PMID- 24720971
TI  - HPLC-ED of low-molecular weight brominated phenols and tetrabromobisphenol A
      using pretreated carbon fiber microelectrode.
AB  - Electrochemically pretreated carbon fiber microelectrode was used to develop a
      simple, fast and sensitive HPLC-ECD method for the determination of brominated
      phenols. In addition to simple mono-, di- and tri-bromophenols (4-bromophenol,
      2,4-dibromophenol, 2,6-dibromophenol, 2,4,6-tri-bromophenol) the possibility of
      electrochemical detection of 3,3',5,5'-tetrabromobisphenol A in oxidation mode is
      reported for the first time. The isocratic separation was achieved within 14 min
      using ternary mobile phase consisting of 50mM-phosphate buffer (pH 3.5),
      acetonitrile and methanol (35/15/50, v/v), and detection potential of E=+1450 mV
      (vs. Ag/AgCl). The carbon fiber microelectrode permitted to use high anodic
      potentials (up to +1800 mV vs. Ag/AgCl), the optimum analytical response was
      achieved at +1450 mV vs. Ag/AgCl. The limits of detection (LOD) for the studied
      analytes were within the range of 1.8-56.6 ng mL(-1). The developed method was
      applied to determination of brominated phenols in spiked water samples.
      Furthermore, after simple extraction with methyl tert-butyl ether, it was
      possible to quantify tetrabromobisphenol A (TBBA) in a piece of CRT monitor
      plastic casing. The found amount of TBBA was 10.22 mg kg(-1) (+/-0.43).

PMID- 24720972
TI  - Kinetic performance comparison of fully and superficially porous particles with a
      particle size of 5 um: intrinsic evaluation and application to the impurity
      analysis of griseofulvin.
AB  - After the great commercial success of sub-3 um superficially porous particles,
      vendors are now also starting to commercialize 5 um superficially porous
      particles, as an alternative to their fully porous counterparts which are
      routinely used in pharmaceutical analysis. In this study, the performance of 5 um
      superficially porous particles was compared to that of fully porous 5 um
      particles in terms of efficiency, separation performance and loadability on a
      conventional HPLC instrument. Van Deemter and kinetic plots were first used to
      evaluate the efficiency and performance of both particle types using
      alkylphenones as a test mixture. The van Deemter and kinetic plots showed that
      the superficially porous particles provide a superior kinetic performance
      compared to the fully porous particles over the entire relevant range of
      separation conditions, when both support types were evaluated at the same
      operating pressure. The same observations were made both for isocratic and
      gradient analysis. The superior performance was further demonstrated for the
      separation of a pharmaceutical compound (griseofulvin) and its impurities, where
      a gain in analysis time of around 2 could be obtained using the superficially
      porous particles. Finally, both particle types were evaluated in terms of
      loadability by plotting the resolution of the active pharmaceutical ingredient
      and its closest impurity as a function of the signal-to-noise ratio obtained for
      the smallest impurity. It was demonstrated that the superficially porous
      particles show better separation performance for griseofulvin and its impurities
      without significantly compromising sensitivity due to loadability issues in
      comparison with their fully porous counterparts. Moreover these columns can be
      used on conventional equipment without modifications to obtain a significant
      improvement in analysis time.

PMID- 24720973
TI  - Anodic electrochemiluminescence of graphitic-phase C3N4 nanosheets for sensitive
      biosensing.
AB  - This work observed the anodic electrochemiluminescence (ECL) of C3N4 nanosheets
      (CNNS) for the first time. The ECL emission was 40 times stronger than that from
      bulk g-C3N4 in the presence of triethylamine (Et3N) as a coreactant due to large
      surface-to-volume ratio, which enhanced the sensitivity for biosensing. At pH
      7.0, the CNNS modified electrode prepared with 0.75 mg mL(-1) CNNS in 0.025%
      chitosan solution possesses good stability and acceptable reproducibility in the
      presence of 30 mM Et3N. The ECL mechanism of CNNS/Et3N system was proposed to be
      emitted from the excited CNNS, which was produced during the reaction between the
      electro-oxidation products of CNNS and coreactant Et3N. Based on the annihilation
      between the oxidation product of dopamine (DA(+)) and Et3N radical, a quenching
      based method was established for sensitive and specific detection of dopamine
      ranging from 1.0 nM to 100 nM with a detection limit of 96 pM by using the CNNS
      nanosheets as an ECL emitter. The proposed method showed excellent specificity,
      high sensitivity and low detection limit, and could be applied in analysis of
      real samples.

PMID- 24720974
TI  - A competitive electrochemical immunosensor for the detection of human interleukin
      6 based on the electrically heated carbon electrode and silver nanoparticles
      functionalized labels.
AB  - A facile one-step electrochemical reduction method was developed to prepare
      electrochemically reduced graphene oxide (ERGO) and gold-palladium bimetallic
      nanoparticles (AuPdNPs) as the platform of immunosensor. A novel competitive
      electrochemical immunosensor was then proposed by combining the ERGO-AuPdNPs
      platform with silver nanoparticles (AgNPs) functionalized polystyrene
      bionanolabel for the sensitive detection of human interleukin-6 (IL-6). An
      electrically heated carbon electrode (HCPE) was introduced in the detection
      procedure of the immunosensor, and further improved the sensitivity. The
      immunosensor exhibited a wide linear response to IL-6 ranging from 0.1 to 100000
      pg mL(-1) with a detection limit of 0.059 pg mL(-1). The proposed method showed
      good precision, broad linear range, acceptable stability and high
      reproducibility, and could be used for the detection of IL-6 in real samples,
      which possessed promising application in clinical research.

PMID- 24720975
TI  - Tannic acid functionalized N-doped graphene modified glassy carbon electrode for
      the determination of bisphenol A in food package.
AB  - A rapid, environmental friendly, and sensitive sensor for the detection of
      bisphenol A (BPA) was developed at glassy carbon electrode (GCE) modified with
      Tannic acid functionalized N-doped graphene (TA/N-G) immobilized by Nafion.
      Compared with other sensors, the proposed sensor greatly enhanced the response
      signal of BPA due to the active surface area of N-G and high absorption
      efficiency of TA. Under the optimal conditions, the oxidation current increased
      linearly with increasing the concentration of BPA in the range of 0.05-13 uM with
      the detection limit of 4.0 nM. The fabricated electrode showed good
      reproducibility, stability and anti-interference. The developed electrochemical
      sensor was successfully applied to determine BPA in food package.

PMID- 24720976
TI  - A novel method for evaluating flavanols in grape seeds by near infrared
      hyperspectral imaging.
AB  - Chemical composition of seeds changes during grape ripening and this affects the
      sensory properties of wine. In order to control the features of wines, the
      condition of seeds is becoming an important factor for deciding the moment of
      harvesting by winemakers. Sensory analysis is not easy to carry out and chemical
      analysis needs lengthy procedures, reagents, and it is destructive and time
      consuming. In the present work, near infrared hyperspectral imaging has been used
      to determine flavanols in seeds of red (cv. Tempranillo) and white (cv. Zalema)
      grapes (Vitis vinifera L.). As reference measurements, the flavanol content was
      estimated using the p-dimethylaminocinnamaldehyde (DMACA) method. Not only total
      flavanol content was evaluated but also the quantity of flavanols that would be
      extracted into the wine during winemaking. A like-wine model solution was used
      for this purpose. Calibrations were performed by partial least squares regression
      and they provide coefficients of determination R(2)=0.73 for total flavanol
      content and R(2)=0.85 for predicting flavanols extracted with model solution.
      Values up to R(2)=0.88 were reached when cultivars were considered individually. 

PMID- 24720977
TI  - Sorption effects interfering with the analysis of polycyclic aromatic
      hydrocarbons (PAH) in aqueous samples.
AB  - Polycyclic aromatic hydrocarbons (PAH) are severe environmental pollutants that
      are analyzed frequently. The risk assessment of PAH impact to groundwater can be
      performed using leaching tests. Therby a liquid-solid separation step including
      centrifugation may be required, which in turn might lead to loss of analytes due
      to sorption on the equipment. Thus we determined the PAH recoveries from various
      container materials (polyethylene (PE), polypropylene (PP),
      polytetraflourethylene (PTFE), stainless steel (ES), and perflouroalkoxy (PFA))
      and compared them to selected PAH properties. We found the best recoveries for
      PFA (68%) and PTFE (65%) containers. We found good negative correlations (-0.93
      and better) between PAH recovery and log partition coefficient organic carbon
      water (logKOC) for PFA, PTFE, and ES containers. 

PMID- 24720978
TI  - Fluorescence enhancement of CdTe MPA-capped quantum dots by glutathione for
      hydrogen peroxide determination.
AB  - The manipulation of the surface chemistry of semiconductor nanocrystals has been
      exploited to implement distinct sensing strategies in many analytical
      applications. In this work, reduced glutathione (GSH) was added at reaction time,
      as an electron-donor ligand, to markedly increase the quantum yield and the
      emission efficiency of MPA-capped CdTe quantum dots. The developed approach was
      employed in the implementation of an automated flow methodology for hydrogen
      peroxide determination, as this can oxidize GSH preventing its surface
      passivating effect and producing a manifest fluorescence quenching. After
      optimization, linear working calibration curve for hydrogen peroxide
      concentrations between 0.0025% and 0.040% were obtained (n=6), with a correlation
      coefficient of 0.9975. The detection limit was approximately 0.0012%. The
      developed approach was employed in the determination of H2O2 in contact lens
      preservation solutions and the obtained results complied with those furnished by
      the reference method, with relative deviations comprised between -1.18 and 4.81%.

PMID- 24720979
TI  - SPR bacterial pathogen biosensor: the importance of fluidic conditions and
      probing depth.
AB  - The sensitivity of surface plasmon resonance (SPR) biosensor technology for
      detection of bacterial analytes is investigated as a function of (a) sample flow
      conditions and (b) depth of probing electromagnetic field. These parameters are
      extremely important as such analytes exhibit large (of around micrometer) size
      which significantly hinders their diffusion-driven transfer from a liquid sample
      to the sensor and their subsequent specific capture by attached recognition
      elements. This is due to small diffusion coefficient and strong shear stress that
      decreases the stability of bonds between the bacterium specific epitope and
      recognition elements immobilized at the sensor surface. The importance of
      accurate control of sample flow conditions and probing depth in order to maximize
      SPR sensor response is experimentally demonstrated and supported by an analytical
      theory. The tuning of the probing depth of surface plasmon evanescent field to
      match the size of the target analyte is pursued by using long range surface
      plasmons. 

PMID- 24720980
TI  - Lipophilicity indices derived from the liquid chromatographic behavior observed
      under bimodal retention conditions (reversed phase/hydrophilic interaction):
      application to a representative set of pyridinium oximes.
AB  - The liquid chromatographic behavior observed under bimodal retention conditions
      (reversed phase and hydrophilic interaction) offers a new basis for the
      determination of some derived lipophilicity indices. The experiments were carried
      out on a representative group (30 compounds) of pyridinium oximes,
      therapeutically tested in acetylcholinesterase reactivation, covering a large
      range of lipophilic character. The chromatographic behavior was observed on a
      mixed mode acting stationary phase, resulting from covalent functionalization of
      high purity spherical silica with long chain alkyl groups terminated by a polar
      environment created through the vicinal diol substitution at the lasting carbon
      atoms (Acclaim Mixed Mode HILIC 1 column). Elution was achieved by combining
      different proportions of 5 mM ammonium formiate solutions in water and
      acetonitrile. The derived lipophilicity indices were compared with logP values
      resulting from different computational algorithms. The correlations between
      experimental and computed data sets are significant. To obtain a better insight
      on the transition from reversed phase to hydrophilic interaction retention
      mechanisms, the variation of the thermodynamic parameters determined through the
      van't Hoff approach was also discussed.

PMID- 24720981
TI  - Comparison of monolithic capillary electrochromatography and micellar
      electrokinetic chromatography for the separation of polycyclic aromatic
      hydrocarbons.
AB  - Atmospheric pollution of anthropic origin is recognized as a major risk factor
      for health, in particular for respiratory and cardio-vascular systems. Among
      these pollutants, polycyclic aromatic hydrocarbons (PAHs) are placed on the list
      of US Environmental Protection Agency (EPA) as 'priority' pollutants and four of
      them are assigned as potential carcinogens by The International Agency for
      Research on Cancer (IARC). In the present work two capillary techniques-micellar
      electrokinetic chromatography (MEKC) and monolithic capillary
      electrochromatography (CEC)-were compared for the separation of eleven PAHs. Both
      techniques compared in the present work are fully compatible with every standard
      apparatus of capillary electrophoresis. For MEKC, enhancement of selectivity and
      decrease of the separation window of eleven PAHs were obtained with
      methanol:borate 25 mM (20/80, v/v) running buffer containing 10 mM of
      hydroxypropylated gamma-cyclodextrins with low SDS content (25 mM). In case of
      CEC, two acrylate-based monolithic stationary phases (MSPs) were evaluated for
      their application in the separation of eleven PAHs. The best MSP based on butyl
      acrylate was compared with MEKC in terms of sample capacity, PAHs elution order,
      LOQ, efficiency and effect of pH. Influence of the hydrophobicity of mobile phase
      on the PAHs elution order was also studied.

PMID- 24720982
TI  - Multi-walled carbon nanotubes/Nafion composite film modified electrode as a
      sensor for simultaneous determination of ondansetron and morphine.
AB  - The electrochemical behavior of ondansetron was studied on the multi-walled
      carbon nanotubes/Nafion polymer composite modified glassy carbon electrode
      (MWCNTs-Nafion/GCE). The oxidation peak potential was shifted from 1.32 V to 1.18
      V compared to the bare electrode indicating excellent electrocatalytic activity
      of immobilized film toward drug molecule. The modified electrode exhibited a
      remarkable enhancement effect on voltammetric response due to the synergistic
      effect of nanomaterial and cation-exchange polymer on the electron transfer rate,
      the effective electrode area and the accumulation capability. After optimizing
      the experimental parameters, adsorptive stripping procedure was used for the
      determination of ondansetron in pharmaceutical formulation. The results were
      satisfactory in comparison with those obtained by high-performance liquid
      chromatography. In addition, the MWCNTs-Nafion/GCE exhibited high selectivity in
      the voltammetric measurements of ondansetron and co-administrated drug morphine
      with potential difference of 430 mV. The response peak currents had linear
      relationship with drug concentration in the range of 1.0 * 10(-7)-5.0 * 10(-6)M
      and 1.0 * 10(-7)-4.0 * 10(-6)M with detection limits 3.1 * 10(-8) and 3.2 * 10(
      8)M for ondansetron and morphine, respectively. The electrode was successfully
      applied for simultaneous electrochemical sensing of both drugs in human serum
      samples after selective accumulation at the electrode surface.

PMID- 24720983
TI  - Fabrication of multiwalled carbon nanotubes-magnetite nanocomposite as an
      effective ultra-sensing platform for the early screening of nasopharyngeal
      carcinoma by luminescence immunoassay.
AB  - The hybrid nanocomposite that consists of multiwalled carbon nanotubes (MWCNTs)
      and magnetite (Fe3O4) was fabricated by chemical co-precipitation method.
      Briefly, CNTs were oxidized with acids to form carboxylic group and then co
      precipitated with Fe3O4 to form CNT-Fe3O4 nanocomposites. The nanocomposites were
      characterized by SEM, HRTEM, XRD, FTIR X-ray photoelectron spectrometry (XPS) and
      SQUID. The XRD results indicated the high crystallinity of Fe3O4 nanoparticles
      with spinel structure and the transmission electron microscope images depicted
      the intercalated iron oxide magnetic particles on the surface of CNTs. The MWCNTs
      Fe3O4 was applied as a sensing interface to perform luminescence enzyme
      immunoassays. Firstly, EBNA-1 antigen was immobilized onto the carboxyl group
      functionalized MWCNTs-Fe3O4, followed by binding with anti-EBNA-1 IgA antibodies.
      The diluted secondary antibodies (anti-human IgA-HRP) were then added to the
      CNTs/Fe3O4-PEG-EBNA-1-anti-EBV IgA ab complex and act as a catalyst to produce a
      visible light upon reaction with the substrate luminol. The formed RLU is
      proportional to the amount of IgA anti-EBV antiobodies on the MWCNTs. The
      detection limit of proposed CNTs/Fe3O4 based luminescence enzyme immunoassay was
      in the order of 0.00128 EU/mL (1:100,000 fold dilution) for the detection of anti
      EBV IgA antibodies, whereas the commercial ELISA and magnetic beads' assay was
      accounted for up to the dilution fold of 1000 (i.e., 0.128 EU/mL). The initial
      findings showed that CNTs/Fe3O4 nanocomposites have a great potential in
      luminescent enzyme immunoassays and could be used as a sensing platform for the
      early screening of nasopharyngeal carcinoma.

PMID- 24720984
TI  - H2 sensing properties of two-dimensional zinc oxide nanostructures.
AB  - In this work we have grown particular zinc oxide two-dimensional nanostructures
      which are essentially a series of hexagonal very thin sheets. The hexagonal
      wurtzite crystal structure gives them their peculiar shape, whose dimensions are
      few microns wide, with a thickness in the order of 25 nm. Such kind of
      nanostructure, grown by thermal oxidation of evaporated metallic zinc on a silica
      substrate, has been used to fabricate conductometric gas sensors, investigated
      then for hydrogen gas detection. The "depletion layer sensing mechanism" is
      clarified, explaining how the geometrical factors of one- and two-dimensional
      nanostructures affect their sensing parameters. The comparison with one
      dimensional ZnO nanowires based structures shows that two-dimensional
      nanostructures are ideal for gas sensing, due to their tiny thickness, which is
      comparable to the depletion-layer thickness, and their large cross-section, which
      increases the base current, thus lowering the limit of detection. The response to
      H2 has been found good even to sub-ppm concentrations, with response and recovery
      times shorter than 18s in the whole range of H2 concentrations investigated (500
      ppb-10 ppm). The limit of detection has been found around 200 ppb for H2 gas even
      at relatively low working temperature (175  degrees C).

PMID- 24720985
TI  - Determination of UV active inorganic anions in potable and high salinity water by
      ion pair reversed phase liquid chromatography.
AB  - Reversed phase column was dynamically modified into anion exchange column using
      various types of tetraalkylammonium salts as ion pair reagents (IPRs) for the
      separation and quantification of toxic anions such as nitrite, bromate, bromide
      and nitrate in potable and high salinity water. Various chromatographic
      parameters such as types and concentration of IPRs, concentration of organic
      modifier, phosphate buffer and mobile phase pH were optimized for the base-line
      separation of anions. The lowest detection limits (LDLs) were 0.2 for nitrate and
      nitrite, 0.6 ug ml(-1)for bromate and bromide respectively for potable water
      samples. NaCl and Na2SO4 were incorporated in the mobile phase for the analysis
      of high salinity water samples to minimize matrix interferences. This has
      resulted in change in elution order of anions, better tolerance of matrix anions
      such as chloride and sulphate. The developed method was successfully utilized for
      analysis of anions in potable, high salinity and sea water samples.

PMID- 24720986
TI  - Application of chemiluminescence in the analysis of wastewaters - a review.
AB  - The toxicological effects of diverse pollutants typically found on wastewaters of
      diverse origin (industrial, urban, etc.) have led to regulation of their emission
      by national and trans-national organizations, and an increasing interest in the
      development of fast and reliable methods for their analysis. This paper is an up
      to-date comprehensive review on the analytical applications of chemiluminescence
      technique (characterized by high sensitivity, wide dynamic ranges and simple
      instrumentation) to the analysis of wastewaters, emphasizing the different kinds
      of pollutants that have been studied with these methods and discussing the
      different approaches followed by the authors as CL reactions, devices and coupled
      methods. 

PMID- 24720987
TI  - Spectra resolution for simultaneous spectrophotometric determination of
      lamivudine and zidovudine components in pharmaceutical formulation of human
      immunodeficiency virus drug based on using continuous wavelet transform and
      derivative transform techniques.
AB  - In the present paper, two spectrophotometric methods based on signal processing
      are proposed for the simultaneous determination of two components of an anti-HIV
      drug called lamivudine (LMV) and zidovudine (ZDV). The proposed methods are
      applied to synthetic binary mixtures and commercial pharmaceutical tablets
      without the need for any chemical separation procedures. The developed methods
      are based on the application of Continuous Wavelet Transform (CWT) and Derivative
      Spectrophotometry (DS) combined with the zero cross point technique. The
      Daubechies (db5) wavelet family (242 nm) and Dmey wavelet family (236 nm) were
      found to give the best results under optimum conditions for simultaneous analysis
      of lamivudine and zidovudine, respectively. In addition, the first derivative
      absorption spectra were selected for the determination of lamivudine and
      zidovudine at 266 nm and 248 nm, respectively. Assaying various synthetic
      mixtures of the components validated the presented methods. Mean recovery values
      were found to be between 100.31% and 100.2% for CWT and 99.42% and 97.37% for DS,
      respectively for determination of LMV and ZDV. The results obtained from
      analyzing the real samples by the proposed methods were compared to the HPLC
      reference method. One-way ANOVA test at 95% confidence level was applied to the
      results. The statistical data from comparing the proposed methods with the
      reference method showed no significant differences.

PMID- 24720988
TI  - Eu(III)-induced room-temperature fast transformation of CdTe nanocrystals into
      nanorods.
AB  - A fast and mild synthesis method of highly crystalline CdTe nanorods (NRs) was
      developed by adding europium nitrate hexahydrate to an aqueous solution of CdTe
      nanocrystals (NCs) at room temperature within 30 min. It was suggested that
      strong coordination strength of Eu(III) decreases zeta potential, thereby
      accelerates aggregation of NCs, and favors the transformation process from NCs to
      NRs. The oriented attachment of aggregated particles was suggested as a major
      path for the formation of highly crystalline NRs under experimental conditions.
      The proposed extremely fast room-temperature methodology opens up novel pathways
      for the synthesis of one-dimensional (1D) semiconductor nanostructures with high
      crystallinity, which would become potential candidates for many practical
      applications such as photovoltaics, circuit design and fabrication of functional
      architectures.

PMID- 24720989
TI  - Evaluation of a new dielectric barrier discharge excitation source for the
      determination of arsenic with atomic emission spectrometry.
AB  - A low power dielectric barrier discharge excitation source was developed to
      determine arsenic in a cost-effective manner. Arsenic in water was reduced to
      AsH3 by hydride generation (HG), which was transported to the miniature
      dielectric barrier discharge (DBD) excitation source for excitation and optical
      detection at As 193.7 nm atomic line. The DBD source consists of a quartz tube, a
      tungsten rod electrode, and a copper coil electrode. The main operation
      parameters and the potential interferences affecting the determination were
      investigated. The detection limit for arsenic with the proposed DBD-AES was 4.8
      MUg L(-1) when the HG products were dried with concentrated H2SO4 before
      introducing to DBD. Repeatability, expressed as the relative standard deviation
      of the spectral peak height, was 2.8% (n=11) for 0.1 mg L(-1) arsenic solution.
      The proposed method was successfully applied to the determinations of certified
      reference material (GBW08605) and nature water samples.

PMID- 24720990
TI  - Speciation of arsenic in a thermoacidophilic iron-oxidizing archaeon, Acidianus
      brierleyi, and its culture medium by inductively coupled plasma-optical emission
      spectroscopy combined with flow injection pretreatment using an anion-exchange
      mini-column.
AB  - The thermoacidophilic iron-oxidizing archaeon Acidianus brierleyi is a
      microorganism that could be useful in the removal of inorganic As from
      wastewater, because it simultaneously oxidizes As(III) and Fe(II) to As(V) and
      Fe(III) in an acidic culture medium, resulting in the immobilization of As(V) as
      FeAsO4. To investigate the oxidation mechanism, speciation of the As species in
      both the cells and its culture media is an important issue. Here we describe the
      successive determination of As(III), As(V), and total As in A. brierleyi and its
      culture medium via a facile method based on inductively coupled plasma-optical
      emission spectroscopy (ICP-OES) with a flow injection pretreatment system using a
      mini-column packed with an anion-exchange resin. The flow-injection pretreatment
      system consisted of a syringe pump, a selection valve, and a switching valve,
      which were controlled by a personal computer. Sample solutions with the pH
      adjusted to 5 were flowed into the mini-column to retain the anionic As(V),
      whereas As(III) was introduced into ICP-OES with no adsorption on the mini-column
      due to its electrically neutral form. An acidic solution (1 M HNO3) was then
      flowed into the mini-column to elute As(V) followed by ICP-OES measurement. The
      same sample was also subjected to ICP-OES without being passed through the mini
      column in order to determine the total amounts of As(III) and As(V). The method
      was verified by comparing the results of the total As with the sum of As(III) and
      As(V). The calibration curves showed good linearity with limits of detection of
      158, 86, and 211 ppb for As(III), As(V), and total As, respectively. The method
      was successfully applicable to the determination of the As species contained in
      the pellets of A. brierleyi and their culture media. The results suggested that
      the oxidation of As(III) was influenced by the presence of Fe(II) in the culture
      medium, i.e., Fe(II) enhanced the oxidation of As(III) in A. brierleyi. In
      addition, we found that no soluble As species was contained in the cell pellets
      and more than 60% of the As(III) in the culture medium was oxidized by A.
      brierleyi after a 6-day incubation.

PMID- 24720991
TI  - Microfluidic chip integrating high throughput continuous-flow PCR and DNA
      hybridization for bacteria analysis.
AB  - Rapid identification of clinical pathogens is the initial and essential step for
      antimicrobial therapy. Herein, we successfully developed a microfluidic device
      which combines high-throughput continuous-flow PCR and DNA hybridization for the
      detection of various bacterial pathogens. Universal primers were designed based
      on the conserved regions of bacterial 16S ribosomal DNA (16S rDNA), and specific
      probes were designed from a variable region of 16S rDNA within the amplicon
      sequences. In the chip operation, after the continuous flow PCR was achieved in
      the first microfluidic chip, the product was directly introduced into a
      hybridization chip integrated with microarray containing the immobilized DNA
      probes. The target-probe hybridization was completed within 1h at 55  degrees C,
      and fluorescence signals were obtained as the readout. The presented device is
      simple, versatile and with less sample consumption compared with traditional
      instruments. It can perform high-throughput bacteria detections continuously in a
      single assay, which makes it a promising platform for clinical bacteria
      identifications.

PMID- 24720992
TI  - An optical sensor for pesticide determination based on the autoindicating optical
      properties of peroxidase.
AB  - During the enzymatic reaction of the heme-protein Horseradish peroxidase (HRP)
      with hydrogen peroxide there are changes in the molecular absorption spectra of
      HRP and its different oxidation states which can be used for quantitative
      determination of the substrate. One of these intermediate oxidation states is the
      HRPII, with iron as an oxyferryl. This compound is assumed to be responsible for
      the organophosphate pesticide degradation in the Fenton reaction. In this work,
      the enzymatic HRP-H2O2 reaction has been studied, based on the effect of
      different pesticides on the mechanism reaction; these modifications have been
      used for the quantitative determination of pesticides. A mathematical model has
      been developed relating to the analytical signal with the pesticide
      concentration. Three organophosphate pesticides (diazinon, trichlorfon and
      tetrachlorvinphos) and one sulfamide (dichlofluanid) have been used to
      demonstrate the viability of the methodology and the accomplishment fulfillment
      of the model. Tetrachlorvinphos was chosen as the pesticide model to develop the
      optical sensor film for continuous pesticide determination, consisting of HRP
      immobilized in a polyacrylamide gel. The sensor can be used for at least 15 days
      and responds linearly to tetrachlorvinphos concentrations in the range from 4.0 *
      10(-7) to 4.0 * 10(-6)mol L(-1). The main advantage of the methodology is its
      reversibility in contrast to the irreversible Fenton reaction. The HRP-H2O2
      methodology has been used to measure the pesticides in a waste water sample
      spiked with tetrachlorvinphos.

PMID- 24720993
TI  - An automated sequential injection spectrophotometric method for evaluation of
      tyramine oxidase inhibitory activity of some flavonoids.
AB  - An automated sequential injection (SI) spectrophotometric system has been
      developed for evaluation of tyramine oxidase (TOD) inhibitory activity. The
      method is based on the inhibition of TOD that catalyzes the oxidation of tyramine
      substrate to produce aldehyde and hydrogen peroxide (H2O2). The produced H2O2
      reacts with vanillic acid and 4-aminoantipyrine (4-AA) in the presence of
      peroxidase (POD) to form a quinoneimine dye, the absorbance of which is measured
      of absorbance at wavelength of 490 nm. The decrease of the quinoneimine dye is
      related to an increase of TOD inhibitory activity. Under the optimum conditions:
      1.0 mM tyramine, 8 U mL(-1) TOD, 1.0 mM vanillic acid, 1.0 mM 4-AA and delay time
      of 10 s, some flavonoid compounds were examined for the TOD inhibitory activity
      expressed as IC50 value. It was found that flavonols (quercetin and myricetin)
      and flavans (epicatechin gallate (ECG) and epigallocatechin (EGC)) showed higher
      TOD inhibitory activity than flavones and flavanones. The results of IC50 values
      obtained from the proposed method and a batch-wise method were not significantly
      different from each other. Moreover, the SI system enabled automation of the
      analysis, leading to more convenient, more sensitive and faster analysis than the
      batch-wise method. A precise timing of the system also improves precision and
      accuracy of the assay, especially when the measurement of absorbance at non
      steady state condition is involved.

PMID- 24720994
TI  - Evaluation of polyethersulfone performance for the microextraction of polar
      chlorinated herbicides from environmental water samples.
AB  - In this work, the suitability of bulk polyethersulfone (PES) for sorptive
      microextraction of eight polar, chlorinated phenoxy acids and dicamba from
      environmental water samples is assessed and the analytical features of the
      optimized method are compared to those reported for other microextraction
      techniques. Under optimized conditions, extractions were performed with samples
      (18 mL) adjusted at pH 2 and containing a 30% (w/v) of sodium chloride, using a
      tubular PES sorbent (1 cm length * 0.7 mm o.d., sorbent volume 8 uL). Equilibrium
      conditions were achieved after 3h of direct sampling, with absolute extraction
      efficiencies ranging from 39 to 66%, depending on the compound. Analytes were
      recovered soaking the polymer with 0.1 mL of ethyl acetate, derivatized and
      determined by gas chromatography-mass spectrometry (GC-MS). Achieved
      quantification limits (LOQs) varied between 0.005 and 0.073 ng mL(-1). After
      normalization with the internal surrogate (IS), the efficiency of the extraction
      was only moderately affected by the particular characteristics of different water
      samples (surface and sewage water); thus, pseudo-external calibration, using
      spiked ultrapure water solutions, can be used as quantification technique. The
      reduced cost of the PES polymer allowed considering it as a disposable sorbent,
      avoiding variations in the performance of the extraction due to cross
      contamination problems and/or surface modification with usage.

PMID- 24720995
TI  - A new rapid colorimetric detection method of Al3+ with high sensitivity and
      excellent selectivity based on a new mechanism of aggregation of smaller etched
      silver nanoparticles.
AB  - As a pathogenic factor of the Alzheimer's disease, aluminum has been associated
      with the damage of the central nervous system in humans. In this study, we
      propose a new facile and rapid colorimetric detection method of Al(3+) with
      excellent selectivity and high sensitivity based on silver nanoparticles (AgNPs)
      stabilized by reduced glutathione (GSH) in the presence of l-cysteine (Cys). The
      new mechanism of our Al(3+) detection system based on GSH-AgNPs, i.e.,
      aggregation of smaller etched GSH-AgNPs, are confirmed by TEM, EDS and DLS. The
      aggregation of smaller etched GSH-AgNPs results in obvious color change of the
      nanoparticle dispersion from yellow to reddish brown, and red shift and intensity
      decrease of the surface plasmon resonance (SPR) absorption. The GSH
      concentration, Cys concentration and pH value of the GSH-AgNPRs-based detection
      system are respectively optimized to be 10.0 mM, 50.0 mM and 6.0 according to the
      sensing effect of Al(3+). At the optimized conditions, the selectivity of the GSH
      AgNPs detection system for Al(3+) is excellent compared with other ions including
      K(+), Mg(2+), Fe(3+), Co(2+), Mn(2+), Zn(2+), Cd(2+), Pb(2+), Ca(2+), Ba(2+),
      Cu(2+), Cr(3+), Hg(2+), Ni(2+), [Formula: see text] , [Formula: see text] ,
      [Formula: see text] , [Formula: see text] and [Formula: see text] . Furthermore,
      this detection system is very sensitive for Al(3+). The limit of detection (LOD)
      is 1.2 uM by the naked eyes and 0.16 uM by UV-vis spectra, which are both much
      lower than the national drinking water standards (7.4 uM). Furthermore, the UV
      vis detection offers a good linear detection range from 0.4 to 4.0 uM
      (R(2)=0.9924), which indicates that our developed detection system can also be
      used for the quantitative analysis of Al(3+). The detection results of real water
      samples indicate that this method can be used for real water detection.

PMID- 24720996
TI  - Dendrimer-grafted graphene oxide nanosheets as novel support for trypsin
      immobilization to achieve fast on-plate digestion of proteins.
AB  - In this study, dendrimer grafted graphene oxide nanosheets (dGO) were prepared by
      covalent reaction. The successful synthesis of dGO was confirmed by Fourier
      transform infrared spectra, Raman spectra, Thermo gravimetric analysis and Zeta
      potential. Taking advantages of large surface area, excellent biocompatibility
      and abundant functional groups, dGO provided an ideal substrate for trypsin
      immobilization. Trypsin-linked dGO was synthesized through covalent bonding using
      glutaraldehyde as coupling agents. The amount of trypsin immobilized on dGO
      nanosheets was calculated to be about 649 +/- 20 mg/g. The activity of
      immobilized trypsin could be maintained for over 10 days at 4  degrees C. On
      plate proteolysis could be performed without removing trypsin-linked dGO, because
      dGO did not interfere with matrix-assisted laser desorption ionization time-of
      flight tandem mass spectrometry analysis. By such an immobilized enzymatic
      reactor, standard proteins could be efficiently digested within 15 min, with
      sequence coverages comparable or better than those obtained by conventional over
      night in-solution digestion. Furthermore, trypsin-linked dGO showed high
      sensitivity when applied to trace samples analysis. All these results
      demonstrated that the developed dGO based enzymatic reactor might provide a
      promising tool for high throughput proteome identification.

PMID- 24720997
TI  - Square wave anodic stripping voltammetric determination of Cd2+ and Pb2+ at
      bismuth-film electrode modified with electroreduced graphene oxide-supported
      thiolated thionine.
AB  - Graphene oxide (GO)-thionine (TH) nanocomposite was prepared by pi-pi stacking.
      The nanocomposite was cast-coated on a glassy carbon electrode (GCE) to prepare
      an electroreduced GO (ERGO)-TH/GCE, then 2-mercaptoethanesulfonate (MES) was
      covalently tethered to ERGO-TH by potentiostatic anodization to form an ERGO-TH
      MES/GCE. The thiolation reaction was monitored by electrochemical quartz crystal
      microbalance (EQCM). Square wave anodic stripping voltammetry (SWASV) was used to
      determine Cd(2+) and Pb(2+) at the ERGO-TH-MES/GCE further modified with Nafion
      and Bi. Under the optimal conditions, the linear calibration curves for Cd(2+)
      and Pb(2+) are from 1 to 40 MUg L(-1), with limits of detection (S/N=3) of 0.1
      MUg L(-1) for Cd(2+) and 0.05 MUg L(-1) for Pb(2+), respectively. The electrode
      was used for the simultaneous analysis of Cd(2+) and Pb(2+) in water samples with
      satisfactory recovery.

PMID- 24720998
TI  - Direct quantitative analysis of aromatic amino acids in human plasma by four-way
      calibration using intrinsic fluorescence: exploration of third-order advantages.
AB  - A novel intrinsic fluorescence method for the direct determination of l
      phenylalanine, l-tyrosine, and l-tryptophan in human plasma is presented. By
      using fluorescence excitation-emission-pH-sample data array in combination with
      four-way calibration method based on the quadrilinear component model, the
      proposed approach successfully achieved quantitative analysis of the aromatic
      amino acids in human plasma, even in the presence of an unknown, uncalibrated
      serious interferent. It needs little preparation, uses the "mathematical
      separation" instead of "analytical separation", what makes it fast and
      environmentally friendly. Satisfactory results have been achieved for calibration
      set, validation set, and prediction set. The ranges for phenylalanine, tyrosine,
      and tryptophan are 2.0 * 10(3)-20.0 * 10(3), 50.0-500.0, and 20.0-200.0 ng mL(-1)
      respectively. Average spike recoveries (mean +/- standard deviation) are 93.3 +/-
      7.7%, 104.3 +/- 6.6%, and 99.5 +/- 9.0% respectively. The real concentrations in
      human plasma are 10.2 +/- 0.3, 6.6 +/- 0.1, and 5.3 +/- 0.1 MUg mL(-1)
      respectively, which are consistent with the results obtained by LC-MS/MS method
      and reference values. In addition, we explored the third-order advantages through
      the real four-way array; it has shown that higher resolving power is one of the
      main advantages of higher-order tensor calibration method. These results
      demonstrated that the proposed method is sensitive, accurate, and efficient for
      direct quantitative analysis of aromatic amino acids in human plasma.

PMID- 24720999
TI  - [Hypothenar hammer syndrome: case report and review of the literature].
AB  - INTRODUCTION: Hypothenar hammer syndrome is a rare cause of upper extremity
      digital ischemia or Raynaud phenomenon, a diagnosis which should be considered in
      cases of iterative palmar trauma. Its treatment can be medical or surgical and
      should not suffer any delay. The best options remain controversial. METHODS: A 65
      year-old patient presented with an ischemia of the last three fingers of the left
      hand. A partially thrombosed aneurysm of the left ulnar artery was diagnosed at
      imaging. After a partially effective medical treatment, a surgical treatment was
      performed with resection of the aneurysm and a vascular reconstruction with an
      autologous vein graft. The postoperative course was uneventful with disappearance
      of the symptoms and revascularization of the hypothenar area. CONCLUSION:
      Appropriate treatment for hypothenar hammer syndrome is controversial but whould
      always begin with medical care. The decision to perform surgery should be based
      on evidence of ulnar artery lesions and the associated symptoms.

PMID- 24721000
TI  - [Recurrent deep vein thrombosis and myeloproliferative syndrom: emergence of JAK2
      mutation five years after the initial event].
AB  - JAK 2 mutation is the molecular event responsible for 95% of polycythemia cases
      and 50% of thrombocythemia vera and myelofibrosis cases. It can be used as a tool
      for the diagnosis of myeloproliferative disorders. We report a case illustrating
      the fact that a negative result does not definitively eliminate the diagnosis. A
      40-year old woman, with a medical history of familial deep vein thrombosis,
      developed thrombosis of the inferior vena cava with extension to the suprahepatic
      veins and pulmonary embolism. No constitutional or acquired thrombophilia was
      diagnosed; search for JAK 2 mutation was negative. The patient was treated with
      fluindione. Five years later, she relapsed with popliteo-femoral and vena cava
      deep vein thrombosis. The etiological work-up included a PET scan which revealed
      diffuse uptake in bones and suspected neoplasic bone marrow invasion. Progenitor
      cell cultures were positive and JAK 2 mutation was confirmed. The bone marrow
      aspirate had the cytologic appearance of a myeloproliferative disorder. This case
      illustrates the fact that JAK 2 mutation can be identified several years after
      onset of a latent myeloproliferative disorder. Cases with a high clinical
      likelihood should lead to renewed search for this mutation. Secondary discovery
      of this mutation can be explained by a higher proportion of mutation expressing
      clones. 

PMID- 24721001
TI  - Natural variability in species-specific vocalizations constrains behavior and
      neural activity.
AB  - A listener's capacity to discriminate between sounds is related to the amount of
      acoustic variability that exists between these sounds. However, a full
      understanding of how this natural variability impacts neural activity and
      behavior is lacking. Here, we tested monkeys' ability to discriminate between
      different utterances of vocalizations from the same acoustic class (i.e., coos
      and grunts), while neural activity was simultaneously recorded in the
      anterolateral belt region (AL) of the auditory cortex, a brain region that is a
      part of a pathway that mediates auditory perception. Monkeys could discriminate
      between coos better than they could discriminate between grunts. We also found AL
      activity was more informative about different coos than different grunts. This
      difference could be attributed, in part, to our finding that coos had more
      acoustic variability than grunts. Thus, intrinsic acoustic variability
      constrained the discriminability of AL spike trains and the ability of rhesus
      monkeys to discriminate between vocalizations.

PMID- 24721002
TI  - Cerebrovascular reactivity by quantitative magnetic resonance angiography with a
      Co2 challenge. Validation as a new imaging biomarker.
AB  - Assessment of cerebrovascular reactivity (CVR) is essential in cerebrovascular
      diseases, as exhausted CVR may enhance the risk of cerebral ischemic events.
      Transcranial Doppler (TCD) with a vasodilatory stimulus is currently used for CVR
      evaluation. Scanty data are available for Quantitative Magnetic Resonance
      Angiography (QMRA), which supplies higher spatial resolution and quantitative
      cerebral blood flow values. Aims of our pilot study were: (a) to assess safety
      and feasibility of CO2 administration during QMRA, (b) evaluation of CVR under
      QMRA compared to TCD, and (c) quantitative evaluation of blood flow from the
      major intracranial arterial vessels both at rest and after CO2. CVR during 5% CO2
      air breathing was measured with TCD as a reference method and compared with QMRA.
      Fifteen healthy subjects (age 60.47 +/- 2.24; male 11/15) were evaluated at rest
      and during CO2 challenge. Feasibility and safety of QMRA under CO2 were ensured
      in all subjects. CVR from middle cerebral artery territory was not statistically
      different between TCD and MRI (p>0.05). Mean arterial pressure (MAP) and heart
      rate (HR) increased during QMRA and TCD (MAP p=0.007 and p=0.001; HR p=0.043 and
      p=0.068, respectively). Blood flow values from all intracranial vessels increased
      after CO2 inhalation (p<0.001). CO2 administration during QMRA sessions is safe
      and feasible. Good correlation in terms of CVR was obtained comparing TCD and
      QMRA. Blood flow values significantly increased from all intracranial arterial
      vessels after CO2. Studies regarding CVR in physiopathological conditions might
      consider the utilization of QMRA both in routine clinical settings and in
      research projects.

PMID- 24721003
TI  - Paradoxical signal pattern of mediastinal cysts on T2-weighted MR imaging:
      phantom and clinical study.
AB  - PURPOSE: To evaluate the intracystic MRI (magnetic resonance imaging) signal
      intensity of mediastinal cystic masses on T2-weighted images. MATERIALS AND
      METHODS: A phantom study was performed to evaluate the signal intensity of a
      mediastinal cystic mass phantom (rubber balloon containing water) adjacent to a
      cardiac phantom pulsing at the rate of 60/min. T2-weighted images (sequence, fast
      spin echo [FSE] and single shot fast spin echo [SSFSE]) were acquired for the
      mediastinal cystic mass phantom. Further, a clinical study was performed in 33
      patients (16 men, 17 women; age range, 19-85 years; mean, 65 years) with thymic
      cysts or pericardial cysts. In all patients, T2-weighted images (FSE and SSFSE)
      were acquired. The signal intensity of cystic lesion was evaluated and was
      compared with that of muscle. A region of interest (ROI) was positioned on the
      standard MR console, and signal intensity of the cystic mass (cSI), that of the
      muscle (mSI), and the rate of absolute value of cSI-mSI to standard deviation
      (SD) of background noise (|cSI-mSI|/SD=CNR [contrast-to-noise ratio]) were
      measured. RESULTS: The phantom study demonstrated that the rate phantom
      ROI/saline-ROI was higher in SSFSE (0.36) than in FSE (0.19). In clinical cases,
      the degree of the signal intensity was higher in SSFSE than in FSE. The CNR was
      significantly higher in SSFSE (mean +/- standard deviation, 111.0 +/- 47.6) than
      in FSE (72.8 +/- 36.6) (p<0.001, Wilcoxon signed-rank test). CONCLUSIONS:
      Anterior mediastinal cysts often show lower signal intensity than the original
      signal intensity of water on T2-weighted images. SSFSE sequence reduces this
      paradoxical signal pattern on T2-weighted images, which may otherwise cause
      misinterpretation when assessing cystic lesions.

PMID- 24721004
TI  - Primitive polypoid granular-cell tumor.

PMID- 24721005
TI  - MR evaluation of breast lesions obtained by diffusion-weighted imaging with
      background body signal suppression (DWIBS) and correlations with histological
      findings.
AB  - OBJECTIVES: Diffusion imaging represents a new imaging tool for the diagnosis of
      breast cancer. This study aims to investigate the role of diffusion-weighted MRI
      with background body signal suppression (DWIBS) for evaluating breast lesions.
      METHODS: 90 patients were prospectively evaluated by MRI with STIR, TSE-T2,
      contrast enhanced THRIVE-T1 and DWIBS sequences. DWIBS were analyzed searching
      for the presence of breast lesions and calculating the ADC value. ADC values of
      <=1.44*10(-3)mm(2)/s were considered suspicious for malignancy. This analysis was
      then compared with the histological findings. Sensitivity, specificity,
      diagnostic accuracy (DA), positive predictive value (PPV) and negative (NPV) were
      calculated. RESULTS: In 53/90 (59%) patients, DWIBS indicated the presence of
      breast lesions, 16 (30%) with ADC values of >1.44 and 37 (70%) with ADC<=1.44.
      The comparison with histology showed 25 malignant and 28 benign lesions. DWIBS
      sequences obtained sensitivity, specificity, DA, PPV and NPV values of 100, 82,
      87, 68 and 100%, respectively. CONCLUSION: DWIBS can be proposed in the MRI
      breast protocol representing an accurate diagnostic complement.

PMID- 24721006
TI  - A novel approach for fMRI data analysis based on the combination of sparse
      approximation and affinity propagation clustering.
AB  - Clustering analysis has been widely used to detect the functional connectivity
      from functional magnetic resonance imaging (fMRI) data. However, it has some
      limitations such as enormous computer memory requirement, and difficulty in
      estimating the number of clusters. In this study, in order to effectually resolve
      the deficiencies mentioned above, we have proposed a novel approach (SAAPC) for
      fMRI data analysis, which combines sparsity, an effective assumption for
      analyzing fMRI signal, with affinity propagation clustering (APC). The SAAPC
      method is composed of three parts: to obtain the sparse approximation
      coefficients set through wavelet packet decomposition and sparsity measuring and
      selection, which contributes a lot in the brain functional connectivity detection
      accuracy; to implement a split APC algorithm, which is put forward in this paper
      to overcome the computer memory shortage problem and to reduce the time cost in
      basic APC; to reconstruct the source signal by unmixing the mixed fMRI data using
      the time courses which are derived from the ultimate exemplars. In the task
      related experiments, we can see that SAAPC is more accurate to detect the
      functional networks than basic APC, and it significantly reduces the time cost
      relative to basic APC. In addition, in the resting-state data experiments, the
      SAAPC method can successfully identify typical resting-state networks from the
      resting-state data set, while this performance is seldom reported by the
      classical cluster method and the basic APC method. This proposed clustering
      analysis method is expected to have wide applicability. 

PMID- 24721007
TI  - Wireless MR tracking of interventional devices using phase-field dithering and
      projection reconstruction.
AB  - PURPOSE: Device tracking is crucial for interventional MRI (iMRI) because
      conventional device materials do not contribute to the MR signal, may cause
      susceptibility artifacts and are generally invisible if moved out of the scan
      plane. A robust method for wireless tracking and dynamic guidance of
      interventional devices equipped with wirelessly connected resonant circuits (wRC)
      is presented. METHODS: The proposed method uses weak spatially-selective
      excitation pulses with very low flip angle (0.3 degrees ), a Hadamard multiplexed
      tracking scheme and employs phase-field dithering to obtain the 3D position of a
      wRC. RF induced heating experiments (ASTM protocol) and balloon angioplasties of
      the iliac artery were conducted in a perfused vascular phantom and three Thiel
      soft-embalmed human cadavers. RESULTS: Device tip tracking was interleaved with
      various user-selectable fast pulse sequences receiving a geometry update from the
      tracking kernel in less than 30ms. Integrating phase-field dithering
      significantly improved our tracking robustness for catheters with small diameters
      (4-6 French). The volume root mean square distance error was 2.81mm (standard
      deviation: 1.31mm). No significant RF induced heating (<0.6 degrees C) was
      detected during heating experiments. CONCLUSION: This tip tracking approach
      provides flexible, fast and robust feedback loop, intuitive iMRI scanner
      interaction, does not constrain the physician and delivers very low specific
      absorption rates. Devices with wRC can be exchanged during a procedure without
      modifications to the iMRI setup or the pulse sequence. A drawback of our current
      implementation is that position information is available for a single tracking
      coil only. This was satisfactory for balloon angioplasties of the iliac artery,
      but further studies are required for complex navigation and catheter shapes
      before animal trials and clinical application.

PMID- 24721008
TI  - Validity and inter-observer reliability of subjective hand-arm vibration
      assessments.
AB  - Exposure to mechanical vibrations at work (e.g., due to handling powered tools)
      is a potential occupational risk as it may cause upper extremity complaints.
      However, reliable and valid assessment methods for vibration exposure at work are
      lacking. Measuring hand-arm vibration objectively is often difficult and
      expensive, while often used information provided by manufacturers lacks detail.
      Therefore, a subjective hand-arm vibration assessment method was tested on
      validity and inter-observer reliability. In an experimental protocol, sixteen
      tasks handling powered tools were executed by two workers. Hand-arm vibration was
      assessed subjectively by 16 observers according to the proposed subjective
      assessment method. As a gold standard reference, hand-arm vibration was measured
      objectively using a vibration measurement device. Weighted kappa's were
      calculated to assess validity, intra-class-correlation coefficients (ICCs) were
      calculated to assess inter-observer reliability. Inter-observer reliability of
      the subjective assessments depicting the agreement among observers can be
      expressed by an ICC of 0.708 (0.511-0.873). The validity of the subjective
      assessments as compared to the gold-standard reference can be expressed by a
      weighted kappa of 0.535 (0.285-0.785). Besides, the percentage of exact agreement
      of the subjective assessment compared to the objective measurement was relatively
      low (i.e., 52% of all tasks). This study shows that subjectively assessed hand
      arm vibrations are fairly reliable among observers and moderately valid. This
      assessment method is a first attempt to use subjective risk assessments of hand
      arm vibration. Although, this assessment method can benefit from some future
      improvement, it can be of use in future studies and in field-based ergonomic
      assessments. 

PMID- 24721009
TI  - A definition of visual ergonomics.

PMID- 24721010
TI  - Common carotid artery intima-media thickness is useful for diagnosis of the acute
      stage of Kawasaki disease.
AB  - BACKGROUND: This study aimed to investigate intima-media thickness (IMT) of the
      common carotid arteries in children with acute Kawasaki disease (KD). METHODS:
      Between 2009 and 2011, patients fulfilling the criteria for KD, including a fever
      lasting >5 days, were prospectively enrolled in this study. Laboratory data,
      echocardiography, and IMT were measured and compared with matched controls.
      RESULTS: A total of 70 common carotid IMTs were measured in 35 children. We
      studied 21 patients aged 3-60 months old with acute KD and 14 febrile patients
      aged 3-194 months old with acute infection and similar characteristics to those
      of KD patients. Children with KD had a significantly higher IMT compared with the
      controls (0.550 +/- 0.081 mm vs. 0.483 +/- 0.046 mm, P = 0.01). CONCLUSIONS: IMT
      during the acute stage of KD is increased, suggesting that IMT could be a useful
      diagnostic tool in the early diagnosis of KD.

PMID- 24721011
TI  - Isobutanol production at elevated temperatures in thermophilic Geobacillus
      thermoglucosidasius.
AB  - The potential advantages of biological production of chemicals or fuels from
      biomass at high temperatures include reduced enzyme loading for cellulose
      degradation, decreased chance of contamination, and lower product separation
      cost. In general, high temperature production of compounds that are not native to
      the thermophilic hosts is limited by enzyme stability and the lack of suitable
      expression systems. Further complications can arise when the pathway includes a
      volatile intermediate. Here we report the engineering of Geobacillus
      thermoglucosidasius to produce isobutanol at 50 degrees C. We prospected various
      enzymes in the isobutanol synthesis pathway and characterized their
      thermostabilities. We also constructed an expression system based on the lactate
      dehydrogenase promoter from Geobacillus thermodenitrificans. With the best enzyme
      combination and the expression system, 3.3g/l of isobutanol was produced from
      glucose and 0.6g/l of isobutanol from cellobiose in G. thermoglucosidasius within
      48h at 50 degrees C. This is the first demonstration of isobutanol production in
      recombinant bacteria at an elevated temperature. 

PMID- 24721012
TI  - Postural stability in cigarette smokers and during abstinence from alcohol.
AB  - BACKGROUND: Static postural instability is common in alcohol-dependent
      individuals (ALC). Chronic alcohol consumption has deleterious effects on the
      neural and perceptual systems subserving postural stability. However, little is
      known about the effects of chronic cigarette smoking on postural stability and
      its changes during abstinence from alcohol. METHODS: A modified Fregly ataxia
      battery was administered to a total of 115 smoking (sALC) and nonsmoking ALC
      (nsALC) and to 71 smoking (sCON) and nonsmoking light/nondrinking controls
      (nsCON). Subgroups of abstinent ALC were assessed at 3 time points (TPs;
      approximately 1, 5, 34 weeks of abstinence from alcohol); a subset of nsCON was
      retested at 40 weeks. We tested whether cigarette smoking affects postural
      stability in CON and in ALC during extended abstinence from alcohol, and we used
      linear mixed effects modeling to measure change across TPs within ALC. RESULTS:
      Chronic smoking was associated with reduced performance on the Sharpened Romberg
      eyes-closed task in abstinent ALC at all 3 TPs and in CON. The test performance
      of nsALC increased significantly between 1 and 32 weeks of abstinence, whereas
      the corresponding increases for sALC between 1 and 35 weeks were nonsignificant.
      With long-term abstinence from alcohol, nsALC recovered into the range of nsCON
      and sALC recovered into the range of sCON. Static postural stability decreased
      with age and correlated with smoking variables but not with drinking measures.
      CONCLUSIONS: Chronic smoking was associated with reduced static postural
      stability with eyes closed and with lower increases of postural stability during
      abstinence from alcohol. Smoking cessation in alcohol dependence treatment may
      facilitate recovery from static postural instability during abstinence.

PMID- 24721020
TI  - (18)F-FDG PET discovered an elusive cervical inflammatory pseudotumor associated
      with a papillary thyroid cancer.

PMID- 24721021
TI  - Spindle cell oncocytoma of the adenohypophysis: a case report illustrating its
      natural history with 8-year observation and a review of the literature.
AB  - Spindle cell oncocytoma of the adenohypophysis is a rare tumor classified by the
      World Health Organization as benign with no malignant features. Recent
      publications have questioned its identity as a benign tumor, as six postsurgical
      recurrences of spindle cell oncocytoma (SCO) have been reported. This case is the
      first to illustrate the natural history of the disease due to delayed
      intervention, as the tumor showed virtually no growth. This is an important
      illustrative case to highlight that urgent surgery may not be required and
      conservative close serial surveillance MRI may be a valid management option. 

PMID- 24721022
TI  - AFP-producing hepatoid adenocarcinoma of appendix: a case report of 18F-FDG
      PET/CT.
AB  - Hepatoid adenocarcinoma (HAC) is a rare tumor. We described here a rare case of
      appendix HAC. A 59-year-old man underwent F-18-fluorodeoxyglucose (FDG) positron
      emission tomography/computed tomography (PET/CT) for gradually elevated alpha
      Fetoprotein level. Multiple masses in the abdominal cavity with moderate FDG
      uptake were revealed, suggesting malignant tumor with peritoneal metastasis. The
      patient underwent radical resection, and the postoperative pathological result
      was HAC originated from the appendix. To our knowledge, it is the first report of
      HAC of the appendix. Our study suggests that FDG PET/CT may help in detecting the
      primary tumor and the metastases of HAC. 

PMID- 24721023
TI  - In vitro comparison of two different mechanical circulatory support devices
      installed in series and in parallel.
AB  - This study investigates the novel approach of placing a ventricular assist pump
      in the descending aorta in series configuration with the heart and compares it
      with the two traditional approaches of left-ventricle-to-ascending-aorta (LV-AA)
      and left-ventricle-to-descending-aorta (LV-DA) placement in parallel with the
      heart. Experiments were conducted by using the in-house simulator of the
      cardiovascular blood-flow loop (SCVL). The results indicate that the use of the
      LV-AA in-parallel configuration leads to a significant improvement in the
      systemic and pulmonic flow as the level of continuous flow is increased; however,
      this approach is considered highly invasive. The use of the LV-DA in-parallel
      configuration leads to an improvement in the systemic and pulmonic flow at lower
      levels of continuous flow but at higher levels of pump support leads to
      retrograde flow. In both in-parallel configurations, increasing the level of pump
      continuous flow leads to a decrease in pulsatility to a certain extent. The
      results of placing the pump in the descending aorta in series configuration show
      that the pressure drop upstream of the pump facilitates cardiac output as a
      result of afterload reduction. In addition, the pressure rise downstream of the
      pump may assist with renal perfusion. However, at the same time, the pressure
      drop generated at the proximal part of the descending aorta induces a slight drop
      in carotid perfusion, which would be autoregulated by the brain in a native
      cardiovascular system. The pulse wave analysis shows that placing the pump in the
      descending aorta leads to improved pulsatility in comparison with the traditional
      in-parallel configurations. 

PMID- 24721024
TI  - A comparison of suprascapular nerve block and procedural sedation analgesia in
      shoulder dislocation reduction.
AB  - OBJECTIVES: Dislocation of the shoulder joint is one of the most common
      dislocations. The reduction procedure is a painful procedure. In this study, 2
      different treatment groups were compared for pain control during shoulder
      dislocation reduction. It was aimed to evaluate the differences between the
      groups in reduction, success, length of hospital stay, complications, side
      effects, patient-physician satisfaction, and ease of application. METHODS: The
      study was planned to be prospective and randomized. As procedural sedation
      analgesia (SA), titration of ketamine 1 to 2 mg/kg was administered intravenously
      to group 1. Suprascapular nerve block (SNB) was applied under ultrasound guidance
      (USG) to group 2. Conformity to normal distribution of variables was examined
      with the Kolmogorov-Smirnov test. The chi2 test and Fisher test were used to
      evaluate differences between the groups in categorical variables and the Mann
      Whitney U test, and a value of P<.05 was accepted as statistically significant.
      RESULTS: The study comprised a total of 41 patients; 20 in the group 1 and 21 in
      the group 2. No statistically significant difference was determined between the
      groups in terms of age (P=.916), sex (P=.972), reduction success (P=.540), and
      patient-physician satisfaction (P=.198). The time spent in the emergency
      department (ED) by patients in the SA group was signficantly longer compared with
      the SNB group. No side effects were observed in the SNB group. CONCLUSIONS:
      Suprascapular nerve block, which can be easily applied under USG in the ED, can
      be evaluated as a good alternative to SA in the reduction of shoulder
      dislocations.

PMID- 24721025
TI  - Rising rates of proton pump inhibitor prescribing in US emergency departments.
AB  - OBJECTIVE: There have been mounting safety concerns over increasing prescription
      rates for proton pump inhibitors (PPIs). Trends in PPI use have not been studied
      in emergency departments (EDs). We characterize trends in PPI use in US EDs.
      METHODS: We used data from the National Hospital Ambulatory Care Survey, from
      2001 to 2010, focusing on encounters with a reason for visit with a potential
      indication for a PPI, histamine receptor (H2) blocker, or antacid. Patient,
      provider, visit, and hospital-level factors associated with increases in PPI use
      were evaluated. RESULTS: Among included visits, ED PPI prescribing more than
      doubled from 3.0 (95% confidence interval [CI]: 2.4-3.8) to 7.2% (95% CI: 6.3
      8.3) from 2001 to 2010. Histamine receptor blocker use decreased from 6.8% (95%
      CI: 6.0-7.7) to 5.7% (95% CI: 4.9-6.7) and antacids from 7.2% (95% CI: 6.3-8.2)
      to 5.5% (95% CI: 4.8-6.3). Proton pump inhibitor prescribing was higher in males
      and whites yet increased across all demographics, including in adults aged 65
      years and older. Proton pump inhibitor prescribing increased significantly in all
      US regions and across all hospital and payer types. Pantoprazole was the agent
      with the largest increase in use. CONCLUSIONS: Over the past decade, there have
      been considerable increases in PPI prescribing in US EDs. This trend occurred
      despite rising safety concerns, even in populations at higher risk for adverse
      events such as older adults. More education may be needed to ensure that ED
      providers are familiar with indications for PPIs.

PMID- 24721026
TI  - Effect of tobacco smoke exposure during pregnancy and preschool age on growth
      from birth to adolescence: a cohort study.
AB  - BACKGROUND: There is strong evidence of an association between maternal smoking
      during pregnancy and restriction of intrauterine growth, but the effects of this
      exposure on postnatal linear growth are not well defined. Furthermore, few
      studies have investigated the role of tobacco smoke exposure also after pregnancy
      on linear growth until adolescence. In this study we investigated the effect of
      maternal smoking exposure during pregnancy and preschool age on linear growth
      from birth to adolescence. METHODS: We evaluated a cohort of children born
      between 1994 and 1999 in Cuiaba, Brazil, who attended primary health clinics for
      vaccination between the years 1999 and 2000 (at preschool age) and followed-up
      after approximately ten years. Individuals were located in public and private
      schools throughout the country using the national school census. Height/length
      was measured, and length at birth was collected at maternity departments. Stature
      in childhood and adolescence was assessed using the height-for-age index sex
      specific expressed as z-score from curves published by the World Health
      Organization. Linear mixed effects models were used to estimate the association
      between exposure to maternal smoking, during pregnancy and preschool age, and
      height of children assessed at birth, preschool and school age, adjusted for age
      of the children. RESULTS: We evaluated 2405 children in 1999-2000, length at
      birth was obtained from 2394 (99.5%), and 1716 at follow-up (71.4% of baseline),
      50.7% of the adolescents were male. The z-score of height-for-age was lower among
      adolescents exposed to maternal smoking both during pregnancy and childhood (p <
      0.01). Adjusting for age, sex, maternal height, maternal schooling, socioeconomic
      position at preschool age, and breastfeeding, children exposed to maternal
      smoking both during pregnancy and preschool age showed persistent lower height
      for-age since birth to adolescence (coefficient: -0.32, p < 0.001) compared to
      non-exposed. Paternal smoking at preschool age was not associated with growth
      after adjustment for confounders. CONCLUSION: Exposure to maternal smoking not
      only during pregnancy, but also at early childhood, showed long-term negative
      effect on height of children until adolescence.

PMID- 24721027
TI  - Antiinflammatory and neurological activity of pyrithione and related sulfur
      containing pyridine N-oxides from Persian shallot (Allium stipitatum).
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Persian shallot (Allium stipitatum) is a bulbous
      plant native to Turkey, Iran and Central Asia. It is frequently used in folk
      medicine for the treatment of a variety of disorders, including inflammation and
      stress. Antiinflammatory and neurological activities of pyrithione and four
      related sulfur-containing pyridine N-oxides which are prominent constituents of
      Allium stipitatum were tested. METHODS: The antiinflammatory activity was tested
      by the ability of the compounds to inhibit cyclooxygenase (COX-1 and COX-2),
      whereas the neurological activities were evaluated by assessing the compounds
      ability to inhibit monoamine oxidase-A (MAO-A) and acetylcholinesterase (AChE).
      The compounds' affinity for the serotonin transport protein (SERT) and the GABAA
      benzodiazepine receptor were also investigated. RESULTS: 2
      [(Methylthio)methyldithio]pyridine N-oxide showed very high antiinflammatory
      effects which are comparable with those of common pharmaceuticals (IC50 of 7.8
      and 15.4 uM for COX-1 and COX-2, respectively). On the other hand, neurological
      activities of the compounds were rather modest. Some compounds moderately
      inhibited AChE (IC50 of 104-1041 uM) and MAO-A (IC50 of 98-241 uM) and exhibited
      an affinity for the SERT and GABAA-benzodiazepine receptor. CONCLUSIONS: Our
      findings may help to rationalize the wide use of Persian shallot for the
      treatment of inflammatory disorders.

PMID- 24721038
TI  - Prenatal exposure to glucocorticoids affects body weight, serum leptin levels,
      and hypothalamic neuropeptide-Y expression in pre-pubertal female rat offspring.
AB  - Glucocorticoid secretion is a key endocrine response to stress. It has been
      reported that prenatal stress induces long-lasting alterations in body weight
      regulation systems, which persist after the stress has ceased. In this study, the
      long-term effects of prenatal glucocorticoid exposure on body weight changes and
      the expression of appetite-regulating factors were examined in female rats.
      Pregnant rats were given normal drinking water (control) or dexamethasone (1
      MUg/mL) dissolved in drinking water (DEX) from day 13 of pregnancy until
      delivery. Then, the body weight change, serum leptin levels, and hypothalamic NPY
      mRNA levels of their offspring were examined. The DEX dams gained significantly
      less body weight during pregnancy than the control dams. The DEX dams' offspring
      exhibited a significantly lower birth weight than the offspring of the control
      dams, and the same was true for body weight at postnatal days 20 and 28. The
      offspring of the DEX dams displayed significantly higher serum leptin levels and
      significantly lower hypothalamic NPY mRNA levels compared with the offspring of
      the control dams. Significant inverse correlations were detected between body
      weight and the serum leptin level, and between the serum leptin level and the
      hypothalamic NPY mRNA level. On the other hand, a significant positive
      correlation was detected between body weight and the hypothalamic NPY mRNA level.
      These results indicate that leptin production is increased in a long-lasting
      manner in offspring exposed to glucocorticoids during the prenatal period and
      that this results in attenuated body weight gain and hypothalamic NPY expression
      during the pre-pubertal period.

PMID- 24721041
TI  - Do family physicians need more payment for working better? Financial incentives
      in primary care.
AB  - INTRODUCTION: Financial incentives are widely used in health services to improve
      the quality of care or to reach some specific targets. Pay for performance
      systems were also introduced in the primary health care systems of many European
      countries. OBJECTIVE: Our study aims to describe and compare recent existing
      primary care indicators and related financing in European countries. METHODS:
      Literature search was performed and questionnaires were sent to primary care
      experts of different countries within the European General Practice Research
      Network. RESULTS: Ten countries have published primary care quality indicators
      (QI) associated with financial incentives. The number of QI varies from 1 to 134
      and can modify the finances of physicians with up to 25% of their total income.
      CONCLUSIONS: The implementations of these schemes should be critically evaluated
      with continuous monitoring at national or regional level; comparison is required
      between targets and their achievements, health gains and use of resources as
      well.

PMID- 24721039
TI  - Litter and sex effects on maternal behavior and DNA methylation of the Nr3c1 exon
      17 promoter gene in hippocampus and cerebellum.
AB  - Early life events can alter gene expression through DNA methylation. The
      methylation status of the exon 17 promoter of the glucocorticoid receptor (Nr3c1
      gene) in hippocampus associates with frequency of pup licking. Much of this work
      was conducted with male rats. Because dams more frequently lick male pups, this
      may contribute to sex differences in phenotypes through DNA methylation.
      Modifying litter gender composition (LGC), in which offspring of single-sex
      litters are compared to mixed-sex litters, alters maternal behavior. Previously,
      we demonstrated that LGC and sex affected pup licking times as well as anxiety
      and hippocampal DNA methylation of the Nr3c1 exon 17 promoter gene in
      adolescence. Now, we expand upon this work by examining effects in cerebellum and
      measuring mRNA levels. We also re-assessed DNA methylation in hippocampus using
      pyrosequencing and re-analyzed pup licking with the more commonly used frequency
      measure. Litters, culled to 8 pups on postnatal day 1 (PN1), were assigned to one
      of three conditions: all male (n = 10), all female (n = 12), or half of each sex
      (n = 20). Licking was rated on PN4, 7, and 10. On PN35, hippocampal and
      cerebellar samples were obtained. Single-sex males were licked the least and
      mixed-sex males, the most. Hippocampal Nr3c1 mRNA levels were lowest in mixed
      females with no LGC or Sex effects in DNA methylation. Cerebellar DNA methylation
      levels were lowest in mixed males with no effect on mRNA levels. Maternal pup
      licking associated with DNA methylation of the Nr3c1 exon 17 promoter gene in
      cerebellum and with hippocampal mRNA.

PMID- 24721040
TI  - Lifestyle medicine for depression.
AB  - The prevalence of depression appears to have increased over the past three
      decades. While this may be an artefact of diagnostic practices, it is likely that
      there are factors about modernity that are contributing to this rise. There is
      now compelling evidence that a range of lifestyle factors are involved in the
      pathogenesis of depression. Many of these factors can potentially be modified,
      yet they receive little consideration in the contemporary treatment of
      depression, where medication and psychological intervention remain the first line
      treatments. "Lifestyle Medicine" provides a nexus between public health promotion
      and clinical treatments, involving the application of environmental, behavioural,
      and psychological principles to enhance physical and mental wellbeing. This may
      also provide opportunities for general health promotion and potential prevention
      of depression. In this paper we provide a narrative discussion of the major
      components of Lifestyle Medicine, consisting of the evidence-based adoption of
      physical activity or exercise, dietary modification, adequate relaxation/sleep
      and social interaction, use of mindfulness-based meditation techniques, and the
      reduction of recreational substances such as nicotine, drugs, and alcohol. We
      also discuss other potential lifestyle factors that have a more nascent evidence
      base, such as environmental issues (e.g. urbanisation, and exposure to air,
      water, noise, and chemical pollution), and the increasing human interface with
      technology. Clinical considerations are also outlined. While data supports that
      some of these individual elements are modifiers of overall mental health, and in
      many cases depression, rigorous research needs to address the long-term
      application of Lifestyle Medicine for depression prevention and management.
      Critically, studies exploring lifestyle modification involving multiple lifestyle
      elements are needed. While the judicious use of medication and psychological
      techniques are still advocated, due to the complexity of human illness/wellbeing,
      the emerging evidence encourages a more integrative approach for depression, and
      an acknowledgment that lifestyle modification should be a routine part of
      treatment and preventative efforts. 

PMID- 24721042
TI  - Interleukin-6 and tumour necrosis factor-alpha differentially regulate lincRNA
      transcripts in cells of the innate immune system in vivo in human subjects with
      rheumatoid arthritis.
AB  - lincRNAs recently have been discovered as evolutionary conserved transcripts of
      non-coding DNA sequences and have been implicated in the regulation of cellular
      differentiation. In humans, molecular studies have suggested a functional role
      for lincRNAs in cancer development. The aim of the present study was to examine
      whether these novel molecules are specifically regulated by different cytokines
      in cells of the innate immune system in humans in vivo and whether lincRNAs
      thereby might be involved in the pathophysiology of rheumatoid arthritis (RA).
      Therefore, CD14(+) monocytes were isolated from RA patients before and after anti
      IL-6R (tocilizumab) or anti-TNF-alpha (adalimumab) therapy and lincRNA
      transcription was analysed by a microarray based experiment. As expected, we
      found lincRNAs to be present in CD14(+) monocytes of RA patients. However, of the
      total number of 7.419 lincRNAs examined in this study only a very small number
      was significantly regulated by either IL-6 or TNF-alpha (85 lincRNAs,
      corresponding to 1.1%). The numbers of lincRNAs regulated was higher due to TNF
      alpha compared to IL-6. Interestingly, none of the identified lincRNAs was
      influenced by both, IL-6 and TNF-alpha, suggesting the regulation of lincRNA
      transcription to be highly specific for distinct cytokines. Taken together, our
      results suggest (1) that lincRNAs are novel intracellular molecular effectors of
      specific cytokines in cells of the innate immune system in humans in vivo and (2)
      that lincRNAs might be involved in the molecular pathophysiology of RA. 

PMID- 24721043
TI  - Characteristics of extracellular polymeric substances of phototrophic biofilms at
      different aquatic habitats.
AB  - Three different phototrophic biofilms obtained from a natural lake (Sample 1),
      drinking water plant (Sample 2) and wastewater treatment plant (Sample 3) were
      investigated. Diatoms and green algae were the dominant algae of three biofilms,
      and the biomass was highest in biofilm of Sample 2. The three phototrophic
      biofilms also had variable extracellular polymeric substances (EPS)
      concentrations and compositions. Total EPS concentration of 14.80 mg/g DW was
      highest in biofilm of Sample 2, followed by biofilms of Samples 3 and 1 (13.11
      and 12.29 mg/g DW). Tightly bound EPS (TB-EPS) were the main fraction, and
      polysaccharides and protein were the main components of total EPS in all three
      biofilms. However, the compositions of loosely bound EPS (LB-EPS) and TB-EPS were
      different in three biofilms. Fourier-transform infrared and fluorescence spectra
      indicated different structure and compositions of LB-EPS and TB-EPS. These
      results demonstrated the characteristics of EPS produced by phototrophic biofilms
      varied and had compact relation to their growth environmental conditions.

PMID- 24721044
TI  - Improvement production of bacterial cellulose by semi-continuous process in
      molasses medium.
AB  - Bacterial cellulose (BC) has unique properties such as structural, functional,
      physical and chemical. The mass production of BC for industrial application has
      recently become attractive to produce more economical and high productive
      cellulose. In this study, to improve the productivity of bacterial cellulose
      (BC), BC production by Gluconacetobacter xylinus FC01 was investigated in
      molasses medium with static semi-continuous operation mode. Cell dry weight,
      polysaccharide, sugar and cellulose concentrations were monitored and cellulose
      was characterized by Fourier transform infrared spectroscopy (FT-IR) and scanning
      electron microscopy (SEM). The highest cellulose yield (1.637 g/L) was obtained
      in SCP50-7d, which molasses of 1/2 ratio for 7 days by static semi-continuous
      operation mode. The results show that BC can be highly produced by G. xylinus in
      molasses with static semi-continuous process than batch process. We claimed that
      low-cost medium with semi-continuous operation mode in static culture is a good
      candidate for industrial scale BC productions.

PMID- 24721045
TI  - Compare study cellulose/Ag hybrids using fructose and glucose as reducing
      reagents by hydrothermal method.
AB  - The primary objective of this work was to evaluate the effect of reducing
      reagents on the hybrids from cellulose and Ag, which have been successfully
      synthesized by using fructose and glucose as reducing reagents via a hydrothermal
      method, respectively. The hybrids were characterized by X-ray powder diffraction
      (XRD), scanning electron microscopy (SEM), thermogravimetric analysis (TGA), and
      differential thermal analysis (DTA). The influences of the various reaction
      parameters including the heating time, heating temperature, and types of reducing
      reagents on the hybrids were investigated. Silver particles can be better
      dispersed in the cellulose matrix by adjusting reaction parameters. Experimental
      results demonstrated that the types of reducing reagents played an important role
      in the shape and dispersion of silver particles in hybrids. 

PMID- 24721046
TI  - Preparation and antioxidant activity of the oligosaccharides derived from
      Laminaria japonica.
AB  - Hydrogen peroxide (H2O2) can degrade polysaccharides and has bleaching effect. In
      this study, the oligosaccharides derived from Laminaria japonica were prepared by
      hydrolysis with H2O2 and their antioxidant activity was investigated. The optimal
      hydrolysis conditions were determined as follows: reaction time 24h, reaction
      temperature 75 degrees C, and H2O2 concentration 4%. Under the optimum
      conditions, the maximum yield of the oligosaccharides reached 17.65%, which was
      higher than that of aqueous extraction, and at the same time, the maximal
      decoloration rate reached 79.85%. The oligosaccharides sample contained 94.82%
      sugar, of which the average degree was approximately 8, and showed light green.
      The oligosaccharides derived from L. japonica showed high hydroxyl radical
      scavenging activity (91.31%) at the concentration of 100 MUg/mL.

PMID- 24721047
TI  - Characterisation of hyaluronic acid and chondroitin/dermatan sulfate from the
      lumpsucker fish, C. lumpus.
AB  - The lumpsucker, Cyclopterus lumpus, a cottoid teleost fish found in the cold
      waters of the North Atlantic, and North Pacific, was identified as a possible
      source of GAGs. The GAGs present in the C. lumpus dorsal hump and body wall
      tissue were isolated and purified. Two fractions were analysed by NMR and their
      GAG structures determined as hyaluronic acid and CS/DS chains. The latter
      fraction contained GlcA (65% of the total uronic acids) and IdoA (the remaining
      35%). All uronic acid residues were unsulfated, whilst 86% of the GalNAc was 4
      sulfated and 14% was 6-sulfated. The presence of GlcA-GalNAc4S, IdoA-GalNAc4S and
      GlcA-GalNAc6S disaccharide fragments was confirmed. The isolated GAGs obtained
      from each tissue were biochemically characterised. The lumpsucker offers a high
      yield source of GAGs, which compares favourably with other sources such as shark
      cartilage.

PMID- 24721048
TI  - Nanogel and superparamagnetic nanocomposite based on sodium alginate for sorption
      of heavy metal ions.
AB  - Novel sodium alginate supported tetrasodium thiacalix[4]arene tetrasulfonate
      (TSTC[4]AS-s-SA) nanogel was prepared using sodium alginate nanoparticles. Then,
      superparamagnetic nanocomposite of sodium alginate (Fe3O4@TSTC[4]AS-s-SA) was
      fabricated from coprecipitation of sodium alginate supported tetrasodium
      thiacalix[4]arene tetrasulfonate and in situ generated Fe3O4 nanoparticles.
      Structural, morphological, surface, thermal and magnetic properties of the
      nanoadsorbents were studied by Fourier transform infrared (FT-IR), X-ray
      diffraction (XRD), scanning electron microscopy (SEM), transmission electron
      microscopy (TEM), atomic force microscopy (AFM), differential scanning
      calorimetry (DSC), thermal gravimetric analysis (TGA), and vibrating sample
      magnetometer (VSM), respectively. Adsorptions of Cu(II), Cd(II), Pb(II), Co(II),
      Ni(II) and Cr(III) ions onto nanoadsorbents were studied in aqueous condition at
      pH=7. The results indicated that incorporation of thiacalix[4]arene
      tetrasulfonate and Fe3O4 into sodium alginate nanoparticles increased the
      adsorption capacity of sodium alginate bioadsorbents, and led to the magnetic
      property. The TSTC[4]AS-s-SA nanogels consist of rod-like structure with an
      average diameter of 50 nm.

PMID- 24721049
TI  - Preparation, antiangiogenic and antitumoral activities of the chemically sulfated
      glucan from Phellinus ribis.
AB  - Two sulfated derivatives (PRP-S1 and PRP-S2) of a beta-glucan from Phellinus
      ribis with different degrees of substitution were obtained by chlorosulfonic acid
      method. The derivatives could block formation of new vessels in zebrafish and
      inhibit the proliferation of human umbilical vein endothelial cells (HUVECs). The
      two sulfated derivatives had remarkably high antitumor activities in vivo (in
      BALB/c mice inoculated with H22 hepatocellular carcinoma) as well as in vitro
      (against human ovary cancer SKOV-3 cells), without producing any overt signs of
      general toxicity. The results of immunohistochemistry assay indicated that the
      derivatives significantly reduced the average number of microvessel density (MVD)
      and inhibited the expression of vascular endothelial growth factor (VEGF) in
      tumor. Thus, these derivatives exhibit pronounced antiangiogenic and antitumoral
      properties. Except for cytotoxic effects on tumor cells, it is reasonable to
      expect that the antitumoral effects of PRP-S1 and PRP-S2 are mediated via their
      antiangiogenic properties.

PMID- 24721050
TI  - Synthesis and characterization of selective thiourea modified Hg(II) ion
      imprinted cellulosic cotton fibers.
AB  - In the present study, Hg(2+) ion-imprinted chelating fibers based on thiourea
      modified natural cellulosic cotton fibers (Hg-C-TU) were synthesized and
      characterized using some instrumental techniques such as elemental analysis,
      scanning electron microscopy (SEM), FTIR, wide angle X-ray and XPS spectroscopy.
      The modified Hg-C-TU fibers were employed for selective removal of Hg(2+) from
      aqueous solution. Effect of some essential parameters such as pH, temperature,
      adsorption times and adsorbate concentration were examined to evaluate the
      optimum adsorption condition. The adsorption kinetics followed the second-order
      kinetic model indicating that the chemical adsorption is the rate limiting step.
      Also, the adsorption isotherm experiments showed the best fit with Langmuir model
      with maximum adsorption capacities 110.3 and 61.8 mg/g for both Hg-C-TU and NI-C
      TU, respectively.

PMID- 24721051
TI  - Thermal degradation behavior and kinetic analysis of spruce glucomannan and its
      methylated derivatives.
AB  - The thermal degradation behavior and kinetics of spruce glucomannan (SGM) and its
      methylated derivatives were investigated using thermogravimetric analysis to
      characterize its temperature-dependent changes for use in specific applications.
      The results were compared with those obtained for commercial konjac glucomannan
      (KGM). The SGM and the KGM exhibited two overlapping peaks from 200 to 375
      degrees C, which correspond to the intensive devolatilization of more than 59% of
      the total weight. Differences in the pyrolysis-product distributions and thermal
      stabilities appeared as a result of the different chemical compositions and
      molecular weights of the two GMs. The Friedman and Flynn-Wall-Ozawa
      isoconversional methods and the Coats-Redfern were adopted to determine the
      kinetic triplet of the intensive devolatilization region. Both GMs can be modeled
      using a complex mechanism that involves both a Dn-type and an Fn-type reaction.
      The comparative study of partially methylated GM indicated higher homogeneity and
      thermal resistance for the material with the higher degree of substitution. 

PMID- 24721052
TI  - Purification and characterization of a novel marine Arthrobacter oxydans KQ11
      dextranase.
AB  - Dextranases can hydrolyze dextran deposits and have been used in the sugar
      industry. Microbial strains which produce dextranases for industrial use are
      chiefly molds, which present safety issues, and dextranase production from them
      is impractically long. Thus, marine bacteria to produce dextranases may overcome
      these problems. Crude dextranase was purified by a combination of ammonium
      sulfate fractionation and ion-exchange chromatography, and then the enzyme was
      characterized. The enzyme was 66.2 kDa with an optimal temperature of 50 degrees
      C and a pH of 7. The enzyme had greater than 60% activity at 60 degrees C for 1h.
      Moreover, 10mM Co(2+) enhanced dextranase activity (196%), whereas Ni(2+) and
      Fe(3+) negatively affected activity. 0.02% xylitol and 1% alcohol enhanced
      activity (132.25% and 110.37%, respectively) whereas 0.05% SDS inhibited activity
      (14.07%). The thickness of S. mutans and mixed-species oral biofilm decreased
      from 54,340 nm to 36,670 nm and from 64,260 nm to 43,320 nm, respectively.

PMID- 24721053
TI  - Characterization of a new natural fiber from Arundo donax L. as potential
      reinforcement of polymer composites.
AB  - The aim of this paper is to study the possibility of using of Arundo donax L.
      fibers as reinforcement in polymer composites. The fibers are extracted from the
      outer part of the stem of the plant, which widely grows in Mediterranean area and
      is diffused all around the world. To use these lignocellulosic fibers as
      reinforcement in polymer composites, it is necessary to investigate their
      microstructure, chemical composition and mechanical properties. Therefore, the
      morphology of A. donax L. fibers was investigated through electron microscopy,
      the thermal behavior through thermogravimetric analysis and the real density
      through a helium pycnometer. The chemical composition of the natural fibers in
      terms of cellulose, hemicellulose, lignin, and ash contents was determinated by
      using standard test methods. The mechanical characterization was carried out
      through single fiber tensile tests and a reliability analysis of the experimental
      data was performed. Furthermore, a mathematical model was applied to investigate
      the relation between the transverse dimension of the fibers and the mechanical
      properties.

PMID- 24721054
TI  - Characterization and properties of carboxymethyl cellulose hydrogels crosslinked
      by polyethylene glycol.
AB  - Novel hydrogels were prepared from carboxymethyl cellulose (CMC) sodium salt by
      crosslinking with polyethylene glycol diglycidyl ether (PEGDE). The detailed
      structures of the hydrogels were determined via FTIR and solid-state NMR
      spectroscopic analyses. Increasing the feed ratio of PEGDE to CMC in the reaction
      mixture led to an increase in the crosslinking degree, which enhanced the
      physical strength of the hydrogels. The hydrogels exhibited enzyme degradability,
      and after 3 days of incubation with cellulase, 62-28 wt% of the CMC in the
      hydrogel was degraded under the conditions employed in this study. In addition,
      the hydrogels exhibited protein adsorption and release abilities, and the amounts
      of proteins adsorbed on the hydrogels and the release profile of the proteins
      depended on the protein sizes and crosslinking degree of the hydrogels. These
      unique properties might enable the use of CMC-based hydrogels as drug delivery
      system carriers for protein-based drugs if the biological safety of the hydrogel
      can be verified.

PMID- 24721055
TI  - Efforts on membrane properties and enzymes by adding divalent cations and sodium
      carboxymethyl cellulose.
AB  - In this paper, the addition of sodium carboxymethyl cellulose (NACMC) and cobalt
      ions to alginate gel significantly improved the inner and outer surface
      properties of membranes and the activity of the enzymes. The results showed the
      optimization was sodium alginate (SA) and NACMC at ratio 1:1, and the
      concentration of CoCl2 at 0.05 mol/L. The combined SA-NACMC gel bead apparently
      had a more porous and higher mechanical strength than that of the SA gel bead by
      scanning electron microscopy (SEM). The microcapsule surface roughness was
      measured by atomic force microscopy (AFM), the roughness was 155 +/- 15.82 mm.
      Otherwise, the Brunauer-Emmett-Teller (BET) analysis showed that with the
      addition of NACMC the surface area and most of pore size of the microcapsules was
      76.471 m(2)/g, and distributed in 3-25 nm, respectively. In 28 d, immobilized
      enzyme had a higher degradation rate, and the atrazine residue of the immobilized
      enzyme with 5% content was 21.79%.

PMID- 24721056
TI  - Intermolecular complexation of low-molecular-weight succinoglycans directs
      solubility enhancement of pindolol.
AB  - The low-molecular-weight succinoglycans isolated from Sinorhizobium meliloti are
      repeating octasaccharide units consisting of monomers, dimers, and trimers.
      Pindolol is a beta-blocker used to treat cardiovascular disorders. We
      investigated the formation of complexes between pindolol and low-molecular-weight
      succinoglycan monomers (SGs). Even though SGs have a linear structure, the
      solubility of pindolol in the presence of SGs was increased up to 7-fold compared
      with methyl-beta-cyclodextrin reported as the best solubilizer of pindolol.
      Complexation of SGs with pindolol was confirmed by nuclear magnetic resonance,
      Fourier-transform infrared spectroscopy, differential scanning calorimetry, and
      scanning electron microscopy. Formation constants of complexes were determined
      from phase solubility diagrams. Conformation of complex was suggested based on a
      molecular docking study. The present study indicated that formation of
      pindolol/SGs complexes not only resulted in increased pindolol solubility but
      also could be useful for improving its clinical application as it did not affect
      cell viability.

PMID- 24721057
TI  - Controlled release of tinidazole and theophylline from chitosan based composite
      hydrogels.
AB  - Several composite hydrogels were synthesized by free radical crosslink
      copolymerization of acrylic acid (AA) and N' methylene bis-acrylamide (MBA) in
      the presence of chitosan (CS). During polymerization CS was incorporated in situ
      in the crosslinked polyacrylic acid gel to produce composite hydrogels. The
      structure and properties of the hydrogels were characterized by FTIR, (13)C NMR,
      DTA-TGA, XRD, swelling and diffusion characteristic and also network parameters.
      The loading and the in vitro release behaviours of theophylline and tinidazole
      model drugs were studied with these hydrogels. The wt% of CS and MBA and pH of
      the medium was found to strongly influence the drug release behaviour of the
      gels. Accordingly, the release rate of these two drugs was much faster at pH of
      7.6 than at pH 1.5. 

PMID- 24721058
TI  - Phosphorylation of Kraft fibers with phosphate esters.
AB  - Phosphate esters, derived from two different long-chain aliphatic alcohols, were
      used as phosphorylating reagents for Kraft pulp fibers. High phosphorus contents
      and almost non-degraded fibers were obtained by following this pathway. The
      phosphorylation efficiency was influenced by the alkyl chain length of PEs since
      the phosphorus content in modified fibers was higher for the shorter chain
      reagent. Due to the heterogeneous reaction environment, the amount of grafted
      phosphorus was found to be almost three times higher at the surface than in the
      bulk of the fibers. Analyses also indicated that the phosphorus was bonded to
      fibers as a phosphate-like structure. Furthermore, the situation seemed to be
      different for the fiber surface where significant amounts of phosphorus were
      present in more complex structures like pyrophosphate or even oligo-phosphate. 

PMID- 24721059
TI  - Origin of chiral interactions in cellulose supra-molecular microfibrils.
AB  - The formation of a chiral-nematic phase from cellulose nanowhiskers has been
      frequently reported in the literature. The most popular theory used to explain
      the chiral interactions is that of twisted morphology of cellulose nanowhiskers.
      Two possible origins of twist have been suggested: the intrinsic chirality of
      cellulose chains and result of interaction of chiral surfaces. High resolution
      SEM and AFM have been used to locate twists in cellulose microfibrils and
      nanowhiskers. The origin of the twisted morphology in cellulose microfibrils has
      been studied with reference to the protein aggregation theory. 

PMID- 24721060
TI  - Physical, structural, mechanical and thermal characterization of bacterial
      cellulose by G. hansenii NCIM 2529.
AB  - The present study aims to investigate the physico mechanical, structural and
      thermal properties of the bacterial cellulose (BC) produced under shaking
      condition. Formation of characteristic cellulose sphere has been characterized by
      light and scanning electron microscopy. The purity of bacterial cellulose was
      confirmed by thin layer chromatography of hydrolyzed product and elemental
      analysis by Energy Dispersive Spectroscopy and Fourier transform infrared
      spectroscopy. High crystallinity bacterial cellulose (81%) composed by high
      Ialpha confirmed by X-ray diffraction and solid state C13 nuclear magnetic
      resonance spectroscopy. The Z-average particle size was 1.44 MUm with high
      porosity of 181.81%. The water holding and absorption capacity was determined.
      Tensile strength reveals a Young's modulus of 15.71 +/- 0.15 MPa and tensile
      strength of up to 14.94 MPa. The thermal behavior evaluated by thermogravimetry
      and differential scanning calorimetry shows the thermal stability of bacterial
      cellulose. The results demonstrated unique characteristics of bacterial cellulose
      produced at shaking condition.

PMID- 24721061
TI  - One-sided surface modification of cellulose fabric by printing a modified TEMPO
      mediated oxidant.
AB  - One-sided surface oxidation of lyocell type cellulose fabric can be achieved by
      use of a modified TEMPO-mediated oxidation system. A borate-based buffer was used
      to maintain stable pH conditions and screen printing was applied to achieve
      oxidation on the fabric surface only. To formulate an applicable procedure, the
      TEMPO/NaBr/NaOCl system was split into two treatment steps: firstly, the fabric
      was impregnated with a buffered TEMPO/NaBr solution and dried, then a thickened
      NaOCl paste was printed on the fabric. FTIR-ATR spectra and methylene blue
      sorption experiments demonstrated successful modification on the printed side of
      the fabric. Substantial increases in carboxylic group content and water retention
      value were observed. The higher concentration of carboxylic groups on the fabric
      surface also led to a localised increase in binding capacity for Ca(2+)-ions.
      This new concept permits controlled oxidation of cellulose surfaces by printing
      techniques.

PMID- 24721062
TI  - A world of low molecular weight heparins (LMWHs) enoxaparin as a promising moiety
      -a review.
AB  - Anti-coagulants are one of the most important categories in healthcare
      therapeutics. For healthcare professionals dealing in cases of in-vivo blood
      clotting problems. Heparin and low molecular weight heparins (LMWHs) would be the
      first choice of drugs. This review represents an overview of the LMWHs, their
      importance over heparin and enlightens the advancements. In addition to these,
      different methods used for preparation and purification are discuss in terms of
      production and synthesis. Worldwide availability in pre-filled syringe, market,
      manufacturers and suppliers drug interactions, adverse drug reactions, in-vitro
      study, freezing/thawing process and structural differences of LMWHs are also
      focused upon in this review.

PMID- 24721063
TI  - Facile and rapid thermo-regulated biomineralization of gold by pullulan and study
      of its thermodynamic parameters.
AB  - A novel method for the production of gold nanoparticles (AuNPs) using pullulan as
      reducing and stabilizing agent has been developed. Quasi-spherical shaped AuNPs
      in the range of 50-100 nm were produced at three different temperature regimes 80
      degrees C, 90 degrees C and 100 degrees C as characterized using UV-vis
      spectrophotometer, TEM and DLS. Study of reaction kinetics and thermodynamic
      parameters indicated that the reaction between pullulan and chloroauric acid for
      AuNPs formation followed first order reaction kinetics and higher temperature was
      favorable for the synthesis of smaller sized AuNPs. FT-IR data analyses, provided
      an insight towards the mechanism of gold nanoparticle formation which suggested
      that, the free CH2OH groups of pullulan molecule were oxidized to carboxylate
      ions resulted in formation of AuNPs whereas the basic skeletal structure of
      pullulan remained unaltered. This study may open up new avenues for synthesis of
      tailor made biogenic AuNPs with possible application in biomedical field.

PMID- 24721064
TI  - Synthesis of kenaf cellulose carbamate using microwave irradiation for
      preparation of cellulose membrane.
AB  - Cellulose carbamate (CCs) was produced from kenaf core pulp (KCP) using microwave
      reactor-assisted method. The effects of urea concentration and reaction time on
      the formation of nitrogen content in CCs were investigated. The CCs' solubility
      in LiOH/urea system was determined and its membranes were characterized. As the
      urea content and reaction time increased, the nitrogen content form in CCs
      increased which enhanced the CCs' solubility. The formation of CCs was confirmed
      by Fourier transform infrared spectroscopy (FT-IR) and nitrogen content analysis.
      The CCs' morphology was examined using Scanning electron microscopy (SEM). The
      cellulose II and crystallinity index of the membranes were confirmed by X-ray
      diffraction (XRD). The pore size of the membrane displayed upward trend with
      respect to the urea content observed under Field emission scanning electron
      microscope (FESEM). This investigation provides a simple and efficient procedure
      of CCs determination which is useful in producing environmental friendly
      regenerated CCs.

PMID- 24721065
TI  - Characterisation of cationic potato starch by asymmetrical flow field-flow
      fractionation. Influence of ionic strength and degree of substitution.
AB  - The properties of a paper sheet depend on the absorption together with the
      physico-chemical properties of additives used in the paper processing. The effect
      of ionic strength and degree of substitution of cationic potato starch on the
      elution pattern of asymmetrical flow field-flow fractionation was analysed. The
      effect of starch derivatisation, in either dry or wet phase, was also
      investigated. Average molar mass showed no difference between the starches
      obtained from the two derivatisation processes. Apparent densities showed that
      dry cationic starch had higher density than wet cationic starch for a
      hydrodynamic radius between 50 and 100 nm. Elution times of native and three
      cationic starches increased when the ionic strength increased from 50 to 100mM.
      No differences in the molar mass among cationic starches with different degree of
      substitution suggested no degradation due to a derivatisation process. Large
      sample loads can be used at 100mM without overloading.

PMID- 24721066
TI  - Dissolution of mechanically milled chitin in high temperature water.
AB  - Chitin is high in crystallinity in its natural form and does not dissolve into
      high temperature water (HTW), which often leads to decomposition reactions such
      as hydrolysis, deacetylation and dehydration when hydrothermally processed. In
      this work, we investigated the reactions of mechanically milled chitin in HTW.
      Mechanical milling pretreatment combined with HTW treatment improved the
      liquefaction of chitin giving a maximum water soluble fraction of 80%, where the
      untreated chitin was 55%. The reaction mechanism of the milled and raw chitin in
      HTW was shown to be different. For milled chitin, the dissolution of chitin
      occurred during the heating period to supercritical water conditions (400 degrees
      C) at short reaction times (1 min). Extended reaction time (10 min) led to
      decomposition products and aromatic char formation. For raw chitin, the
      dissolution of chitin in HTW did not occur, due to its high crystallinity, so
      that liquefaction proceeded via decomposition reactions.

PMID- 24721067
TI  - Ultrasound-assisted extraction of pectins from grape pomace using citric acid: a
      response surface methodology approach.
AB  - An ultrasound-assisted procedure for the extraction of pectins from grape pomace
      with citric acid as the extracting agent was established. A Box-Behnken design
      (BBD) was employed to optimize the extraction temperature (X1: 35-75 degrees C),
      extraction time (X2: 20-60 min) and pH (X3: 1.0-2.0) to obtain a high yield of
      pectins with high average molecular weight (MW) and degree of esterification (DE)
      from grape pomace. Analysis of variance showed that the contribution of a
      quadratic model was significant for the pectin extraction yield and for pectin MW
      whereas the DE of pectins was more influenced by a linear model. An optimization
      study using response surface methodology was performed and 3D response surfaces
      were plotted from the mathematical model. According to the RSM model, the highest
      pectin yield (~32.3%) can be achieved when the UAE process is carried out at 75
      degrees C for 60 min using a citric acid solution of pH 2.0. These pectic
      polysaccharides, composed mainly by galacturonic acid units (<97% of total
      sugars), have an average MW of 163.9 kDa and a DE of 55.2%. Close agreement
      between experimental and predicted values was found. These results suggest that
      ultrasound-assisted extraction could be a good option for the extraction of
      functional pectins with citric acid from grape pomace at industrial level.

PMID- 24721068
TI  - Properties and characterization of bionanocomposite films prepared with various
      biopolymers and ZnO nanoparticles.
AB  - This study was aimed to develop biopolymer based antimicrobial films for active
      food packaging and to reduce environmental pollution caused by accumulation of
      synthetic packaging. The ZnO NPs were incorporated as antimicrobials into
      different biopolymers such as agar, carrageenan and CMC. Solvent casting method
      was performed to prepare active nanocomposite films. Methods such as FE-SEM, FT
      IR and XRD were used to characterize resulting films. Physical, mechanical,
      thermal and antimicrobial properties were also examined. Remarkable surface
      morphological differences were observed between control and nanocomposite films.
      The crystallinity of ZnO was confirmed by XRD analysis. The addition of ZnO NPs
      increased color, UV barrier, moisture content, hydrophobicity, elongation and
      thermal stability of the films, while decreased WVP, tensile strength and elastic
      modulus. ZnO NPs impregnated films inhibited growth of L. monocytogenes and E.
      coli. So these newly prepared nanocomposite films can be used as active packaging
      film to extend shelf-life of food. 

PMID- 24721069
TI  - Characterization of Citrus pectin edible films containing transglutaminase
      modified phaseolin.
AB  - The growing social and economic consequences of pollution derived from plastics
      are focusing attention on the need to produce novel bioprocesses for enhancing
      food shelf-life. As a consequence, in recent years the use of edible films for
      food packaging is generating a huge scientific interest. In this work we report
      the production of an edible hydrocolloid film made by using Citrus pectin and the
      protein phaseolin crosslinked by microbial transglutaminase, an enzyme able to
      covalently modify proteins by formation of isopeptide bonds between glutamine and
      lysine residues. The films were characterized and their morphology was evaluated
      by both atomic force microscopy and scanning electron microscopy. Mechanical
      properties and barrier properties to CO2, O2 and water vapor have demonstrated
      that these films possess technological features comparable to those possessed by
      commercial plastics. It is worth noting that these characteristics are maintained
      even following storage of the films at 4 degrees C or -20 degrees C, suggesting
      that our bioplastics can be tailored to protect food at low temperature.
      Moreover, gastric and duodenal digestion studies conducted under the same
      conditions found in the human digestion system have demonstrated that
      transglutaminase-containing films are regularly digested encouraging an
      application of the proposed materials as food coatings.

PMID- 24721070
TI  - Reaction of phosphorylase-a with alpha-D-glucose 1-phosphate and maltodextrin
      acceptors to give products with degree of polymerization 6-89.
AB  - A series of linear glucan saccharides (GS) with defined quantity and degree of
      polymerization (DP) were synthesized from alpha-d-glucose 1-phosphate (alpha-d
      Glc 1-P) by phosphorylase-a. The GS product fractions with average DP 11, 22, 38,
      52, 60, 70, and 79 were measured by HPSEC-ELSD system. Then the same seven
      fractions were resolved into individual peaks with DP: 6-14, 10-32, 27-55, 37-67,
      44-75, 49-83 and 53-89 by HPAEC-PAD system. Results showed that measurement of
      alpha-d-Glc 1-P amount consuming during GS synthesis by both systems enable
      calculation of reaction yield. The reaction yield for the 24h biosynthesis of the
      GS product was 25.3% (measured by HPSEC-ELSD) or 29.1% (measured by HPAEC-PAD).
      The HPSEC-ELSD and HPAEC-PAD systems were also successfully used for
      phosphorylase-a activity measurement in order to perform its kinetic
      characterization. This study established feasible systems for preparation of
      various sizes of the GS with defined DP and quantity as well as characterization
      of phosphorylase-a kinetics.

PMID- 24721071
TI  - Purification, preliminary characterization and in vitro immunomodulatory activity
      of tiger lily polysaccharide.
AB  - A water-soluble polysaccharide (LLPS) from tiger lily was extracted by ultrasonic
      wave-assisted extraction. The LLPS, which was isolated by alcohol precipitation,
      was further purified by DEAE Sepharose Fast Flow and Sephadex G-100
      chromatography, which resulted in LLPS fractions in LLPS-1, LLPS-2 and LLPS-3,
      with molecular weights of 350.5, 403.3 and 146.2kDa, respectively. LLPS-1 and
      LLPS-2 primarily consisted of glucose and mannose in a molar ratio of nearly 1:2
      and 1:1, respectively. In contrast, LLPS-3 was primarily composed of arabinose,
      galactose, glucose and mannose in a molar ratio of nearly 2:2:2:1. LLPS fractions
      could stimulate the proliferation of macrophages. The in vitro immunomodulatory
      activity of the fractions was evaluated. The results showed that treatment with
      25-400 MUg/mL of LLPS fractions could increase phagocytic activity and nitric
      oxide production of macrophages in a dose-dependent manner.

PMID- 24721072
TI  - Expression of HpaI in Pichia pastoris and optimization of conditions for the
      heparinase I production.
AB  - Heparinase I has important applications in the fields of biomedicine and
      pharmaceuticals. The heparinase I gene (HpaI) from Flavobacterium heparinum was
      cloned and overexpressed in Pichia pastoris GS115, and the conditions for the
      heparinase I production were optimized by RSM. PCR analysis indicated that HpaI
      was integrated into the P. pastoris GS115 genome. The concentrations of key
      factors that affected the heparinase I activity were optimized, and were as
      follows: oleic acid, 0.07%, liquid volume in flask, 34.3 ml/L, and methanol,
      0.96%. Under the optimal conditions, the activity of heparinase I was up to 323
      U/L in shake flask. A maximal heparinase I activity of 398.5 U/L from the
      transformant 2 was achieved in a 5L fermentor. This study demonstrates the
      overproduction of heparinase I by recombinant P. pastoris.

PMID- 24721073
TI  - Determining the solution conformational entropy of oligosaccharides by SEC with
      on-line viscometry detection.
AB  - Introduced here is a method for determining the solution conformational entropy
      of oligosaccharides (-DeltaS) that relies on the on-line coupling of size
      exclusion chromatography (SEC), an entropically-controlled separation technique,
      and differential viscometry (VISC). Results from this SEC/VISC method were
      compared, for the same injections of the same sample dissolutions and under
      identical solvent/temperature conditions, to results from a benchmark
      SEC/differential refractometry (SEC/DRI) method which has been applied
      successfully over the last decade to determining -DeltaS of a variety of mono-,
      di-, and oligosaccharides. The accuracy (as compared to SEC/DRI) and precision of
      SEC/VISC were found to be excellent, as was the sensitivity of the viscometer in
      the oligomeric region. The experiments presented here contrast three sets of (1
      >4)-beta-d-oligosaccharides, namely manno-, cello-, and N
      acetylchitooligosaccharides of degree of polymerization (DP) 2 through 6. For
      each series, the dependence of -DeltaS on DP was found to be monotonic while,
      between series, differences at each DP could be ascribed to either the additional
      degrees of freedom imparted by large, multi-atomic substituent groups, or to the
      presence or absence of additional intramolecular hydrogen bonds, depending on the
      axial versus equatorial arrangement of particular hydroxyl groups. An hypothesis
      is advanced to explain the unexpectedly high sensitivity of viscometric detection
      for low-molar-mass analytes. The method presented can be extended to the analysis
      of oligosaccharides other than those studied here.

PMID- 24721074
TI  - Optimization of polysaccharides from Zagros oak leaf using RSM: antioxidant and
      antimicrobial activities.
AB  - Ultrasonic assisted-extraction technique was applied to extract the
      polysaccharide from Zagros oak (Quercus brantii Lindl). The effects of four
      independent factors (ultrasonic power (X1: 150-300 W), extraction temperature
      (X2: 50-90 degrees C), extraction time (X3: 30-90 min), and the ratio of water to
      raw material (X4: 15-45)) on the extraction yield of polysaccharide from the
      leaves of Q. brantii Lindl (QBLP) were optimized using response surface
      methodology. The experimental data obtained were fitted to a second-order
      polynomial equation. The optimal extraction conditions for QBLP were determined
      as follows: X1: 205.8 W, X2: 81.9 degrees C, X3: 55.6 min and X4: 23.4. Under
      these optimal conditions, the experimental yield was 19.42 +/- 0.53%, which was
      well matched with the value predicted by the model 19.61%. The results indicated
      that polysaccharide has strong scavenging activities in vitro on DPPH and
      hydroxyl radicals. In addition, the QBLP showed good antimicrobial activity at
      1.5-2.5mg/mL.

PMID- 24721075
TI  - Structural identification and sulfated modification of an antiglycation
      Dendrobium huoshanense polysaccharide.
AB  - Dendrobium huoshanense, an important food material, has been used to make teas
      and soups in the folk of China for centuries. In the present study, an
      antiglycation polysaccharide DHPD2 with molecular weight of 8.09 * 10(6)Da was
      extracted from the protocorm-like bodies of D. huoshanense. The backbone of DHPD2
      contained (1->5)-linked alpha-l-Araf, (1->6)-linked alpha-d-Glcp, (1->6)-linked
      beta-d-Glcp, (1->4)-linked beta-d-Glcp, (1->3,6)-linked beta-d-Galp and (1->6)
      linked beta-d-Galp, with the branches of terminal alpha-d-Xlyp and beta-d-Manp.
      DHPD2 was further modified using chlorosulfonic acid-pyridine method, giving two
      sulfated derivatives with the substitution degree of 0.475 and 0.940. The
      appearance of two new characteristic absorption bands at near 1250 and 822cm(-1)
      in FT-IR spectra revealed the success of sulfation occurred to DHPD2. Moreover,
      the sulfated derivatives exhibited stronger inhibitory abilities on protein
      glycation than those of DHPD2. NMR analysis disclosed that the sulfation on C2
      and C6 of sugar residues was beneficial to enhance this activity.

PMID- 24721076
TI  - Silane modified starch for compatible reactive blend with poly(lactic acid).
AB  - A reactive blend of poly(lactic acid) (PLA) and a surface modified starch by
      silane coupling agent to achieve compatibility is proposed. A detailed structural
      analysis by using (1)H-(1)H TOCSY NMR spectrum clarifies, for the first time,
      that chloropropyl trimethoxysilane (CPMS) forms covalent bonds with starch during
      starch modification and consequently forms covalent bonds with PLA in the step of
      blending to produce a reactive blend of PLA and CP-starch. The CP-starch
      covalently bound with PLA provides the compatibility between PLA and starch and
      also plays the role as nucleating agent as identified from a significant increase
      of degree of crystallinity (as high as 10-15 times), as well as induces chain
      mobility, as identified from a slight decrease in glass transition temperature
      (~5-10 degrees C). The PLA/CP-starch film performed as well as neat PLA with
      slight increases in tensile strength and elongation at break, as compared to
      other PLA/silane modified starch films.

PMID- 24721077
TI  - Bacterial cellulose membranes as transdermal delivery systems for diclofenac: in
      vitro dissolution and permeation studies.
AB  - Bacterial cellulose (BC) membranes were explored as novel nanostructured
      transdermal delivery systems for diclofenac sodium salt (a typical non-steroidal
      anti-inflammatory drug). Diclofenac sodium salt loaded BC membranes were prepared
      through a simple methodology, using glycerol as plasticizer, and characterized in
      terms of structure, morphology and swelling behavior. The membranes were very
      homogeneous, quite flexible and presented a considerably higher swelling behavior
      when compared with pure BC. In vitro diffusion studies with Franz cells, were
      conducted using human epidermal membranes, and showed that the incorporation of
      diclofenac in BC membranes provided similar permeation rates to those obtained
      with commercial patches and substantially lower than those observed with a
      commercial gel. This release profile together with the ease of application and
      the simple preparation and assembly of the drug-loaded membranes clearly
      indicates the enormous potentialities of using BC membranes for transdermal
      administration of diclofenac. 

PMID- 24721078
TI  - Structure and properties of a (1->3)-beta-D-glucan from ultrasound-degraded
      exopolysaccharides of a medicinal fungus.
AB  - A high molecular weight (MW) exopolysaccaride (EPS) fraction EPS1 was isolated
      from the fermentation broth of a medicinal fungus Cordyceps sinensis Cs-HK1 and
      partially degraded by high-intensity ultrasound (US) into a lower MW fraction
      EPS1U. EPS1U exhibited a single, symmetric peak on size exclusion chromatography
      with an average MW of 730kDa by light scattering analysis. It had a much lower
      intrinsic viscosity (1.7 versus 15.6dL/g) but a much higher solubility in water
      (77.5 versus 5.1g/L) than EPS1. Based on methylation analysis and NMR
      spectrometry, the structure of EPS1U was deduced as a (1->3)-beta-d-glucan with
      glucose side chains attached to O-6 position at the branching points. EPS1U
      showed a high moisture absorption capability comparable to chitosan and urea,
      suggesting its potential as a moisturizing agent for food and cosmeceutical
      application. This is the first report on a high MW (1->3)-beta-d-glucan isolated
      from EPS produced by Cordyceps sinensis.

PMID- 24721079
TI  - A new guar gum-based adsorbent for the removal of Hg(II) from its aqueous
      solutions.
AB  - Modification of biopolymers by oxidation is an easy process to develop effective
      adsorbents for the removal of toxic metal ions from their aqueous solutions. In
      the present study, guar gum (GG) was crosslinked with epichlorohydrin and then
      oxidized to the polydialdehyde form (GG-clPDA). The latter was converted to a
      Schiff-base, GG-clCHN(CH2)6NCHGG, by reaction with hexamethylenediamine.
      Different forms of the modified GG were characterized by SEM, FTIR and XRD and
      investigated as adsorbents for the removal of Hg(II) ions from their aqueous
      solutions. The adsorption process was carried out through the variation of time,
      temperature, pH and initial concentration of Hg(II) ions. GG-clCHN(CH2)6NCHGG was
      observed to be an efficient adsorbent with a maximum adsorption capacity of 41.13
      mg/g. It is reusable up to five cycles at the optimum conditions obtained for the
      maximum ions uptake. The kinetic data generated fit the Freundlich isotherm and
      pseudo-second order kinetics.

PMID- 24721080
TI  - Modifying the flocculation of microfibrillated cellulose suspensions by soluble
      polysaccharides under conditions unfavorable to adsorption.
AB  - Carboxymethylcellulose (CMC) and xanthan gum were studied as dispersants for
      microfibrillated cellulose (MFC) suspension using a rotational rheometer and
      imaging methods. The imaging was a combination of photography and optical
      coherence tomography (OCT). Both polymers dispersed MFC fibers, although CMC was
      more effective than xanthan gum. The negatively charged polymer chains increased
      the viscosity of the suspending medium and acted as buffers in between the
      negatively charged fibers. This behavior decreased the number and strength of
      contacts between the fibers and subsequently dispersed the flocs. The stronger
      separation of the fibers was reflected in the frequency sweep where the
      MFC/polymer suspensions had lower gel strength than pure MFC suspension.
      Dispersing effect was also observed in the flow measurements, where the floc size
      was more uniform with polymers in the decelerating flow and after long, slow
      constant shear, which normally induces a heterogeneous structure with large flocs
      into the MFC suspension.

PMID- 24721082
TI  - Immunopotentiating properties of extracellular polysaccharide from Trametes
      hirsuta strain VKESR.
AB  - The effectiveness of extracellular polysaccharides isolated from Trametes hirsuta
      strain VKESR was evaluated for their immunostimulating properties by in vitro
      lymphocyte proliferation, phagocytic assay, NK cell activity and cytokine
      quantification. The splenocyte proliferation assay showed that the extracellular
      glucans found to have good stimulation index and enhances the NK cell mediated
      tumor killing. It promotes phagocytosis in treated macrophages in a dose
      dependent manner. Furthermore, the polysaccharides exhibit significant
      stimulatory effect on cytokines IL-2 and IFN-gamma whereas the polysaccharide has
      moderate stimulatory effect pro-inflammatory cytokine TNF-alpha. These
      immunostimulating properties help in combating various diseases and could be a
      promising beginning for further research to study the role of extracellular
      polysaccharide on the host immune systems.

PMID- 24721081
TI  - Antioxidant activities of the oligosaccharides from the roots, flowers and leaves
      of Panax ginseng C.A. Meyer.
AB  - The chemical characterization and antioxidant activities of water-soluble ginseng
      oligosaccharides from roots (WGOS-R), flowers (WGOS-F) and leaves (WGOS-L) of
      Panax ginseng C.A. Meyer obtained by hot water extraction were investigated. The
      sugar content of WGOS-R, WGOS-F and WGOS-L were 95.87%, 87.07% and 83.09%,
      respectively. The ginsenosides and total phenols content decreased in the order
      of WGOS-L>WGOS-F>WGOS-R. WGOS-R comprised only Glc, WGOS-F and WGOS-L comprised
      Glucose (Glc) and Rhamnose (Rha) in a molar ratio of 6.0:1.0 and 7.0:1.0,
      respectively. In vitro antioxidant tests showed that WGOS-R exhibited higher
      antioxidant activity than WGOS-F and WGOS-L. In vivo antioxidant tests showed
      that WGOS-R significantly enhanced activities of superoxide dismutase (SOD),
      catalase (CAT), glutathione peroxidase (GSH-Px) and total antioxidant capability
      (T-AOC) in the serum and liver and decreased malondialdehyde (MDA) level in the
      serum and liver.

PMID- 24721083
TI  - Thermal and electrical properties of starch-graphene oxide nanocomposites
      improved by photochemical treatment.
AB  - Bionanocomposite films have been prepared by casting an aqueous suspension of
      acetylated starch (ST) and poly(vinyl alcohol) (PVA) loaded with graphene oxide
      (GO). A photochemical and reagentless method has been successfully performed to
      convert the GO phase into reduced graphene oxide (RGO). The nanocomposites have
      displayed improved thermal and electrical properties when the amount of the GO
      phase is increased and properly converted to RGO. The molecular-level
      interactions between components are mainly hydrogen-bonding type according to
      attenuated total reflectance-Fourier transform infrared (ATR-FTIR) and Raman
      spectroscopies, as well as thermogravimetric analysis (TGA). Scanning electron
      microscopy (SEM) has confirmed the effective mixing between the GO and the ST-PVA
      matrix. The thermal diffusivity and electrical resistivity of ST-GO
      nanocomposites have increased one order and decreased two orders of magnitude,
      respectively, after the photochemical treatment. These findings have confirmed
      the effectiveness of the proposed approach to produce starch-based nanocomposites
      with improved thermal and electrical properties. 

PMID- 24721084
TI  - Preparation and characterization of in-situ crosslinked pectin-gelatin hydrogels.
AB  - Crosslinked hydrogels were developed by in-situ reaction of periodate oxidized
      pectin (OP) and gelatin. The reaction takes place through the formation of Schiff
      bases between aldehyde groups of OP and amino groups of gelatin. The effect of
      various process parameters such as reaction time, reaction temperature, pH of the
      reaction and composition on the efficacy of the crosslinking was investigated.
      Field emission scanning electron micrsocopy (FESEM) revealed that homogenous,
      single phase systems are obtained after the crosslinking of OP and gelatin. The
      swelling characteristics of the hydrogels were monitored. The equilibrium
      swelling varies in the range of 195-324% with a variation in the gelatin content
      (10-40%). Glycerol, when used as a plasticizer, improved the flexibility and the
      handling characteristics of the crosslinked hydrogels. Plasticized films retained
      good tensile strengths in the range of 19-48 MPa. By proper selection of the
      reaction conditions, the efficiency of crosslinking can be controlled to obtain
      the optimum results.

PMID- 24721085
TI  - Antimicrobial fabrication of cotton fabric and leather using green-synthesized
      nanosilver.
AB  - This study aims to investigate the green synthesis of silver nanoparticles
      (AgNPs) by Erigeron annuus (L.) pers flower extract as reducing and capping
      agent, and evaluation of their antibacterial activities for the first time. The
      obtained product was confirmed by UV-Vis spectrum, high resolution-transmission
      electron microscopy, energy-dispersive X-ray spectroscopy, Fourier transform
      infrared spectroscopy, and X-ray diffraction studies. The optimum AgNPs
      production was achieved at pH 7, metal silver (Ag(+) ion) concentration of 2.0mM,
      flower extract concentration 4%, and time 335 min. In addition, the antibacterial
      activity of cotton fabrics and tanned leather loaded with AgNPs, commercial
      AgNPs, flower extract, Ag(+) ion and blend of flower extract with AgNPs were
      evaluated against Gram-positive odor causing bacteria Brevibacterium linens and
      Staphylococcus epidermidis. The results showed maximum zone of inhibition (ZOI)
      by the cotton fabrics embedded with blend of flower extract and AgNPs against B.
      linens. The structure and morphology of cotton fabric and leather samples
      embedded with AgNPs, Ag(+) ion and blend of flower extract with AgNPs were
      examined under field emission scanning electron microscope.

PMID- 24721086
TI  - Bionanocomposites of regenerated cellulose/zeolite prepared using environmentally
      benign ionic liquid solvent.
AB  - Bionanocomposite films based on regenerated cellulose (RC) and incorporated with
      zeolite at different concentrations were fabricated by dissolving cellulose in 1
      ethyl-3-methylimidazolium chloride (EMIMCl) ionic liquid using a simple green
      method. The interactions between the zeolite and the cellulose matrix were
      confirmed by Fourier transform infrared spectra. Mechanical properties of the
      nanocomposite films significantly improved as compared with the pure regenerated
      cellulose film, without the loss of extensibility. Zeolite incorporation enhanced
      the thermal stability and char yield of the nanocomposites. The scanning electron
      microscopy and transmission electron microscopy showed that zeolite was uniformly
      dispersed in the regenerated cellulose matrix. In vitro cytotoxicity test
      demonstrated that both RC and RC/zeolite nanocomposite films are cytocompatible.
      These results indicate that the prepared nanocomposites have potential
      applications in biodegradable packaging, membranes and biomedical areas.

PMID- 24721087
TI  - Purification, characterization and immunomodulating activity of a polysaccharide
      from flowers of Abelmoschus esculentus.
AB  - A water-soluble polysaccharide (OFPS11) was obtained from okra (Abelmoschus
      esculentus) flowers using aqueous extraction and purification with DEAE-52
      cellulose and SephacrylTM S-500 column. Its preliminary characterization and
      immunomodulating activity were investigated. Results showed that OFPS11 is mainly
      composed of galactose and rhamnose in a molar ratio of 2.23:1 with molecular mass
      of 1,700 kDa. RAW264.7 cells pretreated with OFPS11 significantly inhibited the
      proliferation of HepG-2 cells. Additionally, OFPS11 enhanced the phagocytic
      ability and induced the elevation of NO production, TNF-alpha and IL-1beta
      secretion of RAW264.7 cells. Furthermore, OFPS11 promoted both the expression of
      iNOS protein and of iNOS and TNF-alpha mRNA. OFPS11 can strongly increase NF
      kappaB levels in nucleuses, which is an important transcription factor that can
      modulate expressions of iNOS, NO and TNF-alpha. These outcomes support that
      OFPS11 exerts its antitumor activity by probably stimulating macrophage
      activities through nuclear NF-kappaB pathway.

PMID- 24721088
TI  - Quantitative analysis of anions in glycosaminoglycans and application in heparin
      stability studies.
AB  - The sulfo groups of glycosaminoglycans contribute to their high charge densities,
      and are critical for the role they play in various physiological and
      pathophysiological processes. Unfortunately, the sulfo groups can be hydrolyzed
      to inorganic sulfate. Thus, it is important to monitor the presence of these
      sulfo groups. In addition, free anions, including chloride, sulfate and acetate,
      are often present in glycosaminoglycans as a result of multiple purification
      steps, and their presence also needs to be monitored. In this report, ion
      chromatography with conductivity detection is used to analyze the anions present
      in glycosaminoglycans, including heparin, heparan sulfate, chondroitin sulfate
      and dermatan sulfate. This method allows quantitation over a wide range of
      concentrations, affording a limit of quantitation of 0.1 ppm and a limit of
      detection of 0.05 ppm for most anions of interest. The stability of heparin was
      also studied, providing data on the formation of both sulfate and acetate anions.

PMID- 24721089
TI  - CNWs loaded poly(SA) hydrogels: effect of high concentration of CNWs on water
      uptake and mechanical properties.
AB  - In this work, poly(sodium acrylate) (poly(SA)) hydrogel films, doped with
      cellulose nano-whiskers (CNWs), are prepared via free radical polymerization of
      sodium acrylate (SA) in aqueous medium. The CNWs were added into the
      polymerization feed mixture, in the concentration range of 4.8-24.3 wt% of
      monomer and the resulting CNWs/poly(SA) hydrogel films were investigated for
      their water absorbency in the physiological fluid (PF). The addition of CNWs
      caused a decrease in the equilibrium water uptake. The kinetic water uptake data
      of all hydrogel samples were best interpreted by the second order kinetic. The
      water vapor permeation studies were also carried out. The water vapor
      transmission rate (WVTR) of all the film samples was quite low. The mechanical
      properties of films such as tensile strength (TS) and percent elongation (PE)
      varied with the CNWs content. All the film samples showed fair folding endurance
      (FE), with more than 600 times folding without suffering from any crack.

PMID- 24721090
TI  - Preparation and characterization of starch nanoparticles through ultrasonic
      assisted oxidation methods.
AB  - In this work, starch nanoparticles (SNPs) were prepared from waxy corn starch
      (WCS) through ultrasonic-assisted oxidation. Three SNPs samples were produced by
      one time oxidation followed by ultrasonic treatment (O1U1-SNPs), twice oxidation
      and twice ultrasonic treatment (O2U2-SNPs) and TEMPO-mediated oxidation with
      ultrasonic treatment (TEMPO-SNPs), respectively. Differential scanning
      calorimetry (DSC), X-ray diffraction analysis (XRD), scanning electron microscopy
      (SEM) and Fourier transform infrared (FTIR) spectroscopy were used to
      characterize the thermal properties, morphology, and structure of the ensuing
      nanoparticles. The results revealed that the size of the O1U1-SNPs, O2U2-SNPs,
      and TEMPO-SNPs particles reached 30-50 nm, 20-50 nm and 20-60 nm, respectively.
      Compared to WCS, the crystallinity of the O1U1-SNPs, O2U2-SNPs and TEMPO-SNPs
      samples decreased from 36.32% to 11.35%, 1.64% and 1.72%, respectively. The O1U1
      SNPs, O2U2-SNPs and TEMPO-SNPs exhibited smaller or no endotherms. The SNPs had
      higher carboxyl and carbonyl content.

PMID- 24721091
TI  - Modification of agarose: 6-aminoagarose mediated syntheses of fluorogenic
      pyridine carboxylic acid amides.
AB  - A facile 6-aminoagarose (AA) mediated synthesis of new fluorogenic amides of
      agarose with nicotinic (AA-NA) and picolinic acids (AA-PA) employing carbodiimide
      chemistry have been described. 6-Amino agarose (AA) was synthesized in a facile
      Mitsunobu-inspired microwave mediated method involving the reaction of agarose
      with phthalimide in presence of diisopropyl azodicarboxylate and
      triphenylphosphene (DIAD/TPP) followed by hydrazinolysis. All compounds were
      characterized by GPC, UV spectrophotometry, fluorescence spectroscopy, FT-IR,
      (1)H and (13)C NMR spectra. The fluorescence emissions (lambdamax 430 and 412 nm)
      of 1 * 10(-3)M solutions of AA-NA and AA-PA in water were significantly higher
      (ca. 82% and ca. 90%) than those of the molar equivalents (0.2mg) of NA and PA
      present in the 1 * 10(-3)M solutions of the amides, respectively. These
      fluorogenic pyridine carboxylic acid amides of agarose may find applications as
      sensors in biomedical and pharmaceutical industries.

PMID- 24721092
TI  - Fractionation of Eremurus spectabilis fructans by ethanol: Box-Behnken design and
      principal component analysis.
AB  - The fructans, inulin and oligofructose, are known to exert many food and
      pharmaceutical applications and are widely used in functional foods throughout
      the world for their nutritional and techno-functional properties. In the present
      study, the Box-Behnken design was used to determine the optimal conditions for
      fructan precipitation from Eremurus spectabilis root powder (Serish) by adding
      ethanol that gave the maximum yield. Ethanol-to-syrup (E/S) ratio (2:1-15:1),
      precipitation temperature (30-60 degrees C) and syrup concentration (10-40
      degrees B) were considered variables of fructan precipitation. The most
      compatible model among mean, linear and quadratic expressions was fitted to each
      response and the regression coefficients were determined using least square
      method. There was a good agreement between the experimental data and their
      predicted counterparts. The optimum conditions for fractionating fructan
      composition of Serish by ethanol were estimated to be E/S ratio of 8.56,
      temperature of 23.51 degrees C and initial syrup concentration of 40 degrees B.
      Precipitation under these optimized conditions achieved the best yield (85.81%),
      average chain length (12.92) and purity (80.18%). In addition, principal
      component analysis (PCA) allowed discriminating among precipitated fructan
      specialties.

PMID- 24721093
TI  - Structural investigation of a neutral extracellular glucan from Lactobacillus
      reuteri SK24.003.
AB  - The structural features of a neutral extracellular glucan derived from
      Lactobacillus reuteri SK24.003 were investigated. Colonies of the strain SK24.003
      exhibited a creamy and slimy morphological appearance on MRS solid medium and
      were identified as L. reuteri via 16S rDNA sequence analysis. The
      exopolysaccharide produced from sucrose was composed exclusively of glucose, and
      the weight-average molecular weight was 4.31 * 10(7)g/mol. The polysaccharide
      exhibited an alpha-(1->4) backbone with an alpha-(1->6) branch at every fourth
      residue, as deduced from both NMR and GC-MS data. The exopolysaccharide acted as
      a natural steel corrosion inhibitor. The results suggested that a novel alpha
      glucan produced by L. reuteri SK24.00 could be broadly used in food and material
      field.

PMID- 24721094
TI  - Jellyfish skin polysaccharides: extraction and inhibitory activity on macrophage
      derived foam cell formation.
AB  - In this work, response surface methodology was used to determine optimum
      conditions for extraction of polysaccharides from jellyfish skin (JSP). The
      optimum parameters were found to be raw material to water ratio 1:7.5 (w/v),
      extraction temperature 100 degrees C and extraction time 4h. Under these
      conditions, the JSP yield reached 1.007 mg/g. Papain (15 U/mL) in combination
      with Sevag reagent was beneficial in removing proteins from JSP. After
      precipitation with ethanol at final concentration of 40%, 60% and 80% in turn,
      three polysaccharide fractions of JSP1, JSP2 and JSP3 were obtained from JSP,
      respectively. The three fractions exhibited different physicochemical properties
      with respect to molecular weight distribution, monosaccharide composition,
      infrared absorption spectra, and glycosyl bond composition. In addition, JSP3
      showed strong inhibitory effects on oxidized low-density lipoprotein (oxLDL)
      induced conversion of macrophages into foam cells, which possibly attributed to
      the down-regulation of some atherogenesis-related gene expressions.

PMID- 24721095
TI  - Preparation and properties of PEC nanocomposite membranes with carboxymethyl
      cellulose and modified silica.
AB  - Carboxymethyl cellulose (CMC)-modified silica nanocomposites were prepared via in
      situ incorporation of modified silica during the ionic complexation between CMC
      and poly(2-methacryloyloxy ethyl trimethylammonium chloride) (PDMC). Ionic bonds
      were introduced between the poly(2-acrylamido-2-methylproanesulfonic acid)
      modified silica (SiO2-PAMPS) and the polyelectrolyte complex (PEC) matrix. The
      PEC nanocomposites (PECNs) and their membranes (PECNMs) were characterized with
      Fourier transform-infrared spectroscopy (FT-IR), thermogravimetric analysis
      (TGA), scanning electron microscopy (SEM) and tensile testing. PECNM containing 5
      wt.% SiO2-PAMPS showed a tensile strength of 68 MPa and elongation at break of
      7.1%, which were 1.9 and 2.6 times as high as those of pristine PEC membranes,
      respectively. Moreover, the pervaporation performance of as-prepared PECNMs was
      evaluated with dehydration of 10 wt.% aqueous isopropanol mixtures, and the
      PECNMs exhibited a flux of 2,400 gm(-2)h(-1) with a high separation factor of
      4491 at 70 degrees C.

PMID- 24721096
TI  - Loading of bacterial nanocellulose hydrogels with proteins using a high-speed
      technique.
AB  - For the loading of the natural biopolymer bacterial nanocellulose (BNC) with
      drugs, usually an adsorption method has been described. In the present study, a
      high-speed loading technique based on vortexing was established for the
      incorporation of proteins in BNC as drug delivery system. Compared to the
      conventional technique, vortexing accomplished in 10 min the same protein loading
      capacity as the adsorption method in 24h with comparable protein distribution and
      protein stability. Vortex loaded BNC demonstrated a retarded protein release with
      a lower total amount of released protein after 168 h compared to the adsorption
      loaded BNC. This was correlated with a densification of the fiber network as
      shown by electron microscopy and a reduced water holding capacity. These
      observations offer the possibility to control the drug release by selection of
      the preparation technique.

PMID- 24721097
TI  - Effect of ionic crosslink on the release of metronidazole from partially
      carboxymethylated guar gum tablet.
AB  - Partially carboxymethylated guar gum (PCMGG) was crosslinked in situ by Ca(2+)
      ions during wet massing step of tablet preparation. The resulting tablets were
      evaluated for the effect of the extent of crosslinking on drug release and matrix
      swelling. Increase in the concentration of Ca(2+) ions increased the viscosity of
      gel layer and reduced the water penetration velocity into the matrix with
      subsequent decrease in swelling of the tablets and drug release. Beyond a certain
      concentration of Ca(2+) ions, the viscosity of the gel layer decreased and the
      drug release rate increased primarily due to erosion of the matrix. The mechanism
      of drug release appeared to be non-Fickian or anomalous transport. The release
      data also best fitted in zero order equation. The model drug, metronidazole, was
      compatible with the matrix materials as evident from instrumental analyses. Such
      formulation may provide flexibility in achieving the desired drug release rate
      from crosslinked matrix tablets.

PMID- 24721098
TI  - Azo dye/cyclodextrin: new findings of identical nanorods through 2:2 inclusion
      complexes.
AB  - Inclusion complexation behavior of 4-aminoazobenzene (AAB) and 4-amino-2,3'
      dimethyl azobenzene (GBC, fast grant GBC) with alpha- and beta-cyclodextrins
      (alpha-CD, beta-CD) is analyzed by scanning electron microscope, transmission
      electron microscope, Fourier transform infrared spectroscopy, differential
      scanning calorimetry, powder X-ray diffraction, and proton nuclear magnetic
      resonance spectroscopy techniques. Transmission electron microscope analysis
      suggests that identical nanorods formed in AAB/CD inclusion complexes while
      different dimension nanostructures were observed in GBC/CD inclusion complexes.
      The nanostructures confirmed that the ratio of 2:2 (guest:host) inclusion complex
      has been developed to a miniature nanorod. Nanosecond time-resolved fluorescence
      studies indicated that AAB/GBC have fast life time in water, whereas slow life
      time in CDs corresponds to a higher-order structure of 2:2 complexes.
      Thermodynamic parameters and binding affinity of the inclusion complex formation
      were determined and discussed. van der Waals interactions are mostly responsible
      for enthalpy-driven complex formation of AAB and GBC with cyclodextrins. 

PMID- 24721099
TI  - Starch-based nanocomposites: a comparative performance study of cellulose
      whiskers and starch nanoparticles.
AB  - A comparative performance study of cellulose whiskers (CW) and starch
      nanoparticles (SN) on plasticized starch (PS) reinforcement has been presented.
      In order to study the involved surface phenomena, CW and SN were extracted
      through acid hydrolysis using sulfuric acid to fulfill the similar surface groups
      and interactions. CW-filled and SN-filled nanocomposites were then prepared with
      relatively identical process to alleviate the effect of fabrication method for
      better comparison of CW and SN performance on PS reinforcement. Morphology of
      nanoparticles and their dispersion state in the corresponding nanocomposites were
      investigated by transmission electron microscopy and field emission scanning
      electron microscopy, respectively. X-ray diffraction was used for crystallography
      of nanocomposites and established the transcrystallization only in CW-filled
      nanocomposites. Nanocomposites comprising quasi-spherical SNs showed higher
      reinforcement in dynamic mechanical tests compared to the corresponding
      nanocomposites containing rod-like CWs, which were attributed to more efficient
      filler/filler and filler/matrix interactions originated from hydrogen bonding in
      SN-filled nanocomposites. 

PMID- 24721100
TI  - Microwave-assisted graft copolymerization of amino acid based monomers onto
      starch and their use as drug carriers.
AB  - This paper describes the synthesis of two amino acid-based monomer and their
      graft copolymerization onto starch and utilization of the prepared graft
      copolymers as drug carriers. The two monomers were synthesized and reacted with
      acryloyl chloride to get the corresponding acryloylamino acid, which were further
      grafted onto starch using the microwave-assisted grafting technique. All factors
      affecting the efficiency of the grafting reaction were studied and the prepared
      graft copolymers were fully characterized. Atenolol, as a model drug in the form
      of salt was immobilized onto the graft copolymers by ionic bonds and the loading
      was confirmed by use of FT-IR, TGA and NMR. The drug release was studied in both
      acidic and alkaline media and it was found that the release takes place in
      alkaline medium rather than in acidic medium and this indicates that these
      polymers can be used as carriers for drugs whose target is the colon. 

PMID- 24721101
TI  - Densitometry and ultrasound velocimetry of hyaluronan solutions in water and in
      sodium chloride solution.
AB  - The densities of hyaluronan solutions in water and 0.15M NaCl were measured in
      the temperature range from 25 to 50 degrees C for the hyaluronan molecular
      weights from 10 to 1,750 kDa. The density increased linearly with concentration
      and decreased with temperature. The data were fitted by the equation describing
      the density as a linear function of concentration and a quadratic function of
      temperature. The effect of molecular weight was negligible and thus single
      equation was sufficient to describe all data. The apparent and partial specific
      volumes were calculated from the density data including their extrapolated values
      to infinite dilutions. The measurement of ultrasound speed in the same solutions
      under the same conditions enabled to calculate the compressibility and its
      dependence on concentration and temperature. The compressibility decreased with
      both the concentration and the temperature but the effect of the concentration
      was only slight mild. The compressibility was used to estimate the hydration
      numbers which slightly decreased with increasing temperature and concentration.
      The addition of NaCl changed only the numerical values of density and ultrasound
      velocity while not changing the character of their dependence on temperature and
      concentration. Measured and calculated data indicate that hyaluronan does not
      disturb the specific water structure in the studied concentration range and
      support the idea of the existence of water clusters or nanodroplets hydrating the
      hyaluronan chains in solution.

PMID- 24721102
TI  - The Yariv reagent: behaviour in different solvents and interaction with a gum
      arabic arabinogalactan-protein.
AB  - The beta-D-Glc Yariv reagent is frequently used to isolate and to study the
      structure of arabinogalactan-proteins with the arabinogalactan type II structure.
      The present paper describes the aggregation features of the Yariv reagent in
      water, salt solutions and in organic solvents as determined by NMR, absorption
      spectroscopy and light scattering experiments. The results indicate that in water
      the Yariv reagent forms aggregates of up to 300 units and in 1% aqueous NaCl the
      degree of aggregation is approx. 150. The aggregates are formed both by H-bonds
      and hydrophobic interactions, the former appearing to be of most importance in
      water. The interaction between the Yariv reagent and an AGP fraction from gum
      arabic, showed a degree of aggregation of the Yariv reagent when using 1% NaCl to
      be of approx. 150 units, whereas disruption of the aggregate took place in 10%
      NaCl with an aggregation number of approx. 100. Partial acid hydrolysis of an AGP
      from gum Arabic (Acacia Senegal) and analyses of the linkage types remaining
      indicated that a certain length of (1->3)-beta-linked galactose units was
      necessary for binding between the Yariv reagent and the AGP. This is in
      accordance to what also was recently observed by Kitazawa et al. (2013).

PMID- 24721103
TI  - Completely green synthesis of dextrose reduced silver nanoparticles, its
      antimicrobial and sensing properties.
AB  - We herein report the green synthesis of highly monodispersed, water soluble,
      stable and smaller sized dextrose reduced gelatin capped-silver nanoparticles (Ag
      NPs) via an eco-friendly, completely green method. The synthesis involves the use
      of silver nitrate, gelatin, dextrose and water as the silver precursor,
      stabilizing agent, reducing agent and solvent respectively. By varying the
      reaction time, the temporal evolution of the growth, optical, antimicrobial and
      sensing properties of the as-synthesised Ag-NPs were investigated. The
      nanoparticles were characterized using UV-vis absorption spectroscopy, Fourier
      transform infra-red spectroscopy (FT-IR), X-ray diffraction (XRD), transmission
      electron microscopy (TEM) and high resolution transmission electron microscopy
      (HR-TEM). The absorption maxima of the as-synthesized materials at different
      reaction time showed characteristic silver surface plasmon resonance (SPR) peak.
      The as-synthesised Ag-NPs show better antibacterial efficacy than the
      antibiotics; ciproflaxin and imipenem against Pseudomonas aeruginosa with minimum
      inhibition concentration (MIC) of 6 MUg/mL, and better efficacy than imipenem
      against Escherichia coli with MIC of 10 MUg/mL. The minimum bactericidal
      concentration (MBC) of the as-synthesised Ag-NPs is 12.5 MUg/mL. The sensitivity
      of the dextrose reduced gelatin-capped Ag-NPs towards hydrogen peroxide indicated
      that the sensor has a very good sensitivity and a linear response over wide
      concentration range of 10(-1)-10(-6)M H2O2.

PMID- 24721104
TI  - Optimization of upper gastrointestinal endoscopy: value of real-time gastric
      juice analysis.

PMID- 24721105
TI  - The role of (18)fluoro-deoxyglucose positron emission tomography/computed
      tomography in resectable pancreatic cancer.
AB  - BACKGROUND: The role of (18)fluoro-deoxyglucose positron emission
      tomography/computed tomography in pancreatic ductal adenocarcinoma is debated. We
      retrospectively assessed the value of (18)fluoro-deoxyglucose positron emission
      tomography/computed tomography in addition to conventional imaging as a staging
      modality in pancreatic cancer. METHODS: (18)Fluoro-deoxyglucose positron emission
      tomography/computed tomography was performed in 72 patients with resectable
      pancreatic carcinoma after multi-detector computed tomography positron emission
      tomography was considered positive for a maximum standardized uptake value >3.
      RESULTS: Overall, 21% of patients had a maximum standardized uptake value <= 3,
      and 60% of those had undergone neoadjuvant treatment (P=0.0001). Furthermore, 11%
      of patients were spared unwarranted surgery since positron emission
      tomography/computed tomography detected metastatic disease. All liver metastases
      were subsequently identified with contrast-enhanced ultrasound. Sensitivity and
      specificity of positron emission tomography/computed tomography for distant
      metastases were 78% and 100%. The median CA19.9 concentration was 48.8 U/mL for
      the entire cohort and 292 U/mL for metastatic patients (P=0.112). CONCLUSIONS:
      The widespread application of (18)fluoro-deoxyglucose positron emission
      tomography/computed tomography in patients with resectable pancreatic carcinoma
      seems not justified. It should be considered in selected patients at higher risk
      of metastatic disease (i.e. CA19.9>200 U/mL) after undergoing other imaging
      tests. Neoadjuvant treatment is significantly associated with low metabolic
      activity, limiting the value of positron emission tomography in this setting.

PMID- 24721106
TI  - The learning effect of a training programme on the diagnosis of oesophageal
      lesions by narrow band imaging magnification among endoscopists of varying
      experience.
AB  - BACKGROUND: Magnifying narrow-band imaging using intra-epithelial papillary
      capillary loop analysis has been confirmed as a promising diagnostic modality for
      oesophageal lesions. Little is known about its learning curve. AIM: To evaluate
      the effect of a training programme on the diagnosis of oesophageal lesions by
      different modalities among endoscopists of varying experience. METHODS: We
      divided endoscopists into three groups based on their experience. A 2-h training
      programme on magnifying narrow-band imaging and intra-epithelial papillary
      capillary loop patterns was provided to trainees. They evaluated the test images
      and suggested diagnoses both before and after training. Diagnostic accuracy and
      interobserver agreement of three modalities were analysed. RESULTS: The
      diagnostic accuracies of magnifying narrow-band imaging for differentiating
      oesophageal neoplastic lesions and predicting lesion depth were significantly
      improved in less-experienced (92.8% vs. 55.9%, 63.8% vs. 17.5%) and non
      experienced endoscopist groups (84.2% vs. 47.4%, 50% vs. 10%), and kappa (kappa)
      values for both groups achieved good agreement after training (0.76 vs. 0.43,
      0.68 vs. 0.24, respectively), all P<0.05. CONCLUSION: Magnifying narrow-band
      imaging could be learnt easily and rapidly by beginners. For diagnosis of
      oesophageal neoplastic lesions, our training programme improved the diagnostic
      skill of less-experienced endoscopists to the level of highly experienced
      endoscopists.

PMID- 24721107
TI  - One or two operator technique and quality performance of colonoscopy: a
      randomised controlled trial.
AB  - BACKGROUND: The two-operator technique for colonoscopy, with the endoscopy
      assistant actively advancing and withdrawing the scope, is still commonly
      practiced in Europe. As uncontrolled data has suggested that the one-operator
      technique is associated with a higher adenoma detection rate, we tested the
      hypothesis that the two-operator-technique can achieve comparable performances in
      terms of adenoma detection. METHODS: Non-inferiority trial in which consecutive
      adult outpatients were randomised to undergo colonoscopy by one (one-operator) or
      by four endoscopists. Each performed half the procedures by one-operator and half
      by two-operator technique independently of routine clinical practice. Main
      outcome measure was adenoma detection rate. RESULTS: 352 subjects (49% males,
      mean age 60 +/- 12.1 years) were randomised to one (n=176) or to two-operator
      technique (n=176) colonoscopy. No significant differences were found in adenoma
      detection (33% vs. 30.7%, p=0.65), or cecal intubation rate, procedure times, and
      patient tolerability. No differences were found in the subgroup analysis
      according to routinely adopted colonoscopy technique. CONCLUSIONS: This study
      does not confirm a higher adenoma detection rate for one-operator technique
      colonoscopy. Changing current practice to improve adenoma detection rate for
      endoscopists routinely using two-operator technique is not warranted.

PMID- 24721108
TI  - Internet-based guided self-help for glioma patients with depressive symptoms:
      design of a randomized controlled trial.
AB  - BACKGROUND: Among glioma patients, depression is estimated to be more prevalent
      than in both the general population and the cancer patient population. This can
      have negative consequences for both patients and their primary informal
      caregivers (e.g., a spouse, family member or close friend). At present, there is
      no evidence from randomized controlled trials for the effectiveness of
      psychological treatment for depression in glioma patients. Furthermore, the
      possibility of delivering mental health care through the internet has not yet
      been explored in this population. Therefore, a randomized controlled trial is
      warranted to evaluate the effects of an internet-based, guided self-help
      intervention for depressive symptoms in glioma patients. METHODS/DESIGN: The
      intervention is based on problem-solving therapy. An existing 5-week course is
      adapted for use by adult glioma patients with mild to moderate depressive
      symptoms (Center for Epidemiology Studies Depression Scale score >=12). Sample
      size calculations yield 126 glioma patients to be included, who are randomly
      assigned to either the intervention group or a waiting list control group. In
      addition, we aim to include 63 patients with haematological cancer in a non
      central nervous system malignancy control group. Assessments take place at
      baseline, after 6 and 12 weeks, and after 6 and 12 months. Primary outcome
      measure is the change in depressive symptoms. Secondary outcome measures include
      health-related quality of life, fatigue, costs and patient satisfaction. In
      addition, all patients are asked to assign a primary informal caregiver, who does
      not participate in the intervention but who is asked to complete similar
      assessments. Their mood, health-related quality of life and fatigue is evaluated
      as well. DISCUSSION: This is the first study to evaluate the effects of problem
      solving therapy delivered through the internet as treatment for depressive
      symptoms in glioma patients. If proven effective, this treatment will contribute
      to the mental health care of glioma patients in clinical practice. TRIAL
      REGISTRATION: Netherlands Trial Register NTR3223.

PMID- 24721109
TI  - The synthesis of a corrole analogue of aquacobalamin (vitamin B12a) and its
      ligand substitution reactions.
AB  - The synthesis of a Co(III) corrole, [10-(2-[[4-(1H-imidazol-1
      ylmethyl)benzoyl]amino]phenyl)-5,15-diphenylcorrolato]cobalt(III), DPTC-Co,
      bearing a tail motif terminating in an imidazole ligand that coordinates Co(III),
      is described. The corrole therefore places Co(III) in a similar environment to
      that in aquacobalamin (vitamin B12a, H2OCbl(+)) but with a different equatorial
      ligand. In coordinating solvents, DPTC-Co is a mixture of five- and six
      coordinate species, with a solvent molecule occupying the axial coordination site
      trans to the proximal imidazole ligand. In an 80:20 MeOH/H2O solution, allowed to
      age for about 1 h, the predominant species is the six-coordinate aqua species
      [H2O-DPTC-Co]. It is monomeric at least up to concentrations of 60 MUM. The
      coordinated H2O has a pKa = 9.76(6). Under the same conditions H2OCbl(+) has a
      pKa = 7.40(2). Equilibrium constants for the substitution of coordinated H2O by
      exogenous ligands are reported as log K values for neutral N-, P-, and S-donor
      ligands, and CN(-), NO2(-), N3(-), SCN(-), I(-), and Cys in 80:20 MeOH/H2O
      solution at low ionic strength. The log K values for [H2O-DPTC-Co] correlate
      reasonably well with those for H2OCbl(+); therefore, Co(III) displays a similar
      behavior toward these ligands irrespective of whether the equatorial ligand is a
      corrole or a corrin. Pyridine is an exception; it is poorly coordinated by
      H2OCbl(+) because of the sterically hindered coordination site of the corrin.
      With few exceptions, [H2O-DPTC-Co] has a higher affinity for neutral ligands than
      H2OCbl(+), but the converse is true for anionic ligands. Density functional
      theory (DFT) models (BP86/TZVP) show that the Co-ligand bonds tend to be longer
      in corrin than in corrole complexes, explaining the higher affinity of the latter
      for neutral ligands. It is argued that the residual charge at the metal center
      (+2 in corrin, 0 in corrole) increases the affinity of H2OCbl(+) for anionic
      ligands through an electrostatic attraction. The topological properties of the
      electron density in the DFT-modeled compounds are used to explore the nature of
      the bonding between the metal and the ligands. 

PMID- 24721110
TI  - The role of indoleamine 2,3-dioxygenase (IDO) in immune tolerance: focus on
      macrophage polarization of THP-1 cells.
AB  - Macrophages can be divided into two groups as M1 and M2 phenotype. Our results
      and other groups revealed that IFN-gamma can up-regulate the IDO expression and
      differentiate THP-1 cells to M1 phenotype. Therefore we hypothesized that IDO may
      play potential roles in macrophage differentiation. Interesting, our results
      indicated that the ectopic IDO increases the expression of M2 markers such as IL
      10 and CXCR4 while decreases the M1 markers such as CCR7 and IL-12p35. In
      contrast, the knockdown of IDO expression in THP-1 cells resulted in increased M1
      markers and lower M2 markers. Our results suggested that the expression intensity
      of IDO modulates macrophages differentiation. These finding support the counter
      regulatory role for IDO with regarding to the polarization of macrophages to
      restrain excessive or inappropriate immune activation in inflammatory or tumor
      microenvironment. It throws new light on the mechanisms about the
      immunosuppressive effect of IDO in tumor or inflammatory diseases. 

PMID- 24721111
TI  - Dectin-1 activation induces proliferation and migration of human keratinocytes
      enhancing wound re-epithelialization.
AB  - Beta-glucans in temporary wound dressings have immuno-stimulatory capacities and
      have been shown to enhance wound healing in burn patients. Curdlan is a 1,3
      linked bacterial/fungal derived beta-glucan that induces inflammatory responses
      via the C-type lectin receptor dectin-1 on dendritic cells (DCs). Here we
      investigated the effect of beta-glucan curdlan and the role of dectin-1 expressed
      by keratinocytes (KCs) in wound healing. Curdlan enhanced migration,
      proliferation and wound closure of human KCs in a dectin-1 dependent manner, both
      in vitro and ex vivo. Our data suggest that curdlan induces human KC
      proliferation and migration and could therefore be used in creams to enhance
      wound healing. 

PMID- 24721112
TI  - Nutrient regulation of glucagon secretion: involvement in metabolism and
      diabetes.
AB  - Glucose homeostasis is precisely regulated by glucagon and insulin, which are
      released by pancreatic alpha- and beta-cells, respectively. While beta-cells have
      been the focus of intense research, less is known about alpha-cell function and
      the actions of glucagon. In recent years, the study of this endocrine cell type
      has experienced a renewed drive. The present review contains a summary of
      established concepts as well as new information about the regulation of alpha
      cells by glucose, amino acids, fatty acids and other nutrients, focusing
      especially on glucagon release, glucagon synthesis and alpha-cell survival. We
      have also discussed the role of glucagon in glucose homeostasis and in energy and
      lipid metabolism as well as its potential as a modulator of food intake and body
      weight. In addition to the well-established action on the liver, we discuss the
      effects of glucagon in other organs, where the glucagon receptor is expressed.
      These tissues include the heart, kidneys, adipose tissue, brain, small intestine
      and the gustatory epithelium. Alterations in alpha-cell function and abnormal
      glucagon concentrations are present in diabetes and are thought to aggravate the
      hyperglycaemic state of diabetic patients. In this respect, several experimental
      approaches in diabetic models have shown important beneficial results in
      improving hyperglycaemia after the modulation of glucagon secretion or action.
      Moreover, glucagon receptor agonism has also been used as a therapeutic strategy
      to treat obesity. 

PMID- 24721113
TI  - Elucidating the meaning of dipole variability in MEG/MSI.

PMID- 24721114
TI  - Evaluation of the acceptability, feasibility and effectiveness of two methods of
      involving patients with disability in developing clinical guidelines: study
      protocol of a randomized pragmatic pilot trial.
AB  - BACKGROUND: Despite growing interest in the importance of, and challenges
      associated with the involvement of patient and population (IPP) in the process of
      developing and adapting clinical practice guidelines (CPGs), there is a lack of
      knowledge about the best method to use. This is especially problematic in the
      field of rehabilitation, where individuals with disabilities might face many
      barriers to their involvement in the guideline development and adaptation
      process. The goal of this pilot trial is to document the acceptability,
      feasibility and effectiveness of two methods of involving patients with a
      disability (traumatic brain injury) in CPG development. METHODS/DESIGN: A single
      blind, randomized, crossover pragmatic trial will be performed with 20 patients
      with traumatic brain injury (TBI). They will be randomized into two groups, and
      each will try two alternative methods of producing recommendations; a discussion
      group (control intervention) and a Wiki, a webpage that can be modified by those
      who have access to it (experimental intervention). The participants will rate the
      acceptability of the two methods, and feasibility will be assessed using
      indicators such as the number of participants who accessed and completed the two
      methods, and the number of support interventions required. Twenty experts,
      blinded to the method of producing the recommendations, will independently rate
      the recommendations produced by the participants for clarity, accuracy,
      appropriateness and usefulness. DISCUSSION: Our trial will allow for the use of
      optimal IPP methods in a larger project of adapting guidelines for the
      rehabilitation of individuals with TBI. Ultimately the results will inform the
      science of CPG development and contribute to the growing knowledge about IPP in
      rehabilitation settings. TRIAL REGISTRATION: Clinical trial KT Canada 87776.

PMID- 24721115
TI  - Psychosocial interventions for children exposed to traumatic events in low- and
      middle-income countries: study protocol of an individual patient data meta
      analysis.
AB  - BACKGROUND: The burden of mental health and psychosocial problems in children
      exposed to traumatic events in humanitarian settings in low- and middle-income
      countries is substantial. An increasing number of randomized studies has shown
      promising effects of psychosocial interventions, but this evidence has shown
      complexity with regard to setting, conflict-phase, gender, and age. These complex
      findings raise the need of a detailed evaluation of the specific factors which
      influence size and direction of intervention effects.Individual patient data meta
      analysis is a specific type of meta-analysis that allows the collection of exact
      information at an individual patient level, and to examine whether intervention
      and socio-demographic characteristics, trauma-related variables, environmental
      conditions, and social support may act as moderators and mediators of
      intervention effect.The aim of the present study is to carry out an individual
      patient data meta-analysis using data from all available randomized controlled
      trials (either published or unpublished) comparing psychosocial intervention with
      waiting list or no intervention arms in children exposed to traumatic events
      living in low- and middle-income countries. METHODS/DESIGN: All randomized trials
      comparing selective preventive psychosocial intervention versus waiting list or
      no treatment conditions in children (0-18 years) living in low- and middle-income
      countries will be included. Studies will be identified in accordance with the
      Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines.
      There will be no restrictions on publication type, status, language, or date of
      publication. The primary outcome measures will be psychological symptoms (post
      traumatic stress disorder, anxiety, depression). Secondary outcomes will be
      positive mental health outcomes (coping methods, social support, self-esteem),
      and function impairment. DISCUSSION: We are expecting that some variables, like
      socio-demographic characteristics, trauma-related variables, environmental
      conditions, and social support will act as moderators/mediators of intervention
      effect. The investigation of the role of these factors on the intervention
      effects will help in the appropriate selection, development, implementation, and
      dissemination of evidence-based programs in low- and middle-income countries.
      TRIAL REGISTRATION: This protocol has been registered with the International
      Prospective Register of Systematic Reviews (PROSPERO) (registration number:
      CRD42013006960).

PMID- 24721116
TI  - Ba2HgS5--a molecular trisulfide salt with dumbbell-like (HgS2)2- ions.
AB  - Ba2HgS5 was synthesized by cooling a molten mixture of BaS, HgS, and elemental
      sulfur. It crystallizes in the orthorhombic Pnma space group with a = 12.190(2)
      A, b = 8.677(2) A, c = 8.371(2) A, and dcalc = 4.77 g cm(-3). Its crystal
      structure consists of isolated dumbbell-shaped (HgS2)(2-) and v-shaped S3(2-)
      ions. These molecular anions are charge-balanced by Ba(2+) cations. Raman
      spectroscopy shows three strong bands originating from symmetric, asymmetric, and
      bending vibrational modes of the S3(2-) ions. X-ray photoelectron spectroscopic
      analysis confirms the presence of the trisulfide species. Ba2HgS5 has a bandgap
      of ~2.4 eV. Electronic band structure calculations show that the bandgap is
      defined essentially by the p-orbitals of the sulfur atoms of the S3(2-) group. 

PMID- 24721117
TI  - Heterogeneity in coal composition and implications for lung cancer risk in
      Xuanwei and Fuyuan counties, China.
AB  - BACKGROUND: Xuanwei and Fuyuan counties in Yunnan Province, China have among the
      highest lung cancer rates in the country. This has been associated with the
      domestic combustion of bituminous coal (referred to as "smoky" coal).
      Additionally, significant geographical variation in cancer rates among smoky coal
      users has been observed, suggesting heterogeneity in fuel source composition
      and/or combustion characteristics. Research thus far has indicated that smoky
      coal emits high levels of polycyclic aromatic hydrocarbons (PAHs) and contains
      high concentrations of fine grained crystalline quartz, however, much of this
      research is limited in terms of sample size and geographic scope. In order to
      more fully characterise geochemical and elemental compositions of smoky and
      smokeless coal use in Xuanwei and Fuyuan, we carried out a large exposure
      assessment study in households in this region. METHODS: Fuel samples representing
      smoky and "smokeless" (anthracite, the major alternative coal type in the region)
      coals were collected from 137 homes in Xuanwei and Fuyuan. Rock-Eval, Leco-CS,
      XRF analysis and electron microscopy were used to establish hydrocarbon content
      (to represent volatile organic compounds), major and trace element composition
      and mineral composition respectively. Heterogeneity in coal characteristics
      between and within coal types was assessed by the Kruskal-Wallis test. RESULTS:
      145 coal samples (116 smoky and 29 smokeless coals) were analysed. Statistically
      significant differences between smoky and smokeless coals with regard to
      hydrocarbon content, sulfur, trace elements and mineral composition were
      observed. Of note, smoky coal contained between 5 and 15 times the amount of
      volatile organic matter and twice the amount of quartz (including respirable
      quartz) than smokeless coal. Smoky coal generally had lower levels of trace
      elements (plus aluminium) than smokeless coal. Significant variation was also
      observed between smoky coal samples from different geographical areas with regard
      to hydrocarbon content and elemental composition (including aluminium and
      silicon). DISCUSSION: This paper has identified compositional differences between
      and within smoky and smokeless coals sourced from Xuanwei and Fuyuan counties. A
      decreased ratio of aluminium to silicon in smoky coal suggests elevated free
      silica, a finding consistent with observed higher levels of quartz. Elevated
      volatile organic matter content in smoky coal (when compared to smokeless coal)
      is consistent with the geochemical expectations for smoky and smokeless coals.
      These findings also reflect previous observations of elevated volatile compound
      emissions (notably PAHs) from smoky coal in the area. The observed heterogeneity
      in coal composition between and within coal types may provide leads to the
      observed heterogeneity in cancer risk observed in this area.

PMID- 24721118
TI  - Simulation of CO2 leakages during injection and storage in sub-seabed geological
      formations: metal mobilization and biota effects.
AB  - To assess the potential effects on metal mobilization due to leakages of CO2
      during its injection and storage in marine systems, an experimental set-up was
      devised and operated, using the polychaete Hediste diversicolor as the model
      organism. The objective was to study the effects of such leakage in the expected
      scenarios of pH values between 8.0 and 6.0. Polychaetes were exposed for 10 days
      to seawater with sediment samples collected in two different coastal areas, one
      with relatively uncontaminated sediment as reference (RSP) and the other with
      known contaminated sediment (ML), under pre-determined pH conditions. Survival
      and metal accumulation (Al, Fe, Mn, Cu, Zn, As and Hg) in the whole body of H.
      diversicolor were employed as endpoints. Mortality was significant at the lowest
      pH level in the sediment with highest metal concentrations. In general, metal
      concentrations in tissues of individuals exposed to the contaminated sediment
      were influenced by pH. These results indicate that ocean acidification due to CO2
      leakages would provoke increased metal mobilization, causing adverse side effects
      in sediment toxicity.

PMID- 24721119
TI  - Pre-earthquake burden of illness and postearthquake health and preparedness in
      veterans.
AB  - BACKGROUND: During an earthquake, vulnerable populations, especially those with
      chronic conditions, are more susceptible to adverse, event-induced exacerbation
      of chronic conditions such as limited access to food and water, extreme weather
      temperatures, and injury. These circumstances merit special attention when health
      care facilities and organizations prepare for and respond to disasters. METHODS:
      This study explores the relationship between pre-earthquake burden of illness and
      post earthquake health-related and preparedness factors in the US. Data from a
      cohort of male veterans who were receiving care at the Sepulveda Veterans Affairs
      Medical Center (VAMC) in Los Angeles, California USA during the 1994 Northridge
      earthquake were analyzed. RESULTS: Veterans with one or more chronic conditions
      were more likely to report pain lasting two or more days, severe mental/emotional
      stress for more than two weeks, broken/lost medical equipment, having difficulty
      refilling prescriptions, and being unable to get medical help following the quake
      compared to veterans without chronic conditions. In terms of personal emergency
      preparedness, however, there was no association between burden of illness and
      having enough food or water for at least 24 hours after the earthquake.
      CONCLUSION: The relationship that exists between health care providers, including
      both individual providers and organizations like the US Department of Veterans
      Affairs (VA), and their vulnerable, chronically-ill patients affords providers
      the unique opportunity to deliver critical assistance that could make this
      vulnerable population better prepared to meet their post disaster health-related
      needs. This can be accomplished through education about preparedness and the
      provision of easier access to medical supplies. Disaster plans for those who are
      burdened with chronic conditions should meet their social needs in addition to
      their psychological and physical needs.

PMID- 24721120
TI  - Hyperglycemia induces embryopathy, even in the absence of systemic maternal
      diabetes: an in vivo test of the fuel mediated teratogenesis hypothesis.
AB  - Embryonic exposure to excess circulating fuels is proposed to underlie diabetic
      embryopathy. To isolate the effects of hyperglycemia from the many systemic
      anomalies of diabetes, we infused 4 mg/min glucose into the left uterine artery
      of non-diabetic pregnant rats on gestation days (GD) 7-9. Right-sided embryos and
      dams exhibited no glucose elevation. Embryos were assessed on GD13, comparing the
      left versus right uterine horns. Hyperglycemic exposure increased rates of
      embryopathy, resorptions, and worsened embryopathy severity. By contrast, saline
      infusion did not affect any of these parameters. To assess for possible
      embryopathy susceptibility bias between uterine horns, separate dams were given
      retinoic acid (25mg/kg, a mildly embryopathic dose) systemically on GD7.5. The
      resultant embryopathy rates were equivalent between uterine horns. We conclude
      that hyperglycemia, even in the absence of systemic maternal diabetes, is
      sufficient to produce in vivo embryopathy during organogenesis.

PMID- 24721121
TI  - [The strength of fragile].
AB  - Chronic disorder not only modifies the patient's health status; it affects the
      body relationship and its potential; it decreases its power to act, changes its
      relation to time, to its relatives, in shortcut it affects all dimensions of the
      relationship with oneself, with others, and the world. However, if we assume that
      a patient cannot be reduced to his/her illness but must always be treated with
      the respect of a person, we also understand how chronic and debilitating disease
      affects both freedom (or autonomy) and perfectibility (or creativity). By
      analyzing the different forms of freedom of the patient, this paper intends to
      rehabilitate the fragile own strength which is fortitude. It manifests itself in
      attitudes and virtues such as gentleness, patience, attention to the present,
      hope, power of thought. It also intends to show that it is supporting fragile and
      allowing them to develop their own way of acting and living as humanity became
      intelligent and creative. 

PMID- 24721122
TI  - Orthogonal array deciphering MRS medium requirements for isolated Lactobacillus
      rhamnosus ZY with cell properties characterization.
AB  - Lactobacillus rhamnosus is a well-known lactic acid bacterium (LAB), but a new ZY
      strain was isolated for the first time from commercial probiotic powder recently.
      Although many studies have focused on developing cost-effective media for the
      production of LAB, the de Man, Rogosa and Sharpe (MRS) medium is still the most
      common medium for bioprocesses. The aim of the current study is to decipher the
      composition of MRS based on a statistical approach, which will allow a higher
      biomass of Lactobacillus to be obtained. In Taguchi's approach, an L27 orthogonal
      array was adopted to evaluate the significance of 10 ingredients in MRS, in which
      the effects of the components were ranked according to their effect on biomass at
      OD600 as dextrose > MnSO4.H2O > beef extract > CH3COONa > MgSO4 > yeast extract >
      proteose peptone > K2HPO4 > ammonium citrate > Tween 80. Although the individual
      trace elements of ammonium citrate, K2HPO4, CH3COONa and MgSO4 in MRS had an
      insignificant influence on the biomass after statistical analysis, the total
      elimination of trace elements would predominantly affect the cell growth of
      Lactobacillus. Further characterization of the cell properties through attenuated
      total reflectance of Fourier transform infrared (ATR-FTIR) spectroscopy and
      protein identification via SDS-PAGE coupled with tandem mass spectrometry implied
      that dextrose as major carbon source in MRS played the most crucial role for L.
      rhamnosus production.

PMID- 24721123
TI  - Dietary trimethylamine N-oxide exacerbates impaired glucose tolerance in mice fed
      a high fat diet.
AB  - Trimethylamine N-oxide (TMAO) is an oxidation product of trimethylamine (TMA) and
      is present in many aquatic foods. Here, we investigated the effects of TMAO on
      glucose tolerance in high fat diet (HFD)-fed mice. Male C57BL/6 mice were
      randomly assigned to the control, high fat (HF), and TMAO groups. The HF group
      was fed a diet containing 25% fat, and the TMAO group was fed the HFD plus 0.2%
      TMAO for 4 weeks. After 3 weeks of feeding, oral glucose tolerance tests were
      performed. Dietary TMAO increased fasting insulin levels and homeostasis model
      assessment-estimated insulin resistance (HOMA-IR) and exacerbated the impaired
      glucose tolerance in HFD-fed mice. These effects were associated with the
      expression of genes related to the insulin signal pathway, glycogen synthesis,
      gluconeogenesis and glucose transport in liver. mRNA levels of the pro
      inflammatory cytokine MCP-1 increased significantly and of the anti-inflammatory
      cytokine IL-10 greatly decreased in adipose tissue. Our results suggest that
      dietary TMAO exacerbates impaired glucose tolerance, obstructs the hepatic
      insulin signaling pathway, and causes adipose tissue inflammation in mice fed a
      high fat diet. 

PMID- 24721124
TI  - Intraoperative bilateral tension pneumothorax in a patient undergoing breast
      augmentation surgery with general anesthesia.

PMID- 24721125
TI  - To mislead or not to mislead?: letter of response to article: Kokkinos C, Sorkin
      T, Powell B. To Mohs or not to Mohs. J Plast Reconstr Aesthetic Surg (2014) 67:
      23-26.

PMID- 24721126
TI  - Anatomical study of the effects of five surgical maneuvers on palate movement.
AB  - The anatomy of the palate has been extensively described, with a predominant
      focus on palatal musculature. There are no biomechanical studies investigating
      the effects of surgical maneuvers on the palate to aid cleft closure. This study
      aims to describe the soft tissue attachments at different zones and quantify the
      movement following their release. Fourteen adult cadaver heads were dissected.
      The palates were split in the midline and five maneuvers described: Step 1, over
      the hard palate; Step 2, around the greater palatine pedicle; Step 3, over the
      palatine aponeurosis; Step 4, over the hamulus; and Step 5, resulting in a
      hamulus fracture. The movements across the midline at the posterior nasal spine
      following each maneuver were measured. The age range of the 14 heads was between
      60 -75 years. Completion of steps 1 and 2 over the hard palate obtained a mean
      release of 2.6 and 2.0 mm, respectively. The largest movements occurred at Step 3
      (5.7 mm) and Step 4 (3.5 mm), after releasing attachments at the posterior hard
      palate and palatine aponeurosis. Steps 3 and 4 dissections exhibited cumulative
      release, with a maximum movement with Step 3 (p < 0.05). Isolated fracture of the
      hamulus (Step 5) yielded a mean movement of 1.4 mm. Individual steps of
      dissection are described with respect to releasing soft tissue attachments.
      Medial movement of the oral mucosa is quantified with each step of dissection.
      The greatest release occurred with dissection overlying the palatine aponeurosis
      posterior to the hard/soft palate junction. Additional dissection along the
      hamulus (without fracture) added significantly to this release. 

PMID- 24721127
TI  - Remote ischemic preconditioning to reduce contrast-induced nephropathy: study
      protocol for a randomized controlled trial.
AB  - BACKGROUND: Despite the increasing use of pre- and posthydration protocols and
      low-osmolar instead of high-osmolar iodine-containing contrast media, the
      incidence of contrast-induced nephropathy (CIN) is still significant. There is
      evidence that contrast media cause ischemia-reperfusion injury of the medulla.
      Remote ischemic preconditioning (RIPC) is a non-invasive, safe, and low-cost
      method to reduce ischemia-reperfusion injury. METHODS: The RIPCIN study is a
      multicenter, single-blinded, randomized controlled trial in which 76 patients at
      risk of CIN will receive standard hydration combined with RIPC or hydration with
      sham preconditioning. RIPC will be applied by four cycles of 5 min ischemia and 5
      min reperfusion of the forearm by inflating a blood pressure cuff at 50 mmHg
      above the actual systolic pressure. The primary outcome measure will be the
      change in serum creatinine from baseline to 48 to 72 h after contrast
      administration. DISCUSSION: A recent pilot study reported that RIPC reduced the
      incidence of CIN after coronary angioplasty. The unusual high incidence of CIN in
      this study is of concern and limits its generalizability. Therefore, we propose a
      randomized controlled trial to study whether RIPC reduces contrast-induced kidney
      injury in patients at risk for CIN according to the Dutch guidelines. TRIAL
      REGISTRATION: Current Controlled Trials ISRCTN76496973.

PMID- 24721128
TI  - A general approach to mechanism in multiproduct reactions: product-specific
      intermolecular kinetic isotope effects.
AB  - Here we report a general method for the measurement of (13)C kinetic isotope
      effects at natural abundance for reactions that yield two or more products
      concurrently. We use, as an example, a recently reported Co-catalyzed reaction
      between cyclopentene and 1-phenyl-1-propyne. High-precision intermolecular (13)C
      isotope effects are reported for both the formal [2+2] cycloaddition (major) and
      Alder-ene (minor) reaction products. Mechanistic possibilities that are in accord
      with observed isotope effect measurements are discussed. 

PMID- 24721129
TI  - An efficient method for the sanitary vitrification of bovine oocytes in straws.
AB  - BACKGROUND: At present, vitrification has been widely applied to humans, mice and
      farm animals. To improve the efficiency of vitrification in straw, bovine oocytes
      were used to test a new two-step vitrification method in this study. RESULTS:
      When in vitro matured oocytes were exposed to 20% ethylene glycol (EG20) for 5
      min and 40% ethylene glycol (EG40) for 30 s, followed by treatment with 30%
      glycerol (Gly30), Gly40 or Gly50, a volume expansion was observed in Gly30 and
      Gly40 but not Gly50. This indicates that the intracellular osmotic pressure after
      a 30 s differs between EG40 and ranged between Gly40 (approximately 5.6 mol/L)
      and Gly50 (approximately 7.0 mol/L). Since oocytes are in EG40 just for only a
      short period of time (30 s) and at a lower temperature (4 degrees C), we
      hypothesize that the main function of this step in to induce dehydration. Based
      on these results, we omitted the EG40 step, before oocytes were pretreated in
      EG20 for 5 min, exposed to pre-cooled (4 degrees C) Gly50, for 30 s, and then
      dipped into liquid nitrogen. After warming, 81.1% of the oocytes survived, and
      the surviving oocytes developed into cleavage stage embryos (63.5%) or
      blastocysts (20.0%) after parthenogenetic activation. CONCLUSIONS: These results
      demonstrate that in a two-step vitrification procedure, the permeability effect
      in the second step is not necessary. It is possible that the second step is only
      required to provide adequate osmotic pressure to condense the intracellular
      concentration of CPAs to a level required for successful vitrification.

PMID- 24721130
TI  - Inverse association between toenail arsenic and body mass index in a population
      of welders.
AB  - Recent data show that arsenic may play a role in obesity-related diseases.
      However, urinary arsenic studies report an inverse association between arsenic
      level and body mass index (BMI). We explored whether toenail arsenic, a long-term
      exposure measure, was associated with BMI in 74 welders with known arsenic
      exposure. BMI showed significant inverse associations with toenail arsenic
      (p=0.01), which persisted in models adjusted for demographics, diet and work
      history. It is unclear whether low arsenic biomarker concentrations in high BMI
      subjects truly reflect lower exposures, or instead reflect internal or metabolic
      changes that alter arsenic metabolism and tissue deposition. 

PMID- 24721131
TI  - Oxidative stress biomarkers in Eurasian eagle owls (Bubo bubo) in three different
      scenarios of heavy metal exposure.
AB  - The main aim of the present study is the assessment of oxidative stress related
      to metals in the Eurasian eagle owl (Bubo bubo) from three areas (agricultural
      and rural area, industrial area, and mining area) of Murcia, Southern Spain. Mean
      blood metal concentrations were Cd=0.07+/-0.21, Pb=3.27+/-5.21, Cu=10.62+/-4.77,
      Zn=311.47+/-67.14, Hg=2.32+/-3.83 MUg/dl wet weight. Although individuals from
      the mining area had significant higher Pb and Hg concentrations, and significant
      lower glutathione-S-transferase (GST) and catalase (CAT) activities in red blood
      cells (RBC); the lack of differences in oxidative damage to membrane lipids
      (TBARS) among areas suggests that the antioxidant capacity of the different
      populations is able to deal with oxidant species and maintain TBARS levels in the
      same amount. Despite the low levels of metals, several oxidative stress
      biomarkers were correlated with metal concentrations. This study provides
      threshold concentrations at which metals cause effects on the antioxidant system
      in Eagle owls. Blood Cd concentrations greater than 0.3 MUg/dl produced an
      inhibition in GPx (32%) and CAT (26%) activity in RBC. However, Cd concentrations
      higher than 0.02 MUg/dl were enough to produce an inhibition of these enzymes.
      Regarding Pb levels, blood concentrations above 2 MUg/dl produced an inhibition
      of 8% and 10.5% in GPx and CAT activities, respectively, in RBC. A depletion of
      16% and 4% in tGSH levels was associated with Pb concentrations higher than 15
      and 3 MUg/dl, respectively, in individuals from the ancient mine site. In
      addition, Pb concentrations above 2 and 10 MUg/dl produced a TBARS induction of
      10% and 28%, respectively, in individuals from both the industrial and the mining
      area. Finally, Hg concentrations greater than 3 and 10 MUg/dl resulted in a TBARS
      induction of 102% and 190%, respectively, in Eurasian eagle owls from the
      industrial area. Our findings show that Pb may produce effects on oxidative
      stress biomarkers in Strigiformes at lower concentrations than those typically
      accepted for considering physiological effects in Falconiformes (20 ug/dl in
      blood). In addition, we provide new data on Hg and Cd concentrations related to
      effects in the antioxidant system.

PMID- 24721132
TI  - Cashew nut roasting: chemical characterization of particulate matter and
      genotocixity analysis.
AB  - BACKGROUND: Particulate matter (PM) is potentially harmful to health and related
      to genotoxic events, an increase in the number of hospitalizations and mortality
      from respiratory and cardiovascular diseases. The present study conducted the
      first characterization of elemental composition and polycyclic aromatic
      hydrocarbon (PAH) analysis of PM, as well as the biomonitoring of genotoxic
      activity associated to artisanal cashew nut roasting, an important economic and
      social activity worldwide. METHODS: The levels of PM2.5 and black carbon were
      also measured by gravimetric analysis and light reflectance. The elemental
      composition was determined using X-ray fluorescence spectrometry and PAH analysis
      was carried out by gas chromatography-mass spectrometry. Genotoxic activity was
      measured by the Tradescantia pallida micronucleus bioassay (Trad-MCN). Other
      biomarkers of DNA damage, such as nucleoplasmic bridges and nuclear fragments,
      were also quantified. RESULTS: The mean amount of PM2.5 accumulated in the
      filters (January 2124.2 ug/m(3); May 1022.2 ug/m(3); September 1291.9 ug/m(3)),
      black carbon (January 363.6 ug/m(3); May 70 ug/m(3); September 69.4 ug/m(3)) and
      concentrations of Al, Si, P, S, Cl, K, Ca, Ti, Cr, Mn, Fe, Ni, Cu, Zn, Se, Br and
      Pb were significantly higher than the non-exposed area. Biomass burning tracers
      K, Cl, and S were the major inorganic compounds found. Benzo[k]fluoranthene,
      indene[1,2,3-c,d]pyrene, benzo[ghi]perylene, phenanthrene and
      benzo[b]fluoranthene were the most abundant PAHs. Mean benzo[a]pyrene-equivalent
      carcinogenic power values showed a significant cancer risk. The Trad-MCN bioassay
      revealed an increase in micronucleus frequency, 2-7 times higher than the
      negative control and significantly higher in all the months analyzed, possibly
      related to the mutagenic PAHs found. CONCLUSIONS: This study demonstrated that
      artisanal cashew nut roasting is a serious occupational problem, with harmful
      effects on workers' health. Those involved in this activity are exposed to higher
      PM2.5 concentrations and to 12 PAHs considered potentially mutagenic and/or
      carcinogenic. The Trad-MCN with T. pallida was sensitive and efficient in
      evaluating the genotoxicity of the components and other nuclear alterations may
      be used as effective biomarkers of DNA damage.

PMID- 24721133
TI  - Concentrations of the urinary pyrethroid metabolite 3-phenoxybenzoic acid in farm
      worker families in the MICASA study.
AB  - Indoor pesticide exposure is a growing concern, particularly from pyrethroids, a
      commonly used class of pesticides. Pyrethroid concentrations may be especially
      high in homes of immigrant farm worker families who often live in close proximity
      to agricultural fields, and are faced with poor housing conditions, causing
      higher pest infestation and more pesticide use. We investigate exposure of farm
      worker families to pyrethroids in a study of mothers and children living in
      Mendota, CA within the population-based Mexican Immigration to California:
      Agricultural Safety and Acculturation (MICASA) Study. We present pyrethroid
      exposure based on an ELISA analysis of urinary metabolite 3-phenoxybenzoic acid
      (3PBA) levels among 105 women and 103 children. The median urinary 3PBA levels
      (children=2.56 ug/g creatinine, mothers=1.46 ug/g creatinine) were higher than
      those reported in population based studies for the United States general
      population, but similar to or lower than studies with known high levels of
      pyrethroid exposure. A positive association was evident between poor housing
      conditions and the urinary metabolite levels, showing that poor housing
      conditions are a contributing factor to the higher levels of 3PBA seen in the
      urine of these farm worker families. Further research is warranted to fully
      investigate sources of exposure.

PMID- 24721134
TI  - Mercury pollution in fish from South China Sea: levels, species-specific
      accumulation, and possible sources.
AB  - Both total mercury (THg) and methylmercury (MeHg) levels in fish collected from
      South China Sea (SCS) were studied to understand Hg pollution in Chinese tropical
      marine ecosystems. The average THg concentrations in fish species ranged from
      39.6 MUg/kg for rabbitfish (Siganus fuscessens) to 417 MUg/kg for thornfish
      (Terapon jarbua), while those of MeHg varied from 13 MUg/kg (rabbitfish) to 176
      MUg/kg (thornfish). The median values of MeHg/THg ratios in different fish
      species ranged from 36 to 85%. Significant inter-species differences of THg and
      MeHg in fish were observed due to feeding habits and fish sizes. Overall,
      carnivorous fish had higher levels of THg, MeHg and MeHg/THg ratios than
      omnivorous and herbivorous fish. High Hg levels in fish of the SCS were probably
      related to Hg input from atmospheric deposition and anthropogenic activities.

PMID- 24721135
TI  - Reproductive biomarkers responses induced by xenoestrogens in the characid fish
      Astyanax fasciatus inhabiting a South American reservoir: an integrated field and
      laboratory approach.
AB  - Field studies evaluating the effects of endocrine disruption chemicals (EDCs) on
      the fish reproduction are scarce worldwide. The goal of this study was to assess
      hepatic levels of vitellogenin (Vtg), zona radiata proteins (Zrp) and insulin
      like growth factors (IGF-I and IGF-II), and relating them to reproductive
      endpoints in a wild fish population habiting a reservoir that receive domestic
      sewage, agricultural and industrial residues. Adult fish Astyanax fasciatus were
      sampled during the reproductive season in five sites from the Furnas Reservoir,
      Grande River, and Paraguay-Parana basin. As a control to field data, fish were
      experimentally exposed via dietary intake, to oestradiol benzoate (OB) for 7
      days. Fish from site with little anthropogenic interference showed hepatic levels
      of Vtg, Zrp and IGF-I and IGF-II similar to those from the non-treated
      experimental group. In sites located immediately downstream from the municipal
      wastewater discharges, the water total oestrogen was >120 ng/l, and male fish
      displayed increased Vtg and Zrp and decreased IGF-I levels similar to OB treated
      fish. In females, levels of Vtg, Zrp, IGF-I and IGF-II suggest an impairment of
      final oocyte maturation and spawning, as also detected by frequency of over
      ripening, follicular atresia and fecundity. At the sites that receive
      agricultural and industrial residues, the water total oestrogen was <50 ng/l and
      females showed decreased Zrp and increased IGF-II levels associated to reduced
      diameter of vitellogenic follicles, indicating an inhibition of oocyte growth.
      Overall, the current study reports oestrogenic contamination impairing the
      reproduction of a wild fish from a hydroeletric reservoir and, the data
      contribute to improving the current knowledge on relationship between hepatic
      Vtg, Zrp and IGF-I and IGF-II, and reproductive endpoints in a teleost fish. In
      addition, our data point out novel reproductive biomarkers (IGF-I, IGF-II and
      over-ripening) to assessing xenoestrogenic contamination in freshwater
      ecosystems.

PMID- 24721136
TI  - Plasma polychlorinated biphenyl concentrations and immune function in
      postmenopausal women.
AB  - BACKGROUND: Polychlorinated biphenyl (PCB) exposure has been associated with non
      Hodgkin lymphoma in several studies, and the immune system is a potential
      mediator. OBJECTIVES: We analyzed associations of plasma PCBs with immune
      function measures. We hypothesized that higher plasma PCB concentrations are
      associated with lower immune function cross-sectionally, and that increases in
      PCB concentrations over a one year period are associated with decreases in immune
      function. METHODS: Plasma PCB concentrations and immune function [natural killer
      (NK) cell cytotoxicity and PHA-induced T-lymphocyte proliferation (PHA-TLP)] were
      measured at baseline and one year in 109 postmenopausal overweight women
      participating in an exercise intervention study in the Seattle, Washington (USA)
      area. Mixed models, with adjustment for body mass index and other potential
      confounders, were used to estimate associations of PCBs with immune function
      cross-sectionally and longitudinally. RESULTS: Associations of PCBs with immune
      function measures differed across groups of PCBs (e.g., medium- and high
      chlorinated and dioxin-like [mono-ortho-substituted]) and by the time frame for
      the comparison (cross-sectional vs. longitudinal). Higher concentrations of
      medium- and high-chlorinated PCBs were associated with higher PHA-TLP cross
      sectionally but not longitudinally. The mean decrease in 0.5 ug/mL PHA-TLP/50.0
      pmol/g-lipid increase in dioxin-like PCBs over one year was 51.6 (95% confidence
      interval 2.7, 100.5; P=0.039). There was no association between plasma PCBs and
      NK cytotoxicity. CONCLUSIONS: These results do not provide strong evidence of
      impaired cellular immunity from PCB exposure. Larger longitudinal studies with
      greater variability in PCB exposures are needed to further examine temporal
      associations of PCBs with immune function.

PMID- 24721137
TI  - Emergency medical services in India: the present and future.
AB  - India is the second most populous country in the world. Currently, India does not
      have a centralized body which provides guidelines for training and operation of
      Emergency Medical Services (EMS). Emergency Medical Services are fragmented and
      not accessible throughout the country. Most people do not know the number to call
      in case of an emergency; services such as Dial 108/102/1298 Ambulances,
      Centralized Accident and Trauma Service (CATS), and private ambulance models
      exist with wide variability in their dispatch and transport capabilities.
      Variability also exists in EMS education standards with the recent establishment
      of courses like Emergency Medical Technician-Basic/Advanced, Paramedic,
      Prehospital Trauma Technician, Diploma Trauma Technician, and Postgraduate
      Diploma in EMS. This report highlights recommendations that have been put forth
      to help optimize the Indian prehospital emergency care system, including
      regionalization of EMS, better training opportunities, budgetary provisions, and
      improving awareness among the general community. The importance of public and
      private partnerships in implementing an organized prehospital care system in
      India discussed in the report may be a reasonable solution for improved EMS in
      other developing countries.

PMID- 24721138
TI  - Emotional labour and compassionate care: what's the relationship?
AB  - BACKGROUND: Malawi is one of the countries in the Sub-Saharan region of Africa
      severely affected by the HIV pandemic. This being the case, student nurses'
      clinical encounters include caring for patients with HIV and AIDS. OBJECTIVES:
      The study explored the clinical learning experience of undergraduate nursing
      students in Malawi, with the aim of understanding the nature of their experience.
      DESIGN: This was a hermeneutic phenomenological study. SETTING: The study took
      place at a university nursing college in Malawi. PARTICIPANTS: Thirty
      undergraduate nursing students were purposively selected. METHODS: Conversational
      interviews were conducted and a framework developed by modifying Colaizzi's
      procedural steps guided the phenomenological analysis. RESULTS: The participants
      reported their experience during the early years of their studies and their
      current experience at the time of the study, depicting them as novice and senior
      students respectively. The study findings demonstrated an overt fear of
      contracting HIV infection among novice nursing students. Such fear led students
      to deliberately avoid taking care of HIV positive patients and develop a sense of
      legitimate emotional detachment. However, as students progressed in their
      studies, and their knowledge and experiences increased, they realised that HIV
      and AIDS patients needed support and empathy. The learning trajectory demonstrate
      a gradual change from emotional detachment based on fear to a sense of emotional
      engagement built on knowledge, experiential insights and the notion of emotions
      management that led to the provision of care driven by compassion as opposed to
      anxiety. CONCLUSION: The findings illustrate that nursing students need to work
      on their emotions to provide compassionate care. This is consistent with the
      concept of emotional labour and the paper argues that undertaking emotional
      labour is essential in promoting compassionate care.

PMID- 24721139
TI  - Insulin adherence in patients with diabetes: risk factors for injection omission.
AB  - AIMS: The purpose of this study was to evaluate adherence to insulin therapy in
      patients with diabetes. The underlying factors affecting insulin injection
      omission among patients with type 1 or 2 diabetes were also investigated.
      METHODS: This cross-sectional study has been conducted on 507 patients with
      diabetes. Adherence to insulin therapy was measured by the 8-Item Moriskey
      Medication Adherence Scale (MMS) and the autocompliance method. Furthermore,
      socio-demographic, disease and injection-related barriers to insulin injection
      were assessed. RESULTS: Based on the Morisky Green test, 14.3% and 28.8% of
      patients with type 1 and 2 diabetes respectively had low adherence to insulin
      therapy. However, almost all patients were adherent according to the
      autocompliance method. Different factors showed a significant association with
      insulin compliance in both groups. CONCLUSIONS: The current study suggests
      acceptable adherence to insulin therapy among patients with type 1, and poor
      adherence in patients with type 2, diabetes. Our findings regarding barriers with
      significant effect on insulin adherence may be useful to identify patients at
      risk for low compliance, and to guide the design of proper strategies to improve
      adherence and the consequential clinical outcomes.

PMID- 24721140
TI  - Comment on "A primary care based healthy-eating and active living education
      session for weight reduction in the pre-diabetic population" by Daniala et al.

PMID- 24721141
TI  - Effect of beta2 -adrenergic receptor gene Arg16Gly polymorphisms on response to
      long-acting beta2-agonist in Chinese Han asthmatic patients.
AB  - BACKGROUND: To evaluate the effect of variation of the Arg16Gly polymorphism of
      the beta2-adrenergic receptor gene on clinical response to salmeterol
      administered with fluticasone propionate in Chinese Han asthmatic patients.
      METHODS: Moderate persistent asthmatic patients (n = 62) currently receiving
      short-acting beta2-agonists were administered twice-daily therapy with
      salmeterol/fluticasone propionate 50/250 MUg in a single inhaler for 12 weeks,
      followed by a 2-to-4-day run-out period. Using direct DNA sequencing, five single
      nucleotide polymorphisms (SNPs) in the promoter and coding block regions of beta2
      adrenergic receptor gene were determined in 62 subjects and haplotypes were
      combined. RESULTS: There was sustained and significant improvement (p < 0.001)
      over baseline in all measures of asthma control in subjects receiving salmeterol
      and fluticasone, regardless of Arg16Gly genotype. However, there was no
      significant difference in the improvement among three genotypes (p > 0.05).
      Responses to salmeterol did not appear to be modified by haplotype pairs (p >
      0.05). During the run-out period, all subjects had similar decreases in measures
      of asthma control, with no differences between genotypes (p > 0.05). CONCLUSIONS:
      Response to salmeterol does not vary with Arg16Gly polymorphisms after chronic
      dosing with inhaled corticosteroids in Chinese Han asthmatic patients.

PMID- 24721142
TI  - Identification of two SNPs in myostatin (MSTN) gene of Takifugu rubripes and
      their association with growth traits.
AB  - The myostatin (MSTN) is a member of transforming growth factor-beta superfamily
      which inhibits muscle growth. In this study, the genomic DNA sequence of MSTN
      gene was cloned from Takifugu rubripes (T. rubripes). Two polymorphisms of the
      MSTN gene were detected by polymerase chain reaction-single strand conformation
      polymorphism (PCR-SSCP) and DNA sequencing methods in 296 T. rubripes. One A748G
      locates in exon 2 and the other, C1197T, in intron 2. Analysis showed that the
      A748G mutation caused an amino acid change from Thr to Ala (Ala166Glu). These two
      SNPs showed a low degree of linkage disequilibrium and four haplotypes were
      identified. The most frequent haplotype was AC, which occurred at a frequency of
      44.3%. Association analyses between these two SNPs and growth traits showed that
      the individuals with genotype CT and TT of the mutation C1197T had significantly
      higher body mass, body length and body height than those with genotype CC (P <
      0.05). These results show that MSTN gene can be utilized as a candidate gene for
      molecular marker-assisted breeding of T. rubripes.

PMID- 24721144
TI  - Medical and psychosocial needs of Olympic and Pan American athletes after the
      2010 earthquake in Haiti: an opportunity to promote resilience through sports
      medicine and public diplomacy.
AB  - INTRODUCTION: On January 12, 2010, a magnitude 7.0 earthquake devastated Haiti.
      Data regarding the prevalence of medical and psychosocial needs after the
      earthquake is scarce, complicating informed targeting of aid. The effects of the
      earthquake on athletes, as they differ from the general population, are
      especially unclear. The Center for Disaster Resilience (Boston, Massachusetts
      USA) and the Disaster Medicine Section at Harvard Medical School (Boston,
      Massachusetts USA) have partnered with Child in Hand to care for athletes
      training for the Pan American and Olympic games in Haiti, as well as for children
      from the general population. This report presents preliminary epidemiologic data
      illustrating the burden of medical and psychosocial needs of Haitian athletes and
      the general population after the earthquake of 2010. METHODS: The study was a
      cross-sectional, comparative study conducted a year after the earthquake. The
      study group comprised 104 athletes, aged 12-18 years, enrolled from the National
      Sports Center in Haiti. The control group (N = 104) from the general population
      was age- and gender-matched from orphanages and schools in and around Port-au
      Prince, Haiti. Medical teams assessed illness based on history and physicals.
      Psychosocial teams utilized the Child Psychosocial Distress Screener (CPDS). Two
      proportion z tests and two-sample t tests were used to compare the proportions of
      medical illnesses, mean CPDS scores, and proportion of CPDS scores indicating
      treatment. RESULTS: The most prevalent medical condition in athletes was
      musculoskeletal pain, which was more common than in controls (49% versus 2.9%).
      All other medical conditions were more common in the controls than athletes:
      abdominal pain (28.8% versus 4.8%); headache (22.1% versus 5.8%); fever (15.4%
      versus 1%); and malnutrition (18.3% versus 1.9%). In contrast, there was no
      significant difference in mean psychosocial scores and the proportion of scores
      indicating treatment between athletes and controls. CONCLUSION: Elite athletes in
      Haiti have a low prevalence of most medical conditions after the disaster,
      suggesting that they may be protected from risk factors affecting the general
      population. However, athletes have a higher prevalence of musculoskeletal
      ailments and were not protected from psychosocial distress. This presents an
      opportunity for sports medicine physicians and mental health providers to engage
      in efforts to rebuild Haiti on an individual level by providing targeted care to
      athletes, and on a larger scale, by supporting international sports competition,
      which enhances human capital and facilitates public diplomacy.

PMID- 24721143
TI  - Combining motivational and volitional strategies to promote unsupervised walking
      in patients with fibromyalgia: study protocol for a randomized controlled trial.
AB  - BACKGROUND: Fibromyalgia patients are often advised to engage in regular low- to
      moderate-intensity physical exercise. The need of fibromyalgia patients to walk
      has been stressed in previous research. Behavioral self-regulation theories
      suggest that a combination of motivational aspects (to develop or strengthen a
      behavioral intention: Theory of Planned Behavior) and volitional aspects
      (engagement of intention in behavior: implementation intentions) is more
      effective than a single intervention. In this paper, we describe a protocol for
      identifying the motivational processes (using the Theory of Planned Behavior)
      involved in the practice of walking (phase I) and for studying the efficacy of an
      intervention that combines motivational and volitional contents to enhance the
      acquisition and continuation of this exercise behavior (phase II). The paper also
      shows the characteristics of eligible individuals (women who do not walk) and
      ineligible populations (women who walk or do not walk because of comorbidity
      without medical recommendation to walk). Both groups consist of members of any of
      four patients' associations in Spain who are between 18 and 70 years of age and
      meet the London Fibromyalgia Epidemiology Study Screening Questionnaire criteria
      for fibromyalgia. Furthermore, using this study protocol, we will explore the
      characteristics of participants (eligible women who agreed to participate in the
      study) and nonparticipants (eligible women who refused to participate).
      METHODS/DESIGN: Two studies will be conducted: Phase I will be a cross-sectional
      study, and phase II will be a triple-blind, randomized longitudinal study with
      two treatment groups and one active control group. The questionnaires were sent
      to a total of 2,227 members of four patients' associations in Spain. A total of
      920 participants with fibromyalgia returned the questionnaires, and 582 were
      ultimately selected to participate. DISCUSSION: The first data gathered have
      allowed us to identify the characteristics of the study population and they
      support the appropriateness of the inclusion criteria.. When the study is
      complete, the results will enable us to establish whether this kind of
      intervention can be used as a self-regulation tool for increasing and maintaining
      walking as unsupervised physical exercise of low to moderate intensity in
      fibromyalgia patients. TRIAL REGISTRATION:  TRIAL REGISTRATION NUMBER:
      ISRCTN68584893.

PMID- 24721145
TI  - Association of n-3 polyunsaturated fatty acids and inflammatory indicators with
      renal function decline in type 2 diabetes.
AB  - BACKGROUND & AIMS: The n-3 polyunsaturated fatty acids (PUFAs) and the
      inflammatory indicator, interleukin-6 (IL-6), have been implied in the
      development of renal dysfunction. This longitudinal study examined the effect of
      n-3 PUFAs and IL-6 on the risk of renal function decline and explored whether n-3
      PUFAs modify the effect of inflammatory indicators on renal dysfunction risk in
      type 2 diabetes. METHODS: Studying 676 type 2 diabetic patients, we analyzed
      erythrocyte fatty acids and inflammatory markers in 2008 and estimated glomerular
      filtration rate (eGFR) in 2008 and 2012. Renal function decline was defined as an
      eGFR decline of >=25% over a 4-year period. RESULTS: Multivariable logistic
      regression revealed erythrocyte total PUFAs, n-3 PUFAs, and n-3/n-6 PUFA ratio
      correlated negatively with risk of renal function decline (OR = 0.75, 0.78, and
      0.61, respectively, all p < 0.01), while n-6 PUFAs did not. IL-6 independently
      predicted risk of renal dysfunction (OR = 1.18, p = 0.015). Stratifying
      erythrocyte PUFAs into low (<50(th) percentile) or high group (>=50(th)
      percentile), we found a positive association between IL-6 and risk of renal
      dysfunction only in the low n-3 PUFA (OR = 1.27, p = 0.035), low n-3/n-6 PUFA (OR
      = 1.27, p = 0.034), and low total PUFA groups (OR = 1.36, p = 0.005), but not in
      the high groups. CONCLUSIONS: High PUFA concentrations, especially n-3 or higher
      n-3/n-6 PUFA ratio, may exert protective effects against renal function
      impairment in type 2 diabetic patients. Whether the effect is mediated via
      modification of inflammatory biomarker such as IL-6 by high n-3 PUFA status
      warrants further investigation.

PMID- 24721146
TI  - A systematic review of methods to predict maximal oxygen uptake from submaximal,
      open circuit spirometry in healthy adults.
AB  - OBJECTIVES: This systematic review aimed to (i) report the accuracy of submaximal
      exercise-based predictive equations that incorporate oxygen uptake (measured via
      open circuit spirometry) to predict maximal oxygen uptake (VO2max) and (ii)
      provide a critical reflection of the data to inform health professionals and
      researchers when selecting a prediction equation. DESIGN: Systematic review.
      METHODS: A systematic search of MEDLINE, EMBASE (via OvidSP), CINAHL, SPORTDiscus
      (via EBSCO Host) and Scopus databases was undertaken in February 2013. Studies
      were required to report data on healthy participants aged 18-65y. Following
      tabulation of extracted data, a narrative synthesis was conducted. RESULTS: From
      a total of 7597 articles screened, 19 studies were included, from which a total
      of 43 prediction equations were extracted. No significant difference was reported
      between the measured and predicted VO2max in 28 equations. Pearson's correlation
      coefficient between the predicted and measured VO2max ranged from r=0.92 to
      r=0.57. The variables most commonly used in predictive equations were heart rate
      (n=19) and rating of perceived exertion (n=24). CONCLUSIONS: Overall, submaximal
      exercise-based equations using open circuit spirometry to predict VO2max are
      moderately to highly accurate. The heart rate and rating of perceived exertion
      methods of predicting VO2max were of similar accuracy. Important factors to
      consider when selecting a predictive equation include: the level of exertion
      required; participant medical conditions or medications; the validation
      population; mode of ergometry; time and resources available for familiarisation
      trials; and the level of bias of the study from which equations are derived.

PMID- 24721147
TI  - [The arteriovenous fistula is an additional risk factor for developing carpal
      tunnel syndrome in hemodialysis patients].
AB  - INTRODUCTION: Carpal tunnel syndrome (CTS) is the most frequent entrapment
      neuropathy reported in patients with renal failure undergoing periodic
      haemodialysis. The role of arteriovenous fistula was discussed. The aim of this
      study was to investigate this relationship. METHODS: Subjects for this study were
      hemodialysis patients who underwent systematic electroneuromyography between
      January 2003 and December 2010. Only patients with unilateral fistulae were
      included for the study. RESULTS: One hundred and thirty-four out of 155 patients
      were examined. CTS was noted in 106 patients and was detectable only in ENMG in
      42% of cases. It was more frequent (P<0.001) and more severe in the side of
      fistulae (P=0.08). Besides, development of CTS was only correlated with the
      longer duration of dialysis (P=0.005). This duration was significantly shorter in
      patients with CTS and diabetes. CONCLUSION: The positive correlation between CTS
      and aretriovenous fistulae confirms the pathogenic role of this latter. The risk
      rises in these patients with the duration of hemodialysis and the presence of
      diabetes.

PMID- 24721148
TI  - Optimization of electron microscopy for human brains with long-term fixation and
      fixed-frozen sections.
AB  - BACKGROUND: Abnormal connectivity across brain regions underlies many
      neurological disorders including multiple sclerosis, schizophrenia and autism,
      possibly due to atypical axonal organization within white matter. Attempts at
      investigating axonal organization on post-mortem human brains have been hindered
      by the availability of high-quality, morphologically preserved tissue,
      particularly for neurodevelopmental disorders such as autism. Brains are
      generally stored in a fixative for long periods of time (often greater than 10
      years) and in many cases, already frozen and sectioned on a microtome for
      histology and immunohistochemistry. Here we present a method to assess the
      quality and quantity of axons from long-term fixed and frozen-sectioned human
      brain samples to demonstrate their use for electron microscopy (EM) measures of
      axonal ultrastructure. RESULTS: Six samples were collected from white matter
      below the superior temporal cortex of three typically developing human brains and
      prepared for EM analyses. Five samples were stored in fixative for over 10 years,
      two of which were also flash frozen and sectioned on a freezing microtome, and
      one additional case was fixed for 3 years and sectioned on a freezing microtome.
      In all six samples, ultrastructural qualitative and quantitative analyses
      demonstrate that myelinated axons can be identified and counted on the EM images.
      Although axon density differed between brains, axonal ultrastructure and density
      was well preserved and did not differ within cases for fixed and frozen tissue.
      There was no significant difference between cases in axon myelin sheath thickness
      (g-ratio) or axon diameter; approximately 70% of axons were in the small (0.25
      MUm) to medium (0.75 MUm) range. Axon diameter and g-ratio were positively
      correlated, indicating that larger axons may have thinner myelin sheaths.
      CONCLUSION: The current study demonstrates that long term formalin fixed and
      frozen-sectioned human brain tissue can be used for ultrastructural analyses.
      Axon integrity is well preserved and can be quantified using the methods
      presented here. The ability to carry out EM on frozen sections allows for
      investigation of axonal organization in conjunction with other cellular and
      histological methods, such as immunohistochemistry and stereology, within the
      same brain and even within the same frozen cut section.

PMID- 24721149
TI  - Trends in ages at key reproductive transitions in the United States, 1951-2010.
AB  - BACKGROUND: Key sexual and reproductive health milestones typically mark changing
      life stages with different fertility intentions and family planning needs.
      Knowing the typical ages at such events contributes to our understanding of
      changes in family formation and transition to adulthood and helps inform needs
      for reproductive health services. METHODS: We used data from the 1982-2010
      National Surveys of Family Growth and the 1995 National Survey of Adolescent
      Males and event history methods to examine trends over time for women and men in
      the median ages at several reproductive and demographic events. FINDINGS: Women's
      reports indicate that age at menarche has changed little since 1951. Women's and
      men's median ages at first sex declined through the 1978 birth cohort, but
      increased slightly since then, to 17.8 years for women and 18.1 for men. The
      interval from first sex to first contraceptive use has narrowed, although
      Hispanic women have a longer interval. Age at first union (defined as the earlier
      of first marriage or first cohabiting relationship) has remained relatively
      stable, but the time between median age at first sex and median age at first
      birth has increased to 9.2 years for women and 11.4 for men. For some women and
      men born in the late 1970s, median age at first birth was earlier than median age
      at first marriage for the first time in at least the past several decades.
      CONCLUSION: The large majority of the reproductive years are spent sexually
      active. Thus, women have a lengthy period during which they require effective
      methods. In particular, the period between first sex and first childbearing has
      lengthened, but long-acting method use, although increasing, has not kept up with
      this shift. Moving the contraceptive method mix toward underutilized but highly
      effective contraceptive methods has the potential to reduce the unintended
      pregnancy rate.

PMID- 24721150
TI  - Why do a wide variety of animals retain multiple isoforms of cyclooxygenase?
AB  - Cyclooxygenase (COX) has been cloned from the phyla Cnidaria, Mollusca,
      Arthropoda, and Chordata of the animal kingdom. Many organisms have multiple COX
      isoforms that have arisen from gene duplication. It is not well understood why
      there are multiple COX isoforms in the same organism, or when duplication of the
      COX gene occurred. Here, we summarize the current knowledge of the evolutionary
      history of COX in the animal kingdom and discuss the reasons why the multiple COX
      system has been retained so widely. The phylogenetic analysis suggests that all
      COX genes in animals may descend from a common ancestor and that the duplication
      of an ancestral COX gene might occur within each lineage after the divergence of
      the animal. In most instances, the expressions of multiple COX isoforms are
      separately regulated and these isoforms play different and important
      pathophysiological roles in each organism. This may be the reason why multiple
      COX isoforms are widely retained. 

PMID- 24721151
TI  - Nitrite treatment rescues cardiac dysfunction in aged mice treated with
      conjugated linoleic acid.
AB  - Conjugated linoleic acid (cLA) is a commercially available weight-loss supplement
      that is not currently regulated by the U.S. FDA. Numerous studies suggest that
      cLA mediates protection against diseases including cancer, diabetes,
      atherosclerosis, immune function, and obesity. Based upon these reports, it was
      hypothesized that supplementation with cLA would improve heart function in aged
      wild-type (WT) mice. At 10 months of age, mice were treated with cLA, nitrite, or
      the combination of the two. Echocardiograms revealed that cardiac function was
      decreased in aged compared to young WT mice, as determined by percentage of
      fractional shortening. Also, contrary to the hypothesis, mice that received cLA
      (6-week treatment) had significantly worse cardiac function compared to controls.
      This effect was attenuated when mice were cotreated with cLA and nitrite. Taken
      together, these results suggest that cLA-mediated cardiac injury can be
      circumvented by nitrite supplementation in a murine model of aging. 

PMID- 24721152
TI  - Rhein exerts pro- and anti-inflammatory actions by targeting IKKbeta inhibition
      in LPS-activated macrophages.
AB  - Because steroids and cyclooxygenase inhibitors may cause serious side effects,
      the IkappaB kinase (IKK) beta/nuclear factor-kappaB (NF-kappaB) system has become
      an intriguing candidate anti-inflammatory target. Rhein, the active metabolite of
      diacerein, possesses anti-inflammatory ability with a gastrointestinal protective
      effect. However, in a preliminary study, we accidentally found that rhein showed
      both anti- and proinflammatory activities in lipopolysaccharide (LPS)-activated
      macrophages. Thus, in this study, we explored the underlying molecular mechanisms
      of the dual effects of rhein. In LPS-activated macrophages, rhein inhibits NF
      kappaB activation and sequentially suppresses its downstream inducible nitric
      oxide synthase, interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha),
      and interleukin-1beta (IL-1beta) transcription and supernatant nitric oxide and
      IL-6 levels by inhibiting IKKbeta (IC50 ~ 11.79MUM). But in the meantime, rhein
      enhances the activity of caspase-1 by inhibiting intracellular (in situ) IKKbeta,
      in turn increasing the IL-1beta and high-mobility-group box 1 release, which can
      be amplified by rhein's reductive effect on intracellular superoxide anion.
      Unexpectedly, it is because of IKKbeta inhibition that rhein significantly
      enhances TNF-alpha secretion and phagocytosis in macrophages with or without LPS.
      These results indicate that rhein exerts anti- and proinflammatory activities by
      targeting IKKbeta inhibition, providing a molecular mechanism for the
      unanticipated role of rhein in macrophages. Furthermore, our study also
      highlights the potential complications of IKKbeta inhibitor (e.g., rhein,
      diacerein, etc.) application in inflammation disorders, for the overall effects
      of IKKbeta inhibition in various organ systems and disease processes are not
      easily predictable under all circumstances. 

PMID- 24721153
TI  - Nonallergenic urushiol derivatives inhibit the oxidation of unilamellar vesicles
      and of rat plasma induced by various radical generators.
AB  - Urushiols consist of an o-dihydroxybenzene (catechol) structure and an alkyl
      chain of 15 or 17 carbons in the 3-position of a benzene ring and are allergens
      found in the family Anacardiaceae. We synthesized various veratrole (1,2
      dimethoxybenzene)-type and catechol-type urushiol derivatives that contained
      alkyl chains of various carbon atom lengths, including -H, -C1H3, -C5H11, 
      C10H21, -C15H31, and -C20H41, and investigated their contact hypersensitivities
      and antioxidative activities. 3-Decylcatechol and 3-pentadecylcatechol displayed
      contact hypersensitivity, but the other compounds did not induce an allergic
      reaction, when the ears of rats were sensitized by treatment with the compounds
      every day for 20 days. Catechol-type urushiol derivatives (CTUDs) exerted very
      high radical-scavenging activity on the 1,1-diphenyl-2-picrylhydrazyl radical and
      inhibited lipid peroxidation in a methyl linoleate solution induced by 2,2'
      azobis(2,4-dimethylvaleronitrile) (AMVN). However, veratrole-type urushiol
      derivatives did not scavenge or inhibit lipid peroxidation. CTUDs also acted as
      effective inhibitors of lipid peroxidation of the egg yolk phosphatidylcholine
      large unilamellar vesicle (PC LUV) liposome system induced by various radical
      generators such as AMVN, 2,2'-azobis(2-amidino-propane) dihydrochloride, and
      copper ions, although their efficiencies differed slightly. In addition, CTUDs
      suppressed formation of cholesteryl ester hydroperoxides in rat blood plasma
      induced with copper ions. CTUDs containing more than five carbon atoms in the
      alkyl chain showed excellent lipophilicity in a n-octanol/water partition
      experiment. These compounds also exhibited high affinities to the liposome
      membrane using the ultrafiltration method of the PC LUV liposome system.
      Therefore, CTUDs seem to act as efficient antioxidative compounds against
      membranous lipid peroxidation owing to their localization in the phospholipid
      bilayer. These results suggest that nonallergenic CTUDs act as antioxidants to
      protect against oxidative damage of cellular and subcellular membranes. 

PMID- 24721154
TI  - Rapid determination of leaf area and plant height by using light curtain arrays
      in four species with contrasting shoot architecture.
AB  - BACKGROUND: Light curtain arrays (LC), a recently introduced phenotyping method,
      yield a binary data matrix from which a shoot silhouette is reconstructed. We
      addressed the accuracy and applicability of LC in assessing leaf area and maximum
      height (base to the highest leaf tip) in a phenotyping platform. LC were
      integrated to an automated routine for positioning, allowing in situ
      measurements. Two dicotyledonous (rapeseed, tomato) and two monocotyledonous
      (maize, barley) species with contrasting shoot architecture were investigated. To
      evaluate if averaging multiple view angles helps in resolving self-overlaps, we
      acquired a data set by rotating plants every 10 degrees  for 170 degrees . To
      test how rapid these measurements can be without loss of information, we
      evaluated nine scanning speeds. Leaf area of overlapping plants was also
      estimated to assess the possibility to scale this method for plant stands.
      RESULTS: The relation between measured and calculated maximum height was linear
      and nearly the same for all species. Linear relations were also found between
      plant leaf area and calculated pixel area. However, the regression slope was
      different between monocotyledonous and dicotyledonous species. Increasing the
      scanning speed stepwise from 0.9 to 23.4 m s-1 did not affect the estimation of
      maximum height. Instead, the calculated pixel area was inversely proportional to
      scanning speed. The estimation of plant leaf area by means of calculated pixel
      area became more accurate by averaging consecutive silhouettes and/or increasing
      the angle between them. Simulations showed that decreasing plant distance
      gradually from 20 to 0 cm, led to underestimation of plant leaf area owing to
      overlaps. This underestimation was more important for large plants of
      dicotyledonous species and for small plants of monocotyledonous ones.
      CONCLUSIONS: LC offer an accurate estimation of plant leaf area and maximum
      height, while the number of consecutive silhouettes that needs to be averaged is
      species-dependent. A constant scanning speed is important for leaf area
      estimations by using LC. Simulations of the effect of varying plant spacing gave
      promising results for method application in sets of partly overlapping plants,
      which applies also to field conditions during and after canopy closure for crops
      sown in rows.

PMID- 24721155
TI  - Effects of carbon tetrachloride on oxidative stress, inflammatory response and
      hepatocyte apoptosis in common carp (Cyprinus carpio).
AB  - In the present study, the cellular and molecular mechanism of carbon
      tetrachloride (CCl4)-induced hepatotoxicity in fish was investigated by studying
      the effects of CCl4 on the oxidative stress, inflammatory response and hepatocyte
      apoptosis. Common carp were given an intraperitoneal injection of 30% CCl4 in
      arachis oil (0.5ml/kg body weight). At 72h post-injection, blood were collected
      to measure glutamate pyruvate transaminase (GPT), glutamate oxalate transaminase
      (GOT), superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT),
      glutathione (GSH), total antioxidant capacity (T-AOC) and malondialdehyde (MDA),
      liver samples were taken to analyze toll-like receptor 4 (TLR4), cytochrome P450
      2E1 (CYP2E1) and gene expressions of inflammatory cytokines and nuclear factor
      kappaB (NF-kappaB/cREL). Cell viability and apoptosis were analyzed after
      treatment of the primary hepatocytes with CCl4 at 8mM. The results showed that
      CCl4 significantly increased the levels of GPT, GOT, MDA, TLR4 and CYP2E1,
      reduced the levels of SOD, GPx, CAT, GSH and T-AOC, and up-regulated the gene
      expressions of NF-kappaB/cREL and inflammatory cytokines including tumor necrosis
      factor-alpha (TNF-alpha), inducible nitric oxide synthase (iNOS), IL-1beta, IL-6
      and IL-12. In vitro, CCl4 caused a dramatic loss in cell viability and induced
      hepatocyte apoptosis. Overall results suggest that oxidative stress lipid
      peroxidation, and TNF-alpha/NF-kappaB and TRL4/NF-kappaB signaling pathways play
      important roles in CCl4-induced hepatotoxicity in fish. 

PMID- 24721156
TI  - In ovo exposure to selenomethionine via maternal transfer increases developmental
      toxicities and impairs swim performance in F1 generation zebrafish (Danio rerio).
AB  - Selenomethionine (SeMet) is the major form of organoselenium present in food.
      Adult female fish can accumulate greater concentrations of SeMet from food in
      aquatic ecosystems contaminated with selenium (Se), and maternal transfer to eggs
      increases the incidence of developmental toxicities and mortality in F1
      generation larval fish. The present study was designed to investigate both
      immediate and persistent adverse effects of graded exposure to SeMet via in ovo
      maternal transfer to F1 generation zebrafish (Danio rerio). Adult zebrafish were
      fed either control food (1.3MUg Se/g, dry mass or d.m.) or food spiked with
      increasing concentrations of Se (3.7, 9.6 or 26.6MUg Se/g, d.m.) in the form of
      SeMet for 60d at 5% body mass/d ration, and an additional 30-40d with equal
      rations (2.5%) of control or SeMet-spiked diets and clean chironomids.
      Concentrations of Se in eggs of adult zebrafish fed 1.3, 3.7, 9.6 or 26.6MUg Se/g
      d.m. were 2.1, 6.0, 9.6 and 21.9MUg Se/g d.m., respectively. Exposure to SeMet
      via in ovo maternal transfer increased larval zebrafish mortalities in a
      concentration- and time-dependent fashion. In order to investigate persistent
      adverse effects of in ovo exposure to excess Se, we determined swim performance
      (Ucrit), tailbeat amplitude and frequency, energy stores (whole body
      triglycerides and glycogen), and a marker of the physiological stress response
      (whole body cortisol) of F1 generation zebrafish at 140 days post-fertilization
      (dpf), and reproductive performance at 180dpf. Reduced Ucrit was observed in F1
      generation adult zebrafish exposed to >=6.0MUg Se/g d.m. Concentrations of whole
      body glycogen in the 6.0MUg Se/g d.m. exposed group were significantly lower than
      the controls. However, no differences were found in concentrations of whole body
      triglycerides or cortisol in adult zebrafish. Mortalities and developmental
      toxicities in offspring (F2 generation) of F1 generation adult zebrafish exposed
      to excess Se via in ovo maternal transfer were comparable to the controls.
      Overall, the results of this study suggest that exposure to greater
      concentrations of SeMet via in ovo maternal transfer can significantly impact the
      survivability of F1 generation fish, which could impact recruitment of wild fish
      inhabiting Se-contaminated aquatic ecosystems. 

PMID- 24721157
TI  - Current practice in the diagnosis and management of IBD-associated anaemia and
      iron deficiency in Germany: the German AnaemIBD Study.
AB  - BACKGROUND/AIM: Anaemia is a common complication in inflammatory bowel disease
      (IBD), frequently resulting from iron deficiency. IBD guidelines advocate
      intravenous iron administration although some patients respond to oral
      supplementation. This non-interventional study investigates the current status of
      anaemia management in German IBD patients. METHODS: Baseline data on pre-study
      treatment for anaemia were retrospectively analysed in IBD patients with anaemia
      participating in a prospective trial of the efficacy and safety of ferric
      carboxymaltose. Data were collected from 55 German gastroenterological centres up
      to August 2010. Subjects had received care at their centre for at least 12 months
      prior to baseline. RESULTS: 193 cases of IBD-associated anaemia (115 Crohn's
      disease, 77 ulcerative colitis) were analysed (mean age: 39 years (18-83), 79
      (41%) males). Anaemia and iron status were usually assessed by haemoglobin
      (100%), serum ferritin (97%), and transferrin saturation (82%). In the previous 6
      months, only 84 patients (43.5%) had been treated for anaemia: 47 (56%) with oral
      iron, 13 (15%) parenteral iron, 16 (19%) oral plus parenteral iron and 8 (10%)
      transfusions. No patients received erythropoietin stimulating agents. CONCLUSION:
      Although intravenous iron supplementation is recommended in IBD patients, current
      German practice still relies on oral therapy, even in severe anaemia. The high
      incidence of severe anaemia in this cohort reflects inadequate iron replacement
      and status monitoring. While the proportion of IBD patients with inadequately
      treated anaemia/iron deficiency is unknown, greater awareness of existing
      guidelines for iron deficiency management in IBD patients appears necessary.

PMID- 24721158
TI  - Predicting coronary heart disease in remote settings: a prospective, cross
      sectional observational study.
AB  - BACKGROUND: Coronary heart disease (CHD) places a major burden on the Australian
      health care system. Determining the likelihood of CHD in a patient presenting
      with chest pain can be particularly difficult in a remote setting where access to
      transportation and specialised investigations including myocardial stress studies
      and coronary angiography can be difficult and delayed. The objective is to
      develop a predictive model for determining the risk of CHD, including the value
      of high sensitivity C-reactive protein (hsCRP), in patients presenting with chest
      pain with a particular emphasis on resources and information likely to be
      available in a remote primary health care setting. METHODS: A prospective, cross
      sectional observational study of patients with no prior diagnosis of CHD
      presenting to a specialist chest pain assessment clinic at Cairns Hospital from
      November 2012 to May 2013. RESULTS: Out of the 163 participants included in the
      study analyses, a total of 38 were classified as CHD likely (23.3% (95% CI 17.1
      30.6)). Logistic regression modelling identified two factors that were
      independently associated with likely CHD, namely the presence of typical chest
      pain (OR 83.7 (95% CI 21.7-322.1)) and an abnormal baseline ECG (OR 12.8 (95% CI
      1.9-86.0)). CONCLUSION: In this study, it was demonstrated that the presence of
      typical chest pain and an abnormal resting ECG, remain the cornerstone of
      predicting a subsequent diagnosis of CHD. This information is easily accessible
      in remote primary health care and should be utilised to expedite assessment in
      patients presenting with symptoms suggestive of CHD.

PMID- 24721159
TI  - The prevalence and trends in overweight and obesity in Irish adults between 1990
      and 2011.
AB  - OBJECTIVE: Obesity is a serious public health issue, the prevalence of which is
      increasing globally. The present study aimed to investigate trends in overweight
      and obesity in Irish adults between 1990 and 2011. DESIGN: Anthropometric data
      from three Irish national food consumption surveys were used to calculate trends
      in BMI, waist circumference and waist:hip ratio. SETTING: Three cross-sectional
      food consumption surveys: the Irish National Nutrition Survey (1990), the
      North/South Ireland Food Consumption Survey (2001) and the National Adult
      Nutrition Survey (2011). SUBJECTS: A collective sample of free-living Irish
      adults (n 3125), aged 18-64 years. RESULTS: There were significant increases in
      mean weight, height and BMI from 1990 to 2011. Significant increments were also
      reported in waist and hip circumferences and waist:hip ratio between 2001 and
      2011, with concurrent increases in the proportion of individuals at risk of
      developing CVD, particularly females aged 18-35 years. In 2011, 23.4 % of the
      Irish population was classified as obese; with the mean BMI increasing by 1.1
      kg/m2 between 1990 and 2001 and by 0.6 kg/m2 between 2001 and 2011. CONCLUSIONS:
      The present paper characterises obesity levels in Irish adults from 1990 to 2011.
      Absolute levels of overweight and obesity have increased between these time
      points. Of concern is the increase in the proportion of young women classified as
      at risk of CVD, using waist circumference and waist:hip ratio. Effective
      prevention strategies are needed to avoid further increases.

PMID- 24721160
TI  - Subclinical inflammation on MRI of hand and foot of anticitrullinated peptide
      antibody-negative arthralgia patients at risk for rheumatoid arthritis.
AB  - INTRODUCTION: It is known that anticitrullinated peptide antibody (ACPA)-positive
      rheumatoid arthritis (RA) has a preclinical phase. Whether this phase is also
      present in ACPA-negative RA is unknown. To determine this, we studied ACPA
      negative arthralgia patients who were considered prone to progress to RA for
      local subclinical inflammation observed on hand and foot magnetic resonance
      imaging (MRI) scans. METHODS: We studied a total of 64 ACPA-negative patients
      without clinically detectable arthritis and with arthralgia of the small joints
      within the previous 1 year. Because of the character of the patients' symptoms,
      the rheumatologists considered these patients to be prone to progress to RA. For
      comparisons, we evaluated 19 healthy, symptom-free controls and 20 ACPA-negative
      RA patients, who were identified according to the 1987 American Rheumatism
      Association criteria. All participants underwent MRI of unilateral wrist,
      metacarpophalangeal and metatarsophalangeal joints. Synovitis and bone marrow
      oedema (BME) were scored according to the OMERACT rheumatoid arthritis magnetic
      resonance imaging scoring system, and the scores were summed to yield the 'MRI
      inflammation score'. Scores were compared between groups. Among the ACPA-negative
      arthralgia patients, MRI inflammation scores were related to C-reactive protein
      (CRP) levels and the tenderness of scanned joints. RESULTS: MRI inflammation
      scores increased progressively among the groups of controls and ACPA-negative
      arthralgia and RA patients (median scores = 0, 1 and 10, respectively; P <
      0.001). The MRI inflammation scores of ACPA-negative arthralgia patients were
      significantly higher than those of controls (P = 0.018). In particular, the
      synovitis scores were higher in ACPA-negative arthralgia patients (P = 0.046).
      Among the ACPA-negative arthralgia patients, inflammation was observed
      predominantly in the wrist (53%). The synovitis scores were associated with CRP
      levels (P = 0.007) and joint tenderness (P = 0.026). Despite the limited follow
      up duration, five patients developed clinically detectable arthritis. These five
      patients had higher scores for MRI inflammation (P = 0.001), synovitis (P =
      0.002) and BME (P = 0.003) compared to the other patients. CONCLUSION:
      Subclinical synovitis was observed in the small joints of ACPA-negative
      arthralgia patients, and especially in patients whose conditions progressed to
      clinically detectable arthritis. This finding suggests the presence of a
      preclinical phase in ACPA-negative RA. Further longitudinal studies of these
      lesions and patients are required to confirm this hypothesis.

PMID- 24721161
TI  - Cold blood versus crystalloid cardioplegia for myocardial protection in adult
      cardiac surgery: a meta-analysis of randomized controlled studies.
AB  - OBJECTIVE: The purpose of this article was to systematically review randomized
      controlled trials in which cold blood cardioplegia was compared with cold
      crystalloid cardioplegia for cardiac surgery. DESIGN: Correlation studies were
      searched independently in the EMBASE, MEDLINE and Cochrane library databases. The
      primary endpoints of interest were spontaneous sinus rhythm (SSR) after
      declamping, perioperative myocardial infarction (MI) and mortality (within 30
      days). SETTING: A hospital. PARTICIPANTS: Randomized controlled trials.
      INTERVENTION: A meta-analysis of 12 studies. MEASUREMENTS AND MAIN RESULTS: The
      12 included trials recruited a total of 2866 participants; 1357 patients received
      cold crystalloid cardioplegia, and 1509 patients received cold blood
      cardioplegia. The pooled analysis showed no significant difference favoring
      either cold crystalloid cardioplegia or cold blood cardioplegia in terms of
      spontaneous sinus rhythm (SSR) after declamping (789/1028 [76.75%] v 773/1025
      [75.41%], relative risk (RR) = 0.92 [0.76, 1.13], p = 0.43 with 6 studies
      included), mortality (within 30 days) (20/1335 [1.50%] v 24/1469 [1.63%],
      relative risk (RR) = 1.09 [0.62, 1.91], p = 0.77 with 11 studies included),
      atrial fibrillation (AF) (329/1043 [31.54%] v 365/1040 [35.10%], RR =0.90 [0.80,
      1.01], p = 0.08 with 6 studies included) or stroke (45/1114 [4.04%] v 20/1240
      [1.61%], RR = 2.18 [0.69, 6.93], p = 0.19 with 4 studies included). The aggregate
      data showed that the incidence of perioperative myocardial infarction was lower
      in patients who received cold blood cardioplegia (CB) (32/1310 [2.44%] v 17/1434
      [1.19%], RR = 2.30 [1.33, 3.98], p = 0.003 with 11 studies included).
      CONCLUSIONS: Cold blood cardioplegia reduced perioperative myocardial infarction
      when compared with cold crystalloid cardioplegia. No differences in the overall
      incidence rates of spontaneous sinus rhythm, mortality (within 30 days), atrial
      fibrillation or stroke were observed.

PMID- 24721162
TI  - Arginine residues within the DNA binding domain of STAT3 promote intracellular
      shuttling and phosphorylation of STAT3.
AB  - Acetylation-dependent inactivation of STAT1 can be mimicked by the exchange of
      its lysine residues K410 and K413 to glutamine residues. STAT3 harbors non
      acetylatable arginine moieties at the corresponding sites R414 and R417. It is
      unclear whether the mutation of these sites to glutamine residues antagonizes
      STAT3 activation. Here, we show that an arginine-glutamine-exchange at the STAT3
      moieties R414 and R417 (R414Q and R417Q) reduces cytokine-dependent tyrosine
      phosphorylation of STAT3. This inhibitory effect can be partially rescued by
      phosphatase inhibition. In addition, the R414Q and R417Q mutations enhance the
      nuclear accumulation of unphosphorylated STAT3. STAT3 R414Q and STAT3 R417Q show
      a reduced response to cytokine stimulation emanating from the plasma membrane.
      Moreover, these STAT3 mutants have no direct inhibitory effect on the cytokine
      induced activation of STAT1/STAT3-mediated gene expression. Since the mutations
      R414Q and R417Q reside within the STAT3 DNA binding domain (DBD), the STAT3 R414Q
      and R417Q mutants also lack intrinsic activity as transcription factors.
      Furthermore, in contrast to wild-type STAT3 they cannot compensate for a loss of
      STAT1 and they cannot promote STAT1/STAT3-dependent transcriptional activation.
      We further analyzed a STAT3 arginine-lysine-exchange mutant (R414K/R417K). This
      molecule mimics corresponding lysine residues found within the DBD of STAT1.
      Compared to wild-type STAT3, the STAT3 R414K/R417K mutant shows attenuated
      tyrosine phosphorylation and it is a less active transcription factor. In
      addition, STAT3 R414K/R417K is not activated by deacetylase inhibition. On the
      other hand, C-terminal acetylation of STAT3 is intact in STAT3 R414K/R417K. Our
      results suggest that the exchange of amino acid residues within the DBDs of
      STAT1/STAT3 affects their phosphorylation as well as their intracellular
      shuttling. 

PMID- 24721163
TI  - New sites of localisation of Pasteurella multocida B:2 in buffalo surviving
      experimental haemorrhagic septicaemia.
AB  - BACKGROUND: Haemorrhagic septicaemia (HS) is an acute septicaemic disease of
      buffalo and cattle caused by Pasteurella multocida B:2 and E:2. Field outbreaks
      of HS are known to result in localisation of bacteria in the tonsils of surviving
      buffalo, confirming that animals can become carriers and the role of respiratory
      tract in the transmission of the disease. This report describes additional sites
      of localisation of P. multocida B:2 in surviving buffalo following experimental
      induction of HS. RESULTS: Following P. multocida B:2 infection, all calves in
      group 1 and one calf in group 2 that was allowed to commingle with infected
      calves from group 1 were euthanised within 48 h. Pasteurella multocida B:2 was
      detected from the nasal and rectal swab samples on days 5 and 6 from the
      remaining calves in group 2. The first injection of dexamethasone into the
      carrier animals resulted in reemergence in samples from the nose, rectum and
      vagina. However, subsequent dexamethasone injections failed to re-activate P.
      multocida B:2. When surviving carrier calves in group 2 were euthanised at the
      end of the experiment, P. multocida B:2 was detected in the lungs and various
      organs of the respiratory, gastrointestinal and urinary tracts. CONCLUSIONS:
      Commingling naive buffalo calves with calves acutely infected with P. multocida
      B:2 resulted in carriers among surviving buffalo. Pasteurella was found in
      various organs of the respiratory, gastrointestinal and urinary tracts,
      suggesting their role in the pathogenesis of HS.

PMID- 24721164
TI  - Molecular epidemiologic and clinical characteristics of influenza B-associated
      complications among hospitalized patients during an outbreak in Taiwan.
AB  - OBJECTIVES: To study the resurgence of influenza B/Yam in Taiwan and summarize
      clinical findings of influenza B-associated complications among hospitalized
      patients, in particular the link between clinical and molecular epidemiologic
      characteristics. METHODS: Clinical information and isolates were collected
      through the national surveillance system of the Taiwan Centers for Disease
      Control. Potential risk factors associated with severe illness were analyzed.
      Antigenic and genetic analysis of representative hemagglutinin (HA) nucleotide
      sequences was performed. RESULTS: Of 326 patients admitted to the intensive care
      unit (ICU), 63.2% were aged <=18 years or >=65 years and 12.9% were adults aged
      19-49 years. Most of the cases had underlying medical conditions before
      admission, and more fatal cases had chronic medical conditions than those who
      convalesced in the ICU. Results of the phylogenetic analysis showed that the
      majority of isolates from fatal cases in Taiwan were in group 2 (represented by
      B/Massachusetts/2/2012-like) rather than group 3, which was the predominant group
      of strains circulating in other Asian countries. CONCLUSIONS: Our findings
      suggest a regional trend of influenza B viruses and showed that new phylogenetic
      lineages and antigenic variants emerging in neighboring countries were likely to
      be the progenitors of the epidemic strains in the following seasons.

PMID- 24721165
TI  - Impacts of a mass vaccination campaign against pandemic H1N1 2009 influenza in
      Taiwan: a time-series regression analysis.
AB  - OBJECTIVES: A multicenter, hospital-wide, clinical and epidemiological study was
      conducted to assess the effectiveness of the mass influenza vaccination program
      during the 2009 H1N1 influenza pandemic, and the impact of the prioritization
      strategy among people at different levels of risk. METHODS AND RESULTS: Among the
      34 359 medically attended patients who displayed an influenza-like illness and
      had a rapid influenza diagnostic test (RIDT) at one of the three participating
      hospitals, 21.0% tested positive for influenza A. The highest daily number of
      RIDT-positive cases in each hospital ranged from 33 to 56. A well-fitted multiple
      linear regression time-series model (R(2)=0.89) showed that the establishment of
      special community flu clinics averted an average of nine cases daily (p=0.005),
      and an increment of 10% in daily mean level of population immunity against pH1N1
      through vaccination prevented five cases daily (p<0.001). Moreover, the
      regression model predicted five-fold or more RIDT-positive cases if the mass
      influenza vaccination program had not been implemented, and 39.1% more RIDT
      positive cases if older adults had been prioritized for vaccination above school
      aged children. CONCLUSIONS: Mass influenza vaccination was an effective control
      measure, and school-aged children should be assigned a higher priority for
      vaccination than older adults during an influenza pandemic.

PMID- 24721166
TI  - Rationale for the use of the implantable Doppler probe based on 7 years'
      experience.
AB  - In head and neck microvascular reconstruction, a proportion of patients are at a
      higher risk of flap failure. These include salvage surgery after
      chemoradiotherapy, reconstruction for osteoradionecrosis and when difficulty is
      encountered in achieving flap perfusion intraoperatively. Several studies have
      shown that the Cook-Swartz Doppler (Cook Medical Inc, Bloomington, USA) enabled
      earlier detection of a compromised flap. We retrospectively reviewed
      microvascular reconstructions monitored with the Cook-Swartz implantable Doppler
      (2006-2012) and included patients' characteristics, comorbidity (American Society
      of Anesthesiologists' (ASA) grade), indication for operation, type of
      reconstruction, and indication for implantable Doppler. We also included details
      of surgical exploration, free flap salvage, and outcomes of flap salvage. These
      outcomes were compared with a group of low-risk patients (2005-2009) whose flaps
      were monitored clinically. A total of 75 free flaps in 73 patients were monitored
      with the implantable Doppler: 40 (53%) were in cases which required
      reconstruction following previous surgery/radiotherapy or flap perfusion
      difficulties, 10 (13%) buried flaps, 13 (17%) as routine flap monitors and 12
      (17%) for other indications. The false negative rate was 5%, sensitivity 67%, the
      false positive rate was 25%, and specificity was 95%. Higher risk flaps monitored
      with the doppler had a higher return to theatre rate, 21% compared with 4%
      (p<0.001) and flap failure rate, 7% compared with 1% (p=0.002). Salvage rates for
      free flaps were similar in both groups (62% compared with 60%, p=1.0). There is
      not enough evidence to suggest that the implantable doppler reduces the rate of
      failed flaps in routine low-risk cases, and its value in monitoring high-risk
      reconstructions require evaluation in a prospective randomised study. 

PMID- 24721167
TI  - A vertical incision for intraoral approach to a zygomaticomaxillary fracture.

PMID- 24721168
TI  - Place and time of death in patients treated with palliative intent for oral
      cancer.
AB  - Information about place and time of death can help patients, carers, general
      medical practitioners, and multi-professional teams to put palliation for oral
      cancer into context, particularly the aspirations of patients about where they
      die. Aintree Regional Maxillofacial Unit treated 487 consecutive patients for
      primary oral squamous cell carcinoma between 2006 and 2010. Mortality was
      ascertained from the Office for National Statistics. A total of 65 (13%) patients
      were treated with palliative intent, and median (IQR) survival was 4.3 months
      (2.1-8.0). The most common reasons for palliation were inoperability (33%) and
      extensive disease associated with serious comorbidity (18%). A total of 22 died
      in hospital, 14 in a hospice, 14 in their own home, 14 in a nursing, residential,
      or old people's home, and one elsewhere. Most patients given palliative care do
      not die in hospital and survival is short. Their needs and those of their carers
      can be better met through integrated care that is linked to the primary sector. 

PMID- 24721169
TI  - Cell viability after osteotomy and bone harvesting: comparison of piezoelectric
      surgery and conventional bur.
AB  - The aim of this study was to evaluate and compare the influence of a
      piezoelectric device versus a conventional bur on osteocyte viability and
      osteoblast and osteoclast activity using an in vivo mouse model. Osteotomies were
      created and bone grafts were harvested using either a conventional bur or a
      piezoelectric device; the resulting injuries and bone grafts were evaluated over
      an extended time-course using molecular and cellular assays for cell death (TUNEL
      assay), cell viability (4',6-diamidino-2-phenylindole (DAPI) staining), the onset
      of mineralization (alkaline phosphatase activity), and bone remodelling (tartrate
      resistant acid phosphatase activity). Osteotomies created with a piezoelectric
      device showed greater osteocyte viability and reduced cell death. Bone grafts
      harvested with a piezoelectric device exhibited greater short-term cell viability
      than those harvested with a bur, and exhibited slightly more new bone deposition
      and bone remodelling. The difference in response of osteocytes, osteoblasts, and
      osteoclasts to bone cutting via a bur and via a piezoelectric device is
      negligible in vivo. Given the improved visibility and the margin of safety
      afforded by a piezoelectric device, they are the instrument of choice when
      cutting or harvesting bone to preserve soft tissue. 

PMID- 24721170
TI  - Numerical estimation of hemolysis from the point of view of signal and system.
AB  - The power-law based models for predicting shear-induced hemolysis are widely used
      in the optimization design of blood-contacting devices. However, this category of
      models has fallen short of accuracy when compared with the results of the in
      vitro experiments. The aim of this study is to develop an alternative model from
      the point of view of signal and system. Under the action of constant shear
      stress, the released hemoglobin was regarded as the output of system, and the
      system function that characterized the resistance to hemolysis was derived from
      the power-law equation. Two state variables were introduced to adequately capture
      the history of the system. The proposed model takes into account another known
      empirical formula, the threshold equation, by setting a nonzero initial condition
      of the blood. By comparing the estimated results with the published experimental
      data, it showed that the accuracy of the proposed model was notably improved.
      Furthermore, the analysis in frequency domain indicated that the damage
      contribution of the time-varying shear stress decreased with the increase of
      frequency. As the frequency domain analysis is important in many fields, it may
      play a role in the estimation of hemolysis in the future. 

PMID- 24721171
TI  - Highly automated electron energy-loss spectroscopy elemental quantification.
AB  - A model-based fitting algorithm for electron energy-loss spectroscopy spectra is
      introduced, along with an intuitive user-interface. As with Verbeeck & Van Aert,
      the measured spectrum, rather than the single scattering distribution, is fit
      over a wide range. An approximation is developed that allows for accurate
      modeling while maintaining linearity in the parameters that represent elemental
      composition. Also, a method is given for generating a model for the low-loss
      background that incorporates plural scattering. Operation of the user-interface
      is described to demonstrate the ease of use that allows even nonexpert users to
      quickly obtain elemental analysis results. 

PMID- 24721172
TI  - Nemo-like kinase (NLK) negatively regulates NF-kappa B activity through
      disrupting the interaction of TAK1 with IKKbeta.
AB  - Stringent negative regulation of the transcription factor NF-kappaB is essential
      for maintaining cellular stress responses and homeostasis. However, the tight
      regulation mechanisms of IKKbeta are still not clear. Here, we reported that nemo
      like kinase (NLK) is a suppressor of tumor necrosis factor (TNFalpha)-induced NF
      kappaB signaling by inhibiting the phosphorylation of IKKbeta. Overexpression of
      NLK largely blocked TNFalpha-induced NF-kappaB activation, p65 nuclear
      localization and IkappaBalpha degradation; whereas genetic inactivation of NLK
      showed opposing results. Mechanistically, we identified that NLK interacted with
      IkappaB kinase (IKK)-associated complex, which in turn inhibited the assembly of
      the TAK1/IKKbeta and thereby, diminished the IkappaB kinase phosphorylation. Our
      results indicate that NLK functions as a pivotal negative regulator in TNFalpha
      induced activation of NF-kappaB via disrupting the interaction of TAK1 with
      IKKbeta. 

PMID- 24721173
TI  - Essentials of negotiating for employment in a changing environment.
AB  - Evolving changes in health care in the United States are causing new graduates
      and self-employed physicians to consider employment with large groups and health
      systems. Familiarity with the principles, proper conduct, and mechanics of
      negotiating an employment agreement will be important for vascular surgeons
      making such a decision. The various components of compensation packages and
      contract language need to be critically evaluated. To facilitate an understanding
      of the complexities involved in employment contracts, strategies to avoid making
      negotiating mistakes are discussed. 

PMID- 24721174
TI  - Routine use of completion imaging after infrainguinal bypass is not associated
      with higher bypass graft patency.
AB  - BACKGROUND: Significant variability exists in completion imaging (CIM) after
      infrainguinal lower extremity bypass (LEB). We evaluated the use of CIM and
      compared graft patency in patients treated by surgeons who performed routine CIM
      vs those who performed selective CIM. METHODS: We reviewed the Vascular Study
      Group of New England database (2003-2010) and assessed the use of CIM
      (angiography or duplex ultrasound) among patients undergoing LEB. The surgeon
      specific CIM strategy was categorized as routine (>=80% of LEBs) vs selective
      (<80% of LEBs). Exclusion criteria included acute limb ischemia, bilateral
      procedures, and surgeon volume <10 cases per study period. Primary graft patency
      at discharge and at 1 year was analyzed on the basis of CIM use and surgeon
      specific CIM strategy. Multivariable analyses were performed using Poisson
      regression. RESULTS: Among 2032 LEB procedures performed by 48 surgeons, CIM was
      used in 1368 cases (67.3%). CIM was performed in 72% of autogenous LEBs and 52%
      of prosthetic grafts. Dialysis (odds ratio [OR], 1.7; 95% confidence interval
      [CI], 1.1-2.6; P = .01), elective LEB (OR, 2.6; 95% CI, 1.4-4.8; P = .002), great
      saphenous vein conduit (OR, 2.0; 95% CI, 1.6-2.5; P < .001), and tibial or pedal
      target artery (OR, 1.8; 95% CI, 1.4-2.3; P < .001) were associated with CIM use.
      In multivariate models, CIM was not associated with improved primary graft
      patency at discharge (OR, 1.1; 95% CI, 0.7-1.7; P = .64) or at 1 year (OR, 0.9;
      95% CI, 0.7-1.2; P = .47). Sixteen surgeons (33%) were routine users and 32 (67%)
      were selective users of CIM. Among patients of routine vs selective CIM users,
      primary graft patency at discharge and at 1 year was 96% vs 94% (P = .21) and 68%
      vs 72% (P = .09), respectively. In multivariate analysis, routine or selective
      CIM strategy was not associated with improved discharge (rate ratio, 0.8; 95% CI,
      0.6-1.1; P = .31) or 1-year (rate ratio, 1.1; 95% CI, 0.9-1.2; P = .56) graft
      patency. CONCLUSIONS: In our observational cohort, CIM does not improve short
      term and 1-year bypass graft patency in infrainguinal LEB. The surgeon-specific
      strategy of selective CIM after LEB has outcomes comparable to those of routine
      CIM.

PMID- 24721175
TI  - A comparison of open and endovascular revascularization for chronic mesenteric
      ischemia in a clinical decision model.
AB  - OBJECTIVE: Open revascularization (OR) has been the treatment of choice for
      chronic mesenteric ischemia (CMI) for many years, but endovascular
      revascularization (EV) has been increasingly used with good short-term results.
      In this study, we evaluated the comparative effectiveness and cost-effectiveness
      of EV and OR in patients with CMI refractory to conservative management. METHODS:
      A Markov-state transition model was developed using TreeAge Pro 2012 (TreeAge
      Inc, Williamstown, Mass) to simulate a hypothetical cohort of 10,000 65-year-old
      female patients with CMI requiring treatment with either OR or EV. Data for the
      model, including perioperative and long-term overall mortality risks, disease
      specific mortality risks, complications, and reintervention and patency rates,
      were retrieved from original studies and systematic reviews about CMI. Costs were
      analyzed with the 2013 Medicare database. Outcomes evaluated were quality
      adjusted life-years (QALYs), costs from the health care perspective, and the
      incremental cost-effectiveness ratio. Extensive sensitivity analyses were
      performed and different clinical scenarios evaluated. Probabilistic sensitivity
      analysis was performed to assess robustness of the model. RESULTS: For a
      reference-case 65-year-old female patient with CMI and an average risk for
      operation, EV is preferred with 10.03 QALYs (95% credibility interval [CI], 9.76
      10.29) vs 9.59 after OR (95% CI, 9.29-9.87). The difference is comparable to 5
      months in perfect health: 0.44 QALY (95% CI, 0.13-0.76). For 65-year-old men,
      this was 8.71 QALYs (95% CI, 8.48-8.94) for EV vs 8.42 (95% CI, 8.14-8.63) for
      OR. Sensitivity analysis showed that for younger patients, EV results in a higher
      increase in QALYs compared with older patients. Total expected reinterventions
      per patient are 1.70 for EV vs 0.30 for OR. Total expected health care costs for
      the reference-case patient were $39,942 (95% CI, $28,509-$53,380) for OR and
      $38.217 (95% CI, $29,329-$48,309) for EV. For men, this was $39,375 (95% CI,
      $28,092-$52,853) for OR and $35,903 (95% CI, $27,685-$45,597) for EV. For
      patients younger than 60 years, EV is a more expensive treatment strategy
      compared with OR, but with an incremental cost-effectiveness ratio for EV of less
      than $60,000/QALY. For patients 60 years and older, EV dominated OR as
      preferential treatment because effectiveness was higher than for OR and costs
      were lower. CONCLUSIONS: The results of this decision analysis model suggest that
      EV is favored over OR for patients with CMI in all age groups. Although EV is
      associated with more expected reinterventions, EV appears to be cost-effective
      for all age groups.

PMID- 24721176
TI  - Discussion.

PMID- 24721177
TI  - Cross-enhancement of ANGPTL4 transcription by HIF1 alpha and PPAR beta/delta is
      the result of the conformational proximity of two response elements.
AB  - BACKGROUND: Synergistic transcriptional activation by different stimuli has been
      reported along with a diverse array of mechanisms, but the full scope of these
      mechanisms has yet to be elucidated. RESULTS: We present a detailed investigation
      of hypoxia-inducible factor (HIF) 1 dependent gene expression in endothelial
      cells which suggests the importance of crosstalk between the peroxisome
      proliferator-activated receptor (PPAR) beta/delta and HIF signaling axes. A
      migration assay shows a synergistic interaction between these two stimuli, and we
      identify angiopoietin-like 4 (ANGPTL4) as a common target gene by using a
      combination of microarray and ChIP-seq analysis. We profile changes of histone
      marks at enhancers under hypoxia, PPARbeta/delta agonist and dual stimulations
      and these suggest that the spatial proximity of two response elements is the
      principal cause of the synergistic transcription induction. A newly developed
      quantitative chromosome conformation capture assay shows the quantitative change
      of the frequency of proximity of the two response elements. CONCLUSIONS: To the
      best of our knowledge, this is the first report that two different transcription
      factors cooperate in transcriptional regulation in a synergistic fashion through
      conformational change of their common target genes.

PMID- 24721178
TI  - The power of nursing: guiding patients through a journey of uncertainty.
AB  - PURPOSE: The objective of this qualitative study was to understand the
      experiences of oncology nurses in patient counseling and support services in the
      ambulatory care setting. METHODS AND SAMPLE: A qualitative study was conducted
      using grounded theory methods. Data were generated through four focus group
      interviews with 21 oncology nurses currently providing counseling and support
      services for cancer patients in Japan. The content was analyzed based on a
      constant comparison approach. RESULTS: The power of nursing was identified
      through three themes: connecting with the patient (shared needs); personalized
      coordination (shared action); and realizing the patient's potential
      (reassurance). Oncology nurses should guide patients through the uncertain cancer
      trajectory by identifying patients' true needs based on an established
      relationship, providing personalized coordination, and developing their
      potential. Patient-centered care can be provided in non-physical care settings
      such as counseling and support services. CONCLUSIONS: Our study describes the
      uniqueness and significance of nursing, and provides insights into realizing the
      full potential of nurses. This conceptual model can be used as a guide for
      practice and an educational tool to build professional identity of nurses.
      Oncology nurses can take a leadership role in enhancing the visibility of the
      nurses in multidisciplinary environments.

PMID- 24721179
TI  - The assessment of health-related quality of life and related factors in Chinese
      elderly patients undergoing chemotherapy for advanced cancer: a cross-sectional
      study.
AB  - PURPOSE OF THE RESEARCH: (i) To assess the health-related quality of life (HRQOL)
      and analyse the potential contributing factors of HRQOL in elderly cancer
      patients in China; and (ii) to evaluate the possible correlation between the
      Medical Outcomes 36-Item Short Form Health Survey (SF-36) and the European
      Organization for Research and Treatment of Cancer, quality of life questionnaire
      (EORTC QLQ-C30). METHODS AND SAMPLE: A total of 109 elderly patients undergoing
      chemotherapy with advanced cancer completed a survey assessing HRQOL, anxiety and
      depression. HRQOL was measured by SF-36 and EORTC QLQ-C30. Anxiety and
      depression, was measured by the Hospital Anxiety and Depression Scale (HADS). KEY
      RESULTS: Scales pertaining to role functioning, including SF-36 role physical
      (25.92 +/- 37.10) and role emotional (36.12 +/- 43.50), EORTC QLQ-C30 role
      functioning (46.94 +/- 36.86), were the worst domains of SF-36 and EORTC QLQ-C30
      respectively. Financial impact (55.77 +/- 36.55) and fatigue (46.18 +/- 26.48)
      were the top two highest scores among all nine symptom-related scales of EORTC
      QLQ C-30. The correlation matrix of SF-36 versus EORTC QLQ-C30 showed that, in
      general, there was good correlation between scales pertaining to the same health
      domain, and low correlation was observed between scales pertaining to different
      domains. CONCLUSIONS: The findings of this study highlight role functioning,
      financial impact, fatigue, anxiety, and depression as areas where elderly cancer
      patients could most benefit from intervention. These findings also call attention
      to HRQOL and its related factors in elderly cancer patients. Interventions to be
      developed for improving HRQOL in cancer patients are highly recommended.

PMID- 24721180
TI  - Having a sibling as donor: patients' experiences immediately before allogeneic
      hematopoietic stem cell transplantation.
AB  - BACKGROUND: Allogeneic hematopoietic stem cell transplantation (HSCT) offers a
      potential cure for a variety of diseases but is also associated with significant
      risks. With HSCT the donor is either a relative, most often a sibling, or an
      unrelated registry donor. PURPOSE: The aim was to explore patients' experiences,
      immediately before transplantation, regarding having a sibling as donor. METHOD:
      Ten adult patients with sibling donors were interviewed before admission for
      HSCT. The interviews were digitally recorded, transcribed verbatim and subjected
      to qualitative content analysis. RESULTS: The main theme Being in no man's land
      is a metaphor for the patients' complex situation with its mixture of emotions
      and thoughts prior to transplantation. The three subthemes Trust in the sibling
      donor, Concern about others and Loss of control cover the various experiences.
      The patient's experiences are influenced by their personal situation and the
      quality of the relationship with the sibling donor. While patients feel secure in
      having a sibling donor, they are dependent for their survival on the cell
      donation and feel responsible for the donor's safety during donation. These
      emotions intensify the patients' sense of dependency and loss of control.
      CONCLUSIONS: In caring for HSCT patients the nurses should be aware of the
      complexity of the patients' situation and keep in mind that having a sibling
      donor might imply extra pressure, including a sense of responsibility. Caring for
      both patients and sibling donors optimally is a challenge, which needs further
      improvement and exploration.

PMID- 24721181
TI  - Is regression through origin useful in external validation of QSAR models?
AB  - The external validation of QSAR models is crucial to ensure their reliability for
      assessing new chemicals. The most widely used criteria for external validations,
      which has been applied in hundreds of more recent QSAR studies are the Golbraikh
      Tropsha and Roy methods which these criteria are based on the regression through
      origin (RTO). In this study, the calculations of the deviation parameters such as
      absolute errors are used for ascertaining the difference between training and
      test sets to evaluate the prediction capability of the models. However, these
      results were not in a good agreement with the proposed criteria for external
      validation and there is an inconsistency in the definition and calculation of
      r(2) of RTO and therefore the constructed criteria based on RTO is not optimal.
      Instead, the calculation of model errors for training and test sets and compare
      them, provide a possible reliable method to external validation of QSAR models. 

PMID- 24721182
TI  - Mini-plate versus Kirschner wire internal fixation for treatment of metacarpal
      and phalangeal fractures in Chinese Han population: a meta-analysis.
AB  - OBJECTIVES: This meta-analysis aimed to compare the therapeutic effect of mini
      plate versus Kirschner wire (K-wire) internal fixation on the treatment of
      metacarpal and phalangeal fractures among Chinese Han population. METHODS:
      Databases of China National Knowledge Infrastructure (CNKI), Wanfang, Chinese
      VIP, PubMed, and Embase were retrieved for studies on mini-plate (case group)
      versus K-wire (control group) internal fixation for the treatment of metacarpal
      and phalangeal fractures among Chinese Han population. The odds ratio (OR) and
      standardized mean difference (SMD) at 95% confidence interval (CI) were used for
      estimating the effects of dichotomous data and continuous data, respectively. All
      statistical analyses were performed by Review Manager 5.2 software. RESULTS: A
      total of 18 studies involving 1,375 metacarpal or phalangeal fracture patients
      (709 cases and 666 controls) were included in the meta-analysis. There were
      significant differences in fracture healing time (SMD = -1.28; 95% CI: -1.81, 
      0.76), postoperative infection rate (OR = 0.25; 95% CI: 0.16, 0.39), complication
      incidence (OR = 0.24; 95% CI: 0.15, 0.38), and surgery time (SMD = 1.57; 95% CI:
      0.76, 2.37) between the case and the control group, while no significant
      difference was found in hospital stays between these two groups (SMD = 0.43; 95%
      CI: -0.34, 1.20; P = 0.27). CONCLUSIONS: For the treatment of metacarpal or
      phalangeal fracture among Chinese Han population, mini-plate has advantages of
      shorter healing time and lower infection rate and complication incidence compared
      with K-wire internal fixation, while a longer surgery time than K-wire. In
      conclusion, mini-plate is prior than K-wire internal fixation for the treatment
      of metacarpal or phalangeal fracture among Chinese Han population.

PMID- 24721183
TI  - A contemporary review of mechanical circulatory support.
AB  - Mechanical circulatory support has seen numerous advances in the recent years,
      with important observations made to guide patient selection for the therapy,
      indications for use, and management of devices after implantation. There is rapid
      growth in the use of left ventricular assist device therapy (LVAD) for advanced
      heart failure, with a movement to pursue device intervention earlier in the
      disease spectrum before comorbidities escalate. With this increase in LVAD use
      have come new challenges, including unanticipated adverse events and high
      readmission rates. Simultaneously, complications encountered during LVAD support
      and an increased number of patients supported with a goal for transplant have had
      an important effect on the allocation of cardiac allografts. Still, the field
      continues to evolve and address these challenges in systematic fashion to provide
      novel solutions and meet the needs of a growing population with advanced heart
      failure. This has led to an extensive body of literature, ranging from case
      reports to multicenter clinical trials, which will enhance the future of LVAD
      technology and patient outcomes. This review summarizes important publications in
      mechanical circulatory support during the past 24 months. 

PMID- 24721184
TI  - Did liberalising bar hours decrease traffic accidents?
AB  - Legal bar closing times in England and Wales have historically been early and
      uniform. Recent legislation liberalised closing times with the object of reducing
      social problems thought associated with drinking to "beat the clock." Indeed,
      using both difference in difference and synthetic control approaches we show that
      one consequence of this liberalisation was a decrease in traffic accidents. This
      decrease is heavily concentrated among younger drivers. Moreover, we provide
      evidence that the effect was most pronounced in the hours of the week directly
      affected by the liberalisation: late nights and early mornings on weekends. This
      evidence survives a series of robustness checks and suggests at least one
      socially positive consequence of extending bar hours. 

PMID- 24721185
TI  - Combining the effects of conventional risk factors and environmental triggering
      factors while studying seasonality in acute myocardial infarction.

PMID- 24721186
TI  - Taurine: the comeback of a neutraceutical in the prevention of retinal
      degenerations.
AB  - Taurine is the most abundant amino acid in the retina. In the 1970s, it was
      thought to be involved in retinal diseases with photoreceptor degeneration,
      because cats on a taurine-free diet presented photoreceptor loss. However, with
      the exception of its introduction into baby milk and parenteral nutrition,
      taurine has not yet been incorporated into any commercial treatment with the aim
      of slowing photoreceptor degeneration. Our recent discovery that taurine
      depletion is involved in the retinal toxicity of the antiepileptic drug
      vigabatrin has returned taurine to the limelight in the field of neuroprotection.
      However, although the retinal toxicity of vigabatrin principally involves a
      deleterious effect on photoreceptors, retinal ganglion cells (RGCs) are also
      affected. These findings led us to investigate the possible role of taurine
      depletion in retinal diseases with RGC degeneration, such as glaucoma and
      diabetic retinopathy. The major antioxidant properties of taurine may influence
      disease processes. In addition, the efficacy of taurine is dependent on its
      uptake into retinal cells, microvascular endothelial cells and the retinal
      pigment epithelium. Disturbances of retinal vascular perfusion in these retinal
      diseases may therefore affect the retinal uptake of taurine, resulting in local
      depletion. The low plasma taurine concentrations observed in diabetic patients
      may further enhance such local decreases in taurine concentration. We here review
      the evidence for a role of taurine in retinal ganglion cell survival and studies
      suggesting that this compound may be involved in the pathophysiology of glaucoma
      or diabetic retinopathy. Along with other antioxidant molecules, taurine should
      therefore be seriously reconsidered as a potential treatment for such retinal
      diseases. 

PMID- 24721187
TI  - Association between human papillomavirus (HPV) and oesophageal squamous cell
      carcinoma: a meta-analysis.
AB  - SUMMARY: The oncogenic potential of human papillomaviruses (HPV) is well known in
      the context of cervical carcinoma; however, their role in the development of
      oesophageal squamous cell carcinoma (OSCC) is less clear. We aimed to determine
      the extent of the association between HPV infection and OSCC. A comprehensive
      literature search found 132 studies addressing HPV and OSCC in human cases, and a
      meta-analysis was performed using a random-effects model. There was evidence of
      an increased risk of OSCC in patients with HPV infection [odds ratio (OR) 2.69,
      95% confidence interval (CI) 2.05-3.54]. The prevalence of HPV in OSCC was found
      to be 24.8%. There was an increased risk associated with HPV-16 infection (OR
      2.35, 95% CI 1.73-3.19). Subgroup analyses showed geographical variance, with
      Asia (OR 2.94, 95% CI 2.16-4.00), and particularly China (OR 2.85, 95% CI 2.05
      3.96) being high-risk areas. Our results confirm an increase in HPV infection in
      OSCC cases.

PMID- 24721188
TI  - 3MTM Molecular detection system versus MALDI-TOF mass spectrometry and molecular
      techniques for the identification of Escherichia coli 0157:H7, Salmonella spp.
      &Listeria spp.
AB  - The aim of this study was to compare standard selective plating, conventional PCR
      (16S rRNA and species specific primers), MALDI-TOF MS and the 3MTM Molecular
      Detection System for the routine detection of the pathogens Listeria, Salmonella
      and Escherichia coli 0157:H7 in wastewater and river water samples. MALDI-TOF MS
      was able to positively identify 20/21 (95%) of the E. coli isolates obtained at
      genus and species level, while 16S rRNA sequencing only correctly identified 6/21
      (28%) as E. coli strains. None of the presumptive positive Listeria spp. and
      Salmonella spp. isolates obtained by culturing on selective media were positively
      identified by MALDI-TOF and 16S rRNA analysis. The species-specific E. coli
      0157:H7 PCR described in this present study, was not able to detect any E. coli
      0157:H7 strains in the wastewater and river water samples analysed. However, E.
      coli strains, Listeria spp., L. monocytogenes and Salmonella spp. were detected
      using species specific PCR. Escherichia coli 0157:H7, Listeria spp. and
      Salmonella spp. were also sporadically detected throughout the sampling period in
      the wastewater and river water samples analysed by the 3MTM Molecular Detection
      System. MALDI-TOF MS, which is a simple, accurate and cost-effective detection
      method, efficiently identified the culturable organisms, while in the current
      study both species specific PCR (Listeria spp. and Salmonella spp.) and 3MTM
      Molecular Detection System could be utilised for the direct routine analysis of
      pathogens in water sources. 

PMID- 24721189
TI  - Endothelial microparticles as conveyors of information in atherosclerotic
      disease.
AB  - Endothelial microparticles (EMPs) are complex submicron membrane-shed vesicles
      released into the circulation following endothelium cell activation or apoptosis.
      They are classified as either physiological or pathological, with anticoagulant
      or pro-inflammatory effects respectively. Endothelial dysfunction caused by
      inflammation is a key initiating event in atherosclerotic plaque formation.
      Athero-emboli, resulting from ruptured carotid plaques are a major cause of
      stroke. Current clinical techniques for arterial assessment, angiography and
      carotid ultrasound, give accurate information about stenosis but limited evidence
      on plaque composition, inflammation or vulnerability; as a result, patients with
      asymptomatic, or fragile carotid lesions, may not be identified and treated
      effectively. There is a need to discover novel biomarkers and develop more
      efficient diagnostic approaches in order to stratify patients at most risk of
      stroke, who would benefit from interventional surgery. Increasing evidence
      suggests that EMPs play an important role in the pathogenesis of cardiovascular
      disease, acting as a marker of damage, either exacerbating disease progression or
      triggering a repair response. In this regard, it has been suggested that EMPs
      have the potential to act as biomarkers of disease status. In this review, we
      will present the evidence to support this hypothesis and propose a novel concept
      for the development of a diagnostic device that could be implemented in the
      clinic. 

PMID- 24721191
TI  - Validation of the Italian version Inventory of Complicated Grief (ICG): a study
      comparing CG patients versus bipolar disorder, PTSD and healthy controls.
AB  - BACKGROUND: A minority (9%-20%) of bereaved individuals experience symptoms of
      persistent intense grief associated with significant distress and impairment.
      This recently identified distinct post-loss syndrome has been variously named
      complicated grief, prolonged grief disorder, traumatic grief and persistent
      complex bereavement disorder. The Inventory of Complicated Grief (ICG) is a self
      report instrument used to reliably identify this syndrome. We undertook a study
      to: 1) validate the Italian version of the ICG; 2) examine its performance in a
      clinical of bereaved individuals with complicated grief, post-traumatic stress
      disorder, bipolar disorder and healthy controls. METHODS: Study participants
      included 171 bereaved individuals clinically diagnosed with complicated grief
      (n=64); post-traumatic stress disorder (n=72); bipolar disorder (n=35) and 58
      bereaved healthy controls. Assessments included the Structured Clinical Interview
      for DSM-IV Axis I disorders (SCID-I/P) and the Italian version of the ICG.
      RESULTS: The mean total ICG score was significantly different among the study
      groups [F(3.228)=94.19, p<.001]. Post-hoc Games-Howell comparisons indicated
      significantly higher scores in complicated grief patients with respect to the
      other three groups and significantly lower scores in healthy controls compared to
      all other participants. The scale demonstrated a high level of internal
      consistency: Cronbach's alpha value for the whole sample was 0.947. Factor
      analyses demonstrated a single-factor solution. CONCLUSIONS: This study provides
      evidence of the validation of the Italian version of the ICG, tested in a large
      and well-characterized clinical help-seeking population. These data further
      support the existence of a unique grief-related syndrome different from bipolar
      and post-traumatic stress disorders.

PMID- 24721190
TI  - Mediterranean diet and carotid atherosclerosis in the Northern Manhattan Study.
AB  - OBJECTIVE: Adherence to a Mediterranean-style diet (MeDi) may protect against
      clinical vascular events by reducing atherosclerosis, but data is limited. This
      is the first observational study of the association between MeDi adherence and
      carotid plaque thickness and area. METHODS: The study included 1374 participants
      of the population-based Northern Manhattan Study with diet assessed and carotid
      intima-media thickness (cIMT) and plaque measured using B-mode ultrasound (mean
      age 66 +/- 9 years, 60% female, 60% Hispanic, 18% White, 19% Black). A MeDi
      adherence score (range = 0-9, 9 representing maximal adherence) was examined
      continuously and in quintiles (3/4/5/6-9 vs. 0-2). RESULTS: Mean cIMT = 0.9 +/-
      0.1 mm and 57% had plaque (median plaque thickness = 1.5 mm, 75th percentile =
      2.2; median plaque area = 4.2 mm(2), 75th percentile = 15.8). There was no
      association between MeDi and cIMT or plaque presence. MeDi adherence was
      inversely associated with the 75th percentile of plaque thickness and median of
      plaque area in quantile regression analyses. These associations persisted after
      controlling for demographics, smoking, physical activity, and total energy
      consumption (effect of a 1-point increase in MeDi score on the 75th percentile of
      plaque thickness = -0.049 mm, p = 0.03; median of plaque area = -0.371 mm(2), p =
      0.03), and when additionally controlling for vascular disease biomarkers,
      medication use, BMI, and previous cardiac disease. The protective associations
      appeared strongest for those with a MeDi score of 5 (4th quintile) vs. 0-2
      (bottom quintile). Differential effects of a MeDi on plaque thickness and area
      across race/ethnic groups was suggested. CONCLUSIONS: Moderate and strict
      adherence to a MeDi may protect against a higher burden of carotid
      atherosclerotic plaque, which may mediate the protection against clinical
      vascular events. Efforts to improve adherence to a MeDi are critical to reducing
      the burden of atherosclerotic disease.

PMID- 24721192
TI  - Validation and psychometric properties of the German Capability for Suicide
      Questionnaire.
AB  - OBJECTIVE: Our study aimed at the validation of the newly developed German
      Capability for Suicide Questionnaire, the GCSQ. It is supposed to assess both
      fearlessness of death and pain tolerance, both facets of the acquired capability
      to commit suicide as postulated by the interpersonal theory of suicide. METHODS:
      This cross-sectional study was conducted on two clinical (n=424) and an online
      sample (n=532). Factor structure, convergent and discriminant validity,
      predictive validity as well as test-retest reliability were investigated.
      RESULTS: Two factors-"Fearlessness of Death" and "Pain Tolerance"-were derived.
      One item, the "perceived capability" item, assesses the subject's self-perception
      of acquired capability. Both subscales and the "perceived capability"-item
      demonstrate good construct validity and a high test-retest reliability.
      Fearlessness of death proves to be predictive for the occurrence of suicidal
      behaviors, whereas the importance of pain tolerance for suicidal behaviors was
      not confirmed. The subject's perception of his own capability is of high
      predictive value for both attempt status and suicidal behaviors. CONCLUSION: The
      GCSQ seems to be a useful measure of pain tolerance, fearlessness of death and
      the self-perception of acquired capability of suicide.

PMID- 24721193
TI  - Direct expansion of chondrocytes in a dynamic three-dimensional culture system:
      overcoming dedifferentiation effects in monolayer culture.
AB  - Maintenance of the chondrocyte phenotype during cell culture to successful
      transplantation of cartilage is highly challenging. However, the question of the
      optimal method of isolation and expansion of chondrocytes for tissue engineering
      has not previously been investigated in detail. The present study investigates
      the possibility of improved in vitro maturation of chondrocytes through a method
      of cell duplication that does not subject chondrocytes to dedifferentiation. The
      culture chamber of the bioreactor was designed with an internal geometry that
      mimicked that of a ball-and-socket joint. The shear stresses exerted on the
      surface of the bioreactor chamber wall by a peristaltic pump operating at flow
      rates of 2 mL/min were simulated by computational fluid dynamics (CFD) modeling.
      Small pieces (5 mm) of calf nasal septum cartilage were prepared and exposed to
      trypsin and 0.2% collagenase type II in Dulbecco's modified Eagle's medium
      (DMEM), which was then replaced with unsupplemented DMEM. The cells were
      harvested and then immediately seeded into alginate scaffolds. All cell-seeded
      scaffolds were cultured for 3-5 days in flasks, then transferred to the
      bioreactor and dynamically cultured for 3-5 days under direct perfusion with 2
      mL/min DMEM. After culture in the bioreactor, all cell-seeded scaffolds were
      fixed in Bouin fixative, dehydrated, cleared, and then embedded in paraffin wax.
      Sections of 5-7 MUm were cut and stained with several histochemical staining
      methods. The results of CFD modeling indicated peak velocity and maximum wall
      shear stress were 3.406 * 10(-3) m/s and 0.0482 dyn/cm(2) (1 Pa = 10 dyn/cm(2) ),
      respectively. Histological examination of chondrocytes cultured in the bioreactor
      revealed evidence of cartilage-like tissue with lacuna and chondron formation.
      The cartilage-like matrix had accumulated within the lumen of clusters of round
      mature chondrocytes, with the cells surrounding the metachromatic territorial
      matrix-staining strongly with toluidine blue. Sections stained with the
      hematoxylin/safranin O/fast green and Alcian blue/nuclear fast red methods show
      sulfated glycosaminoglycans in the matrix (produced by the chondrocytes) as
      intense red and blue, respectively. The findings of the present study indicate
      that incubation in DMEM supplemented with enzymes followed by explant isolation
      and culture in a bioreactor is the optimal method for the direct expansion of
      chondrocytes for cartilage tissue engineering.

PMID- 24721194
TI  - Operant ethanol self-administration in ethanol dependent mice.
AB  - While rats have been predominantly used to study operant ethanol self
      administration behavior in the context of dependence, several studies have
      employed operant conditioning procedures to examine changes in ethanol self
      administration behavior as a function of chronic ethanol exposure and withdrawal
      experience in mice. This review highlights some of the advantages of using
      operant conditioning procedures for examining the motivational effects of ethanol
      in animals with a history of dependence. As reported in rats, studies using
      various operant conditioning procedures in mice have demonstrated significant
      escalation of ethanol self-administration behavior in mice rendered dependent via
      forced chronic ethanol exposure in comparison to nondependent mice. This paper
      also presents a summary of these findings, as well as suggestions for future
      studies. 

PMID- 24721196
TI  - Minimally invasive epicardial left ventricular lead placement in a case of
      massive pleural adhesion.
AB  - BACKGROUND: In cases of intravenous placement failure of the left ventricular
      (LV) lead for cardiac resynchronisation therapy (CRT) and obliteration of the
      left pleural space, the alternative approach of transthoracic placement by video
      assisted thoracoscopic surgery (VATS) is difficult and not commonly practiced.
      METHODS: Here, we present a simple technique for transthoracic introduction of an
      epicardial LV lead using a wound retractor (ALEXIS) in a patient with heart
      failure. This wound retractor enables atraumatic tissue retraction without rib
      spreading, an optimal direct view in the pleural space for surgical pleurolysis
      and a high degree of safety for the patient. RESULTS: No perioperative
      complications occurred. The tube drainage was removed on the second postoperative
      day, and the patient was discharged on the third postoperative day. CONCLUSIONS:
      The decided advantage of this new method is the lack of any need for rib
      spreading using a mechanical retractor. Especially in patients with a history of
      open-heart surgery (including internal mammary artery bypass grafting and/or
      revascularisation of the left lateral wall) or known pleural adhesions (e.g.,
      pleuritis or lung operations), the described technique provides a rapid and save
      access with minimal surgical effort and greater safety.

PMID- 24721195
TI  - Intermittent ethanol access schedule in rats as a preclinical model of alcohol
      abuse.
AB  - One of the major challenges in preclinical studies of alcohol abuse and
      dependence remains the development of paradigms that will elicit high ethanol
      intake and mimic the progressive transition from low or moderate social drinking
      to excessive alcohol consumption. Exposure of outbred rats to repeated cycles of
      free-choice ethanol intake and withdrawal with the use of intermittent access to
      20% ethanol in a 2-bottle choice procedure (IA2BC) has been shown to induce a
      gradual escalation of voluntary ethanol intake and preference, eventually
      reaching ethanol consumption levels of 5-6 g/kg/24 h, and inducing
      pharmacologically relevant blood ethanol concentrations (BECs). This procedure
      has recently been gaining popularity due to its simplicity, high validity, and
      reliable outcomes. Here we review experimental and methodological data related to
      IA2BC, and discuss the usefulness and advantages of this procedure as a valuable
      pre-training method for initiating operant ethanol self-administration of high
      ethanol intake, as well as conditioned place preference (CPP). Despite some
      limitations, we provide evidence that IA2BC and related operant procedures
      provide the possibility to operationalize multiple aspects of alcohol abuse and
      addiction in a rat model, including transition from social-like drinking to
      excessive alcohol consumption, binge drinking, alcohol seeking, relapse, and
      neuroadaptations related to excessive alcohol intake. Hence, IA2BC appears to be
      a useful and relevant procedure for preclinical evaluation of potential
      therapeutic approaches against alcohol abuse disorders. 

PMID- 24721197
TI  - A multicenter survey of clinical experiences with perampanel in real life in
      Germany and Austria.
AB  - Perampanel (PER) has been approved by the European Medicines Agency (EMA) for
      adjunctive treatment of patients with partial-onset seizures from age 12 years
      on. It has been introduced to the market in Germany and Austria in 2012. This
      cross-sectional observational study summarizes the clinical experience of nine
      centers with adjunctive PER. Patients were consecutively followed from the
      initiation of PER on. Only patients with a minimum observational period of six
      months (in case of ongoing treatment) were recruited. Efficacy data reflect the
      preceding three months at last observation, tolerability data were assessed at
      the last observation carried forward. 281 patients were included. After six
      months 169 were still on PER so that a retention rate of 60% resulted. 43
      patients were seizure-free for the preceding 3 months (15%). Overall incidence of
      adverse events was 52.0%. The leading adverse events were somnolence (24.6%) and
      dizziness (19.6%) followed by ataxia (3.9%), aggression (2.8%), nausea (2.5%) and
      irritability (2.1%). We conclude that adjunctive PER may lead to at least
      temporary freedom of seizures in some of these highly difficult-to-treat
      patients. Adverse events are not uncommon. 

PMID- 24721199
TI  - LGI1 microdeletions are not a frequent cause of partial epilepsy with auditory
      features (PEAF).
AB  - Heterozygous mutations of the leucine-rich, glioma-inactivated 1 gene (LGI1) are
      the major known cause of partial epilepsy with auditory features (PEAF),
      accounting for roughly 50% of families. Recently, a partial gene microdeletion
      has been reported in a single family. To assess the contribution of LGI1
      microrearrangements to the pathogenesis of PEAF, we screened 50 patients negative
      for point mutations through multiplex ligation-dependent probe amplification
      (MLPA) analysis. No cryptic imbalances were found in LGI1, suggesting that LGI1
      microdeletions are not a frequent cause of PEAF. Despite the small number of
      examined patients and the need for replication studies, these findings support
      the hypothesis that diagnostic screening for LGI1 microrearrangements lacks
      clinical utility, especially for sporadic cases, and further highlight genetic
      heterogeneity of familial and sporadic PEAF. 

PMID- 24721198
TI  - Frequency-dependent amplitude alterations of resting-state spontaneous
      fluctuations in idiopathic generalized epilepsy.
AB  - PURPOSE: Amplitude of low-frequency fluctuation (ALFF) of blood-oxygenation level
      dependent (BOLD) has proven a promising way to detect disease-related local brain
      activity. However, routine approach employs an arbitrary frequency band of 0.01
      0.08 Hz, which lacks frequency specificity and blinds to the information
      contained in other frequency bands. This study investigated the amplitude of
      fluctuations in full BOLD frequency bands, and addressed how amplitudes of
      fluctuations change in each specific frequency range in idiopathic generalized
      epilepsy (IGE). METHODS: Thirty-four IGE patients with generalized tonic-clonic
      seizure and the same number of age- and sex-matched healthy controls were
      included. Functional MRI data were acquired using a 2s repetition time. Routine
      amplitude of low-frequency fluctuation analysis was first performed. The regions
      showing group difference were set as Region-of-interest for analysis of
      amplitudes of full-frequency. The amplitudes of BOLD fluctuations were
      consecutively performed at each frequency bin of 0.002 Hz, and specific frequency
      amplitude analyses were performed in five different frequency ranges (0-0.01 Hz,
      0.01-0.027 Hz, 0.027-0.073 Hz, 0.073-0.198 Hz, and 0.198-0.25 Hz). KEY FINDINGS:
      The thalamus and prefrontal cortex showed significant group differences in
      routine amplitude analysis. For amplitude of full-frequency analysis, a reverse
      pattern was found in the dynamic changes between the thalamus and prefrontal
      cortex in IGE. Moreover, the prefrontal cortex showed amplitude difference in the
      0.01-0.027 Hz band, while the thalamus showed amplitude difference in the 0.027
      0.073 Hz band. Both these two regions showed amplitude differences in 0.198-0.25
      Hz band. SIGNIFICANCE: We demonstrated the characteristic alterations of
      amplitude of BOLD fluctuations in IGE in frequency domain. The amplitude analysis
      of full frequency may potentially help to select specific frequency range for
      detecting epilepsy-related brain activity, and provide insights into the
      pathophysiological mechanism of IGE.

PMID- 24721200
TI  - Peri-ictal QTc changes are not associated with hypoxemia.
AB  - It has previously been suggested that abnormalities in cardiac repolarization
      (QTc lengthening and shortening) are more likely to accompany seizures with
      hypoxemia and may be involved in sudden unexpected death in epilepsy (SUDEP).
      Accordingly, we evaluated for associations between peri-ictal QTc changes and
      hypoxemia. We performed a reanalysis of cardiac and respiratory data gathered
      prospectively in our epilepsy monitoring units. The Bazett, Fridericia,
      Framingham, and Hodges heart rate correction formulas were utilized to calculate
      QTc in the pre-ictal, ictal, and post-ictal periods. Hypoxemia (defined as a drop
      in oxygen saturation below 90% for at least four contiguous seconds) was also
      examined during identical periods. Fifty-eight seizures from 29 patients were
      analyzed. Peri-ictal hypoxemia was not rare, occurring in 18/58 (31%) seizures.
      QTc lengthening was more commonly observed than shortening, with 11/58 (19%)
      seizures demonstrating peri-ictal QTc values>=500 using the Bazett formula. There
      was no significant difference between the minimum and maximum QTc values in
      seizures with and without peri-ictal hypoxemia, regardless of the correction
      formula utilized. All examined parameters of QTc lengthening and shortening were
      not associated with peri-ictal hypoxemia. This suggests that factors other than
      hypoxia result in peri-ictal cardiac repolarization abnormalities. 

PMID- 24721202
TI  - Drug treatment in patients with newly diagnosed unprovoked seizures/epilepsy.
AB  - PURPOSE: The objective of this study was to analyze drug treatment in patients
      with newly diagnosed unprovoked seizures/epilepsy in a population-based cohort in
      Stockholm, Sweden. METHOD: Clinical data from the Stockholm Incidence Registry of
      Epilepsy was cross-linked with drug dispensing data from the Swedish Prescribed
      Drug Register to analyze drug treatment in patients diagnosed with unprovoked
      seizures between 2006 and 2008. Specific questions addressed were the use of
      other medications at seizures onset, the proportion of patients initiated on
      different antiepileptic drugs (AEDs) within one year after inclusion, and the
      extent of switching between different AEDs during the first year. RESULTS: In
      total 367 patients were included. More than 50% had other medications prescribed
      at date of first seizure. All together, 262 patients received an AED within one
      year and 257 patients (98%) were initiated on monotherapy. One year after first
      prescription, 147 patients (56%) remained on the initially prescribed AED and 48
      patients (18%) had switched to another AED. Among the remaining patients, 29
      (11%) had died and 38 patients (15%) had discontinued AED treatment. CONCLUSIONS:
      A majority of all patients with epilepsy receive treatment within one year. Many
      patients use other medications and several of them are related to known
      comorbidities and can also be involved in drug-drug interactions. Nevertheless,
      most patients remained on the same AED at the end of the first year.

PMID- 24721201
TI  - Serial postoperative awake and sleep EEG and long-term seizure outcome after
      anterior temporal lobectomy for hippocampal sclerosis.
AB  - OBJECTIVE: To test if postoperative prolonged awake and sleep EEG monitoring
      predict long-term seizure outcome in patients operated for drug-resistant
      temporal lobe epilepsy due to hippocampal sclerosis (TLE-HS). METHODS: This
      longitudinal study includes 107 patients with MTLE-HS who underwent anterior
      temporal lobectomy (ATL), were followed for at least 5 years (mean 8.3, range 5
      12), had postoperative EEG after 2 months and at least one prolonged video-EEG
      monitoring during both wakefulness and sleep after 12 and 24 months. At each
      follow-up visit, the presence of interictal epileptiform discharges (IED) was
      determined, and seizure outcome was evaluated. RESULTS: Sixty-six patients (62%)
      remained free from auras and seizures throughout the follow-up period. Twenty-six
      (24%), 22 (21%), and 16 (16%) patients had IED at the 2-month, 12-month, and 24
      month follow-up, respectively. The presence of IED at each time point was found
      to be associated with seizure or aura recurrence. Sleep recording contributed to
      the identification of patients with IED, as half of patients with IED displayed
      anomalies in sleep EEG only. In multivariate analysis, the presence of IED 2
      months after surgery was found to be associated with seizure or aura recurrence
      independent of pre-operative factors consistently reported as outcome predictors
      in the literature. CONCLUSIONS: The presence of IED in serial postoperative EEG
      including sleep recording may predict long-term seizure outcome after ATL for TLE
      HS. Serial postoperative EEGs may contribute to outcome prediction and help
      making decision about medication withdrawal in patients operated for TLE-HS.

PMID- 24721203
TI  - Validated HILIC-MS/MS assay for determination of vindesine in human plasma:
      Application to a population pharmacokinetic study.
AB  - The first HILIC-tandem mass spectrometry (MS/MS) method for determination of
      vindesine (VDS) in human plasma using vinorelbine as an internal standard (IS)
      has been developed and validated. Plasma samples clean-up consisted of solid
      phase extraction with a strataTM-X column. The compounds were separated on a
      HILIC column with an isocratic mobile phase consisting of acetonitrile and 15mM
      ammonium acetate buffer containing 0.15% formic acid (80:20, v/v). The detection
      was performed on a triple quadrupole tandem mass spectrometer via electrospray
      positive ionization (ESI(+)). The ion transitions recorded in multiple reaction
      monitoring mode were m/z 754.6->123.8 for VDS and 779.4->323.3 for IS,
      respectively. Linear calibration curves were obtained in the concentration range
      of 0.3-28ng/ml and the lower limit of quantification for VDS was 0.3ng/ml. The
      coefficient of variation of the assay precision was less than 13%, and the
      accuracy exceeded 96%. The developed assay method was successfully applied for
      the evaluation of population pharmacokinetics of VDS after intravenous infusion
      of Xi Ai Ke Vial((r)) (3mg of Vindesine Sulfate for Injection) to Chinese Han
      subjects with hematological malignant disorders. 

PMID- 24721204
TI  - Determination of residual acetone and acetone related impurities in drug product
      intermediates prepared as Spray Dried Dispersions (SDD) using gas chromatography
      with headspace autosampling (GCHS).
AB  - Spray Dried Dispersions (SDD) are uniform mixtures of a specific ratio of
      amorphous active pharmaceutical ingredient (API) and polymer prepared via a spray
      drying process. Volatile solvents are employed during spray drying to facilitate
      the formation of the SDD material. Following manufacture, analytical methodology
      is required to determine residual levels of the spray drying solvent and its
      associated impurities. Due to the high level of polymer in the SDD samples,
      direct liquid injection with Gas Chromatography (GC) is not a viable option for
      analysis. This work describes the development and validation of an analytical
      approach to determine residual levels of acetone and acetone related impurities,
      mesityl oxide (MO) and diacetone alcohol (DAA), in drug product intermediates
      prepared as SDDs using GC with headspace (HS) autosampling. The method
      development for these analytes presented a number of analytical challenges which
      had to be overcome before the levels of the volatiles of interest could be
      accurately quantified. GCHS could be used after two critical factors were
      implemented; (1) calculation and application of conversion factors to 'correct'
      for the reactions occurring between acetone, MO and DAA during generation of the
      headspace volume for analysis, and the addition of an equivalent amount of
      polymer into all reference solutions used for quantitation to ensure
      comparability between the headspace volumes generated for both samples and
      external standards. This work describes the method development and optimisation
      of the standard preparation, the headspace autosampler operating parameters and
      the chromatographic conditions, together with a summary of the validation of the
      methodology. The approach has been demonstrated to be robust and suitable to
      accurately determine levels of acetone, MO and DAA in SDD materials over the
      linear concentration range 0.008-0.4MUL/mL, with minimum quantitation limits of
      20ppm for acetone and MO, and 80ppm for DAA. 

PMID- 24721205
TI  - Wolbachia-induced paternal defect in Drosophila is likely by interaction with the
      juvenile hormone pathway.
AB  - Wolbachia are endosymbionts that infect many insect species. They can manipulate
      the host's reproduction to increase their own maternal transmission. Cytoplasmic
      incompatibility (CI) is one such manipulation, which is expressed as embryonic
      lethality when Wolbachia-infected males mate with uninfected females. However,
      matings between males and females carrying the same Wolbachia strain result in
      viable progeny. The molecular mechanisms of CI are currently not clear. We have
      previously reported that the gene Juvenile hormone-inducible protein 26 (JhI-26)
      exhibited the highest upregulation in the 3rd instar larval testes of Drosophila
      melanogaster when infected by Wolbachia. This is reminiscent of an interaction
      between Wolbachia and juvenile hormone (JH) pathway in flies. Considering that
      Jhamt gene encodes JH acid methyltransferase, a key regulatory enzyme of JH
      biosynthesis, and that methoprene-tolerant (Met) has been regarded as the best JH
      receptor candidate, we first compared the expression of Jhamt and Met between
      Wolbachia-infected and uninfected fly testes to investigate whether Wolbachia
      infection influence the JH signaling pathway. We found that the expressions of
      Jhamt and Met were significantly increased in the presence of Wolbachia,
      suggesting an interaction of Wolbachia with the JH signaling pathway. Then, we
      found that overexpression of JhI-26 in Wolbachia-free transgenic male flies
      caused paternal-effect lethality that mimics the defects associated with CI. JhI
      26 overexpressing males resulted in significantly decrease in hatch rate.
      Surprisingly, Wolbachia-infected females could rescue the egg hatch. In addition,
      we showed that overexpression of JhI-26 caused upregulation of the male accessory
      gland protein (Acp) gene CG10433, but not vice versa. This result suggests that
      JhI-26 may function at the upstream of CG10433. Likewise, overexpression of
      CG10433 also resulted in paternal-effect lethality. Both JhI-26 and CG10433
      overexpressing males resulted in nuclear division defects in the early embryos.
      Finally, we found that Wolbachia-infected males decreased the propensity of the
      mated females to remating, a phenotype also caused by both JhI-26 and CG10433
      overexpressing males. Taken together, our results provide a working hypothesis
      whereby Wolbachia induce paternal defects in Drosophila probably by interaction
      with the JH pathway via JH response genes JhI-26 and CG10433. 

PMID- 24721206
TI  - The impact of the 1918 Spanish flu epidemic on economic performance in Sweden: an
      investigation into the consequences of an extraordinary mortality shock.
AB  - We study the impact of the 1918 influenza pandemic on short- and medium-term
      economic performance in Sweden. The pandemic was one of the severest and
      deadliest pandemics in human history, but it has hitherto received only scant
      attention in the economic literature--despite representing an unparalleled labour
      supply shock. In this paper, we exploit seemingly exogenous variation in
      incidence rates between Swedish regions to estimate the impact of the pandemic.
      The pandemic led to a significant increase in poorhouse rates. There is also
      evidence that capital returns were negatively affected by the pandemic. However,
      contrary to predictions, we find no discernible effect on earnings.

PMID- 24721207
TI  - Mycobacterium tuberculosis pili (MTP), a putative biomarker for a tuberculosis
      diagnostic test.
AB  - Novel biomarkers are urgently needed for point of care TB diagnostics. In this
      study, we investigated the potential of the pilin subunit protein encoded by the
      mtp gene as a diagnostic biomarker. BLAST analysis of the mtp gene on published
      genome databases, and amplicon sequencing were performed in Mycobacterium
      tuberculosis Complex (MTBC) strains and other organisms. The protein secondary
      structure of the amino acid sequences of non-tuberculous Mycobacteria that
      partially aligned with the mtp sequence was analysed with PredictProtein
      software. The mtp gene and corresponding amino acid sequence of MTBC were 100%
      homologous with H37Rv, in contrast to the partial alignment of the non
      tuberculous Mycobacteria. The mtp gene was present in all 91 clinical isolates of
      MTBC. Except for 2 strains with point mutations, the sequence was 100% conserved
      among the clinical strains. The mtp gene could not be amplified in all non
      tuberculous Mycobacteria and respiratory organisms. The predicted MTP protein
      structure of Mycobacterium avium, Mycobacterium ulcerans and Mycobacterium
      abscessus differed significantly from that of the M. tuberculosis, which was
      similar to Mycobacterium marinum. The absence of the mtp gene in non-tuberculous
      Mycobacteria and other respiratory bacteria suggests that its encoded product,
      the pilin subunit protein of M. tuberculosis may be a suitable marker for a point
      of care TB test. 

PMID- 24721208
TI  - Fusions involving protein kinase C and membrane-associated proteins in benign
      fibrous histiocytoma.
AB  - Benign fibrous histiocytoma (BFH) is a mesenchymal tumor that most often occurs
      in the skin (so-called dermatofibroma), but may also appear in soft tissues (so
      called deep BFH) and in the skeleton (so-called non-ossifying fibroma). The
      origin of BFH is unknown, and it has been questioned whether it is a true
      neoplasm. Chromosome banding, fluorescence in situ hybridization, single
      nucleotide polymorphism arrays, RNA sequencing, RT-PCR and quantitative real-time
      PCR were used to search for recurrent somatic mutations in a series of BFH. BFHs
      were found to harbor recurrent fusions of genes encoding membrane-associated
      proteins (podoplanin, CD63 and LAMTOR1) with genes encoding protein kinase C
      (PKC) isoforms PRKCB and PRKCD. PKCs are serine-threonine kinases that through
      their many phosphorylation targets are implicated in a variety of cellular
      processes, as well as tumor development. When inactive, the amino-terminal,
      regulatory domain of PKCs suppresses the activity of their catalytic domain. Upon
      activation, which requires several steps, they typically translocate to cell
      membranes, where they interact with different signaling pathways. The detected
      PDPN-PRKCB, CD63-PRKCD and LAMTOR1-PRKCD gene fusions are all predicted to result
      in chimeric proteins consisting of the membrane-binding part of PDPN, CD63 or
      LAMTOR1 and the entire catalytic domain of the PKC. This novel pathogenetic
      mechanism should result in constitutive kinase activity at an ectopic location.
      The results show that BFH indeed is a true neoplasm, and that distorted PKC
      activity is essential for tumorigenesis. The findings also provide means to
      differentiate BFH from other skin and soft tissue tumors. This article is part of
      a Directed Issue entitled: Rare cancers. 

PMID- 24721209
TI  - 2-Arachidonoylglycerol modulates human endothelial cell/leukocyte interactions by
      controlling selectin expression through CB1 and CB2 receptors.
AB  - Accumulated evidence points to a key role for endocannabinoids in cell migration,
      and here we sought to characterize the role of these substances in early events
      that modulate communication between endothelial cells and leukocytes. We found
      that 2-arachidonoylglycerol (2-AG) was able to initiate and complete the
      leukocyte adhesion cascade, by modulating the expression of selectins. A short
      exposure of primary human umbilical vein endothelial cells (HUVECs) to 2-AG was
      sufficient to prime them towards an activated state: within 1h of treatment,
      endothelial cells showed time-dependent plasma membrane expression of P- and E
      selectins, which both trigger the initial steps (i.e., capture and rolling) of
      leukocyte adhesion. The effect of 2-AG was mediated by CB1 and CB2 receptors and
      was long lasting, because endothelial cells incubated with 2-AG for 1h released
      the pro-inflammatory cytokine tumour necrosis factor-alpha (TNF-alpha) for up to
      24h. Consistently, TNF-alpha-containing medium was able to promote leukocyte
      recruitment: human Jurkat T cells grown in conditioned medium derived from 2-AG
      treated HUVECs showed enhanced L-selectin and P-selectin glycoprotein ligand-1
      (PSGL1) expression, as well as increased efficiency of adhesion and trans
      migration. In conclusion, our in vitro data indicate that 2-AG, by acting on
      endothelial cells, might indirectly promote leukocyte recruitment, thus
      representing a potential therapeutic target for treatment of diseases where
      impaired endothelium/leukocyte interactions take place. 

PMID- 24721210
TI  - HDAC inhibitors induce apoptosis but not cellular senescence in Gadd45alpha
      deficient E1A+Ras cells.
AB  - HDAC inhibitors (HDIs) induce irreversible cell cycle arrest and senescence in
      E1A+Ras expressing cells. Furthermore, HDIs activate Gadd45alpha/NF-kappaB
      signaling pathway to suppress apoptosis thereby promoting the cell survival.
      Here, to clarify the role of Gadd45alpha in realization of the antiapoptotic
      program, we compared wild-type E1A+Ras cells and the cells with knockout of
      gadd45alpha gene (Gadd45alpha-/- cells). As in Gadd45alpha-expressing E1A+Ras
      cells, HDIs induce irreversible cell cycle arrest in Gadd45alpha-/- cells, but
      the arrested cells do not senesce and eventually die due to activation of the
      apoptotic death program. These data suggest that the expression of Gadd45alpha is
      involved in maintaining the balance of pro- and anti-apoptotic stimuli, while
      lack or loss of Gadd45 directs the cells to apoptosis after HDIs treatment.
      Appropriately Gadd45alpha-deficient cells demonstrate a higher level of pro
      apoptotic signals, whereas the anti-apoptotic program is suppressed. The elevated
      apoptotic background of Gadd45alpha-/- cells is accompanied by higher levels of
      Ser15-phosphorylated p53 and p21/Waf1 proteins that additionally commit the cells
      to HDIs-induced apoptosis. Additionally, loss of Gadd45alpha protein activates
      the DDR signaling pathway as demonstrated by nuclear pATM staining, accumulation
      of gammaH2AX foci and an increase of single-strand DNA breaks. Thus, in wild-type
      E1A+Ras cells the p53-dependent expression of Gadd45alpha is necessary not only
      for DNA repair and HDI-induced cellular senescence, but also to withstand to
      apoptosis after DNA damage and stress. Therefore the use of HDIs in combination
      with agents that block Gadd45alpha function may have promise for cancer therapy. 

PMID- 24721212
TI  - Effect of glutamine substitution by TCA cycle intermediates on the production and
      sialylation of Fc-fusion protein in Chinese hamster ovary cell culture.
AB  - In an effort to reduce the accumulation of ammonia in culture medium, three
      different TCA cycle intermediates, (alpha-ketoglutarate (alpha-KG), citric acid
      and succinic acid) along with glutamic acid for a comparison, were examined as a
      substitute for glutamine with rCHO cell line producing a Fc-fusion glycoprotein.
      Among them, alpha-KG showed the best production performance. When cells were
      cultivated with 4 mM alpha-KG, the final ammonia concentration did not exceed 3
      mM, which is less than one fourth of that with 4 mM glutamine. The replacement of
      glutamine increased the lag phase and reduced cell growth. However, it increased
      the specific productivity by 2.7-fold, resulting in a 1.3-fold increase in the
      maximum product concentration. Furthermore, the sialic acid content of the Fc
      fusion protein with 4 mM alpha-KG was higher than that with 4 mM glutamine in all
      cultures, most likely due to the lower ammonia concentration. The results of
      Western blotting and activity assays of intracellular alpha-2,3-sialyltransferase
      and extracellular sialidases are in good agreement with tests done to assess the
      sialic acid content of the Fc-fusion protein. Taken together, the data obtained
      here demonstrate that alpha-KG is a potential substitute for glutamine for
      improved glycoprotein production in rCHO cells.

PMID- 24721211
TI  - Characterization of new bacterial catabolic genes and mobile genetic elements by
      high throughput genetic screening of a soil metagenomic library.
AB  - A mix of oligonucleotide probes was used to hybridize soil metagenomic DNA from a
      fosmid clone library spotted on high density membranes. The pooled radio-labeled
      probes were designed to target genes encoding glycoside hydrolases GH18,
      dehalogenases, bacterial laccases and mobile genetic elements (integrases from
      integrons and insertion sequences). Positive hybridizing spots were affiliated to
      the corresponding clones in the library and the metagenomic inserts were
      sequenced. After assembly and annotation, new coding DNA sequences related to
      genes of interest were identified with low protein similarity against the closest
      hits in databases. This work highlights the sensitivity of DNA/DNA hybridization
      techniques as an effective and complementary way to recover novel genes from
      large metagenomic clone libraries. This study also supports that some of the
      identified catabolic genes might be associated with horizontal transfer events. 

PMID- 24721213
TI  - Quantification of methanogenic heterodisulfide reductase activity in biogas
      sludge.
AB  - Methanogenic archaea are essential for the production of methane in biogas
      plants. Here we present enzymatic test systems for the analysis of the metabolic
      activity of methanogens based on the heterodisulfide reductase reaction. The
      first rapid test shows that heterodisulfide reductase can be detected in 1 g of
      biogas sludge after sonication and centrifugation. The resulting cell lysate used
      reduced methylviologen for heterodisulfide reduction, a reaction that is
      specifically catalyzed by methanogenic heterodisulfide reductase. In the second
      test cell lysate from 60 g of biogas sludge was separated by ultracentrifugation.
      Both, cytoplasmic membrane and cytoplasmic fractions revealed heterodisulfide
      reductase activity, indicating the presence of hydrogenotrophic and aceticlastic
      methanogens, respectively.

PMID- 24721214
TI  - Broad metabolic sensitivity profiling of a prototrophic yeast deletion
      collection.
AB  - BACKGROUND: Genome-wide sensitivity screens in yeast have been immensely popular
      following the construction of a collection of deletion mutants of non-essential
      genes. However, the auxotrophic markers in this collection preclude experiments
      on minimal growth medium, one of the most informative metabolic environments.
      Here we present quantitative growth analysis for mutants in all 4,772 non
      essential genes from our prototrophic deletion collection across a large set of
      metabolic conditions. RESULTS: The complete collection was grown in environments
      consisting of one of four possible carbon sources paired with one of seven
      nitrogen sources, for a total of 28 different well-defined metabolic
      environments. The relative contributions to mutants' fitness of each carbon and
      nitrogen source were determined using multivariate statistical methods. The
      mutant profiling recovered known and novel genes specific to the processing of
      nutrients and accurately predicted functional relationships, especially for
      metabolic functions. A benchmark of genome-scale metabolic network modeling is
      also given to demonstrate the level of agreement between current in silico
      predictions and hitherto unavailable experimental data. CONCLUSIONS: These data
      address a fundamental deficiency in our understanding of the model eukaryote
      Saccharomyces cerevisiae and its response to the most basic of environments.
      While choice of carbon source has the greatest impact on cell growth, specific
      effects due to nitrogen source and interactions between the nutrients are
      frequent. We demonstrate utility in characterizing genes of unknown function and
      illustrate how these data can be integrated with other whole-genome screens to
      interpret similarities between seemingly diverse perturbation types.

PMID- 24721215
TI  - Assessing the impact of health literacy on education retention of stroke
      patients.
AB  - INTRODUCTION: Inadequate health literacy is a pervasive problem with major
      implications for reduced health status and health disparities. Despite the role
      of focused education in both primary and secondary prevention of stroke, the
      effect of health literacy on stroke education retention has not been reported. We
      examined the relationship of health literacy to the retention of knowledge after
      recommended stroke education. METHODS: This prospective cross-sectional study was
      conducted at an urban safety-net hospital. Study subjects were patients older
      than 18 admitted to the hospital stroke unit with a diagnosis of acute ischemic
      stroke who were able to provide informed consent to participate (N = 100). Health
      literacy levels were measured by using the short form of Test of Functional
      Health Literacy in Adults. Patient education was provided to patients at an
      inpatient stroke unit by using standardized protocols, in compliance with Joint
      Commission specifications. The education outcomes for poststroke care education,
      knowledge retention, was assessed for each subject. The effect of health literacy
      on the Stroke Patient Education Retention scores was assessed by using univariate
      and multivariate analyses. RESULTS: Of the 100 participating patients, 59% had
      inadequate to marginal health literacy. Stroke patients who had marginal health
      literacy (mean score, 7.45; standard deviation [SD], 1.9) or adequate health
      literacy (mean score, 7.31; SD, 1.76) had statistically higher education outcome
      scores than those identified as having inadequate health literacy (mean score,
      5.58; SD, 2.06). Results from multivariate analysis indicated that adequate
      health literacy was most predictive of education outcome retention. CONCLUSIONS:
      This study demonstrated a clear relationship between health literacy and stroke
      education outcomes. Studies are needed to better understand the relationship of
      health literacy to key educational outcomes for primary or secondary prevention
      of stroke and to refine stroke education for literacy levels of high-risk
      populations.

PMID- 24721216
TI  - Comparison of fecal occult blood tests for colorectal cancer screening in an
      Alaska Native population with high prevalence of Helicobacter pylori infection,
      2008-2012.
AB  - INTRODUCTION: Alaska Native colorectal cancer (CRC) incidence and mortality rates
      are the highest of any ethnic/racial group in the United States. CRC screening
      using guaiac-based fecal occult blood tests (gFOBT) are not recommended for
      Alaska Native people because of false-positive results associated with a high
      prevalence of Helicobacter pylori-associated hemorrhagic gastritis. This study
      evaluated whether the newer immunochemical FOBT (iFOBT) resulted in a lower false
      positive rate and higher specificity for detecting advanced colorectal neoplasia
      than gFOBT in a population with elevated prevalence of H. pylori infection.
      METHODS: We used a population-based sample of 304 asymptomatic Alaska Native
      adults aged 40 years or older undergoing screening or surveillance colonoscopy
      (April 2008-January 2012). RESULTS: Specificity differed significantly (P < .001)
      between gFOBT (76%; 95% CI, 71%-81%) and iFOBT (92%; 95% CI, 89%-96%). Among H.
      pylori-positive participants (54%), specificity of iFOBT was even higher (93% vs
      69%). Overall, sensitivity did not differ significantly (P = .73) between gFOBT
      (29%) and iFOBT (36%). Positive predictive value was 11% for gFOBT and 32% for
      iFOBT. CONCLUSION: The iFOBT had a significantly higher specificity than gFOBT,
      especially in participants with current H. pylori infection. The iFOBT represents
      a potential strategy for expanding CRC screening among Alaska Native and other
      populations with elevated prevalence of H. pylori, especially where access to
      screening endoscopy is limited.

PMID- 24721217
TI  - Testing the effectiveness of an abbreviated version of the Nutrition Detectives
      program.
AB  - INTRODUCTION: Obese or overweight children have an increased risk for chronic
      diseases. Targeting diet and exercise in schools could help prevent childhood
      obesity. We have previously shown the effectiveness of a 90-minute nutrition
      program in improving elementary school students' food-label literacy. The
      objective of this study was to investigate the effectiveness of a 45-minute
      version of the program. METHODS: We conducted a pre-post study in a public school
      district, with no control group. We provided teacher training and program
      materials. Participants were 5th-grade students in 5 schools who had parental
      consent and were willing to take part. We condensed the program to a 45-minute
      lesson with a presentation and hands-on activity. The lesson showed students why
      and how to make healthful food choices based on Nutrition Facts panels and
      ingredient lists. The district's physical education teachers taught the lesson.
      The primary outcome measure was food-label literacy (ie, the ability to
      distinguish between more and less healthful foods using a validated test
      instrument with Nutrition Facts panels and ingredient lists). RESULTS: A total of
      212 students completed pre-post measures. Following program delivery, we observed
      a significant gain of 16.2 percentage points in scores overall, ranging from 4.3
      percentage points to 23.6 percentage points among schools. Results were similar
      to those achieved with the 90-minute program. DISCUSSION: The condensed nutrition
      program improved students' food-label literacy while requiring a minimal
      allocation of time. Further studies in other school districts would be useful.

PMID- 24721218
TI  - Cardiovascular disease risk among the Mexican American population in the Texas
      Mexico border region, by age and length of residence in United States.
AB  - INTRODUCTION: Although the relationship between health behaviors and outcomes
      such as smoking and obesity with longer residence in the United States among
      Mexican American immigrants is established, the relationship between length of
      residency in the United States and risk for cardiovascular disease (CVD) is not
      fully understood. The objective of this study was to determine the relationship
      between immigrant status, length of residence in the United States, age, and CVD
      markers in a sample of Mexican American adults living in Brownsville, Texas.
      METHODS: We categorized participants in the Cameron County Hispanic Cohort study
      as immigrants in the United States for 10 years or less, immigrants in the United
      States for more than 10 years, or born in the United States. We conducted
      logistic and ordinary least squares regression for self-reported chronic
      conditions and CVD biomarkers. RESULTS: We found bivariate differences in the
      prevalence of self-reported conditions and 1 CVD biomarker (low-density
      lipoprotein cholesterol) by length of residence in the middle (41-64 y) and
      younger (18-40 y) age groups. After adjusting for covariates, the following
      varied significantly by immigrant status: stroke and high cholesterol (self
      reported conditions) and diastolic blood pressure, systolic blood pressure, total
      cholesterol, and low-density lipoprotein cholesterol (CVD biomarkers).
      CONCLUSION: The association between immigrant status, length of residence in the
      United States, and CVD markers varied. The effect of length of residence in the
      United States or immigrant status may depend on age and may be most influential
      in middle or older age.

PMID- 24721219
TI  - Anxiety and depression related to elevated dopamine in a patient with multiple
      mediastinal paragangliomas.
AB  - Paragangliomas are rare neuroendocrine tumors. Occasionally they secrete
      catecholamines in sufficient quantities to cause symptoms. These may include
      psychiatric symptoms such as anxiety and depression. We describe a patient with
      multiple mediastinal paragangliomas and persistently elevated dopamine levels who
      presented with anxiety and depression. She later went on to develop paranoid
      schizophrenia, which we feel was coincidental. This case illustrates anxiety and
      depressive symptoms associated with elevated dopamine and the importance of
      awareness of psychiatric manifestations of neuroendocrine tumors among
      psychiatrists and physicians.

PMID- 24721220
TI  - Guidelines and Straitjackets: blood pressure targets in the era of the Eighth
      Joint National Committee.

PMID- 24721221
TI  - Resistant hypertension in obstructive sleep apnea: is continuous positive airway
      pressure the next step?

PMID- 24721223
TI  - Discrete-time online learning control for a class of unknown nonaffine nonlinear
      systems using reinforcement learning.
AB  - In this paper, a reinforcement-learning-based direct adaptive control is
      developed to deliver a desired tracking performance for a class of discrete-time
      (DT) nonlinear systems with unknown bounded disturbances. We investigate multi
      input-multi-output unknown nonaffine nonlinear DT systems and employ two neural
      networks (NNs). By using Implicit Function Theorem, an action NN is used to
      generate the control signal and it is also designed to cancel the nonlinearity of
      unknown DT systems, for purpose of utilizing feedback linearization methods. On
      the other hand, a critic NN is applied to estimate the cost function, which
      satisfies the recursive equations derived from heuristic dynamic programming. The
      weights of both the action NN and the critic NN are directly updated online
      instead of offline training. By utilizing Lyapunov's direct method, the closed
      loop tracking errors and the NN estimated weights are demonstrated to be
      uniformly ultimately bounded. Two numerical examples are provided to show the
      effectiveness of the present approach. 

PMID- 24721222
TI  - Platelet adhesion to polyurethane urea under pulsatile flow conditions.
AB  - Platelet adhesion to a polyurethane urea surface is a precursor to thrombus
      formation within blood-contacting cardiovascular devices, and platelets have been
      found to adhere strongly to polyurethane surfaces below a shear rate of
      approximately 500 s(-1). The aim of the current work is to determine the
      properties of platelet adhesion to the polyurethane urea surface as a function of
      time-varying shear exposure. A rotating disk system was used to study the
      influence of steady and pulsatile flow conditions (e.g., cardiac inflow and
      sawtooth waveforms) for platelet adhesion to the biomaterial surface. All
      experiments were conducted with the same root mean square angular rotation
      velocity (29.63 rad/s) and waveform period. The disk was rotated in platelet-rich
      bovine plasma for 2 h, with adhesion quantified by confocal microscopy
      measurements of immunofluorescently labeled bovine platelets. Platelet adhesion
      under pulsating flow was found to decay exponentially with increasing shear rate.
      Adhesion levels were found to depend upon peak platelet flux and shear rate,
      regardless of rotational waveform. In combination with flow measurements, these
      results may be useful for predicting regions susceptible to thrombus formation
      within ventricular assist devices.

PMID- 24721224
TI  - Towards limb position invariant myoelectric pattern recognition using time
      dependent spectral features.
AB  - Recent studies in Electromyogram (EMG) pattern recognition reveal a gap between
      research findings and a viable clinical implementation of myoelectric control
      strategies. One of the important factors contributing to the limited performance
      of such controllers in practice is the variation in the limb position associated
      with normal use as it results in different EMG patterns for the same movements
      when carried out at different positions. However, the end goal of the myoelectric
      control scheme is to allow amputees to control their prosthetics in an intuitive
      and accurate manner regardless of the limb position at which the movement is
      initiated. In an attempt to reduce the impact of limb position on EMG pattern
      recognition, this paper proposes a new feature extraction method that extracts a
      set of power spectrum characteristics directly from the time-domain. The end goal
      is to form a set of features invariant to limb position. Specifically, the
      proposed method estimates the spectral moments, spectral sparsity, spectral flux,
      irregularity factor, and signals power spectrum correlation. This is achieved
      through using Fourier transform properties to form invariants to amplification,
      translation and signal scaling, providing an efficient and accurate
      representation of the underlying EMG activity. Additionally, due to the inherent
      temporal structure of the EMG signal, the proposed method is applied on the
      global segments of EMG data as well as the sliced segments using multiple
      overlapped windows. The performance of the proposed features is tested on EMG
      data collected from eleven subjects, while implementing eight classes of
      movements, each at five different limb positions. Practical results indicate that
      the proposed feature set can achieve significant reduction in classification
      error rates, in comparison to other methods, with ~8% error on average across all
      subjects and limb positions. A real-time implementation and demonstration is also
      provided and made available as a video supplement (see Appendix A). 

PMID- 24721225
TI  - X-exome sequencing in Finnish families with intellectual disability--four novel
      mutations and two novel syndromic phenotypes.
AB  - BACKGROUND: X-linked intellectual disability (XLID) is a group of genetically
      heterogeneous disorders characterized by substantial impairment in cognitive
      abilities, social and behavioral adaptive skills. Next generation sequencing
      technologies have become a powerful approach for identifying molecular gene
      mutations relevant for diagnosis. METHODS & OBJECTIVES: Enrichment of X
      chromosome specific exons and massively parallel sequencing was performed for
      identifying the causative mutations in 14 Finnish families, each of them having
      several males affected with intellectual disability of unknown cause. RESULTS: We
      found four novel mutations in known XLID genes. Two mutations; one previously
      reported missense mutation (c.1111C > T), and one novel frameshift mutation (c.
      990_991insGCTGC) were identified in SLC16A2, a gene that has been linked to Allan
      Herndon-Dudley syndrome (AHDS). One novel missense mutation (c.1888G > C) was
      found in GRIA3 and two novel splice donor site mutations (c.357 + 1G > C and
      c.985 + 1G > C) were identified in the DLG3 gene. One missense mutation (c.1321C
      > T) was identified in the candidate gene ZMYM3 in three affected males with a
      previously unrecognized syndrome characterized by unique facial features, aortic
      stenosis and hypospadia was detected. All of the identified mutations segregated
      in the corresponding families and were absent in > 100 Finnish controls and in
      the publicly available databases. In addition, a previously reported benign
      variant (c.877G > A) in SYP was identified in a large family with nine affected
      males in three generations, who have a syndromic phenotype. CONCLUSIONS: All of
      the mutations found in this study are being reported for the first time in
      Finnish families with several affected male patients whose etiological diagnoses
      have remained unknown to us, in some families, for more than 30 years. This study
      illustrates the impact of X-exome sequencing to identify rare gene mutations and
      the challenges of interpreting the results. Further functional studies are
      required to confirm the cause of the syndromic phenotypes associated with ZMYM3
      and SYP in this study.

PMID- 24721226
TI  - Bruton's tyrosine kinase inhibitors for the treatment of rheumatoid arthritis.
AB  - The function and role of Bruton's tyrosine kinase (BTK) in human B cell
      development was demonstrated by its association with X-linked agammaglobulinemia
      (XLA) manifested by a substantial reduction in immunoglobulins and B cells. BTK
      has a crucial role in pre-B cell receptor (BCR) and BCR signaling during normal B
      cell development and activation. Aberrant BCR signaling is associated with
      autoimmune diseases, such as rheumatoid arthritis (RA). In addition, BTK is also
      expressed in myeloid cell populations, including monocytes, macrophages,
      neutrophils and mast cells. These innate cells infiltrate the synovial cavity and
      produce inflammatory cytokines, aggravating arthritic symptoms. In myeloid cell
      populations, BTK functions downstream of the Fcgamma receptors (FcgammaR) and FcE
      receptors (FcER). In the absence of BTK, FcR-mediated functions, such as cytokine
      production, are impaired. In addition, Xid mice, which have a mutation in BTK,
      have decreased susceptibility to developing collagen-induced arthritis (CIA).
      Given that BTK is involved in multiple signaling pathways downstream of the BCR
      and FcR, it is an attractive therapeutic target for RA.

PMID- 24721227
TI  - Detection of Plasmodium vivax and Plasmodium falciparum DNA in human saliva and
      urine: loop-mediated isothermal amplification for malaria diagnosis.
AB  - This study investigated loop-mediated isothermal amplification (LAMP) detection
      of Plasmodium falciparum and Plasmodium vivax in urine and saliva of malaria
      patients. From May to November 2011, 108 febrile patients referred to health
      centers in Sistan and Baluchestan Province of south-eastern Iran participated in
      the study. Saliva, urine, and blood samples were analyzed with nested PCR and
      LAMP targeting the species-specific nucleotide sequence of small subunit
      ribosomal RNA gene (18S rRNA) of P. falciparum and P. vivax and evaluated for
      diagnostic accuracy by comparison to blood nested PCR assay. When nested PCR of
      blood is used as standard, microscopy and nested PCR of saliva and urine samples
      showed sensitivity of 97.2%, 89.4% and 71% and specificity of 100%, 97.3% and
      100%, respectively. LAMP sensitivity of blood, saliva, and urine was 95.8%, 47%
      and 29%, respectively, whereas LAMP specificity of these samples was 100%.
      Microscopy and nested PCR of saliva and LAMP of blood were comparable to nested
      PCR of blood (k=0.95, 0.83, and 0.94, respectively), but agreement for nested PCR
      of urine was moderate (k=0.64) and poor to fair for saliva LAMP and urine LAMP
      (k=0.38 and 0.23, respectively). LAMP assay showed low sensitivity for detection
      of Plasmodium DNA in human saliva and urine compared to results with blood and to
      nested PCR of blood, saliva, and urine. However, considering the advantages of
      LAMP technology and of saliva and urine sampling, further research into the
      method is worthwhile. LAMP protocol and precise preparation protocols need to be
      defined and optimized for template DNA of saliva and urine. 

PMID- 24721228
TI  - Is current evidence about intraoperative partial breast irradiation sufficient
      for broad implementation in clinical practice?

PMID- 24721229
TI  - Bordetella holmesii: an under-recognised Bordetella species.
AB  - Bordetella holmesii, first described in 1995, is believed to cause both invasive
      infections (bacteraemia, meningitis, endocarditis, pericarditis, pneumonia, and
      arthritis) and pertussis-like symptoms. Infection with B holmesii is frequently
      misidentified as being with B pertussis, the cause of whooping cough, because
      routine diagnostic tests for pertussis are not species-specific. In this Review,
      we summarise knowledge about B holmesii diagnosis and treatment, and assess
      research needs. Although no fatal cases of B holmesii have been reported,
      associated invasive infections can cause substantial morbidities, even in
      previously healthy individuals. Antimicrobial treatment can be problematic
      because B holmesii's susceptibility to macrolides (used empirically to treat B
      pertussis) and third-generation cephalosporins (often used to treat invasive
      infections) is lower than would be expected. B holmesii's adaptation to human
      beings is continuing, and virulence might increase, causing the need for better
      diagnostic assays and epidemiological surveillance. 

PMID- 24721230
TI  - Ensuring privacy in the study of pathogen genetics.
AB  - Rapid growth in the genetic sequencing of pathogens in recent years has led to
      the creation of large sequence databases. This aggregated sequence data can be
      very useful for tracking and predicting epidemics of infectious diseases.
      However, the balance between the potential public health benefit and the risk to
      personal privacy for individuals whose genetic data (personal or pathogen) are
      included in such work has been difficult to delineate, because neither the true
      benefit nor the actual risk to participants has been adequately defined. Existing
      approaches to minimise the risk of privacy loss to participants are based on de
      identification of data by removal of a predefined set of identifiers. These
      approaches neither guarantee privacy nor protect the usefulness of the data. We
      propose a new approach to privacy protection that will quantify the risk to
      participants, while still maximising the usefulness of the data to researchers.
      This emerging standard in privacy protection and disclosure control, which is
      known as differential privacy, uses a process-driven rather than data-centred
      approach to protecting privacy.

PMID- 24721231
TI  - Species-level assessment of the molecular basis of fluoroquinolone resistance
      among viridans group streptococci causing bacteraemia in cancer patients.
AB  - Viridans group streptococci (VGS) are a major cause of bacteraemia in neutropenic
      cancer patients, particularly those receiving fluoroquinolone prophylaxis. In
      this study, we sought to understand the molecular basis for fluoroquinolone
      resistance in VGS causing bacteraemia in cancer patients by assigning 115 VGS
      bloodstream isolates to specific species using multilocus sequence analysis
      (MLSA), by sequencing the quinolone resistance-determining regions (QRDRs) of
      gyrA, gyrB, parC and parE, and by testing strain susceptibility to various
      fluoroquinolones. Non-susceptibility to one or more fluoroquinolones was observed
      for 78% of isolates, however only 68.7% of patients were receiving
      fluoroquinolone prophylaxis. All but one of the determinative QRDR polymorphisms
      occurred in GyrA or ParC, yet the pattern of determinative QRDR polymorphisms was
      significantly associated with the fluoroquinolone prophylaxis received. By
      combining MLSA and QRDR data, multiple patients infected with genetically
      indistinguishable fluoroquinolone-resistant Streptococcus mitis or Streptococcus
      oralis strains were discovered. Together these data delineate the molecular
      mechanisms of fluoroquinolone resistance in VGS isolates causing bacteraemia and
      suggest possible transmission of fluoroquinolone-resistant S. mitis and S. oralis
      isolates among cancer patients. 

PMID- 24721232
TI  - Nanocarriers for antibiotics: a promising solution to treat intracellular
      bacterial infections.
AB  - In the field of antibiotherapy, intracellular infections remain difficult to
      eradicate mainly due to the poor intracellular penetration of most of the
      commonly used antibiotics. Bacteria have quickly understood that their
      intracellular localisation allows them to be protected from the host immune
      system, but also from the action of antimicrobial agents. In addition, in most
      cases pathogens nestle in professional phagocytic cells, and can even use them as
      a 'Trojan horse' to induce a secondary site of infection thereby causing
      persistent or recurrent infections. Thus, new strategies had to be considered in
      order to counteract these problems. Amongst them, nanocarriers loaded with
      antibiotics represent a promising approach. Nowadays, it is possible to
      encapsulate, incorporate or even conjugate biologically active molecules into
      different families of nanocarriers such as liposomes or nanoparticles in order to
      deliver antibiotics intracellularly and hence to treat infections. This review
      gives an overview of the variety of nanocarriers developed to deliver antibiotics
      directly into infected cells. 

PMID- 24721233
TI  - Selection and characterisation of Staphylococcus aureus mutants with reduced
      susceptibility to the investigational oxazolidinone MRX-I.
AB  - MRX-I is a new oxazolidinone antimicrobial under development. In this study, the
      potential for development of resistance to MRX-I in Staphylococcus aureus was
      investigated and key mutations were characterised. Determination of spontaneous
      resistance frequency and the mutant selection window (MSW) were performed with
      meticillin-susceptible S. aureus (MSSA) ATCC 29213, meticillin-resistant S.
      aureus (MRSA) ATCC 33591 and two clinical MRSA isolates SA 0016 and SA 0017.
      Selected resistant mutants were sequenced for 23S rRNA as well as genes encoding
      the ribosomal proteins L3, L4 and L22. Resistance frequencies for the
      aforementioned strains were <8.25*10(-12), <6.33*10(-12), <2.96*10(-13) and
      <4.52*10(-13), respectively, and the MSW of MRX-I was 2-4, 1-4, 1-2 and 1-4 mg/L,
      respectively. After 30 serial passages, MRX-I minimum inhibitory concentrations
      (MICs) increased up to 8- to 16-fold both against MSSA and MRSA, whilst linezolid
      MICs increased 128-fold against MSSA and 16- to 32-fold against MRSA. MRX-I
      resistance mutations were clustered mainly in 23S rRNA and L3 protein regions.
      The U2504A transversion in 23S rRNA dominated in MRX-I-resistant mutants. No
      mutations in L4 and L22 proteins were observed. MRX-I exhibits a low potential to
      develop resistance in S. aureus, with a reduced resistance propensity compared
      with linezolid.

PMID- 24721234
TI  - Prediction of major antibiotic resistance in Escherichia coli and Klebsiella
      pneumoniae in Singapore, USA and China using a limited set of gene targets.
AB  - Antibiotic resistance in Gram-negative bacteria, especially Enterobacteriaceae,
      can be conferred by a large number of different acquired resistance genes,
      although it appears that relatively few dominate. A previous survey of
      Escherichia coli and Klebsiella pneumoniae isolates from Sydney, Australia,
      revealed that a limited set of genes could reliably predict resistance to third
      generation cephalosporins (3GCs) and aminoglycosides. Here we tested E. coli and
      K. pneumoniae isolates with a cefotaxime, ceftriaxone and/or ceftazidime minimum
      inhibitory concentration of >= 2 MUg/mL from China and Singapore, with
      significantly higher resistance rates than Australia, as well as the USA. Few
      targets were needed to predict non-susceptibility to 3GCs (95/95; 100%) and
      gentamicin (47/51; 92%). The gene types detected here are consistent with
      previous surveys in similar countries with similar resistance rates, where the
      majority of 3GC resistance can be explained by blaCTX-M genes. This study
      identified a limited set of genes capable of predicting resistance to 3GC and
      aminoglycoside antibiotics and implies a restriction in the global resistance
      gene pool that can be exploited for diagnostic purposes.

PMID- 24721235
TI  - Carbosilane dendrimers as gene delivery agents for the treatment of HIV
      infection.
AB  - Despite the use of siRNA in the downregulation of HIV-1 replication which has
      been reported, CD4 T lymphocytes are difficult to transfect with non-viral
      vectors. We determined whether second generation carbosilane dendrimers (2G-NN16
      and 2G-03NN24) may be efficient transfectants in CD4 T lymphocytes. Dendrimers
      were also tested on macrophages to determine whether they can modify macrophage
      phenotype and induce an inflammatory response. The nanoconjugate formed by 2G
      03NN24/siRNA-Nef presents the highest inhibition of HIV-1 replication. Dendrimers
      presented safety properties because they did not induce proliferation on CD4 T
      lymphocytes and decrease the release of TNFalpha and IL-12p40 by macrophages.
      Both dendrimers also decrease the phagocytosis activity. Additionally, 2G-03NN24
      dendrimer decreases the CCL2 and CCR2 expression in macrophages. Carbosilane
      dendrimers 2G-NN16 and 2G-03NN24 can be used as efficient non-viral vectors for
      gene therapy applications, mainly in the treatment of HIV infection. 

PMID- 24721236
TI  - Trend of microbiologically-confirmed tuberculosis in a low-incidence setting with
      high immigration rates.
AB  - BACKGROUND: The metropolitan area of Bologna, a city in Northern Italy (Emilia
      Romagna region), is considered a low incidence setting for TB, but has a high
      rate of foreign immigration (13.5% official resident immigrants relative to the
      whole population in 2011). The aim of this study was to describe the
      epidemiological trend of TB, focusing on differences between Italian and foreign
      born cases. METHODS: We examined all bacteriologically confirmed TB cases
      identified in the Microbiology Unit of Bologna University Hospital from January
      2008 and December 2011. We compared demographic, clinical and microbiological
      data for Italian vs. foreign-born TB cases. RESULTS: Out of 255 TB cases
      identified during the study period, 168 (65.9%) were represented by foreign-born
      cases. The proportion of immigrants with TB progressively increased over the
      study period (from 60.8% in 2008 to 67.5% in 2011). Although foreign-born cases
      were significantly younger than Italian cases (mean age 32.3+/-14.4 years vs
      61.9+/-21.5 years), the mean age among the latter decreased from 71.2 in 2008 to
      54.6 years in 2011 (p=0.036).Concerning TB localization, 65.9% (n=168) had
      pulmonary TB (P-TB) and 34.1% (n=87) extra-pulmonary TB (EP-TB). In this study,
      35.6% of Italian-born P-TB cases were smear positive, versus 51.4% of foreign
      born P-TB cases. The highest proportion of high-grade positive microscopy P-TB
      was among subjects between 25-34 years old (36.9%; p=0.004).Mono-resistance to
      isoniazid (mono-H) was found among 9.2% and 10.1% of Italian and foreign-born
      cases, respectively. Among Italian cases, resistance to H and any other first
      line drug (poly-H) and Multidrug resistant TB (MDR-TB) were 4.6% and 1.2%,
      respectively. In foreign-born cases poly-H (12.8%) and MDR-TB (6.9%)
      significantly increased over the time (p=0.003 and p=0.007, respectively). The
      proportion of MDR-TB was significantly higher among immigrants from Eastern
      Europe (10.9%) compared to Italian-born patients (p=0.043). All (n=9) MTB strains
      resistant to four or five first line drugs and Extensively drug resistant (XDR
      TB) strains were from foreign-born cases. CONCLUSIONS: TB epidemiology in a low
      incidence setting is strongly influenced by immigration rates. Ethnicity, mean
      age, and incidence of MDR-TB among foreign-born cases reflect immigration trends
      in Northern Italy.

PMID- 24721237
TI  - The electrogenic cardiac sodium bicarbonate co-transporter (NBCe1) contributes to
      the reperfusion injury.
AB  - BACKGROUND: Although the participation of the electrogenic sodium/bicarbonate
      cotransporter (NBCe1) in the recovery from an intracellular acid load is
      recognized, its role in ischemia-reperfusion is still unclear. METHODS AND
      RESULTS: Our objective was to assess the role of NBCe1 in reperfusion injury. We
      use selective functional antibodies against extracellular loop 3 (a-L3) and loop
      4 (a-L4) of NBCe1. a-L3 inhibits and a-L4 stimulates NBCe1 activity. Isolated rat
      hearts were submitted to 40 min of coronary occlusion and 1 h of reperfusion. a
      L3, a-L4 or S0859--selective Na(+)-HCO3(-) co-transport inhibitor--were
      administered during the initial 10 min of reperfusion. The infarct size (IS) was
      measured by triphenyltetrazolium chloride staining technique. Postischemic
      systolic and diastolic functions were also assessed. a-L3 and S0859 treatments
      decreased significantly (P < .05) the IS (16 +/- 3% for a-L3 vs. 32 +/- 5% in
      hearts treated with control nonimmune serum and 19 +/- 3% for S0859 vs. 39 +/- 2%
      in untreated hearts). Myocardial function during reperfusion improved after a-L3
      treatment, but it was not modified by S0859. The infusion of a-L4 did not modify
      neither the IS nor myocardial function. CONCLUSIONS: The NBCe1 hyperactivity
      during reperfusion leads to Na(+) and Ca(2+) loading, conducing to Ca(2+)
      overload and myocardial damage. Consistently, we have shown herein that the
      selective NBCe1 blockade with a-L3 exerted cardioprotection. This beneficial
      action strongly suggests that NBCe1 could be a potential target for the treatment
      of coronary disease.

PMID- 24721239
TI  - [The fusion protein of cytoplasmic transduction peptide (CTP)-HBcAg18-27-Tapasin
      enhances specific immune response to hepatitis B virus and inhibits viral
      replication in transgenic mice].
AB  - OBJECTIVE: To investigate the effect of protein transduction domain-hepatitis B
      virus core antigen (CTP-HBcAg18-27)-Tapasin fusion protein-induced specific
      cytotoxic T lymphocyte (CTL) response on hepatitis B virus (HBV) replication in
      HBV transgenic mice. METHODS: Twenty HBV-transgenic mice were randomly divided
      into two groups for a 3-week course of once weekly subcutaneous immunizations
      with either CTP-HBcAg18-27-Tapasin fusion protein or CTP-HBcAg18-27. Mice
      administered isotonic saline served as blank controls. Expressions of cytokines
      in splenocytes were analyzed by flow cytometry. Serum levels of hepatitis B
      surface antigen (HBsAg) and HBV DNA were determined by microparticle enzyme
      immunoassay and real-time fluorescent PCR assay, respectively. Expression of
      HBsAg in hepatic tissues was detected by immunohistochemistry. RESULTS:
      Immunization with 100 mug of CTP-HBcAg18-27-Tapasin fusion protein led to a
      significant increase in proportions of CTLs in spleen (2.70%+/-0.20% vs. 50 mug
      of CTP-HBcAg18-27-Tapasin: 1.66%+/-0.53%, 50 mug of CTP-HBcAg18-27: 1.26%+/
      0.56%, and blank controls: 0.75%+/-0.71%; F = 741.45, P = 0.000) and up
      regulation of inflammatory cells in hepatic tissue. In addition, both
      immunizations of CTP-HBcAg18-27-Tapasin led to significant decreases in serum
      HBsAg and HBV DNA levels compared to those in the CTP-HBcAg18-27 group.
      CONCLUSION: HBV-related modification of the expression of the molecular chaperone
      Tapasin may affect its interaction with intracellular antigen peptides, thereby
      leading to increases the number of specific CTLs in the spleen, decreases in
      serum HBsAg and HBV DNA levels, and down-regulation of HBsAg expression in
      hepatic tissue. These results obtained in HBV-transgenic mice suggest that the
      CTP-HBcAg18-27-Tapasin fusion protein has anti-HBV activity.

PMID- 24721238
TI  - Radial glial progenitors repair the zebrafish spinal cord following transection.
AB  - In mammals, spinal cord injury results in permanent sensory-motor loss due in
      part to a failure in reinitiating local neurogenesis. However, zebrafish show
      robust neuronal regeneration and functional recovery even after complete spinal
      cord transection. Postembryonic neurogenesis is dependent upon resident
      multipotent progenitors, which have been identified in multiple vertebrates. One
      candidate cell population for injury repair expresses Dbx1, which has been shown
      to label multipotent progenitors in mammals. In this study, we use specific
      markers to show that cells expressing a dbx1a:GFP reporter in the zebrafish
      spinal cord are radial glial progenitors that continue to generate neurons after
      embryogenesis. We also use a novel larval spinal cord transection assay to show
      that dbx1a:GFP(+) cells exhibit a proliferative and neurogenic response to
      injury, and contribute newly-born neurons to the regenerative blastema. Together,
      our data indicate that dbx1a:GFP(+) radial glia may be stem cells for the
      regeneration of interneurons following spinal cord injury in zebrafish. 

PMID- 24721240
TI  - [Therapeutic efficacy and quality of life investigation of traditional Chinese
      medicine-based therapy of chronic hepatitis B-related liver fibrosis].
AB  - OBJECTIVE: To prospectively evaluate the efficacy of a traditional Chinese
      medicine (TCM)-based therapy for treating liver fibrosis in patients with chronic
      hepatitis B (CHB), and to investigate the patients' perception of the treatment's
      effects on quality of life (QoL). METHODS: A total of 430 patients with CHB
      related liver fibrosis were randomly assigned to treatment groups for receipt of
      a 12-month course of the antiviral drug entecavir alone (control group) or in
      combination with the TCM Liuweiwuling tablets. Patients were assessed before (pre
      treatment) and after therapy and the treatment-related differences in clinical
      manifestations, levels of liver function markers and liver fibrosis indexes,
      color ultrasound images, and hepatitis B virus (HBV) DNA load were compared
      between the two groups by statistical analysis. The generic QoL scale developed
      by the World Health Organization (WHOQOL-BREF) was used to score the patients'
      perceptions of treatment outcome. RESULTS: After treatment, the patients in both
      groups showed significant improvement in the majority of clinical manifestations
      (both P less than 0.05), with the exception of bloating. In addition, both groups
      showed significant improvements of liver function markers and in signs of liver
      fibrosis (both P less than 0.05). Both groups also showed significant reductions
      in the diameters of the portal and splenic (both P less than 0.05), as well as
      increases in the rate of undetectable HBV DNA (with a statistically similar
      outcome achieved in the two groups). Finally, both groups had higher QoL scores
      after treatment, with all assessed parameters except environment showing a
      significant improvement (all P less than 0.05). CONCLUSION: When used in
      combination with entecavir, the TCM Liuweiwuling tablet is a safe therapy for CHB
      and its related liver fibrosis and may help to improve the QoL of these patients.

PMID- 24721241
TI  - [A case-control study on the risk factors of hepatocellular carcinoma in Guizhou
      Province].
AB  - OBJECTIVE: To determine the risk factor of HCC in Guizhou. METHODS: A group case
      control study design was conducted between 762 cases and 798 controls in Guizhou
      province. The main related-factors were analyzed with unconditional logistic
      regression model and evaluated by odds ratio (OR) and 95% confidence interval
      (95% CI). RESULTS: There are significant differences between cases and controls
      in regarding to cigarette smoking 210 (27.6%),non-alcoholic fatty liver disease
      336 (44.1%), alcoholic liver disease 245 (32.2%), family history of HCC 141
      (16.5%), alcohol consumption 300 (39.4%), HBV infection 436 (57.2%), pickled food
      290 (38.1%), and economic status 5 years ago 420 (55.1%) in cases,and cigarette
      smoking 116 (14.5%),non-alcoholic fatty liver disease 160 (20.1%), alcoholic
      liver disease 101 (12.7%), family history of HCC 40 (5.0%), alcohol consumption
      180 (22.6%), HBV infection 82 (10.3%), pickled food 225 (28.2%), and economic
      status 5 years ago 647 (81.1%) in controls, with OR of each variable was 3.520,
      2.464, 4.330, 2.219, 2.451, 19.245, 6.212, 0.174 respectively, P less than 0.01.
      CONCLUSION: HBV infection and pickled food were the most common risks for HCC in
      Guizhou. Alcohol consumption excessively and cigarette smoking may increase the
      risk too.

PMID- 24721242
TI  - [Hepatitis B reactivation after treatment for HBV-related hepatocellular
      carcinoma: comparative analysis of radiofrequency ablation versus hepatic
      resection].
AB  - OBJECTIVE: To perform a comparative analysis of the reactivation rate of
      hepatitis B virus (HBV) infection and related risk factors after treatment of HBV
      related hepatocellular carcinoma (HCC) by radiofrequency ablation (RFA) or
      hepatic resection. METHODS: We retrospectively analyzed the HBV reactivation rate
      and related risk factors of a cohort of 218 patients treated for HBV-related HCC
      between August 2008 and August 2011; the study population consisted of 125
      patients who received RFA and 93 patients who received hepatic resection.
      Comparisons were made using the unpaired Student's t-test for continuous
      variables and the x2-test and Fisher's exact test for categorical variables.
      Univariate and multivariate logistic regression analysis was used to assess risk
      factors. RESULTS: Twenty patients showed HBV reactivation following treatment,
      but the incidence was significantly lower in the RFA group than in the hepatic
      resection group (5.6% vs. 14.0%, 7/125 vs. 13/93, x2 = 4.492, P = 0.034). The
      univariate and multivariate analysis indicated that no antiviral therapy (OR =
      11.7; 95% CI: 1.52-90.8, P = 0.018) and the treatment type (i.e. RFA or hepatic
      resection) (OR = 3.36; 95% CI: 1.26-8.97, P = 0.016) were significant risk
      factors of HBV reactivation. Subgroup analysis showed that the incidence of HBV
      reactivation was lower in patients who received antiviral therapy than in those
      who did not for both the RFA group and the hepatic resection group but the
      difference was not significant in the former group (1/68 vs. 19/150, x2=7.039, P
      = 0.008 and 0/33 vs. 7/92, x2 = 2.660, P = 0.188, respectively). However, the
      incidence of HBV reactivation in patients who did not receive antiviral therapy
      was higher than in those who did receive antiviral therapy in the hepatic
      resection group (12/58 vs. 1/35, x2 = 5.773, P = 0.027). CONCLUSION: The
      incidence of HBV reactivation was lower in patients who received RFA than in
      those who received hepatic resection to treat HBV-related HCC. Antiviral therapy
      prior to the hepatic resection treatment may be beneficial for reducing the
      incidence of HBV reactivation.

PMID- 24721243
TI  - [Meta-analysis of branched chain amino acid-enriched nutrition to improve hepatic
      function in patients undergoing hepatic operation].
AB  - OBJECTIVE: To perform a meta-analysis of randomized controlled trials (RCTs)
      assessing the benefit of providing branched chain amino acid (BCAA)-enriched
      nutrition to improve hepatic function in patients undergoing hepatic operation.
      METHODS: The electronic databases of PubMed, Springerlink, the Chinese Biomedical
      Database (CBM), the Cochrane Library, and the China National Knowledge
      Infrastructure (CNKI) were searched for relevant RCTs using the following search
      terms: nutritional support, enteral nutrition, parenteral nutrition,
      hepatic/liver surgery, liver cirrhosis, cancer, hepatectomy, and liver
      transplantation. The quality of the retrieved RCTs was assessed according to the
      scale developed by the Cochrane Collaboration. The meta-analysis was conducted
      using RevMan software, version 5.2. RESULTS: A total of 11 relevant RCTs,
      representing 510 patients, were included in the meta-analysis. Compared to
      patients in the control (normal nutrition) group, the patients in the BCAA group
      experienced an effective improvement in hepatic function, as evidenced by
      significant decreases in total bilirubin (by 0.07 mumol/L; 95% confidence
      interval (CI): -0.18 to 0.05, P more than 0.05]. In addition, the BCAA group
      showed improvements in plasma levels of albumin (weighted mean difference (WMD) =
      0.07; 95% CI: 0.06, 0.24, P less than 0.05) and alanine aminotransferase (WMD =
      +5.61; 95% CI: -8.63 to 19.86, P more than 0.05] but neither of the changes
      reached the threshold of a statistically significant improvement. The BCAA group
      did however show significantly lower complication rate after operation (65%, 95%
      CI: 0.48, 0.87, P less than 0.01] and mean duration of hospital stay (4.61 days;
      95% CI: -6.61, -2.61, P less than 0.01]. CONCLUSION: BCAA-enriched nutrition
      improves hepatic function in patients undergoing hepatic operation, thereby
      helping to reduce the complication risk, duration of hospital stay, and financial
      burden. BCAA-enriched nutrition is a safe and effective therapy and further
      clinical application may be beneficial.

PMID- 24721244
TI  - [SCD1 over-expression inhibits palmitic acid-induced apoptosis of rat BRL
      hepatocytes].
AB  - OBJECTIVE: To investigate the protective mechanism of stearoyl-CoA desaturase 1
      (SCD1) over-expression against the pro-apoptotic affects of palmitic acid on
      hepatocytes using the rat BRL cell line. METHODS: Concentration effect curves
      were generated using the trypan blue exclusion test to assess the death rate of
      BRL cells upon exposure to a dilution series of palmitic acid. The multiplicity
      of infection (MOI) of a lentiviral expression vector, pGC-FU-GFP, was determined
      for the BRL cells. Unmanipulated BRL cells were divided into two groups: the non
      palmitate groups were composed of ordinary cultured cells (CON) alone, infected
      with lentivirus empty expression vector (negative control, NC), and infected with
      lentivirus overexpressing SCD1 (SCD1-LV); the palmitate groups were composed of
      ordinary cultured cells plus palmitate (CON+) alone, infected with lentivirus
      empty expression vector plus palmitate (NC+), and infected with lentivirus
      overexpressing SCD1 plus palmitate (SCD1-LV+). SCD1 mRNA expression was detected
      by real-time PCR. Propidium iodide (PI) single-staining was used to detect
      apoptosis and assess the cell cycle. Inter-group differences were analyzed
      statistically. RESULTS: The death rate of BRL cells increased significantly after
      72 h of exposure to 400 mumol/L palmitate (P less than 0.01). The MOI of pGC-FU
      GFP in BRL cells was 20. The expression of SCD1 was significantly higher in the
      SCD1-LV and SCD1-LV+ groups than in the respective controls (vs. CON: F = 289, P
      less than 0.01; vs. CON+: F = 1522, P less than 0.01). Palmitate exposure led to
      decreased expression of SCD1 (CON+ vs. CON, F = 22, P less than 0.05 and NC+ vs.
      NC: F = 34, P less than 0.05). The ratio of S stage cells was similar in all non
      palmitate groups (CON, NC and SCD1-LV, P = 0.137). However, there was a
      significant apoptotic peak and lower ratio of S stage cells in the control
      palmitate groups (CON+ and NC+) and the activity of cell proliferation was
      decreased as well. The ratio of apoptotic cells was decreased significantly in
      the SCD1-LV+ group compared to the CON+ group (P less than 0.01). CONCLUSION: The
      expression of SCD1 and its desaturation activity increased in BRL cells upon
      infection with the pGC-FU-SCD1-GFP lentiviral vector, suggesting that SCD1 over
      expression can decrease palmitic acid-induced toxicity and apoptosis in
      hepatocytes.

PMID- 24721245
TI  - [Relationship between normal serum uric acid levels and nonalcoholic fatty liver
      disease in postmenopausal women].
AB  - OBJECTIVE: To analyze the relationship between normal serum uric acid (SUA)
      levels and nonalcoholic fatty liver disease (NAFLD) among postmenopausal women,
      and determine the possible risk factors of NAFLD in this patient population.
      METHODS: Chinese postmenopausal women who participated in the annual health check
      up program from March 2009 to February 2010 were retrospectively assessed to
      identify individuals with SUA within normal range for study inclusion. For the
      total 1425 study participants, the recorded data of anthropometric parameters,
      metabolic factors, and serum biochemical parameters were collected. Results from
      abdominal ultrasonography examination were used to group participants according
      to presence of fatty liver. Women with fatty liver were divided into NAFLD and
      non-NAFLD groups. Further sub-grouping was performed according to SUA quartiles,
      as follows: Q1 group: less than 226.1 mumol/L); Q2 group: 226.1 mumol/L less than
      or equal to SUA less than 267.8 mumol/L; Q3 group: 267.8 mumol/Lless than or
      equal to SUA less than 303.5 mumol/L); Q4 group: 303.5 mumol/Lless than or equal
      toSUAless than or equal to357.0 mumol/L. The independent-sample t-test was used
      to compare normally distributed variables between groups, and the Mann-Whitney U
      test was used to analyze variables with skewed distribution. Categorical
      variables were examined by the R * C x2 test. Binary logistic analysis was used
      to determine the risk factors for fatty liver and to adjust for possible
      confounders. The multiple non-parameter independent-sample test (Kruskal-Wallis
      test) was used to compare the differences of SUA levels among NAFLD groups with
      different disease severity. RESULTS: The prevalence of NAFLD among Chinese
      postmenopausal women with normal SUA was 32.8%, with NAFLD prevalences of 20.4%
      (70/343) in women with Q1 SUA, 26.3% (104/395) with Q2 SUA, 35.2% (128/364) with
      Q3 SUA, and 51.4% (166/323) with Q4 SUA. The prevalence of fatty liver showed a
      significant increasing trend according to the SUA quartile (x2 = 76.470, P-trend
      less than 0.01). Women in the SUA Q3 and Q4 groups had significantly higher risk
      of fatty liver presence than women in the Q1 group (P less than 0.01 for both,
      with or without adjustment of confounders). Disease severity did not appear to be
      related to disease severity, as the SUA levels in women with mild, moderate or
      severe fatty liver were not significantly different (286.8+/-48.2 mumol/L vs.
      277.9+/-53.0 mumol/L vs. 281.4+/-48.2 mumol/L, respectively; x2 = 3.025, P more
      than 0.05). CONCLUSION: SUA levels were independently correlated with NAFLD in
      Chinese postmenopausal women. SUA levels in the higher quartiles of the normal
      range may be an independent risk factor of NAFLD.

PMID- 24721246
TI  - [Protective role of gammadelta T cells in concanavalin A-induced liver injury].
AB  - OBJECTIVE: To investigate the role played by gammadelta T cells in acute liver
      injury using the concanavalin A (ConA)-induced liver injury mouse model. METHODS:
      Acute liver injury was induced by intravenous injection of 10 mug/g of ConA into
      male C57BL/6J mice with wild-type or T cell receptor-gamma knockout (TCR delta-/
      ) genetic backgrounds. Mice injected with PBS alone served as negative controls.
      The degree of liver damage was assessed by measuring serum levels of transaminase
      and cytokines at post-injection hours 3, 6, 12, 24, 48, and 72. The percentage of
      gammadelta T cells and proportions of different subsets in liver lymphocytes were
      measured by flow cytometry. RESULTS: The TCR delta-/- mice showed significantly
      higher levels of the inflammatory cytokines IFN-gamma, TNFalpha and IL-4 than the
      wild-type mice at post-injection hour 3. The percentage of liver gammadelta T
      cells increased with increased injury degree, and the extent of increase was
      significantly higher in the TCR delta-/- mice than the wild-type mice (post
      injection hour 6: 6302.61+/-592.06 vs. 1319.26+/-355.48, 12: 6569.44+/-1060.98
      vs. 3415.53+/-343.90, 24: 6514.29+/-757.26 vs. 2062.73+/-365.67, 48: 1262.61+/
      558.07 vs. 113.66+/-113.26, and 72: 226.54+/-98.20 vs. 42.35+/-21.51 U/L; all P
      less than 0.05). In addition, compared to the negative control mice, the ConA
      induced mice showed a higher proportions of Vgamma4 gammadelta T cells to total
      gammadelta T cells (17.78+/-2.95 vs. 25.26+/-2.43) and to total liver lymphocytes
      (0.47+/-0.07 vs. 0.66+/-0.05). Similarly, compared to the negative control mice,
      the ConA-induced mice showed a higher proportion of Vgamma1 gammadelta T cells to
      total gammadelta T cells (38.37+/-6.10 vs. 50.19+/-5.52) but the proportion to
      total liver lymphocytes was not significantly different among the groups (0.76+/
      0.18 vs. 0.78+/-0.25). Reinfusion of Vgamma4 gammadelta T lymphocytes into TCR
      delta-/- mice led to lower serum ALT levels than reinfusion of Vgamma1 gammadelta
      T lymphocytes (5054.10+/-1748.51 vs. 12333.56+/-663.535 U/L). CONCLUSION:
      gammadelta T cells play a protective role in ConA-induced liver injury and this
      effect maybe mediated by the Vgamma4 gammadelta T cell subset.

PMID- 24721247
TI  - Cellular reprogramming in skin cancer.
AB  - Early primitive stem cells have long been viewed as the cancer cells of origin
      (tumor initiating target cells) due to their intrinsic features of self-renewal
      and longevity. However, emerging evidence suggests a surprising capacity for
      normal committed cells to function as reserve stem cells upon reprogramming as a
      consequence of tissue damage resulting in inflammation and wound healing. This
      results in an alternative concept positing that tumors may originate from
      differentiated cells that can re-acquire stem cell properties due to genetic or
      epigenetic reprogramming. It is likely that both models are correct, and that a
      continuum of potential cells of origin exists, ranging from early primitive stem
      cells to committed progenitor or even terminally differentiated cells. A
      combination of the nature of the target cell and the specific types of gene
      mutations introduced determine tumor cell lineage, as well as potential for
      malignant conversion. Evidence from mouse skin models of carcinogenesis suggests
      that initiated cells at different stages within a stem cell hierarchy have
      varying degrees of requirement for reprogramming (e.g. inflammation stimuli),
      depending on their degree of differentiation. This article will present evidence
      in favor of these concepts that has been developed from studies of several mouse
      models of skin carcinogenesis. 

PMID- 24721248
TI  - Cubital tunnel syndrome: comparative results of a multicenter study of 4 surgical
      techniques with a mean follow-up of 92 months.
AB  - BACKGROUND: Cubital tunnel syndrome is the second most frequent entrapment
      syndrome. Physiopathology is mixed, and treatment options are multiple, none
      having yet proved superior efficacy. OBJECTIVES: The present retrospective
      multicenter study compared results and rates of complications and recurrence
      between the 4 main cubital tunnel syndrome treatments, to identify trends and
      optimize outcome. MATERIALAND METHODS: Patients presenting with primary clinical
      cubital tunnel syndrome diagnosed on electroneuromyography were included and
      operated on using 1 of the following 4 techniques: open or endoscopic in situ
      decompression, or subcutaneous or submuscular anterior transposition. Four
      specialized upper-limb surgery centers participated, each systematically
      performing 1 of the above procedures. Subjective and objective results and rates
      of complications and recurrence were compared at end of follow-up. RESULTS: Five
      hundred and two patients were included and 375 followed up for a mean 92 months
      (range, 9-144 months); 103 were lost to follow-up and 24 died. Whichever the
      procedure, more than 90% of patients were cured or showed improvement. There was
      a single case of scar pain at end of follow-up, managed by endoscopic
      decompression; there were no other long-term complications. None of the 4
      techniques aggravated symptoms. There were 6 recurrences by end of follow-up: 1
      associated with open in situ decompression and 5 with submuscular transposition.
      CONCLUSION: Surgery was effective in treating cubital tunnel syndrome.
      Submuscular anterior transposition was associated with recurrence. In contrast to
      literature reports, subcutaneous anterior transposition, which is a reliable and
      valid technique, was not associated with a higher complication rate than in situ
      decompression. LEVEL OF EVIDENCE: Level IV. Multicenter retrospective.

PMID- 24721249
TI  - The progression of lumbar curves in adolescent Lenke 1 scoliosis and the distal
      adding-on phenomenon.
AB  - INTRODUCTION: The postoperative deterioration of the curve below spinal fusion
      instrumentation resulting in a distal adding-on (AO) phenomenon in idiopathic
      adolescent scoliosis (IAS) frequently requires surgical revision with
      disappointing secondary clinical results. HYPOTHESIS: Analysis of AP (coronal)
      range of motion (cROM) and lateral (sagittal) range of motion (sROM) on dynamic
      (side-bending, flexion, extension) X-rays to determine the choice of the lowest
      instrumented vertebra (LIV) can help reduce distal adding-on. The goal of this
      study was to study the postoperative progression of the lumbar curve in Lenke 1
      scoliosis operated on with a LIV based on dynamic X-ray results. MATERIALS AND
      METHODS: Right-sided Lenke 1 IAS that was treated surgically by posterior
      arthrodesis alone with a follow-up of at least 2 years was included in the study.
      The following radiographic parameters were evaluated: the Cobb angles of the
      curves, reducibility of the curves, the apex of the scoliosis, the central sacral
      vertical line, the stable vertebra (SV), the neutral vertebra (NV), the distances
      between the CSVL and the centroids of the LIV and of the first vertebra below
      instrumentation, as well as the tilt of the superior endplates. sROM and cROM
      were determined on dynamic X-rays. RESULTS: Fifty IAS were evaluated/185 files.
      Only three cases fulfilled the criteria for AO including two that were secondary
      to peri- or postoperative complications. The lumbar curve presented with a loss
      of correction of 0.9 degrees  at one year and 1.14 degrees  at the final follow
      up. None of the parameters studied were correlated to the deterioration of the
      lumbar curve. DISCUSSION: The choice of the LIV has been shown to influence the
      deterioration of the lumbar curve and the development of AO. The choice of the
      LIV based on an analysis of AP (coronal) and lateral (sagittal) range of motion
      seems to prevent the development of AO. LEVEL OF EVIDENCE: 4, retrospective
      study.

PMID- 24721250
TI  - Supramalleolar osteotomy: techniques, indications and outcomes in a series of 83
      cases.
AB  - INTRODUCTION: Supramalleolar osteotomy is an alternative surgical procedure for
      the management of asymmetric early arthritis of the ankle. The main goal of this
      retrospective study was to evaluate the clinical and radiological benefits of
      supramalleolar osteotomy. The secondary goal was to identify prognostic factors
      to help decide upon this therapeutic indication. MATERIALS AND METHODS: Eighty
      three patients, mean age 45 years old (17-79), presenting with post-traumatic
      asymmetric early arthritis of the ankle were followed up for a mean 3.5 years (1
      14 years). Sixty-two patients presented with a varus deformity (mean: 13 degrees
      ), and 21 with a valgus deformity (mean: 17.5 degrees ). The presence of a
      preoperative clinical 'sidewalk sign' was looked for and it was considered
      positive if pain improved when the patient walked on a surface slope that was
      tilted in the opposite direction of their deformity. A functional preoperative
      evaluation and at the final follow-up were performed using the American
      Orthopedic Foot and Ankle Society (AOFAS) ankle-hind foot scale. The frontal
      deformity was measured by the Meary angle on a weight-bearing X-ray. Varus
      deformities were treated by a lateral closing wedge supramalleolar osteotomy or a
      medial opening wedge supramalleolar osteotomy. Valgus deformities were treated by
      a lateral opening wedge or a medial closing wedge supramalleolar osteotomy.
      RESULTS: At last follow-up, the mechanical axis in the varus group was 1.3
      degrees  and 7.5 degrees  in the valgus group. The AOFAS score significantly
      improved (P<0.001) by 15 points in patients with a varus deformity and 13 points
      in patients with a valgus deformity. A positive sidewalk sign (disappearance of
      pain) was correlated with a good outcome and had a positive predictive value of
      0.88 (CI: 0.77-0.95) (P<0.001). DISCUSSION: The supramalleolar osteotomy is a
      conservative therapeutic surgical option for the management of arthritis of the
      ankle associated with varus or valgus deformities. The results are satisfactory
      for indications of arthritis with varus and valgus deformities and a positive
      'sidewalk' sign (pain relief on a slope surface tilted in the opposite direction
      of the deformity). LEVEL OF EVIDENCE: Level IV: retrospective case series.

PMID- 24721251
TI  - Questions of trust in health research on social capital: what aspects of personal
      network social capital do they measure?
AB  - Health research on personal social capital has often utilized measures of
      respondents' perceived trust of others as either a proxy for one's social capital
      in the absence of more focused measures or as a subjective component of social
      capital. Little empirical work has evaluated the validity of such practices. We
      test the construct validity of two trust measures used commonly in health
      research on social capital-generalized trust and trust of neighbors-with respect
      to measures of people's general network-, organization-, family-, friend-, and
      neighborhood-based social capital and the extent to which these two trust
      measures are associated with self-rated general health and mental health when
      social capital measures are included in the same models. Analyses of 2008
      Canadian General Social Survey data (response rate 57.3%) indicate that
      generalized trust and trust of neighbors are both positively-yet modestly
      associated with measures of several domains of network-based social capital. Both
      trust measures are positively associated with general and mental health, but
      these associations remain robust after adjusting for social capital measures. Our
      findings suggest that (a) trust is conceptually distinct from social capital, (b)
      trust measures are inadequate proxies for actual personal social networks, and
      (c) trust measures may only be capturing psychological aspects relevant to-but
      not indicative of-social capital. Though links between perceived trust and health
      deserve study, health research on social capital needs to utilize measures of
      respondents' actual social networks and their inherent resources. 

PMID- 24721252
TI  - Recent achievements in developing the biocatalytic toolbox for chiral amine
      synthesis.
AB  - Novel enzyme activities and chemoenzymatic reaction concepts have considerably
      expanded the biocatalytic toolbox for chiral amine synthesis. Creating new
      activities or extending the scope of existing enzymes by protein engineering is a
      common trend in biocatalysis and in chiral amine synthesis specifically. For
      instance, an amine dehydrogenase that allows for the direct asymmetric amination
      of ketones with ammonia was created by mutagenesis of an l-amino acid
      dehydrogenase. Another trend in chiral amine chemistry is the development of
      strategies allowing for the synthesis of secondary amines. For example the smart
      choice of substrates for amine transaminases provided access to secondary amines
      by chemoenzymatic reactions. Furthermore novel biocatalysts for the synthesis of
      secondary amines such as imine reductases and Pictet-Spenglerases have been
      identified and applied. Recent examples showed that the biocatalytic amine
      synthesis is emerging from simple model reactions towards industrial scale
      preparation of pharmaceutical relevant substances, for instance, as shown in the
      synthesis of a Janus kinase 2 inhibitor using an amine transaminase. A comparison
      of important process parameters such as turnover number and space-time yield
      demonstrates that biocatalytic strategies for asymmetric reductive amination are
      maturing and can already compete with established chemical methods. 

PMID- 24721253
TI  - More than genes: the advanced fetal programming hypothesis.
AB  - Many lines of data, initial epidemiologic studies as well as subsequent extensive
      experimental studies, indicate that early-life events play a powerful role in
      influencing later suceptibility to certain chronic diseases. Such events might be
      over- or undernutrition, exposure to environmental toxins, but also changes in
      hormones, in particular stress hormones. Typically, those events are triggered by
      the environmental challenges of the mother. However, recent studies have shown
      that paternal environmental or nutritional factors affect the phenotype of the
      offspring as well. The maternal and paternal environmental factors act on the
      phenotype of the offspring via epigenetic modification of its genome. The
      advanced fetal programming hypothesis proposes an additional non-environmentally
      driven mechanism: maternal and also paternal genes may influence the maturating
      sperm, the oocyte, and later the embryo/fetus, leading to their epigenetic
      alteration. Thus, the observed phenotype of the offspring may be altered by
      maternal/paternal genes independent of the fetal genome. Meanwhile, several
      independent association studies in humans dealing with metabolic and neurological
      traits also suggest that maternal genes might affect the offspring phenotype
      independent of the transmission of that particular gene to the offspring.
      Considering the implications of this hypothesis, some conclusions drawn from
      transgenic or knockout animal models and based on the causality between a genetic
      alteration and a phenotype, need to be challenged. Possible implications for the
      development, diagnostic and therapy of human genetic diseases have to be
      investigated.

PMID- 24721254
TI  - How often does the operating list follow the planned order? An analysis of
      elective maxillofacial operating lists.
AB  - OBJECTIVES: The authors explored consistency of the observed running order in
      operating sequence compared with prior scheduled listing. We analysed potential
      variables felt to be predictive in the chances of a patient having their
      procedure as previously scheduled. METHODS: Data were retrospectively collected
      for a consecutive group of patients who underwent elective maxillofacial
      procedures over a four week period. The consistency of scheduled and observed
      running order was documented. We considered four independent variables (original
      list position, day of week, morning or afternoon list, seniority of surgeon) and
      analysed their relationship to the probability of a patient undergoing their
      operation as per listing. Logistic regression analysis was used to determine
      significant associations between predictor variables with an altered list order.
      RESULTS: Data were available for 35 lists (n = 133). 49% of lists were found to
      run according to prior given order, the remainder subject to some alteration.
      Logistic regression analysis showed a statistically significant association
      between original scheduled position and day of week, with list position
      consistency. Patients listed first were twelve times more likely to have their
      operation as listed compared to those placed fourth (OR 12.7, 95% CI 3.7-43, p <
      0.05). Operating lists at the start of a week were subject to less alteration (p
      < 0.05). There was no demonstrated relationship between the grade of surgeon
      operating and alteration in operating sequence. CONCLUSION: Approximately half of
      lists showed some alteration to the previously printed order. It appears that
      being first on an elective list offers the greatest guarantee that a patient will
      have their operation as per prior schedule. It may be reasonable for clinicians
      to be mindful of potential operating list alterations when preparing their
      patients for elective surgery.

PMID- 24721255
TI  - Role of manipulation knowledge in routine tool use.

PMID- 24721256
TI  - Prevalence, molecular characterization and zoonotic potential of Cryptosporidium
      spp. in goats in Henan and Chongqing, China.
AB  - To estimate the prevalence and public health significance of cryptosporidiosis in
      goats in China, 1265 fecal samples from seven farms in Henan province and
      Chongqing city were examined for Cryptosporidium oocysts. The overall infection
      rate of Cryptosporidium spp. was 3.48% (44/1256). Significant difference was
      observed among age groups, with the post weaned kids having the highest infection
      rate (4.58%; rho<0.01). Cryptosporidium spp. were characterized by PCR
      restriction fragment length polymorphism (RFLP) analysis and DNA sequence
      analysis of the small subunit (SSU) rRNA gene. The SSU rRNA-based PCR identified
      three Cryptosporidium species, including Cryptosporidium ubiquitum (24/44) in
      Henan and Chongqing, and Cryptosporidium andersoni (16/44) and Cryptosporidium
      xiaoi (4/44) in Henan. Among which, the C. ubiquitum and C. andersoni were first
      identified in goats thus far and were found in all age groups except no C.
      andersoni being found in the postparturition nannies, whereas the C. xiaoi was
      detected in pre-weaned kids and pregnant nannies. Subtyping C. ubiquitum by DNA
      sequence analysis of the 60 kDa glycoprotein (gp60) gene suggested the isolates
      identified all belonged to zoonotic XIIa subtype 2. Thus, the dominant C.
      ubiquitum found in this study and the XIIa subtype 2 has been found in humans
      indicated goats are a potential source for zoonotic infections with the C.
      ubiquitum. More studies are needed for better understanding of differences in the
      transmission and public health significance of cryptosporidiosis in goats.

PMID- 24721257
TI  - Encystment of Vermamoeba (Hartmannella) vermiformis: Effects of environmental
      conditions and cell concentration.
AB  - Vermamoeba vermiformis is a free-living amoeba (FLA) which is widely distributed
      in the environment. It is known to colonize water systems and to be a reservoir
      of pathogenic bacteria, such as Legionella pneumophila. For these reasons the
      control of V. vermiformis represents an important health issue. However, FLA may
      be resistant to disinfection treatments due to the process of encystment.
      Thereby, it is important to better understand factors influencing this process.
      In this aim, we investigated the effect of temperature, pH, osmotic pressure and
      cell concentration on the encystment of two V. vermiformis strains. Encystment
      was quite fast, with a 100% encystment rate being observed after 9h of
      incubation. For the two strains, an optimal encystment was obtained at 25 and 37
      degrees C. Concerning pH and osmotic pressure, there were different effects on
      the encystment according to the tested strains. For the reference strain (ATCC
      50237), the patterns of encystment were similar for pH comprised between 5 and 9
      and for KCl concentrations ranging from 0.05 to 0.2 mol L(-1). For the
      environmental strain (172A) an optimal encystment was obtained for basic pH (8
      and 9) and for a concentration in KCl of 0.1 mol L(-1). The results also clearly
      demonstrated that the encystment rate increased with cell concentration,
      suggesting that there is an inter-amoebal communication. The present study
      establish for the first time environmental conditions favoring encystment and
      would lay the foundations to better control the encystment of V. vermiformis.

PMID- 24721258
TI  - Naegleria fowleri: contact-dependent secretion of electrondense granules (EDG).
AB  - The free living amoeba Naegleria fowleri is pathogenic to humans but also to
      other mammalians. These amoebae may invade the nasal mucosa and migrate into the
      brain causing cerebral hemorrhagic necrosis, a rapidly fatal infection. Knowledge
      of the cytolytic mechanism involved in the destruction of brain tissues by
      Naegleria trophozoites is limited. In other amoebic species, such as Entamoeba
      histolytica, we have previously reported the possible lytic role of small
      cytoplasmic components endowed with proteolytic activities, known as
      electrondense granules (EDG). Using transmission electron microscopy we now
      report that EDG, seldom found in long term cultured N. fowleri, are present in
      abundance in trophozoites recovered from experimental mice brain lesions.
      Numerous EDG were also observed in amoebae incubated with collagen substrates or
      cultured epithelial cells. SDS-PAGE assays of concentrated supernatants of these
      trophozoites, containing EDG, revealed proteolytic activities. These results
      suggest that EDG may have a clear role in the cytopathic mechanisms of this
      pathogenic amoeba. 

PMID- 24721259
TI  - Activity of Thymus vulgaris essential oil against Anisakis larvae.
AB  - Anisakiasis is an important food-borne disease especially in countries with high
      fish consumption. The increase of cases of human disease and the virtual absence
      of effective treatments have prompted the research on new active compounds
      against Anisakis larvae. As well known, the disease is related to the consumption
      of raw or almost raw seafood products, but also marinated and/or salted fishery
      products, if the processing is insufficient to destroy nematode larvae can
      represent a risks for the consumers. In the light of the biocidal efficacy
      against different pathogens demonstrated for various essential oils, the aim of
      this work is to evaluate the effect of Thymus vulgaris essential oil (TEO)
      against anisakidae larvae. The TEO at 10% and 5% concentration in oil sunflower
      seeds, caused in vitro the death of all larvae within 14 h, with cuticle and
      intestinal wall damages. The results obtained showing a significant activity
      against Anisakis larvae, suggest further investigation on TEO as a larvicidal
      agent and on its potential use in the industrial marinating process.

PMID- 24721260
TI  - Accuracy of body fat percent and adiposity indicators cut off values to detect
      metabolic risk factors in a sample of Mexican adults.
AB  - BACKGROUND: Although body fat percent (BF%) may be used for screening metabolic
      risk factors, its accuracy compared to BMI and waist circumference is unknown in
      a Mexican population. We compared the classification accuracy of BF%, BMI and WC
      for the detection of metabolic risk factors in a sample of Mexican adults;
      optimized cutoffs as well as sensitivity and specificity at commonly used BF% and
      BMI international cutoffs were estimated. We also estimated conditional BF% means
      at BMI international cutoffs. METHODS: We performed a cross-sectional analysis of
      data on body composition, anthropometry and metabolic risk factors(high glucose,
      high triglycerides, low HDL cholesterol and hypertension) from 5,100 Mexican men
      and women. The association between BMI, WC and BF%was evaluated with linear
      regression models. The BF%, BMI and WC optimal cutoffs for the detection of
      metabolic risk factors were selected at the point where sensitivity was closest
      to specificity. Areas under the ROC Curve (AUC) were compared among classifiers
      using a non-parametric method. RESULTS: After adjustment for WC, a 1% increase in
      BMI was associated with a BF% rise of 0.05 percentage points (p.p.) in men
      (P<0.05) and 0.25 p.p. in women (P<0.001). At BMI=25.0 predicted BF% was 27.6+/
      0.16 (mean+/-SE) in men and 41.2+/-0.07 in women. Estimated BF% cutoffs for
      detection of metabolic risk factors were close to 30.0 in men and close to 44.0
      in women. In men WC had higher AUC than BF% for the classification of all
      conditions whereas BMI had higher AUC than BF% for the classification of high
      triglycerides and hypertension. In womenBMI and WC had higher AUC than BF% for
      the classification of all metabolic risk factors. CONCLUSIONS: BMI and WC were
      more accurate than BF% for classifying the studied metabolic disorders.
      International BF% cutoffs had very low specificity and thus produced a high rate
      of false positives in both sexes.

PMID- 24721261
TI  - Brief interventions for illicit drug use among peripartum women.
AB  - We review the evidence and identify limitations of the current literature on the
      effectiveness of brief interventions (<=5 intervention sessions) on illicit drug
      use, treatment enrollment/retention, and pregnancy outcomes among pregnant and
      postpartum women; and consider this evidence in the context of the broader brief
      intervention literature. Among 4 published studies identified via systematic
      review and meeting a priori quality criteria, we found limited, yet promising
      evidence of the benefit of brief interventions to reduce illicit drug use among
      postpartum women. Two of the 4 randomized controlled trials tested similar
      computer-delivered single-session interventions; both demonstrate effects on
      postpartum drug use. Neither of the 2 randomized controlled trials that assessed
      treatment use found differences between intervention and control groups. Studies
      examining brief interventions for smoking and alcohol use among pregnant women,
      and for illicit drug use in the general adult population, have shown small but
      statistically significant results of the effectiveness of such interventions.
      Larger studies, those that examine the effect of assessment alone on illicit drug
      use, and those that use technology-delivered brief interventions are needed to
      assess the effectiveness of brief interventions for drug use in the peripartum
      period. 

PMID- 24721262
TI  - Clinical utility of postoperative hemoglobin level testing following total
      laparoscopic hysterectomy.
AB  - OBJECTIVE: To determine the clinical utility of hemoglobin level testing in
      guiding postoperative care following total laparoscopic hysterectomies performed
      for benign indications. STUDY DESIGN: Retrospective cohort study. RESULTS: A
      total of 629 women underwent total laparoscopic hysterectomies during the 24
      month study period. Only 16 (2.5%) developed symptoms and/or signs suggestive of
      hemodynamic compromise. When compared to asymptomatic patients, symptomatic
      patients had a larger decrease in postoperative hemoglobin level (2.66 vs
      1.80g/dL, P = .007) and were more likely to undergo blood transfusion, pelvic
      imaging or reoperation (P < .001). Women with a smaller body mass index and/or
      higher intraoperative intravenous fluid volume were more likely to have a larger
      decrease in postoperative hemoglobin level (P < .05). Past surgical history,
      duration and complexity of the hysterectomy, estimated surgical blood loss,
      uterine weight, and perioperative use of intravenous ketorolac were not
      associated with a greater decrease in postoperative hemoglobin (P > .05). Using
      the University of Pittsburgh Medical Center's annual laparoscopic hysterectomy
      rate and insurance companies' reimbursement for blood hemoglobin testing, we
      estimated the national annual cost for hemoglobin testing following total
      laparoscopic hysterectomy to be $2,804,662. CONCLUSION: Hemoglobin level testing
      has little clinical benefit following elective total laparoscopic hysterectomy
      and should be reserved for patients who develop signs or symptoms suggestive of
      acute anemia. Heath care cost savings can be substantial if this test is no
      longer routinely requested following total laparoscopic hysterectomies.

PMID- 24721263
TI  - Cannabinoid receptor type 1 immunoreactivity and disease severity in human
      epithelial ovarian tumors.
AB  - OBJECTIVE: In light of recent findings indicating that endocannabinoid system has
      antitumor actions, our study aimed to localize it in the human epithelial ovarian
      tumors, highlighting the differences among benign, borderline, and invasive forms
      and correlating cannabinoid receptor type 1 (CB1R) expression with disease
      severity. STUDY DESIGN: We determined CB1R immunohistochemical expression in 66
      epithelial ovarian tumors treated in the Department of Woman, Child, and General
      and Specialized Surgery, Second University of Naples, at S. Maria del Popolo
      degli Incurabili Hospital (Naples): 36 borderline ovarian tumors, the main target
      of interest being intermediate forms, 15 benign and 15 invasive ovarian tumors.
      RESULTS: The benign ovarian tumors showed a weak expression of CB1R in the 33% of
      the cases and moderate expression in the 67% of the cases. Borderline ovarian
      tumors had a similar trend. They showed weak CB1R expression in 28% of the cases,
      moderate expression in 53% of the cases, and strong expression in 19% of the
      cases. In contrast, invasive tumors showed a weak expression of CB1R in 7% of the
      cases, moderate expression in 20% of the cases, and strong expression in 73% of
      the cases. CONCLUSION: The recorded data show that the expression of CB1R
      increased from benign and borderline to malignant tumors. In the near future,
      endocannabinoid receptors might be used in clinical practice, alone or in
      combination with other markers, to identify or better characterize ovarian
      tumors, without considering the great opportunity that they might represent as
      therapeutic targets.

PMID- 24721264
TI  - Genetic epidemiology of pelvic organ prolapse: a systematic review.
AB  - Given current evidence supporting a genetic predisposition for pelvic organ
      prolapse, we conducted a systematic review of published literature on the genetic
      epidemiology of pelvic organ prolapse. Inclusion criteria were linkage studies,
      candidate gene association and genome-wide association studies in adult women
      published in English and indexed in PubMed through Dec. 2012, with no limit on
      date of publication. Methodology adhered to the PRISMA guidelines. Data were
      systematically extracted by 2 reviewers and graded by the Venice criteria for
      studies of genetic associations. A metaanalysis was performed on all single
      nucleotide polymorphisms evaluated by 2 or more studies with similar methodology.
      The metaanalysis suggests that collagen type 3 alpha 1 (COL3A1) rs1800255
      genotype AA is associated with pelvic organ prolapse (odds ratio, 4.79; 95%
      confidence interval, 1.91-11.98; P = .001) compared with the reference genotype
      GG in populations of Asian and Dutch women. There was little evidence of
      heterogeneity for rs1800255 (P value for heterogeneity = .94; proportion of
      variance because of heterogeneity, I(2) = 0.00%). There was insufficient evidence
      to determine whether other single nucleotide polymorphisms evaluated by 2 or more
      papers were associated with pelvic organ prolapse. An association with pelvic
      organ prolapse was seen in individual studies for estrogen receptor alpha (ER
      alpha) rs2228480 GA, COL3A1 exon 31, chromosome 9q21 (heterogeneity logarithm of
      the odds score 3.41) as well as 6 single nucleotide polymorphisms identified by a
      genome-wide association study. Overall, individual studies were of small sample
      size and often of poor quality. Future studies would benefit from more rigorous
      study design as outlined in the Venice recommendations.

PMID- 24721265
TI  - Physiological regulation of lipoprotein lipase.
AB  - The enzyme lipoprotein lipase (LPL), originally identified as the clearing factor
      lipase, hydrolyzes triglycerides present in the triglyceride-rich lipoproteins
      VLDL and chylomicrons. LPL is primarily expressed in tissues that oxidize or
      store fatty acids in large quantities such as the heart, skeletal muscle, brown
      adipose tissue and white adipose tissue. Upon production by the underlying
      parenchymal cells, LPL is transported and attached to the capillary endothelium
      by the protein GPIHBP1. Because LPL is rate limiting for plasma triglyceride
      clearance and tissue uptake of fatty acids, the activity of LPL is carefully
      controlled to adjust fatty acid uptake to the requirements of the underlying
      tissue via multiple mechanisms at the transcriptional and post-translational
      level. Although various stimuli influence LPL gene transcription, it is now
      evident that most of the physiological variation in LPL activity, such as during
      fasting and exercise, appears to be driven via post-translational mechanisms by
      extracellular proteins. These proteins can be divided into two main groups: the
      liver-derived apolipoproteins APOC1, APOC2, APOC3, APOA5, and APOE, and the
      angiopoietin-like proteins ANGPTL3, ANGPTL4 and ANGPTL8, which have a broader
      expression profile. This review will summarize the available literature on the
      regulation of LPL activity in various tissues, with an emphasis on the response
      to diverse physiological stimuli. 

PMID- 24721266
TI  - [Global threats, waste recycling and the circular economy concept].

PMID- 24721267
TI  - Toxocariasis: seroprevalence in abandoned-institutionalized children and infants.
AB  - Toxocariasis is an infection that has worldwide distribution. Toxocara canis is
      the most relevant agent due to its frequent occurrence in humans. Soil
      contamination with embryonated eggs is the primary source of T. canis. This study
      aimed to determine the seroprevalence of toxocariasis in 10-month to 3 year-old
      abandoned infants, considered to be at high risk because of their orphanhood
      status and early age. Blood samples were collected from 120 children
      institutionalized in an orphanage in the city of La Plata. In this study, we
      observed 38.33% of seropositive cases for T. canis by ELISA and 45% by Western
      blot techniques; significant differences among groups A (<1 year), B (1-2 years)
      and C (>2 years) were also found. In research group A, children presented a
      seropositivity rate of 23.91%, in group B of 42.85% and in group C of 56%, which
      indicates an increase in frequency as age advances, probably because of greater
      chances of contact with infective forms of the parasite since canines and soil
      are frequently infected with T. canis eggs. Abandoned children come from poor
      households, under highly unsanitary conditions resulting from inadequate or lack
      of water supply and sewer networks, and frequent promiscuity with canines, which
      promotes the occurrence of parasitic diseases. These children are highly
      vulnerable due to their orphanhood status and age. 

PMID- 24721268
TI  - [Knowledge of zoonoses transmission routes and of the species concerned among
      rural workers].
AB  - The aim of this study was to evaluate the level of awareness of zoonoses among
      rural workers and their potential associations with socio-demographic factors. A
      cross-sectional study was performed by holding personal interviews (N=110, n=94)
      using a structured questionnaire. The statistical analysis included the chi(2)
      test, the Student's t test and Pearson and Spearman correlations. The highest
      level of awareness was found for trichinosis, rabies and scabies. Species
      transmitting brucellosis, tuberculosis and anthrax were well known, but not their
      modes of transmission. The least known diseases were toxocariasis and
      hydatidosis, followed by leptospirosis and toxoplasmosis. Significant
      associations were found (p<0.001) between the knowledge of transmitting species
      and the modes of transmission. Senior male owners, married, and living in urban
      areas showed the highest overall knowledge of zoonoses. Awareness of zoonoses
      among rural workers is inadequate. Veterinarians in conjunction with risk
      insurers may play a key role in providing information to people at risk. 

PMID- 24721269
TI  - [Pneumococcal meningitis in children under 15 years of age in Misiones
      (Argentina). Sixteen year's epidemiological surveillance].
AB  - We report the results of pneumococcal meningitis surveillance conducted at the
      Provincial Pediatric Hospital of Posadas, Misiones (Argentina), before the
      conjugate vaccine was introduced into the national vaccination schedule. Between
      January 1994 and December 2009, 167 cases of Streptococcus pneumoniae meningitis
      were diagnosed in children aged 1 month to 15 years. The attack rate/100,000
      children ranged from 19.2 (1997) to 4.3 (2009), with a mean of 10.6 and a
      tendency to decrease (y=-0.689x+16.52). The number of cases per 100,000 children
      decreased from 146.6 to 34.8 and particularly involved the group of children aged
      1 to 11 months (94/167, 56%). Thirty point seven percent (30.7%) (46/150) of the
      isolates were resistant to penicillin whereas 16.7% (25/150) were non-susceptible
      to cefotaxime. beta-lactam resistance increased as from 1997 and began to decline
      in 2005. Nineteen serotypes were detected; type 14 was predominant and accounted
      for 32% (40/125). Eighty four point eight percent (84.8%) of the isolates were
      circumscribed to nine serotypes: 14, 5, 1, 7F, 18C, 6B, 9N, 9V and 4. Theoretical
      coverage for patients aged <2 years and >2 years was 84.1% (74/88) and 83.8%
      (31/37) for the 10-valent vaccine and 89.8 % (79/88) and 83.8% (31/37) for the 13
      valent vaccine respectively. Penicillin resistance was restricted to 8 serotypes
      (14, 6B, 6A, 9V, 4, 23B, 19A1) and nonsusceptibility to cefotaxime was
      circumscribed to 3 serotypes (14, 9V and 1). This study will allow to evaluate
      the impact of the implementation of conjugate vaccines on our area.

PMID- 24721270
TI  - [Retrospective study of the implementation of the qualitative PCR technique in
      biological samples for monitoring toxoplasmosis in pediatric patients receiving
      hematopoietic stem cell transplantation].
AB  - Toxoplasmosis is an opportunistic infection caused by the parasite Toxoplasma
      gondii. The infection is severe and difficult to diagnose in patients receiving
      allogeneic hematopoietic stem cell transplantation (HSCT). Twelve patients
      receiving HSCT were monitored post-transplant, by qualitative PCR at the
      Children's Hospital S.A.M.I.C. "Prof. Dr. Juan P. Garrahan". The monitoring of
      these patients was defined by a history of positive serology for toxoplasmosis in
      the donor or recipient and because their hematologic condition did not allow the
      use of trimethoprim-sulfamethoxazole for prophylaxis. During the patients'
      monitoring, two of them with positive PCR results showed signs of illness by T.
      gondii and were treated with pyrimethamine-clindamycin. In two other patients,
      toxoplasmosis was the cause of death and an autopsy finding, showing negative PCR
      results. Four patients without clinical manifestations received treatment for
      toxoplasmosis because of positive PCR detection. In four patients there were no
      signs of toxoplasmosis disease and negative PCR results during follow-up. The
      qualitative PCR technique proved useful for the detection of toxoplasmosis
      reactivation in HSCT recipients, but has limitations in monitoring and making
      clinical decisions due to the persistence of positive PCR over time and
      manifestations of toxicity caused by the treatment. 

PMID- 24721271
TI  - First detection of CMY-2 plasmid mediated beta-lactamase in Salmonella Heidelberg
      in South America.
AB  - Salmonella enterica serovar Heidelberg ranks among the most prevalent causes of
      human salmonellosis in the United States and Canada, although it has been
      infrequently reported in South American and European countries. Most Salmonella
      infections are self-limiting; however, some invasive infections require
      antimicrobial therapy. In this work we characterized an oxyimino-cephalosporin
      resistant S. Heidelberg isolate recovered from an inpatient in a Buenos Aires
      hospital. CMY-2 was responsible for the beta-lactam resistance profile. S.
      Heidelberg contained a 97kb plasmid belonging to the Inc N group harboring blaCMY
      2. ISEcp1 was located upstream blaCMY-2 driving its expression and mobilization.
      The isolate belonged to sequence type 15 and virotyping revealed the presence of
      sopE gene. In this study we identified the first CMY-2 producing isolate of S.
      Heidelberg in Argentina and even in South America. 

PMID- 24721272
TI  - Wild-type minimal inhibitory concentration distributions in bacteria of animal
      origin in Argentina.
AB  - The aim of this study was to determine the antimicrobial resistance profiles of
      indicator bacteria isolated from domestic animal feces. Minimal inhibitory
      concentration (MIC) was determined by agar dilution. Interpretative criteria on
      the basis of wild-type MIC distributions and epidemiological cutoff values (ECOFF
      or ECV) were used according to the 'European Committee on Antimicrobial
      Susceptibility Testing' (EUCAST) data. Results from 237 isolates of Escherichia
      coli showed reduced susceptibility for ampicillin, streptomycin and tetracycline,
      the antimicrobials commonly used in intensive breeding of pigs and hens.
      Regarding all the species of the genus Enterococcus spp., there are only ECOFF or
      ECV for vancomycin. Of the 173 Enterococcus spp. isolated, only one showed
      reduced susceptibility to vancomycin and was classified as 'non-wild-type' (NWT)
      population. This is the first report in Argentina showing data of epidemiological
      cutoff values in animal bacteria. 

PMID- 24721273
TI  - [Fusarium graminearum presence in wheat samples for human consumption].
AB  - One of the most important diseases in cereal crops is Fusarium head blight, being
      Fusarium graminearum the main etiological agent. This fungus has the ability to
      produce a wide spectrum and quantity of toxins, especially deoxynivalenol (DON).
      During the last crop season (2012-2013) the climatic conditions favored Fusarium
      colonization. The objective of this work was to determine the presence of this
      fungus as well as the DON content in 50 wheat grain samples. Our results showed
      that 80% of the samples were contaminated with Fusarium graminearum. Twenty four
      percent (24%) of the samples contained >= 1MUg/g DON, 26% ranged from 0,5 and
      0,99MUg/g, and the remaining 50% had values lower than 0,5MUg/g. Correlation was
      found between the presence of Fusarium graminearum and DON. It is necessary to
      establish DON limit values in wheat grains for human consumption.

PMID- 24721275
TI  - Natural occurrence of entomophthoroid fungi of aphid pests on Medicago sativa L.
      in Argentina.
AB  - Four species of entomophthoroid fungi, Pandora neoaphidis (Entomophthorales:
      Entomophthoraceae), Zoophthora radicans (Entomophthorales: Entomophthoraceae),
      Entomophthora planchoniana (Entomophthorales: Entomophthoraceae) and Neozygites
      fresenii (Neozygitales: Neozygitaceae) were found to infect Aphis craccivora,
      Therioaphis trifolii, and Acyrthosiphon pisum and unidentified species of
      Acyrthosiphon on lucerne in Argentina. Samples were collected from five sites
      (Ceres, Rafaela, Sarmiento, Monte Vera and Bernardo de Irigoyen) in the province
      of Santa Fe. In this study, Zoophthora radicans was the most important pathogen
      and was recorded mainly on Acyrthosiphon sp. Zoophthora radicans was successfully
      isolated and maintained in pure cultures. This study is the first report of
      entomophthoroid fungi infecting lucerne (Medicago sativa L.) aphids in Argentina.

PMID- 24721274
TI  - Molecular evidence of Chlamydophila pneumoniae infection in reptiles in
      Argentina.
AB  - In the central area of Argentina, the epidemiological and molecular
      characteristics of Chlamydophila pneumoniae infections in reptiles are still
      unknown. A nested polymerase chain reaction of the rpoB gene was used to detect
      C. pneumoniae in cloacal swab samples from 19 reptiles at a recreational area.
      Eleven (57.89%) reptiles were positive; the sequencing and phylogenetic analysis
      confirmed the presence of this bacterium. Neither C. pneumoniae DNA in the
      caregivers pharynges nor IgM antibodies anti-C. pneumoniae in their serum samples
      were detected; however, caregivers presented very high titers of IgG anti-C.
      pneumoniae. The detection of C. pneumoniae DNA in reptiles demonstrated the
      circulation of this agent in the recreational area and could be responsible for
      the exacerbated immune response of the personnel handling the reptiles, which
      suggests a potential zoonotic cycle. This is the first report of the detection of
      C. pneumoniae in reptiles in Argentina.

PMID- 24721276
TI  - [Serological survey of antibodies against viral diseases of public health
      interest in llamas (Lama glama) from Jujuy province, Argentina].
AB  - Llama population from Argentina is mainly concentrated in the Andean Puna, Jujuy.
      Llamas represent an important economic resource for the Andean communities. The
      aim of this study was to investigate the prevalence of antibodies against viral
      antigens associated to viral diseases of economic impact (neonatal diarrhea,
      reproductive and respiratory syndromes). A total of 349 serum samples from adult
      llamas were analyzed. The obtained antibody prevalence was 100 % for Rotavirus A
      and 70 % for Bovine parainfluenza virus 3. In contrast, no reactors were detected
      to Bovine herpesvirus 1, Bovine viral diarrhea virus 1, Human influenza A virus
      (H1N1) and Equine influenza virus (H3N8). These results confirm the wide
      circulation of rotavirus and parainfluenza virus in Argentinean llamas and
      suggest that susceptibility to infection with bovine herpesvirus, pestivirus and
      influenza A viruses is low. This serologic survey provides novel information
      regarding the epidemiology of viral diseases affecting llamas from the
      Argentinean Andean Puna. 

PMID- 24721277
TI  - [The antihypertensive effect of fermented milks].
AB  - There is a great variety of fermented milks containing lactic acid bacteria that
      present health-promoting properties. Milk proteins are hydrolyzed by the
      proteolytic system of these microorganisms producing peptides which may also
      perform other functions in vivo. These peptides are encrypted within the primary
      structure of proteins and can be released through food processing, either by milk
      fermentation or enzymatic hydrolysis during gastrointestinal transit. They
      perform different activities, since they act in the cardiovascular, digestive,
      endocrine, immune and nervous systems. Bioactive peptides that have an
      antihypertensive, antithrombotic, antioxidant and hypocholesterolemic effect on
      the cardiovascular system can reduce the risk factors for chronic disease
      manifestation and help improve human health. Most studied bioactive peptides are
      those which exert an antihypertensive effect by inhibiting the angiotensin
      converting enzyme (ACE). Recently, the study of these peptides has focused on the
      implementation of tests to prove that they have an effect on health. This paper
      focuses on the production of ACEinhibitory antihypertensive peptides from
      fermented milks, its history, production and in vivo tests on rats and humans, on
      which its hypotensive effect has been shown. 

PMID- 24721278
TI  - Sleep tight: exploring the relationship between sleep and attachment style across
      the life span.
AB  - Based on early life experiences in which developmental, genetic, and
      environmental components interact, humans learn to trust themselves and others
      and connect emotionally in consistent ways that are broadly defined as
      "attachment styles." These relatively stable patterns of interpersonal
      interaction are associated with either vulnerability to various health risks or
      resilience. Similarly, the mechanisms involved in sleep regulation undergo
      developmental changes that overlap temporally with attachment formation and
      remain sensitive to a series of biological, environmental and psychological
      influences. Interestingly, while sleep has been conceptualized as a fundamental
      attachment behavior given its dyadic context, few studies have explored its
      relationship with attachment style in various ages. We present the first
      systematic review of the published literature examining the relationship between
      attachment style and sleep in humans across the life span. While levels of
      evidence and methods of assessment vary significantly, the results suggest a
      possible life-long relationship between individual attachment style and sleep.
      These findings are particularly useful in understanding relatively ingrained
      psychological mechanisms that can affect and be affected by sleep. Clinical and
      research implications are discussed. 

PMID- 24721279
TI  - Decreased processing speed might account for working memory span deficit in
      schizophrenia, and might mediate the associations between working memory span and
      clinical symptoms.
AB  - OBJECTIVE: Verbal working memory span is decreased in patients with
      schizophrenia, and this might contribute to impairment in higher cognitive
      functions as well as to the formation of certain clinical symptoms. Processing
      speed has been identified as a crucial factor in cognitive efficiency in this
      population. We tested the hypothesis that decreased processing speed underlies
      the verbal working memory deficit in patients and mediates the associations
      between working memory span and clinical symptoms. METHOD: Forty-nine
      schizophrenia inpatients recruited from units for chronic and acute patients, and
      forty-five healthy participants, were involved in the study. Verbal working
      memory span was assessed by means of the letter-number span. The Digit Copy test
      was used to assess motor speed, and the Digit Symbol Substitution Test to assess
      cognitive speed. RESULTS: The working memory span was significantly impaired in
      patients (F(1,90)=4.6, P<0.05). However, the group difference was eliminated when
      either the motor or the cognitive speed measure was controlled (F(1,89)=0.03,
      P=0.86, and F(1,89)=0.03, P=0.88). In the patient group, working memory span was
      significantly correlated with negative symptoms (r=-0.52, P<0.0001) and thought
      disorganisation (r=-0.34, P<0.025) scores. Regression analyses showed that the
      association with negative symptoms was no longer significant when the motor speed
      measure was controlled (beta=-0.12, P=0.20), while the association with thought
      disorganisation was no longer significant when the cognitive speed measure was
      controlled (beta=-0.10, P=0.26). CONCLUSIONS: Decrement in motor and cognitive
      speed plays a significant role in both the verbal working memory impairment
      observed in patients and the associations between verbal working memory
      impairment and clinical symptoms.

PMID- 24721280
TI  - A 5-year prospective study of predictors for functional and work disability among
      primary care patients with depressive disorders.
AB  - OBJECTIVE: To study prevalence of and predictors for functional and work
      disability among primary care (PC) patients with depressive disorders in
      prospective long-term follow-up. METHODS: The Vantaa Primary Care Depression
      Study followed up prospectively 137 patients with depressive disorders for 5
      years with a life chart. Information on level of functioning in general and in
      different dimensions, employment, sick leaves and disability pensions were
      obtained from interviews and patient records. RESULTS: Level of functioning and
      work ability were strongly associated with time spent depressed and/or current
      severity of depression. Patients who belonged to the labour force at baseline
      spent one-third of the follow-up off work due to depression; two-thirds were
      granted sick leaves, and one-tenth a disability pension due to depression. Longer
      duration of depression, co-morbid disorders and having received social assistance
      predicted dropping out from work. CONCLUSION: Duration of depressive episodes
      appears decisive for long-term disability among PC patients with depression.
      Patients spent one-third of the follow-up off work due to depression, and
      remaining outside the labour force is a common outcome. Psychiatric and somatic
      co-morbidities, education and socio-economic means influence the level of
      functioning and ability to work, but are not equally important for all areas of
      life.

PMID- 24721281
TI  - Antibody therapy can enhance AngiotensinII-induced myocardial fibrosis.
AB  - BACKGROUND: Myocardial fibrosis is a pathological process that is characterized
      by disrupted regulation of extracellular matrix proteins resulting in permanent
      scarring of the heart tissue and eventual diastolic heart failure. Pro-fibrotic
      molecules including transforming growth factor-beta and connective tissue growth
      factor are expressed early in the AngiotensinII (AngII)-induced and other models
      of myocardial fibrosis. As such, antibody-based therapies against these and other
      targets are currently under development. RESULTS: In the present study, C57Bl/6
      mice were subcutaneously implanted with a mini-osmotic pump containing either
      AngII (2.0 MUg/kg/min) or saline control for 3 days in combination with mIgG (1
      mg/kg/d) injected through the tail vein. Fibrosis was assessed after picosirius
      red staining of myocardial cross-sections and was significantly increased after
      AngII exposure compared to saline control (11.37 +/- 1.41%, 4.94 +/- 1.15%; P
      <0.05). Non-specific mIgG treatment (1 mg/kg/d) significantly increased the
      amount of fibrosis (26.34 +/- 3.03%; P <0.01). However, when AngII exposed
      animals were treated with a Fab fragment of the mIgG or mIgM, this exacerbation
      of fibrosis was no longer observed (14.49 +/- 2.23%; not significantly different
      from AngII alone). CONCLUSIONS: These data suggest that myocardial fibrosis was
      increased by the addition of exogenous non-specific antibodies in an Fc-mediated
      manner. These findings could have substantial impact on the future experimental
      design of antibody-based therapeutics.

PMID- 24721282
TI  - Spectroscopic and structural investigations of iron(III) isothiocyanates. A
      comparative theoretical and experimental study.
AB  - A combined experimental and theoretical study on the molecular structure and
      vibrational spectra of [Fe(NCS)](2+) complex in the aqueous solution at the pH~2
      +/- 0.1 have been performed. Experimental Raman spectra of the iron(III)
      isothiocyanate with higher coordination number in the acidic aqueous solution
      have been analyzed. Molecular modeling of the iron(III) monoisothiocyanate
      complex was accomplished by the density functional theory (DFT) method using
      B3LYP and PBE1PBE functionals. Theoretical vibrational spectra of the iron(III)
      monoisothiocyanate were interpreted by means of the potential energy
      distributions (PEDs). The influence of different solvation models and position of
      SO4(2)(-) ligand vs. NCS(-) ligand upon its geometry and vibrational frequencies
      have been evaluated. The effect of H2O/D2O isotopic substitution on the
      experimental and calculated Raman spectra of iron(III) isothiocyanates has been
      examined. Procedures of Raman spectra subtraction have been applied for the
      extractions of weak and/or obscured Raman signals. As a result, the presence of
      bound SO4(2)(-) ion and water molecules in the first coordination sphere in the
      acidic aqueous iron(III) isothiocyanate solution was confirmed. The vibrational
      assignments for the investigated iron(III) isothiocyanates were proposed here for
      the first time.

PMID- 24721283
TI  - UV-Vis spectroscopic study and DFT calculation on the solvent effect of
      trimethoprim in neat solvents and aqueous mixtures.
AB  - The solvatochromic behavior of trimethoprim (TMP) was analyzed using UV-Vis
      spectroscopy and DFT methods in neat and binary aqueous solvent mixtures. The
      effects of solvent dipolarity/polarizability and solvent-solute hydrogen bonding
      interactions on the absorption maxima were evaluated by means of the linear
      solvation energy relationship concept of Kamlet and Taft. This analysis indicated
      that both interactions play an important role in the position of the absorption
      maxima in neat solvents. The simulated absorption spectra of TMP and
      TMP:(solvent)n complexes in ACN and H2O using TD-DFT methods were in agreement
      with the experimental ones. Binary aqueous mixtures containing as co-solvents
      DMSO, ACN and EtOH were studied. Preferential solvation was detected as a
      nonideal behavior of the wavenumber curve respective to the analytical mole
      fraction of co-solvent in all binary systems. TMP molecules were preferentially
      solvated by the organic solvent over the whole composition range. Index of
      preferential solvation, as well as the influence of solvent parameters were
      calculated as a function of solvent composition. 

PMID- 24721284
TI  - Systems approach to identify environmental exposures contributing to organ
      specific carcinogenesis.
AB  - BACKGROUND: The most effective way to reduce cancer burden is Q2 prevention which
      is dependent on identifying individuals at risk for a particular cancer and
      counseling them to avoid exposure to causative agents. Other than a few well
      characterized environmental agents linked to specific cancers, linkage between
      any particular environmental exposure and a specific type of cancer is mostly
      unknown. Thus, we propose a systems approach to analyze publicly available large
      datasets to identify candidate agents that play a role in organ-specific
      carcinogenesis. METHODS: Publicly available datasets for mRNA and miRNA
      expression in ovarian cancer were queried to define the differentially expressed
      genes that are also targets of differentially expressed miRNAs. These target
      genes were then used to query the Comparative Toxicogenomics Database to identify
      interacting chemicals and also were analyzed by Ingenuity Pathway Analysis to
      identify pathways. RESULTS: The interacting chemicals interact with genes in
      known pathways in ovarian carcinogenesis and support the hypothesis that these
      chemicals are likely etiologic agents in ovarian carcinogenesis. CONCLUSION: A
      systems approach may prove useful to identify specific etiologic agents to better
      develop personalized preventive medicine strategies for those most at risk.

PMID- 24721285
TI  - [Chest tubes in ICU: another "crunch" between France and England?].

PMID- 24721286
TI  - Tuberculous pleural effusion.
AB  - Tuberculous pleural effusion (TBPE) is the most common form of extrapulmonary
      tuberculosis (TB) in Spain, and is one of the most frequent causes of pleural
      effusion. Although the incidence has steadily declined (4.8
      cases/100,000population in 2009), the percentage of TBPE remains steady with
      respect to the total number of TB cases (14.3%-19.3%). Almost two thirds are men,
      more than 60% are aged between 15-44years, and it is more common in patients with
      human immunodeficiency virus. The pathogenesis is usually a delayed
      hypersensitivity reaction. Symptoms vary depending on the population (more acute
      in young people and more prolonged in the elderly). The effusion is almost
      invariably a unilateral exudate (according to Light's criteria), more often on
      the right side, and the tuberculin test is negative in one third of cases. There
      are limitations in making a definitive diagnosis, so various pleural fluid
      biomarkers have been used for this. The combination of adenosine deaminase and
      lymphocyte percentage may be useful in this respect. Treatment is the same as for
      any TB. The addition of corticosteroids is not advisable, and chest drainage
      could help to improve symptoms more rapidly in large effusions. 

PMID- 24721287
TI  - Administration of recombinant attachment protein (r22C03) of Neoparamoeba
      perurans induces humoral immune response against the parasite in Atlantic salmon
      (Salmo salar).
AB  - This study investigated the use of a recombinant protein of Neoparamoeba
      perurans, the causative agent of Amoebic gill disease (AGD), as an immunogen to
      generate systemic and mucosal antibody responses against the parasite. Genes
      encoding N. perurans homologs of mannose-binding protein (MBP) from Acanthamoeba
      spp. have been identified. From these, a Neoparamoeba MBP - like EST has been
      identified and produced as a recombinant fusion protein. Attachment of N.
      perurans to the gill might be reduced by antibody-mediated interference of this
      protein, but this is dependent on the presence and level of functional antibodies
      in the mucus. Fish were immunized with the protein via i.p. injection with
      Freund's complete adjuvant (FCA); and serum and skin mucus samples were collected
      before and after immunization. Antibodies (IgM) present in samples were
      characterized via Western blot and their levels measured with an ELISA. The
      immunization was able to induce a systemic IgM response 8 weeks after primary
      exposure and a mucosal response 4 weeks post initial immunization, which were
      specific to the recombinant protein but not to antigens obtained from crude
      amoebic preparations. However, adherence of the antibodies to the parasite was
      observed using immunocytochemistry, and both, serum and skin mucus IgM, were able
      to bind the surface of formalin-fixed N. perurans. This finding may contribute to
      further research into the development of a vaccine for AGD. 

PMID- 24721288
TI  - Drugs and therapeutics, including contraception, for women with heart disease.
AB  - Cardiac disease remains the leading cause of maternal death in the UK, and data
      from the Centre for Maternal and Child Enquiries have shown that the numbers of
      women dying from cardiac disease have steadily increased over the past 30 years.
      The incidence of acquired heart disease is increasing because of older age at
      first pregnancy, as well as a higher prevalence of cardiovascular risk factors,
      such as hypertension, diabetes and obesity. The number of women with congenital
      heart disease who are of childbearing age is also increasing. Significant
      cardiovascular changes occur in pregnancy even from an early gestation. This can
      affect the types and doses of medications used in pregnancy. The main aims of
      management are to optimise the mother's condition during pregnancy, to monitor
      for deterioration, and to minimise any additional load on the cardiovascular
      system from pregnancy, delivery and the postpartum period. 

PMID- 24721289
TI  - The effects of food advertising and cognitive load on food choices.
AB  - BACKGROUND: Advertising has been implicated in the declining quality of the
      American diet, but much of the research has been conducted with children rather
      than adults. This study tested the effects of televised food advertising on adult
      food choice. METHODS: Participants (N = 351) were randomized into one of 4
      experimental conditions: exposure to food advertising vs. exposure to non-food
      advertising, and within each of these groups, exposure to a task that was either
      cognitively demanding or not cognitively demanding. The number of unhealthy
      snacks chosen was subsequently measured, along with total calories of the snacks
      chosen. RESULTS: Those exposed to food advertising chose 28% more unhealthy
      snacks than those exposed to non-food-advertising (95% CI: 7% - 53%), with a
      total caloric value that was 65 kcal higher (95% CI: 10-121). The effect of
      advertising was not significant among those assigned to the low-cognitive-load
      group, but was large and significant among those assigned to the high-cognitive
      load group: 43% more unhealthy snacks (95% CI: 11% - 85%) and 94 more total
      calories (95% CI: 19-169). CONCLUSIONS: Televised food advertising has strong
      effects on individual food choice, and these effects are magnified when
      individuals are cognitively occupied by other tasks.

PMID- 24721290
TI  - Impact of obesity on the effectiveness of adalimumab for the treatment of
      psoriasis: a retrospective study of 30 patients in daily practice.
AB  - BACKGROUND: The relationship between obesity and psoriasis is probably
      bidirectional. OBJECTIVES: To assess whether the effectiveness of adalimumab was
      affected by obesity in patients with psoriasis. MATERIALS & METHODS:
      Retrospective study of 30 adalimumab naive patients (13 men, 17 women, mean age
      49.5 years) with moderate to severe psoriasis. Response to treatment (PASI 50,
      75, 90, 100) was assessed over the course of six clinical visits, with a median
      between 1.9 months for visit 1 and 20.8 months for visit 6 after the start of
      adalimumab treatment. Body mass index (BMI) was categorized as normal weight
      (18.5-24.9 kg/m(2)) (n = 13), overweight (25-29.9 kg/m(2)) (n = 7), and obese
      (>30 kg/m(2)) (n = 10). RESULTS: Patients were followed for a median of 17.2
      months (minimum 2.7 months, maximum 34.4 months). The percentage of patients who
      were in complete remission (PASI 100) increased from 23.3% at visit 1 to 60% at
      visit 6. 70% of patients presented a PASI 90 response at visit 4 and this
      percentage remained unchanged at visits 5 and 6. Differences in response to
      adalimumab according to weight subgroups were not observed. The median time to
      achieve PASI 75, PASI 90 and PASI 100 responses was 20.1, 31.4 and 57.6 weeks,
      respectively. CONCLUSION: Adalimumab proved to be effective for the treatment of
      moderate to severe psoriasis in daily practice. Obesity did not appear to affect
      the efficacy of adalimumab in terms of PASI response, although patients with a
      BMI >=30 kg/m(2) discontinued treatment earlier.

PMID- 24721291
TI  - 3D - a new dimension of in vitro research.

PMID- 24721293
TI  - Improved detection of botulinum type E by rational design of a new peptide
      substrate for endopeptidase-mass spectrometry assay.
AB  - Botulinum neurotoxins (BoNTs) are the most toxic substances known to humans.
      Endopeptidase-mass spectrometry (Endopep-MS) is used as a specific and rapid in
      vitro assay to detect BoNTs. In this assay, immunocaptured toxin cleaves a
      serotype-specific peptide substrate, and the cleavage products are then detected
      by MS. To further improve the sensitivity of the assay, we report here the
      rational design of a new substrate peptide for the detection of botulinum
      neurotoxin type E (BoNT/E). Our strategy was based on previously reported
      structural interactions integrated with analysis method efficiency
      considerations. Integration of the newly designed substrate has led to a more
      than one order of magnitude increased sensitivity of the assay.

PMID- 24721292
TI  - The paradox of schizotypy: resemblance to prolonged severe mental illness in
      subjective but not objective quality of life.
AB  - An interesting paradox has emerged regarding the schizophrenia-spectrum. Put
      simply, college students with schizotypy (defined as the personality organization
      reflecting a vulnerability to schizophrenia-spectrum pathology) report
      experiencing pathology with respect to some key functional domains on a level
      that is equal to or more severe than older, outpatients with an prolonged
      psychiatric disorders. Notably, this self-reported pathology is not supported by
      objective/behavioral performance data, suggesting that the primary deficit is
      psychological in nature (e.g., metacognition). We evaluated whether this
      subjective-objective dysjunction extends to quality of life (QOL). Eighty-three
      college students with schizotypy were compared to 50 outpatients with severe
      mental illness (SMI) as well as to 82 undergraduate and 34 community control
      groups in subjective and objective QOL via a modified version of Lehman's Quality
      of Life Interview, which covers a range of QOL domains. The schizotypy and SMI
      group were equally impoverished in all measures of subjective QOL compared to the
      college and community control groups. In contrast, the schizotypy group was
      relatively normal in most measures of objective quality of life compared to the
      SMI group. The subjective-objective dysjunction appears to extend to QOL, and
      these differences do not appear to reflect a more global negativistic reporting
      bias. 

PMID- 24721294
TI  - Coordination complexes as molecular glue for immobilization of antibodies on
      cyclic olefin copolymer surfaces.
AB  - A novel metal-based chelating method has been used to provide an order of
      magnitude increase in immunoassay performance on cyclic olefin copolymer (COC)
      plastics compared with passive binding. COCs are hydrophobic, and without surface
      modification they are often unsuitable for applications where protein adhesion is
      desired. When interacting with the bare plastic, the majority of the bound
      proteins will be denatured and become nonfunctional. Many of the surface
      modification techniques reported to date require costly equipment setup or the
      use of harsh reaction conditions. Here, we have successfully demonstrated the use
      of a simple and quick metal chelation method to increase the sensitivity,
      activity, and efficiency of protein binding to COC surfaces. A detailed analysis
      of the COC surfaces after activation with the metal complexes is presented, and
      the immunoassay performance was studied using three different antibody pairs. 

PMID- 24721295
TI  - [Expecting harmonious patient-physician rapport, ending violence against medical
      professionals].

PMID- 24721296
TI  - [A retrospective comparative study of acute type A aortic dissection in patients
      with Marfan syndrome and bicuspid aortic valves].
AB  - OBJECTIVE: To compare the clinical features of type A aortic dissection (AAD) in
      patients with Marfan syndrome (MFS) and bicuspid aortic valves (BAV). METHODS:
      Data from patients undergoing surgery for acute AAD between April 2008 and April
      2012 at our institute were retrospectively collected. Patients were categorized
      into MFS group (n = 39) and BAV group (n = 28) to investigate their clinical and
      prognostic features. RESULTS: Patients in MFS and BAV groups always experienced
      the sudden onset of chest pain. MFS patients tended to have younger age [(35 +/-
      8) y vs (47 +/- 13) y, P < 0.001], wider aortic sinus [(55.4 +/- 9.8) mm vs (42.6
      +/- 8.6) mm, P < 0.01] and higher rate of moderate-to-severe aortic regurgitation
      (69.2% vs 32.1%, P = 0.003). Patients in BAV group were featured with higher rate
      of moderate-to-severe aortic stenosis. Though the operation procedures were
      similar in both groups, the 30-day postoperative mortality was significantly
      higher among BAV patients (25.0% vs 5.1%, P = 0.020). CONCLUSIONS: MFS and BAV
      represent unique subgroups of acute type A aortic dissection. BAV-associated
      dissection demonstrated strikingly higher postoperative mortality in our study
      population.

PMID- 24721297
TI  - [Clinical application of "Anatomical fixation" in the endovascular repair of
      abdominal aortic aneurysm].
AB  - OBJECTIVE: This paper aims to evaluate the clinical applyment of "Anatomical
      fixation" and its long-term efficacy . METHODS: Retrospective analysis of
      clinical data and postoperative follow-up results of 125 patients undogoing EVAR
      using "anatomical fixation" enrolled in Shanghai Changhai hospital and Shanghai
      Changzheng hospital from January 2008 to January 2013. RESULTS: The technical
      success rate was 100%, Perioperative complications including Type I endoleak
      occurred in 3 patients (2.4%), 4 cases of type II endoleak (3.2%). Incidence of
      Type I endoleak in challenging neck cases was high than non- challenging neck
      cases, the difference was statistically significant (P < 0.001). After 30 days
      and through current follow-up of 124 successful cases(mean:26.4 +/- 1.5 months,
      range 1-60 months). No rupture of the aneurysm and stent graft migrations
      occurred. Secondary type I endoleak in 2 cases (1.6%), Two cases of secondary
      type II endoleak (1.6%). Left lower extremity arterial thrombosis in 1 case
      (0.8%), and secondary surgical intervention in 1 case (0.8%). Three cases of
      deaths in cumulative, 2 patients died died of acute myocardial infarction. At 3
      months, a patient died of the contrast-induced nephropathy, renal failure.
      CONCLUSIONS: The clinical applyment of "Anatomical fixation" enriched the theory
      of EVAR, completely solved the complication of incidence of stent-graft
      migration, greatly improve the repair rate of hostile neck cases, expand the
      indications for EVAR.

PMID- 24721298
TI  - [The predictive value of plasma cystatin C for non-ST-elevation acute coronary
      syndrome treated with percutaneous coronary intervention].
AB  - OBJECTIVE: To evaluate the prognosis value of plasma cystatin C in predicting
      adverse cardiac events after percutaneous coronary intervention (PCI) for non-ST
      elevation acute coronary syndrome (NSTEACS). METHODS: A total of 277 patients
      (212 male, mean age 59 +/- 12 years) with NSTEACS underwent successful PCI. The
      patients were then divided into MACE group and non-MACE group. Patients were
      divided into 4 groups according to the level of cystatinC : Q1 (<0.78 mg/L), Q2
      (0.78-0.93 mg/L), Q3 (0.94-1.11 mg/L), and Q4 ( >= 1.12 mg/L) . Risk factors for
      MACE were analyzed by Cox regression analysis. RESULTS: The plasma Cys-C level
      were higher in MACE group than in non-MACE group(P < 0.05). The areas under ROC
      curve of Cys-C, cTnI, hsCRP an CK-MB to predict cardiac event were
      0.737,0.630,0.692 and 0.650 respectively. After a follow-up of 1 year, the MACE
      in the Q2, Q3, and Q4 groups was higher than in the Q1 group (Logrank = 23.751, P
      < 0.01). Multivariate Cox regression analysis showed that cystatin C elevation
      was an independent predictor of major adverse cardiac events (P < 0.01).
      CONCLUSION: High plasma cystatin C concentration is an independent predictor of
      major adverse cardiac events in patients with NSTEACS treated with PCI.

PMID- 24721299
TI  - [Study of side branch ostial deformation after interventional therapy of coronary
      bifurcation].
AB  - OBJECTIVE: To quantitative analyzing the deformation of SB, by using
      intravascular ultrasound (IVUS), pre and post MV stenting after cross-over
      interventional treatment by proposing a concept of "deformation index(DI)". And,
      Trying to evaluate primarily the significances of such deformation. METHODS:
      There were 53 bifurcation lesions treated by cross-over technique. All the
      diameter of side branch was >2.0 mm. Proposing the concept of DI as (MaxD
      MinD)/MaxD (MaxD, Maximum Diameter; MinD: Minimum Diameter) to present the
      morphological changes of SB ostium which was measured by IVUS. The DI will be 0
      theoretically for a regular round and tend to be a ellipse if close to 1.
      Comparison analysis the ID of SB pre and post MV stenting and try to observing
      the effective factor of it and relationship with quantitative coronary
      angiography (QAG) in coronary bifurcation intervention. RESULTS: The DI of SB
      before and after MV stenting was 0.18 +/- 0.13 and 0.26 +/- 0.16(P < 0.01)
      respectively , DI was one of correlative factors of MinD of SB ostium measured by
      QAG (CO:-0.103; P = 0.015). DI was still the independent factor with QCA- MinD of
      SB by using partial correlation analysis (P = 0.002) when other relative factors
      were controlled well. CONCLUSIONS: Ostium of SB showed a obviously ellipse trend
      after MV stenting in coronary bifurcation interventional treatment. DI was one of
      relatives of QCA-MinD of SB after procedure and may be one the causes of
      aggressive QCA-MinD of SB after interventional therapy using cross-over strategy
      in coronary bifurcation lesion.

PMID- 24721300
TI  - [Factor analysis for the prognosis of perioperative cardiopulmonary
      resuscitation].
AB  - OBJECTIVE: To provide guidance to implement effective perioperative
      cardiopulmonary resuscitation. METHODS: A total of 69 perioperative cardiac
      arrest patients who received Cardiopulmonary resuscitation according to the 2005
      guidelines in Sir Run Run Shaw Hospital from January 2005 to June 2012 were
      included (including emergency operation). According to the results of
      cardiopulmonary resuscitation, divide these 69 patients in to two groups,
      Successful resuscitation group (27cases) and failed resuscitation group
      (42cases). Compare the age, gender, ASA physical status, BMI, type of anesthesia,
      time that cardiac arrest occurred, cardiac arrest type, amount of bleeding, CPR
      duration, hypotension duration, defibrillation time, combined cardiovascular
      disease between successful resuscitation group and failed resuscitation group,
      calculate the measurement data for the chi-square test and logistic regression,
      derive factors that affect the success rate of cardiopulmonary resuscitation.
      RESULTS: A total of 69 perioperative cardiac arrest patients, according to
      Logistic regression, ASA IV-V (P = 0.029,OR = 1.956, CI = 1.226-4.809), amount of
      bleeding more than 1500 ml(P = 0.023,OR = 1.615, CI = 1.245-2.313), CPR duration
      more than 30 min(P = 0.003,OR = 3.54, CI = 3.313-5.007), hypotension duration
      more than 30 min(P = 0.002,OR = 2.782, CI = 1.791-4.322), the type of cardiac
      arrest is pulseless electrical activity(P = 0.032,OR = 1.419, CI = 0.146-1.583).
      CONCLUSION: ASA IV-V, amount of bleeding more than 1500 ml, CPR duration more
      than 30 min, hypotension duration more than 30 min and pulseless electrical
      activity are the Independent risk factors of cardiopulmonary resuscitation.

PMID- 24721301
TI  - [Natural history of scoliosis after posterior fossa decompression in patients
      with Chiari malformation/syringomyelia].
AB  - OBJECTIVE: To explore the natural history of scoliosis after posterior fossa
      decompression (PFD) in patients with Chiari malformation/syringomyelia and
      examine the risk factors associated with curve progression. METHODS: A
      retrospective radiographic study was performed at our scoliosis center for 26
      patients undergoing PFD for Chiari malformation between January 2002 and December
      2007. Their clinical and radiological parameters, including age, curve magnitude,
      curve pattern, extent of cerebellar tonsil herniation, maximal syrinx/cord ratio,
      syrinx size and length, were evaluated pre- and postoperatively. Curve
      progression was defined as an increment of Cobb angle over 5 degrees  compared
      with that of initial curve (progression group); whereas an increment of Cobb
      angle equal to or under 5 degrees  was considered curve stabilization or
      improvement (non-progression group). All aforementioned parameters at the time of
      PFD were compared between two groups with Student t and Fisher exact tests.
      RESULTS: Their average initial age, curve magnitude and follow-up duration were
      10.3 +/- 2.4 (6.5-14.7) years, 33.5 degrees  +/- 7.7 degrees  (20 degrees -45
      degrees ) and 57.5 +/- 26.9 (24-118) months respectively. At the final follow-up,
      curve improvement or stabilization occurred in 11 (42%) patients. Compared with
      the non-progression group, significantly greater initial age was observed in the
      progression group (11.1 +/- 2.2 vs 9.2 +/- 2.2 years, P = 0.041). In addition,
      the percentage of double major curve was significantly higher in the progression
      group than that in the non-progression group (26.7% vs 9.1%, P = 0.037). With
      regards to Cobb angle, Risser sign, extent of cerebellar tonsil herniation,
      maximal syrinx/cord ratio, syrinx length, sagittal parameters and percentage of
      patients with preoperative neurological signs or symptoms, no significant
      differences existed between two groups (P > 0.05). CONCLUSION: PFD may halt curve
      progression in 42% of patients with Chiari malformation/syringomyelia. And those
      with older age or double major curves are more likely to experience the
      progression of scoliosis during the post-PFD course.

PMID- 24721302
TI  - [Cognitive function in breast cancer patients on chemotherapy: a longitudinal
      study].
AB  - OBJECTIVE: To explore whether cognitive impairment in breast cancer patients
      after the completion of chemotherapy treatment in comparisons with breast cancer
      patients without chemotherapy treatment and matched healthy controls. METHODS: A
      neuropsychology battery was applied in all breast cancer patients at our hospital
      from January 2012 to February 2013. Forty-two breast cancer patients with
      chemotherapy treatment (CT) underwent neuropsychologic testing before the start
      of chemotherapy (T1) and after treatment (T2). And 37 patients without
      chemotherapy treatment (non-CT) and matched healthy controls (HC) underwent the
      same assessment at matched intervals. RESULTS: The CT group performed
      significantly worse on attention, memory and executive function tests at T2
      versus T1 (P < 0.05). As compared with HC and non-CT groups, the correct numbers
      of backward, digit symbol, delayed recall and recognition were lower in the CT
      group (P < 0.05). The reacting time of TMT test B, Stroop test B and Stroop test
      C were longer in the CT group (P < 0.05). There was significant time interaction
      in three groups (P < 0.05). CONCLUSION: There are longitudinal changes in
      cognitive functioning of memory, attention and executive functions in breast
      cancer patients on Chemotherapy.

PMID- 24721303
TI  - [Comparison of clinical symptoms for Uygur and Han Parkinson's disease patients].
AB  - OBJECTIVE: To explore the characteristics of clinical symptoms in Uygur and Han
      patients with Parkinson's disease (PD). METHODS: The unified Parkinson's disease
      rating scale (UPDRS), Hoehn-Yahr, mini-mental state examination (MMSE) scale,
      Alzheimer disease cooperative study-activities of daily living (ADCS-ADL) and
      neuropsychiatric inventory (NPI) were administered to 91 Uygur and 173 Han PD
      patients from Xinjiang Urumqi and surrounding region from June 2008 to September
      2011 to compare the characteristics of clinical symptoms between Uygur and Han
      patients. RESULTS: The subjects of drug treatment in Han [108 (62.34%)] were more
      than in Uygur [36 (39.56%), (P < 0.05)]. However there were no significant
      differences in the subjects of effective treatment between two groups (P > 0.05).
      No significant inter-group differences existed in the scores of Hoehn-Yahr (P >
      0.05). Compare with moderate and severe group in Hoehn-Yahr, there were no
      significant differences in the scores of ADL, UPDRS II and UPDRS III between two
      groups (P > 0.05). The subjects of resting tremor, increased muscle tone and
      bradykinesia as the presenting symptoms in Uygur [8 (19.05%)] were more than in
      Han [7 (7.07%), (P < 0.05)]. And the subjects of N-type progressive in Uygur [36
      (85.71%)] were more than in Han [48 (48.48%), (P < 0.05)]. There were no
      significant differences in other presenting symptoms, initial site, on-off
      phenomenon and dyskinesia between two groups (P > 0.05). No significant
      differences existed in the scores of MMSE and NPI between two groups (P > 0.05).
      CONCLUSION: No significant differences exist in typical motor symptoms, severity
      of disease, activities of daily living, cognitive dysfunction and psychiatric
      symptoms between Uygur and Han. But N-type progressive is more common in Uygur.
      And the presenting symptoms of resting tremor, increased muscle tone and
      bradykinesia are also higher in Uygur.

PMID- 24721304
TI  - [Effects of pre-pregnancy body mass index on pregnancy outcomes].
AB  - OBJECTIVE: To explore the effects of pre-pregnancy body mass index (BMI) upon
      adverse pregnancy outcomes. METHODS: We selected a population-based cohort of 48
      867 nulliparous women in mainland China with singleton and full-term deliveries
      in 2011. The cohort was categorized in accordance with pre-pregnancy BMI as
      follows: underweight <18.5; normal weight = 18.5-23.9; overweight = 24-27.9;
      obesity >= 28. Logistic regression was used to estimate the association between
      BMI and adverse maternal, peripartum and perinatal outcomes with normal weight as
      a reference range. RESULTS: (1) Overweight and obese women were more likely to
      have hypertensive disorders with odds ratios of 2.29 and 6.02, gestational
      diabetes mellitus 2.27, 4.99; (2)the odds ratios for fetal macrosomia increased
      among women with higher BMI as follows: 0.59, 1.99 and 3.15, whereas only lean
      women had significantly increased risk of delivering babies with low birth weight
      (LBW) 1.62; (3)increased BMI was associated with reduced rates of assisted
      vaginal delivery and increased rates of caesarean section. CONCLUSION: As an
      independent risk factor for adverse maternal and fetal outcomes, pre-pregnancy
      obesity should be managed properly.

PMID- 24721305
TI  - [Video endoscopic inguinal lymphadenectomy via hypogastric/limb subcutaneous
      approach for early-stage vulvar cancer].
AB  - OBJECTIVE: To describe and compare video endoscopic inguinal lymphadenectomy via
      hypogastric and limb approach (VEIL-H vs VEIL-L) in patients with invasive vulvar
      cancer. METHODS: From March 2011 to August 2013, 7 women with early-stage vulvar
      cancer were selected for this integrated procedure with a combination of VEIL-H
      and VEIL-L in bilateral groins.VEIL-L was performed on limb with old surgical
      scar in ipsilateral hypogastric area of 3 patients and VEIL-H in contralateral
      limb. Both novel procedures were performed with triple trocars respectively. The
      boundaries of inguinal lymph node dissection were the same template of open
      inguinal lymphadenectomy. Preoperative data, surgical techniques and follow-up
      outcomes were compared.Standard statistical tests were used. RESULTS: The
      combination of VEIL-H and VEIL-L was successfully completed in 7 patients without
      conversion into open surgery. The great saphenous vein was spared in 13 limbs.No
      difference existed in mean operative duration, average blood loss volume and
      median total regional lymph nodes removed in two groups. All nodes were confirmed
      tumor-free. Mean drain duration was (4.7 +/- 1.4) days in the VEIL-H group and
      (2.7 +/- 0.9) days in VEIL-L group respectively (P < 0.01). Mean drain volume was
      (123 +/- 55) ml in VEIL-H group and (62 +/- 32) ml respectively (P < 0.05). Mean
      postoperative hospital stay was (8.6 +/- 2.2) days.No major intraoperative
      complications occurred. However, hypercarbia in one patient 1 was completely
      reversible with hyperventilation.Unilateral great saphenous vein was injured in
      another one.Regarding postoperative complications, one patient suffered
      lymphocele in VEIL-H side and another had lymphorrhea through drain orifice in
      VEIL-L side. During a follow-up period of (19 +/- 7) months, there was no disease
      recurrence so far. CONCLUSION: The combination of VEIL-H and VEIL-L has the
      reproducibility and therapeutic potentials in the treatment for patients with
      vulvar cancer. Both minimal invasive techniques are viable. Although short-term
      results are encouraging, larger series with a longer follow-up are required to
      fully evaluate the therapeutic efficacy of VEIL-H and VEIL-L.

PMID- 24721306
TI  - [A multi-center retrospective study of organ involvement in adult patients with
      polymyositis or dermatomyositis].
AB  - OBJECTIVE: To explore the prevalence and characteristics of main organ
      involvement in adult patients with polymyositis (PM) or dermatomyositis (DM) and
      determine their specific relative factors. METHODS: Using unified questionnaire,
      we retrospectively collected the medical records of 1 387 confirmed adult PM/DM
      patients from 2007 to 2012 at 22 rheumatology centers in China. Statistical
      analyses were performed with chi-square or Fisher exact test and multivariate
      analyses with logistic regression. RESULTS: A total of 1 387 patients were
      collected with 460 (33.2%) PM and 927 (66.8%) DM. The female:male ratio was 2.4:
      1. Their onset age was ( 47 +/- 14) years. A total of 1 031 (74.3%) patients had
      organ involvement. The prevalence of pulmonary involvement, arthritis,
      gastrointestinal and cardiac involvement were 44.6%, 32.3%, 21.9% and 20.3%
      respectively. The multivariate analysis indicated that older onset age (P < 0.01)
      was positively associated with pulmonary involvement while myalgia (P < 0.05) was
      negatively associated. Fever (P < 0.05), weight loss (P < 0.05) and Raynaud's
      phenomenon (P < 0.01) were positively associated with arthritis while muscle
      weakness (P < 0.05) negatively associated. Weight loss (P < 0.05), Raynaud's
      phenomenon (P < 0.01) and muscle weakness (P < 0.05) were positively associated
      with gastrointestinal involvement. Weight loss (P < 0.05) and swollen limbs (P <
      0.05) were positively associated with cardiac involvement. CONCLUSION: The
      prevalence of organ involvement is high in adult PM/DM patients. Our study may
      aid the diagnosis of organ damage in PM/DM patients.

PMID- 24721307
TI  - [Establishment and validation of three dimensional finite element model of lower
      cervical bilateral facet locking].
AB  - OBJECTIVE: To establish the three dimensional finite element model of bilateral
      cervical articular process locking and verify its effectiveness. METHODS: A
      healthy adult male underwent cervical thin-layer computed tomography (CT) scan.
      The software programs of Simpleware3.0, Geomagic8.0, Hypermesh9.0, Abaqus6.9 and
      Rhino4.0 were employed to establish a complete C4, C5 segment (including
      intervertebral disc and ligament tissue) finite element model. A spring force
      load of 180 n was applied along the direction of cervical curvature. The locking
      of articular process was simulated. And its effectiveness was compared with
      previous experiments. RESULTS: Detailed anatomy structure of cervical spine was
      established. Simulated bilateral joints in journey finally formed. The load
      displacement situations and experiment results of small joint ligament were
      consistent. And shear forces and displacement differences of modeling was
      insignificant. CONCLUSION: The three dimensional finite element model of
      bilateral cervical articular process locking has excellent biological fidelity.
      And it is suitable for clinical applications.

PMID- 24721308
TI  - [Effects of gamma knife on gene expression of animal model for temporal lobe
      epilepsy in rat].
AB  - OBJECTIVE: To explore the core controlling genes and their functions and pathways
      of gamma knife in the treatment of epilepsy in rats. METHODS: The temporal
      epilepsy rats induced by stereotactic technique were irradiated with gamma knife.
      Total RNA samples were isolated at 3 weeks post-irradiation. After hybridization,
      washing and staining, the probe arrays were scanned to acquire the gene chip
      data. The functional categories and affected pathways of differentially regulated
      genes were analyzed. And the gene co-expression network was constructed to
      determine the core controlling genes. RESULTS: The differentiated genes of
      normal, epileptic and epileptic rats treated with gamma knife were screened by
      1.5-fold method. There were a total of 766 union genes. The differentiated up
      regulated and down-regulated genes were obtained. These genes were involved in
      functional categories such as ion transport (P = 6.85 * 10(-24)), cell adhesion
      (P = 1.55 * 10(-8)) , response to mechanical stimulus (P = 7.86 * 10(-7)) ,
      potassium ion transport (P = 2.63 * 10(-6)) and such pathways as MAPK signaling
      (P = 5.55 * 10(-6)), calcium signaling (P = 4.29 * 10(-5)) and TGF-beta signaling
      (P < 0.01), etc. And the core controlling genes from the gene co-expression
      network included Arf3, Akap5, Omd and Rtn4r, etc. CONCLUSION: Gamma knife
      achieves its antiepileptic effect through modulating target genes involved in
      different functions and pathways.

PMID- 24721309
TI  - [Effects of exogenous suppressor of cytokine signaling on cell apoptosis in
      ectopic endometrial stromal cells].
AB  - OBJECTIVE: To explore the effects of exogenous suppressor of cytokine signaling 3
      (SOCS3) in Janus Kinase/Signal transducer and activator of transcription 3
      (JAK2/STAT3) signaling pathways and examine the relationship between exogenous
      SOCS3 and cell proliferation and apoptosis in ectopic endometrial stromal cells.
      METHODS: Ectopic endometrial stromal cells from patients with histopathologically
      confirmed endometriosis were primarily cultured in vitro. Vimentin staining was
      used to identify the purity of endometrial stromal cells. Lentivirus containing
      SOCS3 and GFP (green fluorescent protein) recombinant (LV-SOCS3-GFP) or only GFP
      gene (LV-GFP) was used to transfect two groups of ectopic endometrial stromal
      cells from the same patient respectively. They were divided into experimental
      (EG) and negative (NC) control. The transfection efficiency of lentivirus was
      measured by GFP fluorescence expression under microscope. And the expressions of
      SOCS3, STAT3 and JAK2 mRNA and protein were analyzed by real-time polymerase
      chain reaction (PCR) and Western blot respectively. And phosphorylated JAK2 and
      STAT3 proteins (p-STAT3 and p-JAK2) were also analyzed by Western blot. Cell
      cycles and apoptosis were detected by flow cytometry. RESULTS: The transfection
      efficiency of lentivirus was over 80% at 72 h post-transfection. Compared with
      NC, EG showed a higher expression of SOCS3 mRNA (P < 0.001). SOCS3 protein level
      of EG was higher than NC while p-STAT3 protein of EG obviously lower than NC.
      STAT3, JAK2 and p-JAK2 proteins showed no difference between two groups. The
      percentage of apoptotic cells in EG was higher remarkably than NC (22.0 +/- 1.3)%
      vs (4.4 +/- 1.3)%, P < 0.01. Moreover, EG cells showed a G0/G1 arrest compared
      with NC (87.0 +/- 3.7)% vs (76.0 +/- 3.7)%, P < 0.05. CONCLUSION: Exogenous SOCS3
      induces cell apoptosis and inhibits cell proliferation in ectopic endometrial
      stromal cells.

PMID- 24721310
TI  - [Suppression of abdominal aortic aneurysm by hydrogen through chemokine-like
      factor1].
AB  - OBJECTIVE: To explore the mechanism of hydrogen on the intervention of abdominal
      aortic aneurysm (AAA). METHODS: Healthy male Sprague-Dawley rats were divided
      into AAA group and AAA intervention group (saturated hydrogen saline administered
      intraperitoneally once daily). AAA was induced by infiltration of abdominal aorta
      with 0.5 mol/L calcium chloride. Twenty-eight days later, the diameter of the
      aorta was measured, and the aortic tissue was exercised for histological
      examination. The protein location and expression of rCklf1 and matrix
      metalloproteinase 2 (MMP2) in aortic tissue were observed by immunohistochemistry
      staining. The mRNA expression of rCklf1 and MMP2 underwent real-time PCR.
      RESULTS: Dilatation rate of abdominal aorta of AAA group and AAA intervention
      group was (174 +/- 21)% and [(82 +/- 23)%, P < 0.01] respectively. The tissue
      relative mRNA expression of rCklf1 was 5.10 +/- 0.33 and 1.34 +/- 0.29 (P <
      0.01). The relative mRNA expression of MMP2 was 10.28 +/- 0.35 and 2.40 +/- 0.97
      (P < 0.01). The proteins expression of rCklf1 and MMP2 were mainly increased in
      the damaged elastic fibers of AAA group. Compared with AAA group, the AAA
      intervention group had less significant positive expression of rCklf1 and MMP2
      protein, infiltration of inflammation, destruction and degradation of elastic
      fibers. CONCLUSIONS: Hydrogen which may contribute to reduce rCklf1 expression
      prevents infiltration of inflammation and expression of MMP2 thus decreasing
      destruction and degradation of elastic fibers, therefore ameliorates development
      of AAA.

PMID- 24721311
TI  - [Prevalence and related risk factors of hypertensive patients with co-morbid
      anxiety and/or depression in community: a cross-sectional study].
AB  - OBJECTIVE: To explore the prevalence of hypertensive patients with co-morbid
      anxiety and/or depression and determine the risk factors of comorbidity in
      community. METHODS: A cross-section study was performed among 807 hypertensive
      patients in urban and rural community settings of Beijing in 2011. The Composite
      International Diagnostic Interview, computer assisted personal interview (CIDI
      3.0-CAPI) was administrated by face-to-face interview. And the diagnosis of
      anxiety and depression was made according to the definitions and criteria of
      Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DMS-IV).
      The prevalence and related risk factors of hypertensive patients with comorbid
      anxiety and/or depression were reported. RESULTS: It was found that 23.3% of
      patients were accompanied with anxiety and 5.7% with depression in hypertensive
      patients in community. The risk factors of anxiety included irregular treatment
      (odds ratio 4.500; 95% confidence interval, 2.431 to 8.331), smoking (1.805;
      1.036 to 3.145), manual labor (1.933; 1.223 to 3.053) and two or above stage of
      hypertension (1.525; 1.041 to 2.234). And the risk factors of depression included
      irregular treatment (5.333; 1.554 to 18.304), taking reserpine or ingredients
      containing reserpine (6.667; 1.981 to 22.435) and singlehood (5.000; 1.096 to
      22.820). CONCLUSION: The prevalence of anxiety is higher than depression in
      hypertensive patients in community. Irregular treatment is the common risk factor
      of anxiety and depression. Patients with smoking, manual labor and two or above
      stage of hypertension are more likely to have a coexistence of anxiety while
      those unmarried, taking reserpine or ingredients containing reserpine are more
      likely to suffer from depression.

PMID- 24721312
TI  - Review of laboratory submissions from New World camelids in England and Wales
      (2000-2011).
AB  - Sample submissions to the Animal Health and Veterinary Laboratories Agency's
      (AHVLA's) diagnostic laboratory network in England and Wales were reviewed for
      diseases affecting New World camelids (NWCs). In the years 2000-2011, 6757
      submissions were analysed, including 5154/6757 (76.3%) for diagnosing a disease
      problem and 1603/6757 (23.7%) for monitoring (no clinical disease). Wasting
      (weight loss, ill-thrift) was the most commonly reported clinical sign across all
      age groups. A diagnosis was reached for 1765/5154 (34.2%) diagnostic submissions.
      The proportion of submissions with diagnoses was higher for carcasses than non
      carcass samples and multiple diagnoses were more likely to be reached from
      carcasses. Parasitic diseases were collectively the most common problem,
      including parasitic gastroenteritis (319/1765, 18.2%), coccidiosis (187/1765,
      10.6%), fascioliasis (151/1765, 8.6%), ectoparasitic infestations (86/1765, 4.9%)
      and cryptosporidiosis (24/1765, 1.4%). The most frequently diagnosed non
      parasitic problems included nutritional diseases (182/1765, 10.3%), septicaemia
      (104/1765, 5.9%, including 45 cases of colisepticaemia), gastric ulceration
      (79/1765, 4.5%), tumours/neoplastic diseases (65/1765, 3.7%), tuberculosis
      (57/1765, 3.2%), clostridial diseases (44/1765, 2.5%), congenital anomalies
      (41/1765, 2.3%), peritonitis (39/1765, 2.2%) and Johne's disease (20/1765, 1.1%).

PMID- 24721313
TI  - Synthesis and evaluation of several oleanolic acid glycoconjugates as protein
      tyrosine phosphatase 1B inhibitors.
AB  - Sixteen novel oleanolic acid triterpenoid saponins were synthesized in an
      efficient and practical strategy, and their inhibitory activities against protein
      tyrosine phosphatase 1B (PTP1B) and selectivity over T-cell protein tyrosine
      phosphatase (TCPTP) were evaluated in vitro. The preliminary structure-activity
      relationship studies demonstrated that sugar-substituted moiety attached to the C
      3 and C-28 positions of OA scaffold greatly affected the inhibitory activity
      against PTP1B and the selectivity over TCPTP. All the compounds showed inhibitory
      potencies, and compounds 1h, 1i and 1j exhibited remarkably potent inhibitory
      activities against PTP1B with IC50 values of 1.03, 0.78 and 3.12 MUM,
      respectively. More significantly, compound 1h showed greater than 4 folds
      selectivity over highly homologous TCPTP. In parallel, the lipophilicity
      evaluation of all synthesized compounds was tested as a prediction for
      pharmacological potency. According to the predicted log P values, the predicted
      Log P results showed that lipophilicity may correlate with the evaluated
      biological potency. 

PMID- 24721314
TI  - Synthesis, crystal structures and characterization of late first row transition
      metal complexes derived from benzothiazole core: anti-tuberculosis activity and
      special emphasis on DNA binding and cleavage property.
AB  - Air and moisture stable coordination compounds of late first row transition
      metals, viz. Co(II), Ni(II), Cu(II) and Zn(II), with a newly designed ligand, 2
      (2-benzo[d]thiazol-2-yl)hydrazono)propan-1-ol (LH), were prepared and
      successfully characterized using various spectro-analytical techniques. The
      molecular structures of the ligand and nickel complex were unambiguously
      determined by single-crystal X-ray diffraction method. The [Ni(LH)2]Cl2.3H2O
      complex is stabilized by intermolecular CH?pi stacking interactions between the
      methyl hydrogen and the C18 atom of the phenyl ring (C11-H11B?C18) forming 1D zig
      zag chain structure. Both, the ligand and its copper complex, were
      electrochemically active in the working potential range, showing quasi-reversible
      redox system. The interactions of all the compounds with calf thymus DNA have
      been comprehensively investigated using electronic absorption spectroscopy,
      viscosity, electrochemistry and thermal denaturation studies. The cleavage
      reaction on pBR322 DNA has been monitored by agarose gel electrophoresis. The
      results showed that the ligand can bind to CT-DNA through partial intercalation,
      whereas the complexes bind electrostatically. Further, [Ni(LH)2]Cl2.3H2O and
      [CuLCl(H2O)2] complexes in the series have high binding and cleavage affinity
      towards pBR322 DNA. Additionally, all the compounds were screened for anti
      tuberculosis activity. All the complexes revealed an MIC value of 0.8 MUg/mL,
      which is almost 8 times active than standard used (Streptomycin, 6.25 MUg/mL). 

PMID- 24721315
TI  - Facile synthesis of benzonitrile/nicotinonitrile based s-triazines as new
      potential antimycobacterial agents.
AB  - A common strategy to synthesize 4/6-(4-(4-methylpiperazin-1-yl)-6-(4-(4-oxo-2
      phenylthiazolidin-3-yl)phenyl)-1,3,5-triazin-2
      yloxy)benzonitriles/nicotinonitriles was developed by applying an efficient
      palladium-catalyzed C-C Suzuki coupling. Moreover, the synthesized compounds were
      also tested for their in vitro antimycobacterial activity against Mycobacterium
      tuberculosis H37Rv using BACTEC MGIT and Lowenstein-Jensen MIC methods. Several
      compounds displayed profound antimycobacterial activity in combination with low
      toxicity towards mammalian cells. The best results were observed amongst the
      nicotinonitrile substituted s-triazine analogs and it could be a potential
      starting point to develop new lead compounds in the fight against M. tuberculosis
      H37Rv. The newly synthesized compounds were characterized by IR, (1)H NMR, (13)C
      NMR, MS and elemental analysis. 

PMID- 24721317
TI  - Gender-specific associations between lipids and cognitive decline in the elderly.
AB  - The aim of this study was to examine the associations between serum lipid levels
      and cognitive function in a community-based sample of non-demented subjects aged
      65 years and over. Participants were 2737 men and 4118 women from a population
      based cohort recruited from three French cities. Visual memory, verbal fluency,
      psychomotor speed, and executive abilities were evaluated at baseline, and after
      2, 4, and 7 years of follow-up. Lipid levels were evaluated at baseline.
      Multiadjusted Cox models stratified by gender were adjusted for sociodemographic
      and lifestyle characteristics, mental and physical health, and genetic
      vulnerability to dyslipidemia (apolipoprotein E and A, and cholesteryl ester
      transfer protein) and taking into account baseline vascular pathologies. In men,
      a hypercholesterolemic pattern in late-life (high total cholesterol (T-C), low
      HDL-C, high LDL-C levels) was associated with a 25 to 50% increased risk of
      decline over 7 years in psychomotor speed, executive abilities, and verbal
      fluency. Specific associations with low T-C and low LDL-C levels were also
      observed which may depend on genetic vulnerability to dyslipidemia (related to
      apolipoprotein A5 and cholesteryl exchange transfer protein). In contrast, in
      women, a 30% higher rate of decline was found in psychomotor speed with high HDL
      C levels and in executive abilities with low levels of LDL-C and triglycerides,
      in interaction with hormonal treatment. For men and women, vascular pathologies
      only slightly outweighed the risk related to lipids. This suggests a complex
      gender-specific pattern of cognitive decline involving genetic vulnerability in
      men and hormonal status in women. 

PMID- 24721316
TI  - Surface microstructure and in vitro analysis of nanostructured akermanite
      (Ca2MgSi2O7) coating on biodegradable magnesium alloy for biomedical
      applications.
AB  - Magnesium (Mg) alloys, owing to their biodegradability and good mechanical
      properties, have potential applications as biodegradable orthopedic implants.
      However, several poor properties including low corrosion resistance, mechanical
      stability and cytocompatibility have prevented their clinical application, as
      these properties may result in the sudden failure of the implants during the bone
      healing. In this research, nanostructured akermanite (Ca2MgSi2O7) powder was
      coated on the AZ91 Mg alloy through electrophoretic deposition (EPD) assisted
      micro arc oxidation (MAO) method to modify the properties of the alloy. The
      surface microstructure of coating, corrosion resistance, mechanical stability and
      cytocompatibility of the samples were characterized with different techniques
      including X-ray diffraction (XRD), scanning electron microscopy (SEM),
      transmission electron microscopy (TEM), electrochemical corrosion test, immersion
      test, compression test and cell culture test. The results showed that the
      nanostructured akermanite coating can improve the corrosion resistance,
      mechanical stability and cytocompatibility of the biodegradable Mg alloy making
      it a promising material to be used as biodegradable bone implants for orthopedic
      applications. 

PMID- 24721318
TI  - Transitions in the transcriptome of the serotonergic and dopaminergic systems in
      the human brain during adolescence.
AB  - Adolescence is a period of profound neurophysiological, behavioral, cognitive and
      psychological changes, but not much is known about the underlying molecular
      neural mechanisms. The aim of this study was to systematically analyze expression
      levels of the genes forming serotonergic and dopaminergic synapses during
      adolescence. We analyzed the mRNA expression profiles of genes that code for all
      components of serotonergic and dopaminergic synapses, in 16 brain areas from
      human and non-human primates from public domain databases, to detect genes whose
      expression changes during adolescence. Two serotonin receptors, HTR1E and HTR1B
      had expression levels that exhibit a sharp transition in the prefrontal cortex in
      adolescence, but we found no similar transition in the dopaminergic system. A
      similar but smoother rise in expression levels is observed in HTR4 and HTR5A, and
      in HTR1E and HTR1B in three other expression datasets published. An earlier rise
      is observed in HTR1A, and a smooth and significant rise with age is observed in
      the expression of HTR1E in microarray measurements in macaque monkeys. The
      expression of HTR1E and HTR1B is correlated across subjects within each age
      group, suggesting that they are controlled by common mechanisms. These results
      point to HTR1E and HTR1B as major candidate genes involved in adolescence
      maturation processes, and to their operation through common control mechanisms.
      The maturation profiles may also involve several other 5-HT receptors, including
      the genes HTR5A, HTR4 and HTR1A. 

PMID- 24721319
TI  - Involvement of mannose-binding lectin in the pathogenesis of Kawasaki disease
      like murine vasculitis.
AB  - Kawasaki disease (KD) is a paediatric idiopathic vasculitis. In this study, on
      the basis of studies using an established animal model for KD, we report that
      mannose-binding lectin (MBL) is involved in the pathogenesis of the disease. KD
      like experimental murine vasculitis was induced by intraperitoneally
      administering a Candida albicans water-soluble extract (CAWS). MBL-A gradually
      increased in the serum of the model mice treated with CAWS. Deposition of MBL-A
      and MBL-C was observed in the aortic root, including the coronary arteries, which
      is a predilection site in experimental vasculitis. Corresponding to the
      distribution patterns of MBLs, marked deposition of C3/C3-derived peptides was
      also observed. Regarding the self-reactivity of MBLs, we observed that MBLs
      interacted with core histones to activate the lectin pathway. These results
      suggest that some types of pathogens provoke the MBL-dependent complement pathway
      (lectin pathway) to cause and/or exacerbate KD-like vasculitis. 

PMID- 24721320
TI  - Reflections on renal denervation.

PMID- 24721321
TI  - Kallistatin, a novel anti-angiogenesis agent, inhibits angiogenesis via
      inhibition of the NF-kappaB signaling pathway.
AB  - Development of a novel angiogenesis inhibitor will be essential for the
      improvement of therapeutics against cancer. Kallistatin had been recognized as an
      endogenous angiogenesis inhibitor. Here, we demonstrated kallistatin's strong
      anti-angiogenesis and anti-metastasis activity stimulated by breast cancer cells
      (MCF-7) and its mechanism of action in vitro. The anti-angiogenesis effect in
      vivo was evaluated by chicken chorioallantoic membrane (CAM) neovascularisation.
      Because of the underlying molecular mechanism of its anti-angiogenesis activity
      remains poorly understood. In this study, we examined whether the NF-kappaB
      signaling pathway was involved in the anti-angiogenesis and anti-metastasis
      activity of kallistatin. Kallistatin significantly inhibited TNF-alpha-induced
      nuclear factor-kappaB activation in a dose-dependent manner. Addition of
      kallistatin inhibited TNF-alpha induced IkappaBalpha degradation; phosphorylation
      of IkappaBalpha kinase (IKK), nuclear factor-kappaB-p65 protein; and nuclear
      translocation of p65/50. Meanwhile, we investigated the effects of kallistatin on
      the expression of vascular endothelial growth factor (VEGF) and other
      angiogenesis-related gene in human umbilical vein endothelial cells (HUVECs). We
      found that kallistatin decreased the expression of VEGF and some angiogenesis
      related genes, which promoted angiogenesis in cancer. Taken together, we
      suggested that kallistatin would inhibit tumor angiogenesis via inhibition of the
      NF-kappaB signaling pathway and finally abrogate NF-kappaB-dependent gene
      expression. All the results revealed that kallistatin would have potential as a
      novel. 

PMID- 24721322
TI  - The role of BRAF(V600E) mutation as poor prognostic factor for the outcome of
      patients with intrathyroid papillary thyroid carcinoma.
AB  - BACKGROUND: BRAF(V600E) mutation, which represents the most frequent genetic
      mutation in papillary thyroid carcinoma (PTC), is widely considered to have an
      adverse outcome on PTC outcome, however its real predictive value is not still
      well stated. The aim of the present study was to evaluate if BRAF(V600E) mutation
      could be useful to identify within patients with intrathyroid ultrasound-N0 PTC
      those who require more aggressive treatment, by central neck node dissection
      (CLND) or subsequent postoperative (131)I treatment. METHODS: Among the whole
      series of 931 consecutive PTC patients operated on at 2nd Clinical Surgery of
      University of Padova and at General Surgery Department of University of Trieste
      during a period from January 2007 to December 2012, we selected 226 patients with
      an intrathyroid tumor and no metastases (preoperative staging T1-T2, N0, M0).
      BRAF(V600E) mutation was evaluated by PCR-single-strand conformation polymorphism
      analysis and direct genomic sequencing. We analyzed the correlation between the
      presence/absence of the BRAF(V600E) mutation in the fine-needle aspiration (FNA)
      and the clinical-pathological features: age, gender, extension of surgery, node
      dissection, rate of cervical lymph node involvement, tumor size, TNM stage,
      variant of histotype, mono/plurifocality, association with lymphocitary chronic
      thyroiditis, radioactive iodine ablation doses, and outcome. RESULTS: The
      BRAF(V600E) mutation was present in 104 of 226 PTC patients (47.8%). BRAF(V600E)
      mutation correlated with multifocality, more aggressive variants, infiltration of
      the tumoral capsule, and greater tumor's diameter. BRAF(V600E) mutation was the
      only poor prognostic factor in these patients. DISCUSSION: In our series,
      BRAF(V600E) mutation demonstrated to be an adverse prognostic factor indicating
      aggressiveness of disease and it could be useful in the management of low-risk
      PTC patients, as supplementary prognostic factor to assess the preoperative risk
      stratification with the aim to avoid unnecessary central neck node dissection
      (BRAF pos.) or to perform complementary (131)I-therapy (BFAF neg.).

PMID- 24721323
TI  - Non-toxic dose chidamide synergistically enhances platinum-induced DNA damage
      responses and apoptosis in Non-Small-Cell lung cancer cells.
AB  - Combination of low doses of histone deacetylases inhibitors and chemotherapy
      drugs is considered as one of the most promising strategies to increase the
      anticancer efficacy. Chidamide is a novel benzamide chemical class of HDAC
      inhibitor that selectively inhibited HDAC1, 2, 3 and 10. We sought to determine
      whether chidamide may enhance platinum-induced cytotoxicity in NSCLC cells. In
      this study, the combination of chidamide with carboplatin showed a good synergism
      on growth inhibition with the mean combination index value as 0.712 and 0.639 in
      A549 and NCI-H157 cells, respectively. The used concentration of chidamide was
      non-toxic on cells by itself as low as 0.3MUM. All of our experiments were
      comparisons between combination regimen and single carboplatin regimen in A549
      and NCI-H157 cell lines. Phosphorylated histone H2A.X (gammaH2A.X), a hall marker
      of DNA damage response, was dramatically increased by the combination treatment.
      Cell cycle analysis by flow cytometry and phosphorylation level analysis of
      histone H3 (Ser10) by western blotting showed that combination treatment
      significantly increased the percentage of G2/M phase of cells. Mitochondrial
      membrane potential and cleaved-PARP1 level analysis indicate that chidamide
      synergistically enhances carboplatin-induced apoptosis. Additionally, synergistic
      effects of chidamide were found when it was combined with two other platinum
      drugs (cisplatin and oxaliplatin). The results suggest that Chidamide in
      combination with platinum drugs may be a novel therapeutic option for NSCLC. 

PMID- 24721324
TI  - Piroxicam and c-phycocyanin prevent colon carcinogenesis by inhibition of
      membrane fluidity and canonical Wnt/beta-catenin signaling while up-regulating
      ligand dependent transcription factor PPARgamma.
AB  - The colon cancer tissues from DMH treated rats exhibited higher membrane
      potential, fluidity and changed lipid order as examined by Merocyanine 540 and
      1,6-diphenyl-1,3,5-hexatriene, respectively. A transition from gel to liquid
      crystalline state was observed by Laurdan fluorescence and also reduced
      fluorescence quenching of NBD-PE as contributed in the decreased membrane lipid
      phase separation. With piroxicam, a traditional NSAID and c-phycocyanin, a
      biliprotein from Spirulina platensis, these effects were normalized. An augmented
      intracellular Ca(+2) had contributed to the drug mediated apoptosis which is
      supported by an elevated calpain-9 expression. Histopathologically, a large pool
      of secreted acid/neutral mucopolysaccrides as well as the presence of blood
      vessels and dysplastic crypts signifies invasive mucinous adenocarcinoma while
      both the drugs reduced these neoplastic alterations. Wnt/beta-catenin pathway was
      also found to be up-regulated which served as a crucial indicator for cancer cell
      growth. A concomitant down regulation of PPARgamma was noted in DMH treatment
      which is associated with tumor progression. The expression of PPARalpha and
      delta, the other two isoforms of PPAR family was also modulated. We conclude that
      piroxicam and c-phycocyanin exert their anti-neoplastic effects via regulating
      membrane properties, raising calpain-9 and PPARgamma expression while suppressing
      Wnt/beta-catenin signaling in experimental colon carcinogenesis. 

PMID- 24721325
TI  - Enhanced expression of long non-coding RNA ZXF1 promoted the invasion and
      metastasis in lung adenocarcinoma.
AB  - The identification of cancer-associated long non-coding RNAs (LncRNA) and the
      investigation of their molecular and biological functions are important for
      understanding the molecular biology and progression of cancer. This study aims to
      find the key LncRNA associated with lung adenocarcinoma and to evaluate its
      biological role and clinical significance in tumor progression. Microarray
      analysis of 32,756 LncRNA was performed to screen the significantly different
      LncRNA between human lung adenocarcinoma tissues and adjacent non-cancerous lung
      tissues, which was named as LncRNA ZXF1. Expression of LncRNA ZXF1 was analyzed
      in 62 lung adenocarcinoma tissues and adjacent non-cancerous lung tissues by
      quantitative reverse-transcription PCR (qRT-PCR). Correlations between LncRNA
      ZXF1 expression and the clinicopathological features and prognosis of patients
      were also analyzed. The inhibition of LncRNA ZXF1 using siRNA treatment was
      performed in order to explore its role in tumor progression. The effect of LncRNA
      ZXF1 on proliferation was evaluated by CCK-8 assay using A549 cell lines, and
      cell migration and invasion were detected by transwell assays. Here we found that
      LncRNA ZXF1 levels were remarkably increased in lung adenocarcinoma tissues
      compared with adjacent non-cancerous lung tissues (P<0.05), and up-regulated
      LncRNA ZXF1 was correlated with lymph node metastasis (P<0.05), tumor
      pathological stage (P<0.05) and the extent of lymph node metastasis (correlation
      coefficient=0.366). The 3-year overall survival rate of patients with higher
      LncRNA ZXF1 levels was remarkably reduced compared with patients with lower
      LncRNA ZXF1 levels, implying that patients with high levels of LncRNA
      ZXF1expression had a relatively poor prognosis. Inhibition of LncRNA ZXF1 by
      siRNA decreased the migration and invasion of A549 cells in vitro, while there
      was no significant effect in cell proliferation. 

PMID- 24721326
TI  - Basal proteinuria as a prognostic factor in patients with metastatic colorectal
      cancer treated with bevacizumab.
AB  - BACKGROUND: The beneficial effects of bevacizumab, a widely used agent in
      metastatic colorectal cancer (mCRC), on clinical survival have been proven. This
      study investigated the correlation of the clinical benefits and prognosis with
      proteinuria and other parameters. METHODS: The study included mCRC patients
      receiving bevacizumab. Hypertension, 24-hour urine proteinuria, and other routine
      parameters were recorded at baseline and at certain intervals during treatment.
      RESULTS: The study included 36 consecutive patients. The median progression-free
      survival (PFS) duration was 10.9+/-2.6months, and the median overall survival
      (OS) was 23+/-3.1months. The median PFS was 7.2months among patients with basal
      proteinuria above 114mg/day, whereas the median PFS was 12months among patients
      with an equal or lower level (P=0.010). Similarly, PFS was shorter in patients
      with high lactate dehydrogenase (LDH) or carcinoembryonic antigen (CEA) levels
      (LDH, P=0.022; CEA, P=0.014). Bevacizumab response's performance status was good
      (P=0.05) and was even better in patients with a single liver metastasis (P=0.034)
      or hypertension (P=0.034). CONCLUSIONS: We demonstrated that high basal
      proteinuria, LDH, or CEA levels may be negative prognostic factors in mCRC
      patients receiving bevacizumab.

PMID- 24721327
TI  - Tamoxifen guided liposomes for targeting encapsulated anticancer agent to
      estrogen receptor positive breast cancer cells: in vitro and in vivo evaluation.
AB  - Tamoxifen (TMX), an estrogen receptor (ER) antagonist, incorporated at surface of
      liposomes loaded with Doxorubicin (DOX), was hypothesized to serve as ligand for
      targeting overexpressed ERs on surface and cytosol of breast cancer cells, in
      addition to its synergism with DOX in killing MCF-7 cells. The TMX-DOX liposomes
      demonstrated mean size of 188.8+/-2.2nm and positive potential of+47mV, both
      suitable for better cellular interaction. TMX-DOX liposomes sustained DOX release
      in vitro (25.9%) in pH 7.4 at 48h, in comparison with 64.5% DOX release at pH
      5.5. In vitro cell line studies demonstrated that TMX-DOX liposomes were more
      cytotoxic to ER+ve MCF-7 cells as compared to DOX liposomes, DOX solution and TMX
      DOX solution (P<0.05). However, there was no statistical difference in cyto
      toxicity of TMX-DOX liposomes and DOX liposomes towards ER-ve MDA-MB-231 cells.
      Flow cytometry and confocal studies in MCF-7 cells revealed greater cell and
      nuclear uptake of DOX, with TMX guided liposomes as compared to DOX liposomes and
      DOX solution. TMX-DOX liposomes demonstrated significantly increased inhibition
      of MCF-7 cell based tumor growth in nude mice (P<0.05) in comparison to DOX
      solution and DOX liposomes, indicative of target specificity and higher DOX
      accumulation at tumor site. 

PMID- 24721328
TI  - RY10-4 suppressed metastasis of MDA-MB-231 by stabilizing ECM and E-cadherin.
AB  - In the article, we investigated the anti-metastasis mechanism of RY10-4, an anti
      tumor compound derived from protoapigenone, in breast tumor cells MB-MDA-231. The
      analog of protoapigenone with an unaromatic B-ring was verified to suppress the
      proliferation of several tumor cells by previous research that also showed that
      several tumor progression such as inducing apoptosis and anti-angiogenesis could
      be acted on by RY10-4. In the article, we investigated the mechanism about how
      RY10-4 suppressed the invasion of MDA-MB-231. Firstly, the transwells assays with
      and without matrigel were adapted to evaluate the anti-metastasis and anti
      invasion activity. Much research had demonstrated that the ECM and E
      cadherin/beta-catenin complex play an important role in cell adhesion and the
      formation of the cell skeleton, and as we knew the abnormal and absent expression
      of ECM and E-cadherin/beta-catenin complex are found in many malignant cells. The
      result demonstrated that the amount and distribution of E-cadherin/beta-catenin
      complex were backed on track by RY10-4, and the expression of MMP-2/9 in MDA-MB
      231, which functions as a major negative factor of ECM, was down-regulated after
      co-cultured with RY10-4. Furthermore the pathway related to MMP-2/9 and E
      cadherin was assessed by the western blot. As the results showed, the MAPK
      pathway and the spread of beta-catenin were affected by RY10-4 to exert the anti
      metastasis on MDA-MB-231. Collectively, the research revealed a novel anti-tumor
      ability of RY10-4 by inhibiting migration and invasion in MDA-MB-231. 

PMID- 24721329
TI  - Supra-vesical hernia presenting as intestinal obstruction.
AB  - Supra-vesical hernia is a rare form of internal hernia. It often presents as
      bowel obstruction. Diagnosis is increasingly established pre-operatively because
      of the broader application of computed tomography in cases of intestinal
      obstruction. 

PMID- 24721330
TI  - Fundamentals of robotic surgery or of robotic-assisted telemanipulated
      laparoscopy.

PMID- 24721331
TI  - Finding brain oscillations with power dependencies in neuroimaging data.
AB  - Phase synchronization among neuronal oscillations within the same frequency band
      has been hypothesized to be a major mechanism for communication between different
      brain areas. On the other hand, cross-frequency communications are more flexible
      allowing interactions between oscillations with different frequencies. Among such
      cross-frequency interactions amplitude-to-amplitude interactions are of a special
      interest as they show how the strength of spatial synchronization in different
      neuronal populations relates to each other during a given task. While,
      previously, amplitude-to-amplitude correlations were studied primarily on the
      sensor level, we present a source separation approach using spatial filters which
      maximize the correlation between the envelopes of brain oscillations recorded
      with electro-/magnetoencephalography (EEG/MEG) or intracranial multichannel
      recordings. Our approach, which is called canonical source power correlation
      analysis (cSPoC), is thereby capable of extracting genuine brain oscillations
      solely based on their assumed coupling behavior even when the signal-to-noise
      ratio of the signals is low. In addition to using cSPoC for the analysis of cross
      frequency interactions in the same subject, we show that it can also be utilized
      for studying amplitude dynamics of neuronal oscillations across subjects. We
      assess the performance of cSPoC in simulations as well as in three distinctively
      different analysis scenarios of real EEG data, each involving several subjects.
      In the simulations, cSPoC outperforms unsupervised state-of-the-art approaches.
      In the analysis of real EEG recordings, we demonstrate excellent unsupervised
      discovery of meaningful power-to-power couplings, within as well as across
      subjects and frequency bands. 

PMID- 24721332
TI  - Mapping tissue sodium concentration in the human brain: a comparison of MR
      sequences at 9.4Tesla.
AB  - Sodium is the second most abundant MR-active nucleus in the human body and is of
      fundamental importance for the function of cells. Previous studies have shown
      that many pathophysiological conditions induce an increase of the average tissue
      sodium concentration. To date, several MR sequences have been used to measure
      sodium. The aim of this study was to evaluate the performance and suitability of
      five different MR sequences for quantitative sodium imaging on a whole-body
      9.4Tesla MR scanner. Numerical simulations, phantom experiments and in vivo
      imaging on healthy subjects were carried out. The results demonstrate that, of
      these five sequences, the Twisted Projection Imaging sequence is optimal for
      quantitative sodium imaging, as it combines a number of features which are
      particularly relevant in order to obtain high quality quantitative images of
      sodium. These include: ultra-short echo times, efficient k-space sampling, and
      robustness against off-resonance effects. Mapping of sodium in the human brain is
      a technique not yet fully explored in neuroscience. Ultra-high field sodium MRI
      may provide new insights into the pathogenesis of neurological disorders, and may
      help to develop new and disease-specific biomarkers for the early diagnosis and
      therapeutic intervention before irreversible brain damage has taken place. 

PMID- 24721333
TI  - Supervised DNA Barcodes species classification: analysis, comparisons and
      results.
AB  - BACKGROUND: Specific fragments, coming from short portions of DNA (e.g.,
      mitochondrial, nuclear, and plastid sequences), have been defined as DNA Barcode
      and can be used as markers for organisms of the main life kingdoms. Species
      classification with DNA Barcode sequences has been proven effective on different
      organisms. Indeed, specific gene regions have been identified as Barcode: COI in
      animals, rbcL and matK in plants, and ITS in fungi. The classification problem
      assigns an unknown specimen to a known species by analyzing its Barcode. This
      task has to be supported with reliable methods and algorithms. METHODS: In this
      work the efficacy of supervised machine learning methods to classify species with
      DNA Barcode sequences is shown. The Weka software suite, which includes a
      collection of supervised classification methods, is adopted to address the task
      of DNA Barcode analysis. Classifier families are tested on synthetic and
      empirical datasets belonging to the animal, fungus, and plant kingdoms. In
      particular, the function-based method Support Vector Machines (SVM), the rule
      based RIPPER, the decision tree C4.5, and the Naive Bayes method are considered.
      Additionally, the classification results are compared with respect to ad-hoc and
      well-established DNA Barcode classification methods. RESULTS: A software that
      converts the DNA Barcode FASTA sequences to the Weka format is released, to adapt
      different input formats and to allow the execution of the classification
      procedure. The analysis of results on synthetic and real datasets shows that SVM
      and Naive Bayes outperform on average the other considered classifiers, although
      they do not provide a human interpretable classification model. Rule-based
      methods have slightly inferior classification performances, but deliver the
      species specific positions and nucleotide assignments. On synthetic data the
      supervised machine learning methods obtain superior classification performances
      with respect to the traditional DNA Barcode classification methods. On empirical
      data their classification performances are at a comparable level to the other
      methods. CONCLUSIONS: The classification analysis shows that supervised machine
      learning methods are promising candidates for handling with success the DNA
      Barcoding species classification problem, obtaining excellent performances. To
      conclude, a powerful tool to perform species identification is now available to
      the DNA Barcoding community.

PMID- 24721334
TI  - Pilot randomized controlled trial of self-regulation in promoting function in
      acute poststroke patients.
AB  - OBJECTIVE: To test the efficacy of self-regulation (SR) for promoting task
      performance and motor and cognitive functions. DESIGN: Pilot randomized
      controlled trial. SETTING: Rehabilitation unit. PARTICIPANTS: Inpatients with
      acute poststroke (N=44) after a cerebral infarction aged >=60 years.
      INTERVENTIONS: Patients were randomly assigned to the SR (n=24) or functional
      rehabilitation (control; n=20) intervention. The SR intervention consisted of 1
      week of therapist-supervised practices of daily tasks using SR of one's own
      performance (five 1-h sessions). Patients in the control intervention practiced
      the same daily tasks with a therapist's demonstration and guidance. MAIN OUTCOME
      MEASURES: Performance of tasks, including household and monetary transaction
      tasks; FIM; Fugl-Meyer Assessment (FMA); and Color Trails Test (CTT). RESULTS:
      The SR group showed significant improvement in all tasks (median difference, 1-2;
      effect size [r]=.74-.89) versus none (median difference, 0-0.5) in the control
      group. Results of the FIM (P<.001, r=.87 in the motor subscale; P<.001, r=.49 in
      the cognitive subscale), FMA (P<.001, r=.84 for upper extremity motor function
      and r=.63 for lower extremity motor function), and CTT (P=.002, r=.72) of the SR
      group improved. The SR group outperformed their control counterparts in 4 of the
      5 tasks (median difference, 1; r=.30-.52) and in the FIM motor subscale (P=.002,
      r=.47), but not in the cognitive subscale and motor and cognitive functions.
      CONCLUSIONS: SR appears useful for improving task performance that demands both
      motor and cognitive abilities by promoting information processing and active
      learning.

PMID- 24721335
TI  - Three new players in energy regulation: preptin, adropin and irisin.
AB  - Homeostasis of energy is regulated by genetic factors, food intake, and energy
      expenditure. When energy input is greater than expenditure, the balance is
      positive, which can lead to weight gain and obesity. When the balance is
      negative, weight is lost. Regulation of this homeostasis is multi-factorial,
      involving many orexigenic (appetite-stimulating) and anorexigenic (appetite
      suppressing) peptide hormones. Peripheral tissues are now known to be involved in
      weight regulation and research on its endocrine characteristics proceeds apace.
      Preptin with 34 amino acids (MW 3948 Da), adropin with 43 amino acids and a
      molecular weight of (4999 Da), and irisin with 112 amino acids (12587 Da), are
      three newly discovered peptides critical for regulating energy metabolism.
      Preptin is synthesized primarily in pancreatic beta cells, and adropin mainly in
      the liver and brain, and many peripheral tissues. Irisin, however, is synthesized
      principally in the heart muscle, along with peripheral tissues, including
      salivary glands, kidney and liver. The prime functions of preptin and adropin
      include regulating carbohydrate, lipid and protein metabolisms by moderating
      glucose-mediated insulin release. Irisin is an anti-obesitic and anti-diabetic
      hormone regulating adipose tissue metabolism and glucose homeostasis by
      converting white to brown adipose tissue. This review offers a historical account
      of these discovery and function of these peptides, including their structure, and
      physiological and biochemical properties. Their roles in energy regulation will
      be discussed. Their measurement in biological fluids will be considered, which
      will lead to further discussion of their possible clinical value.

PMID- 24721337
TI  - Corticosterone, food intake and refueling in a long-distance migrant.
AB  - Elevated baseline corticosterone levels function to mobilize energy in
      predictable life-history stages, such as bird migration. At the same time,
      baseline corticosterone has a permissive effect on the accumulation of fat stores
      (fueling) needed for migratory flight. Most migrants alternate flight bouts with
      stopovers, during which they replenish the fuel used during the preceding flight
      (refueling). The role of corticosterone in refueling is currently unclear. In a
      fasting-re-feeding experiment on northern wheatears (Oenanthe oenanthe) in autumn
      we found that baseline total and free corticosterone levels were negatively
      related with both food intake and the rate of fuel deposition after fasting. This
      confirms our earlier findings in wild conspecifics in spring and indicates that
      corticosterone does not stimulate stopover refueling. Whether the negative
      relationship between baseline corticosterone level and fuel deposition rate is
      causal is questionable, because within-individual comparison of corticosterone
      metabolite levels in droppings did not reveal differences between refueling and
      control periods. In other words, corticosterone does not appear to be down
      regulated during refueling, which would be expected if it directly hampers
      refueling. We discuss possible correlates of corticosterone level that may
      explain the negative association between corticosterone and stopover refueling.
      Additionally, we found that fasting decreases total corticosterone level, which
      contrasts with previous studies. We propose that the difference is due to the
      other studies being conducted outside of the migration life-history stage, and
      provide a possible explanation for the decrease in corticosterone during fasting
      in migrating birds. 

PMID- 24721336
TI  - Appetite regulating peptides in red-bellied piranha, Pygocentrus nattereri:
      cloning, tissue distribution and effect of fasting on mRNA expression levels.
AB  - cDNAs encoding the appetite regulating peptides apelin, cocaine and amphetamine
      regulated transcript (CART), cholecystokinin (CCK), peptide YY (PYY) and orexin
      were isolated in red-bellied piranha and their mRNA tissue and brain
      distributions examined. When compared to other fish, the sequences obtained for
      all peptides were most similar to that of other Characiforme fish, as well as to
      Cypriniformes. All peptides were widely expressed within the brain and in several
      peripheral tissues, including gastrointestinal tract. In order to assess the role
      of these peptides in the regulation of feeding of red-bellied piranha, we
      compared the brain mRNA expression levels of these peptides, as well as the gut
      mRNA expression of CCK and PYY, between fed and 7-day fasted fish. Within the
      brain, fasting induced a significant increase in both apelin and orexin mRNA
      expressions and a decrease in CART mRNA expression, but there where were no
      significant differences for either PYY or CCK brain mRNA expressions between fed
      and fasted fish. Within the intestine, PYY mRNA expression was lower in fasted
      fish compared to fed fish but there was no significant difference for CCK
      intestine mRNA expression between fed and fasted fish. Our results suggest that
      these peptides, perhaps with the exception of CCK, play a major role in the
      regulation of feeding of red-bellied piranha. 

PMID- 24721338
TI  - Perceptions of quality of life among Ugandan patients living with HIV: a
      qualitative study.
AB  - BACKGROUND: Ugandans have endured the HIV epidemic for three decades. Now, with
      the availability of antiretroviral therapy (ART) and early diagnosis, those
      living with HIV can live longer and can enjoy the same life expectancy as the
      rest of the Ugandan population. This emerging trend necessitates the assessment
      of quality of life, alongside other patient outcomes, of those undergoing
      therapy, alongside other patient outcomes. While major strides have been made in
      developing measures of quality of life in the developed world, there remains a
      paucity of evidence from resource-limited settings. This challenge is further
      complicated by the contentious definition of quality of life, which is highly
      subjective and varies between individuals. In this paper, we aim to identify the
      determinants of quality of life for people living with HIV in a Ugandan context
      to contribute to the chronic care model for persons living with HIV/AIDS.
      METHODS: Twenty HIV-positive participants took part in in-depth interviews at an
      urban clinic, with follow-ups at three and six months. Ten patients were on ART
      and ten not on ART. All interviews were transcribed and translated for analysis.
      Data were analysed manually using the framework approach to content analysis.
      RESULTS: Individuals reported on four aspects of quality of life: liveability of
      the environment, utility of life, life ability of a person and appreciation of
      life. Respondents described multiple expectations and expressed hope for their
      future. However, many still suffered from stigma, fears of disclosure and
      poverty, which negatively affected their quality of life. CONCLUSIONS:
      Individuals living with HIV receiving treatment or in care experienced an
      improved quality of life in this setting, although the situation for many remains
      precarious.

PMID- 24721339
TI  - Body-mass index and mortality in incident dementia: a cohort study on 11,398
      patients from SveDem, the Swedish Dementia Registry.
AB  - BACKGROUND: Body mass index (BMI) is used worldwide as an indirect measure of
      nutritional status and has been shown to be associated with mortality.
      Controversy exists over the cut points associated with lowest mortality,
      particularly in older populations. In patients suffering from dementia,
      information on BMI and mortality could improve decisions about patient care.
      OBJECTIVES: The objective was to explore the association between BMI and
      mortality risk in an incident dementia cohort. DESIGN: Cohort study based on
      SveDem, the Swedish Quality Dementia Registry; 2008-2011. SETTING: Specialist
      memory clinics, Sweden. PARTICIPANTS: A total of 11,398 patients with incident
      dementia with data on BMI (28,190 person-years at risk for death). MAIN OUTCOME
      MEASURES: Hazard ratios and 95% confidence intervals for mortality associated
      with BMI were calculated, controlling for age, sex, dementia type, results from
      Mini-Mental State Examination, and number of medications. BMI categories and
      linear splines were used. RESULTS: Higher BMI was associated with decreased
      mortality risk, with all higher BMI categories showing reduced risk relative to
      patients with BMI of 18.5 to 22.9 kg/m(2), whereas underweight patients (BMI
      <18.5 kg/m(2)) displayed excess risk. When explored as splines, increasing BMI
      was associated with decreased mortality risk up to BMI of 30.0 kg/m(2). Each
      point increase in BMI resulted in an 11% mortality risk reduction in patients
      with BMI less than 22.0 kg/m(2), 5% reduction when BMI was 22.0 to 24.9 kg/m(2),
      and 3% risk reduction among overweight patients. Results were not significant in
      the obese weight range. Separate examination by sex revealed a reduction in
      mortality with increased BMI up to BMI 29.9 kg/m(2) for men and 24.9 kg/m(2) for
      women. CONCLUSION: Higher BMI at the time of dementia diagnosis was associated
      with a reduction in mortality risk up to and including the overweight category
      for the whole cohort and for men, and up to the normal weight category for women.

PMID- 24721340
TI  - Letter referring to the article "development and testing of a decision aid on
      goals of care for advanced dementia" by Einterz et al.

PMID- 24721341
TI  - New toolkit to measure quality of person-centered care: development and pilot
      evaluation with nursing home communities.
AB  - BACKGROUND: Increasingly, nursing home (NH) providers are adopting a person
      centered care (PCC) philosophy; yet, they currently lack methods to measure their
      progress toward this goal. Few PCC tools meet criteria for ease of use and
      feasibility in NHs. The purpose of this article is to report on the development
      of the concept and measurement of preference congruence among NH residents (phase
      1), its refinement into a set of quality indicators by Advancing Excellence in
      America's Nursing Homes (phase 2), and its pilot evaluation in a sample of 12
      early adopting NHs prior to national rollout (phase 3). The recommended toolkit
      for providers to use to measure PCC consists of (1) interview materials for 16
      personal care and activity preferences from Minimum Data Set 3.0, plus follow-up
      questions that ask residents how satisfied they are with fulfillment of important
      preferences; and (2) an easy to use Excel spreadsheet that calculates graphic
      displays of quality measures of preference congruence and care conference
      attendance for an individual, household or NH. Twelve NHs interviewed residents
      (N = 146) using the toolkit; 10 also completed a follow-up survey and 9 took part
      in an interview evaluating their experience. RESULTS: NH staff gave strong
      positive ratings to the toolkit. All would recommend it to other NHs. Staff
      reported that the toolkit helped them identify opportunities to improve PCC
      (100%), and found that the Excel tool was comprehensive (100%), easy to use
      (90%), and provided high quality information (100%). Providers anticipated using
      the toolkit to strengthen staff training as well as to enhance care planning,
      programming and quality improvement. CONCLUSIONS: The no-cost PCC toolkit
      provides a new means to measure the quality of PCC delivery. As of February 2014,
      over 700 nursing homes have selected the Advancing Excellence in America's
      Nursing Homes PCC goal as a focus for quality improvement. The toolkit enables
      providers to incorporate quality improvement by moving beyond anecdote, and
      advancing more systematically toward honoring resident preferences.

PMID- 24721343
TI  - [Diagnosis and treatment of pancreatic cystic neoplasms].

PMID- 24721342
TI  - A novel mutation in the SLC25A15 gene in a Turkish patient with HHH syndrome:
      functional analysis of the mutant protein.
AB  - The hyperornithinemia-hyperammonemia-homocitrullinuria syndrome is a rare
      autosomal recessive disorder caused by the functional deficiency of the
      mitochondrial ornithine transporter 1 (ORC1). ORC1 is encoded by the SLC25A15
      gene and catalyzes the transport of cytosolic ornithine into mitochondria in
      exchange for citrulline. Although the age of onset and the severity of the
      symptoms vary widely, the disease usually manifests in early infancy. The typical
      clinical features include protein intolerance, lethargy, episodic confusion,
      cerebellar ataxia, seizures and mental retardation. In this study, we identified
      a novel p.Ala15Val (c.44C>T) mutation by genomic DNA sequencing in a Turkish
      child presenting severe tantrum, confusion, gait disturbances and loss of speech
      abilities in addition to hyperornithinemia, hyperammonemia and homocitrullinuria.
      One hundred Turkish control chromosomes did not possess this variant. The
      functional effect of the novel mutation was assessed by both complementation of
      the yeast ORT1 null mutant and transport assays. Our study demonstrates that the
      A15V mutation dramatically interferes with the transport properties of ORC1 since
      it was shown to inhibit ornithine transport nearly completely. 

PMID- 24721344
TI  - [Strategies of developing translational research on cancer prevention and control
      in China].

PMID- 24721345
TI  - [Down-regulated expression of PP2A catalytic subunit in pancreatic cancer cells
      promotes cell growth].
AB  - OBJECTIVE: To investigate the expression of protein phosphatase 2A catalytic
      subunit (PP2Ac) in pancreatic cancer and the regulation of this gene on JNK/c
      Jun/AP-1 pathway and cell growth. METHODS: Expression of PP2Ac was determined by
      real-time PCR. Cell viability was tested by MTT.Expression and phosphorylation
      levels of proteins were detected by Western blotting. Cell cycle was assayed by
      flow cytometry. Transcription activity was measured by luciferase reporter gene
      assay. RESULTS: Suppressed PP2Ac expression was detected in pancreatic cancer
      tissues. PP2Ac expression in the pancreatic cancer cell lines was also at a low
      level.Overexpression of the two isoforms of PP2Ac, PP2Acalpha and PP2Acbeta, in
      pancreatic cancer cells repressed cell growth. Cell viability decreased (33.89 +/
      2.05)% (t = 28.607, P < 0.001) and (16.66 +/- 2.81)% (t = 10.257, P = 0.001)
      respectively 72 hours after transfection.Overexpression of PP2Acalpha and
      PP2Acbeta down-regulated the phosphorylation levels of JNK and c-Jun, and made
      the transcriptional activity of AP-1 decrease (47.18 +/- 2.28)% (t = 11.230, P <
      0.001) and (30.89 +/- 8.09)% (t = 6.612, P = 0.003) respectively, indicating the
      down-regulation of PP2Ac up-regulated the activity of JNK/c-Jun/AP-1 pathway.
      Blocking the JNK pathway using a selective inhibitor, SP600125, induced G2/M cell
      cycle arrest and repressed cell proliferation. Cell viability decreased (31.38 +/
      1.33)% (t = 40.930, P < 0.001) after treatment with JNK inhibitor for 72 hours.
      CONCLUSION: Suppressed expression of PP2Ac in pancreatic cancer facilitated cell
      growth through up-regulating the activity of JNK/c-Jun/AP-1 pathway.

PMID- 24721346
TI  - [Expression and significance of leukemia inhibitory factor in human pancreatic
      cancer].
AB  - OBJECTIVE: To explore the expression of leukemia inhibitory factor (LIF) and its
      clinicopathological significance in human pancreatic ductal adenocarcinoma (PDAC)
      and examine its regulatory role of biological behaviors of pancreatic cancer
      cells. METHODS: The expression of LIF protein in 53 paired paraffin-embedded PDAC
      specimens and adjacent non-cancerous pancreatic tissues were detected by
      immunohistochemistry. The relationship between their expressions and
      clinicopathological characteristics was analyzed.Western bolt was used to examine
      the expression of LIF level in 14 paired fresh PDAC specimens and adjacent non
      cancerous pancreatic tissues.Furthermore, Western blot and polymerase chain
      reaction (PCR) were used to detect the LIF-R mRNA and protein level of LIF in 6
      pancreatic cancer cell lines (AsPC-1, BxPC-3, PANC-1, SW-1990, Capan-2 and
      Miapaca-2). And the assays of MTT, invasion and migration were used to detect the
      effects of LIF in regulating cell proliferation, invasion and migration in
      pancreatic cancer cell lines. RESULTS: The expression of LIF increased in 53
      cases of PDAC versus paired normal tissues (66.0% vs 35.8%; t = 3.031, P =
      0.004). And its positive association with tumor TNM stage (chi2 = 3.635, P =
      0.057) and invasion depth (chi2 = 3.726, P = 0.054) had no statistical
      significance.Univariate analysis revealed that LIF may be a correlative adverse
      prognostic indicator for patients with PDAC (chi2 = 3.233, P = 0.072). The
      expression of LIF was much higher in 14 cases of PDAC than that in adjacent
      normal pancreatic tissues (t = 5.283, P < 0.01). The protein level of LIF was
      lower in Capan-2 cells than that in other 5 pancreatic cancer cell lines while
      mRNA level of LIF receptor was higher than that in other 5 cell lines. Also LIF
      could promote the proliferation, migration and invasion of Capan-2 cell (P <
      0.05). CONCLUSION: An over-expression of LIF may contribute to the development
      and progression of PDAC.LIF can promote the proliferation, migration and invasion
      in some pancreatic cancer cells.

PMID- 24721347
TI  - [Diagnosis and treatment of solid-pseudopapillary carcinoma of the pancreas].
AB  - OBJECTIVE: To summarize the institutional experiences of diagnosis, treatment and
      prognosis for solid-pseudopapillary carcinoma of the pancreas (SPCP). METHODS:
      Retrospective analyses were performed for 11 cases of SPCP diagnosed in recent 15
      years at Department of Abdominal Surgery, Cancer Institute and Hospital, Chinese
      Academy of Medical Sciences. RESULTS: There were 10 females and 1 male with an
      average age of 33 years. The locations included head (n = 7) and body and tail (n
      = 4).Five of them had pain in abdomen or back while another 6 were found
      accidentally. Their images were of solid-cystic tumors and all serum markers
      stayed within a normal range. All received en bloc resection. The average maximum
      diameter was 6 cm and the percentage of patients with lymph node metastases was
      36.4% (4/11). Their average follow-up period was 80.5 months. Two patients died
      postoperatively from hepatic metastases. And another 9 survived without relapse
      or metastasis. CONCLUSION: As one of rare pancreatic neoplasms with non-specific
      clinical characteristics, SPCP primarily affects young females. A definite
      diagnosis depends on pathological confirmation.Surgery is the first-choice
      treatment with a favorable prognosis.Radical resection with R0 margin is crucial
      to long-term postoperative survival.

PMID- 24721348
TI  - [Distribution and pathogenicity of Ureaplasma urealyticum serotypes in female
      cervix].
AB  - OBJECTIVE: To explore the distribution of Ureaplasma urealyticum (UU) serotypes
      in cervix secretion and examine the relationship between serotype and host age,
      clinical phenotypes and vaginal Lactobacilli. METHODS: A total of 444 cervical
      secretion samples were collected from healthy subjects and 342 cervical secretion
      samples from females with genital diseases between October and December 2012 at
      Sir Run Run Shaw Hospital, Zhejiang University School of Medicine. Biovar-typing
      was performed by PCR based on multiple-banded antigen (MBA) gene. And serotyping
      was performed by real-time PCR based on specific nucleotide sequences. RESULTS:
      The positive rate of UU in disease group (62.6%, 214/342) was significantly
      higher than that in healthy group (44.1%, 196/444, P < 0.05). The main serotypes
      in both groups were 1, 3, 6, 9 and mixed infection.No significant difference
      existed between host age and UU serotype (P > 0.05) . The distribution of
      serotype 3 in disease and Lactobacilli abnormal group was significantly higher
      than that in healthy and Lactobacilli normal groups (13.1% (28/214) vs 5.1%
      (10/196) , 12.2% (27/221) vs 5.8% (11/189) , both P < 0.05) whereas the
      distribution of serotype 6 in disease and Lactobacilli abnormal groups was
      significantly lower than that in healthy and Lactobacilli normal groups (14.0%
      (30/214) vs 30.1% (59/196) , 16.3% (36/221) vs 28.0% (53/189) , both P < 0.05).
      CONCLUSIONS: 1, 3, 6, 9 and mixed infection are the main UU serotypes in female
      cervix.Serotype 3 and mixed infection may be associated with female genital
      infection.

PMID- 24721349
TI  - [Blood glucose control and its influencing factors in elderly type 2 diabetics
      under different health care levels].
AB  - OBJECTIVE: To compare the status of blood glucose control in elderly type 2
      diabetics under different health care levels and analyze its influencing factors.
      METHODS: Using cross-sectional and field survey methods, 688 elderly type 2
      diabetics aged over 60 years undergoing long-term annual physical examination at
      PLA General Hospital in May 2009(veteran group) were recruited. And 409 patients
      aged over 60 years with type 2 diabetes were selected from a community health
      survey in Beijing from September 2009 to June 2010(community group). According to
      the diabetic control standards of Chinese Type 2 Diabetes Prevention Guide(2010),
      a comparison of blood glucose control status between two groups were conducted.
      RESULTS: The mean HbA1c level was 6.6% +/- 1.0% in the veteran group. And there
      were 50.6% patients with HbA1c <6.5% and 76.3% with HbA1c <7%. In the community
      group, the mean HbA1c level was 7.1% +/- 1.4% and the success rates of HbA1c were
      40.6% and 55.7% respectively. The status of blood glucose control in the veteran
      group was significantly superior to that in the community group (P < 0.05). The
      comprehensive rates of achieving control target goals for blood glucose, blood
      pressure and blood lipids were higher in the veteran group than that in the
      community group (11.5% vs 2.0%, P < 0.001). The success rates of HbA1c for
      diabetics diagnosed after age 60 years were better than those diagnosed before
      age 60 years (P < 0.05). Logistic regression analysis showed that different
      health care levels, gender, duration of diabetes, age of onset and total
      cholesterol were crucial factors for achieving target goal of HbA1c in both
      groups (P < 0.05). CONCLUSION: The status of blood glucose control was much
      better in the veteran group than that in the community group. And the blood
      glucose control level in the patients diagnosed as diabetes after age 60 years
      was superior to that in those diagnosed before age 60 years.

PMID- 24721350
TI  - [Distribution of IgG subclasses of TgAb and TPOAb in sera from patients with
      Graves' disease, Graves' disease plus Hashimoto's thyroiditis and Hashimoto's
      thyrotoxicosis].
AB  - OBJECTIVE: To evaluate the distribution of IgG subclasses of TgAb and TPOAb in
      sera from patients with Graves' disease (GD), Graves' disease plus Hashimoto's
      thyroiditis (GH) and Hashimoto's thyrotoxicosis. METHODS: Patients with GD (n =
      33), GH (n = 31) or Hashimoto's thyrotoxicosis (n = 18) diagnosed by fine needle
      aspiration cytology at Department of Endocrinology of Peking University First
      Hospital, Beijing Haidian Hospital, China-Japan Friendship Hospital and Civil
      Aviation General Hospital during the period from January 2010 to May 2013 were
      enrolled. All of them had TgAb and TPOAb. The total serum IgG and IgG subclasses
      of TgAb and TPOAb were detected by antigen-specific enzyme-linked immunosorbent
      assay (ELISA). The prevalence and relative amount of IgG subclasses were
      calculated and compared among three groups. RESULTS: The levels of TRAb in GD
      group (21.80(7.53, 40) U/L) were significantly higher than those in GH
      (7.30(3.10, 25.40) U/L) (P = 0.000) and Hashimoto's thyrotoxicosis groups
      (4.90(1.69, 16.43) U/L) (P = 0.003). And no significant differences were found in
      the levels of TgAb and TPOAb. The prevalence of TgAb IgG3 subclass in Hashimoto's
      thyrotoxicosis group (66.7%) was higher than GD group (35.5%) and GH group
      (36.4%) and the difference was close to significance (P = 0.066). There were
      significant differences of relative amount of TgAb IgG2 and TgAb IgG4 among three
      groups (P = 0.039 and 0.013), and GD patients had higher relative amounts of TgAb
      IgG2 (0.59(0.34, 0.94)) and TgAb IgG4 (0.57(0.28, 0.97)) than GH patients (TgAb
      IgG2, 0.31(0.23, 0.34); TgAb IgG4, 0.26(0.09, 0.48)) or patients with Hashimoto's
      thyrotoxicosis (TgAb IgG2, 0.32(0.24, 0.83); TgAb IgG4, 0.33(0.10, 0.65)) (for
      TgAb IgG2, P = 0.009 and 0.167; for TgAb IgG4, P = 0.005 and 0.041 respectively).
      No significant difference was found in the prevalence of each TPOAb IgG subclass.
      The difference of relative amount of TPOAb IgG2 among three groups was close to
      significance (P = 0.069). And the relative amount was higher in sera from GD
      patients (0.39 +/- 0.04) than that in GH patients (0.29 +/- 0.13) or patients
      with Hashimoto's thyrotoxicosis (0.26 +/- 0.02) (P = 0.104 and 0.002
      respectively). CONCLUSION: The patients with high levels of TgAb IgG2, TgAb IgG4
      and TPOAb IgG2 subclasses have a greater risk of GD. The IgG subclass
      distribution of TgAb and TPOAb might help to differentiate the causes of
      thyrotoxicosis in autoimmune thyroid diseases.

PMID- 24721351
TI  - [Meta-analysis of prognostic tests in neonates over 35-week gestational age with
      hypoxic-ischemic encephalopathy].
AB  - OBJECTIVE: To explore the prognostic value of currently used clinical tests in
      neonatal patients over 35-week gestational age with perinatal asphyxia and
      hypoxic-ischemic encephalopathy (HIE). METHODS: "Neonate""hypoxic-ischemic
      encephalopathy " and "prognostic test" were used as key words. Searches were made
      on the databases of PubMed, EMBASE, CNKI and WanFang for studies published
      between January 1980 and December 2012. Studies were included if they (1)
      evaluated outcome in over 35-week gestational age neonates with perinatal
      asphyxia or HIE; (2) reported outcomes at minimal follow-up age of 18 months; (3)
      confirmed neurodevelopment with favorable or adverse outcomes. RevMan 5.2
      software 1.4 was used for meta-analysis. And the evaluation criteria of each
      study were employed to assess and analyze the results comprehensively. RESULTS:
      Among 260 relevant studies, 20 were included. There are 7 tests contented our
      inclusion criteria: amplitude-integrated electroencephalography (aEEG), magnetic
      resonance imaging (MRI:T1/T2 weighted imaging, diffusion weighted imaging (DWI),
      apparent diffusion coefficient (ADC), magnetic resonance spectroscopy (MR S)),
      cerebral ultrasound (CUS) and HIE stage. The most promising tests were aEEG:
      sensitivity 0.936 (95%CI: 0.897-0.964) ; specificity 0.884 (95%CI: 0.836- 0.921).
      In imaging, T1/T2-weighted MRI sensitivity 0.913 (95%CI: 0.850-0.956),
      specificity 0.630 (95%CI: 0.544-0.711); diffusion weighted MRI sensitivity 0.933
      (95%CI:0.817-0.956), specificity 0.694 (95%CI: 0.546-0.817); ADC sensitivity
      0.778 (95%CI: 0.664-0.867) , specificity 0.971 (95%CI: 0.898-0.996); MRS
      sensitivity 0.918 (95%CI: 0.804-0.977), specificity 0.642 (95%CI: 0.515-0.755).
      CUS sensitivity 0.683 (95%CI: 0.519-0.819), specificity 0.459 (95%CI: 0.295
      0.631). HIE stage sensitivity 0.967 (95%CI: 0.924-0.989) , specificity 0.314
      (95%CI: 0.241-0.394). CONCLUSIONS: These evidence suggests an important role for
      aEEG, MRI (T1/T2-weight, DWI, ADC), CUS and HIE stage. The sensitivity and
      specificity of aEEG are both relatively high; HIE stage has good sensitivity; in
      imaging, T1/T2-weight,DWI and MRS yield better sensitivity while ADC has the best
      specificity. Mild hypothermia treatment reduces the predictive value of
      evaluation system.Each test has its advantages and disadvantages. Thus an
      integrated use of a variety of prognostic tests centering on clinical
      neurological assessment is optimal.

PMID- 24721352
TI  - [Effects of penehyclidine inhalation on postoperative pulmonary complications of
      elderly patients after long-duration surgery].
AB  - OBJECTIVE: To explore the effects of penehyclidine inhalation on the incidence of
      pulmonary complications in elderly patients after long-duration surgery. METHODS:
      For this prospective, double-blind and randomized controlled trial, 90 elderly
      patients undergoing long-duration surgery ( >= 3 hours) under general anesthesia
      and transferred into intensive care unit (ICU) of Peking University First
      Hospital during February 14, 2012 to September 13, 2012 were enrolled. After
      extubation, they were randomized into 3 groups to receive an inhalation of
      penehyclidine hydrochloride, ipratropium bromide or normal saline for 3
      consecutive days. The primary endpoint was the incidence of pulmonary
      complications within 6 days post-extubation. RESULTS: The incidence of
      bronchospasm was 3.3%, 3.2% and 20.7% respectively. And the rate of aminophylline
      use was 0,0 and 10.3% respectively (P = 0.025 and P = 0.038); the airway tract
      spasm-free duration within 6 days after extubation was 5.8 (5.5-6.2), 5.8 (5.5
      6.2) and 5.3 (4.8-5.9) days (P = 0.028); the overall incidence of pulmonary
      complications was 70.0%, 71.0% and 75.9% (P = 0.865). CONCLUSIONS: For elderly
      patients after long-duration surgery, a prophylactic atomizing inhalation of
      penehyclidine decreases the incidence of bronchospasm and the rate of
      aminophylline use after extubation.However, the overall incidence of pulmonary
      complications has no change.

PMID- 24721353
TI  - [Correlated analysis of 5 fluorouracil metabolic enzymes with tumor response
      after SOX regimen neoadjuvant chemotherapy in advanced gastric cancer].
AB  - OBJECTIVE: To analyze the impact of mRNA expression of oral fluoropyrimidine (S
      1) metabolism on treatment outcomes in locally advanced gastric cancer patients
      on preoperative S-1 oxaliplatin-based chemotherapy. METHODS: Between June 2012
      and March 2013, 32 patients with preoperative AJCC stage II-III gastric cancer
      patients were enrolled. They received S-1 (80 mg.m-2 * d-1, days 1-14) and
      oxaliplatin (130 mg/m2, day 1) every 3 weeks and subsequently underwent
      gastrectomy with D2 lymphadenectomy. Paired tumor and normal fresh frozen tissues
      were collected to evaluate the mRNA levels of thymidylate synthase (TS),
      thymidine phosphorylase (TP), dihydropyrimidine dehydrogenase (DPD) and OPRT with
      quantitative reverse transcription(RT) -PCR. RESULTS: Among them, 21 (65.6%)
      patients had clinical tumor response and histological response occurred in 10
      (31.3%) patients. Quantitative RT-PCR results showed that OPRT mRNA expression
      was significantly higher in clinical tumor responders than non-responders (3.95
      +/- 0.81 vs 1.79 +/- 0.64, P = 0.005). Diffuse-type gastric cancer patients (n =
      22) demonstrated higher OPRT expression levels than intestinal-type(n = 10) ones
      (2.54 +/- 0.75 vs 1.49 +/- 0.56, P = 0.014). The mRNA expressions of TS and TP in
      gastric cancer tissues with lymph node (LN) metastasis (n = 13) were
      significantly higher than those in gastric cancer tissues without LN metastasis
      (n = 19, both P < 0.05) .Similar results were not found for comparing
      dihydropyrimidine dehydrogenase expression levels (all P > 0.05). CONCLUSION:
      OPRT, TS and TP may become potential predictive biomarkers in advanced gastric
      cancer patients on oral fluoropyrimidine (S-1)-based chemotherapy.

PMID- 24721354
TI  - [Clinical efficacies of laparoscopic-assisted rectal resection and transvaginal
      removal for middle or low rectal endometriosis].
AB  - OBJECTIVE: To explore the efficacies and safety of laparoscopic-assisted rectal
      resection and transvaginal removal for middle or low rectal endometriosis.
      METHODS: A total of 48 patients with middle or low rectal endometriosis
      undergoing laparoscopic-assisted transvaginal resection from May 2010 to December
      2012 at First Affiliated Hospital, Sun Yat-sen University were enrolled.
      Postoperative short and long-term complications and clinical efficacies were
      retrospectively analyzed. RESULTS: All cases underwent laparoscopic-assisted
      transvaginal rectal resection successfully.Neither conversion into laparotomy nor
      preventive colostomy was needed. Their average age was 34.4 (22-43) years. The
      locations were above peritoneal reflection (n = 19) and below (n = 29). The
      incidence of anastomotic leakage was 2.1% (n = 1). The mean operative duration
      was 78 (62-180) min and the length of hospital stay 7.5 days. Compared with
      preoperative period, their postoperative digestive and gynecological symptoms
      improved significantly (intestinal bleeding 0 vs 18 (37.5%), dysmenorrhea 1
      (2.1%) vs 48(100.0%) all P < 0.05). However, there was no change of constipation
      symptoms (6(12.5%) vs 5(10.4%), P > 0.05). CONCLUSION: Laparoscopic-assisted
      transvaginal resection for middle or low rectal endometriosis was efficacious,
      safe and worth popularizing.

PMID- 24721355
TI  - [Complicated effects of Gfi-1 on proliferation and apoptosis of murine 32D
      cells].
AB  - OBJECTIVE: To explore the relationship between growth factor independence 1 (Gfi
      1) and apoptosis as well as proliferation in 32D cell and observe the effects of
      Gfi-1 and N382S on 32D cell so as to further explore its possible mechanism of
      apoptosis and proliferation in hemopoietic stem cells. METHODS: 32D cells
      expressed a high level of Gfi-1 or its mutant N382S by plasmid transduction, cell
      apoptosis was examined by flow cytometry and the levels of Bax, signal transducer
      and activator of transcription 3 (STAT3) and Gfi-1 protein by Western blot.
      RESULTS: The apoptotic cell ratios were lower in the 32D/Gfi-1 groups than those
      in the 32D/puro groups (4.0% +/- 1.8%, 7.0% +/- 1.6%, 10.0% +/- 2.4% vs 6.0% +/-
      1.0%, 11.0% +/- 1.5% and 23.0% +/- 1.5% respectively, all P < 0.05)after culture
      for 48, 96 and 144 h. The apoptotic rates were compared between the 32D/N382S and
      32D/puro groups.However, there were no marked statistical difference (5.0% +/-
      1.3%, 12.0% +/- 2.1%, 21.0% +/- 2.2% vs 6.0% +/- 1.0%, 11.0% +/- 1.5%, 23.0% +/-
      1.5% respectively, P > 0.05).Interestingly, the number of 32D cells expressed Gfi
      1 decreased compared to the controls (0.96 * 106, 2.03 * 106, 3.47 * 106 vs 1.42
      * 106, 3.26 * 106, 6.12 * 106 respectively, all P < 0.05). But no marked
      difference existed between 32D/N382S groups and the controls (1.51 * 106, 3.36 *
      106, 6.54 * 106 vs 1.42 * 106, 3.26 * 106 and 6.12 * 106 respectively, P > 0.05)
      after culturing for 48, 96 and 144 h. The expression level of Bax decreased
      significantly in 32D/Gfi-1 groups (1.090 +/- 0.062 vs 1.707 +/- 0.025, P < 0.05),
      but showed no marked in 32D/N382S groups (1.710 +/- 0.062 vs 1.707 +/- 0.025, P >
      0.05), compared to 32D/puro groups. The expression level of STAT3 increased
      significantly in 32D/Gfi-1 groups (1.723 +/- 0.168 vs 1.203 +/- 0.168, P < 0.05)
      and 32D/N382S groups (1.797 +/- 0.292 vs 1.203 +/- 0.168, P < 0.05) compared to
      32D/puro groups. CONCLUSIONS: Gfi-1 inhibits cell apoptosis and
      proliferation.Such an effect is associated with Bax down-regulation.Zinc finger
      structure of Gfi-1 has no marked interaction with the expression of STAT3. And
      Gfi-1 is both unique and complicated in hemopoietic stem cells.

PMID- 24721356
TI  - [Effects of early digoxin treatment on hypoxia-induced pulmonary artery
      hypertension].
AB  - OBJECTIVE: To explore the effects of digoxin on hypoxia-induced pulmonary artery
      hypertension (PAH) and the possible mechanisms. METHODS: A total of 48 Sprague
      Dawley rats were randomly divided into 4 groups: normoxia control,
      normoxia+digoxin, hypoxia control and hypoxia+digoxin. The animals were exposed
      to chronic intermittent hypoxia (PO2: (10.5 +/- 0.5) %, 8:00-16:00) or room air
      for 21 days.Each rat received a daily intraperitoneal injection of either digoxin
      (1.0 mg * kg-1 * d-1) or an equal volume of vehicle, starting at the first day of
      hypoxia or normoxia. At Day 21, mean pulmonary arterial pressure (mPAP), right
      ventricular hypertrophy (RV/(LV+S)) and index of wall thickness of small
      pulmonary artery (WT% and WA%) among groups were compared. And in vitro the
      changes of pulmonary artery smooth muscle cells (PASMCs) proliferation were
      determined by methyl thiazolyl tetrazolium (MTT) assay. Migration assay was
      performed with a Transwell chamber.Real-time quantitative polymerase chain
      reaction (PCR) was performed to quantify the mRNA levels of smooth muscle cell
      phenotype markers such as smooth muscle-alpha-actin, calponin and smooth muscle
      22alpha under normoxic or hypoxic conditions in the absence or presence of
      digoxin. And the protein expressions of matrix metalloproteinase (MMPs) were
      determined by Western blot. RESULTS: Digoxin treatment significantly lowered
      mPAP, reduced WT% and WA% and right ventricular hypertrophy compared with those
      of the hypoxic group (mPAP: (27.3 +/- 2.7) vs (38.5 +/- 2.3) mmHg (1 mmHg = 0.133
      kPa); RV/(LV+S): (30.9 +/- 3.3)% vs (42.8 +/- 2.6)%, WT%: (21.7 +/- 3.6)% vs
      (39.3 +/- 2.0)%; WA%: (56.3 +/- 4.7)% vs (79.5 +/- 5.7)%, all P < 0.05). And in
      vitro, digoxin restored the hypoxia-induced inhibition of the expression of
      smooth muscle cell phenotype markers and prevented the hypoxia-induced activation
      of MMPs in PASMCs. CONCLUSION: Early digoxin therapy reduces pulmonary artery
      remodeling in hypoxia-induced PAH rat model and this effect is probably
      correlated with the inhibitions of proliferation, migration, phenotype switching
      and expression of MMPs induced by hypoxia in PASMCs.

PMID- 24721357
TI  - [Effects of S100A7 on the proliferation and invasiveness of esophageal squamous
      cell carcinoma EC9706 cells and possible mechanisms].
AB  - OBJECTIVE: To explore the expression of S100A7 in esophageal squamous cell
      carcinoma (ESCC) and examine the effect of S100A7 down-regulated expression
      mediated via RNA interfering on cell proliferation and invasion. METHODS: The
      expressions of S100A7 mRNA and protein were analyzed by in situ hybridization and
      immunohistochemistry.S100A7 siRNA was transfected into ESCC cell line EC9706 and
      the expressions of S100A7 mRNA and protein were detected by real-time polymerase
      chain reaction (PCR) and Western blot.Furthermore, the effects of down-regulated
      of S100A7 on cell proliferation and invasion were examine by Cell Counting Kit-8
      (CCK-8) and Boyden chamber respectively.Finally the effect of down-regulated
      expression of S100A7 on matrix metalloproteinase-2 (MMP-2) protein was analyzed
      by Western blot. RESULTS: Positive expression ratios of S100A7 mRNA and protein
      expressions in ESCC tissues (72.0% and 69.3%) were significantly higher than
      those in normal esophageal tissues (10.7% and 8.0%) (chi2 = 58.174 and 59.483,
      both P = 0.000). The expressions of S100A7 mRNA and protein in S100A7 siRNA group
      were markedly lower than those in untreated group (mRNA: 0.235 +/- 0.056 vs 1,
      protein: 0.119 +/- 0.025 vs 0.518 +/- 0.129, both P < 0.05). Additionally, the
      down-regulated expression of S100A7 resulted in the proliferation inhibition and
      the decreased invasiveness in EC9706 cells. And it was coupled with a down
      regulation of MMP-2 protein. CONCLUSION: S100A7 may play an essential role in the
      occurrence and development of ESCC and the decreased invasiveness of EC9706 cells
      mediated by the down-regulated expression of S100A7 may be closely associated
      with the down-regulation of MMP-2 protein.

PMID- 24721358
TI  - Epidemiology of fragility fractures.
AB  - As the world population of older adults-in particular those over age 85
      increases, the incidence of fragility fractures will also increase. It is
      predicted that the worldwide incidence of hip fractures will grow to 6.3 million
      yearly by 2050. Fractures result in significant financial and personal costs.
      Older adults who sustain fractures are at risk for functional decline and
      mortality, both as a function of fractures and their complications and of the
      frailty of the patients who sustain fractures. Identifying individuals at high
      risk provides an opportunity for both primary and secondary prevention. 

PMID- 24721359
TI  - Principles of comanagement and the geriatric fracture center.
AB  - This article describes the principles of comanagement in an optimized geriatric
      fracture center. This is a collaborative model of care that uses patient
      centered, protocol-driven care to standardize the care for most patient fragility
      fractures. This model also uses shared decision making and frequent communication
      to improve clinically relevant outcomes. The orthopedic and medical teams are
      equally responsible from admission to discharge and are responsible for daily
      evaluation and clinical management of the patient.

PMID- 24721360
TI  - Lean business model and implementation of a geriatric fracture center.
AB  - Geriatric hip fracture is a common event associated with high costs of care and
      often with suboptimal outcomes for the patients. Ideally, a new care model to
      manage geriatric hip fractures would address both quality and safety of patient
      care as well as the need for reduced costs of care. The geriatric fracture center
      model of care is one such model reported to improve both outcomes and quality of
      care. It is a lean business model applied to medicine. This article describes
      basic lean business concepts applied to geriatric fracture care and information
      needed to successfully implement a geriatric fracture center. It is written to
      assist physicians and surgeons in their efforts to implement an improved care
      model for their patients.

PMID- 24721361
TI  - Preoperative optimization and risk assessment.
AB  - Because most older adults with hip fractures require urgent surgical
      intervention, the preoperative medical evaluation focuses on the exclusion of the
      small number of contraindications to surgery, and rapid optimization of patients
      for operative repair. Although many geriatric fracture patients have significant
      chronic medical comorbidities, most patients can be safely stabilized for surgery
      with medical and orthopedic comanagement by anticipating a small number of common
      physiologic responses and perioperative complications. In addition to estimating
      perioperative risk, the team should focus on intravascular volume restoration,
      pain control, and avoidance of perioperative hypotension.

PMID- 24721362
TI  - Preoperative management of anticoagulation and antiplatelet agents.
AB  - This article describes current literature and treatment plans for managing
      anticoagulation and antiplatelet agents in patients presenting with hip
      fractures. Indications for anticoagulation and antiplatelet agents are discussed,
      and management techniques for when patients present with hip fractures are
      reviewed.

PMID- 24721363
TI  - Classification and surgical approaches to hip fractures for nonsurgeons.
AB  - The location and type of hip fracture, and the patient's activity level, help to
      determine the method of surgical repair. Nondisplaced femoral neck fractures are
      treated with screw fixation. Displaced fractures are treated with arthroplasty.
      If the patient is very active, the treatment of choice should be total hip
      replacement, whereas if the patient is less active, the treatment of choice is
      hemiarthroplasty. Intertrochanteric fractures are classified as stable (treated
      with a sliding hip screw) or unstable (treated with an intramedullary hip screw).
      Subtrochanteric fractures are classified as typical or atypical. All
      subtrochanteric fractures are treated with intramedullary hip screws.

PMID- 24721364
TI  - Special anesthetic consideration for the patient with a fragility fracture.
AB  - In this article, an overview is presented of perioperative management of the
      patient with a fragility fracture, including preoperative risk stratification and
      optimization, anesthesia risks, anesthesia options, and postoperative pain
      management. Issues of preoperative evaluation that are of concern for the
      anesthesiologist because of their direct effect on intraoperative care are
      discussed. A team interdisciplinary approach and good communication between
      specialties involved in care of elderly surgical patients is important for
      optimal patient outcomes and to avoid perioperative complications. Cooperation
      between anesthesiology and medicine is indispensable in reaching a reasonable
      consensus regarding preoperative evaluation and should occur on a case-by-case
      basis.

PMID- 24721365
TI  - Management of postoperative complications: general approach.
AB  - The goal of postoperative management is to promote early mobility and avoid
      postoperative complications, recognizing the potentially devastating impact of
      complications on elderly patients with hip fracture. The recommended approach
      involves early mobilization; freedom from tethers (indwelling urinary catheters
      and other devices); effective pain control; treating malnutrition; preventing
      pressure ulcers; reducing risk for pulmonary, urinary, and wound infections; and
      managing cognition. This carefully structured and patient-centered management
      provides older, vulnerable patients their best chance of returning to their
      previous level of functioning as quickly and safety as possible.

PMID- 24721366
TI  - Management of common postoperative complications: delirium.
AB  - Delirium is a common postoperative surgical complication associated with poor
      outcomes. The complexity of delirium demands that each patient be assessed
      individually and a tailored prevention and treatment regimen be put in place.
      Nonpharmacologic and pharmacologic strategies are available to achieve this goal.

PMID- 24721367
TI  - Management of postoperative complications: anemia.
AB  - Anemia is extremely common following hip fracture. Consistent data from
      randomized trials show that transfusion of less blood, with a transfusion
      threshold around 8 g/dL hemoglobin concentration, is preferable to a traditional
      threshold of 10 g/dL. Adoption of a lower threshold leads to at least equivalent
      clinical outcomes, with much less exposure to transfusion costs and risks. The
      most common complication of transfusion is circulatory overload. Future research
      may elucidate the optimal transfusion threshold for these elderly patients and
      address the specific needs of subgroups of patients, including those with acute
      coronary syndrome or chronic kidney disease.

PMID- 24721368
TI  - Venous thromboembolism and postoperative management of anticoagulation.
AB  - Deep venous thrombosis and pulmonary embolism are common after fragility fracture
      surgery, although the incidence is decreasing over time. Prophylaxis is
      important, because it is effective; additionally, the consequences are
      significant. Several medications are available for prophylaxis, and the choice of
      agent should be determined based on patient and surgery characteristics, and
      balancing of venous thromboembolism (VTE) and bleeding risk. A comprehensive
      approach to VTE prophylaxis includes consideration of a pharmacologic agent and
      nonpharmacologic management.

PMID- 24721369
TI  - Management of postoperative complications: cardiovascular disease and volume
      management.
AB  - Postoperative cardiovascular complications are common, predictable, and typically
      treatable in geriatric patients who have sustained fractures. Although
      intervention-specific data are sparse, observational evidence from high
      performing geriatric fracture centers coupled with an understanding of geriatric
      principles can serve as a basis for treatment guidelines. Many patients can be
      safely and effectively managed with close attention to intravascular volume
      status, heart rate control, and minimization of other physiologic stresses,
      including pain and delirium. Many chronic cardiovascular therapies may be harmful
      in the immediate postoperative period, and can usually be safely omitted or
      attenuated until hemodynamic stability and mobility have been restored. 

PMID- 24721370
TI  - Transitions of care and rehabilitation after fragility fractures.
AB  - Transitions in care are a vulnerable time period for patients during which
      unintended errors may occur. This article discusses potential risks that could
      occur during care transitions, suggested improvements, and the transition from
      hospital to skilled nursing facilities for patients needing rehabilitation after
      their discharge from the hospital. Different rehabilitation settings and their
      reimbursement are reviewed. Common potential medical conditions arising in
      patients undergoing rehabilitation, rehabilitation goals, and secondary
      prevention also are discussed. 

PMID- 24721371
TI  - Secondary prevention after an osteoporosis-related fracture: an overview.
AB  - This article is an overview of the status of postfracture secondary prevention
      programs. The concept of fracture risk, the inclusion of fracture risk in
      clinical practice guidelines for osteoporosis, and how fracture risk has
      contributed to the development of postfracture secondary prevention programs are
      described. The scope of postfracture secondary prevention programs, the gaps in
      care that persist despite these initiatives, and the potential reasons for these
      gaps are also described. Recommendations for future research in the area of
      postfracture secondary prevention are provided.

PMID- 24721372
TI  - Postoperative prevention of falls in older adults with fragility fractures.
AB  - The postoperative period after correction of a fragility fracture is usually
      associated with functional deconditioning. This deconditioning is caused by
      multiple factors associated with a higher risk of falls during the immediate
      postoperative period and after discharge. Identification of risk and appropriate
      fall prevention interventions in these patients are pivotal. In this article, an
      overview is presented of the strategies to identify falls risk in postoperative
      patients after suffering a fragility fracture. Evidence is presented favoring
      targeted multicomponent intervention for falls prevention rather than a single
      intervention in fractured older patients at high risk of new falls and fractures.

PMID- 24721373
TI  - Atypical femur fractures.
AB  - Atypical femur fractures were first reported in 2007 and are now recognized as a
      unique clinical entity. They occur along the shaft of the femur extending from
      the subtrochanteric region proximally to the distal femoral metaphysis. These
      fractures have an increased incidence in patients taking bisphosphonates for
      osteoporosis and develop as stress reactions in the lateral cortex of the femoral
      shaft. The fractures often have a distinct radiographic appearance with
      thickening or beaking of the lateral cortex. Treatment should be initiated
      immediately. There is a higher incidence of complications with atypical
      fractures. Early detection of these fractures can greatly reduce morbidity. 

PMID- 24721374
TI  - Fragility fractures requiring special consideration: vertebral fractures.
AB  - The treatment of osteoporotic vertebral fractures is complicated because of the
      comorbid conditions of the elderly patient. Underlying osteoporosis leads to
      malalignment of the weakened bone and impedes fracture fixation. The treatment of
      osteoporotic vertebral fractures is widely empirical, because standardized and
      accepted treatment evidence-based concepts are missing for certain fracture
      types. As in other osteoporotic fractures in the elderly, the key for good
      outcome may be a combination of interdisciplinary treatment approaches and
      adapted surgical procedures. This article gives an overview of the underlying
      problems and possible treatment strategies for treatment of osteoporotic
      vertebral fractures in geriatric patients.

PMID- 24721375
TI  - Fragility fractures requiring special consideration: pelvic insufficiency
      fractures.
AB  - Fractures of the pelvis and acetabulum in osteoporotic bone represent an
      important subset of fragility fractures. Pelvic fractures in the elderly patient
      carry a significant 1-year mortality risk, comparable to that of hip fractures.
      Patients often lose their ability to function independently in the community. In
      this group, treatment of their bone density is essential to reducing their risk
      of further fractures. A thorough discussion of the likely course of recovery, the
      prolonged need for pain medications, and the risks and benefits of intervention
      can help patients and their families cope with the disability.

PMID- 24721376
TI  - Fragility fractures.

PMID- 24721377
TI  - Letter to the Editor regarding "Parental perception of speech and tongue mobility
      in three-year olds after neonatal frenotomy".

PMID- 24721378
TI  - The proteasomes of two marine decapod crustaceans, European lobster (Homarus
      gammarus) and Edible crab (Cancer pagurus), are differently impaired by heavy
      metals.
AB  - The intracellular ubiquitin-proteasome system is a key regulator of cellular
      processes involved in the controlled degradation of short-living or
      malfunctioning proteins. Certain diseases and cellular dysfunctions are known to
      arise from the disruption of proteasome pathways. Trace metals are recognized
      stressors of the proteasome system in vertebrates and plants, but their effects
      on the proteasome of invertebrates are not well understood. Since marine
      invertebrates, and particularly benthic crustaceans, can be exposed to high metal
      levels, we studied the effects of in vitro exposure to Hg(2+), Zn(2+), Cu(2+),
      and Cd(2+) on the activities of the proteasome from the claw muscles of lobsters
      (Homarus gammarus) and crabs (Cancer pagurus). The chymotrypsin like activity of
      the proteasome of these two species showed different sensitivity to metals. In
      lobsters the activity was significantly inhibited by all metals to a similar
      extent. In crabs the activities were severely suppressed only by Hg(2+) and
      Cu(2+) while Zn(2+) had only a moderate effect and Cd(2+) caused almost no
      inhibition of the crab proteasome. This indicates that the proteasomes of both
      species possess structural characteristics that determine different
      susceptibility to metals. Consequently, the proteasome-mediated protein
      degradation in crab C. pagurus may be less affected by metal pollution than that
      of the lobster H. gammarus. 

PMID- 24721379
TI  - Jacquet erosive diaper dermatitis: a not-so-rare syndrome.

PMID- 24721380
TI  - Solid-state NMR studies for the determination of 11B electric field-gradient
      tensor orientations in P/B Frustrated Lewis Pairs and related systems.
AB  - A solid state NMR method is described for measuring the angle Theta specifying
      the orientation of the principal component of the (11)B electric field gradient
      tensor relative to the (11)B(...31)P internuclear vector of (11)B-(31)P spin
      pairs. It is based on the anisotropic dephasing of (11)B spins in the dipolar
      field of (31)P nuclei via (11)B{(31)P} Rotational Echo DOuble Resonance (REDOR)
      experiments. The method is applied to four solid borane-phosphane compounds
      related to Frustrated Lewis Pair (FLP) chemistry. Results determined by numerical
      line shape simulations are found in excellent agreement with theoretically
      calculated values using advanced DFT methods. The angle Theta, which can be
      measured with an estimated precision of +/-5 degrees , offers a clear
      spectroscopic distinction between classical Lewis-acid/base adducts and active
      Frustrated Lewis pairs (FLPs).

PMID- 24721381
TI  - A fast and simple label-free immunoassay based on a smartphone.
AB  - Despite the continuous advancements in bio-molecular detection and fluidic
      systems integration, the realization of portable and high performance devices for
      diagnostic applications still presents major difficulties, mostly because of the
      need to combine adequate sensitivity with low cost of production and operational
      simplicity and speed. In this context, we propose a compact device composed of a
      smartphone and a custom-designed cradle, containing only a disposable sensing
      cartridge, a tiny magnetic stirrer and a few passive optical components. The
      detection principle is the previously proposed Reflective Phantom Interface that
      is based on measuring the intensity of light reflected by the surface of an
      amorphous fluoropolymer substrate, which has a refractive index very close to
      that of the aqueous sample solution and hosts various antibodies immobilized
      within spots. The reflectivity of dozens of spots is monitored in real time by
      the phone's camera using the embedded flash LED as the illumination source. We
      test the performance of the combined device targeting heterologous
      immunoglobulins and antigens commonly used as markers for diagnoses of hepatitis
      B and HIV. Target concentrations as low as a few ng/ml can be rapidly and
      robustly determined by comparing the rate of increase of the signal after the
      addition of the sample with that measured after the subsequent addition of a
      standard solution with known concentration. The features of the proposed system
      enable the realization of novel handheld biosensing devices suitable for those
      applications where multiple targets have to be rapidly detected even without the
      presence of trained personnel. 

PMID- 24721382
TI  - Aerosol sample inhomogeneity with debris from the Fukushima Daiichi accident.
AB  - Radionuclide aerosol sampling is a vital component in the detection of nuclear
      explosions, nuclear accidents, and other radiation releases. This was proven by
      the detection and tracking of emissions from the Fukushima Daiichi incident
      across the globe by IMS stations. Two separate aerosol samplers were operated in
      Richland, WA following the event and debris from the accident were measured at
      levels well above detection limits. While the atmospheric activity concentration
      of radionuclides generally compared well between the two stations, they did not
      agree within uncertainties. This paper includes a detailed study of the aerosol
      sample homogeneity of (134)Cs and (137)Cs, then relates it to the overall
      uncertainty of the original measurement. Our results show that sample
      inhomogeneity adds an additional 5-10% uncertainty to each aerosol measurement
      and that this uncertainty is in the same range as the discrepancies between the
      two aerosol sample measurements from Richland, WA. 

PMID- 24721383
TI  - Evolution of the stapeliads (Apocynaceae-Asclepiadoideae) - repeated major
      radiation across Africa in an Old World group.
AB  - The stapeliads of the Ceropegieae (Apocynaceae-Asclepiadoideae), are
      approximately 340 species of stem-succulents placed in around 30 genera, found in
      semi-arid parts of the Old World. Here we sampled 192 species (i.e. nearly two
      thirds of the total) from across the full geographic range of the group and
      analysed data from the two nuclear regions (nuclear ribosomal ITS and ncpGS) and
      five plastid regions (psbA-trnH intergenic spacer, rps16 intron, trnL-trnF
      intergenic spacer, trnS-trnG intergenic region and the non-coding rpl32-trnL
      region). We find that the stapeliads radiated first in the northern hemisphere
      from Africa to southern Europe and Myanmar. This radiation subtends a grade of
      minor clades in the south-western corner of the African continent. These were
      followed by a single clade containing major radiation back across Africa from
      South Africa to tropical Arabia (but no further east than Dhofar, Oman), which
      includes also a single early spread into Madagascar. We establish the monophyly
      of many of the genera, such as Echidnopsis Hook.f., Hoodia Hook., Huernia R. Br.,
      Piaranthus R. Br., Rhytidocaulon P.R.O. Bally and Tridentea Haw., but find that
      Duvalia Haw., Orbea Haw., Stapelia L. and Tromotriche Haw. are polyphyletic. We
      show that in certain vegetative features, there is broad cohesion across clades.
      Florally, on the other hand, the stapeliads exhibit considerable plasticity and
      we are able to show that very differently shaped flowers as well as large and
      small flowers evolved repeatedly among closely related species.

PMID- 24721384
TI  - Translation and validation of European organization for research and treatment of
      cancer quality of life Questionnaire -C30 into Moroccan version for cancer
      patients in Morocco.
AB  - BACKGROUND: Understanding the effects of cancer on the quality of life of
      affected patients is critical to clinical research as well as to optimal
      management and care. The aim of this study was to adapt the European Organization
      for Research and Treatment of Cancer Quality of Life Questionnaire-C30 (EORTC QLQ
      C30) questionnaire into Moroccan Arabic and to determine its psychometric
      properties. After translation, back translation and pretesting of the pre-final
      version, the translated version was submitted to a committee of professionals
      composed by oncologists and epidemiologists. The psychometric properties were
      tested in patients with cancer. Internal consistency was tested using Cronbach's
      alpha and the test-retest reliability using interclass correlation coefficients.
      Construct validity was assessed by examining item-convergent and divergent
      validity. It was also tested using Spearman's correlation between QLQ-C30 scales
      and EQ-5D. RESULTS: The study was conducted in 125 patients. The Moroccan version
      was internally reliable, Cronbach's alpha was 0.87 for the total scale and ranged
      from 0.34 to 0.97 for the subscales. The intraclass correlation coefficient of
      the test-retest reliability ranged from 0.64 for "social functioning" to 0.89 for
      "physical activities" subscales. The instrument demonstrated a good construct and
      concomitant validity. CONCLUSIONS: We have developed a semantically equivalent
      translation with cultural adaptation of EORTC QLQ-C30 questionnaire. The
      assessment of its measurement properties showed that it is quite reliable and a
      valid measure of the effect of cancer on the quality of life in Moroccan
      patients.

PMID- 24721385
TI  - Using the community-based health planning and services program to promote skilled
      delivery in rural Ghana: socio-demographic factors that influence women
      utilization of skilled attendants at birth in northern Ghana.
AB  - BACKGROUND: The burden of maternal mortality in sub-Saharan Africa is enormous.
      In Ghana the maternal mortality ratio was 350 per 100,000 live births in 2010.
      Skilled birth attendance has been shown to reduce maternal deaths and
      disabilities, yet in 2010 only 68% of mothers in Ghana gave birth with skilled
      birth attendants. In 2005, the Ghana Health Service piloted an enhancement of its
      Community-Based Health Planning and Services (CHPS) program, training Community
      Health Officers (CHOs) as midwives, to address the gap in skilled attendance in
      rural Upper East Region (UER). The study determined the extent to which CHO
      midwives skilled delivery program achieved its desired outcomes in UER among
      birthing women. METHODS: We conducted a cross-sectional household survey with
      women who had ever given birth in the three years prior to the survey. We
      employed a two stage sampling techniques: In the first stage we proportionally
      selected enumeration areas, and the second stage involved random selection of
      households. In each household, where there is more than one woman with a child
      within the age limit, we interviewed the woman with the youngest child. We
      collected data on awareness of the program, use of the services and factors that
      are associated with skilled attendants at birth. RESULTS: A total of 407
      households/women were interviewed. Eighty three percent of respondents knew that
      CHO-midwives provided delivery services in CHPS zones. Seventy nine percent of
      the deliveries were with skilled attendants; and over half of these skilled
      births (42% of total) were by CHO-midwives. Multivariate analyses showed that
      women of the Nankana ethnic group and those with uneducated husbands were less
      likely to access skilled attendants at birth in rural settings. CONCLUSIONS: The
      implementation of the CHO-midwife program in UER appeared to have contributed to
      expanded skilled delivery care access and utilization for rural women. However,
      women of the Nankana ethnic group and uneducated men must be targeted with health
      education to improve women utilizing skilled delivery services in rural
      communities of the region.

PMID- 24721386
TI  - Reply to Chatburn and colleagues letter.

PMID- 24721387
TI  - Controlling mechanical ventilation in acute respiratory distress syndrome with
      fuzzy logic.
AB  - PURPOSE: The current ventilatory care goal for acute respiratory distress
      syndrome (ARDS) and the only evidence-based approach for managing ARDS is to
      ventilate with a tidal volume (VT) of 6 mL/kg predicted body weight (PBW).
      However, it is not uncommon for some caregivers to feel inclined to deviate from
      this strategy for one reason or another. To accommodate this inclination in a
      rationalized manner, we previously developed an algorithm that allows for VT to
      depart from 6 mL/kg PBW based on physiological criteria. The goal of the present
      study was to test the feasibility of this algorithm in a small retrospective
      study. MATERIALS AND METHODS: Current values of peak airway pressure, positive
      end-expiratory pressure (PEEP), and arterial oxygen saturation are used in a
      fuzzy logic algorithm to decide how much VT should differ from 6 mL/kg PBW and
      how much PEEP should change from its current setting. We retrospectively tested
      the predictions of the algorithm against 26 cases of decision making in 17
      patients with ARDS. RESULTS: Differences between algorithm and physician VT
      decisions were within 2.5 mL/kg PBW, except in 1 of 26 cases, and differences
      between PEEP decisions were within 2.5 cm H2O, except in 3 of 26 cases. The
      algorithm was consistently more conservative than physicians in changing VT but
      was slightly less conservative when changing PEEP. CONCLUSIONS: Within the limits
      imposed by a small retrospective study, we conclude that our fuzzy logic
      algorithm makes sensible decisions while at the same time keeping practice close
      to the current ventilatory care goal.

PMID- 24721388
TI  - Family experience with intensive care unit care: association of self-reported
      family conferences and family satisfaction.
AB  - PURPOSE: A family conference is recommended as a best practice to improve
      communication in the intensive care unit (ICU), but this can be challenging given
      the setting. This study examined whether family members who reported that a
      family conference occurred had higher satisfaction than those who did not report
      that a conference was held. MATERIALS AND METHODS: The study used a retrospective
      data analysis of family satisfaction based on family member's responses to a
      questionnaire. Families of all the patients admitted to ICUs of 2 quaternary
      hospitals in an integrated health system were surveyed. RESULTS: The families of
      457 patients who matched the inclusion and exclusion criteria were surveyed with
      a 55.6% response rate. Family satisfaction with decision making was significantly
      higher (83.6 vs 78.2, P=.0211) for families who reported that family conferences
      occurred. No significant difference in the satisfaction with care and overall
      satisfaction scores was found (84.2 vs 80.0, P=.10). Patients whose families
      reported a family conference were older and had higher mortality. CONCLUSION:
      This study confirms that families who report attending family conferences are
      more satisfied with decision making in the ICU. This study highlights the need to
      increase communication in ICUs.

PMID- 24721389
TI  - Single dose acute toxicity testing for N,N-bis(2-mercaptoethyl)-N',N'
      diethylethylenediamine in beagles.
AB  - N,N-Bis(2-mercaptoethyl)-N',N'-diethylenediamine (BMEDA) is used in the
      preparation of the (188)Re-BMEDA-liposome as a chelator to deliver rhenium 188
      into liposomes. Although the safety of the (188)Re-BMEDA-liposome had been
      established, the use of BMEDA in preparing the liposome is of interest; however,
      an assessment of its safety is warranted. In this present work, we report on the
      acute toxicity study of BMEDA in beagles to identify doses causing no adverse
      effect and doses causing life-threatening toxicity. In a single dose 14-day
      systemic toxicity study conducted in beagles, BMEDA was without compound-related
      adverse effects at doses of up to 2mg/kg in a series of clinical observations and
      clinical pathology examinations. The results of these studies could aid in
      choosing doses for repeat-dose studies and in the selection of starting doses for
      Phase 1 human studies. 

PMID- 24721390
TI  - PSII manganese cluster: protonation of W2, O5, O4 and His337 in the S1 state
      explored by combined quantum chemical and electrostatic energy computations.
AB  - Photosystem II (PSII) is a membrane-bound protein complex that oxidizes water to
      produce energized protons, which are used to built up a proton gradient across
      the thylakoidal membrane in the leafs of plants. This light-driven reaction is
      catalyzed by withdrawing electrons from the Mn4CaO5-cluster (Mn-cluster) in four
      discrete oxidation steps [S1-(S4/S0)] characterized in the Kok-cycle. In order to
      understand in detail the proton release events and the subsequent translocation
      of such energized protons, the protonation pattern of the Mn-cluster need to be
      elucidated. The new high-resolution PSII crystal structure from Umena, Kawakami,
      Shen, and Kamiya is an excellent basis to make progress in solving this problem.
      Following our previous work on oxidation and protonation states of the Mn
      cluster, in this work, quantum chemical/electrostatic calculations were performed
      in order to estimate the pKa of different protons of relevant groups and atoms of
      the Mn-cluster such as W2, O4, O5 and His337. In broad agreement with previous
      experimental and theoretical work, our data suggest that W2 and His337 are likely
      to be in hydroxyl and neutral form, respectively, O5 and O4 to be unprotonated.
      This article is part of a Special Issue entitled: Photosynthesis Research for
      Sustainability: Keys to Produce Clean Energy.

PMID- 24721391
TI  - The site of regulation of light capture in Symbiodinium: does the peridinin
      chlorophyll a-protein detach to regulate light capture?
AB  - Dinoflagellates from the genus Symbiodinium form symbiotic associations with
      cnidarians including corals and anemones. The photosynthetic apparatuses of these
      dinoflagellates possess a unique photosynthetic antenna system incorporating the
      peridinin-chlorophyll a-protein (PCP). It has been proposed that the appearance
      of a PCP-specific 77K fluorescence emission band around 672-675 nm indicates that
      high light treatment results in PCP dissociation from intrinsic membrane antenna
      complexes, blocking excitation transfer to the intrinsic membrane-bound antenna
      complexes, chlorophyll a-chlorophyll c2-peridinin-protein-complex (acpPC) and
      associated photosystems (Reynolds et al., 2008 Proc Natl Acad Sci USA 105:13674
      13678).We have tested this model using time-resolved fluorescence decay kinetics
      in conjunction with global fitting to compare the time-evolution of the PCP
      spectral bands before and after high light exposure. Our results show that no
      long-lived PCP fluorescence emission components appear either before or after
      high light treatment, indicating that the efficiency of excitation transfer from
      PCP to membrane antenna systems remains efficient and rapid even after exposure
      to high light. The apparent increased relative emission at around 675nm was,
      instead, caused by strong preferential exciton quenching of the membrane antenna
      complexes associated with acpPC and reaction centers. This strong non
      photochemical quenching (NPQ) is consistent with the activation of xanthophyll
      associated quenching mechanisms and the generally-observed avoidance in nature of
      long-lived photoexcited states that can lead to oxidative damage. The acpPC
      component appears to be the most strongly quenched under high light exposure
      suggesting that it houses the photoprotective exciton quencher.

PMID- 24721392
TI  - Active glucagon-like peptide 1 quantitation in human plasma: a comparison of
      multiple ligand binding assay platforms.
AB  - There are a wide variety of ligand binding assay platforms available for
      implementation in present day bioanalytical laboratories. Selecting the platform
      that best suits a particular project's needs is highly dependent upon multiple
      assay characteristics. The active form of glucagon-like protein (GLP-1) is a
      biomarker of interest for type 2 diabetes (T2DM), and therefore a common target
      for quantitation. Previous projects requiring active GLP-1 measurements involved
      the use of a labor intensive ELISA, spurring an investigation towards other
      potential assay platforms. To that end, four separate ligand binding assay
      formats (standard ELISA, electrochemiluminescence, Gyrolab, and Singulex) were
      evaluated. The platforms were compared for numerous assay parameters including
      dynamic range, sample volume requirements, throughput, and cost. Additionally,
      thirty individual donor plasmas were run with each assay as representative study
      samples. Although our evaluation did not show any platform that was better than
      others in all assay characteristics, there was one that was best in sensitivity
      (Singulex) and one that was best in throughput and sample volume requirements
      (Gyrolab). The lack of a technology that was best in all categories underscores
      the importance of due diligence when selecting an assay platform; there are no
      silver bullets, and one must take into account what is necessary for project
      needs and the intended use of the data. 

PMID- 24721393
TI  - Development of a qPCR method to rapidly assess the function of NKT cells.
AB  - INTRODUCTION: NKT cells comprise a rare, but important subset of T cells which
      account for ~0.2% of the total circulating T cell population. NKT cells are known
      to have anti-tumor functions and rapidly produce high levels of cytokines
      following activation. Several clinical trials have sought to exploit the effector
      functions of NKT cells. While some studies have shown promise, NKT cells are
      approximately 50% lower in cancer patients compared to healthy donors of the same
      age and gender, thus limiting their therapeutic efficacy. These studies indicate
      that baseline levels of activation should be assessed before initiating an NKT
      cell based immunotherapeutic strategy. AIM: The goal of this study was to develop
      a sensitive method to rapidly assess NKT cell function. METHODS: We utilized
      artificial antigen presenting cells in combination with qPCR in order to
      determine NKT cell function in peripheral blood mononuclear cells from healthy
      donors and breast cancer patients. RESULTS: We found that NKT cell activation can
      be detected by qPCR, but not by ELISA, in healthy donors as well as in breast
      cancer patients following four hour stimulation. CONCLUSION: This method
      utilizing CD1d-expressing aAPCs will enhance our knowledge of NKT cell biology
      and could potentially be used as a novel tool in adoptive immunotherapeutic
      strategies.

PMID- 24721394
TI  - Combined PTEN Mutation and Protein Expression Associate with Overall and Disease
      Free Survival of Glioblastoma Patients.
AB  - Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) is a tumor
      suppressor commonly inactivated in glioblastoma multiforme (GBM), but the
      prognostic significance of PTEN remains controversial. Here, we demon- strate
      significant prognostic value of combined PTEN mutation and expression for the
      survival of patients with GBM on the basis of analysis of large-scale cancer
      genomic data. PTEN nonsense mutations associated with sig- nificantly shorter
      disease-free survival and overexpression of PTEN protein linked to shorter
      disease-free and overall survival of patients with GBM. PTEN nonsense mutations
      correlated with decreased p53 and Gata3 protein levels and increased genomic
      instability in human GBM tissues. Expression of nonsense PTEN mutant decreased
      p53 and Gata3 levels, producing increased DNA damage both in vitro and in vivo.
      Mice carrying xenograft tumors with nonsense PTEN mutant displayed significantly
      shorter survival. Our data demonstrated the prognostic value of combined PTEN
      mutation and protein expression for patients with GBM and highlighted distinct
      biologic effects of nonsense and missense mutations of PTEN. 

PMID- 24721395
TI  - Hyperkeratotic cutaneous vascular malformation associated with familial cerebral
      cavernous malformations (FCCM) with KRIT1/CCM1 mutation.

PMID- 24721396
TI  - [Effect of PLGA nanoparticles conjugated with anti-OX40/anti-AFP mAbs on
      cytotoxicity of CTL cells against hepatocellular carcinoma].
AB  - OBJECTIVE: To evaluate the effect of anti-OX40 and anti-AFP antibodies conjugated
      onto poly(DL-lactide-co-glycolide)-nanoparticles (PLGA-NPs) on the cytotoxic
      activity of AFP158-166; -specific cytotoxic T lymphocyte (CTL) against
      hepatocellular carcinoma cells in vitro. METHODS: PLGA-NPs were prepared by oil
      in-water single emulsion solvent evaporation method and covalently conjugated
      with anti-OX40 and anti-AFP monoclonal antibodies. Scanning electron microscopy
      (SEM) was utilized for the characterization of the surface morphology and
      estimation of the size of the PLGA-NPs. The mean diameter and zeta potential of
      the nanoparticles were measured by dynamic light scattering (DLS) performed in a
      Zetasiser Nano Series ZEN3600. Antibody conjugation efficiency was determined
      using bicinchoninic acid (BCA) protein assay. Dendritic cells (DCs) were induced
      from human peripheral blood mononuclear cells (PBMCs) in the presence of GM-CSF
      and IL-4, and loaded with AFP158-166; peptide to generate AFP-specific CTL
      (CTL/AFP158-166;). WST-1, ELISA and lactate dehydrogenase (LDH) methods were
      respectively used to examine the effects of the anti-OX40/anti-AFP-NPs on
      CTL/AFP158-166; proliferation, IL-2 and IFN-gamma production, and cytotoxicity
      against the tumor cells. RESULTS: The obtained nanoparticles were found to be of
      regular spherical shape and the smooth surface with an average diameter of (300+/
      42) nm and a negative zeta potential of -(25.12+/-5.34) mV. Approximately 100 MUg
      antibodies were conjugated to every milligram of the nanoparticles with a
      conjugation efficiency of about 25% as estimated by BCA protein assay.
      Proliferation and activation analysis revealed that anti-OX40/anti-AFP mAb-NPs
      significantly induced CTL proliferation and the secretion of IL-2 and IFN-gamma.
      The cytotoxicity assay showed that anti-OX40/anti-AFP-NPs markedly enhanced
      CTL/AFP158-166; specific killing on HepG2 cells but had no obvious effect on SMMC
      7721 cells. CONCLUSION: Anti-OX40 mAb and anti-AFP mAb conjugated to PLGA-NPs
      could stimulate CTL/AFP158-166; cell proliferation and cytokine production as
      well as enhancing their specific killing on AFP-positive hepatocellular carcinoma
      cells.

PMID- 24721397
TI  - [Overexpressed microRNA-93 inhibits the proliferation and promotes apoptosis of
      A172 glioma cells].
AB  - OBJECTIVE: To investigate the impact of microRNA-93 on the biological behaviors
      of A172 glioma cells by observing the changes of cell proliferation, cell cycle
      and apoptosis. METHODS: Real-time quantitative PCR (qRT-PCR) was applied to
      detect the expression of microRNA-93 in 2 samples of human normal brain tissues,
      10 samples of glioma tissues and 5 glioma cell lines. Artificially synthesized
      microRNA-93 mimic was transiently transfected into A172 glioma cells, and then
      the expression of microRNA-93 was tested by qRT-PCR. MTT assay was used to detect
      the cell proliferation of A172 glioma cells; apoptosis and cell cycle of A172
      glioma cells were measured by flow cytometry. RESULTS: MicroRNA-93 was over
      expressed in glioma tissues and glioma cell lines as compared with normal
      samples. The transient transfection of microRNA-93 mimic into A172 glioma cells
      significantly increased the expression of microRNA-93 in A172 glioma cells,
      promoted cell proliferation, raised the cell proportion in S phase, reduced the
      cell proportion in G1 phase, and inhibited cell apoptosis. CONCLUSION: MicroRNA
      93 was aberrantly over-expressed in glioma tissues and cell lines. Transient
      transfection of microRNA-93 mimic led to increased proliferation, G1-to-S cell
      cycle progression and reduced apoptosis in A172 glioma cells, indicating that
      micro-RNA-93 might be a new target for the diagnosis and treatment of glioma.

PMID- 24721398
TI  - [Effects of lipoic acid on cytokines and chemokines in astrocytes stimulated with
      lipopolysaccharide].
AB  - OBJECTIVE: To investigate the effects of lipoic acid (LA) on the release of TNF
      alpha, IL-1beta, IL-6, IL-10 and the expressions of chemokines in astrocytes
      stimulated with lipopolysaccharide (LPS). METHODS: Astrocytes were separated from
      the cerebral cortex of newly-born C57BL/6 mice (within 48 h after birth). After
      identification and purification, the second-generation astrocytes were stimulated
      with LPS (1 MUg/mL), and then treated with LA (100 MUg/mL). The production of
      nitric oxide (NO) was assayed by Griess assay. The levels of TNF-alpha, IL-1beta,
      IL-6 and IL-10 in supernatants were quantified by ELISA. The expressions of CC
      chemokine ligand-20 (CCL20), monocyte chemoattractive protein 1 (MCP-1) and
      macrophage inflammatory protein-1alpha (MIP-1alpha) mRNAs were detected using
      reverse transcription-PCR. RESULTS: Compared with PBS control, LPS significantly
      increased the production of TNF-alpha, IL-1beta and IL-6, but decreased the level
      of IL-10 in cultured astrocytes (P<0.05). LA treatment inhibited LPS-induced NO,
      TNF-alpha, IL-1beta and IL-6 production, and enhanced IL-10 secretion, and
      compared with LPS stimulation alone, the differences were statistically
      significant (P<0.05). In addition, LA treatment also suppressed the expressions
      of CCL20, MCP-1 and MIP-1alpha mRNA in astrocytes stimulated with LPS.
      CONCLUSION: LA inhibits neuroinflammatory response in LPS-activated astrocytes.
      The neuroprotection of LA is partly due to the inhibition of pro-inflammatory
      cytokines and chemokines derived from astrocytes.

PMID- 24721399
TI  - [The effect of LAMP2A shRNA on the resistance of breast cancer cells to
      paclitaxel].
AB  - OBJECTIVE: To prepare a recombinant lentiviral carring human lysosome-associated
      membrane protein type 2A (LAMP2A) gene shRNA, establish MDA-MB-231 cell line with
      a low expression of LAMP2A and observe the change in cell resistance to
      paclitaxel. METHODS: Four shRNAs were designed according to the sequencing
      analysis of LAMP2A mRNA. The pGLV-EGFP-shRNA lentiviral vector was established by
      gene recombination technology and was confirmed by DNA sequencing. The lentiviral
      vector and the packaging vector were used to cotransfect the HEK293T cells to
      obtain the lentivirus against LAMP2A mRNA, and the titer of the virus was
      determined. The constructed shRNA lentivirus was applied to infect human breast
      cancer cell line MDA-MB-231, and then the cells were screened with puromycin for
      two weeks. The inhibitive efficacy of the shRNA on the LAMP2A protein was
      determined by Western blotting. After the breast cancer cell line with a low
      expression of LAMP2A was treated with three different concentrations of
      paclitaxel (1, 10, 100 nmol/L), MTT assay was performed to observe the difference
      in the proliferation ability between the control group and the low LAMP2A
      expression groups. RESULTS: DNA sequencing revealed that the recombinant
      lentiviral plasmid was correctly constructed with the virus titer reaching
      2*10(8); TU/mL. The LAMP2A protein expression in the obtained breast cancer cell
      line dropped drastically. After the treatment with paclitaxel at 10 and 100
      nmol/L respectively, the drug resistance of cells with a low expression of LAMP2A
      was notably weaker than that of the control group (P<0.05). CONCLUSION: The
      recombinant shRNA lentiviral vector against human LAMP2A gene was successfully
      constructed, and the breast cancer cell line MDA-MB-231 transfected with it
      stably expressed a low level of LAMP2A. It was proved that the down-regulation of
      LAMP2A could reduce the resistance of breast cancer cells to paclitaxel.

PMID- 24721400
TI  - [Down-regulation of Zc3h12d expression in lung tissues of rats with acute lung
      injury induced by intestinal ischemia-reperfusion].
AB  - OBJECTIVE: To investigate the changes in the expression levels of CCCH zinc
      finger type-containing 12D(Zc3h12d) gene in lung tissues of rats with acute lung
      injury (ALI) induced by small intestinal ischemia-reperfusion (IIRI). METHODS:
      Forty healthy male Sprague-Dawley (SD) rats were equally randomized into sham
      operated group (control), 30-minute IIRI group, 60-minute IIRI group, 120-minute
      IIRI group. Rats in the IIRI groups were subjected to 60 minutes of superior
      mesenteric artery (SMA) occlusion and to reperfusion for 30, 60 and 120 minutes,
      respectively. Then the rats were sacrificed. Their lung tissues and sera were
      obtained, respectively. The lung tissues were examined for wet/dry (W/D) lung
      mass ratios and pathological changes through HE staining. The levels of TNF-alpha
      and IL-1beta in sera and lung tissue homogenates were detected by ELISA. The
      dynamic expression of Zc3h12d mRNA and protein in lung tissues was assayed by
      real-time quantitative PCR (qRT-PCR), immunohistochemistry and Western blotting.
      RESULTS: Compared with the control group, IIRI groups presented the thickening of
      alveolar wall, the hemorrhage of alveolar space and the increased W/D ratios
      (P<0.05). qRT-PCR, immunohistochemistry and Western blotting showed that the
      expression of Zc3h12d mRNA and protein significantly decreased (P<0.05) after 120
      minute reperfusion. CONCLUSION: IIRI can down-regulate Zc3h12d gene expression in
      lung tissue, which implies that Zc3h12d protein may protect rats from IIRI
      induced ALI.

PMID- 24721401
TI  - [Early maternal deprivation decreases the immunological function of F1 generation
      offspring in mice].
AB  - OBJECTIVE: To explore the changes of immunological function in F1 generation
      offspring after suffering early maternal deprivation. METHODS: Using Wistar rats,
      the maternal deprivation models were established according to our previous study.
      Their F1 generation offspring were enrolled for this study. The mass and indexes
      of spleen and thymus were measured. The phagocytosis assay was used to detect the
      phagocytic function of peritoneal macrophages. The proliferation of T lymphocytes
      was detected by MTT assay. ELISA was employed to determine the IL-2 level in
      serum. RESULTS: The maternal deprivation decreased the mass and indexes of spleen
      and thymus of their offspring. The phagocytic function of macrophage,
      proliferation of T lymphocytes and IL-2 level in serum of F1 generation offspring
      were also reduced. CONCLUSION: The immunological function declines in F1
      generation offspring after suffering early maternal deprivation in mice.

PMID- 24721402
TI  - [DNA polymerase delta-interacting protein 1 enhances GFP protein degradation].
AB  - OBJECTIVE: To prove whether the over-expression of DNA polymerase delta
      interacting protein 1 (PDIP1) protein can promote the degradation of exogenous
      GFP protein. METHODS: The plasmids of pEGFP-C3 and pCMV-myc-PDIP1 were co
      transfected into HEK293 cells. The fluorescence intensity of the transfected
      cells was analyzed using fluorescence microscope. The expressions of GFP and
      PDIP1 were measured by Western blotting. Then, the expressions of GFP and PDIP1
      were again detected in the cells which were treated by ammonium chloride or
      MG132, respectively. RESULTS: Compared with the ones transfected with pEGFP-C3
      along, green fluorescence intensity of HEK293 cells transfected with the plasmids
      of pEGFP-C3 and pCMV-myc-PDIP1 was lower, and GFP level decreased as the
      expression of PDIP1 increased. The decreased GFP was significantly alleviated by
      the proteasome inhibitor MG132 treatment, but was not significantly affected by
      ammonium chloride. CONCLUSION: Over-expression of PDIP1 can promote the
      degradation of exogenous GFP, and the degradation might be caused via proteasome
      pathway. Our results suggest that PDIP1 might have a hand in the degradation of
      some proteins in cells.

PMID- 24721403
TI  - [IL-17A promotes pulmonary inflammation in rats with pulmonary fibrosis induced
      by bleomycin].
AB  - OBJECTIVE: To investigate the role of IL-17A in the development of pulmonary
      fibrosis in rats. METHODS: Twenty female Wistar rats were randomly divided into
      normal saline (NS) group and bleomycin (BLM) group. The BLM group was
      intratracheally instilled with BLM, while the NS group was treated with saline
      instead. Half of the rats in each group were sacrificed respectively on day 7 and
      28 after intratracheal instillation. HE and Masson stainings were performed to
      show the pathological changes of lung tissues. The expression of IL-17A in lung
      tissues was detected by the immunohistochemistry. The bronchoalveolar lavage
      fluid (BALF) was harvested; one part of it was used for cell counting and
      classification, and for the detection of the concentration of IL-17A in BALF
      using ELISA; the other part of it was used for determining the concentration of
      IL-17A in the culture supernatant of the purified alveolar macrophage (AM) using
      ELISA and reverse transcription PCR (RT-PCR). RESULTS: Compared with the NS
      group, the BLM group presented a great deal of inflammatory cells in the alveoli,
      the increased total number of cells, decreased AM level and increased neutrophil
      number in BALF on day 7; on day 28, the BLM group had milder alveolitis and more
      serious fibrosis. The expression of IL-17A protein in lung tissues was obviously
      higher on day 7 and 28 in the BLM group than in the NS group (P<0.05), and it was
      higher on day 7 than on day 28. The increased total number of BALF cells in BLM
      group returned to the normal level on day 28. The level of IL-17A in BALF
      increased significantly on day 7 and 28 in BLM group, however, compared with that
      on day 7, it decreased on day 28. Compared to the NS group, the expression of IL
      17A protein in the culture supernatant of the BLM group was remarkably higher at
      12th, 24th and 48th hours (P<0.05). RT-PCR showed that compared with the NS
      group, the expression of IL-17A mRNA increased significantly in BLM group on day
      7 and 28 (P<0.05). CONCLUSION: IL-17A promotes the development of pulmonary
      inflammation, indicating that it may be involved in the progress of pulmonary
      fibrosis.

PMID- 24721404
TI  - [HBx silencing by shRNA down-regulates MMP-2 expression in human hepatocellular
      carcinoma cell HepG2.2.15].
AB  - OBJECTIVE: To observe the effects of HBx shRNA on MMP-2 expression in human
      hepatocellular carcinoma cell HepG2.2.15. METHODS: HepG2.2.15 cells were
      transfected with psiHBV/X plasmid using Lipofectamine(TM);2000. The silencing
      efficacy was evaluated by reverse transcription PCR (RT-PCR) detecting the
      expression of HBx gene. The proliferation of HepG2.2.15 cells was examined by MTT
      assay. The expression levels of MMP-2 mRNA and protein were assayed by real-time
      quantitative PCR (qRT-PCR) and Western blotting, respectively. RESULTS: RT-PCR
      showed that the efficiency of RNA interference of HBx gene was 53.6%. MTT
      detection revealed that the cell proliferation was inhibited at 24, 48, and 72
      hours after the transfection (0.388+/-0.087, 0.623+/-0.016, 0.997+/-0.036) and
      the differences had statistically significance as compared with the control group
      (0.436+/-0.027, 0.731+/-0.017, 1.105+/-0.051) (P<0.05). The qRT-PCR and Western
      blotting showed that the expression of MMP-2 decreased at both mRNA and protein
      levels, and the differences had statistically significance as compared with the
      control group (P<0.05). CONCLUSION: HBx gene RNA interference can inhibit the
      cell proliferation and down-regulate the expression of MMP-2 in HepG2.2.15 cells.

PMID- 24721406
TI  - [Comparison of therapeutic effects of olfactory ensheathing cells derived from
      olfactory mucosa or olfactory bulb on spinal cord injury mouse models].
AB  - OBJECTIVE: To isolate and culture olfactory ensheathing cells from different
      origins, compare their different biological characteristics, and evaluate their
      therapeutic effect on spinal cord injury mouse models. METHODS: The olfactory
      ensheathing cells from olfactory mucosa or olfactory bulb were isolated and
      cultured by differential adhesion method. The expressions of S100 and P75
      proteins were examined by immunofluorescence staining; their growth curves were
      drawn by MTT colorimetric assay; the secretion of neurotrophic factors, brain
      derived neurotrophic factor (BDNF), nerve growth factor (NGF), and neurotrophin-3
      (NT-3) was measured by ELISA; the gene expressions of BDNF, NGF, NT-3,
      neurotrophin-4 (NT-4), growth-associated protein 43 (GAP-43), and microtubule
      associated protein (MAP-2) were quantified by real-time PCR; the therapeutic
      effect on spinal cord injury mouse models was evaluated by Basso, Beattie and
      Bresnahan (BBB) locomotor rating scale, which had been carried out daily for 8
      weeks after the olfactory ensheathing cells of the two different origins were
      respectively grafted to the mouse models. RESULTS: The two types of olfactory
      ensheathing cells showed bipolar or tripolar shape; both of them were S100 and
      P75 protein positive; both of them expressing the gene of BDNF, NGF, NT-3, and NT
      4; the olfactory bulb-derived cells did not express MAP-2, but it highly
      expressed GAP-43 gene; the olfactory mucosa-derived cells displayed a low
      expression of MAP-2 and GAP-43; the growth speed of olfactory bulb-derived cells
      was faster than that of the olfactory mucosa-derived cells. Both of them could
      secrete BDNF, NGF, and NT-3, but the neurotrophic factor levels secreted in the
      olfactory mucosa-derived cells were higher. The daily neurological BBB scoring
      showed that the therapeutic effect of olfactory mucosa-derived cells on spinal
      cord injury mouse models was better than that of the olfactory bulb-derived
      cells. CONCLUSION: There exist biological differences between the olfactory
      mucosa-derived cells and the olfactory bulb-derived cells. The olfactory mucosa
      derived cells showed the better therapeutic effect on spinal cord injury mouse
      models.

PMID- 24721405
TI  - [Protective effect of meloxicam against acute radiation-induced brain injury in
      rats].
AB  - OBJECTIVE To observe the protective effect of meloxicam against acute radiation
      induced brain injury in rats. METHODS: Fifty-four SD rats were randomly divided
      into blank control group, radiation group (20 Gy) and therapy group (20 Gy
      radiation followed by 10 mg/kg meloxicam treatment). The whole brain of SD rats
      in the radiation and therapy groups were vertically irradiated by 6 MeV electron
      beam at a dose of 20 Gy. One, 3 and 7 days after irradiation, the morphological
      changes of hippocampal neurons were observed using HE staining, and the
      expressions of cyclooxygenase-2 (COX-2) mRNA and protein were detected by RT-PCR
      and immunohistochemistry, respectively. RESULTS: Compared with the blank control
      group, the radiation group showed that the neuron swelling and vascular
      endothelial cell edema as well as space enlargement around the capillaries. Both
      neuron swelling and vascular endothelial cell injury in the therapy group were
      slighter than those in the radiation group. Compared with the blank control
      group, the levels of COX-2 mRNA and protein in the radiation and therapy groups
      increased obviously one day after irradiation (P<0.05), and compared with the
      radiation group, the levels decreased obviously in the therapy group (P<0.05); 3
      and 7 days after irradiation, the levels of COX-2 mRNA and protein among the 3
      groups had no statistical differences (P>0.05). CONCLUSION: The early use of
      meloxicam can reduce the brain injury induced by radiation. Its protective effect
      may be related to the relief of vascular endothelial cell injury and the
      decreased expression of COX-2.

PMID- 24721407
TI  - [Erythromycin restores oxidative stress-induced corticosteroid responsiveness of
      human THP-1 cells by up-regulating the expression of histone deacetylase 2].
AB  - OBJECTIVE: To investigate the effect of erythromycin (EM) on corticosteroid
      insensitivity of human THP-1 cells induced by cigarette smoke extract (CSE) and
      its mechanism. METHODS: THP-1 cells were treated with EM followed by CSE
      stimulation. Histone deacetylase-2 (HDAC2) short interference RNA (HDAC2-siRNA)
      was transfected into the cells using Lipofectamine(TM); 2000. Interleukin-8 (IL
      8) level in supernatants was measured by ELISA and HDAC2 expression was
      determined by real-time quantitative PCR (qRT-PCR) and Western blotting. RESULTS:
      The inhibition ratio of IL-8 in the EM group was significantly higher than that
      in the CSE group, but lower than that in the control group (P<0.05). The half
      maximal inhibitory concentration of dexamethasone (IC50;-Dex) in the EM group was
      lower than that in the CSE group, but higher than that in the control group
      (P<0.05). The expression of HDAC2 protein in the EM group was higher than that in
      the CSE group, but lower than that in the control group (P<0.05). Besides, HDAC2
      mRNA and HDAC2 protein expressions were lower in the HDAC2-siRNA group than in
      the scrambled oligonucleotide (SC) group. EM could reverse HDAC2 mRNA and HDAC2
      protein reduction induced by HDAC2-siRNA (P<0.05). CONCLUSION: Corticosteroid
      sensitivity of THP-1 cells could be reduced by CSE. EM could reverse the
      corticosteroid insensitivity by up-regulating the expression of HDAC2 protein.

PMID- 24721408
TI  - [Atorvastatin inhibits cardiomyocyte apoptosis via down-cegulation the expression
      mitofusin 2 after myocardial ischemia/reperfusion injury in rats].
AB  - OBJECTIVE: To investigate the effects of atorvastatin (statin for short) on cell
      apoptosis and the expression of mitofusin 2 (Mfn2) after myocardial
      ischemia/reperfusion (I/R) injury in rats. METHODS: A total of 32 male Sprague
      Dawley rats were randomly divided into sham group, I/R group, statin group 1 and
      group 2, with 8 rats in each group. The rats in the two statin groups were given
      atorvastatin 10 and 40 mg/(kg.d) daily since the 7th day before I/R injury,
      respectively. The rats in the I/R group were given distilled water instead. The
      I/R injury models were induced by the ligation of left anterior descending (LAD)
      artery for 30 minutes followed by recovering the blood stream. Three hours after
      reperfusion, the I/R injured areas of rat hearts were harvested, and
      cardiomyocyte apoptosis was assessed by in situ terminal deoxynucleotidyl
      transferase (TdT)-dUTP nick-end labeling (TUNEL). Immunohistochemistry and
      Western blotting were respectively performed to determine the expressions of Mfn2
      and phosphorylated Akt (p-Akt). RESULTS: Three hours after reperfusion, the
      cardiomyocyte apoptosis and Mfn2 protein expression of the I/R and statin
      treatment groups remarkably increased, and p-Akt expression significantly
      decreased (P<0.01) as compared with those of the sham group. Compared with those
      of the I/R group, cardiomyocyte apoptosis and Mfn2 protein expression of statin
      groups were significantly reduced in a slightly dose-dependent manner (P<0.05),
      and p-Akt expression was obviously raised (P<0.05). CONCLUSION: Atorvastatin can
      suppress cardiomyocyte apoptosis after I/R injury in rats, which may be related
      to the down-regulated expression of Mfn2.

PMID- 24721409
TI  - [The expression of KATP; channel mutant subunit Kir6.2AAA in rat cardiomyocytes].
AB  - OBJECTIVE: To construct a recombinant adenovirus vector carrying KATP; channel
      mutant subunit Kir6.2AAA and express it in rat cardiomyocytes. METHODS: Based on
      the primers for Kir6.2 subunits, Kir6.2 GFG amino acids were site-directed
      mutated into AAA by means of overlap PCR. PCR products were cloned into pShuttle
      vector for sequence analysis. After Pme I linearization, it was transformed into
      adenovirus expression vector pAdEasy-1. Then the pAdEasy-1 was packaged into
      liposome and transfected into primary cultured rat cardiomyocytes. The expression
      of Kir6.2AAA was confirmed by reverse transcription PCR(RT-PCR) and Western
      blotting. RESULTS: The recombinant adenovirus carrying the gene fragment
      Kir6.2AAA and EGFP was constructed successfully, and the virus titer was
      2.64*10(11); VP/mL. After infected by the recombinant adenovirus expressing
      Kir6.2AAA, rat cardiomyocytes expressed EGFP and emitted green fluorescence under
      a fluorescence microscope. RT-PCR demonstrated that the expression of Kir6.2AAA
      was significantly up-regulated in the infected cardiomyocytes, and Western
      blotting also proved the over-expression of Kir6.2AAA in the cardiomyocytes.
      CONCLUSION: The recombinant adenovirus carrying the gene fragment Kir6.2AAA and
      EGFP was constructed successfully and expressed correctly in rat cardiomyocytes.

PMID- 24721410
TI  - [Preparation and identification of the polyclonal antibody against GAPDH protein
      from Shigella flexneri M90T].
AB  - OBJECTIVE: To prepare mouse polyclonal antibodies against Shigella flexneri M90T
      glyceraldehyde-3-phosphate dehydrogenase (GAPDH), and verify its titer and
      specificity. METHODS: The gapA gene of Shigella flexneri M90T was amplified by
      PCR from extracted genomic DNA and inserted into expression vector pET24a. The
      plasmid pET24a-gapA was transformed into E.coli BL21(DE3) and induced to express
      the tagged protein GAPDH-His. After condition optimization, the protein was
      purified with Ni Sepharose(TM); 6 Fast Flow. The polyclonal antibodies were
      prepared by immunizing the mice with the purified recombinant protein and then
      harvesting mouse sera. The specificity and efficiency of antibodies in sera were
      analyzed by Western blotting and ELISA against whole cell proteins of Shigella
      flexneri M90T. RESULTS: The recombinant plasmid pET24a-gapA was successfully
      constructed. The soluble expression of the tagged protein GAPDH-His was achieved
      with 2-hour induction of 1 mmol/L IPTG at 30 degrees C. Western blotting and
      ELISA demonstrated that the polyclonal antibody harvested from the mice immunized
      with GAPDH-His was specific and efficient against Shigella flexneri M90T GAPDH.
      Conclusion The mouse polyclonal antibodies against the Shigella flexneri M90T
      GAPDH protein were successfully prepared.

PMID- 24721411
TI  - [Significance of SAMD9 expression in esophageal squamous cell carcinoma].
AB  - OBJECTIVE: To analyze the significance of sterile alpha motif domain-containing 9
      (SAMD9) expression in esophageal squamous cell carcinoma (ESCC). METHODS:
      Immunohistochemical staining was performed to detect the expression of SAMD9 in
      72 primary ESCC and matched adjacent cancer-free tissues and analyze the
      significance of SAMD9 expression in ESCC tissues. In addition, Western blotting
      was used to detect the expression of SAMD9 in primary ESCC tissues which were
      taken from 3 metastatic and 3 non-metastatic patients during surgery. RESULTS:
      The expression of SAMD9 in the ESCC tissues had no statistical difference from
      that in the matched adjacent cancer-free tissues. SAMD9 expression was
      significantly correlated with lymphatic invasion and metastasis in these patients
      (P<0.05), but not with age, gender, tumor differentiation and T stage (P>0.05).
      Western blotting showed that SAMD9 expression in primary ESCC tissues was
      significantly higher in the patients with metastasis than in the ones without
      metastasis(P<0.01). CONCLUSION: Over-expression of SAMD9 is correlated with the
      metastasis of ESCC, indicating that it might play an important role in the
      metastasis of ESCC.

PMID- 24721412
TI  - [Detection of intracellular HIV-1 p24 antigen in CD4(+);T cells by flow cytometry
      and its application for auxiliary diagnosis of HIV-1 infection].
AB  - OBJECTIVE: To detect the human immunodeficiency virus 1 (HIV-1) p24 antigen in
      CD4(+);T cells by flow cytometry (FCM) and assess its application for auxiliary
      diagnosis of HIV-1 infection. METHODS: CD4(+);T cells from HIV-1-infected
      individuals and normal controls (negative controls) were detected for
      intracellular p24 antigen by FCM. Samples from early-HIV-infected individuals
      were collected, and the intracellular p24 antigen in CD4(+);T cells was detected
      by FCM. P24 antigen in plasma was detected by ELISA and nucleic acids were tested
      by nest-PCR. The results of these 3 assays were compared. RESULTS: The rates of
      p24(+);CD4(+);T cells of the infected individuals were significantly higher than
      those of the negative controls (P<0.01); the 95th percentile of p24(+);CD4(+);T
      cell rates of the infected individuals was 1.92% and the cutoff value was 2.00%.
      Infected individuals with CD4(+);T <=350 cells/MUL had higher p24(+);CD4(+);T
      cell rates than those with CD4(+);T >350 cells/MUL (P<0.05). The detection of p24
      antigen in CD4(+);T cells of early-HIV-1-infected patients could identify HIV-1
      infection timely, and the detection efficiency of FCM was better than that of the
      ELISA of p24 antigen in plasma and was equal to that of nucleic acid testing.
      CONCLUSION: The FCM detection of p24 antigen in CD4(+);T cells could be a
      promising auxiliary approach for the diagnosis of early HIV-1 infection.

PMID- 24721413
TI  - Paddy field--a natural sequential anaerobic-aerobic bioreactor for
      polychlorinated biphenyls transformation.
AB  - The environmental pollution and health risks caused by the improper disposal of
      electric and electronic waste (e-waste) have become urgent issues for the
      developing countries. One of the typical pollutants, polychlorinated biphenyls
      (PCBs), is commonly found in farmland in Taizhou, a major hotspot of e-waste
      recycling in China. This study investigated the amount of PCB residue in local
      farmlands. Biotransformation of PCBs was further studied under different water
      management conditions in paddy field with or without rice cultivation, with a
      special focus on the alternating flooded and drying processes. It was found that
      paddy field improved the attenuation of PCBs, especially for highly chlorinated
      congeners. In the microcosm experiment, 40% or more of the initial total PCBs was
      removed after sequential flood-drying treatments, compared to less than 10% in
      the sterilized control and 20% in the constant-drying system. Variation in the
      quantity of PCBs degrading and dechlorinating bacterial groups were closely
      related to the alteration of anaerobic-aerobic conditions. These results
      suggested that alternating anoxic-oxic environment in paddy field led to the
      sequential aerobic-anaerobic transformation of PCBs, which provided a favorable
      environment for natural PCB attenuation. 

PMID- 24721414
TI  - [Acute cough in infants: impact of national guidelines on medical practices in a
      French department].
AB  - CONTEXT AND AIM: Guidelines have been published regularly since 2010 by the ANSM
      (the Health Products Safety Agency) advising against antitussive drugs for
      infants because of their inefficacy and their side effects (convulsions,
      respiratory congestion). Antihistamines, mucolytics, and terpene-based
      suppositories have theoretically disappeared from infant pharmacopoeia. We
      assessed the degree of compliance with these guidelines on the part of health
      professionals. MATERIALS AND METHODS: From June 2012 to August 2012, 198 general
      practitioners and 44 pediatricians were assessed in the Alpes-Maritimes
      department of France by means of questionnaires. At the same time, an analysis of
      medical prescriptions was sought from the Regional Directorate of Medical
      Services (RDMS) of the PACA-Corse region Health Insurance. RESULTS: The rate of
      noncompliance with the contraindications was 14.9% (17.7% general practitioners
      and 2.3% pediatricians). The RDMS study showed a slight decrease in prescriptions
      for antitussives not recommended from 2011 to 2012: -21% for pediatricians, 
      15.5% for generalist physicians. CONCLUSION: Continued educational and
      informative campaigns are therefore needed to stop medical prescriptions of cough
      medicines for infants, which should also involve parents.

PMID- 24721415
TI  - [Anterolateral diaphragmatic hernia: case report].
AB  - Congenital anterolateral diaphragmatic hernia is rare, with few cases reported in
      the literature. This anomaly is usually associated with left pulmonary
      hypoplasia. Treatment is surgical and prognosis depends on the presence and
      severity of associated malformations. We report a case of an intraoperative
      discovery of this unusual type of diaphragmatic hernia in an infant. 

PMID- 24721416
TI  - Chest physical therapy in infant acute viral bronchiolitis: should we really
      surrender?

PMID- 24721417
TI  - [BCG vaccination: survey among children less than 5 years of age in an emergency
      department].
AB  - France is a country with a low incidence of tuberculosis. However, there are
      important local variations: some parts of the city of Marseilles (southern
      France) presented a yearly incidence greater than 30/100,000 in 2010. The main
      goal of this study was to evaluate the BCG vaccine coverage among at-risk
      children younger than 5 years consulting in one of the city's pediatric emergency
      departments. MATERIAL AND METHODS: This descriptive study took place in February
      2013 and used a semi-directive questionnaire distributed to parents. RESULTS: One
      hundred and thirty-five children were included, 98 (72.6 %) were considered as
      being at risk of tuberculosis and among them 75 (76.5 %, 95 % CI [68.0-85.1])
      were vaccinated with BCG. Parents' knowledge of tuberculosis was relevant in 48 %
      of the respondents. Only 19 % of the parents reported that BCG protects against
      tuberculosis, but 73 % were in favor of this vaccination. Two criteria
      significantly increased vaccine coverage among at-risk children: birth in
      Marseilles and age more than 6 months on the consultation day. The child living
      in a poor family and type of medical follow-up did not significantly influence
      BCG vaccine coverage. CONCLUSION: BCG coverage was high in at-risk children
      younger than 5 years born in Marseilles. Cooperation between private physicians,
      maternity hospitals and mothers, and children's public health services probably
      facilitates this high level of protection.

PMID- 24721418
TI  - Rusting the pipes: ingestion of oxidized lipids and vascular disease.

PMID- 24721419
TI  - Effects of a biologic agent in a patient with rheumatoid arthritis after
      treatment for methotrexate-associated B-cell lymphoma: a case report.
AB  - BACKGROUND: Several studies have suggested an increased risk of malignant tumor
      in patients with rheumatoid arthritis. It has been also reported that rheumatoid
      arthritis patients have a high incidence of lymphoma compared with the general
      population, and that patients receiving methotrexate, which is the anchor drug
      for rheumatoid arthritis treatment, can develop lymphoproliferative disease.
      Nevertheless, management of rheumatoid arthritis after treatment for methotrexate
      associated lymphoma has not been fully investigated. We here report a patient
      with rheumatoid arthritis who developed malignant lymphoma associated with
      methotrexate therapy. Moreover, we describe the use of a biologic agent for a
      rheumatoid arthritis patient after treatment for lymphoma associated with
      methotrexate. CASE PRESENTATION: A 60-year-old Japanese man with a 20-year
      history of rheumatoid arthritis was admitted to our hospital with a left inguinal
      tumor. Open biopsy was performed and a biopsy specimen revealed diffuse large B
      cell lymphoma. As our patient had received methotrexate for 4 years, we diagnosed
      the lymphoproliferative disease as being methotrexate-related. This lymphoma was
      not associated with Epstein- Barr virus by Epstein-Barr virus-encoded ribonucleic
      acid in-situ hybridization, but this patient was an Epstein-Barr virus carrier,
      regarding serological testing. The lymphoma went into complete remission after 6
      courses of rituximab plus cyclophosphamide, hydroxydaunorubicin, vincristine, and
      prednisone/prednisolone therapy. Two years later, however, rheumatoid arthritis
      activity gradually increased and was not controlled with salazosulfapyridine.
      Etanercept was administered in view of its possible effect on B-cells, and this
      reduced the level of disease activity without recurrence of lymphoma. CONCLUSION:
      The management of rheumatoid arthritis after treatment for methotrexate
      associated lymphoma has not been fully investigated yet. Etanercept appeared to
      be safe because of its B-cell effect, but further observation is necessary to
      make a firm conclusion. Further accumulation of cases is needed to clarify which
      biologics are safe and effective for treatment of methotrexate-associated B-cell
      lymphoma.

PMID- 24721421
TI  - Evaluation of methods of detecting cell reactive oxygen species production for
      drug screening and cell cycle studies.
AB  - Intracellular reactive oxygen species (ROS) production is essential to normal
      cell function. However, excessive ROS production causes oxidative damage and cell
      death. Many pharmacological compounds exert their effects on cell cycle
      progression by changing intracellular redox state and in many cases cause
      oxidative damage leading to drug cytotoxicity. Appropriate measurement of
      intracellular ROS levels during cell cycle progression is therefore crucial in
      understanding redox-regulation of cell function and drug toxicity and for the
      development of new drugs. However, due to the extremely short half-life of ROS,
      measuring the changes in intracellular ROS levels during a particular phase of
      cell cycle for drug intervention can be challenging. In this article, we have
      provided updated information on the rationale, the applications, the advantages
      and limitations of common methods for screening drug effects on intracellular ROS
      production linked to cell cycle study. Our aim is to facilitate biomedical
      scientists and researchers in the pharmaceutical industry in choosing or
      developing specific experimental regimens to suit their research needs. 

PMID- 24721420
TI  - Comparison of freely-moving telemetry Chinese Miniature Experiment Pigs (CMEPs)
      to beagle dogs in cardiovascular safety pharmacology studies.
AB  - INTRODUCTION: Telemetry beagle dogs are the most frequently used species in
      cardiovascular telemetry assessments. However, beagle dogs may not be always
      suitable for all of the tests. Recently minipigs have received increased
      attention for these studies. Differences between the two species regarding the
      response of their cardiovascular systems to environmental stimuli are unclear.
      This study investigates how the telemetry minipig compares to beagle dog as a
      test subject and also refines the experimental protocols necessary to obtain
      accurate data. METHODS: Beagle dogs and Chinese Miniature Experiment Pigs (CMEPs)
      were implanted with telemetry transmitters and the influences of gavage, feeding
      and the circadian cycle on various cardiovascular parameters were investigated.
      RESULTS: ECG signal quality from CMEPs was superior to that of the beagle dogs.
      Poor ECG signal quality, elevated HR, BP and locomotor activity associated with
      gavage and feeding were observed in both species. ECG signal quality, BP and
      locomotor activity recovered more quickly in the CMEPs than in the beagle dogs.
      Residual elevation of HR found in CMEPs lasted approximately 4h post-feeding,
      which has a profound influence on the circadian cycle. A diurnal rhythm in CMEP
      with a significant increase of body temperature during the dark period and a
      clear circadian rhythm of locomotor activity in both species were observed.
      DISCUSSION: The present data demonstrated that gavage, feeding and circadian
      cycle were having an enormous influence on BP, HR and locomotor activity in both
      species. If drug-induced effects are expected rapidly after oral administration
      and feeding, CMEP seems to be a favorable choice. Also, due to the effects of
      feeding on HR, CMEPs should fast at least 5h before the start of recording or
      should not be fed during the study where the Tmax of a given compound might occur
      very late. It also should be taken into consideration when the test article has a
      potential effect on body temperature by using CMEPs. In summary, the telemetry
      CMEP is a valuable alternative to the beagle dog for cardiovascular telemetry
      studies.

PMID- 24721422
TI  - Retention rates of adalimumab, etanercept and infliximab as first and second-line
      biotherapy in patients with rheumatoid arthritis in daily practice.
AB  - OBJECTIVES: To compare retention rates of adalimumab, etanercept and infliximab
      as first-line biotherapy in rheumatoid arthritis (RA), to determine causes of
      discontinuation, retention-associated factors, and retention rates of possible
      second-line TNF-alpha inhibitors (TNFi). METHODS: In this retrolective,
      multicentric study, medical charts of RA patients starting TNFi between March
      2005 and April 2009 were reviewed, with follow-up between two and six years. The
      retention rate was estimated using the Kaplan-Meier method. Comparison between
      TNFi was done after adjustment using a Cox model. Factors associated with better
      retention were identified by multivariate analysis. RESULTS: Of the 706 patients
      included, the percentage continuing treatment after two years was 54.9, 61.9 and
      48.7%, and the median retention was 31, 45 and 23 months for adalimumab,
      etanercept and infliximab, respectively. The hazard ratios (HRs) for
      discontinuation were greater with adalimumab and infliximab than etanercept
      (1.315, 95% CI [1.050-1.648] and 1.380, 95% CI [1.041-1.828], respectively). The
      HR for discontinuation due to inefficacy was significantly higher with adalimumab
      than etanercept. Adverse events were significantly higher with infliximab than
      etanercept. Past use of more DMARDs and higher baseline ESR were associated with
      better retention. The median retention of the second-line TNFi was 11, 43 and
      19.1 months for adalimumab, etanercept, and infliximab, respectively. HRs for
      adalimumab discontinuation due to all causes were significantly greater than for
      etanercept. CONCLUSIONS: Etanercept had a better retention rate than adalimumab
      and infliximab as first-line biotherapy in RA, and than adalimumab as second-line
      biotherapy.

PMID- 24721423
TI  - Liquid crystal and gold nanoparticles applied to electrochemical immunosensor for
      cardiac biomarker.
AB  - A label-free electrochemical immunosensor based on the ionic liquid crystal (E)-1
      decyl-4-[(4-decyloxyphenyl)diazenyl]pyridinium bromide (Br-Py) coated on a glassy
      carbon electrode (GCE) for the quantitative detection of myoglobin (Mb), a
      cardiac marker for acute myocardial infarction, is reported herein for the first
      time. The monoclonal anti-myoglobin antibody (ab-Mb) was covalently immobilized
      using glyoxal on a film of polyethyleneimine-coated gold nanoparticles (AuNP
      PEI). The proposed method for Mb detection is based on voltammetric suppression
      of the Br-Py signal when the immunosensor was incubated with Mb antigen. The
      electrochemical performance of the Mb immunosensor was studied by electrochemical
      impedance spectroscopy, and cyclic and square-wave voltammetry. Under the optimal
      conditions, the proposed immunosensor shows a good linear relationship between
      the electrochemical inhibition response and the concentration of Mb over the
      range of 9.96-72.8 ng mL(-1) with a detection limit of 6.29 ng mL(-1). The
      results obtained indicate that the proposed immunosensor provides good
      sensitivity and simple operation for detecting acute myocardial infarction with
      Mb as a biomarker.

PMID- 24721424
TI  - Electrochemical enzymeless detection of superoxide employing naringin-copper
      decorated electrodes.
AB  - Flavonoid-metal ion complexes are a new class of molecules that have generated
      considerable interest due to their superior anti-oxidant and pharmacological
      activities. The metal ion present in these complexes can participate in redox
      reactions by toggling between different oxidation states. This property can be
      invaluable for sensing applications. But, the use of flavonoid-metal ion
      complexes as sensors remains an unexplored facet. The present work attempts to
      develop a non-enzymatic superoxide sensor using naringin-copper complex.
      Detection of superoxide has been mainly based on enzymes and cytochromes.
      However, these sensors are limited by their poor structural stability and high
      cost. The naringin-copper based non-enzymatic sensor exhibits good sensitivity in
      a range of 0.2-4.2 uM with a response time of <1 s. The performance of the sensor
      is not affected by pH and common interferents.

PMID- 24721425
TI  - Mitochondrial impairment observed in fibroblasts from South African Parkinson's
      disease patients with parkin mutations.
AB  - Parkinson's disease (PD), defined as a neurodegenerative disorder, is
      characterized by the loss of dopaminergic neurons in the substantia nigra in the
      midbrain. Loss-of-function mutations in the parkin gene are a major cause of
      autosomal recessive, early-onset PD. Parkin has been implicated in the
      maintenance of healthy mitochondria, although previous studies show conflicting
      findings regarding mitochondrial abnormalities in fibroblasts from patients
      harboring parkin-null mutations. The aim of the present study was to determine
      whether South African PD patients with parkin mutations exhibit evidence for
      mitochondrial dysfunction. Fibroblasts were cultured from skin biopsies obtained
      from three patients with homozygous parkin-null mutations, two heterozygous
      mutation carriers and two wild-type controls. Muscle biopsies were obtained from
      two of the patients. The muscle fibers showed subtle abnormalities such as
      slightly swollen mitochondria in focal areas of the fibers and some folding of
      the sarcolemma. Although no differences in the degree of mitochondrial network
      branching were found in the fibroblasts, ultrastructural abnormalities were
      observed including the presence of electron-dense vacuoles. Moreover, decreased
      ATP levels which are consistent with mitochondrial dysfunction were observed in
      the patients' fibroblasts compared to controls. Remarkably, these defects did not
      manifest in one patient, which may be due to possible compensatory mechanisms.
      These results suggest that parkin-null patients exhibit features of mitochondrial
      dysfunction. Involvement of mitochondria as a key role player in PD pathogenesis
      will have important implications for the design of new and more effective
      therapies. 

PMID- 24721426
TI  - Cell cycle arrest and activation of development in marine invertebrate
      deuterostomes.
AB  - Like most metazoans, eggs of echinoderms and tunicates (marine deuterostomes,
      there is no data for the cephalochordates) arrest awaiting fertilization due to
      the activity of the Mos/MEK/MAPK cascade and are released from this cell cycle
      arrest by sperm-triggered Ca2+ signals. Invertebrate deuterostome eggs display
      mainly three distinct types of cell cycle arrest before fertilization mediated by
      potentially different cytostatic factors (CSF): one CSF causes arrest during
      meiotic metaphase I (MI-CSF in tunicates and some starfishes), another CSF likely
      causes arrest during meiotic metaphase II (amphioxus), and yet another form of
      CSF causes arrest to occur after meiotic exit during G1 of the first mitotic
      cycle (G1-CSF). In tunicates and echinoderms these different CSF activities have
      been shown to rely on the Mos//MAPK pathway for establishment and on Ca2+ signals
      for their inactivation. Despite these molecular similarities, release of MI-CSF
      arrest is caused by APC/C activation (to destroy cyclin B) whereas release from
      G1-CSF is caused by stimulating S phase and the synthesis of cyclins. Further
      research is needed to understand how both the Mos//MAPK cascade and Ca2+ achieve
      these tasks in different marine invertebrate deuterostomes. Another conserved
      feature of eggs is that protein synthesis of specific mRNAs is necessary to
      proceed through oocyte maturation and to maintain CSF-induced cell cycle arrest.
      Then activation of development at fertilization is accompanied by an increase in
      the rate of protein synthesis but the mechanisms involved are still largely
      unknown in most of the marine deuterostomes. How the sperm-triggered Ca2+ signals
      cause an increase in protein synthesis has been studied mainly in sea urchin
      eggs. Here we review these conserved features of eggs (arrest, activation and
      protein synthesis) focusing on the non-vertebrate deuterostomes. 

PMID- 24721427
TI  - Calcium signaling and endoplasmic reticulum dynamics during fertilization in
      marine protostome worms belonging to the phylum Nemertea.
AB  - Metaphase-I-arrested eggs of marine protostome worms in the phylum Nemertea
      generate a series of point-source calcium waves during fertilization. Such
      calcium oscillations depend on inositol-1,4,5-trisphosphate-mediated calcium
      release from endoplasmic reticulum (ER) stores that undergo structural
      reorganizations prior to and after fertilization. This article reviews
      fertilization-induced calcium transients and ER dynamics in nemertean eggs and
      compares these topics to what has been reported for other animals in order to
      identify unifying characteristics and distinguishing features of calcium
      responses during fertilization across the animal kingdom. 

PMID- 24721428
TI  - CMTM5 exhibits tumor suppressor activity through promoter methylation in oral
      squamous cell carcinoma.
AB  - Oral squamous cell carcinoma (OSCC) is one of the most common types of
      malignancies in the head and neck region. CKLF-like MARVEL transmembrane domain
      containing member 5 (CMTM5) has been recently implicated as a tumor suppressor
      gene in several cancer types. Herein, we examined the expression and function of
      CMTM5 in oral squamous cell carcinoma. CMTM5 was down-regulated in oral squamous
      cell lines and tumor samples from patients with promoter methylation. Treatment
      with the demethylating agent 5-aza-2'-deoxycytidine restored CMTM5 expression. In
      the OSCC cell lines CAL27 and GNM, the ectopic expression of CMTM5-v1 strongly
      inhibited cell proliferation and migration and induced apoptosis. In addition,
      CMTM5-v1 inhibited tumor formation in vivo. Therefore, CMTM5 might act as a
      putative tumor suppressor gene through promoter methylation in oral squamous cell
      carcinoma. 

PMID- 24721430
TI  - Is the idea of a fast block to polyspermy based on artifact?
AB  - This purpose of this review is to look at the experimental evidence, both kinetic
      and electrophysiological, that led to the hypothesis of a fast electrical block
      to polyspermy in sea urchin eggs. The idea of a fast partial block, forwarded in
      the 1950's, that would reduce the receptivity of the egg surface by 1/20th
      following its interaction with the fertilizing spermatozoon, was based on
      experiments that treated fertilization as a first order chemical reaction. Here,
      I outline the criticisms of the Rothschild theory and demonstrate that the
      hypothesis of a fast partial block to polyspermy is unfounded. Notwithstanding,
      it was suggested in the 1970's that the membrane depolarization, induced by the
      fertilizing spermatozoon, prevented the interaction of supernumerary spermatozoa,
      the fast electrical block to polyspermy. While trans-membrane voltage recording
      has permitted a better understanding of the sequence of events occurring at
      fertilization, there is no evidence that depolarization prevents the interaction
      of supernumerary spermatozoa. Sperm entry is prevented at positive and negative
      potentials, in the voltage clamp configuration, however this is an artifact
      caused by the currents injected into the egg employed to hold the voltage
      constant in a non-physiological range. At permissive voltages, around -20 mV,
      where the current required to hold the voltage is minimal, only one spermatozoon
      normally enters the egg. Thus, irrespective of the egg voltage, the fertilizing
      spermatozoon is, in any case, attached to a privileged interaction site that
      permits entry and distinguishes it from supernumerary spermatozoa. Competence for
      monospermy is acquired during oocyte maturation and data on cortical organization
      in echinoderm eggs points to the actin filament system for regulating sperm
      entry.

PMID- 24721429
TI  - D-Alanine in the islets of Langerhans of rat pancreas.
AB  - Relatively high levels of D-alanine (D-Ala), an endogenous D-amino acid, have
      been found in the endocrine systems of several animals, especially in the
      anterior pituitary; however, its functional importance remains largely unknown.
      We observed D-Ala in islets of Langerhans isolated from rat pancreas in
      significantly higher levels than in the anterior/intermediate pituitary;
      specifically, 180+/-60 fmol D-Ala per islet (300+/-100 nmol/gislet), and 10+/-2.5
      nmol/g of wet tissue in pituitary. Additionally, 12+/-5% of the free Ala in the
      islets was in the d form, almost an order of magnitude higher than the percentage
      of D-Ala found in the pituitary. Surprisingly, glucose stimulation of the islets
      resulted in D-Ala release of 0.6+/-0.5 fmol per islet. As D-Ala is stored in
      islets and released in response to changes in extracellular glucose, D-Ala may
      have a hormonal role.

PMID- 24721431
TI  - Androgen-independent proliferation of LNCaP prostate cancer cells infected by
      xenotropic murine leukemia virus-related virus.
AB  - Xenotropic murine leukemia virus-related virus (XMRV) is a novel gammaretrovirus
      that was originally isolated from human prostate cancer. It is now believed that
      XMRV is not the etiologic agent of prostate cancer. An analysis of murine
      leukemia virus (MLV) infection in various human cell lines revealed that prostate
      cancer cell lines are preferentially infected by XMRV, and this suggested that
      XMRV infection may confer some sort of growth advantage to prostate cancer cell
      lines. To examine this hypothesis, androgen-dependent LNCaP cells were infected
      with XMRV and tested for changes in certain cell growth properties. We found that
      XMRV-infected LNCaP cells can proliferate in the absence of the androgen
      dihydrotestosterone. Moreover, androgen receptor expression is significantly
      reduced in XMRV-infected LNCaP cells. Such alterations were not observed in
      uninfected and amphotropic MLV-infected LNCaP cells. This finding explains why
      prostate cancer cell lines are preferentially infected with XMRV.

PMID- 24721432
TI  - Hemostasis in liver disease: implications of new concepts for perioperative
      management.
AB  - The hemostatic profile of patients with liver diseases is frequently profoundly
      different from that of healthy individuals. These complex alterations lead to
      abnormal results from routine laboratory tests, but because of the nature of
      these assays, they fail to accurately represent the patient's hemostatic state.
      Nevertheless, based on abnormal laboratory coagulation values, it has long been
      assumed that patients with liver disease have a natural bleeding tendency and are
      protected from thrombosis. This assumption is false; the average patient with
      liver disease is actually in a state of "rebalanced hemostasis" that can
      relatively easily be tipped toward both bleeding and thrombosis. The new paradigm
      of rebalanced hemostasis has strong implications for the clinic, which are
      presented in this review. There is no evidence that prophylactic transfusion of
      plasma helps to prevent procedure-related bleeding. In addition, the presence of
      independent risk factors such as poor kidney status or infections should be
      carefully assessed before invasive procedures. Furthermore, central venous
      pressure plays an important role in the risk of bleeding in patients with liver
      diseases, so during procedures, a restrictive infusion policy should be applied.
      Finally, thrombosis prophylaxis should not be withheld from patients with
      cirrhosis or acute liver failure, and clinicians should be alert to the
      possibility of thrombosis occurring in these patients. 

PMID- 24721433
TI  - Dietary L-methionine supplementation mitigates gamma-radiation induced global DNA
      hypomethylation: enhanced metabolic flux towards S-adenosyl-L-methionine (SAM)
      biosynthesis increases genomic methylation potential.
AB  - The objective of this study was to examine the effect of (60)Co-gamma (gamma)
      radiation on modulation of genomic DNA methylation, if any, of mice maintained (6
      weeks) on normal control diet (NCD) and L-methionine supplemented diet (MSD). To
      elucidate the possible underlying mechanism(s), we exposed the animals to gamma
      radiation (2, 3 and 4 Gy) and investigated the profile of downstream metabolites
      and enzymes involved in S-adenosyl-L-methionine (SAM) generation. Liver samples
      were also subjected to histopathological examinations. Compared to NCD fed and
      irradiated animals, hepatic folate, choline and L-methionine levels decreased
      moderately, while hepatic SAM levels increased in MSD fed and irradiated animals.
      Under these conditions, a marked modulation of methionine adenosyltransferase
      (MAT) and L-methionine synthase (MSase) activities was observed. Concomitant with
      increase in liver SAM pool, increased DNA methyltransferase (dnmt) activity in
      MSD fed mice indicated enhanced metabolic flux towards DNA methylation. Further
      results showed that genomic DNA methylation and 5-methyl-2'-deoxy cytidine
      residues were maintained at normal levels in MSD fed and irradiated mice compared
      to NCD fed and irradiated animals. In conclusion, our results suggest that
      increasing supply of preformed methyl groups, via dietary L-methionine
      supplementation might significantly increase methylation potential of radiation
      stress compromised DNA methylation cycle.

PMID- 24721434
TI  - Assessment of micronuclei and sister chromatid exchange frequency in the
      petroleum industry workers in province of Vojvodina, Republic of Serbia.
AB  - Persons who work with petroleum and petroleum derivatives (PPD) are potentially
      at risk of developing cancer mostly due to the carcinogenity of benzene.
      Therefore, the aim of this study was to determine in which degree occupational
      exposure of workers to PPD causes damage to DNA by analysis of micronuclei (MN),
      sister chromatid exchanges (SCE) and proliferation index (PI). 30 workers of
      refinery in Novi Sad, participated in the study as exposed and 30 volunteers as
      control group. Workers exposed to PPD had significantly higher values of MN and
      SCE in comparison to controls. Exposition time to PPD and type of working place
      have also significantly effects to DNA damage. The influence of confounding
      factor such as smoking and age were also evaluated. 

PMID- 24721435
TI  - Population impact of a high cardiovascular risk management program delivered by
      village doctors in rural China: design and rationale of a large, cluster
      randomized controlled trial.
AB  - BACKGROUND: The high-risk strategy has been proven effective in preventing
      cardiovascular disease; however, the population benefits from these interventions
      remain unknown. This study aims to assess, at the population level, the effects
      of an evidence-based high cardiovascular risk management program delivered by
      village doctors in rural China. METHODS: The study will employ a cluster
      randomized controlled trial in which a total of 120 villages in five northern
      provinces of China, will be assigned to either intervention (60 villages) or
      control (60 villages). Village doctors in intervention villages will be trained
      to implement a simple evidence-based management program designed to identify,
      treat and follow-up as many as possible individuals at high-risk of
      cardiovascular disease in the village. The intervention will also include
      performance feedback as well as a performance-based incentive payment scheme and
      will last for 2 years. We will draw two different (independent) random samples,
      before and after the intervention, 20 men aged>=50 years and 20 women aged>=60
      years from each village in each sample and a total of 9,600 participants from 2
      samples to measure the study outcomes at the population level. The primary
      outcome will be the pre-post difference in mean systolic blood pressure, analyzed
      with a generalized estimating equations extension of linear regression model to
      account for cluster effect. Secondary outcomes will include monthly clinic
      visits, provision of lifestyle advice, use of antihypertensive medications and
      use of aspirin. Process and economic evaluations will also be conducted.
      DISCUSSION: This trial will be the first implementation trial in the world to
      evaluate the population impact of the high-risk strategy in prevention and
      control of cardiovascular disease. The results are expected to provide important
      information (effectiveness, cost-effectiveness, feasibility and acceptability) to
      guide policy making for rural China as well as other resource-limited countries.
      TRIAL REGISTRATION: The trial is registered at ClinicalTrials.gov (NCT01259700).
      Date of initial registration is December 13, 2010.

PMID- 24721436
TI  - A possible mechanism in the recruitment of eosinophils and Th2 cells through
      CD163(+) M2 macrophages in the lesional skin of eosinophilic cellulitis.
AB  - BACKGROUND: M2 macrophages play a critical role in the recruitment of T helper 2
      (Th2) regulatory T cells (Treg). OBJECTIVES: To study the role of M2 macrophages
      and Treg cells in eosinophilic celulitis. MATERIAL AND METHODS: We employed
      immunohistochemical staining for CD163( )and CD206 (macrophages) as well as FoxP3
      (Treg), in lesional skin of four cases of eosinophilic cellulitis. RESULTS:
      CD163(+) CD206(+) M2 macrophages, which were previously reported to produce CCL17
      to induce Th2 cells and Treg cells, were predominantly infiltrating the
      subcutaneous tissues and interstitial area of the dermis. M2 macrophages derived
      from PBMC showed significantly increased expression of CCL11, CCL17, CCL24 and
      CCL26 mRNA and production of CCL17 and CCL24, when stimulated by IL-4 or IL- 13.
      In addition, CCL17-producing cells and CCL24-producing cells were prominent in
      the lesional skin of EC. CONCLUSION: Our study sheds light on one of the possible
      immunological mechanisms of eosinophilic cellulitis.

PMID- 24721438
TI  - Editorial comment.

PMID- 24721439
TI  - Editorial comment.

PMID- 24721440
TI  - Preparation of low shrinkage methacrylate-based resin system without Bisphenol A
      structure by using a synthesized dendritic macromer (G-IEMA).
AB  - With the growing attention on estrogenic effect of Bisphenol A (BPA), the
      application of BPA derivatives like Bis-GMA in dental materials has also been
      doubted. In this research, new BPA free dental resin systems were prepared with
      synthesized dendritic macromer G-IEMA, UDMA, and TEGDMA. Physicochemical
      properties, such as double bond conversion, polymerization shrinkage, flexural
      strength and modulus, fracture energy, water sorption and solubility of BPA free
      resin formulations were investigated. Bis-GMA/TEGDMA resin system was used as a
      control. Results showed that the prepared BPA free resins could have higher
      double bond conversion, comparable or lower polymerization shrinkage and water
      sorption, and lower water solubility, when compared with Bis-GMA/TEGDMA resin.
      Though flexural strength and modulus of prepared BPA free polymers were lower
      than those of Bis-GMA/TEGDMA polymer, BPA free polymers had higher fracture
      energies and showed plastic deformation prior to fracture, all of these two
      phenomena showed that BPA free polymers in this research might have higher
      fracture toughness which would be good for the service life of dental materials. 

PMID- 24721441
TI  - Investigation of a putative melanoma susceptibility locus at chromosome 3q29.
AB  - Malignant melanoma, the most fatal form of skin cancer, is currently increasing
      in incidence in many populations. Approximately 10% of all cases occur in
      families with an inherited predisposition for melanoma. In Sweden, only a minor
      portion of such melanoma families carry a mutation in the known melanoma gene
      CDKN2A, and there is a need to identify additional melanoma susceptibility genes.
      In a recently performed genome-wide linkage screen, novel loci with suggestive
      evidence of linkage to melanoma were detected. In this study, we have further
      analyzed one region on chromosome 3q29. In all, 89 affected and 15 nonaffected
      family members from 42 melanoma-prone families were genotyped for 34 genetic
      markers. In a pooled linkage analysis of all 42 families, we detected significant
      evidence of linkage, with a maximum heterogeneity logarithm of odds (HLOD) score
      of 3.1 with 83% of the families contributing to the linkage score. The minimum
      critical region of linkage (defined by a 1LOD score support interval) maps to
      chromosome 3q29, spans 3.5 Mb of genomic sequence, and harbors 44 identified
      genes. Sequence variants within this region have previously been associated with
      cancer susceptibility. This study reports the presence of a putative novel
      melanoma susceptibility locus in the Swedish population, a finding that needs to
      be replicated in an independent study on other individuals with familial
      melanoma. Sequencing of genes in the region may identify novel melanoma
      associated mutations. 

PMID- 24721442
TI  - Assisted reproductive technology (ART) treatment in women with schizophrenia or
      related psychotic disorder: a national cohort study.
AB  - OBJECTIVES: To determine the prevalence rate of women with a diagnosis of
      schizophrenia or related psychotic disorder in assisted reproductive technology
      (ART) treatment and to study these women's fertility treatment outcome in
      comparison to women with no psychotic disorders. STUDY DESIGN: We used a national
      register-based cohort of 42,915 Danish women in ART treatment from 1.1.1994 to
      30.9.2009. All women with a diagnosis of schizophrenia or related psychotic
      disorders before, during or after their ART treatment were identified by
      individual-level linkage of nationwide registers of ART treatment, psychiatric
      admission, birth and socio-demographic status. The comparison group (N=42,671)
      consisted of all women in the study cohort never diagnosed with psychotic
      disorders. Conventional descriptive methods were used for the statistical
      analyses. RESULTS: Two hundred and forty-four (0.6%) women in the study cohort
      received a diagnosis of psychotic disorder before (N=135-55.3%), during (N=7
      2.9%) or after (N=102-41.8%) ART treatment. The mean time from last diagnosis of
      psychotic disorder to their first ART treatment in the 135 women with a
      psychiatric diagnosis prior to their first ART treatment was 7.1 +/- 5.6 years
      (25-75% percentile: +/-2.8-10.4 years). The most frequent diagnoses were acute
      and transient psychotic disorder. Women with a diagnosis of schizophrenia or
      related psychotic disorder before their first ART treatment had a lower ART
      treatment success rate as significantly fewer women obtained a live birth (40.0%
      vs. 51.9%, P<0.01). However, we found no statistical differences in perinatal
      outcomes for the children born by women in the study population and comparison
      group. CONCLUSIONS: The prevalence of women with a psychotic diagnosis in
      fertility treatment is lower than the prevalence in the general population. Women
      with a psychotic disorder prior to ART treatment have a lower fertility treatment
      success rate compared to women without psychotic disorder. Women with a psychotic
      disorder achieving delivery show similar obstetric outcomes to women with no
      psychotic disorder.

PMID- 24721443
TI  - Patterns of retreatment by radiotherapy.
AB  - AIMS: To describe patterns of treatment for those who receive more than one
      episode of megavoltage radiotherapy (retreatment) by cancer type for better
      service planning and benchmarking. MATERIALS AND METHODS: Institutional databases
      of all patients who received their first megavoltage radiotherapy for any type of
      cancer at the Liverpool and Macarthur Cancer Therapy Centres (LM), New South
      Wales, Australia, Royal Brisbane and Women's Hospital (RBWH), Queensland,
      Australia and Radiotherapeutic Institution Friesland (RIF), Leeuwarden, the
      Netherlands, over the period 1991-2009 were examined. Radiotherapy retreatment
      was defined as any radiotherapy episode, to any body site, after an initial
      episode of radiotherapy, for the same cancer diagnosis. The total retreatment
      rate was defined as the number of retreatment episodes of radiotherapy divided by
      the number of cases in the cohort. RESULTS: In total, 62,270 patients (RBWH
      38581, LM 9654, RIF 14035) received 77,762 episodes of radiotherapy, giving a
      total retreatment rate of 0.25; 52,351 patients (84%) received only one episode
      of treatment and 9919 (16%) received two or more episodes of treatment. Overall
      retreatment rates for LM, RBWH and RIF were 0.24, 0.25 and 0.26, respectively.
      For the five most common cancer types treated, the median time between treatment
      episodes was longest for breast cancer (11.3 months), then head and neck cancer
      (9.7 months), colorectal cancer (7.2 months), prostate cancer (4.4 months) and
      lung cancer (4.1 months). Ninety-one per cent of all fractions were delivered in
      the first episode of treatment. CONCLUSIONS: The retreatment rate was very
      similar between the three facilities, suggesting agreement about the indications
      for retreatment.

PMID- 24721444
TI  - Chemoradiotherapy for squamous cell cancer of the anal canal: a systematic
      review.
AB  - Squamous cell cancer of the anal canal is a rare tumour for which there remains
      uncertainty regarding optimal therapy. A systematic review was conducted to
      summarise the evidence examining concurrent chemotherapy and radiotherapy or
      different chemotherapy regimens in combination with radiotherapy. MEDLINE, EMBASE
      and conference proceedings were searched for relevant randomised controlled
      trials. Outcomes of interest were colostomy rate, local failure, overall
      survival, disease-free survival, adverse effects and quality of life. Six
      randomised controlled trials were identified. Two trials reported lower colostomy
      and local failure rates for concurrent 5-fluorouracil (5-FU) plus mitomycin C
      (MMC) and radiotherapy compared with radiotherapy alone. The omission of MMC from
      this regimen resulted in higher colostomy and local failure rates and lower
      disease-free survival. Induction chemotherapy followed by concurrent 5-FU plus
      cisplatin and radiotherapy resulted in a higher colostomy rate than concurrent 5
      FU plus MMC and radiotherapy. Haematological toxicity rates were lower in
      patients who received radiotherapy with 5-FU alone or 5-FU plus cisplatin
      compared with 5-FU plus MMC. No benefit was seen for the addition of induction or
      maintenance chemotherapy to concurrent chemoradiotherapy. The available evidence
      continues to support the use of radiotherapy with concurrent 5-FU and MMC as
      standard treatment for cancer of the anal canal to decrease colostomy and local
      failure rates. 

PMID- 24721445
TI  - The expression and phylogenetics of the Inhibitor Cysteine Knot peptide OCLP1 in
      the honey bee Apis mellifera.
AB  - Small cysteine-rich peptides have diverse functions in insects including
      antimicrobial defense, phenoloxidase activity regulation, and toxic inhibition of
      ion channels of prey or predator. We combined bioinformatics and measurements of
      transcript abundance to start characterizing AmOCLP1, a recently discovered
      Inhibitor Cysteine Knot peptide in the honey bee Apis mellifera. We found that
      the genomes of ants, bees, and the wasp Nasonia vitripennis encode orthologous
      sequences indicating that OCLP1 is a conserved peptide and not unique to the
      honey bee. Search of available EST libraries and quantitative real time PCR
      analyses indicate that the transcript of AmOCLP1 is ubiquitous with expression in
      life stages ranging from embryos to adults and in all tested tissues. In worker
      honey bees AmOCLP1 expression was not associated with age or task and did not
      show clear enrichment in any of the tested tissues. There was however a
      consistent trend toward higher transcript levels in the abdomen of foragers
      relative to levels in the head or thorax, and compared to levels in the abdomen
      of younger worker bees. By contrast, in drones AmOCLP1 transcript levels appeared
      higher in the head relative to the abdomen. Finer analyses of the head and
      abdomen indicated that the AmOCLP1 transcript is not enriched in the stinger and
      the associated venom sac or in cephalic exocrine glands. The evolutionary
      conservation in the Hymenoptera, the ubiquitous expression, and the lack of
      enrichment in the venom gland, stinger, exocrine glands, and the brain are not
      consistent with the hypotheses that OCLP1 is a secreted honeybee toxin or an
      endotoxin acting in the central nervous system. Rather we hypothesize that OCLP1
      is a conserved antimicrobial or phenoloxidase inhibitor peptide. 

PMID- 24721446
TI  - The multiple truths about crystal meth among young people entrenched in an urban
      drug scene: a longitudinal ethnographic investigation.
AB  - Transitions into more harmful forms of illicit drug use among youth have been
      identified as important foci for research and intervention. In settings around
      the world, the transition to crystal methamphetamine (meth) use among youth is
      considered a particularly dangerous and growing problem. Epidemiological evidence
      suggests that, particularly among young, street-involved populations, meth use is
      associated with numerous sex- and drug-related "risks behaviors" and negative
      health outcomes. Relatively few studies, however, have documented how youth
      themselves understand, experience and script meth use over time. From 2008 to
      2012, we conducted over 100 in-depth interviews with 75 street-entrenched youth
      in Vancouver, Canada, as well as ongoing ethnographic fieldwork, in order to
      examine youth's understandings and experiences of meth use in the context of an
      urban drug scene. Our findings revealed positive understandings and experiences
      of meth in relation to other forms of drug addiction and unaddressed mental
      health issues. Youth were simultaneously aware of the numerous health-related
      harms and social costs associated with heavy meth use. Over time, positive
      understandings of meth may become entirely contradictory to a lived reality in
      which escalating meth use is a factor in further marginalizing youth, although
      this may not lead to cessation of use. Recognition of these multiple truths about
      meth, and the social structural contexts that shape the scripting of meth use
      among youth in particular settings, may help us to move beyond moralizing debates
      about how to best educate youth on the "risks" associated with meth, and towards
      interventions that are congruent with youth's lived experiences and needs across
      the lifecourse. 

PMID- 24721447
TI  - Hidden harms: women's narratives of intimate partner violence in a microbicide
      trial, South Africa.
AB  - In a context of high rates of intimate partner violence (IPV), trials of female
      controlled technologies for HIV prevention such as microbicides may increase the
      possibility of social harms. Seeking to explore the relationship between IPV and
      microbicide use further, this paper documents women's narratives of participating
      in the Microbicide Development Program (MDP) trial in Johannesburg, South Africa,
      and experiences of partner violence and conflict. A social science sub-study,
      nested within the trial, was conducted between September 2005 and August 2009,
      and 401 serial in-depth-interviews were undertaken with 150 women. Using coded
      interview transcripts, we describe the distribution of IPV and the possible
      association thereof with microbicide gel use and trial participation. More than a
      third of these 150 women reported IPV, of which half the cases were related to
      involvement in the trial. In their narratives, those women reporting IPV cast
      their partners as authoritarian, controlling and suspicious and reported verbal
      abuse, abandonment, and in some cases, beatings. Shared experiences of everyday
      violence shaped women's feelings of unease about revealing their participation in
      the trial to intimate partners and attempted concealment further contributed to
      strains and conflict within relationships. Our findings point to the role of
      social scientific enquiry in identifying the less obvious, hidden negative
      impacts of participation in a clinical trial therefore exposing limitations in
      the biomedical construction of 'social harms', as well as the implications
      thereof for potential future use outside the clinical trial setting. 

PMID- 24721448
TI  - Synthetic antibody technologies.
AB  - Synthetic antibody technologies enable the rapid production of affinity reagents
      through in vitro selections. The production of synthetic antibodies relies on
      sophisticated design strategies to produce combinatorial diversity libraries that
      encode antibody populations optimized for molecular recognition. The technology
      takes advantage of display technologies that enable amplification, selection and
      manipulation of antibodies in vitro. The rapid yet highly controlled nature of
      these methods has opened new avenues in basic and clinical research. Here we
      review recent advances in structural biology facilitated by synthetic antibodies,
      as well as advances in library designs and selection methods. 

PMID- 24721450
TI  - Co-translational mechanisms of protein maturation.
AB  - Protein biogenesis integrates multiple finely regulated mechanisms, ensuring
      nascent polypeptide chains are correctly enzymatically processed, targeted to
      membranes and folded to native structure. Recent studies show that the cellular
      translation machinery serves as hub that coordinates the maturation events in
      space and time at various levels. The ribosome itself serves as docking site for
      a multitude of nascent chain-interacting factors. The movement of ribosomes along
      open reading frames is non-uniformous and includes pausing sites, which
      facilitates nascent chain folding and perhaps factor engagement. Here we
      summarize current knowledge and discuss emerging concepts underlying the critical
      interplay between translation and protein maturation in E. coli. 

PMID- 24721449
TI  - Template-based structure modeling of protein-protein interactions.
AB  - The structure of protein-protein complexes can be constructed by using the known
      structure of other protein complexes as a template. The complex structure
      templates are generally detected either by homology-based sequence alignments or,
      given the structure of monomer components, by structure-based comparisons.
      Critical improvements have been made in recent years by utilizing interface
      recognition and by recombining monomer and complex template libraries.
      Encouraging progress has also been witnessed in genome-wide applications of
      template-based modeling, with modeling accuracy comparable to high-throughput
      experimental data. Nevertheless, bottlenecks exist due to the incompleteness of
      the protein-protein complex structure library and the lack of methods for distant
      homologous template identification and full-length complex structure refinement. 

PMID- 24721451
TI  - Studying post-translational modifications with protein interaction networks.
AB  - At least 46 interactome studies, broad at proteome scale or biologically more
      focused, have together mapped about 75,000 human protein-protein interactions
      (PPIs). Many of the studies addressed local interactome data paucity analyzing
      specific homeostatic and regulatory systems, with recent focus demonstrating the
      involvement of post-translational protein modification (PTM) enzyme families in a
      wide range of cellular functions. These datasets provided insight into binding
      mechanisms, the dynamic modularity of complexes or delineated combinatorial
      enzymatic cascades. Furthermore, the combined study of PPI and PTM dynamics has
      begun to reveal conditional rewiring of molecular networks through PTM-mediated
      recognition events. Taken together these studies highlight the utility of local
      and global interaction networks to functionally prioritize the many changing PTMs
      mapped in human cells. 

PMID- 24721452
TI  - Structure determination of protein-protein complexes with long-range anisotropic
      paramagnetic NMR restraints.
AB  - Paramagnetic NMR spectroscopy has evolved rapidly in the last decade, and has
      shown to be a very useful tool for solving structures of protein-protein
      complexes. A major breakthrough has been the development of paramagnetic metal
      binding tags that can be attached specifically to the protein. These tags have
      greatly facilitated the use of anisotropic paramagnetic restraints such as
      pseudocontact shifts and residual dipolar couplings arising from paramagnetic
      self-alignment. Such restraints are particularly useful for the study of large
      protein complexes. This review focuses on the recent developments in structural
      characterization of protein-protein complexes using anisotropic paramagnetic NMR
      restraints. 

PMID- 24721453
TI  - Spectroscopic techniques for monitoring protein interactions in living cells.
AB  - Quantitative protein interaction analysis in living cells remains highly
      challenging as concentrations of interactions partners are difficult to quantify
      and to temporally modulate. In this review, the fundamental concepts for
      monitoring protein interactions in cells are discussed. Next to already well
      established resonance energy transfer-based techniques, recent developments of
      approaches based on single molecule fluctuation and localization are presented.
      Moreover, the application of surface micropatterning and functionalized
      nanoparticles for solid phase type of protein interaction analysis in living
      cells are introduced. The complementary capabilities and limitations of these
      techniques and future directions based technological developments are discussed. 

PMID- 24721454
TI  - Residue specific contributions to stability and activity inferred from saturation
      mutagenesis and deep sequencing.
AB  - Multiple methods currently exist for rapid construction and screening of single
      site saturation mutagenesis (SSM) libraries in which every codon or nucleotide in
      a DNA fragment is individually randomized. Nucleotide sequences of each library
      member before and after screening or selection can be obtained through deep
      sequencing. The relative enrichment of each mutant at each position provides
      information on its contribution to protein activity or ligand-binding under the
      conditions of the screen. Such saturation scans have been applied to diverse
      proteins to delineate hot-spot residues, stability determinants, and for
      comprehensive fitness estimates. The data have been used to design proteins with
      enhanced stability, activity and altered specificity relative to wild-type, to
      test computational predictions of binding affinity, and for protein model
      discrimination. Future improvements in deep sequencing read lengths and accuracy
      should allow comprehensive studies of epistatic effects, of combinational
      variation at multiple sites, and identification of spatially proximate residues. 

PMID- 24721455
TI  - Increasing occurrences and functional roles for high energy purine-pyrimidine
      base-pairs in nucleic acids.
AB  - There are a growing number of studies reporting the observation of purine
      pyrimidine base-pairs that are seldom observed in unmodified nucleic acids
      because they entail the loss of energetically favorable interactions or require
      energetically costly base ionization or tautomerization. These high energy purine
      pyrimidine base-pairs include G*C(+) and A*T Hoogsteen base-pairs, which entail
      ~180 degrees  rotation of the purine base in a Watson-Crick base-pair,
      protonation of cytosine N3, and constriction of the C1'-C1' distance by ~2.5A.
      Other high energy pure-pyrimidine base-pairs include G*T, G*U, and A*C mispairs
      that adopt Watson-Crick like geometry through either base ionization or
      tautomerization. Although difficult to detect and characterize using biophysical
      methods, high energy purine-pyrimidine base-pairs appear to be more common than
      once thought. They further expand the structural and functional diversity of
      canonical and non-canonical nucleic acid base-pairs. 

PMID- 24721456
TI  - A comprehensive electrocardiographic, molecular, and echocardiographic study of
      Brugada syndrome: validation of the 2013 diagnostic criteria.
AB  - BACKGROUND: The debate on the diagnostic value of high intercostal spaces (ICSs)
      and of the number of diagnostic leads in Brugada syndrome (BrS) has been settled
      by a recent expert consensus statement. OBJECTIVE: To test the validity, and the
      underlying anatomy, of the new electrocardiographic (ECG) diagnostic criteria
      using echocardiographic, molecular, and clinical evidence in 1 clinical study
      population with BrS. METHODS: We analyzed 114 patients with BrS and with a
      spontaneous or drug-induced type 1 ECG pattern recorded in 1 or more right
      precordial leads in fourth, third, and second ICSs. The right ventricular outflow
      tract (RVOT) was localized by using echocardiography. All probands were screened
      on the SCN5A gene. RESULTS: The percentage of mutation carriers (MCs) and the
      event rate were similar regardless of the diagnostic ICS (fourth vs high ICSs:
      MCs 23% vs 19%; event rate 22% vs 28%) and the number of diagnostic leads (1 vs
      >=2: MCs 20% vs 22%; event rate 22% vs 27%). The concordance between RVOT
      anatomical location and the diagnostic ICSs was 86%. The percentage of the
      diagnostic ECG pattern recorded was significantly increased by the exploration of
      the ICSs showing RVOT by echocardiography (echocardiography-guided approach vs
      conventional approach 100% vs 43%; P < .001). CONCLUSION: The high ICSs are not
      inferior to the standard fourth ICS for the ECG diagnosis of BrS, and the
      interindividual variability depends on the anatomical location of the RVOT as
      assessed by using echocardiography. This approach significantly increases
      diagnostic sensitivity without decreasing specificity and fully supports the
      recently published new diagnostic criteria.

PMID- 24721457
TI  - Fatigue behaviour of Nitinol peripheral stents: the role of plaque shape studied
      with computational structural analyses.
AB  - Fatigue resistance of Nitinol stents implanted into femoro-popliteal arteries is
      a critical issue for the particular biomechanical environment of this district.
      Hip and knee joint movements due to the cyclic daily activity expose the
      superficial femoral artery (SFA), and therefore the implanted stents, to quite
      large and cyclic deformations influencing stent fatigue resistance. Objective of
      this work is to provide a tool based on finite element analysis able to evaluate
      the biomechanical effect of SFA on stent fatigue resistance. Computer simulations
      of the treatment of stenotic vessel by angioplasty and stenting and of the
      subsequent in vivo loading conditions (axial compression and bending) were
      carried out. Three different stenotic vessel models were defined, by keeping a
      constant stenosis rate and changing the plaque sharpness and number of stenoses.
      The fatigue behaviour was analysed comparing the amplitude and mean value
      distribution of the first principal strain in the whole stent for the different
      simulated conditions. Results showed that the maximum mean strain is similar in
      all the models, while the alternating strain is related to both plaque shape and
      loading conditions. In conclusion, this study confirms the requisite of
      replicating in vivo loading conditions. It also reveals the importance of taking
      into account the thickness variation of the vessel in the stenotic zone in the
      assessment of the stent fatigue resistance. 

PMID- 24721458
TI  - Transfer function analysis for the assessment of cerebral autoregulation using
      spontaneous oscillations in blood pressure and cerebral blood flow.
AB  - Cerebral autoregulation (CA) is a key mechanism to protect the brain against
      excessive fluctuations in blood pressure (BP) and maintain cerebral blood flow.
      Analyzing the relationship between spontaneous BP and cerebral blood flow
      velocity (CBFV) using transfer function analysis is a widely used technique to
      quantify CA in a non-invasive way. The objective of this review was to provide an
      overview of transfer function techniques used in the assessment of CA. 113
      publications were included. This literature showed that there is no gold standard
      for the execution and implementation of the transfer function. There is a high
      diversity in settings and criteria used for transfer function analysis. Notable
      is also the high number of studies which report little on the settings. This
      disparity makes it difficult to replicate or compare the results of the different
      studies and further hinders the opportunity to make a distinction between intact
      and impaired CA in different patient groups. More research on the effects of
      different implementation techniques on CA results and optimization of the
      transfer function analysis is urgently needed. Furthermore, international
      guidelines should be created to inform the minimal description of the applied
      technique and the interpretation of transfer function outcomes in scientific
      research. 

PMID- 24721459
TI  - Celecoxib exerts protective effects on extracellular matrix metabolism of
      mandibular condylar chondrocytes under excessive mechanical stress.
AB  - OBJECTIVE: Excessive mechanical stress is considered a major cause of
      temporomandibular joint osteoarthritis (TMJ-OA). High magnitude cyclic tensile
      strain (CTS) up-regulates pro-inflammatory cytokines and matrix
      metalloproteinases (MMPs) in chondrocytes, while selective cyclooxygenase (COX)-2
      inhibition has been shown to be beneficial to cytokine-induced cartilage damage.
      However, the effect of selective COX-2 inhibitors on mechanically stimulated
      chondrocytes remains unclear. This study evaluated the effect of celecoxib, a
      selective COX-2 inhibitor, on extracellular matrix (ECM) metabolism of mandibular
      condylar chondrocytes under CTS. METHODS: Porcine mandibular chondrocytes were
      subjected to CTS of 0.5 Hz, 10% elongation with celecoxib for 24 h. The gene
      expressions of COX-2, MMPs, aggrecanase (ADAMTS), type II collagen and aggrecan
      were examined by real-time PCR. Also, prostaglandin E2 (PGE2) concentrations were
      determined using enzyme immunoassay kit. The levels of MMP and transcription
      factor NF-kappaB were measured by western blot while MMP activity was determined
      by casein zymography. RESULTS: The presence of celecoxib normalized the release
      of PGE2 and diminished the CTS-induced COX-2, MMP-1, MMP-3, MMP-9 and ADAMTS-5
      gene expressions while recovered the downregulated type II collagen and aggrecan
      gene expressions. Concurrently, celecoxib showed inhibition of NF-kappaB and
      suppression of MMP production and activity. CONCLUSIONS: Celecoxib exerts
      protective effects on mandibular condylar chondrocytes under CTS stimulation by
      diminishing degradation and restoring synthesis of ECM.

PMID- 24721460
TI  - Comparison of measurement properties of the P4 pain scale and disease specific
      pain measures in patients with knee osteoarthritis.
AB  - OBJECTIVE: To compare measurement properties of the P4 pain scale, Western
      Ontario and McMaster Universities Arthritis Index pain subscale (WOMAC-pain), and
      Intermittent and Constant Osteoarthritis Pain (ICOAP) measure in patients with
      knee osteoarthritis (OA). DESIGN: A secondary analysis from a randomized
      controlled trial included participants (n = 156) with knee OA that were
      consulting with a surgeon regarding knee arthroplasty. They completed pain
      measures (P4, WOMAC-pain, ICOAP) and WOMAC-function subscale (WOMAC-function) at
      baseline and 2 weeks. Measurement properties assessed in various subgroups
      included floor/ceiling effects, test-retest reliability using intraclass
      correlation coefficients (ICC2,1), internal consistency using Cronbach's alpha,
      factorial structure of each pain measure combined with WOMAC-function using
      principal component analysis, and responsiveness using standardized response mean
      (SRM). RESULTS: P4 had low floor and ceiling effects (<1%). P4 test-retest
      reliability (ICC2,1 = 0.72), internal consistency (Chronbach's alpha = 0.91), and
      responsiveness (SRM = 0.56) were similar to the values for WOMAC-pain and ICOAP.
      Factorial structure of P4 and ICOAP were separate from WOMAC-function items.
      WOMAC-pain and WOMAC-function items loaded on similar factors. ICOAP-constant
      subscale had a large floor effect (33%). CONCLUSIONS: P4 should be used to
      measure pain in patients with knee OA. It had acceptable measurement properties
      which is comparable to more widely used pain measures. WOMAC-pain shared a
      factorial structure with WOMAC-function indicating these measures might be
      capturing the same construct, questioning its validity to measure pain separately
      from function. ICOAP had acceptable properties. More work should compare pain
      measures in less severely affected OA populations.

PMID- 24721461
TI  - Infection of human monocytes by Chlamydia pneumoniae and Chlamydia trachomatis:
      an in vitro comparative study.
AB  - BACKGROUND: An increasing number of studies suggest that chlamydiae can infect
      immune cells. The altered immune cell function could contribute to the
      progression of several chronic inflammatory diseases.The aim of this study was to
      comparatively evaluate Chlamydia pneumoniae (CP) and Chlamydia trachomatis (CT)
      interactions with in vitro infected human blood monocytes. RESULTS: Fresh
      isolated monocytes were infected with viable CP and CT elementary bodies and
      infectivity was evaluated by recultivating disrupted monocytes in permissive
      epithelial cells.The production of reactive oxygen and nitrogen species was
      studied in the presence of specific fluorescent probes. Moreover, TNF-alpha, INF
      alpha, INF-beta and INF-gamma gene expression was determined. CT clearance from
      monocytes was complete at any time points after infection, while CP was able to
      survive up to 48 hours after infection. When NADPH oxydase or nitric oxide
      synthase inhibitors were used, CT infectivity in monocytes was restored, even if
      at low level, and CT recovery's rate was comparable to CP one.CT-infected
      monocytes produced significantly higher levels of reactive species compared with
      CP-infected monocytes, at very early time points after infection. In the same
      meanwhile, TNF-alpha and INF-gamma gene expression was significantly increased in
      CT-infected monocytes. CONCLUSIONS: Our data confirm that CP, but not CT, is able
      to survive in infected monocytes up to 48 hours post-infection. The delay in
      reactive species and cytokines production by CP-infected monocytes seems to be
      crucial for CP survival.

PMID- 24721463
TI  - Better and faster: improvements and optimization for mammalian recombinant
      protein production.
AB  - Thanks to numerous technological advances, the production of recombinant proteins
      in mammalian cell lines has become an increasingly routine task that is no longer
      viewed as a heroic enterprise. While production in prokaryotic or lower
      eukaryotic systems may be more rapid and economical, the advantages of producing
      large amounts of protein that closely resembles the native form is often
      advantageous and may be essential for the realization of functionally active
      material for biological studies or biopharmaceuticals. The correct folding,
      processing and post-translational modifications conferred by expression in a
      mammalian cell is relevant to all classes of proteins, including cytoplasmic,
      secreted or integral membrane proteins. Therefore considerable efforts have
      focused on the development of growth media, cell lines, transformation methods
      and selection techniques that enable the production of grams of functional
      protein in weeks, rather than months. This review will focus on a plethora of
      methods that are broadly applicable to the high yield production of any class of
      protein (cytoplasmic, secreted or integral membrane) from mammalian cells. 

PMID- 24721462
TI  - Role of human pregnane X receptor in high fat diet-induced obesity in pre
      menopausal female mice.
AB  - Obesity is a complex metabolic disorder that is more prevalent among women. Until
      now, the only relevant rodent models of diet-induced obesity were via the use of
      ovariectomized ("postmenopausal") females. However, recent reports suggest that
      the xenobiotic nuclear receptor pregnane X receptor (PXR) may contribute to
      obesity. Therefore, we compared the roles of mouse and human PXRs in diet-induced
      obesity between wild type (WT) and PXR-humanized (hPXR) transgenic female mice
      fed either control or high-fat diets (HFD) for 16 weeks. HFD-fed hPXR mice gained
      weight more rapidly than controls, exhibited hyperinsulinemia, and impaired
      glucose tolerance. Fundamental differences were observed between control-fed hPXR
      and WT females: hPXR mice possessed reduced estrogen receptor alpha (ERalpha) but
      enhanced uncoupling protein 1 (UCP1) protein expression in white adipose tissue
      (WAT); increased protein expression of the hepatic cytochrome P450 3A11 (CYP3A11)
      and key gluconeogenic enzymes phosphoenolpyruvate carboxykinase and glucose 6
      phosphatase, and increased total cholesterol. Interestingly, HFD ingestion
      induced both UCP1 and glucokinase protein expression in WT mice, but inhibited
      these enzymes in hPXR females. Unlike WT mice, CYP3A11 protein, serum 17beta
      estradiol levels, and WAT ERalpha expression were unaffected by HFD in hPXR
      females. Together, these studies indicate that the hPXR gene promotes obesity and
      metabolic syndrome by dysregulating lipid and glucose homeostasis while
      inhibiting UCP1 expression. Furthermore, our studies indicate that the human PXR
      suppresses the protective role of estrogen in metabolic disorders. Finally, these
      data identify PXR-humanized mice as a promising in vivo research model for
      studying obesity and diabetes in women. 

PMID- 24721465
TI  - A female case of benign symmetric lipomatosis associated with alcoholism.

PMID- 24721464
TI  - Evaluation of multiple measures of antiretroviral adherence in the Eastern
      European country of Georgia.
AB  - INTRODUCTION: There is little information on adherence to antiretroviral therapy
      (ART) in the Eastern European region. This prospective study evaluated multiple
      measures of adherence and their association with viral suppression among HIV
      patients in Georgia. METHODS: A prospective cohort study enrolled 100 consecutive
      antiretroviral-naive adult (age >= 18 years) patients, who were followed for
      three months. Adherence was assessed by medication refill and three self-report
      measures (an AIDS Clinical Trial Group [ACTG] tool for four-day adherence, a
      visual analogue scale [VAS] and a rating task for 30-day adherence). The VAS
      represented a line anchored by 0 and 100% corresponding to the percentage of
      prescribed doses taken. The rating task asked patients to rate their ability to
      take all medications as prescribed, with responses categorized into six levels of
      adherence: very poor (0%), poor (20%), fair (40%), good (60%), very good (80%)
      and excellent (100%). Patients with adherence of >= 95% by medication refill,
      ACTG and VAS, and >= 80% by rating task, were defined as adherent. RESULTS: Of
      100 patients enrolled, eight had missing data and were excluded from analysis.
      Among the remaining 92 patients, the median age was 39 years, and 70% were men.
      Major modes of HIV acquisition were injection drug use (IDU; 47.3%) and
      heterosexual contact (44.1%). The proportions of adherent patients were as
      follows: 68% by medication refill, 90% by ACTG questionnaire, 38% by VAS and 42%
      by rating task. On average, four months after commencing ART, 52 (56.5%) patients
      had a viral load <400 copies/ml and 26 (28.3%) patients had a viral load <50
      copies/ml. Of 43 persons with a history of IDU, 22 (51.2%) reached a viral load
      of <400 copies/ml. In multivariate analysis, only refill adherence was a
      statistically significant predictor of viral suppression of <400 copies/ml: the
      risk ratio was 1.7 (95% CI: 1.1-2.8). Refill adherence, VAS and rating task were
      associated with viral suppression of <50 copies/ml. Non-IDUs were twice as likely
      to achieve viral load <50 copies/ml compared to IDUs. Refill adherence had the
      largest area under the receiver-operating characteristic curve for predicting
      viral suppression. CONCLUSIONS: Medication refill adherence was the strongest
      predictor of viral suppression. IDUs can achieve optimal virologic outcomes, but
      may require additional adherence support.

PMID- 24721467
TI  - A single misstep in cardiac development explains the co-occurrence of tetralogy
      of fallot and complete atrioventricular septal defect in Down syndrome.
AB  - Tetralogy of Fallot and a complete atrioventricular septal defect are thought to
      arise by distinct mechanisms, yet their co-occurrence is a recognized
      association. Analysis of the prevalence of co-occurrence in Down syndrome
      suggests a common developmental basis. Trisomy 21 may perturb cardiac progenitor
      cells before they enter the heart tube.

PMID- 24721466
TI  - Harsh parenting and fearfulness in toddlerhood interact to predict amplitudes of
      preschool error-related negativity.
AB  - Temperamentally fearful children are at increased risk for the development of
      anxiety problems relative to less-fearful children. This risk is even greater
      when early environments include high levels of harsh parenting behaviors.
      However, the mechanisms by which harsh parenting may impact fearful children's
      risk for anxiety problems are largely unknown. Recent neuroscience work has
      suggested that punishment is associated with exaggerated error-related negativity
      (ERN), an event-related potential linked to performance monitoring, even after
      the threat of punishment is removed. In the current study, we examined the
      possibility that harsh parenting interacts with fearfulness, impacting anxiety
      risk via neural processes of performance monitoring. We found that greater
      fearfulness and harsher parenting at 2 years of age predicted greater fearfulness
      and greater ERN amplitudes at age 4. Supporting the role of cognitive processes
      in this association, greater fearfulness and harsher parenting also predicted
      less efficient neural processing during preschool. This study provides initial
      evidence that performance monitoring may be a candidate process by which early
      parenting interacts with fearfulness to predict risk for anxiety problems. 

PMID- 24721468
TI  - Growth and developmental outcomes of infants with hirschsprung disease presenting
      in the neonatal period: a retrospective study.
AB  - OBJECTIVES: To describe the presentation and progress over the first year of life
      of neonates with Hirschsprung disease, to describe their physical and
      developmental outcomes at 12 months of age, and to compare the outcomes of
      infants with short- vs long-segment Hirschsprung disease. STUDY DESIGN: A
      retrospective study of neonates born with Hirschsprung disease in Western
      Australia between January 1, 2001, and December 31, 2010, to review their
      presentation, progress, growth, and development at 12 months of age. RESULTS:
      Fifty-four infants were identified (40 with short and 11 with long segment and 3
      with total colonic aganglionosis); 9 infants had a recognized syndrome and 1
      infant died, unrelated to Hirschsprung disease. A primary pull-through procedure
      was performed in 97% and 21% of neonates with short- and non-short-segment
      Hirschsprung disease, respectively; 17 (31%) infants developed anal stenosis
      requiring dilatations. Enterocolitis occurred in 14 (26%) infants. Griffiths
      Mental Development Scale scores (1 year) were available in 31 of 45 nonsyndromic
      survivors: mean general quotient (94.2, SD 8.89) was significantly less than the
      population mean (P = .007), but the number of infants with developmental delay
      was within the expected range. Physical growth, except length, appeared adequate
      in nonsyndromic infants. There were no significant differences in the outcomes of
      infants with short- vs non-short-segment Hirschsprung disease. CONCLUSIONS: At 1
      year of age, many infants with Hirschsprung disease have ongoing gastrointestinal
      problems. Their overall growth appears satisfactory, and most infants are
      developing normally; however, their mean general quotient appears shifted to the
      left. Longer-term studies will better define developmental outcomes.

PMID- 24721469
TI  - Families facing language barriers in healthcare: when will policy catch up with
      the demographics and evidence?

PMID- 24721470
TI  - Parental perceptions of family and pediatrician roles in childhood weight
      management.
AB  - OBJECTIVE: To characterize parental perceptions of the respective roles of
      families and the pediatrician in childhood weight management. STUDY DESIGN:
      Structured in-person interviews (n = 69) were conducted with parents of children
      ages 3-12 years visiting a pediatric clinic. Interview topics included
      perceptions of weight and associated problems, child weight status and concerns,
      and the pediatrician's role in weight management. Interviews were coded
      qualitatively and analyzed thematically. RESULTS: Nine major themes were
      developed from the findings. Parents were clear about the health consequences of
      excess weight but were not clear about the concept of body mass index, often
      relying on visual cues or symptoms to identify excess weight. Parents relied on
      pediatricians to identify weight problems and suggest diet and exercise plans,
      but few recognized them as a link to additional weight-management resources.
      Parents were divided on the role of the pediatrician in managing child weight and
      were most interested in receiving tailored nutrition information. Parents
      preferred family behavioral change strategies over singling out an overweight
      child. Although parents did not always define their child as overweight, many
      parents of overweight children did express concerns about their child's weight.
      CONCLUSIONS: Parents believe that pediatricians have a central role in
      identifying childhood weight problems by completing screening tests such as body
      mass index assessments, interpreting the health implications, and communicating
      those implications to parents. Ensuring that parents understand the health
      implications of excess weight is critical given gaps in parental knowledge and
      confidence with healthy lifestyle changes as well as parental ambivalence toward
      child-directed interventions.

PMID- 24721471
TI  - Reply to Jacques Hubert and Richard M. Satava's letter to the editor re:
      Nicolomaria Buffi, Henk Van Der Poel, Giorgio Guazzoni, Alexander Mottrie, on
      behalf of the Junior European Association of Urology (EAU) Robotic Urology
      Section with the collaboration of the EAU Young Academic Urologists Robotic
      Section. Methods and priorities of robotic surgery training program. Eur Urol
      2014;65:1-2.

PMID- 24721472
TI  - Construction and analysis of a human hepatotoxicity database suitable for QSAR
      modeling using post-market safety data.
AB  - Drug-induced liver injury (DILI) is one of the most common drug-induced adverse
      events (AEs) leading to life-threatening conditions such as acute liver failure.
      It has also been recognized as the single most common cause of safety-related
      post-market withdrawals or warnings. Efforts to develop new predictive methods to
      assess the likelihood of a drug being a hepatotoxicant have been challenging due
      to the complexity and idiosyncrasy of clinical manifestations of DILI. The FDA
      adverse event reporting system (AERS) contains post-market data that depict the
      morbidity of AEs. Here, we developed a scalable approach to construct a
      hepatotoxicity database using post-market data for the purpose of quantitative
      structure-activity relationship (QSAR) modeling. A set of 2029 unique and
      modelable drug entities with 13,555 drug-AE combinations was extracted from the
      AERS database using 37 hepatotoxicity-related query preferred terms (PTs). In
      order to determine the optimal classification scheme to partition positive from
      negative drugs, a manually-curated DILI calibration set composed of 105 negatives
      and 177 positives was developed based on the published literature. The final
      classification scheme combines hepatotoxicity-related PT data with supporting
      information that optimize the predictive performance across the calibration set.
      Data for other toxicological endpoints related to liver injury such as liver
      enzyme abnormalities, cholestasis, and bile duct disorders, were also extracted
      and classified. Collectively, these datasets can be used to generate a battery of
      QSAR models that assess a drug's potential to cause DILI. 

PMID- 24721473
TI  - EWSR1 and ATF1 rearrangements in clear cell odontogenic carcinoma: presentation
      of a case.
AB  - Clear cell odontogenic carcinoma (CCOC) is a rare odontogenic tumor of the jaws
      that is more common in the mandible than maxilla and has a female preponderance
      with a peak incidence in the sixth decade. It is characterized by locally
      aggressive behavior and has the potential to metastasize. This tumor was recently
      reported to have a rearrangement of the Ewing sarcoma breakpoint region 1 gene
      (EWS RNA-binding protein 1, EWSR1) in 5 of 8 cases tested and of the activating
      transcription factor 1 gene (ATF1) in 1 case tested. We report a case of CCOC in
      the premolar area of the mandible in a 59-year-old woman. This case demonstrated
      the presence of both EWSR1 and ATF1 gene rearrangements by fluorescence in situ
      hybridization.

PMID- 24721474
TI  - Establishing the plane of symmetry for lumen formation and bilateral brain
      formation in the zebrafish neural rod.
AB  - The lumen of the zebrafish neural tube develops precisely at the midline of the
      solid neural rod primordium. This process depends on cell polarisation and cell
      rearrangements, both of which are manifest at the midline of the neural rod. The
      result of this cell polarisation and cell rearrangement is an epithelial tube
      that has overt mirror-symmetry, such that cell morphology and apicobasal
      polarisation are mirrored across the midline of the neural tube. This article
      discusses how this mirror-symmetry is established and proposes the hypothesis
      that positioning the cells' centrosomes to the midline of the neural rod is a key
      event in organising this process. 

PMID- 24721475
TI  - Tip cells: master regulators of tubulogenesis?
AB  - The normal development of an organ depends on the coordinated regulation of
      multiple cell activities. Focusing on tubulogenesis, we review the role of
      specialised cells or groups of cells that are selected from within tissue
      primordia and differentiate at the outgrowing tips or leading edge of developing
      tubules. Tip or leading cells develop distinctive patterns of gene expression
      that enable them to act both as sensors and transmitters of intercellular
      signalling. This enables them to explore the environment, respond to both tissue
      intrinsic signals and extrinsic cues from surrounding tissues and to regulate the
      behaviour of their neighbours, including the setting of cell fate, patterning
      cell division, inducing polarity and promoting cell movement and cell
      rearrangements by neighbour exchange. Tip cells are also able to transmit
      mechanical tension to promote tissue remodelling and, by interacting with the
      extracellular matrix, they can dictate migratory pathways and organ shape. Where
      separate tubular structures fuse to form networks, as in the airways of insects
      or the vascular system of vertebrates, specialised fusion tip cells act to
      interconnect disparate elements of the developing network. Finally, we consider
      their importance in the maturation of mature physiological function and in the
      development of disease. 

PMID- 24721476
TI  - Stochastic modeling of a serial killer.
AB  - We analyze the time pattern of the activity of a serial killer, who during 12
      years had murdered 53 people. The plot of the cumulative number of murders as a
      function of time is of "Devil's staircase" type. The distribution of the
      intervals between murders (step length) follows a power law with the exponent of
      1.4. We propose a model according to which the serial killer commits murders when
      neuronal excitation in his brain exceeds certain threshold. We model this neural
      activity as a branching process, which in turn is approximated by a random walk.
      As the distribution of the random walk return times is a power law with the
      exponent 1.5, the distribution of the inter-murder intervals is thus explained.
      We illustrate analytical results by numerical simulation. Time pattern activity
      data from two other serial killers further substantiate our analysis.

PMID- 24721477
TI  - A stochastic model of neurogenesis controlled by a single factor.
AB  - The researches on cortical neurogenesis reveal that asymmetric division plays a
      key role in controlling the balance between the self-renewal of stem cells and
      the beginning of the neural differentiation. In such a process a neural stem cell
      divides by mitosis, originating a postmitotic neuron and other pluripotent stem
      cell available for subsequent differentiation events. In addition, studies of
      cell lineage trees of cultured neural progenitors reveal tree shapes and subtrees
      recurrent, consistent with a stochastic model of division
      symmetrical/asymmetrical. These considerations have led us to develop a
      stochastic model of neurogenesis in order to explore the possibility that this is
      controlled primarily by a single factor (i.e. the concentration of mNumb in the
      cell). We contrast the predictions of our model with experimental data and
      compare it with other models of neurogenesis. 

PMID- 24721478
TI  - Pregnancy sickness and parent-offspring conflict over thyroid function.
AB  - Pregnancy sickness is widespread in human mothers but its etiology, somewhat
      surprisingly, remains unclear. Human chorionic gonadotropin (hCG) has long been
      considered a prime hormonal suspect, but the correlation between pregnancy
      sickness and hCG levels is imperfect resulting in uncertainty about its causal
      role. As others have noted part of this uncertainty likely stems from the
      structural and functional diversity of hCG. One enigmatic role of hCG is its
      action as a thyroid stimulator during early gestation. Native hCG is weakly
      thyrotropic but is produced in prodigious quantities and suppresses the
      production of thyroid stimulating hormone (TSH) but not curiously when TSH levels
      are in the higher deciles. Higher levels of hCG induce higher maternal production
      of thyroxine (T4). hCG thus appears to augment and sometimes even supplant TSH in
      the regulation of thyroid hormone in early gestation. This has lead to the
      suggestion that hCG serves as a backup system, albeit incomplete, for the
      production of essential thyroid hormone during pregnancy. Another interpretation,
      however, is that hCG, produced by the embryo, serves as a second control circuit
      for the thyroid during pregnancy. If so, it serves embryonic interests that are
      at odds with maternal interests (maternal-embryo conflict) under conditions of
      iodine deficiency. Iodine is an essential micronutrient for neurodevelopment and
      thyroid function, and has been in short supply for most humans over most of our
      evolutionary history. Iodine deficiency during gestation has severe impacts on
      embryo neuromotor development, but also induces thyroid disease in mothers,
      impairing her future reproductive prospects. Under this view, embryos use hCG to
      push mothers to release more thyroid hormone. hCG, however, is produced outside
      the normal maternal thyroid control circuit and thus is not subject to a normal
      negative feedback. hCG also serves multiple functions simultaneously therefore
      its production is likely not fine-tuned for thyroid function per se. hCG levels
      may remain high even when thyroid hormone production is more than sufficient to
      meet the needs of mother and embryo. Instead, the system appears to be regulated
      at the back end by clearing surplus hormone using placental Type II (D2) and Type
      III (D3) deiodinases. As maternal thyroid hormone levels rise, placental D3 is
      upregulated, shunting more T4 and T3 into a deactivating pathway. The metabolites
      that result, particularly the inert metabolite of T4, reverse T3, are correlates
      of surplus thyroid hormone production and thus are strong candidates for the
      proximate triggers of pregnancy sickness. Nausea and vomiting of early pregnancy
      thus arises as a by-product of an antagonistic pleiotropy between mother and
      embryo over the allocation of iodine: when dietary iodine is scarce, a benefit
      accrues to the embryo at a cost to mother; when iodine is plentiful, pregnancy
      sickness ranging from frequently mild to occasionally severe, is a sequelae of
      undiminished embryonic demands. If pregnancy sickness serves as a marker of
      thyroid function, an absence of first trimester nausea and vomiting sickness may
      indicate a higher priority for testing of thyroid function to avert the inimical
      effects of hypothyroidism during gestation. 

PMID- 24721479
TI  - Indirect reciprocity in three types of social dilemmas.
AB  - Indirect reciprocity is a key mechanism for the evolution of human cooperation.
      Previous studies explored indirect reciprocity in the so-called donation game, a
      special class of Prisoner's Dilemma (PD) with unilateral decision making. A more
      general class of social dilemmas includes Snowdrift (SG), Stag Hunt (SH), and PD
      games, where two players perform actions simultaneously. In these simultaneous
      move games, moral assessments need to be more complex; for example, how should we
      evaluate defection against an ill-reputed, but now cooperative, player? We
      examined indirect reciprocity in the three social dilemmas and identified twelve
      successful social norms for moral assessments. These successful norms have
      different principles in different dilemmas for suppressing cheaters. To suppress
      defectors, any defection against good players is prohibited in SG and PD, whereas
      defection against good players may be allowed in SH. To suppress unconditional
      cooperators, who help anyone and thereby indirectly contribute to jeopardizing
      indirect reciprocity, we found two mechanisms: indiscrimination between actions
      toward bad players (feasible in SG and PD) or punishment for cooperation with bad
      players (effective in any social dilemma). Moreover, we discovered that social
      norms that unfairly favor reciprocators enhance robustness of cooperation in SH,
      whereby reciprocators never lose their good reputation.

PMID- 24721481
TI  - Targeting tobacco in a community-based addiction recovery cohort: results from a
      computerized, brief, randomized intervention trial.
AB  - INTRODUCTION: Nearly 80% of substance dependent individuals also use tobacco, and
      smoking cessation efforts during treatment for other substance use is associated
      with similar or even improved outcomes. However, smoking cessation is not
      routinely addressed during treatment for substance use disorders. The present
      study tested a computerized brief motivational intervention (C-BMI) for smoking
      cessation in an understudied population: a cohort recruited from a recovery
      community organization (RCO) center. METHODS: Following baseline assessment,
      participants were randomly assigned to either a 30-minute C-BMI plus access to
      free nicotine replacement therapy (NRT), or an information-only control group
      plus NRT access. RESULTS: Reductions in CO were observed for both groups. Quit
      rates in the C-BMI group (5%-7%, vs. 0% for the control group) approximated those
      observed elsewhere for physician advice and minimal counseling. Participants in
      the C-BMI group were also more likely to express a desire to quit. CONCLUSIONS:
      Computer-delivered smoking cessation interventions within RCOs appear feasible.
      These organizations treat a wide variety of individuals, and C-BMIs for smoking
      in this context have the potential to reduce smoking-related morbidity and
      mortality.

PMID- 24721480
TI  - Vulnerable blood in high risk vascular patients: study design and methods.
AB  - BACKGROUND: Basic research suggests that rapid increases in circulating
      inflammatory and hemostatic blood markers may trigger or indicate impending
      plaque rupture and coronary thrombosis, resulting in acute ischemic heart disease
      (IHD) events. However, these associations are not established in humans. METHODS
      AND RESULTS: The Biomarker Risk Assessment in Vulnerable Outpatients (BRAVO)
      Study will determine whether levels of inflammatory and hemostatic biomarkers
      rapidly increase during the weeks prior to an acute IHD event in people with
      lower extremity peripheral artery disease (PAD). The BRAVO Study will determine
      whether biomarker levels measured immediately prior to an IHD event are higher
      than levels not preceding an IHD event; whether participants who experience an
      IHD event (cases) have higher biomarker levels immediately prior to the event and
      higher biomarker levels at each time point leading up to the IHD event than
      participants without an IHD event (controls); and whether case participants have
      greater increases in biomarkers during the months leading up to the event than
      controls. BRAVO enrolled 595 patients with PAD, a population at high risk for
      acute IHD events. After a baseline visit, participants returned every two months
      for blood collection, underwent an electrocardiogram to identify new silent
      myocardial infarctions, and were queried about new hospitalizations since their
      prior study visit. Mortality data were also collected. Participants were followed
      prospectively for up to three years. CONCLUSIONS: BRAVO results will provide
      important information about the pathophysiology of IHD events and may lead to
      improved therapies for preventing IHD events in high-risk patients.

PMID- 24721482
TI  - Assessment of Life's Simple 7 in the primary care setting: the Stroke Prevention
      in Healthcare Delivery EnviRonmEnts (SPHERE) study.
AB  - BACKGROUND: Adverse health behaviors and factors predict increased coronary heart
      disease and stroke risk, and effective use of health information technology (HIT)
      to automate assessment of and intervention on these factors is needed. A
      comprehensive, automated cardiovascular health (CVH) assessment deployed in the
      primary care setting offers the potential to enhance prevention, facilitate
      patient-provider communication, and ultimately reduce cardiovascular (CV) disease
      risk. We describe the methods for a study to develop and test an automated CVH
      application for stroke prevention in older women. METHODS AND RESULTS: The
      eligible study population for the Stroke Prevention in Healthcare Delivery
      EnviRonmEnts (SPHERE) study is approximately 1600 female patients aged 65 years
      and older and their primary care providers at The Ohio State University Wexner
      Medical Center. We will use an intervention design that will allow for a run-in
      period, comparison group data collection, a provider education period, and
      implementation of a best practice alert to prompt provider-patient interactions
      regarding CVH. Our primary outcome is a CVH score, comprising Life's Simple 7:
      smoking status, body mass index, blood pressure, cholesterol, fasting glucose,
      physical activity, and diet. The SPHERE application will generate visualizations
      of the CVH score within the electronic health record (EHR) during the patient
      provider encounter. A key outcome of the study will be change in mean CVH score
      pre- and post-intervention. CONCLUSIONS: The SPHERE application leverages the EHR
      and may improve health outcomes through HIT designed to empower clinicians to
      discuss CVH with their patients and enhance primary prevention efforts.

PMID- 24721483
TI  - Study of Tomography Of Nephrolithiasis Evaluation (STONE): methodology, approach
      and rationale.
AB  - BACKGROUND: Urolithiasis (kidney stones) is a common reason for Emergency
      Department (ED) visits, accounting for nearly 1% of all visits in the United
      States. Computed tomography (CT) has become the most common imaging test for
      these patients but there are few comparative effectiveness data to support its
      use in comparison to ultrasound. This paper describes the rationale and methods
      of STONE (Study of Tomography Of Nephrolithiasis Evaluation), a pragmatic
      randomized comparative effectiveness trial comparing different imaging strategies
      for patients with suspected urolithiasis. METHODS: STONE is a multi-center, non
      blinded pragmatic randomized comparative effectiveness trial of patients between
      ages 18 and 75 with suspected nephrolithiasis seen in an ED setting. Patients
      were randomized to one of three initial imaging examinations: point-of-care
      ultrasound, ultrasound performed by a radiologist or CT. Participants then
      received diagnosis and treatment per usual care. The primary aim is to compare
      the rate of severe SAEs (Serious Adverse Events) between the three arms. In
      addition, a broad range of secondary outcomes was assessed at baseline and
      regularly for six months post-baseline using phone, email and mail
      questionnaires. RESULTS: Excluding 17 patients who withdrew after randomization,
      a total of 2759 patients were randomized and completed a baseline questionnaire
      (n=908, 893 and 958 in the point-of-care ultrasound, radiology ultrasound and
      radiology CT arms, respectively). Follow-up is complete, and full or partial
      outcomes were assessed on over 90% of participants. CONCLUSIONS: The detailed
      methodology of STONE will provide a roadmap for comparative effectiveness studies
      of diagnostic imaging conducted in an ED setting.

PMID- 24721484
TI  - Left ventricular myocardial performance index predicts poor outcome during COPD
      exacerbation.

PMID- 24721485
TI  - CCR5del32 polymorphism is a protective factor in non-ischemic cardiomyopathy.

PMID- 24721486
TI  - Chronic right ventricular apical pacing: adverse effects and current therapeutic
      strategies to minimize them.
AB  - The permanent cardiac pacemaker is the only effective therapy for patients with
      symptomatic bradycardia and hundreds of millions are implanted worldwide every
      year. Despite its undisputed clinical benefits, the last two decades have drawn
      much attention to the negative effects associated with long-term pacing of the
      right ventricle (RV). Experimental and clinical studies have shown that RV pacing
      produces ventricular dyssynchrony, similar to that of left bundle branch block,
      with consequent detrimental effects on cardiac structure and function, with
      adverse clinical outcomes such as atrial fibrillation, heart failure and death.
      Although clinical evidence largely comes from subanalyses of pacemaker and
      implantable cardiac defibrillator studies, there is strong evidence that patients
      with reduced left ventricular function are at high risk of suffering from the
      detrimental effects of long-term RV pacing. Biventricular pacing in cardiac
      resynchronization therapy devices can prevent ventricular dyssynchrony and has
      emerged as an attractive option in this patient group with promising results and
      more clinical studies underway. Moreover, there is evidence that specific
      pacemaker algorithms that minimize RV pacing can reduce the negative effects of
      RV stimulation on cardiac function and may also prevent clinical deterioration.
      The extent of the long-term clinical effects of RV pacing in patients with normal
      ventricular function and how to prevent this are less clear and subject to future
      investigation. 

PMID- 24721487
TI  - Plasma osteoprotegerin levels are determined by primary cardiovascular events in
      late middle-aged but not in young elderly male subjects.

PMID- 24721488
TI  - Characteristics of smokers who have never tried to quit: evidence from the
      British Opinions and Lifestyle Survey.
AB  - BACKGROUND: An understanding of the characteristics of smokers who have never
      tried to quit may be useful to help identify and target these individuals and
      encourage them to attempt to give up smoking. Using national survey data we
      investigated variables associated with smokers reporting never having tried to
      quit. METHODS: Using data from the 2007 and 2009 UK Office for National
      Statistics Opinions and Lifestyle Survey we identified all self-reported current
      smokers aged 16+. The primary outcome was response to the question 'have you ever
      tried to quit smoking?' Univariable and multivariable logistic regression
      quantified the association between this outcome and several potential explanatory
      variables, including age, sex, socioeconomic status, health status, smoking
      behaviour, and knowledge of the dangers of smoking. RESULTS: Desire to quit was
      the most significant independent predictor of whether a smoker reported never
      having tried to quit. Smokers who reported that their health was good or very
      good were more likely to report never having tried to quit than those whose
      health was fair, bad or very bad (OR 1.59, 95% CI 1.05-2.41). Smokers who
      reported that no family members, friends or colleagues had been trying to get
      them to quit smoking in the last year were more likely to report never having
      tried to quit than those who reported that someone was trying to persuade them
      (OR 1.57, 95% CI 1.09-2.28). Smokers who hadn't received any cessation advice
      from a health professional in the last five years which they considered to be
      helpful were also more likely to report never having tried to quit. CONCLUSIONS:
      Smokers who do not want to quit, who are in good health, whose friends and family
      are not trying to get them to quit, and who do not report receiving helpful
      advice to quit from a health professional, are more likely to report never having
      tried to quit.

PMID- 24721489
TI  - Influence of data quality on computed Dutch hospital quality indicators: a case
      study in colorectal cancer surgery.
AB  - BACKGROUND: Our study aims to assess the influence of data quality on computed
      Dutch hospital quality indicators, and whether colorectal cancer surgery
      indicators can be computed reliably based on routinely recorded data from an
      electronic medical record (EMR). METHODS: Cross-sectional study in a department
      of gastrointestinal oncology in a university hospital, in which a set of 10
      indicators is computed (1) based on data abstracted manually for the national
      quality register Dutch Surgical Colorectal Audit (DSCA) as reference standard and
      (2) based on routinely collected data from an EMR. All 75 patients for whom data
      has been submitted to the DSCA for the reporting year 2011 and all 79 patients
      who underwent a resection of a primary colorectal carcinoma in 2011 according to
      structured data in the EMR were included. Comparison of results, investigating
      the causes for any differences based on data quality analysis. Main outcome
      measures are the computability of quality indicators, absolute percentages of
      indicator results, data quality in terms of availability in a structured format,
      completeness and correctness. RESULTS: All indicators were fully computable based
      on the DSCA dataset, but only three based on EMR data, two of which were
      percentages. For both percentages, the difference in proportions computed based
      on the two datasets was significant.All required data items were available in a
      structured format in the DSCA dataset. Their average completeness was 86%, while
      the average completeness of these items in the EMR was 50%. Their average
      correctness was 87%. CONCLUSIONS: Our study showed that data quality can
      significantly influence indicator results, and that our EMR data was not suitable
      to reliably compute quality indicators. EMRs should be designed in a way so that
      the data required for audits can be entered directly in a structured and coded
      format.

PMID- 24721490
TI  - Direct endoscopic jejunosotomy for the administration of levodopa-carbidopa
      intestinal gel in Parkinson's disease.

PMID- 24721491
TI  - Late-onset Huntington's disease: diagnostic and prognostic considerations.
AB  - OBJECTIVE: To address diagnostic and prognostic issues in patients with late
      onset Huntington's disease (HD). METHODS: We analyzed a cohort of 41 late-onset
      (>=60 years) HD patients and compared them to 39 late-onset patients referred for
      HD testing that were negative for the HD-expansion and to 290 usual-onset (20-59
      years) HD patients. Disease severity was assessed by the Total Functional
      Capacity Scale. RESULTS: Late-onset HD comprised 11.5% of our HD cohort. In
      total, 70.7% of late-onset HD patients had positive family history compared to
      15.4% of late-onset expansion-negative patients (p < 0.001). Clinical features at
      onset or presentation could not usefully distinguish between late-onset expansion
      positive and negative patients, excepting hemichorea, which was absent from the
      HD group (p = 0.024). Chorea was the first clinical feature in 53.7% and a
      presenting feature in 90.2% of late-onset HD. The mutation hit rate for late
      onset patients was 51.3%, lower than in usual-onset patients (p = 0.04).
      Frequencies of chorea, cognitive impairment and psychiatric manifestations at
      onset or presentation were not significantly different between late-onset and
      usual-onset HD patients. Gait unsteadiness however was more common at
      presentation in late-onset HD (p = 0.007). Late-onset HD patients reached a
      severe stage of illness on average 2.8 years earlier than usual-onset HD patients
      (p = 0.046). CONCLUSIONS: A positive family history suggestive of HD, although
      absent in a third of patients, remains a helpful clue in diagnosing late-onset
      HD. Prognosis of late-onset HD in terms of Total Functional Capacity appears no
      better and shows a trend of being somewhat less favorable compared to usual-onset
      HD.

PMID- 24721492
TI  - Hydrogen production from banyan leaves using an atmospheric-pressure microwave
      plasma reactor.
AB  - Growth of the hydrogen market has motivated increased study of hydrogen
      production. Understanding how biomass is converted to hydrogen gas can help in
      evaluating opportunities for reducing the environmental impact of petroleum-based
      fuels. The microwave power used in the reaction is found to be proportional to
      the rate of production of hydrogen gas, mass of hydrogen gas produced per gram of
      banyan leaves consumed, and amount of hydrogen gas formed with respect to the H
      atom content of banyan leaves decomposed. Increase the microwave power levels
      results in an increase of H2 and decrease of CO2 concentrations in the gaseous
      products. This finding may possibly be ascribed to the water-gas shift reaction.
      These results will help to expand our knowledge concerning banyan leaves and
      hydrogen yield on the basis of microwave-assisted pyrolysis, which will improve
      the design of hydrogen production technologies. 

PMID- 24721493
TI  - Enhanced adsorption of perfluorooctane sulfonate and perfluorooctanoate by bamboo
      derived granular activated carbon.
AB  - A bamboo-derived granular activated carbon with large pores was successfully
      prepared by KOH activation, and used to remove perfluorooctane sulfonate (PFOS)
      and perfluorooctanoate (PFOA) from aqueous solution. The granular activated
      carbon prepared at the KOH/C mass ratio of 4 and activation temperature of 900
      degrees C had fast and high adsorption for PFOS and PFOA. Their adsorption
      equilibrium was achieved within 24h, which was attributed to their fast diffusion
      in the micron-sized pores of activated carbon. This granular activated carbon
      exhibited the maximum adsorbed amount of 2.32mmol/g for PFOS and 1.15mmol/g for
      PFOA at pH 5.0, much higher than other granular and powdered activated carbons
      reported. The activated carbon prepared under the severe activation condition
      contained many enlarged pores, favorable for the adsorption of PFOS and PFOA. In
      addition, the spent activated carbon was hardly regenerated in NaOH/NaCl
      solution, while the regeneration efficiency was significantly enhanced in hot
      water and methanol/ethanol solution, indicating that hydrophobic interaction was
      mainly responsible for the adsorption. The regeneration percent was up to 98%
      using 50% ethanol solution at 45 degrees C. 

PMID- 24721494
TI  - The effect of warfare on the secular trends in sex ratios at birth in Israel,
      Egypt, and Kuwait over the past 60 years.

PMID- 24721495
TI  - Aminophylline increases respiratory muscle activity during hypercapnia in humans.
AB  - BACKGROUND: Theophylline is an old drug traditionally used as a bronchodilator,
      although it was recently shown to possess anti-inflammatory properties, enhance
      the actions of corticosteroid actions, and stimulate the respiratory neuronal
      network. Theophylline has been recognized as an important drug for not only
      asthma but also corticosteroid-insensitive chronic obstructive pulmonary disease
      (COPD). To clarify the role of theophylline in hypercapnic ventilatory responses
      in humans, we analyzed the effects of aminophylline administered at the usual
      clinical therapeutic doses on ventilation and augmentation of respiratory muscle
      contractility in room air and under 3 conditions of hypercapnia. STUDY DESIGN: We
      performed electromyography (EMG) of the parasternal intercostal muscle (PARA) and
      transversus abdominis muscle (TA) in 7 healthy subjects and recorded both
      ventilatory parameters and EMG data in room air and under 3 conditions of
      hypercapnia before (control) and during aminophylline administration. RESULTS:
      Before aminophylline administration (control), hypercapnic stimulation elicited
      ventilatory augmentation in a hypercapnia intensity-dependent manner. Ventilatory
      parameters (tidal volume, frequency of respiration, and minute ventilation)
      showed significant increases from lower PaCO2 levels during aminophylline
      administration when compared with the corresponding values before aminophylline
      administration. EMG activity of both PARA and TA increased significantly at each
      level of hypercapnia, and those augmentations were shown from lower PaCO2 levels
      during aminophylline administration. CONCLUSION: Aminophylline administered at
      the usual clinical therapeutic dose increases ventilation and EMG activity of
      both inspiratory and expiratory muscles during hypercapnia in healthy humans.

PMID- 24721496
TI  - Hepatitis C virus and microRNAs: miRed in a host of possibilities.
AB  - It is well-established that the host microRNA (miRNA) milieu has a significant
      influence on the etiology of disease. In the context of viruses, such as
      hepatitis C virus (HCV), microRNAs have been shown to influence viral life cycles
      both directly, through interactions with the viral genome, and indirectly,
      through regulation of critical virus-associated host pathways. Several miRNA
      profiling studies have demonstrated that HCV infection aberrantly regulates a
      significant number of human miRNA. However, the biological relevance of these
      modulations remains poorly understood. In this review, we summarize recent
      research that has shed light on the pro-viral and anti-viral roles of HCV-induced
      changes in human miRNA expression and their significance in the development of
      HCV related sequelae and response to therapy. 

PMID- 24721497
TI  - Hepatitis C virus and human miR-122: insights from the bench to the clinic.
AB  - MicroRNAs (miRNAs) are small non-coding RNAs that function as part of RNA-induced
      silencing complexes that repress the expression of target genes. Over the past
      few years, miRNAs have been found to mediate complex regulation of a wide variety
      of mammalian viral infections, including Hepatitis C virus (HCV) infection. Here,
      we focus on a highly abundant, liver-specific miRNA, miR-122. In a unique and
      unusual interaction, miR-122 binds to two sites in the 5' untranslated region
      (UTR) of the HCV genome and promotes viral RNA accumulation. We will discuss what
      has been learned about this important interaction to date, provide insights into
      how miR-122 is able to modulate HCV RNA accumulation, and how miR-122 might be
      exploited for antiviral intervention. 

PMID- 24721498
TI  - Retrofitting a crown to a sleep apnea device by using computer-aided design and
      computer-aided milling technology.
AB  - Retrofitting a new crown to an existing dental device is challenging. The
      continued evolution of computer-aided design and computer-aided manufacturing
      (CAD/CAM) significantly simplifies the process. This article demonstrates
      retrofitting a gold crown to an existing sleep apnea device. 

PMID- 24721499
TI  - The lamp die: an additional capacity of the alveolar model.

PMID- 24721500
TI  - Tooth wear: a systematic review of treatment options.
AB  - STATEMENT OF PROBLEM: Treatment of tooth wear is increasing. Because no evidence
      based guidelines are available, the clinician may have difficulties deciding
      which treatment option to choose to resolve complex situations. PURPOSE: The
      purpose of this systematic review was to identify similarities among treatment
      options for generalized tooth wear and to develop an approach to rehabilitation
      based on the best evidence available. MATERIAL AND METHODS: A Medline and
      Cochrane search (for articles published from January 31, 2003, to January 31,
      2013) was conducted. Minimally invasive and fully described treatments for
      generalized tooth wear with esthetically satisfying results were included. Five
      steps within the treatment procedures were analyzed: diagnostic waxing (DW),
      occlusal positioning (OP), vertical dimension increase (VDI), restoration, and
      follow-up. RESULTS: Common threads were established within the 5 treatment steps.
      Nine studies used DW, and 6 performed diagnostic tooth arrangement (DTA). Centric
      relation was used in 5 studies, and VDI was tested in 8 studies, 5 of which used
      a removable appliance. Seven studies implemented a provisional stage, and 5 used
      composite resin at that time. For definitive treatment, composite resin (6
      studies) and glass ceramic (6 studies) were used. Seven studies applied a
      protective appliance, and 5 scheduled regular posttreatment evaluation as means
      of aftercare. CONCLUSIONS: Within the limitations of this systematic review, the
      present evidence is not strong enough to form conclusions, and the presented
      similarities cannot be substantiated with evidence. Therefore, comprehensive
      clinical research into the designated treatment of generalized tooth wear is
      recommended.

PMID- 24721501
TI  - Fluoride ion release and solubility of fluoride enriched interim cements.
AB  - STATEMENT OF PROBLEM: Interim and definitive restorations cemented with interim
      cements for a prolonged interval are susceptible to bacterial infiltration and
      caries formation. PURPOSE: The purpose of this in vitro study was to evaluate the
      long-term fluoride release and solubility of aged ZnO-based interim cements
      enriched separately with 0.4% NaF and SnF2. MATERIAL AND METHODS: Four different
      brands of cements (Tempbond, Tempbond NE, Procem, and Freegenol) were tested for
      fluoride release and solubility. For every test, 6 disk specimens of each cement
      with NaF and SnF2, and 6 with no fluoride enrichment (control) were fabricated,
      for a total of 72 specimens. The disks were incubated in deionized water.
      Fluoride ion release was recorded at 1, 7, 14, 21, 63, 91, and 182 days.
      Solubility was calculated as weight percent after 90 days of incubation. The data
      were analyzed by analysis of variance with repeated measures and the Tukey
      honestly significant difference post hoc test (P<.05). RESULTS: Cements mixed
      with fluorides released fluoride ions for at least 182 days. Cements mixed with
      NaF released more fluoride ions than those mixed with SnF2 (P<.001). The
      cumulative release rates from all the tested cements mixed with either NaF or
      SnF2 were linear with respect to t(1/2) (r>.97), indicating a diffusion
      controlled fluoride release. Cement and fluoride types were the main affecting
      factors in fluoride ion release. The addition of fluorides slightly increased the
      solubility of the cements. CONCLUSIONS: Given their long-term sustained and
      diffusive controlled release, these fluorides, particularly NaF when mixed with
      ZnO-based interim cements, may be useful for caries prevention under
      provisionally cemented restorations.

PMID- 24721502
TI  - Influence of the veneer-framework interface on the mechanical behavior of ceramic
      veneers: a nonlinear finite element analysis.
AB  - STATEMENT OF PROBLEM: The chipping of ceramic veneers is a common problem for
      zirconia-based restorations and is due to the weak interface between both
      structures. PURPOSE: The purpose of this study was to evaluate the mechanical
      behavior of ceramic veneers on zirconia and metal frameworks under 2 different
      bond-integrity conditions. MATERIAL AND METHODS: The groups were created to
      simulate framework-veneer bond integrity with the crowns partially debonded
      (frictional coefficient, 0.3) or completely bonded as follows: crown with a
      silver-palladium framework cemented onto a natural tooth, ceramic crown with a
      zirconia framework cemented onto a natural tooth, crown with a silver-palladium
      framework cemented onto a Morse taper implant, and ceramic crown with a zirconia
      framework cemented onto a Morse taper implant. The test loads were 49 N applied
      to the palatal surface at 45 degrees to the long axis of the crown and 25.5 N
      applied perpendicular to the incisal edge of the crown. The maximum principal
      stress, shear stress, and deformation values were calculated for the ceramic
      veneer; and the von Mises stress was determined for the framework. RESULTS:
      Veneers with partial debonding to the framework (frictional coefficient, 0.3) had
      greater stress concentrations in all structures compared with the completely
      bonded veneers. The metal ceramic crowns experienced lower stress values than
      ceramic crowns in models that simulate a perfect bond between the ceramic and the
      framework. Frameworks cemented to a tooth exhibited greater stress values than
      frameworks cemented to implants, regardless of the material used. CONCLUSION:
      Incomplete bonding between the ceramic veneer and the prosthetic framework
      affects the mechanical performance of the ceramic veneer, which makes it
      susceptible to failure, independent of the framework material or complete crown
      support.

PMID- 24721503
TI  - Effect of polishing systems on stain susceptibility and surface roughness of
      nanocomposite resin material.
AB  - STATEMENT OF PROBLEM: Different polishing systems vary in their effect on
      reducing surface roughness and stain susceptibility of dental composite resin
      materials. PURPOSE: The purpose of this study was to compare the effect of 3
      polishing systems on the stain susceptibility and surface roughness of 2
      nanocomposite resins and a microhybrid composite resin. MATERIAL AND METHODS:
      Forty-five disks (2*10 mm) each were fabricated of 2 nanocomposite resins (Filtek
      Supreme XT and Tetric EvoCeram) and 1 microhybrid composite resin (Z250). Both
      sides of the disks were wet finished, and 1 side was polished with PoGo,
      Astropol, or Hi-Shine (n=5). Unpolished surfaces served as controls. The average
      roughness (Ra, MUm) was measured with a profilometer, and the baseline color was
      recorded with a spectrophotometer. All specimens were incubated while soaking in
      a staining solution of coffee, green tea, and berry juice for 3 weeks. The color
      was recorded again, and the data were analyzed with 2-way ANOVA at alpha=.05 and
      Tukey multiple comparison tests. RESULTS: All polishing systems improved the
      staining resistance of Filtek Supreme XT and Z250 but did not affect that of
      Tetric EvoCeram. The surface color of Filtek Supreme XT was changed significantly
      and was the smoothest after polishing with PoGo, whereas Hi-Shine produced
      significantly rougher surfaces but with the lowest color change. Hi-Shine
      produced the highest color change in Z250. The surface roughness did not differ
      significantly between the other polishing systems. Tetric EvoCeram showed no
      significant differences in color change or surface roughness. CONCLUSIONS:
      Staining susceptibility and surface roughness depend mainly on material
      composition and on the polishing procedures. Polishing improves the staining
      resistance of composite resins. Nanocomposite resins did not exhibit better
      staining resistance or surface roughness than microhybrid composite resin.

PMID- 24721504
TI  - Comparison of the flexural strength and marginal accuracy of traditional and
      CAD/CAM interim materials before and after thermal cycling.
AB  - STATEMENT OF PROBLEM: Limited information is available concerning the properties
      of computer-aided designed/computer-aided manufactured (CAD/CAM) interim
      materials. PURPOSE: The purpose of this study was to investigate the flexural
      strength and marginal accuracy of 2 traditional bis-acryl composite resin interim
      materials (Protemp 4 and Structur 2 SC/QM) and 2 CAD/CAM interim materials (Teilo
      CAD and VITA CAD-Temp). MATERIAL AND METHODS: Standard specimens (25 * 2 * 2 mm)
      of the 4 materials were made (n=20). Each group contained 10 specimens fractured
      under 3-point loading in a universal testing machine with a cross-head speed of 1
      mm/min. The other 10 specimens were subjected to 5000 thermal cycles (5 degrees C
      and 55 degrees C) before testing. Four groups of interim crowns were fabricated
      from the 4 materials on models of a prepared left maxillary first molar (n=10).
      Twenty-four hours after cementing the crowns, margin discrepancies were measured
      under a stereomicroscope. The crowns then were subjected to 5000 thermal cycles
      (5 degrees C and 55 degrees C), and the margin discrepancies were measured again.
      RESULTS: Teilo CAD showed the highest mean flexural strength of the 4 interim
      materials before and after thermal cycling, and VITA CAD-Temp showed the lowest
      (P<.05). After thermal cycling, the flexural strength decreased significantly
      (P<.05). The margin discrepancies were larger for the bis-acryl interim crowns
      than for the CAD/CAM crowns before and after thermal cycling (P<.05). After
      thermal cycling, the margin discrepancies in the bis-acryl interim crowns were
      larger (P<.05); however, no significant differences were found for the margin
      discrepancies in the CAD/CAM interim crowns (P>.05). CONCLUSIONS: CAD/CAM interim
      materials were stronger and had better marginal accuracy properties than bis
      acryl materials, especially after thermal cycling.

PMID- 24721505
TI  - A conservative approach to rebasing an implant-retained fixed complete denture.
AB  - After years of service, the acrylic resin base of an implant-retained fixed
      complete dental prosthesis may need to be replaced because of the wear of the
      acrylic resin teeth. The most common methods used by dental laboratories to
      remove the acrylic resin from the metal framework are either burning with a flame
      or grinding. Both of these methods risk exposing the dental laboratory technician
      to hazardous by-products and damaging or contaminating the metal framework or the
      gold cylinders. This article presents a safe approach to removing acrylic resin
      while preserving the integrity of the framework. The technique involves heating
      the prosthesis to beyond the glass transitional temperature of the acrylic resin
      to allow the resin to be safely peeled off the framework. 

PMID- 24721506
TI  - The effects of off-axial loading on periimplant marginal bone loss in a single
      implant.
AB  - STATEMENT OF PROBLEM: A discrepancy between crown width and implant width may
      contribute to potential bending overload. PURPOSE: The purpose of this study was
      to evaluate the influence of the crown width-fixture width ratio on crestal bone
      loss around single dental implants placed in the first molar area. MATERIAL AND
      METHODS: Seventy-six participants (37 men and 39 women; age range, 25-83 years;
      mean age [standard deviation], 56.3 +/-10.6 years) were selected from individuals
      who were treated with single tooth implants between May 2004 and December 2009 at
      the Department of Periodontology, Gangnam Severance Dental Hospital. The marginal
      bone-level change and gingival parameters (modified plaque index and modified
      sulcus bleeding index) of the periimplant soft tissue were assessed 1 year after
      functional loading. The perpendicular distances from the vertical axis of each
      fixture to the most distal aspect of the crown and most mesial aspect of the
      crown were measured in the periapical radiographic view. RESULTS: No
      statistically significant relationship was found between crown width-fixture
      width ratio and the 1-year bone-level change (Pearson correlation, P=.06;
      Spearman rank test, P=.14). No statistically significant differences in marginal
      bone-level change were found between axial and nonaxial loading implants (2
      independent samples t test; P=.19). The bone-level change for the surface
      adjacent and distant to the cantilever was not statistically significant (paired
      t test; P=.10). CONCLUSION: From this study, it may be concluded that off-axial
      loading that results from a high crown width-fixture width ratio does not
      increase the risk for periimplant marginal bone loss after 1-year functional
      loading.

PMID- 24721507
TI  - Accuracy of implant placement in the posterior maxilla as related to 2 types of
      surgical guides: a pilot study in the human cadaver.
AB  - STATEMENT OF PROBLEM: The position of implants may have an effect on obtaining
      osseointegration without complications and on the outcome of the prostheses.
      PURPOSE: The purpose of this study was to compare the accuracy of implant
      placement with computer-guided surgery and freehand surgery in the atrophic area
      of the posterior maxilla. MATERIAL AND METHODS: Six human cadavers (Kennedy
      Applegate class I) were included in the study. The specimens were randomly
      classified into 2 categories by using a computer: computer-guided surgery (n=3)
      and freehand surgery (n=3). Thirty-nine implants were planned with the software.
      Two types of surgeries were performed. The preoperative computed tomography data
      were matched with the postoperative computed tomography data by using voxel-based
      registration software. The position of the planned implants was compared to the
      actual position of the implants. A multivariate analysis was used for each
      variable (bone density, length of implant, implant angulation, and surgical
      technique) to evaluate the effect of these variables on the implant accuracy
      (alpha=.05). RESULTS: The statistical tests (Kolmogorov-Smirnov bootstrap) found
      that guided surgery offered significantly better accuracy for the platform
      (P=.002), apex (P=.001), and angle (P<.001). However, the accuracy of the 2
      methods was similar for the depth parameter (P=.186). The bone density did not
      influence the implant placement accuracy. CONCLUSIONS: Computer-guided surgery
      was more accurate than a freehand approach for placing implants into bilateral
      edentulous zones in the posterior maxilla.

PMID- 24721508
TI  - Wing geometry of Culex coronator (Diptera: Culicidae) from South and Southeast
      Brazil.
AB  - BACKGROUND: The Coronator Group encompasses Culex coronator Dyar & Knab, Culex
      camposi Dyar, Culex covagarciai Forattini, Culex ousqua Dyar, Culex usquatissimus
      Dyar, Culex usquatus Dyar and Culex yojoae Strickman. Culex coronator has the
      largest geographic distribution, occurring in North, Central and South America.
      Moreover, it is a potential vector-borne mosquito species because females have
      been found naturally infected with several arboviruses, i.e., Saint Louis
      Encephalitis Virus, Venezuelan Equine Encephalitis Virus and West Nile Virus.
      Considering the epidemiological importance of Cx. coronator, we investigated the
      wing shape diversity of Cx. coronator from South and Southeast Brazil, a method
      to preliminarily estimate population diversity. METHODS: Field-collected immature
      stages of seven populations from a large geographical area in Brazil were
      maintained in the laboratory to obtain both females and males linked with pupal
      and/or larval exuviae. For each individual female, 18 landmarks of left wings
      were marked and digitalized. After Procrustes superimposition, discriminant
      analysis of shape was employed to quantify wing shape variation among
      populations. The isometric estimator centroid size was calculated to assess the
      overall wing size and allometry. RESULTS: Wing shape was polymorphic among
      populations of Cx. coronator. However, dissimilarities among populations were
      higher than those observed within each population, suggesting populational
      differentiation in Cx. coronator. Morphological distances between populations
      were not correlated to geographical distances, indicating that other factors may
      act on wing shape and thus, determining microevolutionary patterns in Cx.
      coronator. Despite the population differentiation, intrapopulational wing shape
      variability was equivalent among all seven populations. CONCLUSION: The wing
      variability found in Cx. coronator populations brings to light a new biological
      problem to be investigated: the population genetics of Cx. coronator. Because of
      differences in the male genitalia, we also transferred Cx. yojoae to the Apicinus
      Subgroup.

PMID- 24721509
TI  - [Contribution of intraoperative scintigraphy to the detection of intrathyroidal
      parathyroid adenoma].
AB  - The intrathyroidal parathyroid adenomas (IPA) represent a rare cause of primary
      hyperparathyroidism whose location difficults appropriate surgical removal. We
      present the case of a patient diagnosed of parathyroid adenoma by presurgical
      scintigraphy in which finally during the parathyroidectomy, the lesion location
      was intrathyroidal. We consider that the intrasurgical parathyroid scintigraphy
      with (99m)Tc-MIBI by portable gammacamera is useful in the parathyroid adenomas
      removal and essential in the case of IPA. 

PMID- 24721510
TI  - [Aberrant lymphatic drainage from a melanoma located in epigastric area].

PMID- 24721512
TI  - Changes in biomechanical properties of the coronary artery wall contribute to
      maintained contractile responses to endothelin-1 in atherosclerosis.
AB  - AIMS: Our aim was to determine whether alterations in biomechanical properties of
      human diseased compared to normal coronary artery contribute to changes in artery
      responsiveness to endothelin-1 in atherosclerosis. MAIN METHODS: Concentration
      response curves were constructed to endothelin-1 in normal and diseased coronary
      artery. The passive mechanical properties of arteries were determined using
      tensile ring tests from which finite element models of passive mechanical
      properties of both groups were created. Finite element modelling of artery
      endothelin-1 responses was then performed. KEY FINDINGS: Maximum responses to
      endothelin-1 were significantly attenuated in diseased (27+/-3 mN, n=55) compared
      to normal (38+/-2 mN, n=68) artery, although this remained over 70% of control.
      There was no difference in potency (pD2 control=8.03+/-0.06; pD2 diseased=7.98+/
      0.06). Finite element modelling of tensile ring tests resulted in hyperelastic
      shear modulus MU=2004+/-410 Pa and hardening exponent alpha=22.8+/-2.2 for normal
      wall and MU=2464+/-1075 Pa and alpha=38.3+/-6.7 for plaque tissue and
      distensibility of diseased vessels was decreased. Finite element modelling of
      active properties of both groups resulted in higher muscle contractile strain
      (represented by thermal reactivity) of the atherosclerotic artery model than the
      normal artery model. The models suggest that a change in muscle response to
      endothelin-1 occurs in atherosclerotic artery to increase its distensibility
      towards that seen in normal artery. SIGNIFICANCE: Our data suggest that an
      adaptation occurs in medial smooth muscle of atherosclerotic coronary artery to
      maintain distensibility of the vessel wall in the presence of endothelin-1. This
      may contribute to the vasospastic effect of locally increased endothelin-1
      production that is reported in this condition.

PMID- 24721511
TI  - Tissue-specific and time-dependent regulation of the endothelin axis by the
      circadian clock protein Per1.
AB  - AIMS: The present study is designed to consider a role for the circadian clock
      protein Per1 in the regulation of the endothelin axis in mouse kidney, lung,
      liver and heart. Renal endothelin-1 (ET-1) is a regulator of the epithelial
      sodium channel (ENaC) and blood pressure (BP), via activation of both endothelin
      receptors, ETA and ETB. However, ET-1 mediates many complex events in other
      tissues. MAIN METHODS: Tissues were collected in the middle of murine rest and
      active phases, at noon and midnight, respectively. ET-1, ETA and ETB mRNA
      expressions were measured in the lung, heart, liver, renal inner medulla and
      renal cortex of wild type and Per1 heterozygous mice using real-time quantitative
      RT-PCR. KEY FINDINGS: The effect of reduced Per1 expression on levels of mRNAs
      and the time-dependent regulation of expression of the endothelin axis genes
      appeared to be tissue-specific. In the renal inner medulla and the liver, ETA and
      ETB exhibited peaks of expression in opposite circadian phases. In contrast,
      expressions of ET-1, ETA and ETB in the lung did not appear to vary with time,
      but ET-1 expression was dramatically decreased in this tissue in Per1
      heterozygous mice. Interestingly, ET-1 and ETA, but not ETB, were expressed in a
      time-dependent manner in the heart. SIGNIFICANCE: Per1 appears to regulate
      expression of the endothelin axis genes in a tissue-specific and time-dependent
      manner. These observations have important implications for our understanding of
      the best time of day to deliver endothelin receptor antagonists.

PMID- 24721513
TI  - Oncogenic BRAF inhibitor UAI-201 induces cell cycle arrest and autophagy in BRAF
      mutant glioma cells.
AB  - AIMS: An activating mutation of BRAF (BRAF-V600E) has been reported in a subset
      of malignant brain tumors. Thus, the aim of the present study was to identify the
      antiproliferative effect of the new oncogenic B-Raf targeting drug UAI-201 on 6
      types of glioma cell lines with differing B-Raf mutational status. MAIN METHODS:
      The IC50 values of UAI-201 were determined using crystal violet assays in six
      glioma cell lines. Real-time RT-PCR was performed to assess the functional role
      of multidrug resistance proteins in response to UAI-201. The effects of UAI-201
      on six glioma cells were further examined by immunoblotting analysis, cell cycle
      analysis, flow cytometric apoptotic assay and autophagy assay. To identify the
      role of autophagy in UAI-201-induced growth inhibition, Atg5 and Beclin 1 were
      knocked down by RNA interference. KEY FINDINGS: Real-time RT-PCR analysis showed
      a poor correlation between UAI-201 activity and the expression level of multidrug
      resistance proteins. The growth inhibitory effects of UAI-201 correlated with the
      BRAF-V600E genotype of the glioma cell lines. BRAF blockade with UAI-201 resulted
      in dose-dependent inhibition of MEK/ERK phosphorylations and increased G0/G1
      arrest in glioma cells with BRAF-V600E. Interestingly, UAI-201 preferentially
      induced autophagy in BRAF-V600E cells, but not in BRAF-WT cells. More notably,
      autophagy inhibition through siRNA-mediated Beclin 1 knockdown partially
      attenuated the growth inhibition induced by UAI-201 in BRAF-V600E cells.
      SIGNIFICANCE: The pro-death autophagic processes could be one of the underlying
      mechanisms for the sensitization of BRAF-V600E glioma cells toward UAI-201.

PMID- 24721514
TI  - Potential for daily supplementation of n-3 fatty acids to reverse symptoms of dry
      eye in mice.
AB  - The purpose of this study was to determine the change in tear volume, as a
      predominant symptom of dry eye syndrome, in dietary n-3 fatty acid deficient mice
      compared with n-3 fatty acid adequate mice. The tear volume in n-3 fatty acid
      deficient mice was significantly lower than that in n-3 fatty acid adequate mice.
      In addition, the concentration of n-3 fatty acid in the lacrimal and meibomian
      glands, which affects the production of tears, was markedly decreased compared
      with n-3 fatty acid adequate mice. However, the tear volume recovered almost
      completely after one week of continuous administration of fish oil containing EPA
      and DHA in n-3 fatty acid deficient mice. Also, the concentration of DHA in the
      meibomian gland of n-3 fatty acid deficient group recovered to approximately 80%
      more than that of n-3 fatty acid adequate group. These results suggested that
      dietary n-3 fatty acids deficiency showed reversible dry eye syndrome, and that n
      3 fatty acids have an important role in the production of tears. 

PMID- 24721516
TI  - An uncommon gastric finding: a budding problem.

PMID- 24721515
TI  - Phylogenetic and geospatial evaluation of HIV-1 subtype diversity at the largest
      HIV center in Rhode Island.
AB  - Individuals infected with HIV-1 non-B subtypes are understudied in the United
      States. Their characterization may augment prevention and treatment
      interventions. We examined the regional molecular epidemiology of non-B subtypes
      using a combined phylogenetic and geospatial approach. HIV-1 pol sequences and
      clinical data obtained for routine clinical care were aggregated from 2004 to
      2011 at the largest HIV center in Rhode Island. Subtyping was performed by
      neighbor-joining and maximum-likelihood phylogeny and compared across eight
      commonly used tools (HIVdb, REGA, RIP, NCBI, Geno2Pheno, EuResist, jpHMM and
      STAR) using proportional odds ordinal regression. Individuals with non-B subtypes
      were characterized according to demographics and risk factors for infection,
      intra-subtype clustering by maximum-likelihood phylogeny, and geospatial hotspot
      analysis using Getis-Ord Gi(*) statistics. Of 1277 unique sequences, phylogenetic
      subtyping demonstrated 8.3% (N=106, 95% CI 6.8-10%) non-B subtypes and
      circulating recombinant forms (CRFs): CRF02_AG=46; A=15; C=15; CRF01_AE=6;
      CRF06_CPX=5; CRF14_BG=5; G=3; CRF43_02G=3; D=3; CRF24_BG=3; CRF11_CPX=1; F1=1.
      Compared to phylogeny, Geno2Pheno was the most concordant (86% exact match)
      followed by REGA (85%), EuResist (85%) and STAR (82%). Of 106 individuals with
      non-B subtypes, 50% were male, 71% acquired infection through heterosexual
      transmission; 76%, were born in Africa, 6% Southeast Asia, 5% the United States,
      3% Central America, 1% Europe, and 9% unknown. Eighty percent of CRF02_AG, 93% of
      A and 87% of C sequences were from African-born individuals. Twenty-two percent
      of non-B subtypes formed transmission clusters, including a significant number of
      younger individuals with perinatally-acquired infection. Geospatial analyses
      revealed hotspots of B and non-B subtypes in the state capital with a more
      concentrated focus among non-B subtypes. Molecular examination of regional HIV
      diversity revealed a larger than expected non-subtype B infected population,
      mostly born in Africa, with low ongoing regional transmission. Phylogenetic and
      geospatial characterization of infection clusters is helpful to identify targets
      for treatment and prevention interventions. 

PMID- 24721517
TI  - A novel method for endoscopic perforation management by using abdominal
      exploration and full-thickness sutured closure.
AB  - BACKGROUND: Perforation of the GI tract during endoscopy can result in
      significant morbidity and mortality. Early recognition and immediate management
      of endoscopic perforation are essential to optimize outcome. Larger perforations,
      defects with complex geometry, and those complicated by leakage of luminal
      contents have traditionally required surgical management. OBJECTIVE: To assess
      the feasibility of a new method for managing complex perforations that
      incorporates abdominal exploration and endoscopic sutured closure. DESIGN: Case
      series. SETTING: Tertiary care center. PATIENTS: Two patients with large,
      complicated perforations and peritoneal contamination. INTERVENTIONS: Endoscopic
      exploration of abdomen with angiocatheter placement under direct visualization,
      management of leaked luminal contents, and full-thickness sutured defect closure.
      RESULTS: Endoscopic abdominal exploration through the perforation site allowed
      safe placement of an angiocatheter for management of pneumoperitoneum, inspection
      for injury that may warrant surgical management, and removal of leaked luminal
      contents. Endoscopic sutured closure allowed safe and robust perforation
      management. Repair of gastrojejunal anastomotic perforation required 2 sutures
      and 63 minutes. Repair of gastric perforation required 4 sutures and 48 minutes.
      Patients had successful endoscopic defect closure confirmed by an upper GI series
      and were discharged 1 day later. LIMITATIONS: Report of a new method in 2
      patients performed at tertiary care center. CONCLUSIONS: We demonstrate
      successful management of complex perforations with peritoneal contamination by
      incorporating endoscopic exploration and sutured closure with standard treatment
      measures. Traditional practice would have directed these patients to surgical
      management, which introduces additional morbidity and cost. A means for safe and
      broad implementation of these techniques should be evaluated.

PMID- 24721518
TI  - A newly designed fully covered metal stent for lumen apposition in EUS-guided
      drainage and access: a feasibility study (with videos).
AB  - BACKGROUND: A lumen-apposing stent can be used effectively under endosonographic
      guidance. OBJECTIVE: To evaluate a newly designed, fully covered self-expandable
      metal stent with folding anchoring flanges for lumen apposition assembled on a
      conventional delivery system. DESIGN: Retrospective case series and animal study.
      SETTING: Tertiary care academic medical centers. SUBJECTS: Six pigs for animal
      study and 7 patients, 3 of whom underwent endoscopic drainage for acute
      cholecystitis (AC) and 4 for pancreatic fluid collection (PFC). INTERVENTION:
      Stent deployment under EUS guidance after puncturing, passage of an endoscope
      through the stent into the gallbladder (GB), or PFC with conventional endoscopic
      procedures. MAIN OUTCOME MEASUREMENTS: Technical and clinical success, adverse
      events, and removability. RESULTS: In the animal study, the stent was
      successfully inserted and deployed in the GB via a transgastric approach under
      EUS guidance without adverse events in all 6 pigs. Contrast injection
      demonstrated the absence of leakage. Cholecystoscopy with enhanced endoscopy was
      performed successfully in all animals after stent placement. All stents were
      intact and were removed successfully at 4 weeks. GB firmly adhered to the stomach
      with an intact cholecystogastric tract on necropsy and histopathology. The stents
      were successfully deployed without adverse effects in 7 patients. AC or PFC was
      resolved after stent placement in all patients. Endoscopic procedures were
      possible through the stent. Stent migration was not observed. The stent was
      successfully removed from the 4 patients with PFC after complete resolution.
      LIMITATIONS: Small sample size, retrospective study. CONCLUSIONS: Transenteric
      drainage and endoscopic intervention by using a novel fully covered self
      expandable metal stent for lumen apposition under EUS guidance is feasible for
      the management of AC and PFC. Further study is warranted.

PMID- 24721519
TI  - Endoscopic transluminal drainage and necrosectomy by using a novel, through-the
      scope, fully covered, large-bore esophageal metal stent: preliminary experience
      in 10 patients.
AB  - BACKGROUND: Interventions for necrotizing pancreatitis have undergone a recent
      paradigm shift toward minimally invasive techniques, including endoscopic
      transluminal necrosectomy (ETN). The optimal stent for endoscopic transmural
      drainage remains unsettled. OBJECTIVE: To evaluate a novel large-bore, fully
      covered metal through-the-scope (TTS) esophageal stent for cystenterostomy in
      large walled-off necrosis (WON). DESIGN: Retrospective case series. SETTING:
      Single tertiary care academic center. PATIENTS: Ten patients with large (>10 cm)
      WON collections who underwent endoscopic transmural drainage and ETN.
      INTERVENTION: Initial cystenterostomy was performed by using EUS, and in the same
      session, a TTS (18 * 60 mm), fully covered esophageal stent was placed to create
      a wide-bore fistula into the cavity. In 1 or more later sessions, the stent was
      removed, and ETN was performed as needed. MAIN OUTCOME MEASUREMENTS: Technical
      and clinical success rates and adverse events. RESULTS: The TTS stent was
      successfully deployed at the initial cystogastrostomy in all 10 patients. All
      patients had large WON (median size 17 cm, range 11-30 cm) and underwent
      intervention at a median of 30 days (range 12-117 days) after onset of acute
      pancreatitis. Resolution of WON was achieved in 9 of the 10 patients (90%) after
      a median of 3 endoscopic sessions. There were no early adverse events. Late
      adverse events occurred in 3 patients (30%); worsening of infection from stent
      migration and occlusion of cystogastrostomy (2 patients), and fatal
      pseudoaneurysmal bleeding from erosion of infected necrosis into a major artery
      distant from the stent (1 patient). The stent was easily removed in all the cases
      after resolution or improvement of the necrotic cavity. LIMITATIONS:
      Retrospective, single-center evaluation of a small number of cases. No
      comparative arm to determine the relative efficacy or cost-effectiveness of these
      stents compared with conventional plastic stents. CONCLUSIONS: Endoscopic therapy
      using a large-bore TTS, fully covered esophageal stent is feasible for use in the
      treatment of large WON. Further studies are needed to validate these findings.

PMID- 24721520
TI  - Safety of endoscopic interventions in patients with thrombocytopenia.
AB  - BACKGROUND: The risk of endoscopic interventions in thrombocytopenia has received
      little attention in the medical literature. OBJECTIVE: The aim of this study was
      to assess the safety of endoscopic interventions including evaluation of GI
      bleeding (GIB) in patients with thrombocytopenia. DESIGN AND SETTING:
      Retrospective study, tertiary oncology center. PATIENTS AND INTERVENTION: Review
      of consecutive endoscopies with preprocedure platelet counts (PCs) of 75 *
      10(3)/MUL or lower. MAIN OUTCOME MEASUREMENTS: Risk of bleeding with routine
      endoscopic interventions and transfusion requirement after evaluation of GIB.
      RESULTS: A total of 617 (351 upper, 266 lower [90 colonoscopies]) endoscopies
      were performed in 395 patients. Forceps-biopsy specimens were obtained in 398
      endoscopies (mean +/- standard deviation [SD] PC: 38.21 +/- 11.7 * 10(3)/MUL) and
      45 polypectomies were performed in 17 endoscopies (mean +/- SD PC: 39.65 +/- 8.53
      * 10(3)/MUL). The risk of bleeding was 1.5% (6 of 398 endoscopies) at the biopsy
      site and 4% (2 of 45 polypectomies) at the polypectomy site. Active GIB (mean +/-
      SD PC: 32.85 +/- 4.0 * 10(3)/MUL) was observed in 68 (11% of 617) endoscopies and
      intervention (mean +/- SD PC: 33.68 +/- 4.6 * 10(3)/MUL) was performed in 41
      procedures. Together, angiodysplasias and ulcers were the most common etiology
      (51.2% of 41). Hemostasis was achieved in 39 (95.1% of 41) procedures. Comparison
      of blood transfusions +/- 3 days of successful therapy showed a 52% reduction (P
      < .001). By multivariate analysis, a higher aggregate blood transfusion 3 days
      preceding endoscopy (odds ratio 1.32; 95% confidence interval, 1.16-1.50; P <
      .001) predicted endoscopic findings of active GIB. LIMITATIONS: Retrospective
      design, single center. CONCLUSIONS: In the largest endoscopic experience reported
      in thrombocytopenic patients (Common Terminology Criteria for Adverse Events
      grade 3 or lower), bleeding caused by standard forceps biopsy and polypectomy
      (<=10 mm) was minor and easily controlled. Endoscopic therapy for GIB is safe and
      significantly reduces the packed red blood cell requirement and should be
      considered in patients with thrombocytopenia in the setting of an appropriate
      transfusion strategy.

PMID- 24721521
TI  - Comparison of a superficial suturing device with a full-thickness suturing device
      for transoral outlet reduction (with videos).
AB  - BACKGROUND: Larger gastrojejunal (GJ) anastomosis aperture is one independent
      predictor for weight regain after Roux-en-Y gastric bypass. Transoral outlet
      reduction (TORe) has proven safe and effective for treatment of weight regain by
      using a superficial-thickness (ST) suturing device. Full-thickness (FT) suturing
      devices are now available, potentially providing more effective results.
      OBJECTIVE: To compare effectiveness of superficial-thickness with full-thickness
      TORe. DESIGN: Matched cohort study: patients were matched sequentially by GJ
      anastomosis aperture, body mass index, and age. SETTING: Tertiary-care center.
      PATIENTS: A total of 59 consecutive patients undergoing full-thickness TORe were
      matched with 59 patients undergoing superficial-thickness TORe. All had GJ
      anastomosis apertures >20 mm. INTERVENTION: Transoral outlet reduction. MAIN
      OUTCOME MEASUREMENTS: Weight loss and rate of adverse events. RESULTS: Post-TORe
      GJ anastomosis apertures were similar between groups (ST 6.9 +/- 0.2 mm vs FT 7.1
      +/- 0.3 mm). Weight loss was greater at 6 months in the FT group (10.6 +/- 1.8 kg
      in FT vs 4.4 +/- 0.8 kg in ST; P < .01) and at 1 year (8.6 +/- 2.5 kg in FT vs
      2.9 +/- 1.0 kg in ST; P < .01). Excess weight loss was greater in the FT group at
      6 months (20.4 +/- 3.3% in FT vs 8.1 +/- 2.5% in ST; P < .01) and at 1 year (18.9
      +/- 5.4% in FT vs 9.1 +/- 2.3% in ST; P = .03). LIMITATIONS: This was a single
      center, retrospective, cohort study. CONCLUSION: There is level 1b evidence for
      effectiveness of TORe by using a superficial mucosal suturing device. This
      matched cohort study compared TORe by using the same ST suturing device with TORe
      by using a newer, FT suturing device and the same operative methods. FT TORe
      resulted in significantly more weight loss than ST TORe at 6 months and at 1
      year. Full-thickness TORe is a significant improvement over ST TORe for
      endoscopic therapy of weight regain in patients with dilated GJ anastomosis.

PMID- 24721522
TI  - Endoscopic sutured gastropexy: a novel technique for performing a secure
      gastrostomy (with videos).

PMID- 24721524
TI  - Cannabinoid receptors in the basolateral amygdala are involved in the
      potentiation of morphine rewarding properties in the acquisition, but not
      expression of conditioned place preference in rats.
AB  - Several studies show the role of the basolateral amygdala (BLA) in drug-seeking,
      relapse and the brain's emotional systems. Several lines of evidence indicate a
      functional interaction between opioid and endogenous cannabinoid systems. In the
      present study, we investigated the role of intra-BLA cannabinoid CB1 receptors in
      the potentiation, acquisition and expression of morphine-induced conditioned
      place preference (CPP). One-hundred and forty-two adult male Wistar rats weighing
      230-280g were bilaterally implanted by two separate cannulae into the BLA. The
      CPP paradigm was done, and conditioning score and locomotor activity were
      recorded by Ethovision software. Results showed that intra-BLA administration of
      different doses of WIN55,212-2 (1, 2 and 4mmol/0.3ul DMSO) as a cannabinoid
      receptor agonist during the conditioning phase induced place preference in
      animals that received the ineffective (2mg/kg) dose of morphine compared to
      respective control group in saline-treated animals. On the other hand, intra-BLA
      injection of the cannabinoid CB1 receptor antagonist AM251 (45 and 90umol/0.3ul
      DMSO) during the 3-day conditioning phase reduced morphine-induced CPP.
      Furthermore, microinjection of both AM251 (15, 45 and 90umol) and WIN55,212-2 (1
      4mmol), into the BLA had no effect on the expression of morphine (5mg/kg)-induced
      CPP. Our findings suggest that cannabinoid CB1 receptors in the BLA are involved
      in the development of reward-related behaviors and they can potentiate the
      rewarding effects of morphine. It seems that the glutamatergic projection from
      the BLA to the nucleus accumbens and reward-related learning in the hippocampus
      may be involved in the acquisition and expression of opioid reward-related
      behaviors in rats. 

PMID- 24721523
TI  - Effect of the Nd:YAG laser on sealer penetration into root canal surfaces: a
      confocal microscope analysis.
AB  - OBJECTIVES: The objective of this in vitro study was to evaluate the use of the
      Neodymium:Yttrium-Aluminium-Garnet (Nd:YAG) laser as part of the root canal
      treatment on the penetration of sealer into dentinal tubules. METHODS: Eighty
      extracted lower premolars were randomly assigned to two groups (n=40 each):
      Control group (CG), subjected to a conventional protocol of endodontic
      instrumentation and obturation; and Laser group (LG), in which Nd:YAG laser
      irradiations were combined with conventional preparation and obturation.
      Endodonted samples were sectioned at 3 and 5 mm from the apex and observed under
      a confocal scanning microscope (CLSM). The penetration depth into the dentinal
      tubules and the extension of the intracanal perimeter infiltrated by sealer were
      measured. The Student-Newman-Keuls test was run for between-group comparisons
      (alpha=.05). RESULTS: The depth of sealer penetration into dentinal tubules did
      not differ among groups. LG samples showed the significantly highest percentage
      of penetrated perimeter at 3 mm from the root apex. Within each group, the
      greatest depth of penetration (P=.0001), and the major percentage of penetrated
      perimeter (P<.001), were recorded at 5 mm. CONCLUSIONS: The application of the
      Nd:YAG laser after instrumentation did not improve the depth of sealer
      penetration into the dentinal tubules. The laser enlarged the total penetrable
      perimeter near the apex. CLINICAL SIGNIFICANCE: The Nd:YAG laser may be an
      appropriate complement in root canal treatment, as it enhances the sealer
      adaptation to the dentinal walls in the proximity of the apex.

PMID- 24721525
TI  - Directed neurite growth of rat dorsal root ganglion neurons and increased
      colocalization with Schwann cells on aligned poly(methyl methacrylate)
      electrospun nanofibers.
AB  - Electrospun nanofibers are promising scaffolds for peripheral and central nervous
      system repair. The aim of this study was to examine the details of neurite growth
      of rat dorsal root ganglion neurons (DRGn) on randomly oriented and aligned
      poly(methyl methacrylate) (PMMA) nanofibers and the relationship between neurites
      and nanofibers on each substrate. Our substrate design involved electrospinning
      PMMA nanofibers directly onto bare glass coverslips with acceptable
      biocompatibility. We cocultured DRGn and Schwann cells on PMMA nanofibers and
      evaluated their response to each substrate. Compared with neurons cultured on
      PMMA film and randomly oriented nanofibers, DRGn on aligned PMMA nanofibers
      formed longer, parallel neurites in accordance with the orientation of the
      substrate nanofibers, although the average neurite number did not differ among
      the three groups. Regarding the relationship between neurites and nanofibers, the
      neurites of DRGn were in close contact with the substrate nanofibers, and the
      neurites seemed to follow aligned nanofibers more than randomly oriented
      nanofibers. Coculturing DRGn and Schwann cells on PMMA nanofibers revealed that
      on aligned nanofibers, neurites and Schwann cells had a higher chance of
      colocalization than on randomly oriented nanofibers or film; this colocalization
      may be beneficial during the process of myelination that follows. The results of
      this study enhance our understanding of the ability of aligned electrospun
      nanofibers to provide contact guidance to neural cells and strengthen the
      rationale for future in vivo studies. 

PMID- 24721527
TI  - Midlife stroke risk and cognitive decline.

PMID- 24721526
TI  - The cerebrospinal fluid "Alzheimer profile": easily said, but what does it mean?
AB  - BACKGROUND: We aimed to identify the most useful definition of the "cerebrospinal
      fluid Alzheimer profile," based on amyloid-beta1-42 (Abeta42), total tau, and
      phosphorylated tau (p-tau), for diagnosis and prognosis of Alzheimer's disease
      (AD). METHODS: We constructed eight Alzheimer profiles with previously published
      combinations, including regression formulas and simple ratios. We compared their
      diagnostic accuracy and ability to predict dementia due to AD in 1385 patients
      from the Amsterdam Dementia Cohort. Results were validated in an independent
      cohort (n = 1442). RESULTS: Combinations outperformed individual biomarkers.
      Based on the sensitivity of the best performing regression formulas, cutoffs were
      chosen at 0.52 for the tau/Abeta42 ratio and 0.08 for the p-tau/Abeta42 ratio.
      Ratios performed similar to formulas (sensitivity, 91%-93%; specificity, 81%
      84%). The same combinations best predicted cognitive decline in mild cognitive
      impairment patients. Validation confirmed these results, especially regarding the
      tau/Abeta42 ratio. CONCLUSIONS: A tau/Abeta42 ratio of >0.52 constitutes a robust
      cerebrospinal fluid Alzheimer profile. We recommend using this ratio to combine
      biomarkers.

PMID- 24721528
TI  - Leisure-time physical activity from mid- to late life, body mass index, and risk
      of dementia.
AB  - BACKGROUND: Physical activity may be beneficial for cognition, but the effect may
      vary depending on personal characteristics. METHODS: We investigated the
      associations between leisure-time physical activity (LTPA) from mid- to late
      life, the risk of dementia, and the role of body mass index, sex, and APOE in the
      CAIDE study during 28-year follow-up. Cognitive function of a random subsample
      was assessed at a mean age of 78.8 years (n = 1511), and dementia/Alzheimer's
      disease (AD) diagnoses were identified from national registers for the entire
      target population (n = 3559). RESULTS: Moderate (hazard ratio [HR], 1.46; 95%
      confidence interval [CI], 1.08-1.99) and low levels of midlife LTPA (HR, 1.39;
      95% CI, 0.99-1.95) were associated with higher risk of dementia in comparison
      with the most active category. The benefits were more pronounced among men,
      overweight individuals, and APOE epsilon4 noncarriers. Maintaining high LTPA (HR,
      0.16; 95% CI, 0.06-0.41) or increasing LTPA (HR, 0.19; 95% CI, 0.09-0.40) after
      midlife was associated with lower dementia risk. Similar results were observed
      for AD. CONCLUSIONS: The window of opportunity for preventive physical activity
      interventions may extend from midlife to older ages.

PMID- 24721529
TI  - Decomposing socioeconomic inequality in child vaccination: results from Ireland.
AB  - BACKGROUND: There is limited knowledge of the extent of or factors underlying
      inequalities in uptake of childhood vaccination in Ireland. This paper aims to
      measure and decompose socioeconomic inequalities in childhood vaccination in the
      Republic of Ireland. METHODS: The analysis was performed using data from the
      first wave of the Growing Up in Ireland survey, a nationally representative
      survey of the carers of over 11,000 nine-month old babies collected in 2008 and
      2009. Multivariate analysis was conducted to explore the child and parental
      factors, including socioeconomic factors that were associated with non
      vaccination of children. A concentration index was calculated to measure
      inequality in childhood vaccination. Subsequent decomposition analysis identified
      key factors underpinning observed inequalities. RESULTS: Overall the results
      confirm a strong socioeconomic gradient in childhood vaccination in the Republic
      of Ireland. Concentration indices of vaccination (CI=-0.19) show a substantial
      pro-rich gradient. Results from the decomposition analysis suggest that a
      substantial proportion of the inequality is explained by household level
      variables such as socioeconomic status, household structure, income and
      entitlement to publicly funded care (29.9%, 24% 30.6% and 12.9% respectively).
      Substantial differences are also observed between children of Irish mothers and
      immigrant mothers from developing countries. CONCLUSIONS: Vaccination was less
      likely in lower than in higher income households. Access to publicly funded
      services was an important factor in explaining inequalities.

PMID- 24721530
TI  - The adjuvant component alpha-tocopherol triggers via modulation of Nrf2 the
      expression and turnover of hypocretin in vitro and its implication to the
      development of narcolepsy.
AB  - BACKGROUND: After the H1N1 swine flu vaccination campaign an increased number of
      narcolepsy cases in children and adolescents was observed in Scandinavian and
      later in further European countries that correlated with the vaccination by an
      AS03-adjuvanted influenza vaccine (Pandemrix). Narcolepsy is a chronic sleep
      disorder characterized by the loss of hypocretin in the cerebrospinal fluid due
      to selective destruction of hypocretin-producing neurons in the perifornical
      hypothalamus. In >99% of the cases narcolepsy is associated with the HLA-subtype
      DQB1*602 giving the link to an autoimmune process. In contrast to other squalene
      based adjuvants, for which no association with narcolepsy was reported so far,
      ASO3 contains in addition alpha-tocopherol. It could be observed recently that
      alpha-tocopherol activates the transcription factor Nrf2. Nrf2 triggers the
      expression of cytoprotective genes, i.e. the catalytic active subunits of the
      constitutive proteasome, by binding to the antioxidant response element (ARE). It
      was hypothesized that alpha-tocopherol via activation of Nrf2 affects expression
      and turnover of hypocretin, leading to an increased amount of hypocretinalpha
      specific fragments that bind to DQB1*602. RESULTS: alpha-Tocopherol activates
      Nrf2 in neuronal cells in vitro. Promoter analysis revealed an ARE sequence in
      the hypocretin promoter. Indeed, alpha-tocopherol increases by activation of Nrf2
      the expression of hypocretin. In parallel, alpha-tocopherol -dependent induction
      of Nrf2 augments expression of catalytic subunits of the proteasome leading to
      increased degradation of hypocretin. Moreover, elevated activation of Nrf2 is
      associated with a decreased activity of NF-kappaB that results in an increased
      sensitivity to apoptotic stimuli. CONCLUSION: In case of a genetic predisposition
      (DQB1*602) alpha-tocopherol could confer to development of narcolepsy by
      activation of Nrf2 that finally leads to an elevated formation of longer
      hypocretin-derived fragments that can be presented by HLA-subtype DQB1*602. These
      cells are recognized by the immune system and due to their increased sensitivity
      to apoptotic stimuli they can be destroyed, finally leading to a lack of
      hypocretin.

PMID- 24721532
TI  - Hemozoin is a potent adjuvant for hemagglutinin split vaccine without
      pyrogenicity in ferrets.
AB  - BACKGROUND: Synthetic hemozoin (sHZ, also known as beta-hematin) from monomeric
      heme is a particle adjuvant which activates antigen-presenting cells (APCs), such
      as dendritic cells and macrophages, and enhances humoral immune responses to
      several antigens, including ovalbumin, human serum albumin, and serine repeat
      antigen 36 of Plasmodium falciparum. In the present study, we evaluated the
      adjuvanticity and pyrogenicity of sHZ as an adjuvant for seasonal trivalent
      hemagglutinin split vaccine (SV) for humans using the experimental ferret model.
      METHOD: Ferrets were twice immunized with trivalent SV, SV with sHZ (SV/sHZ) or
      Fluad, composed of trivalent SV with MF59. Serum hemagglutination inhibition (HI)
      titers against three viral hemagglutinin (HA) antigens were measured at every
      week after the immunization. The pyrogenicity of SV/sHZ was examined by
      monitoring the body temperature of the immunized ferrets. To evaluate the
      protective efficacy of SV/sHZ, the immunized ferrets were challenged with
      influenza virus B infection, followed by measurement of viral titers in the nasal
      cavity and body temperature. RESULTS: sHZ enhanced HI titers against three viral
      HA antigens in a dose-dependent manner, to an extent comparable to that of Fluad.
      The highest dose of sHZ (800 MUg) immunized with SV conferred sterile protection
      against infection with heterologous Influenza B virus, without causing any
      pyrogenic reaction such as high fever. CONCLUSION: In the present study, sHZ
      enhanced the protective efficacy of SV against influenza infection without
      inducing pyrogenic reaction, suggesting sHZ to be a promising adjuvant candidate
      for human SV.

PMID- 24721531
TI  - Sendai virus-based RSV vaccine protects against RSV challenge in an in vivo
      maternal antibody model.
AB  - Respiratory syncytial virus (RSV) is the cause of significant morbidity and
      mortality among infants, and despite decades of research there remains no
      licensed vaccine. SeVRSV is a Sendai virus (SeV)-based live intranasal vaccine
      that expresses the full length RSV fusion (F) gene. SeV is the murine counterpart
      of human parainfluenza virus type 1. Given that the target population of SeVRSV
      is young infants, we questioned whether maternal antibodies typical of this age
      group would inhibit SeVRSV vaccine efficacy. After measuring SeV- and RSV
      specific serum neutralizing antibody titers in human infants, we matched these
      defined titers in cotton rats by the passive transfer of polyclonal or monoclonal
      antibody products. Animals were then vaccinated with SeVRSV followed by a 3 month
      rest period to allow passively transferred antibodies to wane. Animals were
      finally challenged with RSV to measure the de novo vaccine-induced immune
      responses. Despite the presence of passively-transferred serum neutralizing
      antibodies at the time of vaccination, SeVRSV induced immune responses that were
      protective against RSV challenge. The data encourage advancement of SeVRSV as a
      candidate vaccine for the protection of children from morbidity and mortality
      caused by RSV. 

PMID- 24721533
TI  - Peptide-pulsed dendritic cells induce the hepatitis C viral epitope-specific
      responses of naive human T cells.
AB  - Hepatitis C virus (HCV) is a major cause of liver disease. Spontaneous resolution
      of infection is associated with broad, MHC class I- (CD8(+)) and class II
      restricted (CD4(+)) T cell responses to multiple viral epitopes. Only 20% of
      patients clear infection spontaneously, however, most develop chronic disease.
      The response to chemotherapy varies; therapeutic vaccination offers an additional
      treatment strategy. To date, therapeutic vaccines have demonstrated only limited
      success in clinical trials. Vector-mediated vaccination with multi-epitope
      expressing DNA constructs provides an improved approach. Highly-conserved, HLA-A2
      restricted HCV epitopes and HLA-DRB1-restricted immunogenic consensus sequences
      (ICS, each composed of multiple overlapping and highly conserved epitopes) were
      predicted using bioinformatics tools and synthesized as peptides. HLA binding
      activity was determined in competitive binding assays. Immunogenicity and the
      ability of each peptide to stimulate naive human T cell recognition and IFN-gamma
      production were assessed in cultures of total PBMCs and in co-cultures composed
      of peptide-pulsed dendritic cells (DCs) and purified T lymphocytes, cell
      populations derived from normal blood donors. Essentially all predicted HLA-A2
      restricted epitopes and HLA-DRB1-restricted ICS exhibited HLA binding activity
      and the ability to elicit immune recognition and IFN-gamma production by naive
      human T cells. The ability of DCs pulsed with these highly-conserved HLA-A2- and 
      DRB1-restricted peptides to induce naive human T cell reactivity and IFN-gamma
      production ex vivo demonstrates the potential efficacy of a multi-epitope-based
      HCV vaccine targeted to dendritic cells. 

PMID- 24721534
TI  - Chemically induced Salmonella enteritidis ghosts as a novel vaccine candidate
      against virulent challenge in a rat model.
AB  - Salmonella enteritidis ghosts (SEGs), non-living empty bacterial cell envelopes
      were generated by using the minimum inhibitory concentration (MIC) of sodium
      hydroxide (NaOH) and investigated as a vaccine candidate in rats. To determine
      the immunogenicity and protective efficacy of SEG vaccine, rats were divided into
      four groups: group A (non-vaccinated control), group B (orally vaccinated), group
      C (intramuscularly vaccinated) and group D (intramuscularly vaccinated with
      complete Freund's adjuvant). Vaccination of rats with SEGs induced significant
      immune responses before and after virulent challenge. Rats vaccinated with SEGs
      showed significant increases in serum IgG antibodies after challenging with
      virulent S. enteritidis on week 8 and week 10 (P<0.01). During the vaccination
      period, groups B, C and D showed significantly higher serum bactericidal activity
      (SBA) compared to group A (P<0.01). Most importantly, bacterial loads in
      vaccinated groups were significantly lower than in the non-vaccinated group
      (P<0.01). In conclusion, these results show that the chemically induced SEGs as a
      vaccine candidate against virulent challenge. 

PMID- 24721535
TI  - Integrated surveillance for prevention and control of emerging vector-borne
      diseases in Europe.

PMID- 24721536
TI  - Emergence of chikungunya fever on the French side of Saint Martin island, October
      to December 2013.

PMID- 24721537
TI  - Importance of case definition to monitor ongoing outbreak of chikungunya virus on
      a background of actively circulating dengue virus, St Martin, December 2013 to
      January 2014.

PMID- 24721538
TI  - Evidence of perinatal transmission of Zika virus, French Polynesia, December 2013
      and February 2014.

PMID- 24721539
TI  - Chikungunya outbreak in the Caribbean region, December 2013 to March 2014, and
      the significance for Europe.

PMID- 24721540
TI  - West Nile virus outbreak in humans, Greece, 2012: third consecutive year of local
      transmission.

PMID- 24721541
TI  - Epidemiology of tick-borne encephalitis in Switzerland, 2005 to 2011.

PMID- 24721544
TI  - Evidence for field cancerisation treatment of actinic keratoses with topical
      diclofenac in hyaluronic acid.
AB  - Actinic keratosis (AK) is a common skin disease seen in daily practice. It is
      associated with a risk of progression to invasive squamous cell carcinoma and can
      be regarded as a marker of increased risk for non-melanoma skin cancer. The use
      of a field-directed treatment approach reflects the need to initiate early
      treatment over an affected area to prevent tumour development and local
      recurrence. Candidate field-directed treatments require a mechanism of action
      compatible with an effect on field cancerisation, immediate and long-term
      efficacy against visible lesions and efficacy against subclinical AK.
      Applicability to large treatment areas, tolerability compatible with long-term
      use, utility in organ transplant patients and, ideally, evidence of extended long
      term activity may also be desirable. We review the evidence of a role for topical
      diclofenac sodium 3% administered in a 2.5% hyaluronic acid gel (diclofenac/HA)
      as field-directed treatment. Diclofenac/HA directly targets AK pathophysiology
      through multiple mechanisms, including induction of apoptosis, inhibition of
      angiogenesis and reduced inflammation. Clearance of visible field cancerisation
      is safely and rapidly achieved with a 90-day treatment course in patients with
      affected areas of up to 50 cm(2) and is associated with a >=75% reduction in
      target lesion number score in 85% and 91% of patients, respectively, at 30 days
      and 1 year post-treatment. Following treatment of AK in high-risk transplant
      patients, 45% remained free of lesions in the treatment area at 2 years post
      treatment. We conclude that diclofenac/HA fulfils most criteria necessary to be
      considered an appropriate candidate for a field-directed treatment in AK.

PMID- 24721546
TI  - Recommendation for a contouring method and atlas of organs at risk in
      nasopharyngeal carcinoma patients receiving intensity-modulated radiotherapy.
AB  - BACKGROUND AND PURPOSE: To recommend contouring methods and atlas of organs at
      risk (OARs) for nasopharyngeal carcinoma (NPC) patients receiving intensity
      modulated radiotherapy, in order to help reach a consensus on interpretations of
      OARs delineation. METHODS AND MATERIALS: Two to four contouring methods for the
      middle ear, inner ear, temporal lobe, parotid gland and spinal cord were
      identified via systematic literature review; their volumes and dosimetric
      parameters were compared in 41 patients. Areas under the receiver operating
      characteristic curves for temporal lobe contouring were compared in 21 patients
      with unilateral temporal lobe necrosis (TLN). RESULTS: Various contouring methods
      for the temporal lobe, middle ear, inner ear, parotid gland and spinal cord lead
      to different volumes and dosimetric parameters (P<0.05). For TLN, D1 of PRV was
      the most relevant dosimetric parameter and 64Gy was the critical point. We
      suggest contouring for the temporal lobe, middle ear, inner ear, parotid gland
      and spinal cord. A CT-MRI fusion atlas comprising 33 OARs was developed.
      CONCLUSIONS: Different dosimetric parameters may hinder the dosimetric research.
      The present recommendation and atlas, may help reach a consensus on subjective
      interpretation of OARs delineation to reduce inter-institutional differences in
      NPC patients.

PMID- 24721545
TI  - Epac contributes to cardiac hypertrophy and amyloidosis induced by radiotherapy
      but not fibrosis.
AB  - BACKGROUND: Cardiac toxicity is a side-effect of anti-cancer treatment including
      radiotherapy and this translational study was initiated to characterize radiation
      induced cardiac side effects in a population of breast cancer patients and in
      experimental models in order to identify novel therapeutic target. METHODS: The
      size of the heart was evaluated in CO-HO-RT patients by measuring the Cardiac
      Contact-Distance before and after radiotherapy (48months of follow-up). In
      parallel, fibrogenic signals were studied in a severe case of human radiation
      induced pericarditis. Lastly, radiation-induced cardiac damage was studied in
      mice and in rat neonatal cardiac cardiomyocytes. RESULTS: In patients, time
      dependent enhancement of the CCD was measured suggesting occurrence of cardiac
      hypertrophy. In the case of human radiation-induced pericarditis, we measured the
      activation of fibrogenic (CTGF, RhoA) and remodeling (MMP2) signals. In
      irradiated mice, we documented decreased contractile function, enlargement of the
      ventricular cavity and long-term modification of the time constant of decay of
      Ca(2+) transients. Both hypertrophy and amyloid deposition were correlated with
      the induction of Epac-1; whereas radiation-induced fibrosis correlated with
      Rho/CTGF activation. Transactivation studies support Epac contribution in
      hypertrophy stimulation and showed that radiotherapy and Epac displayed specific
      and synergistic signals. CONCLUSION: Epac-1 has been identified as a novel
      regulator of radiation-induced hypertrophy and amyloidosis but not fibrosis in
      the heart.

PMID- 24721547
TI  - Antibiotic stewardship in dermatology: limiting antibiotic use in acne.
AB  - BACKGROUND/OBJECTIVES: Widespread use of antibiotics in all areas of medicine has
      led to significant problems with antimicrobial resistance, which have begun to
      compromise the usefulness of antibiotics. Antibiotics have long been a keystone
      of acne therapy. There is a large population of patients with acne and antibiotic
      therapy is often used for long durations; thus, acne therapy results in extensive
      antibiotic exposure. This article discusses the role of antibiotic therapy in
      acne from the perspective of how clinicians can best preserve the utility of
      these important drugs while providing efficacious and safe therapy for acne
      patients. METHODS: Review of literature augmented by expert opinion when
      literature was sparse. RESULTS: Antibiotic monotherapy (topical or oral) is not
      recommended due to the availability of clinically superior regimens. Systemic
      antibiotics are important for managing moderate to severe acne and should be used
      for a limited duration of time (3-4 months). Topical antibiotics should be paired
      with benzoyl peroxide to limit potential for resistance. Information gained in
      recent years about the pathophysiology of acne has shed light on the role of
      Propionibacterium acnes as well as other key pathogenic pathways such as
      inflammation. CONCLUSIONS: The improved understanding of acne pathogenic
      mechanisms can and should be applied to develop modern therapeutic approaches
      that are efficacious and mesh with current public health concerns.

PMID- 24721549
TI  - Comparison of oxidative stress in four Tillandsia species exposed to cadmium.
AB  - This is first study comparing four morphologically variable species of the genus
      Tillandsia and therefore various responses to the cadmium (Cd) action were
      expected. In accordance, Cd accumulation increased in order Tillandsia
      fasciculata < Tillandsia brachycaulos < Tillandsia pruinosa < Tillandsia
      capillaris, reaching 29.6 and 197.4 MUg g(-1) DW in first and last species after
      watering with 2 MUM Cd(2+) solution over 30 days. Fluorescence visualization of
      oxidative stress confirmed increase in ROS and especially elevation in
      hydroperoxides though no visible symptoms appeared on the plants. At the same
      time, nitric oxide generation and nitroso-glutathione depletion by Cd treatment
      were typically observed. Fluorescence staining of Cd using two dyes (PhenGreen
      and Leadmium) showed that Leadmium fits better with AAS quantification. Macro-
      and micro-nutrients were not considerably affected except for zinc. Reduced
      glutathione content was the highest in control T. fasciculata while oxidized
      glutathione in T. capillaris. Ascorbic acid amount revealed extreme quantitative
      differences among species and decreased in T. fasciculata only. Free amino acids
      accumulation was similar among species except for T. capillaris and Cd caused
      both depletion and increase but without high quantitative differences. Data are
      explanatively discussed in the context of limited literature related to oxidative
      stress in epiphytic plants and with general responses of plants to cadmium/heavy
      metals.

PMID- 24721548
TI  - Cuticular differences associated with aridity acclimation in African malaria
      vectors carrying alternative arrangements of inversion 2La.
AB  - BACKGROUND: Principal malaria vectors in Africa, An. gambiae and An. coluzzii,
      share an inversion polymorphism on the left arm of chromosome 2 (2La/2L+a) that
      is distributed non-randomly in the environment. Genomic sequencing studies
      support the role of strong natural selection in maintaining steep clines in 2La
      inversion frequency along environmental gradients of aridity, and physiological
      studies have directly implicated 2La in heat and desiccation tolerance, but the
      precise genetic basis and the underlying behavioral and physiological mechanisms
      remain unknown. As the insect cuticle is the primary barrier to water loss,
      differences in cuticle thickness and/or epicuticular waterproofing associated
      with alternative 2La arrangements might help explain differences in desiccation
      resistance. METHODS: To test that hypothesis, two subcolonies of both An. gambiae
      and An. coluzzii were established that were fixed for alternative 2La
      arrangements (2La or 2L+a) on an otherwise homosequential and shared genetic
      background. Adult mosquitoes reared under controlled environmental conditions
      (benign or arid) for eight days post-eclosion were collected and analyzed.
      Measurements of cuticle thickness were made based on scanning electron
      microscopy, and cuticular hydrocarbon (CHC) composition was evaluated by gas
      chromatography-mass spectrometry. RESULTS: After removing the allometric effects
      of body weight, differences in mean cuticle thickness were found between
      alternative 2La karyotypes, but not between alternative environments. Moreover,
      the thicker cuticle of the An. coluzzii 2La karyotype was contrary to the known
      higher rate of water loss of this karyotype relative to 2L+a. On the other hand,
      quantitative differences in individual CHCs and overall CHC profiles between
      alternative karyotypes and environmental conditions were consistent with
      expectation based on previous physiological studies. CONCLUSIONS: Our results
      suggest that alternative arrangements of the 2La inversion are associated with
      differences in cuticle thickness and CHC composition, but that only CHC
      composition appears to be relevant for desiccation resistance. Differences in the
      CHC composition were consistent with previous findings of a lower rate of water
      loss for the 2L+a karyotype at eight days post-eclosion, suggesting that CHC
      composition is an important strategy for maintaining water balance in this
      genetic background, but not for 2La. Despite a higher rate of water loss at eight
      days, higher body water content of the 2La karyotype confers a level of
      desiccation resistance equivalent to that of the 2L+a karyotype.

PMID- 24721550
TI  - Molecular cloning and characterization of a novel adenylyl cyclase gene, HpAC1,
      involved in stress signaling in Hippeastrum x hybridum.
AB  - Adenylyl cyclases (ACs) are enzymes that generate cyclic AMP, which is involved
      in different physiological and developmental processes in a number of organisms.
      Here, we report the cloning and characterization of a new plant adenylyl cyclases
      (AC) gene, designated HpAC1, from Hippeastrum x hybridum. This gene encodes a
      protein of 206 amino acids with a calculated molecular mass of 23 kD and an
      isoelectric point of 5.07. The predicted amino acid sequence contains all the
      typical features of and shows high identity with putative plant ACs. The
      purified, recombinant HpAC1 is able to convert ATP to cAMP. The complementation
      test that was performed to analyze the ability of HpAC1 to compensate for the AC
      deficiency in the Escherichia coli SP850 strain revealed that HpAC1 functions as
      an adenylyl cyclase and produces cyclic AMP. Moreover, it was shown that the
      transcript level of HpAC1 and cyclic AMP concentration changed during certain
      stress conditions. Both mechanical damage and Phoma narcissi infection lead to
      two sharp increases in HpAC1 mRNA levels during a 72-h test cycle. Changes in
      intracellular cAMP level were also observed. These results may indicate the
      participation of a cAMP-dependent pathway both in rapid and systemic reactions
      induced after disruption of symplast and apoplast continuity.

PMID- 24721551
TI  - The association between zolpidem and infection in patients with sleep
      disturbance.
AB  - OBJECTIVE: Recent case reports suggest that zolpidem usage may be associated with
      infection events. The aim of this study was to determine the risk of infection
      events in patients with sleep disturbance taking zolpidem in a full 3-year follow
      up study. METHODS: A total of 17474 subjects with a diagnosis of sleep
      disturbance in 2002 and 2003 were identified, of whom 5882 had used zolpidem
      after recruitment. A Cox proportional hazard model was used to estimate the 3
      year infection event-free rates for the patients using zolpidem and those not
      using zolpidem after adjusting for confounding factors. To maximize case
      ascertainment, only patients hospitalized for infection events were included.
      RESULTS: A total of 646 patients had had infection events, 331 (5.63%) of whom
      had been taking zolpidem and 315 (2.71%) had not. Zolpidem usage increased the
      risk of infection events. After adjustments for gender, age, co-morbidities, and
      other medications, patients using zolpidem with cDDD 1-28, 29-84, and >84 had
      hazard ratios of 1.67 (95% CI, 1.32-2.11), 1.91 (95% CI, 1.47-2.49) and 1.62 (95%
      CI, 1.32-1.98) respectively, compared with patients who did not use zolpidem.
      CONCLUSIONS: Zolpidem increased the risk of infection events in sleep disturbance
      patients. This increased risk of infection should be explained to sleep
      disturbance patients, and prescriptions of zolpidem to chronic insomnia patients
      should be restricted.

PMID- 24721552
TI  - Reporting sensitivity and specificity for suicide risk instruments: a comment on.

PMID- 24721553
TI  - A nonsmooth two-sex population model.
AB  - This paper considers a two-dimensional logistic model to study populations with
      two genders. The growth behavior of a population is guided by two coupled
      ordinary differential equations given by a non-differentiable vector field whose
      parameters are the secondary sex ratio (the ratio of males to females at time of
      birth), inter-, intra- and outer-gender competitions, fertility and mortality
      rates and a mating function. For the case where there is no inter-gender
      competition and the mortality rates are negligible with respect to the density
      dependent mortality, using geometrical techniques, we analyze the singularities
      and the basin of attraction of the system, determining the relationships between
      the parameters for which the system presents an equilibrium point. In particular,
      we describe conditions on the secondary sex ratio and discuss the role of the
      average number of female sexual partners of each male for the conservation of a
      two-sex species. 

PMID- 24721554
TI  - Virtual pharmacokinetic model of human eye.
AB  - A virtual pharmacokinetic 3D model of the human eye is built using Comsol
      Multiphysics(r) software, which is based on the Finite Element Method (FEM). The
      model considers drug release from a polymer patch placed on sclera. The model
      concentrates on the posterior part of the eye, retina being the target tissue,
      and comprises the choroidal blood flow, partitioning of the drug between
      different tissues and active transport at the retina pigment epithelium (RPE)
      choroid boundary. Although most straightforward, in order to check the mass
      balance, no protein binding or metabolism is yet included. It appeared that the
      most important issue in obtaining reliable simulation results is the finite
      element mesh, while time stepping has hardly any significance. Simulations were
      extended to 100,000 s. The concentration of a drug is shown as a function of time
      at various points of retina, as well as its average value, varying several
      parameters in the model. This work demonstrates how anybody with basic knowledge
      of calculus is able to build physically meaningful models of quite complex
      biological systems.

PMID- 24721555
TI  - Epidemics on a weighted network with tunable degree-degree correlation.
AB  - We propose a weighted version of the standard configuration model which allows
      for a tunable degree-degree correlation. A social network is modeled by a
      weighted graph generated by this model, where the edge weights indicate the
      intensity or type of contact between the individuals. An inhomogeneous Reed-Frost
      epidemic model is then defined on the network, where the inhomogeneity refers to
      different disease transmission probabilities related to the edge weights. By
      tuning the model we study the impact of different correlation patterns on the
      network and epidemics therein. Our results suggest that the basic reproduction
      number R0 of the epidemic increases (decreases) when the degree-degree
      correlation coefficient rho increases (decreases). Furthermore, we show that such
      effect can be amplified or mitigated depending on the relation between degree and
      weight distributions as well as the choice of the disease transmission
      probabilities. In addition, for a more general model allowing additional
      heterogeneity in the disease transmission probabilities we show that rho can have
      the opposite effect on R0. 

PMID- 24721556
TI  - Molecular cloning of heat shock protein 10 (Hsp10) and 60 (Hsp60) cDNAs and their
      expression analysis under thermal stress in the sea cucumber Apostichopus
      japonicus.
AB  - Hsp10 and Hsp60 are important heat shock proteins (HSPs), which might be
      indispensable in the heat shock response and many other physiological processes.
      We obtained full-length cDNAs of genes hsp10 and hsp60 and classified their mRNA
      expression levels under thermal stress in the sea cucumber Apostichopus
      japonicus. Full-length hsp10 cDNA was 1528 bp containing a 5' untranslated region
      (UTR) of 83 bp, a 3' UTR of 1133 bp and an open reading frame (ORF) of 312 bp
      encoding 103 amino acid residues. Full-length hsp60 cDNA was 2560 bp containing a
      118-bp 5' UTR, a 678-bp 3' UTR and a 1764-bp ORF encoding 586 amino acid
      residues. The deduced amino acid sequences of Hsp10 and Hsp60 shared the highest
      identity with sequences of the sea urchin Strongylocentrotus purpuratus, and
      phylogenetic trees showed that the evolution of Hsp10 and Hsp60 was almost in
      accord with the evolution of species. Further analysis by real-time PCR showed
      that the expression of hsp10 and hsp60 mRNA was highly up-regulated at 26 
      degrees C compared with other three groups (20, 22, 24  degrees C), and their
      expression in the intestine was in a time-dependent manner at 26  degrees C. The
      results suggested that hsp10 and hsp60 were involved in the heat-shock response
      in the sea cucumber A. japonicus.

PMID- 24721557
TI  - The cost-utility of open prostatectomy compared with active surveillance in early
      localised prostate cancer.
AB  - BACKGROUND: There is an on-going debate about whether to perform surgery on early
      stage localised prostate cancer and risk the common long term side effects such
      as urinary incontinence and erectile dysfunction. Alternatively these patients
      could be closely monitored and treated only in case of disease progression
      (active surveillance). The aim of this paper is to develop a decision-analytic
      model comparing the cost-utility of active surveillance (AS) and radical
      prostatectomy (PE) for a cohort of 65 year old men with newly diagnosed low risk
      prostate cancer. METHODS: A Markov model comparing PE and AS over a lifetime
      horizon was programmed in TreeAge from a German societal perspective. Comparative
      disease specific mortality was obtained from the Scandinavian Prostate Cancer
      Group trial. Direct costs were identified via national treatment guidelines and
      expert interviews covering in-patient, out-patient, medication, aids and remedies
      as well as out of pocket payments. Utility values were used as factor weights for
      age specific quality of life values of the German population. Uncertainty was
      assessed deterministically and probabilistically. RESULTS: With quality
      adjustment, AS was the dominant strategy compared with initial treatment. In the
      base case, it was associated with an additional 0.04 quality adjusted life years
      (7.60 QALYs vs. 7.56 QALYs) and a cost reduction of ?6,883 per patient (2011
      prices). Considering only life-years gained, PE was more effective with an
      incremental cost-effectiveness ratio of ?96,420/life year gained. Sensitivity
      analysis showed that the probability of developing metastases under AS and
      utility weights under AS are a major sources of uncertainty. A Monte Carlo
      simulation revealed that AS was more likely to be cost-effective even under very
      high willingness to pay thresholds. CONCLUSION: AS is likely to be a cost-saving
      treatment strategy for some patients with early stage localised prostate cancer.
      However, cost-effectiveness is dependent on patients' valuation of health states.
      Better predictability of tumour progression and modified reimbursement practice
      would support widespread use of AS in the context of the German health care
      system. More research is necessary in order to reliably quantify the health
      benefits compared with initial treatment and account for patient preferences.

PMID- 24721558
TI  - Multicriteria decision analysis methods with 1000Minds for developing systemic
      sclerosis classification criteria.
AB  - OBJECTIVES: Classification criteria for systemic sclerosis (SSc) are being
      developed. The objectives were to develop an instrument for collating case data
      and evaluate its sensibility; use forced-choice methods to reduce and weight
      criteria; and explore agreement among experts on the probability that cases were
      classified as SSc. STUDY DESIGN AND SETTING: A standardized instrument was tested
      for sensibility. The instrument was applied to 20 cases covering a range of
      probabilities that each had SSc. Experts rank ordered cases from highest to
      lowest probability; reduced and weighted the criteria using forced-choice
      methods; and reranked the cases. Consistency in rankings was evaluated using
      intraclass correlation coefficients (ICCs). RESULTS: Experts endorsed clarity
      (83%), comprehensibility (100%), face and content validity (100%). Criteria were
      weighted (points): finger skin thickening (14-22), fingertip lesions (9-21),
      friction rubs (21), finger flexion contractures (16), pulmonary fibrosis (14),
      SSc-related antibodies (15), Raynaud phenomenon (13), calcinosis (12), pulmonary
      hypertension (11), renal crisis (11), telangiectasia (10), abnormal nailfold
      capillaries (10), esophageal dilation (7), and puffy fingers (5). The ICC across
      experts was 0.73 [95% confidence interval (CI): 0.58, 0.86] and improved to 0.80
      (95% CI: 0.68, 0.90). CONCLUSIONS: Using a sensible instrument and forced-choice
      methods, the number of criteria were reduced by 39% (range, 23-14) and weighted.
      Our methods reflect the rigors of measurement science and serve as a template for
      developing classification criteria.

PMID- 24721559
TI  - Influence of temporomandibular disorder on temporal and masseter muscles and
      occlusal contacts in adolescents: an electromyographic study.
AB  - BACKGROUND: The aim of the present study was to analyse the influence of
      temporomandibular disorder (TMD) on electromyographic activity in the masseter
      and temporal muscles of adolescents and investigate a possible association with
      the number of occlusal contacts. METHODS: The Helkimo Index was administered for
      the diagnosis of TMD and classification of the adolescents into three groups:
      without TMD; with mild TMD; and with moderate/severe TMD. Carbon paper was used
      for the determination of occlusal contact points. A standardised
      electromyographic evaluation was performed on the masticatory muscles at rest,
      during habitual chewing and during maximum voluntary clenching. The readings were
      normalised to maximum voluntary clenching. Statistical analysis involved the chi
      squared test and Fisher's exact test. The Kruskal-Wallis test and one-way
      analysis of variance with Dunn's post hoc test were used to compare differences
      between groups. Pearson's correlation coefficients (r) were calculated for the
      determination of correlations between the number of occlusal contacts and RMS
      values. RESULTS: Electromyography revealed significant differences in the right
      and left masseter and temporal muscles at rest and during chewing among the three
      groups. These differences were not observed during maximum voluntary clenching.
      No statistically significant differences were found between the groups with and
      without TMD regarding the number of occlusal contacts. CONCLUSION:
      Electromyographic activity in the masseter and temporal muscles was greater among
      adolescents with moderate to severe TMD.

PMID- 24721560
TI  - Evidence based palaeopathology: meta-analysis of Pubmed-listed scientific studies
      on pre-Columbian, South American mummies.
AB  - The aim of this study was to review all Pubmed((r))-listed palaeopathological
      studies performed on pre-Columbian South American mummies. A total of 61 studies
      were found (1977-2005). Review criteria included e.g. method of examination,
      method of mummification, palaeopathological diagnoses and individual age of
      mummies as well as dating, which ranged from 7500 to 500 years BP, mainly (if
      reported) originating from the Chiribaya and Chinchorro cultures. The average age
      of the 99 individually reported mummies was about 25 years. Only six studies
      included computed tomography, thirteen studies used classical radiography as an
      examination method. Three studies analysed parasite related diseases, especially
      caused by Trypanosoma cruzi. Among all of the reported infectious diseases (n=9),
      there were seven studies presenting cases of tuberculosis. The results were also
      compared inter-culturally. In 61 studies (37 epidemiological and 24 case reports)
      more than 6400 mummified individuals were analysed. By contrast, meta-analytic
      data for ancient Egyptian mummies (Zweifel et al., 2009) included about 3000
      analysed individuals in 131 studies (85 case reports and 46 epidemiological
      studies). In general, ancient Egyptian mummies were shown to be intentionally
      mummified, whereas the Pre-Columbian American mummies showed a great diversity of
      spontaneous mummification. However, ritualistic mummification methods were also
      practised (n=2). This study's results shall assist to improve evidence-based
      research in palaeopathology. 

PMID- 24721561
TI  - Surnames, geographic altitude, and digital dermatoglyphics in a male population
      from the province of Jujuy (Argentina).
AB  - The possible association between finger dermatoglyphic patterns and altitude and
      surname distribution was analyzed in a sample of adult males from the province of
      Jujuy, Argentina. We also investigated the biological affinity of this population
      with other South American natives and admixed populations. Fingerprints were
      obtained from 996 healthy men, aged 18-20 years, from the highlands (HL: 2500m,
      Puna and Quebrada) and lowlands (LL: Valle and Selvas). Surnames were classified
      into native/autochthonous (A) or foreign (F), resulting in three surname classes:
      FF, when both paternal and maternal surnames were of foreign origin; FA, when one
      surname was foreign and the other was native; and AA, when both surnames were
      native. Frequencies of finger dermatoglyphic patterns - arches (A), radial loops
      (RL), ulnar loops (UL), and whorls (W) - were determined for each digit in
      relation to geographic location, altitude, and surname origin, resulting in the
      following categories: HL-FF, HL-FA, HL-AA, LL-FF, LL-FA, and LL-AA. The
      statistical analyses showed that UL and RL were more common in individuals of HL
      origin, whereas W and A were more frequent in the LL males (p<0.05). Significant
      associations were observed between finger dermatoglyphic patterns and surname
      origin when geographic altitude was considered. In the HL group, UL was
      associated with AA and FA; in the LL group, the presence of A was associated with
      FF and FA. The distribution of dermatoglyphic patterns shows that the population
      of Jujuy belongs to the Andean gene pool and that it has undergone differential
      levels of admixture related to altitude. 

PMID- 24721562
TI  - Improvement of stability and enzymatic activity by site-directed mutagenesis of
      E. coli asparaginase II.
AB  - Bacterial asparaginases (EC 3.5.1.1) have attracted considerable attention
      because enzymes of this group are used in the therapy of certain forms of
      leukemia. Class II asparaginase from Escherichia coli (EcA), a homotetramer with
      a mass of 138 kDa, is especially effective in cancer therapy. However, the
      therapeutic potential of EcA is impaired by the limited stability of the enzyme
      in vivo and by the induction of antibodies in the patients. In an attempt to
      modify the properties of EcA, several variants with amino acid replacements at
      subunit interfaces were constructed and characterized. Chemical and thermal
      denaturation analysis monitored by activity, fluorescence, circular dichroism,
      and differential scanning calorimetry showed that certain variants with exchanges
      that weaken dimer-dimer interactions exhibited complex denaturation profiles with
      active dimeric and/or inactive monomeric intermediates appearing at low
      denaturant concentrations. By contrast, other EcA variants showed considerably
      enhanced activity and stability as compared to the wild-type enzyme. Thus, even
      small changes at a subunit interface may markedly affect EcA stability without
      impairing its catalytic properties. Variants of this type may have a potential
      for use in the asparaginase therapy of leukemia.

PMID- 24721563
TI  - Probing the catalytic mechanism of bovine CD38/NAD+ glycohydrolase by site
      directed mutagenesis of key active site residues.
AB  - Bovine CD38/NAD(+) glycohydrolase catalyzes the hydrolysis of NAD(+) to
      nicotinamide and ADP-ribose and the formation of cyclic ADP-ribose via a stepwise
      reaction mechanism. Our recent crystallographic study of its Michaelis complex
      and covalently-trapped intermediates provided insights into the modalities of
      substrate binding and the molecular mechanism of bCD38. The aim of the present
      work was to determine the precise role of key conserved active site residues
      (Trp118, Glu138, Asp147, Trp181 and Glu218) by focusing mainly on the cleavage of
      the nicotinamide-ribosyl bond. We analyzed the kinetic parameters of mutants of
      these residues which reside within the bCD38 subdomain in the vicinity of the
      scissile bond of bound NAD(+). To address the reaction mechanism we also
      performed chemical rescue experiments with neutral (methanol) and ionic (azide,
      formate) nucleophiles. The crucial role of Glu218, which orients the substrate
      for cleavage by interacting with the N-ribosyl 2'-OH group of NAD(+), was
      highlighted. This contribution to catalysis accounts for almost half of the
      reaction energy barrier. Other contributions can be ascribed notably to Glu138
      and Asp147 via ground-state destabilization and desolvation in the vicinity of
      the scissile bond. Key interactions with Trp118 and Trp181 were also proven to
      stabilize the ribooxocarbenium ion-like transition state. Altogether we propose
      that, as an alternative to a covalent acylal reaction intermediate with Glu218,
      catalysis by bCD38 proceeds through the formation of a discrete and transient
      ribooxocarbenium intermediate which is stabilized within the active site mostly
      by electrostatic interactions. 

PMID- 24721564
TI  - Iatrogenic uterine perforation and bowel penetration using a Hohlmanipulator: A
      case report.
AB  - INTRODUCTION: Adequate exposure is a vital factor in total laparoscopic
      hysterectomy, and uterine manipulators have been used in achieving that. The Hohl
      uterine manipulator has been considered to be one of the safer manipulators.
      Beside adequate exposure, it is associated with lower intraoperative
      complications. However, we report a case of iatrogenic uterine rupture with the
      Hohl manipulator which also caused bowel penetration. PRESENTATION OF CASE: A 52
      year-old woman with endometrial hyperplasia was scheduled for total laparoscopic
      hysterectomy. Prior to entering into the abdomen, the Hohl uterine manipulator
      was introduced into the uterine cavity without force. During the laparoscopic
      exploration, we noted that the tip of the Hohl manipulator had perforated the
      posterior uterine fundus and penetrated the bowel. Therefore, laparotomy was
      performed, and the bowel injury was repaired by a colorectal surgeon. DISCUSSION:
      The Hohl uterine manipulator is safe and easy to use, and is associated with
      decreased intraoperative injuries. However, the complications observed due to the
      improper use of an uterine manipulator can overshadow any advantages of
      manipulator. In the present report, we describe a case of uterine perforation and
      bowel penetration caused by the Hohl uterine manipulator during total
      laparoscopic hysterectomy, which required conversion to laparotomy. The cause for
      this complication is associated with improper usage of the uterine manipulator.
      CONCLUSION: Uterine manipulator may cause uterine perforation and bowel
      penetration at the beginning of the hysterectomy procedure. These types of
      complications can be prevented by proper application of the Hohl manipulator into
      the uterus under direct pelvic visualization.

PMID- 24721565
TI  - Shigella stands up to the challenge of adhesion.
AB  - The invasion process of S. flexneri is well characterized, but mechanisms
      underlying this bacterium's adhesion to host cells have remained obscure. In this
      issue of Cell Host & Microbe, Brotcke Zumsteg et al. (2014) report a surprising
      role for the Shigella virulence factor IcsA (VirG) as an adhesin. 

PMID- 24721566
TI  - A host MicroRNA brokers truce with HSV-1.
AB  - Establishing lifelong infection and periodically shedding infectious progeny is a
      successful strategy employed by several persistent pathogens. In this issue of
      Cell Host & Microbe, Pan et al. (2014) demonstrate that a cell-type-specific host
      microRNA can restrict gene expression and pathogenicity of herpes simplex virus
      1, thereby promoting long-term infection. 

PMID- 24721567
TI  - When PRRs collide: mincle meddles with dectin and toll.
AB  - Pattern recognition receptors (PRR) promote pathogen eradication and shape
      adaptive immunity. Although evidence suggests PRRs can antagonize each other, few
      detailed mechanisms are known. Wevers et al. (2014) uncover a mechanism of PRR
      antagonism where fungal-induced Mincle signaling suppresses IL-12 transcription
      induced by other PRRs and thereby abates antifungal immunity. 

PMID- 24721568
TI  - At the intersection of plant growth and immunity.
AB  - The tradeoff between growth and immunity is regulated by integrating hormonal
      cues, biotic signals, and developmental programs, and is fine-tuned to maximize
      organismal growth and survival. Four recent papers, including Chandran et al.
      (2014) in this issue of Cell Host & Microbe, provide insights into the underlying
      mechanisms in plants. 

PMID- 24721569
TI  - Self and nonself: how autophagy targets mitochondria and bacteria.
AB  - Autophagy is an evolutionarily conserved pathway that transports cytoplasmic
      components for degradation into lysosomes. Selective autophagy can capture
      physically large objects, including cell-invading pathogens and damaged or
      superfluous organelles. Selectivity is achieved by cargo receptors that detect
      substrate-associated "eat-me" signals. In this Review, we discuss basic
      principles of selective autophagy and compare the "eat-me" signals and cargo
      receptors that mediate autophagy of bacteria and bacteria-derived endosymbionts
      i.e., mitochondria. 

PMID- 24721570
TI  - Plasmacytoid dendritic cells mediate anti-inflammatory responses to a gut
      commensal molecule via both innate and adaptive mechanisms.
AB  - Polysaccharide A (PSA), the archetypical immunomodulatory molecule of the gut
      commensal Bacteroides fragilis, induces regulatory T cells to secrete the anti
      inflammatory cytokine interleukin-10 (IL-10). The cellular mediators of PSA's
      immunomodulatory properties are incompletely understood. In a mouse model of
      colitis, we find that PSA requires both innate and adaptive immune mechanisms to
      generate protection. Plasmacytoid DCs (PDCs) exposed to PSA do not produce
      proinflammatory cytokines, but instead they specifically stimulate IL-10
      secretion by CD4+ T cells and efficiently mediate PSA-afforded immunoprotection.
      PSA induces and preferentially ligates Toll-like receptor 2 on PDCs but not on
      conventional DCs. Compared with other TLR2 ligands, PSA is better at enhancing
      PDC expression of costimulatory molecules required for protection against
      colitis. PDCs can thus orchestrate the beneficial immunoregulatory interaction of
      commensal microbial molecules, such as PSA, through both innate and adaptive
      immune mechanisms. 

PMID- 24721571
TI  - The Pla protease of Yersinia pestis degrades fas ligand to manipulate host cell
      death and inflammation.
AB  - Pneumonic plague is a deadly respiratory disease caused by Yersinia pestis. The
      bacterial protease Pla contributes to disease progression and manipulation of
      host immunity, but the mechanisms by which this occurs are largely unknown. Here
      we show that Pla degrades the apoptotic signaling molecule Fas ligand (FasL) to
      prevent host cell apoptosis and inflammation. Wild-type Y. pestis, but not a Pla
      mutant (Deltapla), degrades FasL, which results in decreased downstream caspase
      3/7 activation and reduced apoptosis. Similarly, lungs of mice challenged with
      wild-type Y. pestis show reduced levels of FasL and activated caspase-3/7
      compared to Deltapla infection. Consistent with a role for FasL in regulating
      immune responses, Deltapla infection results in aberrant proinflammatory cytokine
      levels. The loss of FasL or inhibition of caspase activity alters host
      inflammatory responses and enables enhanced Y. pestis outgrowth in the lungs.
      Thus, by degrading FasL, Y. pestis manipulates host cell death pathways to
      facilitate infection. 

PMID- 24721572
TI  - IcsA is a Shigella flexneri adhesin regulated by the type III secretion system
      and required for pathogenesis.
AB  - Following contact with the epithelium, the enteric intracellular bacterial
      pathogen Shigella flexneri invades epithelial cells and escapes intracellular
      phagosomal destruction using its type III secretion system (T3SS). The bacterium
      replicates within the host cell cytosol and spreads between cells using actin
      based motility, which is mediated by the virulence factor IcsA (VirG). Whereas S.
      flexneri invasion is well characterized, adhesion mechanisms of the bacterium
      remain elusive. We found that IcsA also functions as an adhesin that is both
      necessary and sufficient to promote contact with host cells. As adhesion can be
      beneficial or deleterious depending on the host cell type, S. flexneri regulates
      IcsA-dependent adhesion. Activation of the T3SS in response to the bile salt
      deoxycholate triggers IcsA-dependent adhesion and enhances pathogen invasion.
      IcsA-dependent adhesion contributes to virulence in a mouse model of shigellosis,
      underscoring the importance of this adhesin to S. flexneri pathogenesis. 

PMID- 24721574
TI  - A murid gamma-herpesviruses exploits normal splenic immune communication routes
      for systemic spread.
AB  - Gamma-herpesviruses (gammaHVs) are widespread oncogenic pathogens that
      chronically infect circulating lymphocytes. How they subvert the immune check
      point function of the spleen to promote persistent infection is not clear. We
      show that Murid Herpesvirus-4 (MuHV-4) enters the spleen by infecting marginal
      zone (MZ) macrophages, which provided a conduit to MZ B cells. Relocation of MZ B
      cells to the white pulp allowed virus transfer to follicular dendritic cells.
      From here the virus reached germinal center B cells to establish persistent
      infection. Mice lacking MZ B cells, or treated with a sphingosine-1-phosphate
      receptor agonist to dislocate them, were protected against MuHV-4 colonization.
      MuHV-4 lacking ORF27, which encodes a glycoprotein necessary for efficient
      intercellular spread, could infect MZ macrophages but was impaired in long-term
      infection. Thus, MuHV-4, a gammaHV, exploits normal immune communication routes
      to spread by serial lymphoid/myeloid exchange. 

PMID- 24721573
TI  - A neuron-specific host microRNA targets herpes simplex virus-1 ICP0 expression
      and promotes latency.
AB  - After infecting peripheral sites, herpes simplex virus (HSV) invades the nervous
      system and initiates latent infection in sensory neurons. Establishment and
      maintenance of HSV latency require host survival, and entail repression of
      productive cycle ("lytic") viral gene expression. We find that a neuron-specific
      microRNA, miR-138, represses expression of ICP0, a viral transactivator of lytic
      gene expression. A mutant HSV-1 (M138) with disrupted miR-138 target sites in
      ICP0 mRNA exhibits enhanced expression of ICP0 and other lytic proteins in
      infected neuronal cells in culture. Following corneal inoculation, M138-infected
      mice have higher levels of ICP0 and lytic transcripts in trigeminal ganglia
      during establishment of latency, and exhibit increased mortality and encephalitis
      symptoms. After full establishment of latency, the fraction of trigeminal ganglia
      harboring detectable lytic transcripts is greater in M138-infected mice. Thus,
      miR-138 is a neuronal factor that represses HSV-1 lytic gene expression,
      promoting host survival and viral latency. 

PMID- 24721575
TI  - Neutrophils recruited by IL-22 in peripheral tissues function as TRAIL-dependent
      antiviral effectors against MCMV.
AB  - During primary infection, murine cytomegalovirus (MCMV) spreads systemically,
      resulting in virus replication and pathology in multiple organs. This
      disseminated infection is ultimately controlled, but the underlying immune
      defense mechanisms are unclear. Investigating the role of the cytokine IL-22 in
      MCMV infection, we discovered an unanticipated function for neutrophils as potent
      antiviral effector cells that restrict viral replication and associated
      pathogenesis in peripheral organs. NK-, NKT-, and T cell-secreted IL-22
      orchestrated antiviral neutrophil-mediated responses via induction in stromal
      nonhematopoietic tissue of the neutrophil-recruiting chemokine CXCL1. The
      antiviral effector properties of infiltrating neutrophils were directly linked to
      the expression of TNF-related apoptosis-inducing ligand (TRAIL). Our data
      identify a role for neutrophils in antiviral defense, and establish a functional
      link between IL-22 and the control of antiviral neutrophil responses that
      prevents pathogenic herpesvirus infection in peripheral organs. 

PMID- 24721576
TI  - Cellular DDX21 RNA helicase inhibits influenza A virus replication but is
      counteracted by the viral NS1 protein.
AB  - Influenza A virus RNA synthesis is catalyzed by the viral polymerase comprised of
      the PA, PB1, and PB2 proteins. We show that the host DDX21 RNA helicase restricts
      influenza A virus by binding PB1 and inhibiting polymerase assembly, resulting in
      reduced viral RNA and protein synthesis. Later during infection, the viral NS1
      protein overcomes this restriction by binding to DDX21 and displacing PB1. DDX21
      binds to a region of the NS1 N-terminal domain that also participates in other
      critical functions. A virus mutant whose NS1 protein is unable to bind DDX21
      exhibits reduced viral protein synthesis at both late and early times of
      infection, a phenotype converted to wild-type upon DDX21 knockdown. As sequential
      interaction of PB1 and NS1 with DDX21 leads to temporal regulation of viral gene
      expression, influenza A virus likely uses the DDX21-NS1 interaction not only to
      overcome restriction, but also to regulate the viral life cycle. 

PMID- 24721577
TI  - Fungal engagement of the C-type lectin mincle suppresses dectin-1-induced
      antifungal immunity.
AB  - Recognition of fungal pathogens by C-type lectin receptor (CLR) dectin-1 on human
      dendritic cells is essential for triggering protective antifungal TH1 and TH17
      immune responses. We show that Fonsecaea monophora, a causative agent of
      chromoblastomycosis, a chronic fungal skin infection, evades these antifungal
      responses by engaging CLR mincle and suppressing IL-12, which drives TH1
      differentiation. Dectin-1 triggering by F. monophora activates transcription
      factor IRF1, which is crucial for IL12A transcription via nucleosome remodeling.
      However, simultaneous F. monophora binding to mincle induces an E3 ubiquitin
      ligase Mdm2-dependent degradation pathway, via Syk-CARD9-mediated PKB signaling,
      that leads to loss of nuclear IRF1 activity, hence blocking IL12A transcription.
      The absence of IL-12 leads to impaired TH1 responses and promotes TH2
      polarization. Notably, mincle is similarly exploited by other chromoblastomycosis
      associated fungi to redirect TH responses. Thus, mincle is a fungal receptor that
      can suppress antifungal immunity and, as such, is a potential therapeutic target.

PMID- 24721578
TI  - Atypical E2F transcriptional repressor DEL1 acts at the intersection of plant
      growth and immunity by controlling the hormone salicylic acid.
AB  - In plants, the activation of immunity is often inversely correlated with growth.
      Mechanisms that control plant growth in the context of pathogen challenge and
      immunity are unclear. Investigating Arabidopsis infection with the powdery mildew
      fungus, we find that the Arabidopsis atypical E2F DEL1, a transcriptional
      repressor known to promote cell proliferation, represses accumulation of the
      hormone salicylic acid (SA), an established regulator of plant immunity. DEL1
      deficient plants are more resistant to pathogens and slightly smaller than wild
      type. The resistance and size phenotypes of DEL1-deficient plants are due to the
      induction of SA and activation of immunity in the absence of pathogen challenge.
      Moreover, Enhanced Disease Susceptibility 5 (EDS5), a SA transporter required for
      elevated SA and immunity, is a direct repressed target of DEL1. Together, these
      findings indicate that DEL1 control of SA levels contributes to regulating the
      balance between growth and immunity in developing leaves. 

PMID- 24721579
TI  - Using random forest to classify linear B-cell epitopes based on amino acid
      properties and molecular features.
AB  - Identification and characterization of B-cell epitopes in target antigens was one
      of the key steps in epitopes-driven vaccine design, immunodiagnostic tests, and
      antibody production. Experimental determination of epitopes was labor-intensive
      and expensive. Therefore, there was an urgent need of computational methods for
      reliable identification of B-cell epitopes. In current study, we proposed a novel
      peptide feature description method which combined peptide amino acid properties
      with chemical molecular features. Based on these combined features, a random
      forest (RF) classifier was adopted to classify B-cell epitopes and non-epitopes.
      RF is an ensemble method that uses recursive partitioning to generate many trees
      for aggregating the results; and it always produces highly competitive models.
      The classification accuracy, sensitivity, specificity, Matthews correlation
      coefficient (MCC), and area under the curve (AUC) values for current method were
      78.31%, 80.05%, 72.23%, 0.5836, and 0.8800, respectively. These results showed
      that an appropriate combination of peptide amino acid features and chemical
      molecular features with a RF model could enhance the prediction performance of
      linear B-cell epitopes. Finally, a freely online service was available at
      http://sysbio.yznu.cn/Research/Epitopesprediction.aspx.

PMID- 24721580
TI  - Antioxidant and antitumor activities of 4-arylcoumarins and 4-aryl-3,4
      dihydrocoumarins.
AB  - Five 4-arylcoumarins (1c-g) and twelve 3,4-dihydro-4-arylcoumarins (2a-l) were
      synthesized and tested for antioxidant activity, antitumor activity, toxicity and
      structure-activity relationships analysis. 4-Arylcoumarins and 3,4-dihydro-4
      arylcoumarins that possess two hydroxyl groups in ortho position, such as 1d, 1f,
      2a, 2f, 2g and 2h had stronger radical scavenging properties than that of vitamin
      C (Vit C) in ABTS(+) assay. Kinetic traces of scavenging ABTS(+) and DPPH
      radicals showed that all the reaction could reached endpoint in 1 min, which was
      similar with Vit C. 4-Arylcoumarins with 3'-hydroxyl-4'-methylphenyl structural
      show more efficient NO radical scavenging activity. Three compounds 2e, 1f and
      2a, in particular had superior EC50 for NO scavenging than did Vit C. MTT assay
      indicated that one compound in particular had a potential antitumor effect,
      inhibiting proliferation of BGC-823 cells and almost completely killing them at a
      concentration 62.5 mg/L. With same concentration 100 MUg/mL, hemolytic analysis
      in rabbit red blood cells showed that only two compounds had hemolytic activity
      with a little more than 5% hemolysis. Injection and oral toxicity tests on
      Galleria mellonella larvae showed that none of the tested 4-arylcoumarins
      significantly affected their appetite, viability and mortality. 

PMID- 24721581
TI  - Characterization of hyaluronic acid specific hyaluronate lyase (HylP) from
      Streptococcus pyogenes.
AB  - Streptococcus pyogenes is associated with a wide variety of mucosal and invasive
      infections that claim human life. The conversion from non pathogenic to toxigenic
      strain of S. pyogenes are thought to be mediated by bacteriophage infection in
      several cases. The hyaluronic acid (HA) degrading enzyme Hyaluronate lyase (HL)
      is proposed to be one of the key bacteriophage-encoded virulence factors. In the
      present work, HL of S. pyogenes bacteriophage H4489A (HylP) was expressed in
      Escherichia coli, purified and their structural and functional properties were
      studied. The enzyme exists in an extended trimeric conformation whose function is
      influenced by calcium ions. The collagenous Gly-X-Y motif of the enzyme
      influences stability and interact with calcium ions suggesting its role in the
      enzyme regulation The HylP shows sequential unfolding through the N-terminal
      domain. The primary catalytic residues of the enzyme seem to be in the first
      pocket consisting of Asp170 and Tyr182; however the enzyme activity is
      considerably reduced with mutation in the second pocket consisting of Glu295 and
      Tyr298. The catalytic residues span between the regions containing 135-308 amino
      acids where both the catalytic pocket has a prominent positively charged residue.
      The net positive potential of the cleft may help in recruiting the negatively
      charged polymeric HA. Interestingly, unlike other phage HLs, HylP is inhibited by
      l-ascorbic through non competitive manner.

PMID- 24721582
TI  - pH-dependent relationship between thermodynamic and kinetic stability in the
      denaturation of human phosphoglycerate kinase 1.
AB  - Human phosphoglycerate kinase 1 (hPGK1) is a glycolytic enzyme essential for ATP
      synthesis, and it is implicated in different pathological conditions such as
      inherited diseases, oncogenesis and activation of drugs for cancer and viral
      treatments. Particularly, mutations in hPGK1 cause human PGK1 deficiency, a rate
      metabolic conformational disease. We have recently found that most of these
      mutations cause protein kinetic destabilization by significant changes in the
      structure/energetics of the transition state for irreversible denaturation. In
      this work, we explore the relationships between protein conformation,
      thermodynamic and kinetic stability in hPGK1 by performing comprehensive analyses
      in a wide pH range (2.5-8). hPGK1 remains in a native conformation at pH 5-8, but
      undergoes a conformational transition to a molten globule-like state at acidic
      pH. Interestingly, hPGK1 kinetic stability remains essentially constant at pH 6
      8, but is significantly reduced when pH is decreased from 6 to 5. We found that
      this decrease in kinetic stability is caused by significant changes in the
      energetic/structural balance of the denaturation transition state, which diverge
      from those found for disease-causing mutations. We also show that protein kinetic
      destabilization by acidic pH is strongly linked to lower thermodynamic stability,
      while in disease-causing mutations seems to be linked to lower unfolding
      cooperativity. These results highlight the plasticity of the hPGK1 denaturation
      mechanism that responds differently to changes in pH and in disease-causing
      mutations. New insight is presented into the different factors contributing to
      hPGK1 thermodynamic and kinetic stability and the role of denaturation mechanisms
      in hPGK1 deficiency. 

PMID- 24721583
TI  - Dermatofibrosarcoma protuberans mimicking cutaneous sarcoidosis in a patient with
      lung sarcoidosis.

PMID- 24721584
TI  - Off-hour presentation and outcomes in patients with acute ischemic stroke: a
      systematic review and meta-analysis.
AB  - BACKGROUND: Studies have suggested that patients with acute ischemic stroke who
      present to the hospital during off-hours (weekends and nights) may or may not
      have worse clinical outcomes compared to patients who present during regular
      hours. METHODS: We searched Medline In-Process & Other Non-Indexed Citations,
      MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, and Scopus through
      August 2013, and included any study that evaluated the association between time
      of patient presentation to a healthcare facility and mortality or modified Rankin
      Scale in acute ischemic stroke. Quality of studies was assessed with the
      Newcastle-Ottawa Scale. A random-effect meta-analysis model was applied.
      Heterogeneity was assessed using the Q statistic and I(2). A priori subgroup
      analyses were used to explain observed heterogeneity. RESULTS: A total of 21
      cohort studies (23 cohorts) with fair quality enrolling 1,421,914 patients were
      included. Off-hour presentation for patients with acute ischemic stroke was
      associated with significantly higher short-term mortality (OR, 1.11, 95% CI 1.06
      1.17). Presenting at accredited stroke centers (OR 1.04, 95% CI 0.98-1.11) and
      countries in North America (OR 1.05, 95% CI 1.01-1.09) were associated with
      smaller increase in mortality during off-hours. The results were not
      significantly different between adjusted (OR, 1.11, 95% CI 1.05-1.16) and
      unadjusted (OR, 1.13, 95% CI 0.95-1.35) outcomes. The proportion of patients with
      modified Rankin Scale at discharge >= 2-3 was higher in patients presenting
      during off-hours (OR, 1.14, 95% CI 1.06-1.22). DISCUSSION: The evidence suggests
      that patients with acute ischemic stroke presenting during off-hours have higher
      short-term mortality and greater disability at discharge.

PMID- 24721585
TI  - Transcatheter aortic valve implantation of the direct flow medical aortic valve
      with minimal or no contrast.
AB  - The 18F Direct Flow Medical (DFM) THV has conformable sealing rings, which
      minimizes aortic regurgitation and permits full hemodynamic assessment of valve
      performance prior to permanent implantation. During the DISCOVER trial, three
      patients who were at risk for receiving contrast media, two due to severe CKD and
      one due to a recent hyperthyroid reaction to contrast, underwent DFM implantation
      under fluoroscopic and transesophageal guidance without aortography during either
      positioning or to confirm the final position. Valve positioning was based on the
      optimal angiographic projection as calculated by the pre-procedural multislice CT
      scan. Precise optimization of valve position was performed to minimize transvalve
      gradient and aortic regurgitation. Prior to final implantation, transvalve
      hemodynamics were assessed invasively and by TEE. The post-procedure mean
      gradients were 7, 10, 11mm Hg. The final AVA by echo was 1.70, 1.40 and
      1.68cm(2). Total aortic regurgitation post-procedure was none or trace in all
      three patients. Total positioning and assessment of valve performance time was 4,
      6, and 12minutes. Contrast was only used to confirm successful percutaneous
      closure of the femoral access site. The total contrast dose was 5, 8, 12cc.
      Baseline eGFR and creatinine was 28, 22, 74mL/min/1.73m(2) and 2.35, 2.98, and
      1.03mg/dL, respectively. Renal function was unchanged post-procedure: eGFR=25,
      35, and 96mL/min/1.73m(2) and creatinine=2.58, 1.99, and 1.03mg/dL, respectively.
      In conclusion, the DFM THV provides the ability to perform TAVI with minimal or
      no contrast. The precise and predictable implantation technique can be performed
      with fluoro and echo guidance.

PMID- 24721586
TI  - TED-Time and life saving External Defibrillator for home-use.
AB  - Sudden Cardiac Death--SCD --is a major unmet health problem that needs urgent and
      prompt solution. AICDs are very expensive, risky and indicated for a small group
      of patients, at the highest risk. AEDs--Automatic External Defibrillators--are
      designed for public places and although safe, cannot enter the home-market due to
      their cost and need for constant, high-cost maintenance. We developed TED, a low
      cost AED that derives its energy off the mains, designed for home-use, to save
      SCD victims' lives.

PMID- 24721587
TI  - Lack of effect of colesevelam HCl on the single-dose pharmacokinetics of aspirin,
      atenolol, enalapril, phenytoin, rosiglitazone, and sitagliptin.
AB  - AIMS: Drug interactions with bile acid sequestrants are primarily due to the
      potential of these agents to bind to concomitant drugs. Six clinical studies were
      performed to determine the effects of colesevelam on the pharmacokinetics of
      aspirin, atenolol, enalapril, phenytoin, rosiglitazone, and sitagliptin. METHODS:
      All six studies enrolled healthy subjects aged 18-45 years. The phenytoin study
      used a single-dose, three-period crossover design (phenytoin alone, phenytoin
      simultaneously with colesevelam, and phenytoin 4h before colesevelam). The other
      studies used a two-period crossover design (test drug alone and test drug
      simultaneously with colesevelam). Colesevelam (3750mg once daily) was dosed
      throughout the pharmacokinetic sampling period. After each single dose of the
      test drug, serial blood samples were collected for determination of plasma drug
      concentrations and calculation of pharmacokinetic parameters. RESULTS: For all
      six test drugs, 90% CIs for geometric least-squares mean ratios of AUC and Cmax
      for the measured analytes were within specified limits, indicating no interaction
      between the test drug and colesevelam. CONCLUSIONS: Aspirin, atenolol, enalapril,
      rosiglitazone, and sitagliptin may be taken with colesevelam. Although the
      phenytoin study indicated no pharmacokinetic interaction, phenytoin should
      continue to be taken >=4h before colesevelam in accordance with current
      prescribing information.

PMID- 24721588
TI  - Iodine 125 brachytherapy with vitrectomy and silicone oil in the treatment of
      uveal melanoma: 1-to-1 matched case-control series.
AB  - PURPOSE: We initially reported the radiation-attenuating effect of silicone oil
      1000 centistokes for iodine 125. The purpose of this report was to compare the
      clinical outcomes in case patients who had iodine 125 brachytherapy with
      vitrectomy and silicone oil 1000 centistokes with the outcomes in matched control
      patients who underwent brachytherapy alone. METHODS AND MATERIALS: Consecutive
      patients with uveal melanoma who were treated with iodine 125 plaque
      brachytherapy and vitrectomy with silicone oil with minimum 1-year follow-up were
      included. Control patients who underwent brachytherapy alone were matched for
      tumor size, location, and sex. Baseline patient and tumor characteristics and
      tumor response to radiation, final visual acuity, macular status, central macular
      thickness by ocular coherence tomography (OCT), cataract progression, and
      metastasis at last follow-up visit were compared. Surgical complications were
      also determined. RESULTS: Twenty case patients met the inclusion criteria. The
      average follow-up time was 22.1 months in case patients and 19.4 months in
      control patients. The final logMAR vision was 0.81 in case patients and 1.1 in
      control patients (P=.071); 8 case patients and 16 control patients had abnormal
      macular findings (P=.011); and the average central macular thickness by OCT was
      293.2 MUm in case patients and 408.5 MUm in control patients (P=.016). Eleven
      case patients (55%) and 1 control patient (5%) had required cataract surgery at
      last follow-up (P=.002). Four patients in the case group and 1 patient in the
      control group experienced metastasis (P=.18). Among the cases, intraoperative
      retinal tear occurred in 3 patients; total serous retinal detachment and macular
      hole developed in 1 case patient each. There was no case of rhegmatogenous
      retinal detachment, treatment failure, or local tumor dissemination in case
      patients or control patients. CONCLUSIONS: With up to 3 years of clinical follow
      up, silicone oil during brachytherapy for the treatment of uveal melanoma
      resulted in fewer abnormal maculas, lower central macular thickness on OCT, and a
      trend toward better final visual acuity in comparison with matched control
      patients who underwent brachytherapy alone.

PMID- 24721589
TI  - Posttraumatic stress disorder after high-dose-rate brachytherapy for cervical
      cancer with 2 fractions in 1 application under spinal/epidural anesthesia:
      incidence and risk factors.
AB  - PURPOSE: To investigate the psychological consequences of high-dose-rate
      brachytherapy with 2 fractions in 1 application under spinal/epidural anesthesia
      in the treatment of locally advanced cervical cancer. METHODS AND MATERIALS: In
      50 patients with locally advanced cervical cancer, validated questionnaires were
      used for prospective assessment of acute and posttraumatic stress disorder
      (ASD/PTSD) (Impact of Event Scale-Revision), anxiety/depression (Hospital Anxiety
      and Depression Scale), quality of life (European Organization for Research and
      Treatment of Cancer Quality of Life Questionnaire Core 30/Cervical Cancer 24),
      physical functioning (World Health Organization performance status), and pain
      (visual analogue scale), before and during treatment and 1 week and 3 months
      after treatment. Qualitative interviews were recorded in open format for content
      analysis. RESULTS: Symptoms of ASD occurred in 30% of patients 1 week after
      treatment; and of PTSD in 41% 3 months after treatment in association with this
      specific brachytherapy procedure. Pretreatment predictive variables explain 82%
      of the variance of PTSD symptoms. Helpful experiences were the support of the
      treatment team, psychological support, and a positive attitude. Stressful factors
      were pain, organizational problems during treatment, and immobility between
      brachytherapy fractions. CONCLUSIONS: The specific brachytherapy procedure, as
      performed in the investigated mono-institutional setting with 2 fractions in 1
      application under spinal/epidural anesthesia, bears a considerable risk of
      traumatization. The source of stress seems to be not the brachytherapy
      application itself but the maintenance of the applicator under epidural
      anesthesia in the time between fractions. Patients at risk may be identified
      before treatment, to offer targeted psycho-social support. The patients' open
      reports regarding helpful experiences are an encouraging feedback for the
      treatment team; the reported stressful factors serve as a basis for improvement
      of patient management, especially regarding pain control.

PMID- 24721590
TI  - Locoregional recurrence risk for patients with T1,2 breast cancer with 1-3
      positive lymph nodes treated with mastectomy and systemic treatment.
AB  - PURPOSE: Postmastectomy radiation therapy (PMRT) has been shown to benefit breast
      cancer patients with 1 to 3 positive lymph nodes, but it is unclear how modern
      changes in management have affected the benefits of PMRT. METHODS AND MATERIALS:
      We retrospectively analyzed the locoregional recurrence (LRR) rates in 1027
      patients with T1,2 breast cancer with 1 to 3 positive lymph nodes treated with
      mastectomy and adjuvant chemotherapy with or without PMRT during an early era
      (1978-1997) and a later era (2000-2007). These eras were selected because they
      represented periods before and after the routine use of sentinel lymph node
      surgery, taxane chemotherapy, and aromatase inhibitors. RESULTS: 19% of 505
      patients treated in the early era and 25% of the 522 patients in the later era
      received PMRT. Patients who received PMRT had significantly higher-risk disease
      features. PMRT reduced the rate of LRR in the early era cohort, with 5-year rates
      of 9.5% without PMRT and 3.4% with PMRT (log-rank P=.028) and 15-year rates 14.5%
      versus 6.1%, respectively; (Cox regression analysis: adjusted hazard ratio [AHR]
      0.37, P=.035). However, PMRT did not appear to benefit patients treated in the
      later cohort, with 5-year LRR rates of 2.8% without PMRT and 4.2% with PMRT
      (P=.48; Cox analysis: AHR 1.41, P=.48). The most significant factor predictive of
      LRR for the patients who did not receive PMRT was the era in which the patient
      was treated (AHR 0.35 for later era, P<.001). CONCLUSION: The risk of LRR for
      patients with T1,2 breast cancer with 1 to 3 positive lymph nodes treated with
      mastectomy and systemic treatment is highly dependent on the era of treatment.
      Modern treatment advances and the selected use of PMRT for those with high-risk
      features have allowed for identification of a cohort at very low risk for LRR
      without PMRT.

PMID- 24721591
TI  - Once-daily radiation therapy for inflammatory breast cancer.
AB  - PURPOSE: Inflammatory breast cancer (IBC) is a rare and aggressive breast cancer
      variant treated with multimodality therapy. A variety of approaches intended to
      escalate the intensity and efficacy of radiation therapy have been reported,
      including twice-daily radiation therapy, dose escalation, and aggressive use of
      bolus. Herein, we examine our outcomes for patients treated with once-daily
      radiation therapy with aggressive bolus utilization, focusing on treatment
      technique. METHODS AND MATERIALS: A retrospective review of patients with
      nonmetastatic IBC treated from January 1, 2000, through December 31, 2010, was
      performed. Locoregional control (LRC), disease-free survival (DFS), overall
      survival (OS) and predictors thereof were assessed. RESULTS: Fifty-two women with
      IBC were identified, 49 (94%) of whom were treated with neoadjuvant chemotherapy.
      All underwent mastectomy followed by adjuvant radiation therapy. Radiation was
      delivered in once-daily fractions of 1.8 to 2.25 Gy (median, 2 Gy). Patients were
      typically treated with daily 1-cm bolus throughout treatment, and 33 (63%)
      received a subsequent boost to the mastectomy scar. Five-year Kaplan Meier
      survival estimates for LRC, DFS, and OS were 81%, 56%, and 64%, respectively.
      Locoregional recurrence was associated with poorer OS (P<.001; hazard ratio [HR],
      4.1). Extracapsular extension was associated with worse LRC (P=.02), DFS
      (P=.007), and OS (P=.002). Age greater than 50 years was associated with better
      DFS (P=.03). Pathologic complete response was associated with a trend toward
      improved LRC (P=.06). CONCLUSIONS: Once-daily radiation therapy with aggressive
      use of bolus for IBC results in outcomes consistent with previous reports using
      various intensified radiation therapy regimens. LRC remains a challenge despite
      modern systemic therapy. Extracapsular extension, age <=50 years, and lack of
      complete response to chemotherapy appear to be associated with worse outcomes.
      Novel strategies are needed in IBC, particularly among these subsets of patients.

PMID- 24721593
TI  - Visible light catalysis of rhodamine B using nanostructured Fe(2)O(3), TiO(2) and
      TiO(2)/Fe(2)O(3) thin films.
AB  - The Fe(2)O(3), TiO(2) and TiO(2)/Fe(2)O(3) composite films are deposited using
      spray pyrolysis method onto glass and FTO coated substrates. The structural,
      morphological, optical and photocatalytic properties of Fe(2)O(3), TiO(2) and
      TiO(2)/Fe(2)O(3) thin films are studied. XRD analysis confirms that films are
      polycrystalline with rhombohedral and tetragonal crystal structures for Fe2O3 and
      TiO(2) respectively. The photocatalytic activity was tested for the degradation
      of Rhrodamine B (Rh B) in aqueous medium. The rate constant (-k) was evaluated as
      a function of the initial concentration of species. Substantial reduction in
      concentrations of organic species was observed from COD and TOC analysis.
      Photocatalytic degradation effect is relatively higher in case of the
      TiO(2)/Fe(2)O(3) than TiO(2) and Fe(2)O(3) thin film photoelectrodes in the
      degradation of Rh B and 98% removal efficiency of Rh B is obtained after 20min.
      The photocatalytic experimental results indicate that TiO(2)/alpha-Fe(2)O(3)
      photoelectrode is promising material for removing of water pollutants.

PMID- 24721592
TI  - Positron emission tomography/computed tomography findings during therapy predict
      outcome in patients with diffuse large B-cell lymphoma treated with chemotherapy
      alone but not in those who receive consolidation radiation.
AB  - PURPOSE: To assess the value of mid-therapy positron emission tomography (PET)
      findings for predicting survival and disease progression in patients with diffuse
      large B-cell lymphoma, considering type of therapy (chemotherapy with or without
      radiation therapy). METHODS AND MATERIALS: We retrospectively evaluated 294
      patients with histologically confirmed diffuse large B-cell lymphoma with respect
      to age, sex, disease stage, International Prognostic Index score, mid-therapy PET
      findings (positive or negative), and disease status after therapy and at last
      follow-up. Overall survival (OS) and progression-free survival (PFS) were
      compared according to mid-therapy PET findings. RESULTS: Of the 294 patients, 163
      (55%) were male, 144 (49%) were age >61 years, 110 (37%) had stage I or II
      disease, 219 (74%) had International Prognostic Index score <=2, 216 (73%)
      received >=6 cycles of rituximab, cyclophosphamide, doxorubicin, vincristine, and
      prednisone, and 88 (30%) received consolidation radiation therapy. Five-year PFS
      and OS rates were associated with mid-therapy PET status: PFS was 78% for those
      with PET-negative (PET-) disease versus 63% for PET-positive (PET+) disease
      (P=.024), and OS was 82% for PET- versus 62% for PET+ (P<.002). These
      associations held true for patients who received chemotherapy only (PFS 71% for
      PET- vs 52% PET+ [P=.012], OS 78% for PET- and 51% for PET+ [P=.0055]) but not
      for those who received consolidation radiation therapy (PFS 84% PET- vs 81% PET+
      [P=.88]; OS 90% PET- vs 81% PET+ [P=.39]). CONCLUSION: Mid-therapy PET can
      predict patient outcome, but the use of consolidation radiation therapy may
      negate the significance of mid-therapy findings.

PMID- 24721594
TI  - Deciphering the interaction of a model transport protein with a prototypical
      imidazolium room temperature ionic liquid: effect on the conformation and
      activity of the protein.
AB  - The present contribution reports the interaction of a prototypical surface-active
      room temperature ionic liquid (RTIL) viz., 1-butyl-3-methylimidazolium
      tetrafluoroborate ([BMIM][BF4]) with a globular transport protein bovine serum
      albumin (BSA). The BSA-RTIL binding isotherm constructed from conductometric
      measurements is found to be well reproduced from fluorescence spectroscopy and
      thus revealing the various interaction zones as a function of the RTIL
      concentration. The present work delivers particular emphasis to delineate the
      denaturing action of RTIL on the native protein and in complementarity the effect
      of RTIL binding on functionality of BSA is explored in terms of esterase-like
      activity of BSA. The intrinsic time-resolved fluorescence decay and rotational
      relaxation dynamics of the protein suggests swelling of the protein rather than
      aggregation during RTIL-induced denaturation. The result of molecular modeling
      based on blind docking simulation is found to abet the inferences drawn from
      experimental results reasonably well. The molecular modeling technique reveals
      the favorable binding location of the RTIL to be in the hydrophobic domain IIIA
      (drug site 2) of BSA. The thermodynamic parameters evaluated for the RTIL-BSA
      binding phenomenon also identifies the pivotal role of hydrophobic force in the
      interaction. 

PMID- 24721595
TI  - An electron spin resonance study of non-ionic surfactant vesicles (niosomes).
AB  - Certain non-ionic surfactants form lamellar vesicles called niosomes. Being
      elastic and deformable, niosomes have been used as an efficient vehicle for
      transdermal drug delivery. However, dynamic properties of niosomes have not been
      studied extensively. In this study we used electron spin resonance (ESR)
      technique to measure the membrane fluidity of niosomes. In parallel with
      phospholipid liposomes, the ESR spectra of 5- and 16-doxyl stearate in niosomes
      of sorbitan monostearate (Span 60) and sorbitan monooleate (Span 80) showed that
      motion of the spin label was more restricted at the region near the headgroup
      than near the bilayer center. Cholesterol increased fluidity of Span 60 niosomes
      whereas it decreased fluidity of Span 80 niosomes. Dicetyl phosphate added at 10
      mol% concentration as a stabilizer had a minimal effect on the membrane fluidity
      throughout the bilayer. We also used ESR technique to monitor the hydration
      induced transformation of Span 60 proniosome gel to niosome and showed that the
      niosome prepared by hydration of proniosome gel was identical to the niosome
      obtained from a thin film hydration method. Finally the ESR spectra of Span
      niosomes were compared with those of polysorbate (Tween) niosomes and polyethoxy
      fatty ether (Brij) niosomes. Tween niosomes had a bulky headgroup and were much
      less rigid than Span niosomes. This effect of headgroup size on fluidity was also
      manifest in Brij niosomes where fluidity increased with the number of ethoxy
      units in the polyethoxy headgroup.

PMID- 24721596
TI  - Soil mesocosm studies on atrazine bioremediation.
AB  - Accumulation of pesticides in the environment causes serious issues of
      contamination and toxicity. Bioremediation is an ecologically sound method to
      manage soil pollution, but the bottleneck here, is the successful scale-up of lab
      scale experiments to field applications. This study demonstrates pilot-scale
      bioremediation in tropical soil using atrazine as model pollutant. Mimicking
      field conditions, three different bioremediation strategies for atrazine
      degradation were explored. 100 kg soil mesocosms were set-up, with or without
      atrazine application history. Natural attenuation and enhanced bioremediation
      were tested, where augmentation with an atrazine degrading consortium
      demonstrated best pollutant removal. 90% atrazine degradation was observed in six
      days in soil previously exposed to atrazine, while soil without history of
      atrazine use, needed 15 days to remove the same amount of amended atrazine. The
      bacterial consortium comprised of 3 novel bacterial strains with different
      genetic atrazine degrading potential. The progress of bioremediation was
      monitored by measuring the levels of atrazine and its intermediate, cyanuric
      acid. Genes from the atrazine degradation pathway, namely, atzA, atzB, atzD, trzN
      and trzD were quantified in all mesocosms for 60 days. The highest abundance of
      all target genes was observed on the 6th day of treatment. trzD was observed in
      the bioaugmented mesocosms only. The bacterial community profile in all mesocosms
      was monitored by LH-PCR over a period of two months. Results indicate that the
      communities changed rapidly after inoculation, but there was no drastic change in
      microbial community profile after 1 month. Results indicated that efficient
      bioremediation of atrazine using a microbial consortium could be successfully up
      scaled to pilot scale. 

PMID- 24721597
TI  - High tibial osteotomy: closed wedge versus combined wedge osteotomy.
AB  - BACKGROUND: High tibial osteotomy is a common procedure to treat symptomatic
      osteoarthritis of the medial compartment of the knee with varus alignment. This
      is achieved by overcorrecting the varus alignment to 2-6 degrees  of valgus.
      Various high tibial osteotomy techniques are currently used to this end. Common
      procedures are medial opening wedge and lateral closing wedge tibial osteotomies.
      The lateral closing wedge technique is a primary stable correction with a high
      rate of consolidation, but has the disadvantage of bone loss and change in tibial
      condylar offset. The medial opening wedge technique does not result in any bone
      loss but needs to be fixated with a plate and may cause tibial slope and medial
      collateral ligament tightening. A relatively new technique, the combined valgus
      high tibial osteotomy, claims to include the advantages of both techniques
      without bone loss. Aim of this prospective randomized trial is to compare the
      lateral closing wedge with the combined wedge osteotomy in patients with
      symptomatic varus osteoarthritis of the knee. METHODS/DESIGN: A group of 110
      patients with osteoarthritis of the medial compartment of the knee with 6-12
      degrees  varus malalignment over 18 years of age are recruited to participate a
      randomized controlled trial. Patients are randomized to undergo a high tibial
      osteotomy, with either a lateral closing wedge technique or a combined wedge
      osteotomy technique. Primary outcome measure is achievement of an overcorrection
      of 4 degrees  valgus after one year of surgery, assessed by measuring the hip
      knee-ankle angle. Secondary objectives are radiological scores and anatomical
      changes after high tibial osteotomy; pain, functional scores and quality of life
      will also be compared. DISCUSSION: Combined high tibial osteotomy modification
      avoids metaphyseal tibial bone loss, decreasing transposition of the tibial
      condyle and shortening of the patellar tendon after osteotomy, even in case of
      great correction. The clinical results of the combined wedge osteotomy technique
      are very promising. Hypothesis is that the combined wedge osteotomy technique
      will achieve more accurate overcorrection of varus malalignment with fewer
      anatomical changes of the proximal tibia after one year. TRIAL REGISTRATION:
      Dutch Trial Registry (Netherlands trial register): NTR3898.

PMID- 24721598
TI  - The critical role of myeloid-derived suppressor cells and FXR activation in
      immune-mediated liver injury.
AB  - The immunobiology of FXR has attracted significant attention in immune regulation
      and innate immunity. We have studied the mechanism of action of FXR activation on
      two models of acute hepatitis, inflammation mediated by Con A and alpha-GalCer
      and focused on the interactions of FXR activation and expression of PIR-B, both
      in vivo and in vitro using luciferase reporter and CHIP assays. In addition,
      based upon our data, we studied the role of FXR activation on the immunobiology
      of myeloid-derived suppressor cells (MDSCs). Importantly, we report herein that
      FXR activation reduces the inflammatory insult induced by either alpha-GalCer or
      Con A; such treatment expands CD11b(+)Ly6C(+) MDSCs. The protective effect of FXR
      activation is dependent on expansion of MDSCs, particularly liver
      CD11b(+)Ly6C(high) cells. Indeed, FXR activation enhances the suppressor function
      of MDSCs through upregulation of PIR-B by binding the PIR-B promoter. FXR
      activation drives the accumulation of MDSCs to liver through upregulation of
      S100A8. FXR activation facilitates homing and function of MDSCs, which function
      as a critical negative feedback loop in immune-mediated liver injury. The novel
      mechanisms defined herein emphasize not only the importance of liver lymphoid
      subpopulations, but also the potential roles of modulating FXR in autoimmune
      liver disease. 

PMID- 24721599
TI  - Nurses' and community support workers' experience of telehealth: a longitudinal
      case study.
AB  - BACKGROUND: Introduction of telehealth into the healthcare setting has been
      recognised as a service that might be experienced as disruptive. This paper
      explores how this disruption is experienced. METHODS: In a longitudinal
      qualitative study, we conducted focus group discussions prior to and semi
      structured interviews post introduction of a telehealth service in Nottingham,
      U.K. with the community matrons, congestive heart failure nurses, chronic
      obstructive pulmonary disease nurses and community support workers that would be
      involved in order to elicit their preconceptions and reactions to the
      implementation. RESULTS: Users experienced disruption due to the implementation
      of telehealth as threatening. Three main factors add to the experience of threat
      and affect the decision to use the technology: change in clinical routines and
      increased workload; change in interactions with patients and fundamentals of face
      to-face nursing work; and change in skills required with marginalisation of
      clinical expertise. CONCLUSION: Since the introduction of telehealth can be
      experienced as threatening, managers and service providers should aim at
      minimising the disruption caused by taking the above factors on board. This can
      be achieved by employing simple yet effective measures such as: providing timely,
      appropriate and context specific training; provision of adequate technical
      support; and procedures that allow a balance between the use of telehealth and
      personal visit by nurses delivering care to their patients.

PMID- 24721601
TI  - Musculoskeletal occupational injury among surgeons: effects for patients,
      providers, and institutions.
AB  - BACKGROUND: The aim of this study was to determine the risk of occupational
      musculoskeletal injury during a surgeon's career and the effects of these
      injuries for patients, providers, and institutions. We hypothesized that surgeons
      have occupational injuries, which affect work performance. MATERIALS AND METHODS:
      Electronic RedCAP surveys on workplace injury were distributed statewide via e
      mail to the members of the Tennessee chapter of the American College of Surgeons.
      Descriptive statistics were used to analyze survey data. RESULTS: A total of 260
      of 793 surveys (33%) were returned. Forty percent of surgeons sustained >= 1
      injuries in the workplace. Although 50% of injured surgeons received medical care
      for their most recent injuries, only 20% of these injuries were reported to their
      institution. Twenty-two percent of injured surgeons missed work and 35% performed
      fewer operations while they were recovering from their injury. Fifty-three
      percent of injured surgeons reported that pain from their injury had a minimal or
      moderate effect on their performance in the operating room. CONCLUSIONS: Surgeons
      appear to be at moderate risk for occupation-related injuries. The low rate of
      institutional reporting for these injuries is concerning, as this is a required
      step to access institutional support once injured. Surgeon injury results in lost
      productivity due to missed workdays and may impact the quality of surgical care
      because of performance issues while recovering from injury.

PMID- 24721600
TI  - Novel expression profiles of microRNAs suggest that specific miRNAs regulate gene
      expression for the sexual maturation of female Schistosoma japonicum after
      pairing.
AB  - BACKGROUND: Schistosoma japonicum is one of the major causative agents of
      schistosomiasis. The pairing of males and females leads to female sexual
      maturation and maintains this mature state. However, the mechanisms by which
      pairing facilitates sexual maturation are yet to be investigated. METHODS:
      Parasites isolated from single- and double-sex cercariae-infected mice were
      analyzed by Solexa to uncover pair-regulated miRNA profiles. To reveal the
      biological functions of differentially expressed miRNAs among the samples, we
      predicted the target genes of these differentially expressed miRNAs and compared
      the gene expression between 23-d-old female schistosomula from double-sex
      infections (23DSI) and 23-d-old female schistosomula from single-sex infections
      (23SSI) by analyzing digital gene expression profiling (DGE). KEGG pathway
      analysis was used to investigate the relevant biological processes of these
      target genes to understand the significance of differentially expressed miRNAs
      after pairing. RESULTS: The differentially expressed miRNA profiles of female 18-
      and 23-d post-single- and double-sex infections were analysed by Solexa. Similar
      miRNA profiles were observed in 18SSI and 18DSI, with the presence of identically
      expressed high-abundance miRNA, such as miRNA-1, miRNA-71b-5p and let-7. By
      contrast, in 23DSI and 23SSI, most of these high-abundance miRNAs were down
      regulated. Furthermore, among all samples, bantam was distinctly up-regulated in
      23 DSI, and miR-1, miR-71, miR-7-5p, and miR-7 were distinctly up-regulated in
      23SSI. The transcriptomes of 23DSI and 23SSI revealed that the predicted target
      genes of miRNA-1, miRNA-71, miRNA-7, and miR-7-5p were associated with the
      ribonucleoprotein complex assembly and microtubule-based process. Conversely, the
      predicted target genes of bantam were related to the embryo development,
      development of primary sexual characteristics and regulation of transcription.
      KEGG pathway analysis revealed that in unpaired females, the highly-expressed
      miRNA-1, miRNA-71, miRNA-7, and miR-7-5p only inhibited the limited pathways,
      such as proteasome and ribosome assembly. Meanwhile, in paired mature females,
      highly-expressed bantam inhibited more biological pathways, such as the citrate
      cycle, glycolysis, fatty acid biosynthesis and RNA degradation. CONCLUSIONS: The
      differentially expressed miRNAs between 23SSI and 23DSI and their different
      functions indicated that more genes or metabolic pathways in paired mature
      females were inhibited than those in unpaired ones. The results suggested that
      after pairing, specific miRNAs regulated gene expression to lead to female sexual
      maturation.

PMID- 24721603
TI  - Long-term outcomes of extracorporeal shockwave therapy for chronic foot ulcers.
AB  - BACKGROUND: Recent studies showed that extracorporeal shockwave therapy (ESWT) is
      effective in the treatment of chronic foot ulcers in short term. However, the
      long-term effects of ESWT in chronic foot ulcers are unknown. The purpose of this
      study was to evaluate the long-term outcomes of ESWT in chronic foot ulcers with
      5-y follow-up. METHODS: The study cohort consisted of 67 patients with 72 ulcers
      including 38 patients with 40 ulcers in the diabetes mellitus (DM) group and 29
      patients with 32 ulcers in the non-diabetes mellitus (non-DM) group. Each patient
      received ESWT to the affected foot twice per week for 3 wk for a total of six
      treatments. The evaluations included clinical assessment for the ulcer status,
      local blood flow perfusion, and analysis of mortality and morbidity. RESULTS: The
      results showed completely healed ulcers in 55.6% and 57.4% of total series, 48%
      and 43% of DM group, and 66% and 71% of non-DM group at 1 and 5 y (P = 0.022 and
      P = 0.027), respectively. The mortality rate was 15% in total series, 24% in DM
      group, and 3% in non-DM group (P = 0.035). The rate of amputation was 11% in
      total series, 17% in DM group, and 3.6% in non-DM group (P = 0.194). The blood
      flow perfusion rate significantly increased after ESWT for up to 1 yr but
      decreased from 1-5 y in both groups. However, the non-DM group showed
      significantly better blood flow perfusion than the DM group at 5 y (P = 0.04).
      CONCLUSIONS: ESWT appears effective in chronic diabetic and nondiabetic foot
      ulcers. However, the effects decreased from 1-5 y after treatment.

PMID- 24721602
TI  - Three-dimensional printing surgical instruments: are we there yet?
AB  - BACKGROUND: The applications for rapid prototyping have expanded dramatically
      over the last 20 y. In recent years, additive manufacturing has been intensely
      investigated for surgical implants, tissue scaffolds, and organs. There is,
      however, scant literature to date that has investigated the viability of three
      dimensional (3D) printing of surgical instruments. MATERIALS AND METHODS: Using a
      fused deposition modeling printer, an Army/Navy surgical retractor was replicated
      from polylactic acid (PLA) filament. The retractor was sterilized using standard
      Food and Drug Administration approved glutaraldehyde protocols, tested for
      bacteria by polymerase chain reaction, and stressed until fracture to determine
      if the printed instrument could tolerate force beyond the demands of an operating
      room (OR). RESULTS: Printing required roughly 90 min. The instrument tolerated
      13.6 kg of tangential force before failure, both before and after exposure to the
      sterilant. Freshly extruded PLA from the printer was sterile and produced no
      polymerase chain reaction product. Each instrument weighed 16 g and required only
      $0.46 of PLA. CONCLUSIONS: Our estimates place the cost per unit of a 3D-printed
      retractor to be roughly 1/10th the cost of a stainless steel instrument. The PLA
      Army/Navy retractor is strong enough for the demands of the OR. Freshly extruded
      PLA in a clean environment, such as an OR, would produce a sterile ready-to-use
      instrument. Because of the unprecedented accessibility of 3D printing technology
      world wide and the cost efficiency of these instruments, there are far reaching
      implications for surgery in some underserved and less developed parts of the
      world.

PMID- 24721604
TI  - Morbidity of peripherally inserted central catheters in pediatric complicated
      appendicitis.
AB  - BACKGROUND: The purpose of this study was to compare postoperative outcomes of
      pediatric patients with complicated appendicitis managed with or without a
      peripherally inserted central catheter (PICC). METHODS: Patients aged <=18 y in
      the Pediatric Health Information System database with complicated appendicitis
      that underwent appendectomy during their index admission in 2000-2012 were
      grouped by whether they had a PICC placed using relevant procedure and billing
      codes. Rates of subsequent encounters within 30 d of discharge along with
      associated diagnoses and procedures were determined. A propensity score-matched
      (PSM) analysis was performed to account for differences in baseline exposures and
      severity of illness. RESULTS: We included 33,482 patients with complicated
      appendicitis; of whom, 6620 (19.8%) received a PICC and 26,862 (80.2%) did not.
      The PICC group had a longer postoperative length of stay (median 7 versus 5 d,
      P<0.001) and were more likely to undergo intra-abdominal abscess drainage during
      the index admission (14.4% versus 2.1%, P<0.001), and have a reencounter (17.5%
      versus 11.4%, P<0.001) within 30 d of discharge. However, in the PSM cohort
      (n=4428 in each group), outcomes did not differ between treatment groups,
      although the PICC group did have increased odds for the development of other
      postoperative complications (odds ratio=3.95, 95% confidence interval: 1.45,
      10.71). CONCLUSIONS: After accounting for differences in severity of illness by
      PSM, patients managed with PICCs had a similar risk for nearly all postoperative
      complications, including reencounters. Postoperative management of pediatric
      complicated appendicitis with a PICC is not clearly associated with improved
      outcomes.

PMID- 24721605
TI  - Large-for-size liver transplantation: a flowmetry study in pigs.
AB  - BACKGROUND: Ischemia-reperfusion injury is partly responsible for morbidity in
      pediatric liver transplantation. Large-for-size (LFS) liver transplantation has
      not been fully studied in the pediatric population, and the effects of
      reperfusion injury may be underestimated. MATERIALS AND METHODS: Thirteen
      Landrace-Large white pigs weighing 23 kg (range, 17-38 kg) underwent orthotopic
      liver transplantation. They were divided into two groups according to the size of
      the donor body: LFS and control (CTRL). After transplantation, the abdominal
      cavity of the recipient was kept open and portal venous flow (PVF) was measured
      after 1 h. The ratio of recipient PVF (PVFr) to donor PVF was used to establish
      correlations with ischemia and reperfusion parameters. Liver biopsies were taken
      1 h after transplantation to assess ischemia and reperfusion and to quantify the
      gene expression of endothelial nitric oxide synthase, interleukin 6, BAX, and
      BCL. RESULTS: Recipient weight, total ischemia time, and warm ischemia time were
      similar between groups. Among hemodynamic and metabolic analyses, pH, central
      arteriovenous PCO2 difference, and AST were statistically worse in the LFS group
      than in the CTRL group. The same was found with endothelial nitric oxide synthase
      (0.41 +/- 0.18 versus 1.56 +/- 0.78; P = 0.02) and interleukin 6 (4.66 +/- 4.61
      versus 16.21 +/- 8.25; P = 0.02). In the LFS group, a significant decay in the
      PVFr was observed in comparison with the CTRL group (0.93 +/- 0.08 and 0.52 +/-
      0.11, respectively; P < 0.001). CONCLUSIONS: The implantation of a graft was
      responsible for poor hemodynamic status of the recipient 1 h after
      transplantation. Furthermore, the LFS group demonstrated markers of ischemia and
      reperfusion that were worse when compared with the CTRL group and exhibited a
      more significant decrease in PVF from donor to recipient.

PMID- 24721606
TI  - Oxygen consumption predicts outcome in porcine partial liver grafts.
AB  - BACKGROUND: High oxygen consumption (OC) in recipients of cadaveric whole liver
      grafts is associated with a poor prognosis. The aim of this study is to
      investigate the relationship between intraoperative hepatic OC and graft function
      and survival in a porcine partial liver graft model. MATERIAL AND METHODS:
      Experiments followed the Guiding Principles in the Care and Use of Laboratory
      Animals. Fourteen female pigs, 46-69 kg, received liver allografts of 17%-39%
      liver volume and were followed for 14 d. We measured donor and recipient body
      weights, percentage graft weight and expressed it as a percentage of standard
      liver volume, cold ischemia time, hepatic artery flow (HAF), portal vein flow
      (PVF), graft volume at sacrifice, serum lactate, prothrombin time, aspartate
      aminotransferase (AST), alanine aminotransferase (ALT), creatinine, albumin,
      total protein, alkaline phosphatase, total bilirubin, and recipient survival. OC
      was calculated as follows: OC (mL/100 g/min) = ([Hemoglobin {Hb} * 1.34 * SaO2 +
      0.003 * PaO2] * HAF + [Hb * 1.34 * SpO2 + 0.003 * PpO2] * PVF - [Hb * 1.34 * SvO2
      + 0.003 * PvO2] * [HAF + PVF])/graft weight (100 g), and animals were divided
      into two groups: low OC group (OC < 2.0 mL/100 g/min) and high OC group (OC >=
      2.0 mL/100 g/min). RESULTS: In survival analysis, four of seven low OC recipients
      (57% [n = 7]) survived until the end of the study period compared with one of
      seven high OC recipients (14% [n = 7]). The low OC group had a significantly
      higher survival rate than that of the high OC group (P = 0.041). Low OC was
      associated with higher HAF (mL/100 g/min) after reperfusion compared with that of
      the high OC group, 29.0 +/- 13.8 versus 16.0 +/- 11.1 mean +/- standard
      deviation; P = 0.073. Serum alkaline phosphatase and total bilirubin in the low
      OC group were significantly better than those of the high OC group. Serum lactate
      was comparable in both groups. Graft weight at the time of sacrifice in the low
      OC group tended to be higher than that in the high OC group, but not
      significantly (P = 0.097). CONCLUSIONS: High intraoperative OC is associated with
      lower HAF, decreased graft function, and decreased survival in the porcine
      partial liver graft model.

PMID- 24721608
TI  - Hailey-Hailey disease diagnosed based on an exacerbation of contact dermatitis
      with topical crotamiton.

PMID- 24721607
TI  - Anti-angiogenic actions of the mangosteen polyphenolic xanthone derivative alpha
      mangostin.
AB  - Retinal neovascularization is a major cause of vision loss in diseases
      characterized by retinal ischemia and is characterized by the pathological growth
      of abnormal vessels. Vascular endothelial growth factor (VEGF) is known to play
      an important role in this process. Oxidative stress has been strongly implicated
      in up-regulation of VEGF associated with neovascularization in various tissues.
      Hence, compounds with anti-oxidant actions can prevent neovascularization. alpha
      Mangostin, a component of mangosteen (Garcinia mangostana Linn), has been shown
      to have an anti-oxidant property in pathological conditions involving
      angiogenesis such as cancer. However, the effect of alpha-mangostin on ROS
      formation and angiogenic function in microvascular endothelial cells has not been
      studied. Hence, this study demonstrated the anti-angiogenic effects of alpha
      mangostin in relation to ROS formation in bovine retinal endothelial cells (REC).
      alpha-Mangostin significantly and dose-dependently reduced formation of ROS in
      hypoxia-treated REC. alpha-Mangostin also significantly and dose-dependently
      suppressed VEGF-induced increases in permeability, proliferation, migration and
      tube formation in REC and blocked angiogenic sprouting in the ex vivo aortic ring
      assay. In addition, alpha-mangostin inhibited VEGF-induced phosphorylation of
      VEGFR2 and ERK1/2-MAPK. According to our results, alpha-mangostin reduces
      oxidative stress and limits VEGF-induced angiogenesis through a process involving
      abrogation of VEGFR2 and ERK1/2-MAPK activation. 

PMID- 24721609
TI  - Adult, but not neonatal, human lymphoid progenitors respond to TLR9 ligation by
      producing functional NK-like cells.
AB  - Remarkable progress has been made in characterizing factors controlling lineage
      fate decisions of primitive progenitors that initiate the lymphoid program in
      bone marrow. However, the understanding of neonatal/adult differences in
      environmental signals that influence differentiation pathway stability is still
      incomplete. Our recent findings suggest that Toll-like receptors provide a
      mechanism for producing cells of the innate immune system from early stages of
      lymphoid development in mice. We now show that both human early multilymphoid
      progenitors and more differentiated lymphoid progenitors from normal adult bone
      marrow express TLR9. Furthermore, they respond to its ligation by upregulating
      the expression of IL-15Rbeta (CD122) and accelerating the production of
      functional natural killer (NK)-like cells. Proliferation of the presumed
      equivalent progenitor cells from umbilical cord blood was stimulated by CpG
      containing oligonucleotides or herpes simplex virus, but the already robust NK
      cell formation was unchanged. This new information adds to other known
      differences between neonatal and adult lymphoid progenitors and suggests only the
      latter replenish innate NK-like cells in response to Toll-like receptor agonists.

PMID- 24721610
TI  - Mobilization with granulocyte colony-stimulating factor blocks medullar
      erythropoiesis by depleting F4/80(+)VCAM1(+)CD169(+)ER-HR3(+)Ly6G(+) erythroid
      island macrophages in the mouse.
AB  - Similarly to other tissues, the bone marrow contains subsets of resident tissue
      macrophages, which are essential to maintain bone formation, functional
      hematopoietic stem cell (HSC) niches, and erythropoiesis. Pharmacologic doses of
      granulocyte colony-stimulating factor (G-CSF) mobilize HSC in part by interfering
      with the HSC niche-supportive function of BM resident macrophages. Because bone
      marrow macrophages are key to both maintenance of HSC within their niche and
      erythropoiesis, we investigated the effect of mobilizing doses of G-CSF on
      erythropoiesis in mice. We now report that G-CSF blocks medullar erythropoiesis
      by depleting the erythroid island macrophages we identified as co-expressing
      F4/80, vascular cell adhesion molecule-1, CD169, Ly-6G, and the ER-HR3 erythroid
      island macrophage antigen. Both broad macrophage depletion, achieved by injecting
      clodronate-loaded liposomes, and selective depletion of CD169(+) macrophages,
      also concomitantly depleted F4/80(+)VCAM-1(+)CD169(+)ER-HR3(+)Ly-6G(+) erythroid
      island macrophages and blocked erythropoiesis. This more precise phenotypic
      definition of erythroid island macrophages will enable studies on their biology
      and function in normal settings and on diseases associated with anemia. Finally,
      this study further illustrates that macrophages are a potent relay of innate
      immunity and inflammation on bone, hematopoietic, and erythropoietic maintenance.
      Agents that affect these macrophages, such as G-CSF, are likely to affect these
      three processes concomitantly. 

PMID- 24721611
TI  - Ulcus vulvae acutum Lipschutz in two young female patients.
AB  - Ulcus vulvae acutum Lipschutz or acute genital ulcer is a distinct clinical
      entity characterized by sudden painful genital ulceration occurring mostly in
      young and virgin girls with malaise, fever and other systemic symptoms. This
      distressing syndrome is rare and may be presented to dermatologists,
      gynecologists or pediatricians. Its diagnosis and therapy can be challenging. We
      present two young female patients with ulcus vulvae acutum. The cause of the
      disease could not be confirmed in our patients, but, interestingly, both patients
      had partial IgA deficiency. In the last 100 years, after its first description by
      Lipschutz, many case reports and series have aimed to identify a specific cause
      of the disease, without success. These studies mainly focused on infectious
      agents as causative factors, however, in most cases connection with infection
      could not be confirmed. Our opinion is that the decreased level of IgA could be a
      possible explanation for the cause of this syndrome. With our cases we would like
      to emphasize the possible role of local immunological mechanisms rather than
      several infectious agents in the development of this little-known disease. 

PMID- 24721612
TI  - Galloyl moieties enhance the dentin biomodification potential of plant-derived
      catechins.
AB  - Proanthocyanidin-rich plant-derived agents have been shown to enhance dentin
      biomechanical properties and resistance to collagenase degradation. This study
      systematically investigated the interaction of chemically well-defined monomeric
      catechins with dentin extracellular matrix components by evaluating dentin
      mechanical properties as well as activities of matrix metalloproteinases (MMPs)
      and cysteine-cathepsins (CTs). Demineralized dentin beams (n=15) were incubated
      for 1h with 0.65% (+)-catechin (C), (-)-catechin gallate (CG), (-)-gallocatechin
      gallate (GCG), (-)-epicatechin (EC), (-)-epicatechin gallate (ECG), (-)
      epigallocatechin (EGC) and (-)-epigallocatechin-3-gallate (EGCG). The modulus of
      elasticity (E) and the fold increase in E were determined by comparing specimens
      at baseline and after treatment. Biodegradation rates were assessed by
      differences in percentage of dry mass before and after incubation with bacterial
      collagenase. The inhibition of MMP-9 and CT-B by 0.65, 0.065 and 0.0065% of each
      catechin was determined using fluorimetric proteolytic assay kits. All monomeric
      catechins led to a significant increase in E. EGCG showed the highest fold
      increase in E, followed by ECG, CG and GCG. EGCG, ECG, GCG and CG significantly
      lowered biodegradation rates and inhibited both MMP-9 and CT-B at a concentration
      of 0.65%. Overall, the 3-O-galloylated monomeric catechins are clearly more
      potent than their non-galloylated analogues in improving dentin mechanical
      properties, stabilizing collagen against proteolytic degradation, and inhibiting
      the activity of MMPs and CTs. The results indicate that galloylation is a key
      pharmacophore in the monomeric and likely also in the oligomeric
      proanthocyanidins that exhibit high cross-linking potential for dentin
      extracellular matrix. 

PMID- 24721614
TI  - The impact of a reformulation of extended-release oxycodone designed to deter
      abuse in a sample of prescription opioid abusers.
AB  - BACKGROUND: Prescription opioid abuse is a significant public health concern that
      requires strategies to reduce its impact, including development of abuse
      deterrent formulations. OxyContin, an extended-release oxycodone (ERO)
      formulation, has been widely abused. This study assessed the effects of
      reformulated ERO, designed to be more difficult to manipulate for purposes of
      intranasal and intravenous abuse, on patterns of opioid abuse among a sample of
      individuals from rural Appalachia with a history of ERO abuse. METHODS:
      Structured interviews assessing opioid abuse (past 30-day abuse and
      retrospectively reported abuse prior to the reformulation in August 2010) were
      completed by 189 individuals between December 2010 and September 2011. RESULTS:
      The past 30-day prevalence and frequency of reformulated ERO abuse through any
      route (33%, 1.9 days/month), snorting (5%, 0.2 days/month), and injecting (0.5%,
      <0.1 days/month) were low and infrequent compared to that of IR oxycodone (any
      route: 96%, 19.5 days/month; snorting: 70%, 10.3 days/month; injecting: 51%, 10.5
      days/month) and retrospectively reported abuse of original ERO in August 2010
      (any route: 74%, 13.4 days/month; snorting: 39%, 6.0 days/month; injecting: 41%,
      8.6 days/month). After the reformulation, the prevalence of original ERO abuse
      significantly declined while abuse of reformulated ERO remained steadily low.
      Heroin abuse was rare in this sample. CONCLUSIONS: In this sample, abuse of
      reformulated ERO was low, and lower than abuse of original ERO retrospectively
      and IR oxycodone concurrently, particularly through injecting and snorting routes
      of administration. There was no evidence to suggest that reformulated ERO became
      a substitute for original ERO.

PMID- 24721615
TI  - Per-protocol effect of earlier non-pneumatic anti-shock garment application for
      obstetric hemorrhage.

PMID- 24721613
TI  - Implant osseointegration and the role of microroughness and nanostructures:
      lessons for spine implants.
AB  - The use of spinal implants for spine fusion has been steadily increasing to avoid
      the risks of complications and donor site morbidity involved when using
      autologous bone. A variety of fusion cages are clinically available, with
      different shapes and chemical compositions. However, detailed information about
      their surface properties and the effects of such properties on osteogenesis is
      lacking in the literature. Here we evaluate the role of surface properties for
      spinal implant applications, covering some of the key biological processes that
      occur around an implant and focusing on the role of surface properties,
      specifically the surface structure, on osseointegration, drawing examples from
      other implantology fields when required. Our findings revealed that surface
      properties such as microroughness and nanostructures can directly affect early
      cell behavior and long-term osseointegration. Microroughness has been well
      established in the literature to have a beneficial effect on osseointegration of
      implants. In the case of the role of nanostructures, the number of reports is
      increasing and most studies reveal a positive effect from the nanostructures
      alone and a synergistic effect when combined with microrough surfaces. Long-term
      clinical results are nevertheless necessary to establish the full implications of
      surface nanomodifications. 

PMID- 24721616
TI  - Rebound increase in vaginal delivery for twins in a regional obstetric unit in
      Hong Kong.

PMID- 24721617
TI  - Deformable models with sparsity constraints for cardiac motion analysis.
AB  - Deformable models integrate bottom-up information derived from image appearance
      cues and top-down priori knowledge of the shape. They have been widely used with
      success in medical image analysis. One limitation of traditional deformable
      models is that the information extracted from the image data may contain gross
      errors, which adversely affect the deformation accuracy. To alleviate this issue,
      we introduce a new family of deformable models that are inspired from the
      compressed sensing, a technique for accurate signal reconstruction by harnessing
      some sparseness priors. In this paper, we employ sparsity constraints to handle
      the outliers or gross errors, and integrate them seamlessly with deformable
      models. The proposed new formulation is applied to the analysis of cardiac motion
      using tagged magnetic resonance imaging (tMRI), where the automated tagging line
      tracking results are very noisy due to the poor image quality. Our new deformable
      models track the heart motion robustly, and the resulting strains are consistent
      with those calculated from manual labels. 

PMID- 24721619
TI  - Cochrane review questions effectiveness of neuraminidase inhibitors.

PMID- 24721618
TI  - The effect of differing Gleason scores at biopsy on the odds of upgrading and the
      risk of death from prostate cancer.
AB  - INTRODUCTION/BACKGROUND: The GS is an established prostate cancer prognostic
      factor. Whether the presence of differing GSs at biopsy (eg, 4+3 and 3+3), which
      we term ComboGS, improves the prognosis that would be predicted based on the
      highest GS (eg, 4+3) because of decreased upgrading is unknown. Therefore, we
      evaluated the odds of upgrading at time of radical prostatectomy (RP) and the
      risk of PCSM when ComboGS was present versus absent. PATIENTS AND METHODS:
      Logistic and competing risks regression were performed to assess the effect that
      ComboGS had on the odds of upgrading at time of RP in the index (n = 134) and
      validation cohorts (n = 356) and the risk of PCSM after definitive therapy in a
      long-term cohort (n = 666), adjusting for known predictors of these end points.
      We calculated and compared the area under the curve using a receiver operating
      characteristic analysis when ComboGS was included versus excluded from the
      upgrading models. RESULTS: ComboGS was associated with decreased odds of
      upgrading (index: adjusted odds ratio [AOR], 0.14; 95% confidence interval [CI],
      0.04-0.50; P = .003; validation: AOR, 0.24; 95% CI, 0.11-0.51; P < .001) and
      added significantly to the predictive value of upgrading for the in-sample index
      (P = .02), validation (P = .003), and out-of-sample prediction models (P = .002).
      ComboGS was also associated with a decreased risk of PCSM (adjusted hazard ratio,
      0.40; 95% CI, 0.19-0.85; P = .02). CONCLUSION: Differing biopsy GSs are
      associated with a lower odds of upgrading and risk of PCSM. If validated, future
      randomized noninferiority studies evaluating deescalated treatment approaches in
      men with ComboGS could be considered.

PMID- 24721620
TI  - 1,25-dihydroxyvitamin D and PTHrP mediated malignant hypercalcemia in a seminoma.
AB  - BACKGROUND: Seminomas have been rarely associated with malignant hypercalcemia.
      The responsible mechanism of hypercalcemia in this setting has been described to
      be secondary to 1,25-dihydroxyvitamin D secretion. The relationship with PTHrP
      has not been determined or studied.The aim of this study is to describe and
      discuss the case and the pathophysiological mechanisms involved in a malignant
      hypercalcemia mediated by 1,25-dihydroxyvitamin D and PTHrP cosecretion in a
      patient with seminoma. CASE PRESENTATION: A 35-year-old man was consulted for
      assessment and management of severe hypercalcemia related to an abdominal mass.
      Nausea, polyuria, polydipsia, lethargy and confusion led him to the emergency
      department. An abdominal and pelvic enhanced CT confirmed a calcified pelvic
      mass, along with multiple retroperitoneal lymphadenopathy. Chest x-ray revealed
      "cannon ball" pulmonary metastases. The histopathology result was consistent with
      a seminoma. Serum calcium was 14.7 mg/dl, PTH was undetectable, 25
      dihydroxyvitamin D was within normal values and PTHrP and 1,25-dihydroxyvitamin
      were elevated (35.0 pg/ml, and 212 pg/ml, respectively). After the first cycle of
      chemotherapy with bleomycin, etoposide and cisplatin, normocalcemia was restored.
      Both PTHrP and 1,25-dihydroxyvitamin D, dropped dramatically to 9.0 pg/ml and 8.0
      pg/ml, respectively. CONCLUSION: The association of seminoma and malignant
      hypercalcemia is extremely rare. We describe a case of a patient with a seminoma
      and malignant hypercalcemia related to paraneoplastic cosecretion of 1,25
      dihydroxyvitamin D and PTHrP. After successful chemotherapy, calcium, PTHrP and
      1,25-Dihydroxyvitamin D returned to normal values.

PMID- 24721621
TI  - Cervical cancer prevention in reproductive health services: knowledge, attitudes
      and practices of midwives in Cote d'Ivoire, West Africa.
AB  - BACKGROUND: Cervical cancer is the most common cancer among women and the leading
      cause of cancer deaths in women in Cote d'Ivoire. Low resource countries can now
      prevent this cancer by using HPV vaccine and effective and affordable screening
      tests. However the implementation of these prevention strategies needs well
      trained human resources. Part of the solution could come from midwives by
      integrating cervical cancer prevention into reproductive health services. The aim
      of this survey was to assess knowledge, attitudes and practices of midwives
      towards cervical cancer prevention in Abidjan, Cote d'Ivoire, and to find out
      factors associated with appropriate knowledge. METHODS: A cross-sectional survey
      was conducted among midwives in the urban district of Abidjan, using a self
      administered questionnaire. Knowledge was assessed by two scores. Factors
      associated with appropriate knowledge were determined using a logistic regression
      analysis. Attitudes and practices were described and compare using the Chi2 test.
      RESULTS: A total of 592 midwives were enrolled, including 24.5% of final-year
      students. 55.7% of midwives had appropriate knowledge on cervical cancer, and
      42.4% of them had appropriate knowledge on cervical cancer prevention strategies.
      Conferences, courses taken at school of midwifery and special training sessions
      on cervical cancer (OR = 4.9, 95% CI [1.9 to 12.6], p <0.01) were associated with
      good knowledge on the management of this disease. Among these midwives, 18.4% had
      already benefited from a screening test for themselves, 37.7% had already advised
      screening to patients and 8.4% were able to perform a visual inspection. 50.3% of
      midwives knew HPV vaccine as a preventive method; among them 70.8% usually
      recommended it to young girls. CONCLUSION: Despite sufficient knowledge about
      cervical cancer prevention, attitudes and practices of midwives should be
      improved by organizing capacity building activities. This would ensure the
      success of integration of cervical cancer prevention into reproductive health
      services in countries like Cote d'Ivoire.

PMID- 24721622
TI  - Epidermal growth factor induces platelet-activating factor production through
      receptors transactivation and cytosolic phospholipase A2 in ovarian cancer cells.
AB  - BACKGROUND: Among the pro-inflammatory lipid mediators, platelet-activating
      factor (PAF) is a major primary and secondary messenger that binds to the PAF
      receptor (PAFR). Epidermal growth factor (EGF) is a polypeptide growth factor
      that binds to the EGF-receptor (EGFR). Evidence suggests that both PAF and EGF
      play a significant role in oncogenic transformation, tumor growth,
      neoangiogenesis and metastasis, including ovarian cancer. PAF has the potential
      to transactivate EGFR in ovarian cancer cells. This study explores the mechanisms
      involved in EGF-induced PAF production. METHODS: The effect of EGF on PAF
      production in ovarian cancer cells was observed using enzyme-linked immunosorbent
      assay. The receptors transactivation and the role of cytosolic phospholipase A2
      (cPLA2) in modulating PAF production induced by EGF was assessed using
      pharmacological inhibitors, si-RNA knockdown, targeted gene overexpression and
      immunocytochemistry. The signaling pathways invovled in PAF production induced by
      EGF in ovarian cancer cells were assessed. RESULTS: We demonstrate that EGF
      increases the production of PAF in CAOV3 and SKOV3 ovarian cancer cell lines. EGF
      induces the transactivation of PAFR, which can be blocked by an EGFR inhibitor.
      Inhibition of EGFR and/or PAFR blocks PAF production in response to EGF. EGF
      induced PAF production involves the phosphorylation of extracellular-regulated
      protein kinase (ERK) and cytosolic phospholipase A2 (cPLA2). A cPLA2 inhibitor
      blocks EGF-induced PAF production as well as si-cPLA2, while overexpression of
      cPLA2 increases PAF production. CONCLUSIONS: These results indicate that EGF
      stimulates PAF production in ovarian cancer cells in a manner that requires
      cPLA2. We have also determined that crosstalk can occur bidirectionally between
      EGFR and PAFR, suggesting that EGF-induced PAF production could result in
      positive feedback that acts on the PAF-receptor to promote ovarian cancer
      progression.

PMID- 24721623
TI  - Dynamic stock and end-of-life flow identification based on the internal cycle
      model and mean-age monitoring.
AB  - Planning of end-of-life (EoL) product take-back systems and sizing of dismantling
      and recycling centers, entails the EoL flow (EoLF) that originates from the
      product dynamic stock (DS). Several uncertain factors (economic, technological,
      health, social and environmental) render both the EoLF and the remaining stock
      uncertain. Early losses of products during use due to biodegradation, wear and
      uncertain factors such as withdrawals and exports of used, may diminish the stock
      and the EoLF. Life expectancy prediction methods are static, ignoring early
      losses and inapt under dynamic conditions. Existing dynamic methods, either
      consider a single uncertain factor (e.g. GDP) approximately or heuristically
      modelled and ignore other factors that may become dominant, or assume cognizance
      of DS and of the center axis of the EoL exit distribution that are unknown for
      most products. As a result, reliable dynamic EoLF prediction for both durables
      and consumer end-products is still challenging. The present work develops an
      identification method for estimating the early loss and DS and predicting the
      dynamic EoLF, based on available input data (production+net imports) and on
      sampled measurements of the stock mean-age and the EoLF mean-age. The mean ages
      are scaled quantities, slowly varying, even under dynamic conditions and can be
      reliably determined, even from small size and/or frequent samples. The method
      identifies the early loss sequence, as well as the center axis and spread of the
      EoL exit distribution, which are subsequently used to determine the DS and EoLF
      profiles, enabling consistent and reliable predictions. 

PMID- 24721624
TI  - Disseminated porokeratosis transiently healed by cancer chemotherapy.

PMID- 24721625
TI  - Chronic nandrolone decanoate exposure during adolescence affects emotional
      behavior and monoaminergic neurotransmission in adulthood.
AB  - Nandrolone decanoate, an anabolic androgen steroid (AAS) illicitly used by adult
      and adolescent athletes to enhance physical performance and body image, induces
      psychiatric side effects, such as aggression, depression as well as a spectrum of
      adverse physiological impairments. Since adolescence represents a
      neurodevelopmental window that is extremely sensitive to the detrimental effects
      of drug abuse, we investigated the long-term behavioral and neurophysiological
      consequences of nandrolone abuse during adolescence. Adolescent rats received
      daily injections of nandrolone decanoate (15 mg/kg, i.m.) for 14 days (PND 40
      53). At early adulthood (PND 68), forced swim, sucrose preference, open field and
      elevated plus maze tests were performed to assess behavioral changes. In vivo
      electrophysiological recordings were carried out to monitor changes in electrical
      activity of serotonergic neurons of the dorsal raphe nucleus (DRN) and
      noradrenergic neurons of the locus coeruleus (LC). Our results show that after
      early exposure to nandrolone, rats display depression-related behavior,
      characterized by increased immobility in the forced swim test and reduced sucrose
      intake in the sucrose preference test. In addition, adult rats presented anxiety
      like behavior characterized by decreased time and number of entries in the
      central zone of the open field and decreased time spent in the open arms of the
      elevated plus maze. Nandrolone decreased the firing rate of spontaneously active
      serotonergic neurons in the DRN while increasing the firing rate of noradrenergic
      neurons in the LC. These results provide evidence that nandrolone decanoate
      exposure during adolescence alters the emotional profile of animals in adulthood
      and significantly modifies both serotonergic and noradrenergic neurotransmission.

PMID- 24721626
TI  - Phenytoin attenuates the hyper-exciting neurotransmission in cultured embryonic
      cortical neurons.
AB  - Phenytoin is an effective anti-epileptic drug that inhibits Na(+) channel
      activities; however, how phenytoin modulates synaptic transmission to soothe
      epileptic symptoms is not clear. To characterize the effects of phenytoin
      regulation on neurotransmission, we studied the electrophysical properties of
      cultured embryonic cortical neurons. Phenytoin inhibited the inward Na(+) current
      in a dose-dependent manner with an IC50 of 16.8 MUM, and at 100 MUM, the
      inhibitory effect of phenytoin on the Na(+) current was proportional to the
      frequency applied. In cultured neurons, phenytoin significantly decreased the
      action potential firing rate and the peak potential. To study the effect of
      phenytoin in neurotransmission, we measured the Ca(2+) responses from stimulated
      target neurons and their neighboring neurons. Phenytoin significantly suppressed
      the Ca(2+) responses evoked by strong stimulations in the target and neighboring
      neurons, and exerted a decreased inhibitory effect under moderate stimulation.
      Picrotoxin, a GABAA receptor antagonist, enhanced the recorded spontaneous
      excitatory postsynaptic current activities. After picrotoxin-induced enhancement,
      phenytoin had a more pronounced effect on the suppression of the spontaneous
      hyper-exciting excitatory postsynaptic current (>100 pA), but it only mildly
      inhibited the general excitatory postsynaptic current. Our results demonstrate
      that phenytoin suppresses the efficacy of neurotransmission especially for the
      high-frequency stimulation by reducing the Na(+) channel activity and can
      potentially alleviate epileptiform activity. 

PMID- 24721627
TI  - Cholangiocarcionoma and primary sclerosing cholangitis: the answer lies within.

PMID- 24721628
TI  - Developing tools for the assessment of the learning colonoscopist.

PMID- 24721629
TI  - Ileal lines: a marker of the ileocecal valve on wireless capsule endoscopy.

PMID- 24721630
TI  - Technology status evaluation report on wireless capsule endoscopy.

PMID- 24721631
TI  - Bacteremia and sepsis after radiofrequency ablation of gastric antral vascular
      ectasia.

PMID- 24721632
TI  - Response.

PMID- 24721633
TI  - Under-recognition of 22q11.2 deletion in adult Chinese patients with conotruncal
      anomalies: implications in transitional care.
AB  - 22q11.2 deletion syndrome (22q11.2DS) is a multi-systemic disorder with high
      phenotypic variability. Under-diagnosis in adults is common and recognition of
      facial dysmorphic features can be affected by age and ethnicity. This study aims
      to determine the prevalence of undiagnosed 22q11.2DS in adult Chinese patients
      with conotruncal anomalies and to delineate their facial dysmorphisms and extra
      cardiac manifestations. We recruited consecutively 156 patients with conotruncal
      anomalies in an adult congenital heart disease (CHD) clinic in Hong Kong and
      screened for 22q11.2DS using fluorescence-PCR and fluorescence in-situ
      hybridization. Assessment for dysmorphic features was performed by a cardiologist
      at initial screening and then by a clinical geneticist upon result disclosure.
      Clinical photographs were taken and childhood photographs collected. Eighteen
      patients (11.5%) were diagnosed with 22q11.2DS, translating into 1 previously
      unrecognized diagnosis of 22q11.2DS in every 10 adult patients with conotruncal
      anomalies. While dysmorphic features were detected by our clinical geneticist in
      all patients, only two-thirds were considered dysmorphic by our cardiologist upon
      first assessment. Evolution of facial dysmorphic features was noted with age.
      Extra-cardiac manifestations included velopharyngeal incompetence or cleft palate
      (44%), hypocalcemia (39%), neurodevelopmental anomalies (33%), thrombocytopenia
      (28%), psychiatric disorders (17%), epilepsy (17%) and hearing loss (17%). We
      conclude that under-diagnosis of 22q11.2DS in Chinese adults with conotruncal
      defects is common and facial dysmorphic features may not be reliably recognized
      in the setting of adult CHD clinic, referral for genetic evaluation and molecular
      testing for 22q11.2DS should be offered to patients with conotruncal defects.

PMID- 24721634
TI  - Klotho attenuates high glucose-induced fibronectin and cell hypertrophy via the
      ERK1/2-p38 kinase signaling pathway in renal interstitial fibroblasts.
AB  - Although exogenous klotho attenuates renal fibrosis, it is not known if exogenous
      klotho attenuates diabetic nephropathy (DN). Thus, we studied the anti-fibrotic
      mechanisms of klotho in terms of transforming growth factor-beta (TGF-beta) and
      signaling pathways in high glucose (HG, 30 mM)-cultured renal interstitial
      fibroblast (NRK-49F) cells. We found that HG increased klotho mRNA and protein
      expression. HG also activated TGF-beta Smad2/3 signaling and activated
      extracellular signal-regulated kinase (ERK1/2) and p38 kinase signaling.
      Exogenous klotho (400 pM) attenuated HG-induced TGF-beta bioactivity, type II TGF
      beta receptor (TGF-betaRII) protein expression and TGF-beta Smad2/3 signaling.
      Klotho also attenuated HG-activated ERK1/2 and p38 kinase. Additionally, klotho
      and inhibitors of ERK1/2 or p38 kinase attenuated HG-induced fibronectin and cell
      hypertrophy. Finally, renal tubular expression of klotho decreased in the
      streptozotin-diabetic rats at 8 weeks. Thus, exogenous klotho attenuates HG
      induced profibrotic genes, TGF-beta signaling and cell hypertrophy in NRK-49F
      cells. Moreover, klotho attenuates HG-induced fibronectin expression and cell
      hypertrophy via the ERK1/2 and p38 kinase-dependent pathways.

PMID- 24721636
TI  - TGF-beta1 induces differentiation of papillary fibroblasts to reticular
      fibroblasts in monolayer culture but not in human skin equivalents.
AB  - Fibroblasts isolated from the papillary and reticular dermis are different from
      each other in vitro. If papillary fibroblasts are subjected to prolonged serial
      passaging they will differentiate into reticular fibroblasts. Reticular
      fibroblasts have been shown to resemble myofibroblasts in several ways. TGF-beta1
      is the most important factor involved in myofibroblast differentiation. AIMS: we
      investigated if TGF-beta1 can induce differentiation of papillary fibroblasts
      into reticular fibroblasts, in monolayer cultures and in human skin equivalents.
      METHOD: Monolayer cultures of and human skin equivalents generated with papillary
      fibroblasts were stimulated with TGF-beta1. The expression of markers specific
      for reticular and papillary fibroblasts was measured by qPCR and
      immunohistochemical analysis in monolayer cultures. In human skin equivalents,
      the morphology and the expression of several markers was analysed and compared to
      untreated papillary and reticular human skin equivalents. RESULTS: Monolayer
      cultures of papillary fibroblasts started to express a reticular marker profile
      after stimulation with TGF-beta1. Human skin equivalents generated with papillary
      fibroblast and stimulated with TGF-beta1 were similar to papillary control
      equivalents and did not obtain reticular characteristics. Expression of reticular
      markers was only found in the lower layers of TGF-beta1-stimulated papillary skin
      equivalents. CONCLUSIONS: TGF-beta1 can induce differentiation to reticular
      fibroblasts in monolayer cultures of papillary fibroblasts. In skin equivalents
      no such effects were found. The major difference between these experiments is the
      presence of extracellular matrix in skin equivalents. Therefore, we hypothesize
      that the matrix secreted by papillary fibroblasts protects them from TGF-beta1
      induced differentiation.

PMID- 24721637
TI  - The effect of tinted soft contact lens wear on functional visual acuity and
      higher-order aberrations.
AB  - PURPOSE: To investigate the differences of functional visual acuity (FVA) and
      high order aberrations (HOAs) in relation to tinted and clear hydrogel soft
      contact lens (SCL) wear. METHODS: A prospective comparative study was performed
      in 16 eyes of 16 healthy volunteers. Dynamic visual acuity (using a FVA
      measurement system) and higher-order aberrations (using a wavefront sensor) were
      compared in subjects wearing two types of soft contact lenses: 1-day Acuvue((r))
      (Vistakon, Jacksonville, FL) clear and the 1-day Acuvue((r)) Define(TM)
      (Vistakon, Jacksonville, FL) tinted lens. The blink rates were recorded during
      FVA testing. The correlation between the difference of HOAs and differences in
      FVA values was analyzed. RESULTS: The mean LogMAR FVA scores with clear and
      tinted SCLs were 0.07 +/- 0.13 and 0.14 +/- 0.17 (P<0.05). The mean blink
      frequencies with clear and tinted SCL wear were 18.4 +/- 8.3 and 25.3 +/- 4.7
      blinks/min (P<0.05). Both 3rd-order aberrations and total HOAs showed
      statistically significant differences between the two types of soft contact
      lenses for 6mm pupil measurements (P<0.05). A significant positive linear
      correlation was observed between DeltaHOAs and DeltaLogMAR FVA for 6mm pupil
      measurements (R=0.53, P=0.04). CONCLUSIONS: Tinted contact lens wear appears to
      induce a reduction in optical quality. Functional visual acuity measurement is a
      useful procedure to study the changes of visual performance and quality in tinted
      contact lens wear.

PMID- 24721635
TI  - Activation of the MKL1/actin signaling pathway induces hormonal escape in
      estrogen-responsive breast cancer cell lines.
AB  - Estrogen receptor alpha (ERalpha) is generally considered to be a good prognostic
      marker because almost 70% of ERalpha-positive tumors respond to anti-hormone
      therapies. Unfortunately, during cancer progression, mammary tumors can escape
      from estrogen control, resulting in resistance to treatment. In this study, we
      demonstrate that activation of the actin/megakaryoblastic leukemia 1 (MKL1)
      signaling pathway promotes the hormonal escape of estrogen-sensitive breast
      cancer cell lines. The actin/MKL1 signaling pathway is silenced in differentiated
      ERalpha-positive breast cancer MCF-7 and T47D cell lines and active in ERalpha
      negative HMT-3522 T4-2 and MDA-MB-231 breast cancer cells, which have undergone
      epithelial-mesenchymal transition. We showed that MKL1 activation in MCF-7 cells,
      either by modulating actin dynamics or using MKL1 mutants, down-regulates ERalpha
      expression and abolishes E2-dependent cell growth. Interestingly, the
      constitutively active form of MKL1 represses PR and HER2 expression in these
      cells and increases the expression of HB-EGF, TGFbeta, and amphiregulin growth
      factors in an E2-independent manner. The resulting expression profile (ER-, PR-,
      HER2-) typically corresponds to the triple-negative breast cancer expression
      profile. 

PMID- 24721638
TI  - Treatment of toxic metal aqueous solutions: encapsulation in a phosphate-calcium
      aluminate matrix.
AB  - Polyphosphate-modified calcium aluminate cement matrices were prepared by using
      aqueous solutions polluted with toxic metals as mixing water to obtain waste
      containing solid blocks with improved management and disposal. Synthetically
      contaminated waters containing either Pb or Cu or Zn were incorporated into
      phosphoaluminate cement mortars and the effects of the metal's presence on
      setting time and mechanical performance were assessed. Sorption and leaching
      tests were also executed and both retention and release patterns were
      investigated. For all three metals, high uptake capacities as well as percentages
      of retention larger than 99.9% were measured. Both Pb and Cu were seen to be
      largely compatible with this cementitious matrix, rendering the obtained blocks
      suitable for landfilling or for building purposes. However, Zn spoilt the
      compressive strength values because of its reaction with hydrogen phosphate
      anions, hindering the development of the binding matrix.

PMID- 24721639
TI  - Comparing analytic performance criteria: evaluation of HbA1c certification
      criteria as an example.
AB  - BACKGROUND: Direct comparison of analytical performance criteria that utilize
      different statistical approaches can be problematic. We describe a mathematical
      approach to compare performance criteria for hemoglobin A1c (HbA1c) analysis used
      by the NGSP standardization program and the College of American Pathologists
      (CAP) to enhance consistency between the schemes. METHODS: The imprecision (CV)
      and bias combinations required to pass each criterion at probabilities of 0.95,
      0.99 and 0.999 were calculated and used to construct contour plots to compare
      them. The CV/bias requirements were calculated mathematically for the 2011-2012
      CAP (3/3 results within +/-7% of the target) and different proposed NGSP (33/40
      to 40/40 results within +/-7% of the target) criteria, and using computer
      simulations for the existing NGSP criterion (95% confidence interval of the
      differences between the method and NGSP within +/-0.75% HbA1c). RESULTS:
      Requiring 37 of 40 results to be within +/-7% of the NGSP target best matched the
      CAP criterion at zero bias (95% chance of passing). CONCLUSIONS: The NGSP
      Steering Committee recommended a certification criterion of 37 of 40 results
      within +/-7% of the NGSP (reduced to +/-6% in 2014). The described evaluation
      approach may be useful in other situations where comparison of different
      performance criteria is desired.

PMID- 24721640
TI  - Plasma apelin: A novel biomarker for predicting diabetes.
AB  - BACKGROUND: Apelin regulates insulin sensitivity and secretion in animals.
      However, whether plasma apelin predicts incident diabetes in humans remains
      unknown. METHODS: We studied a cohort including 447 subjects (148 men, 299 women)
      without diabetes and followed for an average of 3y. Diabetes was diagnosed by an
      oral glucose tolerance test, plasma hemoglobin A1c, and if the subject was taking
      medications for diabetes. Plasma apelin-12 at baseline was measured with a
      commercial kit. RESULTS: Plasma apelin concentrations were higher in women than
      in men at baseline (p=0.007). During follow-up, 43 subjects developed type 2
      diabetes. Higher plasma apelin concentrations were associated with a higher risk
      of diabetes in men (p=0.049) but not in women. Plasma apelin predicted incident
      type 2 diabetes in men (hazard ratio, 2.13, 95% CI 1.29-3.51, p<0.05), but not in
      women, adjusted for age, family history of diabetes, hemoglobin A1c, body mass
      index, hypertension, and HOMA2-IR. Apelin could improve the prediction ability
      beyond traditional risk factors in men, and the sensitivity and specificity of
      plasma apelin at 0.9ng/ml for this prediction were 63.2% and 58.9%, respectively.
      In men at risk for diabetes (HbA1c 5.7-6.4%, FPG 100-125mg/dl, or OGTT-2h-PG 140
      199mg/dl), the risk for developing diabetes was higher in those with higher
      plasma apelin concentration than in those with lower plasma apelin concentrations
      (10.6%/year vs. 5.1%/year, p<0.001). CONCLUSIONS: Plasma apelin is a novel
      biomarker for predicting type 2 diabetes in men.

PMID- 24721641
TI  - Matrix metalloproteinases in pneumonia.
AB  - Pneumonia is a worldwide infectious disease that is associated with significant
      morbidity and mortality and is the most common fatal infection acquired in
      hospitals. Despite advances in preventive strategies, such as antibiotic
      therapies and intensive care, the mortality rate still requires substantial
      improvement. Matrix metalloproteinases (MMPs) are a large family of zinc
      dependent endopeptidases, which are known as the major enzymes responsible for
      the proteolytic degradation of proteinaceous components of the extracellular
      matrix (ECM). Although the main function of MMPs is the removal of the ECM during
      tissue resorption and progression of various diseases, MMPs also interact with
      multiple cytokines, participating in the pathology of infection and inflammation.
      This review presents a schematic overview of the different MMPs expressed in
      pneumonia. MMPs are key factors in the pathogenesis of various types of
      pneumonia, such as community-acquired pneumonia, hospital-acquired pneumonia, and
      ventilator-associated pneumonia. Here, we review the pathological roles of
      various MMPs in pneumonia. 

PMID- 24721642
TI  - Evaluation of a new NGS method based on a custom AmpliSeq library and Ion Torrent
      PGM sequencing for the fast detection of genetic variations in cardiomyopathies.
AB  - BACKGROUND: Hypertrophic and dilated cardiomyopathies are common genetic cardiac
      diseases. Due to large cohorts to investigate, large number of causative genes
      and high rate of private mutations, mutational screening must be performed using
      an extremely sensitive and specific detection method. METHODS: NGS workflow based
      on a custom AmpliSeq panel was designed for sequencing most prevalent
      cardiomyopathy-causing genes on the Ion PGMTM Sequencer. A cohort of 75
      previously studied patients was screened to evaluate this strategy in terms of
      sensibility, specificity, practicability and cost. In silico analysis was
      performed using the NextGENe(r) software. RESULTS: Our AmpliSeq custom panel
      allowed us to efficiently explore 96% of targeted sequences. Using adjusted
      alignment settings, all genetic variants (57 substitutions, 34 indels) present in
      covered regions and previously detected by HRM/sequencing were readily identified
      except a 73-bp MYBPC3 deletion (analytical sensitivity: 98.9%). Uncovered
      targeted regions were further analysed by a HRM/sequencing strategy. Complete
      molecular investigation was performed faster and cheaper than with previously
      used mutation detection methods. CONCLUSION: Finally, these results suggested
      that our new NGS approach based on Ampliseq libraries and Ion PGM sequencing is a
      highly efficient, fast and cheap high-throughput mutation detection method that
      is ready to be deployed in clinical laboratories.

PMID- 24721643
TI  - The storage stability and concentration of acetoacetate differs between blood
      fractions.
AB  - BACKGROUND: Plasma concentrations of 3-hydroxybutyrate (3HB) are measured more
      often than acetoacetate (AcAc) which may be due to the reported storage
      instability of AcAc. The aims of the study were to compare the storage stability
      of AcAc in different blood fractions over time (90days) when stored at -80
      degrees C and to determine the postprandial concentration of AcAc in whole blood,
      plasma and red blood cells. METHODS: Blood was collected from fasting subjects
      (n=5): whole blood, plasma and red blood cells were isolated and deproteinised in
      perchloric acid, and supernatants were stored at -80 degrees C until analysis.
      Postprandial concentrations of AcAc in whole blood, plasma and red blood cells
      were determined at regular intervals over 420min, after subjects (n=23) had
      consumed a mixed test meal. RESULTS: Storing deproteinised plasma at -80 degrees
      C resulted in no significant change in AcAc concentration over 60days. In
      contrast, whole blood AcAc concentrations significantly decreased by 51%
      (p=0.018) within 30days. The concentration of AcAc in fasting and postprandial
      plasma was notably higher than that of whole blood and red blood cells.
      DISCUSSION: Our data demonstrates that plasma for AcAc analysis can be stored for
      longer than previously suggested provided that plasma is deproteinised and stored
      at -80 degrees C.

PMID- 24721644
TI  - Whole-genome sequencing of six dog breeds from continuous altitudes reveals
      adaptation to high-altitude hypoxia.
AB  - The hypoxic environment imposes severe selective pressure on species living at
      high altitude. To understand the genetic bases of adaptation to high altitude in
      dogs, we performed whole-genome sequencing of 60 dogs including five breeds
      living at continuous altitudes along the Tibetan Plateau from 800 to 5100 m as
      well as one European breed. More than 150* sequencing coverage for each breed
      provides us with a comprehensive assessment of the genetic polymorphisms of the
      dogs, including Tibetan Mastiffs. Comparison of the breeds from different
      altitudes reveals strong signals of population differentiation at the locus of
      hypoxia-related genes including endothelial Per-Arnt-Sim (PAS) domain protein 1
      (EPAS1) and beta hemoglobin cluster. Notably, four novel nonsynonymous mutations
      specific to high-altitude dogs are identified at EPAS1, one of which occurred at
      a quite conserved site in the PAS domain. The association testing between EPAS1
      genotypes and blood-related phenotypes on additional high-altitude dogs reveals
      that the homozygous mutation is associated with decreased blood flow resistance,
      which may help to improve hemorheologic fitness. Interestingly, EPAS1 was also
      identified as a selective target in Tibetan highlanders, though no amino acid
      changes were found. Thus, our results not only indicate parallel evolution of
      humans and dogs in adaptation to high-altitude hypoxia, but also provide a new
      opportunity to study the role of EPAS1 in the adaptive processes. 

PMID- 24721645
TI  - Blood mRNA expression profiling predicts survival in patients treated with
      tremelimumab.
AB  - PURPOSE: Tremelimumab (ticilimumab, Pfizer), is a monoclonal antibody (mAb)
      targeting cytotoxic T lymphocyte-associated antigen-4 (CTLA-4). Ipilimumab
      (Yervoy, BMS), another anti-CTLA-4 antibody, is approved by the U.S. Federal Drug
      Administration (FDA). Biomarkers are needed to identify the subset of patients
      who will achieve tumor control with CTLA-4 blockade. EXPERIMENTAL DESIGN:
      Pretreatment peripheral blood samples from 218 patients with melanoma who were
      refractory to prior therapy and receiving tremelimumab in a multicenter phase II
      study were measured for 169 mRNA transcripts using reverse transcription
      polymerase chain reaction (RT-PCR). A two-class latent model yielded a risk score
      based on four genes that were highly predictive of survival (P < 0.001). This
      signature was validated in an independent population of 260 treatment-naive
      patients with melanoma enrolled in a multicenter phase III study of tremelimumab.
      RESULTS: Median follow-up was 297 days for the training population and 386 days
      for the test population. Expression levels of the 169 genes were closely
      correlated across the two populations (r = 0.9939). A four-gene model, including
      cathepsin D (CTSD), phopholipase A2 group VII (PLA2G7), thioredoxin reductase 1
      (TXNRD1), and interleukin 1 receptor-associated kinase 3 (IRAK3), predicted
      survival in the test population (P = 0.001 by log-rank test). This four-gene
      model added to the predictive value of clinical predictors (P < 0.0001).
      CONCLUSIONS: Expression levels of CTSD, PLA2G7, TXNRD1, and IRAK3 in peripheral
      blood are predictive of survival in patients with melanoma treated with
      tremelimumab. Blood mRNA signatures should be further explored to define patient
      subsets likely to benefit from immunotherapy.

PMID- 24721646
TI  - Autophagy inhibition augments the anticancer effects of epirubicin treatment in
      anthracycline-sensitive and -resistant triple-negative breast cancer.
AB  - PURPOSE: Triple-negative breast cancers (TNBC) are defined by a lack of
      expression of estrogen receptor (ER), progesterone receptor (PR), and human
      epidermal growth factor receptor 2 (ERBB2/HER2). Although initially responsive to
      chemotherapy, most recurrent TNBCs develop resistance, resulting in disease
      progression. Autophagy is a lysosome-mediated degradation and recycling process
      that can function as an adaptive survival response during chemotherapy and
      contribute to chemoresistance. Our goal was to determine whether autophagy
      inhibition improves treatment efficacy in TNBC cells in tumors either sensitive
      or refractory to anthracyclines. EXPERIMENTAL DESIGN: We used in vitro and in
      vivo models of TNBC using cell lines sensitive to epirubicin and other
      anthracyclines, as well as derivative lines, resistant to the same drugs. We
      assessed basal autophagy levels and the effects of chemotherapy on autophagy in
      parental and resistant cells. Applying various approaches to inhibit autophagy
      alone and in combination with chemotherapy, we assessed the effects on cell
      viability in vitro and tumor growth rates in vivo. RESULTS: We demonstrated that
      epirubicin induced autophagic flux in TNBC cells. Epirubicin-resistant lines
      exhibited at least 1.5-fold increased basal autophagy levels and, when treated
      with autophagy inhibitors, showed a significant loss in viability, indicating
      dependence of resistant cells on autophagy for survival. Combination of
      epirubicin with the autophagy inhibitor hydroxychloroquine resulted in a
      significant reduction in tumor growth compared with monotherapy with epirubicin.
      CONCLUSION: Autophagy inhibition enhances therapeutic response in both
      anthracycline-sensitive and -resistant TNBC and may be an effective new treatment
      strategy for this disease.

PMID- 24721647
TI  - Targeting the inward-rectifier potassium channel ROMK in cardiovascular disease.
AB  - The kidney plays a critical role in blood pressure homeostasis as a result of the
      integrated activity of different mechanisms that ensure proper salt and water
      reabsorption. Diuretics, developed more than four decades ago, are used to treat
      hypertension and/or congestive heart failure, although there are therapeutic
      issues that limit their use. Human and rodent genetic studies provide a large
      body of evidence which suggests that inhibitors of the kidney potassium channel,
      ROMK, will represent novel diuretics for the treatment of hypertension. The
      search for potent and selective ROMK inhibitors has recently yielded compounds
      that display efficacy in animal models, providing the first pharmacological
      validation of ROMK as a novel diuretic target. 

PMID- 24721648
TI  - Cardiac and renal inward rectifier potassium channel pharmacology: emerging tools
      for integrative physiology and therapeutics.
AB  - Inward rectifier potassium (Kir) channels play fundamental roles in cardiac and
      renal function and may represent unexploited drug targets for cardiovascular
      diseases. However, the limited pharmacology of Kir channels has slowed progress
      toward exploring their integrative physiology and therapeutic potential. Here, we
      review recent progress toward developing the small-molecule pharmacology for
      Kir2.x, Kir4.1, and Kir7.1 and discuss common mechanistic themes that may help
      guide future Kir channel-directed drug discovery efforts. 

PMID- 24721649
TI  - Cardiac safety assays.
AB  - Cardiac safety, including the risk of drug-induced 'torsades de pointes' (TdP)
      arrhythmia, is a major concern in the development, approval and prescription of
      new drugs. Assessment of surrogate markers of TdP-risk, such as QT-interval
      prolongation or inhibition of the rapid delayed-rectifier K(+)-current (IKr)
      encoded by the human ether-a-go-go-related gene (hERG), is therefore required
      before drug approval. Here, we review some methodologies employed to assess
      proarrhythmia liability of drugs, discuss the challenges involved in this
      process, and highlight promising novel cardiac-safety assays. 

PMID- 24721650
TI  - HERG1 channel agonists and cardiac arrhythmia.
AB  - Type 1 human ether-a-go-go-related gene (hERG1) potassium channels are a key
      determinant of normal repolarization of cardiac action potentials. Loss of
      function mutations in hERG1 channels cause inherited long QT syndrome and
      increased risk of cardiac arrhythmia and sudden death. Many common medications
      that block hERG1 channels as an unintended side effect also increase arrhythmic
      risk. Routine preclinical screening for hERG1 block led to the discovery of
      agonists that shorten action potential duration and QT interval. Agonists have
      the potential to be used as pharmacotherapy for long QT syndrome, but can also be
      proarrhythmic. Recent studies have elucidated multiple mechanisms of action for
      these compounds and the structural basis for their binding to the pore domain of
      the hERG1 channel. 

PMID- 24721651
TI  - Interacting influence of diuretics and diet on BK channel-regulated K
      homeostasis.
AB  - Large conductance, Ca-activated K channels (BK) are abundantly located in cells
      of vasculature, glomerulus, and distal nephron, where they are involved in
      maintaining blood volume, blood pressure, and K homeostasis. In mesangial cells
      and smooth muscle cells of vessels, the BK-alpha pore associates with BK-beta1
      subunits and regulates contraction in a Ca-mediated feedback manner. The BK-beta1
      also resides in connecting tubule cells of the nephron. BK-beta1 knockout mice
      (beta1KO) exhibit fluid retention, hypertension, and compromised K handling. The
      BK-alpha/beta4 resides in acid/base transporting intercalated cells (IC) of the
      distal nephron, where they mediate K secretion in mammals on a high K, alkaline
      diet. BK-alpha expression in IC is increased by a high K diet via aldosterone.
      The BK-beta4 subunit and alkaline urine are necessary for the luminal expression
      and function of BK-alpha in mouse IC. In distal nephron cells, membrane BK-alpha
      expression is inhibited by WNK4 in in vitro expression systems, indicating a role
      in the hyperkalemic phenotype in patients with familial hyperkalemic hypertension
      type 2 (FHHt2). beta1KO and BK-beta4 knockout mice (beta4KO) are hypertensive
      because of exaggerated epithelial Na channels (ENaC) mediated Na retention in an
      effort to secrete K via only renal outer medullary K channels (ROMK). BK
      hypertension is resistant to thiazides and furosemide, and would be more amenable
      to ENaC and aldosterone inhibiting drugs. Activators of BK-alpha/beta1 or BK
      alpha/beta4 might be effective blood pressure lowering agents for a subset of
      hypertensive patients. Inhibitors of renal BK would effectively spare K in
      patients with Bartter Syndrome, a renal K wasting disease. 

PMID- 24721652
TI  - Epithelial sodium channel (ENaC) and the control of blood pressure.
AB  - The amiloride-sensitive epithelial sodium channel (ENaC) constitutes the rate
      limiting step for sodium reabsorption in epithelial cells that line the distal
      part of the renal tubule, the distal colon, the duct of several exocrine glands,
      and the lung. The activity of this channel is regulated by aldosterone and
      hormones involved in the maintenance of sodium balance, blood volume and blood
      pressure. In this review, we discuss recent advances in our understanding of ENaC
      function and regulation relevant to the control of sodium balance and blood
      pressure. The identification of novel drug targets should help in the development
      of the next generation of diuretics and of new therapies for the treatment of
      hypertension. 

PMID- 24721654
TI  - Targeting sodium channels in cardiac arrhythmia.
AB  - Cardiac voltage-gated sodium channels are responsible for proper electrical
      conduction in the heart. During acquired pathological conditions and inherited
      sodium channelopathies, altered sodium channel function causes conduction
      disturbances and ventricular arrhythmias. Although the clinical, genetic and
      biophysical characteristics of cardiac sodium channel disease have been
      extensively studied, limited progress has been made in the development of
      treatment strategies targeting sodium channels. Classical non-selective sodium
      channel blockers have only limited clinical applicability, while more selective
      inhibitors of the late sodium current constitute a more promising treatment
      option. Because of our insufficient understanding of their complexity and
      subcellular diversity, other specific therapeutic targets for modulating sodium
      channels remain elusive. The current status and future potential of targeting
      sodium channels in cardiac arrhythmias are discussed. 

PMID- 24721653
TI  - Recent genetic discoveries implicating ion channels in human cardiovascular
      diseases.
AB  - The term 'channelopathy' refers to human genetic disorders caused by mutations in
      genes encoding ion channels or their interacting proteins. Recent advances in
      this field have been enabled by next-generation DNA sequencing strategies such as
      whole exome sequencing with several intriguing and unexpected discoveries. This
      review highlights important discoveries implicating ion channels or ion channel
      modulators in cardiovascular disorders including cardiac arrhythmia
      susceptibility, cardiac conduction phenotypes, pulmonary and systemic
      hypertension. These recent discoveries further emphasize the importance of ion
      channels in the pathophysiology of human disease and as important druggable
      targets. 

PMID- 24721656
TI  - TRPM4 channels in the cardiovascular system.
AB  - The non-selective Transient Receptor Potential Melastatin 4 (TRPM4) cation
      channel is abundantly expressed in cardiac cells, being involved in several
      aspects of cardiac rhythmicity, including cardiac conduction, pace making and
      action-potential repolarization. Dominantly inherited mutations in the TRPM4 gene
      are associated with the cardiac bundle-branch disorder progressive familial heart
      block type I (PFHBI) and isolated cardiac conduction disease (ICCD) giving rise
      to atrio-ventricular conduction block (AVB), right bundle branch block,
      bradycardia, and the Brugada syndrome. The mutant phenotypes closely resemble
      those associated with mutations in the SCN5A gene, encoding the voltage-gated
      Na(+) channel NaV1.5. These observations and the unexpected partnership with
      sulfonylurea-receptors (SURs) makes the TRPM4 channel a promising novel target
      for treatment of cardiac disorders. 

PMID- 24721655
TI  - Personalized medicine to treat arrhythmias.
AB  - The efficacy of antiarrhythmic drug therapy is incomplete, with responses ranging
      from efficacy to no effect to severe adverse effects, including paradoxical drug
      induced arrhythmia. Most antiarrhythmic drugs were developed at a time when the
      mechanisms underlying arrhythmias were not well understood. In the last decade, a
      range of experimental approaches have advanced our understanding of the molecular
      and genomic contributors to the generation of an arrhythmia-prone heart, and this
      information is directly informing targeted therapy with existing drugs or the
      development of new ones. The development of inexpensive whole genome sequencing
      holds the promise of identifying patients susceptible to arrhythmias in a
      presymptomatic phase, and thus implementing preventive therapies. 

PMID- 24721657
TI  - Recent molecular insights from mutated IKS channels in cardiac arrhythmia.
AB  - Co-assembly of KCNQ1 with KCNE1 generates the IKS potassium current that is vital
      for the proper repolarization of the cardiac action potential. Mutations in
      either KCNQ1 or KCNE1 genes lead to life-threatening cardiac arrhythmias causing
      long QT syndrome, short QT syndrome, sinus bradycardia and atrial fibrillation.
      Findings emerging from recent studies are beginning to provide a picture of how
      gain-of-function and loss-of-function mutations are associated with pleiotropic
      cardiac phenotypes in the clinics. In this review, we discuss recent molecular
      insights obtained from mutations altering different structural modules of the
      channel complex that are essential for proper IKS function. We present the
      possible molecular mechanisms underlying mutations impairing the voltage sensing
      functions, as well as those altering the channel regulation by
      phosphatidylinositol-4,5-bisphosphate, calmodulin and protein kinase A. We also
      discuss the significance of diseased IKS channels for adequate pharmacological
      targeting of cardiac arrhythmias. 

PMID- 24721658
TI  - Computer-supported diagnosis for endotension cases in endovascular aortic
      aneurysm repair evolution.
AB  - An abdominal aortic aneurysm (AAA) is a localized abnormal enlargement of the
      abdominal aorta with fatal consequences if not treated on time. The endovascular
      aneurysm repair (EVAR) is a minimal invasive therapy that reduces recovery times
      and improves survival rates in AAA cases. Nevertheless, post-operation
      difficulties can appear influencing the evolution of treatment. The objective of
      this work is to develop a pilot computer-supported diagnosis system for an
      automated characterization of EVAR progression from CTA images. The system is
      based on the extraction of texture features from post-EVAR thrombus aneurysm
      samples and on posterior classification. Three conventional texture-analysis
      methods, namely the gray level co-occurrence matrix (GLCM), the gray level run
      length matrix (GLRLM), the gray level difference method (GLDM), and a new method
      proposed by the authors, the run length matrix of local co-occurrence matrices
      (RLMLCM), were applied to each sample. Several classification schemes were
      experimentally evaluated. The ensembles of a k-nearest neighbor (k-NN), a
      multilayer perceptron neural network (MLP-NN), and a support vector machine (SVM)
      classifier fed with a reduced version of texture features resulted in a better
      performance (Az=94.35+/-0.30), as compared to the classification performance of
      the other alternatives. 

PMID- 24721660
TI  - Perioperative measures to optimize margin clearance in breast conserving surgery.
AB  - Margin status is one of the most important determinants of local recurrence
      following breast conserving surgery. The fact that up to 60% of patients
      undergoing breast conserving surgery require re-excision highlights the
      importance of optimizing margin clearance. In this review we summarize the
      following perioperative measures that aim to enhance margin clearance: (1)
      patient risk stratification, specifically risk factors and nomograms, (2)
      preoperative imaging, (3) intraoperative techniques including wire-guided
      localization, radioguided surgery, intraoperative ultrasound-guided resection,
      intraoperative specimen radiography, standardized cavity shaving, and ink
      directed focal re-excision; (4) and intraoperative pathology assessment
      techniques, namely frozen section analysis and imprint cytology. Novel surgical
      techniques as well as emerging technologies are also reviewed. Effective
      treatment requires accurate preoperative planning, developing and implementing a
      consistent definition of margin clearance, and using tools that provide detailed
      real-time intraoperative information on margin status. 

PMID- 24721659
TI  - Pretreatment with Saccharomyces boulardii does not prevent the experimental
      mucositis in Swiss mice.
AB  - BACKGROUND: The antimetabolite chemotherapy 5-Fluorouracil is one of the most
      commonly prescribed drugs in clinical cancer treatment. Although this drug is not
      specific for cancer cells and also acts on healthy cells, it can cause mucositis,
      a common collateral effect. Dysbiosis has also been described in 5-fluorouracil
      induced mucositis and is likely to contribute to the overall development of
      mucositis. In light of this theory, the use of probiotics could be a helpful
      strategy to alleviate mucositis. So the aim of this study was evaluate the impact
      of the probiotic Saccharomyces boulardii in a model of mucositis. RESULTS: After
      induced of mucositis, mice from the Mucositis groups showed a decrease in food
      consumption (p < 0.05) and therefore had a greater weight loss (p < 0.05). The
      treatment with Saccharomyces boulardii did not reverse this effect (p > 0.05).
      Mucositis induced an increase in intestinal permeability and intestinal
      inflammation (p < 0.05). There were no differences in mucosal lesions, intestinal
      permeability and sIgA secretion (p > 0.05) in mice pretreated with S. boulardii.
      CONCLUSIONS: S. boulardii was not able to prevent the effects of experimental
      mucositis induced by 5- Fluorouracil.

PMID- 24721661
TI  - Intraperitoneal chemotherapy against peritoneal carcinomatosis: current status
      and future perspective.
AB  - Peritoneal carcinomatosis (PC), caused by advanced abdominal malignancies, such
      as those of the ovarian and gastrointestinal tracts, has an extremely poor
      prognosis. Intraperitoneal (IP) chemotherapy has been clinically applied for
      several decades, but its clinical efficacy has not been fully determined. An
      accumulating body of evidence suggests that cytoreductive surgery (CRS) plus
      hyperthermic intraperitoneal chemotherapy (HIPEC) is the optimal treatment for
      selected patients with ovarian and colorectal cancers with PC. Recent studies
      suggest that IP administration of taxane with systemic chemotherapy in a
      neoadjuvant setting improves patient survival in gastric cancer with PC. The
      pharmacokinetics of IP-administered drugs should be primarily considered in order
      to optimize IP chemotherapy. Therefore, the development of specific IP drugs
      using newly emerging molecular targeted reagents or new drug delivery systems,
      such as nanomedicine or controlled absorption/release methods, is essential to
      improve the efficacy of IP chemotherapy. 

PMID- 24721662
TI  - Structure, composition, and strength of nitrifying membrane-aerated biofilms.
AB  - Membrane-aerated biofilm reactors (MABRs) are a novel technology based on the
      growth of biofilms on oxygen-permeable membranes. Hereby, MABRs combine all the
      advantages of biofilm growth with a more flexible and efficient control of the
      oxygen load. In the present work, MABR flow cells were operated to achieve full
      nitrification. MABR biofilms had a significantly different structure than co
      diffusion biofilms reported in the literature. Different levels of shear stress
      and oxygen loading during MABR operation also affected the biofilm parameters.
      Furthermore, reactor operation at higher oxygen loads resulted in an increased
      biofilm cohesiveness, which depended on the EPS mass in the biofilms and the type
      of stress applied (more cohesive against normal than shear stresses). The EPS in
      the strongest biofilms had a higher content of proteins and a lower level of
      carbohydrates. Staining analyses revealed that the outermost EPS in the stronger
      biofilm regions was of hydrophilic nature and distributed around dense microbial
      aggregates, whereas it was homogeneously distributed in the weaker strata.
      Overall, the obtained results provide input parameters to future modelling
      efforts and operating conditions to support more robust autotrophic N conversions
      in MABRs. 

PMID- 24721664
TI  - Membrane scaling and flux decline during fertiliser-drawn forward osmosis
      desalination of brackish groundwater.
AB  - Fertiliser-drawn forward osmosis (FDFO) desalination has been recently studied as
      one feasible application of forward osmosis (FO) for irrigation. In this study,
      the potential of membrane scaling in the FDFO process has been investigated
      during the desalination of brackish groundwater (BGW). While most fertilisers
      containing monovalent ions did not result in any scaling when used as an FO draw
      solution (DS), diammonium phosphate (DAP or (NH4)2HPO4) resulted in significant
      scaling, which contributed to severe flux decline. Membrane autopsy using
      scanning electron microscopy (SEM), energy-dispersive x-ray spectroscopy (EDS),
      and x-ray diffraction (XRD) analysis indicated that the reverse diffusion of DAP
      from the DS to the feed solution was primarily responsible for scale formation
      during the FDFO process. Physical cleaning of the membrane with deionised water
      at varying crossflow velocities was employed to evaluate the reversibility of
      membrane scaling and the extent of flux recovery. For the membrane scaled using
      DAP as DS, 80-90% of the original flux was recovered when the crossflow velocity
      for physical cleaning was the same as the crossflow velocity during FDFO
      desalination. However, when a higher crossflow velocity or Reynolds number was
      used, the flux was recovered almost completely, irrespective of the DS
      concentration used. This study underscores the importance of selecting a suitable
      fertiliser for FDFO desalination of brackish groundwater to avoid membrane
      scaling and severe flux decline. 

PMID- 24721663
TI  - Control of aeration, aerobic SRT and COD input for mainstream
      nitritation/denitritation.
AB  - This work describes the development of an intermittently aerated pilot-scale
      process (V = 0.34 m(3)) operated without oxidized nitrogen recycle and
      supplemental carbon addition optimized for nitrogen removal via
      nitritation/denitritation. The aeration pattern was controlled using a novel
      aeration strategy based on set-points for reactor ammonia, nitrite and nitrate
      concentrations with the aim of maintaining equal effluent ammonia and nitrate +
      nitrite (NOx) concentrations. Further, unique operational and process control
      strategies were developed to facilitate the out-selection of nitrite oxidizing
      bacteria (NOB) based on optimizing the chemical oxygen demand (COD) input,
      imposing transient anoxia, aggressive solids retention time (SRT) operation
      towards ammonia oxidizing bacteria (AOB) washout and high dissolved oxygen (DO)
      (>1.5 mg/L). Sustained nitrite accumulation (NO2-N/NOx-N = 0.36 +/- 0.27) was
      observed while AOB activity was greater than NOB activity (AOB: 391 +/- 124
      mgN/L/d, NOB: 233 +/- 151 mgN/L/d, p < 0.001) during the entire study. The
      reactor demonstrated total inorganic nitrogen (TIN) removal rate of 151 +/- 74
      mgN/L/d at an influent COD/ [Formula: see text] -N ratio of 10.4 +/- 1.9 at 25 
      degrees C. The TIN removal efficiency was 57  +/-  25% within the hydraulic
      retention time (HRT) of 3 h and within an SRT of 4-8 days. Therefore, this pilot
      scale study demonstrates that application of the proposed online aeration control
      is able to out-select NOB in mainstream conditions providing relatively high
      nitrogen removal without supplemental carbon and alkalinity at a low HRT. 

PMID- 24721666
TI  - Structural redundancy of data from wastewater treatment systems. Determination of
      individual balance equations.
AB  - Although data reconciliation is intensely applied in process engineering, almost
      none of its powerful methods are employed for validation of operational data from
      wastewater treatment plants. This is partly due to some prerequisites that are
      difficult to meet including steady state, known variances of process variables
      and absence of gross errors. However, an algorithm can be derived from the
      classical approaches to data reconciliation that allows to find a comprehensive
      set of equations describing redundancy in the data when measured and unmeasured
      variables (flows and concentrations) are defined. This is a precondition for
      methods of data validation based on individual mass balances such as CUSUM
      charts. The procedure can also be applied to verify the necessity of existing or
      additional measurements with respect to the improvement of the data's redundancy.
      Results are given for a large wastewater treatment plant. The introduction aims
      at establishing a link between methods known from data reconciliation in process
      engineering and their application in wastewater treatment. 

PMID- 24721665
TI  - Sunlight-induced transformation of sulfadiazine and sulfamethoxazole in surface
      waters and wastewater effluents.
AB  - Sulfadiazine (SD) and sulfamethoxazole (SMX) are widely used sulfonamide
      antibiotics, which are present as contaminants in surface waters and are known to
      undergo phototransformation. This kinetic study was conducted to identify the
      processes responsible for their phototransformation in sunlit surface waters.
      Water samples from the Thur River (Switzerland) and from a pilot wastewater
      treatment plant, as well as aqueous solutions of two well-characterized natural
      dissolved organic matter (DOM) extracts, namely Suwannee River and Pony Lake
      fulvic acids (SRFA, PLFA), were examined. Both sulfonamides were found to undergo
      direct and indirect phototransformation, with contributions of excited triplet
      states of DOM and of effluent organic matter (EfOM) and possibly of hydroxyl
      radical and other unidentified reactive species. Under simulated sunlight, SMX
      mainly reacted through direct phototransformation, with a certain contribution of
      indirect phototransformation occurring for a wastewater effluent. The behavior of
      SD was found to be more diverse. For river waters, wastewater effluents and PLFA
      solutions, indirect phototransformation was predominant, while for SRFA solutions
      direct phototransformation prevailed. The rates of phototransformation of SD were
      interpreted as the result of a complex interplay between the photosensitizing and
      the inhibitory effect of DOM/EfOM, with an additional component related to the
      nitrite ion as a source of photoproduced hydroxyl radical. For typical conditions
      found in surface waters comparable to the Thur River, phototransformation half
      lives on the order of 3-13 d were estimated for the two studied sulfonamides. 

PMID- 24721667
TI  - Translating removal efficiencies into operational performance indices of
      wastewater treatment plants.
AB  - Removal efficiencies are often used to assess the performance of a single or a
      group of unit operations/processes (UOPs) of a wastewater treatment plant (WWTP).
      However, depending on the influent concentration (Cin), the same efficiency of
      removal (Er) may be insufficient or excessive to achieve the UOP or WWTP effluent
      quality requirements, expressed by concentration limit values (LVs). This paper
      proposes performance indices (PXs), Er-based, as new metrics for benchmarking,
      i.e. for assessing and improving the performance of each UOP or treatment step
      and ultimately of the WWTP as a multi-barrier system, and comprehensively
      describes the stepwise method of translating Ers into PXs. PXs are dimensionless
      and vary between 0 and 300 to define three performance levels: unsatisfactory (0
      100), acceptable (100-200) and good (200-300) performance. The method developed
      takes into consideration Cin and LV, and the reference values for judging the
      performance are given from Er-Cin typical ranges and Er vs. Cin model curves, LV
      based and field data based. The general equations of the Er model curves are
      derived. A set of six curves is calibrated for TSS (Total Suspended Solids) and
      COD (Chemical Oxygen Demand) removal by primary sedimentation and activated
      sludge systems (carbon or combined carbon and nutrients removal), using 5-year
      (2006-2010) field data from five Portuguese WWTPs. A statistical analysis of the
      PX results is additionally proposed to assess treatment reliability. The new
      method is applied in two WWTPs and the PX results are compared with those of
      conventional measures - Er and performance indicators (PIs). The results
      demonstrate that, whereas a simplistic Er-driven or PI-driven management of the
      WWTPs shows limitations, the developed PXs are adequate measures for benchmarking
      removal efficiencies towards WWTP reliability and sustainability. 

PMID- 24721668
TI  - Prevalence and determinants of osteoporosis in patients with type 1 and type 2
      diabetes mellitus.
AB  - BACKGROUND: Increased risk of osteoporosis and its clinical significance in
      patients with diabetes is controversial. We analyze osteoporosis prevalence and
      determinants of bone mineral density (BMD) in patients with type 1 and 2
      diabetes. METHODS: Three hundred and ninety-eight consecutive diabetic patients
      from a single outpatient clinic received a standardized questionnaire on
      osteoporosis risk factors, and were evaluated for diabetes-related complications,
      HbA1c levels, and lumbar spine (LS) and femoral neck (FN) BMD. Of these, 139 (71
      men, 68 women) type 1 and 243 (115 men, 128 women) type 2 diabetes patients were
      included in the study. BMD (T-scores and values adjusted for age, BMI and
      duration of disease) was compared between patient groups and between patients
      with type 2 diabetes and population-based controls (255 men, 249 women). RESULTS:
      For both genders, adjusted BMD was not different between the type 1 and type 2
      diabetes groups but was higher in the type 2 group compared with controls (p <
      0.0001). Osteoporosis prevalence (BMD T-score < -2.5 SD) at FN and LS was
      equivalent in the type 1 and type 2 diabetes groups, but lower in type 2 patients
      compared with controls (FN: 13.0% vs 21.2%, LS: 6.1% vs 14.9% men; FN: 21.9% vs
      32.1%, LS: 9.4% vs 26.9% women). Osteoporosis prevalence was higher at FN-BMD
      than at LS-BMD. BMD was positively correlated with BMI and negatively correlated
      with age, but not correlated with diabetes-specific parameters (therapy, HbBA1c,
      micro- and macrovascular complications) in all subgroups. Fragility fracture
      prevalence was low (5.2%) and not different between diabetes groups. Fracture
      patients had lower BMDs compared with those without fractures; however, BMD T
      score was above -2.5 SD in most patients. CONCLUSIONS: Diabetes-specific
      parameters did not predict BMD. Fracture occurrence was similar in both diabetes
      groups and related to lower BMD, but seems unrelated to the threshold T-score, <
      2.5 SD. These results suggest that osteoporosis, and related fractures, is a
      clinically significant and commonly underestimated problem in diabetes patients.

PMID- 24721669
TI  - Effects of electrical lesions of the medial preoptic area and the ventral
      pallidum on mate-dependent paternal behavior in mice.
AB  - In laboratory animals, less is known about the neural circuits that mediate
      paternal behavior than those that influence maternal behavior. In mice, we
      recently reported that when sires are separated with their mate dams from their
      pups, ultrasound and pheromonal signals from the dams can evoke and initiate
      maternal-like retrieval behavior in the sires upon reunion with the offspring;
      this is termed mate-dependent paternal care. We used electrolytic brain lesion
      (EBL) methods to identify the potential roles of the medial preoptic area (mPOA)
      and ventral pallidum (VP) regions in regulating paternal care, areas known to be
      critical for the expression of maternal behavior. Electrolytic lesions of the
      mPOA or VP disrupted mate-dependent paternal care; latencies to initiate pup
      retrieval, grooming and crouching were longer in the EBL-treated sires relative
      to the sham-operated mice. The number of grooming episodes and duration of
      crouching were also lower in sires with the EBL in both areas. These results
      indicate that the mPOA and VP regions are essential for mate-dependent paternal
      care in mice. 

PMID- 24721670
TI  - Pyrosequencing analysis of SNCA methylation levels in leukocytes from Parkinson's
      disease patients.
AB  - DNA methylation of a CpG island located in intron 1 of the alpha-synuclein gene
      (SNCA) has been reported to play an essential role in the regulation of alpha
      synuclein transcription, and probably has a close association with Parkinson's
      disease (PD). However, there is no simple and cost effective method to quantify
      DNA methylation in this region. Additionally, whether this CpG island is
      hypomethylated in peripheral blood in PD and can be used as PD biomarker is still
      under debate. In the present study, we developed a set of bisulfite
      pyrosequencing assays which can be used to examine the DNA methylation level of
      13 CpG sites in intron 1 of SNCA. We compared DNA methylation levels at these
      sites in leukocytes from 50 PD patients and 50 healthy controls. Our results
      indicated that there were no significant differences in DNA methylation between
      PD patients and controls. 

PMID- 24721672
TI  - TDP-43 interaction with the intracellular domain of amyloid precursor protein
      induces p53-associated apoptosis.
AB  - TAR DNA-binding protein 43 (TDP-43), an essential pathological protein in both
      amyotrophic later sclerosis (ALS) and frontotemporal lobar degeneration (FTLD),
      is expressed abnormally in Alzheimer's disease (AD). However, whether and how TDP
      43 contributes the pathogenesis of AD remains unknown. We have shown here a
      colocalization between TDP-43 and the intracellular domain of APP (AICD) in the
      nucleus. Coimmunoprecipitation analysis showed an interaction between TDP-43 and
      AICD. Overexpression of TDP-43 in COS7 cells enhanced the transactivation of AICD
      in an APP-Gal4 luciferase reporter system. Real-time PCR analysis showed that
      cotransfection of TDP-43 and AICD in HEK293 cells increased P53 mRNA levels
      compared to either TDP-43-transfected or AICD-transfected cells. Moreover,
      cotransfection of TDP-43 and AICD in either N2a or COS7 cells showed increased
      numbers of apoptotic cells compared to either TDP-43-transfected or AICD
      transfected cells, indicating that TDP-43 enhances AICD-mediated apoptosis in N2a
      or COS7 cells. Thus, TDP-43 may play a role in AD pathology through interaction
      with AICD. 

PMID- 24721671
TI  - The cannabinoid CB2 receptor agonist GW405833 does not ameliorate brain damage
      induced by hypoxia-ischemia in rats.
AB  - The cannabinoid CB2 receptor has been under investigation as a potential target
      for neuroprotection with the suppression of neuroinflammation as the proposed
      mechanism of action. Several studies have now reported that CB2 agonists are
      neuroprotective in models of cerebral ischemia. However, these studies have
      tended to measure brain infarctions in rodents 1-3 days after drug administration
      and have not assessed behavioral outcomes. As it has been shown that apparent
      protection soon after injury is not necessarily correlated with improved outcome
      after several weeks, we tested the CB2 selective agonist GW405833 in a model of
      cerebral hypoxia-ischemia, and assessed histological and behavioral outcomes 15
      days after injury. Many putatively neuroprotective drugs have failed to translate
      from promising preclinical results to clinical success. We designed our
      experiments to not only stringently test CB2 mediated neuroprotection, but also
      to test several drug administration regimens to maximize the chance of detecting
      any therapeutic effect. However, GW405833 failed to provide neuroprotection in
      any of our experiments. These results challenge how far the results of earlier
      studies into CB2 mediated neuroprotection as measured at early time points may be
      extrapolated to later time points or to other models. 

PMID- 24721673
TI  - Proteomic profiling reveals that EhPC4 transcription factor induces cell
      migration through up-regulation of the 16-kDa actin-binding protein EhABP16 in
      Entamoeba histolytica.
AB  - Actin cytoskeleton is an essential structure involved in cell migration and
      invasion in parasites. In Entamoeba histolytica, the protozoan parasite causing
      human amoebiasis, the mechanisms underlying the expression of migration-related
      genes are poorly understood. Here, we investigated the biological effects of
      ectopic overexpression of EhPC4 (positive coactivator 4) in cell migration of E.
      histolytica trophozoites. Using differential in gel two-dimensional
      electrophoresis, 33 modulated proteins were detected in EhPC4-overexpressing
      cells. By electrospray ionization tandem mass spectrometry (ESI-MS/MS) analysis,
      16 of these proteins were identified. Interestingly, four up-regulated proteins
      involved in cytoskeleton organization and cell migration were identified.
      Particularly, we found the up-regulation of a 16-kDa actin-binding protein
      (EhABP16) which is a putative member of the cofilin/tropomyosin family involved
      in actin polymerization. EhPC4 overexpression induced a significant increase in
      migration of trophozoites and in the destruction of human SW480 colon cells.
      Consistently, silencing of gene expression by RNA interference of EhABP16
      significantly impairs cell migration. These changes were associated to
      alterations in the organization of actin cytoskeleton, and suppression of uropod
      like structure formation in EhABP16-deficient cells. In summary, we have
      uncovered novel proteins modulated by EhPC4, including EhABP16, with a potential
      role in cell migration, cytopathogenicity and virulence in E. histolytica.
      BIOLOGICAL SIGNIFICANCE: The human pathogen Entamoeba histolytica infects around
      50million people worldwide resulting in 40,000-100,000 deaths annually. Cell
      motility is a complex trait that is critical for parasites adaptation, spread and
      invasion processes into host tissues; it has been associated with virulence. In
      this study, we used a differential proteomic approach to demonstrate that E.
      histolytica EhPC4 induces changes in the expression of actin cytoskeleton
      proteins, including EhABP16, promoting a significant increase in cell motility
      and destruction of intestinal human cells. Particularly, we demonstrated for the
      first time that abrogation of EhABP16 impairs cell migration by altering the
      actin cytoskeleton dynamics and uropod-like structure formation in trophozoites.
      These data contribute to the understanding of molecular mechanisms that regulate
      virulence properties in this neglected protozoan parasite.

PMID- 24721674
TI  - Site-specific characterization of cell membrane N-glycosylation with integrated
      hydrophilic interaction chromatography solid phase extraction and LC-MS/MS.
AB  - Glycosylation of membrane proteins plays an important role in cellular behaviors
      such as cell-cell interaction, immunologic recognition and cell signaling.
      However, the effective extraction of membrane proteins, the selective isolation
      of glycopeptides and the mass spectrometric characterization of glycosylation are
      challenging with current analytical techniques. In this study, a systematic
      approach was developed which combined: an integrated hydrophilic interaction
      chromatography solid phase interaction (HILIC SPE) for simultaneous detergent
      removal and glycopeptide enrichment, and mass spectrometric identification of
      both protein N-glycosylation sites and site-specific glycan composition. The
      HILIC SPE conditions were optimized to enable the use of a high concentration of
      strong detergents, such as SDS and Triton X-100 and to dissolve highly
      hydrophobic membrane proteins, thus increasing the yield of membrane protein
      extraction. We illustrated the performance of this approach for the study of
      membrane protein glycosylation from human embryonic kidney cell lines (HEK 293T).
      200MUg total protein digest was processed using this approach, leading to the
      identification of 811 N-glycosylation sites from 567 proteins within two
      experimental replicates. Furthermore, 177 glycopeptides representing 82 N
      glycosites with both glycan composition and peptide sequence were identified by
      high energy collision dissociation. BIOLOGICAL SIGNIFICANCE: A method for
      systematic characterizing of cell membrane glycosylation has been developed in
      this manuscript. It is comprised of an integrated hydrophilic interaction
      chromatography solid phase extraction for the simultaneous detergent removal and
      intact glycopeptide enrichment. This HILIC SPE significantly increased the
      efficiency and sensitivity for glycosylation analysis and was combined with high
      energy collision dissociation to characterize site-specific N-glycosylation from
      HEK293 cell membrane. Totally 811 N-glycosylation sites from 567 proteins were
      identified and 177 intact glycopeptides with both glycan composition and peptides
      sequence were characterized, which provided a solution for site-specific N
      glycosylation characterization of membrane.

PMID- 24721676
TI  - Are pathological and oncological outcomes of elderly men treated with radical
      prostatectomy worse than those of younger men? Matched-pair analysis between
      patients aged <70 and >=70 years.
AB  - OBJECTIVE: To compare oncological outcomes of patients aged >=70 years treated
      with radical prostatectomy with those of a clinically matched younger cohort.
      METHODS: Data from 1268 patients undergoing radical prostatectomy between 2000
      and 2009 were retrospectively reviewed. Patients were classified according to age
      (<70 or >=70 years) at the time of prostatectomy. After matching pre-operative
      factors (i.e. prostate specific antigen, positive biopsy cores, Gleason score,
      clinical stage and D'Amico risk group), 333 patients were chosen from each group.
      RESULTS: The percentage of pathological stage >=T3 in those of age <70 and >=70
      years was 30.3 and 33.0%, respectively (P = 0.51). The percentage of pathological
      Gleason score <=6, 7 and >=8 was not significantly different between the two age
      groups (P = 0.08). The percentage of organ-confined disease in those of age <70
      and >=70 years was 69.4 and 67.0%, respectively (P = 0.56). With a median follow
      up of 50 months, 5-year prostate specific antigen recurrence-free survival in
      those of age <70 and >=70 years was 83.4 and 80.1%, respectively (log rank, P =
      0.199). Five-year cancer-specific survival in those of age <70 and >=70 years was
      100 and 99.4%, respectively (log rank, P = 0.317). Five-year overall survival in
      those of age <70 and >=70 years was 98.4 and 96.4%, respectively (log rank, P =
      0.228). CONCLUSIONS: Pathological and oncological outcomes in elderly patients
      (age >=70 years) treated with radical prostatectomy were not significantly
      different from those of younger patients (age <70 years). This information will
      help refine the indications for definitive treatment for localized prostate
      cancer in elderly men.

PMID- 24721677
TI  - [Prevalence of metabolic syndrome in children with and without obesity].
AB  - BACKGROUND AND OBJECTIVE: Childhood obesity is considered the main risk factor
      for the development of metabolic syndrome (MetS) during childhood, adolescence
      and adulthood. This study aimed to determine the prevalence of MetS components
      and its main defining combinations in a sample of school children with and
      without obesity. PATIENTS AND METHODS: A total of 225 children aged 6-12 years,
      106 obese and 119 with normal weight were included. MetS was defined by the
      presence of 3 or more of the following: obesity as a body mass index >= 95th
      percentile, fasting glucose >= 100 mg/dL, triglycerides >= 150 mg/dL, high
      density lipoproteins cholesterol (HDL-c)<40 mg/dL and systolic and diastolic
      blood pressure >= 95th percentile. RESULTS: We found MetS components in both
      groups. Most frequent abnormalities in the obese group included increased levels
      of HDL-c, triglycerides, fasting glucose and total cholesterol, while increased
      levels of glucose and total cholesterol, and lower HDL-c levels predominated in
      the normal weight group. The prevalence of MetS in the obese group was 44.3% and,
      in normal weight children, it was 0.84%. The 3 main components that defined the
      MetS in the obese group were obesity/triglycerides/HDL-c (34.0%),
      obesity/glucose/triglycerides/HDL-c (29.8%) and obesity/glucose/HDL-c (14.9%),
      while the only combination observed in the normal weight group was glucose/HDL
      c/triglycerides. CONCLUSION: A percentage of 44.3 of obese school children had
      MetS, and dyslipidemia showed to be strong determinants of MetS. Although the
      prevalence of MetS was low in children with normal weight, one third of them
      showed one of the components of MetS.

PMID- 24721675
TI  - A thermal window for yawning in humans: yawning as a brain cooling mechanism.
AB  - The thermoregulatory theory of yawning posits that yawns function to cool the
      brain in part due to counter-current heat exchange with the deep inhalation of
      ambient air. Consequently, yawning should be constrained to an optimal thermal
      zone or range of temperature, i.e., a thermal window, in which we should expect a
      lower frequency at extreme temperatures. Previous research shows that yawn
      frequency diminishes as ambient temperatures rise and approach body temperature,
      but a lower bound to the thermal window has not been demonstrated. To test this,
      a total of 120 pedestrians were sampled for susceptibly to self-reported yawn
      contagion during distinct temperature ranges and seasons (winter: 1.4 degrees C,
      n=60; summer: 19.4 degrees C, n=60). As predicted, the proportion of pedestrians
      reporting yawning was significantly lower during winter than in summer (18.3% vs.
      41.7%), with temperature being the only significant predictor of these
      differences across seasons. The underlying mechanism for yawning in humans, both
      spontaneous and contagious, appears to be involved in brain thermoregulation. 

PMID- 24721678
TI  - Multilocalized non-pigmenting fixed drug eruption caused by triclofos sodium.

PMID- 24721679
TI  - Genome sequencing, annotation and analysis of Salmonella enterica sub species
      salamae strain DMA-1.
AB  - BACKGROUND: The genus Salmonella is Gram-negative which belongs to the family
      Enterobacteriaceae. In this study, we have sequenced the whole genome of the
      strain DMA-1, which was isolated from mouse stool sample and identified as
      Salmonella enterica subspecies salamae. RESULTS: The strain DMA-1 was closely
      related at the 16S rRNA gene sequence level with the members of the genus
      Salmonella: Salmonella enterica subspecies salamae DSM 9220T (100%), followed by
      Salmonella enterica subspecies diarizonae (99.1%), Salmonella enterica subspecies
      enterica (99.0%) and Salmonella enterica subspecies indica (98.5%). We obtained
      the draft genome of S. enterica subspecies salamae strain DMA-1 with a size of
      4,826,209 bp and mean G+C content of 52.0 mol%. CONCLUSIONS: We for the first
      time, sequenced the entire genome of the strain DMA-1 which was isolated from the
      mouse stool sample and identified it as Salmonella enterica, sub species salamae.
      Further, we subjected the whole genome sequencing data for annotation that
      revealed several genes responsible for the pathogenesis, virulence, defense,
      metabolism and other genomic features.

PMID- 24721680
TI  - Clinical implications of distinct metastasizing preferences of different melanoma
      subtypes.
AB  - BACKGROUND: The incidence and mortality of malignant melanoma have been rising
      during the past decades, the latter being due to the high invasion capacity and
      the metastatic potential of melanoma cells to distant organs. OBJECTIVE: We
      investigated the distribution pattern of melanoma metastases taking into account
      different clinicopathological subtypes of melanoma. METHODS: We studied 310 stage
      IV (AJCC 2009) melanoma patients retrospectively with regard to potential
      correlations between frequency and occurrence of metastasis and the genetic
      background and pathological/clinical melanoma subtypes. For all patients, the
      time to distant metastasis (TTDM) and the distribution patterns of metastases
      were analyzed and correlated to the median survival time. RESULTS: Superficially
      Spreading (SSM) and Nodular melanomas (NMM) spread to the brain more frequently
      than Acrolentiginous (ALM) and Mucosal (MM) melanomas (p = 0.0012). The
      preference to affect the skeleton was significantly higher for ALM and MM in
      comparison to SSM and NMM (p = 0.0049). Lentigo maligna (LMM) tumors showed a
      significantly lower metastatic spread to distant lymph nodes (p = 0.0159). BRAF
      mutant versus wildtype tumors showed no significant differences concerning
      localization of metastasis but patients with BRAF mutant tumors were
      significantly younger at primary diagnosis and had a significantly shorter stage
      IV survival (p = 0.0106). CONCLUSION: This study shows a clear distinction of
      melanoma subtypes with regard to metastasizing preferences. Further knowledge
      about melanoma subtype specific characteristics, including molecular markers
      predictive of homing preferences, may help to understand and manage this
      heterogeneous disease in terms of prognosis and follow-up procedures.

PMID- 24721681
TI  - Ultrafast CEST imaging.
AB  - We describe a new MR imaging method for the rapid characterization or screening
      of chemical exchange saturation transfer (CEST) contrast agents. It is based on
      encoding the chemical shift dimension with an additional gradient as proposed in
      previous ultrafast CEST spectroscopy approaches, but extends these with imaging
      capabilities. This allows us to investigate multiple compounds simultaneously
      with an arbitrary sample tube arrangement. The technique requires a fast
      multislice readout to ensure the saturation is not lost during data acquisition
      due to T1 relaxation. We therefore employ radial subsampling, acquiring only 10
      projections per CEST image with a 128*128 matrix. To recover the images, we use a
      heuristic reconstruction algorithm that incorporates low rank and limited object
      support as prior knowledge. This way, we are able to acquire a spectral CEST data
      set consisting of 15 saturation offsets more than 16 times faster than compared
      with conventional CEST imaging. 

PMID- 24721682
TI  - The effect of insulin on circulating PCSK9 in postmenopausal obese women.
AB  - BACKGROUND: PCSK9 (proprotein convertase subtilisin/kexin type 9) promotes the
      degradation of the LDLR (LDL receptor) in hepatocytes, leading to an increase in
      plasma LDL-C (LDL cholesterol). Previous animal studies have shown that insulin
      stimulates PCSK9 transcription and observational human studies showed a positive
      correlation between plasma PCSK9 concentration and fasting insulinemia.
      OBJECTIVE: The purpose of this study was to investigate the effects of chronic
      and acute hyperinsulinemia on PCSK9 in a large cohort of human subjects as well
      as at a cellular level. METHODS: The in vivo effect of hyperinsulinemia on plasma
      PCSK9 concentration was studied using euglycemic-hyperinsulinemic clamps in 82
      non-diabetic post-menopausal obese patients. We studied the in vitro effects of
      insulin stimulation on PCSK9 mRNA as well as on protein expression and secretion
      in HepG2 and Huh7 cells. RESULTS: Analysis of the pre and post-clamp data
      revealed a 15.4% (p<0.001) lowering of plasma PCSK9 concentration after acute
      insulin induction. In vitro studies post-insulin stimulation showed that mRNA
      levels of PCSK9 reduced by 25% in HepG2 cells (p<0.027) and by 59% in Huh7 cells
      (p<0.01). Intracellular concentration of PCSK9 were 10% lower in HepG2 cells
      (p<0.05) and 35% lower in Huh7 cells (p<0.05). CONCLUSIONS: Our results show an
      inhibitory effect of acute hyperinsulinemia on PCSK9 in humans both in vitro and
      in vivo. This data may assist in evaluating PCSK9 levels in individuals on
      insulin therapy.

PMID- 24721683
TI  - Plasma neutrophil gelatinase-associated lipocalin levels are markedly increased
      in patients with non-transfusion-dependent thalassemia: Lack of association with
      markers of erythropoiesis, iron metabolism and renal function.
AB  - BACKGROUND: Neutrophil Gelatinase-Associated Lipocalin (NGAL) (known as NGAL,
      Lipocalin 2, Siderocalin, Uterocalin, proteinase-3 and 24p3) is a mammalian small
      25-kD peptide that belongs to the lipocalin superfamily, which consists of about
      20 small lipoproteins. NGAL was initially discovered as an antibacterial factor
      of natural immunity and an acute-phase protein. NGAL is also an iron trafficking
      protein, a member of the non-transferrin-bound iron (NTBI) pool and an
      alternative to the transferrin-mediated iron-delivery pathway. Of note, NTBI,
      which is elevated in thalassemic patients, induces cellular toxicity. In this
      study we investigated the possible association of NGAL with parameters of
      erythropoiesis, iron metabolism and renal injury in patients with non-transfusion
      dependent thalassemia (thalassemia intermedia or TI). PATIENTS AND METHODS:
      Thirty-five patients with TI, 13 men and 22 women, aged 8-63 years, were included
      in the study, while, 20 healthy individuals served as controls. Plasma NGAL
      levels were determined using an immunoenzymatic technique. Erythroid marrow
      activity was estimated by measuring soluble transferrin receptors (sTfR) levels
      with a turbidimetric technique. NTBI levels were determined using electrothermal
      atomic absorption spectrometry. Cystatin C, beta2-microglobulin and hs-CRP
      concentrations were measured by means of immunonephelometric techniques. RESULTS:
      The main results of the study showed: a) NGAL levels were significantly higher in
      patients with TI compared to controls (139.1 +/- 86.1 vs 51.2 +/- 11.8 MUg/L,
      p<0.0001), without significant effect of splenectomy or hydroxyurea on NGAL
      levels. Only 4 patients had NGAL levels within the control group range, b) no
      correlation was found between NGAL levels and either the parameters of
      erythropoiesis Hb, Hb F, reticulocytes and sTfR (p>0.66, p>0.67, p>0.63 and
      p>0.81 respectively), or with those of iron metabolism ferritin and NTBI (p>0.90
      and p>0.95 respectively). CONCLUSIONS: The increased NGAL levels reported for the
      first time in TI patients in this study are in agreement with the elevated
      expression of NGAL observed in TI mouse models. We postulate that the induction
      of NGAL in these patients may represent either a survival response, facilitating
      the survival of the less damaged thalassemic erythroid precursors, or a
      consequence of the abnormal iron regulation in TI.

PMID- 24721684
TI  - Multi-center analytical evaluation of a novel automated tacrolimus immunoassay.
AB  - BACKGROUND: Tacrolimus (TAC) is a post-transplantation immunosuppressant drug
      used in patients for whom careful monitoring of TAC concentration is essential. A
      new semi-automated immunoassay for TAC measurement, the Elecsys Tacrolimus assay,
      is available and has been assessed in a multi-center evaluation. METHODS:
      Residual whole blood samples from patients undergoing TAC therapy after organ
      transplant were used in assay evaluation at five clinical laboratories in Europe.
      Experiments included imprecision according to CLSI EP5-A2 (within-run and
      intermediate), functional sensitivity, linearity according to CLSI EP6-A, and
      recovery from external quality assessment scheme (EQAS) samples. The assay was
      compared to LC-MS/MS used routinely at each investigational site, and to the
      Abbott Architect immunoassay. RESULTS: Linearity from 0.5 to 40 MUg/L was
      observed and functional sensitivity of 0.3 MUg/L (CV <= 20%) was determined.
      Within-run imprecision was <= 5.1% on cobas e 602 (5.1% at 1.5 MUg/L) and <= 8.9%
      (8.9% at 0.8MUg/L) on cobas e 411. The intermediate imprecision for TAC
      concentrations >= 6.8 MUg/L was <= 6.5%. At lower therapeutic concentrations (to
      1.5 MUg/L) it was consistently <= 10%. Deming regression analysis of method
      comparison to LC-MS/MS yielded slopes of 1.07 (95%CI: 1.05/1.10) for heart
      transplant samples, 1.13 (95%CI: 1.09/1.16) for kidney, and 1.05 (95%CI:
      1.02/1.08) for lung transplant samples. CONCLUSIONS: The Elecsys Tacrolimus assay
      has good linearity, functional sensitivity and intermediate imprecision and is
      comparable to LC-MS/MS methods. The over-all performance of ECLIA demonstrates a
      modern generation TAC assay that meets the demands of monitoring drug
      concentrations in current immunosuppressive regimens.

PMID- 24721685
TI  - Exercise intolerance and the impact of physical activity in children treated with
      hematopoietic stem cell transplantation.
AB  - Hematopoietic stem-cell transplant (SCT) is increasingly used to treat children
      with cancer, and survival following SCT is improving. One predominant consequence
      of childhood cancer therapy is increased physical morbidity, which is worse in
      pediatric SCT recipients compared with children treated with chemotherapy or
      radiation alone. There are many factors that contribute to exercise intolerance
      and reduced physical function during the pretransplant, peritransplant, and
      posttransplant phases. These include side effects from chemotherapy or radiation,
      excessive immobility due to bed rest, infections, the negative effects of
      immunosuppressants, and graft vs host disease, all of which can impair
      cardiorespiratory fitness, muscle strength, and muscle function. Few studies have
      investigated the effects of exercise in childhood SCT recipients. In a small
      number of published studies, exercise interventions have been demonstrated to
      improve cardiorespiratory fitness, preserve or increase muscle mass, and improve
      muscle strength in children following SCT. The use of exercise as medicine may be
      a noninvasive and nonpharmaceutical treatment to target physical complications
      post-SCT. Researchers and health-care professionals should work together to
      develop exercise prescription guidelines for this unique and important
      population. 

PMID- 24721686
TI  - An improved peptide-spectral matching algorithm through distributed search over
      multiple cores and multiple CPUs.
AB  - BACKGROUND: A real-time peptide-spectrum matching (RT-PSM) algorithm is a
      database search method to interpret tandem mass spectra (MS/MS) with strict time
      constraints. Restricted by the hardware and architecture of individual
      workstation, previous RT-PSM algorithms either are not fast enough to satisfy all
      real-time system requirements or need to sacrifice the level of inference
      accuracy to provide the required processing speed. RESULTS: WE DEVELOP TWO
      PARALLELIZED ALGORITHMS FOR MS/MS DATA ANALYSIS: a multi-core RT-PSM (MC RT-PSM)
      algorithm which works on individual workstations and a distributed computing RT
      PSM (DC RT-PSM) algorithm which works on a computer cluster. Two data sets are
      employed to evaulate the performance of our proposed algorithms. The simulation
      results show that our proposed algorithms can reach approximately 216.9-fold
      speedup on a sub-task process (similarity scoring module) and 84.78-fold speedup
      on the overall process compared with a single-thread process of the RT-PSM
      algorithm when 240 logical cores are employed. CONCLUSIONS: The improved RT-PSM
      algorithms can achieve the processing speed requirement without sacrificing the
      level of inference accuracy. With some configuration adjustments, the proposed
      algorithm can support many peptide identification programs, such as X!Tandem,
      CUDA version RT-PSM, etc.

PMID- 24721687
TI  - Systematic approach to assess biohydrogen potential of anaerobic sludge and soil
      rhizobia as biocatalysts: Influence of crucial factors affecting acidogenic
      fermentation.
AB  - A systematic protocol was designed to enumerate the variation in biohydrogen
      production with two different biocatalysts (sludge and soil) under different pH
      and organic loads. Both the biocatalysts showed cumulatively higher H2 production
      under acidogenic condition (pH 6) than at neutral pH condition. The cumulative
      hydrogen production was non-linearly fitted with modified Gompertz model and
      statistically validated. Pretreated soil biocatalyst showed relatively higher H2
      production (OLR II, 142+/-5ml) than pretreated sludge (OLR I, 123+/-5ml); which
      was evidenced by substrate linked dehydrogenase activity and bio-electrochemical
      analysis. Experimental results revealed agricultural soil as a better biocatalyst
      than anaerobic sludge for all the operated process conditions. The voltammogram
      profiles and Tafel slopes revealed dominance of reductive catalytic activity of
      the pretreated inoculums substantiating dark-fermentation. Soil consortia showed
      low polarization resistance (2.24kOmega) and high reductive electron transfer
      efficiency (1.17 Vdec(-1)) at a high organic load; thus, rebating high H2
      production. 

PMID- 24721688
TI  - Response to letter to the editor.

PMID- 24721689
TI  - Lack of interleukin-17 leads to a modulated micro-environment and amelioration of
      mechanical hypersensitivity after peripheral nerve injury in mice.
AB  - Interleukin-17 (IL-17) is involved in a wide range of inflammatory disorders and
      in recruitment of inflammatory cells to injury sites. A recent study of IL-17
      knock-out mice revealed that IL-17 contributes to neuroinflammation and
      neuropathic pain after peripheral nerve injury. Surprisingly, little is known of
      micro-environment modulation by IL-17 in injured sites and in pathologically
      related neuroinflammation and chronic neuropathic pain. Therefore, we
      investigated nociceptive sensitization, immune cell infiltration, myeloperoxidase
      (MPO) activity, and expression of multiple cytokines and opioid peptides in
      damaged nerves of wild-type (IL-17(+/+)) and IL-17 knock-out (IL-17(-/-)) mice
      after partial sciatic nerve ligation. Our results demonstrated that the IL-17(-/
      ) mice had less behavioral hypersensitivity after partial sciatic nerve ligation,
      and inflammatory cell infiltration and pro-inflammatory cytokine (tumor necrosis
      factor-alpha, IL-6, and interferon-gamma) levels in damaged nerves were
      significantly decreased, with the levels of anti-inflammatory cytokines IL-10 and
      IL-13, and expressions of enkephalin, beta-endorphin, and dynorphin were also
      decreased compared to those in wild-type control mice. In conclusion, we provided
      evidence that IL-17 modulates the micro-environment at the level of the
      peripheral injured nerve site and regulates progression of behavioral
      hypersensitivity in a murine chronic neuropathic pain model. The attenuated
      behavioral hypersensitivity in IL-17(-/-) mice could be a result of decreased
      inflammatory cell infiltration to the injured site, resulting in modulation of
      the pro- and anti-inflammatory cytokine milieu within the injured nerve.
      Therefore, IL-17 may be a critical component for neuropathic pain pathogenesis
      and a novel target for therapeutic intervention for this and other chronic pain
      states.

PMID- 24721690
TI  - Altered experimental pain perception after cerebellar infarction.
AB  - Animal studies have suggested that the cerebellum, in addition to its motor
      functions, also has a role in pain processing and modulation, possibly because of
      its extensive connections with the prefrontal cortex and with brainstem regions
      involved in descending pain control. Consistently, human imaging studies have
      shown cerebellar activation in response to painful stimulation. However, it is
      presently not clear whether cerebellar lesions affect pain perception in humans.
      In the present study, we used experimental pain testing to compare acute pain
      perception and endogenous pain inhibition in 30 patients 1 to 11 years after
      cerebellar infarction and in 30 sex- and age-matched healthy control subjects.
      Compared to controls, patients exhibited a significantly increased pain
      perception in response to acute heat stimuli (44  degrees C-48  degrees C,
      average pain intensity rating for patients 3.4+/-2.8 and for controls 1.5+/-1.7
      [on a numeric rating scale of 0-10], P<.01) and to repeated 256 mN pinprick
      stimuli (1.3+/-1.9 vs. 0.6+/-1.0 [0-10], P<.05). Heat hyperalgesia in patients
      was more pronounced on the body side ipsilateral to the infarction. In addition,
      patients showed reduced offset analgesia (change in pain intensity rating: 0.0%+/
      15.8% vs. -16.9%+/-36.3%, P<.05) and reduced placebo analgesia (change in pain
      intensity rating: -1.0+/-1.1 vs. -1.8+/-1.3 [0-10], P<.05) compared to controls.
      In contrast, heat and pressure pain thresholds were not significantly different
      between groups. These results show that, after cerebellar infarction, patients
      perceive heat and repeated mechanical stimuli as more painful than do healthy
      control subjects and have deficient activation of endogenous pain inhibitory
      mechanisms (offset and placebo analgesia). This suggests that the cerebellum has
      a previously underestimated role in human pain perception and modulation.

PMID- 24721691
TI  - Periodontal disease in patients with chronic coronary heart disease: Prevalence
      and association with cardiovascular risk factors.
AB  - AIM: There are reported links between periodontal disease (PD) and cardiovascular
      (CV) risk but data are lacking, especially from populations with established
      coronary heart disease (CHD). This study describes self-reported indicators of PD
      and associations with CV risk factors in a global stable CHD population. METHODS
      AND RESULTS: A total of 15,828 participants in the global STABILITY trial
      underwent a physical examination, blood sampling, and completed a lifestyle
      questionnaire. They reported remaining number of teeth (none, 1-14, 15-20, 21-25
      or 26-32 (all)) and frequency of gum bleeding (never/rarely, sometimes, often or
      always). Adjusted linear and logistic regression models assessed associations
      between tooth loss, gum bleeding, and socioeconomic and CV risk factors. A total
      of 40.9% of participants had <15 remaining teeth; 16.4% had no teeth; and 25.6%
      reported gum bleeding with large differences in prevalence among countries,
      regions and ethnic groups. Less tooth loss was associated with lower levels of
      glucose, low-density lipoprotein (LDL) cholesterol, systolic blood pressure,
      waist circumference and hs-CRP; higher estimated glomerular filtration rate;
      decreased odds for diabetes and smoking, and increased odds for higher education,
      alcohol consumption and work stress. Gum bleeding was associated with higher LDL
      cholesterol and systolic blood pressure; decreased odds for smoking, but
      increased odds for higher education, alcohol consumption and stress. CONCLUSION:
      Self-reported indicators of PD were common in this chronic CHD population and
      were associated with an increasing socioeconomic and CV risk factor burden.
      However, causality between self-reported PD and CV risk and outcome needs further
      investigation.

PMID- 24721692
TI  - Disentangling methodological and biological sources of gene tree discordance on
      Oryza (Poaceae) chromosome 3.
AB  - We describe new methods for characterizing gene tree discordance in phylogenomic
      data sets, which screen for deviations from neutral expectations, summarize
      variation in statistical support among gene trees, and allow comparison of the
      patterns of discordance induced by various analysis choices. Using an
      exceptionally complete set of genome sequences for the short arm of chromosome 3
      in Oryza (rice) species, we applied these methods to identify the causes and
      consequences of differing patterns of discordance in the sets of gene trees
      inferred using a panel of 20 distinct analysis pipelines. We found that
      discordance patterns were strongly affected by aspects of data selection,
      alignment, and alignment masking. Unusual patterns of discordance evident when
      using certain pipelines were reduced or eliminated by using alternative
      pipelines, suggesting that they were the product of methodological biases rather
      than evolutionary processes. In some cases, once such biases were eliminated,
      evolutionary processes such as introgression could be implicated. Additionally,
      patterns of gene tree discordance had significant downstream impacts on species
      tree inference. For example, inference from supermatrices was positively
      misleading when pipelines that led to biased gene trees were used. Several
      results may generalize to other data sets: we found that gene tree and species
      tree inference gave more reasonable results when intron sequence was included
      during sequence alignment and tree inference, the alignment software PRANK was
      used, and detectable "block-shift" alignment artifacts were removed. We discuss
      our findings in the context of well-established relationships in Oryza and
      continuing controversies regarding the domestication history of O. sativa.

PMID- 24721693
TI  - Two dimensional numerical prediction of deflagration-to-detonation transition in
      porous energetic materials.
AB  - This paper describes a two-dimensional code developed for analyzing two-phase
      deflagration-to-detonation transition (DDT) phenomenon in granular, energetic,
      solid, explosive ingredients. The two-dimensional model is constructed in full
      two-phase, and based on a highly coupled system of partial differential equations
      involving basic flow conservation equations and some constitutive relations
      borrowed from some one-dimensional studies that appeared in open literature. The
      whole system is solved using an optimized high-order accurate, explicit, central
      difference scheme with selective-filtering/shock capturing (SF-SC) technique, to
      augment central-diffencing and prevent excessive dispersion. The sources of the
      equations describing particle-gas interactions in terms of momentum and energy
      transfers make the equation system quite stiff, and hence its explicit
      integration difficult. To ease the difficulties, a time-split approach is used
      allowing higher time steps. In the paper, the physical model for the sources of
      the equation system is given for a typical explosive, and several numerical
      calculations are carried out to assess the developed code. Microscale
      intergranular and/or intragranular effects including pore collapse, sublimation,
      pyrolysis, etc. are not taken into account for ignition and growth, and a basic
      temperature switch is applied in calculations to control ignition in the
      explosive domain. Results for one-dimensional DDT phenomenon are in good
      agreement with experimental and computational results available in literature. A
      typical shaped-charge wave-shaper case study is also performed to test the two
      dimensional features of the code and it is observed that results are in good
      agreement with those of commercial software. 

PMID- 24721694
TI  - Sorption of organophosphate esters by carbon nanotubes.
AB  - Insights from the molecular-level mechanism of sorption of organophosphate esters
      (OPEs) on carbon nanotubes (CNTs) can further our understanding of the fate and
      transport of OPEs in the environment. The motivation for our study was to explore
      the sorption process of OPEs on multi-walled CNTs (MWCNTs), single-walled CNTs
      (SWCNTs) and their oxidized counterparts (O-MWCNTs and O-SWCNTs), and its
      molecular mechanism over a wide concentration range. The sorption isotherm
      results revealed that the hydrophobicity of OPEs dominated their affinities on a
      given CNT and the pi-pi electron donor-acceptor (EDA) interaction also played an
      important role in the sorption of aromatic OPEs. This pi-pi EDA interaction,
      verified with Raman and FT-IR spectroscopy, could restrict the radial vibration
      of SWCNTs and affect the deformation vibration gamma(CH) bands of OPE molecules.
      The OPE surface coverage on CNTs, estimated using the nonlinear Dubinin-Ashtakhov
      model, indicated that the oxygen-containing functional groups on CNTs could
      interact with water molecules by H-bonding, resulting in a decrease in effective
      sorption sites. In addition, FTIR analysis also confirmed the occurrence of
      Bronsted acid-base interactions between OPEs and surface OH groups of SWCNTs. Our
      results should provide mechanistic insights into the sorption mechanism of OPE
      contaminants on CNTs. 

PMID- 24721695
TI  - Adsorption of phthalic acid esters (PAEs) by amphiphilic polypropylene nonwoven
      from aqueous solution: the study of hydrophilic and hydrophobic microdomain.
AB  - A kind of amphiphilic polypropylene nonwoven with hydrophilic and hydrophobic
      microdomain was prepared through electron beam induced graft polymerization and
      subsequent ring opening reaction and then utilized in the adsorption of phthalic
      acid esters (PAEs). To elucidate the superiority of such amphiphilic microdomain,
      a unique structure without hydrophilic part was constructed as comparison. In
      addition, the adsorption behaviors including adsorption kinetics, isotherms and
      pH effect were systematically investigated. The result indicated that the
      amphiphilic structure and the synergy between hydrophilic and hydrophobic
      microdomain could considerably improve the adsorption capacities, rate and
      affinity. Particularly the existence of hydrophilic microdomain could reduce the
      diffusion resistance and energy barrier in the adsorption process. These
      adsorption results showed that the amphiphilic PP nonwoven have the potential to
      be used in environmental application. 

PMID- 24721697
TI  - Simultaneous determination of 18 tetrahydrocorticosteroid sulfates in human urine
      by liquid chromatography/electrospray ionization-tandem mass spectrometry.
AB  - A liquid chromatography (LC)/electrospray ionization (ESI)-mass spectrometry (MS)
      method for the direct determination of eighteen tetrahydrocorticosteroid sulfates
      in human urine has been developed. The analytes were 3- and 21-monosulfates and
      3,21-disulfates of tetrahydrocortisol (THF), tetrahydrocortisone (THE),
      tetrahydro-11-deoxycortisol (THS), and their corresponding 5alpha-H
      stereoisomers. The mass spectrometric behavior of these sulfates in negative-ion
      ESI-MS/MS revealed the production of intense structure specific product ions
      within the same group of sulfates and permitted distinction between regioisomeric
      sulfates by collision-induced fragmentation with the MS/MS technique using a
      linear ion-trap instrument. For the quantitative analysis, selected reaction
      monitoring analysis in the negative-ion detection mode using triple-stage
      quadrupole mass spectrometer was performed by monitoring transitions from [M-H](
      ) to the most abundant product ion of each tetrahydrocorticosteroid sulfate.
      After addition of 3- and 21-monosulfates of [2,2,3beta,4,4-d5]-THF, -THE, and 
      THS as internal standards, urine sample was applied to a solid phase extraction
      using a lipophilic-weak anion exchange cartridge column, and then analyzed by
      LC/ESI-MS/MS. The method had satisfactory performance in terms of intra- and
      inter-assay precision (less than 9.7% and 9.6%, respectively), and accuracy (91.2
      108.2%). The limit of quantification was lower than 2.5 ng/mL for all sulfates
      examined. We applied this method to determine the concentration of eighteen
      tetrahydrocorticosteroid sulfates in the urine of healthy subjects. Thus, we have
      developed a sensitive, precise and accurate assay for urinary
      tetrahydrocorticosteroid sulfates that should be useful for clinical and
      biological studies.

PMID- 24721696
TI  - Gold nanoparticles hosted in a water-soluble silsesquioxane polymer applied as a
      catalytic material onto an electrochemical sensor for detection of nitrophenol
      isomers.
AB  - The water-soluble 3-n-propyl-4-picolinium silsesquioxane chloride (Si4Pic(+)Cl(
      )) polymer was prepared, characterized and used as a stabilizing agent for the
      synthesis of gold nanoparticles (nAu). The ability of Si4Pic(+)Cl(-) to adsorb
      anionic metal complexes such as AuCl4(-) ions allowed well-dispersed nAu to be
      obtained with an average particle size of 4.5nm. The liquid suspension of nAu
      Si4Pic(+)Cl(-) was deposited by the drop coating method onto a glassy carbon
      electrode (GCE) surface to build a sensor (nAu-Si4Pic(+)Cl(-)/GCE) which was used
      for the detection of o-nitrophenol (o-NP) and p-nitrophenol (p-NP). Under
      optimized experimental conditions the reduction peak current increased with
      increasing concentrations of both nitrophenol isomers in the range of 0.1
      1.5MUmolL(-1). The detection limits were 46nmolL(-1) and 55nmolL(-1) for o-NP and
      p-NP, respectively. These findings indicate that the nAu-Si4Pic(+)Cl(-) material
      is a very promising candidate to assemble electrochemical sensors for practical
      applications in the field of analytical chemistry. 

PMID- 24721698
TI  - Intervention thresholds: a conceptual frame for advance care planning choices.
AB  - BACKGROUND: Advance care planning (ACP) provides for decisions in the event of
      decisional incapacity. Determining ahead of time what a person may want is
      challenging and limits the utility of ACP. We present empirical evidence for a
      new approach to ACP: the individual's "intervention threshold." The intervention
      threshold is intuitively understood by clinicians and lay people, but has not
      been thoroughly described, measured, or analyzed. METHODS: Using a mixed-methods
      approach to address the concept of the intervention thresholds, we recruited 52
      subjects from a population of chronically ill outpatients for structured
      telephone interviews assessing knowledge, attitudes, and prior ACP activities.
      Respondents were presented with 11 interventions for each of four medical
      scenarios. For each scenario, they were asked whether they would accept each
      intervention. Data was evaluated by descriptive statistics and chi-squared
      statistics. RESULTS: Complete data were obtained from 52 patients, mean age of
      64.5, 34.6% of whom were male. Only 17.3% reported prior ACP discussion with a
      physician. Rates of accepting and refusing interventions varied by scenario (p <
      0.0001) and intervention intensity (p < 0.0001). CONCLUSIONS: These data provide
      evidence that people display transitions between wanting or not wanting
      interventions based on scenarios. Further research is needed to determine
      effective ways to identify, measure, and represent the components of an
      individual's intervention threshold in order to facilitate informed decision
      making during future incapacity.

PMID- 24721699
TI  - Recommendations for adjunctive basic skin care in patients with psoriasis.
AB  - BACKGROUND: Psoriasis is a multifactorial disease involving both genetic
      predisposition and external triggers, resulting in epidermal and immune
      dysfunctions. Regardless of the severity of the disease, patients require
      additional basic topical treatment with emollients. Basic skin care products are
      well known for their role in moisture retention and symptom control in psoriasis,
      yet patients underuse them. Dry skin and cutaneous inflammation are associated
      with an impaired epidermal barrier function. This breakdown of the skin barrier
      causes the release of pro-inflammatory mediators that exaggerate inflammation.
      OBJECTIVES: to provide recommendations for the use of emollients (including
      ceramides, urea, keratolytic agents, zinc salts, niacinamide), thermal water and
      skin care products in psoriasis. METHODS: A review of the current literature from
      2000 to 2012 using Medline and Ovid was performed by a working group of five
      European Dermatologists with clinical and research experience in psoriasis.
      RESULTS: Either alone or used adjunctively, basic topical therapy can restore and
      protect skin barrier function, increase remission times between flare-ups and
      enhance the effects of pharmaceutical therapy. CONCLUSION: We provide physicians
      with a tool to assist them in implementing basic skin care in an integrated
      disease management approach.

PMID- 24721700
TI  - T and B cells participate in bone repair by infiltrating the fracture callus in a
      two-wave fashion.
AB  - Fracture healing is a regenerative process in which bone is restored without scar
      tissue formation. The healing cascade initiates with a cycle of inflammation,
      cell migration, proliferation and differentiation. Immune cells invade the
      fracture site immediately upon bone damage and contribute to the initial phase of
      the healing process by recruiting accessory cells to the injury site. However,
      little is known about the role of the immune system in the later stages of
      fracture repair, in particular, whether lymphocytes participate in soft and hard
      callus formation. In order to answer this question, we analyzed femoral fracture
      healing in mice by confocal microscopy. Surprisingly, after the initial
      inflammatory phase, when soft callus developed, T and B cells withdrew from the
      fracture site and were detectable predominantly at the femoral neck and knee.
      Thereafter lymphocytes massively infiltrated the callus region (around day 14
      after injury), during callus mineralization. Interestingly, lymphocytes were not
      found within cartilaginous areas of the callus but only nearby the newly forming
      bone. During healing B cell numbers seemed to exceed those of T cells and B cells
      progressively underwent effector maturation. Both, osteoblasts and osteoclasts
      were found to have direct cell-cell contact with lymphocytes, strongly suggesting
      a regulatory role of the immune cells specifically in the later stages of
      fracture healing. 

PMID- 24721701
TI  - Myokines (muscle-derived cytokines and chemokines) including ciliary neurotrophic
      factor (CNTF) inhibit osteoblast differentiation.
AB  - Muscle and bone are intimately linked by bi-directional signals regulating both
      muscle and bone cell gene expression and proliferation. It is generally accepted
      that muscle cells secrete factors (myokines) that influence adjacent bone cells,
      but these myokines are yet to be identified. We have previously shown that
      osteocyte-specific deletion of the co-receptor subunit utilized by IL-6 family
      cytokines, glycoprotein 130 (gp130), resulted in impaired bone formation in the
      trabecular bone, but enhanced periosteal expansion, suggesting a gp130-dependent
      periosteum-specific inhibition of osteoblast function, potentially induced by the
      local muscle fibres. We report here that differentiated primary calvarial
      osteoblasts cultured in myotube-conditioned media (CM) from myogenic C2C12 cells
      show reduced mRNA levels of genes associated with osteoblast differentiation.
      Alkaline phosphatase protein activity and all mRNA markers of osteoblast
      differentiation in the tested panel (runx2, osterix, alkaline phosphatase,
      parathyroid hormone (PTH) receptor, osteoprotegerin, osteocalcin, sclerostin)
      were reduced following culture with myotube CM. The exception was RANKL, which
      was significantly elevated in differentiated primary osteoblast cultures
      expressing osteocytic genes. A cytokine array of the C2C12 myotube-conditioned
      media identified TIMP-1 and MCP-1 as the most abundant myokines, but treatment
      with recombinant TIMP-1 or MCP-1 did not inhibit osteoblast gene expression.
      Rather, the IL-6 family cytokine ciliary neurotrophic factor (CNTF), which we
      found abundantly expressed by mouse muscle at the transcript and protein level,
      reduced osteoblast gene expression, although not to the same extent as the
      myotube-conditioned media. These data indicate that muscle cells secrete abundant
      TIMP-1, MCP-1, and CNTF, and that of these, only CNTF has the ability to suppress
      osteoblast function and gene expression in a similar manner to myotube
      conditioned medium. This suggests that CNTF is an inhibitory myokine for
      osteoblasts. 

PMID- 24721703
TI  - Sublethal radionecrosis after prolonged radioscopy: multiple systems issues in
      interventional cardiology.

PMID- 24721702
TI  - Host defence related responses in bovine milk during an experimentally induced
      Streptococcus uberis infection.
AB  - BACKGROUND: Milk contains a range of proteins of moderate or low abundance that
      contribute to host defence. Characterisation of these proteins, the extent to
      which their abundance is regulated by pathogenic stimuli, and the variability of
      their response between and within individual animals would facilitate a better
      understanding of the molecular basis for this important function of milk.
      RESULTS: We have characterised the host defence proteins in bovine milk and their
      responses to intra-mammary infection by a common Gram positive mastitis pathogen,
      Streptococcus uberis, using a combination of 2D gel electrophoresis and GeLC mass
      spectrometry. In total, 68 host defence-associated proteins were identified, 18
      of which have a direct antimicrobial function, 23 of which have a pathogen
      recognition function, and 27 of which have a role in modulating inflammatory or
      immune signalling. The responsiveness of seven proteins was quantified by western
      blotting; validating the proteomic analyses, quantifying the within- and between
      animal variability of the responses, and demonstrating the complexity and
      specificity of the responses to this pathogen. CONCLUSIONS: These data provide a
      foundation for understanding the role of milk in host-microbe interaction.
      Furthermore they provide candidate biomarkers for mastitis diagnosis, and will
      inform efforts to develop dairy products with improved health-promoting
      properties.

PMID- 24721705
TI  - Evolution of peripheral blood T lymphocyte subsets after allogenic or autologous
      hematopoietic stem cell transplantation.
AB  - With the aim to search for differences in T cell reconstitution after allogenic
      or autologous hematopoietic stem cell transplantation (HSCT), we characterized
      peripheral blood T-cell subsets by means of flow cytometry, in adult patients who
      had undergone either allogenic (n=23) or autologous (n=29) HSCT for the treatment
      of hematological malignancies. The patients were followed every 3 months for 21
      months after HSCT. Compared to healthy controls (n=20 blood donors), the two
      transplanted groups displayed (i) a CD4 lymphopenia, (ii) a low percentage of
      naive T cells, (iii) high percentages of memory T cells and of activated T cells
      (HLA-DR+, CD25+) and high percentages of CD4 T cells with a high expression of
      CD25. The levels of TRECs (TCR rearrangement excision circles) were not
      significantly different between the two groups. In total, the differences of the
      nature and the speed of T lymphocyte reconstitution observed between the two
      patient groups were minor. This leads us to conclude that in allografted
      patients, lymphocyte activation as well as many other disturbances of
      subpopulations of peripheral blood lymphocytes are probably not related to the
      allogenicity of the graft, but are due to the expansion of T cells transfused
      with HSC and slow differentiation of T lymphocytes in the thymus progressively
      colonized by bone marrow-derived T-cell precursors. 

PMID- 24721706
TI  - hIL-15 gene-modified human natural killer cells (NKL-IL15) augments the anti
      human hepatocellular carcinoma effect in vivo.
AB  - Genetic modification of NK cells may provide new possibilities for developing
      effective cancer immunotherapy by improving NK cell function and specificity. We
      previously established human interleukin-15 (hIL-15) gene-modified NKL cells (NKL
      IL15) and demonstrated their therapeutic efficiency against human hepatocellular
      carcinoma (HCC) in vitro. To further assess the applicability of NKL-IL15 cells
      in adoptive cellular immunotherapy, we further investigated their natural
      cytotoxicity against HCC in vivo in the present study. NKL-IL15 cells exhibited
      strong inhibition on the growth of transplanted human HCC tumors in xenograft
      nude mouse models. Further investigation showed that NKL-IL15 cells expressed
      much higher levels of cytolysis-related molecules, including NKp80, TRAIL,
      granzyme B, IFN-gamma, and TNF-alpha, than parental NKL cells in response to HCC
      stimulation. Moreover, soluble mediators secreted by NKL-IL15 cells decreased HCC
      cell proliferation; in particular, NKL-IL15-derived TNF-alpha and IFN-gamma
      induced higher NKG2D ligand expression on target cells and resulted in the
      increased susceptibility of HCCs to NKL-mediated cytolysis. These results show
      that hIL-15 gene-modified human NK cells can augment the anti-tumor effect of NK
      cells on human HCC in vivo and suggest their promising applicability as a new
      candidate for adoptive immunotherapy against HCCs in the future. 

PMID- 24721704
TI  - Analysis of the transcriptional networks underpinning the activation of murine
      macrophages by inflammatory mediators.
AB  - Macrophages respond to the TLR4 agonist LPS with a sequential transcriptional
      cascade controlled by a complex regulatory network of signaling pathways and
      transcription factors. At least two distinct pathways are currently known to be
      engaged by TLR4 and are distinguished by their dependence on the adaptor molecule
      MyD88. We have used gene expression microarrays to define the effects of each of
      three variables--LPS dose, LPS versus IFN-beta and -gamma, and genetic background
      -on the transcriptional response of mouse BMDMs. Analysis of correlation networks
      generated from the data has identified subnetworks or modules within the
      macrophage transcriptional network that are activated selectively by these
      variables. We have identified mouse strain-specific signatures, including a
      module enriched for SLE susceptibility candidates. In the modules of genes unique
      to different treatments, we found a module of genes induced by type-I IFN but not
      by LPS treatment, suggesting another layer of complexity in the LPS-TLR4
      signaling feedback control. We also observe that the activation of the complement
      system, in common with the known activation of MHC class 2 genes, is reliant on
      IFN-gamma signaling. Taken together, these data further highlight the exquisite
      nature of the regulatory systems that control macrophage activation, their likely
      relevance to disease resistance/susceptibility, and the appropriate response of
      these cells to proinflammatory stimuli.

PMID- 24721707
TI  - The reduced proportion of New splenic T-cells in the zinc-deficient growing rat
      is not due to increased susceptibility to apoptosis.
AB  - Dietary zinc deficiency has been associated with an increased risk of infection.
      It has been reported that zinc-deficient rats have fewer New T-cells
      (TCRalphabeta(+)CD90(+)) compared to diet-restricted and control rats, which over
      time could adversely affect the ability of the organism to fight off infections.
      We hypothesized that the lower proportion of New T-cells in zinc deficiency is
      due to an increased susceptibility to apoptosis. Weanling, Sprague Dawley rats
      were assigned to one of four dietary treatment groups for 3 weeks: zinc-deficient
      (ZD, <1mg zinc/kg, ad libitum), diet-restricted (DR, 30mg zinc/kg, limited to the
      amount of feed as consumed by ZD), marginally zinc-deficient (MZD, 10mg zinc/kg,
      ad libitum) or control (CTL, 30mg zinc/kg, ad libitum). Thymocytes and
      splenocytes were labeled for flow cytometric determination of cell surface
      markers and DNA staining (for simultaneous determination of the phenotype of
      apoptotic cells) and assessed by Western blotting for apoptotic markers. Cells
      were analyzed immediately, or after incubation for 7h with or without
      dexamethasone. There was no difference in the proportion of CD90(+) thymocytes;
      however ZD rats had a higher proportion of Cytotoxic (CD90(+)4(-)8(+)) thymocytes
      compared to MZD and CTL. ZD had a lower proportion of splenic New T-cells
      compared to DR, MZD and CTL. There was no effect of diet on the proportion of
      apoptotic thymocytes or splenocytes, except ZD splenoctyes had a lower Bax/Bcl-xl
      ratio compared to DR and CTL. We characterized the splenic New T-cells into
      Helper and Cytotoxic subsets and found that ZD had a higher ratio of Helper to
      Cytotoxic New T-cells compared to MZD and CTL. These results do not support the
      hypothesis of increased apoptotic removal of New T-cells in ZD in growing rats.
      The regulation of CD90 expression should be explored in future studies. 

PMID- 24721709
TI  - Superconducting properties of hole doped Ba(0.6)Li(0.4)Fe2As2 single crystal.
AB  - We report the emergence of superconductivity in Li doped Ba-122 single crystals
      grown by the Bridgman method. The superconducting transition temperature Tc,onset
      is around 19 K. The specific heat capacity C/T shows a weak anomaly near Tc. The
      value of DeltaC/gammanTc is smaller than the value predicted in BCS theory
      indicating a multigap nature of the sample. The magnetic measurements show that
      the lower critical field Hc1(T) exhibits a linear temperature dependence, with a
      pronounced change of the Hc1(T) curvature around 0.4Tc and Hc1(0) ~ 430 Oe in the
      Ba0.6Li0.4Fe2As2 single crystal. Furthermore, temperature dependence of the
      penetration depth lambda(T) follows a power law (~T(n)) below 0.4Tc which
      predicts possible S+/--wave pairing in a Ba0.6Li0.4Fe2As2 superconductor. Over a
      wide range of temperatures, the Jc(H) exhibits a relation J(c)[proportionality]
      H(-alpha) with alpha = 0.5 ~ 0.6 for H || c and H || ab which indicates random
      defects in the sample. We found that the temperature dependence of the critical
      current density Jc(T) can be fitted well with the deltal-type pinning model,
      whose origin is attributed to spatial variations of charge carrier mean free path
      l. We suggest that the large mismatch in the ionic radius of Ba and Li can affect
      the irreversible magnetic properties of the Ba0.6Li0.4Fe2As2 single crystal
      without any structural transition.

PMID- 24721711
TI  - The occurrence of thermotolerant Campylobacter spp. in raw meat intended for
      public catering.

PMID- 24721710
TI  - Placental mesenchymal stem cells of fetal and maternal origins demonstrate
      different therapeutic potentials.
AB  - INTRODUCTION: Therapeutic potentials of mesenchymal stem cells (MSCs) from
      different sources have been evaluated in pre-clinical and clinical settings.
      Although MSCs from different sources share MSC-specific characteristics and
      functions, inconsistent or controversial results of pre-clinical and clinical
      applications of such cells are frequently reported. This may be partially due to
      the fact that MSCs isolated from different origins may differentially express
      some functions not typical for MSCs, and hence have different therapeutic
      potentials. The aim of this study is to investigate the differences in human
      placental MSCs (P-MSCs) of fetal and maternal origins in the aspects of clinical
      importance. METHODS: P-MSCs of fetal and maternal origins isolated from normal
      term placentas were characterized for their typical phenotype as well as their
      expression of receptors and growth factors of clinic interests. P-MSCs that
      preferentially express hepatocyte growth factor (HGF) and CD200 were evaluated
      for their therapeutic potentials in models of angiogenesis and allogeneic skin
      transplantation, in comparison with their HGF and CD200 negative partners.
      RESULTS: Although all P-MSCs express typical MSC phenotype, fetal but not
      maternal P-MSCs express high levels of CD200 and HGF. Compared with HGF and CD200
      negative P-MSCs, HGF and CD200 positive cells demonstrated significantly high
      potentials in promoting angiogenesis in vitro and increasing immunosuppressive
      function in vivo. These therapeutic potentials were at least in part due to their
      differences in HGF and CD200 expression, respectively. CONCLUSIONS: We conclude
      that MSC origins may have significant impact on the therapeutic potentials of
      such cells, and should be taken into consideration in clinical applications.

PMID- 24721712
TI  - 'The clock keeps ticking'--the role of a community-based intervention in reducing
      delays in seeking emergency obstetric care in rural Bangladesh: a quasi
      experimental study.
AB  - OBJECTIVE: To explore the role of a community-based intervention in reducing
      delays in accessing emergency obstetric care (EmOC) in rural Bangladesh, and the
      factors associated with delayed decision making, reaching the health facility and
      receiving treatment. STUDY DESIGN: Quasi-experimental study. METHODS: Multistage
      random sampling was used to select 540 villages, from which 1200 women who
      reported obstetric complications in March-April 2010 were interviewed. RESULTS:
      The median time taken to make the decision to access health care was
      significantly lower in the intervention areas compared with the control areas (80
      vs 90 min). In addition, the median time taken to reach the health facility was
      significantly lower in the intervention areas compared with the control areas
      (110 vs 135 min). However, no difference was found in the median time taken to
      receive treatment. Multiple linear regressions demonstrated that the community
      intervention significantly reduced decision making and time taken to reach the
      health facility when accessing EmOC in rural Bangladesh. However, for women
      experiencing haemorrhage, the delays were longer in the intervention areas.
      Protective factors against delayed decision making included access to television,
      previous medical exposure, knowledge, life-threatening complications during
      childbirth and use of a primary health facility. Financial constraints and
      traditional perceptions were associated with delayed decision making.
      Complications during labour, use of a motorized vehicle and use of a primary
      health facility were associated with faster access to EmOC, and poverty,
      distance, transportation difficulties and decision made by male guardian were
      associated with slower access to EmOC. CONCLUSIONS: The intervention appeared to
      reduce the time taken to make the decision to access health care and the time
      taken to reach the health facility when accessing EmOC. This study provides
      support for a focus on emergency preparedness for timely referral from the
      community.

PMID- 24721713
TI  - Let's get physical!: Comment on "Physical methods for genetic transformation of
      fungi and yeast" by Ana L. Rivera, Denis Magana-Ortiz, Miguel Gomez-Lim,
      Francisco Fernandez and Achim M. Loske.

PMID- 24721714
TI  - Cell jamming: collective invasion of mesenchymal tumor cells imposed by tissue
      confinement.
AB  - BACKGROUND: Cancer invasion is a multi-step process which coordinates
      interactions between tumor cells with mechanotransduction towards the surrounding
      matrix, resulting in distinct cancer invasion strategies. Defined by context,
      mesenchymal tumors, including melanoma and fibrosarcoma, develop either single
      cell or collective invasion modes, however, the mechanical and molecular programs
      underlying such plasticity of mesenchymal invasion programs remain unclear.
      METHODS: To test how tissue anatomy determines invasion mode, spheroids of MV3
      melanoma and HT1080 fibrosarcoma cells were embedded into 3D collagen matrices of
      varying density and stiffness and analyzed for migration type and efficacy with
      matrix metalloproteinase (MMP)-dependent collagen degradation enabled or
      pharmacologically inhibited. RESULTS: With increasing collagen density and
      dependent on proteolytic collagen breakdown and track clearance, but independent
      of matrix stiffness, cells switched from single-cell to collective invasion
      modes. Conversion to collective invasion included gain of cell-to-cell junctions,
      supracellular polarization and joint guidance along migration tracks.
      CONCLUSIONS: The density of the extracellulair matrix (ECM) determines the
      invasion mode of mesenchymal tumor cells. Whereas fibrillar, high porosity ECM
      enables single-cell dissemination, dense matrix induces cell-cell interaction,
      leader-follower cell behavior and collective migration as an obligate protease
      dependent process. GENERAL SIGNIFICANCE: These findings establish plasticity of
      cancer invasion programs in response to ECM porosity and confinement, thereby
      recapitulating invasion patterns of mesenchymal tumors in vivo. The conversion to
      collective invasion with increasing ECM confinement supports the concept of cell
      jamming as a guiding principle for melanoma and fibrosarcoma cells into dense
      tissue. This article is part of a Special Issue entitled Matrix-mediated cell
      behaviour and properties.

PMID- 24721715
TI  - Distinct requirements for beta-catenin in pancreatic epithelial growth and
      patterning.
AB  - Pancreatic exocrine and endocrine lineages arise from multipotent pancreatic
      progenitor cells (MPCs). Exploiting the mechanisms that govern expansion and
      differentiation of these cells could enhance efforts to generate beta-cells from
      stem cells. Although our prior work indicates that the canonical Wnt signaling
      component beta-catenin is required qualitatively for exocrine acinar but not
      endocrine development, precisely how this requirement plays out at the level of
      MPCs and their lineage-restricted progeny is unknown. In addition, the
      contribution of beta-catenin function to beta-cell development remains
      controversial. To resolve the potential roles of beta-catenin in development of
      MPCs and beta-cells, we generated pancreas- and pre-endocrine-specific beta
      catenin knockout mice. Pancreas-specific loss of beta-catenin produced not only a
      dramatic reduction in acinar cell numbers, but also a significant reduction in
      beta-cell mass. The loss of beta-cells is due not to a defect in the
      differentiation of endocrine precursors, but instead correlates with an early and
      specific loss of MPCs. In turn, this reflects a novel role for beta-catenin in
      maintaining proximal-distal patterning of the early epithelium, such that distal
      MPCs resort to a proximal, endocrine-competent "trunk" fate when beta-catenin is
      deleted. Moreover, beta-catenin maintains proximal-distal patterning, in part, by
      inhibiting Notch signaling. Subsequently, beta-catenin is required for
      proliferation of both distal and proximal cells, driving overall organ growth. In
      distinguishing two distinct roles for beta-catenin along the route of beta-cell
      development, we suggest that temporally appropriate positive and negative
      manipulation of this molecule could enhance expansion and differentiation of stem
      cell-derived MPCs.

PMID- 24721716
TI  - The PAF1 complex is involved in embryonic epidermal morphogenesis in
      Caenorhabditis elegans.
AB  - The PAF1 complex (PAF1C) is an evolutionarily conserved protein complex involved
      in transcriptional regulation and chromatin remodeling. How the PAF1C is involved
      in animal development is still not well understood. Here, we report that, in the
      nematode Caenorhabditis elegans, the PAF1C is involved in epidermal morphogenesis
      in late embryogenesis. From an RNAi screen we identified the C. elegans ortholog
      of a component of the PAF1C, CTR-9, as a gene whose depletion caused various
      defects during embryonic epidermal morphogenesis, including epidermal cell
      positioning, ventral enclosure and epidermal elongation. RNAi of orthologs of
      other four components of the PAF1C (PAFO-1, LEO-1, CDC-73 and RTFO-1) caused
      similar epidermal defects. In these embryos, whereas the number and cell fate
      determination of epidermal cells were apparently unaffected, their position and
      shape were severely disorganized. PAFO-1::mCherry, mCherry::LEO-1 and GFP::RTFO-1
      driven by the authentic promoters were detected in the nuclei of a wide range of
      cells. Nuclear localization of GFP::RTFO-1 was independent of other PAF1C
      components, while PAFO-1::mCherry and mCherry::LEO-1 dependent on other
      components except RTFO-1. Epidermis-specific expression of mCherry::LEO-1 rescued
      embryonic lethality of the leo-1 deletion mutant. Thus, although the PAF1C is
      universally expressed in C. elegans embryos, its epidermal function is crucial
      for the viability of this animal.

PMID- 24721717
TI  - Critical care paramedics -a missing component for safe interfacility transport in
      the United States.

PMID- 24721719
TI  - Fetal bovine serum and human constitutive androstane receptor: evidence for
      activation of the SV23 splice variant by artemisinin, artemether, and arteether
      in a serum-free cell culture system.
AB  - The naturally occurring SV23 splice variant of human constitutive androstane
      receptor (hCAR-SV23) is activated by di-(2-ethylhexyl)phthalate (DEHP), which is
      detected as a contaminant in fetal bovine serum (FBS). In our initial experiment,
      we compared the effect of dialyzed FBS, charcoal-stripped, dextran-treated FBS
      (CS-FBS), and regular FBS on the basal activity and ligand-activation of hCAR
      SV23 in a cell-based reporter gene assay. In transfected HepG2 cells cultured in
      medium supplemented with 10% FBS, basal hCAR-SV23 activity varied with the type
      of FBS (regular>dialyzed>CS). DEHP increased hCAR-SV23 activity when 10% CS-FBS,
      but not regular FBS or dialyzed FBS, was used. With increasing concentrations (1
      10%) of regular FBS or CS-FBS, hCAR-SV23 basal activity increased, whereas in
      DEHP-treated cells, hCAR-SV23 activity remained similar (regular FBS) or slightly
      increased (CS-FBS). Subsequent experiments identified a serum-free culture
      condition to detect DEHP activation of hCAR-SV23. Under this condition,
      artemisinin, artemether, and arteether increased hCAR-SV23 activity, whereas they
      decreased it in cells cultured in medium supplemented with 10% regular FBS. By
      comparison, FBS increased the basal activity of the wild-type isoform of hCAR
      (hCAR-WT), whereas it did not affect the basal activity of the SV24 splice
      variant (hCAR-SV24) or ligand activation of hCAR-SV24 and hCAR-WT by 6-(4
      chlorophenyl)imidazo[2,1-b][1,3]thiazole-5-carbaldehyde O-(3,4
      dichlorobenzyl)oxime (CITCO). The use of serum-free culture condition was
      suitable for detecting CITCO activation of hCAR-WT and hCAR-SV24. In conclusion,
      FBS leads to erroneous classification of pharmacological ligands of hCAR-SV23 in
      cell-based assays, but investigations on functional ligands of hCAR isoforms can
      be conducted in serum-free culture condition. 

PMID- 24721720
TI  - Life satisfaction and beliefs about self and the world in patients with
      psoriasis: a brief assessment.
AB  - BACKGROUND: Psoriasis is a chronic skin condition that can decrease the level of
      self-esteem, leading to self-devaluation, emotional distress, irrational beliefs
      and discomfort in everyday life. In this study, we aimed to provide a deeper
      understanding of lifestyle satisfaction and to identify the nature and magnitude
      of irrational beliefs in patients with psoriasis. MATERIAL AND METHODS: A two
      year case-control study was carried out between 2010 and 2012. The study enrolled
      100 consecutive patients with psoriasis vulgaris, admitted to a dermatology
      clinic and 101 healthy volunteers with similar demographic characteristics,
      willing to subject themselves to the testing. A series of standardized
      questionnaires were used, including: The Anamnestic Questionnaire, The General
      Attitudes and Beliefs Scale - Short version, The Rosenberg Self-Esteem Scale, The
      Self-Efficacy Scale and The Unconditional Self-Acceptance Questionnaire. RESULTS:
      The tests revealed a strong correlation between the presence of the disease and
      the decrease of subject's satisfaction regarding: body satisfaction, sexual
      satisfaction, social satisfaction, family satisfaction, professional satisfaction
      and satisfaction concerning their own health condition; p<0.01. There were highly
      significant differences with a large effect regarding the level of irrational
      beliefs between the two groups of subjects (p<0.01; f > 0.35). CONCLUSION: The
      focus on psychological impacts of the disease provides important data for a
      holistic approach to patients with psoriasis. Effective cooperation between all
      the parties involved (physicians, family and social network) is necessary to
      improve the patient's psychological status.

PMID- 24721721
TI  - Evaluation of the automated coagulation analyzer CS-5100 and its utility in high
      throughput laboratories.
AB  - BACKGROUND: Automated analyzers are an important component of modern
      laboratories. As a representative of the newest generation of coagulation
      analyzers, the CS-5100 features several technical refinements including a pre
      analytical assessment unit as well as multi-wavelength optical detection units.
      Therefore, the CS-5100 is supposed to rapidly and accurately perform a broad
      panel of coagulation tests. In the current study, the CS-5100 was evaluated
      regarding its precision and practicability in a clinical laboratory setting.
      METHODS: The CS-5100 was evaluated regarding its intra- and inter-assay precision
      using commercially available control samples. RESULTS of patient samples,
      including hemolytic, icteric and lipemic specimens, measured on the CS-5100 were
      compared to reference analyzers, which are used in our accredited laboratory.
      RESULTS: The coefficients of variation, assessed in the intra- and inter-assay
      precision analyses were below 5% representatively for most parameters. RESULTS,
      obtained by the CS-5100 showed predominantly a high comparability to used
      reference analyzers, with correlation coefficients ranging from 0.857 to 0.990.
      Only minor ranged systemic or proportional differences were found in Passing
      Bablok regression between the CS-5100 and reference analyzers regarding most of
      the tested parameters. Lipemic samples had a tendency to deteriorate correlation
      coefficients, but an overall effect of the sample's triglyceride level could be
      ruled out. In a routine setting, the analyzer reached a sample throughput rate of
      160 tests per hour. CONCLUSIONS: The CS-5100 is able to rapidly and precisely
      measure patient samples. No considerable influence on test comparability was
      found for elevated levels of free hemoglobin, bilirubin or triglycerides.

PMID- 24721722
TI  - Bullous pemphigoid in a renal transplant recipient.

PMID- 24721718
TI  - Infection prevention in the emergency department.
AB  - Infection prevention remains a major challenge in emergency care. Acutely ill and
      injured patients seeking evaluation and treatment in the emergency department
      (ED) not only have the potential to spread communicable infectious diseases to
      health care personnel and other patients, but are vulnerable to acquiring new
      infections associated with the care they receive. This article will evaluate
      these risks and review the existing literature for infection prevention practices
      in the ED, ranging from hand hygiene, standard and transmission-based
      precautions, health care personnel vaccination, and environmental controls to
      strategies for preventing health care-associated infections. We will conclude by
      examining what can be done to optimize infection prevention in the ED and
      identify gaps in knowledge where further research is needed. Successful
      implementation of evidence-based practices coupled with innovation of novel
      approaches and technologies tailored specifically to the complex and dynamic
      environment of the ED are the keys to raising the standard for infection
      prevention and patient safety in emergency care. 

PMID- 24721723
TI  - Sarcopenia: an independent predictor of mortality in community-dwelling older
      Korean men.
AB  - BACKGROUND: The concept of sarcopenia has expanded recently to include muscle
      strength or physical performance. We investigated whether the Europe Working
      Group on Sarcopenia in Older People (EWGSOP) definition of sarcopenia predicts
      the risk of all-cause mortality in community-dwelling older adults. METHODS: This
      study included 284 men and 272 women aged 65 and older. The outcome was all-cause
      mortality during the 6-year follow-up period. We defined sarcopenia based on the
      EWGSOP definitions of sarcopenia: height (ht)- or weight (wt)-adjusted
      appendicular skeletal muscle mass (ASM/ht(2) or ASM/wt) assessed by dual-energy x
      ray absorptiometry, leg muscle strength, and short physical performance battery
      test score. RESULTS: During the 6-year follow-up, 40 men and 19 women died. The
      risk of death was 2.99 times and 3.22 times higher in men with sarcopenia
      identified by ASM/ht(2) and ASM/wt, respectively, compared with nonsarcopenic
      men. The hazard ratio for death was 5.37 for men with weak leg muscle strength.
      Men with a low short physical performance battery score had a 3.15 times higher
      risk of death compared with those with high short physical performance battery
      scores, even after adjusting for all covariates. The adjusted hazard ratios for
      EWGSOP-defined sarcopenia were 4.00 for ASM/ht(2) and 6.89 for ASM/wt in men. By
      contrast, sarcopenia defined by these criteria was not associated with a higher
      risk of death in women. CONCLUSIONS: Our data suggest that, in older men, EWGSOP
      defined sarcopenia is related to higher mortality compared with nonsarcopenia
      regardless of the ASM/ht(2) or ASM/wt index. In older women, further studies with
      large sample sizes are needed to assess whether EWGSOP-defined sarcopenia
      increases the mortality risk.

PMID- 24721724
TI  - Amount of care per survivor in young and older patients hospitalized in intensive
      care unit: a retrospective study.
AB  - BACKGROUND: It is unknown whether the amount of care deployed in the intensive
      care unit population divided by the number of survivors, that is, amount of care
      per survivor including the care performed for nonsurvivors, differs between
      patients older and younger than 75 years of age. METHODS: Data were extracted
      from the computerized files of all 2,220 patients admitted in a medical intensive
      care unit between January 2009 and December 2010. Patients >=75 and <75 years old
      were compared. The Omega score per survivor (OMEGA/S) was calculated in both age
      groups by dividing the total amount of Omega points, a score of cumulated care
      load calculated over intensive care unit stay, by the number of survivors in each
      group. RESULTS: OMEGA/S was 26% higher in elderly versus younger patients when
      considering intensive care unit mortality and 40% higher when considering
      hospital mortality. The absence of difference in raw Omega values between the two
      groups implies that OMEGA/S differences were related to differences in mortality
      rate. Simplified Acute Physiology Score II (without age-related points) strata
      analysis (<20, 20-39, 40-59, 60-79, and >=80) showed that OMEGA/S in the elderly
      patients was significantly higher in the first three Simplified Acute Physiology
      Score II strata only. When calculating by main diagnosis categories, a major
      increase in the difference of OMEGA/S between elderly and younger patients was
      observed in cardiac arrest patients due to a major difference in mortality rate.
      CONCLUSIONS: Elderly patients required a significantly higher care load per
      survivor in comparison to younger patients. This excess was mainly due to
      patients with low initial severity.

PMID- 24721726
TI  - New insights toward the transcriptional engineering of proanthocyanidin
      biosynthesis.
AB  - Flavonoids are secondary metabolites that play important roles throughout the
      plant life cycle and have potential human health beneficial properties.
      Flavonols, anthocyanins and proanthocyanidins (PAs or condensed tannins) are the
      three main class of flavonoids found in Arabidopsis thaliana. We have previously
      shown that PA biosynthesis (occurring exclusively in seeds) involves the
      transcriptional activity of four different ternary protein complexes composed of
      different R2R3-MYB and bHLH factors together with TRANSPARENT TESTA GLABRA 1
      (TTG1), a WD repeat containing protein. We have also identified their direct
      targets, the late biosynthetic genes. In this study, we have further investigated
      the transcriptional capacity of the MBW complexes through transactivation assays
      in moss protoplast and overexpression in Arabidopsis siliques. Results provide
      new information for biotechnological engineering of PA biosynthesis, as well as
      new insights into the elucidation of the mechanisms that govern the interactions
      between MBW complexes and the DNA motifs they can target.

PMID- 24721725
TI  - Increases and decreases in drug use attributed to housing status among street
      involved youth in a Canadian setting.
AB  - BACKGROUND: Among a cohort of drug-using street-involved youth, we sought to
      identify the prevalence of reporting increases and decreases in illicit drug use
      due to their current housing status and to identify factors associated with
      reporting these changes. FINDINGS: This longitudinal study was based on data
      collected between June 2008 and May 2012 from a prospective cohort of street
      involved youth aged 14-26 in Vancouver, Canada. At semi-annual study follow-up
      visits, youth were asked if their drug use was affected by their housing status.
      Using generalized estimating equations, we identified factors associated with
      perceived increases and decreases in drug use attributed to housing status. Among
      our sample of 536 participants at baseline, 164 (31%) youth reported increasing
      their drug use due to their housing situation and 71 (13%) reported decreasing
      their drug use. In multivariate analysis, factors that were positively associated
      with perceived increases in drug use attributed to housing status included the
      following: being homeless, engaging in sex work and drug dealing. Regular
      employment was negatively associated with increasing drug use due to housing
      status. Among those who reported decreasing their drug use, only homelessness was
      significant in bivariate analysis. CONCLUSION: Perceived changes in drug use due
      to housing status were relatively common in this setting and were associated with
      being homeless and, among those who increased their drug use, engaging in risky
      income generation activities. These findings suggest that structural factors,
      particularly housing and economic opportunities, may be crucial interventions for
      reducing or limiting drug use among street-involved youth.

PMID- 24721727
TI  - Synthesis and biological evaluation of 2,3-diaryl isoquinolinone derivatives as
      anti-breast cancer agents targeting ERalpha and VEGFR-2.
AB  - The estrogen receptor alpha is recognized as important pharmaceutical target for
      breast cancer therapy, and vascular endothelial growth factor receptors (VEGFRs)
      play important roles in tumor angiogenesis including breast cancer. A series of
      2,3-diaryl isoquinolinone derivatives were designed and synthesized targeting
      both estrogen receptor alpha (ERalpha) and VEGFR-2. Bioactivity evaluation showed
      that compounds 7c, 7d and 7f exhibited significant anti-proliferative and anti
      angiogenesis activities via ERalpha and VEGFR-2 dependent mechanisms.

PMID- 24721728
TI  - Comparison of 2 synthetically generated recombinant prions.
AB  - Prion is a protein-conformation-based infectious agent causing fatal
      neurodegenerative diseases in humans and animals. Our previous studies revealed
      that in the presence of cofactors, infectious prions can be synthetically
      generated in vitro with bacterially expressed recombinant prion protein (PrP).
      Once initiated, the recombinant prion is able to propagate indefinitely via
      serial protein misfolding cyclic amplification (sPMCA). In this study, we
      compared 2 separately initiated recombinant prions. Our results showed that these
      2 recombinant prions had distinct biochemical properties and caused different
      patterns of spongiosis and PrP deposition in inoculated mice. Our findings
      indicate that various recombinant prions can be initiated in vitro and potential
      reasons for this variability are discussed. 

PMID- 24721729
TI  - Anomalous quantized conductance in a half-metal/topological superconductor/half
      metal junction.
AB  - The composite topological superconductor (TS), which is made of one-dimensional
      spin-orbit coupled nanowire with proximity-induced superconductivity from an s
      wave superconductor, is not a pure p-wave superconductor, but has a suppressed s
      wave pairing. We calculate the conductance spectrum of a half-metal/TS/half-metal
      junction in order to probe the pairing states and the spin texture of the p-wave
      pairing. It is found that, besides the regular quantized conductance peak
      contributed by Majorana fermions (MFs) when the half-metal magnetization is
      parallel to the MF spin, an anomalous quantized conductance peak exists when they
      are almost antiparallel. The physical origin is the MF-assisted local Andreev
      reflection to condense s-wave pairings. The anomalous quantized conductance is
      also confirmed by the Kitaev's p-wave model with a nonzero s-wave pairing. The
      findings might provide a new way to find the MF. 

PMID- 24721730
TI  - In vivo evidence for mTORC2-mediated actin cytoskeleton rearrangement in neurons.
AB  - The mammalian target of rapamycin (mTOR) assembles into two distinct multi
      protein complexes called mTORC1 and mTORC2. While mTORC1 controls the signaling
      pathways important for cell growth, the physiological function of mTORC2 is only
      partially known. Here we comment on recent work on gene-targeted mice lacking
      mTORC2 in the cerebellum or the hippocampus that provided strong evidence that
      mTORC2 plays an important role in neuron morphology and synapse function. We
      discuss that this phenotype might be based on the perturbed regulation of the
      actin cytoskeleton and the lack of activation of several PKC isoforms. The fact
      that PKC isoforms and their targets have been implicated in neurological disease
      including spinocerebellar ataxia and that they have been shown to affect learning
      and memory, suggests that aberration of mTORC2 signaling might be involved in
      diseases of the brain. 

PMID- 24721731
TI  - Gradual recruitment and selective clearing generate germ plasm aggregates in the
      zebrafish embryo.
AB  - Determination of primordial germ cells (PGCs) is one of the earliest decisions in
      animal embryogenesis. In many species, PGCs are determined through maternally
      inherited germ plasm ribonucleoparticles (RNPs). In zebrafish, these are
      transmitted during oogenesis as dispersed RNPs, which after fertilization
      multimerize and become recruited as large aggregates at furrows for the first and
      second cell cycles. Here, we show that the number of recruited germ plasm RNPs is
      halved every cell cycle. We also show that germ plasm RNPs are recruited during
      the third cell cycle, but only transiently. Our data support a mechanism in which
      systematic local gathering of germ plasm RNPs during cytokinesis and threshold
      dependent clearing contribute to forming germ plasm aggregates with the highest
      RNP number and germ cell-inducing potential. 

PMID- 24721732
TI  - Differential effects of prenatal chronic high-decibel noise and music exposure on
      the excitatory and inhibitory synaptic components of the auditory cortex analog
      in developing chicks (Gallus gallus domesticus).
AB  - Proper development of the auditory cortex depends on early acoustic experience
      that modulates the balance between excitatory and inhibitory (E/I) circuits. In
      the present social and occupational environment exposure to chronic loud sound in
      the form of occupational or recreational noise, is becoming inevitable. This
      could especially disrupt the functional auditory cortex development leading to
      altered processing of complex sound and hearing impairment. Here we report the
      effects of prenatal chronic loud sound (110-dB sound pressure level (SPL))
      exposure (rhythmic [music] and arrhythmic [noise] forms) on the molecular
      components involved in regulation of the E/I balance in the developing auditory
      cortex analog/Field L (AuL) in domestic chicks. Noise exposure at 110-dB SPL
      significantly enhanced the E/I ratio (increased expression of AMPA receptor GluR2
      subunit and glutamate with decreased expression of GABA(A) receptor gamma 2
      subunit and GABA), whereas loud music exposure maintained the E/I ratio.
      Expressions of markers of synaptogenesis, synaptic stability and plasticity i.e.,
      synaptophysin, PSD-95 and gephyrin were reduced with noise but increased with
      music exposure. Thus our results showed differential effects of prenatal chronic
      loud noise and music exposures on the E/I balance and synaptic function and
      stability in the developing auditory cortex. Loud music exposure showed an
      overall enrichment effect whereas loud noise-induced significant alterations in
      E/I balance could later impact the auditory function and associated cognitive
      behavior. 

PMID- 24721733
TI  - Catestatin and orexin-A neuronal signals alter feeding habits in relation to
      hibernating states.
AB  - Hibernation is a physiological state that by putting vital biological processes
      at rest enables mammals to protect all organs, especially the brain against
      ischemic insults and reperfusion injuries. Earlier studies have highlighted the
      role of hypothalamic (HTH) sites like the periventricular nucleus (Pe) toward
      sleep-wake and cardiovascular activities of hibernators. In the present work,
      infusions of Pe with the orexigenic neuropeptide orexin-A (ORX-A) or the novel
      anti-obesity sympathoinhibitory neuroactive peptide catestatin (CST) have been
      correlated to differing feeding and motor behaviors in the facultative
      hibernating hamster Mesocricetus auratus. Behavioral observations showed that
      treatment with CST provided an anti-obesity activity via the reduction of food
      intake and body weight for all hibernating states, while ORX-A promoted
      orexigenic events during mainly the entrance phase. Moreover, hamsters treated
      with this neuropeptide during the entrance and the arousal hypertensive phases
      also featured elevated ORX 2 receptor (ORX2R) levels in the third layer of the
      parietal cortex and lateral HTH (LH), areas involved with feeding, motor plus
      sleep-wake rhythms. Conversely, ORX-A down-regulated ORX2Rs in the ventromedial
      (VMH) and supraoptic (SO) HTH nuclei that are associated with anorexigenic
      effects. Even CST induced mixed ORX2R expression patterns in mostly HTH areas
      like the evident down-regulation in LH along with the up-regulation in VMH and
      SO. Overall treatments, especially ORX-A+CST led to reduced neurodegenerative
      phenomena in HTH supporting their importance together with ORX2Rs in preserving
      hemodynamic activities, feeding and sleep-wake rhythms of this diencephalic
      station, which may supply useful therapeutic indications for treating
      cardiovascular disturbances linked with brain dysfunctions. 

PMID- 24721734
TI  - From precursors to myelinating oligodendrocytes: contribution of intrinsic and
      extrinsic factors to white matter plasticity in the adult brain.
AB  - Oligodendrocyte precursor cells (OPC) are glial cells that metamorphose into
      myelinating oligodendrocytes during embryogenesis and early stages of post-natal
      life. OPCs continue to divide throughout adulthood and some eventually
      differentiate into oligodendrocytes in response to demyelinating lesions. There
      is growing evidence that OPCs are also involved in activity-driven de novo
      myelination of previously unmyelinated axons and myelin remodeling in adulthood.
      In this review, we summarize the interwoven factors and cascades that promote the
      activation, recruitment and differentiation of OPCs into myelinating
      oligodendrocytes in the adult brain based mostly on results found in the study of
      demyelinating diseases. The goal of the review was to draw a complete picture of
      the transformation of OPCs into mature oligodendrocytes to facilitate the study
      of this transformation in both the normal and diseased adult brain. 

PMID- 24721735
TI  - Looking back, to go forward.

PMID- 24721736
TI  - 14-3-3 and beta-catenin are secreted on extracellular vesicles to activate the
      oncogenic Wnt pathway.
AB  - Aberrant activation of the canonical Wnt signal transduction pathway is involved
      in a large number of human diseases. beta-catenin, the key effector protein of
      the canonical Wnt pathway, functions in the nucleus with T-cell factor/lymphoid
      enhancer factor (TCF/LEF) to activate expression of Wnt target genes. Here we
      show that members of the 14-3-3 protein family bind disheveled-2 (Dvl-2) and
      glycogen synthase-3beta (GSK-3beta) to attenuate the interaction between GSK
      3beta and beta-catenin. Importantly, 14-3-3 and beta-catenin form "bleb-like"
      structures and are secreted via extracellular vesicles to induce Wnt signaling
      activity in target cells. Our data suggest a novel way of transducing the
      oncogenic Wnt signal in which beta-catenin is regulated by 14-3-3zeta through the
      formation of "oncosomes" that contain both the 14-3-3 and beta-catenin proteins.

PMID- 24721737
TI  - Perceived neighbourhood environmental attributes associated with adults'
      recreational walking: IPEN Adult study in 12 countries.
AB  - This study examined the strength and shape of associations between perceived
      environmental attributes and adults' recreational walking, using data collected
      from 13,745 adult participants in 12 countries. Perceived residential density,
      land use mix, street connectivity, aesthetics, safety from crime, and proximity
      to parks were linearly associated with recreational walking, while curvilinear
      associations were found for residential density, land use mix, and aesthetics.
      The observed associations were consistent across countries, except for
      aesthetics. Using data collected from environmentally diverse countries, this
      study confirmed findings from prior single-country studies. Present findings
      suggest that similar environmental attributes are associated with recreational
      walking internationally. 

PMID- 24721738
TI  - Place-based stressors associated with industry and air pollution.
AB  - Exposure to air pollution and its sources is increasingly viewed as a
      psychosocial stress, however its nature is not understood. This article explores
      the role of the concept of place on risk perception and community stress within
      data collected from eight focus groups in Philadelphia, USA. Discussions focused
      on air pollution, a nearby oil refinery, health, and a proposal for air
      monitoring. We present a framework of place-based elements of risk perception
      that includes place identity, stigma and social control. Our findings indicate
      that air pollution contributes to physical and psychosocial conditions that act
      as community-level social stressors. Findings also suggest that programs which
      seek to change behaviors and gather or spread information on issues such as
      pollution and other environmental concerns will be challenged unless they
      directly address: (1) the public's identification with a place or industry, (2)
      immediate environmental stressors such as abandonment, waste and odors, and (3)
      public perceptions of lack of social control and fear of displacement. 

PMID- 24721739
TI  - Body mass index and biliary tract disease: a systematic review and meta-analysis
      of prospective studies.
AB  - OBJECTIVE: To evaluate the association between body mass index (BMI, kg/m(2)) and
      incidence of biliary tract disease. METHODS: We performed a systematic review and
      a meta-analysis of prospective studies by searching the database of PubMed and
      EMBASE published up to December 31, 2013. Outcome of interest was disease of
      biliary tract system (gallbladder, extrahepatic bile duct and Ampullar of Vater).
      We used a random-effects model to combine the study-specific relative risks (RRs)
      and 95% confidence intervals (95% CIs) from 22 prospective studies. We examined
      whether BMI was associated with a higher risk of biliary tract disease in a
      combined analysis. RESULTS: The positive association was stronger for non-cancer
      biliary tract disease than biliary tract cancer; combined RRs (95% CIs) comparing
      the top with bottom categories were 1.40 (1.15-1.65) for biliary tract cancer and
      2.75 (2.35-3.15) for non-cancer biliary tract disease (P for difference<0.001).
      For non-cancer biliary tract disease, combined RRs (95% CIs) comparing the top
      with bottom categories were 3.21 (2.48-3.93) for women and 2.01 (1.66-2.37) for
      men (P for difference=0.04). CONCLUSION: Obesity is associated with higher risks
      of biliary tract cancer and, to a greater extent, non-cancer biliary tract
      disease.

PMID- 24721740
TI  - Neutrophilic disease of the skin and intestines after ipilimumab treatment for
      malignant melanoma - simultaneous occurrence of pyoderma gangrenosum and colitis.

PMID- 24721743
TI  - Development in self-reported arm-lymphedema in Danish women treated for early
      stage breast cancer in 2005 and 2006--a nationwide follow-up study.
AB  - The main purpose of this nationwide follow-up study was to examine the
      development of self-reported lymphedema in the population of women with early
      stage breast cancer in Denmark. In 2008 and 2012 two identical questionnaires
      were sent to the women aged 18-70 years treated for unilateral primary breast
      cancer in 2005 and 2006. 2293 women (87%) reported on lymphedema in 2008 and
      2012. Overall 37% reported lymphedema in 2008 while 31% reported lymphedema in
      2012 and severity of symptoms decreased. 50% of women treated with SLNB and
      reporting lymphedema in 2008 did not report symptoms by 2012 in contrast to 30%
      treated with ALND. However, 19% of women treated with ALND and not reporting
      lymphedema in 2008 had developed lymphedema by 2012. In conclusion lymphedema
      remains a frequent problem, years after treatment for breast cancer, though,
      number of women reporting lymphedema and overall severity of symptoms decreased.

PMID- 24721742
TI  - Response to the article by Thill et al.: "The Central-European SentiMag study:
      sentinel lymph node biopsy with supermagnetic iron oxide (SPIO) vs.
      radioisotope". The Breast 2014.

PMID- 24721741
TI  - The collective therapeutic potential of cerebral ketone metabolism in traumatic
      brain injury.
AB  - The postinjury period of glucose metabolic depression is accompanied by adenosine
      triphosphate decreases, increased flux of glucose through the pentose phosphate
      pathway, free radical production, activation of poly-ADP ribose polymerase via
      DNA damage, and inhibition of glyceraldehyde dehydrogenase (a key glycolytic
      enzyme) via depletion of the cytosolic NAD pool. Under these post-brain injury
      conditions of impaired glycolytic metabolism, glucose becomes a less favorable
      energy substrate. Ketone bodies are the only known natural alternative substrate
      to glucose for cerebral energy metabolism. While it has been demonstrated that
      other fuels (pyruvate, lactate, and acetyl-L-carnitine) can be metabolized by the
      brain, ketones are the only endogenous fuel that can contribute significantly to
      cerebral metabolism. Preclinical studies employing both pre- and postinjury
      implementation of the ketogenic diet have demonstrated improved structural and
      functional outcome in traumatic brain injury (TBI) models, mild TBI/concussion
      models, and spinal cord injury. Further clinical studies are required to
      determine the optimal method to induce cerebral ketone metabolism in the
      postinjury brain, and to validate the neuroprotective benefits of ketogenic
      therapy in humans. 

PMID- 24721744
TI  - Head and neck sarcomas: the UCLA experience.
AB  - PURPOSE: To profile the clinical presentation, subtype distribution, and
      treatment results of sarcomas of the head and neck at a single tertiary academic
      center over an 11-year period. MATERIALS AND METHODS: A retrospective review was
      performed by examining the records and reviewing the pathology of 186 patients
      with head and neck sarcomas treated at UCLA Medical Center from 2000 to 2011.
      RESULTS: The mean age of the study population was 49 +/- 22 years. 58% of the
      patients were male and 42% were female. Median duration of follow-up for the
      entire group was 18.5 months. The most common presenting symptom was a mass
      lesion in 59.9% of patients. The nasal cavity/sinus was the most common
      presenting site seen in 22% of patients. Solitary fibrous
      tumor/hemangiopericytoma was the most common subtype. 15% of patients had
      evidence of prior radiation exposure. 26.3% of tumors were greater than 5 cm and
      35.5% were high-grade. Margins were positive in 31.2% of patients. Lymph node
      metastasis was rare at 6.5%. Perineural invasion was identified in 6.5%. Among
      all subtypes, 5-year recurrence-free survival and overall survival were 50% and
      49%, respectively. Multivariate analysis demonstrated that grade and margin
      status were predictors of recurrence-free survival while grade and age affected
      overall survival. CONCLUSIONS: Head and neck sarcomas are a rare entity
      frequently presenting as a mass lesion. In our series, lesions tended to be high
      grade with a significant portion of surgical specimens having positive margins.
      Grade and margin status were the most important predictors of survival.

PMID- 24721745
TI  - Epidermoid cyst of an intrapancreatic accessory spleen: a case report and
      literature review.
AB  - BACKGROUND: An epidermoid cyst in an intrapancreatic accessory spleen is a rare
      lesion. Despite advances in radiologic techniques, in most cases it has been
      diagnosed preoperatively as a possible pancreatic neoplasm. CASE PRESENTATION:
      Herein, we present a 63-year-old Caucasian woman, diagnosed preoperatively with
      enhanced-contrast abdominal computed tomography, as having a potential cystic
      tumor in the tail of the pancreas. The patient underwent a distal pancreatectomy
      and splenectomy, and the histological examination revealed the presence of an
      epidermoid cyst of an accessory intrapancreatic spleen. CONCLUSIONS: Familiarity
      with the imaging features, the clinical presentation and the location of the cyst
      are important to consider if this rare entity is to be included in the
      differential diagnosis of cystic neoplasms of the pancreas.

PMID- 24721746
TI  - Review: higher vitamin D status and supplementation may be associated with risks.
AB  - The prevalence of low vitamin D levels and associated risks has led to an
      increase in supplementation. However, a "U-shaped" relationship has been
      suggested between vitamin D status and adverse effects, with risks observed both
      in low and high levels. While risks associated with low levels of vitamin D have
      been extensively studied, the risks of higher levels of vitamin D have not been
      as widely circulated. We sought to describe key observed adverse risks with
      vitamin D supplementation and higher serum 25(OH)-D levels in healthy adult
      populations. 

PMID- 24721748
TI  - Grandparenting Roles and Volunteer Activity.
AB  - OBJECTIVES: We examine whether grandparenting roles are related to formal
      volunteering among older adults. METHOD: Logistic regression is used to examine
      the likelihood of volunteering based on grandchild care using data from the 2004
      wave of the Health and Retirement Study (n = 13,785). Longitudinal analyses
      utilize treatment effects models to examine changes in volunteering for
      grandparents who begin nonresidential grandchild care between the 2004 and 2008
      waves (n = 10,811). RESULTS: Results show that grandparents raising coresidential
      grandchildren have lower odds of volunteering than grandparents providing no
      regular grandchild care. However, grandparents who provide nonresidential
      grandchild care are more likely to volunteer than grandparents not providing
      grandchild care and those raising a coresidential grandchild. Grandparents who
      provide nonresidential care for grandchildren engage in more volunteering before
      assuming grandchild care, and their volunteerism increases after becoming a
      caregiver for a grandchild. DISCUSSION: Consistent with resource theory and the
      accumulation of roles, providing nonresidential grandchild care may draw
      grandparents into formal volunteer activity. The lower human capital resources
      evidenced by grandparents raising coresidential grandchildren may play a role in
      their lower likelihood of formal volunteering.

PMID- 24721749
TI  - A man with a mass in the thigh.

PMID- 24721747
TI  - Methylated TRF2 associates with the nuclear matrix and serves as a potential
      biomarker for cellular senescence.
AB  - Methylation of N-terminal arginines of the shelterin component TRF2 is important
      for cellular proliferation. While TRF2 is found at telomeres, where it plays an
      essential role in maintaining telomere integrity, little is known about the
      cellular localization of methylated TRF2. Here we report that the majority of
      methylated TRF2 is resistant to extraction by high salt buffer and DNase I
      treatment, indicating that methylated TRF2 is tightly associated with the nuclear
      matrix. We show that methylated TRF2 drastically alters its nuclear staining as
      normal human primary fibroblast cells approach and enter replicative senescence.
      This altered nuclear staining, which is found to be overwhelmingly associated
      with misshapen nuclei and abnormal nuclear matrix folds, can be suppressed by
      hTERT and it is barely detectable in transformed and cancer cell lines. We find
      that dysfunctional telomeres and DNA damage, both of which are potent inducers of
      cellular senescence, promote the altered nuclear staining of methylated TRF2,
      which is dependent upon the ATM-mediated DNA damage response. Collectively, these
      results suggest that the altered nuclear staining of methylated TRF2 may
      represent ATM-mediated nuclear structural alteration associated with cellular
      senescence. Our data further imply that methylated TRF2 can serve as a potential
      biomarker for cellular senescence. 

PMID- 24721750
TI  - Staying ahead of getting behind: reflections on "scarcity".

PMID- 24721751
TI  - Time to take periodontitis seriously.

PMID- 24721752
TI  - US jails hold 10 times more mentally ill people than state hospitals, report
      finds.

PMID- 24721753
TI  - Quantitative comparison of hemodynamic parameters from steady and transient CFD
      simulations in cerebral aneurysms with focus on the aneurysm ostium.
AB  - OBJECTIVE: To quantitatively compare hemodynamics simulated with steady-state and
      transient computational fluid dynamics (CFD) simulations in cerebral aneurysms
      with single inflow, with focus at the aneurysm ostium. METHODS: Transient and
      steady-state CFD simulations were performed in 10 cerebral aneurysms.
      Distributions and average values for pressure, helicity, vorticity, and velocity
      were qualitatively compared at proximal and distal parent artery locations, at
      the ostium plane, and in the aneurysm, and scaling factors between the two kinds
      of simulations were determined. Relative inflow and outflow areas at the ostium
      were compared, as were average inflow and outflow velocities. In addition, values
      for the pressure-loss coefficient (PLC), a recently introduced parameter to
      assess aneurysm rupture risk, were compared for both kinds of simulation.
      RESULTS: Distributions of hemodynamic parameters had a similar shape but were
      lower for transient than for steady-state simulations. Averaged scaling factors
      over cases and anatomical locations showed differences for hemodynamic parameters
      (0.485 +/- 0.01 for pressure, 0.33 +/- 0.02 for helicity, 0.58 +/- 0.06 for
      vorticity and 0.56 +/- 0.04 for velocity). Good agreement between ratios of
      inflow and outflow areas at the aneurysm ostium was obtained (Pearson correlation
      coefficient >0.97, p<0.001) and for the PLC (linear regression slope 0.73 +/-
      0.14, R(2)=0.75). CONCLUSIONS: Steady-state simulations are a quick alternative
      to transient simulation for visualizing and quantifying inflow and outflow areas
      at the aneurysm ostium, potentially of value when planning flow diverter
      treatment and for quantifying the PLC, a potential indicator of aneurysm rupture.

PMID- 24721754
TI  - Is long-term follow-up of adequately coil-occluded ruptured cerebral aneurysms
      always necessary? A single-center study of recurrences after endovascular
      treatment.
AB  - PURPOSE: Aneurysm recurrence following coil occlusion is well recognized.
      However, there is controversy as to how long these patients should be followed up
      after coiling to detect reopening. We aimed to identify the rate of late
      reopening and the risk factors for reopening in a large single-center cohort of
      ruptured aneurysms that appeared adequately occluded at 6 months. We also aimed
      to assess whether rates of recurrence have altered over time with improving coil
      and angiographic technology. METHODS: Patients treated between 1996 and 2010 were
      assessed and those with both 6-month initial and subsequent long-term follow-up
      with either digital subtraction angiography or magnetic resonance angiography
      were included. Aneurysms were stratified by features such as size, neck width,
      anatomical location and time of treatment: 1996-2005 (cohort 1) and 2006-2010
      (cohort 2). ORs for risk of recurrence were calculated for aneurysm features and
      rates of recurrence in each cohort were compared using a chi(2) test. RESULTS:
      437 patients with 458 adequately occluded aneurysms at 6 months had mean long
      term follow-up of 31 months; 57 (12.4%) were large (>= 10 mm) and 104 (22.7%)
      were wide-necked (>4 mm). Nine aneurysms (2%) showed significant late anatomical
      deterioration whereby retreatment was considered or undertaken. The risk was
      greater for large aneurysms (>= 10 mm) (OR 15.61, 95% CI 3.79 to 64.33, p=0.0001)
      or wide-necked aneurysms (>4 mm) (OR 12.70, 95% CI 2.60 to 62.13, p=0.0017). The
      frequency of significant late anatomical deterioration and retreatment was also
      less common in those treated in cohort 2 (p<0.05). No completely occluded
      aneurysm at 6 months demonstrated significant late recurrence. CONCLUSIONS: Most
      aneurysms adequately occluded at 6 months did not show evidence of late
      recurrence. Large and wide-neck aneurysms are, however, at greater risk of later
      recurrence.

PMID- 24721755
TI  - Tailoring platelet inhibition according to multiple electrode aggregometry
      decreases the rate of thrombotic complications after intracranial flow-diverting
      stent implantation.
AB  - BACKGROUND AND PURPOSE: Pretreatment with dual antiaggregant drugs is accepted as
      a standard step in intracranial stent implantation. The aim of this study was to
      determine whether tailored antiaggregant medication based on platelet reactivity
      testing with multiple electrode aggregometry (Multiplate) yields superior
      outcomes after intracranial flow-diverting stent (FDS) implantation compared with
      standard clopidogrel treatment. METHODS: We retrospectively analyzed the
      following data from 100 consecutive patients: endovascular procedure
      characteristics, antiaggregant medications, procedural variables, and
      perioperative complications after FDS implantation for intracranial aneurysm.
      Patients were divided into two groups: uniform treatment with clopidogrel
      (untailored, early phase) and tailored treatment based on the results of
      aggregometry (late phase). Statistical comparisons included the Fisher exact test
      to compare categorical variables between the standard and aggregometry groups and
      the Mann-Whitney U test to compare ADP test values within the aggregometry group
      between groups receiving tailored or untailored treatment. RESULTS: In the
      aggregometry group (68 patients, 71 procedures) there were 17 (25%) clopidogrel
      resistant patients, according to a cut-off value of 468 area under the
      aggregation curve; 12 underwent FDS implantation under tailored antiaggregant
      medication. In the standard treatment group (32 patients, 33 procedures) there
      were 3 (9.1%) spontaneous thrombotic events and 1 (3.3%) technical hemorrhagic
      complication. In the aggregometry group there were 2 (2.8%) spontaneous
      hemorrhagic events and 1 (1.4%) technical ischemic complication. In the
      aggregometry group, thrombotic complications and morbidity were lower than in the
      standard (no test) group (p<0.03). CONCLUSIONS: Tailoring platelet reactivity
      according to multiple electrode aggregometry decreases the rate of thrombotic
      complications after intracranial FDS implantation.

PMID- 24721756
TI  - Severity of leukoaraiosis, leptomeningeal collaterals, and clinical outcomes
      after intra-arterial therapy in patients with acute ischemic stroke.
AB  - BACKGROUND AND PURPOSE: Leukoaraiosis (LA) is defined as ischemic white matter
      lesions associated with increased stroke risk and poor post-stroke outcomes.
      These lesions are likely the result of diffuse angiopathic changes affecting the
      cerebral small vessels. We investigated whether pre-existing LA burden is
      associated with outcomes in patients with large cerebral artery occlusion
      undergoing intra-arterial therapy (IAT) for acute ischemic stroke (AIS). METHODS:
      We analyzed consecutive AIS subjects undergoing IAT from the institutional Get
      With The Guidelines-Stroke database enrolled between January 1, 2007 and June 30,
      2009, who had National Institutes of Health Stroke Scale scores of >= 8, baseline
      diffusion weighted imaging volume <= 100 mL, and evidence of proximal artery
      occlusion (PAO) on pre-IAT computed tomography angiography (CTA). LA volume (LAv)
      was assessed on fluid attenuated inversion recovery MRI using a validated semi
      automated protocol. We used CTA for collateral grade, post-IAT angiogram for
      recanalization status (Thrombolysis in Cerebral Infarction score >= 2b), and the
      24 h head CT for symptomatic intracranial hemorrhage. Logistic regression was
      used to determine independent predictors of 90 day post-stroke good functional
      outcome (modified Rankin Scale score <= 2) and mortality. RESULTS: Increasing LAv
      independently reduced the odds of good collateral grade (OR 0.85, 95% CI 0.73 to
      0.98). Good functional outcome was independently predicted by intravenous tissue
      plasminogen activator use (OR 12.86, 95% CI 2.20 to 76.28), and recanalization
      status (OR 6.94, 95% CI 1.56 to 30.86). Mortality was independently associated
      with recanalization status (OR 0.08, 95% CI 0.01 to 0.51), age (OR 1.08, 95% CI
      1.01 to 1.15), and antecedent use of hypoglycemic agents (OR 6.55, 95% CI 1.58 to
      54.01). CONCLUSIONS: Severity of LA is linked to poor collateral grade in AIS
      patients undergoing IAT for PAO; however, greater LAv appears not to be a
      contraindication for acute intervention.

PMID- 24721757
TI  - Modifying flow in the ACA-ACoA complex: endovascular treatment option for wide
      neck internal carotid artery bifurcation aneurysms.
AB  - BACKGROUND: Treatment of selected wide-neck internal carotid artery (ICA)
      bifurcation aneurysms remains challenging for clip reconstruction and for
      endovascular options. OBJECTIVE: To describe a new endovascular treatment
      technique for wide-neck ICA bifurcation (ICAb) aneurysms. METHODS: We have
      employed a treatment approach that uses both complete proximal occlusion and
      reversal of flow in the ipsilateral A1 segment, using different endovascular
      modalities such as coils, stent-assisted coiling, or flow diverters (FDs) plus
      coiling concomitantly. This endovascular technique may overcome the challenges of
      current treatments and high recanalization rates for coiled ICAb aneurysms.
      RESULTS: We treated four patients in whom we redirected the pre-existing flow in
      the supraclinoid ICA into the ipsilateral A1 and M1 segments, to a new
      unilateral, linear flow from the supraclinoid ICA solely into the ipsilateral M1
      segment. This resulted in the establishment of flow from the contralateral A1
      segment into the ipsilateral A1 segment, allowing supply of only demanding
      perforating arteries on this specific (ipsilateral) segment. This technique was
      not associated with any new neurological deficits or radiographic ischemia. The
      four patients reviewed were all treated using coils. One was treated with a
      standard stent. The other two were treated with a FD. CONCLUSIONS: We found that
      the proposed technique of flow modification can allow for hemodynamic conversion
      of ICAb to 'side-wall' aneurysm. In patients with good collateral flow through
      the anterior communicating complex, this treatment paradigm is safe and
      effective.

PMID- 24721758
TI  - Experimental evidence of Cr magnetic moments at low temperature in Cr2A(A=Al,
      Ge)C.
AB  - From x-ray magnetic circular dichroism experiments performed at low temperature
      on Cr2AlC and Cr2GeC thin films, it is evidenced that Cr atoms carry a net
      magnetic moment in these ternary phases. It is shown that the Cr magnetization of
      the Al-based compound nearly vanished at 100 K in agreement with what has been
      recently observed on bulk. X-ray linear dichroism measurements performed at
      various angles of incidence and temperatures clearly demonstrate the existence of
      a charge ordering along the c axis of the structure of Cr2AlC. All these
      experimental observations support, in part, theoretical calculations claiming
      that Cr dd correlations have to be considered to correctly describe the structure
      and properties of these Cr-based ternary phases. 

PMID- 24721759
TI  - Hormone influence on the spatial regulation of IRT1 expression in iron-deficient
      Arabidopsis thaliana roots.
AB  - The IRON-REGULATED TRANSPORTER1 (IRT1) is the principal importer of soil iron in
      Arabidopsis thaliana. It has a complex intracellular trafficking behavior,
      including continuous cycling between plasma membrane and endosomes. SORTING
      NEXIN1 is required for the recycling of endosome-localized IRT1. In its absence,
      IRT1 is mistargeted for degradation, resulting in reduced plant iron-uptake
      efficiency. Consequently, IRT1 promoter activity gets limited to a specific
      portion of the root. We tested the influence of two hormones known to positively
      affect iron uptake on IRT1 spatial regulation. We found that ethylene treatment
      in wild-type background mimics the effects of the SNX-loss-of-function situation.
      Conversely, auxin splits the IRT1 expression zone and forces it toward the two
      extremities of the root. This shows that IRT1 expression along the root is
      modulated by ethylene-auxin interplay.

PMID- 24721760
TI  - Early Pleistocene aquatic resource use in the Turkana Basin.
AB  - Evidence for the acquisition of nutritionally dense food resources by early
      Pleistocene hominins has implications for both hominin biology and behavior.
      Aquatic fauna may have comprised a source of highly nutritious resources to
      hominins in the Turkana Basin at ~1.95 Ma. Here we employ multiple datasets to
      examine the issue of aquatic resource use in the early Pleistocene. This study
      focuses on four components of aquatic faunal assemblages (1) taxonomic diversity,
      (2) skeletal element proportion, (3) bone fragmentation and (4) bone surface
      modification. These components are used to identify associations between early
      Pleistocene aquatic remains and hominin behavior at the site of FwJj20 in the
      Koobi Fora Fm. (Kenya). We focus on two dominant aquatic species: catfish and
      turtles. Further we suggest that data on aquatic resource availability as well as
      ethnographic examples of aquatic resource use complement our observations on the
      archaeological remains from FwJj20. Aquatic food items provided hominins with a
      valuable nutritional alternative to an exclusively terrestrial resource base. We
      argue that specific advantages afforded by an aquatic alternative to terrestrial
      resources include (1) a probable reduction in required investment of energy
      relative to economic return in the form of nutritionally dense food items, (2) a
      decrease in the technological costs of resource acquisition, and (3) a reduced
      level of inter-specific competition associated with carcass access and an
      associated reduction of predation risk relative to terrestrial sources of food.
      The combined evidence from FwJj20 suggests that aquatic resources may have played
      a substantial role in early Pleistocene diets and these resources may have been
      overlooked in previous interpretations of hominin behavior.

PMID- 24721761
TI  - Feasibility and safety of a new generation of gore septal occluder device in
      children.
AB  - AIM: Transcatheter closure of an ostium secundum atrial septal defect (ASD) is
      now considered the standard care for most of children with the appropriate
      anatomy, and is a relatively well-tolerated procedure to reduce the clinical
      sequelae of ASD, with a low complication rate. METHODS: The present case reports
      describe our clinical experience of the percutaneous closure of a secundum ASD in
      10 children between December 2011 and November 2012, by means of a new generation
      of device, the GORE Septal Occluder device. RESULTS: The implantation was
      successful in all except two cases, the device being properly placed and deployed
      without malposition or embolization in the catheterization laboratory. No
      complications were related to the procedure. The successful implant was confirmed
      and no major adverse events were documented in the following 3-12 months.
      CONCLUSION: The new GORE Septal Occluder device appears to be a feasible, well
      tolerated and successful tool for the closure of an ASD of 15 mm or less in
      childhood.

PMID- 24721763
TI  - CPAC: Energy-efficient data collection through adaptive selection of compression
      algorithms for sensor networks.
AB  - We propose a technique to optimize the energy efficiency of data collection in
      sensor networks by exploiting a selective data compression. To achieve such an
      aim, we need to make optimal decisions regarding two aspects: (1) which sensor
      nodes should execute compression; and (2) which compression algorithm should be
      used by the selected sensor nodes. We formulate this problem into binary integer
      programs, which provide an energy-optimal solution under the given latency
      constraint. Our simulation results show that the optimization algorithm
      significantly reduces the overall network-wide energy consumption for data
      collection. In the environment having a stationary sink from stationary sensor
      nodes, the optimized data collection shows 47% energy savings compared to the
      state-of-the-art collection protocol (CTP). More importantly, we demonstrate that
      our optimized data collection provides the best performance in an intermittent
      network under high interference. In such networks, we found that the selective
      compression for frequent packet retransmissions saves up to 55% energy compared
      to the best known protocol. 

PMID- 24721762
TI  - The proximal promoter of a novel interleukin-8-encoding gene in rainbow trout
      (Oncorhynchus mykiss) is strongly induced by CEBPA, but not NF-kappaB p65.
AB  - Interleukin-8 (IL8) is an immediate-early chemokine that has been well
      characterized in several fish species. Ten IL8 gene variants have already been
      described in rainbow trout, but none of their promoters has structurally been
      defined or functionally characterized in teleost fish. To uncover key factors
      regulating IL8 expression, we intended to functionally characterize an IL8
      promoter from rainbow trout. Incidentally, we isolated a novel IL8 gene variant
      (IL8-G). It is structurally highly similar to the other trout IL8 gene variants
      and its mRNA concentration increased significantly in secondary lymphoid tissues
      after infecting healthy fish with Aeromonas salmonicida. The proximal promoter
      sequence of the IL8-G-encoding gene features in close proximity two consensus
      elements for CEBP attachment. The proximal site overlaps with a NF-kappaB-binding
      site. Cotransfection of an IL8-G promoter-driven reporter gene together with
      vectors expressing various mammalian CEBP or NF-kappaB factors revealed in human
      HEK-293 cells that CEBPA and NF-kappaB p50, but not NF-kappaB p65 activate this
      promoter. The stimulatory effect of NF-kappaB p50 is likely conveyed by
      synergizing with CEBPA. Deletion or mutation of either the distal or the proximal
      CEBP-binding site, respectively, caused a significant decrease in IL8-G promoter
      activation. We confirmed the significance of the CEBPA factor for IL8-G
      expression by comparing the stimulatory capacity of the trout CEBPA and -B
      factors, thereby reducing the evolutionary distance in the inter-species
      expression assays. Similar promoter induction potential and intracellular
      localization of the mammalian and teleostean CEBPA and -B factors suggests their
      functional conservation throughout evolution. 

PMID- 24721764
TI  - Security analysis and improvements of two-factor mutual authentication with key
      agreement in wireless sensor networks.
AB  - User authentication and key management are two important security issues in WSNs
      (Wireless Sensor Networks). In WSNs, for some applications, the user needs to
      obtain real-time data directly from sensors and several user authentication
      schemes have been recently proposed for this case. We found that a two-factor
      mutual authentication scheme with key agreement in WSNs is vulnerable to gateway
      node bypassing attacks and user impersonation attacks using secret data stored in
      sensor nodes or an attacker's own smart card. In this paper, we propose an
      improved scheme to overcome these security weaknesses by storing secret data in
      unique ciphertext form in each node. In addition, our proposed scheme should
      provide not only security, but also efficiency since sensors in a WSN operate
      with resource constraints such as limited power, computation, and storage space.
      Therefore, we also analyze the performance of the proposed scheme by comparing
      its computation and communication costs with those of other schemes. 

PMID- 24721765
TI  - Rhodotorula mucilaginosa, a quorum quenching yeast exhibiting lactonase activity
      isolated from a tropical shoreline.
AB  - Two microbial isolates from a Malaysian shoreline were found to be capable of
      degrading N-acylhomoserine lactones. Both Matrix Assisted Laser Desorption
      Ionization-Time of Flight-Mass Spectrometry and 18S rDNA phylogenetic analyses
      confirmed that these isolates are Rhodotorula mucilaginosa. Quorum quenching
      activities were detected by a series of bioassays and rapid resolution liquid
      chromatography analysis. The isolates were able to degrade various quorum sensing
      molecules namely N-hexanoyl-L-homoserine lactone (C6-HSL), N-(3-oxo-hexanoyl)-L
      homoserine lactone (3-oxo-C6-HSL) and N-(3-hydroxyhexanoyl)-L-homoserine lactone
      (3-hydroxy-C6-HSL). Using a relactonisation assay to verify the quorum quenching
      mechanism, it is confirmed that Rh. mucilaginosa degrades the quorum sensing
      molecules via lactonase activity. To the best of our knowledge, this is the first
      documentation of the fact that Rh. mucilaginosa has activity against a broad
      range of AHLs namely C6-HSL, 3-oxo-C6-HSL and 3-hydroxy-C6-HSL. 

PMID- 24721766
TI  - Window size impact in human activity recognition.
AB  - Signal segmentation is a crucial stage in the activity recognition process;
      however, this has been rarely and vaguely characterized so far. Windowing
      approaches are normally used for segmentation, but no clear consensus exists on
      which window size should be preferably employed. In fact, most designs normally
      rely on figures used in previous works, but with no strict studies that support
      them. Intuitively, decreasing the window size allows for a faster activity
      detection, as well as reduced resources and energy needs. On the contrary, large
      data windows are normally considered for the recognition of complex activities.
      In this work, we present an extensive study to fairly characterize the windowing
      procedure, to determine its impact within the activity recognition process and to
      help clarify some of the habitual assumptions made during the recognition system
      design. To that end, some of the most widely used activity recognition procedures
      are evaluated for a wide range of window sizes and activities. From the
      evaluation, the interval 1-2 s proves to provide the best trade-off between
      recognition speed and accuracy. The study, specifically intended for on-body
      activity recognition systems, further provides designers with a set of guidelines
      devised to facilitate the system definition and configuration according to the
      particular application requirements and target activities. 

PMID- 24721767
TI  - EPCGen2 pseudorandom number generators: analysis of J3Gen.
AB  - This paper analyzes the cryptographic security of J3Gen, a promising pseudo
      random number generator for low-cost passive Radio Frequency Identification
      (RFID) tags. Although J3Gen has been shown to fulfill the randomness criteria set
      by the EPCglobal Gen2 standard and is intended for security applications, we
      describe here two cryptanalytic attacks that question its security claims: (i) a
      probabilistic attack based on solving linear equation systems; and (ii) a
      deterministic attack based on the decimation of the output sequence. Numerical
      results, supported by simulations, show that for the specific recommended values
      of the configurable parameters, a low number of intercepted output bits are
      enough to break J3Gen. We then make some recommendations that address these
      issues. 

PMID- 24721768
TI  - New system for tracking a device for diagnosing scalp skin.
AB  - In scalp skin examinations, it is difficult to find a previously treated region
      on a patient's scalp through images captured by a camera attached to a diagnostic
      device because the zoom lens on camera has a small field of view. Thus, doctors
      manually record the region on a chart or manually mark the region. However, this
      process is slow and inconveniences the patient. Thus, we propose a new system for
      tracking the diagnostic device for the scalp skin of patients. Our research is
      novel in four ways. First, our proposed system consists of two cameras to capture
      the face and the diagnostic device. Second, the user can easily set the position
      of camera to capture the diagnostic device by manually moving a frame to which
      the camera is attached. Third, the position of patient's nostrils and corners of
      the eyes are detected to align the position of his/her head more accurately with
      the recorded position from previous sessions. Fourth, the position of the
      diagnostic device is continuously tracked during the examination through images
      that help detect the position of the color marker attached to the device.
      Experimental results show that our system has a higher performance than
      conventional method. 

PMID- 24721769
TI  - Low-power wearable respiratory sound sensing.
AB  - Building upon the findings from the field of automated recognition of respiratory
      sound patterns, we propose a wearable wireless sensor implementing on-board
      respiratory sound acquisition and classification, to enable continuous monitoring
      of symptoms, such as asthmatic wheezing. Low-power consumption of such a sensor
      is required in order to achieve long autonomy. Considering that the power
      consumption of its radio is kept minimal if transmitting only upon (rare)
      occurrences of wheezing, we focus on optimizing the power consumption of the
      digital signal processor (DSP). Based on a comprehensive review of asthmatic
      wheeze detection algorithms, we analyze the computational complexity of common
      features drawn from short-time Fourier transform (STFT) and decision tree
      classification. Four algorithms were implemented on a low-power TMS320C5505 DSP.
      Their classification accuracies were evaluated on a dataset of prerecorded
      respiratory sounds in two operating scenarios of different detection fidelities.
      The execution times of all algorithms were measured. The best classification
      accuracy of over 92%, while occupying only 2.6% of the DSP's processing time, is
      obtained for the algorithm featuring the time-frequency tracking of shapes of
      crests originating from wheezing, with spectral features modeled using energy. 

PMID- 24721770
TI  - Sensing of scent, fragrance, smell, and odor emissions from biota sources.

PMID- 24721771
TI  - A novel high-sensitivity, low-power, liquid crystal temperature sensor.
AB  - A novel temperature sensor based on nematic liquid crystal permittivity as a
      sensing magnitude, is presented. This sensor consists of a specific micrometric
      structure that gives considerable advantages from other previous related liquid
      crystal (LC) sensors. The analytical study reveals that permittivity change with
      temperature is introduced in a hyperbolic cosine function, increasing the
      sensitivity term considerably. The experimental data has been obtained for ranges
      from -6  degrees C to 100  degrees C. Despite this, following the LC datasheet,
      theoretical ranges from -40  degrees C to 109  degrees C could be achieved. These
      results have revealed maximum sensitivities of 33 mVrms/ degrees C for certain
      temperature ranges; three times more than of most silicon temperature sensors. As
      it was predicted by the analytical study, the micrometric size of the proposed
      structure produces a high output voltage. Moreover the voltage's sensitivity to
      temperature response can be controlled by the applied voltage. This response
      allows temperature measurements to be carried out without any amplification or
      conditioning circuitry, with very low power consumption. 

PMID- 24721772
TI  - Uncertain data clustering-based distance estimation in Wireless Sensor Networks.
AB  - For communication distance estimations in Wireless Sensor Networks (WSNs), the
      RSSI (Received Signal Strength Indicator) value is usually assumed to have a
      linear relationship with the logarithm of the communication distance. However,
      this is not always true in reality because there are always uncertainties in RSSI
      readings due to obstacles, wireless interferences, etc. In this paper, we
      specifically propose a novel RSSI-based communication distance estimation method
      based on the idea of interval data clustering. We first use interval data,
      combined with statistical information of RSSI values, to interpret the
      distribution characteristics of RSSI. We then use interval data hard clustering
      and soft clustering to overcome different levels of RSSI uncertainties,
      respectively. We have used real RSSI measurements to evaluate our communication
      distance estimation method in three representative wireless environments.
      Extensive experimental results show that our communication distance estimation
      method can effectively achieve promising estimation accuracy with high efficiency
      when compared to other state-of-art approaches. 

PMID- 24721773
TI  - Luminescent measurement systems for the investigation of a scramjet inlet
      isolator.
AB  - Scramjets have become a main focus of study for many researchers, due to their
      application as propulsive devices in hypersonic flight. This entails a detailed
      understanding of the fluid mechanics involved to be able to design and operate
      these engines with maximum efficiency even at their off-design conditions. It is
      the objective of the present cold-flow investigation to study and analyse
      experimentally the mechanics of the fluid structures encountered within a generic
      scramjet inlet at M = 5. Traditionally, researchers have to rely on stream-thrust
      analysis, which requires the complex setup of a mass flow meter, a force balance
      and a heat transducer in order to measure inlet-isolator performance.
      Alternatively, the pitot rake could be positioned at inlet-isolator exit plane,
      but this method is intrusive to the flow, and the number of pitot tubes is
      limited by the model size constraint. Thus, this urgent need for a better flow
      diagnostics method is addressed in this paper. Pressure-sensitive paint (PSP) has
      been applied to investigate the flow characteristics on the compression ramp,
      isolator surface and isolator sidewall. Numerous shock-shock interactions, corner
      and shoulder separation regions, as well as shock trains were captured by the
      luminescent system. The performance of the scramjet inlet-isolator has been shown
      to improve when operated in a modest angle of attack. 

PMID- 24721774
TI  - Advances in bio-tactile sensors for minimally invasive surgery using the fibre
      Bragg grating force sensor technique: a survey.
AB  - The large interest in utilising fibre Bragg grating (FBG) strain sensors for
      minimally invasive surgery (MIS) applications to replace conventional electrical
      tactile sensors has grown in the past few years. FBG strain sensors offer the
      advantages of optical fibre sensors, such as high sensitivity, immunity to
      electromagnetic noise, electrical passivity and chemical inertness, but are not
      limited by phase discontinuity or intensity fluctuations. FBG sensors feature a
      wavelength-encoding sensing signal that enables distributed sensing that utilises
      fewer connections. In addition, their flexibility and lightness allow easy
      insertion into needles and catheters, thus enabling localised measurements inside
      tissues and blood. Two types of FBG tactile sensors have been emphasised in the
      literature: single-point and array FBG tactile sensors. This paper describes the
      current design, development and research of the optical fibre tactile techniques
      that are based on FBGs to enhance the performance of MIS procedures in general.
      Providing MIS or microsurgery surgeons with accurate and precise measurements and
      control of the contact forces during tissues manipulation will benefit both
      surgeons and patients. 

PMID- 24721775
TI  - Cytokine-driven loss of plasmacytoid dendritic cell function in chronic
      lymphocytic leukemia.
AB  - Chronic lymphocytic leukemia (CLL) is characterized by the accumulation of
      CD5(+)CD19(+) B cells in the peripheral blood, and in primary and secondary
      lymphoid organs. A major complication associated with CLL is severe recurrent
      infections, which are often fatal. Vulnerability to infection is due to a wide
      variety of immunological defects, yet the initiating events of immunodeficiency
      in CLL are unclear. Using CLL patient samples and a mouse model of CLL, we have
      discovered that plasmacytoid dendritic cells (pDCs), which underpin the activity
      of effector immune cells critical for anti-viral immunity and anti-tumor
      responses, are reduced in number and functionally impaired in progressive CLL. As
      a result, the levels of interferon alpha (IFNalpha) production, a cytokine
      critical for immunity, are markedly reduced. Lower pDC numbers with impaired
      IFNalpha production was due to the decreased expression of FMS-like tyrosine
      kinase 3 receptor (Flt3) and Toll-like receptor 9 (TLR9), respectively. Reduced
      Flt3 expression was reversed using inhibitors of TGF-beta and TNF, an effect
      correlating with a reduction in tumor load. Defects in pDC numbers and function
      offer new insight into mechanisms underpinning the profound immunodeficiency
      affecting CLL patients and provide a potentially novel avenue for restoring
      immunocompetency in CLL. 

PMID- 24721776
TI  - Dual optimization based prostate zonal segmentation in 3D MR images.
AB  - Efficient and accurate segmentation of the prostate and two of its clinically
      meaningful sub-regions: the central gland (CG) and peripheral zone (PZ), from 3D
      MR images, is of great interest in image-guided prostate interventions and
      diagnosis of prostate cancer. In this work, a novel multi-region segmentation
      approach is proposed to simultaneously segment the prostate and its two major sub
      regions from only a single 3D T2-weighted (T2w) MR image, which makes use of the
      prior spatial region consistency and incorporates a customized prostate
      appearance model into the segmentation task. The formulated challenging
      combinatorial optimization problem is solved by means of convex relaxation, for
      which a novel spatially continuous max-flow model is introduced as the dual
      optimization formulation to the studied convex relaxed optimization problem with
      region consistency constraints. The proposed continuous max-flow model derives an
      efficient duality-based algorithm that enjoys numerical advantages and can be
      easily implemented on GPUs. The proposed approach was validated using 18 3D
      prostate T2w MR images with a body-coil and 25 images with an endo-rectal coil.
      Experimental results demonstrate that the proposed method is capable of
      efficiently and accurately extracting both the prostate zones: CG and PZ, and the
      whole prostate gland from the input 3D prostate MR images, with a mean Dice
      similarity coefficient (DSC) of 89.3+/-3.2% for the whole gland (WG), 82.2+/-3.0%
      for the CG, and 69.1+/-6.9% for the PZ in 3D body-coil MR images; 89.2+/-3.3% for
      the WG, 83.0+/-2.4% for the CG, and 70.0+/-6.5% for the PZ in 3D endo-rectal coil
      MR images. In addition, the experiments of intra- and inter-observer variability
      introduced by user initialization indicate a good reproducibility of the proposed
      approach in terms of volume difference (VD) and coefficient-of-variation (CV) of
      DSC. 

PMID- 24721777
TI  - The importance of biopsy in clinically diagnosed metastatic lesions in patients
      with breast cancer.
AB  - BACKGROUND: Receptor status discordance, such as estrogen receptor (ER),
      progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2)
      status between primary breast cancer and metastatic lesions has been reported.
      The aim of this study was to evaluate the biopsy of clinically diagnosed
      metastatic lesions and to determine the changes in hormonal receptor and HER2
      status of the metastatic lesions. METHODS: Sixty-three patients with clinically
      diagnosed metastatic breast cancer underwent an excisional biopsy or core needle
      aspiration guided by computed tomography/ultrasound. ER, PR and HER2 were
      assessed by immunohistochemistry (IHC). RESULTS: A total of 48 metastases (76.2%)
      and nine second primary malignancies (14.3%, seven primary lung cancers and two
      primary pancreatic cancers) were found. The discrepancies between ER, PR and HER2
      status between the primary breast cancer and metastatic lesions were 14.6%, 16.7%
      and 8.3%, respectively. Six lesions (9.5%) were proved benign upon biopsy.
      CONCLUSIONS: The biopsy of clinically suspicious metastatic lesions could
      histologically confirm the diagnosis of metastasis, evaluate discrepancies
      between ER, PR and HER2 status and exclude secondary malignancy, which might
      change the therapeutic strategy for breast cancer patients.

PMID- 24721778
TI  - Dramatic response to radiotherapy combined with vemurafenib. Is vemurafenib a
      radiosensitizer?

PMID- 24721779
TI  - Accuracy of administrative diagnostic data for pathologically confirmed cases of
      Creutzfeldt-Jakob disease in Massachusetts, 2000-2008.
AB  - BACKGROUND: Creutzfeldt-Jakob disease (CJD) is a transmissible disorder that is
      monitored by public health authorities at the state and national levels in the
      United States. Little is known about the current accuracy and concurrence of CJD
      diagnoses across national and state sources of surveillance data. METHODS: Using
      multiple sources, including the National Prion Disease Pathology Surveillance
      Center (NPDPSC) registry, we sought to identify all deceased Massachusetts
      patients with pathologically diagnosed CJD between 2000 and 2008. Pathologically
      verified CJD cases were then matched to their respective records in the
      Massachusetts hospital discharge and death certificate datasets. Using these
      data, we also aimed to estimate the sensitivity and specificity of death
      certificate diagnoses. RESULTS: Death certificate and hospital discharge dataset
      diagnoses of CJD combined accounted for 80% (35 of 44) of pathologically
      confirmed cases. The estimated sensitivity and specificity for death certificate
      diagnoses alone were 71% (27 of 38) and 75% (9 of 12), respectively. CONCLUSIONS:
      Death certificate diagnoses were less sensitive for pathologically confirmed CJD
      than reported previously. Increasing reliance on autopsy over biopsy and an
      expanding spectrum of health care delivery may be responsible for this
      discrepancy. The findings reported here underscore the value of using multiple
      mechanisms in national CJD surveillance.

PMID- 24721781
TI  - Hyper-parallel photonic quantum computation with coupled quantum dots.
AB  - It is well known that a parallel quantum computer is more powerful than a
      classical one. So far, there are some important works about the construction of
      universal quantum logic gates, the key elements in quantum computation. However,
      they are focused on operating on one degree of freedom (DOF) of quantum systems.
      Here, we investigate the possibility of achieving scalable hyper-parallel quantum
      computation based on two DOFs of photon systems. We construct a deterministic
      hyper-controlled-not (hyper-CNOT) gate operating on both the spatial-mode and the
      polarization DOFs of a two-photon system simultaneously, by exploiting the giant
      optical circular birefringence induced by quantum-dot spins in double-sided
      optical microcavities as a result of cavity quantum electrodynamics (QED). This
      hyper-CNOT gate is implemented by manipulating the four qubits in the two DOFs of
      a two-photon system without auxiliary spatial modes or polarization modes. It
      reduces the operation time and the resources consumed in quantum information
      processing, and it is more robust against the photonic dissipation noise,
      compared with the integration of several cascaded CNOT gates in one DOF. 

PMID- 24721780
TI  - Role of the lncRNA-p53 regulatory network in cancer.
AB  - Advances in functional genomics have led to discovery of a large group of
      previous uncharacterized long non-coding RNAs (lncRNAs). Emerging evidence
      indicates that lncRNAs may serve as master gene regulators through various
      mechanisms. Dysregulation of lncRNAs is often associated with a variety of human
      diseases including cancer. Of significant interest, recent studies suggest that
      lncRNAs participate in the p53 tumor suppressor regulatory network. In this
      review, we discuss how lncRNAs serve as p53 regulators or p53 effectors. Further
      characterization of these p53-associated lncRNAs in cancer will provide a better
      understanding of lncRNA-mediated gene regulation in the p53 pathway. As a result,
      lncRNAs may prove to be valuable biomarkers for cancer diagnosis or potential
      targets for cancer therapy. 

PMID- 24721782
TI  - Stem cells: balancing resistance and sensitivity to DNA damage.
AB  - Embryonic stem cells (ESCs) are known to be very sensitive to DNA damage and
      undergo rapid apoptosis even after low-damage doses. By contrast, adult stem
      cells show variable sensitivity to damage. Here we describe the multiple pathways
      that have been proposed to affect the sensitivity of stem cells to damage,
      including proximity to the apoptotic threshold (mitochondrial priming) and the
      p53 signaling pathway, through activation of transcription or direct interaction
      with proapoptotic proteins in the cytoplasm. We also discuss which cellular
      factors might connect mitochondrial priming with pluripotency and the potential
      therapeutic advances that can be achieved by better understanding of the
      molecular mechanisms leading to sensitivity or resistance of embryonic or adult
      stem cells from different tissues. 

PMID- 24721783
TI  - Biodiversity of entomopathogenic nematodes in Italy.
AB  - An investigation was carried out on the distribution and biodiversity of
      steinernematid and heterorhabdtid entomopathogenic nematodes (EPN) in nine
      regions of Italy in the period 1990-2010. More than 2000 samples were collected
      from 580 localities and 133 of them yielded EPN specimens. A mapping of EPN
      distribution in Italy showed 133 indigenous EPN strains belonging to 12 species:
      43 isolates of Heterorhabditis bacteriophora, 1 of H. downesi, 1 of H. megidis,
      51 of Steinernema feltiae, 12 of S. affine, 4 of S. kraussei, 8 of S. apuliae, 5
      of S. ichnusae, 3 of S. carpocapsae, 1 of S. vulcanicum, 3 of Steinernema
      'isolate S.sp.MY7' of 'S. intermedium group' and 1 of S. arenarium.
      Steinernematids are more widespread than heterorhabditids and S. feltiae and H.
      bacteriophora are the most commonly encountered species. Sampling sites were
      grouped into 11 habitats: uncultivated land, orchard, field, sea coast, pinewood,
      broadleaf wood, grasslands, river and lake borders, caves, salt pan and moist
      zones; the soil texture of each site was defined and the preferences of habitat
      and soil texture of each species was assessed. Except for the two dominant
      species, S. feltiae and H. bacteriophora, EPN occurrence tends to be correlated
      with a specific vegetation habitat. Steinernema kraussei, H. downesi and H.
      megidis were collected only in Sicily and three of the species recently described
      - S. apuliae, S. ichnusae and S. vulcanicum - are known only from Italy and seem
      to be endemic. 

PMID- 24721784
TI  - Computer-automated ABCD versus dermatologists with different degrees of
      experience in dermoscopy.
AB  - BACKGROUND: Dermoscopy is a very useful and non-invasive technique for in vivo
      observation and preoperative diagnosis of pigmented skin lesions (PSLs) inasmuch
      as it enables analysis of surface and subsurface structures that are not
      discernible to the naked eye. METHODS: The authors used the ABCD rule of
      dermoscopy to test the accuracy of melanoma diagnosis with respect to a panel of
      165 PSLs and the intra- and inter-observer diagnostic agreement obtained between
      three dermatologists with different degrees of experience, one General
      Practitioner and a DDA for computer-assisted diagnosis (Nevuscreen((r)), Arke
      s.a.s., Avezzano, Italy). RESULTS: 165 Pigmented Skin Lesions from 165 patients
      were selected. Histopathological examination revealed 132 benign melanocytic skin
      lesions and 33 melanomas. The kappa statistic, sensitivity, specificity and
      predictive positive and negative values were calculated to measure agreement
      between all the human observers and in comparison with the automated DDA.
      CONCLUSION: Our results revealed poor reproducibility of the semi-quantitative
      algorithm devised by Stolz et al. independently of observers' experience in
      dermoscopy. Nevuscreen((r)) (Arke s.a.s., Avezzano, Italy) proved to be 'user
      friendly' to all observers, thus enabling a more critical evaluation of each
      lesion and representing a helpful tool for clinicians without significant
      experience in dermoscopy in improving and achieving more accurate diagnosis of
      PSLs.

PMID- 24721785
TI  - Malignant melanoma arising in the skin lesions of Nagashima-type palmoplantar
      keratosis.

PMID- 24721786
TI  - Prostate cancer-derived CCN3 induces M2 macrophage infiltration and contributes
      to angiogenesis in prostate cancer microenvironment.
AB  - Tumor-associated macrophages (TAMs) are M2-polarized macrophages that infiltrate
      the tumor microenvironment and promote tumorigenesis. However, the mechanisms by
      which TAMs modulate prostate cancer (PCa) growth are poorly understood. Here, we
      found that expression of Nephroblastoma Overexpressed (NOV/CCN3) is upregulated
      in PCa cells and correlated with M2 macrophage infiltration. RAW264.7 macrophage
      migration was induced by conditioned media (CM) from various PCa cells in
      proportion to the cellular level of CCN3 expression and was inhibited by an anti
      CCN3 neutralizing antibody. CCN3 and PCaCM treatment skewed RAW264.7 cell
      differentiation from an M1 phenotype to an M2 phenotype. PCa-derived CCN3 induced
      focal adhesion kinase (FAK)/Akt/NF-kappaB signaling in RAW264.7 cells, which
      resulted in VEGF expression and subsequently increased tube formation in
      endothelial progenitor cells. Finally, PCa-secreted CCN3 stimulated RAW264.7
      cells and promoted angiogenesis in the chick chorioallantoic membrane assay
      (CAM), and increased tumor growth and tumor-associated angiogenesis in a PCa
      xenograft mouse model. Our results indicate that PCa-secreted CCN3 can recruit
      macrophages and skew their differentiation to an M2 phenotype. In turn, CCN3
      stimulated macrophages contribute to VEGF-dependent angiogenesis. This study
      reveals a novel mechanism by which TAMs enhance PCa angiogenesis and identifies a
      potential therapeutic target for PCa. 

PMID- 24721787
TI  - Superresolution imaging of human cytomegalovirus vMIA localization in sub
      mitochondrial compartments.
AB  - The human cytomegalovirus (HCMV) viral mitochondria-localized inhibitor of
      apoptosis (vMIA) protein, traffics to mitochondria-associated membranes (MAM),
      where the endoplasmic reticulum (ER) contacts the outer mitochondrial membrane
      (OMM). vMIA association with the MAM has not been visualized by imaging. Here, we
      have visualized this by using a combination of confocal and superresolution
      imaging. Deconvolution of confocal microscopy images shows vMIA localizes away
      from mitochondrial matrix at the Mitochondria-ER interface. By gated stimulated
      emission depletion (GSTED) imaging, we show that along this interface vMIA is
      distributed in clusters. Through multicolor, multifocal structured illumination
      microscopy (MSIM), we find vMIA clusters localize away from MitoTracker Red,
      indicating its OMM localization. GSTED and MSIM imaging show vMIA exists in
      clusters of ~100-150 nm, which is consistent with the cluster size determined by
      Photoactivated Localization Microscopy (PALM). With these diverse superresolution
      approaches, we have imaged the clustered distribution of vMIA at the OMM adjacent
      to the ER. Our findings directly compare the relative advantages of each of these
      superresolution imaging modalities for imaging components of the MAM and sub
      mitochondrial compartments. These studies establish the ability of
      superresolution imaging to provide valuable insight into viral protein location,
      particularly in the sub-mitochondrial compartments, and into their clustered
      organization. 

PMID- 24721788
TI  - Generation of West Nile virus infectious clones containing amino acid insertions
      between capsid and capsid anchor.
AB  - West Nile virus (WNV) is a positive-sense RNA arbovirus responsible for recent
      outbreaks of severe neurological disease within the US and Europe. Large-scale
      analyses of antiviral compounds that inhibit virus replication have been limited
      due to the lack of an adequate WN reporter virus. Previous attempts to insert a
      reporter into the 3' untranslated region of WNV generated unstable viruses,
      suggesting that this region does not accommodate additional nucleotides. Here, we
      engineered two WNV infectious clones containing insertions at the Capsid
      (C)/Capsid Anchor (CA) junction of the viral polyprotein. Recombinant viruses
      containing a TAT(1-67) or Gaussia Luciferase (GLuc) gene at this location were
      successfully recovered. However, rapid loss of most, if not all, of the reporter
      sequence occurred for both viruses, indicating that the reporter viruses were not
      stable. While the GLuc viruses predominantly reverted back to wild-type WNV
      length, the TAT viruses retained up to 75 additional nucleotides of the reporter
      sequence. These additional nucleotides were stable over at least five passages
      and did not significantly alter WNV fitness. Thus, the C/CA junction of WNV can
      tolerate additional nucleotides, though insertions are subject to certain
      constraints. 

PMID- 24721789
TI  - Analysis of determinants in filovirus glycoproteins required for tetherin
      antagonism.
AB  - The host cell protein tetherin can restrict the release of enveloped viruses from
      infected cells. The HIV-1 protein Vpu counteracts tetherin by removing it from
      the site of viral budding, the plasma membrane, and this process depends on
      specific interactions between the transmembrane domains of Vpu and tetherin. In
      contrast, the glycoproteins (GPs) of two filoviruses, Ebola and Marburg virus,
      antagonize tetherin without reducing surface expression, and the domains in GP
      required for tetherin counteraction are unknown. Here, we show that filovirus GPs
      depend on the presence of their authentic transmembrane domains for virus-cell
      fusion and tetherin antagonism. However, conserved residues within the
      transmembrane domain were dispensable for membrane fusion and tetherin
      counteraction. Moreover, the insertion of the transmembrane domain into a
      heterologous viral GP, Lassa virus GPC, was not sufficient to confer tetherin
      antagonism to the recipient. Finally, mutation of conserved residues within the
      fusion peptide of Ebola virus GP inhibited virus-cell fusion but did not ablate
      tetherin counteraction, indicating that the fusion peptide and the ability of GP
      to drive host cell entry are not required for tetherin counteraction. These
      results suggest that the transmembrane domains of filoviral GPs contribute to
      tetherin antagonism but are not the sole determinants. 

PMID- 24721790
TI  - Respiratory manganese particle size, time-course and neurobehavioral outcomes in
      workers at a manganese alloy production plant.
AB  - The progression of manganism with chronic exposure to airborne manganese (Mn) is
      not well understood. Here, we further investigate the findings on exposure and
      neurobehavioral outcomes of workers from a silico- and ferromanganese production
      plant and non-exposed workers from the same community in 1990 and 2004, using a
      variety of exposure metrics that distinguish particle size and origin within the
      range of respirable airborne exposures. Mn exposure matrices for large respirable
      particulate (Mn-LRP, dust) and small respirable particulate (Mn-SRP, fume), based
      on process origins, were used together with detailed work histories since 1973
      (plant opening), to construct exposure metrics including burdens and cumulative
      burdens with various clearance half-lives. For three out of eight 1990
      neurobehavioral tests analyzed with linear regression models, duration of Mn
      exposure was the best predictor: Luria-Nebraska Neuropsychological Battery -
      Motor Scale, Trail-Making B and Finger Tapping. The Luria-Nebraska Motor Scale
      had the strongest association (t ~ 5.0, p < 10(-6)). For outcomes on three other
      tests, the duration and Mn-SRP metrics were comparable: Trail Making Test A,
      Cancellation H and Stroop Color-Word Test (color/word subtest). Delayed Word
      Recall was best predicted by Mn-SRP (based on square root or truncated air
      concentrations). The Word score on the Stroop Color-Word Test was the only
      outcome for which Mn-LRP was the leading predictor (t = -2.92, p = 0.003), while
      performance on the WAIS-R Digit Span Test was not significantly predicted by any
      metric. For outcomes evaluated in both 1990 and 2004, a mixed-effect linear
      regression model was used to examine estimates of within-individual trends.
      Duration and Mn-SRP were associated with performance on the Luria-Nebraska Motor
      Scale, as well as with other outcomes that appeared to have both reversible and
      progressive features, including Trail Making A and B, Cancellation H and Delayed
      Word Recall. With the mixed-effect model, Digit Span exhibited a significant
      irreversible association with exposure duration (t = -2.34, p = 0.021) and Mn-SRP
      (square root; t = -2.38, p = 0.019) metrics. The strong prediction using duration
      of exposure is consistent with effective homeostatic regulation of tissue-level
      Mn in the observed exposure range of respirable Mn (< 0.2mg/m(3)).

PMID- 24721791
TI  - Synergistic antitumor activity of lenalidomide with the BET bromodomain inhibitor
      CPI203 in bortezomib-resistant mantle cell lymphoma.
AB  - Bortezomib therapy has shown promising clinical activity in mantle cell lymphoma
      (MCL), but the development of resistance to proteasome inhibition may limit its
      efficacy. To unravel the factors involved in the acquisition of bortezomib
      resistance in vivo, immunodeficient mice were engrafted with a set of MCL cell
      lines with different levels of sensitivity to the drug, followed by gene
      expression profiling of the tumors and functional validation of the identified
      gene signatures. We observed an increased tumorigenicity of bortezomib-resistant
      MCL cells in vivo, which was associated with plasmacytic differentiation
      features, like interferon regulatory factor 4 (IRF4) and Blimp-1 upregulation.
      Lenalidomide was particularly active in this subgroup of tumors, targeting IRF4
      expression and plasmacytic differentiation program, thus overcoming bortezomib
      resistance. Moreover, repression of the IRF4 target gene MYC in bortezomib
      resistant cells by gene knockdown or treatment with CPI203, a BET (bromodomain
      and extra terminal) bromodomain inhibitor, synergistically induced cell death
      when combined with lenalidomide. In mice, addition of CPI203 to lenalidomide
      therapy further decreased tumor burden, involving simultaneous MYC and IRF4
      downregulation and apoptosis induction. Together, these results suggest that
      exacerbated IRF4/MYC signaling is associated to bortezomib resistance in MCL in
      vivo and warrant clinical evaluation of lenalidomide plus BET inhibitor
      combination in MCL cases refractory to proteasome inhibition.

PMID- 24721793
TI  - Multisystem failure: the story of anti-influenza drugs.

PMID- 24721792
TI  - Heterogeneity of clonal expansion and maturation-linked mutation acquisition in
      hematopoietic progenitors in human acute myeloid leukemia.
AB  - Recent technological advances led to an appreciation of the genetic complexity of
      human acute myeloid leukemia (AML), but underlying progenitor cells remain poorly
      understood because their rarity precludes direct study. We developed a co-culture
      method integrating hypoxia, aryl hydrocarbon receptor inhibition and micro
      environmental support via human endothelial cells to isolate these cells. X
      chromosome inactivation studies of the least mature precursors derived following
      prolonged culture of CD34(+)/CD33(-) cells revealed polyclonal growth in highly
      curable AMLs, suggesting that mutations necessary for clonal expansion were
      acquired in more mature progenitors. Consistently, in core-binding factor (CBF)
      leukemias with known complementing mutations, immature precursors derived
      following prolonged culture of CD34(+)/CD33(-) cells harbored neither mutation or
      the CBF mutation alone, whereas more mature precursors often carried both
      mutations. These results were in contrast to those with leukemias with poor
      prognosis that showed clonal dominance in the least mature precursors. These data
      indicate heterogeneity among progenitors in human AML that may have prognostic
      and therapeutic implications.

PMID- 24721794
TI  - Mkk4 is a negative regulator of the transforming growth factor beta 1 signaling
      associated with atrial remodeling and arrhythmogenesis with age.
AB  - BACKGROUND: Atrial fibrillation (AF), often associated with structural, fibrotic
      change in cardiac tissues involving regulatory signaling mediators, becomes
      increasingly common with age. In the present study, we explored the role of
      mitogen-activated protein kinase kinase 4 (Mkk4), a critical component of the
      stress-activated mitogen-activated protein kinase family, in age-associated AF.
      METHODS AND RESULTS: We developed a novel mouse model with a selective
      inactivation of atrial cardiomyocyte Mkk4 (Mkk4(ACKO)). We characterized and
      compared electrophysiological, histological, and molecular features of young (3-
      to 4-month), adult (6-month), and old (1-year) Mkk4(ACKO) mice with age-matched
      control littermates (Mkk4(F/F)). Aging Mkk4(ACKO) mice were more susceptible to
      atrial tachyarrhythmias than the corresponding Mkk4(F/F) mice, showing
      characteristic slow and dispersed atrial conduction, for which modeling studies
      demonstrated potential arrhythmic effects. These differences paralleled increased
      interstitial fibrosis, upregulated transforming growth factor beta 1 (TGF-beta1)
      signaling and dysregulation of matrix metalloproteinases in Mkk4(ACKO), compared
      to Mkk4(F/F), atria. Mkk4 inactivation increased the sensitivity of cultured
      cardiomyocytes to angiotensin II-induced activation of TGF-beta1 signaling. This,
      in turn, enhanced expression of profibrotic molecules in cultured cardiac
      fibroblasts, suggesting cross-talk between these two cell types in profibrotic
      signaling. Finally, human atrial tissues in AF showed a Mkk4 downregulation
      associated with increased production of profibrotic molecules, compared to
      findings in tissue from control subjects in sinus rhythm. CONCLUSIONS: These
      findings together demonstrate, for the first time, that Mkk4 is a negative
      regulator of the TGF-beta1 signaling associated with atrial remodeling and
      arrhythmogenesis with age, establishing Mkk4 as a new potential therapeutic
      target for treating AF.

PMID- 24721795
TI  - Compliance with acute stroke care quality measures in hospitals with and without
      primary stroke center certification: the North Carolina Stroke Care
      Collaborative.
AB  - BACKGROUND: Organized stroke care is associated with improved outcomes. Data are
      limited on differences in changes in the quality of acute stroke care at The
      Joint Commission-certified Primary Stroke Centers (PSCs) versus non-PSCs over
      time. METHODS AND RESULTS: We compared compliance with the Joint Commission's 10
      acute stroke care performance measures and defect-free care in PSCs and non-PSCs
      participating in the Registry of the North Carolina Stroke Care Collaborative
      from January 2005 through February 2010. We included 29 654 cases presenting at
      47 hospitals-10 PSCs, 8 preparing for certification, and 29 non-PSCs-representing
      43% of North Carolina's non-Veterans Affairs, acute care hospitals. Using a non
      PSC referent, odds ratios and 95% CIs were calculated using logistic regression
      and generalized estimating equations accounting for clustering of cases within
      hospitals. Time trends were presented graphically using simple linear regression.
      Performance measure compliance increased for all measures for all 3 groups in
      2005-2010, with the exception of discharge on antithrombotics, which remained
      consistently high. PSCs and hospitals preparing for certification had better
      compliance with all but 2 performance measures compared with non-PSCs (each
      P<0.01). Defect-free care was delivered most consistently at hospitals preparing
      for certification (52.8%), followed by PSCs (45.0%) and non-PSCs (21.9%). Between
      2005 and 2010, PSCs and hospitals preparing for certification had a higher
      average annual percent increase in the provision of defect-free care (P=0.01 and
      0.04, respectively) compared with non-PSCs. CONCLUSIONS: PSC certification is
      associated with an overall improvement in the quality of stroke care in North
      Carolina; however, room for improvement remains.

PMID- 24721796
TI  - Exercise, vascular stiffness, and tissue transglutaminase.
AB  - BACKGROUND: Vascular aging is closely associated with increased vascular
      stiffness. It has recently been demonstrated that decreased nitric oxide (NO)
      induced S-nitrosylation of tissue transglutaminase (TG2) contributes to age
      related vascular stiffness. In the current study, we tested the hypothesis that
      exercise restores NO signaling and attenuates vascular stiffness by decreasing
      TG2 activity and cross-linking in an aging rat model. METHODS AND RESULTS: Rats
      were subjected to 12 weeks of moderate aerobic exercise. Aging was associated
      with diminished phosphorylated endothelial nitric oxide synthase and
      phosphorylated vasodilator-stimulated phosphoprotein abundance, suggesting
      reduced NO signaling. TG2 cross-linking activity was significantly increased in
      old animals, whereas TG2 abundance remained unchanged. These alterations were
      attenuated in the exercise cohort. Simultaneous measurement of blood pressure and
      pulse wave velocity (PWV) demonstrated increased aortic stiffness in old rats,
      compared to young, at all values of mean arterial pressure (MAP). The PWV-MAP
      correlation in the old sedentary and old exercise cohorts was similar. Tensile
      testing of the vessels showed increased stiffness of the aorta in the old
      phenotype with a modest restoration of mechanical properties toward the young
      phenotype with exercise. CONCLUSIONS: Increased vascular stiffness during aging
      is associated with decreased TG2 S-nitrosylation, increased TG2 cross-linking
      activity, and increased vascular stiffness likely the result of decreased NO
      bioavailability. In this study, a brief period of moderate aerobic exercise
      enhanced NO signaling, attenuated TG cross-linking activity, and reduced ex vivo
      tensile properties, but failed to reverse functional vascular stiffness in vivo,
      as measured by PWV.

PMID- 24721798
TI  - Associations between body mass index and development of metabolic disorders in
      fertile women--a nationwide cohort study.
AB  - BACKGROUND: Metabolic disorders are relatively uncommon in young women, but may
      increase with obesity. The associations between body mass index (BMI) and risks
      of diabetes, hypertension, and dyslipidemia in apparently healthy, young women
      have been insufficiently investigated, and are the aims of this study. METHODS
      AND RESULTS: Women giving birth during the years 2004-2009, with no history of
      cardiovascular disease, renal insufficiency, pregnancy-associated metabolic
      disorders, diabetes, hypertension, or dyslipidemia were identified in nationwide
      registers. Women were categorized as underweight (BMI<18.5 kg/m(2)), normal
      weight (BMI=18.5 to <25 kg/m(2)), overweight (BMI=25 to <30 kg/m(2)), obese-I
      (BMI=30 to <35 kg/m(2)), obese-II (BMI=35 to <40 kg/m(2)), and obese-III (BMI>=40
      kg/m(2)). We assessed risks by Poisson regression models (adjusted for age,
      calendar year; reference=normal weight). The cohort comprised 252 472 women with
      a median age of 30.4 years (IQR=27.2;33.7) and a median follow-up of 5.5 years
      (IQR=3.9;6.8). In total, 2029 women developed diabetes, 3133 women developed
      hypertension, and 1549 women developed dyslipidemia. Rate ratios (RRs) of
      diabetes were: 0.84 (95% confidence interval [CI]=0.62 to 1.14) for underweight,
      2.63 (CI=2.36 to 2.93) for overweight, 4.83 (CI=4.27 to 5.47) for obese grade-I,
      7.17 (CI=6.10 to 8.48) for obese grade-II, and 6.93 (CI=5.47 to 8.79) for obese
      grade-III women. For hypertension, corresponding RRs were 0.86 (CI=0.69 to 1.09),
      1.82 (CI=1.67 to 1.98), 2.81 (CI=2.52 to 3.13), 3.92 (CI=3.36 to 4.56), and 5.69
      (CI=4.71 to 6.89), and for dyslipidemia, RRs were 1.18 (CI=0.85 to 1.65), 2.01
      (CI=1.75 to 2.31), 3.11 (CI=2.61 to 3.70), 4.64 (CI=3.66 to 5.87), and 3.72
      (CI=2.53 to 5.48). CONCLUSIONS: In this nationwide study of fertile, apparently
      healthy women, pre-pregnancy BMI was strongly associated with an increased risk
      of diabetes, hypertension, and dyslipidemia within 5.5 years following
      childbirth.

PMID- 24721797
TI  - The TLR9 ligand, CpG-ODN, induces protection against cerebral
      ischemia/reperfusion injury via activation of PI3K/Akt signaling.
AB  - BACKGROUND: Toll-like receptors (TLRs) have been shown to be involved in cerebral
      ischemia/reperfusion (I/R) injury. TLR9 is located in intracellular compartments
      and recognizes CpG-DNA. This study examined the effect of CpG-ODN on cerebral I/R
      injury. METHODS AND RESULTS: C57BL/6 mice were treated with CpG-ODN by i.p.
      injection 1 hour before the mice were subjected to cerebral ischemia (60 minutes)
      followed by reperfusion (24 hours). Scrambled-ODN served as control-ODN.
      Untreated mice, subjected to cerebral I/R, served as I/R control. The effect of
      inhibitory CpG-ODN (iCpG-ODN) on cerebral I/R injury was also examined. In
      addition, we examined the therapeutic effect of CpG-ODN on cerebral I/R injury by
      administration of CpG-ODN 15 minutes after cerebral ischemia. CpG-ODN
      administration significantly decreased cerebral I/R-induced infarct volume by
      69.7% (6.4+/-1.80% vs 21.0+/-2.85%, P<0.05), improved neurological scores, and
      increased survival rate, when compared with the untreated I/R group. Therapeutic
      administration of CpG-ODN also significantly reduced infarct volume by 44.7%
      (12.6+/-2.03% vs 22.8+/-2.54%, P<0.05) compared with untreated I/R mice. Neither
      control-ODN, nor iCpG-ODN altered I/R-induced cerebral injury or neurological
      deficits. Nissl staining showed that CpG-ODN treatment preserved neuronal
      morphology in the ischemic hippocampus. Immunoblot showed that CpG-ODN
      administration increased Bcl-2 levels by 41% and attenuated I/R-increased levels
      of Bax and caspase-3 activity in ischemic brain tissues. Importantly, CpG-ODN
      treatment induced Akt and GSK-3beta phosphorylation in brain tissue and cultured
      microglial cells. PI3K inhibition with LY294002 abolished CpG-ODN-induced
      protection. CONCLUSION: CpG-ODN significantly reduces cerebral I/R injury via a
      PI3K/Akt-dependent mechanism. Our data also indicate that CpG-ODN may be useful
      in the therapy of cerebral I/R injury.

PMID- 24721799
TI  - Adherence to guideline-recommended therapy is associated with decreased major
      adverse cardiovascular events and major adverse limb events among patients with
      peripheral arterial disease.
AB  - BACKGROUND: Current guidelines recommend that patients with peripheral arterial
      disease (PAD) cease smoking and be treated with aspirin, statin medications, and
      angiotensin-converting enzyme (ACE) inhibitors. The combined effects of multiple
      guideline-recommended therapies in patients with symptomatic PAD have not been
      well characterized. METHODS AND RESULTS: We analyzed a comprehensive database of
      all patients with claudication or critical limb ischemia (CLI) who underwent
      diagnostic or interventional lower-extremity angiography between June 1, 2006 and
      May 1, 2013 at a multidisciplinary vascular center. Baseline demographics,
      clinical data, and long-term outcomes were obtained. Inverse probability of
      treatment propensity weighting was used to determine the 3-year risk of major
      adverse cardiovascular or cerebrovascular events (MACE; myocardial infarction,
      stroke, or death) and major adverse limb events (MALE; major amputation,
      thrombolysis, or surgical bypass). Among 739 patients with PAD, 325 (44%) had
      claudication and 414 (56%) had CLI. Guideline-recommended therapies at baseline
      included use of aspirin in 651 (88%), statin medications in 496 (67%), ACE
      inhibitors in 445 (60%), and smoking abstention in 528 (71%) patients. A total of
      237 (32%) patients met all four guideline-recommended therapies. After adjustment
      for baseline covariates, patients adhering to all four guideline-recommended
      therapies had decreased MACE (hazard ratio [HR], 0.64; 95% CI, 0.45 to 0.89;
      P=0.009), MALE (HR, 0.55; 95% CI, 0.37 to 0.83; P=0.005), and mortality (HR,
      0.56; 95% CI, 0.38 to 0.82; P=0.003), compared to patients receiving less than
      four of the recommended therapies. CONCLUSIONS: In patients with claudication or
      CLI, combination treatment with four guideline-recommended therapies is
      associated with significant reductions in MACE, MALE, and mortality.

PMID- 24721800
TI  - Postural tachycardia syndrome and inappropriate sinus tachycardia: role of
      autonomic modulation and sinus node automaticity.
AB  - BACKGROUND: Inappropriate sinus tachycardia (IST) and postural tachycardia
      syndrome (POTS) are 2 disorders characterized by sinus tachycardia. It is debated
      whether the pathophysiology of IST and POTS results from abnormal autonomic
      regulation or abnormal sinus node function. We hypothesized that intrinsic heart
      rate (IHR) after autonomic blockade would be increased in patients with IST but
      not POTS. METHODS AND RESULTS: We enrolled 48 POTS patients, 8 IST patients, and
      17 healthy control (HC) subjects. Intravenous propranolol and atropine were given
      to block the sympathetic and parasympathetic limbs of the autonomic nervous
      system in order to determine the IHR. Patients with IST have a higher sympathetic
      contribution to heart rate when compared with POTS patients (31+/-13 bpm versus
      12+/-7 bpm, P<0.001) and HC (8+/-4 bpm; P<0.001) and a trend to less
      parasympathetic contribution than POTS and HC (IST: 31+/-11 bpm versus POTS: 46+/
      11 bpm versus HC: 48+/-11 bpm, ANOVA P=0.108). IHR was not significantly
      different between IST and either POTS or HC (IST: 111+/-11 bpm versus POTS: 108+/
      11 bpm versus HC: 106+/-12 bpm, ANOVA P=0.237). CONCLUSIONS: IST patients have
      more sympathetic tone when compared with either POTS or HC, but IST patients do
      not have abnormal sinus node automaticity. These data suggest that the treatment
      of IST and POTS should focus on sympatholysis, reserving sinus node modification
      for patients with continued debilitating symptoms after beta-blockade and
      possibly ivabradine. CLINICAL TRIAL REGISTRATION URL: http://clinicaltrials.gov/.
      Unique identifier: NCT00262470.

PMID- 24721802
TI  - iPad2(R) use in patients with implantable cardioverter defibrillators causes
      electromagnetic interference: the EMIT Study.
AB  - BACKGROUND: Over 140 million iPads((r)) have been sold worldwide. The iPad2((r)),
      with magnets embedded in its frame and Smart Cover and 3G cellular data
      capability, can potentially cause electromagnetic interference in implantable
      cardioverter defibrillators. This can lead to potentially life-threatening
      situations in patients. The goal of this study was to determine whether the
      iPad2((r)) can cause electromagnetic interference in patients with implantable
      cardioverter defibrillators. METHODS AND RESULTS: Twenty-seven patients with
      implantable cardioverter defibrillators were studied. The iPad2((r)) was held at
      reading distance and placed directly over the device with cellular data
      capability activated and deactivated. The manufacturers/models of devices and the
      patients' body mass index were noted. The presence of electromagnetic
      interference was detected by using a programmer supplied by each manufacturer.
      Magnet mode with suspension of anti-tachycardia therapy was triggered in 9 (33%)
      patients. All occurred when the iPad2((r)) was placed directly over the device.
      The cellular data status did not cause interference and no noise or oversensing
      was noted. There was no significant difference between the mean body mass index
      of the groups with or without interference. CONCLUSIONS: The iPad2((r)) can
      trigger magnet mode in implantable cardioverter defibrillators when laid directly
      over the device. This is potentially dangerous if patients should develop life
      threatening arrhythmias at the same time. As new electronic products that use
      magnets are produced, the potential risk to patients with implantable
      defibrillators needs to be addressed.

PMID- 24721801
TI  - Improving blood pressure control through pharmacist interventions: a meta
      analysis of randomized controlled trials.
AB  - BACKGROUND: Control of blood pressure (BP) remains a major challenge in primary
      care. Innovative interventions to improve BP control are therefore needed. By
      updating and combining data from 2 previous systematic reviews, we assess the
      effect of pharmacist interventions on BP and identify potential determinants of
      heterogeneity. METHODS AND RESULTS: Randomized controlled trials (RCTs) assessing
      the effect of pharmacist interventions on BP among outpatients with or without
      diabetes were identified from MEDLINE, EMBASE, CINAHL, and CENTRAL databases.
      Weighted mean differences in BP were estimated using random effect models.
      Prediction intervals (PI) were computed to better express uncertainties in the
      effect estimates. Thirty-nine RCTs were included with 14 224 patients. Pharmacist
      interventions mainly included patient education, feedback to physician, and
      medication management. Compared with usual care, pharmacist interventions showed
      greater reduction in systolic BP (-7.6 mm Hg, 95% CI: -9.0 to -6.3; I(2)=67%) and
      diastolic BP (-3.9 mm Hg, 95% CI: -5.1 to -2.8; I(2)=83%). The 95% PI ranged from
      -13.9 to -1.4 mm Hg for systolic BP and from -9.9 to +2.0 mm Hg for diastolic BP.
      The effect tended to be larger if the intervention was led by the pharmacist and
      was done at least monthly. CONCLUSIONS: Pharmacist interventions - alone or in
      collaboration with other healthcare professionals - improved BP management.
      Nevertheless, pharmacist interventions had differential effects on BP, from very
      large to modest or no effect; and determinants of heterogeneity could not be
      identified. Determining the most efficient, cost-effective, and least time
      consuming intervention should be addressed with further research.

PMID- 24721803
TI  - Deamidated lipocalin-2 induces endothelial dysfunction and hypertension in
      dietary obese mice.
AB  - BACKGROUND: Lipocalin-2 is a proinflammatory adipokine upregulated in obese
      humans and animals. A pathogenic role of lipocalin-2 in hypertension has been
      suggested. Mice lacking lipocalin-2 are protected from dietary obesity-induced
      cardiovascular dysfunctions. Administration of lipocalin-2 causes abnormal
      vasodilator responses in mice on a high-fat diet (HFD). METHODS AND RESULTS: Wild
      type and lipocalin-2 knockout mice were fed with standard chow or HFD.
      Immunoassays were performed for evaluating the circulating and tissue contents of
      lipocalin-2. The relaxation and contraction of arteries were studied using a wire
      myograph. Blood pressure was monitored with implantable radio telemetry. Dietary
      obesity promoted the accumulation of lipocalin-2 protein in blood and arteries.
      Deficiency of this adipokine protected mice from dietary obesity-induced
      elevation of blood pressure. Mass spectrometry analysis revealed that human and
      murine lipocalin-2 were modified by polyamination. Polyaminated lipocalin-2 was
      rapidly cleared from the circulation. Adipose tissue was a major site for
      lipocalin-2 deamidation. The circulating levels and the arterial accumulation of
      deamidated lipocalin-2 were significantly enhanced by treatment with linoleic
      acid (18:2n-6), which bound to lipocalin-2 with high affinity and prevented its
      interactions with matrix metalloproteinase 9 (MMP9). Combined administration of
      linoleic acid with lipocalin-2 caused vascular inflammation and endothelial
      dysfunction and raised the blood pressure of mice receiving standard chow. A
      human lipocalin-2 mutant with cysteine 87 replaced by alanine (C87A) contained
      less polyamines and exhibited a reduced capacity to form heterodimeric complexes
      with MMP9. After treatment, C87A remained in the circulation for a prolonged
      period of time and evoked endothelial dysfunction in the absence of linoleic
      acid. CONCLUSIONS: Polyamination facilitates the clearance of lipocalin-2,
      whereas the accumulation of deamidated lipocalin-2 in arteries causes vascular
      inflammation, endothelial dysfunction, and hypertension.

PMID- 24721804
TI  - The interplay of transcription factors in suppression of UV-B induced flavonol
      accumulation by flg22.
AB  - Biotic stress can be mimicked by application of elicitors, which comprise of
      microbe-associated molecular patterns (MAMPs). Treatment of plant cell cultures
      with MAMPs such as flg22 suppressed the expression of UV-B-induced flavonol
      pathway genes (FPGs) in parsley, carrot and Arabidopsis. This is thought to allow
      the plant focusing its secondary metabolism on the pathogen defense during MAMP
      triggered immunity (MTI). Recently we reported that this suppression also depends
      on prevention of histone 3 acetylation at lysine 9 (H3K9ac), a hallmark for gene
      activation. Here we describe a possible regulation between UV-B and flg22
      signaling cascades, and the interplay of MYB and WRKY transcription factors in
      regulating the expression of the FPGs.

PMID- 24721806
TI  - Electric-field-modulated exchange coupling within and between magnetic clusters
      on metal surfaces: Mn dimers on Cu(1 1 1).
AB  - The effects of external electric fields (EFs) on the magnetic state and substrate
      mediated magnetic coupling between Mn dimers on Cu(1 1 1) have been studied using
      a first-principles theoretical method. The calculations show that a change in the
      ground-state magnetic order, from antiferromagnetic (AF) to ferromagnetic (FM),
      can be induced within an isolated Mn2 on Cu(1 1 1) by applying a moderately
      strong EF of about 1 V A(-1). The magnetic exchange coupling between pairs of
      dimers displays Ruderman-Kittel-Kasuya-Yosida-like oscillations as a function of
      the interdimer distance, which depend significantly on the magnetic order within
      the dimers (FM or AF) and on their relative orientation on the surface. Moreover,
      it is observed that applying EFs allows modulation of the exchange coupling
      within and between the clusters as a function of the intercluster distance. At
      short distances, AF order within the dimers is favoured even in the presence of
      EFs, while for large distances the EF can induce a FM order. EFs pointing
      outwards and inwards with respect to the surface favour parallel and antiparallel
      magnetic alignment between the dimers, resspectively. The dependence of the
      substrate-mediated interaction on the magnetic state of Mn2 is qualitatively
      interpreted in terms of the differences in the scattering of spin-polarized
      surface electrons.

PMID- 24721805
TI  - Photoluminescent carbon nanotags from harmful cyanobacteria for drug delivery and
      imaging in cancer cells.
AB  - Using a simple method of mass production of green carbon nanotags (G-tags) from
      harmful cyanobacteria, we developed an advanced and efficient imaging platform
      for the purpose of anticancer therapy. Approximately 100 grams of G-tags per 100
      kilograms of harmful cyanobacteria were prepared using our eco-friendly approach.
      The G-tags possess high solubility, excellent photostability, and low
      cytotoxicity (<1.5 mg/mL for 24 h). Moreover, doxorubicin-conjugated G-tags (T
      tags; >0.1 mg/mL) induced death in cancer cells (HepG2 and MCF-7) in-vitro at a
      higher rate than that of only G-tags while in-vivo mice experiment showed
      enhanced anticancer efficacy by T-tags at 0.01 mg/mL, indicating that the loaded
      doxorubicin retains its pharmaceutical activity. The cancer cell uptake and
      intracellular location of the G- and T-tags were observed. The results indicate
      that these multifunctional T-tags can deliver doxorubicin to the targeted cancer
      cells and sense the delivery of doxorubicin by activating the fluorescence of G
      tags.

PMID- 24721807
TI  - Oral anticoagulant therapy and clinical outcomes in patients with atrial
      fibrillation: a pilot study from a single center registry.
AB  - The data on the successful use of oral anticoagulation (OAC) in patients with
      atrial fibrillation are inconclusive. We aimed to describe the indications and
      the utilization patterns of OAC therapy in patients with atrial fibrillation who
      have been admitted to a quaternary hospital. Patients who were admitted to a
      quaternary hospital from January 2011 to January 2012 with atrial fibrillation
      were included in the study. The data on patient demographics, atrial fibrillation
      classification, CHA2DS2VASc scores, and the use of OAC were collected. Of the
      patients admitted, 301 patients met the inclusion criteria. Of these, 277 (92%)
      had a CHA2DS2VASc score at least 2. Of the patients who met criteria for
      treatment with OAC, 104 (36.6%) were not on OAC therapy. The reason for this
      discrepancy was tendency and history of bleeding (29.8%). Of those 180 patients
      who were on OAC, the time in therapeutic range was higher in those patients less
      than 50 years as compared with those between ages 65-74 and more than 75 (78.2
      versus 42 and 36.1%, P < 0.05). The overall time in therapeutic range of patients
      on OAC was 47.4%. We found that approximately one-third of the patients who have
      indications for OAC are not being treated as per guidelines due to history of and
      tendency for bleeding. Furthermore, of those on OAC, only half of the patients
      achieved successful anticoagulation. 

PMID- 24721808
TI  - Diffusion tensor imaging alterations in patients with postconcussion syndrome
      undergoing exercise treatment: a pilot longitudinal study.
AB  - PURPOSE: To investigate diffusion tensor imaging characteristics in patients with
      postconcussion syndrome (PCS) who received exercise (n = 4) and placebo
      stretching (n = 4) treatments compared with a group of healthy controls (n = 15).
      METHODS: Subjects diagnosed with PCS obtained a diffusion tensor imaging magnetic
      resonance image at pretreatment (baseline) and approximately 8 weeks later
      (follow-up). Analyses included a groupwise comparison using tract-based spatial
      statistics and a z-score map that investigated localized regional anomalies
      compared with the healthy control group projected onto the tract-based spatial
      statistics skeleton. RESULTS: The tract-based spatial statistics analysis
      detected groupwise differences in the genu of the corpus callosum at both time
      points with decreased fractional anisotropy and increased radial diffusivity and
      mean diffusivity values. In contrast, the z-score analysis was more sensitive to
      heterogeneous changes in fractional anisotropy, with both low- and high-localized
      areas across various white matter regions, the most prevalent being the corpus
      callosum, anterior and superior corona radiata, and internal and external
      capsules. The mean number of voxels different in patients with PCS versus healthy
      controls was greater in all cases (baseline lower: P < .03 and higher: P < .0001;
      follow-up lower: P < .0001 and higher: P < .0001). The volume and location of
      these abnormal regions changed between the 2 diffusion tensor imaging scans, but
      these did not correlate with the mitigation of symptoms in the patients with PCS.
      CONCLUSIONS: Diffusion tensor imaging revealed spatially varying and
      heterogeneous localized irregularities in patients with PCS that persisted even
      as patient symptoms decreased and prognosis improved.

PMID- 24721809
TI  - Factors influencing self-awareness following traumatic brain injury.
AB  - OBJECTIVE: To examine self-awareness and injury-related, emotional and
      demographic factors across acute/subacute (3-12 months), medium-term (24-60
      months), and long-term (120-240 months) time periods after traumatic brain injury
      (TBI), because unawareness of injury-related changes can affect engagement in
      rehabilitation and functional outcomes. PARTICIPANTS: A total of 168 individuals
      with mild to severe TBI and 105 of their close others. MAIN OUTCOMES MEASURES:
      Awareness Questionnaire (AQ) and Hospital Anxiety and Depression Scale. DESIGN:
      Cross-sectional study. RESULTS: There were no significant differences in
      awareness as a function of time postinjury, except for the AQ motor/sensory
      domain wherein individuals with TBI at longer time periods displayed increased
      awareness of deficits than those at earlier time periods. Greater patient-other
      AQ discrepancy scores (interpreted as lower patient awareness) were associated
      with longer posttraumatic amnesia duration in the individual with TBI and also
      with increased self-reported depressive symptoms in the close others. Conversely,
      smaller AQ discrepancy scores (interpreted as better awareness) were associated
      with increased self-reported depressive symptoms by the individuals with TBI.
      CONCLUSION: This study highlights the limitations of using discrepancy scores to
      measure awareness, as ratings of injury-related changes are influenced by the
      mood of the individual with TBI and the close other, as well as by injury
      severity.

PMID- 24721810
TI  - The reliability, validity, and feasibility of physical activity measurement in
      adults with traumatic brain injury: an observational study.
AB  - OBJECTIVE: To determine the reliability and validity of the Physical Activity
      Scale for Individuals with a Physical Disability (PASIPD) in adults with severe
      traumatic brain injury (TBI) and estimate the proportion of the sample
      participants who fail to meet the World Health Organization guidelines for
      physical activity. DESIGN AND PARTICIPANTS: A single-center observational study
      recruited a convenience sample of 30 community-based ambulant adults with severe
      TBI. PROTOCOL: Participants completed the PASIPD on 2 occasions, 1 week apart,
      and wore an accelerometer (ActiGraph GT3X; ActiGraph LLC, Pensacola, Florida) for
      the 7 days between these 2 assessments. RESULTS: The PASIPD test-retest
      reliability was substantial (intraclass correlation coefficient = 0.85; 95%
      confidence interval, 0.70-0.92), and the correlation with the accelerometer
      ranged from too low to be meaningful (R = 0.09) to moderate (R = 0.57). From
      device-based measurement of physical activity, 56% of participants failed to meet
      the World Health Organization physical activity guidelines. CONCLUSION: The
      PASIPD is a reliable measure of the type of physical activity people with severe
      TBI participate in, but it is not a valid measure of the amount of moderate to
      vigorous physical activity in which they engage. Accelerometers should be used to
      quantify moderate to vigorous physical activity in people with TBI.

PMID- 24721811
TI  - A Model of Fatigue Following Traumatic Brain Injury.
AB  - OBJECTIVE: Fatigue is one of the most frequent sequelae of traumatic brain injury
      (TBI), although its causes are poorly understood. This study investigated the
      interrelationships between fatigue and sleepiness, vigilance performance,
      depression, and anxiety, using a structural equation modeling approach. METHODS:
      Seventy-two participants with moderate to severe TBI (78% males) were recruited a
      median of 305 days postinjury. They completed the Fatigue Severity Scale, a
      vigilance task, the Epworth Sleepiness Scale, and Hospital Anxiety and Depression
      Scale. A model of the interrelationships between the study variables was
      developed, tested, and modified with path analysis. RESULTS: The modified model
      had a good overall fit (chi2 = 1.3, P = .54; comparative fit index = 1.0; root
      mean square error of approximation = 0.0; standardized root-mean square residual
      = 0.02). Most paths in this model were significant (P < .05). Fatigue predicted
      anxiety, depression, and daytime sleepiness. Depression predicted daytime
      sleepiness and poor vigilance, whereas anxiety tended to predict reduced daytime
      sleepiness. CONCLUSIONS: This model confirms the complexity of fatigue
      experience. It supports the hypothesis that fatigue after TBI is a cause, not a
      consequence, of anxiety, depression, and daytime sleepiness, which, in turn
      (especially depression), may exacerbate fatigue by affecting cognitive
      functioning. These findings suggest that to alleviate fatigue, it is important to
      address each of these factors. However, the findings need to be confirmed with a
      longitudinal research design.

PMID- 24721812
TI  - Endoscopic versus microscopic transsphenoidal pituitary adenoma surgery: a meta
      analysis.
AB  - BACKGROUND: Endoscopic transsphenoidal surgery has gradually come to be regarded
      as a preferred option in the treatment of pituitary adenomas because of its
      advantages of improved visualization and its minimal invasiveness. The aim of
      this study was to compare and evaluate the outcomes and complications of
      endoscopic and microscopic transsphenoidal surgery in the treatment of pituitary
      adenomas. METHODS: We performed a systematic literature search of MEDLINE,
      EMBASE, the Cochrane Library and the Web of Science between January 1992 and May
      2013. Studies with consecutive patients that explicitly and fully compared
      endoscopic and microscopic approaches in the treatment of pituitary adenomas were
      included. RESULTS: A total of 15 studies (n = 1,014 patients) met the inclusion
      criteria among 487 studies that involved endoscopic surgery and 527 studies that
      dealt with microscopic surgery. The rate of gross tumor removal was higher in the
      endoscopic group than in the microscopic group. The post-operative rates of
      septal perforation were less frequent in patients who underwent endoscopic
      surgery. There was no significant difference between the two techniques in the
      incidence rates of meningitis, diabetes insipidus, cerebrospinal fluid leak,
      epistaxis or hypopituitarism. The post-operative hospital stay was significantly
      shorter for the endoscopic surgery group compared with the microscopic surgery
      group (P < 0.05). There was no significant difference in the length of the
      operation (P > 0.05). CONCLUSIONS: The present study indicates that the
      endoscopic transsphenoidal approach is safer and more effective than microscopic
      surgery in the treatment of pituitary adenomas.

PMID- 24721813
TI  - Dual tobacco user subtypes in the U.S. Air Force: dependence, attitudes, and
      other correlates of use.
AB  - INTRODUCTION: To describe the characteristics associated with patterns of daily
      and dual tobacco use among U.S. Air Force (USAF) personnel transitioning from
      basic military training to technical training. METHODS: Cross-sectional survey of
      USAF personnel in Technical Training School at Lackland Air Force Base (N =
      8,956, response rate: 73%). Logistic regression analyzed the association of
      predictor variables between daily smokers, daily smokeless tobacco (ST) users,
      daily smokers who used ST nondaily, daily ST users who smoked cigarettes
      nondaily, and daily users of both cigarettes and ST. RESULTS: Compared to daily
      smokers, participants who were daily smokers/nondaily ST users were more likely
      to be male, would use ST and multiple forms of tobacco in the future, reported
      more friends using ST and cigarettes, and were more susceptible to tobacco
      advertising. Compared to daily ST users, daily ST users/nondaily cigarette users
      were more likely to live in the Midwest, would use multiple forms of tobacco in
      the future, reported more friends smoked cigarettes and used ST, and were more
      likely to try a product that claimed to be safer than cigarettes. Daily users of
      both cigarettes and ST were significantly more likely to be nicotine dependent
      than daily smokers/nondaily ST users and daily ST users/nondaily smokers.
      CONCLUSIONS: Dual users are heterogeneous groups of tobacco users who are at high
      risk for continued tobacco use. Daily users of both cigarettes and ST have higher
      levels of nicotine dependence, even when compared to other dual users. Specific
      interventions targeted at dual users are needed in this increasingly prevalent
      and high-risk population.

PMID- 24721814
TI  - Guilt and the burden on oncology providers.

PMID- 24721815
TI  - The seventh door.

PMID- 24721816
TI  - The letter to which I couldn't reply.

PMID- 24721817
TI  - Bevacizumab in treatment of high-risk ovarian cancer--a cost-effectiveness
      analysis.
AB  - The objective of this study was to evaluate a cost-effectiveness strategy of
      bevacizumab in a subset of high-risk advanced ovarian cancer patients with
      survival benefit. Methods. A subset analysis of the International Collaboration
      on Ovarian Neoplasms 7 trial showed that additions of bevacizumab (B) and
      maintenance bevacizumab (mB) to paclitaxel (P) and carboplatin (C) improved the
      overall survival (OS) of high-risk advanced cancer patients. Actual and estimated
      costs of treatment were determined from Medicare payment. Incremental cost
      effectiveness ratio per life-year saved was established. Results. The estimated
      cost of PC is $535 per cycle; PCB + mB (7.5 mg/kg) is $3,760 per cycle for the
      first 6 cycles and then $3,225 per cycle for 12 mB cycles. Of 465 high-risk stage
      IIIC (>1 cm residual) or stage IV patients, the previously reported OS after PC
      was 28.8 months versus 36.6 months in those who underwent PCB + mB. With an
      estimated 8-month improvement in OS, the incremental cost-effectiveness ratio of
      B was $167,771 per life-year saved. Conclusion. In this clinically relevant
      subset of women with high-risk advanced ovarian cancer with overall survival
      benefit after bevacizumab, our economic model suggests that the incremental cost
      of bevacizumab was approximately $170,000. 

PMID- 24721818
TI  - Caring for one of our own.
AB  - Schwartz Center Rounds are monthly multidisciplinary meetings where caregivers
      reflect on important psychosocial issues that they, along with patients and their
      families, face and gain insight and support from fellow staff members, with the
      goal of advancing compassionate health care, supporting caregivers, and fostering
      the connection between a clinician and his or her patients. This Schwartz Round
      focused on boundaries and the particular privileges and pressures of caring for a
      member of the staff. The article explores the tension between professional
      courtesy and empathic engagement. Major transitions can include the intrinsic
      fear of abandonment. Being "connected" is an important aspect of the patient
      caregiver relationship. Patient-centered care requires that we balance clinical
      acumen and medical technology with humanism throughout the different phases of a
      patient's experience with a life-threatening illness. 

PMID- 24721819
TI  - Ultra Q-bodies: quench-based antibody probes that utilize dye-dye interactions
      with enhanced antigen-dependent fluorescence.
AB  - Recently, we described a novel reagentless fluorescent biosensor strategy named
      Quenchbody, which functions via the antigen-dependent removal of the quenching
      effect on a fluorophore that is attached to a single-chain antibody variable
      region. To explore the practical utility of Quenchbodies, we prepared antibody
      Fab fragments that were fluorolabeled at either one or two of the N-terminal
      regions, using a cell-free translation-mediated position-specific protein
      labeling system. Unexpectedly, the Fab fragment labeled at the heavy chain N
      terminal region demonstrated a deeper quenching and antigen-dependent release
      compared to that observed using scFv. Moreover, when the Fab was fluorolabeled at
      the two N-termini with either the same dye or with two different dyes, an
      improved response due to enhanced quenching via dye-dye interactions was
      observed. On the basis of this approach, several targets, including peptides,
      proteins, and haptens, as well as narcotics, were quantified with a higher
      response up to 50-fold. In addition, differentiation of osteosarcoma to
      osteoblasts was successfully imaged using a similarly fluorolabeled recombinant
      Fab protein prepared from E. coli. Due to its versatility, this "Ultra
      Quenchbody" is expected to exhibit a range of applications from in vitro
      diagnostics to the live imaging of various targets in situ. 

PMID- 24721820
TI  - Bilingualism protects anterior temporal lobe integrity in aging.
AB  - Cerebral gray-matter volume (GMV) decreases in normal aging but the extent of the
      decrease may be experience-dependent. Bilingualism may be one protective factor
      and in this article we examine its potential protective effect on GMV in a region
      that shows strong age-related decreases-the left anterior temporal pole. This
      region is held to function as a conceptual hub and might be expected to be a
      target of plastic changes in bilingual speakers because of the requirement for
      these speakers to store and differentiate lexical concepts in 2 languages to
      guide speech production and comprehension processes. In a whole brain comparison
      of bilingual speakers (n = 23) and monolingual speakers (n = 23), regressing out
      confounding factors, we find more extensive age-related decreases in GMV in the
      monolingual brain and significantly increased GMV in left temporal pole for
      bilingual speakers. Consistent with a specific neuroprotective effect of
      bilingualism, region of interest analyses showed a significant positive
      correlation between naming performance in the second language and GMV in this
      region. The effect appears to be bilateral though because there was a
      nonsignificantly different effect of naming performance on GMV in the right
      temporal pole. Our data emphasize the vulnerability of the temporal pole to
      normal aging and the value of bilingualism as both a general and specific
      protective factor to GMV decreases in healthy aging.

PMID- 24721822
TI  - Immune recognition of Onchocerca volvulus proteins in the human host and animal
      models of onchocerciasis.
AB  - Onchocerca volvulus is a tissue-dwelling, vector-borne nematode parasite of
      humans and is the causative agent of onchocerciasis or river blindness. Natural
      infections of BALB/c mice with Litomosoides sigmodontis and of cattle with
      Onchocerca ochengi were used as models to study the immune responses to O.
      volvulus-derived recombinant proteins (OvALT-2, OvNLT-1, Ov103 and Ov7). The
      humoral immune response of O. volvulus-infected humans against OvALT-2, OvNLT-1
      and Ov7 revealed pronounced immunoglobulin G (IgG) titres which were, however,
      significantly lower than against the lysate of O. volvulus adult female worms.
      Sera derived from patients displaying the hyperreactive form of onchocerciasis
      showed a uniform trend of higher IgG reactivity both to the single proteins and
      the O. volvulus lysate. Sera derived from L. sigmodontis-infected mice and from
      calves exposed to O. ochengi transmission in a hyperendemic area also contained
      IgM and IgG1 specific for O. volvulus-derived recombinant proteins. These results
      strongly suggest that L. sigmodontis-specific and O. ochengi-specific
      immunoglobulins elicited during natural infection of mice and cattle cross
      reacted with O. volvulus-derived recombinant antigens. Monitoring O. ochengi
      infected calves over a 26-month period, provided a comprehensive kinetic of the
      humoral response to infection that was strictly correlated with parasite load and
      occurrence of microfilariae. 

PMID- 24721823
TI  - Prognostic value of paraoxonase 1 in patients undergoing coronary artery bypass
      grafting surgery.
AB  - BACKGROUND: The aim of this study was to evaluate whether -108C/T polymorphism of
      the paraoxonase 1 (PON1) gene and the plasma enzyme activity are risk factors for
      adverse cardiac events after coronary artery bypass grafting (CABG). MATERIAL AND
      METHODS: Seventy-one patients with coronary heart disease (CHD) undergoing CABG
      were enrolled in the study. Genomic DNA was extracted from the venous blood using
      the Gen EluteTM Blood Genomic DNA kit (Sigma) according to the manufacturer's
      instructions. PON1 activity was measured in 50 mM glycine/NaOH buffer (pH 10.5)
      containing 1.0 mM paraoxon, and 1.0mM CaCl2. RESULTS: The mean PON1 activity
      toward paraoxon and toward phenyl acetate was equal (166.5 +/- 86.9 U/ml and 96.0
      +/- 47.2 U/ml, respectively) in patients with CHD. The -108C/T polymorphism of
      PON1 gene was tested. In CABG patients, PON1 activities in dependence on
      genotypes were significantly different and equalled 266.2 +/- 117.9 U/ml for CC,
      178.8 +/- 64.7 U/ml for CT, and 98.9 +/- 59.2 U/ml for TT genotype. Patients with
      PON1 activity lower than 193.5 U/ml exhibited significantly increased risk of a
      serious cardiac event in comparison with patients with PON1 activity higher or
      equal to this value (p=0.03). Additionally, TT genotype was significantly
      associated with shorter time of event-free survival in comparison with CT and CC
      genotypes (p=0.009). CONCLUSIONS: The PON1 polymorphism and enzyme plasma
      activity are associated with CHD occurrence. High PON1 activity connected with
      the presence of CC and CT genotypes decreases the recurrence of symptoms of
      coronary heart disease and improve prognosis after CABG.

PMID- 24721821
TI  - Medial temporal atrophy in early and late-onset Alzheimer's disease.
AB  - Late-onset and early-onset Alzheimer's disease (LOAD, EOAD) affect different
      neural systems and may be separate nosographic entities. The most striking
      differences are in the medial temporal lobe, severely affected in LOAD and
      relatively spared in EOAD. We assessed amygdalar morphology and volume in 18 LOAD
      and 18 EOAD patients and 36 aged-matched controls and explored their relationship
      with the hippocampal volume. Three-dimensional amygdalar shape was reconstructed
      with the radial atrophy mapping technique, hippocampal volume was measured using
      a manual method. Atrophy was greater in LOAD than EOAD: 25% versus 17% in the
      amygdala and 20% versus 13% in the hippocampus. In the amygdala, LOAD showed
      significantly greater tissue loss than EOAD in the right dorsal central, lateral,
      and basolateral nuclei (20%-30% loss, p < 0.03), all known to be connected to
      limbic regions. In LOAD but not EOAD, greater hippocampal atrophy was associated
      with amygdalar atrophy in the left dorsal central and medial nuclei (r = 0.6, p <
      0.05) also part of the limbic system. These findings support the notion that
      limbic involvement is a prominent feature of LOAD but not EOAD.

PMID- 24721824
TI  - In vivo reflectance confocal microscopy features of cutaneous microcirculation
      and epidermal and dermal changes in diffuse systemic sclerosis and correlation
      with histological and videocapillaroscopic findings.
AB  - BACKGROUND: Videocapillaroscopy of the nail fold is the current gold standard to
      assess progressive changes of the capillary network in patients with systemic
      sclerosis (SSc). Reflectance confocal microscopy (RCM) is a non-invasive optical
      imaging tool that allows in vivo visualization of the skin structures and
      cutaneous microcirculation. OBJECTIVE: To investigate qualitative and
      quantitative changes of the cutaneous microcirculation and dermal-epidermal
      alterations of SSc patients by RCM and to correlate the images with findings of
      videocapillaroscopy and histology. METHODS: Ten patients affected by diffuse-type
      SSc with skin involvement and 10 healthy controls were enrolled. All subjects
      underwent RCM of the dorsal and ventral surfaces of the middle third of the left
      forearm and nailfold videocapillaroscopy. Skin biopsies for histological and
      immunohistochemical investigations were taken from 5 patients and 2 healthy
      controls. RESULTS: At RCM observation, the diameter, perimeter and area of
      cutaneous capillaries were significantly increased in comparison to healthy
      controls, as histologically confirmed, whereas blood flow speed was significantly
      slower. Videocapillaroscopy showed a pathologic pattern of disease activity in 8
      SSc patients and was non-specific in the remaining 2. In addition, RCM showed
      epidermal atrophy, flattening of rete ridges and dermal fibrosis in 7 SSc
      patients with long-standing disease but not in 3 patients with a recent onset.
      CONCLUSION: RCM provides measurable morphological and functional findings of
      microcirculation in patients suffering from diffuse-type SSc. These findings can
      integrate with, but not substitute, those provided by standard
      videocapillaroscopy. In addition, unlike videocapillaroscopy, RCM allows the
      investigation of epidermal and dermal changes.

PMID- 24721825
TI  - Innervation mapping of the hind paw of the rat using Evans Blue extravasation,
      Optical Surface Mapping and CASAM.
AB  - BACKGROUND: Although numerous studies investigate sensory regeneration and
      reinnervation of the hind paw of the rat after nerve damage, no comprehensive
      overview of its normal innervation is present in literature. The Evans Blue
      extravasation technique is a well-known technique to study patterns of skin
      innervation. This technique has been performed differently by various groups but
      was never used to study the entire skin innervation in rats' hind paw including
      all three branches of the sciatic nerve and the saphenous nerve in detail. NEW
      METHOD: In this paper, we have used the Evans Blue extravasation technique to
      chart the skin areas innervated by the sural, peroneal, tibial and/or saphenous
      nerves, which together innervate the entire hind paw of the rat, and use a new
      technique to analyze the distribution, overlap and variability of the results.
      The technique is based on analysis of whole hind paws using Optical Surface
      Mapping (OSM) in combination with the Computer Assisted Surgical Anatomy Mapping
      (CASAM) technology. RESULTS: While the plantar hind paw is mainly innervated by
      the tibial nerve, the dorsal hind paw is supplied by the sural, peroneal and the
      saphenous nerve. COMPARISON WITH EXISTING METHODS: Although our results basically
      concur with the general nerve-specific innervation of the rat hind paw, they show
      considerable detail in their areas of overlap as well as in the amount of
      variability between animals. CONCLUSION: These results will be invaluable to
      study and evaluate patterns of innervation and reinnervation of intact and
      damaged nerve fibers.

PMID- 24721826
TI  - Napsin A is a specific marker for ovarian clear cell adenocarcinoma.
AB  - Ovarian clear cell adenocarcinoma has a relatively poor prognosis among the
      ovarian cancer subtypes because of its high chemoresistance. Differential
      diagnosis of clear cell adenocarcinoma from other ovarian surface epithelial
      tumors is important for its treatment. Napsin A is a known diagnostic marker for
      lung adenocarcinoma, and expression of napsin A is reported in a certain portion
      of thyroid and renal carcinomas. However, napsin A expression in ovarian surface
      epithelial tumors has not previously been examined. In this study,
      immunohistochemical analysis revealed that in 71 of 86 ovarian clear cell
      adenocarcinoma patients (83%) and all of the 13 patients with ovarian clear cell
      adenofibroma, positive napsin A staining was evident. No expression was observed
      in 30 serous adenocarcinomas, 11 serous adenomas or borderline tumors, 19
      endometrioid adenocarcinomas, 22 mucinous adenomas or borderline tumors, 10
      mucinous adenocarcinomas, or 3 yolk sac tumors of the ovary. Furthermore,
      expression of napsin A was not observed in the normal surface epithelium of the
      ovary, epithelia of the fallopian tubes, squamous epithelium, endocervical
      epithelium, or the endometrium of the uterus. Therefore, we propose that napsin A
      is another sensitive and specific marker for distinguishing ovarian clear cell
      tumors (especially adenocarcinomas) from other ovarian tumors. 

PMID- 24721827
TI  - Effects of topical application of a recombinant staphylococcal enterotoxin A on
      DNCB and dust mite extract-induced atopic dermatitis-like lesions in a murine
      model.
AB  - BACKGROUND: Atopic dermatitis (AD) is a chronic inflammatory skin disease with
      biphasic T cell-mediated abnormalities. Staphylococcal superantigens contribute
      to the exacerbation of inflammation in AD. The underlying immunopathological
      mechanisms are not fully understood. OBJECTIVE: To determine whether epicutaneous
      application of recombinant staphylococcal enterotoxin A (rSEA) would exacerbate
      AD-like allergic inflammation induced by 2, 4-dinitrochlorobenzene (DNCB) and
      house dust mite extract (Dermatophagoides farinae extract, DFE) in a murine
      model. MATERIALS AND METHODS: We first established an AD-like model using BALB/c
      mice exposed to DNCB/DFE on the ear. Next, Staphylococcus (S.) aureus or rSEA
      were topically applied to the mice. We evaluated the clinical and
      histopathological features of the animals. Serum immunoglobulin levels were also
      measured. In addition, real-time PCR analysis of cytokines produced by T cell
      subsets in the ears was conducted. RESULTS: Mice treated with S. aureus and rSEA
      had more severe clinical symptoms, including increased mean dermatitis scores and
      ear thickness, compared to animals with only AD-like lesions. Total IgE, IgG2a
      and serum histamine levels were increased in all groups except the normal control
      group. The S. aureus- and rSEA-treated groups showed increased levels of
      cytokines such as IL-4, IL-13, INF-gamma, IL-17, and IL-18. In particular,
      increased cytokine expression was more conspicuous in the rSEA-treated group than
      in mice exposed to S. aureus. CONCLUSION: The results of this study showed that
      topical exposure to rSEA as well as SEA-producing S. aureus aggravate atopic skin
      inflammation. This may be associated with the induction of a mixed Th1/Th2 type
      dermatitis.

PMID- 24721828
TI  - Synthesis and antiviral activity of a novel glycosyl sulfoxide against classical
      swine fever virus.
AB  - A novel compound-2",3",4",6"-tetra-O-acetyl-beta-d-galactopyranosyl-(1->4)
      2',3',6'-tri-O-acetyl-1-thio-beta-d-glucopyranosyl-(5-nitro-2-pyridyl) sulfoxide
      designated GP6 was synthesized and assayed for cytotoxicity and in vitro
      antiviral properties against classical swine fever virus (CSFV) in this study. We
      showed that the examined compound effectively arrested CSFV growth in swine
      kidney cells (SK6) at a 50% inhibitory concentration (IC50) of 5 +/- 0.12 MUg/ml
      without significant toxicity for mammalian cells. Moreover, GP6 reduced the viral
      E2 and E(rns) glycoproteins expression in a dose-dependent manner. We have
      excluded the possibility that the inhibitor acts at the replication step of virus
      life cycle as assessed by monitoring of RNA level in cells and culture medium of
      SK6 cells after single round of infection as a function of GP6 treatment. Using
      recombinant E(rns) and E2 proteins of classical swine fever virus produced in
      baculovirus expression system we have demonstrated that GP6 did not influence
      glycoprotein production and maturation in insect cells. In contrast to mammalian
      glycosylation pathway, insect cells support only the ER-dependent early steps of
      this process. Therefore, we concluded that the late steps of glycosylation
      process are probably the main targets of GP6. Due to the observed antiviral
      effect accompanied by low cytotoxicity, this inhibitor represents potential
      candidate for the development of antiviral agents for anti-flavivirus therapy.
      Further experiments are needed for investigating whether this compound can be
      used as a safe antiviral agent against other viruses from unrelated groups.

PMID- 24721829
TI  - Synthesis, beta-haematin inhibition, and in vitro antimalarial testing of
      isocryptolepine analogues: SAR study of indolo[3,2-c]quinolines with various
      substituents at C2, C6, and N11.
AB  - A series of indolo[3,2-c]quinolines were synthesized by modifying the side chains
      of the omega-aminoalkylamines at the C6 position and introducing substituents at
      the C2 position, such as F, Cl, Br, Me, MeO and NO2, and a methyl group at the
      N11 position for an SAR study. The in vitro antiplasmodial activities of the
      derivative agents against two different strains (CQS: NF54 and CQR: K1) and the
      cytotoxic activity against normal L6 cells were evaluated. The test results
      showed that compounds 6k and 6l containing the branched methyl groups of 3
      aminopropylamino at C6 with a Cl atom at C2 exhibited a very low cytotoxicity
      with IC50 values above 4000 nM, high antimalarial activities with IC50 values of
      about 11 nM for CQS (NF54), IC50 values of about 17 nM for CQR (K1), and RI
      resistance indices of 1.6. Furthermore, the compounds were tested for beta
      haematic inhibition, and QSAR revealed an interesting linear correlation between
      the biological activity of CQS (NF54) and three contributing factors, namely
      solubility, hydrophilic surface area, and beta-haematin inhibition for this
      series. In vivo testing of 6l showed a reduction in parasitaemia on day 4 with an
      activity of 38%.

PMID- 24721830
TI  - Synthesis and in vitro evaluation of bis-quaternary 2-(hydroxyimino)-N-(pyridin-3
      yl)acetamide derivatives as reactivators against sarin and VX inhibited human
      acetylcholinesterase (hAChE).
AB  - A series of bis-quaternary pyridinium derivatives 3a-3i of 2-(hydroxyimino)-N
      (pyridin-3-yl)acetamide (2) have been synthesized. The synthesized pyridinium
      compounds have an amide group in conjugation to the oxime moiety. These compounds
      were evaluated in vitro for their reactivation efficacy against organophosphorus
      (OP) nerve agents (NAs) (sarin and VX) inhibited human erythrocyte ghost
      acetylcholinesterase (hAChE) and compared with the reactivation efficacy of 2-PAM
      and obidoxime. The pKa values of the synthesized compounds were found closer to
      the pKa values of 2- and 4-pyridinium oxime reactivators such as 2-PAM and
      obidoxime. Some of the compounds have shown better reactivation efficacy than 2
      PAM, and obidoxime against sarin and VX inhibited AChE. 

PMID- 24721831
TI  - Radiosyntheses and in vivo evaluation of carbon-11 PET tracers for PDE10A in the
      brain of rodent and nonhuman primate.
AB  - The radiosyntheses and in vivo evaluation of four carbon-11 labeled quinoline
      group-containing radioligands are reported here. Radiolabeling of [(11)C]1-4 was
      achieved by alkylation of their corresponding desmethyl precursors with
      [(11)C]CH3I. Preliminary biodistribution evaluation in Sprague-Dawley rats
      demonstrated that [(11)C]1 and [(11)C]2 had high striatal accumulation (at peak
      time) for [(11)C]1 and [(11)C]2 were 6.0-fold and 4.5-fold at 60 min,
      respectively. Following MP-10 pretreatment, striatal uptake in rats of [(11)C]1
      and [(11)C]2 was reduced, suggesting that the tracers bind specifically to
      PDE10A. MicroPET studies of [(11)C]1 and [(11)C]2 in nonhuman primates (NHP) also
      showed good tracer retention in the striatum with rapid clearance from non-target
      brain regions. Striatal uptake (SUV) of [(11)C]1 reached 1.8 at 30 min with a 3.5
      fold striatum:cerebellum ratio. In addition, HPLC analysis of solvent extracts
      from NHP plasma samples suggested that [(11)C]1 had a very favorable metabolic
      stability. Our preclinical investigations suggest that [(11)C]1 is a promising
      candidate for quantification of PDE10A in vivo using PET.

PMID- 24721832
TI  - Synthesis of a terphenyl substituted 4-aza-2,3-didehydropodophyllotoxin analogues
      as inhibitors of tubulin polymerization and apoptosis inducers.
AB  - A series of terphenyl based 4-aza-2,3-didehydropodophyllotoxin conjugates (8a-r)
      were synthesized by a straightforward one-step multicomponent synthesis that
      demonstrated anticancer activity against five human cancer cell lines (lung,
      colon, renal, prostate and cervical). All the tested compounds showed potent
      anticancer activity with IC50 values ranging from 0.87 to 16.59 MUM. Among them
      compounds 8n and 8p showed significant anticancer activity in lung cancer cells
      with IC50 values 0.91 and 0.87 MUM, respectively. Flow cytometric analysis
      revealed that these compounds induced cell cycle arrest in G2/M phase in A549
      cell line leading to caspase-3 dependent apoptotic cell death. The tubulin
      polymerization assay and immunofluorescence analysis showed that these compounds
      effectively inhibit microtubule assembly at both molecular and cellular levels in
      A549 cells. Further, Hoechst staining, DNA fragmentation analysis also suggested
      that these compounds induced cell death by apoptosis. Overall, the current study
      demonstrated that the synthesis of terphenyl based 4-aza-2,3
      didehydropodophyllotoxin conjugates as promising anticancer agents with G2/M cell
      cycle arrest and apoptotic-inducing activities via targeting tubulin.

PMID- 24721833
TI  - Synthesis and cellular characterization of novel isoxazolo- and
      thiazolohydrazinylidene-chroman-2,4-diones on cancer and non-cancer cell growth
      and death.
AB  - Coumarins are extensively studied anticoagulants that exert additional effects
      such as anticancerogenic and even anti-inflammatory. In order to find new drugs
      with anticancer activities, we report here the synthesis and the structural
      analysis of new coumarin derivatives which combine the coumarin core and five
      member heterocycles in hydrazinylidene-chroman-2,4-diones. The derivatives were
      prepared by derivatization of the appropriate heterocyclic amines which were used
      as electrophiles to attack the coumarin ring. The structures were characterized
      by spectroscopic techniques including IR, NMR, 2D-NMR and MS. These derivatives
      were further characterized especially in terms of a potential cytotoxic and
      apoptogenic effect in several cancer cell lines including the breast and prostate
      cancer cell lines MCF-7, MDA-MB-231, PC-3, LNCaP, and the monocytic leukemia cell
      line U937. Cell viability was determined after 48 h and 72 h of treatment with
      the novel compounds by MTT assay and the 50% inhibitory concentrations (EC50
      values) were determined. Out of the 8 novel compounds screened for reduced cell
      viability, 4c, 4d and 4e were found to be the most promising and effective ones
      having EC50 values that were several fold reduced when compared to the reference
      substance 4-hydroxycoumarin. However, the effects were cancer cell line
      dependent. The breast cancer MDA-MB-231 cells, the prostate cancer LNCaP cells,
      and U937 cells were most sensitive, MCF-7 cells were less sensitive, and PC-3
      cells were more resistant. Reduced cell viability was accompanied by increased
      apoptosis as shown by PARP-1 cleavage and reduced activity of the survival
      protein kinase Akt. In summary, this study has identified three novel coumarin
      derivatives that in comparison to 4-hydroxycoumarin have a higher efficiency to
      reduce cancer cell viability and trigger apoptosis and therefore may represent
      interesting novel drug candidates.

PMID- 24721835
TI  - A familial disorder of altered DNA-methylation.
AB  - BACKGROUND: In a subset of imprinting disorders caused by epimutations, multiple
      imprinted loci are affected. Familial occurrence of multilocus imprinting
      disorders is rare. PURPOSE/OBJECTIVE: We have investigated the clinical and
      molecular features of a familial DNA-methylation disorder. METHODS: Tissues of
      affected individuals and blood samples of family members were investigated by
      conventional and molecular karyotyping. Sanger sequencing and RT-PCR of
      imprinting-associated genes (NLRP2, NLRP7, ZFP57, KHDC3L, DNMT1o), exome
      sequencing and locus-specific, array-based and genome-wide technologies to
      determine DNA-methylation were performed. RESULTS: In three offspring of a
      healthy couple, we observed prenatal onset of severe growth retardation and
      dysmorphism associated with altered DNA-methylation at paternally and maternally
      imprinted loci. Array-based analyses in various tissues of the offspring
      identified the DNA-methylation of 2.1% of the genes in the genome to be
      recurrently altered. Despite significant enrichment of imprinted genes (OR 9.49),
      altered DNA-methylation predominately (90.2%) affected genes not known to be
      imprinted. Sequencing of genes known to cause comparable conditions and exome
      sequencing in affected individuals and their ancestors did not unambiguously
      point to a causative gene. CONCLUSIONS: The family presented herein suggests the
      existence of a familial disorder of DNA-methylation affecting imprinted but also
      not imprinted gene loci potentially caused by a maternal effect mutation in a
      hitherto not identified gene.

PMID- 24721834
TI  - A meta-analysis identifies adolescent idiopathic scoliosis association with LBX1
      locus in multiple ethnic groups.
AB  - BACKGROUND: Adolescent idiopathic scoliosis (AIS) is a common rotational
      deformity of the spine that presents in children worldwide, yet its etiology is
      poorly understood. Recent genome-wide association studies (GWAS) have identified
      a few candidate risk loci. One locus near the chromosome 10q24.31 LBX1 gene (OMIM
      #604255) was originally identified by a GWAS of Japanese subjects and replicated
      in additional Asian populations. To extend this result, and to create larger AIS
      cohorts for the purpose of large-scale meta-analyses in multiple ethnicities, we
      formed a collaborative group called the International Consortium for Scoliosis
      Genetics (ICSG). METHODS: Here, we report the first ICSG study, a meta-analysis
      of the LBX1 locus in six Asian and three non-Asian cohorts. RESULTS: We find
      significant evidence for association of this locus with AIS susceptibility in all
      nine cohorts. Results for seven cohorts containing both genders yielded P=1.22*10
      43 for rs11190870, and P=2.94*10-48 for females in all nine cohorts. Comparing
      the regional haplotype structures for three populations, we refined the
      boundaries of association to a ~25 kb block encompassing the LBX1 gene. The LBX1
      protein, a homeobox transcription factor that is orthologous to the Drosophila
      ladybird late gene, is involved in proper migration of muscle precursor cells,
      specification of cardiac neural crest cells, and neuronal determination in
      developing neural tubes. CONCLUSIONS: Our results firmly establish the LBX1
      region as the first major susceptibility locus for AIS in Asian and non-Hispanic
      white groups, and provide a platform for larger studies in additional ancestral
      groups.

PMID- 24721836
TI  - PrP overdrive: does inhibition of alpha-cleavage contribute to PrP(C) toxicity
      and prion disease?
AB  - Knockout of the cellular prion protein (PrP(C)) in mice is tolerated, as is
      complete elimination of the protein's N-terminal domain. However, deletion of
      select short segments between the N- and C-terminal domains is lethal. How can
      one reconcile this apparent paradox? Research over the last few years
      demonstrates that PrP(C) undergoes alpha-cleavage in the vicinity of residue 109
      (mouse sequence) to release the bioactive N1 and C1 fragments. In biophysical
      studies, we recently characterized the action of relevant members of the ADAM (A
      Disintegrin And Metalloproteinase) enzyme family (ADAM8, 10, and 17) and found
      that they all produce alpha-cleavage, but at 3 distinct cleavage sites, with
      proteolytic efficiency modulated by the physiologic metals copper and zinc.
      Remarkably, the shortest lethal deletion segment in PrP(C) fully encompasses the
      3 alpha-cleavage sites. Analysis of all reported PrP(C) deletion mutants suggests
      that elimination of alpha-cleavage, coupled with retention of the protein's N
      terminal residues, segments 23-31 and longer, confers the lethal phenotype.
      Interestingly, these N-terminal residues are implicated in the activation of
      several membrane proteins, including synaptic glutamate receptors. We propose
      that alpha-cleavage is a general mechanism essential for downregulating PrP(C)'s
      intrinsic activity, and that blockage of proteolysis leads to constitutively
      active PrP(C) and consequent dyshomeostasis. 

PMID- 24721837
TI  - A novel ELISA system for simultaneous detection of six subclasses of anti
      phospholipid antibodies for prediction of thrombotic complications among SLE
      patients.
AB  - BACKGROUND: Anti-phospholipid antibodies (aPLs) are frequently associated with
      arterial and/or venous thromboembolic complications and recurrent fetal loss in
      patients with systemic lupus erythematosus (SLE). We recently reported that the
      clinical picture of SLE apparently depends on subclasses of aPLs in the patient's
      sera, but the contribution of each subclass remains uncertain. METHODS: We newly
      developed an ELISA system for simultaneous detection of six specific categories
      of aPLs: anti-cardiolipin (aCL), anti-beta2-glycoprotein I (abeta2GPI), anti
      cardiolipin/beta2-glycoprotein I (aCL/beta2GPI), anti-phosphatidylserine (aPS),
      anti-prothrombin (aPT), and anti-phosphatidylserine/prothrombin (aPS/PT). They
      were measured in 331 patients with SLE including 63 patients with arterial
      thromboembolic complications, 64 with venous thromboembolic complications, and 43
      with recurrent fetal loss. Lupus anticoagulant (LA) activity in their plasma was
      measured according to the guidelines recommended by the Subcommittee on Lupus
      Anticoagulant/Phospholipid-Dependent Antibodies. RESULTS: Multivariate logistic
      analysis revealed that the concentration of aPS/PT was most closely associated
      with arterial thrombosis. In contrast, the concentration of abeta2GPI was most
      closely related to venous thrombosis. Furthermore, both aCL/beta2GPI and aPS/PT
      were independently associated with episodes of recurrent fetal loss. Regarding
      the relation between APLs and LA activity, aPS/PT, followed by abeta2GPI and aPT,
      showed the closest association with the presence of LA activity. CONCLUSIONS:
      Anti-phospholipid syndrome in patients with SLE can be classified by antigenic
      specificities of their aPLs as to their susceptibility to arterial and/or venous
      thromboembolic complications or obstetric complications.

PMID- 24721838
TI  - A population health approach to reducing observational intensity bias in health
      risk adjustment: cross sectional analysis of insurance claims.
AB  - OBJECTIVE: To compare the performance of two new approaches to risk adjustment
      that are free of the influence of observational intensity with methods that
      depend on diagnoses listed in administrative databases. SETTING: Administrative
      data from the US Medicare program for services provided in 2007 among 306 US
      hospital referral regions. DESIGN: Cross sectional analysis. PARTICIPANTS: 20%
      sample of fee for service Medicare beneficiaries residing in one of 306 hospital
      referral regions in the United States in 2007 (n = 5,153,877). MAIN OUTCOME
      MEASURES: The effect of health risk adjustment on age, sex, and race adjusted
      mortality and spending rates among hospital referral regions using four indices:
      the standard Centers for Medicare and Medicaid Services--Hierarchical Condition
      Categories (HCC) index used by the US Medicare program (calculated from diagnoses
      listed in Medicare's administrative database); a visit corrected HCC index (to
      reduce the effects of observational intensity on frequency of diagnoses); a
      poverty index (based on US census); and a population health index (calculated
      using data on incidence of hip fractures and strokes, and responses from a
      population based annual survey of health from the Centers for Disease Control and
      Prevention). RESULTS: Estimated variation in age, sex, and race adjusted
      mortality rates across hospital referral regions was reduced using the indices
      based on population health, poverty, and visit corrected HCC, but increased using
      the standard HCC index. Most of the residual variation in age, sex, and race
      adjusted mortality was explained (in terms of weighted R2) by the population
      health index: R2=0.65. The other indices explained less: R2=0.20 for the visit
      corrected HCC index; 0.19 for the poverty index, and 0.02 for the standard HCC
      index. The residual variation in age, sex, race, and price adjusted spending per
      capita across the 306 hospital referral regions explained by the indices (in
      terms of weighted R2) were 0.50 for the standard HCC index, 0.21 for the
      population health index, 0.12 for the poverty index, and 0.07 for the visit
      corrected HCC index, implying that only a modest amount of the variation in
      spending can be explained by factors most closely related to mortality. Further,
      once the HCC index is visit corrected it accounts for almost none of the residual
      variation in age, sex, and race adjusted spending. CONCLUSION: Health risk
      adjustment using either the poverty index or the population health index
      performed substantially better in terms of explaining actual mortality than the
      indices that relied on diagnoses from administrative databases; the population
      health index explained the majority of residual variation in age, sex, and race
      adjusted mortality. Owing to the influence of observational intensity on
      diagnoses from administrative databases, the standard HCC index over-adjusts for
      regional differences in spending. Research to improve health risk adjustment
      methods should focus on developing measures of risk that do not depend on
      observation influenced diagnoses recorded in administrative databases.

PMID- 24721840
TI  - With a licence to doubt.

PMID- 24721839
TI  - C-kit induces epithelial-mesenchymal transition and contributes to salivary
      adenoid cystic cancer progression.
AB  - Epithelial-mesenchymal transition (EMT) is associated with salivary adenoid
      cystic cancer (ACC) progression and metastasis. Here, we report that ectopic
      overexpression of c-kit in ACC cell lines is sufficient for acquisition of
      mesenchymal traits, enhanced cell invasion, along with stem cell properties
      defined by the presence of a CD133+/CD44+ cell subpopulation. c-kit positively
      regulated expression of known EMT inducers, also activating TGF-beta to
      contribute to EMT. c-kit itself was induced by TGF-beta in ACC cell lines and
      required for TGF-beta-induced EMT. Xenograft experiments showed that c-kit
      cooperated with oncogenic Ras to promote tumorigenesis in vivo. Finally, in human
      specimens of ACC, we found that c-kit was abnormally overexpressed and correlated
      with the prognosis of ACC. Our findings define an important function for c-kit in
      ACC progression by orchestrating EMT, and they implicate this gene product as a
      marker of poor prognosis in this disease. 

PMID- 24721841
TI  - Tendency to fall in older people.

PMID- 24721842
TI  - [Cardiovascular risk in ADHD treatment in children].

PMID- 24721843
TI  - [Re: Physicians' private referral practices].

PMID- 24721844
TI  - [K. Hytten replies].

PMID- 24721845
TI  - [Re: Woman in her 30s with chronic fatigue].

PMID- 24721846
TI  - [E.H. Helskog and colleagues reply].

PMID- 24721847
TI  - [Re: Chiropractic education in Norway now!].

PMID- 24721848
TI  - [Re: Chiropractic education in Norway now!].

PMID- 24721849
TI  - [S. Evensen replies].

PMID- 24721850
TI  - [Re: Prenatal diagnosis with blood tests].

PMID- 24721853
TI  - Better legal protection of doctoral research fellows.

PMID- 24721854
TI  - [Unacceptable shortage of carbimazole].

PMID- 24721855
TI  - [It's between your ears?].

PMID- 24721857
TI  - Medical findings in an interdisciplinary geriatric outpatient clinic specialising
      in falls.
AB  - BACKGROUND: Falls are common among elderly people, leading to increased morbidity
      and reduced quality of life. A broad-based interdisciplinary study, for example
      in an outpatient clinic specialising in falls, has been recommended in light of
      the multiple and complex causes that tend to be involved. At present there are
      few outpatient clinics in Norway specialising in falls, and no data from such
      studies have yet been published. MATERIAL AND METHOD: The information stems from
      111 patients at the Fallpoliklinikken, Oslo University Hospital, from its
      establishment in 2008 until 2011. An interdisciplinary study was undertaken by a
      nurse, a doctor and a physiotherapist. Further investigations and measures were
      proposed on the basis of individual risk factors. RESULTS: The patient group had
      a number of known risk factors for falls. The most frequently identified risk
      factors included orthostatism (26 of 110 patients, 24%), vitamin D deficiency (14
      of 79 patients, 18%) and carotid sinus hypersensitivity (6 of 55 patients
      examined, 11%). Rare, but significant findings included colon cancer, subdural
      haematoma (one case of each) and normal pressure hydrocephalus (two cases). The
      most frequent measures for preventing new falls included exercise/physiotherapy
      (close to all patients), adjustment of medications (25 patients, 23%) and
      implantation of a pacemaker (six patients, 5%). INTERPRETATION: Falls among
      elderly people have varying and complex causes and a serious underlying pathology
      may manifest itself as a tendency to fall. This testifies to the importance of a
      thorough interdisciplinary study of falls.

PMID- 24721858
TI  - [Cardiovascular risk assessment for the use of ADHD drugs in children].
AB  - BACKGROUND: Drug therapy for ADHD (Attention Deficit Hyperactivity Disorder) has
      generally been regarded as safe. ECG screening of healthy children and
      adolescents before initiating this type of treatment appears to be usual in
      Norway, despite recommendations that ECGs should only be undertaken in
      individuals who are at risk. The purpose of this article is to clarify relevant
      guidelines for cardiovascular risk assessment for the use of ADHD drugs in
      children and adolescents, as well as to propose practical recommendations.
      METHOD: The article is based on a literature search in PubMed completed on 1
      October 2013, and on the author's own clinical experience and discretionary
      assessments. RESULTS: The use of CNS stimulants and atomoxetine is associated
      with a slight rise in blood pressure and pulse rate, as well as small changes in
      QT interval. A small percentage of patients (5-10%) experience a clinically
      significant rise in blood pressure and pulse rate. Sudden death does not appear
      to occur more frequently in children and adolescents taking ADHD drugs in
      therapeutic doses than in children and adolescents who do not use such drugs.
      There is little knowledge available on the long-term effects of ADHD drugs on the
      cardiovascular system of otherwise healthy individuals, or on the risk related to
      the use of ADHD drugs in children and adolescents with cardiac disease. The drugs
      are thought to increase the risk of sudden cardiac death in some arrhythmia
      syndromes. INTERPRETATION: Our assessment is that caution should be exercised in
      the use of ADHD drugs in children with potentially dangerous cardiac arrhythmias.
      We recommend clinical examination and a thorough medical history review in order
      to identify individuals at risk before initiating drug therapy, and also suggest
      that it is not necessary for healthy children to be given an ECG examination
      before introducing ADHD drugs. In children with known cardiac disease, arrhythmia
      or risk factors for cardiac disease, ADHD treatment should be undertaken in
      consultation with a medical specialist with competence in pediatric cardiology.

PMID- 24721859
TI  - [A knot on the aquarium owner's hand].

PMID- 24721860
TI  - [Liver cyst from the East].

PMID- 24721861
TI  - An elderly woman with unexplained falls and "tingling sensations in the head".

PMID- 24721862
TI  - [Biased judgement about whiplash from the Supreme Court].

PMID- 24721863
TI  - [Vitamin D--how much is enough, and is more better for your Health?].

PMID- 24721864
TI  - [How to measure vitamin D status?].

PMID- 24721865
TI  - [Throat disease in the periphery of Europe: the introduction of diphteria
      antitoxin in Romsdal county].
AB  - Diphteria played a key role in establishing the bacteriological model for
      explaining infectious disease. This understanding of bacteriological factors
      spurred research that culminated in the development of diphteria antitoxin, the
      first effective therapeutic cure for an epidemiological disease. Prior to the
      introduction of antitoxin, isolation and disinfection were regarded as the key
      defences against diphteria. The opportunity to combine antitoxin therapy with
      existing methods for combatting the disease was a key factor for the rapid spread
      of the antitoxin. Diphteria antitoxin was first used in Romsdal county in 1895.
      Initially the serum had to be ordered from manufacturers abroad, which restricted
      its application in the district. Few available doctors and long transport routes
      were reasons that prevented the antitoxin from reaching its full potential.
      Industrial manufacturing methods were an obstacle to serum production in
      peripheral areas. In Norway, production of serum gradually got underway in
      Kristiania, which was one factor that caused mortality from diphteria to decline
      faster there than in other parts of the country. In this article we will
      elucidate the relationship between the centre and the periphery in the spread of
      medical advances by studying the implementation of diphteria antitoxin in Romsdal
      county.

PMID- 24721866
TI  - [Women in academia--a threat to men?].

PMID- 24721867
TI  - [Heavy losses with deep puzzles].

PMID- 24721868
TI  - [Why poor health?].

PMID- 24721882
TI  - Maternal obesity and diabetes may cause DNA methylation alteration in the
      spermatozoa of offspring in mice.
AB  - BACKGROUND: The adverse effects on offspring of diabetic and/or obese mothers can
      be passed to the next generation. However, the mechanisms behind this are still
      unclear. Epigenetics may play a key role during this process. METHODS: To confirm
      the hypothesis, we investigated the DNA methylation of several imprinted genes in
      spermatozoa of offspring from diabetic and/or obese mothers utilizing
      streptozotocin (STZ)- and high-fat-diet (HFD)-induced mouse models. RESULTS: We
      found that the DNA methylation of Peg3 was significantly increased in spermatozoa
      of offspring of obese mothers compared to that in spermatozoa of offspring of
      normal mothers. The DNA methylation of H19 was significantly higher in
      spermatozoa of offspring of diabetic mothers than that in spermatozoa of
      offspring of non-diabetic mothers. CONCLUSIONS: These results indicate that pre
      gestational diabetes and/or obesity can alter DNA methylation in offspring
      spermatozoa.

PMID- 24721884
TI  - Anatomical variation of the extracranial course of the optic nerve in the floor
      of the sphenoid sinus.

PMID- 24721883
TI  - Treatment of recalcitrant erythrodermic psoriasis with ustekinumab.

PMID- 24721885
TI  - IgA nephropathy with minimal change disease.
AB  - BACKGROUND AND OBJECTIVES: Patients with IgA nephropathy typically present with
      hematuria and subnephrotic proteinuria. Nephrotic syndrome is uncommon in IgA
      nephropathy, and when present, it is usually associated with severe histologic
      features, such as endocapillary proliferation, segmental sclerosis, and crescent
      formation. Rarely, patients with IgA nephropathy present with nephrotic syndrome
      and only mild mesangial disease. This study sought to better characterize these
      patients. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: A retrospective review
      of cases of IgA nephropathy diagnosed from 2004 to 2011 identified patients with
      nephrotic range proteinuria and histologically mild IgA nephropathy.
      Specifically, using the Oxford Classification of IgA Nephropathy, we identified
      cases that lacked endocapillary proliferation or segmental sclerosis. RESULTS:
      The cohort consisted of 17 patients, including 10 men and 15 adults. The median
      serum creatinine was 0.9 mg/dl (range=0.7-3.1), median 24-hour urine protein was
      8.0 g/d (3.0-18.0 g), and 14 patients were fully nephrotic, whereas the remaining
      3 patients fulfilled two of three criteria for nephrotic syndrome. Biopsies
      revealed IgA-dominant or codominant deposits accompanied by mesangial
      proliferation in 14 patients (82.4%). Electron microscopy showed mesangial
      deposits and extensive foot process effacement (median=90%). Initial treatment
      consisted of corticosteroids, although many patients required additional agents
      to maintain remission status. Over a median follow-up of 20 months (2.2-82
      months), 14 patients experienced a complete response, and 3 patients showed a
      partial response, with a median response time of 2 months (0.5-27 months). At
      least one relapse of nephrotic syndrome occurred in nine patients (53%). All
      patients exhibited stable or improved renal function over the follow-up period.
      CONCLUSIONS: The findings in this cohort and previous studies suggest that rare
      cases of mild IgA nephropathy with nephrotic range proteinuria exhibit a clinical
      presentation, biopsy findings, treatment response, and outcome more typical of
      IgA nephropathy with superimposed minimal change disease. This study favors the
      view that such cases represent a dual glomerulopathy.

PMID- 24721886
TI  - Novel treatments of autosomal dominant polycystic kidney disease.

PMID- 24721887
TI  - Temporal trajectory of B-type natriuretic peptide in patients with CKD stages 3
      and 4, dialysis, and kidney transplant.
AB  - BACKGROUND AND OBJECTIVES: B-type natriuretic peptide (BNP) concentration
      predicts outcome in patients undergoing dialysis. Because survival and
      cardiovascular risk change across the CKD continuum, serial changes in BNP were
      compared in patients at different CKD stages and after kidney transplantation.
      DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Patients with CKD stages 3 and 4
      (CKD 3-4), dialysis patients, and kidney transplant recipients (KTRs) from one
      center had two measurements of BNP taken a median of 161 days apart in 2003-2004
      and were followed until July 2012. Both BNP-32 (Triage BNP; Biosite Diagnostics)
      and NT-BNP-76 (proBNP; Roche Diagnostics) were assayed. The interaction between
      change in log-transformed BNP concentration over time and patient group was
      tested by fitting regression models on panel data with random effects. Survival
      after the second measurement was compared by tertile of change in BNP. RESULTS:
      Patients with CKD 3-4 (n=48), dialysis patients (n=102), and KTRs (n=73) were
      followed for a median of 5.7, 4.8, and 5.9 years, respectively. The interaction
      between patient group and BNP measurements over time was significant for NT-BNP
      76 (P<0.001) and BNP-32 (P<0.01). Median NT-BNP-76 increased in dialysis patients
      and those with CKD 3-4 from 3850 pg/ml (interquartile range [IQR], 1776-12,323
      pg/ml) to 18,830 pg/ml (IQR, 6114-61,009 pg/ml; P<0.001) and from 698 pg/ml (IQR,
      283-2922 pg/ml) to 2529 pg/ml (IQR, 347-9277 pg/ml; P=0.002), respectively.
      Change was not significant for KTRs or comparisons made with BNP-32. Survival
      rate was significantly lower for patients with the highest tertile of change in
      NT-BNP-76 among patients with CKD 3-4 (P=0.02), but not in the dialysis or KTR
      groups. In 11 patients who received a kidney transplant during the study, median
      NT-BNP-76 decreased from 9607 pg/ml (IQR, 2292-31,282 pg/ml) to 457 pg/ml (IQR,
      203-863 pg/ml) after transplant (P<0.01). CONCLUSIONS: The temporal trajectory of
      BNP differs between dialysis patients and those with CKD 3-4 and KTRs. This has
      important implications for the development of BNP-guided management strategies in
      CKD.

PMID- 24721888
TI  - Low-dose rapamycin (sirolimus) effects in autosomal dominant polycystic kidney
      disease: an open-label randomized controlled pilot study.
AB  - BACKGROUND AND OBJECTIVES: The two largest studies of mammalian target of
      rapamycin inhibitor treatment of autosomal dominant polycystic kidney disease
      (ADPKD) demonstrated no clear benefit on the primary endpoint of total kidney
      volume (TKV) or on eGFR. The present study evaluated two levels of rapamycin on
      the 12-month change in (125)I-iothalamate GFR (iGFR) as the primary endpoint and
      TKV secondarily. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: In a 12-month
      open-label pilot study, 30 adult patients with ADPKD were randomly assigned to
      low-dose (LD) rapamycin (rapamycin trough blood level, 2-5 ng/ml) (LD group,
      n=10), standard-dose (STD) rapamycin trough level (>5-8 ng/ml) (STD group, n=10),
      or standard care (SC group, n=10). They were evaluated with iGFR and noncontrast
      computed tomography. RESULTS: Change in iGFR at 12 months was significantly
      higher in the LD group (7.7+/-12.5 ml/min per 1.73 m(2); n=9) than in the SC
      group (-11.2 +/- 9.1 ml/min per 1.73 m(2); n=9) (LD versus SC: P<0.01). Change in
      iGFR at 12 months in the STD group (1.6 +/- 12.1 ml/min per 1.73 m(2); n=8) was
      not significantly greater than that in the SC group (P=0.07), but it was in the
      combined treatment groups (LD+STD versus SC: P<0.01). Neither eGFR calculated by
      the CKD-Epidemiology Collaboration equation nor TKV (secondary endpoint) changed
      significantly from baseline to 12 months in any of the groups. On the basis of
      results of the mixed model, during the study, patients in the LD group had
      significantly lower trough blood levels of rapamycin (mean range +/- SD, 2.40 +/-
      0.64 to 2.90 +/- 1.20 ng/ml) compared with those in the STD group (3.93 +/- 2.27
      to 5.77 +/- 1.06 ng/ml) (P<0.01). CONCLUSION: Patients with ADPKD receiving LD
      rapamycin demonstrated a significant increase in iGFR compared with those
      receiving standard care, without a significant effect on TKV after 12 months.

PMID- 24721889
TI  - Caregiver burden and hemodialysis.

PMID- 24721890
TI  - Comparison of methylprednisolone plus prednisolone with prednisolone alone as
      initial treatment in adult-onset minimal change disease: a retrospective cohort
      study.
AB  - BACKGROUND AND OBJECTIVES: Previous studies suggested that intravenous
      methylprednisolone possibly accelerates remission of proteinuria in adult-onset
      minimal change disease; its impact on relapse of proteinuria is unknown. DESIGN,
      SETTING, PARTICIPANTS, & MEASUREMENTS: This multicenter retrospective cohort
      study included 125 adult-onset minimal change disease patients diagnosed by
      kidney biopsy between 2000 and 2009 and treated initially with corticosteroid in
      five nephrology centers in Japan participating in the Study of Outcomes and
      Practice Patterns of Minimal Change Disease. Times to first remission and first
      relapse of proteinuria after initiating the first immunosuppressive therapy were
      compared between 65 patients with initial use of intravenous methylprednisolone
      followed by prednisolone and 60 patients with initial use of prednisolone alone
      using multivariate Cox proportional hazards models. After calculating the
      probability of receiving methylprednisolone and prednisolone using a logistic
      regression model (propensity score), the results were ascertained using
      propensity score-matched and -stratified models. RESULTS: During the median 3.6
      years of observation (interquartile range=2.0-6.9), all 65 patients in the
      methylprednisolone and prednisolone group achieved remission within 11 (8-20)
      days of the corticosteroid initiation, whereas in the prednisolone group, 58 of
      60 patients (96.7%) achieved remission within 19 (12-37) days (P<0.001). After
      achieving first remission, 32 (49.2%) patients in the methylprednisolone and
      prednisolone group and 43 (74.1%) patients in the prednisolone group developed at
      least one relapse. Multivariate Cox proportional hazards models revealed that
      methylprednisolone and prednisolone use was significantly associated with early
      remission (multivariate-adjusted hazard ratio, 1.56; 95% confidence interval,
      1.06 to 2.30) and lower incidence of relapse (0.50; 95% confidence interval, 0.29
      to 0.85) compared with prednisolone use alone. These results were ascertained in
      propensity score-based models. No significant difference was observed in
      incidence of adverse events, including infection, aseptic osteonecrosis,
      cataract, diabetes, and gastrointestinal bleeding. CONCLUSIONS: Initial use of
      methylprednisolone was associated with earlier remission and lower incidence of
      relapse in adult-onset minimal change disease patients. Efficacy of
      methylprednisolone should be evaluated in randomized controlled trials.

PMID- 24721891
TI  - Regulation of Potassium Homeostasis.
AB  - Potassium is the most abundant cation in the intracellular fluid, and maintaining
      the proper distribution of potassium across the cell membrane is critical for
      normal cell function. Long-term maintenance of potassium homeostasis is achieved
      by alterations in renal excretion of potassium in response to variations in
      intake. Understanding the mechanism and regulatory influences governing the
      internal distribution and renal clearance of potassium under normal circumstances
      can provide a framework for approaching disorders of potassium commonly
      encountered in clinical practice. This paper reviews key aspects of the normal
      regulation of potassium metabolism and is designed to serve as a readily
      accessible review for the well informed clinician as well as a resource for
      teaching trainees and medical students. 

PMID- 24721892
TI  - Effects of frequent hemodialysis on perceived caregiver burden in the Frequent
      Hemodialysis Network trials.
AB  - BACKGROUND AND OBJECTIVES: Patients receiving hemodialysis often perceive their
      caregivers are overburdened. We hypothesize that increasing hemodialysis
      frequency would result in higher patient perceptions of burden on their unpaid
      caregivers. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: In two separate
      trials, 245 patients were randomized to receive in-center daily hemodialysis (6
      days/week) or conventional hemodialysis (3 days/week) while 87 patients were
      randomized to receive home nocturnal hemodialysis (6 nights/week) or home
      conventional hemodialysis for 12 months. Changes in overall mean scores over time
      in the 10-question Cousineau perceived burden scale were compared. RESULTS: In
      total, 173 of 245 (70%) and 80 of 87 (92%) randomized patients in the Daily and
      Nocturnal Trials, respectively, reported having an unpaid caregiver at baseline
      or during follow-up. Relative to in-center conventional dialysis, the 12-month
      change in mean perceived burden score with in-center daily hemodialysis was -2.1
      (95% confidence interval, -9.4 to +5.3; P=0.58). Relative to home conventional
      dialysis, the 12-month change in mean perceived burden score with home nocturnal
      dialysis was +6.1 (95% confidence interval, -0.8 to +13.1; P=0.08). After
      multiple imputation for missing data in the Nocturnal Trial, the relative
      difference between home nocturnal and home conventional hemodialysis was +9.4
      (95% confidence interval, +0.55 to +18.3; P=0.04). In the Nocturnal Trial,
      changes in perceived burden were inversely correlated with adherence to dialysis
      treatments (Pearson r=-0.35; P=0.02). CONCLUSION: Relative to conventional
      hemodialysis, in-center daily hemodialysis did not result in higher perceptions
      of caregiver burden. There was a trend to higher perceived caregiver burden among
      patients randomized to home nocturnal hemodialysis. These findings may have
      implications for the adoption of and adherence to frequent nocturnal
      hemodialysis.

PMID- 24721894
TI  - Arterial lactate for predicting mortality in children requiring extracorporeal
      membrane oxygenation.
AB  - BACKGROUND: Dynamic arterial lactate indices predict mortality more accurately
      than static arterial lactate measurements in children with septic shock or
      congenital cardiac defects. The current study evaluates whether this also applies
      to children with primary respiratory disease requiring extracorporeal membrane
      oxygenation (ECMO). METHODS: Static arterial lactate levels (LACabs) were
      prospectively collected before and during ECMO support for this single center,
      observational cohort study. Also, time-weighted arterial lactate (LACtw) and
      lactate change over time (LACdelta) were calculated as dynamic indices for,
      respectively, the duration and the trend over time of lactate derangement.
      Intensive care mortality was the primary endpoint. Analyses were performed for
      neonatal and pediatric patients separately. RESULTS: Fifty-six neonatal and 39
      pediatric patients were included. Eighteen (32%) neonatal and 12 (31%) pediatric
      patients died. The evolution of LACabs and LACdelta differed between the
      pediatric survivors and the pediatric non-survivors (P<0.001, P=0.025). The
      hazard ratio was 1.23 (CI95=1.06-1.43, P=0.007) for LACabs and 20.64 (CI95=1.99
      214.20, P=0.011) for LACdelta, indicating that higher lactate levels increase the
      risk for mortality. The predictive value for LACabs was 0.75 (CI95=0.57-0.93) and
      for LACdelta 0.69 (CI95=0.51-0.87), respectively. There were neither consistent
      differences for LACtw in the pediatric patients, nor for any of the static or
      dynamic lactate indices in the neonatal patients. CONCLUSION: Static arterial
      lactate measurements and, to a lesser extent, dynamic arterial lactate indices
      predict mortality in pediatric, but not neonatal ECMO patients. The magnitude and
      trend over time rather than the duration of lactate derangement are associated
      with mortality.

PMID- 24721893
TI  - Effect of pravastatin on total kidney volume, left ventricular mass index, and
      microalbuminuria in pediatric autosomal dominant polycystic kidney disease.
AB  - BACKGROUND AND OBJECTIVES: In autosomal dominant polycystic kidney disease
      (ADPKD), progressive kidney cyst formation commonly leads to ESRD. Because
      important manifestations of ADPKD may be evident in childhood, early intervention
      may have the largest effect on long-term outcome. Statins are known to slow
      progressive nephropathy in animal models of ADPKD. This randomized double-blind
      placebo-controlled phase III clinical trial was conducted from 2007 to 2012 to
      assess the effect of pravastatin on height-corrected total kidney volume (HtTKV)
      and left ventricular mass index (LVMI) by magnetic resonance imaging (MRI) and
      urine microalbumin excretion (UAE) in children and young adults with ADPKD.
      DESIGNS, SETTING, PARTICIPANTS, & MEASUREMENTS: There were 110 pediatric
      participants with ADPKD and normal kidney function receiving lisinopril who were
      randomized to treatment with pravastatin or placebo for a 3-year period with
      evaluation at 0, 18, and 36 months. The primary outcome variable was a >= 20%
      change in HtTKV, LVMI, or UAE over the study period. RESULTS: Ninety-one
      participants completed the 3-year study (83%). Fewer participants receiving
      pravastatin achieved the primary endpoint compared with participants receiving
      placebo (69% versus 88%; P=0.03). This was due primarily to a lower proportion
      reaching the increase in HtTKV (46% versus 68%; P=0.03), with similar findings
      observed between study groups for LVMI (25% versus 38%; P=0.18) and UAE (47%
      versus 39%; P=0.50). The percent change in HtTKV adjusted for age, sex, and
      hypertension status over the 3-year period was significantly decreased with
      pravastatin (23% +/- 3% versus 31% +/- 3%; P=0.02). CONCLUSIONS: Pravastatin is
      an effective agent to slow progression of structural kidney disease in children
      and young adults with ADPKD. These findings support a role for early intervention
      with pravastatin in this condition.

PMID- 24721895
TI  - Use of cisatracurium in critical care: a review of the literature.
AB  - Cisatracurium is currently one of the most commonly used neuromuscular blocking
      agent (NMBA) in intensive care units. Cisatracurium was developed primarily for
      anaesthetic purposes in order to attempt to resolve some of the problems
      associated with earlier NMBAs, such as histamine release and laudanosine
      accumulation. Cisatracurium, the the R-cis-R-cis isomer of atracurium, is up to 5
      times more potent than atracurium and so is administered in smaller quantities
      and produces a lesser degree of laudanosine accumulation in the plasma. In both
      adult and paediatric settings cisatracurium has favourable pharmacological
      characteristics compared to vecuronium, a steroid based NMBA often used in
      critical care. Recent randomised clinical trials suggested that the use of
      cisatracurium is associated with better outcome in acute respiratory distress
      syndrome (ARDS). Its use has been associated with better outcomes in therapeutic
      hypothermia and in traumatic brain injury. Although it has many favorable
      pharmacological properties, it is more expensive than comparable agents and some
      safety concerns persist regarding adverse events associated with the drug. The
      aim of the present study was to perform the first comprehensive review to date of
      all literature relating to the use of cisatracurium in critically ill patients. 

PMID- 24721896
TI  - Globalization and economic growth: empirical evidence on the role of
      complementarities.
AB  - This study was carried out to investigate the effect of economic globalization on
      economic growth in OIC countries. Furthermore, the study examined the effect of
      complementary policies on the growth effect of globalization. It also
      investigated whether the growth effect of globalization depends on the income
      level of countries. Utilizing the generalized method of moments (GMM) estimator
      within the framework of a dynamic panel data approach, we provide evidence which
      suggests that economic globalization has statistically significant impact on
      economic growth in OIC countries. The results indicate that this positive effect
      is increased in the countries with better-educated workers and well-developed
      financial systems. Our finding shows that the effect of economic globalization
      also depends on the country's level of income. High and middle-income countries
      benefit from globalization whereas low-income countries do not gain from it. In
      fact, the countries should receive the appropriate income level to be benefited
      from globalization. Economic globalization not only directly promotes growth but
      also indirectly does so via complementary reforms. 

PMID- 24721897
TI  - The influence of hydrodynamic diameter and core composition on the magnetoviscous
      effect of biocompatible ferrofluids.
AB  - Suspensions of magnetic nanoparticles have received increasing interest in the
      biomedical field. While these ferrofluids are already used for magnetic resonance
      imaging, emerging research on cancer treatment focuses, for example, on employing
      the particles as drug carriers, or using them in magnetic hyperthermia to destroy
      diseased cells by heating of the particles. To enable safe and effective
      applications, an understanding of the flow behaviour of the ferrofluids is
      essential. Regarding the applications mentioned above, in which flow phenomena
      play an important role, viscosity under the influence of an external magnetic
      field is of special interest. In this respect, the magnetoviscous effect (MVE)
      leading to an increasing viscosity if an external magnetic field of a certain
      strength is applied, is well-known for singlecore ferrofluids used in the
      engineering context. In the biomedical context, multicore ferrofluids are
      preferred in order to avoid remanence magnetization and to enable a deposition of
      the particles by the organism without complications. This study focuses on a
      comparison of the MVE for three ferrofluids whose composition is identical except
      in relation to their hydrodynamic diameter and core composition-one of the fluids
      contains singlecore particles, while the other two feature multicore particles.
      This enables confident conclusions about the influence of those parameters on
      flow behaviour under the influence of a magnetic field. The strong effects found
      for two of the fluids should be taken into account, both in future investigations
      and in the potential use of such ferrofluids, as well as in manufacturing, in
      relation to the optimization of flow behaviour. 

PMID- 24721899
TI  - Immunology Letters. IMmune-related Pathologies: Understanding Leukocyte Signaling
      and Emerging Therapies--IMPULSE 2013. Introduction.

PMID- 24721898
TI  - Enzyme-free passage of human pluripotent stem cells by controlling divalent
      cations.
AB  - Enzymes used for passaging human pluripotent stem cells (hPSCs) digest cell
      surface proteins, resulting in cell damage. Moreover, cell dissociation using
      divalent cation-free solutions causes apoptosis. Here we report that Mg(2+) and
      Ca(2+) control cell-fibronectin and cell-cell binding of hPSCs, respectively,
      under feeder- and serum-free culture conditions without enzyme. The hPSCs were
      detached from fibronectin-, vitronectin- or laminin-coated dishes in low
      concentrations of Mg(2+) and remained as large colonies in high concentrations of
      Ca(2+). Using enzyme-free solutions containing Ca(2+) without Mg(2+), we
      successfully passaged hPSCs as large cell clumps that showed less damage than
      cells passaged using a divalent cation-free solution or dispase. Under the same
      conditions, the undifferentiated and early-differentiated cells could also be
      harvested as a cell sheet without being split off. Our enzyme-free passage of
      hPSCs under a serum- and feeder-free culture condition reduces cell damage and
      facilitates easier and safer cultures of hPSCs. 

PMID- 24721900
TI  - Are high energy proton beams ideal for AB-BNCT? A brief discussion from the
      viewpoint of fast neutron contamination control.
AB  - High energy proton beam (>8MeV) is favorable for producing neutrons with high
      yield. However, the produced neutrons are of high energies. These high energy
      neutrons can cause severe fast neutron contamination and degrade the BNCT
      treatment quality if they are not appropriately moderated. Hence, this study aims
      to briefly discuss the issue, from the viewpoint of fast neutron contamination
      control, whether high energy proton beam is ideal for AB-BNCT or not. In this
      study, D2O, PbF4, CaF2, and Fluental(TM) were used standalone as moderator
      materials to slow down 1-, 6-, and 10-MeV parallelly incident neutrons. From the
      calculated results, we concluded that neutrons produced by high energy proton
      beam could not be easily moderated by a single moderator to an acceptable
      contamination level and still with reasonable epithermal neutron beam intensity.
      Hence, much more complicated and sophisticated designs of beam shaping assembly
      have to be developed when using high energy proton beams. 

PMID- 24721901
TI  - Duplication at Xq28 involving IKBKG is associated with progressive macrocephaly,
      recurrent infections, ectodermal dysplasia, benign tumors, and neuropathy.
AB  - Duplications on Xq28 are common, although quite variable in size, but usually
      include the MECP2 gene. Here, we present a patient with a unique, small, 167-kb
      duplication at Xq28, not including MECP2. The most important gene in the
      duplicated region was IKBKG, mutations in which can cause a variety of distinct
      syndromes. Our patient's symptoms overlapped with different IKBKG-associated
      phenotypes, including hypohidrotic ectodermal dysplasia, incontinentia pigmenti,
      immunodeficiency, recurrent isolated invasive pneumococcal disease and anhidrotic
      ectodermal dysplasia with immunodeficiency, osteopetrosis, and lymphedema. In
      addition, she also had peripheral neuropathy, gastroparesis and various benign
      tumors, but no intellectual disability. Mixed syndromal presentation in several
      patients with IKBKG defect implies that IKBKG-related phenotypes are more like a
      spectrum, rather than distinct syndromes. We also suggest our patient's
      multisystem phenotype to be a novel contiguous gene syndrome, in which the key
      features include immune deficiency, macrocephaly, skin abnormalities,
      gastroparesis, peripheral small-fiber neuropathy, and benign tumors. 

PMID- 24721902
TI  - A blunted anxiolytic like effect of curcumin against acute lead induced anxiety
      in rat: involvement of serotonin.
AB  - Anxiety is one of the most common mental disorders sharing extreme or
      pathological anxiety states as the primary disturbance in mood or emotional tone,
      with increased fear and exaggerated acute stress responses. Medicinal plants are
      very variable, but some of them are used as a spice such as curcumin (Curcuma
      longa). Curcumin shows a wide range of pharmacological potentialities, however,
      little is known about its anxiolytic properties. The aim of our study was to
      assess the anti-anxiety potential of curcumin extract against experimental lead
      induced-anxiety in rats. Experiments were carried out on male Wistar rats
      intoxicated acutely with an intraperitoneal injection of Pb (25mg/kg B.W.) and/or
      concomitantly with administration of curcumin (30 mg/kg B.W.) for 3 days. Using
      immunohistochemistry and anxiety assessment tests (dark light box and elevated
      plus maze), we evaluated, respectively, the expression of serotonin (5HT) in the
      dorsal raphe nucleus (DRN) and the anxiety state in our animals. Our results
      showed, for the first time, a noticeable anxiolytic effect of curcumin against
      lead induced anxiety in rats and this may possibly result from modulation of
      central neuronal monoaminergic neurotransmission, especially serotonin, which has
      shown a significant reduction of the immunoreactivity within the DRN.

PMID- 24721903
TI  - Effects of HDV infection and pegylated interferon alpha treatment on the natural
      killer cell compartment in chronically infected individuals.
AB  - OBJECTIVE: Although hepatitis delta is considered an immune-mediated disease,
      adaptive immune responses to hepatitis delta virus (HDV) are hardly detectable.
      Thus, the role of other immune responses, including those mediated by natural
      killer (NK) cells, must be considered in HDV pathogenesis and in treatments with
      immune-stimulating agents such as interferon (IFN)alpha. However, the phenotype
      and function of NK cells in chronic HDV infection, or in HDV-infected individuals
      undergoing IFNalpha treatment, have not been extensively studied. DESIGN: We
      performed an extensive analysis of NK cells in chronically HDV-infected patients
      before and during treatment with IFNalpha, and compared the results with those
      for patients with HBV mono-infection as well as healthy controls. RESULTS: In
      untreated HDV-infected patients, a higher than normal frequency of NK cells was
      observed in peripheral blood with unaltered phenotypic NK cell differentiation
      status. In contrast, long-term IFNalpha treatment of HDV-infected patients caused
      a significant change in NK cell differentiation status, with selective loss of
      terminally differentiated NK cells and, in parallel, a relative enrichment in
      immature NK cell subsets. Treatment was associated with marked functional
      impairment of the NK cells, which was independent of the changes in NK cell
      differentiation status. Furthermore, treatment polarised NK cell IFN signalling
      from STAT4 towards STAT1 dependency. Strikingly, a high frequency of CD56(dim) NK
      cells at baseline was positively associated with IFNalpha treatment outcome in
      the patients. CONCLUSIONS: We describe in detail how HDV infection, and IFNalpha
      treatment of this infection, affects the NK cell compartment and what
      consequences this has for the functional capacity of NK cells.

PMID- 24721905
TI  - Morphea as a sign of autoimmune syndrome induced by adjuvants (ASIA).

PMID- 24721904
TI  - The combination of autofluorescence endoscopy and molecular biomarkers is a novel
      diagnostic tool for dysplasia in Barrett's oesophagus.
AB  - OBJECTIVE: Endoscopic surveillance for Barrett's oesophagus (BO) is limited by
      sampling error and the subjectivity of diagnosing dysplasia. We aimed to compare
      a biomarker panel on minimal biopsies directed by autofluorescence imaging (AFI)
      with the standard surveillance protocol to derive an objective tool for dysplasia
      assessment. DESIGN: We performed a cross-sectional prospective study in three
      tertiary referral centres. Patients with BO underwent high-resolution endoscopy
      followed by AFI-targeted biopsies. 157 patients completed the biopsy protocol.
      Aneuploidy/tetraploidy; 9p and 17p loss of heterozygosity; RUNX3, HPP1 and p16
      methylation; p53 and cyclin A immunohistochemistry were assessed. Bootstrap
      resampling was used to select the best diagnostic biomarker panel for high-grade
      dysplasia (HGD) and early cancer (EC). This panel was validated in an independent
      cohort of 46 patients. RESULTS: Aneuploidy, p53 immunohistochemistry and cyclin A
      had the strongest association with dysplasia in the per-biopsy analysis and, as a
      panel, had an area under the receiver operating characteristic curve of 0.97 (95%
      CI 0.95 to 0.99) for diagnosing HGD/EC. The diagnostic accuracy for HGD/EC of the
      three-biomarker panel from AFI+ areas was superior to AFI- areas (p<0.001).
      Compared with the standard protocol, this panel had equal sensitivity for HGD/EC,
      with a 4.5-fold reduction in the number of biopsies. In an independent cohort of
      patients, the panel had a sensitivity and specificity for HGD/EC of 100% and 85%,
      respectively. CONCLUSIONS: A three-biomarker panel on a small number of AFI
      targeted biopsies provides an accurate and objective diagnosis of dysplasia in
      BO. The clinical implications have to be studied further.

PMID- 24721907
TI  - Generalized eruptive xanthomas associated with diabetic dyslipidemia.

PMID- 24721906
TI  - Chromatin landscapes of retroviral and transposon integration profiles.
AB  - The ability of retroviruses and transposons to insert their genetic material into
      host DNA makes them widely used tools in molecular biology, cancer research and
      gene therapy. However, these systems have biases that may strongly affect
      research outcomes. To address this issue, we generated very large datasets
      consisting of ~ 120,000 to ~ 180,000 unselected integrations in the mouse genome
      for the Sleeping Beauty (SB) and piggyBac (PB) transposons, and the Mouse Mammary
      Tumor Virus (MMTV). We analyzed ~ 80 (epi)genomic features to generate bias maps
      at both local and genome-wide scales. MMTV showed a remarkably uniform
      distribution of integrations across the genome. More distinct preferences were
      observed for the two transposons, with PB showing remarkable resemblance to bias
      profiles of the Murine Leukemia Virus. Furthermore, we present a model where
      target site selection is directed at multiple scales. At a large scale, target
      site selection is similar across systems, and defined by domain-oriented
      features, namely expression of proximal genes, proximity to CpG islands and to
      genic features, chromatin compaction and replication timing. Notable differences
      between the systems are mainly observed at smaller scales, and are directed by a
      diverse range of features. To study the effect of these biases on integration
      sites occupied under selective pressure, we turned to insertional mutagenesis
      (IM) screens. In IM screens, putative cancer genes are identified by finding
      frequently targeted genomic regions, or Common Integration Sites (CISs). Within
      three recently completed IM screens, we identified 7%-33% putative false positive
      CISs, which are likely not the result of the oncogenic selection process.
      Moreover, results indicate that PB, compared to SB, is more suited to tag
      oncogenes.

PMID- 24721908
TI  - Can equids be a reservoir of Leishmania braziliensis in endemic areas?
AB  - In this study, we detected Leishmania (Viannia) braziliensis infection in equids
      living in endemic regions of cutaneous leishmaniasis. To determine the role of
      these animals in the Leishmania cycle, we used two approaches: serological and
      molecular methods. Antibodies to the parasite were assayed using the Enzyme
      Linked Immunosorbent Assay (ELISA). Blood samples were collected and tested by
      polymerase chain reaction (PCR), and the positive products were sequenced. The
      results showed that 11.0% (25/227) of the equids were seropositive for Leishmania
      sp, and 16.3% (37/227) were PCR positive. Antibodies were detected in 20 horses,
      3 donkeys, and 2 mules, and the parasite DNA was detected in 30 horses, 5
      donkeys, and 2 mules. Sequencing the amplified DNA revealed 100% similarity with
      sequences for Viannia complex, corroborating the results of PCR for L.
      braziliensis. Our results show that equids are infected with L. braziliensis,
      which could be food sources for phlebotomines in the peridomiciliary environment
      and consequently play a role in the cutaneous leishmaniasis cycle. 

PMID- 24721910
TI  - Correction: Robust metrics for assessing the performance of different verbal
      autopsy cause assignment methods in validation studies.

PMID- 24721909
TI  - Novel skin phenotypes revealed by a genome-wide mouse reverse genetic screen.
AB  - Permanent stop-and-shop large-scale mouse mutant resources provide an excellent
      platform to decipher tissue phenogenomics. Here we analyse skin from 538 knockout
      mouse mutants generated by the Sanger Institute Mouse Genetics Project. We
      optimize immunolabelling of tail epidermal wholemounts to allow systematic
      annotation of hair follicle, sebaceous gland and interfollicular epidermal
      abnormalities using ontology terms from the Mammalian Phenotype Ontology. Of the
      50 mutants with an epidermal phenotype, 9 map to human genetic conditions with
      skin abnormalities. Some mutant genes are expressed in the skin, whereas others
      are not, indicating systemic effects. One phenotype is affected by diet and
      several are incompletely penetrant. In-depth analysis of three mutants, Krt76,
      Myo5a (a model of human Griscelli syndrome) and Mysm1, provides validation of the
      screen. Our study is the first large-scale genome-wide tissue phenotype screen
      from the International Knockout Mouse Consortium and provides an open access
      resource for the scientific community. 

PMID- 24721927
TI  - The atomic-scale mechanism for the enhanced glass-forming-ability of a Cu-Zr
      based bulk metallic glass with minor element additions.
AB  - It is known that the glass forming-ability (GFA) of bulk metallic glasses (BMGs)
      can be greatly enhanced via minor element additions. However, direct evidence has
      been lacking to reveal its structural origin despite different theories hitherto
      proposed. Through the high-resolution transmission-electron-microscopy (HRTEM)
      analysis, here we show that the content of local crystal-like orders increases
      significantly in a Cu-Zr-Al BMG after a 2-at% Y addition. Contrasting the
      previous studies, our current results indicate that the formation of crystal-like
      order at the atomic scale plays an important role in enhancing the GFA of the Cu
      Zr-Al base BMG. 

PMID- 24721928
TI  - RhoGDI2 promotes epithelial-mesenchymal transition via induction of Snail in
      gastric cancer cells.
AB  - Rho GDP dissociation inhibitor 2 (RhoGDI2) expression correlates with tumor
      growth, metastasis, and chemoresistance in gastric cancer. Here, we show that
      RhoGDI2 functions in the epithelial-mesenchymal transition (EMT), which is
      responsible for invasiveness during tumor progression. This tumorigenic activity
      is associated with repression of E-cadherin by RhoGDI2 via upregulation of Snail.
      Overexpression of RhoGDI2 induced phenotypic changes consistent with EMT in
      gastric cancer cells, including abnormal epithelial cell morphology, fibroblast
      like properties, and reduced intercellular adhesion. RhoGDI2 overexpression also
      resulted in decreased expression of the epithelial markers E-cadherin and beta
      catenin and increased expression of the mesenchymal markers vimentin and
      fibronectin. Importantly, RhoGDI2 overexpression also stimulated the expression
      of Snail, a repressor of E-cadherin and inducer of EMT, but not other family
      members such as Slug or Twist. RNA interference-mediated knockdown of Snail
      expression suppressed RhoGDI2-induced EMT and invasion, confirming that the
      effect was Snail-specific. These results indicate that RhoGDI2 plays a critical
      role in tumor progression in gastric cancer through induction of EMT. Targeting
      RhoGDI2 may thus be a useful strategy to inhibit gastric cancer cell invasion and
      metastasis. 

PMID- 24721930
TI  - Carotid-femoral pulse wave velocity in the elderly.
AB  - Predictive value of arterial stiffness in cardiovascular disease has been
      recognized for many decades. Carotid-femoral pulse wave velocity (cfPWV), as a
      noninvasive measurement, has been recommended as a gold standard of arterial
      stiffness, and we believe that this surrogate of arterial stiffness has been
      refined to the point that its utility in routine clinical practice need to be
      recommended. Considering the worldwide aging population and aging itself as a
      major cause of arterial stiffness, we would focus in this article, from a
      practical point of view, on cfPWV in the elderly, and review the current
      knowledge on the effect of arterial aging on cfPWV measurements, as well as the
      significance of its clinical application in the elderly. 

PMID- 24721929
TI  - Modulation of blood pressure response to exercise by physical activity and
      relationship with resting blood pressure during pregnancy.
AB  - OBJECTIVE: To determine whether physical activity and blood pressure (BP)
      response to exercise in early pregnancy are related to resting BP at the end of
      pregnancy. Understanding physiological BP responses to exercise during pregnancy
      will help in improving BP profile and guiding exercise recommendations in
      pregnant women. METHODS: Maternal physical activity, cardiorespiratory fitness
      (VO2peak) and BP (systolic and diastolic) at rest and during exercise (submaximal
      and relative response) were assessed at 16 weeks of gestation in 61 normotensive
      pregnant women. BP at 36 weeks of gestation and obstetrical outcomes were
      collected from maternal charts. RESULTS: Related to resting DBP at 16 weeks (r = 
      -0.28, P = 0.028), total energy expenditure spend at any physical activity in
      early pregnancy was also associated with resting SBP at 36 weeks (r =  -0.27, P =
      0.038). On the contrary, although related to VO2peak (r =  -0.57, P < 0.0001) and
      energy expenditure spent at sports and exercise (r =  -0.29, P = 0.024), the
      relative SBP response to exercise at 16 weeks was not associated with resting BP
      at 36 weeks. Strongly associated with resting BP at 16 weeks and also with total
      energy expenditure, submaximal BP response to exercise at 16 weeks was related to
      resting SBP and DBP at 36 weeks (r = 0.41, P = 0.001 and r = 0.26, P = 0.051,
      respectively). CONCLUSION: In normotensive women, physical activity performed in
      early pregnancy appears to slightly modulate resting BP in early and late
      pregnancy. However, further investigations are needed to determine which physical
      activity-related parameter in response to exercise best predicts BP variations
      during pregnancy.

PMID- 24721931
TI  - Prevalence, awareness, treatment and control of hypertension in urban poor
      communities in Accra, Ghana.
AB  - BACKGROUND: Hypertension is a major public health problem in many sub-Saharan
      African countries including Ghana, but data on urban poor communities are
      limited. The aim of this study was therefore to assess the prevalence, awareness,
      management and control of hypertension among a young adult population in their
      reproductive ages living in urban poor communities in Accra. METHODS: Cross
      sectional, population-based survey of 714 young adults in their reproductive ages
      (women aged 15-49 years, men aged 15-59 years) living in three urban poor suburbs
      of Accra, Ghana. RESULTS: The overall prevalence of hypertension in all three
      communities was 28.3% (women 25.6% and men 31.0%). Among respondents who had
      hypertension, 7.4% were aware of their condition; 4% were on antihypertensive
      medication while only 3.5% of hypertensive individuals had adequate blood
      pressure (BP) control (BP <140/90  mmHg). The level of awareness and treatment
      was lower in men than in women (3.1 and 1.3% for men and 11.9 and 6.5% for women,
      respectively). Among individuals with hypertension, the rate of control was
      higher among women than among men (5.0 and 2.1%, respectively). CONCLUSION:
      Although about a quarter of the young adult population in these low-income
      communities of Accra have hypertension, the levels of awareness, treatment and
      control are abysmally low. We recommend community-specific primary and secondary
      prevention interventions that draw on existing resources, specifically
      implementing cardiovascular disease (CVD) interventions in faith-based
      organizations and task-shifting CVD care through the national Community-based
      Health Planning and Services (CHPS) programme.

PMID- 24721932
TI  - Transovarial transmission of Orientia tsutsugamushi in Leptotrombidium palpale
      (Acari: Trombiculidae).
AB  - Transovarial transmission of Orientia tsutsugamushi in colonies of
      Leptotrombidium palpale was studied in the parent and F1 and F2 generations. Both
      transovarial transmission and filial infection rates were 100% in the parent and
      F1 generations of Leptotrombidium palpale. The filial infection rate in the F1
      generation was 100%, but it declined to 94.3% in the F2 progeny. The sex ratio of
      the F1 generation from infected L. palpale was 1?0.8 (male:female) and the
      proportion of males was relatively high. This study is the first to report on the
      transovarial transmission of O. tsutsugamushi in L. palpale. High transovarial
      transmission rates in L. palpale suggest that this species might be one of the
      major vectors of tsutsugamushi disease in Korea. 

PMID- 24721933
TI  - A 5000-fold increase in the specificity of a bacterial phosphotriesterase for
      malathion through combinatorial active site mutagenesis.
AB  - Phosphotriesterases (PTEs) have been isolated from a range of bacterial species,
      including Agrobcaterium radiobacter (PTEAr), and are efficient enzymes with broad
      substrate ranges. The turnover rate of PTEAr for the common organophosphorous
      insecticide malathion is lower than expected based on its physical properties;
      principally the pka of its leaving group. In this study, we rationalise the
      turnover rate of PTEAr for malathion using computational docking of the substrate
      into a high resolution crystal structure of the enzyme, suggesting that malathion
      is too large for the PTEAr binding pocket. Protein engineering through
      combinatorial active site saturation testing (CASTing) was then used to increase
      the rate of malathion turnover. Variants from a CASTing library in which Ser308
      and Tyr309 were mutated yielded variants with increased activity towards
      malathion. The most active PTEAr variant carried Ser308Leu and Tyr309Ala
      substitutions, which resulted in a ca. 5000-fold increase in kcat/KM for
      malathion. X-ray crystal structures for the PTEAr Ser308Leu?Tyr309Ala variant
      demonstrate that the access to the binding pocket was enhanced by the replacement
      of the bulky Tyr309 residue with the smaller alanine residue. 

PMID- 24721935
TI  - Trapping of drops by wetting defects.
AB  - Controlling the motion of drops on solid surfaces is crucial in many natural
      phenomena and technological processes including the collection and removal of
      rain drops, cleaning technology and heat exchangers. Topographic and chemical
      heterogeneities on solid surfaces give rise to pinning forces that can capture
      and steer drops in desired directions. Here we determine general physical
      conditions required for capturing sliding drops on an inclined plane that is
      equipped with electrically tunable wetting defects. By mapping the drop dynamics
      on the one-dimensional motion of a point mass, we demonstrate that the trapping
      process is controlled by two dimensionless parameters, the trapping strength
      measured in units of the driving force and the ratio between a viscous and an
      inertial time scale. Complementary experiments involving superhydrophobic
      surfaces with wetting defects demonstrate the general applicability of the
      concept. Moreover, we show that electrically tunable defects can be used to guide
      sliding drops along actively switchable tracks-with potential applications in
      microfluidics. 

PMID- 24721936
TI  - Current status of robotic and laparoscopic techniques in radical cystectomy and
      diversion procedures for bladder cancer: review.
AB  - Across the world there has been an increased interest in minimally invasive
      approaches in extirpative and reconstructive surgery for bladder cancer.
      Minimally invasive approaches i.e. robotic and pure laparoscopic radical
      cystectomy have the greatest advantage of reduced blood loss, postoperative pain,
      quicker recovery of bowel function and earlier convalescence. Compared to
      established open techniques, there have been increasing reports of equivalent
      oncologic out comes and reduced complication rates in short and intermediate
      follow-ups. There have been several reports on urinary diversions achieved
      through minimal invasion and there is increasing interest to perform with robotic
      assistance. This review aims to review the currently published literature,
      technical aspects of the procedure, perioperative, oncologic and functional
      outcomes. 

PMID- 24721934
TI  - Comparative population genomics of the Borrelia burgdorferi species complex
      reveals high degree of genetic isolation among species and underscores benefits
      and constraints to studying intra-specific epidemiological processes.
AB  - Lyme borreliosis, one of the most frequently contracted zoonotic diseases in the
      Northern Hemisphere, is caused by bacteria belonging to different genetic groups
      within the Borrelia burgdorferi species complex, which are transmitted by ticks
      among various wildlife reservoirs, such as small mammals and birds. These
      features make the Borrelia burgdorferi species complex an attractive biological
      model that can be used to study the diversification and the epidemiology of
      endemic bacterial pathogens. We investigated the potential of population genomic
      approaches to study these processes. Sixty-three strains belonging to three
      species within the Borrelia burgdorferi complex were isolated from questing ticks
      in Alsace (France), a region where Lyme disease is highly endemic. We first aimed
      to characterize the degree of genetic isolation among the species sampled.
      Phylogenetic and coalescent-based analyses revealed clear delineations: there was
      a ~50 fold difference between intra-specific and inter-specific recombination
      rates. We then investigated whether the population genomic data contained
      information of epidemiological relevance. In phylogenies inferred using most of
      the genome, conspecific strains did not cluster in clades. These results raise
      questions about the relevance of different strategies when investigating pathogen
      epidemiology. For instance, here, both classical analytic approaches and
      phylodynamic simulations suggested that population sizes and migration rates were
      higher in B. garinii populations, which are normally associated with birds, than
      in B. burgdorferi s.s. populations. The phylogenetic analyses of the infection
      related ospC gene and its flanking region provided additional support for this
      finding. Traces of recombination among the B. burgdorferi s.s. lineages and
      lineages associated with small mammals were found, suggesting that they shared
      the same hosts. Altogether, these results provide baseline evidence that can be
      used to formulate hypotheses regarding the host range of B. burgdorferi lineages
      based on population genomic data. 

PMID- 24721937
TI  - Robot-assisted renal surgery: current indications and results.
AB  - Robotic technology is the natural evolution and simplification of traditional
      laparoscopy. Robotic surgery has the same benefits of traditional laparoscopic
      surgery in terms of cosmetic results, pain control and short in-hospital stay.
      However, magnified three-dimensional vision and the use of fully articulated
      wristed-instruments allow to increase the precision control. Recently, robotic
      surgery has been even more used in urology. In fact, robot-assisted radical
      prostatectomy (RARP) is currently the most common treatment used for localized
      prostate cancer in the United States. Perioperative and functional outcomes
      resulted significantly better after RARP. As a consequence of the diffusion of
      RARP, other urological procedures were performed using the robotic approach.
      Particular attention has been paid to the use of robotic surgery for the
      treatment of benign and malignant renal diseases. In 2002 the first robot
      assisted pyeloplasty was performed followed by the first robot-assisted partial
      nephrectomy. This last procedure had widespread a lot in the last years and it
      can currently be considered as the main alternative to the traditional open
      partial nephrectomy. Finally, the evolution of technology and surgeon skills
      allowed us to consider the less invasive approaches also for renal
      transplantation surgery and vena cava tumor thrombectomy. The objective of this
      review was to analyze current indications and outcomes of robot-assisted
      procedures for the treatment of benign and malignant renal diseases. 

PMID- 24721938
TI  - Laparoendoscopic single-site surgery, minilaparoscopy and natural orifice
      transluminal endoscopic surgery in urology.
AB  - This article reviews the development of laparo-endoscopic single-site surgery
      (LESS), minilaparoscopy (MiniLap), and natural orifice transluminal endoscopic
      surgery (NOTES) with a particular focus on the applications in urologic surgery.
      We also provide the reader with a focused summary of the relevant nomenclature,
      history, and comparative outcomes. A literature search was conducted on LESS,
      MiniLap, needlescopy, microlaparoscopy and NOTES procedures in urology which is
      current through January 2013. The most relevant contemporary publications were
      selected and the pertinent findings were reviewed. Over the last few decades, we
      note that many innovative surgeons have performed a myriad of urologic procedures
      using LESS, MiniLap and NOTES techniques. These techniques are beginning to
      garner interest throughout the world; however, the enthusiasm for said
      techniques, while high, has not yet been met with high level scientific data
      clearly demonstrating the advantages of these approaches over conventional
      laparoscopy. In this review, we outline the history and clinical implementation
      of these techniques while also reviewing the comparative data where it exists. We
      attempt to provide the reader with a balanced overview of these techniques, their
      origins and lay the groundwork for future research and development. 

PMID- 24721939
TI  - Diagnosis and management of upper tract urothelial carcinoma.
AB  - Urothelial carcinoma of the upper urinary tract (UTUC) is a rare disease,
      comprising only 5-10% of all urothelial malignancies. There is a paucity of high
      level evidence to guide treatment decisions due to the rarity of the disease.
      Through the creation of multi-institutional collaborations in recent years, our
      understanding of the natural history of UTUC and treatment algorithms has
      improved. However, our understanding of UTUC is mostly driven by extrapolation of
      findings and paradigms of urothelial carcinoma of the urinary bladder. With
      current imaging techniques and biopsy modalities, accurate diagnosis and staging
      remains difficult for this disease and prognostic models are limited in their
      ability to predict clinical outcomes. As such, over or under-treatment is common,
      highlighting the need for individualized treatment regimens which often require a
      multimodal approach. Endoscopic or radical resection represent the mainstays of
      treatment, while the role of intraluminal agents and systemic chemotherapy is yet
      to be clearly defined. Herein we review current concepts and management
      strategies as well as recent developments in UTUC. 

PMID- 24721940
TI  - Surgical management of locally advanced and metastatic renal cancer: neoadjuvant
      and adjuvant strategies.
AB  - Surgery remains the treatment of choice for locally advanced or metastatic renal
      cell carcinoma. However, the contribution of targeted therapies has recently
      significantly impacted recurrence-free survival in metastatic patients,
      challenging in some cases the real interest of nephrectomy. Waiting for the
      results of CARMENA trial, assessing the impact of cytoreductive nephrectomy on
      survival, neoadjuvant and adjuvant strategies are emerging. In locally advanced
      disease, adjuvant therapy should be considered if the patient is considered at
      high risk of progression, and therefore require its inclusion in a prospective
      randomized trial. Neo-adjuvant anti-angiogenic strategies show a quite modest
      improvement in resectability of primary tumor, while allowing performing
      translational research. However, many questions remain on hold in terms of
      precise indications, choice of drugs, toxicity and optimal dosing schedule. All
      these questions explain the current development of phase III trials. 

PMID- 24721941
TI  - Urological tumors in renal transplantation.
AB  - The aim of this paper was to review the risk and incidence of urological
      malignancies and the clinical characteristics and outcomes of renal transplant
      urological malignancies. Medline/PubMed from January 1980 to February 2013 was
      searched to identify all medical literature about native kidney, graft bladder
      and prostate cancers. Comparing to general population, risk of kidney cancer was
      found to be 7 to 10 times greater and most of them are incidental low-stage, low
      grade tumors with a good prognosis. Open and laparoscopic radical nephrectomies
      without lymph nodes dissection were reported to be safe. Incidence of graft RCC
      was 0.19%. Papillary carcinomas represented more than 50% of de novo graft
      carcinomas, which seemed to be low-grade carcinomas with good prognosis. Risk of
      prostate cancer was two times higher. Open or laparoscopic radical prostatectomy
      is safe and feasible for management of localized prostate cancer in patients with
      kidney allograft. Upper urinary tract (UUT) transitional cell carcinoma (TCC)
      incidence was reported between 0.7% and 3.8%. Reports suggested a 3-fold
      increased risk of developing bladder TCC. Intravesical BCG in superficial bladder
      cancer and/or CIS is a valid option. For invasive urothelial tumor, radical
      cystectomy in renal transplant patients remains the best treatment. Oncological
      outcomes of urological cancers in renal transplant recipients are good and
      conservative treatment should be preferred each time it is feasible to prevent
      returning to dialysis following recommendations of urological cancer treatment.
      Close monitoring of renal transplant recipient must be performed with at least an
      abdominopelvic US and PSA measurement once a year. 

PMID- 24721942
TI  - Prescription of oral antidiabetic drugs in K/DIGO chronic kidney disease stage 3
      and 4: a single centre report.
AB  - AIM: Evaluation of chronic kidney disease (CKD) is essential in order to
      prescribe properly oral antidiabetic drugs (OADs). The aim of our study was to
      report hypoglycemic drugs prescription to CKD in a cohort of type 2 diabetes
      mellitus (DM) outpatients. METHODS: This survey included 1686 outpatients with
      type 2 DM treated with OADs who were not taking insulin evaluated by a team of
      diabetologists. Glomerular filtration rate (GFR) was calculated by the CKD-EPI
      formula and subjects were classified in the K/DIGO stages. Main clinical
      parameters were also evaluated. RESULTS: Patients were aged 68+/-10 years, 57.1%
      were males, Body Mass Index was 30+/-5 kg/m2, glycated hemoglobin 8+/-1%,
      systolic and diastolic blood pressure values were 138+/-15/80+/-9 mmHg. Serum
      creatinine was 1.03+/-0.35 mg/dL and GFR 71+/-21 mL/min/1.73 m2. In 504 patients
      (30%) GFR was lower than 60 mL/min/1.73 m2. The different treatment groups had
      different GFR and hypoglycaemic drugs were prescribed differently in the
      different K/DIGO stages. The majority of subjects in stage 3A and 3B were treated
      with repaglinide, however a significant percentage of them were treated with
      metformin and sulfonylureas. Nearly half of subjects with CKD stage 4 were
      treated with metformin and sulfonylureas. CONCLUSION: In this report we found
      that nearly one third of patients with type DM 2 had CKD and in a significant
      percentage of them OADs were prescribed even if they were in K/DIGO CKD stage 3
      and 4.

PMID- 24721943
TI  - Holmium:YAG laser ablation combined intraurethral fluorouracil perfusion as
      treatment option for intraurethral Condyloma acuminata in men.
AB  - AIM: Intraurethral condylomata acuminata (CA) is caused by human papilloma virus
      (HPV) infection which is transmitted by close physical and sexual contact. CA is
      often difficult to cure. There is limited research on the treatment of the
      patients with intraurethral CA. Here, we have reviewed our experiences on the
      treatment of intraurethral condylomatous with Holmium:YAG Laser ablation. A new
      and convenient mean of administering fluorouracil and lidocaine for the treatment
      of intraurethral condyloma acuminata is discussed. This study aimed to evaluate
      the experience and efficacy of Holmium:YAG Laser ablation with ureteroscopy and
      local administration of fluorouracil in the treatment of patients with
      intraurethral CA. The effects were investigated based on the rate of cure and
      relapse and the incidence of complications. METHODS: The study included patients
      with intraurethral condylomatous who had undergone Holmium:YAG Laser ablation and
      intraurethral perfusion of fluorouracil. From May 2005 to October 2008, 25
      patients (mean age 31.3 years, 19-63 years) with cystourethroscopy confirmed
      extensive lesions at the anterior urethra and biopsy of the lesions was
      compatible with condyloma acuminata. They all underwent Holmium:YAG Laser
      ablation with a transurethral Wolf 8/9.8 Fr rigid ureteroscope. And a week later,
      the patients initially accepted intraurethral installation of the mixture
      containing 1% fluorouracil and 1% tetracaine hydrochloride gel (lubricating
      jelly) in a volume of 20 mL. This mixture was given intraurethrally once weekly,
      and tip of the penis was clamped immediately to close the urethral meatus after
      administration by using an occlusive penile clamp and was retained for 20
      minutes. Six treatments were given initially and after six weeks of rest, another
      cycle of six weekly treatments was given. RESULTS: Ureteroscopic Holmium laser
      ablation was successfully performed in all patients with multifocal intraurethral
      CA. Mean CA warts body size was 3 mm (2-8) in diameter. Mean operative time was
      22.8 minutes (range 13-41). No major intraoperative complications occurred.
      Intraurethral installation was well tolerated, although six patients complained
      occasional urethral pain while urinating. Three relapses in a 2-5 weeks of follow
      up underwent repeat holmium laser ablation and installation of the fluorouracil
      mixture. In an average of six months of follow-up, the patients have no ureteral
      stricture or relapse of the CA. CONCLUSION: The results of this study suggest
      that holmium:YAG laser ablation of the intraurethral CA combined with
      intraurethral perfusion of 5-fluorouracil and tetracaine hydrochloride gel
      mixture is an effective and safer therapy with a lower relapse rate for treatment
      of intraurethral CA.

PMID- 24721944
TI  - Feasibility of felt application for renorrhaphy after laparoscopic partial
      nephrectomy.
AB  - AIM: Laparoscopic partial nephrectomy (LPN) has become a well-established
      treatment for selected renal malignancies. Aim of the study was to explore
      feasibility of the application of haemostatic felt pledgets during renorrhaphy
      after Laparoscopic Partial Nephrectomy (LPN) and evaluate its efficacy. METHODS:
      Between May 2008 and December 2011, 42 patients underwent LPN as a treatment for
      renal tumors by a single surgeon. Tumor size and location were assessed by
      contrast enhanced computed tomography (CT) scan. A rolled Tabotamp was placed on
      the tumor bed; 2/0 Vycril sutures, secured with 5mm Hem-o-lok clips, were used to
      perform the renorrhaphy. 7.9x7.9 mm (5/16"x5/16") felt pledgets were placed
      between the hem-o-lok clips and the renal parenchyma on both needle entrance
      sites. W.i.t., EBL, OR time, post-operative complications and hospital stay were
      recorded. RESULTS: Mean w.i.t. was 21+/-5 min, mean OR time 151+/-52 min, while
      EBL was 162+/-56 cc. Surgical complications were recorded in 11/42 (26%; Clavien
      Dindo classification: II-III). Three patients experienced postoperative ileus, 3
      had a urinary leakage, 1 a wound infection and 4 tumor bed bleeding: of these, 2
      required blood transfusions, 1 was managed by embolization and 1 underwent
      nephrectomy. Mean LOS was 2 days. CONCLUSION: The application of hemostatic felt
      pledgets during renorrhaphy after LPN is feasible and safe. This technique may
      reduce cortical bleeding, and could ameliorate surgical outcomes.

PMID- 24721945
TI  - Evaluation of equations that estimate glomerular filtration rate in renal
      transplant recipients.
AB  - AIM: The accuracy of equations that estimate the glomerular filtration rate (GFR)
      in renal transplant patients has not been established; thus their performance was
      assessed in stable renal transplant patients. METHODS: Renal transplant patients
      (N.=213) with stable graft function were enrolled. The Chronic Kidney Disease
      Epidemiology Collaboration (CKD-EPI) equation was used as the reference method
      and compared with the Cockcroft-Gault (CG), Modification of Diet in Renal Disease
      (MDRD), Mayo Clinic (MC) and Nankivell equations. Bias, accuracy and concordance
      rates were determined for all equation relative to CKD-EPI. RESULTS: Mean
      estimated GFR values of the equations differed significantly from the CKD-EPI
      values, though the correlations with the reference method were significant.
      Values of MDRD differed from the CG, MC and Nankivell estimations. The best
      agreement to classify the chronic kidney disease (CKD) stages was for the MDRD
      (Kappa=0.649, P<0.001), and for the other equations the agreement was moderate.
      The MDRD had less bias and narrower agreement limits but underestimated the GFR
      at levels above 60 mL/min/1.73 m2. Conversely, the CG, MC and Nankivell equations
      overestimated the GFR, and the Nankivell equation had the worst performance. The
      MDRD equation P15 and P30 values were higher than those of the other equations
      (P<0.001). CONCLUSION: Despite their correlations, equations estimated the GFR
      and CKD stage differently. The MDRD equation was the most accurate, but the sub
      optimal performance of all the equations precludes their accurate use in clinical
      practice.

PMID- 24721946
TI  - Total ureteral replacement by means of Boari vesical flap and psoas hitching: a
      case report.

PMID- 24721947
TI  - Comprehensive proteomic analysis of white blood cells from chikungunya fever
      patients of different severities.
AB  - BACKGROUND: Chikungunya fever (CHIKF) is a recently re-emerged mosquito
      transmitted viral disease caused by the chikungunya virus (CHIKV), an Alphavirus
      belonging to the family Togaviridae. Infection of humans with CHIKV can result in
      CHIKF of variable severity, although the factors mediating disease severity
      remain poorly defined. METHODS: White blood cells were isolated from blood
      samples collected during the 2009-2010 CHIKF outbreak in Thailand. Clinical
      presentation and viral load data were used to classify samples into three groups,
      namely non chikungunya fever (non-CHIKF), mild CHIKF, and severe CHIKF. Five
      samples from each group were analyzed for protein expression by GeLC-MS/MS.
      RESULTS: CHIKV proteins (structural and non-structural) were found only in CHIKF
      samples. A total of 3505 human proteins were identified, with 68 proteins only
      present in non-CHIKF samples. A total of 240 proteins were found only in CHIKF
      samples, of which 65 and 46 were found only in mild and severe CHIKF samples
      respectively. Proteins with altered expression mapped predominantly to cellular
      signaling pathways (including toll-like receptor and PI3K-Akt signaling) although
      many other processes showed altered expression as a result of CHIKV infection.
      Expression of proteins consistent with the activation of the inflammasome was
      detected, and quantitation of (pro)-caspase 1 at the protein and RNA levels
      showed an association with disease severity. CONCLUSIONS: This study confirms the
      infection of at least a component of white blood cells by CHIKV, and shows that
      CHIKV infection results in activation of the inflammasome in a manner that is
      associated with disease severity.

PMID- 24721948
TI  - The effects of non-thermal atmospheric pressure plasma irradiation on expression
      levels of matrix metalloproteinases in benign melanocytic tumors in RET
      transgenic mice.

PMID- 24721949
TI  - A comprehensive study of oculocutaneous albinism type 1 reveals three previously
      unidentified alleles on the TYR gene.
AB  - BACKGROUND: Oculocutaneous albinism (OCA) is a congenital genetic disorder
      characterized by defects in melanin production. OCA type 1 (OCA1) is the most
      serious and common type of OCA. This study characterized mutations associated
      with OCA1 in a series of Chinese patients. METHODS: We recruited 41 unrelated
      patients with OCA and 100 healthy subjects from the Chinese Han population.
      Genomic DNA was extracted from their blood samples. Mutational analysis of
      tyrosinase (TYR) genes was conducted using polymerase chain reaction (PCR) and
      direct sequencing, specifically to test the 100 control subjects and exclude the
      possibility of polymorphism. Mutational analysis and bioinformatics study were
      performed in TYR mutations. RESULTS: Among the 24 (58.5%) patients with OCA1, 21
      different TYR mutations were identified, including three previously unidentified
      alleles (PUAs): one frameshift mutation (c.216delA) and two missense mutations
      (A241T and N364K). The proband mutation A241T carries three possible mutations in
      complex OCA. CONCLUSION: The findings of this study expand current knowledge and
      data of mutations associated with OCA1 in China and allow us to estimate or
      explore the mutation spectrum and relative frequencies of the TYR gene in the
      Chinese population.

PMID- 24721950
TI  - Nematode Hsp90: highly conserved but functionally diverse.
AB  - Nematodes are amongst the most successful and abundant organisms on the planet
      with approximately 30 000 species described, although the actual number of
      species is estimated to be one million or more. Despite sharing a relatively
      simple and invariant body plan, there is considerable diversity within the
      phylum. Nematodes have evolved to colonize most ecological niches, and can be
      free-living or can parasitize plants or animals to the detriment of the host
      organism. In this review we consider the role of heat shock protein 90 (Hsp90) in
      the nematode life cycle. We describe studies on Hsp90 in the free-living nematode
      Caenorhabditis elegans and comparative work on the parasitic species Brugia
      pahangi, and consider whether a dependence upon Hsp90 can be exploited for the
      control of parasitic species.

PMID- 24721952
TI  - [Motivating the medical scientific research in Peru].

PMID- 24721951
TI  - Mast cell-derived serine proteinase regulates T helper 2 polarization.
AB  - Although mast cells play a critical role in allergic reactions, the cells are
      also involved in the protective immunity in the body. This study aims to
      investigate the role of mast cells in immune regulation during aberrant T helper
      (Th)2 responses. In this study, an adoptive antigen-specific Th2 response model
      was established with mast cell-deficient mice to test the role of mast cell in
      the immune regulation. Cell culture was employed to test the role of mast cells
      in the modulation of the expression of B cell lymphoma 6 protein (Bcl-6) in Th2
      cells. The results showed that after adoptive transfer with immune cells, the
      mast cell-deficient mice showed stronger Th2 pattern responses in the intestine
      than that in the mast cell-sufficient mice. Mast cell-derived mouse mast cell
      protease-6 increased the expression of Bcl-6 in Th2 cells. Bcl-6 inhibited the
      expression of GATA-3 in Th2 cells, subsequently, forkhead box P3 was increased
      and the Th2 cytokines were reduced in the cells; the cells thus showed the immune
      regulatory properties similar to regulatory T cells. We conclude that bedsides
      initiating immune inflammation, mast cells also contribute to the immune
      regulation on Th2 polarization. 

PMID- 24721953
TI  - [Recurrence rate of Helicobacter pylori infection two years after successful
      eradication in Peruvian patients presenting with postprandial distress syndrome].
AB  - INTRODUCTION: The general reported recurrence rate of H. pylori infection in Peru
      is high, implying that the long term effectiveness of anti H. pylori therapy is
      lower than expected. This would lead to an increase in the prevalence of gastric
      cancer and other associated pathologies. MATERIALS AND METHODS: This is a
      prospective cohort study including Peruvian patients with postprandial distress
      and H. pylori infection confirmed by gastric biopsy who recieved treatment and
      achieved bacterial eradication. Two years after the initial diagnosis, patients
      were contacted to determine the recurrence rate of H. pylori infection through
      the Urea breath test. RESULTS: 101 /129 of the patients that were infected with
      H. pylori had a successful eradication of the infection and 28/129 failed to
      eradicate the bacteria. The effectiveness rate of treatment was 77.2%. Two years
      after successful eradication we were able to contact 65/101 participants, 5 of
      them presented positive urea breath tests (recurrence rate of infection of 7.7%)
      (IC 1.5%-13.5%, alpha = 0.05). The annual recurrence rate was 3.85% per year/
      patient. 94% of the patients in the cohort came from poor city areas, 95.4% had
      drinking water at home and 90.8% drank boiled drinking water on a daily basis.
      CONCLUSIONS: The recurrence rate of H. pylori in some populations of Peru is
      lower than expected and comparable with developed countries.

PMID- 24721954
TI  - [Diagnostic of ascites due to portal hypertension: accuracy of the serum-ascites
      albumin gradient and protein analises in ascitic fluid].
AB  - OBJECTIVE: To evaluate the diagnostic accuracy of the Serum-Ascites Albumin
      Gradient (GASA), Protein Concentration in the Ascitic Fluid (PTLA), Albumin
      Concentration in the ascitic fluid (CAA) and the Protein Ascites/Serum Ratio
      (IPAS) for the diagnosis of ascites due to portal hypertension. MATERIALS AND
      METHODS: it was an observational and retrospective study of validation of
      diagnostic tests. The study population was patients from a National Public Health
      Hospital Daniel Alcides Carrion of Callao, Peru, during the period January to
      December of 2012, patients over 15 years old with a diagnosis of ascites which
      samples were taken for study by paracentesis with an standard technique, it was
      analyzed total protein and albumin, as well as study of total protein and albumin
      in blood. We obtained the diagnostic accuracy, sensitivity, specificity, PPV and
      NPV of the Serum-Ascites Albumin Gradient (GASA), Protein Concentration in the
      Ascitic Fluid (PTLA), Albumin Concentration in the ascitic fluid (CAA) and the
      Protein Ascites/Serum Ratio (IPAS) for the diagnosis of ascites due to portal
      hypertension. To determine ascites by HTP as diagnostic tests we took into
      account: GASA >= 1.1, PTLA <2.5, CAA <1.1 or IPAS< 0.5. RESULTS: There were 126
      patients diagnosed with ascites, 10 patients was excluded for having incomplete
      data. Of the 116 patients, the average age was 53.03 +/- 15.73 years old, male 65
      (56%) and female 51 (44%). 61 (52%) had ascites due to portal hypertension from
      liver cirrhosis, and 55 (48%) of ascites due to NO HTP. The sensitivity and
      specificity for GASA was 93% and 47% respectively, for PTLA was 80% and 89%
      respectively, for CAA was 85% and 87% respectively and for the IPAS was 83% and
      80% respectively. The area under the ROC curve for GASA was 0.70, ATPL was 0.84,
      IPAS was 0.81 and CAA was 0.86, we found statistically significant differences
      between GASA compared to the other three parameters (p<0.01 ). CONCLUSION: The
      diagnostic accuracy of CAA, ATPL and IPAS is higher than the GASA to discriminate
      between ascites due to HTP or NO HTP, so that they could be used in clinical
      practice alone or together to achieve a diagnostic approach more successful.

PMID- 24721955
TI  - [Knowledge on non alcoholic fatty liver disease in general practitioners from two
      districts of Chiclayo, Peru, during 2012].
AB  - INTRODUCTION: Nonalcoholic fatty liver disease (NAFLD) is a high prevalent
      disease associated with the metabolic syndrome. It is unknown whether general
      practitioners have an appropriate diagnostic and therapeutic approach to this
      pathology. OBJECTIVE: To determine the level of knowledge on NAFLD of general
      practitioners of two districts of the province of Chiclayo during 2012. MATERIAL
      AND METHODS: Cross sectional design; 60 practitioners were selected and
      interviewed by a non-probabilistic consecutive sampling, using a validated
      instrument of 13 questions. Data were processed using SPSS v15. RESULTS: Only in
      45% of the general practitioners a sufficient knowledge was found. No association
      was found between the level of knowledge with the university of origin, the
      number of years of graduated nor the antecedent of previously had diagnosed at
      least one case of NAFLD. CONCLUSIONS: The level of knowledge in NAFLD in the
      general practitioners interviewed from Chiclayo was insufficient.

PMID- 24721956
TI  - [Lower prevalence of Helicobacter pylori infection observed in patients with
      erosive esophagitis].
AB  - OBJECTIVES: To investigate the prevalence of helicobacter pylori infection and
      the histological type of gastritis in patients with erosive esophagitis and
      compare these findings with a control group without esophagitis. MATERIALS AND
      METHODS: Prospective study in the settings of a private clinic in Lima, Peru.
      Each esophagitis and control patient had two biopsies taken from the antrum, two
      from the corpus as well as two additional samples for the ureasa (CLO) test. If
      any of the samples was positive for helicobacter, the patient was considered
      infected. The histological type of gastritis was assessed in the biopsies.
      RESULTS: 140 adult patients (69% males, mean age 48 years) with endoscopically
      proven esophagitis and 140 control cases, matched by age and sex, were included.
      A lower prevalence of helicobacter infection was found in the esophagitis group
      (27 vs. 44% p= 0.004).The risk for esophagitis was also lower in the patients
      with helicobacter OR: 0.48 IC95% (0.28 - 0.82. A higher percentage of normal
      gastric histology was found in the patients with esophagitis (44 vs. 31% p=
      0.036). In 16 patients the erosive esophagitis was developed "de novo", after the
      eradication of helicobacter. CONCLUSIONS: A lower prevalence of helicobacter
      infection and a higher percentage of normal gastric mucosa were found in patients
      with endoscopic proven erosive esophagitis.

PMID- 24721957
TI  - [Assesing the effect of Lepidium meyenii "Maca" on the gastric mucosa in patients
      with functional dyspepsia].
AB  - OBJECTIVE: The present study was designed to determine the histological effect of
      Lepidium meyenii "Maca" on the gastric mucosa in patients with functional
      dyspepsia. MATERIAL AND METHODS: This study consists of a clinical case series,
      in which the effect of Maca on the gastric histopathology of 29 Peruvian patients
      diagnosed with functional dyspepsia was examined. The presence of H. pylori, as
      well as the degree and depth of the gastric mucosa inflammation was evaluated
      from biopsies obtained before and after the treatment based solely of Maca 3
      grams per day for four weeks. RESULTS: Average values of the degree and depth of
      mucosal inflammation before and after the treatment were compared showing no
      statistical difference among the samples. Sixteen patients were infected with H.
      pylori, and they remained infected after the treatment with Maca. CONCLUSIONS: A
      four week long treatment with Maca does not produce significant changes on
      gastric mucosa of patients with functional dyspepsia, neither on H. pylori
      eradication.

PMID- 24721958
TI  - [Introduction to traditional meta-analysis].
AB  - Currently there is a steady growth of scientific information in medicine which
      unable complete knowledge of all the articles published. Meta-analysis are
      studies that aim to compile all available information, grouping them according to
      a specific outcome, and evaluating it through methodological quality tools. Its
      main objective is to estimate a summary effect size after combining the
      individual results of each study selected under a sufficiently valid statistical
      analysis. The following article is to describe the basic and fundamental concepts
      of traditional meta-analysis, taking this information as input for future reviews
      of "advanced methods in meta-analysis", such as indirect meta-analysis or network
      analysis.

PMID- 24721959
TI  - Difficult cannulation: what should I do before EUS guided access?
AB  - Selective cannulation of the common bile duct can be difficult, so multiple
      strategies have been developed to overcome the situation. In this review we
      analize the different strategies that can be used like different papillotome
      instead of the standard catheter, precut papillotomy using precut needle knives
      or precut papillotome, transpancreatic papillary septotomy, and stenting of the
      pancreatic duct. Bile duct cannulation remains an important benchmark of
      successful ERCP. Alternative biliary access indication and its use is very
      important If biliary cannulation remains unsuccessful.The suprapapillary puncture
      is a promissory technique. It's important to have in mind that the goal of all
      techniques is to provide acute pancreatitis decrease.

PMID- 24721960
TI  - [Intestinal disease due to Mycobacterium avium in a patient with HIV/AIDS].
AB  - We report the first case of colitis due to Mycobacterium avium in a Peruvian
      patient with HIV/AIDS. 

PMID- 24721961
TI  - [Severe acute pancreatitis associated with gallbladder gangrene].
AB  - We present a diabetic patient who developed severe acute pancreatitis associated
      to gallbladder gangrene, in this case we assessed the applicability of
      classification criteria and management of the pathways for acute pancreatitis and
      also we suggest some topics that could be investigated in the future. 

PMID- 24721962
TI  - [Bouveret Syndrome. First case diagnosed in Santa Maria del Socorro, Ica, Peru].
AB  - We are presenting an case of a patient with upper gastrointestinal bleeding
      presented as hematemesis preceded by profuse vomiting secondary to a duodenal
      obstruction, caused by an impacted giant biliary stone in the duodenal bulb
      (Bouveret syndrome). The diagnosis was made during an upper gastrointestinal
      endoscopy and confirmed by surgery. We report and discuss this case as it is the
      first presentation in our institution. 

PMID- 24721963
TI  - [Portal hypertension in pregnancy: report of a case].
AB  - The coexistence of pregnancy and liver disease represents a complex clinical
      situation. Pregnancy develops hypervolemic state due to increased splachnic blood
      flow, which contributes to increased portal pressure transmitted to collateral
      veins that increase the risk of variceal bleeding in these patients. We report
      the case of a 39 years old patient in the sixth pregnancy and without any
      previous medical history that presented pre-sinusoidal portal hypertension, and
      thanks to appropriate multidisciplinary management had an uncomplicated delivery.
      We review the literature relevant to the case. 

PMID- 24721964
TI  - [GlobalSurg Proyect: an opportunity to encourage surgical research in Peru].

PMID- 24721965
TI  - Ras GTPase-like protein MglA, a controller of bacterial social-motility in
      Myxobacteria, has evolved to control bacterial predation by Bdellovibrio.
AB  - Bdellovibrio bacteriovorus invade Gram-negative bacteria in a predatory process
      requiring Type IV pili (T4P) at a single invasive pole, and also glide on
      surfaces to locate prey. Ras-like G-protein MglA, working with MglB and RomR in
      the deltaproteobacterium Myxococcus xanthus, regulates adventurous gliding and
      T4P-mediated social motility at both M. xanthus cell poles. Our bioinformatic
      analyses suggested that the GTPase activating protein (GAP)-encoding gene mglB
      was lost in Bdellovibrio, but critical residues for MglA(Bd) GTP-binding are
      conserved. Deletion of mglA(Bd) abolished prey-invasion, but not gliding, and
      reduced T4P formation. MglA(Bd) interacted with a previously uncharacterised
      tetratricopeptide repeat (TPR) domain protein Bd2492, which we show localises at
      the single invasive pole and is required for predation. Bd2492 and RomR also
      interacted with cyclic-di-GMP-binding receptor CdgA, required for rapid prey
      invasion. Bd2492, RomR(Bd) and CdgA localize to the invasive pole and may
      facilitate MglA-docking. Bd2492 was encoded from an operon encoding a TamAB-like
      secretion system. The TamA protein and RomR were found, by gene deletion tests,
      to be essential for viability in both predatory and non-predatory modes. Control
      proteins, which regulate bipolar T4P-mediated social motility in swarming groups
      of deltaproteobacteria, have adapted in evolution to regulate the anti-social
      process of unipolar prey-invasion in the "lone-hunter" Bdellovibrio. Thus GTP
      binding proteins and cyclic-di-GMP inputs combine at a regulatory hub, turning on
      prey-invasion and allowing invasion and killing of bacterial pathogens and
      consequent predatory growth of Bdellovibrio.

PMID- 24721966
TI  - Availability of illicit tobacco in small retail outlets before and after the
      implementation of Australian plain packaging legislation.
AB  - OBJECTIVE: We aimed to assess change in the availability of illicit tobacco in
      small mixed business retail outlets following the December 2012 introduction of
      plain packaging in Australia. METHODS: 303 small retail outlets were visited in
      June and September 2012 (baseline months), and in December 2012 and February,
      April and July 2013. Fieldworkers requested a particular low-cost brand of
      cigarettes and then pressed the retailer for an 'even cheaper' brand. The
      cheapest pack of cigarettes offered was purchased and later examined to assess
      any divergence from prescribed Australian packaging regulations. The price paid
      was compared with tax liability and recommended retail price for the particular
      brand and pack size. In a sub-set of 179 stores, fieldworkers then asked the
      retailer about availability of unbranded (chop-chop) tobacco. RESULTS: Thirteen
      (2.2%) of 598 packs purchased pre-plain packaging were either non-compliant with
      Australian health warnings and/or suspiciously priced. Four packs (1.3%) of 297
      met either or both criteria in the December implementation month, and five (0.6%)
      of 878 did so in the three collection months following implementation. Chop-chop
      was offered upon enquiry on 0.6% (n=2) of 338 occasions prior to implementation,
      0.6% (n=1) of 170 occasions in the December 2012 implementation month, and 0.6%
      (n=3) of 514 occasions postimplementation. The likelihood of a 'positive'
      response (either an offer to sell or information about where unbranded tobacco
      may be purchased) did not differ across preimplementation, during-implementation
      and postimplementation waves. CONCLUSIONS: Overall, packs judged likely to be
      illicit were sold in response to requests for cheapest available packs on fewer
      than one percent of occasions. Offers to sell unbranded tobacco were rare. No
      change in availability of illicit tobacco was observed following implementation
      of plain packaging.

PMID- 24721967
TI  - Preference for flavoured cigar brands among youth, young adults and adults in the
      USA.
AB  - BACKGROUND: While cigarette consumption in the USA continues to decline, cigar
      consumption has increased. Tobacco-trade publications suggest that flavoured
      cigars are driving the recent growth in cigar consumption. Limited survey data
      exist to explore flavoured cigar preferences among youth and adults. METHODS:
      This study used the 2010-2011 National Survey on Drug Use and Health (NSDUH) and
      Nielsen market scanner data. The NSDUH sample consisted of 6678 past 30-day cigar
      smokers who reported smoking a usual brand of cigars. NSDUH contains a measure on
      usual cigar brand smoked and was merged with Nielsen data to estimate the per
      cent of each cigar brand's market share that is flavoured. RESULTS: Multivariate
      analyses indicate that youth, young adults, females, blacks, cigarette smokers,
      blunt users and daily cigar smokers are significantly more likely to report a
      usual cigar brand that is flavoured. Preference for a usual brand that produces
      flavoured cigars decreases significantly with age. CONCLUSIONS: This study finds
      recent growth in flavoured cigar consumption and preference among youth and young
      adults for cigar brands that are flavoured. These findings underscore the need to
      expand monitoring of product attributes as well as individual-level cigar use
      behaviours captured through population surveillance.

PMID- 24721968
TI  - Continued implications of taxing roll-your-own tobacco as pipe tobacco in the
      USA.
AB  - BACKGROUND: In 2009, a US$21.95 per pound disparity was created in the Federal
      excise tax between roll-your-own cigarette tobacco (RYO) and pipe tobacco in the
      USA. After this disparity was created, pipe tobacco sales increased and RYO sales
      declined as some manufacturers repackaged roll-your-own tobacco as pipe tobacco
      and retailers began to offer cigarette rolling machines for consumers to use. A
      Federal law was passed in 2012 limiting the availability of these machines,
      however, it was unclear what impact this law had on the sales of roll-your-own
      tobacco labelled as pipe tobacco. METHODS: The quantity of RYO sold as pipe
      tobacco each month was estimated using objective data on Federal excise taxes.
      RESULTS: From April 2009 through June 2013, 107 million pounds of RYO were sold
      as pipe tobacco, reducing Federal excise tax collections by US$2.36 billion. The
      amount of RYO taxed as pipe tobacco climbed steadily and then levelled off
      following the July 2012 Federal law. CONCLUSIONS: The Federal law did not correct
      the market shift that occurred in pipe and RYO sales beginning in 2009. Even
      without access to commercial rolling machines, smokers are continuing to take
      advantage of the tax disparity. Without a solution, states will continue to lose
      revenue, and smokers who would otherwise quit will continue to have a low-cost
      alternative product available for purchase. Potential solutions include: (1) US
      Treasury Department distinguishing between RYO and pipe tobacco based on physical
      characteristics and (2) changing the Federal excise tax so that RYO and pipe
      tobacco are taxed at the same rate.

PMID- 24721969
TI  - Introductory paragraph - volume 28, issue 5.

PMID- 24721970
TI  - Diagnosis of bladder cancer and prediction of survival by urinary metabolomics.
AB  - Bladder cancer (BC) is a common cancer but diagnostic modalities, such as
      cystoscopy and urinary cytology, have limitations. Here, high-performance liquid
      chromatography-quadrupole time-of-flight mass spectrometry (HPLC-QTOFMS) was used
      to profile urine metabolites of 138 patients with BC and 121 control subjects (69
      healthy people and 52 patients with hematuria due to non-malignant diseases).
      Multivariate statistical analysis revealed that the cancer group could be clearly
      distinguished from the control groups on the basis of their metabolomic profiles,
      even when the hematuric control group was included. Patients with muscle-invasive
      BC could also be distinguished from patients with non-muscle-invasive BC on the
      basis of their metabolomic profiles. Successive analyses identified 12
      differential metabolites that contributed to the distinction between the BC and
      control groups, and many of them turned out to be involved in glycolysis and
      betaoxidation. The association of these metabolites with cancer was corroborated
      by microarray results showing that carnitine transferase and pyruvate
      dehydrogenase complex expressions are significantly altered in cancer groups. In
      terms of clinical applicability, the differentiation model diagnosed BC with a
      sensitivity and specificity of 91.3% and 92.5%, respectively, and comparable
      results were obtained by receiver operating characteristic analysis (AUC =
      0.937). Multivariate regression also suggested that the metabolomic profile
      correlates with cancer-specific survival time. The excellent performance and
      simplicity of this metabolomics-based approach suggests that it has the potential
      to augment or even replace the current modalities for BC diagnosis. 

PMID- 24721972
TI  - Hepatitis C could be virtually eliminated by 2030, experts believe.

PMID- 24721973
TI  - Autophagy researchers.

PMID- 24721971
TI  - Real time RT-PCR assays for detection and typing of African horse sickness virus.
AB  - Although African horse sickness (AHS) can cause up to 95% mortality in horses,
      naive animals can be protected by vaccination against the homologous AHSV
      serotype. Genome segment 2 (Seg-2) encodes outer capsid protein VP2, the most
      variable of the AHSV proteins. VP2 is also a primary target for AHSV specific
      neutralising antibodies, and consequently determines the identity of the nine
      AHSV serotypes. In contrast VP1 (the viral polymerase) and VP3 (the sub-core
      shell protein), encoded by Seg-1 and Seg-3 respectively, are highly conserved,
      representing virus species/orbivirus-serogroup-specific antigens. We report
      development and evaluation of real-time RT-PCR assays targeting AHSV Seg-1 or Seg
      3, that can detect any AHSV type (virus species/serogroup-specific assays), as
      well as type-specific assays targeting Seg-2 of the nine AHSV serotypes. These
      assays were evaluated using isolates of different AHSV serotypes and other
      closely related orbiviruses, from the 'Orbivirus Reference Collection' (ORC) at
      The Pirbright Institute. The assays were shown to be AHSV virus-species-specific,
      or type-specific (as designed) and can be used for rapid, sensitive and reliable
      detection and identification (typing) of AHSV RNA in infected blood, tissue
      samples, homogenised Culicoides, or tissue culture supernatant. None of the
      assays amplified cDNAs from closely related heterologous orbiviruses, or from
      uninfected host animals or cell cultures. 

PMID- 24721974
TI  - Use of MRI to guide electrophysiology procedures.

PMID- 24721975
TI  - Non-alcoholic fatty liver disease, metabolic syndrome and subclinical
      cardiovascular changes in the general population.
AB  - OBJECTIVE: The effect of non-alcoholic fatty liver disease (NAFLD) on
      cardiovascular system remains controversial. We investigated the independent
      contribution of NAFLD to cardiovascular structure and function in the general
      population. METHODS: A total of 1886 participants without known cardiovascular
      disease were enrolled from the Korean Genome Epidemiology Study. The participants
      were divided into four groups, based on the presence of NAFLD, metabolic syndrome
      (MetS), neither or both. NAFLD was diagnosed by CT. Changes in cardiovascular
      structure and function were assessed by tissue Doppler imaging (TDI)
      echocardiography, carotid ultrasound and brachial-ankle pulse wave velocity
      (baPWV). RESULTS: In multivariate analyses, subjects with both NAFLD and MetS had
      a higher E/Ea ratio and baPWV, as well as a lower TDI Ea velocity (all p<0.001)
      than those with neither NAFLD nor MetS. Subjects with either NAFLD or MetS also
      showed significant differences in TDI Ea velocity and baPWV (all p<0.05).
      However, no significant differences of carotid intima-media thickness (CIMT)
      values were seen among the four groups. Multivariate linear regression revealed
      that both NAFLD and MetS were independent predictors of TDI Ea velocity and baPWV
      (all p<0.001). Both MetS and NAFLD were not a determinant of CIMT. CONCLUSIONS:
      NAFLD was associated with early alterations of cardiovascular system, independent
      of established cardiovascular risk factors and MetS.

PMID- 24721977
TI  - Screening Electronic Health Record-Related Patient Safety Reports Using Machine
      Learning.
AB  - INTRODUCTION: The objective of this study was to develop a semiautomated approach
      to screening cases that describe hazards associated with the electronic health
      record (EHR) from a mandatory, population-based patient safety reporting system.
      METHODS: Potentially relevant cases were identified through a query of the
      Pennsylvania Patient Safety Reporting System. A random sample of cases were
      manually screened for relevance and divided into training, testing, and
      validation data sets to develop a machine learning model. This model was used to
      automate screening of remaining potentially relevant cases. RESULTS: Of the 4
      algorithms tested, a naive Bayes kernel performed best, with an area under the
      receiver operating characteristic curve of 0.927 +/- 0.023, accuracy of 0.855 +/-
      0.033, and F score of 0.877 +/- 0.027. DISCUSSION: The machine learning model and
      text mining approach described here are useful tools for identifying and
      analyzing adverse event and near-miss reports. Although reporting systems are
      beginning to incorporate structured fields on health information technology and
      the EHR, these methods can identify related events that reporters classify in
      other ways. These methods can facilitate analysis of legacy safety reports by
      retrieving health information technology-related and EHR-related events from
      databases without fields and controlled values focused on this subject and
      distinguishing them from reports in which the EHR is mentioned only in passing.
      CONCLUSIONS: Machine learning and text mining are useful additions to the patient
      safety toolkit and can be used to semiautomate screening and analysis of
      unstructured text in safety reports from frontline staff.

PMID- 24721976
TI  - Telomerase enzymatic component hTERT shortens long telomeres in human cells.
AB  - Telomere lengths are tightly regulated within a narrow range in normal human
      cells. Previous studies have extensively focused on how short telomeres are
      extended and have demonstrated that telomerase plays a central role in elongating
      short telomeres. However, much about the molecular mechanisms of regulating
      excessively long telomeres is unknown. In this report, we demonstrated that the
      telomerase enzymatic component, hTERT, plays a dual role in the regulation of
      telomere length. It shortens excessively long telomeres and elongates short
      telomeres simultaneously in one cell, maintaining the optimal telomere length at
      each chromosomal end for efficient protection. This novel hTERT-mediated telomere
      shortening mechanism not only exists in cancer cells, but also in primary human
      cells. The hTERT-mediated telomere shortening requires hTERT's enzymatic
      activity, but the telomerase RNA component, hTR, is not involved in that process.
      We found that expression of hTERT increases telomeric circular DNA formation,
      suggesting that telomere homologous recombination is involved in the telomere
      shortening process. We further demonstrated that shelterin protein TPP1 interacts
      with hTERT and recruits hTERT onto the telomeres, suggesting that TPP1 might be
      involved in regulation of telomere shortening. This study reveals a novel
      function of hTERT in telomere length regulation and adds a new element to the
      current molecular model of telomere length maintenance. 

PMID- 24721978
TI  - Pharmacy Survey on Patient Safety Culture: Benchmarking Results.
AB  - OBJECTIVE: This study's objective was to assess the patient safety culture in a
      large, integrated health delivery system's pharmacy department to allow for
      benchmarking with other health systems. METHODS: This was a cross-sectional
      survey conducted in a pharmacy department consisting of staff members who provide
      dispensing, clinical, and support services within an integrated health delivery
      system. The U.S. Agency for Healthcare Research and Quality's 11-composite,
      validated Pharmacy Survey on Patient Safety Culture questionnaire was transcribed
      into an online format. All departmental staff members were invited to participate
      in this anonymous survey. Cronbach alpha and overall results and contrasts
      between dispensing and clinical services staff and dispensing pharmacists and
      technicians/clerks as percentage positive scores (PPSs) are presented.
      Differences in contrasts were assessed with chi tests of association. RESULTS:
      Completed questionnaires were received from 598 (69.9%) of 855 employees.
      Cronbach alpha ranged from 0.55 to 0.90. Overall, the highest and lowest
      composite PPSs were for patient counseling (94.5%) and staffing and work pressure
      (44.7%), respectively. Compared with dispensing service, the clinical service
      participants had statistically higher PPSs for all composites except patient
      counseling, communication about mistakes, and staffing and work pressure (all P >
      0.05). The technicians/clerks had a statistically higher PPS compared with the
      pharmacists for communication about mistakes (P = 0.007). All other composites
      were equivalent between groups. CONCLUSIONS: Patient counseling consistently had
      the highest PPS among composites measured, but opportunities existed for
      improvement in all aspects measured. Future research should identify and assess
      interventions targeted to improving the patient safety culture in pharmacy.

PMID- 24721979
TI  - Vacuum filtration based formation of liquid crystal films of semiconducting
      carbon nanotubes and high performance transistor devices.
AB  - In this paper, we report ultra-thin liquid crystal films of semiconducting carbon
      nanotubes using a simple vacuum filtration process. Vacuum filtration of
      nanotubes in aqueous surfactant solution formed nematic domains on the filter
      membrane surface and exhibited local ordering. A 2D fast Fourier transform was
      used to calculate the order parameters from scanning electron microscopy images.
      The order parameter was observed to be sensitive to the filtration time
      demonstrating different regions of transformation namely nucleation of nematic
      domains, nanotube accumulation and large domain growth.Transmittance versus sheet
      resistance measurements of such films resulted in optical to dc conductivity of
      sigma(opt)/sigma(dc) = 9.01 indicative of purely semiconducting nanotube liquid
      crystal network.Thin films of nanotube liquid crystals with order parameters
      ranging from S = 0.1-0.5 were patterned into conducting channels of transistor
      devices which showed high I(on)/I(off) ratios from 10-19,800 and electron
      mobility values MU(e) = 0.3-78.8 cm(2) (V-s)(-1), hole mobility values MU(h) =
      0.4-287 cm(2) (V-s)(-1). High I on/I off ratios were observed at low order
      parameters and film mass. A Schottky barrier transistor model is consistent with
      the observed transistor characteristics. Electron and hole mobilities were seen
      to increase with order parameters and carbon nanotube mass fractions. A
      fundamental tradeoff between decreasing on/off ratio and increasing mobility with
      increasing nanotube film mass and order parameter is therefore concluded.
      Increase in order parameters of nanotubes liquid crystals improved the electronic
      transport properties as witnessed by the increase in sigma(dc)/sigma(opt) values
      on macroscopic films and high mobilities in microscopic transistors. Liquid
      crystal networks of semiconducting nanotubes as demonstrated here are simple to
      fabricate, transparent, scalable and could find wide ranging device applications.

PMID- 24721981
TI  - Serious photocontact dermatitis induced by topical ketoprofen depends on the
      formulation.
AB  - BACKGROUND: Topical administration of ketoprofen to treat local subcutaneous pain
      significantly reduces gastrointestinal and cardiovascular adverse effects
      associated with oral delivery. However, this benefit must be weighed against the
      risk of photosensitisation/phototoxicity. OBJECTIVE: To substantiate the safety
      and efficacy of topical ketoprofen delivery from a patch. METHODS: Experiments
      were performed, and published information analysed, (a) to confirm the superior
      skin permeability and pharmacological activity of ketoprofen, and (b) to
      demonstrate the lower incidence of ketoprofen photosensitisation/phototoxicity
      when delivered from a topical patch. RESULTS: Ketoprofen's photodegradation
      products were more photoallergic than the drug itself. The period post-ketoprofen
      treatment that skin should be protected from UV radiation (while the drug is
      cleared from the application site) was estimated. CONCLUSIONS: Photosensitisation
      to ketoprofen can be mitigated by a patch formulation, which protects the drug
      from direct UV exposure during skin application, and reduces the formation of
      even more photoallergic photodegradation products.

PMID- 24721980
TI  - Reducing communication delays and improving quality of care with a tuberculosis
      laboratory information system in resource poor environments: a cluster randomized
      controlled trial.
AB  - BACKGROUND: Lost, delayed or incorrect laboratory results are associated with
      delays in initiating treatment. Delays in treatment for Multi-Drug Resistant
      Tuberculosis (MDR-TB) can worsen patient outcomes and increase transmission. The
      objective of this study was to evaluate the impact of a laboratory information
      system in reducing delays and the time for MDR-TB patients to culture convert
      (stop transmitting). METHODS:  SETTING: 78 primary Health Centers (HCs) in Lima,
      Peru. Participants lived within the catchment area of participating HCs and had
      at least one MDR-TB risk factor. The study design was a cluster randomized
      controlled trial with baseline data. The intervention was the e-Chasqui web-based
      laboratory information system. Main outcome measures were: times to communicate a
      result; to start or change a patient's treatment; and for that patient to culture
      convert. RESULTS: 1671 patients were enrolled. Intervention HCs took
      significantly less time to receive drug susceptibility test (DST) (median 11 vs.
      17 days, Hazard Ratio 0.67 [0.62-0.72]) and culture (5 vs. 8 days, 0.68 [0.65
      0.72]) results. The time to treatment was not significantly different, but
      patients in intervention HCs took 16 days (20%) less time to culture convert (p =
      0.047). CONCLUSIONS: The eChasqui system reduced the time to communicate results
      between laboratories and HCs and time to culture conversion. It is now used in
      over 259 HCs covering 4.1 million people. This is the first randomized controlled
      trial of a laboratory information system in a developing country for any disease
      and the only study worldwide to show clinical impact of such a system. TRIAL
      REGISTRATION: ClinicalTrials.gov NCT01201941.

PMID- 24721982
TI  - Age-dependent effects of UCP2 deficiency on experimental acute pancreatitis in
      mice.
AB  - Reactive oxygen species (ROS) have been implicated in the pathogenesis of acute
      pancreatitis (AP) for many years but experimental evidence is still limited.
      Uncoupling protein 2 (UCP2)-deficient mice are an accepted model of age-related
      oxidative stress. Here, we have analysed how UCP2 deficiency affects the severity
      of experimental AP in young and older mice (3 and 12 months old, respectively)
      triggered by up to 7 injections of the secretagogue cerulein (50 MUg/kg body
      weight) at hourly intervals. Disease severity was assessed at time points from 3
      hours to 7 days based on pancreatic histopathology, serum levels of alpha
      amylase, intrapancreatic trypsin activation and levels of myeloperoxidase (MPO)
      in lung and pancreatic tissue. Furthermore, in vitro studies with pancreatic
      acini were performed. At an age of 3 months, UCP2-/- mice and wild-type (WT)
      C57BL/6 mice were virtually indistinguishable with respect to disease severity.
      In contrast, 12 months old UCP2-/- mice developed a more severe pancreatic damage
      than WT mice at late time points after the induction of AP (24 h and 7 days,
      respectively), suggesting retarded regeneration. Furthermore, a higher peak level
      of alpha-amylase activity and gradually increased MPO levels in pancreatic and
      lung tissue were observed in UCP2-/- mice. Interestingly, intrapancreatic trypsin
      activities (in vivo studies) and intraacinar trypsin and elastase activation in
      response to cerulein treatment (in vitro studies) were not enhanced but even
      diminished in the knockout strain. Finally, UCP2-/- mice displayed a diminished
      ratio of reduced and oxidized glutathione in serum but no increased ROS levels in
      pancreatic acini. Together, our data indicate an aggravating effect of UCP2
      deficiency on the severity of experimental AP in older but not in young mice. We
      suggest that increased severity of AP in 12 months old UCP2-/- is caused by an
      imbalanced inflammatory response but is unrelated to acinar cell functions. 

PMID- 24721983
TI  - Assumed white blood cell count of 8,000 cells/MUL overestimates malaria parasite
      density in the Brazilian Amazon.
AB  - Quantification of parasite density is an important component in the diagnosis of
      malaria infection. The accuracy of this estimation varies according to the method
      used. The aim of this study was to assess the agreement between the parasite
      density values obtained with the assumed value of 8,000 cells/MUL and the
      automated WBC count. Moreover, the same comparative analysis was carried out for
      other assumed values of WBCs. The study was carried out in Brazil with 403
      malaria patients who were infected in different endemic areas of the Brazilian
      Amazon. The use of a fixed WBC count of 8,000 cells/MUL to quantify parasite
      density in malaria patients led to overestimated parasitemia and resulted in low
      reliability when compared to the automated WBC count. Assumed values ranging
      between 5,000 and 6,000 cells/MUL, and 5,500 cells/MUL in particular, showed
      higher reliability and more similar values of parasite density when compared
      between the 2 methods. The findings show that assumed WBC count of 5,500
      cells/MUL could lead to a more accurate estimation of parasite density for
      malaria patients in this endemic region. 

PMID- 24721985
TI  - The intriguing host innate immune response: novel anti-parasitic defence by
      neutrophil extracellular traps.
AB  - The capacity of polymorphonuclear neutrophils (PMN) and other leucocytes of the
      innate immune system to expel their DNA in a controlled process into the
      extracellular environment to trap and kill pathogenic microorganisms led to a
      paradigm shift in our comprehension of host leucocyte-pathogen interactions.
      Formation of neutrophil extracellular traps (NETs) has recently been recognized
      as a novel effector mechanism of the host innate immune response against
      microbial infections. Meanwhile evidence has arisen that NET formation is a
      widely spread mechanism in vertebrates and invertebrates and extends not only to
      the entrapment of microbes, fungi and viruses but also to the capture of
      protozoan and metazoan parasites. PMN produce NETs after stimulation with
      mitogens, cytokines or pathogens in a controlled process which depends on
      reactive oxygen species (ROS) and the induction of the Raf-MEK-ERK-mediated
      signalling pathway cascade. NETs consist of nuclear DNA as a backbone decorated
      with histones, antimicrobial peptides, and PMN-specific granular enzymes thereby
      providing an extracellular matrix capable of entrapping and killing invasive
      pathogens. This review is intended to summarize parasite-related data on NETs.
      Special attention will be given to NET-associated mechanisms by which parasites,
      in particular apicomplexa, might be hampered in their ability to reproduce within
      the host cell and complete the life cycle.

PMID- 24721986
TI  - Structural and optical properties of ITO/TiO2 anti-reflective films for solar
      cell applications.
AB  - Indium tin oxide (ITO) and titanium dioxide (TiO2) anti-reflective coatings
      (ARCs) were deposited on a (100) P-type monocrystalline Si substrate by a radio
      frequency (RF) magnetron sputtering. Polycrystalline ITO and anatase TiO2 films
      were obtained at room temperature (RT). The thickness of ITO (60 to 64 nm) and
      TiO2 (55 to 60 nm) films was optimized, considering the optical response in the
      400- to 1,000-nm wavelength range. The deposited films were characterized by X
      ray diffraction (XRD), Raman spectroscopy, field emission scanning electron
      microscopy (FESEM), energy dispersive spectroscopy (EDS), and atomic force
      microscopy (AFM). The XRD analysis showed preferential orientation along (211)
      and (222) for ITO and (200) and (211) for TiO2 films. The XRD analysis showed
      that crystalline ITO/TiO2 films could be formed at RT. The crystallite strain
      measurements showed compressive strain for ITO and TiO2 films. The measured
      average optical reflectance was about 12% and 10% for the ITO and TiO2 ARCs,
      respectively. 

PMID- 24721987
TI  - Statistical power to detect genetic (co)variance of complex traits using SNP data
      in unrelated samples.
AB  - We have recently developed analysis methods (GREML) to estimate the genetic
      variance of a complex trait/disease and the genetic correlation between two
      complex traits/diseases using genome-wide single nucleotide polymorphism (SNP)
      data in unrelated individuals. Here we use analytical derivations and simulations
      to quantify the sampling variance of the estimate of the proportion of phenotypic
      variance captured by all SNPs for quantitative traits and case-control studies.
      We also derive the approximate sampling variance of the estimate of a genetic
      correlation in a bivariate analysis, when two complex traits are either measured
      on the same or different individuals. We show that the sampling variance is
      inversely proportional to the number of pairwise contrasts in the analysis and to
      the variance in SNP-derived genetic relationships. For bivariate analysis, the
      sampling variance of the genetic correlation additionally depends on the harmonic
      mean of the proportion of variance explained by the SNPs for the two traits and
      the genetic correlation between the traits, and depends on the phenotypic
      correlation when the traits are measured on the same individuals. We provide an
      online tool for calculating the power of detecting genetic (co)variation using
      genome-wide SNP data. The new theory and online tool will be helpful to plan
      experimental designs to estimate the missing heritability that has not yet been
      fully revealed through genome-wide association studies, and to estimate the
      genetic overlap between complex traits (diseases) in particular when the traits
      (diseases) are not measured on the same samples. 

PMID- 24721988
TI  - Repeated change-of-direction test for collegiate male soccer players.
AB  - AIM: The aim of the study was to investigate the applicability of a repeated
      change-of-direction (RCoD) test for NCAA Division-I male soccer players. METHODS:
      The RCoD test consisted of 5 diagonal direction changes per repetition with a
      soccer ball to be struck at the end. Each player performed 15 repetitions with
      approximately 10 seconds to jog back between repetitions. Data were collected in
      two sessions. In the first session, 13 players were examined for heart rate
      responses and blood lactate concentrations. In the second session, 22 players
      were examined for the test's ability to discriminate the primary from secondary
      players (78.0+/-16.1 and 10.4+/-13.3 minutes per match, respectively). RESULTS:
      Heart rate data were available only from 9 players due to artifacts. The peak
      heart rate (200.2+/-6.6 beats?min-1: 99.9+/-3.0% maximum) and blood lactate
      concentration (14.8+/-2.4 mmol?L-1 immediately after) resulted in approximately
      3.5 and 6.4-fold increases from the resting values, respectively. These values
      appear comparable to those during intense periods of soccer matches. In addition,
      the average repetition time of the test was found to discriminate the primary
      (4.85+/-0.23 s) from the secondary players (5.10+/-0.24 s) (P=0.02). CONCLUSION:
      The RCoD test appears to induce physiological responses similar to intense
      periods of soccer matches with respect to heart rate and blood lactate
      concentration. Players with better average repetition times tend to be those who
      play major minutes.

PMID- 24721989
TI  - Cardiorespiratory, metabolic and hormonal responses during open-wheel indoor kart
      racing.
AB  - AIM: This study aimed to quantify the cardiorespiratory, metabolic and hormonal
      responses of elite open-wheel indoor kart racers. METHODS: Ten male racers (age:
      21+/-3 yrs; height: 1.92+/-0.06 m, body mass: 76.0+/-5.9 kg) participated in a
      racing tournament. Their peak oxygen uptake and heart rate were assessed by a
      ramp test (100 W, increase 30 W.min-1) in the laboratory. During the racing
      itself, the cardio-respiratory and accelerometer values were recorded and pre-
      and post-race levels of blood lactate and salivary cortisol were determined.
      RESULTS: The average peak values for all of the drivers with respect to oxygen
      uptake and heart rate were 4.5+/-0.8 L.min-1 (56.7+/-7.9 mL.min-1.kg-1) and 193+/
      5 beats.min-1, respectively. Overall, 28.3+/-3.3 laps were completed during 30
      min of racing. Acceleration forces for the entire test averaged 1.20+/-0.51 G
      (maximum: 3.30 G), declining from the first 10 min until the end of racing
      (P<0.03). The oxygen uptake (~20 mL.min-1.kg-1), heart rate (~133 beats.min-1),
      respiratory exchange ratio (~0.96) and ventilation (~70 L.min-1) observed
      indicated moderate cardio-respiratory responses. Blood lactate concentration was
      significantly higher after the race than before but remained at <2 mmol.L-1
      (P<0.01; effect size: 1.62). CONCLUSION: There were no differences between
      salivary cortisol levels before and after the race (P<0.06; effect size: 0.49).
      Directly after the race, the drivers rated their perceived exertion on Borg's
      scale as 11.1+/-1.3. The present data revealed that the psycho-physical exertion
      associated with a 30-min open-wheel indoor kart race is moderate.

PMID- 24721990
TI  - TEI Index in elite sprinters and endurance athletes.
AB  - AIM: Aerobic training has been reported to have a positive effect on myocardial
      performance index. The aim of the present study was to examine the myocardial
      performance index (MPI) in sprinters and endurance athletes. METHODS: A total of
      66 elite male athletes (36 sprinter and 30 endurance athletes) and 33 agematched
      sedentary controls voluntarily participated in the study. The echocardiographic
      evaluation was performed and TEI index was measured as a marker of myocardial
      performance index in all groups. RESULTS: Demographic features, training ages and
      weekly exercise volumes were similar in sprinters and endurance athletes. There
      were no significant differences in terms of diastolic parameters and among the
      groups. In sprinters, isovolumetric relaxation time (IVRT) and isovolumetric
      contraction time (IVCT) were significantly shorter than in controls. In endurance
      athletes, IVCT was significantly shorter than in controls. Both sprinters and
      endurance athletes had longer ET compared with controls. TEI Index was
      significantly lower in sprinters and endurance athletes than in controls.
      CONCLUSION: Our results suggest that both aerobic and anaerobic training seem to
      have a positive effect on myocardial performance. This comparable effect might be
      a result of frequently exercising, especially aerobic exercising in sprinters'
      training programs.

PMID- 24721991
TI  - Risk factors for elbow pain in Little League baseball players: a cross-sectional
      study focusing on developmental factors.
AB  - AIM: The incidence of Little League elbow is increasing. However, the risk
      factors for Little League elbow, especially those related to development have not
      previously been investigated. The purpose of this study was to investigate the
      risk factors for elbow pain in Little League baseball players while focusing on
      the developmental factors. METHODS: A total of 654 baseball players aged 6-12
      years, all male, participated in this study. Participants completed an original
      questionnaire that included items assessing demographic data, developmental
      factors (increase in height and increase in weight over the preceding 12 months),
      and baseball-related factors. Multiple regression analysis was used to identify
      the risk factors for elbow pain during the 12 months prior to the study. RESULTS:
      The data collected for 392 players without omissions or blank answers were
      submitted to statistical analysis. We found that 19.1% of Little League baseball
      players had experienced elbow pain in the 12 months leading up to the study. The
      analysis revealed that height (Odds Ratio [OR], 1.10; 95% confidence interval
      [95%CI], 1.03-1.17) and increase in height (OR, 1.16; 95%CI, 1.00-1.34) were risk
      factors that increased the risk of elbow pain after adjustment for demographic
      data, developmental data, and baseball-related factors. CONCLUSION: Our results
      suggested that an increase over height in the last 12 months may predispose young
      baseball players to elbow pain.

PMID- 24721992
TI  - Future climate scenarios for a coastal productive planktonic food web resulting
      in microplankton phenology changes and decreased trophic transfer efficiency.
AB  - We studied the effects of future climate change scenarios on plankton communities
      of a Norwegian fjord using a mesocosm approach. After the spring bloom, natural
      plankton were enclosed and treated in duplicates with inorganic nutrients
      elevated to pre-bloom conditions (N, P, Si; eutrophication), lowering of 0.4 pH
      units (acidification), and rising 3 degrees C temperature (warming). All nutrient
      amended treatments resulted in phytoplankton blooms dominated by chain-forming
      diatoms, and reached 13-16 MUg chlorophyll (chl) a l-1. In the control mesocosms,
      chl a remained below 1 MUg l-1. Acidification and warming had contrasting effects
      on the phenology and bloom-dynamics of autotrophic and heterotrophic
      microplankton. Bacillariophyceae, prymnesiophyceae, cryptophyta, and
      Protoperidinium spp. peaked earlier at higher temperature and lower pH.
      Chlorophyta showed lower peak abundances with acidification, but higher peak
      abundances with increased temperature. The peak magnitude of autotrophic
      dinophyceae and ciliates was, on the other hand, lowered with combined warming
      and acidification. Over time, the plankton communities shifted from autotrophic
      phytoplankton blooms to a more heterotrophic system in all mesocosms, especially
      in the control unaltered mesocosms. The development of mass balance and
      proportion of heterotrophic/autotrophic biomass predict a shift towards a more
      autotrophic community and less-efficient food web transfer when temperature,
      nutrients and acidification are combined in a future climate-change scenario. We
      suggest that this result may be related to a lower food quality for
      microzooplankton under acidification and warming scenarios and to an increase of
      catabolic processes compared to anabolic ones at higher temperatures. 

PMID- 24721995
TI  - Vibrational nano-spectroscopic imaging correlating structure with intermolecular
      coupling and dynamics.
AB  - Molecular self-assembly, the function of biomembranes and the performance of
      organic solar cells rely on nanoscale molecular interactions. Understanding and
      control of such materials have been impeded by difficulties in imaging their
      properties with the desired nanometre spatial resolution, attomolar sensitivity
      and intermolecular spectroscopic specificity. Here we implement vibrational
      scattering-scanning near-field optical microscopy with high spectral precision to
      investigate the structure-function relationship in nano-phase separated block
      copolymers. A vibrational resonance is used as a sensitive reporter of the local
      chemical environment and we image, with few nanometre spatial resolution and 0.2
      cm(-1) spectral precision, solvatochromic Stark shifts and line broadening
      correlated with molecular-scale morphologies. We discriminate local variations in
      electric fields between nano-domains with quantitative agreement with dielectric
      continuum models. This ability to directly resolve nanoscale morphology and
      associated intermolecular interactions can form a basis for the systematic
      control of functionality in multicomponent soft matter systems.

PMID- 24721994
TI  - Magnesium and embryonic development.
AB  - Important for energy metabolism, neurotransmission, bone stability, and other
      cellular functions, Mg(2+) has well-established and undisputedly critical roles
      in adult tissues. Its contributions to early embryonic development are less
      clearly understood. For decades it has been known that gestational Mg(2+)
      deficiency in rodents produces teratogenic effects. More recent studies have
      linked deficiency in this vital cation to birth defects in humans, including
      spina bifida, a neural fold closure defect in humans that occurs at an average
      rate of 1 per 1000 pregnancies. The first suggestion that Mg(2+) may be playing a
      more specific role in early development arose from studies of the TRPM7 and TRPM6
      ion channels. TRPM7 and TRPM6 are divalent-selective ion channels in possession
      of their own kinase domains that have been implicated in the control of Mg(2+)
      homeostasis in vertebrates. Disruption of the functions of these ion channels in
      mice as well as in frogs interferes with gastrulation, a pivotal process during
      early embryonic development that executes the emergence of the body plan and
      closure of the neural tube. Surprisingly, gastrulation defects produced by
      depletion of TRPM7 can be prevented by Mg(2+) supplementation, indicating an
      essential role for Mg(2+) in gastrulation and neural fold closure. The aim of
      this review is to summarize the data emerging from molecular genetic, biochemical
      and electrophysiological studies of TRPM6 and TRPM7 and provide a model of how
      Mg(2+), through these unique channel-kinases, may be impacting early embryonic
      development. 

PMID- 24721996
TI  - Celecoxib suppresses hepatoma stemness and progression by up-regulating PTEN.
AB  - Celecoxib, a COX-2 inhibitor and non-steroidal anti-inflammatory drug, can
      prevent several types of cancer, including hepatocellular carcinoma (HCC). Here
      we show that celecoxib suppressed the self-renewal and drug-pumping functions in
      HCC cells. Besides, celecoxib depleted CD44+/CD133+ hepatic cancer stem cells
      (hCSC). Prostaglandin E2 (PGE2) and CD133 overexpression did not reverse the
      celecoxib-induced depletion of hCSC. Also, celecoxib inhibited progression of rat
      Novikoff hepatoma. Moreover, a 60-day celecoxib program increased the survival
      rate of rats with hepatoma. Histological analysis revealed that celecoxib therapy
      reduced the abundance of CD44+/CD133+ hCSCs in hepatoma tissues. Besides, the
      hCSCs depletion was associated with elevated apoptosis and blunted proliferation
      and angiogenesis in hepatoma. Celecoxib therapy activated peroxisome proliferator
      activated receptor gamma (PPARgamma) and up-regulated PTEN, thereby inhibiting
      Akt and disrupting hCSC expansion. PTEN gene delivery by adenovirus reduced
      CD44/CD133 expression in vitro and hepatoma formation in vivo. This study
      suggests that celecoxib suppresses cancer stemness and progression of HCC via
      activation of PPARgamma/PTEN signaling. 

PMID- 24721997
TI  - Astral microtubule pivoting promotes their search for cortical anchor sites
      during mitosis in budding yeast.
AB  - Positioning of the mitotic spindle is crucial for proper cell division. In the
      budding yeast Saccharomyces cerevisiae, two mechanisms contribute to spindle
      positioning. In the Kar9 pathway, astral microtubules emanating from the daughter
      bound spindle pole body interact via the linker protein Kar9 with the myosin
      Myo2, which moves the microtubule along the actin cables towards the neck. In the
      dynein pathway, astral microtubules off-load dynein onto the cortical anchor
      protein Num1, which is followed by dynein pulling on the spindle. Yet, the
      mechanism by which microtubules target cortical anchor sites is unknown. Here we
      quantify the pivoting motion of astral microtubules around the spindle pole
      bodies, which occurs during spindle translocation towards the neck and through
      the neck. We show that this pivoting is largely driven by the Kar9 pathway. The
      microtubules emanating from the daughter-bound spindle pole body pivot faster
      than those at the mother-bound spindle pole body. The Kar9 pathway reduces the
      time needed for an astral microtubule inside the daughter cell to start pulling
      on the spindle. Thus, we propose a new role for microtubule pivoting: By pivoting
      around the spindle pole body, microtubules explore the space laterally, which
      helps them search for cortical anchor sites in the context of spindle positioning
      in budding yeast. 

PMID- 24721999
TI  - The use of a cell-free chondroinductive implant in a child with massive cartilage
      loss of the talus after an open fracture dislocation of the ankle: a case report.
AB  - BACKGROUND: We present a case report of a 3-year-old girl who sustained a severe
      open fracture dislocation of her talus with complete loss of full-thickness
      articular cartilage and subchondral bone over 80% of the talar dome. At
      presentation there was an extensive soft tissue defect including absent anterior
      joint capsule. She required a free anterolateral thigh flap to reconstruct this
      defect. The talar dome defect was treated with a cell-free chondroinductive
      implant made of resorbable polyglycolic acid felt and hyaluronic acid. This was
      the first use of such an implant in the United Kingdom and the first use in a
      child anywhere in the world. METHODS: The case has been followed prospectively
      for 3 years. RESULTS: At 3 years postoperative, the patient underwent thinning of
      the anterolateral thigh flap and trimming of an anterior tibial overgrowth, which
      was causing impingement. At surgery the talar dome cartilage looked pristine,
      with a line representing the tidemark between the original cartilage and the new
      formed. Biopsies were taken and histopathology performed. CONCLUSIONS: This was a
      rare and difficult case that has achieved an excellent outcome at this follow-up
      stage. LEVEL OF EVIDENCE: Level V.

PMID- 24722000
TI  - Do retained pediatric implants types impact later total hip arthroplasty?

PMID- 24722001
TI  - Canopy position affects the relationships between leaf respiration and associated
      traits in a tropical rainforest in Far North Queensland.
AB  - We explored the impact of canopy position on leaf respiration (R) and associated
      traits in tree and shrub species growing in a lowland tropical rainforest in Far
      North Queensland, Australia. The range of traits quantified included: leaf R in
      darkness (RD) and in the light (RL; estimated using the Kok method); the
      temperature (T)-sensitivity of RD; light-saturated photosynthesis (Asat); leaf
      dry mass per unit area (LMA); and concentrations of leaf nitrogen (N), phosphorus
      (P), soluble sugars and starch. We found that LMA, and area-based N, P, sugars
      and starch concentrations were all higher in sun-exposed/upper canopy leaves,
      compared with their shaded/lower canopy and deep-shade/understory counterparts;
      similarly, area-based rates of RD, RL and Asat (at 28  degrees C) were all higher
      in the upper canopy leaves, indicating higher metabolic capacity in the upper
      canopy. The extent to which light inhibited R did not differ significantly
      between upper and lower canopy leaves, with the overall average inhibition being
      32% across both canopy levels. Log-log RD-Asat relationships differed between
      upper and lower canopy leaves, with upper canopy leaves exhibiting higher rates
      of RD for a given Asat (both on an area and mass basis), as well as higher mass
      based rates of RD for a given [N] and [P]. Over the 25-45  degrees C range, the T
      sensitivity of RD was similar in upper and lower canopy leaves, with both canopy
      positions exhibiting Q10 values near 2.0 (i.e., doubling for every 10  degrees C
      rise in T) and Tmax values near 60  degrees C (i.e., T where RD reached maximal
      values). Thus, while rates of RD at 28  degrees C decreased with increasing depth
      in the canopy, the T-dependence of RD remained constant; these findings have
      important implications for vegetation-climate models that seek to predict carbon
      fluxes between tropical lowland rainforests and the atmosphere. 

PMID- 24722002
TI  - Parasites as biological tags in marine fisheries research: European Atlantic
      waters.
AB  - Studies of the use of parasites as biological tags for stock identification and
      to follow migrations of marine fish, mammals and invertebrates in European
      Atlantic waters are critically reviewed and evaluated. The region covered
      includes the North, Baltic, Barents and White Seas plus Icelandic waters, but
      excludes the Mediterranean and Black Seas. Each fish species or ecological group
      of species is treated separately. More parasite tag studies have been carried out
      on Atlantic herring Clupea harengus than on any other species, while cod Gadus
      morhua have also been the subject of many studies. Other species that have been
      the subjects of more than one study are: blue whiting Micromesistius poutassou,
      whiting Merlangius merlangus, haddock Melanogrammus aeglefinus, Norway pout
      Trisopterus esmarkii, horse mackerel Trachurus trachurus and mackerel Scomber
      scombrus. Other species are dealt with under the general headings redfishes,
      flatfish, tunas, anadromous fish, elasmobranchs, marine mammals and
      invertebrates. A final section highlights how parasites can be, and have been,
      misused as biological tags, and how this can be avoided. It also reviews recent
      developments in methodology and parasite genetics, considers the potential
      effects of climate change on the distributions of both hosts and parasites, and
      suggests host-parasite systems that should reward further research.

PMID- 24722004
TI  - Perioperative implications of the patient with autonomic dysfunction.
AB  - PURPOSE OF REVIEW: The autonomic nervous system functions to control heart rate,
      blood pressure, respiratory rate, gastrointestinal motility, hormone release, and
      body temperature on a second-to-second basis. Here we summarize some of the
      latest literature on autonomic dysfunction, focusing primarily on the
      perioperative implications. RECENT FINDINGS: The variety of autonomic dysfunction
      now extends to a large number of clinical conditions in which the cause or effect
      of the autonomic component is blurred. Methods for detecting dysautonomia can be
      as simple as performing a history and physical examination that includes
      orthostatic vital signs measured in both recumbent and vertical positions;
      however, specialized laboratories are required for definitive diagnosis. Heart
      rate variability monitoring is becoming more commonplace in the assessment and
      understanding of autonomic instability. Degenerative diseases of the autonomic
      nervous system include Parkinson's disease and multiple system atrophy, with the
      most serious manifestations being postural hypotension and paradoxical supine
      hypertension. Other conditions occur in which the autonomic dysfunction is only
      part of a larger disease process, such as diabetic autonomic neuropathy,
      traumatic brain injury, and spinal cord injury. SUMMARY: Patients with
      dysautonomia often have unpredictable and paradoxical physiological responses to
      various perioperative stimuli. Knowledge of the underlying pathophysiology of
      their condition is required in order to reduce symptom exacerbation and limit
      morbidity and mortality during the perioperative period.

PMID- 24722003
TI  - Analysis, optimization and verification of Illumina-generated 16S rRNA gene
      amplicon surveys.
AB  - The exploration of microbial communities by sequencing 16S rRNA genes has
      expanded with low-cost, high-throughput sequencing instruments. Illumina-based
      16S rRNA gene sequencing has recently gained popularity over 454 pyrosequencing
      due to its lower costs, higher accuracy and greater throughput. Although recent
      reports suggest that Illumina and 454 pyrosequencing provide similar beta
      diversity measures, it remains to be demonstrated that pre-existing 454
      pyrosequencing workflows can transfer directly from 454 to Illumina MiSeq
      sequencing by simply changing the sequencing adapters of the primers. In this
      study, we modified 454 pyrosequencing primers targeting the V4-V5 hyper-variable
      regions of the 16S rRNA gene to be compatible with Illumina sequencers. Microbial
      communities from cows, humans, leeches, mice, sewage, and termites and a mock
      community were analyzed by 454 and MiSeq sequencing of the V4-V5 region and MiSeq
      sequencing of the V4 region. Our analysis revealed that reference-based OTU
      clustering alone introduced biases compared to de novo clustering, preventing
      certain taxa from being observed in some samples. Based on this we devised and
      recommend an analysis pipeline that includes read merging, contaminant filtering,
      and reference-based clustering followed by de novo OTU clustering, which produces
      diversity measures consistent with de novo OTU clustering analysis. Low levels of
      dataset contamination with Illumina sequencing were discovered that could affect
      analyses that require highly sensitive approaches. While moving to Illumina-based
      sequencing platforms promises to provide deeper insights into the breadth and
      function of microbial diversity, our results show that care must be taken to
      ensure that sequencing and processing artifacts do not obscure true microbial
      diversity. 

PMID- 24722005
TI  - Postoperative nausea and vomiting in pediatric anesthesia.
AB  - PURPOSE OF REVIEW: Postoperative nausea and vomiting (PONV) has a high incidence
      in children and requires prophylactic and therapeutic strategies. RECENT
      FINDINGS: PONV can be reduced by the avoidance of nitrous oxide, volatile
      anesthetics, and the reduction of postoperative opioids. The use of
      dexamethasone, 5-HT3 antagonists, or droperidol alone is potent, but combinations
      are even more effective to reduce PONV. Droperidol has a Food and Drug
      Administration warning. Hence, dexamethasone and 5-HT3 antagonists should be
      preferred as prophylactic drugs. It is further reasonable to adapt PONV
      prophylaxis to different risk levels. Prolonged surgery time, inpatients, types
      of surgery (e.g. strabismus and ear-nose-throat surgery), and patients with PONV
      in history should be treated as high risk, whereas short procedures and
      outpatients are to be treated as low risk. SUMMARY: Concluding from the existing
      guidelines and data on the handling of PONV in children at least 3 years, the
      following recommendations are given: outpatients undergoing small procedures
      should receive a single prophylaxis, outpatients at high risk a double
      prophylaxis, inpatients with surgery time of more than 30 min and use of
      postoperative opioids should get double prophylaxis, and inpatients receiving a
      high-risk surgical procedure or with other risk factors a triple prophylaxis (two
      drugs and total intravenous anesthesia). Dimenhydrinate can be used as a second
      choice, whereas droperidol and metoclopramide can only be recommended as rescue
      therapy.

PMID- 24722006
TI  - Anesthesia and ventilation strategies in children with asthma: part I -
      preoperative assessment.
AB  - PURPOSE OF REVIEW: Asthma is a common disease in the pediatric population, and
      anesthetists are increasingly confronted with asthmatic children undergoing
      elective surgery. This first of this two-part review provides a brief overview of
      the current knowledge on the underlying physiology and pathophysiology of asthma
      and focuses on the preoperative assessment and management in children with
      asthma. This also includes preoperative strategies to optimize lung function of
      asthmatic children undergoing surgery. The second part of this review focuses on
      the immediate perioperative anesthetic management including ventilation
      strategies. RECENT FINDINGS: Multiple observational trials assessing
      perioperative respiratory adverse events in healthy and asthmatic children
      provide the basis for identifying risk factors in the patient's (family) history
      that aid the preoperative identification of at-risk children. Asthma treatment
      outside anesthesia is well founded on a large body of evidence. Optimization and
      to some extent intensifying asthma treatment can optimize lung function, reduce
      bronchial hyperreactivity, and minimize the risk of perioperative respiratory
      adverse events. SUMMARY: To minimize the considerable risk of perioperative
      respiratory adverse events in asthmatic children, a good understanding of the
      underlying physiology is vital. Furthermore, a thorough preoperative assessment
      to identify children who may benefit of an intensified medical treatment thereby
      minimizing airflow obstruction and bronchial hyperreactivity is the first pillar
      of a preventive perioperative management of asthmatic children. The second
      pillar, an individually adjusted anesthesia management aiming to reduce
      perioperative adverse events, is discussed in the second part of this review.

PMID- 24721998
TI  - Patterns of transmitted HIV drug resistance in Europe vary by risk group.
AB  - BACKGROUND: In Europe, a continuous programme (SPREAD) has been in place for ten
      years to study transmission of drug resistant HIV. We analysed time trends of
      transmitted drug resistance mutations (TDRM) in relation to the risk behaviour
      reported. METHODS: HIV-1 patients newly diagnosed in 27 countries from 2002
      through 2007 were included. Inclusion was representative for risk group and
      geographical distribution in the participating countries in Europe. Trends over
      time were calculated by logistic regression. RESULTS: From the 4317 patients
      included, the majority was men-having-sex-with-men -MSM (2084, 48%), followed by
      heterosexuals (1501, 35%) and injection drug users (IDU) (355, 8%). MSM were more
      often from Western Europe origin, infected with subtype B virus, and recently
      infected (<1 year) (p<0.001). The prevalence of TDRM was highest in MSM
      (prevalence of 11.1%), followed by heterosexuals (6.6%) and IDU (5.1%, p<0.001).
      TDRM was predominantly ascribed to nucleoside reverse transcriptase inhibitors
      (NRTI) with a prevalence of 6.6% in MSM, 3.3% in heterosexuals and 2.0% in IDU (p
      = 0.001). A significant increase in resistance to non- nucleoside reverse
      transcriptase inhibitors (NNRTIs) and a decrease in resistance to protease
      inhibitors was observed in MSM (p = 0.008 and p = 0.006, respectively), but not
      in heterosexual patients (p = 0.68 and p = 0.14, respectively). CONCLUSIONS: MSM
      showed to have significantly higher TDRM prevalence compared to heterosexuals and
      IDU. The increasing NNRTI resistance in MSM is likely to negatively influence the
      therapy response of first-line therapy, as most include NNRTI drugs.

PMID- 24722007
TI  - The micropatterning of layers of colloidal quantum dots with inorganic ligands
      using selective wet etching.
AB  - The micropatterning of layers of colloidal quantum dots (QDs) stabilized by
      inorganic ligands is demonstrated using PbS core and CdSe/CdS core/shell QDs. A
      layer-by-layer approach is used to assemble the QD films, where each cycle
      involves the deposition of a QD layer by dip-coating, and the replacement of the
      native organic ligands by inorganic moieties, such as OH(-) and S(2-), followed
      by a thorough cleaning of the resulting film. This results in a smooth and crack
      free QD film on which a photoresist can be spun. The micropatterns are defined by
      a positive photoresist, followed by the removal of uncovered QDs by selective wet
      etching with an HCl/H3PO4 mixture. The resulting patterns can have submicron
      feature dimensions, limited by the resolution of the lithographic process, and
      can be formed on planar and 3D substrates. It is shown that the photolithography
      and wet etching steps have little effect on the photoluminescence quantum yield
      of CdSe/CdS QDs. Compared with the unpatterned CdSe/CdS QD film, only a 10%
      degradation in the quantum yield is observed. These results demonstrate the
      feasibility of the proposed micropatterning method to implement the large-scale
      device integration of colloidal quantum dots. 

PMID- 24722008
TI  - Population-attributable causes of cancer in Korea: obesity and physical
      inactivity.
AB  - BACKGROUND: Changes in lifestyle including obesity epidemic and reduced physical
      activity influenced greatly to increase the cancer burden in Korea. The purpose
      of the current study was to perform a systematic assessment of cancers
      attributable to obesity and physical inactivity in Korea. METHODOLOGY/PRINCIPAL
      FINDINGS: Gender- and cancer site-specific population-attributable fractions
      (PAF) were estimated using the prevalence of overweight and obesity in 1992-1995
      from a large-scale prospective cohort study, the prevalence of low physical
      activity in 1989 from a Korean National Health Examination Survey, and pooled
      relative risk estimates from Korean epidemiological studies. The overall PAF was
      then estimated using 2009 national cancer incidence data from the Korea Central
      Cancer Registry. Excess body weight was responsible for 1,444 (1.5%) and 2,004
      (2.2%) cancer cases among men and women, respectively, in 2009 in Korea. Among
      men, 6.8% of colorectal, 2.9% of pancreatic, and 16.0% of kidney cancer was
      attributable to excess body weight. In women, 6.6% of colorectal, 3.9% of
      pancreatic, 18.7% of kidney, 8.2% of postmenopausal breast, and 32.7% of
      endometrial cancer was attributable to excess body weight. Low leisure-time
      physical activity accounted for 8.8% of breast cancer, whereas the PAF for
      overall cancer was low (0.1% in men, 1.4% in women). Projections suggest that
      cancers attributable to obesity will increase by 40% in men and 16% in women by
      2020. CONCLUSIONS/SIGNIFICANCE: With a significantly increasing overweight and
      physically inactive population, and increasing incidence of breast and colorectal
      cancers, Korea faces a large cancer burden attributable to these risk factors.
      Had the obese population of Korea remained stable, a large portion of obesity
      related cancers could have been avoided. Efficient cancer prevention programs
      that aim to reduce obesity- and physical inactivity-related health problems are
      essential in Korea.

PMID- 24722009
TI  - Semitendinosus Tendon Autograft for Reconstruction of Large Defects in Chronic
      Achilles Tendon Ruptures.
AB  - BACKGROUND: Chronic Achilles tendon ruptures are associated with considerable
      functional morbidity. When treated operatively, debridement of degenerated tendon
      ends may create large defects. Various procedures to reconstruct large defects
      have been described. We present a simple technique in which an autologous
      semitendinosus tendon graft is used to reconstruct defects larger than 5 cm in
      chronic Achilles tendon ruptures. The purpose of this study was to describe our
      operative technique and its functional outcome. METHODS: Achilles ruptures of
      more than 6 weeks duration were considered for the study. We treated 35 patients
      (20 males, 15 females) with symptomatic chronic Achilles tendon ruptures. The
      mean age was 47.4 years (range, 30 to 59). The smallest defect that we had
      reconstructed was 5 cm, and the largest was 9 cm in length. The average follow-up
      duration was 30.7 months (range, 20 to 42). Postoperatively, the strength of
      gastrocsoleus was measured by manual muscle testing (MMT) in non-weight-bearing
      and weight-bearing positions. RESULTS: All operated patients showed satisfactory
      functional outcome, good soft tissue healing, and no reruptures. The preoperative
      weight-bearing MMT of 2/5 improved to 4/5 or 5/5 postoperatively. In all
      patients, postoperative non-weight-bearing MMT was 5/5. All patients returned to
      their prerupture daily activity. CONCLUSION: We present a technique that is
      simple, with low morbidity. We believe it is a valuable option especially when
      allografts are not available. It is inexpensive as suture anchors or tenodesis
      screws are not used. This can be a useful option if other tendons (flexor
      hallucis longus, peroneus brevis, etc) are not available for transfer. LEVEL OF
      EVIDENCE: Level IV, retrospective case series.

PMID- 24722011
TI  - Do the clinical diagnostic skills of dermatologists correlate with the
      histopathological gold standard?

PMID- 24722010
TI  - Mass spectrometry-based analysis of glycoproteins and its clinical applications
      in cancer biomarker discovery.
AB  - Glycosylation is one of the most important posttranslational modifications of
      proteins and plays essential roles in various biological processes. Aberration in
      the glycan moieties of glycoproteins is associated with many diseases. It is
      especially critical to develop the rapid and sensitive methods for analysis of
      aberrant glycoproteins associated with diseases. Mass spectrometry (MS) has
      become a powerful tool for glycoprotein analysis. Especially, tandem mass
      spectrometry can provide highly informative fragments for structural
      identification of glycoproteins. This review provides an overview of the
      development of MS technologies and their applications in identification of
      abnormal glycoproteins and glycans in human serum to screen cancer biomarkers in
      recent years. 

PMID- 24722013
TI  - Ultrasound-guided caudal epidural injection technique.

PMID- 24722012
TI  - Upstream Transcription Factor 1 (USF1) allelic variants regulate lipoprotein
      metabolism in women and USF1 expression in atherosclerotic plaque.
AB  - Upstream transcription factor 1 (USF1) allelic variants significantly influence
      future risk of cardiovascular disease and overall mortality in females. We
      investigated sex-specific effects of USF1 gene allelic variants on serum indices
      of lipoprotein metabolism, early markers of asymptomatic atherosclerosis and
      their changes during six years of follow-up. In addition, we investigated the cis
      regulatory role of these USF1 variants in artery wall tissues in Caucasians. In
      the Cardiovascular Risk in Young Finns Study, 1,608 participants (56% women, aged
      31.9 +/- 4.9) with lipids and cIMT data were included. For functional study,
      whole genome mRNA expression profiling was performed in 91 histologically
      classified atherosclerotic samples. In females, serum total, LDL cholesterol and
      apoB levels increased gradually according to USF1 rs2516839 genotypes TT < CT <
      CC and rs1556259 AA < AG < GG as well as according to USF1 H3 (GCCCGG) copy
      number 0 < 1 < 2. Furthermore, the carriers of minor alleles of rs2516839 (C) and
      rs1556259 (G) of USF1 gene had decreased USF1 expression in atherosclerotic
      plaques (P = 0.028 and 0.08, respectively) as compared to non-carriers. The
      genetic variation in USF1 influence USF1 transcript expression in advanced
      atherosclerosis and regulates levels and metabolism of circulating apoB and apoB
      containing lipoprotein particles in sex-dependent manner, but is not a major
      determinant of early markers of atherosclerosis. 

PMID- 24722014
TI  - Use of long term molecular dynamics simulation in predicting cancer associated
      SNPs.
AB  - Computational prediction of cancer associated SNPs from the large pool of SNP
      dataset is now being used as a tool for detecting the probable oncogenes, which
      are further examined in the wet lab experiments. The lack in prediction accuracy
      has been a major hurdle in relying on the computational results obtained by
      implementing multiple tools, platforms and algorithms for cancer associated SNP
      prediction. Our result obtained from the initial computational compilations
      suggests the strong chance of Aurora-A G325W mutation (rs11539196) to cause
      hepatocellular carcinoma. The implementation of molecular dynamics simulation
      (MDS) approaches has significantly aided in raising the prediction accuracy of
      these results, but measuring the difference in the convergence time of mutant
      protein structures has been a challenging task while setting the simulation
      timescale. The convergence time of most of the protein structures may vary from
      10 ns to 100 ns or more, depending upon its size. Thus, in this work we have
      implemented 200 ns of MDS to aid the final results obtained from computational
      SNP prediction technique. The MDS results have significantly explained the atomic
      alteration related with the mutant protein and are useful in elaborating the
      change in structural conformations coupled with the computationally predicted
      cancer associated mutation. With further advancements in the computational
      techniques, it will become much easier to predict such mutations with higher
      accuracy level. 

PMID- 24722015
TI  - [Comparative assessment of antiaggregant efficacy of acetylsalicylic acid and
      clopidogrel in peripheral atherosclerosis].
AB  - Presented in the article are the results of studying antiaggregate activity of
      acetylsalicylic acid and clopidogrel in a total of 36 patients suffering from
      various-severity chronic arterial insufficiency of lower limbs on the background
      of atherosclerosis obliterans. The study was conducted prior to treatment for
      correct selection of a particular antiplatelet agent. The obtained results showed
      that clopidogrel was not always more efficient than acetylsalicylic acid, since
      there is individual sensitivity of each patients to a particular antiplatelet
      agent. Therefore, an individual approach is necessary to conservative therapy of
      arterial insufficiency of lower limbs. For some patients it is preferable to
      administer clopidogrel, for others - acetylsalicylic acid. In a series of cases
      combined treatment is justified, while some patients having low sensitivity to
      both acetylsalicylic acid and clopidogrel require careful selection of
      alternative agents influencing other thrombocyte receptors. 

PMID- 24722016
TI  - [Has the era of warfarin terminated?].
AB  - Warfarin has for a long time been considered the "gold standard" of oral
      anticoagulant therapy. Positive effects of this agent are unambiguously supported
      by accumulated evidence-based data convincingly confirming a decrease in the risk
      for thrombolytic complications in patients with many diseases of the
      cardiovascular system: atrial fibrillation, thrombosis of deep veins of
      extremities, pulmonary artery thromboembolism. However, warfarin has a series of
      disadvantages complicating its practical application: the necessity of individual
      adjustment of the dose to maintain the International Normalized Ratio (INR)
      within the limits of the target values, clinically significant interactions with
      other drugs and foodstuffs. In this connection, the advent of new oral
      anticoagulants such as dabigatran, rivaroxaban, and apixaban is associated with
      great hopes concerning increased efficiency and safety of anticoagulant therapy.
      However, while the results of large-scale clinical trials are promising, the data
      on using these agents in real clinical practice suggest that prescription and
      administration of new oral anticoagulants should be approached with great
      caution, thoroughly weighing potential risks and benefits. Therefore, switching
      over the patients with the already adjusted dosage of warfarin and stable values
      of the INR to new drugs seems hardly advisable. 

PMID- 24722017
TI  - [Immunological aspects of formation of restenoses after endothelial lesions].
AB  - The article deals with an analysis of the literature data concerning
      immunological mechanisms of the formation of restenoses after damage of the
      arterial wall, considering the participants of the early and late phases of
      inflammatory response initiated by endothelial damage. Also given is
      characteristics of the process of formation on the neointima, followed by
      description of the role of intercellular adhesion molecules in initiation and
      maintaining of the processes of acute and chronic inflammation. 

PMID- 24722018
TI  - [System of microcirculation, markers of vascular wall damage and systematicity of
      the process in rheumatic diseases].
AB  - The work was aimed at studying the interrelationship of the microcirculation
      system and the parameters of endothelial activation with markers of inflammatory
      process activity in rheumatic diseases (RD). We carried out a comprehensive
      examination of a total of 330 patients presenting with systemic diseases of
      connective tissue (SDCT), rheumatoid arthritis (RA) and systemic vasculitis (SV).
      Studying microcirculation included impregnation of filmy preparations according
      to the V.V. Kupriyanov technique and biomicroscopy of the conjunctiva of the
      eyeball. We also determined markers of endothelial activation and lesion of
      vascular wall, indices of activity of rheumatoid arthritis (RA), systemic lupus
      erythematosus (SLE) and vasculitis clinical activity index (VCAI), common carotid
      artery intima-media thickness (CCA-IMT), biopsy materials of the musculocutaneous
      flap, of the operational and autopsy materials. Determining the indices of
      microcirculation showed that first of all the process involves postcapillaries
      and venules which are dilated, becoming tortuous, with the formation of
      microaneurysms and stellate venules. Capillaries, postcapillaries and venules
      were found to contain parietally located small-grained conglomerates of blood
      platelets and thrombocytic masses plugging up the lumens of microvessels.
      Intravascular alterations were characterized by the presence of erythrocyte
      aggregates, stases, microthrombovasculitis, "sludge" phenomenon, and a decrease
      in capillary blood flow. Extravascular changes included perivascular
      haemorrhages. In arterioles and precapillaries the inflammatory process
      manifested itself by swelling, dystrophy and desquamation of endothelial cells,
      plasmatic impregnation of the walls, luminal thrombosis followed by the
      development of severe sclerosis and glialinosis. The morphological study showed
      the presence of destructive alterations in the vascular wall, fibrinoid necrosis,
      and infiltration-proliferative cellular reaction. The most pronounced changes in
      the autoimmune inflammation markers had place in RA and systemic lupus
      erythematosus (SLE). We revealed increased indices of inflammatory process
      activity such as interleukin-8, C-reactive protein (CRP). We also revealed the
      signs of endothelial dysfunction, manifesting itself as a statistically
      significant (p<0.01) increase in concentrations of the soluble vascular cell
      adhesion molecule (sVCAM-1), von Willebrand factor antigen (VWFA), the number of
      desquamated endotheliocytes (DE). Also observed was a clear-cut dependence of the
      level of endothelial activation markers from the degree of the processes
      activity. We revealed a positive correlation between the level of CRP, IgG RF,
      the level of sVCAM-1 and the number of DE. The levels of interleukin-8, sVCAM-1
      and VWFA were elevated in patients with RD. Increased activity of the disease was
      accompanied by impairments at the level of the microcirculatory bed, an increase
      in the concentration of inflammation markers and indices of endothelial
      dysfunction. 

PMID- 24722019
TI  - [Cardiosynchronized sequential antegrade pneumocompression in treatment of
      patients with multifocal atherosclerosis].
AB  - The work was aimed at assessing efficacy and safety of indications for and
      contraindications to a promising method of treatment for multifocal
      atherosclerosis - enforced external counterpulsation, suggesting a new
      noninvasive method of treatment of chronic obliterating diseases of lower-limb
      arteries - cardiosynchronized sequential antegrade pneumocompression. 

PMID- 24722020
TI  - [Ultrasonic doppler flowmetry in intraoperative diagnosis of coronary bypass
      grafts incompetence].
AB  - According to the findings of many authors, occlusion of bypass grafts may develop
      as early as during surgery in 4-12% of patients. At discharge from hospital this
      index may reach 5-20%, increasing to 30% within the first year. Incompetence of
      bypass grafts is in many cases a consequence of errors in surgical technique and
      may therefore be decreased by means of improving the control over quality of
      coronary bypass grafting. Using the method of ultrasound Doppler flowmetry in the
      conditions of artificial circulation and clamped artery, we assessed a total of
      64 composite bypass grafts. Blood flow was assessed by such parameters as the
      pulsatility index (PI), mean volumetric blood flow velocity (Qmean), and
      percentage of diastolic volumetric filling (DF). The obtained results were
      statistically processed. The mean values of blood flow parameters were obtained,
      followed by determining dependence between peripheral resistance (PI) prior to
      removal of the clamp from the aorta and peripheral resistance (PI) measured after
      termination of extracorporeal circulation. 

PMID- 24722021
TI  - The role of endovascular therapy in the treatment of critical limb ischemia.
AB  - The article deals with advantages and unsolved problems of endovascular treatment
      in patients with lower limb peripheral arterial disease (PAD). This is
      accompanied by a brief excursion into historical domain, pointing out a
      staggering increase in the number of endovascular interventions. At the same
      time, it is noted that the strength of the evidence-based data contained in the
      currently available literature supporting long-term efficacy of endovascular
      therapy for lower extremity occlusive disease is weak, and hence there are no
      undisputable advantages of this therapeutic modality over open surgical
      interventions. In conclusion, it is underlined that the choice of therapy offered
      to a given patient should be individualized to each encountered clinical
      situation, taking into account the well-known benefits and shortcomings of both
      treatment strategies. 

PMID- 24722022
TI  - Early experience with the DJUMBODIS system: what did we observed, what can we
      expect? Part 2.
AB  - The authors describe their experience with the Djumbodis system, reporting the
      findings of a comparative study focussing on the outcomes of surgical management
      of patients presenting with real type I aortic dissection. The most common
      feature observed in patients receiving a 9 or 14 cm stent into the proximal
      descending aorta was stabilization of the dissected thoracic segments. Clinical
      outcomes were, however, comparable between the groups of stented patients and
      controls. This clinical result is to be shared with other endovascular devices
      used in acute dissections and which might require a hybrid operating room, since
      they might compromise blood flow in collateral arteries. Carefully analysing our
      data and current literature we propose to consider real type I aortic dissections
      complicated by dynamic malperfusion symptoms or for which the diameter of the
      proximal descending aorta is already noticeably dilated as justified indications
      according to the current knowledge about stenting of acute dissections. 

PMID- 24722023
TI  - [Use of balloon-expandable stent graft for treatment of a false pseudoaneurysm of
      the proximal anastomosis of the iliac-femoral bypass graft].
AB  - The authors present in the article a case report of successful use of a balloon
      expandable stent graft for endovascular prosthetic reconstruction of an aneurysm
      of the proximal anastomosis of the iliac-femoral bypass graft by puncture
      approach through the brachial artery. We implanted a balloon-expandable stent
      graft measuring 6.0-12.0 mm in diameter and 58-mm long with good immediate and
      short-term results in the anastomosis with large alteration in the diameter along
      the length. 

PMID- 24722024
TI  - [Endovascular closure of iatrogenic arteriovenous anastomosis of the iliac artery
      and vein].
AB  - The presented herein clinical case report concerns successful endovascular
      closure of a iatrogenic lesion of the iliac artery and inferior vena cava with
      formation of a pathological arteriovenous anastomosis manifesting itself by
      venous thromboembolic syndrome and severe right-ventricular insufficiency. 

PMID- 24722026
TI  - [Use of laser technologies in treatment of chronic venous insufficiency in
      patients with a wide ostial segment of the main trunks of subcutaneous veins].
AB  - Presented herein is the authors' experience in endovascular laser obliteration of
      the major trunks of the grate saphenous vein (GSV) with a wide ostial segment
      (measuring from 15 to 34 mm) in patients presenting with chronic venous
      insufficiency. Group One patients (n=32) underwent crossectomy followed by
      endovasal laser obliteration (EVLO) of the GSV's trunk on the femur. Group Two
      patients (n=46) were not subjected to crossectomy, whereas obliteration of the
      GSV's trunk was carried out immediately from the ostium. In Group One we managed
      to achieve obliteration of the GSV's trunk in 32 patients (100%) with no
      additional interventions, and in Group Two this was achieved in 42 (91.3%)
      patients. Four patients (8.7%) required performing a secondary procedure of EVLO
      after which obliteration of the trunk was achieved in all patients of Group Two.
      There was no evidence of deep-vein thrombosis. 

PMID- 24722025
TI  - [Analysis of efficacy of radiofrequency obliteration with due regard for the
      target vein's diameter].
AB  - AIM: Data concerning the effect of the target vein's diameter on efficacy of
      radiofrequency obliteration (RFO) in the current literature are limited. AIM: To
      assess efficacy of RFO and stripping, peculiarities of the postoperative period
      course with due regard for the diameter of the target veins, to compare the
      outcomes of RFO and classical phlebectomy in treatment of varicose disease during
      1-year follow up by a composite end point. MATERIAL AND METHODS: A multicenter
      prospective non-randomized study based on analysing therapeutic outcomes in a
      total of 218 patients presenting with varicose disease (C2-C3 according to the
      CEAP). RFO was performed in 108 patients and phlebectomy in 110 subjects. The
      results were assessed by means of a composite end point including four
      components: technical outcome at 1-year follow-up, pain, subcutaneous
      haemorrhage, and paresthesias. The groups of patients who endured RFO and
      phlebectomy were subdivided into two subgroups according to the target vein's
      diameter with a border of 14 mm. Statistical analysis. We used the methods of non
      parametric statistics (contingency tables, chi squared test), calculating the
      odds ratio (OR) for a favourable outcome with a 95% confidential interval. Pain
      dynamics was assessed by means of intellectual data analysis (cluster analysis).
      RESULTS: "Phelbectomy >= 14 mm" and "RFO >= 14 mm". The incidence rate of a good
      outcome in the subgroups amounted to 20 (30.8%) and 61 (95.3%), respectively. The
      odds ratio for favourable outcome between the subgroups of RFA and phlebectomy
      amounted to 45.8; 95% CI (44.5-47.0). "RFA >= 14 mm" and "RFA < 14 mm".
      Favourable outcome rate in the subgroups amounted to 25 (39.1%) and 17 (38.6%),
      respectively. The differences were not statistically significant, p=0.24. The
      odds ratio for a good outcome between the RFO subgroups amounted to: OR=0.98; 95%
      CI (0.18-1.77). Comparative analysis of RFO outcomes between the clinics.
      Favourable outcome rate in the first clinic was 50 (92.6%), in the second 34
      (87.2%), and in the third 13 (86.6%), with the difference being statistically
      insignificant, p=0.7. The cluster analysis of the pain dynamics after the
      intervention. The clusters with moderate pain were composed of the patients after
      phlebectomy. These clusters showed association of pain intensity with increased
      BMI and greater vein diameter. CONCLUSION: 1) RFA of great-diameter veins by a
      favourable outcome by the composite end point (CED) turned out to be superior to
      the classic phlebectomy. 2) For RFA the incidence rate of a favourable outcome by
      the CED does not depend on the target vein's diameter. 3) A pronounced pain
      syndrome after phlebectomy was associated with excessive body weight or obesity
      and greater diameter of the vein.

PMID- 24722027
TI  - [Comparative analysis of quality of life of patients in the early and remote
      periods of iliofemoral phlebothrombosis].
AB  - The authors present in the article the results of studying quality of life of
      patients at various terms after endured iliofemoral phlebothrombosis (from 0 to
      60 months), who, depending upon embologenicity of the thrombus in order to
      prevent pulmonary embolism, were either subjected to implantation of a cava
      filter or not. The patients were subdivided into two groups: the study group (129
      subjects) included those presenting with acute or recently endured iliofemoral
      phlebothrombosis and a cava filter implanted at various time having elapsed
      after. The comparison group consisted of 96 patients with endured iliofemoral
      phlebothrombosis within the same terms and having received conservative treatment
      without implantation of a cava filter. Quality of life was assessed by two
      questionnaires, i.e. MOS-SF-36 and CIVIQ. The authors concluded that the patients
      with endured iliofemoral phlebothrombosis without implantation of a cava filter
      in the anamnesis demonstrated slightly better measures of quality of life. 

PMID- 24722028
TI  - [Stages of development of surgical treatment for insufficiency of venous valves
      of lower limbs].
AB  - Insufficiency of the valvular apparatus of the lower-limb veins is one of the
      main causes of the development of chronic venous insufficiency. This disease is
      commonly prevalent in developed countries including Russia and is an urgent and
      socially significant problem. Insufficiency of the venous valves may be corrected
      by a wide variety of approaches and methods however they all are not universal or
      have low efficacy and in some cases cannot be applied at all. This article is
      dedicated to the review of the existing methods of surgical correction of
      valvular insufficiency of lower-limb veins, as well as a review of the studies of
      the most promising trend of this problem, i.e. prosthetic repair of venous
      valves. 

PMID- 24722030
TI  - [Immediate results of surgical reconstruction of the aortic arch in patients with
      proximal aortic dissection].
AB  - AIM: Despite obvious progress of surgical technologies in correction of proximal
      aortic pathology, improvement of methods of protection of the brain, one of the
      main problems of this direction remains the development of postoperative cerebral
      ischaemia of various degree of manifestation: strokes, transitory ischaemic
      attacks, or hypoxic encephalopathy. Of special interest is studying the group of
      patients presenting with aortic dissection, since this pathology may be
      accompanied by a wide variety of combinations of occlusive and stenotic lesions
      of the branches of the ascending portion of the aorta and aortic arch (coronary
      and brachiocephalic basins) by the detached intima. MATERIAL AND METHODS: Over
      the period from 1999 to 2011, we operated on a total of 124 patients presenting
      with DeBakey type I aortic dissection. Of these, 194 were men (75.8%) and 30
      (24.2%) women. The mean age amounted to 48.7+/-11.0 years. Etiologically
      prevailing were systemic atherosclerosis (91 patients, 73.4% of cases) and
      Marfan's syndrome in 14 (11.3%) cases. In all patients operative intervention
      included reconstruction of the aortic arch according to one of the following
      techniques: prosthetic repair according to the type of an aggressive oblique
      anastomosis ("hemiarch repair") - 78 (62.9%) patients, prosthetic repair of the
      aortic arch using the multiple-branch prosthesis Plexus Vascutek - 37 (29.8%)
      patients, and nine patients underwent prosthetic repair of the aortic arch with a
      vascular graft with reimplantation of the brachiocephalic arteries with a single
      islet. The average duration of artificial circulation amounted to 230.1+/-70.0
      minutes, the mean time of aortic occlusion was 167.2+/-44.2 minutes and that of
      circulatory arrest equalled 51.9+/-16.2 minutes. The brain during hypothermic
      circulatory arrest was protected according to the following techniques: 16
      (12.9%) patients - isolated hypothermia with no cerebral perfusion, 76 (61.3 %)
      patients retrograde cerebral perfusion (RCP) through the superior vena cava, 23
      (18.6%) patients - antegrade cerebral perfusion (ACP) and in 8 (6.5%) patients a
      combination of RCP + antegrade cerebral perfusion. CONCLUSION: The early
      postoperative period showed a clear-cut interrelationship between the aetiology
      of aortic dissection and the onset of impairment of cerebral circulation.
      Increased incidence of strokes is promoted by more complicated and hence longer
      in time types of reconstruction of the aortic arch (islet technique, multiple
      branch prosthesis). Antegrade cerebral perfusion had no statistically significant
      advantages over retrograde perfusion or perfusion-free hypothermic protection of
      the brain. Neither did the type of aortic dissection exert influence on cerebral
      circulation impairment (CCI). The presence of accompanying diseases did not
      determine the probability of the development of CCI in the early postoperative
      period. The analysis of the obtained findings revealed statistically significant
      relationship between the patient's age and severity of CCI.

PMID- 24722029
TI  - [Peculiarities of treatment policy for lower-limb phlebothromboses].
AB  - Quality of treatment for acute venous thrombosis is determined by adequacy of
      conservative treatment and optimization of the operative procedure. We analysed
      the outcomes of management of 1,768 patients presenting with various forms of
      lower-limb phlebothrombosis. Deep veins were affected in 1,158 (65.5%) cases. Of
      these, thrombosis of crural veins was revealed in 672 (58%) patients, iliofemoral
      phlebothrombosis in 486 (42%) subjects. A total of 47 (9.7%) patients were
      operated on for iliofemoral thrombosis with floating thrombus confirmed by
      ultrasonic angioscanning. Criteria for floatation were determined. A total of 610
      (43.5%) patients were diagnosed as having ascending subcutaneous thrombophlebitis
      of the femur. Of these, a total of 592 (97%) patients were operated on within 1
      48 hours following admission. We propose a methodology of comprehensive
      conservative treatment with the use of Antistax in a double dose and alternating
      pneumocompression with elevated pressure in the cuffs. 

PMID- 24722031
TI  - [Comparative assessment of immediate outcomes of surgical treatment of patients
      with coronary artery disease and lesion of the brachiocephalic arteries].
AB  - From 2000 to 2011, a total of 52 patients with combined atherosclerotic lesions
      of the coronary and brachiocephalic arteries were subjected to a single-stage
      operation. Depending on the type of operative intervention, all patients were
      subdivided into two groups: Group One comprising 13 patients who underwent
      coronary artery bypass grafting (CABG) in a combination with simultaneous
      stenting of the internal carotid artery, and Group Two consisting of 39 patients
      subjected to CABG with simultaneous carotid endarterectomy. Assessing the
      intraoperative parameters revealed that in Group One patients the average
      duration of operations was significantly lower (179.6+/-6.4 minutes versus
      273.2+/-5.6 minutes in Group Two, p<0.001) and the time of assisted circulation
      was less than in Group Two, averaging 75.9+/-4.5 versus 115.2+/-3.8 minutes,
      respectively (p<0.001). The duration of pulmonary artificial ventilation in Group
      One patients was less than in Group Two patients (9.7+/-2.6 hours versus 25+/-4.8
      hours, respectively, p< 0.01). Also the duration of staying in the critical care
      unit was shorter in Group One patients than in Group Two patients (21.5+/-3.3
      versus 82.1+/-8.0 hours, respectively, p<0.001). The overall hospital mortality
      rate amounted to 12.8% (5 patients), with all deaths having occurred in Group
      Two. The lethal outcomes were caused by acute myocardial infarction in three
      cases, one patient died of progressing multiple-organ failure on the background
      of acute impairment of cerebral circulation and one death was caused by
      thrombosis of the mesenteric artery with the development of intestinal gangrene
      and peritonitis. In the structure of hospital complications cardiac insufficiency
      was prevalent (23.1% and 59.0% for Groups One and Group Two patients,
      respectively, p<0.05). Analysing the incidence and structure of other
      postoperative complications revealed no statistically significant differences
      between the groups. Our study demonstrated that using surgical methods of
      treatment of patients with haemodynamically significant stenoses of the coronary
      and brachiocephalic arteries makes it possible to increase the overall survival
      rate in patients suffering this disease and to decrease the incidence rate of
      ischaemic impairments of the coronary and cerebral circulation. The hybrid method
      of treatment on arteries of various vascular basins may be an alternative to
      carotid endarterectomy and CABG, especially in patients running high surgical
      risk. 

PMID- 24722032
TI  - [Ways to improve patency of the femoral-popliteal-crural bypass grafts].
AB  - Chronic obliterating diseases of lower-limb arteries account for more than 20% of
      all manifestations of cardiovascular pathology. A surgical method of treatment
      for this pathology remains most effective. The types of operations below the
      inguinal fold currently used are as follows: bypass grafting, endarterectomy, and
      angioplasty. The vein is the material of choice and if it is not easily available
      allografts may be used. Differing elastic properties of the artery and prosthesis
      lead to progression of the neointima thus negatively affecting patency of bypass
      grafts. This article describes venous bypass grafts, their efficacy, methods of
      improving patency of allografts, as well as variants of combined operations. 

PMID- 24722033
TI  - [Postoperative wound complications in cardiosurgery].
AB  - Presented in the article are the results of examination and treatment of 65
      patients with infectious wound complications of the sternotomic injury after open
      heart surgery. The main risk factors for their development in our patients were
      as follows: obesity, chronic obstructive pulmonary disease, diabetes mellitus,
      severe heart failure, prolonged operation, sternal instability. The leading
      pathogenic microorganisms were Gram positive staphylococci. Treatment varied from
      prolonged antibiotic therapy with surgical debridement of the wound to subtotal
      resection of the sternum with various plastic reconstructive interventions. The
      scope of treatment was determined by the type and severity of infectious wound
      complications. Due to lack of standardized approaches in diagnosis, treatment and
      prevention this problem remains to be of current importance. 

PMID- 24722034
TI  - [Review of materials on vascular surgery presented at the Congress of the
      International Society of Surgery (Helsinki, Finland, August 25-29, 2013)].
AB  - The article contains a brief review of the materials concerning vascular surgery
      presented at the Congress of the International Society of Surgery held on August
      25-29, 2013 in Helsinki (Finland), showing the outcomes of open and endovascular
      operations performed in patients presenting with abdominal aortic aneurysms,
      lower-limb critical ischaemia, obtained in various clinics. This is followed by
      determining the prospects of further increasing efficiency of surgical methods of
      treatment of vascular diseases. 

PMID- 24722035
TI  - [Retrograde type A aortic dissection after endovascular repair of the thoracic
      artery].
AB  - Retrograde type A aortic dissection is a severe and prognostically unfavourable
      complication of endovascular repair of the thoracic aorta. The aim of the present
      article is to describe a clinical case report concerning a hybrid operative
      intervention for retrograde type A aortic dissection in a patient having endured
      two-stage endovascular repair of the thoracic artery. 

PMID- 24722036
TI  - [Treatment of reperfusion renal lesion after surgical management of chronic post
      embolic pulmonary hypertension by means of extracorporeal membrane oxygenation
      (ECMO)].
AB  - Thromboendarterectomy from the branches of the pulmonary artery is a
      conventionally accepted approach to treatment for pulmonary hypertension in
      chronic pulmonary embolism. A frequently encountered complication associated with
      this operation is the development in the postoperative period of the reperfusion
      syndrome as a potential cause of fatal respiratory failure. Taking into
      consideration that the reperfusion syndrome is a reversible process, waiting
      measures of support may save the patient's life. The present article deals with a
      case report concerning successive surgical management of a female patient
      suffering from chronic recurrent pulmonary thromboembolism accompanied by high
      pulmonary hypertension complicated by severe respiratory insufficiency in the
      early postoperative period, thus requiring long-term use of veno-venous
      extracorporeal membrane oxygenation (ECMO). The clinical case described in the
      article shows that veno-venous ECMO may be employed to save patients presenting
      with reperfusion syndrome following thromboendarterectomy from the branches of
      the pulmonary artery. The method of connecting ECMO namely in the veno-venous
      option in this particular case was determined by fact that the patient had no
      cardiac insufficiency. Numerous studies conducted hitherto have also confirmed
      that using ECMO in the veno-venous variant is accompanied and followed by a lower
      incidence rate of complications as compared with that of the veno-arterial
      variant. The results of our case report strongly suggest that timely use of ECMO
      in the composition of rehabilitation measures during restoration of the
      compromised lungs may become an effective strategy aimed at improving survival of
      patients after successful thromboendarterectomy from the pulmonary artery
      branches. 

PMID- 24722037
TI  - [Conservative treatment of patients with intermittent claudication].
AB  - The article deals with the analysis of the results of randomized placebo
      controlled studies of various therapeutic agents currently available in Russia,
      as well as the results of meta-analyses and Cochrane reviews of medicamentous
      treatment of patients with intermittent claudication. The results of these
      studies gave grounds to recommend the most efficient agents in the new edition of
      the "National Guidelines on management of patients with lower-limb arterial
      disease" (2013). 

PMID- 24722039
TI  - Ultrasound and magnetic resonance findings and correlation in hemiplegic patients
      with shoulder pain.
AB  - BACKGROUND: The aim of this study was to evaluate the ultrasonography (US) and
      MRI findings in hemiplegic patients with shoulder pain and investigate the
      correlation between them. It is not possible for these patients to fully perform
      active range of motion (ROM) and stress tests, so imaging methods take center
      stage in diagnosis and treatment planning. MATERIALS AND METHODS: A total of 68
      hemiplegic patients with shoulder pain attending the inpatient rehabilitation
      program were included in the study. MRI and US results from the patient files
      were recorded. The frequency of each pathology identified by US and MRI was
      determined. The distribution of MRI and US findings was investigated to see
      whether there was a statistical difference between the correlation of MRI and US
      results. RESULTS: The mean (SD) age of the patients was 63.7 (8.3) years and the
      mean (SD) duration of hemiplegia was 49 (8.9) days. According to the MRI results,
      glenohumeral and acromioclavicular joint degeneration was found in 77.9% and
      79.7% of the patients, respectively; subacromial-subdeltoid bursitis in 80.9%;
      fluid increase in the joint space in 41.2%; supraspinatus tendinitis in 36.8%;
      and supraspinatus partial rupture in 33.8%. Shoulder US findings were
      supraspinatus tendinitis in 54.4%, acromioclavicular joint degeneration in 26.5%,
      bicipital tendinitis in 20.6%, and subacromial-subdeltoid bursitis in 19.1%.
      There was a statistically significant difference between MRI and US findings. The
      results were not compatible with each other (P ? .05), and these findings were
      not consistent with each other since the kappa coefficient was under 0.40 for all
      these results. CONCLUSION: Although US is recommended as the first method in
      determining shoulder pathologies in hemiplegic patients, we suggest that MRI
      should be used as the first choice in hemiplegic patients with shoulder pain. MRI
      and US findings were not consistent, and US is dependent on the experience of the
      operator. MRI should be the first choice in cases where the diagnosis will affect
      the treatment choice due to the lack of correlation between US and MRI findings.

PMID- 24722038
TI  - Methylome diversification through changes in DNA methyltransferase sequence
      specificity.
AB  - Epigenetic modifications such as DNA methylation have large effects on gene
      expression and genome maintenance. Helicobacter pylori, a human gastric pathogen,
      has a large number of DNA methyltransferase genes, with different strains having
      unique repertoires. Previous genome comparisons suggested that these
      methyltransferases often change DNA sequence specificity through domain movement-
      the movement between and within genes of coding sequences of target recognition
      domains. Using single-molecule real-time sequencing technology, which detects N6
      methyladenines and N4-methylcytosines with single-base resolution, we studied
      methylated DNA sites throughout the H. pylori genome for several closely related
      strains. Overall, the methylome was highly variable among closely related
      strains. Hypermethylated regions were found, for example, in rpoB gene for RNA
      polymerase. We identified DNA sequence motifs for methylation and then assigned
      each of them to a specific homology group of the target recognition domains in
      the specificity-determining genes for Type I and other restriction-modification
      systems. These results supported proposed mechanisms for sequence-specificity
      changes in DNA methyltransferases. Knocking out one of the Type I specificity
      genes led to transcriptome changes, which suggested its role in gene expression.
      These results are consistent with the concept of evolution driven by DNA
      methylation, in which changes in the methylome lead to changes in the
      transcriptome and potentially to changes in phenotype, providing targets for
      natural or artificial selection.

PMID- 24722040
TI  - Extracorporeal shock wave therapy for the treatment of poststroke plantar-flexor
      muscles spasticity: a prospective open-label study.
AB  - OBJECTIVES: To assess the use of extracorporeal shock wave therapy (ESWT) for the
      treatment of equinus foot after stroke and to correlate the ESWT effect on
      spastic plantar-flexor muscles with echo intensity on the Heckmatt scale.
      METHODS: The prospective open-label study examined 23 patients with poststroke
      lower limb spasticity. Adults with spastic equinus foot after stroke received one
      ESWT session on hypertonic plantar-flexor muscles. The effect on spasticity,
      degree of passive ankle dorsiflexion, and neurophysiological values were
      evaluated. Before treatment, participants underwent a sonography evaluation of
      calf muscles to identify echo intensity on the Heckmatt scale. RESULTS:
      Immediately after the session, ESWT induced a statistically significant reduction
      in muscle tone, increasing passive ankle dorsiflexion motion. At 30 days of
      follow-up, the effect persisted only in patients with echo intensity of spastic
      plantar-flexor muscles graded I, II, or III on the Heckmatt scale without any
      action related to spinal excitability. Mild adverse events were reported after
      the treatment but were resolved in a few days. CONCLUSIONS: ESWT is safe and
      efficacious for the treatment of poststroke plantar-flexor muscles spasticity,
      reducing muscle tone and improving passive ankle dorsiflexion motion. The effect
      was long lasting in subjects with echo intensity of calf muscles graded I, II, or
      III but was brief for echo intensity graded IV on the Heckmatt scale. The ESWT
      effect did not appear to be related to spinal excitability.

PMID- 24722041
TI  - Individualized treadmill and strength training for chronic stroke rehabilitation:
      effects of imbalance.
AB  - BACKGROUND AND PURPOSE: Stroke survivors often have significant walking
      limitations and are at high risk for falling. Treadmill training, as a
      rehabilitation approach in stroke survivors, and its relationship to balance
      ability has not been widely studied. The main goal of this study was to
      investigate the effectiveness of an individualized treadmill-strength training
      protocol on functional outcomes in chronic stroke survivors. METHODS: Thirty
      adult participants with chronic stroke were recruited from 1 European and 4
      Middle Eastern countries. Each completed 36 sessions of treadmill-strength
      training. The rehabilitation protocol was individualized according to each
      patient's cardiovascular fitness. Ten-meter walk test (10MWT), Berg Balance Scale
      (BBS), and 6-minute walk test (6MWT) were measured before (T0) and after training
      (T1) and 6 months later (T2). Paired t tests were used to test differences with
      training (T1 - T0) and retention after training (T2 - T1). RESULTS: Increases in
      all 3 measures from T0 to T1 were significant. There were no changes in 10MWT and
      BBS from T1 to T2, but 6MWT tended to increase. Separate analyses for subjects
      with BBS scores <41 at T0 demonstrated comparatively greater improvements from T0
      to T1 than in those with BBS scores ?40. Those with low scores also significantly
      increased from T1 to T2 in both walk tests. DISCUSSION: These findings suggest
      that a protocol combining treadmill with strength training has beneficial long
      term effects on functional walking measures after chronic stroke, especially in
      patients who initially have low balance ability.

PMID- 24722042
TI  - Impact of BDNF -196 G>A and BDNF -270 C>T polymorphisms on stroke rehabilitation
      outcome: sex and age differences.
AB  - BACKGROUND: Genetic factors, including gene polymorphisms, are promising in
      determining stroke rehabilitation outcome. Brain-derived neurotrophic factor
      (BDNF) is one of the most attractive because of its role in neuroplasticity and
      brain repair. OBJECTIVE: The aim of present study was to assess the role of BDNF 
      196 G?A (val66met) and -270 C?T on clinical parameters and functional outcome in
      patients with ischemic and hemorrhagic stroke. Additional analyses according to
      sex and age (<=55 and ?55 years) were performed. METHODS: Three hundred thirty
      eight patients (287 with ischemic and 51 with hemorrhagic stroke) were evaluated
      in terms of neurological deficit (National Institute of Heath Stroke Scale
      [NIHSS]), activities of daily living (Barthel Index [BI]), and everyday
      functionality (Rankin score [RS]) before and after rehabilitation. BDNF
      polymorphism genotyping was performed by polymerase chain reaction restriction
      fragment length polymorphism analysis. RESULTS: In multivariative analysis,
      unfavorable outcome of stroke rehabilitation (RS >=2) was associated with
      independent factors: ischemic stroke (odds ratio [OR], 2.59; 95% CI, 1.03-6.47),
      female gender (OR, 2.80; 95% CI, 1.39-5.64), depression (OR, 4.24; 95% CI, 1.45
      12.35), falls (OR, 2.61; 95% CI, 1.16-5.87), and BDNF -196 GG polymorphism (OR,
      2.18; 95% CI, 1.09-4.35). The differences of functional parameters measured with
      BI and RS on admission and at discharge are apparent only for comparisons between
      patients <=55 and ?55 years old carrying BDNF -196 GA+AA genotypes but not in
      those carrying -196 GG genotype; the differences were evident in women but not in
      men. CONCLUSIONS: BDNF -196 G?A polymorphism might affect functional outcome of
      stroke rehabilitation, but this hypothesis needs further verification.

PMID- 24722043
TI  - Does participation in standardized aerobic fitness training during inpatient
      stroke rehabilitation promote engagement in aerobic exercise after discharge? A
      cohort study.
AB  - OBJECTIVE: To determine whether attending an aerobic fitness program during
      inpatient stroke rehabilitation is associated with increased participation in
      physical activity after discharge. DESIGN: This was a prospective cohort study.
      Patients who received inpatient stroke rehabilitation and were discharged into
      the community (n = 61; mean age, 65 years) were recruited. Thirty-five
      participants attended a standardized aerobic fitness program during inpatient
      rehabilitation, whereas 26 did not. The Physical Activity Scale for Individuals
      with Physical Disabilities (PASIPD) and adherence to the American College of
      Sports Medicine (ACSM) guidelines were assessed up to 6 months after discharge.
      RESULTS: Participants in the fitness group had PASIPD scores and adherence to
      ACSM guidelines similar to those of participants in the nonfitness group up to 6
      months after discharge. There was no significant correlation between volume of
      exercise performed during the inpatient program and amount of physical activity
      after discharge. CONCLUSION: Participation in an inpatient fitness program did
      not increase participation in physical activity after discharge in individuals
      with stroke. A new model of care that encourages patients to pursue physical
      activity after discharge and reduces the potential barriers to participation
      should be developed.

PMID- 24722044
TI  - Evaluating stroke patients' awareness of risk factors and readiness to change
      stroke risk-related behaviors in a randomized controlled trial.
AB  - PURPOSE: To identify the effects of a brief educational intervention on stroke
      patients' recall and recognition of risk factors and performance of and stage of
      change for stroke risk-related behaviors. METHODS: Sixty-six patients with stroke
      participated in a multisite randomized controlled trial. The intervention group
      (n = 35) received a brief education intervention (tailored written stroke
      information, verbal reinforcement of information for 3 months after discharge,
      and provision of a telephone number). The control group (n = 31) received usual
      care. Unprompted recall (personal and general), prompted recognition of risk
      factors (0-13), and performance of (0-10) and stage of change for up to 7 stroke
      risk-related behaviors were assessed before and 3 months after discharge.
      RESULTS: No significant between-group differences were found. For all
      participants over time, there were significant improvements for personal (mean
      difference [MD], 0.3; 95% CI, 0.004-0.69; P = .05) and general (MD, 0.6; 95% CI,
      0.09-1.16; P = .02) risk factor recall; performance of stroke risk-related
      behaviors (MD, 0.8; 95% CI, 0.28-1.26; P < .01); and progression from a nonaction
      to an action stage of change for 4 of 7 behaviors over time. There was a
      significant decline in total risk factor recognition scores (MD, -0.8; 95% CI,
      0.39-1.13; P < .01). CONCLUSION: Stroke patients' unprompted recall of risk
      factors and performance of risk-related behaviors improved over time; readiness
      to change risk-related behaviors progressed for some behaviors. A brief
      educational intervention did not improve risk factor awareness or behavior change
      more than usual care.

PMID- 24722045
TI  - Family Intervention: Telephone Tracking (FITT): a pilot stroke outcome study.
AB  - OBJECTIVE: The goal of this study was to preliminarily test the efficacy of a
      telephone intervention, Family Intervention: Telephone Tracking, designed to
      assist stroke survivors and their primary caregivers during the first 6 months
      after stroke. METHOD: Forty-nine stroke survivors and their caregivers were
      randomly assigned to treatment as usual or treatment as usual plus the telephone
      intervention. Global outcomes are reported for health care utilization, family
      functioning, and general functioning. RESULTS: Family and general functioning
      were positively and significantly changed at 3 and 6 months. Health care
      utilization was positively and significantly changed at 3 months. CONCLUSION:
      Findings suggest that the model has the potential to decrease health care
      utilization and improve quality of life for stroke survivors and their
      caregivers. Further study is warranted.

PMID- 24722046
TI  - Employment after stroke: report of a state of the science symposium.
AB  - For many stroke survivors, returning to work becomes an important emotional and
      functional milestone in signaling recovery. It can also provide needed financial
      support and reduce the burden placed on society in the form of government
      assistance. The complex nature of the return-to-work process involves many
      factors that may support or interfere with reintegration into the workforce. For
      the purpose of examining this important topic more closely, the Rehabilitation
      Research & Training Center on Enhancing the Functional and Employment Outcomes of
      Individuals Who Experience a Stroke held a State of the Science Symposium on
      employment after stroke on November 7, 2011, which was supported by the US
      Department of Education, National Institute on Disability and Rehabilitation
      Research. Six questions were posed to the symposium members, who developed
      research and policy recommendations to address the issues facing stroke survivors
      seeking to return to work. 

PMID- 24722047
TI  - Efficacy of therapeutic ultrasound and transcutaneous electrical nerve
      stimulation compared with botulinum toxin type A in the treatment of spastic
      equinus in adults with chronic stroke: a pilot randomized controlled trial.
AB  - BACKGROUND: Therapeutic ultrasound and transcutaneous electrical nerve
      stimulation (TENS) have been described as being effective in the treatment of
      spasticity. No previous study compared these physical modalities with a first
      line treatment for spasticity, such as botulinum toxin type A. OBJECTIVE: To
      compare the effects of therapeutic ultrasound and TENS with botulinum toxin type
      A on spasticity after stroke. METHODS: Thirty patients with chronic stroke and
      spastic equinus were randomly assigned to 3 groups: 1 group received therapeutic
      ultrasound to the affected leg calf muscles, 1 group underwent TENS to the tibial
      nerve of the affected leg, and 1 group was injected with onabotulinum toxin A in
      the spastic gastrocnemius. All patients were evaluated immediately before
      treatment and 15, 30, and 90 days after the first clinical evaluation. The
      following outcome measures were considered: ankle passive dorsiflexion range of
      motion and the modified Ashworth scale. RESULTS: Patients injected with botulinum
      toxin type A had significantly better ankle passive range of motion than those
      treated with physical modalities at all posttreatment evaluations. At second and
      third posttreatment evaluations, the modified Ashworth scale indicated
      significantly greater improvement in patients injected with botulinum toxin type
      A than in those treated with physical modalities. No difference was found between
      groups treated with physical modalities. CONCLUSIONS: Our findings support the
      hypothesis that botulinum toxin type A is more effective than therapeutic
      ultrasound and TENS for treating focal spasticity in patients with chronic
      stroke.

PMID- 24722048
TI  - Mutations in IDH1, IDH2, and in the TERT promoter define clinically distinct
      subgroups of adult malignant gliomas.
AB  - Frequent mutations in isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2) and the
      promoter of telomerase reverse transcriptase (TERT) represent two significant
      discoveries in glioma genomics. Understanding the degree to which these two
      mutations co-occur or occur exclusively of one another in glioma subtypes
      presents a unique opportunity to guide glioma classification and prognosis. We
      analyzed the relationship between overall survival (OS) and the presence of
      IDH1/2 and TERT promoter mutations in a panel of 473 adult gliomas. We
      hypothesized and show that genetic signatures capable of distinguishing among
      several types of gliomas could be established providing clinically relevant
      information that can serve as an adjunct to histopathological diagnosis. We found
      that mutations in the TERT promoter occurred in 74.2% of glioblastomas (GBM), but
      occurred in a minority of Grade II-III astrocytomas (18.2%). In contrast, IDH1/2
      mutations were observed in 78.4% of Grade II-III astrocytomas, but were uncommon
      in primary GBM. In oligodendrogliomas, TERT promoter and IDH1/2 mutations co
      occurred in 79% of cases. Patients whose Grade III-IV gliomas exhibit TERT
      promoter mutations alone predominately have primary GBMs associated with poor
      median OS (11.5 months). Patients whose Grade III-IV gliomas exhibit IDH1/2
      mutations alone predominately have astrocytic morphologies and exhibit a median
      OS of 57 months while patients whose tumors exhibit both TERT promoter and IDH1/2
      mutations predominately exhibit oligodendroglial morphologies and exhibit median
      OS of 125 months. Analyzing gliomas based on their genetic signatures allows for
      the stratification of these patients into distinct cohorts, with unique prognosis
      and survival. 

PMID- 24722049
TI  - Harmonic hopping, and both punctuated and gradual evolution of acoustic
      characters in Selasphorus hummingbird tail-feathers.
AB  - Models of character evolution often assume a single mode of evolutionary change,
      such as continuous, or discrete. Here I provide an example in which a character
      exhibits both types of change. Hummingbirds in the genus Selasphorus produce
      sound with fluttering tail-feathers during courtship. The ancestral character
      state within Selasphorus is production of sound with an inner tail-feather, R2,
      in which the sound usually evolves gradually. Calliope and Allen's Hummingbirds
      have evolved autapomorphic acoustic mechanisms that involve feather-feather
      interactions. I develop a source-filter model of these interactions. The 'source'
      comprises feather(s) that are both necessary and sufficient for sound production,
      and are aerodynamically coupled to neighboring feathers, which act as filters.
      Filters are unnecessary or insufficient for sound production, but may evolve to
      become sources. Allen's Hummingbird has evolved to produce sound with two
      sources, one with feather R3, another frequency-modulated sound with R4, and
      their interaction frequencies. Allen's R2 retains the ancestral character state,
      a ~1 kHz "ghost" fundamental frequency masked by R3, which is revealed when R3 is
      experimentally removed. In the ancestor to Allen's Hummingbird, the dominant
      frequency has 'hopped' to the second harmonic without passing through
      intermediate frequencies. This demonstrates that although the fundamental
      frequency of a communication sound may usually evolve gradually, occasional jumps
      from one character state to another can occur in a discrete fashion. Accordingly,
      mapping acoustic characters on a phylogeny may produce misleading results if the
      physical mechanism of production is not known. 

PMID- 24722050
TI  - Comparative analyses of lung transcriptomes in patients with alveolar capillary
      dysplasia with misalignment of pulmonary veins and in foxf1 heterozygous knockout
      mice.
AB  - Alveolar Capillary Dysplasia with Misalignment of Pulmonary Veins (ACDMPV) is a
      developmental disorder of the lungs, primarily affecting their vasculature. FOXF1
      haploinsufficiency due to heterozygous genomic deletions and point mutations have
      been reported in most patients with ACDMPV. The majority of mice with
      heterozygous loss-of-function of Foxf1 exhibit neonatal lethality with evidence
      of pulmonary hemorrhage in some of them. By comparing transcriptomes of human
      ACDMPV lungs with control lungs using expression arrays, we found that several
      genes and pathways involved in lung development, angiogenesis, and in pulmonary
      hypertension development, were deregulated. Similar transcriptional changes were
      found in lungs of the postnatal day 0.5 Foxf1+/- mice when compared to their
      wildtype littermate controls; 14 genes, COL15A1, COL18A1, COL6A2, ESM1, FSCN1,
      GRINA, IGFBP3, IL1B, MALL, NOS3, RASL11B, MATN2, PRKCDBP, and SIRPA, were found
      common to both ACDMPV and Foxf1 heterozygous lungs. Our results advance knowledge
      toward understanding of the molecular mechanism of ACDMPV, lung development, and
      its vasculature pathology. These data may also be useful for understanding
      etiologies of other lung disorders, e.g. pulmonary hypertension, bronchopulmonary
      dysplasia, or cancer. 

PMID- 24722052
TI  - Patterns and predictors of local health department accreditation in Missouri.
AB  - BACKGROUND: The Healthy People 2020 goal for the public health system is "to
      ensure that Federal, State, Tribal, and local health agencies have the necessary
      infrastructure to effectively provide essential public health services." To
      address this goal, Missouri established the first statewide, voluntary
      accreditation program of local health departments (LHDs) and began accrediting
      the LHDs in 2003. The purpose of this study was to identify organizational,
      structural, and workforce factors related to accreditation status of LHDs in
      Missouri. METHODS: Using data from the National Association of County & City
      Health Officials (2010) and the Missouri Department of Health & Senior Services
      (2012), binary logistic regression analysis was performed to predict
      accreditation status of LHDs. Likelihood ratio tests were used to examine whether
      the addition of each predictor added significantly to the model compared with a
      model including total revenues alone. Adjusted odds ratios (aORs), 95% confidence
      intervals, the significance level of the likelihood ratio test, and the overall
      Nagelkerke pseudo-R for each model are reported. RESULTS: Having a community
      health improvement plan (aOR = 6.2), a strategic plan (aOR = 7.9), evaluating
      programs (aOR = 3.6), being in a region with a high proportion of accredited LHDs
      (aOR = 5.5), and participating in multijurisdictional collaborations (aOR = 6.4)
      all increased the likelihood of accreditation. Barriers of time (aOR = 0.1) and
      cost (aOR = 0.3) were negatively associated with accreditation. CONCLUSIONS:
      Accredited LHDs were more likely to have completed the prerequisites for
      accreditation and collaborate with other LHDs. These activities help LHDs meet
      the accreditation standards. In addition, with shrinking budgets, LHDs will need
      additional financial and technical support to achieve accreditation. Assisting
      LHDs to find ways to increase the staff is important. Through collaborations with
      other LHDs, regional or multicounty positions can be created. Also collaborations
      with universities, specifically colleges or schools of public health, can provide
      opportunities for internships at LHDs giving practical experience while providing
      important assistance to LHDs.

PMID- 24722051
TI  - Protein accumulation in the endoplasmic reticulum as a non-equilibrium phase
      transition.
AB  - Several neurological disorders are associated with the aggregation of aberrant
      proteins, often localized in intracellular organelles such as the endoplasmic
      reticulum. Here we study protein aggregation kinetics by mean-field reactions and
      three dimensional Monte carlo simulations of diffusion-limited aggregation of
      linear polymers in a confined space, representing the endoplasmic reticulum. By
      tuning the rates of protein production and degradation, we show that the system
      undergoes a non-equilibrium phase transition from a physiological phase with
      little or no polymer accumulation to a pathological phase characterized by
      persistent polymerization. A combination of external factors accumulating during
      the lifetime of a patient can thus slightly modify the phase transition control
      parameters, tipping the balance from a long symptomless lag phase to an
      accelerated pathological development. The model can be successfully used to
      interpret experimental data on amyloid-beta clearance from the central nervous
      system. 

PMID- 24722053
TI  - Oxidative stress and DNA damage responses to phenanthrene exposure in the
      estuarine guppy Poecilia vivipara.
AB  - Despite ubiquitous phenanthrene contamination in aquatic coastal areas, little is
      known regarding its potential effects on estuarine fishes. The present work
      evaluated the response of a large suite of oxidative stress- and DNA damage
      related biomarkers to phenanthrene exposure (10, 20 and 200 MUg L(-1), 96 h)
      using DMSO as the solvent in estuarine guppy Poecilia vivipara (salinity 24 psu).
      Phenanthrene affected oxidative stress-related parameters, and decreased
      antioxidant defenses and reactive oxygen species in the gills and muscle overall.
      Lipid peroxidation occurred in muscle at 200 MUg L(-1) phenanthrene. Genotoxicity
      was increased at 20 MUg L(-1), while 200 MUg L(-1) caused a relative decrease in
      erythrocyte release into the bloodstream. These findings indicated that
      phenanthrene is genotoxic and can induce oxidative stress, depending on tissue
      and phenanthrene concentration analyzed. Thus, some of the biomarkers analyzed in
      the present study are sufficiently sensitive to monitor the exposure of the guppy
      P. vivipara to phenanthrene in salt water. However, further studies are required
      for a better interpretation of the dose-response patterns observed. 

PMID- 24722054
TI  - Cobblestone-area forming cells derived from patients with mantle cell lymphoma
      are enriched for CD133+ tumor-initiating cells.
AB  - Mantle cell lymphoma (MCL) is associated with a significant risk of therapeutic
      failure and disease relapse, but the biological origin of relapse is poorly
      understood. Here, we prospectively identify subpopulations of primary MCL cells
      with different biologic and immunophenotypic features. Using a simple culture
      system, we demonstrate that a subset of primary MCL cells co-cultured with either
      primary human mesenchymal stromal cells (hMSC) or murine MS-5 cells form in
      cobblestone-areas consisting of cells with a primitive immunophenotype (CD19
      CD133+) containing the chromosomal translocation t (11;14)(q13;q32)
      characteristic of MCL. Limiting dilution serial transplantation experiments
      utilizing immunodeficient mice revealed that primary MCL engraftment was only
      observed when either unsorted or CD19-CD133+ cells were utilized. No engraftment
      was seen using the CD19+CD133- subpopulation. Our results establish that primary
      CD19-CD133+ MCL cells are a functionally distinct subpopulation of primary MCL
      cells enriched for MCL-initiating activity in immunodeficient mice. This rare
      subpopulation of MCL-initiating cells may play an important role in the
      pathogenesis of MCL. 

PMID- 24722055
TI  - Extracellular alpha-synuclein leads to microtubule destabilization via GSK-3beta
      dependent Tau phosphorylation in PC12 cells.
AB  - alpha-Synuclein (ASN) plays an important role in pathogenesis of Parkinson's
      disease (PD) and other neurodegenerative disorders. Novel and most interesting
      data showed elevated tauopathy in PD and suggested relationship between ASN and
      Tau protein. However, the mechanism of ASN-evoked Tau protein modification is not
      fully elucidated. In this study we investigated the role of extracellular ASN in
      Tau hyperphosphorylation in rat pheochromocytoma (PC12) cells and the involvement
      of glycogen synthase kinase-3beta (GSK-3beta) and cyclin-dependent kinase 5
      (CDK5) in ASN-dependent Tau modification. Our results indicated that exogenously
      added ASN increases Tau phosphorylation at Ser396. Accordingly, the GSK-3beta
      inhibitor (SB-216763) prevented ASN-evoked Tau hyperphosphorylation, but the CDK5
      inhibitor had no effect. Moreover, western blot analysis showed that ASN affected
      GSK-3beta via increasing of protein level and activation of this enzyme. GSK
      3beta activity evaluated by its phosphorylation status assay showed that ASN
      significantly increased the phosphorylation of this enzyme at Tyr216 with
      parallel decrease in phosphorylation at Ser9, indicative of stimulation of GSK
      3beta activity. Moreover, the effect of ASN on microtubule (MT) destabilization
      and cell death with simultaneous the involvement of GSK-3beta in these processes
      were analyzed. ASN treatment increased the amount of free tubulin and
      concomitantly reduced the amount of polymerized tubulin and SB-216763 suppressed
      these ASN-induced changes in tubulin, indicating that GSK-3beta is involved in
      ASN-evoked MT destabilization. ASN-induced apoptotic processes lead to decrease
      in PC12 cells viability and SB-216763 protected those cells against ASN-evoked
      cytotoxicity. Concluding, extracellular ASN is involved in GSK-3beta-dependent
      Tau hyperphosphorylation, which leads to microtubule destabilization. GSK-3beta
      inhibition may be an effective strategy for protecting against ASN-induced
      cytotoxicity. 

PMID- 24722056
TI  - Induction of adipocyte differentiation by polybrominated diphenyl ethers (PBDEs)
      in 3T3-L1 cells.
AB  - Polybrominated diphenyl ethers (PBDEs) are a class of brominated flame retardants
      that were extensively used in commercial products. PBDEs are ubiquitous
      environmental contaminants that are both lipophilic and bioaccumulative. Effects
      of PBDEs on adipogenesis were studied in the 3T3-L1 preadipocyte cell model in
      the presence and absence of a known adipogenic agent, dexamethasone (DEX). A PBDE
      mixture designed to mimic body burden of North Americans was tested, in addition
      to the technical mixture DE-71 and the individual congener BDE-47. The mixture,
      DE-71, and BDE-47 all induced adipocyte differentiation as assessed by markers
      for terminal differentiation [fatty acid binding protein 4 (aP2) and perilipin]
      and lipid accumulation. Characterization of the differentiation process in
      response to PBDEs indicated that adipogenesis induced by a minimally effective
      dose of DEX was enhanced by these PBDEs. Moreover, C/EBPalpha, PPARgamma, and
      LXRalpha were induced late in the differentiation process. Taken together, these
      data indicate that adipocyte differentiation is induced by PBDEs; they act in the
      absence of glucocorticoid and enhance glucocorticoid-mediated adipogenesis.

PMID- 24722057
TI  - Functional haemodynamic monitoring.
AB  - PURPOSE OF REVIEW: Functional haemodynamic monitoring is the assessment of the
      dynamic interactions of haemodynamic variables in response to a defined
      perturbation. RECENT FINDINGS: Fluid responsiveness can be predicted during
      positive pressure breathing by variations in venous return or left ventricular
      output using numerous surrogate markers, such as arterial pulse pressure
      variation (PPV), left ventricular stroke volume variation (SVV), aortic velocity
      variation, inferior and superior vena cavae diameter changes and pulse oximeter
      pleth signal variability. Similarly, dynamic changes in cardiac output to a
      passive leg raising manoeuvre can be used in any patient and measured invasively
      or noninvasively. However, volume responsiveness, though important, reflects only
      part of the overall spectrum of functional physiological variables that can be
      measured to define physiologic state and monitor response to therapy. The ratio
      of PPV to SVV defines central arterial elastance and can be used to identify
      those hypotensive patients who will not increase their blood pressure in response
      to a fluid challenge despite increasing cardiac output. Dynamic tissue O2
      saturation (StO2) responses to complete stop flow conditions, as can be created
      by measuring hand StO2 and occluding flow with a blood pressure cuff, assesses
      cardiovascular sufficiency and micro-circulatory blood flow distribution. They
      can be used to identify those ventilator-dependent individuals who will fail a
      spontaneous breathing trial or trauma patients in need of life-saving
      interventions. SUMMARY: Functional haemodynamic monitoring approaches are
      increasing in numbers, conditions in which they are useful and resuscitation
      protocol applications. This is a rapidly evolving field whose pluripotential is
      just now being realized.

PMID- 24722058
TI  - Ultrasonic evaluation of the heart.
AB  - PURPOSE OF REVIEW: To discuss the role of echocardiography for the hemodynamic
      evaluation of critically ill patients. RECENT FINDINGS: In addition to its
      crucial role in evaluating heart abnormalities as in the classical cardiological
      approach, echocardiography is now frequently used by intensivists for noninvasive
      hemodynamic evaluation of the critically ill patient. Using echocardiography, it
      is possible to measure cardiac output, intravascular pressures and volumes,
      systolic and diastolic function of both ventricles, and preload responsiveness.
      This not only allows characterization of the precise nature of hemodynamic
      alterations in patients with circulatory and respiratory failure, but also
      provides guidance for hemodynamic optimization and optimization of ventilatory
      settings. There are now many data showing how echocardiography can be useful in
      detecting otherwise unrecognized myocardial depression in sepsis and right
      ventricular dysfunction in mechanically ventilated patients. The main limitation
      of echocardiography for hemodynamic monitoring is its intermittent nature. Hence,
      echocardiography is often combined with other monitoring devices, allowing
      continuous measurement of flow and triggering new echocardiographic evaluations.
      SUMMARY: Echocardiography has now become an important tool for hemodynamic
      evaluation of the critically ill patient. Echocardiography should be performed in
      most patients with circulatory and respiratory failure.

PMID- 24722059
TI  - Assessing effort and work of breathing.
AB  - PURPOSE OF REVIEW: Spontaneous breathing has been shown to induce both positive
      and negative effects on the function and on injury of lungs and diaphragm during
      critical illness; thus, monitoring of the breathing effort generated by the
      patient might be valuable for a better understanding of the mechanisms of disease
      and to set properly ventilation. The purpose of this review is to summarize the
      recent findings on the different techniques available to measure the patient's
      breathing effort, mainly during spontaneous assisted ventilation. RECENT
      FINDINGS: Although esophageal pressure measurement remains the solid reference
      technique to quantitate the breathing effort, other tools have been developed and
      tested. These include the diaphragmatic electromyogram, whose voltage is linearly
      related to the pressure generated by the diaphragm, ultrasound, which relies on
      the measurement of diaphragmatic displacement or thickening, and other
      approaches, which derive breathing effort solely from the airway flow and
      pressure tracings. SUMMARY: The development of measurement techniques and their
      introduction in clinical practice will allow us to understand the role of
      spontaneous breathing effort in the pathophysiology of lung injury and weaning
      failure, and how to adjust the breathing workload in an individual patient.

PMID- 24722061
TI  - Primary intestinal-type glandular lesions of the vagina: clinical, pathologic,
      and immunohistochemical features of 14 cases ranging from benign polyp to adenoma
      to adenocarcinoma.
AB  - Primary intestinal-type glandular lesions of the vagina are rare. We report a
      series of 14 lesions, including 1 intestinal-type polyp without neoplastic
      features, 3 adenomas (2 with high-grade dysplasia), and 10 adenocarcinomas.
      Patients ranged in age from 20 to 86 years (mean 60 y) and presented with vaginal
      bleeding or a mass. No history of diethylstilbestrol exposure, adenosis, or
      endometriosis was elicited in any patient. The lesions were mostly polypoid,
      small (0.8 to 2.0 cm), and located in the posterior (6 cases) and lower (7 cases)
      vagina. One carcinoma metastasized to a para-aortic lymph node; the others were
      confined to the vagina. The neoplasms exhibited histologic features identical to
      those seen in primary large intestinal tumors, including variable numbers of
      goblet cells and in 1 case neuroendocrine cells. Five of the adenocarcinomas
      contained areas consistent with a precursor adenoma. In 3 cases, a benign
      urothelium-lined duct was adjacent to the lesion, and in 2 patients benign
      intestinal-type epithelium was present; no other potential benign precursor
      lesions were seen. Immunohistochemical analysis was performed on 6 cases; the
      tumors were positive for CDX-2 (6/6), CK20 (5/6), CEA (5/5), CK7 (4/6), and CA
      125 (2/4) and were negative for ER (0/6) and p16 (0/2). Clinical outcome data
      were available in 3 patients with adenocarcinomas; 1 died of disease in <1 year,
      and 2 were alive with no evidence of disease at 2 and 7 years. The pertinent
      literature is reviewed, and the potential origin and differential diagnosis of
      these lesions are discussed. 

PMID- 24722060
TI  - Quantitative detection of epstein-barr virus DNA in cerebrospinal fluid and blood
      samples of patients with relapsing-remitting multiple sclerosis.
AB  - The presence of Epstein-Barr Virus (EBV) DNA in cerebrospinal fluid (CSF) and
      peripheral blood (PB) samples collected from 55 patients with clinical and
      radiologically-active relapsing-remitting MS (RRMS) and 51 subjects with other
      neurological diseases was determined using standardized commercially available
      kits for viral nucleic acid extraction and quantitative EBV DNA detection. Both
      cell-free and cell-associated CSF and PB fractions were analyzed, to distinguish
      latent from lytic EBV infection. EBV DNA was detected in 5.5% and 18.2% of cell
      free and cell-associated CSF fractions of patients with RRMS as compared to 7.8%
      and 7.8% of controls; plasma and peripheral blood mononuclear cells (PBMC)
      positivity rates were 7.3% and 47.3% versus 5.8% and 31.4%, respectively. No
      significant difference in median EBV viral loads of positive samples was found
      between RRMS and control patients in all tested samples. Absence of statistically
      significant differences in EBV positivity rates between RRMS and control
      patients, despite the use of highly sensitive standardized methods, points to the
      lack of association between EBV and MS disease activity. 

PMID- 24722063
TI  - Clinical, morphologic, phenotypic, and genetic evidence of cyclin D1-positive
      diffuse large B-cell lymphomas with CYCLIN D1 gene rearrangements.
AB  - Overexpression of cyclin D1 in diffuse large B-cell lymphomas (DLBCLs) is
      observable in about 5% of cases and is linked to gains of additional CYCLIN D1
      gene copies or deregulation at the mRNA level. All cyclin D1-positive DLBCL cases
      reported so far lack the canonical t(11;14)(q13;q32) translocation that is a
      genetic hallmark and the primary cause of cyclin D1 overexpression in mantle cell
      lymphoma (MCL). Using standard histologic and genetic techniques, complemented
      with genome-wide aberration analysis by array comparative genomic hybridization,
      we characterized 2 exceptional cases of blastoid B-cell lymphomas with cyclin D1
      overexpression, both bearing genetic rearrangements in the CYCLIN D1 gene locus.
      One of them had a t(11;14)(q13;q32) translocation and featured morphology,
      immunophenotype, and genetic copy number aberrations typical of DLBCL. The second
      case had a complex t(4;11;14) translocation, but the other features were
      intermediate between DLBCL and MCL and did not allow unambiguous classification
      in any of the current diagnostic lymphoma categories. On the basis of these
      findings, we conclude that detection of t(11;14) should not preclude a diagnosis
      of cyclin D1-positive DLBCL when all other parameters are in agreement with such
      a diagnosis. Moreover, a yet unacknowledged diagnostic "gray zone" may exist
      between DLBCL and MCL. 

PMID- 24722064
TI  - Structural dynamics of GaN microcrystals in Evolutionary Selection Selective Area
      Growth probed by X-ray microdiffraction.
AB  - A method to grow high quality, single crystalline semiconductor material
      irrespective of the substrate would allow a cost-effective improvement to
      functionality and performance of optoelectronic devices. Recently, a novel type
      of substrate-insensitive growth process called Evolutionary Selection Selective
      Area Growth (ES-SAG) has been proposed. Here we report the use of X-ray
      microdiffraction to study the structural properties of GaN microcrystals grown by
      ES-SAG. Utilizing high resolution in both direct and reciprocal spaces, we have
      unraveled structural dynamics of GaN microcrystals in growth structures of
      different dimensions. It has been found that the geometric proportions of the
      growth constrictions play an important role: 2.6 MUm and 4.5 MUm wide growth
      tunnels favor the evolutionary selection mechanism, contrary to the case of 8.6
      MUm growth tunnels. It was also found that GaN microcrystal ensembles are
      dominated by slight tensile strain irrespective of growth tunnel shape.

PMID- 24722065
TI  - Piezoelectric monolayers as nonlinear energy harvesters.
AB  - We study the dynamics of h-BN monolayers by first performing ab-initio
      calculations of the deformation potential energy and then solving numerically a
      Langevine-type equation to explore their use in nonlinear vibration energy
      harvesting devices. An applied compressive strain is used to drive the system
      into a nonlinear bistable regime, where quasi-harmonic vibrations are combined
      with low-frequency swings between the minima of a double-well potential. Due to
      its intrinsic piezoelectric response, the nonlinear mechanical harvester
      naturally provides an electrical power that is readily available or can be stored
      by simply contacting the monolayer at its ends. Engineering the induced
      nonlinearity, a 20 nm2 device is predicted to harvest an electrical power of up
      to 0.18 pW for a noisy vibration of 5 pN.

PMID- 24722062
TI  - HOXB13 G84E-related familial prostate cancers: a clinical, histologic, and
      molecular survey.
AB  - Recent genetic epidemiologic studies identified a germline mutation in the
      homeobox transcription factor, HOXB13 G84E, which is associated with markedly
      increased risk for prostate cancer, particularly early-onset hereditary prostate
      cancer. The histomorphologic and molecular features of cancers arising in such
      carriers have not been studied. Here, we reviewed prostatectomy specimens from 23
      HOXB13 G84E mutation carriers, mapping the total cancer burden by anatomically
      distinct cancer focus and evaluating morphologic features. We also assessed basic
      molecular subtypes for all cancer foci (ERG/SPINK1 status) by dual
      immunohistochemistry staining on full sections. The cohort showed a median age of
      58 years, a median serum PSA level of 5.7 ng/mL, and a median of 6 cancer foci
      (range, 1 to 14) per case. Of evaluable cases, dominant foci were Gleason score 6
      in 23%, 3+4=7 in 41%, 4+3=7 in 23%, and >=8 in 14%; biochemical recurrence was
      observed in 1 case over a median of 36 months follow-up. Histologic review found
      a high prevalence of cases showing cancers with a spectrum of features previously
      described with pseudohyperplastic carcinomas, with 45% of cases showing a
      dominant focus with such features. Molecular subtyping revealed a strikingly low
      prevalence of ERG cancer with increased prevalence of SPINK1 cancer (dominant
      focus ERG 17%, SPINK1 26%, ERG/SPINK1 52%, single ERG/SPINK1 focus 4%). One
      ERG/SPINK1 dominant focus showed aberrant p63 immunophenotype. In summary, HOXB13
      G84E variant-related prostate cancers show frequent pseudohyperplastic-type
      features and markedly low prevalence of ERG cancers relative to unselected cases
      and, especially, to early-onset cohorts. These findings suggest that novel
      molecular pathways may drive disease in HOXB13 G84E carriers. 

PMID- 24722066
TI  - A homozygous mutation, c.736T>A (p.C246S), in LIPH gene in a patient manifesting
      woolly hair, hypotrichosis, hearing difficulty, cleft palate and amblyopia.

PMID- 24722068
TI  - A quick guide to genomics and bioinformatics training for clinical and public
      audiences.

PMID- 24722069
TI  - Presidential address.

PMID- 24722067
TI  - Androgen receptor splice variants activating the full-length receptor in
      mediating resistance to androgen-directed therapy.
AB  - Upregulation of constitutively-active androgen receptor splice variants (AR-Vs)
      has been implicated in AR-driven tumor progression in castration-resistant
      prostate cancer. To date, functional studies of AR-Vs have been focused mainly on
      their ability to regulate gene expression independent of the full-length AR (AR
      FL). Here, we showed that AR-V7 and ARv567es, two major AR-Vs, both facilitated
      AR-FL nuclear localization in the absence of androgen and mitigated the ability
      of the antiandrogen enzalutamide to inhibit AR-FL nuclear trafficking. AR-V bound
      to the promoter of its specific target without AR-FL, but co-occupied the
      promoter of canonical AR target with AR-FL in a mutually-dependent manner. AR-V
      expression attenuated both androgen and enzalutamide modulation of AR-FL
      activity/cell growth, and mitigated the in vivo antitumor efficacy of
      enzalutamide. Furthermore, ARv567es levels were upregulated in xenograft tumors
      that had acquired enzalutamide resistance. Collectively, this study highlights a
      dual function of AR-Vs in mediating castration resistance. In addition to trans
      activating target genes independent of AR-FL, AR-Vs can serve as a "rheostat" to
      control the degree of response of AR-FL to androgen-directed therapy via
      activating AR-FL in an androgen-independent manner. The findings shed new
      insights into the mechanisms of AR-V-mediated castration resistance and have
      significant therapeutic implications. 

PMID- 24722070
TI  - Valedictory address.

PMID- 24722071
TI  - Dentist suicides: speculation and myths.

PMID- 24722072
TI  - Natural disasters: offering help.

PMID- 24722073
TI  - Ethical dilemmas: guidelines without context.

PMID- 24722074
TI  - The trouble with guidelines.

PMID- 24722075
TI  - Investigation: sugar: what can we learn from the anti-smoking campaign?

PMID- 24722076
TI  - A dentist's life: the dentist in the aerial hoop.

PMID- 24722079
TI  - Conference reviews: the Ninth Annual Young Dentist Conference.

PMID- 24722090
TI  - Debate: short-term orthodontics.
AB  - Debate based on an opinion article published in the British Dental Journal
      entitled 'Truth or consequences: the potential implications of short-term
      cosmetic orthodontics for general dental practitioners' by R. A. C. Chate ( 2013;
      215: 551-553; www.nature.com/bdj/journal/v215/n11/full/sj.bdj.2013.1140.html). 

PMID- 24722091
TI  - Dentists in the US should be integrated into the hospital team.
AB  - Few dentists play integrated roles within hospital settings and few hospital
      emergency rooms have dentists. Existing research shows that only 67% of ER visits
      for dental problems are managed appropriately. Every year Americans die in
      hospital after being admitted because of dental disease and a recent study found
      that 20 people died after such hospitalisations in the United States in 2008.
      Authors of the current correspondence have conducted extensive research on
      characteristics of emergency room visits and hospitalisations due to various
      dental conditions using a nationwide dataset for the United States. This opinion
      article is intended to provoke discussion about the restructuring of hospitals to
      integrate oral health professionals into the hospital team. 

PMID- 24722092
TI  - Minimal intervention dentistry II: part 4. Minimal intervention techniques of
      preparation and adhesive restorations. The contribution of the sono-abrasive
      techniques.
AB  - The concept of minimal intervention in oral medicine is based on advances in
      biological sciences applied to the dental organ. Many cultural barriers, economic
      as well as technical, have thwarted the application of micro-invasive
      conservative techniques by the general practitioner. Emerging technologies do not
      remove all obstacles but promote the integration of less invasive techniques in
      daily practice. Sono-abrasion is a technique for the selective preparation of
      enamel and dentine offering excellent efficacy, quality and safety. The authors
      describe the therapeutic principles, the choice of instrumentation and its mode
      of action and discuss its interest in adhesive restorative dentistry. The
      illustrated clinical situations focus on the preservation and optimisation of
      tissue bonding for both initial lesions and advanced lesions. 

PMID- 24722093
TI  - Specialist management of routine dental procedures in adults with refractory
      epilepsy.
AB  - Little published information exists about the management of dental treatment
      procedures for people with epilepsy who, despite their medication, continue to
      have seizures. This paper draws on relevant literature in neurology and
      anaesthetics to provide a multi-speciality consensus on methods of assessment and
      adjunctive treatment options in order to manage the risk of a clinically
      significant seizure occurring during a procedure. It aims to enhance current
      guidelines and practice in the provision of specialist care for this diverse
      group. 

PMID- 24722094
TI  - Evidence not practised: the underutilisation of preventive fissure sealants.
AB  - International and UK professional organisations, Cochrane systematic reviews, and
      international and UK guidance documents all support the application of preventive
      fissure sealants (PFSs) as an effective treatment for reducing caries. However,
      PFSs are well known to be underutilised in primary care. This paper collates data
      from PFS-relevant studies in Scotland, which has a large population of children
      at caries risk, to identify the beliefs and factors dentists perceive as
      influencing their decision not to provide this treatment. This information
      provides a platform to suggest how to increase the application of PFSs in this
      region (a standardised audit incorporating evidence-based behaviour change
      techniques, supplemental guidance on how to implement gold-standard
      recommendations in practice, training). This may also be relevant outside of
      Scotland, as well as to the implementation of other evidence-based behaviours in
      practice. 

PMID- 24722099
TI  - Summary of: type 2 diabetes risk screening in dental practice settings: a pilot
      study.
AB  - BACKGROUND: Dental surgeries are highlighted in the 2012 NICE guidance Preventing
      type 2 diabetes: risk identification and interventions for individuals at high
      risk as a suitable setting in which to encourage people to have a type 2 diabetes
      risk assessment. AIM: To assess the feasibility of implementing a type 2 diabetes
      risk screening pathway in dental settings using the NICE guidance tool. METHOD:
      The study was carried out over two weeks in June 2013. The validated tool in the
      NICE guidance was used to determine risk. This included a questionnaire and BMI
      measurement used to determine a risk score. Patients were rated low, increased,
      moderate or high risk. All patients were given written advice on healthy
      lifestyle. Patients who were moderate or high risk were referred to their general
      medical practitioners for further investigation. Participating dental teams were
      asked to nominate a member who would be responsible for overseeing the screening
      and training the other team members. RESULTS: A total of 166 patients took part
      in the pilot (58% male, 75% aged 49 years or younger and 77% were from BME
      groups). Twenty-six low risk patients (15.7%), 61 increased risk patients
      (36.7%), 49 moderate-risk patients (29.5%) and 30 high-risk patients (18.1%) were
      identified during the pilot. Fifteen of the 49 patients (30.6%) identified as
      moderate-risk and 6 of the 30 high-risk patients (20%) had visited their GP to
      discuss their type 2 diabetes risk in response to the screening. CONCLUSION: The
      pilot suggests that people at risk of developing type 2 diabetes could be
      identified in primary, community and secondary dental care settings. The main
      challenges facing dental staff were time constraints, limited manpower and the
      low number of patients who visited their GP for further advice.

PMID- 24722100
TI  - Summary of: International benchmarking of hospitalisations for impacted teeth: a
      10-year retrospective study from the United Kingdom, France and Australia.
AB  - BACKGROUND: The United Kingdom and its national healthcare system represent a
      unique comparison for many other developed countries (such as Australia and
      France), as the practice of prophylactic removal of third molars in the United
      Kingdom has been discouraged for nearly two decades, with clear guidelines issued
      by the National Institute of Health and Care Excellence (NICE) in 2000 to limit
      third molar removal to only pathological situations. No such guidelines exist in
      Australia or France. The healthcare systems in England, France and Australia all
      use the International Classification of Disease (ICD) coding system for
      diagnostic categorising of all admissions to hospitals. AIM: This study rested
      upon the opportunity of a universal coding system and semi-open access data to
      complete the first comparative study on an international scale of
      hospitalisations for removal of impacted teeth (between 99/00 and 08/09).
      RESULTS: Our international comparison revealed significant differences in rates
      of admission, with England having rates approximately five times less than
      France, and seven times less than Australia. Those results could be explained by
      the implementation of guidelines in the United Kingdom, and the absence of
      similar guidelines in France and Australia.

PMID- 24722101
TI  - An audit of cavity and crown preparations and two direct restorations carried out
      by foundation dentists in the Oxford and Wessex Deaneries.
AB  - It is likely that many foundation dentists (FDs) will have completed only minimal
      amounts of restorative dentistry for a number of months immediately prior to
      commencing work as FDs. Thus this audit aimed to assess the performance of the
      FDs when they carried out a number of simulated clinical exercises: amalgam
      cavities and restoration; Class IV resin composite restorations; and full crown
      preparations for metal-ceramic restorations. A total of 67 FDs completed the
      assessments and some results did indicate a high level of concern and need for
      further evaluation of restorative practice. 

PMID- 24722117
TI  - Donald Winstock.

PMID- 24722118
TI  - Patrick Sweeney.

PMID- 24722119
TI  - Type 2 diabetes risk screening in dental practice settings: a pilot study.
AB  - BACKGROUND: Dental surgeries are highlighted in the 2012 NICE guidance Preventing
      type 2 diabetes: risk identification and interventions for individuals at high
      risk as a suitable setting in which to encourage people to have a type 2 diabetes
      risk assessment. AIM: To assess the feasibility of implementing a type 2 diabetes
      risk screening pathway in dental settings using the NICE guidance tool. METHOD:
      The study was carried out over two weeks in June 2013. The validated tool in the
      NICE guidance was used to determine risk. This included a questionnaire and BMI
      measurement used to determine a risk score. Patients were rated low, increased,
      moderate or high risk. All patients were given written advice on healthy
      lifestyle. Patients who were moderate or high risk were referred to their general
      medical practitioners for further investigation. Participating dental teams were
      asked to nominate a member who would be responsible for overseeing the screening
      and training the other team members. RESULTS: A total of 166 patients took part
      in the pilot (58% male, 75% aged 49 years or younger and 77% were from BME
      groups). Twenty-six low risk patients (15.7%), 61 increased risk patients
      (36.7%), 49 moderate-risk patients (29.5%) and 30 high-risk patients (18.1%) were
      identified during the pilot. Fifteen of the 49 patients (30.6%) identified as
      moderate-risk and 6 of the 30 high-risk patients (20%) had visited their GP to
      discuss their type 2 diabetes risk in response to the screening. CONCLUSION: The
      pilot suggests that people at risk of developing type 2 diabetes could be
      identified in primary, community and secondary dental care settings. The main
      challenges facing dental staff were time constraints, limited manpower and the
      low number of patients who visited their GP for further advice.

PMID- 24722120
TI  - International benchmarking of hospitalisations for impacted teeth: a 10-year
      retrospective study from the United Kingdom, France and Australia.
AB  - BACKGROUND: The United Kingdom and its national healthcare system represent a
      unique comparison for many other developed countries (such as Australia and
      France), as the practice of prophylactic removal of third molars in the United
      Kingdom has been discouraged for nearly two decades, with clear guidelines issued
      by the National Institute of Health and Care Excellence (NICE) in 2000 to limit
      third molar removal to only pathological situations. No such guidelines exist in
      Australia or France. The healthcare systems in England, France and Australia all
      use the International Classification of Disease (ICD) coding system for
      diagnostic categorising of all admissions to hospitals. AIM: This study rested
      upon the opportunity of a universal coding system and semi-open access data to
      complete the first comparative study on an international scale of
      hospitalisations for removal of impacted teeth (between 99/00 and 08/09).
      RESULTS: Our international comparison revealed significant differences in rates
      of admission, with England having rates approximately five times less than
      France, and seven times less than Australia. Those results could be explained by
      the implementation of guidelines in the United Kingdom, and the absence of
      similar guidelines in France and Australia.

PMID- 24722121
TI  - RNA editome in rhesus macaque shaped by purifying selection.
AB  - Understanding of the RNA editing process has been broadened considerably by the
      next generation sequencing technology; however, several issues regarding this
      regulatory step remain unresolved--the strategies to accurately delineate the
      editome, the mechanism by which its profile is maintained, and its evolutionary
      and functional relevance. Here we report an accurate and quantitative profile of
      the RNA editome for rhesus macaque, a close relative of human. By combining
      genome and transcriptome sequencing of multiple tissues from the same animal, we
      identified 31,250 editing sites, of which 99.8% are A-to-G transitions. We
      verified 96.6% of editing sites in coding regions and 97.5% of randomly selected
      sites in non-coding regions, as well as the corresponding levels of editing by
      multiple independent means, demonstrating the feasibility of our experimental
      paradigm. Several lines of evidence supported the notion that the adenosine
      deamination is associated with the macaque editome--A-to-G editing sites were
      flanked by sequences with the attributes of ADAR substrates, and both the
      sequence context and the expression profile of ADARs are relevant factors in
      determining the quantitative variance of RNA editing across different sites and
      tissue types. In support of the functional relevance of some of these editing
      sites, substitution valley of decreased divergence was detected around the
      editing site, suggesting the evolutionary constraint in maintaining some of these
      editing substrates with their double-stranded structure. These findings thus
      complement the "continuous probing" model that postulates tinkering-based
      origination of a small proportion of functional editing sites. In conclusion, the
      macaque editome reported here highlights RNA editing as a widespread functional
      regulation in primate evolution, and provides an informative framework for
      further understanding RNA editing in human.

PMID- 24722123
TI  - Hoarseness after thyroidectomy: blame the endocrine surgeon alone?
AB  - OBJECTIVE: Hoarseness is a postoperative complication of thyroidectomy, mostly
      due to damage to the recurrent laryngeal nerve (RLN). Hoarseness may also be
      brought about via vocal cord dysfunction (VCD) due to injury of the vocal cords
      from manipulations during anesthesia, as well as from psychogenic disorders and
      respiratory and upper-GI related infections. We reviewed the literature aiming to
      explore these potential surgical and non-surgical causes of hoarseness beyond
      thyroidectomy and the role of the endocrine surgeon. Is he/she alone to blame?
      METHODS/MATERIAL: The MEDLINE/PubMed database was searched for publications with
      the medical subject heading "hoarseness" and keywords "thyroidectomy", "RLN",
      "VCD" or "intubation". We restricted our search till up to May 2013. RESULTS: In
      our final review we included 80 articles and abstracts that were accessible and
      available in English. We demonstrated the incidence of hoarseness stemming from
      surgical and non-surgical causes and also highlighted the role of intubation as a
      potential cause of injury-related VCD. CONCLUSIONS: Hoarseness is a relatively
      common complication of thyroidectomy, which can be attributed to many factors
      including surgeon's error or injuries during intubation as well as to other non
      surgical causes. However, compared to procedures such as cervical spine surgery,
      mediastinal surgery, esophagectomy and endarterectomy, thyroidectomy would seem
      to be a procedure with a relatively low rate of recurrent laryngeal nerve palsies
      (RLNPs). It is often difficult to determine whether the degree of hoarseness
      after thyroidectomy should be attributed only the surgical procedure itself or to
      other causes, for example intubation and extubation maneuvers. The differential
      diagnosis of postoperative hoarseness requires the use of specific tools, such as
      stroboscopy and intra- and extralaryngeal electromyography, while methods like
      acoustic voice analysis, with estimation of maximum phonation time and phonation
      frequency range, can distinguish between objective and subjective deterioration
      in the voice. The importance of medical history should be also emphasized.

PMID- 24722122
TI  - Obesity survival paradox in pneumonia: a meta-analysis.
AB  - BACKGROUND: It is unclear whether an 'obesity survival paradox' exists for
      pneumonia. Therefore, we conducted a meta-analysis to assess the associations
      between increased body mass index (BMI), pneumonia risk, and mortality risk.
      METHODS: Cohort studies were identified from the PubMed and Embase databases.
      Summary relative risks (RRs) with their corresponding 95% confidence intervals
      (CIs) were calculated using a random effects model. RESULTS: Thirteen cohort
      studies on pneumonia risk (n = 1,536,623), and ten cohort studies on mortality (n
      = 1,375,482) were included. Overweight and obese individuals were significantly
      associated with an increased risk of pneumonia (RR = 1.33, 95% CI 1.04 to 1.71, P
      = 0.02, I(2) = 87%). In the dose-response analysis, the estimated summary RR of
      pneumonia per 5 kg/m(2) increase in BMI was 1.04 (95% CI 1.01 to 1.07, P = 0.01,
      I(2) = 84%). Inversely, overweight and obese subjects were significantly
      associated with reduced risk of pneumonia mortality (RR = 0.83, 95% CI 0.77 to
      0.91, P < 0.01, I(2) = 34%). The estimated summary RR of mortality per 5 kg/m(2)
      increase in BMI was 0.95 (95% CI 0.93 to 0.98, P < 0.01, I(2) = 77%).
      CONCLUSIONS: This meta-analysis suggests that an 'obesity survival paradox'
      exists for pneumonia. Because this meta-analysis is based on observational
      studies, more studies are required to confirm the results.

PMID- 24722124
TI  - Thyroid involvement in hepatitis C - associated mixed cryoglobulinemia.
AB  - OBJECTIVE: The prevalence and clinical features of thyroid involvement in
      patients with hepatitis C virus-associated mixed cryoglobulinemia (MC+HCV) have
      been reviewed. DESIGN: A PubMed Medline search was conducted through December
      2011 to identify all studies that reported thyroid involvement in MC+HCV
      patients. Reference lists of the papers initially detected were manually searched
      to identify additional relevant reports. Studies had to contain sufficient and
      clear information to be included. RESULTS: In MC+HCV patients, the following
      thyroid autoimmune abnormalities were significantly more frequent than in
      controls: high levels of serum anti-thyroperoxidase autoantibody (AbTPO); high
      levels of serum AbTPO and/or anti-thyroglobulin autoantibody; humoral and
      ultrasonographical signs of thyroid autoimmunity (35% vs 16%); prevalence of
      subclinical hypothyroidism (11% vs 2%). Also, the prevalence of papillary thyroid
      cancer has been found higher in MC+HCV patients than in controls, in particular
      in patients with autoimmune thyroiditis. The involvement of T helper 1 immunity
      and chemokine (C-X-C motif) ligand 10 (CXCL10) may be the pathogenetic basis of
      the association between MC+HCV and thyroid autoimmunity. CONCLUSION: These
      results show a high prevalence of thyroid disorders in patients with MC+HCV and
      point to the need for careful monitoring of thyroid function in these patients.

PMID- 24722125
TI  - The role of Notch signaling in bone development and disease.
AB  - During the last decade a considerable amount of data have been accumulated
      regarding the role of intracellular signaling pathways in the pathogenesis of
      human diseases. One of these, Notch signaling, well known for its significance in
      cellular development and tissue morphogenesis, has been increasingly recognized
      as a crucial participant in the pathogenetic mechanisms underlying certain
      skeletal disorders. A better understanding of the biology and regulation of this
      multifaceted pathway is considered an important step towards clarification of the
      pathogenesis of various skeletal diseases and the development of novel targets
      for therapeutic purposes. 

PMID- 24722126
TI  - Bone disease in anorexia nervosa.
AB  - Anorexia nervosa is a serious psychiatric disorder accompanied by high morbidity
      and mortality. It is characterized by emaciation due to self-starvation and
      displays a unique hormonal profile. Alterations in gonadal axis, growth hormone
      resistance with low insulin-like growth factor I levels, hypercortisolemia and
      low triiodothyronine levels are almost universally present and constitute an
      adaptive response to malnutrition. Bone metabolism is likewise affected resulting
      in low bone mineral density, reduced bone accrual and increased fracture risk.
      Skeletal deficits often persist even after recovery from the disease with serious
      implications for future skeletal health. The pathogenetic mechanisms underlying
      bone disease are quite complicated and treatment is a particularly challenging
      task. 

PMID- 24722127
TI  - Sleep quality in patients with primary aldosteronism.
AB  - OBJECTIVE: In subjects at high risk for sleep apnea (SA), aldosterone
      concentrations correlate with severity of SA and primary aldosteronism (PA) is
      very often diagnosed. Patients with PA show a high prevalence of SA. Treatment of
      PA either by adrenalectomy (ADX) or mineralocorticoid receptor (MR) blockade is
      thought to abolish the increased comorbidities. However, no data are available
      regarding effectiveness of different PA treatments on quality of sleep. DESIGN:
      This prospective multi-center study included 15 patients with newly diagnosed PA
      evaluated before and 0.7 +/- 0.2 years after treatment initiation, and a second
      cohort including 81 patients who were evaluated 5.3 and 6.8 years after treatment
      initiation. Biochemical parameters, 24h blood pressure and three validated self
      assessment questionnaires (Giessen Complaint List (GBB-24), Epworth Sleepiness
      Scale (ESS) and Pittsburgh Sleep Quality-Index (PSQI)) were analyzed. RESULTS: Z
      scores of exhaustion tendency of GBB significantly improved in newly diagnosed PA
      patients after treatment initiation (1.8 +/- 1.4 vs. 1.0 +/- 1.2, p=0.034). In
      the second cohort no differences were found in GBB-24, ESS and PSQI. No
      differences were found in all three questionnaires independently of type of PA
      therapy. However, female patients scored significantly higher than males in the
      PSQI (8.7 +/- 3.6 vs 5.7 +/- 4.2, p<0.005), indicating lower sleep quality,
      independently of the type of therapy. CONCLUSIONS: For the first time, we
      analyzed quality of sleep in patients with PA, demonstrating that therapy
      initiation improves exhaustion tendency. Surprisingly, female PA patients showed
      significantly more sleep disturbances than male PA patients several years after
      treatment initiation.

PMID- 24722128
TI  - Impact of dietary modification of advanced glycation end products (AGEs) on the
      hormonal and metabolic profile of women with polycystic ovary syndrome (PCOS).
AB  - OBJECTIVE: To investigate the impact of dietary intervention on Advanced
      Glycation End products (AGEs) intake on the hormonal and metabolic profile in
      women with polycystic ovary syndrome (PCOS). METHODS: After baseline evaluation,
      23 women with PCOS [mean +/- SD, age: 23.4 +/- 5.7 years; body mass index (BMI):
      26 +/- 5.7 kg/m2] underwent the following consecutive 2-month dietary regimens: a
      hypocaloric diet with ad-libitum AGEs content (Hypo), an isocaloric diet with
      high AGEs (HA) and an isocaloric diet with low AGEs (LA). Metabolic, hormonal and
      oxidative stress status was assessed and AGEs levels were determined in all
      subjects after the completion of each dietary intervention. RESULTS: Serum levels
      of AGEs, testosterone, oxidative stress, insulin and HOMA-IR index were
      significantly increased on the HA compared to the Hypo diet and subsequently
      decreased on the LA diet (compared to HA) (p<0.05 for all parameters). BMI
      remained unaltered throughout the HA and LA periods compared to the Hypo period.
      Serum AGEs were strongly correlated with insulin, as well as with HOMA, during
      the LA dietary period (r=0.53, p=0.02 and r=0.51, p=0.03, respectively). For the
      same period, dietary AGEs were correlated with insulin levels (rho=0.49, p=0.04).
      CONCLUSIONS: Modifications of dietary AGEs intake are associated with parallel
      changes in serum AGEs, metabolic, hormonal and oxidative stress biomarkers in
      women with PCOS. These novel findings support recommendations for a low AGEs
      dietary content along with lifestyle changes in women with PCOS.

PMID- 24722129
TI  - Identification of four novel mutations in the thyroid hormone receptor-beta gene
      in 164 Spanish and 2 Greek patients with resistance to thyroid hormone.
AB  - OBJECTIVE: The aim of the study was to describe the clinical, biochemical, and
      genetic features of a sample of Mediterranean patients with RTH (resistance to
      thyroid hormone) due to mutations in TRbeta (thyroid hormone receptor beta)
      referred to our institution during the last 15 years. DESIGN: 166 blood samples
      were received for RTH genetic testing between January 1997 and December 2011.
      Genetic testing was performed by PCR amplification followed by sequencing of
      exons 7, 8, 9, and 10. Clinical and biochemical features were obtained from
      available information sent by referring hospitals. RESULTS: Mutations were
      identified in 50 patients (29 probands and 21 relatives). 64% were women, and
      mean +/- stdev age at diagnosis among probands was 33.2 +/- 20.5 years. The
      following clinical features were recorded: goiter in 50%, hyperkinetic behavior
      in 32%, and tachycardia in 29%. Up to 19% of the probands had undergone some type
      of thyroidal ablative therapy before diagnosis. As for biochemical features, mean
      +/- stdev TSH was 10.2 +/- 21.4 mUI/L, and mean +/- stdev fT4 was 35.5 +/- 10.8
      pmol/L. We found four new mutations: p.Phe451Leu, p.Pro452Arg, p.Glu457Gly, and
      p.Phe459Leu. CONCLUSIONS: The clinical and biochemical characteristics of our
      samples of Mediterranean populations with RTH were similar to those described in
      the published literature. Interestingly, in our populations we have identified
      four novel mutations in the TRbeta gene.

PMID- 24722130
TI  - The AGT and the GNB3 polymorphisms and insulin resistance in prehypertension.
AB  - OBJECTIVE: This study surveyed the frequencies of single nucleotide polymorphisms
      (SNPs) M235T AGT and C825T GNB3, and their association with insulin resistance,
      other biochemical markers and qualitative variables in subjects with high normal
      blood pressure and/or prehypertension in the Greek population. DESIGN: 330 men
      and women of Greek origin were divided into 3 groups: a) hypertensive, b)
      prehypertensive and c) control group. These groups were genetically tested for
      these polymorphisms and insulin resistance with the HOMA index. RESULTS: No
      statistically significant differences were found among the polymorphisms of the
      compared groups. However, the ? allele carriers (CT/TT vs. CC) of the C825T
      polymorphism were associated with an increased BMI in all 3 groups (p=0.004). The
      HOMA index was higher in the hypertensive (p=0.006) and prehypertensive (p=0.016)
      versus the control group, and similar results were found for insulin
      (hypertensive vs. control p=0.012, prehypertensive vs. control p=0.001) without
      statistical significance between the first 2 groups (p=0.522). Additionally,
      there was a statistically significant difference between the control group and
      the hypertensive and prehypertensive groups regarding cholesterol (control vs.
      hypertensive p=0.001, control vs. prehypertension p=0.018) and triglycerides
      (control vs. hypertensive p=0.0001, control vs. prehypertension p=0.007).
      Differences were also noted between the control and the hypertensive group
      regarding the value of HDL (p=0.005) and LDL (p=0.013). CONCLUSION: This study
      failed to demonstrate a correlation between specific SNPs, blood pressure and
      insulin resistance in the 3 groups. However, T allele carriers of the
      polymorphism C825T were found to have an increased BMI. Similarly, increased
      insulin resistance and lipidemia were more common in the hypertensive and
      prehypertensive populations.

PMID- 24722131
TI  - First trimester maternal BMI is a positive predictor of cord blood c-peptide
      levels while maternal visfatin levels is a negative predictor of birth weight.
AB  - OBJECTIVE: The role of first trimester maternal body mass index (BMI) and
      adipocytokines in cord blood c-peptide and birth weight in pregnancy was
      investigated. DESIGN: Seventy non-diabetic pregnant Caucasian women were
      recruited. Anthropometry and measurements of fasting adipocytokines (visfatin,
      leptin, adiponectin), insulin and glucose were performed in each of the three
      trimesters. At birth, birth weight and cord blood c-peptide, glucose, insulin,
      visfatin, leptin, adiponectin and IL6 in each neonate were measured. RESULTS:
      First trimester maternal BMI correlated positively with cord blood c-peptide
      (p=0.035, r=0.74) and negatively with cord blood visfatin (p=0.049, r=-0.67).
      First trimester HOMAR was negatively correlated with cord blood visfatin
      (p=0.037, r=-0.90) and negatively with cord blood leptin (p=0.031, r=0.90). First
      trimester maternal BMI was a positive predictor of cord blood c-peptide
      (p=0.007). First trimester maternal visfatin levels were negative predictors of
      birth weight (p=0.017). CONCLUSIONS: We conclude that first trimester maternal
      BMI and serum visfatin seem to be strongly associated with fetal insulin
      secretion and final birth weight, respectively, suggesting a role of early
      pregnancy maternal adipose tissue in the pregnancy metabolic environment.

PMID- 24722132
TI  - Diagnostic features and outcome of surgical therapy of acromegalic patients:
      experience of the last three decades.
AB  - OBJECTIVE: Transsphenoidal (TNS) surgery remains the primary therapeutic option
      for GH-secreting pituitary adenomas. The aims of this study were to verify the
      impact of TNS surgery on treatment of acromegaly before and after identification
      by a dedicated neurosurgical team and to enumerate diagnostic features of the
      disease described over three decades. DESIGN: 41 patients (group A) who underwent
      TNS surgery by a dedicated neurosurgical team (2000-2008) and 126 patients (group
      B) operated on by surgeons not specialized in pituitary surgery (1979-1999) were
      retrospectively analyzed. RESULTS: No significant differences were observed
      between the two groups in terms of delay of diagnosis, mean basal GH levels and
      GH nadir values, prevalence of hypopituitarism and hypertension. IGF-I SDS were
      significantly higher, while prevalence of IGT/diabetes was significantly lower in
      group B than in group A. Overall remission rate after surgery was 58.5% for group
      A (75% in microadenomas and 48% in macroadenomas, P=NS) and 37% for group B
      (P<0.05 vs group A; for microadenomas, 34% vs 75% of group A, P<0.05, for
      macroadenomas, 36% vs 48% of group A, P=NS). The mean delay of diagnosis was 4.9
      and 5.9 years in group A and B, respectively. CONCLUSIONS: Our data confirm that
      a dedicated neurosurgical team is needed in order to improve remission rates in
      acromegalic patients. No changes in biochemical, clinical and neuroradiological
      presentation of disease were observed over the last three decades. As the high
      prevalence of macroadenomas negatively influences surgical cure, earlier
      diagnosis should be considered as mandatory to achieve a better outcome.

PMID- 24722133
TI  - Effects of testosterone and estradiol on stress-induced adrenal and hippocampal
      weight changes in female rats.
AB  - OBJECTIVE: To examine the impact of circulating testosterone (T) and the
      T/Estradiol (T/Ediol) ratio on chronic stress-induced changes of adrenal and
      hippocampal weight during proestrus (PE) and estrus (E) in female rats. DESIGN:
      Stress was composed of repeated vaginal smear screening (VSS) and measured by the
      emotional reactivity score (ERS). Adrenal and hippocampal weight and the T, Ediol
      and T/Ediol ratio were assessed in PE and E controls as well as 20 h after sham
      or left adrenalectomy performed on diestrus-2 (DE-2) and PE, respectively. T was
      measured in ovariectomized (OVX) rats treated with estradiol benzoate (EB) or
      vehicle (VEH) and in non-OVX EB-treated rats. RESULTS: In OVX rats EB treatment
      increased adrenal weight and T levels. After separation of VEH- and EB-treated
      rats into the low and high T-range (below and above the mean, respectively), it
      was observed that higher T was accompanied by higher adrenal weight in EB-
      compared to VEH-treated rats only in the low T-range. Non-OVX EB-treated rats
      with high T had lower adrenal weight compared to low T. Cycling rats assigned to
      the high T-range presented higher T/Ediol ratio but similar ERS and Ediol levels
      compared to rats in the low T-range, and were characterized by reduced adrenal
      weight, higher hippocampal weight and prevalence of PE versus E. CONCLUSIONS:
      High T and high T/Ediol ratios are prominent in PE compared to E and exert a
      protective effect on hippocampal neuronal degeneration after similar chronic
      stress through T-mediated lessening of stress response thus counteracting the
      stress-promoting effects of Ediol.

PMID- 24722134
TI  - Gonadotropin secreting pituitary adenoma associated with erythrocytosis: case
      report and literature review.
AB  - BACKGROUND: Most pituitary adenomas with FSH- or LH-positive immunohistochemistry
      are endocrinologically silent, and neurological symptoms due to their large
      volume are the first clinical signs; they are rarely reported to be secreting
      gonadotropins, this usually occurring in cases with clinical endocrine findings.
      Gonadotropinomas are often treated surgically because they are unresponsive to
      conventional medical therapies. Temozolomide was recently recommended for non
      responder aggressive pituitary adenoma management. CASE REPORT: A 43-year-old
      male with a history of 5 years of erythrocytosis presented with severe headache,
      orthostatic dizziness, and difficulty walking. MRI documented a giant pituitary
      adenoma and high uptake of 111In-pentetreotide indicated somatostatin receptor
      (SSR) expression. Biochemical tests revealed a secreting gonadotropinoma. Therapy
      with somatostatin analogs and dopamine agonists improved the patient's headache,
      achieved partial hormone control, slightly reduced the size of the adenoma, and
      controlled erythrocytosis. Six months after the diagnosis, hormone escape
      occurred despite therapy, thus neurosurgery was performed. After the procedure
      the patient died of untreatable intracranial hypertension. The surgical specimen
      revealed SSR 2 and 3 expression, and temozolomide did not induce apoptosis in
      primary cell culture. REVIEW OF LITERATURE: Among gonadotropinomas, female gender
      (77%), macroadenoma (84%), young age at diagnosis (28 +/- 12 years), delay from
      first symptoms to diagnosis (up to 15 years), and ovarian cysts/menstrual
      disorders in females or macro-orchidism in males were the foremost clinical and
      neuroimaging features. CONCLUSIONS: Male gonadotropin-secreting pituitary
      adenomas may have a variable clinical expression secondary to testosterone
      excess. Somatostatin analogs, dopamine agonists or temozolomide may have a role
      that needs to be assessed case by case.

PMID- 24722135
TI  - Cushing's syndrome due to an ACTH-producing primary ovarian carcinoma.
AB  - Although Cushing's syndrome has been described in association with various
      neuroendocrine tumors producing ectopic adrenocorticotropin (ACTH), primary
      ovarian carcinoma rarely causes this syndrome. We hereby report the case of a 61
      year-old woman presented with abdominal distension, facial swelling and skin
      pigmentation. Clinical and diagnostic evaluation revealed a right ovarian tumor
      with hypercortisolemia, high plasma ACTH, extremely high plasma ACTH precursors
      and lack of dexamethasone suppression. Removal of the tumor led to normalization
      of ACTH, ACTH precursors and cortisol levels. In addition, hypokalemia,
      hyperglycemia and elevated serum CA 125 were noted, which were also normalized
      after resection of the tumor. Histopathological examination indicated a primary
      ovarian carcinoma with a mixed pattern of differentiation. Immunohistochemistry
      showed immunoreactivity for chromogranin A, synaptophysin and ACTH. Hence, the
      diagnosis of Cushing's syndrome arising from an ovarian carcinoma secreting
      ectopic ACTH was made. The case was managed successfully, with subsequent good
      recovery and no evidence of recurrence at 4 years of follow-up. 

PMID- 24722136
TI  - X-linked adrenoleukodystrophy: are signs of hypogonadism always due to testicular
      failure?
AB  - We present the clinical and hormonal findings of a young male with X-linked
      adrenoleukodystrophy (X-ALD), with special emphasis on the biochemical and
      clinical pattern of hypogonadism. A patient, with primary adrenal insufficiency
      since the age of 5 years, developed progressive neurological symptoms at the age
      of 29. Diagnosis of X-ALD was established by elevated serum very long chain fatty
      acids (VLCFAs) and genetic testing. His sexual body hair was sparse. Hormonal
      investigations revealed normal testosterone and inappropriately elevated LH
      levels. Androgen receptor gene analysis was negative for mutations or polymorphic
      variants associated with decreased receptor activity. Signs of hypogonadism in
      patients with confirmed X-ALD are not exclusively due to primary testicular
      failure. Tissue specific androgen resistance represents an alternative
      possibility. Since no loss-of-function mutations were detected in the androgen
      receptor, it is speculated that the patient's androgen resistance could be part
      of a functional defect mediated through VLCFA accumulation at the testosterone
      receptor and/or post-receptor levels. 

PMID- 24722137
TI  - When genotype prevails: sexual female-to-male transformation in classical
      antiquity, recorded by Gaius Plinius Secundus and Phlegon.
AB  - Cases of sexual reassignment in classical antiquity, namely a female-to-male
      gender change occurring after childhood, are described in the literature. Textual
      evidence concerning these cases of androgynism and their symbolism as well as a
      comprehensive scholar analysis is provided in the present study. MUedical
      interpretation of these cases covers the entire spectrum of differential
      diagnosis of heterosexual puberty in pseudohermaphrodites characterized by
      genital ambiguity.

PMID- 24722138
TI  - Effect of different seasonal strength training protocols on circulating androgen
      levels and performance parameters in professional soccer players.
AB  - OBJECTIVE: To examine the effects of three seasonal training programs, largely
      different in strength volume, on androgen levels and performance parameters in
      soccer players. DESIGN: Sixty-seven soccer players, members of three different
      professional teams, participated in the study. Strength intensity of the training
      programs were assessed as high (for Team-A, n=23), moderate (for Team-B, n=22),
      and low (for Team-C, n=22). Blood samples were analyzed for total-testosterone,
      free-testosterone, and the metabolic product of activate testosterone 3a
      androstendiol glucuronade (3a-Diol-G). Players were tested for maximal oxygen
      consumption (VO2max), squad-jump (SJ), countermovement-jump (CMJ), 10 m and 20 m
      sprint performance prior at the beginning of the pre-season period, at the middle
      (mid-point), and at the end of the competition period (end-point). RESULTS: All
      performance parameters increased significantly until mid-point in all teams
      (p<0.001). However, performance was further increased only in Team-A only for
      jumping and sprinting ability between end-point vs mid-point (p<0.001). An effect
      of the training program of Team-A on TT levels was evident exhibiting significant
      differences between at all point-measurements (baseline/mid-point:p=0.024,
      baseline/end-point:p<0.001, mid/end-point:p=0.008), while a marginally
      significant effect (p=0.051) was detected within Team-B and a non-significant
      effect in Team-C. Similar results were obtained for 3a-Diol-G in Team-A (p=0.001)
      where significant differences were found between end-point to both baseline
      (p=0.001) and mid-point (p=0.038). No differences were detectable for FT. A
      borderline significant negative correlation was observed between 3a-Diol-G and
      VO2max in Team-B at mid-point. No other correlations were evident between
      performance and hormonal parameters. CONCLUSION: Our findings suggest that the
      volume of strength training combined with intensive soccer training caused an
      elevation of circulating TT and 3a-Diol-G levels in parallel to the induction of
      performance capacity. It is our opinion that the elevation of endogenous
      androgens as a result of the volume of strength training indicates that the only
      method to improve athletic performance is hard training. There are no substitutes
      or shortcuts. If the organism needs more androgens it will produce them
      endogenously.

PMID- 24722140
TI  - Sensitivity analysis of CLIMEX parameters in modeling potential distribution of
      Phoenix dactylifera L.
AB  - Using CLIMEX and the Taguchi Method, a process-based niche model was developed to
      estimate potential distributions of Phoenix dactylifera L. (date palm), an
      economically important crop in many counties. Development of the model was based
      on both its native and invasive distribution and validation was carried out in
      terms of its extensive distribution in Iran. To identify model parameters having
      greatest influence on distribution of date palm, a sensitivity analysis was
      carried out. Changes in suitability were established by mapping of regions where
      the estimated distribution changed with parameter alterations. This facilitated
      the assessment of certain areas in Iran where parameter modifications impacted
      the most, particularly in relation to suitable and highly suitable locations.
      Parameter sensitivities were also evaluated by the calculation of area changes
      within the suitable and highly suitable categories. The low temperature limit
      (DV2), high temperature limit (DV3), upper optimal temperature (SM2) and high
      soil moisture limit (SM3) had the greatest impact on sensitivity, while other
      parameters showed relatively less sensitivity or were insensitive to change. For
      an accurate fit in species distribution models, highly sensitive parameters
      require more extensive research and data collection methods. Results of this
      study demonstrate a more cost effective method for developing date palm
      distribution models, an integral element in species management, and may prove
      useful for streamlining requirements for data collection in potential
      distribution modeling for other species as well. 

PMID- 24722139
TI  - Intensive-phase treatment outcomes among hospitalized multidrug-resistant
      tuberculosis patients: results from a nationwide cohort in Nigeria.
AB  - BACKGROUND: Nigeria is faced with a high burden of Human Immunodeficiency Virus
      (HIV) infection and multidrug-resistant tuberculosis (MDR-TB). Treatment outcomes
      among MDR-TB patients registered across the globe have been poor, partly due to
      high loss-to-follow-up. To address this challenge, MDR-TB patients in Nigeria are
      hospitalized during the intensive-phase(IP) of treatment (first 6-8 months) and
      are provided with a package of care including standardized MDR-TB treatment
      regimen, antiretroviral therapy (ART) and cotrimoxazole prophylaxis (CPT) for HIV
      infected patients, nutritional and psychosocial support. In this study, we report
      the end-IP treatment outcomes among them. METHODS: In this retrospective cohort
      study, we reviewed the patient records of all bacteriologically-confirmed MDR-TB
      patients admitted for treatment between July 2010 and October 2012. RESULTS: Of
      162 patients, 105(65%) were male, median age was 34 years and 28(17%) were HIV
      infected; all 28 received ART and CPT. Overall, 138(85%) were alive and culture
      negative at the end of IP, 24(15%) died and there was no loss-to-follow-up.
      Mortality was related to low CD4-counts at baseline among HIV-positive patients.
      The median increase in body mass index among those documented to be underweight
      was 2.6 kg/m2 (p<0.01) and CD4-counts improved by a median of 52 cells/microL
      among the HIV-infected patients (p<0.01). CONCLUSIONS: End-IP treatment outcomes
      were exceptional compared to previously published data from international
      cohorts, thus confirming the usefulness of a hospitalized model of care. However,
      less than five percent of all estimated 3600 MDR-TB patients in Nigeria were
      initiated on treatment during the study period. Given the expected scale-up of
      MDR-TB care, the hospitalized model is challenging to sustain and the national TB
      programme is contemplating to move to ambulatory care. Hence, we recommend using
      both ambulatory and hospitalized approaches, with the latter being reserved for
      selected high-risk groups.

PMID- 24722142
TI  - Spectroscopic detection and state preparation of a single praseodymium ion in a
      crystal.
AB  - The narrow optical transitions and long spin coherence times of rare earth ions
      in crystals make them desirable for a number of applications ranging from solid
      state spectroscopy and laser physics to quantum information processing. However,
      investigations of these features have not been possible at the single-ion level.
      Here we show that the combination of cryogenic high-resolution laser spectroscopy
      with optical microscopy allows one to spectrally select individual praseodymium
      ions in yttrium orthosilicate. Furthermore, this spectral selectivity makes it
      possible to resolve neighbouring ions with a spatial precision of the order of 10
      nm. In addition to elaborating on the essential experimental steps for achieving
      this long-sought goal, we demonstrate state preparation and read out of the three
      ground-state hyperfine levels, which are known to have lifetimes of the order of
      hundred seconds.

PMID- 24722141
TI  - Functional analysis of a missense mutation in the serine protease inhibitor
      SPINT2 associated with congenital sodium diarrhea.
AB  - Membrane-bound serine proteases play important roles in different biological
      processes. Their regulation by endogenous inhibitors is poorly understood. A
      Y163C mutation in the SPINT2 gene encoding the serine protease inhibitor
      Hepatocyte Growth Factor Inhibitor HAI-2 is associated with a congenital sodium
      diarrhea. The functional consequences of this mutation on HAI-2 activity and its
      physiological targets are unknown. We established a cellular assay in Xenopus
      laevis oocytes to study functional interactions between HAI-2 and candidate
      membrane-bound serine proteases expressed in the gastro-intestinal tract. We
      found that the wild-type form of HAI-2 is a potent inhibitor of nine gastro
      intestinal serine proteases. The Y163C mutation in the second Kunitz domain of
      HAI-2 resulted in a complete loss of inhibitory activity on two intestinal
      proteases, prostasin and tmprss13. The effect of the mutation of the homologous
      Y68C in the first Kunitz domain of HAI-2 is consistent with a differential
      contribution of the two Kunitz domains of HAI-2 in the inhibition of serine
      proteases. By contrast to the Tyr to Cys, the Tyr to Ser substitution did not
      change the inhibitory potency of HAI-2, indicating that the thiol-group of the
      cysteine rather than the Tyr deletion is responsible for the HAI-2 loss of
      function. Our functional assay allowed us to identify membrane-bound serine
      proteases as cellular target for inhibition by HAI-2 wild type and mutants, and
      to better define the role of the Tyr in the second Kunitz domain in the
      inhibitory activity of HAI-2. 

PMID- 24722143
TI  - Use of targeted exome sequencing in genetic diagnosis of Chinese familial
      hypercholesterolemia.
AB  - Familial hypercholesterolemia is an autosomal dominant inherited disease
      characterized by elevated plasma low-density lipoprotein cholesterol (LDL-C). It
      is mainly caused by mutations of the low-density lipoprotein receptor (LDLR)
      gene. Currently, the methods of whole genome sequencing or whole exome sequencing
      for screening mutations in familial hypercholesterolemia are not applicable in
      China due to high cost. We performed targeted exome sequencing of 167 genes
      implicated in the homozygous phenotype of a proband pedigree to identify
      candidate mutations, validated them in the family of the proband, studied the
      functions of the mutant protein, and followed up serum lipid levels after
      treatment. We discovered that exon 9 c.1268 T>C and exon 8 c.1129 T>G compound
      heterozygous mutations in the LDLR gene in the proband derived from the mother
      and father, respectively, in which the mutation of c.1129 T>G has not been
      reported previously. The mutant LDL-R protein had 57% and 52% binding and
      internalization functions, respectively, compared with that of the wild type.
      After 6 months of therapy, the LDL-C level of the proband decreased by more than
      50% and the LDL-C of the other family members with heterozygous mutation also
      reduced to normal. Targeted exome sequencing is an effective method for screening
      mutation genes in familial hypercholesterolemia. The exon 8 and 9 mutations of
      the LDLR gene were pedigree mutations. The functions of the mutant LDL-R protein
      were decreased significantly compared with that of the wild type. Simvastatin
      plus ezetimibe was proven safe and effective in this preschool-age child. 

PMID- 24722145
TI  - Highly electrically conductive nanocomposites based on polymer-infused graphene
      sponges.
AB  - Conductive polymer composites require a three-dimensional 3D network to impart
      electrical conductivity. A general method that is applicable to most polymers for
      achieving a desirable graphene 3D network is still a challenge. We have developed
      a facile technique to fabricate highly electrical conductive composite using
      vacuum-assisted infusion of epoxy into graphene sponge GS scaffold. Macroscopic
      GSs were synthesized from graphene oxide solution by a hydrothermal method
      combined with freeze drying. The GS/epoxy composites prepared display consistent
      isotropic electrical conductivity around 1 S/m, and it is found to be close to
      that of the pristine GS. Compared with neat epoxy, GS/epoxy has a 12-orders-of
      magnitude increase in electrical conductivity, attributed to the compactly
      interconnected graphene network constructed in the polymer matrix. This method
      can be extended to other materials to fabricate highly conductive composites for
      practical applications such as electronic devices, sensors, actuators, and
      electromagnetic shielding.

PMID- 24722144
TI  - The influence of sex steroid hormones in the immunopathology of experimental
      pulmonary tuberculosis.
AB  - The relation between men and women suffering pulmonary tuberculosis is 7/3 in
      favor to males. Sex hormones could be a significant factor for this difference,
      considering that testosterone impairs macrophage activation and pro-inflammatory
      cytokines production, while estrogens are proinflammatory mediator's inducer. The
      aim of this work was to compare the evolution of tuberculosis in male and female
      mice using a model of progressive disease. BALB/c mice, male and female were
      randomized into two groups: castrated or sham-operated, and infected by the
      intratracheal route with a high dose of Mycobacterium tuberculosis strain H37Rv.
      Mice were euthanized at different time points and in their lungs were determined
      bacilli loads, inflammation, cytokines expression, survival and testosterone
      levels in serum. Non-castrated male mice showed significant higher mortality and
      bacilli burdens during late disease than female and castrated male animals.
      Compared to males, females and castrated males exhibited significant higher
      inflammation in all lung compartments, earlier formation of granulomas and
      pneumonia, while between castrated and non-castrated females there were not
      significant differences. Females and castrated males expressed significant higher
      TNF-alpha, IFN gamma, IL12, iNOS and IL17 than non-castrated males during the
      first month of infection. Serum Testosterone of males showed higher concentration
      during late infection. Orchidectomy at day 60 post-infection produced a
      significant decrease of bacilli burdens in coexistence with higher expression of
      TNFalpha, IL-12 and IFNgamma. Thus, male mice are more susceptible to
      tuberculosis than females and this was prevented by castration suggesting that
      testosterone could be a tuberculosis susceptibility factor. 

PMID- 24722146
TI  - Antinociceptive effect of tetrandrine on LPS-induced hyperalgesia via the
      inhibition of IKKbeta phosphorylation and the COX-2/PGE2 pathway in mice.
AB  - Tetrandrine (TET) is a bisbenzylisoquinoline alkaloid that is isolated from the
      Stephania Tetrandra. It is known to possess anti-inflammatory and
      immunomodulatory effects. We have shown that TET can effectively suppress the
      production of bacterial lipopolysaccharide (LPS)-induced inflammatory mediators,
      including cyclooxygenases (COXs), in macrophages. However, whether TET has an
      antinociceptive effect on LPS-induced hyperalgesia is unknown. In the present
      study, we investigated the potential antinociceptive effects of TET and the
      mechanisms by which it elicits its effects on LPS-induced hyperalgesia. LPS
      effectively evoked hyperalgesia and induced the production of PGE2 in the sera,
      brain tissues, and cultured astroglia. TET pretreatment attenuated all of these
      effects. LPS also activated inhibitor of kappaB (IkappaB) kinase beta (IKKbeta)
      and its downstream components in the IkappaB/nuclear factor (NF)-kappaB signaling
      pathway, including COX-2; the increase in expression levels of these components
      was significantly abolished by TET. Furthermore, in primary astroglia, knockdown
      of IKKbeta, but not IKKalpha, reversed the effects of TET on the LPS-induced
      increase in IkappaB phosphorylation, P65 phosphorylation, and COX-2. Our results
      suggest that TET can effectively exert antinociceptive effects on LPS-induced
      hyperalgesia in mice by inhibiting IKKbeta phosphorylation, which leads to the
      reduction in the production of important pain mediators, such as PGE2 and COX-2,
      via the IKKbeta/IkappaB/NF-kappaB pathway.

PMID- 24722148
TI  - Breaking down RET breakpoints in lung adenocarcinoma.

PMID- 24722149
TI  - ALK testing in non-small cell lung carcinoma: what now?

PMID- 24722150
TI  - ITMIG consensus statement on the use of the WHO histological classification of
      thymoma and thymic carcinoma: refined definitions, histological criteria, and
      reporting.
AB  - INTRODUCTION: The 2004 version of the World Health Organization classification
      subdivides thymic epithelial tumors into A, AB, B1, B2, and B3 (and rare other)
      thymomas and thymic carcinomas (TC). Due to a morphological continuum between
      some thymoma subtypes and some morphological overlap between thymomas and TC, a
      variable proportion of cases may pose problems in classification, contributing to
      the poor interobserver reproducibility in some studies. METHODS: To overcome this
      problem, hematoxylin-eosin-stained and immunohistochemically processed sections
      of prototypic, "borderland," and "combined" thymomas and TC (n = 72) were studied
      by 18 pathologists at an international consensus slide workshop supported by the
      International Thymic Malignancy Interest Group. RESULTS: Consensus was achieved
      on refined criteria for decision making at the A/AB borderland, the distinction
      between B1, B2, and B3 thymomas and the separation of B3 thymomas from TCs.
      "Atypical type A thymoma" is tentatively proposed as a new type A thymoma
      variant. New reporting strategies for tumors with more than one histological
      pattern are proposed. CONCLUSION: These guidelines can set the stage for
      reproducibility studies and the design of a clinically meaningful grading system
      for thymic epithelial tumors.

PMID- 24722151
TI  - National patterns of care and outcomes after combined modality therapy for stage
      IIIA non-small-cell lung cancer.
AB  - INTRODUCTION: The role of surgery in addition to chemotherapy and radiation for
      stage IIIA non-small-cell lung cancer (NSCLC) remains controversial. Because
      there are limited data on the benefit from surgery in this setting, we evaluated
      the use of combined modality therapy nationally and explored the outcomes with
      and without the addition of surgery. METHODS: Patient variables and treatment
      related outcomes were abstracted for patients with clinical stage IIIA NSCLC from
      the National Cancer Database. Patients receiving chemotherapy and radiation were
      compared with those undergoing chemotherapy, radiation, and surgery (CRS) in any
      sequence. RESULTS: Between 1998 and 2010, 61,339 patients underwent combined
      modality treatment for clinical stage IIIA NSCLC. Of these, 51,979 (84.7%)
      received chemotherapy and radiation while 9360 (15.3%) underwent CRS. Patients in
      the CRS group were younger, more likely female patients and Caucasians, and had
      smaller tumors and lower Charlson comorbidity scores. The 30-day surgical
      mortality was 200 of 8993 (2.2%). The median overall survival favored the CRS
      group in both unmatched (32.4 months versus 15.7 months, p < 0.001) and matched
      analysis based on patient characteristics (34.3 versus 18.4 months, p < 0.001).
      CONCLUSIONS: There is significant heterogeneity in the treatment of stage IIIA
      NSCLC in the United States. Patients selected for surgery in addition to
      chemoradiation therapy seem to have better long-term survival.

PMID- 24722152
TI  - Molecular mechanisms underlying oncogenic RET fusion in lung adenocarcinoma.
AB  - BACKGROUND: Oncogenic RET fusion, caused by an inversion in chromosome 10, was
      recently identified as a driver mutation for the development of lung
      adenocarcinoma (LADC). Nevertheless, the molecular mechanism(s) underlying the
      rearrangement of the RET locus during lung carcinogenesis are unknown. METHODS:
      Genomic segments containing breakpoint junctions for RET fusions were cloned and
      analyzed by genomic polymerase chain reaction and genome capture sequencing using
      a next-generation sequencer to identify the mechanisms involved in DNA strand
      breaks and illegitimate joining of DNA ends. Of the 18 cases studied, 16 were
      identified by screening 671 LADC cases and two were previously published.
      RESULTS: Almost all (17 of 18, 94%) of the breakpoints in RET were located within
      a 2.0-kb region spanning exon 11 to intron 11 and no breakpoint occurred within 4
      bp of any other. This suggested that as in papillary thyroid carcinoma, DNA
      strand breaks formed at nonspecific sites within this region trigger RET fusion.
      Just over half of the RET fusions in LADC (10 of 18, 56%) were caused by simple
      reciprocal inversion, and two DNA-repair mechanisms, namely nonhomologous end
      joining and break-induced replication, were deduced to have contributed to the
      illegitimate joining of the DNA ends. CONCLUSIONS: Oncogenic RET fusion in LADC
      occurs through multiple pathways and involves the illegitimate repair of DNA
      strand breaks through mechanisms different from those identified in papillary
      thyroid carcinoma, where RET fusion also functions as a driver mutation.

PMID- 24722153
TI  - An international interpretation study using the ALK IHC antibody D5F3 and a
      sensitive detection kit demonstrates high concordance between ALK IHC and ALK
      FISH and between evaluators.
AB  - INTRODUCTION: The goal of personalized medicine is to treat patients with a
      therapy predicted to be efficacious based on the molecular characteristics of the
      tumor, thereby sparing the patient futile or toxic therapy. Anaplastic lymphoma
      kinase (ALK) inhibitors are effective against ALK-positive non-small-cell lung
      cancer (NSCLC) tumors, but to date the only approved companion diagnostic is a
      break-apart fluorescence in situ hybridization (FISH) assay. Immunohistochemistry
      (IHC) is a clinically applicable cost-effective test that is sensitive and
      specific for ALK protein expression. The purpose of this study was to assemble an
      international team of expert pathologists to evaluate a new automated
      standardized ALK IHC assay. METHODS: Archival NSCLC tumor specimens (n =103)
      previously tested for ALK rearrangement by FISH were provided by the
      international collaborators. These specimens were stained by IHC with the anti
      ALK (D5F3) primary antibody combined with OptiView DAB IHC detection and OptiView
      amplification (Ventana Medical Systems, Inc., Tucson, AZ). Specimens were scored
      binarily as positive if strong granular cytoplasmic brown staining was present in
      tumor cells. IHC results were compared with the FISH results and interevaluator
      comparisons made. RESULTS: Overall for the 100 evaluable cases the ALK IHC assay
      was highly sensitive (90%), specific (95%), and accurate relative (93%) to the
      ALK FISH results. Similar results were observed using a majority score. IHC
      negativity was scored by seven of seven and six of seven evaluators on three and
      two FISH-positive cases, respectively. IHC positivity was scored on two FISH
      negative cases by seven of seven readers. There was agreement among seven of
      seven and six of seven readers on 88% and 96% of the cases before review,
      respectively, and after review there was agreement among seven of seven and six
      of seven on 95% and 97% of the cases, respectively. CONCLUSIONS: On the basis of
      expert evaluation the ALK IHC test is sensitive, specific, and accurate, and a
      majority score of multiple readers does not improve these results over an
      individual reader's score. Excellent inter-reader agreement was observed. These
      data support the algorithmic use of ALK IHC in the evaluation of NSCLC.

PMID- 24722154
TI  - High MET receptor expression but not gene amplification in ALK 2p23 rearrangement
      positive non-small-cell lung cancer.
AB  - INTRODUCTION: Overexpression of MET receptor tyrosine kinase and its ligand
      hepatocyte growth factor (HGF) and MET gene amplification have been well
      documented in non-small-cell lung cancer (NSCLC). Activated MET signaling plays
      an important role in human cancer tumorigenesis, metastasis, and drug resistance.
      However, the deregulation of MET/HGF pathway in NSCLC harboring ALK gene
      rearrangement (ALK[+]), which is sensitive to dual ALK and MET inhibitor
      Crizotinib, has not been reported. METHODS: We performed systematic analysis of
      MET/HGF expression by immunohistochemistry (IHC) and MET gene amplification by
      dual color, dual hapten bright field in situ hybridization in 19 ALK(+) and 73
      ALK(-) NSCLC tumor tissues from those who had clinical ALK rearrangement test
      done at the Cleveland Clinic from August 2010 to January 2013. IHC scoring was
      interpreted on a standard four-tier system. RESULTS: The percentage of MET IHC
      score 0, 1+, 2+, and 3+ were 5.5%, 27.8%, 50.0%, and 16.7% in ALK(+) group,
      compared with 28.8%, 33.9%, 23.7%, and 13.6% in ALK(-) group, respectively. The
      MET high expression (IHC score 2 or 3) was significantly higher in ALK(+) group
      statistically (66.7% versus 37.3%, p = 0.03). HGF-high expression (IHC score 2 or
      3) was 33.3% in ALK(+) and 15.8% in ALK(-) (p = 0.17). We identified eight cases
      in ALK(-) and one case in ALK(+) tumor who had MET gene amplification (18.4%
      versus 7.1%, p = 0.43) by dual color, dual hapten bright field in situ
      hybridization. No significant correlation between MET protein receptor expression
      and gene amplification was identified. CONCLUSIONS: Our study demonstrated for
      the first time that MET receptor expression, but not MET gene amplification, is
      significantly increased in ALK(+) NSCLC. MET gene amplification is a relatively
      rare event in this unique population compared with ALK(-) NSCLC.

PMID- 24722155
TI  - The clinical relevance of pathologic subtypes in metastatic lung adenocarcinoma.
AB  - INTRODUCTION: The International Association for the Study of Lung Cancer/American
      Thoracic Society/European Respiratory Society classification of lung
      adenocarcinoma recommends identification of pathologic patterns in metastatic
      samples where possible. We investigated the clinical relevance of these patterns.
      METHODS: Patients with a surgical biopsy of lung adenocarcinoma from a metastatic
      site were included. Slides were reviewed by an anatomical pathologist identifying
      the histologic patterns of solid with mucin, acinar, micropapillary, papillary,
      and assigning a major adenocarcinoma subtype according to the International
      Association for the Study of Lung Cancer/American Thoracic Society/European
      Respiratory Society classification. EGFR and KRAS mutation testing were performed
      on formalin-fixed, paraffin-embedded blocks. Mutations were detected by high
      resolution melting assay with high resolution melting-positive samples confirmed
      by Sanger sequencing. RESULTS: One-hundred patients were included. The major
      histologic subtype prevalence was as follows: solid (50), acinar (29),
      micropapillary (20), and papillary (1). Of 100 patients, 45 received no systemic
      therapy with no overall survival differences seen by histologic subtype and 55
      received systemic therapy (chemoradiotherapy with curative intent or palliative
      chemotherapy). Worse survival was seen in the major solid histologic subtype
      compared with major acinar (hazard ratio 0.32 [95% confidence interval 0.15
      0.68], p = 0.003) and micropapillary subtypes (hazard ratio 0.34 [95% confidence
      interval, 0.17-0.69], p = 0.003). The major solid histologic subtype was less
      likely to harbor EGFR mutations (p = 0.006) and was less frequent in never
      smokers (p = 0.010) compared with other histologic subtypes. CONCLUSION: The
      major solid histologic subtype of lung adenocarcinoma at metastatic sites is
      associated with shorter overall survival on systemic anticancer therapy.
      Furthermore, the major solid histologic subtype is less likely to harbor EGFR
      mutations. These results require validation in larger cohorts.

PMID- 24722156
TI  - Outcomes of unresected ground-glass nodules with cytology suspicious for
      adenocarcinoma.
AB  - BACKGROUND: Five-year survival rates for resected stage I adenocarcinoma approach
      100%. Given previous studies describing the prolonged indolent natural history of
      ground-glass lesions suspicious for early adenocarcinoma, our purpose in this
      study was to determine if outcomes were different among patients who were
      observed for radiographic and biopsy suspected early adenocarcinoma compared with
      those who were resected immediately. METHODS: We identified 63 patients with no
      prior history of lung adenocarcinoma who had undergone computer tomography-guided
      fine-needle aspiration of ground-glass opacities with cytology concerning for new
      early adenocarcinoma between January 2002 and December 2011. We compared the
      clinical outcomes of patients who were resected after abnormal cytology results
      and those who opted for watchful waiting. RESULTS: Sixteen patients elected to
      observe their ground-glass nodules despite having suspicious cytology results,
      whereas 47 opted for immediate resection. Of the 16 observed patients, six
      (37.5%) ultimately demonstrated growth or increase solid component of the ground
      glass nodule. Five of these patients elected for definitive therapy by surgical
      resection or radiation. There were no occurrences of distant metastasis or lung
      cancer-associated deaths in the observed group. Of the 47 resected patients, two
      developed metastatic disease, five developed new cancers in remaining lung, and
      three developed progression in existing ground-glass nodules. CONCLUSIONS: Ground
      glass lesions that were observed after biopsy did not demonstrate any increased
      rates of metastasis or cancer-related deaths and delayed resection does not seem
      to have a negative effect on outcomes.

PMID- 24722158
TI  - MET expression plays differing roles in non-small-cell lung cancer patients with
      or without EGFR mutation.
AB  - INTRODUCTION: Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors
      and Met inhibitors have enabled progress in the management of advanced non-small
      cell lung cancer (NSCLC). However, the clinical benefits of these agents are not
      uniform across the NSCLC spectrum. Thus, we evaluated the prognostic effect of
      mesenchymal-epithelial transition (MET) expression in Asian NSCLC patients with
      or without EGFR mutation. METHODS: Frozen tumor tissues were collected from 92
      patients with surgical resection and 10 with lymph node biopsy. Mutations in
      exons 18-21 in the EGFR-tyrosine kinase domain and MET expression were analyzed
      by using sequencing and immunohistochemistry, respectively. RESULTS: The MET
      overexpression rate was 51% in NSCLC patients. MET-positive patients had poorer
      overall survival than MET-negative patients (29.8 versus 69.1 months, chi =
      7.420, p = 0.006) in patients with wild-type EGFR. However, no statistically
      significant difference was found in EGFR mutant patients (35.0 versus 35.9
      months, chi = 0.114, p = 0.735). Multivariate analysis showed that stage, MET
      expression, and sex were independent prognostic factors in patients with wild
      type EGFR (chi = 32.896, p < 0.001). CONCLUSIONS: These results suggest that MET
      expression has different prognostic significance in patients with differing EGFR
      mutation status. Whether MET inhibitors should be given early to NSCLC patients
      with EGFR wild-type needs further investigation.

PMID- 24722157
TI  - A phase I study of concurrent individualized, isotoxic accelerated radiotherapy
      and cisplatin-vinorelbine-cetuximab in patients with stage III non-small-cell
      lung cancer.
AB  - BACKGROUND: In this open-label phase I study, the maximum-tolerated dose of
      cetuximab with concurrent chemoradiotherapy (C-CRT) in stage III non-small-cell
      lung cancer together with individualized, isotoxic accelerated radiotherapy (RT)
      was investigated. METHODS: Patients with stage III non-small-cell lung cancer,
      World Health Organization performance status 0-1, forced expiratory volume in 1
      second more than 50%, carbon monoxide diffusing capacity more than 50%, weight
      loss less than 10%, and no severe comorbidity were enrolled. Patients without
      progression after one to two cycles of gemcitabine-carboplatin were included and
      treated with cetuximab 400 mg/kg d7 and 250 mg/kg weekly together with RT and
      cisplatin (50 mg/m d1, 8; 40 mg/m d22)-vinorelbine for 5 weeks. Vinorelbine was
      escalated in three steps; (1) 10 mg/m d1, 8 and 8 mg/m d22, 29; (2) 20 mg/m d1, 8
      and 8 mg/m d22, 29; (3) 20 mg/m d1, 8; 15 mg/m d22, 29. An individualized
      prescribed RT dose based on normal tissue dose constraints was applied (e.g.,
      mean lung dose 19 Gy). The primary endpoint was the maximum-tolerated dose 3
      months after the end of C-CRT; secondary endpoints were toxicity and metabolic
      response as assessed by positron emission tomography. RESULTS: Between September
      2007 and October 2010, 25 patients (12 men, 13 women, mean age 59 years) were
      included. The mean RT dose was 62 +/- 6.6 Gy. The vinorelbine dose could be
      escalated to dose level 3. Twelve of 25 patients experienced greater than or
      equal to grade 3 toxicity (esophagitis 3, rash 1, diarrhea 1, cough 1, dyspnea 1,
      vomiting 1, and pulmonary embolism 1). No dose-limiting toxicities were observed.
      One patient with a complete pathological response in dose level 3 developed a
      fatal hemoptysis 4 months after RT. Metabolic remissions were observed in 19 of
      22 patients. CONCLUSION: C-CRT with cetuximab and cisplatin-vinorelbine is safe
      to deliver at full dose. The recommended phase II dose is therefore cetuximab 400
      mg/m d7 and 250 mg/m weekly, cisplatin 50 mg/m d1, 8; 40 mg/m d22 and vinorelbine
      20 mg/m d1, 8; 15 mg/m d22, 29 for 5 weeks together with RT.

PMID- 24722159
TI  - ALK/EML4 fusion gene may be found in pure squamous carcinoma of the lung.
AB  - INTRODUCTION: The report of cases of lung squamous cell cancers harboring
      anaplastic lymphoma kinase (ALK) gene rearrangements raises the question whether
      this histologic subtype should be also evaluated for such molecular predictive
      test. METHODS: A consecutive series of 40 lung pure squamous cell carcinomas were
      analyzed for ALK gene status by fluorescence in situ hybridization. Squamous
      differentiation was validated using an immunohistochemical panel including n-p63
      (p40), cytokeratin (CK) 5/6, sex-determining region Y (SRY)-Box2 (SOX2), thyroid
      transcription factor 1, CK7, and Napsin-A. RESULTS: Squamous differentiation was
      confirmed in all tumors as they stained positive for n-p63 and CK5/6 and negative
      for thyroid transcription factor 1 and Napsin-A. One of 40 cases (2.5%) showed an
      ALK rearrangement on fluorescence in situ hybridization analysis. CONCLUSIONS:
      ALK translocation may be found in lung pure squamous cell carcinomas. Our data
      suggest the opportunity to test ALK rearrangements on biopsy samples harboring
      squamous cell cancer differentiation.

PMID- 24722160
TI  - Phase II randomized study of vandetanib plus gemcitabine or gemcitabine plus
      placebo as first-line treatment of advanced non-small-cell lung cancer in elderly
      patients.
AB  - INTRODUCTION: The aim of the present study was to evaluate the efficacy and
      tolerability of vandetanib plus gemcitabine (V/G) compared with gemcitabine alone
      in elderly patients with untreated advanced non-small-cell lung cancer. METHODS:
      This was a phase II, randomized, double-blind study. A total of 124 elderly
      patients (mean age, 75 yr; age range, 70-84 yr; 73% men) received V/G (n = 61) or
      placebo plus gemcitabine (n = 63). Progression-free survival (PFS) was the
      primary endpoint. Secondary endpoints were overall survival, objective response
      rate, duration of response, disease control rate, time to deterioration of
      performance status, and safety outcomes. RESULTS: PFS was significantly prolonged
      with V/G (median, 183 days; 95% confidence interval, 116-214) compared with
      placebo plus gemcitabine (median, 169 days; 95% confidence interval, 95-194; p =
      0.047). No statistically significant differences between arms were observed in
      all secondary endpoints, including overall survival. The addition of vandetanib
      to gemcitabine was well tolerated. The rate of patients with >=1 treatment
      related adverse event was comparable in the two arms, pyrexia, dyspnea, and
      neutropenia being the most common adverse events. CONCLUSIONS: V/G combination
      was associated with a statistically significant prolongation of PFS compared with
      gemcitabine alone in untreated elderly patients with advanced non-small-cell lung
      cancer, with an acceptable safety profile.

PMID- 24722161
TI  - Primary osteosarcoma of rib mimicking lung mass with secondary aneurysmal bone
      cyst formation.

PMID- 24722162
TI  - Miliary brain metastases in a patient with ROS1-rearranged lung adenocarcinoma: a
      case report.

PMID- 24722163
TI  - Experience with erlotinib in lung adenocarcinoma harboring a coexisting KIF5B-RET
      fusion gene and EGFR mutation: report of a rare case.

PMID- 24722164
TI  - Dynamic social community detection and its applications.
AB  - Community structure is one of the most commonly observed features of Online
      Social Networks (OSNs) in reality. The knowledge of this feature is of great
      advantage: it not only provides helpful insights into developing more efficient
      social-aware solutions but also promises a wide range of applications enabled by
      social and mobile networking, such as routing strategies in Mobile Ad Hoc
      Networks (MANETs) and worm containment in OSNs. Unfortunately, understanding this
      structure is very challenging, especially in dynamic social networks where social
      interactions are evolving rapidly. Our work focuses on the following questions:
      How can we efficiently identify communities in dynamic social networks? How can
      we adaptively update the network community structure based on its history instead
      of recomputing from scratch? To this end, we present Quick Community Adaptation
      (QCA), an adaptive modularity-based framework for not only discovering but also
      tracing the evolution of network communities in dynamic OSNs. QCA is very fast
      and efficient in the sense that it adaptively updates and discovers the new
      community structure based on its history together with the network changes only.
      This flexible approach makes QCA an ideal framework applicable for analyzing
      large-scale dynamic social networks due to its lightweight computing-resource
      requirement. To illustrate the effectiveness of our framework, we extensively
      test QCA on both synthesized and real-world social networks including Enron,
      arXiv e-print citation, and Facebook networks. Finally, we demonstrate the
      applicability of QCA in real applications: (1) A social-aware message forwarding
      strategy in MANETs, and (2) worm propagation containment in OSNs. Competitive
      results in comparison with other methods reveal that social-based techniques
      employing QCA as a community detection core outperform current available methods.

PMID- 24722165
TI  - A unique case of bullous drug eruption related to vancomycin and cefoperazone.

PMID- 24722166
TI  - Carbon-decorated Li4Ti5O12/rutile TiO2 mesoporous microspheres with
      nanostructures as high-performance anode materials in lithium-ion batteries.
AB  - Li4Ti5O12/rutile TiO2 (LTO-RT) composites with Li/Ti molar ratios of 3:5, 4:5 and
      4.5:5 have been successfully synthesized with TiO2 microspheres as a precursor.
      Furthermore, C-coated LTO-RT mesoporous microspheres with a molar ratio of 4:5
      (C/4-5-LTO-RT) have been prepared based on the LTO-RT composite through a
      hydrothermal method and high temperature calcination. After various
      characterizations, it is found that carbon plays a pivotal role in retaining the
      porous nanostructure of the original as-prepared TiO2 precursor in the overall
      process. Substantially, C/4-5-LTO-RT still shows a high specific surface area of
      63.70 m(2) g(-1) even after high temperature treatment at 800  degrees C. Since
      the porous nanostructure offers open and direct channels for the diffusion of Li
      ions and electrons and carbon decoration also efficiently improves the electrical
      conductivity, the sample of C/4-5-LTO-RT shows an enhanced electrochemical
      performance. In addition, the presence of nanosized rutile TiO2 in C/4-5-LTO-RT
      has an important contribution to the high electrochemical performance, as does
      the fast lithium ion diffusion along the [001] direction. 

PMID- 24722167
TI  - Dynamics of cellular responses to radiation.
AB  - Understanding the consequences of exposure to low dose ionizing radiation is an
      important public health concern. While the risk of low dose radiation has been
      estimated by extrapolation from data at higher doses according to the linear non
      threshold model, it has become clear that cellular responses can be very
      different at low compared to high radiation doses. Important phenomena in this
      respect include radioadaptive responses as well as low-dose hyper
      radiosensitivity (HRS) and increased radioresistance (IRR). With radioadaptive
      responses, low dose exposure can protect against subsequent challenges, and two
      mechanisms have been suggested: an intracellular mechanism, inducing cellular
      changes as a result of the priming radiation, and induction of a protected state
      by inter-cellular communication. We use mathematical models to examine the effect
      of these mechanisms on cellular responses to low dose radiation. We find that the
      intracellular mechanism can account for the occurrence of radioadaptive
      responses. Interestingly, the same mechanism can also explain the existence of
      the HRS and IRR phenomena, and successfully describe experimentally observed dose
      response relationships for a variety of cell types. This indicates that
      different, seemingly unrelated, low dose phenomena might be connected and driven
      by common core processes. With respect to the inter-cellular communication
      mechanism, we find that it can also account for the occurrence of radioadaptive
      responses, indicating redundancy in this respect. The model, however, also
      suggests that the communication mechanism can be vital for the long term survival
      of cell populations that are continuously exposed to relatively low levels of
      radiation, which cannot be achieved with the intracellular mechanism in our
      model. Experimental tests to address our model predictions are proposed. 

PMID- 24722168
TI  - Probiotic Lactobacillus rhamnosus GG enhanced Th1 cellular immunity but did not
      affect antibody responses in a human gut microbiota transplanted neonatal
      gnotobiotic pig model.
AB  - This study aims to establish a human gut microbiota (HGM) transplanted
      gnotobiotic (Gn) pig model of human rotavirus (HRV) infection and diarrhea, and
      to verify the dose-effects of probiotics on HRV vaccine-induced immune responses.
      Our previous studies using the Gn pig model found that probiotics dose
      dependently regulated both T cell and B cell immune responses induced by
      rotavirus vaccines. We generated the HGM transplanted neonatal Gn pigs through
      daily feeding of neonatal human fecal suspension to germ-free pigs for 3 days
      starting at 12 hours after birth. We found that attenuated HRV (AttHRV)
      vaccination conferred similar overall protection against rotavirus diarrhea and
      virus shedding in Gn pigs and HGM transplanted Gn pigs. HGM promoted the
      development of the neonatal immune system, as evidenced by the significantly
      enhanced IFN-gamma producing T cell responses and reduction of regulatory T cells
      and their cytokine production in the AttHRV-vaccinated pigs. The higher dose
      Lactobacillus rhamnosus GG (LGG) feeding (14 doses, up to 109 colony-forming-unit
      [CFU]/dose) effectively increased the LGG counts in the HGM Gn pig intestinal
      contents and significantly enhanced HRV-specific IFN-gamma producing T cell
      responses to the AttHRV vaccine. Lower dose LGG (9 doses, up to 106 CFU/dose) was
      ineffective. Neither doses of LGG significantly improved the protection rate, HRV
      specific IgA and IgG antibody titers in serum, or IgA antibody titers in
      intestinal contents compared to the AttHRV vaccine alone, suggesting that an even
      higher dose of LGG is needed to overcome the influence of the microbiota to
      achieve the immunostimulatory effect in the HGM pigs. This study demonstrated
      that HGM Gn pig is an applicable animal model for studying immune responses to
      rotavirus vaccines and can be used for studying interventions (i.e., probiotics
      and prebiotics) that may enhance the immunogenicity and protective efficacy of
      vaccines through improving the gut microbiota. 

PMID- 24722169
TI  - Linking differential radiation responses to glioma heterogeneity.
AB  - The phenotypic and genetic diversity that define tumor subpopulations within high
      grade glioma can lead to therapeutic resistance and tumor recurrence. Given that
      cranial irradiation is a frontline treatment for malignant glioma, understanding
      how irradiation selectively effects different cellular subpopulations within
      these heterogeneous cancers should help identify interventions targeted to better
      combat this deadly disease. To analyze the radiation response of distinct glioma
      subpopulations, 2 glioma cells lines (U251, A172) were cultured under conditions
      that promoted either adherence or non-adherent spheroids. Past work has
      demonstrated that subpopulations derived from defined culture conditions exhibit
      differences in karyotype, proliferation, gene expression and tumorigenicity.
      Spheroid cultures from each of the glioma cell lines were found to be more
      radiosensitive, which was consistent with higher levels of oxidative stress and
      lower levels of both oxidative phosphorylation and glycolytic metabolism 1 week
      following irradiation. In contrast, radioresistant non-spheroid parental cultures
      showed increased glycolytic activity in response to irradiation, while oxidative
      phosphorylation was affected to a lesser extent. Overall these data suggest that
      prolonged radiation-induced oxidative stress can compromise the metabolic state
      of certain glioma subpopulations thereby altering their sensitivity to an
      important therapeutic intervention used routinely for the control of glioma. 

PMID- 24722170
TI  - Genetic and environmental origins of hypospadias.
AB  - PURPOSE OF REVIEW: The purpose of this study was to review and comment on recent
      original presentations dealing with genetic and environmental factors in the
      cause of hypospadias. RECENT FINDINGS: The heritability is definitely high and
      having an affected family member is the highest identified risk factor so far.
      Many candidate genes and polymorphisms have been suggested for hypospadias. Some
      associations with hypospadias were found, and many of these were replicated
      inconsistently as would be expected in a complex disorder affected by both genes
      and environment. The consistent association of hypospadias with low birth weight,
      maternal hypertension, and preeclampsia suggests that placental insufficiency is
      a major risk factor. Maternal exposure to chemical pollutants or endocrine
      disruptors in high concentrations related to selected occupations or geographic
      areas may be additional risk factors for hypospadias, especially in genetically
      predisposed individuals. So far, however, no environmental chemical pollutants or
      endocrine disruptor with a general common impact on the risk for hypospadias in
      most societies has been demonstrated. SUMMARY: A major point that should be
      considered regarding the action of environmental toxicants in inducing
      hypospadias is the cumulative effects of multiple low-dose exposures.
      Furthermore, interactions between genetic and environmental factors may help to
      explain nonreplication in genetic studies of hypospadias.

PMID- 24722171
TI  - Testosterone and cardiovascular disease.
AB  - PURPOSE OF REVIEW: Use of testosterone among men is increasing rapidly. Low serum
      testosterone is positively associated with cardiovascular disease and its risk
      factors. No large randomized controlled trial (RCT) has assessed the effects of
      testosterone on cardiovascular outcomes. Here recent evidence accumulating from
      other sources - pharmacoepidemiology, Mendelian randomization studies and meta
      analysis of small RCTs - is reviewed to inform current testosterone usage. RECENT
      FINDINGS: In a large, well conducted pharmacoepidemiology study specifically
      testosterone prescription was associated with myocardial infarction. Two
      Mendelian randomization studies did not corroborate beneficial effects of higher
      endogenous testosterone on cardiovascular risk factors, but suggested higher
      endogenous testosterone raised LDL cholesterol and lowered HDL cholesterol. A
      comprehensive meta-analysis of RCTs summarizing 27 trials including 2994 men
      found increased risk of cardiovascular-related events on testosterone (odds ratio
      1.54, 95% confidence interval 1.09-2.18). SUMMARY: Contrary to expectations from
      observational studies, current indications suggest testosterone causes ischemic
      cardiovascular disease with corresponding implications for practice. A large RCT
      would undoubtedly settle the issue definitively. Given mounting evidence of harm
      and the urgency of the situation assembling all the evidence from completed RCTs
      of testosterone or androgen deprivation therapy and use of Mendelian
      randomization might generate a definitive answer most quickly.

PMID- 24722172
TI  - Cortisol metabolism in critical illness: implications for clinical care.
AB  - PURPOSE OF REVIEW: Critical illness is uniformly characterized by elevated plasma
      cortisol concentrations, traditionally attributed exclusively to increased
      cortisol production driven by an activated hypothalamic pituitary adrenal axis.
      However, as plasma adrenocorticotropic hormone (ACTH) concentrations are often
      not elevated or even low during critical illness, alternative mechanisms must
      contribute. RECENT FINDINGS: Recent investigations revealed that plasma clearance
      of cortisol is markedly reduced during critical illness, explained by suppressed
      expression and activity of the main cortisol metabolizing enzymes in liver and
      kidney. Furthermore, unlike previously inferred, cortisol production rate in
      critically ill patients was only moderately increased to less than double that of
      matched healthy subjects. In the face of low-plasma ACTH concentrations, these
      data suggest that other factors drive hypercortisolism during critical illness,
      which may suppress ACTH by feedback inhibition. These new insights add to the
      limitations of the current diagnostic tools to identify patients at risk of
      failing adrenal function during critical illness. They also urge to investigate
      the impact of lower hydrocortisone doses than those hitherto used. SUMMARY:
      Recent novel insights reshape the current understanding of the hormonal stress
      response to critical illness and further underline the need for more studies to
      unravel the pathophysiology of adrenal (dys)functioning during critical illness.

PMID- 24722174
TI  - Spontaneous breathing with biphasic positive airway pressure attenuates lung
      injury in hydrochloric acid-induced acute respiratory distress syndrome.
AB  - BACKGROUND: It has been proved that spontaneous breathing (SB) with biphasic
      positive airway pressure (BIPAP) can improve lung aeration in acute respiratory
      distress syndrome compared with controlled mechanical ventilation. The authors
      hypothesized that SB with BIPAP would attenuate lung injury in acute respiratory
      distress syndrome compared with pressure-controlled ventilation. METHODS: Twenty
      male New Zealand white rabbits with hydrochloric acid aspiration-induced acute
      respiratory distress syndrome were randomly ventilated using the BIPAP either
      with SB (BIPAP plus SB group) or without SB (BIPAP minus SB group) for 5 h.
      Inspiration pressure was adjusted to maintain the tidal volume at 6 ml/kg. Both
      groups received the same positive end-expiratory pressure level at 5 cm H2O for
      hemodynamic goals. Eight healthy animals without ventilatory support served as
      the control group. RESULTS: The BIPAP plus SB group presented a lower ratio of
      dead space ventilation to tidal volume, a lower respiratory rate, and lower
      minute ventilation. No significant difference in the protein levels of
      interleukin-6 and interleukin-8 in plasma, bronchoalveolar lavage fluid, and lung
      tissue were measured between the two experimental groups. However, SB resulted in
      lower messenger ribonucleic acid levels of interleukin-6 (mean +/- SD; 1.8 +/-
      0.7 vs. 2.6 +/- 0.5; P = 0.008) and interleukin-8 (2.2 +/- 0.5 vs. 2.9 +/- 0.6; P
      = 0.014) in lung tissues. In addition, lung histopathology revealed less injury
      in the BIPAP plus SB group (lung injury score, 13.8 +/- 4.6 vs. 21.8 +/- 5.7; P <
      0.05). CONCLUSION: In hydrochloric acid-induced acute respiratory distress
      syndrome, SB with BIPAP attenuated lung injury and improved respiratory function
      compared with controlled ventilation with low tidal volume.

PMID- 24722173
TI  - Testosterone, aging and survival: biomarker or deficiency.
AB  - PURPOSE OF REVIEW: The purpose of this study is to review recent studies that
      examined the association of endogenous and exogenous testosterone and mortality
      in older men. RECENT FINDINGS: Over the past several years, there has been a
      steep rise in testosterone prescriptions. The increased use of testosterone
      occurred in the context of several studies that reported an association between
      low serum testosterone and increased cardiovascular events and mortality. In
      contrast, recent studies have reported an association between testosterone
      treatment and adverse events. A testosterone treatment trial of mobility-impaired
      elderly men with prevalent cardiovascular disease was stopped due to increased
      cardiovascular events in the T-treated men and a meta-analysis reported increased
      cardiovascular events in T-treated men. In two recent large observational
      studies, testosterone treatment was associated with an increased risk for serious
      adverse cardiovascular events. SUMMARY: Low testosterone is associated with
      mortality in multiple cohort studies; however, it is unclear if this is a causal
      association or due to low testosterone being a biomarker of poor health. Given
      recent reports of adverse outcomes associated with testosterone treatment, a
      conservative use of testosterone is warranted in men with cardiovascular disease
      who may be at greater risk for adverse outcomes.

PMID- 24722175
TI  - Role of coagulation factor concentrates for reversing dabigatran-related
      anticoagulation.

PMID- 24722176
TI  - When to promote spontaneous respiratory activity in acute respiratory distress
      patients?

PMID- 24722177
TI  - The osteoblastogenesis potential of adipose mesenchymal stem cells in myeloma
      patients who had received intensive therapy.
AB  - Multiple myeloma (MM) is characterized by advanced osteolytic lesions resulting
      from the activation of osteoclasts (OCs) and inhibition of osteoblasts (OBs). OBs
      are derived from mesenchymal stem cells (MSCs) from the bone marrow (BM), however
      the pool and function of BMMSCs in MM patients (MM-BMMSCs) are reduced by myeloma
      cells (MCs) and cytokines secreted from MCs and related anti-MM treatment. Such
      reduction in MM-BMMSCs currently cannot be restored by any means. Recently,
      genetic aberrations of MM-BMMSCs have been noted, which further impaired their
      differentiation toward OBs. We hypothesize that the MSCs derived from adipose
      tissue (ADMSCs) can be used as alternative MSC sources to enhance the pool and
      function of OBs. Therefore, the purpose of this study was to compare the
      osteogenesis ability of paired ADMSCs and BMMSCs in MM patients who had completed
      intensive therapy. Fifteen MM patients who had received bortezomib-based
      induction and autologous transplantation were enrolled. At the third month after
      the transplant, the paired ADMSCs and BMMSCs were obtained and cultured. Compared
      with the BMMSCs, the ADMSCs exhibited a significantly higher expansion capacity
      (100% vs 13%, respectively; P = .001) and shorter doubling time (28 hours vs 115
      hours, respectively; P = .019). After inducing osteogenic differentiation,
      although the ALP activity did not differ between the ADMSCs and BMMSCs (0.78 U/ug
      vs 0.74+/-0.14 U/ug, respectively; P = .834), the ADMSCs still exhibited higher
      calcium mineralization, which was determined using Alizarin red S (1029 nmole vs
      341 nmole, respectively; P = .001) and von Kossa staining (2.6 E+05 um2 vs 5 E+04
      um2, respectively; P = .042), than the BMMSCs did. Our results suggested that
      ADMSCs are a feasible MSC source for enhancing the pool and function of OBs in MM
      patients who have received intensive therapy. 

PMID- 24722178
TI  - Interplay of the serine/threonine-kinase StkP and the paralogs DivIVA and GpsB in
      pneumococcal cell elongation and division.
AB  - Despite years of intensive research, much remains to be discovered to understand
      the regulatory networks coordinating bacterial cell growth and division. The
      mechanisms by which Streptococcus pneumoniae achieves its characteristic
      ellipsoid-cell shape remain largely unknown. In this study, we analyzed the
      interplay of the cell division paralogs DivIVA and GpsB with the ser/thr kinase
      StkP. We observed that the deletion of divIVA hindered cell elongation and
      resulted in cell shortening and rounding. By contrast, the absence of GpsB
      resulted in hampered cell division and triggered cell elongation. Remarkably,
      DeltagpsB elongated cells exhibited a helical FtsZ pattern instead of a Z-ring,
      accompanied by helical patterns for DivIVA and peptidoglycan synthesis.
      Strikingly, divIVA deletion suppressed the elongated phenotype of DeltagpsB
      cells. These data suggest that DivIVA promotes cell elongation and that GpsB
      counteracts it. Analysis of protein-protein interactions revealed that GpsB and
      DivIVA do not interact with FtsZ but with the cell division protein EzrA, which
      itself interacts with FtsZ. In addition, GpsB interacts directly with DivIVA.
      These results are consistent with DivIVA and GpsB acting as a molecular switch to
      orchestrate peripheral and septal PG synthesis and connecting them with the Z
      ring via EzrA. The cellular co-localization of the transpeptidases PBP2x and
      PBP2b as well as the lipid-flippases FtsW and RodA in DeltagpsB cells further
      suggest the existence of a single large PG assembly complex. Finally, we show
      that GpsB is required for septal localization and kinase activity of StkP, and
      therefore for StkP-dependent phosphorylation of DivIVA. Altogether, we propose
      that the StkP/DivIVA/GpsB triad finely tunes the two modes of peptidoglycan
      (peripheral and septal) synthesis responsible for the pneumococcal ellipsoid cell
      shape. 

PMID- 24722179
TI  - Prospective neoadjuvant analysis of PET imaging and mechanisms of resistance to
      Trastuzumab shows role of HIF1 and autophagy.
AB  - BACKGROUND: Although Trastuzumab has improved survival of HER2+ breast cancer
      patients, resistance to the agent pre-exists or develops through the course of
      therapy. Here we show that a specific metabolism and autophagy-related cancer
      cell phenotype relates to resistance of HER2+ breast cancer to Trastuzumab and
      chemotherapy. METHODS: Twenty-eight patients with locally advanced primary breast
      cancer were prospectively scheduled to received one cycle of Trastuzumab followed
      by a new biopsy on day 21, followed by taxol/Trastuzumab chemotherapy for four
      cycles before surgery. FDG PET/CT scan was used to monitor tumour response.
      Tissue samples were immunohistochemically analysed for metabolism and autophagy
      markers. RESULTS: In pre-Trastuzumab biopsies, the LC3A+/HER2+ cell population
      was correlated with HIF1alpha expression (P=0.01), while GLUT1 and LC3B
      expression were correlated with Ki67 proliferation index (P=0.01 and P=0.01,
      respectively). FDG PET tumour dimensions before therapy were correlated with LC3B
      expression (P=0.005). Administration of Trastuzumab significantly reduced
      clinical and PET-detected tumour dimensions (P<0.01). An inverse association of
      tumour response with the percentage of cells expressing HIF1alpha at baseline was
      documented (P=0.01). Administration of Trastuzumab resulted in a decrease of the
      proliferation index (P=0.004), GLUT1 (P=0.04) and HER2 (P=0.01) expression. In
      contrast, the percentage of LC3A+/HER2+ cells was increased (P=0.01). High
      baseline HIF1alpha expression was the only parameter associated with poorer
      pathological response to preoperative chemotherapy (P=0.001). CONCLUSIONS: As the
      HER2+/LC3A+ phenotype, which often overexpresses HIF1alpha, is a major
      subpopulation increasing after therapy with Trastuzumab, LC3A- and HIF1alpha
      targeting therapies should be investigated for the augmentation of anti-HER2
      therapy efficacy.

PMID- 24722180
TI  - Prognostic and predictive value of plasma testosterone levels in patients
      receiving first-line chemotherapy for metastatic castrate-resistant prostate
      cancer.
AB  - BACKGROUND: Biomarkers for metastatic castration-resistant prostatic cancer
      (mCRPC) are an unmet medical need. METHODS: The prognostic and predictive value
      for survival and response to salvage hormonal therapy (SHT) of baseline
      testosterone level (TL) was analysed in a cohort of 101 mCRPC patients
      participating in 9 non-hormonal first-line chemotherapy phase II-III trials.
      Inclusion criteria in all trials required a TL of <50 ng dl(-1). RESULTS: Median
      age: 70 years; visceral metastases: 19.8%; median prostate-specific antigen
      (PSA): 50.7 ng ml(-1); median TL: 11.5 ng dl(-1). Median overall survival (OS;
      24.5 months) was significantly longer if baseline TL was above (High TL; n=52)
      than under (Low TL; n=49) the TL median value (32.7 vs 22.4 months, respectively;
      P=0.0162, hazard ratio (HR)=0.6). The presence of anaemia was an unfavourable
      prognostic factor (median OS: 20.6 vs 28.4 months; P=0.0025, HR=1.88 (CI95%: 1.01
      3.48)). Patients presenting both anaemia and low testosterone had a worse outcome
      compared to those with one or none of them (median OS: 17.9 vs 22.4 vs 38.1
      months; P=0.0024). High vs Low TL was associated with PSA response rate (55.6% vs
      21.7%) in 41 patients receiving SHT. CONCLUSION: Testosterone level under
      castration range was a prognostic factor for survival mCRPC patients. The PSA
      response to SHT differed depending on TLs. Testosterone levels might help in
      treatment decision.

PMID- 24722181
TI  - Phase I/II trial of definitive carbon ion radiotherapy for prostate cancer:
      evaluation of shortening of treatment period to 3 weeks.
AB  - BACKGROUND: The purpose of this study was to evaluate the feasibility of a new
      shortened 3-week treatment schedule of carbon ion radiotherapy (CIRT) for
      prostate cancer. METHODS: Beginning in May 2010, patients with T1b-T3bN0M0,
      histologically proven prostate adenocarcinoma were enrolled in the phase II trial
      of CIRT. Patients received 51.6 GyE in 12 fractions over 3 weeks (protocol 1002).
      The primary end point was defined as the incidence of late adverse events that
      were evaluated based on the Common Terminology Criteria for Adverse Events
      version 4.0. Biochemical failure was determined using the Phoenix definition
      (nadir +2.0 ng ml(-1)). RESULTS: Forty-six patients were enrolled, and all
      patients were included in the analysis. The number of low-, intermediate-, and
      high-risk patients was 12 (26%), 9 (20%), and 25 (54%), respectively. The median
      follow-up period of surviving patients was 32.3 months. Two patients had
      intercurrent death without recurrence, and the remaining 44 patients were alive
      at the time of this analysis. In the analysis of late toxicities, grade 1 (G1)
      rectal haemorrhage was observed in 3 (7%) patients. The incidence of G1
      haematuria was observed in 6 (13%) patients, and G1 urinary frequency was
      observed in 17 (37%) patients. No ?G2 late toxicities were observed. In the
      analysis of acute toxicities, 2 (4%) patients showed G2 urinary frequency, and no
      other G2 acute toxicities were observed. CONCLUSIONS: The new shortened CIRT
      schedule over 3 weeks was considered as feasible. The analysis of long-term
      outcome is warranted.

PMID- 24722183
TI  - Identification of pathologically insignificant prostate cancer is not accurate in
      unscreened men.
AB  - BACKGROUND: Identification of men harbouring insignificant prostate cancer (PC)
      is important in selecting patients for active surveillance. Tools have been
      developed in PSA-screened populations to identify such men based on clinical and
      biopsy parameters. METHODS: Prospectively collected case series of 848 patients
      was treated with radical prostatectomy between July 2007 and October 2011 at an
      English tertiary care centre. Tumour volume was assessed by pathological
      examination. For each tool, receiver operator characteristics were calculated for
      predicting insignificant disease by three different criteria and the area under
      each curve compared. Comparison of accuracy in screened and unscreened
      populations was performed. RESULTS: Of 848 patients, 415 had Gleason 3+3 disease
      on biopsy. Of these, 32.0% had extra-prostatic extension and 50.2% were upgraded.
      One had positive lymph nodes. Two hundred and six (24% of cohort) were D'Amico
      low risk. Of these, 143 had more than two biopsy cores involved. None of the
      tools evaluated has adequate discriminative power in predicting insignificant
      tumour burden. Accuracy is low in PSA-screened and -unscreened populations.
      CONCLUSIONS: In our unscreened population, tools designed to identify
      insignificant PC are inaccurate. Detection of a wider size range of prostate
      tumours in the unscreened may contribute to relative inaccuracy.

PMID- 24722182
TI  - Molecular staging of lymph node-negative colon carcinomas by one-step nucleic
      acid amplification (OSNA) results in upstaging of a quarter of patients in a
      prospective, European, multicentre study.
AB  - BACKGROUND: Current histopathological staging procedures in colon carcinomas
      depend on midline division of the lymph nodes with one section of haematoxylin &
      eosin (H&E) staining only. By this method, tumour deposits outside this
      transection line may be missed and could lead to understaging of a high-risk
      group of stage UICC II cases, which recurs in ~20% of cases. A new diagnostic
      semiautomated system, one-step nucleic acid amplification (OSNA), detects
      cytokeratin (CK) 19 mRNA in lymph node metastases and enables the investigation
      of the whole lymph node. The objective of this study was to assess whether
      histopathological pN0 patients can be upstaged to stage UICC III by OSNA.
      METHODS: Lymph nodes from patients who were classified as lymph node negative
      after standard histopathology (single (H&E) slice) were subjected to OSNA. A
      result revealing a CK19 mRNA copy number >250, which makes sure to detect mainly
      macrometastases and not isolated tumour cells (ITC) or micrometastases only, was
      regarded as positive for lymph node metastases based on previous threshold
      investigations. RESULTS: In total, 1594 pN0 lymph nodes from 103 colon carcinomas
      (median number of lymph nodes per patient: 14, range: 1-46) were analysed with
      OSNA. Out of 103 pN0 patients, 26 had OSNA-positive lymph nodes, resulting in an
      upstaging rate of 25.2%. Among these were 6/37 (16.2%) stage UICC I and 20/66
      (30.3%) stage UICC II patients. Overall, 38 lymph nodes were OSNA positive: 19
      patients had one, 3 had two, 3 had three, and 1 patient had four OSNA-positive
      lymph nodes. CONCLUSIONS: OSNA resulted in an upstaging of over 25% of initially
      histopathologically lymph node-negative patients. OSNA is a standardised,
      observer-independent technique, allowing the analysis of the whole lymph node.
      Therefore, sampling bias due to missing investigation of certain lymph node
      tissue can be avoided, which may lead to a more accurate staging.

PMID- 24722184
TI  - Proteomics analysis of melanoma metastases: association between S100A13
      expression and chemotherapy resistance.
AB  - BACKGROUND: Disseminated cutaneous malignant melanoma (CMM) is commonly
      unresponsive to standard chemotherapies, and there are as yet no predictive
      markers of therapy response. METHODS: In the present study we collected fresh
      frozen pretreatment lymph-node metastasis samples (n=14) from melanoma patients
      with differential response to dacarbazine (DTIC) or temozolomide (TMZ)
      chemotherapy, to identify proteins with an impact on treatment response. We
      performed quantitative protein profiling using tandem mass spectrometry and
      compared the proteome differences between responders (R) and non-responders (NR),
      matched for age, gender and histopathological type of CMM. RESULTS: Biological
      pathway analyses showed several signalling pathways differing between R vs NR,
      including Rho signalling. Gene expression profiling data was available for a
      subset of the samples, and the results were compared with the proteomics data.
      Four proteins with differential expression between R and NR were selected for
      technical validation by immunoblotting (ISYNA1, F13A1, CSTB and S100A13), and
      CSTB and S100A13 were further validated on a larger sample set by
      immunohistochemistry (n=48). The calcium binding protein S100A13 was found to be
      significantly overexpressed in NR compared with R in all analyses performed.
      CONCLUSIONS: Our results suggest that S100A13 is involved in CMM resistance to
      DTIC/TMZ.

PMID- 24722185
TI  - Improved annotation of 3' untranslated regions and complex loci by combination of
      strand-specific direct RNA sequencing, RNA-Seq and ESTs.
AB  - The reference annotations made for a genome sequence provide the framework for
      all subsequent analyses of the genome. Correct and complete annotation in
      addition to the underlying genomic sequence is particularly important when
      interpreting the results of RNA-seq experiments where short sequence reads are
      mapped against the genome and assigned to genes according to the annotation.
      Inconsistencies in annotations between the reference and the experimental system
      can lead to incorrect interpretation of the effect on RNA expression of an
      experimental treatment or mutation in the system under study. Until recently, the
      genome-wide annotation of 3' untranslated regions received less attention than
      coding regions and the delineation of intron/exon boundaries. In this paper, data
      produced for samples in Human, Chicken and A. thaliana by the novel single
      molecule, strand-specific, Direct RNA Sequencing technology from Helicos
      Biosciences which locates 3' polyadenylation sites to within +/- 2 nt, were
      combined with archival EST and RNA-Seq data. Nine examples are illustrated where
      this combination of data allowed: (1) gene and 3' UTR re-annotation (including
      extension of one 3' UTR by 5.9 kb); (2) disentangling of gene expression in
      complex regions; (3) clearer interpretation of small RNA expression and (4)
      identification of novel genes. While the specific examples displayed here may
      become obsolete as genome sequences and their annotations are refined, the
      principles laid out in this paper will be of general use both to those annotating
      genomes and those seeking to interpret existing publically available annotations
      in the context of their own experimental data. 

PMID- 24722186
TI  - Emergence of motor circuit activity.
AB  - In the developing nervous system, ordered neuronal activity patterns can occur
      even in the absence of sensory input and to investigate how these arise, we have
      used the model system of the embryonic chicken spinal motor circuit, focusing on
      motor neurons of the lateral motor column (LMC). At the earliest stages of their
      molecular differentiation, we can detect differences between medial and lateral
      LMC neurons in terms of expression of neurotransmitter receptor subunits,
      including CHRNA5, CHRNA7, GRIN2A, GRIK1, HTR1A and HTR1B, as well as the KCC2
      transporter. Using patch-clamp recordings we also demonstrate that medial and
      lateral LMC motor neurons have subtly different activity patterns that reflect
      the differential expression of neurotransmitter receptor subunits. Using a
      combination of patch-clamp recordings in single neurons and calcium-imaging of
      motor neuron populations, we demonstrate that inhibition of nicotinic, muscarinic
      or GABA-ergic activity, has profound effects of motor circuit activity during the
      initial stages of neuromuscular junction formation. Finally, by analysing the
      activity of large populations of motor neurons at different developmental stages,
      we show that the asynchronous, disordered neuronal activity that occurs at early
      stages of circuit formation develops into organised, synchronous activity evident
      at the stage of LMC neuron muscle innervation. In light of the considerable
      diversity of neurotransmitter receptor expression, activity patterns in the LMC
      are surprisingly similar between neuronal types, however the emergence of
      patterned activity, in conjunction with the differential expression of
      transmitter systems likely leads to the development of near-mature patterns of
      locomotor activity by perinatal ages. 

PMID- 24722187
TI  - Tissue-specific methylation of human insulin gene and PCR assay for monitoring
      beta cell death.
AB  - The onset of metabolic dysregulation in type 1 diabetes (T1D) occurs after
      autoimmune destruction of the majority of pancreatic insulin-producing beta
      cells. We previously demonstrated that the DNA encoding the insulin gene is
      uniquely unmethylated in these cells and then developed a methylation-specific
      PCR (MSP) assay to identify circulating beta cell DNA in streptozotocin-treated
      mice prior to the rise in blood glucose. The current study extends to autoimmune
      non-obese diabetic (NOD) mice and humans, showing in NOD mice that beta cell
      death occurs six weeks before the rise in blood sugar and coincides with the
      onset of islet infiltration by immune cells, demonstrating the utility of MSP for
      monitoring T1D. We previously reported unique patterns of methylation of the
      human insulin gene, and now extend this to other human tissues. The methylation
      patterns of the human insulin promoter, intron 1, exon 2, and intron 2 were
      determined in several normal human tissues. Similar to our previous report, the
      human insulin promoter was unmethylated in beta cells, but methylated in all
      other tissues tested. In contrast, intron 1, exon 2 and intron 2 did not exhibit
      any tissue-specific DNA methylation pattern. Subsequently, a human MSP assay was
      developed based on the methylation pattern of the insulin promoter and human
      islet DNA was successfully detected in circulation of T1D patients after islet
      transplantation therapy. Signal levels of normal controls and pre-transplant
      samples were shown to be similar, but increased dramatically after islet
      transplantation. In plasma the signal declines with time but in whole blood
      remains elevated for at least two weeks, indicating that association of beta cell
      DNA with blood cells prolongs the signal. This assay provides an effective method
      to monitor beta cell destruction in early T1D and in islet transplantation
      therapy.

PMID- 24722189
TI  - Time course of physiological and psychological responses in humans during a 20
      day severe-cold-acclimation programme.
AB  - The time course of physiological and psychological markers during cold
      acclimation (CA) was explored. The experiment included 17 controlled (i.e., until
      the rectal temperature reached 35.5 degrees C or 170 min had elapsed; for the CA
      17 session, the subjects (n = 14) were immersed in water for the same amount of
      time as that used in the CA-1 session) head-out water immersions at a temperature
      of 14 degrees C over 20 days. The data obtained in this study suggest that the
      subjects exhibited a thermoregulatory shift from peripheral-to-central to solely
      central input thermoregulation, as well as from shivering to non-shivering
      thermogenesis throughout the CA. In the first six CA sessions, a hypothermic type
      of acclimation was found; further CA (CA-7 to CA-16) led to a transitional shift
      to a hypothermic-insulative type of acclimation. Interestingly, when the subjects
      were immersed in water for the same time as that used in the CA-1 session (CA
      17), the CA led to a hypothermic type of acclimation. The presence of a metabolic
      type of thermogenesis was evident only under thermoneutral conditions. Cold-water
      immersion decreased the concentration of cold-stress markers, reduced the
      activity of the innate immune system, suppressed specific immunity to a lesser
      degree and yielded less discomfort and cold sensation. We found a negative
      correlation between body mass index and Delta metabolic heat production before
      and after CA.

PMID- 24722191
TI  - Serum-stable quantum dot-protein hybrid nanocapsules for optical bio-imaging.
AB  - We introduce shell cross-linked protein/quantum dot (QD) hybrid nanocapsules as a
      serum-stable systemic delivery nanocarrier for tumor-targeted in vivo bio-imaging
      applications. Highly luminescent, heavy-metal-free Cu0.3InS2/ZnS (CIS/ZnS) core
      shell QDs are synthesized and mixed with amine-reactive six-armed poly(ethylene
      glycol) (PEG) in dichloromethane. Emulsification in an aqueous solution
      containing human serum albumin (HSA) results in shell cross-linked nanocapsules
      incorporating CIS/ZnS QDs, exhibiting high luminescence and excellent dispersion
      stability in a serum-containing medium. Folic acid is introduced as a tumor
      targeting ligand. The feasibility of tumor-targeted in vivo bio-imaging is
      demonstrated by measuring the fluorescence intensity of several major organs and
      tumor tissue after an intravenous tail vein injection of the nanocapsules into
      nude mice. The cytotoxicity of the QD-loaded HSA-PEG nanocapsules is also
      examined in several types of cells. Our results show that the cellular uptake of
      the QDs is critical for cytotoxicity. Moreover, a significantly lower level of
      cell death is observed in the CIS/ZnS QDs compared to nanocapsules loaded with
      cadmium-based QDs. This study suggests that the systemic tumor targeting of heavy
      metal-free QDs using shell cross-linked HSA-PEG hybrid nanocapsules is a
      promising route for in vivo tumor diagnosis with reduced non-specific toxicity. 

PMID- 24722190
TI  - Red blood cell distribution width and long-term outcome in patients undergoing
      percutaneous coronary intervention in the drug-eluting stenting era: a two-year
      cohort study.
AB  - BACKGROUND: Previous studies suggest the higher the red blood cell distribution
      width (RDW) the greater the risk of mortality in patients with coronary artery
      disease (CAD). However, the relationship between RDW and long-term outcome in CAD
      patients undergoing percutaneous coronary intervention (PCI) with a drug-eluting
      stent (DES) remains unclear. This study was designed to evaluate the long-term
      effect of RDW in patients treated with drug-eluting stent for CAD. METHODS: In
      total of 2169 non-anemic patients (1468 men, mean age 60.2 +/- 10.9 years) with
      CAD who had undergone successful PCI and had at least one drug-eluting stent were
      included in this study. Patients were grouped according to their baseline RDW:
      Quartile 1 (RDW<12.27%), Quartile 2 (12.27% <= RDW <13%), Quartile 3 (13% <=
      RDW<13.5%), and Quartile 4 (RDW >= 13.5). RESULTS: The incidence of in-hospital
      mortality and death or myocardial infarction was significantly higher in
      Quartiles 3 and 4 compared with Quartile 1 (P<0.05). After a follow-up of 29
      months, the incidence of all-cause death and stent thrombosis in Quartile 4 was
      higher than in Quartiles 1, 2, and 3 (P<0.05). The incidence of death/myocardial
      infarction/stroke and cardiac death in Quartile 4 was higher than in Quartiles 1
      and 2 (P<0.05). Multivariate Cox regression analysis showed that RDW was an
      independent predictor of all-cause death (hazard ratio (HR) = 1.37, 95%
      confidence interval (CI) = 1.15-1.62, P<0.001) and outcomes of death/myocardial
      infarction/stroke (HR = 1.21, 95% CI = 1.04-1.39, P = 0.013). The cumulative
      survival rate of Quartile 4 was lower than that of Quartiles 1, 2, and 3
      (P<0.05). CONCLUSION: High RDW is an independent predictor of long-term adverse
      clinical outcomes in non-anemic patients with CAD treated with DES.

PMID- 24722188
TI  - Protein interaction network of alternatively spliced isoforms from brain links
      genetic risk factors for autism.
AB  - Increased risk for autism spectrum disorders (ASD) is attributed to hundreds of
      genetic loci. The convergence of ASD variants have been investigated using
      various approaches, including protein interactions extracted from the published
      literature. However, these datasets are frequently incomplete, carry biases and
      are limited to interactions of a single splicing isoform, which may not be
      expressed in the disease-relevant tissue. Here we introduce a new interactome
      mapping approach by experimentally identifying interactions between brain
      expressed alternatively spliced variants of ASD risk factors. The Autism
      Spliceform Interaction Network reveals that almost half of the detected
      interactions and about 30% of the newly identified interacting partners represent
      contribution from splicing variants, emphasizing the importance of isoform
      networks. Isoform interactions greatly contribute to establishing direct physical
      connections between proteins from the de novo autism CNVs. Our findings
      demonstrate the critical role of spliceform networks for translating genetic
      knowledge into a better understanding of human diseases. 

PMID- 24722193
TI  - Phylogeographic analyses of submesophotic snappers Etelis coruscans and Etelis
      "marshi" (family Lutjanidae) reveal concordant genetic structure across the
      Hawaiian Archipelago.
AB  - The Hawaiian Archipelago has become a natural laboratory for understanding
      genetic connectivity in marine organisms as a result of the large number of
      population genetics studies that have been conducted across this island chain for
      a wide taxonomic range of organisms. However, population genetic studies have
      been conducted for only two species occurring in the mesophotic or submesophotic
      zones (30+m) in this archipelago. To gain a greater understanding of genetic
      connectivity in these deepwater habitats, we investigated the genetic structure
      of two submesophotic fish species (occurring ~200-360 m) in this archipelago. We
      surveyed 16 locations across the archipelago for submesophotic snappers Etelis
      coruscans (N = 787) and E. "marshi" (formerly E. carbunculus; N = 770) with 436
      490 bp of mtDNA cytochrome b and 10-11 microsatellite loci. Phylogeographic
      analyses reveal no geographic structuring of mtDNA lineages and recent
      coalescence times that are typical of shallow reef fauna. Population genetic
      analyses reveal no overall structure across most of the archipelago, a pattern
      also typical of dispersive shallow fishes. However some sites in the mid
      archipelago (Raita Bank to French Frigate Shoals) had significant population
      differentiation. This pattern of no structure between ends of the Hawaiian range,
      and significant structure in the middle, was previously observed in a
      submesophotic snapper (Pristipomoides filamentosus) and a submesophotic grouper
      (Hyporthodus quernus). Three of these four species also have elevated genetic
      diversity in the mid-archipelago. Biophysical larval dispersal models from
      previous studies indicate that this elevated diversity may result from larval
      supplement from Johnston Atoll, ~800 km southwest of Hawaii. In this case the
      boundaries of stocks for fishery management cannot be defined simply in terms of
      geography, and fishery management in Hawaii may need to incorporate external
      larval supply into management plans. 

PMID- 24722192
TI  - Epigenetic and genetic mechanisms in red cell biology.
AB  - PURPOSE OF REVIEW: Erythropoiesis, in which hematopoietic stem cells (HSCs)
      generate lineage-committed progenitors that mature into erythrocytes, is
      regulated by numerous chromatin modifying and remodeling proteins. We will focus
      on how epigenetic and genetic mechanisms mesh to establish the erythroid
      transcriptome and how studying erythropoiesis can yield genomic principles.
      RECENT FINDINGS: Trans-acting factor binding to small DNA motifs (cis-elements)
      underlies regulatory complex assembly at specific chromatin sites, and therefore
      unique transcriptomes. As cis-elements are often very small, thousands or
      millions of copies of a given element reside in a genome. Chromatin restricts
      factor access in a context-dependent manner, and cis-element-binding factors
      recruit chromatin regulators that mediate functional outputs. Technologies to map
      chromatin attributes of loci in vivo, to edit genomes and to sequence whole
      genomes have been transformative in discovering critical cis-elements linked to
      human disease. SUMMARY: Cis-elements mediate chromatin-targeting specificity, and
      chromatin regulators dictate cis-element accessibility/function, illustrating an
      amalgamation of genetic and epigenetic mechanisms. Cis-elements often function
      ectopically when studied outside of their endogenous loci, and complex strategies
      to identify nonredundant cis-elements require further development. Facile genome
      editing technologies provide a new approach to address this problem. Extending
      genetic analyses beyond exons and promoters will yield a rich pipeline of cis
      element alterations with importance for red cell biology and disease.

PMID- 24722194
TI  - A novel semiconductor compatible path for nano-graphene synthesis using CBr4
      precursor and Ga catalyst.
AB  - We propose a novel semiconductor compatible path for nano-graphene synthesis
      using precursors containing C-Br bonding and liquid catalyst. The unique
      combination of CBr4 as precursor and Ga as catalyst leads to efficient C
      precipitation at a synthesis temperature of 200  degrees C or lower. The non
      wetting nature of liquid Ga on tested substrates limits nano-scale graphene to
      form on Ga droplets and substrate surfaces at low synthesis temperatures of T <=
      450  degrees C and at droplet/substrate interfaces by C diffusion via droplet
      edges when T >= 400  degrees C. Good quality interface nano-graphene is
      demonstrated and the quality can be further improved by optimization of synthesis
      conditions and proper selection of substrate type and orientation. The proposed
      method provides a scalable and transfer-free route to synthesize
      graphene/semiconductor heterostructures, graphene quantum dots as well as
      patterned graphene nano-structures at a medium temperature range of 400-700 
      degrees C suitable for most important elementary and compound semiconductors.

PMID- 24722195
TI  - Optimal schedules of light exposure for rapidly correcting circadian
      misalignment.
AB  - Jet lag arises from a misalignment of circadian biological timing with the timing
      of human activity, and is caused by rapid transmeridian travel. Jet lag's
      symptoms, such as depressed cognitive alertness, also arise from work and social
      schedules misaligned with the timing of the circadian clock. Using experimentally
      validated mathematical models, we develop a new methodology to find
      mathematically optimal schedules of light exposure and avoidance for rapidly re
      entraining the human circadian system. In simulations, our schedules are found to
      significantly outperform other recently proposed schedules. Moreover, our
      schedules appear to be significantly more robust to both noise in light and to
      inter-individual variations in endogenous circadian period than other proposed
      schedules. By comparing the optimal schedules for thousands of different
      situations, and by using general mathematical arguments, we are also able to
      translate our findings into general principles of optimal circadian re
      entrainment. These principles include: 1) a class of schedules where circadian
      amplitude is only slightly perturbed, optimal for dim light and for small shifts
      2) another class of schedules where shifting occurs along the shortest path in
      phase-space, optimal for bright light and for large shifts 3) the determination
      that short light pulses are less effective than sustained light if the goal is to
      re-entrain quickly, and 4) the determination that length of daytime should be
      significantly shorter when delaying the clock than when advancing it. 

PMID- 24722196
TI  - Extracutaneous melanoma epidemiology in British Columbia.
AB  - The epidemiology of extracutaneous melanoma (ECM) is sparsely reported upon in
      the literature, and studies to date have been limited both by time and by
      geographic gaps in available data. Utilizing a comprehensive provincial cancer
      registry, we sought to analyze the incidence and survival rates of ECM on the
      basis of sex and anatomic distribution for the British Columbia, Canada
      population. Data on ECMs diagnosed between 1 January 1992 and 31 December 2006
      were obtained from the BC Cancer Registry. Anatomical sites of ECM were
      classified on the basis of ICD-9 codes, and incidence rates for each site were
      age standardized and grouped by sex. The 5-year survival rate for each anatomical
      grouping was tracked until 31 December 2011. A total of 922 primary ECMs were
      recorded in the BC Cancer Registry between 1992 and 2006, representing 5.1% of
      melanoma incidence. Ocular melanomas were most frequently reported, with an age
      standardized incidence rate (per million) of 10.6 for men and 8.5 for women. ECM
      patients were generally older at diagnosis and had poorer survival rates compared
      with cutaneous melanoma cases. Five-year survival rates for ECM varied markedly
      from 23.5% for genital lesions to 87.0% for ocular cases. Our ECM epidemiology
      results are largely consistent with previous studies from the USA and Europe.
      Where considerable differences in reported values do exist, the opportunity
      arises to assess the efficacy of melanoma detection, monitoring, and treatment
      strategies in different geographic regions. Our study represents the largest
      epidemiological investigation of ECM in Canada and provides a framework for
      future epidemiological comparisons. 

PMID- 24722197
TI  - Reduced magnetisation transfer ratio in cognitively impaired patients at the very
      early stage of multiple sclerosis: a prospective, multicenter, cross-sectional
      study.
AB  - OBJECTIVES: Cognitive impairment belongs to the core symptoms in multiple
      sclerosis (MS) and can already be present at the very early stages of the
      disease. The present study evaluated cognitive functioning after the first
      clinical presentation suggestive of MS and brain tissue damage in a non-lesion
      focused MRI approach by using magnetisation transfer imaging (MTI). SETTING AND
      PARTICIPANTS: 47 patients (15 men and 32 women; mean age: 31.17 years) after the
      first clinical event suggestive of MS were recruited in six different MS centres
      in Germany and underwent a neuropsychological test battery including tests for
      attention, memory and executive function as well as depression and fatigue. MTI
      and conventional MRI measures (T1/T2 lesion load) were assessed. In addition,
      Magnetisation Transfer Ratio (MTR) maps were calculated. Primary outcome measure
      was the investigation of cognitive dysfunction in very early MS in correlation to
      MRI data. RESULTS: 55.3% of patients with MS failed at least one test parameter.
      Specifically, 6% were reduced in working memory, 14.9% in focused attention,
      25.5% in figural learning and up to 14.9% in executive function. When the sample
      was subdivided into cognitively impaired and preserved, MTR scores within the
      cognitively impaired subgroup were significantly lower compared with the
      preserved group (t(43)=2.346, p=0.02*). No significant differences between the
      two groups were found in T2-weighted and T1-weighted lesion volume. CONCLUSIONS:
      After the first MS-related clinical event, 55.3% of patients showed distinct
      cognitive deficits. Cognitively impaired patients had significantly lower whole
      brain MTR, but no differences in focal brain lesion volumes supporting the idea
      that early cognitive deficits may be related to diffuse loss of brain tissue
      integrity.

PMID- 24722198
TI  - Preventing childhood obesity, phase II feasibility study focusing on South
      Asians: BEACHeS.
AB  - OBJECTIVE: To assess feasibility and acceptability of a multifaceted, culturally
      appropriate intervention for preventing obesity in South Asian children, and to
      obtain data to inform sample size for a definitive trial. DESIGN: Phase II
      feasibility study of a complex intervention. SETTING: 8 primary schools in inner
      city Birmingham, UK, within populations that are predominantly South Asian.
      PARTICIPANTS: 1090 children aged 6-8 years took part in the intervention. 571
      (85.9% from South Asian background) underwent baseline measures. 85.5% (n=488)
      were followed up 2 years later. INTERVENTIONS: The 1-year intervention consisted
      of school-based and family-based activities, targeting dietary and physical
      activity behaviours. The intervention was modified and refined throughout the
      period of delivery. MAIN OUTCOME MEASURES: Acceptability and feasibility of the
      intervention and of measurements required to assess outcomes in a definitive
      trial. The difference in body mass index (BMI) z-score between arms was used to
      inform sample size calculations for a definitive trial. RESULTS: Some
      intervention components (increasing school physical activity opportunities,
      family cooking skills workshops, signposting of local leisure facilities and
      attending day event at a football club) were feasible and acceptable. Other
      components were acceptable, but not feasible. Promoting walking groups was
      neither acceptable nor feasible. At follow-up, children in the intervention
      compared with the control group were less likely to be obese (OR 0.41; 0.19 to
      0.89), and had lower adjusted BMI z-score (-0.15 kg/m(2); 95% CI -0.27 to -0.03).
      CONCLUSIONS: The feasibility study informed components for an intervention
      programme. The favourable direction of outcome for weight status in the
      intervention group supports the need for a definitive trial. A cluster randomised
      controlled trial is now underway to assess the clinical and cost-effectiveness of
      the intervention. TRIAL REGISTRATION NUMBER: ISRCTN51016370.

PMID- 24722199
TI  - Shaky drawing: what is the rate of decline during prospective follow-up of
      essential tremor?
AB  - OBJECTIVE: Few studies have attempted to estimate the rate of decline over time
      in essential tremor (ET). The study objectives were to: (1) measure change,
      deriving a single summary measure for the entire group, and relate it to a
      commonly used clinical rating scale (ie, yearly change in points on that scale);
      (2) to assess change as a function of baseline clinical characteristics and (3)
      to answer the basic clinical question-is change perceptible/obvious during the
      follow-up of ET cases? SETTING: Prospective collection of longitudinal data on ET
      cases enrolled in a study of the environmental epidemiology of ET at Columbia
      University Medical Center (2000-2008). PARTICIPANTS: 116 unselected ET cases.
      INTERVENTIONS: Each case underwent the same evaluation at baseline and during one
      follow-up visit (mean follow-up interval (range)=5.8 (1.4-12.4) years). PRIMARY
      AND SECONDARY OUTCOME MEASURES: We assessed tremor during a commonly affected
      daily activity-drawing (ie, spirography), quantifying tremor using a simple,
      standardised 10-point rating scale developed by Bain and Findley. RESULTS: The
      Bain and Findley spiral score increased at an average rate of 0.12+/-0.23 points
      per year (maximum=1 point/year). In cases who had been followed for >=5 years,
      the change was obvious-a blinded neurologist was able to correctly order their
      spirals (baseline vs follow-up) in three-fourth of cases. The rate of change was
      higher in cases with versus without familial ET (p=0.01). CONCLUSIONS: Tremor in
      ET is slowly progressive; yet in the majority of cases, a clear difference in
      handwritten spirals was visible with a follow-up interval of five or more years.
      There may be differences between familial and non-familial ET in the rate of
      progression. These clinical data are intended to aid in the prognostic
      discussions that treating physicians have with their patients with ET.

PMID- 24722200
TI  - Intervention Now To Eliminate Repeat Unintended Pregnancy in Teenagers
      (INTERUPT): a systematic review of intervention effectiveness and cost
      effectiveness, qualitative and realist synthesis of implementation factors and
      user engagement.
AB  - BACKGROUND: The UK has the highest rate of teenage pregnancies in Western Europe,
      a fifth are repeat pregnancies. Unintended conceptions can result in emotional,
      psychological and educational harm to teenage girls, often with enduring
      implications for their life chances. Babies of teenage mothers have increased
      mortality in their first year and increased risk of poverty, educational
      underachievement and unemployment later in life, with associated societal costs.
      METHODS AND ANALYSIS: We will conduct a streamed, mixed-methods systematic review
      to find and evaluate interventions designed to reduce repeat unintended teen
      pregnancies. OUR AIMS ARE TO IDENTIFY:  Who is at greater risk of repeat
      unintended pregnancies? Which interventions are effective, cost-effective, how
      they work, in what setting and for whom? What are the barriers and facilitators
      to intervention uptake? Traditional electronic database searches will be
      augmented by targeted searches for evidence 'clusters' and guided by an advisory
      group of experts and stakeholders. To address the topic's inherent complexities,
      we will use a highly structured, innovative and iterative approach combining
      methodological techniques tailored to each stream of evidence. Quantitative data
      will be synthesised with reference to Cochrane guidelines for public health
      interventions. Qualitative evidence addressing facilitators and barriers to the
      uptake of interventions, experience and acceptability of interventions will be
      synthesised thematically. We will apply the principles of realist synthesis to
      uncover theories and mechanisms underpinning interventions. We will conduct an
      integration and overarching narrative of findings authenticated by client group
      feedback. ETHICS AND DISSEMINATION: We will publish the complete review in
      'Health Technology Assessment' and sections in specialist peer-reviewed journals.
      We will present at national and international conferences in the fields of public
      health, reproductive medicine and review methodology. Findings will be fed back
      to service users and practitioners via workshops run by the partner
      collaborators. TRAIL REGISTRATION NUMBER: PROSPERO CRD42012003168. COCHRANE
      REGISTRATION NUMBER: i=fertility/0068.

PMID- 24722201
TI  - The temporal dynamics of plasma fractalkine levels in ischemic stroke:
      association with clinical severity and outcome.
AB  - BACKGROUND: The chemokine fractalkine (CX3CL1, FKN) is involved in neural
      microglial interactions and is regarded as neuroprotective according to several
      in vivo studies of inflammatory and degenerative states of the brain. Recently,
      an association with outcome in human ischemic stroke has been proposed. In this
      study, we aimed to investigate the temporal pattern of FKN levels in acute
      ischemic stroke in relation to stroke severity and outcome. METHODS: FKN levels
      were measured in plasma specimens of fifty-five patients with acute ischemic
      stroke. Blood was available for time points 6 hours (h), 12 h, 3 days (d), 7 d
      and 90 d after stroke onset. Clinical outcome was evaluated using the modified
      Rankin Scale (mRS) at 7 d and 90 d. RESULTS: The time course of FKN significantly
      differs depending on stroke severity, with higher FKN levels linked to a lower
      severity. FKN levels in patients with moderate to severe strokes differ
      significantly from controls. In outcome analysis, we found an association of
      dynamics of FKN with clinical outcome. Decrease of FKN is pronounced in patients
      with worse outcome. Multivariate analysis including stroke severity and stroke
      etiology revealed that deltaFKN between 6 h and 3 d is independently associated
      with mRS at 90 d. In addition deltaFKN is inversely correlated with the extent of
      brain damage, as measured by S100B. CONCLUSIONS: FKN dynamics are independently
      associated with stroke outcome. Further studies might give insight on whether FKN
      is actively involved in the inflammatory cascade after acute ischemic stroke.

PMID- 24722202
TI  - Parasite fate and involvement of infected cells in the induction of CD4+ and CD8+
      T cell responses to Toxoplasma gondii.
AB  - During infection with the intracellular parasite Toxoplasma gondii, the
      presentation of parasite-derived antigens to CD4+ and CD8+ T cells is essential
      for long-term resistance to this pathogen. Fundamental questions remain regarding
      the roles of phagocytosis and active invasion in the events that lead to the
      processing and presentation of parasite antigens. To understand the most proximal
      events in this process, an attenuated non-replicating strain of T. gondii (the
      cpsII strain) was combined with a cytometry-based approach to distinguish active
      invasion from phagocytic uptake. In vivo studies revealed that T. gondii
      disproportionately infected dendritic cells and macrophages, and that infected
      dendritic cells and macrophages displayed an activated phenotype characterized by
      enhanced levels of CD86 compared to cells that had phagocytosed the parasite,
      thus suggesting a role for these cells in priming naive T cells. Indeed,
      dendritic cells were required for optimal CD4+ and CD8+ T cell responses, and the
      phagocytosis of heat-killed or invasion-blocked parasites was not sufficient to
      induce T cell responses. Rather, the selective transfer of cpsII-infected
      dendritic cells or macrophages (but not those that had phagocytosed the parasite)
      to naive mice potently induced CD4+ and CD8+ T cell responses, and conferred
      protection against challenge with virulent T. gondii. Collectively, these results
      point toward a critical role for actively infected host cells in initiating T.
      gondii-specific CD4+ and CD8+ T cell responses. 

PMID- 24722203
TI  - Prion protein facilitates synaptic vesicle release by enhancing release
      probability.
AB  - The cellular prion protein (PrP(C)) has been implicated in several
      neurodegenerative diseases as a result of protein misfolding. In humans, prion
      disease occurs typically with a sporadic origin where uncharacterized mechanisms
      induce spontaneous PrP(C) misfolding leading to neurotoxic PrP-scrapie formation
      (PrP(SC)). The consequences of misfolded PrP(C) signalling are well characterized
      but little is known about the physiological roles of PrP(C) and its involvement
      in disease. Here we investigated wild-type PrP(C) signalling in synaptic function
      as well as the effects of a disease-relevant mutation within PrP(C) (proline-to
      leucine mutation at codon 101). Expression of wild-type PrP(C) at the Drosophila
      neuromuscular junction leads to enhanced synaptic responses as detected in larger
      miniature synaptic currents which are caused by enlarged presynaptic vesicles.
      The expression of the mutated PrP(C) leads to reduction of both parameters
      compared with wild-type PrP(C). Wild-type PrP(C) enhances synaptic release
      probability and quantal content but reduces the size of the ready-releasable
      vesicle pool. Partially, these changes are not detectable following expression of
      the mutant PrP(C). A behavioural test revealed that expression of either protein
      caused an increase in locomotor activities consistent with enhanced synaptic
      release and stronger muscle contractions. Both proteins were sensitive to
      proteinase digestion. These data uncover new functions of wild-type PrP(C) at the
      synapse with a disease-relevant mutation in PrP(C) leading to diminished
      functional phenotypes. Thus, our data present essential new information possibly
      related to prion pathogenesis in which a functional synaptic role of PrP(C) is
      compromised due to its advanced conversion into PrP(SC) thereby creating a lack
      of-function scenario. 

PMID- 24722204
TI  - Competing targets of microRNA-608 affect anxiety and hypertension.
AB  - MicroRNAs (miRNAs) can repress multiple targets, but how a single de-balanced
      interaction affects others remained unclear. We found that changing a single
      miRNA-target interaction can simultaneously affect multiple other miRNA-target
      interactions and modify physiological phenotype. We show that miR-608 targets
      acetylcholinesterase (AChE) and demonstrate weakened miR-608 interaction with the
      rs17228616 AChE allele having a single-nucleotide polymorphism (SNP) in the 3'
      untranslated region (3'UTR). In cultured cells, this weakened interaction
      potentiated miR-608-mediated suppression of other targets, including CDC42 and
      interleukin-6 (IL6). Postmortem human cortices homozygote for the minor
      rs17228616 allele showed AChE elevation and CDC42/IL6 decreases compared with
      major allele homozygotes. Additionally, minor allele heterozygote and homozygote
      subjects showed reduced cortisol and elevated blood pressure, predicting risk of
      anxiety and hypertension. Parallel suppression of the conserved brain CDC42
      activity by intracerebroventricular ML141 injection caused acute anxiety in mice.
      We demonstrate that SNPs in miRNA-binding regions could cause expanded downstream
      effects changing important biological pathways. 

PMID- 24722205
TI  - A genome-wide association study on thyroid function and anti-thyroid peroxidase
      antibodies in Koreans.
AB  - Genetic factors are thought to be an important determinant of thyroid function
      and autoimmunity. However, there are limited data on genetic variants in Asians.
      In this study, we performed a genome-wide association study on plasma thyroid
      stimulating hormone (TSH) and free thyroxine (fT4) concentration and anti-thyroid
      peroxidase (anti-TPO) antibody positivity in 4238 Korean subjects. In the Stage 1
      genome scan, 3396 participants from the Ansung cohort were investigated using
      1.42 million genotyped or imputed markers. In the Stage 2 follow-up, 10 markers
      were genotyped in 842 participants from the Korean Longitudinal Study on Health
      and Aging cohort. An intronic variant in VAV3, rs12126655, which has been
      reported in Europeans, was significantly associated with plasma TSH concentration
      in the joint Stages 1 and 2 analyses (P = 2.2 * 10(-8)). We observed that a novel
      variant, rs2071403, located 75 bp proximal to the translational start site of TPO
      was significantly associated with plasma anti-TPO antibody positivity in the
      joint Stages 1 and 2 analyses (P = 1.3 * 10(-10)). This variant had a marginal
      sex-specific effect, and its association was more significant in females.
      Subjects possessing the rs2071403A allele, associated with an absence of the anti
      TPO antibody, had decreased TPO mRNA expression in their thyroid tissue. Another
      intronic variant of HLA-DPB2, rs733208, had a suggestive association with anti
      TPO antibody positivity (P = 4.2 * 10(-7)). In conclusion, we have identified
      genetic variants that are strongly associated with TSH level and anti-TPO
      antibody positivity in Koreans. Further replications and meta-analysis are
      required to confirm these findings. 

PMID- 24722206
TI  - Defining the therapeutic window in a severe animal model of spinal muscular
      atrophy.
AB  - Spinal muscular atrophy (SMA) is a neurodegenerative disease caused by the loss
      of a single gene, Survival Motor Neuron-1 (SMN1). Administration of a self
      complementary Adeno-Associated Virus vector expressing full-length SMN cDNA
      (scAAV-SMN) has proven an effective means to rescue the SMA phenotype in SMA
      mice, either by intravenous (IV) or intracerebroventricular (ICV) administration
      at very early time points. We have recently shown that ICV delivery of scAAV9-SMN
      is more effective than a similar dose of vector administered via an IV injection,
      thereby providing an important mechanism to examine a timeline for rescuing the
      disease and determining the therapeutic window in a severe model of SMA. In this
      report, we utilized a relatively severe mouse model of SMA, SMNDelta7. Animals
      were injected with scAAV9-SMN vector via ICV injection on a single day, from P2
      through P8. At each delivery point from P2 through P8, scAAV9-SMN decreased
      disease severity. A near complete rescue was obtained following P2 injection
      while a P8 injection produced a ~ 40% extension in survival. Analysis of the
      underlying neuromuscular junction (NMJ) pathology revealed that late-stage
      delivery of the vector failed to provide protection from NMJ defects despite
      robust SMN expression in the central nervous system. While our study demonstrates
      that a maximal benefit is obtained when treatment is delivered during pre
      symptomatic stages, significant therapeutic benefit can still be achieved after
      the onset of disease symptoms.

PMID- 24722207
TI  - Overexpression of LARGE suppresses muscle regeneration via down-regulation of
      insulin-like growth factor 1 and aggravates muscular dystrophy in mice.
AB  - Several types of muscular dystrophy are caused by defective linkage between alpha
      dystroglycan (alpha-DG) and laminin. Among these, dystroglycanopathy, including
      Fukuyama-type congenital muscular dystrophy (FCMD), results from abnormal
      glycosylation of alpha-DG. Recent studies have shown that like
      acetylglucosaminyltransferase (LARGE) strongly enhances the laminin-binding
      activity of alpha-DG. Therefore, restoration of the alpha-DG-laminin linkage by
      LARGE is considered one of the most promising possible therapies for muscular
      dystrophy. In this study, we generated transgenic mice that overexpress LARGE
      (LARGE Tg) and crossed them with dy(2J) mice and fukutin conditional knockout
      mice, a model for laminin alpha2-deficient congenital muscular dystrophy (MDC1A)
      and FCMD, respectively. Remarkably, in both the strains, the transgenic
      overexpression of LARGE resulted in an aggravation of muscular dystrophy. Using
      morphometric analyses, we found that the deterioration of muscle pathology was
      caused by suppression of muscle regeneration. Overexpression of LARGE in C2C12
      cells further demonstrated defects in myotube formation. Interestingly, a
      decreased expression of insulin-like growth factor 1 (IGF-1) was identified in
      both LARGE Tg mice and LARGE-overexpressing C2C12 myotubes. Supplementing the
      C2C12 cells with IGF-1 restored the defective myotube formation. Taken together,
      our findings indicate that the overexpression of LARGE aggravates muscular
      dystrophy by suppressing the muscle regeneration and this adverse effect is
      mediated via reduced expression of IGF-1. 

PMID- 24722208
TI  - different Roles for the axin interactions with the SAMP versus the second twenty
      amino acid repeat of adenomatous polyposis coli.
AB  - Wnt signalling is prevented by the proteosomal degradation of beta-catenin, which
      occurs in a destruction complex containing adenomatous polyposis coli (APC), APC
      like (APCL), Axin and Axin2. Truncating mutations of the APC gene result in the
      constitutive stabilisation of beta-catenin and the initiation of colon cancer,
      although tumour cells tolerate the expression of wild-type APCL. Using the
      colocalisation of overexpressed Axin, APC and APCL constructs as a readout of
      interaction, we found that Axin interacted with the second twenty amino acid
      repeat (20R2) of APC and APCL. This interaction involved a domain adjacent to the
      C-terminal DIX domain of Axin. We identified serine residues within the 20R2 of
      APCL that were involved in Axin colocalisation, the phosphorylation of truncated
      APCL and the down-regulation of beta-catenin. Our results indicated that Axin,
      but not Axin2, displaced APC, but not APCL, from the cytoskeleton and stimulated
      its incorporation into bright cytoplasmic dots that others have recognised as
      beta-catenin destruction complexes. The SAMP repeats in APC interact with the N
      terminal RGS domain of Axin. Our data showed that a short domain containing the
      first SAMP repeat in truncated APC was required to stimulate Axin
      oligomerisation. This was independent of Axin colocalisation with 20R2. Our data
      also suggested that the RGS domain exerted an internal inhibitory constraint on
      Axin oligomerisation. Considering our data and those from others, we discuss a
      working model whereby beta-catenin phosphorylation involves Axin and the 20R2 of
      APC or APCL and further processing of phospho-beta-catenin occurs upon the
      oligomerisation of Axin that is induced by binding the SAMP repeats in APC. 

PMID- 24722209
TI  - Tumor cell-activated CARD9 signaling contributes to metastasis-associated
      macrophage polarization.
AB  - Macrophages are critical immune effector cells of the tumor microenvironment that
      promote seeding, extravasation and persistent growth of tumor cells in primary
      tumors and metastatic sites. Tumor progression and metastasis are affected by
      dynamic changes in the specific phenotypes of macrophage subpopulations; however,
      the mechanisms by which tumor cells modulate macrophage polarization remain
      incompletely understood. Caspase recruitment domain-containing protein 9 (CARD9)
      is a central adaptor protein of innate immune responses to extracellular
      pathogens. We report that increased CARD9 expression is primarily localized in
      infiltrated macrophages and significantly associated with advanced
      histopathologic stage and the presence of metastasis. Using CARD9-deficient
      (CARD9(-/-)) mice, we show that bone marrow-derived CARD9 promotes liver
      metastasis of colon carcinoma cells. Mechanistic studies reveal that CARD9
      contributes to tumor metastasis by promoting metastasis-associated macrophage
      polarization through activation of the nuclear factor-kappa B signaling pathway.
      We further demonstrate that tumor cell-secreted vascular endothelial growth
      factor facilitates spleen tyrosine kinase activation in macrophages, which is
      necessary for formation of the CARD9-B-cell lymphoma/leukemia 10-mucosa
      associated lymphoid tissue lymphoma translocation protein 1 complex. Taken
      together, our results indicating that CARD9 is a regulator of metastasis
      associated macrophages will lead to new insights into evolution of the
      microenvironments supporting tumor metastasis, thereby providing targets for
      anticancer therapies. 

PMID- 24722210
TI  - Suppression of acetylpolyamine oxidase by selected AP-1 members regulates DNp73
      abundance: mechanistic insights for overcoming DNp73-mediated resistance to
      chemotherapeutic drugs.
AB  - Enhanced resistance to chemotherapy has been correlated with high levels of Delta
      Np73 (DNp73), an anti-apoptotic protein of the p53 tumor-suppressor family which
      inhibits the pro-apoptotic members such as p53 and TAp73. Although genotoxic
      drugs have been shown to induce DNp73 degradation, lack of mechanistic
      understanding of this process precludes strategies to enhance the targeting of
      DNp73 and improve treatment outcomes. Antizyme (Az) is a mediator of ubiquitin
      independent protein degradation regulated by the polyamine biosynthesis pathway.
      We show here that acetylpolyamine oxidase (PAOX), a catabolic enzyme of this
      pathway, upregulates DNp73 levels by suppressing its degradation via the Az
      pathway. Conversely, downregulation of PAOX activity by siRNA-mediated knockdown
      or chemical inhibition leads to DNp73 degradation in an Az-dependent manner. PAOX
      expression is suppressed by several genotoxic drugs, via selected members of the
      activator protein-1 (AP-1) transcription factors, namely c-Jun, JunB and FosB,
      which are required for stress-mediated DNp73 degradation. Finally, chemical- and
      siRNA-mediated inhibition of PAOX significantly reversed the resistant phenotype
      of DNp73-overexpressing cancer cells to genotoxic drugs. Together, these data
      define a critical mechanism for the regulation of DNp73 abundance, and reveal
      that inhibition of PAOX could widen the therapeutic index of cytotoxic drugs and
      overcome DNp73-mediated chemoresistance in tumors. 

PMID- 24722211
TI  - Fire raiser or fire accelerant? A meeting report on the 14th International TNF
      Conference 2013.

PMID- 24722212
TI  - Unexpected role of the steroid-deficiency protein ecdysoneless in pre-mRNA
      splicing.
AB  - The steroid hormone ecdysone coordinates insect growth and development, directing
      the major postembryonic transition of forms, metamorphosis. The steroid-deficient
      ecdysoneless1 (ecd1) strain of Drosophila melanogaster has long served to assess
      the impact of ecdysone on gene regulation, morphogenesis, or reproduction.
      However, ecd also exerts cell-autonomous effects independently of the hormone,
      and mammalian Ecd homologs have been implicated in cell cycle regulation and
      cancer. Why the Drosophila ecd1 mutants lack ecdysone has not been resolved.
      Here, we show that in Drosophila cells, Ecd directly interacts with core
      components of the U5 snRNP spliceosomal complex, including the conserved Prp8
      protein. In accord with a function in pre-mRNA splicing, Ecd and Prp8 are cell
      autonomously required for survival of proliferating cells within the larval
      imaginal discs. In the steroidogenic prothoracic gland, loss of Ecd or Prp8
      prevents splicing of a large intron from CYP307A2/spookier (spok) pre-mRNA, thus
      eliminating this essential ecdysone-biosynthetic enzyme and blocking the entry to
      metamorphosis. Human Ecd (hEcd) can substitute for its missing fly ortholog. When
      expressed in the Ecd-deficient prothoracic gland, hEcd re-establishes spok pre
      mRNA splicing and protein expression, restoring ecdysone synthesis and normal
      development. Our work identifies Ecd as a novel pre-mRNA splicing factor whose
      function has been conserved in its human counterpart. Whether the role of
      mammalian Ecd in cancer involves pre-mRNA splicing remains to be discovered. 

PMID- 24722213
TI  - Markers of epithelial to mesenchymal transition in association with survival in
      head and neck squamous cell carcinoma (HNSCC).
AB  - BACKGROUND: Elucidating the molecular phenotype of cancers with high metastatic
      potential will facilitate the development of novel therapeutic approaches to the
      disease. Gene expression profiles link epithelial to mesenchymal transition (EMT)
      phenotype with high-risk HNSCC. We sought to determine the role of protein
      biomarkers of EMT in head and neck squamous carcinoma (HNSC) prognosis. METHODS:
      Protein expression analysis of EGFR, beta-catenin and E-cadherin was performed on
      a cohort of 102 patients with HNSCC recruited between 1992 and 2005 using
      automated quantitative protein analysis (AQUA). We evaluated associations with
      clinicopathological parameters and prognosis. RESULTS: There were 67 patients
      with primary squamous cell carcinoma of the head and neck in this cohort who met
      inclusion criteria and for whom we had complete E-cadherin, beta-catenin and EGFR
      expression data. High E-cadherin expressers had longer 5-year progression-free
      survival (PFS) compared to those with low E-cadherin (59.7% versus 40.6%, p =
      0.04) and overall survival (OS) (69.6% versus 44.3%, p  = 0.05). Kaplan-Meier
      analysis showed that patients with low beta-catenin-expressing tumors trended
      toward worse 5-year PFS (p = 0.057). High EGFR expressers had inferior OS
      compared to low EGFR expressers (27.7% vs. 54%, p = 0.029). In the multivariable
      analysis context, E-cadherin remained an independent predictor of improved OS (HR
      = 0.204, 95% CI 0.043 to 0.972, p = 0.046) while EGFR trended towards
      significance for OS. CONCLUSIONS: The putative markers of EMT defined within a
      panel of HNSCC using AQUA are associated with tumors of poor prognosis.

PMID- 24722214
TI  - Prediction and experimental characterization of nsSNPs altering human PDZ-binding
      motifs.
AB  - Single nucleotide polymorphisms (SNPs) are a major contributor to genetic and
      phenotypic variation within populations. Non-synonymous SNPs (nsSNPs) modify the
      sequence of proteins and can affect their folding or binding properties.
      Experimental analysis of all nsSNPs is currently unfeasible and therefore
      computational predictions of the molecular effect of nsSNPs are helpful to guide
      experimental investigations. While some nsSNPs can be accurately characterized,
      for instance if they fall into strongly conserved or well annotated regions, the
      molecular consequences of many others are more challenging to predict. In
      particular, nsSNPs affecting less structured, and often less conserved regions,
      are difficult to characterize. Binding sites that mediate protein-protein or
      other protein interactions are an important class of functional sites on proteins
      and can be used to help interpret nsSNPs. Binding sites targeted by the PDZ
      modular peptide recognition domain have recently been characterized. Here we use
      this data to show that it is possible to computationally identify nsSNPs in PDZ
      binding motifs that modify or prevent binding to the proteins containing the
      motifs. We confirm these predictions by experimentally validating a selected
      subset with ELISA. Our work also highlights the importance of better
      characterizing linear motifs in proteins as many of these can be affected by
      genetic variations. 

PMID- 24722215
TI  - The Skin Cancer and Sun Knowledge (SCSK) Scale: Validity, Reliability, and
      Relationship to Sun-Related Behaviors Among Young Western Adults.
AB  - Increasing public knowledge remains one of the key aims of skin cancer awareness
      campaigns, yet diagnosis rates continue to rise. It is essential we measure skin
      cancer knowledge adequately so as to determine the nature of its relationship to
      sun-related behaviors. This study investigated the psychometric properties of a
      new measure of skin cancer knowledge, the Skin Cancer and Sun Knowledge (SCSK)
      scale. A total of 514 Western young adults (females n = 320, males n = 194) aged
      18 to 26 years completed measures of skin type, skin cancer knowledge, tanning
      behavior, sun exposure, and sun protection. Two-week test-retest of the SCSK was
      conducted with 52 participants. Internal reliability of the SCSK scale was
      acceptable (KR-20 = .69), test-retest reliability was high (r = .83, n = 52), and
      acceptable levels of face, content, and incremental validity were demonstrated.
      Skin cancer knowledge (as measured by SCSK) correlated with sun protection, sun
      exposure, and tanning behaviors in the female sample, but not in the males. Skin
      cancer knowledge appears to be more relevant to the behavior of young women than
      that of young males. We recommend that future research establish the validity of
      the SCSK across a range of participant groups.

PMID- 24722216
TI  - Barriers to mammography among inadequately screened women.
AB  - Mammography use has increased over the past 20 years, yet more than 30% of women
      remain inadequately screened. Structural barriers can deter individuals from
      screening, however, cognitive, emotional, and communication barriers may also
      prevent mammography use. This study sought to identify the impact of number and
      type of barriers on mammography screening status, and to examine whether number
      and type of barriers are different for never-screened and off-schedule women. A
      total of 182 women aged 40 years or older completed a computer kiosk facilitated
      survey as part of a larger patient navigator intervention. Logistic regression
      analysis indicated that breast cancer knowledge predicted whether a woman had
      ever had a mammogram (odds ratio [OR] = 1.04, 95% confidence interval [CI] = 1.02
      1.06, p = .0003), while the number of emotional, structural, and communication
      barriers predicted whether a woman was on-schedule for mammograms (OR = 0.79, 95%
      CI = 0.65-0.95, p = .0127). The results suggest that to increase the use of
      mammography at recommended regular intervals, interventions should be tailored
      toward current screening status. 

PMID- 24722217
TI  - Likelihood of Condom Use When Sexually Transmitted Diseases Are Suspected:
      Results From a Clinic Sample.
AB  - OBJECTIVE: To determine the event-level associations between perceived risk of
      sexually transmitted disease (STD) acquisition/transmission and condom use during
      penile-vaginal intercourse (PVI) among STD clinic attendees. METHOD: A
      convenience sample (N = 622) completed daily electronic assessments. Two
      questions were proxies of perceived risk: suspicion that the partner might
      currently have an STD and that "you" might currently have an STD. Participants
      reported whether condoms were used with PVI events in the past 24 hours.
      Generalized estimating equations determined the association between each of the
      perceived risk variables and event-level condom use. RESULTS: For the model
      pertaining to suspicion of sex partner infection, there were 16,674 events of
      PVI, with condom use during 10,552 of these events. The effect of current
      suspicion was significant after adjusting for gender and whether participants
      identified as African American/Black (estimated odds ratio = 2.17, 95% confidence
      interval = 1.57-3.00, P = .0001). The model pertaining to suspicion of self
      infection included 16,679 events of penile-vaginal sex, with condom use during
      10,557 of these events. Again, the effect of current suspicion was significant
      after adjusting for gender and African American/Black race (estimated odds ratio
      = 2.05, 95% confidence interval = 1.43-2.40, P = .0001). Tests for interactions
      with gender and with race were nonsignificant (all Ps > .25). CONCLUSION: Using
      an event-level research design, strong associations were found between
      perceptions of STD risk and condom use in a clinical population. Health care
      providers and other professionals may indirectly promote condom use by helping
      clinic patients realistically evaluate their risk of having sex with infected
      partners or of being a source of STD transmission to others.

PMID- 24722218
TI  - Positive Exercise Experience Facilitates Behavior Change via Self-Efficacy.
AB  - PURPOSE: Motivational processes can be set in motion when positive consequences
      of physical exercise are experienced. However, relationships between positive
      exercise experience and determinants of the motivational and the volitional
      phases of exercise change have attracted only sparse attention in research.
      METHOD: This research examines direct and indirect associations between positive
      experience and motivational as well as volitional self-efficacy, intention,
      action planning, and exercise in two distinct longitudinal samples. The first one
      originates from an online observational study in the general population with
      three measurement points in time (N = 350) and the second one from a clinical
      intervention study in a rehabilitation context with four measurement points (N =
      275). RESULTS: Structural equation modeling revealed the following: Positive
      experience is directly related with motivational self-efficacy as well as
      intentions in both samples. In the online sample only, positive experience is
      associated with volitional self-efficacy. In each sample, experience is
      indirectly associated with action planning via motivational self-efficacy and
      intentions. Moreover, action planning, in turn, predicts changes in physical
      exercise levels. CONCLUSIONS: Findings suggest a more prominent role of positive
      experience in the motivational than in the volitional phase of physical exercise
      change. Thus, this research contributes to the understanding of how positive
      experience is involved in the behavior change process.

PMID- 24722219
TI  - Community Impact of Pharmacy-Randomized Intervention to Improve Access to
      Syringes and Services for Injection Drug Users.
AB  - OBJECTIVES: In an effort to reduce HIV transmission among injection drug users
      (IDUs), New York State deregulated pharmacy syringe sales in 2001 through the
      Expanded Syringe Access Program by removing the requirement of a prescription.
      With evidence suggesting pharmacists' ability to expand their public health role,
      a structural, pharmacy-based intervention was implemented to determine whether
      expanding pharmacy practice to include provision of HIV risk reduction and
      social/medical services information during the syringe sale would (a) improve
      pharmacy staff attitudes toward IDUs (b) increase IDU syringe customers, and (c)
      increase prescription customer base in New York City neighborhoods with high
      burden of HIV and illegal drug activity. METHODS: Pharmacies (n = 88) were
      randomized into intervention (recruited IDU syringe customers into the study and
      delivered intervention activities), primary control (recruited IDU syringe
      customers only) and secondary control (did not recruit IDUs or deliver
      intervention activities) arms. RESULTS: Pharmacy staff in the intervention versus
      secondary control pharmacies showed significant decreases in the belief that
      selling syringes to IDUs causes community loitering. CONCLUSIONS: Structural
      interventions may be optimal approaches for changing normative attitudes about
      highly stigmatized populations.

PMID- 24722220
TI  - Tyrosine-mediated two-dimensional peptide assembly and its role as a bio-inspired
      catalytic scaffold.
AB  - In two-dimensional interfacial assemblies, there is an interplay between
      molecular ordering and interface geometry, which determines the final morphology
      and order of entire systems. Here we present the interfacial phenomenon of
      spontaneous facet formation in a water droplet driven by designed peptide
      assembly. The identified peptides can flatten the rounded top of a hemispherical
      droplet into a plane by forming a macroscopic two-dimensional crystal structure.
      Such ordering is driven by the folding geometry of the peptide, interactions of
      tyrosine and crosslinked stabilization by cysteine. We discover the key sequence
      motifs and folding structures and study their sequence-specific assembly. The
      well-ordered, densely packed, redox-active tyrosine units in the YYACAYY (H-Tyr
      Tyr-Ala-Cys-Ala-Tyr-Tyr-OH) film can trigger or enhance chemical/electrochemical
      reactions, and can potentially serve as a platform to fabricate a molecularly
      tunable, self-repairable, flat peptide or hybrid film. 

PMID- 24722221
TI  - Simple molecules as complex systems.
AB  - For individual molecules quantum mechanics (QM) offers a simple, natural and
      elegant way to build large-scale complex networks: quantized energy levels are
      the nodes, allowed transitions among the levels are the links, and transition
      intensities supply the weights. QM networks are intrinsic properties of molecules
      and they are characterized experimentally via spectroscopy; thus, realizations of
      QM networks are called spectroscopic networks (SN). As demonstrated for the
      rovibrational states of H2(16)O, the molecule governing the greenhouse effect on
      earth through hundreds of millions of its spectroscopic transitions (links), both
      the measured and first-principles computed one-photon absorption SNs containing
      experimentally accessible transitions appear to have heavy-tailed degree
      distributions. The proposed novel view of high-resolution spectroscopy and the
      observed degree distributions have important implications: appearance of a core
      of highly interconnected hubs among the nodes, a generally disassortative
      connection preference, considerable robustness and error tolerance, and an "ultra
      small-world" property. The network-theoretical view of spectroscopy offers a data
      reduction facility via a minimum-weight spanning tree approach, which can assist
      high-resolution spectroscopists to improve the efficiency of the assignment of
      their measured spectra. 

PMID- 24722223
TI  - Improving surgical ward care: development and psychometric properties of a global
      assessment toolkit.
AB  - OBJECTIVE: To develop a toolkit that covers the clinical, nontechnical, and
      empathic skills required for effective, safe surgical ward care. BACKGROUND:
      Despite the explosion of interest in patient safety, little attention has been
      placed on the skill set required for safe and effective surgical ward care.
      Currently, there is a lack of a systematic approach to improving ward care via
      assessing and improving residents' ward care skills. METHODS: A comprehensive
      evidence-based and expert-derived toolkit was developed, including a novel
      clinical checklist for ward care (Clinical Skills Assessment for Ward Care: C-SAW
      C); a novel team assessment scale for wards rounds (Teamwork Skills Assessment
      for Ward Care: T-SAW-C); and a revised version of a physician-patient interaction
      scale (Physician-Patient Interaction Global Rating Scale: PP-GIS). Interassessor
      reliability (kappa, intraclass correlation), internal consistency (Cronbach
      alpha), and convergent validity (Pearson r correlations) were evaluated
      statistically in 38 simulated scenarios (during which a patient rapidly
      deteriorated) involving 185 residents. RESULTS: Excellent interassessor
      reliability was obtained for C-SAW-C [median kappa = 0.89; median intraclass
      correlation coefficient (ICC) = 0.94], T-SAW-C (median ICC = 0.99), and the
      revised PP-GIs (kappa = 1.00; ICC = 0.98 or higher). Internal consistency was
      also very high for all team skills assessed by T-SAW-C (Cronbach alpha range 0.87
      0.94 across 6 skills) and the revised PP-GIS (Cronbach alpha = 0.96)-all P's <
      0.001. Significant positive correlations were obtained between the 3 assessments
      (r = 0.73-0.92, P < 0.001) thus showing evidence for convergent validity.
      CONCLUSIONS: We developed a toolkit that captures comprehensively the skills that
      are required for safe and effective ward care, including the high-risk situation
      where a patient decompensates. The toolkit offers a systematic evaluation of the
      quality and safety of surgical ward care and can be used to train and debrief
      residents' skills and performance.

PMID- 24722224
TI  - Quality of life in patients with esophageal squamous cell cancer receiving
      surgery or definitive chemoradiotherapy: results from a randomized controlled
      trial.

PMID- 24722222
TI  - Benchmarking outcomes in the critically injured burn patient.
AB  - OBJECTIVE: To determine and compare outcomes with accepted benchmarks in burn
      care at 6 academic burn centers. BACKGROUND: Since the 1960s, US morbidity and
      mortality rates have declined tremendously for burn patients, likely related to
      improvements in surgical and critical care treatment. We describe the baseline
      patient characteristics and well-defined outcomes for major burn injuries.
      METHODS: We followed 300 adults and 241 children from 2003 to 2009 through
      hospitalization, using standard operating procedures developed at study onset. We
      created an extensive database on patient and injury characteristics, anatomic and
      physiological derangement, clinical treatment, and outcomes. These data were
      compared with existing benchmarks in burn care. RESULTS: Study patients were
      critically injured, as demonstrated by mean % total body surface area (TBSA)
      (41.2 +/- 18.3 for adults and 57.8 +/- 18.2 for children) and presence of
      inhalation injury in 38% of the adults and 54.8% of the children. Mortality in
      adults was 14.1% for those younger than 55 years and 38.5% for those aged 55
      years and older. Mortality in patients younger than 17 years was 7.9%. Overall,
      the multiple organ failure rate was 27%. When controlling for age and % TBSA,
      presence of inhalation injury continues to be significant. CONCLUSIONS: This
      study provides the current benchmark for major burn patients. Mortality rates,
      notwithstanding significant % TBSA and presence of inhalation injury, have
      significantly declined compared with previous benchmarks. Modern day surgical and
      medically intensive management has markedly improved to the point where we can
      expect patients younger than 55 years with severe burn injuries and inhalation
      injury to survive these devastating conditions.

PMID- 24722225
TI  - Reply to letter: "Functional performance and quality of life in patients with
      squamous esophageal carcinoma receiving surgery or chemoradiation: results from a
      randomized trial".

PMID- 24722227
TI  - Enhancing genome-enabled prediction by bagging genomic BLUP.
AB  - We examined whether or not the predictive ability of genomic best linear unbiased
      prediction (GBLUP) could be improved via a resampling method used in machine
      learning: bootstrap aggregating sampling ("bagging"). In theory, bagging can be
      useful when the predictor has large variance or when the number of markers is
      much larger than sample size, preventing effective regularization. After
      presenting a brief review of GBLUP, bagging was adapted to the context of GBLUP,
      both at the level of the genetic signal and of marker effects. The performance of
      bagging was evaluated with four simulated case studies including known or unknown
      quantitative trait loci, and an application was made to real data on grain yield
      in wheat planted in four environments. A metric aimed to quantify candidate
      specific cross-validation uncertainty was proposed and assessed; as expected,
      model derived theoretical reliabilities bore no relationship with cross
      validation accuracy. It was found that bagging can ameliorate predictive
      performance of GBLUP and make it more robust against over-fitting. Seemingly, 25
      50 bootstrap samples was enough to attain reasonable predictions as well as
      stable measures of individual predictive mean squared errors. 

PMID- 24722228
TI  - High-resolution music with inaudible high-frequency components produces a lagged
      effect on human electroencephalographic activities.
AB  - High-quality digital sound sources with inaudible high-frequency components
      (above 20 kHz) have become available because of recent advances in information
      technology. Listening to such sounds has been shown to increase the alpha-band
      power of an electroencephalogram (EEG). The present study scrutinized the time
      course of this effect by recording EEG along with autonomic measures (skin
      conductance level and heart rate) and facial electromyograms (corrugator
      supercilii and zygomaticus major). Twenty university students (19-24 years old)
      listened to two types of a 200-s musical excerpt (J. S. Bach's French Suite No.
      5) with or without inaudible high-frequency components using a double-blind
      method. They were asked to rate the sound quality and to judge which excerpt
      contained high-frequency components. High-alpha EEG power (10.5-13 Hz) was larger
      for the excerpt with high-frequency components than for the excerpt without them.
      This effect was statistically significant only in the last quarter of the period
      (150-200 s). Participants were not able to distinguish between the excerpts,
      which did not produce any discernible differences in subjective, autonomic, and
      facial muscle measures. This study shows that inaudible high-frequency components
      have an impact on human brain activity without conscious awareness. Unlike a
      standard test for sound quality, at least 150 s of exposure is required to
      examine this effect in future research. 

PMID- 24722226
TI  - Fungal chitin dampens inflammation through IL-10 induction mediated by NOD2 and
      TLR9 activation.
AB  - Chitin is an essential structural polysaccharide of fungal pathogens and
      parasites, but its role in human immune responses remains largely unknown. It is
      the second most abundant polysaccharide in nature after cellulose and its
      derivatives today are widely used for medical and industrial purposes. We
      analysed the immunological properties of purified chitin particles derived from
      the opportunistic human fungal pathogen Candida albicans, which led to the
      selective secretion of the anti-inflammatory cytokine IL-10. We identified NOD2,
      TLR9 and the mannose receptor as essential fungal chitin-recognition receptors
      for the induction of this response. Chitin reduced LPS-induced inflammation in
      vivo and may therefore contribute to the resolution of the immune response once
      the pathogen has been defeated. Fungal chitin also induced eosinophilia in vivo,
      underpinning its ability to induce asthma. Polymorphisms in the identified chitin
      receptors, NOD2 and TLR9, predispose individuals to inflammatory conditions and
      dysregulated expression of chitinases and chitinase-like binding proteins, whose
      activity is essential to generate IL-10-inducing fungal chitin particles in
      vitro, have also been linked to inflammatory conditions and asthma. Chitin
      recognition is therefore critical for immune homeostasis and is likely to have a
      significant role in infectious and allergic disease.

PMID- 24722229
TI  - AltitudeOmics: Decreased reaction time after high altitude cognitive testing is a
      sensitive metric of hypoxic impairment.
AB  - Humans experiencing hypoxic conditions exhibit multiple signs of cognitive
      impairment, and high altitude expeditions may be undermined by abrupt degradation
      in mental performance. Therefore, the development of psychometric tools to
      quickly and accurately assess cognitive impairment is of great importance in
      aiding medical decision-making in the field, particularly in situations where
      symptoms may not be readily recognized. The present study used the Defense
      Automated Neurobehavioral Assessment (DANA), a ruggedized and portable
      neurocognitive assessment tool, to examine cognitive function in healthy human
      volunteers at sea level, immediately after ascending to an elevation over 5000 m,
      and following 16 days of acclimatization to this high altitude. The DANA battery
      begins with a simple reaction time test (SRT1) which is followed by a 20-min
      series of complex cognitive tests and ends with a second test of simple reaction
      time (SRT2). Tabulating the performance scores from these two tests allows the
      calculation of an SRT change score (dSRT=SRT1-SRT2) that reflects the potential
      effect of mental effort spent during the 20-min testing session. We found that
      dSRT, but not direct SRT in comparison to sea-level baseline performance, is
      highly sensitive to acute altitude-related performance deficits and the remission
      of impairment following successful acclimatization. Our results suggest that dSRT
      is a potentially useful analytical method to enhance the sensitivity of
      neurocognitive assessment.

PMID- 24722230
TI  - Order quantification of hexagonal periodic arrays fabricated by in situ solvent
      assisted nanoimprint lithography of block copolymers.
AB  - Directed self-assembly of block copolymer polystyrene-b-polyethylene oxide (PS-b
      PEO) thin film was achieved by a one-pot methodology of solvent vapor assisted
      nanoimprint lithography (SAIL). Simultaneous solvent-anneal and imprinting of a
      PS-b-PEO thin film on silicon without surface pre-treatments yielded a 250 nm
      line grating decorated with 20 nm diameter nanodots array over a large surface
      area of up to 4' wafer scale. The grazing-incidence small-angle x-ray scattering
      diffraction pattern showed the fidelity of the NIL stamp pattern replication and
      confirmed the periodicity of the BCP of 40 nm. The order of the hexagonally
      arranged nanodot lattice was quantified by SEM image analysis using the opposite
      partner method and compared to conventionally solvent-annealed block copolymer
      films. The imprint-based SAIL methodology thus demonstrated an improvement in
      ordering of the nanodot lattice of up to 50%, and allows significant time and
      cost reduction in the processing of these structures. 

PMID- 24722231
TI  - Exploring anagostic interactions in 5,15-porphodimethene metal complexes.
AB  - Using a metal templating strategy, 5,15-porphodimethene metal complexes were
      synthesized and their structure confirmed by single crystal X-ray analysis. The
      anagostic interaction causes distortion, while the hydrogen bonding interactions
      generate dimerisation and array formation in these complexes. 

PMID- 24722232
TI  - Pregeneral anaesthetic blood screening of dogs and cats attending a UK practice.

PMID- 24722233
TI  - Reference intervals for coagulation times using two point-of-care analysers in
      healthy pet rabbits (Oryctolagus cuniculus).
AB  - The purpose of this study was to establish reference intervals for prothrombin
      time (PT) and activated partial prothrombin time (aPTT) in healthy rabbits using
      two different point-of-care analysers (Idexx Coag DX and MS Quick Vet Coag
      Combo). These intervals would be useful in the diagnosis of coagulopathies and in
      the determination of coagulation status in critical patients. We are unaware of
      reports of coagulation values in pet rabbits. Blood samples were analysed from 81
      clinically healthy pet rabbits under three years of age (49 females and 32
      males). The reference intervals were as follows (non-parametric method for the MS
      Quick Vet Coag Combo and Box-Cox Robust method for the Idexx Coag DX, p<0.05
      limit for statistical significance): PT (MS Quick Vet Coag Combo)=N=33, 17.2
      28.5; PT (Idexx Coag DX)=N=48, 10.0-14.8, aPTT (MS Quick Vet Coag Combo)=N=33,
      103.2-159.2 and aPTT (Idexx Coag DX)=N=48, 104.2-159.1. PT was significantly
      longer using the MS Quick Vet Coag Combo. aPTT was significantly shorter with the
      MS Quick Vet Coag Combo. On each type of analyser, there was no significant
      difference between sexes and blood sampling sites. A significant difference was
      present for the use or not of anaesthesia with the MS Quick Vet Coag Combo
      analyser. This study on healthy pet rabbits will be useful in point-of-care
      diagnosis of coagulopathies. 

PMID- 24722234
TI  - Pet reptiles as potential reservoir of Campylobacter species with zoonotic
      potential.

PMID- 24722236
TI  - Three-dimensional printing of Hela cells for cervical tumor model in vitro.
AB  - Advances in three-dimensional (3D) printing have enabled the direct assembly of
      cells and extracellular matrix materials to form in vitro cellular models for 3D
      biology, the study of disease pathogenesis and new drug discovery. In this study,
      we report a method of 3D printing for Hela cells and gelatin/alginate/fibrinogen
      hydrogels to construct in vitro cervical tumor models. Cell proliferation, matrix
      metalloproteinase (MMP) protein expression and chemoresistance were measured in
      the printed 3D cervical tumor models and compared with conventional 2D planar
      culture models. Over 90% cell viability was observed using the defined printing
      process. Comparisons of 3D and 2D results revealed that Hela cells showed a
      higher proliferation rate in the printed 3D environment and tended to form
      cellular spheroids, but formed monolayer cell sheets in 2D culture. Hela cells in
      3D printed models also showed higher MMP protein expression and higher
      chemoresistance than those in 2D culture. These new biological characteristics
      from the printed 3D tumor models in vitro as well as the novel 3D cell printing
      technology may help the evolution of 3D cancer study. 

PMID- 24722235
TI  - Comparison of microbiological, histological, and immunomodulatory parameters in
      response to treatment with either combination therapy with prednisone and
      metronidazole or probiotic VSL#3 strains in dogs with idiopathic inflammatory
      bowel disease.
AB  - BACKGROUND: Idiopathic inflammatory bowel disease (IBD) is a common chronic
      enteropathy in dogs. There are no published studies regarding the use of
      probiotics in the treatment of canine IBD. The objectives were to compare
      responses to treatment with either combination therapy (prednisone and
      metronidazole) or probiotic strains (VSL#3) in dogs with IBD. METHODOLOGY AND
      PRINCIPAL FINDINGS: Twenty pet dogs with a diagnosis of IBD, ten healthy pet
      dogs, and archived control intestinal tissues from three euthanized dogs were
      used in this open label study. Dogs with IBD were randomized to receive either
      probiotic (D-VSL#3, n = 10) or combination drug therapy (D-CT, n = 10). Dogs were
      monitored for 60 days (during treatment) and re-evaluated 30 days after
      completing treatment. The CIBDAI (P<0.001), duodenal histology scores (P<0.001),
      and CD3+ cells decreased post-treatment in both treatment groups. FoxP3+ cells
      (p<0.002) increased in the D-VSL#3 group after treatment but not in the D-CT
      group. TGF-beta+ cells increased in both groups after treatment (P = 0.0043) with
      the magnitude of this increase being significantly greater for dogs in the D
      VSL#3 group compared to the D-CT group. Changes in apical junction complex
      molecules occludin and claudin-2 differed depending on treatment.
      Faecalibacterium and Turicibacter were significantly decreased in dogs with IBD
      at T0, with a significant increase in Faecalibacterium abundance observed in the
      animals treated with VSL#3 strains. CONCLUSIONS: A protective effect of VSL#3
      strains was observed in dogs with IBD, with a significant decrease in clinical
      and histological scores and a decrease in CD3+ T-cell infiltration. Protection
      was associated with an enhancement of regulatory T-cell markers (FoxP3+ and TGF
      beta+), specifically observed in the probiotic-treated group and not in animals
      receiving combination therapy. A normalization of dysbiosis after long-term
      therapy was observed in the probiotic group. Larger scale studies are warranted
      to evaluate the clinical efficacy of VSL#3 in canine IBD.

PMID- 24722237
TI  - Age-related incidence and family history in frontotemporal dementia: data from
      the Swedish Dementia Registry.
AB  - OBJECTIVES: Frontotemporal dementia (FTD) is considered to be a mainly early
      onset neurodegenerative disorder with a strong hereditary component. The aim of
      the study was to investigate age-related incidence and family history in FTD
      compared to other dementia disorders, especially Alzheimer's disease (AD).
      METHODS: The Swedish Dementia Registry (SveDem) registers all new cases of
      dementia diagnosed by the participating centres, including data on demographics,
      diagnosis, and investigations used. Data for the period 2008-2011 were extracted
      and compared with age-related population data on a regional and national level.
      RESULTS: There were 20 305 patients registered in SveDem during 2008-2011,
      whereof 352 received a diagnosis of FTD. Mean age at diagnosis for FTD was 69.6
      years and almost 70% of FTD cases were 65 years or older at the time of
      diagnosis. Both FTD and AD showed an increased incidence with age, which reached
      a maximum in the age group 80-84 years at 6.04 and 202 cases per 100 000 person
      years, respectively. The proportion of cases with a positive family history was
      significantly lower in FTD than in AD. CONCLUSIONS: Contrary to general opinion
      within the field, data from SveDem show that the incidence of FTD increases with
      age, and that the majority of cases are diagnosed after the age of 65 years. In
      addition, data from SveDem might suggest that the importance of hereditary
      factors in general is similar in FTD and AD. The recognition of these findings
      has important consequences for the diagnosis, treatment and care of patients with
      FTD.

PMID- 24722238
TI  - Opposing functions of Akt isoforms in lung tumor initiation and progression.
AB  - BACKGROUND: The phosphatidylinositol 3-kinase-regulated protein kinase, Akt,
      plays an important role in the initiation and progression of human cancer.
      Mammalian cells express three Akt isoforms (Akt1-3), which are encoded by
      distinct genes. Despite sharing a high degree of amino acid identity, phenotypes
      observed in knockout mice suggest that Akt isoforms are not functionally
      redundant. The relative contributions of the different Akt isoforms to
      oncogenesis, and the effect of their deficiencies on tumor development, are not
      well understood. METHODS: Here we demonstrate that Akt isoforms have non
      overlapping and sometimes opposing functions in tumor initiation and progression
      using a viral oncogene-induced mouse model of lung cancer and Akt isoform
      specific knockout mice. RESULTS: Akt1 ablation significantly delays initiation of
      lung tumor growth, whereas Akt2 deficiency dramatically accelerates tumorigenesis
      in this mouse model. Ablation of Akt3 had a small, not statistically significant,
      stimulatory effect on tumor induction and growth by the viral oncogene. Terminal
      deoxynucleotidyl transferase-mediated dUTP nick end labeling and Ki67
      immunostaining of lung tissue sections revealed that the delayed tumor induction
      in Akt1-/- mice was due to the inhibitory effects of Akt1 ablation on cell growth
      and survival. Conversely, the accelerated growth rate of lung tumors in Akt2-/-
      and Akt3-/- mice was due to increased cell proliferation and reduced tumor cell
      apoptosis. Investigation of Akt signaling in tumors from Akt knockout mice
      revealed that the lack of Akt1 interrupted the propagation of signaling in tumors
      to the critical downstream targets, GSK-3alpha/beta and mTOR. CONCLUSIONS: These
      results demonstrate that the degree of functional redundancy between Akt isoforms
      in the context of lung tumor initiation is minimal. Given that this mouse model
      exhibits considerable similarities to human lung cancer, these findings have
      important implications for the design and use of Akt inhibitors for the treatment
      of lung cancer.

PMID- 24722240
TI  - Cationic antimicrobial peptides as potential new therapeutic agents in neonates
      and children: a review.
AB  - PURPOSE OF REVIEW: Antimicrobial resistance towards conventional antibiotics is a
      serious problem for modern medicine and for our society. Multidrug-resistant
      bacteria are very difficult to treat and treatment options have begun to run out.
      Here, we summarize the newest studies of drug development using cationic
      antimicrobial peptides as lead molecules for novel antimicrobial drugs. RECENT
      FINDINGS: A new development is the use of antimicrobial peptides not only as
      direct antimicrobial lead structures but also using their ability to influence
      the immune system. Such approaches can be used to develop drugs that influence
      the immune system in a unique way, supporting specific branches of immune cells
      in order to clear infection. Applying such an 'immune boost' would also minimize
      the danger of new resistance emerging in bacteria. In addition, searching for and
      testing substances that trigger the production of host antimicrobial peptides is
      still ongoing and opens up a totally new avenue for the use of antimicrobial
      peptides against infections. Currently, more than 10 clinical trials, phase 2 or
      3, using antimicrobial peptides are in progress or have been recently completed.
      SUMMARY: Multidrug resistance is an urgent problem for modern medicine and novel
      antimicrobials are needed. Despite some drawbacks, antimicrobial peptides seem
      now to appear more numerous in clinical trials, indicating the success in
      developing peptides into novel therapeutics. This can be critical especially for
      neonates and children, as treatment options for infections with Gram-negatives in
      neonatal ICUs are becoming rare.

PMID- 24722239
TI  - Biophysical properties of intrinsically disordered p130Cas substrate domain-
      implication in mechanosensing.
AB  - Mechanical stretch-induced tyrosine phosphorylation in the proline-rich 306
      residue substrate domain (CasSD) of p130Cas (or BCAR1) has eluded an
      experimentally validated structural understanding. Cellular p130Cas tyrosine
      phosphorylation is shown to function in areas without internal actomyosin
      contractility, sensing force at the leading edge of cell migration. Circular
      dichroism shows CasSD is intrinsically disordered with dominant polyproline type
      II conformations. Strongly conserved in placental mammals, the proline-rich
      sequence exhibits a pseudo-repeat unit with variation hotspots 2-9 residues
      before substrate tyrosine residues. Atomic-force microscopy pulling experiments
      show CasSD requires minimal extension force and exhibits infrequent, random
      regions of weak stability. Proteolysis, light scattering and ultracentrifugation
      results show that a monomeric intrinsically disordered form persists for CasSD in
      solution with an expanded hydrodynamic radius. All-atom 3D conformer sampling
      with the TraDES package yields ensembles in agreement with experiment when coil
      biased sampling is used, matching the experimental radius of gyration. Increasing
      beta-sampling propensities increases the number of prolate conformers. Combining
      the results, we conclude that CasSD has no stable compact structure and is
      unlikely to efficiently autoinhibit phosphorylation. Taking into consideration
      the structural propensity of CasSD and the fact that it is known to bind to LIM
      domains, we propose a model of how CasSD and LIM domain family of transcription
      factor proteins may function together to regulate phosphorylation of CasSD and
      effect machanosensing. 

PMID- 24722241
TI  - Concentrations of human chorionic gonadotrophin in very early pregnancy and
      subsequent pre-eclampsia: a cohort study.
AB  - STUDY QUESTION: Are low serum concentrations of human chorionic gonadotrophin
      (hCG) in very early pregnancy associated with pre-eclampsia risk? SUMMARY ANSWER:
      Low hCG concentrations in very early pregnancy are associated with increased risk
      of severe pre-eclampsia. WHAT IS KNOWN ALREADY: Low maternal serum concentrations
      of hCG early in pregnancy may indicate impaired proliferation or invasion of
      trophoblast cells, and thus low hCG concentrations may serve as a marker for
      impaired placental development. Impaired placental development is assumed to be a
      cause of pre-eclampsia, but there is little prospective evidence to support this
      hypothesis. STUDY DESIGN, SIZE, DURATION: We performed a prospective cohort study
      of pregnancies after IVF at Oslo University Hospital 1996-2010 with linkage to
      the Medical Birth Registry of Norway to obtain information on pre-eclampsia
      development. PARTICIPANTS/MATERIALS, SETTING, METHODS: We included 2405
      consecutive singleton pregnancies and examined the association of maternal serum
      hCG concentrations (measured using Elecsys, Roche) on Day 12 after embryo
      transfer with the risk of any pre-eclampsia and of mild and severe pre-eclampsia.
      MAIN RESULTS AND THE ROLE OF CHANCE: HCG concentrations were inversely associated
      with pre-eclampsia risk in a dose-dependent manner (Ptrend 0.02). Compared with
      women with hCG >=150 IU/l, women with hCG <50 IU/l were at 2-fold higher overall
      risk of pre-eclampsia [absolute risk 6.4 versus 2.8%; odds ratio (OR) 2.3, 95%
      confidence interval (CI) 1.2-4.7]. The inverse association was restricted to
      severe pre-eclampsia (Ptrend 0.01), thus, women with hCG <50 IU/l were at 4-fold
      higher risk of severe pre-eclampsia than women with hCG >=150 IU/l (absolute risk
      3.6 versus 0.9%; OR 4.2, 95% CI 1.4-12.2). For mild pre-eclampsia, there was no
      corresponding association (Ptrend 0.36). LIMITATIONS, REASONS FOR CAUTION:
      Results for IVF pregnancies may not be generalizable to spontaneously conceived
      pregnancies. WIDER IMPLICATIONS OF THE FINDINGS: Plausible causes of low maternal
      hCG concentrations very early in pregnancy include impaired placental development
      and delayed implantation. Thus, these results provide prospective evidence to
      support the hypothesis that impaired placental development may be associated with
      subsequent development of severe pre-eclampsia. STUDY FUNDING/COMPETING INTEREST:
      The study was financially supported by the Research Council of Norway. None of
      the authors has any conflict of interest to declare.

PMID- 24722242
TI  - Angiopoietin 2 induces pericyte apoptosis via alpha3beta1 integrin signaling in
      diabetic retinopathy.
AB  - Pericyte loss is an early characteristic change in diabetic retinopathy (DR).
      Despite accumulating evidence that hyperglycemia-induced angiopoietin 2 (Ang2)
      has a central role in pericyte loss, the precise molecular mechanism has not been
      elucidated. This study investigated the role of Ang2 in pericyte loss in DR. We
      demonstrated that pericyte loss occurred with Ang2 increase in the diabetic mouse
      retina and that the source of Ang2 could be the endothelial cell. Ang2 induced
      pericyte apoptosis via the p53 pathway under high glucose, whereas Ang2 alone did
      not induce apoptosis. Integrin, not Tie-2 receptor, was involved for Ang2-induced
      pericyte apoptosis under high glucose as an Ang2 receptor. High glucose changed
      the integrin expression pattern, which increased integrin alpha3 and beta1 in the
      pericyte. Furthermore, Ang2-induced pericyte apoptosis in vitro was effectively
      attenuated via p53 suppression by blocking integrin alpha3 and beta1. Although
      intravitreal injection of Ang2 induced pericyte loss in C57BL/6J mice retina in
      vivo, intravitreal injection of anti-integrin alpha3 and beta1 antibodies
      attenuated Ang2-induced pericyte loss. Taken together, Ang2 induced pericyte
      apoptosis under high glucose via alpha3beta1 integrin. Glycemic control or
      blocking Ang2/integrin signaling could be a potential therapeutic target to
      prevent pericyte loss in early DR.

PMID- 24722243
TI  - Parp inhibition prevents ten-eleven translocase enzyme activation and
      hyperglycemia-induced DNA demethylation.
AB  - Studies from human cells, rats, and zebrafish have documented that hyperglycemia
      (HG) induces the demethylation of specific cytosines throughout the genome. We
      previously documented that a subset of these changes become permanent and may
      provide, in part, a mechanism for the persistence of complications referred to as
      the metabolic memory phenomenon. In this report, we present studies aimed at
      elucidating the molecular machinery that is responsible for the HG-induced DNA
      demethylation observed. To this end, RNA expression and enzymatic activity assays
      indicate that the ten-eleven translocation (Tet) family of enzymes are activated
      by HG. Furthermore, through the detection of intermediates generated via
      conversion of 5-methyl-cytosine back to the unmethylated form, the data were
      consistent with the use of the Tet-dependent iterative oxidation pathway. In
      addition, evidence is provided that the activity of the poly(ADP-ribose)
      polymerase (Parp) enzyme is required for activation of Tet activity because the
      use of a Parp inhibitor prevented demethylation of specific loci and the
      accumulation of Tet-induced intermediates. Remarkably, this inhibition was
      accompanied by a complete restoration of the tissue regeneration deficit that is
      also induced by HG. The ultimate goal of this work is to provide potential new
      avenues for therapeutic discovery.

PMID- 24722244
TI  - Metabolic crosstalk: molecular links between glycogen and lipid metabolism in
      obesity.
AB  - Glycogen and lipids are major storage forms of energy that are tightly regulated
      by hormones and metabolic signals. We demonstrate that feeding mice a high-fat
      diet (HFD) increases hepatic glycogen due to increased expression of the
      glycogenic scaffolding protein PTG/R5. PTG promoter activity was increased and
      glycogen levels were augmented in mice and cells after activation of the
      mechanistic target of rapamycin complex 1 (mTORC1) and its downstream target
      SREBP1. Deletion of the PTG gene in mice prevented HFD-induced hepatic glycogen
      accumulation. Of note, PTG deletion also blocked hepatic steatosis in HFD-fed
      mice and reduced the expression of numerous lipogenic genes. Additionally, PTG
      deletion reduced fasting glucose and insulin levels in obese mice while improving
      insulin sensitivity, a result of reduced hepatic glucose output. This metabolic
      crosstalk was due to decreased mTORC1 and SREBP activity in PTG knockout mice or
      knockdown cells, suggesting a positive feedback loop in which once accumulated,
      glycogen stimulates the mTORC1/SREBP1 pathway to shift energy storage to
      lipogenesis. Together, these data reveal a previously unappreciated broad role
      for glycogen in the control of energy homeostasis.

PMID- 24722245
TI  - Mitogen-activated protein kinase phosphatase 3 (MKP-3)-deficient mice are
      resistant to diet-induced obesity.
AB  - Mitogen-activated protein kinase phosphatase 3 (MKP-3) is a negative regulator of
      extracellular signal-related kinase signaling. Our laboratory recently
      demonstrated that MKP-3 plays an important role in obesity-related hyperglycemia
      by promoting hepatic glucose output. This study shows that MKP-3 deficiency
      attenuates body weight gain induced by a high-fat diet (HFD) and protects mice
      from developing obesity-related hepatosteatosis. Triglyceride (TG) contents are
      dramatically decreased in the liver of MKP-3(-/-) mice fed an HFD compared with
      wild-type (WT) controls. The absence of MKP-3 also reduces adiposity, possibly by
      repressing adipocyte differentiation. In addition, MKP-3(-/-) mice display
      increased energy expenditure, enhanced peripheral glucose disposal, and improved
      systemic insulin sensitivity. We performed global phosphoproteomic studies to
      search for downstream mediators of MKP-3 action in liver lipid metabolism. Our
      results revealed that MKP-3 deficiency increases the phosphorylation of histone
      deacetylase (HDAC) 1 on serine 393 by 3.3-fold and HDAC2 on serine 394 by 2.33
      fold. Activities of HDAC1 and 2 are increased in the livers of MKP-3(-/-) mice
      fed an HFD. Reduction of HDAC1/2 activities is sufficient to restore TG content
      of MKP-3(-/-) primary hepatocytes to a level similar to that in WT cells.

PMID- 24722247
TI  - Retraction. Activation of aldose reductase by interaction with tubulin and
      involvement of this mechanism in diabetic cataract formation. Diabetes. 10 April
      2014 [Epub ahead of print]. DOI: 10.2337/db13-1265.

PMID- 24722246
TI  - I prostanoid receptor-mediated inflammatory pathway promotes hepatic
      gluconeogenesis through activation of PKA and inhibition of AKT.
AB  - Nonsteroidal anti-inflammatory drugs (NSAIDs), including acetylsalicylic acid
      (ASA), improve glucose metabolism in diabetic subjects, although the underlying
      mechanisms remain unclear. In this study, we observed dysregulated expression of
      cyclooxygenase-2, prostacyclin biosynthesis, and the I prostanoid receptor (IP)
      in the liver's response to diabetic stresses. High doses of ASA reduced hepatic
      prostaglandin generation and suppressed hepatic gluconeogenesis in mice during
      fasting, and the hypoglycemic effect of ASA could be restored by IP agonist
      treatment. IP deficiency inhibited starvation-induced hepatic gluconeogenesis,
      thus inhibiting the progression of diabetes, whereas hepatic overexpression of IP
      increased gluconeogenesis. IP deletion depressed cAMP-dependent CREB
      phosphorylation and elevated AKT phosphorylation by suppressing PI3K-gamma/PKC
      zeta-mediated TRB3 expression, which subsequently downregulated the gluconeogenic
      genes for glucose-6-phosphatase (G6Pase) and phosphoenol pyruvate carboxykinase 1
      in hepatocytes. We therefore conclude that suppression of IP modulation of
      hepatic gluconeogenesis through the PKA/CREB and PI3K-gamma/PKC-zeta/TRB3/AKT
      pathways contributes to the effects of NSAIDs in diabetes.

PMID- 24722248
TI  - MicroRNA-29 fine-tunes the expression of key FOXA2-activated lipid metabolism
      genes and is dysregulated in animal models of insulin resistance and diabetes.
AB  - MicroRNAs (miRNAs) have emerged as biomarkers of metabolic status, etiological
      factors in complex disease, and promising drug targets. Recent reports suggest
      that miRNAs are critical regulators of pathways underlying the pathophysiology of
      type 2 diabetes. In this study, we demonstrate by deep sequencing and real-time
      quantitative PCR that hepatic levels of Foxa2 mRNA and miR-29 are elevated in a
      mouse model of diet-induced insulin resistance. We also show that Foxa2 and miR
      29 are significantly upregulated in the livers of Zucker diabetic fatty (fa/fa)
      rats and that the levels of both returned to normal upon treatment with the
      insulin-sensitizing agent pioglitazone. We present evidence that miR-29
      expression in human hepatoma cells is controlled in part by FOXA2, which is known
      to play a critical role in hepatic energy homeostasis. Moreover, we demonstrate
      that miR-29 fine-tunes FOXA2-mediated activation of key lipid metabolism genes,
      including PPARGC1A, HMGCS2, and ABHD5. These results suggest that miR-29 is an
      important regulatory factor in normal metabolism and may represent a novel
      therapeutic target in type 2 diabetes and related metabolic syndromes.

PMID- 24722249
TI  - Pleiotropic effects of lipid genes on plasma glucose, HbA1c, and HOMA-IR levels.
AB  - Dyslipidemia is strongly associated with raised plasma glucose levels and insulin
      resistance (IR), and genome-wide association studies have identified 95 loci that
      explain a substantial proportion of the variance in blood lipids. However, the
      loci's effects on glucose-related traits are largely unknown. We have studied
      these lipid loci and tested their association collectively and individually with
      fasting plasma glucose (FPG), glycated hemoglobin (HbA1c), and IR in two
      independent cohorts: 10,995 subjects from LifeLines Cohort Study and 2,438
      subjects from Prevention of Renal and Vascular Endstage Disease (PREVEND) study.
      In contrast to the positive relationship between dyslipidemia and glucose traits,
      the genetic predisposition to dyslipidemia showed a pleiotropic lowering effect
      on glucose traits. Specifically, the genetic risk score related to higher
      triglyceride level was correlated with lower levels of FPG (P = 9.6 * 10(-10) and
      P = 0.03 in LifeLines and PREVEND, respectively), HbA1c (P = 4.2 * 10(-7) in
      LifeLines), and HOMA of estimated IR (P = 6.2 * 10(-4) in PREVEND), after
      adjusting for blood lipid levels. At the single nucleotide polymorphism level, 15
      lipid loci showed a pleiotropic association with glucose traits (P < 0.01), of
      which eight (CETP, MLXIPL, PLTP, GCKR, APOB, APOE-C1-C2, CYP7A1, and TIMD4) had
      opposite allelic directions of effect on dyslipidemia and glucose levels. Our
      findings suggest a complex genetic regulation and metabolic interplay between
      lipids and glucose. 

PMID- 24722250
TI  - KSRP ablation enhances brown fat gene program in white adipose tissue through
      reduced miR-150 expression.
AB  - Brown adipose tissue oxidizes chemical energy for heat generation and energy
      expenditure. Promoting brown-like transformation in white adipose tissue (WAT) is
      a promising strategy for combating obesity. Here, we find that targeted deletion
      of KH-type splicing regulatory protein (KSRP), an RNA-binding protein that
      regulates gene expression at multiple levels, causes a reduction in body
      adiposity. The expression of brown fat-selective genes is increased in
      subcutaneous/inguinal WAT (iWAT) of Ksrp(-/-) mice because of the elevated
      expression of PR domain containing 16 and peroxisome proliferator-activated
      receptor gamma coactivator 1alpha, which are key regulators promoting the brown
      fat gene program. The expression of microRNA (miR)-150 in iWAT is decreased due
      to impaired primary miR-150 processing in the absence of KSRP. We show that miR
      150 directly targets and represses Prdm16 and Ppargc1a, and that forced
      expression of miR-150 attenuates the elevated expression of brown fat genes
      caused by KSRP deletion. This study reveals the in vivo function of KSRP in
      controlling brown-like transformation of iWAT through post-transcriptional
      regulation of miR-150 expression.

PMID- 24722251
TI  - Recommendations for the definition of clinical responder in insulin preservation
      studies.
AB  - Clinical responder studies should contribute to the translation of effective
      treatments and interventions to the clinic. Since ultimately this translation
      will involve regulatory approval, we recommend that clinical trials prespecify a
      responder definition that can be assessed against the requirements and
      suggestions of regulatory agencies. In this article, we propose a clinical
      responder definition to specifically assist researchers and regulatory agencies
      in interpreting the clinical importance of statistically significant findings for
      studies of interventions intended to preserve beta-cell function in newly
      diagnosed type 1 diabetes. We focus on studies of 6-month beta-cell preservation
      in type 1 diabetes as measured by 2-h-stimulated C-peptide. We introduce criteria
      (bias, reliability, and external validity) for the assessment of responder
      definitions to ensure they meet U.S. Food and Drug Administration and European
      Medicines Agency guidelines. Using data from several published TrialNet studies,
      we evaluate our definition (no decrease in C-peptide) against published
      alternatives and determine that our definition has minimum bias with external
      validity. We observe that reliability could be improved by using changes in C
      peptide later than 6 months beyond baseline. In sum, to support efficacy claims
      of beta-cell preservation therapies in type 1 diabetes submitted to U.S. and
      European regulatory agencies, we recommend use of our definition. 

PMID- 24722252
TI  - PRKAR1B mutation associated with a new neurodegenerative disorder with unique
      pathology.
AB  - Pathological accumulation of intermediate filaments can be observed in
      neurodegenerative disorders, such as Alzheimer's disease, frontotemporal dementia
      and Parkinson's disease, and is also characteristic of neuronal intermediate
      filament inclusion disease. Intermediate filaments type IV include three
      neurofilament proteins (light, medium and heavy molecular weight neurofilament
      subunits) and alpha-internexin. The phosphorylation of intermediate filament
      proteins contributes to axonal growth, and is regulated by protein kinase A. Here
      we describe a family with a novel late-onset neurodegenerative disorder
      presenting with dementia and/or parkinsonism in 12 affected individuals. The
      disorder is characterized by a unique neuropathological phenotype displaying
      abundant neuronal inclusions by haematoxylin and eosin staining throughout the
      brain with immunoreactivity for intermediate filaments. Combining linkage
      analysis, exome sequencing and proteomics analysis, we identified a heterozygous
      c.149T>G (p.Leu50Arg) missense mutation in the gene encoding the protein kinase A
      type I-beta regulatory subunit (PRKAR1B). The pathogenicity of the mutation is
      supported by segregation in the family, absence in variant databases, and the
      specific accumulation of PRKAR1B in the inclusions in our cases associated with a
      specific biochemical pattern of PRKAR1B. Screening of PRKAR1B in 138 patients
      with Parkinson's disease and 56 patients with frontotemporal dementia did not
      identify additional novel pathogenic mutations. Our findings link a pathogenic
      PRKAR1B mutation to a novel hereditary neurodegenerative disorder and suggest an
      altered protein kinase A function through a reduced binding of the regulatory
      subunit to the A-kinase anchoring protein and the catalytic subunit of protein
      kinase A, which might result in subcellular dislocalization of the catalytic
      subunit and hyperphosphorylation of intermediate filaments. 

PMID- 24722253
TI  - Mycobacterium tuberculosis Rv3402c enhances mycobacterial survival within
      macrophages and modulates the host pro-inflammatory cytokines production via NF
      kappa B/ERK/p38 signaling.
AB  - Intracellular survival plays a central role in the pathogenesis of Mycobacterium
      tuberculosis, a process which depends on an array of virulence factors to
      colonize and replicate within the host. The M. tuberculosis iron regulated open
      reading frame (ORF) rv3402c, encoding a conserved hypothetical protein, was shown
      to be up-regulated upon infection in both human and mice macrophages. To explore
      the function of this ORF, we heterologously expressed the rv3402c gene in the non
      pathogenic fast-growing Mycobacterium smegmatis strain, and demonstrated that
      Rv3402c, a cell envelope-associated protein, was able to enhance the
      intracellular survival of recombinant M. smegmatis. Enhanced growth was not found
      to be the result of an increased resistance to intracellular stresses, as growth
      of the Rv3402c expressing strain was unaffected by iron depletion, H2O2 exposure,
      or acidic conditions. Colonization of macrophages by M. smegmatis expressing
      Rv3402c was associated with substantial cell death and significantly greater
      amount of TNF-alpha and IL-1beta compared with controls. Rv3402c-induced TNF
      alpha and IL-1beta production was found to be mediated by NF-kappaB, ERK and p38
      pathway in macrophages. In summary, our study suggests that Rv3402c delivered in
      a live M. smegmatis vehicle can modify the cytokines profile of macrophage,
      promote host cell death and enhance the persistence of mycobacterium within host
      cells. 

PMID- 24722254
TI  - Functional genomics evidence unearths new moonlighting roles of outer ring coat
      nucleoporins.
AB  - There is growing evidence for the involvement of Y-complex nucleoporins (Y-Nups)
      in cellular processes beyond the inner core of nuclear pores of eukaryotes. To
      comprehensively assess the range of possible functions of Y-Nups, we delimit
      their structural and functional properties by high-specificity sequence profiles
      and tissue-specific expression patterns. Our analysis establishes the presence of
      Y-Nups across eukaryotes with novel composite domain architectures, supporting
      new moonlighting functions in DNA repair, RNA processing, signaling and mitotic
      control. Y-Nups associated with a select subset of the discovered domains are
      found to be under tight coordinated regulation across diverse human and mouse
      cell types and tissues, strongly implying that they function in conjunction with
      the nuclear pore. Collectively, our results unearth an expanded network of Y-Nup
      interactions, thus supporting the emerging view of the Y-complex as a dynamic
      protein assembly with diverse functional roles in the cell. 

PMID- 24722256
TI  - Worsening preoperative heart failure is associated with mortality and noncardiac
      complications, but not myocardial infarction after noncardiac surgery: a
      retrospective cohort study.
AB  - BACKGROUND: Heart failure (HF) is an important risk factor for perioperative
      morbidity and mortality. While these patients are at high risk for cardiac
      adverse events, there are few current data describing the types of noncardiac
      complications that occur in this population. METHODS: We performed a multicenter
      cohort study of patients undergoing noncardiac surgery from 2005 to 2010 as part
      of the American College of Surgeons National Surgical Quality Improvement
      Program. A HF cohort (HF that is new or worsening within 30 days of surgery) was
      compared with a control cohort that was matched regarding other surgical risk
      factors. RESULTS: Five thousand ninety-four patients with worsening preoperative
      HF were compared with an otherwise similar cohort of patients without worsening
      preoperative HF. Worsening preoperative HF was associated with increased risk of
      30-day all-cause mortality (relative risk [RR] 2.08; 95% confidence interval
      [CI], 1.75-2.46; P < 0.001) and increased risk of morbidity (any recorded
      postoperative complication) (RR 1.54; 95% CI, 1.40-1.69; P < 0.001). HF patients
      had increased risk of developing renal failure (RR 1.85; 95% CI, 1.37-2.49; P <
      0.001), need for mechanical ventilation longer than 48 hours (RR 1.81; 95% CI,
      1.52-2.15; P < 0.001), pneumonia (RR 1.73; 95% CI, 1.44-2.08; P < 0.001), cardiac
      arrest (RR 1.69; 95% CI, 1.29-2.21; P < 0.001), unplanned intubation (RR 1.68;
      95% CI, 1.41-1.99; P < 0.001), renal insufficiency (RR 1.64; 95% CI, 1.10-2.44; P
      = 0.014), sepsis (RR 1.43, 95% CI, 1.24-1.64; P < 0.001), and urinary tract
      infection (RR 1.29; 95% CI, 1.06-1.58; P = 0.011). The incidence of myocardial
      infarction in the sample was similar between the 2 groups (RR 1.07; 95% CI, 0.75
      1.52; P = 0.719). CONCLUSIONS: Worsening preoperative HF is associated with a
      significant increase in postoperative morbidity and mortality when controlling
      for other comorbidities. Although these likely have a multifactorial etiology,
      patients are much more likely to suffer from respiratory, renal, and infectious
      complications than cardiac complications.

PMID- 24722255
TI  - The RNA-binding protein QKI suppresses cancer-associated aberrant splicing.
AB  - Lung cancer is the leading cause of cancer-related death worldwide. Aberrant
      splicing has been implicated in lung tumorigenesis. However, the functional links
      between splicing regulation and lung cancer are not well understood. Here we
      identify the RNA-binding protein QKI as a key regulator of alternative splicing
      in lung cancer. We show that QKI is frequently down-regulated in lung cancer, and
      its down-regulation is significantly associated with a poorer prognosis. QKI-5
      inhibits the proliferation and transformation of lung cancer cells both in vitro
      and in vivo. Our results demonstrate that QKI-5 regulates the alternative
      splicing of NUMB via binding to two RNA elements in its pre-mRNA, which in turn
      suppresses cell proliferation and prevents the activation of the Notch signaling
      pathway. We further show that QKI-5 inhibits splicing by selectively competing
      with a core splicing factor SF1 for binding to the branchpoint sequence. Taken
      together, our data reveal QKI as a critical regulator of splicing in lung cancer
      and suggest a novel tumor suppression mechanism involving QKI-mediated regulation
      of the Notch signaling pathway. 

PMID- 24722257
TI  - Relative influence on total cancelled operating room time from patients who are
      inpatients or outpatients preoperatively.
AB  - BACKGROUND: In previous studies, hospitals' operating room (OR) schedules were
      influenced markedly by decisions made within a few days of surgery. At least half
      of ORs had their last case scheduled or changed within 2 working days of surgery.
      In the current investigation, we studied whether many of these changes were due
      to patients who were admitted before surgery. We differentiated these
      "inpatients" from "outpatients" having ambulatory surgery or admitted on the day
      of surgery. METHODS: From 21 facilities of a nonacademic health system throughout
      the United States, N = 5 eight-week periods of cancellation data were obtained.
      From an academic hospital, N = 8 thirteen-week periods of cancellation data were
      obtained, including detailed audit data with timestamps of the entire
      scheduling/rescheduling/cancellation history for each case. RESULTS: (1) In the
      non-academic health system, outpatients accounted for 1.6% +/- 0.1% (SEM) of the
      scheduled minutes that were cancelled, whereas inpatients accounted for 8.1% +/-
      0.4%. Consequently, even though inpatients represented much less than half the
      total scheduled minutes of surgery (16.2% +/- 0.5%, P < 0.0001), they accounted
      for approximately half of the total cancelled minutes (overall P = 0.55, 49% +/-
      2%; hospitals only P = 0.062, 57% +/- 3%). (2) In the nonacademic health system,
      each 10% increase in a facility's percentage of outpatients making a physical
      visit to a preoperative clinic (versus only a preoperative phone call) was
      associated with a 0.0% +/- 0.1% absolute decrease in cancelled minutes (P =
      0.58). (3) In the academic hospital, inpatients accounted for 22.3% +/- 0.4% of
      the scheduled minutes but most of the total cancelled minutes (70% +/- 2%, P <
      0.0001). Slightly more than half the total inpatient cancelled minutes (54% +/-
      1%, P = 0.006) were due to cases scheduled within 1 workday prior to the day of
      surgery (e.g., Friday for Monday, Monday for Tuesday). During this period,
      inpatient cancellation rates, measured in minutes, were several-fold larger than
      outpatient rates (P < 0.0001). CONCLUSIONS: Facilities can achieve a <=2%
      cancellation rate for patients who are outpatient preoperatively with very few
      attending a preoperative clinic, when a virtual evaluation is carried out by
      phone. At least half of the cancelled time at health systems and hospitals is
      attributable to inpatients, and these patients principally are scheduled within 1
      workday of the day of surgery. This is why there are so many changes to the OR
      schedule within 1 workday before the day of surgery. Hospitals should evaluate
      the cost-effectiveness of earlier assessments of inpatients. In addition,
      scheduling office decision-making within 1 workday before surgery should be based
      on statistical forecasts that include the risks of cancellation and of inpatient
      add-on cases being scheduled. Hospitals should monitor the performance of their
      perioperative managers with respect to such behavior.

PMID- 24722258
TI  - A general purpose pharmacokinetic model for propofol.
AB  - BACKGROUND: Pharmacokinetic (PK) models are used to predict drug concentrations
      for infusion regimens for intraoperative displays and to calculate infusion rates
      in target-controlled infusion systems. For propofol, the PK models available in
      the literature were mostly developed from particular patient groups or anesthetic
      techniques, and there is uncertainty of the accuracy of the models under
      differing patient and clinical conditions. Our goal was to determine a PK model
      with robust predictive performance for a wide range of patient groups and
      clinical conditions. METHODS: We aggregated and analyzed 21 previously published
      propofol datasets containing data from young children, children, adults, elderly,
      and obese individuals. A 3-compartmental allometric model was estimated with
      NONMEM software using weight, age, sex, and patient status as covariates. A
      predictive performance metric focused on intraoperative conditions was devised
      and used along with the Akaike information criteria to guide model development.
      RESULTS: The dataset contains 10,927 drug concentration observations from 660
      individuals (age range 0.25-88 years; weight range 5.2-160 kg). The final model
      uses weight, age, sex, and patient versus healthy volunteer as covariates.
      Parameter estimates for a 35-year, 70-kg male patient were: 9.77, 29.0, 134 L,
      1.53, 1.42, and 0.608 L/min for V1, V2, V3, CL, Q2, and Q3, respectively.
      Predictive performance is better than or similar to that of specialized models,
      even for the subpopulations on which those models were derived. CONCLUSIONS: We
      have developed a single propofol PK model that performed well for a wide range of
      patient groups and clinical conditions. Further prospective evaluation of the
      model is needed.

PMID- 24722259
TI  - Nanoanesthesia: a novel, intravenous approach to ankle block in the rat by magnet
      directed concentration of ropivacaine-associated nanoparticles.
AB  - BACKGROUND: As an alternative to current methods of local nerve block, we studied
      the feasibility of producing ankle block in the rat with IV injection of magnetic
      nanoparticles (MNPs) associated with ropivacaine and application of a magnet at
      the ankle. METHODS: The anesthetic effect of magnet-directed ropivacaine
      associated MNPs (MNP/Ropiv) was tested in the rat using paw withdrawal latencies
      from thermal stimuli applied to the hindpaw. The MNP/Ropiv complexes consisted of
      0.7% w/v ropivacaine and 0.8% w/v MNPs containing 12% w/w magnetite (F3O4). The
      effect of IV injection of MNP/Ropiv with 15, 30, and 60-minute magnet application
      to the right ankle was compared with the effect without magnet application on the
      left hindpaw, to conventional ankle block with 0.1% or 0.2% ropivacaine, and to
      IV injection of MNPs alone with 30-minute magnet application to the right ankle.
      In addition, the pharmacokinetics of the MNP/Ropiv complexes were determined.
      RESULTS: IV injection of MNP/Ropiv with magnet application at the ankle
      significantly increased paw withdrawal latencies from thermal stimuli compared
      with pretreatment baselines in the same paw (P < 0.0001) and compared with the
      contralateral paw without magnet application (P < 0.0001). IV injection of MNPs
      alone had no significant effect on paw withdrawal latency. Absolute ropivacaine
      concentrations in ankle tissue, and ankle tissue-to-plasma concentration ratios
      were higher in the MNP/Ropiv group with 30-minute magnet application compared
      with MNP/Ropiv group without magnet application (mean +/- SEM, 150 +/- 10 ng/g vs
      105 +/- 15 ng/g, respectively, and 6.1 +/- 0.8 vs 4.2 +/- 0.7, respectively).
      CONCLUSIONS: The current study establishes proof of principle that it is possible
      to produce ankle block in the rat by IV injection of MNP/Ropiv complexes and
      magnet application at the ankle. The results indicate that further study of this
      approach is warranted.

PMID- 24722260
TI  - Dexmedetomidine reduces propofol and remifentanil requirements during bispectral
      index-guided closed-loop anesthesia: a double-blind, placebo-controlled trial.
AB  - BACKGROUND: The alpha2-adrenergic agonist dexmedetomidine is a sedative and can
      be used as an adjunct to anesthetics. Our primary goal was thus to determine the
      extent to which dexmedetomidine reduces the requirement for propofol and
      remifentanil. METHODS: This double-blinded, randomized study (NCT00921284) used
      an automated dual closed-loop administration to maintain the Bispectral Index
      between 40 and 60. Sixty-6 ASA physical status I and II patients were given
      either dexmedetomidine (1 MUg/kg over 10 minutes followed by a continuous
      infusion of 0.5 MUg/kg/h throughout surgery) or comparable volumes of saline as a
      placebo. Propofol and remifentanil requirements were compared using nonparametric
      tests and expressed as medians (interquartile ranges). RESULTS: Twenty-eight
      patients in each group completed the study. Patients given dexmedetomidine
      required less propofol (1.0 [0.7-1.3] vs 1.3 [1.0-1.7] mg/kg, P = 0.002) and
      remifentanil (1.2 [1.0-1.4] vs 1.6 [1.1-2.8] MUg/kg, P = 0.02) for anesthetic
      induction. The propofol dosage required for anesthetic maintenance was 29% (with
      a 95% confidence interval, 18-40) lower in patients given dexmedetomidine (2.2
      [1.5-3.0] vs 3.1 [2.4-4.5] mg/kg/h, P = 0.005), whereas the remifentanil dosage
      was not significantly different (0.16 [0.09-0.17] vs 0.14 [0.13-0.21] MUg/kg/h
      with P = 0.3). The incidence of adverse events, including hemodynamic instability
      and delayed recovery, was comparable with and without dexmedetomidine. The first
      postoperative request for morphine analgesia was delayed in patients given
      dexmedetomidine (median fourth hour vs first hour, P = 0.008). CONCLUSIONS:
      Dexmedetomidine administration significantly reduced the requirement for both
      propofol and remifentanil during anesthetic induction and reduced propofol use
      during maintenance of anesthesia. Dexmedetomidine also delayed postoperative
      analgesic use. Dexmedetomidine is a useful adjuvant that reduces anesthetic
      requirement and provides postoperative analgesia.

PMID- 24722261
TI  - A novel blood-sparing agent in cardiac surgery? First in-patient experience with
      the synthetic serine protease inhibitor MDCO-2010: a phase II, randomized, double
      blind, placebo-controlled study in patients undergoing coronary artery bypass
      grafting with cardiopulmonary bypass.
AB  - BACKGROUND: Antifibrinolytics have been used for 2 decades to reduce bleeding in
      cardiac surgery. MDCO-2010 is a novel, synthetic, serine protease inhibitor. We
      describe the first experience with this drug in patients. METHODS: In this phase
      II, double-blind, placebo-controlled study, 32 patients undergoing isolated
      primary coronary artery bypass grafting with cardiopulmonary bypass were randomly
      assigned to 1 of 5 increasing dosage groups of MDCO-2010. The primary aim was to
      evaluate pharmacokinetics (PK) with assessment of plasmatic concentrations of the
      drug, short-term safety, and tolerance of MDCO-2010. Secondary end points were
      influence on coagulation, chest tube drainage, and transfusion requirements.
      RESULTS: PK analysis showed linear dosage-proportional correlation between MDCO
      2010 infusion rate and PK parameters. Blood loss was significantly reduced in the
      3 highest dosage groups compared with control (P = 0.002, 0.004 and 0.011,
      respectively). The incidence of allogeneic blood product transfusions was lower
      with MDCO-2010 4/24 (17%) vs 4/8 (50%) in the control group. MDCO-2010 exhibited
      dosage-dependent antifibrinolytic effects through suppression of D-dimer
      generation and inhibition of tissue plasminogen activator-induced lysis in ROTEM
      analysis as well as anticoagulant effects demonstrated by prolongation of
      activated clotting time and activated partial thromboplastin time. No systematic
      differences in markers of end organ function were observed among treatment
      groups. Three patients in the MDCO-2010 groups experienced serious adverse
      events. One patient experienced intraoperative thrombosis of venous grafts
      considered possibly related to the study drug. No reexploration for mediastinal
      bleeding was required, and there were no deaths. CONCLUSIONS: This first-in
      patient study demonstrated dosage-proportional PK for MDCO-2010 and reduction of
      chest tube drainage and transfusions in patients undergoing primary coronary
      artery bypass grafting. Antifibrinolytic and anticoagulant effects were
      demonstrated using various markers of coagulation. MDCO-2010 was well tolerated
      and showed an acceptable initial safety profile. Larger multi-institutional
      studies are warranted to further investigate the safety and efficacy of this
      compound.

PMID- 24722262
TI  - Analysis of central mechanism of cognitive training on cognitive impairment after
      stroke: Resting-state functional magnetic resonance imaging study.
AB  - OBJECTIVE: To investigate the central mechanism of cognitive training in patients
      with stroke, using resting state (RS) functional magnetic resonance imaging
      (fMRI). METHODS: Patients with stroke and executive function and memory deficit
      were randomized to receive computer-assisted cognitive training (treatment group;
      total 60 h training over 10 weeks) or no training (control group). All
      participants received neuropsychological assessment and RS fMRI at baseline and
      10 weeks. RESULTS: Patients in the treatment group (n = 16) showed increased
      functional connectivity (FC) of the hippocampus with the frontal lobe (right
      inferior, right middle, left middle, left inferior and left superior frontal
      gyrus) and left parietal lobe at 10 weeks compared with baseline. Patients in the
      control group (n = 18) showed decreased FC of the left hippocampus-right
      occipital gyrus, and right hippocampus-right posterior lobe of cerebellum and
      left superior temporal gyrus. Significant correlations were found between
      improved neuropsychological scores and increased FC of the hippocampus with the
      frontal lobe and left parietal lobe in the treatment group only. CONCLUSIONS:
      Increased RS FC of the hippocampus with the frontal and parietal lobes may be an
      important mechanism of cognitive recovery after stroke.

PMID- 24722263
TI  - Increased arterial stiffness in systemic lupus erythematosus (SLE) patients at
      low risk for cardiovascular disease: a cross-sectional controlled study.
AB  - Cardiovascular disease (CVD) is a major cause of death in systemic lupus
      erythematosus (SLE) patients. Although the risk for cardiovascular events in
      patients with SLE is significant, the absolute number of events per year in any
      given cohort remains small. Thus, CVD risks stratification in patients with SLE
      focuses on surrogate markers for atherosclerosis at an early stage, such as
      reduced elasticity of arteries. Our study was designed to determine whether
      arterial stiffness is increased in SLE patients at low risk for CVD and analyze
      the role for traditional and non-traditional CVD risk factors on arterial
      stiffness in SLE. Carotid-femoral pulse wave velocity (PWV) was prospectively
      assessed as a measure of arterial stiffness in 41 SLE patients and 35 controls
      (CTL). Adjustment on age or Framingham score was performed using a logistic
      regression model. Factors associated with PWV were identified separately in SLE
      patients and in controls using Pearson's correlation coefficient for univariate
      analysis and multiple linear regression for multivariate analysis. SLE patients
      and controls displayed a low 10-year risk for CVD according to Framingham score
      (1.8+/-3.6% in SLE vs 1.6+/-2.8% in CTL, p = 0.46). Pulse wave velocity was,
      however, higher in SLE patients (7.1+/-1.6 m/s) as compared to controls (6.3+/
      0.8 m/s; p = 0.01, after Framingham score adjustment) and correlated with
      internal carotid wall thickness (p = 0.0017). In multivariable analysis, only
      systolic blood pressure (p = 0.0005) and cumulative dose of glucocorticoids (p =
      0.01) were associated with PWV in SLE patients. Interestingly, the link between
      systolic blood pressure (SBP) and arterial stiffness was also confirmed in SLE
      patients with normal systolic blood pressure. In conclusion, arterial stiffness
      is increased in SLE patients despite a low risk for CVD according to Framingham
      score and is associated with systolic blood pressure and glucocorticoid therapy. 

PMID- 24722264
TI  - Keeping the balance.
AB  - How we see our environment is the result of a multi-level, parallel processing
      effort by the central nervous system. This computation is initiated within the
      retina at the very first synapse in the visual pathway - the photoreceptor ribbon
      synapse. Two recent studies shed light on the critical role of balanced calcium
      channel activity in maturation of this highly specialized synapse. (1, 2.) 

PMID- 24722265
TI  - Tetraphenylporphyrin derivative specifically blocks members of the voltage-gated
      potassium channel subfamily Kv1.
AB  - Tetraphenylporphyrin derivatives represent a promising class of high-affinity
      ligands for voltage-gated potassium (Kv) channels. Herein, we investigated the
      mode of Kv channel block of one tetraphenylporphyrin derivative, por3, using
      electrophysiological methods, structure-based mutagenesis, and solid-state NMR
      spectroscopy. The combined data showed that por3 specifically blocks Kv1.x
      channels. Unexpectedly, 2 different por3 binding modes lead to Kv1.x channel
      block exerted through multiple por3 binding sites: first, por3 interacts in a
      highly cooperative and specific manner with the voltage sensor domain stabilizing
      closed Kv1 channel state(s). Therefore, stronger depolarization is needed to
      activate Kv1.x channels in the presence of por3. Second, por3 bind to a single
      site at the external pore entrance to block the ion conduction pathway of
      activated Kv1.x channels. This block is voltage-independent. Por3 appears to have
      equal affinities for voltage-sensor and pore. However, at negative voltage and
      low por3 concentration, por3 gating modifier properties prevail due to the high
      cooperativity of binding. By contrast, at positive voltages, when Kv1.x channels
      are fully activated, por3 pore blocking properties predominate. 

PMID- 24722267
TI  - DLS 5.0--the biomechanical effects of dynamic locking screws.
AB  - INTRODUCTION: Indirect reduction of dia-/metaphyseal fractures with minimally
      invasive implant application bridges the fracture zone in order to protect the
      soft-tissue and blood supply. The goal of this fixation strategy is to allow
      stable motion at the fracture site to achieve indirect bone healing with callus
      formation. However, concerns have arisen that the high axial stiffness and
      eccentric position of locked plating constructs may suppress interfragmentary
      motion and callus formation, particularly under the plate. The reason for this is
      an asymmetric fracture movement. The biological need for sufficient callus
      formation and secondary bone healing is three-dimensional micro movement in the
      fracture zone. The DLS was designed to allow for increased fracture site motion.
      The purpose of the current study was to determine the biomechanical effect of the
      DLS_5.0. METHODS: Twelve surrogate bone models were used for analyzing the
      characteristics of the DLS_5.0. The axial stiffness and the interfragmentary
      motion of locked plating constructs with DLS were compared to conventional
      constructs with Locking Head Screws (LS_5.0). A quasi-static axial load of 0 to
      2.5 kN was applied. Relative motion was measured. RESULTS: The dynamic system
      showed a biphasic axial stiffness distribution and provided a significant
      reduction of the initial axial stiffness of 74.4%. Additionally, the
      interfragmentary motion at the near cortex increased significantly from 0.033 mm
      to 0.210 mm (at 200N). CONCLUSIONS: The DLS may ultimately be an improvement over
      the angular stable plate osteosynthesis. The advantages of the angular stability
      are not only preserved but even supplemented by a dynamic element which leads to
      homogenous fracture movement and to a potentially uniform callus distribution.

PMID- 24722266
TI  - EGFRvIII-specific chimeric antigen receptor T cells migrate to and kill tumor
      deposits infiltrating the brain parenchyma in an invasive xenograft model of
      glioblastoma.
AB  - Glioblastoma (GBM) is the most common primary malignant brain tumor in adults and
      is uniformly lethal. T-cell-based immunotherapy offers a promising platform for
      treatment given its potential to specifically target tumor tissue while sparing
      the normal brain. However, the diffuse and infiltrative nature of these tumors in
      the brain parenchyma may pose an exceptional hurdle to successful immunotherapy
      in patients. Areas of invasive tumor are thought to reside behind an intact blood
      brain barrier, isolating them from effective immunosurveillance and thereby
      predisposing the development of "immunologically silent" tumor peninsulas.
      Therefore, it remains unclear if adoptively transferred T cells can migrate to
      and mediate regression in areas of invasive GBM. One barrier has been the lack of
      a preclinical mouse model that accurately recapitulates the growth patterns of
      human GBM in vivo. Here, we demonstrate that D-270 MG xenografts exhibit the
      classical features of GBM and produce the diffuse and invasive tumors seen in
      patients. Using this model, we designed experiments to assess whether T cells
      expressing third-generation chimeric antigen receptors (CARs) targeting the tumor
      specific mutation of the epidermal growth factor receptor, EGFRvIII, would
      localize to and treat invasive intracerebral GBM. EGFRvIII-targeted CAR
      (EGFRvIII+ CAR) T cells demonstrated in vitro EGFRvIII antigen-specific
      recognition and reactivity to the D-270 MG cell line, which naturally expresses
      EGFRvIII. Moreover, when administered systemically, EGFRvIII+ CAR T cells
      localized to areas of invasive tumor, suppressed tumor growth, and enhanced
      survival of mice with established intracranial D-270 MG tumors. Together, these
      data demonstrate that systemically administered T cells are capable of migrating
      to the invasive edges of GBM to mediate antitumor efficacy and tumor regression. 

PMID- 24722268
TI  - More about retinal disorders.

PMID- 24722269
TI  - Clinical profile and short-term outcomes of optic neuritis patients in India.
AB  - PURPOSE: To evaluate the clinical profile and short-term visual outcome of optic
      neuritis (ON) patients in India. MATERIALS AND METHODS: In this prospective study
      carried out over a period of 3 years, 99 eyes of 83 ON patients were examined and
      followed up for 10.8 +/- 8.2 months for type of presentation, recurrence rate,
      and visual outcome. RESULTS: Mean age was 27.6 +/- 8.8 years. Female
      preponderance was seen (70% of cases). Papillitis (53.5% of eyes) was more common
      than retrobulbar neuritis (46.5% of eyes). Bilateral presentation was seen in
      19.3% cases. Baseline median logMAR visual acuity (VA) was 1.6 +/- 0.8, which
      improved to 0.2 +/- 0.6, with approximately 64% of eyes retaining VA of 20/40 or
      more. Two patients had previous diagnosis of multiple sclerosis (MS). MS was
      newly diagnosed in two patients. Recurrence was seen in 16% of eyes and was more
      common in cases of retrobulbar neuritis. CONCLUSION: The clinical profile of ON
      in Indian patients is different from that in the Western population. Unlike
      reported in the Western literature, papillitis is frequent in the Indian setup,
      with lower recurrence rates but poorer outcomes.

PMID- 24722270
TI  - Manual cataract extraction via a subconjunctival limbus oblique incision for
      mature cataracts.
AB  - AIMS: To report the technique and outcomes of sutureless manual cataract
      extraction via a subconjunctival limbus oblique incision for mature cataracts.
      MATERIALS AND METHODS: This retrospective study comprised of 112 eyes of 83
      patients with mature cataract who all had manual cataract extraction via a
      subconjunctival limbus oblique incision. A transconjunctival tunnel is fashioned
      with a 3.0 mm keratome, 0.5 mm behind the limbal vascular arcades. A limbal
      tunnel, with a transverse extent of 9 mm in the cornea and 7.0 mm in the limbus,
      is created beneath the conjunctival/Tenon's tissue using an angled bevel-up
      crescent blade. Outcome measures included visual acuity, intraoperative
      complications, surgically induced astigmatism, endothelial cell loss rate and
      surgery time. RESULTS: Self-sealing wound was achieved in 112 eyes (98.2%). The
      nucleus was delivered in whole in 108 eyes (96.4%). Intraoperative complications
      included hyphema in 3 eyes (2.7%), iridodialysis in 2 eyes 1.8%), posterior
      capsular rupture and zonular dialysis in 2 eyes (1.8%). At the 3-month follow-up,
      91% patients achieved a best-corrected visual acuity of 20/20 or better, the mean
      of surgically induced astigmatism was -0.62 +/- 0.41 Diopters and endothelial
      cell loss was 4.2%. Average surgical time was 3.75 min per case. CONCLUSION: This
      subconjunctival limbus oblique incision has the potential to serve as safe and
      effective technique for mature cataracts.

PMID- 24722271
TI  - A rare case of toxic optic neuropathy secondary to consumption of neem oil.
AB  - A 35-year-old female was referred to our hospital with bilateral loss of vision
      of two days duration. She gave history of consumption of about 150 ml of neem oil
      five days back.Examination revealed no perception of light in both eyes. Both
      pupils were dilated and sluggishly reacting to light. Her fundus examination
      showed bilateral hyperemic, edematous discs and also edema extending along the
      superior and inferior temporal vascular arcade. Magnetic resonance imaging (MRI)
      scan showed bilateral putaminal regions with altered signal, hypointensities in
      T1-weighted images, hyperintensities on T2-weighted, images and hyperintense on
      Fluid Attenuation Inversion Recovery (FLAIR) images suggestive of cytotoxic edema
      due to tissue hypoxia. Her vision improved to 20/200 in both eyes with treatment
      after two months. This is the first case report of such nature in the literature
      to the best of our knowledge. 

PMID- 24722272
TI  - Excellent outcome of Aspergillous endophthalmitis in a case of allergic
      bronchopulmonary aspergillosis.
AB  - While invasive aspergillosis occurs typically in severely immunocompromised
      patients, cases of surgical site infections have been reported in immunocompetent
      individuals. The purpose is to report an eye with post-operative Aspergillus
      endophthalmitis, which achieved a good visual outcome following early and
      aggressive treatment. A young patient, known case of allergic bronchopulmonary
      aspergillosis presented to us with post-cataract surgery endophthalmitis. He was
      treated with pars plana vitrectomy and intravitreal voriconazole and systemic
      itraconazole. The patient regained a vision of 20/30 with follow up of 2 years. 

PMID- 24722273
TI  - Novel occurrence of axenfeld: Rieger syndrome in a patient with blepharophimosis
      ptosis epicanthus inversus syndrome.
AB  - Blepharophimosis ptosis epicanthus inversus syndrome (BPES) is a complex eyelid
      malformation characterized by the classical tetrad of blepharophimosis,
      telecanthus, ptosis, and epicanthus inversus. It has been reported to be
      associated with other ocular anomalies such as euryblepharon, strabismus,
      nystagmus, amblyopia, microphthalmos, lacrimal drainage apparatus abnormality,
      extra ocular muscle abnormalities, microcornea, trabecular dysgenesis, optic
      nerve hypoplasias, and colobomas of the optic disk. We describe a case of BPES
      with Axenfeld-Rieger syndrome, a neurocristopathy characterized by maldevelopment
      of the anterior segment with predisposition to development of glaucoma.
      Interestingly, both syndromes are caused by mutations in the same class of genes,
      namely the winged-helix/forked transcription factors (FOX) involved in a variety
      of developmental processes. 

PMID- 24722274
TI  - Annular elastolytic giant cell granuloma of conjunctiva: a case report.
AB  - Annular elastolytic giant cell granuloma is a condition characterized
      histologically by damaged elastic fibers associated with preponderance of giant
      cells along with absence of necrobiosis, lipid, mucin, and pallisading granuloma.
      It usually occurs on sun-damaged skin and hence the previous name actinic
      granuloma. A similar process occurs on the conjunctiva. Over the past three
      decades only four cases of conjunctival actinic granuloma have been documented.
      All the previous patients were females with lesions in nasal or temporal bulbar
      conjunctiva varying 2-3 mm in size. We report a male patient aged 70 years
      presenting with a 14 mm * 7 mm fleshy mass on right lower bulbar conjunctiva.
      Clinical differential diagnoses were lymphoma, squamous cell carcinoma in situ
      and amyloidosis. Surgical excision followed by histopathology confirmed it to be
      a case of actinic granuloma. This is the first case of isolated conjunctival
      actinic granuloma of such a large size reported from India. 

PMID- 24722275
TI  - Cunninghamella spinosum fungal corneal ulcer- first case report.

PMID- 24722276
TI  - Pseudoexfoliation on the posterior capsule.

PMID- 24722277
TI  - Polio survivor urges parents to choose vaccination.

PMID- 24722278
TI  - Acupuncture promotes angiogenesis after myocardial ischemia through H3K9
      acetylation regulation at VEGF gene.
AB  - BACKGROUND: Acupuncture exerts cardioprotective effects on several types of
      cardiac injuries, especially myocardial ischemia (MI), but the mechanisms have
      not yet been well elucidated. Angiogenesis mediated by VEGF gene expression and
      its modification through histone acetylation has been considered a target in
      treating myocardial ischemia. This study aims to exam whether modulation of
      angiogenesis through H3K9 acetylation regulation at VEGF gene is one possible
      cardioprotective mechanism of acupuncture. RESULTS: We generated rat MI models by
      ligating the left anterior descending coronary artery and applied
      electroacupuncture (EA) treatment at the Neiguan (PC6) acupoint. Our results
      showed that acupuncture reversed the S-T segment change, reduced Q-wave area,
      decreased CK, CK-MB, LDH levels, mitigated myocardial remodeling, and promoted
      microvessel formation in the MI heart. RNA-seq analysis showed that VEGF-induced
      angiogenesis signaling was involved in the modulation of EA. Western blot results
      verified that the protein expressions of VEGF, Ras, phospho-p44/42 MAPK, phospho
      p38 MAPK, phospho-SAPK/JNK and Akt, were all elevated significantly by EA
      treatment in the MI heart. Furthermore, increased H3K9 acetylation was also
      observed according with the VEGF. ChIP assay confirmed that EA treatment could
      notably stimulate the recruitment of H3K9ace at the VEGF promoter. CONCLUSIONS:
      Our study demonstrates for the first time that acupuncture can effectively up
      regulate VEGF expression through H3K9 acetylation modification directly at the
      VEGF promoter and hence activate VEGF-induced angiogenesis in rat MI models. We
      employed high throughput sequencing in this study and, for the first time,
      generated genome-wide gene expression profiles both in the rat MI model and in
      acupuncture treatment.

PMID- 24722279
TI  - Autophagy inhibitor LRPPRC suppresses mitophagy through interaction with
      mitophagy initiator Parkin.
AB  - Autophagy plays an important role in tumorigenesis. Mitochondrion-associated
      protein LRPPRC interacts with MAP1S that interacts with LC3 and bridges autophagy
      components with microtubules and mitochondria to affect autophagy flux.
      Dysfunction of LRPPRC and MAP1S is associated with poor survival of ovarian
      cancer patients. Furthermore, elevated levels of LRPPRC predict shorter overall
      survival in patients with prostate adenocarcinomas or gastric cancer. To
      understand the role of LRPPRC in tumor development, previously we reported that
      LRPPRC forms a ternary complex with Beclin 1 and Bcl-2 to inhibit autophagy. Here
      we further show that LRPPRC maintains the stability of Parkin that mono
      ubiquitinates Bcl-2 to increase Bcl-2 stability to inhibit autophagy. Under
      mitophagy stress, Parkin translocates to mitochondria to cause rupture of outer
      mitochondrial membrane and bind with exposed LRPPRC. Consequently, LRPPRC and
      Parkin help mitochondria being engulfed in autophagosomes to be degraded. In
      cells under long-term mitophagy stress, both LRPPRC and Parkin become depleted
      coincident with disappearance of mitochondria and final autophagy inactivation
      due to depletion of ATG5-ATG12 conjugates. LRPPRC functions as a checkpoint
      protein that prevents mitochondria from autophagy degradation and impact
      tumorigenesis. 

PMID- 24722280
TI  - Downregulation of FAP suppresses cell proliferation and metastasis through
      PTEN/PI3K/AKT and Ras-ERK signaling in oral squamous cell carcinoma.
AB  - It is largely recognized that fibroblast activation protein (FAP) is expressed in
      cancer-associated fibroblasts (CAFs) of many human carcinomas. Furthermore, FAP
      was recently also reported to be expressed in carcinoma cells of the breast,
      stomach, pancreatic ductal adenocarcinoma, colorectum, and uterine cervix. The
      carcinoma cell expression pattern of FAP has been described in several types of
      cancers, but the role of FAP in oral squamous cell carcinoma (OSCC) is unknown.
      The role of endogenous FAP in epithelium-derived tumors and molecular mechanisms
      has also not been reported. In this study, FAP was found to be expressed in
      carcinoma cells of OSCC and was upregulated in OSCC tissue samples compared with
      benign tissue samples using immunohistochemistry. In addition, its expression
      level was closely correlated with overall survival of patients with OSCC.
      Silencing FAP inhibited the growth and metastasis of OSCC cells in vitro and in
      vivo. Mechanistically, knockdown of FAP inactivated PTEN/PI3K/AKT and Ras-ERK and
      its downstream signaling regulating proliferation, migration, and invasion in
      OSCC cells, as the inhibitory effects of FAP on the proliferation and metastasis
      could be rescued by PTEN silencing. Our study suggests that FAP acts as an
      oncogene and may be a potential therapeutic target for patients with OSCC. 

PMID- 24722281
TI  - CGP37157, an inhibitor of the mitochondrial Na+/Ca2+ exchanger, protects neurons
      from excitotoxicity by blocking voltage-gated Ca2+ channels.
AB  - Inhibition of the mitochondrial Na(+)/Ca(2+) exchanger (NCLX) by CGP37157 is
      protective in models of neuronal injury that involve disruption of intracellular
      Ca(2+) homeostasis. However, the Ca(2+) signaling pathways and stores underlying
      neuroprotection by that inhibitor are not well defined. In the present study, we
      analyzed how intracellular Ca(2+) levels are modulated by CGP37157 (10 MUM)
      during NMDA insults in primary cultures of rat cortical neurons. We initially
      assessed the presence of NCLX in mitochondria of cultured neurons by
      immunolabeling, and subsequently, we analyzed the effects of CGP37157 on neuronal
      Ca(2+) homeostasis using cameleon-based mitochondrial Ca(2+) and cytosolic Ca(2+)
      ([Ca(2+)]i) live imaging. We observed that NCLX-driven mitochondrial Ca(2+)
      exchange occurs in cortical neurons under basal conditions as CGP37157 induced a
      decrease in [Ca(2)]i concomitant with a Ca(2+) accumulation inside the
      mitochondria. In turn, CGP37157 also inhibited mitochondrial Ca(2+) efflux after
      the stimulation of acetylcholine receptors. In contrast, CGP37157 strongly
      prevented depolarization-induced [Ca(2+)]i increase by blocking voltage-gated
      Ca(2+) channels (VGCCs), whereas it did not induce depletion of ER Ca(2+) stores.
      Moreover, mitochondrial Ca(2+) overload was reduced as a consequence of
      diminished Ca(2+) entry through VGCCs. The decrease in cytosolic and
      mitochondrial Ca(2+) overload by CGP37157 resulted in a reduction of excitotoxic
      mitochondrial damage, characterized here by a reduction in mitochondrial membrane
      depolarization, oxidative stress and calpain activation. In summary, our results
      provide evidence that during excitotoxicity CGP37157 modulates cytosolic and
      mitochondrial Ca(2+) dynamics that leads to attenuation of NMDA-induced
      mitochondrial dysfunction and neuronal cell death by blocking VGCCs. 

PMID- 24722282
TI  - Liver kinase B1 regulates the centrosome via PLK1.
AB  - Liver kinase B1 (LKB1) is a tumor suppressor mutationally inactivated in Peutz
      Jeghers syndrome (PJS) and various sporadic cancers. Although LKB1 encodes a
      kinase that possesses multiple functions, no individual hypothesis posed to date
      has convincingly explained how loss of LKB1 contributes to carcinogenesis. In
      this report we demonstrated that LKB1 maintains genomic stability through the
      regulation of centrosome duplication. We found that LKB1 colocalized with
      centrosomal proteins and was situated in the mitotic spindle pole. LKB1
      deficiency-induced centrosome amplification was independent of AMP-activated
      protein kinase (AMPK), a well-defined substrate of LKB1. Cells lacking LKB1
      exhibited an increase in phosphorylated and total Polo-like kinase 1 (PLK-1),
      NIMA-related kinase 2 (NEK2), and ninein-like protein (NLP). Overexpression of
      active PLK1 (T210D) reversed the inhibition of LKB1 on centrosome amplification.
      In contrast, depletion of PLK1 with siRNA or suppression of PLK1 kinase activity
      with BTO-1 (5-Cyano-7-nitro-2-benzothiazolecarboxamide-3-oxide) abrogated LKB1
      deficiency-induced centrosome amplification. We further characterized that LKB1
      phosphorylated and activated AMPK-related kinase 5 (NUAK1 or ARK5) that in turn
      increased the phosphorylation of MYPT1, enhanced the binding between MYPT1-PP1
      and PLK1, and conferred an effective dephosphorylation of PLK1. More importantly,
      we noted that LKB1-deficient cells exhibited multiple nuclear abnormalities, such
      as mitotic delay, binuclear, polylobed, grape, large, and micronuclear. Immediate
      depletion of LKB1 resulted in the accumulation of multiploidy cells. Expression
      of LKB1 is reversely correlated with the levels of PLK1 in human cancer tissues.
      Thus, we have uncovered a novel function of LKB1 in the maintenance of genomic
      stability through the regulation of centrosome mediated by PLK1. 

PMID- 24722283
TI  - Mutation of a Nopp140 gene dao-5 alters rDNA transcription and increases germ
      cell apoptosis in C. elegans.
AB  - Human diseases of impaired ribosome biogenesis resulting from disruption of rRNA
      biosynthesis or loss of ribosomal components are collectively described as
      'ribosomopathies'. Treacher Collins syndrome (TCS), a representative human
      ribosomopathy with craniofacial abnormalities, is attributed to mutations in the
      tcof1 gene that has a homologous gene called nopp140. Previous studies
      demonstrated that the dao-5 (dauer and aged animal overexpression gene 5) of
      Caenorhabditis elegans is a member of nopp140 gene family and plays a role in
      nucleogenesis in the early embryo. Here, we established a C. elegans model for
      studying Nopp140-associated ribosomopathy. A null dao-5 mutant ok542 with a semi
      infertile phenotype showed a delay in gonadogenesis, as well as a higher
      incidence of germline apoptosis. These phenotypes in dao-5(ok542) are likely
      resulted from inefficient rDNA transcription that was observed by run-on analyses
      and chromatin immunoprecipitation (ChIP) assays measuring the RNA Pol I occupancy
      on the rDNA promoter. ChIP assays further showed that the modifications of
      acetylated histone 4 (H4Ac) and dimethylation at the lysine 9 of histone 3
      (H3K9me2) around the rDNA promoter were altered in dao-5 mutants compared with
      the N2 wild type. In addition, activated CEP-1 (a C. elegans p53 homolog)
      activity was also linked to the loss of DAO-5 in terms of the transcriptional
      upregulation of two CEP-1 downstream effectors, EGL-1 and CED-13. We propose that
      the dao-5 mutant of C. elegans can be a valuable model for studying human Nopp140
      associated ribosomopathy at the cellular and molecular levels. 

PMID- 24722284
TI  - Met degradation by SAIT301, a Met monoclonal antibody, reduces the invasion and
      migration of nasopharyngeal cancer cells via inhibition of EGR-1 expression.
AB  - Nasopharyngeal carcinoma (NPC) is a common malignant tumor with high invasive and
      metastatic potential. The hepatocyte growth factor (HGF)-Met signaling pathway
      has a critical role in mediating the invasive growth of many different types of
      cancer, including head and neck squamous cell carcinoma. HGF also stimulates NPC
      cell growth and invasion in the cell line model. In this study, we determined the
      inhibitory effect of Met, using a Met-targeting monoclonal antibody (SAIT301), on
      the invasive and growth potential of NPC cell lines. Met inhibition by SAIT301
      resulted in highly significant inhibition of cell migration and invasion in both
      the HONE1 and HNE1 cell lines. In addition, we also found that co-treatment of
      SAIT301 and HGF decreased the anchorage-independent growth induced by HGF in HNE1
      cell lines. After SAIT301 treatment, Met, together with its downstream signaling
      proteins, showed downregulation of p-Met and p-ERK, but not p-AKT, in both HONE1
      and HNE1 cell lines. Interestingly, we found that HGF treatment of NPC cell lines
      induced early growth response protein (EGR-1) expression, which is involved in
      cell migration and invasion. In addition, co-treatment with SAIT301 and HGF
      inhibited the HGF-induced expression of EGR-1. Next, knockdown of EGR-1 using
      small-interfering RNA inhibited HGF-induced cell invasion in NPC cell lines,
      suggesting that the expression level of EGR-1 is important in HGF-induced cell
      invasion of NPC cells. Therefore, the results support that SAIT301 inhibited Met
      activation as well as the downstream EGR-1 expression and could have therapeutic
      potential in NPC. Taken together, we suggest that Met is an anticancer
      therapeutic target for NPC that warrants further investigation and clinical
      trials and SAIT301 may be a promising tool for NPC therapy. 

PMID- 24722285
TI  - Resistance to the tyrosine kinase inhibitor axitinib is associated with increased
      glucose metabolism in pancreatic adenocarcinoma.
AB  - Alterations in energy (glucose) metabolism are key events in the development and
      progression of cancer. In pancreatic adenocarcinoma (PDAC) cells, we investigated
      changes in glucose metabolism induced by resistance to the receptor tyrosine
      kinase inhibitor (RTKI) axitinib. Here, we show that human cell lines and mouse
      PDAC cell lines obtained from the spontaneous pancreatic cancer mouse model
      (Kras(G12D)Pdx1-cre) were sensitive to axitinib. The anti-proliferative effect
      was due to a G2/M block resulting in loss of 70-75% cell viability in the most
      sensitive PDAC cell line. However, a surviving sub-population showed a 2- to 3
      fold increase in [C-14]deoxyglucose ([C-14]DG) uptake. This was sustained in
      axitinib-resistant cell lines, which were derived from parental PDAC. In addition
      to the axitinib-induced increase in [C-14]DG uptake, we observed a translocation
      of glucose transporter-1 (Glut-1) transporters from cytosolic pools to the cell
      surface membrane and a 2-fold increase in glycolysis rates measured by the
      extracellular acidification rate (ECAR). We demonstrated an axitinib-induced
      increase in phosphorylated Protein Kinase B (pAkt) and by blocking pAkt with a
      phosphatidylinositol-3 kinase (PI3K) inhibitor we reversed the Glut-1
      translocation and restored sensitivity to axitinib treatment. Combination
      treatment with both axitinib and Akt inhibitor in parental pancreatic cell line
      resulted in a decrease in cell viability beyond that conferred by single therapy
      alone. Our study shows that PDAC resistance to axitinib results in increased
      glucose metabolism mediated by activated Akt. Combining axitinib and an Akt
      inhibitor may improve treatment in PDAC. 

PMID- 24722286
TI  - MicroRNA-181a-mediated downregulation of AC9 protein decreases intracellular cAMP
      level and inhibits ATRA-induced APL cell differentiation.
AB  - AC9 is one of the adenylate cyclase (AC) isoforms, which catalyze the conversion
      of ATP to cAMP, an important second messenger. We previously found that the
      integration of cAMP/PKA pathway with nuclear receptor-mediated signaling was
      required during all-trans retinoic acid (ATRA)-induced maturation of acute
      promyelocytic leukemia (APL) cells. Here we showed that AC9 could affect
      intracellular cAMP level and enhance the trans-activity of retinoic acid
      receptor. Knockdown of AC9 in APL cell line NB4 could obviously inhibit ATRA
      induced differentiation. We also demonstrated that miR-181a could decrease AC9
      expression by targeting 3'UTR of AC9 mRNA, finally controlling the production of
      intracellular cAMP. The expression of miR-181a itself could be inhibited by
      CEBPalpha, probably accounting for the differential expression of miR-181a in NB4
      and ATRA-resistant NB4-R1 cells. Moreover, we found that AC9 expression was
      relatively lower in newly diagnosed or relapsed APL patients than in both
      complete remission and non-leukemia cases, closely correlating with the
      leukemogenesis of APL. Taken together, our studies revealed for the first time
      the importance of miR-181a-mediated AC9 downregulation in APL. We also suggested
      the potential value of AC9 as a biomarker in the clinical diagnosis and treatment
      of leukemia. 

PMID- 24722287
TI  - Orally active microtubule-targeting agent, MPT0B271, for the treatment of human
      non-small cell lung cancer, alone and in combination with erlotinib.
AB  - Microtubule-binding agents, such as taxanes and vinca alkaloids, are used in the
      treatment of cancer. The limitations of these treatments, such as resistance to
      therapy and the need for intravenous administration, have encouraged the
      development of new agents. MPT0B271 (N-[1-(4-Methoxy-benzenesulfonyl)-2,3-dihydro
      1H-indol-7-yl]-1-oxy-isonicotinamide), an orally active microtubule-targeting
      agent, is a completely synthetic compound that possesses potent anticancer
      effects in vitro and in vivo. Tubulin polymerization assay and immunofluorescence
      experiment showed that MPT0B271 caused depolymerization of tubulin at both
      molecular and cellular levels. MPT0B271 reduced cell growth and viability at
      nanomolar concentrations in numerous cancer cell lines, including a multidrug
      resistant cancer cell line NCI/ADR-RES. Further studies indicated that MPT0B271
      is not a substrate of P-glycoprotein (P-gp), as determined by flow cytometric
      analysis of rhodamine-123 (Rh-123) dye efflux and the calcein acetoxymethyl ester
      (calcein AM) assay. MPT0B271 also caused G2/M cell-cycle arrest, accompanied by
      the up-regulation of cyclin B1, p-Thr161 Cdc2/p34, serine/threonine kinases polo
      like kinase 1, aurora kinase A and B and the downregulation of Cdc25C and p-Tyr15
      Cdc2/p34 protein levels. The appearance of MPM2 and the nuclear translocation of
      cyclin B1 denoted M phase arrest in MPT0B271-treated cells. Moreover, MPT0B271
      induced cell apoptosis in a concentration-dependent manner; it also reduced the
      expression of Bcl-2, Bcl-xL, and Mcl-1 and increased the cleavage of caspase-3
      and -7 and poly (ADP-ribose) polymerase (PARP). Finally, this study demonstrated
      that MPT0B271 in combination with erlotinib significantly inhibits the growth of
      the human non-small cell lung cancer A549 cells as compared with erlotinib
      treatment alone, both in vitro and in vivo. These findings identify MPT0B271 as a
      promising new tubulin-binding compound for the treatment of various cancers. 

PMID- 24722288
TI  - The Armc10/SVH gene: genome context, regulation of mitochondrial dynamics and
      protection against Abeta-induced mitochondrial fragmentation.
AB  - Mitochondrial function and dynamics are essential for neurotransmission, neural
      function and neuronal viability. Recently, we showed that the eutherian-specific
      Armcx gene cluster (Armcx1-6 genes), located in the X chromosome, encodes for a
      new family of proteins that localise to mitochondria, regulating mitochondrial
      trafficking. The Armcx gene cluster evolved by retrotransposition of the Armc10
      gene mRNA, which is present in all vertebrates and is considered to be the
      ancestor gene. Here we investigate the genomic organisation, mitochondrial
      functions and putative neuroprotective role of the Armc10 ancestor gene. The
      genomic context of the Armc10 locus shows considerable syntenic conservation
      among vertebrates, and sequence comparisons and CHIP-data suggest the presence of
      at least three conserved enhancers. We also show that the Armc10 protein
      localises to mitochondria and that it is highly expressed in the brain.
      Furthermore, we show that Armc10 levels regulate mitochondrial trafficking in
      neurons, but not mitochondrial aggregation, by controlling the number of moving
      mitochondria. We further demonstrate that the Armc10 protein interacts with the
      KIF5/Miro1-2/Trak2 trafficking complex. Finally, we show that overexpression of
      Armc10 in neurons prevents Abeta-induced mitochondrial fission and neuronal
      death. Our data suggest both conserved and differential roles of the Armc10/Armcx
      gene family in regulating mitochondrial dynamics in neurons, and underscore a
      protective effect of the Armc10 gene against Abeta-induced toxicity. Overall, our
      findings support a further degree of regulation of mitochondrial dynamics in the
      brain of more evolved mammals. 

PMID- 24722289
TI  - Selective inhibition of protein kinase C beta2 attenuates the adaptor P66 Shc
      mediated intestinal ischemia-reperfusion injury.
AB  - Apoptosis is a major mode of cell death occurring during ischemia-reperfusion
      (I/R) induced injury. The p66(Shc) adaptor protein, which is mediated by PKCbeta,
      has an essential role in apoptosis under oxidative stress. This study aimed to
      investigate the role of PKCbeta2/p66(Shc) pathway in intestinal I/R injury. In
      vivo, ischemia was induced by superior mesenteric artery occlusion in mice.
      Ruboxistaurin (PKCbeta inhibitor) or normal saline was administered before
      ischemia. Then blood and gut tissues were collected after reperfusion for various
      measurements. In vitro, Caco-2 cells were challenged with hypoxia-reoxygenation
      (H/R) to simulate intestinal I/R. Translocation and activation of PKCbeta2 were
      markedly induced in the I/R intestine. Ruboxistaurin significantly attenuated gut
      damage and decreased the serum levels of tumor necrosis factor-alpha (TNF-alpha)
      and interleukin-6 (IL-6). Pharmacological blockade of PKCbeta2 suppressed
      p66(Shc) overexpression and phosphorylation in the I/R intestine. Gene knockdown
      of PKCbeta2 via small interfering RNA (siRNA) inhibited H/R-induced p66(Shc)
      overexpression and phosphorylation in Caco-2 cells. Phorbol 12-myristate 13
      acetate (PMA), which stimulates PKCs, induced p66(Shc) phosphorylation and this
      was inhibited by ruboxistaurin and PKCbeta2 siRNA. Ruboxistaurin attenuated gut
      oxidative stress after I/R by suppressing the decreased expression of manganese
      superoxide dismutase (MnSOD), the exhaustion of the glutathione (GSH) system, and
      the overproduction of malondialdehyde (MDA). As a consequence, ruboxistaurin
      inhibited intestinal mucosa apoptosis after I/R. Therefore, PKCbeta2 inhibition
      protects mice from gut I/R injury by suppressing the adaptor p66(Shc)-mediated
      oxidative stress and subsequent apoptosis. This may represent a novel therapeutic
      approach for the prevention of intestinal I/R injury. 

PMID- 24722290
TI  - Expression of human cationic trypsinogen (PRSS1) in murine acinar cells promotes
      pancreatitis and apoptotic cell death.
AB  - Hereditary pancreatitis (HP) is an autosomal dominant disease that displays the
      features of both acute and chronic pancreatitis. Mutations in human cationic
      trypsinogen (PRSS1) are associated with HP and have provided some insight into
      the pathogenesis of pancreatitis, but mechanisms responsible for the initiation
      of pancreatitis have not been elucidated and the role of apoptosis and necrosis
      has been much debated. However, it has been generally accepted that trypsinogen,
      prematurely activated within the pancreatic acinar cell, has a major role in the
      initiation process. Functional studies of HP have been limited by the absence of
      an experimental system that authentically mimics disease development. We
      therefore developed a novel transgenic murine model system using wild-type (WT)
      human PRSS1 or two HP-associated mutants (R122H and N29I) to determine whether
      expression of human cationic trypsinogen in murine acinar cells promotes
      pancreatitis. The rat elastase promoter was used to target transgene expression
      to pancreatic acinar cells in three transgenic strains that were generated:
      Tg(Ela-PRSS1)NV, Tg(Ela-PRSS1*R122H)NV and Tg(Ela-PRSS1*N29I)NV. Mice were
      analysed histologically, immunohistochemically and biochemically. We found that
      transgene expression is restricted to pancreatic acinar cells and transgenic
      PRSS1 proteins are targeted to the pancreatic secretory pathway. Animals from all
      transgenic strains developed pancreatitis characterised by acinar cell
      vacuolisation, inflammatory infiltrates and fibrosis. Transgenic animals also
      developed more severe pancreatitis upon treatment with low-dose cerulein than
      controls, displaying significantly higher scores for oedema, inflammation and
      overall histopathology. Expression of PRSS1, WT or mutant, in acinar cells
      increased apoptosis in pancreatic tissues and isolated acinar cells. Moreover,
      studies of isolated acinar cells demonstrated that transgene expression promotes
      apoptosis rather than necrosis. We therefore conclude that expression of WT or
      mutant human PRSS1 in murine acinar cells induces apoptosis and is sufficient to
      promote spontaneous pancreatitis, which is enhanced in response to cellular
      insult. 

PMID- 24722291
TI  - Preclinical anti-arthritic study and pharmacokinetic properties of a potent
      histone deacetylase inhibitor MPT0G009.
AB  - The pathology of rheumatoid arthritis includes synoviocyte proliferation and
      inflammatory mediator expression, which may result from dysregulated epigenetic
      control by histone deacetylase (HDAC). Thus, HDAC inhibitors may be useful for
      treating inflammatory disease. This was a preclinical study of the HDAC
      inhibitor, MPT0G009. The IC50 values of MPT0G009 for HDAC1, 2, 3, 6 and 8
      enzymatic activities were significantly lower than those for the currently
      marketed HDAC inhibitor suberoylanilide hydroxamic acid (SAHA; vorinostat). In
      addition, MPT0G009 markedly inhibited cytokine secretion and macrophage colony
      stimulating factor/receptor activator of nuclear factor kappa B ligand-induced
      osteoclastogenesis by macrophages (50 ng/ml each). These MPT0G009 effects on
      cytokine secretion and osteoclast formation were reduced by the overexpression of
      HDAC 1 (class I HDAC) and 6 (class II HDAC) in cells, suggesting that these
      effects were due to the inhibition of its activity. In an in vivo rat model, oral
      administration of MPT0G009 (25 mg/kg) significantly inhibited paw swelling and
      bone destruction. Furthermore, compared with SAHA, MPT0G009 exhibited longer half
      life (9.53 h for oral administration) and higher oral bioavailability (13%) in
      rats. These results established the preclinical anti-arthritic efficacy and
      pharmacokinetic parameters of MPT0G009, which may provide a new therapeutic
      approach for treating inflammatory arthritis.

PMID- 24722292
TI  - Autocrine CSF-1R signaling drives mesothelioma chemoresistance via AKT
      activation.
AB  - Clinical management of malignant pleural mesothelioma (MPM) is very challenging
      because of the uncommon resistance of this tumor to chemotherapy. We report here
      increased expression of macrophage colony-stimulating-factor-1-receptor (M
      CSF/CSF-1R) mRNA in mesothelioma versus normal tissue specimens and demonstrate
      that CSF-1R expression identifies chemoresistant cells of mesothelial nature in
      both primary cultures and mesothelioma cell lines. By using RNAi or ligand
      trapping, we demonstrate that the chemoresistance properties of those cells
      depend on autocrine CSF-1R signaling. At the single-cell level, the isolated CSF
      1R(pos) cells exhibit a complex repertoire of pluripotency, epithelial
      mesenchymal transition and detoxifying factors, which define a clonogenic,
      chemoresistant, precursor-like cell sub-population. The simple activation of CSF
      1R in untransformed mesothelial cells is sufficient to confer clonogenicity and
      resistance to pemetrexed, hallmarks of mesothelioma. In addition, this induced a
      gene expression profile highly mimicking that observed in the MPM cells
      endogenously expressing the receptor and the ligands, suggesting that CSF-1R
      expression is mainly responsible for the phenotype of the identified cell sub
      populations. The survival of CSF1R(pos) cells requires active AKT (v-akt murine
      thymoma viral oncogene homolog 1) signaling, which contributed to increased
      levels of nuclear, transcriptionally competent beta-catenin. Inhibition of AKT
      reduced the transcriptional activity of beta-catenin-dependent reporters and
      sensitized the cells to senescence-induced clonogenic death after pemetrexed
      treatment. This work expands what is known on the non-macrophage functions of CSF
      1R and its role in solid tumors, and suggests that CSF-1R signaling may have a
      critical pathogenic role in a prototypical, inflammation-related cancer such as
      MPM and therefore may represent a promising target for therapeutic intervention.

PMID- 24722293
TI  - Constitutive expression of murine c-FLIPR causes autoimmunity in aged mice.
AB  - Death receptor-mediated apoptosis is a key mechanism for the control of immune
      responses and dysregulation of this pathway may lead to autoimmunity. Cellular
      FLICE-inhibitory proteins (c-FLIPs) are known as inhibitors of death receptor
      mediated apoptosis. The only short murine c-FLIP splice variant is c-FLIPRaji (c
      FLIPR). To investigate the functional role of c-FLIPR in the immune system, we
      used the vavFLIPR mouse model constitutively expressing murine c-FLIPR in all
      hematopoietic compartments. Lymphocytes from these mice are protected against
      CD95-mediated apoptosis and activation-induced cell death. Young vavFLIPR mice
      display normal lymphocyte compartments, but the lymphocyte populations alter with
      age. We identified reduced levels of T cells and slightly higher levels of B
      cells in 1-year-old vavFLIPR mice compared with wild-type (WT) littermates.
      Moreover, both B and T cells from aged vavFLIPR animals show activated
      phenotypes. Sera from 1-year-old WT and transgenic animals were analysed for anti
      nuclear antibodies. Notably, elevated titres of these autoantibodies were
      detected in vavFLIPR sera. Furthermore, tissue damage in kidneys and lungs from
      aged vavFLIPR animals was observed, indicating that vavFLIPR mice develop a
      systemic lupus erythematosus-like phenotype with age. Taken together, these data
      suggest that c-FLIPR is an important modulator of apoptosis and enforced
      expression leads to autoimmunity. 

PMID- 24722294
TI  - Betulinic acid-induced mitochondria-dependent cell death is counterbalanced by an
      autophagic salvage response.
AB  - Betulinic acid (BetA) is a plant-derived pentacyclic triterpenoid that exerts
      potent anti-cancer effects in vitro and in vivo. It was shown to induce apoptosis
      via a direct effect on mitochondria. This is largely independent of proapoptotic
      BAK and BAX, but can be inhibited by cyclosporin A (CsA), an inhibitor of the
      permeability transition (PT) pore. Here we show that blocking apoptosis with
      general caspase inhibitors did not prevent cell death, indicating that
      alternative, caspase-independent cell death pathways were activated. BetA did not
      induce necroptosis, but we observed a strong induction of autophagy in several
      cancer cell lines. Autophagy was functional as shown by enhanced flux and
      degradation of long-lived proteins. BetA-induced autophagy could be blocked, just
      like apoptosis, with CsA, suggesting that autophagy is activated as a response to
      the mitochondrial damage inflicted by BetA. As both a survival and cell death
      role have been attributed to autophagy, autophagy-deficient tumor cells and mouse
      embryo fibroblasts were analyzed to determine the role of autophagy in BetA
      induced cell death. This clearly established BetA-induced autophagy as a survival
      mechanism and indicates that BetA utilizes an as yet-undefined mechanism to kill
      cancer cells. 

PMID- 24722295
TI  - Silencing of Jagged1 inhibits cell growth and invasion in colorectal cancer.
AB  - Dysregulated Notch signaling has a critical role in the tumorigenesis. Jagged1, a
      Notch ligand, is overexpressed in various human cancers. Recent studies revealed
      the involvement of Jagged1 in colorectal cancer (CRC) development. These basic
      studies provide a promising potential for inhibition of the Notch pathway for the
      treatment of CRC. Herein, we aimed to investigate the consequences of targeting
      Jagged1 using shRNA on CRC both in vitro and in vivo to test their potential to
      inhibit this key element for CRC treatment. We found that downregulation of
      Jagged1 with lentiviral Jagged1-shRNA resulted in decreased colon cancer cell
      viability in vitro, most likely mediated through reduced cell proliferation.
      Importantly, Jagged1 knockdown induced G0/G1 phase cell cycle arrest, with
      reduced Cyclin D1, Cyclin E and c-Myc expression. Silencing of Jagged1 reduced
      the migration and invasive capacity of the colon cancer cells in vitro.
      Furthermore, colon cancer cells with knockdown of Jagged1 had much slower growth
      rate than control cells in a xenograft mouse model in vivo, with a marked
      downregulation of cell proliferation markers (PCNA, Ki-67, and c-Myc) and
      metastasis markers (MMP-2 and MMP-9). These findings rationalize a mechanistic
      approach to CRC treatment based on Jagged1-targeted therapeutic development. 

PMID- 24722296
TI  - Cardiac hypertrophy is negatively regulated by miR-541.
AB  - Heart failure is a leading cause of death in aging population. Cardiac
      hypertrophy is an adaptive reaction of the heart against cardiac overloading, but
      continuous cardiac hypertrophy is able to induce heart failure. We found that the
      level of miR-541 was decreased in angiotensin II (Ang-II) treated cardiomyocytes.
      Enforced expression of miR-541 resulted in a reduced hypertrophic phenotype upon
      Ang-II treatment in cellular models. In addition, we generated miR-541 transgenic
      mice that exhibited a reduced hypertrophic response upon Ang-II treatment.
      Furthermore, we found miR-541 is the target of microphthalmia-associated
      transcription factor (MITF) in the hypertrophic pathway and MITF can negatively
      regulate the expression of miR-541 at the transcriptional levels. MITF(ce/ce)
      mice exhibited a reduced hypertrophic phenotype upon Ang-II treatment. Knockdown
      of MITF also results in a reduction of hypertrophic responses after Ang-II
      treatment. Knockdown of miR-541 can block the antihypertrophic effect of MITF
      knockdown in cardiomyocytes upon Ang-II treatment. This indicates that the effect
      of MITF on cardiac hypertrophy relies on the regulation of miR-541. Our present
      study reveals a novel cardiac hypertrophy regulating pathway that was composed of
      miR-541 and MITF. Modulation of their levels may provide a new approach for
      tackling cardiac hypertrophy. 

PMID- 24722298
TI  - BAG3 protein expression in melanoma metastatic lymph nodes correlates with
      patients' survival.

PMID- 24722297
TI  - MARCH5-mediated quality control on acetylated Mfn1 facilitates mitochondrial
      homeostasis and cell survival.
AB  - Mitochondrial dynamics and quality control have a central role in the maintenance
      of cellular integrity. Mitochondrial ubiquitin ligase membrane-associated RING-CH
      (MARCH5) regulates mitochondrial dynamics. Here, we show that mitochondrial
      adaptation to stress is driven by MARCH5-dependent quality control on acetylated
      Mfn1. Under mitochondrial stress conditions, levels of Mfn1 were elevated twofold
      and depletion of Mfn1 sensitized these cells to apoptotic death. Interestingly,
      overexpression of Mfn1 also promoted cell death in these cells, indicating that a
      fine tuning of Mfn1 levels is necessary for cell survival. MARCH5 binds Mfn1 and
      the MARCH5-dependent Mfn1 ubiquitylation was significantly elevated under
      mitochondrial stress conditions along with an increase in acetylated Mfn1. The
      acetylation-deficient K491R mutant of Mfn1 showed weak interaction with MARCH5 as
      well as reduced ubiquitylation. Neither was observed in the acetylation mimetic
      K491Q mutant. In addition, MARCH5-knockout mouse embryonic fibroblast and
      MARCH5(H43W)-expressing HeLa cells lacking ubiquitin ligase activity experienced
      rapid cell death upon mitochondrial stress. Taken together, a fine balance of
      Mfn1 levels is maintained by MARCH5-mediated quality control on acetylated Mfn1,
      which is crucial for cell survival under mitochondria stress conditions. 

PMID- 24722299
TI  - Postsynaptic scaffold protein Homer 1a protects against traumatic brain injury
      via regulating group I metabotropic glutamate receptors.
AB  - Traumatic brain injury (TBI) produces excessive glutamate, leading to
      excitotoxicity via the activation of glutamate receptors. Postsynaptic density
      scaffold proteins have crucial roles in mediating signal transduction from
      glutamate receptors to their downstream mediators. Therefore, studies on the
      mechanisms underlying regulation of excitotoxicity by scaffold proteins can
      uncover new treatments for TBI. Here, we demonstrated that the postsynaptic
      scaffold protein Homer 1a was neuroprotective against TBI in vitro and in vivo,
      and this neuroprotection was associated with its effects on group I metabotropic
      glutamate receptors (mGluRs). Upon further study, we found that Homer 1a mainly
      affected neuronal injury induced by mGluR1 activation after TBI and also
      influenced mGluR5 function when its activity was restored. The ability of Homer
      1a to disrupt mGluR-ERK signaling contributed to its ability to regulate the
      functions of mGluR1 and mGluR5 after traumatic injury. Intracellular Ca(2+) and
      PKC were two important factors involved in the mediation of mGluR-ERK signaling
      by Homer 1a. These results define Homer 1a as a novel endogenous neuroprotective
      agent against TBI. 

PMID- 24722300
TI  - Impaired mitochondrial respiration promotes dendritic branching via the AMPK
      signaling pathway.
AB  - Functional neuronal circuits require a constant remodeling of their network
      composed of highly interconnected neurons. The plasticity of synapses and the
      shaping of elaborated dendritic branches are energy demanding and therefore
      depend on an efficient mitochondrial oxidative phosphorylation (OXPHOS). The
      spatial and functional regulations of dendritic patterning occur also after cell
      fate specification; however, the molecular mechanisms underlying this complex
      process remain elusive. Here, we exploit the changes in dendritic architecture in
      highly branched neurons as a result of aberrant mitochondrial activity. In
      sensory neurons of Caenorhabditis elegans, genetic manipulations of mitochondrial
      complex I subunits cause an unexpected outgrowth of dendritic arbors and ectopic
      structures. The increased number of dendritic branches is coordinated through a
      specific signaling cascade rather than as a simple consequence of oxidative
      stress. On the basis of genetic and pharmacological evidence, we show that OXPHOS
      deficiency promotes branching through the activation of the AMP-activated protein
      kinase AMPK and the downstream target phosphoinositide 3-kinase PI3K. Taken
      together, our findings describe a well-defined signaling pathway that regulates
      dendritic outgrowth in conditions of compromised OXPHOS and the resulting AMPK
      activation. 

PMID- 24722301
TI  - Effect of structural remodeling (retraction and recoil) of the pipeline
      embolization device on aneurysm occlusion rate.
AB  - BACKGROUND AND PURPOSE: During endovascular treatment of unruptured aneurysms
      with the Pipeline Embolization Device, an oversized device is often selected to
      achieve better wall apposition; however, this device oversizing could be related
      to overelongation and possible delayed enlargement of the stented region. The
      purpose of this study is to investigate the relationship between oversize and
      treatment outcome. MATERIALS AND METHODS: The DynaCT images of 14 aneurysms
      treated by a single Pipeline Embolization Device were retrospectively analyzed.
      3D images of the deployed device were compared with those acquired at the 6-month
      follow-up for qualitative and quantitative evaluation. The diameter and length of
      the Pipeline Embolization Device were measured at both time points and compared
      for determination of the device changes. RESULTS: Structural changes of the
      device have been observed, and it was found that the Pipeline Embolization Device
      influences the vessel curvature in some cases. On average, it increases its
      diameter by 0.23 mm and decreases its length by 2.88 mm within 6 months of
      initial deployment. Excessive elongation beyond its nominal length is correlated
      with a lower aneurysm occlusion rate at the 6-month follow-up. CONCLUSIONS: Not
      only does a Pipeline Embolization Device reconstruct the aneurysm and parent
      artery, but its entire structure goes through a gradual remodeling process. The
      relative deformation between the device and the artery indicates suboptimal wall
      apposition. Device oversizing does not have a direct effect on shortening or
      recoil. The aneurysm occlusion rate, however, is lowered by overelongation of the
      Pipeline Embolization Device.

PMID- 24722303
TI  - Preoperative embolization of intracranial meningiomas: efficacy, technical
      considerations, and complications.
AB  - BACKGROUND AND PURPOSE: Preoperative embolization for intracranial meningiomas
      offers potential advantages for safer and more effective surgery. However, this
      treatment strategy has not been examined in a large comparative series. The
      purpose of this study was to review our experience using preoperative
      embolization to understand the efficacy, technical considerations and
      complications of this technique. MATERIALS AND METHODS: We performed a
      retrospective review of patients undergoing intracranial meningioma resection at
      our institution (March 2001 to December 2012). Comparisons were made between
      embolized and nonembolized patients, including patient and tumor characteristics,
      embolization method, operative blood loss, complications, and extent of
      resection. Logistic regression analyses were used to identify factors predictive
      of operative blood loss and extent of resection. RESULTS: Preoperatively, 224
      patients were referred for embolization, of which 177 received embolization. No
      complications were seen in 97.1%. There were no significant differences in
      operative duration, extent of resection, or complications. Estimated blood loss
      was higher in the embolized group (410 versus 315 mL, P=.0074), but history of
      embolization was not a predictor of blood loss in multivariate analysis.
      Independent predictors of blood loss included decreasing degree of tumor
      embolization (P=.037), skull base location (P=.005), and male sex (P=.034).
      Embolization was not an independent predictor of gross total resection.
      CONCLUSIONS: Preoperative embolization is a safe option for selected meningiomas.
      In our series, embolization did not alter the operative duration, complications,
      or degree of resection, but the degree of embolization was an independent
      predictor of decreased operative blood loss.

PMID- 24722302
TI  - Analysis of hemodynamics and aneurysm occlusion after flow-diverting treatment in
      rabbit models.
AB  - BACKGROUND AND PURPOSE: Predicting the outcome of flow diversion treatment of
      cerebral aneurysms remains challenging. Our aim was to investigate the
      relationship between hemodynamic conditions created immediately after flow
      diversion and subsequent occlusion of experimental aneurysms in rabbits.
      MATERIALS AND METHODS: The hemodynamic environment before and after flow
      diversion treatment of elastase-induced aneurysms in 20 rabbits was modeled by
      using image-based computational fluid dynamics. Local aneurysm occlusion was
      quantified by using a voxelization technique on 3D images acquired 8 weeks after
      treatment. Global and local voxel-by-voxel hemodynamic variables were used to
      statistically compare aneurysm regions that later thrombosed to regions that
      remained patent. RESULTS: Six aneurysms remained patent at 8 weeks, while 14 were
      completely or nearly completely occluded. Patent aneurysms had statistically
      larger neck sizes (P = .0015) and smaller mean transit times (P = .02). The
      velocity, vorticity, and shear rate were approximately 2.8 times (P < .0001)
      larger in patent regions-that is, they had larger "flow activity" than regions
      that progressed to occlusion. Statistical models based on local hemodynamic
      variables were capable of predicting local occlusion with good precision (84%
      accuracy), especially away from the neck (92%-94%). Predictions near the neck
      were poorer (73% accuracy). CONCLUSIONS: These results suggests that the dominant
      healing mechanism of occlusion within the aneurysm dome is related to slow-flow
      induced thrombosis, while near the neck, other processes could be at play
      simultaneously.

PMID- 24722304
TI  - Transition into driven equilibrium of the balanced steady-state free precession
      as an ultrafast multisection T2-weighted imaging of the brain.
AB  - BACKGROUND AND PURPOSE: Current T2-weighted imaging takes >3 minutes to perform,
      for which the ultrafast transition into driven equilibrium (TIDE) technique may
      be potentially helpful. This study qualitatively and quantitatively evaluates the
      imaging of transition into driven equilibrium of the balanced steady-state free
      precession (TIDE) compared with TSE and turbo gradient spin-echo on T2-weighted
      MR images. MATERIALS AND METHODS: Thirty healthy volunteers were examined with T2
      weighted images by using TIDE, TSE, and turbo gradient spin-echo sequences.
      Imaging was evaluated qualitatively by 2 independent observers on the basis of a
      4-point rating scale regarding contrast characteristics and artifacts behavior.
      Image SNR and contrast-to-noise ratio were quantitatively assessed. RESULTS: TIDE
      provided T2-weighted contrast similar to that in TSE and turbo gradient spin-echo
      with only one-eighth of the scan time. TIDE showed gray-white matter
      differentiation and iron-load sensitivity inferior that of TSE and turbo gradient
      spin-echo, but with improved motion artifacts reduction on qualitative scores.
      Nonmotion ghosting artifacts were uniquely found in TIDE images. The overall SNRs
      of TSE were 1.9-2.0 times those of turbo gradient spin-echo and 1.7-2.2 times of
      those of TIDE for brain tissue (P < .0001). TIDE had a higher contrast-to-noise
      ratio than TSE (P = .169) and turbo gradient spin-echo (P < .0001) regarding non
      iron-containing gray matter versus white matter. TIDE had a lower contrast-to
      noise ratio than turbo gradient spin-echo and TSE (P < .0001) between iron
      containing gray matter and white matter. CONCLUSIONS: TIDE provides T2-weighted
      images with reduced scan times and reduced motion artifacts compared with TSE and
      turbo gradient spin-echo with the trade-off of reduced SNR and poorer gray-white
      matter differentiation.

PMID- 24722305
TI  - High-resolution MRI vessel wall imaging: spatial and temporal patterns of
      reversible cerebral vasoconstriction syndrome and central nervous system
      vasculitis.
AB  - BACKGROUND AND PURPOSE: High-resolution MR imaging is an emerging tool for
      evaluating intracranial artery disease. It has an advantage of defining vessel
      wall characteristics of intracranial vascular diseases. We investigated high
      resolution MR imaging arterial wall characteristics of CNS vasculitis and
      reversible cerebral vasoconstriction syndrome to determine wall pattern changes
      during a follow-up period. MATERIALS AND METHODS: We retrospectively reviewed 3T
      high-resolution MR imaging vessel wall studies performed on 26 patients with a
      confirmed diagnosis of CNS vasculitis and reversible cerebral vasoconstriction
      syndrome during a follow-up period. Vessel wall imaging protocol included black
      blood contrast-enhanced T1-weighted sequences with fat suppression and a
      saturation band, and time-of-flight MRA of the circle of Willis. Vessel wall
      characteristics including enhancement, wall thickening, and lumen narrowing were
      collected. RESULTS: Thirteen patients with CNS vasculitis and 13 patients with
      reversible cerebral vasoconstriction syndrome were included. In the CNS
      vasculitis group, 9 patients showed smooth, concentric wall enhancement and
      thickening; 3 patients had smooth, eccentric wall enhancement and thickening; and
      1 patient was without wall enhancement and thickening. Six of 13 patients had
      follow-up imaging; 4 patients showed stable smooth, concentric enhancement and
      thickening; and 2 patients had resoluton of initial imaging findings. In the
      reversible cerebral vasoconstriction syndrome group, 10 patients showed diffuse,
      uniform wall thickening with negligible-to-mild enhancement. Nine patients had
      follow-up imaging, with 8 patients showing complete resolution of the initial
      findings. CONCLUSIONS: Postgadolinium 3T-high-resolution MR imaging appears to be
      a feasible tool in differentiating vessel wall patterns of CNS vasculitis and
      reversible cerebral vasoconstriction syndrome changes during a follow-up period.

PMID- 24722306
TI  - Critical findings: timing of notification in neuroradiology.
AB  - BACKGROUND AND PURPOSE: Timely reporting of critical findings in radiology has
      been identified by The Joint Commission as one of the National Patient Safety
      Goals. Our aim was to determine the magnitude of delays between identifying a
      neuroradiologic critical finding and verbally notifying the caregiver in an
      effort to improve clinical outcomes. MATERIALS AND METHODS: We surveyed the time
      of critical finding discovery, attempted notification, and direct communication
      between neuroradiologists and caregivers for weekday, evening, overnight, and
      weekend shifts during an 8-week period. The data were collected by trained
      observers and/or trainees and included 13 neuroradiology attendings plus fellows
      and residents. Critical findings were based on a previously approved 17-item
      list. Summary and comparative t test statistics were calculated, and sources of
      delays were identified. RESULTS: Ninety-one critical findings were recorded. The
      mean time from study acquisition to critical finding discovery was 62.2 minutes,
      from critical finding discovery to call made 3.7 minutes, and from call made to
      direct communication, 5.2 minutes. The overall time from critical finding
      discovery to caregiver notification was within 10 minutes in 72.5% (66/91) and 15
      minutes in 93.4% (85/91) of cases. There were no significant differences across
      shifts except for daytime versus overnight and weekend shifts, when means were
      2.4, 5.6, and 8.7 minutes, respectively (P < .01). If >1 physician was called,
      the mean notification time increased from 3.5 to 10.1 minutes (P < .01). Sources
      of delays included inaccurate contact information, physician unavailability
      (shift change/office closed), patient transfer to a different service, or lack of
      responsiveness from caregivers. CONCLUSIONS: Direct communication with the
      responsible referring physician occurred consistently within 10-15 minutes after
      observation of a critical finding. These delays are less than the average
      interval from study acquisition to critical finding discovery (mean, 62.2
      minutes).

PMID- 24722307
TI  - A novel flow-diverting device (Tubridge) for the treatment of 28 large or giant
      intracranial aneurysms: a single-center experience.
AB  - BACKGROUND AND PURPOSE: The Tubridge flow diverter is a novel device developed in
      China and aimed at reconstructing the parent artery and occluding the aneurysm.
      We conducted this study to evaluate its feasibility, safety, and efficacy for the
      treatment of large or giant internal carotid artery aneurysms, which are still
      challenging with conventional therapy. MATERIALS AND METHODS: The clinical and
      angiographic data of 28 patients with 28 large or giant internal carotid artery
      aneurysms treated with Tubridge flow diverters were prospectively collected and
      analyzed. RESULTS: Thirty-three Tubridge flow diverters were successfully
      implanted except for 1 poor midstent opening; the result was a technical success
      rate of 97.0% (32/33). Follow-up angiographies were available for 25 aneurysms;
      the mean follow-up was 9.9 months (5-24 months). Of the 25 aneurysms, 18 (72.0%)
      were completely occluded, 6 (24.0%) were improved, and 1 (4.0%) was unchanged.
      All of the visible covered branches and parent arteries were patent, with no
      stenosis or obliteration. During a follow-up of 6-30 months (mean, 19 months),
      symptoms were resolved in 13 patients, improved in 6 patients, and unchanged in 4
      patients. Five patients experienced transient clinical deterioration due to a
      postoperative increased mass effect. Procedure-related morbidity and mortality
      were both zero. CONCLUSIONS: Our preliminary experience shows that the Tubridge
      flow diverter is a safe and effective tool for treating large and giant internal
      carotid artery aneurysms. However, multicenter randomized trials and studies
      involving a long-term follow-up are necessary.

PMID- 24722308
TI  - Metabolic imaging of ischemic stroke: the present and future.
AB  - Measures of cerebral metabolism may be useful in the selection of patients for
      reperfusion therapies and as end points in clinical trials. However, there are
      currently no clinically routine techniques that provide such data directly. We
      review how imaging modalities in current clinical use may provide surrogate
      markers of metabolic activity. Promising techniques for metabolic imaging that
      are currently in the pipeline are reviewed.

PMID- 24722309
TI  - Fluoroscopic-guided lumbar puncture: fluoroscopic time and implications of body
      mass index--a baseline study.
AB  - BACKGROUND AND PURPOSE: Fluoroscopic-guided lumbar puncture is an effective
      alternative to bedside lumbar puncture in challenging patients. However, no
      published guidelines are available for an acceptable range of fluoroscopic time
      for this procedure. The purpose of this study was to set department benchmark
      fluoroscopic times for lumbar puncture, accounting for body mass index in our
      patient population. MATERIALS AND METHODS: We identified and reviewed all
      patients who underwent fluoroscopic-guided lumbar puncture at 4 hospitals during
      a 2-year period (July 2011 to June 2013). Data collection included patient
      information (demographics, body mass index, history of prior lumbar surgery
      and/or lumbar hardware, scoliosis); procedure details (fluoroscopic time, level
      of access, approach, needle gauge and length); level of operator experience; and
      hospital site. A generalized linear model was used to test whether body mass
      index influenced fluoroscopic time while controlling other factors. RESULTS: Five
      hundred eighty-four patients (mean age, 47.8 +/- 16.2 years; range, 16-92 years;
      33% male) had successful fluoroscopic-guided lumbar puncture s. Mean body mass
      index and fluoroscopic time were higher in female patients (34.4 +/- 9.9 kg/m(2)
      and 1.07 minutes; 95% CI, 0.95-1.20) than in male patients (29.2 +/- 7.3 kg/m(2)
      and 0.91 minutes; 95% CI, 0.79-1.03). Body mass index (P = .001), hospital site
      (P < .001), and level of experience (P = .03) were factors significantly
      affecting fluoroscopic time on multivariate analysis. Benchmark fluoroscopic
      times in minutes were the following: 0.48 (95% CI, 0.40-0.56) for normal, 0.61
      for overweight (95% CI, 0.52-0.71), 0.63(95% CI, 0.58-0.73) for obese, and 0.86
      (95% CI, 0.74-1.01) in extremely obese body mass index categories. CONCLUSIONS:
      In patients undergoing fluoroscopic-guided lumbar punctures, fluoroscopy time
      increased with body mass index We established benchmark fluoroscopic-guided
      lumbar puncture time ranges as related to body mass index in our patient
      population.

PMID- 24722310
TI  - Neuroimaging features and predictors of outcome in eclamptic encephalopathy: a
      prospective observational study.
AB  - BACKGROUND AND PURPOSE: Posterior reversible encephalopathy syndrome is
      associated with eclampsia. We assessed the distribution and nature of typical and
      atypical cranial MR imaging findings in these patients and their correlation with
      clinical and laboratory data and predictors of outcome. MATERIALS AND METHODS:
      Forty-five clinically confirmed cases of eclampsia were included in this
      prospective observational study. Subjects with hemolysis, elevated liver enzymes,
      and low platelets syndrome (n = 9) and pre-existing neurologic conditions (1 with
      cerebral solitary cysticercus granuloma) were excluded. Patients underwent blood
      investigations and cranial MR imaging. RESULTS: Twenty-seven patients had
      abnormal while 8 had normal MR imaging findings. Involvement of brain regions was
      as follows: frontal, 88.89%; temporal, 44.44%; parietal, 100%; occipital, 100%;
      deep gray matter, 29.63%; cerebellum, 22.22%; brain stem, 14.81%. Cytotoxic edema
      was present in 33.33% of cases; 66.67% of patients had mild posterior reversible
      encephalopathy syndrome; 25.92% had moderate posterior reversible encephalopathy
      syndrome; and 7.41% had severe posterior reversible encephalopathy syndrome.
      Abnormal neuroimaging findings were significantly associated with altered
      sensorium; visual disturbances; status epilepticus; and elevated serum
      creatinine, uric acid, and lactate dehydrogenase (P=.006, P=.018, P=.015, P=.019,
      P=.003, and P=.001, respectively). Serum creatinine, uric acid, and lactate
      dehydrogenase values and the presence of moderate or severe posterior reversible
      encephalopathy syndrome were significantly associated with mortality (P<.001,
      P<.001, P=.009, and P=.027, respectively). CONCLUSIONS: Neuroimaging in eclampsia
      demonstrates a higher incidence of atypical distributions and cytotoxic edema
      than previously thought. Altered sensorium; visual disturbances; status
      epilepticus; and elevated serum uric acid, lactate dehydrogenase, and creatinine
      are associated with abnormal neuroimaging findings. Higher serum creatinine, uric
      acid, and lactate dehydrogenase levels and moderate and severe forms of posterior
      reversible encephalopathy syndrome are possible predictors of poor outcome.

PMID- 24722311
TI  - Screening CT angiography for pediatric blunt cerebrovascular injury with emphasis
      on the cervical "seatbelt sign".
AB  - BACKGROUND AND PURPOSE: There are no standard screening guidelines to evaluate
      blunt cerebrovascular injury in children. The purpose of this retrospective study
      was to understand the clinical and radiologic risk factors associated with
      pediatric blunt cerebrovascular injury on CTA of the neck with primary attention
      to the cervical "seatbelt sign." MATERIALS AND METHODS: Radiology reports from
      2002 to 2012 were queried for the examination "CTA neck." The electronic medical
      record was reviewed for mechanism of injury, Glasgow Coma Scale score, and
      physical examination findings. Radiology reports from adjunct radiographic
      studies were reviewed. CTA neck examinations with reported blunt cerebrovascular
      injury were reviewed to confirm imaging findings. Patients with penetrating
      injury or those without a history of trauma were excluded. RESULTS: Four hundred
      sixty-three patients underwent CTA of the neck; 137 had blunt trauma. Forty-two
      of 85 patients involved in a motor vehicle collision had a cervical seatbelt
      sign; none had blunt cerebrovascular injury. Nine vessels (4 vertebral arteries,
      4 ICAs, 1 common carotid artery) in 8 patients ultimately were diagnosed with
      various grades (I-IV) of blunt cerebrovascular injury, representing 5.8% (8/137)
      of the population screened for blunt neck trauma. The mean Glasgow Coma Scale
      score was significantly lower (P=.02) in the blunt cerebrovascular injury group
      versus the non-blunt cerebrovascular injury group. Although not statistically
      significant, patients with blunt cerebrovascular injury had a higher tendency to
      have additional traumatic injuries, primarily basilar skull fractures (P=.05) and
      intracranial hemorrhage (P=.13). CONCLUSIONS: A common indication for neck CTA,
      the cervical seatbelt sign, was not associated with blunt cerebrovascular injury.
      With the exception of Glasgow Coma Scale score, no single risk factor was
      statistically significant in predicting vascular injury in this series.

PMID- 24722312
TI  - Brain structure and function in patients after metal-on-metal hip resurfacing.
AB  - BACKGROUND AND PURPOSE: Hip prostheses that use a metal-on-metal articulation
      expose the brain to elevated metal concentrations that, in acute excess due to
      prosthesis malfunction, is associated with neurologic damage, including visual
      and hearing loss and motor deficits. Here, we examined whether chronic exposure
      to lower elevated metal levels, typical of well-functioning prostheses, also
      affects brain structure and function. MATERIALS AND METHODS: We compared brain
      volumes, metal deposition, and gray matter attenuation by MR imaging and clinical
      neurologic function in patients 8 years after receiving a metal-on-metal hip
      resurfacing versus a matched group of patients with the same duration exposure to
      a conventional hip prosthesis. RESULTS: Twenty-nine patients (25 men; mean, age
      59+/-7 years) after metal-on-metal hip resurfacing and 29 patients (25 men; 59+/
      8 years) after total hip arthroplasty were compared. Whole blood cobalt and
      chromium concentrations were 5-10 times higher in the metal-on-metal hip
      resurfacing group (P<.0001). Occipital cortex gray matter attenuation tended to
      be lower (P<.005 uncorrected, P>.05 corrected), and the optic chiasm area tended
      to be lower (mean difference, -2.7 mm2; P=.076) in the metal-on-metal hip
      resurfacing group. Subgroup analyses in 34 patients (17 per group), after
      exclusion of primary ocular pathology, showed the same trend in gray matter
      attenuation in the occipital cortex and basal ganglia and a smaller optic chiasm
      in the metal-on-metal hip resurfacing group (mean difference, -3.9 mm2; P=.048).
      No other structural or functional differences were found between the groups.
      CONCLUSIONS: Chronic exposure to metal-on-metal hip resurfacing is associated
      with subtle structural change in the visual pathways and the basal ganglia in
      asymptomatic patients.

PMID- 24722313
TI  - Evaluation of microvascular permeability with dynamic contrast-enhanced MRI for
      the differentiation of primary CNS lymphoma and glioblastoma: radiologic
      pathologic correlation.
AB  - BACKGROUND AND PURPOSE: Dynamic contrast-enhanced MR imaging can provide in vivo
      assessment of the microvasculature in intracranial tumors. The aim of the present
      study was to evaluate the diagnostic performance of dynamic contrast-enhanced MR
      imaging derived vascular permeability parameters, including the volume transfer
      constant, the volume of extravascular extracellular space, and the flux rate
      constant between the extravascular extracellular space and plasma, for the
      differentiation of primary CNS lymphoma and glioblastoma. MATERIALS AND METHODS:
      Sixty glioblastomas and 11 primary central nervous system lymphomas were
      included. Pretreatment T1-weighted dynamic contrast-enhanced MR imaging with a 3D
      T1-weighted spoiled gradient-echo sequence was performed on a 3T MR imaging
      scanner. Perfusion parameters (volume transfer constant, the volume of
      extravascular extracellular space, and the flux rate constant) were measured on
      the basis of the Tofts-Kernmode model. The Mann-Whitney U test and receiver
      operating characteristic analysis were used to compare those parameters between
      primary central nervous system lymphoma and glioblastoma. Histopathologic
      correlation of dynamic contrast-enhanced MR imaging findings was performed by
      using reticulin staining and CD31 immunohistochemistry. RESULTS: Median volume
      transfer constant and flux rate constant values were significantly higher in
      primary central nervous system lymphoma (0.145 +/- 0.057 and 0.396 +/- 0.088)
      than in glioblastoma (0.064 +/- 0.021 and 0.230 +/- 0.058) (P < .001,
      respectively). Median volume of extravascular extracellular space values did not
      differ significantly between primary central nervous system lymphoma (0.434 +/-
      0.165) and glioblastoma (0.319 +/- 0.107). On receiver operating characteristic
      analysis, volume transfer constant had the best discriminative value for
      differentiating primary central nervous system lymphoma and glioblastoma
      (threshold, 0.093; sensitivity, 90.9%; specificity, 95.0%). Histopathologic
      evaluation revealed intact vascular integrity in glioblastoma despite endothelial
      proliferation, whereas primary central nervous system lymphoma demonstrated
      destroyed vessel architecture, thereby promoting vascular disintegrity.
      CONCLUSIONS: Primary central nervous system lymphoma demonstrated significantly
      higher volume transfer constant and flux rate constant values compared with
      glioblastoma, implying a higher vascular permeability in primary central nervous
      system lymphoma. These findings confirm initial observations from perfusion CT
      and dynamic contrast-enhanced MR imaging studies, correlating with underlying
      histopathologic features, and may be useful in distinguishing primary central
      nervous system lymphoma from glioblastoma.

PMID- 24722314
TI  - The thalamus: a small but precious window on tau-related neurodegeneration?

PMID- 24722315
TI  - An interaction between glutathione and the capsid is required for the
      morphogenesis of C-cluster enteroviruses.
AB  - Glutathione (GSH) is the most abundant cellular thiol playing an essential role
      in preserving a reduced cellular environment. Cellular GSH levels can be
      efficiently reduced by the GSH biosynthesis inhibitor, L-buthionine sulfoximine
      (BSO). The aim of our study was to determine the role of GSH in the growth of two
      C-cluster enteroviruses, poliovirus type 1 (PV1) and coxsackievirus A20 (CAV20).
      Our results show that the growth of both PV1 and CAV20 is strongly inhibited by
      BSO and can be partially reversed by the addition of GSH. BSO has no effect on
      viral protein synthesis or RNA replication but it strikingly reduces the
      accumulation of 14S pentamers in infected cells. GSH-pull down assays show that
      GSH directly interacts with capsid precursors and mature virus made in the
      absence of BSO whereas capsid precursors produced under GSH-depletion do not bind
      to GSH. In particular, the loss of binding of GSH may debilitate the stability of
      14S pentamers, resulting in their failure to assemble into mature virus.
      Immunofluorescence cell imaging demonstrated that GSH-depletion did not affect
      the localization of viral capsid proteins to the replication complex. PV1 BSO
      resistant (BSOr) mutants evolved readily during passaging of the virus in the
      presence of BSO. Structural analyses revealed that the BSOr mutations, mapping to
      VP1 and VP3 capsid proteins, are primarily located at protomer/protomer
      interfaces. BSOr mutations might, in place of GSH, aid the stability of 14S
      particles that is required for virion maturation. Our observation that BSOr
      mutants are more heat resistant and need less GSH than wt virus to be protected
      from heat inactivation suggests that they possess a more stable capsid. We
      propose that the role of GSH during enterovirus morphogenesis is to stabilize
      capsid structures by direct interaction with capsid proteins both during and
      after the formation of mature virus particles. 

PMID- 24722316
TI  - Dexamethasone ameliorates H2S-induced acute lung injury by alleviating matrix
      metalloproteinase-2 and -9 expression.
AB  - Acute lung injury (ALI) is one of the fatal outcomes after exposure to high
      levels of hydrogen sulfide (H2S), and the matrix metalloproteinases (MMPs)
      especially MMP-2 and MMP-9 are believed to be involved in the development of ALI
      by degrading the extracellular matrix (ECM) of blood-air barrier. However, the
      roles of MMP-2 and MMP-9 in H2S-induced ALI and the mechanisms of dexamethasone
      (DXM) in treating ALI in clinical practice are still largely unknown. The present
      work was aimed to investigate the roles of MMP-2 and MMP-9 in H2S-induced ALI and
      the protective effects of DXM. In our study, SD rats were exposed to H2S to
      establish the ALI model and in parallel, A549 cells were incubated with NaHS (a
      H2S donor) to establish cell model. The lung HE staining, immunohistochemisty,
      electron microscope assay and wet/dry ratio were used to identify the ALI induced
      by H2S, then the MMP-2 and MMP-9 expression in both rats and A549 cells were
      detected. Our results revealed that MMP-2 and MMP-9 were obviously increased in
      both mRNA and protein level after H2S exposure, and they could be inhibited by
      MMP inhibitor doxycycline (DOX) in rat model. Moreover, DXM significantly
      ameliorated the symptoms of H2S-induced ALI including alveolar edema,
      infiltration of inflammatory cells and the protein leakage in BAFL via up
      regulating glucocorticoid receptor(GR) to mediate the suppression of MMP-2 and
      MMP-9. Furthermore, the protective effects of DXM in vivo and vitro study could
      be partially blocked by co-treated with GR antagonist mifepristone (MIF). Our
      results, taken together, demonstrated that MMP-2 and MMP-9 were involved in the
      development of H2S-induced ALI and DXM exerted protective effects by alleviating
      the expression of MMP-2 and MMP-9. Therefore, MMP-2 and MMP-9 might represent
      novel pharmacological targets for the treatment of H2S and other hazard gases
      induced ALI.

PMID- 24722317
TI  - Lin28a regulates neuronal differentiation and controls miR-9 production.
AB  - microRNAs shape the identity and function of cells by regulating gene expression.
      It is known that brain-specific miR-9 is controlled transcriptionally; however,
      it is unknown whether post-transcriptional processes contribute to establishing
      its levels. Here we show that miR-9 is regulated transcriptionally and post
      transcriptionally during neuronal differentiation of the embryonic carcinoma cell
      line P19. We demonstrate that miR-9 is more efficiently processed in
      differentiated than in undifferentiated cells. We reveal that Lin28a affects miR
      9 by inducing the degradation of its precursor through a uridylation-independent
      mechanism. Furthermore, we show that constitutively expressed untagged but not
      GFP-tagged Lin28a decreases differentiation capacity of P19 cells, which
      coincides with reduced miR-9 levels. Finally, using an inducible system we
      demonstrate that Lin28a can also reduce miR-9 levels in differentiated P19 cells.
      Together, our results shed light on the role of Lin28a in neuronal
      differentiation and increase our understanding of the mechanisms regulating the
      level of brain-specific microRNAs. 

PMID- 24722318
TI  - Usnic acid-loaded biocompatible magnetic PLGA-PVA microsphere thin films
      fabricated by MAPLE with increased resistance to staphylococcal colonization.
AB  - Due to their persistence and resistance to the current therapeutic approaches,
      Staphylococcus aureus biofilm-associated infections represent a major cause of
      morbidity and mortality in the hospital environment. Since (+)-usnic acid (UA), a
      secondary lichen metabolite, possesses antimicrobial activity against Gram
      positive cocci, including S. aureus, the aim of this study was to load magnetic
      polylactic-co-glycolic acid-polyvinyl alcohol (PLGA-PVA) microspheres with UA,
      then to obtain thin coatings using matrix-assisted pulsed laser evaporation and
      to quantitatively assess the capacity of the bio-nano-active modified surface to
      control biofilm formation by S. aureus, using a culture-based assay. The UA
      loaded microspheres inhibited both the initial attachment of S. aureus to the
      coated surfaces, as well as the development of mature biofilms. In vitro
      bioevalution tests performed on the fabricated thin films revealed great
      biocompatibility, which may endorse them as competitive candidates for the
      development of improved non-toxic surfaces resistant to S. aureus colonization
      and as scaffolds for stem cell cultivation and tissue engineering. 

PMID- 24722319
TI  - BEAST 2: a software platform for Bayesian evolutionary analysis.
AB  - We present a new open source, extensible and flexible software platform for
      Bayesian evolutionary analysis called BEAST 2. This software platform is a re
      design of the popular BEAST 1 platform to correct structural deficiencies that
      became evident as the BEAST 1 software evolved. Key among those deficiencies was
      the lack of post-deployment extensibility. BEAST 2 now has a fully developed
      package management system that allows third party developers to write additional
      functionality that can be directly installed to the BEAST 2 analysis platform via
      a package manager without requiring a new software release of the platform. This
      package architecture is showcased with a number of recently published new models
      encompassing birth-death-sampling tree priors, phylodynamics and model averaging
      for substitution models and site partitioning. A second major improvement is the
      ability to read/write the entire state of the MCMC chain to/from disk allowing it
      to be easily shared between multiple instances of the BEAST software. This
      facilitates checkpointing and better support for multi-processor and high-end
      computing extensions. Finally, the functionality in new packages can be easily
      added to the user interface (BEAUti 2) by a simple XML template-based mechanism
      because BEAST 2 has been re-designed to provide greater integration between the
      analysis engine and the user interface so that, for example BEAST and BEAUti use
      exactly the same XML file format. 

PMID- 24722320
TI  - Non-integrating gamma-retroviral vectors as a versatile tool for transient zinc
      finger nuclease delivery.
AB  - Designer nucleases, like zinc-finger nucleases (ZFNs), represent valuable tools
      for targeted genome editing. Here, we took advantage of the gamma-retroviral life
      cycle and produced vectors to transfer ZFNs in the form of protein, mRNA and
      episomal DNA. Transfer efficacy and ZFN activity were assessed in quantitative
      proof-of-concept experiments in a human cell line and in mouse embryonic stem
      cells. We demonstrate that retrovirus-mediated protein transfer (RPT), retrovirus
      mediated mRNA transfer (RMT), and retrovirus-mediated episome transfer (RET)
      represent powerful methodologies for transient protein delivery or protein
      expression. Furthermore, we describe complementary strategies to augment ZFN
      activity after gamma-retroviral transduction, including serial transduction,
      proteasome inhibition, and hypothermia. Depending on vector dose and target cell
      type, gene disruption frequencies of up to 15% were achieved with RPT and RMT,
      and >50% gene knockout after RET. In summary, non-integrating gamma-retroviral
      vectors represent a versatile tool to transiently deliver ZFNs to human and mouse
      cells. 

PMID- 24722321
TI  - Epigenetics in comparative biology: why we should pay attention.
AB  - The past decade has seen an explosion of articles in scientific journals
      involving non-genetic influences on phenotype through modulation of gene function
      without changes in gene sequence. The excitement in modern molecular biology
      surrounding the impact exerted by the environment on development of the phenotype
      is focused largely on mechanism and has not incorporated questions asked (and
      answers provided) by early philosophers, biologists, and psychologists. As such,
      this emergence of epigenetic studies is somewhat "old wine in new bottles" and
      represents a reformulation of the old debate of preformationism versus epigenesis
      one resolved in the 1800s. Indeed, this tendency to always look forward, with
      minimal concern or regard of what has gone before, has led to the present
      situation in which "true" epigenetic studies are believed to consist of one of
      two schools. The first is primarily medically based and views epigenetic
      mechanisms as pathways for disease (e.g., "the epigenetics of cancer"). The
      second is primarily from the basic sciences, particularly molecular genetics, and
      regards epigenetics as a potentially important mechanism for organisms exposed to
      variable environments across multiple generations. There is, however, a third,
      and separate, school based on the historical literature and debates and regards
      epigenetics as more of a perspective than a phenomenon. Against this backdrop,
      comparative integrative biologists are particularly well-suited to understand
      epigenetic phenomena as a way for organisms to respond rapidly with modified
      phenotypes (relative to natural selection) to changes in the environment. Using
      evolutionary principles, it is also possible to interpret "sunsetting" of
      modified phenotypes when environmental conditions result in a disappearance of
      the epigenetic modification of gene regulation. Comparative integrative
      biologists also recognize epigenetics as a potentially confounding source of
      variation in their data. Epigenetic modification of phenotype (molecular,
      cellular, morphological, physiological, and behavioral) can be highly variable
      depending upon ancestral environmental exposure and can contribute to apparent
      "random" noise in collected datasets. Thus, future research should go beyond the
      study of epigenetic mechanisms at the level of the gene and devote additional
      investigation of epigenetic outcomes at the level of both the individual organism
      and how it affects the evolution of populations. This review is the first of
      seven in this special issue of Integrative and Comparative Biology that addresses
      in detail these and other key topics in the study of epigenetics. 

PMID- 24722322
TI  - Respirophasic carotid artery peak velocity variation as a predictor of fluid
      responsiveness in mechanically ventilated patients with coronary artery disease.
AB  - BACKGROUND: We studied respirophasic variation in carotid artery blood flow peak
      velocity (DeltaVpeak-CA) measured by pulsed wave Doppler ultrasound as a
      predictor of fluid responsiveness in mechanically ventilated patients with
      coronary artery disease. METHODS: Forty patients undergoing elective coronary
      artery bypass surgery were enrolled. Subjects were classified as responders if
      stroke volume index (SVI) increased >=15% after volume expansion (6 ml kg(-1)).
      The DeltaVpeak-CA was calculated as the difference between the maximum and
      minimum values of peak velocity over a single respiratory cycle, divided by the
      average. Central venous pressure, pulmonary artery occlusion pressure, pulse
      pressure variation (PPV), and DeltaVpeak-CA were recorded before and after volume
      expansion. RESULTS: PPV and DeltaVpeak-CA correlated significantly with an
      increase in SVI after volume expansion. Area under the receiver-operator
      characteristic curve (AUROC) of PPV and DeltaVpeak-CA were 0.75 [95% confidence
      interval (CI) 0.59-0.90] and 0.85 (95% CI 0.72-0.97). The optimal cut-off values
      for fluid responsiveness of PPV and DeltaVpeak-CA were 13% (sensitivity and
      specificity of 0.74 and 0.71) and 11% (sensitivity and specificity of 0.85 and
      0.82), respectively. In a subgroup analysis of 17 subjects having pulse pressure
      hypertension (>= 60 mm Hg), PPV failed to predict fluid responsiveness (AUROC
      0.70, P=0.163), whereas the predictability of DeltaVpeak-CA remained unchanged
      (AUROC 0.90, P=0.006). CONCLUSIONS: Doppler assessment of respirophasic
      DeltaVpeak-CA seems to be a highly feasible and reliable method to predict fluid
      responsiveness in mechanically ventilated patients undergoing coronary
      revascularization. CLINICAL TRIAL REGISTRATION: NCT 01836081.

PMID- 24722323
TI  - Quality assessment of TPB-based questionnaires: a systematic review.
AB  - OBJECTIVE: This review is aimed at assessing the quality of questionnaires and
      their development process based on the theory of planned behavior (TPB) change
      model. METHODS: A systematic literature search for studies with the primary aim
      of TPB-based questionnaire development was conducted in relevant databases
      between 2002 and 2012 using selected search terms. Ten of 1,034 screened
      abstracts met the inclusion criteria and were assessed for methodological quality
      using two different appraisal tools: one for the overall methodological quality
      of each study and the other developed for the appraisal of the questionnaire
      content and development process. Both appraisal tools consisted of items
      regarding the likelihood of bias in each study and were eventually combined to
      give the overall quality score for each included study. RESULTS: 8 of the 10
      included studies showed low risk of bias in the overall quality assessment of
      each study, while 9 of the studies were of high quality based on the quality
      appraisal of questionnaire content and development process. CONCLUSION: Quality
      appraisal of the questionnaires in the 10 reviewed studies was successfully
      conducted, highlighting the top problem areas (including: sample size estimation;
      inclusion of direct and indirect measures; and inclusion of questions on
      demographics) in the development of TPB-based questionnaires and the need for
      researchers to provide a more detailed account of their development process.

PMID- 24722324
TI  - Current developments in understanding of West Nile virus central nervous system
      disease.
AB  - PURPOSE OF REVIEW: West Nile virus (WNV) is the most important cause of epidemic
      encephalitis in the United States. We review articles published in the last 18
      months related to the epidemiology, immunology, clinical features, and treatment
      of this disease. RECENT FINDINGS: There was a resurgence in WNV disease in the
      United States in 2012. The WNV strain now predominant in the United States
      (NA/WN02) differs from the initial emergent isolate in 1999 (NY99). However,
      differences in the genetics of currently circulating United States WNV strains do
      not explain variations in epidemic magnitude or disease severity. Innate and
      acquired immunity are critical in control of WNV, and in some cases pathways are
      central nervous system specific. The clinical features of infection are now well
      understood, although nonconfirmed observations of chronic viral excretion in
      urine remain controversial. There is no specific antiviral therapy for WNV, but
      studies of antivirals specific for other flaviviruses may identify agents with
      promise against WNV. Phase I and II human WNV vaccine clinical trials have
      established that well tolerated and immunogenic WNV vaccines can be developed.
      SUMMARY: WNV remains an important public health problem. Although recent studies
      have significantly increased our understanding of host immune and genetic factors
      involved in control of WNV infection, no specific therapy is yet available.
      Development of a well tolerated, immunogenic, and effective vaccine against WNV
      is almost certainly feasible, but economic factors and the lack of predictability
      of the magnitude and location of outbreaks are problematic for designing phase
      III trials and ultimate licensure.

PMID- 24722327
TI  - Novel rearrangements in the staphylococcal cassette chromosome mec type V
      elements of Indian ST772 and ST672 methicillin resistant Staphylococcus aureus
      strains.
AB  - Staphylococcus aureus is a commensal gram positive bacteria which causes severe
      and non severe infections in humans and livestock. In India, ST772 is a dominant
      and ST672 is an emerging clone of Staphylococcus aureus. Both cause serious human
      diseases, and carry type V SCCmec elements. The objective of this study was to
      characterize SCCmec type V elements of ST772 and ST672 because the usual PCR
      methods did not amplify all primers specific to the type. Whole genome sequencing
      analysis of seven ST772 and one ST672 S. aureus isolates revealed that the SCCmec
      elements of six of the ST772 isolates were the smallest of the extant type V
      elements and in addition have several other novel features. Only one ST772
      isolate and the ST672 isolate carried bigger SCCmec cassettes which were
      composites carrying multiple ccrC genes. These cassettes had some similarities to
      type V SCCmec element from M013 isolate (ST59) from Taiwan in certain aspects.
      SCCmec elements of all Indian isolates had an inversion of the mec complex,
      similar to the bovine SCCmec type X. This study reveals that six out of seven
      ST772 S. aureus isolates have a novel type V (5C2) SCCmec element while one each
      of ST772 and ST672 isolates have a composite SCCmec type V element (5C2&5) formed
      by the integration of type V SCCmec into a MSSA carrying a SCC element, in
      addition to the mec gene complex inversions and extensive recombinations. 

PMID- 24722325
TI  - Relapsing and progressive forms of multiple sclerosis: insights from pathology.
AB  - PURPOSE OF REVIEW: The predominant clinical disease course of multiple sclerosis
      starts with reversible episodes of neurological disability, which transforms into
      progressive neurological decline. This review provides insight into the
      pathological differences during relapsing and progressive phases of multiple
      sclerosis. RECENT FINDINGS: The clinical course of multiple sclerosis is
      variable, and the disease can be classified into relapsing and progressive
      phases. Pathological studies have been successful in distinguishing between these
      two forms of the disease and correlate with the clinical findings in terms of
      cellular responses, the inflammatory environment, and the location of lesions.
      SUMMARY: Available therapies for multiple sclerosis patients, while effective
      during the relapsing phase, have little benefit for progressive multiple
      sclerosis patients. Development of therapies to benefit progressive multiple
      sclerosis patients will require a better understanding of the pathogenesis of
      progressive multiple sclerosis. This review discusses and compares the
      pathological findings in relapsing and progressive multiple sclerosis patients.

PMID- 24722328
TI  - Automatic localization of the left ventricle from cardiac cine magnetic resonance
      imaging: a new spectrum-based computer-aided tool.
AB  - Traditionally, cardiac image analysis is done manually. Automatic image
      processing can help with the repetitive tasks, and also deal with huge amounts of
      data, a task which would be humanly tedious. This study aims to develop a
      spectrum-based computer-aided tool to locate the left ventricle using images
      obtained via cardiac magnetic resonance imaging. Discrete Fourier Transform was
      conducted pixelwise on the image sequence. Harmonic images of all frequencies
      were analyzed visually and quantitatively to determine different patterns of the
      left and right ventricles on spectrum. The first and fifth harmonic images were
      selected to perform an anisotropic weighted circle Hough detection. This tool was
      then tested in ten volunteers. Our tool was able to locate the left ventricle in
      all cases and had a significantly higher cropping ratio of 0.165 than did earlier
      studies. In conclusion, a new spectrum-based computer aided tool has been
      proposed and developed for automatic left ventricle localization. The development
      of this technique, which will enable the automatic location and further
      segmentation of the left ventricle, will have a significant impact in research
      and in diagnostic settings. We envisage that this automated method could be used
      by radiographers and cardiologists to diagnose and assess ventricular function in
      patients with diverse heart diseases. 

PMID- 24722329
TI  - Self-esteem in hearing-impaired children: the influence of communication,
      education, and audiological characteristics.
AB  - OBJECTIVE: Sufficient self-esteem is extremely important for psychosocial
      functioning. It is hypothesized that hearing-impaired (HI) children have lower
      levels of self-esteem, because, among other things, they frequently experience
      lower language and communication skills. Therefore, the aim of this study was to
      compare HI children's self-esteem across different domains with those of normal
      hearing (NH) children and to investigate the influence of communication, type of
      education, and audiological characteristics. METHODS: This large (N = 252)
      retrospective, multicenter study consisted of two age- and gender-matched groups:
      123 HI children and 129 NH controls (mean age  = 11.8 years). Self-reports were
      used to measure self-esteem across four domains: perceived social acceptance by
      peers, perceived parental attention, perceived physical appearance, and global
      self-esteem. RESULTS: HI children experienced lower levels of self-esteem
      regarding peers and parents than NH controls. Particularly HI children who
      attended special education for the deaf were at risk, even after correcting for
      their language development and intelligence. Yet, levels of global self-esteem
      and self-esteem involving physical appearance in HI children equalled those of NH
      controls. Furthermore, younger age at implantation and longer duration of having
      cochlear implants (CIs) were related to higher levels of self-esteem. CONCLUSION:
      HI children experience lower levels of self-esteem in the social domains. Yet,
      due to the heterogeneity of the HI population, there is high variability in
      levels of self-esteem. DISCUSSION: Clinicians must always be aware of the risk
      and protective factors related to self-esteem in order to help individual
      patients reach their full potential.

PMID- 24722330
TI  - Overexpression of CCN3 inhibits inflammation and progression of atherosclerosis
      in apolipoprotein E-deficient mice.
AB  - BACKGROUND: Cysteine-rich 61/connective tissue growth factor/nephroblastoma
      overexpressed (CCN) 3 has been recently reported to play a role in regulating
      inflammation of vascular endothelial cells. However, the role of CCN3 in
      atherosclerosis, which is characterized by vascular inflammation, remains
      unclear. HYPOTHESIS AND OBJECTIVES: Overexpression of CCN3 may relieve the
      inflammation response in and inhibit the progress of atherosclerosis. We aimed to
      explore the potential roles of CCN3 in inflammation in atherosclerosis. STRATEGY
      AND MAIN RESULTS: In in vitro studies using cultured human aortic endothelial
      cells and human umbilical vein endothelial cells, CCN3 mRNA and protein
      expression significantly decreased in response to tumor necrosis factor-alpha and
      interleukin-1beta treatments (p<0.05), when analyzed by quantitative real-time
      polymerase chain reaction and Western blot. Using a mouse model of
      atherosclerosis, the mRNA and protein levels of CCN3 decreased by 72.2% (p =
      0.041) and 86.4% (p = 0.036), respectively, compared with levels in wild-type
      control mice, respectively. Overexpression of CCN3 by adenovirus-mediated gene
      overexpression decreased low-density lipoprotein cholesterol by 48.9% (p =
      0.017), total cholesterol by 58.9% (p = 0.031), and triglycerides by 56.8% (p =
      0.022), and it increased high-density lipoprotein cholesterol level by 2.16-fold
      (p = 0.039), compared with control groups. Additionally, a reduced plaque area
      and increased fibrous cap were observed (p<0.05). Furthermore, CCN3
      overexpression decreased cell adhesion molecule-1 mRNA expression by 84.7% (p =
      0.007) and intercellular adhesion molecule-1 mRNA expression by 61.2% (p =
      0.044). Inflammatory factors, including matrix metalloproteinases, cyclooxygenase
      2, and tissue factor also significantly (p<0.05) decreased with CCN3
      overexpression in the atherosclerotic mouse model. Additionally, CCN1 and CCN2,
      which have been reported to be highly expressed in aortic atherosclerotic
      plaques, were significantly downregulated (p<0.05) by CCN3 overexpression.
      CONCLUSION: CCN3 overexpression is associated with control of inflammatory
      processes and reversion of dyslipidemia in the process of atherosclerosis, which
      implies that CCN3 may be a promising target in the treatment of atherosclerosis.

PMID- 24722331
TI  - Steroid receptor RNA activator (SRA) modification by the human pseudouridine
      synthase 1 (hPus1p): RNA binding, activity, and atomic model.
AB  - The most abundant of the modified nucleosides, and once considered as the "fifth"
      nucleotide in RNA, is pseudouridine, which results from the action of
      pseudouridine synthases. Recently, the mammalian pseudouridine synthase 1
      (hPus1p) has been reported to modulate class I and class II nuclear receptor
      responses through its ability to modify the Steroid receptor RNA Activator (SRA).
      These findings highlight a new level of regulation in nuclear receptor (NR)
      mediated transcriptional responses. We have characterised the RNA association and
      activity of the human Pus1p enzyme with its unusual SRA substrate. We validate
      that the minimal RNA fragment within SRA, named H7, is necessary for both the
      association and modification by hPus1p. Furthermore, we have determined the
      crystal structure of the catalytic domain of hPus1p at 2.0 A resolution, alone
      and in a complex with several molecules present during crystallisation. This
      model shows an extended C-terminal helix specifically found in the eukaryotic
      protein, which may prevent the enzyme from forming a homodimer, both in the
      crystal lattice and in solution. Our biochemical and structural data help to
      understand the hPus1p active site architecture, and detail its particular
      requirements with regard to one of its nuclear substrates, the non-coding RNA
      SRA.

PMID- 24722332
TI  - Caspase-1-like regulation of the proPO-system and role of ppA and caspase-1-like
      cleaved peptides from proPO in innate immunity.
AB  - Invertebrates rely on innate immunity to respond to the entry of foreign
      microorganisms. One of the important innate immune responses in arthropods is the
      activation of prophenoloxidase (proPO) by a proteolytic cascade finalized by the
      proPO-activating enzyme (ppA), which leads to melanization and the elimination of
      pathogens. Proteolytic cascades play a crucial role in innate immune reactions
      because they can be triggered more quickly than immune responses that require
      altered gene expression. Caspases are intracellular proteases involved in tightly
      regulated limited proteolysis of downstream processes and are also involved in
      inflammatory responses to infections for example by activation of interleukin
      1beta. Here we show for the first time a link between caspase cleavage of proPO
      and release of this protein and the biological function of these fragments in
      response to bacterial infection in crayfish. Different fragments from the
      cleavage of proPO were studied to determine their roles in bacterial clearance
      and antimicrobial activity. These fragments include proPO-ppA, the N-terminal
      part of proPO cleaved by ppA, and proPO-casp1 and proPO-casp2, the fragments from
      the N-terminus after cleavage by caspase-1. The recombinant proteins
      corresponding to all three of these peptide fragments exhibited bacterial
      clearance activity in vivo, and proPO-ppA had antimicrobial activity, as
      evidenced by a drastic decrease in the number of Escherichia coli in vitro. The
      bacteria incubated with the proPO-ppA fragment were agglutinated and their cell
      morphology was altered. Our findings show an evolutionary conserved role for
      caspase cleavage in inflammation, and for the first time show a link between
      caspase induced inflammation and melanization. Further we give a more detailed
      understanding of how the proPO system is regulated in time and place and a role
      for the peptide generated by activation of proPO as well as for the peptides
      resulting from Caspase 1 proteolysis. 

PMID- 24722333
TI  - Multiple model-informed open-loop control of uncertain intracellular signaling
      dynamics.
AB  - Computational approaches to tune the activation of intracellular signal
      transduction pathways both predictably and selectively will enable researchers to
      explore and interrogate cell biology with unprecedented precision. Techniques to
      control complex nonlinear systems typically involve the application of control
      theory to a descriptive mathematical model. For cellular processes, however,
      measurement assays tend to be too time consuming for real-time feedback control
      and models offer rough approximations of the biological reality, thus limiting
      their utility when considered in isolation. We overcome these problems by
      combining nonlinear model predictive control with a novel adaptive weighting
      algorithm that blends predictions from multiple models to derive a compromise
      open-loop control sequence. The proposed strategy uses weight maps to inform the
      controller of the tendency for models to differ in their ability to accurately
      reproduce the system dynamics under different experimental perturbations (i.e.
      control inputs). These maps, which characterize the changing model likelihoods
      over the admissible control input space, are constructed using preexisting
      experimental data and used to produce a model-based open-loop control framework.
      In effect, the proposed method designs a sequence of control inputs that force
      the signaling dynamics along a predefined temporal response without measurement
      feedback while mitigating the effects of model uncertainty. We demonstrate this
      technique on the well-known Erk/MAPK signaling pathway in T cells. In silico
      assessment demonstrates that this approach successfully reduces target tracking
      error by 52% or better when compared with single model-based controllers and non
      adaptive multiple model-based controllers. In vitro implementation of the
      proposed approach in Jurkat cells confirms a 63% reduction in tracking error when
      compared with the best of the single-model controllers. This study provides an
      experimentally-corroborated control methodology that utilizes the knowledge
      encoded within multiple mathematical models of intracellular signaling to design
      control inputs that effectively direct cell behavior in open-loop. 

PMID- 24722334
TI  - Muscle MR imaging in tubular aggregate myopathy.
AB  - PURPOSE: To evaluate with Magnetic Resonance (MR) the degree of fatty replacement
      and edematous involvement in skeletal muscles in patients with Tubular Aggregate
      Myopathy (TAM). To asses the inter-observer agreement in evaluating muscle
      involvement and the symmetry index of fatty replacement. MATERIALS AND METHODS:
      13 patients were evaluated by MR to ascertain the degree of fatty replacement
      (T1W sequences) according to Mercuri's scale, and edema score (STIR sequences)
      according to extent and site. RESULTS: Fatty replacement mainly affects the
      posterior superficial compartment of the leg; the anterior compartment is
      generally spared. Edema was generally poor and almost only in the superficial
      compartment of the leg. The inter-observer agreement is very good with a
      Krippendorff's coefficient >0.9. Data show a total symmetry in the muscular
      replacement (McNemar-Bowker test with p = 1). CONCLUSIONS: MR reveals
      characteristic muscular involvement, and is a reproducible technique for
      evaluation of TAM. There may also be a characteristic involvement of the long and
      short heads of the biceps femoris. It is useful for aimed biopsies, diagnostic
      hypotheses and evaluation of disease progression.

PMID- 24722335
TI  - Water, Sanitation, and Hygiene (WASH): a critical component for sustainable soil
      transmitted helminth and schistosomiasis control.

PMID- 24722336
TI  - Association of plasma IL-6 and Hsp70 with HRV at different levels of PAHs
      metabolites.
AB  - BACKGROUND: Exposure to polycyclic aromatic hydrocarbons (PAHs) is associated
      with reduced heart rate variability (HRV), a strong predictor of cardiovascular
      diseases, but the mechanism is not well understood. OBJECTIVES: We hypothesized
      that PAHs might induce systemic inflammation and stress response, contributing to
      altered cardiac autonomic function. METHODS: HRV indices were measured using a 3
      channel digital Holter monitor in 800 coke oven workers. Plasma levels of
      interleukin-6 (IL-6) and heat shock protein 70 (Hsp70) were determined using
      ELISA. Twelve urinary PAHs metabolites (OH-PAHs) were measured by gas
      chromatography-mass spectrometry. RESULTS: We found that significant dose
      dependent relationships between four urinary OH-PAHs and IL-6 (all Ptrend<0.05);
      and an increase in quartiles of IL-6 was significantly associated with a decrease
      in total power (TP) and low frequency (LF) (Ptrend = 0.014 and 0.006,
      respectively). In particular, elevated IL-6 was associated in a dose-dependent
      manner with decreased TP and LF in the high-PAHs metabolites groups (all
      Ptrend<0.05), but not in the low-PAHs metabolites groups. No significant
      association between Hsp70 and HRV in total population was found after
      multivariate adjustment. However, increased Hsp70 was significantly associated
      with elevated standard deviation of NN intervals (SDNN), TP and LF in the low
      PAHs metabolites groups (all Ptrend<0.05). We also observed that both IL-6 and
      Hsp70 significantly interacted with multiple PAHs metabolites in relation to HRV.
      CONCLUSIONS: In coke oven workers, increased IL-6 was associated with a dose
      response decreased HRV in the high-PAHs metabolites groups, whereas increase of
      Hsp70 can result in significant dose-related increase in HRV in the low-PAHs
      metabolites groups.

PMID- 24722337
TI  - The first observation of memory effects in the infrared (FT-IR) measurements: do
      successive measurements remember each other?
AB  - Over the past couple of decades there have been major advances in the field of
      nanoscience and nanotechnology. Many applications have sprouted from these fields
      of research. It is essential, given the scale of the materials, to attain
      accurate, valid and reproducible measurements. Material properties have shown to
      be a function of their size and composition. Physiochemical properties of the
      nanomaterials can significantly alter material behavior compared to bulk
      counterparts. For example, metal oxide nanoparticles have found broad
      applications ranging from photo-catalysis to antibacterial agents. In our study,
      we synthesized CuO nanoparticles using well established sol-gel based methods
      with varying levels of Ni doping. However, upon analysis of measured infrared
      data, we discovered the presence of quasi-periodic (QP) processes. Such processes
      have previously been reported to be tightly associated with measurement memory
      effects. We were able to detect the desired QP process in these measurements from
      three highly accurate repetitive experiments performed on each Ni (1-7%) doped
      CuO sample. In other words, successive measurements performed in a rather short
      period of time remember each other at least inside a group of neighboring
      measurements. 

PMID- 24722338
TI  - The transcription factor Egr3 is a putative component of the microtubule
      organizing center in mouse oocytes.
AB  - The early growth response (Egr) family of zinc finger transcription factors
      consists of 4 members. During an investigation of Egr factor localization in
      mouse ovaries, we noted that Egr3 exhibits a subcellular localization that
      overlaps with the meiotic spindle in oocytes. Using Egr3-specific antibodies, we
      establish that Egr3 co-localizes with the spindle and cytosolic microtubule
      organizing centers (MTOCs) in oocytes during meiotic maturation. Notably, the
      Egr3 protein appears to accumulate around gamma-tubulin in MTOCs. Nocodazole
      treatment, which induces microtubule depolymerization, resulted in the disruption
      of spindle formation and Egr3 localization, suggesting that Egr3 localization is
      dependent on the correct configuration of the spindle. Shortly after warming of
      vitrified oocytes, growing arrays of microtubules were observed near large
      clusters of Egr3. An in vitro microtubule interaction assay showed that Egr3 does
      not directly interact with polymerized microtubules. Egr3 localization on the
      spindle was sustained in early preimplantation mouse embryos, but this pattern
      did not persist until the blastocyst stage. Collectively, our result shows for
      the first time that the Egr3 a transcription factor may play a novel non
      transcriptional function during microtubule organization in mouse oocytes.

PMID- 24722339
TI  - Histone deacetylase 1 and p300 can directly associate with chromatin and compete
      for binding in a mutually exclusive manner.
AB  - Lysine acetyltransferases (KATs) and histone deacetylases (HDACs) are important
      epigenetic modifiers and dynamically cycled on active gene promoters to regulate
      transcription. Although HDACs are recruited to gene promoters and DNA
      hypersensitive sites through interactions with DNA binding factors, HDAC
      activities are also found globally in intergenic regions where DNA binding
      factors are not present. It is suggested that HDACs are recruited to those
      regions through other distinct, yet undefined mechanisms. Here we show that HDACs
      can be directly recruited to chromatin in the absence of other factors through
      direct interactions with both DNA and core histone subunits. HDACs interact with
      DNA in a non-sequence specific manner. HDAC1 and p300 directly bind to the
      overlapping regions of the histone H3 tail and compete for histone binding.
      Previously we show that p300 can acetylate HDAC1 to attenuate deacetylase
      activity. Here we have further mapped two distinct regions of HDAC1 that interact
      with p300. Interestingly, these regions of HDAC1 also associate with histone H3.
      More importantly, p300 and HDAC1 compete for chromatin binding both in vitro and
      in vivo. Therefore, the mutually exclusive associations of HDAC1/p300,
      p300/histone, and HDAC1/histone on chromatin contribute to the dynamic regulation
      of histone acetylation by balancing HDAC or KAT activity present at histones to
      reorganize chromatin structure and regulate transcription. 

PMID- 24722340
TI  - Location of dual sites in E. coli FtsZ important for degradation by ClpXP; one at
      the C-terminus and one in the disordered linker.
AB  - ClpXP is a two-component ATP-dependent protease that unfolds and degrades
      proteins bearing specific recognition signals. One substrate degraded by
      Escherichia coli ClpXP is FtsZ, an essential cell division protein. FtsZ forms
      polymers that assemble into a large ring-like structure, termed the Z-ring,
      during cell division at the site of constriction. The FtsZ monomer is composed of
      an N-terminal polymerization domain, an unstructured linker region and a C
      terminal conserved region. To better understand substrate selection by ClpXP, we
      engineered FtsZ mutant proteins containing amino acid substitutions or deletions
      near the FtsZ C-terminus. We identified two discrete regions of FtsZ important
      for degradation of both FtsZ monomers and polymers by ClpXP in vitro. One region
      is located 30 residues away from the C-terminus in the unstructured linker region
      that connects the polymerization domain to the C-terminal region. The other
      region is near the FtsZ C-terminus and partially overlaps the recognition sites
      for several other FtsZ-interacting proteins, including MinC, ZipA and FtsA.
      Mutation of either region caused the protein to be more stable and mutation of
      both caused an additive effect, suggesting that both regions are important. We
      also observed that in vitro MinC inhibits degradation of FtsZ by ClpXP,
      suggesting that some of the same residues in the C-terminal site that are
      important for degradation by ClpXP are important for binding MinC.

PMID- 24722341
TI  - Elimination of ligation dependent artifacts in T4 RNA ligase to achieve high
      efficiency and low bias microRNA capture.
AB  - Adapter ligation is a critical first step in many microRNA analysis methods
      including microarray, qPCR, and sequencing. Previous studies have shown that
      ligation bias can have dramatic effects on both the fidelity of expression
      profiles and reproducibility across samples. We have developed a method for high
      efficiency and low bias microRNA capture by 3' adapter ligation using T4 RNA
      ligase that does not require pooled adapters. Using a panel of 20 microRNA, we
      investigated the effects of ligase type, PEG concentration, ligase amount,
      adapter concentration, incubation time, incubation temperature, and adapter
      design on capture efficiency and bias. Of these factors, high PEG% was found to
      be critical in suppressing ligation bias. We obtained high average capture
      efficiency and low CV across the 20 microRNA panel, both in idealized buffer
      conditions (86% +/- 10%) and total RNA spiking conditions (64% +/- 17%). We
      demonstrate that this method is reliable across microRNA species that previous
      studies have had difficulty capturing and that our adapter design performs
      significantly better than the common adapter designs. Further, we demonstrate
      that the optimization methodology must be specifically designed for minimizing
      bias in order to obtain the ideal reaction parameters.

PMID- 24722343
TI  - Electronic data capture tools for global health programs: evolution of LINKS, an
      Android-, web-based system.

PMID- 24722342
TI  - 6-methoxyflavanones as bitter taste receptor blockers for hTAS2R39.
AB  - Many (dietary) bitter compounds, e.g. flavonoids, activate bitter receptor
      hTAS2R39 in cell-based assays. Several flavonoids, amongst which some flavanones,
      are known not to activate this receptor. As certain flavanones are known to mask
      bitter taste sensorially, flavanones might act as bitter receptor antagonists.
      Fourteen flavanones were investigated for their potential to reduce activation of
      hTAS2R39 by epicatechin gallate (ECG), one of the main bitter compounds occurring
      in green tea. Three flavanones showed inhibitory behavior towards the activation
      of hTAS2R39 by ECG: 4'-fluoro-6-methoxyflavanone, 6,3'-dimethoxyflavanone, and 6
      methoxyflavanone (in order of decreasing potency). The 6-methoxyflavanones also
      inhibited activation of hTAS2R14 (another bitter receptor activated by ECG),
      though to a lesser extent. Dose-response curves of ECG at various concentrations
      of the full antagonist 4'-fluoro-6-methoxyflavanone and wash-out experiments
      indicated reversible insurmountable antagonism. The same effect was observed for
      the structurally different agonist denatonium benzoate. 

PMID- 24722344
TI  - The sun, moon, wind, and biological imperative-shaping contrasting wintertime
      migration and foraging strategies of adult male and female northern fur seals
      (Callorhinus ursinus).
AB  - Adult male and female northern fur seals (Callorhinus ursinus) are sexually
      segregated in different regions of the North Pacific Ocean and Bering Sea during
      their winter migration. Explanations for this involve interplay between
      physiology, predator-prey dynamics, and ecosystem characteristics, however
      possible mechanisms lack empirical support. To investigate factors influencing
      the winter ecology of both sexes, we deployed five satellite-linked conductivity,
      temperature, and depth data loggers on adult males, and six satellite-linked
      depth data loggers and four satellite transmitters on adult females from St. Paul
      Island (Bering Sea, Alaska, USA) in October 2009. Males and females migrated to
      different regions of the North Pacific Ocean: males wintered in the Bering Sea
      and northern North Pacific Ocean, while females migrated to the Gulf of Alaska
      and California Current. Horizontal and vertical movement behaviors of both sexes
      were influenced by wind speed, season, light (sun and moon), and the ecosystem
      they occupied, although the expression of the behaviors differed between sexes.
      Male dive depths were aligned with the depth of the mixed layer during daylight
      periods and we suspect this was the case for females upon their arrival to the
      California Current. We suggest that females, because of their smaller size and
      physiological limitations, must avoid severe winters typical of the northern
      North Pacific Ocean and Bering Sea and migrate long distances to areas of more
      benign environmental conditions and where prey is shallower and more accessible.
      In contrast, males can better tolerate often extreme winter ocean conditions and
      exploit prey at depth because of their greater size and physiological
      capabilities. We believe these contrasting winter behaviors 1) are a consequence
      of evolutionary selection for large size in males, important to the acquisition
      and defense of territories against rivals during the breeding season, and 2) ease
      environmental/physiological constraints imposed on smaller females. 

PMID- 24722345
TI  - First experience with a new miniaturized pump-driven venovenous extracorporeal
      CO2 removal system (iLA Activve): a retrospective data analysis.
AB  - iLA Activve is a new minimally invasive device for extracorporeal CO2 removal
      (ECCO2-R) using a miniaturized pump, a special gas exchange membrane, and a
      double-lumen cannula. We retrospectively analyzed our experiences in 12 patients
      with hypercapnic respiratory failure undergoing ECCO2-R. Indication for ECCO2-R
      was hypercapnia due to terminal lung failure during bridging to lung
      transplantation, pneumonia, and chronic obstructive lung disease or asthma. The
      median duration of ECCO2-R was 8 days (range 2-30). Seven patients were
      successfully weaned and five died. Patients with primarily hypoxic lung failure
      were significantly longer ventilated before ECCO2-R and had a higher mortality
      rate. Complications were retroperitoneal hematoma after cannulation in one
      patient and repeated system changes because of clotting in two patients. We
      observed effective CO2 removal in all patients, with significant reduction in
      ventilation pressures and minute volumes at median blood flow rates of 1.2-1.4
      L/min. The iLA Activve system using venous double-lumen cannulas proved to be an
      effective method for ECCO2-R. Invasiveness of ventilation could be reduced.
      Additional severe impairment of oxygenation and prolonged mechanical ventilation
      before ECCO2-R are factors of adverse prognosis. The use of ECCO2-R should be
      thoroughly reconsidered in these cases. 

PMID- 24722346
TI  - The evolution of multivariate maternal effects.
AB  - There is a growing interest in predicting the social and ecological contexts that
      favor the evolution of maternal effects. Most predictions focus, however, on
      maternal effects that affect only a single character, whereas the evolution of
      maternal effects is poorly understood in the presence of suites of interacting
      traits. To overcome this, we simulate the evolution of multivariate maternal
      effects (captured by the matrix M) in a fluctuating environment. We find that the
      rate of environmental fluctuations has a substantial effect on the properties of
      M: in slowly changing environments, offspring are selected to have a multivariate
      phenotype roughly similar to the maternal phenotype, so that M is characterized
      by positive dominant eigenvalues; by contrast, rapidly changing environments
      favor Ms with dominant eigenvalues that are negative, as offspring favor a
      phenotype which substantially differs from the maternal phenotype. Moreover, when
      fluctuating selection on one maternal character is temporally delayed relative to
      selection on other traits, we find a striking pattern of cross-trait maternal
      effects in which maternal characters influence not only the same character in
      offspring, but also other offspring characters. Additionally, when selection on
      one character contains more stochastic noise relative to selection on other
      traits, large cross-trait maternal effects evolve from those maternal traits that
      experience the smallest amounts of noise. The presence of these cross-trait
      maternal effects shows that individual maternal effects cannot be studied in
      isolation, and that their study in a multivariate context may provide important
      insights about the nature of past selection. Our results call for more studies
      that measure multivariate maternal effects in wild populations. 

PMID- 24722347
TI  - Hyaluronic acid-modified magnetic iron oxide nanoparticles for MR imaging of
      surgically induced endometriosis model in rats.
AB  - Endometriosis is defined as the presence of endometrial tissue outside the
      uterine, which may affect nearly 60% of women in reproductive age. Deep
      infiltrating endometriosis (DIE) defined as an endometriotic lesion penetrating
      into the retroperitoneal space or the wall of the pelvic organs to a depth of at
      least 5 mm represents the most diagnostic challenge. Herein, we reported the use
      of hyaluronic acid (HA)-modified magnetic iron oxide nanoparticles (HA-Fe3O4 NPs)
      for magnetic resonance (MR) imaging of endometriotic lesions in the rodent model.
      Sixteen endometriotic lesions were surgically induced in eight rats by autologous
      transplantation. Four weeks after lesion induction, three rats were scanned via
      MR imaging after tail vein injection of the HA-Fe3O4 NPs. Accordingly, the
      remaining five mice were sacrificed in the corresponding time points. The ectopic
      uterine tissues (EUTs) were confirmed by histological analysis. Quantification of
      Fe in the EUT was also performed by inductively coupled plasma-optical emission
      spectroscopy. Our results showed that by using the HA-Fe3O4 NPs, the EUTs were
      able to be visualized via T2-weighted MR imaging at 2 hours post injection,
      corroborating the Prussian blue staining results. The developed HA-Fe3O4 NPs
      could be used as negative contrast agents for sensitively detecting endometriosis
      in a mouse model and may be applied for future hyperthermia treatment of
      endometriosis.

PMID- 24722348
TI  - What we observe is biased by what other people tell us: beliefs about the
      reliability of gaze behavior modulate attentional orienting to gaze cues.
AB  - For effective social interactions with other people, information about the
      physical environment must be integrated with information about the interaction
      partner. In order to achieve this, processing of social information is guided by
      two components: a bottom-up mechanism reflexively triggered by stimulus-related
      information in the social scene and a top-down mechanism activated by task
      related context information. In the present study, we investigated whether these
      components interact during attentional orienting to gaze direction. In
      particular, we examined whether the spatial specificity of gaze cueing is
      modulated by expectations about the reliability of gaze behavior. Expectations
      were either induced by instruction or could be derived from experience with
      displayed gaze behavior. Spatially specific cueing effects were observed with
      highly predictive gaze cues, but also when participants merely believed that
      actually non-predictive cues were highly predictive. Conversely, cueing effects
      for the whole gazed-at hemifield were observed with non-predictive gaze cues, and
      spatially specific cueing effects were attenuated when actually predictive gaze
      cues were believed to be non-predictive. This pattern indicates that (i)
      information about cue predictivity gained from sampling gaze behavior across
      social episodes can be incorporated in the attentional orienting to social cues,
      and that (ii) beliefs about gaze behavior modulate attentional orienting to gaze
      direction even when they contradict information available from social episodes. 

PMID- 24722349
TI  - A neutralizing anti-gH/gL monoclonal antibody is protective in the guinea pig
      model of congenital CMV infection.
AB  - Human cytomegalovirus (HCMV) is the most common cause of congenital virus
      infection. Congenital HCMV infection occurs in 0.2-1% of all births, and causes
      birth defects and developmental abnormalities, including sensorineural hearing
      loss and developmental delay. Several key studies have established the guinea pig
      as a tractable model for the study of congenital HCMV infection and have shown
      that polyclonal antibodies can be protective. In this study, we demonstrate that
      an anti-guinea pig CMV (GPCMV) glycoprotein H/glycoprotein L neutralizing
      monoclonal antibody protects against fetal infection and loss in the guinea pig.
      Furthermore, we have delineated the kinetics of GPCMV congenital infection, from
      maternal infection (salivary glands, seroconversion, placenta) to fetal infection
      (fetus and amniotic fluid). Our studies support the hypothesis that a
      neutralizing monoclonal antibody targeting an envelope GPCMV glycoprotein can
      protect the fetus from infection and may shed light on the therapeutic
      intervention of HCMV congenital infection in humans.

PMID- 24722350
TI  - Molecular biological determinations of meningioma progression and recurrence.
AB  - Meningiomas are tumors that arise from the coverings of the brain or spinal cord.
      5% of the cases turn into malignant forms with aggressive clinical behavior and
      increased risk of tumor recurrence. One hundred and five patients with
      meningiomas were operated by open surgery. To investigate predictors of
      meningioma recurrence in total 124 samples of 105 patients were investigated by
      iFISH. Dual-probe hybridization was performed to access chromosomal alterations
      of chromosomes 1p-, 9p- and 22q. Additionally, methylation of TIMP3 and p16 was
      analyzed with MS-PCR. Of the 105 investigated tumors 59.1% (62/105) were WHO
      grade I, 33.3% (35/105) were WHO grade II and 7.7% (8/105) were anaplastic
      meningiomas (grade III), respectively. The histopathological data correlates with
      the recurrence rate of the investigated meningiomas. Hypermethylation of TIMP3
      was detected in 13.3% of all meningiomas: 10.9% in WHO grade I meningiomas, 25.0%
      in grade II and 14.3% in grade III meningiomas, respectively. No correlation of
      TIMP3 hypermethylation with tumor recurrence or WHO grade (p = 0.2) was observed.
      Interestingly, deletion of 1p36 emerged as a significant predictor of shorter
      overall survival (log rank test, p<0.001), whereas TIMP3 promoter methylation had
      no significant effect on overall survival (log rank test, p = 0.799). The results
      of the current study support the finding that the deletion of chromosome 1p is an
      independent marker of meningioma recurrence and progression (p = 0.0097).
      Therefore the measurement of genetic aberrations in meningiomas allows in a
      combined histological approach a more precise assessment of the prognosis of
      meningiomas than histopathology alone.

PMID- 24722351
TI  - Persistence of bactericidal antibodies to 5 years of age after immunization with
      serogroup B meningococcal vaccines at 6, 8, 12 and 40 months of age.
AB  - BACKGROUND: A serogroup B meningococcal vaccine (4CMenB) has been licensed by the
      European commission for use in various infant schedules. However, data are
      limited on persistence of serum bactericidal antibodies (SBA), which is necessary
      to inform cost-effectiveness analysis. METHODS: Sera were obtained from 3 groups
      of 5-year-old children previously immunized at 6, 8, 12 and 40 months with either
      4CMenB or rMenB (which lacks the outer membrane vesicle of 4CMenB) or at 40 and
      42 months with 4CMenB only. Forty-nine control children were also recruited and
      blood obtained before and after 2 doses of 4CMenB at 60 and 62 months of age.
      Sera were tested for SBA to meningococcal B reference strains. RESULTS: At 5
      years of age, 67% of those receiving 4CMenB in infancy had SBA titers >=1:4 for
      strain 44/76, 100% for 5/99, 17% for NZ98/254 and 45% for M10713. Results for
      rMenB recipients varied from 0 (NZ98/254) to 100% (5/99). Of those immunized with
      4CMenB at 40 and 42 months, 38% had SBA titers >=1:4 at age 5 for 44/76, 100% for
      5/99, 0% (NZ98/254) and 83% (M10713). Among controls, SBA titers were >=1:4 in 4%
      (H44/76, 5/99), 0% (NZ98/254) and 67% (M10713) at baseline, increasing to 100%
      (H44/76 and 5/99), 89% (NZ98/254) and 97% (M10713) postimmunization. CONCLUSION:
      The variable rates of waning of antibody to the 4 components of 4CMenB
      complicates estimates of duration of protection and should be taken into account
      in cost-effectiveness analyses. A 2-dose schedule of 4CMenB in 5-year-old
      children was immunogenic.

PMID- 24722352
TI  - Effects of resveratrol on gut microbiota and fat storage in a mouse model with
      high-fat-induced obesity.
AB  - Recent studies have investigated the anti-obesity effect of resveratrol, but the
      pathways through which resveratrol resists obesity are not clear. In the present
      study, we hypothesize that resveratrol exerts anti-obesity effects that are
      likely mediated by mechanisms of regulating gut microbes, and in turn, improving
      fat storage and metabolism. Gut microbes, glucose and lipid metabolism in high
      fat diet (HF) mice in vivo are investigated after resveratrol treatment. Several
      biochemical markers are measured. Fluorescence in situ hybridization and flow
      cytometry are used to monitor and quantify the changes in gut microbiota. The key
      genes related to fat storage and metabolism in the liver and visceral adipose
      tissues are measured by real-time PCR. The results show that resveratrol (200 mg
      per kg per day) significantly lowers both body and visceral adipose weights, and
      reduces blood glucose and lipid levels in HF mice. Resveratrol improves the gut
      microbiota dysbiosis induced by the HF diet, including increasing the
      Bacteroidetes-to-Firmicutes ratios, significantly inhibiting the growth of
      Enterococcus faecalis, and increasing the growth of Lactobacillus and
      Bifidobacterium. Furthermore, resveratrol significantly increases the fasting
      induced adipose factor (Fiaf, a key gene negatively regulated by intestinal
      microbes) expression in the intestine. Resveratrol significantly decreases mRNA
      expression of Lpl, Scd1, Ppar-gamma, Acc1, and Fas related to fatty acids
      synthesis, adipogenesis and lipogenesis, which may be driven by increased Fiaf
      expression. The Pearson's correlation coefficient shows that there is a negative
      correlation between the body weight and the ratios of Bacteroidetes-to
      Firmicutes. Therefore, resveratrol mediates the composition of gut microbes, and
      in turn, through the Fiaf signaling pathway, accelerates the development of
      obesity. 

PMID- 24722353
TI  - Priority of fibular reconstruction in patients with oral cavity cancer undergoing
      segmental mandibulectomy.
AB  - BACKGROUND: The fibula osteoseptocutaneous free flap is generally used for
      segmental mandibular reconstructions following resection of oral cavity squamous
      cell carcinoma (OSCC). However, less complex reconstructions may be feasible for
      patients with predicted poor survival. Herein, we sought to identify the main
      risk factors (RFs) associated with poor prognosis in OSCC patients undergoing
      segmental mandibulectomy to help decide between fibular and non-fibular
      reconstructions. METHODS: Between 1996 and 2011, we examined the 5-year control,
      distant metastases, and survival rates in 310 consecutive, previously untreated
      patients with primary OSCC who underwent segmental mandibulectomy. RESULTS:
      Margin status was the only independent RF for 5-year local control. Level IV/V
      metastases, extracapsular spread, and tumor depth >=15 mm were independent RFs
      for poor 5-year survival. In the entire study cohort, 23% of the patients had 2
      or 3 adverse RFs; such a high-risk group was characterized by a poor prognosis
      and may be suitable for non-fibular reconstructions. Overall, 70% of the study
      patients were cT1-4N0, cT1N2, cT2N1, or had tumor depth <15 mm; less than 5% of
      patients in this subgroup had 2 or 3 adverse RFs and were thus candidates for
      fibular reconstructions. Among the remaining 30% of patients who showed both
      advanced clinical stage (cT2N2, cT3-4N1-2) and tumor depth >=15 mm, 70% exhibited
      2 or 3 adverse RFs. CONCLUSIONS: Level IV/V metastases, extracapsular spread, and
      tumor depth >=15 mm were independent predictors of poor prognosis in OSCC
      patients undergoing segmental mandibulectomy. The preoperative or intraoperative
      identification of adverse RFs may help decide between fibular and non-fibular
      mandibular reconstruction. High-risk patients bearing 2 or 3 adverse RFs have
      poor prognosis and should not be considered as candidates for fibular
      reconstructions.

PMID- 24722354
TI  - ZFP580, a novel zinc-finger transcription factor, is involved in cardioprotection
      of intermittent high-altitude hypoxia against myocardial ischemia-reperfusion
      injury.
AB  - BACKGROUND: ZFP580 is a novel C2H2 type zinc-finger transcription factor recently
      identified by our laboratory. We previously showed that ZFP580 may be involved in
      cell survival and growth. The aim of this study was to elucidate whether ZFP580
      is involved in the cardioprotective effects of intermittent high-altitude (IHA)
      hypoxia against myocardial ischemia-reperfusion (I/R) injury. METHODS AND
      RESULTS: After rats were subjected to myocardial ischemia for 30 min followed by
      reperfusion, ZFP580 expression in the left ventricle was measured. ZFP580 protein
      expression was found to be up-regulated within 1 h and decreased at 2 h after
      reperfusion. Comparing normoxic and IHA hypoxia-adapted rats (5000 m, 6 h day-1,
      6 weeks) following I/R injury (30 min ischemia and 2 h reperfusion), we found
      that adaptation to IHA hypoxia attenuated infarct size and plasma leakage of
      lactate dehydrogenase and creatine kinase-MB. In addition, ZFP580 expression in
      the myocardium was up-regulated by IHA hypoxia. Consistent with this result,
      ZFP580 expression was found to be significantly increased in cultured H9c2
      myocardial cells in the hypoxic preconditioning group compared with those in the
      control group following simulated I/R injury (3 h simulated ischemic hypoxia and
      2 h reoxygenation). To determine the role of ZFP580 in apoptosis, lentivirus
      mediated gene transfection was performed in H9c2 cells 72 h prior to simulated
      I/R exposure. The results showed that ZFP580 overexpression significantly
      inhibited I/R-induced apoptosis and caspase-3 activation. H9c2 cells were
      pretreated with or without PD98059, an inhibitor of ERK1/2 phosphorylation, and
      Western blot results showed that PD98059 (10 uM) markedly suppressed I/R-induced
      up-regulation of ZFP580 expression. CONCLUSIONS: Our findings demonstrate that
      the cardioprotective effect of IHA hypoxia against I/R injury is mediated via
      ZFP580, a downstream target of ERK1/2 signaling with anti-apoptotic roles in
      myocardial cells.

PMID- 24722356
TI  - 37-kDa laminin receptor precursor promotes lung adenocarcinoma cell invasion and
      metastasis by epithelial-to-mesenchymal transition.
AB  - 37-kDa laminin receptor precursor (37LRP) has a crucial role in migration of some
      human cancers. Epithelial-to-mesenchymal transition (EMT) has received much
      attention in invasion and metastasis of lung cancer. Nevertheless, the role of
      37LRP is not entirely clear in EMT promotion of lung cancer at present. In this
      study, we firstly examined the possible role of 37LRP in the invasiveness and
      metastasis process of lung cancer using immunohistochemistry of 80 lung
      adenocarcinoma cases, western blot and real-time PCR of 12 fresh lung
      adenocarcinoma tissues. The results showed that 37LRP significantly correlated
      with clinical stage and were highly expressed in metastatic lung adenocarcinomas
      compared with nonmetastatic ones. In vitro, we observed that 37LRP significantly
      increased the adhesive, invasive and metastatic abilities of human lung
      adenocarcinoma cell lines A549 by 37LRP-lentivirus interference. Furthermore,
      inoculation of A549 cells transduced with 37LRP-lentivirus in nude mice resulted
      in multi-metastases including the lung. In addition, western blotting and
      immunofluorescence were used to detect the significant difference in expression
      of E-cadherin and fibronectin in A549 by 37LRP-lentivirus interference compared
      with 37LRP-small interference RNA-lentivirus interference in vitro and vivo. The
      data indicated that A549 cells of epithelial cell characteristics might be
      induced to undergo EMT by 37LRP. A549 cells transduced with 37LRP-lentivirus
      showed marked morphological changes, accompanied by the decrease of epithelial
      marker E-cadherin and the increase of mesenchymal marker fibronectin. These
      results indicated that 37LRP may promote lung adenocarcinoma invasion and
      metastasis via the mechanism of EMT.

PMID- 24722355
TI  - Activation of the trace amine-associated receptor 1 prevents relapse to cocaine
      seeking.
AB  - The trace amine-associated receptor 1 (TAAR1) has emerged as a promising target
      for medication development in addiction because of its ability to regulate
      dopamine (DA) transmission. We tested in rats the efficacy of RO5203648 and
      RO5256390, partial and full TAAR1 agonists, respectively, in models of cocaine
      relapse. Using a model of context-induced relapse, both RO5203648 and RO5256390
      dose-dependently suppressed cocaine seeking after a 2-week period of withdrawal
      from chronic cocaine self-administration. In a model of extinction-reinstatement,
      RO5203648 completely inhibited cocaine-primed reinstatement of cocaine seeking.
      At doses that effectively suppressed cocaine seeking neither RO5203648 nor
      RO5256390 altered responding maintained by a natural reward. Moreover, fast scan
      cyclic voltammetry data showed that RO5203648 prevented cocaine-induced DA
      overflow in the nucleus accumbens without altering DA half-life, suggesting that
      the partial TAAR1 agonist attenuated cocaine-stimulated DA overflow by mechanisms
      other than direct interference with DA uptake. Collectively, these data provide
      strong evidence in support of TAAR1 as a neuropharmacological target for the
      treatment of cocaine addiction. 

PMID- 24722357
TI  - Cycles of transient high-dose cyclophosphamide administration and intratumoral
      oncolytic adenovirus vector injection for long-term tumor suppression in Syrian
      hamsters.
AB  - Immune responses against oncolytic adenovirus (Ad) vectors are thought to limit
      vector anti-tumor efficacy. With Syrian hamsters, which are immunocompetent and
      whose tumors and normal tissues are permissive for replication of Ad5-based
      oncolytic Ad vectors, treating with high-dose cyclophosphamide (CP) to suppress
      the immune system and exert chemotherapeutic effects enhances Ad vector anti
      tumor efficacy. However, long-term CP treatment and immunosuppression can lead to
      anemia and vector spread to normal tissues. Here, we employed three cycles of
      transient high-dose CP administration plus intratumoral injection of the
      oncolytic Ad vector VRX-007 followed by withdrawal of CP. Each cycle lasted 4-6
      weeks. This protocol allowed the hamsters to remain healthy so the study could be
      continued for ~100 days. The tumors were very well suppressed throughout the
      study. With immunocompetent hamsters, the vector retarded tumor growth initially,
      but after 3-4 weeks the tumors resumed rapid growth and further injections of
      vector were ineffective. Preimmunization of the hamsters with Ad5 prevented
      vector spillover from the tumor to the liver yet still allowed for effective long
      term anti-tumor efficacy. Our results suggest that a clinical protocol might be
      developed with cycles of transient chemotherapy plus intratumoral vector
      injection to achieve significant anti-tumor efficacy while minimizing the side
      effects of cytostatic treatment.

PMID- 24722359
TI  - Sensing membrane stresses by protein insertions.
AB  - Protein domains shallowly inserting into the membrane matrix are ubiquitous in
      peripheral membrane proteins involved in various processes of intracellular
      membrane shaping and remodeling. It has been suggested that these domains sense
      membrane curvature through their preferable binding to strongly curved membranes,
      the binding mechanism being mediated by lipid packing defects. Here we make an
      alternative statement that shallow protein insertions are universal sensors of
      the intra-membrane stresses existing in the region of the insertion embedding
      rather than sensors of the curvature per se. We substantiate this proposal
      computationally by considering different independent ways of the membrane stress
      generation among which some include changes of the membrane curvature whereas
      others do not alter the membrane shape. Our computations show that the membrane
      binding coefficient of shallow protein insertions is determined by the resultant
      stress independently of the way this stress has been produced. By contrast,
      consideration of the correlation between the insertion binding and the membrane
      curvature demonstrates that the binding coefficient either increases or decreases
      with curvature depending on the factors leading to the curvature generation. To
      validate our computational model, we treat quantitatively the experimental
      results on membrane binding by ALPS1 and ALPS2 motifs of ArfGAP1. 

PMID- 24722358
TI  - PCR-based techniques for leprosy diagnosis: from the laboratory to the clinic.
AB  - In leprosy, classic diagnostic tools based on bacillary counts and histopathology
      have been facing hurdles, especially in distinguishing latent infection from
      active disease and diagnosing paucibacillary clinical forms. Serological tests
      and IFN-gamma releasing assays (IGRA) that employ humoral and cellular immune
      parameters, respectively, are also being used, but recent results indicate that
      quantitative PCR (qPCR) is a key technique due to its higher sensitivity and
      specificity. In fact, advances concerning the structure and function of the
      Mycobacterium leprae genome led to the development of specific PCR-based gene
      amplification assays for leprosy diagnosis and monitoring of household contacts.
      Also, based on the validation of point-of-care technologies for M. tuberculosis
      DNA detection, it is clear that the same advantages of rapid DNA detection could
      be observed in respect to leprosy. So far, PCR has proven useful in the
      determination of transmission routes, M. leprae viability, and drug resistance in
      leprosy. However, PCR has been ascertained to be especially valuable in
      diagnosing difficult cases like pure neural leprosy (PNL), paucibacillary (PB),
      and patients with atypical clinical presentation and histopathological features
      compatible with leprosy. Also, the detection of M. leprae DNA in different
      samples of the household contacts of leprosy patients is very promising. Although
      a positive PCR result is not sufficient to establish a causal relationship with
      disease outcome, quantitation provided by qPCR is clearly capable of indicating
      increased risk of developing the disease and could alert clinicians to follow
      these contacts more closely or even define rules for chemoprophylaxis. 

PMID- 24722360
TI  - Mapping of topological quantum circuits to physical hardware.
AB  - Topological quantum computation is a promising technique to achieve large-scale,
      error-corrected computation. Quantum hardware is used to create a large, 3
      dimensional lattice of entangled qubits while performing computation requires
      strategic measurement in accordance with a topological circuit specification. The
      specification is a geometric structure that defines encoded information and fault
      tolerant operations. The compilation of a topological circuit is one important
      aspect of programming a quantum computer, another is the mapping of the
      topological circuit into the operations performed by the hardware. Each qubit has
      to be controlled, and measurement results are needed to propagate encoded quantum
      information from input to output. In this work, we introduce an algorithm for
      mapping an topological circuit to the operations needed by the physical hardware.
      We determine the control commands for each qubit in the computer and the relevant
      measurements that are needed to track information as it moves through the
      circuit. 

PMID- 24722361
TI  - How the impact of median neuropathy on sensorimotor control capability of hands
      for diabetes: an achievable assessment from functional perspectives.
AB  - To comprehend the sensorimotor control ability in diabetic hands, this study
      investigated the sensation, motor function and precision pinch performances
      derived from a pinch-holding-up activity (PHUA) test of the hands of diabetic
      patients and healthy subjects. The precision, sensitivity and specificity of the
      PHUA test in the measurements of diabetic patients were also analyzed. We
      hypothesized that the diabetic hands would have impacts on the sensorimotor
      functions of the hand performances under functionally quantitative measurements.
      One hundred and fifty-nine patients with clinically defined diabetes mellitus
      (DM) and 95 age- and gender-matched healthy controls were included. Semmes
      Weinstein monofilament (SWM), static and moving two-point discrimination (S2PD
      and M2PD), maximal pinch strength and precision pinch performance tests were
      conducted to evaluate the sensation, motor and sensorimotor status of the
      recruited hands. The results showed that there were significant differences (all
      p<0.05) in SWM, S2PD, M2PD and maximum pinch strength between the DM and control
      groups. A higher force ratio in the DM patients than in the controls (p<0.001)
      revealed a poor ability of pinch force adjustment in the DM patients. The
      percentage of maximal pinch strength was also significantly different (p<0.001)
      between the DM and control groups. The sensitivity, specificity and area under
      the receiver operating characteristic curve were 0.85, 0.51, and 0.724,
      respectively, for the PHUA test. Statistically significant degradations in
      sensory and motor functions and sensorimotor control ability were observed in the
      hands of the diabetic patients. The PHUA test could be feasibly used as a
      clinical tool to determine the sensorimotor function of the hands of diabetic
      patients from a functional perspective. 

PMID- 24722362
TI  - Cadmium stress disrupts the endomembrane organelles and endocytosis during Picea
      wilsonii pollen germination and tube growth.
AB  - As one of the most severe pollutants, cadmium has been reported to be harmful to
      plant cells, but the effects of cadmium on gymnosperm pollen germination and tube
      growth and the mechanism of this involvement are still unclear. Here, we report
      that cadmium not only strongly inhibited P. wilsonii pollen germination and tube
      growth, but also significantly altered tube morphology in a dose-dependent
      manner. Time-lapse images obtained with a laser scanning confocal microscope
      revealed that endocytosis was dramatically inhibited by cadmium stress. Further
      investigation with ER-Tracker dye indicated that cadmium stress reduced the
      number of the Golgi apparatus, and induced dilation of ER. Additionally, Lyso
      Tracker staining showed that cadmium distinctly promoted the formation of acidic
      organelles in pollen tubes, likely derived from the dilated ER. Taken together,
      our studies indicated that P. wilsonii pollens were highly susceptible to cadmium
      stress, and that cadmium stress strongly inhibited pollen germination and tube
      growth by disrupting the endomembrane organelles, inhibiting endo/exocytosis, and
      forming acidic vacuoles, resulting in swollen tube tips and irregularly broadened
      tube diameters. These findings provide a new insight into the effects of cadmium
      toxicity on the tip growth of pollen tubes.

PMID- 24722363
TI  - Influence of noise correction on intra- and inter-subject variability of
      quantitative metrics in diffusion kurtosis imaging.
AB  - Diffusion kurtosis imaging (DKI) is a promising extension of diffusion tensor
      imaging, giving new insights into the white matter microstructure and providing
      new biomarkers. Given the rapidly increasing number of studies, DKI has a
      potential to establish itself as a valuable tool in brain diagnostics. However,
      to become a routine procedure, DKI still needs to be improved in terms of
      robustness, reliability, and reproducibility. As it requires acquisitions at
      higher diffusion weightings, results are more affected by noise than in diffusion
      tensor imaging. The lack of standard procedures for post-processing, especially
      for noise correction, might become a significant obstacle for the use of DKI in
      clinical routine limiting its application. We considered two noise correction
      schemes accounting for the noise properties of multichannel phased-array coils,
      in order to improve the data quality at signal-to-noise ratio (SNR) typical for
      DKI. The SNR dependence of estimated DKI metrics such as mean kurtosis (MK), mean
      diffusivity (MD) and fractional anisotropy (FA) is investigated for these noise
      correction approaches in Monte Carlo simulations and in in vivo human studies.
      The intra-subject reproducibility is investigated in a single subject study by
      varying the SNR level and SNR spatial distribution. Then the impact of the noise
      correction on inter-subject variability is evaluated in a homogeneous sample of
      25 healthy volunteers. Results show a strong impact of noise correction on the MK
      estimate, while the estimation of FA and MD was affected to a lesser extent. Both
      intra- and inter-subject SNR-related variability of the MK estimate is
      considerably reduced after correction for the noise bias, providing more accurate
      and reproducible measures. In this work, we have proposed a straightforward
      method that improves accuracy of DKI metrics. This should contribute to
      standardization of DKI applications in clinical studies making valuable
      inferences in group analysis and longitudinal studies. 

PMID- 24722364
TI  - Platelet dynamics during natural and pharmacologically induced torpor and forced
      hypothermia.
AB  - Hibernation is an energy-conserving behavior in winter characterized by two
      phases: torpor and arousal. During torpor, markedly reduced metabolic activity
      results in inactivity and decreased body temperature. Arousal periods intersperse
      the torpor bouts and feature increased metabolism and euthermic body temperature.
      Alterations in physiological parameters, such as suppression of hemostasis, are
      thought to allow hibernators to survive periods of torpor and arousal without
      organ injury. While the state of torpor is potentially procoagulant, due to low
      blood flow, increased viscosity, immobility, hypoxia, and low body temperature,
      organ injury due to thromboembolism is absent. To investigate platelet dynamics
      during hibernation, we measured platelet count and function during and after
      natural torpor, pharmacologically induced torpor and forced hypothermia.
      Splenectomies were performed to unravel potential storage sites of platelets
      during torpor. Here we show that decreasing body temperature drives
      thrombocytopenia during torpor in hamster with maintained functionality of
      circulating platelets. Interestingly, hamster platelets during torpor do not
      express P-selectin, but expression is induced by treatment with ADP. Platelet
      count rapidly restores during arousal and rewarming. Platelet dynamics in
      hibernation are not affected by splenectomy before or during torpor. Reversible
      thrombocytopenia was also induced by forced hypothermia in both hibernating
      (hamster) and non-hibernating (rat and mouse) species without changing platelet
      function. Pharmacological torpor induced by injection of 5'-AMP in mice did not
      induce thrombocytopenia, possibly because 5'-AMP inhibits platelet function. The
      rapidness of changes in the numbers of circulating platelets, as well as marginal
      changes in immature platelet fractions upon arousal, strongly suggest that
      storage-and-release underlies the reversible thrombocytopenia during natural
      torpor. Possibly, margination of platelets, dependent on intrinsic platelet
      functionality, governs clearance of circulating platelets during torpor. 

PMID- 24722366
TI  - Recent progress in the utility of anti-Mullerian hormone in female infertility.
AB  - PURPOSE OF REVIEW: To discuss the recent developments in the utility of anti
      Mullerian hormone (AMH) in the context of female infertility. RECENT FINDINGS:
      AMH measurements have entered the clinical practice in counseling of women before
      in-vitro fertilization (IVF) treatment. AMH measurements can predict both poor
      and hyperresponse, and can enable clinicians to individualize the treatment
      strategies. In natural conception, AMH is a good predictor of age at menopause,
      but it is unclear whether AMH correlates with the fecund ability in the normal
      population. AMH has also proven its utility in the assessment of ovarian damage
      due to gonadotoxic treatment or ovarian surgery. Lastly, AMH might assist in the
      initial diagnosis of oligomenorrhea or amenorrhea, as high levels of AMH are
      suggestive of polycystic ovarian syndrome and seem to correlate with the severity
      of the syndrome. SUMMARY: AMH is a glycoprotein secreted by the granulosa cells
      of small growing follicles and indirectly reflects the primordial follicle pool.
      The ovaries contain a limited number of primordial follicles and their depletion
      marks the menopause. Thus, the remaining primordial follicle pool is referred to
      as the ovarian reserve. The clearest data for the clinical utility of AMH is in
      the context of IVF. The support for other indications is weaker, but rapidly
      increasing.

PMID- 24722365
TI  - A quantitative high-resolution genetic profile rapidly identifies sequence
      determinants of hepatitis C viral fitness and drug sensitivity.
AB  - Widely used chemical genetic screens have greatly facilitated the identification
      of many antiviral agents. However, the regions of interaction and inhibitory
      mechanisms of many therapeutic candidates have yet to be elucidated. Previous
      chemical screens identified Daclatasvir (BMS-790052) as a potent nonstructural
      protein 5A (NS5A) inhibitor for Hepatitis C virus (HCV) infection with an unclear
      inhibitory mechanism. Here we have developed a quantitative high-resolution
      genetic (qHRG) approach to systematically map the drug-protein interactions
      between Daclatasvir and NS5A and profile genetic barriers to Daclatasvir
      resistance. We implemented saturation mutagenesis in combination with next
      generation sequencing technology to systematically quantify the effect of every
      possible amino acid substitution in the drug-targeted region (domain IA of NS5A)
      on replication fitness and sensitivity to Daclatasvir. This enabled determination
      of the residues governing drug-protein interactions. The relative fitness and
      drug sensitivity profiles also provide a comprehensive reference of the genetic
      barriers for all possible single amino acid changes during viral evolution, which
      we utilized to predict clinical outcomes using mathematical models. We envision
      that this high-resolution profiling methodology will be useful for next
      generation drug development to select drugs with higher fitness costs to
      resistance, and also for informing the rational use of drugs based on viral
      variant spectra from patients. 

PMID- 24722367
TI  - Y-tocotrienol inhibits angiogenesis-dependent growth of human hepatocellular
      carcinoma through abrogation of AKT/mTOR pathway in an orthotopic mouse model.
AB  - Angiogenesis is one of the key hallmarks of cancer. In this study, we
      investigated whether gamma-tocotrienol can abrogate angiogenesis-mediated tumor
      growth in hepatocellular carcinoma (HCC) and if so, through what molecular
      mechanisms. We observed that gamma-tocotrienol inhibited vascular endothelial
      growth factor (VEGF)-induced migration, invasion, tube formation and viability of
      HUVECs in vitro. Moreover, gamma-tocotrienol reduced the number of capillary
      sprouts from matrigel embedded rat thoracic aortic ring in a dose-dependent
      manner. Also, in chick chorioallantoic membrane assay, gamma-tocotrienol
      significantly reduced the blood vessels formation. We further noticed that gamma
      tocotrienol blocked angiogenesis in an in vivo matrigel plug assay. Furthermore,
      gamma-tocotrienol inhibited VEGF-induced autophosphorylation of VEGFR2 in HUVECs
      and also suppressed the constitutive activation of AKT/mammalian target of
      rapamycin (mTOR) signal transduction cascades in HUVECs as well as in HCC cells.
      Interestingly, gamma-tocotrienol was also found to significantly reduce the tumor
      growth in an orthotopic HCC mouse model and inhibit tumor-induced angiogenesis in
      HCC patient xenografts through the suppression of various biomarkers of
      proliferation and angiogenesis. Taken together, our findings strongly suggest
      that gamma-tocotrienol might be a promising anti-angiogenic drug with significant
      antitumor activity in HCC. 

PMID- 24722368
TI  - Functionally distinct effects of the C-terminal regions of IKKepsilon and TBK1 on
      type I IFN production.
AB  - Inhibitor of kappaB kinase epsilon (IKKepsilon) and TANK binding kinase 1 (TBK1),
      so-called non-canonical IKKs or IKK-related kinases, are involved in the cellular
      innate immunity by inducing type I IFNs. Two kinases commonly phosphorylate
      transcription factors IRF3 and IRF7 in type I IFN production pathway. In contrast
      to TBK1, underlying mechanisms of IKKepsilon activation and regions required for
      activation of downstream molecules are poorly understood. In this study, we
      investigated regions of IKKepsilon required for the activation of type I IFN
      promoter specially, by focusing on the C-terminal region. To show the functional
      significance of the IKKepsilon C-terminal region on type I IFN production, we
      employed various mutant forms of IKKepsilon and compared to corresponding region
      of TBK1. We identified the specific regions and residues of IKKepsilon involved
      in the activation of downstream signaling. Interestingly, corresponding region
      and residues are not required for activation of downstream signaling by TBK1. The
      results highlight the importance of the C-terminal region in the functional
      activity of IKKepsilon in innate immune response and also the difference in
      activation mechanisms between IKKepsilon and the closely related TBK1.

PMID- 24722369
TI  - A system for household enumeration and re-identification in densely populated
      slums to facilitate community research, education, and advocacy.
AB  - BACKGROUND: We devised and implemented an innovative Location-Based Household
      Coding System (LBHCS) appropriate to a densely populated informal settlement in
      Mumbai, India. METHODS AND FINDINGS: LBHCS codes were designed to double as
      unique household identifiers and as walking directions; when an entire community
      is enumerated, LBHCS codes can be used to identify the number of households
      located per road (or lane) segment. LBHCS was used in community-wide biometric,
      mental health, diarrheal disease, and water poverty studies. It also facilitated
      targeted health interventions by a research team of youth from Mumbai, including
      intensive door-to-door education of residents, targeted follow-up meetings, and a
      full census. In addition, LBHCS permitted rapid and low-cost preparation of GIS
      mapping of all households in the slum, and spatial summation and spatial analysis
      of survey data. CONCLUSION: LBHCS was an effective, easy-to-use, affordable
      approach to household enumeration and re-identification in a densely populated
      informal settlement where alternative satellite imagery and GPS technologies
      could not be used.

PMID- 24722371
TI  - A novel technique for the production of electrospun scaffolds with tailored three
      dimensional micro-patterns employing additive manufacturing.
AB  - Electrospinning is a common technique used to fabricate fibrous scaffolds for
      tissue engineering applications. There is now growing interest in assessing the
      ability of collector plate design to influence the patterning of the fibres
      during the electrospinning process. In this study, we investigate a novel method
      to generate hybrid electrospun scaffolds consisting of both random fibres and a
      defined three-dimensional (3D) micro-topography at the surface, using patterned
      resin formers produced by rapid prototyping (RP). Poly(D,L-lactide-co-glycolide)
      was electrospun onto the engineered RP surfaces and the ability of these formers
      to influence microfibre patterning in the resulting scaffolds visualized by
      scanning electron microscopy. Electrospun scaffolds with patterns mirroring the
      microstructures of the formers were successfully fabricated. The effect of the
      resulting fibre patterns and 3D geometries on mammalian cell adhesion and
      proliferation was investigated by seeding enhanced green fluorescent protein
      labelled 3T3 fibroblasts onto the scaffolds. Following 24 h and four days of
      culture, the seeded scaffolds were visually assessed by confocal macro- and
      microscopy. The patterning of the fibres guided initial cell adhesion to the
      scaffold with subsequent proliferation over the geometry resulting in the cells
      being held in a 3D micro-topography. Such patterning could be designed to
      replicate a specific in vivo structure; we use the dermal papillae as an exemplar
      here. In conclusion, a novel, versatile and scalable method to produce hybrid
      electrospun scaffolds has been developed. The 3D directional cues of the
      patterned fibres have been shown to influence cell behaviour and could be used to
      culture cells within a similar 3D micro-topography as experienced in vivo.

PMID- 24722370
TI  - Raloxifene suppresses experimental autoimmune encephalomyelitis and NF-kappaB
      dependent CCL20 expression in reactive astrocytes.
AB  - Recent clinical data have led to the consideration of sexual steroids as new
      potential therapeutic tools for multiple sclerosis. Selective estrogen receptor
      modulators can exhibit neuroprotective effects like estrogen, with fewer systemic
      estrogen side effects than estrogen, offering a more promising therapeutic
      modality for multiple sclerosis. The important role of astrocytes in a
      proinflammatory effect mediated by CCL20 signaling on inflammatory cells has been
      documented. Their potential contribution to selective estrogen receptor modulator
      mediated protection is still unknown. Using a mouse model of chronic
      neuroinflammation, we report that raloxifene, a selective estrogen receptor
      modulator, alleviated experimental autoimmune encephalomyelitis-an animal model
      of multiple sclerosis-and decreased astrocytic production of CCL20. Enzyme-linked
      immunosorbent assay, immunohistochemistry imaging and transwell migration assays
      revealed that reactive astrocytes express CCL20, which promotes Th17 cell
      migration. In cultured rodent astrocytes, raloxifene inhibited IL-1beta-induced
      CCL20 expression and chemotaxis ability for Th17 migration, whereas the estrogen
      receptor antagonist ICI 182,780 blocked this effect. Western blotting further
      indicated that raloxifene suppresses IL-1beta-induced NF-kappaB activation
      (phosphorylation of p65) and translocation but does not affect phosphorylation of
      IkappaB. In conclusion, these data demonstrate that raloxifene provides robust
      neuroprotection against experimental autoimmune encephalomyelitis, partially via
      an inhibitory action on CCL20 expression and NF-kappaB pathways in reactive
      astrocytes. Our results contribute to a better understanding of the critical
      roles of raloxifene in treating experimental autoimmune encephalomyelitis and
      uncover reactive astrocytes as a new target for the inhibitory action of estrogen
      receptors on chemokine CCL20 expression. 

PMID- 24722372
TI  - An enantioselective amidase from Burkholderia multivorans for the stereoselective
      synthesis of esfenvalerate.
AB  - Using racemic (R,S)-2-(4-chlorophenyl)-3-methylbutyramide, an intermediate for
      the chiral pyrethroid insecticide Esfenvalerate, as a sole nitrogen source in a
      minimal medium, several strains with high enatioselectivity (>=98%) were isolated
      by enrichment techniques. One of the strains, LG 31-3, was identified as
      Burkholderia multivorans, based on physiological and morphological tests by a
      standardized Biolog station for carbon source utilization. A novel amidase was
      purified from B. mutivorans LG 31-3 and characterized. The enzyme exhibited (S)-
      selective amidase activity on racemic (R,S)-2-(4-chlorophenyl)-3
      methylbutyramide. Addition of the racemic amide induced the production of the
      enantioselective amidase. The molecular mass of the amidase on SDS-PAGE analysis
      was shown to be 50 kDa. The purified amidase was subjected to proteolytic
      digestion with a modified trypsin. The N-terminal and internal amino acid
      sequences of the purified amidase showed a high sequence homology with those
      deduced from a gene named YP_366732.1 encoding indole acetimide hydrolase from
      Burkholderia sp. 383. 

PMID- 24722373
TI  - A highly active alpha amylase from Bacillus licheniformis: directed evolution,
      enzyme characterization and structural analysis.
AB  - The stability of Bacillus licheniformis alpha-amylase (BLA) under acid condition
      was enhanced through direct evolution using the error-prone polymerase chain
      reaction. One beneficial mutation site, H281I, was obtained in BLA. The specific
      activity of H281I was 161/352 U/mg, which was 62.6/27.5% higher than that of the
      wild-type (WT) (99/276 U/mg) at pH 4.5/6.5 and 95 degrees C. The pH optimum for
      H281I was decreased about 1 unit, whereas no significant changes of optimum
      temperature and thermostability were observed compared with the wild type (WT).
      The kcat/Km value of H281I was 1.7-/1.4-fold higher at pH 4.5/6.5, respectively,
      than that of WT. The structure model analysis indicated that the H281I mutation
      altered the predicted interaction between the amino acid residues at 281 and 273,
      thus creating a conducive local environment for substrate binding, as reflected
      by its decreased Km, and consequently increased the specific activity. 

PMID- 24722374
TI  - CTX prophages in Vibrio cholerae O1 strains.
AB  - The classical biotype strains of the Vibrio cholerae O1 serogroup harbor the
      biotype-specific cholera-toxin encoding phage (CTX) CTX(cla), and the El Tor
      biotype strains contain CTX-1. Although the classical biotype strains have become
      extinct, a remnant of classical CTX phage is transferred to the El Tor biotype
      strains. The prototype El Tor strains, which produce the biotype-specific cholera
      toxin, are now being replaced by atypical El Tor variant strains producing
      classical biotype cholera toxin. The genome sequences of the CTX phages in
      atypical El Tor strains indicate that the CTX phages in atypical El Tor strains
      are a mosaic of CTXcla and CTX-1. Before the emergence of atypical El Tor stains
      in the early 1990s, unusual pre-seventh pandemic strains were isolated in the US
      Gulf Coast between 1973 and 1986. These strains have characteristics of atypical
      El Tor strains since they are El Tor biotype strains containing CTX(cla), yet the
      genome sequence of this CTX phage indicates that it is different from CTXcla and
      is therefore classified separately as CTX(US Gulf). 

PMID- 24722375
TI  - Expression and purification of a functional recombinant aspartate
      aminotransferase (AST) from Escherichia coli.
AB  - Aspartate aminotransferase (AST; E.C. 2.6.1.1), a vitamin B6-dependent enzyme,
      preferentially promotes the mutual transformation of aspartate and alpha
      ketoglutarate to oxaloacetate and glutamate. It plays a key role in amino acid
      metabolism and has been widely recommended as a biomarker of liver and heart
      damage. Our study aimed to evaluate the extensive preparation of AST and its
      application in quality control in clinical laboratories. We describe a scheme to
      express and purify the 6His-AST fusion protein. An optimized sequence coding AST
      was synthesized and transformed into Escherichia coli BL21 (DE3) strain for
      protein expression. Ideally, the fusion protein has a volumetric productivity
      achieving 900 mg/l cultures. After affinity chromatography, the enzyme activity
      of purified AST reached 150,000 U/L. Commutability assessment between the
      engineered AST and standard AST from Roche suggested that the engineered AST was
      the better candidate for the reference material. Moreover, the AST showed high
      stability during long-term storage at -20oC. In conclusion, the highly soluble
      6His-tagged AST can become a convenient tool for supplying a much better and
      cheaper standard or reference material for the clinical laboratory. 

PMID- 24722376
TI  - Development of a novel long-range 16S rRNA universal primer set for metagenomic
      analysis of gastrointestinal microbiota in newborn infants.
AB  - Metagenomic analysis of the human intestinal microbiota has extended our
      understanding of the role of these bacteria in improving human intestinal health;
      however, a number of reports have shown that current total fecal DNA extraction
      methods and 16S rRNA universal primer sets could affect the species coverage and
      resolution of these analyses. Here, we improved the extraction method for total
      DNA from human fecal samples by optimization of the lysis buffer, boiling time
      (10 min), and bead-beating time (0 min). In addition, we developed a new
      longrange 16S rRNA universal PCR primer set targeting the V6 to V9 regions with a
      580 bp DNA product length. This new 16S rRNA primer set was evaluated by
      comparison with two previously developed 16S rRNA universal primer sets and
      showed high species coverage and resolution. The optimized total fecal DNA
      extraction method and newly designed long-range 16S rRNA universal primer set
      will be useful for the highly accurate metagenomic analysis of adult and infant
      intestinal microbiota with minimization of any bias. 

PMID- 24722377
TI  - Chalcones suppress fatty acid-induced lipid accumulation through a LKB1/AMPK
      signaling pathway in HepG2 cells.
AB  - Excessive lipid accumulation in the liver has been proposed to cause
      hyperlipidemia, diabetes and fatty liver disease. 4-Hydroxyderricin (4HD),
      xanthoangelol (XAG), cardamonin (CAR) and flavokawain B (FKB) are chalcones that
      have exhibited various biological effects against obesity, inflammation, and
      diabetes; however, little is known about the inhibitory effects of these
      chalcones on fatty liver disease. In the present study, we investigated the
      ability of 4HD, XAG, CAR, and FKB to reduce lipid accumulation in hepatocytes.
      When HepG2 cells were treated with a mixture of fatty acids (FAs; palmitic acid :
      oleic acid = 1 : 2 ratio), significant lipid accumulation was observed. Under the
      same experimental conditions, addition of chalcones at 5 MUM significantly
      suppressed the FA-induced lipid accumulation. We found that the expression of
      sterol regulatory element-binding protein-1 (SREBP-1), a key molecule involved in
      lipogenesis, was decreased in these chalcone-treated cells. We also found that
      these chalcones increased the expression of peroxisome proliferator-activated
      receptor alpha (PPARalpha), which is involved in FA oxidation. Moreover, these
      chalcones increased phosphorylation of AMP-activated protein kinase (AMPK) and
      liver kinase B1 (LKB1), upstream regulators of SREBP-1 and PPARalpha. We
      confirmed that an AMPK inhibitor, compound C, reversed chalcone-induced changes
      in SREBP-1 and PPARalpha expression in the HepG2 cells. Collectively, we found
      that 4HD, XAG, CAR, and XAG attenuated lipid accumulation through activation of
      the LKB1/AMPK signaling pathway in HepG2 cells.

PMID- 24722379
TI  - Evaluation of diagnostic serological results in cases of suspected primary
      syphilis infection.
AB  - BACKGROUND: Reverse sequence screening for syphilis, in which an automatable
      treponemal assay (enzyme immunoassay [EIA]/chemiluminescence assay [CIA]) is
      performed first and followed by a nontreponemal test for reactive specimens, has
      been used increasingly in the United States. The EIA is objective, efficient, and
      believed to be more sensitive than the rapid plasma reagin (RPR) because
      treponemal antibodies appear before nontreponemal antibodies. We sought to
      compare the sensitivity of a commonly used EIA, the Trep-Sure EIA (TS-EIA), to
      the RPR in cases of suspected primary syphilis infection in our clinic. METHODS:
      A retrospective medical record review of patients with sexually transmitted
      infection clinic visits from January 2009 to December 2011 was conducted, and 52
      patients met the following inclusion criteria: suspected primary syphilis
      symptoms, at least 1 positive syphilis test result at visit, and no history of
      syphilis. Sensitivity analyses compared the TS-EIA and RPR, using the reference
      standard of concordantly positive/reactive TS-EIA/RPR or positive fluorescent
      treponemal antibody absorption test (FTA-ABS) result. We considered equivocal TS
      EIA results to be positive for sensitivity calculations because such results
      typically reflex to additional testing and therefore may still result in
      identifying new infections. RESULTS: Twenty-eight (53.8%) of the 52 patients had
      a positive or equivocal TS-EIA. Twenty-five (89.3%) of those were RPR reactive;
      the remaining 3 (10.7%) were RPR nonreactive, FTA-ABS positive. Forty patients
      (76.9%) had a positive RPR, including 15 patients (37.5%) with negative TS-EIA
      results; all 15 were FTA-ABS positive. Nine additional patients were TS-EIA
      negative and RPR nonreactive but had a positive FTA-ABS result. The RPR was
      significantly more sensitive than the EIA (76.9% vs. 53.8%, P = 0.005). Trep-Sure
      EIA positivity was also significantly associated with higher median RPR titer (P
      = 0.011). CONCLUSIONS: Use of the TS-EIA may result in underdetection of primary
      syphilis compared with the RPR. Further evaluation of the sensitivity of the TS
      EIA in high-morbidity settings is warranted before the adoption of reverse
      sequence screening algorithms.

PMID- 24722378
TI  - Serum levels of interleukin-9 correlate with negative prognostic factors in
      extranodal NK/T-cell lymphoma.
AB  - Interleukin-9 (IL-9) is more functionally diverse than previously expected,
      especially with regards to lymphomagenesis. However, the relationship between IL
      9 and the clinicopathological features of extranodal NK/T-cell lymphoma is less
      well established. Patients with this lymphoma in Sun Yat-Sen University Cancer
      Center between January 2003 and March 2013 were systematically reviewed in an
      intention-to-treat analysis. Baseline serum IL-9 levels were determined using
      sandwich enzyme-linked immunosorbent assays. A total of seventy-four patients
      were enrolled in this study. The mean concentration of serum IL-9 for all
      patients was 6.48 pg/mL (range: 1.38-51.87 pg/mL). Age, B symptoms and local
      lymph node involvement were found to be related to high serum IL-9 levels.
      Patients with low IL-9 levels tended to have higher rates of complete remission.
      Notably, the median progression-free survival (PFS) and overall survival (OS)
      were longer in the low IL-9 level group than in the high IL-9 level group (PFS:
      68.7 months vs. 28.3 months, P<0.001; OS: 86 months vs. 42.8 months, P = 0.001).
      Multivariate analysis revealed independent prognostic factors for PFS. Similarly,
      high IL-9 levels (P = 0.003) and old age (P = 0.007) were independently
      predictive of shorter OS. Serum IL-9 is closely related to several clinical
      features, such as age, B symptoms and local lymph node involvement. It can also
      be a significant independent prognostic factor for extranodal NK/T-cell lymphoma,
      which suggests a role for IL-9 in the pathogenesis of this disease and offers new
      insight into potential therapeutic strategies.

PMID- 24722380
TI  - High-dose vaginal maintenance metronidazole for recurrent bacterial vaginosis: a
      pilot study.
AB  - The purpose of this study was to explore the benefit of high-dose intravaginal
      metronidazole as a maintenance therapy in reducing recurrence rates of bacterial
      vaginosis (BV). Eighteen women with a history of recurrent BV and symptomatic BV
      were treated with metronidazole 750 mg suppository intravaginally daily for 7
      days. Those in remission by Amsel criteria received metronidazole 750 mg twice
      weekly for 3 months with further follow-up for 3 months. High-dose metronidazole
      intravaginally was associated with rare clinical recurrence during the period of
      use. After cessation of suppression therapy, recurrence was high.

PMID- 24722381
TI  - Comparing the prevalence of condylomata acuminata between pregnant women and
      nonpregnant controls in South Korea: a population-based, cross-sectional study.
AB  - We analyzed and estimated the prevalence of condylomata acuminata from South
      Korea claim data in 2009. The prevalence in pregnant women aged 20 to 34 years
      (46 +/- 7 per 100,000 persons) was lower than that in nonpregnant women aged 20
      to 34 years (59 +/- 1 per 100,000 persons; P < 0.001). 

PMID- 24722382
TI  - Bacterial vaginosis and season, a proxy for vitamin D status.
AB  - BACKGROUND: Low serum vitamin D concentration has been associated with increased
      prevalence of bacterial vaginosis (BV) among pregnant women, but the few studies
      conducted in nonpregnant women have produced inconsistent results. Because serum
      vitamin D concentration is generally higher in the summer and fall than winter
      and spring, if vitamin D insufficiency causes BV, then BV would be expected to be
      more common during seasons with lower vitamin D concentrations. METHODS: The
      Longitudinal Study of Vaginal Flora followed up women in Birmingham, Alabama
      (33.5 degrees  latitude), quarterly for up to 1 year. We used a case-crossover
      design with conditional logistic regression among women who attended visits in
      each season, to assess the adjusted association between season and BV. We
      compared each woman's BV status in summer, fall, and spring to her own status in
      winter. RESULTS: Among the 3620 women in the parent study, 2337 attended visits
      in each season; BV prevalence was 40% in winter, 38% in spring, and 41% in summer
      and fall. One thousand three hundred thirty-five women had BV at some but not all
      visits and were therefore included in the case-crossover analysis. Season was not
      associated with BV in women who were BV negative at study entry (odds ratio vs.
      winter were 1.0 for spring, 1.0 for summer, and 0.9 for fall; P = 0.81). Among
      women BV positive at study entry, the corresponding odds ratios were 0.9, 1.4,
      and 1.4 (P < 0.001). CONCLUSIONS: These results do not support an association
      between vitamin D, measured through the proxy variable of season, and BV.

PMID- 24722383
TI  - Estimating the incidence and prevalence of juvenile-onset recurrent respiratory
      papillomatosis in publicly and privately insured claims databases in the United
      States.
AB  - BACKGROUND: Juvenile-onset recurrent respiratory papillomatosis (JORRP) is a
      chronic disease caused by human papillomavirus types 6 and 11. It is associated
      with significant morbidity that places intense physical, psychological, and
      financial strain on patients and their families. Few studies have assessed the
      incidence and prevalence of JORRP in the United States. METHODS: This
      retrospective, longitudinal cohort study was performed using data from a pair of
      large insurance claims databases in the United States. The Optum Clinformatics
      and Truven MarketScan Medicaid databases represent a sample of privately and
      publicly insured children, respectively. Cohorts of children aged 0 to 17 years
      were created within each database to estimate the incidence and prevalence of
      JORRP in 2006. Claims-based algorithms were designed to capture as many potential
      cases as possible. To improve the accuracy of the incidence and prevalence
      estimates, chart validation was performed to estimate the positive predictive
      value (PPV) of the claims-based algorithms. RESULTS: The overall PPV-adjusted
      incidence of JORRP in 2006 was 0.51 per 100,000 in Optum and 1.03 per 100,000 in
      the MarketScan Medicaid population. Peak incidence was observed among 0- to 4
      year-olds in both databases. The PPV-adjusted prevalence of JORRP in 2006 was
      1.45 and 2.93 per 100,000 in the Optum and MarketScan Medicaid cohorts,
      respectively. CONCLUSIONS: Although relatively uncommon, JORRP represents a
      disease with significant morbidity. The incidence and prevalence of JORRP in
      publicly insured children were consistently higher than those covered by private
      insurance plans, suggesting an increased burden of illness among those with lower
      socioeconomic status.

PMID- 24722384
TI  - Type of primary education is associated with condom use at sexual debut among
      Chilean adolescents.
AB  - BACKGROUND: Although condom use in adolescence is related to higher lifetime
      educational attainment, the association between primary education (from
      kindergarten to eighth grade) and adolescent sexual behavior is not well
      understood. This study examined the association between type of school in which
      primary education was completed-public, charter, or private-and condom use at
      sexual debut among Chilean adolescents. METHODS: Drawing on the 2009 Chilean
      National Youth Survey, a population-based sample of general community youth aged
      15 to 29 years, we conducted a study of the 4217 participants who reported onset
      of sexual activity during adolescence. Bivariate and multple logistic regression
      was used to examine the relationship between type of primary school attended
      (60.1% public, 30.3% charter, and 9.6% private) and condom use at sexual debut
      while controlling for sociodemographic characteristics and sexual behavior.
      RESULTS: Compared with students who completed their primary education in private
      or charter schools, students who completed their primary education in public
      schools had 1.85 (95% confidence interval, 1.12-3.04) and 1.67 (95% confidence
      interval, 1.26-2.23) higher odds, respectively, of not using condoms at sexual
      debut. Odds were similar for students living in urban settings, whereas there
      were too few students attending private schools in rural areas to allow
      meaningful estimates. CONCLUSIONS: Independent of household income, primary
      schooling is associated with sexual health behaviors among Chilean adolescents
      living in urban areas and can serve as a target for public health interventions
      designed to prevent sexually transmitted infections in adolescence.

PMID- 24722385
TI  - Violence, condom breakage, and HIV infection among female sex workers in Benin,
      West Africa.
AB  - OBJECTIVE: To examine the relationship between violence, condom breakage, and HIV
      prevalence among female sex workers (FSWs). METHODS: Data were obtained from the
      2012 cross-sectional integrated biological and behavioral survey conducted in
      Benin. Multivariable log-binomial regression was used to estimate the adjusted
      prevalence ratios of HIV infection and condom breakage in relation to violence
      toward FSWs. A score was created to examine the relationship between the number
      of violence types reported and HIV infection. RESULTS: Among the 981 women who
      provided a blood sample, HIV prevalence was 20.4%. During the last month, 17.2%,
      13.5%, and 33.5% of them had experienced physical, sexual, and psychological
      violence, respectively. In addition, 15.9% reported at least 1 condom breakage
      during the previous week. There was a significant association between all types
      of violence and HIV prevalence. The adjusted prevalence ratios of HIV were 1.45
      (95% confidence interval [95% CI], 1.05-2.00), 1.42 (95% CI, 1.02-1.98), and 1.41
      (95% CI, 1.08-1.41) among those who had ever experienced physical, sexual, and
      psychological violence, respectively. HIV prevalence increased with the violence
      score (P = 0.002, test for trend), and physical and sexual violence were
      independently associated with condom breakage (P = 0.010 and P = 0.003,
      respectively). CONCLUSIONS: The results show that violence is associated with a
      higher HIV prevalence among FSWs and that condom breakage is a potential mediator
      for this association. Longitudinal studies designed to analyze this relationship
      and specific interventions integrated to current HIV prevention strategies are
      needed to reduce the burden of violence among FSWs.

PMID- 24722386
TI  - Response to the modeling analysis by Katz et al. on the impact of replacing
      clinic-based HIV tests with home testing among men who have sex with men in
      Seattle.

PMID- 24722387
TI  - Response to the modeling analysis by Katz et al. on the impact of replacing
      clinic-based HIV tests with home testing among men who have sex with men in
      Seattle: authors' reply.

PMID- 24722388
TI  - A critical appraisal of risk models for predicting sexually transmitted
      infections.
AB  - BACKGROUND: Prediction rules have been proposed as alternatives to screening
      recommendations and have potential applications in sexual health decision making.
      To our knowledge, there has been no review undertaken providing a critical
      appraisal of existing prediction rules in sexual health contexts. This review
      aims to identify and characterize prediction rules developed and validated for
      sexually transmitted infection (STI) screening, describe the methodological
      issues essential to the suitability of derived models for clinical or public
      health application, and synthesize the literature on the performance of these
      models. METHODS: We searched MEDLINE (2003-2012) to identify studies that
      reported on models predicting STIs. We explored the methodological quality of the
      studies based on a 16-item quality assessment checklist. We also evaluated the
      studies based on data extracted on model discrimination, calibration,
      sensitivity, and testing efficiency. RESULTS: We identified 16 publications
      reporting on STI prediction rules. The most poorly addressed quality items were
      missing values, calibration measures, and variable definition. Overall, the
      performance of risk models as measured by discrimination (area under the receiver
      operating characteristic curve range, 0.64-0.88) and calibration was found to be
      generally good or satisfactory. Eight studies attained or were close to attaining
      the performance benchmark of testing less than 60% of the target population to
      achieve 90% sensitivity. The 2 risk models that were externally validated
      displayed adequate discrimination in new settings. CONCLUSIONS: Although we
      identified several well-performing STI risk prediction rules, few have been
      validated. Future developments in the use of prediction rules should address
      their clinical consequence, comparative usefulness, external validity, and
      implementation impact.

PMID- 24722389
TI  - Use of prediction rules in control of sexually transmitted infections: challenges
      and chances.

PMID- 24722390
TI  - Identifying syphilis risk networks through venue attendance in San Francisco.
AB  - BACKGROUND: Prioritizing interventions for patients with syphilis who are part of
      large or interconnected sexual networks may be high yield for partner services,
      and identifying venues named by patients with syphilis who report high numbers of
      partners may help identify such networks. In this analysis, we explore
      differences between interviewed patients with early syphilis regarding where they
      met sex partners. METHODS: With a cross-sectional design, we examined the
      distribution of total reported sex partners from male index patients with early
      syphilis interviewed through the San Francisco Department of Public Health
      partner services program and the self-reported venues named as places they met
      sex partners. Based on the median number of total partners among male cases of
      syphilis who named each venue, we categorized venues into 3 levels of partner
      frequency: high (>15 partners reported), medium (6-15 partners reported), and low
      (<6 partners reported). Interviewed patients with early syphilis were then
      classified into these venue categories, and sociodemographic and risk behaviors
      from electronic medical records and interviews were compared using chi tests.
      RESULTS: In 2011, 433 male patients with early syphilis named 32 venues. One
      hundred forty-three (32.3%) patients were categorized as high, 226 (51.0%) as
      medium, and 74 (16.7%) as low partner frequency venue users. Patients with early
      syphilis who reported meeting partners at high partner frequency venues were
      generally older, more likely to be white, have a previous syphilis infection, use
      methamphetamines in the previous year, and be HIV infected (all P < 0.05)
      compared with those who reported meeting partners at medium-frequency and low
      frequency venues. CONCLUSIONS: Venues where partners are met may be an
      appropriate proxy for network membership. Targeting additional resources,
      outreach, and services to clients who attend high-frequency venues may have a
      positive impact on syphilis prevention efforts.

PMID- 24722391
TI  - Variation in adherence to the treatment guidelines for Neisseria gonorrhoeae by
      clinical practice setting, California, 2009 to 2011.
AB  - BACKGROUND: Declining susceptibility of Neisseria gonorrhoeae to available
      antimicrobial agents has prompted repeated updates of the Centers for Disease
      Control and Prevention (CDC) treatment guidelines. The only regimen currently
      recommended as first-line treatment is dual therapy consisting of an
      intramuscular dose of ceftriaxone together with azithromycin or doxycycline. The
      objective of this analysis is to identify how adherence to the CDC guidelines
      varies by clinical practice setting. METHODS: A geographically representative
      random sample of N. gonorrhoeae cases reported from 2009 to 2011 was analyzed.
      Weighted generalized linear models were fit to calculate cumulative incidence
      ratios for receipt of non-recommended treatment regimen in relation to clinical
      practice setting, adjusted for age, race, and whether or not the participant was
      a man who has sex with men. RESULTS: Data from 3178 participants were available
      for analysis. Overall, 14.9% (weighted) of participants received non-recommended
      treatment. Among participants with gonorrhea identified by surveillance data as
      having received non-recommended treatment, the largest proportions were treated
      at private physicians' offices or health maintenance organizations (34.7% of
      participants receiving non-recommended treatment), family planning facilities
      (22.3%), and emergency departments/urgent care centers (12.8%). CONCLUSIONS:
      Barriers to adherence to the CDC treatment guidelines for gonorrhea seem to be
      experienced in a variety of clinical practice settings. Despite only moderate
      rates of nonadherence, interventions targeting private physicians/health
      maintenance organizations and family planning facilities may produce the largest
      absolute reductions in guideline-discordant treatment.

PMID- 24722392
TI  - The effect of multiple rounds of mass drug administration on the association
      between ocular Chlamydia trachomatis infection and follicular trachoma in
      preschool-aged children.
AB  - PURPOSE: To examine the relationship between ocular Chlamydia trachomatis
      infection and follicular trachoma (TF) in children prior to and following
      multiple rounds of annual mass drug administration (MDA) with azithromycin.
      METHODOLOGY/PRINCIPAL FINDINGS: Thirty-two communities with endemic trachoma in
      Kongwa District, Tanzania, were offered annual MDA as part of a district-wide
      trachoma control program. Presence of ocular C. trachomatis infection and TF were
      assessed in 3,200 randomly sampled children aged five years and younger, who were
      examined prior to each MDA. Infection was detected using the Amplicor CT/NG assay
      and TF was identified by clinical examination using the World Health Organization
      (WHO) simplified grading system. The association between chlamydial infection and
      TF in children was evaluated at baseline prior to any treatment, and 12 months
      after each of three annual rounds of mass treatment. Factors associated with
      infection were examined using generalized estimating equation models. At
      baseline, the overall prevalence of chlamydial infection and TF was 22% and 31%,
      respectively. Among children with clinical signs of TF, the proportion of those
      with infection was 49% prior to treatment and declined to 30% after three MDAs.
      The odds of infection positivity among children with clinical signs of TF
      decreased by 26% (OR 0.74, 95% CI 0.65 to 0.84, p = <0.01) with each MDA, after
      adjusting for age. For children aged under one year, who did not receive
      treatment, the relationship was unchanged. CONCLUSIONS/SIGNIFICANCE: The
      association between ocular C. trachomatis infection and TF weakened in children
      with each MDA, as both infection and clinical disease prevalence declined.
      However, there was still a significant proportion of TF cases with infection
      after three rounds of MDA. New strategies are needed to assess this residual
      infection for optimal treatment distribution.

PMID- 24722394
TI  - Pharmacogenomics, lipid disorders, and treatment options.
AB  - Statins form the backbone of lipid-lowering therapy in the prevention of
      cardiovascular disease. Numerous studies have evaluated the effect of genomics on
      the clinical efficacy and adverse effects of statins. Several gene variants that
      can be linked to either the pharmacokinetics or pharmacodynamics of statins have
      been identified as potentially important, although there are some discrepant
      findings among studies. Effect sizes are modest for lipid-lowering efficacy and
      perhaps somewhat larger for risk of myopathy, although results are inconsistent.
      Pharmacogenomics of nonstatin lipid-lowering agents have not been evaluated to
      the same extent, given their relatively limited use, although there are some
      promising candidate genes for further study. Finally, with several new classes of
      lipid-lowering therapies soon becoming available, there may be a potential
      application for pharmacogenomics to identify patients ideally suited to receive
      or those who should avoid-specific medications. 

PMID- 24722393
TI  - Geneva cocktail for cytochrome p450 and P-glycoprotein activity assessment using
      dried blood spots.
AB  - The suitability of the capillary dried blood spot (DBS) sampling method was
      assessed for simultaneous phenotyping of cytochrome P450 (CYP) enzymes and P
      glycoprotein (P-gp) using a cocktail approach. Ten volunteers received an oral
      cocktail capsule containing low doses of the probes bupropion (CYP2B6),
      flurbiprofen (CYP2C9), omeprazole (CYP2C19), dextromethorphan (CYP2D6), midazolam
      (CYP3A), and fexofenadine (P-gp) with coffee/Coke (CYP1A2) on four occasions.
      They received the cocktail alone (session 1), and with the CYP inhibitors
      fluvoxamine and voriconazole (session 2) and quinidine (session 3). In session 4,
      subjects received the cocktail after a 7-day pretreatment with the inducer
      rifampicin. The concentrations of probes/metabolites were determined in DBS and
      plasma using a single liquid chromatography-tandem mass spectrometry method. The
      pharmacokinetic profiles of the drugs were comparable in DBS and plasma.
      Important modulation of CYP and P-gp activities was observed in the presence of
      inhibitors and the inducer. Minimally invasive one- and three-point (at 2, 3, and
      6 h) DBS-sampling methods were found to reliably reflect CYP and P-gp activities
      at each session.

PMID- 24722395
TI  - Investigating the role of superdiffusive currents in laser induced
      demagnetization of ferromagnets with nanoscale magnetic domains.
AB  - Understanding the loss of magnetic order and the microscopic mechanisms involved
      in laser induced magnetization dynamics is one of the most challenging topics in
      today's magnetism research. While scattering between spins, phonons, magnons and
      electrons have been proposed as sources for dissipation of spin angular momentum,
      ultrafast spin dependent transport of hot electrons has been pointed out as a
      potential candidate to explain ultrafast demagnetization without resorting to any
      spin dissipation channel. Here we use time resolved magneto-optical Kerr
      measurements to extract the influence of spin dependent transport on the
      demagnetization dynamics taking place in magnetic samples with alternating
      domains with opposite magnetization directions. We unambiguously show that
      whatever the sample magnetic configuration, the demagnetization takes place
      during the same time, demonstrating that hot electrons spin dependent transfer
      between neighboring domains does not alter the ultrafast magnetization dynamics
      in our systems with perpendicular anisotropy and 140 nm domain sizes.

PMID- 24722396
TI  - Partial migration and transient coexistence of migrants and residents in animal
      populations.
AB  - Partial migration, whereby a proportion of the population migrates, is common
      across the animal kingdom. Much of the focus in the literature has been on trying
      to explain the underlying mechanisms for the coexistence of migrants and
      residents. In addition, there has been an increasing number of reports on the
      prevalence and frequency of partially migratory populations. One possible
      explanation for the occurrence of partial migration, which has received no
      attention in the literature, is that of 'transient coexistence' during the
      invasion phase of a superior behaviour. In this study we develop a theoretical
      basis for explaining partial migration as a transient coexistence and derive a
      method to predict the frequency of residents and migrants in partially migrating
      populations. This method is useful to predict the frequencies of migrants and
      residents in a small set of populations as a complementing hypothesis to 'an
      Evolutionary Stable Strategy (ESS)'. We use the logistic growth equation to
      derive a formula for predicting the frequencies of residents and migrants. We
      also use simulations and empirical data from white perch (Morone americana),
      moose (Alces alces) and red deer (Cervus elaphus) to demonstrate our approach. We
      show that the probability of detecting partial migration due to transient
      coexistence depends upon a minimum number of tracked or marked individuals for a
      given number of populations. Our approach provides a starting point in searching
      for explanations to the observed frequencies, by contrasting the observed pattern
      with both the predicted transient and the uniform random pattern. Aggregating
      such information on observed patterns (proportions of migrants and residents) may
      eventually lead to the development of a quantitative theory for the equilibrium
      (ESS) populations as well. 

PMID- 24722397
TI  - Spike-threshold adaptation predicted by membrane potential dynamics in vivo.
AB  - Neurons encode information in sequences of spikes, which are triggered when their
      membrane potential crosses a threshold. In vivo, the spiking threshold displays
      large variability suggesting that threshold dynamics have a profound influence on
      how the combined input of a neuron is encoded in the spiking. Threshold
      variability could be explained by adaptation to the membrane potential. However,
      it could also be the case that most threshold variability reflects noise and
      processes other than threshold adaptation. Here, we investigated threshold
      variation in auditory neurons responses recorded in vivo in barn owls. We found
      that spike threshold is quantitatively predicted by a model in which the
      threshold adapts, tracking the membrane potential at a short timescale. As a
      result, in these neurons, slow voltage fluctuations do not contribute to spiking
      because they are filtered by threshold adaptation. More importantly, these
      neurons can only respond to input spikes arriving together on a millisecond
      timescale. These results demonstrate that fast adaptation to the membrane
      potential captures spike threshold variability in vivo. 

PMID- 24722399
TI  - A multi-site evaluation of innovative approaches to increase tuberculosis case
      notification: summary results.
AB  - BACKGROUND: Globally, TB notifications have stagnated since 2007, and sputum
      smear positive notifications have been declining despite policies to improve case
      detection. We evaluate results of 28 interventions focused on improving TB case
      detection. METHODS: We measured additional sputum smear positive cases treated,
      defined as the intervention area's increase in case notification during the
      project compared to the previous year. Projects were encouraged to select control
      areas and collect historical notification data. We used time series negative
      binomial regression for over-dispersed cross-sectional data accounting for fixed
      and random effects to test the individual projects' effects on TB notification
      while controlling for trend and control populations. RESULTS: Twenty-eight
      projects, 19 with control populations, completed at least four quarters of case
      finding activities, covering a population of 89.2 million. Among all projects
      sputum smear positive (SS+) TB notifications increased 24.9% and annualized
      notification rates increased from 69.1 to 86.2/100,000 (p = 0.0209) during
      interventions. Among the 19 projects with control populations, SS+TB case
      notifications increased 36.9% increase while in the control populations a 3.6%
      decrease was observed. Fourteen (74%) of the 19 projects' SS+TB notification
      rates in intervention areas increased from the baseline to intervention period
      when controlling for historical trends and notifications in control areas.
      CONCLUSIONS: Interventions were associated with large increases in TB
      notifications across many settings, using an array of interventions. Many people
      with TB are not reached using current approaches. Different methods and
      interventions tailored to local realities are urgently needed.

PMID- 24722398
TI  - Progressive accumulation of activated ERK2 within highly stable ORF45-containing
      nuclear complexes promotes lytic gammaherpesvirus infection.
AB  - De novo infection with the gammaherpesvirus Rhesus monkey rhadinovirus (RRV), a
      close homolog of the human oncogenic pathogen, Kaposi's sarcoma-associated
      herpesvirus (KSHV), led to persistent activation of the MEK/ERK pathway and
      increasing nuclear accumulation of pERK2 complexed with the RRV protein, ORF45
      (R45) and cellular RSK. We have previously shown that both lytic gene expression
      and virion production are dependent on the activation of ERK [1]. Using confocal
      microscopy, sequential pull-down assays and FRET analyses, we have demonstrated
      that pERK2-R45-RSK2 complexes were restricted to the nucleus but that the
      activated ERK retained its ability to phosphorylate nuclear substrates throughout
      infection. Furthermore, even with pharmacologic inhibition of MEK beginning at 48
      h p.i., pERK2 but not pERK1, remained elevated for at least 10 h, showing first
      order decay and a half-life of nearly 3 hours. Transfection of rhesus fibroblasts
      with R45 alone also led to the accumulation of nuclear pERK2 and addition of
      exogenous RSK augmented this effect. However, knock down of RSK during bona fide
      RRV infection had little to no effect on pERK2 accumulation or virion production.
      The cytoplasmic pools of pERK showed no co-localization with either RSK or R45
      but activation of pERK downstream targets in this compartment was evident
      throughout infection. Together, these observations suggest a model in which R45
      interacts with pERK2 to promote its nuclear accumulation, thereby promoting lytic
      viral gene expression while also preserving persistent and robust activation of
      both nuclear and cytoplasmic ERK targets. 

PMID- 24722401
TI  - A reentrant phenomenon in magnetic and dielectric properties of Dy2BaNiO5 and an
      intriguing influence of external magnetic field.
AB  - We report that the spin-chain compound Dy2BaNiO5, recently proven by us to
      exhibit magnetoelectric coupling below its Neel temperature (TN) of 58 K,
      exhibits strong frequency-dependent behavior in ac magnetic susceptibility and
      complex dielectric properties at low temperatures (<10 K), mimicking the
      'reentrant' multiglass phenomenon. Such a behavior is not known among undoped
      compounds. A new finding in the field of multiferroics is that the characteristic
      magnetic feature at low temperatures moves towards higher temperatures in the
      presence of a magnetic field (H), whereas the corresponding dielectric feature
      shifts towards lower temperatures with H, unlike the situation near TN. This
      observation indicates that the alignment of spins by external magnetic fields
      tends to inhibit glassy-like slow electric-dipole dynamics, at least in this
      system, possibly arising from peculiarities in the magnetic structure. 

PMID- 24722400
TI  - Diffuse large B-cell lymphoma with combined TP53 mutation and MIR34A methylation:
      Another "double hit" lymphoma with very poor outcome?
AB  - MiR34A, B and C have been implicated in lymphomagenesis, but information on their
      role in normal CD19+ B-cells (PBL-B) and de novo diffuse large B-cell lymphoma
      (DLBCL) is limited. We show that in normal and activated B-cells miR34A-5p plays
      a dominant role compared to other miR34 family members. Only miR34A-5p is
      expressed in PBL-B, and significantly induced in activated B-cells and reactive
      lymph nodes. In PBL-B, the MIR34A and MIR34B/C promoters are unmethylated, but
      the latter shows enrichment for the H3K4me3/H3K27me3 silencing mark. Nine de novo
      DLBCL cases (n=150) carry both TP53 mutation and MIR34A methylation ("double
      hit") and these patients have an exceedingly poor prognosis with a median
      survival of 9.4 months (P<0.0001), while neither TP53 mutation, MIR34A or
      MIR34B/C promoter methylation alone ("single hit") influence on survival. The
      TP53/MIR34A "double-hit" is an independent negative prognostic factor for
      survival (P=0.0002). In 2 DLBCL-cell lines with both TP53 mutation and promoter
      methylation of MIR34A, miR34A-5p is upregulated by 5-aza-2'deoxycytidine. Thus,
      the TP53/MIR34A "double hit" characterizes a very aggressive subgroup of DLBCL,
      which may be treatable with epigenetic therapy prior to or in combination with
      conventional immunochemotherapy. 

PMID- 24722402
TI  - A 3-D in vitro co-culture model of mammary gland involution.
AB  - Involution is a process whereby the mammary gland undergoes extensive tissue
      remodelling involving exquisitely coordinated cell death, extracellular matrix
      degradation and adipose tissue regeneration following the weaning of offspring.
      These processes are mediated in part through Jak/Stat signalling pathways, which
      can be deregulated in breast cancer. Synthetic in vitro analogues of the breast
      could become important tools for studying tumorigenic processes, or as
      personalized drug discovery platforms and predictors of therapeutic response.
      Ideally, such models should support 3D neo-tissue formation, so as to
      recapitulate physiological organ function, and be compatible with high-throughput
      screening methodologies. We have combined cell lines of epithelial, stromal and
      immunological origin within engineered porous collagen/hyaluronic acid matrices,
      demonstrating 3D-specific molecular signatures. Furthermore seeded cells form
      mammary-like branched tissues, with lobuloalveolar structures that undergo
      inducible involution phenotypes reminiscent of the native gland under
      hormonal/cytokine regulation. We confirm that autophagy is mediated within
      differentiated mammary epithelial cells in a Stat-dependent manner at early time
      points following the removal of a prolactin stimulus (H/WD). In addition,
      epithelial cells express markers of an M2 macrophage lineage under H/WD, a
      process that is attenuated with the introduction of the monocyte/macrophage cell
      line RAW 264.7. Thus, such 3D models are suitable platforms for studying cell
      cell interactions and cell death mechanisms in relation to cancer. 

PMID- 24722403
TI  - Obtaining genomes from uncultivated environmental microorganisms using FACS-based
      single-cell genomics.
AB  - Single-cell genomics is a powerful tool for exploring the genetic makeup of
      environmental microorganisms, the vast majority of which are difficult, if not
      impossible, to cultivate with current approaches. Here we present a comprehensive
      protocol for obtaining genomes from uncultivated environmental microbes via high
      throughput single-cell isolation by FACS. The protocol encompasses the
      preservation and pretreatment of differing environmental samples, followed by the
      physical separation, lysis, whole-genome amplification and 16S rRNA-based
      identification of individual bacterial and archaeal cells. The described
      procedure can be performed with standard molecular biology equipment and a FACS
      machine. It takes <12 h of bench time over a 4-d time period, and it generates up
      to 1 MUg of genomic DNA from an individual microbial cell, which is suitable for
      downstream applications such as PCR amplification and shotgun sequencing. The
      completeness of the recovered genomes varies, with an average of ~50%. 

PMID- 24722404
TI  - Quantifying the forces guiding microbial cell adhesion using single-cell force
      spectroscopy.
AB  - During the past decades, several methods (e.g., electron microscopy, flow chamber
      experiments, surface chemical analysis, surface charge and surface hydrophobicity
      measurements) have been developed to investigate the mechanisms controlling the
      adhesion of microbial cells to other cells and to various other substrates.
      However, none of the traditional approaches are capable of looking at adhesion
      forces at the single-cell level. In recent years, atomic force microscopy (AFM)
      has been instrumental in measuring the forces driving microbial adhesion on a
      single-cell basis. The method, known as single-cell force spectroscopy (SCFS),
      consists of immobilizing a single living cell on an AFM cantilever and measuring
      the interaction forces between the cellular probe and a solid substrate or
      another cell. Here we present SCFS protocols that we have developed for
      quantifying the cell adhesion forces of medically important microbes. Although we
      focus mainly on the probiotic bacterium Lactobacillus plantarum, we also show
      that our procedures are applicable to pathogens, such as the bacterium
      Staphylococcus epidermidis and the yeast Candida albicans. For well-trained
      microscopists, the entire protocol can be mastered in 1 week. 

PMID- 24722405
TI  - Characterization of ancient and modern genomes by SNP detection and phylogenomic
      and metagenomic analysis using PALEOMIX.
AB  - Next-generation sequencing technologies have revolutionized the field of
      paleogenomics, allowing the reconstruction of complete ancient genomes and their
      comparison with modern references. However, this requires the processing of vast
      amounts of data and involves a large number of steps that use a variety of
      computational tools. Here we present PALEOMIX
      (http://geogenetics.ku.dk/publications/paleomix), a flexible and user-friendly
      pipeline applicable to both modern and ancient genomes, which largely automates
      the in silico analyses behind whole-genome resequencing. Starting with next
      generation sequencing reads, PALEOMIX carries out adapter removal, mapping
      against reference genomes, PCR duplicate removal, characterization of and
      compensation for postmortem damage, SNP calling and maximum-likelihood
      phylogenomic inference, and it profiles the metagenomic contents of the samples.
      As such, PALEOMIX allows for a series of potential applications in paleogenomics,
      comparative genomics and metagenomics. Applying the PALEOMIX pipeline to the
      three ancient and seven modern Phytophthora infestans genomes as described here
      takes 5 d using a 16-core server. 

PMID- 24722406
TI  - 3D live fluorescence imaging of cellular dynamics using Bessel beam plane
      illumination microscopy.
AB  - 3D live imaging is important for a better understanding of biological processes,
      but it is challenging with current techniques such as spinning-disk confocal
      microscopy. Bessel beam plane illumination microscopy allows high-speed 3D live
      fluorescence imaging of living cellular and multicellular specimens with nearly
      isotropic spatial resolution, low photobleaching and low photodamage. Unlike
      conventional fluorescence imaging techniques that usually have a unique operation
      mode, Bessel plane illumination has several modes that offer different
      performance with different imaging metrics. To achieve optimal results from this
      technique, the appropriate operation mode needs to be selected and the
      experimental setting must be optimized for the specific application and
      associated sample properties. Here we explain the fundamental working principles
      of this technique, discuss the pros and cons of each operational mode and show
      through examples how to optimize experimental parameters. We also describe the
      procedures needed to construct, align and operate a Bessel beam plane
      illumination microscope by using our previously reported system as an example,
      and we list the necessary equipment to build such a microscope. Assuming all
      components are readily available, it would take a person skilled in optical
      instrumentation ~1 month to assemble and operate a microscope according to this
      protocol. 

PMID- 24722409
TI  - Microbial growth and carbon use efficiency in the rhizosphere and root-free soil.
AB  - Plant-microbial interactions alter C and N balance in the rhizosphere and affect
      the microbial carbon use efficiency (CUE)-the fundamental characteristic of
      microbial metabolism. Estimation of CUE in microbial hotspots with high dynamics
      of activity and changes of microbial physiological state from dormancy to
      activity is a challenge in soil microbiology. We analyzed respiratory activity,
      microbial DNA content and CUE by manipulation the C and nutrients availability in
      the soil under Beta vulgaris. All measurements were done in root-free and
      rhizosphere soil under steady-state conditions and during microbial growth
      induced by addition of glucose. Microorganisms in the rhizosphere and root-free
      soil differed in their CUE dynamics due to varying time delays between
      respiration burst and DNA increase. Constant CUE in an exponentially-growing
      microbial community in rhizosphere demonstrated the balanced growth. In contrast,
      the CUE in the root-free soil increased more than three times at the end of
      exponential growth and was 1.5 times higher than in the rhizosphere. Plants alter
      the dynamics of microbial CUE by balancing the catabolic and anabolic processes,
      which were decoupled in the root-free soil. The effects of N and C availability
      on CUE in rhizosphere and root-free soil are discussed. 

PMID- 24722410
TI  - Inhibiting Na+/K+ ATPase can impair mitochondrial energetics and induce abnormal
      Ca2+ cycling and automaticity in guinea pig cardiomyocytes.
AB  - Cardiac glycosides have been used for the treatment of heart failure because of
      their capabilities of inhibiting Na+/K+ ATPase (NKA), which raises [Na+]i and
      attenuates Ca2+ extrusion via the Na+/Ca2+ exchanger (NCX), causing [Ca2+]i
      elevation. The resulting [Ca2+]i accumulation further enhances Ca2+-induced Ca2+
      release, generating the positive inotropic effect. However, cardiac glycosides
      have some toxic and side effects such as arrhythmogenesis, confining their
      extensive clinical applications. The mechanisms underlying the proarrhythmic
      effect of glycosides are not fully understood. Here we investigated the
      mechanisms by which glycosides could cause cardiac arrhythmias via impairing
      mitochondrial energetics using an integrative computational cardiomyocyte model.
      In the simulations, the effect of glycosides was mimicked by blocking NKA
      activity. Results showed that inhibiting NKA not only impaired mitochondrial Ca2+
      retention (thus suppressed reactive oxygen species (ROS) scavenging) but also
      enhanced oxidative phosphorylation (thus increased ROS production) during the
      transition of increasing workload, causing oxidative stress. Moreover, concurrent
      blocking of mitochondrial Na+/Ca2+ exchanger, but not enhancing of Ca2+
      uniporter, alleviated the adverse effects of NKA inhibition. Intriguingly, NKA
      inhibition elicited Ca2+ transient and action potential alternans under more
      stressed conditions such as severe ATP depletion, augmenting its proarrhythmic
      effect. This computational study provides new insights into the mechanisms
      underlying cardiac glycoside-induced arrhythmogenesis. The findings suggest that
      targeting both ion handling and mitochondria could be a very promising strategy
      to develop new glycoside-based therapies in the treatment of heart failure. 

PMID- 24722411
TI  - Physical activity and excess weight in pregnancy have independent and unique
      effects on delivery and perinatal outcomes.
AB  - BACKGROUND: This study examines the effect of low daily physical activity levels
      and overweight/obesity in pregnancy on delivery and perinatal outcomes. METHODS:
      A prospective cohort study combining manually collected postnatal notes with
      anonymised data linkage. A total of 466 women sampled from the Growing Up in
      Wales: Environments for Healthy Living study. Women completed a questionnaire and
      were included in the study if they had an available Body mass index (BMI)
      (collected at 12 weeks gestation from antenatal records) and/or a physical
      activity score during pregnancy (7-day Actigraph reading). The full statistical
      model included the following potential confounding factors: maternal age, parity
      and smoking status. Main outcome measures included induction rates, duration of
      labour, mode of delivery, infant health and duration of hospital stay. FINDINGS:
      Mothers with lower physical activity levels were more likely to have an
      instrumental delivery (including forceps, ventouse and elective and emergency
      caesarean) in comparison to mothers with higher activity levels (adjusted
      OR:1.72(95%CI: 1.05 to 2.9)). Overweight/obese mothers were more likely to
      require an induction (adjusted OR:1.93 (95%CI 1.14 to 3.26), have a macrosomic
      baby (adjusted OR:1.96 (95%CI 1.08 to 3.56) and a longer hospital stay after
      delivery (adjusted OR:2.69 (95%CI 1.11 to 6.47). CONCLUSIONS: The type of
      delivery was associated with maternal physical activity level and not BMI.
      Perinatal outcomes (large for gestational age only) were determined by maternal
      BMI.

PMID- 24722412
TI  - Hemodynamics and function of resistance arteries in healthy persons and end stage
      renal disease patients.
AB  - INTRODUCTION: Cardiovascular disease is the leading cause of death in patients
      with end stage renal disease (ESRD). The vasodilator mechanisms in small
      resistance arteries are in earlier studies shown to be reduced in patients with
      end stage renal disease. We studied whether endothelium dependent vasodilatation
      were diminished in ESRD patients and the interaction between the macro- and
      microcirculation. METHODS: Eleven patients with ESRD had prior to renal
      transplant or insertion of peritoneal dialysis catheter measured pulse wave
      velocity. During surgery, a subcutaneous fat biopsy was extracted. Resistance
      arteries were then dissected and mounted on a wire myograph for measurements of
      dilator response to increasing concentrations of acetylcholine after
      preconstriction with noradrenaline. Twelve healthy kidney donors served as
      controls. RESULTS: Systolic blood pressure was elevated in patients compared to
      the healthy controls; no difference in the concentration of asymmetric dimethyl
      arginine was seen. No significant difference in the endothelium dependent
      vasodilatation between patients and controls was found. Correlation of small
      artery properties showed an inverse relationship between diastolic blood pressure
      and nitric oxide dependent vasodilatation in controls. Pulse pressure was
      positively correlated to the total endothelial vasodilatation in patients. A
      negative association between S-phosphate and endothelial derived
      hyperpolarisation-like vasodilatation was seen in resistance arteries from
      controls. CONCLUSION: This study finds similar vasodilator properties in kidney
      patients and controls. However, correlations of pulse pressure and diastolic
      blood pressure with resistance artery function indicate compensating measures in
      the microcirculation during end stage renal disease.

PMID- 24722413
TI  - Mechanisms underlying Plk1 polo-box domain-mediated biological processes and
      their physiological significance.
AB  - Mammalian polo-like kinase 1 (Plk1) has been studied intensively as a key
      regulator of various cell cycle events that are critical for proper M-phase
      progression. The polobox domain (PBD) present in Plk1's C-terminal noncatalytic
      region has been shown to play a central role in targeting the N-terminal kinase
      domain of Plk1 to specific subcellular locations. Subsequent studies reveal that
      PBD binds to a phosphorylated motif generated by one of the two mechanisms-self
      priming by Plk1 itself or non-selfpriming by a Pro-directed kinase, such as Cdc2.
      Here, we comparatively review the differences in the biochemical steps of these
      mechanisms and discuss their physiological significance. Considering the diverse
      functions of Plk1 during the cell cycle, a better understanding of how the
      catalytic activity of Plk1 functions in concert with its cisacting PBD and how
      this coordinated process is intricately regulated to promote Plk1 functions will
      be important for providing new insights into different mechanisms underlying
      various Plk1-mediated biological events that occur at the multiple stages of the
      cell cycle. 

PMID- 24722414
TI  - Down-regulation of Sox11 is required for efficient osteogenic differentiation of
      adipose-derived stem cells.
AB  - Adipose-derived stem cells represent a type of mesenchymal stem cells with the
      attendant capacity to self-renew and differentiate into multiple cell lineages.
      We have performed a microarray-based gene expression profiling of osteogenic
      differentiation and found that the transcription factor Sox11 is down-regulated
      during the process. Functional assays demonstrate that down-regulation of Sox11
      is required for an efficient differentiation. Furthermore, results from forced
      expression of constitutively-active and dominant-negative derivatives of Sox11
      indicate that Sox11 functions as a transcriptional activator in inhibiting
      osteogenesis. Sox11 thus represents a novel regulator of osteogenesis whose
      expression and activity can be potentially manipulated for controlled
      differentiation. 

PMID- 24722415
TI  - Upregulation of dendritic arborization by N-acetyl-D-glucosamine kinase is not
      dependent on its kinase activity.
AB  - N-acetylglucosamine kinase (GlcNAc kinase or NAGK; EC 2.7.1.59) is highly
      expressed and plays a critical role in the development of dendrites in brain
      neurons. In this study, the authors conducted structure-function analysis to
      verify the previously proposed 3D model structure of GlcNAc/ ATP-bound NAGK.
      Three point NAGK mutants with different substrate binding capacities and reaction
      velocities were produced. Wild-type (WT) NAGK showed strong substrate preference
      for GlcNAc. Conversion of Cys143, which does not make direct hydrogen bonds with
      GlcNAc, to Ser (i.e., C143S) had the least affect on the enzymatic activity of
      NAGK. Conversion of Asn36, which plays a role in domain closure by making a
      hydrogen bond with GlcNAc, to Ala (i.e., N36A) mildly reduced NAGK enzyme
      activity. Conversion of Asp107, which makes hydrogen bonds with GlcNAc and would
      act as a proton acceptor during nucleophilic attack on the gamma-phosphate of
      ATP, to Ala (i.e., D107A), caused a total loss in enzyme activity. The
      overexpression of EGFP-tagged WT or any of the mutant NAGKs in rat hippocampal
      neurons (DIV 5-9) increased dendritic architectural complexity. Finally, the
      overexpression of the small, but not of the large, domain of NAGK resulted in
      dendrite degeneration. Our data show the effect of structure on the functional
      aspects of NAGK, and in particular, that the small domain of NAGK, and not its
      NAGK kinase activity, plays a critical role in the upregulation of
      dendritogenesis. 

PMID- 24722416
TI  - Mycobacterium ulcerans fails to infect through skin abrasions in a guinea pig
      infection model: implications for transmission.
AB  - Transmission of M. ulcerans, the etiological agent of Buruli ulcer, from the
      environment to humans remains an enigma despite decades of research. Major
      transmission hypotheses propose 1) that M. ulcerans is acquired through an insect
      bite or 2) that bacteria enter an existing wound through exposure to a
      contaminated environment. In studies reported here, a guinea pig infection model
      was developed to determine whether Buruli ulcer could be produced through passive
      inoculation of M. ulcerans onto a superficial abrasion. The choice of an abrasion
      model was based on the fact that most bacterial pathogens infecting the skin are
      able to infect an open lesion, and that abrasions are extremely common in
      children. Our studies show that after a 90d infection period, an ulcer was
      present at intra-dermal injection sites of all seven animals infected, whereas
      topical application of M. ulcerans failed to establish an infection.
      Mycobacterium ulcerans was cultured from all injection sites whereas infected
      abrasion sites healed and were culture negative. A 14d experiment was conducted
      to determine how long organisms persisted after inoculation. Mycobacterium
      ulcerans was isolated from abrasions at one hour and 24 hours post infection, but
      cultures from later time points were negative. Abrasion sites were qPCR positive
      up to seven days post infection, but negative at later timepoints. In contrast,
      M. ulcerans DNA was detected at intra-dermal injection sites throughout the
      study. M. ulcerans was cultured from injection sites at each time point. These
      results suggest that injection of M. ulcerans into the skin greatly facilitates
      infection and lends support for the role of an invertebrate vector or other route
      of entry such as a puncture wound or deep laceration where bacteria would be
      contained within the lesion. Infection through passive inoculation into an
      existing abrasion appears a less likely route of entry. 

PMID- 24722417
TI  - Purkinje cell compartmentation in the cerebellum of the lysosomal Acid
      phosphatase 2 mutant mouse (nax - naked-ataxia mutant mouse).
AB  - The Acp2 gene encodes the beta subunit of lysosomal acid phosphatase, which is an
      isoenzyme that hydrolyzes orthophosphoric monoesters. In mice, a spontaneous
      mutation in Acp2 results in severe cerebellar defects. These include a reduced
      size, abnormal lobulation, and an apparent anterior cerebellar disorder with an
      absent or hypoplastic vermis. Based on differential gene expression in the
      cerebellum, the mouse cerebellar cortex can normally be compartmentalized
      anteroposteriorly into four transverse zones and mediolaterally into parasagittal
      stripes. In this study, immunohistochemistry was performed using various Purkinje
      cell compartmentation markers to examine their expression patterns in the Acp2
      mutant. Despite the abnormal lobulation and anterior cerebellar defects, zebrin
      II and PLCbeta4 showed similar expression patterns in the nax mutant and wild
      type cerebellum. However, fewer stripes were found in the anterior zone of the
      nax mutant, which could be due to a lack of Purkinje cells or altered expression
      of the stripe markers. HSP25 expression was uniform in the central zone of the
      nax mutant cerebellum at around postnatal day (P) 18-19, suggesting that HSP25
      immunonegative Purkinje cells are absent or delayed in stripe pattern expression
      compared to the wild type. HSP25 expression became heterogeneous around P22-23,
      with twice the number of parasagittal stripes in the nax mutant compared to the
      wild type. Aside from reduced size and cortical disorganization, both the
      posterior zone and nodular zone in the nax mutant appeared less abnormal than the
      rest of the cerebellum. From these results, it is evident that the anterior zone
      of the nax mutant cerebellum is the most severely affected, and this extends
      beyond the primary fissure into the rostral central zone/vermis. This suggests
      that ACP2 has critical roles in the development of the anterior cerebellum and it
      may regulate anterior and central zone compartmentation. 

PMID- 24722418
TI  - Melanoma transition is frequently accompanied by a loss of cytoglobin expression
      in melanocytes: a novel expression site of cytoglobin.
AB  - The tissue distribution and function of hemoglobin or myoglobin are well known;
      however, a newly found cytoglobin (CYGB), which also belongs to the globin
      family, remains to be characterized. To assess its expression in human
      malignancies, we sought to screen a number of cell lines originated from many
      tissues using northern blotting and real time PCR techniques. Unexpectedly, we
      found that several, but not all, melanoma cell lines expressed CYGB mRNA and
      protein at much higher levels than cells of other origins. Melanocytes, the
      primary origin of melanoma, also expressed CYGB at a high level. To verify these
      observations, immunostaining and immunoblotting using anti-CYGB antibody were
      also performed. Bisulfite-modified genomic sequencing revealed that several
      melanoma cell lines that abrogated CYGB expression were found to be
      epigenetically regulated by hypermethylation in the promoter region of CYGB gene.
      The RNA interference-mediated knockdown of the CYGB transcript in CYGB expression
      positive melanoma cell lines resulted in increased proliferation in vitro and in
      vivo. Flow cytometric analysis using 2'-, 7'-dichlorofluorescein diacetate (DCFH
      DA), an indicator of reactive oxygen species (ROS), revealed that the cellular
      ROS level may be involved in the proliferative effect of CYGB. Thus, CYGB appears
      to play a tumor suppressive role as a ROS regulator, and its epigenetic
      silencing, as observed in CYGB expression-negative melanoma cell lines, might
      function as an alternative pathway in the melanocyte-to-melanoma transition.

PMID- 24722419
TI  - Coxsackievirus-induced miR-21 disrupts cardiomyocyte interactions via the
      downregulation of intercalated disk components.
AB  - Intercalated disks (ICDs) are substantial connections maintaining cardiac
      structures and mediating signal communications among cardiomyocytes. Deficiency
      in ICD components such as desmosomes, fascia adherens and gap junctions leads to
      heart dysfunction. Coxsackievirus B3 (CVB3) infection induces cardiac failure but
      its pathogenic effect on ICDs is unclear. Here we show that CVB3-induced miR-21
      expression affects ICD structure, i.e., upregulated miR-21 targets YOD1, a
      deubiquitinating enzyme, to enhance the K48-linked ubiquitination and degradation
      of desmin, resulting in disruption of desmosomes. Inhibition of miR-21 preserves
      desmin during CVB3 infection. Treatment with proteasome inhibitors blocks miR-21
      mediated desmin degradation. Transfection of miR-21 or knockdown of YOD1 triggers
      co-localization of desmin with proteasomes. We also identified K108 and K406 as
      important sites for desmin ubiquintination and degradation. In addition, miR-21
      directly targets vinculin, leading to disturbed fascia adherens evidenced by the
      suppression and disorientation of pan-cadherin and alpha-E-catenin proteins, two
      fascia adherens-components. Our findings suggest a new mechanism of miR-21 in
      modulating cell-cell interactions of cardiomyocytes during CVB3 infection. 

PMID- 24722420
TI  - The spatial resolution of epidemic peaks.
AB  - The emergence of novel respiratory pathogens can challenge the capacity of key
      health care resources, such as intensive care units, that are constrained to
      serve only specific geographical populations. An ability to predict the magnitude
      and timing of peak incidence at the scale of a single large population would help
      to accurately assess the value of interventions designed to reduce that peak.
      However, current disease-dynamic theory does not provide a clear understanding of
      the relationship between: epidemic trajectories at the scale of interest (e.g.
      city); population mobility; and higher resolution spatial effects (e.g.
      transmission within small neighbourhoods). Here, we used a spatially-explicit
      stochastic meta-population model of arbitrary spatial resolution to determine the
      effect of resolution on model-derived epidemic trajectories. We simulated an
      influenza-like pathogen spreading across theoretical and actual population
      densities and varied our assumptions about mobility using Latin-Hypercube
      sampling. Even though, by design, cumulative attack rates were the same for all
      resolutions and mobilities, peak incidences were different. Clear thresholds
      existed for all tested populations, such that models with resolutions lower than
      the threshold substantially overestimated population-wide peak incidence. The
      effect of resolution was most important in populations which were of lower
      density and lower mobility. With the expectation of accurate spatial incidence
      datasets in the near future, our objective was to provide a framework for how to
      use these data correctly in a spatial meta-population model. Our results suggest
      that there is a fundamental spatial resolution for any pathogen-population pair.
      If underlying interactions between pathogens and spatially heterogeneous
      populations are represented at this resolution or higher, accurate predictions of
      peak incidence for city-scale epidemics are feasible. 

PMID- 24722422
TI  - Positioning of APOBEC3G/F mutational hotspots in the human immunodeficiency virus
      genome favors reduced recognition by CD8+ T cells.
AB  - Due to constitutive expression in cells targeted by human immunodeficiency virus
      (HIV), and immediate mode of viral restriction upon HIV entry into the host cell,
      APOBEC3G (A3G) and APOBEC3F (A3F) have been considered primarily as agents of
      innate immunity. Recent bioinformatic and mouse model studies hint at the
      possibility that mutation of the HIV genome by these enzymes may also affect
      adaptive immunity but whether this occurs in HIV-infected individuals has not
      been examined. We evaluated whether APOBEC-mediated mutations within common HIV
      CD8+ T cell epitopes can potentially enhance or diminish activation of HIV
      specific CD8+ T cells from infected individuals. We compared ex vivo activation
      of CD8+ T lymphocytes from HIV-infected individuals by wild type HIV peptide
      epitopes and synthetic variants bearing simulated A3G/F-induced mutations by
      measuring interferon-gamma (IFN-gamma) production. We found that A3G/F-induced
      mutations consistently diminished HIV-specific CD8+ T cell responses against the
      common epitopes we tested. If this reflects a significant trend in vivo, then
      adaptation by HIV to enrich sequences that are favored for mutation by A3G/F
      (A3G/F hotspots) in portions of its genome that encode immunogenic CD8+ T cell
      epitopes would favor CTL escape. Indeed, we found the most frequently mutated A3G
      motif (CCC) is enriched up to 6-fold within viral genomic sequences encoding
      immunodominant CD8+ T cell epitopes in Gag, Pol and Nef. Within each gene, A3G/F
      hotspots are more abundant in sequences encoding epitopes that are commonly
      recognized due to their HLA restriction. Thus, in our system, mutations of the
      HIV genome, mimicking A3G/F activity, appeared to abrogate or severely reduce CTL
      recognition. We suggest that the physiological significance of this potential
      effect in facilitating CTL escape is echoed in the adaptation of the HIV genome
      to enrich A3G/F hotspots in sequences encoding CTL epitopes that are more
      immunogenic at the population level. 

PMID- 24722424
TI  - A simple, inexpensive method for preparing cell lysates suitable for downstream
      reverse transcription quantitative PCR.
AB  - Sample nucleic acid purification can often be rate-limiting for conventional
      quantitative PCR (qPCR) workflows. We recently developed high-throughput virus
      microneutralization assays using an endpoint assessment approach based on reverse
      transcription qPCR (RT-qPCR). The need for cumbersome RNA purification is
      circumvented in our assays by making use of a commercial reagent that can easily
      generate crude cell lysates amenable to direct analysis by one-step RT-qPCR. In
      the present study, we demonstrate that a simple buffer containing a non-ionic
      detergent can serve as an inexpensive alternative to commercially available
      reagents for the purpose of generating RT-qPCR-ready cell lysates from MDCK cells
      infected with influenza virus. We have found that addition of exogenous RNase
      inhibitor as a buffer component is not essential in order to maintain RNA
      integrity, even following stress at 37  degrees C incubation for 1-2 hours, in
      cell-lysate samples either freshly prepared or previously stored frozen at -80 
      degrees C.

PMID- 24722423
TI  - Therapeutic effect of Jinzhen oral liquid for hand foot and mouth disease: a
      randomized, multi-center, double-blind, placebo-controlled trial.
AB  - BACKGROUND: No specific antiviral agent against hand foot and mouth disease
      (HFMD) is available for clinical practice today. OBJECTIVE: To evaluate the
      efficacy and safety of Jinzhen oral solution in treating uncomplicated HFMD.
      METHODS: In this randomized, double-blind, placebo-controlled trial, 399 children
      aged 1 to 7 years with laboratory confirmed HFMD were randomized to receive
      Jinzhen oral liquid or placebo 3 times daily for 7 days with a 3-day follow-up.
      The primary outcomes were time to the first disappearance of oral ulcers and
      vesicles on hand or foot and time to the first normalization of temperature
      (fever clearance). RESULTS: There were 199 children enrolling into the Jinzhen
      group including 79 with fever and 200 into the placebo group including 93 with
      fever. Jinzhen reduced the time to the first disappearance of oral ulcers and
      vesicles on hand or foot to 4.9 days (95% CI, 4.6 to 5.2 days), compared with 5.7
      days (95% CI, 5.4 to 6.0 days) in the placebo group (P = 0.0036). The median time
      of fever clearance was shorter in the 79 children who received Jinzhen (43.41
      hrs, 95% CI, 37.05 to 49.76) than that in the 93 children who received placebo
      (54.92 hrs, 95% CI, 48.16 to 61.68) (P = 0.0161). Moreover, Jinzhen reduced the
      risk of symptoms by 28.5% compared with placebo (HR, 0.7150, 95% CI, 0.5719 to
      0.8940, P = 0.0032). More importantly, treatment failure rate was significantly
      lower in the Jinzhen group (8.04%) compared with that in the placebo group
      (15.00%) (P = 0.0434). The incidence of serious adverse events did not differ
      significantly between the two groups (9 in Jinzhen group vs. 18 in placebo, P =
      0.075). CONCLUSIONS: Children with HFMD may benefit from Jinzhen oral liquid
      treatment as compared with placebo. TRIAL REGISTRATION: Chinese Clinical Trial
      Registry (http://www.chictr.org/en/) ChiCTR-TRC-10000937.

PMID- 24722425
TI  - On the validity of evolutionary models with site-specific parameters.
AB  - Evolutionary models that make use of site-specific parameters have recently been
      criticized on the grounds that parameter estimates obtained under such models can
      be unreliable and lack theoretical guarantees of convergence. We present a
      simulation study providing empirical evidence that a simple version of the models
      in question does exhibit sensible convergence behavior and that additional taxa,
      despite not being independent of each other, lead to improved parameter
      estimates. Although it would be desirable to have theoretical guarantees of this,
      we argue that such guarantees would not be sufficient to justify the use of these
      models in practice. Instead, we emphasize the importance of taking the variance
      of parameter estimates into account rather than blindly trusting point estimates 
      this is standardly done by using the models to construct statistical hypothesis
      tests, which are then validated empirically via simulation studies. 

PMID- 24722427
TI  - Coulomb interaction effects on the Majorana states in quantum wires.
AB  - The stability of the Majorana modes in the presence of a repulsive interaction is
      studied in the standard semiconductor wire-metallic superconductor configuration.
      The effects of short-range Coulomb interaction, which is incorporated using a
      purely repulsive delta-function to model the strong screening effect due to the
      presence of the superconductor, are determined within a Hartree-Fock
      approximation of the effective Bogoliubov-De Gennes Hamiltonian that describes
      the low-energy physics of the wire. Through a numerical diagonalization procedure
      we obtain interaction corrections to the single particle eigenstates and
      calculate the extended topological phase diagram in terms of the chemical
      potential and the Zeeman energy. We find that, for a fixed Zeeman energy, the
      interaction shifts the phase boundaries to a higher chemical potential, whereas
      for a fixed chemical potential this shift can occur either at lower or higher
      Zeeman energies. These effects can be interpreted as a renormalization of the g
      factor due to the interaction. The minimum Zeeman energy needed to realize
      Majorana fermions decreases with the increasing strength of the Coulomb
      repulsion. Furthermore, we find that in wires with multi-band occupancy this
      effect can be enhanced by increasing the chemical potential, i.e. by occupying
      higher energy bands. 

PMID- 24722426
TI  - MiRNA 17 family regulates cisplatin-resistant and metastasis by targeting
      TGFbetaR2 in NSCLC.
AB  - MicroRNAs (miRNAs) have been proven to play crucial roles in cancer, including
      tumor chemotherapy resistance and metastasis of non-small-cell lung cancer
      (NSCLC). TGFbeta signal pathway abnormality is widely found in cancer and
      correlates with tumor proliferation, apoptosis and metastasis. Here, miR-17, 20a,
      20b were detected down-regulated in A549/DDP cells (cisplatin resistance)
      compared with A549 cells (cisplatin sensitive). Over-expression of miR-17, 20a,
      20b can not only decrease cisplatin-resistant but also reduce migration by
      inhibiting epithelial-to-mesenchymal transition (EMT) in A549/DDP cells. These
      functions of miR-17, 20a, 20b may be caused at least in part via inhibition of
      TGFbeta signal pathway, as miR-17, 20a, 20b are shown to directly target and
      repress TGF-beta receptor 2 (TGFbetaR2) which is an important component of
      TGFbeta signal pathway. Consequently, our study suggests that miRNA 17 family
      (including miR-17, 20a, 20b) can act as TGFbetaR2 suppressor for reversing
      cisplatin-resistant and suppressing metastasis in NSCLC.

PMID- 24722428
TI  - Microenvironment: Endothelial cells create a niche.

PMID- 24722430
TI  - Breast cancer: Hypoxia and XBP1S.

PMID- 24722431
TI  - Kinetochore genes are required to fully activate secretory pathway expansion in
      S. cerevisiae under induced ER stress.
AB  - Basal ER stress occurs when proteins misfold in normal physiological conditions
      and are corrected by the unfolded protein response (UPR). Elevated ER stress
      occurs when misfolding is refractory as found in numerous diseases such as
      atherosclerosis, Type II diabetes and some cancers. In elevated ER stress it is
      unclear whether cells utilise the same or different networks of genes as in basal
      levels of ER stress. To probe this question, we used secretory pathway reporters
      Yip3p-GFP, Erv29p-GFP, Orm2p-GFP and UPREpr-GFP placed on the yeast deletion
      mutant array (DMA) genetic background. The reporter's expression levels, measured
      by automated microscopy, at basal versus elevated ER stress induced by the over
      expression of CPY* were compared. A novel group of kinetochore genes (CTF19
      complex) were found to be uniquely required for full induction of all four ER
      stress reporters in elevated stress. A follow-up reporter screen was developed by
      mating the ctf19Delta kinetochore gene deletion strain into the genome-wide XXXp
      GFP tagged library then testing with over-expressed CPY*. This screen identified
      Bcy1p and Bfr1p as possible signalling points that down-regulate the UPR and
      secretory pathway when kinetochore proteins are absent under elevated stress
      conditions. Bfr1p appears to be a checkpoint that monitors the integrity of
      kinetochores at increased levels of ER stress. This study concludes that
      functional kinetochores are required for full activation of the secretory pathway
      in elevated ER stress and that the responses to basal and elevated levels of ER
      stress require different networks of genes.

PMID- 24722432
TI  - Characterizing and Diminishing Autofluorescence in Formalin-fixed Paraffin
      embedded Human Respiratory Tissue.
AB  - Tissue autofluorescence frequently hampers visualization of immunofluorescent
      markers in formalin-fixed paraffin-embedded respiratory tissues. We assessed nine
      treatments reported to have efficacy in reducing autofluorescence in other tissue
      types. The three most efficacious were Eriochrome black T, Sudan black B and
      sodium borohydride, as measured using white light laser confocal Lambda2 (multi
      lambda) analysis. We also assessed the impact of steam antigen retrieval and
      serum application on human tracheal tissue autofluorescence. Functionally fitting
      this Lambda2 data to 2-dimensional Gaussian surfaces revealed that steam antigen
      retrieval and serum application contribute minimally to autofluorescence and that
      the three treatments are disparately efficacious. Together, these studies provide
      a set of guidelines for diminishing autofluorescence in formalin-fixed paraffin
      embedded human respiratory tissue. Additionally, these characterization
      techniques are transferable to similar questions in other tissue types, as
      demonstrated on frozen human liver tissue and paraffin-embedded mouse lung tissue
      fixed in different fixatives.

PMID- 24722429
TI  - IGF binding proteins in cancer: mechanistic and clinical insights.
AB  - The six members of the family of insulin-like growth factor (IGF) binding
      proteins (IGFBPs) were originally characterized as passive reservoirs of
      circulating IGFs, but they are now understood to have many actions beyond their
      endocrine role in IGF transport. IGFBPs also function in the pericellular and
      intracellular compartments to regulate cell growth and survival - they interact
      with many proteins, in addition to their canonical ligands IGF-I and IGF-II.
      Intranuclear roles of IGFBPs in transcriptional regulation, induction of
      apoptosis and DNA damage repair point to their intimate involvement in tumour
      development, progression and resistance to treatment. Tissue or circulating
      IGFBPs might also be useful as prognostic biomarkers. 

PMID- 24722434
TI  - Prediction of high incidence of dengue in the Philippines.
AB  - BACKGROUND: Accurate prediction of dengue incidence levels weeks in advance of an
      outbreak may reduce the morbidity and mortality associated with this neglected
      disease. Therefore, models were developed to predict high and low dengue
      incidence in order to provide timely forewarnings in the Philippines. METHODS:
      Model inputs were chosen based on studies indicating variables that may impact
      dengue incidence. The method first uses Fuzzy Association Rule Mining techniques
      to extract association rules from these historical epidemiological,
      environmental, and socio-economic data, as well as climate data indicating future
      weather patterns. Selection criteria were used to choose a subset of these rules
      for a classifier, thereby generating a Prediction Model. The models predicted
      high or low incidence of dengue in a Philippines province four weeks in advance.
      The threshold between high and low was determined relative to historical
      incidence data. PRINCIPAL FINDINGS: Model accuracy is described by Positive
      Predictive Value (PPV), Negative Predictive Value (NPV), Sensitivity, and
      Specificity computed on test data not previously used to develop the model.
      Selecting a model using the F0.5 measure, which gives PPV more importance than
      Sensitivity, gave these results: PPV = 0.780, NPV = 0.938, Sensitivity = 0.547,
      Specificity = 0.978. Using the F3 measure, which gives Sensitivity more
      importance than PPV, the selected model had PPV = 0.778, NPV = 0.948, Sensitivity
      = 0.627, Specificity = 0.974. The decision as to which model has greater utility
      depends on how the predictions will be used in a particular situation.
      CONCLUSIONS: This method builds prediction models for future dengue incidence in
      the Philippines and is capable of being modified for use in different situations;
      for diseases other than dengue; and for regions beyond the Philippines. The
      Philippines dengue prediction models predicted high or low incidence of dengue
      four weeks in advance of an outbreak with high accuracy, as measured by PPV, NPV,
      Sensitivity, and Specificity.

PMID- 24722433
TI  - Discovery and validation of an INflammatory PROtein-driven GAstric cancer
      Signature (INPROGAS) using antibody microarray-based oncoproteomics.
AB  - This study aimed to improve gastric cancer (GC) diagnosis by identifying and
      validating an INflammatory PROtein-driven GAstric cancer Signature (hereafter
      INPROGAS) using low-cost affinity proteomics. The detection of 120 cytokines, 43
      angiogenic factors, 41 growth factors, 40 inflammatory factors and 10
      metalloproteinases was performed using commercially available human antibody
      microarray-based arrays. We identified 21 inflammation-related proteins
      (INPROGAS) with significant differences in expression between GC tissues and
      normal gastric mucosa in a discovery cohort of matched pairs (n=10) of
      tumor/normal gastric tissues. Ingenuity pathway analysis confirmed the
      "inflammatory response", "cellular movement" and "immune cell trafficking" as the
      most overrepresented biofunctions within INPROGAS. Using an expanded independent
      validation cohort (n = 22), INPROGAS classified gastric samples as "GC" or "non
      GC" with a sensitivity of 82% (95% CI 59-94) and a specificity of 73% (95% CI 49
      89). The positive predictive value and negative predictive value in this
      validation cohort were 75% (95% CI 53-90) and 80% (95% CI 56-94), respectively.
      The positive predictive value and negative predictive value in this validation
      cohort were 75% (95% CI 53-90) and 80% (95% CI 56-94), respectively. Antibody
      microarray analyses of the GC-associated inflammatory proteome identified a 21
      protein INPROGAS that accurately discriminated GC from noncancerous gastric
      mucosa. 

PMID- 24722435
TI  - An inadvertent but explicable error in calculating number needed to treat for
      reporting survival data.

PMID- 24722436
TI  - A copeptin-based classification of the osmoregulatory defects in the syndrome of
      inappropriate antidiuresis.
AB  - Hyponatremia, the most frequent electrolyte disorder, is caused predominantly by
      the syndrome of inappropriate antidiuresis (SIAD). A comprehensive
      characterization of SIAD subtypes, defined by type of osmotic dysregulation, is
      lacking, but may aid in predicting therapeutic success. Here, we analyzed serial
      measurements of serum osmolality and serum sodium, plasma arginine vasopressin
      (AVP), and plasma copeptin concentrations from 50 patients with hyponatremia who
      underwent hypertonic saline infusion. A close correlation between copeptin
      concentrations and serum osmolality existed in 68 healthy controls, with a mean
      osmotic threshold+/-SD of 282+/-4 mOsM/kg H2O. Furthermore, saline-induced
      changes in copeptin concentrations correlated with changes in AVP concentrations
      in controls and patients. With use of copeptin concentration as a surrogate
      measure of AVP concentration, patients with SIAD could be grouped according to
      osmoregulatory defect: Ten percent of patients had grossly elevated copeptin
      concentrations independent of serum osmolality (type A); 14% had copeptin
      concentrations that increased linearly with rising serum osmolality but had
      abnormally low osmotic thresholds (type B); 44% had normal copeptin
      concentrations independent of osmolality (type C), and 12% had suppressed
      copeptin concentrations independent of osmolality (type D). A novel SIAD subtype
      discovered in 20% of patients was characterized by a linear decrease in copeptin
      concentrations with increasing serum osmolality (type E or "barostat reset"). In
      conclusion, a partial or complete loss of AVP osmoregulation occurs in patients
      with SIAD. Although the mechanisms underlying osmoregulatory defects in
      individual patients are presumably diverse, we hypothesize that treatment
      responses and patient outcomes will vary according to SIAD subtype. 

PMID- 24722438
TI  - Overexpression of Mafb in podocytes protects against diabetic nephropathy.
AB  - We previously showed that the transcription factor Mafb is essential for podocyte
      differentiation and foot process formation. Podocytes are susceptible to injury
      in diabetes, and this injury leads to progression of diabetic nephropathy. In
      this study, we generated transgenic mice that overexpress Mafb in podocytes using
      the nephrin promoter/enhancer. To examine a potential pathogenetic role for Mafb
      in diabetic nephropathy, Mafb transgenic mice were treated with either
      streptozotocin or saline solution. Diabetic nephropathy was assessed by renal
      histology and biochemical analyses of urine and serum. Podocyte-specific
      overexpression of Mafb had no effect on body weight or blood glucose levels in
      either diabetic or control mice. Notably, albuminuria and changes in BUN levels
      and renal histology observed in diabetic wild-type animals were ameliorated in
      diabetic Mafb transgenic mice. Moreover, hyperglycemia-induced downregulation of
      Nephrin was mitigated in diabetic Mafb transgenic mice, and reporter assay
      results suggested that Mafb regulates Nephrin directly. Mafb transgenic glomeruli
      also overexpressed glutathione peroxidase, an antioxidative stress enzyme, and
      levels of the oxidative stress marker 8-hydroxydeoxyguanosine decreased in the
      urine of diabetic Mafb transgenic mice. Finally, Notch2 expression increased in
      diabetic glomeruli, and this effect was enhanced in diabetic Mafb transgenic
      glomeruli. These data indicate Mafb has a protective role in diabetic nephropathy
      through regulation of slit diaphragm proteins, antioxidative enzymes, and Notch
      pathways in podocytes and suggest that Mafb could be a therapeutic target. 

PMID- 24722437
TI  - Direct action of endothelin-1 on podocytes promotes diabetic glomerulosclerosis.
AB  - The endothelin system has emerged as a novel target for the treatment of diabetic
      nephropathy. Endothelin-1 promotes mesangial cell proliferation and sclerosis.
      However, no direct pathogenic effect of endothelin-1 on podocytes has been shown
      in vivo and endothelin-1 signaling in podocytes has not been investigated. This
      study investigated endothelin effects in podocytes during experimental diabetic
      nephropathy. Stimulation of primary mouse podocytes with endothelin-1 elicited
      rapid calcium transients mediated by endothelin type A receptors (ETARs) and
      endothelin type B receptors (ETBRs). We then generated mice with a podocyte
      specific double deletion of ETAR and ETBR (NPHS2
      Cre*Ednra(lox/lox)*Ednrb(lox/lox) [Pod-ETRKO]). In vitro, treatment with
      endothelin-1 increased total beta-catenin and phospho-NF-kappaB expression in
      wild-type glomeruli, but this effect was attenuated in Pod-ETRKO glomeruli. After
      streptozotocin injection to induce diabetes, wild-type mice developed mild
      diabetic nephropathy with microalbuminuria, mesangial matrix expansion,
      glomerular basement membrane thickening, and podocyte loss, whereas Pod-ETRKO
      mice presented less albuminuria and were completely protected from
      glomerulosclerosis and podocyte loss, even when uninephrectomized. Moreover,
      glomeruli from normal and diabetic Pod-ETRKO mice expressed substantially less
      total beta-catenin and phospho-NF-kappaB compared with glomeruli from counterpart
      wild-type mice. This evidence suggests that endothelin-1 drives development of
      glomerulosclerosis and podocyte loss through direct activation of endothelin
      receptors and NF-kappaB and beta-catenin pathways in podocytes. Notably, both the
      expression and function of the ETBR subtype were found to be important.
      Furthermore, these results indicate that activation of the endothelin-1 pathways
      selectively in podocytes mediates pathophysiologic crosstalk that influences
      mesangial architecture and sclerosis.

PMID- 24722439
TI  - Renal-retinal ciliopathy gene Sdccag8 regulates DNA damage response signaling.
AB  - Nephronophthisis-related ciliopathies (NPHP-RCs) are developmental and
      degenerative kidney diseases that are frequently associated with extrarenal
      pathologies such as retinal degeneration, obesity, and intellectual disability.
      We recently identified mutations in a gene encoding the centrosomal protein
      SDCCAG8 as causing NPHP type 10 in humans. To study the role of Sdccag8 in
      disease pathogenesis, we generated a Sdccag8 gene-trap mouse line. Homozygous
      Sdccag8(gt/gt) mice lacked the wild-type Sdccag8 transcript and protein, and
      recapitulated the human phenotypes of NPHP and retinal degeneration. These mice
      exhibited early onset retinal degeneration that was associated with rhodopsin
      mislocalization in the photoreceptors and reduced cone cell numbers, and led to
      progressive loss of vision. By contrast, renal histologic changes occurred later,
      and no global ciliary defects were observed in the kidneys. Instead, renal
      pathology was associated with elevated levels of DNA damage response signaling
      activity. Cell culture studies confirmed the aberrant activation of DNA damage
      response in Sdccag8(gt/gt)-derived cells, characterized by elevated levels of
      gammaH2AX and phosphorylated ATM and cell cycle profile abnormalities. Our
      analysis of Sdccag8(gt/gt) mice indicates that the pleiotropic phenotypes in
      these mice may arise through multiple tissue-specific disease mechanisms. 

PMID- 24722440
TI  - osr1 is required for podocyte development downstream of wt1a.
AB  - Odd-skipped related 1 (Osr1) encodes a zinc finger transcription factor required
      for kidney development. Osr1 deficiency in mice results in metanephric kidney
      agenesis, whereas knockdown or mutation studies in zebrafish revealed that
      pronephric nephrons require osr1 for proximal tubule and podocyte development.
      osr1-deficient pronephric podocyte progenitors express the Wilms' tumor
      suppressor wt1a but do not undergo glomerular morphogenesis or express the foot
      process junctional markers nephrin and podocin. The function of osr1 in podocyte
      differentiation remains unclear, however. Here, we found by double fluorescence
      in situ hybridization that podocyte progenitors coexpress osr1 and wt1a.
      Knockdown of wt1a disrupted podocyte differentiation and prevented expression of
      osr1. Blocking retinoic acid signaling, which regulates wt1a, also prevented osr1
      expression in podocyte progenitors. Furthermore, unlike the osr1-deficient
      proximal tubule phenotype, which can be rescued by manipulation of endoderm
      development, podocyte differentiation was not affected by altered endoderm
      development, as assessed by nephrin and podocin expression in double osr1/sox32
      deficient embryos. These results suggest a different, possibly cell- autonomous
      requirement for osr1 in podocyte differentiation downstream of wt1a. Indeed, osr1
      deficient embryos did not exhibit podocyte progenitor expression of the
      transcription factor lhx1a, and forced expression of activated forms of the lhx1a
      gene product rescued nephrin expression in osr1-deficient podocytes. Our results
      place osr1 in a framework of transcriptional regulators that control the
      expression of podocin and nephrin and thereby mediate podocyte differentiation. 

PMID- 24722441
TI  - Race, class, and AKI.

PMID- 24722442
TI  - Explaining the racial difference in AKI incidence.
AB  - African Americans face higher risk of AKI than Caucasians. The extent to which
      this increased risk is because of differences in clinical, socioeconomic, or
      genetic risk factors is unknown. We evaluated 10,588 African-American and
      Caucasian participants in the Atherosclerosis Risk in Communities study, a
      community-based prospective cohort of middle-aged individuals. Participants were
      followed from baseline study visit (1996-1999) to first hospitalization for AKI
      (defined by billing code), ESRD, death, or December 31, 2010. African-American
      participants were slightly younger (61.7 versus 63.1 years, P<0.001), were more
      often women (64.5% versus 53.2%, P<0.001), and had higher baseline eGFR compared
      with Caucasians. Annual family income, education level, and prevalence of health
      insurance were lower among African Americans than Caucasians. The unadjusted
      incidence of hospitalized AKI was 7.4 cases per 1000 person-years among African
      Americans and 5.8 cases per 1000 person-years among Caucasians (P=0.002). The
      elevated risk of AKI among African Americans persisted after adjustment for
      demographics, cardiovascular risk factors, kidney markers, and time-varying
      number of hospitalizations (adjusted hazard ratio, 1.20; 95% confidence interval
      [95% CI], 1.01 to 1.43; P=0.04); however, accounting for differences in income
      and/or insurance by race attenuated the association (P>0.05). High-risk APOL1
      variants did not associate with AKI among African Americans (demographic-adjusted
      hazard ratio, 1.07; 95% CI, 0.69 to 1.65; P=0.77). In summary, the higher risk of
      AKI among African Americans may be related to disparities in socioeconomic
      status. 

PMID- 24722443
TI  - Endothelin antagonists in diabetic nephropathy: back to basics.

PMID- 24722444
TI  - Characterization of a factor H mutation that perturbs the alternative pathway of
      complement in a family with membranoproliferative GN.
AB  - Complement C3 activation is a characteristic finding in membranoproliferative GN
      (MPGN). This activation can be caused by immune complex deposition or an acquired
      or inherited defect in complement regulation. Deficiency of complement factor H
      has long been associated with MPGN. More recently, heterozygous genetic variants
      have been reported in sporadic cases of MPGN, although their functional
      significance has not been assessed. We describe a family with MPGN and acquired
      partial lipodystrophy. Although C3 nephritic factor was shown in family members
      with acquired partial lipodystrophy, it did not segregate with the renal
      phenotype. Genetic analysis revealed a novel heterozygous mutation in complement
      factor H (R83S) in addition to known risk polymorphisms carried by individuals
      with MPGN. Patients with MPGN had normal levels of factor H, and structural
      analysis of the mutant revealed only subtle alterations. However, functional
      analysis revealed profoundly reduced C3b binding, cofactor activity, and decay
      accelerating activity leading to loss of regulation of the alternative pathway.
      In summary, this family showed a confluence of common and rare functionally
      significant genetic risk factors causing disease. Data from our analysis of these
      factors highlight the role of the alternative pathway of complement in MPGN. 

PMID- 24722445
TI  - The endothelin antagonist atrasentan lowers residual albuminuria in patients with
      type 2 diabetic nephropathy.
AB  - Despite optimal treatment, including renin-angiotensin system (RAS) inhibitors,
      patients with type 2 diabetic nephropathy have high cardiorenal morbidity and
      mortality related to residual albuminuria. We evaluated whether or not
      atrasentan, a selective endothelin A receptor antagonist, further reduces
      albuminuria when administered concomitantly with maximum tolerated labeled doses
      of RAS inhibitors. We enrolled 211 patients with type 2 diabetes, urine
      albumin/creatinine ratios of 300-3500 mg/g, and eGFRs of 30-75 ml/min per 1.73
      m(2) in two identically designed, parallel, multinational, double-blind studies.
      Participants were randomized to placebo (n=50) or to 0.75 mg/d (n=78) or 1.25
      mg/d (n=83) atrasentan for 12 weeks. Compared with placebo, 0.75 mg and 1.25 mg
      atrasentan reduced urine albumin/creatinine ratios by an average of 35% and 38%
      (95% confidence intervals of 24 to 45 and 28 to 47, respectively) and reduced
      albuminuria>=30% in 51% and 55% of participants, respectively. eGFR and office BP
      measurements did not change, whereas 24-hour systolic and diastolic BP, LDL
      cholesterol, and triglyceride levels decreased significantly in both treatment
      groups. Use of atrasentan was associated with a significant increase in weight
      and a reduction in hemoglobin, but rates of peripheral edema, heart failure, or
      other side effects did not differ between groups. However, more patients treated
      with 1.25 mg/d atrasentan discontinued due to adverse events. After stopping
      atrasentan for 30 days, measured parameters returned to pretreatment levels. In
      conclusion, atrasentan reduced albuminuria and improved BP and lipid spectrum
      with manageable fluid overload-related adverse events in patients with type 2
      diabetic nephropathy receiving RAS inhibitors.

PMID- 24722446
TI  - Alterations in the ubiquitin proteasome system in persistent but not reversible
      proteinuric diseases.
AB  - Podocytes are the key cells affected in nephrotic glomerular kidney diseases, and
      they respond uniformly to injury with cytoskeletal rearrangement. In nephrotic
      diseases, such as membranous nephropathy and FSGS, persistent injury often leads
      to irreversible structural damage, whereas in minimal change disease, structural
      alterations are mostly transient. The factors leading to persistent podocyte
      injury are currently unknown. Proteolysis is an irreversible process and could
      trigger persistent podocyte injury through degradation of podocyte-specific
      proteins. We, therefore, analyzed the expression and functional consequence of
      the two most prominent proteolytic systems, the ubiquitin proteasome system (UPS)
      and the autophagosomal/lysosomal system, in persistent and transient podocyte
      injuries. We show that differential upregulation of both proteolytic systems
      occurs in persistent human and rodent podocyte injury. The expression of specific
      UPS proteins in podocytes differentiated children with minimal change disease
      from children with FSGS and correlated with poor clinical outcome. Degradation of
      the podocyte-specific protein alpha-actinin-4 by the UPS depended on oxidative
      modification in membranous nephropathy. Notably, the UPS was overwhelmed in
      podocytes during experimental glomerular disease, resulting in abnormal protein
      accumulation and compensatory upregulation of the autophagosomal/lysosomal
      system. Accordingly, inhibition of both proteolytic systems enhanced proteinuria
      in persistent nephrotic disease. This study identifies altered proteolysis as a
      feature of persistent podocyte injury. In the future, specific UPS proteins may
      serve as new biomarkers or therapeutic targets in persistent nephrotic syndrome. 

PMID- 24722447
TI  - Genetic susceptibility and loss of Nr4a1 enhances macrophage-mediated renal
      injury in CKD.
AB  - Nuclear hormone receptors of the NR4A subgroup have been implicated in cancer,
      atherosclerosis, and metabolic disease. However, little is known about the role
      of these receptors in kidney health or disease. Nr4a1-deficient rats (Nr4a1(-/-))
      developed on a genetic background susceptible to kidney injury (fawn-hooded
      hypertensive rat [FHH]) were evaluated for BP, proteinuria, renal function, and
      metabolic parameters from 4 to 24 weeks-of-age. By week 24, Nr4a1(-/-) rats
      exhibited significantly higher proteinuria (approximately 4-fold) and decreased
      GFR compared with FHH controls. The severity of tubular atrophy, tubular casts,
      and interstitial fibrosis increased significantly in Nr4a1(-/-) rats and was
      accompanied by a large increase in immune cell infiltration, predominantly
      macrophages and to a lesser extent T cells and B cells. Global transcriptome and
      network analyses at weeks 8, 16, and 24 identified several proinflammatory genes
      and pathways differentially regulated between strains. Bone marrow
      crosstransplantation studies demonstrated that kidney injury in Nr4a1(-/-) rats
      was almost completely rescued by bone marrow transplanted from FHH controls. In
      vitro, macrophages isolated from Nr4a1(-/-) rats demonstrated increased immune
      activation compared with FHH-derived macrophages. In summary, the loss of Nr4a1
      in immune cells appears to cause the increased kidney injury and reduced renal
      function observed in the Nr4a1(-/-) model. 

PMID- 24722448
TI  - Iron sucrose accelerates early atherogenesis by increasing superoxide production
      and upregulating adhesion molecules in CKD.
AB  - High-dose intravenous iron supplementation is associated with adverse
      cardiovascular outcomes in patients with CKD, but the underlying mechanism is
      unknown. Our study investigated the causative role of iron sucrose in leukocyte
      endothelium interactions, an index of early atherogenesis, and subsequent
      atherosclerosis in the mouse remnant kidney model. We found that expression
      levels of intracellular cell adhesion molecule-1 (ICAM-1) and vascular cell
      adhesion molecule-1 (VCAM-1) and adhesion of U937 cells increased in iron-treated
      human aortic endothelial cells through upregulated NADPH oxidase (NOx) and NF
      kappaB signaling. We then measured mononuclear-endothelial adhesion and
      atherosclerotic lesions of the proximal aorta in male C57BL/6 mice with subtotal
      nephrectomy, male apolipoprotein E-deficient (ApoE(-/-)) mice with
      uninephrectomy, and sham-operated mice subjected to saline or parenteral iron
      loading. Iron sucrose significantly increased tissue superoxide production,
      expression of tissue cell adhesion molecules, and endothelial adhesiveness in
      mice with subtotal nephrectomy. Moreover, iron sucrose exacerbated
      atherosclerosis in the aorta of ApoE(-/-) mice with uninephrectomy. In patients
      with CKD, intravenous iron sucrose increased circulating mononuclear superoxide
      production, expression of soluble adhesion molecules, and mononuclear-endothelial
      adhesion compared with healthy subjects or untreated patients. In summary, iron
      sucrose aggravated endothelial dysfunction through NOx/NF-kappaB/CAM signaling,
      increased mononuclear-endothelial adhesion, and exacerbated atherosclerosis in
      mice with remnant kidneys. These results suggest a novel causative role for
      therapeutic iron in cardiovascular complications in patients with CKD. 

PMID- 24722449
TI  - Cytomegalovirus and anemia: not just for transplant anymore.

PMID- 24722451
TI  - diRNA-Ago2-RAD51 complexes at double-strand break sites.
AB  - The way in which the DNA damage response signals the presence of DNA lesions and
      mediates DNA repair has not been fully elucidated. Now, Gao et al. reveal that
      diRNA-Ago2 complexes recruit RAD51 to the break sites. 

PMID- 24722450
TI  - Human cytomegalovirus inhibits erythropoietin production.
AB  - Anemia is a feature of CKD and a complication of renal transplantation, often
      caused by impaired production of erythropoietin. The kidney is a target organ for
      human cytomegalovirus (hCMV) in such patients, but it is not known whether hCMV
      effects erythropoietin production. We found that kidneys from patients with CKD
      were positive for hCMV protein and that blood levels of hCMV IgG inversely
      correlated with red blood cell count. In mice, systemic murine cytomegalovirus
      infection decreased serum erythropoietin levels. In human erythropoietin
      producing cells, hCMV inhibited hypoxia-induced expression of erythropoietin mRNA
      and protein. hCMV early gene expression was responsible, as ultraviolet
      inactivated virus had no effect and valganciclovir treatment showed that late
      gene expression was nonessential. Hypoxia-induced gene transcription is
      controlled by the transcription factors hypoxia-inducible transcription factor
      (HIF)-1alpha and HIF2alpha, which are constitutively produced but stable only
      under low oxygen conditions. We found that hCMV inhibited constitutive production
      of HIF2alpha mRNA. HIF2alpha is thought to be the master regulator of
      erythropoietin transcription. Single-cell analysis revealed that nuclear
      accumulation of HIF2alpha was inhibited in hCMV-infected cells, and the extent of
      inhibition correlated with hCMV protein expression. Our findings suggest that
      renal hCMV infection could induce or exacerbate anemia in patients. 

PMID- 24722452
TI  - Structural insights into the TRIM family of ubiquitin E3 ligases.

PMID- 24722453
TI  - The Multifaceted Roles of STAT3 Signaling in the Progression of Prostate Cancer.
AB  - The signal transducer and activator of transcription (STAT)3 governs essential
      functions of epithelial and hematopoietic cells that are often dysregulated in
      cancer. While the role for STAT3 in promoting the progression of many solid and
      hematopoietic malignancies is well established, this review will focus on the
      importance of STAT3 in prostate cancer progression to the incurable metastatic
      castration-resistant prostate cancer (mCRPC). Indeed, STAT3 integrates different
      signaling pathways involved in the reactivation of androgen receptor pathway,
      stem like cells and the epithelial to mesenchymal transition that drive
      progression to mCRPC. As equally important, STAT3 regulates interactions between
      tumor cells and the microenvironment as well as immune cell activation. This
      makes it a major factor in facilitating prostate cancer escape from detection of
      the immune response, promoting an immunosuppressive environment that allows
      growth and metastasis. Based on the multifaceted nature of STAT3 signaling in the
      progression to mCRPC, the promise of STAT3 as a therapeutic target to prevent
      prostate cancer progression and the variety of STAT3 inhibitors used in cancer
      therapies is discussed. 

PMID- 24722454
TI  - Histone deacetylase inhibitor romidepsin induces HIV expression in CD4 T cells
      from patients on suppressive antiretroviral therapy at concentrations achieved by
      clinical dosing.
AB  - Persistent latent reservoir of replication-competent proviruses in memory CD4 T
      cells is a major obstacle to curing HIV infection. Pharmacological activation of
      HIV expression in latently infected cells is being explored as one of the
      strategies to deplete the latent HIV reservoir. In this study, we characterized
      the ability of romidepsin (RMD), a histone deacetylase inhibitor approved for the
      treatment of T-cell lymphomas, to activate the expression of latent HIV. In an in
      vitro T-cell model of HIV latency, RMD was the most potent inducer of HIV (EC50 =
      4.5 nM) compared with vorinostat (VOR; EC50 = 3,950 nM) and other histone
      deacetylase (HDAC) inhibitors in clinical development including panobinostat
      (PNB; EC50 = 10 nM). The HIV induction potencies of RMD, VOR, and PNB paralleled
      their inhibitory activities against multiple human HDAC isoenzymes. In both
      resting and memory CD4 T cells isolated from HIV-infected patients on suppressive
      combination antiretroviral therapy (cART), a 4-hour exposure to 40 nM RMD induced
      a mean 6-fold increase in intracellular HIV RNA levels, whereas a 24-hour
      treatment with 1 uM VOR resulted in 2- to 3-fold increases. RMD-induced
      intracellular HIV RNA expression persisted for 48 hours and correlated with
      sustained inhibition of cell-associated HDAC activity. By comparison, the
      induction of HIV RNA by VOR and PNB was transient and diminished after 24 hours.
      RMD also increased levels of extracellular HIV RNA and virions from both memory
      and resting CD4 T-cell cultures. The activation of HIV expression was observed at
      RMD concentrations below the drug plasma levels achieved by doses used in
      patients treated for T-cell lymphomas. In conclusion, RMD induces HIV expression
      ex vivo at concentrations that can be achieved clinically, indicating that the
      drug may reactivate latent HIV in patients on suppressive cART. 

PMID- 24722455
TI  - Incidence and geographical variation of amyotrophic lateral sclerosis (ALS) in
      Southern Germany--completeness of the ALS registry Swabia.
AB  - Objective of this paper was to investigate the incidence, potential geographical
      clusters and the completeness of the amyotrophic lateral sclerosis (ALS) registry
      in Southern Germany (Swabia). Age-standardized incidence rates (ASR) and ratios
      (SIR) as well as 95% confidence intervals (CI) were estimated at county level.
      Capture-recapture (CARE) procedures were applied taking data source dependency
      into account to estimate the quality of case ascertainment in the ALS registry
      Swabia. We identified 438 ALS cases (53% men, 47% women) in the target population
      of about 8.4 Mio inhabitants. The gender ratio (men?women) was 1.1?1. The mean
      age at onset of ALS was 63.8 (SD = 11.9) years for men and 66.0 (12.2) for women.
      The age distribution peaked in the age group 70-74 years. The ASR of ALS was 2.5
      per 100,000 person years (PY; 95% CI: 2.3-2.7). The mean SIR was 1.1 per 100,000
      PY (95% CI: 1.0-1.2). High SIR suggesting geographical clusters were observed in
      two counties (Goppingen and Bodenseekreis), but the variation was not
      statistically significant (p-values = 0.2 and 0.5). The percentage of CARE
      estimated missing cases was 18.9% in the registry yielding an ASR of 3.1 per
      100,000 PY. The high coverage of the CARE estimated completeness of the ALS
      registry Swabia indicates excellent quality for future projects. Regional
      variations have to be investigated further. 

PMID- 24722457
TI  - Child and adolescent immunizations: selected review of recent US recommendations
      and literature.
AB  - PURPOSE OF REVIEW: To provide a clinically relevant summary of the latest
      research and recommendations regarding childhood and adolescent immunizations.
      RECENT FINDINGS: Childhood vaccination has dramatically reduced pediatric
      morbidity and mortality in the United States. Recent research on childhood and
      adolescent immunizations has focused on expanding the use of current vaccines for
      additional subpopulations as well as the development of new vaccines. In
      particular, data confirming the safety and immunogenicity of vaccines in various
      groups of children have shaped national guidelines. Furthermore, studies on
      vaccine uptake, cost-effectiveness, and impact of vaccination have reinforced the
      importance of adhering to these guidelines. More work needs to be done by
      providers and parents to increase vaccination coverage rates to better protect
      children and adolescents from these serious diseases. In this article, selected
      recent publications and recommendations on the following vaccines are reviewed:
      influenza, meningococcal conjugate, childhood and adolescent/adult formulations
      of diphtheria and tetanus toxoids and acellular pertussis, pneumococcal
      conjugate, and human papillomavirus. SUMMARY: Research on childhood and
      adolescent vaccinations continues to shape future guidelines. Through this work,
      we can learn how to optimize the protection of all children and adolescents
      against vaccine-preventable diseases.

PMID- 24722456
TI  - Antiplatelet activity, P2Y1 and P2Y12 inhibition, and metabolism in plasma of
      stereoisomers of diadenosine 5',5'"-P1 ,P4-dithio-P2,P3
      chloromethylenetetraphosphate.
AB  - BACKGROUND: Diadenosine tetraphosphate (Ap4A), a constituent of platelet dense
      granules, and its P1,P4-dithio and/or P2,P3-chloromethylene analogs, inhibit
      adenosine diphosphate (ADP)-induced platelet aggregation. We recently reported
      that these compounds antagonize both platelet ADP receptors, P2Y1 and P2Y12. The
      most active of those analogs, diadenosine 5',5""-P1,P4-dithio-P2,P3
      chloromethylenetetraphosphate, (compound 1), exists as a mixture of 4
      stereoisomers. OBJECTIVE: To separate the stereoisomers of compound 1 and
      determine their effects on platelet aggregation, platelet P2Y1 and P2Y12 receptor
      antagonism, and their metabolism in human plasma. METHODS: We separated the 4
      diastereomers of compound 1 by preparative reversed-phase chromatography, and
      studied their effect on ADP-induced platelet aggregation, P2Y1-mediated changes
      in cytosolic Ca2+, P2Y12-mediated changes in VASP phosphorylation, and metabolism
      in human plasma. RESULTS: The inhibition of ADP-induced human platelet
      aggregation and human platelet P2Y12 receptor, and stability in human plasma
      strongly depended on the stereo-configuration of the chiral P1- and P4
      phosphorothioate groups, the SPSP diastereomer being the most potent inhibitor
      and completely resistant to degradation in plasma, and the RPRP diastereomer
      being the least potent inhibitor and with the lowest plasma stability. The
      inhibitory activity of SPRP diastereomers depended on the configuration of the
      pseudo-asymmetric carbon of the P2,P3-chloromethylene group, one of the
      configurations being significantly more active than the other. Their plasma
      stability did not differ significantly, being intermediate to that of the SPSP
      and the RPRP diastereomers. CONCLUSIONS: The presently-described stereoisomers
      have utility for structural, mechanistic, and drug development studies of dual
      antagonists of platelet P2Y1 and P2Y12 receptors.

PMID- 24722458
TI  - Atomistic picture for the folding pathway of a hybrid-1 type human telomeric DNA
      G-quadruplex.
AB  - In this work we studied the folding process of the hybrid-1 type human telomeric
      DNA G-quadruplex with solvent and K(+) ions explicitly modeled. Enabled by the
      powerful bias-exchange metadynamics and large-scale conventional molecular
      dynamic simulations, the free energy landscape of this G-DNA was obtained for the
      first time and four folding intermediates were identified, including a triplex
      and a basically formed quadruplex. The simulations also provided atomistic
      pictures for the structures and cation binding patterns of the intermediates. The
      results showed that the structure formation and cation binding are cooperative
      and mutually supporting each other. The syn/anti reorientation dynamics of the
      intermediates was also investigated. It was found that the nucleotides usually
      take correct syn/anti configurations when they form native and stable hydrogen
      bonds with the others, while fluctuating between two configurations when they do
      not. Misfolded intermediates with wrong syn/anti configurations were observed in
      the early intermediates but not in the later ones. Based on the simulations, we
      also discussed the roles of the non-native interactions. Besides, the formation
      process of the parallel conformation in the first two G-repeats and the
      associated reversal loop were studied. Based on the above results, we proposed a
      folding pathway for the hybrid-1 type G-quadruplex with atomistic details, which
      is new and more complete compared with previous ones. The knowledge gained for
      this type of G-DNA may provide a general insight for the folding of the other G
      quadruplexes.

PMID- 24722459
TI  - Effects of maternal exposure to ultrafine carbon black on brain perivascular
      macrophages and surrounding astrocytes in offspring mice.
AB  - Perivascular macrophages (PVMs) constitute a subpopulation of resident
      macrophages in the central nervous system (CNS). They are located at the blood
      brain barrier and can contribute to maintenance of brain functions in both health
      and disease conditions. PVMs have been shown to respond to particle substances
      administered during the prenatal period, which may alter their phenotype over a
      long period. We aimed to investigate the effects of maternal exposure to
      ultrafine carbon black (UfCB) on PVMs and astrocytes close to the blood vessels
      in offspring mice. Pregnant mice were exposed to UfCB suspension by intranasal
      instillation on gestational days 5 and 9. Brains were collected from their
      offspring at 6 and 12 weeks after birth. PVM and astrocyte phenotypes were
      examined by Periodic Acid Schiff (PAS) staining, transmission electron microscopy
      and PAS-glial fibrillary acidic protein (GFAP) double staining. PVM granules were
      found to be enlarged and the number of PAS-positive PVMs was decreased in UfCB
      exposed offspring. These results suggested that in offspring, "normal" PVMs
      decreased in a wide area of the CNS through maternal UfCB exposure. The increase
      in astrocytic GFAP expression level was closely related to the enlargement of
      granules in the attached PVMs in offspring. Honeycomb-like structures in some PVM
      granules and swelling of astrocytic end-foot were observed under electron
      microscopy in the UfCB group. The phenotypic changes in PVMs and astrocytes
      indicate that maternal UfCB exposure may result in changes to brain blood vessels
      and be associated with increased risk of dysfunction and disorder in the
      offspring brain. 

PMID- 24722460
TI  - Six hydrophobins are involved in hydrophobin rodlet formation in Aspergillus
      nidulans and contribute to hydrophobicity of the spore surface.
AB  - Hydrophobins are amphiphilic proteins able to self-assemble at water-air
      interphases and are only found in filamentous fungi. In Aspergillus nidulans two
      hydrophobins, RodA and DewA, have been characterized, which both localize on the
      conidiospore surface and contribute to its hydrophobicity. RodA is the
      constituent protein of very regularly arranged rodlets, 10 nm in diameter. Here
      we analyzed four more hydrophobins, DewB-E, in A. nidulans and found that all six
      hydrophobins contribute to the hydrophobic surface of the conidiospores but only
      deletion of rodA caused loss of the rodlet structure. Analysis of the rodlets in
      the dewB-E deletion strains with atomic force microscopy revealed that the
      rodlets appeared less robust. Expression of DewA and DewB driven from the rodA
      promoter and secreted with the RodA secretion signal in a strain lacking RodA,
      restored partly the hydrophobicity. DewA and B were able to form rodlets to some
      extent but never reached the rodlet structure of RodA. The rodlet-lacking rodA
      deletion strain opens the possibility to systematically study rodlet formation of
      other natural or synthetic hydrophobins. 

PMID- 24722461
TI  - From the analyst's couch: Next-generation antibodies.

PMID- 24722462
TI  - Anti-inflammatory drugs: 'Fish'ing for regulators of inflammation.

PMID- 24722463
TI  - Antiviral drugs: Spanner in the works of filovirus infection.

PMID- 24722464
TI  - Target identification: Stopping beta-cell death in diabetes.

PMID- 24722465
TI  - Weaker signals induce more precise temporal-integration.
AB  - It is well known that our perceptual system integrates local information to
      generate global percepts. Although events in the real world occur over time, it
      is still unclear how we integrate temporally dispersed information. Here, I
      systematically explore the relation between the intensity of local signals and
      the resultant of temporal-integration. Presented sequentially with two directions
      of variably coherent random dot patterns (40 degrees apart), participants were
      instructed to report a perceived motion direction by using a mouse driven cursor.
      As the strength of the motion signal was varied, the behavioral results and
      qualitative analyses indicate existence of two aspects of temporal-integration,
      subthreshold integration and suprathreshold integration. In subthreshold
      integration (when the local signals are subthreshold), stronger signals enhance
      integration. On the other hand, in suprathreshold integration (when the signals
      are above threshold), stronger signals decrease integration. As a result,
      relatively weaker, subthreshold or near threshold signals produce more precise
      temporal-integration than suprathreshold signals. 

PMID- 24722466
TI  - An integrated metabonomic approach to studying metabolic profiles in rat models
      with insulin resistance induced by high fructose.
AB  - Insulin resistance (IR) is a common risk factor for the development of metabolic
      diseases, and has gradually become a hot issue for research. It was reported that
      excessive feeding with high fructose induced insulin resistance in both humans
      and rats. The aim of this study was to investigate the progression of IR and
      identify potential biomarkers in urine, plasma and fecal extracts of high
      fructose-fed rats using a (1)H NMR-based metabonomics approach. The biochemical
      analysis was also performed. The levels of pyruvate and lactate in the plasma of
      the IR model rats were reduced significantly, and the levels of citrate and alpha
      ketoglutaric acid (alpha-KG) in their urine, and the levels of succinate in their
      feces also decreased, suggesting perturbation of energy metabolism. Decreased
      levels of taurine in urine and fecal extracts during the whole experiment,
      together with increased levels of creatine/creatinine in urine, revealed liver
      and kidney injuries. Decreased levels of choline-containing metabolites in urine
      and increased levels of betaine in urine and plasma demonstrated altered
      transmethylation. Changes in hippurate, acetate, propionate and n-butyrate levels
      suggested disturbance of the intestinal flora in the IR rats. This study
      indicated that (1)H NMR-based metabonomics can provide biochemical information on
      the progression of IR and offers a non-invasive means for the discovery of
      potential biomarkers.

PMID- 24722467
TI  - I am right, you are wrong: how biased assimilation increases the perceived gap
      between believers and skeptics of violent video game effects.
AB  - BACKGROUND: Despite hundreds of studies, there is continuing debate about the
      extent to which violent video games increase aggression. Believers argue that
      playing violent video games increases aggression, but this stance is disputed by
      skeptics. The present study addressed believers' and skeptics' responses to
      summaries of scientific studies that do or do not present evidence for increased
      aggression after violent video game play. METHODS/PRINCIPAL FINDINGS:
      Participants (N = 662) indicated whether they believed that violent video games
      increase aggression. Afterwards, they evaluated two opposing summaries of
      fictitious studies on the effects of violent video play. They also reported
      whether their initial belief had changed after reading the two summaries and
      indicated again whether they believed that violent video games increase
      aggression. Results showed that believers evaluated the study showing an effect
      more favorably than a study showing no effect, whereas the opposite was observed
      for skeptics. Moreover, both believers and skeptics reported to become more
      convinced of their initial view. In contrast, for actual attitude change, a
      depolarization effect was found. CONCLUSIONS/SIGNIFICANCE: These results suggest
      that biased assimilation of new information leads believers and skeptics to
      become more rather than less certain of their views. Hence, even when confronted
      with mixed and inconclusive evidence, the perceived gap between both sides of the
      argument increases.

PMID- 24722468
TI  - P150glued-associated disorders are caused by activation of intrinsic apoptotic
      pathway.
AB  - Mutations in p150glued cause hereditary motor neuropathy with vocal cord
      paralysis (HMN7B) and Perry syndrome (PS). Here we show that both overexpression
      of p150glued mutants and knockdown of endogenous p150glued induce apoptosis.
      Overexpression of a p150glued plasmid containing either a HMN7B or PS mutation
      resulted in cytoplasmic p150glued-positive aggregates and was associated with
      cell death. Cells containing mutant p150glued aggregates underwent apoptosis that
      was characterized by an increase in cleaved caspase-3- or Annexin V-positive
      cells and was attenuated by both zVAD-fmk (a pan-caspase inhibitor) application
      and caspase-3 siRNA knockdown. In addition, overexpression of mutant p150glued
      decreased mitochondrial membrane potentials and increased levels of translocase
      of the mitochondrial outer membrane (Tom20) protein, indicating accumulation of
      damaged mitochondria. Importantly, siRNA knockdown of endogenous p150glued
      independently induced apoptosis via caspase-8 activation and was not associated
      with mitochondrial morphological changes. Simultaneous knockdown of endogenous
      p150glued and overexpression of mutant p150glued had additive apoptosis induction
      effects. These findings suggest that both p150glued gain-of-toxic-function and
      loss-of-physiological-function can cause apoptosis and may underlie the
      pathogenesis of p150glued-associated disorders.

PMID- 24722469
TI  - A new mosaic pattern in glioma vascularization: exogenous endothelial progenitor
      cells integrating into the vessels containing tumor-derived endothelial cells.
AB  - Emerging evidence suggests that glioma stem-like cells (GSCs)
      transdifferentiating into vascular endothelial cells (ECs) possibly contributes
      to tumor resistance to antiangiogenic therapy. Endothelial progenitor cells
      (EPCs), showing active migration and incorporation into neovasculature of glioma,
      may be a good vehicle for delivering genes to target GSCs transdifferentiation.
      Here, we found a new mosaic pattern that exogenous EPCs integrated into the
      vessels containing the tumor-derived ECs in C6 glioma rat model. Further, we
      evaluated the effect of these homing EPCs on C6 glioma cells
      transdifferentiation. The transdifferentiation frequency of C6 glioma cells and
      the expressions of key factors on GSCs transdifferentiation, i.e. HIF-1alpha,
      Notch1, and Flk1 in gliomas with or without EPCs transplantation showed no
      significant difference. Additionally, magnetic resonance imaging could track the
      migration and incorporation of EPCs into glioma in vivo, which was confirmed by
      Prussian blue staining. The number of magnetically labeled EPCs estimated from T2
      maps correlated well with direct measurements of labeled cell counts by flow
      cytometry. Taken together, our findings may provide a rational base for the
      future application of EPCs as a therapeutic and imaging probe to overcome
      antiangiogenic resistance for glioma and monitor the efficacy of this treatment. 

PMID- 24722470
TI  - The role of canonical transient receptor potential channels in seizure and
      excitotoxicity.
AB  - Canonical transient receptor potential (TRPC) channels are a family of polymodal
      cation channels with some degree of Ca2+ permeability. Although initially thought
      to be channels mediating store-operated Ca2+ influx, TRPC channels can be
      activated by stimulation of Gq-coupled G-protein coupled receptors, or by an
      increase in intracellular free Ca2+ concentration. Thus, activation of TRPC
      channels could be a common downstream event of many signaling pathways that
      contribute to seizure and excitotoxicity, such as N-methyl-D-aspartate (NMDA)
      receptor-mediated Ca2+ influx, or metabotropic glutamate receptor activation.
      Recent studies with genetic ablation of various TRPC family members have
      demonstrated that TRPC channels, in particular heteromeric TRPC1/4 channels and
      homomeric TRPC5 channels, play a critical role in both pilocarpine-induced acute
      seizures and neuronal cell death. However, exact underlying mechanisms remain to
      be fully elucidated, and selective TRPC modulators and antibodies with better
      specificity are urgently needed for future research. 

PMID- 24722472
TI  - CKD-EPI and cockcroft-gault equations identify similar candidates for neoadjuvant
      chemotherapy in muscle-invasive bladder cancer.
AB  - Clinical guidelines suggest neoadjuvant cisplatin-based chemotherapy prior to
      cystectomy in the setting of muscle-invasive bladder cancer (MIBC). A creatinine
      clearance (CrCl) >60 mL/min is frequently used to characterize cisplatin-eligible
      patients, and use of the CKD-EPI equation to estimate CrCl has been advocated.
      From a prospectively maintained institutional database, patients with MIBC who
      received cystectomy were identified and clinicopathologic information was
      ascertained. CrCl prior to surgery was computed using three equations: (1)
      Cockcroft-Gault (CG), (2) CKD-EPI, and (3) MDRD. The primary objective was to
      determine if the CG and CKD-EPI equations identified a different proportion of
      patients who were cisplatin-eligible, based on an estimated CrCl of >60 mL/min.
      Cisplatin-eligibility was also assessed in subsets based on age, CCI score and
      race. Actuarial rates of neoadjuvant cisplatin-based chemotherapy use were also
      reported. Of 126 patients, 70% and 71% of patients were found to be cisplatin
      eligible by the CKD-EPI and CG equations, respectively (P = 0.9). The MDRD did
      not result in significantly different characterization of cisplatin-eligibility
      as compared to the CKD-EPI and CG equations. In the subset of patients age >80,
      the CKD-EPI equation identified a much smaller proportion of cisplatin-eligible
      patients (25%) as compared to the CG equation (50%) or the MDRD equation (63%).
      Only 34 patients (27%) received neoadjuvant cisplatin-based chemotherapy. Of the
      92 patients who did not receive neoadjuvant chemotherapy, 64% had a CrCl >60
      mL/min by CG. In contrast to previous reports, the CKD-EPI equation does not
      appear to characterize a broader span of patients as cisplatin-eligible. Older
      patients (age >80) may less frequently be characterized as cisplatin-eligible by
      CKD-EPI. The discordance between actual rates of neoadjuvant chemotherapy use and
      rates of cisplatin eligibility suggest that other factors (e.g., patient and
      physician preference) may guide clinical decision-making. 

PMID- 24722473
TI  - T-cell regulation in lepromatous leprosy.
AB  - Regulatory T (Treg) cells are known for their role in maintaining self-tolerance
      and balancing immune reactions in autoimmune diseases and chronic infections.
      However, regulatory mechanisms can also lead to prolonged survival of pathogens
      in chronic infections like leprosy and tuberculosis (TB). Despite high humoral
      responses against Mycobacterium leprae (M. leprae), lepromatous leprosy (LL)
      patients have the characteristic inability to generate T helper 1 (Th1) responses
      against the bacterium. In this study, we investigated the unresponsiveness to M.
      leprae in peripheral blood mononuclear cells (PBMC) of LL patients by analysis of
      IFN-gamma responses to M. leprae before and after depletion of CD25+ cells, by
      cell subsets analysis of PBMC and by immunohistochemistry of patients' skin
      lesions. Depletion of CD25+ cells from total PBMC identified two groups of LL
      patients: 7/18 (38.8%) gained in vitro responsiveness towards M. leprae after
      depletion of CD25+ cells, which was reversed to M. leprae-specific T-cell
      unresponsiveness by addition of autologous CD25+ cells. In contrast, 11/18
      (61.1%) remained anergic in the absence of CD25+ T-cells. For both groups mitogen
      induced IFN-gamma was, however, not affected by depletion of CD25+ cells. In M.
      leprae responding healthy controls, treated lepromatous leprosy (LL) and
      borderline tuberculoid leprosy (BT) patients, depletion of CD25+ cells only
      slightly increased the IFN-gamma response. Furthermore, cell subset analysis
      showed significantly higher (p = 0.02) numbers of FoxP3+ CD8+CD25+ T-cells in LL
      compared to BT patients, whereas confocal microscopy of skin biopsies revealed
      increased numbers of CD68+CD163+ as well as FoxP3+ cells in lesions of LL
      compared to tuberculoid and borderline tuberculoid leprosy (TT/BT) lesions. Thus,
      these data show that CD25+ Treg cells play a role in M. leprae-Th1
      unresponsiveness in LL. 

PMID- 24722474
TI  - Evaluation of Physicians' Cognitive Styles.
AB  - BACKGROUND: Patient outcomes critically depend on accuracy of physicians'
      judgment, yet little is known about individual differences in cognitive styles
      that underlie physicians' judgments. The objective of this study was to assess
      physicians' individual differences in cognitive styles relative to age,
      experience, and degree and type of training. METHODS: Physicians at different
      levels of training and career completed a web-based survey of 6 scales measuring
      individual differences in cognitive styles (maximizing v. satisficing, analytical
      v. intuitive reasoning, need for cognition, intolerance toward ambiguity,
      objectivism, and cognitive reflection). We measured psychometric properties
      (Cronbach's alpha) of scales; relationship of age, experience, degree, and type
      of training; responses to scales; and accuracy on conditional inference task.
      RESULTS: The study included 165 trainees and 56 attending physicians (median age
      31 years; range 25-69 years). All 6 constructs showed acceptable psychometric
      properties. Surprisingly, we found significant negative correlation between age
      and satisficing (r = -0.239; P = 0.017). Maximizing (willingness to engage in
      alternative search strategy) also decreased with age (r = -0.220; P = 0.047).
      Number of incorrect inferences negatively correlated with satisficing (r = 
      0.246; P = 0.014). Disposition to suppress intuitive responses was associated
      with correct responses on 3 of 4 inferential tasks. Trainees showed a tendency to
      engage in analytical thinking (r = 0.265; P = 0.025), while attendings displayed
      inclination toward intuitive-experiential thinking (r = 0.427; P = 0.046).
      However, trainees performed worse on conditional inference task. CONCLUSION:
      Physicians capable of suppressing an immediate intuitive response to questions
      and those scoring higher on rational thinking made fewer inferential mistakes. We
      found a negative correlation between age and maximizing: Physicians who were more
      advanced in their careers were less willing to spend time and effort in an
      exhaustive search for solutions. However, they appeared to have maintained their
      "mindware" for effective problem solving.

PMID- 24722475
TI  - Cognition and pain.
AB  - PURPOSE OF REVIEW: Pain and cognition share common neural substrates and are
      known to interact reciprocally. This has implications for treatment and
      management of pain conditions; pain can negatively affect cognitive performance,
      whereas cognitively demanding tasks may reduce pain perception. This article will
      review recent research investigating the impact of pain on cognition and the
      cognitive modulation of pain. RECENT FINDINGS: Recent clinical and preclinical
      studies have provided new evidence for impairment of cognition in pain with a
      focus on the type of cognitive construct affected and the influence of factors
      such as age and pain localization. Reduced connectivity between important brain
      structures has emerged as a possible underlying mechanism. Imaging studies have
      continued to identify neuroanatomical structures involved in different types of
      cognitive pain modulation, and attempts have been made to delineate the
      descending pathways by which pain relief is achieved. New and established methods
      to investigate cognitive modulation of pain in animal models have revealed
      insights into the molecular and neurochemical mechanisms involved. SUMMARY:
      Progress has been made in understanding the complex relationship between pain and
      cognitive function. However, both synthesis of current research findings and
      further novel research studies are required to maximize the therapeutic
      potential.

PMID- 24722476
TI  - Pain: nonmalignant disease.

PMID- 24722478
TI  - Innate lymphoid cells: breathing into allergic inflammation.

PMID- 24722477
TI  - Mechanisms regulating skin immunity and inflammation.
AB  - Immune responses in the skin are important for host defence against pathogenic
      microorganisms. However, dysregulated immune reactions can cause chronic
      inflammatory skin diseases. Extensive crosstalk between the different cellular
      and microbial components of the skin regulates local immune responses to ensure
      efficient host defence, to maintain and restore homeostasis, and to prevent
      chronic disease. In this Review, we discuss recent findings that highlight the
      complex regulatory networks that control skin immunity, and we provide new
      paradigms for the mechanisms that regulate skin immune responses in host defence
      and in chronic inflammation. 

PMID- 24722479
TI  - FOXP3 and scurfy: how it all began.
AB  - It has been 65 years since the scurfy mutation arose spontaneously in mice at the
      Oak Ridge National Laboratory in the United States, and it is 13 years since the
      molecular cloning of the forkhead box P3 (FOXP3) gene was reported. In this
      Timeline article, we review the events that have occurred during and since this
      time. This is not meant as an exhaustive review of the biology of FOXP3 or of
      regulatory T cells, rather it is an attempt to highlight the landmark events that
      have demonstrated the importance of FOXP3 in immune function. These events have
      driven, and continue to drive, the extensive research effort to fully understand
      the role of regulatory T cells in the immune system. 

PMID- 24722480
TI  - Inflammasomes: polymeric assembly.

PMID- 24722481
TI  - rDock: a fast, versatile and open source program for docking ligands to proteins
      and nucleic acids.
AB  - Identification of chemical compounds with specific biological activities is an
      important step in both chemical biology and drug discovery. When the structure of
      the intended target is available, one approach is to use molecular docking
      programs to assess the chemical complementarity of small molecules with the
      target; such calculations provide a qualitative measure of affinity that can be
      used in virtual screening (VS) to rank order a list of compounds according to
      their potential to be active. rDock is a molecular docking program developed at
      Vernalis for high-throughput VS (HTVS) applications. Evolved from RiboDock, the
      program can be used against proteins and nucleic acids, is designed to be
      computationally very efficient and allows the user to incorporate additional
      constraints and information as a bias to guide docking. This article provides an
      overview of the program structure and features and compares rDock to two
      reference programs, AutoDock Vina (open source) and Schrodinger's Glide
      (commercial). In terms of computational speed for VS, rDock is faster than Vina
      and comparable to Glide. For binding mode prediction, rDock and Vina are superior
      to Glide. The VS performance of rDock is significantly better than Vina, but
      inferior to Glide for most systems unless pharmacophore constraints are used; in
      that case rDock and Glide are of equal performance. The program is released under
      the Lesser General Public License and is freely available for download, together
      with the manuals, example files and the complete test sets, at
      http://rdock.sourceforge.net/ 

PMID- 24722482
TI  - Syntenin increases the invasiveness of small cell lung cancer cells by activating
      p38, AKT, focal adhesion kinase and SP1.
AB  - Syntenin is a PDZ domain-containing adaptor protein that has been recently shown
      to regulate migration and invasion in several tumors. Small cell lung cancer
      (SCLC) is notorious for its invasiveness and strong potential for metastasis. We
      therefore studied the influence of syntenin on the invasiveness of SCLC.
      Immunohistochemistry in tumor tissues showed that syntenin was more frequently
      expressed in small cell carcinomas than other neuroendocrine tumors, such as
      carcinoids and neuroblastomas, suggesting that syntenin expression may be related
      to more aggressive forms of neuroendocrine tumors. In SCLC patients, syntenin
      overexpression in tumor cells was significantly associated with more extensive
      and advanced disease at the time of diagnosis (P=0.029). Overexpression of
      syntenin in SCLC cells that were intrinsically syntenin-low increased the
      invasiveness of cells and led to the induction of extracellular matrix (ECM)
      degrading membrane type 1-matrix metalloproteinase (MT1-MMP) and matrix
      metalloproteinase 2 (MMP2). In contrast, suppression of syntenin in syntenin-high
      cells was associated with the downregulation of MT1-MMP. Contrary to the results
      of previous studies using malignant melanomas and breast carcinomas, signaling
      cascades were shown to be further transduced through p38 MAPK and PI3K/AKT, with
      activation of SP1 rather than NF-kappaB, under circumstances not involving ECM
      interaction. In addition, the upstream molecule focal adhesion kinase was induced
      by syntenin activation, in spite of the absence of ECM interaction. These results
      suggest that syntenin might contribute to the invasiveness of SCLC and could be
      utilized as a new therapeutic target for controlling invasion and metastasis in
      SCLC. 

PMID- 24722483
TI  - IgE regulates the expression of smMLCK in human airway smooth muscle cells.
AB  - Previous studies have shown that enhanced accumulation of contractile proteins
      such as smooth muscle myosin light chain kinase (smMLCK) plays a major role in
      human airway smooth muscle cells (HASM) cell hypercontractility and hypertrophy.
      Furthermore, serum IgE levels play an important role in smooth muscle
      hyperreactivity. However, the effect of IgE on smMLCK expression has not been
      investigated. In this study, we demonstrate that IgE increases the expression of
      smMLCK at mRNA and protein levels. This effect was inhibited significantly with
      neutralizing abs directed against FcepsilonRI but not with anti
      FcepsilonRII/CD23. Furthermore, Syk knock down and pharmacological inhibition of
      mitogen activated protein kinases (MAPK) (ERK1/2, p38, and JNK) and
      phosphatidylinositol 3-kinase (PI3K) significantly diminished the IgE-mediated
      upregulation of smMLCK expression in HASM cells. Taken together, our data suggest
      a role of IgE in regulating smMLCK in HASM cells. Therefore, targeting the
      FcepsilonRI activation on HASM cells may offer a novel approach in controlling
      the bronchomotor tone in allergic asthma. 

PMID- 24722485
TI  - Estimation of the relative sensitivity of qPCR analysis using pooled samples.
AB  - The high sensitivity of qPCR makes it a desirable diagnostic method in
      epidemiological surveillance programs. However, due to high costs, the use of
      pooling has been suggested. In this paper, an algorithm based on the Montecarlo
      method has been designed and implemented. The algorithm had been tested in many
      different situations, and finally it was validated with a real dataset. Moreover,
      based on the results obtained and depending on pooling conditions, a drastic
      decrease of sensitivity is observed. 

PMID- 24722484
TI  - Role of capsule and O antigen in the virulence of uropathogenic Escherichia coli.
AB  - Urinary tract infection (UTI) is one of the most common bacterial infections in
      humans, with uropathogenic Escherichia coli (UPEC) the leading causative
      organism. UPEC has a number of virulence factors that enable it to overcome host
      defenses within the urinary tract and establish infection. The O antigen and the
      capsular polysaccharide are two such factors that provide a survival advantage to
      UPEC. Here we describe the application of the rpsL counter selection system to
      construct capsule (kpsD) and O antigen (waaL) mutants and complemented
      derivatives of three reference UPEC strains: CFT073 (O6:K2:H1), RS218 (O18:K1:H7)
      and 1177 (O1:K1:H7). We observed that while the O1, O6 and O18 antigens were
      required for survival in human serum, the role of the capsule was less clear and
      linked to O antigen type. In contrast, both the K1 and K2 capsular antigens
      provided a survival advantage to UPEC in whole blood. In the mouse urinary tract,
      mutation of the O6 antigen significantly attenuated CFT073 bladder colonization.
      Overall, this study contrasts the role of capsule and O antigen in three common
      UPEC serotypes using defined mutant and complemented strains. The combined
      mutagenesis-complementation strategy can be applied to study other virulence
      factors with complex functions both in vitro and in vivo.

PMID- 24722486
TI  - Dynamical screening effects in correlated electron materials-a progress report on
      combined many-body perturbation and dynamical mean field theory: 'GW + DMFT'.
AB  - We give a summary of recent progress in the field of electronic structure
      calculations for materials with strong electronic Coulomb correlations. The
      discussion focuses on developments beyond the by now well established combination
      of density functional and dynamical mean field theory dubbed 'LDA + DMFT'. It is
      organized around the description of dynamical screening effects in the solid.
      Indeed, screening in the solid gives rise to dynamical local Coulomb interactions
      U(omega) (Aryasetiawan et al 2004 Phys. Rev. B 70 195104), and this frequency
      dependence leads to effects that cannot be neglected in a truly first principles
      description. We review the recently introduced extension of LDA + DMFT to
      dynamical local Coulomb interactions 'LDA + U(omega) + DMFT' (Casula et al 2012
      Phys. Rev. B 85 035115, Werner et al 2012 Nature Phys. 1745-2481). A reliable
      description of dynamical screening effects is also a central ingredient of the
      'GW + DMFT' scheme (Biermann et al 2003 Phys. Rev. Lett. 90 086402), a
      combination of many-body perturbation theory in Hedin's GW approximation and
      dynamical mean field theory. Recently, the first GW + DMFT calculations including
      dynamical screening effects for real materials have been achieved, with
      applications to SrV O3 (Tomczak et al 2012 Europhys. Lett. 100 67001, Tomczak et
      al Phys. Rev. B submitted (available electronically as arXiv:1312.7546)) and
      adatom systems on surfaces (Hansmann et al 2013 Phys. Rev. Lett. 110 166401). We
      review these and comment on further perspectives in the field. This review is an
      attempt to put elements of the original works into the broad perspective of the
      development of truly first principles techniques for correlated electron
      materials.

PMID- 24722487
TI  - The immunoregulation effect of alpha 1-antitrypsin prolong beta-cell survival
      after transplantation.
AB  - Islet transplantation has considerable potential as a cure for diabetes. However,
      the difficulties that arise from inflammation and the immunological rejection of
      transplants must be addressed for islet transplantation to be successful. Alpha 1
      antitrypsin (AAT) inhibits the damage on beta cells caused by inflammatory
      reactions and promotes beta-cell survival and proliferation. This protein also
      induces specific immune tolerance to transplanted beta cells. However, whether
      the expression of AAT in beta cells themselves could eliminate or decrease
      immunological rejection of transplants is not clear. Therefore, we established a
      beta cell line (NIT-hAAT) that stably expresses human AAT. Interestingly, in a
      cytotoxic T lymphocyte (CTL)-killing assay, we found that hAAT reduced apoptosis
      and inflammatory cytokine production in NIT-1 cells and regulated the Th1/Th2
      cytokine balance in vitro. In vivo transplantation of NIT-hAAT cells into mice
      with diabetes showed hAAT inhibited immunological rejection for a short period of
      time and increased the survival of transplanted beta cells. This study
      demonstrated that hAAT generated remarkable immunoprotective and immunoregulation
      effects in a model of beta cell islet transplantation for diabetes model. 

PMID- 24722488
TI  - Post-translational decrease in respiratory chain proteins in the Polg mutator
      mouse brain.
AB  - Mitochondrial DNA damage is thought to be a causal contributor to aging as mice
      with inactivating mutations in polymerase gamma (Polg) develop a progeroid
      phenotype. To further understand the molecular mechanisms underlying this
      phenotype, we used iTRAQ and RNA-Seq to determine differences in protein and mRNA
      abundance respectively in the brains of one year old Polg mutator mice compared
      to control animals. We found that mitochondrial respiratory chain proteins are
      specifically decreased in abundance in the brains of the mutator mice, including
      several nuclear encoded mitochondrial components. However, we found no evidence
      that the changes we observed in protein levels were the result of decreases in
      mRNA expression. These results show that there are post-translational effects
      associated with mutations in Polg.

PMID- 24722489
TI  - Cytosolic peroxidases protect the lysosome of bloodstream African trypanosomes
      from iron-mediated membrane damage.
AB  - African trypanosomes express three virtually identical non-selenium glutathione
      peroxidase (Px)-type enzymes which preferably detoxify lipid-derived
      hydroperoxides. As shown previously, bloodstream Trypanosoma brucei lacking the
      mitochondrial Px III display only a weak and transient proliferation defect
      whereas parasites that lack the cytosolic Px I and Px II undergo extremely fast
      lipid peroxidation and cell lysis. The phenotype can completely be rescued by
      supplementing the medium with the alpha-tocopherol derivative Trolox. The
      mechanism underlying the rapid cell death remained however elusive. Here we show
      that the lysosome is the origin of the cellular injury. Feeding the px I-II
      knockout parasites with Alexa Fluor-conjugated dextran or LysoTracker in the
      presence of Trolox yielded a discrete lysosomal staining. Yet upon withdrawal of
      the antioxidant, the signal became progressively spread over the whole cell body
      and was completely lost, respectively. T. brucei acquire iron by endocytosis of
      host transferrin. Supplementing the medium with iron or transferrin induced,
      whereas the iron chelator deferoxamine and apo-transferrin attenuated lysis of
      the px I-II knockout cells. Immunofluorescence microscopy with MitoTracker and
      antibodies against the lysosomal marker protein p67 revealed that disintegration
      of the lysosome precedes mitochondrial damage. In vivo experiments confirmed the
      negligible role of the mitochondrial peroxidase: Mice infected with px III
      knockout cells displayed only a slightly delayed disease development compared to
      wild-type parasites. Our data demonstrate that in bloodstream African
      trypanosomes, the lysosome, not the mitochondrion, is the primary site of
      oxidative damage and cytosolic trypanothione/tryparedoxin-dependent peroxidases
      protect the lysosome from iron-induced membrane peroxidation. This process
      appears to be closely linked to the high endocytic rate and distinct iron
      acquisition mechanisms of the infective stage of T. brucei. The respective
      knockout of the cytosolic px I-II in the procyclic insect form resulted in cells
      that were fully viable in Trolox-free medium. 

PMID- 24722490
TI  - Archaeal amoA and ureC genes and their transcriptional activity in the Arctic
      Ocean.
AB  - Thaumarchaeota and the gene encoding for a subunit of ammonia monooxygenase
      (amoA) are ubiquitous in Polar Seas, and some Thaumarchaeota also have a gene
      coding for ureC, diagnostic for urease. Using quantitative PCR we investigated
      the occurrence of genes and transcripts of ureC and amoA in Arctic samples from
      winter, spring and summer. AmoA genes, ureC genes and amoA transcripts were
      always present, but ureC transcripts were rarely detected. Over a 48 h light
      manipulation experiment amoA transcripts persisted under light and dark
      conditions, but not ureC transcripts. In addition, maxima for amoA transcript
      were nearer the surface compared to amoA genes. Clone libraries using DNA
      template recovered shallow and deep amoA clades but only the shallow clade was
      recovered from cDNA (from RNA). These results imply environmental control of amoA
      expression with direct or indirect light effects, and rare ureC expression
      despite its widespread occurrence in the Arctic Ocean.

PMID- 24722491
TI  - Functional characterization of the type III secretion ATPase SsaN encoded by
      Salmonella pathogenicity island 2.
AB  - A type III secretion system (T3SS) is utilized by a large number of gram-negative
      bacteria to deliver effectors directly into the cytosol of eukaryotic host cells.
      One essential component of a T3SS is an ATPase that catalyzes the unfolding of
      proteins, which is followed by the translocation of effectors through an
      injectisome. Here we demonstrate a functional role of the ATPase SsaN, a
      component of Salmonella pathogenicity island 2 T3SS (T3SS-2) in Salmonella
      enterica serovar Typhimurium. SsaN hydrolyzed ATP in vitro and was essential for
      T3SS function and Salmonella virulence in vivo. Protein-protein interaction
      analyses revealed that SsaN interacted with SsaK and SsaQ to form the C ring
      complex. SsaN and its complex co-localized to the membrane fraction under T3SS-2
      inducing conditions. In addition, SsaN bound to Salmonella pathogenicity island 2
      (SPI-2) specific chaperones, including SsaE, SseA, SscA, and SscB that
      facilitated translocator/effector secretion. Using an in vitro chaperone release
      assay, we demonstrated that SsaN dissociated a chaperone-effector complex, SsaE
      and SseB, in an ATP-dependent manner. Effector release was dependent on a
      conserved arginine residue at position 192 of SsaN, and this was essential for
      its enzymatic activity. These results strongly suggest that the T3SS-2-associated
      ATPase SsaN contributes to T3SS-2 effector translocation efficiency. 

PMID- 24722492
TI  - The plant endomembrane system--a complex network supporting plant development and
      physiology.

PMID- 24722493
TI  - Musculoskeletal complications in type 1 diabetes.
AB  - OBJECTIVE: The development of periarticular thickening of skin on the hands and
      limited joint mobility (cheiroarthropathy) is associated with diabetes and can
      lead to significant disability. The objective of this study was to describe the
      prevalence of cheiroarthropathy in the well-characterized Diabetes Control and
      Complications Trial/Epidemiology of Diabetes Interventions and Complications
      (DCCT/EDIC) cohort and examine associated risk factors, microvascular
      complications, and the effect of former DCCT therapy (intensive [INT] vs.
      conventional [CONV]) on its development. RESEARCH DESIGN AND METHODS: This cross
      sectional analysis was performed in 1,217 participants (95% of the active cohort)
      in EDIC years 18/19 after an average of 24 years of follow-up. Cheiroarthropathy
      defined as the presence of any one of the following: adhesive capsulitis, carpal
      tunnel syndrome, flexor tenosynovitis, Dupuytren's contracture, or a positive
      prayer sign-was assessed using a targeted medical history and standardized
      physical examination. A self-administered questionnaire (Disabilities of the Arm,
      Shoulder and Hand [DASH]) assessed functional disability. RESULTS:
      Cheiroarthropathy was present in 66% of subjects (64% of the INT group and 68% of
      the CONV group; P = 0.1640) and was associated with age, sex, diabetes duration,
      skin intrinsic fluorescence, HbA1c, neuropathy, and retinopathy (P < 0.005 for
      each). DASH functional disability scores were worse among subjects with
      cheiroarthropathy (P < 0.0001). CONCLUSIONS: Cheiroarthropathy is common in
      people with type 1 diabetes of long duration (~30 years) and is related to longer
      duration and higher levels of glycemia. Clinicians should include
      cheiroarthropathy in their routine history and physical examination of patients
      with type 1 diabetes because it causes clinically significant functional
      disability.

PMID- 24722494
TI  - Empagliflozin as add-on to metformin in patients with type 2 diabetes: a 24-week,
      randomized, double-blind, placebo-controlled trial.
AB  - OBJECTIVE: To investigate the efficacy and tolerability of empagliflozin as an
      add-on to metformin therapy in patients with type 2 diabetes. RESEARCH DESIGN AND
      METHODS: Patients with HbA1c levels of >=7% to <= 10% (>=53 to <=86 mmol/mol)
      while receiving metformin (>=1,500 mg/day) were randomized and treated with once
      daily treatment with empagliflozin 10 mg (n = 217), empagliflozin 25 mg (n =
      213), or placebo (n = 207) for 24 weeks. The primary end point was the change in
      HbA1c level from baseline at week 24. Key secondary end points were changes from
      baseline in weight and mean daily glucose (MDG) at week 24. RESULTS: At week 24,
      adjusted mean (SE) changes from baseline in HbA1c were -0.13% (0.05)% (-1.4 [0.5]
      mmol/mol) with placebo, -0.70% (0.05)% (-7.7 [0.5] mmol/mol) with empagliflozin
      10 mg, and -0.77% (0.05)% (-8.4 [0.5] mmol/mol) with empagliflozin 25 mg (both P
      < 0.001). Empagliflozin significantly reduced MDG level and systolic and
      diastolic blood pressure (BP) versus placebo. Adjusted mean (SE) changes from
      baseline in weight were -0.45 kg (0.17 kg) with placebo, -2.08 kg (0.17 kg) with
      empagliflozin 10 mg, and -2.46 kg (0.17 kg) with empagliflozin 25 mg (both P <
      0.001). Adverse events (AEs) were similar across groups (placebo 58.7%;
      empagliflozin 49.5-57.1%). Confirmed hypoglycemic AEs were reported in 0.5%,
      1.8%, and 1.4% of patients receiving placebo, empagliflozin 10 mg, and
      empagliflozin 25 mg, respectively. Events consistent with urinary tract
      infections were reported in 4.9%, 5.1%, and 5.6% of patients, and events
      consistent with genital infections were reported in 0%, 3.7%, and 4.7% of
      patients, respectively. CONCLUSIONS: Empagliflozin 10 and 25 mg for 24 weeks as
      add-on to metformin therapy significantly improved glycemic control, weight, and
      BP, and were well-tolerated.

PMID- 24722495
TI  - Comparative effectiveness of peer leaders and community health workers in
      diabetes self-management support: results of a randomized controlled trial.
AB  - OBJECTIVE: To compare a peer leader (PL) versus a community health worker (CHW)
      telephone outreach intervention in sustaining improvements in HbA1c over 12
      months after a 6-month diabetes self-management education (DSME) program.
      RESEARCH DESIGN AND METHODS: One hundred and sixteen Latino adults with type 2
      diabetes were recruited from a federally qualified health center and randomized
      to (1) a 6-month DSME program followed by 12 months of weekly group sessions
      delivered by PLs with telephone outreach to those unable to attend or (2) a 6
      month DSME program followed by 12 months of monthly telephone outreach delivered
      by CHWs. The primary outcome was HbA1c. Secondary outcomes were cardiovascular
      disease risk factors, diabetes distress, and diabetes social support. Assessments
      were conducted at baseline, 6, 12, and 18 months. RESULTS: After DSME, the PL
      group achieved a reduction in mean HbA1c (8.2-7.5% or 66-58 mmol/mol, P < 0.0001)
      that was maintained at 18 months (-0.6% or -6.6 mmol/mol from baseline [P =
      0.009]). The CHW group also showed a reduction in HbA1c (7.8 vs. 7.3% or 62 vs.
      56 mmol/mol, P = 0.0004) post-6 month DSME; however, it was attenuated at 18
      months (-0.3% or -3.3 mmol/mol from baseline, within-group P = 0.234). Only the
      PL group maintained improvements achieved in blood pressure at 18 months. At the
      18-month follow-up, both groups maintained improvements in waist circumference,
      diabetes support, and diabetes distress, with no significant differences between
      groups. CONCLUSIONS: Both low-cost maintenance programs led by either a PL or a
      CHW maintained improvements in key patient-reported diabetes outcomes, but the PL
      intervention may have additional benefit in sustaining clinical improvements
      beyond 12 months.

PMID- 24722496
TI  - Can a selective PPARgamma modulator improve glycemic control in patients with
      type 2 diabetes with fewer side effects compared with pioglitazone?
AB  - OBJECTIVE: INT131 besylate is a potent, nonthiazolidinedione, selective
      peroxisome proliferator-activated receptor gamma (PPARgamma) modulator (SPPARM)
      designed to improve glucose metabolism while minimizing the side effects of full
      PPARgamma agonists. This placebo-controlled study compared the efficacy and side
      effects of INT131 besylate versus 45 mg pioglitazone HCl in subjects with type 2
      diabetes (T2D). RESEARCH DESIGN AND METHODS: This was a 24-week randomized,
      double-blind, placebo- and active-controlled study of 0.5-3.0 mg INT131 versus 45
      mg pioglitazone or placebo daily in 367 subjects with T2D on sulfonylurea or
      sulfonylurea plus metformin. The primary efficacy analysis was the comparison of
      change from baseline to week 24 in hemoglobin A1c (HbA1c) across treatment
      groups. Fluid status was assessed with a prospective scoring system for lower
      extremity pitting edema. RESULTS: INT131 had a steep dose response for efficacy
      as measured by changes in HbA1c. After 24 weeks' treatment, the 0.5-mg dose
      demonstrated minimal efficacy (HbA1c -0.3 +/- 0.12%) and the 2-mg dose
      demonstrated near-maximal efficacy (HbA1c -1.1 +/- 0.12%), which was not
      statistically different from the efficacy of 45 mg pioglitazone (HbA1c -0.9 +/-
      0.12%; P < 0.01 for noninferiority). With the 1-mg dose, INT131 provided
      significant improvements in glycemic control (HbA1c 0.8 +/- 0.12; P < 0.001 vs.
      placebo) but with less edema, weight gain, and hemodilution than observed with 45
      mg pioglitazone. CONCLUSIONS: INT131 demonstrated dose-dependent reductions in
      HbA1c, equivalent to 45 mg pioglitazone, but with less fluid accumulation and
      weight gain, consistent with its SPPARM design.

PMID- 24722497
TI  - The effects of a Mediterranean diet on the need for diabetes drugs and remission
      of newly diagnosed type 2 diabetes: follow-up of a randomized trial.
AB  - OBJECTIVE: To assess the long-term effects of dietary interventions on glycemic
      control, need for diabetes medications, and remission of type 2 diabetes.
      RESEARCH DESIGN AND METHODS: Originally, in a two-arm trial design, overweight,
      middle-aged men and women with newly diagnosed type 2 diabetes were randomized to
      a low-carbohydrate Mediterranean diet (LCMD; n = 108) or a low-fat diet (n =
      107). After 4 years, participants who were still free of diabetes medications
      were further followed up until the primary end point (need of a diabetic drug);
      remission of diabetes (partial or complete) and changes in weight, glycemic
      control, and cardiovascular risk factors were also evaluated. RESULTS: The
      primary end point was reached in all participants after a total follow-up of 6.1
      years in the low-fat group and 8.1 years in the LCMD group; median survival time
      was 2.8 years (95% CI 2.4-3.2) and 4.8 years (4.3-5.2), respectively. The
      unadjusted hazard ratio for the overall follow-up was 0.68 (0.50-0.89; P <
      0.001). LCMD participants were more likely to experience any remission (partial
      or complete), with a prevalence of 14.7% (13.0-16.5%) during the first year and
      5.0% (4.4-5.6%) during year 6 compared with 4.1% (3.1-5.0%) at year 1 and 0% at
      year 6 in the low-fat diet group. CONCLUSIONS: In patients with newly diagnosed
      type 2 diabetes, an LCMD resulted in a greater reduction of HbA1c levels, higher
      rate of diabetes remission, and delayed need for diabetes medication compared
      with a low-fat diet.

PMID- 24722498
TI  - LADA and CARDS: a prospective study of clinical outcome in established adult
      onset autoimmune diabetes.
AB  - OBJECTIVE: Diabetes-associated autoantibodies can be detected in adult-onset
      diabetes, even when initially non-insulin requiring, i.e., with latent autoimmune
      diabetes. We aimed to identify adult-onset autoimmune diabetes in patients with
      established "type 2 diabetes" participating in the Collaborative Atorvastatin
      Diabetes Study (CARDS) to characterize their phenotype and clinical outcome.
      RESEARCH DESIGN AND METHODS: We prospectively studied 2,425 European patients
      with presumed type 2 diabetes (mean age 62 years, diabetes duration 7.9 years)
      for outcomes at 3.9 years after randomization to either atorvastatin or placebo.
      Subjects were screened for autoantibodies to GAD (GADA), insulinoma-associated
      antigen-2 (IA-2A), and zinc-transporter 8 (ZnT8A). RESULTS: A total of 173
      patients (7.1%) had GADA, of whom 11 (0.5%) and 5 (0.2%) were also positive for
      IA-2A and ZnT8A, respectively. At baseline, 44% of GADA-positive patients were
      not on insulin. Fewer autoantibody-positive than autoantibody-negative patients
      had metabolic syndrome (64 vs. 80%), and more were on insulin (56 vs. 17%) (P <
      0.0001 for each) without lower HbA1c (69 mmol/mol [8.5%] vs. 62 mmol/mol [7.8%]).
      The frequency of microvascular and macrovascular events was similar in both
      cohorts, independent of atorvastatin. CONCLUSIONS: Adult-onset autoimmune
      diabetes was prevalent, even in patients with established diabetes presumed to
      have type 2 diabetes. After 11.8 years' diabetes duration, nearly half the
      patients with autoimmune diabetes were not on insulin treatment and almost two
      thirds had metabolic syndrome. The type of diabetes, whether autoimmune diabetes
      or type 2 diabetes, did not impact the risk of microvascular disease.

PMID- 24722500
TI  - The efficacy and safety of imeglimin as add-on therapy in patients with type 2
      diabetes inadequately controlled with sitagliptin monotherapy.
AB  - OBJECTIVE: This 12-week study assessed the efficacy and tolerability of imeglimin
      as add-on therapy to the dipeptidyl peptidase-4 inhibitor sitagliptin in patients
      with type 2 diabetes inadequately controlled with sitagliptin monotherapy.
      RESEARCH DESIGN AND METHODS: In a multicenter, randomized, double-blind, placebo
      controlled, parallel-group study, imeglimin (1,500 mg b.i.d.) or placebo was
      added to sitagliptin (100 mg q.d.) over 12 weeks in 170 patients with type 2
      diabetes (mean age 56.8 years; BMI 32.2 kg/m(2)) that was inadequately controlled
      with sitagliptin alone (A1C >=7.5%) during a 12-week run-in period. The primary
      efficacy end point was the change in A1C from baseline versus placebo; secondary
      end points included corresponding changes in fasting plasma glucose (FPG) levels,
      stratification by baseline A1C, and percentage of A1C responders. RESULTS:
      Imeglimin reduced A1C levels (least-squares mean difference) from baseline (8.5%)
      by 0.60% compared with an increase of 0.12% with placebo (between-group
      difference 0.72%, P < 0.001). The corresponding changes in FPG were -0.93 mmol/L
      with imeglimin vs. -0.11 mmol/L with placebo (P = 0.014). With imeglimin, the A1C
      level decreased by >=0.5% in 54.3% of subjects vs. 21.6% with placebo (P <
      0.001), and 19.8% of subjects receiving imeglimin achieved a decrease in A1C
      level of <=7% compared with subjects receiving placebo (1.1%) (P = 0.004).
      Imeglimin was generally well tolerated, with a safety profile comparable to
      placebo and no related treatment-emergent adverse events. CONCLUSIONS: Imeglimin
      demonstrated incremental efficacy benefits as add-on therapy to sitagliptin, with
      comparable tolerability to placebo, highlighting the potential for imeglimin to
      complement other oral antihyperglycemic therapies.

PMID- 24722499
TI  - Dietary protein intake and incidence of type 2 diabetes in Europe: the EPIC
      InterAct Case-Cohort Study.
AB  - OBJECTIVE: The long-term association between dietary protein and type 2 diabetes
      incidence is uncertain. We aimed to investigate the association between total,
      animal, and plant protein intake and the incidence of type 2 diabetes. RESEARCH
      DESIGN AND METHODS: The prospective European Prospective Investigation into
      Cancer and Nutrition (EPIC)-InterAct case-cohort study consists of 12,403
      incident type 2 diabetes cases and a stratified subcohort of 16,154 individuals
      from eight European countries, with an average follow-up time of 12.0 years.
      Pooled country-specific hazard ratios (HRs) and 95% CI of prentice-weighted Cox
      regression analyses were used to estimate type 2 diabetes incidence according to
      protein intake. RESULTS: After adjustment for important diabetes risk factors and
      dietary factors, the incidence of type 2 diabetes was higher in those with high
      intake of total protein (per 10 g: HR 1.06 [95% CI 1.02-1.09], P(trend) < 0.001)
      and animal protein (per 10 g: 1.05 [1.02-1.08], P(trend) = 0.001). Effect
      modification by sex (P < 0.001) and BMI among women (P < 0.001) was observed.
      Compared with the overall analyses, associations were stronger in women, more
      specifically obese women with a BMI >30 kg/m(2) (per 10 g animal protein: 1.19
      [1.09-1.32]), and nonsignificant in men. Plant protein intake was not associated
      with type 2 diabetes (per 10 g: 1.04 [0.93-1.16], P(trend) = 0.098). CONCLUSIONS:
      High total and animal protein intake was associated with a modest elevated risk
      of type 2 diabetes in a large cohort of European adults. In view of the rapidly
      increasing prevalence of type 2 diabetes, limiting iso-energetic diets high in
      dietary proteins, particularly from animal sources, should be considered.

PMID- 24722501
TI  - CHIP is a novel tumor suppressor in pancreatic cancer through targeting EGFR.
AB  - Carboxyl terminus of heat shock protein 70-interacting protein (CHIP) is an E3
      ubiquitin ligase that is involved in protein quality control and mediates several
      tumor-related proteins in many cancers, but the function of CHIP in pancreatic
      cancer is not known. Here we show that CHIP interacts and ubiquitinates epidermal
      growth factor receptor (EGFR) for proteasome-mediated degradation in pancreatic
      cancer cells, thereby inhibiting the activation of EGFR downstream pathway. CHIP
      suppressed cell proliferation, anchor-independent growth, invasion and migration,
      as well as enhanced apoptosis induced by erlotinib in vitro and in vivo. The
      expression of CHIP was decreased in pancreatic cancer tissues or sera. Low CHIP
      expression in tumor tissues was correlated with tumor differentiation and shorter
      overall survival. These observations indicate that CHIP serves as a novel tumor
      suppressor by down-regulating EGFR pathway in pancreatic cancer cells, decreased
      expression of CHIP was associated with poor prognosis in pancreatic cancer. 

PMID- 24722502
TI  - Enhanced antibacterial activity of silver nanoparticles/halloysite
      nanotubes/graphene nanocomposites with sandwich-like structure.
AB  - A sandwich-like antibacterial reagent (Ag/HNTs/rGO) was constructed through the
      direct growth of silver nanoparticles on the surface graphene-based HNTs
      nanosheets. Herein, various nanomaterials were combined by adhesion effect of
      DOPA after self-polymerization. Ag/HNTs/rGO possess enhanced antibacterial
      ability against E. coli and S. aureus compared with individual silver
      nanoparticles, rGO nanosheets or their nanocomposites.

PMID- 24722503
TI  - Reply to 'Patient experience of the transition from Xalatan to generic
      latanoprost'.

PMID- 24722504
TI  - Switch of anti-VEGF agents is an option for nonresponders in the treatment of
      AMD.
AB  - BACKGROUND: Although anti-VEGF therapy of exudative AMD with bevacizumab and
      ranibizumab proved efficacious in the majority of patients, CNV activity does not
      respond to continued treatment after repeated injections in a considerable amount
      of patients. These are referred to as nonresponders. A change of the drug to
      bevacizumab or ranibizumab could possibly offer an alternative option for the
      treatment of nonresponding exudative AMD. METHODS AND MATERIALS: A total of 138
      nonresponders who switched therapy from bevacizumab to ranibizumab (n=114) or
      vice versa (n=24) were included in a retrospective study. Visual acuity (VA) and
      foveal thickness before and after the switch of therapy were compared. By means
      of linear regression analysis, we analyzed possible prognostic factors associated
      with a favorable outcome for visual acuity. RESULTS: Linear regression analysis
      revealed a statistically significant benefit for nonresponders when treatment was
      changed to a different anti-VEGF drug (bevacizumab or ranibizumab). VA at the
      time of the switch was positively correlated with a beneficial development of VA
      after changing the drug. There was no significant correlation with age, macular
      thickness, number of injections before the switch, or the development of VA under
      treatment before the switch. Both patients switching to Avastin and Lucentis
      benefitted without statistically significant differences. CONCLUSIONS: An
      exchange of bevacizumab with ranibizumab or vice versa should be considered in
      nonresponders in the treatment of exudative AMD. Further prognostic factors may
      help to identify patients who might benefit from a switch. These factors should
      be investigated in further studies.

PMID- 24722505
TI  - The surgical approach to the management of anterior uveal melanomas.
AB  - PURPOSE: Surgical excision of peripheral iris or ciliary body melanomas can be
      performed antero-posteriorly (irido-cyclectomy) with mydriasis or postero
      anteriorly (cyclo-iridectomy) with miosis. The aim of this study was to evaluate
      the results of both surgical techniques. METHODS: Patients were enrolled in the
      study if they underwent irido-cyclectomy or cyclo-iridectomy for iris and/or
      ciliary body melanoma at the Liverpool Ocular Oncology Centre between 1993 and
      2012. RESULTS: The 24 patients (8 male, 16 female) had a median age of 57 years.
      The largest median basal tumour diameter and the median tumour thickness were 4.8
      and 2.2 mm, respectively. The resection was performed antero-posteriorly in 9
      (37%) patients and postero-anteriorly or circumferentially in 15 (63%). Nine
      tumours contained epithelioid cells. Genetic studies were performed in 10
      patients, showing chromosome 3 loss in two. Postoperative complications included
      hypotony in 9 (37%) patients, cataract in 8 (33%), hyphaema in 8 (33%),
      cyclodialysis in 1 (4%), wound dehiscence in 1 (4%) and bullous keratopathy in 1
      patient (4%). The median follow-up time was 2.4 years. The last known visual
      acuity was 6/6-6/12 in 20 (91%) patients and 6/18-6/60 in 2 (9%), with 2 (8%)
      requiring secondary enucleation. Local tumour recurrence developed in 1 patient
      (4%). Two (8%) patients died of metastatic disease. CONCLUSIONS: Surgical
      resection of peripheral iris melanomas achieves high rates of visual conservation
      and local tumour control and may be the preferred option when tissue is required
      for laboratory studies.

PMID- 24722506
TI  - Patient experience of the transition from Xalatan to generic latanoprost.

PMID- 24722507
TI  - The Epigenome View: An Effort towards Non-Invasive Prenatal Diagnosis.
AB  - Epigenetic modifications have proven to play a significant role in cancer
      development, as well as fetal development. Taking advantage of the knowledge
      acquired during the last decade, great interest has been shown worldwide in
      deciphering the fetal epigenome towards the development of methylation-based non
      invasive prenatal tests (NIPT). In this review, we highlight the different
      approaches implemented, such as sodium bisulfite conversion, restriction enzyme
      digestion and methylated DNA immunoprecipitation, for the identification of
      differentially methylated regions (DMRs) between free fetal DNA found in maternal
      blood and DNA from maternal blood cells. Furthermore, we evaluate the use of
      selected DMRs identified towards the development of NIPT for fetal chromosomal
      aneuploidies. In addition, we perform a comparison analysis, evaluate the
      performance of each assay and provide a comprehensive discussion on the potential
      use of different methylation-based technologies in retrieving the fetal
      methylome, with the aim of further expanding the development of NIPT assays. 

PMID- 24722508
TI  - The effects of stress at work and at home on inflammation and endothelial
      dysfunction.
AB  - This study examined whether stress at work and at home may be related to
      dysregulation of inflammation and endothelial function, two important
      contributors to the development of cardiovascular disease. In order to explore
      potential biological mechanisms linking stress with cardiovascular health, we
      investigated cross-sectional associations between stress at work and at home with
      an inflammation score (n's range from 406-433) and with two endothelial
      biomarkers (intercellular and vascular adhesion molecules, sICAM-1 and sVCAM-1;
      n's range from 205-235) in a cohort of healthy US male health professionals. No
      associations were found between stress at work or at home and inflammation. Men
      with high or medium levels of stress at work had significantly higher levels of
      sVCAM-1 (13% increase) and marginally higher levels of sICAM-1 (9% increase),
      relative to those reporting low stress at work, independent of health behaviors.
      Men with high levels of stress at home had marginally higher levels of both sVCAM
      1 and sICAM-1 than those with low stress at home. While lack of findings related
      to inflammation are somewhat surprising, if replicated in future studies, these
      findings may suggest that endothelial dysfunction is an important biological
      mechanism linking stress at work with cardiovascular health outcomes in men. 

PMID- 24722511
TI  - On reliability.

PMID- 24722509
TI  - Uncoupling transcription from covalent histone modification.
AB  - It is widely accepted that transcriptional regulation of eukaryotic genes is
      intimately coupled to covalent modifications of the underlying chromatin
      template, and in certain cases the functional consequences of these modifications
      have been characterized. Here we present evidence that gene activation in the
      silent heterochromatin of the yeast Saccharomyces cerevisiae can occur in the
      context of little, if any, covalent histone modification. Using a SIR-regulated
      heat shock-inducible transgene, hsp82-2001, and a natural drug-inducible
      subtelomeric gene, YFR057w, as models we demonstrate that substantial
      transcriptional induction (>200-fold) can occur in the context of restricted
      histone loss and negligible levels of H3K4 trimethylation, H3K36 trimethylation
      and H3K79 dimethylation, modifications commonly linked to transcription
      initiation and elongation. Heterochromatic gene activation can also occur with
      minimal H3 and H4 lysine acetylation and without replacement of H2A with the
      transcription-linked variant H2A.Z. Importantly, absence of histone modification
      does not stem from reduced transcriptional output, since hsp82-DeltaTATA, a
      euchromatic promoter mutant lacking a TATA box and with threefold lower induced
      transcription than heterochromatic hsp82-2001, is strongly hyperacetylated in
      response to heat shock. Consistent with negligible H3K79 dimethylation, dot1Delta
      cells lacking H3K79 methylase activity show unimpeded occupancy of RNA polymerase
      II within activated heterochromatic promoter and coding regions. Our results
      indicate that large increases in transcription can be observed in the virtual
      absence of histone modifications often thought necessary for gene activation. 

PMID- 24722512
TI  - Impact of vacuum-assisted closure therapy on outcomes of sternal wound
      dehiscence?.
AB  - OBJECTIVES: Sternal wound dehiscence (SWD) after cardiac surgery is a rare but
      serious condition associated with considerable costs and morbidity. We sought to
      evaluate the results of the introduction of vacuum-assisted closure (VAC) therapy
      in the management of sternal wound dehiscence, compared with those of previous
      conventional treatments. METHODS: We retrospectively collected 7148 patients who
      underwent cardiac surgery at our institution between January 2002 and June 2012.
      A total of 152 (2.1%) patients had a sternal wound dehiscence: 107 were treated
      with conventional treatments (Group A) and 45 were managed with VAC therapy
      (Group B). Patients were stratified according to preoperative risk factors and
      type of sternal wound dehiscence (superficial or deep; infected or not) and
      compared by means of a propensity-matched analysis. A cost analysis was also
      performed. RESULTS: Forty-five patients of each group matched for all
      preoperative risk factors and type of sternal wound dehiscence. SWD-related
      mortality rate was significantly lower in Group B (11 vs 0%; P = 0.05). Incidence
      of mediastinitis (P < 0.0001), sepsis (P = 0.04), delayed SWD infection (P =
      0.05), other complication (P = 0.05), surgical sternal revision (P = 0.04) and
      surgical superficial revision (P < 0.0001) were all significantly lower in Group
      B. Mean patient cost was 31 106? in Group A and 24 383? in Group B, thus
      achieving a mean saving of 6723? per patient. CONCLUSIONS: In our experience, the
      use of VAC therapy for the management of SWD was considerably effective in
      decreasing mortality (SWD related), incidence of complications and need for
      surgical procedures; thus, leading to a significant reduction of costs.

PMID- 24722513
TI  - A need for speed? Bypass time and outcomes after isolated aortic valve
      replacement surgery.
AB  - OBJECTIVES: To determine in the modern era if cardiopulmonary bypass (CPB) time
      has a significant effect on postoperative morbidity, mortality and long-term
      survival in patients undergoing isolated aortic valve replacement (AVR) surgery.
      METHODS: Analysis of a prospectively collected cardiac surgery database was
      performed. Uni- and multivariate analysis on the need of resternotomy for
      bleeding, mediastinal blood loss, intensive care unit (ICU) length of stay,
      hospital length of stay, in-hospital mortality and long- term survival was
      performed. Only patients with a cross-clamp time <90 min were analysed to exclude
      technical issues confounding the results. RESULTS: A total of 1863 isolated first
      time AVR procedures were analysed, with an in-hospital mortality rate of 2.4%.
      The rate of long-term follow-up achieved was 100%. Univariate analysis revealed
      that CPB time (minutes) had no significant effect on resternotomy (P = 0.5),
      creatinine kinase muscle-brain isoenzyme (CKMB) release (P = 0.8) and long-term
      survival (P = 0.06), but was significantly associated with mediastinal blood loss
      (P = 0.01), ICU length of stay (P = 0.02), hospital length of stay (P = 0.03) and
      in-hospital mortality (P < 0.001). Multivariate analysis identified that bypass
      time (min) was a significant factor associated with mediastinal blood loss (P <
      0.001), ICU length of stay (P = 0.01), postoperative length of stay (P < 0.001)
      and in-hospital mortality (odds ratio [OR] 1.02, 95% CI 1.01-1.04, P = 0.01), but
      not long-term survival. Multivariate analysis identified that era of surgery had
      no significant effect on CKMB release (P = 0.2), mediastinal blood loss (P = 0.4)
      and in-hospital mortality (P = 0.9), but the latter era of this study was
      significantly associated with a reduced postoperative length of stay (P < 0.001),
      reduced ICU length of stay (P < 0.001), reduced need for resternotomy for
      bleeding (OR 0.62, 95% CI 0.41-0.94, P = 0.02) and improved long-term survival
      (hazard ratio 0.76, 95% CI 0.59-0.96, P = 0.02). Adjusting for era made no
      difference with respect to the above study findings. CONCLUSIONS: Despite
      improvements over time with regard to morbidity, mortality and long-term
      survival, CPB time remains a significant factor determining mediastinal blood
      loss, ICU and hospital length of stay, and in-hospital mortality.

PMID- 24722514
TI  - Pulsatile mode of operation of left ventricular assist devices and pulmonary
      haemodynamics.
AB  - OBJECTIVES: To determine the effect of differing modes of left ventricular assist
      device (LVAD) operation: synchronous, independent (asynchronous or
      pseudosynchronous) or counter pulsation (antisynchronous), on left atrial
      pressure, pulmonary artery pressure, pulmonary blood flow and right ventricular
      work load, utilizing a previously published electrical analogy of the systemic
      and pulmonary circulation and the heart. METHODS: A previously published
      electrical analogy of the systemic and pulmonary circulation was utilized. The
      Simulation Package with Integrated Circuit Emphasis (LTSPICE IV) was utilized.
      Three LVAD operation mode scenarios were analysed: synchronous, counter pulsation
      and independent pulsatile. The root mean square of the pulmonary artery pressure
      (PAP), left atrial pressure (LAP) and pulmonary blood flow (PBF) were calculated,
      as was the right ventricular work load. RESULTS: Counter pulsation LVAD operation
      resulted in the lowest LAP, PAP, right ventricular work load and the highest
      pulmonary blood flow. Independent pulsation resulted in the highest LAP, PAP and
      the lowest pulmonary blood flow. This technique actually increased RV work load.
      CONCLUSIONS: If an LVAD is to be operated in a pulsatile mode, the counter
      pulsation mode reduces pulmonary artery and left atrial pressure and increases
      pulmonary blood flow and thus cardiac output. This is in addition to the reduced
      right ventricular energetic requirement, a finding previously described. Clinical
      validation of our findings is necessary.

PMID- 24722515
TI  - Ventricular remodelling after pulmonary valve replacement: comparison between
      pressure-loaded and volume-loaded right ventricles.
AB  - OBJECTIVES: In patients with severe pulmonary valve regurgitation or stenosis,
      pulmonary valve replacement (PVR) has a favourable effect on right ventricular
      (RV) volume and pressure unloading. PVR thereby decreases the progression of RV
      dilatation and/or hypertrophy. This study investigates RV remodelling patterns
      after PVR in patients with either pressure, volume or combined volume- and
      pressure-loaded RVs. METHODS: We evaluated 79 consecutive patients who had
      undergone PVR, between 1999 and 2012 beyond the age of 14 years. Comparisons were
      made according to the RV loading condition, i.e. isolated volume-loaded (iPR, n =
      53), combined volume- and pressure-loaded (cPR/[PS] pulmonary stenosis, n = 16),
      and isolated pressure-loaded RVs (iPS n = 10). The main study outcome was the
      change of the RV end-diastolic diameter (DeltaRVEDD) before and after PVR,
      measured on echocardiography. RESULTS: The majority of patients (65%) had a
      tetralogy of Fallot. After PVR, the RVEDD decreased with 5.3 mm/m(2), body
      surface area (BSA) (P < 0.001). In addition, the RV end-diastolic volume on
      cardiac magnetic resonance declines with 40 ml/m(2), BSA (P < 0.001). The change
      in the RVEDD after PVR was different according to the loading condition (i.e.
      iPR: -6.6, cPR/PS: -4.7 and iPS: +0.4 mm/m(2), P < 0.001). In a multivariate
      regression model, pressure load remained a significant predictor of decreased
      RVEDD (P = 0.005). CONCLUSIONS: The current data indicate that the type of right
      ventricular loading (pressure versus volume) before PVR affects the RV
      remodelling pattern after PVR. Right ventricular pressure load has an adverse
      effect on early RV remodelling after PVR.

PMID- 24722516
TI  - Might digital drains speed up the time to thoracic drain removal?
AB  - A best evidence topic in thoracic surgery was written according to a structured
      protocol. The question addressed was: might digital drains speed up the time to
      thoracic drain removal in terms of time till chest drain removal, hospital stay
      and overall cost? A total of 296 papers were identified as a result of the search
      as described below. Of these, five papers provided 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 the
      papers are tabulated. A literature search revealed that several single-centre
      prospective randomized studies have shown significantly earlier removal of chest
      drains with digital drains ranging between 0.8 and 2.1 days sooner. However,
      there was heterogeneity in studies in the management protocol of chest drains in
      terms of the use of suction, number of drains and assessment for drain removal.
      Some protocols such as routinely keeping drains irrespective of the presence of
      air leak or drain output may have skewed results. Differences in exclusion
      criteria and protocols for discharging home with portable devices may have biased
      results. Due to heterogeneity in the management protocol of chest drains, there
      is conflicting evidence regarding hospital stay. The limited data on cost suggest
      that there may be significantly lower postoperative costs in the digital drain
      group. All the studies were single-centre series generally including patients
      with good preoperative lung function tests. Further larger studies with more
      robust chest drain management protocols are required especially to assess length
      of hospital stay, cost and whether the results are applicable to a larger patient
      population. 

PMID- 24722517
TI  - In patients with resectable non-small-cell lung cancer, is video-assisted
      thoracoscopic segmentectomy a suitable alternative to thoracotomy and
      segmentectomy in terms of morbidity and equivalence of resection?
AB  - A best evidence topic in cardiac surgery was written according to a structured
      protocol. The question addressed was 'In patients with resectable non-small-cell
      lung cancer, is video-assisted thoracoscopic segmentectomy a suitable alternative
      to thoracotomy and segmentectomy in terms of morbidity and equivalence of
      resection?' Altogether 232 papers were found as a result of the reported search,
      of which 7 represented the best evidence to answer the clinical question. The
      authors, journal, date and country of publication, patient group studied, study
      type, relevant outcomes and results of these papers are tabulated. Only one study
      compared the survival rates of video-assisted thoracoscopic surgery (VATS) and
      open surgery and found no significant difference in overall (P = 0.605) and
      disease-free (P = 0.996) survival between these groups. The mean length of
      hospital stay was reported as shorter following VATS when compared with open
      surgery in all of the studies looking at this outcome. The greatest difference in
      length of hospital stay reported was 4.8 days (VATS 3.5 days and open 8.3 days).
      The duration of chest tube placement was also universally reported as shorter in
      patients having VATS procedures when compared with open procedures. Two studies
      compared the number of lymph nodes that could be sampled when completing this
      operation by VATS using an open approach and neither found there to be a
      significant difference between these numbers. Using the evidence collected, we
      conclude that anatomical segmentectomy performed by VATS is a safe and effective
      alternative to conventional techniques in the surgical management of non-small
      cell lung cancer. We are aware that the current evidence is limited and existing
      studies all examine small numbers of patients. Unfortunately, at present there is
      no blinded randomized control trial comparing these two surgical methods. There
      is also no study comparing the utility of each method for differing anatomical
      locations of segments. This should be kept in mind when interpreting the results
      of the studies presented. 

PMID- 24722518
TI  - A novel procedure for reconstruction utilizing superficial femoral vein grafts
      following en bloc resection of carotid artery and head and neck malignant
      tumours.
AB  - OBJECTIVES: The objective of our study was to investigate the effectiveness of
      reconstructing the carotid artery using a superficial femoral vein (SFV).
      METHODS: Ten patients with malignant tumours involving the carotid artery
      underwent carotid artery resection and reconstruction with the SFV. We use the
      SFV between the deep femoral vein and perforator branches to the great saphenous
      vein or deep femoral vein at the popliteal region reconstructive vessel. RESULTS:
      The mean length and diameter of the grafted SFVs were 13.9 and 11.2 mm,
      respectively. The mean time for SFV acquirement was 18 min. The mean cerebral
      ischaemic period was 23.1 min. Nine patients did not experience any neurological
      complications. One patient experienced slight temporary hemiparesis. There was no
      postoperative vascular graft thrombosis. Donor site complications did not occur.
      CONCLUSIONS: Reconstructing the carotid artery using an SFV is very effective due
      to the ease in harvesting the vessel and its optimal size and length for carotid
      artery replacement.

PMID- 24722519
TI  - Atrial apoptosis and fibrosis adversely affect atrial conduit, reservoir and
      contractile functions.
AB  - OBJECTIVES: Chronic atrial volume overload and atrial fibrillation (AF) induce
      structural changes within atrial myocardium. The aim of this study was to
      evaluate the effect of adverse cellular remodelling on echocardiographic strain
      rate (SR) deformation indices of atrial contractile, conduit and reservoir
      functions. METHODS: Forty-four consecutive patients with organic mitral
      regurgitation were analysed. Twenty-eight patients had long-standing persistent
      AF (AF group), while 16 were in normal sinus rhythm (NSR group). Left atrial (LA)
      samples were harvested from all the patients for histological analysis.
      Postoperative echocardiographic data acquisition was performed exclusively during
      organized atrial electrical activity in order to assess the contractile reserve
      of patients from both groups. RESULTS: Fibrotic atria had inferior conduit (SR-E:
      r = -0.36, P = 0.017), reservoir (SR-S: r = -0.31, P = 0.041) and contractile
      functions (SR-A: r = -0.33, P = 0.027). Analogously, atria with greater apoptotic
      burdens showed a negative correlation with multiple indices of left atrial
      functions (SR-E: r = -0.38, P = 0.010; SR-S: r = -0.33, P = 0.028; SR-A: r = 
      0.28, P = 0.067). The efficiency of atrial contractility was significantly
      reduced among AF-group patients after conversion to sinus rhythm, when compared
      with patients in the NSR group (LA active emptying fraction: 20 +/- 12 vs 30 +/-
      10%, P = 0.004; SR-A: 1.1 +/- 1.0 vs 2.8 +/- 1.9 s(-1), P < 0.001). Superior
      strain-rate indices of atrial conduit and reservoir functions were noted in the
      NSR group (SR-E: 3.5 +/- 2.3 vs 1.3 +/- 1.0 s(-1), P < 0.001; LA expansion index:
      86 +/- 31 vs 60 +/- 42%, P = 0.004). Fibrosis was evident in 7.2 [3.3;9.4]% of
      the LA tissue sample in the AF group, while it accounted for 3.4 [1.2;8.1]% of
      atrial tissue in the NSR group (P = 0.054). Apoptosis was documented in 13 (46%)
      patients in the AF group, whereas none of the patients in the NSR group exhibited
      signs of programmed cell death (P = 0.001). Myocyte degeneration was more
      prevalent in the AF group (odds ratio: 7.0, 95% confidence interval: 1.3-36.7, P
      = 0.021). Age showed a positive correlation with worsening degrees of atrial
      fibrosis and apoptosis (r = 0.41, P = 0.006; r = 0.49, P = 0.001, respectively).
      Multiple regression analysis identified SR-S (beta = -1.263, P = 0.036) and age
      (beta = 0.144, P = 0.057) as independent predictors of fibrosis. Independent
      determinants of apoptosis were preoperative AF (beta = 4.539, P = 0.007), age
      (beta = 0.188, P = 0.009) and SR-S (beta = -1.780, P = 0.002). CONCLUSIONS: Atria
      exhibiting greater fibrotic and apoptotic burdens had impaired conduit, reservoir
      and contractile function, as evaluated by deformation imaging. Among patients
      with chronic LA volume overload, exposure to long-standing persistent AF induced
      more pronounced degrees of adverse atrial cellular remodelling. Strain-rate
      descriptors of atrial reservoir function harboured potential to predict atrial
      fibrosis and apoptosis.

PMID- 24722520
TI  - Mechanisms influencing the spread of a native marine alga.
AB  - Like invasive macrophytes, some native macrophytes are spreading rapidly with
      consequences for community structure. There is evidence that the native alga
      Caulerpa filiformis is spreading along intertidal rocky shores in New South
      Wales, Australia, seemingly at the expense of native Sargassum spp. We
      experimentally investigated the role physical disturbance plays in the spread of
      C. filiformis and its possible consequences for Sargassum spp. Cleared patches
      within beds of C. filiformis (Caulerpa habitat) or Sargassum spp. (Sargassum
      habitat) at multiple sites showed that C. filiformis had significantly higher
      recruitment (via propagules) into its own habitat. The recruitment of Sargassum
      spp. to Caulerpa habitat was rare, possibly due in part to sediment accretion
      within Caulerpa habitat. Diversity of newly recruited epibiotic assemblages
      within Caulerpa habitat was significantly less than in Sargassum habitat. In
      addition, more C. filiformis than Sargassum spp. recruited to Sargassum habitat
      at some sites. On common boundaries between these two macroalgae, the vegetative
      growth of adjacent C. filiformis into cleared patches was significantly higher
      than for adjacent Sargassum spp. In both experiments, results were largely
      independent of the size of disturbance (clearing). Lastly, we used PAM
      fluorometry to show that the photosynthetic condition of Sargassum spp. fronds
      adjacent to C. filiformis was generally suppressed relative to those distant from
      C. filiformis. Thus, physical disturbance, combined with invasive traits (e.g.
      high levels of recruitment and vegetative growth) most likely facilitate the
      spread of C. filiformis, with the ramifications being lower epibiotic diversity
      and possibly reduced photosynthetic condition of co-occurring native macrophytes.

PMID- 24722521
TI  - Broadband antireflection and light extraction enhancement in fluorescent SiC with
      nanodome structures.
AB  - We demonstrate a time-efficient and low-cost approach to fabricate Si3N4 coated
      nanodome structures in fluorescent SiC. Nanosphere lithography is used as the
      nanopatterning method and SiC nanodome structures with Si3N4 coating are formed
      via dry etching and thin film deposition process. By using this method, a
      significant broadband surface antireflection and a considerable omnidirectional
      luminescence enhancement are obtained. The experimental observations are then
      supported by numerical simulations. It is believed that our fabrication method
      will be well suitable for large-scale production in the future. 

PMID- 24722522
TI  - Insight into the interactions between novel isoquinolin-1,3-dione derivatives and
      cyclin-dependent kinase 4 combining QSAR and molecular docking.
AB  - Several small-molecule CDK inhibitors have been identified, but none have been
      approved for clinical use in the past few years. A new series of 4-[(3
      hydroxybenzylamino)-methylene]-4H-isoquinoline-1,3-diones were reported as highly
      potent and selective CDK4 inhibitors. In order to find more potent CDK4
      inhibitors, the interactions between these novel isoquinoline-1,3-diones and
      cyclin-dependent kinase 4 was explored via in silico methodologies such as 3D
      QSAR and docking on eighty-one compounds displaying potent selective activities
      against cyclin-dependent kinase 4. Internal and external cross-validation
      techniques were investigated as well as region focusing, bootstraping and leave
      group-out. A training set of 66 compounds gave the satisfactory CoMFA model (q2 =
      0.695, r2 = 0.947) and CoMSIA model (q2 = 0.641, r2 = 0.933). The remaining 15
      compounds as a test set also gave good external predictive abilities with r2pred
      values of 0.875 and 0.769 for CoMFA and CoMSIA, respectively. The 3D-QSAR models
      generated here predicted that all five parameters are important for activity
      toward CDK4. Surflex-dock results, coincident with CoMFA/CoMSIA contour maps,
      gave the path for binding mode exploration between the inhibitors and CDK4
      protein. Based on the QSAR and docking models, twenty new potent molecules have
      been designed and predicted better than the most active compound 12 in the
      literatures. The QSAR, docking and interactions analysis expand the structure
      activity relationships of constrained isoquinoline-1,3-diones and contribute
      towards the development of more active CDK4 subtype-selective inhibitors. 

PMID- 24722524
TI  - Combined inflammatory and metabolic defects reflected by reduced serum protein
      levels in patients with Buruli ulcer disease.
AB  - Buruli ulcer is a skin disease caused by Mycobacterium ulcerans that is spreading
      in tropical countries, with major public health and economic implications in West
      Africa. Multi-analyte profiling of serum proteins in patients and endemic
      controls revealed that Buruli ulcer disease down-regulates the circulating levels
      of a large array of inflammatory mediators, without impacting on the leukocyte
      composition of peripheral blood. Notably, several proteins contributing to acute
      phase reaction, lipid metabolism, coagulation and tissue remodelling were also
      impacted. Their down-regulation was selective and persisted after the elimination
      of bacteria with antibiotic therapy. It involved proteins with various functions
      and origins, suggesting that M. ulcerans infection causes global and chronic
      defects in the host's protein metabolism. Accordingly, patients had reduced
      levels of total serum proteins and blood urea, in the absence of signs of
      malnutrition, or functional failure of liver or kidney. Interestingly, slow
      healers had deeper metabolic and coagulation defects at the start of antibiotic
      therapy. In addition to providing novel insight into Buruli ulcer pathogenesis,
      our study therefore identifies a unique proteomic signature for this disease. 

PMID- 24722526
TI  - Multiple Modes of Communication between Neurons and Oligodendrocyte Precursor
      Cells.
AB  - The surprising discovery of bona fide synapses between neurons and
      oligodendrocytes precursor cells (OPCs) 15 years ago placed these progenitors as
      real partners of neurons in the CNS. The role of these synapses has not been
      established yet, but a main hypothesis is that neuron-OPC synaptic activity is a
      signaling pathway controlling OPC proliferation/differentiation, influencing the
      myelination process. However, new evidences describing non-synaptic mechanisms of
      communication between neurons and OPCs have revealed that neuron-OPC interactions
      are more complex than expected. The activation of extrasynaptic receptors by
      ambient neurotransmitter or local spillover and the ability of OPCs to sense
      neuronal activity through a potassium channel suggest that distinct modes of
      communication mediate different functions of OPCs in the CNS. This review
      discusses different mechanisms used by OPCs to interact with neurons and their
      potential roles during postnatal development and in brain disorders. 

PMID- 24722527
TI  - Recurrent disease in juvenile differentiated thyroid carcinoma: prognostic
      factors, treatments, and outcomes.
AB  - The overall prognosis in pediatric differentiated thyroid carcinoma (DTC) is
      excellent. Recurrent disease is frequent, however, and requires additional
      treatment. We analyzed the probability of recurrence, prognostic factors,
      treatment, and outcome of juvenile DTC. METHODS: Fifty-one DTC patients (32 girls
      and 19 boys; <= 20 y old; mean age, 16.5 y) were treated with (131)I
      (radioiodine, or radioactive iodine [RAI]); the median follow-up was 10 y.
      Patients underwent different initial treatments: 46 patients received total
      thyroidectomy and RAI, 3 patients received total thyroidectomy, and 3 patients
      received subtotal thyroidectomy. The probability of recurrence and prognostic
      factors were tested with the Kaplan-Meier method. RESULTS: Initially, 36 of 51
      patients achieved complete remission, 14 of 51 achieved partial remission, and 1
      of 51 had progressive disease. By the follow-up, 11 of 51 patients (21.6%) had
      developed recurrent disease; the median appearance time was 4 y (range, 1-15 y).
      The probabilities of recurrence were 16.7% at 5 y, 22.3% at 10 y, and 33.3% at 15
      and 23 y after the initial treatments. Factors that were strongly predictive of
      recurrence were age (P = 0.001), initial treatment (P = 0.0001), and tumor
      multifocality (P = 0.011). Sex, nodal metastases at presentation, distal
      metastases at presentation, histologic type of the tumor, T stage, and clinical
      stage had no influence on relapse (P = 0.180, P = 0.786, P = 0.796, P = 0.944, P
      = 0.352, and P = 0.729, respectively). Patients with recurrent disease, partial
      remission, and progressive disease were retreated, with either surgery or surgery
      and RAI, receiving cumulative activities of up to 40 GBq. The overall outcome in
      our patients was excellent: 90.2% complete remission, 3.92% partial remission,
      1.96% stable disease, 1.96% disease-related death, and 1.96% another cause of
      death. CONCLUSION: Younger age at diagnosis, less radical primary surgery without
      subsequent RAI, and tumor multifocality are factors that are strongly prognostic
      for recurrence. For reducing the rate of relapse and improving surveillance for
      recurrent disease, total thyroidectomy followed by RAI appears to be the most
      beneficial initial treatment for patients with juvenile DTC. The use of RAI seems
      to be safe, with no adverse effects on subsequent fertility and pregnancy or
      secondary malignancy.

PMID- 24722528
TI  - Thyroid cancer in children.

PMID- 24722525
TI  - Microglial dynamics and role in the healthy and diseased brain: a paradigm of
      functional plasticity.
AB  - The study of the dynamics and functions of microglia in the healthy and diseased
      brain is a matter of intense scientific activity. The application of new
      techniques and new experimental approaches has allowed the identification of
      novel microglial functions and the redefinition of classic ones. In this review,
      we propose the study of microglial functions, rather than their molecular
      profiles, to better understand and define the roles of these cells in the brain.
      We review current knowledge on the role of surveillant microglia, proliferating
      microglia, pruning/neuromodulatory microglia, phagocytic microglia, and
      inflammatory microglia and the molecular profiles that are associated with these
      functions. In the remodeling scenario of microglial biology, the analysis of
      microglial functional states will inform about the roles in health and disease
      and will guide us to a more precise understanding of the multifaceted roles of
      this never-resting cells. 

PMID- 24722523
TI  - Molecular pathways and therapeutic targets in lung cancer.
AB  - Lung cancer is still the leading cause of cancer death worldwide. Both
      histologically and molecularly lung cancer is heterogeneous. This review
      summarizes the current knowledge of the pathways involved in the various types of
      lung cancer with an emphasis on the clinical implications of the increasing
      number of actionable molecular targets. It describes the major pathways and
      molecular alterations implicated in the development and progression of non-small
      cell lung cancer (adenocarcinoma and squamous cancer), and of small cell
      carcinoma, emphasizing the molecular alterations comprising the specific
      blueprints in each group. The approved and investigational targeted therapies as
      well as the immune therapies, and clinical trials exploring the variety of
      targeted approaches to treatment of lung cancer are the main focus of this
      review. 

PMID- 24722529
TI  - Implementation of Multi-Curie Production of (99m)Tc by Conventional Medical
      Cyclotrons.
AB  - (99m)Tc is currently produced by an aging fleet of nuclear reactors, which
      require enriched uranium and generate nuclear waste. We report the development of
      a comprehensive solution to produce (99m)Tc in sufficient quantities to supply a
      large urban area using a single medical cyclotron. METHODS: A new target system
      was designed for (99m)Tc production. Target plates made of tantalum were coated
      with a layer of (100)Mo by electrophoretic deposition followed by high
      temperature sintering. The targets were irradiated with 18-MeV protons for up to
      6 h, using a medical cyclotron. The targets were automatically retrieved and
      dissolved in 30% H2O2. (99m)Tc was purified by solid-phase extraction or biphasic
      exchange chromatography. RESULTS: Between 1.04 and 1.5 g of (100)Mo were
      deposited on the tantalum plates. After high-temperature sintering, the (100)Mo
      formed a hard, adherent layer that bonded well with the backing surface. The
      targets were irradiated for 1-6.9 h at 20-240 MUA of proton beam current,
      producing up to 348 GBq (9.4 Ci) of (99m)Tc. The resulting pertechnetate passed
      all standard quality control procedures and could be used to reconstitute typical
      anionic, cationic, and neutral technetium radiopharmaceutical kits. CONCLUSION:
      The direct production of (99m)Tc via proton bombardment of (100)Mo can be
      practically achieved in high yields using conventional medical cyclotrons. With
      some modifications of existing cyclotron infrastructure, this approach can be
      used to implement a decentralized medical isotope production model. This method
      eliminates the need for enriched uranium and the radioactive waste associated
      with the processing of uranium targets.

PMID- 24722530
TI  - Adjuvant Intraarterial Lipiodol or 131I-Lipiodol After Curative Treatment of
      Hepatocellular Carcinoma: A Prospective Randomized Trial.
AB  - The prevention of tumor recurrence after curative treatment of hepatocellular
      carcinoma (HCC) is unresolved. Postoperative intraarterial injection of (131)I
      labeled lipiodol has been proposed as adjuvant treatment. The aim of this
      prospective randomized trial was to evaluate if a single dose of postoperative
      adjuvant intraarterial (131)I-lipiodol (vs. unlabeled lipiodol) could reduce the
      rate of intrahepatic recurrence at 2 y. METHODS: Patients who underwent curative
      treatment for HCC and recovered within 6 wk were randomly assigned to receive a
      single 2,200-MBq (131)I-lipiodol dose or a single unlabeled lipiodol dose on a
      1:1 basis. Recurrence-free and overall survival rates were analyzed. RESULTS:
      Between June 2005 and February 2009, we included 58 patients (median age of 63 y
      [range, 23-85 y]): 29 received intraarterial (131)I-lipiodol and 29 received
      lipiodol adjuvant treatment. At 2 y after treatment, the rate of patients with
      intrahepatic recurrence was 28% in the (131)I-lipiodol group and 56% in the
      lipiodol group (P = 0.0449). The Kaplan-Meier analysis confirmed this result,
      with a 2-y recurrence-free survival in the (131)I-lipiodol and lipiodol groups of
      73% and 45%, respectively (P = 0.0259). The 5-y recurrence-free survival rates in
      the (131)I-lipiodol and lipiodol groups were 40% and 0%, respectively (P =
      0.0184). The overall and specific survivals were not significantly different
      between groups (P = 0.9378 and P = 0.1339, respectively). (131)I-lipiodol had no
      severe toxic effects. CONCLUSION: After curative treatment of patients with HCC,
      one 2,200-MBq dose of intraarterial (131)I-lipiodol significantly decreased the
      rate of intrahepatic recurrence but failed to improve overall or specific
      survival.

PMID- 24722531
TI  - Differences in metabolic network modulation between capsulotomy and deep-brain
      stimulation for refractory obsessive-compulsive disorder.
AB  - Around 7%-10% of patients with obsessive-compulsive disorder (OCD) are refractory
      to first-line treatment. Neurosurgical approaches are available such as
      capsulotomy or deep-brain stimulation (DBS). There is strong evidence for central
      involvement of the corticostriatopallidothalamocortical (CSPTC) circuit in OCD,
      but the exact mechanism through which these interventions lead to clinical
      improvement and potential differences in network modulation are not fully
      understood. METHODS: In total, 13 capsulotomy patients (aged 29-59 y, 10 men and
      3 women) and 16 DBS patients (aged 25-56 y, 6 men and 10 women) were
      prospectively included. (18)F-FDG PET was performed before and after capsulotomy
      and before and after DBS in both stimulation-on and stimulation-off conditions.
      Presurgical scans were compared with scans of healthy volunteers using SPM8 and
      global scaling, and metabolic changes after DBS were compared with changes after
      capsulotomy. Correlations with clinical improvements were investigated using the
      Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) and the Hamilton Depression Rating
      Scale (HAM-D). RESULTS: Both groups had similar pretreatment clinical morbidity
      as assessed by Y-BOCS and the Hamilton Depression Rating Scale. Preoperative
      superior frontal and supplementary motor cortex hypometabolism was common to both
      patient groups, and the subgenual anterior cingulate, occipital cortex (cuneus),
      and posterior cerebellum were relatively hypermetabolic. Postoperative metabolic
      decreases were common to both interventions in the anterior cingulate and the
      prefrontal and orbitofrontal cortices. Compared with DBS, capsulotomy resulted in
      more intense metabolic changes, with additional significant decreases in the
      mediodorsal thalamus, caudate nucleus, and cerebellum as well as increases in the
      precuneus and the fusiform and lingual gyrus. The stimulation-off condition of
      DBS patients showed no significant differences from the preoperative state.
      Improvement in Y-BOCS scores correlated with metabolic changes in the occipital
      cortex. Baseline metabolism in the subgenual anterior cingulate and superior
      temporal cortices were related to postoperative improvement of depressive
      symptoms. CONCLUSION: Capsulotomy and DBS lead to similar clinical improvement
      and similar metabolic network changes in the CSPTC circuit, with a prominent role
      for the subgenual anterior cingulate and other core structures of the CSPTC.
      However, metabolic changes are more pronounced and extended in capsulotomy than
      in DBS. Furthermore, cortical regions outside the CSPTC may also play an
      important role in OCD symptomatology.

PMID- 24722532
TI  - Fusion of protegrin-1 and plectasin to MAP30 shows significant inhibition
      activity against dengue virus replication.
AB  - Dengue virus (DENV) broadly disseminates in tropical and sub-tropical countries
      and there are no vaccine or anti-dengue drugs available. DENV outbreaks cause
      serious economic burden due to infection complications that requires special
      medical care and hospitalization. This study presents a new strategy for
      inexpensive production of anti-DENV peptide-fusion protein to prevent and/or
      treat DENV infection. Antiviral cationic peptides protegrin-1 (PG1) and plectasin
      (PLSN) were fused with MAP30 protein to produce recombinant antiviral peptide
      fusion protein (PG1-MAP30-PLSN) as inclusion bodies in E. coli. High yield
      production of PG1-MAP30-PLSN protein was achieved by solubilization of inclusion
      bodies in alkaline buffer followed by the application of appropriate refolding
      techniques. Antiviral PG1-MAP30-PLSN protein considerably inhibited DENV protease
      (NS2B-NS3pro) with half-maximal inhibitory concentration (IC50) 0.5+/-0.1 MUM.
      The real-time proliferation assay (RTCA) and the end-point proliferation assay
      (MTT assay) showed that the maximal-nontoxic dose of the peptide-fusion protein
      against Vero cells is approximately 0.67+/-0.2 MUM. The cell-based assays showed
      considerable inhibition of the peptide-fusion protein against binding and
      proliferating stages of DENV2 into the target cells. The peptide-fusion protein
      protected DENV2-challeged mice with 100% of survival at the dose of 50 mg/kg. In
      conclusion, producing recombinant antiviral peptide-fusion protein by combining
      short antiviral peptide with a central protein owning similar activity could be
      useful to minimize the overall cost of short peptide production and take
      advantage of its synergistic antiviral activities. 

PMID- 24722533
TI  - Electric-field-induced local structural phenomena in relaxor ferroelectric
      PbSc(0.5)Nb(0.5)O3 near the intermediate temperature T* studied by Raman
      spectroscopy.
AB  - Raman spectroscopy at different temperatures and under an external electric field
      E was applied to PbSc0.5Nb0.5O3 single crystals in order to gain further insights
      into the mesoscopic-scale coupling processes in perovskite-type (ABO3) relaxor
      ferroelectrics. Parallel and cross-polarized Raman spectra were collected between
      800-80 K with E applied along the cubic [1 0 0], [1 1 0] or [1 1 1]
      crystallographic directions. The analysis was focused on the field-induced
      changes in the temperature evolution of three low-energy phonon modes: the Pb
      localized mode near 50 cm(-1), the Pb-BO3 translation mode near 150 cm(-1), and
      the B-cation-localized mode near 250 cm(-1). The results show that competitive
      ferroelectric (FE) and antiferroelectric (AFE) coupling exists within the system
      of off-centred Pb(2+) cations, within the system of off-centred B-site cations as
      well as between off-centred Pb(2+) and B-site cations. The strong AFE-type
      coupling between Pb(2+) cations along the cubic body diagonal significantly
      influences the coupling between the B-site cations via the Pb-BO3 mode and
      results in AFE-type behaviour of the 'microscopic' T* determined from the B
      cation-localized mode near 250 cm(-1), which explains the previously reported non
      trivial field dependence of the 'macroscopic' characteristic temperatures: the
      temperature of the dielectric-permittivity maximum Tm, T*, and the Burns
      temperature TB. The comparative analysis between PbSc0.5Nb0.5O3 and
      PbSc0.5Ta0.5O3 indicates that two major displacive order parameters couple to
      form a relaxor state in B-site complex perovskites: the FE order associated with
      polar shifts of B-site cations and the AFE order associated with polar shifts of
      A-site cations. The latter penetrates through both polar and non-polar regions,
      but it is highly frustrated due to the high density of translation-symmetry
      faults in the chemical NaCl-type B-site order. The frustrated AFE order of off
      centred A-site cations might be the key factor for the existence of a relaxor
      state. 

PMID- 24722534
TI  - Hepatitis C virus infection among injection drug users with and without human
      immunodeficiency virus co-infection.
AB  - The aim of this study is to explore the prevalence of hepatitis C virus (HCV)
      infection among injection drug users (IDUs) with and without human
      immunodeficiency virus (HIV) infection in southern Taiwan. For 562 IDUs (265 anti
      HIV negative, 297 anti-HIV positive), we analyzed liver function, anti-HIV
      antibody, anti-HCV antibody, HCV viral loads, and hepatitis B surface antigen
      (HBsAg). HIV RNA viral loads and CD4 cell count for anti-HIV-seropositive IDUs
      and the HCV genotype for HCV RNA-seropositive IDUs were measured. The
      seroprevalence rates of anti-HIV, anti-HCV, and HBsAg were 52.8%, 91.3%, and
      15.3%, respectively. All the anti-HIV-seropositive IDUs were positive for HIV
      RNA. Anti-HCV seropositivity was the most important factor associated with HIV
      infection (odds ratio [OR], 25.06; 95% confidence intervals [CI], 8.97-74.9),
      followed by male gender (OR, 6.12; 95% CI, 4.05-9.39) and HBsAg seropositivity
      (OR, 1.90; 95% CI, 1.11-3.34). Among IDUs positive for anti-HCV, 80.7% had
      detectable HCV RNA. HCV viremia after HCV exposure was strongly related to HIV
      infection (OR, 6.262; 95% CI, 1.515-18.28), but negatively correlated to HBsAg
      seropositivity (OR, 0.161; 95% CI, 0.082-0.317). HCV genotype 6 was the most
      prevalent genotype among all IDUs (41.0%), followed by genotypes 1 (32.3%), 3
      (12.8%), and 2 (5.6%). In conclusion, about half IDUs were infected with HIV and
      >90% with HCV infection. Male and seropositivity for HBsAg and anti-HCV were
      factors related to HIV infection among our IDUs. HIV was positively correlated,
      whereas hepatitis B co-infection was negatively correlated with HCV viremia among
      IDUs with HCV exposure. Different HCV molecular epidemiology was noted among
      IDUs.

PMID- 24722535
TI  - Molecular modeling and imaging of initial stages of cellulose fibril assembly:
      evidence for a disordered intermediate stage.
AB  - The remarkable mechanical strength of cellulose reflects the arrangement of
      multiple beta-1,4-linked glucan chains in a para-crystalline fibril. During plant
      cellulose biosynthesis, a multimeric cellulose synthesis complex (CSC) moves
      within the plane of the plasma membrane as many glucan chains are synthesized
      from the same end and in close proximity. Many questions remain about the
      mechanism of cellulose fibril assembly, for example must multiple catalytic
      subunits within one CSC polymerize cellulose at the same rate? How does the
      cellulose fibril bend to align horizontally with the cell wall? Here we used
      mathematical modeling to investigate the interactions between glucan chains
      immediately after extrusion on the plasma membrane surface. Molecular dynamics
      simulations on groups of six glucans, each originating from a position
      approximating its extrusion site, revealed initial formation of an uncrystallized
      aggregate of chains from which a protofibril arose spontaneously through a
      ratchet mechanism involving hydrogen bonds and van der Waals interactions between
      glucose monomers. Consistent with the predictions from the model, freeze-fracture
      transmission electron microscopy using improved methods revealed a hemispherical
      accumulation of material at points of origination of apparent cellulose fibrils
      on the external surface of the plasma membrane where rosette-type CSCs were also
      observed. Together the data support the possibility that a zone of uncrystallized
      chains on the plasma membrane surface buffers the predicted variable rates of
      cellulose polymerization from multiple catalytic subunits within the CSC and acts
      as a flexible hinge allowing the horizontal alignment of the crystalline
      cellulose fibrils relative to the cell wall. 

PMID- 24722536
TI  - Relationship of renin-angiotensin-aldosterone system polymorphisms and phenotypes
      to mortality in Chinese coronary atherosclerosis patients.
AB  - We performed a large, long-term cohort study to evaluate the association of renin
      angiotensin-aldosterone system gene polymorphisms and baseline phenotypes to all
      cause mortality among patients with angiographically confirmed coronary
      atherosclerosis. The study included 1075 subjects who underwent coronary
      angiography. Patients were genotyped for eight polymorphisms (rs4343, rs5186,
      rs5182, rs5049, rs5051, rs699, rs4762, and rs1799998), and their baseline plasma
      angiotensin II and aldosterone levels were measured. The interval between
      baseline and follow-up time-points ranged from 6.39 to 9.59 years. The results of
      multivariate regression analysis further indicated that high baseline angiotensin
      II levels (1.226 (1.024-1.468), p = 0.027) were independently associated with all
      cause death. Therefore, we found that an increased baseline plasma angiotensin II
      level was associated with higher long-term all-cause mortality, even after
      correcting for established cardiovascular risk factors. 

PMID- 24722537
TI  - Patient- and clinic visit-related factors associated with potentially
      inappropriate medication use among older home healthcare service recipients.
AB  - OBJECTIVES: Taiwanese National Health Insurance (TNHI) provides home healthcare
      services to patients with skilled nursing needs who were homebound or lived in
      nursing homes. Studies on potentially inappropriate medications (PIMs) for older
      home healthcare service recipients (HHSRs) are growing, but comparisons among
      newer criteria of PIMs have not been applied. The aim of this study was to
      explore the prevalence and correlates of PIMs based on three different
      instruments published after 2010 among older HHSRs. MATERIALS AND METHODS: We
      performed cross-sectional analysis of the TNHI Research Database. A total of
      25,187 HHSRs aged more than 65 years in 2009 were included. Medication lists
      independent of chronic conditions from the 2012 Beers criteria, PIM-Taiwan
      criteria, and the PRISCUS (Latin for "old and venerable") criteria were used.
      Analysis was performed separately at patient and clinic-visit level. T-tests, chi
      square analysis, and multivariate logistic regressions were used where
      appropriate. RESULTS: The prevalence of having at least one PIM at patient and
      clinic-visit level was highest with the Beers (82.67%, 36.14% respectively),
      followed by the PRISCUS (68.49%, 25.13%) and PIM-Taiwan (63.04%, 19.21%)
      criteria. At patient level, polypharmacy (odds ratio (OR) 2.53 to 4.90), higher
      number of clinic (OR 1.15 to 1.41), hospital (OR 1.24 to 1.64), and physician (OR
      1.15 to 1.41) visits were associated with PIM use for all 3 sets of criteria. At
      clinic-visit level, internist/family physicians (OR 1.26 to 1.72) and
      neurologists/psychiatrists (OR 1.73 to 5.87) were more likely to prescribe PIMs
      than others. Psychotropic drugs and first generation antihistamines accounted for
      most of the top ten PIMs. CONCLUSION: The prevalence of PIMs was high among older
      Taiwanese HHSRs. Polypharmacy and certain medical specialties were associated
      with a higher likelihood of PIM prescriptions. Provider education and medication
      review and reconciliation should be considered.

PMID- 24722538
TI  - Meta-analysis of prospective cohort studies of cigarette smoking and the
      incidence of colon and rectal cancers.
AB  - Although the American College of Gastroenterology colorectal cancer screening
      guidelines highlight cigarette smoking as a risk factor, cigarette smoking is
      still an arguably underappreciated risk factor for this disease, especially for
      its subsites: colon cancer (CC) and rectal cancer (RC). A literature search of
      MEDLINE and EMBASE was performed up to 30 April 2013 for prospective cohort
      studies. A random-effects meta-analysis was carried out to estimate the summary
      relative risks (SRRs) and 95% confidence intervals (CIs) for the associations. A
      total of 24 prospective studies, which reported data for cigarette smoking and
      incidence of CC and RC separately, were included. Our analysis showed that,
      compared with never-smokers, current smokers had a higher risk of RC than CC (CC:
      SRR=1.09, 95% CI, 1.01-1.18; RC: SRR=1.24, 95% CI, 1.16-1.39; PRC vs. CC=0.034),
      whereas former smokers had a similar risk of CC and RC. Current smokers had a
      significantly higher risk of proximal CC than distal CC (P=0.035). This meta
      analysis suggests that cigarette smoking is associated with an increased risk of
      both CC and RC, and that the magnitude of the association is stronger for RC than
      that for CC. 

PMID- 24722539
TI  - Dietary extra-virgin olive oil and corn oil differentially modulate the mRNA
      expression of xenobiotic-metabolizing enzymes in the liver and in the mammary
      gland in a rat chemically induced breast cancer model.
AB  - High extra-virgin olive oil (EVOO) and corn oil diets differentially modulate
      experimental mammary carcinogenesis. We have investigated their influence on the
      initiation stage through the modulation of the expression of xenobiotic
      metabolizing enzymes (XMEs) in the liver and the mammary gland. Female Sprague
      Dawley rats were fed a low-fat (LF), high corn oil (HCO), or high EVOO (HOO) diet
      from weaning and gavaged with 7,12-dimethylbenz(a)anthracene (DMBA). The HCO diet
      increased the mRNA levels of the phase I enzymes CYP1A1, CYP1A2 and, to a lesser
      extent, CYP1B1, in the liver. The Aryl hydrocarbon receptor (AhR) seemed to be
      involved in this upregulated CYP1 expression. However, a slight trend toward an
      increase in the mRNA levels of the phase II enzymes GSTP1 and NQO1 was observed
      with the HOO diet. At least in the case of GSTP1, this effect was linked to an
      increased Nrf2 transactivation activity. This different regulation of the XMEs
      expression led, in the case of the HCO diet, to a balance between the production
      of active carcinogenic compounds and their inactivation tilted toward phase I,
      which would stimulate DMBA-induced cancer initiation, whereas the HOO diet was
      associated with a slower phase I metabolism accompanied by a faster phase II
      detoxification, thus reducing the output of the active compounds to the target
      tissues. In the mammary gland, the differential effects of diets may be
      conditioned by the state of cell differentiation, sexual maturity, and hormone
      metabolism. 

PMID- 24722540
TI  - The immune strategy and stress response of the Mediterranean species of the
      Bemisia tabaci complex to an orally delivered bacterial pathogen.
AB  - BACKGROUND: The whitefly, Bemisia tabaci, a notorious agricultural pest, has
      complex relationships with diverse microbes. The interactions of the whitefly
      with entomopathogens as well as its endosymbionts have received great attention,
      because of their potential importance in developing novel whitefly control
      technologies. To this end, a comprehensive understanding on the whitefly defense
      system is needed to further decipher those interactions. METHODOLOGY/PRINCIPAL
      FINDINGS: We conducted a comprehensive investigation of the whitefly's defense
      responses to infection, via oral ingestion, of the pathogen, Pseudomonas
      aeruginosa, using RNA-seq technology. Compared to uninfected whiteflies, 6 and 24
      hours post-infected whiteflies showed 1,348 and 1,888 differentially expressed
      genes, respectively. Functional analysis of the differentially expressed genes
      revealed that the mitogen associated protein kinase (MAPK) pathway was activated
      after P. aeruginosa infection. Three knottin-like antimicrobial peptide genes and
      several components of the humoral and cellular immune responses were also
      activated, indicating that key immune elements recognized in other insect species
      are also important for the response of B. tabaci to pathogens. Our data also
      suggest that intestinal stem cell mediated epithelium renewal might be an
      important component of the whitefly's defense against oral bacterial infection.
      In addition, we show stress responses to be an essential component of the defense
      system. CONCLUSIONS/SIGNIFICANCE: We identified for the first time the key immune
      response elements utilized by B. tabaci against bacterial infection. This study
      provides a framework for future research into the complex interactions between
      whiteflies and microbes.

PMID- 24722541
TI  - TP53 supports basal-like differentiation of mammary epithelial cells by
      preventing translocation of deltaNp63 into nucleoli.
AB  - Multiple observations suggest a cell type-specific role for TP53 in mammary
      epithelia. We developed an in vitro assay, in which primary mouse mammary
      epithelial cells (mMECs) progressed from lumenal to basal-like phenotypes based
      on expression of Krt18 or DeltaNp63, respectively. Such transition was markedly
      delayed in Trp53(-/-) mMECs suggesting that Trp53 is required for specification
      of the basal, but not lumenal cells. Evidence from human basal-like cell lines
      suggests that TP53 may support the activity of DeltaNp63 by preventing its
      translocation from nucleoplasm into nucleoli. In human lumenal cells, activation
      of TP53 by inhibiting MDM2 or BRCA1 restored the nucleoplasmic expression of
      DeltaNp63. Trp53(-/-) mMECs eventually lost epithelial features resulting in
      upregulation of MDM2 and translocation of DeltaNp63 into nucleoli. We propose
      that TP63 may contribute to TP53-mediated oncogenic transformation of epithelial
      cells and shed light on tissue- and cell type-specific biases observed for TP53
      related cancers. 

PMID- 24722542
TI  - European monitoring systems and data for assessing environmental and climate
      impacts on human infectious diseases.
AB  - Surveillance is critical to understanding the epidemiology and control of
      infectious diseases. The growing concern over climate and other drivers that may
      increase infectious disease threats to future generations has stimulated a review
      of the surveillance systems and environmental data sources that might be used to
      assess future health impacts from climate change in Europe. We present an
      overview of organizations, agencies and institutions that are responsible for
      infectious disease surveillance in Europe. We describe the surveillance systems,
      tracking tools, communication channels, information exchange and outputs in light
      of environmental and climatic drivers of infectious diseases. We discuss
      environmental and climatic data sets that lend themselves to epidemiological
      analysis. Many of the environmental data sets have a relatively uniform quality
      across EU Member States because they are based on satellite measurements or EU
      funded FP6 or FP7 projects with full EU coverage. Case-reporting systems for
      surveillance of infectious diseases should include clear and consistent case
      definitions and reporting formats that are geo-located at an appropriate
      resolution. This will allow linkage to environmental, social and climatic sources
      that will enable risk assessments, future threat evaluations, outbreak management
      and interventions to reduce disease burden. 

PMID- 24722543
TI  - Spatial analysis of HIV positive injection drug users in San Francisco, 1987 to
      2005.
AB  - Spatial analyses of HIV/AIDS related outcomes are growing in popularity as a tool
      to understand geographic changes in the epidemic and inform the effectiveness of
      community-based prevention and treatment programs. The Urban Health Study was a
      serial, cross-sectional epidemiological study of injection drug users (IDUs) in
      San Francisco between 1987 and 2005 (N = 29,914). HIV testing was conducted for
      every participant. Participant residence was geocoded to the level of the United
      States Census tract for every observation in dataset. Local indicator of spatial
      autocorrelation (LISA) tests were used to identify univariate and bivariate
      Census tract clusters of HIV positive IDUs in two time periods. We further
      compared three tract level characteristics (% poverty, % African Americans, and %
      unemployment) across areas of clustered and non-clustered tracts. We identified
      significant spatial clustering of high numbers of HIV positive IDUs in the early
      period (1987-1995) and late period (1996-2005). We found significant bivariate
      clusters of Census tracts where HIV positive IDUs and tract level poverty were
      above average compared to the surrounding areas. Our data suggest that poverty,
      rather than race, was an important neighborhood characteristic associated with
      the spatial distribution of HIV in SF and its spatial diffusion over time. 

PMID- 24722544
TI  - Body size perception and weight control in youth: 9-year international trends
      from 24 countries.
AB  - OBJECTIVES: To examine 9-year trends and relationships regarding misperceptions
      of body size and dieting for weight loss among adolescents from 24 countries, and
      explore the influence of country-level overweight prevalence. METHODS:
      Sociodemographic characteristics, body size perception and dieting for weight
      loss were assessed in the Health Behaviour in School-aged Children survey
      conducted in 24 countries cross-sectionally at three time points (2001/2002,
      2005/2006 and 2009/2010). Logistic regression models examined change over time in
      overestimation of body size in non-overweight adolescents, underestimation of
      body size in overweight adolescents, dieting for weight loss in non-overweight
      and overweight adolescents and relationships between body size perception and
      dieting. Analyses were stratified by weight status and sex. Covariates included
      country-level overweight prevalence, family affluence and country level of
      development. Body mass index was only included in models examining dieting for
      weight loss. RESULTS: Country-level overweight prevalence increased over time
      (11.6-14.7%). Compared with Time 1, overweight adolescents had greater odds of
      body size underestimation at Time 3 (odds ratio (OR)=1.68 for girls; OR=1.10 for
      boys), whereas non-overweight adolescents had lower odds of body size
      overestimation at Time 3 (OR=0.87 for girls; OR=0.89 for boys). Controlling for
      country-level overweight prevalence attenuated these relationships. Compared with
      Time 1, overweight and non-overweight boys were 10% more likely to diet at Time
      3, whereas overweight and non-overweight girls were 19% and 16%, respectively,
      less likely to diet at Time 3. Controlling for country-level overweight
      prevalence did not impact trends in dieting for weight loss. Additionally, the
      association of self-perceived overweight with increased odds of dieting
      diminished over time. CONCLUSIONS: Body size perceptions among adolescents may
      have changed over time concurrent with shifts in country-level body weight.
      However, controlling for country-level overweight prevalence did not impact
      trends in dieting for weight loss, suggesting a potentially stronger impact of
      social comparison on weight-related perceptions than on behavior.

PMID- 24722545
TI  - Associations between infant feeding and the size, tempo and velocity of infant
      weight gain: SITAR analysis of the Gemini twin birth cohort.
AB  - OBJECTIVE: Infant growth trajectories, in terms of size, tempo and velocity, may
      programme lifelong obesity risk. Timing of breastfeeding cessation and weaning
      are both implicated in rapid infant growth; we examined the association of both
      simultaneously with a range of growth parameters. DESIGN: Longitudinal population
      based twin birth cohort. SUBJECTS: The Gemini cohort provided data on 4680 UK
      infants with a median of 10 (interquartile range=8-15) weight measurements
      between birth and a median of 6.5 months. Age at breastfeeding cessation and
      weaning were reported by parents at mean age 8.2 months (s.d.=2.2, range=4-20).
      Growth trajectories were modelled using SuperImposition by Translation And
      Rotation (SITAR) to generate three descriptors of individual growth relative to
      the average trajectory: size (grams), tempo (weeks, indicating the timing of the
      peak growth rate) and velocity (% difference from average, reflecting mean growth
      rate). Complex-samples general linear models adjusting for family clustering and
      confounders examined associations between infant feeding and SITAR parameters.
      RESULTS: Longer breastfeeding (>4 months vs never) was independently associated
      with lower growth velocity by 6.8% (s.e.=1.3%) and delayed growth tempo by 1.0
      (s.e.=0.2 weeks), but not with smaller size. Later weaning (?6 months vs <4
      months) was independently associated with lower growth velocity by 4.9%
      (s.e.=1.1%) and smaller size by 102 g (s.e.=25 g). CONCLUSIONS: Infants breastfed
      for longer grew slower for longer after birth (later peak growth rate) but were
      no different in size, while infants weaned later grew slower overall and were
      smaller but the timing of peak growth did not differ. Slower trajectories with a
      delayed peak in growth may have beneficial implications for programming later
      obesity risk. Replication in cohorts with longer follow-up, alternative
      confounding structures or randomised controlled trials are required to confirm
      the long-term effects and directionality, and to rule out residual confounding.

PMID- 24722546
TI  - Urinary concentrations of bisphenol A and phthalate metabolites and weight
      change: a prospective investigation in US women.
AB  - OBJECTIVE: Both bisphenol A (BPA) and phthalates are known endocrine-disrupting
      chemicals for which there is widespread general population exposure. Human
      exposure occurs through dietary and non-dietary routes. Although animal studies
      have suggested a potential role of these chemicals in obesity, evidence from
      human studies is sparse and inconsistent, and prospective evidence is lacking.
      This study evaluated urinary concentrations of BPA and major phthalate
      metabolites in relation to prospective weight change. METHODS: The study
      population was from the controls in a prospective case-control study of type 2
      diabetes in the Nurses' Health Study (NHS) and NHSII. A total of 977 participants
      provided first-morning-void urine samples in 1996-2002. Urinary concentrations of
      BPA and nine phthalate metabolites were measured using liquid chromatography-mass
      spectrometry. Body weights were self-reported at baseline and updated biennially
      thereafter for 10 years. RESULTS: On average, the women gained 2.09 kg (95%
      confidence interval (CI), -2.27 to 6.80 kg) during the 10-year follow-up. In
      multivariate analysis with adjustment of lifestyle and dietary factors, in
      comparison with women in the lowest quartile of BPA concentration, those in the
      highest quartile had 0.23 kg per year (95% CI, 0.07-0.38 kg per year) greater
      weight gain during the 10-year follow-up (P-trend=0.02). Several phthalate
      metabolites, including phthalic acid, MBzP and monobutyl phthalate, were also
      associated with faster prospective weight gain in a dose-response fashion (P
      trend<0.01), whereas other phthalates metabolites, including MEP and
      monoethylhexyl phthalate, were not monotonically associated with body weight
      change. CONCLUSIONS: These data suggest urinary concentrations of BPA and certain
      individual phthalate metabolites that were associated with modestly greater
      weight gain in a dose-response fashion. These data are consistent with a
      potential role of BPA and phthalates in obesity, although more prospective data
      are needed to corroborate these observations.

PMID- 24722547
TI  - The interaction of CRM1 and the nuclear pore protein Tpr.
AB  - While much has been devoted to the study of transport mechanisms through the
      nuclear pore complex (NPC), the specifics of interactions and binding between
      export transport receptors and the NPC periphery have remained elusive. Recent
      work has demonstrated a binding interaction between the exportin CRM1 and the
      unstructured carboxylic tail of Tpr, on the nuclear basket. Strong evidence
      suggests that this interaction is vital to the functions of CRM1. Using molecular
      dynamics simulations and a newly refined method for determining binding regions,
      we have identified nine candidate binding sites on CRM1 for C-Tpr. These include
      two adjacent to RanGTP--from which one is blocked in the absence of RanGTP--and
      three next to the binding region of the cargo Snurportin. We report two
      additional interaction sites between C-Tpr and Snurportin, suggesting a possible
      role for Tpr import into the nucleus. Using bioinformatics tools we have
      conducted conservation analysis and functional residue prediction investigations
      to identify which parts of the obtained binding sites are inherently more
      important and should be highlighted. Also, a novel measure based on the ratio of
      available solvent accessible surface (RASAS) is proposed for monitoring the
      ligand/receptor binding process.

PMID- 24722548
TI  - Cryptosporidium,Giardia, Cryptococcus, Pneumocystis genetic variability: cryptic
      biological species or clonal near-clades?
AB  - An abundant literature dealing with the population genetics and taxonomy of
      Giardia duodenalis, Cryptosporidium spp., Pneumocystis spp., and Cryptococcus
      spp., pathogens of high medical and veterinary relevance, has been produced in
      recent years. We have analyzed these data in the light of new population genetic
      concepts dealing with predominant clonal evolution (PCE) recently proposed by us.
      In spite of the considerable phylogenetic diversity that exists among these
      pathogens, we have found striking similarities among them. The two main PCE
      features described by us, namely highly significant linkage disequilibrium and
      near-clading (stable phylogenetic clustering clouded by occasional
      recombination), are clearly observed in Cryptococcus and Giardia, and more
      limited indication of them is also present in Cryptosporidium and Pneumocystis.
      Moreover, in several cases, these features still obtain when the near-clades that
      subdivide the species are analyzed separately ("Russian doll pattern"). Lastly,
      several sets of data undermine the notion that certain microbes form clonal
      lineages simply owing to a lack of opportunity to outcross due to low
      transmission rates leading to lack of multiclonal infections ("starving sex
      hypothesis"). We propose that the divergent taxonomic and population genetic
      inferences advanced by various authors about these pathogens may not correspond
      to true evolutionary differences and could be, rather, the reflection of
      idiosyncratic practices among compartmentalized scientific communities. The PCE
      model provides an opportunity to revise the taxonomy and applied research dealing
      with these pathogens and others, such as viruses, bacteria, parasitic protozoa,
      and fungi. 

PMID- 24722549
TI  - TRANSPARENT TESTA8 Inhibits Seed Fatty Acid Accumulation by Targeting Several
      Seed Development Regulators in Arabidopsis.
AB  - Fatty acids (FAs) and FA-derived complex lipids play important roles in plant
      growth and vegetative development and are a class of prominent metabolites stored
      in mature seeds. The factors and regulatory networks that control FA accumulation
      in plant seeds remain largely unknown. The role of TRANSPARENT TESTA8 (TT8) in
      the regulation of flavonoid biosynthesis and the formation of seed coat color is
      extensively studied; however, its function in affecting seed FA biosynthesis is
      poorly understood. In this article, we show that Arabidopsis (Arabidopsis
      thaliana) TT8 acts maternally to affect seed FA biosynthesis and inhibits seed FA
      accumulation by down-regulating a group of genes either critical to embryonic
      development or important in the FA biosynthesis pathway. Moreover, the tt8
      mutation resulted in reduced deposition of protein in seeds during maturation.
      Posttranslational activation of a TT8-GLUCOCORTICOID RECEPTOR fusion protein and
      chromatin immunoprecipitation assays demonstrated that TT8 represses the
      activities of LEAFY COTYLEDON1, LEAFY COTYLEDON2, and FUSCA3, the critical
      transcriptional factors important for seed development, as well as
      CYTIDINEDIPHOSPHATE DIACYLGLYCEROL SYNTHASE2, which mediates glycerolipid
      biosynthesis. These results help us to understand the entire function of TT8 and
      increase our knowledge of the complicated networks regulating the formation of FA
      derived complex lipids in plant seeds.

PMID- 24722550
TI  - A Positive Regulator of Nodule Organogenesis, NODULE INCEPTION, Acts as a
      Negative Regulator of Rhizobial Infection in Lotus japonicus.
AB  - Legume-rhizobium symbiosis occurs in specialized root organs called nodules. To
      establish the symbiosis, two major genetically controlled events, rhizobial
      infection and organogenesis, must occur. For a successful symbiosis, it is
      essential that the two phenomena proceed simultaneously in different root
      tissues. Although several symbiotic genes have been identified during genetic
      screenings of nonsymbiotic mutants, most of the mutants harbor defects in both
      infection and organogenesis pathways, leading to experimental difficulty in
      investigating the molecular genetic relationships between the pathways. In this
      study, we isolated a novel nonnodulation mutant, daphne, in Lotus japonicus that
      shows complete loss of nodulation but a dramatically increased numbers of
      infection threads. Characterization of the locus responsible for these phenotypes
      revealed a chromosomal translocation upstream of NODULE INCEPTION (NIN) in
      daphne. Genetic analysis using a known nin mutant revealed that daphne is a novel
      nin mutant allele. Although the daphne mutant showed reduced induction of NIN
      after rhizobial infection, the spatial expression pattern of NIN in epidermal
      cells was broader than that in the wild type. Overexpression of NIN strongly
      suppressed hyperinfection in daphne, and daphne phenotypes were partially rescued
      by cortical expression of NIN. These observations suggested that the daphne
      mutation enhanced the role of NIN in the infection pathway due to a specific loss
      of the role of NIN in nodule organogenesis. Based on these results, we provide
      evidence that the bifunctional transcription factor NIN negatively regulates
      infection but positively regulates nodule organogenesis during the course of the
      symbiosis.

PMID- 24722552
TI  - A novel microfluidic system for the rapid analysis of protein thermal stability.
AB  - We describe a simple microfluidic device for the rapid analysis of protein
      thermal stability using a novel imaging method. The change in UV absorption upon
      thermal denaturation or aggregation of proteins is used to get a spatial image of
      proteins' folding or aggregation state along a linear temperature gradient. 

PMID- 24722551
TI  - Widespread use of non-productive alternative splice sites in Saccharomyces
      cerevisiae.
AB  - Saccharomyces cerevisiae has been used as a model system to investigate the
      mechanisms of pre-mRNA splicing but only a few examples of alternative splice
      site usage have been described in this organism. Using RNA-Seq analysis of
      nonsense-mediated mRNA decay (NMD) mutant strains, we show that many S.
      cerevisiae intron-containing genes exhibit usage of alternative splice sites, but
      many transcripts generated by splicing at these sites are non-functional because
      they introduce premature termination codons, leading to degradation by NMD.
      Analysis of splicing mutants combined with NMD inactivation revealed the role of
      specific splicing factors in governing the use of these alternative splice sites
      and identified novel functions for Prp17p in enhancing the use of branchpoint
      proximal upstream 3' splice sites and for Prp18p in suppressing the usage of a
      non-canonical AUG 3'-splice site in GCR1. The use of non-productive alternative
      splice sites can be increased in stress conditions in a promoter-dependent
      manner, contributing to the down-regulation of genes during stress. These results
      show that alternative splicing is frequent in S. cerevisiae but masked by RNA
      degradation and that the use of alternative splice sites in this organism is
      mostly aimed at controlling transcript levels rather than increasing proteome
      diversity. 

PMID- 24722553
TI  - Assessing the role of regulatory bodies in managing health professional issues
      and errors in Europe.
AB  - OBJECTIVE: This paper explores how medical regulatory bodies in nine European
      countries manage professional issues involving quality and patient safety, to
      build on limited existing information on procedures for regulating medical
      professionals in Europe. DESIGN: Twelve vignettes describing scenarios of
      concerns about standards of physicians were developed, covering clinical,
      criminal and administrative matters. Medical regulatory bodies in nine European
      countries were asked what action they would normally take in each situation.
      Their responses were related to their regulatory mandate. RESULTS: Responses
      varied greatly across participating countries. Regulators are always involved
      where patients are at risk or where a criminal offence is committed within the
      clinical setting. Non-criminal medical issues were generally handled by the
      employer, if any, at their discretion. Countries varied in the use of punitive
      measures, the extent to which they took an interest in issues arising outside
      professional activities, and whether they dealt with issues themselves or
      referred cases to another regulatory authority or took no action at all.
      CONCLUSIONS: There is little consistency across Europe on the regulation of
      medical professionals. There is considerable diversity in the range of topics
      that regulatory bodies oversee, with almost all covering health care quality and
      safety and others encompassing issues related to reputation, respect and trust.
      These inconsistencies have significant implications for professional mobility,
      patient safety and quality of care.

PMID- 24722555
TI  - Magnetic topological insulators at finite temperature.
AB  - In this paper, we study the two-dimensional magnetic topological insulators from
      the correlated Chern insulator and the correlated Z2 topological insulator at
      finite temperature. For the 2D correlated Chern insulator, we find that the
      thermal-fluctuation-induced magnetic topological insulator (MTI) appears in the
      intermediate interaction region of the correlated Chern insulator. On the
      contrary, for the correlated Z2 topological insulator, thermal-fluctuation
      induced MTI does not exist. Finally, we offer an explanation on the difference
      between the two cases. 

PMID- 24722554
TI  - Epidemiology of Coxiella burnetii infection in Africa: a OneHealth systematic
      review.
AB  - BACKGROUND: Q fever is a common cause of febrile illness and community-acquired
      pneumonia in resource-limited settings. Coxiella burnetii, the causative
      pathogen, is transmitted among varied host species, but the epidemiology of the
      organism in Africa is poorly understood. We conducted a systematic review of C.
      burnetii epidemiology in Africa from a "One Health" perspective to synthesize the
      published data and identify knowledge gaps. METHODS/PRINCIPAL FINDINGS: We
      searched nine databases to identify articles relevant to four key aspects of C.
      burnetii epidemiology in human and animal populations in Africa: infection
      prevalence; disease incidence; transmission risk factors; and infection control
      efforts. We identified 929 unique articles, 100 of which remained after full-text
      review. Of these, 41 articles describing 51 studies qualified for data
      extraction. Animal seroprevalence studies revealed infection by C. burnetii
      (<=13%) among cattle except for studies in Western and Middle Africa (18-55%).
      Small ruminant seroprevalence ranged from 11-33%. Human seroprevalence was <8%
      with the exception of studies among children and in Egypt (10-32%). Close contact
      with camels and rural residence were associated with increased seropositivity
      among humans. C. burnetii infection has been associated with livestock abortion.
      In human cohort studies, Q fever accounted for 2-9% of febrile illness
      hospitalizations and 1-3% of infective endocarditis cases. We found no studies of
      disease incidence estimates or disease control efforts. CONCLUSIONS/SIGNIFICANCE:
      C. burnetii infection is detected in humans and in a wide range of animal species
      across Africa, but seroprevalence varies widely by species and location. Risk
      factors underlying this variability are poorly understood as is the role of C.
      burnetii in livestock abortion. Q fever consistently accounts for a notable
      proportion of undifferentiated human febrile illness and infective endocarditis
      in cohort studies, but incidence estimates are lacking. C. burnetii presents a
      real yet underappreciated threat to human and animal health throughout Africa.

PMID- 24722556
TI  - Transcriptomic analysis of Petunia hybrida in response to salt stress using high
      throughput RNA sequencing.
AB  - Salinity and drought stress are the primary cause of crop losses worldwide. In
      sodic saline soils sodium chloride (NaCl) disrupts normal plant growth and
      development. The complex interactions of plant systems with abiotic stress have
      made RNA sequencing a more holistic and appealing approach to study transcriptome
      level responses in a single cell and/or tissue. In this work, we determined the
      Petunia transcriptome response to NaCl stress by sequencing leaf samples and
      assembling 196 million Illumina reads with Trinity software. Using our reference
      transcriptome we identified more than 7,000 genes that were differentially
      expressed within 24 h of acute NaCl stress. The proposed transcriptome can also
      be used as an excellent tool for biological and bioinformatics in the absence of
      an available Petunia genome and it is available at the SOL Genomics Network (SGN)
      http://solgenomics.net. Genes related to regulation of reactive oxygen species,
      transport, and signal transductions as well as novel and undescribed transcripts
      were among those differentially expressed in response to salt stress. The
      candidate genes identified in this study can be applied as markers for breeding
      or to genetically engineer plants to enhance salt tolerance. Gene Ontology
      analyses indicated that most of the NaCl damage happened at 24 h inducing
      genotoxicity, affecting transport and organelles due to the high concentration of
      Na+ ions. Finally, we report a modification to the library preparation protocol
      whereby cDNA samples were bar-coded with non-HPLC purified primers, without
      affecting the quality and quantity of the RNA-seq data. The methodological
      improvement presented here could substantially reduce the cost of sample
      preparation for future high-throughput RNA sequencing experiments.

PMID- 24722557
TI  - A comparative analysis of spatial Prisoner's Dilemma experiments: conditional
      cooperation and payoff irrelevance.
AB  - We have carried out a comparative analysis of data collected in three experiments
      on Prisoner's Dilemmas on lattices available in the literature. We focus on the
      different ways in which the behavior of human subjects can be interpreted, in
      order to empirically narrow down the possibilities for behavioral rules. Among
      the proposed update dynamics, we find that the experiments do not provide
      significant evidence for non-innovative game dynamics such as imitate-the-best or
      pairwise comparison rules, whereas moody conditional cooperation is supported by
      the data from all three experiments. This conclusion questions the applicability
      of many theoretical models that have been proposed to understand human behavior
      in spatial Prisoner's Dilemmas. A rule compatible with all our experiments, moody
      conditional cooperation, suggests that there is no detectable influence of
      interaction networks on the emergence of cooperation in behavioral experiments. 

PMID- 24722558
TI  - Prevalence and associated positive psychological variables of depression and
      anxiety among Chinese cervical cancer patients: a cross-sectional study.
AB  - BACKGROUND: The prevalence of depression and anxiety and its associated factors
      in cervical cancer are not well evaluated in China. Meanwhile, with increasing
      attention given to positive psychological variables in oncology field, there is a
      need to conduct a study to explore the integrative effects of positive
      psychological variables on depression/anxiety so as to provide patients a more
      holistic cancer care. The aim of this study was to assess the prevalence of
      depression/anxiety as well as the integrative effects of hope, optimism and
      general self-efficacy on depression/anxiety among Chinese cervical cancer
      patients. METHODS: A multi-centre, cross-sectional study was conducted of
      consecutive inpatients at the Liaoning Cancer Hospital & Institute and the
      Shengjing Hospital of China Medical University in Liaoning Province, northeast
      China. A total of 224 cervical cancer patients eligible for this study completed
      questionnaires on demographic and clinic variables, Hospital Anxiety and
      Depression Scale, Herth Hope Index, Life Orientation Scale-Revised, and General
      Self-Efficacy Scale during February and August 2013. RESULTS: The prevalence of
      depression and anxiety was 52.2% and 65.6% in cervical cancer patients. The
      anxiety score was significantly higher in patients at the period of 4-6 months
      after diagnose and at cancer stage II. Hierarchical regression analyses indicated
      that hope, optimism and general self-efficacy as a whole accounted for 31.3%
      variance of depression and 35.6% variance of anxiety. Under standardized estimate
      (beta) sequence, hope, optimism and general self-efficacy significantly
      associated with depression, respectively; hope and optimism were also significant
      individual predictors of anxiety. CONCLUSIONS: The high prevalence of depression
      and anxiety among cervical cancer patients should receive more attention in
      Chinese medical settings. More importantly, efforts to develop the integrated
      psychosocial interventions are effective and necessary to alleviate
      depression/anxiety in cervical cancer patients by synthesizing and integrating
      the individual protective effects of hope, optimism and general self-efficacy.

PMID- 24722559
TI  - Prevalence of radiographic osteoarthritis of the knee and its relationship to
      self-reported pain.
AB  - BACKGROUND AND AIM: Osteoarthritis (OA) of the knee is one of the most common
      skeletal disorders, yet little data are available in Asian populations. We sought
      to assess the prevalence and pattern of radiographic OA of the knee, and its
      relationship to self-reported pain in a Vietnamese population. METHODS: The study
      was based on a sample of 170 men and 488 women aged >=40 years who were randomly
      sampled from the Ho Chi Minh City (Vietnam). Radiographs of the knee were graded
      from 0 to 4 according to the Kellgren and Lawrence scale. Osteoarthritis was
      defined as being present in a knee if radiographic grades of 2 or higher were
      detected. Knee pain and symptoms were ascertained by direct interview using a
      structured questionnaire. RESULTS: The point prevalence of radiographic OA of the
      knee was 34.2%, with women having higher rate than men (35.3% vs 31.2%). The
      prevalence of knee OA increased with advancing age: 8% among those aged 40-49
      years, 30% in those aged 50-59 years, and 61.1% in those aged >=60 years. Greater
      BMI was associated with higher risk of knee OA. Self-reported knee pain was found
      in 35% of men and 62% of women. There was a statistically significant association
      between self-reported knee pain and knee OA (prevalence ratio 3.1; 95% CI 2.0 to
      4.6). CONCLUSIONS: These data indicate that approximately a third of Vietnamese
      men and women have radiographic OA in the knee, and that self-reported knee pain
      may be used as an indicator of knee osteoarthritis.

PMID- 24722560
TI  - Cytokine and clinical response to Saccharomyces boulardii therapy in diarrhea
      dominant irritable bowel syndrome: a randomized trial.
AB  - INTRODUCTION: This preliminary study aimed to investigate the effects of the
      probiotic Saccharomyces boulardii on proinflammatory and anti-inflammatory
      cytokines in patients with diarrhea-dominant irritable bowel syndrome (IBS-D).
      The other objectives were to document any clinical improvement as judged by
      symptoms, quality of life, and histology. PATIENTS AND METHODS: This was a
      randomized, double blind, placebo-controlled trial in which S. boulardii, 750
      mg/day, or placebo was administered for 6 weeks in IBS-D patients, in addition to
      ispaghula husk standard treatment. RESULTS: Thirty-seven patients received S.
      boulardii and 35 patients received the placebo. As compared with placebo, the S.
      boulardii group showed a significant decrease in blood and tissue levels of
      proinflammatory cytokines interleukin-8 (IL-8) and tumor necrosis factor-alpha
      (P<0.001) and an increase in anti-inflammatory IL-10 levels, as well as an
      increase in the tissue IL-10/IL-12 ratio (P<0.001). No significant change in the
      blood and tissue levels of cytokines was found in the placebo group. Bowel
      related IBS-D symptoms reported in the patients' daily diary improved in both
      groups. However, overall improvement in the quality of life was more marked in
      the S. boulardii group. Although baseline histological findings were mild, an
      improvement was observed in the probiotic group in the lymphocyte and neutrophil
      infiltrates (P=0.017 and 0.018), epithelial mitosis (P=0.003), and
      intraepithelial lymphocytes (P=0.024). No serious adverse events were found in
      either group. CONCLUSION: S. boulardii with ispaghula husk was superior to
      placebo with ispaghula husk in improving the cytokine profile, histology, and
      quality of life of patients with IBS-D. These preliminary results need to be
      confirmed in a well-powered trial.

PMID- 24722561
TI  - Biosimilars in the therapy of inflammatory bowel diseases.
AB  - A biosimilar is a copy of an approved biological medicine whose patent
      protections have expired. Biosimilars of antibodies to tumour necrosis factor
      alpha (TNFalpha) are becoming important in the treatment of inflammatory bowel
      diseases (IBD). The first one introduced commercially is an infliximab
      biosimilar. The aim of this study was to provide an overview of anti-TNFalpha
      biosimilars. The literature on biosimilars of monoclonal anti-TNFalpha antibodies
      was reviewed, including their manufacture and approval pathways, concerns about
      efficacy, safety, immunogenicity, extrapolation, switching and labelling.
      Previous experience with biosimilars of epoetin and other growth factors was also
      reviewed. The infliximab biosimilar CT-P13 was the first biosimilar monoclonal
      antibody registered for the treatment of IBD. The major advantage of biosimilars
      is the reduced cost of therapy. Concerns have arisen, however, about the efficacy
      and safety of CT-P13 in IBD, the extrapolation of results from rheumatologic
      trials to IBD and the free interchangeability of CT-P13 with infliximab.
      Experience with simple peptide biosimilars, such as epoetins and growth factors,
      has generally been positive, with these biosimilars having similar efficacy and
      safety as the original products, although immunogenicity remains a major concern.
      Upcoming postregistration studies will address concerns on biosimilars in IBD,
      including their efficacy, safety, immunogenicity, switching and
      interchangeability. Biosimilars active against the same epitopes, but with
      improved pharmacokinetic properties that enhance their efficacy and/or safety,
      may be the next stage in the development of biosimilars. Anti-TNFalpha
      biosimilars represent promising new treatment options for patients with IBD.
      However, data on their efficacy and safety in IBD are needed. 

PMID- 24722563
TI  - Contributions of contour frequency, amplitude, and luminance to the watercolor
      effect estimated by conjoint measurement.
AB  - The watercolor effect is a long-range, assimilative, filling-in phenomenon
      induced by a pair of distant, wavy contours of different chromaticities. Here, we
      measured joint influences of the contour frequency and amplitude and the
      luminance of the interior contour on the strength of the effect. Contour pairs,
      each enclosing a circular region, were presented with two of the dimensions
      varying independently across trials (luminance/frequency, luminance/amplitude,
      frequency/amplitude) in a conjoint measurement paradigm (Luce & Tukey, 1964). In
      each trial, observers judged which of the stimuli evoked the strongest fill-in
      color. Control stimuli were identical except that the contours were intertwined
      and generated little filling-in. Perceptual scales were estimated by a maximum
      likelihood method (Ho, Landy, & Maloney, 2008). An additive model accounted for
      the joint contributions of any pair of dimensions. As shown previously using
      difference scaling (Devinck & Knoblauch, 2012), the strength increases with
      luminance of the interior contour. The strength of the phenomenon was nearly
      independent of the amplitude of modulation of the contour but increased with its
      frequency up to an asymptotic level. On average, the strength of the effect was
      similar along a given dimension regardless of the other dimension with which it
      was paired, demonstrating consistency of the underlying estimated perceptual
      scales. 

PMID- 24722562
TI  - Combining spatial and temporal expectations to improve visual perception.
AB  - The importance of temporal expectations in modulating perceptual functions is
      increasingly recognized. However, the means through which temporal expectations
      can bias perceptual information processing remains ill understood. Recent
      theories propose that modulatory effects of temporal expectations rely on the co
      existence of other biases based on receptive-field properties, such as spatial
      location. We tested whether perceptual benefits of temporal expectations in a
      perceptually demanding psychophysical task depended on the presence of spatial
      expectations. Foveally presented symbolic arrow cues indicated simultaneously
      where (location) and when (time) target events were more likely to occur. The
      direction of the arrow indicated target location (80% validity), while its color
      (pink or blue) indicated the interval (80% validity) for target appearance. Our
      results confirmed a strong synergistic interaction between temporal and spatial
      expectations in enhancing visual discrimination. Temporal expectation
      significantly boosted the effectiveness of spatial expectation in sharpening
      perception. However, benefits for temporal expectation disappeared when targets
      occurred at unattended locations. Our findings suggest that anticipated receptive
      field properties of targets provide a natural template upon which temporal
      expectations can operate in order to help prioritize goal-relevant events from
      early perceptual stages. 

PMID- 24722565
TI  - Toxicity and metabolism of layered double hydroxide intercalated with levodopa in
      a Parkinson's disease model.
AB  - Layered hydroxide nanoparticles are generally biocompatible, and less toxic than
      most inorganic nanoparticles, making them an acceptable alternative drug delivery
      system. Due to growing concern over animal welfare and the expense of in vivo
      experiments both the public and the government are interested to find
      alternatives to animal testing. The toxicity potential of zinc aluminum layered
      hydroxide (ZAL) nanocomposite containing anti-Parkinsonian agent may be
      determined using a PC 12 cell model. ZAL nanocomposite demonstrated a decreased
      cytotoxic effect when compared to levodopa on PC12 cells with more than 80% cell
      viability at 100 ug/mL compared to less than 20% cell viability in a direct
      levodopa exposure. Neither levodopa-loaded nanocomposite nor the un-intercalated
      nanocomposite disturbed the cytoskeletal structure of the neurogenic cells at
      their IC50 concentration. Levodopa metabolite (HVA) released from the
      nanocomposite demonstrated the slow sustained and controlled release character of
      layered hydroxide nanoparticles unlike the burst uptake and release system shown
      with pure levodopa treatment. 

PMID- 24722564
TI  - Genome wide identification of aberrant alternative splicing events in myotonic
      dystrophy type 2.
AB  - Myotonic dystrophy type 2 (DM2) is a genetic, autosomal dominant disease due to
      expansion of tetraplet (CCTG) repetitions in the first intron of the ZNF9/CNBP
      gene. DM2 is a multisystemic disorder affecting the skeletal muscle, the heart,
      the eye and the endocrine system. According to the proposed pathological
      mechanism, the expanded tetraplets have an RNA toxic effect, disrupting the
      splicing of many mRNAs. Thus, the identification of aberrantly spliced
      transcripts is instrumental for our understanding of the molecular mechanisms
      underpinning the disease. The aim of this study was the identification of new
      aberrant alternative splicing events in DM2 patients. By genome wide analysis of
      10 DM2 patients and 10 controls (CTR), we identified 273 alternative spliced
      exons in 218 genes. While many aberrant splicing events were already identified
      in the past, most were new. A subset of these events was validated by qPCR assays
      in 19 DM2 and 15 CTR subjects. To gain insight into the molecular pathways
      involving the identified aberrantly spliced genes, we performed a bioinformatics
      analysis with Ingenuity system. This analysis indicated a deregulation of
      development, cell survival, metabolism, calcium signaling and contractility. In
      conclusion, our genome wide analysis provided a database of aberrant splicing
      events in the skeletal muscle of DM2 patients. The affected genes are involved in
      numerous pathways and networks important for muscle physio-pathology, suggesting
      that the identified variants may contribute to DM2 pathogenesis. 

PMID- 24722566
TI  - Radioprotective and antioxidant effect of resveratrol in hippocampus by
      activating Sirt1.
AB  - Reactive oxygen species can lead to functional alterations in lipids, proteins,
      and nucleic acids, and an accumulation of ROS (Reactive oxygen species) is
      considered to be one factor that contributes to neurodegenerative changes. An
      increase in ROS production occurs following irradiation. Neuronal tissue is
      susceptible to oxidative stress because of its high oxygen consumption and modest
      antioxidant defenses. As a polyphenolic compound, resveratrol is frequently used
      as an activator of Sirt1 (Sirtuin 1). The present study was designed to explore
      the radioprotective and antioxidant effect of resveratrol on Sirt1 expression and
      activity induced by radiation and to provide a new target for the development of
      radiation protection drugs. Our results demonstrate that resveratrol inhibits
      apoptosis induced by radiation via the activation of Sirt1. We demonstrated an
      increase in Sirt1 mRNA that was present on 21 days of resveratrol treatment
      following irradiation in a concentration-dependent manner. Such mRNA increase was
      accompanied by an increase of Sirt1 protein and activity. Resveratrol effectively
      antagonized oxidation induced by irradiation, supporting its cellular ROS
      scavenging effect. These results provide evidence that the mitochondrial
      protection and the antioxidant effect of resveratrol contribute to metabolic
      activity. These data suggest that Sirt1 may play an important role to protect
      neurons from oxidative stress. 

PMID- 24722567
TI  - Neuroprotective effect of melatonin against kainic acid-induced oxidative injury
      in hippocampal slice culture of rats.
AB  - Endogenous melatonin is a known free radical scavenger that removes reactive
      oxygen species (ROS), thus, alleviating oxidative stress. The purpose of this
      study was to demonstrate its effect against kainic acid (KA)-induced oxidative
      stress in organotypic hippocampal slice cultures (OHSCs). To observe
      neuroprotective effects of melatonin, different concentrations (0.01, 0.1 and 1
      mM) of melatonin were administrated after KA treatment for 18 h in OHSCs of rat
      pups. Dose-response studies showed that neuronal cell death was significantly
      reduced after 0.1 and 1 mMU melatonin treatments based on propidium iodide (PI)
      uptake and cresyl violet staining. The dichlorofluorescein (DCF) fluorescence
      which indicates ROS formation decreased more in the melatonin-treated group than
      in the KA group. The expression of 5-lipoxigenase (5-LO) and caspase-3 were
      reduced in the melatonin-treated groups compared to the KA group. These results
      suggest that melatonin may be an effective agent against KA-induced oxidative
      stress in the OHSC model. 

PMID- 24722568
TI  - Leucyl-tRNA synthetase regulates lactation and cell proliferation via mTOR
      signaling in dairy cow mammary epithelial cells.
AB  - The role of LeuRS, an aminoacyl-tRNA synthetase, as an intracellular l-leucine
      sensor for the mTORC1 pathway has been the subject of much research recently.
      Despite this, the association between LeuRS and lactation in dairy cow mammary
      epithelial cells (DCMECs) remains unknown. In this study, we found that LeuRS
      expression in mammary gland tissue was significantly higher during lactation than
      pregnancy. Moreover, our data demonstrates that LeuRS is localized in the
      cytoplasm. Treatment with leucine increased DCMECs viability and proliferation,
      as well as mammalian target of rapamycin (mTOR), p-mTOR, ribosomal protein S6
      kinase 1 (S6K1), p-S6K1, beta-Casein, sterol regulatory element binding protein
      1c (SREBP-1c), glucose transporter 1 (GLUT1), and Cyclin D1 mRNA and protein
      expression. Secretion of lactose and triglyceride were also increased. siRNA
      mediated knockdown of LeuRS led to reduction in all of these processes. Based on
      these data, LeuRS up-regulates the mTOR pathway to promote proliferation and
      lactation of DCMECs in response to changes in the intracellular leucine
      concentration. 

PMID- 24722569
TI  - Triterpenoid saponin biosynthetic pathway profiling and candidate gene mining of
      the Ilex asprella root using RNA-Seq.
AB  - Ilex asprella, which contains abundant alpha-amyrin type triterpenoid saponins,
      is an anti-influenza herbal drug widely used in south China. In this work, we
      first analysed the transcriptome of the I. asprella root using RNA-Seq, which
      provided a dataset for functional gene mining. mRNA was isolated from the total
      RNA of the I. asprella root and reverse-transcribed into cDNA. Then, the cDNA
      library was sequenced using an Illumina HiSeqTM 2000, which generated 55,028,452
      clean reads. De novo assembly of these reads generated 51,865 unigenes, in which
      39,269 unigenes were annotated (75.71% yield). According to the structures of the
      triterpenoid saponins of I. asprella, a putative biosynthetic pathway downstream
      of 2,3-oxidosqualene was proposed and candidate unigenes in the transcriptome
      data that were potentially involved in the pathway were screened using homology
      based BLAST and phylogenetic analysis. Further amplification and functional
      analysis of these putative unigenes will provide insight into the biosynthesis of
      Ilex triterpenoid saponins. 

PMID- 24722570
TI  - Cardiac Fas-dependent and mitochondria-dependent apoptosis after chronic cocaine
      abuse.
AB  - To evaluate whether chronic cocaine abuse will increase cardiac Fas-dependent and
      mitochondria-dependent apoptotic pathways, thirty-two male Wistar rats at 3-4
      months of age were randomly divided into a vehicle-treated group (phosphate
      buffered saline, PBS, 0.5 mL, SQ per day) and a cocaine-treated group (Cocaine,
      10 mg/kg, SQ per day). After 3 months of treatment, the excised left ventricles
      were measured by H&E staining, Western blotting, DAPI staining and TUNEL assays.
      More cardiac TUNEL-positive apoptotic cells were observed in the Cocaine group
      than the PBS group. Protein levels of TNF-alpha, Fas ligand, Fas death receptor,
      FADD, activated caspase-8, and activated caspase-3 (Fas-dependent apoptosis)
      extracted from excised hearts in the Cocaine group were significantly increased,
      compared to the PBS group. Protein levels of cardiac Bax, cytosolic cytochrome c,
      t-Bid-to-Bid, Bak-to-Bcl-xL, Bax-to-Bcl-2 ratio, activated caspase-9, and
      activated caspase-3 (mitochondria-dependent apoptosis) were significantly
      increased in the Cocaine group, compared to the PBS group. Chronic cocaine
      exposure appeared to activate the cardiac Fas-dependent and mitochondria
      dependent apoptosis, which may indicate a possible mechanism for the development
      of cardiac abnormalities in humans with chronic cocaine abuse. 

PMID- 24722571
TI  - Oxidative stress in cardiovascular disease.
AB  - In the special issue "Oxidative Stress in Cardiovascular Disease" authors were
      invited to submit papers that investigate key questions in the field of
      cardiovascular free radical biology. The original research articles included in
      this issue provide important information regarding novel aspects of reactive
      oxygen species (ROS)-mediated signaling, which have important implications in
      physiological and pathophysiological cardiovascular processes. The issue also
      included a number of review articles that highlight areas of intense research in
      the fields of free radical biology and cardiovascular medicine. 

PMID- 24722572
TI  - The hydraulic mechanism of the unfolding of hind wings in Dorcus titanus
      platymelus (order: Coleoptera).
AB  - In most beetles, the hind wings are thin and fragile; when at rest, they are held
      over the back of the beetle. When the hind wing unfolds, it provides the
      necessary aerodynamic forces for flight. In this paper, we investigate the
      hydraulic mechanism of the unfolding process of the hind wings in Dorcus titanus
      platymelus (Oder: Coleoptera). The wing unfolding process of Dorcus titanus
      platymelus was examined using high speed camera sequences (400 frames/s), and the
      hydraulic pressure in the veins was measured with a biological pressure sensor
      and dynamic signal acquisition and analysis (DSA) during the expansion process.
      We found that the total time for the release of hydraulic pressure during wing
      folding is longer than the time required for unfolding. The pressure is
      proportional to the length of the wings and the body mass of the beetle. A
      retinal camera was used to investigate the fluid direction. We found that the
      peak pressures correspond to two main cross-folding joint expansions in the hind
      wing. These observations strongly suggest that blood pressure facilitates the
      extension of hind wings during unfolding. 

PMID- 24722573
TI  - Vasostatin inhibits VEGF-induced endothelial cell proliferation, tube formation
      and induces cell apoptosis under oxygen deprivation.
AB  - Anti-angiogenesis treatment has been a promising new form of cancer therapy.
      Endothelial cells are critical for vascular homeostasis and play important roles
      in angiogenesis, vascular and tissue remodeling. Vasostatin, the 180 amino acid N
      terminal fragment of the calreticulin protein, is reported to be a potent
      endogenous inhibitor of angiogenesis, suppressing tumor growth. However, the
      mechanism of these effects has not been sufficiently investigated. This study was
      performed to investigate the possible mechanism of vasostatin effects on primary
      cultured human umbilical vein endothelial cells (HUVEC). We found that vasostatin
      could inhibit the cell viability of HUVEC and induce cell apoptosis through
      mitochondrial pathways via activation of caspase-3 under oxygen deprivation
      conditions. Meanwhile, vasostatin also inhibited vascular endothelial growth
      factor-induced proliferation and tube formation of HUVEC. The possible mechanism
      of vasostatin-inhibited proliferation of HUVEC could be through down-regulation
      of endothelial nitric oxide synthase. These findings suggest that vasostatin
      could regulate endothelial cell function and might be used in anti-angiogenesis
      treatment. 

PMID- 24722574
TI  - Lubiprostone for chronic constipation in adults.
AB  - Lubiprostone (Amitiza-Sucampo Pharma Europe), a chloride-channel activator is
      licensed for the treatment of chronic idiopathic constipation in adults. It
      received a marketing authorisation in the UK in September 2012. In this article,
      we consider the evidence for lubiprostone in the management of constipation and
      how the treatment fits with current management strategies for constipation. 

PMID- 24722575
TI  - Management of adults with PTSD part II: drugs and other interventions.
AB  - Exposure to traumatic events is common, and many people experience some symptoms
      following such exposure. In most people, these symptoms subside within a few
      weeks, but for others, post-traumatic stress disorder (PTSD) develops and may be
      long-lasting. Part I of this article (DTB 2014; 52: 33-6) discussed the
      recognition of PTSD and evidence for trauma-focused psychological treatment
      (generally considered to be first-line treatment). Here in part II of the
      article, we discuss other possible second-line options: pharmacological
      treatments and other therapies. 

PMID- 24722576
TI  - Titanium (III) cation selective electrode based on synthesized tris(2pyridyl)
      methylamine ionophore and its application in water samples.
AB  - The introduction of low detection limit ion selective electrodes (ISEs) may well
      pave the way for the determination of trace targets of cationic compounds. This
      research focuses on the detection of titanium (III) cation using a new PVC
      membrane sensor based on synthesized tris(2pyridyl) methylamine (tpm) ionophore.
      The application and validation of the proposed sensor was done using
      potentiometric titration, inductively coupled plasma atomic emission spectrometry
      (ICP-AES), and atomic absorption spectrometry (AAS). The membrane sensor
      exhibited a Nernstian response to the titanium (III) cation over a concentration
      range of 1.0 * 10(-6)-1.0 * 10(-2) M and pH range from 1-2.5. The Nernstian
      slope, the lower of detection (LOD), and the response time (t95%) of the proposed
      sensor were 29.17 +/- 0.24 mV/dec, 7.9 * 10-7 M, and 20 s, respectively. The
      direct determination of 4-39 MUg/ml of titanium (III) standard solution showed an
      average recovery of 94.60 and a mean relative standard deviation of 1.8 at 100.0
      MUg/ml. Finally, the utilization of the electrodes as end-point indicators for
      potentiometric titration with EDTA solutions for titanium (III) sensor was
      successfully carried out.

PMID- 24722577
TI  - Coupled flip-flop model for REM sleep regulation in the rat.
AB  - Recent experimental studies investigating the neuronal regulation of rapid eye
      movement (REM) sleep have identified mutually inhibitory synaptic projections
      among REM sleep-promoting (REM-on) and REM sleep-inhibiting (REM-off) neuronal
      populations that act to maintain the REM sleep state and control its onset and
      offset. The control mechanism of mutually inhibitory synaptic interactions
      mirrors the proposed flip-flop switch for sleep-wake regulation consisting of
      mutually inhibitory synaptic projections between wake- and sleep-promoting
      neuronal populations. While a number of synaptic projections have been identified
      between these REM-on/REM-off populations and wake/sleep-promoting populations,
      the specific interactions that govern behavioral state transitions have not been
      completely determined. Using a minimal mathematical model, we investigated
      behavioral state transition dynamics dictated by a system of coupled flip-flops,
      one to control transitions between wake and sleep states, and another to control
      transitions into and out of REM sleep. The model describes the neurotransmitter
      mediated inhibitory interactions between a wake- and sleep-promoting population,
      and between a REM-on and REM-off population. We proposed interactions between the
      wake/sleep and REM-on/REM-off flip-flops to replicate the behavioral state
      statistics and probabilities of behavioral state transitions measured from
      experimental recordings of rat sleep under ad libitum conditions and after 24 h
      of REM sleep deprivation. Reliable transitions from REM sleep to wake, as
      dictated by the data, indicated the necessity of an excitatory projection from
      the REM-on population to the wake-promoting population. To replicate the increase
      in REM-wake-REM transitions observed after 24 h REM sleep deprivation required
      that this excitatory projection promote transient activation of the wake
      promoting population. Obtaining the reliable wake-nonREM sleep transitions
      observed in the data required that activity of the wake-promoting population
      modulated the interaction between the REM-on and REM-off populations. This
      analysis suggests neuronal processes to be targeted in further experimental
      studies of the regulatory mechanisms of REM sleep. 

PMID- 24722578
TI  - MYT3, a Myb-like transcription factor, affects fungal development and
      pathogenicity of Fusarium graminearum.
AB  - We previously characterized members of the Myb protein family, MYT1 and MYT2, in
      Fusarium graminearum. MYT1 and MYT2 are involved in female fertility and
      perithecium size, respectively. To expand knowledge of Myb proteins in F.
      graminearum, in this study, we characterized the functions of the MYT3 gene,
      which encodes a putative Myb-like transcription factor containing two Myb DNA
      binding domains and is conserved in the subphylum Pezizomycotina of Ascomycota.
      MYT3 proteins were localized in nuclei during most developmental stages,
      suggesting the role of MYT3 as a transcriptional regulator. Deletion of MYT3
      resulted in impairment of conidiation, germination, and vegetative growth
      compared to the wild type, whereas complementation of MYT3 restored the wild-type
      phenotype. Additionally, the Deltamyt3 strain grew poorly on nitrogen-limited
      media; however, the mutant grew robustly on minimal media supplemented with
      ammonium. Moreover, expression level of nitrate reductase gene in the Deltamyt3
      strain was decreased in comparison to the wild type and complemented strain. On
      flowering wheat heads, the Deltamyt3 strain exhibited reduced pathogenicity,
      which corresponded with significant reductions in trichothecene production and
      transcript levels of trichothecene biosynthetic genes. When the mutant was
      selfed, mated as a female, or mated as a male for sexual development, perithecia
      were not observed on the cultures, indicating that the Deltamyt3 strain lost both
      male and female fertility. Taken together, these results demonstrate that MYT3 is
      required for pathogenesis and sexual development in F. graminearum, and will
      provide a robust foundation to establish the regulatory networks for all Myb-like
      proteins in F. graminearum. 

PMID- 24722579
TI  - An electrochemiluminescent microRNA biosensor based on hybridization chain
      reaction coupled with hemin as the signal enhancer.
AB  - In this study, a new universal biosensor based on luminol anodic
      electrochemiluminescence (ECL) for the detection of microRNA-155 was constructed
      by using hydrogen peroxide (H2O2) as a co-reactant and hemin as a catalyzer for
      signal amplification. The bare glassy carbon electrode (GCE) was first
      electrodeposited with Au nanoparticles (AuNPs). Then, helper DNA, which was
      partly complementary with the hairpin DNA chains, was assembled on the prepared
      GCE. Target microRNA-155 and the hairpin hybridization chains could create a
      formation of extended double-stranded DNA (dsDNA) polymers through the
      displacement of hybridization chains and the hybridization chain reaction (HCR).
      The HCR-generated dsDNA polymers give rise to the intercalation of a lot of hemin
      which could catalyze the oxidation of H2O2, leading to a remarkably amplified ECL
      signal output. The proposed biosensor showed a wide linear range from 5 fM to 50
      pM with a relatively low detection limit of 1.67 fM for microRNA-155 detection.
      With excellent selectivity, good stability and high sensitivity, the proposed
      biosensor is promising in the development of a high-throughput assay of microRNA
      155. 

PMID- 24722580
TI  - Gonadotropin-releasing hormone agonists sensitize, and resensitize, prostate
      cancer cells to docetaxel in a p53-dependent manner.
AB  - Gonadotropin-releasing hormone (GnRH) receptors are expressed in prostate cancer,
      specifically in the most aggressive stage of the tumor (castration-resistant
      prostate cancer, CRPC) for which the standard treatment, docetaxel-based
      chemotherapy, can only improve the median survival time by few months. We
      previously showed that GnRH agonists exert an antitumor activity in CRPC cells;
      however, a link between GnRH receptors and the apoptotic machinery remains to be
      defined. Aim of this study was to evaluate whether, in CRPC cells, GnRH agonists
      might affect the expression/activity of apoptosis-related proteins and might
      sensitize, or resensitize, cancer cells to chemotherapeutics. We demonstrated
      that, in p53-positive DU145 cells, GnRH agonists: a) increase the expression of
      the proapoptotic protein Bax; this effect is mediated by the phosphorylation
      (activation) of p53, triggered by the p38 MAPK; b) potentiate the
      antiproliferative/proapoptotic activity of docetaxel; c) resensitize docetaxel
      resistant cells to the antitumor activity of the cytotoxic drug. These data
      indicate that GnRH agonists sensitize and, more importantly, resensitize DU145
      CRPC cells to chemotherapy in a p53-dependent manner. To confirm the crucial role
      of p53 in the activity of GnRH agonists, experiments were performed in p53-null
      PC3 cells. We found that GnRH agonists fail to increase Bax expression and do not
      potentiate the cytotoxic activity of docetaxel. These results may provide a
      rationale for novel combination treatment strategies, especially for docetaxel
      resistant CRPC patients expressing a functional p53 protein. 

PMID- 24722581
TI  - Evaluation of three-dimensional biofilms on antibacterial bonding agents
      containing novel quaternary ammonium methacrylates.
AB  - Antibacterial adhesives are promising to inhibit biofilms and secondary caries.
      The objectives of this study were to synthesize and incorporate quaternary
      ammonium methacrylates into adhesives, and investigate the alkyl chain length
      effects on three-dimensional biofilms adherent on adhesives for the first time.
      Six quaternary ammonium methacrylates with chain lengths of 3, 6, 9, 12, 16 and
      18 were synthesized and incorporated into Scotchbond Multi-Purpose. Streptococcus
      mutans bacteria were cultured on resin to form biofilms. Confocal laser scanning
      microscopy was used to measure biofilm thickness, live/dead volumes and live
      bacteria percentage vs. distance from resin surface. Biofilm thickness was the
      greatest for Scotchbond control; it decreased with increasing chain length,
      reaching a minimum at chain length 16. Live-biofilm volume had a similar trend.
      Dead-biofilm volume increased with increasing chain length. The adhesive with
      chain length 9 had 37% live bacteria near resin surface, but close to 100% live
      bacteria in the biofilm top section. For chain length 16, there were nearly 0%
      live bacteria throughout the three-dimensional biofilm. In conclusion, strong
      antibacterial activity was achieved by adding quaternary ammonium into adhesive,
      with biofilm thickness and live-biofilm volume decreasing as chain length was
      increased from 3 to 16. Antibacterial adhesives typically only inhibited bacteria
      close to its surface; however, adhesive with chain length 16 had mostly dead
      bacteria in the entire three-dimensional biofilm. Antibacterial adhesive with
      chain length 16 is promising to inhibit biofilms at the margins and combat
      secondary caries. 

PMID- 24722582
TI  - Comparative study of chitosan/fibroin-hydroxyapatite and collagen membranes for
      guided bone regeneration in rat calvarial defects: micro-computed tomography
      analysis.
AB  - This study aimed to utilize micro-computed tomography (micro-CT) analysis to
      compare new bone formation in rat calvarial defects using chitosan/fibroin
      hydroxyapatite (CFB-HAP) or collagen (Bio-Gide) membranes. Fifty-four (54) rats
      were studied. A circular bony defect (8 mm diameter) was formed in the centre of
      the calvaria using a trephine bur. The CFB-HAP membrane was prepared by thermally
      induced phase separation. In the experimental group (n=18), the CFB-HAP membrane
      was used to cover the bony defect, and in the control group (n=18), a resorbable
      collagen membrane (Bio-Gide) was used. In the negative control group (n=18), no
      membrane was used. In each group, six animals were euthanized at 2, 4 and 8 weeks
      after surgery. The specimens were then analysed using micro-CT. There were
      significant differences in bone volume (BV) and bone mineral density (BMD)
      (P<0.05) between the negative control group and the membrane groups. However,
      there were no significant differences between the CFB-HAP group and the collagen
      group. We concluded that the CFB-HAP membrane has significant potential as a
      guided bone regeneration (GBR) membrane. 

PMID- 24722583
TI  - Exploring homo-FRET to quantify the oligomer stoichiometry of membrane-bound
      proteins involved in a cooperative partition equilibrium.
AB  - The establishment of protein-protein interactions between membrane-bound proteins
      is associated with several biological functions and dysfunctions. Here, an
      analytical framework that uses energy homo transfer to directly probe
      quantitatively the oligomerization state of membrane-bound proteins engaged in a
      three-state cooperative partition is presented. Briefly, this model assumes that
      monomeric protein molecules partition into the bilayer surface and reversibly
      assemble into oligomers with k subunits. A general equation relating the overall
      steady-state fluorescence anisotropy of the sample to its fractional labeling was
      derived by considering explicitly that the anisotropy of mixed oligomers
      containing i-labeled monomers is inversely proportional to the number of labeled
      subunits per oligomer (Runnels and Scarlata limit). This method was very robust
      in describing the electrostatic interaction of Alexa Fluor 488 fluorescently
      labeled lysozyme (Lz-A488) with phosphatidylserine-containing membranes. The
      pronounced decrease detected in the fluorescence anisotropy of Lz-A488 always
      correlated with the system reaching a high membrane surface density of the
      protein (at a low lipid-to-protein (L/P) molar ratio). The occurrence of energy
      homo transfer-induced fluorescence depolarization was further confirmed by
      measuring the anisotropy decays of Lz-A488 under these conditions. A global
      analysis of the steady-state anisotropy data obtained under a wide range of
      experimental conditions (variable anionic lipid content of the liposomes, L/P
      molar ratios and protein fractional labeling) confirmed that membrane-bound Lz
      A488 assembled into oligomeric complexes, possibly with a stoichiometry of k = 6
      +/- 1. This study illustrates that even in the presence of a coupled partition
      oligomerization equilibrium, steady-state anisotropy measurements provide a
      simple and reliable tool to monitor the self-assembly of membrane-bound proteins.

PMID- 24722584
TI  - The HMW1C-like glycosyltransferases--an enzyme family with a sweet tooth for
      simple sugars.

PMID- 24722585
TI  - Limiting nuclearity in formation of polynuclear metal complexes through [2 + 3]
      cycloaddition: synthesis and magnetic properties of tri- and pentanuclear metal
      complexes.
AB  - A tridentate ligand p-chloro-2-{(2-(dimethylamino)ethylimino)methyl}phenol (HL)
      was used to generate an octahedral nickel complex [Ni(L)Cl(H2O)2] 1 which was
      further converted into a square-planar nickel complex [Ni(L)(N3)] 2. The [2 + 3]
      cycloaddition reaction between metal coordinated azide 2 and different
      organonitriles under microwave irradiation afforded tri- and pentanuclear
      nickel(II) complexes 4a-4c. Reaction with benzonitrile and 3-cyano pyridine
      furnished the trinuclear species [Ni3L2(5-phenyltetrazolato)4(DMF)2] 4a and
      [Ni3L2{5-(3-pyridyl)-tetrazolato}4(DMF)2].2H2O 4b, respectively. The nickel
      centers were found to be linearly disposed to each other and the complex is
      formed by a 2,3-tetrazolate bridge and a phenoxo bridge between central and
      terminal nickel atoms. Compound 2 when treated with 1,2-dicyanobenzene under
      identical conditions furnished a pentanuclear complex [Ni5L4{5-(2-cyanophenyl)
      tetrazolato}4(OH)2(H2O)2].3H2O.DMF 4c. In this pentanuclear compound two dimeric
      nickel units are connected to the central nickel center by a MU3-hydroxo bridge
      and a tetrazolate ligand operating via a relatively rare 1,2,3-bridging mode. The
      compounds were characterized by IR, elemental analysis, thermogravimetric
      analysis and single crystal X-ray crystallography. The magnetic susceptibility
      data for compounds 4a-4c show dominant antiferromagnetic interactions between the
      nickel centers for all the complexes. DFT calculations were performed to
      investigate the magnetic parameter in one of the complexes 4b by a broken
      symmetry approach.

PMID- 24722586
TI  - Broad spectrum antiviral activity of favipiravir (T-705): protection from highly
      lethal inhalational Rift Valley Fever.
AB  - BACKGROUND: Development of antiviral drugs that have broad-spectrum activity
      against a number of viral infections would be of significant benefit. Due to the
      evolution of resistance to currently licensed antiviral drugs, development of
      novel anti-influenza drugs is in progress, including Favipiravir (T-705), which
      is currently in human clinical trials. T-705 displays broad-spectrum in vitro
      activity against a number of viruses, including Rift Valley Fever virus (RVFV).
      RVF is an important neglected tropical disease that causes human, agricultural,
      and economic losses in endemic regions. RVF has the capacity to emerge in new
      locations and also presents a potential bioterrorism threat. In the current
      study, the in vivo efficacy of T-705 was evaluated in Wistar-Furth rats infected
      with the virulent ZH501 strain of RVFV by the aerosol route.
      METHODOLOGY/PRINCIPAL FINDINGS: Wistar-Furth rats are highly susceptible to a
      rapidly lethal disease after parenteral or inhalational exposure to the
      pathogenic ZH501 strain of RVFV. In the current study, two experiments were
      performed: a dose-determination study and a delayed-treatment study. In both
      experiments, all untreated control rats succumbed to disease. Out of 72 total
      rats infected with RVFV and treated with T-705, only 6 succumbed to disease. The
      remaining 66 rats (92%) survived lethal infection with no significant weight loss
      or fever. The 6 treated rats that succumbed survived significantly longer before
      succumbing to encephalitic disease. CONCLUSIONS/SIGNIFICANCE: Currently, there
      are no licensed antiviral drugs for treating RVF. Here, T-705 showed remarkable
      efficacy in a highly lethal rat model of Rift Valley Fever, even when given up to
      48 hours post-infection. This is the first study to show protection of rats
      infected with the pathogenic ZH501 strain of RVFV. Our data suggest that T-705
      has potential to be a broad-spectrum antiviral drug.

PMID- 24722587
TI  - Host and bacterial proteins that repress recruitment of LC3 to Shigella early
      during infection.
AB  - Shigella spp. are intracytosolic gram-negative pathogens that cause disease by
      invasion and spread through the colonic mucosa, utilizing host cytoskeletal
      components to form propulsive actin tails. We have previously identified the host
      factor Toca-1 as being recruited to intracellular S. flexneri and being required
      for efficient bacterial actin tail formation. We show that at early times during
      infection (40 min.), the type three-secreted effector protein IcsB recruits Toca
      1 to intracellular bacteria and that recruitment of Toca-1 is associated with
      repression of recruitment of LC3, as well as with repression of recruitment of
      the autophagy marker NDP52, around these intracellular bacteria. LC3 is best
      characterized as a marker of autophagosomes, but also marks phagosomal membranes
      in the process LC3-associated phagocytosis. IcsB has previously been demonstrated
      to be required for S. flexneri evasion of autophagy at late times during
      infection (4-6 hr) by inhibiting binding of the autophagy protein Atg5 to the
      Shigella surface protein IcsA (VirG). Our results suggest that IcsB and Toca-1
      modulation of LC3 recruitment restricts LC3-associated phagocytosis and/or LC3
      recruitment to vacuolar membrane remnants. Together with published results, our
      findings suggest that IcsB inhibits innate immune responses in two distinct ways,
      first, by inhibiting LC3-associated phagocytosis and/or LC3 recruitment to
      vacuolar membrane remnants early during infection, and second, by inhibiting
      autophagy late during infection. 

PMID- 24722589
TI  - A novel DNA nanosensor based on CdSe/ZnS quantum dots and synthesized Fe3O4
      magnetic nanoparticles.
AB  - Although nanoparticle-enhanced biosensors have been extensively researched, few
      studies have systematically characterized the roles of nanoparticles in enhancing
      biosensor functionality. This paper describes a successful new method in which
      DNA binds directly to iron oxide nanoparticles for use in an optical biosensor. A
      wide variety of nanoparticles with different properties have found broad
      application in biosensors because their small physical size presents unique
      chemical, physical, and electronic properties that are different from those of
      bulk materials. Of all nanoparticles, magnetic nanoparticles are proving to be a
      versatile tool, an excellent case in point being in DNA bioassays, where magnetic
      nanoparticles are often used for optimization of the hybridization and separation
      of target DNA. A critical step in the successful construction of a DNA biosensor
      is the efficient attachment of biomolecules to the surface of magnetic
      nanoparticles. To date, most methods of synthesizing these nanoparticles have led
      to the formation of hydrophobic particles that require additional surface
      modifications. As a result, the surface to volume ratio decreases and nonspecific
      bindings may occur so that the sensitivity and efficiency of the device
      deteriorates. A new method of large-scale synthesis of iron oxide (Fe3O4)
      nanoparticles which results in the magnetite particles being in aqueous phase,
      was employed in this study. Small modifications were applied to design an optical
      DNA nanosensor based on sandwich hybridization. Characterization of the
      synthesized particles was carried out using a variety of techniques and CdSe/ZnS
      core-shell quantum dots were used as the reporter markers in a
      spectrofluorophotometer. We showed conclusively that DNA binds to the surface of
      ironoxide nanoparticles without further surface modifications and that these
      magnetic nanoparticles can be efficiently utilized as biomolecule carriers in
      biosensing devices. 

PMID- 24722588
TI  - Regeneration of Aplysia bag cell neurons is synergistically enhanced by substrate
      bound hemolymph proteins and laminin.
AB  - We have investigated Aplysia hemolymph as a source of endogenous factors to
      promote regeneration of bag cell neurons. We describe a novel synergistic effect
      between substrate-bound hemolymph proteins and laminin. This combination
      increased outgrowth and branching relative to either laminin or hemolymph alone.
      Notably, the addition of hemolymph to laminin substrates accelerated growth cone
      migration rate over ten-fold. Our results indicate that the active factor is
      either a high molecular weight protein or protein complex and is not the
      respiratory protein hemocyanin. Substrate-bound factor(s) from central nervous
      system-conditioned media also had a synergistic effect with laminin, suggesting a
      possible cooperation between humoral proteins and nervous system extracellular
      matrix. Further molecular characterization of active factors and their cellular
      targets is warranted on account of the magnitude of the effects reported here and
      their potential relevance for nervous system repair. 

PMID- 24722590
TI  - Rapid identification of antioxidant compounds of Genista saharae Coss. & Dur. by
      combination of DPPH scavenging assay and HPTLC-MS.
AB  - Genista species are sources of antioxidant phenolic compounds such as O- and C
      glycosylflavonoids and isoflavonoids. A combination of a DPPH scavenging assay
      with HPTLC-MS, a fast and efficient method for identification of bioactive
      compounds, has been applied for evaluation of the radical scavenging activity of
      metabolites from Genista saharae Coss. & Dur. Different organs collected at
      various periods have been compared. Identification of antioxidant compounds was
      obtained by elution of the major DPPH-inhibition zones. The resulting HPTLC-MS
      analysis under moderately polar conditions, coupled to the DPPH results led to
      the putative identification of two antioxidant isoflavone aglycones: 3',4',5,7
      tetrahydroxyisoflavone (1) and ficuisoflavone (3), whereas polar migration
      conditions led to the identification of the glycosides 5-methoxy-4',7-trihydroxy
      8-glucopyranosylisoflavone (4) and 4',5-dihydroxy-7-methoxyisoflavone-4'-O-beta-D
      gluco-pyranoside (5). Evaluation of percentage of inhibition of DPPH radical by
      the purified isoflavone 4 from the root extract showed that it affords a moderate
      contribution to the total radical scavenging activity of the extract. 

PMID- 24722591
TI  - Synthesis and biological evaluation of novel 2-methoxypyridylamino-substituted
      riminophenazine derivatives as antituberculosis agents.
AB  - Clofazimine, a member of the riminophenazine class, is one of the few antibiotics
      that are still active against multidrug-resistant Mycobacterium tuberculosis (M.
      tuberculosis). However, the clinical utility of this agent is limited by its
      undesirable physicochemical properties and skin pigmentation potential. With the
      goal of maintaining potent antituberculosis activity while improving
      physicochemical properties and lowering skin pigmentation potential, a series of
      novel riminophenazine derivatives containing a 2-methoxypyridylamino substituent
      at the C-2 position of the phenazine nucleus were designed and synthesized. These
      compounds were evaluated for antituberculosis activity against M. tuberculosis
      H37Rv and screened for cytotoxicity. Riminophenazines bearing a 3-halogen- or 3,4
      dihalogen-substituted phenyl group at the N-5 position exhibited potent
      antituberculosis activity, with MICs ranging from 0.25~0.01 MUg/mL. The 3,4
      dihalogen- substituted compounds displayed low cytotoxicity, with IC50 values
      greater than 64 MUg/mL. Among these riminophenazines, compound 15 exhibited
      equivalent in vivo efficacy against M. tuberculosis infection and reduced skin
      discoloration potential in an experimental mouse infection model as compared to
      clofazimine. Compound 15, as compared to clofazimine, also demonstrated improved
      physicochemical properties and pharmacokinetic profiles with a short half-life
      and less drug tissue accumulation. This compound is being evaluated as a
      potential drug candidate for the treatment of multidrug resistant tuberculosis. 

PMID- 24722592
TI  - Vitamin D deficiency and leisure time activities in the elderly: are all pastimes
      the same?
AB  - BACKGROUND: Optimal vitamin D status is important for overall health and well
      being, particularly in the elderly. Although vitamin D synthesis in the skin
      declines with age, exposure to sunlight still seems to help older-aged adults to
      achieve adequate serum 25-hydroxyvitamin D (25OHD) levels. Elderly people would
      therefore benefit from outdoor leisure activities, but the effects of different
      types of pastime on serum 25OHD levels have yet to be thoroughly investigated.
      AIMS: To assess the association of different pastimes with 25OHD deficiency in
      elderly subjects. METHODS: A sample of 2,349 community-dwelling elderly
      individuals (1,389 females and 960 males) enrolled in the Progetto Veneto Anziani
      was analyzed. Brisk walking, cycling, gardening and fishing were classed as
      outdoor activities, and dancing and gym workouts as indoor pastimes. Any
      activities undertaken for at least 1 hour/week during the previous month were
      considered as being practiced regularly. Logistic regression models were used to
      estimate the association between different pastimes and 25OHD deficiency.
      RESULTS: Serum 25OHD levels were significantly higher in individuals who engaged
      in outdoor pastimes (+25% in women, +27.7% in men) compared to those who did not.
      In particular, subjects regularly practicing gardening or cycling had higher
      serum 25OHD levels than those who did not, whereas 25OHD levels differed little
      between subjects who did or did not undertake indoor activities. Among the
      outdoor pastimes considered, logistic regression analysis confirmed a lower
      likelihood of vitamin D deficiency (25OHD<50 nmol/L) for cyclists (OR 0.51, 95%
      CI 0.37-0.69 in women; OR 0.50, 95% CI 0.29-0.87 in men) and gardeners (OR 0.62,
      95% CI 0.47-0.83 in women; OR 0.46, 95% CI 0.26-0.80), but not for brisk walkers.
      CONCLUSIONS: Regular cycling and gardening reduce the likelihood of inadequate
      vitamin D status in Caucasian elderly people, irrespective of their age, BMI and
      comorbidities, and of the season of the year.

PMID- 24722594
TI  - Defra publishes its strategy for achieving TB-free status for England.

PMID- 24722593
TI  - Pilot badger culls to continue--but no wider roll out.

PMID- 24722595
TI  - Mis-stunning 'extremely rare' in British slaughterhouses.

PMID- 24722598
TI  - CVOs quizzed on the 'big issues'.

PMID- 24722599
TI  - BVA President mans up for hantavirus research project.

PMID- 24722602
TI  - Sudden death of calves related to anticipation of feeding.

PMID- 24722603
TI  - Schmallenberg virus: responding to disease emergence in real time.

PMID- 24722604
TI  - Mycobacterium bovis infection in cats and people.

PMID- 24722605
TI  - Mycobacterium bovis infection in cats and people.

PMID- 24722606
TI  - Protocol for medicated feedstuffs.

PMID- 24722607
TI  - Enteric redmouth disease in rainbow trout: an affair of the heart?

PMID- 24722608
TI  - Future of the RCVS fellowship.

PMID- 24722609
TI  - Evidence-based practice and contextual care.

PMID- 24722610
TI  - Science fiction inspires innovation.

PMID- 24722611
TI  - Impact of healing touch with healing harp on inpatient acute care pain: a
      retrospective analysis.
AB  - This study examined the concomitant use of 2 complementary and alternative
      medicine modalities, Healing Harp and Healing Touch, to reduce pain, anxiety, and
      nausea in the postoperative patient population. The results demonstrate the
      effectiveness of using concomitant Healing Touch and Healing Harp to
      significantly reduce moderate to severe pain and anxiety in this patient
      population. Further research is warranted.

PMID- 24722612
TI  - Feldenkrais method empowers adults with chronic back pain.
AB  - A phenomenological approach was used to explore the experiences of 11 adults
      attending Awareness Through Movement lessons in the Feldenkrais Method to manage
      chronic-episodic back pain. Semistructured interviews were analyzed. The results
      suggest improving self-efficacy through somatic education and awareness
      potentially offers a way forward given the back pain epidemic. 

PMID- 24722613
TI  - Auricular point acupressure for chronic pain: a feasibility study of a 4-week
      treatment protocol.
AB  - This 1-group, 4-week observational study aimed to (1) assess the feasibility of
      recruiting, retention, and completion of a 4-week auricular point acupressure
      (APA) treatment protocol for chronic pain in adult patients and (2) assess the
      effects of APA in pain reduction (pain severity and pain interference) among
      these patients. The participants received a 4-week APA treatment protocol in
      weekly cycles. Each weekly cycle included 5 days with APA seeds taped onto the
      ear and 2 days without. Each participant was called every day to monitor
      adherence to the treatment protocol (the actual times the participant pressed the
      seeds each day and the duration of applied pressure), to answer analgesic use,
      and to answer the pain intensity questionnaire. Thirty participants were
      initially enrolled in this study, but 5 did not continue. The retention rate was
      83% (n = 25). Approximately 60% of the participants (n = 15) adhered to the 4
      week APA and completed all data assessments. At baseline assessment, only 40% of
      all participants (n = 12 of 30) were confident that APA would reduce and
      eliminate pain; nonetheless, all participants reported fewer episodes of pain
      occurrences and pain intensity with the APA treatment. For the participants who
      completed the 4-week APA protocol (n = 15), 96% (n = 14) decreased analgesic
      medication intake and 88% (n = 13) felt "much better" after the APA treatment.
      Participants reported an average reduction of 63% in the worst pain intensity at
      day 7. By the end of the 4-week APA protocol, an even greater reduction in pain
      intensity was reported (66%, n = 10, at day 28). The participants who did not
      complete the treatment protocol reported an average pain reduction of 29%, which
      fluctuated to 22% before they dropped out. Auricular point acupressure is
      feasible for patients with chronic pain. The preliminary findings of this
      feasibility study show a reduction in pain intensity and improvement in physical
      function, which demonstrate the potential for APA as a treatment option for
      patients with chronic pain.

PMID- 24722614
TI  - Bowel movement: the sixth vital sign.
AB  - Bowel movements provide vital information on how the body is functioning, and
      constipation among older adults is especially problematic. Although we do not
      like hearing the details of someone else's bowel movement, it is a function that
      nurses need to assess, support, and treat with the same attitude as when caring
      for patients with pain. 

PMID- 24722615
TI  - Traditional practices used by Turkish mothers in the care of their babies.
AB  - This descriptive study was conducted to determine the traditional practices used
      by 1410 mothers in the care of their babies in Eskisehir, Turkey. The results of
      the present study suggest that traditional practices, which sometimes may be
      hazardous or beneficial, are widely used by Turkish mothers. We recommend that
      families should be informed about the possible hazardous effects of some
      traditional practices, however the non-hazardous and beneficial practices
      providing spiritual well-being may be supported. The optimal strategy is to teach
      mothers this information during the pregnancy period. 

PMID- 24722616
TI  - Predictors of adolescent health risk behaviors.
AB  - The aim of this study was to determine the predictors of health risk behaviors of
      adolescents. A cross-sectional and descriptive design was used. A convenience
      sample of 436 undergraduate students was recruited from departments and faculties
      of Ataturk University. The researcher visited university departments 5 working
      days each week to conduct interviews with the students. The students were asked
      to complete a questionnaire in their classrooms. The data analysis used
      multivariate testing to identify predictors of health risk behaviors. The mean
      score on the health risk behavior scale indicated that the participants sometimes
      engaged in risky behaviors concerning diet, anger, stress, and disease
      prevention. The adolescents frequently engaged in risky behavior concerning
      medical compliance and beliefs about masculinity. Demographically, age, gender,
      income, and education level of demographic characteristics of the adolescents
      and, in terms of health status, health behaviors and the experience of a serious
      disease were significant predictors of adolescent health risk behaviors. In this
      study, some demographic characteristics were predictors for health risk
      behaviors, in general, of adolescents. 

PMID- 24722617
TI  - Rhodiola rosea (SHR-5), Part 2: A standardized extract of Rhodiola rosea is shown
      to be effective in the treatment of mild to moderate depression.

PMID- 24722618
TI  - The association of income with health behavior change and disease monitoring
      among patients with chronic disease.
AB  - BACKGROUND: Management of chronic diseases requires patients to adhere to
      recommended health behavior change and complete tests for monitoring. While
      studies have shown an association between low income and lack of adherence, the
      reasons why people with low income may be less likely to adhere are unclear. We
      sought to determine the association between household income and receipt of
      health behavior change advice, adherence to advice, receipt of recommended
      monitoring tests, and self-reported reasons for non-adherence/non-receipt.
      METHODS: We conducted a population-weighted survey, with 1849 respondents with
      cardiovascular-related chronic diseases (heart disease, hypertension, diabetes,
      stroke) from Western Canada (n = 1849). We used log-binomial regression to
      examine the association between household income and the outcome variables of
      interest: receipt of advice for and adherence to health behavior change (sodium
      reduction, dietary improvement, increased physical activity, smoking cessation,
      weight loss), reasons for non-adherence, receipt of recommended monitoring tests
      (cholesterol, blood glucose, blood pressure), and reasons for non-receipt of
      tests. RESULTS: Behavior change advice was received equally by both low and high
      income respondents. Low income respondents were more likely than those with high
      income to not adhere to recommendations regarding smoking cessation (adjusted
      prevalence rate ratio (PRR): 1.55, 95%CI: 1.09-2.20), and more likely to not
      receive measurements of blood cholesterol (PRR: 1.72, 95%CI 1.24-2.40) or glucose
      (PRR: 1.80, 95%CI: 1.26-2.58). Those with low income were less likely to state
      that non-adherence/non-receipt was due to personal choice, and more likely to
      state that it was due to an extrinsic factor, such as cost or lack of
      accessibility. CONCLUSIONS: There are important income-related differences in the
      patterns of health behavior change and disease monitoring, as well as reasons for
      non-adherence or non-receipt. Among those with low income, adherence to health
      behavior change and monitoring may be improved by addressing modifiable barriers
      such as cost and access.

PMID- 24722619
TI  - Comorbidities and crash involvement among younger and older drivers.
AB  - Previous studies identified comorbidities as predictors of older driver
      performance and driving pattern, while the direct impact of comorbidities on road
      crash risk in elderly drivers is still unknown. The present study is a cross
      sectional aimed at investigating the association between levels of comorbidity
      and crash involvement in adult and elderly drivers. 327 drivers were stratified
      according to age range in two groups: elderly drivers (age >=70 years old,
      referred as older) and adult drivers (age <70 years old, referred as younger).
      Driving information was obtained through a driving questionnaire. Distance
      traveled was categorized into low, medium and high on the basis of kilometers
      driven in a year. CIRS-illness severity (IS) and CIRS-comorbidity indices (CI) in
      all populations were calculated. Older drivers had a significantly higher crash
      involvements rate (p = .045) compared with the younger group based on the number
      of licensed drivers. Dividing comorbidity indices into tertiles among all
      licensed subjects, the number of current drivers significantly decreased
      (p<.0001) with increasing level of comorbidity. The number of current drivers
      among older subjects significantly decreased with increasing comorbidity level (p
      = .026) while no difference among younger group was found (p = .462). Among
      younger drivers with increasing comorbidity level, the number of road accidents
      significantly increased (p = .048) and the logistic regression analysis showed
      that comorbidity level significantly associated with crash involvement
      independent of gender and driving exposure. Older subjects with high level of
      comorbidity are able to self-regulate driving while comorbidity burden represents
      a significant risk factor for crash involvements among younger drivers. 

PMID- 24722620
TI  - Clinical characteristics and immunogenetics of BCGosis/BCGitis in Chinese
      children: a 6 year follow-up study.
AB  - In this study, the clinical and immunogenetical features in a cohort of Chinese
      patients with BCGosis/BCGitis were investigated. For the patients with abnormal
      immunological functions, Sanger sequencing was used to identify the involved
      genes. There were 74 confirmed cases of BCGosis/BCGitis during 2007-2012.
      Classified by infected tissues and organs, no cases only had local infection, 39
      patients had a regional infection, 21 patients had a distant infection and 14
      patients had a disseminated infection. Thirty-two patients (43.2%) had definitive
      primary immunodeficiency diseases (PID) and chronic granulomatous disease (CGD)
      is the most common PID (n = 23, accounted for 71.9% of all PID patients). For CGD
      patients, based on the anti-tuberculosis treatment, administration of rhIFN-gamma
      resulted in better control of BCGosis/BCGitis. The results indicate that PIDs are
      associated with susceptibility to BCG disease. For children with BCGosis/BCGitis,
      immune function evaluation is necessary, and IFN-gamma treatment for
      BCGosis/BCGitis patients with CGD is effective. 

PMID- 24722621
TI  - Comparative planning of flattening-filter-free and flat beam IMRT for hypopharynx
      cancer as a function of beam and segment number.
AB  - Although highly conformal dose distributions can be achieved by IMRT planning,
      this often requires a large number of segments or beams, resulting in increased
      treatment times. While flattening-filter-free beams offer a higher dose rate,
      even more segments may be required to create homogeneous target coverage.
      Therefore, it is worthwhile to systematically investigate the dependence of plan
      quality on gantry angles and number of segments for flat vs. FFF beams in IMRT
      planning. For the practical example of hypopharynx cancer, we present a planning
      study of flat vs. FFF beams using three different configurations of gantry angles
      and different segment numbers. The two beams are very similar in physical
      properties, and are hence well-suited for comparative planning. Starting with a
      set of plans of equal quality for flat and FFF beams, we assess how far the
      number of segments can be reduced before the plan quality is markedly
      compromised, and compare monitor units and treatment times for the resulting
      plans. As long as a sufficiently large number of segments is permitted, all
      planning scenarios give good results, independently of gantry angles and flat or
      FFF beams. For smaller numbers of segments, plan quality decreases both for flat
      and FFF energies; this effect is stronger for fewer gantry angles and for FFF
      beams. For low segment numbers, FFF plans are generally worse than the
      corresponding flat beam plans, but they are less sensitive to a decrease in
      segment number if many gantry angles are used (18 beams); in this case the
      quality of flat and FFF plans remains comparable even for few segments. 

PMID- 24722622
TI  - Study of structural and dynamic characteristics of copper(II) amino acid
      complexes in solutions by combined EPR and NMR relaxation methods.
AB  - Structural features and dynamical behaviour of the copper(ii) bis-complexes with
      glycine, d-alanine, d-valine, l-serine, l-aspartic acid, l-glutamic acid, l
      lysine, l-proline, and sarcosine were studied by combined EPR and NMR relaxation
      methods. The cis and trans isomers were unambiguously assigned and characterized
      by EPR data. It was found that addition of a salt background has an influence on
      the cis-trans isomer equilibrium in favour of the formation of the cis isomer. By
      comparison of NMRD, DFT computations, and structural data it was shown that only
      one water molecule is coordinated in the axial position of these complexes. The
      increased exchange rates of this molecule found for Cu(l-Asp)2(2-), Cu(l-Glu)2(2
      ), Cu(l-LysH)2(2+), and Cu(l-Pro)2 were attributed to its pushing out by side
      chain groups of the ligands. By simulation of NMRD profiles an increase of
      lifetimes of the copper(ii) 2nd coordination sphere water molecules was revealed
      in the presence of additional carboxylic, alcoholic, or ammonium groups of the
      ligands, as well as the pyrrolidine ring of proline. The very short lifetimes of
      the 2nd coordination sphere water molecules (4-13 ps at 298 K) were explained in
      terms of the Frank-Wen structural model by the existence of cavities which draw
      in quickly enough water molecules from the 2nd coordination sphere. 

PMID- 24722624
TI  - Update in hematology and oncology: evidence published in 2013.

PMID- 24722623
TI  - Cooperative hydrolysis of aryl esters on functionalized membrane surfaces and in
      micellar solutions.
AB  - Catalytic hydrolysis of peptides, proteins, phosphates or carboxylate esters in
      nature is catalysed by enzymes, which are efficient, fast and selective. Most of
      the hydrolytic chemical catalysts published so far mimic the active site of
      enzymes and contain metal complexes and amino acid residues. Their synthesis can
      be laborious, while the hydrolytic activity is still limited compared to enzymes.
      We present an approach that uses fluid membranes of vesicles and micelles as a
      support for amphiphilic additives, which cooperatively cleave aryl ester bonds.
      The membrane anchored bis-Zn(II)-complex 1 is hydrolytically active and
      hydrolyses fluorescein diacetate (FDA) with a second order rate constant (k2) of
      0.9 M(-1) s(-1). The hydrolytic activity is modulated by co-embedded membrane
      additives, bearing common amino acid side chain functional groups. With this
      approach, the hydrolytic activity of the system is enhanced up to 16 fold in
      comparison with cyclen 1 (k2 = 14.7 M(-1) s(-1)). DOPC and DSPC lipids form at
      room temperature fluid or gel phase membranes, respectively. Omitting the lipid,
      micellar solutions were obtained with hydrolytic activity reaching k2 = 13.4 M(
      1) s(-1). It is shown that cooperative hydrolysis is favoured in fluid membranes
      and micelles, allowing the active moieties to arrange freely. The embedding and
      dynamic self-assembly of membrane active components in fluid membranes and
      micelles provide facile access to hydrolytically active soft interfaces.

PMID- 24722625
TI  - Diffusive fingering in a precipitation reaction driven by autocatalysis.
AB  - The interaction of an autocatalytic reaction with a fast precipitation reaction
      is shown to produce a permanent precipitate pattern where the major driving force
      is differential diffusion. The final structure emerges from the leading transient
      cellular front, the cusps of which evolve into precipitate free zones. The
      experimental observations are reproduced by a simple model calculation based on
      the empirical rate-law of the reaction. 

PMID- 24722626
TI  - Factors influencing coroners' verdicts: an analysis of verdicts given in 12
      coroners' districts to researcher-defined suicides in England in 2005.
AB  - BACKGROUND: To investigate the variation between coroners in the verdicts given
      to deaths thought by researchers to be probable suicides and analyse factors
      associated with the coroners' verdict. METHODS: Data were collected from 12
      English coroner districts on all deaths in 2005 given a suicide, open, accidental
      or narrative verdict where suicide was considered a possibility. The data were
      reviewed by three experienced suicide researchers. Regression models were used to
      investigate factors associated with the coroners' verdict. RESULTS: The
      researchers classified 593 deaths as suicide, of which 385 (65.4%) received a
      suicide verdict from the coroner. There was marked variation between coroner
      districts in the verdicts they gave. The suicide method was associated strongly
      with the coroners' verdict; deaths from poisoning and drowning were the least
      likely to be given suicide verdicts. The other factors strongly associated with a
      coroner's verdict of suicide were: whether a note was left, age over 60 years and
      being married or widowed compared with being single. CONCLUSION: Coroners vary
      considerably in the verdicts they give to individuals who probably died by
      suicide. This may compromise the usefulness of suicide statistics for assessing
      area differences in rates for public health surveillance.

PMID- 24722627
TI  - Electronic and phonon transport in Sb-doped
      Ti(0.1)Zr(0.9)Ni(1+x)Sn(0.975)Sb(0.025) nanocomposites.
AB  - The thermoelectric behavior of n-type Sb-doped half-Heusler (HH)-full-Heusler
      (FH) nanocomposites with general composition
      Ti(0.1)Zr(0.9)Ni(1+x)Sn(0.975)Sb(0.025) (x = 0, 0.02, 0.04, 0.1) was investigated
      in the temperature range from 300 to 775 K. Samples used for structural
      characterization and transport measurements were obtained through the solid-state
      reaction of high purity elements at 950  degrees C and densification of the
      resulting polycrystalline powders using a uniaxial hot press. X-ray diffraction
      study of the powder samples suggested the formation of single-phase HH alloys
      regardless of the Ni concentration (x value). However, high resolution
      transmission electron microscopy investigation revealed the presence of spherical
      nanoprecipitates with a broad size distribution coherently embedded in the HH
      matrix. The size range and dispersion of the precipitates depend on the
      concentration of Ni in the starting mixture. Well dispersed nanoprecipitates with
      size ranging from 5 nm to 50 nm are observed in the nanocomposite with x = 0.04,
      while severe agglomeration of large precipitates (>50 nm) is observed in samples
      with x = 0.1. Hall effect measurements of various samples indicate that the
      carrier concentration within the Sb-doped HH matrix remains nearly constant (~7 *
      10(20) cm(-3)) for samples with x = 0.02 and x = 0.04, whereas a significant
      increase of the carrier concentration to ~9 * 10(20) cm(-3) is observed for the
      sample with x = 0.1. Interestingly, only a marginal change in thermopower value
      is observed for various samples despite the large difference in the carrier
      density. In addition, the carrier mobility remains constant up to x = 0.04
      suggesting that the small nanoprecipitates in these samples do not disrupt
      electronic transport within the matrix. Remarkably, a large reduction in the
      total thermal conductivity is observed for all nanocomposites, indicating the
      effectiveness of the embedded nanoprecipitates in scattering phonons while
      enabling efficient electron transfer across the matrix/inclusion interfaces.

PMID- 24722628
TI  - Pernicious pathogens or expedient elements of inheritance: the significance of
      yeast prions.

PMID- 24722629
TI  - Impact of fire on active layer and permafrost microbial communities and
      metagenomes in an upland Alaskan boreal forest.
AB  - Permafrost soils are large reservoirs of potentially labile carbon (C).
      Understanding the dynamics of C release from these soils requires us to account
      for the impact of wildfires, which are increasing in frequency as the climate
      changes. Boreal wildfires contribute to global emission of greenhouse gases (GHG
      CO2, CH4 and N2O) and indirectly result in the thawing of near-surface
      permafrost. In this study, we aimed to define the impact of fire on soil
      microbial communities and metabolic potential for GHG fluxes in samples collected
      up to 1 m depth from an upland black spruce forest near Nome Creek, Alaska. We
      measured geochemistry, GHG fluxes, potential soil enzyme activities and microbial
      community structure via 16SrRNA gene and metagenome sequencing. We found that
      soil moisture, C content and the potential for respiration were reduced by fire,
      as were microbial community diversity and metabolic potential. There were shifts
      in dominance of several microbial community members, including a higher abundance
      of candidate phylum AD3 after fire. The metagenome data showed that fire had a
      pervasive impact on genes involved in carbohydrate metabolism, methanogenesis and
      the nitrogen cycle. Although fire resulted in an immediate release of CO2 from
      surface soils, our results suggest that the potential for emission of GHG was
      ultimately reduced at all soil depths over the longer term. Because of the size
      of the permafrost C reservoir, these results are crucial for understanding
      whether fire produces a positive or negative feedback loop contributing to the
      global C cycle. 

PMID- 24722630
TI  - Features of air masses associated with the deposition of Pseudomonas syringae and
      Botrytis cinerea by rain and snowfall.
AB  - Clarifying the role of precipitation in microbial dissemination is essential for
      elucidating the processes involved in disease emergence and spread. The ecology
      of Pseudomonas syringae and its presence throughout the water cycle makes it an
      excellent model to address this issue. In this study, 90 samples of freshly
      fallen rain and snow collected from 2005-2011 in France were analyzed for
      microbiological composition. The conditions favorable for dissemination of P.
      syringae by this precipitation were investigated by (i) estimating the physical
      properties and backward trajectories of the air masses associated with each
      precipitation event and by (ii) characterizing precipitation chemistry, and
      genetic and phenotypic structures of populations. A parallel study with the
      fungus Botrytis cinerea was also performed for comparison. Results showed that
      (i) the relationship of P. syringae to precipitation as a dissemination vector is
      not the same for snowfall and rainfall, whereas it is the same for B. cinerea and
      (ii) the occurrence of P. syringae in precipitation can be linked to electrical
      conductivity and pH of water, the trajectory of the air mass associated with the
      precipitation and certain physical conditions of the air mass (i.e. temperature,
      solar radiation exposure, distance traveled), whereas these predictions are
      different for B. cinerea. These results are pertinent to understanding microbial
      survival, emission sources and atmospheric processes and how they influence
      microbial dissemination. 

PMID- 24722631
TI  - Diverse sulfate-reducing bacteria of the Desulfosarcina/Desulfococcus clade are
      the key alkane degraders at marine seeps.
AB  - Biogeochemical and microbiological data indicate that the anaerobic oxidation of
      non-methane hydrocarbons by sulfate-reducing bacteria (SRB) has an important role
      in carbon and sulfur cycling at marine seeps. Yet, little is known about the
      bacterial hydrocarbon degraders active in situ. Here, we provide the link between
      previous biogeochemical measurements and the cultivation of degraders by direct
      identification of SRB responsible for butane and dodecane degradation in complex
      on-site microbiota. Two contrasting seep sediments from Mediterranean Amon mud
      volcano and Guaymas Basin (Gulf of California) were incubated with (13)C-labeled
      butane or dodecane under sulfate-reducing conditions and analyzed via
      complementary stable isotope probing (SIP) techniques. Using DNA- and rRNA-SIP,
      we identified four specialized clades of alkane oxidizers within
      Desulfobacteraceae to be distinctively active in oxidation of short- and long
      chain alkanes. All clades belong to the Desulfosarcina/Desulfococcus (DSS) clade,
      substantiating the crucial role of these bacteria in anaerobic hydrocarbon
      degradation at marine seeps. The identification of key enzymes of anaerobic
      alkane degradation, subsequent beta-oxidation and the reverse Wood-Ljungdahl
      pathway for complete substrate oxidation by protein-SIP further corroborated the
      importance of the DSS clade and indicated that biochemical pathways, analog to
      those discovered in the laboratory, are of great relevance for natural settings.
      The high diversity within identified subclades together with their capability to
      initiate alkane degradation and growth within days to weeks after substrate
      amendment suggest an overlooked potential of marine benthic microbiota to react
      to natural changes in seepage, as well as to massive hydrocarbon input, for
      example, as encountered during anthropogenic oil spills. 

PMID- 24722632
TI  - Gammaproteobacterial diazotrophs and nifH gene expression in surface waters of
      the South Pacific Ocean.
AB  - In addition to the cyanobacterial N2-fixers (diazotrophs), there is a high nifH
      gene diversity of non-cyanobacterial groups present in marine environments, yet
      quantitative information about these groups is scarce. N2 fixation potential
      (nifH gene expression), diversity and distributions of the uncultivated
      diazotroph phylotype gamma-24774A11, a putative gammaproteobacterium, were
      investigated in the western South Pacific Ocean. gamma-24774A11 gene copies
      correlated positively with diazotrophic cyanobacteria, temperature, dissolved
      organic carbon and ambient O2 saturation, and negatively with depth, chlorophyll
      a and nutrients, suggesting that carbon supply, access to light or inhibitory
      effects of DIN may control gamma-24774A11 abundances. Maximum nifH gene-copy
      abundance was 2 * 10(4) l(-1), two orders of magnitude less than that for
      diazotrophic cyanobacteria, while the median gamma-24774A11 abundance, 8 * 10(2)
      l(-1), was greater than that for the UCYN-A cyanobacteria, suggesting a more
      homogeneous distribution in surface waters. The abundance of nifH transcripts by
      gamma-24774A11 was greater during the night than during the day, and the
      transcripts generally ranged from 0-7%, but were up to 26% of all nifH
      transcripts at each station. The ubiquitous presence and low variability of gamma
      24774A11 abundances across tropical and subtropical oceans, combined with the
      consistent nifH expression reported in this study, suggest that gamma-24774A11
      could be one of the most important heterotrophic (or photoheterotrophic)
      diazotrophs and may need to be considered in future N budget estimates and
      models. 

PMID- 24722634
TI  - Colors cast long shadows on brain activity.

PMID- 24722633
TI  - Venlafaxine extended-release treatment of hoarding disorder.
AB  - Hoarding disorder, classified as a separate disorder in Diagnostic and
      Statistical Manual of Mental Disorders, 5th ed. (DSM-5), is a common, chronic,
      and potentially disabling syndrome that can be difficult to treat. Only one
      previous study prospectively measured response to pharmacotherapy in compulsive
      hoarders, finding that hoarders responded as well to paroxetine as did
      nonhoarding obsessive-compulsive disorder patients. However, paroxetine was not
      tolerated well in that study, and the overall response was moderate. Therefore,
      we conducted an open-label trial of venlafaxine extended-release for hoarding
      disorder. Twenty-four patients fulfilling the DSM-5 criteria for hoarding
      disorder were treated with venlafaxine extended-release for 12 weeks. All
      patients were free of psychotropic medications for at least 6 weeks before the
      study. No other psychotropic medications, cognitive-behavioral therapy,
      organizers, or cleaning crews were permitted during the study. To measure the
      severity of hoarding, the Saving Inventory-Revised (SI-R) and the UCLA Hoarding
      Severity Scale (UHSS) were administered before and after treatment. Twenty-three
      of the 24 patients completed treatment. Hoarding symptoms improved significantly,
      with a mean 36% decrease in UHSS scores and a mean 32% decrease in SI-R scores.
      Sixteen of the 23 completers (70%) were classified as responders to venlafaxine
      extended-release. These results suggest that venlafaxine extended-release may be
      effective for the treatment of hoarding disorder. 

PMID- 24722635
TI  - Implementing the optimal provision of ecosystem services.
AB  - Many ecosystem services are public goods whose provision depends on the spatial
      pattern of land use. The pattern of land use is often determined by the decisions
      of multiple private landowners. Increasing the provision of ecosystem services,
      though beneficial for society as a whole, may be costly to private landowners. A
      regulator interested in providing incentives to landowners for increased
      provision of ecosystem services often lacks complete information on landowners'
      costs. The combination of spatially dependent benefits and asymmetric cost
      information means that the optimal provision of ecosystem services cannot be
      achieved using standard regulatory or payment for ecosystem services approaches.
      Here we show that an auction that sets payments between landowners and the
      regulator for the increased value of ecosystem services with conservation
      provides incentives for landowners to truthfully reveal cost information, and
      allows the regulator to implement the optimal provision of ecosystem services,
      even in the case with spatially dependent benefits and asymmetric information. 

PMID- 24722636
TI  - RNA-RNA interactions and pre-mRNA mislocalization as drivers of group II intron
      loss from nuclear genomes.
AB  - Group II introns are commonly believed to be the progenitors of spliceosomal
      introns, but they are notably absent from nuclear genomes. Barriers to group II
      intron function in nuclear genomes therefore beg examination. A previous study
      showed that nuclear expression of a group II intron in yeast results in nonsense
      mediated decay and translational repression of mRNA, and that these roadblocks to
      expression are group II intron-specific. To determine the molecular basis for
      repression of gene expression, we investigated cellular dynamics of processed
      group II intron RNAs, from transcription to cellular localization. Our data show
      pre-mRNA mislocalization to the cytoplasm, where the RNAs are targeted to foci.
      Furthermore, tenacious mRNA-pre-mRNA interactions, based on intron-exon binding
      sequences, result in reduced abundance of spliced mRNAs. Nuclear retention of pre
      mRNA prevents this interaction and relieves these expression blocks. In addition
      to providing a mechanistic rationale for group II intron-specific repression, our
      data support the hypothesis that RNA silencing of the host gene contributed to
      expulsion of group II introns from nuclear genomes and drove the evolution of
      spliceosomal introns. 

PMID- 24722637
TI  - Sp8 regulates inner ear development.
AB  - A forward genetic screen of N-ethyl-N-nitrosourea mutagenized Xenopus tropicalis
      has identified an inner ear mutant named eclipse (ecl). Mutants developed
      enlarged otic vesicles and various defects of otoconia development; they also
      showed abnormal circular and inverted swimming patterns. Positional cloning
      identified specificity protein 8 (sp8), which was previously found to regulate
      limb and brain development. Two different loss-of-function approaches using
      transcription activator-like effector nucleases and morpholino oligonucleotides
      confirmed that the ecl mutant phenotype is caused by down-regulation of sp8.
      Depletion of sp8 resulted in otic dysmorphogenesis, such as uncompartmentalized
      and enlarged otic vesicles, epithelial dilation with abnormal sensory end organs.
      When overexpressed, sp8 was sufficient to induce ectopic otic vesicles possessing
      sensory hair cells, neurofilament innervation in a thickened sensory epithelium,
      and otoconia, all of which are found in the endogenous otic vesicle. We propose
      that sp8 is an important factor for initiation and elaboration of inner ear
      development. 

PMID- 24722638
TI  - Development of a highly sensitive loop-mediated isothermal amplification (LAMP)
      method for the detection of Loa loa.
AB  - The filarial parasite Loa loa, the causative agent of loiasis, is endemic in
      Central and Western Africa infecting 3-13 million people. L. loa has been
      associated with fatal encephalopathic reactions in high Loa-infected individuals
      receiving ivermectin during mass drug administration programs for the control of
      onchocerciasis and lymphatic filariasis. In endemic areas, the only diagnostic
      method routinely used is the microscopic examination of mid-day blood samples by
      thick blood film. Improved methods for detection of L. loa are needed in endemic
      regions with limited resources, where delayed diagnosis results in high
      mortality. We have investigated the use of a loop-mediated isothermal
      amplification (LAMP) assay to facilitate rapid, inexpensive, molecular diagnosis
      of loiasis. Primers for LAMP were designed from a species-specific repetitive DNA
      sequence from L. loa retrieved from GenBank. Genomic DNA of a L. loa adult worm
      was used to optimize the LAMP conditions using a thermocycler or a conventional
      heating block. Amplification of DNA in the LAMP mixture was visually inspected
      for turbidity as well as addition of fluorescent dye. LAMP specificity was
      evaluated using DNA from other parasites; sensitivity was evaluated using DNA
      from L. loa 10-fold serially diluted. Simulated human blood samples spiked with
      DNA from L. loa were also tested for sensitivity. Upon addition of fluorescent
      dye, all positive reactions turned green while the negative controls remained
      orange under ambient light. After electrophoresis on agarose gels, a ladder of
      multiple bands of different sizes could be observed in positive samples. The
      detection limit of the assay was found to be as little as 0.5 ag of L. loa
      genomic DNA when using a heating block. We have designed, for the first time, a
      highly sensitive LAMP assay for the detection of L. loa which is potentially
      adaptable for field diagnosis and disease surveillance in loiasis-endemic areas. 

PMID- 24722639
TI  - Pathobiological implications of mucin (MUC) expression in the outcome of small
      bowel cancer.
AB  - Mucins have been associated with survival in various cancer patients, but there
      have been no studies of mucins in small bowel carcinoma (SBC). In this study, we
      investigated the relationships between mucin expression and clinicopathologic
      factors in 60 SBC cases, in which expression profiles of MUC1, MUC2, MUC3, MUC4,
      MUC5AC, MUC6 and MUC16 in cancer and normal tissues were examined by
      immunohistochemistry. MUC1, MUC5AC and MUC16 expression was increased in SBC
      lesions compared to the normal epithelium, and expression of these mucins was
      related to clinicopathologic factors, as follows: MUC1 [tumor location (p =
      0.019), depth (p = 0.017) and curability (p = 0.007)], MUC5AC [tumor location (p
      = 0.063) and lymph node metastasis (p = 0.059)], and MUC16 [venous invasion (p =
      0.016) and curability (p = 0.016)]. Analysis of 58 cases with survival data
      revealed five factors associated with a poor prognosis: poorly-differentiated or
      neuroendocrine histological type (p<0.001), lymph node metastasis (p<0.001),
      lymphatic invasion (p = 0.026), venous invasion (p<0.001) and curative resection
      (p<0.001), in addition to expression of MUC1 (p = 0.042), MUC5AC (p = 0.007) and
      MUC16 (p<0.001). In subsequent multivariate analysis with curability as the
      covariate, lymph node metastasis, venous invasion, and MUC5AC and/or MUC16
      expression were significantly related to the prognosis. Multivariate analysis in
      curative cases (n = 45) showed that SBC with MUC5AC and/or MUC16 expression had a
      significantly independent high hazard risk after adjusting for the effects of
      venous invasion (hazard ratio: 5.6, 95% confidence interval: 1.8-17). In
      conclusion, the study shows that a MUC5AC-positive and/or MUC16-positive status
      is useful as a predictor of a poor outcome in patients with SBC. 

PMID- 24722640
TI  - HSV-2 increases TLR4-dependent phosphorylated IRFs and IFN-beta induction in
      cervical epithelial cells.
AB  - Our previous studies demonstrated that HSV-2 infection up-regulates TLR4
      expression and induces NF-kB activity, thereby facilitating innate immune
      response in human cervical epithelial cells. This process requires involvement of
      TLR4 adaptors, Mal and MyD88. In the current study, we found that HSV-2 infection
      increases levels of phosphoryalted IRF3 and IRF7, then regulating expression of
      type I IFN. As expected, these changes induced by HSV-2 infection depended upon
      TLR4. Knockdown of TRIF and/or TRAM by siRNAs indicated that TRIF/TRAM might be
      involved in expression of IFN-beta. Our results demonstrate for the first time
      that IRF3 and IRF7 are both involved in inducing TLR4-dependent IFN-beta
      expression in response to HSV-2 in its primary infected genital epithelial cells.
      Thus, TLR4-Mal/MyD88 and TLR4-TRIF/TRAM signaling may synergize and/or cooperate
      in innate immune response of cervical epithelial cells to HSV-2 infection.

PMID- 24722642
TI  - Thermal boundary conductance between Al films and GaN nanowires investigated with
      molecular dynamics.
AB  - GaN nanowires are being pursued for optoelectronic and high-power applications.
      In either use, increases in operating temperature reduce both performance and
      reliability making it imperative to minimize thermal resistances. Since
      interfaces significantly influence the thermal response of nanosystems, the
      thermal boundary resistance between GaN nanowires and metal contacts has major
      significance. In response, we have performed systematic molecular dynamics
      simulations to study the thermal boundary conductance between GaN nanowires and
      Al films as a function of nanowire dimensions, packing density, and the depth the
      nanowire is embedded into the metal contact. At low packing densities, the
      apparent Kapitza conductance between GaN nanowires and an aluminum film is shown
      to be larger than when contact is made between films of these same materials.
      This enhancement decreases toward the film-film limit, however, as the packing
      density increases. For densely packed nanowires, maximizing the Kapitza
      conductance can be achieved by embedding the nanowires into the films, as the
      conductance is found to be proportional to the total contact area. 

PMID- 24722641
TI  - Versatility of the Burkholderia cepacia complex for the biosynthesis of
      exopolysaccharides: a comparative structural investigation.
AB  - The Burkholderia cepacia Complex assembles at least eighteen closely related
      species that are ubiquitous in nature. Some isolates show beneficial potential
      for biocontrol, bioremediation and plant growth promotion. On the contrary, other
      strains are pathogens for plants and immunocompromised individuals, like cystic
      fibrosis patients. In these subjects, they can cause respiratory tract infections
      sometimes characterised by fatal outcome. Most of the Burkholderia cepacia
      Complex species are mucoid when grown on a mannitol rich medium and they also
      form biofilms, two related characteristics, since polysaccharides are important
      component of biofilm matrices. Moreover, polysaccharides contribute to bacterial
      survival in a hostile environment by inhibiting both neutrophils chemotaxis and
      antimicrobial peptides activity, and by scavenging reactive oxygen species. The
      ability of these microorganisms to produce exopolysaccharides with different
      structures is testified by numerous articles in the literature. However, little
      is known about the type of polysaccharides produced in biofilms and their
      relationship with those obtained in non-biofilm conditions. The aim of this study
      was to define the type of exopolysaccharides produced by nine species of the
      Burkholderia cepacia Complex. Two isolates were then selected to compare the
      polysaccharides produced on agar plates with those formed in biofilms developed
      on cellulose membranes. The investigation was conducted using NMR spectroscopy,
      high performance size exclusion chromatography, and gas chromatography coupled to
      mass spectrometry. The results showed that the Complex is capable of producing a
      variety of exopolysaccharides, most often in mixture, and that the most common
      exopolysaccharide is always cepacian. In addition, two novel polysaccharide
      structures were determined: one composed of mannose and rhamnose and another
      containing galactose and glucuronic acid. Comparison of exopolysaccharides
      obtained from cultures on agar plates with those extracted from biofilms on
      cellulose membranes showed important differences, thus suggesting that
      extrapolating data from non-biofilm conditions might not always be applicable. 

PMID- 24722643
TI  - Incidental prostate cancer at the time of cystectomy: the incidence and
      clinicopathological features in Chinese patients.
AB  - OBJECTIVES: To evaluate the incidence and the clinicopathological features of
      incidental prostate cancer detected in radical cystoprostatectomy (RCP) specimens
      in Chinese men and to estimate the oncological risk of prostate apex-sparing
      surgery for such patients. METHODS: The clinical data and pathological feature of
      504 patients who underwent RCP for bladder cancer from January 1999 to March 2013
      were retrospectively reviewed. Whole mount serial section of the RCP specimens
      were cut transversely at 3-4 mm intervals and examined in same pathological
      institution. RESULTS: Thirty-four out of 504 patients (6.8%) had incidental
      prostate cancer with a mean age of 70.3 years. 12 cases (35.2%) were diagnosed as
      significant disease. 4 cases were found to have apex involvement of
      adenocarcinoma of the prostate while in 5 cases the prostate stroma invasion by
      urothelial carcinoma were identified (one involved prostate apex). The mean
      follow-up time was 46.4+/-33.8 months. Biochemical recurrence occurred in 3
      patients but no prostate cancer-related death during the follow-up. There was no
      statistical significance in cancer specific survival between the clinically
      significant and insignificant cancer group. CONCLUSIONS: The prevalence of
      incidental prostate cancer in RCP specimens in Chinese patients was remarkably
      lower than in western people. Most of the incidental prostate cancer was
      clinically insignificant and patient's prognosis was mainly related to the
      bladder cancer. Sparing the prostate apex was potentially associated with a 1.0%
      risk of leaving significant cancer of the prostate or urothelial carcinoma.

PMID- 24722644
TI  - Relationship between tumor heterogeneity measured on FDG-PET/CT and pathological
      prognostic factors in invasive breast cancer.
AB  - BACKGROUND: There is currently little support to understand which pathological
      factors led to differences in tumor texture as measured from FDG PET/CT images.
      We studied whether tumor heterogeneity measured using texture analysis in FDG
      PET/CT images is correlated with pathological prognostic factors in invasive
      breast cancer. METHODS: Fifty-four patients with locally advanced breast cancer
      who had an initial FDG-PET/CT were retrospectively included. In addition to
      SUVmax, three robust textural indices extracted from 3D matrices: High-Gray-level
      Run Emphasis (HGRE), Entropy and Homogeneity were studied. Univariate and
      multivariate logistic regression was used to identify PET parameters associated
      with poor prognosis pathological factors: hormone receptor negativity, presence
      of HER-2 and triple negative phenotype. Receiver operating characteristic (ROC)
      curves and the (AUC) analysis, and reclassification measures, were performed in
      order to evaluate the performance of combining texture analysis and SUVmax for
      characterizing breast tumors. RESULTS: Tumor heterogeneity, measured with HGRE,
      was higher in negative estrogen receptor (p = 0.039) and negative progesterone
      receptor tumors (p = 0.036), and in Scarff-Bloom-Richardson grade 3 tumors (p =
      0.047). None of the PET indices could identify HER-2 positive tumors. Only SUVmax
      was positively correlated with Ki-67 (p<0.0004). Triple negative breast cancer
      (TNBC) exhibited higher SUVmax (Odd Ratio = 1.22, 95%CI [1.06-1.39],p = 0.004),
      lower Homogeneity (OR = 3.57[0.98-12.5],p = 0.05) and higher HGRE (OR = 8.06[1.88
      34.51],p = 0.005) than non-TNBC. Multivariate analysis showed that HGRE remained
      associated with TNBC (OR = 5.27[1.12-1.38],p = 0.03) after adjustment for SUVmax.
      Combining SUVmax and HGRE yielded in higher area under the ROC curves (AUC) than
      SUVmax for identifying TNBC: AUC =  0.83 and 0.77, respectively. Probability of
      correct classification also increased in 77% (10/13) of TNBC and 71% (29/41) of
      non-TNBC (p = 0.003), when combining SUVmax and HGRE. CONCLUSIONS: Tumor
      heterogeneity measured on FDG-PET/CT was higher in invasive breast cancer with
      poor prognosis pathological factors. Texture analysis might be used, in addition
      to SUVmax, as a new tool to assess invasive breast cancer aggressiveness.

PMID- 24722646
TI  - Cyclisation reactions of N-cinnamoyl-9-aminoanthracenes.
AB  - N-Cinnamoyl-9-aminoanthracenes cyclise with PPA or triflic acid to form novel 2
      azahexacyclo[10.6.6.0(1,5).0(6,11).0(13,18).0(19,24)]tetracosa
      6(11),7,9,13,15,17,19(24),20,22-nonaen-3-ones. In contrast, both N-cinnamoyl-N
      methyl-9-(2-aminomethyl)anthracene and N-cinnamoyl-9-(2-aminoethyl)anthracene
      undergo an intramolecular Diels-Alder cycloaddition. 

PMID- 24722645
TI  - Complex relationships between occupation, environment, DNA adducts, genetic
      polymorphisms and bladder cancer in a case-control study using a structural
      equation modeling.
AB  - DNA adducts are considered an integrate measure of carcinogen exposure and the
      initial step of carcinogenesis. Their levels in more accessible peripheral blood
      lymphocytes (PBLs) mirror that in the bladder tissue. In this study we explore
      whether the formation of PBL DNA adducts may be associated with bladder cancer
      (BC) risk, and how this relationship is modulated by genetic polymorphisms,
      environmental and occupational risk factors for BC. These complex
      interrelationships, including direct and indirect effects of each variable, were
      appraised using the structural equation modeling (SEM) analysis. Within the
      framework of a hospital-based case/control study, study population included 199
      BC cases and 213 non-cancer controls, all Caucasian males. Data were collected on
      lifetime smoking, coffee drinking, dietary habits and lifetime occupation, with
      particular reference to exposure to aromatic amines (AAs) and polycyclic aromatic
      hydrocarbons (PAHs). No indirect paths were found, disproving hypothesis on
      association between PBL DNA adducts and BC risk. DNA adducts were instead
      positively associated with occupational cumulative exposure to AAs (p = 0.028),
      whereas XRCC1 Arg 399 (p<0.006) was related with a decreased adduct levels, but
      with no impact on BC risk. Previous findings on increased BC risk by packyears
      (p<0.001), coffee (p<0.001), cumulative AAs exposure (p = 0.041) and MnSOD (p =
      0.009) and a decreased risk by MPO (p<0.008) were also confirmed by SEM analysis.
      Our results for the first time make evident an association between occupational
      cumulative exposure to AAs with DNA adducts and BC risk, strengthening the
      central role of AAs in bladder carcinogenesis. However the lack of an association
      between PBL DNA adducts and BC risk advises that these snapshot measurements are
      not representative of relevant exposures. This would envisage new scenarios for
      biomarker discovery and new challenges such as repeated measurements at different
      critical life stages. 

PMID- 24722647
TI  - Periviable birth: executive summary of a Joint Workshop by the Eunice Kennedy
      Shriver National Institute of Child Health and Human Development, Society for
      Maternal-Fetal Medicine, American Academy of Pediatrics, and American College of
      Obstetricians and Gynecologists.
AB  - This is an executive summary of a workshop on the management and counseling
      issues of women anticipated to deliver at a periviable gestation (broadly defined
      as 20 0/7 through 25 6/7 weeks of gestation), and the treatment options for the
      newborn. Upon review of the available literature, the workshop panel noted that
      the rates of neonatal survival and neurodevelopmental disabilities among the
      survivors vary greatly across the periviable gestations and are significantly
      influenced by the obstetric and neonatal management practices (for example,
      antenatal steroid, tocolytic agents and antibiotic administration; cesarean
      birth; and local protocols for perinatal care, neonatal resuscitation and
      intensive care support). These are, in turn, influenced by the variations in
      local and regional definitions of limits of viability. Because of the
      complexities in making difficult management decisions, obstetric and neonatal
      teams should confer prior to meeting with the family, when feasible. Family
      counseling should be coordinated with the goal of creating mutual trust, respect
      and understanding, and should incorporate evidence-based counseling methods.
      Since clinical circumstances can change rapidly with increasing gestational age,
      counseling should include discussion of the benefits and risks of various
      maternal and neonatal interventions at the time of counseling. There should be a
      plan for follow-up counseling as clinical circumstances evolve. The panel
      proposed a research agenda and recommended developing educational curricula on
      the care and counseling of families facing the birth of a periviable infant. 

PMID- 24722648
TI  - The utility of pain scores obtained during 'regular reassessment process' in
      premature infants in the NICU.
AB  - OBJECTIVE: To examine the association of pain assessment scores achieved through
      regular reassessment practice, as required by the Joint Commission (JC), with
      painful events and the use of analgesics in premature, ventilated infants. STUDY
      DESIGN: A cross-sectional study was performed in two tertiary level neonatal
      intensive care units. Pain was assessed at regular intervals at each center using
      validated multidimensional instruments in accordance with the JC standards.
      RESULT: Sample comprised 196 ventilated premature infant patient-days. Overall,
      2% of scores suggested the presence of pain, and 0.1% of pain scores were
      associated with analgesia. Ventilated infants who were exposed to multiple pain
      associated procedures in a day never demonstrated pain score elevations despite
      infrequent preemptive or continuous analgesic administration. CONCLUSION: Pain
      assessment scores achieved using regular reassessment processes were poorly
      correlated with exposure to pain-associated procedures or conditions. Low pain
      scores achieved through regular reassessment may not correlate to low pain
      exposure. Resources that are expended on regular reassessment processes may need
      to be reconsidered in light of the low yield for clinical alterations in care in
      this setting.

PMID- 24722650
TI  - Update in rheumatology: evidence published in 2013.

PMID- 24722649
TI  - The effects of caffeine on heart rate variability in newborns with apnea of
      prematurity.
AB  - OBJECTIVE: Apnea of prematurity is a common complication in premature newborns
      and caffeine is a widespread medication used to treat this complication. Caffeine
      may have adverse effects on the cardiovascular and central nervous system, yet
      its effects on the autonomic nervous system modulation of heart rate have not
      been studied in premature newborns, which was the objective of our study. STUDY
      DESIGN: We prospectively studied 21 premature newborns who were treated with
      caffeine. We analyzed heart rate variability by power spectral density and by
      dynamic nonlinear analyses methods. RESULT: There were no changes in heart rate,
      blood pressure or the autonomic nervous system tone following administration of
      caffeine, nor were the nonlinear dynamical properties of the system altered by
      caffeine. CONCLUSION: Caffeine does not have detrimental effects on heart rate
      variability, heart rate or blood pressure in conventional doses given to
      premature newborns.

PMID- 24722651
TI  - Density functional theory study of carbon dioxide electrochemical reduction on
      the Fe(100) surface.
AB  - Carbon dioxide electroreduction offers the possibility of producing hydrocarbon
      fuels using energy from renewable sources. Herein, we use density functional
      theory to analyze the feasibility of CO2 electroreduction on a Fe(100) surface.
      Experimentally, iron is nonselective for hydrocarbon formation. A simplistic
      analysis of low-coverage reaction intermediate energies for the paths to produce
      CH4 and CH3OH from CO2 suggests Fe(100) could be more active than Cu(111),
      currently the only metallic catalyst to show selectivity towards hydrocarbon
      formation. We consider a series of impediments to CO2 electroreduction on Fe(100)
      including O*/OH* (* denotes surface bound species) blockage of active surface
      sites; competitive adsorption effects of H*, CO* and C*; and iron carbide
      formation. Our results indicate that under CO2 electroreduction conditions,
      Fe(100) is predicted to be covered in C* or CO* species, blocking any C-H bond
      formation. Further, bulk Fe is predicted to be unstable relative to FeCx
      formation at potentials relevant to CO2 electroreduction conditions. 

PMID- 24722652
TI  - Paediatric gastroesophageal reflux clinical practice guidelines.

PMID- 24722655
TI  - Bony morphology of the knee and non-traumatic meniscal tears: is there a role for
      meniscal impingement?
AB  - OBJECTIVE: Meniscal tears are an important cause of morbidity. The aim of this
      study was to examine the relationship between non-traumatic meniscal tears and
      the intrinsic bony morphology of the knee. METHODS: A retrospective analysis of
      160 knee MRI scans in 150 patients was carried out who met the following
      criteria: (a) age between 20 and 45 years, (b) no history of knee trauma,
      surgery, infection, metabolic bone disease, and (c) no collateral or cruciate
      ligamentous injury. The medial tibial slope (MTS), lateral tibial slope (LTS),
      medial tibial plateau depth (MTPD), and medial and lateral femoral condylar
      offset ratios were calculated. The anterior horn, body, and posterior horn of the
      menisci were graded as 0 (no tear), 1 and 2 (degenerative changes), or 3
      (definitive tear). One-way ANOVA and linear regression was used for statistical
      analysis. RESULTS: In patients with grade 3 tears of the posterior horn of the
      medial meniscus, there was a significant association with shallower MTS (p <
      0.05), smaller medial femoral offset ratio (p < 0.05) and smaller lateral femoral
      offset ratio (p < 0.05). Patients with grade 3 tears of anterior horn of the
      lateral meniscus had a significant association with shallower LTS (p < 0.05). No
      significant association was seen between MTPD and meniscal tears. CONCLUSIONS:
      Our results suggest an association between bony morphology of the knee and non
      traumatic meniscal tears. Shallower MTS and LTS may result in impingement of
      posterior horn of medial meniscus and anterior horn of lateral meniscus,
      respectively. Future kinematic studies will be needed to help confirm our
      findings.

PMID- 24722656
TI  - Magnetic resonance imaging of abnormal shoulder pain following influenza
      vaccination.
AB  - The influenza vaccine is increasingly available to the general public and
      mandated by many employers in the United States. The prevalence of post
      vaccination complications is likely on the rise. Complications are well known to
      general clinicians, but are under-reported in the imaging literature. We present
      four cases of post-vaccination shoulder pain with magnetic resonance imaging
      (MRI) findings. An intrasubstance fluid-like signal in deep muscular and/or
      tendinous structures was the most common finding on MRI of these four cases.
      Focal bone marrow signal within the humeral head and inflammatory changes in the
      subacromial/subdeltoid bursa were also observed. The most likely reason for a
      humeral intraosseous edema-like signal was presumed injection of vaccine
      substance directly into osseous structures that might lead to focal osteitis. In
      the published literature, there is little emphasis on the imaging of local
      injection site complications accompanying influenza vaccination. We intended to
      increase familiarity of MRI findings in the setting of prolonged or severe
      clinical symptoms following influenza vaccination through the imaging findings of
      these four cases. 

PMID- 24722657
TI  - Diagnosis of osteosarcoma in a patient previously treated for Ewing sarcoma.
AB  - Primary malignant bone tumors, whether Ewing sarcoma or osteosarcoma, are a rare
      type of tumor. The sequential occurrence of two bone sarcomas, Ewing sarcoma and
      high-grade osteosarcoma, in the same patient at two different locations is an
      exceptionally rare phenomenon. We present the case of a 13-year-old girl who
      presented with a high-grade osteoblastic osteosarcoma of the distal femur, 7
      years after treatment for Ewing sarcoma of the left pelvis. She did not receive
      radiation therapy. Following the recent developing multidisciplinary therapy,
      long-term follow-up for monitoring latent treatment-related adverse effects may
      be necessary for survivors of primary malignant bone tumors. 

PMID- 24722662
TI  - Ultrahigh porosity in mesoporous MOFs: promises and limitations.
AB  - Mesoporous MOFs are currently record holders in terms of the specific surface
      area with values exceeding 7000 m(2) g(-1), a textural feature unattained by
      traditional porous solids such as zeolites, carbons and even by graphene. They
      are promising candidates for high pressure gas storage and also for conversion or
      separation of larger molecules, whose size exceeds the pore size of zeolites. The
      rational strategies for synthesis of mesoporous MOF are outlined and the
      unambiguous consistent assessment of the surface area of such ultrahighly porous
      materials, as well as present challenges in the exciting research field, of
      mesoporous MOFs are discussed. The crystallinity, dynamic properties, functional
      groups, and wide range tunability render these materials as exceptional solids,
      but for the implementation in functional devices and even in industrial processes
      several aspects and effective characteristics (such as volumetric storage
      capacities, recyclability, mechanical and chemical stability, activation) should
      be addressed. 

PMID- 24722658
TI  - Synthesis and structure of a ferric complex of 2,6-di(1H-pyrazol-3-yl)pyridine
      and its excellent performance in the redox-controlled living ring-opening
      polymerization of epsilon-caprolactone.
AB  - The reaction of FeCl3 with a pincer ligand, 2,6-di(1H-pyrazol-3-yl)pyridine
      (bppyH2), produced a mononuclear Fe(III) complex [Fe(bppyH2)Cl3] (1), which could
      be reduced to the corresponding Fe(II) dichloride complex [Fe(bppyH2)Cl2] (2) by
      suitable reducing agents such as Cp2Co or Fe powder. 1 and 2 exhibited a
      reversible transformation from each other with appropriate redox reagents. 1
      could be utilized as a pre-catalyst to initiate the ring-opening polymerization
      of epsilon-caprolactone in the presence of alcohol but did not work. The
      1/alcohol system displayed characteristics of a well-controlled polymerization
      with the resulting poly(epsilon-caprolactone) having low molecular weight
      distributions, a linear tendency of molecular weight evolution with conversion,
      and polymer growth observed for the sequential additions of epsilon-caprolactone
      monomer to the polymerization reaction. The polymerization was completely turned
      off by the in situ reduction of the catalytic Fe center via Cp2Co and then turned
      back upon the addition of [Cp2Fe]PF6. The rate of polymerization was modified by
      switching in situ between the Fe(III) and Fe(II) species.

PMID- 24722663
TI  - Human intracranial high frequency oscillations (HFOs) detected by automatic time
      frequency analysis.
AB  - OBJECTIVES: High frequency oscillations (HFOs) have been proposed as a new
      biomarker for epileptogenic tissue. The exact characteristics of clinically
      relevant HFOs and their detection are still to be defined. METHODS: We propose a
      new method for HFO detection, which we have applied to six patient iEEGs. In a
      first stage, events of interest (EoIs) in the iEEG were defined by thresholds of
      energy and duration. To recognize HFOs among the EoIs, in a second stage the iEEG
      was Stockwell-transformed into the time-frequency domain, and the instantaneous
      power spectrum was parameterized. The parameters were optimized for HFO detection
      in patient 1 and tested in patients 2-5. Channels were ranked by HFO rate and
      those with rate above half maximum constituted the HFO area. The seizure onset
      zone (SOZ) served as gold standard. RESULTS: The detector distinguished HFOs from
      artifacts and other EEG activity such as interictal epileptiform spikes.
      Computation took few minutes. We found HFOs with relevant power at frequencies
      also below the 80-500 Hz band, which is conventionally associated with HFOs. The
      HFO area overlapped with the SOZ with good specificity > 90% for five patients
      and one patient was re-operated. The performance of the detector was compared to
      two well-known detectors. CONCLUSIONS: Compared to methods detecting energy
      changes in filtered signals, our second stage - analysis in the time-frequency
      domain - discards spurious detections caused by artifacts or sharp epileptic
      activity and improves the detection of HFOs. The fast computation and reasonable
      accuracy hold promise for the diagnostic value of the detector.

PMID- 24722664
TI  - The effect of diphenhydramine on sleep in pediatric burn patients: a secondary
      analysis.
AB  - Adequate sleep is essential for maintaining homeostasis, especially when
      recovering from an illness; however, studies have shown that sleep disruption and
      sleep deprivation are common in intensive care unit patients, including children
      who have sustained burn injury. The purpose of this study was to evaluate the
      effect of diphenhydramine (DPH) on sleep in pediatric intensive care unit burn
      patients using Myra Levine's Conservation Model as the organizing framework. For
      this study, secondary analysis of polysomnography data and retrospective chart
      review were used. Twelve DPH patients were pair matched in terms of morphine,
      midazolam, and methadone with 12 non-DPH patients. The data were analyzed using
      paired t-tests for each dependent variable and chi analysis was used for
      frequency determinations. There was no difference in demographics between the two
      groups. DPH patients took 4.3 +/- 1.6 minutes to fall asleep whereas non-DPH
      patients took 15.8 +/- 1.6 minutes to achieve sleep onset (P = .06). Patients
      receiving DPH achieved 297.6 +/- 29.9 minutes of total sleep time whereas those
      not receiving DPH achieved only 209.2 +/- 29.9 minutes (P < .05). There was
      minimal difference in the mean percentage of sleep time in stages 3 and 4 between
      the two groups. The DPH group did have 50% more rapid eye movement sleep time
      compared with the non-DPH group. Even though DPH did not result in a statistical
      improvement in sleep quality, sleep quantity was increased in this study. More
      research is needed to find an effective sleep intervention in pediatric burn
      patients. 

PMID- 24722665
TI  - Enteral nutrition: what the dietitian prescribes is not what the burn patient
      gets!
AB  - Enteral nutrition (EN) is commonly interrupted in burn patients for many reasons,
      which leads to discrepancies between prescribed and actual EN delivery. The
      magnitude and origin of these discrepancies have never been well documented among
      burn patients. The purpose of this study was to examine differences between
      prescribed and actual EN delivery and to identify the specific causes of EN
      interruption and to quantify these. Retrospective review of patients treated
      between June 6, 2009 and June 6, 2012 at an adult regional American Burn
      Association-verified burn center who had >=10% TBSA burns and who were prescribed
      EN for at least 24 hours. On postburn days (PBD) 0 to 14 the daily volume of EN
      prescribed by the dietitian was compared with the actual volume received by the
      patient. The cause and duration of interruptions to EN delivery were recorded. A
      total of 90 subjects, [mean (+/- SD) age 47 +/- 18 years, 32% female, median
      %TBSA burn size 28, median %TBSA full-thickness burn size 11, and a 54% incidence
      of inhalation injury], were studied. EN was initiated at a median of 9.5 hours
      after burn center admission. Received calories were significantly less than
      prescribed calories on every study day. The median daily caloric deficit ranged
      between 172 and 930 kcal. The median percent of prescribed calories received each
      day ranged from 19% on PBD 0 to 91% on PBD 14. The mean (+/- SD) total duration
      of EN interruption was 8.9 +/- 3.0 hours per day. Gradually increasing the feed
      rate to reach the prescribed EN goal rate ("ramping-in") was the most common
      cause of a discrepancy between prescribed and actual EN delivery, accounting for
      35% of total discrepancy time. Interruptions for surgery accounted for 24% of
      total discrepancy time. Other causes of discrepancies were physician- or nurse
      directed interruptions (16% of time), planned extubation (7%), feed intolerance
      (11%), tube malfunction (2%), bedside procedures (2%), and dressing changes
      (3%).Enterally fed burn patients received significantly less nutrition than
      prescribed. Some of the causes for discrepancies between prescribed and received
      EN are unavoidable, but many are not, suggesting the need for careful review and
      possible alteration of existing EN practices. 

PMID- 24722666
TI  - Chemical derivatives of a small molecule deubiquitinase inhibitor have antiviral
      activity against several RNA viruses.
AB  - Most antiviral treatment options target the invading pathogen and unavoidably
      encounter loss of efficacy as the pathogen mutates to overcome replication
      restrictions. A good strategy for circumventing drug resistance, or for pathogens
      without treatment options, is to target host cell proteins that are utilized by
      viruses during infection. The small molecule WP1130 is a selective deubiquitinase
      inhibitor shown previously to successfully reduce replication of noroviruses and
      some other RNA viruses. In this study, we screened a library of 31 small molecule
      derivatives of WP1130 to identify compounds that retained the broad-spectrum
      antiviral activity of the parent compound in vitro but exhibited improved drug
      like properties, particularly increased aqueous solubility. Seventeen compounds
      significantly reduced murine norovirus infection in murine macrophage RAW 264.7
      cells, with four causing decreases in viral titers that were similar or slightly
      better than WP1130 (1.9 to 2.6 log scale). Antiviral activity was observed
      following pre-treatment and up to 1 hour postinfection in RAW 264.7 cells as well
      as in primary bone marrow-derived macrophages. Treatment of the human norovirus
      replicon system cell line with the same four compounds also decreased levels of
      Norwalk virus RNA. No significant cytotoxicity was observed at the working
      concentration of 5 uM for all compounds tested. In addition, the WP1130
      derivatives maintained their broad-spectrum antiviral activity against other RNA
      viruses, Sindbis virus, LaCrosse virus, encephalomyocarditis virus, and Tulane
      virus. Thus, altering structural characteristics of WP1130 can maintain effective
      broad-spectrum antiviral activity while increasing aqueous solubility. 

PMID- 24722667
TI  - Molecular and functional characterization of cDNAs putatively encoding
      carboxylesterases from the migratory locust, Locusta migratoria.
AB  - Carboxylesterases (CarEs) belong to a superfamily of metabolic enzymes encoded by
      a number of genes and are widely distributed in microbes, plants and animals
      including insects. These enzymes play important roles in detoxification of
      insecticides and other xenobiotics, degradation of pheromones, regulation of
      neurodevelopment, and control of animal development. In this study, we
      characterized a total of 39 full-length cDNAs putatively encoding different CarEs
      from the migratory locust, Locusta migratoria, one of the most severe insect
      pests in many regions of the world, and evaluated the role of four CarE genes in
      insecticide detoxification. Our phylogenetic analysis grouped the 39 CarEs into
      five different clades including 20 CarEs in clade A, 3 in D, 13 in E, 1 in F and
      2 in I. Four CarE genes (LmCesA3, LmCesA20, LmCesD1, LmCesE1), representing three
      different clades (A, D and E), were selected for further analyses. The
      transcripts of the four genes were detectable in all the developmental stages and
      tissues examined. LmCesA3 and LmCesE1 were mainly expressed in the fat bodies and
      Malpighian tubules, whereas LmCesA20 and LmCesD1 were predominately expressed in
      the muscles and hemolymph, respectively. The injection of double-stranded RNA
      (dsRNA) synthesized from each of the four CarE genes followed by the bioassay
      with each of four insecticides (chlorpyrifos, malathion, carbaryl and
      deltamethrin) increased the nymphal mortalities by 37.2 and 28.4% in response to
      malathion after LmCesA20 and LmCesE1 were silenced, respectively. Thus, we
      proposed that both LmCesA20 and LmCesE1 played an important role in
      detoxification of malathion in the locust. These results are expected to help
      researchers reveal the characteristics of diverse CarEs and assess the risk of
      insecticide resistance conferred by CarEs in the locust and other insect species.

PMID- 24722668
TI  - Host-to-pathogen gene transfer facilitated infection of insects by a pathogenic
      fungus.
AB  - Metarhizium robertsii is a plant root colonizing fungus that is also an insect
      pathogen. Its entomopathogenicity is a characteristic that was acquired during
      evolution from a plant endophyte ancestor. This transition provides a novel
      perspective on how new functional mechanisms important for host switching and
      virulence have evolved. From a random T-DNA insertion library, we obtained a
      pathogenicity defective mutant that resulted from the disruption of a sterol
      carrier gene (Mr-npc2a). Phylogenetic analysis revealed that Metarhizium acquired
      Mr-npc2a from an insect by horizontal gene transfer (HGT). Mr-NPC2a binds to
      cholesterol, an animal sterol, rather than the fungal sterol ergosterol,
      indicating it retains the specificity of insect NPC2 proteins. Mr-NPC2a is an
      intracellular protein and is exclusively expressed in the hemolymph of living
      insects. The disruption of Mr-npc2a reduced the amount of sterol in cell
      membranes of the yeast-like hyphal bodies that facilitate dispersal in the host
      body. These were consequently more susceptible to insect immune responses than
      the wild type. Transgenic expression of Mr-NPC2a increased the virulence of
      Beauveria bassiana, an endophytic insect-pathogenic fungus that lacks a Mr-NPC2a
      homolog. 

PMID- 24722670
TI  - Conformational stability as a design target to control protein aggregation.
AB  - Non-native protein aggregation is a prevalent problem occurring in many
      biotechnological manufacturing processes and can compromise the biological
      activity of the target molecule or induce an undesired immune response.
      Additionally, some non-native aggregation mechanisms lead to amyloid fibril
      formation, which can be associated with debilitating diseases. For natively
      folded proteins, partial or complete unfolding is often required to populate
      aggregation-prone conformational states, and therefore one proposed strategy to
      mitigate aggregation is to increase the free energy for unfolding (DeltaGunf)
      prior to aggregation. A computational design approach was tested using human
      gammaD crystallin (gammaD-crys) as a model multi-domain protein. Two mutational
      strategies were tested for their ability to reduce/increase aggregation rates by
      increasing/decreasing DeltaGunf: stabilizing the less stable domain and
      stabilizing the domain-domain interface. The computational protein design
      algorithm, RosettaDesign, was implemented to identify point variants. The results
      showed that although the predicted free energies were only weakly correlated with
      the experimental DeltaGunf values, increased/decreased aggregation rates for
      gammaD-crys correlated reasonably well with decreases/increases in experimental
      DeltaGunf, illustrating improved conformational stability as a possible design
      target to mitigate aggregation. However, the results also illustrate that
      conformational stability is not the sole design factor controlling aggregation
      rates of natively folded proteins. 

PMID- 24722669
TI  - A systematic comparison of the anti-tumoural activity and toxicity of the three
      Adv-TKs.
AB  - Adenovirus 5 vectors, known respectively as, the first generation, second
      generation and oncolytic adenovirus, have been studied extensively in preclinical
      and clinical trials. However, hitherto few systemic evaluations of the efficacy
      and toxicity of these adenoviral vectors that have reflected the vertical history
      of adenovirus based cancer gene therapy strategies have been undertaken. This
      study has chosen Adv-TK, the well-established adjuvant treatment in cancer, and
      compared its efficacy and safety with those of the two newly synthesized
      oncolytic adenovirus vectors encoding the HSV-TK gene, namely M7 and M8. The
      results obtained showed that systemic administration of 1*10(8) pfu M7 had an
      anti-tumour efficacy similar to that of 3*10(10) pfu Adv-TK whilst M8 performed
      even better. Furthermore, compared to Adv-TK, M7 and M8 reduced the incidence of
      metastases and substantially prolonged the survival time of the mice xenografted
      with human orthotopic gastric carcinomas with disseminated metastasis. Even more
      exciting, however, were the similar toxic and immune safety results obtained from
      the administration of high doses of M7 or M8 in comparison with Adv-TK in
      immunocompetent and permissive syrian hamster. The data here exhibit a
      comprehensive display of the efficacy and safety of the three mutants and provide
      evidence for the future preclinical use of the M7 and M8 viruses.

PMID- 24722671
TI  - A genetic analysis of the functional interactions within Mycobacterium
      tuberculosis single-stranded DNA binding protein.
AB  - Single-stranded DNA binding proteins (SSBs) are vital in all organisms. SSBs of
      Escherichia coli (EcoSSB) and Mycobacterium tuberculosis (MtuSSB) are
      homotetrameric. The N-terminal domains (NTD) of these SSBs (responsible for their
      tetramerization and DNA binding) are structurally well defined. However, their C
      terminal domains (CTD) possess undefined structures. EcoSSB NTD consists of beta1
      beta1'-beta2-beta3-alpha-beta4-beta451-beta452-beta5 secondary structure
      elements. MtuSSB NTD includes an additional beta-strand (beta6) forming a novel
      hook-like structure. Recently, we observed that MtuSSB complemented an E. coli
      Deltassb strain. However, a chimeric SSB (mbeta4-beta5), wherein only the
      terminal part of NTD (beta4-beta5 region possessing L45 loop) of EcoSSB was
      substituted with that from MtuSSB, failed to function in E. coli in spite of its
      normal DNA binding and oligomerization properties. Here, we designed new chimeras
      by transplanting selected regions of MtuSSB into EcoSSB to understand the
      functional significance of the various secondary structure elements within SSB.
      All chimeric SSBs formed homotetramers and showed normal DNA binding. The mbeta4
      beta6 construct obtained by substitution of the region downstream of beta5 in
      mbeta4-beta5 SSB with the corresponding region (beta6) of MtuSSB complemented the
      E. coli strain indicating a functional interaction between the L45 loop and the
      beta6 strand of MtuSSB.

PMID- 24722672
TI  - Studies on the stereochemical assignment of 3-acylidene 2-oxindoles.
AB  - The designation of E/Z-geometrical isomers in 3-acylidene 2-oxindoles by NMR
      spectroscopy can lead to erroneous assignment of alkene stereochemistry because
      of the narrow chemical shift range observed over a large series of analogues. In
      contrast, UV-Vis spectroscopy offers a convenient and more reliable method for
      alkene stereochemical assignment. A combination of X-ray crystallography and
      theoretical studies shows that the observed differences in UV-Vis spectroscopic
      behaviour relate to the twisted conformation of the Z-isomers that provides
      reduced conjugation and weaker hypsochromic (blue-shifted) absorbances relative
      to those of the E-isomers. 

PMID- 24722673
TI  - Wolbachia infect ovaries in the course of their maturation: last minute
      passengers and priority travellers?
AB  - Wolbachia are widespread endosymbiotic bacteria of arthropods and nematodes.
      Studies on such models suggest that Wolbachia's remarkable aptitude to infect
      offspring may rely on a re-infection of ovaries from somatic tissues instead of
      direct cellular segregation between oogonia and oocytes. In the terrestrial
      isopod Armadillidium vulgare, Wolbachia are vertically transmitted to the host
      offspring, even though ovary cells are cyclically renewed. Using Fluorescence in
      situ hybridization (FISH), we showed that the proportion of infected oocytes
      increased in the course of ovary and oocyte maturation, starting with 31.5% of
      infected oocytes only. At the end of ovary maturation, this proportion reached
      87.6% for the most mature oocytes, which is close to the known transmission rate
      to offspring. This enrichment can be explained by a secondary acquisition of the
      bacteria by oocytes (Wolbachia can be seen as last minute passengers) and/or by a
      preferential selection of oocytes infected with Wolbachia (as priority
      travellers). 

PMID- 24722675
TI  - Update in Women's Health: evidence published in 2013.

PMID- 24722674
TI  - Color and polarization vision in foraging Papilio.
AB  - This paper gives an overview of behavioral studies on the color and polarization
      vision of the Japanese yellow swallowtail butterfly, Papilio xuthus. We focus on
      indoor experiments on foraging individuals. Butterflies trained to visit a disk
      of certain color correctly select that color among various other colors and/or
      shades of gray. Correct selection persists under colored illumination, but is
      systematically shifted by background colors, indicating color constancy and
      simultaneous color contrast. While their eyes contain six classes of spectral
      receptors, their wavelength discrimination performance indicates that their color
      vision is tetrachromatic. P. xuthus innately prefers brighter targets, but can be
      trained to select dimmer ones under certain conditions. Butterflies trained to a
      dark red stimulus select an orange disk presented on a bright gray background
      over one on dark gray. The former probably appears darker to them, indicating
      brightness contrast. P. xuthus has a strong innate preference for vertically
      polarized light, but the selection of polarized light changes depending on the
      intensity of simultaneously presented unpolarized light. Discrimination of
      polarization also depends on background intensity. Similarities between
      brightness and polarization vision suggest that P. xuthus perceive polarization
      angle as brightness, such that vertical polarization appears brighter than
      horizontal polarization. 

PMID- 24722676
TI  - Double figure-of-eight reconstruction technique for chronic anterior
      sternoclavicular joint dislocation.
AB  - Sternoclavicular joint dislocations account for <5 % of all dislocations of the
      shoulder girdle. Whereas most cases of anterior dislocation do not experience
      symptoms, some patients with anterior instability remain symptomatic and require
      reconstructive surgery to stabilize the sternoclavicular joint. We present the
      case of a 57-year-old male diagnosed with sternoclavicular joint anterior
      dislocation and unusual swallowing difficulty while bending the neck forward. The
      patient was treated using a new and effective surgical technique of
      sternoclavicular joint reconstruction named "double figure-of-eight" using the
      ipsilateral gracilis tendon. Surgical outcome was successful, based on the
      Rockwood SC joint rating scale, and the patient maintained excellent stability
      even after 2 years. This new surgical technique offers superior stability,
      without harvest site morbidity, to patients with rare, severe, and chronic
      sternoclavicular joint dislocation. Level of evidence IV.

PMID- 24722677
TI  - Equid herpesvirus type 4 uses a restricted set of equine major histocompatibility
      complex class I proteins as entry receptors.
AB  - Equid herpesvirus type 1 (EHV-1) was shown to use an unusual receptor for
      cellular entry - MHC-I molecules. Here, we demonstrated that the closely related
      EHV, EHV-4, also uses this strategy for cellular invasion, both in equine cells
      in culture and in the heterologous, non-permissive murine mastocytoma cell line
      (P815) after stable transfection with horse MHC-I genes. Using a panel of P815
      cell lines transfected with individual horse MHC-I genes, we provided support for
      the hypothesis that EHV-1 and EHV-4 target classical polymorphic MHC-I molecules
      as viral entry receptors. All known equine MHC-I molecules from the two principal
      classical polymorphic loci specify alanine at position 173 (A173), whilst other
      MHC-I loci encoded different amino acids at this position and did not permit
      viral entry. Site-directed mutagenesis of position 173 diminished or enhanced
      viral entry, depending upon the initial amino acid. However, there were other, as
      yet undefined, constraints to this process: MHC-I genes from two non-classical
      loci carried A173 but did not enable viral entry in P815 transfectants. Our study
      suggested that the capacity to bind MHC-I molecules arose in the common ancestor
      of EHV-1 and EHV-4. The widespread occurrence of A173 in classical polymorphic
      horse MHC-I molecules indicated that horses of most MHC haplotypes should be
      susceptible to infection via this entry portal. 

PMID- 24722678
TI  - Differential restriction patterns of mRNA decay factor AUF1 during picornavirus
      infections.
AB  - During infection by picornaviruses, the cellular environment is modified to
      favour virus replication. This includes the modification of specific host
      proteins, including the recently discovered viral proteinase cleavage of mRNA
      decay factor AU-rich binding factor 1 (AUF1). This cellular RNA-binding protein
      was shown previously to act as a restriction factor during poliovirus, rhinovirus
      and coxsackievirus infection. During infection by these viruses, AUF1 relocalizes
      to the cytoplasm and is cleaved by the viral 3C/3CD proteinase. In this study, we
      demonstrated that replication of encephalomyocarditis virus (EMCV), a
      picornavirus belonging to the genus Cardiovirus, is AUF1 independent. During EMCV
      infection, AUF1 relocalized to the cytoplasm; however, unlike what is seen during
      enterovirus infections, AUF1 was not cleaved to detectable levels, even at late
      times after infection. This suggests that AUF1 does not act broadly as an
      inhibitor of picornavirus infections but may instead act as a selective
      restriction factor targeting members of the genus Enterovirus. 

PMID- 24722679
TI  - Molecular and cellular mechanisms underlying potyvirus infection.
AB  - Potyviruses represent one of the most economically important and widely
      distributed groups of plant viruses. Despite considerable progress towards
      understanding the cellular and molecular basis of their pathogenicity, many
      questions remain about the mechanisms by which potyviruses suppress host defences
      and create an optimal intracellular environment for viral translation,
      replication, assembly and spread. The review focuses on the multifunctional roles
      of potyviral proteins and their interplay with various host factors in different
      compartments of the infected cell. We place special emphasis on the recently
      discovered and currently putative mechanisms by which potyviruses subvert the
      normal functions of different cellular organelles in order to establish an
      efficient and productive infection. 

PMID- 24722681
TI  - Genome sequence of a crustacean iridovirus, IIV31, isolated from the pill bug,
      Armadillidium vulgare.
AB  - Members of the family Iridoviridae are animal viruses that infect only
      invertebrates and poikilothermic vertebrates. The invertebrate iridovirus 31
      (IIV31) was originally isolated from adult pill bugs, Armadillidium vulgare
      (class Crustacea, order Isopoda, suborder Oniscidea), found in southern
      California on the campus of the University of California, Riverside, USA. IIV31
      virions are icosahedral, have a diameter of about 135 nm, and contain a dsDNA
      genome 220.222 kbp in length, with 35.09 mol % G+C content and 203 ORFs. Here, we
      describe the complete genome sequence of this virus and its annotation. This is
      the eighth genome sequence of an IIV reported. 

PMID- 24722682
TI  - Polysaccharide isolated from Parmelia tinctorum ameliorates ionizing irradiation
      induced damage in mice.
AB  - In this study, WPT-A, a type of water-soluble homogeneous lichen polysaccharide,
      was isolated and purified from Parmelia tinctorum. We investigated whether WPT-A
      has radioprotective effects when administered before total-body irradiation
      (TBI). Mice were treated with WPT-A via intraperitoneal injection (i.p.) once per
      day for three consecutive days prior to 7, 7.5, 8.5, 10 or 10.5-Gy TBI. Our
      results indicated that the survival rate was enhanced at a range of levels of
      TBI. The calculated dose reduction factor (DRF) was 1.2. White blood cell (WBC)
      counts, spleen colony forming units (CFU-S) and bone marrow nucleated cell (BMNC)
      counts were used to investigate the radioprotective effects of WPT-A on the
      hematopoietic system. The treatment groups received WPT-A at 20, 50 and 80 mg/kg
      b.w. doses before 6.5-Gy TBI and showed significantly higher BMNC and WBC counts
      compared with the radiation-only group. The groups administered 50 and 80 mg/kg
      b.w. WPT-A showed a significant increase in CFU-S compared with the radiation
      only group. We also carried out a single cell gel electrophoresis assay to
      explore the radioprotective effects of WPT-A on DNA damage. The results from
      single-cell gel electrophoresis of peripheral blood leukocytes showed that WPT-A
      attenuated radiation-induced DNA damage. These results indicate a potential use
      for WPT-A as a radioprotector.

PMID- 24722683
TI  - How air influences radiation dose deposition in multiwell culture plates: a Monte
      Carlo simulation of radiation geometry.
AB  - Radiation of experimental culture cells on plates with various wells can cause a
      risk of underdosage as a result of the existence of multiple air-water
      interfaces. The objective of our study was to quantify this error in culture
      plates with multiple wells. Radiation conditions were simulated with the GAMOS
      code, based on the GEANT4 code, and this was compared with a simulation performed
      with PENELOPE and measured data. We observed a slight underdosage of ~ 4% on the
      most superficial half of the culture medium. We believe that this underdosage
      does not have a significant effect on the dose received by culture cells
      deposited in a monolayer and adhered to the base of the wells.

PMID- 24722684
TI  - The chemistry and applications of multimetallic salen complexes.
AB  - Multimetallic salen complexes have found utility in a number of fields from
      materials chemistry to catalysis. The objective of this perspective is to discuss
      the development of new synthetic strategies to multitopic ligands based on Schiff
      base chemistry, and the isolation and study of the resulting metal complexes.
      Developments in catalysis, magnetism, electronic structure, and small-molecule
      sensing are presented demonstrating the considerable potential of these ligand
      constructs in facilitating new chemistry. 

PMID- 24722680
TI  - Molecular characterization of avian influenza H5N1 virus in Egypt and the
      emergence of a novel endemic subclade.
AB  - Clade 2.2 highly pathogenic H5N1 viruses have been in continuous circulation in
      Egyptian poultry since 2006. Their persistence caused significant genetic drift
      that led to the reclassification of these viruses into subclades 2.2.1 and
      2.2.1.1. Here, we conducted full-genome sequence and phylogenetic analyses of 45
      H5N1 isolated during 2006-2013 through systematic surveillance in Egypt, and 53
      viruses that were sequenced previously and available in the public domain.
      Results indicated that H5N1 viruses in Egypt continue to evolve and a new
      distinct cluster has emerged. Mutations affecting viral virulence, pathogenicity,
      transmission, receptor-binding preference and drug resistance were studied. In
      light of our findings that H5N1 in Egypt continues to evolve, surveillance and
      molecular studies need to be sustained. 

PMID- 24722685
TI  - Li-Se battery: absence of lithium polyselenides in carbonate based electrolyte.
AB  - The lithiation mechanism of the Li-Se cell in a carbonate-based electrolyte is
      discussed. It is found that Se is directly reduced to Li2Se in discharge without
      intermediate phases detected by in situ X-ray diffraction or X-ray absorption
      spectroscopy. The reason is that the redox products Se and Li2Se, as well as
      lithium polyselenides are insoluble in the electrolyte. 

PMID- 24722686
TI  - SimpleSTORM: a fast, self-calibrating reconstruction algorithm for localization
      microscopy.
AB  - Although there are many reconstruction algorithms for localization microscopy,
      their use is hampered by the difficulty to adjust a possibly large number of
      parameters correctly. We propose SimpleSTORM, an algorithm that determines
      appropriate parameter settings directly from the data in an initial self
      calibration phase. The algorithm is based on a carefully designed yet simple
      model of the image acquisition process which allows us to standardize each image
      such that the background has zero mean and unit variance. This standardization
      makes it possible to detect spots by a true statistical test (instead of hand
      tuned thresholds) and to de-noise the images with an efficient matched filter. By
      reducing the strength of the matched filter, SimpleSTORM also performs reasonably
      on data with high-spot density, trading off localization accuracy for improved
      detection performance. Extensive validation experiments on the ISBI Localization
      Challenge Dataset, as well as real image reconstructions, demonstrate the good
      performance of our algorithm. 

PMID- 24722687
TI  - An ab initio study of the CrHe diatomic molecule: the effect of van der Waals
      distortion on a highly magnetic multi-electron system.
AB  - The interaction between He and Cr is investigated by means of post-Hartree-Fock
      molecular orbital theory. We analyze the influence of the van der Waals forces on
      the complex electronic structure of the chromium atom, starting with its septet
      manifold and cover the first few electronically excited states up to 30 000 cm(
      1). For the sake of a direct comparison with ongoing experiments on Cr-doped
      helium nanodroplets we extend our analysis to selected states of the quintet
      manifold in order to explain a non-radiating relaxation from y (7)P(o) to z
      (5)P(o).

PMID- 24722688
TI  - Rituximab for refractory digital infarcts and ulcers in systemic sclerosis.
AB  - Systemic sclerosis is an uncommon connective tissue disease characterised by
      excessive deposition of collagen and vasculopathy which affects the skin and
      multiple internal organs. It is associated with autoimmunity, inflammation,
      vasculopathy and fibrosis. Managing Raynaud's phenonemon, digital infarcts and
      ulcers in systemic sclerosis patients is often a challenge particularly among
      rheumatologists. We report a case of systemic sclerosis patient with refractory
      digital infarcts and ulcers responded successfully with rituximab. 

PMID- 24722689
TI  - Impacts of agricultural management and climate change on future soil organic
      carbon dynamics in North China Plain.
AB  - Dynamics of cropland soil organic carbon (SOC) in response to different
      management practices and environmental conditions across North China Plain (NCP)
      were studied using a modeling approach. We identified the key variables driving
      SOC changes at a high spatial resolution (10 km * 10 km) and long time scale (90
      years). The model used future climatic data from the FGOALS model based on four
      future greenhouse gas (GHG) concentration scenarios. Agricultural practices
      included different rates of nitrogen (N) fertilization, manure application, and
      stubble retention. We found that SOC change was significantly influenced by the
      management practices of stubble retention (linearly positive), manure application
      (linearly positive) and nitrogen fertilization (nonlinearly positive) - and the
      edaphic variable of initial SOC content (linearly negative). Temperature had
      weakly positive effects, while precipitation had negligible impacts on SOC
      dynamics under current irrigation management. The effects of increased N
      fertilization on SOC changes were most significant between the rates of 0 and 300
      kg ha-1 yr-1. With a moderate rate of manure application (i.e., 2000 kg ha-1 yr
      1), stubble retention (i.e., 50%), and an optimal rate of nitrogen fertilization
      (i.e., 300 kg ha-1 yr-1), more than 60% of the study area showed an increase in
      SOC, and the average SOC density across NCP was relatively steady during the
      study period. If the rates of manure application and stubble retention doubled
      (i.e., manure application rate of 4000 kg ha-1 yr-1 and stubble retention rate of
      100%), soils across more than 90% of the study area would act as a net C sink,
      and the average SOC density kept increasing from 40 Mg ha-1 during 2010s to the
      current worldwide average of ~ 55 Mg ha-1 during 2060s. The results can help
      target agricultural management practices for effectively mitigating climate
      change through soil C sequestration.

PMID- 24722690
TI  - Transcriptome analysis of the Portunus trituberculatus: de novo assembly, growth
      related gene identification and marker discovery.
AB  - BACKGROUND: The swimming crab, Portunus trituberculatus, is an important farmed
      species in China, has been attracting extensive studies, which require more and
      more genome background knowledge. To date, the sequencing of its whole genome is
      unavailable and transcriptomic information is also scarce for this species. In
      the present study, we performed de novo transcriptome sequencing to produce a
      comprehensive transcript dataset for major tissues of Portunus trituberculatus by
      the Illumina paired-end sequencing technology. RESULTS: Total RNA was isolated
      from eyestalk, gill, heart, hepatopancreas and muscle. Equal quantities of RNA
      from each tissue were pooled to construct a cDNA library. Using the Illumina
      paired-end sequencing technology, we generated a total of 120,137 transcripts
      with an average length of 1037 bp. Further assembly analysis showed that all
      contigs contributed to 87,100 unigenes, of these, 16,029 unigenes (18.40% of the
      total) can be matched in the GenBank non-redundant database. Potential genes and
      their functions were predicted by GO, KEGG pathway mapping and COG analysis.
      Based on our sequence analysis and published literature, many putative genes with
      fundamental roles in growth and muscle development, including actin, myosin,
      tropomyosin, troponin and other potentially important candidate genes were
      identified for the first time in this specie. Furthermore, 22,673 SSRs and 66,191
      high-confidence SNPs were identified in this EST dataset. CONCLUSION: The
      transcriptome provides an invaluable new data for a functional genomics resource
      and future biological research in Portunus trituberculatus. The data will also
      instruct future functional studies to manipulate or select for genes influencing
      growth that should find practical applications in aquaculture breeding programs.
      The molecular markers identified in this study will provide a material basis for
      future genetic linkage and quantitative trait loci analyses, and will be
      essential for accelerating aquaculture breeding programs with this species.

PMID- 24722691
TI  - Predicting kinase activity in angiotensin receptor phosphoproteomes based on
      sequence-motifs and interactions.
AB  - Recent progress in the understanding of seven-transmembrane receptor (7TMR)
      signalling has promoted the development of a new generation of pathway selective
      ligands. The angiotensin II type I receptor (AT1aR) is one of the most studied
      7TMRs with respect to selective activation of the beta-arrestin dependent
      signalling. Two complimentary global phosphoproteomics studies have analyzed the
      complex signalling induced by the AT1aR. Here we integrate the data sets from
      these studies and perform a joint analysis using a novel method for prediction of
      differential kinase activity from phosphoproteomics data. The method builds upon
      NetworKIN, which applies sophisticated linear motif analysis in combination with
      contextual network modelling to predict kinase-substrate associations with high
      accuracy and sensitivity. These predictions form the basis for subsequently
      nonparametric statistical analysis to identify likely activated kinases. This
      suggested that AT1aR-dependent signalling activates 48 of the 285 kinases
      detected in HEK293 cells. Of these, Aurora B, CLK3 and PKG1 have not previously
      been described in the pathway whereas others, such as PKA, PKB and PKC, are well
      known. In summary, we have developed a new method for kinase-centric analysis of
      phosphoproteomes to pinpoint differential kinase activity in large-scale data
      sets.

PMID- 24722692
TI  - The role of endogenous epidermal growth factor receptor ligands in mediating
      corneal epithelial homeostasis.
AB  - PURPOSE: To provide a comprehensive study of the biological role and therapeutic
      potential of six endogenous epidermal growth factor receptor (EGFR) ligands in
      corneal epithelial homeostasis. METHODS: Kinetic analysis and dose response
      curves were performed by using in vitro and in vivo wound-healing assays.
      Biochemical assays were used to determine receptor expression and activity. Human
      tears were collected and quantitatively analyzed by multianalyte profiling for
      endogenous EGFR ligands. RESULTS: Epidermal growth factor receptor ligands
      improved wound closure and activated EGFR, but betacellulin (BTC) was the most
      efficacious promoter of wound healing in vitro. In contrast, only epidermal
      growth factor (EGF) promoted wound healing in vivo. Human tears from 25 healthy
      individuals showed EGFR ligands at these average concentrations: EGF at 2053 +/-
      312.4 pg/mL, BTC at 207 +/- 39.4 pg/mL, heparin-binding EGF at 44 +/- 5.8 pg/mL,
      amphiregulin at 509 +/- 28.8 pg/mL, transforming growth factor-alpha at 84 +/- 19
      pg/mL, and epiregulin at 52 +/- 15 pg/mL. CONCLUSIONS: Under unwounded
      conditions, only EGF was present at concentrations near the ligand's Kd for the
      receptor, indicating it is the primary mediator of corneal epithelial
      homeostasis. Other ligands were present but at concentrations 11- to 7500-fold
      less their Kd, preventing significant ligand binding. Further, the high levels of
      EGF and its predicted binding preclude receptor occupancy by exogenous ligand and
      can explain the discrepancy between the in vitro and in vivo data. Therefore,
      therapeutic use of EGFR ligands may be unpredictable and impractical.

PMID- 24722693
TI  - Effect of reduced retinal VLC-PUFA on rod and cone photoreceptors.
AB  - PURPOSE: Autosomal dominant Stargardt-like macular dystrophy (STGD3) is a
      juvenile-onset disease that is caused by mutations in Elovl4 (elongation of very
      long fatty acids-4). The Elovl4 catalyzes the first step in the conversion of C24
      and longer fatty acids (FAs) to very long-chain FAs (VLC-FAs, >=C26).
      Photoreceptors are particularly rich in VLC polyunsaturated FAs (VLC-PUFA). To
      explore the role of VLC-PUFAs in photoreceptors, we conditionally deleted Elovl4
      in the mouse retina. METHODS: Proteins were analyzed by Western blotting and
      lipids by gas chromatography (GC)-mass spectrometry, GC-flame ionization
      detection, and tandem mass spectrometry. Retina function was assessed by
      electroretinography (ERG), and structure was evaluated by bright field,
      immunofluorescence, and transmission electron microscopy. RESULTS: Conditional
      deletion (KO) of retinal Elovl4 reduced RNA and protein levels by 91% and 96%,
      respectively. Total retina VLC-PUFAs were reduced by 88% compared to the wild
      type (WT) levels. Retinal VLC-PUFAs incorporated in phosphatidylcholine were less
      abundant at 12 months compared to 8-week-old levels. Amplitudes of the ERG a-wave
      were reduced by 22%, consistent with photoreceptor degeneration (11% loss of
      photoreceptors). Analysis of the rod a-wave responses gave no evidence of a role
      for VLC-PUFA in visual transduction. However, there were significant reductions
      in rod b-wave amplitudes (>30%) that could not be explained by loss of rod
      photoreceptors. There was no effect of VLC-PUFA reduction on cone ERG responses,
      and cone density was not different between the WT and KO mice at 12 months of
      age. CONCLUSIONS: The VLC-PUFAs are important for rod, but not cone, function and
      for rod photoreceptor longevity.

PMID- 24722694
TI  - Age distribution of various corneal diseases in China by histopathological
      examination of 3112 surgical specimens.
AB  - PURPOSE: To analyze the age distribution of corneal disease in China by
      histopathological examination. METHODS: A retrospective histopathological
      analysis of the prevalence and age distribution of corneal disease was performed
      on corneal specimens from 3112 patients who underwent corneal surgery between
      2001 and 2012 in the Henan Eye Institute. RESULTS: Infectious keratitis (2212
      specimens, 71.08%) was the most common corneal disease. The distribution of age
      groups was significantly higher after age 30 (16.29%), reaching a peak by age 40
      (22.04%) and remaining high until age 59 (21.05%, P < 0.01). The highest age
      specific percentage of corneal infection was between the ages of 50 and 59
      (83.21%, P < 0.01). Noninfectious corneal diseases occurred mainly in the age
      range of 10 to 19 years (42.47%) and 20 to 29 years (40.78%). Between the ages of
      10 and 19, the leading pathologic diagnosis was keratoconus, accounting for
      21.29% of cases. In patients aged 80 and older, the most common noninfectious
      corneal diseases were Terrien-marginal degeneration (8.33%) and Mooren's ulcer
      (4.17%). The highest incidence of corneal tumor was seen between the ages of 0
      and 9 years (65.83%) and age 80 and older (45.86%; P < 0.01). CONCLUSIONS: The
      age distribution of corneal diseases in the Chinese population is distinct from
      other countries. The corneal diseases tend to increase in prevalence in middle
      age, especially for infectious corneal disease. The prevalence of corneal tumor
      is high in early and late life. Corneal degenerative disease occurs predominately
      in seniors.

PMID- 24722695
TI  - Effects of vitamin D receptor knockout on cornea epithelium gap junctions.
AB  - PURPOSE: Gap junctions are present in all corneal cell types and have been shown
      to have a critical role in cell phenotype determination. Vitamin D has been shown
      to influence cell differentiation, and recent work demonstrates the presence of
      vitamin D in the ocular anterior segment. This study measured and compared gap
      junction diffusion coefficients among different cornea epithelium phenotypes and
      in keratocytes using a noninvasive technique, fluorescence recovery after
      photobleaching (FRAP), and examined the influence of vitamin D receptor (VDR)
      knockout on epithelial gap junction communication in intact corneas. Previous gap
      junction studies in cornea epithelium and keratocytes were performed using
      cultured cells or ex vivo invasive techniques. These invasive techniques were
      unable to measure diffusion coefficients and likely were disruptive to normal
      cell physiology. METHODS: Corneas from VDR knockout and control mice were stained
      with 5(6)-carboxyfluorescein diacetate (CFDA). Gap junction diffusion
      coefficients of the corneal epithelium phenotypes and of keratocytes, residing in
      intact corneas, were detected using FRAP. RESULTS: Diffusion coefficients equaled
      18.7, 9.8, 5.6, and 4.2 MUm(2)/s for superficial squamous cells, middle wing
      cells, basal cells, and keratocytes, respectively. Corneal thickness, superficial
      cell size, and the superficial squamous cell diffusion coefficient of 10-week-old
      VDR knockout mice were significantly lower than those of control mice (P < 0.01).
      The superficial cell diffusion coefficient of heterozygous mice was significantly
      lower than control mice (P < 0.05). CONCLUSIONS: Our results demonstrate
      differences in gap junction dye spread among the epithelial cell phenotypes,
      mirroring the epithelial developmental axis. The VDR knockout influences
      previously unreported cell-to-cell communication in superficial epithelium.

PMID- 24722696
TI  - Therapeutic effects of topical doxycycline in a benzalkonium chloride-induced
      mouse dry eye model.
AB  - PURPOSE: We investigated the therapeutic effects and underlying mechanisms of
      topical doxycycline in a benzalkonium chloride (BAC)-induced mouse dry eye model.
      METHODS: Eye drops containing 0.025%, 0.1% doxycycline or solvent were
      administered to a BAC-induced dry eye model four times daily. The clinical
      evaluations, including tear break-up time (BUT), fluorescein staining,
      inflammatory index, and tear volume, were performed on days 0, 1, 4, 7, and 10.
      Global specimens were collected on day 10 and processed for immunofluorescent
      staining, TUNEL, and periodic acid-Schiff assay. The levels of inflammatory
      mediators in the corneas were determined by real-time PCR. The total and
      phosphorylated nuclear factor-kappaB (NF-kappaB) were detected by Western blot.
      RESULTS: Both 0.025% and 0.1% doxycycline treatments resulted in increased BUT,
      lower fluorescein staining scores, and inflammatory index on days 4, 7, and 10,
      while no significant change in tear volume was observed. The 0.1% doxycycline
      treated group showed more improvements in decreasing fluorescein staining scores,
      increasing Ki-67-positive cells, and decreasing TUNEL- and keratin-10-positive
      cells than other groups. The mucin-filled goblet cells in conjunctivas were
      increased, and the expression of CD11b and levels of matrix metalloproteinase-9,
      IL-1beta, IL-6, TNF-alpha, macrophage inflammatory protein-2, and cytokine
      induced neutrophil chemoattractant in corneas were decreased in both doxycycline
      treated groups. In addition, doxycycline significantly reduced the
      phosphorylation of NF-kappaB activated in the BAC-treated corneas. CONCLUSIONS:
      Topical doxycycline showed clinical improvements and alleviated ocular surface
      inflammation on BAC-induced mouse dry eye, suggesting a potential as an anti
      inflammatory agent in the clinical treatment of dry eye.

PMID- 24722698
TI  - Association of mitochondrial haplogroups H and R with keratoconus in Saudi
      Arabian patients.
AB  - PURPOSE: Keratoconic corneas exhibit more mitochondrial DNA (mtDNA) damage than
      do normal corneas and thus mtDNA may represent a potential candidate for genetic
      susceptibility studies in keratoconus. To test this hypothesis we determined
      mitochondrial haplogroups in Saudi patients with keratoconus and healthy controls
      of same ethnicity. METHODS: Mitochondrial haplogrouping was performed by
      polymerase chain reaction-based automated Sanger sequencing in 114 patients with
      keratoconus and 552 healthy controls. RESULTS: Mitochondrial haplogroups H and R
      were significantly overrepresented in patients with keratoconus (28.9% vs. 8.5%,
      P < 0.0001 and 17.5% vs. 3.1%, P < 0.0001, respectively) as compared to healthy
      controls. CONCLUSIONS: Our data suggest that individuals with mitochondrial
      haplogroups H and R are at increased risk to develop keratoconus. In addition,
      the results provide further evidence for a plausible role of mtDNA in keratoconus
      etiology.

PMID- 24722697
TI  - Pharmacologic alternatives to riboflavin photochemical corneal cross-linking: a
      comparison study of cell toxicity thresholds.
AB  - PURPOSE: The efficacy of therapeutic cross-linking of the cornea using riboflavin
      photochemistry (commonly abbreviated as CXL) has caused its use to become
      widespread. Because there are known chemical agents that cross-link collagenous
      tissues, it may be possible to cross-link tissue pharmacologically. The present
      study was undertaken to compare the cell toxicity of such agents. METHODS: Nine
      topical cross-linking agents (five nitroalcohols, glyceraldehyde [GLYC], genipin
      [GP], paraformaldehyde [FA], and glutaraldehyde [GLUT]) were tested with four
      different cell lines (immortalized human corneal epithelial cells, human skin
      fibroblasts, primary bovine corneal endothelial cells, and immortalized human
      retinal pigment epithelial cells [ARPE-19]). The cells were grown in planar
      culture and exposed to each agent in a range of concentrations (0.001 mM to 10
      mM) for 24 hours followed by a 48-hour recovery phase. Toxicity thresholds were
      determined by using the trypan blue exclusion method. RESULTS: A semiquantitative
      analysis using five categories of toxicity/fixation was carried out, based on
      plate attachment, uptake of trypan blue stain, and cellular fixation. The
      toxicity levels varied by a factor of 10(3) with the least toxic being
      mononitroalcohols and GLYC, intermediate toxicity for a nitrodiol and nitrotriol,
      and the most toxic being GLUT, FA, GP, and bronopol, a brominated nitrodiol. When
      comparing toxicity between different cell lines, the levels were generally in
      agreement. CONCLUSIONS: There are significant differences in cell toxicity among
      potential topical cross-linking compounds. The balance between cross-linking of
      tissue and cell toxicity should be borne in mind as compounds and strategies to
      improve mechanical tissue properties through therapeutic tissue cross-linking
      continue to develop.

PMID- 24722699
TI  - Structure-function correlations in glaucoma using matrix and standard automated
      perimetry versus time-domain and spectral-domain OCT devices.
AB  - PURPOSE: We examined the structure-function relationship between two perimetric
      tests, the frequency doubling technology (FDT) matrix and standard automated
      perimetry (SAP), and two optical coherence tomography (OCT) devices (time-domain
      and spectral-domain). METHODS: This cross-sectional study included 97 eyes from
      29 healthy individuals, and 68 individuals with early, moderate, or advanced
      primary open-angle glaucoma. The correlations between overall and sectorial
      parameters of retinal nerve fiber layer thickness (RNFL) measured with Stratus
      and Spectralis OCT, and the visual field sensitivity obtained with FDT matrix and
      SAP were assessed. The relationship also was evaluated using a previously
      described linear model. RESULTS: The correlation coefficients for the threshold
      sensitivity measured with SAP and Stratus OCT ranged from 0.44 to 0.79, and those
      for Spectralis OCT ranged from 0.30 to 0.75. Regarding FDT matrix, the
      correlation ranged from 0.40 to 0.79 with Stratus OCT and from 0.39 to 0.79 with
      Spectralis OCT. Stronger correlations were found in the overall measurements and
      the arcuate sectors for both visual fields and OCT devices. A linear relationship
      was observed between FDT matrix sensitivity and the OCT devices. The previously
      described linear model fit the data from SAP and the OCT devices well,
      particularly in the inferotemporal sector. CONCLUSIONS: The FDT matrix and SAP
      visual sensitivities were related strongly to the RNFL thickness measured with
      the Stratus and Spectralis OCT devices, particularly in the overall and arcuate
      sectors.

PMID- 24722700
TI  - An investigation of lateral geniculate nucleus volume in patients with primary
      open-angle glaucoma using 7 tesla magnetic resonance imaging.
AB  - PURPOSE: To investigate lateral geniculate nucleus (LGN) volume of primary open
      angle glaucoma (POAG) patients compared with age- and sex-matched controls using
      ultra-high field 7.0-T magnetic resonance imaging (MRI). METHODS: The study
      included 18 patients with POAG and 18 age- and sex-matched healthy volunteers.
      All subjects underwent imaging on a high-resolution 7.0-T MRI system. Bilateral
      LGNs were identified and manually delineated, and LGN volumes were compared.
      Peripapillary retinal nerve fiber layer (pRNFL) thickness, optic nerve head
      parameters (including optic disc size, rim area, and cup-to-disc ratio), and
      combined thickness of the ganglion cell layer and inner plexus layer (GC-IPL)
      were measured by Cirrus high-definition optical coherence tomography (OCT).
      Correlations between OCT parameters and LGN volume were investigated. RESULTS:
      Mean LGN volumes were significantly smaller in the POAG group than in the control
      group (right, glaucoma 83.97 mm(3) [SD +/- 26.65] versus control 106.12 mm(3) [SD
      +/- 24.32]; left, glaucoma 65.12 mm(3) [SD +/- 29.41] versus control 92.70 mm(3)
      [SD +/- 24.42], both P < 0.05). In the POAG group, average GC-IPL thickness was
      correlated with contralateral LGN volume (right LGN: r = 0.605, P = 0.008; left
      LGN: r = 0.471, P = 0.049). The correlation for right LGN volume remained
      significant after correction for multiple comparisons. However, there was no
      correlation between LGN volume and average pRNFL thickness or optic disc
      parameters in the POAG group. CONCLUSIONS: On high-resolution 7.0-T MRI, LGN
      volumes in POAG patients are significantly smaller than those of healthy
      subjects. Furthermore, in patients, LGN volume was found to be significantly
      correlated with GC-IPL thickness of the contralateral eye.

PMID- 24722702
TI  - Update in hospital medicine: evidence published in 2013.

PMID- 24722701
TI  - Complement-related proteins control the flavivirus infection of Aedes aegypti by
      inducing antimicrobial peptides.
AB  - The complement system functions during the early phase of infection and directly
      mediates pathogen elimination. The recent identification of complement-like
      factors in arthropods indicates that this system shares common ancestry in
      vertebrates and invertebrates as an immune defense mechanism. Thioester (TE)
      containing proteins (TEPs), which show high similarity to mammalian complement
      C3, are thought to play a key role in innate immunity in arthropods. Herein, we
      report that a viral recognition cascade composed of two complement-related
      proteins limits the flaviviral infection of Aedes aegypti. An A. aegypti
      macroglobulin complement-related factor (AaMCR), belonging to the insect TEP
      family, is a crucial effector in opposing the flaviviral infection of A. aegypti.
      However, AaMCR does not directly interact with DENV, and its antiviral effect
      requires an A. aegypti homologue of scavenger receptor-C (AaSR-C), which
      interacts with DENV and AaMCR simultaneously in vitro and in vivo. Furthermore,
      recognition of DENV by the AaSR-C/AaMCR axis regulates the expression of
      antimicrobial peptides (AMPs), which exerts potent anti-DENV activity. Our
      results both demonstrate the existence of a viral recognition pathway that
      controls the flaviviral infection by inducing AMPs and offer insights into a
      previously unappreciated antiviral function of the complement-like system in
      arthropods. 

PMID- 24722703
TI  - Radioimmunotherapy for first-line and relapse treatment of aggressive B-cell non
      Hodgkin lymphoma: an analysis of 215 patients registered in the international RIT
      Network.
AB  - PURPOSE: Very few reliable clinical data about the use of radioimmunotherapy in
      aggressive B-cell lymphoma exist. METHODS: Patients with aggressive B-cell
      lymphoma registered in the international RIT-Network were analysed with regard to
      prior treatment, response and side effects. The RIT-Network is a web-based
      registry that collects observational data from radioimmunotherapy-treated
      patients with malignant lymphoma across 13 countries. RESULTS: This analysis
      included 215 with aggressive B-cell lymphoma out of 232 patients registered in
      the RIT-Network. Histological subtypes were as follows: 190 diffuse large B-cell,
      15 primary mediastinal, 9 anaplastic large cell, and 1 intravascular lymphoma.
      The median age of the patients was 62 years (range 17 - 88), with 27% above the
      age of 70 years. Radioimmunotherapy was mainly used as consolidation after first
      line or second-line chemotherapy (56.1%), as part of third-line to eighth-line
      therapy for relapse (16.4%), and in refractory disease (12.2%). Grade IV
      neutropenia and thrombopenia and grade III anaemia were observed. The median time
      to recovery of blood count was 81 days (range 0 - 600 days). The overall response
      rate was 63.3%. The complete response rate was 76.4 % in patients treated as part
      of first-line therapy, and 44.3% in patients with relapse. Mean overall survival
      in first-line therapy patients was 32.7 months and 14.0 months in patients with
      relapse or refractory disease, respectively. CONCLUSION: Most patients with
      aggressive B-cell lymphoma in the RIT-Network received radioimmunotherapy as
      consolidation after first-line therapy with excellent complete remission and
      overall survival rates compared to published data. In relapsed aggressive B-cell
      lymphoma, radioimmunotherapy is a safe and feasible treatment leading to
      satisfactory response rates with acceptable toxicity.

PMID- 24722706
TI  - De Garengeot hernia: a forgotten rare entity?
AB  - We report the case of a 79-year-old woman who presented with an increasingly
      painful lump in her right groin for 24 h. An incidental femoral hernia was
      detected on her CT scan nearly 8 months ago while investigating her medical
      conditions. However, its management was deferred on account of ongoing medical
      illness. Exploration of the lump revealed a gangrenous appendix strangulated
      within the femoral canal (de Garengeot hernia). The hernia was repaired primarily
      after appendicectomy. The patient was discharged after making an uneventful
      recovery. 

PMID- 24722707
TI  - Postangioedema attack skin blisters: an unusual presentation of hereditary
      angioedema.
AB  - Hereditary angioedema (HAE) is an autosomal dominant disorder characterised by
      attacks of self-limited swelling affecting extremities, face and intra-abdominal
      organs, most often caused by mutations in the C1-inhibitor gene with secondary
      Bradykinin-mediated increased vascular permeability. We describe a 36-year-old
      man with a history of HAE who presented with painful interdigital bullae
      secondary to an acute oedema exacerbation. Biopsy and cultures of the lesions
      were negative and they resolved spontaneously. It is important to highlight and
      recognise the development of oedema blisters after resolution of a flare of HAE
      (only 1 previous case report), and hence avoid unnecessary dermatological
      diagnostic workup and treatment. 

PMID- 24722708
TI  - Single stage substernal thyroidectomy and off-pump coronary artery bypass
      grafting: is it worth using cardiopulmonary bypass unless absolutely necessary?
AB  - It is a rare entity to observe the coexistence of thyroid gland pathologies and
      coronary artery disease, whose surgical treatment may be performed
      simultaneously. In this case, we present a case of a patient with substernal
      thyroidectomy concurrent with off-pump coronary artery bypass grafting. A 57-year
      old female patient was admitted to the hospital with exertional dyspnoea,
      intermittent coughing and stable angina pectoris. The substernal goitre measuring
      5*5*4 cm was accompanied by a 95% in-stent restenosis at the left anterior
      descending artery. Thyroidectomy and off-pump coronary artery bypass grafting
      procedures were performed simultaneously. The postoperative period was uneventful
      and the patient was discharged 5 days after the operation. This case indicates
      that off-pump revascularisation seems to be a better option in cases where
      surgical interventions for thyroid and coronary artery diseases are necessary
      instead of on-pump revascularisation where the adverse effects of the
      cardiopulmonary bypass are considered. 

PMID- 24722709
TI  - Adenomyosis in pregnancy mimicking morbidly adherent placenta.
AB  - The objective of this study was to illustrate a false-positive diagnosis of
      adherent placenta due to underlying adenomyosis. A 34-year-old woman was
      diagnosed for placenta previa totalis with adherent placenta at 33 weeks, based
      on the findings of loss of clear space or distinguishing outline separating the
      placenta and uterine wall, presence of intraplacental lacunae and densely
      atypical vessels in the lesion. Caesarean hysterectomy was performed at 35 weeks.
      Pathological findings revealed placenta previa totalis with adenomyosis beneath
      the placenta at the lower segment, with no adherent placenta. In conclusion, this
      report underlines the importance of possible false-positive test of prenatal
      ultrasound and MRI findings of adherent placenta caused by underlying adenomyosis
      which could obliterate the outline distinguishing the placenta and myometrium and
      atypical vessels secondary to decidualisation and hypervascularity from
      pregnancy. This case may probably encourage physician to beware of false-positive
      test of adherent placenta due to adenomyosis. 

PMID- 24722711
TI  - Non-surgical treatment of skeletal class III malocclusion.
AB  - The incidence of skeletal class III malocclusion has a mean of 3% in the
      Caucasian population, 5% in African-American adolescents and about 14% in the
      Asian population. In India, the incidence of class III malocclusion is reported
      to be 3.4%. A patient having class III malocclusion shows findings ranging from
      edge-to-edge bite to large reverse overjet, with extreme variations of underlying
      skeletal jaw bases and craniofacial form. This is a case report of a 20-year-old
      man having skeletal class III malocclusion with concave profile, anterior
      crossbite and a negative overjet of 3 mm treated non-surgically with extraction
      of only one lower left first premolar. 

PMID- 24722712
TI  - CANOMAD responding to weekly treatment with intravenous immunoglobulin (IVIg).
AB  - A 48-year-old man presented with numbness in fingers and diplopia 1 week after a
      flu-like illness. He made a full recovery but 8 years later developed progressive
      and disabling sensory ataxia. He had superimposed acute flare-ups with numbness,
      double vision and ptosis, all following infections. A blood test showed
      antidisialosyl antibodies including GD1b, GD3, GT1b and GQ1b in keeping with the
      diagnosis of chronic ataxic neuropathy, ophthalmoplegia, IgM paraprotein, cold
      agglutinins and antidisialosyl antibodies (CANOMAD). Initial treatment with
      monthly courses of intravenous immunoglobulin (IVIg) 0.4 g/kg/day for 5 days
      every 4 weeks helped temporarily but there were marked disabling fluctuations of
      symptoms. With IVIg 0.6 g/kg/day weekly his symptoms are stable. He remains
      mobile and has no eye symptoms without need for any other medication. This case
      demonstrates that weekly IVIg infusions instead of one 5-day course monthly may
      be able to avoid fluctuations of symptoms in CANOMAD. 

PMID- 24722713
TI  - Where is the right ventricle?

PMID- 24722714
TI  - An 'appendiceal colic' caused by the Enterobius vermicularis.

PMID- 24722715
TI  - Alveolar soft part sarcoma.
AB  - Alveolar soft part sarcoma (ASPS) is a rare form of soft tissue sarcoma and is
      most often seen in adolescents and young adults. Despite its unique histology and
      well-characterised genetic translocation, many questions remain regarding the
      pathogenesis and treatment of this tumour type. Surgical excision of the primary
      tumour and pulmonary metastases has resulted in prolonged survival of some
      patients while the benefit of adjuvant chemotherapy and/or radiotherapy has been
      disputed. A 35-year-old woman presented with a tumour in the right leg and right
      side of the mandible along with active metastasis to lungs and multiple skeletal
      sites. 

PMID- 24722717
TI  - CNS intravascular lymphoma: an underappreciated cause of rapidly progressive
      dementia.
AB  - Intravascular lymphoma is a rare subtype of extranodal large cell non-Hodgkin's
      lymphoma that is usually seen in the elderly. It can occasionally present with
      neurological symptoms in the form of dementia, focal neurological deficit and
      seizure. Diagnosis is difficult because of non-specific clinical manifestation.
      We report a case of a 38-year-old woman presenting with rapidly progressive
      dementia and seizure. MRI of the brain showed bilateral diffuse involvement of
      cortex and subcortical white matter. Brain biopsy disclosed the aetiological
      confirmation of intravascular B-cell lymphoma. The patient was treated with
      monthly cyclophosphamide, doxorubicin, vincristine and prednisolone regimen, but
      unfortunately, she died after two chemotherapy cycles. So, high index of
      suspicion is warranted to diagnose and treat the condition early to have a better
      outcome. 

PMID- 24722718
TI  - Holt-Oram: when the key to a broken heart is in the hand.

PMID- 24722719
TI  - Sodium valproate-related hyperammonaemic encephalopathy.
AB  - A 59-year-old man with a background of poststroke epilepsy, lung cancer, chronic
      obstructive pulmonary disease and hypertension, presented to the medical
      assessment unit with acute confusion and altered consciousness. Medications
      included sodium valproate, aspirin and antihypertensives. On examination he was
      confused, with his Glasgow Coma Scale fluctuating between 10 and 14. Routine
      blood tests, thyroid function tests, serum sodium valproate level, urine dip, CT
      of the brain and cerebrospinal fluid analysis were all normal. EEG revealed
      changes consistent with an encephalopathic process. Serum ammonia was elevated
      (75 ug/dL), consistent with a diagnosis of valproate-related hyperammonaemic
      encephalopathy. Sodium valproate was changed to a different antiepileptic drug
      and his confusion gradually resolved. Valproate-related hyperammonaemic
      encephalopathy is a treatable condition which should be considered as a diagnosis
      in anyone taking sodium valproate with new onset confusion, even in the presence
      of therapeutic sodium valproate levels and normal liver function tests. 

PMID- 24722720
TI  - Lipoid proteinosis: pathognomonic clinical and radiological features.
AB  - A 22-year-old woman presented with a facial rash and hoarseness of voice. On
      examination, coarse waxy thickening and scarring was noted on the forehead and
      both the cheeks. The eyelid margins revealed a row of beaded papules termed
      'moniliform blepharosis'. CT scan of the brain revealed bilateral, symmetric
      calcification of the amygdala of the hippocampal nuclei. This led to the
      diagnosis of lipoid proteinosis which is a rare genetic disorder. 

PMID- 24722721
TI  - Concurrent flexor carpi radialis tendon rupture and closed distal radius
      fracture.
AB  - Tendon rupture as a complication of distal radius fractures has been documented;
      however, flexor tendon rupture associated with closed distal radius fractures is
      rare. We report a case of a 43-year-old man who suffered a closed distal radius
      fracture. Intraoperatively, it was discovered that the flexor carpi radialis
      tendon had ruptured. From the frayed ends of the tendon and review of the
      radiographs, it was determined that the sharp ends of the fractured radius had
      lacerated the tendon at the time of injury. After fixation of the fracture with
      locking plate, the severed tendon was repaired and the wrist immobilised with a
      splint. The patient has been pain free after 5 months of follow-up, with full
      range of motion. This outcome demonstrates that timely detection and treatment of
      concurrent flexor carpi radialis tendon rupture and a closed distal radius
      fracture can achieve good functional results and outcome. 

PMID- 24722722
TI  - Acetabular fracture following penetration of buttock by railing spike: an unusual
      mechanism of injury needing careful immediate care.

PMID- 24722723
TI  - An endless line on the chest radiograph.
AB  - A 40-year-old male patient had his right femoral vein catheterised following
      admission with altered conscious state from polypharmacy overdose. The procedure
      was documented as successful and uncomplicated. A postprocedural chest radiograph
      demonstrated a linear metallic opacity projecting over the superior vena cava and
      inferior vena cava (SVC and IVC, respectively), with superior and inferior ends
      not visualised. This did not alert the attending radiologist and intensivist who
      might have assumed such a metallic object to be external to the patient. Only the
      central line was removed prior to patient discharge 2 days later. The patient
      died 2 years later from unrelated streptococcal pneumonia complicated by
      septicaemia and multiorgan failure. The postmortem discovered a central venous
      guidewire in the IVC across the right atrium into SVC. 

PMID- 24722724
TI  - Laparoscopic liver resection: lessons learnt after 100 cases.
AB  - OBJECTIVE: To share our institutional experience in laparoscopic liver resection
      and our learning curve after the first 100 cases of laparoscopic liver resection.
      DESIGN: Case series with internal comparison. SETTING: A regional hospital in
      Hong Kong. PATIENTS: Our institution started performing laparoscopic liver
      resection since 2006. All patients who underwent laparoscopic liver resections
      from March 2006 to October 2012 were identified in a prospectively collected
      database. The demographic data and operative outcomes of these patients were
      extracted, and results of the early (from March 2006 to May 2010) and late (from
      June 2010 to October 2012) study periods were compared. RESULTS: Between March
      2006 and October 2012, 100 laparoscopic liver resections were performed for 98
      patients in the Department of Surgery, Kwong Wah Hospital, Hong Kong. They were
      69 (70%) males and 29 (30%) females, and the median age was 65 years. The final
      histological diagnoses were as follows: hepatocellular carcinoma (n=72),
      colorectal liver metastases (n=14), intrahepatic cholangiocarcinoma (n=4), and
      benign disease (n=10). There were more anatomical resections, major hepatectomies
      as well as resections of more anatomically challenging right-sided and
      posterosuperior lesions in the late versus the early period; however, operative
      outcomes remained comparable in both periods. CONCLUSION: Laparoscopic
      hepatectomies are feasible with growing experience. Bearing in mind the diversity
      in the level of operative techniques with various types of laparoscopic liver
      resections, more experience is needed to overcome the learning curve.

PMID- 24722725
TI  - Palladium-catalyzed synthesis of polysubstituted quinolines from 2-amino aromatic
      ketones and alkynes.
AB  - A palladium-catalyzed one-pot method for the synthesis of quinolines from
      commercial or readily available 2-amino aromatic ketones and alkynes is reported
      for the first time. This transformation offers an alternative method for the
      synthesis of polysubstituted quinoline. 

PMID- 24722727
TI  - Evaluating steady-state and time-resolved fluorescence as a tool to study the
      behavior of asphaltene in toluene.
AB  - A combination of steady-state fluorescence, fluorescence lifetime measurements
      and the determination of time-resolved emission spectra were employed to
      characterize asphaltene toluene solutions. Lifetime measurements were shown to be
      insensitive to the source of asphaltene or the alkane solvent from which
      asphaltene was precipitated. This insensitivity suggests that either the
      composition of Athabasca and Cold Lake asphaltene is very similar or that the
      fluorescence behavior is dominated by the same sub-set of fluorophores for the
      different samples. These results highlight the limitations in using fluorescence
      to characterize asphaltene solutions. Different dependencies were observed for
      the average lifetimes with the asphaltene concentration when measured at two
      different emission wavelengths (420 nm and 520 nm). This result suggests that
      different fluorophores underwent diverse interactions with other asphaltene
      molecules as the asphaltene concentration was raised, suggesting that models for
      asphaltene aggregation need to include molecular diversity. 

PMID- 24722726
TI  - Recombination in the evolution of enterovirus C species sub-group that contains
      types CVA-21, CVA-24, EV-C95, EV-C96 and EV-C99.
AB  - Genetic recombination is considered to be a very frequent phenomenon among
      enteroviruses (Family Picornaviridae, Genus Enterovirus). However, the
      recombination patterns may differ between enterovirus species and between types
      within species. Enterovirus C (EV-C) species contains 21 types. In the capsid
      coding P1 region, the types of EV-C species cluster further into three sub-groups
      (designated here as A-C). In this study, the recombination pattern of EV-C
      species sub-group B that contains types CVA-21, CVA-24, EV-C95, EV-C96 and EV-C99
      was determined using partial 5'UTR and VP1 sequences of enterovirus strains
      isolated during poliovirus surveillance and previously published complete genome
      sequences. Several inter-typic recombination events were detected. Furthermore,
      the analyses suggested that inter-typic recombination events have occurred mainly
      within the distinct sub-groups of EV-C species. Only sporadic recombination
      events between EV-C species sub-group B and other EV-C sub-groups were detected.
      In addition, strict recombination barriers were inferred for CVA-21 genotype C
      and CVA-24 variant strains. These results suggest that the frequency of inter
      typic recombinations, even within species, may depend on the phylogenetic
      position of the given viruses. 

PMID- 24722728
TI  - Charting the mechanism and reactivity of zirconium oxalate with hydroxamate
      ligands using density functional theory: implications in new chelate design.
AB  - The reaction of [(89)Zr(C2O4)4](4-) with the tris-hydroxamate ligand
      desferrioxamine B (DFO) provides the basis of radiolabelling biological vectors
      such as antibodies and proteins with the radionuclide (89)Zr for positron
      emission tomography imaging. In this work, density functional theory methods were
      used to investigate the mechanism of reaction from [Zr(C2O4)4](4-) to Zr(MeAHA)4
      by ligand substitution with N-methyl acetohydroxamate (MeAHA). Calculations were
      performed under simulated basic and acidic conditions. Ligand substitution under
      basic conditions was found to be thermodynamically feasible with an overall
      calculated change in solvation free energy, DeltaGsol = -97 kJ mol(-1) using the
      B3LYP/DGDZVP methodology and a water continuum solvation model. In contrast, an
      acid-mediated mechanism of ligand substitution was found to be thermodynamically
      non-feasible. Molecular orbital analysis provides a rationale for the difference
      in thermodynamic stability between [Zr(C2O4)4](4-) and Zr(MeAHA)4. Overall, the
      DFT calculations are consistent with observed experimental (89)Zr-radiolabelling
      reactions and suggest that computational methods may prove useful in designing
      novel chelates for increasing the thermodynamic and kinetic stability of (89)Zr
      complexes in vivo. 

PMID- 24722729
TI  - Designing and understanding permanent microporosity in liquids.
AB  - Standard microporous materials are typically crystalline solids that exhibit a
      regular array of cavities of uniform size and shape. Packing and directional
      bonding between molecular building blocks give rise to interstitial pores that
      confer size and shape-specific sorption properties to the material. In the liquid
      state interstitial cavities are transient. However, permanent and intrinsic
      "pores" can potentially be built into the structure of the molecules that
      constitute the liquid. With the aid of computer simulations we have designed,
      synthesised and characterised a series of liquids composed of hollow cage-like
      molecules, which are functionalised with hydrocarbon chains to make them liquid
      at accessible temperatures. Experiments and simulations demonstrate that chain
      length and size of terminal chain substituents can be used to tune, within
      certain margins, the permanence of intramolecular cavities in such neat liquids.
      Simulations identify a candidate "porous liquid" in which 30% of the cages remain
      empty in the liquid state. Absorbed methane molecules selectively occupy these
      empty cavities. 

PMID- 24722730
TI  - Update in pulmonary, sleep, and critical care medicine: evidence published in
      2013.

PMID- 24722731
TI  - Immunoproteomics using polyclonal antibodies and stable isotope-labeled affinity
      purified recombinant proteins.
AB  - The combination of immuno-based methods and mass spectrometry detection has great
      potential in the field of quantitative proteomics. Here, we describe a new method
      (immuno-SILAC) for the absolute quantification of proteins in complex samples
      based on polyclonal antibodies and stable isotope-labeled recombinant protein
      fragments to allow affinity enrichment prior to mass spectrometry analysis and
      accurate quantification. We took advantage of the antibody resources publicly
      available from the Human Protein Atlas project covering more than 80% of all
      human protein-coding genes. Epitope mapping revealed that a majority of the
      polyclonal antibodies recognized multiple linear epitopes, and based on these
      results, a semi-automated method was developed for peptide enrichment using
      polyclonal antibodies immobilized on protein A-coated magnetic beads. A protocol
      based on the simultaneous multiplex capture of more than 40 protein targets
      showed that approximately half of the antibodies enriched at least one functional
      peptide detected in the subsequent mass spectrometry analysis. The approach was
      further developed to also generate quantitative data via the addition of heavy
      isotope-labeled recombinant protein fragment standards prior to trypsin
      digestion. Here, we show that we were able to use small amounts of antibodies (50
      ng per target) in this manner for efficient multiplex analysis of quantitative
      levels of proteins in a human HeLa cell lysate. The results suggest that
      polyclonal antibodies generated via immunization of recombinant protein fragments
      could be used for the enrichment of target peptides to allow for rapid mass
      spectrometry analysis taking advantage of a substantial reduction in sample
      complexity. The possibility of building up a proteome-wide resource for immuno
      SILAC assays based on publicly available antibody resources is discussed. 

PMID- 24722732
TI  - Controlling for gene expression changes in transcription factor protein networks.
AB  - The development of affinity purification technologies combined with mass
      spectrometric analysis of purified protein mixtures has been used both to
      identify new protein-protein interactions and to define the subunit composition
      of protein complexes. Transcription factor protein interactions, however, have
      not been systematically analyzed using these approaches. Here, we investigated
      whether ectopic expression of an affinity tagged transcription factor as bait in
      affinity purification mass spectrometry experiments perturbs gene expression in
      cells, resulting in the false positive identification of bait-associated proteins
      when typical experimental controls are used. Using quantitative proteomics and
      RNA sequencing, we determined that the increase in the abundance of a set of
      proteins caused by overexpression of the transcription factor RelA is not
      sufficient for these proteins to then co-purify non-specifically and be
      misidentified as bait-associated proteins. Therefore, typical controls should be
      sufficient, and a number of different baits can be compared with a common set of
      controls. This is of practical interest when identifying bait interactors from a
      large number of different baits. As expected, we found several known RelA
      interactors enriched in our RelA purifications (NFkappaB1, NFkappaB2, Rel, RelB,
      IkappaBalpha, IkappaBbeta, and IkappaBepsilon). We also found several proteins
      not previously described in association with RelA, including the small
      mitochondrial chaperone Tim13. Using a variety of biochemical approaches, we
      further investigated the nature of the association between Tim13 and NFkappaB
      family transcription factors. This work therefore provides a conceptual and
      experimental framework for analyzing transcription factor protein interactions. 

PMID- 24722733
TI  - Viscoelastic parameters for quantifying liver fibrosis: three-dimensional
      multifrequency MR elastography study on thin liver rat slices.
AB  - OBJECTIVE: To assess in a high-resolution model of thin liver rat slices which
      viscoelastic parameter at three-dimensional multifrequency MR elastography has
      the best diagnostic performance for quantifying liver fibrosis. MATERIALS AND
      METHODS: The study was approved by the ethics committee for animal care of our
      institution. Eight normal rats and 42 rats with carbon tetrachloride induced
      liver fibrosis were used in the study. The rats were sacrificed, their livers
      were resected and three-dimensional MR elastography of 5 +/- 2 mm liver slices
      was performed at 7T with mechanical frequencies of 500, 600 and 700 Hz. The
      complex shear, storage and loss moduli, and the coefficient of the frequency
      power law were calculated. At histopathology, fibrosis and inflammation were
      assessed with METAVIR score, fibrosis was further quantified with morphometry.
      The diagnostic value of the viscoelastic parameters for assessing fibrosis
      severity was evaluated with simple and multiple linear regressions, receiver
      operating characteristic analysis and Obuchowski measures. RESULTS: At simple
      regression, the shear, storage and loss moduli were associated with the severity
      of fibrosis. At multiple regression, the storage modulus at 600 Hz was the only
      parameter associated with fibrosis severity (r = 0.86, p<0.0001). This parameter
      had an Obuchowski measure of 0.89+/-0.03. This measure was significantly larger
      than that of the loss modulus (0.78+/-0.04, p = 0.028), but not than that of the
      complex shear modulus (0.88+/-0.03, p = 0.84). CONCLUSION: Our high resolution,
      three-dimensional multifrequency MR elastography study of thin liver slices shows
      that the storage modulus is the viscoelastic parameter that has the best
      association with the severity of liver fibrosis. However, its diagnostic
      performance does not differ significantly from that of the complex shear modulus.

PMID- 24722734
TI  - Differential expression of superoxide dismutase genes in aphid-stressed maize
      (Zea mays L.) seedlings.
AB  - The aim of this study was to compare the expression patterns of superoxide
      dismutase genes (sod2, sod3.4, sod9 and sodB) in seedling leaves of the Zea mays
      L. Tasty Sweet (susceptible) and Ambrozja (relatively resistant) cultivars
      infested with one of two hemipteran species, namely monophagous Sitobion avenae
      F. (grain aphid) or oligophagous Rhopalosiphum padi L. (bird cherry-oat aphid).
      Secondarily, aphid-elicited alternations in the antioxidative capacity towards
      DPPH (1,1-diphenyl-2-picrylhydrazyl) radical in insect-stressed plants were
      evaluated. Comprehensive comparison of expression profiles of the four sod genes
      showed that both insect species evoked significant upregulation of three genes
      sod2, sod3.4 and sod9). However, aphid infestation affected non-significant
      fluctuations in expression of sodB gene in seedlings of both maize genotypes. The
      highest levels of transcript accumulation occurred at 8 h (sod2 and sod3.4) or 24
      h (sod9) post-infestation, and aphid-induced changes in the expression of sod
      genes were more dramatic in the Ambrozja cultivar than in the Tasty Sweet
      variety. Furthermore, bird cherry-oat aphid colonization had a more substantial
      impact on levels of DPPH radical scavenging activity in infested host seedlings
      than grain aphid colonization. Additionally, Ambrozja plants infested by either
      hemipteran species showed markedly lower antioxidative capacity compared with
      attacked Tasty Sweet plants.

PMID- 24722735
TI  - Replication study of ESCC susceptibility genetic polymorphisms locating in the
      ADH1B-ADH1C-ADH7 cluster identified by GWAS.
AB  - China was one of the countries with highest esophageal squamous cell carcinoma
      (ESCC) incidence and mortality worldwide. Alcohol drinking has been identified as
      a major environmental risk-factor related to ESCC. The alcohol dehydrogenase
      (ADH) family are major enzymes involved in the alcohol-metabolizing pathways,
      including alcohol dehydrogenase 1B (ADH1B) and ADH1C. Interestingly, ADH1B and
      ADH1C genes locate tandemly with ADH7 in a genomic segment as a gene cluster, and
      are all polymorphic. Several ESCC susceptibility single nucleotide polymorphisms
      (SNPs) of the ADH1B-ADH1C-ADH7 cluster have been identified previously through a
      genome-wide association study (GWAS). In the study, we examined the association
      between five ADH1B-ADH1C-ADH7 cluster SNPs (rs1042026, rs17033, rs1614972,
      rs1789903 and rs17028973) and risk of developing ESCC. Genotypes were determined
      in two independent case-control sets from two regions of China. Odds ratios (ORs)
      and 95% confidence intervals (CIs) were estimated by logistic regression. Our
      data demonstrated that these ADH1B-ADH1C-ADH7 cluster SNPs confer susceptibility
      to ESCC in these two case-control sets, which were consistent to results of the
      previous GWAS. 

PMID- 24722737
TI  - Simulation comes of age.

PMID- 24722738
TI  - The new world of global health.

PMID- 24722736
TI  - pelo is required for high efficiency viral replication.
AB  - Viruses hijack host factors for their high speed protein synthesis, but
      information about these factors is largely unknown. In searching for genes that
      are involved in viral replication, we carried out a forward genetic screen for
      Drosophila mutants that are more resistant or sensitive to Drosophila C virus
      (DCV) infection-caused death, and found a virus-resistant line in which the
      expression of pelo gene was deficient. Our mechanistic studies excluded the viral
      resistance of pelo deficient flies resulting from the known Drosophila anti-viral
      pathways, and revealed that pelo deficiency limits the high level synthesis of
      the DCV capsid proteins but has no or very little effect on the expression of
      some other viral proteins, bulk cellular proteins, and transfected exogenous
      genes. The restriction of replication of other types of viruses in pelo deficient
      flies was also observed, suggesting pelo is required for high level production of
      capsids of all kinds of viruses. We show that both pelo deficiency and high level
      DCV protein synthesis increase aberrant 80S ribosomes, and propose that the
      preferential requirement of pelo for high level synthesis of viral capsids is at
      least partly due to the role of pelo in dissociation of stalled 80S ribosomes and
      clearance of aberrant viral RNA and proteins. Our data demonstrated that pelo is
      a host factor that is required for high efficiency translation of viral capsids
      and targeting pelo could be a strategy for general inhibition of viral infection.

PMID- 24722739
TI  - Towards a global framework for capacity building for non-communicable disease
      advocacy in low- and middle-income countries.
AB  - Non-communicable diseases (NCDs) represent an increasing proportion of morbidity
      and mortality throughout the world. Sustained advocacy, carried out by a skilled
      workforce, is an important strategy to realize the political will and implement
      the policy changes necessary to reduce the global burden of NCDs. Competencies
      for effective advocacy include a combination of scientific and technical as well
      as communication-based skills. Recognizing the need to build local capacity for
      NCD advocacy in low- and middle-income countries (LMIC), the International Union
      for Health Promotion and Education (IUHPE), the US Centers for Disease Control
      and Prevention (CDC), the National Heart Foundation of Australia and the
      InterAmerican Heart Foundation joined efforts to conduct two pilot advocacy
      courses, one in Thailand and one in Colombia. A Global Advisory Group engaged a
      Local Organizing Committee in each country to ensure the courses would meet the
      needs of the local stakeholders. While both courses contained a set of key
      competencies and helped participants develop joint strategies for moving forward
      with consensus advocacy targets, the courses differed in content and participant
      background depending on the local context. A key goal of the courses was to
      determine and describe the lessons learned and make recommendations for a
      framework to be used for future advocacy capacity-building activities in LMIC.
      The planning and execution of each course generated lessons in the following five
      areas that informed the development of a global framework for capacity building
      for NCD advocacy: 1) using a comprehensive theoretical framework to teach
      advocacy competencies, 2) engaging key stakeholders, 3) meeting local needs and
      priorities, 4) planning local logistics, and 5) ensuring the skills obtained
      through training are applied to sustained advocacy for NCDs. 

PMID- 24722740
TI  - Case study: the Argentina Road Safety Project: lessons learned for the decade of
      action for road safety, 2011-2020.
AB  - This case study of the Argentina Road Safety Project demonstrates how the
      application of World Bank road safety project guidelines focused on institution
      building can accelerate knowledge transfer, scale up investment and improve the
      focus on results. The case study highlights road safety as a development priority
      and outlines World Bank initiatives addressing the implementation of the World
      Report on Road Traffic Injury's recommendations and the subsequent launch of the
      Decade of Action for Road Safety, from 2011-2020. The case study emphasizes the
      vital role played by the lead agency in ensuring sustainable road safety
      improvements and promoting the shift to a 'Safe System' approach, which
      necessitated the strengthening of all elements of the road safety management
      system. It summarizes road safety performance and institutional initiatives in
      Argentina leading up to the preparation and implementation of the project. We
      describe the project's development objectives, financing arrangements, specific
      components and investment staging. Finally, we discuss its innovative features
      and lessons learned, and present a set of supplementary guidelines, both to
      assist multilateral development banks and their clients with future road safety
      initiatives, and to encourage better linkages between the health and
      transportation sectors supporting them. 

PMID- 24722741
TI  - Using baseline and formative evaluation data to inform the Uganda Helmet Vaccine
      Initiative.
AB  - Motorcycles are an important form of transportation in Uganda, and are involved
      in more road traffic injuries than any other vehicle. The majority of motorcycles
      in Uganda are used as motorcycle taxis, better known locally as boda bodas.
      Research shows that a motorcycle helmet is effective at reducing a rider's risk
      of death and head injury. As part of the Uganda Helmet Vaccine Initiative (UHVI),
      researchers collected baseline and formative evaluation data on boda boda
      operators' helmet attitudes, beliefs, and behaviors to inform UHVI activities.
      Researchers collected data on motorcycle helmet-related attitudes and beliefs
      through focus group discussions and structured roadside interviews, and
      researchers conducted roadside observations to collect data on helmet-wearing
      behaviors. Of the 12,189 motorcycle operators and passengers observed during
      roadside observations, 30.8% of drivers and <1% of passengers were wearing
      helmets. The most commonly reported helmet-wearing barriers from the focus group
      discussions and structured roadside interviews were: (1) 'Helmet is
      uncomfortable', (2) 'Helmet is too hot', (3) 'Helmet is too expensive', and (4)
      'Helmet is of low quality'. Researchers incorporated findings from the formative
      research into the UHVI campaign to increase motorcycle helmet use. Radio messages
      addressing helmet comfort and cost were widely aired throughout Kampala, Uganda.
      In addition, campaign staff held nine boda boda operator workshops, covering
      approximately 900 operators, in which the facilitator addressed barriers and
      facilitators to helmet use. Each workshop participant received a high-quality
      tropical motorcycle helmet. UHVI will continue to use a data-driven approach to
      future campaign activities. 

PMID- 24722742
TI  - Improving policy and practice to promote equity and social justice - a
      qualitative comparative analysis building on key learnings from a twinning
      exchange between England and the US.
AB  - Community health promotion interventions, targeted at marginalised populations
      and focusing on addressing the social determinants of health (SDH) to reduce
      health inequalities and addressing the processes of exclusion, are an important
      strategy to prevent and control non-communicable diseases (NCDs) and promote the
      health of underprivileged and under-resourced groups. This article builds on key
      lessons learnt from a learning exchange between Communities for Health in England
      and the Racial and Ethnic Approaches to Community Health across the US (REACH US)
      communities that are tackling health inequities. It presents a qualitative
      analysis further capturing information about specific community interventions
      involved in the exchange and identifying lessons learnt. This exchange was led by
      a partnership between the US Centers for Disease Control and Prevention, the
      International Union for Health Promotion and Education, the Department of Health
      of England, Health Action Partnership International, and Learning for Public
      Health West Midlands. These efforts provide interesting insights for further
      research, priority areas of action for policy and practice to address the SDH and
      to promote and sustain equity and social justice globally. The article highlights
      some key lessons about the use of data, assets-based community interventions and
      the importance of good leadership in times of crisis and adversity. Whilst
      complex and time-consuming to arrange, such programmes have the potential to
      offer other countries including the global south new insights and perspectives
      that will in turn contribute to the SDH field and provide concrete strategies and
      actions that effectively reduce inequities and promote the health of our
      societies. The key learnings have the potential to contribute to the global
      community and growing documentation on evidence of effective efforts in the
      reduction of health inequities. 

PMID- 24722743
TI  - Innovative approaches to promoting cervical health and raising cervical cancer
      awareness by use of existing cultural structures in resource-limited countries:
      experiences with traditional marriage counseling in Zambia.
AB  - The Cervical Cancer Prevention Program in Zambia (CCPPZ) has increasingly used
      community-level structures to increase the uptake and ensure the sustainability
      of the program. Traditional marriage counselors, the alangizi, who have existed
      in the Zambian society for many years, are one of the structures used by the
      program to impart cervical cancer knowledge and increase access to screening and
      care using an existing community structure. Several steps were followed in
      developing this intervention: (a) ensuring the alangizi understood the process of
      screening by encouraging them to go through the screening process; (b) workshops
      were arranged for the alangizi to meet and share experiences during which lessons
      were given on cervical cancer by health workers as well; and (c) eight alangizi
      were chosen to help document the lessons as part of ensuring that cervical cancer
      information is accurate and passed in a consistent manner. Over 70 alangizi, who
      had undergone cervical cancer screening, were trained by CCPPZ. A 'Cervical
      Cancer Training Manual for Marriage Counsellors' was developed to help the
      alangizi integrate cervical cancer lessons in their routine teachings. An
      evaluation was conducted during the training of the alangizi that forms the basis
      for this paper. The results show that although the alangizi face key challenges
      in their work (e.g. changing social contexts), they are still considered relevant
      by most communities in Zambia and are potentially an important avenue for
      cervical cancer and other health information. This paper shows that it is
      possible to integrate sexual and reproductive health messages into existing
      structures in the community. However, it is important to design culturally
      specific and sensitive healthcare strategies that embrace locally accepted good
      practices. 

PMID- 24722744
TI  - Physical activity, nutrition and behavior change in Latin America: a systematic
      review.
AB  - Physical activity (PA) and nutrition are key health behaviors underlying the
      design and implementation of prevention strategies for non-communicable diseases
      (NCDs) in Latin America. Nevertheless, research still reports low prevalence of
      PA and fruit and vegetable consumption throughout the region. This paper aims at
      reviewing the ways in which models of behavior change theory have been applied in
      study development and implementation regarding nutrition and PA in Latin America.
      In August 2011 we conducted a systematic literature review of the behavior change
      studies that targeted such NCDs risk factors published until then. Out of 4279
      surveyed abstracts, only 29 corresponded to articles that met our inclusion
      criteria. Twenty-six articles reported the application of behavior change theory,
      with the trans-theoretical model (n = 12) being the most frequently used. Other
      theories and models included the socio-ecological model (n = 4), cognitive theory
      (n = 3), social cognitive theory (n = 2) and theories related to health education
      and counseling (n = 5). Based on this review, we recommend that the application
      of behavior change theory be explicitly reported in Latin American peer-reviewed
      articles, and that outcome evaluations include behavior change constructs so as
      to better assess their contribution to the effectiveness of nutrition and PA
      interventions in the region. Furthermore, we state the need for a better
      understanding of the behavior change mechanisms that may be specific to the Latin
      American context. 

PMID- 24722745
TI  - A comparative study of perceptions on tobacco in vulnerable populations between
      India and France.
AB  - Perceptions of tobacco are a relatively unexplored issue in disadvantaged
      populations in India and France. The objectives of this study included the
      following: obtain qualitative information on representations of tobacco use and
      cessation within two vulnerable populations; identify cultural factors that
      influence tobacco use and cessation; and acquire information for the development
      of effective tobacco cessation strategies. A total of 21 focus groups were
      conducted in India and France. All study participants were disadvantaged adults
      18 years old or older. Sixty women resided in South Delhi in India and 163 adults
      with disabilities resided in the south of France. They were all current tobacco
      users. Data were collected by focus group and analysed with thematic coding. In
      both samples, the most relevant reasons of tobacco use were daily life
      circumstances, which were also a major barrier to quitting. None of the
      participants reported that quitting difficulties could be due to dependence or
      nicotine addiction. The data also suggested that whilst some participants wanted
      to stop, they also anticipated quitting would be extremely challenging. In
      addition, there were a number of cross-cultural differences between Indian and
      French disadvantaged people: level of information concerning the health risk
      related to tobacco use and level of demand for support to quit from health
      professionals were most often cited. Recommendations are made for a specific
      approach among disadvantaged people. The paper concludes that in order to
      facilitate cessation, tobacco control interventions need to focus on coping
      strategies to deal with feelings of distress, withdrawal symptoms, and the
      circumstances of everyday life experienced by disadvantaged tobacco users. 

PMID- 24722746
TI  - NCDs, health promotion and public health.
AB  - Though not necessarily using the same terminology historically, people concerned
      with the public's health have long been addressing the social context of non
      communicable diseases (NCDs) and the actions of promoting health. This commentary
      places the current interest in NCDs within that history and discusses the
      challenges that continue to face institutions in dealing with NCDs. It makes a
      particular plea for the role of health promotion as the area of public health
      that takes actions to address the global burden of NCDs. Without a health
      promotion focus, we will just continue to describe the NCD burden rather than
      reduce it. 

PMID- 24722747
TI  - Commentary on a meeting entitled 'Building global capacity for non-communicable
      diseases (NCD) prevention: Defining direction and roles'.
AB  - This Commentary summarizes the key points that arose during a three-day meeting
      held in Atlanta in July 2012 on Building Global Capacity for NCD Prevention. A
      wide spectrum of participants representing many sectors of global health,
      including ministries of health from several low and middle-income countries
      (LMICs), governmental institutions, non-governmental organizations, national
      disease associations, academia, and global and regional institutions
      participated. Presentations and group discussions led to agreement on a number of
      actions that should be taken to increase capacity for coping with NCDs in LMICs.
      Key areas of discussion were on the role of research, workforce development,
      resources, and governance. While there was considerable agreement on what should
      be done, the workshop participants had difficulty in prioritizing these
      activities. This led to an agreement by the gathered participants that a follow
      up Delphi study be conducted to help with prioritization. 

PMID- 24722748
TI  - The Consortium for NCD Prevention and Control in Sub-Saharan Africa (CNCD
      Africa): from concept to practice.
AB  - CNCD-Africa was established in July 2009 in response to and in recognition of the
      continuously increasing burden of diseases such as injuries, non-communicable
      diseases (NCDs) and mental health in low- and middle-income countries, and
      specifically in countries of sub-Saharan Africa. CNCD-Africa aims to
      comprehensively address specific and common objectives while building capacity in
      the region to prevent and control NCDs. With support from key partners and
      funders, and a keen interest in opportunities to address NCDs from health
      promotion and equity perspectives, the Consortium has excelled in four key areas:
      convening; knowledge generation and sharing; advocacy; and networking. However,
      the path to successful and sustainable efforts remains laden with challenges and
      barriers. Retaining interest of network partners through flagship efforts and
      continued efforts to ascertain support from local and international partners with
      interest in NCDs across the region remain essential to CNCD-Africa core
      activities. A key lesson learnt from the early years of CNCD-Africa is that
      existing regional platforms can and should be used to showcase what is being done
      locally, and to share best practices and best-buys. In addition, partnerships and
      stakeholder involvement have been key for CNCD-Africa and are essential to NCD
      action. Sustaining such partnerships requires incentives for the various partners
      to keep actively involved in NCD action. This can be achieved through joint
      inception, project planning, implementation, monitoring and evaluation. Another
      ingredient for success seems to be innovative financing for NCD efforts, which is
      possible through the establishment and sustaining of regional and global
      partnerships that are robust, locally relevant and respond to country needs. 

PMID- 24722749
TI  - Learning from communities in the USA and England to promote equity and address
      the social determinants of health.
AB  - This commentary contextualises and documents the process of a twinning learning
      exchange between the US Racial and Ethnic Approaches to Community Health
      initiative and the Communities for Health initiative in England to enable the
      transfer and adaptation of ideas for similar community-focused initiatives in
      various contexts globally. The multi-partner twinning exchange built on and
      shared knowledge around community health promotion interventions, targeting
      'marginalised' populations and focused on addressing the social determinants of
      health to effectively reduce health inequalities. This commentary presents the
      methodology of the exchange; provides key themes, outcomes and lessons learnt
      that arose from discussions and the experience; and provides insights,
      considerations and recommendations for adaptation. Finally, it highlights the
      importance of such exchanges in the current global context and the need for their
      replication and adaptation. These experiences contribute to building the evidence
      base on successful interventions and identifying strategies that work for
      improving health outcomes and reducing health inequalities. They strengthen the
      need for all governments to address the social determinants of health as a
      priority whilst providing insights to inform successful policy. 

PMID- 24722750
TI  - Global Advocacy for Physical Activity (GAPA): global leadership towards a raised
      profile.
AB  - Physical inactivity has been recognised by the World Health Organization as one
      of the leading causes of death due to non-communicable disease (NCD), worldwide.
      The benefits of action over inactivity can cut across health, environment,
      transportation, sport, culture and the economy. Despite the evidence, the
      policies and strategies to increase population-wide participation in physical
      activity receive insufficient priority from across high, middle and low-income
      countries; where physical inactivity is a rapidly-emerging issue. There is an
      increased need for all countries to invest in policies, strategies and supportive
      environments that inform, motivate and support individuals and communities to be
      active in ways that are safe, accessible and enjoyable. This commentary presents
      some recent efforts towards physical activity promotion globally, led by the
      Global Advocacy for Physical Activity (GAPA). It provides an overview of the
      background and history of GAPA; describes GAPA and the council's key achievements
      and milestones; places physical activity promotion within the global NCD agenda;
      presents GAPA flagships; and reflects on the lessons learned, ingredients for
      success and the major challenges that remain. The commentary documents insights
      into the effectiveness and challenges faced by a small non-governmental
      organisation (NGO) in mounting global advocacy. These lessons may be
      transferrable to other areas of health promotion advocacy. 

PMID- 24722751
TI  - Health-promoting schools: working in partnership to address global needs, a
      collaboration leading to the production of practical tools for practitioners.
AB  - Modern schools do their best to motivate young people to live fulfilling, healthy
      and productive lives and the United Nations has put school education at the heart
      of the Millennium Development Goals. The context of education in schools is
      changing, but there is evidence from across the world that school health
      promotion can make a difference to health and education outcomes. The
      International Union for Health Promotion and Education (IUHPE) has recognized
      this potential in schools and, for the last five years in its work globally, has
      been actively engaged in strengthening efforts through successful partnerships.
      This commentary explores aspects of global partnerships in school health and the
      progress of the IUHPE's leadership and partnership work in school health
      promotion. It also provides some reflections on what has been achieved to date
      and what might lie ahead in school health promotion globally. 

PMID- 24722754
TI  - Enhancement of mammographic density measures in breast cancer risk prediction.
AB  - BACKGROUND: Mammographic density is a strong risk factor for breast cancer.
      METHODS: We present a novel approach to enhance area density measures that takes
      advantage of the relative density of the pectoral muscle that appears in lateral
      mammographic views. We hypothesized that the grey scale of film mammograms is
      normalized to volume breast density but not pectoral density and thus pectoral
      density becomes an independent marker of volumetric density. RESULTS: From
      analysis of data from a Swedish case-control study (1,286 breast cancer cases and
      1,391 control subjects, ages 50-75 years), we found that the mean intensity of
      the pectoral muscle (MIP) was highly associated with breast cancer risk [per SD:
      OR = 0.82; 95% confidence interval (CI), 0.75-0.88; P = 6 * 10(-7)] after
      adjusting for a validated computer-assisted measure of percent density (PD),
      Cumulus. The area under curve (AUC) changed from 0.600 to 0.618 due to using PD
      with the pectoral muscle as reference instead of a standard area-based PD
      measure. We showed that MIP is associated with a genetic variant known to be
      associated with mammographic density and breast cancer risk, rs10995190, in a
      subset of women with genetic data. We further replicated the association between
      MIP and rs10995190 in an additional cohort of 2,655 breast cancer cases (combined
      P = 0.0002). CONCLUSIONS: MIP is a marker of volumetric density that can be used
      to complement area PD in mammographic density studies and breast cancer risk
      assessment. IMPACT: Inclusion of MIP in risk models should be considered for
      studies using area PD from analog films.

PMID- 24722755
TI  - The relationship between objectively measured physical activity, salivary
      cortisol, and the metabolic syndrome score in girls.
AB  - The relationship between physical activity levels, salivary cortisol, and the
      metabolic syndrome (MetSyn) score was examined. Twenty-three girls (8.4 +/- 0.9
      years) had a fasting blood draw, waist circumference and blood pressure measured,
      and wore an ActiGraph accelerometer for 5 days. Saliva samples were collected to
      measure cortisol levels. Previously established cut points estimated the minutes
      spent in moderate, vigorous, and moderate-to-vigorous physical activity. A
      continuous MetSyn score was created from blood pressure, waist circumference,
      high-density-lipoprotein (HDL), triglyceride, and glucose values. Correlation
      analyses examined associations between physical activity, cortisol, the MetSyn
      score, and its related components. Regression analysis examined the relationship
      between cortisol, the MetSyn score, and its related components adjusting for
      physical activity, percent body fat, and sexual maturity. Vigorous physical
      activity was positively related with 30 min post waking cortisol values. The
      MetSyn score was not related with cortisol values after controlling for
      confounders. In contrast, HDL was negatively related with 30 min post waking
      cortisol. Triglyceride was positively related with 30 min post waking cortisol
      and area under the curve. The MetSyn score and many of its components were not
      related to cortisol salivary levels even after adjusting for physical activity,
      body fat percentage, and sexual maturity. 

PMID- 24722756
TI  - Binding of glutathione to enterovirus capsids is essential for virion
      morphogenesis.
AB  - Enteroviruses (family of the Picornaviridae) cover a large group of medically
      important human pathogens for which no antiviral treatment is approved. Although
      these viruses have been extensively studied, some aspects of the viral life
      cycle, in particular morphogenesis, are yet poorly understood. We report the
      discovery of TP219 as a novel inhibitor of the replication of several
      enteroviruses, including coxsackievirus and poliovirus. We show that TP219 binds
      directly glutathione (GSH), thereby rapidly depleting intracellular GSH levels
      and that this interferes with virus morphogenesis without affecting viral RNA
      replication. The inhibitory effect on assembly was shown not to depend on an
      altered reducing environment. Using TP219, we show that GSH is an essential
      stabilizing cofactor during the transition of protomeric particles into
      pentameric particles. Sequential passaging of coxsackievirus B3 in the presence
      of low GSH-levels selected for GSH-independent mutants that harbored a surface
      exposed methionine in VP1 at the interface between two protomers. In line with
      this observation, enteroviruses that already contained this surface-exposed
      methionine, such as EV71, did not rely on GSH for virus morphogenesis.
      Biochemical and microscopical analysis provided strong evidence for a direct
      interaction between GSH and wildtype VP1 and a role for this interaction in
      localizing assembly intermediates to replication sites. Consistently, the
      interaction between GSH and mutant VP1 was abolished resulting in a
      relocalization of the assembly intermediates to replication sites independent
      from GSH. This study thus reveals GSH as a novel stabilizing host factor
      essential for the production of infectious enterovirus progeny and provides new
      insights into the poorly understood process of morphogenesis. 

PMID- 24722757
TI  - De novo transcriptome hybrid assembly and validation in the European earwig
      (Dermaptera, Forficula auricularia).
AB  - BACKGROUND: The European earwig (Forficula auricularia) is an established system
      for studies of sexual selection, social interactions and the evolution of
      parental care. Despite its scientific interest, little knowledge exists about the
      species at the genomic level, limiting the scope of molecular studies and
      expression analyses of genes of interest. To overcome these limitations, we
      sequenced and validated the transcriptome of the European earwig. METHODOLOGY AND
      PRINCIPAL FINDINGS: To obtain a comprehensive transcriptome, we sequenced mRNA
      from various tissues and developmental stages of female and male earwigs using
      Roche 454 pyrosequencing and Illumina HiSeq. The reads were de novo assembled
      independently and screened for possible microbial contamination and repeated
      elements. The remaining contigs were combined into a hybrid assembly and
      clustered to reduce redundancy. A comparison with the eukaryotic core gene
      dataset indicates that we sequenced a substantial part of the earwig
      transcriptome with a low level of fragmentation. In addition, a comparative
      analysis revealed that more than 8,800 contigs of the hybrid assembly show
      significant similarity to insect-specific proteins and those were assigned for
      Gene Ontology terms. Finally, we established a quantitative PCR test for
      expression stability using commonly used housekeeping genes and applied the
      method to five homologs of known sex-biased genes of the honeybee. The qPCR pilot
      study confirmed sex specific expression and also revealed significant expression
      differences between the brain and antenna tissue samples. CONCLUSIONS: By
      employing two different sequencing approaches and including samples obtained from
      different tissues, developmental stages, and sexes, we were able to assemble a
      comprehensive transcriptome of F. auricularia. The transcriptome presented here
      offers new opportunities to study the molecular bases and evolution of parental
      care and sociality in arthropods.

PMID- 24722759
TI  - Unusual coordination of tetrylenes to molybdenum carbonyl fragments.
AB  - Reactions of the tetrylenes Ge(SAr(Me6))2 (1) (Ar(Me6) = C6H3-2,6(C6H2-2,4,6
      Me3)2), and Sn(SAr(Me6))2 (2) with (Mo(CO)4(NBD) (NBD = bicyclo[2.2.1]hepta-2,5
      diene) gave three new, unusual complexes [Mo(THF)(CO)3{Ge(SAr(Me6))2}] (3),
      [Mo(THF)(CO)3{Ge(SAr(Me6))2}] (4) and [Mo(CO)4{Sn(SAr(Me6))2}] (5) which display
      no significant Ge/Sn-Mo bonding. Instead the ligands are coordinated to
      molybdenum in a bidentate fashion via the thiolato sulfurs.

PMID- 24722758
TI  - MicroRNA-143 targets Syndecan-1 to repress cell growth in melanoma.
AB  - Melanoma is the most aggressive type of skin cancer with a rapid progression and
      a limited efficiency of therapeutics. Recently, studies have identified some
      microRNAs playing important roles in the development of melanoma. Syndecan-1 (Syn
      1), dysregulated in many cancers, plays important roles in tumor progression by
      controlling cell proliferation. In this study, we investigated whether microRNA
      143 (miR-143) is involved in the regulation of Syn-1 and thus plays a functional
      role in melanoma. We found that miR-143 expression was significantly lower in
      melanoma tissues than in normal tissues and its low expression was closely
      related to clinical stages of melanoma. Further experiments showed that
      consistent with the inhibitory effects induced by knockdown of Syn-1,
      overexpression of miR-143 suppressed cell proliferation, promoted G1 phase arrest
      and induced apoptosis in melanoma. Downregulation of miR-143 apparently produced
      opposite effects. Combined treatment of miR-143 overexpression and Syn-1
      knockdown induced remarkable synergistic effects, while reconstitution of miR-143
      resistant Syn-1 reversed the inhibitory activity of miR-143. Moreover, miR-143
      level was inversely correlated with Syn-1 expression in melanoma cells. miR-143
      directly targeted the 3'-untranslated regions of Syn-1 mRNA and they were in the
      same Argonaute2 complex. Taken together, this study revealed a link between miRNA
      143 and Syn-1 in the pathogenesis of melanoma. MiR-143 plays an important role in
      the regulation of cell growth in melanoma. Restoration of miR-143 expression may
      represent a promising and efficient therapeutic approach for targeting malignant
      melanoma. 

PMID- 24722760
TI  - From laparoscopic to open Kasai portoenterostomy: the outcome after
      reintroduction of open Kasai portoenterostomy in infant with biliary atresia.
AB  - PURPOSE: Apparently superior result was observed after open Kasai
      portoenterostomy in infant with biliary atresia. Our institute stopped performing
      laparoscopic portoenterostomy since 2007. We aimed to investigate the outcome
      after reintroduction of open portoenterostomy. METHODS: 27 non-syndromic infants
      underwent open Kasai portoenterostomy from 2007 to 2012. The age and the sex of
      the patient, the bilirubin level before the operation, the early clearance of
      jaundice (total bilirubin <20 MUmol/L within 6 month of portoenterostomy), the
      native liver survival at 2 years after the operation were reviewed. The results
      were retrospectively compared with all 16 infants who underwent laparoscopic
      Kasai portoenterostomy before 2007. RESULTS: All infants had type III biliary
      atresia. No statistical difference was observed regarding the age at operation
      and the pre-operative bilirubin level. The early clearance of jaundice rate was
      81% (22/27) after open operation and was 50% (8/16) after laparoscopic operation
      (p = 0.03). At 2 years after the operation, the native liver survival was 81%
      (22/27) after open operation and was 50% (8/16) after laparoscopic operation (p =
      0.03). CONCLUSION: Reintroduction of open Kasai portoenterostomy was associated
      with superior early clearance of jaundice rate and 2-year native liver survival
      rate.

PMID- 24722761
TI  - Response from authors to comments on "An intervention for sensory difficulties in
      children with autism: a randomized trial".

PMID- 24722762
TI  - Brief report: functional MRI of a patient with 7q11.23 duplication syndrome and
      autism spectrum disorder.
AB  - The duplication of the Williams-Beuren syndrome (WBS) region (7q11.23) is a copy
      number variant associated with autism spectrum disorder (ASD). One of the most
      intriguing aspects is that the reciprocal microdeletion causes WBS, characterized
      by hypersociability, marked empathy, and a relative capacity in verbal short-term
      memory and language. Herein, we studied, by using functional morphological and
      volumetric magnetic resonance, a 17-year-old male patient who displays a de novo
      7q11.23 duplication and ASD. The limbic system of the patient appeared hypo
      functional, while the total brain volume was increased, thus contrasting, in an
      opposite and intriguing manner, with the global brain volume reduction reported
      in WBS. Even if these findings come from the analysis of a single patient and,
      therefore, have to be considered preliminary results, they encourage carrying on
      further functional and volumetric studies in patients with 7q11.23 duplication,
      to fully elucidate the role of this gene-dosage alteration on brain development
      and limbic system function. 

PMID- 24722763
TI  - Directed forgetting in high-functioning adults with autism spectrum disorders.
AB  - Rehearsal strategies of adults with autism spectrum disorders (ASDs) and
      demographically matched typically developed (TD) adults were strategically
      manipulated by cueing participants to either learn, or forget each list word
      prior to a recognition task. Participants were also asked to distinguish between
      autonoetic and noetic states of awareness using the Remember/Know paradigm. The
      ASD group recognised a similar number of to-be-forgotten words as the TD group,
      but significantly fewer to-be-learned words. This deficit was only evident in
      Remember responses that reflect autonoetic awareness, or episodic memory, and not
      Know responses. These findings support the elaborative encoding deficit
      hypothesis and provide a link between the previously established mild episodic
      memory impairments in adults with high functioning autism and the encoding
      strategies employed. 

PMID- 24722764
TI  - Efficiency enhancement of black dye-sensitized solar cells by newly synthesized D
      pi-A coadsorbents: a theoretical study.
AB  - In this work, using the DFT and TDDFT, we have theoretically studied the
      electronic and optical properties of the two recently synthesized coadsorbents Y1
      and Y2, which were aimed to enhance the efficiency of the black dye-sensitized
      solar cells. To determine the solvatochromic shifts, both the implicit and mixed
      implicit-explicit models have been used. The connection between the
      solvatochromic shifts and the changes in dipole moments in the excitation process
      is discussed. The difference in excitation charge transfer is utilized to explain
      the experimentally observed difference in Jsc for Y1 and Y2. Investigating the
      interactions of I2 molecules in the electrolyte solution with the coadsorbents
      showed that with Y1 the recombination loss was weakened through decreasing the I2
      concentration near the TiO2 surface, whereas with Y2 it was increased. As a
      result, the higher values of both Jsc and Voc with the Y1 coadsorbent explain its
      experimentally observed higher efficiency. The present study sheds light on how
      to design and engineer newer coadsorbents or organic dyes for higher
      efficiencies. 

PMID- 24722765
TI  - Protective factors and HIV risk behavior among South African men.
AB  - The primary mode of HIV transmission in South Africa is heterosexual sexual
      behavior. HIV prevention research specifically focusing on men in South Africa is
      limited. We assessed self-reported HIV risk behaviors in 1,181 men ages 18 to 45
      years in randomly selected neighborhoods in Eastern Cape Province, South Africa.
      Older men were less likely to report having multiple partners. Religiosity was a
      protective factor for condom use and unprotected sex with steady partners.
      Discussing using condoms was a protective factor for condom use and unprotected
      sex with both steady and casual partners. Having a child was associated with
      decreased condom use with steady partners and employment was associated with
      decreased condom use with casual partners. The findings suggest the need for HIV
      risk-reduction behavioral interventions tailored for South African men with
      regard to age, religiosity, and types of sexual partners. Implications for the
      development of such interventions are discussed.

PMID- 24722766
TI  - Electronegativity effects and single covalent bond lengths of molecules in the
      gas phase.
AB  - This paper discusses in detail the calculation of internuclear distances of
      heteronuclear single bond covalent molecules in the gaseous state. It reviews
      briefly the effect of electronegativity in covalent bond length. A set of single
      bond covalent radii and electronegativity values are proposed. Covalent bond
      lengths calculated by an adapted form of a simple expression (which calculated
      internuclear separation of different Group 1 and Group 2 crystalline salts to a
      remarkable degree of accuracy) show very good agreement with observed values. A
      small number of bond lengths with double bonds as well as bond lengths in the
      crystalline state are calculated using the same expression and when compared with
      observed values also give good agreement. This work shows that covalent radii are
      not additive and that radii in the crystalline state are different from those in
      the gaseous state. The results also show that electronegativity is a major
      influence on covalent bond lengths and the set of electronegativity scale and
      covalent radii proposed in this work can be used to calculate covalent bond
      lengths in different environments that have not yet been experimentally measured.

PMID- 24722768
TI  - Update in gastroenterology and hepatology: evidence published in 2013.

PMID- 24722767
TI  - Effects of sequential osteoporosis treatments on trabecular bone in adult rats
      with low bone mass.
AB  - We used an osteopenic adult ovariectomized (OVX) rat model to evaluate various
      sequential treatments for osteoporosis, using FDA-approved agents with
      complementary tissue-level mechanisms of action. Sequential treatment for 3
      months each with alendronate (Aln), followed by PTH, followed by resumption of
      Aln, created the highest trabecular bone mass, best microarchitecture, and
      highest bone strength. INTRODUCTION: Individual agents used to treat human
      osteoporosis reduce fracture risk by ~ 50-60%. As agents that act with
      complementary mechanisms are available, sequential therapies that mix
      antiresorptive and anabolic agents could improve fracture risk reduction, when
      compared with monotherapies. METHODS: We evaluated bone mass, bone
      microarchitecture, and bone strength in adult OVX, osteopenic rats, during
      different sequences of vehicle (Veh), parathyroid hormone (PTH), Aln, or
      raloxifene (Ral) in three 90-day treatment periods, over 9 months. Differences
      among groups were evaluated. The interrelationships of bone mass and
      microarchitecture endpoints and their relationship to bone strength were studied.
      RESULTS: Estrogen deficiency caused bone loss. OVX rats treated with Aln
      monotherapy had significantly better bone mass, microarchitecture, and bone
      strength than untreated OVX rats. Rats treated with an Aln drug holiday had bone
      mass and microarchitecture similar to the Aln monotherapy group but with
      significantly lower bone strength. PTH-treated rats had markedly higher bone
      endpoints, but all were lost after PTH withdrawal without follow-up treatment.
      Rats treated with PTH followed by Aln had better bone endpoints than those
      treated with Aln monotherapy, PTH monotherapy, or an Aln holiday. Rats treated
      initially with Aln or Ral, then switched to PTH, also had better bone endpoints,
      than monotherapy treatment. Rats treated with Aln, then PTH, and returned to Aln
      had the highest values for all endpoints. CONCLUSION: Our data indicate that
      antiresorptive therapy can be coupled with an anabolic agent, to produce and
      maintain better bone mass, microarchitecture, and strength than can be achieved
      with any monotherapy.

PMID- 24722769
TI  - Intensive nutrition in acute lung injury: a clinical trial (INTACT).
AB  - BACKGROUND: Despite extensive use of enteral (EN) and parenteral nutrition (PN)
      in intensive care unit (ICU) populations for 4 decades, evidence to support their
      efficacy is extremely limited. METHODS: A prospective randomized trial was
      conducted evaluate the impact on outcomes of intensive medical nutrition therapy
      (IMNT; provision of >75% of estimated energy and protein needs per day via EN and
      adequate oral diet) from diagnosis of acute lung injury (ALI) to hospital
      discharge compared with standard nutrition support care (SNSC; standard EN and ad
      lib feeding). The primary outcome was infections; secondary outcomes included
      number of days on mechanical ventilation, in the ICU, and in the hospital and
      mortality. RESULTS: Overall, 78 patients (40 IMNT and 38 SNSC) were recruited. No
      significant differences between groups for age, body mass index, disease
      severity, white blood cell count, glucose, C-reactive protein, energy or protein
      needs occurred. The IMNT group received significantly higher percentage of
      estimated energy (84.7% vs 55.4%, P < .0001) and protein needs (76.1 vs 54.4%, P
      < .0001) per day compared with SNSC. No differences occurred in length of
      mechanical ventilation, hospital or ICU stay, or infections. The trial was
      stopped early because of significantly greater hospital mortality in IMNT vs SNSC
      (40% vs 16%, P = .02). Cox proportional hazards models indicated the hazard of
      death in the IMNT group was 5.67 times higher (P = .001) than in the SNSC group.
      CONCLUSIONS: Provision of IMNT from ALI diagnosis to hospital discharge increases
      mortality.

PMID- 24722770
TI  - A pediatric correlational study of stride interval dynamics, energy expenditure
      and activity level.
AB  - The strength of time-dependent correlations known as stride interval (SI)
      dynamics has been proposed as an indicator of neurologically healthy gait. Most
      recently, it has been hypothesized that these dynamics may be necessary for gait
      efficiency although the supporting evidence to date is scant. The current study
      examines over-ground SI dynamics, and their relationship with the cost of walking
      and physical activity levels in neurologically healthy children aged nine to 15
      years. Twenty participants completed a single experimental session consisting of
      three phases: 10 min resting, 15 min walking and 10 min recovery. The scaling
      exponent (alpha) was used to characterize SI dynamics while net energy cost was
      measured using a portable metabolic cart, and physical activity levels were
      determined based on a 7-day recall questionnaire. No significant linear
      relationships were found between a and the net energy cost measures (r < .07; p >
      .25) or between alpha and physical activity levels (r = .01, p = .62). However,
      there was a marked reduction in the variance of alpha as activity levels
      increased. Over-ground stride dynamics do not appear to directly reflect energy
      conservation of gait in neurologically healthy youth. However, the reduction in
      the variance of alpha with increasing physical activity suggests a potential
      exercise-moderated convergence toward a level of stride interval persistence for
      able-bodied youth reported in the literature. This latter finding warrants
      further investigation. 

PMID- 24722771
TI  - Postnatal Erythropoietin Mitigates Impaired Cerebral Cortical Development
      Following Subplate Loss from Prenatal Hypoxia-Ischemia.
AB  - Preterm birth impacts brain development and leads to chronic deficits including
      cognitive delay, behavioral problems, and epilepsy. Premature loss of the
      subplate, a transient subcortical layer that guides development of the cerebral
      cortex and axonal refinement, has been implicated in these neurological
      disorders. Subplate neurons influence postnatal upregulation of the potassium
      chloride co-transporter KCC2 and maturation of gamma-amino-butyric acid A
      receptor (GABAAR) subunits. We hypothesized that prenatal transient systemic
      hypoxia-ischemia (TSHI) in Sprague-Dawley rats that mimic brain injury from
      extreme prematurity in humans would cause premature subplate loss and affect
      cortical layer IV development. Further, we predicted that the neuroprotective
      agent erythropoietin (EPO) could attenuate the injury. Prenatal TSHI induced
      subplate neuronal loss via apoptosis. TSHI impaired cortical layer IV postnatal
      upregulation of KCC2 and GABAAR subunits, and postnatal EPO treatment mitigated
      the loss (n >= 8). To specifically address how subplate loss affects cortical
      development, we used in vitro mechanical subplate ablation in slice cultures (n
      >= 3) and found EPO treatment attenuates KCC2 loss. Together, these results show
      that subplate loss contributes to impaired cerebral development, and EPO
      treatment diminishes the damage. Limitation of premature subplate loss and the
      resultant impaired cortical development may minimize cerebral deficits suffered
      by extremely preterm infants. 

PMID- 24722772
TI  - Low-dose formaldehyde delays DNA damage recognition and DNA excision repair in
      human cells.
AB  - OBJECTIVE: Formaldehyde is still widely employed as a universal crosslinking
      agent, preservative and disinfectant, despite its proven carcinogenicity in
      occupationally exposed workers. Therefore, it is of paramount importance to
      understand the possible impact of low-dose formaldehyde exposures in the general
      population. Due to the concomitant occurrence of multiple indoor and outdoor
      toxicants, we tested how formaldehyde, at micromolar concentrations, interferes
      with general DNA damage recognition and excision processes that remove some of
      the most frequently inflicted DNA lesions. METHODOLOGY/PRINCIPAL FINDINGS: The
      overall mobility of the DNA damage sensors UV-DDB (ultraviolet-damaged DNA
      binding) and XPC (xeroderma pigmentosum group C) was analyzed by assessing real
      time protein dynamics in the nucleus of cultured human cells exposed to non
      cytotoxic (<100 MUM) formaldehyde concentrations. The DNA lesion-specific
      recruitment of these damage sensors was tested by monitoring their accumulation
      at local irradiation spots. DNA repair activity was determined in host-cell
      reactivation assays and, more directly, by measuring the excision of DNA lesions
      from chromosomes. Taken together, these assays demonstrated that formaldehyde
      obstructs the rapid nuclear trafficking of DNA damage sensors and, consequently,
      slows down their relocation to DNA damage sites thus delaying the excision repair
      of target lesions. A concentration-dependent effect relationship established a
      threshold concentration of as low as 25 micromolar for the inhibition of DNA
      excision repair. CONCLUSIONS/SIGNIFICANCE: A main implication of the retarded
      repair activity is that low-dose formaldehyde may exert an adjuvant role in
      carcinogenesis by impeding the excision of multiple mutagenic base lesions. In
      view of this generally disruptive effect on DNA repair, we propose that
      formaldehyde exposures in the general population should be further decreased to
      help reducing cancer risks.

PMID- 24722773
TI  - Coxsackievirus B exits the host cell in shed microvesicles displaying
      autophagosomal markers.
AB  - Coxsackievirus B3 (CVB3), a member of the picornavirus family and enterovirus
      genus, causes viral myocarditis, aseptic meningitis, and pancreatitis in humans.
      We genetically engineered a unique molecular marker, "fluorescent timer" protein,
      within our infectious CVB3 clone and isolated a high-titer recombinant viral
      stock (Timer-CVB3) following transfection in HeLa cells. "Fluorescent timer"
      protein undergoes slow conversion of fluorescence from green to red over time,
      and Timer-CVB3 can be utilized to track virus infection and dissemination in real
      time. Upon infection with Timer-CVB3, HeLa cells, neural progenitor and stem
      cells (NPSCs), and C2C12 myoblast cells slowly changed fluorescence from green to
      red over 72 hours as determined by fluorescence microscopy or flow cytometric
      analysis. The conversion of "fluorescent timer" protein in HeLa cells infected
      with Timer-CVB3 could be interrupted by fixation, suggesting that the fluorophore
      was stabilized by formaldehyde cross-linking reactions. Induction of a type I
      interferon response or ribavirin treatment reduced the progression of cell-to
      cell virus spread in HeLa cells or NPSCs infected with Timer-CVB3. Time lapse
      photography of partially differentiated NPSCs infected with Timer-CVB3 revealed
      substantial intracellular membrane remodeling and the assembly of discrete virus
      replication organelles which changed fluorescence color in an asynchronous
      fashion within the cell. "Fluorescent timer" protein colocalized closely with
      viral 3A protein within virus replication organelles. Intriguingly, infection of
      partially differentiated NPSCs or C2C12 myoblast cells induced the release of
      abundant extracellular microvesicles (EMVs) containing matured "fluorescent
      timer" protein and infectious virus representing a novel route of virus
      dissemination. CVB3 virions were readily observed within purified EMVs by
      transmission electron microscopy, and infectious virus was identified within low
      density isopycnic iodixanol gradient fractions consistent with membrane
      association. The preferential detection of the lipidated form of LC3 protein (LC3
      II) in released EMVs harboring infectious virus suggests that the autophagy
      pathway plays a crucial role in microvesicle shedding and virus release, similar
      to a process previously described as autophagosome-mediated exit without lysis
      (AWOL) observed during poliovirus replication. Through the use of this novel
      recombinant virus which provides more dynamic information from static fluorescent
      images, we hope to gain a better understanding of CVB3 tropism, intracellular
      membrane reorganization, and virus-associated microvesicle dissemination within
      the host. 

PMID- 24722774
TI  - Hip structural parameters over 96 weeks in HIV-infected adults switching
      treatment to tenofovir-emtricitabine or abacavir-lamivudine.
AB  - BACKGROUND: Therapy with tenofovir is associated with lower bone mineral density
      (BMD), higher markers of bone turnover and increased fracture risk in HIV
      infected adults. Bone structural parameters generated by hip structural analysis
      may represent a separate measure of bone strength, but have not been assessed in
      HIV. METHODS: Dual-energy X-ray absorptiometry (DXA) scans from 254 HIV-infected
      adults randomised to simplify their existing dual nucleoside analogue reverse
      transcriptase inhibitor therapy to coformulated tenofovir-emtricitabine or
      abacavir-lamivudine were analysed using DXA-derived hip structural analysis
      software. Hip structural parameters included femoral strength index, section
      modulus, cross-sectional area, and cross-sectional moment of inertia. We used one
      way ANOVA to test the relationship between nucleoside analogue type at baseline
      and structural parameters, multivariable analysis to assess baseline covariates
      associated with femoral strength index, and t-tests to compare mean change in
      structural parameters over 96 weeks between randomised groups. RESULTS:
      Participants taking tenofovir at baseline had lower section modulus (-107.3 mm2,
      p = 0.001), lower cross-sectional area (-15.01 mm3, p = 0.001), and lower cross
      sectional moment of inertia (-2,036.8 mm4, p = 0.007) than those receiving other
      nucleoside analogues. After adjustment for baseline risk factors, the association
      remained significant for section modulus (p = 0.008) and cross-sectional area (p
      = 0.002). Baseline covariates significantly associated with higher femoral
      strength index were higher spine T-score (p = 0.001), lower body fat mass
      (p<0.001), lower bone alkaline phosphatase (p = 0.025), and higher
      osteoprotegerin (p = 0.024). Hip structural parameters did not change
      significantly over 96 weeks and none was significantly affected by treatment
      simplification to tenofovir-emtricitabine or abacavir-lamivudine. CONCLUSION: In
      this population, tenofovir use was associated with reduced composite indices of
      bone strength as measured by hip structural analysis, but none of the structural
      parameters improved significantly over 96 weeks with tenofovir cessation. TRIAL
      REGISTRATION: ClinicalTrials.gov NCT00192634.

PMID- 24722775
TI  - Low-level laser therapy prevents degenerative morphological changes in an
      experimental model of anterior cruciate ligament transection in rats.
AB  - The aim of this study was to analyze the effects of low-level laser therapy
      (LLLT) on the prevention of cartilage damage after the anterior cruciate ligament
      transection (ACLT) in knees of rats. Thirty male rats (Wistar) were distributed
      into three groups (n = 10 each): injured control group (CG); injured laser
      treated group at 10 J/cm(2) (L10), and injured laser-treated group at 50 J/cm(2)
      (L50). Laser treatment started immediately after the surgery and it was performed
      for 15 sessions. An 808 nm laser, at 10 and 50 J/cm(2), was used. To evaluate the
      effects of LLLT, the qualitative and semi-quantitative histological,
      morphometric, and immunohistochemistry analysis were performed. Initial signs of
      tissue degradation were observed in CG. Interestingly, laser-treated animals
      presented a better tissue organization, especially at the fluence of 10 J/cm(2).
      Furthermore, laser phototherapy was able of modulating some of the aspects
      related to the degenerative process, such as the prevention of proteoglycans loss
      and the increase in cartilage area. However, LLLT was not able of modulating
      chondrocytes proliferation and the immunoexpression of markers related to
      inflammatory process (IL-1 and MMP-13). This study showed that 808 nm laser, at
      both fluences, prevented features related to the articular degenerative process
      in the knees of rats after ACLT.

PMID- 24722777
TI  - Living independently as an ethnic minority elder: a relational perspective on the
      issues of aging and ethnic minorities.
AB  - This study examines the residential experiences of Korean ethnic elders in
      affordable housing in the greater Chicago area, focusing on how patterns of
      social relationships that evolved around a geographical location and its urban
      infrastructure enabled the elders to achieve their desire for residential
      independence. Based on the theoretical concept of activity settings and social
      capital, the study suggests an integrated theoretical model where social capital
      is understood as an embedded asset of an activity setting. Methodologically, this
      study uses a combined method of qualitative interviews with 138 Korean elders in
      affordable housing in the greater Chicago area and a geographic analysis of their
      social relationships in order to present associations among social relationships,
      urban infrastructures, and the shared value of independence within their
      residential communities. The study findings indicate that the elders mobilized
      ethnic businesses, urban infrastructures, and the collective efficacy of groups
      to achieve the shared goal of maintaining residential independence. In each
      community, a cultural broker acted as an important bridge between the community
      of ethnic minorities and the larger social networks coexisting within the
      community boundary. The relational perspective as a potent ground for
      understanding and further solving the issues of aging and ethnicity is
      highlighted. 

PMID- 24722776
TI  - Species-specific expansion and molecular evolution of the 3-hydroxy-3
      methylglutaryl coenzyme A reductase (HMGR) gene family in plants.
AB  - The terpene compounds represent the largest and most diverse class of plant
      secondary metabolites which are important in plant growth and development. The 3
      hydroxy-3-methylglutaryl coenzyme A reductase (HMGR; EC 1.1.1.34) is one of the
      key enzymes contributed to terpene biosynthesis. To better understand the basic
      characteristics and evolutionary history of the HMGR gene family in plants, a
      genome-wide analysis of HMGR genes from 20 representative species was carried
      out. A total of 56 HMGR genes in the 14 land plant genomes were identified, but
      no genes were found in all 6 algal genomes. The gene structure and protein
      architecture of all plant HMGR genes were highly conserved. The phylogenetic
      analysis revealed that the plant HMGRs were derived from one ancestor gene and
      finally developed into four distinct groups, two in the monocot plants and two in
      dicot plants. Species-specific gene duplications, caused mainly by segmental
      duplication, led to the limited expansion of HMGR genes in Zea mays, Gossypium
      raimondii, Populus trichocarpa and Glycine max after the species diverged. The
      analysis of Ka/Ks ratios and expression profiles indicated that functional
      divergence after the gene duplications was restricted. The results suggested that
      the function and evolution of HMGR gene family were dramatically conserved
      throughout the plant kingdom. 

PMID- 24722778
TI  - A novel microfluidic approach for preparing chitosan-silica core-shell hybrid
      microspheres with controlled structures and their catalytic performance.
AB  - A facile microfluidic approach to prepare chitosan-silica core-shell hybrid
      microspheres with different pore structures has been developed. The hybrid
      microspheres showed good performance in mechanics and adsorption and are
      outstanding and green catalyst supports. Under optimum conditions, the adsorption
      capacity of Cu(ii) is about 1.7 times that of chitosan-silica hybrid microspheres
      with uniform component distribution for the effective protection of -NH2 provided
      by the silica shell while the mechanical intensity is about 2 times that of
      porous chitosan microspheres. Furthermore, when the adsorbed Cu(ii) is reduced to
      Cu(i), the chitosan-silica supported Cu(i) will be an outstanding catalyst for
      azide-alkyne cycloaddition reaction and the reaction can complete in water within
      3 h at room temperature. The catalyst was easy to be recovered just through
      sedimentation by gravity or filtration. Further, the chitosan-silica supported
      catalyst can be reused many times without losing its activity and it can be
      reproducible when the catalytic activity decreases. The whole process is green,
      environmentally friendly and atom economic. 

PMID- 24722779
TI  - Assessing patient-caregiver communication in cancer--a psychometric validation of
      the Cancer Communication Assessment Tool (CCAT-PF) in a German sample.
AB  - PURPOSE: The recently introduced Cancer Communication Assessment Tool (CCAT-PF)
      measures congruence in patient-caregiver communication and was initially
      validated in lung cancer patients. Contributing to a greater proportion of the
      variance in the conflict scores, primary caregivers were hypothesized to
      experience greater stress. For a detailed understanding of conflicting
      communication patterns of cancer-affected families, our study aimed for
      psychometric validation of the CCAT-PF in a sample covering heterogeneous tumor
      entities. METHODS: Subsequent to a cross-sectional survey of 189 pairs of cancer
      patients (31 % gastrointestinal, 34 % lung, and 35 % urological) and their
      caregivers' exploratory factor analysis with principal component condensation and
      varimax rotation was conducted (response rate, 74.2 %). Reliability and construct
      validity were assessed calculating Cronbach's alpha and Pearson correlation
      coefficients for CCAT-P and CCAT-F scales and related constructs, respectively.
      RESULTS: Cancer-related communication according to the CCAT-PF can be subdivided
      into four factors including the scales Disclosure, Limitation of treatment,
      Family involvement in treatment decisions, and Continuing treatment. Reliability
      ranged from alpha = .51-.68. The Disclosure scale, describing poor cancer-related
      communication of the patient, was correlated with patient's distress (QSC-R10: r
      = .30, p < .0001), unmet needs in several areas (SCNS-SF-34: r = .25-.32, p <
      .001), and negatively with social/family well-being (FACT: r = -0.31, p < .0001).
      Higher scores on the scale were significantly associated with considerable
      decrements in emotional well-being especially for caregivers perceiving patients'
      disclosure as problematic. CONCLUSIONS: The Disclosure scale originating from the
      CCAT-PF emerged as a short, valid, and reliable stand-alone instrument for
      identifying conflicting communication in patient-caregiver-dyads at risk.

PMID- 24722780
TI  - Reoperation for post-hepatectomy hemorrhage: increased risk of mortality.
AB  - BACKGROUND: Reoperation for post-hepatectomy hemorrhage (PHH) represents an
      important complication in patients undergoing liver resection. Yet, few studies
      have reported its presentation and patient outcomes of this event. METHODS: Among
      the 2,086 patients who underwent elective hepatectomy from 2000 to 2009 in our
      HPB unit, the perioperative data of 12 (0.6 %) patients who underwent re
      laparotomy for PHH were retrospectively analyzed. RESULTS: The diagnosis of PHH
      was established in all cases by the presence of blood in the drain. The mean
      interval time between the end of liver resection and the diagnosis of bleeding
      and reoperation were 17 h (1-43) and 38 h (1-93), respectively. The causes of
      bleeding were the hepatic vein branch (n = 4), liver cut surface (n = 3), and a
      hepatic artery branch (n = 2). In three cases, no bleeding spot was identified.
      Postoperative death occurred in 3 patients (25 %) between 15 and 18 days after re
      laparotomy. These 3 patients were all cirrhotic; 2 underwent early re-laparotomy
      (<=6 h) and 1 underwent re-laparotomy 24 h after the first recognition of active
      bleeding. CONCLUSION: Reoperation for PHH remains an important morbid event after
      liver resection. Death in patients with this complication is considerably high.
      It is diagnosed mainly on the aspect of the abdominal drain, justifying its use
      in risky patients.

PMID- 24722781
TI  - The impact of abdominal complications on the outcome after thoracic
      transplantation--a single center experience.
AB  - BACKGROUND: Abdominal complications after thoracic transplantation (Tx) are
      potentially associated with an increased risk of mortality. We recently reported
      about the severe outcome after bowel perforation in patients following lung
      transplantation (LuTx). The aim of the present study was to likewise identify the
      risk factors with an impact on patient survival following heart transplantation
      (HTx). METHODS: A retrospective analysis for the frequency and outcome of
      abdominal interventions following HTx was performed in 342 patients, and these
      data thereafter compared to a re-evaluated pool of 1,074 patients following LuTx.
      All patients were transplanted at Hanover Medical School, Germany, between
      January 2000 and October 2011. RESULTS: The incidence for abdominal surgery was
      comparable between patients following HTx (n = 33; 9.6 %) and LuTx (n = 90; 8.4
      %). Elective operations were more frequently performed in patients after HTx (8.5
      vs. 5.1 %). In contrast, the incidence of emergency interventions was higher
      after LuTx (5.3 %) than that following HTx (2.3 %). Herewith associated was the
      mortality observed in these transplant recipients (15.3 and 9.9 % for LuTx and
      HTx, respectively). Leading diagnosis for emergency surgery was bowel perforation
      (n = 18, regarding all cases). In 11 of these patients, perforation occurred
      within the first 6 months after Tx and eight of them died in the course of this
      complication (one patient after HTx and seven patients after LuTx). CONCLUSIONS:
      Abdominal complications after HTx are less frequently than after LuTx but equally
      correlate with a high mortality rate. In finding or even reasonable suspicion of
      an acute abdomen after thoracic Tx, a broad practice for extended diagnostics and
      a low barrier for an early explorative laparotomy thus are recommended.

PMID- 24722782
TI  - CB2 receptor deficiency increases amyloid pathology and alters tau processing in
      a transgenic mouse model of Alzheimer's disease.
AB  - The endocannabinoid CB2 receptor system has been implicated in the neuropathology
      of Alzheimer's disease (AD). In order to investigate the impact of the CB2
      receptor system on AD pathology, a colony of mice with a deleted CB2 receptor
      gene, CNR2, was established on a transgenic human mutant APP background for
      pathological comparison with CB2 receptor-sufficient transgenic mice. J20 APP
      (PDGFB-APPSwInd) mice were bred over two generations with CNR2(-/-)
      (Cnr2(tm1Dgen)/J) mice to produce a colony of J20 CNR2(+/+) and J20 CNR2(-/-)
      mice. Seventeen J20 CNR2(+/+) mice (12 females, 5 males) and 16 J20 CNR2(-/-)
      mice (11 females, 5 males) were killed at 12 months, and their brains were
      interrogated for AD-related pathology with both biochemistry and
      immunocytochemistry (ICC). In addition to amyloid-dependent endpoints such as
      soluble Abeta production and plaque deposition quantified with 6E10 staining, the
      effect of CB2 receptor deletion on total soluble mouse tau production was assayed
      by using a recently developed high-sensitivity assay. Results revealed that
      soluble Abeta42 and plaque deposition were significantly increased in J20 CNR2(-/
      ) mice relative to CNR2(+/+) mice. Microgliosis, quantified with ionized calcium
      binding adapter molecule 1 (Iba-1) staining, did not differ between groups,
      whereas plaque associated microglia was more abundant in J20 CNR2(-/-) mice.
      Total tau was significantly suppressed in J20 CNR2(-/-) mice relative to J20
      CNR2(+/+) mice. The results confirm the constitutive role of the CB2 receptor
      system both in reducing amyloid plaque pathology in AD and also support
      tehpotential of cannabinoid therapies targeting CB2 to reduce Abeta; however, the
      results suggest that interventions may have a divergent effect on tau pathology. 

PMID- 24722784
TI  - Internists' attitudes toward prevention of firearm injury.
AB  - BACKGROUND: Professional organizations have called for the medical community's
      attention to the prevention of firearm injury. However, little is known about
      physicians' attitudes and practices in preventing firearm injury. OBJECTIVE: To
      determine internists' attitudes and practices about firearms and to assess
      whether opinions differ according to whether there are gun owners in a
      physician's home. DESIGN: Cross-sectional survey. SETTING: Internal medicine
      practices. PARTICIPANTS: 573 internists representative of American College of
      Physicians' members. MEASURES: Respondents' experiences and reported practice
      behaviors related to firearms and their opinions about contributors and public
      policies related to firearm violence, as well as physician education and training
      in firearm safety. RESULTS: The survey response rate was 56.5%. Eighty-five
      percent of respondents believed that firearm injury is a public health issue, and
      71% believed that it is a bigger problem today than a decade ago. Seventy-six
      percent of respondents believed that stricter gun control legislation would help
      reduce the risks for gun-related injuries or deaths. Although 66% of respondents
      believed that physicians should have the right to counsel patients on preventing
      deaths and injuries from firearms, 58% reported never asking whether patients
      have guns in their homes. LIMITATIONS: The generalizability of these findings to
      non-American College of Physicians' member internists and other physicians is
      unknown. Responses may not reflect actual behavior. CONCLUSION: Most respondents
      believed that firearm-related violence is a public health issue and favored
      policy initiatives aimed at reducing it. Although most internists supported a
      physician's right to counsel patients about gun safety, few reported currently
      doing it. PRIMARY FUNDING SOURCE: None.

PMID- 24722786
TI  - Reply to letter to editor: patient-specific instruments in total knee
      arthroplasty.

PMID- 24722785
TI  - The safety and efficacy of minimally invasive discectomy: a meta-analysis of
      prospective randomised controlled trials.
AB  - PURPOSE: The objective of this study was to compare the safety and efficacy of
      minimally invasive discectomy (MID) with standard discectomy (SD) and determine
      whether the use of the MID technique could decrease the recurrence of lumbar disc
      herniation (LDH) after the surgery. METHODS: In February 2014, a comprehensive
      search was performed in PubMed, EMBASE, Web of Science, Cochrane Library and the
      Chinese Biological Medicine Database. Only randomised controlled trials (RCT)
      that compared MID with SD for the surgical management of LDH were included. These
      trials were carefully picked out following the inclusion and exclusion criteria.
      Using the Cochrane Collaboration guidelines, two authors independently extracted
      data and assessed these trials' quality. The age of the patients, size of
      incision, surgical time, blood loss, visual analogue scale (VAS) score after the
      surgery, hospital stay, disc herniation recurrence, X-ray exposure and surgical
      costs in these studies were abstracted and synthesised by a meta-analysis with
      RevMan 5.2.0 software, and the main results (VAS score after the surgery and disc
      herniation recurrence) of publication bias were examined by Stata 12.0. RESULTS:
      Overall, 16 trials involving 2,139 patients meeting our criteria were included
      and analysed. Comparing MID and SD, the former was more likely to increase disc
      herniation recurrence [relative risk (RR) = 1.95, 95 % confidence interval (CI)
      1.19-3.19, p = 0.008], and it involved a smaller size of incision [mean
      difference (MD) = -1.91, 95 % CI -3.33 to -0.50, p = 0.008], shorter hospital
      stay, longer operating time (MD = 11.03, 95 %C I 6.62-15.44, p < 0.00001) and
      less blood loss (MD = -13.56, 95 % CI -22.26 to -4.87, p = 0.002), while no
      statistical difference appeared with regard to the age of the patients, VAS score
      after the surgery, X-ray exposure, hospital stay and surgical costs. CONCLUSIONS:
      Based on available evidence, MID results in less suffering for patients during
      the hospital course with a similar clinical efficacy compared to SD. This makes
      MID a promising procedure for patients with LDH; however, to popularise it
      greater effort is required to reduce disc herniation recurrence.

PMID- 24722787
TI  - Targeted pre-operative autologous blood donation: a prospective study of two
      thousand and three hundred and fifty total hip arthroplasties.
AB  - PURPOSE: Pre-operative donation of autologous blood has been widely used in
      elective joint replacement procedures to avoid the risks of allogeneic blood
      transfusions. However, the high percentage of wasted autologous blood questions
      the general efficacy of pre-operative autologous blood donation (PABD) for all
      patients undergoing hip replacement. This study prospectively investigates the
      impact of a targeted pre-operative autologous blood donation protocol for anaemic
      patients on allogeneic and overall transfusion rates in 2,350 unilateral primary
      total hip arthroplasty procedures. METHODS: Patients with pre-operative
      haemoglobin less than 12.5 g/dL were advised to donate one unit of autologous
      blood seven to 15 days prior to the date of surgery. The targeted protocol was
      followed by 2,251 patients: 280 out of 367 anaemic patients donated while 1,971
      out of 1,983 non-anaemic patients did not donate. RESULTS: Results showed a
      significantly lower rate of allogeneic transfusion for anaemic patients who
      predonated than anaemic patients who did not (13 % vs. 37% respectively, p <
      0.001). Overall transfusion rates for patients who followed the protocol (n =
      2,251) were found to be 0.17 units/patient compared to previously reported
      numbers of 0.75 units/patient when routine donation was used. Among the 2,251
      patients who followed the protocol, only 140 patients (6%) had their autologous
      blood wasted, in contrast to values reported in the literature ranging from 14%
      up to 50%. CONCLUSIONS: Targeted PABD reduces the need for allogeneic blood
      transfusion in anaemic patients and significantly reduces the overall number of
      transfusions compared to routine pre-operative autologous donation.

PMID- 24722788
TI  - Opening wedge high tibial osteotomy: navigation system compared to the
      conventional technique in a controlled clinical study.
AB  - PURPOSE: This study aimed to verify if the navigation system used in high tibial
      osteotomy (HTO) adds precision to the procedure regarding mechanical axis
      correction and prevention of tibial slope increases. METHODS: In this
      historically controlled study, patients with medial osteoarthrosis and genuvarum
      underwent HTO between 2004 and 2012; the first 20 were operated with the
      conventional technique, using pre-planning correction by the Dugdale method and
      18 further patients were operated with the navigation system introduced in our
      hospital. RESULTS: The two groups were similar for pre-operative mechanical axis
      (mean 8.10 +/- 3.14 for the control and 6.60 +/- 2.50 for the navigated group),
      pre-operative tibial slope (mean 8.95 +/- 3.47 versus 8.17 +/- 3.11,
      respectively) and Lyshom score (40.85 +/- 15.46 and 44.83 +/- 16.86). After
      surgery, the control group presented mean mechanical axis of 3.35 +/- 3.27,
      tibial slope of 13.75 +/- 3.75 and Lyshom score of 87.60 +/- 11.12. The navigated
      group showed a postoperative mechanical axis mean of 3.06 +/- 1.70, tibial slope
      of 10.11 +/- 0.18 and Lyshom score of 91.94 +/- 11.61. CONCLUSIONS: The
      navigation system allowed a significantly better control of tibial slope.
      Patients operated with the navigation system had significantly better Lysholm
      scores.

PMID- 24722789
TI  - The incidence of monozygotic twinning in assisted reproductive technology:
      analysis based on results from the 2010 Japanese ART national registry.
AB  - PURPOSE: To assess the incidence of monozygotic twinning (MZT) among cases
      undergoing assisted reproductive technology (ART) treatment. METHODS: We
      performed a retrospective observational study and analyzed the data of patients
      who were registered in the national ART registry system of Japan from January to
      December 2010; only the data of patients with single embryo transfer (ET) were
      included. RESULTS: Of 30,405 pregnancies, 425 resulted in MZT following fresh and
      frozenthawed ET. The MZT incidence among women undergoing ART was 1.4 %. Multiple
      logistic regression analysis indicated that cases undergoing fresh and frozen
      thawed ET, blastocyst transfer had a significantly increased MZT rate (P < 0.01).
      Assisted hatching (AH) and frozen-thawed ET and maternal age did not
      significantly affect the MZT incidence. Of 8510 fresh ET pregnancies, 104
      resulted in MZT. Multiple logistic regression analysis indicated that blastocyst
      transfer significantly increased the MZT rate in cases undergoing fresh ET.
      Ovarian stimulation, intracytoplasmic sperm injection, AH, and maternal age did
      not significantly affect the MZT incidence. CONCLUSIONS: Blastocyst transfer was
      associated with an increased MZT incidence. We have to be aware of the potential
      risk of MZT caused by blastocyst transfer. However, further studies are required
      to assess the correlation among specific AH types, embryo culture conditions, and
      MZT incidence.

PMID- 24722790
TI  - Haemodynamic changes with the use of neuromuscular electrical stimulation
      compared to intermittent pneumatic compression.
AB  - INTRODUCTION: Enhancement of peripheral circulation has been shown to be of
      benefit in many vascular disorders, and the clinical effectiveness of
      intermittent pneumatic compression is well established in peripheral vascular
      disease. This study compares the haemodynamic efficacy of a novel neuromuscular
      electrical stimulation device with intermittent pneumatic compression in healthy
      subjects. METHODS: Ten healthy volunteers (mean age 27.1 +/- 3.8 years, body mass
      index 24.8 +/- 3.6 kg/m(2)) were randomised into two groups, in an interventional
      crossover trial. Devices used were the SCD ExpressTM Compression System,
      (Covidien, Ireland) and the gekoTM, (Firstkind Ltd, UK). Devices were applied
      bilaterally, and haemodynamic measurements taken from the left leg. Changes to
      haemodynamic parameters (superficial femory artery and femoral vein) and laser
      Doppler measurements from the hand and foot were compared. RESULTS: Intermittent
      pneumatic compression caused 51% (p = 0.002), 5% (ns) and 3% (ns) median
      increases in venous peak velocity, time-averaged maximum velocity and volume
      flow, respectively; neuromuscular electrical stimulator stimulation caused a
      103%, 101% and 101% median increases in the same parameters (all p = 0.002). The
      benefit was lost upon deactivation. Intermittent pneumatic compression did not
      improve arterial haemodynamics. Neuromuscular electrical stimulator caused 11%,
      84% and 75% increase in arterial parameters (p < 0.01). Laser Doppler readings
      taken from the leg were increased by neuromuscular electrical stimulator (p <
      0.001), dropping after deactivation. For intermittent pneumatic compression, the
      readings decreased during use but increased after cessation. Hand flux signal
      dropped during activation of both devices, rising after cessation. DISCUSSION:
      The neuromuscular electrical stimulator device used in this study enhances venous
      flow and peak velocity in the legs of healthy subjects and is equal or superior
      to intermittent pneumatic compression. This warrants further clinical and
      economic evaluation for deep venous thrombosis prophylaxis and exploration of the
      haemodynamic effect in venous pathology. It also enhances arterial time-averaged
      maximum velocity and flow rate, which may prove to be of clinical use in the
      management of peripheral arterial disease. The effect on the microcirculation as
      evidenced by laser Doppler fluximetry may reflect a clinically beneficial target
      in microvascular disease, such as in the diabetic foot.

PMID- 24722791
TI  - Mechanistic insight into the hydroxylation of alkanes by a nonheme iron(V)-oxo
      complex.
AB  - Hydroxylation of alkanes by a mononuclear nonheme iron(V)-oxo complex,
      [Fe(V)(O)(TAML)](-), is initiated by a rate-determining hydrogen atom (H-atom)
      abstraction, followed by an oxygen non-rebound process. Evidence for the H-atom
      abstraction-oxygen non-rebound mechanism is obtained experimentally and supported
      by DFT calculations.

PMID- 24722792
TI  - A systematic review and meta-analysis of submaximal exercise-based equations to
      predict maximal oxygen uptake in young people.
AB  - Many equations to predict maximal oxygen uptake (VO2max) from submaximal exercise
      tests have been proposed for young people, but the composition and accuracy of
      these equations vary greatly. The purpose of this systematic review was to
      analyze all submaximal exercise-based equations to predict VO2max measured via
      direct gas analysis for use with young people. Five databases were systematically
      searched in February 2013. Studies were included if they used a submaximal,
      exercise-based method to predict VO2max; the actual VO2max was gas analyzed;
      participants were younger than 18 years; and equations included at least one
      submaximal exercise-based variable. A meta-analysis and narrative synthesis were
      conducted. Sixteen studies were included. The mean equation validity statistic
      was strong, r = .786 (95% CI 0.747-0.819). Subgroup meta-analysis suggests
      exercise mode may contribute to the overall model, with running- and walking
      based predictive equations reporting the highest mean r values (running r = .880;
      walking r = .821) and cycling the weakest (r = .743). Selection of the most
      appropriate equation should be guided by factors such as purpose, logistic
      limitations, appropriateness of the validation sample, the level of study bias,
      and the degree of accuracy. Suggestions regarding the most accurate equation for
      each exercise mode are provided. 

PMID- 24722793
TI  - Switching magnetic interactions in the NiFe Prussian Blue Analogue: an ab initio
      inspection.
AB  - The magnetic interaction in the Ni(ii)-Fe(iii) Prussian Blue Analogue is
      investigated by means of Difference Dedicated Configuration Interaction (DDCI)
      calculations. Embedded cluster calculations are performed to extract the exchange
      coupling constant J with respect to an opening of the Ni-NC-Fe bridge while
      maintaining a rigid Fe(CN)6 unit. It is shown that such active distortion
      significantly modifies the magnetic interaction scheme in the material. Not only
      a ferromagnetic to antiferromagnetic transition is observed, but the J value is
      varied from +11.4 cm(-1) to -12.5 cm(-1) when the Ni-Fe cyanide bridge is opened
      by 20 degrees . The enhancement of the intersite hopping electron transfer
      integral by a factor of 1.5 can be correlated with the observed Na(+)-ion
      mobility in a unified "cation-coupled electron transfer" (CCET) process. These
      results stress the complexity and originality of this class of compounds
      evidenced by the versatility of their magnetic network. 

PMID- 24722794
TI  - The relationships between the chemosensitivity of human gastric cancer to
      paclitaxel and the expressions of class III beta-tubulin, MAPT, and survivin.
AB  - Lack of effective biomarkers is one of the challenges in current chemotherapy to
      predict drug response and sensitivity. This study was carried out to investigate
      the relationships between the expressions of class III beta-tubulin, microtubule
      associated protein tau (MAPT), survivin, and the sensitivity of primary gastric
      cancer (GC) to paclitaxel treatment. Reverse transcription PCR and Western blot
      were used to evaluate the mRNA and protein expressions of class III beta-tubulin,
      MAPT, and survivin in fifty-four GC tissues. Viable tumor cells from gastric
      carcinomas were tested for their sensitivity to paclitaxel using adenosine
      triphosphate-based tumor chemosensitivity assay in vitro. Out of 54 samples, 30
      samples were sensitive to paclitaxel, while the other 24 samples were resistant.
      The overall efficacy of paclitaxel was 55.56% (30/54). The mRNA expressions of
      class III beta-tubulin and survivin were significantly correlated with the
      histological grade (P = 0.029, 0.009, respectively). The sensitivity of GC
      patients to paclitaxel treatment was inversely correlated with the mRNA and
      protein expressions of class III beta-tubulin (P < 0.01), MAPT (P < 0.05), and
      survivin (P < 0.05). A significant positive correlation was found between class
      III beta-tubulin and MAPT expression at mRNA and protein levels (mRNA: P = 0.037;
      protein: P = 0.001). Our results indicate that the expression levels of class III
      beta-tubulin, MAPT, and survivin are good biomarkers for predicting the
      sensitivity of GC to paclitaxel treatment.

PMID- 24722795
TI  - Exhaled breath temperature in NSCLC: could be a new non-invasive marker?
AB  - The exhaled breath temperature (EBT) has been proven to be the expression of
      airways inflammation as well as of the increased vascularity. Although both these
      conditions characterize lung cancer pathogenesis, this is the first study where
      the EBT has been analysed in patients affected by non-small-cell lung cancer. The
      aim of this study was to verify whether and how the lung cancer being examined
      influences the EBT for possible future clinical implications. Eighty-two
      consecutive subjects with a radiological suspicion of lung cancer were enrolled
      and underwent standard diagnostic and staging procedures for cancer. EBT was
      measured in all the subjects at the enrolment with the X-Halo device. Forty
      patients resulted as affected by lung cancer while 42 as false-positive
      (controls). We found a higher EBT in NSCLC patients compared to healthy subjects.
      The EBT was correlated with number of packs/year and associated with the stage of
      lung cancer. We identified a cut-off value for the EBT that is able to screen
      patients with lung cancer with a high sensitivity and specificity. Our results
      suggest that lung cancer causes an increase in the EBT, which, whether confirmed
      and validated, could become a new non-invasive clinical tool in the screening and
      monitoring of this disease. 

PMID- 24722796
TI  - The impact of functional LIG4 polymorphism on platinum-based chemotherapy
      response and survival in non-small cell lung cancer.
AB  - DNA repair capacity is correlated with the sensitivity of cancer cells toward
      platinum-based chemotherapy. The aim of this study was to investigate whether
      single-nucleotide polymorphisms (SNPs) in DNA repair genes NBS1, LIG4, and RAD51
      were correlated with tumor response in advanced non-small cell lung cancer
      (NSCLC) patients in a Chinese population who received platinum-based
      chemotherapy. The treatment outcomes of 146 advanced NSCLC patients who were
      treated with platinum-based chemotherapy were evaluated. The polymorphic status
      of three SNPs was determined by genotyping via the polymerase chain reaction
      restriction fragment length polymorphism method. Forty-five patients in the group
      with the CC genotype (45/90) showed a good response to treatment, while only 18
      patients in the CT+TT group (18/55) showed a good response, indicating a
      substantial differences in the chemotherapy response rate based on the LIG4
      Thr9Ile polymorphism (P = 0.042). Patients with the GG genotype for the NSB1
      Glu185Gln polymorphism were more sensitive to platinum-based chemotherapy
      compared with patients with either the CG or CC genotype (P = 0.001). Kaplan
      Meier analysis of all patients showed a significant association between the LIG4
      Thr9Ile CC polymorphism and superior progression-free survival and overall
      survival (log-rank P = 0.045 and 0.031, respectively). However, there were no
      significant differences in survival based on the LIG4 Thr9Ile or the RAD51 135G>C
      polymorphisms. Polymorphisms in the NSB1 and LIG4 genes may be a predictive
      marker for treatment response and for advanced NSCLC patients in stage IIIB + IV.
      The CC genotype of the LIG4 Thr9Ile polymorphism may also serve as an independent
      prognosis factor.

PMID- 24722797
TI  - High burden of extended-spectrum beta-lactamase-positive Escherichia coli in
      geriatric patients.
AB  - Few studies have described how an expanding elderly population influences the
      burden of antimicrobial resistance in micro-organisms. This study aimed to
      investigate trends in age-stratified extended-spectrum beta-lactamase (ESBL)
      positive Escherichia coli metrics in relation to an ageing population. The
      antimicrobial resistance database of E. coli from a healthcare region in Hong
      Kong from 2003 to 2012 was retrospectively reviewed. Future trends in age
      stratified ESBL metrics were predicted up to 2022. Susceptibility results of
      clinical E. coli isolates from patients aged 0-74 years (n = 17 853) and aged
      >=75 years (n = 17 047) were analysed. For the period 2003-2012, 23.7 % of the
      hospital admissions were of patients aged >=75 years. However, approximately half
      of the annual ESBL-positive E. coli isolates were recovered from patients aged
      >=75 years, being 55.0 % (233/424) in 2003 and 56.0 % (639/1142) in 2012. During
      this period of time, the annual prevalence and cumulative incidence of ESBL
      positive E. coli in patients aged >=75 years were significantly higher than in
      patients aged 0-74 years. From 2012-2022, it is predicted that ESBL-positive E.
      coli prevalence among patients aged 0-74 years and >=75 years would increase from
      25.4 % to 50.2 % and from 30.8 % to 70.0 %, respectively. In 2022, the predicted
      ESBL-positive E. coli cumulative incidence would be 63.7 per 10 000 admissions
      and 178.7 per 10 000 admissions among patients aged 0-74 years and >=75 years,
      respectively. In conclusion, a rapidly expanding elderly population would
      substantially add to the burden of ESBL.

PMID- 24722798
TI  - A novel Omp25-binding peptide screened by phage display can inhibit Brucella
      abortus 2308 infection in vitro and in vivo.
AB  - Brucellosis is a globally distributed zoonotic disease affecting animals and
      humans, and current antibiotic and vaccine strategies are not optimal. The
      surface-exposed protein Omp25 is involved in Brucella virulence and plays an
      important role in Brucella pathogenesis during infection, suggesting that Omp25
      could be a useful target for selecting potential therapeutic molecules to inhibit
      Brucella pathogenesis. In this study, we identified, we believe for the first
      time, peptides that bind specifically to the Omp25 protein of pathogens, using a
      phage panning technique, After four rounds of panning, 42 plaques of eluted
      phages were subjected to pyrosequencing. Four phage clones that bound better than
      the other clones were selected following confirmation by ELISA and affinity
      constant determination. The peptides selected could significantly inhibit
      Brucella abortus 2308 (S2308) internalization and intracellular growth in
      RAW264.7 macrophages, and significantly induce secretion of TNF-alpha and IL-12
      in peptide- and S2308-treated cells. Any observed peptide (OP11, OP27, OP35 or
      OP40) could significantly inhibit S2308 infection in BALB/c mice. Moreover, the
      peptide OP11 was the best candidate peptide for inhibiting S2308 infection in
      vitro and in vivo. These results suggest that peptide OP11 has potential for
      exploitation as a peptide drug in resisting S2308 infection.

PMID- 24722799
TI  - The calcineurin inhibitor cyclosporin A exhibits synergism with antifungals
      against Candida parapsilosis species complex.
AB  - Candida parapsilosis complex comprises three closely related species, C.
      parapsilosis sensu stricto, Candida metapsilosis and Candida orthopsilosis. In
      the last decade, antifungal resistance to azoles and caspofungin among C.
      parapsilosis sensu lato strains has been considered a matter of concern
      worldwide. In the present study, we evaluated the synergistic potential of
      antifungals and the calcineurin inhibitor cyclosporin A (Cys) against planktonic
      and biofilms of C. parapsilosis complex from clinical sources. Susceptibility
      assays with amphotericin, fluconazole, voriconazole, caspofungin and Cys were
      performed by microdilution in accordance with Clinical and Laboratory Standards
      Institute guidelines. Synergy testing against planktonic cells of C. parapsilosis
      sensu lato strains was assessed by the chequerboard method. Combinations formed
      by antifungals with Cys were evaluated against mature biofilms in microtitre
      plates. No differences in the antifungal susceptibility pattern among species
      were observed, but C. parapsilosis sensu stricto strains were more susceptible to
      Cys than C. orthopsilosis and C. metapsilosis. Synergism between antifungals and
      Cys was observed in C. parapsilosis sensu lato strains. Combinations formed by
      antifungals and Cys were able to prevent biofilm formation and showed an
      inhibitory effect against mature biofilms of C. parapsilosis sensu stricto, C.
      metapsilosis and C. orthopsilosis. These results strengthen the potential of
      calcineurin inhibition as a promising approach to enhance the efficiency of
      antifungal drugs. 

PMID- 24722801
TI  - Characters available in photoplethysmogram for blood pressure estimation: beyond
      the pulse transit time.
AB  - The continuous and noninvasive blood pressure (BP) measurement based on pulse
      transit time (PTT) doesn't need cuff and could monitor BP in real time for a long
      period. However, PTT is just a time index derived from electrocardiogram (ECG)
      and photoplethysmogram (PPG), while BP-related information within the PPG
      waveform has seldom been taken into consideration. We hypothesized that PPG
      waveform feature might be useful for BP estimation. Nine healthy subjects took
      part in an exercise stress test, including baseline resting, exercise on bicycle
      ergometry and recovering resting. ECG of lead V5 and PPG from left finger were
      collected simultaneously, and systolic blood pressure (SBP) and diastolic blood
      pressure (DBP) were recorded from a cuff sphygmometer on the right wrist. The
      correlation coefficients were obtained between BP (SBP, DBP and pulse pressure
      (PP)) and PPG morphological indices (total 15 indices in terms of waveform
      amplitude, time span and area ratio). Five PPG indices were correlated with both
      SBP and PP (absolute value of correlation coefficient |r| > 0.6) and were further
      tested for the capability to BP estimation, which were: (1) PTTA, time delay
      between the R peak of ECG and the foot point of PPG; (2) RSD, time ratio of
      systole to diastole; (3) RtArea, area ratio of systole to diastole; (4) TmBB,
      time span of PPG cycle; (5) TmCA, diastolic duration. Comparisons were made
      between the measured BP and the estimated BP by regression lines and quadratic
      curve fitting, respectively. As a result, the mean errors of SBP liner fitting
      with RSD, RtArea, TmBB and TmCA respectively were 5.5, 5.4, 5.2, 5.1 mmHg, which
      were smaller than that with PTTA of 5.8 mmHg. And the mean errors of SBP
      quadratic curve fitting with RSD, RtArea, TmBB and TmCA were all 5.1 mmHg, which
      were smaller than that with PTTA of 5.7 mmHg. The mean errors of multiple
      regression for SBP, PP and DBP was 4.7, 4.7, 3.5 mmHg respectively, which were
      more accurate than the regression with single PTTA of 5.8, 5.3, 5.2 mmHg
      respectively. However, PPG-based SBP and DBP could under estimate cuff pressure
      by 8 mmHg and over estimate by 10 mmHg respectively, which is a clinically
      significant error. In conclusion, the combination of time span (PTT, time ratio
      of systole to diastole, time span of PPG cycle and diastolic duration) and
      waveform morphology (area ratio of systole to diastole) could improve the
      performance of PPG-based BP estimation.

PMID- 24722800
TI  - Post-therapeutic response evaluation by a combination of endoscopy and CT scan in
      esophagogastric adenocarcinoma after chemotherapy: better than its reputation.
AB  - BACKGROUND: Neoadjuvant chemotherapy is an accepted standard of care for locally
      advanced esophagogastric cancer. As only a subgroup benefits, a response-based
      tailored treatment would be of interest. The aim of our study was the evaluation
      of the prognostic and predictive value of clinical response in esophagogastric
      adenocarcinomas. METHODS: Clinical response based on a combination of endoscopy
      and computed tomography (CT) scan was evaluated retrospectively within a
      prospective database in center A and then transferred to center B. A total of
      686/740 (A) and 184/210 (B) patients, staged cT3/4, cN0/1 underwent neoadjuvant
      chemotherapy and were then re-staged by endoscopy and CT before undergoing tumor
      resection. Of 184 patients, 118 (B) additionally had an interim response
      assessment 4-6 weeks after the start of chemotherapy. RESULTS: In A, 479 patients
      (70%) were defined as clinical nonresponders, 207 (30%) as responders. Median
      survival was 38 months (nonresponders: 27 months, responders: 108 months, log
      rank, p < 0.001). Clinical and histopathological response correlated
      significantly (p < 0.001). In multivariate analysis, clinical response was an
      independent prognostic factor (HR for death 1.4, 95% CI 1.0-1.8, p = 0.032). In
      B, 140 patients (76%) were nonresponders and 44 (24%) responded. Median survival
      was 33 months, (nonresponders: 27 months, responders: not reached, p = 0.003).
      Interim clinical response evaluation (118 patients) also had prognostic impact (p
      = 0.008). Interim, preoperative clinical response and histopathological response
      correlated strongly (p < 0.001). CONCLUSION: Preoperative clinical response was
      an independent prognostic factor in center A, while in center B its prognostic
      value could only be confirmed in univariate analysis. The accordance with
      histopathological response was good in both centers, and interim clinical
      response evaluation showed comparable results to preoperative evaluation.

PMID- 24722802
TI  - Transapical myectomy for severe mid-ventricular obstructive hypertrophic
      cardiomyopathy.

PMID- 24722803
TI  - Balancing stroke and bleeding risks in patients with atrial fibrillation and
      renal failure: the Swedish Atrial Fibrillation Cohort study.
AB  - BACKGROUND: Patients who have both atrial fibrillation (AF) and renal failure
      have an increased risk of thrombo-embolism. Renal failure is also a risk factor
      for bleeding, which makes decisions regarding thromboprophylaxis complicated. Our
      aim was to determine risks for ischaemic stroke and bleeding in patients with AF
      and renal failure in relation to anticoagulant strategies. METHODS AND RESULTS:
      This is retrospective non-randomized study of Swedish health registers comprising
      307 351 patients with AF, of whom 13 435 had a previous diagnosis of renal
      failure. Ischaemic stroke occurred more often in AF patients with renal failure
      (annual rate, 3.9% vs. no renal failure, 2.9%), but this was related to
      concomitant comorbidities [adjusted hazard ratio (HR) 1.02, 95% confidence
      interval (CI) 0.95-1.10]. Adding renal failure to the established stroke risk
      stratification schemes (CHADS2 and CHA2DS2-VASc) did not improve their predictive
      value. Renal failure was an independent risk factor for intracranial bleeding
      [adjusted HR: 1.27 (1.09-1.49)]. Most patients with renal failure benefited from
      warfarin treatment, despite their high bleeding risk. The incidence of the
      combined endpoint ischaemic or haemorrhagic stroke or death was lower among those
      who used warfarin than among those who did not use warfarin (adjusted HR: 0.76,
      CI 0.72-0.80). CONCLUSIONS: Patients with both AF and renal failure will probably
      benefit most from having the same treatment as is recommended for other patients
      with AF, without setting a higher or lower threshold for treatment. Adding
      additional points for renal failure to the CHADS2 and CHA2DS2-VASc scores did not
      improve their predictive value.

PMID- 24722804
TI  - ECG pitfall: anterior myocardial infarction in dextrocardia.

PMID- 24722805
TI  - Renin-angiotensin system blockade: time for a reappraisal?

PMID- 24722806
TI  - Contrast-induced nephropathy: the sin of primary percutaneous coronary
      intervention?

PMID- 24722807
TI  - Optical coherence tomography imaging of everolimus-eluting bioresorbable vascular
      scaffold implanted into coronary vein graft at 3-month follow-up.

PMID- 24722808
TI  - Combined intracardiac and epicardial device closure of a large left ventricular
      pseudoaneurysm.

PMID- 24722811
TI  - Engineering self-assembled N-doped graphene-carbon nanotube composites towards
      efficient oxygen reduction electrocatalysts.
AB  - The importance of the oxygen reduction reaction (ORR) in fuel cells and high
      energy density metal-air batteries has attracted intense research interests in
      looking for low-cost ORR catalysts as substitutes for expensive and scarce Pt
      based catalysts. N-doped graphene and carbon nanotubes prepared in a low-cost and
      scalable way have demonstrated their potential although the performance still
      needs to be improved. In view of the requirements for a high-performance ORR
      electrocatalyst, this work focused on developing the nanocomposites of N-doped
      reduced graphene oxide (N-rGO) and N-doped carbon nanotubes (N-CNT) as low-cost
      efficient ORR catalysts by integrating the advantages of abundant highly-active
      sites from N-rGO and a three-dimensional conductive network for efficient mass
      and electron transport from N-CNT. By optimizing the preparation method and
      dedicatedly tuning the composition, the much enhanced ORR activity and superior
      durability and tolerance to methanol were achieved for the self-assembled N-doped
      composite (N-rGO-CNT) at a mass ratio of 1 : 5 rGO/CNT. Further improvement of
      the ORR electrocatalytic activity of the composite was also demonstrated by
      introducing iron into the composite.

PMID- 24722810
TI  - Conjugation of amino-bioactive glasses with 5-aminofluorescein as probe molecule
      for the development of pH sensitive stimuli-responsive biomaterials.
AB  - Bioceramics, such as silica-based glasses, are widely used in bone and teeth
      restoration. Nowadays, the association between nanotechnology and pharmacology is
      one of the most promising research fields in cancer therapy. The advanced
      processing methods and new chemical strategies allow the incorporation of drugs
      within them or on their functionalized surfaces. Bioceramics can act as local
      drug delivery systems to treat bone and teeth diseases. The present paper reports
      data related to the development of a pH-stimuli responsive bioactive glass. The
      glass conjugation with 5-aminofluorescein (5-AF), through a pH-sensitive organic
      spacer, allows to produce a pH-responsive bioactive biomaterial: when it is
      exposed to specific pH changes, it can favour the release of 5-AF directly at the
      target site. 5-AF has been chosen as a simple, low cost, non toxic model to
      simulate doxorubicin, an anticancer drug. As doxorubicin, 5-AF contains an amino
      group in its structure in order to form an amide bond with the carboxylic
      functionalities of the glass. Raman spectroscopy and thermal analysis confirm the
      glass conjugation of 5-AF by means of an amide bond; the amount of 5-AF loaded
      was very high (~ 65 and 44 wt%). The release tests at two different pH (4.2 and
      7.4) show that the amount of released 5-AF is higher at acid pH with respect to
      physiological one. This preliminary datum evidenced that a pH-sensitive drug
      delivery system has been developed. The low amount of 5-AF released (<1 wt% of
      the total 5-AF) is due to the very low solubility of 5-AF in aqueous medium. This
      disadvantage, may be overcome in a dynamic environment (physiological
      conditions), where it is possible to obtain a drug release system ensuring an
      effective therapeutic dose for long times and, at the same time, avoiding the
      drug toxicity.

PMID- 24722812
TI  - Micropatterned biofilm formations by laminar flow-templating.
AB  - We present a microfluidic device capable of patterning linear biofilm formations
      using a flow templating approach. We describe the design considerations and
      fabrication methodology of a two level flow-templating micro-bioreactor (FT
      MUBR), which generates a biofilm growth stream surrounded on 3 sides by a growth
      inhibiting confinement stream. Through a combination of experiments and
      simulations we comprehensively evaluate and exploit control parameters to
      manipulate the biofilm growth template stream dimensions. The FT-MUBR is then
      used to grow biofilm patterns with controllable dimensions. A proof-of-principle
      study using the device demonstrates its utility in conducting biofilm growth rate
      measurements under different shear stress environments. This opens the way for
      quantitative studies into the effects of the local shear environment on biofilm
      properties and for the synthesis of a new generation of functional biomaterials
      with controllable properties. 

PMID- 24722813
TI  - Lower lateral cartilage repositioning: objective analysis using 3-dimensional
      imaging.
AB  - IMPORTANCE: In recent years, with the advent of 3-dimensional (3D) imaging
      techniques, it has become possible to objectively measure rhinoplasty results.
      However, few studies have used 3D imaging software to assess postoperative
      rhinoplasty results of the nasal tip. OBJECTIVE: To analyze nasal tip volumes of
      patients with bulbous tips and measure postoperative nasal tip volume changes in
      patients who have undergone lower lateral cartilage (LLC) repositioning. DESIGN,
      SETTING, AND PARTICIPANTS: A prospective study of patients with a preoperative
      diagnosis of bulbous nasal tip and cephalically oriented LLC as measured
      intraoperatively (with angles less than 30 degrees from the midline) who
      underwent rhinoplasty by a single surgeon and preoperative and postoperative 3dMD
      imaging at a university hospital. INTERVENTIONS: Rhinoplasty with LLC
      repositioning and preoperative and postoperative 3dMD system imaging. We also
      used 3dMD Vultus software for the analysis of nasal tip volume changes. MAIN
      OUTCOMES AND MEASURES: Changes in nasal tip volume and LLC angle. RESULTS: Thirty
      one patients met the inclusion criteria (25 women and 6 men; mean age, 33 years).
      Among these, there were 16 primary and 15 revision cases with a follow-up range
      of 1 to 19 months. Statistical tests included a paired t test on volume and angle
      changes as well as correlative and exploratory analyses to gain further insight
      into the analysis population over time. The change in the LLC angle after
      repositioning was found to be statistically significant. The mean decrease in
      volume on the right was 0.0254 mL, and the mean decrease on the left was 0.0249
      mL. The mean total volume change was a decrease of 0.0503 mL. An exploratory
      analysis suggested that subjects with longer follow-up displayed a greater
      reduction in volume. Using 5 months as a cutoff, we found that the subgroup with
      longer follow-up displayed a mean total bilateral volume change of -0.07 mL
      compared with -0.03 mL in the subgroup with shorter follow-up. CONCLUSIONS AND
      RELEVANCE: We found that LLC repositioning when used to address bulbous nasal
      tips and cephalically oriented LLCs leads to significant increase (preoperative
      to postoperative) in the angle of the LLC (to a more caudal orientation). We also
      found an overall trend of decreasing nasal tip volume throughout follow-up.
      Although not statistically significant, the overall decrease in volume is
      clinically meaningful when paired with favorable positioning of the LLC.
      Exploratory analyses suggest that treatment effect is consistent across sexes and
      that greater decrease in total volume might be found with longer follow-up. LEVEL
      OF EVIDENCE: 4.

PMID- 24722814
TI  - Approaches to Mixed Methods Dissemination and Implementation Research: Methods,
      Strengths, Caveats, and Opportunities.
AB  - Limited translation of research into practice has prompted study of diffusion and
      implementation, and development of effective methods of encouraging adoption,
      dissemination and implementation. Mixed methods techniques offer approaches for
      assessing and addressing processes affecting implementation of evidence-based
      interventions. We describe common mixed methods approaches used in dissemination
      and implementation research, discuss strengths and limitations of mixed methods
      approaches to data collection, and suggest promising methods not yet widely used
      in implementation research. We review qualitative, quantitative, and hybrid
      approaches to mixed methods dissemination and implementation studies, and
      describe methods for integrating multiple methods to increase depth of
      understanding while improving reliability and validity of findings. 

PMID- 24722815
TI  - Reducing firearm-related injuries and deaths in the United States: executive
      summary of a policy position paper from the American College of Physicians.

PMID- 24722816
TI  - F 16915 prevents heart failure-induced atrial fibrillation: a promising new drug
      as upstream therapy.
AB  - Atrial fibrillation (AF) is a common complication of heart failure. The aim of
      the present study was to investigate the effects of a new pure docosahexaenoic
      acid derivative called F 16915 in experimental models of heart failure-induced
      atria dysfunction. The atrial dysfunction-induced AF was investigated (1) in a
      dog model of tachypacing-induced congestive heart failure and (2) in a rat model
      of heart failure induced by occlusion of left descending coronary artery and 2
      months reperfusion. F 16915 (5 g/day for 4 weeks) significantly reduced the mean
      duration of AF induced by burst pacing in the dog model (989 +/- 111 s in the
      vehicle group to 79 +/- 59 s with F 16915, P < 0.01). This dose of F 16915 also
      significantly reduced the incidence of sustained AF (5/5 dogs in the vehicle
      group versus 1/5 with F 16915, P < 0.05). In the rat model, the percentage of
      shortening fraction in the F 16915 group (100 mg/kg p.o. daily) was significantly
      restored after 2 months (32.6 +/- 7.4 %, n = 9 vs 17.6 +/- 3.4 %, n = 9 in the
      vehicle group, P < 0.01). F 16915 also reduced the de-phosphorylation of
      connexin43 from atria tissue. The present results show that treatment with F
      16915 reduced the heart dilation, resynchronized the gap junction activity, and
      reduced the AF duration in models of heart failure. Thus, F 16915 constitutes a
      promising new drug as upstream therapy for the treatment of AF in patients with
      heart failure.

PMID- 24722817
TI  - Hypothermia attenuates NO production in anesthetized rats with endotoxemia.
AB  - Sepsis is often associated with upregulation of nitric oxide production and
      fever, and it is common to control an excessive febrile response with antipyretic
      therapy and external cooling. Our aim was to evaluate the effect of hypothermia
      on NO production in a model of septic shock. Rats were anesthetized, ventilated,
      and instrumented for hemodynamic monitoring and divided into four groups.
      Normothermic controls (NC) received saline intravenously and were maintained at
      37  degrees C. Hypothermic controls (HC) received saline but were allowed to
      become hypothermic. Normothermic endotoxic (NE) received Escherichia Coli
      lipopolysaccharides (LPS) intravenously to induce endotoxic shock and was
      maintained at 37  degrees C. Hypothermic endotoxic (HE) received LPS
      intravenously and was allowed to become hypothermic. Exhaled NO (NOe) was
      measured from mixed expired gas at time zero and every 30 min, for 5 h. After
      injection of LPS, NOe increased substantially in the NE group (700 +/- 24 ppb),
      but increased only to 25 +/- 2 ppb in the HE group. NOe increased to 90 +/- 3 ppb
      in the NC group, and to 17.6 +/- 3.1 ppb in the HC group after 5 h (P < 0.05),
      whilst blood pressure remained stable. In the HE group, blood pressure fell
      immediately after injection of the LPS, but thereafter remained stable despite
      the rise in NOe. In the NE group, the blood pressure fell gradually, and the
      animals became hypotensive. During the natural course of endotoxemia in
      anesthetized rats, allowing severe hypothermia to ensue by not actively managing
      temperature and hemodynamics resulted in significantly reduced expired NO
      concentrations, lung injury, and prolonged survival. The clinical benefits of
      such a finding currently remain unclear and merit further investigation.

PMID- 24722818
TI  - Gallic acid functions as a TRPA1 antagonist with relevant antinociceptive and
      antiedematogenic effects in mice.
AB  - The transient receptor potential ankyrin 1 (TRPA1) has been identified as a
      relevant target for the development of novel analgesics. Gallic acid (GA) is a
      polyphenolic compound commonly found in green tea and various berries and
      possesses a wide range of biological activities. The goal of this study was to
      identify GA as a TRPA1 antagonist and observe its antinociceptive effects in
      different pain models. First, we evaluated the ability of GA to affect
      cinnamaldehyde-induced calcium influx. Then, we observed the antinociceptive and
      antiedematogenic effects of GA (3-100 mg/kg) oral administration after the
      intraplantar (i.pl.) injection of TRPA1 agonists (allyl isothiocyanate,
      cinnamaldehyde, or hydrogen peroxide-H2O2) in either an inflammatory pain model
      (carrageenan i.pl. injection) or a neuropathic pain model (chronic constriction
      injury) in male Swiss mice (25-35 g). GA reduced the calcium influx mediated by
      TRPA1 activation. Moreover, the oral administration of GA decreased the
      spontaneous nociception triggered by allyl isothiocyanate, cinnamaldehyde, and
      H2O2. Carrageenan-induced allodynia and edema were largely reduced by the
      pretreatment with GA. Moreover, the administration of GA was also capable of
      decreasing cold and mechanical allodynia in a neuropathic pain model. Finally, GA
      was absorbed after oral administration and did not produce any detectable side
      effects. In conclusion, we found that GA is a TRPA1 antagonist with
      antinociceptive properties in relevant models of clinical pain without detectable
      side effects, which makes it a good candidate for the treatment of painful
      conditions.

PMID- 24722819
TI  - Psychophysiological responses to overloading and tapering phases in elite young
      soccer players.
AB  - This study investigated the effect of a 2-week overloading training phase
      followed by a 2-week tapering phase on internal training load (ITL), salivary
      cortisol, stress tolerance, and upper respiratory tract infections symptoms
      (URTI) in 11 male young soccer players (16.0 +/- 0.5 yrs). Ratings of perceived
      exertion (session- RPE) were taken after each training session (N = 194) to
      determine ITL. Saliva sampling was conducted at the end of each week and cortisol
      concentration assessed by ELISA. DALDA and WURSS-21 questionnaires were
      administered every week to evaluate stress tolerance and severity of URTI
      respectively. The number of athletes reporting URTI symptoms was recorded. The
      overloading phase promoted greater ITL and a higher resting cortisol
      concentration than the tapering phase (P < .05). While no significant changes in
      stress tolerance or URTI severity were observed, the number of athletes reporting
      URTI symptoms was higher during the overloading phase. A significant correlation
      was observed between symptoms of stress and severity of URTI (rs=-.71; P = .01).
      The results indicate that an integrated approach using psychological measures
      (session-RPE and DALDA), self-reports of URTI symptoms, and endocrine responses
      (cortisol) to training are pertinent for monitoring young soccer players. 

PMID- 24722821
TI  - Underwater superoleophobic graphene oxide coated meshes for the separation of oil
      and water.
AB  - Hydrophilic graphene oxide (GO) nanosheets can be easily coated onto stainless
      steel meshes. Compared to neat meshes, GO coated meshes become more hydrophilic
      in air and superoleophobic under water. Taking advantage of this completely
      opposite wettability, GO coated meshes were used for gravity-driven oil-water
      separation. 

PMID- 24722820
TI  - Vitamin D therapy in experimental allergic encephalomyelitis could be limited by
      opposing effects of sphingosine 1-phosphate and gelsolin dysregulation.
AB  - Several studies support a protective effect of vitamin D on multiple sclerosis
      and experimental allergic encephalomyelitis (EAE), but the mechanisms of these
      favorable effects are unclear. Our study demonstrates that sphingosine 1
      phosphate (S1P) is upregulated in the serum and spinal cords of EAE rats, but
      that vitamin D reverses the upregulation to alleviate inflammation. Vitamin D,
      however, cannot prevent the disease process, suggesting that other factors may be
      involved. To identify additional factors that might limit vitamin D efficacy, we
      assessed the effects of vitamin D on plasma gelsolin (pGSN), a regulator of S1P
      that is downregulated in the CSF of MS patients. Our results show that pGSN is
      downregulated in the serum of EAE rats, whereas its cellular form, cytoplasmic
      gelsolin (cGSN), is upregulated in the spinal cord of EAE rats. Importantly,
      vitamin D causes a downregulation of both pGSN and cGSN, which may counteract the
      positive effects of S1P decrease. Furthermore, 48 and 42 kDa caspase-3 cleavage
      products of cGSN are detected in EAE spinal cords, suggesting enhanced apoptotic
      activity, but these cleaved products undergo a similar decrease upon vitamin D
      treatment. To directly test the role of cGSN in the apoptotic process, we
      performed RNA interference in PC-12, a rat sympathetic nerve cell line. Results
      verify that cGSN suppresses apoptosis induced by TNF-alpha. Collectively, these
      results support a therapeutic effect of vitamin D that is derived from its
      ability to reduce S1P, but is limited by its simultaneous effect in reducing pGSN
      and cGSN. Based on these observations, we postulate that combined therapy with
      recombinant human pGSN and vitamin D may produce more beneficial effect in
      treating multiple sclerosis.

PMID- 24722822
TI  - Thyroid imaging reporting and data system (TI-RADS) in the diagnostic value of
      thyroid nodules: a systematic review.
AB  - This review was to assess the overall diagnostic accuracy of thyroid imaging
      reporting and data system (TI-RADS) classification in the differentiated
      diagnosis of patients with thyroid nodules. The diagnostic accuracy of TI-RADS
      was identified by using data from PubMed, the Cochrane Library, and other
      databases, which was from Jan 1966 to Dec 2013. Meta-analysis methods were used
      to obtain pooled sensitivity, specificity, negative likelihood ratio, positive
      likelihood ratio, diagnostic odds ratio, and summary receiver operating
      characteristic curves. A total of five studies with 7,753 thyroid nodules
      enrolled met the inclusion criteria in this meta-analysis. TI-RADS had a pooled
      sensitivity of 0.75 (95 % confidence interval 0.72-0.78) and a pooled specificity
      of 0.69 (95 % confidence interval 0.68-0.70). The pooled diagnostic odds ratio
      was 24.28 (95 % confidence interval 14.25-41.38). The overall area under the
      curve was 0.9177, and the Q* index was 0.8304. The TI-RADS classification was the
      accurate diagnostic technique for differentiating thyroid nodules.

PMID- 24722823
TI  - Diagnostic value of CD117 in differential diagnosis of acute leukemias.
AB  - C-kit receptor (CD117) and its ligand, stem cell factor, play a key role in
      normal hematopoiesis. It has been demonstrated that its expression extremely
      increases in leukemias with myeloid commitment. We analyzed findings on CD117
      expression together with other myeloid related markers in 203 de novo acute
      leukemias, referred to Iranian immunophenotyping centers: Iranian Blood
      Transfusion Organization (IBTO) and Baghiatallah Hospital (BH). All cases were
      characterized based on the French American British cooperative group (FAB) and
      European Group for Immunological Classification of Leukemias (EGIL). The cases
      comprised of 111 acute myeloblastic leukemia (AML), 86 acute lymphoblastic
      leukemia (ALL), and 6 acute undifferentiated leukemia (AUL). CD117 was positive
      in 75 % of AML and 50 % of AUL, whereas none of the ALL cases was positive for
      this marker. Although CD117 was positive in 100 % of M5a cases, no M5b positive
      was found (p = 0.036). The calculated specificity for myeloid involvement was 100
      % for CD117 and CD33, and 98 % for CD13 and CD15 (p < 0.001). The calculated
      sensitivity for myeloid involvement was 83, 76, 64, and 41 % for CD13, CD117,
      CD33, and CD15, respectively (p < 0.001). We concluded that CD117 expression is a
      specific and rather sensitive marker for differential diagnosis between AML and
      ALL, and except for M5 subtypes, it fails to determine FAB subtypes; lack of
      expression in M5 can identify M5b. Therefore, it should be included in the
      routine primary panel for diagnosis of acute leukemias.

PMID- 24722824
TI  - Clinical significance of serum tenascin-c levels in epithelial ovarian cancer.
AB  - Tenascin-C (TNC) is an extracellular matrix protein that is expressed at low
      levels in normal adult tissue but is highly expressed around many tumors
      including ovarian tumors. The objective of this study was to determine the
      clinical significance of the serum levels of TNC in epithelial ovarian cancer
      (EOC) patients. A total of 50 patients with a pathologically confirmed diagnosis
      of EOC were included in this study. Serum TNC levels were determined by the solid
      phase sandwich enzyme-linked immunosorbent assay (ELISA) method. Age- and sex-
      matched 28 healthy controls were included in the analysis. Median age of the
      patients was 56.5 years old, range 22 to 83 years. Majority of the patients had
      advanced disease (FIGO stage III-IV) (90 %). The median serum TNC levels were
      found significantly higher in EOC patients (130.5 pg/mL) compared to healthy
      controls (90.1 pg/mL) (p = 0.03). We found no correlation between serum TNC
      levels and any prognostic parameters analyzed, including age of the patients,
      histology, tumor grade, stage of the disease, and response to chemotherapy.
      Survival analysis did not show statistically significant effect of serum TNC
      concentration on progression-free and overall survival (p = 0.36 and p = 0.19,
      respectively). However, patients with high serum TNC levels tend to have poor
      overall survival. In conclusion, although serum TNC levels are elevated, it has
      no predictive or prognostic roles on survival in EOC patients.

PMID- 24722825
TI  - Dissemination activities: a critical new role for substance abuse treatment
      organizations.
AB  - The Affordable Care Act calls for integration of substance abuse treatment into
      medical care via medical homes and continuing specialty care. For this
      integration to occur in the substance abuse treatment field, substantial sharing
      and dissemination of information by treatment providers is required. This study
      explored the determinants of organizational activities directed at disseminating
      evidence-based practices (EBPs) undertaken by 193 community treatment programs
      who are members of the National Institute on Drug Abuse (NIDA) Clinical Trials
      Network. Using factor analysis, the research identified two generic categories
      reflecting different motivations for dissemination activities and explored both
      treatment center leadership and organizational characteristics as determinants of
      these different types of dissemination activities. Organizational characteristics
      predicting treatment center dissemination activities included size, previous
      involvement in research protocols, linkages with other providers, and having non
      profit status. The treatment center leader's membership in professional
      organizations was also a significant determinant. Organization variables account
      for a larger portion of the variance in treatment center dissemination
      activities. The results suggest that the willingness of treatment providers to
      help disseminate EBPs within the industry may be heavily influenced through
      shared network connections with other treatment organizations. 

PMID- 24722827
TI  - Fluoropolymer surface coatings to control droplets in microfluidic devices.
AB  - We have demonstrated the application of low surface energy fluoropolymer coatings
      onto poly(dimethylsiloxane) (PDMS) microfluidic devices for droplet formation and
      extraction-induced merger of droplets. Initiated chemical vapor deposition (iCVD)
      was used to pattern fluoropolymer coatings within microchannels based on
      geometrical constraints. In a two-phase flow system, the range of accessible flow
      rates for droplet formation was greatly enhanced in the coated devices. The
      ability to controllably apply the coating only at the inlet facilitated a method
      for merging droplets. An organic spacer droplet was extracted from between a pair
      of aqueous droplets. The size of the organic droplet and the flow rate controlled
      the time to merge the aqueous droplets; the process of merging was independent of
      the droplet sizes. Extraction-induced droplet merging is a robust method for
      manipulating droplets that could be applied in translating multi-step reactions
      to microfluidic platforms. 

PMID- 24722826
TI  - Psychosocial predictors of weight regain in the weight loss maintenance trial.
AB  - This study's purpose was to identify psychosocial predictors of weight loss
      maintenance in a multi-site clinical trial, following a group-based weight loss
      program. Participants (N = 1025) were predominately women (63%) and 38% were
      Black (mean age = 55.6 years; SD = 8.7). At 12 months, higher SF-36 mental health
      composite scores were associated with less weight regain (p < .01). For Black
      participants, an interaction existed between race and friends' encouragement for
      exercise, where higher exercise encouragement was related to more weight regain
      (p < .05). At 30 months, friends' encouragement for healthy eating was associated
      with more weight regain (p < .05), whereas higher SF-36 mental health composite
      scores were related to less weight regain (p < .0001). Perceived stress and
      select health-related quality of life indices were associated with weight regain;
      this relationship varied across gender, race, and treatment conditions. Temporal
      changes in these variables should be investigated for their impact on weight
      maintenance.

PMID- 24722828
TI  - Alkali cation specific adsorption onto fcc(111) transition metal electrodes.
AB  - The presence of alkali cations in electrolyte solutions is known to impact the
      rate of electrocatalytic reactions, though the mechanism of such impact is not
      conclusively determined. We use density functional theory (DFT) to examine the
      specific adsorption of alkali cations to fcc(111) electrode surfaces, as specific
      adsorption may block catalyst sites or otherwise impact surface catalytic
      chemistry. Solvation of the cation-metal surface structure was investigated using
      explicit water models. Computed equilibrium potentials for alkali cation
      adsorption suggest that alkali and alkaline earth cations will specifically
      adsorb onto Pt(111) and Pd(111) surfaces in the potential range of hydrogen
      oxidation and hydrogen evolution catalysis in alkaline solutions. 

PMID- 24722829
TI  - Canonical transient receptor potential channel 2 (TRPC2): old name-new games.
      Importance in regulating of rat thyroid cell physiology.
AB  - In addition to the TSH-cyclic AMP signalling pathway, calcium signalling is of
      crucial importance in thyroid cells. Although the importance of calcium
      signalling has been thoroughly investigated for several decades, the nature of
      the calcium channels involved in signalling is unknown. In a recent series of
      investigations using the well-studied rat thyroid FRTL-5 cell line, we showed
      that these cells exclusively express the transient receptor potential canonical 2
      (TRPC2) channel. Our results suggested that the TRPC2 channel is of significant
      importance in regulating thyroid cell function. These investigations were the
      first to show that thyroid cells express a member of the TRPC family of ion
      channels. In this review, we will describe the importance of the TRPC2 channel in
      regulating TSH receptor expression, thyroglobulin maturation, intracellular
      calcium and iodide homeostasis and that the channel also regulates thyroid cell
      proliferation. 

PMID- 24722830
TI  - Characteristic of c-Kit+ progenitor cells in explanted human hearts.
AB  - According to literature data, self-renewing, multipotent, and clonogenic cardiac
      c-Kit(+) progenitor cells occur within human myocardium. The aim of this study
      was to isolate and characterize c-Kit(+) progenitor cells from explanted human
      hearts. Experimental material was obtained from 19 adult and 7 pediatric
      patients. Successful isolation and culture was achieved for 95 samples (84.1%)
      derived from five different regions of the heart: right and left ventricles,
      atrium, intraventricular septum, and apex. The average percentage of c-Kit(+)
      cells, as assessed by FACS, ranged between 0.7 and 0.9%. In contrast to published
      data we do not observed statistically significant differences in the number of c
      Kit(+) cells between disease-specific groups, parts of the heart or sexes.
      Nevertheless, c-Kit(+) cells were present in significant numbers (11-24%) in
      samples derived from three explanted pediatric hearts. c-Kit(+) cells were also
      positive for CD105 and a majority of them was positive for CD31 and CD34 (83.7 +/
      8.6 and 75.7 +/- 11.4%, respectively). Immunohistochemical analysis of the heart
      tissue revealed that most cells possessing the c-Kit antigen were also positive
      for tryptase, a specific mast cell marker. However, flow cytometry analysis has
      shown cultured c-Kit(+) cells to be negative for hematopoietic marker CD45 and
      mast cell marker CD33. Isolated c-Kit(+) cells display mesenchymal stem cell
      features and are thought to differentiate into endothelial cells.

PMID- 24722831
TI  - Airborne fine particulate matter induces multiple cell death pathways in human
      lung epithelial cells.
AB  - Our group was the first one reporting that autophagy could be triggered by
      airborne fine particulate matter (PM) with a mean diameter of less than 2.5 MUm
      (PM2.5) in human lung epithelial A549 cells, which could potentially lead to cell
      death. In the present study, we further explored the potential interactions
      between autophagy and apoptosis because it was well documented that PM2.5 could
      induce apoptosis in A549 cells. Much to our surprise, we found that PM2.5
      exposure caused oxidative stress, resulting in activation of multiple cell death
      pathways in A549 cells, that is, the tumor necrosis factor-alpha (TNF-alpha)
      induced pathway as evidenced by TNF-alpha secretion and activation of caspase-8
      and -3, the intrinsic apoptosis pathway as evidenced by increased expression of
      pro-apoptotic protein Bax, decreased expression of anti-apoptotic protein Bcl-2,
      disruption of mitochondrial membrane potential, and activation of caspase-9 and 
      3, and autophagy as evidenced by an increased number of double-membrane vesicles,
      accompanied by increases of conversion and punctuation of microtubule-associated
      proteins light chain 3 (LC3) and expression of Beclin 1. It appears that reactive
      oxygen species (ROS) function as signaling molecules for all the three pathways
      because pretreatment with N-acetylcysteine, a scavenger of ROS, almost completely
      abolished TNF-alpha secretion and significantly reduced the number of apoptotic
      and autophagic cells. In another aspect, inhibiting autophagy with 3
      methyladenine, a specific autophagy inhibitor, enhanced PM2.5-induced apoptosis
      and cytotoxicity. Intriguingly, neutralization of TNF-alpha with an anti-TNF
      alpha special antibody not only abolished activation of caspase-8, but also
      drastically reduced LC3-II conversion. Thus, the present study has provided novel
      insights into the mechanism of cytotoxicity and even pathogenesis of diseases
      associated with PM2.5 exposure. 

PMID- 24722832
TI  - Overexpression of CREB protein protects from tunicamycin-induced apoptosis in
      various rat cell types.
AB  - Endoplasmic reticulum (ER) stress plays an essential role in unfolded protein
      response induced apoptosis contributing to several pathological conditions.
      Glycogen synthase kinase-3beta (GSK-3beta) plays a central role in several
      apoptotic signaling, including ER stress, as the active form of GSK-3beta induces
      apoptosis. The phosphorylation of cAMP responsive element (CRE) binding protein
      (CREB) Ser-133 (S133) residue is the end-point of various signaling pathways,
      like growth factor signaling, while the Ser-129 (S129) residue is phosphorylated
      by GSK-3beta. The significance of the ubiquitously expressed transcription factor
      CREB is demonstrated in prolonged, tunicamycin (TM)-induced ER stress in this
      study. In the experiments wild-type (wt) CREB, S129Ala, S133Ala or S129Ala
      S133Ala mutant CREB expressing PC12 rat pheochromocytoma cell lines showed
      increased survival under TM-evoked prolonged ER stress compared to wtPC12 cells.
      After TM treatment ER stress was activated in all PC12 cell types. Lithium and SB
      216763, the selective, well-known inhibitors of GSK-3beta, decreased TM-induced
      apoptosis and promoted cell survival. The proapoptotic BH3-only Bcl-2 family
      member Bcl-2-interacting mediator of cell death (Bim) level was decreased in the
      different CREB overexpressing PC12 cells as a result of TM treatment. CREB
      overexpression also inhibited the sequestration of Bim protein from tubulin
      molecules, as it was demonstrated in wtPC12 cells. Transient expression of wtCREB
      diminished TM-induced apoptosis in wtPC12, Rat-1 and primary rat vascular smooth
      muscle cells. These findings demonstrate a novel role of CREB in different cell
      types as a potent protector against ER stress. 

PMID- 24722833
TI  - Evaluation of a Test Battery to Assess Perception of Music in Children With
      Cochlear Implants.
AB  - IMPORTANCE: A number of studies have investigated music perception in adult
      cochlear implant (CI) users. However, little is known about how pediatric CI
      users perceive and process music, in part because suitable methods for assessing
      music perception in this population are lacking. Therefore, we developed the
      Music in Children With Cochlear Implants (MCCI) battery to assess music
      perception in pediatric CI users younger than 9 years. OBJECTIVE: To pilot test
      the MCCI on a group of pediatric CI users to determine its feasibility for
      measuring music perception and to compare performance of CI users with that of
      normal-hearing (NH) control participants. DESIGN, SETTING, AND PARTICIPANTS: The
      pilot test was conducted in an academic tertiary care center. The MCCI evaluated
      rhythm, pitch, melody, harmony, and timbre perception. For each section, 10
      pediatric CI users and 10 NH controls were presented with a pair of stimuli that
      possibly varied along a single musical element (eg, rhythm). Participants were
      required to indicate whether the stimuli in the pair were the same or different.
      INTERVENTIONS: Administration of the MCCI. MAIN OUTCOMES AND MEASURES: Percentage
      correct on each section of the MCCI and the aggregate score of all sections by
      group. RESULTS: The MCCI provided a basic characterization of musical perceptual
      abilities. In the aggregate, NH controls significantly outperformed CI users in
      music perception (mean [SD] accuracy for CI users vs NH controls: rhythm, 73%
      [20%] vs 78% [20%]; pitch, 84% [12%] vs 91% [13%]; melody, 65% [16%] vs 75%
      [18%]; harmony, 74% [13%] vs 75% [14%]; and timbre, 80% [17%] vs 90% [12%];
      repeated-measures analysis of variance, F1,17 = 9.3; P < .01). Despite obtaining
      lower accuracies than NH controls, however, the CI users achieved above-chance
      accuracy in all sections of the MCCI (1-sample t test, P < .01), including pitch
      based sections that are traditionally difficult for CI users. These results
      suggest that CI users can make use of temporal and spectral cues to discriminate
      between musical stimuli, although not to the extent of their NH peers.
      CONCLUSIONS AND RELEVANCE: The MCCI provided an efficient and user-friendly
      assessment of music perception in pediatric CI users. This test battery may serve
      as a valuable tool to evaluate music perceptual abilities of pediatric CI users
      and measure the effects of interventions.

PMID- 24722834
TI  - Assessing modes and frequency of commuting to school in youngsters: a systematic
      review.
AB  - The first objective was to review and analyze self-reported measures used for
      assessing mode and frequency of commuting to and from school in youngsters (4
      18.5 years old). The secondary objective was to conduct a qualitative appraisal
      of the identified studies. We searched five online databases: PubMed,
      SportDiscus, ProQuest, National Transportation Library, and Web of Knowledge.
      Four categories of search terms were identified: self-report, active
      transportation, school-aged children and school. Titles and abstracts were
      reviewed to determine whether the studies met the inclusion criteria. The quality
      of the reporting of the measures was assessed using a tailored list. The
      electronic search strategy produced 5,898 studies. After applying the inclusion
      criteria, we identified 158 studies. Sixty-three studies (39.8%) specified the
      question about modes of commuting to school. One hundred seven studies (67.7%)
      directly questioned the study subjects (i.e., children and/or adolescents).
      Twenty studies (12.7%) posed a valid and reliable question. The quality
      assessment of the self-report measures was medium. The self-report measures used
      in the literature for assessing commuting to school tend to be heterogeneous and
      make difficult interstudies comparisons. Therefore we put forward the idea of a
      standard question designed to elicit reliable, comparable information on
      commuting to school. 

PMID- 24722835
TI  - Measurements of the in vitro anti-mycobacterial activity of ivermectin are method
      dependent--authors' response.

PMID- 24722836
TI  - Emergence and maintenance of multidrug-resistant Escherichia coli of canine
      origin harbouring a blaCMY-2-IncI1/ST65 plasmid and topoisomerase mutations.
AB  - OBJECTIVES: To characterize the mechanisms implicated in fluoroquinolone (FQ) and
      expanded-spectrum cephalosporin (ESC) resistance in three clinical and seven
      faecal multidrug-resistant (MDR; resistant to at least three antimicrobial
      classes) Escherichia coli isolates from a dog with atopic dermatitis, also
      suffering from recurrent otitis, that had already been exposed to prolonged
      antimicrobial treatment and colonized for a long period. METHODS: MICs of FQs,
      ESCs and other antimicrobials were determined by the broth microdilution method.
      Phenotypic tests (efflux pump inhibition and combination disc tests) and
      isoelectric focusing were combined with genotypic analyses [PCRs, sequencing,
      conjugation, S1 nuclease PFGE, PCR-based replicon typing, plasmid multilocus
      sequence typing (pMLST) and PCR mapping] to characterize the molecular basis of
      FQ and ESC resistance. Isolates were further characterized by MLST and PFGE.
      RESULTS: Three otitis and five faecal isolates with enrofloxacin MICs of 32 to
      >128 mg/L displayed the GyrA:S83L+D87N/ParC:E62K/ParE:G545D pattern harbouring
      novel ParC and ParE substitutions, whereas the two remaining faecal isolates were
      susceptible or borderline resistant single-step mutants (GyrA:S83L pattern) and
      carried qnrS1. Efflux pump overexpression also contributed to FQ resistance and
      the MDR phenotype. The three otitis and five faecal isolates also exhibited
      cefoxitin/ceftazidime MICs of 32-64 mg/L and harboured blaCMY-2, adjusted to
      ISEcp1, on an IncI1/ST65 conjugative plasmid, previously described in Salmonella
      Heidelberg from poultry. Interestingly, all isolates shared an identical MLST
      type (ST212), with the otitis isolates showing indistinguishable patterns with
      the high-level resistant faecal E. coli isolates. CONCLUSIONS: The long-term
      maintenance of FQ- and ESC-resistant clones harbouring topoisomerase mutations
      and a blaCMY-2-IncI1/ST65 plasmid in canine commensal flora after prolonged
      antimicrobial use may contribute to the dissemination of multidrug resistance.

PMID- 24722837
TI  - Suramin is a potent and selective inhibitor of Mycobacterium tuberculosis RecA
      protein and the SOS response: RecA as a potential target for antibacterial drug
      discovery.
AB  - OBJECTIVES: In eubacteria, RecA is essential for recombinational DNA repair and
      for stalled replication forks to resume DNA synthesis. Recent work has implicated
      a role for RecA in the development of antibiotic resistance in pathogenic
      bacteria. Consequently, our goal is to identify and characterize small-molecule
      inhibitors that target RecA both in vitro and in vivo. METHODS: We employed
      ATPase, DNA strand exchange and LexA cleavage assays to elucidate the inhibitory
      effects of suramin on Mycobacterium tuberculosis RecA. To gain insights into the
      mechanism of suramin action, we directly visualized the structure of RecA
      nucleoprotein filaments by atomic force microscopy. To determine the specificity
      of suramin action in vivo, we investigated its effect on the SOS response by pull
      down and western blot assays as well as for its antibacterial activity. RESULTS:
      We show that suramin is a potent inhibitor of DNA strand exchange and ATPase
      activities of bacterial RecA proteins with IC(50) values in the low micromolar
      range. Additional evidence shows that suramin inhibits RecA-catalysed proteolytic
      cleavage of the LexA repressor. The mechanism underlying such inhibitory actions
      of suramin involves its ability to disassemble RecA-single-stranded DNA
      filaments. Notably, suramin abolished ciprofloxacin-induced recA gene expression
      and the SOS response and augmented the bactericidal action of ciprofloxacin.
      CONCLUSIONS: Our findings suggest a strategy to chemically disrupt the vital
      processes controlled by RecA and hence the promise of small molecules for use
      against drug-susceptible as well as drug-resistant strains of M. tuberculosis for
      better infection control and the development of new therapies.

PMID- 24722838
TI  - Presence of HIV drug resistance in antiretroviral therapy-naive and -experienced
      patients from Papua New Guinea.
AB  - OBJECTIVES: The optimal benefits of antiretroviral therapy (ART) can be
      compromised by the emergence of HIV drug resistance (HIVDR) resulting in
      treatment failure. ART was introduced in Papua New Guinea (PNG) in 2004, yet
      biological data on HIVDR are lacking. The aim of the study was to investigate
      levels of HIVDR in ART-naive and -experienced patients in PNG. METHODS: We
      recruited, interviewed and collected blood from 108 ART-naive and 102 ART
      experienced patients from two Highlands provinces of PNG. Dried blood spots were
      tested for HIVDR from all patients with detectable plasma viral load of >=200
      copies/mL using established in-house assays. RESULTS: The PCR amplification
      success was 90.6% (n = 96) and 66.7% (n = 12) using dried blood spots from ART
      naive and -experienced patients, respectively. Transmitted drug resistance was
      detected in 2.1% (n = 2) of samples from ART-naive patients; acquired drug
      resistance was detected in 50% (n = 6) of samples from ART-experienced
      individuals. CONCLUSIONS: Our data showed that transmitted drug resistance in PNG
      is low and acquired drug resistance is higher with 12.7% of the ART-experienced
      patients failing treatment. As ART access is rapidly expanding in PNG, monitoring
      of drug resistance is paramount for early detection of treatment failure.

PMID- 24722839
TI  - Antimicrobial activity of a novel adhesive containing chlorhexidine gluconate
      (CHG) against the resident microflora in human volunteers.
AB  - OBJECTIVES: To evaluate the antimicrobial activity of a new, transparent
      composite film dressing, whose adhesive contains chlorhexidine gluconate (CHG),
      against the native microflora present on human skin. METHODS: CHG-containing
      adhesive film dressings and non-antimicrobial control film dressings were applied
      to the skin on the backs of healthy human volunteers without antiseptic
      preparation. Dressings were removed 1, 4 or 7 days after application. The
      bacterial populations underneath were measured by quantitative cultures (cylinder
      scrub technique) and compared with one another as a function of time. RESULTS:
      The mean baseline microflora recovery was 3.24 log10 cfu/cm(2). The mean log
      reductions from baseline measured from underneath the CHG-containing dressings
      were 0.87, 0.78 and 1.30 log10 cfu/cm(2) on days 1, 4 and 7, respectively,
      compared with log reductions of 0.67, -0.87 and -1.29 log10 cfu/cm(2) from
      underneath the control film dressings. There was no significant difference
      between the log reductions of the two treatments on day 1, but on days 4 and 7
      the log reduction associated with the CHG adhesive was significantly higher than
      that associated with the control adhesive. CONCLUSIONS: The adhesive containing
      CHG was associated with a sustained antimicrobial effect that was not present in
      the control. Incorporating the antimicrobial into the adhesive layer confers upon
      it bactericidal properties in marked contrast to the non-antimicrobial adhesive,
      which contributed to bacterial proliferation when the wear time was >=4 days.

PMID- 24722840
TI  - Detection of carbapenemase activity directly from blood culture vials using MALDI
      TOF MS: a quick answer for the right decision.
AB  - OBJECTIVES: Recently, matrix-assisted laser desorption ionization-time-of-flight
      mass spectrometry (MALDI-TOF MS) was successfully applied for the detection of
      carbapenemase activity directly from Gram-negative colonies. Based on this
      principle, we evaluated the performance of MALDI-TOF MS for rapid detection of
      carbapenemase activity directly from positive blood culture vials. METHODS: A
      total of 100 blood culture vials were randomly selected. MALDI-TOF MS
      carbapenemase assay results were confirmed by the detection of carbapenemase
      encoding genes. RESULTS: A total of 110 bacterial isolates were recovered. The
      MALDI-TOF MS carbapenemase assay identified 21 of 29 (72.4%) of the carbapenemase
      producing isolates directly from the blood culture vials, especially those
      encoding KPC-2 (100%) and SPM-1 (100%), after a 4 h incubation period. Although
      the majority of OXA-23-producing Acinetobacter baumannii isolates were not
      identified on day 1, all isolates were identified as carbapenemase producers
      directly from the colony on the next day. CONCLUSIONS: The MALDI-TOF MS
      carbapenemase assay is a feasible and rapid test to identify carbapenemase
      activity directly from blood culture vials. It may contribute to faster
      readjustment of empirical antimicrobial therapy and implementation of infection
      control measures.

PMID- 24722841
TI  - Plasma exchange significantly affects darunavir exposure.

PMID- 24722842
TI  - Evaluation of the pharmacodynamic profile of commonly used intravenous vancomycin
      dosing schemes in patients on automated peritoneal dialysis.
AB  - OBJECTIVES: The intent of this study was to evaluate the appropriateness of
      commonly used intravenous (iv) vancomycin dosing schemes in patients on automated
      peritoneal dialysis (APD) using population pharmacokinetic (PK) modelling and
      Monte Carlo simulation. METHODS: Data from a single-dose PK study of 10 non
      infected APD patients >=18 years old were analysed. Patients received iv
      vancomycin (15 mg/kg) followed by three cycler-assisted APD dwells over 8 h,
      followed by two 8 h dwells. Serum and dialysate samples were collected over the
      entire 24 h. A three-compartment model was fitted to the data with BigNPAG. Monte
      Carlo simulation was used to determine the probability of achieving an AUC/MIC
      ratio of >400 in both the serum and the peritoneal cavity for a variety of iv
      vancomycin dosing schemes (1-2 g every 24-48 h). RESULTS: In the probability of
      target attainment (PTA) analyses, only 2 g of iv vancomycin every 24 h conferred
      >90% probability of achieving an AUC/MIC ratio of >400 for MIC values <2 mg/L in
      the serum. However, this dosing regimen resulted in average trough concentrations
      >20 mg/L. In the peritoneal cavity, no regimen yielded PTA >=90% for MIC values
      >=0.5 mg/L. CONCLUSIONS: Although expert guidelines suggest iv vancomycin may be
      an acceptable empirical therapy for patients on APD with infection, these
      analyses indicate that iv vancomycin may not be effective for peritonitis but may
      be a viable option for non-peritoneal infections with MIC values <=1 mg/L.

PMID- 24722843
TI  - A 39-year-old male with upper back pain.

PMID- 24722844
TI  - Adolescent spontaneous pneumopericardium after playing table tennis.

PMID- 24722845
TI  - Periodontal disease with treatment reduces subsequent cancer risks.
AB  - AIM: The aim of our study was to evaluate the relationship between routine
      treatment of periodontal disease (PD) and the subsequent risks for cancers in
      Taiwan. METHODS: Study participants were selected from the Taiwan National Health
      Insurance (NHI) system database. The PD with a routine treatment cohort contained
      38 902 patients. For each treatment cohort participant, two age- and sex-matched
      comparison (control) cohort participants were randomly selected. Cox's
      proportional hazards regression analysis was used to estimate the effects of PD
      with treatment on the subsequent risk of cancer. RESULTS: The overall risk of
      developing cancer was significantly lower in the treatment cohort than in the
      patients without treatment (adjusted Hazard ratio = 0.72, 95% confidence interval
      = 0.68-0.76). The risks of developing most gastrointestinal tract, lung,
      gynecological and brain malignancies were significantly lower in the treatment
      cohort than in the comparison cohort. In contrast, the risks of prostate and
      thyroid cancers were significantly higher in the treatment cohort than in the
      comparison cohort. CONCLUSIONS: Our findings suggest that PD with treatment is
      associated with a significantly reduced overall risk of cancer and reduced risks
      of certain types of cancers.

PMID- 24722846
TI  - 'Time-to-amphotericin B' in cryptococcal meningitis in a European low-prevalence
      setting: analysis of diagnostic delays.
AB  - BACKGROUND: Cryptococcal meningitis is a rare disease in Europe, resulting in
      delayed recognition and slower initiation of specific treatment. AIM: To analyse
      the time-to-treatment and the factors that delay the diagnosis and treatment in
      the low-prevalence setting of a European centre. DESIGN: Retrospective review
      METHODS: We reviewed full medical records of all adult patients with cryptococcal
      meningitis referred to an HIV centre in Berlin, Germany in 10-year period between
      1st of October 2003 and 31st of September 2013. Multivariant statistics with
      bootstrap-resampling were performed. RESULTS: We identified 19 patients with a
      diagnosis of HIV-related cryptococcal meningitis (0.55% of all consecutive HIV
      infected patients). In almost half of our patients the diagnosis was not
      considered initially on admission to the secondary care centre and the first
      diagnostic clue being an accidental positive blood, cerebrospinal fluid or
      bronchoalveolar lavage culture growing Cryptococcus neoformans. The median time
      to-treatment was 5 days (range: 1-16). Known positive HIV status accelerated the
      time-to-diagnosis (p < 0.05) by a median of 1.89 days, whereas the CSF cell count
      <= 10/ul delayed diagnosis by a median time of 1.93 days (p < 0.1). CONCLUSIONS:
      Diagnostic delays could be avoided by encouraging practising physicians (i) to
      consider cryptococcal meningitis in immunosuppressed HIV-infected patients
      irrespective of neurological symptoms; (ii) to test for India ink, cryptococcal
      antigen and fungal cultures in immunosuppressed HIV-infected patients with normal
      CSF; (iii) to consider a possibility of underlying HIV infection in patients with
      unknown HIV status presenting with meningitis; and (iv) to consider early
      targeted HIV testing in persons at risk according to locally validated criteria.

PMID- 24722847
TI  - Exertional hypoxemia in stable COPD is common and predicted by circulating
      proadrenomedullin.
AB  - BACKGROUND: The prevalence of exertional hypoxemia in unselected patients with
      COPD is unknown. Intermittent hypoxia leads to adrenomedullin (ADM) upregulation
      through the hypoxia-inducible factor-1 pathway. We aimed to assess the prevalence
      and the annual probability to develop exertional hypoxemia in stable COPD. We
      also hypothesized that increased ADM might be associated with exertional
      hypoxemia and envisioned that adding ADM to clinical variables might improve its
      prediction in COPD. METHODS: A total of 1,233 6-min walk tests and circulating
      proadrenomedullin (proADM) levels from 574 patients with clinically stable,
      moderate to very severe COPD enrolled in a multinational cohort study and
      followed up for 2 years were concomitantly analyzed. RESULTS: The prevalence of
      exertional hypoxemia was 29.1%. In a matrix derived from a fitted-multistate
      model, the annual probability to develop exertional hypoxemia was 21.6%.
      Exertional hypoxemia was associated with greater deterioration of specific
      domains of health-related quality of life, higher severe exacerbation, and death
      annual rates. In the logistic linear and conditional Cox regression multivariable
      analyses, both FEV1% predicted and proADM proved independent predictors of
      exertional hypoxemia (P < .001 for both). Adjustment for comorbidities, including
      cardiovascular disorders, and exacerbation rate did not influence results.
      Relative to using FEV1% predicted alone, adding proADM resulted in a significant
      improvement of the predictive properties (P = .018). Based on the suggested
      nonlinear nomogram, patients with moderate COPD (FEV1% predicted = 50%) but high
      proADM levels (> 2 nmol/L) presented increased risk (> 30%) for exertional
      desaturation. CONCLUSIONS: Exertional desaturation is common and associated with
      poorer clinical outcomes in COPD. ADM improves prediction of exertional
      desaturation as compared with the use of FEV1% predicted alone. TRIAL REGISTRY:
      ISRCTN Register; No.: ISRCTN99586989; URL: www.controlled-trials.com.

PMID- 24722848
TI  - Managing protected areas under climate change: challenges and priorities.
AB  - The implementation of adaptation actions in local conservation management is a
      new and complex task with multiple facets, influenced by factors differing from
      site to site. A transdisciplinary perspective is therefore required to identify
      and implement effective solutions. To address this, the International Conference
      on Managing Protected Areas under Climate Change brought together international
      scientists, conservation managers, and decision-makers to discuss current
      experiences with local adaptation of conservation management. This paper
      summarizes the main issues for implementing adaptation that emerged from the
      conference. These include a series of conclusions and recommendations on
      monitoring, sensitivity assessment, current and future management practices, and
      legal and policy aspects. A range of spatial and temporal scales must be
      considered in the implementation of climate-adapted management. The adaptation
      process must be area-specific and consider the ecosystem and the social and
      economic conditions within and beyond protected area boundaries. However, a
      strategic overview is also needed: management at each site should be informed by
      conservation priorities and likely impacts of climate change at regional or even
      wider scales. Acting across these levels will be a long and continuous process,
      requiring coordination with actors outside the "traditional" conservation sector.
      To achieve this, a range of research, communication, and policy/legal actions is
      required. We identify a series of important actions that need to be taken at
      different scales to enable managers of protected sites to adapt successfully to a
      changing climate. 

PMID- 24722849
TI  - Lower limb ischaemia and reperfusion injury in healthy volunteers measured by
      oxidative and inflammatory biomarkers.
AB  - OBJECTIVE: Ischaemia-reperfusion (IR) injury is partly caused by the release of
      reactive oxygen species and cytokines and may result in remote organ injury.
      Surgical patients are exposed to surgical stress and anaesthesia, both of which
      can influence the IR response. An IR model without these interfering factors of
      surgery is, therefore, useful to test the potential of antioxidant and cytokine
      modulatory treatments. The aim of this study was to characterize a human
      ischaemia-reperfusion model with respect to oxidative and inflammatory
      biomarkers. MATERIALS AND METHODS: Ten male volunteers were exposed to 20 minutes
      of lower limb ischaemia. Muscle biopsies and blood samples were taken at baseline
      and 5, 15, 30, 60 and 90 minutes after tourniquet release and analysed for
      malondialdehyde (MDA), ascorbic acid, dehydroascorbic acid, tumor necrosis factor
      (TNF)-alpha, interleukin (IL)-1beta, IL-1 receptor antagonist (IL-1Ra), IL-6, IL
      10, TNF-receptor (TNF-R)I, TNF-RII and YKL-40. RESULTS: We found no significant
      increase in MDA in the muscle biopsies after reperfusion. Plasma levels of
      oxidative and pro- and anti-inflammatory parameters showed no significant
      differences between baseline and after reperfusion at any sampling time.
      CONCLUSION: Twenty minutes of lower limb ischaemia does not result in an
      ischaemia-reperfusion injury in healthy volunteers, measurable by oxidative and
      pro- and anti-inflammatory biomarkers in muscle biopsies and in the systemic
      circulation.

PMID- 24722850
TI  - Management and outcomes of coronary artery perforations during percutaneous
      treatment of acute coronary syndromes.
AB  - BACKGROUND: Coronary artery perforation (CAP) is an infrequent and life
      threatening complication of percutaneous coronary intervention (PCI), requiring
      prompt intervention. There is insufficient data about the prognosis and
      management of CAP in patients with acute coronary syndrome (ACS). The aim of this
      study was to investigate the management of CAP in patients with ACS. METHODS: The
      results of 25 patients with CAP were retrospectively analyzed. RESULTS: Of the 25
      patients, 14 patients (56%) had ACS. According to the Ellis classification, the
      grade of perforation was type-I in 8 (32%) patients, type-II in 6 (24%) patients
      and type-III in 11 (44%) patients. Prolonged balloon inflation was performed to
      20 (80%) cases of CAP. It successfully sealed the perforation in three cases of
      type-I, five cases of type-II CAP and in seven cases of type-III CAP. Seven
      patients underwent covered stent implantation. Emergent CABG was required in two
      patients with type-III CAP. In-hospital mortality was not observed in the
      patients. CONCLUSION: The outcomes of CAP in patients with ACS were similar to
      patients with stable coronary disease. The continuation of anti-platelet agents
      after the successful management of CAP may be encouraged in these patients.

PMID- 24722851
TI  - Vitamin D replacement therapy in patients with cardiac syndrome X.
AB  - AIMS: The aim of present study was to assess whether vitamin D, with proven
      beneficial effects on the cardiovascular system, has any effect on angina and
      exercise-induced ischemia in patients with cardiac syndrome X and low serum
      vitamin D. METHODS: Patients with cardiac syndrome X and low serum vitamin D3
      were studied before and after treatment with an intramuscular injection of
      vitamin D3 (300,000 units, every other week for 2 months). We determined the
      angina episode (per day) and several indices of exercise capacity. RESULTS: At
      the end of the treatment course (75+/-6 day), a significant increase of serum
      vitamin D3 occurred and was within the normal range (45+/-8 ng/ml) and the
      frequency of angina improved significantly (p=0.003). Exercise duration and
      maximal work capacity increased significantly (p<0.001). Maximal ST-segment
      depression (mm) decreased significantly (p=0.001). The calculated Duck treadmill
      score improved significantly (p=0.001). CONCLUSIONS: Our findings show that
      vitamin D replacement therapy in patients with cardiac syndrome X and vitamin D
      deficiency dramatically improves symptoms and signs of ischemia.

PMID- 24722852
TI  - Intracellular antibody immunity.
AB  - Antibodies allow the immune system to target pathogens despite their tremendous
      diversity and rapid evolution. Once bound to a pathogen, antibodies induce a
      broad range of effector mechanisms, including phagocytosis and complement.
      However, these mechanisms are all initiated in the extracellular space, meaning
      that pathogens like viruses evade them upon infection of their target cells.
      Recently, it has been shown that, in addition to mediating extracellular immune
      responses, antibodies also activate immunity inside infected cells. Antibodies
      that are bound to the surface of non-enveloped viruses or bacteria are carried
      into the cell during pathogen entry. Once inside the cell, these pathogen
      attached antibodies are recognised by a highly conserved, high affinity cytosolic
      antibody receptor called TRIM21. TRIM21 initiates both sensor and effector
      responses that reduce viral replication and induce an antiviral state. These
      responses are an important part of antiviral immunity and the removal of TRIM21
      results in uncontrolled viraemia and death in a mouse model of infection. 

PMID- 24722854
TI  - Mechanistic effects of IVIg in neuroinflammatory diseases: conclusions based on
      clinicopathologic correlations.
AB  - The mechanisms of action of IVIg on immunoregulatory and neuroinflammatory
      network have been predominantly based on in vitro experiments and animal studies,
      rather than direct effects on human tissues. Based on clinicopathologic
      correlations and tissues obtained before and after IVIg therapy, the better
      documented and clinically-relevant in-vivo actions of IVIg include effects on: a)
      Antibodies. An extracted antigen-specific anti-immunoglobulin (idiotypic)
      fraction appears partially responsible for its effect in myasthenia gravis and
      GBS; b) Complement. Sera from Dermatomyositis (DM) patients responding to IVIg,
      inhibit complement consumption and intercept MAC formation leading to
      disappearance of MAC deposits in the repeated muscle biopsies and normalization
      of muscle tissue; c) Genes. In repeated muscle biopsies from DM patients who
      improved after IVIg, but not from Inclusion-Body-Myositis (IBM) who did not
      improve, there is a 2-fold alteration of 2206 tissue genes associated with
      inflammation, fibrosis, tissue remodeling and regeneration; and d) degenerative
      proinflammatory molecules and beta-amyloid, implicated in neurodegenerative CNS
      diseases and IBM. In repeated muscle biopsies of IBM patients who did not respond
      to IVIg, the mRNA or protein expression for chemokines, IFN-gamma, TGF-beta, IL
      10, Ubiquitin and aB-crystallin is reduced, but not for the key molecules ICOS,
      ICOSL, IL-6, IL1-beta, perforin, APP, nitric oxide synthase and nitrotyrosine, in
      spite of good IVIg penetration in muscles. Collectively, the selective
      effectiveness of IVIg in human diseases seems to correlate in vivo with
      inhibition of causative inflammatory mediators. Study of accessible tissues
      before and after therapy and clinicopathologic correlations, may help explain the
      differential effect of IVIg in autoimmune or neuroinflammatory diseases. 

PMID- 24722853
TI  - Treatment of spinal cord injury with intravenous immunoglobulin G: preliminary
      evidence and future perspectives.
AB  - Neuroinflammation plays an important role in the secondary pathophysiological
      mechanisms of spinal cord injury (SCI) and can exacerbate the primary trauma and
      thus worsen recovery. Although some aspects of the immune response are
      beneficial, it is thought that leukocyte recruitment and activation in the acute
      phase of injury results in the production of cytotoxic substances that are
      harmful to the nervous tissue. Therefore, suppression of excessive inflammation
      in the spinal cord could serve as a therapeutic strategy to attenuate tissue
      damage. The immunosuppressant methylprednisolone has been used in the setting of
      SCI, but there are complications which have attenuated the initial enthusiasm.
      Hence, there is interest in other immunomodulatory approaches, such as
      intravenous Immunoglobulin G (IVIg). Importantly, IVIg is used clinically for the
      treatment of several auto-immune neuropathies, such as Guillain-Barre syndrome,
      chronic inflammatory demyelinating polyneuropathy (CIPD) and Kawasaki disease,
      with a good safety profile. Thus, it is a promising treatment candidate for SCI.
      Indeed, IVIg has been shown by our team to attenuate the immune response and
      result in improved neurobehavioral recovery following cervical SCI in rats
      through a mechanism that involves the attenuation of neutrophil recruitment and
      reduction in the levels of cytokines and cytotoxic enzymes Nguyen et al. (J
      Neuroinflammation 9:224, 2012). Here we review published data in the context of
      relevant mechanisms of action that have been proposed for IVIg in other
      conditions. We hope that this discussion will trigger future research to provide
      supporting evidence for the efficiency and detailed mechanisms of action of this
      promising drug in the treatment of SCI, and to facilitate its clinical
      translation. 

PMID- 24722855
TI  - Autosomal recessive agammaglobulinemia: the third case of Igbeta deficiency due
      to a novel non-sense mutation.
AB  - This study describes the third case worldwide of autosomal recessive
      agammaglobulinemia due to a novel non-sense mutation in Igbeta presenting with
      neutropenia, ecthyma and mild respiratory infections. 

PMID- 24722856
TI  - Screening and regulatory network analysis of survival-related genes of patients
      with colorectal cancer.
AB  - The purpose of this study was to screen key survival-related genes from patients
      with colorectal cancer and explore signal transduction network of the involved
      genes. In a previous study, survival-related genes of patients with colorectal
      cancer were selected by colorectal cancer-related expression data GSE17538 using
      the Significance Analysis of Microarrays (SAM3.01) software, and 235 genes
      related to the survival of patients with colorectal cancer were obtained.
      Therefore, the following screening and analysis were conducted on these 235 genes
      in this study. First, the enrichment analysis of transcription factor binding
      sites was conducted on the 235 genes. Genes with more than seven transcription
      factor binding sites were screened. Then, these genes and upregulated genes in
      colorectal cancer were intersected. Finally, survival analysis and regulatory
      network analysis were conducted on the screened genes. This allowed clarification
      of the relationship between these genes and the survival of patients with
      colorectal cancer and the signaling network involving these genes in the cell
      signal transduction network of colorectal cancer. Through the above analysis, six
      upregulated genes in colorectal cancer related to the survival of colorectal
      cancer patients and highly regulated by transcription factors were selected,
      namely STX2, PODXL, KLK6, GRB10, EHBP1 and CREB5. These genes are involved in
      signal regulatory networks related to colorectal cancer metastasis-related
      signaling pathways. Therefore, the survival of patients with colorectal cancer is
      closely correlated with colorectal cancer metastasis. The six survival-related
      genes affect the survival of patients by regulating colorectal cancer metastasis
      associated signaling pathways. 

PMID- 24722857
TI  - Characterization of functional domains of the cblD (MMADHC) gene product.
AB  - In humans vitamin B12 (cobalamin, Cbl) must be converted into two coenzyme forms,
      methylcobalamin (MeCbl) and adenosylcobalamin (AdoCbl), in order to maintain
      intracellular homeostasis of homocysteine and methylmalonic acid, respectively.
      Previously we have shown that in cblD patients three types of MMADHC mutations
      exist: 1) null mutations N-terminal to Met116 cause isolated methylmalonic
      aciduria (cblD-MMA) due to AdoCbl deficiency; 2) null mutations across the C
      terminus (p.Y140-R250) cause combined methylmalonic aciduria and homocystinuria
      (cblD-MMA/HC) due to AdoCbl and MeCbl deficiency; 3) missense mutations in a
      conserved C-terminal region (p.D246-L259) cause isolated homocystinuria (cblD-HC)
      due to MeCbl deficiency. To better understand the domain boundaries related to
      MeCbl formation, we made selected point mutations and C-terminal truncations in
      MMADHC and tested rescue of MeCbl and AdoCbl synthesis in immortalized cblD
      MMA/HC patient fibroblasts. Testing 20 mutations (15 missense and five C-terminal
      truncations) across p.P154-S287 revealed the presence of a region (p.R197-D226)
      responsible for MeCbl synthesis, which gave a similar cellular phenotype as cblD
      HC. Further, mutation of the polypeptide stretch between the new and patient
      defined regions (p.D226-D246) and directly C-terminal to the patient region
      (p.L259-R266), gave cellular phenotypes intermediate to those of cblD-HC and cblD
      MMA/HC. Finally, C-terminal truncation of more than 20 amino acids resulted in a
      cblD-MMA/HC like cellular phenotype, while truncation of between ten and 20 amino
      acids resulted in a cblD-HC like cellular phenotype. These data suggest that
      specific regions of MMADHC are involved in differential regulation of AdoCbl and
      MeCbl synthesis and help better define the boundaries of these regions. 

PMID- 24722858
TI  - Exploiting cancer genomics in pet animals to gain advantage for personalized
      medicine decisions.

PMID- 24722860
TI  - Appointment compliance among high risk newborns.

PMID- 24722859
TI  - Microbial diversity of landslide soils assessed by RFLP and SSCP fingerprints.
AB  - Landslides are a significant component of natural disasters in most countries
      around the world. Understanding these destructive phenomena through the analysis
      of possible correlations between microbial communities and the alteration of the
      soil responsible for landslides is important in order to reduce their negative
      consequences. To address this issue, bacterial and fungal communities in soils
      triggering landslides in Termini-Nerano and Massa Lubrense-Nerano (Naples, Italy)
      were analysed by genetic profiling techniques. Fingerprints were generated by
      single-strand conformation polymorphisms (SSCP) and random amplified polymorphic
      DNA (RAPD). The microbial community in both soil types was enriched in species
      which could contribute to the degradation process occurring during landslides,
      forming biofilms and leading to the transformation or the formation of minerals.
      Indeed, some of the identified bacteria were found to favour the transformation
      of clay minerals. These findings suggest a possible relationship between
      bacterial and fungal community-colonising soils and the occurrence of landslides.

PMID- 24722861
TI  - Use of CPAP and surfactant therapy in newborns with respiratory distress
      syndrome.
AB  - Respiratory distress syndrome (RDS) is a major disease burden in the developing
      countries. Current evidence supports early continuous positive airway pressure
      (CPAP) use and early selective surfactant administration as the most efficacious
      interventions in the management of RDS, both in developed and developing
      countries. In developing countries, it is recommended to increase institutional
      deliveries and increase the coverage of antenatal steroids in women in preterm
      labor as preventive measures. Establishing intervention of CPAP and surfactant
      therapies in the Level II special care newborn units (SCNUs) and Level III units
      requires focus on training nursing staff and pediatricians across the board.
      These approaches would pave the way in optimizing the care of the preterm infants
      with RDS and decrease their mortality and morbidity significantly. 

PMID- 24722862
TI  - On farm production of arbuscular mycorrhizal fungi inoculum using lignocellulosic
      agrowastes.
AB  - The present study evaluated the efficiency of lignocellulosic agrowastes produced
      in Brazil as substrates for production of on farm AMF inoculum and tested
      different diluents and inoculation techniques. In a first experiment, Sorghum
      bicolor seedlings were colonized with Rhizophagus clarus or Claroideoglomus
      etunicatus and transplanted to 20 L bags containing sugarcane bagasse (SC), king
      palm leaf sheets (KP), or barley hulls (BH) mixed (1:1:1 or 2:1:1, v/v/v) with
      sand and rice shell. SC and KP were conducive for production of spores and
      infectious propagules. A number of infectious propagules obtained were greater
      than with BH and ranged from 233-350 propagules cm(-3) for both isolates in SC
      and KP at the1:1:1 mix dilution. Number of spores of both fungi was affected
      mainly by the SC agrowaste, and spore densities were significantly higher
      compared to KP and BH. In a second experiment, SC was mixed with soil or sand and
      inoculation consisted of transplanting colonized seedlings or adding soil
      inoculum. Number of propagules tended to differ for each fungus according to the
      inoculation technique or diluent. It is concluded from the data that SC and KP
      are suitable agrowastes to be incorporated in substrates for producing AMF
      inoculum using the on farm method. 

PMID- 24722863
TI  - The Role of Total Parotidectomy for Metastatic Cutaneous Squamous Cell Carcinoma
      and Malignant Melanoma.
AB  - IMPORTANCE: Metastatic cutaneous malignancies of the head and neck, including
      cutaneous squamous cell carcinoma (cSCC) and malignant melanoma (MM), are
      aggressive cancers frequently involving the parotid-area lymph nodes (LNs). In
      such cases, controversy exists about the extent of surgical resection, with many
      centers choosing not to remove the parotid deep lobe LNs. OBJECTIVES: To
      determine patterns of intraparotid and neck metastasis, to identify risk factors,
      and to report outcomes in patients with parotid superficial lobe LN metastasis
      from cSCC and MM. DESIGN, SETTING, AND PARTICIPANTS: We retrospectively reviewed
      65 adults from Mayo Clinic in Minnesota who underwent total parotidectomy and
      neck dissection for metastatic cSCC (n = 42) or MM (n = 23) involving the parotid
      superficial lobe. INTERVENTIONS: Total parotidectomy and neck dissection. MAIN
      OUTCOMES AND MEASURES: The presence and number of parotid deep lobe and neck LNs
      involved with metastatic disease were assessed. Risk factors associated with
      metastatic spread to the parotid deep lobe were identified, and patient outcomes
      are reported. RESULTS: Eleven of 42 patients with cSCC (26%) and 3 of 23 patients
      with MM (13%) metastatic to the parotid superficial lobe also had parotid deep
      lobe metastasis. Thirteen of 42 patients with cSCC (31%) and 6 of 23 patients
      with MM (26%) had positive cervical LN metastasis. Among all patients, 22% (14 of
      65) had metastasis to the parotid deep lobe, and 29% (19 of 65) had metastasis to
      cervical LNs. By univariate analysis, neck metastasis and N2 neck disease were
      risk factors for metastatic cSCC spread to the parotid deep lobe. Parotid-area
      local control was excellent in patients with metastatic cSCC (93% [39 of 42]) and
      MM (100% [23 of 23]). Long-term survival remains poor because distant metastases
      are common. CONCLUSIONS AND RELEVANCE: Metastatic cSCC and MM to the parotid
      superficial lobe also involve LNs in the parotid deep lobe and neck in a
      significant and almost equal number of patients. Parotid deep lobe metastasis
      from cutaneous malignancies portends a poor prognosis. Therefore, patients with
      superficial parotid gland metastasis should be considered for management with not
      only neck dissection and adjuvant therapy but also deep lobe parotidectomy.

PMID- 24722864
TI  - Prevention of incisional hernia in midline laparotomy with onlay mesh: a
      randomized clinical trial.

PMID- 24722865
TI  - Disclosure of surgeon experience.
AB  - It is uncertain whether there is an ethical obligation to disclose surgical
      experience. This article explores the impact of principles including respect for
      patient autonomy, nonmaleficence, and justice, as well as professional duties
      including truth-telling on the decision-making relevant to the process of
      informed consent, taking into account surgeon experience, training, and the
      expected risk and uncertainty surrounding the disease process and operation.
      Issues such as the integrity of the doctor-patient relationship, difficulties
      with access to complex surgical services, and limitations in applying statistics
      to the future outcomes of individual surgeons are explored. 

PMID- 24722866
TI  - Should we routinely transfuse platelet for immune thrombocytopenia patients with
      platelet count less than 10 * 109/L who underwent laparoscopic splenectomy?
AB  - BACKGROUND: Laparoscopic splenectomy (LS) is considered as the gold standard
      procedure for patients with immune thrombocytopenia (ITP). In many institutions,
      platelet counts less than 10 * 10(9)/L contraindicate LS. OBJECTIVE: This study
      aimed to investigate the safety and feasibility of LS for ITP patients with
      platelet counts less than 10 * 10(9)/L. METHODS: A total of 88 cases of LS were
      performed for ITP patients from June 2010 to December 2012. The patients were
      prospectively divided into three groups based on their immediate preoperative
      platelet count: < 10 * 10(9)/L (group 1); 10 * 10(9)/L to 30 * 10(9)/L (group 2);
      and > 30 * 10(9)/L (group 3). We collected the patients' demographic
      characteristics, perioperative details, and platelet count response to surgery.
      RESULTS: The patients in the three groups had comparable demographic
      characteristics. Only one patient in group 1 required conversion (2.4 %). The
      patients in group 1 experienced more blood loss than those in group 3, but this
      was not statistically significant. There were no significant differences between
      group 2 and group 3 in terms of operating time and blood loss. No statistically
      significant differences were found between the three groups with regard to
      complications and postoperative hospital stay. CONCLUSIONS: It is safe and
      feasible to perform LS in ITP patients with platelet count less than 10 *
      10(9)/L, without platelet transfusion. The indication for platelet transfusion
      during LS for ITP patients should be the bleeding manifestations due to
      thrombocytopenia other than low platelet count itself.

PMID- 24722867
TI  - The extent of surgical patients' understanding.
AB  - The notion that consent to surgery must be informed implies not only that
      information should be provided by the surgeon but also that the information
      should be understood by the patient in order to give a foundation to his or her
      decision to accept or refuse treatment and thus, achieve autonomy for the
      patient. Nonetheless, this seems to be an idyllic situation, since most patients
      do not fully understand the facts offered and thus the process of surgical
      informed consent, as well as the patient's autonomy, may be jeopardized. Informed
      consent does not always mean rational consent. 

PMID- 24722868
TI  - [Cytoreductive surgery for malignant peritoneal tumors].
AB  - Cytoreductive surgery is an essential part of a multimodality treatment concept
      for peritoneal metastases. Indications are primary peritoneal tumors like
      peritoneal mesothelioma or secondaries from colorectal cancer or pseudomyxoma
      peritonei. Patients with gastric or ovarian carcinoma or abdominal sarcoma with
      peritoneal seedings can be treated within studies. Tumor entity, tumor load, and
      tumor distribution are the most critical issues for patient selection. Complete
      macroscopic cytoreduction is the strongest prognostic factor and can be achieved
      by parietal and visceral peritonectomy. The operation should be performed in a
      standardized manner. Due to possible tumor manifestation in all four quadrants of
      the abdomen and extensive extraperitoneal dissection, extensive surgical and
      oncological expertise is prerequisite. Treatment in specialized surgical oncology
      centers is recommended to minimize morbidity and mortality. The German Society
      for General and Visceral Surgery is certifying centers of competence for surgical
      treatment of peritoneal malignancies. Data of all patients are documented in the
      HIPEC register. The inclusion of patients in studies is recommended. 

PMID- 24722869
TI  - [Use of fibrin sealant to reduce pain and postoperative impairment at the split
      skin graft donor site].

PMID- 24722870
TI  - [B-lymphocytes as effectors and regulators in systemic lupus erythematosus].

PMID- 24722871
TI  - The origin of high activity but low CO(2) selectivity on binary PtSn in the
      direct ethanol fuel cell.
AB  - The most active binary PtSn catalyst for direct ethanol fuel cell applications
      has been studied at 20  degrees C and 60  degrees C, using variable temperature
      electrochemical in situ FTIR. In comparison with Pt, binary PtSn inhibits ethanol
      dissociation to CO(a), but promotes partial oxidation to acetaldehyde and acetic
      acid. Increasing the temperature from 20  degrees C to 60  degrees C facilitates
      both ethanol dissociation to CO(a) and then further oxidation to CO2, leading to
      an increased selectivity towards CO2; however, acetaldehyde and acetic acid are
      still the main products. Potential-dependent phase diagrams for surface oxidants
      of OH(a) formation on Pt(111), Pt(211) and Sn modified Pt(111) and Pt(211)
      surfaces have been determined using density functional theory (DFT) calculations.
      It is shown that Sn promotes the formation of OH(a) with a lower onset potential
      on the Pt(111) surface, whereas an increase in the onset potential is found upon
      modification of the (211) surface. In addition, Sn inhibits the Pt(211) step edge
      with respect to ethanol C-C bond breaking compared with that found on the pure
      Pt, which reduces the formation of CO(a). Sn was also found to facilitate ethanol
      dehydrogenation and partial oxidation to acetaldehyde and acetic acid which,
      combined with the more facile OH(a) formation on the Pt(111) surface, gives us a
      clear understanding of the experimentally determined results. This combined
      electrochemical in situ FTIR and DFT study provides, for the first time, an
      insight into the long-term puzzling features of the high activity but low CO2
      production found on binary PtSn ethanol fuel cell catalysts. 

PMID- 24722872
TI  - Efficient Kill-Save Ratios Ease Up the Cognitive Demands on Counterintuitive
      Moral Utilitarianism.
AB  - The dual-process model of moral judgment postulates that utilitarian responses to
      moral dilemmas (e.g., accepting to kill one to save five) are demanding of
      cognitive resources. Here we show that utilitarian responses can become
      effortless, even when they involve to kill someone, as long as the kill-save
      ratio is efficient (e.g., 1 is killed to save 500). In Experiment 1, participants
      responded to moral dilemmas featuring different kill-save ratios under high or
      low cognitive load. In Experiments 2 and 3, participants responded at their own
      pace or under time pressure. Efficient kill-save ratios promoted utilitarian
      responding and neutered the effect of load or time pressure. We discuss whether
      this effect is more easily explained by a parallel-activation model or by a
      default-interventionist model.

PMID- 24722873
TI  - Synthesis of thiolated Ag/Au bimetallic nanoclusters exhibiting an anti-galvanic
      reduction mechanism and composition-dependent fluorescence.
AB  - We report a direct one-pot approach, employing 11-mercaptoundecanoic acid (11
      MUA) as a reducing and capping agent, for the preparation of fluorescent Ag/Au
      bimetallic nanoclusters (Ag/AuNCs) from HAuCl4 and AgNO3 in basic aqueous
      solution at room temperature. Unlike the monocomponent 11-MUA-AgNCs with
      negligible fluorescence, the as-prepared 11-MUA-Ag/AuNCs exhibit similar average
      diameters of ~1.8 nm but much stronger and tunable fluorescence by varying the
      concentration ratios of AgNO3 to HAuCl4 in the synthesis. The quantum yield of
      the 11-MUA-Ag/AuNCs can reach 6.81% at a Ag-to-Au molar ratio of 1 : 2, nearly 3
      fold higher than the monocomponent 11-MUA-AuNCs (2.38%) of similar sizes. More
      importantly, the occurrence of the reaction between Ag(+) ions and Au(0) of 11
      MUA-AuNCs (which is opposite to the classic galvanic theory) and the coexistence
      of Ag(0) and Au(+) in the final NC products, are revealed by thorough analysis of
      XPS data. The anti-galvanic reduction, that is, metal ions are replaced by less
      reactive metals, has been further demonstrated through the reaction between the
      as-obtained purified monocomponent 11-MUA-AuNCs and Ag(+) ions. Direct
      electrochemical insights into the anti-galvanic reduction mechanism were provided
      by cyclic voltammetry characterizations of the NCs, and the universality of the
      anti-galvanic reduction was tested by preparing thiolated Pt/Au bimetallic NCs
      using platinum instead of silver in our synthetic system. 

PMID- 24722874
TI  - A real-time characterization method to rapidly optimize molecular beacon signal
      for sensitive nucleic acids analysis.
AB  - This research demonstrates an integrated microfluidic titration assay to
      characterize the cation concentrations in working buffer to rapidly optimize the
      signal-to-noise ratio (SNR) of molecular beacons (MBs). The "Microfluidic Droplet
      Array Titration Assay" (MiDATA) integrated the functions of sample dilution,
      sample loading, sample mixing, fluorescence analysis, and re-confirmation
      functions all together in a one-step process. It allows experimentalists to
      arbitrarily change sample concentration and acquire SNR measurements
      instantaneously. MiDATA greatly reduces sample dilution time, number of samples
      needed, sample consumption, and the total titration time. The maximum SNR of
      molecular beacons is achieved by optimizing the concentrations of the monovalent
      and divalent cation (i.e., Mg(2+) and K(+)) of the working buffer. MiDATA
      platform is able to reduce the total consumed reagents to less than 50 MUL, and
      decrease the assay time to less than 30 min. The SNR of the designated MB is
      increased from 20 to 126 (i.e., enhanced the signal 630 %) using the optimal
      concentration of MgCl2 and KCl determined by MiDATA. This novel microfluidics
      based titration method is not only useful for SNR optimization of molecular
      beacons but it also can be a general method for a wide range of fluorescence
      resonance energy transfer (FRET)-based molecular probes.

PMID- 24722875
TI  - Automated quantum mechanical total line shape fitting model for quantitative NMR
      based profiling of human serum metabolites.
AB  - An automated quantum mechanical total line shape (QMTLS) fitting model was
      implemented for quantitative nuclear magnetic resonance (NMR)-based profiling of
      42 metabolites in ultrafiltrated human serum samples. Each metabolite was
      described by a set of chemical shifts, J-couplings, and line widths. These
      parameters were optimized for each metabolite in each sample by iteratively
      minimizing the difference between the calculated and the experimental spectrum.
      In total, 92.0 to 98.1 % of the signal intensities in the experimental spectrum
      could be explained by the calculated spectrum. The model was validated by
      comparison to signal integration of metabolites with isolated signals and by
      means of standard additions. Metabolites present at average concentration higher
      than 50 MUM were quantified with average absolute relative error less than 10 %
      when using different initial parameters for the fitting procedure. Furthermore,
      the biological applicability of the QMTLS model was demonstrated on 287 samples
      from an intervention study in 37 human volunteers undergoing an exercise
      challenge. Our automated QMTLS model was able to cope with the large dynamic
      range of metabolite concentrations in serum and proved to be suitable for high
      throughput analysis.

PMID- 24722876
TI  - Multi-analytical platform metabolomic approach to study miltefosine mechanism of
      action and resistance in Leishmania.
AB  - Miltefosine (MT) (hexadecylphosphocholine) was implemented to cope with
      resistance against antimonials, the classical treatment in Leishmaniasis. Given
      the scarcity of anti- Leishmania (L) drugs and the increasing appearance of
      resistance, there is an obvious need for understanding the mechanism of action
      and development of such resistance. Metabolomics is an increasingly popular tool
      in the life sciences due to it being a relatively fast and accurate technique
      that can be applied either with a particular focus or in a global manner to
      reveal new knowledge about biological systems. Three analytical platforms, gas
      chromatography (GC), liquid chromatography (LC) and capillary electrophoresis
      (CE) have been coupled to mass spectrometry (MS) to obtain a broad picture of
      metabolic changes in the parasite. Impairment of the polyamine metabolism from
      arginine (Arg) to trypanothione in susceptible parasites treated with MT was in
      some way expected, considering the reactive oxygen species (ROS) production
      described for MT. Importantly, in resistant parasites an increase in the levels
      of amino acids was the most outstanding feature, probably related to the
      adaptation of the resistant strain for its survival inside the parasitophorous
      vacuole. 

PMID- 24722877
TI  - Detection of follicular transport of lidocaine and metabolism in adipose tissue
      in pig ear skin by DESI mass spectrometry imaging.
AB  - Desorption electrospray ionization (DESI) mass spectrometry imaging is
      demonstrated as a detection technique for penetration experiments of drugs in
      skin. Lidocaine ointment was used as the model compound in ex vivo experiments
      with whole pig ears as the skin model. Follicular transport of lidocaine into the
      deeper skin layers is demonstrated for the first time. Furthermore, metabolism of
      lidocaine to 3-OH-lidocaine was observed in subcutaneous tissue as well as in
      lobules of white adipose tissue surrounding the hair follicles. These results
      suggest that it is advantageous to use full thickness skin, including
      subcutaneous tissue, for skin metabolism studies. 

PMID- 24722879
TI  - Thrombosis prophylaxis and mortality risk among critically ill adults.
AB  - BACKGROUND: The optimal approach for managing increased risk of VTE among
      critically ill adults is unknown. METHODS: An observational study of 294,896
      episodes of critical illness among adults was conducted in 271 geographically
      dispersed US adult ICUs. The primary outcomes were all-cause ICU and in-hospital
      mortality after adjustment for acuity and other factors among groups of patients
      assigned, based on clinical judgment, to prophylactic anticoagulation, mechanical
      devices, both, or neither. Outcomes of those managed with prophylactic
      anticoagulation or mechanical devices were compared in a separate paired,
      propensity-matched cohort. RESULTS: After adjustment for propensity to receive
      VTE prophylaxis, APACHE (Acute Physiology and Chronic Health Evaluation) IV
      scores, and management with mechanical ventilation, the group treated with
      prophylactic anticoagulation was the only one with significantly lower risk of
      dying than those not provided VTE prophylaxis (ICU, 0.81 [95% CI, 0.79-0.84];
      hospital, 0.84 [95% CI, 0.82-0.86; P < .0001). The mortality risk of those
      receiving mechanical device prophylaxis was not lower than that of patients
      without VTE prophylaxis. A study of 87,107 pairs of patients matched for
      propensity to receive VTE prophylaxis found that those managed with prophylactic
      anticoagulation therapy had significantly lower risk of death (ICU subhazard
      ratio, 0.82 [95% CI, 0.78-0.85]; hospital subhazard ratio, 0.82 [95% CI, 0.79
      0.85]; P < .001) than those receiving only mechanical device prophylaxis.
      CONCLUSIONS: These findings support a recommendation for prophylactic
      anticoagulation therapy in preference to mechanical device prophylaxis for
      critically ill adult patients who do not have a contraindication to
      anticoagulation.

PMID- 24722878
TI  - Microfluidic device (ExoChip) for on-chip isolation, quantification and
      characterization of circulating exosomes.
AB  - Membrane bound vesicles, including microvesicles and exosomes, are secreted by
      both normal and cancerous cells into the extracellular space and in blood
      circulation. These circulating extracellular vesicles (cirEVs) and exosomes in
      particular are recognized as a potential source of disease biomarkers. However,
      to exploit the use of circulatory exosomes as a biomarker, a rapid, high
      throughput and reproducible method is required for their isolation and molecular
      analysis. We have developed a simple, low cost microfluidic-based platform to
      isolate cirEVs enriched in exosomes directly from blood serum allowing
      simultaneous capture and quantification of exosomes in a single device. To
      capture specific exosomes, we employed "ExoChip", a microfluidic device
      fabricated in polydimethylsiloxane (PDMS) and functionalized with antibodies
      against CD63, an antigen commonly overexpressed in exosomes. Subsequent staining
      with a fluorescent carbocyanine dye (DiO) that specifically labels the exosomes,
      we quantitated exosomes using a standard plate-reader. Ten independent ExoChip
      experiments performed using serum obtained from five pancreatic cancer patients
      and five healthy individuals revealed a statistically significant increase (2.34
      +/- 0.31 fold, p < 0.001) in exosomes captured in cancer patients when compared
      to healthy individuals. Exosomal origins of ExoChip immobilized vesicles were
      further confirmed using immuno-electron-microscopy and Western blotting. In
      addition, we demonstrate the ability of ExoChip to recover exosomes with intact
      RNA enabling profiling of exosomal-microRNAs through openarray analysis, which
      has potential applications in biomarker discovery. Based on our findings, ExoChip
      is a well suited platform to be used as an exosome-based diagnostic and research
      tool for molecular screening of human cancers. 

PMID- 24722880
TI  - Identifying and quantifying multisensory integration: a tutorial review.
AB  - We process information from the world through multiple senses, and the brain must
      decide what information belongs together and what information should be
      segregated. One challenge in studying such multisensory integration is how to
      quantify the multisensory interactions, a challenge that is amplified by the host
      of methods that are now used to measure neural, behavioral, and perceptual
      responses. Many of the measures that have been developed to quantify multisensory
      integration (and which have been derived from single unit analyses), have been
      applied to these different measures without much consideration for the nature of
      the process being studied. Here, we provide a review focused on the means with
      which experimenters quantify multisensory processes and integration across a
      range of commonly used experimental methodologies. We emphasize the most commonly
      employed measures, including single- and multiunit responses, local field
      potentials, functional magnetic resonance imaging, and electroencephalography,
      along with behavioral measures of detection, accuracy, and response times. In
      each section, we will discuss the different metrics commonly used to quantify
      multisensory interactions, including the rationale for their use, their
      advantages, and the drawbacks and caveats associated with them. Also discussed
      are possible alternatives to the most commonly used metrics. 

PMID- 24722881
TI  - Circumferential dynamic stabilization of the lumbar spine: a biomechanical
      analysis.
AB  - PURPOSE: To assess segmental angulation and mobility following implantation of
      the Charite artificial disc in combination with the posterior dynamic fixation
      device dynamic stabilization system (DSS) and the interspinous spacer Coflex at
      the L4-L5 segment, respectively. METHODS: Six human L4-L5 specimens were loaded
      with pure moments of +/-7.5 Nm in flexion/extension, lateral bending, and axial
      rotation in a custom-made spine tester. The testing protocol was as follows: (a)
      intact condition, (b) destabilization by resection of the anterior longitudinal
      ligament (ALL), (c) implantation of the Charite with retained posterior
      longitudinal ligament (PLL), (d) supplemental DSS implantation, (e) removal of
      DSS rods and PLL resection, (f) DSS rod re-implantation, (g) enlargement of rod
      length, and (h) removal of DSS and implantation of Coflex. Range of motion (ROM),
      neutral zone, and segmental angulation were determined. RESULTS: ALL resection
      did not influence significantly ROM. TDR increased lateral bending and axial
      rotation only after resection of the PLL, whereas flexion/extension remained
      unchanged. DSS limited all degrees of freedom prior to and after PLL resection.
      Rod length enlargement had no significant effect. Coflex limited significantly
      flexion/extension compared to the intact state and TDR, whereas lateral bending
      and axial rotation remained unchanged. TDR increased lordosis, whereas Coflex had
      a substantial kyphosing effect. CONCLUSIONS: This study demonstrates that
      posterior dynamic stabilization in combination with TDR reduces flexion/extension
      ROM and segmental lordosis in a monosegmental biomechanical model.

PMID- 24722882
TI  - Floating spine after pedicle subtraction osteotomy for post-traumatic kyphosis.
AB  - PURPOSE: Pedicle subtraction osteotomy (PSO) was developed to achieve significant
      correction of a deformity. It was initially used to correct sagittal plane
      deformities associated with ankylosing spondylitis, but recently it has also been
      performed in patients with post-traumatic kyphosis. Our aim was to report a case
      of a floating spine after PSO for post-traumatic kyphosis. METHODS: A 50-year-old
      man was injured after a fall. He had a compression fracture at T12 and an open
      fracture of the right lower limb. Although he presented with focal back pain, his
      open fracture was treated first by surgical intervention. The T12 compression
      fracture was treated conservatively. One year later, he had lower limb numbness
      and muscle weakness. His imaging demonstrated focal kyphosis on T12 and spinal
      cord compression. The diagnosis was post-traumatic kyphosis, which was treated
      with PSO. We performed osteotomy at T12, discectomy and bone graft at T11-T12,
      and posterior fusion from T10 to L2. RESULTS: One year after PSO, we removed the
      instruments because he complained of pain around them and found complete bony
      union between T11 and T12. He immediately experienced worse pain and could not
      walk or stand for more than 10 min. Imaging showed a floating spine between T12
      and L1. He underwent anterior fusion at T12-L1, after which his severe back pain
      disappeared. CONCLUSIONS: This case points out a pitfall of PSO. Although it is a
      powerful tool for correcting an imbalanced spine, we should recognize its
      pitfalls and try to avoid them.

PMID- 24722883
TI  - Inhibitory potential of naphthoquinones leached from leaves and exuded from roots
      of the invasive plant Impatiens glandulifera.
AB  - Exploring the effects of allelopathic plant chemicals on the growth of native
      vegetation is essential to understand their ecological roles and importance in
      exotic plant invasion. Naphthoquinones have been identified as potential growth
      inhibitors produced by Impatiens glandulifera, an exotic annual plant that
      recently invaded temperate forests in Europe. However, naphthoquinone release and
      inhibitory potential have not been examined. We quantified the naphthoquinone
      content in cotyledons, leaves, stems, and roots from plants of different ages of
      both the invasive I. glandulifera and native Impatiens noli-tangere as well as in
      soil extracts and rainwater rinsed from leaves of either plant species by using
      ultra-high pressure liquid chromatography-mass spectrometry (UHPLC-MS). We
      identified the compound 2-methoxy-1,4-naphthoquinone (2-MNQ) exclusively in plant
      organs of I. glandulifera, in resin bags buried into the soil of patches invaded
      by I. glandulifera, and in rainwater rinsed from its leaves. This indicates that
      2-MNQ is released from the roots of I. glandulifera and leached from its leaves
      by rain. Specific bioassays using aqueous shoot and root extracts revealed a
      strong inhibitory effect on the germination of two native forest herbs and on the
      mycelium growth of three ectomycorrhiza fungi. These findings suggest that the
      release of 2-MNQ may contribute to the invasion success of I. glandulifera and
      support the novel weapons hypothesis. 

PMID- 24722884
TI  - Double jeopardy: metabolic syndrome leads to increased sedentary behavior in peri
      pubertal minority females.
AB  - While most studies have focused on investigating the preventive effects of
      physical activity on metabolic risk, the longitudinal impacts of metabolic
      syndrome (MetS) on activity levels is poorly understood. This study aims to
      examine the influence of MetS on initial activity levels and the trajectory of
      activity levels in Latina and African American female children over 12 months (n
      = 55, 9 +/- 1 years). Metabolic measures, including fat and lean tissue mass by
      BodPod, fasting glucose, lipids, blood pressure, and waist circumference, were
      collected at baseline. Moderate-to-vigorous physical activity and sedentary
      behavior by accelerometry were collected on a quarterly basis. There were no
      significant differences in either initial activity levels by MetS status
      (Moderate-to-vigorous physical activity: 33 +/- 12 mins/day for MetS, 48 +/- 28
      mins/day for Non-MetS, p = .12; sedentary behavior: 408 +/- 57 mins/day for MetS,
      421 +/- 72 mins/day for Non-MetS, p = .67). Longitudinal declines in moderate-to
      vigorous physical activity (p = .038) and increases in sedentary behavior (p =
      .003) were found. Daily sedentary behavior increased by 82.64 more minutes in
      youth with MetS than in those without over one year (p = .015). This study yields
      the first evidence of the adverse effect of MetS on sedentary behavior. Targeted
      intervention strategies to reduce progressive sedentariness evident in minority
      youth with MetS are warranted. 

PMID- 24722885
TI  - Prognostic impact of completion of initial high-dose methotrexate therapy on
      primary central nervous system lymphoma: a single institution experience.
AB  - BACKGROUND: This retrospective single-center study assessed the feasibility,
      outcomes, and side-effects of high-dose methotrexate (HD-MTX) plus procarbazine
      in the treatment of immunocompetent patients with primary central nervous system
      lymphoma (PCNSL). METHODS: Ninety-one patients diagnosed with PCNSL between
      January 2001 and December 2011 were treated with HD-MTX plus procarbazine. To
      reduce neurotoxicity in patients aged >=60 years, only those not responding to
      chemotherapy and patients with relapse underwent whole-brain irradiation.
      RESULTS: All 91 consecutive patients were scheduled to receive HD-MTX. Their
      median age was 66 years (range 32-88 years) and their median Karnofsky
      performance score was 40 (range 20-100). While 56 patients (61.5 %) completed 3
      cycles of HD-MTX chemotherapy and 48 (52.7 %) showed a complete response,
      treatment was stopped in 11 patients (12.1 %) due to toxicity. The median overall
      survival and progression-free survival were 40.6 and 11.7 months, respectively.
      Overall survival was significantly improved in patients who completed 3 cycles of
      chemotherapy compared with those did not (56.4 vs 24.0 months; p = 0.013 by
      univariate and p = 0.022 by multivariate analysis). CONCLUSIONS: Initial
      treatment with HD-MTX plus procarbazine was effective in patients with PCNSL.
      Completion of 3 cycles of HD-MTX chemotherapy was a significant independent
      prognostic factor for patient survival.

PMID- 24722886
TI  - External validation of existing nomograms predicting lymph node metastases in
      cystectomized patients.
AB  - OBJECTIVES: Karakiewicz et al. and Green et al. created pre-cystectomy nomograms
      to predict lymph node involvement. The aim of the study was to externally
      validate these two nomograms in intermediate-volume institutions in Europe.
      PATIENTS AND METHODS: Data from a Serbian single-centre cystectomy series
      comprising 183 patients with bladder cancer were used for the validation of two
      US nomograms, which were originally based on data from 726 and 201 patients,
      respectively. A multivariate regression model assessed the value of the clinical
      parameters integrated in the two nomograms. The expected predictive accuracy,
      calibration and clinical utility according to the nomograms were calculated.
      RESULTS: Comparison of our dataset with the previously published data shows
      differences in nearly all underlying risk variables. Overall, 109 (59.6 %)
      patients had lymph node metastases. The analysis demonstrated that hydronephrosis
      and status of lymph nodes on computed tomography have independent prognostic
      value. The performance of the nomograms deteriorated from the development set,
      and the predictive accuracies for the two models showed moderate discriminatory
      ability (61.2-69.1 %). In the decision curve analysis, only the Green et al.
      model predicting lymph node positivity provided net benefit. CONCLUSIONS: The
      Green et al. nomogram seems applicable to patients from Europe, despite varying
      risk factors in the validation dataset. Acceptance of such a tool into daily
      clinical management may lead to more appropriate decision-making. Nevertheless,
      further improvement and implementation of novel statistical models with enhanced
      predictive accuracy is needed.

PMID- 24722887
TI  - Estramustine phosphate sodium in heavily pretreated patients with metastatic
      breast cancer: a retrospective consecutive case series.
AB  - BACKGROUND: Estramustine phosphate sodium (EMP) is an oral agent poorly developed
      -although active--in patients with metastatic breast cancer (MBC). To resume
      interest in EMP in MBC, we analyzed a retrospective series of consecutive
      patients with estrogen receptor-positive disease. METHODS: EMP was given orally
      at a dose of 140 mg daily. Treatment discontinuation rates due to progressive
      disease/toxicity and response rates were assessed. RESULTS: Twenty postmenopausal
      patients with mainly visceral disease were treated with EMP, in five cases in
      combination with other anticancer drugs. Median numbers of previous
      chemotherapies and hormonal treatments were six and four, respectively. From the
      entire cohort, one complete response and four partial responses were observed.
      The proportions of patients free of progression at 6 and 12 months were 39 and 8
      %, respectively. Six patients discontinued EMP, three each for toxicity and
      adverse events. CONCLUSION: Good disease control was obtained in heavily
      pretreated MBC patients receiving EMP. Toxicity was manageable and reversible
      although treatment discontinuation has to be considered. A prospective study
      should be encouraged to identify the optimal use of the drug.

PMID- 24722888
TI  - Athero-protective effects of High Density Lipoproteins (HDL): An ODE model of the
      early stages of atherosclerosis.
AB  - We present an ODE model which we use to investigate how High Density Lipoproteins
      (HDL) reduce the inflammatory response in atherosclerosis. HDL causes
      atherosclerotic plaque stabilisation and regression, and is an important
      potential marker and prevention target for cardiovascular disease. HDL enables
      cholesterol efflux from the arterial wall, macrophage and foam cell emigration,
      and has other athero-protective effects. Our basic inflammatory model is
      augmented to include several different ways that HDL can act in early
      atherosclerosis. In each case, the action of HDL is represented via a parameter
      in the model. The long-term model behaviour is investigated through phase plane
      analysis and simulations. Our results indicate that only HDL-enabled cholesterol
      efflux can stabilise the internalised lipid content in the lesion so that it does
      not continue to grow, but this does not reduce macrophage numbers which is
      required to stabilise the lesion or prevent rupture. HDL-enabled macrophage
      emigration guarantees lesion stabilisation by maintaining stable macrophage
      content.

PMID- 24722889
TI  - Living in a network of scaling cities and finite resources.
AB  - Many urban phenomena exhibit remarkable regularity in the form of nonlinear
      scaling behaviors, but their implications on a system of networked cities has
      never been investigated. Such knowledge is crucial for our ability to harness the
      complexity of urban processes to further sustainability science. In this paper,
      we develop a dynamical modeling framework that embeds population-resource
      dynamics-a generalized Lotka-Volterra system with modifications to incorporate
      the urban scaling behaviors-in complex networks in which cities may be linked to
      the resources of other cities and people may migrate in pursuit of higher
      welfare. We find that isolated cities (i.e., no migration) are susceptible to
      collapse if they do not have access to adequate resources. Links to other cities
      may help cities that would otherwise collapse due to insufficient resources. The
      effects of inter-city links, however, can vary due to the interplay between the
      nonlinear scaling behaviors and network structure. The long-term population level
      of a city is, in many settings, largely a function of the city's access to
      resources over which the city has little or no competition. Nonetheless, careful
      investigation of dynamics is required to gain mechanistic understanding of a
      particular city-resource network because cities and resources may collapse and
      the scaling behaviors may influence the effects of inter-city links, thereby
      distorting what topological metrics really measure. 

PMID- 24722891
TI  - Standards of practice for superficial femoral and popliteal artery angioplasty
      and stenting.
AB  - This is a Standards of Practice document endorsed by CIRSE. The authors performed
      a literature review and provide recommendations and quality improvement
      guidelines based on the most recent and highest level of evidence available to
      date on the field of Superficial Femoral and Popliteal Artery Angioplasty and
      Stenting. Standards for the use of basic and more advanced endovascular
      techniques in the femoropopliteal arteries are reported and relevant aspects of
      case selection, imaging, follow-up, and overall patient management are presented
      to guide endovascular practice in Europe. 

PMID- 24722892
TI  - Letter reply re: "endovascular treatment of a symptomatic thoracoabdominal aortic
      aneurysm by chimney and periscope techniques for total visceral and renal artery
      revascularization".

PMID- 24722893
TI  - Central stentoplasty: technique for unipedicular single midline vertebral body
      stent implantation.
AB  - Vertebral body stenting, or stentoplasty, is a novel percutaneous option in
      spinal cement augmentation. Conventional stentoplasty requires insertion of two
      paramedian stents per vertebral body through a bipedicular approach. We developed
      an unipedicular approach in which we implant a single stent into the midline of
      the vertebral body using cone-beam CT guidance and hereby describe the technical
      details and feasibility, in this technique that we termed "central stentoplasty."

PMID- 24722894
TI  - MR-guided vertebroplasty with augmented reality image overlay navigation.
AB  - PURPOSE: To evaluate the feasibility of magnetic resonance imaging (MRI)-guided
      vertebroplasty at 1.5 Tesla using augmented reality image overlay navigation.
      MATERIALS AND METHODS: Twenty-five unilateral vertebroplasties [5 of 25 (20%)
      thoracic, 20 of 25 (80%) lumbar] were prospectively planned in 5 human cadavers.
      A clinical 1.5-Teslan MRI system was used. An augmented reality image overlay
      navigation system and 3D Slicer visualization software were used for MRI display,
      planning, and needle navigation. Intermittent MRI was used to monitor placement
      of the MRI-compatible vertebroplasty needle. Cement injections (3 ml of
      polymethylmethacrylate) were performed outside the bore. The cement deposits were
      assessed on intermediate-weighted MR images. Outcome variables included type of
      vertebral body access, number of required intermittent MRI control steps,
      location of final needle tip position, cement deposit location, and
      vertebroplasty time. RESULTS: All planned procedures (25 of 25, 100%) were
      performed. Sixteen of 25 (64%) transpedicular and 9 of 25 (36%) parapedicular
      access routes were used. Six (range 3-9) MRI control steps were required for
      needle placement. No inadvertent punctures were visualized. Final needle tip
      position and cement location were adequate in all cases (25 of 25, 100%) with a
      target error of the final needle tip position of 6.1 +/- 1.9 mm (range 0.3-8.7
      mm) and a distance between the planned needle tip position and the center of the
      cement deposit of 4.3 mm (range 0.8-6.8 mm). Time requirement for one level was
      16 (range 11-21) min. CONCLUSION: MRI-guided vertebroplasty using image overlay
      navigation is feasible allowing for accurate vertebral body access and cement
      deposition in cadaveric thoracic and lumbar vertebral bodies.

PMID- 24722895
TI  - Renoduodenal fistula after transcatheter embolization of renal angiomyolipoma.
AB  - Transcatheter embolization of renal angiomyolipomas is a routinely performed,
      nephron-sparing procedure with a favorable safety profile. Complications from
      this procedure are typically minor in severity, with postembolization syndrome
      the most common minor complication. Abscess formation is a recognized but
      uncommon major complication of this procedure and is presumably due to
      superinfection of the infarcted tissue after arterial embolization. In this case
      report, we describe the formation of a renoduodenal fistula after embolization of
      an angiomyolipoma, complicated by intracranial abscess formation and requiring
      multiple percutaneous drainage procedures and eventual partial nephrectomy.

PMID- 24722896
TI  - Intranodal lymphangiogram: technical aspects and findings.
AB  - PURPOSE: To report the technical results and imaging findings of intranodal
      lymphangiogram (INL). MATERIALS AND METHODS: we studied four patients (three men,
      one woman) who had persistent chylous leakage despite conservative treatment
      after esophageal cancer surgery. Their mean age was 68 years (range 61-74 years).
      The inguinal or femoral lymph node was punctured under ultrasound guidance using
      a 60-mm-long, 23-gauge needle. If the lipiodol injected via the needle showed
      granular nodules on fluoroscopy, lipiodol injection was continued manually at a
      rate of 1 mL/3 min for INL. If the cisterna chyli was detectable on the
      lymphangiogram, it was punctured percutaneously via the abdomen by a needle under
      fluoroscopy, and thoracic duct embolization was performed. RESULTS: INL was
      successful in all patients. Lymphaticovenous anastomoses at the femoral or pelvic
      region were confirmed in all four patients. In one case, a different ipsilateral
      lymph node was punctured because major flow of lipiodol into the veins through a
      lymphaticovenous anastomosis occurred. Catheter cannulation and embolization were
      successful for three of the four patients. In unsuccessful procedures, the
      cisterna chyli was not visualized, and puncture was not possible. CONCLUSIONS:
      INL succeeded in all patients. Lipiodol leaked into the vein through a
      lymphaticovenous anastomosis at the femoral or pelvic region in all patients.

PMID- 24722897
TI  - Microvascular plug: a new embolic material for hepatic arterial skeletonization.
AB  - Arterial skeletonization before radioembolization or hepatic artery port catheter
      placement for chemotherapy is a crucial step to prevent side effects. Coils are
      commonly used as an embolic material for hepatoenteric arterial occlusion. Herein
      is reported for the first time the clinical use of a new detachable microvascular
      plug (MVP) suitable for occlusion of 1-3 mm diameter vessels. The MVP allows
      vessel embolization even in challenging anatomy such as the right gastric artery.
      Furthermore, immediate and stable vessel occlusion was observed in our pilot
      study of 16 MVP placements.

PMID- 24722898
TI  - Endovascular aneurysm repair: is imaging surveillance robust, and does it
      influence long-term mortality?
AB  - PURPOSE: Endovascular aneurysm repair (EVAR) is the dominant treatment strategy
      for abdominal aortic aneurysms. However, as a result of uncertainty regarding
      long-term durability, an ongoing imaging surveillance program is required. The
      aim of the study was to assess EVAR surveillance in Scotland and its effect on
      all-cause and aneurysm-related mortality. METHODS: A retrospective analysis of
      all EVAR procedures carried out in the four main Scottish vascular units. The
      primary outcome measure was the implementation of post-EVAR imaging surveillance
      across Scotland. Patients were identified locally and then categorized as having
      complete, incomplete, or no surveillance. Secondary outcome measures were all
      cause mortality and aneurysm-related mortality. Cause of death was obtained from
      death certificates. RESULTS: Data were available for 569 patients from the years
      2001 to 2012. All centers had data for a minimum of 5 contiguous years.
      Surveillance ranged from 1.66 to 4.55 years (median 3.03 years). Overall, 53 %
      had complete imaging surveillance, 43 % incomplete, and 4 % none. For the whole
      cohort, all-cause 5-year mortality was 33.5 % (95 % confidence interval 28.0
      38.6) and aneurysm-related mortality was 4.5 % (.8-7.3). All-cause mortality in
      patients with complete, incomplete, and no imaging was 49.9 % (39.2-58.6), 19.1 %
      (12.6-25.2), and 47.2 % (17.7-66.2), respectively. Aneurysm-related mortality was
      3.7 % (1.8-7.4), 4.4 % (2.2-8.9), and 9.5 % (2.5-33.0), respectively. All-cause
      mortality was significantly higher in patients with complete compared to
      incomplete imaging surveillance (p < 0.001). No significant differences were
      observed in aneurysm-related mortality (p = 0.2). CONCLUSION: Only half of EVAR
      patients underwent complete long-term imaging surveillance. However, incomplete
      imaging could not be linked to any increase in mortality. Further work is
      required to establish the role and deliverability of EVAR imaging surveillance.

PMID- 24722899
TI  - Transpopliteal stenting of femoral occlusions in patients with critical limb
      ischemia using a 4-French system.
AB  - PURPOSE: In many patients with critical limb ischemia (CLI), transfemoral
      endovascular recanalization is the preferred treatment. Transpopliteal treatment
      may be used in patients with inaccessible groins. This retrospective study
      regards transpopliteal stenting of superficial femoral artery (SFA) occlusions
      using a 4F system. MATERIALS AND METHODS: Eleven patients (4 male and 7 female
      [mean age 77 years]) underwent 12 attempts of transpopliteal recanalization of
      long SFA occlusions (Trans-Atlantic InterSociety Consensus B through D). All
      patients had CLI (Rutherford 4 to 6) and were nonoperable due to poor general
      condition. Indications for transpopliteal access were proximal/flush SFA
      occlusions (n = 5), failure of antegrade recanalization (n = 4), infected femoral
      femoral crossover bypass (n = 2), and occlusion of both the native SFA and the
      femoral-popliteal bypass (n = 1). The popliteal artery was punctured under
      ultrasound guidance. Occlusions were recanalized subintimally, and 4F compatible
      stents were implanted. RESULTS: Technical success rate (<30 % residual stenosis)
      was achieved in 83 % of cases. In two patients, stent dislocation occurred while
      the sheath was removed. One arteriovenous fistula was successfully treated with
      additional stenting. During 6-month follow-up, there were no major amputations,
      and three patients died from nonrelated causes. Fifty percent of patients alive
      after 6 months improved to Rutherford score <=3. The duplex restenosis (>50 %)
      rate at 6 months was 50 %. CONCLUSION: Transpopliteal primary stenting of complex
      SFA lesions in CLI for a temporary bypass is now technically feasible using a 4F
      system. Technical results are promising. Clinical results after 6 months are
      acceptable when taking into consideration that this approach may be the last
      option for limb salvage.

PMID- 24722900
TI  - Assignment of the stereochemistry and anomeric configuration of sugars within
      oligosaccharides via overlapping disaccharide ladders using MS(n).
AB  - A systematic approach is described that can pinpoint the stereo-structures (sugar
      identity, anomeric configuration, and location) of individual sugar units within
      linear oligosaccharides. Using a highly modified mass spectrometer, dissociation
      of linear oligosaccharides in the gas phase was optimized along multiple-stage
      tandem dissociation pathways (MS(n), n = 4 or 5). The instrument was a hybrid
      triple quadrupole/linear ion trap mass spectrometer capable of high-efficiency
      bidirectional ion transfer between quadrupole arrays. Different types of
      collision-induced dissociation (CID), either on-resonance ion trap or beam-type
      CID could be utilized at any given stage of dissociation, enabling either
      glycosidic bond cleavages or cross-ring cleavages to be maximized when wanted.
      The approach first involves optimizing the isolation of disaccharide units as an
      ordered set of overlapping substructures via glycosidic bond cleavages during
      early stages of MS(n), with explicit intent to minimize cross-ring cleavages.
      Subsequently, cross-ring cleavages were optimized for individual disaccharides to
      yield key diagnostic product ions (m/z 221). Finally, fingerprint patterns that
      establish stereochemistry and anomeric configuration were obtained from the
      diagnostic ions via CID. Model linear oligosaccharides were derivatized at the
      reducing end, allowing overlapping ladders of disaccharides to be isolated from
      MS(n). High confidence stereo-structural determination was achieved by matching
      MS(n) CID of the diagnostic ions to synthetic standards via a spectral matching
      algorithm. Using this MS(n) (n = 4 or 5) approach, the stereo-structures,
      anomeric configurations, and locations of three individual sugar units within two
      pentasaccharides were successfully determined. 

PMID- 24722901
TI  - A rare sinonasal entity. Sinonasal amyloidosis.

PMID- 24722902
TI  - Polypeptide backbone, C(beta) and methyl group resonance assignments of the 24
      kDa plectin repeat domain 6 from human protein plectin.
AB  - The 500 kDa protein plectin is essential for the cytoskeletal organization of
      most mammalian cells and it is up-regulated in some types of cancer. Here, we
      report nearly complete sequence-specific polypeptide backbone, (13)C(beta) and
      methyl group resonance assignments for 24 kDa human plectin(4403-4606) containing
      the C-terminal plectin repeat domain 6. 

PMID- 24722903
TI  - Use of solvent to regulate the degree of polymerisation in weakly associated
      supramolecular oligomers.
AB  - Using a tetrathiafulvalene functionalised calix[4]pyrrole (TTF-C[4]P; ) and alkyl
      diester-linked bis-dinitrophenols (), it was found that the solvent polarity and
      linker length have an effect on the molecular aggregation behaviour. 2D (1)H
      NOESY, DOSY NMR and UV-vis-NIR spectroscopic studies, as well as single crystal X
      ray diffraction analyses support these conclusions. 

PMID- 24722904
TI  - Cyclic stretch disrupts apical junctional complexes in Caco-2 cell monolayers by
      a JNK-2-, c-Src-, and MLCK-dependent mechanism.
AB  - The intestinal epithelium is subjected to various types of mechanical stress. In
      this study, we investigated the impact of cyclic stretch on tight junction and
      adherens junction integrity in Caco-2 cell monolayers. Stretch for 2 h resulted
      in a dramatic modulation of tight junction protein distribution from a linear
      organization into wavy structure. Continuation of cyclic stretch for 6 h led to
      redistribution of tight junction proteins from the intercellular junctions into
      the intracellular compartment. Disruption of tight junctions was associated with
      redistribution of adherens junction proteins, E-cadherin and beta-catenin, and
      dissociation of the actin cytoskeleton at the actomyosin belt. Stretch activates
      JNK2, c-Src, and myosin light-chain kinase (MLCK). Inhibition of JNK, Src kinase
      or MLCK activity and knockdown of JNK2 or c-Src attenuated stretch-induced
      disruption of tight junctions, adherens junctions, and actin cytoskeleton.
      Paracellular permeability measured by a novel method demonstrated that cyclic
      stretch increases paracellular permeability by a JNK, Src kinase, and MLCK
      dependent mechanism. Stretch increased tyrosine phosphorylation of occludin, ZO
      1, E-cadherin, and beta-catenin. Inhibition of JNK or Src kinase attenuated
      stretch-induced occludin phosphorylation. Immunofluorescence localization
      indicated that phospho-MLC colocalizes with the vesicle-like actin structure at
      the actomyosin belt in stretched cells. On the other hand, phospho-c-Src
      colocalizes with the actin at the apical region of cells. This study demonstrates
      that cyclic stretch disrupts tight junctions and adherens junctions by a JNK2, c
      Src, and MLCK-dependent mechanism. 

PMID- 24722906
TI  - Fermentative production of short-chain fatty acids in Escherichia coli.
AB  - Escherichia coli was engineered for the production of even- and odd-chain fatty
      acids (FAs) by fermentation. Co-production of thiolase, hydroxybutyryl-CoA
      dehydrogenase, crotonase and trans-enoyl-CoA reductase from a synthetic operon
      allowed the production of butyrate, hexanoate and octanoate. Elimination of
      native fermentation pathways by genetic deletion (DeltaldhA, DeltaadhE,
      DeltaackA, Deltapta, DeltafrdC) helped eliminate undesired by-products and
      increase product yields. Initial butyrate production rates were high (0.7 g l(-1)
      h(-1)) but quickly levelled off and further study suggested this was due to
      product toxicity and/or acidification of the growth medium. Results also showed
      that endogenous thioesterases significantly influenced product formation. In
      particular, deletion of the yciA thioesterase gene substantially increased
      hexanoate production while decreasing the production of butyrate. E. coli was
      also engineered to co-produce enzymes for even-chain FA production (described
      above) together with a coenzyme B12-dependent pathway for the production of
      propionyl-CoA, which allowed the production of odd-chain FAs (pentanoate and
      heptanoate). The B12-dependent pathway used here has the potential to allow the
      production of odd-chain FAs from a single growth substrate (glucose) in a more
      energy-efficient manner than the prior methods. 

PMID- 24722905
TI  - Intestinal alkaline phosphatase promotes gut bacterial growth by reducing the
      concentration of luminal nucleotide triphosphates.
AB  - The intestinal microbiota plays a pivotal role in maintaining human health and
      well-being. Previously, we have shown that mice deficient in the brush-border
      enzyme intestinal alkaline phosphatase (IAP) suffer from dysbiosis and that oral
      IAP supplementation normalizes the gut flora. Here we aimed to decipher the
      molecular mechanism by which IAP promotes bacterial growth. We used an isolated
      mouse intestinal loop model to directly examine the effect of exogenous IAP on
      the growth of specific intestinal bacterial species. We studied the effects of
      various IAP targets on the growth of stool aerobic and anaerobic bacteria as well
      as on a few specific gut organisms. We determined the effects of ATP and other
      nucleotides on bacterial growth. Furthermore, we examined the effects of IAP on
      reversing the inhibitory effects of nucleotides on bacterial growth. We have
      confirmed that local IAP bioactivity creates a luminal environment that promotes
      the growth of a wide range of commensal organisms. IAP promotes the growth of
      stool aerobic and anaerobic bacteria and appears to exert its growth promoting
      effects by inactivating (dephosphorylating) luminal ATP and other luminal
      nucleotide triphosphates. We observed that compared with wild-type mice, IAP
      knockout mice have more ATP in their luminal contents, and exogenous IAP can
      reverse the ATP-mediated inhibition of bacterial growth in the isolated
      intestinal loop. In conclusion, IAP appears to promote the growth of intestinal
      commensal bacteria by inhibiting the concentration of luminal nucleotide
      triphosphates.

PMID- 24722907
TI  - Towards in vivo regulon kinetics: PurR activation by 5-phosphoribosyl-alpha-1
      pyrophosphate during purine depletion in Lactococcus lactis.
AB  - Short-term adaptation to changing environments relies on regulatory elements
      translating shifting metabolite concentrations into a specifically optimized
      transcriptome. So far the focus of analyses has been divided between regulatory
      elements identified in vivo and kinetic studies of small molecules interacting
      with the regulatory elements in vitro. Here we describe how in vivo regulon
      kinetics can describe a regulon through the effects of the metabolite controlling
      it, exemplified by temporal purine exhaustion in Lactococcus lactis. We deduced a
      causal relation between the pathway precursor 5-phosphoribosyl-alpha-1
      pyrophosphate (PRPP) and individual mRNA levels, whereby unambiguous and
      homogeneous relations could be obtained for PurR regulated genes, thus linking a
      specific regulon to a specific metabolite. As PurR activates gene expression upon
      binding of PRPP, the pur mRNA curves reflect the in vivo kinetics of PurR PRPP
      binding and activation. The method singled out the xpt-pbuX operon as kinetically
      distinct, which was found to be caused by a guanine riboswitch whose regulation
      was overlaying the PurR regulation. Importantly, genes could be clustered
      according to regulatory mechanism and long-term consequences could be
      distinguished from transient changes--many of which would not be seen in a long
      term adaptation to a new environment. The strategy outlined here can be adapted
      to analyse the individual effects of members from larger metabolomes in virtually
      any organism, for elucidating regulatory networks in vivo.

PMID- 24722908
TI  - Differential regulation of the two-component regulatory system senX3-regX3 in
      Mycobacterium tuberculosis.
AB  - The highly successful pathogen Mycobacterium tuberculosis (Mtb) has evolved
      strategies to adapt to various stress conditions, thus promoting survival within
      the infected host. The two-component regulatory system (2CRS) senX3-regX3, which
      has been implicated in the Mtb response to inorganic phosphate depletion, is
      believed to behave as an auto-regulatory bicistronic operon. Unlike other 2CRS,
      Mtb senX3-regX3 features an intergenic region (IR) containing several
      mycobacterium interspersed repetitive units (MIRU) of unknown function. In this
      study, we used a lacZ reporter system to study the promoter activity of the 5'
      untranslated region of senX3, and that of various numbers of MIRUs in the senX3
      regX3 IR, during axenic Mtb growth in nutrient-rich broth, and upon exposure to
      growth-restricting conditions. Activity of the senX3 promoter was induced during
      phosphate depletion and nutrient starvation, and IR promoter activity under these
      conditions was directly proportional to the number of MIRUs present. Quantitative
      reverse transcriptase (qRT)-PCR analysis of exponentially growing Mtb revealed
      monocistronic transcription of senX3 and regX3, and, to a lesser degree,
      bicistronic transcription of the operon. In addition, we observed primarily
      monocistronic upregulation of regX3 during phosphate depletion of Mtb, which was
      confirmed by Northern analysis in wild-type Mtb and by RT-PCR in a senX3
      disrupted mutant, while upregulation of regX3 in nutrient-starved Mtb was chiefly
      bicistronic. Our findings of differential regulation of senX3-regX3 highlight the
      potential regulatory role of MIRUs in the Mtb genome and provide insight into the
      regulatory mechanisms underlying Mtb adaptation to physiologically relevant
      conditions. 

PMID- 24722909
TI  - MgtE is a dual-function protein in Pseudomonas aeruginosa.
AB  - The opportunistic pathogen Pseudomonas aeruginosa causes a wide range of
      infections, including chronic biofilm infections in the lungs of individuals with
      cystic fibrosis. We previously found that the inner-membrane protein MgtE can
      function both as a magnesium transporter and a virulence modulator, although the
      exact mechanism governing these activities is unclear. To address this issue, we
      carried out an experimental characterization of P. aeruginosa MgtE and generated
      a computer-rendered model. Our in silico analysis demonstrated the structural
      similarity of P. aeruginosa MgtE to that of the crystal structure of MgtE in
      Thermus thermophilus. Experimentally, we verified that MgtE is not essential for
      growth and found that it may not be involved directly in biofilm formation, even
      under low-magnesium conditions. We demonstrated both magnesium transport and
      cytotoxicity-regulating functions, and showed that magnesium-binding sites in the
      connecting helix region of MgtE are vital in coupling these two functions.
      Furthermore, limiting magnesium environments stimulated mgtE transcriptional
      responses. Our results suggested that MgtE might play an important role in
      linking magnesium availability to P. aeruginosa pathogenesis. 

PMID- 24722910
TI  - [Oral lichen planus. Insight into the pathogenesis and therapeutic options].
AB  - Oral lichen planus is a common, chronic mucosal disease associated with T-cell
      mediated immunological dysfunction. The disease is classified in a painful red
      form with erosions and ulcerations and a less painful to painless white form with
      reticular, papular and plaque lesions. In a small proportion of cases, the
      lesions may develop into a squamous cell carcinoma. Corticosteroids are the
      mainstay of the therapy; the combination of systemic and topical corticosteroids
      is often very effective. Topical calcineurin inhibitors, especially tacrolimus,
      have produced long-term responses in clinical studies. We describe a patient with
      excellent response to therapy with tacrolimus mouthrinse and systemic
      corticosteroids. 

PMID- 24722911
TI  - [Pyogenic granuloma of the oral mucosa].
AB  - Pyogenic granuloma is regarded as a vascular proliferation that may result from
      trauma or local irritation. The most common intraoral site is the gingiva,
      affected in 75 % of cases. Therapy of pyogenic granuloma consists of surgical
      excision. Recurrence after excision may occur. In our patient, there were no post
      operative complications. 

PMID- 24722913
TI  - Effectiveness of an educational intervention on the management of type 2 diabetic
      patients hospitalized in Internal Medicine: results from the FADOI-DIAMOND study.
AB  - Appropriate management of hyperglycemia is crucial for patients with type 2
      diabetes. Aim of the FADOI-DIAMOND study was to evaluate real-world management of
      type 2 diabetic patients hospitalized in Internal Medicine wards (IMW) and the
      effects of a standardized educational intervention for IMW staff. DIAMOND has
      been carried out in 53 Italian IMW, with two cross-sectional surveys interspersed
      with an educational program (PRE phase and POST phase). In PRE phase, each center
      reviewed the charts of the last 30 hospitalized patients with known type 2
      diabetes. An educational program was conducted in each center by means of the
      "outreach visit," a face-to-face meeting between IMW staff and a trained external
      expert. Six months after, each center repeated the data collection (POST phase),
      specular to the PRE. A total of 3,167 patients were enrolled (1,588 PRE and 1,579
      POST). From PRE phase to POST, patients with registered anthropometric data (54.1
      vs. 74.9 %, p < 0.001) and in-hospital/recent measurement of glycated hemoglobin
      (48.2 vs. 61.4 %, p < 0.005) increased significantly. After educational program,
      more patients received insulin during hospitalization (68.3 vs. 63.6 %, p =
      0.005). A more relevant variation in glycemia during hospitalization was observed
      in POST phase than PRE (-22.2 vs. -15.5 mg/dL, p < 0.001), without differences as
      for occurrence of hypoglycemia (12.3 vs. 11.9 %). A one-shot educational
      intervention led to persistent improvement in the management of hospitalized
      patients with type 2 diabetes and to significant better glycemic control. Further
      studies might evaluate the effectiveness of a more aggressive educational
      program, on both management and outcomes. 

PMID- 24722914
TI  - Adenovirus-specific IgG maturation as a surrogate marker in acute exacerbations
      of COPD.
AB  - BACKGROUND: B cells in airways and lung parenchyma may be involved in COPD
      evolution; however, whether their pathogenic role is beneficial or harmful
      remains controversial. The objective of this study was to investigate the
      maturation of adenovirus-specific immunoglobulins in patients with COPD with
      respect to clinical outcome. METHODS: The presence of adenovirus-specific
      immunoglobulins during acute exacerbation of COPD (AECOPD) was analyzed at
      exacerbation and 2 to 3 weeks later. Patients with detectable adenovirus-specific
      IgM and low IgG avidity were grouped into fast and delayed IgG maturation. The
      clinical outcome of both groups was evaluated. RESULTS: Of 208 patients, 43
      (20.7%) had serologic evidence of recent adenovirus infection and were grouped by
      fast IgG maturation (26 patients) and delayed IgG maturation (17 patients).
      Baseline characteristics, AECOPD therapy, and duration of hospitalization were
      similar in both groups, but the AECOPD recurrence rate within 6 months was higher
      (P = .003), and there was a trend for earlier AECOPD-related rehospitalizations
      (P = .061) in the delayed IgG maturation group. The time to rehospitalization or
      death within 2 years was shorter in patients with delayed IgG maturation (P =
      .003). Adenovirus-specific IgG maturation was an independent predictor of the
      number of AECOPD recurrences within 6 months (P = .001) and the occurrence of
      hospitalization or death within 2 years (P = .005). CONCLUSIONS: Delayed
      immunoglobulin avidity maturation following COPD exacerbation is associated with
      worse outcomes. TRIAL REGISTRY: ISRCTN Register; No.: ISRCTN77261143; URL:
      www.isrctn.org.

PMID- 24722912
TI  - Oleic acid modulates mRNA expression of liver X receptor (LXR) and its target
      genes ABCA1 and SREBP1c in human neutrophils.
AB  - PURPOSE: Regulation of liver X receptors (LXRs) is essential for cholesterol
      homeostasis and inflammation. The present study was conducted to determine
      whether oleic acid (OA) could regulate mRNA expression of LXRalpha and LXRalpha
      regulated genes and to assess the potential promotion of oxidative stress by OA
      in neutrophils. METHODS: Human neutrophils were treated with OA at different
      doses and LXR target gene expression, oxidative stress production, lipid efflux
      and inflammation state were analyzed. RESULTS: We describe that mRNA synthesis of
      both LXRalpha and ABCA1 (a reverse cholesterol transporter) was induced by OA in
      human neutrophils. This fatty acid enhanced the effects of LXR ligands on ABCA1
      and LXR expression, but it decreased the mRNA levels of sterol regulatory element
      binding protein 1c (a transcription factor that regulates the synthesis of
      triglycerides). Although OA elicited a slight oxidative stress in the short term
      (15-30 min) in neutrophils, it is unlikely that this is relevant for the
      modulation of transcription in our experimental conditions, which involve longer
      incubation time (i.e., 6 h). Of physiological importance is our finding that OA
      depresses intracellular lipid levels and that markers of inflammation, such as
      ERK1/2 and p38 mitogen-activated protein kinase phosphorylation, were decreased
      by OA treatment. In addition, 200 MUM OA reduced the migration of human
      neutrophils, another marker of the inflammatory state. However, OA did not affect
      lipid peroxidation induced by pro-oxidant agents. CONCLUSIONS: This work presents
      for the first time evidence that human neutrophils are highly sensitive to OA and
      provides novel data in support of a protective role of this monounsaturated acid
      against the activation of neutrophils during inflammation.

PMID- 24722915
TI  - Efficient simulations of the aqueous bio-interface of graphitic nanostructures
      with a polarisable model.
AB  - To fully harness the enormous potential offered by interfaces between graphitic
      nanostructures and biomolecules, detailed connections between adsorbed
      conformations and adsorption behaviour are needed. To elucidate these links, a
      key approach, in partnership with experimental techniques, is molecular
      simulation. For this, a force-field (FF) that can appropriately capture the
      relevant physics and chemistry of these complex bio-interfaces, while allowing
      extensive conformational sampling, and also supporting inter-operability with
      known biological FFs, is a pivotal requirement. Here, we present and apply such a
      force-field, GRAPPA, designed to work with the CHARMM FF. GRAPPA is an
      efficiently implemented polarisable force-field, informed by extensive plane-wave
      DFT calculations using the revPBE-vdW-DF functional. GRAPPA adequately recovers
      the spatial and orientational structuring of the aqueous interface of graphene
      and carbon nanotubes, compared with more sophisticated approaches. We apply
      GRAPPA to determine the free energy of adsorption for a range of amino acids,
      identifying Trp, Tyr and Arg to have the strongest binding affinity and Asp to be
      a weak binder. The GRAPPA FF can be readily incorporated into mainstream
      simulation packages, and will enable large-scale polarisable biointerfacial
      simulations at graphitic interfaces, that will aid the development of biomolecule
      mediated, solution-based graphene processing and self-assembly strategies. 

PMID- 24722916
TI  - Analysis of the cost and efficiency relationship: experience in the Turkish pay
      for performance system.
AB  - This paper analyzes the effects of the pay for performance (PFP) system on the
      efficiencies of public and private hospitals in Turkey. In order to evaluate
      these effects, we examine the relationship between hospital efficiency and health
      care costs in Turkey, and address the impact of the PFP system on the
      efficiencies of public and private hospitals. In an effort to analyze the
      efficiencies of public and private hospitals, this study uses data envelopment
      analysis. The Malmquist Productivity Index is also used to analyze the patterns
      of efficiency change for the study years from 2001 to 2008. This study shows that
      health care costs and hospital efficiency are negatively correlated for private
      hospitals, while they are positively correlated for public hospitals. In other
      words, increased health care costs might reduce efficiency in private hospitals
      in contrast to public hospitals. Our findings also indicate that average
      efficiencies of public hospitals tend to increase, particularly during the
      implementation period of PFP system. The efficiency trend of private hospitals,
      conversely, decreased in the latter periods of the PFP system. Suggestions for
      improvement are provided to the health care policy makers regarding the impact of
      health care reforms on public and private hospitals. 

PMID- 24722917
TI  - Characterization of breast cancers with PI3K mutations in an academic practice
      setting using SNaPshot profiling.
AB  - Mutations in the PIK3CA gene are common in breast cancer and represent a
      clinically useful therapeutic target. Several larger, population-based studies
      have shown a positive prognostic significance associated with these mutations.
      This study aims to further identify characteristics of patients harboring PIK3CA
      mutations while evaluating the clinical impact of genomic testing for these
      mutations. Tumors from 312 patients at Vanderbilt-Ingram Cancer Center were
      analyzed for PIK3CA mutations using a multiplex screening assay (SNaPshot).
      Mutation rates, receptor status, histopathologic characteristics, and time to
      recurrence were assessed. The number of patients participating in clinical
      trials, specifically trials relating to the PIK3CA mutation, was examined.
      Statistically significant differences between wild-type and mutated tumors were
      determined using the Wilcoxon, Pearson, and Fischer exact tests. The PIK3CA
      mutation was found in 25 % of tumors tested. Patients with PIK3CA mutations were
      significantly more likely to express hormone receptors, be of lower combined
      histological grade, and have a reduced time to recurrence. Patients found to have
      a PIK3CA mutation were significantly more likely to enter a PIK3CA-specific
      clinical trial. In addition to confirming previously established positive
      prognostic characteristics of tumors harboring PIK3CA mutations, this study
      demonstrates the feasibility and utility of mutation profiling in a clinical
      setting. PIK3CA mutation testing impacted treatment and resulted in more patients
      entering mutation-specific clinical trials. 

PMID- 24722918
TI  - Peroxisomes are juxtaposed to strategic sites on mitochondria.
AB  - Peroxisomes are ubiquitous and dynamic organelles that house many important
      pathways of cellular metabolism. In recent years it has been demonstrated that
      mitochondria are tightly connected with peroxisomes and are defective in several
      peroxisomal diseases. Indeed, these two organelles share metabolic routes as well
      as resident proteins and, at least in mammals, are connected via a vesicular
      transport pathway. However the exact extent of cross-talk between peroxisomes and
      mitochondria remains unclear. Here we used a combination of high throughput
      genetic manipulations of yeast libraries alongside high content screens to
      systematically unravel proteins that affect the transport of peroxisomal proteins
      and peroxisome biogenesis. Follow up work on the effector proteins that were
      identified revealed that peroxisomes are not randomly distributed in cells but
      are rather localized to specific mitochondrial subdomains such as mitochondria-ER
      junctions and sites of acetyl-CoA synthesis. Our approach highlights the
      intricate geography of the cell and suggests an additional layer of organization
      as a possible way to enable efficient metabolism. Our findings pave the way for
      further studying the machinery aligning mitochondria and peroxisomes, the role of
      the juxtaposition, as well as its regulation during various metabolic conditions.
      More broadly, the approaches used here can be easily applied to study any
      organelle of choice, facilitating the discovery of new aspects in cell biology.

PMID- 24722919
TI  - Fret studies of conformational changes in heparin-binding peptides.
AB  - FRET (Forster Resonance Energy Transfer) was applied to study structural
      properties of heparin-binding peptides containing the sequence XBBBXXBX where 'X'
      represents hydropathic or uncharged and 'B' represents basic amino acids.
      Internally quenched fluorogenic peptides were synthesized containing the
      fluorescent donor oaminobenzoic acid (o-Abz) and the acceptor dinitrophenyl
      ethylenediamine (Eddnp) group. Using the CONTIN computational package, distance
      distributions were recovered from time resolved fluorescence data, associated to
      end-to-end distances of the peptides. The peptides containing three or four
      repeat units have random structure in aqueous medium, and the interaction with
      low molecular weight heparin stabilized short end-to end distances. Experiments
      in water/trifluoroethanol (TFE) mixtures showed changes in distance distributions
      compatible with compact conformations stabilized above 40% volume content of TFE
      in the mixture. Similar changes in distance distributions were also observed for
      the peptides in interaction with SDS micelles in aqueous suspensions and circular
      dichroism data revealed alpha-helix formation in the peptides in interaction with
      heparin, SDS micelles or the co-solvent TFE. The process is dependent on
      electrostatic and hydrogen bond interactions and the end-to-end distances
      obtained are smaller than expected for the peptides in linear alpha-helix
      conformation, indicating the occurrence of structural arrangements leading to
      additional decrease in the distances.

PMID- 24722920
TI  - Stabilization of NADH-dehydrogenase in mitochondria by guanosine phosphates and
      adenosine phosphates.
AB  - It is known that one of the reasons, leading to the development of neuromuscular
      diseases, including Parkinson's disease, is damage of the mitochondrial NADH
      dehydrogenase. Perhaps, it happens when NADH-dehydrogenase loses connection with
      its coenzyme--flavine mononucleotide (FMN) that occurs at various influences on
      the enzyme. Previously, we have developed a method, based on fluorescence
      spectroscopy, to monitor the rate of exit of FMN from isolated mitochondria to
      solution. Also, we obtained the data that this process is blocked by the enzyme
      substrate - NADH or by the product - NAD. Recently, we found that this process is
      strongly blocked by adenine analogs of NAD, contained phosphates: ATP, ADP, and
      AMP. Adenosine phosphates are able to stabilize the FMN molecule in NADH
      dehydrogenase. Using fluorescence spectroscopy and photocolorimetry, we have
      tested also other natural purine compounds - cAMP, cGMP, GMP, GDP, GTP, IMP,
      inosine, guanine, and caffeine. It is found that such derivatives of guanine as
      GMP, GDP, and GTP can prevent the release of FMN into solution. Guanine, cGMP,
      cAMP and caffeine did not prevent this process. The obtained data allow
      understand the mechanism of mitochondrial diseases, involving damage of
      mitochondrial NADH-dehydrogenase, and may help in development of medicines for
      treatment of these diseases.

PMID- 24722921
TI  - The relation of childhood physical activity and aerobic fitness to brain function
      and cognition: a review.
AB  - Physical inactivity has been shown to increase the risk for several chronic
      diseases across the lifespan. However, the impact of physical activity and
      aerobic fitness on childhood cognitive and brain health has only recently gained
      attention. The purposes of this article are to: 1) highlight the recent emphasis
      for increasing physical activity and aerobic fitness in children's lives for
      cognitive and brain health; 2) present aspects of brain development and cognitive
      function that are susceptible to physical activity intervention; 3) review
      neuroimaging studies examining the cross-sectional and experimental relationships
      between aerobic fitness and executive control function; and 4) make
      recommendations for future research. Given that the human brain is not fully
      developed until the third decade of life, preadolescence is characterized by
      changes in brain structure and function underlying aspects of cognition including
      executive control and relational memory. Achieving adequate physical activity and
      maintaining aerobic fitness in childhood may be a critical guideline to follow
      for physical as well as cognitive and brain health. 

PMID- 24722922
TI  - Can we make a placenta in the Petri dish?

PMID- 24722923
TI  - Parallel deposition of size-selected clusters: a novel technique for studying
      size-selectivity on the atomic scale.
AB  - A new size-selected cluster deposition technique referred to as "parallel
      deposition" is presented. An ion beam of multi-sized Aun clusters was spatially
      separated into individual cluster sizes by utilizing a Wien filter and the
      clusters spatially separated based on their atomic sizes were simultaneously
      deposited on a SiO2/Si(100) substrate. Parallel-deposited Aun clusters (n = 6, 7,
      and 8) on the SiO2/Si(100) substrate showed even-odd oxidation behaviour upon
      exposure to an atomic oxygen atmosphere, demonstrating the potential of this new
      technique to study the size-dependent properties of deposited clusters in various
      research fields. 

PMID- 24722924
TI  - Defocused differential interference contrast microscopy imaging of single
      plasmonic anisotropic nanoparticles.
AB  - We present the defocused differential interference contrast (DIC) imaging of gold
      nanorods. We found that the scattered light and the defocus aberration play an
      important role in the formation of orientation-dependent DIC image patterns of a
      gold nanorod. Interestingly, the scattered light from a gold nanorod aligned
      closer to the polarization directions enables us to directly resolve its spatial
      orientation under a defocused DIC microscope. 

PMID- 24722925
TI  - External Nasal Lesion in a Middle-aged Man.

PMID- 24722926
TI  - Tokenism in psychology: standing on the shoulders of small boys.
AB  - Tokenism is a situation in which a member of a distinctive category is treated
      differently from other people. This article is about the situation in which
      Tokens (people perceived as distinctive) are considered experts on something for
      having the properties of a token (the thing which makes them distinctive). Tokens
      who differ by appearance or by being born into another culture might be
      considered experts on cultures grouped into the same racial/cultural category.
      Tokens who differ by being skilled in number-related mathematics might be
      considered experts on the mathematization of phenomena. Tokens might say that
      some result is valid for all people in some racial/cultural category without
      sufficient evidence, or use number-related mathematics as a mathematization of
      psychological phenomena without trying to find more abstract mathematizations.
      This harms psychological research. A possible future genesis of cultural and
      number tokenisms is discussed, and some suggestions to improve the discourse
      offered. The effect of tokenism might be diminished if psychologists focus on
      more proper thinking about psychological phenomena. 

PMID- 24722927
TI  - Quantitative and real-time effects of carbon quantum dots on single living HeLa
      cell membrane permeability.
AB  - The interaction between carbon quantum dots (CQDs) and a single living cell was
      explored in real time. Here, we provide the quantitative data on the permeability
      of the HeLa cell membrane in the presence of CQDs with different surface
      functional groups (CQDs terminated with -OH/-COOH (CQD-OH), -PEG (CQD-PEG), and 
      NH2 (CQD-NH2)). Although these CQDs have very low toxicity towards HeLa cells,
      they still increase the cell membrane permeability by 8%, 13%, and 19% for CQD
      PEG, CQD-OH, and CQD-NH2, respectively, and this kind of permeability was
      irreversible. These observations are valuable for promoting the bio-applications
      of carbon nanostructures in living systems. 

PMID- 24722928
TI  - Analysis of Pseudomonas aeruginosa PAO1 lipid A changes during the interaction
      with model organism, Caenorhabditis elegans.
AB  - Lipopolysaccharide (LPS) is the main surface constituent of Gram-negative
      bacteria. Lipid A, the hydrophobic moiety, outer monolayer of the outer cell
      membrane forms the major component of LPS. Immunogenic Lipid A is recognized by
      the innate immune system through the TLR 4/MD-2 complex. Pseudomonas aeruginosa
      PAO1, a Gram-negative bacterium is known to cause nosocomial infection and known
      for its adaptation to adverse environmental conditions. Pseudomonas aeruginosa
      can infect a broad host spectrum including Caenorhabditis elegans, a simple free
      living soil nematode. Here, we reveal that PAO1 modifies its Lipid A during the
      host interaction with C. elegans. The penta-acylated form of Lipid A was
      identified by using matrix assisted laser desorption ionization-time of flight
      analysis and the beta-(1,6)-linked disaccharide of glucosamine with phosphate
      groups, 2 and 2' amide linked fatty acid chain and 3 and 3' ester linked fatty
      acids were investigated for the modification using the non destructive (1)H NMR,
      spin-lattice (T1) relaxation measurement, differential scanning calorimetry. T1
      relaxation measurements showed that the 2 and 2' amide linked fatty acid chain, 
      CH in the glucosamine disaccharide of PAO1 lipid A, in an exposed host had a
      different spin lattice relaxation time compared to an unexposed host and the
      findings were reconfirmed using in vitro human corneal epithelial cells cell
      lines. Furthermore, scanning electron microscope and confocal laser scanning
      microscopy analysis revealed that the P. aeruginosa PAO1 biofilm formation was
      disturbed in the exposed host condition. The daf-12, daf-16, tol-1, pmk-1, ins-7
      and ilys3 immune genes of C. elegans were examined with live bacterial and
      isolated lipid moiety infection and the expression was found to be highly
      specific. Overall, the present study revealed that PAO1 modified its 2 and 2'
      amide linked fatty acid chain in the lipid A of PAO1 LPS during the exposed host
      condition.

PMID- 24722929
TI  - [Patterns of weight development before the diagnosis of type 2 diabetes--Moderate
      overweight should not increase--in total, overweight should be reduced].

PMID- 24722930
TI  - [Cardiology: innovative medicine from molecular diagnosis to modern
      interventional technology].

PMID- 24722931
TI  - [Diabetes increases short- and long-term mortality after transcatheter aortic
      valve implantation (TAVI)].
AB  - BACKGROUND AND AIM: Long-term mortality after transcatheter aortic valve
      implantation (TAVI) in elderly patients with abundant comorbidities is
      considerable. We aimed to determine the impact of diabetes on short- and long
      term mortality after TAVI. METHODS: Our study includes 300 consecutive patients
      (mean age, 82 +/- 5 years) who underwent TAVI (158 transapical, 142 transfemoral
      procedures). All patients were followed by regular telephone contacts. 36%
      suffered from diabetes. RESULTS: Diabetes could be identified as significant
      predictor of short- and long-term mortality after TAVI. In diabetic patients, 30
      day-mortality was 2,5 fold elevated (18.3% vs. 7.3%, p = 0.004). Furthermore,
      they were at significantly higher risk of peri-interventional stroke (p = 0.04),
      stage 3 acute kidney injury (p = 0.003), and prolonged ventilation (p = 0.01).
      Even after successful TAVI and discharge from hospital, long-term mortality was
      significantly elevated in diabetic patients (56% vs. 30%, p < 0.0001). Of note,
      25% of diabetic vs. only 8% of non-diabetic patients died from cardiac causes
      during follow-up, suggesting that TAVI is not able to reduce cardiac-related
      mortality risk in diabetic patients to the same extent as in non-diabetics.
      CONCLUSION: Diabetes represents a powerful predictor of adverse early and late
      outcome after TAVI. These findings should be incorporated into the assessment of
      the risk-to-benefit ratio of TAVI in diabetic patients.

PMID- 24722932
TI  - [Will telemonitoring be adopted by patients with chronic heart failure?].
AB  - BACKGROUND: Remote Patient Management for chronic heart failure (CHF) is gaining
      increasing importance in health care. Telemonitoring is defined as daily
      measuring of health parameters by the patient and their transmission to a
      telemedical centre. The adherence of this action by the patient can be considered
      as a measure for RPM adoption. METHODS: The randomized controlled clinical trial
      TIM-HF (NCT 00543881) was conducted between 2008 and 2010 with 710 CHF patients
      with the primary endpoint total mortality for a mean follow-up of 21.5 +/- 7.2
      months. The non-prespecified analysis of adherence to daily measuring of ECG,
      blood pressure, weight and self-assessment was focused on sociodemographic and
      disease-related factors of the 354 RPM patients. RESULTS: The mean adherence to
      telemonitoring was more than 80% (absolute adherence: 81.8 +/- 22.8%, relative
      adherence: 88.9 +/- 21.5%). From the beginning of treatment 6.5% of the patients
      (23/354) have shown an adherence below average. The high adherence of the
      majority of the patients was stable for the entire study duration and
      irrespective of age, sex, severity of the disease and the presence of mild to
      moderate depression. CONCLUSION: A high adherence can be achieved by individual
      training of the patient regarding the handling of his disease, the use of
      telemedical devices and an easy-to-use telemonitoring system. The majority of the
      informed self-determined CHF patients NYHA class II/III are adopting
      telemonitoring and are adherent in the long term.

PMID- 24722933
TI  - [Aortitis due to Salmonella].
AB  - HISTORY AND CLINICAL FINDINGS: A 72-year-old man received treatment with
      amoxicillin/clavulanic acid because of fever and abdominal pain as an outpatient
      setting. Salmonella enteritidis infection was confirmed by a positive blood
      culture. The febrile patient showed abdominal tenderness on palpation.
      INVESTIGATIONS: CT and PET scans revealed an aneurysmatic soft tissue
      inflammation which was interpreted as infectious aortitis in the context of
      salmonella bacteraemia. TREATMENT AND COURSE: After several weeks of antibiotic
      treatment with ceftriaxone, an elective reconstruction using xenopericard with
      replacement of the mesenterial vessels was performed. After a postoperative
      course of antibiotics the patient recovered completely. CONCLUSION: In patients
      with positive blood cultures for Salmonella in combination with fever, back or
      abdominal pain a workup for infectious aortitis and a rapid treatment is
      recommended.

PMID- 24722934
TI  - [67-year-old woman with exercise-induced angina pectoris].

PMID- 24722935
TI  - [Iron deficiency in chronic heart failure: from diagnosis to therapy].
AB  - Anaemia and iron deficiency are frequent co-morbidities in patients with chronic
      heart failure. Both are bound to worsen an already reduced exercise capacity in
      these patients. Recent data have demonstrated that iron deficiency alone, i.e.
      without concomitant anaemia, reduces quality of life, exercise capacity and
      likely also survival. Two clinical entities should be differentiated in this
      context: absolute and functional iron deficiency, the first being an absolute
      deficiency of iron, the second representing a disturbed mobilisation capacity.
      The FAIR-HF study has shown that intravenous iron administration can improve
      quality of life and exercise capacity in affected patients. A correct diagnosis
      can easily be arrived at using parameters such as serum ferritin and transferrin
      saturation. Replenishing iron stores is most useful using the intravenous route,
      and administered doses need to be adjusted to individual needs.

PMID- 24722936
TI  - [Exercise training in heart failure patients].
AB  - Physical exercise has been recognized as a standard therapy in the guidelines for
      secondary prevention of chronic heart failure. This is mostly due to the
      overwhelming scientific evidence, including meta-analyses that have illustrated
      the positive effect of physical exercise on quality of life, hospitalisation and
      exercise capacity. However, it is crucial that patients undergo thorough clinical
      screening, including exercise testing, before starting an exercise regimen. Once
      a patient is eligible to exercise, it is also important that only approved
      exercise regimens are prescribed and that the exercise itself is monitored
      appropriately. Both, traditional moderate continuous endurance training and
      recently developed interval training have been shown to be safe and effective in
      chronic heart failure. Ideally, moderate intensity training should be started and
      later combined with interval training that is added by moderate resistance
      training in order to improve quality of life and prognosis. 

PMID- 24722937
TI  - [Is atrial fibrillation in heart failure relevant in prognosis? Pro rate
      control].

PMID- 24722938
TI  - [Is atrial fibrillation in heart failure relevant in prognosis? Pro rhythm
      control].

PMID- 24722939
TI  - Calculation of individual expected pleural drainage from total body lymph flow: a
      guide for fast-tracking removal of chest drains.

PMID- 24722940
TI  - Permanent pacemaker requirement after concomitant surgical ablation for atrial
      fibrillation.

PMID- 24722941
TI  - Reply to Tannous et al.

PMID- 24722942
TI  - Neuropilin 1 expression in human aortas, coronaries and the main bypass grafts.
AB  - OBJECTIVES: Development of intimal hyperplasia (IH) is the main pathology
      underlying graft failure following coronary artery bypass graft surgeries for
      ischaemic heart diseases, especially for great saphenous vein grafts which have a
      lower patency rate than internal mammary arteries. Neuropilin 1 (NRP1), which is
      a co-receptor for vascular endothelial growth factor found in vascular
      endothelial and smooth muscle cells, affects the development of IH. We examined
      the difference in NRP1 expression and distribution in human coronaries, aortas,
      mammary arteries and saphenous veins to detect a possible relation to their
      susceptibility to IH. METHODS: Ninety-five human vascular segments obtained from
      40 patients were used for the comparison of NRP1 expression between different
      groups of blood vessels by western blot and real-time PCR. Additionally, staining
      scores were generated by computerized analysis of the microscopic images obtained
      after immunofluorescence and immunohistochemical staining to compare NRP1
      expression patterns in endothelium, smooth muscles and adventitia in each vessel
      type. RESULTS: NRP1 expression in the aorta (2.03 +/- 1.44) was more than twice
      as high as mammary artery expression (0.85 +/- 0.75; n = 16, P = 0.0004); NRP1 of
      the latter (0.99 +/- 0.91) was more than 30% greater than that of the
      corresponding saphenous vein (0.73 +/- 0.69; n = 20, P = 0.0085). In adventitia,
      NRP1 receptor staining of the saphenous vein was higher (22.96 +/- 8.73) than in
      the mammary artery (15.83 +/- 7.13; n = 7, P = 0.049). Variations in NRP1 protein
      levels were accompanied by parallel variations in its mRNA levels (n = 15, P =
      0.34). CONCLUSIONS: Autologous saphenous vein grafts, unlike internal mammary
      artery grafts, have lower NRP1 expression and abundant adventitial distribution
      of NRP1 within their walls; this may correlate with higher susceptibility to IH
      development.

PMID- 24722943
TI  - New indicator of postoperative delayed awakening after total aortic arch
      replacement.
AB  - OBJECTIVE: Impact of the decrease of regional cerebral oxygen saturation (rSO2)
      on postoperative delayed awakening after total aortic arch replacement (TAR) was
      validated. METHODS: From 2008 to 2013, 143 consecutive patients underwent TAR
      using selective antegrade cerebral perfusion. rSO2 was monitored using near
      infrared spectroscopy. We calculated a percent decrease of rSO2 (%-D) immediately
      after rewarming according to the following formula: %-D=rSO2 (X1)-rSO2 (X2)/rSO2
      (X1)*100 (%), where rSO2 (X1) was measured at the beginning of rewarming, and
      rSO2 (X2) was measured 10 min later. Delayed awakening was defined as patients
      not waking up for more than 6 h after the termination of anaesthesia. RESULTS:
      The average time to wake up was 3.6+/-2.0 h. Fourteen patients showed delayed
      awakening. %-D showed a positive linear relationship to awakening time (y=0.67x
      0.7, r=0.23, P=0.007) and receiver operating characteristic analysis showed %-D
      had a good predictive value for delayed awakening (area under the curve=0.84). %
      D was significantly different between the delayed awakening and the normal group
      (7.1+/-5.1 vs 1.3+/-6.6%, P=0.002). Two patients (1.4%) who had multicomorbidity
      with higher %-D died in the hospital due to colon necrosis and sepsis. There were
      significant differences between patients with normal and delayed awakening in
      hospital mortality (P=0.04) and transient neurological deficit (TND, P=0.007).
      CONCLUSION: The maintenance of rSO2 at the early phase of rewarming may be
      important to avoid delayed awakening or TND after TAR.

PMID- 24722944
TI  - Reply to McGuire and Gilbert.

PMID- 24722945
TI  - "Awake-awake" or "conscious sedation" for awake craniotomies?

PMID- 24722946
TI  - Visual field findings after a ruptured intracranial aneurysm.
AB  - BACKGROUND: Visual field defects (VFDs) negatively affect activities of daily
      living and rehabilitation following aneurysmal subarachnoid haemorrhage (aSAH).
      The aim here was to assess VFDs in patients with aSAH and their associations with
      age, gender, aSAH severity, and clinical outcome. METHODS: Patients admitted to
      Helsinki University Central Hospital and treated during 2011 were participants in
      this prospective study. Findings obtained with the Octopus 900 perimeter (Haag
      Streit Inc, Koenic, Switzerland), the Goldmann perimeter (Haag-Streit Inc, Bern,
      Switzerland), or the confrontation visual field test on admission and 3 days, 14
      days, 2 to 4 months, and 6 months postoperatively were assigned to 16 classes.
      Associations between post-chiasmal VFDs and relevant clinical, radiological, and
      demographic data were analysed with uni- and multivariate logistic regression.
      RESULTS: Of 105 survivors at 6 months, 20 (19 %) had VFDs occurring for aneurysm-
      or operation-related reasons; homonymous hemianopias or quadrantanopias were the
      most common finding, occurring in 16 patients (15 %). Posterior ischaemic optic
      neuropathy presented in two patients (2 %). Ten survivors (10 %) no longer
      fulfilled visual field requirements for driving licences. Significant
      associations emerged between VFDs at 6 months and the Hunt and Hess (H&H), World
      Federation of Neurosurgical Societies (WFNS), and Fisher grades on admission,
      presence of intracerebral haemorrhage (ICH), hydrocephalus, or postoperative
      infarction, and higher modified Rankin Scale scores at 6 months. Multivariate
      logistic regression showed the H&H grade and presence of ICH to independently
      predict VFDs. CONCLUSIONS: Assessing VFDs is advisable, especially among patients
      with poor-grade aSAH (H&H grade IV or V) and ICH.

PMID- 24722947
TI  - CXC chemokine ligand 12 (CXCL12) and its receptor CXCR4.
AB  - Chemokines were recognized originally for their ability to dictate the migration
      and activation of leukocytes. However, CXC chemokine ligand 12 (CXCL12, also
      known as stromal cell-derived factor-1) and its receptor CXCR4 are the first
      chemokine and receptor that have been shown to be critical for developmental
      processes, including homing and maintenance of hematopoietic stem cells (HSCs),
      production of immune cells, homing of primordial germ cells (PGCs),
      cardiogenesis, arterial vessel branching in some organs, and appropriate
      assemblies of particular types of neurons. This review focuses on the
      pathophysiological relevance of CXCL12-CXCR4 signaling in mammals. 

PMID- 24722948
TI  - Cannabinoid receptor 1 disturbance of PPARgamma2 augments hyperglycemia induction
      of mesangial inflammation and fibrosis in renal glomeruli.
AB  - Intensive fibrosis in the glomerular microenvironment is a prominent feature of
      diabetic nephropathy. Cannabinoid receptor 1 (CB1R) reportedly mediates diabetes
      induced renal injury. However, studies on the molecular events underlying CB1R
      promotion of renal dysfunction are limited. This study is undertaken to
      investigate whether CB1R signaling via Ras or PPARgamma pathway regulates
      mesangial fibrosis in diabetic kidneys. In streptozotocin-induced diabetic rats,
      hyperglycemia induced glomerular hypertrophy and fibrosis in association with
      increased IL-1beta, fibronectin, and CB1R expressions and reduced PPARgamma2
      signaling. CB1R transgenic mice gained kidney weight, and renal glomeruli
      strongly displayed IL-1beta and fibrotic matrices. Disruption of CB1R by
      antisense oligonucleotides or inverse agonist AM251 restored PPARgamma2 signaling
      and reduced the promotional effects of hyperglycemia on the expression of
      fibrogenic transcription factor c-Jun, inflammation regulator SOCS3,
      proinflammatory cytokines, and accumulation of fibrotic matrix. PPARgamma agonist
      rosiglitazone reduced the hyperglycemia-mediated enhancement of CB1R signaling,
      inflammation, and glomerular fibrosis in diabetic animals. In vitro, CB1R
      antagonism restored PPARgamma2 action and reduced the promotional effects of high
      glucose on Ras, ERK, c-Jun, SOCS3 signaling, IL-1beta, and fibronectin expression
      in renal mesangial cells. Activation of PPARgamma2 reduced the high glucose
      induced CB1R expression in mesangial cells. Taken together, CB1R signaling
      contributes to the hyperglycemia disturbance of PPARgamma2 signaling and
      increases inflammatory cytokine secretion and fibrotic matrix deposition in renal
      glomeruli. CB1R mediates the hyperglycemia-induced inflammation and fibrosis in
      mesangial cells by regulating Ras, ERK, and PPARgamma2 signaling. CB1R blockade
      has a therapeutic potential to reduce the deleterious actions of hyperglycemia on
      renal glomerular integrity. KEY MESSAGE: Hyperglycemia increases glomerular
      fibrosis, inflammation, and CB1R signaling. CB1R signaling promotes fibrosis and
      inflammation of renal tissue. Loss of CB1R function alleviates diabetes-mediated
      renal deterioration. PPARgamma agonist decreases CB1R expression in diabetic
      renal glomeruli. Ras and ERK mediated CB1R promotion of fibrosis matrix
      deposition in mesangial cells.

PMID- 24722949
TI  - Detection of fibroproliferation by chest high-resolution CT scan in resolving
      ARDS.
AB  - BACKGROUND: In ARDS, the extent of fibroproliferative activity on chest high
      resolution CT (HRCT) scan has been reported to correlate with poorer short-term
      outcomes and pulmonary-associated quality of life. However, clinical factors
      associated with HRCT scan fibroproliferation are incompletely characterized. We
      questioned if lung compliance assessed at the bedside would be associated with
      fibroproliferation on HRCT scans obtained during the resolution phase of ARDS.
      METHODS: We used data from a published randomized, controlled clinical trial in
      ARDS. All patients were cared for using a low tidal volume strategy. Demographic
      data and ventilator parameters were examined in association with radiologic
      scores from chest HRCT scans obtained 14 days after diagnosis. RESULTS: Data from
      82 patients with ARDS were analyzed. Average static respiratory compliance over
      the first 14 days after diagnosis was inversely associated with chest HRCT scan
      reticulation (rho = -0.46); this relationship persisted in multivariable analysis
      including APACHE (Acute Physiology and Chronic Health Evaluation) II scores,
      initial Pao2/Fio2, pneumonia diagnosis, and ventilator days. Average static
      respiratory compliance was also lower among patients with bronchiectasis at day
      14 (P = .007). Initial static respiratory compliance obtained within the first
      day after ARDS diagnosis was correlated inversely with the presence of HRCT scan
      reticulation (rho = -0.38) and was lower among patients who demonstrated
      bronchiectasis on the day 14 HRCT scan (P = .008). CONCLUSIONS: In patients with
      ARDS, diminished lung compliance measured bedside was associated with radiologic
      fibroproliferation 14 days post diagnosis. Establishing factors that predispose
      to development of excessive fibroproliferation with subsequent confirmation by
      chest HRCT scan represents a promising strategy to identify patients with ARDS at
      risk for poorer clinical outcomes.

PMID- 24722950
TI  - Demographic Risk Factors and Gambling Preference May Not Explain the High
      Prevalence of Gambling Problems Among the Population with Migration Background:
      Results from a German Nationwide Survey.
AB  - There are high proportions of problem gamblers among individuals who themselves
      or whose parents immigrated to Germany. This study aimed to examine whether
      demographic risk factors and gambling preference may explain the higher
      prevalence of gambling problems among those with migration background (MB). Data
      was obtained from a nationwide telephone survey which was part of the project
      "Pathological Gambling and Epidemiology" (PAGE). The sample comprised 15,023
      study participants aged 14-64 years living in Germany. Participants who had
      reported gambling within their lifetime (n = 6,406) were defined as gamblers and
      categorized according to their MB (n = 1,209 with MB), additional demographic
      characteristics (sex, age, marital status, household size, education,
      occupation), preferred types of gambling (21 categories covering the gambling
      types available in Germany), and the count of lifetime gambling problem symptoms
      (0-10 criteria of the fourth Diagnostic and Statistical Manual of Mental
      Disorders). Estimates from a negative binomial regression revealed that there is
      a 146.2% increase in the expected count of gambling problem symptoms for gamblers
      with MB compared to those without MB. The percentage decreased to 102.5 and 97.6%
      after adjustment for demographic characteristics and further adjustment for
      preferred types of gambling, respectively. Demographic risk factors and gambling
      preference may partially mediate but not completely explain the higher prevalence
      of gambling problems among the population with MB. Having an MB may be considered
      as an independent risk factor for gambling problems, which indicates a need for
      culturally sensitive prevention and treatment measures.

PMID- 24722951
TI  - Thrombotic risk stratification using computational modeling in patients with
      coronary artery aneurysms following Kawasaki disease.
AB  - Kawasaki disease (KD) is the leading cause of acquired heart disease in children
      and can result in life-threatening coronary artery aneurysms in up to 25 % of
      patients. These aneurysms put patients at risk of thrombus formation, myocardial
      infarction, and sudden death. Clinicians must therefore decide which patients
      should be treated with anticoagulant medication, and/or surgical or percutaneous
      intervention. Current recommendations regarding initiation of anticoagulant
      therapy are based on anatomy alone with historical data suggesting that patients
      with aneurysms [Formula: see text]8 mm are at greatest risk of thrombosis. Given
      the multitude of variables that influence thrombus formation, we postulated that
      hemodynamic data derived from patient-specific simulations would more accurately
      predict risk of thrombosis than maximum diameter alone. Patient-specific blood
      flow simulations were performed on five KD patients with aneurysms and one KD
      patient with normal coronary arteries. Key hemodynamic and geometric parameters,
      including wall shear stress, particle residence time, and shape indices, were
      extracted from the models and simulations and compared with clinical outcomes.
      Preliminary fluid structure interaction simulations with radial expansion were
      performed, revealing modest differences in wall shear stress compared to the
      rigid wall case. Simulations provide compelling evidence that hemodynamic
      parameters may be a more accurate predictor of thrombotic risk than aneurysm
      diameter alone and motivate the need for follow-up studies with a larger cohort.
      These results suggest that a clinical index incorporating hemodynamic information
      be used in the future to select patients for anticoagulant therapy. 

PMID- 24722952
TI  - Hodgkin lymphoma incidence in California Hispanics: influence of nativity and
      tumor Epstein-Barr virus.
AB  - PURPOSE: For classical Hodgkin lymphoma (HL), migrant studies could elucidate
      contributions of environmental factors (including Epstein-Barr virus (EBV)) to
      the lower rates in non-whites. Given the well-described etiologic complexity of
      HL, this research requires a large, immigrant population, such as California
      Hispanics. METHODS: With 1988-2004 California Cancer Registry data (2,595
      Hispanic, 8,637 white HL cases) and tumor cell EBV status on a subset (218
      Hispanics, 656 whites), we calculated ethnicity- and nativity-specific HL
      incidence rates simultaneously by age, sex, and histologic subtype, and tumor
      cell EBV prevalence. RESULTS: Compared with white rates, Hispanic HL rates were
      lower overall (70 %) and for nodular sclerosis HL, particularly among young
      adults (60-65 % for females). However, they were higher among children (200 %)
      and older adults, and for mixed cellularity HL. Compared with rates in foreign
      born Hispanics, rates in US-born Hispanics were higher among young adults
      (>threefold in females), lower for children and adults over age 70, and
      consistently intermediate compared with rates in whites. EBV tumor prevalence was
      67, 32, and 23 % among foreign-born Hispanics, US-born Hispanics, and whites,
      respectively, although with variation by age, sex, and histology. CONCLUSIONS:
      Findings strongly implicate environmental influences, such as nativity-related
      sociodemographic differences, on HL occurrence. In addition, lower young adult
      rates and higher EBV prevalence in US-born Hispanics than in whites raise
      questions about the duration/extent of environmental change for affecting HL
      rates and also point to ethnic differences in genetic susceptibility. Lesser
      variation in mixed cellularity HL rates and greater variation in rates for
      females across groups suggest less modifiable factors interacting with
      environmental influences.

PMID- 24722953
TI  - Dairy food and nutrient intake in different life periods in relation to risk of
      ovarian cancer.
AB  - PURPOSE: High lactose intake has been suggested to increase epithelial ovarian
      cancer (EOC) risk. We evaluated the association between lactose consumed during
      specific life periods (high school, premenopause, and postmenopause) and later
      risk of EOC. METHODS: We assessed the association of dairy food and nutrient
      intake with risk of EOC during 28 years of follow-up including 764 cases in the
      Nurses' Health Study (NHS) and NHSII. Cox proportional hazards regression was
      used to model the hazard ratios (HRs) and 95% confidence intervals (CIs) for EOC
      across categories of dairy food or nutrient intake. We examined dietary intake in
      adulthood overall, as well as during premenopausal/postmenopausal years and high
      school. RESULTS: In analyses of the highest versus lowest cumulative average
      intake in adulthood, we observed a non-significant inverse association with skim
      milk intake (HR 0.76, 95% CI 0.54-1.06, p(trend) = 0.05), a non-significant
      inverse association with lactose intake (HR 0.87, 95% CI 0.69-1.11, p(trend) =
      0.22) and no association with consumption of whole milk, dairy calcium, or dairy
      fat. Similar risk estimates were observed for dairy food/nutrient intake during
      high school, premenopause or postmenopause. Lactose intake in adulthood was
      inversely associated with risk of endometrioid EOC (HR 0.32, 95% CI 0.16-0.65,
      p(trend) < 0.001). CONCLUSIONS: These findings do not support the hypothesis that
      higher lactose intake increases EOC risk. The inverse association with
      endometrioid tumors deserves further study.

PMID- 24722954
TI  - Zinc'ing sensibly: controlling zinc homeostasis at the transcriptional level.
AB  - Zinc-responsive transcription factors are found in all kingdoms of life and
      include the transcriptional activators ZntR, SczA, Zap1, bZip19, bZip23, and MTF
      1, and transcriptional repressors Zur, AdcR, Loz1, and SmtB. These factors have
      two defining features; their activity is regulated by zinc and they all play a
      central role in zinc homeostasis by controlling the expression of genes that
      directly affect zinc levels or its availability. This review summarizes what is
      known about the mechanisms by which each of these factors sense changes in
      intracellular zinc levels and how they control zinc homeostasis through target
      gene regulation. Other factors that influence zinc ion sensing are also
      discussed. 

PMID- 24722955
TI  - Hide and seek: the theory of mind of visual concealment and search.
AB  - Researchers have investigated visual search behavior for almost a century. During
      that time, few studies have examined the cognitive processes involved in hiding
      items rather than finding them. To investigate this, we developed a paradigm that
      allowed participants to indicate where they would hide (or find) an item that was
      to be found (or hidden) by a friend or a foe. We found that (i) for friends more
      than foes, participants selected the pop-out item in the display, and (ii) when
      the display was homogeneous, they selected nearby and corner items. These
      behaviors held for both hiding and finding, although hide and find behaviors were
      not identical. For pop-out displays, decision times were unusually long when
      hiding an item from a foe. These data converge on the conclusion that the
      principles of search and concealment are similar, but not the same. They also
      suggest that this paradigm will provide researchers a powerful method for
      investigating theory of mind in adults. 

PMID- 24722956
TI  - Theoretical investigation and design of high-efficiency dithiafulvenyl-based
      sensitizers for dye-sensitized solar cells: the impacts of elongating pi-spacers
      and rigidifying dithiophene.
AB  - DSSCs have been extensively investigated in the past decade, and the search for
      more efficient dyes for DSSCs remains challenging. In this work we discuss the
      influences of elongating pi-spacers and rigidifying dithiophene on the
      performance of dithiafulvenyl (DTF)-based organic dyes using density functional
      theory (DFT) and time-dependent DFT methods. We show that systematically
      elongating the pi-spacer of the DTF-2P dye by increasing the number of thiophene
      groups tends to red-shift the absorption peak and broaden the absorption range,
      thus improving the light-harvesting efficiency of DTF-2P-T and DTF-2P-2T.
      Furthermore, among the three dyes, DTF-2P-T would have the best performance
      because it performs nicely on the key parameters including the electron injection
      driving force (D), the light-harvesting efficiency (LHE), and the shift of the
      TiO2 conduction band (DeltaEcb). In particular, DTF-2P-2T has a larger LHE
      despite the smaller D and DeltaEcb compared with DTF-2P-T. Having realized the
      great merits of modification on pi-spacers, afterwards, we designed a novel dye
      by rigidifying the dithiophene moiety of DTF-2P-2T. The resulting dye is proven
      to be very promising to challenge the conversion efficiency 8.29% of DTF-2P-T due
      to the improved DeltaEcb and LHE. Our theoretical studies are expected to provide
      valuable insights into the molecular design of novel DTF-based dyes for the
      optimization of DSSC. 

PMID- 24722957
TI  - A CO(2)-responsive pillar[5]arene: synthesis and self-assembly in water.
AB  - The aggregate morphology of a CO2-responsive pillar[5]arene was reversibly
      controlled between toroid-like assemblies and irregular aggregates by bubbling
      CO2 and N2 repeatedly. 

PMID- 24722958
TI  - Minimally invasive surgery of mitral valve (MIS-MV).
AB  - Following the revision of the therapeutic guideline of ACC/AHA in (Circulation
      114:450-527, 2006), the incidence of mitral valve repair in asymptomatic patients
      with moderate or severe mitral valve regurgitation has increased. For mitral
      valve repair, the quality and outcomes as well as lower invasive procedure are
      important to obtain the confidence of cardiologists and ensure request of early
      phase operation from cardiologists. With recent innovations of technologies and
      the development of revolutionary techniques, minimally invasive surgery of the
      mitral valve (MIS-MV) has become a widespread surgical option of mitral valve
      repair. It is vital, however, that careful preoperative assessment, and planning
      of the approach and perfusion strategy are put in place to perform MIS-MV safely.

PMID- 24722959
TI  - Spontaneous spinal epidural hematoma presenting as paraplegia after cardiac
      surgery.
AB  - An 86-year-old woman was scheduled to undergo aortic valve replacement and
      coronary artery bypass graft. On postoperative day 3, she developed sudden-onset
      neck pain followed by weakness in the right arm. Her symptoms worsened with time,
      and she developed paraplegia. At 60 h after the first complaint, spontaneous
      spinal epidural hematoma (SSEH) from C2 to C6 with spinal cord compression was
      diagnosed from a magnetic resonance image of the cervical region. We decided on
      conservative therapy because operative recovery was impossible. Delayed diagnosis
      led to grievous results in the present case. When neurological abnormalities
      follow neck or back pain after open heart surgery, SSEH must be considered in the
      differential diagnosis. Further, if it is suspected, early cervical computed
      tomography/magnetic resonance imaging and surgery should be considered. 

PMID- 24722960
TI  - Effects of a multiple health behavior change intervention for colorectal cancer
      survivors on psychosocial outcomes and quality of life: a randomized controlled
      trial.
AB  - BACKGROUND: Multiple health behavior change can ameliorate adverse effects of
      cancer. PURPOSE: The purpose of this study was to determine the effects of a
      multiple health behavior change intervention (CanChange) for colorectal cancer
      survivors on psychosocial outcomes and quality of life. METHODS: A total of 410
      colorectal cancer survivors were randomized to a 6-month telephone-based health
      coaching intervention (11 sessions using acceptance and commitment therapy
      strategies focusing on physical activity, weight management, diet, alcohol, and
      smoking) or usual care. Posttraumatic growth, spirituality, acceptance,
      mindfulness, distress, and quality of life were assessed at baseline, 6 and 12
      months. RESULTS: Significant intervention effects were observed for posttraumatic
      growth at 6 (7.5, p < 0.001) and 12 months (4.1, p = 0.033), spirituality at 6
      months (1.8, p = 0.011), acceptance at 6 months (0.2, p = 0.005), and quality of
      life at 6 (0.8, p = 0.049) and 12 months (0.9, p = 0.037). CONCLUSIONS: The
      intervention improved psychosocial outcomes and quality of life (physical well
      being) at 6 months with most effects still present at 12 months. ( TRIAL
      REGISTRATION NUMBER: ACTRN12608000399392).

PMID- 24722962
TI  - Optimizing approaches to addressing depression in cardiac patients: a comment on
      O'Neil et al.

PMID- 24722963
TI  - The critical importance of medication adherence and its assessment: a comment on
      Sutton et Al.

PMID- 24722965
TI  - Fear-avoidance, pain acceptance and adjustment to chronic pain: a cross-sectional
      study on a sample of 686 patients with chronic spinal pain.
AB  - BACKGROUND: Prior studies found a range of psychological factors related to the
      perception of pain, maintenance of pain and disability. PURPOSE: The aim of this
      study was to investigate the role of pain fear-avoidance and pain acceptance in
      chronic pain adjustment. The influence of two diathesis variables (resilience and
      experiential avoidance) was also analyzed. METHODS: The sample was composed of
      686 patients with chronic spinal pain. Structural equation modelling analyses
      were used to test the hypothetical model. RESULTS: Experiential avoidance was
      associated with pain fear-avoidance, and resilience was strongly associated with
      pain acceptance. Pain acceptance was negatively associated with negative mood,
      functional impairment and pain intensity. However, pain fear-avoidance was
      positively and significantly associated with negative mood but had no association
      with pain intensity. There was a path from functional impairment to pain fear
      avoidance. CONCLUSIONS: Resilience and experiential avoidance appear as variables
      which could explain individual differences in pain experience.

PMID- 24722964
TI  - Approaches for informing optimal dose of behavioral interventions.
AB  - BACKGROUND: There is little guidance about to how select dose parameter values
      when designing behavioral interventions. PURPOSE: The purpose of this study is to
      present approaches to inform intervention duration, frequency, and amount when
      (1) the investigator has no a priori expectation and is seeking a descriptive
      approach for identifying and narrowing the universe of dose values or (2) the
      investigator has an a priori expectation and is seeking validation of this
      expectation using an inferential approach. METHODS: Strengths and weaknesses of
      various approaches are described and illustrated with examples. RESULTS:
      Descriptive approaches include retrospective analysis of data from randomized
      trials, assessment of perceived optimal dose via prospective surveys or
      interviews of key stakeholders, and assessment of target patient behavior via
      prospective, longitudinal, observational studies. Inferential approaches include
      nonrandomized, early-phase trials and randomized designs. CONCLUSIONS: By
      utilizing these approaches, researchers may more efficiently apply resources to
      identify the optimal values of dose parameters for behavioral interventions.

PMID- 24722966
TI  - Best practice recommendations for prevention of sudden death in secondary school
      athletes: an update.
AB  - The aim of the recent Inter-Association Task Force held in Washington, D.C. at
      the 2013 Youth Safety Summit determined best practice recommendations for
      preventing sudden death in secondary school athletics. This document highlights
      the major health and safety practices and policies in high school athletics that
      are paramount to keep student athletes safe. The purpose of this commentary is to
      review the findings of the document developed by the task force and to provide
      possible areas where research is needed to continue to educate medical
      practitioners, players, coaches, and parents on ways to prevent tragedies from
      occurring during sport. 

PMID- 24722967
TI  - Traumatic optic neuropathy secondary to posterior subtenon triamcinolone
      acetonide injection in a case with scleritis.

PMID- 24722969
TI  - Molecular characterization of a Chinese isolate of potato virus A (PVA) and
      evidence of a genome recombination event between PVA variants at the 3'-proximal
      end of the genome.
AB  - Potato plants that exhibited mosaic symptoms were collected in Xiangxi, Hunan
      province, China. Multiplex RT-PCR screening for common viruses revealed the
      presence of potato virus A (PVA) in these samples. ELISA with virus-specific
      antibodies confirmed infection by PVA in the plants. Rod-shaped virions of ~750
      nm in length and ~13 nm in width were observed by transmission electron
      microscopy. One virus isolate (designated PVA-Hunan) was subjected to molecular
      characterization. The viral genome consisted of 9,567 nucleotides, excluding the
      poly(A) tail, and encoded a polyprotein of 3,059 amino acids. A second
      characteristic potyvirus open reading frame (ORF), pretty interesting Potyviridae
      ORF (pipo), was located at nucleotides 2,834-3,139. The isolate shared 84% to 98%
      and 93% to 99% sequence identity with other PVA isolates at the nucleotide and
      amino acid level, respectively. Phylogenetic analysis demonstrated that, within
      the PVA group, PVA-Hunan clustered most closely with the Finnish isolate Her,
      then with isolates 143, U, Ali, M and B11. The isolate TamMV stood alone at a
      separate branch. However, scanning of complete genome sequences using SimPlot
      revealed 99%-sequence identity between PVA-Hunan and TamMV in the 3'-proximal end
      of the genome (~nt 9,160 to the 3'end) and a 50%-94% (average~83%) identity
      upstream of nt 9,160. In contrast, 98% identity between PVA-Hunan and isolates M
      and B11 was detected for nucleotides 1 to ~9,160, but only ~94% for the 3'
      proximal region, suggesting a genome recombination event (RE) at nt 9,133. The
      recombination breakpoint also was identified by the Recombination Detection
      Program (RDP). The RE was further confirmed by analysis of the CP gene, where the
      apparent RE was located.

PMID- 24722970
TI  - CNS macrophages and peripheral myeloid cells in brain tumours.
AB  - Primary brain tumours (gliomas) initiate a strong host response and can contain
      large amounts of immune cells (myeloid cells) such as microglia and tumour
      infiltrating macrophages. In gliomas the course of pathology is not only
      controlled by the genetic make-up of the tumour cells, but also depends on the
      interplay with myeloid cells in the tumour microenvironment. Especially malignant
      gliomas such as glioblastoma multiforme (GBM) are notoriously immune-suppressive
      and it is now evident that GBM cells manipulate myeloid cells to support tumour
      expansion. The protumorigenic effects of glioma-associated myeloid cells comprise
      a support for angiogenesis as well as tumour cell invasion, proliferation and
      survival. Different strategies for inhibiting the pathological functions of
      myeloid cells in gliomas are explored, and blocking the tropism of
      microglia/macrophages to gliomas or manipulating the signal transduction pathways
      for immune cell activation has been successful in pre-clinical models. Hence,
      myeloid cells are now emerging as a promising target for new adjuvant therapies
      for gliomas. However, it is also becoming evident that some myeloid-directed
      glioma therapies may only be beneficial for distinct subclasses of gliomas and
      that a more cell-type-specific manipulation of either microglia or macrophages
      may improve therapeutic outcomes. 

PMID- 24722971
TI  - Endogenous estrogen metabolites as biomarkers for endometrial cancer via a novel
      method of liquid chromatography-mass spectrometry with hollow fiber liquid-phase
      microextraction.
AB  - Increased levels of endogenous estrogens and their metabolites are well-known
      risk factors of endometrial cancer. The aim of this study was to quantitatively
      assess the potential for estrogen metabolites to serve as biomarkers of
      endometrial carcinogenesis. The following estrogen metabolites were evaluated: 2
      hydroxyestradiol (2-OHE2), 2-hydroxyestrone (2-OHE1), 4-hydroxyestradiol (4
      OHE2), 4-hydroxyestrone (4-OHE1), 16alpha-hydroxyestrone (16alpha-OHE1), 2
      methoxyestradiol (2-MeOE2), and 2-methoxyestrone (2-MeOE1). The low content of
      estrogen metabolites in urine makes their measurement difficult. To address this
      issue, we developed a rapid, sensitive, specific, and accurate liquid
      chromatography-mass spectrometry (LC-MS) method, with hollow fiber liquid-phase
      micro-extraction (HF-LPME) for an enriched pretreatment of the sample and for the
      simultaneous quantification of estrogens and their metabolites in the urine
      samples of 23 post-menopausal female endometrial cancer patients and 23 post
      menopausal healthy female controls. The levels of estrogens were found to differ
      between the endometrial cancer patients and the controls. The level of 4-OHE2 was
      elevated in patients compared with the controls, while the levels of 2-MeOE1 and
      2-MeOE2 were reduced in the endometrial cancer group. The results of this study
      indicate an imbalance of estrogen metabolites in endometrial carcinogenesis, and
      that the elevation of 4-OHE2 may be used as a potential biomarker for the risk
      assessment of estrogen-induced endometrial cancer. 

PMID- 24722972
TI  - Re: bone: an acute buffer of plasma sodium during exhaustive exercise?

PMID- 24722973
TI  - Relationship of the SAMe-TT2R2 score to poor-quality anticoagulation, stroke,
      clinically relevant bleeding, and mortality in patients with atrial fibrillation.
AB  - BACKGROUND: The efficacy and safety of anticoagulation with use of vitamin K
      antagonists (VKAs) is highly dependent on the quality of anticoagulation control
      as reflected by the average time in a therapeutic range of 2.0 to 3.0. A clinical
      dilemma is trying to predict which anticoagulation-naive patients with atrial
      fibrillation (AF) would do well on a VKA (with a time in therapeutic range > 70%)
      and which are less likely to do well on a VKA but could be managed with novel
      oral anticoagulants. METHODS: The cohort comprised 8,120 patients, among whom
      4,637 patients were receiving VKA. We investigated whether the SAMe-TT2R2 (sex
      female, age < 60 years, medical history [more than two comorbidities], treatment
      [interacting drugs, eg, amiodarone for rhythm control], tobacco use [doubled],
      race [doubled]) score could discriminate among patients with AF who were likely
      to have a labile international normalized ratio (INR) during follow-up as well as
      stroke/thromboembolism (TE), clinically relevant bleeding (defined as severe
      bleeding and as Bleeding Academic Research Consortium [BARC]-defined major
      bleeding), and death while being treated with a VKA. RESULTS: During a mean
      follow-up of 1,016 +/- 1,108 days, there was a significant increase in risk of
      severe bleeding events (risk ratio [RR], 1.38; 95% CI, 1.12-2.68; P = .002) and a
      significant increase in risk of major BARC bleeding (RR, 1.77; 95% CI, 1.29-2.44;
      P = .0005) in patients with AF with a high SAMe-TT2R2 score (> 2). Increasing
      SAMe-TT2R2 score was associated with an increasing risk of labile INR (P = .004),
      stroke/TE (P = .007), severe bleeding (P < .0001), major BARC bleeding (P <
      .0001), and death (P = .002) at follow-up. Among the patients taking VKAs, the
      SAMe-TT2R2 score was predictive of labile INR (C statistic approximately 0.58) as
      well as of stroke/TE, severe bleeding, major BARC bleeding, and death (C
      statistic, 0.54-0.57 for events), reflecting the suboptimal time in therapeutic
      range in such patients. This was not the case for patients who were not taking
      VKAs. CONCLUSIONS: We demonstrate that the SAMe-TT2R2 score was predictive for an
      increasing risk of stroke/TE, severe bleeding, major BARC bleeding, and death,
      reflecting poor anticoagulation control (and labile INRs) among patients with AF
      given VKAs.

PMID- 24722974
TI  - VE1 immunohistochemistry accurately detects BRAF V600E mutations in colorectal
      carcinoma and can be utilized in the detection of poorly differentiated
      colorectal serrated adenocarcinoma.
AB  - Serrated adenocarcinoma (SAC) is a recently defined subtype of colorectal
      carcinoma (CRC). However, in cases where an adjacent serrated adenoma is absent
      and the differentiation is poor, the diagnosis of SAC can be challenging. BRAF
      V600E mutation is a characteristic molecular change for the serrated route, but
      the utility of the newly described BRAF V600E-specific immunohistochemistry in
      the recognition of SAC is unclear. In this study, we conducted
      immunohistochemical determination of BRAF V600E mutation and correlated the
      results to BRAF mutation status and the histological features of SAC in a cohort
      of 147 CRC patients. There were 13 (8.8 %) BRAF-mutated CRCs confirmed by DNA
      sequencing. The sensitivity of immunohistochemistry in detecting BRAF V600E
      mutation was 100 % (13/13) and the specificity was 99.3 % (133/134). Three
      evaluators independently analyzed the immunohistochemical sections and the
      correlation between all the evaluators was perfect (kappa = 1). In histologic
      examination, 33 (22.4 %) of the CRCs were classified as SACs. Twelve of 13 (92.3
      %) BRAF-mutated CRCs were evaluated to represent serrated type growth pattern.
      One of 13 (7.7 %) showed poor differentiation not enabling convincing
      classification. In conclusion, we found immunohistochemistry to be accurate in
      the detection of the BRAF V600E mutation, with potential applications in the
      recognition of the BRAF-mutated SACs. Especially in cases where the adjacent
      adenoma is absent and the tumor is poorly differentiated, BRAF
      immunohistochemistry could be utilized as an aid to detect SACs. 

PMID- 24722975
TI  - Delivering 9-1-1 CPR Instructions to Limited English Proficient Callers: A
      Simulation Experiment.
AB  - Having 911 telecommunicators deliver CPR instructions increases cardiac arrest
      survival, but limited English proficiency (LEP) decreases the likelihood callers
      will perform CPR and increases time to first compression. The objective of our
      study was to assess which 9-1-1 CPR delivery modes could decrease time to first
      compression and improve CPR quality for LEP callers. 139 LEP Spanish and Chinese
      speakers were randomized into three arms: receiving CPR instructions from a 9-1-1
      telecommunicator (1) with telephone interpretation, (2) using alternative, simple
      ways to rephrase, or (3) who strictly adhered to protocol language. Time interval
      from call onset to first compression, and CPR quality were the main outcomes. The
      CPR quality was poor across study arms. Connecting to interpreter services added
      almost 2 min to the time. CPR training in LEP communities, and regular CPR
      training for phone interpreters may be necessary to improve LEP bystander CPR
      quality. 

PMID- 24722980
TI  - The effect of physical training on heart rate variability in healthy children: a
      systematic review with meta-analysis.
AB  - The positive effects of physical training on heart rate variability (HRV) in
      healthy adults are widely recognized; however, the responsiveness to training in
      healthy children has not yet been established. The aim of this study was to
      determine the influence of physical training on HRV in prepubertal healthy
      children. Systematic computerized searches were performed from 1950 to 2012 in
      the following databases: Medline, Embase, Cinahl, Lilacs, Scielo, SportDiscus,
      ProQuest; Web of Science; PEDro; Academic Search Premier and the Cochrane
      Library. The key words used were: heart rate variability, autonomic nervous
      system, exercise training, physical activity, continuous exercise, intermittent
      exercise, children, prepubescent, adolescents, and healthy. Although the database
      search initially identified 6,164 studies, after removing duplicates and
      excluding by title the number was 148, however, only 2 studies were included in
      this systematic review. The meta-analysis compared the experimental group (n =
      29) with the control group (n = 28) for the HRV parameters: RR intervals, SDNN,
      RMSSD, pNN50, LF (log), HF (log), LF/HF and Total Power (log). The meta-analysis
      demonstrated similar HRV indices between both the experimental and control
      groups. In conclusion, the available results from randomized controlled trials do
      not support the hypothesis that physical training improves HRV in healthy
      children[AUQ2]. 

PMID- 24722981
TI  - Defining chemical expansion: the choice of units for the stoichiometric expansion
      coefficient.
AB  - Chemical expansion refers to the spatial dilation of a material that occurs upon
      changes in its composition. When this dilation is caused by a gradual, iso
      structural increase in the lattice parameter with composition, it is related to
      the composition change by the stoichiometric expansion coefficient. In this work,
      three different approaches to defining the stoichiometric expansion coefficient
      (alphaS) are discussed. While all three definitions of alphaS given here are
      legitimate, we show that there are advantages to selecting certain ones for
      comparison across different crystal structures. Examples are provided for changes
      in oxygen content in fluorite, perovskite, and Ruddlesden-Popper (K2NiF4) phase
      materials used in solid oxide fuel cells. 

PMID- 24722982
TI  - Enzyme-based inverse opals: a facile and promising platform for fabrication of
      biocatalysts.
AB  - A facile and promising approach was developed to fabricate enzyme-based 3D
      ordered macroporous biocatalysts (enzyme-based inverse opals) by using the
      colloidal crystal templating method. Horseradish peroxidase- and amylase-based
      inverse opals were prepared, which verified that this method is suitable for
      various enzymes. 

PMID- 24722983
TI  - Synthesis of nitrogen-doped activated graphene aerogel/gold nanoparticles and its
      application for electrochemical detection of hydroquinone and o-dihydroxybenzene.
AB  - Graphene aerogel materials have attracted increasing attention owing to their
      large specific surface area, high conductivity and electronic interactions. Here,
      we report for the first time a novel strategy for the synthesis of nitrogen-doped
      activated graphene aerogel/gold nanoparticles (N-doped AGA/GNs). First, the
      mixture of graphite oxide, 2,4,6-trihydroxybenzaldehyde, urea and potassium
      hydroxide was dispersed in water and subsequently heated to form a graphene oxide
      hydrogel. Then, the hydrogel was dried by freeze-drying and reduced by thermal
      annealing in an Ar/H2 environment in sequence. Finally, GNs were adsorbed on the
      surface of the N-doped AGA. The resulting N-doped AGA/GNs offers excellent
      electronic conductivity (2.8 * 10(3) S m(-1)), specific surface area (1258 m(2)
      g(-1)), well-defined 3D hierarchical porous structure and apparent heterogeneous
      electron transfer rate constant (40.78 +/- 0.15 cm s(-1)), which are notably
      better than that of previous graphene aerogel materials. Moreover, the N-doped
      AGA/GNs was used as a new sensing material for the electrochemical detection of
      hydroquinone (HQ) and o-dihydroxybenzene (DHB). Owing to the greatly enhanced
      electron transfer and mass transport, the sensor displays ultrasensitive
      electrochemical response to HQ and DHB. Its differential pulse voltammetric peak
      current linearly increases with the increase of HQ and DHB in the range of 5.0 *
      10(-8) to 1.8 * 10(-4) M for HQ and 1 * 10(-8) to 2.0 * 10(-4) M for DHB. The
      detection limit is 1.5 * 10(-8) M for HQ and 3.3 * 10(-9) M for DHB (S/N = 3).
      This method provides the advantage of sensitivity, repeatability and stability
      compared with other HQ and DHB sensors. The sensor has been successfully applied
      to detection of HQ and DHB in real water samples with the spiked recovery in the
      range of 96.8-103.2%. The study also provides a promising approach for the
      fabrication of various graphene aerogel materials with improved electrochemical
      performances, which can be potentially applied in biosensors, electrocatalysis,
      and energy storage/conversion devices. 

PMID- 24722984
TI  - Small substrate transport and mechanism of a molybdate ATP binding cassette
      transporter in a lipid environment.
AB  - Embedded in the plasma membrane of all bacteria, ATP binding cassette (ABC)
      importers facilitate the uptake of several vital nutrients and cofactors. The ABC
      transporter, MolBC-A, imports molybdate by passing substrate from the binding
      protein MolA to a membrane-spanning translocation pathway of MolB. To understand
      the mechanism of transport in the biological membrane as a whole, the effects of
      the lipid bilayer on transport needed to be addressed. Continuous wave-electron
      paramagnetic resonance and in vivo molybdate uptake studies were used to test the
      impact of the lipid environment on the mechanism and function of MolBC-A. Working
      with the bacterium Haemophilus influenzae, we found that MolBC-A functions as a
      low affinity molybdate transporter in its native environment. In periods of high
      extracellular molybdate concentration, H. influenzae makes use of parallel
      molybdate transport systems (MolBC-A and ModBC-A) to take up a greater amount of
      molybdate than a strain with ModBC-A alone. In addition, the movement of the
      translocation pathway in response to nucleotide binding and hydrolysis in a lipid
      environment is conserved when compared with in-detergent analysis. However,
      electron paramagnetic resonance spectroscopy indicates that a lipid environment
      restricts the flexibility of the MolBC translocation pathway. By combining
      continuous wave-electron paramagnetic resonance spectroscopy and substrate uptake
      studies, we reveal details of molybdate transport and the logistics of uptake
      systems that employ multiple transporters for the same substrate, offering
      insight into the mechanisms of nutrient uptake in bacteria. 

PMID- 24722985
TI  - The accessory factor Nef links HIV-1 to Tec/Btk kinases in an Src homology 3
      domain-dependent manner.
AB  - The HIV-1 Nef virulence factor interacts with multiple host cell-signaling
      proteins. Nef binds to the Src homology 3 domains of Src family kinases,
      resulting in kinase activation important for viral infectivity, replication, and
      MHC-I down-regulation. Itk and other Tec family kinases are also present in HIV
      target cells, and Itk has been linked to HIV-1 infectivity and replication.
      However, the molecular mechanism linking Itk to HIV-1 is unknown. In this study,
      we explored the interaction of Nef with Tec family kinases using a cell-based
      bimolecular fluorescence complementation assay. In this approach, interaction of
      Nef with a partner kinase juxtaposes nonfluorescent YFP fragments fused to the C
      terminus of each protein, resulting in YFP complementation and a bright
      fluorescent signal. Using bimolecular fluorescence complementation, we observed
      that Nef interacts with the Tec family members Bmx, Btk, and Itk but not Tec or
      Txk. Interaction with Nef occurs through the kinase Src homology 3 domains and
      localizes to the plasma membrane. Allelic variants of Nef from all major HIV-1
      subtypes interacted strongly with Itk in this assay, demonstrating the highly
      conserved nature of this interaction. A selective small molecule inhibitor of Itk
      kinase activity (BMS-509744) potently blocked wild-type HIV-1 infectivity and
      replication, but not that of a Nef-defective mutant. Nef induced constitutive Itk
      activation in transfected cells that was sensitive to inhibitor treatment. Taken
      together, these results provide the first evidence that Nef interacts with
      cytoplasmic tyrosine kinases of the Tec family and suggest that Nef provides a
      mechanistic link between HIV-1 and Itk signaling in the viral life cycle. 

PMID- 24722986
TI  - Assembly of lipopolysaccharide in Escherichia coli requires the essential LapB
      heat shock protein.
AB  - Here, we describe two new heat shock proteins involved in the assembly of LPS in
      Escherichia coli, LapA and LapB (lipopolysaccharide assembly protein A and B).
      lapB mutants were identified based on an increased envelope stress response.
      Envelope stress-responsive pathways control key steps in LPS biogenesis and
      respond to defects in the LPS assembly. Accordingly, the LPS content in DeltalapB
      or Delta(lapA lapB) mutants was elevated, with an enrichment of LPS derivatives
      with truncations in the core region, some of which were pentaacylated and
      exhibited carbon chain polymorphism. Further, the levels of LpxC, the enzyme that
      catalyzes the first committed step of lipid A synthesis, were highly elevated in
      the Delta(lapA lapB) mutant. Delta(lapA lapB) mutant accumulated extragenic
      suppressors that mapped either to lpxC, waaC, and gmhA, or to the waaQ operon
      (LPS biosynthesis) and lpp (Braun's lipoprotein). Increased synthesis of either
      FabZ (3-R-hydroxymyristoyl acyl carrier protein dehydratase), slrA (novel RpoE
      regulated non-coding sRNA), lipoprotein YceK, toxin HicA, or MurA (UDP-N
      acetylglucosamine 1-carboxyvinyltransferase) suppressed some of the Delta(lapA
      lapB) defects. LapB contains six tetratricopeptide repeats and, at the C-terminal
      end, a rubredoxin-like domain that was found to be essential for its activity. In
      pull-down experiments, LapA and LapB co-purified with LPS, Lpt proteins, FtsH
      (protease), DnaK, and DnaJ (chaperones). A specific interaction was also observed
      between WaaC and LapB. Our data suggest that LapB coordinates assembly of
      proteins involved in LPS synthesis at the plasma membrane and regulates turnover
      of LpxC, thereby ensuring balanced biosynthesis of LPS and phospholipids
      consistent with its essentiality. 

PMID- 24722987
TI  - The E3 ubiquitin protein ligase HERC2 modulates the activity of tumor protein p53
      by regulating its oligomerization.
AB  - The tumor suppressor p53 is a transcription factor that coordinates the cellular
      response to several kinds of stress. p53 inactivation is an important step in
      tumor progression. Oligomerization of p53 is critical for its posttranslational
      modification and its ability to regulate the transcription of target genes
      necessary to inhibit tumor growth. Here we report that the HECT E3 ubiquitin
      ligase HERC2 interacts with p53. This interaction involves the CPH domain of
      HERC2 (a conserved domain within Cul7, PARC, and HERC2 proteins) and the last 43
      amino acid residues of p53. Through this interaction, HERC2 regulates p53
      activity. RNA interference experiments showed how HERC2 depletion reduces the
      transcriptional activity of p53 without affecting its stability. This regulation
      of p53 activity by HERC2 is independent of proteasome or MDM2 activity. Under
      these conditions, up-regulation of cell growth and increased focus formation were
      observed, showing the functional relevance of the HERC2-p53 interaction. This
      interaction was maintained after DNA damage caused by the chemotherapeutic drug
      bleomycin. In these stressed cells, p53 phosphorylation was not impaired by HERC2
      knockdown. Interestingly, p53 mutations that affect its tetramerization domain
      disrupted the HERC2-p53 interaction, suggesting a role for HERC2 in p53
      oligomerization. This regulatory role was shown using cross-linking assays. Thus,
      the inhibition of p53 activity after HERC2 depletion can be attributed to a
      reduction in p53 oligomerization. Ectopic expression of HERC2 (residues 2292
      2923) confirmed these observations. Together, these results identify HERC2 as a
      novel regulator of p53 signaling. 

PMID- 24722988
TI  - Identification of 5' AMP-activated kinase as a target of reactive aldehydes
      during chronic ingestion of high concentrations of ethanol.
AB  - The production of reactive aldehydes including 4-hydroxy-2-nonenal (4-HNE) is a
      key component of the pathogenesis in a spectrum of chronic inflammatory hepatic
      diseases including alcoholic liver disease (ALD). One consequence of ALD is
      increased oxidative stress and altered beta-oxidation in hepatocytes. A major
      regulator of beta-oxidation is 5' AMP protein kinase (AMPK). In an in vitro
      cellular model, we identified AMPK as a direct target of 4-HNE adduction
      resulting in inhibition of both H2O2 and 5-aminoimidazole-4-carboxyamide
      ribonucleoside (AICAR)-induced downstream signaling. By employing biotin
      hydrazide capture, it was confirmed that 4-HNE treatment of cells resulted in
      carbonylation of AMPKalpha/beta, which was not observed in untreated cells. Using
      a murine model of alcoholic liver disease, treatment with high concentrations of
      ethanol resulted in an increase in phosphorylated as well as carbonylated
      AMPKalpha. Despite increased AMPK phosphorylation, there was no significant
      change in phosphorylation of acetyl CoA carboxylase. Mass spectrometry identified
      Michael addition adducts of 4-HNE on Cys(130), Cys(174), Cys(227), and Cys(304)
      on recombinant AMPKalpha and Cys(225) on recombinant AMPKbeta. Molecular modeling
      analysis of identified 4-HNE adducts on AMPKalpha suggest that inhibition of AMPK
      occurs by steric hindrance of the active site pocket and by inhibition of
      hydrogen peroxide induced oxidation. The observed inhibition of AMPK by 4-HNE
      provides a novel mechanism for altered beta-oxidation in ALD, and these data
      demonstrate for the first time that AMPK is subject to regulation by reactive
      aldehydes in vivo. 

PMID- 24722989
TI  - Guanine nucleotide-binding protein (Galpha) endocytosis by a cascade of ubiquitin
      binding domain proteins is required for sustained morphogenesis and proper mating
      in yeast.
AB  - Heterotrimeric G proteins are well known to transmit signals from cell surface
      receptors to intracellular effector proteins. There is growing appreciation that
      G proteins are also present at endomembrane compartments, where they can
      potentially interact with a distinct set of signaling proteins. Here, we examine
      the cellular trafficking function of the G protein alpha subunit in yeast, Gpa1.
      Gpa1 contains a unique 109-amino acid insert within the alpha-helical domain that
      undergoes a variety of posttranslational modifications. Among these is
      monoubiquitination, catalyzed by the NEDD4 family ubiquitin ligase Rsp5. Using a
      newly optimized method for G protein purification together with biophysical
      measures of structure and function, we show that the ubiquitination domain does
      not influence enzyme activity. By screening a panel of 39 gene deletion mutants,
      each lacking a different ubiquitin binding domain protein, we identify seven that
      are necessary to deliver Gpa1 to the vacuole compartment including four proteins
      (Ede1, Bul1, Ddi1, and Rup1) previously not known to be involved in this process.
      Finally, we show that proper endocytosis of the G protein is needed for sustained
      cellular morphogenesis and mating in response to pheromone stimulation. We
      conclude that a cascade of ubiquitin-binding proteins serves to deliver the G
      protein to its final destination within the cell. In this instance and in
      contrast to the previously characterized visual system, endocytosis from the
      plasma membrane is needed for proper signal transduction rather than for signal
      desensitization. 

PMID- 24722990
TI  - Nicotinamide nucleotide transhydrogenase (Nnt) links the substrate requirement in
      brain mitochondria for hydrogen peroxide removal to the thioredoxin/peroxiredoxin
      (Trx/Prx) system.
AB  - Mitochondrial reactive oxygen species are implicated in the etiology of multiple
      neurodegenerative diseases, including Parkinson disease. Mitochondria are known
      to be net producers of ROS, but recently we have shown that brain mitochondria
      can consume mitochondrial hydrogen peroxide (H2O2) in a respiration-dependent
      manner predominantly by the thioredoxin/peroxiredoxin system. Here, we sought to
      determine the mechanism linking mitochondrial respiration with H2O2 catabolism in
      brain mitochondria and dopaminergic cells. We hypothesized that nicotinamide
      nucleotide transhydrogenase (Nnt), which utilizes the proton gradient to generate
      NADPH from NADH and NADP(+), provides the link between mitochondrial respiration
      and H2O2 detoxification through the thioredoxin/peroxiredoxin system.
      Pharmacological inhibition of Nnt in isolated brain mitochondria significantly
      decreased their ability to consume H2O2 in the presence, but not absence, of
      respiration substrates. Nnt inhibition in liver mitochondria, which do not
      require substrates to detoxify H2O2, had no effect. Pharmacological inhibition or
      lentiviral knockdown of Nnt in N27 dopaminergic cells (a) decreased H2O2
      catabolism, (b) decreased NADPH and increased NADP(+) levels, and (c) decreased
      basal, spare, and maximal mitochondrial oxygen consumption rates. Nnt-deficient
      cells possessed higher levels of oxidized mitochondrial Prx, which rendered them
      more susceptible to steady-state increases in H2O2 and cell death following
      exposure to subtoxic levels of paraquat. These data implicate Nnt as the critical
      link between the metabolic and H2O2 antioxidant function in brain mitochondria
      and suggests Nnt as a potential therapeutic target to improve the redox balance
      in conditions of oxidative stress associated with neurodegenerative diseases. 

PMID- 24722991
TI  - Diversity in guanosine 3',5'-bisdiphosphate (ppGpp) sensitivity among guanylate
      kinases of bacteria and plants.
AB  - The guanosine 3',5'-bisdiphosphate (ppGpp) signaling system is shared by bacteria
      and plant chloroplasts, but its role in plants has remained unclear. Here we show
      that guanylate kinase (GK), a key enzyme in guanine nucleotide biosynthesis that
      catalyzes the conversion of GMP to GDP, is a target of regulation by ppGpp in
      chloroplasts of rice, pea, and Arabidopsis. Plants have two distinct types of GK
      that are localized to organelles (GKpm) or to the cytosol (GKc), with both
      enzymes being essential for growth and development. We found that the activity of
      rice GKpm in vitro was inhibited by ppGpp with a Ki of 2.8 MUM relative to the
      substrate GMP, whereas the Km of this enzyme for GMP was 73 MUM. The IC50 of
      ppGpp for GKpm was ~10 MUM. In contrast, the activity of rice GKc was insensitive
      to ppGpp, as was that of GK from bakers' yeast, which is also a cytosolic enzyme.
      These observations suggest that ppGpp plays a pivotal role in the regulation of
      GTP biosynthesis in chloroplasts through specific inhibition of GKpm activity,
      with the regulation of GTP biosynthesis in chloroplasts thus being independent of
      that in the cytosol. We also found that GKs of Escherichia coli and Synechococcus
      elongatus PCC 7942 are insensitive to ppGpp, in contrast to the ppGpp sensitivity
      of the Bacillus subtilis enzyme. Our biochemical characterization of GK enzymes
      has thus revealed a novel target of ppGpp in chloroplasts and has uncovered
      diversity among bacterial GKs with regard to regulation by ppGpp.

PMID- 24722992
TI  - Phosphorylation of Arabidopsis ubiquitin ligase ATL31 is critical for plant
      carbon/nitrogen nutrient balance response and controls the stability of 14-3-3
      proteins.
AB  - Ubiquitin ligase plays a fundamental role in regulating multiple cellular events
      in eukaryotes by fine-tuning the stability and activity of specific target
      proteins. We have previously shown that ubiquitin ligase ATL31 regulates plant
      growth in response to nutrient balance between carbon and nitrogen (C/N) in
      Arabidopsis. Subsequent study demonstrated that ATL31 targets 14-3-3 proteins for
      ubiquitination and modulates the protein abundance in response to C/N-nutrient
      status. However, the underlying mechanism for the targeting of ATL31 to 14-3-3
      proteins remains unclear. Here, we show that ATL31 interacts with 14-3-3 proteins
      in a phosphorylation-dependent manner. We identified Thr(209), Ser(247),
      Ser(270), and Ser(303) as putative 14-3-3 binding sites on ATL31 by motif
      analysis. Mutation of these Ser/Thr residues to Ala in ATL31 inhibited the
      interaction with 14-3-3 proteins, as demonstrated by yeast two-hybrid and co
      immunoprecipitation analyses. Additionally, we identified in vivo phosphorylation
      of Thr(209) and Ser(247) on ATL31 by MS analysis. A peptide competition assay
      showed that the application of synthetic phospho-Thr(209) peptide, but not the
      corresponding unphosphorylated peptide, suppresses the interaction between ATL31
      and 14-3-3 proteins. Moreover, Arabidopsis plants overexpressing mutated ATL31,
      which could not bind to 14-3-3 proteins, showed accumulation of 14-3-3 proteins
      and growth arrest in disrupted C/N-nutrient conditions similar to wild-type
      plants, although overexpression of intact ATL31 resulted in repression of 14-3-3
      accumulation and tolerance to the conditions. Together, these results demonstrate
      that the physiological role of phosphorylation at 14-3-3 binding sites on ATL31
      is to modulate the binding ability and stability of 14-3-3 proteins to control
      plant C/N-nutrient response. 

PMID- 24722993
TI  - Follow-up of probably benign lesions in non-screening breast diagnostics.
AB  - PURPOSE: Our study addresses at the benefit of surveillance of probably benign
      lesions, detected outside mammographic screening, during a 3-year period.
      METHODS: 28,588 women (mean age 57 +/- 12 years) were examined. Two independent
      radiologists read the mammogram as well as the supplemented ultrasound (in case
      of breast density ACR type 3 and 4). In the case of discordance a third expert
      considered whether further examination was indicated or not. RESULTS: 3,266
      diagnostic procedures ended with BI-RADS 3 result and 2,512 (76.9 %) women
      underwent a follow-up examination. 295 (11.7 %) of them received assessment
      examination (imaging and/or biopsy) and 37 (12.5 %) (none of them palpable) ended
      with BI-RADS 6. This equals a tumor detection rate of 14.7/1,000. The ratio in
      situ:invasive was 7:10 (1:1.43) and the mean size was 11.1 +/- 4.51 mm. In the
      total cohort, 536 carcinomas ended with BI-RADS 6 of them 17 % were in situ and
      83 % were invasive breast cancers (ratio in situ:invasive 1:4.99), mean size was
      13.8 +/- 6.3 mm. The cancer detection ratio in these cases was 18.7/1,000.
      CONCLUSIONS: The amount of detected tumors at follow-up of women with preceding
      BI-RADS 3 equates the associated potential of malignancy.

PMID- 24722994
TI  - Bis-Fe(IV): nature's sniper for long-range oxidation.
AB  - Iron-dependent enzymes are prevalent in nature and participate in a wide range of
      biological redox activities. Frequently, high-valence iron intermediates are
      involved in the catalytic events of iron-dependent enzymes, especially when the
      activation of peroxide or molecular oxygen is involved. Building on the
      fundamental framework of iron-oxygen chemistry, these reactive intermediates
      constantly attract significant attention from the enzymology community. During
      the past few decades, tremendous efforts from a number of laboratories have been
      dedicated to the capture and characterization of these intermediates to improve
      mechanistic understandings. In 2008, an unprecedented bis-Fe(IV) intermediate was
      reported in a c-type diheme enzyme, MauG, which is involved in the maturation of
      a tryptophan tryptophylquinone cofactor of methylamine dehydrogenase. This
      intermediate, although chemically equivalent to well-characterized high-valence
      iron intermediates, such as compound I, compound ES, and intermediate Q in
      methane monooxygenase, as well as the hypothetical Fe(V) species in Rieske non
      heme oxygenases, is orders of magnitude more stable than these other high-valence
      species in the absence of its primary substrate. It has recently been discovered
      that the bis-Fe(IV) intermediate exhibits a unique near-IR absorption feature
      which has been attributed to a novel charge-resonance phenomenon. This review
      compares the properties of MauG with structurally related enzymes, summarizes the
      current knowledge of this new high-valence iron intermediate, including its
      chemical origin and structural basis, explores the formation and consequences of
      charge resonance, and recounts the long-range catalytic mechanism in which bis
      Fe(IV) participates. Biological strategies for storing oxidizing equivalents with
      iron ions are also discussed. 

PMID- 24722995
TI  - PBMC and exosome-derived Hotair is a critical regulator and potent marker for
      rheumatoid arthritis.
AB  - Despite growing importance of long non-coding RNAs (lncRNAs) in normal
      physiological and disease conditions, our knowledge of RA-related lncRNAs remains
      limited. Therefore, we aimed to identify lncRNA signatures that have prognostic
      values in RA. There was a notably high expression level of Hotair in blood
      mononuclear cells and serum exosome of rheumatoid arthritis (RA) patients,
      leading the migration of active macrophage. In contrast, markedly lower level of
      Hotair was detected in differentiated osteoclasts and rheumatoid synoviocytes and
      enforced expression of Hotair led to significantly decreased levels of MMP-2 and
      MMP-13. This exploratory study provides novel empirical evidence that Hotair
      could be one of potential biomarkers for diagnosing RA. 

PMID- 24722996
TI  - Filgrastim, lenograstim and pegfilgrastim in the mobilization of peripheral blood
      progenitor cells in patients with lymphoproliferative malignancies.
AB  - Patients with lymphoproliferative disorders, candidate to autologous stem cell
      transplantation (ASCT), require mobilization with chemotherapy and granulocyte
      colony -stimulating factor (G-CSF). This study looked for differences in
      hematopoietic peripheral stem cells (HPSCs) mobilization in response to the three
      available G-CSFs, namely lenograstim, filgrastim, and pegfilgrastim. Between 2000
      and 2012, 146 patients (66 M and 80 F) who underwent ASCT for multiple myeloma,
      non-Hodgkin's lymphoma or Hodgkin's lymphoma were studied. All patients received
      induction therapy and then a mobilization regimen with cyclophosphamide plus
      lenograstim, or filgrastim, or pegfilgrastim. From days 12 to 14, HPSCs were
      collected by two to three daily leukaphereses. Our results show that high-dose
      cyclophosphamide plus lenograstim achieved adequate mobilization and the
      collection target more quickly and with fewer leukaphereses as compared to
      filgrastim and pegfilgrastim. No differences between the three regimens were
      observed regarding toxicity and days to WBC and platelet recovery. Thus,
      lenograstim may represent the ideal G-CSF for PBSC mobilization in patients with
      lymphoproliferative diseases. Further studies are needed to confirm these results
      and better understand the biological bases of these differences.

PMID- 24722998
TI  - Re: "Type 2 diabetes and the risk of colorectal adenomas: Black Women's Health
      Study".

PMID- 24722997
TI  - Physical activity across adulthood in relation to fat and lean body mass in early
      old age: findings from the Medical Research Council National Survey of Health and
      Development, 1946-2010.
AB  - Fat and lean body mass have important implications for health and physical
      functioning in older age, and physical activity is purported to be an important
      modifiable determinant. However, our evidence-based understanding of its role is
      limited. We examined the associations of physical activity, assessed both by self
      report (using data on leisure time physical activity (LTPA) collected on 4
      occasions over a 28-year period) and objectively (using 5-day heart rate and
      movement monitoring), with fat and lean mass at ages 60-64 years in 1,162 British
      participants from the Medical Research Council National Survey of Health and
      Development in 1946-2010. Higher objectively assessed physical activity energy
      expenditure (PAEE) at ages 60-64 years was associated with lower fat mass and
      android (abdominal):gynoid (hip) fat ratio (mean differences in fat mass per 1
      standard deviation increase in PAEE were -0.79 kg/m(1.2) in men (95% confidence
      interval: -1.08, -0.50) and -1.79 kg/m(1.2) (95% confidence interval: -2.15, 
      1.42) in women). After adjustment for fat mass, higher PAEE was associated with
      higher appendicular lean mass. Both light and moderate-to-vigorous intensities of
      activity were associated with fat mass, and the latter was associated with lean
      mass. More frequent LTPA across adulthood was associated with lower fat mass (in
      women only) and higher appendicular lean mass (in both sexes, after adjustment
      for fat mass). These results support the promotion of LTPA across adulthood, as
      well as both light and moderate-to-vigorous intensities of activity among older
      adults.

PMID- 24723000
TI  - Methods of estimating or accounting for neighborhood associations with health
      using complex survey data.
AB  - Reasons for health disparities may include neighborhood-level factors, such as
      availability of health services, social norms, and environmental determinants, as
      well as individual-level factors. Investigating health inequalities using
      nationally or locally representative data often requires an approach that can
      accommodate a complex sampling design, in which individuals have unequal
      probabilities of selection into the study. The goal of the present article is to
      review and compare methods of estimating or accounting for neighborhood
      influences with complex survey data. We considered 3 types of methods, each
      generalized for use with complex survey data: ordinary regression, conditional
      likelihood regression, and generalized linear mixed-model regression. The
      relative strengths and weaknesses of each method differ from one study to
      another; we provide an overview of the advantages and disadvantages of each
      method theoretically, in terms of the nature of the estimable associations and
      the plausibility of the assumptions required for validity, and also practically,
      via a simulation study and 2 epidemiologic data analyses. The first analysis
      addresses determinants of repeat mammography screening use using data from the
      2005 National Health Interview Survey. The second analysis addresses disparities
      in preventive oral health care using data from the 2008 Florida Behavioral Risk
      Factor Surveillance System Survey.

PMID- 24722999
TI  - Prenatal exposure to dichlorodiphenyltrichloroethane and obesity at 9 years of
      age in the CHAMACOS study cohort.
AB  - In-utero exposure to endocrine-disrupting compounds, including
      dichlorodiphenyltrichloroethane (DDT) and its metabolite dichlorodiphenylethylene
      (DDE), has been hypothesized to increase the risk of obesity later in life. We
      examined the associations of maternal serum concentrations of DDT and DDE during
      pregnancy with body mass index, obesity, waist circumference, and percentage of
      body fat in 9-year-old children (n = 261) in the Center for the Health Assessment
      of Mothers and Children of Salinas (CHAMACOS) Study, a longitudinal birth cohort
      study in the Salinas Valley, California (2000-2010). We found associations
      between prenatal exposure to DDT and DDE and several measures of obesity at 9
      years of age in boys but not in girls. For example, among boys, 10-fold increases
      in prenatal DDT and DDE concentrations were associated with increased odds of
      becoming overweight or obese (for o,p'-DDT, adjusted odds ratio (OR) = 2.5, 95%
      confidence interval (CI): 1.0, 6.3; for p,p'-DDT, adjusted OR = 2.1, 95% CI: 1.0,
      4.5; and for p,p'-DDE, adjusted OR = 1.97, 95% CI: 0.94, 4.13). The odds ratios
      for girls were nonsignificant. Results were similar for body mass index z score,
      waist circumference z score, and odds of increased waist circumference but were
      less consistent for percentage of body fat. The difference by sex persisted after
      considering pubertal status. These results provide support for the chemical
      obesogen hypothesis. 

PMID- 24723001
TI  - Re: "Type 2 diabetes and the risk of colorectal adenomas: Black Women's Health
      Study". Four authors reply.

PMID- 24723002
TI  - Robust estimation for secondary trait association in case-control genetic
      studies.
AB  - Secondary trait genetic association provides insight into the genetic
      architecture of disease etiology but requires caution in estimation. Ignoring
      case-control sampling may introduce bias into secondary trait association. In
      this paper, we compare the efficiency and robustness of various inverse
      probability weighted (IPW) estimators and maximum likelihood (ML) estimators. ML
      methods have been proposed but require correct modeling of both the secondary and
      the primary trait associations for valid inference. We show that ML methods using
      a misspecified primary trait model can severely inflate the type I error. IPW
      estimators are typically less efficient than ML estimators but are robust against
      model misspecification. When the secondary trait is available for the entire
      cohort, the IPW estimator with selection probabilities estimated
      nonparametrically and the augmented IPW estimator improve efficiency over the
      simple IPW estimator. We conclude that in large genetic association studies with
      complex sampling schemes, IPW-based estimators offer flexibility and robustness,
      and therefore are a viable option for analysis.

PMID- 24723004
TI  - Long-term outcomes following development of new-onset atrial fibrillation during
      sepsis.
AB  - BACKGROUND: New-onset atrial fibrillation (AF) is associated with adverse
      outcomes during a sepsis hospitalization; however, long-term outcomes following
      hospitalization with sepsis-associated new-onset AF are unclear. METHODS: We used
      a Medicare 5% sample to identify patients who survived hospitalization with
      sepsis between 1999 and 2010. AF status was defined as no AF, prior AF, or new
      onset AF based on AF claims during and prior to a sepsis hospitalization. We used
      competing risk models to determine 5-year risks of AF occurrence, heart failure,
      ischemic stroke, and mortality after the sepsis hospitalization, according to AF
      status during the sepsis admission. RESULTS: We identified 138,722 sepsis
      survivors, of whom 95,536 (69%) had no AF during sepsis, 33,646 (24%) had prior
      AF, and 9,540 (7%) had new-onset AF during sepsis. AF occurrence following sepsis
      hospitalization was more common among patients with new-onset AF during sepsis
      (54.9%) than in patients with no AF during sepsis (15.5%). Compared with patients
      with no AF during sepsis, those with new-onset AF during sepsis had greater 5
      year risks of hospitalization for heart failure (11.2% vs 8.2%; multivariable
      adjusted hazard ratio [HR], 1.25; 95% CI, 1.16-1.34), ischemic stroke (5.3% vs
      4.7%; HR, 1.22; 95% CI, 1.10-1.36), and death (74.8% vs 72.1%; HR, 1.04; 95%
      CI,1.01-1.07). CONCLUSIONS: Most sepsis survivors with new-onset AF during sepsis
      have AF occur after discharge from the sepsis hospitalization and have increased
      long-term risks of heart failure, ischemic stroke, and death. Our findings may
      have implications for posthospitalization surveillance of patients with new-onset
      AF during a sepsis hospitalization.

PMID- 24723003
TI  - The relationship between electrocardiographic changes and CMR features in
      asymptomatic or mildly symptomatic patients with hypertrophic cardiomyopathy.
AB  - To investigate the relationship between electrocardiographic (ECG) abnormalities
      and left ventricular (LV) segmental hypertrophy and myocardial fibrosis assessed
      by cardiovascular magnetic resonance (CMR) in asymptomatic or mildly symptomatic
      patients with hypertrophic cardiomyopathy (HCM). 118 asymptomatic or mildly
      symptomatic patients with HCM were examined with late gadolinium enhancement
      (LGE) CMR, 12-lead ECG, and echocardiography. The distribution and magnitude of
      LV segmental hypertrophy and LGE were assessed and analyzed in relation to ECG
      abnormalities. Abnormal electrocardiograms were found in 113 of 118 (95%)
      patients. Negative T waves were associated with greater apical septal thickness
      (P = 0.009) and an increased ratio of LV septum to free wall thickness (P =
      0.01). Giant negative T waves (GNT) were found in 19 patients (16%), and were
      associated with apical HCM (P < 0.001), greater apical thickness (P = 0.004), and
      increased ratio of LV apical to basal wall thickness (P < 0.001). However, no
      significant association was demonstrated between GNT and apical LGE (P = 0.71).
      Abnormal Q waves were associated with greater basal anteroseptal thickness (P =
      0.001), maximal basal thickness (P = 0.004), and more segments with extensive LGE
      (>75% wall thickness involved) (P = 0.001). LV hypertrophy was related to greater
      LV mass (P = 0.002) and LV end diastolic volume (P = 0.002). In addition, a
      modest but significant correlation was observed between maximum LV wall thickness
      and the Romhilt-Estes score (r = 0.41, P < 0.001). GNT were associated with
      apical HCM and an increased ratio of LV apical to basal wall thickness. Abnormal
      Q waves were related to basal anteroseptal hypertrophy and segmental extensive
      LGE.

PMID- 24723005
TI  - The role of mechanical impact in action-related auditory attenuation.
AB  - A number of studies have shown that sounds temporally close to one's own finger
      movements elicit lower-amplitude auditory event-related potentials (ERPs) than do
      the same tones when they are only listened to. In these studies, the actions have
      involved making a mechanical contact with an object. In the present study, the
      role of mechanical contact with an object was investigated in action-related
      auditory attenuation. In three experiments, participants performed a time
      interval production task. In each experiment, in one condition the action
      involved touching an object, but no mechanical contact was made in the other. The
      estimated tone-related ERP contributions to the action-tone coincidence ERP
      waveforms (calculated by subtracting the action-related ERP from the coincidence
      ERP) were more attenuated when the action involved moving the finger and making a
      mechanical contact at the end of the movement. However, when participants kept
      their finger on a piezoelectric element and applied pressure impulses without
      moving their finger, the action did not result in stronger attenuation of the
      tone-related auditory ERP estimates. Although these results may suggest that
      auditory ERP attenuation is stronger for actions resulting in mechanical impact,
      they also imply that mechanical impact may confound and lead to the
      overestimation of auditory ERP attenuation in such paradigms, because the impact
      may result in faint but audible sounds. 

PMID- 24723006
TI  - Prevalence of depression in patients with type 2 diabetes mellitus in Irish
      primary care and the impact of depression on the control of diabetes.
AB  - BACKGROUND: As the Irish population ages, the management of chronic conditions in
      primary care is emerging as a challenge. The presence of co-morbid depression is
      common among such patients and may affect their response to treatment. AIMS: This
      study sought to determine whether the prevalence of depression is higher in
      patients with type 2 diabetes mellitus than in the population aged >50 in the
      West of Ireland, and whether depression is an independent predictor of diabetes
      control. METHODS: We used a cross-sectional design to examine an anonymized
      database of 9,698 patients aged >50 years whose medical data were collected as
      part of NUI Galway's CLARITY study. Glycosylated HbA1c levels were used to
      estimate type 2 DM control; depression was assessed using the Hospital Anxiety
      and Depression Scale. RESULTS: We found that while there is a higher prevalence
      of severe depression in patients with type 2 DM, there is no association between
      their diabetes control and depression after controlling for age, gender,
      comorbidity and GMS status. Multimorbidity is a significant predictor of
      depression in both diabetic and non-diabetic populations, with the odds of
      depression increasing as the number of co-morbidities increased. CONCLUSIONS:
      Patients with type 2 DM are more likely to suffer from severe depression than
      those without. Depression itself is not an independent predictor of diabetes
      control. However, it may be that the increased rates of depression observed in
      patients with type 2 DM are at least partially attributable to the burden of
      additional illnesses seen in these patients.

PMID- 24723008
TI  - Random-close packing limits for monodisperse and polydisperse hard spheres.
AB  - We investigate how the densities of inherent structures, which we refer to as the
      closest jammed configurations, are distributed for packings of 10(4) frictionless
      hard spheres. A computational algorithm is introduced to generate closest jammed
      configurations and determine corresponding densities. Closest jamming densities
      for monodisperse packings generated with high compression rates using Lubachevsky
      Stillinger and force-biased algorithms are distributed in a narrow density range
      from phi = 0.634-0.636 to phi~ 0.64; closest jamming densities for monodisperse
      packings generated with low compression rates converge to phi~ 0.65 and grow
      rapidly when crystallization starts with very low compression rates. We interpret
      phi~ 0.64 as the random-close packing (RCP) limit and phi~ 0.65 as a lower bound
      of the glass close packing (GCP) limit, whereas phi = 0.634-0.636 is attributed
      to another characteristic (lowest typical, LT) density phiLT. The three
      characteristic densities phiLT, phiRCP, and phiGCP are determined for
      polydisperse packings with log-normal sphere radii distributions. 

PMID- 24723007
TI  - Antiplasmodial and antioxidant isoquinoline alkaloids from Dehaasia
      longipedicellata.
AB  - The crude extract of the bark of Dehaasia longipedicellata exhibited
      antiplasmodial activity against the growth of Plasmodium falciparum K1 isolate
      (resistant strain). Phytochemical studies of the extract led to the isolation of
      six alkaloids: two morphinandienones, (+)-sebiferine (1) and (-)-milonine (2);
      two aporphines, (-)-boldine (3) and (-)-norboldine (4); one benzlyisoquinoline, (
      )-reticuline (5); and one bisbenzylisoquinoline, (-)-O-O-dimethylgrisabine (6).
      Their structures were determined on the basis of 1D and 2D NMR, IR, UV, and LCMS
      spectroscopic techniques and upon comparison with literature values.
      Antiplasmodial activity was determined for all of the isolated compounds. They
      showed potent to moderate activity with IC50 values ranging from 0.031 to 30.40
      uM. (-)-O-O-dimethylgrisabine (6) and (-)-milonine (2) were the two most potent
      compounds, with IC50 values of 0.031 and 0.097 uM, respectively, that were
      comparable to the standard, chloroquine (0.090 uM). The compounds were also
      assessed for their antioxidant activities with di(phenyl)-(2,4,6
      trinitrophenyl)iminoazanium (IC50 = 18.40-107.31 ug/mL), reducing power (27.40
      87.40 %), and metal chelating (IC50 = 64.30 to 257.22 ug/mL) having good to low
      activity. (-)-O-O-dimethylgrisabine (6) exhibited a potent antioxidant activity
      of 44.3 % reducing power, while di(phenyl)-(2,4,6-trinitrophenyl)iminoazanium and
      metal chelating activities had IC50 values of 18.38 and 64.30 ug/mL,
      respectively. Thus it may be considered as a good reductant with the ability to
      chelate metal and prevent pro-oxidant activity. In addition to the antiplasmodial
      and antioxidant activities, the isolated compounds were also tested for their
      cytotoxicity against a few cancer and normal cell lines. (-)-Norboldine (4)
      exhibited potent cytotoxicity towards pancreatic cancer cell line BxPC-3 with an
      IC50 value of 27.060 +/- 1.037 uM, and all alkaloids showed no toxicity towards
      the normal pancreatic cell line (hTERT-HPNE). 

PMID- 24723009
TI  - Effect of ocriplasmin on the management of macular holes: assessment of the
      clinical relevance of ocriplasmin.
AB  - IMPORTANCE: Assessing the effect of ocriplasmin availability on the management of
      full-thickness macular holes (MHs) is important for vitreoretinal surgeons and
      their patients. Such an assessment can indicate whether the use of ocriplasmin
      will bring a paradigm shift in treating MHs or will be just an additional option
      relevant to a small group of patients. OBJECTIVES: To classify the MHs evaluated
      in our institute by their stage and the presence of vitreomacular adhesion (VMA)
      and to identify eyes that were suitable candidates for ocriplasmin injection
      according to guidelines published by the Microplasmin for Intravitreous Injection
      Traction Release Without Surgical Treatment (MIVI-TRUST) study group. DESIGN,
      SETTING, AND PARTICIPANTS: All optical coherence tomographic studies of eyes with
      MHs performed between 2009 and 2013 were retrospectively reviewed. The scans were
      interpreted by 2 individuals, and for each hole the stage, size, and
      vitreomacular relationship were defined according to the definitions used in the
      MIVI-TRUST studies. One hundred thirty-five patients with full-thickness MHs
      evaluated at a public hospital were included in the study series. There were 82
      women and 53 men, and the mean (SD) age was 67.3 (12.8) years. MAIN OUTCOMES AND
      MEASURES: The stage, size, and presence or absence of VMA were documented for
      each MH. The suitability for ocriplasmin intravitreal injection was determined
      according to the criteria described in the MIVI-TRUST reports. RESULTS:
      Vitreomacular adhesion was present in 19 eyes with MH (14.1%). Of these, the hole
      size was 400 MUm or less in only 9 eyes (6.7% of the series). Using the criteria
      of the MIVI-TRUST study exclusively, only these eyes were candidates for
      ocriplasmin injection. Assuming a closure success rate of 40%, as described in
      that study, only 2.7% of the patients in our series would have benefited from
      ocriplasmin injection. CONCLUSIONS AND RELEVANCE: Our findings indicate that
      ocriplasmin injection is an adequate choice for few patients with MHs. Pars plana
      vitrectomy will probably remain the treatment of choice for most eyes with MHs.
      This situation could change if MHs are detected earlier and treated while they
      are still small and have vitreomacular traction.

PMID- 24723010
TI  - Semantic support and parallel parsing in Chinese.
AB  - Two eye-tracking experiments were conducted using written Chinese sentences that
      contained a multi-word ambiguous region. The goal was to determine whether
      readers maintained multiple interpretations throughout the ambiguous region or
      selected a single interpretation at the point of ambiguity. Within the ambiguous
      region, we manipulated the strength of support for the complement clause (CC)
      analysis and the relative clause (RC) analysis of the ambiguous construction Verb
      NP1 de NP2. In Experiment 1, the critical sentences were disambiguated to the
      dispreferred CC interpretation; in Experiment 2, the sentences were disambiguated
      as the preferred RC interpretation. Unsurprisingly, processing difficulty at the
      point of disambiguation was observed only in Experiment 1. As predicted by a
      parallel mechanism, greater processing difficulty arose at disambiguation when
      the RC interpretation was much more strongly supported by semantic cues relative
      to the CC alternative, than when the two analyses were semantically supported to
      a similar degree. Regression analyses confirmed that the degree of semantic
      support predicted processing difficulty at disambiguation. The findings provide
      evidence for a parallel constraint-based parsing mechanism. 

PMID- 24723011
TI  - Macro-/micro-environment-sensitive chemosensing and biological imaging.
AB  - Environment-related parameters, including viscosity, polarity, temperature,
      hypoxia, and pH, play pivotal roles in controlling the physical or chemical
      behaviors of local molecules. In particular, in a biological environment, such
      factors predominantly determine the biological properties of the local
      environment or reflect corresponding status alterations. Abnormal changes in
      these factors would cause cellular malfunction or become a hallmark of the
      occurrence of severe diseases. Therefore, in recent years, they have increasingly
      attracted research interest from the fields of chemistry and biological
      chemistry. With the emergence of fluorescence sensing and imaging technology,
      several fluorescent chemosensors have been designed to respond to such parameters
      and to further map their distributions and variations in vitro/in vivo. In this
      work, we have reviewed a number of various environment-responsive chemosensors
      related to fluorescent recognition of viscosity, polarity, temperature, hypoxia,
      and pH that have been reported thus far. 

PMID- 24723012
TI  - Physical activity for weight loss in children: is there any compensatory
      mechanism?
AB  - Although physical activity is primarily considered for its effects on energy
      expenditure for prevention and treatment of both overweight and obesity, its role
      in the regulation and control of energy balance seems more complex. Not only does
      physical activity affect energy expenditure, it also leads to modifications in
      energy intake and appetite that have been identified in children and that should
      be considered for weight loss. It also appears that it may not systematically
      favor increased energy expenditure due to individual differences in compensatory
      responses. This brief paper summarizes the pediatric evidence regarding those
      potential compensatory responses to physical activity and suggests that these
      compensatory responses of increasing physical activity levels may depend on
      children's adiposity status. 

PMID- 24723013
TI  - A carbon-coated TiO(2)(B) nanosheet composite for lithium ion batteries.
AB  - The carbon-coated TiO2(B) nanosheet composite synthesized by one-step hydrolysis
      of TiCl3 followed by vacuum annealing and air annealing delivers outstanding
      electrochemical performance as a negative electrode for Li-ion batteries, i.e.
      reversible capacity above 150 mA h g(-1) at 30 C (10 A g(-1)). 

PMID- 24723014
TI  - Biased reporting in surgery.

PMID- 24723015
TI  - Randomized multicentre trial of gadoxetic acid-enhanced MRI versus conventional
      MRI or CT in the staging of colorectal cancer liver metastases (Br J Surg 2014;
      101: 613-621).

PMID- 24723016
TI  - Long-term cost-effectiveness analysis of endovascular versus open repair for
      abdominal aortic aneurysm based on four randomized clinical trials (Br J Surg
      2014; 101: 623-631).

PMID- 24723017
TI  - Comparison of three ultrasound methods of measuring the diameter of the abdominal
      aorta.
AB  - BACKGROUND: Three ultrasound methods of measuring the diameter of the abdominal
      aorta exist: the outer-to-outer (OTO) method, where callipers are placed on the
      outer layer of the aortic wall; the inner-to-inner (ITI) method, where callipers
      are placed on the inner layer of the aortic wall; and the leading edge-to-leading
      edge (LELE) method, where callipers are placed on the outer layer of the anterior
      wall and the inner layer of the posterior wall. The aim was to determine the
      variability of the three methods, differences between them, and the consequences
      on prevalence estimates. METHODS: Some 127 consecutive patients with a small
      abdominal aortic aneurysm (AAA) were included. The maximal anteroposterior
      diameter was measured using the OTO, ITI and LELE methods by two vascular
      sonographers who were blinded to each other's measurements. The variability was
      described as the standard deviation. RESULTS: The variability was 2.7 (95 per
      cent limits of agreements +/- 5.4) mm for the OTO, 2.3 (+/- 4.6) mm for the ITI
      and 2.0 (+/- 4.0) mm for the LELE method. The corresponding coefficients of
      variability were 6.4, 6.1 and 5.0 per cent. The difference was 4.1 mm between ITI
      and OTO (P < 0.001), 2.0 mm between ITI and LELE (P < 0.001), and 2.1 mm between
      LELE and OTO (P < 0.001). CONCLUSION: LELE measurement was the most reproducible
      method of measuring the abdominal aorta. All methods showed a high degree of
      variability.

PMID- 24723018
TI  - National Vascular Registry Report on surgical outcomes and implications for
      vascular centres (Br J Surg 2014; 101: 637-642).

PMID- 24723019
TI  - Outcome of sleeve gastrectomy as a primary bariatric procedure.
AB  - BACKGROUND: Sleeve gastrectomy is being performed increasingly in Europe. Data on
      long-term outcome would be helpful in defining the role of sleeve gastrectomy.
      The aim of this study was to evaluate the outcome of sleeve gastrectomy as a
      primary bariatric procedure. METHODS: Medical charts of all patients who
      underwent a primary sleeve gastrectomy at the authors' institution between August
      2006 and December 2012 were reviewed retrospectively using a prospective online
      data registry. For evolution of weight loss and co-morbidity, only patients with
      follow-up of at least 1 year were included. A subgroup analysis was done to
      compare patients with an intended stand-alone procedure and those with an
      intended two-stage procedure. RESULTS: A total of 1041 primary sleeve
      gastrectomies were performed in the study period. Median duration of surgery was
      47 min, and median hospital stay was 2 days. Intra-abdominal bleeding occurred in
      27 patients (2.6 per cent) and staple-line leakage in 24 (2.3 per cent). Some 866
      patients had at least 1 year of follow-up. Mean excess weight loss was 68.4 per
      cent after 1 year (P < 0.001) and 67.4 per cent after 2 years. Smaller groups of
      patients achieved a mean excess weight loss of 69.3 per cent (163 patients), 70.5
      per cent (62) and 58.3 per cent (19) after 3, 4 and 5 years respectively. No
      difference in postoperative complications was found between the subgroups.
      Seventy-one (8.2 per cent) of 866 patients had a revision of the sleeve
      gastrectomy; reflux or dysphagia was the indication in 34 (48 per cent) of these
      patients. CONCLUSION: Sleeve gastrectomy is a safe and effective bariatric
      procedure. Maximum weight loss was achieved after 4 years. Long-term results
      regarding weight loss and co-morbidities were satisfactory.

PMID- 24723020
TI  - Outcome of sleeve gastrectomy as a primary bariatric procedure (Br J Surg 2014;
      101: 661-668).

PMID- 24723021
TI  - Radical versus conservative surgical treatment of liver hydatid cysts (Br J Surg
      2014; 101: 669-675).

PMID- 24723022
TI  - Impact of routine intraoperative cholangiography during laparoscopic
      cholecystectomy on bile duct injury (Br J Surg 2014; 101: 677-684).

PMID- 24723023
TI  - Preoperative nomogram to predict risk of bowel injury during adhesiolysis.
AB  - BACKGROUND: Inadvertent bowel injury during adhesiolysis is a major cause of
      increased morbidity and mortality following abdominal surgery. Identification of
      risk factors predicting this complication would guide preoperative counselling
      and surgical decision-making. The aim of this study was to identify predictive
      preoperative factors for inadvertent bowel injury occurring during adhesiolysis.
      METHODS: All patients undergoing elective abdominal surgery between June 2008 and
      June 2010 were evaluated prospectively as part of the LAPAD study. Data on
      adhesiolysis and inadvertent organ injury were gathered by direct observation
      during operation. Univariable logistic regression was used to investigate factors
      that increased the risk of inadvertent bowel injury. Independent predictors of
      bowel injury were identified using multivariable logistic regression and used to
      create a clinical nomogram. RESULTS: Of 715 patients eligible for analysis, 48
      (6.7 per cent) had inadvertent bowel injuries. In 42 patients the defect was
      detected during operation and in nine at a later time (3 patients had both).
      Bowel resection was required for almost two-thirds of the enterotomies. The
      number of previous laparotomies, anatomical site of the operation, presence of
      bowel fistula and laparotomy via a pre-existing median scar were independent
      predictors of bowel injury. A clinical scoring system was constructed using a
      nomogram incorporating these risk factors; this had a predictive discrimination,
      measured as the area under the receiver operating characteristic curve, of 0.85.
      CONCLUSION: A nomogram based on four independent factors predicted the risk of
      inadvertent bowel injury. REGISTRATION NUMBER: NCT01236625
      (http://www.clinicaltrials.gov).

PMID- 24723024
TI  - Authors' reply: Proximal margin length with transhiatal gastrectomy for Siewert
      type II and III adenocarcinomas of the oesophagogastric junction (Br J Surg 2013;
      100: 1050-1054).

PMID- 24723025
TI  - Proximal margin length with transhiatal gastrectomy for Siewert type II and III
      adenocarcinomas of the oesophagogastric junction (Br J Surg 2013; 100: 1050
      1054).

PMID- 24723026
TI  - Author's reply: Assessment of abdominoperineal resection rate as a surrogate
      marker of hospital quality in rectal cancer surgery (Br J Surg 2013; 100: 1655
      1663).

PMID- 24723027
TI  - Assessment of abdominoperineal resection rate as a surrogate marker of hospital
      quality in rectal cancer surgery (Br J Surg 2013; 100: 1655-1663).

PMID- 24723030
TI  - Expression of P2X3 and P2X 5 myenteric receptors varies during the intestinal
      postnatal development in the guinea pig.
AB  - P2X3 receptor expression in various tissues appears to be modulated by age. In
      the present study, we used single cell RT-PCR to determine the number of P2X3
      positive myenteric neurons at different stages of guinea pig postnatal
      development, and we tested if similar changes also occur to other myenteric P2X
      receptors. Moreover, we carried out whole-cell recordings using Patch Clamp
      techniques to determine possible changes in P2X receptors sensitivity to ATP and
      alpha,beta-methylene ATP (alpha,beta-meATP) between newborn and adult animals.
      Our data indicate that P2X3 subunit transcripts are present in a larger number of
      myenteric neurons from newborn guinea pigs whereas P2X5 mRNA is found more
      frequently in adults. Expression of P2X2 and P2X4 transcripts does not change
      during postnatal development. In newborn animals, virtually all neurons
      expressing P2X3 also expressed P2X2 transcripts. This is important because these
      two subunits are known to form heteromeric channels. ATP potency to activate P2X
      receptors in neurons of both newborn and adult animals was the same. alpha,beta
      meATP, a known P2X3 receptor agonist, induces only a marginal current despite the
      fact of the higher presence of P2X3 subunits in newborns. These findings imply
      that P2X3 subunits are mainly forming heteromeric, alpha,beta-meATP insensitive
      channels perhaps because P2X3 contributes with only one subunit to the
      heterotrimers while the other subunits could be P2X2, P2X4, or P2X5.

PMID- 24723031
TI  - Transcriptional expression of six genes located on pBSSB1 of Salmonella enterica
      serovar Typhi in different growth phases and environmental stresses.
AB  - A linear plasmid pBSSB1 of z66-positive Salmonella enterica serovar Typhi was
      previously identified to be involved in unidirectional flagellar phase variation
      due to the expression and regulation of fljB(z66) and fljA located on it.
      However, the expression of the remaining genes and other possible functions of
      pBSSB1 have not been reported yet. Here, we investigated the transcriptional
      expression characteristics of six genes (002, 008, 012, 017, 021, and 026)
      located on the linear plasmid pBSSB1 in different growth phases and environmental
      stresses by means of qRT-PCR. The results show that these six genes are all
      transcribed in normal growth condition (LB broth at 37  degrees C with stirring
      250 rpm), and their expression has an increasing trend in general with the growth
      of the bacteria. Under environmental stresses, there is an increase in expression
      levels of 002, 008, 012, and 026, while no significant change in expression was
      observed for 017 and 021. In addition, the expression levels and modes of 017 and
      021 are similar in all the growth conditions. To our knowledge, this is the first
      report describing the transcriptional expression characteristics of these six
      genes located on pBSSB1 and suggesting that pBSSB1 may be very important in
      response to the environmental stresses in z66-positive S. enterica serovar Typhi.

PMID- 24723032
TI  - Eye movements of university students with and without reading difficulties during
      naming speed tasks.
AB  - Although naming speed (NS) has been shown to predict reading into adulthood and
      differentiate between adult dyslexics and controls, the question remains why NS
      is related to reading. To address this question, eye movement methodology was
      combined with three letter NS tasks (the original letter NS task by Denckla &
      Rudel, Cortex 10:186-202, 1974, and two more developed by Compton, The Journal of
      Special Education 37:81-94, 2003, with increased phonological or visual
      similarity of the letters). Twenty undergraduate students with reading
      difficulties (RD) and 27 without (NRD) were tested on letter NS tasks (eye
      movements were recorded during the NS tasks), phonological processing, and
      reading fluency. The results indicated first that the RD group was slower than
      the NRD group on all NS tasks with no differences between the NS tasks. In
      addition, the NRD group had shorter fixation durations, longer saccades, and
      fewer saccades and fixations than the RD group. Fixation duration and fixation
      count were significant predictors of reading fluency even after controlling for
      phonological processing measures. Taken together, these findings suggest that the
      NS-reading relationship is due to two factors: less able readers require more
      time to acquire stimulus information during fixation and they make more saccades.

PMID- 24723033
TI  - Functional conservation of the glycosyltransferase gene GT47A in the monocot
      rice.
AB  - Glucuronoarabinoxylan is the major hemicellulose in grass cell walls, yet the
      mechanism of xylan synthesis in monocot plants is still unclear. Unraveling the
      genes involved in the biosynthesis of xylan in rice will be very important for
      the utilization of rice straw as a source of bioenergy in the future. In this
      report, we investigated the functional role of a rice gene homologous to
      Arabidopsis IRREGULAR XYLEM10 (IRX10), belonging to the glycosyl transferase (GT)
      gene family 47 (GT47), in the biosynthesis of xylan. The protein sequence of
      OsGT47A from rice exhibits a 93.49% similarity to IRX10, which is involved in the
      biosynthesis of glucuronoxylan in Arabidopsis. Phylogenetic analysis of the GT47
      glycosyl transferase family in the rice genome revealed that OsGT47A is a closely
      related homolog of IRX10 and IRX10L. Expression pattern analysis showed that the
      OsGT47A gene is highly expressed in the rice stem. Overexpression of OsGT47A in
      the irx10 irx10L double mutant rescued the plant growth phenotype and restored
      secondary wall thickness. Analysis of monosaccharides indicated that the rescued
      plants had levels of xylose identical to those of the wild type plants, and the
      fluorescence signals were restored in the complementation plants by xylan
      immunolocalization. The OsGT47A complementation under the native promoter of
      Arabidopsis IRX10L (ProIRX10L) partially rescued the double mutant, indicating
      that OsGT47A is functionally equivalent to IRX10L. Together, these results
      suggest that the IRX10 homolog OsGT47A exhibits functional conservation and is
      most likely involved in xylan synthesis in rice.

PMID- 24723035
TI  - Health reform and physician-led accountable care: the paradox of primary care
      physician leadership.

PMID- 24723034
TI  - An anterograde rabies virus vector for high-resolution large-scale reconstruction
      of 3D neuron morphology.
AB  - Glycoprotein-deleted rabies virus (RABV ?G) is a powerful tool for the analysis
      of neural circuits. Here, we demonstrate the utility of an anterograde RABV ?G
      variant for novel neuroanatomical approaches involving either bulk or sparse
      neuronal populations. This technology exploits the unique features of RABV ?G
      vectors, namely autonomous, rapid high-level expression of transgenes, and
      limited cytotoxicity. Our vector permits the unambiguous long-range and fine
      scale tracing of the entire axonal arbor of individual neurons throughout the
      brain. Notably, this level of labeling can be achieved following infection with a
      single viral particle. The vector is effective over a range of ages (>14 months)
      aiding the studies of neurodegenerative disorders or aging, and infects numerous
      cell types in all brain regions tested. Lastly, it can also be readily combined
      with retrograde RABV ?G variants. Together with other modern technologies, this
      tool provides new possibilities for the investigation of the anatomy and
      physiology of neural circuits.

PMID- 24723037
TI  - [40 years in-patient suicide research of the working group "Suicidality and the
      psychiatric hospital"].
AB  - OBJECTIVE: To give an retrospective overview according to the so-called in
      patient suicide especially in German psychiatric hospitals. METHOD: Summary of
      results of the working group "Suicidality and the psychiatric hospital" during
      the last four decades in Germany. RESULTS: First, it could be shown that there
      was a real increase of in-patient suicides during the 70(th) and 80(th) years.
      Two other results are important 1) an impressive decrease of suicide rates in the
      two last decades and 2) the observation of a change from the new high-risk group
      "young schizophrenic patients" back to the traditional suicide risk group of
      depressed patients.

PMID- 24723038
TI  - [Implementing Recovery-Orientation in Psychoeducation - An Attempt].
AB  - OBJECTIVE: This article explores the diverging implementation of the main
      principles of recovery in two group settings similar to psychoeducation. METHOD:
      Both groups were qualitatively examined, using participant observation, and
      compared to each other afterwards. RESULTS: Both groups used various models of
      disease, whereby the participants' subjective experiences were favoured. Kinds of
      interaction and communication among participants were dependent on spatial
      characteristics of both group settings. Various types of knowledge were employed,
      structuring the relations among participants. CONCLUSIONS: More standardized
      modes of transferring knowledge, often utilized in psychoducational settings, are
      less compatible with such an approach.

PMID- 24723039
TI  - [Involuntary admissions in accordance to the Mental Health Act (PsychKG) - what
      are the strongest predictors?].
AB  - OBJECTIVE: Involuntary psychiatric admissions under the Mental Health Act
      increased significantly nationwide. Little is known, however, about the
      influencing factors of this phenomenon. METHODS: The aim of this regional cross
      sectional study in North Rhine-Westphalia was to compare voluntary and
      involuntary psychiatric admissions (under the PsychKG NRW) regarding personal,
      institutional, social-psychiatric and demographic characteristics. A
      retrospective analysis of hospital admission registers over a period of 6 years
      with over 200 000 cases was conducted. RESULTS: Elderly patients with dementia
      were most frequently involuntarily admitted. The existence of a locked ward in
      hospitals did not per se increase involuntary admissions, whereas the scope and
      quality of local social-psychiatric services had a major impact. CONCLUSION:
      Social-psychiatric services and home-treatment must be strengthened to achieve
      lower involuntary admission rates and to further improve the quality of mental
      health care all over Germany.

PMID- 24723040
TI  - [High utilisers with affective and schizophrenic disorders in the psychiatric
      health care system: a comparison between Eastern and Western Germany].
AB  - OBJECTIVE: High utilisers of psychiatric services are defined as a group of
      patients showing a great amount of service use, especially inpatient care,
      consequently causing immense costs. There is a lack of studies investigating
      differences between East and West Germany. METHODS: Service use and
      psychopathology were examined in 350 high utilisers receiving inpatient treatment
      in one East German and three West German psychiatric hospitals. RESULTS: Whereas
      current length of stay was higher in participants from West Germany, readmissions
      were more frequent in the East German participants who also exhibited higher
      psychopathology. CONCLUSION: Presumably, the deficient situation of outpatient
      health care in East Germany is compensated by increased stationary admission,
      consequently leading to a structural promotion of high utilisation.

PMID- 24723041
TI  - [Dialectical Behavior Therapy (DBT)--developments and empirical evidence].
AB  - OBJECTIVE: Dialectical Behavior Therapy has been initially designed and evaluated
      as an outpatient-treatment program for chronic suicidal female patients. Within
      the last years, several adaptations of DBT for specific comorbidities, other
      settings or other disorders related to emotion dysregulation have been developed.
      This report reviews conceptual aspects and the scientific evidence of initially
      designed Dialectical Behavior Therapy and the adaptations. METHODS: Systematic
      literature search and systematic review. RESULTS: Recently, two meta-analyses
      which are based on randomized controlled trials conclude robust and stabile
      effects of DBT Evidence from further RCTs and other studies show promise for the
      properties of many DBT adaptations. CONCLUSION: The current review of the
      literature suggests a good effectiveness of DBT, especially on complex disorders
      with deficits in the field of emotion regulation.

PMID- 24723042
TI  - A longitudinal perspective on childhood adversities and onset risk of various
      psychiatric disorders.
AB  - It is well-known that childhood adversities can have long-term effects on mental
      health, but a lot remains to be learned about the risk they bring about for a
      first onset of various psychiatric disorders, and how this risk develops over
      time. In the present study, which was based on a Dutch longitudinal population
      survey of adolescents TRAILS (N = 1,584), we investigated whether and how
      childhood adversities, as assessed with three different measures, affected the
      risk of developing an incident depressive, anxiety, or disruptive behavior in
      childhood and adolescence. In addition, we tested gender differences in any of
      the effects under study. The results indicated that depressive, anxiety and
      disruptive behavior disorders each had their own, characteristic, pattern of
      associations with childhood adversities across childhood and adolescence, which
      was maintained after adjustment for comorbid disorders. For depressive disorders,
      the overall pattern suggested a high excess risk of incidence during childhood,
      which decreased during adolescence. Anxiety disorders were characterized by a
      moderately increased incident risk during childhood, which remained approximately
      stable over time. Disruptive behavior disorders took an intermediate position. Of
      the three childhood adversities tested, an overall rating of the stressfulness of
      the childhood appeared to predict onset of psychiatric disorders best. To
      conclude, the risk of developing a psychiatric disorder after exposure to
      adversities early in life depends on the nature of the adversities, the nature of
      the outcome, and the time that has passed since the adversities without disorder
      onset. 

PMID- 24723043
TI  - alpha-Klotho mice demonstrate increased expression of the non-sulfated N-glycan
      form of the HNK-1 glyco-epitope in kidney tissue.
AB  - The alpha-Klotho mouse is an animal model that prematurely exhibits phenotypes
      resembling human aging owing to mutation of the alpha-Klotho gene. Although alpha
      Klotho mice appear normal at birth, they begin showing multiple age-associated
      disorders after 3-4 weeks. Meanwhile, overexpression of alpha-Klotho extends
      lifespan. Therefore, alpha-Klotho may be involved in the aging process. The alpha
      Klotho protein has homology to beta-glucosidase and is proposed to have
      glycosidase activity. However, it is unclear whether glycan alterations are
      present in alpha-Klotho mice. Here we found increased levels of the non-sulfated
      HNK-1 glyco-epitope in the kidneys of alpha-Klotho mice. This phenomenon was also
      observed in normal aged mice. Immunohistochemical analysis demonstrated that
      increased non-sulfated HNK-1 glyco-epitope appeared predominantly in the outer
      half of the renal cortex, where alpha-Klotho protein is highly expressed. To
      clarify the cause, the expression of glucuronyltransferase S (GlcAT-S) and the
      activity of beta-glucuronidase were also examined. The expressions of GlcAT-S
      were comparable in alpha-Klotho mice and wild-type mice, but beta-glucuronidase
      activity was lower in alpha-Klotho mice than in wild-type. These results suggest
      that increased non-sulfated HNK-1 epitope levels in alpha-Klotho mice may be due
      to decreased beta-glucuronidase activity. Taken together, alpha-Klotho expression
      was associated with expression of the non-sulfated HNK-1 epitope. 

PMID- 24723044
TI  - The impact of modified tongue base suspension on CPAP levels in patients with
      severe OSA.
AB  - The aim of this study was to evaluate the effects of modified tongue base
      suspension (mTBS) procedure on continuous positive airway pressure (CPAP) levels
      in patients with severe obstructive sleep apnea (OSA). From November 2011 to
      December 2012, a total of 31 patients with severe OSA who underwent mTBS were
      included into this prospective case series with planned data collection. Prior to
      surgery, all the patients were subjected to a polysomnography (PSG) and CPAP
      titration on two separate nights. Following the surgery, patients were subjected
      to a control PSG and CPAP titration at the sixth month of follow-up period. The
      preoperative and postoperative mean apnea hypopnea index (AHI), CPAP titration
      values, AHI during CPAP use and amount of sleeping time with CPAP were compared.
      Median age was 48 years (range 31-66), and most patients were male (87.0 %).
      Postoperative mean AHI (44.73 +/- 17.05 vs. 19.96 +/- 19.52), optimal CPAP value
      (12.64 +/- 1.60 vs. 8.00 +/- 1.77) and AHI during CPAP use (3.79 +/- 1.78 vs.
      2.25 +/- 1.81) were decreased, and the amount of sleeping time with CPAP (5.29 +/
      0.84 vs. 6.52 +/- 0.89) was increased significantly (p < 0.001 for all
      parameters). The surgery was considered to be successful when 50 % reduction in
      the mean AHI and/or the decrease of AHI below 20/h were obtained. A total of 24
      patients (77.4 %) met the surgical success criteria. The mTBS is a safe and
      feasible procedure with favorable effects on CPAP levels in patients with severe
      OSA. 

PMID- 24723045
TI  - Pingyangmycin as first-line treatment for low-flow orbital or periorbital venous
      malformations: evaluation of 33 consecutive patients.
AB  - IMPORTANCE: Low-flow orbital or periorbital venous malformation (OVM) is the most
      common periorbital vascular lesion that may produce an appearance defect, visual
      dysfunction, internal hemorrhage, and thrombosis. Intralesional injection of
      pingyangmycin as a minimally invasive, gentle intervention may have better
      outcomes in treating low-flow OVMs compared with other currently used methods.
      OBJECTIVE: To investigate the efficacy and safety of intralesional injection of
      pingyangmycin for treatment of low-flow OVM. DESIGN, SETTING, AND PARTICIPANTS: A
      retrospective, noncomparative, interventional case series was conducted in a
      single medical center. Thirty-three consecutive patients with low-flow OVMs
      undergoing intralesional injection of pingyangmycin were included in the study.
      INTERVENTIONS: Injections of 1 to 5 mL of a pingyangmycin 1.5-mg/mL mixture with
      lidocaine hydrochloride, 2%, were given. Each patient received 1 to 4 injections
      at an interval of 6 to 8 weeks between February 2002 and January 2013. Mixture
      volume was determined on a basis of 0.5 mL of solution per cubic centimeter of
      the lesion. The maximum dose for 1 injection was 8 mg. Clinical observations were
      well documented before and after treatment. MAIN OUTCOMES AND MEASURES: Reduction
      of lesion volume based on ultrasound-measured volume; overall appearance,
      including blue color and thickness of lesions before and after treatment; and
      adverse events were evaluated. RESULTS: Patients received a median of 2 (range, 1
      4) intralesional injections of pingyangmycin. The mean pretreatment volume was
      4.4 cm3 and posttreatment volume was 1.0 cm3 (t = 4.63; P < .001), with a mean
      decrease of 84% (range, 28%-100%). Marked to moderate improvement in the volume
      of the lesions was noticed in 31 eyes (94%; 25 of 33 [76%] with marked
      improvement and 6 of 33 [18%] with moderate improvement). Improvement occurred in
      95% (18 of 19) of superficial lesions, 100% (3 of 3) of deep lesions, and 91% (10
      of 11) of combined lesions. We noticed significant improvements in blue color and
      thickness on the basis of investigator scores from clinical photographs taken
      before and after treatment. None of the patients had recurrence noted at their
      final follow-up. Adverse events were limited to swelling of the conjunctiva and
      localized subcutaneous atrophy. CONCLUSIONS AND RELEVANCE: The results of
      intralesional pingyangmycin injection for treatment of low-flow OVM are
      encouraging and associated with a low risk of adverse events.

PMID- 24723046
TI  - Altered insulin response to an acute bout of exercise in pediatric obesity.
AB  - Pediatric obesity typically induces insulin resistance, often later evolving into
      type 2 diabetes. While exercise, enhancing insulin sensitivity, is broadly used
      to prevent this transition, it is unknown whether alterations in the exercise
      insulin response pattern occur in obese children. Therefore, we measured exercise
      insulin responses in 57 healthy weight (NW), 20 overweight (OW), and 56 obese
      (Ob) children. Blood samples were drawn before and after 30 min of intermittent
      (2 min on, 1 min off) cycling at ~80% VO2max. In a smaller group (14 NW, 6 OW, 15
      Ob), a high-fat meal was ingested 45 min preexercise. Baseline glycemia was
      similar and increased slightly and similarly in all groups during exercise. Basal
      insulin (pmol/L) was significantly higher in Ob vs. other groups; postexercise,
      insulin increased in NW (+7+/- 3) and OW (+5 +/- 8), but decreased in Ob (-15+/
      5, p < .0167 vs. NW). This insulin drop in Ob was disproportionately more
      pronounced in the half of Ob children with higher basal insulin (Ob-H). In all
      groups, high-fat feeding caused a rapid rise in insulin, promptly corrected by
      exercise. In Ob, however, insulin rose again 30 min postexercise. Our data
      indicates a distinct pattern of exercise-induced insulin modulation in pediatric
      obesity, possibly modulated by basal insulin concentrations.

PMID- 24723047
TI  - Special issue introduction: Thriving across the adolescent years: a view of the
      issues.
AB  - Framed within a relational developmental systems model, the 4-H Study of positive
      youth development (PYD) explored the bases and implications of thriving across
      much of the second decade of life. This special issue pertains to information
      derived from the recently completed eight waves of the 4-H Study of PYD, and
      presents findings about the relations between individual and contextual variables
      that are involved in the thriving process. This introduction briefly reviews the
      historical background and the theoretical frame for the 4-H Study and describes
      its general methodology. We provide an overview of the articles in this special
      issue and discuss the ways in which the articles elucidate different facets of
      the thriving process. In addition, we discuss the implications of this research
      for future scholarship and for applications aimed at improving the life chances
      of diverse adolescents. 

PMID- 24723048
TI  - Invited commentary: Resilience and positive youth development frameworks in
      developmental science.
AB  - Positive youth development (PYD) and resilience science differ in emphasis and
      focus but share many roots, assumptions, concepts, and goals. Both frameworks are
      grounded in developmental systems theory, both are focused on positive
      adaptation, and both are translational, sharing a common goal of promoting
      positive development. Yet there also are differences. This commentary examines
      the concepts, methods, and goals that define the PYD framework as embodied by the
      4-H Study of PYD from the perspective of contemporary resilience science in human
      development, with an eye toward delineating similarities, differences, and future
      directions. 

PMID- 24723049
TI  - Invited commentary: Improving the human condition through rigorous, applied
      developmental research.
AB  - This invited commentary describes the shifts toward a more positive
      characterization of young people over the past 30 years. After describing the new
      focus on the strengths of young people and the need to ground our understanding
      in developmental science, it provides an overview of the major contributions of
      this special issue to the field of positive youth development. Taken together,
      the groundbreaking work on the 4-H study demonstrates the increasing
      methodological and statistical sophistication of this strength-based approach. 

PMID- 24723050
TI  - Invited commentary: Exploring the promises, intricacies, and challenges to
      positive youth development.
AB  - We highlight the need for and critical importance of the program of research
      reported in this Special Issue. We emphasize that a focus on positive youth
      development is sorely overdue. The impressive project covering one decade, 42
      states and 7,000 participants demonstrates critical contributors to positive
      youth development. The two identified themes emerging from the set of papers are
      that contexts and the nature of assets matter for youth. Collectively, the papers
      explored a variety of positive youth development relevant questions and utilized
      combinations of annual assessments and data sources from an extraordinary data
      base. The core methodological and conceptual flaw across papers was the under
      representation of minorities in the data set, which limited the generalizability
      of findings. While the major shortcoming was acknowledged at the onset and
      recognized as a failing in each paper, nevertheless, merely conceding the flaw
      was seen as insufficient given the policy, practice, and research implications.
      The inadequate sampling and follow-up of youth from families which continue to
      face persistent social inequality and having the most to gain from a positive
      youth development conceptual strategy and was a major shortcoming; it prevented
      within group analyses. The co-authors note that although research decisions made
      limited the generalizability of the positive youth development research strategy
      for non-white American youth, the intended goals for inclusiveness are evident
      and, accordingly, suggest a level of hopefulness. 

PMID- 24723051
TI  - Peer influence and context: the interdependence of friendship groups, schoolmates
      and network density in predicting substance use.
AB  - This article focuses on the degree to which friends' influence on substance use
      is conditioned by the consistency between their behavior and that of schoolmates
      (individuals enrolled in the same school, but not identified as friends),
      contributing to the literature on the complexity of interactive social influences
      during adolescence. Specifically, it hypothesizes that friends' influence will
      diminish as their norms become less similar to that of schoolmates. The authors
      also propose that this conditioning relationship is related to the density of the
      friendship group. This study uses data from the National Longitudinal Survey of
      Adolescent Health (AddHealth) (n ~ 8,000, 55% female) to examine the interactive
      relationship between friend and schoolmate influences on adolescent substance use
      (smoking and drinking). The sample contains students ranging from age 11 to 22
      and is 60% White. The findings demonstrate that, as the substance use of the
      friendship group becomes more dissimilar from schoolmates' substance use, the
      friendship group's influence on adolescent substance use diminishes. Further, the
      results demonstrate that this conditioning relationship does not emerge when the
      friendship group is highly dense.

PMID- 24723052
TI  - Subversion of early innate antiviral responses during antibody-dependent
      enhancement of Dengue virus infection induces severe disease in immunocompetent
      mice.
AB  - Dengue is a mosquito-borne disease caused by one of four serotypes of Dengue
      virus (DENV-1-4). Epidemiologic and observational studies demonstrate that the
      majority of severe dengue cases, dengue hemorrhagic fever and dengue shock
      syndrome (DHF/DSS), occurs predominantly in either individuals with cross
      reactive immunity following a secondary heterologous infection or in infants with
      primary DENV infections born from dengue-immune mothers, suggesting that B-cell
      mediated and antibody responses impact on disease evolution. We demonstrate here
      that B cells play a pivotal role in host responses against primary DENV infection
      in mice. After infection, MUMT(-/-) mice showed increased viral loads followed by
      severe disease manifestation characterized by intense thrombocytopenia,
      hemoconcentration, cytokine production and massive liver damage that culminated
      in death. In addition, we show that poly and monoclonal anti-DENV-specific
      antibodies can sufficiently increase viral replication through a suppression of
      early innate antiviral responses and enhance disease manifestation, so that a
      mostly non-lethal illness becomes a fatal disease resembling human DHF/DSS.
      Finally, treatment with intravenous immunoglobulin containing anti-DENV
      antibodies confirmed the potential enhancing capacity of subneutralizing
      antibodies to mediate virus infection and replication and induce severe disease
      manifestation of DENV-infected mice. Thus, our results show that humoral
      responses unleashed during DENV infections can exert protective or pathological
      outcomes and provide insight into the pathogenesis of this important human
      pathogen. 

PMID- 24723053
TI  - Fluconazole prophylaxis is associated with a decreased rate of coagulase-negative
      Staphylococcal infections in a subset of extremely low birth weight neonates.
AB  - Fluconazole prophylaxis is being used efficaciously in the neonatal intensive
      care unit (NICU) for fungal prophylaxis in very low birth weight and extremely
      low birth weight (ELBW) neonates. Little is known about the effect of fluconazole
      prophylaxis on bacterial infections. The purpose of this study was to examine
      that issue in a subset of ELBW, those weighing <=900 g at birth. This is a
      retrospective study conducted in a level III NICU at state-designated children
      hospital in New Jersey (USA). We examined the data from our records of neonates
      <= 900 g birth weight during the period March 1, 2007-February 28, 2011.
      Inclusion in the study was all infants <= 900 g before (n = 67) and after (n =
      81) the institution of fluconazole prophylaxis. Fluconazole prophylaxis was
      accompanied by a significant decrease in both the rate and number of days of
      bacterial infections as well as co-infections. We found that the incidence of
      coagulase-negative Staphylococcus (CONS) decreased from 46.2 to 24.7 % (OR 2.63;
      95 % CI 1.31-5.27). Similarly, days of infection also decreased significantly (p
      < 0.0001). These data suggest that fluconazole prophylaxis may be associated with
      a reduction in CONS infections in that subset of ELBW neonates.

PMID- 24723054
TI  - Intravenous administration of a single-dose free-circulating DNA of colitic
      origin improves severe murine DSS-colitis.
AB  - In inflammatory bowel diseases the presence of free-circulating DNA (fcDNA)
      sequences in the sera is an established phenomenon, albeit its real biological
      function still remains unclear. In our study the immunobiologic effects of a
      single-dose, intravenously administered fcDNA of normal and colitic origin were
      assayed in DSS-colitic and control mice. In parallel with disease and
      histological activity evaluations changes of the TLR9 and inflammatory cytokine
      signaling gene expression profiles were assayed in isolated cells of the lamina
      propria. Intravenously administered colitis-derived fcDNA displayed a more
      prominent beneficial action regarding the clinical and histological severity of
      DSS-colitis than that of fcDNA of normal origin. Systemic administration of
      colitis-derived fcDNA significantly altered the expression of certain TLR9
      related and proinflammatory cytokine genes in a clinically favorable manner.
      Presumably due to induction of severe colitis, the subsequent marked inflammatory
      environment may result changes in fcDNA with a potential to promote the
      downregulation of inflammation and improvement of tissue regeneration.
      Elucidating mechanisms of innate immune alterations by nucleic acids may provide
      further insight into the etiology of inflammatory bowel diseases, and develop the
      basis of novel nucleic acid-based immunotherapies.

PMID- 24723056
TI  - Cardiomyocyte-like cells differentiation from non beta-catenin expression
      mesenchymal stem cells.
AB  - Recent studies have shown that block wnt/beta-catenin signaling pathway is
      integrant for cardiomyocytes differentiation from bone marrow mesenchymal stem
      cells (MSCs). By transducing the MSCs with lentivirus which contain beta-catenin
      interference RNA, we screened out the non beta-catenin expression clone. In the
      establishment of knockdown beta-catenin in MSCs, we investigated the role of 5
      azacytidine (5-aza), salvianolic acid B (salB), and cardiomyocytes lysis medium
      (CLM) in inducing MSCs to differentiate into cardiomyocyte-like cells. A method
      for culturing MSCs and cardiomyocytes was established. Purified MSCs were
      investigated by flow cytometry. The MSCs were positive for CD90 and CD29, but
      negative for CD34 and CD45. Meanwhile, the cardiomyocytes contracted
      spontaneously after 24 h of seeding into the plates. The fourth-passage non-beta
      catenin expression MSCs were divided into eight groups: control group, 5-aza,
      salB, CLM, 5-aza + salB, 5-aza + CLM, salB + CLM, and 5-aza + salB + CLM. The
      gene and protein expression of cTnT, alpha-actin, beta-myosin, beta-catenin, and
      GSK-3beta were detected by quantitative real-time PCR and Western blotting. Our
      results showed that cTnT expression in 5-aza + salB + CLM group was ninefold
      higher than in the control group in the non-beta-catenin MSCs model, implying
      that cardiomyocytes differentiation from MSCs is an extremely complicated process
      and it is necessary to consider the internal and external environmental
      conditions, such as suitable pharmaceutical inducers, cardiomyocytes
      microenvironments, inhibition of the negative signaling pathway and so on. 

PMID- 24723057
TI  - Surprising acidity of hydrated lithium cations in organic solvents.
AB  - Lithium cations are shown to have a significant role in catalyzing oxygen and
      proton reduction along with S(N)1 reactions in biphasic systems. We propose that
      this catalytic effect is due to the surprising acidity of the hydrated cations;
      interactions between the cation and its surrounding solvation shell will make the
      constituent water molecules more acidic.

PMID- 24723055
TI  - Fatty acid effect on sucrose-induced enamel demineralization and cariogenicity of
      an experimental biofilm-caries model.
AB  - Based on scarce evidence, fatty acids have been described as anticariogenic. The
      aim was to evaluate the effect of different types of fatty acids on enamel
      demineralization and on the cariogenic properties of Streptococcus mutans
      biofilms on a biofilm/caries model. Mature biofilms of S. mutans UA159 growing on
      bovine enamel slabs were exposed to 10% sucrose for 5 min, 3 times per day
      followed by exposure to a panel of free fatty acids, including monounsaturated
      (oleic), polyunsaturated (linoleic) and saturated (stearic) fatty acids, in
      concentrations of 0.1, 1 and 10 mM for five additional minutes. Enamel
      demineralization was determined before and after the experiments by
      microhardness. Slabs were retrieved to analyze biofilm biomass, viable bacterial
      counts and polysaccharide production. Biofilms exposed to sucrose, followed by
      oleic and linoleic acids, showed less demineralization than sucrose alone (p <
      0.05). Biomass, S. mutans colonies and insoluble extracellular polysaccharide
      production were reduced from the biofilms treated with oleic and linoleic fatty
      acids (p < 0.05). No differences with the positive control were observed with the
      saturated stearic acid. Poly and monounsaturated fatty acids presented to S.
      mutans biofilms after a cariogenic challenge appear to reduce demineralization on
      enamel and to interfere with cariogenicity of S. mutans biofilms.

PMID- 24723058
TI  - [Influence of anterior cruciate reconstruction on postural stability: A pre- and
      postoperative comparison].
AB  - BACKGROUND: Ruptures of the anterior cruciate ligament (ACL) lead to an
      anteromedial rotational instability in the knee joint and, thus, to a
      deterioration of the patient's ability to stand (postural control). It still
      remains unclear whether postural control can be restored by ACL reconstruction.
      The aim of this study was to investigate the effect of a unilateral ACL graft on
      the ability to stably stand on the injured leg using computer-aided dynamic
      posturography (CDP); the stability indices on standing on one leg were compared
      pre- and postoperatively. PATIENTS AND METHODS: A total of 25 patients were
      studied after unilateral ACL injury and subsequent ACL reconstruction using CDP.
      The average time of follow-up was 608 days (range 357-821 days). The ability to
      stably stand on the healthy and injured leg was compared and evaluated for
      significant differences. RESULTS: There was a significant improvement of postural
      control after ACL reconstruction. The Overall Stability Index (OSI) for the leg
      with ACL rupture was 3.7 degrees  +/- 1.6 degrees  preoperatively and 3.0 degrees
      +/- 1.1 degrees  postoperatively (p < 0.05). In the postoperative comparison
      with the healthy leg, the value in the operated leg was 3.0 degrees  +/- 1.1
      degrees  and the healthy leg was 3.0 degrees  +/- 1.4 degrees  (p = 0.99).
      CONCLUSIONS: ACL replacement can be improve stability compared to the
      preoperative value by about 21% and even the stability level of the contralateral
      healthy knee can be achieved.

PMID- 24723059
TI  - [Challenges in the context of medical care during a naval research expedition. A
      case report].
AB  - Exploration for natural resources in the seabed of the Indian Ocean was
      undertaken by the German government institution of earth sciences and resources
      ("Bundesanstalt fur Geowissenschaften und Rohstoffe", BGR) in November 2012. To
      provide for the medical safety of crew and scientists, a cooperation between the
      BGR and the trauma department of the Hannover Medical School was established.
      Research by physicians accompanying the naval expedition revealed that medical
      consultations mainly occur because of respiratory infections, abdominal
      discomfort, genitourinary discomfort and seasickness, with the rate of traumas
      being between 31% and 41%. Di Giovanna et al. stated that 97% of all emergencies
      on cruise ships are not critical and only 3% need an immediate emergency medical
      intervention. Consultations were already performed on the mainland prior to
      departure and included minor traumas due to non-appropriate footwear, otitis and
      respiratory infections. Seasickness was the main reason for consultation during
      the first days at sea. Strong seas resulted in some bruises. Minor injuries and
      foreign body injuries to the hands and feet also required consultation. First
      degree sunburns resulted from exposure to the sun, while air-conditioning caused
      rhinosinusitis and conjunctivitis. A special consultation was a buccal splitting
      of tooth 36. An immediate emergency medical intervention was not necessary due to
      the relative low level of pain for the patient; however, due to the risk of
      further damage caused by nocturnal bruxism, a protective splint was formed using
      a small syringe. Other reasons for consultation were similar to those reported in
      the general literature. Medical activities at exotic locations may create the
      vision of a holiday character at first; however, intensive planning and
      preparation are needed. We recommend contacting police, customs, the federal
      institute for drugs and medical devices as well as the labour inspectorate,
      preferably in both the originating country and the destination, to prepare custom
      formalities and to obtain formal documents and approvals beforehand. It is
      advisable to be prepared not only for emergency situations, but also for general
      medical and dental problems. Improvisation in the treatment of special health
      problems is an unavoidable requisite.

PMID- 24723060
TI  - [Treatment of tibial pseudoarthrosis. Complications after intramedullary,
      allogeneic fibular grafting].
AB  - A 24-year-old woman underwent cosmetic bilateral tibial lengthening with severe
      complications. In all, 15 operations, including allogeneic fibular grafting of
      both tibia, were required to treat unstable bilateral non-union, malalignment,
      and osteomyelitis of the right tibia.The present article describes the surgical
      strategy of revision to achieve good recovery with full consolidation and proper
      alignment of the lower leg. Furthermore, the indications for allogeneic bone
      grafting, which was described by Erich Lexer 100 years ago, are discussed. For
      surgical revision, a T-external fixator was used on the right leg, while a
      customized tibial nail was used on the left leg. Using these techniques, full
      consolidation and proper alignment was achieved. Allogeneic bone grafts in upper
      extremity defects cannot be recommended.

PMID- 24723061
TI  - Anti-cancer palladium complexes: a focus on PdX2L2, palladacycles and related
      complexes.
AB  - Much success has been achieved with platinum-based chemotherapeutic agents, i.e.
      through interactions with DNA. The long-term application of Pt complexes is
      thwarted by issues, leading scientists to examine other metals such as palladium
      which could exhibit complementary modes of action (given emphasis wherever
      known). Over the last 10 years several research groups have focused on the
      application of an eclectic array of palladium complexes (of the type PdX2L2,
      palladacycles and related structures) as potential anti-cancer agents. This
      review therefore provides readers with an up to date account of the advances that
      have taken place over the past several decades. 

PMID- 24723063
TI  - [Rehabilitation and need for care].

PMID- 24723064
TI  - [Are mental disorders increasing?].

PMID- 24723065
TI  - [E-health: trends in rehabilitation and psychotherapy - expert meeting of the
      university medical center, November 23, 2013 in Mainz].

PMID- 24723068
TI  - Lie Markov models with purine/pyrimidine symmetry.
AB  - Continuous-time Markov chains are a standard tool in phylogenetic inference. If
      homogeneity is assumed, the chain is formulated by specifying time-independent
      rates of substitutions between states in the chain. In applications, there are
      usually extra constraints on the rates, depending on the situation. If a model is
      formulated in this way, it is possible to generalise it and allow for an
      inhomogeneous process, with time-dependent rates satisfying the same constraints.
      It is then useful to require that, under some time restrictions, there exists a
      homogeneous average of this inhomogeneous process within the same model. This
      leads to the definition of "Lie Markov models" which, as we will show, are
      precisely the class of models where such an average exists. These models form Lie
      algebras and hence concepts from Lie group theory are central to their
      derivation. In this paper, we concentrate on applications to phylogenetics and
      nucleotide evolution, and derive the complete hierarchy of Lie Markov models that
      respect the grouping of nucleotides into purines and pyrimidines-that is, models
      with purine/pyrimidine symmetry. We also discuss how to handle the subtleties of
      applying Lie group methods, most naturally defined over the complex field, to the
      stochastic case of a Markov process, where parameter values are restricted to be
      real and positive. In particular, we explore the geometric embedding of the cone
      of stochastic rate matrices within the ambient space of the associated complex
      Lie algebra. 

PMID- 24723067
TI  - A center's experience: pulmonary function in spinal cord injury.
AB  - Traumatic spinal cord injury (SCI) is associated with significant psychological
      and physical challenges. A multidisciplinary approach to management is essential
      to ensure recovery during the acute phase, and comprehensive rehabilitative
      strategies are necessary to foster independence and quality of life throughout
      the chronic phase of injury. Complications that beset these individuals are often
      a unique consequence of SCI, and knowledge of the effects of SCI upon organ
      systems is essential for appropriate management. According to the National SCI
      Statistical Center (NSCISC), as of 2010 there were an estimated 265,000 persons
      living with SCI in the United States, with approximately 12,000 incidence cases
      annually. Although life expectancy for newly injured individuals with SCI is
      markedly reduced, persons with chronic SCI are expected to live about as long as
      individuals without SCI; however, longevity varies inversely with level of
      injury. Since 2005, 56 % of persons with SCI are tetraplegic, and due to
      paralysis of respiratory muscles, these individuals may be especially prone to
      pulmonary complications, which remain a major cause of mortality among persons
      with chronic SCI. We at the VA Rehabilitation Research and Development Center of
      Excellence for the Medical Consequences of SCI at the James J. Peters VA Medical
      Center have devoted more than 25 years to the study of secondary medical
      conditions that complicate SCI. Herein, we review pulmonary research at the
      Center, both our past and future endeavors, which form an integral part of our
      multidisciplinary approach toward achieving a greater understanding of and
      improving care for veterans with SCI.

PMID- 24723069
TI  - Conscious sedation for upper endoscopy in the gastric bypass patient: prevalence
      of cardiopulmonary adverse events and predictors of sedation requirement.
AB  - BACKGROUND: Safety of conscious sedation for performing esophagoduodenoscopy
      (EGD) in obese and Roux-en-Y gastric bypass (RYGB) patients remains
      controversial. Additionally, it has been suggested that patients with higher body
      mass index (BMI) require higher sedation doses, imparting greater risk. AIM: The
      aim of this study is to assess the prevalence of sedation-related adverse events
      and the independent predictors of sedation requirements in RYGB patients.
      METHODS: This study is a retrospective database review of RYGB patients who
      underwent EGD under conscious sedation. Database analysis was performed and
      linear regression applied to identify significant predictors of sedation
      requirement. Primary outcomes are sedation-related adverse events and predictors
      of sedation requirement. RESULTS: Data on 1,385 consecutive procedures
      (diagnostic 967; therapeutic 418) performed under conscious sedation were
      analyzed. Unplanned events were reported in 1.6 %, with 0.6 % being
      cardiopulmonary in nature and 0.7 % requiring early termination. Multivariable
      linear regression revealed procedural time was the only significant predictor of
      fentanyl (standardized beta 0.34; P value < 0.001) and midazolam (standardized
      beta 0.30; P value < 0.001) doses. Post-RYGB BMI was not significantly associated
      with the dose of fentanyl (standardized beta 0.08; P value 0.29) or midazolam
      administered (standardized beta 0.01; P value 0.88). CONCLUSIONS: Upper endoscopy
      can be safely performed in RYGB patients under conscious sedation with a similar
      cardiopulmonary risk profile to that of standard EGD. The non-cardiopulmonary
      adverse events were procedure-specific and unrelated to sedation. Procedure
      length, and not absolute BMI, was the only predictor of sedation requirement in
      this patient population.

PMID- 24723070
TI  - Clinically severe portal hypertension: role of multi-detector row CT features in
      diagnosis.
AB  - BACKGROUND AND AIM: To explore the CT signs which permit estimation of clinically
      severe portal hypertension (PH) [>= 12 of hepatic vein pressure gradient (HVPG)].
      METHODS: One-hundred and seven consecutive patients who underwent HVPG
      measurement in the PH group and 52 controls were included. The diameters of main
      portal vein (oMPV), superior mesenteric vein (oSMV), splenic vein (oSV), and left
      gastric vein, oMPV/oSV, oSMV/oSV, as well as estimated spleen volumes were
      evaluated on the CT scan. The grade of varix and ascites were also evaluated semi
      quantitatively. We explored the statistically significant CT features related to
      severe PH and performed a logistic regression analysis for an estimation model
      for severe PH. RESULTS: oMPV/oSV and oSMV/oSV tended to gradually increase as the
      PH became severer, and the difference between severe and not severe groups was
      statistically significant (p = 0.015 and 0.038, respectively). According to the
      regression analysis, oSMV/oSV and the grade of esophageal varix and ascites were
      finally included as related variables for predicting severe PH. The odds ratio
      (OR) of oSMV/oSV was 4.596, and large esophageal varix (OR 4.135) and mild (OR
      3.051) and large amount of ascites (OR 21.781) were statistically significantly
      related to severe PH. CONCLUSION: Changing diameters of portal system, the grades
      of esophageal varices and ascites on multi-detector row computed tomography might
      be indicative features for clinically severe PH.

PMID- 24723071
TI  - Do we need colonoscopy following acute diverticulitis detected on computed
      tomography to exclude colorectal malignancy?
AB  - BACKGROUND: Although colonoscopy verification is warranted after an acute event
      of diverticulitis to exclude underlying malignancy, little evidence is available
      to support the recommendations. AIM: The aim of this study was to examine whether
      subsequent colonoscopy is warranted in patients with diverticulitis on computed
      tomography (CT). METHODS: The study was composed of patients diagnosed with acute
      diverticulitis on CT scan from January 2001 to March 2013. Patients who had
      subsequent colonoscopy within a year from the date of CT were included. For each
      diverticulitis case, two age- (+/- 5 years) and sex-matched controls were
      identified from healthy individuals who had received screening colonoscopy. We
      evaluated the diagnostic yield of advanced colonic neoplasia in colonoscopy.
      RESULTS: One hundred and forty-nine patients underwent subsequent colonoscopy
      within a year from the date of CT. Among the patients, 11 (7.4 %) had colon
      cancer and 5 (3.4 %) had advanced adenoma. A case-control study revealed that the
      odds of detecting an advanced neoplasia among patients with diverticulitis on CT
      were approximately 8.8 times greater than in the age- and sex-matched controls
      [OR 8.84; 95 % CI 2.90-26.96; p < 0.001]. On analysis of the diverticulitis
      group, age (>= 50 years) is an independent risk factor for detecting advanced
      colonic neoplasia. CONCLUSIONS: The yield of advanced colonic neoplasia was
      substantially higher in patients with acute diverticulitis than in asymptomatic,
      average-risk individuals. Colonoscopy verification is warranted in patients with
      diverticulitis detected on CT, especially in those aged 50 years or older.

PMID- 24723072
TI  - Phosphoinositide 3-kinase pathway mediates early aldosterone action on morphology
      and epithelial sodium channel in mammalian renal epithelia.
AB  - Involvement of phosphoinositide 3-kinases (PI3Ks) in early aldosterone action on
      epithelial sodium channel (ENaC) in mammalian renal epithelia was investigated by
      hopping probe ion conductance microscopy combined with patch-clamping in this
      study. Aldosterone treatment enlarged the cell volume and elevated the apical
      membrane of renal mpkCCDc14 epithelia, which resulted in enhancing the open
      probability of ENaC. Inhibition of PI3K pathway by LY294002 obviously suppressed
      these aldosterone-induced changes in both cell morphology and ENaC activity.
      These results indicated the important role of PI3K pathway in early aldosterone
      action and the close relationship between cell morphology and ENaC activity in
      mammalian renal epithelia. 

PMID- 24723073
TI  - The relationship between muscle alpha-tocopherol concentration and meat oxidation
      in light lambs fed vitamin E supplements prior to slaughter.
AB  - BACKGROUND: The use of concentrates supplemented with alpha-tocopherol in animals
      is an effective method to reduce the oxidative processes that occur in meat
      products. The high cost of alpha-tocopherol requires accurate feeding, so it is
      necessary to define the minimum period of alpha-tocopherol concentrate
      supplementation that will ensure an acceptable meat quality. Indoor concentrate
      fed light lambs (n = 35) were supplemented with 500 mg dl-alpha-tocopheryl
      acetate (VE) kg(-1) concentrate for a period of between 4 and 28 days before
      being slaughtered at 22-24 kg body weight. Control lambs (n = 12) were not
      supplemented with alpha-tocopherol. RESULTS: The alpha-tocopherol content in both
      plasma and muscle tissues increased significantly with the length of
      supplementation (P < 0.001). The thiobarbituric acid-reactive substance (TBARS)
      concentration in meat decreased exponentially when the muscle alpha-tocopherol
      concentration was increased to 0.61-0.90 mg kg(-1) fresh meat (P < 0.05). After 7
      days of display, the formation of metmyoglobin (MMb) decreased significantly as
      the alpha-tocopherol content increased to 0.31-0.60 mg kg(-1) meat (P < 0.05).
      CONCLUSION: A range of 0.61-0.90 mg alpha-tocopherol kg(-1) fresh meat protected
      fresh lamb meat from lipid oxidation and MMb formation. This level can be
      achieved by supplementation with 500 mg VE kg(-1) concentrate for a period of 7
      14 days before slaughter.

PMID- 24723074
TI  - Conformational landscapes for KMSKS loop in tyrosyl-tRNA synthetases.
AB  - Protein synthesis requires accurate charging of tRNA with cognate amino acid as
      catalyzed by aminoacyl-tRNA synthetases. Crystal structures of tyrosyl-tRNA
      synthetase (YRSs) show remarkably diverse conformations for the KMSKS loop,
      hitherto classified as "open" and "closed". This traditional classification
      implied that the KMSKS loop adopts different conformations depending on occupancy
      of active site pocket. Our structural analyses of evolutionarily derived ensemble
      of differentially ligated YRSs using quantitative structural criterion
      demonstrate intrinsic conformational heterogeneity in KMSKS loop that is
      independent of occupancy of active site. Differential centroid distance analyses
      between KMSKS motif and Rossmann fold domain reveal an intriguing bimodal
      distribution. These insights have been used for a more consistent re
      classification of YRS conformations as either compact or extended. Our data not
      only reflect inherent dynamics within the conformational landscape of KMSKS
      loops, but also have implications for structure-based drug design efforts. 

PMID- 24723075
TI  - Baseline very low-density lipoprotein cholesterol is associated with the
      magnitude of triglyceride lowering on statins, fenofibric acid, or their
      combination in patients with mixed dyslipidemia.
AB  - Fibric acid derivatives like fenofibric acid (FA) decrease hepatic production of
      very low-density lipoprotein (VLDL)-associated triglycerides (TG). Hepatic VLDL
      production can be estimated from VLDL-associated cholesterol (VLDL-C). We
      assessed if the degree of TG reduction observed with FA, statins, or their
      combination is associated with baseline VLDL-C. Overall, 2,715 patients with
      mixed dyslipidemia in three randomized, controlled studies were assigned to one
      of six treatment strategies: FA, low-dose statin (LDS), FA + LDS, moderate-dose
      statin (MDS), FA + MDS, and high-dose statin (HDS). Patients were dichotomized
      into low- or high-baseline VLDL-C groups. Pooled data were used to compare the
      degree of TG reduction in patients with low- vs. high-baseline VLDL-C for each
      treatment arm, using unpaired, two-sided t test. Additionally, the association
      between baseline VLDL-C level and percentage TG reduction from baseline was
      evaluated by linear regression. Diagnostic performance of baseline VLDL-C levels
      in predicting 5, 10, 15, and 20% TG reduction was assessed by receiver operating
      characteristics (ROC) analysis. In all treatment groups, following 12 weeks of
      therapy, a significantly greater percent change from baseline in TG was observed
      in the high-baseline VLDL-C group as compared with the low-baseline VLDL-C group.
      Linear regression analysis indicated that approximately 6 to 13% of the decrease
      in TG could be explained by baseline VLDL-C. ROC-derived cut points for baseline
      VLDL-C were obtained for 5, 10, 15, and 20% TG reduction. Baseline VLDL-C levels
      are associated with the degree of TG lowering using FA, statins, or their
      combination, thereof.

PMID- 24723076
TI  - Iris stromal cyst management with absolute alcohol-induced sclerosis in 16
      patients.
AB  - IMPORTANCE: The management of symptomatic iris stromal cyst is challenging using
      methods of aspiration with or without adjunctive cryotherapy, intracameral
      cautery, or photocoagulation. Failed cases often require surgical resection, with
      risks for epithelial downgrowth, glaucoma, blindness, and loss of the eye.
      OBJECTIVE: To study the safety and efficacy of the management of iris stromal
      cysts with aspiration and alcohol irrigation to induce cyst sclerosis. DESIGN,
      SETTING, AND PARTICIPANTS: Interventional case series at a tertiary referral
      center among 16 patients. EXPOSURES: Microscopically monitored transcorneal
      aspiration of cysts was performed with a 30-gauge needle on a 3-way T-extension
      into a 3-mL syringe, followed by immediate infusion of absolute alcohol from a
      separate 1-mL syringe through the other arm of the T-extension. Subsequent
      alcohol aspiration and repetition of the cycle was performed until the collapsed
      cyst wall appeared gray. MAIN OUTCOMES AND MEASURES: Cyst involution, visual
      acuity, and treatment complications. RESULTS: The iris stromal cysts were primary
      congenital (n = 6), primary acquired (n = 4), or secondary (n = 6). The cysts had
      a median basal diameter of 12 mm and a thickness of 4 mm, occupying 50% or more
      of the anterior or posterior chamber in each case. Treatment was administered
      following failure of simple aspiration (n = 16) and additional methods (n = 8).
      During a median follow-up period of 5 years, treatment was successful in 14 of 15
      patients (1 patient was lost to follow-up). Cyst sclerosis with stabilization (n
      = 1) or involution (n = 13) was achieved following 1 (n = 10), 2 (n = 2), or 3 (n
      = 2) procedures. The single failure occurred in a 3-year-old child with cyst
      recurrence and severe photophobia requiring resection. Visual acuity remained
      stable or had improved in 14 patients and was reduced in 1 patient because of
      cataract. Complications included transient corneal edema (n = 4) and transient
      anterior chamber inflammation (n = 1), which resolved following topical
      corticosteroid therapy. No evidence was seen of treatment-related glaucoma,
      epithelial downgrowth, tissue necrosis, cataract, posterior segment toxic
      effects, or need for enucleation. CONCLUSIONS AND RELEVANCE: Microscopically
      monitored aspiration and absolute alcohol-induced sclerosis of iris stromal cysts
      is safe and effective, with cyst involution obtained in 93% (14 of 15) of
      patients.

PMID- 24723077
TI  - Hepatic decompensation in antiretroviral-treated patients co-infected with HIV
      and hepatitis C virus compared with hepatitis C virus-monoinfected patients: a
      cohort study.
AB  - BACKGROUND: The incidence and determinants of hepatic decompensation have been
      incompletely examined among patients co-infected with HIV and hepatitis C virus
      (HCV) in the antiretroviral therapy (ART) era, and few studies have compared
      outcome rates with those of patients with chronic HCV alone. OBJECTIVE: To
      compare the incidence of hepatic decompensation between antiretroviral-treated
      patients co-infected with HIV and HCV and HCV-monoinfected patients and to
      evaluate factors associated with decompensation among co-infected patients
      receiving ART. DESIGN: Retrospective cohort study. SETTING: Veterans Health
      Administration. PATIENTS: 4280 co-infected patients who initiated ART and 6079
      HCV-monoinfected patients receiving care between 1997 and 2010. All patients had
      detectable HCV RNA and were HCV treatment-naive. MEASUREMENTS: Incident hepatic
      decompensation, determined by diagnoses of ascites, spontaneous bacterial
      peritonitis, or esophageal variceal hemorrhage. RESULTS: The incidence of hepatic
      decompensation was greater among co-infected than monoinfected patients (7.4% vs.
      4.8% at 10 years; P < 0.001). Compared with HCV-monoinfected patients, co
      infected patients had a higher rate of hepatic decompensation (hazard ratio [HR]
      accounting for competing risks, 1.56 [95% CI, 1.31 to 1.86]). Co-infected
      patients who maintained HIV RNA levels less than 1000 copies/mL still had higher
      rates of decompensation than HCV-monoinfected patients (HR, 1.44 [CI, 1.05 to
      1.99]). Baseline advanced hepatic fibrosis (FIB-4 score >3.25) (HR, 5.45 [CI,
      3.79 to 7.84]), baseline hemoglobin level less than 100 g/L (HR, 2.24 [CI, 1.20
      to 4.20]), diabetes mellitus (HR, 1.88 [CI, 1.38 to 2.56]), and nonblack race
      (HR, 2.12 [CI, 1.65 to 2.72]) were each associated with higher rates of
      decompensation among co-infected patients. LIMITATION: Observational study of
      predominantly male patients. CONCLUSION: Despite receiving ART, patients co
      infected with HIV and HCV had higher rates of hepatic decompensation than HCV
      monoinfected patients. Rates of decompensation were higher for co-infected
      patients with advanced liver fibrosis, severe anemia, diabetes, and nonblack
      race. PRIMARY FUNDING SOURCE: National Institutes of Health.

PMID- 24723078
TI  - Variation in diagnostic coding of patients with pneumonia and its association
      with hospital risk-standardized mortality rates: a cross-sectional analysis.
AB  - BACKGROUND: Most U.S. hospitals publicly report 30-day risk-standardized
      mortality rates for pneumonia. Rates exclude severe cases, which may be assigned
      a secondary diagnosis of pneumonia and a principal diagnosis of sepsis or
      respiratory failure. By assigning sepsis and respiratory failure codes more
      liberally, hospitals might improve their reported performance. OBJECTIVE: To
      examine the effect of the definition of pneumonia on hospital mortality rates.
      DESIGN: Cross-sectional study. SETTING: 329 U.S. hospitals. PATIENTS: Adults
      hospitalized for pneumonia (as a principal diagnosis or secondary diagnosis
      paired with a principal diagnosis of sepsis or respiratory failure) between 2007
      and 2010. MEASUREMENTS: Proportion of patients with pneumonia coded with a
      principal diagnosis of sepsis or respiratory failure and risk-standardized
      mortality rates excluding versus including a principal diagnosis of sepsis or
      respiratory failure. RESULTS: When the definition of pneumonia was limited to
      patients with a principal diagnosis of pneumonia, the risk-standardized mortality
      rate was significantly better than the mean in 4.3% of hospitals and
      significantly worse in 6.4%. When the definition was broadened to include
      patients with a principal diagnosis of sepsis or respiratory failure, this rate
      was better than the mean in 11.9% of hospitals and worse in 22.8% and the outlier
      status of 28.3% of hospitals changed. Among hospitals in the highest quintile of
      proportion of patients coded with a principal diagnosis of sepsis or respiratory
      failure, outlier status under the broader definition improved in 7.6% and
      worsened in 40.9%. Among those in the lowest quintile, 20.0% improved and none
      worsened. LIMITATION: Only inpatient mortality was studied. CONCLUSION: Variation
      in use of the principal diagnosis of sepsis or respiratory failure may bias
      efforts to compare hospital performance regarding pneumonia outcomes. PRIMARY
      FUNDING SOURCE: Agency for Healthcare Research and Quality.

PMID- 24723080
TI  - Behavioral counseling research and evidence-based practice recommendations: U.S.
      Preventive Services Task Force perspectives.
AB  - The U.S. Preventive Services Task Force (USPSTF) makes recommendations on which
      preventive services to routinely incorporate into primary care for specific
      populations. Behavioral counseling interventions are preventive services designed
      to help persons engage in healthy behaviors and limit unhealthy ones. The
      USPSTF's evaluation of behavioral counseling interventions asks 2 primary
      questions: Do interventions in the clinical setting influence persons to change
      their behavior, and does changing health behavior improve health outcomes with
      minimal harms?This article discusses challenges encountered by the USPSTF in
      aggregating the behavioral counseling intervention literature to develop
      guidelines. The challenges relate broadly to study populations, intervention
      protocols, assessment of outcomes, and linking behavior changes to health
      outcomes. Recommendations to address these challenges include use of the PRECIS
      (Pragmatic-Explanatory Continuum Indicator Summary) tool as a guide for the
      development of feasible, replicable, and generalizable behavioral counseling
      interventions; improved reporting of study methods and results; consensus
      measures for key behavioral outcomes; and use of existing data sets to link
      behavior change and clinical outcomes. 

PMID- 24723079
TI  - Association of dietary, circulating, and supplement fatty acids with coronary
      risk: a systematic review and meta-analysis.
AB  - BACKGROUND: Guidelines advocate changes in fatty acid consumption to promote
      cardiovascular health. PURPOSE: To summarize evidence about associations between
      fatty acids and coronary disease. DATA SOURCES: MEDLINE, Science Citation Index,
      and Cochrane Central Register of Controlled Trials through July 2013. STUDY
      SELECTION: Prospective, observational studies and randomized, controlled trials.
      DATA EXTRACTION: Investigators extracted data about study characteristics and
      assessed study biases. DATA SYNTHESIS: There were 32 observational studies
      (530,525 participants) of fatty acids from dietary intake; 17 observational
      studies (25,721 participants) of fatty acid biomarkers; and 27 randomized,
      controlled trials (103,052 participants) of fatty acid supplementation. In
      observational studies, relative risks for coronary disease were 1.02 (95% CI,
      0.97 to 1.07) for saturated, 0.99 (CI, 0.89 to 1.09) for monounsaturated, 0.93
      (CI, 0.84 to 1.02) for long-chain omega-3 polyunsaturated, 1.01 (CI, 0.96 to
      1.07) for omega-6 polyunsaturated, and 1.16 (CI, 1.06 to 1.27) for trans fatty
      acids when the top and bottom thirds of baseline dietary fatty acid intake were
      compared. Corresponding estimates for circulating fatty acids were 1.06 (CI, 0.86
      to 1.30), 1.06 (CI, 0.97 to 1.17), 0.84 (CI, 0.63 to 1.11), 0.94 (CI, 0.84 to
      1.06), and 1.05 (CI, 0.76 to 1.44), respectively. There was heterogeneity of the
      associations among individual circulating fatty acids and coronary disease. In
      randomized, controlled trials, relative risks for coronary disease were 0.97 (CI,
      0.69 to 1.36) for alpha-linolenic, 0.94 (CI, 0.86 to 1.03) for long-chain omega-3
      polyunsaturated, and 0.89 (CI, 0.71 to 1.12) for omega-6 polyunsaturated fatty
      acid supplementations. LIMITATION: Potential biases from preferential publication
      and selective reporting. CONCLUSION: Current evidence does not clearly support
      cardiovascular guidelines that encourage high consumption of polyunsaturated
      fatty acids and low consumption of total saturated fats. PRIMARY FUNDING SOURCE:
      British Heart Foundation, Medical Research Council, Cambridge National Institute
      for Health Research Biomedical Research Centre, and Gates Cambridge.

PMID- 24723081
TI  - After the revolution: DRGs at age 30.
AB  - 1 October 2013 marked 30 years since Medicare began paying hospitals by diagnosis
      related group (DRG), arguably the most influential innovation in the history of
      health care financing. Initially developed as a tool for hospital management,
      DRGs became the basis of the inpatient prospective payment system that Medicare
      implemented in 1983. The strong incentives were revolutionary in their impact.
      Medicare spending growth slowed sharply, and, more remarkable, hospitals posted
      record profits. After the link between cost and payment was broken, hospitals
      moved quickly to cut costs. Nevertheless, a literature survey concluded that none
      of the worst fears about adverse effects on patients were realized. Diagnosis
      related groups have also come to define "the product of a hospital" for purposes
      of benchmarking and risk adjustment. The acceptance of DRG algorithms owes much
      to their categorical approach, clinical focus, and transparency. The 2 most
      commonly used algorithms, Medicare DRGs and All Patient Refined (APR) DRGs,
      typically explain more than 40% of cost variance in inpatient stays, although
      with considerable range by care category. Because Medicare DRGs are unsuitable
      for obstetrics, pediatrics, and neonatology, some payers prefer APR DRGs.
      Diagnosis-related groups have proven to be a suitable basis for payment, as
      evidenced by widespread use. Common issues include mitigation of adverse
      incentives, appropriate payment for extremely costly stays, applicability to
      certain hospitals and care categories, and growing complexity. The DRG experience
      offers lessons about the effectiveness of financial incentives, the likelihood of
      adverse effects, the usefulness of case-mix measures, the risks of growing
      complexity, and the example that sensible policy need not be the domain of any
      one political party or other entity. 

PMID- 24723082
TI  - Measuring pneumonia-related mortality using administrative data: coding and
      consequences.

PMID- 24723083
TI  - Reflections on a whipple.

PMID- 24723084
TI  - Comparative safety of vascular closure devices.

PMID- 24723085
TI  - Decision time.

PMID- 24723086
TI  - A review of CT-P13: an infliximab biosimilar.
AB  - CT-P13 (RemsimaTM; InflectraTM), a biosimilar of reference infliximab
      (Remicade((r))), is approved by the European Medicines Agency for use in all
      indications for which reference infliximab is approved, including rheumatoid
      arthritis, ankylosing spondylitis, Crohn's disease, ulcerative colitis, psoriatic
      arthritis and psoriasis. Infliximab is a chimeric human-murine monoclonal
      antibody against the proinflammatory cytokine tumour necrosis factor-alpha. The
      CT-P13 infliximab formulation is identical to that of reference infliximab and it
      has similar physiochemical characteristics. The approval of CT-P13 was based on
      the results of a rigorous, comparability exercise. This article reviews the
      results of that exercise, focusing on the clinical evaluation programme. In two
      well-designed clinical trials, CT-P13 was equivalent to reference infliximab in
      terms of pharmacokinetic properties in patients with ankylosing spondylitis and
      in terms of efficacy in patients with rheumatoid arthritis. In both studies, CT
      P13 was generally well tolerated with a similar tolerability profile to that of
      reference infliximab. Immunogenicity evaluations demonstrated that the proportion
      of patients developing anti-drug antibodies was similar with each agent.
      Preliminary data from trial extensions demonstrated that in patients who switched
      from reference infliximab to CT-P13, efficacy was sustained and similar to those
      who were treated continuously with CT-P13. As with all biosimilar and generic
      agents, CT-P13 has the potential to reduce treatment costs compared with those of
      reference infliximab, and modelled analyses predict significant cost savings
      compared with reference infliximab. In conclusion, CT-P13 is an infliximab
      biosimilar that provides a useful alternative to reference infliximab in patients
      requiring infliximab therapy. 

PMID- 24723088
TI  - Characterization and gene deletion analysis of four homologues of group 3
      pyridine nucleotide disulfide oxidoreductases from Thermococcus kodakarensis.
AB  - Enzymatic characterization of the four group 3 pyridine nucleotide disulfide
      oxidoreductase (PNDOR) homologues TK1299, TK0304, TK0828, and TK1481 from
      Thermococcus kodakarensis was performed, with a focus on their CoA-dependent
      NAD(P)H: elemental sulfur (S(0)) oxidoreductase (NSR) and NAD(P)H oxidase (NOX)
      activities. TK1299 exhibited NSR activity with a preference for NADPH and showed
      strict CoA-dependency similar to that of the Pyrococcus furiosus homologue
      PF1186. During the assays, the non-enzymatic formation of H2S from S(0) and free
      CoA-SH was observed, and the addition of enzyme and NADPH enhanced H2S evolution.
      A catalytic cycle of TK1299 was proposed suggesting that CoA-SH acted to
      solubilize S(0) by forming CoA persulfides, followed by reduction of an enzyme-S
      S-CoA intermediate produced after both enzymatic and non-enzymatic evolution of
      H2S from the CoA persulfide, with NADPH as an electron donor. TK1481 showed NSR
      activity independently of CoA-SH, implying a direct reaction with S(0). TK1299,
      TK1481, and TK0304 exhibited high NOX activity, and the NADH-dependent activities
      were inhibited by the addition of free CoA-SH. Multiple disruptions of the four
      group 3 PNDOR homologues in T. kodakarensis demonstrated that none of these
      homologues were essential for S(0)-dependent growth. Many disruptants grew better
      than the parent strain, but a few multiple disruptants showed decreased growth
      properties after aerobic inoculation into a pyruvate-containing medium without
      S(0), suggesting the complicated participation of these group 3 PNDORs in
      sensitivity/resistance to dissolved oxygen when S(0) was absent.

PMID- 24723089
TI  - [Acral necrosis as a complication of urosepsis].
AB  - Sepsis is the third most common cause of death in Germany. Every fourth patient
      with sepsis has urosepsis. Even if substantial therapeutic progress has been
      made, sepsis remains a severe condition with high morbidity and mortality that
      requires rapid interdisciplinary measures. Besides life-threatening
      complications, acral necrosis as presented here can occur as a result of
      disseminated intravascular coagulation and severe microcirculatory disorders. 

PMID- 24723087
TI  - Management of fulminant myocarditis: a diagnosis in search of its etiology but
      with therapeutic options.
AB  - Fulminant myocarditis is a clinical syndrome with signs of acute heart failure,
      cardiogenic shock, or life-threating rhythm disturbances in the context of
      suspected myocarditis. It is not an etiological diagnosis, but may have different
      underlying causes and pathogenetic processes - viral, bacterial, toxic, and
      autoreactive. Clinical management of the disease entity at the acute stage
      involves hemodynamic monitoring in an intensive care unit or similar setting.
      Rapid routine work-up is mandatory with serial EKGs, echocardiography, cardiac
      MRI, heart catheterization with endomyocardial biopsy for histology,
      immunohistology, and molecular analysis for the underlying infection and
      pathogenesis. Heart failure therapy is warranted in all cases according to
      current guidelines. For fulminant autoreactive myocarditis, immunosuppressive
      treatment is beneficial; for viral myocarditis, IVIg can resolve the
      inflammation, reduce the viral load, and even eradicate the microbial agent.
      ECMO, IABP, ventricular assist devices, LifeVest, or ICD implantation can bridge
      to recovery or to heart transplantation. 

PMID- 24723090
TI  - [Biopsies of the kidney, prostate and urinary bladder].
AB  - BACKGROUND: Biopsies of the kidney, prostate and urinary bladder are amongst the
      most frequent interventions in urology. A correct indication, preparation and
      performance are important to achieve good results and low complication rates.
      OBJECTIVES: In this review complication management in biopsies of the kidney,
      prostate and urinary bladder are discussed. MATERIALS AND METHODS: A selective
      search of the literature, with emphasis on systematic reviews and larger cohort
      studies was performed. RESULTS: Complication rates are generally low. However,
      certain factors such as coagulation disorders, anatomical malformations,
      accompanying morbidities or antibiotic resistance may play a significant role and
      increase rates of complications. Especially complications such as hematuria and
      injury of contiguous organs are described in the literature. DISCUSSION: Biopsies
      of the kidney, prostate and urinary bladder can be performed with low
      complication rates if general and specific factors in the planning of the
      intervention and prevention of complications are considered.

PMID- 24723091
TI  - Safety and tolerance of a new extensively hydrolyzed rice protein-based formula
      in the management of infants with cow's milk protein allergy.
AB  - Guidelines recommend the use of extensively hydrolyzed cow's milk protein-based
      formulas (eHF) in the treatment of infants with cow's milk protein allergy
      (CMPA). Extensively hydrolyzed rice protein infant formula (eRHF) has recently
      become available and could offer a valid alternative. A prospective trial was
      performed to evaluate the hypo-allergenicity and safety of a new eRHF in infants
      with a confirmed CMPA. Patients were fed the study formula for 6 months. Clinical
      tolerance of the eRHF was evaluated with a symptom-based score (SBS) and growth
      (weight and length) was monitored. Forty infants (mean age, 3.4 months; range, 1
      6 months) with CMPA confirmed by a food challenge were enrolled. All infants
      tolerated the eRHF and the SBS significantly decreased as of the first month of
      intervention. Moreover, the eRHF allowed a catch-up to normal weight gain as of
      the first month as well as a normalization of the weight-for-age, weight-for
      length, and BMI z-scores within the 6-month study period. CONCLUSION: In
      accordance with current guidelines, this eRHF was tolerated by more than 90 % of
      children with proven CMPA with a 95 % confidence interval. This eRHF is an
      adequate and safe alternative to cow milk-based eHF.

PMID- 24723092
TI  - The value of DNA storage and pedigree analysis in rare diseases: a 17-year-old
      boy with X-linked lymphoproliferative disease (XLP) caused by a de novo SH2D1A
      mutation.
AB  - We present a case of a fatal Epstein-Barr infection in a 17-year-old male patient
      suspected to be caused by X-linked lymphoproliferative disease. At the time of
      hospitalization, DNA diagnostics was not available. The suspected diagnosis was
      confirmed several years later when a SH2D1A missense mutation was identified in
      stored patient DNA. Extended pedigree analysis showed that this mutation occurred
      de novo in his mother. In addition, we provide a summary of the currently listed
      SH2D1A mutations. CONCLUSION: This case report underlines the importance of DNA
      storage, pedigree analysis, and multidisciplinary care in patients with rare
      diseases and their families.

PMID- 24723093
TI  - Beyond post-synthesis modification: evolution of metal-organic frameworks via
      building block replacement.
AB  - Metal-organic frameworks (MOFs) are hybrid porous materials with many potential
      applications, which intimately depend on the presence of chemical functionality
      either at the organic linkers and/or at the metal nodes. Functionality that
      cannot be introduced into MOFs directly via de novo syntheses can be accessed
      through post-synthesis modification (PSM) on the reactive moieties of the linkers
      and/or nodes without disrupting the metal-linker bonds. Even more intriguing
      methods that go beyond PSM are herein termed building block replacement (BBR)
      which encompasses (i) solvent-assisted linker exchange (SALE), (ii) non-bridging
      ligand replacement, and (iii) transmetalation. These one-step or tandem BBR
      processes involve exchanging key structural components of the MOF, which in turn
      should allow for the evolution of protoMOF structures (i.e., the utilization of a
      parent MOF as a template) to design MOFs composed of completely new components,
      presumably via single crystal to single crystal transformations. The influence of
      building block replacement on the stability and properties of MOFs will be
      discussed, and some insights into their mechanistic aspects are provided. Future
      perspectives providing a glimpse into how these techniques can lead to various
      unexplored areas of MOF chemistry are also presented. 

PMID- 24723094
TI  - A facile and general route to 3-((trifluoromethyl)thio)benzofurans and 3
      ((trifluoromethyl)thio)benzothiophenes.
AB  - A facile and general route to 3-((trifluoromethyl)thio)benzofurans and 3
      ((trifluoromethyl)thio)benzothiophenes is reported. The reactions of
      trifluoromethanesulfanylamide with 1-methoxy-2-alkynylbenzenes or methyl(2
      alkynylphenyl)sulfanes promoted by BiCl3 proceed smoothly with broad functional
      group tolerance. 

PMID- 24723096
TI  - Bioaccumulation and speciation of selenium in fish and insects collected from a
      mountaintop removal coal mining-impacted stream in West Virginia.
AB  - A major contaminant of concern for mountaintop removal/valley fill (MTR/VF) coal
      mining is selenium (Se), an essential micronutrient that can be toxic to fish.
      Creek chubs (Semotilus atromaculatus), green sunfish (Lepomis cyanellus), and
      composite insect samples were collected in March-July, 2011-2013 at two sites
      within the Mud River, West Virginia. One site (MR7) receives MTR/VF coal mining
      effluent, while the reference site (LFMR) does not. MR7 water had significantly
      higher concentrations of soluble Se (p < 0.01) and conductivity (p < 0.005)
      compared to LFMR. MR7 whole insects contained significantly higher concentrations
      of Se compared to LFMR insects (p < 0.001). MR7 creek chubs had significantly
      higher Se in fillets, liver, and ovary tissues compared to LFMR samples (p <
      0.0001, p < 0.0001, and p < 0.02, respectively). MR7 green sunfish fillets
      contained significantly higher Se (p < 0.0001). Histological examination showed
      LFMR creek chub gills contained a typical amount of parasitic infestations;
      however MR7 gills contained minimal to no visible parasites. X-ray absorption
      spectroscopic analyses revealed that MR7 whole insects and creek chub tissues
      primarily contained organic Se and selenite. These two species of Mud River fish
      were shown to specifically accumulate Se differently in tissues compartments.
      Tissue-specific concentrations of Se may be useful in determining potential
      reproductive consequences of Se exposure in wild fish populations.

PMID- 24723097
TI  - An extraordinary case of an intracranial foreign body after a gunshot to the
      head.
AB  - Intermediate targets (IT) can modify the morphology of an entrance wound, the
      trajectory of the bullet, and contaminate the path with fragments or material
      from the target. The penetration into the body of big fragments or even of an
      entire IT is exceptional and only rarely reported in the literature. The
      interpretation of a gunshot wound after contact of the bullet with IT can
      sometimes be very tricky as the classical morphology can be missing. The
      presented case is a rare example of atypical entrance wound and path due to a
      surprising intermediate target of a gunshot fired against the head.

PMID- 24723100
TI  - Isolation and characterization of novel lipase gene LipHim1 from the DNA isolated
      from soil samples.
AB  - Metagenomics is a magnificent tool to isolate genes from unknown/uncharacterized
      species and also from organisms that cannot be cultured. In this study, we
      constructed a metagenomic library from isolated DNA of soil samples collected
      from Palamuru University campus premises, in Mahabubnagar district of Andhra
      Pradesh, India. We isolated a novel lipase gene LipHim1, which has an open
      reading frame of 591 base pairs and encodes ~23 kDa protein consisting of 196
      amino acids. The Lipase LipHim1 showed maximum 32% homology at the protein level
      with the extracellular Aeromonas hydrophila lipase (Class II, GDSL family) and
      was significantly different from all other known lipases. The isolated lipase
      catalyzed the hydrolysis of fatty acid esters of polyoxyethylene sorbitan such as
      Tween 60. Our results indicate that the isolated lipase gene is novel.

PMID- 24723099
TI  - Reasoning deficits among illicit drug users are associated with aspects of
      cannabis use.
AB  - Deficits in deductive reasoning have been observed among ecstasy/polydrug users.
      The present study seeks to investigate dose-related effects of specific drugs and
      whether these vary with the cognitive demands of the task. One hundred and five
      participants (mean age 21.33, SD 3.14; 77 females, 28 males) attempted to
      generate solutions for eight one-model syllogisms and one syllogism for which
      there was no valid conclusion. All of the one-model syllogisms generated at least
      one valid conclusion and six generated two valid conclusions. In these six cases,
      one of the conclusions was classified as common and the other as non-common. The
      number of valid common inferences was negatively associated with the aspects of
      short-term cannabis use and with measures of IQ. The outcomes observed were more
      than simple post-intoxication effects since cannabis use in the 10 days
      immediately before testing was unrelated to reasoning performance. Following
      adjustment for multiple comparisons, the number of non-common valid inferences
      was not significantly associated with any of the drug-use measures. Recent
      cannabis use appears to impair the processes associated with generating valid
      common inferences while not affecting the production of non-common inferences. It
      is possible, therefore, that the two types of inference may recruit different
      executive resources, which may differ in their susceptibility to cannabis-related
      effects. 

PMID- 24723098
TI  - Profiles in fibromyalgia: algometry, auditory evoked potentials and clinical
      characterization of different subtypes.
AB  - The heterogeneity found in fibromyalgia (FM) patients has led to the
      investigation of disease subgroups, mainly based on clinical features. The aim of
      this study was to test the hypothesis that clinical FM subgroups are associated
      with different underlying pathophysiological mechanisms. Sixty-three FM patients
      were classified in type I or type II, according to the Fibromyalgia Impact
      Questionnaire (FIQ), and in mild/moderate versus severe FM, according to the
      severity of three cardinal symptoms considered in the American College of
      Rheumatology (ACR) 2010 criteria (unrefreshed sleep, cognitive problems and
      fatigue). To validate the subgroups obtained by these two classifications, we
      calculated the area under the receiver operating characteristic curves for
      various clinical variables and for two potential biomarkers of FM: Response to
      experimental pressure pain (algometry) and the amplitude/intensity slopes of the
      auditory evoked potentials (AEPs) obtained to stimuli of increasing intensity.
      The variables that best discriminated type I versus type II were those related to
      depression, while the indices of clinical or experimental pain (threshold or
      tolerance) did not significantly differ between them. The variables that best
      discriminated the mild/moderate versus severe subgroups were those related to the
      algometry. The AEPs did not allow discrimination among the generated subsets. The
      FIQ-based classification allows the identification of subgroups that differ in
      psychological distress, while the index based on the ACR 2010 criteria seems to
      be useful to characterize the severity of FM mainly based on hyperalgesia. The
      incorporation of potential biomarkers to generate or validate classification
      criteria is crucial to advance in the knowledge of FM and in the understanding of
      pathophysiological pathways. 

PMID- 24723101
TI  - Assessment of conjugal transfer of antibiotic resistance genes in Salmonella
      Typhimurium exposed to bile salts.
AB  - This study was designed to evaluate the transfer potential of antibiotic
      resistance genes in antibiotic-resistant Salmonella Typhimurium (S.
      Typhimurium(R)) in the presence of bile salts. The resistance of S.
      Typhimurium(R) to ampicillin, kanamycin, and tetracycline was increased by 64-,
      64-, and 512-fold, respectively. The highest transfer frequency from S.
      Typhimurium(R) to Escherichia coli was observed at the bile salt concentration of
      160 MUg/ml (3.8 * 10(-3) transferrants/cells). The expression of traJ and traY
      was suppressed in S. Typhimurium(R) by bile salt. This study provides useful
      information for understanding the conjugative transfer of antibiotic resistance
      genes in S. Typhimurium under intestinal conditions.

PMID- 24723102
TI  - The role as inoculum sources of Xanthomonas citri pv. citri surviving on the
      infected Satsuma mandarin fruits.
AB  - Importing citrus fruits infected by Asiatic citrus canker caused by Xanthomonas
      citri pv. citri (Xcc) can act as an inoculum source for the disease epidemic in
      citrus canker-free countries. In this study, the pathogenicity of the causal
      agent of Asiatic citrus canker surviving on infected Satsuma mandarin fruits was
      evaluated. The washing solution of infected Satsuma mandarin fruits did not cause
      lesion formation on the citrus leaves. However, a typical citrus canker lesion
      was formed on the leaves after inoculation with higher concentrations of the
      inoculum from the washing solution (washing solution II). It indicated that the
      pathogenicity of the citrus canker surviving on the symptomatic Satsuma mandarin
      fruits was not changed. Scanning electron microscopic observation showed that the
      numbers of bacterial cells on the leaves of Satsuma mandarin which inoculated
      with the washing solution directly (washing solution I) was less compared to
      those of leaves inoculated with the washing solution II. This result spports that
      the pathogenicity of Xcc surviving on Satsuma mandarin fruits may not be changed
      but that the sucessful infection of citrus caker may depend on the concentration
      of the inoculum. 

PMID- 24723103
TI  - Comparative analysis of superantigen genes in Staphylococcus xylosus and
      Staphylococcus aureus isolates collected from a single mammary quarter of cows
      with mastitis.
AB  - The purpose of this study was to analyze and compare genes encoding superantigens
      (SAgs) in Staphylococcus xylosus and Staphylococcus aureus isolates collected
      simultaneously from milk of the same cows with clinical mastitis. Genes encoding
      staphylococcal enterotoxins and enterotoxin-like proteins (sea-selu), toxic shock
      syndrome toxin 1 (tst-1) and exfoliative toxins (eta and etd) were investigated.
      It was found that among 30 isolates of S. xylosus, 16 (53.3%) harbored from 1 to
      10 SAg genes. In total, in 16 SAg positive S. xylosus, 11 different enterotoxin
      genes were detected: sec, sed, seg, seh, sei, selm, seln, selo, selp, ser, selu
      and one etd gene encoding exfoliative toxin D. The most prevalent genes were ser,
      selu, and selo. Among all the positive isolates of S. xylosus, a total of 14
      different SAg gene combinations were detected. One combination was repeated in 3
      isolates, whereas the rest were detected only once. However, in the case of S.
      aureus all the 30 isolates harbored the same combination of SAg genes: seg, sei,
      selm, seln, selo and on the basis of PFGE analysis all belonged to the same
      clonal type. Also noteworthy was the observation that SAg genes detected in S.
      aureus have also been found in S. xylosus. The findings of this study further
      extend previous observations that SAg genes are present not only in S. aureus but
      also in coagulase-negative staphylococci, including S. xylosus. Therefore, taking
      into account that the SAg genes are encoded on mobile genetic elements it is
      possible that these genes can be transferred between different species of
      coexisting staphylococci. 

PMID- 24723104
TI  - Variations in 16S rRNA-based microbiome profiling between pyrosequencing runs and
      between pyrosequencing facilities.
AB  - Pyrosequencing of 16S rRNA gene amplicons on the 454 FLX Titanium platform has
      been widely used to analyze microbiomes in various environments. However,
      different results may stem from variations among sequencing runs or among
      sequencing facilities. This study aimed to evaluate these variations between
      different pyrosequencing runs by sequencing 16S rRNA gene amplicon libraries
      generated from three sets of rumen samples twice each on the 454 FLX Titanium
      system at two independent sequencing facilities. Similar relative abundances were
      found for predominant taxa represented by large numbers of sequence reads but not
      for minor taxa represented by small numbers of sequence reads. The two sequencing
      facilities revealed different bacterial profiles with respect to both predominant
      taxa and minor taxa, including the most predominant genus Prevotella, the family
      Lachnospiraceae, and the phylum Proteobacteria. Differences in primers used to
      generate amplicon libraries may be a major source of variations in microbiome
      profiling. Because different primers and regions of 16S rRNA genes are often used
      by different researchers, significant variations likely exist among studies.
      Quantitative interpretation for relative abundance of taxa, especially minor
      taxa, from prevalence of sequence reads and comparisons of results from different
      studies should be done with caution. 

PMID- 24723105
TI  - Changes in gene expression of Actinobacillus pleuropneumoniae in response to
      anaerobic stress reveal induction of central metabolism and biofilm formation.
AB  - Actinobacillus pleuropneumoniae is an important porcine respiratory pathogen
      causing great economic losses in the pig industry worldwide. Oxygen deprivation
      is a stress that A. pleuropneumoniae will encounter during both early infection
      and the later, persistent stage. To understand modulation of A. pleuropneumoniae
      gene expression in response to the stress caused by anaerobic conditions, gene
      expression profiles under anaerobic and aerobic conditions were compared in this
      study. The microarray results showed that 631 genes (27.7% of the total ORFs)
      were differentially expressed in anaerobic conditions. Many genes encoding
      proteins involved in glycolysis, carbon source uptake systems, pyruvate
      metabolism, fermentation and the electron respiration transport chain were up
      regulated. These changes led to an increased amount of pyruvate, lactate, ethanol
      and acetate in the bacterial cells as confirmed by metabolite detection. Genes
      encoding proteins involved in cell surface structures, especially biofilm
      formation, peptidoglycan biosynthesis and lipopolysaccharide biosynthesis were up
      regulated as well. Biofilm formation was significantly enhanced under anaerobic
      conditions. These results indicate that induction of central metabolism is
      important for basic survival of A. pleuropneumoniae after a shift to an anaerobic
      environment. Enhanced biofilm formation may contribute to the persistence of this
      pathogen in the damaged anaerobic host tissue and also in the early colonization
      stage. These discoveries give new insights into adaptation mechanisms of A.
      pleuropneumoniae in response to environmental stress. 

PMID- 24723107
TI  - Identifying airborne fungi in Seoul, Korea using metagenomics.
AB  - Fungal spores are widespread and common in the atmosphere. In this study, we use
      a metagenomic approach to study the fungal diversity in six total air samples
      collected from April to May 2012 in Seoul, Korea. This springtime period is
      important in Korea because of the peak in fungal spore concentration and Asian
      dust storms, although the year of this study (2012) was unique in that were no
      major Asian dust events. Clustering sequences for operational taxonomic unit
      (OTU) identification recovered 1,266 unique OTUs in the combined dataset, with
      between 223?96 OTUs present in individual samples. OTUs from three fungal phyla
      were identified. For Ascomycota, Davidiella (anamorph: Cladosporium) was the most
      common genus in all samples, often accounting for more than 50% of all sequences
      in a sample. Other common Ascomycota genera identified were Alternaria,
      Didymella, Khuskia, Geosmitha, Penicillium, and Aspergillus. While several
      Basidiomycota genera were observed, Chytridiomycota OTUs were only present in one
      sample. Consistency was observed within sampling days, but there was a large
      shift in species composition from Ascomycota dominant to Basidiomycota dominant
      in the middle of the sampling period. This marked change may have been caused by
      meteorological events. A potential set of 40 allergy-inducing genera were
      identified, accounting for a large proportion of the diversity present
      (22.5?7.2%). Our study identifies high fungal diversity and potentially high
      levels of fungal allergens in springtime air of Korea, and provides a good
      baseline for future comparisons with Asian dust storms.

PMID- 24723106
TI  - Genetic analysis of the capsid region of norovirus GII.4 variants isolated in
      South Korea.
AB  - Norovirus is one of the major causes of non-bacterial gastroenteritis in humans.
      The aim of this study was to analyze the amino acid variation of open reading
      frame 2 of GII.4 variants in South Korea during the period from November 2006 to
      December 2012. Sixty-nine complete nucleotide sequences of open reading frame 2
      were obtained from 113 GII.4 strains. The GII.4 2006b variants were detected
      predominantly between 2006 and 2009; however, new GII.4 variants, which were
      termed the 2010 variant and the 2012 variant, emerged in 2010 and 2012,
      respectively. The number of GII.4 2006b variants steadily decreased until 2012,
      whereas the number of gastroenteritis cases caused by the new variants increased
      between 2010 and 2012. The amino acid sequence in the ORF2 region obtained in
      this study was compared with other GII.4 variants isolated in various countries.
      Amino acid variations were observed primarily at epitope sites and the
      surrounding regions. Amino acids 294, 359, 393, and 413 of the P2 subdomain were
      the most variable sites among the GII.4 variants. The information in this study
      can be useful in basic research to predict the emergence and determine the
      genetic functions of new GII.4 variants. 

PMID- 24723108
TI  - Comparative study of the marR genes within the family Enterobacteriaceae.
AB  - marR genes are members of an ancient family originally identified in Escherichia
      coli. This family is widely distributed in archaea and bacteria. Homologues of
      this family have a conserved winged helix fold. MarR proteins are involved in non
      specific resistance systems conferring resistance to multiple antibiotics.
      Extensive studies have shown the importance of MarR proteins in physiology and
      pathogenicity in Enterobacteria, but little is known about their origin or
      evolution. In this study, all the marR genes in 43 enterobacterial genomes
      representing 14 genera were identified, and the phylogenetic relationships and
      genetic parameters were analyzed. Several major findings were made. Three
      conserved marR genes originated earlier than Enterobacteriaceae and a geneloss
      event was found to have taken place in Yersinia pestis Antiqua. Three functional
      genes, rovA, hor, and slyA, were found to be clear orthologs among
      Enterobacteriaceae. The copy number of marR genes in Enterobacteriaceae was found
      to vary from 2 to 11. These marR genes exhibited a faster rate of nucleotide
      substitution than housekeeping genes did. Specifically, the regions of marR
      domain were found to be subject to strong purifying selection. The phylogenetic
      relationship and genetic parameter analyses were consistent with conservation and
      specificity of marR genes. These dual characters helped MarR to maintain a
      conserved binding motif and variable C-terminus, which are important to adaptive
      responses to a number of external stimuli in Enterobacteriaceae. 

PMID- 24723111
TI  - Characterization of rat testicular teratoma and its derived cell lines, with
      particular reference to possible mesenchymal differentiations.
AB  - The original tumor, 4 cm in diameter, was found in the left testis of a 2-month
      old SD rat. The tumor consisted of well-differentiated, mature tissues such as
      bone, cartilage, adipose tissue, smooth and skeletal muscles, skin, hair, glands
      (salivary, sebaceous, apocrine and pancreatic exocrine glands) and trachea, as
      well as nerve tissues. The tumor was diagnosed as a mature type of teratoma, a
      rare in rat testis. Cloned cell lines (named TSD-B4S and TSD-F9R) were
      established from the tumor; cellular properties of these cell lines were similar
      to each other; basically, their cultured cells exhibited vimentin-positive
      mesenchymal nature with occasional cells reacting to alpha-smooth muscle actin,
      glial fibrillary acidic protein and CD163 (a macrophage marker). The cell lines
      showed tumorigenicity when inoculated into nude mice, being composed of immature
      mesenchymal cells arranged mainly in a sheet. In TSD-B4S cells treated with
      differentiation factors, we demonstrated mesenchymal differentiations towards
      adipogenic, osteogenic and myofibrogenic cells. The cell line (TSD-B4S) would
      become a useful tool for studies on stem cell differentiation, because the
      teratoma arises from primordial germ cells like embryonic stem cells.

PMID- 24723110
TI  - Effects of acidic oligosaccharide sugar chain on amyloid oligomer-induced
      impairment of synaptic plasticity in rats.
AB  - Soluble amyloid-beta protein (Abeta) oligomers have been recognized to be early
      and key intermediates in Alzheimer's disease-related synaptic dysfunction. In
      this study, using in vitro electrophysiology, we investigated interactions of the
      acidic oligosaccharide sugar chain (AOSC), a marine-derived acidic
      oligosaccharide, with oligomeric Abeta. We found that the inhibition of long-term
      potentiation (LTP) induced by Abeta oligomers can be dose dependently reversed by
      the application of AOSC, whereas AOSC alone did not alter normal LTP induction.
      Interestingly, treatment with Abeta monomers with or without AOSC did not affect
      LTP induction. Additionally, when fresh-made Abeta was co-incubated with AOSC
      before in vitro testing, there was no impairment of LTP induction. The results
      from Western blots demonstrated that AOSC prevent the aggregation of Abeta
      oligomers. These findings indicate that AOSC may reverse Abeta oligomer-mediated
      cytotoxicity by directly disrupting the amyloid oligomer aggregation, and this
      action is concentration dependent. Thus, we propose that AOSC might be a
      potential therapeutic drug for Alzheimer's disease due to its protection against
      oligomeric Abeta-induced dysfunction of synaptic plasticity. 

PMID- 24723112
TI  - High-purity separation of cancer cells by optically induced dielectrophoresis.
AB  - Detecting and concentrating cancer cells in peripheral blood is of great
      importance for cancer diagnosis and prognosis. Optically induced
      dielectrophoresis (ODEP) can achieve high resolution and low optical intensities,
      and the electrode pattern can be dynamically changed by varied light patterns. By
      changing the projected light pattern, it is demonstrated to separate high-purity
      gastric cancer cell lines. Traditionally, the purity of cancer cell isolation by
      negative selection is 0.9% to 10%; by positive selection it is 50% to 62%. An
      ODEP technology is proposed to enhance the purity of cancer cell isolation to
      about 77%.

PMID- 24723109
TI  - Viral hepatitis C therapy: pharmacokinetic and pharmacodynamic considerations.
AB  - Chronic hepatitis C is a global health problem. To prevent or reduce
      complications, the hepatitis C virus (HCV) infection needs to be eradicated.
      There have been several developments in treating these patients since the
      discovery of the virus. As of 1 January 2014, the drugs that are approved for
      treatment of chronic HCV infection are peginterferon-alpha, ribavirin,
      boceprevir, telaprevir, simeprevir and sofosbuvir. In this review we provide an
      overview of the clinical pharmacokinetic characteristics of these agents by
      describing their absorption, distribution, metabolism and excretion. In the
      pharmacodynamic part we summarize what is known about the relationships between
      the pharmacokinetics of each drug and efficacy or toxicity. We briefly discuss
      the pharmacokinetics and pharmacodynamics of chronic hepatitis C treatment in
      special patient populations, such as patients with liver cirrhosis, renal
      insufficiency or HCV/HIV coinfection, and children. With this knowledge,
      physicians, pharmacists, nurse practitioners, etc. should be educated to safely
      and effectively treat HCV-infected patients. 

PMID- 24723113
TI  - Diffuser-aided time-domain diffuse optical imaging: a phantom study.
AB  - We present the first experimental results of time-resolved diffuser-aided diffuse
      optical imaging (DADOI) method in this paper. A self-manufactured diffuser plate
      was inserted between the optode and the surface of a scattering medium. The
      diffuser was utilized to enhance the multiple scattering that destroys the image
      information for baseline measurement of turbid medium. Therefore, the abnormality
      can be detected with the modified optical density calculation. The time-domain
      DADOI method can provide better imaging contrast and simpler imaging than the
      conventional diffuse optical tomography measurement. Besides, it also reveals
      rich depth information with temporal responses. Therefore, the DADOI offers a
      great potential to detect the breast tumor and chemotherapy monitoring in
      clinical diagnosis.

PMID- 24723114
TI  - Tomographic phase microscopy of living three-dimensional cell cultures.
AB  - A successful application of self-interference digital holographic microscopy in
      combination with a sample-rotation-based tomography module for three-dimensional
      (3-D) label-free quantitative live cell imaging with subcellular resolution is
      demonstrated. By means of implementation of a hollow optical fiber as the sample
      cuvette, the observation of living cells in different 3-D matrices is enabled.
      The fiber delivers a stable and accurate rotation of a cell or cell cluster,
      providing quantitative phase data for tomographic reconstruction of the 3-D
      refractive index distribution with an isotropic spatial resolution. We
      demonstrate that it is possible to clearly distinguish and quantitatively analyze
      several cells grouped in a "3-D cluster" as well as subcellular organelles like
      the nucleoli and local internal refractive index changes.

PMID- 24723115
TI  - Double-pass Mach-Zehnder fiber interferometer pH sensor.
AB  - A biocompatible fiber-optic pH sensor based on a unique double-pass Mach-Zehnder
      interferometer is proposed. pH responsive poly(2-hydroxyethyl methacrylate-co-2
      (dimethylamino)ethyl methacrylate) hydrogel coating on the fiber swells/deswells
      in response to local pH, leading to refractive index changes that manifest as
      shifting of interference dips in the optical spectrum. The pH sensor is tested in
      spiked phosphate buffer saline and demonstrates high sensitivity of 1.71  nm/pH,
      pH 0.004 limit of detection with good responsiveness, repeatability, and
      stability. The proposed sensor has been successfully applied in monitoring the
      media pH in cell culture experiments to investigate the relationship between pH
      and cancer cell growth.

PMID- 24723116
TI  - Neurological abnormalities predict disability: the LADIS (Leukoaraiosis And
      DISability) study.
AB  - To investigate the role of neurological abnormalities and magnetic resonance
      imaging (MRI) lesions in predicting global functional decline in a cohort of
      initially independent-living elderly subjects. The Leukoaraiosis And DISability
      (LADIS) Study, involving 11 European centres, was primarily aimed at evaluating
      age-related white matter changes (ARWMC) as an independent predictor of the
      transition to disability (according to Instrumental Activities of Daily Living
      scale) or death in independent elderly subjects that were followed up for 3
      years. At baseline, a standardized neurological examination was performed. MRI
      assessment included age-related white matter changes (ARWMC) grading (mild,
      moderate, severe according to the Fazekas' scale), count of lacunar and non
      lacunar infarcts, and global atrophy rating. Of the 633 (out of the 639 enrolled)
      patients with follow-up information (mean age 74.1 +/- 5.0 years, 45 % males),
      327 (51.7 %) presented at the initial visit with >=1 neurological abnormality and
      242 (38 %) reached the main study outcome. Cox regression analyses, adjusting for
      MRI features and other determinants of functional decline, showed that the
      baseline presence of any neurological abnormality independently predicted
      transition to disability or death [HR (95 % CI) 1.53 (1.01-2.34)]. The hazard
      increased with increasing number of abnormalities. Among MRI lesions, only ARWMC
      of severe grade independently predicted disability or death [HR (95 % CI) 2.18
      (1.37-3.48)]. In our cohort, presence and number of neurological examination
      abnormalities predicted global functional decline independent of MRI lesions
      typical of the aging brain and other determinants of disability in the elderly.
      Systematically checking for neurological examination abnormalities in older
      patients may be cost-effective in identifying those at risk of functional
      decline.

PMID- 24723117
TI  - MRI measures of neurodegeneration in multiple sclerosis: implications for
      disability, disease monitoring, and treatment.
AB  - Magnetic resonance imaging (MRI) techniques, such as T2-weighted and gadolinium
      enhanced T1-weighted sequences, have long been used to diagnose multiple
      sclerosis (MS). However, these methods are limited in their ability to depict
      underlying disease pathology. A PubMed literature search was conducted to
      identify the publications discussing MRI in MS from 2010 to 2013, using the
      medical subject heading terms: "multiple sclerosis" and "grey/gray matter",
      "brain atrophy", "grey/gray matter atrophy", "normal appearing white matter," and
      "cortical lesions." Recent proceedings of conferences on MRI were also used to
      identify emerging techniques. MRI-derived metrics can assess the microstructural,
      metabolic, and functional changes that occur in newly formed lesions and allow
      further characterization of diffuse degeneration in different central nervous
      system compartments across MS phenotypes. Advanced imaging techniques aim to
      complement our understanding of MS disease pathophysiology, which may facilitate
      the identification of markers that could be used to predict the clinical outcomes
      of agents in development. 

PMID- 24723118
TI  - Features of citrus terpenoid production as revealed by carotenoid, limonoid and
      aroma profiles of two pummelos (Citrus maxima) with different flesh color.
AB  - BACKGROUND: Terpenoids are major components of carotenoids, limonoids and aromas
      in citrus fruits, resulting in fruit coloration, bitterness and aroma. In this
      study the carotenoid, limonoid and volatile profiles of red-flesh Chuhong pummelo
      (CH) and pale green-flesh Feicui pummelo (FC) were investigated by HPLC and
      GC/MS. RESULTS: Large differences were found in constituents of carotenoids and
      limonoids in juice sacs and flavedo and of aromas in flavedo of the two pummelos.
      For carotenoids in juice sacs, CH contained 57 times the amount in FC, mainly all
      trans-lycopene and phytoene, whereas in flavedo it contained only 25% of that in
      FC, the latter showing a high proportion of beta-carotene and other chloroplastic
      carotenoids. In comparison with FC, limonin and nomilin aglycone production was
      boosted in juice sacs of CH while being almost absent in flavedo. For volatiles
      in flavedo, the total amount was significantly higher in CH. PCA suggested that
      germacrene-type sesquiterpenoids, etc. were principal in distinguishing volatile
      profiles of the two pummelos. CONCLUSION: The data showed a different tissue
      biased pattern of carotenoid and limonoid aglycone synthesis in pummelos with
      different flesh color, and the possible independently regulated synthesis of
      those metabolites in different fruit tissues. Furthermore, decreased carotenoid
      and limonoid aglycone production accompanied by increased accumulation of
      volatile terpenoids in flavedo of red-flesh CH was identified, indicating that a
      total capacity or a balance of production of various terpenoids might exist in
      pummelo fruit tissues. It was also suggested that substrate concentration is not
      the key factor affecting product concentrations during the synthesis of
      monoterpene derivatives.

PMID- 24723119
TI  - Biosynthesis of the antibiotic tropodithietic acid by the marine bacterium
      Phaeobacter inhibens.
AB  - The biosynthesis of tropodithietic acid was investigated using a combinatorial
      approach of feeding experiments, gene knockouts and bioinformatic analyses. The
      mechanism of sulfur introduction is distinct from known mechanisms in holomycin,
      thiomarinol A and gliotoxin biosynthesis. 

PMID- 24723120
TI  - A naphthalimide-based bifunctional fluorescent probe for the differential
      detection of Hg2+ and Cu2+ in aqueous solution.
AB  - A novel fluorescent probe NPM based on naphthalimide was designed and
      synthesized. Interestingly, NPM exhibited highly selective fluorescence turn-on
      for Hg(2+) and turn-off for Cu(2+) in aqueous solution (10 mM HEPES, pH 7.5). Its
      fluorescence intensity enhanced in a linear fashion with the concentration of
      Hg(2+) and decreased in a nearly linear fashion with the concentration of Cu(2+).
      Thus NPM could be potentially used for the quantification of Hg(2+) and Cu(2+) in
      aqueous solution. A series of model compounds were rationally designed and
      synthesized in order to explore the sensing mechanisms and binding modes of NPM
      with Hg(2+) and Cu(2+). 

PMID- 24723121
TI  - Total synthesis of lycorine-type alkaloids by cyclopropyl ring-opening
      rearrangement.
AB  - A practical method for the synthesis of lycorine-type alkaloids with cis-B/C ring
      structure has been developed. Based on the reactions of aminocyclization,
      palladium-mediated arylation and especially cyclopropyl ring-opening
      rearrangement, the synthesis of anhydrocaranine, (+/-)-gamma-lycorane and
      putative (+/-)-amarbellisine was accomplished. 

PMID- 24723122
TI  - A comparison of two procedures to estimate three basic monitoring landscape
      metrics for monitoring.
AB  - An interesting alternative to wall-to-wall mapping approaches for the estimation
      of landscape metrics is to use sampling. Sample-based approaches are cost
      efficient, and measurement errors can be reduced considerably. The previous
      efforts of sample-based estimation of landscape metrics have mainly been focused
      on data collection methods, but in this study, we consider two estimation
      procedures. First, landscape metrics of interest are calculated separately for
      each sampled image and then the image values are averaged to obtain an estimate
      of the entire landscape (separated procedure, SP). Second, metric components are
      calculated in all sampled images and then the aggregated values are inserted into
      the landscape metric formulas (aggregated procedure, AP). The national land cover
      map (NLCM) of Sweden, reflecting the status of land cover in the year 2000, was
      used to provide population information to investigate the statistical performance
      of the estimation procedures. For this purpose, sampling simulation with a large
      number of replications was used. For all three landscape metrics, the second
      procedure (AP) produced a lower relative RMSE and bias than the first one (SP). A
      smaller sample unit size (50 ha) produced larger bias than a larger one (100 ha),
      whereas a smaller sample unit size produced a lower variance than a larger sample
      unit. The efficiency of a metric estimator is highly related to the degree of
      landscape fragmentation and the selected procedure. Incorporating information
      from all of the sampled images into a single one (aggregated procedure, AP) is
      one way to improve the statistical performance of estimators. 

PMID- 24723123
TI  - Soil contamination by heavy metals in landfills: measurements from an unlined
      leachate storage basin.
AB  - Landfills are sources of groundwater and soil pollution due to the production of
      leachate and its migration through refuse. This study was conducted in order to
      determine the extent of soil pollution within and around the Jebel Chakir
      landfill, located in the Tunis City, Tunisia. The main objective was to
      characterize soil samples of an unlined storage basin in relation to heavy metal
      concentrations in the Jebel Chakir landfill to the southwest of Tunis, Northern
      Tunisia. Twenty-four soil samples taken from different locations around the
      storage basin were analyzed by atomic absorption spectrophotometry for Cr, Cu,
      Ni, Pb, and Zn investigation. Our results indicated high concentrations of Cr
      (54.4-129.9 mg/kg of DM), Zn (4.1-81.8 mg/kg of DM), Ni (15.1-43.9 mg/kg of DM),
      Pb (5.6-16.1 mg/kg of DM), and Cu (0.2-1.84 mg/kg of DM). These results suggested
      that contaminant migration is controlled by an active clay layer acting as an
      insulating material in the landfill. It is therefore necessary to set a treatment
      system for the landfill leachates and place a liner under the storage basin to
      reduce the pollution threat. 

PMID- 24723125
TI  - Pathways of tumor development and progression in drug-induced nonmelanoma skin
      cancer: a new hope or the next great confusion?
AB  - The factors that lead to the clinical manifestation of the nonmelanocytic skin
      tumors are different. Ultraviolet radiation, infections with human
      papillomaviruses, and inherited or iatrogenic-induced immunosuppression (in cases
      of autoimmune diseases and organ transplant recipients) are considered to be some
      of the most important generators and/or costimulating factors supporting the
      appearance of "de-novo" mutations and obstruct, in one or another way, the cell
      cycle arrest, the programmed cell death (apoptosis), and the immunosurveillance.
      Preconditions are thus created for the initial persistence and subsequent
      proliferation of the malignant cell branch in the genome, with the simultaneous
      increase of the risk of nonmelanocytic skin tumor manifestation.A number of
      medical drugs that possess a currently well-known selective, targeting, and
      immunomodulating effect, like the TNF-alpha inhibitors for example, most probably
      possess an additional blocking action on the death receptors within the framework
      of the extrinsic apoptotic pathway. In this way, they seem to be one of the major
      factors for the clinical manifestation not only of nonmelanocytic skin but also
      of a number of other type of tumors with a dependency on the genetic
      predisposition of each separate patient.This article focuses the attention on the
      basic exogenic and endogenic factors that affect the regulatory processes of the
      cellular cycle, apoptosis, immunosurveillance, and the human inflammasome in
      patients with nonmelanocytic skin tumors. These processes are interwoven in a
      complex network and are controlled by (1) the genome regulator p53, (2) its
      interaction with the proapoptotic acting proteins Bak and Bax, (3) as well as the
      interaction with the key regulatory protein of the inflammasome-ASC/TMS1.As a
      process, the malignant transformation is exceptionally dynamic, plastic, and
      adaptive. The exterior "interferences", on the part of the clinician, in the form
      of a planned therapy should be targeted at the simultaneous impact on the various
      pathogenetic chains with the objective of bringing the tumor cells to their total
      collapse. This can be made possible only after the careful and simultaneous-or
      parallel-examination of a much greater number of markers that serve to
      characterize the process of the malignant transformation-a fact, which is
      currently being disregarded by many researchers. 

PMID- 24723126
TI  - [Influence of music on the quality of life of palliative cancer patients].
AB  - A small prospective, multicentre study examined the effect of a perceptual
      acoustic stimulus (music) on quality of life of palliative cancer patients with
      special reference to pain.14 test subjects (m = 4, w = 10; age 67.6 (SD = 9.7))
      in stationary or mobile care situation were included. The current therapy has not
      been modified.Each subject received a CD with 12 songs, an information folder, a
      guide to using the CD as well as a questionnaire.The offered music therapy was
      experienced by all study participants (100 %) as helpful. The effect was seen
      differently in psychological, physical, spiritual, and social quality of life.
      The pain was reduced nociable in 11 out of 14 participants.From the experience of
      the autors we demand to offer and enable music therapy in palliative care to each
      patient, but also adapt to their individual needs.

PMID- 24723127
TI  - Abnormalities of myocardial perfusion and glucose metabolism in patients with
      isolated left ventricular non-compaction.
AB  - BACKGROUND: The prevalence of myocardial perfusion and glucose metabolic
      abnormalities and their significance in patients with isolated left ventricular
      non-compaction (ILVNC) have not been well investigated. METHODS: Seventeen ILVNC
      patients who underwent cardiac magnetic resonance (CMR) and (99m)Tc-sestamibi
      SPECT/fluorine-18 deoxyglucose ((18)F-FDG) PET imaging were included. Left
      ventricular non-compaction, regional wall motion abnormalities, left ventricular
      ejection fraction (LVEF), and delayed enhancement (DE) were estimated using CMR.
      Myocardial perfusion and metabolism were evaluated with SPECT/PET. RESULTS:
      Ninety-five (32.9%) segments were considered non-compacted. DE was present in 52
      (18.0%) segments and 10 (58.8%) patients. The rate of occurrence of DE was
      significantly higher in compacted segments than in non-compacted segments (22.7%
      vs 8.4%, P = .003). Myocardial perfusion abnormalities were present in 92 (31.8%)
      segments, of which 66 were perfusion/metabolism match and 26 were
      perfusion/metabolism mismatch. The rate of occurrence of perfusion abnormality
      was similar between compacted and non-compacted segments (32.0% vs 31.6%, P =
      .948), but it was significantly higher in segments with DE than in those without
      DE (51.9% vs 27.4%, P = .001). None of the imaging features alone (non
      compaction, DE, perfusion abnormalities, match or mismatch) showed significant
      correlations with LVEF (all P > .05). CONCLUSION: In the current study,
      myocardial perfusion/metabolism mismatch and match were observed in both non
      compacted and compacted myocardium in ILVNC patients. Further research is
      warranted to determine their pathologic and clinical significance.

PMID- 24723124
TI  - Immunological mechanism of action and clinical profile of disease-modifying
      treatments in multiple sclerosis.
AB  - Multiple sclerosis (MS) is a life-long, potentially debilitating disease of the
      central nervous system (CNS). MS is considered to be an immune-mediated disease,
      and the presence of autoreactive peripheral lymphocytes in CNS compartments is
      believed to be critical in the process of demyelination and tissue damage in MS.
      Although MS is not currently a curable disease, several disease-modifying
      therapies (DMTs) are now available, or are in development. These DMTs are all
      thought to primarily suppress autoimmune activity within the CNS. Each therapy
      has its own mechanism of action (MoA) and, as a consequence, each has a different
      efficacy and safety profile. Neurologists can now select therapies on a more
      individual, patient-tailored basis, with the aim of maximizing potential for long
      term efficacy without interruptions in treatment. The MoA and clinical profile of
      MS therapies are important considerations when making that choice or when
      switching therapies due to suboptimal disease response. This article therefore
      reviews the known and putative immunological MoAs alongside a summary of the
      clinical profile of therapies approved for relapsing forms of MS, and those in
      late-stage development, based on published data from pivotal randomized,
      controlled trials.

PMID- 24723128
TI  - Apoptotic enteropathy caused by antimetabolites and TNF-alpha antagonists.
AB  - AIMS: To investigate whether drugs others than mycophenolic acid and ipilimumab
      might cause graft-versus-host-like apoptotic enteropathy, the clinicopathological
      findings in four patients were examined who had developed watery diarrhoea and
      apoptotic enteropathy (three cases from colon and one case from ileal pouch)
      after intake of antimetabolites (methotrexate and capecitabine) and/or tumour
      necrosis factor-alpha inhibitors (etanercept and infliximab). METHODS: The
      clinical charts, endoscopy reports and intestinal biopsies from all endoscopies
      were reviewed for all patients. Biopsies were evaluated semiquantitatively for
      apoptosis of basal crypts, dilated damaged crypts, defined as cystically dilated
      crypts with flattened degenerated epithelium containing apoptotic debris and few
      neutrophils, and mucosal architecture. Further, the presence of intraepithelial
      lymphocytes, chronic inflammatory cells in the lamina propria and mucosal
      ulcerations was recorded and immunohistochemical analysis for human
      cytomegalovirus and herpes simplex virus was performed. RESULTS: Endoscopic
      examination revealed normal mucosa in two patients, whereas the other two showed
      focal ulcerations. Histological changes included increased apoptosis of basal
      crypts, the presence of dilated damaged crypts and architecture distortion. In
      all cases, a temporal association between drug intake and/or dose increase, and
      onset of diarrhoea, was observed, and no convincing evidence of other potentially
      underlying causes of colitis/enteritis was found, including infections.
      CONCLUSIONS: Pathologists should be aware of the expanding spectrum of drugs that
      can cause apoptotic enteropathy, including antimetabolites and tumour necrosis
      factor-alpha inhibitors.

PMID- 24723131
TI  - Ecological risk assessment of the uses of the organophosphorus insecticide
      chlorpyrifos, in the United States.

PMID- 24723129
TI  - Determinants of alpha-fetoprotein levels in patients with hepatocellular
      carcinoma: implications for its clinical use.
AB  - BACKGROUND: alpha-Fetoprotein (AFP) is a biomarker commonly used in the
      management of patients with hepatocellular carcinoma (HCC), although the possible
      determinants of its serum levels in these patients have not been adequately
      explored. For this study, the authors evaluated the relevance of demographic,
      clinical, and oncologic factors to the presence of elevated AFP levels in large
      cohort of patients with HCC. METHODS: In 4123 patients with HCC who were managed
      by the Italian Liver Cancer Group, AFP levels were assessed along with their
      association with demographic, biochemical, clinical, and oncologic
      characteristics. Patients were subdivided according to the presence of elevated
      AFP (ie, >10 ng/mL). RESULTS: AFP levels were elevated in 62.4% of patients with
      HCC. Multivariate logistic regression analysis indicated that being a woman (odds
      ratio [OR], 1.497; 95% confidence interval [95%CI], 1.250-1.793; P < .0001), the
      presence of cirrhosis (OR, 1.538; 95% CI, 1.050-2.254; P = .027), liver disease
      with viral etiology (OR, 1.900; 95% CI, 1.589-2.272; P < .0001), an elevated
      alanine aminotransferase level (OR, 1.878; 95% CI, 1.602-2.202; P < .0001), a low
      albumin level (OR, 1.301; 95% CI, 1.110-1.525; P = .012), an HCC tumor size >2 cm
      (OR, 1.346; 95% CI, 1.135-2.596; P = .001), multinodular HCC (OR, 1.641; 95% CI,
      1.403-1.920; P < .0001), and the presence of vascular invasion (OR, 1.774; 95%
      CI, 1.361-2.311; P < .0001) were associated independently with elevated levels of
      AFP. Both the median AFP level and the proportion of patients who had elevated
      levels increased with decreasing degrees of HCC differentiation (P < .0001).
      CONCLUSIONS: Sex and features of chronic liver disease were identified as
      nontumor characteristics that influence serum AFP levels in patients with HCC.
      These findings should be taken into account as limitations in interpreting the
      oncologic meaning of this biomarker in clinical practice.

PMID- 24723130
TI  - Translating the Diabetes Prevention Program into an Online Social Network:
      Validation against CDC Standards.
AB  - PURPOSE: The purpose of this study was to evaluate the efficacy of Prevent, an
      online social network-based translation of the Diabetes Prevention Program (DPP)
      lifestyle intervention, against the Centers for Disease Control and Prevention
      (CDC) Diabetes Prevention and Recognition Program (DPRP) outcome standards and
      weight loss outcomes of other DPP translations. METHODS: Two hundred twenty
      participants previously diagnosed with prediabetes were recruited online and
      enrolled in Prevent, a DPP-based group lifestyle intervention that integrates a
      private online social network, weekly lessons, health coaching, and a wireless
      scale and pedometer. Participants underwent a core 16-week intensive lifestyle
      change intervention and were then offered to continue with a post-core lifestyle
      change maintenance intervention, with the entire intervention (core plus post
      core) totaling 12 months. RESULTS: One hundred eighty-seven participants met
      inclusion criteria for the core program and achieved an average of 5.0% and 4.8%
      weight loss at 16 weeks and 12 months, respectively. They also had a 0.37%
      reduction in their A1C level at final measurement. One hundred forty-four of
      these same participants also met inclusion criteria for the post-core program and
      achieved an average of 5.4% and 5.2% weight loss at 16 weeks and 12 months,
      respectively, and a 0.40% reduction in A1C at final measurement. CONCLUSION:
      Results indicate that Prevent meets CDC DPRP outcome standards for diabetes
      prevention programs and performs favorably to other DPP translations. Considering
      national initiatives to address the obesity and diabetes epidemics, online
      delivery platforms like Prevent offer an effective and scalable solution.

PMID- 24723132
TI  - Properties and uses of chlorpyrifos in the United States.
AB  - Physical properties and use data provide the basis for estimating environmental
      exposures to chlorpyrifos (CPY) and for assessing its risks. The vapor pressure
      ofCPY is low, solubility in water is <1 mg L-1, and its log Kow is 5.
      Chlorpyrifos has short to moderate persistence in the environment as a result of
      several dissipation pathways that may proceed concurrently. Primary mechanisms of
      dissipation include volatilization, photolysis, abiotic hydrolysis, and microbial
      degradation.Volatilization dominates dissipation from foliage in the initial 12 h
      after application,but decreases as CPY adsorbs to foliage or soil. In the days
      after application, CPY adsorbs more strongly to soil, and penetrates more deeply
      into the soil matrix,becoming less available for volatilization. After the first
      12 h, other processes of degradation, such as chemical hydrolysis and catabolism
      by microbiota become important. The half-life of CPY in soils tested in the
      laboratory ranged from 2 toI ,575 d (N = 126) and is dependent on properties of
      the soil and rate of application.At application rates used historically for
      control of termites, the degradation rate is much slower than for agricultural
      uses. In agricultural soils under field conditions,half-lives are shorter (2 to
      120 d, N=58). The mean water-soil adsorption coefficient(Koc) of CPY is 8,216 mL
      g-1; negligible amounts enter plants via the roots,and it is not translocated in
      plants. Half-lives for hydrolysis in water are inversely dependent on pH, and
      range from 16 to 73 d. CPY is an inhibitor of acetylcholinesterase and is
      potentially toxic to most animals. Differences in susceptibility result from
      differences in rates of adsorption,distribution, metabolism, and excretion among
      species. CPY is an important tool in management of a large number of pests
      (mainly insects and mites) and is used on a wide range of crops in the U.S.
      Estimates of annual use in the U.S. from 2008 to 2012 range from 3.2 to 4.1 M kg
      y-1, which is about 50% less than the amount used prior to 2000. Applications to
      corn and soybeans accounts for 46-50%of CYP's annual use in the U.S.

PMID- 24723133
TI  - Fate in the environment and long-range atmospheric transport of the
      organophosphorus insecticide, chlorpyrifos and its oxon.
AB  - The fate and movement of the organophosphorus insecticide chlorpyrifos (CPY;CAS
      No.2921-88-2) and its metabolite chlorpyrifos-oxon (CPYO; CASNo.5598-15-2)
      determine exposures in terrestrial and aquatic environments.Detectable
      concentrations of the organophosphorus insecticide CPY in air, rain,snow and
      other environmental media have been measured in North America and other locations
      at considerable distances from likely agricultural sources, which indicates the
      potential for long range transport (LRT) in the atmosphere. This issue was
      addressed by first compiling monitoring results for CPY in all relevant
      environmental media. As a contribution to the risk assessment of CPY in remote
      regions, a simple mass balance model was developed to quantify likely
      concentrations at locations ranging from local sites of application to more
      remote locationsup to hundreds of km distant. Physical-chemical properties of CPY
      were reviewed and a set of consistent values for those properties that determine
      partitioning and reactivity were compiled and evaluated for use in the model. The
      model quantifies transformation and deposition processes and includes a tentative
      treatment of dispersion to lesser atmospheric concentrations. The model also
      addressed formation and fate of CPYO, which is the major transformation product
      of CPY. The Characteristic Travel Distance (CTD) at which 63% of the original
      mass of volatilized CPY is degraded or deposited-based on a conservative
      concentration of *OHradicals of 0.7 x 106 molecules cm-3 and a half-life of 3 h,
      was estimated to be 62 km. At lesser concentrations of *OH radical, such as
      occurs at night and at lesser temperatures, the CTD is proportionally greater. By
      including monitoring data from a variety of media, including air, rain, snow and
      biota, all monitored concentrations can be converted to the equilibrium criterion
      of fugacity, thus providing asynoptic assessment of concentrations of CPY and
      CPYO in multiple media. The calculated fugacities of CPY in air and other media
      decrease proportionally with increasing distance from sources, which can provide
      an approximate prediction of downwind concentrations and fugacities in media and
      can contribute to improved risk assessments for CPY and especially CPYO at
      locations remote from points of application, but still subject to LRT. The model
      yielded estimated concentrations that are generally consistent with
      concentrations measured, which suggests that the canonical fate and transport
      processes were included in the simulation model. The equations included in the
      model enable both masses and concentrations of CPY and CPYO to be estimated as a
      function of distance downwind following application.While the analysis provided
      here is useful and an improvement over previous estimates of LRT of CPY and CPYO,
      there is still need for improved estimates of the chemical-physical properties of
      CPYO.Based on the persistence in water, soils, and sediments, its
      bioconcentration and biomagnification in organisms, and its potential for long
      range transport, CPY and CPYO do not trigger the criteria for classification as a
      POP under the Stockholm convention or a PB chemical under EC 1107/2009.
      Nonetheless, CPY is toxic at concentrations less than the trigger for
      classification as T under EC 11 07 /2009; however,this simple trigger needs to be
      placed in the context of low risks to non-target organisms close to the areas of
      use. Overall, CPY and CPYO are judged to not trigger the PBT criteria of EC
      1107/2009.

PMID- 24723134
TI  - Exposures of aquatic organisms to the organophosphorus insecticide, chlorpyrifos
      resulting from use in the United States.
AB  - Concentrations of CPY in surface waters are an integral determinant of risk to
      aquatic organisms. CPY has been measured in surface waters of the U.S. in several
      environmental monitoring programs and these data were evaluated to characterize
      concentrations, in relation to major areas of use and changes to the label since
      2001, particularly the removal of domestic uses. Frequencies of detection and
      95th centile concentrations of CPY decreased more than fivefold between 1992 and
      2010. Detections in 1992-2001 ranged from 10.2 to 53%, while 2002-2010 detections
      ranged from 7 to 11%. The 95th centile concentrations ranged from 0.007 to 0.056
      j.lg L -I in 1992-2001 and 0.006-0.008 j.lg L -I in 2002-2010.The greatest
      frequency of detections occurred in samples from undeveloped and agricultural
      land-use classes. Samples from urban and mixed land-use classes had the smallest
      frequency of detections and 95th centile concentrations, consistent with the
      cessation of most homeowner uses in 2001. The active metabolite of CPY, CPYO, was
      not detected frequently or in large concentrations. In 10,375 analyses from
      several sampling programs conducted between 1999 and 2012, only 25 detections
      (0.24% of samples) of CPYO were reported and estimated concentrations were less
      than the LOQ.Although the monitoring data on CPY provide relevant insight in
      quantifying the range of concentrations in surface waters, few monitoring
      programs have sampled at a frequency sufficient to quantify the time-series
      pattern of exposure. Therefore,numerical simulations were used to characterize
      concentrations of CPY in water and sediment for three representative high
      exposure environments in the U.S. Thefate of CPY in the environment is dependent
      on a number of dissipation and degradation processes. In terms of surface waters,
      fate in soils is a major driver of the potential for runoff into surface waters
      and results from a number of dissipation studies in the laboratory were
      characterized. Aerobic degradation of CPY exhibits hi-phasic behavior in some
      soils; initial rates of degradation are greater than overal rates by factors of
      up to threefold. Along with fate in water, these data were considered in
      selecting parameters for the modeling concentrations in surface waters. An
      assessment of vulnerability to runoff was conducted to characterize the potential
      for CPY to be transported beyond a treated field in runoff water and eroded
      sediment across the conterminous U.S. A sensitivity analysis was performed on use
      practices of CPY to determine conditions that resulted in the highest potential
      runoff of CPY to aquatic systems to narrow the application practices and
      geographical areas of the country for selecting watersheds for detailed modeling.
      The selected focus-watersheds were Dry Creek in Georgia (production of pecans),
      Cedar Creekin Michigan (cherries), and Orestimba Creek in California (intensive
      agricultural uses). These watersheds provided realistic but reasonable worst-case
      predictions of concentrations of CPY in water and sediment.Estimated
      concentrations of CPY in water for the three watersheds were in general agreement
      with ambient monitoring data from 2002 to 20 I 0 in the datasets from US
      Geological Survey (USGS), California Department of Pesticide Regulation(CDPR),
      and Washington State Department of Ecology (WDOE). Maximum daily concentrations
      predicted for the watershed in California, Georgia, and Michigan were 3.2, 0.04
      I, and 0.073 Jlg L -I, respectively, with the 28-d aerobic soil metabolism half
      life and 4.5, 0.042, and 0. I 22 Jlg L - 1, respectively, with the 96-d soil
      halflife.These estimated values compared favorably with maximum concentrations
      measured in surface water, which ranged from 0.33 to 3.96 Jlg L -1* For
      sediments,the maximum daily concentrations predicted for the watersheds in
      California,Georgia, and Michigan were I 1.2, 0.077, and 0.058 Jlg kg-1,
      respectively, with the 28-d half-life and 22.8, 0.080, and 0.087 Jlg kg-1,
      respectively, with the 96-d soil half-life. CYP was detected in 12 samples (I 0%)
      out of 123 sample analyses that existed in the USGS, CDPR, and WDOE databases.
      The concentrations reported in these detections were from <2.0, up to 19 Jlg kg-
      1, with the exception of one value reported at 58.6 Jlg kg- 1* Again, the modeled
      values compared favorably with these measured values. Duration and recovery
      intervals between toxicity threshold concentrations of 0.1 and 1.0 Jlg L - 1 were
      also computed. Based on modeling with the half-life of 28 d, no exceedance events
      were identified in the focus watersheds in Georgia or Michigan. Using the half
      life of 96 d, only three events of 1-d duration only were identified in the
      Michigan focus-watershed. Frequency of exceedancc was greater in the California
      focus watershed, though the median duration was only I -d.

PMID- 24723135
TI  - Risks to aquatic organisms from use of chlorpyrifos in the United States.
AB  - The risk of chlorpyrifos (CPY) to aquatic organisms in surface water of North
      America was assessed using measured concentrations in surface waters and modeling
      of exposures to provide daily concentrations that better characterize peak
      exposures.Ecological effects were compared with results of standard laboratory
      toxicity tests with single species as well as microcosm and mesocosm studies
      comprised of complex aquatic communities. The upper 90th centile 96-h
      concentrations(annual maxima) of chlorpyrifos in small streams in agricultural
      watersheds in Michigan and Georgia were estimated to be :-:;0.02 llg L-1; in a
      reasonable worstcase California watershed, the 90th centile 96-h annual maximum
      concentrations ranged from 1.32 to 1.54 llg L - 1* Measured concentrations of
      chlorpyrifos are less than estimates from simulation models. The 95th centile for
      more than I 0,000 records compiled by the US Geological Survey was 0.008 llg L 
      1* Acute toxicity endpoints for 23 species of crustaceans ranged from 0.035 to
      457 llg L -I; for 18 species of aquatic insects, from 0.05 to 27 llg L -I; and
      for 25 species of fish, from 0.53to >806 llg L -I. The No Observed Adverse Effect
      Concentration (NOAECeco) in more than a dozen microcosm and mesocosm studies
      conducted in a variety of climatic zones, was consistently 0.1 llg L -1* These
      results indicated that concentrations of CPY in surface waters are rarely great
      enough to cause acute toxicity to even the most sensitive aquatic species. This
      conclusion is consistent with the lack of fish kills reported for CPY's normal
      use in agriculture in the U.S.Analysis of measured exposures showed that
      concentrations in surface waters declined after labeled use-patterns changed in
      2001, and resulted in decreased risks for crustaceans, aquatic stages of insects,
      and fish. Probabilistic analysis of 96-h time-weighted mean concentrations,
      predicted by use of model simulation for three focus-scenarios selected for
      regions of more intense use of CPY and vulnerability to runoff, showed that risks
      from individual and repeated exposures to CPY in the Georgia and Michigan
      watersheds were de minimis. Risks from individual exposures in the intense-use
      scenario from California were de minimis for fish and insects and low for
      crustaceans. Risks from repeated exposures in the Californiain tense-use scenario
      were judged not to be ecologically relevant for insects and fish,but there were
      some risks to crustaceans. Limited data show that chlorpyrifos oxon(CPYO), the
      active metabolite of CPY is of similar toxicity to the parent
      compound.Concentrations of CPYO in surface waters are smaller than those of CPY
      and less frequently detected. Risks for CPYO in aquatic organisms were judged to
      be deminimis.Several uncertainties common to all AChE inhibitors were identified.
      Insufficient data were available to allow interpretation of the relevance of
      effects of CPY (and other pesticides that also target AChE) on behavior to
      assessment endpoints such as survival, growth, development, and reproduction.
      Data on the recovery of AChE from inhibition by CPY in fish are limited. Such
      data are relevant to the characterization of risks from repeated exposures, and
      represent an uncertainty in the assessment of risks for CPY and other pesticides
      that share the same target and toxico dynamics. More intensive monitoring of
      areas of greater use and more comprehensive models of cumulative effects that
      include rates of accumulation, metabolism and recovery of AChE in the more
      sensitive species would be useful in reducing this uncertainty.

PMID- 24723136
TI  - Refined avian risk assessment for chlorpyrifos in the United States.
AB  - Refined risk assessments for birds exposed to flowable and granular formulations
      ofCPY were conducted for a range of current use patterns in the United States.
      Overall,the collective evidence from the modeling and field study lines of
      evidence indicate that flowable and granular CPY do not pose significant risks to
      the bird communities foraging in agro-ecosystems in the United States. The
      available information indicates that avian incidents resulting from the legal,
      registered uses of CPY have been very infrequent since 2002 (see SI Appendix 3).
      The small number of recent incidents suggests that the current labels for CPY are
      generally protective of birds.However, incident data are uncertain because of the
      difficulties associated with finding dead birds in the field and linking any
      mortality observed to CPY.Plowable CPY is registered for a variety of crops in
      the United States including alfalfa, brassica vegetables, citrus, corn, cotton,
      grape, mint, onion, peanut, pome and stone fruits, soybean, sugar beet,
      sunflower, sweet potato, tree nuts, and wheat under the trade name Lorsban
      Advanced. The major routes of exposure for birds to flowable CPY were consumption
      of treated dietary items and drinking water. The Liquid Pesticide Avian Risk
      Assessment Model (Liquid PARAM) was used to simulate avian ingestion of CPY by
      these routes of exposure. For acute exposure,Liquid PARAM estimated the maximum
      retained dose in each of 20 birds on each of1,000 fields that were treated with
      CPY over the 60-d period following initial application.The model used a 1-h time
      step. For species lacking acceptable acute oral toxicity data (all focal species
      except northern bobwhite (C. virginianus) and redwinged blackbird (A.
      phoeniceus)), a species sensitivity distribution (SSD) approach was used to
      generate hypothetical dose-response curves assuming high, median and low
      sensitivity to CPY. For acute risk, risk curves were generated for each use
      pattern and exposure scenario. The risk curves show the relationship between
      exceedence probability and percent mortality. The results of the Liquid PARAM
      modeling exercise indicate that flow able CPY poses an acute risk to some bird
      species, particularly those species that are highly sensitive and that forage
      extensively in crops with high maximum application rates (e.g., grapefruit,
      orange). Overall, most bird species would not experience significant mortality as
      a result of exposure to flowable CPY.The results of a number of field studies
      conducted at application rates comparable to those on the Lorsban Advanced label
      indicate that flowable CPY rarely causes avian mortality. The results of the
      field studies suggest that Liquid PARAM is likely over-estimating acute risk to
      birds for flowable CPY.For chronic exposure, Liquid PARAM estimated the maximum
      total daily intake (TDI) over a user-specified exposure duration (28-d in the
      case of CPY).The maximum average TDI was compared to the chronic NOEL and LOEL
      from the most sensitive species tested for CPY, the mallard. This comparison was
      done for each of the 20 birds in each of the 1000 fields simulated in Liquid
      PARAM.The outpu. ~ are estimates of the probabilities of exceeding the NOEL and
      LOEL.Liquid PAkAM did not predict significant adverse effects resulting from
      chronic exposure to flowable CPY. The small number of incidents (2) involving CPY
      reported since 2002 suggests that the current labels for CPY are generally
      protective of birds.Granular CPY is registered for a wide variety of crops
      including brassica vegetables, corn, onion, peanut, sugar beet, sunflower, and
      tobacco under the trade name Lorsban 15G. Consumption of grit is required by many
      birds to aid in digestion of hard dietary items such as seeds and insects.
      Because CPY granules are in the same size range as natural grit particles
      consumed by birds, there is a potential for birds to mistakenly ingest granular
      CPY instead of natural grit. We developed the Granular Pesticide Avian Risk Model
      (GranPARAM) to simulate grit ingestion behavior by birds. The model accounts for
      proportion of time that birds forage for grit in treated fields, relative
      proportions of natural grit versus pesticide granules onthe surface of treated
      fields, rates of ingestion of grit, attractiveness of pesticide granules relative
      to natural grit and so on. For CPY, each model simulation included20 birds on
      each of 1,000 fields to capture variability in rates of ingestion of grit and for
      aging behavior between birds within a focal species, and variability in soil
      composition between fields for the selected use pattern. The estimated dose for
      each birdwas compared with randomly chosen doses from relevant dose-response
      curves forCPY. Our analysis for a wide variety of use patterns on the Lorsban 15G
      label found that granular CPY poses little risk of causing mortality to bird
      species that frequent treated fields immediately after application. The
      predictions of the model have been confirmed in several avian field studies
      conducted with Lorsban 15G at application rates similar to or exceeding maximum
      application rates on the Lorsban 15G label.

PMID- 24723137
TI  - Risk to pollinators from the use of chlorpyrifos in the United States.
AB  - CPY is an organophosphorus insecticide that is widely used in North American
      agriculture. It is non-systemic, comes in several sprayable and granular
      formulations,and is used on a number of high-acreage crops on which pollinators
      can forage,including tree fruits, alfalfa, corn, sunflower, and almonds. Bees
      (Apoidea) are the most important pollinators of agricultural crops in North
      America and were the main pollinators of interest in this risk assessment.The
      conceptual model identified a number of potential exposure pathways for
      pollinators, some more significant than others. CPY is classified as being highly
      toxic to honey bees by direct contact exposure. However, label precautions and
      good agricultural practices prohibit application of CPY when bees are flying
      and/or when flowering crops or weeds are present in the treatment area.
      Therefore, the risk of CPY to pollinators through direct contact exposure should
      be small. The main hazards for primary exposure for honey bees are dietary and
      contact exposure from flowers that were sprayed during application and remain
      available to bees after application. The main pathways for potential secondary
      exposure to CPY is through pollen and nectar brought to the hive by forager bees
      and the sublethal body burden of CPY carried on forager bees. Foraging for other
      materials, including water or propolis, does not appear to be an important
      exposure route. Since adult forager honey bees are most exposed, their protection
      from exposure via pollen, honey, and contact with plant surfaces is expected to
      be protective of other life stages and castes of honey bees.Tier- I approaches to
      estimate oral exposure to CPY through pollen and nectar/honey, the principle food
      sources for honey bees, suggested that CPY poses a risk to honey bees through
      consumption of pollen and nectar. However, a Tier-2 assessment of concentrations
      reported in pollen and honey from monitoring work in North America indicated
      there is little risk of acute toxicity from CPY through consumption of these food
      sources.Several models were also used to estimate upper-limit exposure of honey
      bees to CPY through consumption of water from puddles or dew. All models suggest
      that the risk of CPY is below the LOC for this pathway. Laboratory experiments
      with field-treated foliage, and semi-field and field tests with honey bees,
      bumble bees,and alfalfa leaf cutting bees indicate that exposure to foliage,
      pollen and/or nectar is hazardous to bees up to 3 d after application of CPY to a
      crop. Pollinators exposed to foliage, pollen or nectar after this time should be
      minimally affected.Several data gaps and areas of uncertainty were identified,
      which apply to CPYand other foliar insecticides. These primarily concern the lack
      of exposure and toxicological data on non-Apis pollinators. Overall, the rarity
      of reported bee kill incidents involving CPY indicates that compliance with the
      label precautions and good agricultural practice with the product is the norm in
      North American agriculture.Overall, we concluded that, provided label directions
      and good agricultural practices are followed, the use of CPY in agriculture in
      North America does not present an unacceptable risk to honeybees.

PMID- 24723138
TI  - RNAi silencing of the SoxE gene suppresses cell proliferation in silkworm BmN4
      cells.
AB  - The transcription factor SoxE is mainly expressed in the gonad and involved in
      the regulation of gonad development and sex determination in animals. Here, we
      used the silkworm ovary-derived BmN4-SID1 cell line to survey the roles of the
      silkworm SoxE protein (BmSoxE) and predict its candidate binding targets. RNAi
      mediated silencing of BmSoxE expression suppressed cell proliferation in BmN4
      SID1 cells. A further cell cycle analysis revealed that this inhibition of cell
      proliferation was largely due to cell cycle arrest in G1 phase when BmSoxE
      expression was blocked in BmN4-SID1 cells. Genome-wide microarray expression
      analyses demonstrated that the expression levels of a set of genes were
      significantly altered following BmSoxE RNAi. More than half of these genes
      contained conserved binding sites for HMG box domain of the Sox proteins and were
      predicted to be candidate binding targets for BmSoxE. Importantly, some of the
      candidate targets may be associated with the effect of BmSoxE on cell
      proliferation. Several candidate target genes showed gonad-specific expression in
      silkworm larvae. Taken together, these data demonstrate that BmSoxE is required
      for cell proliferation in silkworm BmN4-SID1 cells and provide valuable
      information for further investigations of the molecular control exerted by the
      BmSoxE protein over cell proliferation and gonad development in the silkworm. 

PMID- 24723139
TI  - Replication of Mycobacterium tuberculosis in retinal pigment epithelium.
AB  - IMPORTANCE: Mycobacterium tuberculosis is an important cause of posterior uveitis
      in tuberculosis-endemic regions. Clinical and histopathologic evidence suggests
      that retinal pigment epithelium (RPE) can harbor M tuberculosis. However, the
      mechanism of M tuberculosis phagocytosis and its growth in RPE is not clear.
      OBJECTIVE: To investigate M tuberculosis phagocytosis, replication, and
      cytopathic effects in RPE cells compared with macrophages. DESIGN, SETTING, AND
      PARTICIPANTS: Human fetal RPE and monocytic leukemia macrophage (THP-1) cell
      lines were cultured, and RPE and THP-1 cells were exposed to avirulent M
      tuberculosis H37Ra. Mycobacteria were added to RPE and THP-1 cells with a 5:1
      multiplicity of infection. Nonphagocytized M tuberculosis was removed after 12
      hours of exposure (day 0). Cells were harvested at days 0, 1, and 5 to count live
      and dead cells and intracellular mycobacteria. Toll-like receptor 2 (TLR2) and
      TLR4 expression was determined by immunohistochemistry; intracellular bacillary
      load, following TLR2 and TLR4 blockade. MAIN OUTCOMES AND MEASURES: Number of
      intracellular M tuberculosis, cell survival, and TLR2 and TLR4 expression in RPE
      and THP-1 cells following exposure to M tuberculosis. RESULTS: At day 0, an equal
      number of intracellular M tuberculosis was observed per THP-1 and RPE cells (0.45
      and 0.35 M tuberculosis per RPE and THP-1 cells, respectively). Mean (SD) number
      of intracellular M tuberculosis at day 5 was 1.9 (0.03) and 3.3 (0.01) per RPE
      and THP-1 cells, respectively (P < .001). Viability of infected RPE was
      significantly greater than that of THP-1 cells at day 5 (viable cells: 17 [8%]
      THP-1 vs 73% [4%] RPE; P < .05). Expression of TLR2 and TLR4 was detected in both
      cell types after 12 hours of exposure. Inhibition of TLR2 and TLR4 reduced
      intracellular M tuberculosis counts in RPE but not in THP-1 cells. CONCLUSIONS
      AND RELEVANCE: Mycobacterium tuberculosis is phagocytized by RPE to a similar
      extent as in macrophages. However, RPE cells are better able to control bacillary
      growth and RPE cell survival is greater than that of THP-1 cells following
      mycobacterial infection, suggesting that RPE can serve as a reservoir for
      intraocular M tuberculosis infection.

PMID- 24723140
TI  - Genome-based prediction of maize hybrid performance across genetic groups,
      testers, locations, and years.
AB  - KEY MESSAGE: The calibration data for genomic prediction should represent the
      full genetic spectrum of a breeding program. Data heterogeneity is minimized by
      connecting data sources through highly related test units. One of the major
      challenges of genome-enabled prediction in plant breeding lies in the optimum
      design of the population employed in model training. With highly interconnected
      breeding cycles staggered in time the choice of data for model training is not
      straightforward. We used cross-validation and independent validation to assess
      the performance of genome-based prediction within and across genetic groups,
      testers, locations, and years. The study comprised data for 1,073 and 857 doubled
      haploid lines evaluated as testcrosses in 2 years. Testcrosses were phenotyped
      for grain dry matter yield and content and genotyped with 56,110 single
      nucleotide polymorphism markers. Predictive abilities strongly depended on the
      relatedness of the doubled haploid lines from the estimation set with those on
      which prediction accuracy was assessed. For scenarios with strong population
      heterogeneity it was advantageous to perform predictions within a priori defined
      genetic groups until higher connectivity through related test units was achieved.
      Differences between group means had a strong effect on predictive abilities
      obtained with both cross-validation and independent validation. Predictive
      abilities across subsequent cycles of selection and years were only slightly
      reduced compared to predictive abilities obtained with cross-validation within
      the same year. We conclude that the optimum data set for model training in genome
      enabled prediction should represent the full genetic and environmental spectrum
      of the respective breeding program. Data heterogeneity can be reduced by
      experimental designs that maximize the connectivity between data sources by
      common or highly related test units.

PMID- 24723141
TI  - Hospital costs of total hip arthroplasty for developmental dysplasia of the hip.
AB  - BACKGROUND: Developmental dysplasia of the hip (DDH) is a leading cause of total
      hip arthroplasty (THA) in younger patients. It is unknown how the hospital costs
      of THA in patients with DDH compare with patients with degenerative arthritis.
      QUESTIONS/PURPOSES: We undertook this study to determine (1) the hospital cost
      and length of stay associated with primary THA in patients with dysplasia
      compared with nondysplastic control subjects; (2) the hospital cost and length of
      stay of THA in severely dysplastic hips compared with mildly dysplastic hips; and
      (3) perioperative complications in patients with DDH compared with patients
      without dysplasia. METHODS: This matched-cohort study included 354 patients
      undergoing primary THA for DDH and 1029 age-, sex-, and calendar year-matched
      patients undergoing THA for primary osteoarthritis between 2000 and 2008. DDH
      severity was measured by the Crowe classification. An institutional database was
      used to calculate the cost of care. Using line item details (date, type,
      frequency, and billed charge) for every procedure or service billed at our
      institution for each patient, bottom-up microcosting valuation techniques were
      used to generate standardized inflation-adjusted estimates of the cost of each
      service or procedure in constant dollars. Generalized linear random effects
      models were used to compare length of stay and costs during hospitalization and
      the 90-day period after surgery. Query of a longitudinal institutional database
      was used to identify documented complications. RESULTS: Patients with DDH
      undergoing primary THA incurred higher hospital costs than patients with primary
      osteoarthritis (USD 16,949 versus USD 16,485, p = 0.012). Operating room costs
      (USD 3471 versus USD 3417, p = 0.0085) and implant costs (USD 3896 versus USD
      3493, p < 0.001) were higher in the DDH group compared with the osteoarthritis
      group. Length of stay was not different between the two groups (4 versus 4 days,
      p = 0.46). Crowe 4 hips had higher hospital costs than Crowe 1 hips (USD 21,246
      versus USD 16,345, p < 0.001) with an associated longer length of stay (5 days
      versus 4 days, p = 0.0011) and higher implant costs (USD 4380 versus USD 3788, p
      = 0.0012). There was no detectible difference in 90-day complications in the case
      group compared with patients undergoing THA for osteoarthritis. CONCLUSIONS:
      Hospital cost of primary THA is approximately USD 450 higher in patients with DDH
      compared with osteoarthritis. Increased severity of dysplasia (Crowe
      classification) was associated with higher costs. LEVEL OF EVIDENCE: Level IV,
      economic and decision analyses. See Guidelines for Authors for a complete
      description of levels of evidence.

PMID- 24723143
TI  - The sports bra, the ACL, and Title IX--the game in play.

PMID- 24723142
TI  - Does targeted nerve implantation reduce neuroma pain in amputees?
AB  - BACKGROUND: Symptomatic neuroma occurs in 13% to 32% of amputees, causing pain
      and limiting or preventing the use of prosthetic devices. Targeted nerve
      implantation (TNI) is a procedure that seeks to prevent or treat neuroma-related
      pain in amputees by implanting the proximal amputated nerve stump onto a
      surgically denervated portion of a nearby muscle at a secondary motor point so
      that regenerating axons might arborize into the intramuscular motor nerve
      branches rather than form a neuroma. However, the efficacy of this approach has
      not been demonstrated. QUESTIONS/PURPOSES: We asked: Does TNI (1) prevent primary
      neuroma-related pain in the setting of acute traumatic amputation and (2) reduce
      established neuroma pain in upper- and lower-extremity amputees? METHODS: We
      retrospectively reviewed two groups of patients treated by one surgeon: (1) 12
      patients who underwent primary TNI for neuroma prevention at the time of acute
      amputation and (2) 23 patients with established neuromas who underwent neuroma
      excision with secondary TNI. The primary outcome was the presence or absence of
      palpation-induced neuroma pain at last followup, based on a review of medical
      records. The patients presented here represent 71% of those who underwent primary
      TNI (12 of 17) and 79% of those who underwent neuroma excision with secondary TNI
      (23 of 29 patients) during the period in question; the others were lost to
      followup. Minimum followup was 8 months (mean, 22 months; range, 8-60 months) for
      the primary TNI group and 4 months (mean, 22 months; range, 4-72 months) for the
      secondary TNI group. RESULTS: At last followup, 11 of 12 patients (92%) after
      primary TNI and 20 of 23 patients (87%) after secondary TNI were free of
      palpation-induced neuroma pain. CONCLUSIONS: TNI performed either primarily at
      the time of acute amputation or secondarily for the treatment of established
      symptomatic neuroma is associated with a low frequency of neuroma-related pain.
      By providing a distal target for regenerating axons, TNI may offer an effective
      strategy for the prevention and treatment of neuroma pain in amputees.

PMID- 24723144
TI  - Convenient purification of gold clusters by co-precipitation for improved sensing
      of hydrogen peroxide, mercury ions and pesticides.
AB  - An effective separation process is developed to remove free protein from the
      protein-protected gold clusters via co-precipitation with zinc hydroxide on their
      surface. After dialysis, the purified clusters exhibit an enhanced fluorescence
      for improved sensitive detection and selective visualization. 

PMID- 24723145
TI  - The various architectures and properties of a series of coordination polymers
      tuned by the central metals.
AB  - Five new metal-organic coordination polymers based on the mixed ligands of a semi
      rigid bis-pyridyl-bis-amide N,N'-bis(3-pyridinecarboxamide)-1,2-cyclohexane (3
      bpah) and 1,4-benzenedicarboxylic acid (1,4-H2BDC), namely [Co(3-bpah)(1,4
      BDC)(H2O)3] (1), [Ni(3-bpah)(1,4-BDC)(H2O)3] (2), [Cu(3-bpah)(1,4-BDC)] (3),
      [Zn(3-bpah)(1,4-BDC)].H2O (4) and [Cd(3-bpah)(1,4-BDC)(H2O)] (5), have been
      hydrothermally synthesized and structurally characterized. Complexes 1 and 2 are
      isostructural and display the similar 1D infinite chains, which are further
      linked via hydrogen-bonding interactions to generate 3D supramolecular
      frameworks. Complex 3 features a 3D polymeric framework with CdSO4-like topology.
      Complexes 4 and 5 show two similar 2D (2,4)-connected networks with (4.8(5))(4)
      topology, in which the 3-bpah ligands adopt different MU2-bridging coordination
      modes via the ligation of two pyridyl nitrogen atoms in 4 and via the ligation of
      one pyridyl nitrogen and one amide oxygen atom in 5. In addition, the central
      metals show different coordination geometries in 4 and 5. The adjacent layers of
      complexes 4 and 5 are finally extended into 3D supramolecular architectures
      through hydrogen-bonding interactions. The effects of the central metals on the
      structures and properties of complexes 1-5 have been discussed. The
      electrochemical properties of complexes 1-3 and fluorescent sensing behaviors of
      4-5 toward ethanol and nitrobenzene have been investigated in detail. 

PMID- 24723146
TI  - Flavonoid profile of Lupinus mexicanus germinated seed extract and evaluation of
      its neuroprotective effect.
AB  - The aim of this study was to determine the flavonoid profile of Lupinus mexicanus
      germinated seed extract (PE) and to evaluate its effect as a phytoestrogen on the
      morphometric parameters of CA3 hippocampal neurons of ovariectomized rats (OVX).
      L. mexicanus seeds, germinated for 48 h, were homogenized and macerated using an
      80% ethanol solution. The extract was analyzed by HPLC/MS-MS. Thirty young Wistar
      strain female rats (200+/-10 g) were randomly distributed into four groups: sham
      operated (S) treated with dimethyl sulfoxide (vehicle); ovariectomized and
      treated with 1250 MUg of PE extract (OVX-PE); ovariectomized and treated with 5
      MUg estradiol benzoate (OVX-EB); and ovariectomized and vehicle treated (OVX).
      All substances were injected subcutaneously daily for 28 days. On day 29, the
      animals were sacrificed, perfused, and fixed to obtain the brains for
      histological processing. Each brain was cut and stained with hematoxylin and
      eosin. The thickness of the stratum oriens (SO), the nuclear diameter, and the
      neuronal density were measured in the hippocampus CA3 area. Nine different
      flavonoids and one non-identified compound were detected. The histological
      analysis demonstrated that the thickness of the SO was higher in the OVX-EB and S
      groups than in the OVX-PE and OVX groups (p?0.05); in addition, the nuclear
      diameters of the neurons in the OVX-EB and S groups were higher compared with the
      other groups (p?0.05). The OVX group had the highest cellular density among
      groups (p?0.05). Based on our results, the PE obtained did not have beneficial
      effects on CA3 hippocampal neurons.

PMID- 24723147
TI  - Effect of rivastigmine on mobility of patients with higher-level gait disorder: a
      pilot exploratory study.
AB  - BACKGROUND: Higher-level gait disorder (HLGD) in older adults is characterized by
      postural instability, stepping dysrhythmicity, recurrent falls and progressive
      immobility. Cognitive impairments are frequently associated with HLGD.
      OBJECTIVES: The aim of this study was to compare gait and cognitive performance
      before and after the use of rivastigmine in patients with HLGD, free from
      cognitive impairment or Parkinsonism. METHODS: Fifteen non-demented patients with
      HLGD (age 79.2 +/- 5.9 years; 11 women; Mini-Mental State Examination [MMSE] 28.3
      +/- 1.4) received escalating doses of rivastigmine for 12 weeks in an open-label,
      pilot study. They were assessed before and after treatment (week 0 and week 12),
      and after a 4-week washout period (week 16). Assessments included the Mindstreams
      computerized neuropsychological battery, Activities-specific Balance Confidence
      Scale, State-Trait Anxiety Inventory, Geriatric Depression Scale, Timed Up and Go
      (TUG) test, gait speed and stride time variability. One-way multiple analysis of
      variance tests for repeated measures were used, and Pillai's trace test was
      considered as robust to investigate significant differences. RESULTS: The mean
      dose of rivastigmine during the 8-12 week period was 5.1 +/- 2.3 mg/day. A
      positive effect was observed on the Mindstreams memory subscale and anxiety
      scores [Pillai's trace: F(6,724) = 0.508, p = 0.010; and F(7,792) = 0.545, p =
      0.006, respectively, over the course of the study] as well as on mobility (TUG
      test) [Pillai's trace: F(4,863) = 0.448; p = 0.028], whereas gait speed and
      stride time variability did not change. CONCLUSIONS: The use of relatively low
      dose rivastigmine did not affect gait speed and stride time variability; however,
      the general mobility and anxiety were improved. These preliminary results warrant
      a larger, randomized, placebo-controlled study.

PMID- 24723148
TI  - Differential effects of commercial-grade and purified poloxamer 188 on renal
      function.
AB  - Poloxamer 188 (P188) is a non-ionic amphiphilic copolymer with hemorheologic,
      antithrombotic, anti-inflammatory, and cytoprotective properties. It potentially
      has clinical utility in diverse diseases, such as acute myocardial infarction,
      acute limb ischemia, shock, acute stroke, heart failure, and sickle cell crisis.
      P188 is available as an excipient-grade product, manufactured to National
      Formulary specifications, which we refer to as P188-NF. During synthesis of P188
      NF, polymerization of its polyoxyethylene and polyoxypropylene components
      generates undesirable low molecular weight (LMW) substances, such as truncated
      polymers and glycols. In early clinical studies, P188-NF yielded unexpected renal
      dysfunction. Here, we explore the nature of the renal dysfunction associated with
      P188-NF and use a purified (more homogenous) form of P188-NF (P188-P) to show
      that removal of LMW substances is associated with substantially less renal
      dysfunction. In both a remnant-kidney animal model and in clinical studies, P188
      P demonstrates a substantially improved renal safety profile. 

PMID- 24723149
TI  - A novel cluster of mariner-like elements belonging to mellifera subfamily from
      spiders and insects: implications of recent horizontal transfer on the South-West
      Islands of Japan.
AB  - Mariner-like elements (MLEs) have been isolated from various eukaryotic genomes
      and they are divided into 15 subfamilies, including main five subfamilies:
      mauritiana, cecropia, mellifera/capitata, irritans, and elegans/briggsae. In the
      present study, MLEs belonging to mellifera subfamily were isolated from various
      spiders and insects (Hymenoptera and Lepidoptera) inhabiting the South-West
      Islands of Japan and neighboring regions. MLEs isolated from 15 different species
      formed a distinct novel cluster in mellifera subfamily. MLEs obtained from three
      different species [i.e., the bee Amegilla senahai subflavescens (Amsmar1), the
      wasp Campsomeris sp. (Casmar1), and the swallowtail butterfly Pachliopta
      aristolochiae (Paamar1)] contained an intact open reading frame that encoded a
      putative transposase. These transposases exhibited high similarity of 97.9% among
      themselves. In case of Casmar1, the presence of an intact ORF was found in high
      frequencies (i.e., 11 out of 12 clones). In addition, these transposases also
      showed the presence of a terminal inverted repeat-binding motif, DD(34)D and two
      highly conserved amino acid motifs, (W/L)(I/L)PHQL and YSP(D/N)L(A/S)P. These two
      motifs differed from previously known motifs, WVPHEL and YSPDLAP. MLEs isolated
      from these three different species may have been inserted into their genomes by
      horizontal transfer. Furthermore, the presence of an intact ORF suggests that
      they are still active in habitats along these isolated islands.

PMID- 24723150
TI  - Multidimensional scaling analysis identifies pathological and prognostically
      relevant profiles of circulating T-cells in chronic lymphocytic leukemia.
AB  - Antitumor immunity in chronic lymphocytic leukemia (CLL) is hampered by highly
      dysfunctional T-cells. Although certain T-cell subsets have been reported to be
      of prognostic significance in this disease, their interplay is complex and it
      remains incompletely understood which of these subsets significantly drive CLL
      progression. Here, we determined immunological profiles of 24 circulating T-cell
      subsets from 79 untreated individuals by multiparametric flow cytometry. This
      screening cohort included healthy donors, patients with monoclonal B-cell
      lymphocytosis (MBL), Rai 0 CLL and advanced CLL. We applied multidimensional
      scaling analysis as rigorous and unbiased statistical tool to globally assess the
      composition of the circulating T-cell environment and to generate T-cell scores
      reflecting its integrity. These scores allowed clear distinction between advanced
      CLL and healthy controls, whereas both MBL and Rai 0 CLL showed intermediate
      scores mirroring the biological continuum of CLL and its precursor stages. T-cell
      stimulation and suppression assays as well as longitudinal T-cell profiling
      showed an increasingly suppressive regulatory function initiating at the MBL
      stage. Effector function was impaired only after transition to CLL and partially
      recovered after chemoimmunotherapy. In an independent validation cohort of 52
      untreated CLL cases, aberrant T-cell profiles were significantly associated with
      shorter time to treatment independently of other prognostic parameters. Random
      forest modeling predicted regulatory T-cell, gamma/delta and NKT-cells, as well
      as exhaustion of the CD8+ subset as potential drivers of progression. Our data
      illustrate a pathological T-cell environment in MBL that evolves toward a more
      and more suppressive and prognostically relevant profile across the disease
      stages. 

PMID- 24723152
TI  - Regioselective 1,4- over 1,2-addition of 3,3-bis(silyl) allyloxy lithium to
      enals, enones and enoates. The remarkable alpha-effect of silicon.
AB  - A remarkable alpha-effect of silicon has been discovered that results in soft
      nucleophilicity at the Cgamma of 3,3-bis(silyl) allyloxy lithium 1. The addition
      of 1 to alpha,beta-unsaturated carbonyl compounds, including enals, proceeds in a
      1,4- over 1,2-manner with medium to good regioselectivity, whereas the parent
      allyloxy lithium 4 undergoes complete 1,2-addition. The results from DFT
      calculations of HMPAcomplexed 1 and 4 provide the rationale to explain this
      different regioselectivity.

PMID- 24723151
TI  - CT-guided implantation of radioactive 125I seed in advanced non-small-cell lung
      cancer after failure of first-line chemotherapy.
AB  - PURPOSE: We investigated implanting computed tomography (CT)-guided (125)I seed
      to treat locally advanced non-small-cell lung cancer (NSCLC) after chemotherapy
      failure. METHODS: From January 2005 to July 2010, we recruited 69 patients with
      locally advanced NSCLC who had each had first-line chemotherapy four to six times
      but had progressive disease; 34 received (125)I seed implantation with second
      line chemotherapy (Group A) and 35 received second-line chemotherapy only (Group
      B). RESULTS: Mean follow-up was 32 months (range 5-56 months). Overall 2-year
      local control rate for existing lung lesions was Group A: 39.9 %; Group B: 12.5 %
      (P < 0.05). The 1-, 3-year, and median overall survival was 68.7 and 20.8 % at
      17.4 months in Group A; and 45.1 and 18.7 % at 11.3 months in Group B,
      respectively (P > 0.05). Local 3-, 24-month, and median progression-free survival
      was Group A: 100 and 79.1 % at 11 months; Group B: 76.5 and 18.7 % at 7.3 months,
      respectively. The groups did not significantly differ in treatment toxicity.
      Chest pain remission was Group A: 82.1 % (23/28); Group B: 30.8 % (8/26) (P <
      0.05). Group A showed no radiation-related pneumonia, esophagitis, bronchial
      fistulae, or life-threatening morbidity. CONCLUSION: CT-guided radioactive seed
      (125)I implantation procedure is safe and well tolerated in treating locally
      advanced NSCLC, with few complications. It has good local control rate and can
      relieve symptoms without increasing side effects.

PMID- 24723153
TI  - Adjustable nasal transposition of split lateral rectus muscle for third nerve
      palsy.
AB  - IMPORTANCE: Third nerve palsy causes disfiguring, incomitant strabismus with
      limited options for correction. OBJECTIVE: To evaluate the oculomotor outcomes,
      anatomical changes, and complications associated with adjustable nasal
      transposition of the split lateral rectus (LR) muscle, a novel technique for
      managing strabismus associated with third nerve palsy. DESIGN, SETTING, AND
      PARTICIPANTS: Retrospective medical record review appraising outcomes of 6
      consecutive patients with third nerve palsy who underwent adjustable nasal
      transposition of the split LR muscle between 2010 and 2012 with follow-up of 5 to
      25 months at a tertiary referral center. INTERVENTION: Adjustable nasal
      transposition of the split LR muscle. MAIN OUTCOMES AND MEASURES: The primary
      outcome was postoperative horizontal and vertical alignment. Secondary outcomes
      were (1) appraising the utility of adjustable positioning, (2) demonstrating the
      resultant anatomical changes using magnetic resonance imaging, and (3)
      identifying associated complications. RESULTS: Four of 6 patients successfully
      underwent the procedure. Of these, 3 patients achieved orthotropia. Median
      preoperative horizontal deviation was 68 prism diopters of exotropia and median
      postoperative horizontal deviation was 0 prism diopters (P = .04). Two patients
      had preoperative vertical misalignment that resolved with surgery. All 4 patients
      underwent intraoperative adjustment of LR positioning. Imaging demonstrated nasal
      redirection of each half of the LR muscle around the posterior globe, avoiding
      contact with the optic nerve; the apex of the split sat posterior to the globe.
      One patient had transient choroidal effusion and undercorrection. Imaging
      revealed, in this case, the apex of the split in contact with the globe at an
      anterolateral location, suggesting an inadequate posterior extent of the split.
      In 2 patients, the surgical procedure was not completed because of an inability
      to nasally transpose a previously operated-on LR muscle. CONCLUSIONS AND
      RELEVANCE: Adjustable nasal transposition of the split LR muscle can achieve
      excellent oculomotor alignment in some cases of third nerve palsy. The adjustable
      modification allows optimization of horizontal and vertical alignment. Imaging
      confirms that the split LR muscle tethers the globe, rotating it toward primary
      position. Case selection is critical because severe LR contracture, extensive
      scarring from prior strabismus surgery, or inadequate splitting of the LR muscle
      may reduce the likelihood of success and increase the risk of sight-threatening
      complications. Considering this uncertainty, more experience is necessary before
      widespread adoption of this technique should be considered.

PMID- 24723156
TI  - Cotton-wool spots and retinal hemorrhages. Interferon-associated retinopathy.

PMID- 24723157
TI  - Disablement-based nomenclature for vision and function.

PMID- 24723158
TI  - Varicella-zoster virus detection in varicella-associated stromal keratitis.

PMID- 24723159
TI  - Rapid progression of uveitis and alopecia syphilitica in AIDS.

PMID- 24723160
TI  - To understand coral disease, look at coral cells.
AB  - Diseases threaten corals globally, but 40 years on their causes remain mostly
      unknown. We hypothesize that inconsistent application of a complete diagnostic
      approach to coral disease has contributed to this slow progress. We quantified
      methods used to investigate coral disease in 492 papers published between 1965
      and 2013. Field surveys were used in 65% of the papers, followed by biodetection
      (43%), laboratory trials (20%), microscopic pathology (21%), and field trials
      (9%). Of the microscopic pathology efforts, 57% involved standard histopathology
      at the light microscopic level (12% of the total investigations), with the
      remainder dedicated to electron or fluorescence microscopy. Most (74%)
      biodetection efforts focused on culture or molecular characterization of bacteria
      or fungi from corals. Molecular and immunological tools have been used to
      incriminate infectious agents (mainly bacteria) as the cause of coral diseases
      without relating the agent to specific changes in cell and tissue pathology. Of
      19 papers that declared an infectious agent as a cause of disease in corals, only
      one (5%) used microscopic pathology, and none fulfilled all of the criteria
      required to satisfy Koch's postulates as applied to animal diseases currently.
      Vertebrate diseases of skin and mucosal surfaces present challenges similar to
      corals when trying to identify a pathogen from a vast array of environmental
      microbes, and diagnostic approaches regularly used in these cases might provide a
      model for investigating coral diseases. We hope this review will encourage
      specialists of disease in domestic animals, wildlife, fish, shellfish, and humans
      to contribute to the emerging field of coral disease.

PMID- 24723161
TI  - Depleted uranium disturbs immune parameters in zebrafish, Danio rerio: an ex
      vivo/in vivo experiment.
AB  - In this study, we investigated the effects of depleted uranium (DU), the
      byproduct of nuclear enrichment of uranium, on several parameters related to
      defence system in the zebrafish, Danio rerio, using flow cytometry. Several
      immune cellular parameters were followed on kidney leucocytes: cell proportion,
      cell mortality, phagocytosis activity and associated oxidative burst and
      lysosomal membrane integrity (LMI). Effects of DU were tested ex vivo after 17 h
      of contact between DU and freshly isolated leucocytes from 0 to 500 ug DU/L.
      Moreover, adult zebrafish were exposed in vivo during 3 days at 20 and 250 ug
      DU/L. Oxidative burst results showed that DU increased reactive oxygen species
      (ROS) basal level and therefore reduced ROS stimulation index in both ex vivo and
      in vivo experiments. ROS PMA-stimulated level was also increased at 250 ug DU/L
      in vivo only. Furthermore, a decrease of LMI was detected after in vivo
      experiments. Cell mortality was also decreased at 20 ug DU/L in ex vivo
      experiment. However, phagocytosis activity was not modified in both ex vivo and
      in vivo experiments. A reduction of immune-related parameters was demonstrated in
      zebrafish exposed to DU. DU could therefore decrease the ability of fish to
      stimulate its own immune system which could, in turn, enhance the susceptibility
      of fish to infection. These results encourage the development and the use of
      innate immune analysis by flow cytometry in order to understand the effects of DU
      and more generally radionuclides on fish immune system and response to infectious
      diseases. 

PMID- 24723162
TI  - Retinal profile: a clinical indicator of severity in dengue fever in a suburban
      Indian environment.
AB  - PURPOSE: To study the retinal changes in subjects suffering from dengue fever and
      check if these changes can be taken as sufficient indicator of severity and
      progression of the disease. PATIENTS/METHODS: A detailed history was recorded of
      118 patients on whom ocular examination, including direct ophthalmoscopy,
      indirect ophthalmoscopy and coloured fundus photography, was performed. RESULTS:
      Forty-seven percent of patients were found to have posterior segment
      abnormalities. Retinal vein dilatation or tortuosity was the most common finding
      followed by changes in the optic disc (8.4% of patients) and background
      haemorrhage (6.7% of patients). With increasing severity of thrombocytopenia, the
      proportion of patients with retinal abnormalities increased. In patients with
      grade I thrombocytopenia, no fundal abnormality was found. In those with grade II
      thrombocytopenia, fundal abnormality was found in 13.63% patients, whereas in the
      grade III category it was 27.90%. CONCLUSIONS: Severity of thrombocytopenia had a
      significant association with retinal abnormalities. Occurrence of fundus changes
      increases with an increase in severity of thrombocytopenia. Fundus changes were
      found in all patients with grade IV thrombocytopenia.

PMID- 24723163
TI  - Glioma-like proliferation in a cortical hamartoma of tuberous sclerosis complex.

PMID- 24723164
TI  - Effects of feeding deoxynivalenol (DON)-contaminated wheat to laying hens and
      roosters of different genetic background on the reproductive performance and
      health of the newly hatched chicks.
AB  - A total of 216 23-week-old laying hens from two different genetic backgrounds
      (half of the birds were Lohmann brown [LB] and [LSL] hens, respectively) and 24
      adult roosters were assigned to a feeding trial to study the effect of increasing
      concentrations of deoxynivalenol (DON) in the diet (0, 5, 10 mg/kg) on the
      reproductive performance of hens and roosters, and the health of the newly
      hatched chicks. Hatchability was adversely affected by the presence of DON in LB
      hens' diet, while the hatchability of the LSL chicks was significantly higher
      than LB chicks. An interaction effect between DON in the hens' diet and the breed
      was noticed on fertility, as the fertility was decreased in the eggs of LB hens
      receiving 10 mg/kg DON in their diet and increased in the eggs of LSL hens fed 10
      mg/kg DON. Moreover, spleen relative weight was significantly decreased in the
      chicks hatched from eggs of hens fed contaminated diets, while gizzard relative
      weight was significantly decreased in LB chicks with 10 mg/kg DON in their diet
      compared with the control group. On the other hand, the chicks' haematology and
      organ histopathology were not affected by the dietary treatment. Additionally,
      the presence of DON in the roosters' diet had no effect on fertility (the
      percentage of fertile eggs of all laid eggs). Consequently, the current results
      indicate a negative impact of DON in LB hens' diet on fertility and hatchability,
      indicating that the breed of the hens seems to be an additional factor
      influencing the effect of DON on reproductive performance of the laying hens. 

PMID- 24723165
TI  - Factors influencing the exudation recurrence after cataract surgery in patients
      previously treated with anti-vascular endothelial growth factor for exudative age
      related macular degeneration.
AB  - PURPOSE: To investigate factors influencing exudation recurrence following
      cataract surgery in patients already treated with anti-vascular endothelial
      growth factor (VEGF) agents for exudative age-related macular degeneration (AMD).
      METHODS: A retrospective review of medical records was performed for patients who
      underwent cataract surgery and had been previously treated with anti-VEGF for
      exudative AMD. Visual acuity was examined before surgery and 1 and 6 months after
      surgery. The time between diagnosis and surgery, and the exudation-free period
      before surgery were examined and compared between patients who had exudation
      recurrence and those that did not. RESULTS: Thirty-nine eyes of 39 patients were
      included in analyses. The logarithm of the minimum angle of resolution visual
      acuity was 1.02 +/- 0.58 and had significantly improved 1 month (0.81 +/- 0.62, P
      < 0.001) and 6 months (0.85 +/- 0.64, P = 0.001) following surgery. Both the
      diagnosis-to-surgery period (P = 0.001) and the preoperative exudation-free
      period (P < 0.001) were significantly longer in patients without recurrence than
      in patients with recurrence. CONCLUSIONS: Cataract surgery was beneficial in
      patients previously treated with anti-VEGF for exudative AMD. Our data suggests
      that cataract surgery should be performed after a sufficiently long exudation
      free period to minimize exudation recurrence. But larger prospective studies are
      required to draw definitive clinical guidelines.

PMID- 24723167
TI  - World Primary Immunodeficiency Week: a call for newborn screening.

PMID- 24723169
TI  - NK/DC crosstalk in immunosurveillance: a broken relationship caused by WASP
      deficiency.
AB  - Wiskott-Aldrich syndrome (WAS) is a primary immunodeficiency, which is
      characterized by abnormal immune system functions caused by the lack of
      expression of WAS protein (WASp). A higher tumor susceptibility is observed in
      WAS patients; whether this is a direct consequence of impaired immunosurveillance
      due to WAS deficiency in immune cells is, however, an open question. In this
      issue of the European Journal of Immunology, Catucci et al. [Eur. J. Immunol.
      2014. 44: 1039-1045] shed light on the link between Was deficiency and
      immunosurveillance in a tumor-prone mouse model and report a role for the
      impaired crosstalk between natural killer (NK) cells and dendritic cells (DCs) in
      mediating this process. The potential mechanisms involved in WASp regulation of
      NK/DC-mediated immunosurveillance are the focus of this Commentary. 

PMID- 24723174
TI  - Risk of pancreatitis in patients treated with incretin-based therapies.
AB  - AIMS/HYPOTHESIS: Incretin-based therapies have been suggested to increase the
      risk of pancreatitis, but the results of the available studies are controversial.
      Because results from prospective trials are limited by low statistical power, and
      because retrospective studies are often subject to bias, a pooled analysis of
      phase III clinical trials and two endpoint trials was performed. METHODS: Event
      numbers for acute pancreatitis and patient-years of exposure (PYOs) were obtained
      from representatives of the pharmaceutical companies, or by literature research.
      Data were pooled for glucagon-like peptide 1 (GLP-1) receptor agonists and
      dipeptidyl-peptidase 4 (DPP-4) inhibitors in comparison with their respective
      controls and expressed as exposure-adjusted incidence rates. RESULTS: A total of
      38 cases of pancreatitis were reported in clinical trials with GLP-1 receptor
      agonists, comprising 17,775 PYOs. With the comparator treatment, nine events
      occurred in 5,863 PYOs. The pooled event rates were 2.1 and 1.5 per 1,000 PYOs,
      respectively, resulting in an OR of 1.39 (95% CI 0.67, 2.88). With DPP-4
      inhibitors, 57 events were reported in 45,132 PYOs compared with 46 events in
      38,883 PYOs with the comparator treatment. Pooled event rates were 1.3 and 1.2
      per 1,000 PYOs, respectively, resulting in an OR of 1.07 (CI 0.72, 1.58).
      CONCLUSIONS/INTERPRETATION: This analysis suggests a trend towards a slightly
      elevated risk of pancreatitis with GLP-1 receptor agonists. With DPP-4
      inhibitors, no consistent trend was found. However, the incidence numbers of
      cases of pancreatitis were still very small, and the statistical power was
      limited. Future endpoint trials may help to provide a better estimate of the true
      risk of pancreatitis with incretin-based therapies.

PMID- 24723176
TI  - [Cognitive performance and quality of life in multiple sclerosis in Gipuzkoa].
AB  - INTRODUCTION: Cognitive impairment and the presence of depressive symptoms, which
      are commonly found in patients with multiple sclerosis, affect the patients'
      quality of life. AIM. To describe the quality of life, cognitive compromise and
      levels of depression, in relation to other clinical variables, in patients with
      multiple sclerosis in the province of Gipuzkoa. PATIENTS AND METHODS: A total of
      114 patients were submitted to neuropsychological evaluation. The MSQoL-54 and
      Beck's Depression Inventory were applied to evaluate the quality of life and
      levels of depression. Three main analyses were performed: a comparison of
      cognitive performance among subtypes, an analysis of the correlation among
      clinical, neuro-psychological and quality of life variables, and an analysis of
      the effects of gender on cognitive performance. RESULTS: A neuropsychological
      pattern is found in multiple sclerosis that is characterised by a slowing of the
      processing of information and attentional difficulties. Quality of life is
      related with depressive syndromes and with overall cognitive performance but not
      with clinical factors such as the rate of attacks or the length of time the
      disease lasts. The data confirm the existence of poorer cognitive performance in
      males, above all in terms of verbal auditory memory. CONCLUSIONS: Gender is
      presented as a factor that modulates the impact of the disease on cognitive
      performance, which reinforces the interest in conducting studies that clarify the
      origin of such differences. Furthermore, the quality of life displays a greater
      relationship with the degree of adaptation to the disease than with its symptoms.

PMID- 24723177
TI  - [Study of the pre- and post-treatment functionality of unilateral acquired brain
      injuries].
AB  - INTRODUCTION: Most of the people who have survived a lateralized brain injury
      have sequelae components affecting sensorimotor, cognitive or behavioral. These
      deficits affect the proper execution of daily living activities. The aim of this
      study is to analyze and compare the occupational profile of people with
      unilateral acquired brain injury, both people with traumatic brain injury (TBI)
      and cerebrovascular accidents (CVA), with functional independence, ability,
      participation and the quality of performance of everyday activities, before and
      after a multidisciplinary treatment. PATIENTS AND METHODS: Cohort quasi
      experimental design with pre-cutting measures after treatment with a sample of 58
      people, 28 TBI and 30 CVA, both lateralized. The measures used were the FIM+FAM,
      ICF, and AMPS. RESULTS: Considering the groups analyzed (lateralized full sample,
      sample diagnosis) analysis results indicate the existence of significant
      differences and a moderate effect size in the two cross-sectional estimates,
      providing greater levels of independence to injuries occurring in the right
      hemisphere (p < 0.001). However, when it is divided the sample by diagnosis
      appears no significant differences, except in motor skills, where higher scores
      for TBI are showed (p < 0,05). CONCLUSIONS: We suggest that this justifies the
      differences is not the mode of injury (TBI or CVA), but the hemispheric location.
      Therefore, it is suggested that people with acquired brain injury in the left
      hemisphere require more intensive intervention.

PMID- 24723178
TI  - [Challenges in the pharmacotherapeutic management of the hospitalised patient
      with Parkinson's disease].
AB  - Patients with Parkinson's disease (PD) are admitted to hospital more frequently
      and for a longer time than other patients from the same age group. The reason
      they are hospitalised is often different from their underlying baseline disease
      and they are usually attended in services with little knowledge of the disease.
      Both the errors made when administering levodopa and the inappropriate use of
      pharmacological agents with a central antidopaminergic action are relatively
      common during their stay in hospital. This study reports on an analysis of the
      literature available on the challenges and complications that patients with PD
      have to deal with when they are admitted to hospital, especially those that have
      to do with pharmacotherapy. Likewise, the authors also propose a series of
      strategies that lead to better care of the patients during the time they are in
      hospital, including aspects such as controlling the supplies of antiparkinsonian
      medication and establishing protocols for the therapeutic exchange of
      antiparkinsonian agents, as well as protocols for a suitable management of
      comorbidities in this kind of patients. Other strategies involve encouraging self
      management of the antiparkinsonian treatment by the hospitalised patients,
      conducting follow-up studies to monitor inappropriate prescriptions or creating
      the figure of 'specialist in PD'. To do so, it will be necessary to raise the
      awareness of the healthcare staff at the hospital, as well as that of both
      patients and their relatives, about the problems derived from an inappropriate
      management of pharmacotherapy in PD. 

PMID- 24723179
TI  - [Clinical approach to the first epileptic crisis in adults].
AB  - Seizures are one of the main reasons for visits to emergency and neurology.
      Represent a traumatic event with potential medical and social consequences. A
      first epileptic seizure, can be the initial manifestation of malignancy, systemic
      disorder or infection, but can also be the first manifestation of epilepsy. The
      misdiagnosis of symptomatic seizures and unprovoked seizure, significantly
      affects prognosis and patient outcomes. The aim of this review is to examine the
      general concepts that enable successful diagnostic and therapeutic approach to
      the patient presenting with a first epileptic seizure. 

PMID- 24723181
TI  - [Disease due to lysosomal deposits with differential peculiarities: type II GM1
      gangliosidosis].

PMID- 24723183
TI  - The modified model of radiation risk at radon exposure.
AB  - The combined modified model of risk assessment from an indoor radon exposure is
      proposed. Multiplicative dependence on fatal lung cancer is used. The model has
      been developed on the basis of the modern health risk theory and the results of
      epidemiological studies with the special attention to the results of the European
      combined study and the WISMUT miners cohort study. The model is presented as an
      age-specific relative risk coefficient for a single (short-term) exposure. The
      risk coefficient for an extended exposure can be obtained from this risk
      coefficient in the accordance with the risk theory. The smoothed dependences of
      the risk coefficients on time since exposure and attained age and radon progeny
      concentration are suggested. 

PMID- 24723184
TI  - Stochastic dosimetry model for radon progeny in the rat lung.
AB  - The stochastic dosimetry model presented here considers the distinctly
      asymmetric, stochastic branching pattern reported in morphometric measurements.
      This monopodial structure suggests that an airway diameter is a more appropriate
      morphometric parameter to classify bronchial dose distributions for inhaled radon
      progeny than the commonly assigned airway generation numbers. Bronchial doses
      were calculated for the typical exposure conditions reported for the Pacific
      Northwest National Laboratory rat inhalation studies, yielding an average
      bronchial dose of 7.75 mGy WLM(-1). If plotted as functions of airway
      generations, the resulting dose distributions are highest in the central
      bronchial airways, while significantly decreasing towards peripheral generations.
      However, if plotted as functions of airway diameters, doses are much more
      uniformly distributed among bronchial airways. The comparison between rat and
      human lungs indicates that dose conversion coefficients for the rat lung are
      higher than the corresponding values for the human lung by a factor of 1.34 for
      the experimental PNNL exposure conditions, and of 1.25 for typical human indoor
      conditions. 

PMID- 24723185
TI  - Calibration of CR-39-based thoron progeny device.
AB  - Radon isotopes and their progenies have proven significant role in respiratory
      tumour formation. In most cases, the radiological effect of one of the radon
      isotopes (thoron) and its progenies has been neglected together with its
      measurement technique; however, latest surveys proved that thoron's existence is
      expectable in flats and in workplace in Europe. Detectors based on different
      track detector measurement technologies have recently spread for measuring thoron
      progenies; however, the calibration is not yet completely elaborated. This study
      deals with the calibration of the track detector measurement method suitable for
      measuring thoron progenies using different devices with measurement techniques
      capable of measuring several progenies (Pylon AB5 and WLx, Sarad EQF 3220). The
      calibration factor values related to the thoron progeny monitors, the measurement
      uncertainty, reproducibility and other parameters were found using the
      calibration chamber. In the future, the effects of the different parameters
      (aerosol distribution, etc.) will be determined. 

PMID- 24723186
TI  - Radon dose assessment in underground mines in Brazil.
AB  - Underground miners are internally exposed to radon, thoron and their short-lived
      decay products during the mineral processing. There is also an external exposure
      due to the gamma emitters present in the rock and dust of the mine. However, the
      short-lived radon decay products are recognised as the main radiation health
      risk. When inhaled, they are deposited in the respiratory system and may cause
      lung cancer. To address this concern, concentration measurements of radon and its
      progeny were performed, the equilibrium factor was determined and the effective
      dose received was estimated in six Brazilian underground mines. The radon
      concentration was measured by using E-PERM, AlphaGUARD and CR-39 detectors. The
      radon progeny was determined by using DOSEman. The annual effective dose for the
      miners was estimated according to United Nations Scientific Committee on the
      Effects of Atomic Radiation methodologies. The mean value of the equilibrium
      factor was 0.4. The workers' estimated effective dose ranged from 1 to 21 mSv a(
      1) (mean 9 mSv a(-1)). 

PMID- 24723187
TI  - Radon contribution to the total effective dose of uranium miners.
AB  - Exposure to radon and its decay products is one of the three parts that create
      the total effective dose of uranium miners. Photons from gamma radiation and
      exposition to long-lived alpha emitters which are members of uranium family are
      the other two parts. The monthly total effective dose of uranium miners in mine
      Rozna I (Czech republic) is determined by the personal dosemeter ALGADE, which
      ensures the continual individual monitoring of all three parts. The exposed
      dosemeters are evaluated in the National Institute for Nuclear, Chemical and
      Biological Protection in Kamenna near Pribram. This paper describes the
      individual parts of miners' total effective dose considering the different types
      of work activities and workplaces. The main input data are the evaluation results
      of the uranium miners' personal dosemeters ALGADE in mine Rozna I in the time
      period from 2000 till 2012. 

PMID- 24723188
TI  - Indoor radon problem in energy efficient multi-storey buildings.
AB  - Modern energy-efficient architectural solutions and building construction
      technologies such as monolithic concrete structures in combination with effective
      insulation reduce air permeability of building envelope. As a result, air
      exchange rate is significantly reduced and conditions for increased radon
      accumulation in indoor air are created. Based on radon survey in Ekaterinburg,
      Russia, remarkable increase in indoor radon concentration level in energy
      efficient multi-storey buildings was found in comparison with similar buildings
      constructed before the-energy-saving era. To investigate the problem of indoor
      radon in energy-efficient multi-storey buildings, the measurements of radon
      concentration have been performed in seven modern buildings using radon
      monitoring method. Values of air exchange rate and other parameters of indoor
      climate in energy-efficient buildings have been estimated. 

PMID- 24723189
TI  - Fetus dose estimation in thyroid cancer post-surgical radioiodine therapy.
AB  - Unrecognised pregnancy during radioisotope therapy of thyroid cancer results in
      hardly definable embryo/fetus exposures, particularly when the thyroid gland is
      already removed. Sources of such difficulty include uncertainty in data like
      pregnancy commencing time, amount and distribution of metastasized thyroid cells
      in body, effect of the thyroidectomy on the fetus dose coefficient etc. Despite
      all these uncertainties, estimation of the order of the fetus dose in most cases
      is enough for medical and legal decision-making purposes. A model for adapting
      the dose coefficients recommended by the well-known methods to the problem of
      fetus dose assessment in athyrotic patients is proposed. The model defines a
      correction factor for the problem and ensures that the fetus dose in athyrotic
      pregnant patients is less than the normal patients. A case of pregnant patient
      undergone post-surgical therapy by I-131 is then studied for quantitative
      comparison of the methods. The results draw a range for the fetus dose in
      athyrotic patients using the derived factor. This reduces the concerns on under-
      or over-estimation of the embryo/fetus dose and is helpful for personal and/or
      legal decision-making on abortion. 

PMID- 24723190
TI  - A high-sensitivity method for the measurement of 222Rn based on liquid
      scintillation counting of polycarbonate powder.
AB  - This work describes a technique for the measurement of 222Rn by absorption in
      polycarbonate (PC) powder and liquid scintillation counting (LSC). The work is an
      improvement of the recently proposed method for 222Rn measurements by LSC of
      exposed PC grains. It is demonstrated that the use of PC powder as a 222Rn
      sampler improves 13.6 times the sampling efficiency and leads to 6.5 times
      smaller minimmal detectable activity concentrations (MDAC) compared with the PC
      grains used so far. For a 40-h exposure of 7.4-g PC powder to 222Rn in air, the
      MDAC with a RackBeta 1219 LS counter is 62 Bq m(-3) (assuming a 8-h sample
      counting time and 24-h background time). For the same conditions the estimated
      222Rn MDAC with a Quantulus 1220 LS counter is 20 Bq m(-3). The proposed
      technique is suitable for radon in air and radon in soil-gas measurements.

PMID- 24723191
TI  - Indoor/outdoor radon decay products associated aerosol particle-size
      distributions and their relation to total number concentrations.
AB  - The activity size distributions of indoor and outdoor radioactive aerosol
      associated with short-lived radon decay products were observed at Nagoya, Japan,
      for some periods from 2010 to 2012, following the indoor observation by Mostafa
      et al. [Mostafa, A. M. A., Tamaki, K., Moriizumi, J., Yamazawa, H. and Iida, T.
      The weather dependence of particle size distribution of indoor radioactive
      aerosol associated with radon decay products. Radiat. Prot. Dosim. 146: (1-3), 19
      22 (2011)]. The tendency of smaller indoor activity median aerodynamic diameter
      (AMAD) after rainfalls showed in the previous study was not consistently
      obtained, while the consistent tendency of less indoor radioactive particles with
      diameters in the accumulation mode was observed again after rainfalls. The indoor
      aerosols showed activity size distributions similar to the outdoor ones. Non
      radioactive aerosol particle concentrations measured with a laser particle
      counter suggested a somewhat liner relationship with AMAD. 

PMID- 24723192
TI  - A simple approach to measure the radon equilibrium factor F from air filter gross
      beta counting.
AB  - The internal alpha dose assessment (ICRP 65, 1994) depends on the value of the
      equilibrium factor F. This parameter is generally not measured and a mean
      conventional value ranging between 0.4 and 0.6 is assumed, possibly leading to a
      significant bias in the dose assessments. In this paper, a method for the
      measurement of F is reported, based on the total aerosol sampling on filters and
      immediate gross beta counting of 214Pb and 214Bi activities. Measurements are
      interpreted according to a Raabe-Wrenn and Jacobi simplified room model, leading
      to an estimate of the individual airborne activities of short-lived radon
      daughters, the removal parameter and the equilibrium factor. The method was
      laboratory tested and validated and it is being qualified by field surveys in
      different indoor environmental conditions.

PMID- 24723193
TI  - Application of a Monte Carlo lung dosimetry code to the inhalation of thoron
      progeny.
AB  - To determine radiation doses incurred by inhaled thoron progeny, the Monte Carlo
      radon progeny lung dosimetry code IDEAL-DOSE was adapted to the inhalation of
      thoron progenies, comprising the alpha-emitting nuclides 216Po, 212Bi and 212Po.
      Dose calculations for defined exposure conditions yielded a dose conversion
      coefficient (DCC) of 4.6 mSv WLM(-1) or 94.2 nSv (Bq h m(-3))(-1) when compared
      with a DCC of 3.8 mSv WLM(-1) if based on the International Commission on
      Radiological Protection Human Respiratory Tract Model. Bronchial doses were
      computed for different thoron progenies exposure conditions measured in a
      Bavarian half-timbered house and in a thoron experimental house at the Helmholtz
      Zentrum Munchen. DCCs ranged from 4.9 to 12.9 mSv WLM(-1), depending on particle
      size, unattached fraction and fractional activity concentrations. For exposure
      specific indoor aerosol parameters, the thoron progeny DCC is smaller than the
      radon progeny DCC by about a factor of 2.

PMID- 24723194
TI  - 222Rn+220Rn monitoring by alpha spectrometry.
AB  - Controlled 222Rn+220Rn mixed atmospheres have been realised introducing
      calibrated sources in a stainless steel chamber. An electrostatic alpha monitor
      internal to the chamber has been used for an accurate discrimination of alpha
      peaks due to the products of the two isotopes. In the chamber, different specific
      activities are achieved in order to test the response of the internal reference
      instrument and to evaluate the possible interferences due to contemporary
      presence of both radon isotopes. Results show that: (i) the atmospheres are very
      stable, (ii) the monitor is adequate for their control because the various alpha
      lines are well evaluated and (iii) using Tyvek(r) filter, the efficiency of
      monitor is stable and constant vs. activity.

PMID- 24723195
TI  - Typical exposure of children to EMF: exposimetry and dosimetry.
AB  - A survey study with portable exposimeters, worn by 21 children under the age of
      17, and detailed measurements in an apartment above a transformer substation were
      carried out to determine the typical individual exposure of children to extremely
      low- and radio-frequency (RF) electromagnetic field. In total, portable
      exposimeters were worn for >2400 h. Based on the typical individual exposure the
      in situ electric field and specific absorption rate (SAR) values were calculated
      for an 11-y-old female human model. The average exposure was determined to be low
      compared with ICNIRP reference levels: 0.29 MUT for an extremely low-frequency
      (ELF) magnetic field and 0.09 V m(-1) for GSM base stations, 0.11 V m(-1) for
      DECT and 0.10 V m(-1) for WiFi; other contributions could be neglected. However,
      some of the volunteers were more exposed: the highest realistic exposure, to
      which children could be exposed for a prolonged period of time, was 1.35 MUT for
      ELF magnetic field and 0.38 V m(-1) for DECT, 0.13 V m(-1) for WiFi and 0.26 V m(
      1) for GSM base stations. Numerical calculations of the in situ electric field
      and SAR values for the typical and the worst-case situation show that, compared
      with ICNIRP basic restrictions, the average exposure is low. In the typical
      exposure scenario, the extremely low frequency exposure is <0.03 % and the RF
      exposure <0.001 % of the corresponding basic restriction. In the worst-case
      situation, the extremely low frequency exposure is <0.11 % and the RF exposure
      <0.007 % of the corresponding basic restrictions. Analysis of the exposures and
      the individual's perception of being exposed/unexposed to an ELF magnetic field
      showed that it is impossible to estimate the individual exposure to an ELF
      magnetic field based only on the information provided by the individuals, as they
      do not have enough knowledge and information to properly identify the sources in
      their vicinity. 

PMID- 24723196
TI  - Use of health economics in the development of a national radon control strategy
      in Ireland.
AB  - A health economics evaluation of different radon intervention strategies was
      undertaken including the incorporation of prevention into new buildings, the
      incorporation of potential remedial measures into new buildings and remediation
      of existing buildings. The analysis shows that (1) the incorporation of
      prevention into new houses at the time of construction is generally more cost
      effective than remediation of existing houses and (2) that the cost effectiveness
      of programmes aimed at encouraging householders to test and remediate their
      houses may be poor if they are not undertaken within the context of coherent
      radon reduction strategy. The results of this evaluation were used to identify
      the most cost-effective radon interventions in an Irish context in support of the
      development of a National Radon Control Strategy. 

PMID- 24723197
TI  - Preliminary results of indoor radon survey in V4 countries.
AB  - The measurements of radon activity concentration carried out in residential
      houses of V4 countries (Hungary, Poland and Slovakia) show that radon levels in
      these countries considerably exceed the world average. Therefore, the new radon
      data and statistical analysis are required from these four countries. Each
      partner chose a region in their own country, where radon concentration in
      residential buildings was expected to be higher. The results of the survey
      carried out in the period from March 2012 to May 2012 show that radon
      concentrations are <200 Bq m(-3) in ~87% of cases. However, dwellings with radon
      concentration ~800 Bq m(-3) were found in Poland and Slovakia. It was also found
      that the distribution of radon frequency follows that of houses according to the
      year of their construction.

PMID- 24723198
TI  - Endoplasmic reticulum targeted chemotherapeutics: the remarkable photo
      cytotoxicity of an oxovanadium(IV) vitamin-B6 complex in visible light.
AB  - An oxovanadium(IV) vitamin-B6 Schiff base complex, viz. [VO(HL)(acdppz)]Cl,
      having (acridinyl)dipyridophenazine (acdppz) shows specific localization to
      endoplasmic reticulum (ER) and remarkable apoptotic photocytotoxicity in visible
      light (400-700 nm) in HeLa and MCF-7 cancer cells (IC50 < 0.6 MUM) while being
      non-toxic in the dark and to MCF-10A normal cells (IC50 > 40 MUM).

PMID- 24723199
TI  - "Click and go": simple and fast folic acid conjugation.
AB  - Folic acid targeting by functionalization of the terminal gamma-carboxylic acid
      is one of the most important strategies to selectively deliver chemotherapeutics
      and dyes to cancer cells which overexpress folate receptors. However, conjugation
      of folic acid is limited by its unique solubility and by selectivity issues
      imposing the need for expensive preparative reverse-phase chromatographic
      purification to isolate gamma-folate conjugates. Herein is provided a novel
      synthetic tool for the synthesis of new folic acid conjugates with excellent
      gamma-purity based on strain-promoted alkyne-azide cycloadditions with a gamma
      folate-cyclooctyne conjugate 3. To demonstrate the potential of this methodology
      several new folate conjugates were synthesized with high gamma-purity and without
      using any type of chromatographic purification by reacting conjugate 3 with
      several fluorescent probes, polymers and siliceous materials bearing azide. In
      addition, the cycloaddition reaction between conjugate 3 and an azido-derived
      fluorescent dye was successfully performed in cellular media leading to an
      increase of fluorescence in the cells which overexpress folate receptors (NCI
      H460). 

PMID- 24723201
TI  - A DFT study of ruthenium pincer carboxylate complexes as potential catalysts for
      the direct carboxylation of arenes with CO2- meridional versus facial
      coordination.
AB  - A recent DFT study of the ruthenium pincer benzoate complex [Ru(PNP)(PhCOO)2] I
      (PNP = 2,6-bis(diphenylphosphanyl)lutidine) in its meridional form has revealed
      mer-I to be a promising catalyst lead structure for the direct insertion of CO2
      into the C-H bonds of arenes, such as benzene. After the successful synthesis of
      I, its solid state structure interestingly and unexpectedly showed the pincer
      ligand to adopt the facial rather than the meridional coordination mode.
      Recalculation of the catalytic cycle with fac-I including all relevant local
      minima and transition states revealed (a) fac-I to be significantly more stable
      (6.1 kcal mol(-1)) than mer-I, (b) that the energetic span (ES; i.e. the
      effective activation barrier) for the cycle with fac-I amounts to 38.8 kcal mol(
      1), while the cycle with mer-I has an ES of 25.5 kcal mol(-1) only. These results
      are a hint that fac-I is catalytically inactive. Experimental testing of fac-I
      showed indeed no product formation, which is in full accordance with the
      computations. To reduce the spatial flexibility of the pincer ligand, its CH2
      groups were replaced by O atoms. The resulting complex [Ru(PONOP)(PhCOO)2] II
      (PONOP = 2,6-bis(diphenylphosphinito)pyridine) was used for the calculation of
      the catalytic cycle in benzene as the solvent. Gratifyingly, the starting complex
      mer-II is more stable than fac-II by 1.9 kcal mol(-1) in benzene as the solvent.
      Consequently, mer-II should be available experimentally. As with fac-I, also fac
      II generates a catalytic cycle with a high ES (37.1 kcal mol(-1)), while mer-II
      generates a cycle with a significantly lower ES (27.2 kcal mol(-1)) indicating
      mer-II to be a potentially active catalyst. A possible explanation of the much
      lower ES in the case of the meridionally coordinated species is found in the
      stronger interaction of the substrate with the metal center in the arene-sigma
      bond complex. As a result the issue that is created by the mer/fac isomerism can
      be resolved by creating spatially less flexible structures. 

PMID- 24723200
TI  - Pediatric ulcerative colitis: a practical guide to management.
AB  - Ulcerative colitis (UC) is a chronic inflammatory disorder of the
      gastrointestinal tract of unknown etiology that frequently presents in the
      pediatric population. The evaluation of pediatric UC involves excluding
      infection, and a colonoscopy that documents the clinical and histologic features
      of chronic colitis. Initial management of mild UC is typically with mesalamine
      therapy for induction and maintenance. Moderate UC is often initially treated
      with oral prednisone. Depending on disease severity and response to prednisone,
      maintenance options include mesalamine, mercaptopurine, azathioprine, infliximab,
      or adalimumab. Severe UC is typically treated with intravenous corticosteroids.
      Corticosteroid nonresponders should either undergo a colectomy or be treated with
      second-line medical rescue therapy (infliximab or calcineurin inhibitors). The
      severe UC patients who respond to medical rescue therapy can be maintained on
      infliximab or thiopurine, but 1-year remission rates for such patients are under
      50 %. These medications are discussed in detail along with the initial work-up
      and a treatment algorithm.

PMID- 24723202
TI  - Evaluation of DNA binding with some selected hydrazide and semicarbazide
      derivatives.
AB  - A group of hydrazide and semicarbazide derivatives containing isopropylidene,
      benzylidene, cyclohexylidene, and phospholidene groups was synthesized and
      characterized by spectroscopic techniques. These compounds were tested for DNA
      interaction studies monitored by UV-Vis and IR data as well as molecular docking.
      Investigations on interactions of these compounds with DNA revealed an
      intercalative mode of binding between them. It is interesting to note that
      semicarbazide derivatives with aliphatic substituents showed better DNA binding
      than the aromatic substituents.

PMID- 24723203
TI  - Regulation of vincamine biosynthesis and associated growth promoting effects
      through abiotic elicitation, cyclooxygenase inhibition, and precursor feeding of
      bioreactor grown Vinca minor hairy roots.
AB  - Hydroxylase/acetyltransferase elicitors and cyclooxygenase inhibitor along with
      various precursors from primary shikimate and secoiridoid pools have been
      fortified to vincamine less hairy root clone of Vinca minor to determine the
      regulatory factors associated with vincamine biosynthesis. Growth kinetic studies
      revealed that acetyltransferase elicitor acetic anhydride and terpenoid precursor
      loganin significantly reduce the growth either supplemented alone or in
      combination (GI = 140.6 +/- 18.5 to 246.7 +/- 24.3), while shikimate and
      tryptophan trigger biomass accumulation (GI = 440.2 +/- 31.5 to 540.5 +/- 40.3).
      Loganin also downregulates total alkaloid biosynthesis. Maximum flux towards
      vincamine production (0.017 +/- 0.001 % dry wt.) was obtained when 20-day-old
      hairy roots were fortified with secologanin (10 mg/l) along with tryptophan (100
      mg/l), naproxen (8.4 mg/l), hydrogen peroxide (20 MUg/l), and acetic anhydride
      (32.4 mg/l). This was supported by RT PCR (qPCR) analysis where 2- and 3-fold
      increase in tryptophan decarboxylase (TDC; RQ = 2.0 +/- 0.09) and strictosidine
      synthase (STR; RQ = 3.3 +/- 0.36) activity, respectively, was recorded. The
      analysis of variance (ANOVA) for growth kinetics, total alkaloid content, and
      gene expression studies favored highly significant data (P < 0.05-0.01). Above
      treated hairy roots were also up-scaled in a 5-l stirred-tank bioreactor where a
      40-day cycle yielded 8-fold increase in fresh root mass. 

PMID- 24723205
TI  - Identification of two putative acyltransferase genes potentially implicated in
      dithiolopyrrolone biosyntheses in Saccharothrix algeriensis NRRL B-24137.
AB  - The dithiolopyrrolone class of antibiotics has been known to display
      bacteriostatic activity against both Gram-positive and Gram-negative bacteria and
      exert other biological activities. Acyltransferase activities are proposed to be
      responsible for the structural diversity of dithiolopyrrolones produced by
      Saccharothrix algeriensis NRRL B-24137. Moreover, two activities, pyrrothine N
      acetyltransferase and pyrrothine N-benzoyltransferase, are reported to catalyze
      the formation, respectively, to thiolutin and benzoyl-pyrrothine (BEP) in this
      bacterium. In this study, two genes encoding two putative acyltransferases were
      identified in S. algeriensis. The first one, actA, was identified by
      bioinformatic analysis and by analogy to an acetyltransferase, hlmA, identified
      in holomycin biosynthetic gene cluster in Streptomyces clavuligerus. The second
      was identified by purification of both enzymes from the bacterial biomass which
      provided a semipurified extract. The microsequencing of tryptic peptides from the
      final protein preparation yielded sequences of eight different fragments, two of
      them encoded by one gene, actB, in S. algeriensis genome bank. The alignment of
      actB against the GenBank database revealed significant homology to
      acyltransferase family. Differential expression of these genes, actA and actB,
      was then investigated in three different media: (i) semisynthetic medium (SSM),
      which promotes the production of thiolutin; (ii) SSM supplemented by 1.25 mM
      benzoic acid (SSM + BA), which promotes the production of both thiolutin and BEP;
      and (iii) tryptic soy broth (TSB) in which no dithiolopyrrolone derivatives were
      detected. 

PMID- 24723204
TI  - Electrochemical sensing of cortisol: a recent update.
AB  - Psychological stress caused by everyday lifestyle contributes to health
      disparities experienced by individuals. It affects many biomarkers, but cortisol 
      "a steroid hormone" - is known as a potential biomarker for psychological stress
      detection. Abnormal levels of cortisol are indicative of conditions such as
      Cushing's syndrome Addison's disease, adrenal insufficiencies and more recently
      post-traumatic stress disorder (PTSD). Chromatographic techniques, which are
      traditionally used to detect cortisol, are a complex system requiring multistep
      extraction/purification. This limits its application for point-of-care (POC)
      detection of cortisol. However, electrochemical immunosensing of cortisol is a
      recent advancement towards POC application. This review highlights simple, low
      cost, and label-free electrochemical immunosensing platforms which have been
      developed recently for sensitive and selective detection of cortisol in bio
      fluids. Electrochemical detection is utilized for the detection of cortisol using
      Anti-Cortisol antibodies (Anti-Cab) covalently immobilized on nanostructures,
      such as self-assembled monolayer (SAM) and polymer composite, for POC integration
      of sensors. The observed information can be used as a prototype to understand
      behavioral changes in humans such as farmers and firefighters. Keeping the future
      directions and challenges in mind, the focus of the BioMEMS and Microsystems
      Research Group at Florida International University is on development of POC
      devices for immunosensing, integration of these devices with microfluidics, cross
      validation with existing technologies, and analysis of real sample. 

PMID- 24723206
TI  - Plasma anti-alpha-galactoside antibody binds to serine- and threonine-rich
      peptide sequence of apo(a) subunit in Lp(a).
AB  - Lipoprotein(a) immune complexes [Lp(a) IC] of varying particle density obtained
      by ultracentrifugation of plasma from normal healthy donors were markedly
      dominated by IgG. Lp(a) and immunoglobulins were liberated from plasma Lp(a) IC
      by treatment with melibiose, a sugar specific for circulating anti-alpha
      galactoside antibody (anti-Gal). Upon incubation with plasma lipoprotein fraction
      anti-Gal but not the alpha-glucoside-specific antibody from human plasma formed
      de novo IC with Lp(a). Binding of Lp(a) sugar-reversibly enhanced the
      fluorescence of FITC-labeled anti-Gal as did binding of alpha-galactoside
      containing glycoproteins. This effect apparently due to conformational shift in
      the Fc region of the antibody was also produced by apo(a) subunit separated from
      Lp(a) and de-O-glycosylated apo(a) but not by any other plasma lipoproteins or by
      Lp(a) pre-incubated with the O-glycan-specific lectin jacalin. O-Glycans and
      their terminal sialic acid moieties in apo(a) of circulating Lp(a)-anti-Gal IC,
      in contrast to those in pure Lp(a), were inaccessible to jacalin and anion
      exchange resin, respectively. Unlike other plasma lipoproteins, Lp(a) inhibited
      Griffonia simplicifolia isolectin B4 which also accommodates serine- and
      threonine-rich peptide sequence (STPS) as surrogate ligand to alpha-galactosides
      at its binding site. Results suggest that anti-Gal recognizes STPS in the O
      glycan-rich regions of apo(a) subunit in Lp(a) which contains no alpha-linked
      galactose.

PMID- 24723208
TI  - Update in endocrinology: evidence published in 2013.

PMID- 24723207
TI  - Porous titanium oxynitride sheets as electrochemical electrodes for energy
      storage.
AB  - A flexible, porous TiOxNy sheet consisting of numerous conductive fibers was
      synthesized by nitridation of titanate and further used as an electrochemical
      electrode. The high surface area and mixed-oxidation state of titanium make
      TiOxNy sheets to be promising candidates for a good supercapacitor. 

PMID- 24723209
TI  - Human papillomavirus infection is rare in nonmalignant tonsil tissue in the UK:
      implications for tonsil cancer precursor lesions.
AB  - The incidence of human papillomavirus (HPV)-associated tonsil cancer is
      increasing but the prevalence of HPV, and of premalignant precursors, in tonsil
      tissue is unknown. We aimed to assess prevalence of HPV infection in nonmalignant
      tonsillar crypt epithelia and to histopathologically characterise positive
      samples. Formalin-fixed paraffin-embedded (FFPE) tonsil tissue specimens were
      obtained from an age- and sex-stratified random sample of patients aged 0-69
      years whose paired tonsils were archived following elective tonsillectomy at
      hospitals throughout England and Southern Scotland from 2004 to 2008. Homogenised
      fresh-frozen tonsil tissue was also obtained from archive for two random subsets
      of males aged 25-34 and over 44. HPV status was assessed in all samples for 20
      mucosal HPV types by GP5+/6+ polymerase chain reaction (PCR) enzyme immunoassay
      and by HPV16 type-specific PCR targeting the E6 gene. In the homogenised
      material, HPV status was also assessed for 44 HPV types by SPF10-PCR enzyme
      immunoassay. Of 4,095 randomly sampled FFPE specimens, amplifiable DNA was
      extracted from 3,377 (82.5%) and from 511 of 524 (97.5%) homogenised tonsils. HPV
      DNA was identified in 0 of 3,377 (0%, 95% CI 0-0.089%) fixed samples and 0 of 511
      (0%, 95% CI 0-0.58%) homogenised samples. This suggests HPV infection may be rare
      in tonsil reticulated crypt epithelia. Furthermore, we found no evidence of HPV
      associated premalignant neoplasia. These data suggest that if HPV-associated
      premalignant lesions do occur, they are likely to be rare and may have a high
      risk of progression to carcinoma. 

PMID- 24723210
TI  - Device closure of secundum atrial septal defects in infants weighing less than 8
      kg.
AB  - This study aimed to assess the technical aspects of atrial septal defect (ASD)
      closure using the Amplatzer septal occluder (ASO) and the Gore Helex septal
      occluder (GHSO) for infants weighing less than 8 kg and to determine the safety,
      effectiveness, and near-to-intermediate-term outcome of the closure. The Mid
      Atlantic Group of Interventional Cardiology Registry of percutaneous,
      transcatheter ASD closure procedures was reviewed for this analysis. Patients
      from 10 hospitals in the United States were included. The cohort for this report
      consisted of 68 patients weighing less than 8 kg (range, 2.3-7.8 kg; mean, 5.5 +/
      1.6 kg) and ranging in age from 1 to 24 months (mean, 8.6 +/- 4.7 months). The
      indications for ASD closure were failure to thrive, significant right heart
      enlargement, shunts otherwise thought to be hemodynamically significant, and poor
      overall clinical status. Devices were successfully implanted in 66 of the 68
      infants (97.1 % procedural success rate). Five minor procedure-related
      complications occurred. At follow-up assessment, clinical status had improved
      significantly as measured by improved weight gain and decreased ventilator or
      oxygen dependence. All residual shunts spontaneously closed during the follow-up
      period. Six late deaths occurred, none of which were clearly device related. The
      ASO and GHSO can be safely and effectively implanted for ASD closure in infants
      weighing less than 8 kg. These procedures usually are successful and seldom
      complicated, resulting in significant clinical improvement.

PMID- 24723212
TI  - Using modified approaches on marginal regression analysis of longitudinal data
      with time-dependent covariates.
AB  - Quadratic inference functions (QIFs) and estimating equations using the conjugate
      gradient method (CGM) for fitting marginal models to longitudinal data show
      appealing features in improving the efficiency without making assumptions on the
      correlation structure. However, our simulation study shows that both methods
      produce biased and inefficient estimates of regression parameters when time
      dependent covariates are present. In this paper, we extend both the QIF and CGM
      methods for fitting marginal models to longitudinal data with time-dependent
      covariates. The idea is to restrict the moment conditions to the ones that are
      only valid to certain types of time-dependent covariates. Our simulations show
      that efficiency on estimating regression parameters is achieved using modified
      approaches. Furthermore, we apply the modified approach to anthropometric
      screening data to evaluate the association between body mass index and morbidity
      in children in the Philippines.

PMID- 24723211
TI  - Myotoxicity of injections for acute muscle injuries: a systematic review.
AB  - BACKGROUND: Injection therapies are widely used for muscle injuries. As there is
      only limited evidence of their efficacy, physicians should be aware of the
      potential harmful effects of these injected preparations. OBJECTIVES: The purpose
      of this review was to systematically review the literature on the myotoxic
      effects of intramuscular injection preparations commonly used for acute muscle
      injuries. DATA SOURCES: The databases of PubMed, Embase, Web of Science, Cochrane
      Library, CINAHL and SportDiscus were searched in March 2013. STUDY ELIGIBILITY
      CRITERIA: Studies reporting histological evaluation or creatine kinase activity
      after intramuscular injection with local anaesthetics, corticosteroids, non
      steroidal anti-inflammatory drugs (NSAIDs), platelet-rich plasma (PRP),
      Traumeel((r)) and Actovegin((r)), or combination preparations were eligible for
      inclusion. DATA ANALYSIS: Two authors independently screened the search results
      and assessed the risk of bias. A best-evidence synthesis was used to identify the
      level of evidence. RESULTS: Forty-nine studies were included in this systematic
      review. There is strong to moderate evidence that intramuscularly injected local
      anaesthetics and NSAIDs are myotoxic, and there is conflicting evidence of the
      myotoxicity of PRP. There is limited evidence that single corticosteroid
      injections are not myotoxic but have a synergistic myotoxic effect when used
      together with local anaesthetics. There is no information to assess whether
      Actovegin((r)) and Traumeel((r)) are myotoxic. CONCLUSION: Local anaesthetics and
      NSAID injections are not recommended for the treatment of muscle injuries in
      athletes, as they are myotoxic. The possible myotoxic effects of corticosteroids,
      PRP, Traumeel((r)) and Actovegin((r)) should be assessed in future research.

PMID- 24723213
TI  - Reference intervals for plasma pro-gastrin releasing peptide (ProGRP) levels in
      healthy adults of Chinese Han ethnicity.
AB  - OBJECTIVES: To determine the upper limits of the 95th percentile reference
      intervals (RIs) for the detection of the pro-gastrin releasing peptide (ProGRP)
      in plasma according to the Clinical and Laboratory Standards Institute (CLSI) C28
      A3 guideline in a population of adult Chinese of Han ethnicity. METHODS: Plasma
      samples were collected from 578 healthy adults. Plasma ProGRP values were
      measured by chemiluminescent microparticle immunoassay (CMIA) on Abbot ARCHITECT
      i2000 system analyzers. RESULTS: Plasma ProGRP values did not conform to a
      Gaussian distribution, and thus non-parametric statistical methods were used to
      calculate RIs. Plasma ProGRP levels significantly increased with age, thus age
      dependent RIs were determined. The upper limit of the 95th percentile RIs for
      plasma ProGRP was <=57.26 pg/mL for young adults (18-50 years) and <=81.42 pg/mL
      for old adults (>50 years). CONCLUSIONS: By CMIA, we established distinct age
      dependent RIs for plasma ProGRP in healthy adults of Chinese Han ethnicity, thus
      generating a valuable reference for future clinical and laboratory studies.

PMID- 24723214
TI  - The impact of etomidate on mortality in trauma patients.
AB  - INTRODUCTION: Etomidate has a neutral hemodynamic profile which has made it an
      attractive medication for emergent intubation. Despite theoretical advantages of
      etomidate administration in the trauma patient, there are incomplete data to
      support its use. This study examined the association of etomidate use for
      emergent intubation in traumatic illness with patient mortality. METHODS: This is
      a historical cohort study using the Nova Scotia Trauma Registry. It included all
      major adult trauma patients who required tracheal intubation at the Queen
      Elizabeth II Health Sciences Centre in Halifax, Canada from January 23, 2000 to
      March 25, 2012. Prospectively recorded data were analyzed, including patient
      demographics, presence of comorbidities, trauma specific variables, admission and
      discharge vitals, length of stay in the intensive care unit (ICU) and hospital,
      mechanical ventilation-free days, and mortality. Associations between the use of
      etomidate and 28-day mortality are presented as odds ratios. Multivariable
      logistic regression models were created adjusting for age, injury severity score
      (ISS), sex, comorbidities, presence of traumatic brain injury, and injury type.
      The effects of etomidate on other relevant outcome variables were assessed using
      unpaired Student's t-tests. RESULTS: Three hundred eight patients were included
      in the study, and there were 42 deaths. Patients receiving etomidate were similar
      to those who did not, including ISS and pre-intubation blood pressure. The 28-day
      mortality was 18.7% in the etomidate group and 11.1% in the non-etomidate group
      (odds ratio = 1.85; 95% confidence interval [CI] 0.96 to 3.57; P = 0.07). After
      adjustment for age, female sex, ISS, and comorbidity, the odds ratio was 1.94
      (95% CI 0.87 to 4.37; P = 0.11). There were no differences between the two groups
      in ICU length of stay, hospital length of stay, or number of ventilation-free
      days. CONCLUSION: The association between use of a single dose of etomidate for
      emergency tracheal intubation in the trauma patient and mortality is
      inconclusive. Etomidate administration should be used with caution in trauma
      patients requiring tracheal intubation. Further data are required to determine
      the safety and risk-benefit of etomidate use in this patient population.

PMID- 24723215
TI  - Interaction of curcumin with manganese may compromise metal and neurotransmitter
      homeostasis in the hippocampus of young mice.
AB  - Manganese (Mn) exposure is related to industrial activities, where absorption by
      inhalation has high relevance. Manganism, a syndrome caused as a result of
      excessive accumulation of Mn in the central nervous system, has numerous symptoms
      similar to those seen in idiopathic Parkinson disease (IPD). Some of these
      symptoms, such as learning, memory, sensorial, and neurochemical changes, appear
      before the onset of motor deficits in both manganism and IPD. The aim of this
      study was to evaluate the possible neuroprotective effects of curcumin against
      behavioral deficits induced by Mn toxicity in young (2 months old) Swiss mice. We
      evaluated the effect of chronic inhalation of a Mn mixture [Mn(OAc)3 and MnCl2
      (20:40 mM)], 1 h/session, three times a week, over a 14-week period on behavioral
      and neurochemical parameters. Curcumin was supplemented in the diet (500 or 1,500
      ppm in food pellets). The Mn disrupted the motor performance evaluated in the
      single-pellet reach task, as well as the short- and long-term spatial memory
      evaluated in the step-down inhibitory avoidance task. Surprisingly, curcumin also
      produced similar deleterious effects in such behavioral tests. Moreover, the
      association of Mn plus curcumin significantly increased the levels of Mn and
      iron, and decreased the levels of dopamine and serotonin in the hippocampus.
      These alterations were not observed in the striatum. In conclusion, the current
      Mn treatment protocol resulted in mild deficits in motor and memory functions,
      resembling the early phases of IPD. Additionally, curcumin showed no beneficial
      effects against Mn-induced disruption of hippocampal metal and neurotransmitter
      homeostasis. 

PMID- 24723216
TI  - Possible effects of metallosis on spermatozoal apoptotic genes expression in
      individuals with intramedullary nailing prosthesis.
AB  - Seminal quality could be affected by metallosis caused by intramedullary nailing
      (IMN). Our objectives were to estimate metal ion levels in the seminal plasma of
      subjects with IMN, to determine their effects on semen parameters and on
      spermatozoal apoptotic gene expression, and to determine whether these expressed
      genes could be used as candidate biomarkers of seminal deterioration in
      individuals with IMN or not. Semen samples were collected from 60 subjects with
      IMN and 30 age-matched healthy controls. Seminal plasma contents of cobalt (Co),
      chromium (Cr), and molybdenum (Mo) were assayed. Spermatozoal Bcl-2 and Bax gene
      expressions were determined. Studied semen parameters were significantly lower in
      subjects with IMN for >=5 years in relation to controls while the concentrations
      of Co, Cr, and Mo in the seminal plasma samples were significantly higher. There
      were significantly lower spermatozoal Bcl-2 expression, higher Bax expression,
      and lower Bcl-2/Bax ratio in subjects with IMN for >=5 years than in controls. In
      subjects with IMN for >=5 years, receiver operating characteristic (ROC) curve
      analysis of studied gene expressions and Bcl-2/Bax ratio were done showing
      priority of the ratio with 86.7 % sensitivity, 100 % specificity, 100 % positive
      predictive value, and 93.8 % negative predictive value at cutoff values <=0.777.
      Co, Cr, and Mo metals are found at high concentrations in the seminal plasma of
      individuals with IMN leading to increased spermatozoal apoptotic activity.
      Spermatozoal Bcl-2/Bax ratio could be used as a candidate biomarker of
      reproductive disorders in individuals with intramedullary nailing. 

PMID- 24723217
TI  - The Ca, Cl, Mg, Na, and P mass fractions in human bone affected by Ewing's
      sarcoma.
AB  - The Ca, Cl, Mg, Na, and P contents and Ca/P, Ca/Mg, Ca/Na, Cl/Ca, and Cl/Na
      ratios in samples of intact bone, inflamed bone, and Ewing's sarcoma tissue were
      investigated by neutron activation analysis with high-resolution spectrometry of
      short-lived radionuclides. In Ewing's sarcoma tissue, the mass fractions of Cl
      and Na are higher and the mass fractions of Ca and Mg are lower than those of
      both normal and inflamed bone tissues. It was shown that the levels of Ca and Cl
      mass fractions and also levels of the Ca/Cl and Cl/Na ratios can be used as an
      additional test for differential diagnosis between inflamed (or normal) bone and
      Ewing's sarcoma. 

PMID- 24723218
TI  - Moderating factors for the effectiveness of group art therapy for schizophrenia:
      secondary analysis of data from the MATISSE randomised controlled trial.
AB  - PURPOSE: Although some studies suggest that art therapy may be useful in the
      treatment of negative symptoms of schizophrenia, a recent large trial of group
      art therapy found no clinical advantage over standard care, but the study
      population was heterogeneous and uptake of the intervention was poor. This study
      aimed to investigate whether art therapy was more effective for specific
      subgroups of patients. METHODS: Secondary analysis of data from a randomised
      controlled trial of group art therapy as an adjunctive treatment for
      schizophrenia (n = 140) versus standard care alone (n = 137). Positive and
      Negative Syndrome Scale scores at 12 months were compared between trial arms.
      Interaction between intervention effect and different subgroups, including those
      with more severe negative symptoms of schizophrenia, and those who expressed a
      preference for art therapy prior to randomisation, was tested using a linear
      mixed model. RESULTS: The clinical effectiveness of group art therapy did not
      significantly differ between participants with more or less severe negative
      symptoms [interaction for difference in PANSS = 1.7, 95 % CI (-8.6 to 12.1), P =
      0.741], or between those who did and did not express a preference for art therapy
      [interaction = 3.9, 95 % CI (-6.7 to 14.5), P = 0.473]. None of the other
      exploratory subgroups suggested differences in intervention effect. CONCLUSIONS:
      There was no evidence of greater improvement in clinical symptoms of
      schizophrenia for those with more severe negative symptoms or those with a
      preference for art therapy. Identification of patients with schizophrenia who may
      benefit most from group art therapy remains elusive.

PMID- 24723220
TI  - Level of thyroid-stimulating hormone (TSH) in patients with acute schizophrenia,
      unipolar depression or bipolar disorder.
AB  - The aim of this study is to investigate differences in thyroid-stimulating
      hormone (TSH) level in patients with acute schizophrenia, unipolar depression,
      bipolar depression and bipolar mania. Serum level of TSH was measured in 1,685
      Caucasian patients (1,064 women, 63.1%; mean age 46.4). Mean serum TSH
      concentration was: schizophrenia (n = 769) 1.71 MUIU/mL, unipolar depression (n =
      651) 1.63 MUIU/mL, bipolar disorder (n = 264) 1.86 MUIU/mL, bipolar depression (n
      = 203) 2.00 MUIU/mL, bipolar mania (n = 61) 1.38 MUIU/mL (H = 11.58, p = 0.009).
      Depending on the normal range used, the overall rate of being above or below the
      normal range was 7.9-22.3% for schizophrenia, 13.9-26.0% for unipolar depression,
      10.8-27.6% for bipolar disorder, 12.2-28.5% for bipolar depression, and 11.4
      24.5% for bipolar mania. We have also found differences in TSH levels between the
      age groups (<=20, >20 years and <=40, >40 years and <=60 years and >60 years).
      TSH level was negatively correlated with age (r = -0.23, p < 0.001). Weak
      correlations with age have been found in the schizophrenia (r = -0.21, p <
      0.001), unipolar depression (r = -0.23, p < 0.001), bipolar depression (r = 
      0.25, p = 0.002) and bipolar disorder (r = -0.21, p = 0.005) groups. Our results
      confirm that there may be a higher prevalence of thyroid dysfunctions in patients
      with mood disorders (both unipolar and bipolar) and that these two diagnostic
      groups differ in terms of direction and frequency of thyroid dysfunctions.

PMID- 24723219
TI  - Dielectrophoretic isolation and detection of cancer-related circulating cell-free
      DNA biomarkers from blood and plasma.
AB  - Conventional methods for the isolation of cancer-related circulating cell-free
      (ccf) DNA from patient blood (plasma) are time consuming and laborious. A DEP
      approach utilizing a microarray device now allows rapid isolation of ccf-DNA
      directly from a small volume of unprocessed blood. In this study, the DEP device
      is used to compare the ccf-DNA isolated directly from whole blood and plasma from
      11 chronic lymphocytic leukemia (CLL) patients and one normal individual. Ccf-DNA
      from both blood and plasma samples was separated into DEP high-field regions,
      after which cells (blood), proteins, and other biomolecules were removed by a
      fluidic wash. The concentrated ccf-DNA was detected on-chip by fluorescence, and
      then eluted for PCR and DNA sequencing. The complete process from blood to PCR
      required less than 10 min; an additional 15 min was required to obtain plasma
      from whole blood. Ccf-DNA from the equivalent of 5 MUL of CLL blood and 5 MUL of
      plasma was amplified by PCR using Ig heavy-chain variable (IGHV) specific primers
      to identify the unique IGHV gene expressed by the leukemic B-cell clone. The PCR
      and DNA sequencing results obtained by DEP from all 11 CLL blood samples and from
      8 of the 11 CLL plasma samples were exactly comparable to the DNA sequencing
      results obtained from genomic DNA isolated from CLL patient leukemic B cells
      (gold standard).

PMID- 24723221
TI  - Selective synthesis of (Z)-2-enynyl-2-hydroxy-imidazolidine-4,5-diones via Cu(I)
      mediated multicomponent coupling of terminal alkynes, carbodiimides and oxalyl
      chloride.
AB  - (Z)-2-Enynyl-2-hydroxy-imidazolidine-4,5-diones 2 are synthesized for the first
      time via Cu(I)-mediated (Z)-selective geminal coupling among two molecules of
      terminal alkynes, carbodiimides, and oxalyl chloride. Further transformation of
      2a is performed to yield a highly functionalized spiro heterocyclic compound 5.

PMID- 24723222
TI  - The Knickkopf DOMON domain is essential for cuticle differentiation in Drosophila
      melanogaster.
AB  - The dopamine monoxygenase N-terminal (DOMON) domain is found in extracellular
      proteins across several eukaryotic and prokaryotic taxa. It has been proposed
      that this domain binds to heme or sugar moieties. Here, we have analyzed the role
      of four highly conserved amino acids in the DOMON domain of the Drosophila
      melanogaster Knickkopf protein that is inserted into the apical plasma membrane
      and assists extracellular chitin organization. In principal, we generated
      Knickkopf versions with exchanged residues tryptophan(299), methionine(333),
      arginine(401), or histidine(437), and scored for the ability of the respective
      engineered protein to normalize the knickkopf mutant phenotype. Our results
      confirm the absolute necessity of tryptophan(299), methionine(333), and
      histidine(437) for Knickkopf function and stability, the latter two being
      predicted to be critical for heme binding. In contrast, arginine(401) is required
      for full efficiency of Knickkopf activity. Taken together, our genetic data
      support the prediction of these residues to mediate the function of Knickkopf
      during cuticle differentiation in insects. Hence, the DOMON domain is apparently
      an essential factor contributing to the construction of polysaccharide-based
      extracellular matrices.

PMID- 24723223
TI  - Suppression of Dicer increases sensitivity to gefitinib in human lung cancer
      cells.
AB  - BACKGROUND: Accumulating evidence is revealing an important role of microRNA
      (miRNA) in tumor progression and chemotherapeutic resistance. Dicer is a
      cytoplasmic endoribonuclease type III crucial for production of mature miRNAs.
      The aberrant expression of Dicer has also been reportedly associated with
      clinical aggressiveness, prognosis, and patient survival in various cancer types.
      However, the molecular mechanisms of Dicer in acquired gefitinib resistance are
      still not clear. METHODS: In this study, we analyzed the protein level of Dicer
      between gefitinib-sensitive (PC9) and gefitinib-resistant (PC9/GR) non-small-cell
      lung cancer (NSCLC) cell lines by Western blot analysis. Silence and
      overexpression of the Dicer were performed to investigate the effects on
      gefitinib sensitivity, as assessed by (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl
      tetrazolium bromide) assay and sub-G1 assay of flow cytometry. To further explore
      the mechanism of chemoresistance, we examined whether Dicer knockdown led to
      modulating specific miRNAs and its miRNA target genes. RESULTS: Dicer expression
      was significantly increased in PC9/GR compared with PC9 cells. Knockdown of Dicer
      restores gefitinib sensitivity in resistant cells, and overexpression of Dicer
      enhances resistance to gefitinib in sensitive cells. Silencing of Dicer induces
      sensitivity to gefitinib in NSCLC cells through the downregulation of miR-30b/c
      and miR-221/222 to increase the protein level of caspase-3, resulting in an
      increase in gefitinib-induced apoptosis. CONCLUSIONS: Dicer contributes to the
      resistance to gefitinib in lung cancer. These results indicate that Dicer may be
      a target for diagnosis and therapy of patients with resistance to gefitinib.

PMID- 24723224
TI  - Conservative hepatectomy for tumors involving the middle hepatic vein and segment
      1: the liver tunnel.
AB  - BACKGROUND: For lesions invading the middle hepatic vein (MHV) at caval
      confluence (CC) the mini-mesohepatectomy(MMH) was proposed.1 If the lesion is
      extended to the paracaval portion of segment 1(S1) in contact or invading the MHV
      a new procedure is proposed. METHODS: Case-1: mass forming cholangiocarcinoma
      (MFCCC) 4cm in size invading the MHV and in contact with right (RHV) and left
      hepatic vein (LHV) at the CC. In Case-2, two colorectal liver metastases (CLM)
      both 2cm in size occupied S1 (T1) and S8 (T2): T1 was located between RHV and the
      inferior vena cava (IVC), T2 was in contact with MHV at CC. According to tumor
      vessel intraoperative-ultrasound classification2 and color-flow analysis3
      parenchyma-sparing procedure was performed. RESULTS: In Case-1 a communicating
      vein (CV) between RHV and MHV was detected at color-flow-IOUS. Contacts between
      MFCCC with RHV and LHV were confirmed at IOUS as detachable. In Case-2 contact
      between T1 with MHV was confirmed at IOUS as detachable. Liver-tunnel with IVC
      and main portal vein bifurcation exposure was performed resecting the MHV in Case
      1 and preserving it in Case-2. Both patients had ad an uneventful postoperative
      course and were discharged on the 8th postoperative day. CONCLUSION: For tumors
      involving S1, S4s and/or S8 and infiltrating or in contact with the MHV at the
      CC, can be removed in a conservative manner by means of the herein described
      ''Liver Tunnel'' approach. The latter introduces a further step in favour of
      parenchyma-sparing policy for centrally located lesions with complex tumor-vessel
      relationship.

PMID- 24723225
TI  - Incidence patterns of primary bone cancer in taiwan (2003-2010): a population
      based study.
AB  - BACKGROUND: Primary bone cancer (BC) incidence by age has not been surveyed in
      Asia. METHODS: The incidence patterns of nine subtypes of primary BCs registered
      between 2003 and 2010 were analyzed from Taiwan cancer registry data. More
      specific analyses were conducted within age groups (Group I: 0-24 years; Group
      II: 25-59 years; and Group III: 60-85+ years). RESULTS: A total of 1,238 newly
      diagnosed subjects were registered with an age-standardized incidence rate (ASR)
      of 6.70 per million person-years. Overall, osteosarcoma (OS: 45 %) was the most
      common, followed by chondrosarcoma (CS: 18 %), and Ewing sarcoma (ES: 8 %). The
      percentages of cases and ASRs for age groups I, II, and III were 36.3, 43.0, and
      20.7 %, and 7.00, 5.48, and 10.28 per million, respectively. Significant male
      predilections were observed for all BCs combined, and the CS, chordoma, and
      malignant ameloblastoma subtypes. Our findings demonstrated an upward trend of
      4.8 % per year over the study period, and was more significant for females (6.7
      %). A significant increase in trend existed in the incidence of BC among females
      in Group II, and the incidence of OS and ES among females in Group I.
      CONCLUSIONS: This population-based study has allowed us to confidently define the
      incidence rates among three age groups of Taiwanese. Despite overall low rates,
      the upward trend in BC incidence among females may invoke a concern. The results
      suggest areas for further study into the underlying causes for these cancer
      trends.

PMID- 24723227
TI  - Curcumin analogue UBS109 prevents bone loss in breast cancer bone metastasis
      mouse model: involvement in osteoblastogenesis and osteoclastogenesis.
AB  - Bone metastasis of breast cancer typically leads to osteolysis, which causes
      severe pathological bone fractures and hypercalcemia. Bone homeostasis is
      skillfully regulated through osteoblasts and osteoclasts. Bone loss with bone
      metastasis of breast cancer may be due to both activation of osteoclastic bone
      resorption and suppression of osteoblastic bone formation. This study was
      undertaken to determine whether the novel curcumin analogue UBS109 has preventive
      effects on bone loss induced by breast cancer cell bone metastasis. Nude mice
      were inoculated with breast cancer MDA-MB-231 bone metastatic cells (10(6)
      cells/mouse) into the head of the right and left tibia. One week after
      inoculation, the mice were treated with control (vehicle), oral administration
      (p.o.) of UBS109 (50 or 150 mg/kg body weight), or intraperitoneal administration
      (i.p.) of UBS109 (10 or 20 mg/kg body weight) once daily for 5 days per week for
      7 weeks. After UBS109 administration for 7 weeks, hind limbs were assessed using
      an X-ray diagnosis system and hematoxylin and eosion staining to determine
      osteolytic destruction. Bone marrow cells obtained from the femurs and tibias
      were cultured to estimate osteoblastic mineralization and osteoclastogenesis ex
      vivo and in vitro. Remarkable bone loss was demonstrated in the tibias of mice
      inoculated with breast cancer MDA-MB-231 bone metastatic cells. This bone loss
      was prevented by p.o. administration of UBS109 (50 and 150 mg/kg body weight) and
      i.p. treatment of UBS109 (10 and 20 mg/kg) in vivo. Culture of bone marrow cells
      obtained from the bone tissues of mice with breast cancer cell bone metastasis
      showed suppressed osteoblastic mineralization and stimulated osteoclastogenesis
      ex vivo. These changes were not seen after culture of the bone marrow cells
      obtained from mice treated with UBS109. Moreover, UBS109 was found to stimulate
      osteoblastic mineralization and suppress lipopolysaccharide (LPS)-induced
      osteoclastogenesis in bone marrow cells obtained from normal nude mice in vitro.
      These findings suggest that the novel curcumin analogue UBS109 prevents breast
      cancer cell bone metastasis-induced bone loss by stimulating osteoblastic
      mineralization and suppressing osteoclastogenesis. 

PMID- 24723228
TI  - Calcium signaling and epilepsy.
AB  - Calcium signaling is involved in a multitude of physiological and
      pathophysiological mechanisms. Over the last decade, it has been increasingly
      recognized as an important factor in epileptogenesis, and it is becoming obvious
      that the excess synchronization of neurons that is characteristic for seizures
      can be linked to various calcium signaling pathways. These include immediate
      effects on membrane excitability by calcium influx through ion channels as well
      as delayed mechanisms that act through G-protein coupled pathways. Calcium
      signaling is able to cause hyperexcitability either by direct modulation of
      neuronal activity or indirectly through calcium-dependent gliotransmission.
      Furthermore, feedback mechanisms between mitochondrial calcium signaling and
      reactive oxygen species are able to cause neuronal cell death and seizures.
      Unravelling the complexity of calcium signaling in epileptogenesis is a daunting
      task, but it includes the promise to uncover formerly unknown targets for the
      development of new antiepileptic drugs. 

PMID- 24723229
TI  - Impact of aging on heat shock protein expression in the substantia nigra and
      striatum of the female rat.
AB  - Many heat shock proteins are chaperones that help refold or degrade misfolded
      proteins and battle apoptosis. Because of their capacity to protect against
      protein misfolding, they may help keep diseases of aging at bay. A few reports
      have examined heat shock proteins (eg. Hsp25, Hsp60, Hsp70, and heat shock
      cognate 70 or Hsc70) as a function of age in the striatum and nigra. In the
      present study, we examined the impact of aging on Hsp25, heme oxygenase 1 (HO1 or
      Hsp32), Hsp40, Hsp60, Hsc70, Hsc/Hsp70 interacting protein (Hip), 78 kDa glucose
      regulated protein (GRP78), Hsp90, and ubiquitinated proteins in the nigra and
      striatum of the female rat by infrared immunoblotting. Female animals are not
      typically examined in aging studies, adding further to the novelty of our study.
      Striatal HO1 and Hsp40 were both higher in middle-aged females than in the oldest
      group. Hsp60 levels were also highest in middle age in the nigra, but were
      highest in the oldest animals in the striatum. Striatal levels of Hsc70 and the
      co-chaperone Hip were lower in the oldest group relative to the youngest animals.
      In contrast, Hsp25 rose with advancing age in both regions. Hsp25 was also
      colocalized with tyrosine hydroxylase in nigral neurons. Ubiquitinated proteins
      exhibited a trend to rise in the oldest animals in both regions, and K48 linkage
      specific ubiquitin rose significantly from 4-6 to 16-19 months in the striatum.
      Our study reveals a complex array of age-related changes in heat shock proteins.
      Furthermore, the age-related rises in some proteins, such as Hsp25, may reflect
      endogenous adaptations to cellular stress. 

PMID- 24723230
TI  - Fibrosis and inflammation are greater in muscles of beta-sarcoglycan-null mouse
      than mdx mouse.
AB  - The Sgcb-null mouse, with knocked-down beta-sarcoglycan, develops severe muscular
      dystrophy as in type 2E human limb girdle muscular dystrophy. The mdx mouse,
      lacking dystrophin, is the most used model for Duchenne muscular dystrophy (DMD).
      Unlike DMD, the mdx mouse has mild clinical features and shows little fibrosis in
      limb muscles. To characterize ECM protein deposition and the progression of
      muscle fibrosis, we evaluated protein and transcript levels of collagens I, III
      and VI, decorin, and TGF-beta1, in quadriceps and diaphragm, at 2, 4, 8, 12, 26,
      and 52 weeks in Sgcb-null mice, and protein levels at 12, 26, and 52 weeks in mdx
      mice. In Sgcb-null mice, severe morphological disruption was present from 4 weeks
      in both quadriceps and diaphragm, and included conspicuous deposition of
      extracellular matrix components. Histopathological features of Sgcb-null mouse
      muscles were similar to those of age-matched mdx muscles at all ages examined,
      but, in the Sgcb-null mouse, the extent of connective tissue deposition was
      generally greater than mdx. Furthermore, in the Sgcb-null mouse, the amount of
      all three collagen isoforms increased steadily, while, in the mdx, they remained
      stable. We also found that, at 12 weeks, macrophages were significantly more
      numerous in mildly inflamed areas of Sgcb-null quadriceps compared to mdx
      quadriceps (but not in highly inflamed regions), while, in the diaphragm,
      macrophages did not differ significantly between the two models, in either
      region. Osteopontin mRNA was also significantly greater at 12 weeks in laser
      dissected highly inflamed areas of the Sgcb-null quadriceps compared to the mdx
      quadriceps. TGF-beta1 was present in areas of degeneration-regeneration, but
      levels were highly variable and in general did not differ significantly between
      the two models and controls. The roles of the various subtypes of macrophages in
      muscle repair and fibrosis in the two models require further study. The Sgcb-null
      mouse, which develops early fibrosis in limb muscles, appears more promising than
      the mdx mouse for probing pathogenetic mechanisms of muscle fibrosis and for
      developing anti-fibrotic treatments. Highlights * The Sgcb-null mouse develops
      severe muscular dystrophy, the mdx mouse does not. * Fibrosis developed earlier
      in Sgcb-null quadriceps and diaphragm than mdx. * Macrophages were commoner in
      mildly inflamed parts of Sgcb-null quadriceps than mdx. * The Sgcb-null model
      appears more useful than mdx for studying fibrotic mechanisms. * The Sgcb-null
      model also appears more useful for developing anti-fibrotic treatments.

PMID- 24723231
TI  - Correlation between three-dimensional ultrasound features and pathological
      prognostic factors in breast cancer.
AB  - OBJECTIVES: To investigate the correlation of three-dimensional (3D) ultrasound
      features with prognostic factors in invasive ductal carcinoma. METHODS: Surgical
      resection specimens of 85 invasive ductal carcinomas of 85 women who had
      undergone 3D ultrasound were included. Morphology features and vascularization
      perfusion on 3D ultrasound were evaluated. Pathologic prognostic factors,
      including tumour size, histological grade, lymph node status, oestrogen and
      progesterone receptor status (ER, PR), c-erbB-2 and p53 expression, and
      microvessel density (MVD) were determined. Correlations of 3D ultrasound features
      and prognostic factors were analysed. RESULTS: The retraction pattern in the
      coronal plane had a significant value as an independent predictor of a small
      tumour size (P = 0.014), a lower histological grade (P = 0.009) and positive ER
      or PR expression status (P = 0.001, 0.044). The retraction pattern with a
      hyperechoic ring only existed in low-grade and ER-positive tumours. The presence
      of the hyperechoic ring strengthened the ability of the retraction pattern to
      predict a good prognosis of breast cancer. The increased intra-tumour
      vascularization index (VI, the mean tumour vascularity) reflected a higher
      histological grade (P = 0.025) and had a positive correlation with MVD (r =
      0.530, P = 0.001). CONCLUSIONS: The retraction pattern and histogram indices of
      VI provided by 3D ultrasound may be useful in predicting prognostic information
      about breast cancer. KEY POINTS: Three-dimensional ultrasound can potentially
      provide prognostic evaluation of breast cancer. The retraction pattern and
      hyperechoic ring in the coronal plane suggest good prognosis. The increased intra
      tumour vascularization index reflects a higher histological grade. The intra
      tumour vascularization index is positively correlated with microvessel density.

PMID- 24723232
TI  - Magnetic resonance-derived circumferential strain provides a superior and
      incremental assessment of improvement in contractile function in patients early
      after ST-segment elevation myocardial infarction.
AB  - BACKGROUND: We evaluate whether circumferential strain derived from grid-tagged
      CMR is a better method for assessing improvement in segmental contractile
      function after STEMI compared to late gadolinium enhancement (LGE). METHODS:
      STEMI patients post primary PCI underwent baseline CMR (day 3) and follow-up (day
      90). Cine, grid-tagged and LGE images were acquired. Baseline LGE infarct
      hyperenhancement was categorised as <=25 %, 26-50 %, 51-75 % and >75 %
      hyperenhancement. The segmental baseline circumferential strain (CS) and
      circumferential strain rate (CSR) were calculated from grid-tagged images.
      Segments demonstrating an improvement in wall motion of >=1 grade compared to
      baseline were regarded as having improved segmental contractile-function.
      RESULTS: Forty-five patients (aged 58 +/- 12 years) and 179 infarct segments were
      analysed. A baseline CS cutoff of -5 % had sensitivity of 89 % and specificity of
      70 % for detection of improvement in segmental-contractile-function. On receiver
      operating characteristic analysis for predicting improvement in contractile
      function, AUC for baseline CS (0.82) compared favourably to LGE hyperenhancement
      (0.68), MVO (0.67) and baseline-CSR (0.74). On comparison of AUCs, baseline CS
      was superior to LGE hyperenhancement and MVO in predicting improvement in
      contractile function (P < 0.001). On multivariate-analysis, baseline CS was the
      independent predictor of improvement in segmental contractile function (P <
      0.001). CONCLUSION: Grid-tagged CMR-derived baseline CS is a superior predictor
      of improvement in segmental contractile function, providing incremental value
      when added to LGE hyperenhancement and MVO following STEMI. KEY POINTS: Baseline
      CS predicts contractile function recovery better than LGE and MVO following
      STEMI. Baseline CS predicts contractile function recovery better than baseline
      CSR following STEMI. Baseline CS provides incremental value to LGE and MVO
      following STEMI.

PMID- 24723234
TI  - Adherence to cancer prevention guidelines and risk of breast cancer.
AB  - Healthy eating patterns and keeping physically active are potentially more
      important for chronic disease prevention than intake or exclusion of specific
      food items or nutrients. To this end, many health organizations routinely publish
      dietary and lifestyle recommendations aimed at preventing chronic disease. Using
      data from the Canadian National Breast Screening Study, we investigated the
      association between breast cancer risk and adherence to two sets of guidelines
      specific for cancer prevention, namely the American Cancer Society (ACS)
      Guidelines and the World Cancer Research Fund/American Institute for Cancer
      Research (WCRF/AICR) Recommendations. At baseline, 49,613 women completed dietary
      and lifestyle questionnaires and height and weight measurements were taken.
      During a mean follow-up of 16.6 years, 2,503 incident cases of breast cancer were
      ascertained. Cox proportional hazard models were used to estimate hazard ratios
      (HR) and 95% confidence intervals (CI) for the association of meeting each
      guideline, and number of guidelines met, with breast cancer risk. The two sets of
      guidelines yielded similar results. Specifically, adherence to all six ACS
      guidelines was associated with a 31% reduction in breast cancer risk when
      compared to subjects adhering to at most one guideline (HR=0.69; 95% CI=0.49
      0.97); similarly, adherence to six or seven of the WCRF/AICR guidelines was also
      associated with a 31% reduction in breast cancer risk (HR=0.69; 95% CI=0.47
      1.00). Under either classification, meeting each additional guideline was
      associated with a 4-6% reduction in breast cancer risk. These results suggest
      that adherence to cancer prevention guidelines is associated with a reduced risk
      of breast cancer.

PMID- 24723233
TI  - Pathological and biochemical studies of mucopolysaccharidosis type IIIB
      (Sanfilippo syndrome type B) in juvenile emus (Dromaius novaehollandiae).
AB  - Mucopolysaccharidosis (MPS) type IIIB was diagnosed in 14 juvenile emus (Dromaius
      novaehollandiae), ages 3 weeks to 6 months, based on pathological and biochemical
      analyses. The animals had a history of neurological signs or sudden death; one of
      the birds with neurological signs and 3 others experienced acute hemoabdomen.
      Histopathologically, neuronal swelling and vacuolation in the cerebrum,
      cerebellum, brainstem, and spinal cord (80%-92%); retina (100%); autonomic
      ganglia of the intestine (71%); gizzard (50%); adrenal gland (27%); and ear (50%)
      were noted in affected but not healthy emus. Cytoplasmic vacuoles were also
      observed in the pancreas, liver, intestine, adrenal glands, and kidneys. The
      intracytoplasmic inclusions were periodic acid-Schiff and Luxol Fast Blue
      positive, consistent with a storage disease. Foamy macrophages infiltrated the
      liver, intestine, tunica media of the aorta, and spleen. By transmission electron
      microscopy, typical lamellated cytoplasmic bodies were detected in neurons of the
      brain and retina, while electron-dense bodies consistent with glycosaminoglycan
      inclusions were observed in hepatocytes and/or hepatic macrophages. The livers of
      the 2 affected emus studied contained large amounts of heparan sulfate, which is
      suggestive of MPS type III. Compared with normal controls, hepatic and serum
      alpha-N-acetylglucosaminidase activity was very low (<8% of control), while other
      enzyme activities were normal to increased in the 2 affected emus studied.
      Moreover, affected emus were homozygous for a 2-bp deletion in the NAGLU gene.
      This study characterizes the pathology of MPS type IIIB in emus, which is one of
      the rare inborn errors in birds, showing the homology of this condition to
      Sanfilippo syndrome in humans. 

PMID- 24723235
TI  - Biotoxin sensing in food and environment via microchip.
AB  - Biotoxin contamination in food and environmental samples has threatened health or
      life of human and animals. Thus, a rapid lab-independent sensing method for
      biotoxin determination is urgently required. Microchip sensing system allows a
      promising rapid and low-cost detection strategy. Herein, the recent development
      of various microchips, including microfluidic chip and microarray, has been
      discussed to sense various biotoxins in food and environmental samples (i.e.
      phytotoxin, animal toxin, marine toxin, and mycotoxin). Microchip can be served
      as both analyte transportation and sensing platform, via either labeling or
      labeling-free sensing strategy. Because of its fast sensing time, low sample
      consumption, ready portability, and high compatibility, it has been extensively
      employed in biotoxin determination in both academic and industrial circle. With
      the advances of fabrication strategies and sensing modes, the microchip
      performance has been dramatically improved, including sensitivity, efficiency,
      reliability, stability, cost saving, portability. The potential applications can
      be found wide spread in biotoxin sensing in the near future, while their
      practical application in real sample need to be addressed. 

PMID- 24723236
TI  - Angioedema in pediatric heart transplant recipients-reporting C1-esterase
      inhibitor deficiency without analysing protein.

PMID- 24723237
TI  - Post-contrast T1-weighted sequences in pediatric abdominal imaging: comparative
      analysis of three different sequences and imaging approach.
AB  - BACKGROUND: Post-contrast T1-weighted imaging is an essential component of a
      comprehensive pediatric abdominopelvic MR examination. However, consistent good
      image quality is challenging, as respiratory motion in sedated children can
      substantially degrade the image quality. OBJECTIVE: To compare the image quality
      of three different post-contrast T1-weighted imaging techniques-standard three
      dimensional gradient-echo (3-D-GRE), magnetization-prepared gradient-recall echo
      (MP-GRE) and 3-D-GRE with radial data sampling (radial 3-D-GRE)-acquired in
      pediatric patients younger than 5 years of age. MATERIALS AND METHODS: Sixty
      consecutive exams performed in 51 patients (23 females, 28 males; mean age 2.5 +/
      1.4 years) constituted the final study population. Thirty-nine scans were
      performed at 3 T and 21 scans were performed at 1.5 T. Two different reviewers
      independently and blindly qualitatively evaluated all sequences to determine
      image quality and extent of artifacts. RESULTS: MP-GRE and radial 3-D-GRE
      sequences had the least respiratory motion (P < 0.0001). Standard 3-D-GRE
      sequences displayed the lowest average score ratings in hepatic and pancreatic
      edge definition, hepatic vessel clarity and overall image quality. Radial 3-D-GRE
      sequences showed the highest scores ratings in overall image quality.
      CONCLUSIONS: Our preliminary results support the preference of fat-suppressed
      radial 3-D-GRE as the best post-contrast T1-weighted imaging approach for
      patients under the age of 5 years, when dynamic imaging is not essential.

PMID- 24723238
TI  - Protein expression of urate transporters in renal tissue of patients with uric
      acid nephrolithiasis.
AB  - URAT1 and GLUT9 are two primary urate transporters involved in the renal urate
      handling. Renal urate underexcretion was reported in uric acid stone formers
      (UASF) in previous clinical studies. The aim of this study was to investigate the
      clinical features and possible impact of protein expression of URAT1 and GLUT9 in
      renal tissues of patients with uric acid (UA) nephrolithiasis. 23 UASF, 27
      patients with calcium oxalate (CaOx) stones, and 22 normal controls were enrolled
      in this study. Clinical data revealed that older age of onset, high plasma UA
      concentration, low urinary PH, and relative renal urate underexcretion were
      associated with UASF. By immunohistochemical or western blotting analysis, a
      significant increase in the relative expression quantity of URAT1 in renal tissue
      of UASF was found compared to patients with CaOx nephrolithiasis and normal
      controls. In conclusion, our results suggested that upregulated URAT1 protein
      expression might contribute to the relative urate underexcretion from the kidney
      of UASF.

PMID- 24723239
TI  - An in vitro assessment of fluoride uptake by tooth enamel from four different
      fluoride dentifrices.
AB  - AIM: The aim of this study was to evaluate fluoride uptake by tooth enamel with
      four different fluoride dentifrices. STUDY DESIGN: Sixty human premolars
      extracted for orthodontic purpose were selected for the study. The teeth were
      covered with nail varnish leaving a window of 4 * 4 mm on the enamel surface of
      the buccal and lingual sides. The teeth were demineralised and were divided into
      four groups with 15 teeth in each group. The buccal window served as experimental
      and the lingual as control. The teeth were immersed in toothpaste slurry
      containing: sodium fluoride (Group A); sodium monofluorophosphate (Group B);
      stannous fluoride (Group C) and amine fluoride (Group D). The fluoride content in
      the etched superficial enamel layer in the windows was analysed using a fluoride
      ion-specific electrode. RESULTS: Within the parameters of this study, the uptake
      of fluoride was statistically significant in Group D (p < 0.05). The uptake of
      fluoride by tooth enamel in an increasing order was Group A < Group B < Group C <
      Group D. CONCLUSION: The study showed that enamel treated with amine fluoride had
      the highest fluoride uptake.

PMID- 24723240
TI  - A comparative study of single incision versus conventional laparoscopic inguinal
      hernia repair.
AB  - BACKGROUND: Over the past years, safety and feasibility of conventional
      laparoscopic inguinal hernia repair was well established. However, conventional
      laparoscopic hernia repair (CL) usually requires three working ports ranging from
      5 to 10 mm, and each increasing port is associated with possible increasing
      morbidity and pain related to ports. This has led to the development of single
      incision laparoscopic hernia repair (SIL) which can further reduce the port
      related morbidities and improve cosmetic outcomes. The aim of the study was to
      evaluate the safety and feasibility of SIL using both transabdominal
      preperitoneal (TAPP) and totally preperitoneal (TEP) approaches and compare the
      patients' wound satisfaction between the two groups. METHODS: This is a
      retrospective review of prospectively collected data. We analyzed the results of
      patients who underwent either CL or SIL for inguinal hernia between January 2011
      and July 2012 in Pamela Youde Nethersole Eastern Hospital. Patients' demographic
      details, type of hernia, operative time, mesh used, and post-operative
      complications were compared. A telephone survey was also conducted to evaluate
      patients' subjective wound satisfaction. RESULTS: In total, 32 SIL and 35 CL
      procedures were performed in this period. The two groups were matched for age,
      sex, type of hernia and ASA grading. The mean operative time was significantly
      shorter in the CL group (52.6 vs. 62.6 min, p = 0.02). All SIL procedures were
      completed successfully without conversion to CL or open repair and post-operative
      complications such as wound infection, seroma, recurrence and chronic pain were
      also comparable between the two groups. As for the telephone survey, SIL groups'
      wound is less obvious and less detectable by others as compared to CL, but on the
      whole both groups of patients are very satisfied with the wound outcomes. All the
      SIL groups would continue with their decision on SIL and 60 % of CL group would
      choose SIL if they had to go back in time. CONCLUSION: Our results have shown
      that in experienced hands, SIL is feasible and as safe as CL. Further randomized
      trials should be performed to evaluate the clinical application of single
      incision TEP and TAPP.

PMID- 24723241
TI  - High LET (56)Fe ion irradiation induces tissue-specific changes in DNA
      methylation in the mouse.
AB  - DNA methylation is an epigenetic mechanism that drives phenotype and that can be
      altered by environmental exposures including radiation. The majority of human
      radiation exposures occur in a relatively low dose range; however, the biological
      response to low dose radiation is poorly understood. Based on previous
      observations, we hypothesized that in vivo changes in DNA methylation would be
      observed in mice following exposure to doses of high linear energy transfer (LET)
      (56) Fe ion radiation between 10 and 100 cGy. We evaluated the DNA methylation
      status of genes for which expression can be regulated by methylation and that
      play significant roles in radiation responses or carcinogenic processes including
      apoptosis, metastasis, cell cycle regulation, and DNA repair (DAPK1, EVL, 14.3.3,
      p16, MGMT, and IGFBP3). We also evaluated DNA methylation of repeat elements in
      the genome that are typically highly methylated. No changes in liver DNA
      methylation were observed. Although no change in DNA methylation was observed for
      the repeat elements in the lungs of these same mice, significant changes were
      observed for the genes of interest as a direct effect and a delayed effect of
      irradiation 1, 7, 30, and 120 days post exposure. At delayed times, differences
      in methylation profiles among genes were observed. DNA methylation profiles also
      significantly differed based on dose, with the lowest dose frequently affecting
      the largest change. The results of this study are the first to demonstrate in
      vivo high LET radiation-induced changes in DNA methylation that are tissue and
      locus specific, and dose and time dependent.

PMID- 24723243
TI  - A multidisciplinary approach to evaluate the efficiency of a clean-up technology
      to remove mercury from water.
AB  - A microporous material denoted ETS-4 was used as the decontaminant agent to treat
      water with a low level of Hg contamination. The effectiveness of the treatment
      was evaluated by assessment of the efficiency of Hg removal and ecotoxicological
      responses. The results showed that under highly competitive conditions the
      removal of Hg ranged between 58 % and 73 % depending upon the initial Hg
      concentration, and that Hg removal was reflected in decreased toxicity to some
      organisms. The ecotoxicological data indicated that the bacterium Vibrio fischeri
      was the least sensitive organism tested, as no toxicity was observed in either
      pre- or post-treatment waters. Daphnia magna was highly sensitive to Hg. Mercury
      removal by ETS-4 was not sufficient to completely remove the toxicity of Hg to D.
      magna. However, it was effective in the complete reduction of toxicity for the
      green alga, Pseudokirchneriella subcapitata.

PMID- 24723244
TI  - Water-fat separation in diffusion-weighted EPI using an IDEAL approach with image
      navigator.
AB  - PURPOSE: Echo planar-based diffusion-weighted MRI (DW-MRI) requires robust
      suppression of fat signal. Fat suppression techniques such as inversion recovery
      or spectrally selective excitation with subsequent gradient spoiling can extend
      scan time or perform suboptimally in the presence of strong main field
      inhomogeneities. Chemical shift-encoded water-fat separation using iterative
      decomposition of water and fat with echo asymmetry and least-squares estimation
      (IDEAL) is robust in areas of main field inhomogeneity but requires accurate
      phase information, which can be distorted by patient motion during diffusion
      weighting gradients. A method is proposed to overcome this with the use of image
      navigators. THEORY AND METHODS: A spin echo planar imaging (SE-EPI) diffusion
      weighted sequence was modified to incorporate IDEAL acquisition in combination
      with an image navigator to correct for patient motion-induced phase effects.
      Images were acquired in phantoms and in healthy volunteers in brain, pelvic, and
      abdominal regions. RESULTS: Without navigator, diffusion-weighted IDEAL created
      artifacts in areas of motion. These were removed when the two-dimensional
      navigator was used to correct the phase, resulting in correct water-fat
      separation. CONCLUSION: DW-EPI with IDEAL and an integrated image navigator
      allows for robust water and fat separation in different body areas and are a time
      efficient alternative to standard fat-suppression techniques in DW-MRI.

PMID- 24723247
TI  - Promoting research resource identification at JCN.

PMID- 24723245
TI  - Curcumin inhibits TLR2/4-NF-kappaB signaling pathway and attenuates brain damage
      in permanent focal cerebral ischemia in rats.
AB  - Toll-like receptors 2 and 4 (TLR2/4) and the downstream nuclear factor-kappa B
      (NF-kappaB) signaling pathway, which mediate the inflammatory reaction in
      cerebral ischemia, were demonstrated to be involved in the extension of cerebral
      infarction and the aggravation of ischemic brain damage. Reports showed that
      curcumin provides neuroprotection against ischemic brain damage. In this study,
      we investigated whether curcumin inhibits the activation of TLR2/4-NF-kappaB
      signaling pathway in rats of permanent focal cerebral ischemia. Adult male
      Sprague-Dawley rats underwent permanent middle cerebral artery occlusion (pMCAO).
      Curcumin was administered by intraperitoneal injection twice at 2 and 12 h after
      the onset of ischemia. Neurological deficit scores, cerebral infarct size,
      morphological characteristic, and cerebral water content were measured after 24 h
      of pMCAO. The enzymatic activity of myeloperoxidase (MPO) was assessed after 24 h
      of pMCAO. Expression of TLR2 and TLR4 in ischemic brain was determined by western
      blot. Expression of NF-kappaB p65 in ischemic brain was detected by
      immunohistochemistry and western blot. The release of tumor necrosis factor-alpha
      (TNF-alpha) and interleukin-1beta (IL-1beta) in blood was examined by ELISA.
      Curcumin significantly reduced neurological deficit scores, cerebral infarct
      size, neuronal damage, cerebral water content, and MPO activity. It also
      inhibited the expression of TLR2/4 and decreased the expression and activity of
      NF-kappaB p65 in rat brain. In addition, curcumin attenuated the release of TNF
      alpha and IL-1beta in blood. Our results suggest that curcumin reduces
      inflammatory reaction and brain damage in a rat model of permanent focal cerebral
      ischemia. The neuroprotective effect and anti-inflammatory property of curcumin
      in cerebral ischemia might be associated with the inhibition of TLR2/4-NF-kappaB
      signaling pathway.

PMID- 24723242
TI  - What neuropsychology tells us about human tool use? The four constraints theory
      (4CT): mechanics, space, time, and effort.
AB  - Our understanding of human tool use comes mainly from neuropsychology,
      particularly from patients with apraxia or action disorganization syndrome.
      However, there is no integrative, theoretical framework explaining what these
      neuropsychological syndromes tell us about the cognitive/neural bases of human
      tool use. The goal of the present article is to fill this gap, by providing a
      theoretical framework for the study of human tool use: The Four Constraints
      Theory (4CT). This theory rests on two basic assumptions. First, everyday tool
      use activities can be formalized as multiple problem situations consisted of four
      distinct constraints (mechanics, space, time, and effort). Second, each of these
      constraints can be solved by the means of a specific process (technical
      reasoning, semantic reasoning, working memory, and simulation-based decision
      making, respectively). Besides presenting neuropsychological evidence for 4CT,
      this article shall address epistemological, theoretical and methodological issues
      I will attempt to resolve. This article will discuss how 4CT diverges from
      current cognitive models about several widespread hypotheses (e.g., notion of
      routine, direct and automatic activation of tool knowledge, simulation-based tool
      knowledge). 

PMID- 24723248
TI  - Laterally projecting cerebrospinal fluid-contacting cells in the lamprey spinal
      cord are of two distinct types.
AB  - Cerebrospinal fluid-contacting (CSF-c) cells are found in all vertebrates, but
      their function remains elusive. In the lamprey spinal cord, they surround the
      central canal and some have processes passing the gray matter to the lateral edge
      of the flattened spinal cord. Stimulation of CSF-c cells at the central canal
      elicits GABAergic inhibitory postsynaptic potentials (IPSPs) in intraspinal
      stretch receptor neurons (edge cells). Here, we characterize laterally projecting
      CSF-c cells according to their morphology, phenotype, and neuronal properties by
      using immunohistochemistry, retrograde tracing, calcium imaging, and whole-cell
      recordings. We identify two types of CSF-c cells. Type 1 cells have a bulb-like
      ending that protrudes into the central canal and a lateral process that ramifies
      ventrolaterally and laterally with a dense plexus surrounding the
      mechanosensitive dendrites of the edge cells. Most type 1 cells fire spontaneous
      action potentials that are abolished by tetrodotoxin, and all display spontaneous
      excitatory postsynaptic potentials and IPSPs that remain in the presence of
      tetrodotoxin. GABA and somatostatin are colocalized in type 1 cells, and they
      express both GABA and glutamate receptors. Type 2 cells, on the other hand, have
      a flat ending protruding into the central canal and a laterally projecting
      process that ramifies only at the lateral edge. These cells show immunoreactivity
      to taurine, but they do not express GABA or somatostatin, nor do they have any
      active neuronal properties. Type 2 cells might be a form of glia. Type 1 CSF-c
      cells are neurons and may play a modulatory role by influencing edge cells and
      thus the locomotor-related sensory feedback.

PMID- 24723249
TI  - Optimal vaccination policies for an SIR model with limited resources.
AB  - The purpose of the paper is to use analytical method and optimization tool to
      suggest a vaccination program intensity for a basic SIR epidemic model with
      limited resources for vaccination. We show that there are two different scenarios
      for optimal vaccination strategies, and obtain analytical solutions for the
      optimal control problem that minimizes the total cost of disease under the
      assumption of daily vaccine supply being limited. These solutions and their
      corresponding optimal control policies are derived explicitly in terms of initial
      conditions, model parameters and resources for vaccination. With sufficient
      resources, the optimal control strategy is the normal Bang-Bang control. However,
      with limited resources, the optimal control strategy requires to switch to time
      variant vaccination. 

PMID- 24723250
TI  - Sliding time of flight: sliding time of flight MR angiography using a dynamic
      image reconstruction method.
AB  - PURPOSE: To obtain three-dimensional (3D) MR angiography having high contrast
      between vessel and stationary background tissue, a novel technique called sliding
      time of flight (TOF) is proposed. METHODS: The proposed method relies on the
      property that flow-related enhancement (FRE) is maximized at the blood-entering
      slice in an imaging slab. For the proposed sliding TOF, a sliding stack-of-stars
      sampling and a dynamic MR image reconstruction algorithm were developed. To
      verify the performance of the proposed method, in vivo study was performed and
      the results were compared with multiple overlapping thin 3D slab acquisition
      (MOTSA) and sliding interleaved ky (SLINKY). RESULTS: In MOTSA and SLINKY, the
      variation of FRE resulted in severe venetian blind (MOTSA) or ghost (SLINKY)
      artifacts, while the vessel-contrast increased as the flip angle of
      radiofrequency (RF) pulses increased. On the other hand, the proposed method
      could provide high-contrast angiograms with reduced FRE-related artifacts.
      CONCLUSION: The sliding TOF can provide 3D angiography without image artifacts
      even if high flip angle RF pulses with thick slab excitation are used. Although
      remains of subsampling artifacts can be present in the reconstructed images, they
      can be reduced by MIP operation and resolved further by regularization
      techniques.

PMID- 24723251
TI  - Measurement of tumor blood flow in head and neck squamous cell carcinoma by
      pseudo-continuous arterial spin labeling: comparison with dynamic contrast
      enhanced MRI.
AB  - PURPOSE: To investigate the feasibility of tumor blood flow (TBF) measurement in
      head and neck squamous cell carcinoma (HNSCC) using pseudo-continuous arterial
      spin labeling (pCASL) in a comparison with dynamic contrast-enhanced (DCE)
      perfusion. MATERIALS AND METHODS: We prospectively scanned 18 patients with HNSCC
      using 3T magnetic resonance imaging (MRI) with both pCASL and DCE perfusion.
      Quantitative TBF value in the whole-tumor region of interest (ROI), and regional
      TBF in the ROIs of the central and peripheral areas in the tumor were
      respectively measured. Relative TBF value in the whole-tumor ROI was also
      calculated. We determined the correlation and agreement between each measured TBF
      by pCASL and DCE perfusion using Pearson's correlation coefficients, intraclass
      correlation coefficients (ICC), and Bland-Altman analysis. RESULTS: In the whole
      tumor ROIs, significant correlation was observed between the absolute TBF values
      (r = 0.72, P < 0.01), with an ICC of 0.72; moreover, higher correlation was
      observed in the relative TBF (r = 0.79). The correlation was higher in the
      peripheral ROI (r = 0.70) than the central ROI (r = 0.65), with an ICC of 0.62
      and 0.54, respectively. Bland-Altman plots revealed the underestimation of TBF by
      pCASL in central ROIs. CONCLUSION: TBF measurement by pCASL was feasible in
      patients with HNSCC.

PMID- 24723252
TI  - Depression in early adulthood: prevalence and psychosocial correlates among young
      Swiss men.
AB  - QUESTION UNDER STUDY: Depression in young adults is common, but data from
      Switzerland are scarce. Our study gives a point prevalence estimate of depression
      in young Swiss men, and describes the association between depression and
      education, material and social resources, and job/school satisfaction. METHODS:
      We used data from the cross-sectional Swiss Federal Surveys of Adolescents (ch-x)
      from 2010 to 2011 comprising 9,066 males aged between 18 and 25 years. Depression
      was assessed by means of self-reports using the Patient Health Questionnaire (PHQ
      9). Persons were categorised into three groups: depression, subthreshold
      depression, and no depression. We assessed the relationship between depression
      and education, material and social resources, and satisfaction with job/school.
      Differences according to depression status were tested with chi-square tests for
      categorical variables and one-way analyses of variance for continuous variables.
      RESULTS: Point prevalence of depression (3.60%) and subthreshold depression
      (3.62%) was high. Poor mental health was associated with lower education in young
      adults (p <0.001), and with their parents' education (p = 0.024). Social
      resources in persons with depression and subthreshold depression were
      substantially reduced (i.e., social support and satisfaction with social
      relations; both p <0.001). Young men with depression and subthreshold depression
      also reported a current lack of satisfaction with job/school (p <0.001).
      CONCLUSIONS: Prevalence of (subthreshold) depression is high in young Swiss men.
      Depression at this age might result in a bad long-term prognosis owing to its
      association with low satisfaction with job/school and low self-efficacy.
      Interventions should especially consider the lower social resources of young men
      with depression.

PMID- 24723253
TI  - Highly sensitive microfluidic competitive enzyme immunoassay based on
      chemiluminescence resonance energy transfer for the detection of neuron-specific
      enolase.
AB  - A microfluidic competitive enzyme immunoassay based on chemiluminescence
      resonance energy transfer (CRET) was developed for highly sensitive detection of
      neuron-specific enolase (NSE). The CRET system consisted of horseradish
      peroxidase (HRP)/luminol as a light donor and fluorescein isothiocyanate as an
      acceptor. When fluorescein isothiocyanate-labeled antibody binds with HRP-labeled
      antigen to form immunocomplex, the donor and acceptor are brought close each
      other and CRET occurs in the immunocomplex. In the MCE, the immunocomplex and
      excess HRP-NSE were separated, and the chemiluminescense intensity of
      immunocomplex was used to estimate NSE concentration. The calibration curve
      showed a linearity in the range of NSE concentrations from 9.0 to 950 pM with a
      correlation coefficient of 0.9964. Based on a S/N of 3, the detection limit for
      NSE determination was estimated to be 4.5 pM, which is two-order magnitude lower
      than that of without CRET detection. This assay was applied for NSE
      quantification in human serum. The obtained results demonstrated that the
      proposed immunoassay may serve as an alternative tool for clinical analysis of
      NSE.

PMID- 24723254
TI  - Operative modification for the prevention of device-related infection during
      NIPRO extracorporeal left ventricular assist device implantation.
AB  - An operative modification in which the NIPRO left ventricular assist device
      (LVAD) cannulas are passed through the intraperitoneal cavity is performed as the
      first-choice standard technique in our institution. Eighteen consecutive patients
      who underwent NIPRO LVAD implantation as heart transplantation candidates were
      enrolled in this study. The cannulas were passed through the intraperitoneal
      cavity in 11 patients (Group IP) and the extraperitoneal space in 7 patients
      (Group EP). A device-related major infection was defined as bloodstream infection
      and/or abscess formation in the deep tissue space. Device-related major infection
      occurred in 6 patients in Group IP and in 6 patients in Group EP. Of these
      patients, 3 patients in Group IP and 5 patients in Group EP suffered from
      uncontrollable bloodstream infection and finally died of development into
      multiple organ failure and/or cerebrovascular accidents. The actuarial rates of
      freedom from device-related major infection at 6 months after LVAD implantation
      were 100 % in Group IP and 38 % in Group EP, respectively (p = 0.02). Moreover,
      the actuarial survival rates after the initial device-related major infection in
      Group IP could be significantly higher than in Group EP (83 and 67 % at 6 months,
      p = 0.03). We demonstrated that this operative modification can contribute to
      prevention of progression of superficial skin infection to critical infection and
      to extension of the survival duration after the initial device-related major
      infection. 

PMID- 24723255
TI  - Probiotics for prevention of necrotizing enterocolitis in preterm infants.
AB  - BACKGROUND: Necrotizing enterocolitis (NEC) and nosocomial sepsis are associated
      with increased morbidity and mortality in preterm infants. Through prevention of
      bacterial migration across the mucosa, competitive exclusion of pathogenic
      bacteria, and enhancing the immune responses of the host, prophylactic enteral
      probiotics (live microbial supplements) may play a role in reducing NEC and the
      associated morbidity. OBJECTIVES: To compare the efficacy and safety of
      prophylactic enteral probiotics administration versus placebo or no treatment in
      the prevention of severe NEC or sepsis, or both, in preterm infants. SEARCH
      METHODS: For this update, searches were made of MEDLINE (1966 to October 2013),
      EMBASE (1980 to October 2013), the Cochrane Central Register of Controlled Trials
      (CENTRAL) in The Cochrane Library (2013, Issue 10), and abstracts of annual
      meetings of the Society for Pediatric Research (1995 to 2013). SELECTION
      CRITERIA: Only randomized or quasi-randomized controlled trials that enrolled
      preterm infants < 37 weeks gestational age or < 2500 g birth weight, or both,
      were considered. Trials were included if they involved enteral administration of
      any live microbial supplement (probiotics) and measured at least one prespecified
      clinical outcome. DATA COLLECTION AND ANALYSIS: Standard methods of The Cochrane
      Collaboration and its Neonatal Group were used to assess the methodologic quality
      of the trials and for data collection and analysis. MAIN RESULTS: Twenty-four
      eligible trials were included. Included trials were highly variable with regard
      to enrolment criteria (that is birth weight and gestational age), baseline risk
      of NEC in the control groups, timing, dose, formulation of the probiotics, and
      feeding regimens. In a meta-analysis of trial data, enteral probiotics
      supplementation significantly reduced the incidence of severe NEC (stage II or
      more) (typical relative risk (RR) 0.43, 95% confidence interval (CI) 0.33 to
      0.56; 20 studies, 5529 infants) and mortality (typical RR 0.65, 95% CI 0.52 to
      0.81; 17 studies, 5112 infants). There was no evidence of significant reduction
      of nosocomial sepsis (typical RR 0.91, 95% CI 0.80 to 1.03; 19 studies, 5338
      infants). The included trials reported no systemic infection with the
      supplemental probiotics organism. Probiotics preparations containing either
      lactobacillus alone or in combination with bifidobacterium were found to be
      effective. AUTHORS' CONCLUSIONS: Enteral supplementation of probiotics prevents
      severe NEC and all cause mortality in preterm infants. Our updated review of
      available evidence strongly supports a change in practice. Head to head
      comparative studies are required to assess the most effective preparations,
      timing, and length of therapy to be utilized.

PMID- 24723257
TI  - Dexamethasone altered steroidogenesis and changed redox status of granulosa
      cells.
AB  - Glucocorticoids have been widely used in clinical application for anti
      inflammatory and immunosuppressive function. Previous study reported that
      glucocorticoids adversely affect the reproductive system and can directly act on
      ovary. Here, we found that progesterone production induced by dexamethasone
      requiring activation of caspase-3 which may mediate differentiation and apoptosis
      of granulosa cells. Further study displayed that cellular glutathione level was
      increased and reactive oxygen species was decreased accompanied with unchanged
      mitochondrial membrane potential which may contribute to the maintenance of
      steroidogenesis in granulosa cells treated with dexamethasone. Dexamethasone also
      augmented the level of anti-Mullerian hormone secreted by preovulatory granulosa
      cells which indicated that dexamethasone may promote preantral follicles
      development. 

PMID- 24723258
TI  - Associations between rs965513/rs944289 and papillary thyroid carcinoma risk: a
      meta-analysis.
AB  - Single-nucleotide polymorphisms of rs965513 (9q22.33) and rs944289 (14q13.3) may
      be involved in the pathogenesis of papillary thyroid carcinoma (PTC). But,
      relevant genetic studies reported different results. The aim of this meta
      analysis was to derive a more precise assessment of the association of
      rs965513/rs944289 polymorphism with PTC risk. Relevant studies were identified
      using PubMed, ISI Web of knowledge, Medline, Embase, Google Scholar Search
      database, SinoMed (Chinese), CNKI (Chinese), GeNii (Japanese) and ICHUSHI
      (Japanese) (update to December, 2013). A total of eight case-control studies with
      52,363 subjects for rs965513 and 51,120 subjects for rs944289 were included. The
      results showed significant associations of rs965513/rs944289 with PTC risk
      existed in overall population (for rs965513, A vs. G: OR 1.71 (1.56-1.86); for
      rs944289, T vs. C: OR 1.29 (1.23-1.37)). Subgroup analysis by ethnicity showed
      that there were significant associations in Asians (for rs965513, A vs. G: OR
      1.48 (1.27-1.73); for rs944289, T vs. C: OR 1.35 (1.18-1.55)), in Europeans (for
      rs965513, A vs. G: OR 1.74 (1.61-1.88); for rs944289, T vs. C: OR 1.24 (1.14
      1.34)), and in Americans (for rs965513, A vs. G: OR 2.00 (1.76-2.27); for
      rs944289, T vs. C: OR 1.29 (1.14-1.47)). In conclusion, Rs965513 [A] and rs944289
      [T] are risk factors of PTC. Effect estimate for rs965513 polymorphism is higher
      in Americans than in Asians.

PMID- 24723256
TI  - Brain arteriovenous malformation modeling, pathogenesis, and novel therapeutic
      targets.
AB  - Patients harboring brain arteriovenous malformation (bAVM) are at life
      threatening risk of rupture and intracranial hemorrhage (ICH). The pathogenesis
      of bAVM has not been completely understood. Current treatment options are
      invasive, and ~ 20 % of patients are not offered interventional therapy because
      of excessive treatment risk. There are no specific medical therapies to treat
      bAVMs. The lack of validated animal models has been an obstacle for testing
      hypotheses of bAVM pathogenesis and testing new therapies. In this review, we
      summarize bAVM model development and bAVM pathogenesis and potential therapeutic
      targets that have been identified during model development. 

PMID- 24723259
TI  - Dioxin-induced fetal growth retardation: the role of a preceding attenuation in
      the circulating level of glucocorticoid.
AB  - Exposure of pregnant rats to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) at a low
      dose causes developmental disorders such as growth retardation and sexual
      immaturity in their pups. Our previous studies have demonstrated that TCDD
      attenuates the expression of pituitary luteinizing hormone in fetuses, resulting
      in the impairment of sexual behavior after they reach maturity. In this study, we
      focused on growth disturbance and investigated whether TCDD affects the
      expression of growth hormone (GH), another pituitary hormone which is essential
      for normal development in perinatal pups. The result showed that maternal
      exposure to TCDD (1 ug/kg) at gestational day (GD) 15 reduced the fetal
      expression of GH from the onset at GD18. In accordance with this, TCDD attenuated
      the pup weight during the perinatal period. We then examined the effect of TCDD
      on the serum concentration of corticosterone, which plays a key role in the
      proliferation of GH-producing cells, and found that TCDD reduces the circulating
      level of corticosterone in the mothers at GD18 and the male fetuses at GD19. The
      reduction in fetuses seems to be due to increased inactivation rather than
      reduced synthesis, because TCDD induces the fetal expression of hepatic enzymes
      participating in the metabolism of glucocorticoids without changing the
      expression of steroidogenic proteins in the pituitary-adrenal axis. Supplying
      corticosterone to TCDD-exposed mothers restored or tended to restore a TCDD
      induced reduction in pup weight as well as the levels of pituitary GH mRNA and
      serum GH. These results suggest that TCDD lowers GH expression and growth
      retardation owing, at least partially, to a reduction in the circulating level of
      glucocorticoid in pregnant mothers and their fetuses.

PMID- 24723260
TI  - Investigation of glucose intolerance in patients with normocalcemic primary
      hyperparathyroidism: 4-year follow-up.

PMID- 24723262
TI  - Update in nephrology: evidence published in 2013.

PMID- 24723261
TI  - Potentially inappropriate medication related to weakness in older acute medical
      patients.
AB  - BACKGROUND: The use of potentially inappropriate medications (PIMs) is common in
      the older population. Inappropriate medications as well as polypharmacy expose
      older people to a greater risk of adverse drug reactions and may result in
      hospitalizations. OBJECTIVE: To evaluate the prevalence of PIMs among acutely
      hospitalized patients aged >=65 years in an acute medical unit, and to
      investigate the relationship between use of PIMs and weakness. SETTING: This
      longitudinal observational study was undertaken in the Acute Medical Unit,
      Hvidovre Hospital, University of Copenhagen, Denmark. METHOD: Patients aged >=65
      years admitted to the acute medical unit during the period October to December
      2011 were included. Patients were interviewed at admission and at a follow-up
      visit 30 days after discharge. Data included information about medications,
      social status, functional status, cognitive status, handgrip strength, health
      related quality of life, visual acuity, days of hospitalization, and
      comorbidities, and was prospectively collected. Polypharmacy was defined as
      regular use of 5 or more drugs. The Charlson Comorbidity Index was used to
      categorize comorbidities. MAIN OUTCOME MEASURE: The prevalence of PIMs and the
      association with PIMs and functional status handgrip strength, HRQOL,
      comorbidities, social demographic data and vision. RESULTS: Seventy-one patients
      (55 % men) with a median age of 78.7 years participated. The median number of
      medications was eight per person. Eighty percent were exposed to polypharmacy.
      PIMs were used by 85 % of patients, and PIMs were associated with low functional
      status (p = 0.032), low handgrip strength (p = 0.006), and reduced health-related
      quality of life (p = 0.005), but not comorbidities (p = 0.63), age (p = 0.60),
      sex (p = 0.53), education (p = 0.94), cognition (p = 0.10), pain (p = 0.46), or
      visual acuity (p = 0.55). CONCLUSIONS: Use of PIMs was very common among older
      people admitted to an acute medical unit. The use of PIMs is associated with low
      functional status, low handgrip strength, and reduced health-related quality of
      life.

PMID- 24723263
TI  - Somatodendritic ion channel expression in substantia nigra pars compacta
      dopaminergic neurons across postnatal development.
AB  - Dopaminergic neurons of the substantia nigra pars compacta (SNc) are involved in
      the control of movement, sleep, reward, learning, and nervous system disorders
      and disease. To date, a thorough characterization of the ion channel phenotype of
      this important neuronal population is lacking. Using immunohistochemistry, we
      analyzed the somatodendritic expression of voltage-gated ion channel subunits
      that are involved in pacemaking activity in SNc dopaminergic neurons in 6-, 21-,
      and 40-day-old rats. Our results demonstrate that the same complement of
      somatodendritic ion channels is present in SNc dopaminergic neurons from P6 to
      P40. The major developmental changes were an increase in the dendritic range of
      the immunolabeling for the HCN, T-type calcium, Kv4.3, delayed rectifier, and SK
      channels. Our study sheds light on the ion channel subunits that contribute to
      the somatodendritic delayed rectifier (Kv1.3, Kv2.1, Kv3.2, Kv3.3), A-type
      (Kv4.3) and calcium-activated SK (SK1, SK2, SK3) potassium currents, IH (mainly
      HCN2, HCN4), and the L- (Cav1.2, Cav1.3) and T-type (mainly Cav3.1, Cav3.3)
      calcium currents in SNc dopaminergic neurons. Finally, no robust differences in
      voltage-gated ion channel immunolabeling were observed across the population of
      SNc dopaminergic neurons for each age examined, suggesting that differing levels
      of individual ion channels are unlikely to distinguish between specific
      subpopulations of SNc dopaminergic neurons. This is significant in light of
      previous studies suggesting that age- or region-associated variations in the
      expression profile of voltage-gated ion channels in SNc dopaminergic neurons may
      underlie their vulnerability to dysfunction and disease.

PMID- 24723264
TI  - Harnessing neurogenesis for the possible treatment of Parkinson's disease.
AB  - The discovery of neurogenesis in the adult brain has created new possibilities
      for therapeutics in neurodegenerative diseases. Neural precursor cells, which
      have been found in various parts of the brain, e.g., the subventricular zone
      (SVZ) and substantia nigra (SN), have promising potential to replace the
      extensive loss of neurons occurring in neurodegenerative disorders. In
      Parkinson's disease (PD) the degeneration of nigral dopaminergic neurons and
      consequently the nigrostriatal pathway, which has been found to innervate
      proximally to the SVZ, causes motor and cognitive impairments. There is strong
      evidence that neurogenesis is impaired in PD, which has been related to the
      nonmotor symptoms of the disease. Recent evidence supports that this impairment
      in neurogenesis is partially caused by the lack of dopamine in one of the adult
      neurogenic niches, the SVZ. Thus, restoring the dopaminergic pathway in PD
      patients may have implications not only for motor function improvement, but for
      other cognitive and autonomic symptoms. Currently, there are no effective
      treatments that can stop or reverse the neurodegeneration process in the brain.
      Here we review the neurogenic process and observed alterations found in PD animal
      models and postmortem brains of PD patients. Finally, we review several attempts
      to stimulate the neurogenic process for nigral and/or striatal dopaminergic
      restoration by transgenic expression, exercise, or cell therapy.

PMID- 24723268
TI  - Feasibility and outcomes regarding open and laparoscopic radical prostatectomy in
      patients with previous synthetic mesh inguinal hernia repair: meta-analysis and
      systematic review of 7,497 patients.
AB  - INTRODUCTION: The purpose of this article is to contribute information to the
      interpretation of the feasibility and outcomes regarding open, laparoscopic and
      robotic strategies of radical prostatectomy in patients with previous synthetic
      mesh inguinal hernia repair. MATERIALS AND METHODS: A bibliographic search
      covering the period from January 1980 to September 2012 was conducted in PubMed,
      MEDLINE and EMBASE. Database searches yielded 28 references. This analysis is
      based on the eleven studies that fulfilled the predefined criteria. RESULTS: A
      total of 7,497 patients were included. In the study group, there were 462
      patients. The surgical prostatectomy techniques were open in five studies,
      laparoscopic in three and robotic in the remaining three. The control group
      consisted in 7,035 patients. The comparison of the open procedure performed in
      patients with a previous mesh herniorrhaphy and controls shows that the number of
      lymph nodes removed resulted significantly lower and hospital stay with
      catheterization time results statistically longer. The comparison of the
      laparoscopic procedure does not evidence a statistically significant difference
      in terms of blood loss, operative time and catheterization time, while the
      comparison with the robotic group could not be performed for the lack of data.
      CONCLUSION: All patients need an adequate informed consent regarding the
      multitude of aspects which may be influenced by the mesh such as the possibility
      of hernia recurrence, mesh infection, need for mesh explantation, possibility of
      mesh erosion into the bowel or bladder, bladder neck contractures or
      postoperative urinary incontinence and a compromised nodal staging.

PMID- 24723269
TI  - The role of lymphadenectomy in the management of renal cell carcinoma.
AB  - The role of lymphadenectomy in the management of renal cell carcinoma has been
      established in staging but is less well defined as a therapeutic maneuver. Level
      one evidence suggests no survival benefit or increased complication rate with
      lymphadenectomy when performed concurrently with radical nephrectomy. However,
      several retrospective studies have identified a survival benefit when patients
      with increased risk of micrometastatic lymph node disease undergo
      lymphadenectomy. We perform a selective review of the literature and present the
      historical basis, risk assessment, use and development of nodal templates, and
      therapeutic benefits associated with the use of lymphadenectomy in the management
      of renal cell carcinoma.

PMID- 24723265
TI  - What's that gene (or protein)? Online resources for exploring functions of genes,
      transcripts, and proteins.
AB  - The genomic era has enabled research projects that use approaches including
      genome-scale screens, microarray analysis, next-generation sequencing, and mass
      spectrometry-based proteomics to discover genes and proteins involved in
      biological processes. Such methods generate data sets of gene, transcript, or
      protein hits that researchers wish to explore to understand their properties and
      functions and thus their possible roles in biological systems of interest. Recent
      years have seen a profusion of Internet-based resources to aid this process. This
      review takes the viewpoint of the curious biologist wishing to explore the
      properties of protein-coding genes and their products, identified using genome
      based technologies. Ten key questions are asked about each hit, addressing
      functions, phenotypes, expression, evolutionary conservation, disease
      association, protein structure, interactors, posttranslational modifications, and
      inhibitors. Answers are provided by presenting the latest publicly available
      resources, together with methods for hit-specific and data set-wide information
      retrieval, suited to any genome-based analytical technique and experimental
      species. The utility of these resources is demonstrated for 20 factors regulating
      cell proliferation. Results obtained using some of these are discussed in more
      depth using the p53 tumor suppressor as an example. This flexible and universally
      applicable approach for characterizing experimental hits helps researchers to
      maximize the potential of their projects for biological discovery. 

PMID- 24723270
TI  - Evaluation of fixation stability using different targets with the MP1
      microperimeter.
AB  - The aim of this study was to evaluate fixation stability using two different
      fixation targets with the Nidek MP1 microperimeter. Twenty-nine healthy subjects
      with a mean age of 26.53 +/- 7.35 years and visual acuity >=0.0 logMAR were
      enrolled in this study. Fifty-eight eyes of 29 patients without ophthalmic and/or
      systemic disease underwent a fixation test with the MP1 microperimeter. Fixation
      stability related to a red cross (central) and/or a red circle (pericentral)
      target was quantified using either Fujii classification or by calculating the
      bivariate contour ellipse area (BCEA). For statistical analysis, BCEA values were
      converted into their logarithms (logBCEA) and all data obtained were analyzed
      using paired Student's t test. The inclination values of the axis of BCEA were
      analyzed with Chi squared test. The mean values of logBCEA and the mean values of
      the major and minor axis of the ellipses related to the cross and the circle
      fixation target were significantly different (68.2 %, p = 0.00; 95.4 %, p = 0.00;
      99.6 %, p = 0.00, respectively) for each BCEA standard deviation. Fixation was
      significantly less stable for the pericentral fixation target in normal subjects,
      indicating an advantage for central fixation targets. These results are of
      particular interest when evaluation of changes in fixation is needed.

PMID- 24723271
TI  - Investigating the limitations of single breath-hold renal artery blood flow
      measurements using spiral phase contrast MR with R-R interval averaging.
AB  - PURPOSE: 1) To validate an R-R interval averaged golden angle spiral phase
      contrast magnetic resonance (RAGS PCMR) sequence against conventional cine PCMR
      for assessment of renal blood flow (RBF) in normal volunteers; and 2) To
      investigate the effects of motion and heart rate on the accuracy of flow
      measurements using an in silico simulation. MATERIALS AND METHODS: In 20 healthy
      volunteers RAGS (~6 sec breath-hold) and respiratory-navigated cine (~5 min) PCMR
      were performed in both renal arteries to assess RBF. A simulation of RAGS PCMR
      was used to assess the effect of heart rate (30-105 bpm), vessel expandability (0
      150%) and translational motion (x1.0-4.0) on the accuracy of RBF measurements.
      RESULTS: There was good agreement between RAGS and cine PCMR in the volunteer
      study (bias: 0.01 L/min, limits of agreement: -0.04 to +0.06 L/min, P = 0.0001).
      The simulation demonstrated a positive linear relationship between heart rate and
      error (r = 0.9894, P < 0.0001), a negative linear relationship between vessel
      expansion and error (r = -0.9484, P < 0.0001), and a nonlinear, heart rate
      dependent relationship between vessel translation and error. CONCLUSION: We have
      demonstrated that RAGS PCMR accurately measures RBF in vivo. However, the
      simulation reveals limitations in this technique at extreme heart rates (<40 bpm,
      >100 bpm), or when there is significant motion (vessel expandability: >80%,
      vessel translation: >x2.2).

PMID- 24723272
TI  - Fast low-specific absorption rate B0 -mapping along projections at high field
      using two-dimensional radiofrequency pulses.
AB  - PURPOSE: At 7 Tesla (T), conventional static field (B0 ) projection mapping
      techniques, e.g., FASTMAP, FASTESTMAP, lead to elevated specific absorption rates
      (SAR), requiring longer total acquisition times (TA). In this work, the series of
      adiabatic pulses needed for slab selection in FASTMAP is replaced by a single two
      dimensional radiofrequency (2D-RF) pulse to minimize TA while ensuring equal
      shimming performance. METHODS: Spiral gradients and 2D-RF pulses were designed to
      excite thin slabs in the small tip angle regime. The corresponding selection
      profile was characterized in phantoms and in vivo. After optimization of the
      shimming protocol, the spectral linewidths obtained after 2D localized shimming
      were compared with conventional techniques and published values from (Emir et al
      NMR Biomed 2012;25:152-160) in six different brain regions. RESULTS: Results on
      healthy volunteers show no significant difference (P > 0.5) between the
      spectroscopic linewidths obtained with the adiabatic (TA = 4 min) and the new low
      SAR and time-efficient FASTMAP sequence (TA = 42 s). The SAR can be reduced by
      three orders of magnitude and TA accelerated six times without impact on the
      shimming performances or quality of the resulting spectra. CONCLUSION:
      Multidimensional pulses can be used to minimize the RF energy and time spent for
      automated shimming using projection mapping at high field.

PMID- 24723273
TI  - Biological agents in monotherapy for the treatment of rheumatoid arthritis.
AB  - Rheumatoid arthritis (RA) is a chronic, systemic, inflammatory disease, which
      results in joint destruction and permanent disability. The advent of disease
      modifying antirheumatic drugs (DMARDs) has made a profound impact on the outcome
      and prognosis of RA. Methotrexate (MTX) is a central agent in RA therapy, and is
      used either alone or in combination with biological DMARDs. However, a large
      proportion of RA patients (20%-40%) either do not respond to or are unable to
      tolerate MTX or the alternative agents used in place of MTX (including
      leflunomide, sulfasalazine, azathioprine, hydroxycholoquine and combination
      DMARDs). For these patients, monotherapy with biological DMARDs is a key
      treatment option that balances tolerability with improved clinical outcomes. This
      article reviews the data for four biological agents approved for use as
      monotherapy in Switzerland (adalimumab, certolizumab pegol, etanercept and
      tocilizumab) in order to formulate a consensus statement on their roles in
      biologic monotherapy of RA. 

PMID- 24723276
TI  - Prevention of central line-associated bloodstream infections through quality
      improvement interventions: a systematic review and meta-analysis.
AB  - This systematic review and meta-analysis examines the impact of quality
      improvement interventions on central line-associated bloodstream infections in
      adult intensive care units. Studies were identified through Medline and manual
      searches (1995-June 2012). Random-effects meta-analysis obtained pooled odds
      ratios (ORs) and 95% confidence intervals (CIs). Meta-regression assessed the
      impact of bundle/checklist interventions and high baseline rates on intervention
      effect. Forty-one before-after studies identified an infection rate decrease (OR,
      0.39 [95% CI, .33-.46]; P < .001). This effect was more pronounced for trials
      implementing a bundle or checklist approach (P = .03). Furthermore, meta-analysis
      of 6 interrupted time series studies revealed an infection rate reduction 3
      months postintervention (OR, 0.30 [95% CI, .10-.88]; P = .03). There was no
      difference in infection rates between studies with low or high baseline rates (P
      = .18). These results suggest that quality improvement interventions contribute
      to the prevention of central line-associated bloodstream infections.
      Implementation of care bundles and checklists appears to yield stronger risk
      reductions. 

PMID- 24723277
TI  - Prosthetic joint replacement: should orthopedists check urine because it's there?

PMID- 24723278
TI  - Middle East respiratory syndrome coronavirus: a case-control study of
      hospitalized patients.
AB  - BACKGROUND: There is a paucity of data regarding the differentiating
      characteristics of patients with laboratory-confirmed and those negative for
      Middle East respiratory syndrome coronavirus (MERS-CoV). METHODS: This is a
      hospital-based case-control study comparing MERS-CoV-positive patients (cases)
      with MERS-CoV-negative controls. RESULTS: A total of 17 case patients and 82
      controls with a mean age of 60.7 years and 57 years, respectively (P = .553),
      were included. No statistical differences were observed in relation to sex, the
      presence of a fever or cough, and the presence of a single or multilobar
      infiltrate on chest radiography. The case patients were more likely to be
      overweight than the control group (mean body mass index, 32 vs 27.8; P = .035),
      to have diabetes mellitus (87% vs 47%; odds ratio [OR], 7.24; P = .015), and to
      have end-stage renal disease (33% vs 7%; OR, 7; P = .012). At the time of
      admission, tachypnea (27% vs 60%; OR, 0.24; P = .031) and respiratory distress
      (15% vs 51%; OR, 0.15; P = .012) were less frequent among case patients. MERS-CoV
      patients were more likely to have a normal white blood cell count than the
      control group (82% vs 52%; OR, 4.33; P = .029). Admission chest radiography with
      interstitial infiltrates was more frequent in case patients than in controls (67%
      vs 20%; OR, 8.13; P = .001). Case patients were more likely to be admitted to the
      intensive care unit (53% vs 20%; OR, 4.65; P = .025) and to have a high mortality
      rate (76% vs 15%; OR, 18.96; P < .001). CONCLUSIONS: Few clinical predictors
      could enhance the ability to predict which patients with pneumonia would have
      MERS-CoV. However, further prospective analysis and matched case-control studies
      may shed light on other predictors of infection.

PMID- 24723279
TI  - Multidrug-resistant tuberculosis with fluoroquinolone resistance: sinister
      association with other drugs and ominous implications for treatment.

PMID- 24723280
TI  - Is asymptomatic bacteriuria a risk factor for prosthetic joint infection?
AB  - BACKGROUND: Infection is a major complication after total joint arthroplasty. The
      urinary tract is a possible source of surgical site contamination, but the role
      of asymptomatic bacteriuria (ASB) before elective surgery and the subsequent risk
      of infection is poorly understood. METHODS: Candidates for total hip or total
      knee arthroplasty were reviewed in a multicenter cohort study. A urine sample was
      cultured in all patients, and those with ASB were identified. Preoperative
      antibiotic treatment was decided on an individual basis, and it was not mandatory
      or randomized. The primary outcome was prosthetic joint infection (PJI) in the
      first postoperative year. RESULTS: A total of 2497 patients were enrolled. The
      prevalence of ASB was 12.1% (303 of 2497), 16.3% in women and 5.0% in men (odds
      ratio, 3.67; 95% confidence interval, 2.65-5.09; P < .001). The overall PJI rate
      was 1.7%. The infection rate was significantly higher in the ASB group than in
      the non-ASB group (4.3% vs 1.4%; odds ratio, 3.23; 95% confidence interval, 1.67
      6.27; P = .001). In the ASB group, there was no significant difference in PJI
      rate between treated (3.9%) and untreated (4.7%) patients. The ASB group had a
      significantly higher proportion of PJI due to gram-negative microorganisms than
      the non-ASB group, but these did not correlate to isolates from urine cultures.
      CONCLUSIONS: ASB was an independent risk factor for PJI, particularly that due to
      gram-negative microorganisms. Preoperative antibiotic treatment did not show any
      benefit and cannot be recommended.

PMID- 24723281
TI  - Dolutegravir: a next-generation integrase inhibitor for treatment of HIV
      infection.
AB  - Dolutegravir (DTG), a next-generation integrase strand transfer inhibitor
      (INSTI), was recently approved for use in the treatment of human immunodeficiency
      virus infection. In treatment-naive trial participants, DTG given at 50 mg once
      daily without pharmacologic boosting combined with a standard nucleoside backbone
      was shown to be noninferior or superior to first-line regimens containing
      efavirenz, darunavir/ritonavir, or raltegravir regardless of pretreatment viral
      load. This drug also exhibited efficacy in antiretroviral therapy-experienced
      participants and has proven to retain activity when dosed twice daily in some
      participants harboring resistance to the other INSTIs, raltegravir and
      elvitegravir. DTG has few drug interactions and is taken without regard to meals.
      It causes benign elevations in serum creatinine based on its inhibition of
      tubular creatinine secretion without affecting the glomerular filtration rate.
      Overall, DTG is well tolerated, with headache and insomnia being the most
      frequently reported adverse events. 

PMID- 24723282
TI  - A phase 3 randomized double-blind comparison of ceftobiprole medocaril versus
      ceftazidime plus linezolid for the treatment of hospital-acquired pneumonia.
AB  - BACKGROUND: Ceftobiprole, the active moiety of ceftobiprole medocaril, is a novel
      broad-spectrum cephalosporin, with bactericidal activity against a wide range of
      gram-positive bacteria, including Staphylococcus aureus (including methicillin
      resistant strains) and penicillin- and ceftriaxone-resistant pneumococci, and
      gram-negative bacteria, including Enterobacteriaceae and Pseudomonas aeruginosa.
      METHODS: This was a double-blind, randomized, multicenter study of 781 patients
      with hospital-acquired pneumonia (HAP), including 210 with ventilator-associated
      pneumonia (VAP). Treatment was intravenous ceftobiprole 500 mg every 8 hours, or
      ceftazidime 2 g every 8 hours plus linezolid 600 mg every 12 hours; primary
      outcome was clinical cure at the test-of-cure visit. RESULTS: Overall cure rates
      for ceftobiprole vs ceftazidime/linezolid were 49.9% vs 52.8% (intent-to-treat
      [ITT], 95% confidence interval [CI] for the difference, -10.0 to 4.1) and 69.3%
      vs 71.3% (clinically evaluable [CE], 95% CI, -10.0 to 6.1). Cure rates in HAP
      (excluding VAP) patients were 59.6% vs 58.8% (ITT, 95% CI, -7.3 to 8.8), and
      77.8% vs 76.2% (CE, 95% CI, -6.9 to 10.0). Cure rates in VAP patients were 23.1%
      vs 36.8% (ITT, 95% CI, -26.0 to -1.5) and 37.7% vs 55.9% (CE, 95% CI, -36.4 to
      0). Microbiological eradication rates in HAP (excluding VAP) patients were,
      respectively, 62.9% vs 67.5% (microbiologically evaluable [ME], 95% CI, -16.7 to
      7.6), and in VAP patients 30.4% vs 50.0% (ME, 95% CI, -38.8 to -0.4). Treatment
      related adverse events were comparable for ceftobiprole (24.9%) and
      ceftazidime/linezolid (25.4%). CONCLUSIONS: Ceftobiprole is a safe and effective
      bactericidal antibiotic for the empiric treatment of HAP (excluding VAP). Further
      investigations are needed before recommending the use of ceftobiprole in VAP
      patients. Clinical Trials Registration. NCT00210964, NCT00229008.

PMID- 24723283
TI  - Improved virologic suppression with HIV subspecialty care in a large prison
      system using telemedicine: an observational study with historical controls.
AB  - Correctional populations have an elevated human immunodeficiency virus (HIV)
      prevalence, yet many individuals lack access to subspecialty care. Our study
      showed that HIV-infected inmates had significantly greater virologic suppression
      and higher CD4 T-lymphocyte counts when managed by a multidisciplinary team of
      subspecialists conducting clinics via telemedicine. In other studies, these
      outcomes have been associated with reductions on HIV-related morbidity and
      mortality, as well as HIV transmission. 

PMID- 24723285
TI  - Should the indication of pneumococcal polysaccharide vaccine in children be
      definitively withdrawn?

PMID- 24723284
TI  - Immunogenicity and safety of the quadrivalent human papillomavirus vaccine in HIV
      1-infected women.
AB  - BACKGROUND: Women infected with human immunodeficiency virus (HIV) are
      disproportionately affected by human papillomavirus (HPV)-related anogenital
      disease, particularly with increased immunosuppression. AIDS Clinical Trials
      Group protocol A5240 was a trial of 319 HIV-infected women in the United States,
      Brazil, and South Africa to determine immunogenicity and safety of the
      quadrivalent HPV vaccine in 3 strata based on screening CD4 count: >350 (stratum
      A), 201-350 (stratum B), and <=200 cells/uL (stratum C). METHODS: Safety and
      serostatus of HPV types 6, 11, 16, and 18 were examined. HPV serological testing
      was performed using competitive Luminex immunoassay (HPV-4 cLIA). HPV type
      specific seroconversion analysis was done for participants who were seronegative
      for the given type at baseline. RESULTS: Median age of patients was 36 years; 11%
      were white, 56% black, and 31% Hispanic. Median CD4 count was 310 cells/uL, and
      40% had undetectable HIV-1 load. No safety issues were identified. Seroconversion
      proportions among women at week 28 for HPV types 6, 11,16, and 18 were 96%, 98%,
      99%, and 91%, respectively, for stratum A; 100%, 98%, 98%, and 85%, respectively,
      for stratum B, and 84%, 92%, 93%, and 75%, respectively, for stratum C.
      CONCLUSIONS: The quadrivalent HPV vaccine targeted at types 6, 11, 16, and 18 was
      safe and immunogenic in HIV-infected women aged 13-45 years. Women with HIV RNA
      load >10 000 copies/mL and/or CD4 count <200 cells/uL had lower rates of
      seroconversion rates. Clinical Trials Registration. NCT00604175.

PMID- 24723286
TI  - Heterosexual risk of HIV transmission per sexual act under combined
      antiretroviral therapy: systematic review and bayesian modeling.
AB  - BACKGROUND: Although essential for patient counseling and quality of life of
      human immunodeficiency virus (HIV)-infected individuals, the risk of HIV
      transmission during 1 unprotected sex act with an HIV-infected person under
      combination antiretroviral therapy (cART) remains unknown. METHODS: We reviewed
      systematically the literature for studies on HIV transmission among heterosexual
      HIV-serodiscordant couples, where the infected partner was on cART, with regular
      virological monitoring, reporting on condom use and sexual activity. We used
      Bayesian statistics to combine data from selected studies, to investigate the per
      act risk of HIV transmission through unprotected sex with an HIV-infected person
      on cART for >6 months. RESULTS: At most, 1 HIV transmission, over an estimated
      113 480 sex acts, of which 17% were not condom protected, was reported within
      1672 HIV-serodiscordant couples where the index partner had been treated for >6
      months. Data were insufficient to determine whether the reported transmission
      occurred before or after 6 months of cART. We estimated the upper-bound per-act
      risk of HIV transmission at either 8.7 or 13:100 000, depending on whether the
      transmission occurred before or after 6 months of cART. These estimates applied
      whether or not index partners were virally suppressed. Estimating an upper-bound
      risk <1:100 000 would require observing no HIV transmission while collecting >12
      times the available amount of data. CONCLUSIONS: Available data do not support
      zero risk of HIV transmission under cART. The per-act risk of HIV transmission
      through unprotected sex with HIV-infected individuals on cART in comprehensive
      care for >6 months (whether or not virally suppressed) is <13:100 000. Estimating
      a 10-fold lower upper-bound risk may be unfeasible due to high condom use among
      HIV-serodiscordant couples in most research studies.

PMID- 24723288
TI  - Patient attrition between the emergency department and clinic among individuals
      presenting for HIV nonoccupational postexposure prophylaxis.
AB  - BACKGROUND: Nonoccupational postexposure prophylaxis (nPEP) is recommended after
      a sexual or parenteral exposure to human immunodeficiency virus (HIV). Patients
      frequently seek care in an emergency department (ED) after an exposure and are
      usually referred to an HIV clinic for further management. There have been few
      data on determinants of attrition after presentation to EDs for nPEP. METHODS:
      From July 2010 to June 2011, we prospectively recorded all referrals to nPEP
      programs from 2 large EDs at 2 academic medical centers in Boston, Massachusetts.
      Data were recorded on patient demographics, nature of potential HIV exposures,
      referrals to and attendance at HIV clinics, and reported completion of 28 days of
      antiretroviral therapy (ART). Multivariable logistic regression was used to
      evaluate risk factors for (1) patient attrition between the ED and HIV clinic
      follow-up and (2) documented completion of ART. RESULTS: Of 180 individuals who
      were referred to clinic follow-up for nPEP care from the ED, 98 (54.4%) attended
      a first nPEP clinic visit and 43 (23.9%) had documented completion of a 28-day
      course of ART. Multivariable analysis revealed older age (adjusted odds ratio
      [aOR], 0.96; 95% confidence interval [CI], .93-.99) and self-payment (aOR, 0.32;
      95% CI, .11-.97) were significant predictors for failing to attend an initial HIV
      clinic appointment. Women were less likely than men to complete a 28-day ART
      regimen (aOR, 0.34; 95% CI, .15-.79). CONCLUSIONS: Commonly used nPEP delivery
      models may not be effective for all patients who present with nonoccupational
      exposures to HIV. Interventions are needed to improve rates of follow-up and
      completion of nPEP to reduce the risk of preventable HIV infections.

PMID- 24723289
TI  - Electrochemical adsorption of OH on Pt(111) in alkaline solutions: combining DFT
      and molecular dynamics.
AB  - The adsorption of OH on Pt(111) in alkaline solution has been investigated by a
      method that combines density functional theory, molecular dynamics, and quantum
      statistical mechanics. In particular, we have calculated the free energy surface
      for the reaction. A physisorbed hydroxide ion in a metastable state and a stable
      adsorbed uncharged OH group are observed. The energy of activation at equilibrium
      is comparatively low, so that the reaction is fast. 

PMID- 24723287
TI  - The HIV, syphilis, and HCV epidemics among female sex workers in china: results
      from a serial cross-sectional study between 2008 and 2012.
AB  - BACKGROUND: Studies on the transmission of human immunodeficiency virus (HIV) and
      sexually transmitted diseases in female sex workers (FSWs) have been limited
      primarily to inferences drawn by focusing on defined geographical areas. METHODS
      AND FINDINGS: This serial cross-sectional study was conducted in mainland China
      from 2008 through 2012. Data for 827 079 participants was analyzed. We classified
      venues such as karaoke bars and hotels as high tier and venues such as hair
      salons and barbershops, massage parlors, and other public outdoor venues as low
      tier based on the participants' socioeconomic status. FSWs who worked at the
      venues and those who were present on the days of the survey were recruited. The
      prevalence of HIV decreased from 0.6% in 2008 to 0.3% in 2012, the syphilis
      prevalence ranged from 2.4% to 3.2% between 2008 and 2012, and hepatitis C virus
      (HCV) prevalence decreased from 0.9% in 2008 to 0.8% in 2012. Further, we found
      that HIV, syphilis, and HCV prevalence proportions were high in FSWs from low
      tiers. CONCLUSIONS: HIV, syphilis, and HCV prevalence among FSWs in our study
      decreased during the study period. Comprehensive intervention strategies,
      particularly those that focus on low-tier and older FSWs, are needed in order to
      decrease the disease burden in this population.

PMID- 24723290
TI  - Mycosubtilin and surfactin are efficient, low ecotoxicity molecules for the
      biocontrol of lettuce downy mildew.
AB  - The use of surfactin and mycosubtilin as an eco-friendly alternative to control
      lettuce downy mildew caused by the obligate pathogen Bremia lactucae was
      investigated. Preliminary ecotoxicity evaluations obtained from three different
      tests revealed the rather low toxicity of these lipopeptides separately or in
      combination. The EC50 (concentration estimated to cause a 50 % response by the
      exposed test organisms) was about 100 mg L(-1) in Microtox assays and 6 mg L(-1)
      in Daphnia magna immobilization tests for mycosubtilin and 125 mg L(-1) and 25 mg
      L(-1) for surfactin, respectively. The toxicity of the mixture
      mycosubtilin/surfactin (1:1, w/w) was close to that obtained with mycosubtilin
      alone. In addition, the very low phytotoxic effect of these lipopeptides has been
      observed on germination and root growth of garden cress Lepidium sativum L. While
      a surfactin treatment did not influence the development of B. lactucae on lettuce
      plantlets, treatment with 100 mg L(-1) of mycosubtilin produced about seven times
      more healthy plantlets than the control samples, indicating that mycosubtilin
      strongly reduced the development of B. lactucae. The mixture
      mycosubtilin/surfactin (50:50 mg L(-1)) gave the same result on B. lactucae
      development as 100 mg L(-1) of mycosubtilin. The results of ecotoxicity as well
      as those obtained in biocontrol experiments indicated that the presence of
      surfactin enhances the biological activities of mycosubtilin. Mycosubtilin and
      surfactin were thus found to be efficient compounds against lettuce downy mildew,
      with low toxicity compared to the toxicity values of chemical pesticides. This is
      the first time that Bacillus lipopeptides have been tested in vivo against an
      obligate pathogen and that ecotoxic values have been given for surfactin and
      mycosubtilin.

PMID- 24723291
TI  - Heavy metal-induced glutathione accumulation and its role in heavy metal
      detoxification in Phanerochaete chrysosporium.
AB  - Phanerochaete chrysosporium are known to be vital hyperaccumulation species for
      heavy metal removal with admirable intracellular bioaccumulation capacity. This
      study analyzes the heavy metal-induced glutathione (GSH) accumulation and the
      regulation at the intracellular heavy metal level in P. chrysosporium. P.
      chrysosporium accumulated high levels of GSH, accompanied with high intracellular
      concentrations of Pb and Cd. Pb bioaccumulation lead to a narrow range of
      fluctuation in GSH accumulation (0.72-0.84 MUmol), while GSH plummeted under Cd
      exposure at the maximum value of 0.37 MUmol. Good correlations between time
      course GSH depletion and Cd bioaccumulation were determined (R (2) > 0.87), while
      no significant correlations have been found between GSH variation and Pb
      bioaccumulation (R (2) < 0.38). Significantly, concentration-dependent molar
      ratios of Pb/GSH ranging from 0.10 to 0.18 were observed, while molar ratios of
      Cd/GSH were at the scope of 1.53-3.32, confirming the dominant role of GSH in Cd
      chelation. The study also demonstrated that P. chrysosporium showed considerable
      hypertolerance to Pb ions, accompanied with demand-driven stimulation in GSH
      synthesis and unconspicuous generation of reactive oxygen stress. GSH plummeted
      dramatically response to Cd exposure, due to the strong affinity of GSH to Cd and
      the involvement of GSH in Cd detoxification mechanism mainly as Cd chelators.
      Investigations into GSH metabolism and its role in ameliorating metal toxicity
      can offer important information on the application of the microorganism for
      wastewater treatment.

PMID- 24723292
TI  - Identification of a novel carotenoid, 2'-isopentenylsaproxanthin, by Jejuia
      pallidilutea strain 11shimoA1 and its increased production under alkaline
      condition.
AB  - Carotenoids are a class of naturally occurring pigment, carrying out important
      biological functions in photosynthesis and involved in environmental responses
      including nutrition in organisms. Saproxanthin and myxol, which have monocyclic
      carotenoids with a gamma-carotene skeleton, have been reported to show a stronger
      antioxidant activity than those with beta-carotene and zeaxanthin. In this
      research, a yellow-orange bacterium of strain 11shimoA1 (JCM19538) was isolated
      from a seaweed collected at Nabeta Bay (Shizuoka, Japan). The 16S rRNA gene
      sequence of strain 11shimoA1 revealed more than 99.99 % similarity with those of
      Jejuia pallidilutea strains in the family Flavobacteriaceae. Strain 11shimoA1
      synthesized two types of carotenoids. One of them was (3R, 3'R)-zeaxanthin with
      dicyclic structure and another was identified as (3R, 2'S)-2'
      isopentenylsaproxanthin, a novel monocyclic carotenoid with pentenyl residue at C
      2' position of saproxanthin, using FAB-MS, (1)H NMR, and CD analyses. Culturing
      strain 11shimoA1 in an alkaline medium at pH 9.2 resulted in a markedly increased
      in production of 2'-isopentenylsaproxanthin per dry cell weight, but a decreased
      in zeaxanthin production as compared to their respective production levels in
      medium with pH 7.0. These carotenoids are likely to play some roles in the
      adaptation of the bacterium to the environmental conditions.

PMID- 24723293
TI  - Complex regulation of hydrolytic enzyme genes for cellulosic biomass degradation
      in filamentous fungi.
AB  - Filamentous fungi produce cellulolytic and hemicellulolytic enzymes in response
      to small inducer molecules liberated from cellulosic biomass. Enzyme production
      is mainly regulated at the level of transcription. The first transcription factor
      identified as being involved in cellulosic biomass degradation was XlnR, which
      mediates D-xylose-triggered induction of xylanolytic and cellulolytic genes in
      Aspergillus. XlnR has played the leading role for over a decade in studies aimed
      at clarification of gene regulation related to cellulosic biomass degradation.
      Very recently, several new transcription factors were identified, namely Clr-1/2
      in Neurospora; ManR, McmA, and ClbR in Aspergillus; and BglR in Trichoderma, all
      of which participate in the regulation of cellulolytic and/or hemicellulolytic
      enzyme production. Furthermore, as well as the carbon sources available, other
      factors such as light signaling and anti-sense RNA accumulation have been shown
      to contribute to this regulation. Here, we review the recent advancements
      demonstrating that multiple factors coordinately regulate the expression of
      cellulosic biomass degrading enzyme genes. 

PMID- 24723294
TI  - Purification of an amide hydrolase DamH from Delftia sp. T3-6 and its gene
      cloning, expression, and biochemical characterization.
AB  - A highly active amide hydrolase (DamH) was purified from Delftia sp. T3-6 using
      ammonium sulfate precipitation, diethylaminoethyl anion exchange, hydrophobic
      interaction chromatography, and Sephadex G-200 gel filtration. The molecular mass
      of the purified enzyme was estimated to be 32 kDa by sodium dodecyl sulfate (SDS)
      polyacrylamide gel electrophoresis. The sequence of the N-terminal 15 amino acid
      residues was determined to be Gly-Thr-Ser-Pro-Gln-Ser-Asp-Phe-Leu-Arg-Ala-Leu-Phe
      Gln-Ser. Based on the N-terminal sequence and results of peptide mass
      fingerprints, the gene (damH) was cloned by PCR amplification and expressed in
      Escherichia coli BL21(DE3). DamH was a bifunctional hydrolase showing activity to
      amide and ester bonds. The specific activities of recombinant DamH were 5,036
      U/mg for 2'-methyl-6'-ethyl-2- chloroacetanilide (CMEPA) (amide hydrolase
      function) and 612 U/mg for 4-nitrophenyl acetate (esterase function). The optimum
      substrate of DamH was CMEPA, with K m and k cat values of 0.197 mM and 2,804.32
      s(-1), respectively. DamH could also hydrolyze esters such as 4-nitrophenyl
      acetate, glycerol tributyrate, and caprolactone. The optimal pH and temperature
      for recombinant DamH were 6.5 and 35  degrees C, respectively; the enzyme was
      activated by Mn(2+) and inhibited by Cu(2+), Zn(2+), Ni(2+), and Fe(2+). DamH was
      inhibited strongly by phenylmethylsulfonyl and SDS and weakly by
      ethylenediaminetetraacetic acid and dimethyl sulfoxide.

PMID- 24723296
TI  - Evaluation of inhibitory effects of heavy metals on anaerobic ammonium oxidation
      (anammox) by continuous feeding tests.
AB  - To facilitate the application of anaerobic ammonium oxidation (anammox) to a
      nitrogen removal process, the effects of heavy metals (Ni, Cu, Co, Zn, and Mo) on
      anammox bacteria entrapped in gel carriers were examined by conducting continuous
      feeding tests for each metal. The results show that all anammox activities
      decreased by more than 10 % when influent concentrations of Ni, Cu, Co, Zn, and
      Mo were 5, 5, 5, 10, and 0.2 mg/L, respectively. It was observed that the effects
      of Ni, Cu, Co, and Zn on anammox activity were reversible and that of Mo on
      anammox activity was irreversible. Anammox activity was not affected when
      influent containing mixed Ni, Cu, Co, and Zn (0.5 mg/L) was fed into the reactor.

PMID- 24723295
TI  - Inhibition of Candida albicans virulence factors by novel levofloxacin
      derivatives.
AB  - Candida albicans is an important opportunistic fungal pathogen, responsible for
      biofilm associated infections in immunocompromised patients. The aim of the
      present study was to investigate the antibiofilm properties of novel levofloxacin
      derivatives on C. albicans biofilms. The levofloxacin derivatives at their
      Biofilm Inhibitory Concentrations (BIC) were able to inhibit the biofilms of C.
      albicans, the yeast-to-hyphal transition and were also able to disrupt their
      mature biofilms. Furthermore, Real-time PCR analysis showed that the expression
      of ergosterol biosynthesis pathway gene (ERG11) and the efflux pump-encoding
      genes (CDR1 and MDR1) was decreased upon treatment with the levofloxacin
      derivatives. The total ergosterol content quantified using UV spectrophotomer
      showed decrease in ergosterol in the presence of levofloxacin derivatives.
      Overall, levofloxacin derivatives (6a, 6c and 7d) are capable of inhibiting C.
      albicans virulence factors. Therefore, these compounds with potential therapeutic
      implications can be used as new strategy to treat biofilm-related candidal
      infections.

PMID- 24723297
TI  - Traveling wave electroosmosis: the influence of electrode array geometry.
AB  - We used a mathematical model describing traveling-wave electroosmotic micropumps
      to explain their rather poor ability to work against pressure loads. The
      mathematical model is based upon the Poisson-Nernst-Planck-Navier-Stokes
      approach, that is, a direct numerical simulation, which allows a detail study of
      the energy transformations and the charging dynamics of the electric double
      layers. Using Matlab and COMSOL Multiphysics, we performed a set of extensive
      parametric studies to determine the dependence of generated electroosmotic flow
      on the geometric arrangement of the pump. The results suggest that the
      performance of AC electroosmotic pumps should improve with miniaturization. The
      AC electroosmosis is likely to be suitable only at submicrometer scale, as the
      pump's ability to work against pressure load diminishes rapidly when increasing
      the channel diameter.

PMID- 24723298
TI  - Ionic liquids as stationary phases in gas chromatography: determination of
      chlorobenzenes in soils.
AB  - The present research focuses on the evaluation of different ionic liquid (IL)
      stationary phases in gas chromatography. The different IL columns were evaluated
      in terms of peak resolution (Rs) and peak symmetry for the separation of the
      chlorobenzenes. The determination of chlorobenzenes in soil samples by means of
      the optimal IL stationary phase (SLB-IL82) is proposed as an application. Soil
      pretreatment was based on a simplified quick, easy, cheap, effective, rugged, and
      safe extraction procedure and a large injection volume via a programed
      temperature vaporizer working in solvent vent mode. The retention time of the
      chlorobenzenes increased as the polarity of the IL column decreased. SLB-IL82 is
      the stationary phase that provides the best values as regards Rs and asymmetry
      factor. Soil sample blanks were spiked with the analytes before subjecting the
      sample to the extraction process. The existence of a matrix effect was checked
      and the analytical characteristics of the method were determined in a fortified
      garden soil sample. The method provided good linearity, good repeatability and
      reproducibility values, and the LODs were in the 0.1-4.7 MUg/kg range. Two
      fortified soil samples were applied to validate the proposed methodology.

PMID- 24723299
TI  - MRI-based computational fluid dynamics for diagnosis and treatment prediction:
      clinical validation study in patients with coarctation of aorta.
AB  - PURPOSE: To reduce the need for diagnostic catheterization and optimize treatment
      in a variety of congenital heart diseases, magnetic resonance imaging (MRI)-based
      computational fluid dynamics (CFD) is proposed. However, data about the accuracy
      of CFD in a clinical context are still sparse. To fill this gap, this study
      compares MRI-based CFD to catheterization in the coarctation of aorta (CoA)
      setting. MATERIALS AND METHODS: Thirteen patients with CoA were investigated by
      routine MRI prior to catheterization. 3D whole-heart MRI was used to reconstruct
      geometries and 4D flow-sensitive phase-contrast MRI was used to acquire flows.
      Peak systolic flows were simulated using the program FLUENT. RESULTS: Peak
      systolic pressure drops in CoA measured by catheterization and CFD correlated
      significantly for both pre- and posttreatment measurements (pre: r = 0.98, p =
      0.00; post: r = 0.87, p = 0.00). The pretreatment bias was -0.5 +/- 3.33 mmHg
      (95% confidence interval -2.55 to 1.47 mmHg). CFD predicted a reduction of the
      peak systolic pressure drop after treatment that ranged from 17.6 +/- 5.56 mmHg
      to 6.7 +/- 5.58 mmHg. The posttreatment bias was 3.0 +/- 2.91 mmHg (95% CI -1.74
      to 5.43 mmHg). CONCLUSION: Peak systolic pressure drops can be reliably
      calculated using MRI-based CFD in a clinical setting. Therefore, CFD might be an
      attractive noninvasive alternative to diagnostic catheterization.

PMID- 24723300
TI  - Intracellular Zn(2+) signaling in cognition.
AB  - Brain zinc homeostasis is strictly controlled under healthy conditions,
      indicating the importance of zinc for physiological function in the brain. A part
      of zinc in the brain exists in the synaptic vesicles, is released from a subclass
      of glutamatergic neurons (i.e., zincergic neurons), and serves as a signal factor
      (Zn(2+) signal) in the intracellular (cytosol) compartment as well as in the
      extracellular compartment. Zn(2+) signaling is dynamically linked to glutamate
      signaling and may be involved in synaptic plasticity, such as long-term
      potentiaion and cognitive activity. In zincergic synapses, intracellular Zn(2+)
      signaling in the postsynaptic neurons, which is linked to Zn(2+) release from
      zincergic neuron terminals, plays a role in cognitive activity. When nonzincergic
      synapses participate in cognition, on the other hand, it is possible that
      intracellular Zn(2+) signaling, which is due mainly to Zn(2+) release from the
      internal stores and/or metallothioneins, also is involved in cognitive activity,
      because zinc-dependent system such as zinc-binding proteins is usually required
      for cognitive process. Intracellular Zn(2+) dynamics may be modified via an
      endocrine system activity, glucocorticoid secretion in both zincergic and
      nonzincergic neurons, which is linked to a long-lasting change in synaptic
      efficacy. On the basis of the evidence of cognitive decline caused by the lack
      and/or the blockade of synaptic Zn(2+) signaling, this article summarizes the
      involvement of intracellular Zn(2+) signaling in zincergic synapses in cognition
      and a hypothetical involvement of that in nonzincergic synapses.

PMID- 24723301
TI  - Different regimens of intravenous sedatives or hypnotics for electroconvulsive
      therapy (ECT) in adult patients with depression.
AB  - BACKGROUND: Depression is a common mental disorder. It affects millions of people
      worldwide and is considered by the World Health Organization (WHO) to be one of
      the leading causes of disability. Electroconvulsive therapy (ECT) is a well
      established treatment for severe depression. Intravenous anaesthetic medication
      is used to minimize subjective unpleasantness and adverse side effects of the
      induced tonic-clonic seizure. The influence of different anaesthetic medications
      on the successful reduction of depressive symptoms and adverse effects is
      unclear. OBJECTIVES: This review evaluated the effects of different regimens of
      intravenous sedatives and hypnotics on anti-depression efficacy, recovery and
      seizure duration in depressed adults undergoing ECT. SEARCH METHODS: We searched
      the Cochrane Central Register of Controlled Trials (CENTRAL) (2012, Issue 12);
      MEDLINE via Ovid SP (from 1966 to 31 December 2012); and EMBASE via Ovid SP (from
      1966 to 31 December 2012). We handsearched related journals and applied no
      language restrictions. SELECTION CRITERIA: We included randomized controlled
      trials (RCTs) and cross-over trials evaluating the effects of different
      intravenous sedatives and hypnotics for ECT. We excluded studies and trials using
      placebo or inhalational anaesthetics and studies that used no anaesthetic. DATA
      COLLECTION AND ANALYSIS: Two review authors independently assessed trial quality
      and extracted data. When possible, data were pooled and risk ratios (RRs) and
      mean differences (MDs), each with 95% confidence intervals (CIs), were computed
      using the Cochrane Review Manager statistical package (RevMan). MAIN RESULTS: We
      included in the review 18 RCTs (599 participants; published between 1994 and
      2012). Most of the included trials were at high risk of bias.We analysed the
      results of studies comparing six different intravenous anaesthetics.Only a few
      studies comparing propofol with methohexital (four studies) and with thiopental
      (three studies) could be pooled.No difference was noted in the reduction of
      depression scores observed in participants treated with propofol compared with
      methohexital (low-quality evidence). These four studies were not designed to
      detect differences in depression scores.The duration of electroencephalograph
      (EEG) and of motor seizures was shorter in the propofol group compared with the
      methohexital group (low-quality evidence). No difference was seen in EEG seizure
      duration when propofol was compared with thiopental (low-quality evidence).Time
      to recovery (following commands) was longer among participants after anaesthesia
      with thiopental compared with propofol (low-quality evidence).For the remaining
      comparisons of anaesthetics, only single studies or insufficient data were
      available. Adverse events were inadequately reported in eligible trials, and none
      of the included trials reported anaesthesia-related mortality. AUTHORS'
      CONCLUSIONS: Most of the included studies were at high risk of bias, and the
      quality of evidence was generally low. The studies were not designed to detect
      clinically relevant differences in depression scores. Anaesthetic agents should
      be chosen on the basis of adverse effect profile, emergence and how these
      medications affect seizure duration. If it is difficult to elicit an adequately
      long seizure, methohexital may be superior to propofol (low-quality evidence). If
      a patient is slow to recover from anaesthesia, propofol may allow a faster time
      to follow commands than thiopental (low-quality evidence). A factor of clinical
      concern that was not addressed by any study was adrenal suppression from
      etomidate. Optimal dosages of intravenous sedatives or hypnotics have not yet
      been determined.Larger well-designed randomized studies are needed to determine
      which intravenous anaesthetic medication leads to the greatest improvement in
      depression scores with minimal adverse effects.

PMID- 24723302
TI  - Prevalence and risk factors of late presentation for HIV diagnosis and care in a
      tertiary referral centre in Switzerland.
AB  - QUESTIONS UNDER STUDY: We sought to identify reasons for late human
      immunodeficiency virus (HIV) testing or late presentation for care. METHODS: A
      structured chart review was performed to obtain data on test- and health-seeking
      behaviour of patients presenting late with CD4 cell counts below 350 cells/ul or
      with acquired immunodeficiency syndrome (AIDS), at the Zurich centre of the Swiss
      HIV Cohort Study between January 2009 and December 2011. Logistic regression
      analyses were used to compare demographic characteristics of persons presenting
      late with not late presenters. RESULTS: Of 281 patients, 45% presented late, 48%
      were chronically HIV-infected non-late presenters, and an additional 7% fulfilled
      the <350 CD4 cells/ul criterion for late presentation but a chart review revealed
      that lymphopenia was caused by acute HIV infection. Among the late presenters,
      60% were first tested HIV positive in a private practice. More than half of the
      tests (60%) were suggested by a physician, only 7% following a specific risk
      situation. The majority (88%) of patients entered medical care within 1 month of
      testing HIV positive. Risk factors for late presentation were older age (odds
      ratio [OR] for >= 50 vs <30 years: 3.16, p = 0.017), Asian versus Caucasian
      ethnicity (OR 3.5, p = 0.021). Compared with men who have sex with men (MSM)
      without stable partnership, MSM in a stable partnership appeared less likely to
      present late (OR 0.50, p = 0.034), whereas heterosexual men in a stable
      partnership had a 2.72-fold increased odds to present late (p = 0.049).
      CONCLUSIONS: The frequency of late testing could be reduced by promoting
      awareness, particularly among older individuals and heterosexual men in stable
      partnerships.

PMID- 24723303
TI  - Acquisition strategy to reduce cerebrospinal fluid partial volume effects for
      improved DTI tractography.
AB  - PURPOSE: An acquisition method that does not increase scan time or specific
      absorption rate is investigated for reducing the deleterious effects of
      cerebrospinal fluid (CSF) partial volume effects on diffusion tensor imaging
      (DTI) tractography. It is based on using a shorter repetition time (TR) by means
      of slice acquisition re-ordering to reduce the signal of long T1 CSF and a non
      zero minimum diffusion weighting (b-value) to attenuate rapidly diffusing CSF
      signal with respect to brain tissue. METHODS: A target reduction of the CSF/brain
      signal ratio from 3.5 to 0.8 required a TR of 2.5 s and minimum b-value of 425
      s/mm(2) . This was evaluated at 4.7 Tesla in eight healthy young adults for
      tractography of the fornix, which has considerable CSF contamination and is
      difficult to track from standard DTI. RESULTS: This method effectively reduced
      CSF signal relative to brain and yielded more robust tractography, increased
      tract volume, increased fractional anisotropy, and decreased mean diffusivity in
      the fornix relative to standard DTI. CONCLUSION: CSF partial volume effects in
      DTI can be mitigated in acquisition through reduced TR and non-zero minimum
      diffusion weighting. The lack of RF absorption rate or scan time increases is
      attractive over other CSF suppression methods such as inversion recovery.

PMID- 24723304
TI  - Surface modification of PDMS microchips with poly(ethylene glycol) derivatives
      for MUTAS applications.
AB  - In this work is presented a method for the modification of native PDMS surface in
      order to improve its applicability as a substrate for microfluidic devices,
      especially in the analysis of nonpolar analytes. Therefore, poly(ethylene glycol)
      divinyl ether modified PDMS substrate was obtained by surface modification of
      native PDMS. The modified substrate was characterized by attenuated total
      reflectance infrared spectroscopy, water contact angle measurements, and by
      evaluating the adsorption of rhodamine B and the magnitude of the EOF mobility.
      The reaction was confirmed by the spectroscopic evaluation. The formation of a
      well-spread water film over the surface immediately after the modification was an
      indicative of the modified surface hydrophilicity. This characteristic was
      maintained for approximately ten days, with a gradual return to a hydrophobic
      state. Fluorescence assays showed that the nonpolar adsorption property of PDMS
      was significantly decreased. The EOF mobility obtained was 3.6 * 10(-4) cm(2) V(
      1) s(-1) , higher than the typical values found for native PDMS. Due to the
      better wettability promoted by the modification, the filling of the microchannels
      with aqueous solutions was facilitated and trapping of air bubbles was not
      observed. 

PMID- 24723307
TI  - Determination of the solubility of crystalline low molar mass compounds in
      polymers by differential scanning calorimetry.
AB  - A mathematical equation has been derived to calculate the liquidus for a binary
      system consisting of an amorphous polymer and a crystalline low molar mass
      compound. The experimental input to this equation is an interaction enthalpy,
      which is derived from the variation of the melting enthalpy with composition in
      differential scanning calorimetry (DSC) experiments. The predictive power of the
      equation has been tested with mixtures of acetylsalicylic acid, carbamazepine, or
      intraconazole with poly(ethylene glycol) as well as mixtures of carbamazepine
      with poly(acrylic acid), poly(hydroxystyrene), or poly(vinylpyrrolidone). It has
      been confirmed that the evaluation of the melting enthalpy in DSC is a suitable
      method to identify the preferred solute-polymer combinations for
      thermodynamically stable molecular dispersions.

PMID- 24723305
TI  - Spreading depression requires microglia and is decreased by their M2a
      polarization from environmental enrichment.
AB  - Microglia play an important role in fine-tuning neuronal activity. In part, this
      involves their production of tumor necrosis factor-alpha (TNFalpha), which
      increases neuronal excitability. Excessive synaptic activity is necessary to
      initiate spreading depression (SD). Increased microglial production of
      proinflammatory cytokines promotes initiation of SD, which, when recurrent, may
      play a role in conversion of episodic to high frequency and chronic migraine.
      Previous work shows that this potentiation of SD occurs through increased
      microglial production of TNFalpha and reactive oxygen species, both of which are
      associated with an M1-skewed microglial population. Hence, we explored the role
      of microglia and their M1 polarization in SD initiation. Selective ablation of
      microglia from rat hippocampal slice cultures confirmed that microglia are
      essential for initiation of SD. Application of minocycline to dampen M1 signaling
      led to increased SD threshold. In addition, we found that SD threshold was
      increased in rats exposed to environmental enrichment. These rats had increased
      neocortical levels of interleukin-11 (IL-11), which decreases TNFalpha signaling
      and polarized microglia to an M2a-dominant phenotype. M2a microglia reduce
      proinflammatory signaling and increase production of anti-inflammatory cytokines,
      and therefore may protect against SD. Nasal administration of IL-11 to mimic
      effects of environmental enrichment likewise increased M2a polarization and
      increased SD threshold, an effect also seen in vitro. Similarly, application of
      conditioned medium from M2a polarized primary microglia to slice cultures also
      increased SD threshold. Thus, microglia and their polarization state play an
      essential role in SD initiation, and perhaps by extension migraine with aura and
      migraine.

PMID- 24723308
TI  - Challenges of "going nano": enhanced electrochemical performance of cobalt oxide
      nanoparticles by carbothermal reduction and in situ carbon coating.
AB  - The electrochemical performance of nano- and micron-sized Co(3)O(4) is
      investigated, highlighting the substantial influence of the specific surface area
      on the obtainable specific capacities as well as the cycling stability. In fact,
      Co(3)O(4) materials with a high surface area (i.e. a small particle size) show
      superior specific features, which are, however, accompanied by a rapid capacity
      fading, owing to the increased formation of an insulating polymeric surface film
      that results from transition-metal-catalyzed electrolyte decomposition. The
      simultaneous coating with carbon of Co(3)O(4) nanoparticles and in situ reduction
      of the Co(3)O(4) by a carbothermal route yields a CoO-Co-C nanocomposite. The
      formation of this material substantially enhances the long-term cycling stability
      and coulombic efficiency of the lithium-ion active material used. Although the
      metallic cobalt enhances the electronic conductivity within the electrode and
      remains electrochemically inactive (as revealed by in situ powder X-ray
      diffraction analysis), it might have a detrimental effect on the long-term
      cycling stability by catalytically inducing continuous electrolyte decomposition.

PMID- 24723306
TI  - Sizing up models of heart failure: Proteomics from flies to humans.
AB  - Cardiovascular disease is the leading cause of death in the western world. Heart
      failure is a heterogeneous and complex syndrome, arising from various etiologies,
      which result in cellular phenotypes that vary from patient to patient. The
      ability to utilize genetic manipulation and biochemical experimentation in animal
      models has made them indispensable in the study of this chronic condition.
      Similarly, proteomics has been helpful for elucidating complicated cellular and
      molecular phenotypes and has the potential to identify circulating biomarkers and
      drug targets for therapeutic intervention. In this review, the use of human
      samples and animal model systems (pig, dog, rat, mouse, zebrafish, and fruit fly)
      in cardiac research is discussed. Additionally, the protein sequence homology
      between these species and the extent of conservation at the level of the phospho
      proteome in major kinase signaling cascades involved in heart failure are
      investigated. 

PMID- 24723311
TI  - Indirect evidence for proton pump inhibitor failure in patients taking them
      independent of meals.
AB  - PURPOSE: We investigated the association between conditions of proton pump
      inhibitor (PPI) treatment failure and food intake in an elderly ambulatory
      population. METHODS: Our data originate from a large population-based cohort
      study. During a home visit done by a trained study physician, patients were asked
      for each medication to state whether it was taken in relation to a meal (before,
      concurrently with, and after) or independent of a meal. This information was
      analyzed for all patients taking a PPI daily and correlated to markers of PPI
      failure. RESULTS: Out of 2717 patients participating in a home visit and taking
      at least one medication, 383 took a PPI daily (14.1%). A PPI intake independent
      of meals was defined as incorrect and was observed in 64 patients, whereas 319
      patients took their PPI in relation to a meal, which was defined as the correct
      intake. Treatment failure was observed in 10 out of 64 (15.6%) PPI users with
      incorrect intake and in 18 out of 319 (5.6%) PPI users with correct intake. The
      risk of treatment failure was threefold higher in patients taking their PPI
      independent of meals (OR 3.35; 95%CI 1.44-7.76). CONCLUSION: The higher risk for
      PPI failure in patients taking PPIs independent of meals suggests that
      synchronized PPI administration with meals is indeed essential, and better
      counseling of patients is needed.

PMID- 24723309
TI  - In vivo whole animal body imaging reveals colonization of Chlamydia muridarum to
      the lower genital tract at early stages of infection.
AB  - PURPOSE: The leading cause of sexually transmitted bacterial infection is
      Chlamydia trachomatis. The aim of this study is to investigate the early events
      in colonization of this bacterium within the murine genital tract. PROCEDURES: An
      in vivo animal body imaging technology was used to track fluorophore labeled C.
      muridarum elementary bodies (EBs) inoculated intravaginally in C57BL/6 mice
      during the first 24 h of infection. RESULTS: Ascension of viable EBs was observed
      (1) to be localized to the lower regions of the murine genital tract within the
      first 24 h post challenge and (2) was dose independent during this early exposure
      period. Molecular detection revealed enhanced bacterial load in lower regions of
      the genital tract with increasing bacterial load in the upper region beginning 12
      h post inoculation. CONCLUSION: This study provides additional insight into
      chlamydial colonization in the murine genital tract during the first 12-24 h
      following inoculation.

PMID- 24723310
TI  - Determination of Sudan dyes in chili pepper powder by online solid-phase
      extraction with a butyl methacrylate monolithic column coupled to liquid
      chromatography with tandem mass spectrometry.
AB  - A poly(butyl methacrylate-co-ethylene dimethacrylate) monolithic column was
      fabricated and used as a novel sorbent for online solid-phase extraction coupled
      to liquid chromatography with tandem mass spectrometry for the simultaneous
      determination of Sudan I-IV in chili pepper powder. The prepared columns were
      characterized by scanning electron microscopy, nitrogen adsorption-desorption,
      and pressure drop measurements. Online solid-phase extraction was performed on
      the synthesized monolithic column using 10 mM ammonium acetate solution as the
      loading solution with the aid of an online cleanup chromatography system. The
      desorption of Sudan I-IV was achieved with acetonitrile as the eluting solution
      at the flow rate of 0.5 mL/min. The extracted analytes were subsequently eluted
      into a C18 analytical column for chromatographic separation using a mixture of
      10% acetonitrile/90% formic acid (0.5%) solution as the mobile phase. Under the
      optimized conditions, the developed method had linear range of 1.0-50 MUg/kg, a
      detection limit of 0.3 MUg/kg, and a quantification limit of 1.0 MUg/kg for each
      analyte. The intraday and interday recoveries of Sudan I-IV in chili pepper
      powder samples ranged from 94.8 to 100.9% and 94.9 to 99.4%, respectively. The
      intraday and interday precision were between 3.37-7.01% and 5.01-7.68%,
      respectively. 

PMID- 24723312
TI  - Cognitive behavioural therapy (brief versus standard duration) for schizophrenia.
AB  - BACKGROUND: Cognitive behavioural therapy for people with schizophrenia is a
      psychotherapeutic approach that establishes links between thoughts, emotions and
      behaviours and challenges dysfunctional thoughts. There is some evidence to
      suggest that cognitive behavioural therapy for people with psychosis (CBTp) might
      be an effective treatment for people with schizophrenia. There are however,
      limitations in its provision due to available resource and training issues. One
      way to tackle this issue might be to offer a brief version of CBTp. OBJECTIVES:
      To review the effects of brief CBTp (6 to 10 regular sessions given in less than
      4 months and using a manual) for people with schizophrenia compared with standard
      CBTp (12 to 20 regular sessions given in 4 to 6 months and using a manual).
      SEARCH METHODS: We searched the Cochrane Schizophrenia Group's Trials Register
      (August 21, 2013) which is based on regular searches of CINAHL, BIOSIS, AMED,
      EMBASE, PubMed, MEDLINE, PsycINFO and registries of Clinical Trials. There are no
      language, date, document type, or publication status limitations for inclusion of
      records in the register. We inspected all references of the selected articles for
      further relevant trials. We also contacted experts in the field regarding brief
      CBTp studies. SELECTION CRITERIA: Randomised controlled trials involving adults
      with schizophrenia or related disorders, comparing brief cognitive behavioural
      therapy for people with psychosis versus standard CBTp. DATA COLLECTION AND
      ANALYSIS: Two review authors independently screened and assessed studies for
      inclusion using pre-specified inclusion criteria. MAIN RESULTS: We found only
      seven studies which used a brief version of CBTp, but no study compared brief
      CBTp with CBTp of standard duration. No studies could be included. AUTHORS'
      CONCLUSIONS: Currently there is no literature available to compare brief with
      standard CBTp for people with schizophrenia. We cannot, therefore, conclude
      whether brief CBTp is as effective, less effective or even more effective than
      standard courses of the same therapy. This lack of evidence for brief CBTp has
      serious implications for research and practice. Well planned, conducted and
      reported randomised trials are indicated.

PMID- 24723313
TI  - GABA-induced uncoupling of GABA/benzodiazepine site interactions is associated
      with increased phosphorylation of the GABAA receptor.
AB  - The use-dependent regulation of the GABAA receptor occurs under physiological,
      pathological, and pharmacological conditions. Tolerance induced by prolonged
      administration of benzodiazepines is associated with changes in GABAA receptor
      function. Chronic exposure of neurons to GABA for 48 hr induces a downregulation
      of the GABAA receptor number and an uncoupling of the GABA/benzodiazepine site
      interactions. A single brief exposure ((t1/2) = 3 min) of rat neocortical neurons
      to the neurotransmitter initiates a process that results in uncoupling hours
      later (t(1/2) = 12 hr) without alterations in the number of GABAA receptors and
      provides a paradigm to study the uncoupling mechanism selectively. Here we report
      that uncoupling induced by a brief GABAA receptor activation is blocked by the
      coincubation with inhibitors of protein kinases A and C, indicating that the
      uncoupling is mediated by the activation of a phosphorylation cascade. GABA
      induced uncoupling is accompanied by subunit-selective changes in the GABAA
      receptor mRNA levels. However, the GABA-induced downregulation of the alpha3
      subunit mRNA level is not altered by the kinase inhibitors, suggesting that the
      uncoupling is the result of a posttranscriptional regulatory process. GABA
      exposure also produces an increase in the serine phosphorylation on the GABAA
      receptor gamma2 subunit. Taken together, our results suggest that the GABA
      induced uncoupling is mediated by a posttranscriptional mechanism involving an
      increase in the phosphorylation of GABAA receptors. The uncoupling of the GABAA
      receptor may represent a compensatory mechanism to control GABAergic
      neurotransmission under conditions in which receptors are persistently activated.

PMID- 24723315
TI  - Response to letter regarding article, "A prospective cohort study of patients
      with transient ischemic attack to identify high-risk clinical characteristics".

PMID- 24723314
TI  - Relative contributions of sympathetic, cholinergic, and myogenic mechanisms to
      cerebral autoregulation.
AB  - BACKGROUND AND PURPOSE: Prior work aimed at improving our understanding of human
      cerebral autoregulation has explored individual physiological mechanisms of
      autoregulation in isolation, but none has attempted to consolidate the individual
      roles of these mechanisms into a comprehensive model of the overall cerebral
      pressure-flow relationship. METHODS: We retrospectively analyzed this
      relationship before and after pharmacological blockade of alpha-adrenergic-,
      muscarinic-, and calcium channel-mediated mechanisms in 43 healthy volunteers to
      determine the relative contributions of the sympathetic, cholinergic, and
      myogenic controllers to cerebral autoregulation. Projection pursuit regression
      was used to assess the effect of pharmacological blockade on the cerebral
      pressure-flow relationship. Subsequently, ANCOVA decomposition was used to
      determine the cumulative effect of these 3 mechanisms on cerebral autoregulation
      and whether they can fully explain it. RESULTS: Sympathetic, cholinergic, and
      myogenic mechanisms together accounted for 62% of the cerebral pressure-flow
      relationship (P<0.05), with significant and distinct contributions from each of
      the 3 effectors. ANCOVA decomposition demonstrated that myogenic effectors were
      the largest determinant of the cerebral pressure-flow relationship, but their
      effect was outside of the autoregulatory region where neurogenic control appeared
      prepotent. CONCLUSIONS: Our results suggest that myogenic effects occur outside
      the active region of autoregulation, whereas neurogenic influences are largely
      responsible for cerebral blood flow control within it. However, our model of
      cerebral autoregulation left 38% of the cerebral pressure-flow relationship
      unexplained, suggesting that there are other physiological mechanisms that
      contribute to cerebral autoregulation.

PMID- 24723316
TI  - Letter by Filis et al regarding article, "Non-ST-elevation myocardial infarction
      in patients undergoing carotid endarterectomy or carotid artery stent placement".

PMID- 24723317
TI  - Letter by Purroy and Kelly regarding article, "A prospective cohort study of
      patients with transient ischemic attack to identify high-risk clinical
      characteristics".

PMID- 24723319
TI  - Recognition memory impairments after subcortical white matter stroke in mice.
AB  - BACKGROUND AND PURPOSE: Small subcortical white matter infarcts are a common
      stroke subtype often associated with cognitive deficits. The lack of relevant
      models confined to white matter has limited the investigation of its
      pathophysiology. Here, we examine tissue and functional outcome after an ischemic
      lesion within corpus callosum in wild-type (WT) mice and in mice null for a gene,
      NOTCH3, linked to white matter ischemic injury in patients. METHODS: WT and
      NOTCH3 knockout mice were subjected to stereotactic microinjections of the potent
      vasoconstrictor endothelin-1 at the level of periventricular white matter to
      induce a focal ischemic lesion. Infarct location was confirmed by MRI, and brains
      were examined for lesion size and histology; behavioral deficits were assessed
      <=1 month in WT mice. RESULTS: Ischemic damage featured an early cerebral blood
      flow deficit, blood-brain barrier opening, and a lesion largely confined to white
      matter. At later stages, myelin and axonal degeneration and microglial/macrophage
      infiltration were found. WT mice displayed prolonged cognitive deficit when
      tested using a novel object recognition task. NOTCH3 mutants showed larger
      infarcts and greater cognitive deficit at 7 days post stroke. CONCLUSIONS: Taken
      together, these data show the usefulness of microinjections of endothelin-1 into
      periventricular white matter to study focal infarcts and cognitive deficit in WT
      mice. In short-term studies, stroke outcome was worse in NOTCH3 null mice,
      consistent with the notion that the lack of the NOTCH3 receptor affects white
      matter stroke susceptibility.

PMID- 24723320
TI  - 3-D reconstruction of neurons from multichannel confocal laser scanning image
      series.
AB  - A confocal laser scanning microscope (CLSM) collects information from a thin,
      focal plane and ignores out-of-focus information. Scanning of a specimen, with
      stepwise axial (Z-) movement of the stage in between each scan, produces Z-series
      of confocal images of a tissue volume, which then can be used to 3-D reconstruct
      structures of interest. The operator first configures separate channels (e.g.,
      laser, filters, and detector settings) for each applied fluorochrome and then
      acquires Z-series of confocal images: one series per channel. Channel signal
      separation is extremely important. Measures to avoid bleaching are vital. Post
      acquisition deconvolution of the image series is often performed to increase
      resolution before 3-D reconstruction takes place. In the 3-D reconstruction
      programs described in this unit, reconstructions can be inspected in real time
      from any viewing angle. By altering viewing angles and by switching channels off
      and on, the spatial relationships of 3-D-reconstructed structures with respect to
      structures visualized in other channels can be studied. Since each brand of CLSM,
      computer program, and 3-D reconstruction package has its own proprietary set of
      procedures, a general approach is provided in this protocol wherever possible.

PMID- 24723321
TI  - Rodent model of activity-based anorexia.
AB  - Activity-based anorexia (ABA) consists of a procedure that involves the
      simultaneous exposure of animals to a restricted feeding schedule, while free
      access is allowed to an activity wheel. Under these conditions, animals show a
      progressive increase in wheel running, a reduced efficiency in food intake to
      compensate for their increased activity, and a severe progression of weight loss.
      Due to the parallelism with the clinical manifestations of anorexia nervosa
      including increased activity, reduced food intake and severe weight loss, the ABA
      procedure has been proposed as the best analog of human anorexia nervosa (AN).
      Thus, ABA research could both allow a better understanding of the mechanisms
      underlying AN and generate useful leads for treatment development in AN.

PMID- 24723322
TI  - The 3-NP Model of Striatal Neurodegeneration.
AB  - The mitochondrial toxin 3-nitropropionic acid (3-NP) is an irreversible inhibitor
      of respiratory chain complex II. Chronic systemic administration of 3-NP to mice,
      rats, and non-human primates leads to preferential degeneration of the striatum,
      and produces motor and cognitive symptoms that are highly reminiscent of
      Huntington's disease (HD). HD is caused by a dominant inherited expansion of CAG
      repeats in the Huntington gene. Thus, many aspects of HD cannot be mimicked by 3
      NP. However, recent research shows that mitochondrial defects and oxidative
      stress may play a key role in HD pathogenesis, further supporting the potential
      utility of the 3-NP model of striatal degeneration. First, a basic protocol to
      produce acute striatal lesions in rats using repeated intraperitoneal injection
      of 3-NP is described. Second, a more complex protocol that takes advantage of the
      use of osmotic minipumps to steadily release 3-NP leading to consistent lesions
      and motor symptoms in Lewis rats is presented.

PMID- 24723323
TI  - Competitive virus and host RNAs: the interplay of a hidden virus and host
      interaction.
AB  - During virus infection, viral RNAs and mRNAs function as blueprints for viral
      protein synthesis and possibly as pathogen-associated molecular patterns (PAMPs)
      in innate immunity. Here, considering recent research progress in microRNAs
      (miRNAs) and competitive endogenous RNAs (ceRNAs), we speculate that viral RNAs
      act as sponges and can sequester endogenous miRNAs within infected cells, thus
      cross-regulating the stability and translational efficiency of host mRNAs with
      shared miRNA response elements. This cross-talk and these reciprocal interactions
      between viral RNAs and host mRNAs are termed "competitive viral and host RNAs"
      (cvhRNAs). We further provide recent experimental evidence for the existence of
      cvhRNAs networks in hepatitis B virus (HBV), as well as Herpesvirus saimiri
      (HVS), lytic murine cytomegalovirus (MCMV) and human cytomegalovirus (HCMV)
      infections. In addition, the cvhRNA hypothesis also predicts possible cross
      regulation between host and other viruses, such as hepatitis C virus (HCV), HIV,
      influenza virus, human papillomaviruses (HPV). Since the interaction between
      miRNAs and viral RNAs also inevitably leads to repression of viral RNA function,
      we speculate that virus may evolve either to employ cvhRNA networks or to avoid
      miRNA targeting for optimal fitness within the host. CvhRNA networks may
      therefore play a fundamental role in the regulation of viral replication,
      infection establishment, and viral pathogenesis. 

PMID- 24723325
TI  - Brief communication: Developmental versus functional three-dimensional geometric
      morphometric-based modularity of the human proximal humerus.
AB  - The proximal humerus is formed by three secondary ossification centers during the
      postnatal trajectory of the human infant. The ossification centers later grow
      into the structures of the articular surface, major tubercle, and minor tubercle.
      There is a purported functional division between the articular surface and the
      tubercles, with the articular surface mainly responsible for the range of
      movement of the shoulder joint, and the tubercles bearing the insertions of the
      rotator cuff muscles, mainly devoted to securing the joint against humeral
      displacement. Using three-dimensional geometric morphometrics, we tested the
      presence of such developmental and functional divisions in the proximal humerus,
      applying the RV coefficient of Escoufier to these a priori hypothesized modules.
      Our results indicate that the proximal humerus might be a generally integrated
      structure. However, a weak signal for modular configuration was present, with
      slightly stronger support for the two modules depicting the boundaries between
      the purported functional regions of the epiphysis: the articular surface and the
      tubercles.

PMID- 24723324
TI  - Aberrant neuronal differentiation and inhibition of dendrite outgrowth resulting
      from endoplasmic reticulum stress.
AB  - Neural stem cells (NSCs) play an essential role in development of the central
      nervous system. Endoplasmic reticulum (ER) stress induces neuronal death. After
      neuronal death, neurogenesis is generally enhanced to repair the damaged regions.
      However, it is unclear whether ER stress directly affects neurogenesis-related
      processes such as neuronal differentiation and dendrite outgrowth. We evaluated
      whether neuronal differentiation and dendrite outgrowth were regulated by HRD1, a
      ubiquitin ligase that was induced under mild conditions of tunicamycin-induced ER
      stress. Neurons were differentiated from mouse embryonic carcinoma P19 cells by
      using retinoic acid. The differentiated cells were cultured for 8 days with or
      without tunicamycin and HRD1 knockdown. The ER stressor led to markedly increased
      levels of ER stress. ER stress increased the expression levels of neuronal marker
      betaIII-tubulin in 8-day-differentiated cells. However, the neurites of dendrite
      marker microtubule-associated protein-2 (MAP-2)-positive cells appeared to
      retract in response to ER stress. Moreover, ER stress markedly reduced the
      dendrite length and MAP-2 expression levels, whereas it did not affect the number
      of surviving mature neurons. In contrast, HRD1 knockdown abolished the changes in
      expression of proteins such as betaIII-tubulin and MAP-2. These results suggested
      that ER stress caused aberrant neuronal differentiation from NSCs followed by the
      inhibition of neurite outgrowth. These events may be mediated by increased HRD1
      expression.

PMID- 24723327
TI  - Design of maleimide-functionalised electrodes for covalent attachment of proteins
      through free surface cysteine groups.
AB  - Mixed two-component monolayers on glassy carbon are prepared by electrochemical
      oxidation of N-(2-aminoethyl)acetamide and mono-N-Boc-hexamethylenediamine in
      mixed solution. Subsequent N-deprotection, amide coupling and solid-phase
      synthetic steps lead to electrode-surface functionalisation with maleimide, with
      controlled partial coverage of this cysteine-binding group at appropriate
      dilution for covalent immobilisation of a model redox-active protein, cytochrome
      c, with high coverage (~7.5 pmol cm(-2) ).

PMID- 24723326
TI  - Discoidin domain receptors: a promoter of the aggressive behavior of
      ameloblastomas.
AB  - Discoidin domain receptors 1 and 2 (DDR1 and DDR2) are members of the receptor
      tyrosine kinases, which regulate fundamental cellular processes concerning
      proliferation, differentiation, adhesion, motility, and apoptosis. The
      dysregulation of these receptors is linked to a number of human diseases,
      including fibrotic disorders, atherosclerosis, and cancer. However, there have
      been no studies that analyzed the expression of these DDRs in ameloblastomas
      (ABs). In this study, we investigated the expression level and distribution of
      both DDRs in ABs and determined whether these receptors could predict the
      prognosis of the disease. Real-time reverse transcription polymerase chain
      reaction, western blot, and immunohistochemical analyses were performed to detect
      the DDR mRNA and protein expression levels in normal oral mucosa (NOM) and ABs.
      The relationship of the DDRs with the clinicopathology and prognosis of ABs was
      analyzed statistically. The mRNA expression levels of DDR1 and DDR2 were found to
      be increased by 3.42- and 3.66-fold in ABs versus NOM, respectively. Recurrent
      ABs displayed higher DDR mRNA expression than did primary ABs (P < 0.05). Using
      western blot analysis, the DDR proteins were found to be lower in NOM than in ABs
      (P < 0.05), and primary ABs showed lower expression levels than did recurrent
      ones (P < 0.05). Immunohistochemically, the DDR protein expressions were markedly
      higher in ABs than in NOM (P < 0.05), and AB patients with higher DDR protein
      expression showed higher recurrence (P < 0.05). Multivariate analysis with the
      Cox proportional hazards model indicated the expression of both DDRs to be an
      independent prognostic factor of ABs. It was suggested that the up-regulation of
      DDR expression might play an important role in the tumorigenesis and
      aggressiveness of ABs. Thus, DDR protein expression may be considered as a good
      biomarker for indicating the prognosis of ABs.

PMID- 24723329
TI  - Sample collection in clinical proteomics--proteolytic activity profile of serum
      and plasma.
AB  - PURPOSE: Proteolytic enzymes are promising diagnostic targets since they play key
      roles in diverse physiological processes and have been implicated in numerous
      human diseases. Human blood is a relatively noninvasive source for disease
      specific protease biomarker detection and subsequent translation into diagnostic
      tests. However, the choice of serum or plasma, and more specifically, which
      anticoagulant to choose in plasma preparation, is important to address in the
      sample preparation phase of biomarker discovery. EXPERIMENTAL DESIGN: We have
      previously utilized a combinatorial library of internally quenched fluorogenic
      probes to successfully map the global proteolytic profiles of various biological
      fluids. In this study, we utilized the platform to ascertain the impact of three
      commonly used anticoagulants (EDTA, heparin, and citrate) on the proteolytic
      activity profile of plasma and serum collected from a healthy Caucasian male.
      RESULTS: Serum and plasma citrate were observed to be most proteolytically
      active, followed by plasma heparin and then plasma EDTA. Detailed analysis of the
      amino acid distribution of motifs cleaved and not cleaved by the samples offered
      significant insights in to active proteolytic components within them. CONCLUSION
      AND CLINICAL RELEVANCE: Broad quantitative comparison of proteolytic profiles of
      these samples revealed several novel insights related to the differential
      substrate recognition of proteases present in these biological fluids.

PMID- 24723330
TI  - Rapid communication: Computational simulation and analysis of a candidate for the
      design of a novel silk-based biopolymer.
AB  - This work theoretically investigates the mechanical properties of a novel silk
      derived biopolymer as polymerized in silico from sericin and elastin-like
      monomers. Molecular Dynamics simulations and Steered Molecular Dynamics were the
      principal computational methods used, the latter of which applies an external
      force onto the system and thereby enables an observation of its response to
      stress. The models explored herein are single-molecule approximations, and
      primarily serve as tools in a rational design process for the preliminary
      assessment of properties in a new material candidate.

PMID- 24723328
TI  - Quantification of peptides from immunoglobulin constant and variable regions by
      LC-MRM MS for assessment of multiple myeloma patients.
AB  - PURPOSE: Quantitative MS assays for Igs are compared with existing clinical
      methods in samples from patients with plasma cell dyscrasias, for example,
      multiple myeloma (MM). EXPERIMENTAL DESIGN: Using LC-MS/MS data, Ig constant
      region peptides, and transitions were selected for LC-MRM MS. Quantitative assays
      were used to assess Igs in serum from 83 patients. RNA sequencing and peptide
      based LC-MRM are used to define peptides for quantification of the disease
      specific Ig. RESULTS: LC-MRM assays quantify serum levels of Igs and their
      isoforms (IgG1-4, IgA1-2, IgM, IgD, and IgE, as well as kappa (kappa) and lambda
      (lambda) light chains). LC-MRM quantification has been applied to single samples
      from a patient cohort and a longitudinal study of an IgE patient undergoing
      treatment, to enable comparison with existing clinical methods. Proof-of-concept
      data for defining and monitoring variable region peptides are provided using the
      H929 MM cell line and two MM patients. CONCLUSIONS AND CLINICAL RELEVANCE: LC-MRM
      assays targeting constant region peptides determine the type and isoform of the
      involved Ig and quantify its expression; the LC-MRM approach has improved
      sensitivity compared with the current clinical method, but slightly higher inter
      assay variability. Detection of variable region peptides is a promising way to
      improve Ig quantification, which could produce a dramatic increase in sensitivity
      over existing methods, and could further complement current clinical techniques.

PMID- 24723331
TI  - Thermally induced increase in energy transport capacity of silkworm silks.
AB  - This work reports on the first study of thermally induced effect on energy
      transport in single filaments of silkworm (Bombyx mori) fibroin degummed mild
      (type 1), moderate (type 2), to strong (type 3). After heat treatment from 140 to
      220 degrees C, the thermal diffusivity of silk fibroin type 1, 2, and 3 increases
      up to 37.9, 20.9, and 21.5%, respectively. Our detailed scanning electron
      microscopy study confirms that the sample diameter change is almost negligible
      before and after heat treatment. Raman analysis is performed on the original and
      heat-treated (at 147 degrees C) samples. After heat treatment at 147 degrees C,
      the Raman peaks at 1081, 1230, and 1665 cm(-1) become stronger and narrower,
      indicating structural transformation from amorphous to crystalline. A structure
      model composed of amorphous, crystalline, and laterally ordered regions is
      proposed to explain the structural change by heat treatment. Owing to the close
      packing of more adjacent laterally ordered regions, the number and size of the
      crystalline regions of Bombyx mori silk fibroin increase by heat treatment. This
      structure change gives the observed significant thermal diffusivity increase by
      heat treatment.

PMID- 24723332
TI  - Asiatic acid reduces blood pressure by enhancing nitric oxide bioavailability
      with modulation of eNOS and p47phox expression in L-NAME-induced hypertensive
      rats.
AB  - We investigated the effect of asiatic acid (AA) on hemodynamic status, vascular
      function, oxidative stress markers, endothelial nitric oxide synthase (eNOS), and
      nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunit expression in
      Nomega-nitro-L-arginine methyl ester hydrochloride (L-NAME)-induced hypertensive
      rats. Male Sprague-Dawley rats treated with L-NAME (40 mg/kg/day) in drinking
      water for 5 weeks showed significant increases in mean arterial pressure, heart
      rate, hindlimb vascular resistance, vascular dysfunction, superoxide anion (O2(*
      )) production, and plasma malondialdehyde. Moreover, NO metabolite (NOx) levels
      were reduced, aortic eNOS expression was downregulated, and NADPH oxidase subunit
      p47(phox) was upregulated in hypertensive rats (p < 0.05). Hypertensive rats that
      were administered AA (10 or 20 mg/kg/day) for the last 2 weeks of the study
      showed significant improvement in hemodynamic status and vascular function. The
      antihypertensive effects of AA were associated with elevated plasma NOx levels,
      together with upregulation of eNOS expression. Decreased vascular O2(*-)
      production, consistent with downregulation of p47(phox) expression, was also
      observed after AA treatment. Our results are therefore consistent with a model
      whereby AA reduces blood pressure by enhancing NO bioavailability.

PMID- 24723334
TI  - High-intensity focused ultrasound applied to the placenta using a toroidal
      transducer: a preliminary ex-vivo study.
AB  - OBJECTIVE: To demonstrate in an ex-vivo model the feasibility of applying high
      intensity focused ultrasound (HIFU) using a toroidal transducer for the creation
      of placental lesions. METHODS: In this study we used a toroidal transducer,
      composed of 32 ring-shaped emitters with an ultrasound probe at the center,
      operating at a frequency of 2.5 MHz. We examined 45 human placentae, following
      either normal vaginal delivery or medical termination of pregnancy between 17 and
      40 gestational weeks. First, the attenuation coefficients of 12 human placentae
      were measured and integrated into a numerical model for simulating HIFU lesions.
      Then, using acoustic parameters from this preliminary study, we performed ex-vivo
      experiments with 33 human placentae, each overlain with an animal abdominal wall
      to simulate the maternal wall. We created single HIFU lesions in 25 of these
      placentae, and a series of six juxtaposed lesions in eight, studying these both
      sonographically and macroscopically. RESULTS: Human placental attenuation
      coefficients of the 12 human placentae ranged from 0.072 to 0.098 Np/cm/MHz,
      according to gestational age. The 25 single HIFU lesions created had an average
      diameter of 7.1 +/- 3.2 mm and an average depth of 8.2 +/- 3.1 mm. The average
      diameter of the eight series of six juxtaposed HIFU lesions was 23.0 +/- 5.0 mm
      and the average depth was 11.0 +/- 4.7 mm. The average thickness of the abdominal
      walls was 10.5 +/- 1.8 mm. No lesions or damage were observed in intervening
      tissues. CONCLUSION: This study demonstrates, using an ex-vivo model, the
      feasibility, reproducibility, harmlessness and effectiveness of HIFU applied to
      the human placenta.

PMID- 24723333
TI  - Relative stability of G-quadruplex structures: Interactions between the human
      Bcl2 promoter region and derivatives of carbazole and diphenylamine.
AB  - The bcl2 promoter region forms a G-quadruplex structure, which is a crucial
      target for anticancer drug development. In this study, we provide theoretical
      predictions of the stability of different G-quadruplex folds of the 23-mer bcl2
      promoter region and G-quadruplex ligand. We take into account the whole G
      quadruplex structure, including bound-cations and solvent effects, in order to
      compute the ligand binding free energy using molecular dynamics simulation. Two
      series of the carbazole and diphenylamine derivatives are used to screen for the
      most potent drug in terms of stabilization. The energy analysis identifies the
      predominant energy components affecting the stability of the various different G
      quadruplex folds. The energy associated with the stability of the G-quadruplex
      K(+) structures obtained displays good correlation with experimental Tm
      measurements. We found that loop orientation has an intrinsic influence on G
      quadruplex stability and that the basket structure is the most stable.
      Furthermore, parallel loops are the most effective drug binding site. Our studies
      also demonstrate that rigidity and planarity are the key structural elements of a
      drug that stabilizes the G-quadruplex structure. BMVC-4 is the most potential G
      quadruplex ligand. This approach demonstrates significant promise and should
      benefit drug design.

PMID- 24723335
TI  - Associations of drug burden index with falls, general practitioner visits, and
      mortality in older people.
AB  - AIM: On a population level in people aged >=65 years old living in New Zealand,
      the aim of this study is to quantify each individual's cumulative exposure to
      anticholinergic and sedative medicines using the Drug Burden Index (DBI) and
      examine the impact of DBI on fall-related hospitalisations, general practitioner
      (GP) visits, and all-cause mortality. METHOD: The study used data extracted from
      Pharmaceutical Claims Data Mart (2011), National Minimum Data set (2012), Births,
      Death and Marriages (2012) and GP Visits (2012) for patient demographics,
      hospitalisations and mortality. Cumulative anticholinergic and sedative exposure
      was measured using the DBI. Polypharmacy was defined as greater than or equal to
      five medicines dispensed concurrently at any time during the study period.
      RESULTS: Amongst the study population (n = 537,387; 45% male), 43.22% were
      exposed to DBI drugs (95% confidence intervals (CIs) = 43.09-43.35). The odds of
      DBI exposure for individuals with polypharmacy are 4.92 (95%CI = 4.86-4.98) times
      greater than that for individuals without polypharmacy. DBI drugs were associated
      with fall-related hospitalisations (incidence rate ratio (IRR) 1.56, 95%CI = 1.47
      1.65) and greater number of GP visits (IRR 1.13, 95%CI = 1.12-1.13). Individuals
      with DBI > 0 had a 1.29 times higher mortality risk (95%CI = 1.25-1.33).
      Polypharmacy is also associated with a higher mortality risk with a hazard ratio
      (HR) of 1.66 (95%CI = 1.59-1.73). CONCLUSION: Polypharmacy and exposure to DBI
      drugs were independently associated with fall-related hospitalisations, frequency
      of GP visits, and risk of mortality. On a population level, DBI may be useful as
      a quality indicator to guide policy to improve prescribing and optimize clinical
      outcomes in older people.

PMID- 24723336
TI  - A systematic review of spousal couple-based intervention studies for couples
      coping with cancer: direction for the development of interventions.
AB  - OBJECTIVE: With the research focus on family caregiving shifting from the
      individual to the dyadic level, it is suggested that the caregiver-patient dyad
      as a unit be the focus and direction of caregiving interventions for families
      coping with cancer. The objectives in conducting this review were to explore the
      existing interventions for spousal couples coping with cancer in terms of type of
      intervention, contents, approach, and outcome measurements; and to identify
      directions for the development of interventions. METHODS: A systematic search of
      four databases was conducted to identify articles published in English or Chinese
      from the launch of the databases to March 2013. Studies were located using an
      electronic search, a manual search, and an author search. RESULTS: A total of 17
      articles were identified and included in this review. These interventions focused
      mainly on patient caregiving and caregiver self care, and usually lasted for 6
      weeks using a face-to-face group mode, with follow-up at around 3 months. The
      outcome measures can be grouped into three main dimensions: dyadic appraisal,
      dyadic coping, and dyadic adjustments. Positive outcomes were reported for these
      interventions, including improvements in communication, dyadic coping, the
      quality of life of both the patients and their partners, psychosocial distress,
      sexual functioning, and marital satisfaction. CONCLUSIONS: These findings
      highlighted the positive outcomes of couple-based interventions that focus on
      couples coping with cancer. Future studies on couple-based interventions should
      be conducted in different cultures, such as in Asian countries. Collaboration
      between researchers and clinicians is crucial to ensure the development of
      effective and accessible supportive interventions targeting couples coping with
      cancer.

PMID- 24723337
TI  - Prolonged in vivo imaging of Xenopus laevis.
AB  - BACKGROUND: While live imaging of embryonic development over long periods of time
      is a well established method for embryos of the frog Xenopus laevis, once
      development has progressed to the swimming stages, continuous live imaging
      becomes more challenging because the tadpoles must be immobilized. Current
      imaging techniques for these advanced stages generally require bringing the
      tadpoles in and out of anesthesia for short imaging sessions at selected time
      points, severely limiting the resolution of the data. RESULTS: Here we
      demonstrate that creating a constant flow of diluted tricaine methanesulfonate
      (MS-222) over a tadpole greatly improves their survival under anesthesia. Based
      on this result, we describe a new method for imaging stage 48 to 65 X. laevis, by
      circulating the anesthetic using a peristaltic pump. This supports the animal
      during continuous live imaging sessions for at least 48 hr. The addition of a
      stable optical window allows for high quality imaging through the anesthetic
      solution. CONCLUSIONS: This automated imaging system provides for the first time
      a method for continuous observations of developmental and regenerative processes
      in advanced stages of Xenopus over 2 days. Developmental Dynamics 243:1011-1019,
      2014. (c) 2014 Wiley Periodicals, Inc.

PMID- 24723338
TI  - Separation and characterization of phlorotannins from brown algae Cystoseira
      abies-marina by comprehensive two-dimensional liquid chromatography.
AB  - Phlorotannins are an important class of polyphenolic compounds only found in
      brown algae. The chemical analysis of these bioactive polyphenols is rather
      difficult due to the great chemical variability and complexity of the natural
      composition of these components in algae, forming large phloroglucinol polymers.
      In the present work, a new approach based on the use of comprehensive 2D LC (LC *
      LC) is shown to analyze this complex family of compounds. The developed LC * LC
      methodology is based on the coupling of a hydrophilic-interaction LC (HILIC)
      based separation in the first dimension and an RP-based separation in the second
      dimension. The employment of this online coupling together with DAD and MS/MS
      allowed the separation and identification of more than 50 compounds in a
      Cystoseira abies-marina brown alga extract. Phlorotannins containing from 5 to 17
      phloroglucinol units were identified in this sample by HILIC * RP-DAD-MS/MS.
      Besides, using the 2,4-dimethoxybenzaldehyde assay, it was possible to determine
      that the total amount of phlorotannins present in the extract was 40.2 mg
      phloroglucinol equivalents per gram of extract. To our knowledge, this work is
      the first demonstration of the usefulness of HILIC * RP-DAD-MS/MS for the
      determination of phlorotannins. 

PMID- 24723339
TI  - The ENCODE project and perspectives on pathways.
AB  - The recently completed ENCODE project is a new source of information on metabolic
      activity, unveiling knowledge about evolution and similarities among species,
      refuting the myth that most DNA is "junk" and has no actual function. With this
      expansive resource comes a challenge: integrating these new layers of information
      into our current knowledge of single-nucleotide polymorphisms and previously
      described metabolic pathways with the aim of discovering new genes and pathways
      related to human diseases and traits. Further, we must determine which
      computational methods will be most useful in this pursuit. In this paper, we
      speculate over the possible methods that will emerge in this new, challenging
      field. 

PMID- 24723340
TI  - Reinforcer magnitude and resistance to disruption of forgetting functions and
      response rates.
AB  - The present experiment investigated the effects of reinforcer magnitude on
      resistance to disruption of remembering and response rates. Pigeons were exposed
      to a variable-interval (VI), delayed-matching-to-sample (DMTS) procedure with two
      components (rich and lean, distinguished by differing discriminative stimuli and
      hopper presentation duration). Completion of a VI 20 s schedule resulted in DMTS
      trials. In a DMTS trial, a choice of one of two comparison stimuli resulted in
      food if the choice matched the color of the previously presented sample stimulus.
      Separable aspects of the forgetting functions (initial discrimination and rate of
      forgetting) were examined by determining accuracy across a range of delays.
      Response rates and accuracy were higher in the rich relative to the lean
      component during baseline, and were more persistent during disruptors (extinction
      and prefeeding). During DMTS trials, extinction decreased initial discrimination
      more in the lean than the rich component, but had no systematic effect on rate of
      forgetting. During prefeeding, the rate of forgetting increased more in the lean
      than the rich component, but initial discrimination was not systematically
      affected. These results show persistence of response rates and remembering are
      positively related to reinforcer magnitude. The type of disruptor also influences
      the way in which remembering is disrupted. 

PMID- 24723341
TI  - Valid Monte Carlo permutation tests for genetic case-control studies with missing
      genotypes.
AB  - Monte Carlo permutation tests can be formally constructed by choosing a set of
      permutations of individual indices and a real-valued test statistic measuring the
      association between genotypes and affection status. In this paper, we develop a
      rigorous theoretical framework for verifying the validity of these tests when
      there are missing genotypes. We begin by specifying a nonparametric probability
      model for the observed genotype data in a genetic case-control study with
      unrelated subjects. Under this model and some minimal assumptions about the test
      statistic, we establish that the resulting Monte Carlo permutation test is exact
      level alpha if (1) the chosen set of permutations of individual indices is a
      group under composition and (2) the distribution of the observed genotype score
      matrix under the null hypothesis does not change if the assignment of individuals
      to rows is shuffled according to an arbitrary permutation in this set. We apply
      these conditions to show that frequently used Monte Carlo permutation tests based
      on the set of all permutations of individual indices are guaranteed to be exact
      level alpha only for missing data processes satisfying a rather restrictive
      additional assumption. However, if the missing data process depends on covariates
      that are all identified and recorded, we also show that Monte Carlo permutation
      tests based on the set of permutations within strata of individuals with
      identical covariate values are exact level alpha. Our theoretical results are
      verified and supplemented by simulations for a variety of missing data processes
      and test statistics. 

PMID- 24723342
TI  - The zinc finger gene Fezf2 is required for the development of excitatory neurons
      in the basolateral complex of the amygdala.
AB  - BACKGROUND: The basolateral complex, comprised of the lateral, basolateral, and
      basomedial nuclei, is the main structure of the amygdala and contains two
      neuronal cell types: excitatory neurons and inhibitory interneurons. Studies show
      that most of the excitatory neurons originate in the ventral pallium of the
      telencephalon. However, their subsequent development remains poorly understood.
      RESULTS: In this study, we examined the roles of the zinc finger gene Fezf2 in
      the development of the amygdala. Fezf2 is expressed in the lateral and
      basolateral nuclei during development. In Fezf2-deficient embryos, specific
      excitatory neuron markers in the lateral and basolateral nuclei were reduced,
      with concurrent induction of other markers in the endopiriform cortex.
      Furthermore, the morphology of the lateral and basolateral nuclei was abnormal.
      In the adult stages, excitatory neurons in the lateral and basolateral nuclei
      were greatly reduced because of apoptosis that occurred soon after birth.
      CONCLUSIONS: These results suggest that Fezf2 is required for the development of
      excitatory neurons and nuclear morphology in the lateral and basolateral nuclei,
      and that abnormal formation of these regions leads to cell death soon after birth
      in Fezf2-deficient mice.

PMID- 24723343
TI  - Biomarker discovery for neuroendocrine cervical cancer.
AB  - Neuroendocrine cervical cancer is an aggressive but rare form of cervical cancer.
      The majority of neuroendocrine cervical cancer patients present with advanced
      stage diseases. However, the limited numbers of neuroendocrine tumor markers are
      insufficient for clinical purposes. Thus, we used a proteomic approach combining
      lysine labeling 2D-DIGE and MALDI-TOF MS to investigate the biomarkers for
      neuroendocrine cervical cancer. By analyzing the global proteome alteration
      between the neuroendocrine cervical cancer line (HM-1) and non-neuroendocrine
      cervical cancer lines (CaSki cells, ME-180 cells, and Hela cells), we identified
      82 proteins exhibiting marked changes between HM-1 and CaSki cells, and between
      ME-180 and Hela cells. Several proteins involved in protein folding,
      cytoskeleton, transcription control, signal transduction, glycolysis, and redox
      regulation exhibited significant changes in abundance. Proteomic and immunoblot
      analyses indicated respective 49.88-fold and 25-fold increased levels of
      transgelin in HM-1 cells compared with that in other non-neuroendocrine cervical
      cancer cell lines, implying that transgelin is a biomarker for neuroendocrine
      cervical cancer. In summary, we used a comprehensive neuroendocrine/non
      neuroendocrine cervical cancer model based proteomic approach for identifying
      neuroendocrine cervical cancer markers, which might contribute to the prognosis
      and diagnosis of neuroendocrine cervical cancer.

PMID- 24723344
TI  - Sources and characteristics of carbonaceous aerosols at Agra "World heritage
      site" and Delhi "capital city of India".
AB  - Agra, one of the oldest cities "World Heritage site", and Delhi, the capital city
      of India are both located in the border of Indo-Gangetic Plains (IGP) and heavily
      loaded with atmospheric aerosols due to tourist place, anthropogenic activities,
      and its topography, respectively. Therefore, there is need for monitoring of
      atmospheric aerosols to perceive the scenario and effects of particles over
      northern part of India. The present study was carried out at Agra (AGR) as well
      as Delhi (DEL) during winter period from November 2011 to February 2012 of fine
      particulate (PM2.5: d < 2.5 MUm) as well as associated carbonaceous aerosols.
      PM2.5 was collected at both places using medium volume air sampler (offline
      measurement) and analyzed for organic carbon (OC) and elemental carbon (EC).
      Also, simultaneously, black carbon (BC) was measured (online) at DEL. The average
      mass concentration of PM2.5 was 165.42 +/- 119.46 MUg m(-3) at AGR while at DEL
      it was 211.67 +/- 41.94 MUg m(-3) which is ~27% higher at DEL than AGR whereas
      the BC mass concentration was 10.60 MUg m(-3). The PM2.5 was substantially higher
      than the annual standard stipulated by central pollution control board and United
      States Environmental Protection Agency standards. The average concentrations of
      OC and EC were 69.96 +/- 34.42 and 9.53 +/- 7.27 MUm m(-3), respectively. Total
      carbon (TC) was 79.01 +/- 38.98 MUg m(-3) at AGR, while it was 50.11 +/- 11.93
      (OC), 10.67 +/- 3.56 MUg m(-3) (EC), and 60.78 +/- 14.56 MUg m(-3) (TC) at DEL.
      The OC/EC ratio was 13.75 at (AGR) and 5.45 at (DEL). The higher OC/EC ratio at
      Agra indicates that the formation of secondary organic aerosol which emitted from
      variable primary sources. Significant correlation between PM2.5 and its
      carbonaceous species were observed indicating similarity in sources at both
      sites. The average concentrations of secondary organic carbon (SOC) and primary
      organic carbon (POC) at AGR were 48.16 and 26.52 MUg m(-3) while at DEL it was
      38.78 and 27.55 MUg m(-3), respectively. In the case of POC, similar
      concentrations were observed at both places but in the case of SOC higher over
      AGR by 24 in comparison to DEL, it is due to the high concentration of OC over
      AGR. Secondary organic aerosol (SOA) was 42% higher at AGR than DEL which
      confirms the formation of secondary aerosol at AGR due to rural environment with
      higher concentrations of coarse mode particles. The SOA contribution in PM2.5 was
      also estimated and was ~32 and 12% at AGR and DEL respectively. Being high
      loading of fine particles along with carbonaceous aerosol, it is suggested to
      take necessary and immediate action in mitigation of the emission of carbonaceous
      aerosol in the northern part of India.

PMID- 24723345
TI  - Degrading a mixture of three textile dyes using photo-assisted electrochemical
      process with BDD anode and O2-diffusion cathode.
AB  - In this paper, degradation of a mixture of three azo dyes was studied by the
      photo-assisted electrochemical process using an O2-diffusion cathode containing
      carbon nanotubes and boron-doped diamond (BDD) anode. The concentration of three
      textile dyes (C.I. Acid Orange 8 (AO8), C.I. Acid Orange 10 (AO10), and C.I. Acid
      Orange 12 (AO12)) was determined simultaneously despite the severe overlap of
      their spectra. For this purpose, partial least square (PLS), as a multivariate
      calibration method, was utilized based on recording UV-Vis spectra during the
      decolorization process. Moreover, the central composite design was used for the
      modeling of photo-assisted electrochemical decolorization of the aqueous
      solutions containing three dyes. The investigated parameters were the initial
      concentration of three dyes, applied current and reaction time. Analysis of
      variance (ANOVA) revealed that the obtained regression models match the
      experimental results well with R (Khataee et al. 2010, Clean-Soil Air Water 38
      (1):96-103, 2010) of 0.972, 0.971, and 0.957 for AO8, AO10, and AO12,
      respectively. Three-dimensional surface and contour plots were applied to
      describe the relation between experimental conditions and the observed response.
      The results of TOC analysis confirmed good ability of proposed photo-assisted
      electrochemical process for degradation and mineralization of textile industry
      wastewater.

PMID- 24723346
TI  - Seasonal variation of PCDD/Fs in the metropolis of Istanbul, Turkey.
AB  - Atmospheric concentrations of polychlorinated dibenzo-p-dioxins and dibenzofurans
      (PCDD/F) compounds were investigated at three different regions of Istanbul which
      reflect urban, urban/industrial, and sub-urban characteristics. Air samples were
      collected simultaneously for both gaseous and particulate phases using high
      volume samplers on monthly time intervals from May 2011 to October 2012. The
      highest concentrations (3,056 fg/m(3) and 156 fg I-TEQ/m(3)) were observed at the
      sampling site that reflects traffic, residential, and industrial emission source
      characteristics, while the lowest concentrations (829 fg/m(3) and 38 fg I
      TEQ/m(3)) were observed at the sampling point which is far away from centrum and
      reflects sub-urban characteristics. Concentrations of PCDD congeners were, in
      general, found to be higher than PCDF congeners, and OCDD, 1,2,3,4,6,7,8-HpCDD/F,
      and OCDF congeners were recorded to be the most abundant congeners. Winter season
      concentrations were also found to be higher especially in particulate phase. As a
      result, combustion processes such as motor vehicles and residential heating
      equipment were thought to be the principal sources of emissions of PCDD/F
      compounds when both congener profiles and seasonal variations are considered.
      Basic statistical evaluation of the data resembled high degree of inverse
      correlations between PCDD/F concentrations and UV and solar radiation.

PMID- 24723347
TI  - Investigation of insecticide leaching from potted nursery stock and aquatic
      health benefits of bioretention cells receiving nursery runoff.
AB  - Tree nurseries and greenhouses within the USDA red imported fire ant (RIFA)
      quarantine zone are required to incorporate insecticides into their potting media
      to prevent artificial spread of RIFA. Bifenthrin and fipronil are two common
      insecticides that are incorporated into potting media. During irrigation and
      stormwater events, there is potential for insecticides to leach from nursery
      pots, resulting in the contamination of nearby surface waters. In this study,
      occurrences of insecticides in simulated nursery runoff were compared with two
      irrigation strategies and two types of containers in single pot leaching and
      field runoff simulations. In addition, toxicity of pot leachate to the aquatic
      invertebrate, Hyallela azteca, was measured, and removal efficiencies of
      insecticides from bioretention cell media were evaluated. Overhead irrigation
      resulted in significantly higher concentrations than drip irrigation, and
      RootMaker pots allowed more leaching as compared to standard slick-wall pots.
      However, in all tests, the average concentration of bifenthrin during 15 days of
      leaching in both pot and field simulations was greater than 200 ng/L; more than
      100-fold greater than the LC50 for H. azteca. Toxicity studies confirmed this
      level of toxicity. Higher amounts of compost, 20 and 40%, in bioretention cell
      media resulted in greater percent reduction of both bifenthrin and fipronil. This
      study determined that management techniques may be able to limit the amount of
      insecticide that leaches from pots and runs off to receiving water bodies.
      Specifically, the selection of appropriate pot types, irrigation strategies, or
      filtering runoff through bioretention cells may reduce contamination loads. Thus,
      further best management strategies such as the use of bioretention cells are
      needed in nursery and greenhouse facilities to prevent surface water runoff from
      transporting toxic insecticides.

PMID- 24723348
TI  - Acetamide hydrolyzing activity of Bacillus megaterium F-8 with bioremediation
      potential: optimization of production and reaction conditions.
AB  - Bacillus megaterium F-8 exhibited an intracellular acetamide hydrolyzing activity
      (AHA) when cultivated in modified nutrient broth with 3% tryptone, 1.5% yeast
      extract, and 0.5% sodium chloride, at pH 7.2, 45  degrees C for 24 h. Maximum AHA
      was recorded in the culture containing 0.1 M of sodium phosphate buffer, (pH 7.5)
      at 45  degrees C for 20 min with 0.2 % of acetonitrile and resting cells of B.
      megaterium F-8 equivalent to 0.2 ml culture broth. This activity was stable up to
      55  degrees C and was completely inactivated at or above 60  degrees C. Maximum
      acyl transferase activity (ATA) was recorded in the reaction medium containing
      0.1 M of potassium phosphate buffer, (pH 8.0) at 55  degrees C for 5 min with
      0.85 mM of acetamide as acyl donor and hydroxylamine hydrochloride as acyl
      acceptor and resting cells of B. megaterium F-8 equivalent to 0.94 mg cells (dry
      weight basis). This activity was stable up to 60  degrees C and a rapid decline
      in enzyme activity was recorded above it. Under the optimized conditions, this
      organism hydrolyzed various nitriles and amides such as propionitrile,
      propionamide, caprolactam, acetamide, and acrylamide to corresponding acids. Acyl
      group transfer capability of this organism was used for the production of
      acetohydroxamic acid. ATA of B. megaterium F-8 showed broad substrate specificity
      such as for acetamide followed by propionamide, acrylamide, and lactamide. This
      amide hydrolyzing and amidotransferase activity of B. megaterium F-8 has
      potential applications in enzymatic synthesis of hydroxamic acids and
      bioremediation of nitriles and amides contaminated soil and water system.

PMID- 24723349
TI  - Assessment of silver nanoparticle-induced physiological and molecular changes in
      Arabidopsis thaliana.
AB  - In this study, the effect of silver nanoparticles and silver ions on Arabidopsis
      thaliana was investigated at physiological and molecular levels. The seedlings
      were grown in sublethal concentrations of silver nanoparticles and silver ions
      (0.2, 0.5, and 1 mg/L) in 1/4 Hoagland's medium for 14 days under submerged
      hydroponic conditions. Significantly higher reduction in the total chlorophyll
      and increase in anthocyanin content were observed after exposure to 0.5 and 1
      mg/L silver nanoparticles as compared to similar concentrations of silver ions.
      Lipid peroxidation increased significantly after exposure to 0.2, 0.5, and 1 mg/L
      of silver nanoparticles and 0.5 and 1 mg/L of silver ions. Qualitative analysis
      with dichloro-dihydro-fluorescein diacetate and rhodamine 123 fluorescence showed
      a dose-dependent increase in reactive oxygen species production and changes in
      mitochondrial membrane potential in the roots of seedlings exposed to different
      concentrations of silver nanoparticles. Real-time PCR analysis showed significant
      upregulation in the expression of sulfur assimilation, glutathione biosynthesis,
      glutathione S-transferase, and glutathione reductase genes upon exposure to
      silver nanoparticles as compared with silver ions. Overall, based on the
      physiological and molecular level responses, it was observed that exposure to
      silver nanoparticles exerted more toxic response than silver ions in A. thaliana.

PMID- 24723350
TI  - Function of bacterial cells and their exuded extracellular polymeric substances
      (EPS) in virus removal by red soils.
AB  - The potential influence of autochthonous microorganisms on virus fate in soil is
      usually determined through extreme conditions of sterilization vs.
      nonsterilization; however, the relative importance of microbial cells and their
      exudates remains unclear. In this study, bacterial cells (cell) were harvested,
      and their exuded extracellular polymeric substances (EPS) were extracted from
      three strains of bacteria, namely, Gram-negative bacteria Pseudomonas putida and
      Pseudomonas aeruginosa as well as Gram-positive bacterium Bacillus subtilis. This
      study aimed to evaluate virus removal in solutions in the presence of cell, EPS,
      and their combination (cell/EPS), as well as to investigate how their presence
      affects virus removal efficiencies by four red soils based on batch experiments.
      Results showed that virus removal percentage in solutions ranged from 11 to 23 in
      the presence of cells only and from 12 to 15 in the presence of EPS only. The
      removal percentage in the combined cell/EPS treatment can be estimated by summing
      the results achieved by the cell and EPS treatments, separately. Meanwhile, cell
      presence had a negligible effect on virus removal by red soils. EPS and combined
      cell/EPS significantly reduced virus removal by 20 to 69% and 16 to 50%,
      respectively, which indicated that EPS served a dominant function in reducing
      virus removal. This study clearly demonstrated that the prediction of virus
      removal by red soils must consider the effect of bacteria, especially those
      producing large quantities of EPS, which can be responsible for the
      underestimation of viral load in certain studies.

PMID- 24723351
TI  - Simultaneous decontamination of cross-polluted soils with heavy metals and PCBs
      using a nano-metallic Ca/CaO dispersion mixture.
AB  - In the present work, we investigated the use of nano-metallic calcium (Ca) and
      calcium oxide (CaO) dispersion mixture for the simultaneous remediation of
      contaminated soils with both heavy metals (As, Cd, Cr, and Pb) and
      polychlorinated biphenyls (PCBs). Regardless of soil moisture content, nano
      metallic Ca/CaO dispersion mixture achieved about 95-99% of heavy metal
      immobilization by a simple grinding process. During the same treatment,
      reasonable PCB hydrodechlorination efficiencies were obtained (up to 97%), though
      higher hydrodechlorination efficiency by preliminary drying of soil was observed.

PMID- 24723352
TI  - Formation of indoor nitrous acid (HONO) by light-induced NO2 heterogeneous
      reactions with white wall paint.
AB  - Gaseous nitrogen dioxide (NO2) represents an oxidant that is present in
      relatively high concentrations in various indoor settings. Remarkably increased
      NO2 levels up to 1.5 ppm are associated with homes using gas stoves. The
      heterogeneous reactions of NO2 with adsorbed water on surfaces lead to the
      generation of nitrous acid (HONO). Here, we present a HONO source induced by
      heterogeneous reactions of NO2 with selected indoor paint surfaces in the
      presence of light (300 nm<lambda<400 nm). We demonstrate that the formation of
      HONO is much more pronounced at elevated relative humidity. In the presence of
      light (5.5 W m(-2)), an increase of HONO production rate of up to 8.6.10(9)
      molecules cm(-2) s(-1) was observed at [NO2]=60 ppb and 50% relative humidity
      (RH). At higher light intensity of 10.6 (W m(-2)), the HONO production rate
      increased to 2.1.10(10) molecules cm(-2) s(-1). A high NO2 to HONO conversion
      yield of up to 84% was observed. This result strongly suggests that a light
      driven process of indoor HONO production is operational. This work highlights the
      potential of paint surfaces to generate HONO within indoor environments by light
      induced NO2 heterogeneous reactions.

PMID- 24723353
TI  - Electrochemical advanced oxidation technologies for removal of organic pollutants
      from water.

PMID- 24723354
TI  - Physico-chemical characterisation of glass soiling in rural, urban and industrial
      environments.
AB  - Glass materials are broadly used in the built environment (windows, facades,
      roofs, museum showcases, and solar panels) due to their optical (transparency)
      and thermal properties. Their interaction with the multiphase atmospheric medium
      results in a more or less pronounced transparency loss called soiling. This
      phenomenon leads to a loss of amenity of artefacts; consequently, high cleaning
      costs have to be supported by public and private entities. Complete understanding
      of the nature of surface deposit appears thus extremely important for addressing
      strategies to control it. The present research is based on the sheltered
      exposure, in different environments, of durable glass panels during 1 year. At
      these different locations, airborne pollutant concentrations have also been
      monitored. Three environments have been investigated: rural (R), urban (U) and
      industrial (I). Results show that the mass of the deposit and the optical
      impairment of the glass (haze) are too spread to allow discriminating between
      different environments. However, the analyses of soluble species and particulate
      organic matter allow identifying factors responsible for soiling and highlighted
      the reactivity of deposit to relative humidity which favours post-deposit
      evolution. 

PMID- 24723355
TI  - Evaluate the heavy metal toxicity to Pseudomonas fluorescens in a low levels of
      metal-chelates minimal medium.
AB  - A 2-(n-morpholino)ethane sulfonic acid (MES)-buffered minimal medium with low
      levels of metal chelates was used to evaluate the heavy metal (Co+2, Pb+2, Zn+2,
      Fe+2, Fe+3, Cd+2, Cu+2, and Cr+6) toxicity to Pseudomonas fluorescens through
      minimizing the limitation of the existing medium. The interaction between
      bacteria and heavy metals was real-time monitored by microcalorimetry and
      reflected by thermogenic curves. Compared with the main parameters, microbial
      growth rate constant k and total heat evolution Q total, a general order of
      toxicity was found to be Fe+3<Co+2<Fe+2<Cu+2<Cr+6<Zn+2<Pb+2<Cd+2. The main metal
      speciation was Co+2, Zn+2, Fe+2, Cd+2, PbOH+, Fe(OH)+2, CuOH+, HCrO4-, and CrO4(
      2) at pH 6.4. These metal speciations are main factors to exhibit the metal
      toxicity to bacteria. To validate their interaction, the surface chemical
      functional groups of P. fluorescens biomass identified by Fourier transform
      infrared (FTIR) were amino, carboxyl, hydroxyl, and phosphoryl groups, which
      maybe involved in the biosorption of metal ions.

PMID- 24723356
TI  - Identifying gene-environment and gene-gene interactions using a progressive
      penalization approach.
AB  - In genomic studies, identifying important gene-environment and gene-gene
      interactions is a challenging problem. In this study, we adopt the statistical
      modeling approach, where interactions are represented by product terms in
      regression models. For the identification of important interactions, we adopt
      penalization, which has been used in many genomic studies. Straightforward
      application of penalization does not respect the "main effect, interaction"
      hierarchical structure. A few recently proposed methods respect this structure by
      applying constrained penalization. However, they demand very complicated
      computational algorithms and can only accommodate a small number of genomic
      measurements. We propose a computationally fast penalization method that can
      identify important gene-environment and gene-gene interactions and respect a
      strong hierarchical structure. The method takes a stagewise approach and
      progressively expands its optimization domain to account for possible
      hierarchical interactions. It is applicable to multiple data types and models. A
      coordinate descent method is utilized to produce the entire regularized solution
      path. Simulation study demonstrates the superior performance of the proposed
      method. We analyze a lung cancer prognosis study with gene expression
      measurements and identify important gene-environment interactions. 

PMID- 24723359
TI  - Effect of different irrigation protocols on the radicular dentin interface and
      bond strength with a metacrylate-based endodontic sealer.
AB  - This study assessed the influence of different endodontic chemical substances on
      the adhesion of the Epiphany SE/Resilon system (with and without resinous
      solvent) to radicular dentin walls, using the push-out test and scanning electron
      microscopy (SEM). Forty-eight root canals of human canines were prepared
      biomechanically with ProTaper rotary files (crown-down technique) and the
      radicular dentin was treated with either 17% EDTA, 2% chlorhexidine gel (CHX) or
      2.5% NaOCl (control). The root canals were filled with Resilon cones and Epiphany
      SE sealer with and without resinous solvent. Six groups of eight canals each had
      their roots sectioned transversally to obtain 1-mm thick slices. Data were
      subjected to statistical analysis by ANOVA and Tukey's tests. The specimens
      treated with 17% EDTA (1.59 +/- 0.91) presented higher bond strength (P < 0.05)
      than those treated with 2.5% NaOCl (0.93 +/- 0.27) and 2% CHX (0.92 +/- 0.22).
      Significantly higher bond strength (P < 0.05) was observed when the Epiphany SE
      was prepared with (1.37 +/- 0.78) than without (0.92 +/- 0.33) solvent. Adhesive
      failures were predominant in all groups. SEM analysis showed greater homogeneity
      of the filling mass when the solvent was added to the sealer. Treatment of root
      canal walls with 17% EDTA, and addition of a resinous solvent to Epiphany SE
      produced the highest adhesion to radicular dentin.

PMID- 24723360
TI  - Tissue phosphoproteomics with PolyMAC identifies potential therapeutic targets in
      a transgenic mouse model of HER2 positive breast cancer.
AB  - Altered protein phosphorylation is a feature of many human cancers that can be
      targeted therapeutically. Phosphopeptide enrichment is a critical step for
      maximizing the depth of phosphoproteome coverage by MS, but remains challenging
      for tissue specimens because of their high complexity. We describe the first
      analysis of a tissue phosphoproteome using polymer-based metal ion affinity
      capture (PolyMAC), a nanopolymer that has excellent yield and specificity for
      phosphopeptide enrichment, on a transgenic mouse model of HER2-driven breast
      cancer. By combining phosphotyrosine immunoprecipitation with PolyMAC, 411 unique
      peptides with 139 phosphotyrosine, 45 phosphoserine, and 29 phosphothreonine
      sites were identified from five LC-MS/MS runs. Combining reverse phase liquid
      chromatography fractionation at pH 8.0 with PolyMAC identified 1571 unique
      peptides with 1279 phosphoserine, 213 phosphothreonine, and 21 phosphotyrosine
      sites from eight LC-MS/MS runs. Linear motif analysis indicated that many of the
      phosphosites correspond to well-known phosphorylation motifs. Analysis of the
      tyrosine phosphoproteome with the Drug Gene Interaction database uncovered a
      network of potential therapeutic targets centered on Src family kinases with
      inhibitors that are either FDA-approved or in clinical development. These results
      demonstrate that PolyMAC is well suited for phosphoproteomic analysis of tissue
      specimens. 

PMID- 24723361
TI  - Fluorescent in situ hybridization of synaptic proteins imaged with super
      resolution STED microscopy.
AB  - Super-resolution fluorescence microscopy is still a developing field. One of the
      limitations has been that standard labeling assays, which had been developed for
      conventional imaging, must be adjusted and optimized for each super-resolution
      method. These methods are more sensitive to noise, and require more intense
      labeling than conventional microscopy, which is not always trivial to achieve.
      Here, we describe the use of stimulation-emission depletion (STED) microscopy to
      locate messenger RNAs (mRNAs) in single neurons with high spatial precision. We
      address several technical difficulties we encountered in using fluorescent in
      situ hybridization (FISH) for STED imaging. We optimized the experimental
      protocol to detect mRNAs and proteins simultaneously, by performing FISH and
      immunostaining on the same samples. We tested our imaging approach in primary
      hippocampal neurons, studying the mRNAs of three important presynaptic proteins
      (synaptobrevin, synaptotagmin, and synaptophysin). Our approach allowed us to
      relate changes in mRNA levels and localization to neuronal physiology, under
      different activity regimes and also during neuronal development. We conclude that
      FISH can be performed efficiently using super-resolution techniques. This should
      contribute significantly to the clarification of the molecular mechanisms that
      govern mRNA distribution and dynamics within cells.

PMID- 24723362
TI  - Unequivocal structural assignments of three cycloheptenoid intermediates for
      guaiane sesquiterpenes: an experimental and theoretical approach.

PMID- 24723363
TI  - IFN-gamma-producing NKT cells exacerbate sepsis by enhancing C5a generation via
      IL-10-mediated inhibition of CD55 expression on neutrophils.
AB  - A role for NKT cells has been implicated in sepsis, but the mechanism by which
      NKT cells contribute to sepsis remains unclear. Here, we examined WT and NKT-cell
      deficient mice of C57BL/6 background during cecal ligation and puncture-induced
      sepsis. The levels of C5a, IFN-gamma, and IL-10 were higher in the serum and
      peritoneal fluid of WT mice than in those of CD1d(-/-) mice, while the mortality
      rate was lower in CD1d(-/-) mice than in WT mice. C5a blockade decreased
      mortality of WT mice during sepsis, whereas it did not alter that of CD1d(-/-)
      mice. As assessed by intracellular staining, NKT cells expressed IFN-gamma, while
      neutrophils expressed IL-10. Upon coculture, IL-10-deficient NKT cells enhanced
      IL-10 production by WT, but not IFN-gammaR-deficient, neutrophils. Meanwhile,
      CD1d(-/-) mice exhibited high CD55 expression on neutrophils during sepsis,
      whereas those cells from WT mice expressed minimal levels of CD55. Recombinant IL
      10 administration into CD1d(-/-) mice reduced CD55 expression on neutrophils.
      Furthermore, adoptive transfer of sorted WT, but not IFN-gamma-deficient, NKT
      cells into CD1d(-/-) mice suppressed CD55 expression on neutrophils, but
      increased IL-10 and C5a levels. Taken together, IFN-gamma-producing NKT cells
      enhance C5a generation via IL-10-mediated inhibition of CD55 expression on
      neutrophils, thereby exacerbating sepsis. 

PMID- 24723364
TI  - Diversity study of 12 X-chromosomal STR loci in Hui ethnic from China.
AB  - X-chromosomal STRs (X-STRs) have been used as complements of autosomal STR
      application in recent years. In this work, we present population genetic data of
      12 X-STRs including DXS101, DXS10159, DXS10162, DXS10164, DXS6789, DXS7133,
      DXS7423, DXS7424, DXS8378, DXS981, GATA165B12, and GATA31E08 loci in a sample of
      231 unrelated healthy individuals from the Hui ethnic group in Ningxia Hui
      Autonomous Region, China. Allelic frequencies of the 12 X-STR loci and haplotypic
      frequencies of the reported linkage groups (DXS7424-DXS101 and DXS10159-DXS10164
      DXS10162) were investigated in the group, respectively. No STR loci showed
      significant deviations from the Hardy-Weinberg equilibriums and no linkage
      disequilibriums of pairwise loci were found after Bonferroni correction,
      respectively. A combined power of discrimination in female individuals was
      0.999999999985 and that in male individuals was 0.99999967, respectively. The
      combined mean exclusion chance in deficiency cases, normal trios and duo cases
      were 0.999934, 0.995754, and 0.999796, respectively. Significant differences were
      observed from 0 to 8 loci, when making comparisons between the data of Hui ethnic
      group and previously reported data from other 16 populations. The results
      indicated the new panel of 12 X-STR loci might be useful for forensic science
      application.

PMID- 24723365
TI  - Broadband WET: a novel technique for quantitative characterization of minor
      components in foods.
AB  - NMR analysis of foods frequently suffers from a problem of dynamic range, which
      limits the detection of minor components due to the huge signals of water and
      major components such as sugars. In the present study, we propose a new method
      named as 'broadband WET'. This pulse scheme was applied to persimmon fruit juice
      for saturating the resonances of water and sugars, which covered a broad
      bandwidth. In comparison with the conventional solvent suppression methods such
      as WET and DPFGSE-WATERGATE, it was shown that broadband WET provided highly
      selective suppression of resonances covering an extensive bandwidth and
      quantitative signals of minor components without distortion. The proposed method
      is suitable to detect quantitative signals of the minor components with a high
      sensitivity.

PMID- 24723366
TI  - DNA vaccines encoding membrane-bound or secreted forms of heat shock protein 70
      exhibit improved potency.
AB  - Traditional vaccine strategies are inefficient against challenge with complex
      pathogens including HIV; therefore, novel vaccine technologies are required. DNA
      vaccines are attractive as they are relatively cheap and easy to manufacture, but
      a major limitation has been their lack of immunogenicity in humans, which may be
      overcome with the incorporation of an adjuvant. HSP70 is a recognised damage
      associated molecular pattern, which is a potential adjuvant. We investigated the
      immunogenicity of a DNA vaccine encoding HIV gag and HSP70; the latter was
      genetically modified to produce cytoplasmic, secreted or membrane-bound HSP70,
      the expression of which was controlled by an independent promoter. The DNA was
      administered to C57BL/6 mice to evaluate gag-specific T-cell responses. Our
      results demonstrated the ability of membrane-bound and secreted HSP70 to
      significantly enhance gag-specific T-cell responses and increase the breadth of T
      cell responses to include subdominant epitopes. Membrane-bound or secreted HSP70
      also significantly improved the multifunctionality of HIV-specific T cells and T
      cell proliferation, which is important for maintaining T-cell integrity. Most
      importantly, the inclusion of membrane-bound HSP70, secreted HSP70 or a
      combination significantly increased protection in mice challenged with EcoHIV, a
      chimeric virus that replicates in mouse leukocytes in vivo. 

PMID- 24723368
TI  - 1H NMR for quantifying sulfide trapping efficiency by using 1,3,5-tris(2
      hydroxyethyl)-1,3,5-triazinane.
AB  - Hydrogen sulfide (H2S) is an extremely toxic colourless gas; it is corrosive and
      denser than air. It usually happens in oil and natural gas fields, refineries,
      coal mines, and in some industrial effluent treatment systems. This work presents
      an alternative method of monitoring and quantifying H2S trapping efficiency by
      using 1,3,5-tris(2-hydroxyethyl)-1,3,5-triazinane as a sequestering agent, and
      sodium sulfide as a source of sulfide ion, through (1)H NMR spectroscopy. The
      results proved that the reaction occurs very quickly at 20  degrees C at pH 7 and
      10. 3,5-di(2-hydroxyethyl)-1,3,5-thiodiazinane and 5-(2-hydroxyethyl)-1,3,5
      dithiozinane were observed and quantified; it was evidenced that (1)H NMR
      spectroscopy can be applied as a fast and effective method to quantify H2S
      trapping efficiency.

PMID- 24723367
TI  - Structure of vaccinia virus A46, an inhibitor of TLR4 signaling pathway, shows
      the conformation of VIPER motif.
AB  - Vaccinia virus (VACV) encodes many proteins that interfere with the host immune
      system. Vaccinia virus A46 protein specifically targets the BB-loop motif of TIR
      domain-containing proteins to disrupt receptor:adaptor (e.g., TLR4:MAL and
      TLR4:TRAM) interactions of the toll-like receptor signaling. The crystal
      structure of A46 (75-227) determined at 2.58 A resolution showed that A46 formed
      a homodimer and adopted a Bcl-2-like fold similar to other VACV proteins such as
      A52, B14, and K7. Our structure also revealed that VIPER (viral inhibitory
      peptide of TLR4) motif resides in the alpha1-helix and six residues of the VIPER
      region were exposed to surface for binding to target proteins. In vitro binding
      assays between wild type and six mutants A46 (75-227) and full-length MAL
      identified critical residues in the VIPER motif. Computational modeling of the
      A46:MAL complex structure showed that the VIPER region of A46 and AB loop of MAL
      protein formed a major binding interface. In summary, A46 is a homodimer with a
      Bcl-2-like fold and VIPER motif is believed to be involved in the interaction
      with MAL protein based on our binding assays.

PMID- 24723369
TI  - Multivariate optimization of a headspace solid-phase microextraction method
      followed by gas chromatography with mass spectrometry for the determination of
      terpenes in Nicotiana langsdorffii.
AB  - A simple and sensitive procedure based on headspace solid-phase microextraction
      and gas chromatography with mass spectrometry was developed for the determination
      of five terpenes (alpha-pinene, limonene, linalool, alpha-terpineol, and
      geraniol) in the leaves of Nicotiana langsdorffii. The microextraction conditions
      (extraction temperature, equilibration time, and extraction time) were optimized
      by means of a Doehlert design. The experimental design showed that, for alpha
      pinene and limonene, a low temperature and a long extraction time were needed for
      optimal extraction, while linalool, alpha-terpineol, and geraniol required a high
      temperature and a long extraction time. The chosen compromise conditions were
      temperature 60 degrees C, equilibration time 15 min and extraction time 50 min.
      The main analytical figures of the optimized method were evaluated; LODs ranged
      from 0.07 ng/g (alpha-pinene) to 8.0 ng/g (geraniol), while intraday and interday
      repeatability were in the range 10-17% and 9-13%, respectively. Finally, the
      procedure was applied to in vitro wild-type and transgenic specimens of N.
      langsdorffii subjected to abiotic stresses (chemical and heat stress). With the
      exception of geraniol (75-374 ng/g), low concentration levels of terpenes were
      measured (ng/g level or lower); some interesting variations in terpene
      concentration induced by abiotic stress were observed. 

PMID- 24723370
TI  - Microglia of medicinal leech (Hirudo medicinalis) express a specific activation
      marker homologous to vertebrate ionized calcium-binding adapter molecule 1
      (Iba1/alias aif-1).
AB  - The Ionized calcium-Binding Adapter molecule 1 (Iba1), also known as Allograft
      Inflammatory Factor 1 (AIF-1), is a 17 kDa cytokine-inducible protein, produced
      by activated macrophages during chronic transplant rejection and inflammatory
      reactions in Vertebrates. In mammalian central nervous system (CNS), Iba1 is a
      sensitive marker associated with activated macrophages/microglia and is
      upregulated following neuronal death or brain lesions. The medicinal leech Hirudo
      medicinalis is able to regenerate its CNS after injury, leading to a complete
      functional repair. Similar to Vertebrates, leech neuroinflammatory processes are
      linked to microglia activation and recruitment at the lesion site. We identified
      a gene, named Hmiba1, coding a 17.8 kDa protein showing high similarity with
      Vertebrate AIF-1. The present work constitutes the first report on an Iba1
      protein in the nervous system of an invertebrate. Immunochemistry and gene
      expression analyses showed that HmIba1, like its mammalian counterpart, is
      modulated in leech CNS by mechanical injury or chemical stimuli (ATP). We
      presently demonstrate that most of leech microglial cells migrating and
      accumulating at the lesion site specifically expressed the activation marker
      HmIba1. While the functional role of Iba1, whatever species, is still unclear in
      reactive microglia, this molecule appeared as a good selective marker of
      activated cells in leech and presents an interesting tool to investigate the
      functions of these cells during nerve repair events.

PMID- 24723371
TI  - CTLA-4 (CD152) enhances the Tc17 differentiation program.
AB  - Although CD8(+) T cells that produce IL-17 (Tc17 cells) have been linked to host
      defense, Tc17 cells show reduced cytotoxic activity, which is the characteristic
      function of CD8(+) T cells. Here, we show that CTLA-4 enhances the frequency of
      IL-17 in CD8(+) T cells, indicating that CTLA-4 (CD152) specifically promotes
      Tc17 differentiation. Simultaneous stimulation of CTLA-4(+/+) and CTLA-4(-/-) T
      cells in cocultures and agonistic CTLA-4 stimulation unambiguously revealed a
      cell-intrinsic mechanism for IL-17 control by CTLA-4. The quality of CTLA-4
      induced Tc17 cells was tested in vivo, utilizing infection with the facultative
      intracellular bacterium Listeria monocytogenes (LM). Unlike CTLA-4(+/+) Tc17
      cells, CTLA-4(-/-) were nearly as efficient as Tc1 CTLA-4(+/+) cells in LM
      clearance. Additionally, adoptively transferred CTLA-4(-/-) Tc17 cells expressed
      granzyme B after rechallenge, and produced Tc1 cytokines such as IFN-gamma and
      TNF-alpha, which strongly correlate with bacterial clearance. CTLA-4(+/+) Tc17
      cells demonstrated a high-quality Tc17 differentiation program ex vivo, which was
      also evident in isolated IL-17-secreting Tc17 cells, with CTLA-4-mediated
      enhanced upregulation of Tc17-related molecules such as IL-17A, RORgammat, and
      IRF-4. Our results show that CTLA-4 promotes Tc17 differentiation that results in
      robust Tc17 responses. Its inactivation might therefore represent a central
      therapeutic target to enhance clearance of infection. 

PMID- 24723372
TI  - Role of connecting loop I in catalysis and allosteric regulation of human
      glucokinase.
AB  - Glucokinase (GCK, hexokinase IV) is a monomeric enzyme with a single glucose
      binding site that displays steady-state kinetic cooperativity, a functional
      characteristic that affords allosteric regulation of GCK activity. Structural
      evidence suggests that connecting loop I, comprised of residues 47-71,
      facilitates cooperativity by dictating the rate and scope of motions between the
      large and small domains of GCK. Here we investigate the impact of varying the
      length and amino acid sequence of connecting loop I upon GCK cooperativity. We
      find that sequential, single amino acid deletions from the C-terminus of
      connecting loop I cause systematic decreases in cooperativity. Deleting up to two
      loop residues leaves the kcat value unchanged; however, removing three or more
      residues reduces kcat by 1000-fold. In contrast, the glucose K0.5 and KD values
      are unaffected by shortening the connecting loop by up to six residues.
      Substituting alanine or glycine for proline-66, which adopts a cis conformation
      in some GCK crystal structures, does not alter cooperativity, indicating that
      cis/trans isomerization of this loop residue does not govern slow conformational
      reorganizations linked to hysteresis. Replacing connecting loop I with the
      corresponding loop sequence from the catalytic domain of the noncooperative
      isozyme human hexokinase I (HK-I) eliminates cooperativity without impacting the
      kcat and glucose K0.5 values. Our results indicate that catalytic turnover
      requires a minimal length of connecting loop I, whereas the loop has little
      impact upon the binding affinity of GCK for glucose. We propose a model in which
      the primary structure of connecting loop I affects cooperativity by influencing
      conformational dynamics, without altering the equilibrium distribution of GCK
      conformations.

PMID- 24723373
TI  - Identification and analysis of alkaloids in cortex Phellodendron amurense by high
      performance liquid chromatography with electrospray ionization mass spectrometry
      coupled with photodiode array detection.
AB  - Alkaloids from Cortex Phellodendron amurense Rupr. were identified to determine
      the material basis for the bioactivity of this herb. HPLC-ESI-MS with photodiode
      array detection coupled to XCharge C18 column was applied to analyze the
      alkaloids qualitatively and quantitatively. A total of 37 alkaloids were
      identified and tentatively characterized from the ethanol extract by online ESI
      MS(n) fragmentation and UV spectral analysis. A total of ten alkaloids, including
      four novel natural products, were tentatively identified for the first time in P.
      amurense. The fragmentation pathways for certain compounds were analyzed. The
      contents of a pair of isomers (columbamine and jatrorrhizine) and four main
      alkaloids (phellodendrine, magnoflorine, berberine, and palmatine) were
      simultaneously quantified using the aforementioned method. Results showed that
      the newly discovered and known components of P. amurense were helpful in
      determining the material basis for the bioactivity of the herb. The application
      of the XCharge C18 column is a suitable and practical method for the isolation of
      alkaloids in plants. 

PMID- 24723375
TI  - Optimal administrative scale for planning public services: a social cost model
      applied to Flemish hospital care.
AB  - In choosing the scale of public services, such as hospitals, both economic and
      public administrative considerations play important roles. The scale and the
      corresponding spatial distribution of public institutions have consequences for
      social costs, defined as the institutions' operating costs and the users' travel
      costs (which include the money and time costs). Insight into the relationship
      between scale and spatial distribution and social costs provides a practical
      guide for the best possible administrative planning level. This article presents
      a purely economic model that is suitable for deriving the optimal scale for
      public services. The model also reveals the corresponding optimal administrative
      planning level from an economic perspective. We applied this model to hospital
      care in Flanders for three different types of care. For its application, we
      examined the social costs of hospital services at different levels of
      administrative planning. The outcomes show that the social costs of
      rehabilitation in Flanders with planning at the urban level (38 areas) are 11%
      higher than those at the provincial level (five provinces). At the regional level
      (18 areas), the social costs of rehabilitation are virtually equal to those at
      the provincial level. For radiotherapy, there is a difference of 88% in the
      social costs between the urban and the provincial level. For general care, there
      are hardly any cost differences between the three administrative levels. Thus,
      purely from the perspective of social costs, rehabilitation should preferably be
      planned at the regional level, general services at the urban level and
      radiotherapy at the provincial level.

PMID- 24723374
TI  - General flexible nature of the cytosolic regions of fungal transient receptor
      potential (TRP) channels, revealed by expression screening using GFP-fusion
      techniques.
AB  - Transient receptor potential (TRP) channels are members of the voltage gated ion
      channel superfamily and display the unique characteristic of activation by
      diverse stimuli. We performed an expression analysis of fungal TRP channels,
      which possess relatively simple structures yet share the common functional
      characteristics with the other members, using a green fluorescent protein-based
      screening methodology. The analysis revealed that all the tested fungal TRP
      channels were severely digested in their cytosolic regions during expression,
      implying the common flexibility of this region, as observed in the recent
      structural analyses of the fungal member, TRPGz. These characteristics are likely
      to be important for their diverse functions.

PMID- 24723376
TI  - Inhibition of cell proliferation in black-capped chickadees suggests a role for
      neurogenesis in spatial learning.
AB  - Following development, the avian brain continues to produce neurons throughout
      adulthood, which functionally integrate throughout the telencephalon, including
      the hippocampus. In food-storing birds like the black-capped chickadee (Poecile
      atricapillus), new neurons incorporated into the hippocampus are hypothesized to
      play a role in spatial learning. Previous results on the relation between
      hippocampal neurogenesis and spatial learning, however, are correlational. In
      this study, we experimentally suppressed hippocampal neuronal recruitment and
      tested for subsequent effects on spatial learning in adult chickadees. After
      chickadees exhibited significant learning, we treated birds with daily injections
      of either saline or methylazoxymethanol (MAM), a toxin that suppresses cell
      proliferation in the brain and monitored subsequent spatial learning. MAM
      treatment significantly reduced cell proliferation around the lateral ventricles
      and neuronal recruitment in the hippocampus, measured using the cell birth marker
      bromodeoxyuridine. MAM-treated birds performed significantly worse than controls
      on the spatial learning task 12 days following the initiation of MAM treatment, a
      time when new neurons would begin functionally integrating into the hippocampus.
      This difference in learning, however, was limited to a single trial. MAM
      treatment did not affect any measure of body condition, suggesting learning
      impairments were not a product of non-specific adverse effects of MAM. This is
      the first evidence of a potential causal link between hippocampal neurogenesis
      and spatial learning in birds.

PMID- 24723378
TI  - Minimization of carryover for high-throughput liquid chromatography with tandem
      mass spectrometry analysis of 14 mycotoxins in corn grits.
AB  - A method for the simultaneous analysis of 14 mycotoxins with the minimization of
      carryover was developed. Our verification experiments suggested that the
      carryover occurred due to the chelation of fumonisins with the metal. To wash the
      fumonisins from the metal, the inner surface of the injection needle was rinsed
      with 10 mM trisodium citrate and 1% formic acid in
      water/methanol/acetonitrile/isopropanol after each injection, and the analysis
      was performed on a metal-free Mastro C18 column. This approach remarkably
      minimized the carryover of fumonisins. Fourteen mycotoxins in samples were
      extracted with 2% acetic acid in water/acetonitrile and a quick, easy, cheap,
      effective, rugged, and safe extraction kit, purified on a MultiSep 229 Ochra, and
      then quantified by liquid chromatography with tandem mass spectrometry.
      Determinations performed using this method produced a linearity greater than 0.99
      and recoveries ranging from 72.6 to 117.4%, with good intraday precision from 4.0
      to 12.4%, and interday precision from 6.5 to 17.0%. The limits of detection
      ranged from 0.01 to 0.71 MUg/kg, demonstrating that a highly sensitive method for
      the simultaneous analysis of mycotoxins over a wide range of concentrations was
      achieved with minimal carryover. When 12 samples of commercially available corn
      grits were analyzed with this method, deoxynivalenol, fumonisin B1, fumonisin B2,
      fumonisin B3, and zearalenone were present most frequently. 

PMID- 24723377
TI  - A novel T-cell receptor mimic defines dendritic cells that present an
      immunodominant West Nile virus epitope in mice.
AB  - We used a newly generated T-cell receptor mimic monoclonal antibody (TCRm MAb)
      that recognizes a known nonself immunodominant peptide epitope from West Nile
      virus (WNV) NS4B protein to investigate epitope presentation after virus
      infection in C57BL/6 mice. Previous studies suggested that peptides of different
      length, either SSVWNATTAI (10-mer) or SSVWNATTA (9-mer) in complex with class I
      MHC antigen H-2D(b) , were immunodominant after WNV infection. Our data establish
      that both peptides are presented on the cell surface after WNV infection and that
      CD8(+) T cells can detect 10- and 9-mer length variants similarly. This result
      varies from the idea that a given T-cell receptor (TCR) prefers a single peptide
      length bound to its cognate class I MHC. In separate WNV infection studies with
      the TCRm MAb, we show that in vivo the 10-mer was presented on the surface of
      uninfected and infected CD8alpha(+) CD11c(+) dendritic cells, which suggests the
      use of direct and cross-presentation pathways. In contrast, CD11b(+) CD11c(-)
      cells bound the TCRm MAb only when they were infected. Our study demonstrates
      that TCR recognition of peptides is not limited to certain peptide lengths and
      that TCRm MAbs can be used to dissect the cell-type specific mechanisms of
      antigen presentation in vivo. 

PMID- 24723379
TI  - Abnormalities in iNKT cells are associated with impaired ability of monocytes to
      produce IL-10 and suppress T-cell proliferation in sarcoidosis.
AB  - Sarcoidosis is a multisystem granulomatous disorder characterized by marked T
      cell expansion of T helper 1 (Th1) cells. The cause of T-cell overactivity is
      unknown. We hypothesized that interleukin-10 (IL-10) production by a yet
      undefined cell type might be defective, resulting in loss of regulation of T-cell
      activity. Focusing on IL-10-producing monocytes, we first showed that monocytes
      isolated from the peripheral blood of corticosteroid-naive sarcoidosis patients
      (n = 51) produced less IL-10 compared to controls, and were less able to suppress
      T-cell proliferation. In addition, monocytic IL-10 production correlated
      negatively with disease activity score. As invariant natural killer T (iNKT)
      cells are known to both interact with monocytes and be reduced in sarcoidosis
      patients, we then asked whether iNKT-specific defects might be responsible for
      this reduced IL-10 production. We found that greater numbers of circulating iNKT
      cells was associated with higher IL-10 production. Moreover, iNKT cells enhanced
      monocytic IL-10 production in vitro. Defective IL-10 production and T-cell
      suppression by sarcoidosis monocytes could be restored following their coculture
      with iNKT cells, in a CD1d- and cell contact-dependent process. We suggest that
      reduced iNKT-cell numbers in sarcoidosis may lead to impaired monocytic IL-10
      production and unchecked T-cell expansion in sarcoidosis. These findings provide
      fresh insight into the mechanism of sarcoidosis disease, and interaction between
      iNKT cells and monocytes. 

PMID- 24723380
TI  - Optimization of the enantioseparation of a diaryl-pyrazole sulfonamide derivative
      by capillary electrophoresis in a dual CD mode using experimental design.
AB  - A CE method using dual cationic and neutral cyclodextrins (CD) was optimized for
      the enantiomeric separation of a compound presenting a diaryl sulfonamide group.
      Preliminary studies were made to select the optimal CDs and pH of the BGE. Two
      CDs (amino-beta-CD and beta-CD) were selected to separate the enantiomers in a 67
      mM phosphate buffer at pH 7.4. However, the repeatability of the analyses
      obtained on bare-fused silica capillary was not acceptable owing to the
      adsorption of the amino-beta-CD to the capillary. To prevent this, a dynamic
      coating of the capillary was used employing five layers of ionic-polymer
      (poly(diallyldimethylammonium) chloride (PDADMAC) and poly(sodium 4
      styrenesulfonate). The efficiency of the coating was assessed by measuring the
      EOF stability. Repeatability of the injections was obtained when intermediate
      coating with PDADMAC was performed between each run. Secondly, this
      enantioseparation method was optimized using a central composite circumscribed
      design including three factors: amino-beta-CD and beta-CD concentrations and the
      percentage of methanol. Under the optimal conditions (i.e. 16.6 mM of amino-beta
      CD, 2.6 mM of beta-CD, 0% MeOH in 67 mM phosphate buffer (pH 7.4) as BGE,
      cathodic injection 0.5 psi, 5 s, separation voltage 15 kV and a temperature of 15
      degrees C), complete enantioresolution of the analyte was obtained. It is worth
      mentioning that the design of experiments (DOE) protocol employed showed a
      significant interaction between CDs, highlighting the utility of DOE in method
      development. Finally, small variations in the ionic-polymer concentrations did
      not significantly influence the EOF, confirming the robustness of the coating
      method. 

PMID- 24723381
TI  - Low serum thyrotropin level and duration of suppression as a predictor of major
      osteoporotic fractures-the OPENTHYRO register cohort.
AB  - The relationship between thyrotoxicosis and osteoporotic fractures remains
      controversial, particularly in men. Register-based cohort study including all
      patients with a serum thyrotropin (TSH) measurement in the region of Funen 1996
      2010. All TSH determinations were done in the same lab, which served all
      hospitals and General Practice (GP) practices in the region. Persons with raised
      TSH or a history of thyroid/pituitary disease or use of thyroid medications were
      excluded. The study population consisted of 222,138 (96%) persons with normal and
      9217 (4%) with low TSH (<0.3 mIU/L). A single low TSH at baseline was associated
      with increased risk of hip fractures (adj HR 1.16, 95% CI 1.07-1.26, p < 0.001)
      but not major osteoporotic fractures (MOF, adj HR 1.06, 95% CI 0.99-1.12, p =
      0.058) over a median follow-up of 7.5 years. When men were analyzed separately,
      results did not reach statistical significance. We found a significant
      association between duration of thyrotoxicosis and fracture. For each 6 months in
      which the mean TSH value was decreased (<0.3 mIU/L), hip fracture risk increased
      by a factor 1.07 (adj HR, 95% CI 1.04-1.10, p < 0.001) and MOF by 1.05 (adj HR,
      95% CI 1.03-1.07, p < 0.001). Overt thyrotoxicosis was associated with an
      increased risk of hip fractures but not MOF. In euthyroid patients, the risk of
      fractures increased significantly with each SD unit of TSH decrease: Hip fracture
      (HR 1.45, 95% CI 1.22-1.71, p < 0.001) and MOF (HR 1.32, 95% CI 1.19-1.46, p <
      0.001). In a population-based cohort, a single, first measurement of decreased
      TSH in patients without known thyroid disease was associated with an increased
      long-term risk of hip fracture, which remained significant in women but not in
      men after adjusting for confounders. Moreover, the risk of both hip fracture and
      MOF increased exponentially by the length of time during which TSH had remained
      low.

PMID- 24723382
TI  - Active site conformational changes upon reaction intermediate biotinyl-5'-AMP
      binding in biotin protein ligase from Mycobacterium tuberculosis.
AB  - Protein biotinylation, a rare form of post-translational modification, is found
      in enzymes required for lipid biosynthesis. In mycobacteria, this process is
      essential for the formation of their complex and distinct cell wall and has
      become a focal point of drug discovery approaches. The enzyme responsible for
      this process, biotin protein ligase, substantially varies in different species in
      terms of overall structural organization, regulation of function and substrate
      specificity. To advance the understanding of the molecular mechanism of
      biotinylation in Mycobacterium tuberculosis we have biochemically and
      structurally characterized the corresponding enzyme. We report the high
      resolution crystal structures of the apo-form and reaction intermediate biotinyl
      5'-AMP-bound form of M. tuberculosis biotin protein ligase. Binding of the
      reaction intermediate leads to clear disorder-to-order transitions. We show that
      a conserved lysine, Lys138, in the active site is essential for biotinylation.

PMID- 24723383
TI  - Molecular testing in lung cancer: fine-needle aspiration specimen adequacy and
      test prioritization prior to the CAP/IASLC/AMP Molecular Testing Guideline
      publication.
AB  - BACKGROUND: Subtyping of lung carcinoma with immunohistochemistry is essential
      for diagnosis, whereas molecular testing (MT) is required for therapy guidance.
      In the current study, the authors report on MT performed on fine-needle
      aspiration specimens at the study institution over a 2-year period preceding the
      April 2013 College of American Pathologists (CAP)/International Association for
      the Study of Lung Cancer (IASLC)/Association for Molecular Pathology (AMP)
      Molecular Testing Guideline (MTG) publication. METHODS: The database of the study
      institution was retrospectively queried for cases of lung and thoracic/lower
      cervical lymph node fine-needle aspiration specimens for 2011 through 2012.
      RESULTS: Of 246 selected cases, 26 featured a limited amount of material in cell
      blocks. MT increased significantly between 2011 and 2012 and was requested in
      39.4% of cases (97 of 246 cases): 86 of those cases had at least 1 MT result and
      11 had insufficient material for any MT. Anaplastic lymphoma kinase (ALK) testing
      was performed in 9 cases in which DNA was insufficient for epidermal growth
      factor receptor (EGFR) testing. In addition, 13 cases of adenocarcinoma/non-small
      cell lung carcinoma had at least 1 MT canceled because of insufficient DNA, but
      at the same time had an average of 3.46 immunohistochemical stains performed.
      CONCLUSIONS: Of all the cytology specimens, 10.6% featured limited material;
      however, no universally accepted testing sequence priority was available at the
      time the study was performed. As per the MTG, MT should take precedence over
      immunohistochemistry in cases of adenocarcinoma/non-small cell lung carcinoma.
      Approximately 5.3% of the specimens in the current study had insufficient
      material for MT while having multiple stains performed instead. The MTG also
      recommend performing EGFR before ALK testing; the authors found 9 cases with
      insufficient material for EGFR testing that had ALK testing performed. The
      results of the current study underscore the need for a testing prioritization
      algorithm in view of the MTG publication to serve as reference for both
      clinicians and pathologists.

PMID- 24723384
TI  - Cationic isotachophoresis separation of the biomarker cardiac troponin I from a
      high-abundance contaminant, serum albumin.
AB  - Cationic ITP was used to separate and concentrate fluorescently tagged cardiac
      troponin I (cTnI) from two proteins with similar isoelectric properties in a PMMA
      straight-channel microfluidic chip. In an initial set of experiments, cTnI was
      effectively separated from R-Phycoerythrin using cationic ITP in a pH 8 buffer
      system. Then, a second set of experiments was conducted in which cTnI was
      separated from a serum contaminant, albumin. Each experiment took ~10 min or less
      at low electric field strengths (34 V/cm) and demonstrated that cationic ITP
      could be used as an on-chip removal technique to isolate cTnI from albumin. In
      addition to the experimental work, a 1D numerical simulation of our cationic ITP
      experiments has been included to qualitatively validate experimental
      observations.

PMID- 24723385
TI  - Advances in cellular and tissue engineering using layer-by-layer assembly.
AB  - Layer-by-layer (LbL) assembly is a self-assembly technique used to develop
      multilayer films based on complementary interactions between film components.
      These multilayer films have had a significant impact on the fields of cellular
      and tissue engineering. The aim of cellular engineering is to understand and
      control cell behavior, which not only impacts applications in regenerative
      medicine but also other biomedical therapies that rely on cell interactions with
      biomaterials, including treatments for autoimmune disorders and cancer. Tissue
      engineering approaches to tissue repair and regeneration utilize three
      dimensional biomaterial scaffolds that interact favorably with cells. Cellular
      engineering studies can better inform the design of these scaffolds. The ease of
      tuning the chemical and mechanical properties of LbL films, the ability to coat a
      variety of medically relevant substrates (including cell culture surfaces and
      scaffolds), and the wide range of species that can be incorporated into these
      films (ranging from proteins to small molecules) have led to the successful use
      of LbL assembly for a variety of cellular and tissue engineering applications.
      The films used in these biomedical applications can be divided into those that
      release therapeutics, often with controlled stimuli-responsive release behavior,
      and those that act without releasing these agents.

PMID- 24723386
TI  - Inflammatory markers and risk of hip fracture in older white women: the study of
      osteoporotic fractures.
AB  - Hip fractures are the most devastating consequence of osteoporosis and impact 1
      in 6 white women leading to a two- to threefold increased mortality risk in the
      first year. Despite evidence of inflammatory markers in the pathogenesis of
      osteoporosis, few studies have examined their effect on hip fracture. To
      determine if high levels of inflammation increase hip fracture risk and to
      explore mediation pathways, a case-cohort design nested in a cohort of 4709 white
      women from the Study of Osteoporotic Fractures was used. A random sample of 1171
      women was selected as the subcohort (mean age 80.1 +/- 4.2 years) plus the first
      300 women with incident hip fracture. Inflammatory markers interleukin-6 (IL-6)
      and soluble receptors (SR) for IL-6 (IL-6 SR) and tumor necrosis factor (TNF SR1
      and TNF SR2) were measured, and participants were followed for a median
      (interquartile range) of 6.3 (3.7, 6.9) years. In multivariable models, the
      hazard ratio (HR) of hip fracture for women in the highest inflammatory marker
      level (quartile 4) was 1.64 (95% confidence interval [CI], 1.09-2.48, p trend =
      0.03) for IL-6 and 2.05 (95% CI, 1.35-3.12, p trend <0.01) for TNF SR1 when
      compared with women in the lowest level (quartile 1). Among women with 2 and 3-4
      inflammatory markers in the highest quartile, the HR of hip fracture was 1.51
      (95% CI, 1.07-2.14) and 1.42 (95% CI, 0.87-2.31) compared with women with zero to
      one marker(s) in the highest quartile (p trend = 0.03). After individually
      adjusting for seven potential mediators, cystatin-C (a biomarker of renal
      function) and bone mineral density (BMD) attenuated HRs among women with the
      highest inflammatory burden by 64% and 50%, respectively, suggesting a potential
      mediating role. Older white women with high inflammatory burden are at increased
      risk of hip fracture in part due to poor renal function and low BMD.

PMID- 24723387
TI  - Vaccine for human contraception targeting sperm Izumo protein and YLP12 dodecamer
      peptide.
AB  - There is an urgent need to develop a better method of contraception which is non
      steroidal and reversible to control world population explosion and unintended
      pregnancies. Contraceptive vaccines (CV), especially targeting sperm-specific
      proteins, can provide an ideal contraceptive modality. Sperm-specific proteins
      can induce an immune response in women as well as men, thus can be used for CV
      development in both sexes. In this article, we will review two sperm-specific
      proteins, namely Izumo protein and YLP12 dodecamer peptide. Gene-knockout studies
      indicate that Izumo protein is essential for sperm-egg membrane fusion.
      Vaccination with Izumo protein or its cDNA causes a significant reduction in
      fertility of female mice. The antibodies to human Izumo inhibit human sperm
      penetration assay. Recently, our laboratory found that a significant percentage
      of infertile women have antibodies to Izumo protein. The second sperm-specific
      protein is YLP12 , a peptide mimetic sequence present on human sperm involved in
      recognition and binding to the human oocyte zona pellucida. Vaccination with
      YLP12 or its cDNA causes long-term, reversible contraception, without side
      effects, in female mice. Infertile, but not fertile, men and women have
      antibodies to YLP12 peptide. Our laboratory has isolated, cloned, and sequenced
      cDNA encoding human single chain variable fragment (scFv) antibody from infertile
      men which reacts with YLP12 peptide. The human YLP12 scFv antibody may provide a
      novel passive immunocontraceptive, the first of its kind. In conclusion, sperm
      specific Izumo protein and YLP12 peptide can provide exciting candidates for
      antisperm CV development.

PMID- 24723388
TI  - Preparative isolation and analysis of alcohol dehydrogenase inhibitors from
      Glycyrrhiza uralensis root using ultrafiltration combined with high-performance
      liquid chromatography and high-speed countercurrent chromatography.
AB  - A simple, rapid, and effective assay based on ultrafiltration combined with high
      performance liquid chromatography and high-speed countercurrent chromatography
      was developed for screening and purifying alcohol dehydrogenase inhibitors from
      Glycyrrhiza uralensis root extract. Experiments were carried out to optimize
      binding conditions including alcohol dehydrogenase concentration, incubation
      time, temperature, and pH. By comparing the chromatograms, three compounds were
      found possessing alcohol dehydrogenase binding activity in Glycyrrhiza uralensis
      root. Under the target-guidance of ultrafiltration combined with the high
      performance liquid chromatography experiment, liquiritin (1), isoliquiritin (2),
      and liquiritigenin (3) were separated by high-speed countercurrent chromatography
      using ethyl acetate/methanol/water (5:1:4) as the solvent system. The alcohol
      dehydrogenase inhibitory activities of these three isolated compounds were
      assessed; compound 2 showed strongest inhibitory activity with an IC50 of 8.95
      MUM. The results of the present study indicated that the combinative method using
      ultrafiltration, high-performance liquid chromatography and high-speed
      countercurrent chromatography could be widely applied for the rapid screening and
      isolation of enzyme inhibitors from complex mixtures. 

PMID- 24723389
TI  - Tetraspanins CD9 and CD151 at the immune synapse support T-cell integrin
      signaling.
AB  - Understanding how the immune response is activated and amplified requires
      detailed knowledge of the stages in the formation of the immunological synapse
      (IS) between T lymphocytes and antigen-presenting cells (APCs). We show that
      tetraspanins CD9 and CD151 congregate at the T-cell side of the IS. Silencing of
      CD9 or CD151 blunts the IL-2 secretion and expression of the activation marker
      CD69 by APC-conjugated T lymphocytes, but does not affect the accumulation of CD3
      or actin to the IS, or the translocation of the microtubule-organizing center
      toward the T-B contact area. CD9 or CD151 silencing diminishes the relocalization
      of alpha4beta1 integrin to the IS and reduces the accumulation of high-affinity
      beta1 integrins at the cell-cell contact. These changes are accompanied by
      diminished phosphorylation of the integrin downstream targets FAK and ERK1/2. Our
      results suggest that CD9 and CD151 support integrin-mediated signaling at the IS.

PMID- 24723391
TI  - Determination of polar organic compounds in atmospheric aerosols by gas
      chromatography with ion trap tandem mass spectrometry.
AB  - A gas chromatography with ion trap mass spectrometry method has been developed
      and validated for the analysis of 27 polar organic compounds in atmospheric
      aerosols. The target analytes were low-molecular-weight carboxylic acids and
      methoxyphenols, as relevant markers of source emissions and photochemical
      processes of organic aerosols. The operative parameters were optimized in order
      to achieve the best sensitivity and selectivity for the analysis. In comparison
      with the previous gas chromatography with mass spectrometry procedure based on
      single ion monitoring detection, the tandem mass spectrometry technique increased
      the analytical sensitivity by reducing detection limits for standard solutions
      from 1-2.6 to 0.1-0.4 ng/MUL ranges (concentrations in the injected solution). In
      addition, it enhanced selectivity by reducing matrix interferences and chemical
      noise in the chromatogram. The applicability of the developed method in air
      quality monitoring campaigns was effectively checked by analyzing environmental
      samples collected in the Po Valley (Northern Italy) in different seasons. The
      obtained results indicate that the ion trap mass spectrometer may be an ideal
      alternative to high-resolution mass spectrometers for the user-friendly and cost
      effective determination of a wide range of molecular tracers in airborne
      particulate matter. 

PMID- 24723392
TI  - Differential presentation of endogenous and exogenous hepatitis B surface
      antigens influences priming of CD8(+) T cells in an epitope-specific manner.
AB  - Little is known about whether presentation of endogenous and exogenous hepatitis
      B virus (HBV) surface antigens on APCs targeted by vaccination and/or virus
      harboring hepatocytes influences de novo priming of CD8(+) T cells. We showed
      that surface antigen-expressing transfectants exclusively display a K(b) /S190
      epitope, whereas cells pulsed with recombinant surface particles (rSPs)
      exclusively present a K(b) /S208 epitope to CD8(+) T cells. The differential
      presentation of these epitopes largely reflects the selective, but not exclusive,
      priming of K(b) /S190- and K(b) /S208-specific T cells in C57BL/6 mice by
      endogenous/DNA- or exogenous/protein-based vaccines, respectively. Silencing the
      K(b) /S190 epitope (K(b) /S190V194F ) in antigen-expressing vectors rescued the
      presentation of the K(b) /S208 epitope in stable transfectants and significantly
      enhanced priming of K(b) /S208-specific T cells in C57BL/6 mice. A K(b) /S190
      mediated immunodominance operating in surface antigen-expressing cells, but not
      in rSP-pulsed cells, led to an efficient suppression in the presentation of the
      K(b) /S208 epitope and a consequent decrease in the priming of K(b) /S208
      specific T cells. This K(b) /S190-mediated immunodominance also operated in
      1.4HBV-S(mut) transgenic (tg) hepatocytes selectively expressing endogenous
      surface antigens and allowed priming of K(b) /S208- but not K(b) /S190-specific T
      cells in 1.4HBV-S(mut) tg mice. However, IFN-gamma(+) K(b) /S208-specific T cells
      could not inhibit HBV replication in the liver of 1.4HBV-S(mut) tg mice. These
      results have practical implications for the design of T-cell-stimulating
      therapeutic vaccines.

PMID- 24723393
TI  - Birth weight is not associated with risk of fracture: results from two Swedish
      cohort studies.
AB  - Development and growth in utero has been suggested to influence bone health.
      However, the relationship with risk of fracture in old age is largely unknown.
      Using Cox proportional hazards regression, we studied the association between
      birth weight and fractures at ages 50-94 among 10,893 men and women (48% women)
      from the Uppsala Birth Cohort Study (UBCoS, born 1915-29) and 1334 men from the
      Uppsala Longitudinal Study of Adult Men (ULSAM, born 1920-24). Measured birth
      weight was collected from hospital or midwives' records and fractures from the
      Swedish National Patient Register. We observed 2796 fractures (717 of these were
      hip fractures) in UBCoS and 335 fractures (102 hip fractures) in ULSAM. In UBCoS,
      the hazard ratio (HR) per 1 kg increase in birth weight, adjusted for sex and
      socioeconomic status at birth, was 1.01 [95% confidence interval (CI), 0.94-1.09]
      for any fracture and 1.06 (95% CI, 0.91-1.23) for hip fracture. Estimates in
      ULSAM were similar. We did not observe a differential association of birth weight
      with fractures occurring before age 70 or after age 70 years. Neither birth
      weight standardized for gestational age nor gestational duration was associated
      with fracture rate. In linear regression, birth weight was not associated with
      bone mineral density among 303 men who were 82-years-old in ULSAM but showed
      positive associations with total body bone mineral content (beta per kg increase
      in birth weight, adjusted for social class and age, 133; 95% CI, 30-227). This
      association was attenuated after further adjustment for body mass index and
      height (beta, 41; 95% CI, -43-126). We conclude that birth weight is associated
      with bone mineral content but this association does not translate into an
      association with risk of fracture in men and women aged 50-94 years.

PMID- 24723394
TI  - Polyamines cause plasma membrane depolarization, activate Ca2+-, and modulate H+
      ATPase pump activity in pea roots.
AB  - Polyamines regulate a variety of cation and K(+) channels, but their potential
      effects on cation-transporting ATPases are underexplored. In this work,
      noninvasive microelectrode ion flux estimation and conventional microelectrode
      techniques were applied to study the effects of polyamines on Ca(2+) and H(+)
      transport and membrane potential in pea roots. Externally applied spermine or
      putrescine (1mM) equally activated eosin yellow (EY)-sensitive Ca(2+) pumping
      across the root epidermis and caused net H(+) influx or efflux. Proton influx
      induced by spermine was suppressed by EY, supporting the mechanism in which
      Ca(2+) pump imports 2 H(+) per each exported Ca(2+). Suppression of the Ca(2+)
      pump by EY diminished putrescine-induced net H(+) efflux instead of increasing
      it. Thus, activities of Ca(2+) and H(+) pumps were coupled, likely due to the
      H(+)-pump inhibition by intracellular Ca(2+). Additionally, spermine but not
      putrescine caused a direct inhibition of H(+) pumping in isolated plasma membrane
      vesicles. Spermine, spermidine, and putrescine (1mM) induced membrane
      depolarization by 70, 50, and 35 mV, respectively. Spermine-induced
      depolarization was abolished by cation transport blocker Gd(3+), was insensitive
      to anion channels' blocker niflumate, and was dependent on external Ca(2+).
      Further analysis showed that uptake of polyamines but not polyamine-induced
      cationic (K(+)+Ca(2+)+H(+)) fluxes were a main cause of membrane depolarization.
      Polyamine increase is a common component of plant stress responses. Activation of
      Ca(2+) efflux by polyamines and contrasting effects of polyamines on net H(+)
      fluxes and membrane potential can contribute to Ca(2+) signalling and modulate a
      variety of transport processes across the plasma membrane under stress. 

PMID- 24723396
TI  - The fruit, the whole fruit, and everything about the fruit.
AB  - Fruits come in an impressive array of shapes, sizes, and consistencies, and also
      display a huge diversity in biochemical/metabolite profiles, wherein lies their
      value as rich sources of food, nutrition, and pharmaceuticals. This is in
      addition to their fundamental function in supporting and dispersing the
      developing and mature seeds for the next generation. Understanding developmental
      processes such as fruit development and ripening, particularly at the genetic
      level, was once largely restricted to model and crop systems for practical and
      commercial reasons, but with the expansion of developmental genetic and evo-devo
      tools/analyses we can now investigate and compare aspects of fruit development in
      species spanning the angiosperms. We can superimpose recent genetic discoveries
      onto the detailed characterization of fruit development and ripening conducted
      with primary considerations such as yield and harvesting efficiency in mind, as
      well as on the detailed description of taxonomically relevant characters. Based
      on our own experience we focus on two very morphologically distinct and
      evolutionary distant fruits: the capsule of opium poppy, and the grain or
      caryopsis of cereals. Both are of massive economic value, but because of very
      different constituents; alkaloids of varied pharmaceutical value derived from
      secondary metabolism in opium poppy capsules, and calorific energy fuel derived
      from primary metabolism in cereal grains. Through comparative analyses in these
      and other fruit types, interesting patterns of regulatory gene function
      diversification and conservation are beginning to emerge. 

PMID- 24723395
TI  - Retention of OsNMD3 in the cytoplasm disturbs protein synthesis efficiency and
      affects plant development in rice.
AB  - The ribosome is the basic machinery for translation, and biogenesis of ribosomes
      involves many coordinated events. However, knowledge about ribosomal dynamics in
      higher plants is very limited. This study chose a highly conserved trans-factor,
      the 60S ribosomal subunit nuclear export adaptor NMD3, to characterize the
      mechanism of ribosome biogenesis in the monocot plant Oryza sativa (rice). O.
      sativa NMD3 (OsNMD3) shares all the common motifs and shuttles between the
      nucleus and cytoplasm via CRM1/XPO1. A dominant negative form of OsNMD3 with a
      truncated nuclear localization sequence (OsNMD3(DeltaNLS)) was retained in the
      cytoplasm, consequently interfering with the release of OsNMD3 from pre-60S
      particles and disturbing the assembly of ribosome subunits. Analyses of the
      transactivation activity and cellulose biosynthesis level revealed low protein
      synthesis efficiency in the transgenic plants compared with the wild-type plants.
      Pharmaceutical treatments demonstrated structural alterations in ribosomes in the
      transgenic plants. Moreover, global expression profiles of the wild-type and
      transgenic plants were investigated using the Illumina RNA sequencing approach.
      These expression profiles suggested that overexpression of OsNMD3(DeltaNLS)
      affected ribosome biogenesis and certain basic pathways, leading to pleiotropic
      abnormalities in plant growth. Taken together, these results strongly suggest
      that OsNMD3 is important for ribosome assembly and the maintenance of normal
      protein synthesis efficiency. 

PMID- 24723397
TI  - Programmed cell death activated by Rose Bengal in Arabidopsis thaliana cell
      suspension cultures requires functional chloroplasts.
AB  - Light-grown Arabidopsis thaliana cell suspension culture (ACSC) were subjected to
      mild photooxidative damage with Rose Bengal (RB) with the aim of gaining a better
      understanding of singlet oxygen-mediated defence responses in plants.
      Additionally, ACSC were treated with H2O2 at concentrations that induced
      comparable levels of protein oxidation damage. Under low to medium light
      conditions, both RB and H2O2 treatments activated transcriptional defence
      responses and inhibited photosynthetic activity, but they differed in that
      programmed cell death (PCD) was only observed in cells treated with RB. When dark
      grown ACSC were subjected to RB in the light, PCD was suppressed, indicating that
      the singlet oxygen-mediated signalling pathway in ACSC requires functional
      chloroplasts. Analysis of up-regulated transcripts in light-grown ACSC, treated
      with RB in the light, showed that both singlet oxygen-responsive transcripts and
      transcripts with a key role in hormone-activated PCD (i.e. ethylene and jasmonic
      acid) were present. A co-regulation analysis proved that ACSC treated with RB
      exhibited higher correlation with the conditional fluorescence (flu) mutant than
      with other singlet oxygen-producing mutants or wild-type plants subjected to high
      light. However, there was no evidence for the up-regulation of EDS1, suggesting
      that activation of PCD was not associated with the EXECUTER- and EDS1-dependent
      signalling pathway described in the flu mutant. Indigo Carmine and Methylene
      Violet, two photosensitizers unable to enter chloroplasts, did not activate
      transcriptional defence responses in ACSC; however, whether this was due to their
      location or to their inherently low singlet oxygen quantum efficiencies was not
      determined. 

PMID- 24723398
TI  - Identification of the glucosyltransferase gene that supplies the p-hydroxybenzoyl
      glucose for 7-polyacylation of anthocyanin in delphinium.
AB  - In delphiniums (Delphinium grandiflorum), blue flowers are produced by the
      presence of 7-polyacylated anthocyanins. The polyacyl moiety is composed of
      glucose and p-hydroxybenzoic acid (pHBA). The 7-polyacylation of anthocyanin has
      been shown to be catalysed by two different enzymes, a glucosyltransferase and an
      acyltransferase; both enzymes utilize p-hydroxybenzoyl-glucose (pHBG) as a bi
      functional (Zwitter) donor. To date, however, the enzyme that synthesizes pHBG
      and the gene that encodes it have not been elucidated. Here, five delphinium
      cultivars were investigated and found to show reduced or undetectable 7
      polyacylation activity; these cultivars synthesized delphinidin 3-O-rutinoside
      (Dp3R) to produce mauve sepals. One cultivar showed a deficiency for the acyl
      glucose-dependent anthocyanin 7-O-glucosyltransferase (AA7GT) necessary for
      mediating the first step of 7-polyacylation. The other four cultivars showed both
      AA7GT activity and DgAA7GT expression; nevertheless, pHBG accumulation was
      significantly reduced compared with wild-type cultivars, whereas p-glucosyl
      oxybenzoic acid (pGBA) was accumulated. Three candidate cDNAs encoding a UDP
      glucose-dependent pHBA glucosyltransferase (pHBAGT) were identified. A
      phylogenetic analysis of DgpHBAGT amino acid sequences showed a close
      relationship with UGTs that act in acyl-glucose synthesis in other plant species.
      Recombinant DgpHBAGT protein synthesized pHBG and had a high preference for pHBA
      in vitro. Mutant cultivars accumulating pGBA had very low expression of DgpHBAGT,
      whereas expression during the development of sepals and tissues in a wild
      cultivar showed a close correlation to the level of accumulation of pHBG. These
      results support the conclusion that DgpHBAGT is responsible for in vivo synthesis
      of pHBG in delphiniums. 

PMID- 24723399
TI  - Members of the tomato FRUITFULL MADS-box family regulate style abscission and
      fruit ripening.
AB  - The tomato (Solanum lycopersicum) protein MADS-RIN plays important roles in fruit
      ripening. In this study, the functions of two homologous tomato proteins, FUL1
      and FUL2, which contain conserved MIKC domains that typify plant MADS-box
      proteins, and which interact with MADS-RIN, were analysed. Transgenic functional
      analysis showed that FUL1 and FUL2 function redundantly in fruit ripening
      regulation, but exhibit distinct roles in the regulation of cellular
      differentiation and expansion. Over-expression of FUL2 in tomato resulted in a
      pointed tip at the blossom end of the fruit, together with a thinner pericarp,
      reduced stem diameter, and smaller leaves, but no obvious phenotypes resulted
      from FUL1 over-expression. Dual suppression of FUL1 and FUL2 substantially
      inhibited fruit ripening by blocking ethylene biosynthesis and decreasing
      carotenoid accumulation. In addition, the levels of transcript corresponding to
      ACC SYNTHASE2 (ACS2), which plays a key role in ethylene biosynthesis, were
      significantly decreased in the FUL1/FUL2 knock-down tomato fruits. Overall, our
      results suggest that FUL proteins can regulate tomato fruit ripening through fine
      tuning ethylene biosynthesis and the expression of ripening-related genes. 

PMID- 24723400
TI  - ALY proteins participate in multifaceted Nep1Mo-triggered responses in Nicotiana
      benthamiana and Arabidopsis thaliana.
AB  - Previously, it was found that Nep1Mo (a Nep1-like protein from Magnaporthe
      oryzae) could trigger a variety of plant responses, including stomatal closure,
      hypersensitive cell death (HCD), and defence-related gene expression, in
      Nicotiana benthamiana. In this study, it was found that Nep1Mo-induced cell death
      could be inhibited by the virus-induced gene silencing of NbALY916 in N.
      benthamiana. NbALY916-silenced plants showed impaired Nep1Mo-induced stomatal
      closure, decreased Nep1Mo-induced production of hydrogen peroxide (H2O2) and
      nitric oxide (NO) in guard cells, and reduced Nep1Mo-induced resistance against
      Phytophthora nicotianae. It also found that the deletion of AtALY4, an orthologue
      of NbALY916 in Arabidopsis thaliana, impaired Nep1Mo-triggered stomatal closure,
      HCD, and defence-related gene expression. The compromised stomatal closure
      observed in the NbALY916-silenced plants and AtALY4 mutants was inhibited by the
      application of H2O2 and sodium nitroprusside (an NO donor), and both Nep1Mo and
      H2O2 stimulated guard cell NO synthesis. Conversely, NO-induced stomatal closure
      was found not to require H2O2 synthesis; and NO treatment did not induce H2O2
      production in guard cells. Taken together, these results demonstrate that the
      NbAlY916/AtAlY4-H2O2-NO pathway mediates multiple Nep1Mo-triggered responses,
      including stomatal closure, HCD, and defence-related gene expression. 

PMID- 24723401
TI  - Down-regulation of AUXIN RESPONSE FACTORS 6 and 8 by microRNA 167 leads to floral
      development defects and female sterility in tomato.
AB  - Auxin regulates the expression of diverse genes that affect plant growth and
      development. This regulation requires AUXIN RESPONSE FACTORS (ARFs) that bind to
      the promoter regions of these genes. ARF6 and ARF8 in Arabidopsis thaliana are
      required to promote inflorescence stem elongation and late stages of petal,
      stamen, and gynoecium development. All seed plants studied thus far have ARF6 and
      ARF8 orthologues as well as the microRNA miR167, which targets ARF6 and ARF8.
      Whether these genes have broadly conserved roles in flower development is not
      known. To address this question, the effects of down-regulation of ARF6 and ARF8
      were investigated through transgenic expression of Arabidopsis MIR167a in tomato,
      which diverged from Arabidopsis before the radiation of dicotyledonous plants
      approximately 90-112 million years ago. The transgenic tomato plants
      overexpressing MIR167a exhibited reductions in leaf size and internode length as
      well as shortened petals, stamens, and styles. More significantly, the transgenic
      plants were female-sterile as a result of failure of wild-type pollen to
      germinate on the stigma surface and/or to grow through the style. RNA-Seq
      analysis identified many genes with significantly altered expression patterns,
      including those encoding products with functions in 'transcription regulation',
      'cell wall' and 'lipid metabolism' categories. Putative orthologues of a subset
      of these genes were also differentially expressed in Arabidopsis arf6 arf8 mutant
      flowers. These results thus suggest that ARF6 and ARF8 have conserved roles in
      controlling growth and development of vegetative and flower organs in dicots. 

PMID- 24723402
TI  - Interactions between light intensity and phosphorus nutrition affect the
      phosphate-mining capacity of white lupin (Lupinus albus L.).
AB  - Light intensity affects photosynthetic carbon (C) fixation and the supply of
      carbon to roots. To evaluate interactions between carbon supply and phosphorus
      (P) supply, effects of light intensity on sucrose accumulation, root growth,
      cluster root formation, carboxylate exudation, and P uptake capacity were studied
      in white lupin (Lupinus albus L.) grown hydroponically with either 200 umol m(-2)
      s(-1) or 600 umol m(-2) s(-1) light and a sufficient (50 uM P) or deficient (1 uM
      P) P supply. Plant biomass and root:shoot ratio increased with increasing light
      intensity, particularly when plants were supplied with sufficient P. Both low P
      supply and increasing light intensity increased the production of cluster roots
      and citrate exudation. Transcripts of a phosphoenol pyruvate carboxylase gene
      (LaPEPC3) in cluster roots (which is related to the exudation of citrate),
      transcripts of a phosphate transporter gene (LaPT1), and P uptake all increased
      with increasing light intensity, under both P-sufficient and P-deficient
      conditions. Across all four experimental treatments, increased cluster root
      formation and carboxylate exudation were associated with lower P concentration in
      the shoot and greater sucrose concentration in the roots. It is suggested that C
      in excess of shoot growth capabilities is translocated to the roots as sucrose,
      which serves as both a nutritional signal and a C-substrate for carboxylate
      exudation and cluster root formation. 

PMID- 24723403
TI  - Inclusion of vein traits improves predictive power for the leaf economic
      spectrum: a response to Sack et al. (2013).
AB  - Our model for the worldwide leaf economics spectrum (LES) based on venation
      networks (Blonder et al., 2011, 2013) was strongly criticized by Sack et al.
      (2013) in this journal. Here, we show that the majority of criticisms by Sack et
      al. are based on mathematical and conceptual misunderstandings. Using empirical
      data from both our original study as well as others in the literature, we show
      support for our original hypothesis, that venation networks provide predictive
      power and conceptual unification for the LES. In an effort to reconcile differing
      viewpoints related to the role of leaf venation traits for the LES, we highlight
      several lines of further investigation. 

PMID- 24723405
TI  - Increasing tomato fruit quality by enhancing fruit chloroplast function. A double
      edged sword?
AB  - Fruits are generally regarded as photosynthate sinks as they rely on energy
      provided by sugars transported from leaves to carry out the highly demanding
      processes of development and ripening; eventually these imported photosynthates
      also contribute to the fruit organoleptic properties. Three recent reports have
      revealed, however, that transcriptional factors enhancing chloroplast development
      in fruit may result in higher contents not only of tomato fruit-specialized
      metabolites but also of sugars. In addition to suggesting new ways to improve
      fruit quality by fortifying fruit chloroplasts and plastids, these results
      prompted us to re-evaluate the importance of the contribution of
      chloroplasts/photosynthesis to fruit development and ripening. 

PMID- 24723404
TI  - Gamma-secretase subunits associate in intracellular membrane compartments in
      Arabidopsis thaliana.
AB  - Gamma-secretase is a multisubunit complex with intramembrane proteolytic
      activity. In humans it was identified in genetic screens of patients suffering
      from familial forms of Alzheimer's disease, and since then it was shown to
      mediate cleavage of more than 80 substrates, including amyloid precursor protein
      or Notch receptor. Moreover, in animals, gamma-secretase was shown to be involved
      in regulation of a wide range of cellular events, including cell signalling,
      regulation of endocytosis of membrane proteins, their trafficking, and
      degradation. Here we show that genes coding for gamma-secretase homologues are
      present in plant genomes. Also, amino acid motifs crucial for gamma-secretase
      activity are conserved in plants. Moreover, all gamma-secretase subunits:
      PS1/PS2, APH-1, PEN-2, and NCT colocalize and interact with each other in
      Arabidopsis thaliana protoplasts. The intracellular localization of gamma
      secretase subunits in Arabidopsis protoplasts revealed a distribution in
      endomembrane system compartments that is consistent with data from animal
      studies. Together, our data may be considered as a starting point for analysis of
      gamma-secretase in plants. 

PMID- 24723406
TI  - The Arabidopsis transcription factor IIB-related protein BRP4 is involved in the
      regulation of mitotic cell-cycle progression during male gametogenesis.
AB  - Male gametogenesis in angiosperms involves two rounds of mitosis that are
      essential for the generation of two sperm cells to achieve double fertilization,
      a distinct event in the sexual reproduction of flowering plants. Precise
      regulation of mitosis during male gametogenesis is critically important for the
      establishment of the male germline. However, the molecular mechanisms underlying
      mitotic division during male gametophyte development have not been characterized
      fully. Here, we report that the Arabidopsis transcription initiation factor TFIIB
      related protein BRP4 is involved in the regulation of mitotic cell-cycle
      progression during male gametogenesis. BRP4 was expressed predominately in
      developing male gametophytes. Knockdown expression of BRP4 by a native promoter
      driven RNA interference construct in Arabidopsis resulted in arrest of the
      mitotic progression of male gametophytes, leading to a defect in pollen
      development. Moreover, we showed that the level of expression of a gene encoding
      a subunit of the origin recognition complex, ORC6, was decreased in BRP4
      knockdown plants, and that the ORC6 knockdown transgenic plants phenocopied the
      male gametophyte defect observed in BRP4 knockdown plants, suggesting that ORC6
      acts downstream of BRP4 to mediate male mitotic progression. Taken together, our
      results reveal that BRP4 plays an important role in the regulation of mitotic
      cell-cycle progression during male gametogenesis. 

PMID- 24723407
TI  - Over-expression of the Arabidopsis proton-pyrophosphatase AVP1 enhances
      transplant survival, root mass, and fruit development under limiting phosphorus
      conditions.
AB  - Phosphorus (P), an element required for plant growth, fruit set, fruit
      development, and fruit ripening, can be deficient or unavailable in agricultural
      soils. Previously, it was shown that over-expression of a proton-pyrophosphatase
      gene AVP1/AVP1D (AVP1DOX) in Arabidopsis, rice, and tomato resulted in the
      enhancement of root branching and overall mass with the result of increased
      mineral P acquisition. However, although AVP1 over-expression also increased
      shoot biomass in Arabidopsis, this effect was not observed in tomato under
      phosphate-sufficient conditions. AVP1DOX tomato plants exhibited increased
      rootward auxin transport and root acidification compared with control plants.
      AVP1DOX tomato plants were analysed in detail under limiting P conditions in
      greenhouse and field trials. AVP1DOX plants produced 25% (P=0.001) more
      marketable ripened fruit per plant under P-deficient conditions compared with the
      controls. Further, under low phosphate conditions, AVP1DOX plants displayed
      increased phosphate transport from leaf (source) to fruit (sink) compared to
      controls. AVP1DOX plants also showed an 11% increase in transplant survival
      (P<0.01) in both greenhouse and field trials compared with the control plants.
      These results suggest that selection of tomato cultivars for increased proton
      pyrophosphatase gene expression could be useful when selecting for cultivars to
      be grown on marginal soils. 

PMID- 24723408
TI  - Reticulate evolution in Panicum (Poaceae): the origin of tetraploid broomcorn
      millet, P. miliaceum.
AB  - Panicum miliaceum (broomcorn millet) is a tetraploid cereal, which was among the
      first domesticated crops, but is now a minor crop despite its high water use
      efficiency. The ancestors of this species have not been determined; we aimed to
      identify likely candidates within the genus, where phylogenies are poorly
      resolved. Nuclear and chloroplast DNA sequences from P. miliaceum and a range of
      diploid and tetraploid relatives were used to develop phylogenies of the diploid
      and tetraploid species. Chromosomal in situ hybridization with genomic DNA as a
      probe was used to characterize the genomes in the tetraploid P. miliaceum and a
      tetraploid accession of P. repens. In situ hybridization showed that half the
      chromosomes of P. miliaceum hybridized more strongly with labelled genomic DNA
      from P. capillare, and half with labelled DNA from P. repens. Genomic DNA probes
      differentiated two sets of 18 chromosomes in the tetraploid P. repens. Our
      phylogenetic data support the allotetraploid origin of P. miliaceum, with the
      maternal ancestor being P. capillare (or a close relative) and the other genome
      being shared with P. repens. Our P. repens accession was also an allotetraploid
      with two dissimilar but closely related genomes, the maternal genome being
      similar to P. sumatrense. Further collection of Panicum species, particularly
      from the Old World, is required. It is important to identify why the water
      efficient P. miliaceum is now of minimal importance in agriculture, and it may be
      valuable to exploit the diversity in this species and its ancestors. 

PMID- 24723410
TI  - Cancer: a disease of highly efficient and creative genome management?

PMID- 24723409
TI  - Photosynthesis of C3, C3-C4, and C4 grasses at glacial CO2.
AB  - Most physiology comparisons of C3 and C4 plants are made under current or
      elevated concentrations of atmospheric CO2 which do not reflect the low CO2
      environment under which C4 photosynthesis has evolved. Accordingly,
      photosynthetic nitrogen (PNUE) and water (PWUE) use efficiency, and the activity
      of the photosynthetic carboxylases [Rubisco and phosphoenolpyruvate carboxylase
      (PEPC)] and decarboxylases [NADP-malic enzyme (NADP-ME) and phosphoenolpyruvate
      carboxykinase (PEP-CK)] were compared in eight C4 grasses with NAD-ME, PCK, and
      NADP-ME subtypes, one C3 grass, and one C3-C4 grass grown under ambient (400 MUl
      l(-1)) and glacial (180 MUl l(-1)) CO2. Glacial CO2 caused a smaller reduction of
      photosynthesis and a greater increase of stomatal conductance in C4 relative to
      C3 and C3-C4 species. Panicum bisulcatum (C3) acclimated to glacial [CO2] by
      doubling Rubisco activity, while Rubisco was unchanged in Panicum milioides (C3
      C4), possibly due to its high leaf N and Rubisco contents. Glacial CO2 up
      regulated Rubisco and PEPC activities in concert for several C4 grasses, while
      NADP-ME and PEP-CK activities were unchanged, reflecting the high control exerted
      by the carboxylases relative to the decarboxylases on the efficiency of C4
      metabolism. Despite having larger stomatal conductance at glacial CO2, C4 species
      maintained greater PWUE and PNUE relative to C3-C4 and C3 species due to higher
      photosynthetic rates. Relative to other C4 subtypes, NAD-ME and PEP-CK grasses
      had the highest PWUE and PNUE, respectively; relative to C3, the C3-C4 grass had
      higher PWUE and similar PNUE at glacial CO2. Biomass accumulation was reduced by
      glacial CO2 in the C3 grass relative to the C3-C4 grass, while biomass was less
      reduced in NAD-ME grasses compared with NADP-ME and PCK grasses. Under glacial
      CO2, high resource use efficiency offers a key evolutionary advantage for the
      transition from C3 to C4 photosynthesis in water- and nutrient-limited
      environments. 

PMID- 24723411
TI  - Promoting replication and repair in the right place at the right time (comment on
      DOI 10.1002/bies.201300161).

PMID- 24723412
TI  - Can a minimal replicating construct be identified as the embodiment of cancer?
AB  - Genomic instability is a hallmark of cancer. Cancer cells that exhibit abnormal
      chromosomes are characteristic of most advanced tumours, despite the potential
      threat represented by accumulated genetic damage. Carcinogenesis involves a loss
      of key components of the genetic and signalling molecular networks; hence some
      authors have suggested that this is part of a trend of cancer cells to behave as
      simple, minimal replicators. In this study, we explore this conjecture and
      suggest that, in the case of cancer, genomic instability has an upper limit that
      is associated with a minimal cancer cell network. Such a network would include
      (for a given microenvironment) the basic molecular components that allow cells to
      replicate and respond to selective pressures. However, it would also exhibit
      internal fragilities that could be exploited by appropriate therapies targeting
      the DNA repair machinery. The implications of this hypothesis are discussed. 

PMID- 24723416
TI  - Accelerated Versus Traditional Rehabilitation After Anterior Talofibular Ligament
      Reconstruction for Chronic Lateral Instability of the Ankle in Athletes.
AB  - BACKGROUND: Although several reconstruction procedures for chronic lateral ankle
      instability using autografts have been reported, all have recommended
      postoperative immobilization and a nonweightbearing period. HYPOTHESIS:
      Reconstructive surgery with a gracilis autograft using an interference fit
      anchoring system for chronic lateral ankle instability enables early accelerated
      rehabilitation and recovery with a return to activity without requiring
      immobilization. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: A
      total of 33 patients (33 feet) who underwent reconstruction of the anterior
      talofibular ligament with a gracilis autograft using interference screws were
      included; 15 were followed for 4 weeks with postoperative cast immobilization
      (group I), while 18 were followed with accelerated rehabilitation without
      immobilization (group A). Clinical and radiological results were evaluated based
      on the Karlsson and Peterson score, talar tilt angle, anterior displacement of
      the talus on stress radiography, and time between surgery and return to full
      athletic activity. RESULTS: The mean Karlsson and Peterson scores before and 2
      years after surgery were the following: for group I: 62.3 +/- 4.7 (range, 54-72)
      and 94.4 +/- 7.1 (range, 76-100), respectively (P < .001), and for group A: 64.1
      +/- 4.8 (range, 57-70) and 91.7 +/- 7.7 (range, 74-100), respectively (P < .001).
      The mean difference in the talar tilt angle compared with the contralateral side
      and mean displacement of the talus on stress radiography before and 2 years after
      surgery were the following: for group I: 8.7 degrees  +/- 2.6 degrees  and 7.7 +/
      1.8 mm and 3.8 degrees  +/- 1.5 degrees  and 4.0 +/- 1.6 mm, respectively, and
      for group A: 10.5 degrees  +/- 3.4 degrees  and 8.7 +/- 2.1 mm and 4.3 degrees 
      +/- 1.8 degrees  and 4.3 +/- 1.2 mm, respectively. Radiography revealed
      significantly improved postoperative outcomes in both groups (P < .0001). No
      significant differences in the score and any parameters on stress radiography
      were evident at 2 years after surgery between the groups. The mean time between
      surgery and return to full athletic activity was significantly higher in group I
      (18.5 +/- 3.5 weeks) than in group A (13.4 +/- 2.2 weeks) (P < .0001). No cases
      of reinjury were reported, and no differences in athletic performance ability
      were observed between the groups. CONCLUSION: Patients in group A returned to
      full athletic activity 5 weeks earlier than those in group I, demonstrating the
      advantage of accelerated rehabilitation after surgery.

PMID- 24723417
TI  - Publication and level of evidence trends in the American Journal of Sports
      Medicine from 1996 to 2011.
AB  - BACKGROUND: There has been recent increased emphasis on the publication quality
      and levels of evidence in orthopaedic sports medicine clinical research. The
      American Journal of Sports Medicine (AJSM) began publishing levels of evidence in
      the abstracts of clinical articles in 2005. PURPOSE: To analyze trends in the
      characteristics and levels of evidence of articles published in AJSM. STUDY
      DESIGN: Meta-analysis. METHODS: All articles in AJSM from 1996, 2001, 2006, and
      2011 were analyzed. Articles were analyzed for type: clinical original research,
      basic science, current concepts review, and case report. Clinical articles were
      assigned a level of evidence from 1 to 4 and categorized as therapeutic,
      prognostic, diagnostic, or economic. Descriptive information was collected
      regarding funding, authorship, and study characteristics. Statistics were
      calculated using chi2 tests. RESULTS: A total of 795 articles were analyzed. From
      1996 to 2011, there has been a significant increase in the percentage of level 1
      and 2 articles (9.4% to 23.0%; P=.007) and a significant decrease in the
      percentage of level 3, 4, and 5 articles (55.1% to 45.1%; P=.037). There was a
      significant increase in the percentage of therapeutic studies (46.8% to 68.6%;
      P=.004) and a decrease in prognostic studies (36.7% to 22.2%; P=.03). Publishing
      authors were from 31 countries, notable for a significant increase in the
      percentage of studies published by authors from outside the United States from
      1996 to 2011 (20.3% to 53.0%; P<.001). The percentage of articles reporting a
      financial conflict of interest significantly increased during this time (26.1% to
      42.2%; P=.006). CONCLUSION: From 1996 to 2011, the proportion of level 1 and 2
      evidence studies published in AJSM has increased significantly. There has been an
      increase in therapeutic studies and a decrease in prognostic studies. There has
      been an increase in the number of international studies published.

PMID- 24723418
TI  - My memory of Walter Fitch (1929-2011) and starting molecular biology and
      evolution.

PMID- 24723419
TI  - Limited gene misregulation is exacerbated by allele-specific upregulation in
      lethal hybrids between Drosophila melanogaster and Drosophila simulans.
AB  - Misregulation of gene expression is often observed in interspecific hybrids and
      is generally attributed to regulatory incompatibilities caused by divergence
      between the two genomes. However, it has been challenging to distinguish effects
      of regulatory divergence from secondary effects including developmental and
      physiological defects common to hybrids. Here, we use RNA-Seq to profile gene
      expression in F1 hybrid male larvae from crosses of Drosophila melanogaster to
      its sibling species D. simulans. We analyze lethal and viable hybrid males, the
      latter produced using a mutation in the X-linked D. melanogaster Hybrid male
      rescue (Hmr) gene and compare them with their parental species and to public data
      sets of gene expression across development. We find that Hmr has drastically
      different effects on the parental and hybrid genomes, demonstrating that hybrid
      incompatibility genes can exhibit novel properties in the hybrid genetic
      background. Additionally, we find that D. melanogaster alleles are preferentially
      affected between lethal and viable hybrids. We further determine that many of the
      differences between the hybrids result from developmental delay in the Hmr(+)
      hybrids. Finally, we find surprisingly modest expression differences in hybrids
      when compared with the parents, with only 9% and 4% of genes deviating from
      additivity or expressed outside of the parental range, respectively. Most of
      these differences can be attributed to developmental delay and differences in
      tissue types. Overall, our study suggests that hybrid gene misexpression is prone
      to overestimation and that even between species separated by approximately 2.5
      Ma, regulatory incompatibilities are not widespread in hybrids. 

PMID- 24723420
TI  - The genotype-phenotype map of yeast complex traits: basic parameters and the role
      of natural selection.
AB  - Most phenotypic traits are controlled by many genes, but a global picture of the
      genotype-phenotype map (GPM) is lacking. For example, in no species do we know
      generally how many genes affect a trait and how large these effects are. It is
      also unclear to what extent GPMs are shaped by natural selection. Here we address
      these fundamental questions using the reverse genetic data of 220 morphological
      traits in 4,718 budding yeast strains, each of which lacks a nonessential gene.
      We show that 1) the proportion of genes affecting a trait varies from <1% to
      >30%, averaging 6%, 2) most traits are impacted by many more small-effect genes
      than large-effect genes, and 3) the mean effect of all nonessential genes on a
      trait decreases precipitously as the estimated importance of the trait to fitness
      increases. An analysis of 3,116 yeast gene expression traits in 754 gene-deletion
      strains reveals a similar pattern. These findings illustrate the power of genome
      wide reverse genetics in genotype-phenotype mapping, uncover an enormous range of
      genetic complexity of phenotypic traits, and suggest that the GPM of cellular
      organisms has been shaped by natural selection for mutational robustness. 

PMID- 24723421
TI  - Why human disease-associated residues appear as the wild-type in other species:
      genome-scale structural evidence for the compensation hypothesis.
AB  - Many human-disease associated amino acid residues (DARs) appear as the wild-type
      in other species. This phenomenon is commonly explained by the presence of
      compensatory residues in these other species that alleviate the deleterious
      effects of the DARs. The general validity of this hypothesis, however, is
      unclear, because few compensatory residues have been identified. Here we test the
      compensation hypothesis by assembling and analyzing 1,077 DARs located in 177
      proteins of known crystal structures. Because destabilizing protein structures is
      a primary reason why DARs are deleterious, we focus on protein stability in this
      analysis. We discover that, in species where a DAR represents the wild-type, the
      destabilizing effect of the DAR is generally lessened by the observed amino acid
      substitutions in the spatial proximity of the DAR. This and other findings
      provide genome-scale evidence for the compensation hypothesis and have important
      implications for understanding epistasis in protein evolution and for using
      animal models of human diseases. 

PMID- 24723422
TI  - Inferring the evolutionary history of primate microRNA binding sites: overcoming
      motif counting biases.
AB  - The first microRNAs (miRNAs) were identified as essential, conserved regulators
      of gene expression, targeting the same genes across nearly all bilaterians.
      However, there are also prominent examples of conserved miRNAs whose functions
      appear to have shifted dramatically, sometimes over very brief periods of
      evolutionary time. To determine whether the functions of conserved miRNAs are
      stable or dynamic over evolutionary time scales, we have here defined the neutral
      turnover rates of short sequence motifs in predicted primate 3'-UTRs. We find
      that commonly used approaches to quantify motif turnover rates, which use a
      presence/absence scoring in extant lineages to infer ancestral states, are
      inherently biased to infer the accumulation of new motifs, leading to the false
      inference of continually increasing regulatory complexity over time. Using a
      maximum likelihood approach to reconstruct individual ancestral nucleotides, we
      observe that binding sites of conserved miRNAs in fact have roughly equal numbers
      of gain and loss events relative to ancestral states and turnover extremely
      slowly relative to nearly identical permutations of the same motif. Contrary to
      case studies showing examples of functional turnover, our systematic study of
      miRNA binding sites suggests that in primates, the regulatory roles of conserved
      miRNAs are strongly conserved. Our revised methodology may be used to quantify
      the mechanism by which regulatory networks evolve. 

PMID- 24723423
TI  - OrthoMaM v8: a database of orthologous exons and coding sequences for comparative
      genomics in mammals.
AB  - Comparative genomic studies extensively rely on alignments of orthologous
      sequences. Yet, selecting, gathering, and aligning orthologous exons and protein
      coding sequences (CDS) that are relevant for a given evolutionary analysis can be
      a difficult and time-consuming task. In this context, we developed OrthoMaM, a
      database of ORTHOlogous MAmmalian Markers describing the evolutionary dynamics of
      orthologous genes in mammalian genomes using a phylogenetic framework. Since its
      first release in 2007, OrthoMaM has regularly evolved, not only to include newly
      available genomes but also to incorporate up-to-date software in its analytic
      pipeline. This eighth release integrates the 40 complete mammalian genomes
      available in Ensembl v73 and provides alignments, phylogenies, evolutionary
      descriptor information, and functional annotations for 13,404 single-copy
      orthologous CDS and 6,953 long exons. The graphical interface allows to easily
      explore OrthoMaM to identify markers with specific characteristics (e.g., taxa
      availability, alignment size, %G+C, evolutionary rate, chromosome location). It
      hence provides an efficient solution to sample preprocessed markers adapted to
      user-specific needs. OrthoMaM has proven to be a valuable resource for
      researchers interested in mammalian phylogenomics, evolutionary genomics, and has
      served as a source of benchmark empirical data sets in several methodological
      studies. OrthoMaM is available for browsing, query and complete or filtered
      downloads at http://www.orthomam.univ-montp2.fr/. 

PMID- 24723424
TI  - Major depressive disorder and bone mass in adolescents and young adults.
AB  - Depression has been associated with reduced bone mass in adults, but the
      mechanisms remain unclear. In addition, little is known about the association
      between depression and bone health during growth and development. To address this
      knowledge gap, we examined bone density and structure in 222 adolescents and
      young adults (69% females, mean +/- SD age: 19.0 +/- 1.5 years), enrolled within
      1 month of starting a selective serotonin reuptake inhibitor (SSRI) or
      unmedicated. Psychiatric functioning was assessed with self-report and researcher
      administered instruments, including the Longitudinal Interval Follow-up
      Evaluation for Adolescents (A-LIFE). Anthropometric and laboratory measures
      included dual-energy x-ray absorptiometry and peripheral quantitative computed
      tomography scans. Linear multivariable regression analysis tested the association
      between depression and bone mass, after accounting for relevant confounders. The
      presence of current depression was associated with a significant reduction in age
      sex-height-race-specific bone mineral density (BMD) and content (BMC) of total
      body less head and lumbar spine. The findings varied by assessment method with
      self-report scales, capturing symptom severity over the prior week or two,
      yielding the weakest associations. Depression was also associated with reduced
      cortical thickness and a trend for increased endosteal circumference. In
      contrast, generalized anxiety disorder was not associated with bone deficits. In
      sum, depressive illness is associated with significantly lower bone mass in
      youths. Future investigations must examine whether bone recovery is possible
      following depression remission or whether remedial interventions are warranted to
      optimize bone mass in order to minimize the long-term risk of osteoporosis.

PMID- 24723425
TI  - Clinical presentation of prostate cancer in black South Africans.
AB  - BACKGROUND: Compared with White Americans, Black American men are at a
      significant increased risk of presenting with prostate cancer (PCa) and
      associated mortality, suggesting a link to African-ancestry. However, PCa status
      within Africa is largely unknown. We address the clinical presentation of PCa
      within Black South African men. METHODS: Over 1,000 participants with or without
      PCa have enrolled in the Southern African Prostate Cancer Study (SAPCS). Using
      genome-wide profiling we establish a unique within Africa population
      substructure. Adjusting for age, clinical variables were assessed, compared
      against Black Americans and between rural and urban localities while addressing
      potential socio-demographic confounders. RESULTS: We report a significant
      difference in the distribution of prostate specific antigen (PSA) levels skewed
      towards higher PSA levels in the PCa cases (83.0% present with a PSA >= 20 ug/L;
      median PSA = 98.8 ug/L) relative to men with no detectable PCa (18.5% present
      with a PSA >= 20 ug/L; median PSA = 9.1 ug/L). Compared with Black Americans,
      Black South Africans presented with significantly more aggressive disease defined
      by Gleason score >7 (17% and 36%, respectively) and PSA >= 20 ug/L (17.2% and
      83.2%, respectively). We report exasperated disease aggression defined by Gleason
      score >7 (P = 0.0042) and poorly differentiated tumor grade (P < 0.0001) within
      rural versus urban localities. CONCLUSION: Black South African men present with
      higher PSA levels and histopathological tumor grade compared with Black
      Americans, which is further escalated in men from rural localities. Our data
      suggests that lack of PSA testing may be contributing to an aggressive PCa
      disease phenotype within South African men.

PMID- 24723426
TI  - The human long noncoding RNA lnc-IL7R regulates the inflammatory response.
AB  - Long noncoding RNAs (lncRNAs), once thought to be transcriptional noise, have
      been recently shown to regulate a variety of biological processes. However, there
      is not much knowledge regarding their roles in the inflammatory response. In this
      study, we performed human lncRNA microarray assays and identified a number of
      lncRNAs that demonstrated altered expression in response to LPS stimulation. Of
      these lncRNAs, lnc-IL7R, which overlaps with the 3'untranslated region (3'UTR) of
      the human interleukin-7 receptor alpha-subunit gene (IL7R) gene, was
      significantly upregulated in LPS-treated cells. Functionally, lnc-IL7R was
      capable of diminishing the LPS-induced inflammatory response, demonstrated by
      elevated expression of LPS-induced E-selectin, VCAM-1, IL-6, and IL-8 in lnc-IL7R
      knockdown cells. Mechanistically, we found that lnc-IL7R knockdown diminished
      trimethylation of histone H3 at lysine 27 (H3K27me3), a hallmark of silent
      transcription, at the proximal promoters of the inflammatory mediators. Our data
      suggest that lnc-IL7R contributes another layer of complexity in regulation of
      the inflammatory response. 

PMID- 24723428
TI  - The impact of comorbid gastroesophageal reflux disease on endoscopic sinus
      surgery quality-of-life outcomes.
AB  - BACKGROUND: Chronic rhinosinusitis (CRS) and gastroesophageal reflux disease
      (GERD) are common entities that overlap in patient demographics. The
      pathophysiologic role of GERD has yet to be elucidated, but it is postulated that
      extraesophageal reflux may contribute to worsening symptoms of CRS. This study
      seeks to investigate whether patients with CRS with and without a history of GERD
      experience comparable quality-of-life (QOL) improvement after endoscopic sinus
      surgery (ESS). METHODS: An adult cohort (n = 229) with medically refractory CRS
      was prospectively assessed following ESS using 3 disease-specific QOL constructs.
      A patient subset with a history of comorbid GERD was retrospectively identified
      (n = 72) and preoperative and postoperative QOL were compared to patients without
      GERD (n = 157). RESULTS: Patients with comorbid GERD and CRS were comparable
      across all baseline patient characteristics (p > 0.050) with the exception of
      patients with a history of GERD; those patients were less likely to have
      undergone allergy testing (p < 0.002) and were older (53.8 years vs 47.6; p <
      0.002). Similarly, baseline objective and subjective measures of disease were
      comparable between patients with CRS with and without GERD (p > 0.050). Both
      groups experienced significant QOL improvement across all QOL constructs (p <=
      0.021), and no difference was detected in the magnitude of that improvement
      between patients with and without a history of GERD (p > 0.050). Similarly,
      patients on active medical therapy for GERD (n = 49) had QOL gains comparable to
      patients not reporting GERD medical therapy (p > 0.050). CONCLUSION: Patients
      electing ESS for CRS with and without comorbid GERD have comparable baseline
      characteristics and QOL outcomes following surgery.

PMID- 24723427
TI  - The prevalence of bacterial infection in acute rhinosinusitis: a Systematic
      review and meta-analysis.
AB  - OBJECTIVES/HYPOTHESIS: To systematically assess the prevalence of bacterial
      infection in adults with acute rhinosinusitis (ARS). METHODS: Electronic
      databases were systematically searched for relevant studies published up to June
      2012. RESULTS: Twenty-nine articles, evaluating a total of 9,595 patients with a
      clinical diagnosis of ARS, were included in the study. Of these, 14 (48%) studies
      required radiographic confirmation of sinusitis, one study (3%) required evidence
      of purulence, 10 studies (35%) required both for inclusion in the study
      population, and four studies (14%) required neither. The random effects model
      estimate of prevalence of bacterial growth on all cultures was 53.7% (CI 48.4%
      59.0%), ranging from 52.5% (CI 46.7%-58.3%) in studies requiring radiographic
      confirmation of sinusitis to 61.1% (CI 54.0%-68.1%) in studies requiring neither
      radiographic evidence nor purulence on exam. Studies that obtained cultures from
      antral swab had a prevalence of bacterial growth of 61.0% (CI 54.7%-67.2%),
      whereas those utilizing endoscopic meatal sampling had a prevalence of 32.9% (CI
      19.0%-46.8%). CONCLUSIONS: Few studies evaluate the recovery of bacteria via
      culture in adults with a diagnosis of ABRS or ARS based on clinical criteria
      alone. With radiographic and/or endoscopic confirmation, antral puncture and
      endoscopically guided cultures produce positive bacterial cultures in
      approximately one-half of patients. Opportunities exist to improve diagnostic
      accuracy for bacterial infection in ARS.

PMID- 24723429
TI  - TET2 deficiency inhibits mesoderm and hematopoietic differentiation in human
      embryonic stem cells.
AB  - Ten-eleven-translocation 2 (TET2) belongs to the TET protein family that
      catalyzes the conversion of 5-methylcytosine into 5-hydroxymethylcytosine and
      plays a central role in normal and malignant adult hematopoiesis. Yet the role of
      TET2 in human hematopoietic development remains largely unknown. Here, we show
      that TET2 expression is low in human embryonic stem cell (ESC) lines and
      increases during hematopoietic differentiation. shRNA-mediated TET2 knockdown had
      no effect on the pluripotency of various ESCs. However, it skewed their
      differentiation into neuroectoderm at the expense of endoderm and mesoderm both
      in vitro and in vivo. These effects were rescued by reintroducing the targeted
      TET2 protein. Moreover, TET2-driven differentiation was dependent on NANOG
      transcriptional factor. Indeed, TET2 bound to NANOG promoter and in TET2
      deficient cells the methylation of the NANOG promoter correlated with a decreased
      in NANOG expression. The altered differentiation resulting from TET2 knockdown in
      ESCs led to a decrease in both the number and the cloning capacities of
      hematopoietic progenitors. These defects were due to an increased apoptosis and
      an altered gene expression profile, including abnormal expression of neuronal
      genes. Intriguingly, when TET2 was knockdown in hematopoietic cells, it increased
      hematopoietic development. In conclusion, our work suggests that TET2 is involved
      in different stages of human embryonic development, including induction of the
      mesoderm and hematopoietic differentiation.

PMID- 24723430
TI  - Clinical profiles of multiple myeloma in Asia-An Asian Myeloma Network study.
AB  - The incidence of multiple myeloma (MM) is known to be variable according to
      ethnicity. However, the differences in clinical characteristics between ethnic
      groups are not well-defined. In Asian countries, although the incidence of MM has
      been lower than that of Western countries, there is growing evidence that MM is
      increasing rapidly. The Asian Myeloma Network decided to initiate the first
      multinational project to describe the clinical characteristics of MM and the
      clinical practices in Asia. Data were retrospectively collected from 23 centers
      in 7 countries and regions. The clinical characteristics at diagnosis, survival
      rates and initial treatment of 3,405 symptomatic MM patients were described.
      Median age was 62 years (range, 19-106), with 55.6% of being male. Median overall
      survival (OS) was 47 months (95% CI 44.0-50.0). Stem cell transplantation was
      performed in 666 patients who showed better survival rates (79 vs. 41 months, P <
      0.001). The first-line treatments of 2,970 patients were analyzed. The overall
      response rate was 71% including very good partial response or better in 31% of
      the 2,660 patients those were able to be evaluated. New drugs including
      bortezomib, thalidomide, and lenalidomide were used in 36% of 2,970 patients and
      affected OS when used as a first-line treatment.

PMID- 24723431
TI  - A new and highly sensitive resonance Rayleigh scattering assay for lysozyme using
      aptamer-nanogold as a probe.
AB  - Gold nanoparticles (GN), 10 nm in size, were modified by using lysozyme aptamer
      (Apt) to obtain a stable Apt-GN probe in pH 8.05 Tris/HCl buffer solutions
      containing 0.04 mol/L NaCl. Upon addition of lysozyme (LYS), it reacted with the
      Apt of the probe to form a very stable Apt-LYS complex and to release GNs, which
      aggregated to form large clusters with a resonance Rayleigh scattering (RRS) peak
      at 368 nm. The enhanced peak intensity, DeltaI, was linear to the LYS
      concentration in the range 0.2-5.2 nmol/L, with a detection limit of 0.05 nmol/L.
      The influence of foreign substance was tested, and the results showed that this
      RRS method has high selectivity. This Apt-GN RRS method was applied to the
      analysis of LYS in a real sample, with satisfactory results.

PMID- 24723432
TI  - Lack of influence of DAT1 and DRD2 gene variants on antidepressant response in
      generalized anxiety disorder.
AB  - OBJECTIVE: Although antidepressant drugs are used as first-line intervention to
      treat patients with generalized anxiety disorder (GAD), only one-third of
      patients respond positively to treatment. In our study, we investigated whether
      functional genetic polymorphisms in the dopamine active transporter 1 (DAT1) and
      dopamine receptor D2 (DRD2) may play a role in antidepressant treatment response
      in GAD. METHODS: We examined 156 patients diagnosed with GAD who received
      venlafaxine Extended-Release (XR) treatment as part of an 18-month relapse
      prevention study to determine whether variation in these genes had an effect on
      treatment response after 6 months of open-label treatment. Genotypes were
      obtained for rs1076560 (DRD2), rs1800497 (DRD2), rs2550948 (DAT1), and a variable
      number tandem repeat in the 3' untranslated region of the DAT1 gene using
      standard methods. RESULTS: Results show that none of the tested variants were
      associated with treatment response to venlafaxine XR in GAD. Genotype and allele
      frequencies did not differ statistically significantly between responders and non
      responders using either the Hamilton Anxiety or Clinical Global Impressions of
      Improvement Scale at 6 months. CONCLUSIONS: Although we detected no association
      in our sample, future studies using larger samples and more comprehensive gene
      coverage are needed to evaluate potential effects of dopaminergic variants on
      antidepressant treatment response in anxiety disorders.

PMID- 24723433
TI  - Reply: To PMID 24375485.

PMID- 24723434
TI  - Effects of the dietary incorporation of olive leaves on growth performance,
      digestibility, blood parameters and meat quality of growing pigs.
AB  - BACKGROUND: In a preliminary study the oxidative stability and tocopherol content
      of pork meat were shown to be improved by olive leaf (OL) feed supplementation at
      50 and 100 g kg(-1) . However, growth performance was affected negatively.
      Therefore the objective of the present study was to assess the influence of OL
      supplementation at a lower level on feed digestibility, growth performance and
      meat quality. RESULTS: Pigs were fed a basal diet (control), a basal diet with 25
      g OL kg(-1) (OL2.5) or a basal diet with 50 g OL kg(-1) (OL5). The incorporation
      of OL significantly decreased growth rates (P = 0.010) and backfat thickness (P =
      0.035) and increased feed/gain ratio (P = 0.032) in the OL5 group. Feed/gain
      ratio increased more for females (P = 0.001). The incorporation of OL decreased
      the crude fat (P = 0.006) and protein (P = 0.037) digestibility of both OL diets.
      Nevertheless, OL was effective in increasing the tocopherol content of meat (P =
      0.009). However, meat from pigs fed the OL diets showed similar conjugated diene
      content, pH and colour parameters to that from pigs fed the control diet, even
      after 6 days of storage at 4  degrees C. CONCLUSION: The data indicate that olive
      leaves may be included in pig diets at 25 g kg(-1) in order to improve the
      tocopherol content of meat without excessively compromising growth performance.

PMID- 24723435
TI  - Laryngotracheal separation in an infant with severe dysgenesis of the larynx.
AB  - OBJECTIVES/HYPOTHESIS: We describe management of an infant with chronic
      aspiration as a result of severe and rarely described laryngeal dysgenesis.
      RESULTS: A neonate with severe maldevelopment of the laryngeal structures
      required tracheostomy for respiratory distress on day-of-life 1, but the patient
      continued to have aspiration pneumonias. After failing to improve with
      conservative measures, the infant underwent laryngotracheal separation (LTS),
      which was successful in preventing aspiration. The patient has had no further
      pneumonias. CONCLUSIONS: The presented case illustrates that LTS may be
      considered a safe and effective initial treatment option for chronic aspiration
      in select infants with severe dysgenesis of the larynx.

PMID- 24723436
TI  - AFAP1L1, a novel associating partner with vinculin, modulates cellular morphology
      and motility, and promotes the progression of colorectal cancers.
AB  - We have previously identified actin filament-associated protein 1-like 1
      (AFAP1L1) as a metastasis-predicting marker for spindle cell sarcomas by gene
      expression profiling, and demonstrated that AFAP1L1 is involved in the cell
      invasion process by in vitro analyses. However, its precise molecular function
      has not been fully elucidated, and it remains unknown whether AFAP1L1 could be a
      prognostic marker and/or therapeutic target of other malignancies. In this study,
      we found a marked elevation of AFAP1L1 gene expression in colorectal cancer (CRC)
      tissues as compared to the adjacent normal mucosa. Multivariate analysis revealed
      that AFAP1L1 was an independent and significant factor for the recurrence of
      rectal cancers. Moreover, the addition of the AFAP1L1 expression level to the
      lymph node metastasis status provided more predictive information regarding
      postoperative recurrence in rectal cancers. AFAP1L1-transduced CRC cells
      exhibited a rounded shape, increased cell motility on planar substrates, and
      resistance to anoikis in vitro. AFAP1L1 localized to the ringed structure of the
      invadopodia, together with vinculin, and AFAP1L1 was identified as a novel
      associating partner of vinculin by immunoprecipitation assay. AFAP1L1-transduced
      cells showed accelerated tumor growth in vivo, presumably reflecting the anoikis
      resistance of these AFAP1L1-expressing cells. Furthermore, the local
      administration of a siRNA against AFAP1L1 significantly suppressed the in vivo
      tumor growth of xenografts, suggesting that AFAP1L1 might be a candidate
      therapeutic target for CRCs. These results suggest that AFAP1L1 plays a role in
      the progression of CRCs by modulating cell shape and motility and by inhibiting
      anoikis, presumably through interactions with vinculin-including protein
      complexes. 

PMID- 24723437
TI  - Stimulation through very late antigen-4 and -5 improves the multifunctionality
      and memory formation of CD8+ T cells.
AB  - T cells express multiple integrin molecules. The significance of signaling
      through these molecules on acquisition of T-cell effector functions and memory
      formation capacity remains largely unknown. Moreover, the impact of stimulation
      through these signals on the generation of T cells for adoptive immunotherapy has
      not been elucidated. In this study, using a recombinant fragment of fibronectin,
      CH-296, we demonstrated that stimulation via very late Ag (VLA)-4 and VLA-5 in
      human and BALB/c mouse CD8(+) T cells, in combination with TCR stimulation,
      enhances effector multifunctionality and in vivo memory formation. Using TCR
      transgenic mouse-derived CD8(+) T cells expressing TCR specific for the syngeneic
      CMS5 fibrosarcoma-derived tumor Ag, we showed that stimulation by CH-296 improved
      the ability of tumor-specific CD8(+) T cells to inhibit CMS5 tumor growth when
      adoptively transferred into hosts with progressing tumors. Improved antitumor
      effects were associated with decreased infiltration of Foxp3(+) CD4(+) Treg cells
      in tumors. These results suggest that stimulation via VLA-4 and VLA-5 modulates
      the qualities of effector T cells and could potentially increase the efficacy of
      adoptive therapy against cancer.

PMID- 24723438
TI  - Clarithromycin overcomes resistance to lenalidomide and dexamethasone in multiple
      myeloma.
AB  - The combination of clarithromycin, lenalidomide and dexamethasone (BiRd) has led
      to highly durable responses in newly diagnosed myeloma. However, the ability of
      clarithromycin to overcome resistance to lenalidomide and dexamethasone (Rd) is
      not known. To study this, we performed a retrospective analysis of 24 patients
      with myeloma for which clarithromycin was added to Rd at the time of progression
      on Rd. The median number of prior therapies was 3 (range 1-8). The best response
      was complete response (CR) in one (4.2%), very good partial response (VGPR) in
      one (4.2%) and partial response in eight (33.3%) patients. Ten patients, 41.7%
      (95% CI: 22.1, 63.4), achieved >=PR. The median time to response was 4.4 months
      (range 1-13.6 months) and the median duration of response was 6.9 months (range 3
      52.2 months). The clinical benefit rate (CR + VGPR + PR + MR) was 45.8% (95% CI
      25.6, 67.2). The median progression-free survival was 4 months. Median overall
      survival was 25 months with a median follow-up of 27.5 months. The regimen was
      well tolerated and only 2 patients needed a clarithromycin dose reduction.
      Addition of clarithromycin to Rd can overcome resistance to Rd in a subset of
      patients and lead to durable clinical responses.

PMID- 24723439
TI  - Evaluation of trapping parameters of gamma-rays irradiated Dy3+ -doped LaPO4
      phosphors.
AB  - Thermoluminescence (TL) materials are widely used in radiation measurements. The
      best-known applications of TL materials are in the dosimetry of ionizing
      radiation, and in CTV screen phosphors, scintillators, X-ray laser materials,
      etc. The TL glow curve and its kinetic parameters for annealed LaPO4 at different
      constant temperatures and for Dy(3+) -doped LaPO4 phosphors irradiated by gamma
      rays are reported here. The samples were irradiated using a (60) Co gamma-ray
      source at a dose of 10 Gy and the heating rate used for TL measurements was 5
      oC/s. The samples were characterized using X-ray diffraction (XRD), Fourier
      transform infrared, transmission electron microscopy and TL techniques. The XRD
      pattern shows that the prepared phosphor has a good crystalline structure with an
      average crystallite size of ~ 18 nm. The samples show good TL peaks for 0.05, 0.1
      and 0.2 mole % doping concentrations of Dy(3+) ions and anneal above 400 oC. The
      TL glow curve characteristics of annealed LaPO4 and Dy(3+) -doped LaPO4 were
      analyzed and trapping parameters calculated using various methods. All TL glow
      curves obey the second-order kinetics with a single glow peak, which reveals that
      only one set of trapping parameter is set for a particular temperature. The TL
      sensitivity was found to depend upon the annealing temperature and Dy(3+) doping
      concentration. The prepared sample may be a new nano phosphor and be useful in TL
      dosimetry.

PMID- 24723440
TI  - Potent inhibitors of human matriptase-1 based on the scaffold of sunflower
      trypsin inhibitor.
AB  - Sunflower trypsin inhibitor-1 (SFTI-1), a bicyclic tetradecapeptide, has become a
      versatile tool as a scaffold for the development of the inhibitors of
      therapeutically relevant serine proteases, among them matriptase and kallikreins.
      Herein, we report the rational design of potent monocyclic and bicyclic
      inhibitors of human matriptase-1. We found that the presence of positive charge
      and lack of bulky residues at the peptide N-terminus is required for the
      maintenance of inhibitory activity. Replacement of the N-terminal glycine residue
      by lysine allowed for the chemical conjugation with a fluorophor via the epsilon
      amino group without significant loss of inhibitory activity. Head-to-tail and
      side-chain-to-tail cyclization resulted in potent inhibitors with comparable
      activities against matriptase-1. The most potent synthetic bicyclic inhibitor
      found in this study (Ki  = 2.6 nM at pH 7.6) is a truncated version of SFTI-1
      (cyclo-KRCTKSIPPRCH) lacking a C-terminal proline and aspartate residue. It
      combines an internal disulfide bond with a peptide macrocycle that is formed
      through side-chain-to-tail cyclization of the epsilon-amino group of an N
      terminal lysine and a C-terminal proline.

PMID- 24723444
TI  - Helicobacter pylori might contribute to nonalcoholic fatty liver disease-related
      cardiovascular events by releasing prothrombotic and proinflammatory factors.

PMID- 24723445
TI  - Shifting effects of physiological integration on performance of a clonal plant
      during submergence and de-submergence.
AB  - BACKGROUND AND AIMS: Submergence and de-submergence are common phenomena
      encountered by riparian plants due to water level fluctuations, but little is
      known about the role of physiological integration in clonal plants (resource
      sharing between interconnected ramets) in their adaptation to such events. Using
      Alternanthera philoxeroides (alligator weed) as an example, this study tested the
      hypotheses that physiological integration will improve growth and photosynthetic
      capacity of submerged ramets during submergence and will promote their recovery
      following de-submergence. METHODS: Connected clones of A. philoxeroides, each
      consisting of two ramet systems and a stolon internode connecting them, were
      grown under control (both ramet systems untreated), half-submerged (one ramet
      system submerged and the other not submerged), fully submerged (both ramet
      systems submerged), half-shaded (one ramet system shaded and the other not
      shaded) and full-shaded (both ramet systems shaded) conditions for 30 d and then
      de-submerged/de-shaded for 20 d. The submerged plants were also shaded to very
      low light intensities, mimicking typical conditions in turbid floodwater. KEY
      RESULTS: After 30 d of submergence, connections between submerged and non
      submerged ramets significantly increased growth and carbohydrate accumulation of
      the submerged ramets, but decreased the growth of the non-submerged ramets. After
      20 d of de-submergence, connections did not significantly affect the growth of
      either de-submerged or non-submerged ramets, but de-submerged ramets had high
      soluble sugar concentrations, suggesting high metabolic activities. The shift
      from significant effects of integration on both submerged and non-submerged
      ramets during the submergence period to little effect during the de-submergence
      period was due to the quick recovery of growth and photosynthesis. The effects of
      physiological integration were not found to be any stronger under submergence/de
      submergence than under shading/de-shading. CONCLUSIONS: The results indicate that
      it is not just the beneficial effects of physiological integration that are
      crucial to the survival of riparian clonal plants during periods of submergence,
      but also the ability to recover growth and photosynthesis rapidly after de
      submergence, which thus allows them to spread.

PMID- 24723446
TI  - Influence of the variation of geometrical and topological traits on light
      interception efficiency of apple trees: sensitivity analysis and metamodelling
      for ideotype definition.
AB  - BACKGROUND AND AIMS: The impact of a fruit tree's architecture on its performance
      is still under debate, especially with regard to the definition of varietal
      ideotypes and the selection of architectural traits in breeding programmes. This
      study aimed at providing proof that a modelling approach can contribute to this
      debate, by using in silico exploration of different combinations of traits and
      their consequences on light interception, here considered as one of the key
      parameters to optimize fruit tree production. METHODS: The variability of organ
      geometrical traits, previously described in a bi-parental population, was used to
      simulate 1- to 5-year-old apple trees (Malus * domestica). Branching sequences
      along trunks observed during the first year of growth of the same hybrid trees
      were used to initiate the simulations, and hidden semi-Markov chains previously
      parameterized were used in subsequent years. Tree total leaf area (TLA) and
      silhouette to total area ratio (STAR) values were estimated, and a sensitivity
      analysis was performed, based on a metamodelling approach and a generalized
      additive model (GAM), to analyse the relative impact of organ geometry and
      lateral shoot types on STAR. KEY RESULTS: A larger increase over years in TLA
      mean and variance was generated by varying branching along trunks than by varying
      organ geometry, whereas the inverse was observed for STAR, where mean values
      stabilized from year 3 to year 5. The internode length and leaf area had the
      highest impact on STAR, whereas long sylleptic shoots had a more significant
      effect than proleptic shoots. Although the GAM did not account for interactions,
      the additive effects of the geometrical factors explained >90% of STAR variation,
      but much less in the case of branching factors. CONCLUSIONS: This study
      demonstrates that the proposed modelling approach could contribute to screening
      architectural traits and their relative impact on tree performance, here viewed
      through light interception. Even though trait combinations and antagonism will
      need further investigation, the approach opens up new perspectives for breeding
      and genetic selection to be assisted by varietal ideotype definition.

PMID- 24723447
TI  - An update on receptor-like kinase involvement in the maintenance of plant cell
      wall integrity.
AB  - BACKGROUND: Plant cell walls form the interface between the cells and their
      environment. They perform different functions, such as protecting cells from
      biotic and abiotic stress and providing structural support during development.
      Maintenance of the functional integrity of cell walls during these different
      processes is a prerequisite that enables the walls to perform their particular
      functions. The available evidence suggests that an integrity maintenance
      mechanism exists in plants that is capable of both detecting wall integrity
      impairment caused by cell wall damage and initiating compensatory responses to
      maintain functional integrity. The responses involve 1-aminocyclopropane-1
      carboxylic acid (ACC), jasmonic acid, reactive oxygen species and calcium-based
      signal transduction cascades as well as the production of lignin and other cell
      wall components. Experimental evidence implicates clearly different signalling
      molecules, but knowledge regarding contributions of receptor-like kinases to this
      process is less clear. Different receptor-like kinase families have been
      considered as possible sensors for perception of cell wall damage; however,
      strong experimental evidence that provides insights into functioning exists for
      very few kinases. SCOPE AND CONCLUSIONS: This review examines the involvement of
      cell wall integrity maintenance in different biological processes, defines what
      constitutes plant cell wall damage that impairs functional integrity, clarifies
      which stimulus perception and signal transduction mechanisms are required for
      integrity maintenance and assesses the available evidence regarding the functions
      of receptor-like kinases during cell wall integrity maintenance. The review
      concludes by discussing how the plant cell wall integrity maintenance mechanism
      could form an essential component of biotic stress responses and of plant
      development, functions that have not been fully recognized to date.

PMID- 24723448
TI  - New views of tapetum ultrastructure and pollen exine development in Arabidopsis
      thaliana.
AB  - BACKGROUND AND AIMS: The Arabidopsis thaliana pollen cell wall is a complex
      structure consisting of an outer sporopollenin framework and lipid-rich coat, as
      well as an inner cellulosic wall. Although mutant analysis has been a useful tool
      to study pollen cell walls, the ultrastructure of the arabidopsis anther has
      proved to be challenging to preserve for electron microscopy. METHODS: In this
      work, high-pressure freezing/freeze substitution and transmission electron
      microscopy were used to examine the sequence of developmental events in the
      anther that lead to sporopollenin deposition to form the exine and the dramatic
      differentiation and death of the tapetum, which produces the pollen coat. KEY
      RESULTS: Cryo-fixation revealed a new view of the interplay between sporophytic
      anther tissues and gametophytic microspores over the course of pollen
      development, especially with respect to the intact microspore/pollen wall and the
      continuous tapetum epithelium. These data reveal the ultrastructure of
      tapetosomes and elaioplasts, highly specialized tapetum organelles that
      accumulate pollen coat components. The tapetum and middle layer of the anther
      also remain intact into the tricellular pollen and late uninucleate microspore
      stages, respectively. CONCLUSIONS: This high-quality structural information,
      interpreted in the context of recent functional studies, provides the groundwork
      for future mutant studies where tapetum and microspore ultrastructure is
      assessed.

PMID- 24723449
TI  - Simple simultaneous determination of butylated hydroquinone (TBHQ) and butylated
      hydroxyanisole (BHA) antioxidants in oil using high-performance liquid
      chromatography with chemiluminescence detection.
AB  - A highly sensitive and convenient high-performance liquid chromatography
      technique coupled with chemiluminescence detection for the simultaneous
      determination butylated hydroquinone (TBHQ) and butylated hydroxyanisole (BHA) in
      oil is established. The detection is based on the inhibitory effect on the CL
      reaction between luminol and potassium ferricyanide in an alkaline medium.
      Samples were separated through a reverse-phase C18 column using a mobile phase of
      methanol and water (80: 20, v/v) at a flow rate of 0.5 mL/min. The effects of
      various parameters including mobile phase, flow rate and chemiluminescence regent
      were studied. Under optimum conditions, both TBHQ and BHA showed good linear
      relationships in the range 1 * 10(-7) -1 * 10(-5) g/mL with detection limits of
      24 and 33 ng/mL, respectively. The proposed method is simple and sensitive, with
      low costs. The method was successfully applied for the quantification of TBHQ and
      BHA in sesame oil. The possible inhibition mechanism is also discussed briefly.

PMID- 24723450
TI  - In vitro and in vivo characterization of irreversible mutant-selective EGFR
      inhibitors that are wild-type sparing.
AB  - Patients with non-small cell lung carcinoma (NSCLC) with activating mutations in
      epidermal growth factor receptor (EGFR) initially respond well to the EGFR
      inhibitors erlotinib and gefitinib. However, all patients relapse because of the
      emergence of drug-resistant mutations, with T790M mutations accounting for
      approximately 60% of all resistance. Second-generation irreversible EGFR
      inhibitors are effective against T790M mutations in vitro, but retain affinity
      for wild-type EGFR (EGFR(WT)). These inhibitors have not provided compelling
      clinical benefit in T790M-positive patients, apparently because of dose-limiting
      toxicities associated with inhibition of EGFR(WT). Thus, there is an urgent
      clinical need for therapeutics that overcome T790M drug resistance while sparing
      EGFR(WT). Here, we describe a lead optimization program that led to the discovery
      of four potent irreversible 2,4-diaminopyrimidine compounds that are EGFR mutant
      (EGFR(mut)) selective and have been designed to have low affinity for EGFR(WT).
      Pharmacokinetic and pharmacodynamic studies in H1975 tumor-bearing mice showed
      that exposure was dose proportional resulting in dose-dependent EGFR modulation.
      Importantly, evaluation of normal lung tissue from the same animals showed no
      inhibition of EGFR(WT). Of all the compounds tested, compound 3 displayed the
      best efficacy in EGFR(L858R/T790M)-driven tumors. Compound 3, now renamed CO
      1686, is currently in a phase I/II clinical trial in patients with EGFR(mut)
      advanced NSCLC that have received prior EGFR-directed therapy.

PMID- 24723451
TI  - Culture dimensionality influences the resistance of glioblastoma stem-like cells
      to multikinase inhibitors.
AB  - Sunitinib, an inhibitor of kinases, including VEGFR and platelet-derived growth
      factor receptor (PDGFR), efficiently induces apoptosis in vitro in glioblastoma
      (GBM) cells, but does not show any survival benefit in vivo. One detrimental
      aspect of current in vitro models is that they do not take into account the
      contribution of extrinsic factors to the cellular response to drug treatment.
      Here, we studied the effects of substrate properties including elasticity,
      dimensionality, and matrix composition on the response of GBM stem-like cells
      (GSC) to chemotherapeutic agents. Thirty-seven cell cultures, including GSCs,
      parenchymal GBM cells, and GBM cell lines, were treated with nine antitumor
      compounds. Contrary to the expected chemoresistance of GSCs, these cells were
      more sensitive to most agents than GBM parenchymal cells or GBM cell lines
      cultured on flat (two-dimensional; 2D) plastic or collagen-coated surfaces.
      However, GSCs cultured in collagen-based three-dimensional (3D) environments
      increased their resistance, particularly to receptor tyrosine kinase inhibitors,
      such as sunitinib, BIBF1120, and imatinib. Differences in substrate rigidity or
      matrix components did not modify the response of GSCs to the inhibitors.
      Moreover, the MEK-ERK and PI3K-Akt pathways, but not PDGFR, mediate at least in
      part, this dimensionality-dependent chemoresistance. These findings suggest that
      survival of GSCs on 2D substrates, but not in a 3D environment, relies on kinases
      that can be efficiently targeted by sunitinib-like inhibitors. Overall, our data
      may help explain the lack of correlation between in vitro and in vivo models used
      to study the therapeutic potential of kinase inhibitors, and provide a rationale
      for developing more robust drug screening models.

PMID- 24723452
TI  - Immunotherapy for hepatoma using a dual-function vector with both
      immunostimulatory and pim-3-silencing effects.
AB  - Tumorigenesis is an immortalization process in which the growth of normal cells
      is uncontrolled and programmed cell death is suppressed. Molecular biologic and
      immunologic studies have revealed that the aberrant expression of some proto
      oncogenes boosts proliferation and inhibits apoptosis, which is vital for tumor
      development. The hypofunction of the host immune system also drives the
      development and metastasis of malignant tumors. Pim-3, a member of the Pim
      family, is aberrantly expressed in several cancers. Data suggest that Pim-3
      inhibits apoptosis by phosphorylating the proapoptotic BH3-only protein Bad.
      Here, we constructed a dual-function small hairpin RNA (shRNA) vector containing
      an shRNA targeting Pim-3 and a TLR7-stimulating ssRNA. Stimulation with this bi
      functional vector in vitro promoted significant apoptosis of Hepa1-6 cells by
      regulating the expression of apoptosis-related proteins and induced secretion of
      type I IFNs. Most importantly, this bi-functional vector more effectively
      inhibited subcutaneous Hepa1-6 cell growth than did single shRNA and ssRNA
      treatment in vivo. Natural killer (NK), CD4(+) T, and CD8(+) T cells and
      macrophages were required for effective tumor suppression, and CD4(+) T cells
      were shown to play a helper role in the activation of NK cells, possibly by
      regulating the secretion of Th1 or Th2 cytokines. This ssRNA-shRNA bi-functional
      vector may represent a promising approach for tumor therapy.

PMID- 24723453
TI  - Coleusin factor, a novel anticancer diterpenoid, inhibits osteosarcoma growth by
      inducing bone morphogenetic protein-2-dependent differentiation.
AB  - Coleusin factor is a diterpenoid compound isolated from the root of a tropical
      plant, Coleus forskohlii. Although Coleusin factor has been reported to suppress
      proliferation of and induce apoptosis in several types of cancer cells, the
      effects of Coleusin factor on osteosarcoma and the underlying mechanism are still
      not fully understood. In this study, we show that Coleusin factor treatment
      potently inhibits the growth of osteosarcoma cells associated with G(1) cell
      cycle arrest. Interestingly, apoptosis and cell death are not induced. Instead,
      Coleusin factor causes osteosarcoma cells to exhibit typical properties of
      differentiated osteoblasts, including a morphologic alteration resembling
      osteoblasts, the expression of osteoblast differentiation markers, elevated
      alkaline phosphatase activity, and increased cellular mineralization. Coleusin
      factor treatment significantly increases the expression of bone morphogenetic
      protein-2 (BMP-2), a crucial osteogenic regulator, and runt-related transcription
      factor 2 (RUNX2), one of the key transcription factors of the BMP pathway. When
      BMP-2 signaling is blocked, Coleusin factor fails to inhibit cell proliferation
      and to induce osteoblast differentiation. Thus, upregulation of BMP-2 autocrine
      is critical for Coleusin factor to induce osteoblast differentiation and exert
      its anticancer effects on osteosarcoma. Importantly, administration of Coleusin
      factor inhibits the growth of osteosarcoma xenografted in nude mice without
      systemic or immunologic toxicity. Osteosarcoma is a highly aggressive cancer
      marked by the loss of normal differentiation. Coleusin factor represents a new
      type of BMP-2 inducer that restores differentiation in osteosarcoma cells. It may
      provide a promising therapeutic strategy against osteosarcoma with minimal side
      effects.

PMID- 24723454
TI  - INCAT disability score: a critical analysis of its measurement properties.
AB  - BACKGROUND: The INCAT (Inflammatory Neuropathy Cause and Treatment) disability
      score is a measure of activity limitation. It is used frequently as a primary
      endpoint in inflammatory polyneuropathy clinical trials. A comprehensive critical
      analysis of its measurement properties has not been performed. METHODS: Critical
      analysis of measurement properties. RESULTS: The INCAT disability score was
      derived based on items from Guy's Neurological Disability Scale (GNDS), a
      disability measure intended for application in multiple sclerosis. Strengths of
      the INCAT score include evaluation of upper and lower limb dysfunction, ease of
      administration (feasibility), high face validity, and high reliability.
      Weaknesses of the scale include concerns about methodological quality of
      validation studies; failure to properly capture activity limitations due to
      proximal arm weakness, or fatigue; heavy individual item weighting; and poor
      sensitivity for detection of clinically important change. CONCLUSIONS: Although
      the INCAT scale has been an effective tool in inflammatory polyneuropathy
      studies, its limitations may warrant development of new scales.

PMID- 24723455
TI  - Tracing dynamic expansion of human NK-cell subsets by high-resolution analysis of
      KIR repertoires and cellular differentiation.

PMID- 24723456
TI  - Does a parental history of cancer moderate the associations between impaired
      health status in parents and psychosocial problems in teenagers: a HUNT study.
AB  - Severe disease in a parent is associated with increased psychosocial problems in
      their children. However, moderating factors of such associations are less
      studied. In this cross-sectional population-based controlled study we examined
      the moderating effects of a history of parental cancer on the association between
      impaired health status in parents and psychosocial problems among their
      teenagers. Among families with both parents responding to the adult Health Survey
      of Nord-Trondelag County of Norway (the HUNT-2 study) 71 couples were identified
      with primary invasive cancer in one parent. Their 81 teenage children took part
      in the Young-HUNT study. These families were compared to 322 cancer-free families
      with 328 teenagers. Based on self-report data the relations between three
      variables of parental impaired health and six psychosocial problems in teenagers
      were analyzed family wise by structural equation modeling. Significant
      associations between parental and teenagers' variables were observed in eight of
      18 models. A history of parental cancer was a significant moderator which
      decreased four of eight significant associations. Such a history significantly
      weakened the associations between parental poor self-rated health and teenagers'
      anxiety/depression and school problems. A similar association of a history of
      parental cancer was found between psychological distress in parents and
      teenagers' feelings of loneliness and poor self-rated health. This study
      confirmed strong associations between impaired parental health and psychosocial
      problems in their teenagers. A history of parental cancer weakened several of the
      significant associations between parental impaired health variables and
      psychosocial problems in their teenagers. 

PMID- 24723457
TI  - SF3B1 mutations in patients with myelodysplastic syndromes: the mutation is
      stable during disease evolution.
AB  - The SF3B1 mutation can be detected in patients with myelodysplastic syndrome
      (MDS), but the report regarding the association of this mutation with other
      genetic alterations and its stability during disease progression is limited. In
      this study, SF3B1 mutations were identified in 10% of total cohort of 479 MDS
      patients and 61.8% of 34 patients with refractory anemia with ring sideroblasts
      (RARS). SF3B1 mutations were closely associated with older age, higher platelet
      counts, lower lactate dehydrogenase levels, good-risk cytogenetics, and mutations
      of DNMT3A, but inversely related to ASXL1 mutations. Most SF3B1-mutated patients
      had concurrent other genetic alterations, including DNMT3A and RUNX1 mutations.
      There was no prognostic difference between patients with SF3B1 mutations and
      those without. Sequential studies in 417 samples from 142 patients demonstrated
      that all SF3B1-mutated patients retained the same mutations during disease
      evolution with the exception of two patients who lost the mutation after
      allogeneic hematopoietic stem cell transplantation, whereas none of the SF3B1
      wild patients acquired a novel mutation during clinical follow-ups. In
      conclusion, the patients with SF3B1 mutations had distinct clinic-biologic
      features. SF3B1 mutations, accompanied with other genetic alterations, especially
      DNMT3A mutations, may play a role in the development of MDS, but have little role
      in disease progression.

PMID- 24723458
TI  - Antioxidant properties of a human neuropeptide and its protective effect on free
      radical-induced DNA damage.
AB  - Human catestatin CgA352-372 (SL21) is an endogenous neuropeptide with multiple
      biological functions. The present study aimed to evaluate the antioxidant,
      antibacterial, cytotoxic, and DNA damage protective effects of SL21 neuropeptide.
      SL21 neuropeptide generated from the C-terminus of chromogranin A (CgA) was
      synthesized by solid-phase method. Synthetic peptide was subjected to various in
      vitro antioxidant assays including the scavenging of 1,1-diphenyl-2-pycryl
      hydrazyl (DPPH), 2,2-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS(.+)
      ), and hydroxyl free radicals, metal ion chelation, inhibition of lipid
      peroxidation, and reducing power. Moreover, protective effect of SL21 on H2 O2 
      induced DNA damage was analyzed using pTZ57/RT plasmid. Methylthiazoltetrazolium
      assay was also performed to study the cytotoxic effect of SL21 neuropeptide on
      human peripheral blood mononuclear cells. Furthermore, antibacterial and
      hemolysis assays were conducted. The results demonstrated high activities of SL21
      in scavenging free radicals (DPPH, ABTS(.+) , and hydroxyl), chelating of Cu(2+)
      /Fe(2+) metal ions, reducing power, and inhibition of lipid peroxidation in a
      concentration-dependent manner. SL21 neuropeptide revealed a protective effect on
      DNA damage caused by hydroxyl radicals. Interestingly, the peptide exhibited no
      significant cytotoxicity towards peripheral blood mononuclear cells. Furthermore,
      SL21 peptide displayed antimicrobial activity against Staphylococcus aureus and
      Pseudomonas aeruginosa without any hemolytic activity on human red blood cells.
      Conclusively, the present study established SL21 (catestatin) as a novel
      antioxidative peptide that could further be investigated for its potential use as
      a pharmaceutical agent.

PMID- 24723459
TI  - Evaluation of green pepper (Capsicum annuum L.) juice on the weight gain and
      changes in lipid profile in C57BL/6 mice fed a high-fat diet.
AB  - BACKGROUND: Capsicum pepper (green pepper, Capsicum annuum L.), a natural product
      available in many countries, is considered to be a food additive, with healthful
      or medical applications. The aim of this study was to evaluate green pepper juice
      for its potential to reduce weight gain and to determine its effects on lipid
      profiles in C57BL/6 mice fed a high-fat diet. RESULTS: Mice given a high-fat diet
      with green pepper juice gained significantly less weight and showed a significant
      decrease in serum triglycerides, total cholesterol, low density lipoproteins, and
      alanine aminotransferase compared to mice given only a high-fat diet (P < 0.05).
      Systolic and diastolic blood pressure, heart rate, and blood glucose levels
      (determined by using the intraperitoneal glucose tolerance test) in mice
      administered green pepper juice were similar to those in mice in the control
      group. In addition, abdominal fat volume (subcutaneous and visceral), which was
      quantified by using 4.7 T magnetic resonance imaging, including multi-slice spin
      echo T2-weighted images, in mice administered a high-fat diet with green pepper
      juice tended to decrease compared to the fat volume of mice administered only a
      high-fat diet. CONCLUSION: These results suggest that green pepper juice, as a
      drink, may possibly be helpful in reducing weight gain by regulating the levels
      of serum lipids.

PMID- 24723460
TI  - Thymic stromal lymphopoietin and interleukin-4 mediate the pathogenesis of
      halothane-induced liver injury in mice.
AB  - Liver eosinophilia has been associated with incidences of drug-induced liver
      injury (DILI) for more than 50 years, although its role in this disease has
      remained largely unknown. In this regard, it was recently shown that eosinophils
      played a pathogenic role in a mouse model of halothane-induced liver injury
      (HILI). However, the signaling events that drove hepatic expression of eosinophil
      associated chemokines, eotaxins, eosinophil infiltration, and subsequent HILI
      were unclear. We now provide evidence implicating hepatic epithelial-derived
      cytokine thymic stromal lymphopoietin (TSLP) and type 2 immunity, in particular,
      interleukin-4 (IL-4) production, in mediating hepatic eosinophilia and injury
      during HILI. TSLP was constitutively expressed by mouse hepatocytes and increased
      during HILI. Moreover, the severity of HILI was reduced in mice deficient in
      either the TSLP receptor (TSLPR) or IL-4 and was accompanied by decreases in
      serum levels of eotaxins and hepatic eosinophilia. Similarly, concanavalin A
      induced liver injury, where type 2 cytokines and eosinophils play a significant
      role in its pathogenesis, was also reduced in TSLPR-deficient mice. Studies in
      vitro revealed that mouse and human hepatocytes produce TSLP and eotaxins in
      response to treatment with combinations of IL-4 and proinflammatory cytokines IL
      1beta and tumor necrosis factor alpha. CONCLUSION: This report provides the first
      evidence implicating roles for hepatic TSLP signaling, type 2 immunity, and
      eosinophilia in mediating liver injury caused by a drug.

PMID- 24723461
TI  - Factors influencing postconcussion and posttraumatic stress symptom reporting
      following military-related concurrent polytrauma and traumatic brain injury.
AB  - The purpose of this study was to identify factors that are predictive of, or
      associated with, high endorsement of postconcussion and posttraumatic stress
      symptoms following military-related traumatic brain injury (TBI). Participants
      were 1,600 U.S. service members (age: M = 27.1, SD = 7.1; 95.4% male) who had
      sustained a mild-to-moderate TBI and who had been evaluated by the Defense and
      Veterans Brain Injury Center at one of six military medical centers. Twenty-two
      factors were examined that included demographic, injury circumstances/severity,
      treatment/evaluation, and psychological/physical variables. Four factors were
      statistically and meaningfully associated with clinically elevated postconcussion
      symptoms: (i) low bodily injury severity, (ii) posttraumatic stress, (iii)
      depression, and (iv) military operation where wounded (p < .001, 43.2% variance).
      The combination of depression and posttraumatic stress symptoms accounted for the
      vast majority of unique variance (41.5%) and were strongly associated with, and
      predictive of, clinically elevated postconcussion symptoms [range: odds ratios
      (OR) = 4.24-7.75; relative risk (RR) = 2.28-2.51]. Five factors were
      statistically and meaningfully associated with clinically elevated posttraumatic
      stress symptoms: (i) low bodily injury severity, (ii) depression, (iii) a longer
      time from injury to evaluation, (iv) military operation where wounded, and (v)
      current auditory deficits (p < .001; 65.6% variance accounted for). Depression
      alone accounted for the vast majority of unique variance (60.0%) and was strongly
      associated with, and predictive of, clinically elevated posttraumatic stress
      symptoms (OR = 38.78; RR = 4.63). There was a very clear, strong, and clinically
      meaningful association between depression, posttraumatic stress, and
      postconcussion symptoms in this sample. Brain injury severity, however, was not
      associated with symptom reporting following TBI. 

PMID- 24723462
TI  - Response surface optimized peroxyoxalate chemiluminescence of octahydro-Schiff
      base derivative as new luminophor and study of the quenching effect of some
      cations, amino acids and cholesterol.
AB  - We report the first detailed study of the characteristics of an octahydro-Schiff
      base derivative as a new luminophor in the peroxyoxalate chemiluminescence (POCL)
      system. The effect of reagents on this new POCL system was investigated. In
      addition, the response surface methodology was used for evaluating the relative
      significance of variables in this POCL system, establishing models and
      determining optimal conditions. The quenching effect of some cations and
      compounds such as Cu(2+), Fe(3+), Hg(2+), imidazole, histidine and cholesterol on
      an optimized POCL reaction were studied. The dynamic ranges were up to
      approximaterly 100 and 175 * 10(-6) M for Cu(2+) and cholesterol respectively.
      The detection limits were 3.3 * 10(-6) m and 2.58 * 10(-6) m for Cu(2+) and
      histidine, respectively. In all cases the relative standard deviations were 4-5%
      (n = 4).

PMID- 24723463
TI  - Quartz and respirable dust in the Dutch construction industry: a baseline
      exposure assessment as part of a multidimensional intervention approach.
AB  - Quartz exposure can cause several respiratory health effects. Although quartz
      exposure has been described in several observational workplace studies, well
      designed intervention studies that investigate the effect of control strategies
      are lacking. This article describes a baseline exposure study that is part of a
      multidimensional intervention program aiming to reduce quartz exposure among
      construction workers. In this study, personal respirable dust and quartz exposure
      was assessed among 116 construction workers (bricklayers, carpenters, concrete
      drillers, demolishers, and tuck pointers). Possible determinants of exposure,
      like job, tasks, and work practices, use of control measures, and organizational
      and psychosocial factors, were explored using exposure models for respirable dust
      and quartz separately. Stratified analyses by job title were performed to
      evaluate the effect of control measures on exposure and to explore the
      association between control measures and psychosocial factors. Overall, 62% of
      all measurements exceeded the Dutch occupational exposure limit for quartz and
      11% for respirable dust. Concrete drillers and tuck pointers had the highest
      exposures for quartz and respirable dust (0.20 and 3.43mg m(-3), respectively).
      Significant predictors of elevated quartz exposure were abrasive tasks and type
      of material worked on. Surprisingly, in a univariate model, an increased
      knowledge level was associated with an increase in exposure. Although control
      measures were used infrequently, if used they resulted in approximately 40%
      reduction in quartz exposure among concrete drillers and tuck pointers. Only
      among concrete drillers, the use of control measures was associated with a higher
      score for social influence (factor 1.6); knowledge showed an inverse association
      with use of control measures for concrete drillers, demolishers, and tuck
      pointers. In conclusion, the detailed information on determinants of exposure,
      use of control measures, and constraints to use these control measures can be
      used for the determination and systematic prioritization of intervention measures
      used to design and implement our intervention strategy. This study underlines the
      need for multidisciplinary workplace exposure control strategies although larger
      study populations are necessary to determine a possible causal association
      between organizational and psychosocial factors and psychosocial factors and
      control measures. 

PMID- 24723464
TI  - Microbial biofilms--the coming of age of a research field.

PMID- 24723465
TI  - Single- and double-stranded viral RNA generate distinct cytokine and antiviral
      responses in human fetal membranes.
AB  - There has been growing interest in the role of viral infections and their
      association with adverse pregnancy outcomes. However, little is known about the
      impact viral infections have on the fetal membranes (FM). Toll-like receptors
      (TLR) are thought to play a role in infection-associated inflammation at the
      maternal-fetal interface. Therefore, the objective of this study was to
      characterize the cytokine profile and antiviral response in human FMs exposed to
      viral dsRNA, which activates TLR3, and viral ssRNA, which activates TLR8; and to
      determine the mechanisms involved. The viral dsRNA analog, Poly(I:C), induced up
      regulated secretion of MIP-1alpha, MIP-1beta, RANTES and TNF-alpha, and down
      regulated interleukin (IL)-2 and VEGF secretion. In contrast, viral ssRNA induced
      a broader panel of cytokines in the FMs by up-regulating the secretion of IL
      1beta, IL-2, IL-6, G-CSF, MCP-1, MIP-1alpha, MIP-1beta, RANTES, TNF-alpha and GRO
      alpha. Using inhibitory peptides against TLR adapter proteins, FM secretion of
      MIP-1beta and RANTES in response to Poly(I:C) was MyD88 dependent; MIP-1alpha
      secretion was dependent on MyD88 and TRIF; and TNF-alpha production was
      independent of MyD88 and TRIF. Viral ssRNA-induced FM secretion of IL-1beta, IL
      2, IL-6, G-CSF, MIP-1alpha, RANTES and GRO-alpha was dependent on MyD88 and TRIF;
      MIP-1beta was dependent upon TRIF, but not MyD88; and TNF-alpha and MCP-1
      secretion was dependent on neither. Poly(I:C), but not ssRNA, induced an FM
      antiviral response by up-regulating the expression of IFNbeta, myxovirus
      resistance A, 2',5'-oligoadenylate synthetase and apolipoprotein B mRNA-editing
      enzyme-catalytic polypeptide-like 3G. These findings demonstrate that human FMs
      respond to two viral signatures by generating distinct inflammatory
      cytokine/chemokine profiles and antiviral responses through different mechanisms.

PMID- 24723467
TI  - Clinical outcomes of biodegradable polymer drug-eluting stents for percutaneous
      coronary intervention: an updated meta-analysis of randomized controlled trials.
AB  - Biodegradable polymer drug-eluting stents (DES) are innovative concepts in the
      era of percutaneous coronary intervention. We systematically reviewed the latest
      randomized evidence on the efficacy and safety of biodegradable polymer DES as
      compared to durable polymer DES. MEDLINE, Embase, and the Cochrane database were
      searched in August 2013 for eligible randomized controlled trials (RCTs)
      comparing biodegradable polymer DES with durable polymer DES. Clinical outcomes
      of interest were mortality, myocardial infarction (MI), target lesion
      revascularization (TLR), target vessel revascularization (TVR), and stent
      thrombosis. A total of 20 RCTs randomizing 20 021 participants were included, of
      whom 11 045 were allocated to biodegradable polymer DES and 8976 to durable
      polymer DES. Treatment of biodegradable polymer DES was not associated with a
      significant reduction of any of the clinical outcomes (all-cause mortality, odds
      ratio [OR]: 0.94, 95% confidence interval [CI]: 0.80 to 1.10, P = 0.42;
      cardiovascular mortality, OR: 0.97, 95% CI: 0.79 to 1.19, P = 0.74; MI, OR: 1.07,
      95% CI: 0.91 to 1.26, P = 0.41; TLR, OR: 0.87, 95% CI: 0.69 to 1.08, P = 0.20;
      TVR, OR: 1.05, 95% CI: 0.85 to 1.28, P = 0.67; definite/probable stent
      thrombosis, OR: 0.80, 95% CI: 0.59 to 1.07, P = 0.14). Current randomized data
      indicate that clinical efficacy and safety profiles of biodegradable polymer DES
      are comparable to those of durable polymer DES. Findings from large-scale studies
      with rigorous methodology and long follow-up duration are needed. 

PMID- 24723466
TI  - A phase I dose escalation study of oral bexarotene in combination with
      intravenous decitabine in patients with AML.
AB  - The response rate of non-M3 acute myeloid leukemia (AML) to all trans retinoic
      acid has been limited. Using Affymetrix expression arrays, we found that in
      diverse AML blasts RXRA was expressed at higher levels than RARA and that mouse
      Ctsg-PML-RARA leukemia responded to bexarotene, a ligand for RXRA. We therefore
      performed a phase I study of combination bexarotene and decitabine in elderly and
      relapsed AML patients. We found that this combination was well tolerated,
      although outcomes were modest (1 CRi, and 3 PR among 19 patients). Correlative
      studies found that patients with clinical response had increased differentiation
      to bexarotene both in vivo and ex vivo, suggesting that pre-treatment analysis
      might identify a more susceptible subgroup of patients.

PMID- 24723469
TI  - Detecting protein atom correlations using correlation of probability of
      recurrence.
AB  - The dynamic cross-correlation Map(DCCM) technique has been used extensively to
      study protein dynamics. In this work, we introduce the use of the method of
      correlation of probability of recurrence (CPR) as a complementary method to
      detect correlations between protein residue atoms. Time series of the distances
      of the Calpha atoms of the beta-lactamase inhibitory protein (BLIP) from a
      reference position are analyzed using CPR and mutual information (MI). The
      results are compared to those provided by DCCM. In comparison to MI, CPR is found
      to detect more of the correlations present in DCCM. It is also able to detect a
      small number of significant correlations between distant residues that are not
      detected by DCCM.

PMID- 24723470
TI  - Phosphorylation of ABCB4 impacts its function: insights from disease-causing
      mutations.
AB  - The ABCB4 transporter mediates phosphatidylcholine (PC) secretion at the
      canalicular membrane of hepatocytes and its genetic defects cause biliary
      diseases. Whereas ABCB4 shares high sequence identity with the multidrug
      transporter, ABCB1, its N-terminal domain is poorly conserved, leading us to
      hypothesize a functional specificity of this domain. A database of ABCB4
      genotyping in a large series of patients was screened for variations altering
      residues of the N-terminal domain. Identified variants were then expressed in
      cell models to investigate their biological consequences. Two missense
      variations, T34M and R47G, were identified in patients with low-phospholipid
      associated cholelithiasis or intrahepatic cholestasis of pregnancy. The T34M and
      R47G mutated proteins showed no or minor defect, respectively, in maturation and
      targeting to the apical membrane, in polarized Madin-Darby Canine Kidney and
      HepG2 cells, whereas their stability was similar to that of wild-type (WT) ABCB4.
      By contrast, the PC secretion activity of both mutants was markedly decreased. In
      silico analysis indicated that the identified variants were likely to affect
      ABCB4 phosphorylation. Mass spectrometry analyses confirmed that the N-terminal
      domain of WT ABCB4 could undergo phosphorylation in vitro and revealed that the
      T34M and R47G mutations impaired such phosphorylation. ABCB4-mediated PC
      secretion was also increased by pharmacological activation of protein kinases A
      or C and decreased by inhibition of these kinases. Furthermore, secretion
      activity of the T34M and R47G mutants was less responsive than that of WT ABCB4
      to protein kinase modulators. CONCLUSION: We identified disease-associated
      variants of ABCB4 involved in the phosphorylation of its N-terminal domain and
      leading to decreased PC secretion. Our results also indicate that ABCB4 activity
      is regulated by phosphorylation, in particular, of N-terminal residues.

PMID- 24723471
TI  - Selection of autochthonous strains as promising starter cultures for Fior di
      Latte, a traditional cheese of southern Italy.
AB  - BACKGROUND: This paper describes the selection of promising strains intended as
      starter cultures from the autochthonous lactic acid bacteria of Fior di Latte
      cheese (Apulia region, southern Italy). RESULTS: Ninety-five isolates were
      randomly selected from whey and Fior di Latte. After preliminary characterization
      based upon Gram staining, deamination of arginine, hydrolysis of esculine and
      production of CO2 from glucose and citrate, the isolates were studied for their
      growth at different temperatures (10, 15 and 45  degrees C), with salt addition
      (20, 40 and 65 g L(-1) ) and at pH 4.4 and their acidification score in MRS broth
      after 6 and 24 h. Data were modeled through the growth index and used as input to
      run a preliminary cluster analysis and a principal component analysis. In this
      way, nine promising strains were selected and used for validation at laboratory
      level, to study the acidification score in milk and propose some possible
      microbial mixtures. CONCLUSION: This paper reports the first research focusing on
      the design of a lactic starter for the production of Fior di Latte cheese, using
      a quantitative approach based on the evaluation of growth index and acidification
      score as well as on the use of a multivariate approach to select the most
      promising nine strains.

PMID- 24723473
TI  - Validity of botulinum neurotoxin serotype H.

PMID- 24723472
TI  - Top-down proteomics in health and disease: challenges and opportunities.
AB  - Proteomics is essential for deciphering how molecules interact as a system and
      for understanding the functions of cellular systems in human disease; however,
      the unique characteristics of the human proteome, which include a high dynamic
      range of protein expression and extreme complexity due to a plethora of PTMs and
      sequence variations, make such analyses challenging. An emerging "top-down" MS
      based proteomics approach, which provides a "bird's eye" view of all proteoforms,
      has unique advantages for the assessment of PTMs and sequence variations.
      Recently, a number of studies have showcased the potential of top-down proteomics
      for the unraveling of disease mechanisms and discovery of new biomarkers.
      Nevertheless, the top-down approach still faces significant challenges in terms
      of protein solubility, separation, and the detection of large intact proteins, as
      well as underdeveloped data analysis tools. Consequently, new technological
      developments are urgently needed to advance the field of top-down proteomics.
      Herein, we intend to provide an overview of the recent applications of top-down
      proteomics in biomedical research. Moreover, we will outline the challenges and
      opportunities facing top-down proteomics strategies aimed at understanding and
      diagnosing human diseases. 

PMID- 24723474
TI  - Return of widespread chloroquine-sensitive Plasmodium falciparum to Malawi.
AB  - BACKGROUND: The return of chloroquine-sensitive Plasmodium falciparum to the
      limited area of Blantyre, Malawi, has been well demonstrated in several studies.
      METHODS: To characterize chloroquine susceptibility over a wide geographic area,
      infants and children aged 6-59 months were selected using 2-stage cluster
      sampling in 8 Malawian districts. Pyrosequencing of the pfcrt gene codon 76
      region was performed for children with asexual parasitemia. RESULTS: Of 7145
      children, 1150 had microscopic asexual parasitemia, and sequencing was performed
      in 685, of whom 1 had a chloroquine-resistant genotype. CONCLUSIONS: Systematic
      countrywide sampling demonstrates that the chloroquine pfcrt genotype has reached
      near-fixation, raising the possibility of reintroducing chloroquine for malaria
      prevention and treatment.

PMID- 24723476
TI  - Spectrofluorimetric determination of amisulpride and bumidazone in raw materials
      and tablets.
AB  - A highly sensitive, simple and rapid spectrofluorimetric method was developed for
      the determination of amisulpride (AMS) and bumidazone (BUM) in tablet form. The
      proposed method is based on measuring the native fluorescence of the studied
      drugs in methanol at 360 and 344 nm after excitation at 276 and 232 nm for AMS
      and BUM, respectively. The fluorescence-concentration plots were rectilinear over
      the ranges of 5.0-60.0 ng/mL for AMS and 0.5-5.0 ug/mL for BUM. The lower
      detection limits were 0.70 ng/mL and 0.06 ug/mL, and the lower quantification
      limits were 2.0 ng/mL and 0.18 ug/mL for AMS and BUM, respectively. The method
      was successfully applied for the analysis of AMS and BUM in commercial tablets.
      Statistical evaluation and comparison of the data obtained using the proposed and
      comparison methods revealed good accuracy and precision for the proposed method.

PMID- 24723483
TI  - Reduction in serum IL-10 levels is a surrogate marker for predicting vaso
      occlusive crisis in sickle cell disease.

PMID- 24723484
TI  - Proteomic characterization of seeds from yellow lupin (Lupinus luteus L.).
AB  - Yellow lupin (Lupinus luteus L.) is a legume crop containing a large amount of
      protein in its seeds. In this study, we constructed a seed-protein catalog to
      provide a foundation for further study of the seeds. A total of 736 proteins were
      identified in 341 2DE spots by nano-LC-MS/MS. Eight storage proteins were found
      as multiple spots in the 2DE gels. The 736 proteins correspond to 152 unique
      proteins as shown by UniRef50 clustering. Sixty-seven of the 152 proteins were
      associated with KEGG-defined pathways. Of the remaining proteins, 57 were
      classified according to a GO term. The functions of the remaining 28 proteins
      have yet to be determined. This is the first yellow lupin seed-protein catalog,
      and it contains considerably more data than previously reported for white lupin
      (L. albus L.). 

PMID- 24723485
TI  - Effect of cooking methods on cholesterol, mineral composition and formation of
      total heterocyclic aromatic amines in Muscovy drake meat.
AB  - BACKGROUND: Cholesterol, minerals and heterocyclic aromatic amines (HAAs) are of
      great importance in determining meat quality to humans and therefore of concern
      to meat consumers because of health reasons. The objective of this study was to
      evaluate the effects of various cooking methods (grilling, deep frying, pan
      frying and roasting) on the formation of total HAAs, cholesterol and mineral
      retention in Muscovy drake breast meat. Total HAAs and cholesterol were
      determined by high-performance liquid chromatography, while minerals were
      measured by atomic absorption spectroscopy. RESULTS: Muscovy drake breast meat
      cooked by deep frying had the highest content of total HAAs (31.83 ng g(-1)),
      followed by roasted (30.12 ng g(-1)), pan-fried (29.23 ng g(-1)) and grilled
      (27.34 ng g(-1)) fillets. The cholesterol content was highest in deep-fried
      fillets (59.09 mg g(-1)), followed by roasted fillets (58.61 mg g(-1)), while
      grilling resulted in the lowest cholesterol content (57.00 mg g(-1)). The mineral
      content was highest in deep-fried samples and lowest in roasted fillets.
      Magnesium retention was affected by the cooking method and was higher in deep
      fried samples (110.57%) than in grilled (97.97%), pan-fried (88.99%) and roasted
      (78.46%) fillets. Generally, the total HAA, cholesterol and mineral content in
      cooked Muscovy drake breast meat varied with the cooking method. CONCLUSION:
      Moderate consumption of deep-fried Muscovy drake meat should be encouraged, as
      deep frying increased its cholesterol, total HAA and mineral content compared
      with the other cooking methods investigated.

PMID- 24723486
TI  - Distinct transcriptional signature and immunoprofile of CIC-DUX4 fusion-positive
      round cell tumors compared to EWSR1-rearranged Ewing sarcomas: further evidence
      toward distinct pathologic entities.
AB  - Round cell sarcomas harboring CIC-DUX4 fusions have recently been described as
      highly aggressive soft tissue tumors of children and young adults. Due to partial
      morphologic and immunohistochemical overlap with Ewing sarcoma (ES), CIC-DUX4
      positive tumors have generally been classified as ES-like and managed similarly;
      however, a systematic comparison at the molecular and immunohistochemical levels
      between these two groups has not yet been conducted. Based on an initial
      observation that CIC-DUX4-positive tumors show nuclear immunoreactivity for WT1
      and ETS transcription factors, FLI1 and ERG, we performed a detailed
      immunohistochemical and molecular analysis including these markers, to further
      investigate the relationship between CIC-DUX4 tumors and ES. The study group
      included 21 CIC-DUX4-positive sarcomas and 20 EWSR1-rearranged ES.
      Immunohistochemically, CIC-DUX4 sarcomas showed membranous CD99 positivity in 18
      (86%) cases, but only 5 (24%) with a diffuse pattern, while WT1 and FLI1 were
      strongly positive in all cases. ERG was positive in 18% of cases. All ES
      expressed CD99 and FLI1, while ERG positivity was only seen in EWSR1-ERG fusion
      positive ES. WT1 was negative in all ES. Expression profiling validated by q-PCR
      revealed a distinct gene signature associated with CIC-DUX4 fusion, with
      upregulation of ETS transcription factors (ETV4, ETV1, and ETV5) and WT1, among
      top overexpressed genes compared to ES, other sarcomas and normal tissue. In
      conclusion, the distinct gene signature and immunoprofile of CIC-DUX4 sarcomas
      suggest a distinct pathogenesis from ES. The consistent WT1 expression may
      provide a useful clue in the diagnosis in the context of round cell sarcomas
      negative for EWSR1 rearrangement. (c) 2014 Wiley Periodicals, Inc. 

PMID- 24723487
TI  - Randomized phase II trial of irinotecan and bevacizumab as neo-adjuvant and
      adjuvant to temozolomide-based chemoradiation compared with temozolomide
      chemoradiation for unresectable glioblastoma: final results of the TEMAVIR study
      from ANOCEF?.
AB  - BACKGROUND: Prognosis of unresectable glioblastoma (GB) remains poor, despite
      temozolomide (TMZ)-based chemoradiation. Activity of bevacizumab (BEV) and
      irinotecan (IRI) has been reported in recurrent disease. We evaluated BEV and IRI
      as neo-adjuvant and adjuvant treatment combined with TMZ-based chemoradiation for
      unresectable GB. PATIENTS AND METHODS: Patients with unresectable GB, age 18-70,
      IK >=50 were eligible. The experimental arm (BEV/IRI) consisted of neo-adjuvant
      intravenous BEV, 10 mg/kg, and IRI, 125 mg/m(2), every 2 weeks for four cycles
      before radiotherapy (RT) (60 Gy), concomitant oral TMZ, 75 mg/m(2)/day, and BEV,
      10 mg/kg every 2 weeks. Adjuvant BEV and IRI were given every 2 weeks for 6
      months. The control arm consisted of concomitant oral TMZ, 75 mg/m(2)/day during
      RT, and 150-200 mg/m(2) for 5 days every 28 days for 6 months. The use of BEV was
      allowed at progression in the control arm. RESULTS: Patients (120) were included
      from April 2009 to January 2011. The working hypothesis was that treatment would
      increase the progression-free survival at 6 month (PFS-6) from 50% to 66%. The
      primary objective was not achieved, and only 30 out of 60 patients were alive
      without progression at 6 months (50.0% [IC95% (36.8; 63.1)] in the BEV/IRI arm
      when 37 out of 60 patients were required according to the Fleming decision rules.
      PFS-6 was 7.1 months in BEV/IRI versus 5.2 months in the control arm. The median
      overall survival was not different between the two arms (11.1 months). Main
      toxicities were three fatal intracranial bleedings, three bile duct or digestive
      perforations/infections (1 fatal), and six thrombotic episodes in the BEV/IRI
      arm, whereas there was one intracranial bleeding, two bile duct or digestive
      perforations/infections (1 fatal), and one thrombotic episode in the control arm.
      CONCLUSIONS: Neo-adjuvant and adjuvant BEV/IRI, combined with TMZ-radiation, is
      not recommended for further evaluation in the first-line treatment of
      unresectable GB. CLINICAL TRIAL REGISTRATION: Clinical trial registered under
      EUDRACT number 2008-002775-28 (NCT01022918).

PMID- 24723489
TI  - Expanding the eco-evolutionary context of herbicide resistance research.
AB  - The potential for human-driven evolution in economically and environmentally
      important organisms in medicine, agriculture and conservation management is now
      widely recognised. The evolution of herbicide resistance in weeds is a classic
      example of rapid adaptation in the face of human-mediated selection. Management
      strategies that aim to slow or prevent the evolution of herbicide resistance must
      be informed by an understanding of the ecological and evolutionary factors that
      drive selection in weed populations. Here, we argue for a greater focus on the
      ultimate causes of selection for resistance in herbicide resistance studies. The
      emerging fields of eco-evolutionary dynamics and applied evolutionary biology
      offer a means to achieve this goal and to consider herbicide resistance in a
      broader and sometimes novel context. Four relevant research questions are
      presented, which examine (i) the impact of herbicide dose on selection for
      resistance, (ii) plant fitness in herbicide resistance studies, (iii) the
      efficacy of herbicide rotations and mixtures and (iv) the impacts of gene flow on
      resistance evolution and spread. In all cases, fundamental ecology and evolution
      have the potential to offer new insights into herbicide resistance evolution and
      management.

PMID- 24723490
TI  - Mutations in the main cytoplasmic loop of the GABA(A) receptor alpha4 and delta
      subunits have opposite effects on surface expression.
AB  - We examined the role of putative trafficking sequences in two GABA(A) receptor
      subunits: alpha4 and delta. These subunits assemble with a beta subunit to form a
      subtype of GABA(A) receptor involved in generating the "tonic" outward current.
      Both alpha4 and delta subunits contain dibasic retention motifs in homologous
      positions. When basic residues are mutated to alanine in the alpha4 subunit,
      surface expression of epitope-tagged delta subunits is increased. When basic
      residues in homologous regions of the delta subunit are mutated, however, surface
      expression is reduced. We focused on the mutants that had the maximal effects to
      increase (in alpha4) or reduce (in delta) surface expression. The total
      expression of delta subunits is significantly decreased by the delta mutation,
      suggesting an effect on subunit maturation. We also examined surface expression
      of the beta2 subunit. Expression of the mutated alpha4 subunit resulted in
      increased surface expression of beta2 compared with wild-type alpha4, indicating
      enhanced forward trafficking. In contrast, mutated delta resulted in decreased
      surface expression of beta2 compared with wild-type delta and to alpha4 and beta2
      in the absence of any delta. This observation suggests that the mutated delta
      incorporates into multimeric receptors and reduces the overall forward
      trafficking of receptors. These observations indicate that the roles of
      trafficking motifs are complex, even when located in homologous positions in
      related subunits. The physiologic properties of receptors containing mutated
      subunits were not significantly affected, indicating that the mutations in the
      alpha4 subunit will be useful to enhance surface expression.

PMID- 24723488
TI  - SIE-SIES-GITMO guidelines for the management of adult peripheral T- and NK-cell
      lymphomas, excluding mature T-cell leukaemias.
AB  - BACKGROUND: In order to promote widespread adoption of appropriate clinical
      practice, the Italian Society of Hematology (SIE), and the affiliate societies
      SIES (Italian Society of Experimental Hematology) and GITMO (Italian Group for
      Bone Marrow Transplantation) established to produce guidelines in the most
      relevant hematological areas. In this article, we report the recommendations for
      management of T/NK-cell lymphomas, excluding mature T-cell leukaemias. DESIGN: By
      using the Grades of Recommendations, Assessment, Development and Evaluation
      (GRADE) system, we produced evidence-based recommendations for the key clinical
      questions that needed to be addressed by a critical appraisal of evidence. The
      consensus methodology was applied to evidence-orphan issues. RESULTS: Six courses
      of cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) or
      cyclophosphamide, doxorubicin, vincristine, etoposide and prednisone (CHOEP)
      chemotherapy were recommended for first-line therapy of patients with nodal,
      intestinal or hepatosplenic T-cell lymphomas (evidence: low; recommendation: do,
      weak). Except for ALK+ anaplastic large-cell lymphoma and elderly unfit patients,
      consolidation with high-dose chemotherapy was recommended (evidence: low;
      recommendation: do, weak). 50 Gy radiotherapy was the recommended first-line
      therapy for localized extranodal T/NK-cell lymphoma nasal type (evidence: low;
      recommendation: do, strong), while l-asparaginase-containing chemotherapy
      regimens were recommended for patients with systemic disease (evidence: very low;
      recommendation: do, strong). CONCLUSION: In adult T/NK-cell lymphomas, GRADE
      methodology was applicable to a limited number of key therapeutic issues. For the
      remaining key issues, due to lack of appraisable evidence, recommendations was
      based on consensus methodology.

PMID- 24723482
TI  - Why primate models matter.
AB  - Research involving nonhuman primates (NHPs) has played a vital role in many of
      the medical and scientific advances of the past century. NHPs are used because of
      their similarity to humans in physiology, neuroanatomy, reproduction,
      development, cognition, and social complexity-yet it is these very similarities
      that make the use of NHPs in biomedical research a considered decision. As
      primate researchers, we feel an obligation and responsibility to present the
      facts concerning why primates are used in various areas of biomedical research.
      Recent decisions in the United States, including the phasing out of chimpanzees
      in research by the National Institutes of Health and the pending closure of the
      New England Primate Research Center, illustrate to us the critical importance of
      conveying why continued research with primates is needed. Here, we review key
      areas in biomedicine where primate models have been, and continue to be,
      essential for advancing fundamental knowledge in biomedical and biological
      research.

PMID- 24723491
TI  - Structure, molecular modeling, and function of the novel potassium channel
      blocker urotoxin isolated from the venom of the Australian scorpion Urodacus
      yaschenkoi.
AB  - This communication reports the structural and functional characterization of
      urotoxin, the first K(+) channel toxin isolated from the venom of the Australian
      scorpion Urodacus yaschenkoi. It is a basic peptide consisting of 37 amino acids
      with an amidated C-terminal residue. Urotoxin contains eight cysteines forming
      four disulfide bridges with sequence similarities resembling the alpha-potassium
      channel toxin 6 (alpha-KTx-6) subfamily of peptides; it was assigned the
      systematic number of alpha-KTx-6.21. Urotoxin is a potent blocker of human
      voltage-gated potassium channel (Kv)1.2 channels, with an IC50 of 160 pM, whereas
      its affinity for other channels tested was in the nanomolar range (hKv1.1, IC50 =
      253 nM; hKv1.3, IC50 = 91 nM; and hKCa3.1, IC50 = 70 nM). The toxin had no effect
      on hKv1.4, hKv1.5, human ether-a-go-go-related gene type 1 (hERG1), or human
      ether-a-go-go-like (hELK2) channels. Multiple sequence alignments from the venom
      gland transcriptome showed the existence of four other new peptides similar to
      urotoxin. Computer modeling of urotoxin's three-dimensional structure suggests
      the presence of the alpha/beta-scaffold characteristic of other scorpion toxins,
      although very likely forming an uncommon disulfide pairing pattern. Using
      molecular dynamics, a model for the binding of this peptide to human Kv1.2 and
      hKv1.1 channels is presented, along with the binding of an in silico mutant
      urotoxin (Lys25Ala) to both channels. Urotoxin enriches our knowledge of K(+)
      channel toxins and, due to its high affinity for hKv1.2 channels, it may be a
      good candidate for the development of pharmacologic tools to study the
      physiologic functions of K(+) channels or related channelopathies and for
      restoring axonal conduction in demyelinated axons. 

PMID- 24723492
TI  - The physical association of the P2Y12 receptor with PAR4 regulates arrestin
      mediated Akt activation.
AB  - It is now well accepted that protease activated receptor (PAR) 1 and PAR4 have
      differential roles in platelet activation. PAR4, a low-affinity thrombin receptor
      in human platelets, participates in sustained platelet activation in a P2Y12
      dependent manner; however, the mechanisms are not defined. Our previous studies
      demonstrated that thrombin induces the association of PAR4 with P2Y12, together
      with arrestin recruitment to the complex. Here we show that PAR4 and P2Y12
      directly interact to coregulate Akt signaling after PAR4 activation. We observed
      direct and specific interaction of P2Y12 with PAR4 but not PAR1 by bioluminescent
      resonance energy transfer when the receptors were coexpressed in human embryonic
      kidney 293T cells. PAR4-P2Y12 dimerization was promoted by PAR4-AP and inhibited
      by P2Y12 antagonist. By using sequence comparison of the transmembrane domains of
      PAR1 and PAR4, we designed a mutant form of PAR4, "PAR4SFT," by replacing LGL194
      196 at the base of transmembrane domain 4 with the corresponding aligned PAR1
      residues SFT 220-222. PAR4SFT supported only 8.74% of PAR4-P2Y12 interaction,
      abolishing P2Y12-dependent arrestin recruitment to PAR4 and Akt activation.
      Nonetheless, PAR4SFT still supported homodimerization with PAR4. PAR4SFT failed
      to induce a calcium flux when expressed independently; however, coexpression of
      increasing concentrations of PAR4SFT, together with PAR4 potentiated PAR4
      mediated calcium flux, suggested that PAR4 act as homodimers to signal to Gq
      coupled calcium responses. In conclusion, PAR4 LGL (194-196) governs agonist
      dependent association of PAR4 with P2Y12 and contributes to Gq-coupled calcium
      responses. PAR4-P2Y12 association supports arrestin-mediated sustained signaling
      to Akt. Hence, PAR4-P2Y12 dimerization is likely to be important for the PAR4
      P2Y12 dependent stabilization of platelet thrombi. 

PMID- 24723495
TI  - A Bayesian approach to functional mixed-effects modeling for longitudinal data
      with binomial outcomes.
AB  - Longitudinal growth patterns are routinely seen in medical studies where
      individual growth and population growth are followed up over a period of time.
      Many current methods for modeling growth presuppose a parametric relationship
      between the outcome and time (e.g., linear and quadratic); however, these
      relationships may not accurately capture growth over time. Functional mixed
      effects (FME) models provide flexibility in handling longitudinal data with
      nonparametric temporal trends. Although FME methods are well developed for
      continuous, normally distributed outcome measures, nonparametric methods for
      handling categorical outcomes are limited. We consider the situation with
      binomially distributed longitudinal outcomes. Although percent correct data can
      be modeled assuming normality, estimates outside the parameter space are
      possible, and thus, estimated curves can be unrealistic. We propose a binomial
      FME model using Bayesian methodology to account for growth curves with binomial
      (percentage) outcomes. The usefulness of our methods is demonstrated using a
      longitudinal study of speech perception outcomes from cochlear implant users
      where we successfully model both the population and individual growth
      trajectories. Simulation studies also advocate the usefulness of the binomial
      model particularly when outcomes occur near the boundary of the probability
      parameter space and in situations with a small number of trials.

PMID- 24723494
TI  - Proteomic profiling and characterization of differential allergens in the
      nematodes Anisakis simplex sensu stricto and A. pegreffii.
AB  - The parasite species complex Anisakis simplex sensu lato (Anisakis simplex sensu
      stricto; (A. simplex s.s.), A. pegreffii, A. simplex C) is the main cause of
      severe anisakiasis (allergy) worldwide and is now an important health matter. In
      this study, the relationship of this Anisakis species complex and their
      allergenic capacities is assessed by studying the differences between the two
      most frequent species (A. simplex s.s., A. pegreffii) and their hybrid haplotype
      by studying active L3 larvae parasiting Merluccius merluccius. They were compared
      by 2D gel electrophoresis and parallel Western blot (2DE gels were hybridized
      with pools of sera from Anisakis allergenic patients). Unambiguous spot
      differences were detected and protein assignation was made by MALDI-TOF/TOF
      analysis or de novo sequencing. Seventy-five gel spots were detected and the
      corresponding proteins were identified. Differentially expressed proteins for A.
      simplex s.s., A. pegreffii, and their hybrid are described and results are
      statistically supported. Twenty-eight different allergenic proteins are
      classified according to different families belonging to different biological
      functions. These proteins are described for the first time as antigenic and
      potentially new allergens in Anisakis. Comparative proteomic analyses of
      allergenic capacities are useful for diagnosis, epidemiological surveys, and
      clinical research. All MS data have been deposited in the ProteomeXchange with
      identifier PXD000662
      (http://proteomecentral.proteomexchange.org/dataset/PXD000662). 

PMID- 24723497
TI  - Quality improvement informed by a reporting and learning system.

PMID- 24723496
TI  - Cytomorphology of non-small cell lung carcinoma with anaplastic lymphoma kinase
      gene rearrangement.
AB  - Anaplastic lymphoma kinase (ALK) is a receptor tyrosine kinase demonstrating
      activating mutations in several malignancies including a subset (1-5%) of non
      small cell lung carcinomas (NSCLC). Prior work examining, the histologic features
      of these tumors found a spectrum of findings, notably a solid/acinar pattern, as
      well as a mucinous cribriform pattern. We present the first study to date
      describing the cytomorphology of NSCLC harboring ALK rearrangements. A
      retrospective database search was conducted to identify cytologic specimens of
      NSCLC demonstrating ALK rearrangement. Cytogenetic analysis was performed with
      fluorescence in situ hybridization. A total of 12 patients were identified, 10
      with available material. Cellular morphology and smear background was evaluated
      in the study group, as well as control cases lacking ALK rearrangement. A total
      of 25 specimens from 10 patients were obtained. Five patients never smoked, and
      four patients had a remote smoking history. ALK rearrangements were identified in
      cells with unique cytologic characteristics. All cases demonstrated moderate to
      poor differentiation with a predominance of single cells showing anisonucleosis
      and frequent intracytoplasmic neutrophils. The control cases showed cells with
      smaller, less pleomorphic nuclei, and smaller nucleoli with more clusters/tissue
      fragments. Several unique cytomorphologic features were consistently identified
      in the study population relative to the control population and include a
      prominence of single, markedly enlarged tumor cells with plasmacytoid features
      and anisonucleosis, as well as intracytoplasmic neutrophils. Larger studies are
      warranted to confirm our preliminary findings, as these features may help
      establish a more cost-effective means to select patients being tested for ALK
      mutational analysis.

PMID- 24723493
TI  - Chemoimmunotherapy for relapsed/refractory and progressive 17p13-deleted chronic
      lymphocytic leukemia (CLL) combining pentostatin, alemtuzumab, and low-dose
      rituximab is effective and tolerable and limits loss of CD20 expression by
      circulating CLL cells.
AB  - Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL) patients with
      purine analog refractory disease or TP53 dysfunction still have limited treatment
      options and poor survival. Alemtuzumab-containing chemoimmunotherapy regimens can
      be effective but frequently cause serious infections. We report a Phase II trial
      testing the efficacy and tolerability of a short-duration regimen combining
      pentostatin, alemtuzumab, and low-dose high-frequency rituximab designed to
      decrease the risk of treatment-associated infections and to limit the loss of
      CD20 expression by CLL cells. The study enrolled 39 patients with progressive CLL
      that was either relapsed/refractory (n = 36) or previously untreated with 17p13
      deletion (17p13-) (n = 3). Thirteen (33%) patients had both 17p13- and TP53
      mutations predicted to be dysfunctional, and eight patients had purine analog
      refractory CLL without TP53 dysfunction. Twenty-six (67%) patients completed
      therapy, with only five (13%) patients having treatment-limiting toxicity and no
      treatment-related deaths. Twenty-two (56%) patients responded to treatment, with
      11 (28%) complete responses (four with incomplete bone marrow recovery). Median
      progression-free survival was 7.2 months, time to next treatment was 9.1 months,
      and overall survival was 34.1 months. The majority of deaths (82%) were caused by
      progressive disease, including transformed diffuse large B-cell lymphoma (n = 6).
      Correlative studies showed that low-dose rituximab activates complement and
      natural killer cells without a profound and sustained decrease in expression of
      CD20 by circulating CLL cells. We conclude that pentostatin, alemtuzumab, and low
      dose high-frequency rituximab is a tolerable and effective therapy for CLL and
      that low-dose rituximab therapy can activate innate immune cytotoxic mechanisms
      without substantially decreasing CD20 expression.

PMID- 24723498
TI  - Cardio-adipose tissue cross-talk: relationship between adiponectin, plasma pro
      brain natriuretic peptide and incident heart failure.
AB  - AIMS: There is increasing evidence of cross-talk between the heart, body
      metabolism, and adipose tissue, but the precise mechanisms are poorly understood.
      Natriuretic peptides (NPs) have recently emerged as the prime candidate for a
      mediator. In patients with heart failure (HF), infusion of NPs increases
      adiponectin secretion, indicating that NPs may improve adipose tissue function
      and in this way function as a cardio-protective agent in HF. Accordingly we
      investigated the interplay between plasma adiponectin, plasma proBNP, and
      development of HF. METHODS AND RESULTS: We prospectively followed 5574 randomly
      selected men and women from the community without ischaemic heart disease or HF.
      Plasma adiponectin and proBNP were measured at study entry. Median follow-up time
      was 8.5 years (interquartile range 8.0-9.1 years). During follow-up 271
      participants developed symptomatic HF. Plasma adiponectin and proBNP were
      strongly associated (P < 0.001). Participants with increasing adiponectin had
      increased risk of incident HF (P < 0.001). After adjustment for confounding risk
      factors (including age, gender, smoking status, body mass ratio, waist-hip ratio,
      glucose, glycated haemoglobin, systolic and diastolic blood pressure, lipid
      profile, high sensitivity C-reactive protein, estimated glomerular filtration
      rate, and physical activity) by Cox regression analysis, adiponectin remained an
      independent predictor of HF: the hazard ratio (HR) per 1 standard deviation (SD)
      increase in adiponectin was 1.20 [95% confidence interval (CI) 1.06-1.30; P =
      0.003]. However, the association vanished when plasma proBNP was included in the
      analysis, HR 1.08 (95% CI 0.95-1.23; P = 0.26). CONCLUSIONS: In conclusion,
      plasma adiponectin and proBNP are strongly associated. Increasing plasma
      adiponectin is associated with increased risk of HF. However, concomitantly
      elevated proBNP levels appear to explain the positive association between
      adiponectin and risk of HF.

PMID- 24723500
TI  - Mechanisms of kidney repair by human mesenchymal stromal cells after ischemia: a
      comprehensive view using label-free MS(E).
AB  - Acute kidney injury (AKI) is one of the more frequent and lethal pathological
      conditions seen in intensive care units. Currently available treatments are not
      totally effective but stem cell-based therapies are emerging as promising
      alternatives, especially the use of mesenchymal stromal cells (MSC), although the
      signaling pathways involved in their beneficial actions are not fully understood.
      The objective of this study was to identify signaling networks and key proteins
      involved in the repair of ischemia by MSC. Using an in vitro model of AKI to
      investigate paracrine interactions and label-free high definition 2D-NanoESI
      MS(E) , differentially expressed proteins were identified in a human renal
      proximal tubule cell lineage (HK-2) exposed to human MSC (hMSC) after an ischemic
      insult. In silico analysis showed that hMSC stimulated antiapoptotic activity,
      normal ROS handling, energy production, cytoskeleton organization, protein
      synthesis, and cell proliferation. The proteomic data were validated by parallel
      experiments demonstrating reduced apoptosis in HK-2 cells and recovery of
      intracellular ATP levels. qRT-PCR for proteins implicated in the above processes
      revealed that hMSC exerted their effects by stimulating translation, not
      transcription. Western blotting of proteins associated with ROS and energy
      metabolism confirmed their higher abundance in HK-2 cells exposed to hMSC. 

PMID- 24723501
TI  - Evaluation of femoral perfusion in a rabbit model of steroid-induced
      osteonecrosis by dynamic contrast-enhanced MRI with a high magnetic field MRI
      system.
AB  - PURPOSE: To evaluate perfusion during the early phase after steroid
      administration in vivo using dynamic contrast-enhanced magnetic resonance imaging
      (DCE-MRI) with a high magnetic field MRI system. The main pathogenesis of steroid
      induced osteonecrosis is considered to be ischemia. MATERIALS AND METHODS: A
      single dose of methylprednisolone (MPSL) was injected into nine rabbits. DCE-MRI
      was performed for these rabbits before MPSL administration and 1, 5, 10, and 14
      days after administration. Time-signal intensity curves were created for each
      femur based on the signal intensity to evaluate perfusion. Enhancement ratio
      (ER), initial slope (IS), and area under the curve (AUC) were calculated and the
      value before MPSL administration and the minimal value after administration were
      compared statistically. RESULTS: ER, IS, and AUC values after MPSL administration
      significantly decreased (P < 0.05, P < 0.01, and P < 0.01, respectively). All of
      them decreased by the 5th day in 56% of the femora and by the 14th day in 83%,
      and some femora even showed a decrease from the 1st day. CONCLUSION: In this
      study, decreased perfusion in the femora after steroid administration was proven.
      Additionally, we could show that it occurred from the early days after steroid
      administration.

PMID- 24723502
TI  - Effect of deletion and overexpression of tryptophan metabolism genes on growth
      and fermentation capacity at low temperature in wine yeast.
AB  - Low-temperature fermentations produce wines with greater aromatic complexity, but
      the success of these fermentations greatly depends on the adaptation of yeast
      cells to cold. Tryptophan has been previously reported to be a limiting amino
      acid during Saccharomyces cerevisiae growth at low temperature. The objective of
      this study was to determine the influence of the tryptophan metabolism on growth
      and fermentation performance during low-temperature wine fermentation. To this
      end, we constructed the deletion mutants of the TRP1 and TAT2 genes in a
      derivative haploid of a commercial wine strain, and the TAT2 gene was
      overexpressed in the prototroph and auxotroph (Deltatrp1) backgrounds. Then we
      characterized growth and fermentation activity during wine fermentation at low
      and optimum temperatures. Our results partially support the role of this amino
      acid in cold yeast growth. Although deletion of TRP1 impaired amino acid uptake
      and the growth rate at low temperature in synthetic must, this growth impairment
      did not affect the fermentation rate. Deletion of TAT2 endorsed this strain with
      the highest nitrogen consumption capacity and the greatest fermentation activity
      at low temperature. Our results also evidenced reduced ammonium consumption in
      all the strains at low temperature.

PMID- 24723503
TI  - Etiology and mortality of spontaneous bacterial peritonitis in liver transplant
      recipients: a cohort study.
AB  - Spontaneous bacterial peritonitis (SBP) in liver transplantation (LT) recipients
      who progress to cirrhosis has received little attention. We investigated the
      adequacy of empirical treatment with third-generation cephalosporins for SBP in
      this population and the impact of transplantation on the evolution of the
      infection. We performed a cohort study with 138 SBP episodes: 19 in LT patients
      and 119 in non-LT patients. The etiology of SBP was identified for 73.7% of the
      episodes in LT patients and for 38.7% of the episodes in non-LT patients (P =
      0.004). The main microorganisms in recipients were Escherichia coli (35.7%) and
      Streptococcus pneumoniae (21.4%). The etiologies did not differ in non-LT
      patients. The cephalosporin sensitivity was similar in the 2 groups (85.7% versus
      78.4%, P = 0.7). LT recipients developed renal failure (57.9% versus 25.2%, P =
      0.004) and encephalopathy (42.1% versus 22%, P = 0.08) more often than non-LT
      patients, and the mortality rates during episodes (52.6% versus 13.4%, P < 0.001)
      and at 6 months (70.6% versus 34.7%, P = 0.005) were higher. According to a
      multivariate analysis, the mortality-associated risk factors at diagnosis were a
      Model for End-Stage Liver Disease (MELD) score > 18 odds ratio (OR) = 6.1 and
      being an LT recipient (OR = 4.45). At 6 months, the risk factors for mortality
      were a MELD score > 18 (OR = 3.08), being an LT recipient (OR = 3.47), a known
      etiology (OR = 2.08), and the presence of hepatocellular carcinoma (OR = 3.73).

PMID- 24723504
TI  - A new bifunctional chelator enables facile biocoupling and radiolabeling as the
      basis for a bioconjugation kit.
AB  - A new tridentate bifunctional chelator, N-(-2-picolyl)(-4-hydroxy)(-3
      amino)benzoic acid (PHAB), was designed to efficiently coordinate the
      [(99m)Tc(CO)3](+) core and facilitate coupling reactions to biomolecules. The
      chelator can be procured in the form of the corresponding benzotriazole ester
      (PHAB-OBT), which can be stored and used as a bioconjugation kit. PHAB-OBT reacts
      with modified carbohydrates with high selectivity and efficiency in a single step
      in both aqueous and organic media. As is desirable for a kit, no complicated
      chemical bench work is required. Glycoconjugate postlabeling resulted in neutral
      radiolabeled glycans with high radiochemical yields. Prelabeling approaches were
      assessed by successive reaction of PHAB-OBT with the [(99m)Tc(CO)3](+) core and a
      modified galactose model. The radiolabeled galactose was obtained in 84% yield as
      defined by HPLC analysis. Biodistribution of the radioactive (99m)Tc-labeled
      chelator, as well as the glycoconjugates, were examined in mice. Noticeably
      different biodistribution patterns were observed that reflect trends in the
      uptake of carbohydrate analogues by various organs.

PMID- 24723505
TI  - GOAT--a simple LC-MS/MS gradient optimization tool.
AB  - Modern nano-HPLC systems are capable of extremely precise control of solvent
      gradients, allowing high-resolution separation of peptides. Most proteomics
      laboratories use a simple linear analytical gradient for nano-LC-MS/MS
      experiments, though recent evidence indicates that optimized non-linear gradients
      result in increased peptide and protein identifications from cell lysates. In
      concurrent work, we examined non-linear gradients for the analysis of samples
      fractionated at the peptide level, where the distribution of peptide retention
      times often varies by fraction. We hypothesized that greater coverage of these
      samples could be achieved using per-fraction optimized gradients. We demonstrate
      that the optimized gradients improve the distribution of peptides throughout the
      analysis. Using previous generation MS instrumentation, a considerable gain in
      peptide and protein identifications can be realized. With current MS platforms
      that have faster electronics and achieve shorter duty cycle, the improvement in
      identifications is smaller. Our gradient optimization method has been implemented
      in a simple graphical tool (GOAT) that is MS-vendor independent, does not require
      peptide ID input, and is freely available for non-commercial use at
      http://proteomics.swmed.edu/goat/ 

PMID- 24723506
TI  - Gender-intrusive questioning: a survey of expert witnesses.
AB  - This paper reports the results of a survey of male and female psychologists with
      expert witness experience. The survey explored the roles of both expert witness
      gender and valence of the testimony to provide preliminary empirical data on
      whether gender in combination with the valence of testimony leads to perceived
      bias targeted towards female experts. The presence of such bias might diminish
      the credibility of the expert and subsequently the proffered testimony and, thus,
      undermine the legal system as effective fact-finder by leading to decision-making
      based on extra-legal factors.

PMID- 24723507
TI  - Can serial rapists be distinguished from one-off rapists?
AB  - There are investigative advantages to being able to determine early in a police
      investigation whether a rape has been committed by a serial or a one-off rapist.
      Previous research has found some differences in the crime-scene behaviors of
      serial and one-off rapists; however, this research suffers from the limitation of
      utilizing a sample of rapes within which there was a mixture of victim-offender
      relationships. To address this limitation, this study sampled 38 serial (two or
      more convictions) and 50 one-off (one conviction) stranger rapists and compared
      their crime scene behavior across four domains (control, sex, escape and style
      behaviors). Serial and one-off rapists differed in some control and sexual
      behaviors, in particular, in the type of victim targeted, the offense locations,
      methods of control and the sexual acts forced upon the victim. However, the
      results did not indicate a striking difference in the offending behavior of the
      two groups. The implications of these findings for criminal investigations are
      discussed.

PMID- 24723508
TI  - Practical methods for improving B1+ homogeneity in 3 Tesla breast imaging.
AB  - PURPOSE: To improve image contrast and B1+ field homogeneity in 3 Tesla (T)
      breast MR. MATERIALS AND METHODS: Two practical B1+ shimming methods for 3T
      breast MR are presented; low-cost passive shimming using local pads of high
      dielectric permittivity (epsilonr from 0 to 100), and two-channel radiofrequency
      (RF) shimming (adjusting Q-I amplitude ratios and phase differences of 0 to -4 dB
      and 90 to 45 degrees), as well as a combination of both methods. The technique
      has been studied both in simulation using a numerical body model with added
      mammary tissue and in vivo in six subjects. RESULTS: Large improvements are
      observed with both methods, leading to a decrease in left-right B1+ asymmetry
      ratio of 1.24 to 1.00 (simulation) and from 1.26 to 1.01 (in vivo). RF safety was
      not adversely affected. CONCLUSION: Both RF shimming and dielectric shimming were
      shown to improve inhomogeneity in the B1+ field in 3T breast MR.

PMID- 24723513
TI  - The Nozoe Autograph Books: segment 10.

PMID- 24723509
TI  - Refolding and purification of recombinant human (Pro)renin receptor from
      Escherichia coli by ion exchange chromatography.
AB  - Purification of the recombinant human renin receptor (rhRnR) is a major aspect of
      its biological or biophysical analysis, as well as structural research. A simple
      and efficient method for the refolding and purification of rhRnR expressed in
      Escherichia coli with weak anion-exchange chromatography (WAX) was presented in
      this work. The solution containing denatured rhRnR in 8.0 mol/L urea extracted
      from the inclusion bodies was directly injected into the WAX column. The
      aggregation was prevented and the soluble form of renatured rhRnR in aqueous
      solution was obtained after desorption from the column. Effects of the extracting
      solutions, the pH values and urea concentrations in the mobile phase, as well as
      the sample size on the refolding and purification of rhRnR were investigated,
      indicating that the above mentioned factors had remarkable influences on the
      efficiency of refolding, purification and mass recovery of rhRnR. Under the
      optimal conditions, rhRnR was successfully refolded and purified simultaneously
      by WAX in one step within only 30 min. The result was satisfactory with mass
      recovery of 71.8% and purity of 94.8%, which was further tested by western
      blotting. The specific binding of the purified rhRnR to recombinant human renin
      was also determined using surface plasmon resonance (SPR). The association
      constant of rhRnR to recombinant human renin was calculated to be 3.25 * 10(8)
      L/mol, which demonstrated that rhRnR was already renatured and simultaneously
      purified in one step using WAX. All of the above demonstrate that protein folding
      liquid chromatography (PFLC) should be a powerful tool for the purification and
      renaturation of rhRnR.

PMID- 24723514
TI  - A novel "continuous-interrupted" method for microvascular anastomosis.

PMID- 24723515
TI  - Hydrophilic polydopamine-coated magnetic graphene nanocomposites for highly
      efficient tryptic immobilization.
AB  - In this work, polydopamine-coated magnetic graphene (MG@PDA) nanocomposites were
      synthesized by a facile method. Trypsin was then directly immobilized on the
      surface of the nanocomposites through simple PDA chemistry with no need for
      introducing any other coupling groups. The as-made MG@PDA nanocomposites inherit
      not only the large surface area of graphene which makes them capable of
      immobilizing high amount of trypsin (up to 0.175 mg/mg), but also the good
      hydrophilicity of PDA which greatly improves their biocompatibility. Moreover,
      the strong magnetic responsibility makes them easy to be separated from the
      digested peptide solution when applying a magnetic field. The feasibility of the
      trypsin-immobilized MG@PDA (MG@PDA-trypsin) nanocomposites for protein digestion
      was investigated and the results indicated their high digestion efficiency in a
      short digestion time (10 min). In addition, the reusability and stability of the
      MG@PDA-trypsin nanocomposites were also tested in our work. To further confirm
      the efficiency of MG@PDA-trypsin nanocomposites for proteome analysis, they were
      applied to digest proteins extracted from skimmed milk, followed by nano RPLC-ESI
      MS/MS analysis, and a total of 321 proteins were identified, much more than those
      obtained by 16-h in-solution digestion (264 proteins), indicating the great
      potential of MG@PDA-trypsin nanocomposites as the supports for high-throughput
      proteome study. 

PMID- 24723516
TI  - Image interpolation via graph-based Bayesian label propagation.
AB  - In this paper, we propose a novel image interpolation algorithm via graph-based
      Bayesian label propagation. The basic idea is to first create a graph with known
      and unknown pixels as vertices and with edge weights encoding the similarity
      between vertices, then the problem of interpolation converts to how to
      effectively propagate the label information from known points to unknown ones.
      This process can be posed as a Bayesian inference, in which we try to combine the
      principles of local adaptation and global consistency to obtain accurate and
      robust estimation. Specially, our algorithm first constructs a set of local
      interpolation models, which predict the intensity labels of all image samples,
      and a loss term will be minimized to keep the predicted labels of the available
      low-resolution (LR) samples sufficiently close to the original ones. Then, all of
      the losses evaluated in local neighborhoods are accumulated together to measure
      the global consistency on all samples. Moreover, a graph-Laplacian-based manifold
      regularization term is incorporated to penalize the global smoothness of
      intensity labels, such smoothing can alleviate the insufficient training of the
      local models and make them more robust. Finally, we construct a unified objective
      function to combine together the global loss of the locally linear regression,
      square error of prediction bias on the available LR samples, and the manifold
      regularization term. It can be solved with a closed-form solution as a convex
      optimization problem. Experimental results demonstrate that the proposed method
      achieves competitive performance with the state-of-the-art image interpolation
      algorithms. 

PMID- 24723517
TI  - Robust face recognition from multi-view videos.
AB  - Multiview face recognition has become an active research area in the last few
      years. In this paper, we present an approach for video-based face recognition in
      camera networks. Our goal is to handle pose variations by exploiting the
      redundancy in the multiview video data. However, unlike traditional approaches
      that explicitly estimate the pose of the face, we propose a novel feature for
      robust face recognition in the presence of diffuse lighting and pose variations.
      The proposed feature is developed using the spherical harmonic representation of
      the face texture-mapped onto a sphere; the texture map itself is generated by
      back-projecting the multiview video data. Video plays an important role in this
      scenario. First, it provides an automatic and efficient way for feature
      extraction. Second, the data redundancy renders the recognition algorithm more
      robust. We measure the similarity between feature sets from different videos
      using the reproducing kernel Hilbert space. We demonstrate that the proposed
      approach outperforms traditional algorithms on a multiview video database. 

PMID- 24723518
TI  - Cartoon-texture image decomposition using blockwise low-rank texture
      characterization.
AB  - Using a novel characterization of texture, we propose an image decomposition
      technique that can effectively decomposes an image into its cartoon and texture
      components. The characterization rests on our observation that the texture
      component enjoys a blockwise low-rank nature with possible overlap and shear,
      because texture, in general, is globally dissimilar but locally well patterned.
      More specifically, one can observe that any local block of the texture component
      consists of only a few individual patterns. Based on this premise, we first
      introduce a new convex prior, named the block nuclear norm (BNN), leading to a
      suitable characterization of the texture component. We then formulate a cartoon
      texture decomposition model as a convex optimization problem, where the
      simultaneous estimation of the cartoon and texture components from a given image
      or degraded observation is executed by minimizing the total variation and BNN. In
      addition, patterns of texture extending in different directions are extracted
      separately, which is a special feature of the proposed model and of benefit to
      texture analysis and other applications. Furthermore, the model can handle
      various types of degradation occurring in image processing, including
      blur+missing pixels with several types of noise. By rewriting the problem via
      variable splitting, the so-called alternating direction method of multipliers
      becomes applicable, resulting in an efficient algorithmic solution to the
      problem. Numerical examples illustrate that the proposed model is very selective
      to patterns of texture, which makes it produce better results than state-of-the
      art decomposition models. 

PMID- 24723519
TI  - Convex-relaxed kernel mapping for image segmentation.
AB  - This paper investigates a convex-relaxed kernel mapping formulation of image
      segmentation. We optimize, under some partition constraints, a functional
      containing two characteristic terms: 1) a data term, which maps the observation
      space to a higher (possibly infinite) dimensional feature space via a kernel
      function, thereby evaluating nonlinear distances between the observations and
      segments parameters and 2) a total-variation term, which favors smooth segment
      surfaces (or boundaries). The algorithm iterates two steps: 1) a convex
      relaxation optimization with respect to the segments by solving an equivalent
      constrained problem via the augmented Lagrange multiplier method and 2) a
      convergent fixed-point optimization with respect to the segments parameters. The
      proposed algorithm can bear with a variety of image types without the need for
      complex and application-specific statistical modeling, while having the
      computational benefits of convex relaxation. Our solution is amenable to
      parallelized implementations on graphics processing units (GPUs) and extends
      easily to high dimensions. We evaluated the proposed algorithm with several sets
      of comprehensive experiments and comparisons, including: 1) computational
      evaluations over 3D medical-imaging examples and high-resolution large-size color
      photographs, which demonstrate that a parallelized implementation of the proposed
      method run on a GPU can bring a significant speed-up and 2) accuracy evaluations
      against five state-of-the-art methods over the Berkeley color-image database and
      a multimodel synthetic data set, which demonstrates competitive performances of
      the algorithm. 

PMID- 24723520
TI  - Joint non-Gaussian denoising and superresolving of raw high frame rate videos.
AB  - High frame rate cameras capture sharp videos of highly dynamic scenes by trading
      off signal-noise-ratio and image resolution, so combinational super-resolving and
      denoising is crucial for enhancing high speed videos and extending their
      applications. The solution is nontrivial due to the fact that two deteriorations
      co-occur during capturing and noise is nonlinearly dependent on signal strength.
      To handle this problem, we propose conducting noise separation and super
      resolution under a unified optimization framework, which models both
      spatiotemporal priors of high quality videos and signal-dependent noise.
      Mathematically, we align the frames along temporal axis and pursue the solution
      under the following three criterion: 1) the sharp noise-free image stack is low
      rank with some missing pixels denoting occlusions; 2) the noise follows a given
      nonlinear noise model; and 3) the recovered sharp image can be reconstructed well
      with sparse coefficients and an over complete dictionary learned from high
      quality natural images. In computation aspects, we propose to obtain the final
      result by solving a convex optimization using the modern local linearization
      techniques. In the experiments, we validate the proposed approach in both
      synthetic and real captured data. 

PMID- 24723521
TI  - Does deblurring improve geometrical hyperspectral unmixing?
AB  - In this paper, we consider hyperspectral unmixing problems where the observed
      images are blurred during the acquisition process, e.g., in microscopy and
      spectroscopy. We derive a joint observation and mixing model and show how it
      affects end-member identifiability within the geometrical unmixing framework. An
      analysis of the model reveals that nonnegative blurring results in a contraction
      of both the minimum-volume enclosing and maximum-volume enclosed simplex. We
      demonstrate this contraction property in the case of a spectrally invariant point
      spread function. The benefit of prior deconvolution on the accuracy of the
      restored sources and abundances is illustrated using simulated and real Raman
      spectroscopic data. 

PMID- 24723522
TI  - Super-resolution for computed tomography based on discrete tomography.
AB  - In computed tomography (CT), partial volume effects impede accurate segmentation
      of structures that are small with respect to the pixel size. In this paper, it is
      shown that for objects consisting of a small number of homogeneous materials, the
      reconstruction resolution can be substantially increased without altering the
      acquisition process. A super-resolution reconstruction approach is introduced
      that is based on discrete tomography, in which prior knowledge about the
      materials in the object is assumed. Discrete tomography has already been used to
      create reconstructions from a low number of projection angles, but in this paper,
      it is demonstrated that it can also be applied to increase the reconstruction
      resolution. Experiments on simulated and real MUCT data of bone and foam
      structures show that the proposed method indeed leads to significantly improved
      structure segmentation and quantification compared with what can be achieved from
      conventional reconstructions. 

PMID- 24723523
TI  - An unsupervised feature selection dynamic mixture model for motion segmentation.
AB  - The automatic clustering of time-varying characteristics and phenomena in natural
      scenes has recently received great attention. While there exist many algorithms
      for motion segmentation, an important issue arising from these studies concerns
      that for which attributes of the data should be used to cluster phenomena with a
      certain repetitiveness in both space and time. It is difficult because there is
      no knowledge about the labels of the phenomena to guide the search. In this
      paper, we present a feature selection dynamic mixture model for motion
      segmentation. The advantage of our method is that it is intuitively appealing,
      avoiding any combinatorial search, and allowing us to prune the feature set.
      Numerical experiments on various phenomena are conducted. The performance of the
      proposed model is compared with that of other motion segmentation algorithms,
      demonstrating the robustness and accuracy of our method. 

PMID- 24723524
TI  - Quadtree structured image approximation for denoising and interpolation.
AB  - The success of many image restoration algorithms is often due to their ability to
      sparsely describe the original signal. Shukla proposed a compression algorithm,
      based on a sparse quadtree decomposition model, which could optimally represent
      piecewise polynomial images. In this paper, we adapt this model to the image
      restoration by changing the rate-distortion penalty to a description-length
      penalty. In addition, one of the major drawbacks of this type of approximation is
      the computational complexity required to find a suitable subspace for each node
      of the quadtree. We address this issue by searching for a suitable subspace much
      more efficiently using the mathematics of updating matrix factorisations.
      Algorithms are developed to tackle denoising and interpolation. Simulation
      results indicate that we beat state of the art results when the original signal
      is in the model (e.g., depth images) and are competitive for natural images when
      the degradation is high. 

PMID- 24723525
TI  - Robust automatic line scratch detection in films.
AB  - Line scratch detection in old films is a particularly challenging problem due to
      the variable spatiotemporal characteristics of this defect. Some of the main
      problems include sensitivity to noise and texture, and false detections due to
      thin vertical structures belonging to the scene. We propose a robust and
      automatic algorithm for frame-by-frame line scratch detection in old films, as
      well as a temporal algorithm for the filtering of false detections. In the frame
      by-frame algorithm, we relax some of the hypotheses used in previous algorithms
      in order to detect a wider variety of scratches. This step's robustness and lack
      of external parameters is ensured by the combined use of an a contrario
      methodology and local statistical estimation. In this manner, over-detection in
      textured or cluttered areas is greatly reduced. The temporal filtering algorithm
      eliminates false detections due to thin vertical structures by exploiting the
      coherence of their motion with that of the underlying scene. Experiments
      demonstrate the ability of the resulting detection procedure to deal with
      difficult situations, in particular in the presence of noise, texture, and
      slanted or partial scratches. Comparisons show significant advantages over
      previous work. 

PMID- 24723526
TI  - An unbiased risk estimator for image denoising in the presence of mixed poisson
      gaussian noise.
AB  - The behavior and performance of denoising algorithms are governed by one or
      several parameters, whose optimal settings depend on the content of the processed
      image and the characteristics of the noise, and are generally designed to
      minimize the mean squared error (MSE) between the denoised image returned by the
      algorithm and a virtual ground truth. In this paper, we introduce a new Poisson
      Gaussian unbiased risk estimator (PG-URE) of the MSE applicable to a mixed
      Poisson-Gaussian noise model that unifies the widely used Gaussian and Poisson
      noise models in fluorescence bioimaging applications. We propose a stochastic
      methodology to evaluate this estimator in the case when little is known about the
      internal machinery of the considered denoising algorithm, and we analyze both
      theoretically and empirically the characteristics of the PG-URE estimator.
      Finally, we evaluate the PG-URE-driven parametrization for three standard
      denoising algorithms, with and without variance stabilizing transforms, and
      different characteristics of the Poisson-Gaussian noise mixture. 

PMID- 24723527
TI  - Group-invariant colour morphology based on frames.
AB  - Mathematical morphology is a very popular framework for processing binary or
      grayscale images. One of the key problems in applying this framework to color
      images is the notorious false color problem. We discuss the nature of this
      problem and its origins. In doing so, it becomes apparent that the lack of
      invariance of operators to certain transformations (forming a group) plays an
      important role. The main culprits are the basic join and meet operations, and the
      associated lattice structure that forms the theoretical basis for mathematical
      morphology. We show how a lattice that is not group invariant can be related to
      another lattice that is. When all transformations in a group are linear, these
      lattices can be related to one another via the theory of frames. This provides
      all the machinery to let us transform any (grayscale or color) morphological
      filter into a group-invariant filter on grayscale or color images. We then
      demonstrate the potential for both subjective and objective improvement in
      selected tasks. 

PMID- 24723528
TI  - Transparent composite model for DCT coefficients: design and analysis.
AB  - The distributions of discrete cosine transform (DCT) coefficients of images are
      revisited on a per image base. To better handle, the heavy tail phenomenon
      commonly seen in the DCT coefficients, a new model dubbed a transparent composite
      model (TCM) is proposed and justified for both modeling accuracy and an
      additional data reduction capability. Given a sequence of the DCT coefficients, a
      TCM first separates the tail from the main body of the sequence. Then, a uniform
      distribution is used to model the DCT coefficients in the heavy tail, whereas a
      different parametric distribution is used to model data in the main body. The
      separate boundary and other parameters of the TCM can be estimated via maximum
      likelihood estimation. Efficient online algorithms are proposed for parameter
      estimation and their convergence is also proved. Experimental results based on
      Kullback-Leibler divergence and chi(2) test show that for real-valued continuous
      ac coefficients, the TCM based on truncated Laplacian offers the best tradeoff
      between modeling accuracy and complexity. For discrete or integer DCT
      coefficients, the discrete TCM based on truncated geometric distributions (GMTCM)
      models the ac coefficients more accurately than pure Laplacian models and
      generalized Gaussian models in majority cases while having simplicity and
      practicality similar to those of pure Laplacian models. In addition, it is
      demonstrated that the GMTCM also exhibits a good capability of data reduction or
      feature extraction-the DCT coefficients in the heavy tail identified by the GMTCM
      are truly outliers, and these outliers represent an outlier image revealing some
      unique global features of the image. Overall, the modeling performance and the
      data reduction feature of the GMTCM make it a desirable choice for modeling
      discrete or integer DCT coefficients in the real-world image or video
      applications, as summarized in a few of our further studies on quantization
      design, entropy coding design, and image understanding and management. 

PMID- 24723529
TI  - A compressive sensing based secure watermark detection and privacy preserving
      storage framework.
AB  - Privacy is a critical issue when the data owners outsource data storage or
      processing to a third party computing service, such as the cloud. In this paper,
      we identify a cloud computing application scenario that requires simultaneously
      performing secure watermark detection and privacy preserving multimedia data
      storage. We then propose a compressive sensing (CS)-based framework using secure
      multiparty computation (MPC) protocols to address such a requirement. In our
      framework, the multimedia data and secret watermark pattern are presented to the
      cloud for secure watermark detection in a CS domain to protect the privacy.
      During CS transformation, the privacy of the CS matrix and the watermark pattern
      is protected by the MPC protocols under the semi-honest security model. We derive
      the expected watermark detection performance in the CS domain, given the target
      image, watermark pattern, and the size of the CS matrix (but without the CS
      matrix itself). The correctness of the derived performance has been validated by
      our experiments. Our theoretical analysis and experimental results show that
      secure watermark detection in the CS domain is feasible. Our framework can also
      be extended to other collaborative secure signal processing and data-mining
      applications in the cloud. 

PMID- 24723530
TI  - Noise parameter estimation for poisson corrupted images using variance
      stabilization transforms.
AB  - Noise is present in all images captured by real-world image sensors. Poisson
      distribution is said to model the stochastic nature of the photon arrival process
      and agrees with the distribution of measured pixel values. We propose a method
      for estimating unknown noise parameters from Poisson corrupted images using
      properties of variance stabilization. With a significantly lower computational
      complexity and improved stability, the proposed estimation technique yields noise
      parameters that are comparable in accuracy to the state-of-art methods. 

PMID- 24723532
TI  - Blind prediction of natural video quality.
AB  - We propose a blind (no reference or NR) video quality evaluation model that is
      nondistortion specific. The approach relies on a spatio-temporal model of video
      scenes in the discrete cosine transform domain, and on a model that characterizes
      the type of motion occurring in the scenes, to predict video quality. We use the
      models to define video statistics and perceptual features that are the basis of a
      video quality assessment (VQA) algorithm that does not require the presence of a
      pristine video to compare against in order to predict a perceptual quality score.
      The contributions of this paper are threefold. 1) We propose a spatio-temporal
      natural scene statistics (NSS) model for videos. 2) We propose a motion model
      that quantifies motion coherency in video scenes. 3) We show that the proposed
      NSS and motion coherency models are appropriate for quality assessment of videos,
      and we utilize them to design a blind VQA algorithm that correlates highly with
      human judgments of quality. The proposed algorithm, called video BLIINDS, is
      tested on the LIVE VQA database and on the EPFL-PoliMi video database and shown
      to perform close to the level of top performing reduced and full reference VQA
      algorithms. 

PMID- 24723531
TI  - A complete system for automatic extraction of left ventricular myocardium from CT
      images using shape segmentation and contour evolution.
AB  - The left ventricular myocardium plays a key role in the entire circulation system
      and an automatic delineation of the myocardium is a prerequisite for most of the
      subsequent functional analysis. In this paper, we present a complete system for
      an automatic segmentation of the left ventricular myocardium from cardiac
      computed tomography (CT) images using the shape information from images to be
      segmented. The system follows a coarse-to-fine strategy by first localizing the
      left ventricle and then deforming the myocardial surfaces of the left ventricle
      to refine the segmentation. In particular, the blood pool of a CT image is
      extracted and represented as a triangulated surface. Then, the left ventricle is
      localized as a salient component on this surface using geometric and anatomical
      characteristics. After that, the myocardial surfaces are initialized from the
      localization result and evolved by applying forces from the image intensities
      with a constraint based on the initial myocardial surface locations. The proposed
      framework has been validated on 34-human and 12-pig CT images, and the robustness
      and accuracy are demonstrated. 

PMID- 24723533
TI  - Color-image quality assessment: from prediction to optimization.
AB  - While image-difference metrics show good prediction performance on visual data,
      they often yield artifact-contaminated results if used as objective functions for
      optimizing complex image-processing tasks. We investigate in this regard the
      recently proposed color-image-difference (CID) metric particularly developed for
      predicting gamut-mapping distortions. We present an algorithm for optimizing
      gamut mapping employing the CID metric as the objective function. Resulting
      images contain various visual artifacts, which are addressed by multiple
      modifications yielding the improved color-image-difference (iCID) metric. The
      iCID-based optimizations are free from artifacts and retain contrast, structure,
      and color of the original image to a great extent. Furthermore, the prediction
      performance on visual data is improved by the modifications. 

PMID- 24723534
TI  - Accelerated nonlinear multichannel ultrasonic tomographic imaging using target
      sparseness.
AB  - This paper presents an accelerated iterative Landweber method for nonlinear
      ultrasonic tomographic imaging in a multiple-input multiple-output (MIMO)
      configuration under a sparsity constraint on the image. The proposed method
      introduces the emerging MIMO signal processing techniques and target sparseness
      constraints in the traditional computational imaging field, thus significantly
      improves the speed of image reconstruction compared with the conventional imaging
      method while producing high quality images. Using numerical examples, we
      demonstrate that incorporating prior knowledge about the imaging field such as
      target sparseness accelerates significantly the convergence of the iterative
      imaging method, which provides considerable benefits to real-time tomographic
      imaging applications. 

PMID- 24723535
TI  - Robust estimation of motion blur kernel using a piecewise-linear model.
AB  - Blur kernel estimation is a crucial step in the deblurring process for images.
      Estimation of the kernel, especially in the presence of noise, is easily
      perturbed, and the quality of the resulting deblurred images is hence degraded.
      Since every motion blur in a single exposure image can be represented by 2D
      parametric curves, we adopt a piecewise-linear model to approximate the curves
      for the reliable blur kernel estimation. The model is found to be an effective
      tradeoff between flexibility and robustness as it takes advantage of two
      extremes: (1) the generic model, represented by a discrete 2D function, which has
      a high degree of freedom (DOF) for the maximum flexibility but suffers from noise
      and (2) the linear model, which enhances robustness and simplicity but has
      limited expressiveness due to its low DOF. We evaluate several deblurring methods
      based on not only the generic model, but also the piecewise-linear model as an
      alternative. After analyzing the experiment results using real-world images with
      significant levels of noise and a benchmark data set, we conclude that the
      proposed model is not only robust with respect to noise, but also flexible in
      dealing with various types of blur. 

PMID- 24723536
TI  - Common Visual Pattern Discovery via Directed Graph.
AB  - A directed graph (or digraph) approach is proposed in this paper for identifying
      all the visual objects commonly presented in the two images under comparison. As
      a model, the directed graph is superior to the undirected graph, since there are
      two link weights with opposite orientations associated with each link of the
      graph. However, it inevitably draws two main challenges: 1) how to compute the
      two link weights for each link and 2) how to extract the subgraph from the
      digraph. For 1), a novel n-ranking process for computing the generalized median
      and the Gaussian link-weight mapping function are developed that basically map
      the established undirected graph to the digraph. To achieve this graph mapping,
      the proposed process and function are applied to each vertex independently for
      computing its directed link weight by not only considering the influences
      inserted from its immediately adjacent neighboring vertices (in terms of their
      link-weight values), but also offering other desirable merits-i.e., link-weight
      enhancement and computational complexity reduction. For 2), an evolutionary
      iterative process for solving the non-cooperative game theory is exploited to
      handle the non-symmetric weighted adjacency matrix. The abovementioned two stages
      of processes will be conducted for each assumed scale-change factor, experimented
      over a range of possible values, one factor at a time. If there is a match on the
      scale-change factor under experiment, the common visual patterns with the same
      scale-change factor will be extracted. If more than one pattern are extracted,
      the proposed topological splitting method is able to further differentiate among
      them provided that the visual objects are sufficiently far apart from each other.
      Extensive simulation results have clearly demonstrated the superior performance
      accomplished by the proposed digraph approach, compared with those of using the
      undirected graph approach. 

PMID- 24723537
TI  - Fusion of multichannel local and global structural cues for photo aesthetics
      evaluation.
AB  - Photo aesthetic quality evaluation is a fundamental yet under addressed task in
      computer vision and image processing fields. Conventional approaches are
      frustrated by the following two drawbacks. First, both the local and global
      spatial arrangements of image regions play an important role in photo aesthetics.
      However, existing rules, e.g., visual balance, heuristically define which spatial
      distribution among the salient regions of a photo is aesthetically pleasing.
      Second, it is difficult to adjust visual cues from multiple channels
      automatically in photo aesthetics assessment. To solve these problems, we propose
      a new photo aesthetics evaluation framework, focusing on learning the image
      descriptors that characterize local and global structural aesthetics from
      multiple visual channels. In particular, to describe the spatial structure of the
      image local regions, we construct graphlets small-sized connected graphs by
      connecting spatially adjacent atomic regions. Since spatially adjacent graphlets
      distribute closely in their feature space, we project them onto a manifold and
      subsequently propose an embedding algorithm. The embedding algorithm encodes the
      photo global spatial layout into graphlets. Simultaneously, the importance of
      graphlets from multiple visual channels are dynamically adjusted. Finally, these
      post-embedding graphlets are integrated for photo aesthetics evaluation using a
      probabilistic model. Experimental results show that: 1) the visualized graphlets
      explicitly capture the aesthetically arranged atomic regions; 2) the proposed
      approach generalizes and improves four prominent aesthetic rules; and 3) our
      approach significantly outperforms state-of-the-art algorithms in photo
      aesthetics prediction. 

PMID- 24723538
TI  - Multilabel image classification via high-order label correlation driven active
      learning.
AB  - Supervised machine learning techniques have been applied to multilabel image
      classification problems with tremendous success. Despite disparate learning
      mechanisms, their performances heavily rely on the quality of training images.
      However, the acquisition of training images requires significant efforts from
      human annotators. This hinders the applications of supervised learning techniques
      to large scale problems. In this paper, we propose a high-order label correlation
      driven active learning (HoAL) approach that allows the iterative learning
      algorithm itself to select the informative example-label pairs from which it
      learns so as to learn an accurate classifier with less annotation efforts. Four
      crucial issues are considered by the proposed HoAL: 1) unlike binary cases, the
      selection granularity for multilabel active learning need to be fined from
      example to example-label pair; 2) different labels are seldom independent, and
      label correlations provide critical information for efficient learning; 3) in
      addition to pair-wise label correlations, high-order label correlations are also
      informative for multilabel active learning; and 4) since the number of label
      combinations increases exponentially with respect to the number of labels, an
      efficient mining method is required to discover informative label correlations.
      The proposed approach is tested on public data sets, and the empirical results
      demonstrate its effectiveness. 

PMID- 24723539
TI  - Having the Time of Their Life: College Student Stress, Dating and Satisfaction
      with Life.
AB  - A cross-sectional design based on the family ecosystem framework was used to
      examine how students' time spent engaging in social interactions and personal
      behaviours was related to dating, stress and satisfaction with life. The data
      were extracted from the Parental Indulgence of Emerging Adults study and
      consisted of 534 students at a southeastern university. The findings indicated
      that the amount of time involved in non-verbal social interactions, such as
      texting and social networking, along with solitary activities, such as watching
      TV and studying, was negatively related to students' life satisfaction. In
      comparison, being in a relationship and talking to people on the phone were
      positively related to students' life satisfaction. These results have
      implications for family and health professionals along with university wellness
      centres that facilitate student health by incorporating preventative measures to
      help students deal with their stress.

PMID- 24723540
TI  - THE common denominator is microsurgery.

PMID- 24723541
TI  - Retention-property relationships of 1,2,4-triazoles by micellar and reversed
      phase liquid chromatography.
AB  - The properties of 21 1,2,4-triazoles, relevant to their pharmacokinetics, were
      investigated using experimental methods and in silico calculations. The
      lipophilicities of the compounds were determined experimentally using reversed
      phase chromatography and liquid chromatography with micellar mobile phases, or
      they were calculated in silico from their molecular structures. In the reversed
      phase technique, an octadecylsilyl, immobilized artificial membrane and
      immobilized cholesterol were used as the stationary phases. Biological
      descriptors of compounds, i.e. log BB, log KHSA, Caco-2, and fu,brain, were
      determined in silico by using ACD/Percepta software. Principal component analysis
      was used to indicate similarities between chromatographic, partitioning, and
      biological variables. Highly significant relationships were determined to exist
      between the chromatographic parameters and the biological descriptors, especially
      for log BB and log KHSA. The chromatographic parameters measured on the
      cholesterol column were recommended for use in predicting the lipophilic and
      biological properties of the 1,2,4-triazoles that were tested.

PMID- 24723542
TI  - Ultraviolet photodissociation enhances top-down mass spectrometry as demonstrated
      on green fluorescent protein variants.
AB  - Ultraviolet photodissociation (UVPD) is a compelling fragmentation technique with
      great potential to enhance proteomics generally and top-down MS specifically. In
      this issue, Cannon et al. (Proteomics 2014, 14, XXXX-XXXX) use UVPD to perform
      top-down MS on several sequence variants of green fluorescent protein and compare
      the results to CID, higher energy collision induced dissociation, and electron
      transfer dissociation. As compared to the other techniques UVPD produces a wider
      variety of fragment ion types that are relatively evenly distributed across the
      protein sequences. Overall, their results demonstrate enhanced sequence coverage
      and higher confidence in sequence assignment via UVPD MS. Based on these and
      other recent results UVPD is certain to become an increasingly widespread and
      valuable tool for top-down proteomics. 

PMID- 24723544
TI  - FGF23 and vascular calcifications: another piece of the puzzle?

PMID- 24723543
TI  - Management of atherosclerotic renovascular disease after Cardiovascular Outcomes
      in Renal Atherosclerotic Lesions (CORAL).
AB  - Many patients with occlusive atherosclerotic renovascular disease (ARVD) may be
      managed effectively with medical therapy for several years without endovascular
      stenting, as demonstrated by randomized, prospective trials including the
      Cardiovascular Outcomes in Renal Atherosclerotic Lesions (CORAL) trial, the
      Angioplasty and Stenting for Renal Artery Lesions (ASTRAL) trial and the Stent
      Placement and Blood Pressure and Lipid-Lowering for the Prevention of Progression
      of Renal Dysfunction Caused by Atherosclerotic Ostial Stenosis of the Renal
      Artery (STAR) and ASTRAL. These trials share the limitation of excluding subsets
      of patients with high-risk clinical presentations, including episodic pulmonary
      edema and rapidly progressing renal failure and hypertension. Although
      hemodynamically significant, ARVD can reduce renal blood flow and glomerular
      filtration rate; adaptive mechanisms preserve both cortical and medullary
      oxygenation over a wide range of vascular occlusion. Progression of ARVD to
      severe vascular compromise eventually produces cortical hypoxia, however,
      associated with active inflammatory cytokine release and cellular infiltration of
      the renal parenchyma. In such cases ARVD produces a loss of glomerular filtration
      rate that no longer is reversible simply by restoring vessel patency with
      technically successful renal revascularization. Each of these trials reported
      adverse renal functional outcomes ranging between 16 and 22% over periods of 2-5
      years of follow-up. Blood pressure control and medication adjustment may become
      more difficult with declining renal function and may prevent the use of
      angiotensin receptor blocker and angiotensin-converting enzyme inhibitors. The
      objective of this review is to evaluate the current management of ARVD for
      clinical nephrologists in the context of recent randomized clinical trials and
      experimental research. 

PMID- 24723545
TI  - The cost of ignoring acute kidney injury.

PMID- 24723546
TI  - Nephrotic syndrome redux.
AB  - Redux: brought back, resurgent (Wikipedia free dictionary). This essay traces the
      history of the concepts that led to the usage of the term 'nephrotic syndrome'
      beginning ~90 years ago. We then examined the various definitions used for this
      syndrome and modified them to conform to contemporary standards. Remarkably, only
      minor modifications were required. This analysis of a common clinical entity may
      be helpful in ensuring appropriate evaluation of patients suffering from
      nephrotic syndrome and nephrotic-range proteinuria. 

PMID- 24723547
TI  - Does tonsillectomy have a role in the treatment of patients with immunoglobulin A
      nephropathy?

PMID- 24723548
TI  - Job Burnout, Work Engagement and Self-reported Treatment for Health Conditions in
      South Africa.
AB  - The purpose of the study being reported here was to investigate the relationship
      of job burnout and work engagement with self-reported received treatment for
      health conditions (cardiovascular condition, high cholesterol, depression,
      diabetes, hypertension and irritable bowel syndrome), while controlling for age,
      gender, smoking and alcohol use. The sample comprised 7895 employees from a broad
      range of economic sectors in the South African working population. A cross
      sectional survey design was used for the study. Structural equation modelling
      methods were implemented with a weighted least squares approach. The results
      showed that job burnout had a positive relationship with self-reported received
      treatment for depression, diabetes, hypertension and irritable bowel syndrome.
      Work engagement did not have any significant negative or positive relationships
      with the treatment for these health conditions. The results of this study make
      stakeholders aware of the relationship between job burnout, work engagement and
      self-reported treatment for health conditions. Evidence for increased reporting
      of treatment for ill-health conditions due to burnout was found. Therefore,
      attempts should be made to manage job burnout to prevent ill-health outcomes.

PMID- 24723549
TI  - Investigating macromolecular complexes using top-down mass spectrometry.
AB  - MS has emerged as an important tool to investigate noncovalent interactions
      between proteins and various ligands (e.g. other proteins, small molecules, or
      drugs). In particular, ESI under so-called "native conditions" (a.k.a. "native
      MS") has considerably expanded the scope of such investigations. For instance,
      ESI quadrupole time of flight (Q-TOF) instruments have been used to probe the
      precise stoichiometry of protein assemblies, the interactions between subunits
      and the position of subunits within the complex (i.e. defining core and
      peripheral subunits). This review highlights several illustrative native Q-TOF
      based investigations and recent seminal contributions of top-down MS (i.e.
      Fourier transform (FT) MS) to the characterization of noncovalent complexes.
      Combined top-down and native MS, recently demonstrated in "high-mass modified"
      orbitrap mass spectrometers, and further improvements needed for the enhanced
      investigation of biologically significant noncovalent interactions by MS will be
      discussed. 

PMID- 24723550
TI  - Integrating qualitative and quantitative characterization of traditional Chinese
      medicine injection by high-performance liquid chromatography with diode array
      detection and tandem mass spectrometry.
AB  - The present study aims to describe and exemplify an integrated strategy of the
      combination of qualitative and quantitative characterization of a multicomponent
      mixture for the quality control of traditional Chinese medicine injections with
      the example of Danhong injection (DHI). The standardized chemical profile of DHI
      has been established based on liquid chromatography with diode array detection.
      High-performance liquid chromatography coupled with time-of-flight mass
      spectrometry and high-performance liquid chromatography with electrospray
      multistage tandem ion-trap mass spectrometry have been developed to identify the
      major constituents in DHI. The structures of 26 compounds including nucleotides,
      phenolic acids, and flavonoid glycosides were identified or tentatively
      characterized. Meanwhile, the simultaneous determination of seven marker
      constituents, including uridine, adenosine, danshensu, protocatechuic aldehyde, p
      coumaric acid, rosmarinic acid, and salvianolic acid B, in DHI was performed by
      multiwavelength detection based on high-performance liquid chromatography with
      diode array detection. The integrated qualitative and quantitative
      characterization strategy provided an effective and reliable pattern for the
      comprehensive and systematic characterization of the complex traditional Chinese
      medicine system. 

PMID- 24723551
TI  - Epidemiology of multiple congenital anomalies in Europe: a EUROCAT population
      based registry study.
AB  - BACKGROUND: This study describes the prevalence, associated anomalies, and
      demographic characteristics of cases of multiple congenital anomalies (MCA) in 19
      population-based European registries (EUROCAT) covering 959,446 births in 2004
      and 2010. METHODS: EUROCAT implemented a computer algorithm for classification of
      congenital anomaly cases followed by manual review of potential MCA cases by
      geneticists. MCA cases are defined as cases with two or more major anomalies of
      different organ systems, excluding sequences, chromosomal and monogenic
      syndromes. RESULTS: The combination of an epidemiological and clinical approach
      for classification of cases has improved the quality and accuracy of the MCA
      data. Total prevalence of MCA cases was 15.8 per 10,000 births. Fetal deaths and
      termination of pregnancy were significantly more frequent in MCA cases compared
      with isolated cases (p < 0.001) and MCA cases were more frequently prenatally
      diagnosed (p < 0.001). Live born infants with MCA were more often born preterm (p
      < 0.01) and with birth weight < 2500 grams (p < 0.01). Respiratory and ear, face,
      and neck anomalies were the most likely to occur with other anomalies (34% and
      32%) and congenital heart defects and limb anomalies were the least likely to
      occur with other anomalies (13%) (p < 0.01). However, due to their high
      prevalence, congenital heart defects were present in half of all MCA cases. Among
      males with MCA, the frequency of genital anomalies was significantly greater than
      the frequency of genital anomalies among females with MCA (p < 0.001).
      CONCLUSION: Although rare, MCA cases are an important public health issue,
      because of their severity. The EUROCAT database of MCA cases will allow future
      investigation on the epidemiology of these conditions and related clinical and
      diagnostic problems.

PMID- 24723552
TI  - Sensitive determination of polychlorinated biphenyls in environmental water
      samples by headspace solid-phase microextraction with bamboo charcoal@iron oxide
      black fibers prior to gas chromatography with tandem mass spectrometry.
AB  - We have investigated the feasibility of bamboo charcoal@iron oxide black for the
      headspace solid-phase microextraction of polychlorinated biphenyls in
      environmental water samples. Bamboo charcoal@iron oxide black was prepared and
      used as a solid-phase microextraction coating material, and gas chromatography
      with tandem mass spectrometry was used for detection. Several important factors
      affecting the extraction efficiency were systematically investigated and
      optimized. Under the optimum conditions, the experimental data exhibited wide
      linear range over the range 0.2-1000 ng/L and low limits of detection in the
      range of 4.7-22.2 pg/L. The novel coating was successfully used for the
      enrichment and determination of polychlorinated biphenyls in real environmental
      water samples. All these results indicated that bamboo charcoal@iron oxide black
      based headspace solid-phase microextraction coupled to gas chromatography with
      tandem mass spectrometry was an excellent alternative for the sensitive analysis
      of polychlorinated biphenyls at ultratrace levels in the environment. 

PMID- 24723553
TI  - alpha2A-Adrenergic receptor polymorphism potentiates platelet reactivity in
      patients with stable coronary artery disease carrying the cytochrome P450 2C19*2
      genetic variant.
AB  - OBJECTIVE: Platelet alpha2A-adrenergic receptors (ARs) mediate platelet
      aggregation in response to sympathetic stimulation. The 6.3-kb variant of alpha2A
      AR gene is associated with increased epinephrine-induced platelet aggregation in
      healthy volunteers. The cytochrome P450 2C19*2 (CYP2C19*2) loss-of-function
      allele influences P2Y12-mediated platelet inhibition and hence the rate of major
      adverse cardiovascular events. We assessed the influence of 6.3-kb alpha2A-AR
      gene variant on platelet aggregation and its interaction with CYP2C19*2 loss-of
      function allele in patients with stable angina on aspirin and clopidogrel (dual
      antiplatelet therapy). APPROACH AND RESULTS: Aggregation to 5 increasing doses of
      epinephrine (from 0.156 to 10 MUmol/L) was assessed in aggregation units by
      Multiplate Analyzer and platelet reactivity in P2Y12 reactivity units and %
      inhibition by VerifyNow P2Y12 assay before percutaneous revascularization. Gene
      polymorphisms were analyzed with TaqMan Drug Metabolism assay. Of 141 patients,
      aggregation was higher in 6.3-kb carriers (n=52) when compared with wild types
      (n=89) at all epinephrine doses (P<0.05) apart from 10 MUmol/L (P=0.077).
      Percentage inhibition was lower (P=0.048) in 6.3-kb alpha2A-AR carriers.
      Percentage inhibition was lower (P=0.005) and P2Y12 reactivity units was higher
      (P=0.012) in CYP2C19*2 allele carriers. Higher P2Y12 reactivity units (P=0.037)
      and lower percentage inhibition (P=0.009) were observed in carriers of both 6.3
      kb alpha2A-AR variant and CYP2C19*2 allele when compared with wild-type or with
      either mutation on its own. CONCLUSIONS: The 6.3-kb alpha2A-AR variant is
      associated with increased platelet reactivity to epinephrine and has an additive
      effect along with CYP2C19*2 loss-of-function allele on P2Y12-mediated platelet
      responses in patients with stable angina on dual antiplatelet therapy.

PMID- 24723555
TI  - Nepsilon-(carboxymethyl)lysine-receptor for advanced glycation end product axis
      is a key modulator of obesity-induced dysregulation of adipokine expression and
      insulin resistance.
AB  - OBJECTIVE: Dysregulation of inflammatory adipokines by the adipose tissue plays
      an important role in obesity-associated insulin resistance. Pathways leading to
      this dysregulation remain largely unknown. We hypothesized that the receptor for
      advanced glycation end products (RAGE) and the ligand N(epsilon)
      (carboxymethyl)lysine (CML) are increased in adipose tissue and, moreover, that
      activation of the CML-RAGE axis plays an important role in obesity-associated
      inflammation and insulin resistance. APPROACH AND RESULTS: In this study, we
      observed a strong CML accumulation and increased expression of RAGE in adipose
      tissue in obesity. We confirmed in cultured human preadipocytes that adipogenesis
      is associated with increased levels of CML and RAGE. Moreover, CML induced a
      dysregulation of inflammatory adipokines in adipocytes via a RAGE-dependent
      pathway. To test the role of RAGE in obesity-associated inflammation further, we
      constructed an obese mouse model that is deficient for RAGE (ie, RAGE(-/
      )/Leptr(Db-/-) mice). RAGE(-/-)/Leptr(Db-/-) mice displayed an improved
      inflammatory profile and glucose homeostasis when compared with
      RAGE(+/+)/Leptr(Db-/-) mice. In addition, CML was trapped in adipose tissue in
      RAGE(+/+)/Leptr(Db-/-) mice but not in RAGE(-/-)/Leptr(Db-/-). RAGE-mediated
      trapping in adipose tissue provides a mechanism underlying CML accumulation in
      adipose tissue and explaining decreased CML plasma levels in obese subjects.
      Decreased CML plasma levels in obese individuals were strongly associated with
      insulin resistance. CONCLUSIONS: RAGE-mediated CML accumulation in adipose tissue
      and the activation of the CML-RAGE axis are important mechanisms involved in the
      dysregulation of adipokines in obesity, thereby contributing to the development
      of obesity-associated insulin resistance.

PMID- 24723554
TI  - Role of computed tomography for diagnosis and risk stratification of patients
      with suspected or known coronary artery disease.
AB  - Cardiac computed tomographic angiography (CCTA) has emerged as a powerful imaging
      modality for the detection and prognostication of individuals with suspected
      coronary artery disease. Because calcification of coronary plaque occurs in
      proportion to the total atheroma volume, the initial diagnostic potential of CCTA
      focused on the identification and quantification of coronary calcium in low- to
      intermediate-risk individuals, a finding that tracks precisely with the risk of
      incident adverse clinical events. Beyond noncontrast detection of coronary
      calcium, CCTA using iodinated contrast yields incremental information about the
      degree and distribution of coronary plaques and stenosis, as well as vessel wall
      morphology and atherosclerotic plaque features. This additive information offers
      the promise of CCTA to provide a more comprehensive view of total atherosclerotic
      burden because it relates to myocardial ischemia and future adverse clinical
      events. Furthermore, emerging data suggest the prognostic and diagnostic
      importance of stenosis severity detection and atherosclerotic plaque features
      described by CCTA including positive remodeling, low-attenuation plaque, and
      spotty calcification, which have been associated with the vulnerability of
      plaque. We report a summary of the evidence supporting the role of CCTA in the
      detection of subclinical and clinical coronary artery disease in both
      asymptomatic and symptomatic patients and discuss the potential of CCTA to
      augment the identification of at-risk individuals. CCTA and coronary artery
      calcium scoring offer the ability to improve risk stratification, discrimination,
      and reclassification of the risk in patients with suspected coronary artery
      disease and to noninvasively determine the measures of stenosis severity and
      atherosclerotic plaque features.

PMID- 24723556
TI  - Lymphatic vessel insufficiency in hypercholesterolemic mice alters lipoprotein
      levels and promotes atherogenesis.
AB  - OBJECTIVE: Lymphatic vessels collect extravasated fluid and proteins from tissues
      to blood circulation as well as play an essential role in lipid metabolism by
      taking up intestinal chylomicrons. Previous studies have shown that impairment of
      lymphatic vessel function causes lymphedema and fat accumulation, but clear
      connections between arterial pathologies and lymphatic vessels have not been
      described. APPROACH AND RESULTS: Two transgenic mouse strains with lymphatic
      insufficiency (soluble vascular endothelial growth factor 3 [sVEGFR3] and Chy)
      were crossed with atherosclerotic mice deficient of low-density lipoprotein
      receptor and apolipoprotein B48 (LDLR(-/-)/ApoB(100/100)) to study the effects of
      insufficient lymphatic vessel transport on lipoprotein metabolism and
      atherosclerosis. Both sVEGFR3*LDLR(-/-)/ApoB(100/100) mice and Chy*LDLR(-/
      )/ApoB(100/100) mice had higher plasma cholesterol levels compared with LDLR(-/
      )/ApoB(100/100) control mice during both normal chow diet (16.3 and 13.7 versus
      8.2 mmol/L, respectively) and Western-type high-fat diet (eg, after 2 weeks of
      fat diet, 45.9 and 42.6 versus 30.2 mmol/L, respectively). Cholesterol and
      triglyceride levels in very-low-density lipoprotein and low-density lipoprotein
      fractions were increased. Atherosclerotic lesions in young and intermediate
      cohorts of sVEGFR3*LDLR(-/-)/ApoB(100/100) mice progressed faster than in control
      mice (eg, intermediate cohort mice at 6 weeks, 18.3% versus 7.7% of the whole
      aorta, respectively). In addition, lesions in sVEGFR3*LDLR(-/-)/ApoB(100/100)
      mice and Chy*LDLR(-/-)/ApoB(100/100) mice had much less lymphatic vessels than
      lesions in control mice (0.33% and 1.07% versus 7.45% of podoplanin-positive
      vessels, respectively). CONCLUSIONS: We show a novel finding linking impaired
      lymphatic vessels to lipoprotein metabolism, increased plasma cholesterol levels,
      and enhanced atherogenesis.

PMID- 24723557
TI  - Fibrin-targeted magnetic resonance imaging allows in vivo quantification of
      thrombus fibrin content and identifies thrombi amenable for thrombolysis.
AB  - OBJECTIVE: Deep venous thrombosis is a major health problem. Thrombolytic
      therapies are effective in recanalizing the veins and preventing post-thrombotic
      complications, but there is no consensus on selection criteria. The aim of this
      study was to investigate a fibrin-specific MRI contrast agent (EP-2104R) for the
      accurate quantification of thrombus' fibrin content in vivo and for the
      identification of thrombus suitable for thrombolysis. APPROACH AND RESULTS:
      Venous thrombosis was induced in the inferior vena cava of 8- to 10-week-old male
      BALB/C mice and MRI performed 2, 4, 7, 10, 14, and 21 days later. Eighteen mice
      were scanned at each time point pre and 2 hours post injection of EP-2104R (8.0
      MUmol/kg) with 12 mice at each time point used to correlate fibrin contrast
      uptake with thrombus' histological stage and fibrin content. Six mice at each
      time point were immediately subjected to intravascular thrombolytic therapy (10
      mg/kg of tissue-type plasminogen activator). Mice were imaged to assess response
      to lytic therapy 24 hours after thrombolytic treatment. Two mice at each time
      point were scanned post injection of 0.2 mmol/kg of Gd-DTPA (gadolinium with
      diethylenetriaminepentacetate, Magnevist, Schering AG, Berlin, Germany) for
      control purpose. Contrast uptake was correlated positively with the fibrin
      content of the thrombus measured by Western blotting (R(2)=0.889; P<0.001).
      Thrombus relaxation rate (R1) post contrast and the change in visualized thrombus
      size on late gadolinium enhancement inversion recovery MRI pre-EP-2104R and post
      EP-2104R injection were the best predictors for successful thrombolysis (area
      under the curve, 0.989 [95% confidence interval, 0.97-1.00] and 0.994 [95%
      confidence interval, 0.98-1.00] respectively). CONCLUSIONS: MRI with a fibrin
      specific contrast agent accurately estimates thrombus fibrin content in vivo and
      identifies thrombi that are amenable for thrombolysis.

PMID- 24723558
TI  - Matrix metalloproteinase-13 predominates over matrix metalloproteinase-8 as the
      functional interstitial collagenase in mouse atheromata.
AB  - OBJECTIVE: Substantial evidence implicates interstitial collagenases of the
      matrix metalloproteinase (MMP) family in plaque rupture and fatal thrombosis.
      Understanding the compensatory mechanisms that may influence the expression of
      these enzymes and their functions, therefore, has important clinical
      implications. This study assessed in mice the relative effect of the 2 principal
      mouse collagenases on collagen content and other plaque characteristics. APPROACH
      AND RESULTS: Apolipoprotein E-deficient (apoE(-/-)) mice, MMP-13(-/-) apoE(-/-),
      MMP-8(-/-) apoE(-/-) double knockout mice, and MMP-13(-/-) MMP-8(-/-) apoE(-/-)
      triple knockout mice consumed a high-cholesterol diet for 10 and 24 weeks. Both
      double knockout and triple knockout mice showed comparable atherosclerotic lesion
      formation compared with apoE(-/-) controls. Analysis of aortic root sections
      indicated that lesions of MMP-8/MMP-13-deficient and MMP-13-deficient mice
      accumulate more fibrillar collagen than apoE(-/-) controls and MMP-8(-/-) apoE(-/
      ) double knockout. We further tested the relative effect of MMPs on plaque
      collagenolysis using in situ zymography. MMP-13 deletion alone abrogated
      collagenolytic activity in lesions, indicating a predominant role for MMP-13 in
      this process. MMP-13 and MMP-13/MMP-8 deficiency did not alter macrophage content
      but associated with reduced accumulation of smooth muscle cells. CONCLUSIONS:
      These results show that among MMP interstitial collagenases in mice, MMP-13
      prevails over MMP-8 in collagen degradation in atheromata. These findings provide
      a rationale for the identification and selective targeting a predominant
      collagenase for modulating key aspects of plaque structure considered critical in
      clinical complications, although they do not translate directly to human lesions,
      which also contain MMP-1.

PMID- 24723559
TI  - Deficiency of endothelial CXCR4 reduces reendothelialization and enhances
      neointimal hyperplasia after vascular injury in atherosclerosis-prone mice.
AB  - OBJECTIVE: The Cxcl12/Cxcr4 chemokine ligand/receptor axis mediates the
      mobilization of smooth muscle cell progenitors, driving injury-induced neointimal
      hyperplasia. This study aimed to investigate the role of endothelial Cxcr4 in
      neointima formation. APPROACH AND RESULTS: beta-Galactosidase staining using bone
      marrow x kinase (Bmx)-CreER(T2) reporter mice and double immunofluorescence
      revealed an efficient and endothelial-specific deletion of Cxcr4 in Bmx
      CreER(T2+) compared with Bmx-CreER(T2-) Cxcr4-floxed apolipoprotein E-deficient
      (Apoe(-/-)) mice (referred to as Cxcr4(EC-KO)ApoE(-/-) and Cxcr4(EC-WT) ApoE(-/
      ), respectively). Endothelial Cxcr4 deficiency significantly increased wire
      injury-induced neointima formation in carotid arteries from Cxcr4(EC-KO)ApoE(-/-)
      mice. The lesions displayed a higher number of macrophages, whereas the smooth
      muscle cell and collagen content were reduced. This was associated with a
      significant reduction in reendothelialization and endothelial cell proliferation
      in injured Cxcr4(EC-KO)ApoE(-/-) carotids compared with Cxcr4(EC-WT)ApoE(-/-)
      controls. Furthermore, stimulation of human aortic endothelial cells with
      chemokine (C-X-C motif) ligand 12 (CXCL12) significantly enhanced their wound
      healing capacity in an in vitro scratch assay, an effect that could be reversed
      with the CXCR4 antagonist AMD3100. Also, flow cytometric analysis showed a
      reduced mobilization of Sca1(+)Flk1(+)Cd31(+) and of Lin(-)Sca1(+) progenitors in
      Cxcr4(EC-KO) ApoE(-/-) mice after vascular injury, although Cxcr4 surface
      expression was unaltered. No differences could be detected in plasma
      concentrations of Cxcl12, vascular endothelial growth factor, sphingosine 1
      phosphate, or Flt3 (fms-related tyrosine kinase 3) ligand, all cytokines with an
      established role in progenitor cell mobilization. Nonetheless, double
      immunofluorescence revealed a significant reduction in local endothelial Cxcl12
      staining in injured carotids from Cxcr4(EC-KO)ApoE(-/-) mice. CONCLUSIONS:
      Endothelial Cxcr4 is crucial for efficient reendothelialization after vascular
      injury through endothelial wound healing and proliferation, and through the
      mobilization of Sca1(+)Flk1(+)Cd31(+) cells, often referred to as circulating
      endothelial progenitor cells.

PMID- 24723561
TI  - Gold nanoparticle decorated graphene oxide/silica composite stationary phase for
      high-performance liquid chromatography.
AB  - In the initial phase of this study, graphene oxide (GO)/silica was fabricated by
      assembling GO onto the silica particles, and then gold nanoparticles (GNPs) were
      used to modify the GO/silica to prepare a novel stationary phase for high
      performance liquid chromatography. The new stationary phase could be used in both
      reversed-phase chromatography and hydrophilic interaction liquid chromatography
      modes. Good separations of alkylbenzenes, isomerides, amino acids, nucleosides,
      and nucleobases were achieved in both modes. Compared with the GO/silica phase
      and GNPs/silica phase, it is found that except for hydrophilicity, large pi
      electron systems, hydrophobicity, and coordination functions, this new stationary
      phase also exhibited special separation performance due to the combination of 2D
      GO with zero-dimensional GNPs. 

PMID- 24723562
TI  - Application of a magnetic molecularly imprinted polymer for the selective
      extraction and trace detection of lamotrigine in urine and plasma samples.
AB  - Magnetic molecularly imprinted polymers have been synthesized for the selective
      preconcentration and trace determination of lamotrigine (LTG) in urine and plasma
      samples. The magnetic nanoparticles were modified by tetraethyl orthosilicate and
      3-methacryloxypropyl trimethoxysilane before imprinting. The magnetic molecularly
      imprinted polymers were prepared via surface molecular imprinting technique,
      using Fe3 O4 as a magnetic component, LTG as template molecule, methacrylic acid
      as a functional monomer, ethylene glycol dimethacrylate as a cross-linker, and
      2,2'-azobisisobutyronitrile as a radical initiator in methanol/acetonitrile
      (50:50, v/v) as the porogen. The obtained sorbent was characterized using
      scanning electron microscopy, Fourier-transform infrared spectroscopy, X-ray
      diffraction, and thermal analysis. Separation of the sorbent from the sample
      solution was simply achieved by applying an external magnetic field.
      Determination of the extracted drug was performed by high-performance liquid
      chromatography with UV detection. Under the optimum extraction conditions, the
      method detection limits were 0.7 MUg/L (based on S/N of 3) for urine samples and
      0.5 MUg/L for plasma samples. A linear dynamic range of 1-1000 MUg/L was obtained
      for LTF in plasma and urine samples. Finally, the applicability of the proposed
      method was evaluated by extraction and determination of LTG in urine and plasma
      samples. 

PMID- 24723563
TI  - Micro-masters of glioblastoma biology and therapy: increasingly recognized roles
      for microRNAs.
AB  - MicroRNAs are small noncoding RNAs encoded in eukaryotic genomes that have been
      found to play critical roles in most biological processes, including cancer. This
      is true for glioblastoma, the most common and lethal primary brain tumor, for
      which microRNAs have been shown to strongly influence cell viability, stem cell
      characteristics, invasiveness, angiogenesis, metabolism, and immune evasion.
      Developing microRNAs as prognostic markers or as therapeutic agents is showing
      increasing promise and has potential to reach the clinic in the next several
      years. This succinct review summarizes current progress and future directions in
      this exciting and steadily expanding field. 

PMID- 24723564
TI  - Significance of interleukin-13 receptor alpha 2-targeted glioblastoma therapy.
AB  - Glioblastoma multiforme (GBM) remains one of the most lethal primary brain tumors
      despite surgical and therapeutic advancements. Targeted therapies of neoplastic
      diseases, including GBM, have received a great deal of interest in recent years.
      A highly studied target of GBM is interleukin-13 receptor alpha chain variant 2
      (IL13Ralpha2). Targeted therapies against IL13Ralpha2 in GBM include fusion
      chimera proteins of IL-13 and bacterial toxins, nanoparticles, and oncolytic
      viruses. In addition, immunotherapies have been developed using monoclonal
      antibodies and cell-based strategies such as IL13Ralpha2-pulsed dendritic cells
      and IL13Ralpha2-targeted chimeric antigen receptor-modified T cells. Advanced
      therapeutic development has led to the completion of phase I clinical trials for
      chimeric antigen receptor-modified T cells and phase III clinical trials for IL
      13-conjugated bacterial toxin, with promising outcomes. Selective expression of
      IL13Ralpha2 on tumor cells, while absent in the surrounding normal brain tissue,
      has motivated continued study of IL13Ralpha2 as an important candidate for
      targeted glioma therapy. Here, we review the preclinical and clinical studies
      targeting IL13Ralpha2 in GBM and discuss new advances and promising applications.

PMID- 24723565
TI  - Incidence and relative survival of anaplastic astrocytomas.
AB  - BACKGROUND: The purpose of this study was to investigate the relationship between
      age and the incidence and relative survival of anaplastic astrocytoma (AA).
      METHODS: Data from the Surveillance, Epidemiology and End Results database were
      used to identify 3202 patients with AA. These data were analyzed to assess
      incidence rates, relative survival, and the standardized mortality ratio across
      age groups. Time trends were modeled using delayed-entry modeling. RESULTS: The
      overall incidence of AA was an age-adjusted rate of 3.5 per million person/years.
      The overall age-standardized 5- and 10-year relative survival rates of
      populations with AA were 23.6% and 15.1%, respectively. The overall standardized
      mortality ratio for the entire cohort was 46 (95% confidence interval: 45, 48).
      CONCLUSIONS: Patients with a diagnosis of AA are 46 times more likely to die than
      persons matched for age/sex/year of the general population. The effect of age on
      survival is present for only the first 2 years postdiagnosis. Measuring the
      effect of age on survival for populations with an AA is not amenable to using
      models with proportional hazards as an assumption because of the presence of a
      reverse fork-type interaction.

PMID- 24723568
TI  - Purification of supercoiled plasmid DNA from clarified bacterial lysate by
      arginine-affinity chromatography: effects of spacer arms and ligand density.
AB  - Efficient loading on a chromatographic column is the dilemma of the process
      development faced by engineers in plasmid DNA purification. In this research,
      novel arginine-affinity chromatographic beads were prepared to investigate the
      effect of spacer arm and ligand density to their chromatographic performance for
      the purification of plasmid. The result indicated that dynamic binding capacity
      for plasmid increased with an increasing ligand density and carbon number of
      spacer arm, and the highest binding capacity for plasmid of 6.32 mg/mL bead was
      observed in the column of arginine bead with a ligand density of 47 mmol/L and 10
      atom carbon spacer. Furthermore, this arginine bead exhibited better selectivity
      to supercoiled (sc) plasmid. The evidence of a linear gradient elution suggested
      further that the binding of plasmid on arginine beads was driven by electrostatic
      interaction and hydrogen bonding. Hence, sc plasmid could successfully be
      purified from clarified lysate by two-stepwise elution of salt concentration. By
      the refinement of the elution scheme and loading volume of clarified lysate, the
      column of arginine bead with a ligand density of 47 mmol/L exhibited the highest
      recovery yield and a much higher productivity among arginine-affinity columns.
      Therefore, reshaped arginine beads provided more feasible and practical
      application in the preparation of sc plasmid from clarified lysate. 

PMID- 24723566
TI  - Mitotic index, microvascular proliferation, and necrosis define 3 groups of
      1p/19q codeleted anaplastic oligodendrogliomas associated with different genomic
      alterations.
AB  - BACKGROUND: The aim of this study was to correlate histological features and
      molecular characteristics in anaplastic oligodendrogliomas (AOs). METHODS: The
      histological characteristics of 203 AO patients, enrolled in the French national
      network POLA, were analyzed. The genomic profiles of 191 cases were studied using
      genomic arrays. IDH mutational status was assessed by immunohistochemistry and
      direct sequencing. RESULTS: 1p/19q codeletion was present in 79% of cases and was
      associated with alpha-internexin expression (P < 10(-4)), IDH1/2 mutation (P <
      10(-4)), chromosome 4 loss (P < 10(-3)), and better overall survival (P < 10(
      4)). Based on mitotic index, microvascular proliferation (MVP), and necrosis, 3
      groups of 1p/19q codeleted AOs were identified: (group 1) AO with more than 5
      mitoses per 10-HPF, no MVP, and no necrosis; (group 2) AO with MVP and no
      necrosis; and (group 3) AO with MVP and necrosis. Compared with group 1, groups 2
      and 3 AOs had a higher mean Ki-67 proliferation index and a higher rate of 9p and
      9q losses. Compared with group 2, group 3 AOs had a higher number of chromosomal
      alterations including chromosome 4 loss. In the subgroup of 157 1p/19q codeleted
      AOs, chromosomal instability was associated with shorter progression-free
      survival (P = .024) and shorter overall survival (P = .023). CONCLUSIONS: The
      present study shows that oligodendrogliomas with classic histological features
      remain a molecularly heterogeneous entity and should be stratified according to
      1p/19q status because of its major prognostic relevance. Moreover, 1p/19q
      codeleted AOs are also heterogeneous. Interestingly, mitotic index, MVP, and
      necrosis help to classify them into 3 groups associated with distinct genomic
      alterations.

PMID- 24723569
TI  - Letter to the Editor: On the term 'interaction' and related phrases in the
      literature on Random Forests.
AB  - In an interesting and quite exhaustive review on Random Forests (RF) methodology
      in bioinformatics Touw et al. address--among other topics--the problem of the
      detection of interactions between variables based on RF methodology. We feel that
      some important statistical concepts, such as 'interaction', 'conditional
      dependence' or 'correlation', are sometimes employed inconsistently in the
      bioinformatics literature in general and in the literature on RF in particular.
      In this letter to the Editor, we aim to clarify some of the central statistical
      concepts and point out some confusing interpretations concerning RF given by Touw
      et al. and other authors.

PMID- 24723570
TI  - Toward more realistic drug-target interaction predictions.
AB  - A number of supervised machine learning models have recently been introduced for
      the prediction of drug-target interactions based on chemical structure and
      genomic sequence information. Although these models could offer improved means
      for many network pharmacology applications, such as repositioning of drugs for
      new therapeutic uses, the prediction models are often being constructed and
      evaluated under overly simplified settings that do not reflect the real-life
      problem in practical applications. Using quantitative drug-target bioactivity
      assays for kinase inhibitors, as well as a popular benchmarking data set of
      binary drug-target interactions for enzyme, ion channel, nuclear receptor and G
      protein-coupled receptor targets, we illustrate here the effects of four factors
      that may lead to dramatic differences in the prediction results: (i) problem
      formulation (standard binary classification or more realistic regression
      formulation), (ii) evaluation data set (drug and target families in the
      application use case), (iii) evaluation procedure (simple or nested cross
      validation) and (iv) experimental setting (whether training and test sets share
      common drugs and targets, only drugs or targets or neither). Each of these
      factors should be taken into consideration to avoid reporting overoptimistic drug
      target interaction prediction results. We also suggest guidelines on how to make
      the supervised drug-target interaction prediction studies more realistic in terms
      of such model formulations and evaluation setups that better address the inherent
      complexity of the prediction task in the practical applications, as well as novel
      benchmarking data sets that capture the continuous nature of the drug-target
      interactions for kinase inhibitors. 

PMID- 24723572
TI  - Saliency-based selection of gradient vector flow paths for content aware image
      resizing.
AB  - Content-aware image resizing techniques allow to take into account the visual
      content of images during the resizing process. The basic idea beyond these
      algorithms is the removal of vertical and/or horizontal paths of pixels (i.e.,
      seams) containing low salient information. In this paper, we present a method
      which exploits the gradient vector flow (GVF) of the image to establish the paths
      to be considered during the resizing. The relevance of each GVF path is
      straightforward derived from an energy map related to the magnitude of the GVF
      associated to the image to be resized. To make more relevant, the visual content
      of the images during the content-aware resizing, we also propose to select the
      generated GVF paths based on their visual saliency properties. In this way,
      visually important image regions are better preserved in the final resized image.
      The proposed technique has been tested, both qualitatively and quantitatively, by
      considering a representative data set of 1000 images labeled with corresponding
      salient objects (i.e., ground-truth maps). Experimental results demonstrate that
      our method preserves crucial salient regions better than other state-of-the-art
      algorithms.

PMID- 24723571
TI  - Novel biomimetic tripolymer scaffolds consisting of chitosan, collagen type 1,
      and hyaluronic acid for bone marrow-derived human mesenchymal stem cells-based
      bone tissue engineering.
AB  - Human bone marrow-derived mesenchymal stem cells (hMSCs) are an ideal osteogenic
      cell source for bone tissue engineering (BTE). A scaffold, in the context of BTE,
      is the extracellular matrix (ECM) that provides the unique microenvironment and
      play significant role in regulating cell behavior, differentiation, and
      development in an in vitro culture system. In this study, we have developed novel
      biomimetic tripolymer scaffolds for BTE using an ECM protein, collagen type 1; an
      ECM glycosaminoglycan, hyaluronic acid; and a natural osteoconductive polymer,
      chitosan. The scaffolds were characterized by scanning electron microscopy (SEM)
      and swelling ratio. The scaffolds were seeded with hMSCs and tested for
      cytocompatibility and osteogenic potential. The scaffolds supported cell
      adhesion, enhanced cell proliferation, promoted cell migration, showed good cell
      viability, and osteogenic potential. The cells were able to migrate out from the
      scaffolds in favorable conditions. SEM, alkaline phosphatase assay, and
      immunofluorescent staining confirmed the differentiation of hMSCs to osteogenic
      lineage in the scaffolds. In conclusion, we have successfully developed
      biomimetic scaffolds that supported the proliferation and differentiation of
      hMSCs. These scaffolds hold great promise as a cell-delivery vehicle for
      regenerative therapies and as a support system for enhancing bone regeneration.

PMID- 24723573
TI  - Online glocal transfer for automatic figure-ground segmentation.
AB  - This paper addresses the problem of automatic figure-ground segmentation, which
      aims at automatically segmenting out all foreground objects from background. The
      underlying idea of this approach is to transfer segmentation masks of globally
      and locally (glocally) similar exemplars into the query image. For this purpose,
      we propose a novel high-level image representation method named as object
      oriented descriptor. Using this descriptor, a set of exemplar images glocally
      similar to the query image is retrieved. Then, using over-segmented regions of
      these retrieved exemplars, a discriminative classifier is learned on-the-fly and
      subsequently used to predict foreground probability for the query image. Finally,
      the optimal segmentation is obtained by combining the online prediction with
      typical energy optimization of Markov random field. The proposed approach has
      been extensively evaluated on three datasets, including Pascal VOC 2010, VOC 2011
      segmentation challenges, and iCoseg dataset. Experiments show that the proposed
      approach outperforms state-of-the-art methods and has the potential to segment
      large-scale images containing unknown objects, which never appear in the exemplar
      images.

PMID- 24723574
TI  - Learning joint intensity-depth sparse representations.
AB  - This paper presents a method for learning overcomplete dictionaries of atoms
      composed of two modalities that describe a 3D scene: 1) image intensity and 2)
      scene depth. We propose a novel joint basis pursuit (JBP) algorithm that finds
      related sparse features in two modalities using conic programming and we
      integrate it into a two-step dictionary learning algorithm. The JBP differs from
      related convex algorithms because it finds joint sparsity models with different
      atoms and different coefficient values for intensity and depth. This is crucial
      for recovering generative models where the same sparse underlying causes (3D
      features) give rise to different signals (intensity and depth). We give a bound
      for recovery error of sparse coefficients obtained by JBP, and show numerically
      that JBP is superior to the group lasso algorithm. When applied to the Middlebury
      depth-intensity database, our learning algorithm converges to a set of related
      features, such as pairs of depth and intensity edges or image textures and depth
      slants. Finally, we show that JBP outperforms state of the art methods on depth
      inpainting for time-of-flight and Microsoft Kinect 3D data.

PMID- 24723575
TI  - A regularized approach for geodesic-based semisupervised multimanifold learning.
AB  - Geodesic distance, as an essential measurement for data dissimilarity, has been
      successfully used in manifold learning. However, most geodesic distance-based
      manifold learning algorithms have two limitations when applied to classification:
      1) class information is rarely used in computing the geodesic distances between
      data points on manifolds and 2) little attention has been paid to building an
      explicit dimension reduction mapping for extracting the discriminative
      information hidden in the geodesic distances. In this paper, we regard geodesic
      distance as a kind of kernel, which maps data from linearly inseparable space to
      linear separable distance space. In doing this, a new semisupervised manifold
      learning algorithm, namely regularized geodesic feature learning algorithm, is
      proposed. The method consists of three techniques: a semisupervised graph
      construction method, replacement of original data points with feature vectors
      which are built by geodesic distances, and a new semisupervised dimension
      reduction method for feature vectors. Experiments on the MNIST, USPS handwritten
      digit data sets, MIT CBCL face versus nonface data set, and an intelligent
      traffic data set show the effectiveness of the proposed algorithm.

PMID- 24723567
TI  - Germline rearrangements in families with strong family history of glioma and
      malignant melanoma, colon, and breast cancer.
AB  - BACKGROUND: Although familial susceptibility to glioma is known, the genetic
      basis for this susceptibility remains unidentified in the majority of glioma
      specific families. An alternative approach to identifying such genes is to
      examine cancer pedigrees, which include glioma as one of several cancer
      phenotypes, to determine whether common chromosomal modifications might account
      for the familial aggregation of glioma and other cancers. METHODS: Germline
      rearrangements in 146 glioma families (from the Gliogene Consortium;
      http://www.gliogene.org/) were examined using multiplex ligation-dependent probe
      amplification. These families all had at least 2 verified glioma cases and a
      third reported or verified glioma case in the same family or 2 glioma cases in
      the family with at least one family member affected with melanoma, colon, or
      breast cancer.The genomic areas covering TP53, CDKN2A, MLH1, and MSH2 were
      selected because these genes have been previously reported to be associated with
      cancer pedigrees known to include glioma. RESULTS: We detected a single
      structural rearrangement, a deletion of exons 1-6 in MSH2, in the proband of one
      family with 3 cases with glioma and one relative with colon cancer. CONCLUSIONS:
      Large deletions and duplications are rare events in familial glioma cases, even
      in families with a strong family history of cancers that may be involved in known
      cancer syndromes.

PMID- 24723576
TI  - Residual component analysis of hyperspectral images--application to joint
      nonlinear unmixing and nonlinearity detection.
AB  - This paper presents a nonlinear mixing model for joint hyperspectral image
      unmixing and nonlinearity detection. The proposed model assumes that the pixel
      reflectances are linear combinations of known pure spectral components corrupted
      by an additional nonlinear term, affecting the end members and contaminated by an
      additive Gaussian noise. A Markov random field is considered for nonlinearity
      detection based on the spatial structure of the nonlinear terms. The observed
      image is segmented into regions where nonlinear terms, if present, share similar
      statistical properties. A Bayesian algorithm is proposed to estimate the
      parameters involved in the model yielding a joint nonlinear unmixing and
      nonlinearity detection algorithm. The performance of the proposed strategy is
      first evaluated on synthetic data. Simulations conducted with real data show the
      accuracy of the proposed unmixing and nonlinearity detection strategy for the
      analysis of hyperspectral images.

PMID- 24723577
TI  - Modeling the time--varying subjective quality of HTTP video streams with rate
      adaptations.
AB  - Newly developed hypertext transfer protocol (HTTP)-based video streaming
      technologies enable flexible rate-adaptation under varying channel conditions.
      Accurately predicting the users' quality of experience (QoE) for rate-adaptive
      HTTP video streams is thus critical to achieve efficiency. An important aspect of
      understanding and modeling QoE is predicting the up-to-the-moment subjective
      quality of a video as it is played, which is difficult due to hysteresis effects
      and nonlinearities in human behavioral responses. This paper presents a
      Hammerstein-Wiener model for predicting the time-varying subjective quality
      (TVSQ) of rate-adaptive videos. To collect data for model parameterization and
      validation, a database of longer duration videos with time-varying distortions
      was built and the TVSQs of the videos were measured in a large-scale subjective
      study. The proposed method is able to reliably predict the TVSQ of rate adaptive
      videos. Since the Hammerstein-Wiener model has a very simple structure, the
      proposed method is suitable for online TVSQ prediction in HTTP-based streaming.

PMID- 24723578
TI  - Actively learning human gaze shifting paths for semantics-aware photo cropping.
AB  - Photo cropping is a widely used tool in printing industry, photography, and
      cinematography. Conventional cropping models suffer from the following three
      challenges. First, the deemphasized role of semantic contents that are many times
      more important than low-level features in photo aesthetics. Second, the absence
      of a sequential ordering in the existing models. In contrast, humans look at
      semantically important regions sequentially when viewing a photo. Third, the
      difficulty of leveraging inputs from multiple users. Experience from multiple
      users is particularly critical in cropping as photo assessment is quite a
      subjective task. To address these challenges, this paper proposes semantics-aware
      photo cropping, which crops a photo by simulating the process of humans
      sequentially perceiving semantically important regions of a photo. We first
      project the local features (graphlets in this paper) onto the semantic space,
      which is constructed based on the category information of the training photos. An
      efficient learning algorithm is then derived to sequentially select semantically
      representative graphlets of a photo, and the selecting process can be interpreted
      by a path, which simulates humans actively perceiving semantics in a photo.
      Furthermore, we learn a prior distribution of such active graphlet paths from
      training photos that are marked as aesthetically pleasing by multiple users. The
      learned priors enforce the corresponding active graphlet path of a test photo to
      be maximally similar to those from the training photos. Experimental results show
      that: 1) the active graphlet path accurately predicts human gaze shifting, and
      thus is more indicative for photo aesthetics than conventional saliency maps and
      2) the cropped photos produced by our approach outperform its competitors in both
      qualitative and quantitative comparisons.

PMID- 24723579
TI  - PHOTO QUIZ. Recurrent buttock cellulitis in a female adolescent.

PMID- 24723587
TI  - Conservation biology. Can cloning revive Spain's extinct mountain goat?

PMID- 24723582
TI  - Four-group classification of left ventricular hypertrophy based on ventricular
      concentricity and dilatation identifies a low-risk subset of eccentric
      hypertrophy in hypertensive patients.
AB  - BACKGROUND: Left ventricular hypertrophy (LVH; high LV mass [LVM]) is
      traditionally classified as concentric or eccentric based on LV relative wall
      thickness. We evaluated the prediction of subsequent adverse events in a new 4
      group LVH classification based on LV dilatation (high LV end-diastolic volume
      [EDV] index) and concentricity (mass/end-diastolic volume [M/EDV](2/3)) in
      hypertensive patients. METHODS AND RESULTS: In the Losartan Intervention for
      Endpoint Reduction (LIFE) echocardiography substudy, 939 hypertensive patients
      with measurable LVM at baseline were randomized to a mean of 4.8 years of
      losartan- or atenolol-based treatment. Patients with LVH (LVM/body surface area
      >=116 and >=96 g/m(2) in men and woman, respectively) were divided into 4 groups
      concentric nondilated (increased M/EDV, normal EDV), eccentric dilated (increased
      EDV, normal M/EDV), concentric dilated (increased M/EDV and EDV), and eccentric
      nondilated (normal M/EDV and EDV)-and compared with patients with normal LVM.
      Time-varying LVH classes were tested for association with all-cause and
      cardiovascular mortality and a composite end point of myocardial infarction,
      stroke, heart failure, and cardiovascular death in multivariable Cox analyses. At
      baseline, the LVs were categorized as eccentric nondilated in 12%, eccentric
      dilated in 20%, concentric nondilated in 29%, concentric dilated in 14%, and
      normal LVM in 25%. Treatment changed the prevalence of 4 LVH groups to 23%, 4%,
      5%, and 7%; 62% had normal LVM after 4 years. In time-varying Cox analyses,
      compared with normal LVM, those with eccentric dilated and both concentric
      nondilated and dilated LVH had increased risks of all-cause or cardiovascular
      mortality or the composite end point, whereas the eccentric nondilated group did
      not. CONCLUSIONS: Hypertensive patients with relatively mild LVH without either
      increased LV volume or concentricity have similar risk of all-cause mortality or
      cardiovascular events because hypertensive patients with normal LVM seem to be a
      low-risk group. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov.
      Unique identifier: NCT00338260.

PMID- 24723588
TI  - Planetary science. NASA to researchers: sell your mission or be terminated.

PMID- 24723589
TI  - Infectious disease. Are bats spreading Ebola across sub-Saharan Africa?

PMID- 24723590
TI  - Seismology. Human activity may have triggered fatal Italian earthquakes, panel
      says.

PMID- 24723591
TI  - Neglected tropical diseases. Oral antibiotic raises hopes of eradicating yaws.

PMID- 24723592
TI  - Mesoamerica's mystery killer.

PMID- 24723593
TI  - A Balkan riddle's serendipitous solution.

PMID- 24723596
TI  - A new threat to European vultures.

PMID- 24723594
TI  - Immunotherapy: it takes a village.

PMID- 24723597
TI  - India puts informed consent on camera.

PMID- 24723599
TI  - Education technology. Computer-guided inquiry to improve science learning.

PMID- 24723600
TI  - Neuroscience. An olfactory critical period.

PMID- 24723601
TI  - Botany. Patterning cues from the altruistic sibling.

PMID- 24723602
TI  - Astronomy. Pulsar beams--big and bright.

PMID- 24723603
TI  - Physics. The advantages of extra entanglement.

PMID- 24723604
TI  - Materials science. Materials both tough and soft.

PMID- 24723605
TI  - Central cell-derived peptides regulate early embryo patterning in flowering
      plants.
AB  - Plant embryogenesis initiates with the establishment of an apical-basal axis;
      however, the molecular mechanisms accompanying this early event remain unclear.
      Here, we show that a small cysteine-rich peptide family is required for formation
      of the zygotic basal cell lineage and proembryo patterning in Arabidopsis. EMBRYO
      SURROUNDING FACTOR 1 (ESF1) peptides accumulate before fertilization in central
      cell gametes and thereafter in embryo-surrounding endosperm cells. Biochemical
      and structural analyses revealed cleavage of ESF1 propeptides to form
      biologically active mature peptides. Further, these peptides act in a non-cell
      autonomous manner and synergistically with the receptor-like kinase SHORT
      SUSPENSOR to promote suspensor elongation through the YODA mitogen-activated
      protein kinase pathway. Our findings demonstrate that the second female gamete
      and its sexually derived endosperm regulate early embryonic patterning in
      flowering plants. 

PMID- 24723606
TI  - Flies evade looming targets by executing rapid visually directed banked turns.
AB  - Avoiding predators is an essential behavior in which animals must quickly
      transform sensory cues into evasive actions. Sensory reflexes are particularly
      fast in flying insects such as flies, but the means by which they evade aerial
      predators is not known. Using high-speed videography and automated tracking of
      flies in combination with aerodynamic measurements on flapping robots, we show
      that flying flies react to looming stimuli with directed banked turns. The
      maneuver consists of a rapid body rotation followed immediately by an active
      counter-rotation and is enacted by remarkably subtle changes in wing motion.
      These evasive maneuvers of flies are substantially faster than steering maneuvers
      measured previously and indicate the existence of sensory-motor circuitry that
      can reorient the fly's flight path within a few wingbeats. 

PMID- 24723607
TI  - Ultrafast switching to a stable hidden quantum state in an electronic crystal.
AB  - Hidden states of matter may be created if a system out of equilibrium follows a
      trajectory to a state that is inaccessible or does not exist under normal
      equilibrium conditions. We found such a hidden (H) electronic state in a layered
      dichalcogenide crystal of 1T-TaS2 (the trigonal phase of tantalum disulfide)
      reached as a result of a quench caused by a single 35-femtosecond laser pulse. In
      comparison to other states of the system, the H state exhibits a large drop of
      electrical resistance, strongly modified single-particle and collective-mode
      spectra, and a marked change of optical reflectivity. The H state is stable until
      a laser pulse, electrical current, or thermal erase procedure is applied, causing
      it to revert to the thermodynamic ground state. 

PMID- 24723608
TI  - Unfolding the laws of star formation: the density distribution of molecular
      clouds.
AB  - The formation of stars shapes the structure and evolution of entire galaxies. The
      rate and efficiency of this process are affected substantially by the density
      structure of the individual molecular clouds in which stars form. The most
      fundamental measure of this structure is the probability density function of
      volume densities (rho-PDF), which determines the star formation rates predicted
      with analytical models. This function has remained unconstrained by observations.
      We have developed an approach to quantify rho-PDFs and establish their relation
      to star formation. The rho-PDFs instigate a density threshold of star formation
      and allow us to quantify the star formation efficiency above it. The rho-PDFs
      provide new constraints for star formation theories and correctly predict several
      key properties of the star-forming interstellar medium. 

PMID- 24723609
TI  - Toughening elastomers with sacrificial bonds and watching them break.
AB  - Elastomers are widely used because of their large-strain reversible
      deformability. Most unfilled elastomers suffer from a poor mechanical strength,
      which limits their use. Using sacrificial bonds, we show how brittle, unfilled
      elastomers can be strongly reinforced in stiffness and toughness (up to 4
      megapascals and 9 kilojoules per square meter) by introducing a variable
      proportion of isotropically prestretched chains that can break and dissipate
      energy before the material fails. Chemoluminescent cross-linking molecules, which
      emit light as they break, map in real time where and when many of these internal
      bonds break ahead of a propagating crack. The simple methodology that we use to
      introduce sacrificial bonds, combined with the mapping of where bonds break, has
      the potential to stimulate the development of new classes of unfilled tough
      elastomers and better molecular models of the fracture of soft materials. 

PMID- 24723610
TI  - A developmental switch of axon targeting in the continuously regenerating mouse
      olfactory system.
AB  - The mammalian olfactory system has the natural capacity to regenerate throughout
      the animal's life span. Despite constant neurogenesis, olfactory sensory neurons
      project to precise, stereotypical positions in the brain. Here, we identify a
      critical period of olfactory sensory axon targeting during postnatal development
      in mouse. Perturbing axon projection beyond postnatal day 7 permanently disrupts
      targeting specificity of the sensory neurons. In addition, we find that the
      establishment of the convergence map requires perinatal sensory neurons. Late
      born neurons appear to connect with prospective glomeruli based on homotypic
      interactions among neurons expressing the same odorant receptor. Our results
      reveal a developmental switch in axon guidance and a mechanism of circuit
      integration of adult-born neurons. 

PMID- 24723611
TI  - A critical period defined by axon-targeting mechanisms in the murine olfactory
      bulb.
AB  - The olfactory system remains plastic throughout life because of continuous
      neurogenesis of sensory neurons in the nose and inhibitory interneurons in the
      olfactory bulb. Here, we reveal that transgenic expression of an odorant receptor
      has non-cell autonomous effects on axons expressing this receptor from the
      endogenous gene. Perinatal expression of transgenic odorant receptor causes
      rerouting of like axons to new glomeruli, whereas expression after the sensory
      map is established does not lead to rerouting. Further, chemical ablation of the
      map after rerouting does not restore the normal map, even when the transgenic
      receptor is no longer expressed. Our results reveal that glomeruli are designated
      as targets for sensory neurons expressing specific odorant receptors during a
      critical period in the formation of the olfactory sensory map. 

PMID- 24723612
TI  - Acquisition of germ plasm accelerates vertebrate evolution.
AB  - Primordial germ cell (PGC) specification occurs either by induction from
      pluripotent cells (epigenesis) or by a cell-autonomous mechanism mediated by germ
      plasm (preformation). Among vertebrates, epigenesis is basal, whereas germ plasm
      has evolved convergently across lineages and is associated with greater
      speciation. We compared protein-coding sequences of vertebrate species that
      employ preformation with their sister taxa that use epigenesis and demonstrate
      that genes evolve more rapidly in species containing germ plasm. Furthermore,
      differences in rates of evolution appear to cause phylogenetic incongruence in
      protein-coding sequence comparisons between vertebrate taxa. Our results support
      the hypothesis that germ plasm liberates constraints on somatic development and
      that enhanced evolvability drives the evolution of germ plasm. 

PMID- 24723613
TI  - Mapping the cellular response to small molecules using chemogenomic fitness
      signatures.
AB  - Genome-wide characterization of the in vivo cellular response to perturbation is
      fundamental to understanding how cells survive stress. Identifying the proteins
      and pathways perturbed by small molecules affects biology and medicine by
      revealing the mechanisms of drug action. We used a yeast chemogenomics platform
      that quantifies the requirement for each gene for resistance to a compound in
      vivo to profile 3250 small molecules in a systematic and unbiased manner. We
      identified 317 compounds that specifically perturb the function of 121 genes and
      characterized the mechanism of specific compounds. Global analysis revealed that
      the cellular response to small molecules is limited and described by a network of
      45 major chemogenomic signatures. Our results provide a resource for the
      discovery of functional interactions among genes, chemicals, and biological
      processes. 

PMID- 24723615
TI  - Relation between changes in foveal choroidal thickness and 1-year results of
      ranibizumab therapy for polypoidal choroidal vasculopathy.
AB  - AIM: To determine a correlation between changes in the subfoveal choroidal
      thickness and outcomes 1 year after ranibizumab therapy for polypoidal choroidal
      vasculopathy (PCV). METHODS: We prospectively studied 89 consecutive eyes with
      treatment-naive symptomatic PCV and 1 year of follow-up after treatment. The
      choroidal thickness was measured monthly by optical coherence tomography using
      enhanced-depth imaging and the correlation between the changes in the choroidal
      thickness and outcomes 1 year after treatment was analysed. RESULTS: 86 eyes
      followed for 1 year were ultimately analysed. The mean logarithm of the minimum
      angle of resolution visual acuity (0.33+/-0.35) 1 year after the first injection
      significantly (p=0.001) improved compared to baseline (0.42+/-0.37). The mean
      choroidal and foveal retinal thicknesses decreased significantly (p=0.001 for
      both comparisons) from 271 and 347 MUm to 212 and 203 MUm, respectively. The
      amplitude of the change in the subfoveal choroidal thickness during the 1-year
      follow-up in eyes in which the polypoidal lesions resolved 1 year after the first
      injection (89+/-94 MUm) was significantly (p=0.022) greater than in eyes in which
      the polypoidal lesions remained (45+/-109 MUm). CONCLUSIONS: The subfoveal
      choroidal thickness decreased during ranibizumab therapy, which was associated
      with resolved polypoidal lesions and foveal retinal thickness, and may be
      associated with PCV activity.

PMID- 24723614
TI  - Interneurons from embryonic development to cell-based therapy.
AB  - Many neurologic and psychiatric disorders are marked by imbalances between neural
      excitation and inhibition. In the cerebral cortex, inhibition is mediated largely
      by GABAergic (gamma-aminobutyric acid-secreting) interneurons, a cell type that
      originates in the embryonic ventral telencephalon and populates the cortex
      through long-distance tangential migration. Remarkably, when transplanted from
      embryos or in vitro culture preparations, immature interneurons disperse and
      integrate into host brain circuits, both in the cerebral cortex and in other
      regions of the central nervous system. These features make interneuron
      transplantation a powerful tool for the study of neurodevelopmental processes
      such as cell specification, cell death, and cortical plasticity. Moreover,
      interneuron transplantation provides a novel strategy for modifying neural
      circuits in rodent models of epilepsy, Parkinson's disease, mood disorders, and
      chronic pain. 

PMID- 24723616
TI  - 12-month results of the standardised combination therapy for diabetic macular
      oedema: intravitreal bevacizumab and navigated retinal photocoagulation.
AB  - AIM: To evaluate the efficacy of a standardised combination therapy for
      clinically significant diabetic macular oedema using bevacizumab injections
      followed by navigated laser photocoagulation to stabilise retinal thickness.
      METHODS: In this pilot study we retrospectively reviewed charts and imaging of 23
      eyes treated with the standardised combination regimen. Eyes initially received
      monthly bevacizumab injections, followed by navigated laser photocoagulation when
      central retinal thickness (CRT) was <440 um. Patients were then followed monthly
      for 12 months. RESULTS: At the time of navigated laser after bevacizumab
      treatment mean vision gain was +10.4 Early Treatment Diabetic Retinopathy Study
      letters (p<0.01) and CRT reduction was 146 um (p<0.001). At 12 months from
      baseline, the vision gain remained stable at +10.6 Early Treatment Diabetic
      Retinopathy Study letters (p<0.01), and CRT reduction was stable at 137 um
      (p<0.001). At 12 months from laser, the vision gain was 7.8 letters from baseline
      (p<0.01), with no significant change compared with the gain at 12 months from
      baseline (p=0.108). At 12 months from laser, CRT reduction was 125 um from
      baseline (p<0.001), with no significant change compared with CRT reduction at 12
      months from baseline (p=0.601). Total injections needed were 4.4 from baseline to
      month 12, with 1.3 reinjection needed after laser. 57% of the eyes didn't require
      injections after laser, while 43% needed two additional injections. CONCLUSIONS:
      Standardised combination therapy using bevacizumab injections followed by
      navigated laser treatment for clinically significant diabetic macular oedema
      demonstrated significant visual gain and CRT reduction after bevacizumab
      treatment and stabilisation after navigated laser up to 12 months. The number of
      injections required in 12 months was lower than reported in previous combination
      studies.

PMID- 24723618
TI  - HIV and sexually transmitted infection-related risks among female sex workers in
      Mongolia: second-generation surveillance survey, 2011-2012.
AB  - BACKGROUND: Surveillance studies among female sex workers (FSWs) in Mongolia have
      found no HIV but high rates of syphilis, ranging from 10.7% in 2002 to 20.8% in
      2007. OBJECTIVES: To determine the current prevalence of HIV and syphilis among
      FSWs, and to identify syphilis risk factors. METHODS: 761 FSWs were recruited by
      time-location sampling between 2 January and 29 March 2012 in Ulaanbaatar city,
      Darkhan-Uul, Orkhon, Khuvsgul and Dornod provinces in Mongolia. Participants were
      administered an anonymous structured survey. Blood samples were tested for HIV
      and syphilis. Bivariate and multivariate logistic regression analyses were
      performed to identify factors associated with syphilis. RESULTS: The mean age of
      participants was 31 (median 30, interquartile range 24-38). HIV knowledge was
      modest: 41.3% correctly answered all questions. Consistent condom use with
      clients was reported by 49.1% of participants and exposure to HIV prevention
      programmes by 50.1%. Although no cases of HIV were found, syphilis prevalence was
      -27.8% (95% CI 24.3% to 31.7%). In multivariate analyses, variables associated
      with syphilis were younger age (age >30 years, OR=0.96, 95% CI 0.92 to 0.99) and
      occurrence of genital ulcer (OR=2.24, 95% CI 1.17 to 4.28). CONCLUSIONS: A
      syphilis epidemic continues to grow among FSWs in Mongolia. These women are at
      high risk of HIV transmission if introduced into their sexual networks. With the
      increase in migration of mining workers in Mongolia, introduction of HIV may be
      imminent. Efforts to intensify treatment and prevention programmes among FSWs are
      needed.

PMID- 24723617
TI  - Teleglaucoma: ready to go?
AB  - Telemedicine technologies and services allow today's ophthalmic clinicians to
      remotely diagnose, manage and monitor several ophthalmic conditions from a
      distance. But is this the case for glaucomas? There has been a proliferation of
      telemedicine friendly devices in recent years that improves the capabilities of
      the clinician in managing glaucomas. The existing instruments still need to align
      themselves with accepted industry standards. There are successful programmes
      running in several areas of the world. The safety and efficacy of these
      programmes needs further exploration. The inability of a single device or test to
      diagnose glaucomas satisfactorily has also hampered progress in remotely
      diagnosing these conditions. There is, however, significant potential for
      telemedicine-friendly devices to remotely monitor the progress of glaucoma and,
      thereby, reduce some of the workload on an overstretched health service. 

PMID- 24723619
TI  - The use of web-based diaries in sexual risk behaviour research: a systematic
      review.
AB  - BACKGROUND: An increasing number of studies have used the diary method, which
      provides quantitative event-level data about sexual encounters. Diaries are an
      attractive tool for sexual behaviour research, yet little is known about the
      range of uses, methodological issues and best practices associated with this
      technology. OBJECTIVES: To conduct a systematic review of the literature
      regarding the use of web-based diaries in sexual risk behaviour studies. DESIGN:
      Systematic review. DATA SOURCES: Five bibliographical databases, supplemented by
      references from previous reviews. METHODS: Eligible studies were published in
      English before August 2013, used the internet to transmit data from collection
      device to study staff, and measured behaviours affecting HIV or sexually
      transmitted infection transmission risk. The primary author conducted an initial
      screen to eliminate irrelevant articles. Both authors conducted full-text reviews
      to determine final articles. We abstracted data on diary methodology, validity
      and reactivity (behaviour change caused by diary completion). RESULTS: Twenty
      three articles representing 15 studies were identified. Most diaries were
      collected daily for 1 month via websites, and completion was generally high
      (>80%). Compensation varied by study and was not associated with completion.
      Studies comparing diary with retrospective survey data demonstrated evidence of
      over-reporting on retrospective tools, except for the least frequent behaviours.
      Most studies that assessed reactivity as a result of diary completion
      demonstrated some change in behaviour associated with frequent monitoring.
      CONCLUSIONS: Web-based diaries are an effective means of studying sexual risk
      behaviour. More uniform reporting and further research on the extent of
      reactivity are needed.

PMID- 24723620
TI  - Association of serum and vitreous concentrations of osteoprotegerin with diabetic
      retinopathy.
AB  - BACKGROUND: Angiogenesis is involved in the pathogenesis of diabetic retinopathy.
      Osteoprotegerin, a recently identified glycoprotein belonging to the tumour
      necrosis factor receptor superfamily, has been implicated to be correlated with
      angiogenesis. This study aims to determine whether serum and vitreous
      concentrations of osteoprotegerin are associated with diabetic retinopathy.
      METHODS: This study consisted of 254 diabetic patients (100 without diabetic
      retinopathy, 64 with non-proliferative diabetic retinopathy and 90 with
      proliferative diabetic retinopathy) and 62 control subjects. Serum and vitreous
      concentrations of osteoprotegerin were evaluated using enzyme-linked
      immunosorbent assay method. RESULTS: Serum and vitreous osteoprotegerin
      concentrations in proliferative diabetic retinopathy patients were significantly
      elevated compared with those of the other three groups. Non-proliferative
      diabetic retinopathy patients showed elevated concentrations of serum and
      vitreous osteoprotegerin compared with patients without diabetic retinopathy. In
      addition, control subjects had significantly lower serum and vitreous
      osteoprotegerin concentrations compared with diabetic patients without
      retinopathy, non-proliferative diabetic retinopathy patients and proliferative
      diabetic retinopathy patients. CONCLUSIONS: Serum and vitreous osteoprotegerin
      concentrations are associated with the presence and severity of diabetic
      retinopathy.

PMID- 24723621
TI  - Incidence of PR3- and MPO-ANCA autoantibody specificity changes in ANCA
      associated vasculitis.
AB  - BACKGROUND: Monitoring of anti-neutrophil cytoplasmic antibody (ANCA)-associated
      vasculitis (AAV) in remission usually includes indirect immunofluorescence (IIF),
      proteinase 3 (PR3)-ANCA and myeloperoxidase (MPO)-ANCA. Typically, PR3 and MPO
      ANCA are both performed because patients sometimes switch specificity during
      follow up. Published data are limited to case reports and incidence of change is
      not reported. The aim of this study was to quantify the incidence of antibody
      switching. METHODS: Hull and East Yorkshire Hospitals National Health Service
      Trust serves a population of 720,000 for ANCA testing. We reviewed all ANCA
      results from January 2000 to August 2012 to quantify incidence of antibody
      switching. A total of 22,002 IIF screens (14,518 patients) were performed. A
      total of 9838 (45%) also had PR3- and MPO-ANCA (6439, 44% of patients). Patients
      that changed specificity from PR3- to MPO-ANCA and vice versa were identified and
      case notes reviewed. RESULTS: A total of 218 patients with confirmed AAV positive
      for PR3/MPO-ANCA were followed for a mean of 2.6 years (range <0.1 to 12.4 years;
      with 113 (52%) patients followed for >1 year). Five patients (2%) changed
      specificity during follow up (3 GPA, 1 MPA & 1 EGPA). In two patients this was
      associated with relapse. Incidence of specificity change was 1 per 82 years
      (including two reversions to presenting specificity) and one per 286 years for
      changes associated with relapse. Monitoring using only the initial antibody
      specificity would have resulted in missed relapse in one patient. CONCLUSION:
      Antibody specificity changes in AAV are rare. Monitoring only the initial
      antibody specificity would have missed clinical events but rising C-reactive
      protein presaged relapse in these cases.

PMID- 24723622
TI  - From passive tool holders to microsurgeons: safer, smaller, smarter surgical
      robots.
AB  - Within only a few decades from its initial introduction, the field of surgical
      robotics has evolved into a dynamic and rapidly growing research area with
      increasing clinical uptake worldwide. Initially introduced for stereotaxic
      neurosurgery, surgical robots are now involved in an increasing number of
      procedures, demonstrating their practical clinical potential while propelling
      further advances in surgical innovations. Emerging platforms are also able to
      perform complex interventions through only a single-entry incision, and navigate
      through natural anatomical pathways in a tethered or wireless fashion. New
      devices facilitate superhuman dexterity and enable the performance of surgical
      steps that are otherwise impossible. They also allow seamless integration of
      microimaging techniques at the cellular level, significantly expanding the
      capabilities of surgeons. This paper provides an overview of the significant
      achievements in surgical robotics and identifies the current trends and future
      research directions of the field in making surgical robots safer, smaller, and
      smarter. 

PMID- 24723623
TI  - Variable Ventilation as a Diagnostic Tool for the Injured Lung.
AB  - Mechanical ventilation of patients with acute respiratory distress syndrome
      (ARDS) is a necessary life support measure which may lead to ventilator-induced
      lung injury, a complication that can be reduced or ameliorated by using
      appropriate tidal volumes and positive end-expiratory pressures. However, the
      optimal mechanical ventilation parameters are almost certainly different for each
      patient, and will vary with time as the injury status of the lung changes. In
      order to optimize mechanical ventilation in an individual ARDS patient,
      therefore, it is necessary to track the manner in which injury status is
      reflected in the mechanical properties of the lungs. Accordingly, we developed an
      algorithm for assessing the time-dependent manner in which different lung regions
      open (recruit) and close (derecruit) as a function of the pressure waveform that
      is applied to the airways during mechanical ventilation. We used this algorithm
      to test the notion that variable ventilation provides the dynamic perturbations
      in lung volume necessary to accurately identify recruitment/derecruitment
      dynamics in the injured lung. We performed this test on synthetic pressure and
      flow data generated with established numerical models of lung function
      corresponding to both healthy mice and mice with lung injury. The data were
      generated by subjecting the models to a variety of mechanical ventilation
      regimens including variable ventilation. Our results support the hypothesis that
      variable ventilation can be used as a diagnostic tool to identify the injury
      status of the lung in ARDS. 

PMID- 24723624
TI  - Volumetric quantification of airway wall in CT via collision-free active surface
      model: application to asthma assessment.
AB  - Emerging idea in asthma phenotyping, incorporating local morphometric information
      on the airway wall thickness would be able to better account for the process of
      airway remodeling as indicator of pathology or therapeutic impact. It is thus
      important that such information be provided uniformly along the airway tree, not
      on a sparse (cross-section) sampling basis. The volumetric segmentation of the
      airway wall from CT data is the issue addressed in this paper by exploiting a
      patient-specific surface active model. An original aspect taken into account in
      the proposed deformable model is the management of auto-collisions for this
      complex morphology. The analysis of several solutions ended up with the design of
      a motion vector field specific to the patient geometry to guide the deformation.
      The segmentation result, presented as two embedded inner/outer surfaces of the
      wall, allows the quantification of the tissue thickness based on a locally
      defined measure sensitive to even small surface irregularities. The method is
      validated with respect to several ground truth simulations of pulmonary CT data
      with different airway geometries and acquisition protocols showing accuracy
      within the CT resolution range. Results from an ongoing clinical study on
      moderate and severe asthma are presented and discussed. 

PMID- 24723625
TI  - A fuzzy-rule-based approach for single frame super resolution.
AB  - In this paper, a novel fuzzy rule-based prediction framework is developed for
      high-quality image zooming. In classical interpolation-based image zooming,
      resolution is increased by inserting pixels using certain interpolation
      techniques. Here, we propose a patch-based image zooming technique, where each
      low-resolution (LR) image patch is replaced by an estimated high-resolution (HR)
      patch. Since an LR patch can be generated from any of the many possible HR
      patches, it would be natural to develop rules to find different possible HR
      patches and then to combine them according to rule strength to get the estimated
      HR patch. Here, we generate a large number of LR-HR patch pairs from a collection
      of natural images, group them into different clusters, and then generate a fuzzy
      rule for each of these clusters. The rule parameters are also learned from these
      LR-HR patch pairs. As a result, an efficient mapping from LR patch space to HR
      patch space can be formulated. The performance of the proposed method is tested
      on different images, and is also compared with other representative as well as
      state-of-the-art image zooming techniques. Experimental results show that the
      proposed method is better than the competing methods and is capable of
      reconstructing thin lines, edges, fine details, and textures in the image
      efficiently.

PMID- 24723626
TI  - Common feature discriminant analysis for matching infrared face images to optical
      face images.
AB  - In biometrics research and industry, it is critical yet a challenge to match
      infrared face images to optical face images. The major difficulty lies in the
      fact that a great discrepancy exists between the infrared face image and
      corresponding optical face image because they are captured by different devices
      (optical imaging device and infrared imaging device). This paper presents a new
      approach called common feature discriminant analysis to reduce this great
      discrepancy and improve optical-infrared face recognition performance. In this
      approach, a new learning-based face descriptor is first proposed to extract the
      common features from heterogeneous face images (infrared face images and optical
      face images), and an effective matching method is then applied to the resulting
      features to obtain the final decision. Extensive experiments are conducted on two
      large and challenging optical-infrared face data sets to show the superiority of
      our approach over the state-of-the-art. 

PMID- 24723627
TI  - Derivative-based scale invariant image feature detector with error resilience.
AB  - We present a novel scale-invariant image feature detection algorithm (D-SIFER)
      using a newly proposed scale-space optimal 10th-order Gaussian derivative (GDO
      10) filter, which reaches the jointly optimal Heisenberg's uncertainty of its
      impulse response in scale and space simultaneously (i.e., we minimize the maximum
      of the two moments). The D-SIFER algorithm using this filter leads to an
      outstanding quality of image feature detection, with a factor of three quality
      improvement over state-of-the-art scale-invariant feature transform (SIFT) and
      speeded up robust features (SURF) methods that use the second-order Gaussian
      derivative filters. To reach low computational complexity, we also present a
      technique approximating the GDO-10 filters with a fixed-length implementation,
      which is independent of the scale. The final approximation error remains far
      below the noise margin, providing constant time, low cost, but nevertheless high
      quality feature detection and registration capabilities. D-SIFER is validated on
      a real-life hyperspectral image registration application, precisely aligning up
      to hundreds of successive narrowband color images, despite their strong artifacts
      (blurring, low-light noise) typically occurring in such delicate optical system
      setups.

PMID- 24723628
TI  - Activity and views of service users involved in mental health research: UK
      survey.
AB  - BACKGROUND: Optimisation of the process and outcomes of service user involvement
      in research is dependent on understanding current practice, challenges and
      opportunities. AIMS: To describe activities, roles and experiences of service
      users involved in mental health research. METHOD: National cross-sectional online
      questionnaire survey, using snowball sampling. Descriptive statistics and
      framework analysis undertaken collaboratively with a service user reference
      group. RESULTS: The survey revealed a previously undescribed, highly qualified
      service user research workforce. Positioned within and alongside mainstream
      research, respondents reported drawing on extensive service use, and passion for
      service improvement to challenge perceived clinical academic dominance of
      research. The support of peers was crucial to involvement, which typically
      enhanced mental health but for some, pervasive stigma and scrutiny undermined
      self-confidence and practical difficulties challenged equitable participation.
      CONCLUSIONS: Recognition of the service user research workforce will support the
      constructive amalgamation of academic and experiential expertise needed to shape
      and realise investment in mental health research.

PMID- 24723629
TI  - Psychiatric resilience: longitudinal twin study.
AB  - BACKGROUND: The source of variability in people's response to stressful life
      events is poorly understood. AIMS: We examine the genetic and environmental
      underpinning of resilience (i.e. the difference between the twins' internalising
      symptoms and their predicted symptoms based on cumulative stressful life events).
      METHOD: Stressful life event exposure and internalising symptoms were assessed at
      two time points in 7500 adult twins. Using the residual between actual and
      predicted internalising symptom total score, twin modelling was conducted for
      each wave separately and longitudinally. RESULTS: Resilience was found to have a
      moderate genetic heritability at each wave (~31%). Qualitative gender effects
      were found. Incorporating error of measurement into the model increased the
      estimated heritability for the latent construct of resilience (~50%). When
      measurement error and occasion-specific effects were removed, environmental
      influences contributed roughly equally to level of resilience. CONCLUSIONS: Both
      genes and environment influence level of psychiatric resilience, and are largely
      stable over time. Environmental influences can have an enduring effect on
      resilience.

PMID- 24723630
TI  - Insight, duration of untreated psychosis and attachment in first-episode
      psychosis: prospective study of psychiatric recovery over 12-month follow-up.
AB  - BACKGROUND: Increasing evidence shows attachment security influences symptom
      expression and adaptation in people diagnosed with schizophrenia and other
      psychoses. AIMS: To describe the distribution of secure and insecure attachment
      in a cohort of individuals with first-episode psychosis, and to explore the
      relationship between attachment security and recovery from positive and negative
      symptoms in the first 12 months. METHOD: The study was a prospective 12-month
      cohort study. The role of attachment, duration of untreated psychosis (DUP),
      baseline symptoms and insight in predicting and mediating recovery from symptoms
      was investigated using multiple regression analysis and path analysis. RESULTS:
      Of the 79 participants, 54 completed the Adult Attachment Interview (AAI): 37
      (68.5%) were classified as insecure, of which 26 (48.1%) were insecure/dismissing
      and 11 (20.4%) insecure preoccupied. Both DUP and insight predicted recovery from
      positive symptoms at 12 months. Attachment security, DUP and insight predicted
      recovery from negative symptoms at 12 months. CONCLUSIONS: Attachment is an
      important construct contributing to understanding and development of
      interventions promoting recovery following first-episode psychosis.

PMID- 24723631
TI  - First-contact incidence of psychosis in north-eastern Italy: influence of age,
      gender, immigration and socioeconomic deprivation.
AB  - BACKGROUND: Considerable variations in the incidence of psychosis have been
      observed across countries, in terms of age, gender, immigration status,
      urbanicity and socioeconomic deprivation. AIMS: To evaluate the incidence rate of
      first-episode psychosis in a large area of north-eastern Italy and the
      distribution of the above-mentioned risk factors in individuals with psychoses.
      METHOD: Epidemiologically based survey. Over a 3-year period individuals with
      psychosis on first contact with services were identified and diagnosed according
      to ICD-10 criteria. RESULTS: In total, 558 individuals with first-episode
      psychosis were identified during 3,077,555 person-years at risk. The annual
      incidence rate per 100,000 was 18.1 for all psychoses, 14.3 for non-affective
      psychoses and 3.8 for affective psychoses. The rate for all psychoses was higher
      in young people aged 20-29 (incidence rate ratio (IRR) = 4.18, 95% CI 2.77-6.30),
      immigrants (IRR = 2.26, 95% CI 1.85-2.75) and those living in the most deprived
      areas (IRR = 2.09, 95% CI 1.54-2.85). CONCLUSIONS: The incidence rate in our
      study area was lower than that found in other European and North American studies
      and provides new insights into the factors that may increase and/or decrease risk
      for developing psychosis.

PMID- 24723632
TI  - Adaptive spatio-temporal filtering for movement related potentials in EEG-based
      brain-computer interfaces.
AB  - Movement related potentials (MRPs) are used as features in many brain-computer
      interfaces (BCIs) based on electroencephalogram (EEG). MRP feature extraction is
      challenging since EEG is noisy and varies between subjects. Previous studies used
      spatial and spatio-temporal filtering methods to deal with these problems.
      However, they did not optimize temporal information or may have been susceptible
      to overfitting when training data are limited and the feature space is of high
      dimension. Furthermore, most of these studies manually select data windows and
      low-pass frequencies. We propose an adaptive spatio-temporal (AST) filtering
      method to model MRPs more accurately in lower dimensional space. AST
      automatically optimizes all parameters by employing a Gaussian kernel to
      construct a low-pass time-frequency filter and a linear ridge regression (LRR)
      algorithm to compute a spatial filter. Optimal parameters are simultaneously
      sought by minimizing leave-one-out cross-validation error through gradient
      descent. Using four BCI datasets from 12 individuals, we compare the performances
      of AST filter to two popular methods: the discriminant spatial pattern filter and
      regularized spatio-temporal filter. The results demonstrate that our AST filter
      can make more accurate predictions and is computationally feasible. 

PMID- 24723633
TI  - Compact low-power cortical recording architecture for compressive multichannel
      data acquisition.
AB  - This paper introduces an area- and power-efficient approach for compressive
      recording of cortical signals used in an implantable system prior to
      transmission. Recent research on compressive sensing has shown promising results
      for sub-Nyquist sampling of sparse biological signals. Still, any large-scale
      implementation of this technique faces critical issues caused by the increased
      hardware intensity. The cost of implementing compressive sensing in a
      multichannel system in terms of area usage can be significantly higher than a
      conventional data acquisition system without compression. To tackle this issue, a
      new multichannel compressive sensing scheme which exploits the spatial sparsity
      of the signals recorded from the electrodes of the sensor array is proposed. The
      analysis shows that using this method, the power efficiency is preserved to a
      great extent while the area overhead is significantly reduced resulting in an
      improved power-area product. The proposed circuit architecture is implemented in
      a UMC 0.18 [Formula: see text]m CMOS technology. Extensive performance analysis
      and design optimization has been done resulting in a low-noise, compact and power
      efficient implementation. The results of simulations and subsequent
      reconstructions show the possibility of recovering fourfold compressed
      intracranial EEG signals with an SNR as high as 21.8 dB, while consuming 10.5
      [Formula: see text]W of power within an effective area of 250 [Formula: see
      text]m * 250 [Formula: see text]m per channel. 

PMID- 24723634
TI  - Epsilon-tube filtering: reduction of high-amplitude motion artifacts from
      impedance plethysmography signal.
AB  - The impedance plethysmography (IP) has long been used to monitor respiration. The
      IP signal is also suitable for portable monitoring of respiration due to its
      simplicity. However, this signal is very susceptible to motion artifact (MA). As
      a result, MA reduction is an indispensable part of portable acquisition of the IP
      signal. Often, the amplitude of the MA is much larger than the amplitude of the
      respiratory component in the IP signal. This study proposes a novel filtering
      method to remove the high-amplitude MA's from the IP signal. The proposed method
      combines the idea of epsilon-tube loss function and an autoregressive exogenous
      model to estimate the MA while leaving the periodic respiratory component of the
      IP signal intact. Also, a regularization method is used to find the best filter
      coefficients that maximize the regularity of the output signal. The results
      indicate that the proposed method can effectively remove the MA, outperforming
      the popular MA reduction methods. Several different performance measures are used
      for the comparison and the differences are found to be statistically significant.

PMID- 24723635
TI  - Tolerance induction in hypersensitivity reactions from drugs: a brief overview.
AB  - Drug hypersensitivity reactions can occur with many drugs, are unpredictable, may
      affect any organ system and range widely in clinical severity from mild pruritus
      to exanthems to anaphylaxis. In most cases, the suspected drug must be avoided in
      the future. However, for certain patients, the particular drug may be essential
      for an optimal therapy. Under these circumstances, desensitization may be
      performed. 

PMID- 24723636
TI  - A systematic review of concussion in rugby league.
AB  - OBJECTIVES: Concussion remains one of the inherent risks of participation in
      rugby league. While other injuries incurred by rugby league players have been
      well studied, less focus and attention has been directed towards concussion.
      REVIEW METHOD: The current review examined all articles published in English from
      1900 up to June 2013 pertaining to concussion in rugby league players. DATA
      SOURCES: Publications were retrieved via six databases using the key search
      terms: rugby league, league, football; in combination with injury terms: athletic
      injuries, concussion, sports concussion, sports-related concussion, brain
      concussion, brain injury, brain injuries, mild traumatic brain injury, mTBI,
      traumatic brain injury, TBI, craniocerebral trauma, head injury and brain damage.
      Observational, cohort, correlational, cross-sectional and longitudinal studies
      were all included. RESULTS: 199 rugby league injury publications were identified.
      39 (20%) were related in some way to concussion. Of the 39 identified articles, 6
      (15%) had the main aim of evaluating concussion, while the other 33 reported on
      concussion incidence as part of overall injury data analyses. Rugby league
      concussion incidence rates vary widely from 0.0 to 40.0/1000 playing hours,
      depending on the definition of injury (time loss vs no time loss). The incidence
      rates vary across match play versus training session, seasons (winter vs summer)
      and playing position (forwards vs backs). The ball carrier has been found to be
      at greater risk for injury than tacklers. Concussion accounts for 29% of all
      injuries associated with illegal play, but only 9% of injuries sustained in legal
      play. CONCLUSIONS: In comparison with other collision sports, research evaluating
      concussion in rugby league is limited. With such limited published rugby league
      data, there are many aspects of concussion that require attention, and future
      research may be directed towards these unanswered questions.

PMID- 24723637
TI  - Are we currently underestimating the risk of scrum-related neck injuries in rugby
      union front-row players?

PMID- 24723647
TI  - Update of the European guidelines for basal cell carcinoma management.
AB  - BACKGROUND: European guidelines for the management of basal cell carcinoma (BCC)
      prepared by the former BCC subcommittee of the Guidelines Committee of the
      European Dermatology Forum (EDF) were published in 2006. OBJECTIVES: To present
      updated guidelines that include consensual expert definitions on various BCC
      types, prognosis and risk factors for BCC as well as review recommendations for
      diagnosis and treatment reflecting current published evidence. METHODS: These
      guidelines (S1 type) were prepared by the new BCC subgroup of the European
      Dermatology Forum (EDF)'s Guidelines Committee through extensive literature
      review (up to 2012) and expert experience; they were extensively discussed within
      the EDF subcommittee and approved by peer reviewers of the EDF. Results BCC is a
      common tumour with an incidence rising worldwide. Three major clinical types of
      BCC are recognized: nodular, superficial and morpheaform. Four histological
      subtypes are defined: superficial, nodular, infiltrative and morpheaform. On the
      basis of the risk of relapse, three prognosis groups have been identified: high,
      intermediate and low risk. According to these classifications and evidence-based
      evaluation of the therapeutic strategies available, a decision tree is proposed
      for the management of BCCs. CONCLUSIONS: The guidelines offer a useful tool that
      will help dermatologists to select the most appropriate treatment for individual
      patients.

PMID- 24723648
TI  - A rare case of pigmented epithelioid melanocytoma on the penis as a divided
      nevus.

PMID- 24723649
TI  - Treatment of non-episodic angioedema associated with eosinophilia with suplatast
      tosilate, an anti-allergic selective Th2 cytokine inhibitor.

PMID- 24723650
TI  - Examination of skin lesions for cancer: which clinical decision aids and tools
      are available in general practice?
AB  - BACKGROUND: While skin cancer incidence is rising throughout Europe, general
      practitioners (GP) feel unsure about their ability to diagnose skin malignancies.
      Objectives To evaluate whether the GP has sufficient validated clinical decision
      aids and tools for the examination of potentially malignant skin lesions.
      METHODS: We conducted a review searching Medline and the Cochrane Library. In
      addition, reference lists and personal archives were examined. Outcome measures
      were sensitivity and specificity but also the advantages and disadvantages of
      different clinical decision aids and tools. RESULTS: No clinical decision aids or
      tools for the examination of non-pigmented lesions are available. Clinical
      decision aids and tools for the examination of pigmented lesions have mostly been
      studied in secondary care and, in primary care, randomised clinical trials
      comparing the additional value of a clinical decision aid or tools to care are
      scarce. CONCLUSION: Sufficiently validated clinical decision aids and tools for
      the examination of potentially malignant skin lesions are lacking in general
      practice. The clinical decision aids and tools available in primary care need to
      be studied.

PMID- 24723651
TI  - Recurrent angioedema: diagnosis strategy and biological aspects.
AB  - The aetiologies of recurrent angioedema (AE) comprise the frequent histaminergic
      AE and the rare bradykinin-mediated AE. Diagnosis must be done carefully because
      they do not have the same treatment. Diagnosis strategy is clinical. The most
      specific symptoms for bradykinin AE are: isolated AE without wheals, long
      duration of the attack, abdominal localisation. The unique useful biological
      tests for the diagnosis of bradykinin AE are C1Inh exploration which is altered
      in hereditary AE (HAE) types I and II. No other biological test is useful in
      clinical practice at present. In case of suspicion of bradykinin AE with normal
      C1Inh, physicians must think of drug-induced AE. Hereditary AE with normal C1Inh
      may be associated with a mutation on gene F12 in 20% of cases. For 80% of
      patients without mutation, the diagnosis must be done very carefully. 

PMID- 24723652
TI  - PROMETHEUS and POSEIDON: Harnessing the power of advanced cardiac imaging.

PMID- 24723653
TI  - Positive feedback in cardioprotection: can more mechanism lead to translation?

PMID- 24723654
TI  - Metabolic flux as a predictor of heart failure prognosis.
AB  - The creatine kinase (CK) system is thought to play an integral role in
      maintaining levels of chemical energy in the form of ATP, which is essential for
      normal cardiac function. In the failing heart, it has long been established that
      multiple components of CK energy metabolism are commonly impaired and that these
      correlate with disease severity. A recent study published in Science
      Translational Medicine adds significantly to this body of evidence by
      demonstrating that the rate of ATP transfer via CK, measured noninvasively by
      magnetic resonance spectroscopy, is an independent predictor of adverse clinical
      outcome in patients with nonischemic cardiomyopathy. This finding invites
      speculation on the future role of metabolic imaging for risk stratification in
      patients with heart failure. The authors further assert an implied causal role
      for energetics in disease progression. Although this is not supported by recent
      findings in loss-of-function mouse models, there is, nonetheless, a strong
      argument for the development of novel metabolic therapies for the failing heart.

PMID- 24723655
TI  - How to write a successful grant application and research paper.

PMID- 24723656
TI  - Role of RyR2 phosphorylation in heart failure and arrhythmias: Controversies
      around ryanodine receptor phosphorylation in cardiac disease.
AB  - Cardiac ryanodine receptor type 2 plays a key role in excitation-contraction
      coupling. The ryanodine receptor type 2 channel protein is modulated by various
      post-translational modifications, including phosphorylation by protein kinase A
      and Ca(2+)/calmodulin protein kinase II. Despite extensive research in this area,
      the functional effects of ryanodine receptor type 2 phosphorylation remain
      disputed. In particular, the potential involvement of increased ryanodine
      receptor type 2 phosphorylation in the pathogenesis of heart failure and
      arrhythmias remains a controversial area, which is discussed in this review
      article.

PMID- 24723657
TI  - Role of RyR2 phosphorylation in heart failure and arrhythmias: protein kinase A
      mediated hyperphosphorylation of the ryanodine receptor at serine 2808 does not
      alter cardiac contractility or cause heart failure and arrhythmias.
AB  - This Controversies in Research article discusses the hypothesis that protein
      kinase A (PKA)-mediated phosphorylation of the Ryanodine Receptor (RyR) at a
      single serine (RyRS2808) is essential for normal sympathetic regulation of
      cardiac myocyte contractility and is responsible for the disturbed Ca(2+)
      regulation that underlies depressed contractility in heart failure. Studies
      supporting this hypothesis have associated hyperphosphorylation of RyRS2808 and
      heart failure progression in animals and humans and have shown that a
      phosphorylation defective RyR mutant mouse (RyRS2808A) does not respond normally
      to sympathetic agonists and does not exhibit heart failure symptoms after
      myocardial infarction. Studies to confirm and extend these ideas have failed to
      support the original data. Experiments from many different laboratories have
      convincingly shown that PKA-mediated RyRS2808 phosphorylation does not play any
      significant role in the normal sympathetic regulation of sarcoplasmic reticulum
      Ca2+ release or cardiac contractility. Hearts and myocytes from RyRS2808A mice
      have been shown to respond normally to sympathetic agonists, and to increase
      Ca(2+) influx, Ca(2+) transients, and Ca(2+) efflux. Although the RyR is involved
      in heart failure-related Ca(2+) disturbances, this results from Ca(2+)-calmodulin
      kinase II and reactive oxygen species-mediated regulation rather than by RyR2808
      phosphorylation. Also, a new study has shown that RyRS2808A mice are not
      protected from myocardial infarction. Collectively, there is now a clear
      consensus in the published literature showing that dysregulated RyRs contribute
      to the altered Ca(2+) regulatory phenotype of the failing heart, but PKA-mediated
      phosphorylation of RyRS2808 has little or no role in these alterations.

PMID- 24723659
TI  - Unique metabolic features of stem cells, cardiomyocytes, and their progenitors.
AB  - Recently, growing attention has been directed toward stem cell metabolism, with
      the key observation that the plasticity of stem cells also reflects the
      plasticity of their energy substrate metabolism. There seems to be a clear link
      between the self-renewal state of stem cells, in which cells proliferate without
      differentiation, and the activity of specific metabolic pathways. Differentiation
      is accompanied by a shift from anaerobic glycolysis to mitochondrial respiration.
      This metabolic switch of differentiating stem cells is required to cover the
      energy demands of the different organ-specific cell types. Among other metabolic
      signatures, amino acid and carbohydrate metabolism is most prominent in
      undifferentiated embryonic stem cells, whereas the fatty acid metabolic signature
      is unique in cardiomyocytes derived from embryonic stem cells. Identifying the
      specific metabolic pathways involved in pluripotency and differentiation is
      critical for further progress in the field of developmental biology and
      regenerative medicine. The recently generated knowledge on metabolic key
      processes may help to generate mature stem cell-derived somatic cells for
      therapeutic applications without the requirement of genetic manipulation. In the
      present review, the literature about metabolic features of stem cells and their
      cardiovascular cell derivatives as well as the specific metabolic gene signatures
      differentiating between stem and differentiated cells are summarized and
      discussed. 

PMID- 24723661
TI  - Mass spectrometry for steroids.

PMID- 24723658
TI  - Induced pluripotent stem cells for post-myocardial infarction repair: remarkable
      opportunities and challenges.
AB  - Coronary artery disease with associated myocardial infarction continues to be a
      major cause of death and morbidity around the world, despite significant advances
      in therapy. Patients who have large myocardial infarctions are at highest risk
      for progressive heart failure and death, and cell-based therapies offer new hope
      for these patients. A recently discovered cell source for cardiac repair has
      emerged as a result of a breakthrough reprogramming somatic cells to induced
      pluripotent stem cells (iPSCs). The iPSCs can proliferate indefinitely in culture
      and can differentiate into cardiac lineages, including cardiomyocytes, smooth
      muscle cells, endothelial cells, and cardiac progenitors. Thus, large quantities
      of desired cell products can be generated without being limited by cellular
      senescence. The iPSCs can be obtained from patients to allow autologous therapy
      or, alternatively, banks of human leukocyte antigen diverse iPSCs are possible
      for allogeneic therapy. Preclinical animal studies using a variety of cell
      preparations generated from iPSCs have shown evidence of cardiac repair.
      Methodology for the production of clinical grade products from human iPSCs is in
      place. Ongoing studies for the safety of various iPSC preparations with regard to
      the risk of tumor formation, immune rejection, induction of arrhythmias, and
      formation of stable cardiac grafts are needed as the field advances toward the
      first-in-man trials of iPSCs after myocardial infarction.

PMID- 24723663
TI  - High risk for seizures following subarachnoid hemorrhage regardless of referral
      bias.
AB  - BACKGROUND: To investigate the frequency, predictors, and clinical impact of
      electrographic seizures in patients with high clinical or radiologic grade non
      traumatic subarachnoid hemorrhage (SAH), independent of referral bias. METHODS:
      We compared rates of electrographic seizures and associated clinical variables
      and outcomes in patients with high clinical or radiologic grade non-traumatic
      SAH. Rates of electrographic seizure detection before and after institution of a
      guideline which made continuous EEG monitoring routine in this population were
      compared. RESULTS: Electrographic seizures occurred in 17.6 % of patients
      monitored expressly because of clinically suspected subclinical seizures. In
      unselected patients, seizures still occurred in 9.6 % of all cases, and in 8.6 %
      of cases in which there was no a priori suspicion of seizures. The first seizure
      detected occurred 5.4 (IQR 2.9-7.3) days after onset of subarachnoid hemorrhage
      with three of eight patients (37.5 %) having the first recorded seizure more than
      48 h following EEG initiation, and 2/8 (25 %) at more than 72 h following EEG
      initiation. High clinical grade was associated with poor outcome at time of
      hospital discharge; electrographic seizures were not associated with poor
      outcome. CONCLUSIONS: Electrographic seizures occur at a relatively high rate in
      patients with non-traumatic SAH even after accounting for referral bias. The
      prolonged time to the first detected seizure in this cohort may reflect dynamic
      clinical features unique to the SAH population.

PMID- 24723662
TI  - Imaging in forensic radiology: an illustrated guide for postmortem computed
      tomography technique and protocols.
AB  - Forensic radiology is a new subspecialty that has arisen worldwide in the field
      of forensic medicine. Postmortem computed tomography (PMCT) and, to a lesser
      extent, PMCT angiography (PMCTA), are established imaging methods that have
      replaced dated conventional X-ray images in morgues. However, these methods have
      not been standardized for postmortem imaging. Therefore, this article outlines
      the main approach for a recommended standard protocol for postmortem cross
      sectional imaging that focuses on unenhanced PMCT and PMCTA. This review should
      facilitate the implementation of a high-quality protocol that enables
      standardized reporting in morgues, associated hospitals or private practices that
      perform forensic scans to provide the same quality that clinical scans provide in
      court. 

PMID- 24723664
TI  - A simple framework for complex system improvement.
AB  - The need to rapidly improve health care value is unquestioned, but the means to
      accomplish this task is unknown. Improving performance at the level of the health
      care organization frequently involves multiple interventions, which must be
      coordinated and sequenced to fit the specific context. Those responsible for
      achieving large-scale improvements are challenged by the lack of a framework to
      describe and organize improvement strategies. Drawing from the fields of health
      services, industrial engineering, and organizational behavior, a simple framework
      was developed and has been used to guide and evaluate improvement initiatives at
      an academic health center. The authors anticipate that this framework will be
      helpful for health system leaders responsible for improving health care quality. 

PMID- 24723666
TI  - Calcium influx, but not intracellular calcium release, supports PACAP-mediated
      ERK activation in HEK PAC1 receptor cells.
AB  - In HEK cells expressing GFP-tagged PAC1Hop1 receptors, PACAP augments ERK
      phosphorylation through two parallel pathways: one through PACAP/PAC1 receptor
      internalization/endosome MEK/ERK signaling and the other through PLC/DAG/PKC
      activation. We examined whether elevation of intracellular calcium ([Ca(2+)]i)
      was required for either of the PACAP/PAC1 receptor-mediated ERK activation
      mechanisms. The PACAP (25 nM)-induced elevation of [Ca(2+)]i was greater with
      cells maintained in Ca(2+)-containing than in Ca(2+)-deficient solution,
      suggesting that both calcium release from internal stores and calcium influx
      contributed to the rise in [Ca(2+)]i. A thapsigargin-induced increase in
      [Ca(2+)]i also was greater with calcium in the external solution. OAG, the cell
      permeable analogue of DAG, increased [Ca(2+)]i, but only in Ca(2+)-containing
      solution. Decreasing external calcium or depleting internal calcium stores did
      not block PACAP-induced PAC1 receptor internalization. Omission of calcium from
      the external solution, but not thapsigargin pretreatment, significantly blunted
      PACAP-stimulated ERK phosphorylation. The PKC inhibitor BimI decreased PACAP
      mediated ERK activation in both Ca(2+)-containing or Ca(2+)-deficient solutions.
      In contrast, following Pitstop 2 pretreatment to block endocytic mechanisms,
      PACAP activated ERK only when calcium was present in the external solution. We
      conclude that the endosome signaling pathway is largely calcium-independent
      whereas calcium influx appears necessary for the PLC/DAG/PKC component of PACAP
      induced ERK activation. 

PMID- 24723665
TI  - PACAP application improves functional outcome of chronic retinal ischemic injury
      in rats-evidence from electroretinographic measurements.
AB  - Retinoprotective effects of pituitary adenylate cyclase activating polypeptide
      (PACAP) are well-known and have been demonstrated in various pathological
      conditions, such as diabetic retinopathy, excitotoxic retinal injury, UV light
      induced degeneration, and ischemic retinal lesion. The neuronal degeneration
      observed in the different retinal layers under the above pathological conditions
      can be successfully decreased by PACAP; however, whether this morphological
      improvement is also reflected in functional amelioration remains unknown.
      Therefore, our purpose was to investigate the protective effect of PACAP on the
      rat retina after bilateral common carotid artery occlusion (BCCAO) with
      electroretinography (ERG) to parallel the functional data with the previous
      morphological and neurochemical observations. Control eyes received saline
      treatment while PACAP was injected into the vitreous space of the other eye
      immediately after the induction of ischemia. Retinal damage and protective
      effects of PACAP were quantified by the changes in the wave forms and amplitudes.
      On postoperative days 2 and 14, several parameters were assessed with special
      attention to the changes of b wave. The results confirm that the previously
      described morphological protection induced by PACAP treatment is reflected in
      functional improvement in ischemic retinal lesions. 

PMID- 24723667
TI  - Dorsal approach to septum in external septorhinoplasty.
AB  - OBJECTIVE: During external septorhinoplasty, access from the caudal septum into
      subperichondrial space often poses difficulties and challenges for proper
      elevation of the mucoperichondrial flap. The dorsal and caudal approaches were
      compared with respect to duration and mucosal integrity. METHODS: The caudal
      approach was applied in 52 patients and the dorsal approach in 50 patients. The
      duration was recorded starting with septal incision, until the end of the
      completion of the bilateral subperichondrial and subperiosteal elevation. The
      mucosal integrity was inspected for any mucosal damage. RESULTS: The elevation
      durations for the caudal approach and the dorsal approach were 450.3 seconds and
      232 seconds, respectively. The impairment in mucosal integrity was observed in 33
      cases (63%) with the caudal approach and in 16 cases (32%) with the dorsal
      approach. Statistically significant differences were found between the 2 groups
      in terms of duration and mucosal integrity. CONCLUSION: The dorsal approach is a
      more advantageous choice that provides easier, safer, and faster access, ensures
      a comfortable and effective subperichondrial elevation, and is more advantageous
      for the protection of mucosal integrity as compared to the caudal approach from
      the anterior septal angle, since the perichondrium in the caudal septum is more
      attached to the underlying cartilage.

PMID- 24723668
TI  - Seasonal variations of plasma normetanephrine levels in Los Angeles.

PMID- 24723669
TI  - Seasonal variations of plasma normetaneprine levels: the authors reply.

PMID- 24723670
TI  - GEP-NETS update: functional localisation and scintigraphy in neuroendocrine
      tumours of the gastrointestinal tract and pancreas (GEP-NETs).
AB  - For patients with neuroendocrine tumours (NETs) of the gastrointestinal tract and
      pancreas (GEP) (GEP-NETs), excellent care should ideally be provided by a
      multidisciplinary team of skilled health care professionals. In these patients, a
      combination of nuclear medicine imaging and conventional radiological imaging
      techniques is usually mandatory for primary tumour visualisation, tumour staging
      and evaluation of treatment. In specific cases, as in patients with occult
      insulinomas, sampling procedures can provide a clue as to where to localise the
      insulin-hypersecreting pancreatic NETs. Recent developments in these fields have
      led to an increase in the detection rate of primary GEP-NETs and their metastatic
      deposits. Radiopharmaceuticals targeted at specific tumour cell properties and
      processes can be used to provide sensitive and specific whole-body imaging.
      Functional imaging also allows for patient selection for receptor-based therapies
      and prediction of the efficacy of such therapies. Positron emission
      tomography/computed tomography (CT) and single-photon emission CT/CT are used to
      map functional images with anatomical localisations. As a result, tumour imaging
      and tumour follow-up strategies can be optimised for every individual GEP-NET
      patient. In some cases, functional imaging might give indications with regard to
      future tumour behaviour and prognosis. 

PMID- 24723671
TI  - Cardiovascular magnetic resonance imaging for bicuspid aortic valve syndrome: the
      time is now.

PMID- 24723672
TI  - Carotid paraganglioma mimicking a cluster headache.

PMID- 24723673
TI  - Oxygen treatment of cluster headache: a review.
AB  - PURPOSE: Our aim was to review the existing literature to document oxygen's
      therapeutic effect on cluster headache. METHOD: A PubMed search resulted in 28
      hits, and from these and their references we found in total 11 relevant studies.
      We included six studies that investigated the efficacy of oxygen treatment. One
      study is observational and the remaining five are RCTs. Another five studies were
      on hyperbaric oxygen treatment hereof two case studies. CONCLUSION: Oxygen
      therapy can be administered at different flow rates. Three studies investigate
      the effect of low-flow oxygen, 6-7 l/min, and found a positive response in 56%,
      75% and 82%, respectively, of the patients. One study investigates high-flow
      oxygen, 12 l/min, and found efficacy in 78% of attacks. The effect of hyperbaric
      oxygen therapy has been investigated in a few small studies and there is evidence
      only for an acute, but not a prophylactic effect. Despite the fact that only a
      few high-quality RCT studies are available, oxygen treatment is close to an ideal
      treatment because it is effective and safe. However, sufferers of cluster
      headache do not always have access to oxygen because of logistic and financial
      concerns.

PMID- 24723674
TI  - Topiramate for migraine prevention in fertile women: reproductive counseling is
      warranted.

PMID- 24723675
TI  - Reversible cerebral vasoconstriction syndrome following indomethacin.
AB  - BACKGROUND: Reversible cerebral vasoconstriction syndrome (RCVS) is characterized
      by severe thunderclap headaches and transient segmental cerebral arterial
      vasoconstriction. Precipitating factors, including the postpartum state and
      exposure to vasoactive substances are identified in approximately 50% of cases.
      Non-steroidal anti-inflammatory drugs have rarely been associated with RCVS. CASE
      DESCRIPTION: We report a case of a 51-year-old female with RCVS after
      administration of indomethacin given to relieve pain caused by renal colic.
      Cerebral imaging showed non-aneurysmal cortical subarachnoid hemorrhage, and
      formal angiography demonstrated widespread multifocal segmental narrowing of
      medium-sized cerebral arteries. These changes resolved on repeat angiography at 3
      weeks. DISCUSSION: Indomethacin is a commonly used drug for treatment of certain
      primary headache disorders. To date, its mechanism of action remains unclear. A
      well described side effect of indomethacin is headache, which may be secondary to
      its vasoconstrictive effects. In our case, we postulate indomethacin, either
      alone or in combination with emotional stress from pain, triggered or exacerbated
      an underlying predisposition to RCVS.

PMID- 24723676
TI  - Sonic hedgehog causes mural cells to jump 'n' run.
AB  - In this issue of Blood, Yao and colleagues report that the morphogen sonic
      hedgehog (Shh) is driven by platelet-derived growth factor B (PDGF-BB) in
      vascular smooth muscle cells, contributing to vessel maturation in an autocrine
      manner.

PMID- 24723677
TI  - A WHIM satisfactorily addressed.
AB  - In this issue of Blood, McDermott et al present the intriguing, clinically
      relevant, and perhaps unexpected findings for the efficacy and safety of long
      term administration of low-dose plerixafor treatment of patients with warts,
      hypogammaglobulinemia, infections, and myelokathexis (WHIM) syndrome.

PMID- 24723678
TI  - FV and APC resistance: the plot thickens.
AB  - In this issue of Blood, Nogami et al report on a novel factor V (FV) gene
      mutation (FV Trp1920->Arg, FVNara) associated with activated protein C (APC)
      resistance and a severe thrombotic phenotype in a young Japanese patient. Since
      the affected amino acid residue is located in the light chain of FV, far from the
      known APC-cleavage sites, this discovery may afford new insights into the
      molecular mechanisms of APC resistance.

PMID- 24723679
TI  - Id2 represses E2A-mediated activation of IL-10 expression in T cells.
AB  - Interleukin-10 (IL-10) is a key immunoregulatory cytokine that functions to
      prevent inflammatory and autoimmune diseases. Despite the critical role for IL-10
      produced by effector CD8(+) T cells during pathogen infection and autoimmunity,
      the mechanisms regulating its production are poorly understood. We show that loss
      of the inhibitor of DNA binding 2 (Id2) in T cells resulted in aberrant IL-10
      expression in vitro and in vivo during influenza virus infection and in a model
      of acute graft-versus-host disease (GVHD). Furthermore, IL-10 overproduction
      substantially reduced the immunopathology associated with GVHD. We demonstrate
      that Id2 acts to repress the E2A-mediated trans-activation of the Il10 locus.
      Collectively, our findings uncover a key regulatory role of Id2 during effector T
      cell differentiation necessary to limit IL-10 production by activated T cells and
      minimize their suppressive activity during the effector phase of disease control.

PMID- 24723680
TI  - One siRNA pool targeting the lambda constant region stops lambda light-chain
      production and causes terminal endoplasmic reticulum stress.
AB  - In systemic light-chain amyloidosis, lambda light chains produced by clonal
      plasma cells cause organ damage and early death. In pursuit of novel therapy, we
      developed 1 pool of short interfering RNA (siRNA) targeting the constant region
      of lambda light chains that substantially and promptly reduces lambda-light-chain
      production and secretion by human plasma cells regardless of sequence diversity.
      In clones producing intact immunoglobulin G (IgG) lambda antibodies (containing
      paired heavy and light chains), the secretion of intact antibodies is reduced,
      and all 3 branches of the unfolded protein response are activated by accumulation
      of unpaired IgG heavy chains in the endoplasmic reticulum (ER). Moreover, an ER
      stress response can then become terminal with effector caspase activity mediated
      in part by the transcription of the Bcl-2 homology 3 domain only family member
      NOXA. This pool of siRNA can be used to reduce pathological lambda-light-chain
      production and cause apoptosis in human plasma cells making intact IgGlambda
      antibodies. 

PMID- 24723681
TI  - A TCR-mimic antibody to WT1 bypasses tyrosine kinase inhibitor resistance in
      human BCR-ABL+ leukemias.
AB  - Acute and chronic leukemias, including CD34(+) CML cells, demonstrate increased
      expression of the Wilms tumor gene 1 product (WT1), making WT1 an attractive
      therapeutic target. However, WT1 is a currently undruggable, intracellular
      protein. ESKM is a human IgG1 T-cell receptor mimic monoclonal antibody directed
      to a 9-amino acid sequence of WT1 in the context of cell surface HLA-A*02. ESKM
      was therapeutically effective, alone and in combination with tyrosine kinase
      inhibitors (TKIs), against Philadelphia chromosome-positive acute leukemia in
      murine models, including a leukemia with the most common, pan-TKI, gatekeeper
      resistance mutation, T315I. ESKM was superior to the first-generation TKI,
      imatinib. Combination therapy with ESKM and TKIs was superior to either drug
      alone, capable of curing mice. ESKM showed no toxicity to human HLA-A*02:01(+)
      stem cells under the conditions of this murine model. These features of ESKM make
      it a promising nontoxic therapeutic agent for sensitive and resistant Ph(+)
      leukemias. 

PMID- 24723683
TI  - Key challenges for next-generation pharmacogenomics: Science & Society series on
      Science and Drugs.

PMID- 24723682
TI  - TPL2 kinase regulates the inflammatory milieu of the myeloma niche.
AB  - Targeted modulation of microenvironmental regulatory pathways may be essential to
      control myeloma and other genetically/clonally heterogeneous cancers. Here we
      report that human myeloma-associated monocytes/macrophages (MAM), but not myeloma
      plasma cells, constitute the predominant source of interleukin-1beta (IL-1beta),
      IL-10, and tumor necrosis factor-alpha at diagnosis, whereas IL-6 originates from
      stromal cells and macrophages. To dissect MAM activation/cytokine pathways, we
      analyzed Toll-like receptor (TLR) expression in human myeloma CD14(+) cells. We
      observed coregulation of TLR2 and TLR6 expression correlating with local
      processing of versican, a proteoglycan TLR2/6 agonist linked to carcinoma
      progression. Versican has not been mechanistically implicated in myeloma
      pathogenesis. We hypothesized that the most readily accessible target in the
      versican-TLR2/6 pathway would be the mitogen-activated protein 3 (MAP3) kinase,
      TPL2 (Cot/MAP3K8). Ablation of Tpl2 in the genetically engineered in vivo myeloma
      model, Vkappa*MYC, led to prolonged disease latency associated with plasma cell
      growth defect. Tpl2 loss abrogated the "inflammatory switch" in MAM within
      nascent myeloma lesions and licensed macrophage repolarization in established
      tumors. MYC activation/expression in plasma cells was independent of Tpl2
      activity. Pharmacologic TPL2 inhibition in human monocytes led to dose-dependent
      attenuation of IL-1beta induction/secretion in response to TLR2 stimulation. Our
      results highlight a TLR2/6-dependent TPL2 pathway as novel therapeutic target
      acting nonautonomously through macrophages to control myeloma progression. 

PMID- 24723684
TI  - PICK1 links Argonaute 2 to endosomes in neuronal dendrites and regulates miRNA
      activity.
AB  - MicroRNAs fine-tune gene expression by inhibiting the translation of mRNA
      targets. Argonaute (Ago) proteins are critical mediators of microRNA-induced post
      transcriptional silencing and have been shown to associate with endosomal
      compartments, but the molecular mechanisms that underlie this process are
      unclear, especially in neurons. Here, we report a novel interaction between Ago2
      and the BAR-domain protein, PICK1. We show that PICK1 promotes Ago2 localization
      at endosomal compartments in neuronal dendrites and inhibits Ago2 function in
      translational repression following neuronal stimulation. We propose that PICK1
      provides a link between activity-dependent endosomal trafficking and local
      regulation of translation in neurons. 

PMID- 24723685
TI  - More than beef and tango: An interview with Lino Baranao, the Minister of
      Science, Technology and Productive Innovation in Argentina.

PMID- 24723686
TI  - The two-faced progeria gene and its implications in aging and metabolism.
AB  - Premature aging syndromes have gained much attention, not only because of their
      devastating symptoms but also because they might hold a key to some of the
      mechanisms underlying aging. The Hutchinson-Gilford progeria syndrome (HGPS) is
      caused by a mutation in the LMNA gene, which normally produces lamins A and C
      through alternative splicing. Due to this mutation, HGPS patients express an
      incompletely processed form of lamin A called progerin. In this issue of EMBO
      Reports, the Tazi group demonstrates how mice expressing different LMNA isoforms
      present opposite phenotypes in longevity, fat storage and mitochondrial function.

PMID- 24723687
TI  - New genes important for development.

PMID- 24723688
TI  - Revisiting "Is the scientific paper a fraud?": The way textbooks and scientific
      research articles are being used to teach undergraduate students could convey a
      misleading image of scientific research.

PMID- 24723689
TI  - Handling of patient data by Health and Social Care Information Centre is a
      "shambles," say MPs.

PMID- 24723691
TI  - The right of access to health care for undocumented migrants: a revision of
      comparative analysis in the European context.
AB  - BACKGROUND: The recent introduction of adjustment measures in the Spanish context
      by means of the Royal Decree-law 16/2012 (RDL 16/2012), which limits access to
      health care for undocumented migrants, raises the question about the state of the
      matter in different European Union member states. METHODS: Narrative review of
      comparative studies published between 2009 and 2012 that analyzes the right to
      health care for undocumented migrants in the European context. RESULTS: The
      review shows a high degree of variability regarding health care entitlements of
      undocumented migrants in different European countries, a frequent legal
      restriction of access to health care, as well as barriers in the effective access
      to health care. The studies coincide in recommending access at all health care
      levels, regardless of the administrative status of the person seeking treatment.
      The analysis of the impact of the current economic crisis on access and quality
      of the health care directed to undocumented migrants, as well as the knowledge of
      the migrants' perspective are identified as future research areas. CONCLUSIONS:
      Compared with other European countries, the introduction of the measures
      established in the RDL 16/2012 modifies the place of the Spanish Public Health
      Care System from being situated in the group of countries that permit
      undocumented migrants access to all health care levels, towards the category of
      highest restriction.

PMID- 24723690
TI  - Cultural adaptation and intervention integrity: a response to Skarstrand, Sundell
      and Andreasson.

PMID- 24723692
TI  - Resistance of naturally secreted alpha-synuclein to proteolysis.
AB  - Recent evidence suggests that specific extracellular alpha-synuclein (alpha-syn)
      strains are implicated in the progression of Parkinson's disease (PD) pathology.
      It is plausible that deregulation in the normal processing of secreted alpha-syn
      may be a causative risk factor for PD. To date, the degradation mechanisms
      involved have received very little attention. Here, we sought to investigate
      factors that regulate extracellular alpha-syn levels. We show, for the first
      time, that cell-secreted alpha-syn forms are resistant to direct proteolysis by
      kallikrein-related peptidase 6 (KLK6), an extracellular enzyme known to cleave
      recombinant alpha-syn. This differential susceptibility appears to be partially
      due to the association of secreted alpha-syn with lipids. We further provide
      evidence that secreted alpha-syn can be cleaved by KLK6 indirectly through
      activation of a secreted metalloprotease, suggestive of the involvement of a
      proteolytic cascade in the catabolism of secreted alpha-syn. Our results clearly
      suggest that physiological modifications affect the biochemical behavior of
      secreted alpha-syn and provide novel insights into mechanisms and potential
      targets for therapeutic interventions.-Ximerakis, M., Pampalakis, G.,
      Roumeliotis, T. I., Sykioti, V.-S., Garbis, S. D., Stefanis, L., Sotiropoulou,
      G., Vekrellis, K. Resistance of naturally secreted alpha-synuclein to
      proteolysis. 

PMID- 24723694
TI  - Vocal cord guides on neonatal endotracheal tubes.

PMID- 24723693
TI  - beta-Arrestin-1 mediates thyrotropin-enhanced osteoblast differentiation.
AB  - Thyrotropin (TSH) activation of the TSH receptor (TSHR), a 7-transmembrane
      spanning receptor (7TMR), may have osteoprotective properties by direct effects
      on bone. TSHR activation by TSH phosphorylates protein kinases AKT1, p38alpha,
      and ERK1/2 in some cells. We found TSH-induced phosphorylation of these kinases
      in 2 cell lines engineered to express TSHRs, human embryonic kidney HEK-TSHR
      cells and human osteoblastic U2OS-TSHR cells. In U2OS-TSHR cells, TSH up
      regulated pAKT1 (7.1+/-0.5-fold), p38alpha (2.9+/-0.4-fold), and pERK1/2 (3.1+/
      0.2-fold), whereas small molecule TSHR agonist C2 had no or little effect on
      pAKT1 (1.8+/-0.08-fold), p38alpha (1.2+/-0.09-fold), and pERK1/2 (1.6+/-0.19
      fold). Furthermore, TSH increased expression of osteoblast marker genes ALPL
      (8.2+/-4.6-fold), RANKL (21+/-5.9-fold), and osteopontin (OPN; 17+/-5.3-fold),
      whereas C2 had little effect (ALPL, 1.7+/-0.5-fold; RANKL, 1.3+/-0.6-fold; and
      OPN, 2.2+/-0.7-fold). beta-Arrestin-1 and -2 can mediate activatory signals by
      7TMRs. TSH stimulated translocation of beta-arrestin-1 and -2 to TSHR, whereas C2
      failed to translocate either beta-arrestin. Down-regulation of beta-arrestin-1 by
      siRNA inhibited TSH-stimulated phosphorylation of ERK1/2, p38alpha, and AKT1,
      whereas down-regulation of beta-arrestin-2 increased phosphorylation of AKT1 in
      both cell types and of ERK1/2 in HEK-TSHR cells. Knockdown of beta-arrestin-1
      inhibited TSH-stimulated up-regulation of mRNAs for OPN by 87 +/- 1.7% and RANKL
      by 73 +/- 2.4%, and OPN secretion by 74 +/- 10%. We conclude that TSH enhances
      osteoblast differentiation in U2OS cells that is, in part, caused by activatory
      signals mediated by beta-arrestin-1.

PMID- 24723695
TI  - Probiotics for preterm neonates: parents' perspectives and present prevalence.

PMID- 24723696
TI  - Perinatal regionalisation in the UK: an international perspective.

PMID- 24723697
TI  - Where should extreme preterm babies be delivered? Crucial data from EPICure.

PMID- 24723698
TI  - Retraction notice.

PMID- 24723699
TI  - Draft Genome Sequence of Phaeomoniella chlamydospora Strain RR-HG1, a Grapevine
      Trunk Disease (Esca)-Related Member of the Ascomycota.
AB  - The Ascomycota species Phaeomoniella chlamydospora, in concert with other fungi,
      is a causal agent for grapevine trunk diseases. Here, we present the first draft
      of the P. chlamydospora genome sequence, which comprises 355 scaffolds, with a
      total length of 26.59 Mb and 7,279 predicted protein-coding genes. 

PMID- 24723700
TI  - Draft Genome Sequence of Colletotrichum acutatum Sensu Lato (Colletotrichum
      fioriniae).
AB  - In addition to its economic impact, Colletotrichum acutatum sensu lato is an
      interesting model for molecular investigations due to the diversity of host
      determined specialization and reproductive lifestyles within the species complex.
      The pathogen Colletotrichum fioriniae forms part of this species complex and
      causes anthracnose in a wide range of crops and wild plants worldwide. Some
      members of this species have also been reported to be entomopathogenic. Here, we
      report the draft genome sequence of a heterothallic reference isolate of C.
      fioriniae (strain PJ7). This sequence provides a range of new resources that
      serve as a useful platform for further research in the field. 

PMID- 24723701
TI  - Lack of genetic diversity in newly sequenced porcine circovirus type 1 strains
      isolated 20 years apart.
AB  - The complete genome sequences of a porcine circovirus type 1 (PCV1) strain
      isolated in 1990 and one isolated in 2011 were obtained and compared to the
      sequences of other available PCV1 isolates. Phylogenetic analyses revealed very
      low genetic diversity among these viruses, indicating an advanced state in the
      evolution of PCV1. 

PMID- 24723702
TI  - Complete Genome Sequence of Staphylococcus aureus Phage GRCS.
AB  - The Staphylococcus aureus phage GRCS was isolated from a sewage treatment
      facility in India and has shown potential for phage therapy in a mouse model of
      bacteremia. Here, we report the complete genome sequence of this bacteriophage. 

PMID- 24723703
TI  - Draft Genome Sequence of the Aromatic Hydrocarbon-Degrading Bacterium Sphingobium
      sp. Strain Ant17, Isolated from Antarctic Soil.
AB  - Here, we present the draft genome sequence of Sphingobium sp. strain Ant17, an
      aromatic hydrocarbon-degrading bacterium that was isolated from Antarctic oil
      contaminated soil. An analysis of this genome can lead to insights into the
      mechanisms of xenobiotic degradation processes at low temperatures and
      potentially aid in bioremediation applications. 

PMID- 24723704
TI  - Complete Genome Sequence of Strain SDCV/USA/Illinois121/2014, a Porcine
      Deltacoronavirus from the United States.
AB  - To investigate the causative agent of swine diarrhea, next-generation sequencing
      (NGS) was performed on a porcine fecal sample. The NGS reads were assembled,
      which generated a complete swine Deltacoronavirus genome sequence, that of strain
      SDCV/USA/Illinois121/2014. 

PMID- 24723705
TI  - Draft Genome Sequences of Six Strains of Vibrio parahaemolyticus Isolated from
      Early Mortality Syndrome/Acute Hepatopancreatic Necrosis Disease Shrimp in
      Thailand.
AB  - Some strains of Vibrio parahaemolyticus cause acute hepatopancreatic necrosis
      disease (AHPND) in shrimp. We sequenced 3 AHPND and 3 non-AHPND strains and found
      that all of them lacked the pathogenicity island relevant to human infection. A
      unique sequence encoding a type IV pilus/type IV secretion system was found in 3
      AHPND strains. 

PMID- 24723706
TI  - Draft Genome Sequence of Magnetospirillum sp. Strain SO-1, a Freshwater
      Magnetotactic Bacterium Isolated from the Ol'khovka River, Russia.
AB  - Here, we present the draft genome sequence of Magnetospirillum sp. strain SO-1, a
      freshwater magnetotactic spirillum isolated from the sediments of the Ol'khovka
      River, Russia. 

PMID- 24723707
TI  - Complete Genome Sequences of Nitrofurantoin-Sensitive and -Resistant Escherichia
      coli ST540 and ST2747 Strains.
AB  - Widespread multidrug resistance in Escherichia coli has necessitated the
      reintroduction of older antibiotics, such as nitrofurantoin. However, mechanisms
      by which resistance to nitrofurantoin emerges in E. coli are not well elucidated.
      Toward this aim, we sequenced two nitrofurantoin-sensitive E. coli sequence types
      (ST540 and ST2747) and their four nitrofurantoin-resistant derivatives generated
      in vitro under aerobic and anaerobic growth conditions. 

PMID- 24723708
TI  - Genome Sequences of Foot-and-Mouth Disease Virus O/ME-SA/Ind-2001 Lineage from
      Outbreaks in Libya, Saudi Arabia, and Bhutan during 2013.
AB  - The complete genomes of foot-and-mouth disease (FMD) viruses recovered in Libya
      and Saudi Arabia in 2013 are described here. These viruses belong to an FMD virus
      lineage (Ind-2001, topotype Middle East-South Asia, serotype O) which is normally
      endemic in the Indian subcontinent. A contemporary virus sequence from Bhutan is
      also reported here. 

PMID- 24723709
TI  - Genome Sequence of Enterotoxigenic Escherichia coli Strain B2C.
AB  - Enterotoxigenic Escherichia coli (ETEC) is a major cause of diarrheal disease
      around the globe, causing an estimated 380,000 deaths annually. The disease is
      caused by a wide variety of strains. Here, we report the genome sequence of ETEC
      strain B2C, which was isolated from an American soldier in Vietnam. 

PMID- 24723710
TI  - Unique circovirus-like genome detected in pig feces.
AB  - Using a metagenomic approach and molecular cloning methods, we identified,
      cloned, and sequenced the complete genome of a novel circular DNA virus, porcine
      stool-associated virus (PoSCV4), from pig feces. Phylogenetic analysis of the
      deduced replication initiator protein showed that PoSCV4 is most related to a fur
      seal feces-associated circular DNA virus. 

PMID- 24723711
TI  - Complete genome sequences of a cytopathic/noncytopathic pair of border disease
      viruses.
AB  - The complete genome sequences of a cytopathic/noncytopathic pair of border
      disease viruses (BDV) that were isolated from a sheep with mucosal disease-like
      lesions were determined. The cytopathic virus possessed an insert of 288
      nucleotides that was derived from the Jiv cellular transcript and had 37
      nucleotide differences from the noncytopathic virus. 

PMID- 24723712
TI  - Draft Genome Sequence of Campylobacter ureolyticus Strain CIT007, the First Whole
      Genome Sequence of a Clinical Isolate.
AB  - Herein, we present the draft genome sequence of Campylobacter ureolyticus. Strain
      CIT007 was isolated from a stool sample from an elderly female presenting with
      diarrheal illness and end-stage chronic renal disease. 

PMID- 24723713
TI  - Genome Sequence of the Aerobic Arsenate-Reducing Bacterium Pantoea sp. Strain
      IMH.
AB  - We here report the draft assembly for the genome of Pantoea sp. strain IMH,
      isolated from arsenic-contaminated soil in Inner Mongolia, China, with the
      ability to aerobically reduce arsenate to arsenite. The genome sequence will
      allow for the characterization of the molecular mechanisms of arsenate reduction.

PMID- 24723714
TI  - Draft Genome Sequence of Methicillin-Resistant Staphylococcus aureus KT/Y21, a
      Sequence Type 772 (ST772) Strain Isolated from a Pediatric Blood Sample in
      Terengganu, Malaysia.
AB  - Here, we report the draft genome sequence of a methicillin-resistant
      Staphylococcus aureus (MRSA) strain, KT/Y21, isolated from a blood sample of a
      pediatric patient. This strain belongs to sequence type 772 (ST772), harbors the
      staphylococcal cassette chromosome mec element (SCCmec) type V, and is positive
      for the Panton-Valentine leukocidin (PVL) pathogenic determinant. 

PMID- 24723715
TI  - Whole-Genome Sequence of "Candidatus Liberibacter asiaticus" from Guangdong,
      China.
AB  - The draft genome sequence of "Candidatus Liberibacter asiaticus" strain A4,
      isolated from a mandarin citrus in Guangdong, People's Republic of China, is
      reported. The A4 strain has a genome size of 1,208,625 bp, G+C content of 36.4%,
      1,107 predicted open reading frames, and 53 RNA genes. 

PMID- 24723716
TI  - Draft Genome Sequence of Methanol-Utilizing Methylophilus sp. Strain OH31,
      Isolated from Pond Sediment in Hokkaido, Japan.
AB  - Methylophilus sp. strain OH31 was isolated from the sediment of the Ohno pond at
      Hokkaido University. Strain OH31 utilizes methanol as its energy source. Here, we
      present the draft genome sequence of Methylophilus sp. strain OH31. 

PMID- 24723717
TI  - Draft Genome Sequence of the Growth-Promoting Endophyte Paenibacillus sp. P22,
      Isolated from Populus.
AB  - Paenibacillus sp. P22 is a Gram-negative facultative anaerobic endospore-forming
      bacterium isolated from poplar hybrid 741 (?[Populus alba * (P. davidiana + P.
      simonii) * P. tomentosa]). This bacterium shows strong similarities to
      Paenibacillus humicus, and important growth-promoting effects on in vitro grown
      explants of poplar hybrid 741 have been described. 

PMID- 24723718
TI  - Full-Length Genome Sequence of Porcine Deltacoronavirus Strain USA/IA/2014/8734.
AB  - Porcine deltacoronavirus (PDCoV) was detected in feces from diarrheic sows during
      an epidemic of acute and transmissible diarrhea. No transmissible gastroenteritis
      virus or porcine epidemic diarrhea virus was detected. The PDCoV USA/IA/2014/8734
      from the herd was sequenced for full-length genomic RNA to further characterize
      PDCoV in U.S. swine. 

PMID- 24723719
TI  - Complete Genome Sequence of Paenibacillus polymyxa SQR-21, a Plant Growth
      Promoting Rhizobacterium with Antifungal Activity and Rhizosphere Colonization
      Ability.
AB  - Here we report the complete genome sequence of a plant growth-promoting
      rhizobacterium (PGPR), Paenibacillus polymyxa SQR-21, which consists of one
      circular chromosome of 5,828,438 bp with 5,024 coding sequences (CDS). The data
      presented highlight multiple sets of functional genes associated with its plant
      beneficial characteristics. 

PMID- 24723720
TI  - Draft Genome Sequences of Six Listeria monocytogenes Strains Isolated from Dairy
      Products from a Processing Plant in Southern Italy.
AB  - Here we announce the draft genome sequences of 6 Listeria monocytogenes strains
      from ricotta cheese produced in a dairy processing plant located in southern
      Italy and potentially involved in a multistate outbreak of listeriosis in the
      United States. 

PMID- 24723721
TI  - Genome Sequence of Bacterial Interference Strain Staphylococcus aureus 502A.
AB  - Staphylococcus aureus 502A was a strain used in bacterial interference programs
      during the 1960s and early 1970s. Infants were deliberately colonized with 502A
      with the goal of preventing colonization with more invasive strains. We present
      the completed genome sequence of this organism. 

PMID- 24723722
TI  - Draft genome sequences of the altered schaedler flora, a defined bacterial
      community from gnotobiotic mice.
AB  - The altered Schaedler flora (ASF) is a bacterial community that supports normal
      growth and development of gnotobiotic mice. We report here the draft genome
      sequences of the 8 bacteria that comprise the ASF. 

PMID- 24723723
TI  - Genome Sequence of Burkholderia cenocepacia H111, a Cystic Fibrosis Airway
      Isolate.
AB  - The Burkholderia cepacia complex (BCC) is a group of related bacterial species
      that are commonly isolated from environmental samples. Members of the BCC can
      cause respiratory infections in cystic fibrosis patients and immunocompromised
      individuals. We report here the genome sequence of Burkholderia cenocepacia H111,
      a well-studied model strain of the BCC. 

PMID- 24723724
TI  - Genome Sequence of the Salmonella enterica subsp. enterica Serovar Namur Strain
      05-2929, Lacking the Salmonella Atypical Fimbrial Operon.
AB  - This paper announces the genome sequence and annotation of Salmonella enterica
      subsp. enterica serovar Namur strain 05-2929. S. Namur is a new serovar
      (39:z4,z23:-) that was isolated from a patient with salmonellosis in 2005 in
      Namur, Belgium, and has been identified as lacking the Salmonella atypical
      fimbrial (saf) operon. 

PMID- 24723725
TI  - Genome and Transcriptome Sequences of Pseudomonas syringae pv. syringae B301D-R.
AB  - Strains of the plant pathogen Pseudomonas syringae are commonly found in the
      phylosphere and are able to infect a number of agriculturally important crops.
      Here, we report a high-quality draft genome sequence of Pseudomonas syringae pv.
      syringae B301D-R, isolated from pears, which is a model strain for phytotoxin
      research in P. syringae. 

PMID- 24723726
TI  - Complete Genome Sequence of Phodopus sungorus Papillomavirus Type 1 (PsPV1), a
      Novel Member of the Pipapillomavirus Genus, Isolated from a Siberian Hamster.
AB  - We report the complete genomic sequence of Phodopus sungorus papillomavirus type
      1 (PsPV1), isolated from an anogenital lesion of a Siberian hamster. PsPV1 is
      taxonomically classified in the genus Pipapillomavirus and is most closely
      related to Mesocricetus auratus papillomavirus 1 (MaPV1). 

PMID- 24723727
TI  - Draft Genome Sequence of Mycobacterium cosmeticum DSM 44829.
AB  - We announce the draft genome sequence of Mycobacterium cosmeticum strain DSM
      44829, a nontuberculous species responsible for opportunistic infection. The
      genome described here is composed of 6,462,090 bp, with a G+C content of 68.24%.
      It contains 6,281 protein-coding genes and 75 predicted RNA genes. 

PMID- 24723728
TI  - Genome evolution by matrix algorithms: cellular automata approach to population
      genetics.
AB  - Mammalian genomes are replete with millions of polymorphic sites, among which
      those genetic variants that are colocated on the same chromosome and exist close
      to one another form blocks of closely linked mutations known as haplotypes. The
      linkage within haplotypes is constantly disrupted due to meiotic recombination
      events. Whole ensembles of such numerous haplotypes are subjected to evolutionary
      pressure, where mutations influence each other and should be considered as a
      whole entity-a gigantic matrix, unique for each individual genome. This idea was
      implemented into a computational approach, named Genome Evolution by Matrix
      Algorithms (GEMA) to model genomic changes taking into account all mutations in a
      population. GEMA has been tested for modeling of entire human chromosomes. The
      program can precisely mimic real biological processes that have influence on
      genome evolution such as: 1) Authentic arrangements of genes and functional
      genomic elements, 2) frequencies of various types of mutations in different
      nucleotide contexts, and 3) nonrandom distribution of meiotic recombination
      events along chromosomes. Computer modeling with GEMA has demonstrated that the
      number of meiotic recombination events per gamete is among the most crucial
      factors influencing population fitness. In humans, these recombinations create a
      gamete genome consisting on an average of 48 pieces of corresponding parental
      chromosomes. Such highly mosaic gamete structure allows preserving fitness of
      population under the intense influx of novel mutations (40 per individual) even
      when the number of mutations with deleterious effects is up to ten times more
      abundant than those with beneficial effects.

PMID- 24723729
TI  - The genome of Cardinium cBtQ1 provides insights into genome reduction, symbiont
      motility, and its settlement in Bemisia tabaci.
AB  - Many insects harbor inherited bacterial endosymbionts. Although some of them are
      not strictly essential and are considered facultative, they can be a key to host
      survival under specific environmental conditions, such as parasitoid attacks,
      climate changes, or insecticide pressures. The whitefly Bemisia tabaci is at the
      top of the list of organisms inflicting agricultural damage and outbreaks, and
      changes in its distribution may be associated to global warming. In this work, we
      have sequenced and analyzed the genome of Cardinium cBtQ1, a facultative
      bacterial endosymbiont of B. tabaci and propose that it belongs to a new
      taxonomic family, which also includes Candidatus Amoebophilus asiaticus and
      Cardinium cEper1, endosymbionts of amoeba and wasps, respectively. Reconstruction
      of their last common ancestors' gene contents revealed an initial massive gene
      loss from the free-living ancestor. This was followed in Cardinium by smaller
      losses, associated with settlement in arthropods. Some of these losses, affecting
      cofactor and amino acid biosynthetic encoding genes, took place in Cardinium
      cBtQ1 after its divergence from the Cardinium cEper1 lineage and were related to
      its settlement in the whitefly and its endosymbionts. Furthermore, the Cardinium
      cBtQ1 genome displays a large proportion of transposable elements, which have
      recently inactivated genes and produced chromosomal rearrangements. The genome
      also contains a chromosomal duplication and a multicopy plasmid, which harbors
      several genes putatively associated with gliding motility, as well as two other
      genes encoding proteins with potential insecticidal activity. As gene
      amplification is very rare in endosymbionts, an important function of these genes
      cannot be ruled out.

PMID- 24723730
TI  - Genome-wide analyses of a plant-specific LIM-domain gene family implicate its
      evolutionary role in plant diversification.
AB  - The Arabidopsis DA1 genes appear to have multiple functions in regulating organ
      size and abiotic stress response, but the biological roles of its closely related
      genes remain unknown. Evolutionary analyses might provide some clues to aid in an
      understanding of their functional diversification. In this work, we characterized
      the molecular evolution and expressional diversification of DA1-like genes.
      Surveying 354 sequenced genomes revealed 142 DA1-like genes only in plants,
      indicating plant-specificity of these genes. The DA1-like protein modular
      structure was composed of two UIMs (ubiquitin interaction motifs), one LIM-domain
      (from lin-11, isl-1, and mec-3), and a conserved C-terminal, and was
      distinguishable from the already defined three groups of LIM-domain proteins. We
      further found that the DA1-like genes diverged into Classes I and II at the
      ancestor of seed plants and acquired 13 clade-specific residues during their
      evolutionary history. Moreover, diverse intron size evolution was noted following
      the transition from size-expandable introns to minimal ones, accompanying the
      emergence and diversification of angiosperms. Functional diversification as it
      relates to gene expression was further investigated in soybean. Glycine max DA1
      genes showed diverse tissues expression patterns during development and had
      substantially varied abiotic stress response expression. Thus, variations in the
      coding regions, intron size, and gene expression contributed to the functional
      diversification of this gene family. Our data suggest that the evolution of the
      DA1-like genes facilitated the development of diverse molecular and functional
      diversification patterns to accompany the successful radiation of plants into
      diverse environments during evolution.

PMID- 24723732
TI  - A roadmap to understanding toll pathway changes: an educational primer for use
      with "regulation of toll signaling and inflammation by beta-arrestin and the SUMO
      protease Ulp1".
AB  - An article by Anjum et al. in the December 2013 issue of GENETICS can be used to
      illustrate reverse genetic manipulation in a model organism, targeted RNA
      interference, synergistic gene interaction, and biochemical regulation of gene
      expression using post-translational modification. This Primer provides background
      information, technical explanations of methods and genetic approaches from the
      study, an example approach for classroom use, and discussion questions to promote
      understanding of the research article.

PMID- 24723733
TI  - Disproportionate roles for the X chromosome and proteins in adaptive evolution.

PMID- 24723731
TI  - RNA sequencing and proteogenomics reveal the importance of leaderless mRNAs in
      the radiation-tolerant bacterium Deinococcus deserti.
AB  - Deinococcus deserti is a desiccation- and radiation-tolerant desert bacterium.
      Differential RNA sequencing (RNA-seq) was performed to explore the specificities
      of its transcriptome. Strikingly, for 1,174 (60%) mRNAs, the transcription start
      site was found exactly at (916 cases, 47%) or very close to the translation
      initiation codon AUG or GUG. Such proportion of leaderless mRNAs, which may
      resemble ancestral mRNAs, is unprecedented for a bacterial species. Proteomics
      showed that leaderless mRNAs are efficiently translated in D. deserti.
      Interestingly, we also found 173 additional transcripts with a 5'-AUG or 5'-GUG
      that would make them competent for ribosome binding and translation into novel
      small polypeptides. Fourteen of these are predicted to be leader peptides
      involved in transcription attenuation. Another 30 correlated with new gene
      predictions and/or showed conservation with annotated and nonannotated genes in
      other Deinococcus species, and five of these novel polypeptides were indeed
      detected by mass spectrometry. The data also allowed reannotation of the start
      codon position of 257 genes, including several DNA repair genes. Moreover,
      several novel highly radiation-induced genes were found, and their potential
      roles are discussed. On the basis of our RNA-seq and proteogenomics data, we
      propose that translation of many of the novel leaderless transcripts, which may
      have resulted from single-nucleotide changes and maintained by selective
      pressure, provides a new explanation for the generation of a cellular pool of
      small peptides important for protection of proteins against oxidation and thus
      for radiation/desiccation tolerance and adaptation to harsh environmental
      conditions.

PMID- 24723737
TI  - Evolution of advertisement calls in African clawed frogs.
AB  - For most frogs, advertisement calls are essential for reproductive success,
      conveying information on species identity, male quality, sexual state and
      location. While the evolutionary divergence of call characters has been examined
      in a number of species, the relative impacts of genetic drift or natural and
      sexual selection remain unclear. Insights into the evolutionary trajectory of
      vocal signals can be gained by examining how advertisement calls vary in a
      phylogenetic context. Evolution by genetic drift would be supported if more
      closely related species express more similar songs. Conversely, a poor
      correlation between evolutionary history and song expression would suggest
      evolution shaped by natural or sexual selection. Here, we measure seven song
      characters in 20 described and two undescribed species of African clawed frogs
      (genera Xenopus and Silurana) and four populations of X. laevis. We identify
      three call types - click, burst and trill - that can be distinguished by click
      number, call rate and intensity modulation. A fourth type is biphasic, consisting
      of two of the above. Call types vary in complexity from the simplest, a click, to
      the most complex, a biphasic call. Maximum parsimony analysis of variation in
      call type suggests that the ancestral type was of intermediate complexity. Each
      call type evolved independently more than once and call type is typically not
      shared by closely related species. These results indicate that call type is
      homoplasious and has low phylogenetic signal. We conclude that the evolution of
      call type is not due to genetic drift, but is under selective pressure.

PMID- 24723738
TI  - Flow over a membrane-covered, fluid-filled cavity.
AB  - The flow-induced response of a membrane covering a fluid-filled cavity located in
      a section of a rigid-walled channel was explored using finite element analysis.
      The membrane was initially aligned with the channel wall and separated the
      channel fluid from the cavity fluid. As fluid flowed over the membrane-covered
      cavity, a streamwise-dependent transmural pressure gradient caused membrane
      deformation. This model has application to synthetic models of the vocal fold
      cover layer used in voice production research. In this paper, the model is
      introduced and responses of the channel flow, the membrane, and the cavity flow
      are summarized for a range of flow and membrane parameters. It is shown that for
      high values of cavity fluid viscosity, the intracavity pressure and the beam
      deflection both reached steady values. For combinations of low cavity viscosity
      and sufficiently large upstream pressures, large-amplitude membrane vibrations
      resulted. Asymmetric conditions were introduced by creating cavities on opposing
      sides of the channel and assigning different stiffness values to the two
      membranes. The asymmetry resulted in reduction in or cessation of vibration
      amplitude, depending on the degree of asymmetry, and in significant skewing of
      the downstream flow field.

PMID- 24723739
TI  - Impact of serum biomarkers and clinical factors on intensive care unit mortality
      and 6-month outcome in relatively healthy patients with severe pneumonia and
      acute respiratory distress syndrome.
AB  - OBJECTIVES: This study aimed to identify the independent biomarkers and clinical
      factors that could predict ICU mortality and 6-month outcomes in relatively
      healthy patients with severe pneumonia and acute respiratory distress syndrome
      (ARDS). PATIENTS AND METHODS: We prospectively enrolled patients with severe
      pneumonia-related ARDS that required mechanical ventilation. Patients were
      excluded if they were unable to take care of themselves. Several biomarkers and
      clinical factors were evaluated prospectively on day 1 and day 3 after ICU
      admission. All biomarkers and clinical factors were collected for analysis.
      RESULTS: 56 patients were enrolled in this study. We determined that the initial
      appropriate antibiotics use was an independent clinical factor and day 1 high
      mobility group protein B1 (HMGB1) concentration was an independent biomarker for
      ICU mortality. Interestingly, we also found that a low day 1 albumin level was an
      independent biomarker for predicting patient life dependence 6 months after a
      pneumonia event. CONCLUSION: Patients with severe pneumonia and ARDS requiring
      mechanical ventilation experience high rates of ICU mortality or disability, even
      if they were quite healthy before. Initial appropriate antibiotics use and day 1
      level of HMGB1 were independent factors for predicting ICU mortality. Day 1
      albumin level was predictive of 6-month patient life dependence.

PMID- 24723740
TI  - Metabolomic Analysis of Liver Tissue from the VX2 Rabbit Model of Secondary Liver
      Tumors.
AB  - Purpose. The incidence of liver neoplasms is rising in USA. The purpose of this
      study was to determine metabolic profiles of liver tissue during early cancer
      development. Methods. We used the rabbit VX2 model of liver tumors (LT) and a
      control group consisting of sham animals implanted with Gelfoam into their livers
      (LG). After two weeks from implantation, liver tissue from lobes with and without
      tumor was obtained from experimental animals (LT+/LT-) as well as liver tissue
      from controls (LG+/LG-). Peaks obtained by Gas Chromatography-Mass Spectrometry
      were subjected to identification. 56 metabolites were identified and their
      profiles compared between groups using principal component analysis (PCA) and a
      mixed-effect two-way ANOVA model. Results. Animals recovered from surgery
      uneventfully. Analyses identified a metabolite profile that significantly differs
      in experimental conditions after controlling the False Discovery Rate (FDR). 16
      metabolites concentrations differed significantly when comparing samples from
      (LT+/LT-) to samples from (LG+/LG-) livers. A significant difference was also
      shown in 20 metabolites when comparing samples from (LT+) liver lobes to samples
      from (LT-) liver lobes. Conclusion. Normal liver tissue harboring malignancy had
      a distinct metabolic signature. The role of metabolic profiles on liver biopsies
      for the detection of early liver cancer remains to be determined. 

PMID- 24723741
TI  - Prognostic factors for long-term survival in patients with ampullary carcinoma:
      the results of a 15-year observation period after pancreaticoduodenectomy.
AB  - Introduction. Although ampullary carcinoma has the best prognosis among all
      periampullary carcinomas, its long-term survival remains low. Prognostic factors
      are only available for a period of 10 years after pancreaticoduodenectomy. The
      aim of this retrospective study was to identify factors that influence the long
      term patient survival over a 15-year observation period. Methods. From 1992 to
      2007, 143 patients with ampullary carcinoma underwent pancreatic resection. 86
      patients underwent pylorus-preserving pancreaticoduodenectomy (60%) and 57
      patients underwent standard Kausch-Whipple pancreaticoduodenectomy (40%).
      Results. The overall 1-, 5-, 10-, and 15-year survival rates were 79%, 40%, 24%,
      and 10%, respectively. Within a mean observation period of 30 (0-205) months, 100
      (69%) patients died. Survival analysis showed that positive lymph node
      involvement (P = 0.001), lymphatic vessel invasion (P = 0.0001), intraoperative
      administration of packed red blood cells (P = 0.03), an elevated CA 19-9 (P =
      0.03), jaundice (P = 0.04), and an impaired patient condition (P = 0.01) are
      strong negative predictors for a reduced patient survival. Conclusions. Patients
      with ampullary carcinoma have distinctly better long-term survival than patients
      with pancreatic adenocarcinoma. Long-term survival depends strongly on lymphatic
      nodal and vessel involvement. Moreover, a preoperative elevated CA 19-9 proved to
      be a significant prognostic factor. Adjuvant therapy may be essential in patients
      with this risk constellation. 

PMID- 24723742
TI  - Light-Directed Migration of D. discoideum Slugs in Microfabricated Confinements.
AB  - This paper investigates the light-driven migration of the multi-cellular
      microorganism Dictyostelium discoideum as a potential bio-actuation mechanism in
      microsystems. As a platform for slug migration we use microscale confinements,
      which consist of intersecting microchannels fabricated from solidified agar-water
      solution. The agar surface provides necessary moisture to the slugs during the
      experiment while remaining sufficiently stiff to allow effective slug migration.
      The movements of the slugs in the microchannels are driven and guided by
      phototaxis via controlling light transmitted through optical fibers. The
      microchannels impose geometrical confinements on the migrating slugs, improving
      the spatial precision of the migration. We demonstrate that slugs that form in a
      microchamber can be driven to migrate through the microchannels, as well as
      steered to a particular direction at microchannel intersections. Our experimental
      results indicate that slug movements can be more effectively controlled in
      microchannels, and potentially useful for bio-actuation applications.

PMID- 24723743
TI  - Microcantilever-Based Label-Free Characterization of Temperature-Dependent
      Biomolecular Affinity Binding.
AB  - This paper presents label-free characterization of temperature-dependent
      biomolecular affinity binding on solid surfaces using a microcantilever-based
      device. The device consists of a Parylene cantilever one side of which is coated
      with a gold film and functionalized with molecules as an affinity receptor to a
      target analyte. The cantilever is located in a poly(dimethylsiloxane) (PDMS)
      microfluidic chamber that is integrated with a transparent indium tin oxide (ITO)
      resistive temperature sensor on the underlying substrate. The ITO sensor allows
      for real-time measurements of the chamber temperature, as well as unobstructed
      optical access for reflection-based optical detection of the cantilever
      deflection. To test the temperature-dependent binding between the target and
      receptor, the temperature of the chamber is maintained at a constant setpoint,
      while a solution of unlabeled analyte molecules is continuously infused through
      the chamber. The measured cantilever deflection is used to determine the target
      receptor binding characteristics. We demonstrate label-free characterization of
      temperature-dependent binding kinetics of the platelet-derived growth factor
      (PDGF) protein with an aptamer receptor. Affinity binding properties including
      the association and dissociation rate constants as well as equilibrium
      dissociation constant are obtained, and shown to exhibit significant dependencies
      on temperature.

PMID- 24723744
TI  - 5-lipoxygenase-dependent recruitment of neutrophils and macrophages by eotaxin
      stimulated murine eosinophils.
AB  - The roles of eosinophils in antimicrobial defense remain incompletely understood.
      In ovalbumin-sensitized mice, eosinophils are selectively recruited to the
      peritoneal cavity by antigen, eotaxin, or leukotriene(LT)B4, a 5-lipoxygenase (5
      LO) metabolite. 5-LO blockade prevents responses to both antigen and eotaxin. We
      examined responses to eotaxin in the absence of sensitization and their
      dependence on 5-LO. BALB/c or PAS mice and their mutants (5-LO-deficient ALOX;
      eosinophil-deficient GATA-1) were injected i.p. with eotaxin, eosinophils, or
      both, and leukocyte accumulation was quantified up to 24 h. Significant
      recruitment of eosinophils by eotaxin in BALB/c, up to 24 h, was accompanied by
      much larger numbers of recruited neutrophils and monocytes/macrophages. These
      effects were abolished by eotaxin neutralization and 5-LO-activating protein
      inhibitor MK886. In ALOX (but not PAS) mice, eotaxin recruitment was abolished
      for eosinophils and halved for neutrophils. In GATA-1 mutants, eotaxin recruited
      neither neutrophils nor macrophages. Transfer of eosinophils cultured from bone
      marrow of BALB/c donors, or from ALOX donors, into GATA-1 mutant recipients,
      i.p., restored eotaxin recruitment of neutrophils and showed that the critical
      step dependent on 5-LO is the initial recruitment of eosinophils by eotaxin, not
      the secondary neutrophil accumulation. Eosinophil-dependent recruitment of
      neutrophils in naive BALB/c mice was associated with increased binding of
      bacteria. 

PMID- 24723746
TI  - What Adolescents Need to Prevent Relapse after Treatment for Substance Abuse: A
      Comparison of Youth, Parent, and Staff Perspectives.
AB  - OBJECTIVE: Little is known about what factors and supports youths identify as
      important for their sustained recovery after substance abuse treatment, and if
      their caregivers and treatment staff identify similar needs. The purpose of this
      study was to explore what youths, caregivers, and staff perceive as important to
      remain substance free after completing a residential treatment program. METHODS:
      Semi-structured interviews were conducted with 28 adolescents, 30 parents, and 29
      staff at 3 treatment agencies. Data were coded thematically and themes were
      organized by respondent type. RESULTS: There was high frequency and concordance
      across respondents regarding the need for aftercare services, supportive
      relationships, and activities. Only one item, outpatient treatment, demonstrated
      significant differences across groups. CONCLUSIONS: External supports and
      activities are important to recovery of adolescents from substances following
      treatment completion. Implications and potential areas of inquiry are discussed.

PMID- 24723745
TI  - Postnatal cytomegalovirus exposure in infants of antiretroviral-treated and
      untreated HIV-infected mothers.
AB  - HIV-1 and CMV are important pathogens transmitted via breastfeeding. Furthermore,
      perinatal CMV transmission may impact growth and disease progression in HIV
      exposed infants. Although maternal antiretroviral therapy reduces milk HIV-1 RNA
      load and postnatal transmission, its impact on milk CMV load is unclear. We
      examined the relationship between milk CMV and HIV-1 load (4-6 weeks postpartum)
      and the impact of antiretroviral treatment in 69 HIV-infected, lactating Malawian
      women and assessed the relationship between milk CMV load and postnatal growth in
      HIV-exposed, breastfed infants through six months of age. Despite an association
      between milk HIV-1 RNA and CMV DNA load (0.39 log(10) rise CMV load per log(10)
      rise HIV-1 RNA load, 95% CI 0.13-0.66), milk CMV load was similar in
      antiretroviral-treated and untreated women. Higher milk CMV load was associated
      with lower length-for-age (-0.53, 95% CI: -0.96, -0.10) and weight-for-age (
      0.40, 95% CI: -0.67, -0.13) Z-score at six months in exposed, uninfected infants.
      As the impact of maternal antiretroviral therapy on the magnitude of postnatal
      CMV exposure may be limited, our findings of an inverse relationship between
      infant growth and milk CMV load highlight the importance of defining the role of
      perinatal CMV exposure on growth faltering of HIV-exposed infants.

PMID- 24723747
TI  - Evaluation of Pharyngeal Function between No Bolus and Bolus Propofol Induced
      Sedation for Advanced Upper Endoscopy.
AB  - This study aimed to assess pharyngeal function between no bolus and bolus
      propofol induced sedation during gastric endoscopic submucosal dissection. A
      retrospective study was conducted involving consecutive gastric cancer patients.
      Patients in the no bolus group received a 3 mg/kg/h maintenance dose of propofol
      after the initiation of sedation without bolus injection. All patients in the
      bolus group received the same maintenance dose of propofol with bolus 0.5 mg/kg
      propofol injection. Pharyngeal functions were evaluated endoscopically for the
      first 5 min following the initial administration of propofol. Fourteen patients
      received no bolus propofol induction and 13 received bolus propofol induction.
      Motionless vocal cords were observed in 2 patients (14%) in the no bolus group
      and 3 (23%) in the bolus group. Trachea cartilage was not observed in the no
      bolus group but was apparent in 6 patients (46%) in the bolus group (P < 0.01).
      Scope stimulated pharyngeal reflex was observed in 11 patients (79%) in the no
      bolus group and in 3 (23%) in the bolus group (P < 0.01). Propofol induced
      sedation without bolus administration preserves pharyngeal function and may
      constitute a safer sedation method than with bolus. 

PMID- 24723748
TI  - Three new species of the millipede genus Hyleoglomeris Verhoeff, 1910 from the
      Aegean region of Greece (Diplopoda, Glomerida, Glomeridae).
AB  - Three new cavernicolous species of Hyleoglomeris are described from Greece:
      Hyleoglomerissubreducta sp.n., from Chios Island, Hyleoglomeristranslucida sp.n.,
      from Rhodes Island, and Hyleoglomerisinsularis sp.n., from Kalymnos Island, all
      in the Aegean Sea. 

PMID- 24723749
TI  - Emesopsisinfenestra Tatarnic, Wall & Cassis, 2011 (Heteroptera: Reduviidae),
      genus and species new to New Zealand.
AB  - Emesopsisinfenestra Tatarnic, Wall & Cassis, 2011 (Heteroptera: Reduviidae) is
      reported from New Zealand for the first time, based on a single specimen
      collected alive in the wild in Auckland in June 2013. The species was previously
      known only from Australia (Queensland) and the Loyalty Islands (New Caledonia). 

PMID- 24723750
TI  - New species of Lathrolestes Forster (Hymenoptera: Ichneumonidae) from Cote
      d'Ivoire.
AB  - Lathrolestesivoriensis sp. n. is described from Cote d'Ivoire. This is the second
      record of the genus from the Afrotropical region and the first record of the
      genus and the subfamily for the country. Illustrated re-description of
      Lathrolestesruwenzoricus (Benoit, 1955) is also provided. 

PMID- 24723751
TI  - A review of the subfamily Acaenitinae Forster, 1869 (Hymenoptera, Ichneumonidae)
      from Ukrainian Carpathians.
AB  - Ichneumonid wasps of the subfamily Acaenitinae Forster, 1869 are reviewed for the
      first time from the Ukrainian Carpathians. Two species, Coleocentrusexareolatus
      Kriechbaumer, 1894 and Coleocentrusheteropus Thomson, 1894 are new records for
      Ukraine. Arotesannulicornis Kriechbaumer, 1894 is considered to be a junior
      synonym of Arotesalbicinctus Gravenhorst, 1829 (syn. nov.). A key to species of
      Coleocentrus of the Carpathians is provided. 

PMID- 24723753
TI  - New records for Albania based on taxa from the Prespa National Park.
AB  - Twelve taxa are enumerated as new and three taxa confirmed for the flora of
      Albania. They were collected between 2007 and 2012 in the Prespa National Park of
      Albania which is part of the Prespa International Park, a biological protected
      area at the borders with F.Y.R. Macedonia and Greece. Four taxa, viz.,
      Centaureagalicicae, Festucagalicicae, Laserpitiumochridanum and
      Micromeriacristatasubsp.kosaninii are restricted to Dry and Galicica Mountains.
      Centaureadecora, a recently described species, is treated as a synonym of
      Centaureasoskae thus extending the known localities of the latter to the
      southeast. Detailed information on distribution, occurrence and habitats in
      Albania are provided for each taxon. 

PMID- 24723752
TI  - Eupolybothrus cavernicolus Komericki & Stoev sp. n. (Chilopoda: Lithobiomorpha:
      Lithobiidae): the first eukaryotic species description combining transcriptomic,
      DNA barcoding and micro-CT imaging data.
AB  - We demonstrate how a classical taxonomic description of a new species can be
      enhanced by applying new generation molecular methods, and novel computing and
      imaging technologies. A cave-dwelling centipede, Eupolybothrus cavernicolus
      Komericki & Stoev sp. n. (Chilopoda: Lithobiomorpha: Lithobiidae), found in a
      remote karst region in Knin, Croatia, is the first eukaryotic species for which,
      in addition to the traditional morphological description, we provide a fully
      sequenced transcriptome, a DNA barcode, detailed anatomical X-ray microtomography
      (micro-CT) scans, and a movie of the living specimen to document important traits
      of its ex-situ behaviour. By employing micro-CT scanning in a new species for the
      first time, we create a high-resolution morphological and anatomical dataset that
      allows virtual reconstructions of the specimen and subsequent interactive
      manipulation to test the recently introduced 'cybertype' notion. In addition, the
      transcriptome was recorded with a total of 67,785 scaffolds, having an average
      length of 812 bp and N50 of 1,448 bp (see GigaDB). Subsequent annotation of
      22,866 scaffolds was conducted by tracing homologs against current available
      databases, including Nr, SwissProt and COG. This pilot project illustrates a
      workflow of producing, storing, publishing and disseminating large data sets
      associated with a description of a new taxon. All data have been deposited in
      publicly accessible repositories, such as GigaScience GigaDB, NCBI, BOLD,
      Morphbank and Morphosource, and the respective open licenses used ensure their
      accessibility and re-usability.

PMID- 24723754
TI  - New country records of reptiles from Laos.
AB  - FOUR SPECIES OF REPTILES, OF WHICH ONE IS REPRESENTED BY ONE OF ITS SUBSPECIES,
      ARE RECORDED FOR THE FIRST TIME FROM LAOS: Cyrtodactylusphongnhakebangensis,
      Lycodonfutsingensis, and Lycodonruhstrati, as Lycodonruhstratiabditus, from
      limestone forests in Khammouane Province and Cyrtodactyluspseudoquadrivirgatus
      from hill evergreen forest in Salavan Province. These discoveries of lizards and
      snakes bring the total species number of reptiles to 189 in Laos. 

PMID- 24723755
TI  - Little known Orphninae (Coleoptera, Scarabaeidae) collected by the Madagascan
      expeditions of the California Academy of Sciences.
AB  - New locality records for Madecorphnusniger Frolov, 2010, Madecorphnusfalcatus
      Paulian, 1992, Madecorphnussimplex Frolov, 2010, and Triodontusitremoi Paulian,
      1977, are given. Endophallus armature of Madecorphnusniger Frolov, 2010, is
      described and illustrated. 

PMID- 24723756
TI  - Hesperinusninae Papp & Krivosheina (Diptera: Hesperinidae) from Georgia: the
      second record of this peculiar species.
AB  - A second record of Hesperinusninae Papp & Krivosheina, 2010 is given on the basis
      of material collected by sweep net from the northern slope of the Saguramo range
      north of Tbilisi, Georgia. The habitus and male terminalia are illustrated and
      the systematics briefly discussed. 

PMID- 24723757
TI  - Casuarinicolaaustralis Taylor, 2010 (Hemiptera: Triozidae), newly recorded from
      New Zealand.
AB  - The presence in New Zealand of the triozid Casuarinicolaaustralis Taylor, 2010 is
      reported for the first time, based on new material from Auckland. This is also
      the first record of the genus from New Zealand. 

PMID- 24723758
TI  - A record of Anzyginabilli Fletcher & Lariviere, 2009 (Hemiptera: Cicadellidae)
      from New Zealand.
AB  - The presence in New Zealand of the typhlocybine cicadellid Anzyginabilli Fletcher
      & Lariviere, 2009 is confirmed, based on new material from Auckland. Rubus sp. is
      confirmed as a host plant. 

PMID- 24723759
TI  - The millipede family Paradoxosomatidae in the Philippines, with a description of
      Eustrongylosomapenevi sp.n., and notes on Anoplodesmusanthracinus Pocock, 1895,
      recorded in Malaysia and Sri Lanka for the first time (Diplopoda, Polydesmida).
AB  - The Philippine fauna of the family Paradoxosomatidae is reviewed and shown to
      comprise only 12 certain species (+ one dubious), definitely only a fraction of
      the real diversity to be expected from such a large tropical archipelago. Two new
      combinations are proposed: Euphyodesmusphilippina (Nguyen Duc & Sierwald, 2010),
      comb. n. ex Desmoxytes Chamberlin, 1923, and Luzonomorphapolilloensis (San Juan &
      Lit, 2010), comb. n. ex Prionopeltis Pocock, 1895. The first representative of
      the large, basically Papuan genus Eustrongylosoma Silvestri, 1896 is described
      from Luzon, Philippines: Eustrongylosomapenevi sp. n. It differs from the other
      congeners in certain details of gonopod structure, as well as by the particularly
      long legs. Based on a restudy of the types of Strongylosomaluzoniense Peters,
      1864, from Luzon, the species is shown to be a new senior subjective synonym of
      Helicorthomorphaorthogona (Silvestri, 1898), syn. n. This formally results also
      in Helicorthomorphaluzoniensis (Peters, 1864), comb. n. Anoplodesmusanthracinus
      Pocock, 1895 is illustrated and briefly redescribed, based on material from State
      Pulau Penang, Malaysia, which represents the first formal record of the species
      in that country. This species is also new to the fauna of Sri Lanka. A review of
      the Anoplodesmus species reported from Sri Lanka, nearly all of them dubious, is
      presented. 

PMID- 24723760
TI  - Scutellistacaerulea (Fonscolombe, 1832) (Hymenoptera: Pteromalidae), new to New
      Zealand for the second time!
AB  - In 1921, Scutellistacaerulea was imported and released in Nelson, New Zealand,
      for the biological control of pest scale insects. It was thought to have failed
      to establish, and is therefore currently considered to be absent from the New
      Zealand fauna. On 17 April 2013, a live specimen was captured in the wild in
      Auckland. 

PMID- 24723761
TI  - MidMedPol: Polychaetes from midlittoral rocky shores in Greece and Italy
      (Mediterranean Sea).
AB  - This paper describes a dataset of polychaetes (Annelida) from 14 midlittoral
      rocky shore sampling sites in Greece and Italy (Mediterranean Sea). The dataset
      combines the outcome of four different projects studying the hard substrate
      midlittoral zone in the Mediterranean between 1984 and 2009. Samples were
      collected by scraping and collecting the organisms from a framed area. The
      maximal sampling depth was 1.5 m. In total, 123 polychaete species were recorded,
      five of which are new records for the respective biogeographic sectors of the
      Mediterranean. The dataset contains 788 occurrence records, fully annotated with
      all required metadata. These data contribute to the knowledge of a previously
      very understudied regional habitat, since at present, comprehensive lists of the
      midlittoral communities in the Mediterranean are provided through only a few,
      paper-based, studies. This dataset is one of the first electronic data
      compilations of the Mediterranean midlittoral zone communities and certainly the
      most comprehensive of its kind, contributing to the ongoing efforts of the Ocean
      Biogeographic Information System (OBIS) which aims at filling the gaps in our
      current knowledge of the world's oceans. It is accessible at
      http://ipt.vliz.be/resource.do?r=mediterraneanpolychaetaintertidal. 

PMID- 24723762
TI  - A new species of Lygistorrhina Skuse (Diptera: Sciaroidea: Lygistorrhinidae) from
      South Africa.
AB  - A new species of Lygistorrhina (Diptera, Sciaroidea, Lygistorrhinidae) from South
      Africa is described and a key for Afrotropical species of the genus is provided. 

PMID- 24723763
TI  - A new species of Tychobythinus Ganglbauer, 1896 (Coleoptera: Staphylinidae:
      Pselaphinae) from Turkey.
AB  - A new species of the genus Tychobythinus Ganglbauer, 1896, Tychobythinusoculatus
      sp. n., is described from near Koycegiz, Mugla Province, in southwestern Turkey.
      The new species is morphologically closely related to Tychobythinusabnormipes
      Reitter, 1910, and Tychobythinuspauper Kiesenwetter, 1858, but can be readily
      distinguished from both by having very simplified internal armature of the
      aedeagus, and by the specific shape of the gular depression. 

PMID- 24723764
TI  - The BioCASe Monitor Service - A tool for monitoring progress and quality of data
      provision through distributed data networks.
AB  - The BioCASe Monitor Service (BMS) is a web-based tool for coordinators of
      distributed data networks that provide information to web-portals and data
      aggregators via the BioCASe Provider Software. Building on common standards and
      protocols, it has three main purposes: (1) monitoring provider's progress in data
      provision, (2) facilitating checks of data mappings with a focus on the
      structure, plausibility and completeness, and (3) verifying compliance of
      provided data for transformation into other target schemas. Herein two use cases,
      GBIF-D and OpenUp!, are presented in which the BMS is being applied for
      monitoring the progress in data provision and performing quality checks on the
      ABCD (Access to Biological Collection Data) schema mapping. However, the BMS can
      potentially be used with any conceptual data schema and protocols for querying
      web services. Through flexible configuration options it is highly adaptable to
      specific requirements and needs. Thus, the BMS can be easily implemented into
      coordination workflows and reporting duties within other distributed data network
      projects. 

PMID- 24723765
TI  - New records of Paraleptophlebiawerneri Ulmer, 1920 and Paraleptophlebiastrandii
      (Eaton, 1901) from Finland (Ephemeroptera, Leptophlebiidae).
AB  - The mayfly species Paraleptophlebiawerneri has been rediscovered from Finland.
      The species was classified as RE (regionally extinct) in the most recent national
      red-list assessment. The new locality is close to the Russian border in NE
      Lapland, Savukoski. Adult males were collected with a sweep net around a pond.
      Paraleptophlebiastrandii is a rather poorly known but widespread Finnish species.
      The adults of this species occurred in great numbers in aapamires of central
      Lapland (Sodankyla). We hypothesize that these leptophlebid species are not
      dependent on running water but may instead thrive in small lentic water bodies. 

PMID- 24723766
TI  - Potential indicator species of climate changes occurring in Quebec, Part 1: the
      small brown lacewing fly Micromusposticus (Walker) (Neuroptera: Hemerobiidae).
AB  - Micromusposticus (Walker) is a small brown lacewing fly rarely collected in
      Canada and represented in collections by only a limited number of specimens.
      Indeed, fewer than 50 specimens were captured in Quebec and Ontario over the last
      century, all within a small area delimited by the northern shore of Lake Erie,
      Ottawa and Montreal. Aylmer, located on the north shore of the Ottawa River,
      northwest of Ottawa, is a new, most southwestern locality record of this species
      for Quebec. The Aylmer specimens were collected 1-7 days later than any of the
      known specimens collected elsewhere in Quebec or in Ontario, and 16-22 days later
      than in the neighbouring localities, indicating an apparent phenological shift. 

PMID- 24723767
TI  - Ground beetles (Coleoptera: Carabidae) of rice field banks and restored habitats
      in an agricultural area of the Po Plain (Lombardy, Italy).
AB  - An entomological investigation was carried out in an agricultural area, mainly
      rice fields, of the Po river plain, located in the municipalities of Lacchiarella
      (MI) and Giussago (PV) (Lombardy, Italy). In 2009 and 2010, ground beetles
      (Coleoptera: Carabidae) were sampled along rice field banks and in restored
      habitats, by means of pitfall traps. The area appeared as species-rich, compared
      to other anthropogenic habitats in the Po river pain. Most of the collected
      Carabids were species with a wide distribution in the Paleartic region, eurytopic
      and common in European agroecosystems. The assemblages were dominated by small
      medium, macropterous species, with summer larvae. No endemic species were found.
      Species with southern distribution, rarely found north of the Po river, were also
      sampled. Amaralittorea is recorded for the first time in Italy. 

PMID- 24723768
TI  - EXIF Custom: Automatic image metadata extraction for Scratchpads and Drupal.
AB  - Many institutions and individuals use embedded metadata to aid in the management
      of their image collections. Many deskop image management solutions such as Adobe
      Bridge and online tools such as Flickr also make use of embedded metadata to
      describe, categorise and license images. Until now Scratchpads (a data management
      system and virtual research environment for biodiversity) have not made use of
      these metadata, and users have had to manually re-enter this information if they
      have wanted to display it on their Scratchpad site. The Drupal described here
      allows users to map metadata embedded in their images to the associated field in
      the Scratchpads image form using one or more customised mappings. The module
      works seamlessly with the bulk image uploader used on Scratchpads and it is
      therefore possible to upload hundreds of images easily with automatic metadata
      (EXIF, XMP and IPTC) extraction and mapping. 

PMID- 24723769
TI  - Morphological variation in Echinorhynchustruttae Schrank, 1788 and the
      Echinorhynchusbothniensis Zdzitowiecki & Valtonen, 1987 species complex from
      freshwater fishes of northern Europe.
AB  - Echinorhynchustruttae and the Echinorhynchusbothniensis species complex are
      common parasites of salmoniform and other fishes in northern Europe.
      Echinorhynchusbothniensis and its sibling species Echinorhynchus 'bothniensis'
      are thought to be closely related to the Nearctic Echinorhynchusleidyi Van
      Cleave, 1924 based on morphological similarity and common usage of a mysid
      intermediate host. This study provides the first analysis of morphological and
      meristic variation in Echinorhynchustruttae and expands our knowledge of
      anatomical variability in the Echinorhynchusbothniensis group. Morphological
      variability in Echinorhynchustruttae was found to be far greater than previously
      reported, with part of the variance attributable to sexual dimorphism.
      Echinorhynchustruttae, the two species of the Echinorhynchusbothniensis group and
      Echinorhynchusleidyi displayed considerable interspecific overlap in the ranges
      of all conventional morphological characters. However, Proboscis profiler, a tool
      for detecting acanthocephalan morphotypes using multivariate analysis of hook
      morphometrics, successfully separated Echinorhynchustruttae from the other taxa.
      The Echinorhynchusbothniensis species group could not be reliably distinguished
      from Echinorhynchusleidyi (or each other), providing further evidence of the
      affinity of these taxa. Observations on the distribution of Echinorhynchustruttae
      in its definitive host population are also reported. 

PMID- 24723770
TI  - A second update to the checklist of Finnish long-legged flies (Diptera:
      Dolichopodidae), with a re-evaluation of the status of Hydrophoruscallosoma Frey,
      1915.
AB  - Eighteen species of long-legged flies (Dolichopodidae) are reported as new to
      Finland. A further species, Microphorellapraecox (Loew), is confirmed as a
      Finnish species. The status of Hydrophoruscallosoma Frey, 1915 is re-evaluated
      and a lectotype is designated for the species. Hydrophorusalbosignatus Ringdahl,
      1919 is found to be a junior synonym of Hydrophoruscallosoma (syn. n.).
      Characters for identifying both sexes of Hydrophoruscallosoma and
      Hydrophorusaltivagus Aldrich are presented and illustrated with high-quality
      photographs. 

PMID- 24723771
TI  - Faunistic diversity of spiders (Araneae) in Galichitsa mountain (FYR Macedonia).
AB  - A total of 294 species from 31 families have been found in Galichitsa Mt. Of
      them, 85 species are new to the mountain, while 20 are also new to the fauna of
      FYR of Macedonia. According to their current distribution the established species
      can be assigned to 17 zoogeographical categories, grouped into 5 complexes
      (Cosmopolitan, Holarctic, European, Mediterranean, Endemics of Balkans). Dominant
      are Holarctic species (66.0%) followed by European (16.5%) and Mediterranean
      (9.3%). The endemics (6.2%) and Southeast European species (1.7%) emphasize the
      local character of this fauna, but its low percentage suggests an important
      process of colonization. 

PMID- 24723772
TI  - First record of Tettigettalnamariae Quartau & Boulard, 1995 (Insecta: Hemiptera:
      Cicadoidea) in Spain.
AB  - Tettigettalnamariae Quartau & Boulard 1995 is recorded for the first time in
      Spain. Thought to be endemic to Portugal (occurring in the southern province of
      Algarve), the present paper adds its distribution to southern Spain, being an
      Iberian endemism. The acoustic signals of the new specimens collected were
      recorded in different localities of Huelva province, in Andalusia during August
      2012. According to their present known distribution, specimens of
      Tettigettalnamariae tend to be sparsely distributed in small range populations in
      southern Iberian Peninsula, favouring wooded areas with Pinuspinea. 

PMID- 24723773
TI  - A contribution to the study of the Lower Volga center of scarab beetle diversity
      in Russia: checklist of the tribe Aphodiini (Coleoptera, Scarabaeidae) of Dosang
      environs.
AB  - The field sampling of the Aphodiini scarab beetles in Dosang environs (Astrakhan
      Province, European Russia) in 2006-2012 resulted in the collection of 44 species.
      All but one of them belong to Aphodius Hellwig (sensu lato). This is apparently
      the richest recorded local Aphodiini fauna in Russia. The high Aphodiini
      diversity in the area can be explained by the long vegetative season with high
      effective heat sum, large livestock providing abundant food resources throughout
      the year, and location in the transition belt between Volga-Akhtuba Floodplain
      and Desert floristic districts. The core fauna consists of mesophilous species
      widely distributed in the Palearctic region and confined to the intrazonal
      habitats. Other species have ranges mostly limited to the steppe, semidesert, and
      desert zones. 

PMID- 24723774
TI  - Targeting a portion of central European spider diversity for permanent
      preservation.
AB  - Given the limited success of past and current conservation efforts, an
      alternative approach is to preserve tissues and genomes of targeted organisms in
      cryobanks to make them accessible for future generations. Our pilot preservation
      project aimed to obtain, expertly identify, and permanently preserve a quarter of
      the known spider species diversity shared between Slovenia and Switzerland,
      estimated at 275 species. We here report on the faunistic part of this project,
      which resulted in 324 species (227 in Slovenia, 143 in Switzerland) for which
      identification was reasonably established. This material is now preserved in
      cryobanks, is being processed for DNA barcoding, and is available for genomic
      studies. 

PMID- 24723775
TI  - The millipede Typhloglomeriscaucasica Golovatch, 1975 found epigeically
      (Diplopoda, Glomerida, Glomeridellidae).
AB  - The millipede Typhloglomeriscaucasica Golovatch, hitherto considered as a
      troglobite confined to several caves near Sochi, western Caucasus, Russia, is
      recorded epigeically in the same region, and is therefore a troglophile. 

PMID- 24723776
TI  - First record of the male of the widespread Calliscelioelegans (Perkins)
      (Hymenoptera, Platygastridae) along with some taxonomic notes on the species.
AB  - The hitherto unknown male of the widespread and tramp species, Calliscelioelegans
      (Hymenoptera, Platygastridae) is hereby reported for the first time, from India.
      The two sexes are chromatically quite similar. The male has the same conspicuous
      banding pattern in the forewing as that of the female. The status of
      Caloteleatanugatra Narendran (Hymenoptera, Platygastridae) from India is reviewed
      and is proposed to be a junior synonym of Calliscelioelegans, new synonymy.
      Distribution of Calliscelioelegans in India is mapped. 

PMID- 24723777
TI  - A visual identification key utilizing both gestalt and analytic approaches to
      identification of Carices present in North America (Plantae, Cyperaceae).
AB  - Images are a critical part of the identification process because they enable
      direct, immediate and relatively unmediated comparisons between a specimen being
      identified and one or more reference specimens. The Carices Interactive Visual
      Identification Key (CIVIK) is a novel tool for identification of North American
      Carex species, the largest vascular plant genus in North America, and two less
      numerous closely-related genera, Cymophyllus and Kobresia. CIVIK incorporates
      1288 high-resolution tiled image sets that allow users to zoom in to view minute
      structures that are crucial at times for identification in these genera.
      Morphological data are derived from the earlier Carex Interactive Identification
      Key (CIIK) which in turn used data from the Flora of North America treatments. In
      this new iteration, images can be viewed in a grid or histogram format, allowing
      multiple representations of data. In both formats the images are fully zoomable. 

PMID- 24723778
TI  - From Corsica to Britain: new outdoor records of Ocnerodrilidae (Annelida:
      Clitellata) in western Europe.
AB  - The ocnerodrilids Eukerriasaltensis (Beddard, 1895) and Ocnerodrilusoccidentalis
      Eisen, 1878 are reported for the first time from outdoor localities above 42
      degrees  N in Europe. The present new records comprise the first ever from
      England (River Thames, central London) and from France (River Golo, northern
      Corsica) and the northernmost occurrences in Italy (Liguria and Veneto). The new
      latitudinal limits and the numerosity of outdoor records suggest that the current
      environmental and climate changes are substantially enhancing the dispersal and
      survival possibilities of these worms, even though different transport vectors
      seem to be involved for the two species. 

PMID- 24723779
TI  - Chinese species of egg-parasitoids of the genera Oxyscelio Kieffer, Heptascelio
      Kieffer and Platyscelio Kieffer (Hymenoptera: Platygastridaes.l., Scelioninae).
AB  - To date, the known Chinese fauna of egg-parasitoids of the genus Oxyscelio
      Kieffer encompasses two species from the mainland - Oxysceliodoumao Burks and
      Oxyscelionubbin Burks. Here we record eighteen species of Oxyscelio from
      collections in mainland China: Oxyscelioarvi Burks, Oxyscelioceylonensis (Dodd),
      Oxyscelioconvergens Burks, Oxysceliocordis Burks, Oxysceliocrebritas Burks,
      Oxysceliocuculli Burks, Oxysceliodermatoglyphes Burks, Oxysceliodoumao Burks,
      Oxyscelioflorus Kononova, Oxysceliogranorum Burks, Oxysceliointermedietas Burks,
      Oxysceliojugi Burks, Oxysceliokramatos Burks, Oxysceliolongiventris Burks,
      Oxyscelionaraws Kozlov & Le, Oxyscelioperpensus Kononova, Oxyscelioplanocarinae
      Burks, and Oxysceliostriarum Burks. Oxyscelio is primarily found in the tropics,
      and most of these species are shared with Taiwan and southeast Asia. Three
      species previously known only from Japan, Oxyscelioarvi, Oxyscelioflorus,
      Oxyscelioperpensus, are shared. The Chinese species are recorded from Guangdong,
      Guangxi, Hainan, Hebei, Hunan, Shaanxi, Sichuan, Yunnan and Zhejiang as well as
      additional material from Taiwan. Heptasceliohamatus Masner & Johnson and
      Platysceliopulchricornis Kieffer are both recorded from Hainan and Guangdong, as
      well as records of Platysceliopulchricornis from Sarawak and Thailand. 

PMID- 24723780
TI  - Spider hosts (Arachnida, Araneae) and wasp parasitoids (Insecta, Hymenoptera,
      Ichneumonidae, Ephialtini) matched using DNA barcodes.
AB  - The study of parasitoids and their hosts suffers from a lack of reliable
      taxonomic data. We use a combination of morphological characters and DNA
      sequences to produce taxonomic determinations that can be verified with reference
      to specimens in an accessible collection and DNA barcode sequences posted to the
      Barcode of Life database (BOLD). We demonstrate that DNA can be successfully
      extracted from consumed host spiders and the shed pupal case of a wasp using non
      destructive methods. We found Acrodactylaquadrisculpta to be a parasitoid of
      Tetragnathamontana; Zatypotapercontatoria and Zatypotabohemani both are
      parasitoids of Neottiurabimaculata. Zatypotaanomala is a parasitoid of an as yet
      unidentified host in the family Dictynidae, but the host species may be possible
      to identify in the future as the library of reference sequences on BOLD continues
      to grow. The study of parasitoids and their hosts traditionally requires
      specialized knowledge and techniques, and accumulating data is a slow process.
      DNA barcoding could allow more professional and amateur naturalists to contribute
      data to this field of study. A publication venue dedicated to aggregating
      datasets of all sizes online is well suited to this model of distributed science.

PMID- 24723781
TI  - Xanthichthysgreenei, a new species of triggerfish (Balistidae) from the Line
      Islands.
AB  - Xanthichthysgreenei sp. n. is described from six specimens, 97-154 mm standard
      length (SL) collected from mesophotic coral ecosystems (90-100 m) at Kiritimati
      (Christmas Island), Line Islands, part of the Republic of Kiribati in the Central
      Pacific. Of the six species of Xanthichthys, it is most similar to the Atlantic
      Xanthichthysringens and the Indo-West Pacific Xanthichthyslineopunctatus, sharing
      with these species the character of three pigmented cheek grooves. It is
      distinctive in its low body scale row count (33-35, other Xanthichthys species
      with 39 or more), small size (maximum SL 154 mm, other species over 225 mm), and
      color pattern of scattered dark spots sub-dorsally and no other spots or lines on
      body. 

PMID- 24723782
TI  - Beyond dead trees: integrating the scientific process in the Biodiversity Data
      Journal.

PMID- 24723783
TI  - An updated checklist of aquatic plants of Myanmar and Thailand.
AB  - The flora of Tropical Asia is among the richest in the world, yet the actual
      diversity is estimated to be much higher than previously reported. Myanmar and
      Thailand are adjacent countries that together occupy more than the half the area
      of continental Tropical Asia. This geographic area is diverse ecologically,
      ranging from cool-temperate to tropical climates, and includes from coast,
      rainforests and high mountain elevations. An updated checklist of aquatic plants,
      which includes 78 species in 44 genera from 24 families, are presented based on
      floristic works. This number includes seven species, that have never been listed
      in the previous floras and checklists. The species (excluding non-indigenous
      taxa) were categorized by five geographic groups with the exception of to reflect
      the rich diversity of the countries' floras. 

PMID- 24723784
TI  - Sphodromantisviridis (Forskal, 1775): New for Portugal and new records of the
      rare and small mantids Apteromantisaptera (Fuente, 1894) and
      Perlamantisallibertii Guerin-Meneville, 1843 in the country (Mantodea: Mantidae
      and Amorphoscelidae).
AB  - Several new records are presented on some of the least known mantis species in
      the Iberian Peninsula. From data collected in Portugal, their analysis has proven
      to represent an important advancement in the knowledge of this group of insects
      for the country and the Western Mediterranean area. Twenty new citations provide
      a better understanding on the distribution of the crepuscular species
      Perlamantisallibertii, the IUCN red listed Apteromantisaptera and the first
      Portuguese records of Sphodromantisviridis, extending their western limits of
      occurrence in Europe. The data thus gathered emphasizes the need to invest in
      biodiversity assessment for increased knowledge on species distribution and
      phenology but also for monitoring over time, essential to better ascertaining
      ecosystem services, the effects of climate change and habitat conservation. 

PMID- 24723785
TI  - Linking multiple biodiversity informatics platforms with Darwin Core Archives.
AB  - We describe an implementation of the Darwin Core Archive (DwC-A) standard that
      allows for the exchange of biodiversity information contained within the
      Scratchpads virtual research environment with external collaborators. Using this
      single archive file Scratchpad users can expose taxonomies, specimen records,
      species descriptions and a range of other data to a variety of third-party
      aggregators and tools (currently Encyclopedia of Life, eMonocot Portal, CartoDB,
      and the Common Data Model) for secondary use. This paper describes our technical
      approach to dynamically building and validating Darwin Core Archives for the 600+
      Scratchpad user communities, which can be used to serve the diverse data needs of
      all of our content partners. 

PMID- 24723786
TI  - New records of Microgasterdeductor Nixon, 1968 (Hymenoptera: Braconidae:
      Microgastrinae) for the Holarctic region, with comments on its historical
      distribution.
AB  - Four new localities for the species Microgasterdeductor Nixon (1968) are recorded
      from the Nearctic (Canada and the United States) and the Palaearctic (Sweden),
      expanding significantly the range of the species. Microgasterdeductor seems to be
      widely distributed in boreal areas of the Holarctic, and it is characterized by
      unique morphological (tarsal claw structure) and molecular (COI) traits.
      Preliminary evidence, to be corroborated when more data is available, suggests
      that the species might have shifted northwards between 1950 and the present day. 

PMID- 24723787
TI  - First report of the genus Conostigmus Dahlbom (Hymenoptera: Ceraphronoidea:
      Megaspilidae) from India with description of a new species.
AB  - The genus Conostigmus Dahlbom (Hymenoptera: Ceraphronoidea: Megaspilidae) is
      reported for the first time from India, along with description and illustration
      of Conostigmusneotubifer sp. n. A comparative discussion on the morphological
      affinities of the new species with its putative sister Conostigmustubifer Dessart
      is provided. An intermixing of character states of genera Conostigmus as well as
      Dendrocerus Ratzeburg is observed. 

PMID- 24723788
TI  - Developing Race Categories in Infancy via Bayesian Face Recognition.
AB  - The other-race effect emerges during infancy following the perceptual narrowing
      of face recognition. Other-race faces that were previously discriminable in early
      infancy cannot be distinguished by older infants. Presently, I discuss a Bayesian
      model of this process that posits that the other-race effect may be a consequence
      of learning to distinguish between intra-personal variation (changes to face
      appearance that preserve identity) and extra-personal variation (changes that do
      not preserve identity) in a visual environment in which a subset of race
      categories dominate. I demonstrate that race categories, which I have previously
      argued are a critical pre-cursor to the emergence of the other-race effect in
      infancy, are a natural by-product of this model. Perceptual narrowing for race
      may thus be a natural consequence of visual experience and the estimation of face
      variability based on a growing number of exemplars. I describe the basic
      architecture of the model, its applicability to a range of visual learning
      scenarios, and identify critical choices one faces in applying the model to a
      specific perceptual task. Despite the success of the model in accounting for
      these behavioral results, I conclude by identifying important shortcomings of the
      model and describe important challenges for future efforts to characterize the
      development of the other-race effect computationally.

PMID- 24723789
TI  - Comorbidity in adult bone sarcoma patients: a population-based cohort study.
AB  - Background. Comorbidity is an important prognostic factor for survival in
      different cancers; however, neither the prevalence nor the impact of comorbidity
      has been investigated in bone sarcoma. Methods. All adult bone sarcoma patients
      from western Denmark treated at the Aarhus Sarcoma Centre in the period from 1979
      to 2008 were identified through a validated population-based database. Charlson
      Comorbidity Index scores were computed, using discharge diagnoses from the Danish
      National Patient Registry. Survival was assessed as overall and disease-specific
      mortality. The impact of comorbidity was examined as rates according to the level
      of comorbidity as well as uni- and multivariately using proportional hazard
      models. Results. A total of 453 patients were identified. The overall prevalence
      of comorbidity was 19%. The prevalence increased with age and over the study
      period. In patients with Ewing/osteosarcoma, comorbidity was not associated with
      an increased overall or disease-specific mortality. However, patients with bone
      sarcomas other than Ewing/osteosarcoma had increased overall mortality.
      Independent prognostic factors for disease-specific survival were age, tumor
      size, stage at diagnosis, soft tissue involvement, grade, and surgery.
      Conclusion. The prevalence of comorbidity in bone sarcoma patients is low.
      Comorbidity impaired survival in patients with non-Ewing/nonosteosarcoma,
      histology. This emphasizes the importance of not only treating the sarcoma but
      also comorbidity. 

PMID- 24723790
TI  - Enhancing knowledge sharing management using BIM technology in construction.
AB  - Construction knowledge can be communicated and reused among project managers and
      jobsite engineers to alleviate problems on a construction jobsite and reduce the
      time and cost of solving problems related to constructability. This paper
      proposes a new methodology for the sharing of construction knowledge by using
      Building Information Modeling (BIM) technology. The main characteristics of BIM
      include illustrating 3D CAD-based presentations and keeping information in a
      digital format and facilitation of easy updating and transfer of information in
      the BIM environment. Using the BIM technology, project managers and engineers can
      gain knowledge related to BIM and obtain feedback provided by jobsite engineers
      for future reference. This study addresses the application of knowledge sharing
      management using BIM technology and proposes a BIM-based Knowledge Sharing
      Management (BIMKSM) system for project managers and engineers. The BIMKSM system
      is then applied in a selected case study of a construction project in Taiwan to
      demonstrate the effectiveness of sharing knowledge in the BIM environment. The
      results demonstrate that the BIMKSM system can be used as a visual BIM-based
      knowledge sharing management platform by utilizing the BIM technology. 

PMID- 24723791
TI  - Parameter and state estimator for state space models.
AB  - This paper proposes a parameter and state estimator for canonical state space
      systems from measured input-output data. The key is to solve the system state
      from the state equation and to substitute it into the output equation,
      eliminating the state variables, and the resulting equation contains only the
      system inputs and outputs, and to derive a least squares parameter identification
      algorithm. Furthermore, the system states are computed from the estimated
      parameters and the input-output data. Convergence analysis using the martingale
      convergence theorem indicates that the parameter estimates converge to their true
      values. Finally, an illustrative example is provided to show that the proposed
      algorithm is effective. 

PMID- 24723792
TI  - Robust ear recognition via nonnegative sparse representation of Gabor orientation
      information.
AB  - Orientation information is critical to the accuracy of ear recognition systems.
      In this paper, a new feature extraction approach is investigated for ear
      recognition by using orientation information of Gabor wavelets. The proposed
      Gabor orientation feature can not only avoid too much redundancy in conventional
      Gabor feature but also tend to extract more precise orientation information of
      the ear shape contours. Then, Gabor orientation feature based nonnegative sparse
      representation classification (Gabor orientation + NSRC) is proposed for ear
      recognition. Compared with SRC in which the sparse coding coefficients can be
      negative, the nonnegativity of NSRC conforms to the intuitive notion of combining
      parts to form a whole and therefore is more consistent with the biological
      modeling of visual data. Additionally, the use of Gabor orientation features
      increases the discriminative power of NSRC. Extensive experimental results show
      that the proposed Gabor orientation feature based nonnegative sparse
      representation classification paradigm achieves much better recognition
      performance and is found to be more robust to challenging problems such as pose
      changes, illumination variations, and ear partial occlusion in real-world
      applications. 

PMID- 24723793
TI  - Study of query expansion techniques and their application in the biomedical
      information retrieval.
AB  - Information Retrieval focuses on finding documents whose content matches with a
      user query from a large document collection. As formulating well-designed queries
      is difficult for most users, it is necessary to use query expansion to retrieve
      relevant information. Query expansion techniques are widely applied for improving
      the efficiency of the textual information retrieval systems. These techniques
      help to overcome vocabulary mismatch issues by expanding the original query with
      additional relevant terms and reweighting the terms in the expanded query. In
      this paper, different text preprocessing and query expansion approaches are
      combined to improve the documents initially retrieved by a query in a scientific
      documental database. A corpus belonging to MEDLINE, called Cystic Fibrosis, is
      used as a knowledge source. Experimental results show that the proposed
      combinations of techniques greatly enhance the efficiency obtained by traditional
      queries. 

PMID- 24723794
TI  - Stego on FPGA: an IWT approach.
AB  - A reconfigurable hardware architecture for the implementation of integer wavelet
      transform (IWT) based adaptive random image steganography algorithm is proposed.
      The Haar-IWT was used to separate the subbands namely, LL, LH, HL, and HH, from 8
      * 8 pixel blocks and the encrypted secret data is hidden in the LH, HL, and HH
      blocks using Moore and Hilbert space filling curve (SFC) scan patterns. Either
      Moore or Hilbert SFC was chosen for hiding the encrypted data in LH, HL, and HH
      coefficients, whichever produces the lowest mean square error (MSE) and the
      highest peak signal-to-noise ratio (PSNR). The fixated random walk's verdict of
      all blocks is registered which is nothing but the furtive key. Our system took
      1.6 us for embedding the data in coefficient blocks and consumed 34% of the logic
      elements, 22% of the dedicated logic register, and 2% of the embedded multiplier
      on Cyclone II field programmable gate array (FPGA).

PMID- 24723795
TI  - Interactive reference point procedure based on the conic scalarizing function.
AB  - In multiobjective optimization methods, multiple conflicting objectives are
      typically converted into a single objective optimization problem with the help of
      scalarizing functions. The conic scalarizing function is a general
      characterization of Benson proper efficient solutions of non-convex
      multiobjective problems in terms of saddle points of scalar Lagrangian functions.
      This approach preserves convexity. The conic scalarizing function, as a part of a
      posteriori or a priori methods, has successfully been applied to several real
      life problems. In this paper, we propose a conic scalarizing function based
      interactive reference point procedure where the decision maker actively takes
      part in the solution process and directs the search according to her or his
      preferences. An algorithmic framework for the interactive solution of multiple
      objective optimization problems is presented and is utilized for solving some
      illustrative examples. 

PMID- 24723796
TI  - Free vibrations of a trapezoidal plate with an internal line hinge.
AB  - This paper deals with a general variational formulation for the determination of
      natural frequencies and mode shapes of free vibrations of laminated thin plates
      of trapezoidal shape with an internal line hinge restrained against rotation. The
      analysis was carried out by using the kinematics corresponding to the classical
      laminated plate theory (CLPT). The eigenvalue problem is obtained by employing a
      combination of the Ritz method and the Lagrange multipliers method. The domain of
      the plate is transformed into a rectangular domain in the computational space by
      using nonorthogonal triangular coordinates and the transverse displacements are
      approximated with a set of simple polynomials automatically generated and
      expressed in the triangular coordinates. The developed algorithm allows obtaining
      approximate analytical solutions for mentioned plate with different geometries,
      aspect ratio, position of the line hinge, and boundary conditions including
      translational and rotational elastically restrained edges. It allows studying the
      influence of the mentioned line on the vibration frequencies and respective mode
      shapes. The algorithm can easily be programmed and it is numerically stable.
      Additionally, as a particular case, the results of triangular plates can be
      easily generated. 

PMID- 24723797
TI  - Fall-related emergency department admission: fall environment and settings and
      related injury patterns in 6357 patients with special emphasis on the elderly.
AB  - PRINCIPALS: Throughout the world, falls are a major public health problem and a
      socioeconomic burden. Nevertheless there is little knowledge about how the injury
      types may be related to the aetiology and setting of the fall, especially in the
      elderly. We have therefore analysed all patients presenting with a fall to our
      Emergency Department (ED) over the past five years. METHODS: Our retrospective
      data analysis comprised adult patients admitted to our Emergency Department
      between January 1, 2006, and December 31, 2010, in relation to a fall. RESULTS:
      Of a total of 6357 patients 78% (n = 4957) patients were younger than 75 years.
      The main setting for falls was patients home (n = 2239, 35.3%). In contrast to
      the younger patients, the older population was predominantly female (56.3% versus
      38.6%; P < 0.0001). Older patients were more likely to fall at home and suffer
      from medical conditions (all P < 0.0001). Injuries to the head (P < 0.0001) and
      to the lower extremity (P < 0.019) occurred predominantly in the older
      population. Age was the sole predictor for recurrent falls (OR 1.2, P < 0.0001).
      CONCLUSION: Falls at home are the main class of falls for all age groups,
      particularly in the elderly. Fall prevention strategies must therefore target
      activities of daily living. Even though falls related to sports mostly take place
      in the younger cohort, a significant percentage of elderly patients present with
      falls related to sporting activity. Falls due to medical conditions were most
      likely to result in mild traumatic brain injury.

PMID- 24723798
TI  - Mineral phases and release behaviors of as in the process of sintering residues
      containing as at high temperature.
AB  - To investigate the effect of sintering temperature and sintering time on arsenic
      volatility and arsenic leaching in the sinter, we carried out experimental works
      and studied the structural changes of mineral phases and microstructure
      observation of the sinter at different sintering temperatures. Raw materials were
      shaped under the pressure of 10 MPa and sintered at 1000~1350 degrees C for 45
      min with air flow rate of 2000 mL/min. The results showed that different
      sintering temperatures and different sintering times had little impact on the
      volatilization of arsenic, and the arsenic fixed rate remained above 90%;
      however, both factors greatly influenced the leaching concentration of arsenic.
      Considering the product's environmental safety, the best sintering temperature
      was 1200 degrees C and the best sintering time was 45 min. When sintering
      temperature was lower than 1000 degrees C, FeAsS was oxidized into calcium,
      aluminum, and iron arsenide, mainly Ca3(AsO4)2 and AlAsO4, and the arsenic
      leaching was high. When it increased to 1200 degrees C, arsenic was surrounded by
      a glass matrix and became chemically bonded inside the matrix, which lead to
      significantly lower arsenic leaching.

PMID- 24723799
TI  - An efficient in vitro plantlet regeneration from shoot tip cultures of Curculigo
      latifolia, a medicinal plant.
AB  - A procedure was developed for in vitro propagation of Curculigo latifolia through
      shoot tip culture. Direct regeneration and indirect scalp induction of Curculigo
      latifolia were obtained from shoot tip grown on MS medium supplemented with
      different concentrations and combinations of thidiazuron and indole-3-butyric
      acid. Maximum response for direct regeneration in terms of percentage of explants
      producing shoot, shoot number, and shoot length was obtained on MS medium
      supplemented with combination of thidiazuron (0.5 mg L(-1)) and indole-3-butyric
      acid (0.25 mg L(-1)) after both 10 and 14 weeks of cultures. Indole-3-butyric
      acid in combination with thidiazuron exhibited a synergistic effect on shoot
      regeneration. The shoot tips were able to induce maximum scalp from basal end of
      explants on the medium with 2 mg L(-1) thidiazuron. Cultures showed that shoot
      number, shoot length, and scalp size increased significantly after 14 weeks of
      culture. Transferring of the shoots onto the MS medium devoid of growth
      regulators resulted in the highest percentage of root induction and longer roots,
      while medium supplemented with 0.25 mg L(-1) IBA produced more numbers of roots.

PMID- 24723800
TI  - Analytical properties of credibilistic expectation functions.
AB  - The expectation function of fuzzy variable is an important and widely used
      criterion in fuzzy optimization, and sound properties on the expectation function
      may help in model analysis and solution algorithm design for the fuzzy
      optimization problems. The present paper deals with some analytical properties of
      credibilistic expectation functions of fuzzy variables that lie in three aspects.
      First, some continuity theorems on the continuity and semicontinuity conditions
      are proved for the expectation functions. Second, a differentiation formula of
      the expectation function is derived which tells that, under certain conditions,
      the derivative of the fuzzy expectation function with respect to the parameter
      equals the expectation of the derivative of the fuzzy function with respect to
      the parameter. Finally, a law of large numbers for fuzzy variable sequences is
      obtained leveraging on the Chebyshev Inequality of fuzzy variables. Some examples
      are provided to verify the results obtained. 

PMID- 24723801
TI  - Genetic biodiversity of Italian olives (Olea europaea) germplasm analyzed by SSR
      markers.
AB  - The olive is an important fruit species cultivated for oil and table olives in
      Italy and the Mediterranean basin. The conservation of cultivated plants in ex
      situ collections is essential for the optimal management and use of their genetic
      resources. The largest ex situ olive germplasm collection consists of
      approximately 500 Italian olive varieties and corresponding to 85% of the total
      Italian olive germplasm is maintained at the Consiglio per la Ricerca e
      sperimentazione per l'Agricoltura, Centro di Ricerca per l'Olivicoltura e
      l'Industria Olearia (CRA-OLI), in Italy. In this work, eleven preselected nuclear
      microsatellite markers were used to assess genetic diversity, population
      structure, and gene flows with the aim of assembling a core collection. The
      dendrogram obtained utilizing the unweighted pair group method highlights the
      presence of homonymy and synonymy in olive tree datasets analyzed in this study.
      439 different unique genotype profiles were obtained with this combination of 11
      loci nSSR, representing 89.8% of the varieties analyzed. The remaining 10.2%
      comprises different variety pairs in which both accessions are genetically
      indistinguishable. Clustering analysis performed using BAPS software detected
      seven groups in Italian olive germplasm and gene flows were determined among
      identified clusters. We proposed an Italian core collection of 23 olive varieties
      capturing all detected alleles at microsatellites. The information collected in
      this study regarding the CRA-OLI ex situ collection can be used for breeding
      programs, for germplasm conservation, and for optimizing a strategy for the
      management of olive gene pools. 

PMID- 24723802
TI  - Effective design of profiling float network for oceanic heat-content monitoring.
AB  - Schemes for optimizing ocean observation programs are presently the subject of
      increased interest since in principle they should lead to the improved
      understanding of the dynamical state of the ocean that is required within the
      present regime of climate change. Here we use an adjoint sensitivity analysis
      together with a four-dimensional fluctuating oceanic current system to identify
      key regions for intensive monitoring by drifting profiling float. In this way we
      aim to maximize observational efficiency. As a scientific benchmark for the
      validity of our approach, we have attempted to define the ambient sensitivity of
      the oceanic heat content to a subtle change in water temperature within the
      Pacific Basin. We focus on the interannual to multidecadal variations in
      particular. As a result, sensitivity signals reflecting changes in heat content
      exhibit a characteristic pattern in the three-dimensional continuum and have
      drastic temporal changes. This implies that the key regions will depend greatly
      on the operational timeframe of the observing system. We demonstrate a more
      effective geographic deployment strategy for the profiling floats monitoring
      changes in the oceanic heat content on a decadal timescale. 

PMID- 24723803
TI  - Pedometers and aerobic capacity: evaluating an elementary after-school running
      program.
AB  - Childhood obesity affects 1 of every 6 youth in the United States. One
      contributing factor to this statistic is a lack of physical activity (PA).
      Demands related to accountability which are placed on educators to demonstrate
      academic achievement often result in resistance to allocating time during the
      school day for PA. One possible solution is to consider utilizing time after
      school to integrate PA programs. The purpose of this study was to assess the
      impact of a 12-week after-school pedometer-focused PA program on aerobic capacity
      and to examine the relationship between step count and aerobic capacity in
      elementary school aged children. A group of elementary students (n = 24; 9.5 +/-
      0.9 years) participated in a 12-week pedometer-focused PA program that included
      pretraining and posttraining fitness testing via the 20-meter version of the
      PACER test. Paired sample t-tests revealed significant differences between the
      pretest (M = 21.0 laps, SD = 9.9) and posttest (M = 25.2 laps, SD = 12.2) scores
      (t = 4.04, P <= 0.001). A Pearson correlation revealed no significant
      relationship between individual step count and the difference between PACER pre-
      and posttest (r = 0.318, P = 0.130). The program improved aerobic capacity, but
      an increase in pedometer-calculated step count was not a predictor. 

PMID- 24723804
TI  - Body fat percentage prediction using intelligent hybrid approaches.
AB  - Excess of body fat often leads to obesity. Obesity is typically associated with
      serious medical diseases, such as cancer, heart disease, and diabetes.
      Accordingly, knowing the body fat is an extremely important issue since it
      affects everyone's health. Although there are several ways to measure the body
      fat percentage (BFP), the accurate methods are often associated with hassle
      and/or high costs. Traditional single-stage approaches may use certain body
      measurements or explanatory variables to predict the BFP. Diverging from existing
      approaches, this study proposes new intelligent hybrid approaches to obtain fewer
      explanatory variables, and the proposed forecasting models are able to
      effectively predict the BFP. The proposed hybrid models consist of multiple
      regression (MR), artificial neural network (ANN), multivariate adaptive
      regression splines (MARS), and support vector regression (SVR) techniques. The
      first stage of the modeling includes the use of MR and MARS to obtain fewer but
      more important sets of explanatory variables. In the second stage, the remaining
      important variables are served as inputs for the other forecasting methods. A
      real dataset was used to demonstrate the development of the proposed hybrid
      models. The prediction results revealed that the proposed hybrid schemes
      outperformed the typical, single-stage forecasting models. 

PMID- 24723805
TI  - VIM-based dynamic sparse grid approach to partial differential equations.
AB  - Combining the variational iteration method (VIM) with the sparse grid theory, a
      dynamic sparse grid approach for nonlinear PDEs is proposed in this paper. In
      this method, a multilevel interpolation operator is constructed based on the
      sparse grids theory firstly. The operator is based on the linear combination of
      the basic functions and independent of them. Second, by means of the precise
      integration method (PIM), the VIM is developed to solve the nonlinear system of
      ODEs which is obtained from the discretization of the PDEs. In addition, a
      dynamic choice scheme on both of the inner and external grid points is proposed.
      It is different from the traditional interval wavelet collocation method in which
      the choice of both of the inner and external grid points is dynamic. The
      numerical experiments show that our method is better than the traditional wavelet
      collocation method, especially in solving the PDEs with the Nuemann boundary
      conditions. 

PMID- 24723806
TI  - Decomposition-based multiobjective evolutionary algorithm for community detection
      in dynamic social networks.
AB  - Community structure is one of the most important properties in social networks.
      In dynamic networks, there are two conflicting criteria that need to be
      considered. One is the snapshot quality, which evaluates the quality of the
      community partitions at the current time step. The other is the temporal cost,
      which evaluates the difference between communities at different time steps. In
      this paper, we propose a decomposition-based multiobjective community detection
      algorithm to simultaneously optimize these two objectives to reveal community
      structure and its evolution in dynamic networks. It employs the framework of
      multiobjective evolutionary algorithm based on decomposition to simultaneously
      optimize the modularity and normalized mutual information, which quantitatively
      measure the quality of the community partitions and temporal cost, respectively.
      A local search strategy dealing with the problem-specific knowledge is
      incorporated to improve the effectiveness of the new algorithm. Experiments on
      computer-generated and real-world networks demonstrate that the proposed
      algorithm can not only find community structure and capture community evolution
      more accurately, but also be steadier than the two compared algorithms. 

PMID- 24723807
TI  - Protocol independent adaptive route update for VANET.
AB  - High relative node velocity and high active node density have presented
      challenges to existing routing approaches within highly scaled ad hoc wireless
      networks, such as Vehicular Ad hoc Networks (VANET). Efficient routing requires
      finding optimum route with minimum delay, updating it on availability of a better
      one, and repairing it on link breakages. Current routing protocols are generally
      focused on finding and maintaining an efficient route, with very less emphasis on
      route update. Adaptive route update usually becomes impractical for dense
      networks due to large routing overheads. This paper presents an adaptive route
      update approach which can provide solution for any baseline routing protocol. The
      proposed adaptation eliminates the classification of reactive and proactive by
      categorizing them as logical conditions to find and update the route. 

PMID- 24723808
TI  - A modified implementation of tristate inverter based static master-slave flip
      flop with improved power-delay-area product.
AB  - The paper introduces novel architectures for implementation of fully static
      master-slave flip-flops for low power, high performance, and high density. Based
      on the proposed structure, traditional C(2)MOS latch (tristate inverter/clocked
      inverter) based flip-flop is implemented with fewer transistors. The modified
      C(2)MOS based flip-flop designs mC(2)MOSff1 and mC(2)MOSff2 are realized using
      only sixteen transistors each while the number of clocked transistors is also
      reduced in case of mC(2)MOSff1. Postlayout simulations indicate that mC(2)MOSff1
      flip-flop shows 12.4% improvement in PDAP (power-delay-area product) when
      compared with transmission gate flip-flop (TGFF) at 16X capacitive load which is
      considered to be the best design alternative among the conventional master-slave
      flip-flops. To validate the correct behaviour of the proposed design, an eight
      bit asynchronous counter is designed to layout level. LVS and parasitic
      extraction were carried out on Calibre, whereas layouts were implemented using IC
      station (Mentor Graphics). HSPICE simulations were used to characterize the
      transient response of the flip-flop designs in a 180 nm/1.8 V CMOS technology.
      Simulations were also performed at 130 nm, 90 nm, and 65 nm to reveal the
      scalability of both the designs at modern process nodes.

PMID- 24723810
TI  - On positive radial solutions for a class of elliptic equations.
AB  - A class of elliptic boundary value problem in an exterior domain is considered
      under some conditions concerning the first eigenvalue of the relevant linear
      operator, where the variables of nonlinear term f(s, u) need not to be separated.
      Several new theorems on the existence and multiplicity of positive radial
      solutions are obtained by means of fixed point index theory. Our conclusions are
      essential improvements of the results in Lan and Webb (1998), Lee (1997), Mao and
      Xue (2002), Stanczy (2000), and Han and Wang (2006). 

PMID- 24723809
TI  - The retrospective analysis of posterior short-segment pedicle instrumentation
      without fusion for thoracolumbar burst fracture with neurological deficit.
AB  - This study aims to investigate the efficacy of posterior short-segment pedicle
      instrumentation without fusion in curing thoracolumbar burst fracture. All of the
      53 patients were treated with short-segment pedicle instrumentation and
      laminectomy without fusion, and the restoration of retropulsed bone fragments was
      conducted by a novel custom-designed repositor (RRBF). The mean operation time
      and blood loss during surgery were analyzed; the radiological index and
      neurological status were compared before and after the operation. The mean
      operation time was 93 min (range: 62-110 min) and the mean intraoperative blood
      loss was 452 mL in all cases. The average canal encroachment was 50.04% and
      10.92% prior to the surgery and at last followup, respectively (P < 0.01). The
      preoperative kyphotic angle was 17.2 degree (+/- 6.87 degrees), whereas it
      decreased to 8.42 degree (+/- 4.99 degrees) at last followup (P < 0.01). Besides,
      the mean vertebral body height increased from 40.15% (+/- 9.40%) before surgery
      to 72.34% (+/- 12.32%) at last followup (P < 0.01). 45 patients showed 1-2 grades
      improvement in Frankel's scale at last followup. This technique allows for
      satisfactory canal clearance and restoration of vertebral body height and
      kyphotic angle, and it may promote the recovery of neurological function.
      However, further research is still necessary to confirm the efficacy of this
      treatment.

PMID- 24723811
TI  - Beta value coupled wave theory for nonslanted reflection gratings.
AB  - We present a modified coupled wave theory to describe the properties of
      nonslanted reflection volume diffraction gratings. The method is based on the
      beta value coupled wave theory, which will be corrected by using appropriate
      boundary conditions. The use of this correction allows predicting the efficiency
      of the reflected order for nonslanted reflection gratings embedded in two media
      with different refractive indices. The results obtained by using this method will
      be compared to those obtained using a matrix method, which gives exact solutions
      in terms of Mathieu functions, and also to Kogelnik's coupled wave theory. As
      will be demonstrated, the technique presented in this paper means a significant
      improvement over Kogelnik's coupled wave theory. 

PMID- 24723812
TI  - Efficient parallel implementation of active appearance model fitting algorithm on
      GPU.
AB  - The active appearance model (AAM) is one of the most powerful model-based object
      detecting and tracking methods which has been widely used in various situations.
      However, the high-dimensional texture representation causes very time-consuming
      computations, which makes the AAM difficult to apply to real-time systems. The
      emergence of modern graphics processing units (GPUs) that feature a many-core,
      fine-grained parallel architecture provides new and promising solutions to
      overcome the computational challenge. In this paper, we propose an efficient
      parallel implementation of the AAM fitting algorithm on GPUs. Our design idea is
      fine grain parallelism in which we distribute the texture data of the AAM, in
      pixels, to thousands of parallel GPU threads for processing, which makes the
      algorithm fit better into the GPU architecture. We implement our algorithm using
      the compute unified device architecture (CUDA) on the Nvidia's GTX 650 GPU, which
      has the latest Kepler architecture. To compare the performance of our algorithm
      with different data sizes, we built sixteen face AAM models of different
      dimensional textures. The experiment results show that our parallel AAM fitting
      algorithm can achieve real-time performance for videos even on very high
      dimensional textures. 

PMID- 24723813
TI  - 16QAM blind equalization via maximum entropy density approximation technique and
      nonlinear Lagrange multipliers.
AB  - Recently a new blind equalization method was proposed for the 16QAM constellation
      input inspired by the maximum entropy density approximation technique with
      improved equalization performance compared to the maximum entropy approach,
      Godard's algorithm, and others. In addition, an approximated expression for the
      minimum mean square error (MSE) was obtained. The idea was to find those Lagrange
      multipliers that bring the approximated MSE to minimum. Since the derivation of
      the obtained MSE with respect to the Lagrange multipliers leads to a nonlinear
      equation for the Lagrange multipliers, the part in the MSE expression that caused
      the nonlinearity in the equation for the Lagrange multipliers was ignored. Thus,
      the obtained Lagrange multipliers were not those Lagrange multipliers that bring
      the approximated MSE to minimum. In this paper, we derive a new set of Lagrange
      multipliers based on the nonlinear expression for the Lagrange multipliers
      obtained from minimizing the approximated MSE with respect to the Lagrange
      multipliers. Simulation results indicate that for the high signal to noise ratio
      (SNR) case, a faster convergence rate is obtained for a channel causing a high
      initial intersymbol interference (ISI) while the same equalization performance is
      obtained for an easy channel (initial ISI low). 

PMID- 24723814
TI  - Multistep-ahead air passengers traffic prediction with hybrid ARIMA-SVMs models.
AB  - The hybrid ARIMA-SVMs prediction models have been established recently, which
      take advantage of the unique strength of ARIMA and SVMs models in linear and
      nonlinear modeling, respectively. Built upon this hybrid ARIMA-SVMs models alike,
      this study goes further to extend them into the case of multistep-ahead
      prediction for air passengers traffic with the two most commonly used multistep
      ahead prediction strategies, that is, iterated strategy and direct strategy.
      Additionally, the effectiveness of data preprocessing approaches, such as
      deseasonalization and detrending, is investigated and proofed along with the two
      strategies. Real data sets including four selected airlines' monthly series were
      collected to justify the effectiveness of the proposed approach. Empirical
      results demonstrate that the direct strategy performs better than iterative one
      in long term prediction case while iterative one performs better in the case of
      short term prediction. Furthermore, both deseasonalization and detrending can
      significantly improve the prediction accuracy for both strategies, indicating the
      necessity of data preprocessing. As such, this study contributes as a full
      reference to the planners from air transportation industries on how to tackle
      multistep-ahead prediction tasks in the implementation of either prediction
      strategy. 

PMID- 24723815
TI  - An efficient sonochemical synthesis of novel Schiff's bases, thiazolidine, and
      pyrazolidine incorporating 1,8-naphthyridine moiety and their cytotoxic activity
      against HePG2 cell lines.
AB  - Novel Schiff's bases 4a-e, 5a, 5b, and 6, thiazolidine 7a-d, and pyrazolidine 8
      have been synthesized using the versatile synthon 4-hydroxy-2,7-dimethyl-1,8
      naphthyridine 1. Reactions carried out under ultrasound irradiation showed higher
      rates and yields than those done under silent conditions. The newly synthesized
      compounds were evaluated for HepG2 cell growth inhibition. The results obtained
      revealed that the tested compounds possess inhibitory effect on the growth of
      HepG2 liver cancer cells. The results were compared to doxorubicin as a reference
      drug (IC50: 0.04). Compounds 4a and 7b showed the highest inhibition activity
      against the HepG2 cell line (IC50: 0.047 and 0.041 uM, resp.) among all the
      tested compounds.

PMID- 24723816
TI  - Characterization of developmental- and stress-mediated expression of cinnamoyl
      CoA reductase in kenaf (Hibiscus cannabinus L.).
AB  - Cinnamoyl-CoA reductase (CCR) is an important enzyme for lignin biosynthesis as
      it catalyzes the first specific committed step in monolignol biosynthesis. We
      have cloned a full length coding sequence of CCR from kenaf (Hibiscus cannabinus
      L.), which contains a 1,020-bp open reading frame (ORF), encoding 339 amino acids
      of 37.37 kDa, with an isoelectric point (pI) of 6.27 (JX524276, HcCCR2). BLAST
      result found that it has high homology with other plant CCR orthologs. Multiple
      alignment with other plant CCR sequences showed that it contains two highly
      conserved motifs: NAD(P) binding domain (VTGAGGFIASWMVKLLLEKGY) at N-terminal and
      probable catalytic domain (NWYCYGK). According to phylogenetic analysis, it was
      closely related to CCR sequences of Gossypium hirsutum (ACQ59094) and Populus
      trichocarpa (CAC07424). HcCCR2 showed ubiquitous expression in various kenaf
      tissues and the highest expression was detected in mature flower. HcCCR2 was
      expressed differentially in response to various stresses, and the highest
      expression was observed by drought and NaCl treatments. 

PMID- 24723817
TI  - Use of a digital camera to monitor the growth and nitrogen status of cotton.
AB  - The main objective of this study was to develop a nondestructive method for
      monitoring cotton growth and N status using a digital camera. Digital images were
      taken of the cotton canopies between emergence and full bloom. The green and red
      values were extracted from the digital images and then used to calculate canopy
      cover. The values of canopy cover were closely correlated with the normalized
      difference vegetation index and the ratio vegetation index and were measured
      using a GreenSeeker handheld sensor. Models were calibrated to describe the
      relationship between canopy cover and three growth properties of the cotton crop
      (i.e., aboveground total N content, LAI, and aboveground biomass). There were
      close, exponential relationships between canopy cover and three growth
      properties. And the relationships for estimating cotton aboveground total N
      content were most precise, the coefficients of determination (R(2)) value was
      0.978, and the root mean square error (RMSE) value was 1.479 g m(-2). Moreover,
      the models were validated in three fields of high-yield cotton. The result
      indicated that the best relationship between canopy cover and aboveground total N
      content had an R(2) value of 0.926 and an RMSE value of 1.631 g m(-2). In
      conclusion, as a near-ground remote assessment tool, digital cameras have good
      potential for monitoring cotton growth and N status.

PMID- 24723818
TI  - Behavior identification based on geotagged photo data set.
AB  - The popularity of mobile devices has produced a set of image data with geographic
      information, time information, and text description information, which is called
      geotagged photo data set. The division of this kind of data by its behavior and
      the location not only can identify the user's important location and daily
      behavior, but also helps users to sort the huge image data. This paper proposes a
      method to build an index based on multiple classification result, which can
      divide the data set multiple times and distribute labels to the data to build
      index according to the estimated probability of classification results in order
      to accomplish the identification of users' important location and daily
      behaviors. This paper collects 1400 discrete sets of data as experimental data to
      verify the method proposed in this paper. The result of the experiment shows that
      the index and actual tagging results have a high inosculation. 

PMID- 24723819
TI  - Efficacy of combined formulations of fungicides with different modes of action in
      controlling botrytis gray mold disease in chickpea.
AB  - Botrytis gray mold (BGM) caused by Botrytis cinerea Pers. Ex. Fr. is an extremely
      devastating disease of chickpea (Cicer arietinum L.) and has a regional as well
      as an international perspective. Unfortunately, nonchemical methods for its
      control are weak and ineffective. In order to identify an effective control
      measure, six fungicides with different modes of action were evaluated on a BGM
      susceptible chickpea variety BARIchhola-1 at a high BGM incidence location
      (Madaripur) in Bangladesh for three years (2008, 2009, and 2010). Among the six
      fungicides tested, one was protectant [Vondozeb 42SC, a.i. mancozeb (0.2%)], two
      systemic [Bavistin 50 WP, a.i. carbendazim (0.2%), and Protaf 250EC,
      propiconazole (0.05%)], and three combination formulations [Acrobat MZ690,
      dimethomorph 9% + mancozeb 60%, (0.2%); Secure 600 WG, phenomadone + mancozeb
      (0.2%); and Companion, mancozeb 63% + carbendazim 12% (0.2%)]. The results showed
      superiority of combination formulations involving both protectant and systemic
      fungicides over the sole application of either fungicide separately. Among the
      combination fungicides, Companion was most effective, resulting in the lowest
      disease severity (3.33 score on 1-9 scale) and the highest increase (38%) of
      grain yield in chickpea. Therefore, this product could be preferred over the sole
      application of either solo protectant or systemic fungicides to reduce yield
      losses and avoid fungicide resistance.

PMID- 24723821
TI  - Neural network assisted inverse dynamic guidance for terminally constrained entry
      flight.
AB  - This paper presents a neural network assisted entry guidance law that is designed
      by applying Bezier approximation. It is shown that a fully constrained
      approximation of a reference trajectory can be made by using the Bezier curve.
      Applying this approximation, an inverse dynamic system for an entry flight is
      solved to generate guidance command. The guidance solution thus gotten ensures
      terminal constraints for position, flight path, and azimuth angle. In order to
      ensure terminal velocity constraint, a prediction of the terminal velocity is
      required, based on which, the approximated Bezier curve is adjusted. An
      artificial neural network is used for this prediction of the terminal velocity.
      The method enables faster implementation in achieving fully constrained entry
      flight. Results from simulations indicate improved performance of the neural
      network assisted method. The scheme is expected to have prospect for further
      research on automated onboard control of terminal velocity for both reentry and
      terminal guidance laws. 

PMID- 24723820
TI  - Screening of indigenous oxalate degrading lactic acid bacteria from human faeces
      and South Indian fermented foods: assessment of probiotic potential.
AB  - Lactic acid bacteria (LAB) have the potential to degrade intestinal oxalate and
      this is increasingly being studied as a promising probiotic solution to manage
      kidney stone disease. In this study, oxalate degrading LAB were isolated from
      human faeces and south Indian fermented foods, subsequently assessed for
      potential probiotic property in vitro and in vivo. Based on preliminary
      characteristics, 251 out of 673 bacterial isolates were identified as LAB. A
      total of 17 strains were found to degrade oxalate significantly between 40.38%
      and 62.90% and were subjected to acid and bile tolerance test. Among them, nine
      strains exhibited considerable tolerance up to pH 3.0 and at 0.3% bile. These
      were identified as Lactobacillus fermentum and Lactobacillus salivarius using 16S
      rDNA sequencing. Three strains, Lactobacillus fermentum TY5, Lactobacillus
      fermentum AB1, and Lactobacillus salivarius AB11, exhibited good adhesion to HT
      29 cells and strong antimicrobial activity. They also conferred resistance to
      kanamycin, rifampicin, and ampicillin, but were sensitive to chloramphenicol and
      erythromycin. The faecal recovery rate of these strains was observed as 15.16%
      (TY5), 6.71% (AB1), and 9.3% (AB11) which indicates the colonization ability. In
      conclusion, three efficient oxalate degrading LAB were identified and their
      safety assessments suggest that they may serve as good probiotic candidates for
      preventing hyperoxaluria. 

PMID- 24723822
TI  - Mesenteric lymph drainage alleviates acute kidney injury induced by hemorrhagic
      shock without resuscitation.
AB  - This study aimed to investigate the effect of mesenteric lymph drainage on the
      acute kidney injury induced by hemorrhagic shock without resuscitation. Eighteen
      male Wistar rats were randomly divided into sham, shock, and drainage groups. The
      hemorrhagic shock model (40 mmHg, 3 h) was established in shock and drainage
      groups; mesenteric lymph drainage was performed from 1 h to 3 h of hypotension in
      the drainage group. The results showed that renal tissue damage occurred; the
      levels of urea, creatinine, and trypsin in the plasma as well as intercellular
      adhesion molecule-1 (ICAM-1), receptor of advanced glycation end-products (RAGE),
      tumor necrosis factor-alpha (TNF-alpha), malondialdehyde (MDA), lactic acid (LA),
      and 2,3-DPG in the renal tissue were increased in the shock group after 3 h of
      hypotension. Mesenteric lymph drainage lessened the following: renal tissue
      damage; urea and trypsin concentrations in the plasma; ICAM-1, RAGE, TNF-alpha,
      MDA, and LA levels in the renal tissue. By contrast, mesenteric lymph drainage
      increased the 2,3-DPG level in the renal tissue. These findings indicated that
      mesenteric lymph drainage could relieve kidney injury caused by sustained
      hypotension, and its mechanisms involve the decrease in trypsin activity,
      suppression of inflammation, alleviation of free radical injury, and improvement
      of energy metabolism.

PMID- 24723823
TI  - Effects of water quality on dissolution of yerba mate extract powders.
AB  - Yerba mate tea is known as one of the most popular nonalcoholic beverages
      favoured by South Americans due to its nutrition facts and medicinal properties.
      The processing of yerba mate tea is found to affect the properties of its final
      forms. This study presents an investigation into the effects of water sources on
      the dissolution of yerba mate extract powders. Comparisons were conducted between
      yerba mate teas prepared by dissolving yerba mate extract powders into tap water
      and deionized water. Topics to be explored in this work are the major
      compositions and antioxidant activities, including total phenol content, reducing
      power, DPPH scavenging activity, and ABTS(+)* scavenging capacity. It is
      indicated that there is little difference for antioxidant activities and major
      constituents of yerba mate teas between both water sources. However, a deeper
      color is seen in the tap water case, resulting from the reaction between tannic
      acid and ions. This research finding can be treated as a way to benefit the yerba
      mate tea processing for applications. 

PMID- 24723824
TI  - Hydrothermal synthesis of nanostructured manganese oxide as cathodic catalyst in
      a microbial fuel cell fed with leachate.
AB  - Much effort has been devoted to the synthesis of novel nanostructured MnO2
      materials because of their unique properties and potential applications as
      cathode catalyst in Microbial fuel cell. Hybrid MnO2 nanostructures were
      fabricated by a simple hydrothermal method in this study. Their crystal
      structures, morphology, and electrochemical characters were carried out by FESEM,
      N2-adsorption-desorption, and CV, indicating that the hydrothermally synthesized
      MnO2 (HSM) was structured by nanorods of high aspect ratio and multivalve
      nanoflowers and more positive than the naturally synthesized MnO2 (NSM),
      accompanied by a noticeable increase in oxygen reduction peak current. When the
      HSM was employed as the cathode catalyst in air-cathode MFC which fed with
      leachate, a maximum power density of 119.07 mW/m(2) was delivered, 64.68% higher
      than that with the NSM as cathode catalyst. Furthermore, the HSM via a 4-e
      pathway, but the NSM via a 2-e pathway in alkaline solution, and as 4-e pathway
      is a more efficient oxygen reduction reaction, the HSM was more positive than
      NSM. Our study provides useful information on facile preparation of cost
      effective cathodic catalyst in air-cathode MFC for wastewater treatment.

PMID- 24723825
TI  - Benefits and harms of extending the duration of dual antiplatelet therapy after
      percutaneous coronary intervention with drug-eluting stents: a meta-analysis.
AB  - BACKGROUND: The optimal duration of dual antiplatelet therapy (DAPT) after
      percutaneous coronary intervention (PCI) is unclear. METHODS: We conducted a
      systematic review and meta-analysis of randomized controlled trials evaluating
      risk of adverse events in participants receiving different durations of DAPT
      following insertion of drug-eluting stents. RESULTS: Five trials were included,
      but only four had data suitable for meta-analysis (n = 8,231 participants). No
      significant increase in the composite endpoint of death and nonfatal myocardial
      infarction was observed with earlier cessation of DAPT in any instance when
      compared to longer durations of DAPT (RR 0.64 95% CI 0.25-1.63 for 3 versus 12
      months, RR 1.09 95% CI 0.84-1.41 for 6 versus 12 months and, RR 0.64 95% CI 0.35
      1.16 for 12 versus 24 months). Pooled results showed a significantly lower risk
      of major bleeding (RR 0.48 95% CI 0.25-0.93) and total bleeding (RR 0.30 95% CI
      0.16-0.54) for shorter compared to longer duration of DAPT. Subgroup analysis
      based on age, prior diabetes, and prior ACS failed to show any group where longer
      durations were consistently better than shorter ones. CONCLUSIONS: There are no
      cardiovascular or mortality benefits associated with extended duration of DAPT,
      but the risk of major bleeding was significantly lower with shorter lengths of
      therapy.

PMID- 24723826
TI  - Television time among Brazilian adolescents: correlated factors are different
      between boys and girls.
AB  - OBJECTIVE: The aim of this study was to identify the prevalence of excess
      television time and verify correlated factors in adolescent males and females.
      METHODS: This cross-sectional study included 2,105 adolescents aged from 13 to 18
      years from the city of Aracaju, Northeastern Brazil. Television time was self
      reported, corresponding to the time spent watching television in a typical week.
      Several correlates were examined including age, skin color, socioeconomic status,
      parent education, physical activity level, consumption of fruits and vegetables,
      smoking status, alcohol use, and sports team participation. RESULTS: The
      prevalence excess television time (>= 2 hours/day) in girls and boys was 70.9%
      and 66.2%, respectively. Girls with low socioeconomic status or inadequate
      consumption of fruits and vegetables were more likely to have excess television
      time. Among boys, those >16 years of age or with black skin color were more
      likely to have excess television time. CONCLUSIONS: Excess television time was
      observed in more than two-thirds of adolescents, being more evident in girls.
      Correlated factors differed according to sex. Efforts to reduce television time
      among Brazilian adolescents, and replace with more active pursuits, may yield
      desirable public health benefits.

PMID- 24723827
TI  - Improved particle swarm optimization with a collective local unimodal search for
      continuous optimization problems.
AB  - A new local search technique is proposed and used to improve the performance of
      particle swarm optimization algorithms by addressing the problem of premature
      convergence. In the proposed local search technique, a potential particle
      position in the solution search space is collectively constructed by a number of
      randomly selected particles in the swarm. The number of times the selection is
      made varies with the dimension of the optimization problem and each selected
      particle donates the value in the location of its randomly selected dimension
      from its personal best. After constructing the potential particle position, some
      local search is done around its neighbourhood in comparison with the current
      swarm global best position. It is then used to replace the global best particle
      position if it is found to be better; otherwise no replacement is made. Using
      some well-studied benchmark problems with low and high dimensions, numerical
      simulations were used to validate the performance of the improved algorithms.
      Comparisons were made with four different PSO variants, two of the variants
      implement different local search technique while the other two do not. Results
      show that the improved algorithms could obtain better quality solution while
      demonstrating better convergence velocity and precision, stability, robustness,
      and global-local search ability than the competing variants. 

PMID- 24723828
TI  - Application of electro-Fenton technology to remediation of polluted effluents by
      self-sustaining process.
AB  - The applicability of electro-Fenton technology to remediation of wastewater
      contaminated by several organic pollutants such as dyes and polycyclic aromatic
      hydrocarbons has been evaluated using iron-enriched zeolite as heterogeneous
      catalyst. The electro-Fenton technology is an advanced oxidation process that is
      efficient for the degradation of organic pollutants, but it suffers from the high
      operating costs due to the need for power investment. For this reason, in this
      study microbial fuel cells (MFCs) were designed in order to supply electricity to
      electro-Fenton processes and to achieve high treatment efficiency at low cost.
      Initially, the effect of key parameters on the MFC power generation was
      evaluated. Afterwards, the degradation of Reactive Black 5 dye and phenanthrene
      was evaluated in an electro-Fenton reactor, containing iron-enriched zeolite as
      catalyst, using the electricity supplied by the MFC. Near complete dye
      decolourization and 78% of phenanthrene degradation were reached after 90 min and
      30 h, respectively. Furthermore, preliminary reusability tests of the developed
      catalyst showed high degradation levels for successive cycles. The results permit
      concluding that the integrated system is adequate to achieve high treatment
      efficiency with low electrical consumption.

PMID- 24723829
TI  - In situ investigation of the 3D mechanical microstructure at nanoscale: nano-CT
      imaging method of local small region in large scale sample.
AB  - To investigate the local micro-/nanoscale region in a large scale sample, an
      image reconstruction method for nanometer computed tomography (nano-CT) was
      proposed in this paper. In the algorithm, wavelets were used to localize the
      filtered-backprojection (FBP) algorithm because of its space-frequency
      localization property. After the implementation of the algorithm, two simulation
      local reconstruction experiments were performed to confirm its effectiveness.
      Three evaluation criteria were used in the experiments to judge the quality of
      the reconstructed images. The experimental results showed that the algorithm
      proposed in this paper performed best because (1) the quality of its results had
      improved 20%-30% compared to the results of FBP and 10%-30% compared to the
      results of another wavelet algorithm; (2) the new algorithm was stable under
      different circumstances. Besides, an actual reconstruction experiment was
      performed using real projection data that had been collected in a CT experiment.
      Two-dimensional (2D) and three-dimensional (3D) images of the sample were
      reconstructed. The microstructure of the sample could be clearly observed in the
      reconstructed images. Since much attention has been directed towards the nano-CT
      technique to investigate the microstructure of materials, this new wavelet-based
      local tomography algorithm could be considered as a meaningful effort. 

PMID- 24723831
TI  - Formation of arbitrary patterns in ultraviolet cured polymer film via
      electrohydrodynamic patterning.
AB  - Electrohydrodynamic patterning of arbitrary patterns is achieved by optimizing
      the critical parameters (applied voltage and spacer height). The applied voltage
      has a great influence on the fidelity of L-shaped line structures with different
      sizes. The L-shaped line structures with high fidelity are obtained by using the
      moderate applied voltage. The spacer height has a great influence on the fidelity
      of square structures with different sizes. The square structures with high
      fidelity are obtained by using the low height spacer. The multi-field coupling
      transient finite element simulation demonstrates that the lack of polymer owing
      to the high height spacer leads to the formation of defects. 

PMID- 24723830
TI  - Effects of traditional Chinese medicine Shuxuetong injection on random skin flap
      survival in rats.
AB  - BACKGROUND: A Shuxuetong injection is traditionally used in Chinese medicine to
      treat "blood stasis and stagnation" (yu xue yu zhi). We investigated the effect
      of such injection on the survival of random skin flaps. METHODS: McFarlane flaps
      were established in 60 rats divided into two groups. Postoperative celiac
      injections were given to both groups for 7 days. Shuxuetong was injected into the
      test group, and saline was injected into controls. On day 7, tissues were stained
      with H&E (hematoxylin-eosin) stain, immunohistochemically evaluated, and the
      expression levels of xanthine oxidase were determined. RESULT: The mean area of
      flap survival in the test group was significantly higher than in controls.
      Expression of vascular endothelial growth factor and superoxide dismutase, and
      microvessel development, were markedly increased in the test group, and the
      malondialdehyde level was reduced. CONCLUSION: Shuxuetong promotes random skin
      flap survival.

PMID- 24723832
TI  - Bandwidth enhancement of a dual band planar monopole antenna using meandered
      microstrip feeding.
AB  - A meandered-microstrip fed circular shaped monopole antenna loaded with vertical
      slots on a high dielectric material substrate (epsilon r = 15) is proposed in
      this paper. The performance criteria of the proposed antenna have been
      experimentally verified by fabricating a printed prototype. The experimental
      results show that the proposed antenna has achieved wider bandwidth with
      satisfactory gain by introducing meandered-microstrip feeding in assistant of
      partial ground plane. It is observed that, the -10 dB impedance bandwidth of the
      proposed antenna at lower band is 44.4% (600 MHz-1 GHz) and at upper band is 28%
      (2.25 GHz-2.95 GHz). The measured maximum gains of -1.18 dBi and 4.87 dBi with
      maximum radiation efficiencies have been observed at lower band and upper band,
      respectively. The antenna configuration and parametric study have been carried
      out with the help of commercially available computer-aided EM simulator, and a
      good accordance is perceived in between the simulated and measured results. The
      analysis of performance criteria and almost consistent radiation pattern make the
      proposed antenna a suitable candidate for UHF RFID, WiMAX, and WLAN applications.

PMID- 24723833
TI  - Fate and distribution of heavy metals in wastewater irrigated calcareous soils.
AB  - Accumulation of heavy metals in Jordanian soils irrigated with treated wastewater
      threatens agricultural sustainability. This study was carried out to investigate
      the environmental fate of Zn, Ni, and Cd in calcareous soils irrigated with
      treated wastewater and to elucidate the impact of hydrous ferric oxide (HFO)
      amendment on metal redistribution among soil fractions. Results showed that
      sorption capacity for Zarqa River (ZR1) soil was higher than Wadi Dhuleil (WD1)
      soil for all metals. The order of sorption affinity for WD1 was in the decreasing
      order of Ni > Zn > Cd, consistent with electrostatic attraction and indication of
      weak association with soil constituents. Following metal addition, Zn and Ni were
      distributed among the carbonate and Fe/Mn oxide fractions, while Cd was
      distributed among the exchangeable and carbonate fractions in both soils.
      Amending soils with 3% HFO did not increase the concentration of metals
      associated with the Fe/Mn oxide fraction or impact metal redistribution. The
      study suggests that carbonates control the mobility and bioavailability of Zn,
      Ni, and Cd in these calcareous soils, even in presence of a strong adsorbent such
      as HFO. Thus, it can be inferred that in situ heavy metal remediation of these
      highly calcareous soils using iron oxide compounds could be ineffective. 

PMID- 24723834
TI  - Efficient constraint handling in electromagnetism-like algorithm for traveling
      salesman problem with time windows.
AB  - The traveling salesman problem with time windows (TSPTW) is a variant of the
      traveling salesman problem in which each customer should be visited within a
      given time window. In this paper, we propose an electromagnetism-like algorithm
      (EMA) that uses a new constraint handling technique to minimize the travel cost
      in TSPTW problems. The EMA utilizes the attraction-repulsion mechanism between
      charged particles in a multidimensional space for global optimization. This paper
      investigates the problem-specific constraint handling capability of the EMA
      framework using a new variable bounding strategy, in which real-coded particle's
      boundary constraints associated with the corresponding time windows of customers,
      is introduced and combined with the penalty approach to eliminate infeasibilities
      regarding time window violations. The performance of the proposed algorithm and
      the effectiveness of the constraint handling technique have been studied
      extensively, comparing it to that of state-of-the-art metaheuristics using
      several sets of benchmark problems reported in the literature. The results of the
      numerical experiments show that the EMA generates feasible and near-optimal
      results within shorter computational times compared to the test algorithms. 

PMID- 24723835
TI  - Design of a compact tuning fork-shaped notched ultrawideband antenna for wireless
      communication application.
AB  - A new compact planar notched ultrawideband (UWB) antenna is designed for wireless
      communication application. The proposed antenna has a compact size of 0.182lambda
      * 0.228lambda * 0.018lambda where lambda is the wavelength of the lowest
      operating frequency. The antenna is comprised of rectangular radiating patch,
      ground plane, and an arc-shaped strip in between radiating patch and feed line.
      By introducing a new Tuning Fork-shaped notch in the radiating plane, a stopband
      is obtained. The antenna is tested and measured. The measured result indicated
      that fabricated antenna has achieved a wide bandwidth of 4.33-13.8 GHz (at -10 dB
      return loss) with a rejection frequency band of 5.28-6.97 GHz (WiMAX, WLAN, and C
      band). The effects of the parameters of the antenna are discussed. The experiment
      results demonstrate that the proposed antenna can well meet the requirement for
      the UWB communication in spite of its compactness and small size.

PMID- 24723837
TI  - Stability of nonlinear Dirichlet BVPs governed by fractional Laplacian.
AB  - We consider a class of partial differential equations with the fractional
      Laplacian and the homogeneous Dirichlet boundary data. Some sufficient condition
      under which the solutions of the equations considered depend continuously on
      parameters is stated. The application of the results to some optimal control
      problem is presented. The methods applied in the paper make use of the
      variational structure of the problem. 

PMID- 24723836
TI  - Early left ventricular systolic and diastolic dysfunction in patients with newly
      diagnosed obstructive sleep apnoea and normal left ventricular ejection fraction.
AB  - The aim of the study was to evaluate whether obstructive sleep apnea (OSA)
      contributes directly to left ventricular (LV) diastolic and regional systolic
      dysfunction in newly diagnosed OSA with normal left ventricle ejection fraction.
      METHODS: 125 consecutive patients were prospectively enrolled in the study.
      Control group consisted of 78 asymptomatic age-matched healthy subjects who did
      not have any cardiovascular and respiratory diseases. All patients had undergone
      overnight polysomnography and standard transthoracic and tissue Doppler imaging
      echocardiogram. RESULTS: The E/A ratio and the peak E wave at mitral flow were
      significantly lower and the peak A wave at mitral flow was significantly higher
      in OSA patients compared with control subjects. Left ventricle isovolumetric
      relaxation time (IVRT) and mitral valve flow propagation (MVFP) were
      significantly longer in OSA patients than in controls. Tissue Doppler derived S'
      amplitude of lateral part at mitral valve (S'Lm) and E' wave amplitudes both at
      the lateral (E'Lm) and septal parts of the mitral valve (E'Sm) were significantly
      lower in OSA patients compared to controls. CONCLUSION: Newly diagnosed OSA
      patients with normal global LV function have significantly impaired diastolic
      function and regional longitudinal systolic function. OSA is independently
      associated with these changes in LV function.

PMID- 24723838
TI  - Three-dimensional dynamic analyses of track-embankment-ground system subjected to
      high speed train loads.
AB  - A three-dimensional finite element model was developed to investigate dynamic
      response of track-embankment-ground system subjected to moving loads caused by
      high speed trains. The track-embankment-ground systems such as the sleepers, the
      ballast, the embankment, and the ground are represented by 8-noded solid
      elements. The infinite elements are used to represent the infinite boundary
      condition to absorb vibration waves induced by the passing of train load at the
      boundary. The loads were applied on the rails directly to simulate the real
      moving loads of trains. The effects of train speed on dynamic response of the
      system are considered. The effect of material parameters, especially the modulus
      changes of ballast and embankment, is taken into account to demonstrate the
      effectiveness of strengthening the ballast, embankment, and ground for mitigating
      system vibration in detail. The numerical results show that the model is reliable
      for predicting the amplitude of vibrations produced in the track-embankment
      ground system by high-speed trains. Stiffening of fill under the embankment can
      reduce the vibration level, on the other hand, it can be realized by installing a
      concrete slab under the embankment. The influence of axle load on the vibration
      of the system is obviously lower than that of train speed. 

PMID- 24723839
TI  - Stability analysis of impulsive control systems with finite and infinite delays.
AB  - This paper studies impulsive control systems with finite and infinite delays.
      Several stability criteria are established by employing the largest and smallest
      eigenvalue of matrix. Our sufficient conditions are less restrictive than the
      ones in the earlier literature. Moreover, it is shown that by using impulsive
      control, the delay systems can be stabilized even if it contains no stable
      matrix. Finally, some numerical examples are discussed to illustrate the
      theoretical results. 

PMID- 24723840
TI  - Carbonate hydroxyapatite and silicon-substituted carbonate hydroxyapatite:
      synthesis, mechanical properties, and solubility evaluations.
AB  - The present study investigates the chemical composition, solubility, and physical
      and mechanical properties of carbonate hydroxyapatite (CO3Ap) and silicon
      substituted carbonate hydroxyapatite (Si-CO3Ap) which have been prepared by a
      simple precipitation method. X-ray diffraction (XRD), Fourier transform infrared
      spectroscopy (FTIR), X-ray fluorescence (XRF) spectroscopy, and inductively
      coupled plasma (ICP) techniques were used to characterize the formation of CO3Ap
      and Si-CO3Ap. The results revealed that the silicate (SiO4(4-)) and carbonate
      (CO3(2-)) ions competed to occupy the phosphate (PO4(3-)) site and also entered
      simultaneously into the hydroxyapatite structure. The Si-substituted CO3Ap
      reduced the powder crystallinity and promoted ion release which resulted in a
      better solubility compared to that of Si-free CO3Ap. The mean particle size of Si
      CO3Ap was much finer than that of CO3Ap. At 750 degrees C heat-treatment
      temperature, the diametral tensile strengths (DTS) of Si-CO3Ap and CO3Ap were
      about 10.8 +/- 0.3 and 11.8 +/- 0.4 MPa, respectively.

PMID- 24723841
TI  - Effects of igneous intrusion on microporosity and gas adsorption capacity of
      coals in the Haizi Mine, China.
AB  - This paper describes the effects of igneous intrusions on pore structure and
      adsorption capacity of the Permian coals in the Huaibei Coalfield, China. Twelve
      coal samples were obtained at different distances from a ~120 m extremely thick
      sill. Comparisons were made between unaltered and heat-affected coals using
      geochemical data, pore-fracture characteristics, and adsorption properties.
      Thermal alteration occurs down to ~1.3 * sill thickness. Approaching the sill,
      the vitrinite reflectance (R(o)) increased from 2.30% to 2.78%, forming
      devolatilization vacuoles and a fine mosaic texture. Volatile matter (VM)
      decreased from 17.6% to 10.0% and the moisture decreased from 3.0% to 1.6%. With
      decreasing distance to the sill, the micropore volumes initially increased from
      0.0054 cm(3)/g to a maximum of 0.0146 cm(3)/g and then decreased to 0.0079
      cm(3)/g. The results show that the thermal evolution of the sill obviously
      changed the coal geochemistry and increased the micropore volume and adsorption
      capacity of heat-affected coal (60-160 m from the sill) compared with the
      unaltered coals. The trap effect of the sill prevented the high-pressure gas from
      being released, forming gas pocket. Mining activities near the sill created a low
      pressure zone leading to the rapid accumulation of methane and gas outbursts in
      the Haizi Mine.

PMID- 24723842
TI  - An expert fitness diagnosis system based on elastic cloud computing.
AB  - This paper presents an expert diagnosis system based on cloud computing. It
      classifies a user's fitness level based on supervised machine learning
      techniques. This system is able to learn and make customized diagnoses according
      to the user's physiological data, such as age, gender, and body mass index (BMI).
      In addition, an elastic algorithm based on Poisson distribution is presented to
      allocate computation resources dynamically. It predicts the required resources in
      the future according to the exponential moving average of past observations. The
      experimental results show that Naive Bayes is the best classifier with the
      highest accuracy (90.8%) and that the elastic algorithm is able to capture
      tightly the trend of requests generated from the Internet and thus assign
      corresponding computation resources to ensure the quality of service. 

PMID- 24723843
TI  - Performance of Nonlinear Finite-Difference Poisson-Boltzmann Solvers.
AB  - We implemented and optimized seven finite-difference solvers for the full
      nonlinear Poisson-Boltzmann equation in biomolecular applications, including four
      relaxation methods, one conjugate gradient method, and two inexact Newton
      methods. The performance of the seven solvers was extensively evaluated with a
      large number of nucleic acids and proteins. Worth noting is the inexact Newton
      method in our analysis. We investigated the role of linear solvers in its
      performance by incorporating the incomplete Cholesky conjugate gradient and the
      geometric multigrid into its inner linear loop. We tailored and optimized both
      linear solvers for faster convergence rate. In addition, we explored strategies
      to optimize the successive over-relaxation method to reduce its convergence
      failures without too much sacrifice in its convergence rate. Specifically we
      attempted to adaptively change the relaxation parameter and to utilize the
      damping strategy from the inexact Newton method to improve the successive over
      relaxation method. Our analysis shows that the nonlinear methods accompanied with
      a functional-assisted strategy, such as the conjugate gradient method and the
      inexact Newton method, can guarantee convergence in the tested molecules.
      Especially the inexact Newton method exhibits impressive performance when it is
      combined with highly efficient linear solvers that are tailored for its special
      requirement.

PMID- 24723844
TI  - A revised density function for molecular surface definition in continuum solvent
      models.
AB  - A revised density function is developed to define the molecular surface for the
      numerical Poisson-Boltzmann methods to achieve a better convergence and higher
      numerical stability. The new density function does not use any predefined
      functional form but is numerically optimized to reproduce the reaction field
      energies computed with the solvent excluded surface definition. An exhaustive
      search in the parameter space is utilized in the optimization using a wide-range
      training molecules including proteins, nucleic acids, and peptides in both folded
      and unfolded conformations. A cubic-spline function is introduced to guarantee
      good numerical behavior of the new density function. Our test results show that
      the average relative energy errors computed with the revised density function are
      uniformly lower than 1% for both training and test molecules with different sizes
      and conformations. Our transferability analysis shows that the performance of the
      new method is mostly size and conformation independent. A detailed analysis
      further shows that the numerical forces computed with the revised density
      function converge better with respect to the grid spacing and are numerically
      more stable in tested peptides.

PMID- 24723846
TI  - Functional neurogenesis in the adult hippocampus: then and now.

PMID- 24723845
TI  - Perinatal asphyxia: CNS development and deficits with delayed onset.
AB  - Perinatal asphyxia constitutes a prototype of obstetric complications occurring
      when pulmonary oxygenation is delayed or interrupted. The primary insult relates
      to the duration of the period lacking oxygenation, leading to death if not re
      established. Re-oxygenation leads to a secondary insult, related to a cascade of
      biochemical events required for restoring proper function. Perinatal asphyxia
      interferes with neonatal development, resulting in long-term deficits associated
      to mental and neurological diseases with delayed clinical onset, by mechanisms
      not yet clarified. In the experimental scenario, the effects observed long after
      perinatal asphyxia have been explained by overexpression of sentinel proteins,
      such as poly(ADP-ribose) polymerase-1 (PARP-1), competing for NAD(+) during re
      oxygenation, leading to the idea that sentinel protein inhibition constitutes a
      suitable therapeutic strategy. Asphyxia induces transcriptional activation of pro
      inflammatory factors, in tandem with PARP-1 overactivation, and pharmacologically
      induced PARP-1 inhibition also down-regulates the expression of proinflammatory
      cytokines. Nicotinamide has been proposed as a suitable PARP-1 inhibitor. Its
      effect has been studied in an experimental model of global hypoxia in rats. In
      that model, the insult is induced by immersing rat fetus into a water bath for
      various periods of time. Following asphyxia, the pups are delivered, treated, and
      nursed by surrogate dams, pending further experiments. Nicotinamide rapidly
      distributes into the brain following systemic administration, reaching steady
      state concentrations sufficient to inhibit PARP-1 activity for several hours,
      preventing several of the long-term consequences of perinatal asphyxia,
      supporting the idea that nicotinamide constitutes a lead for exploring compounds
      with similar or better pharmacological profiles. 

PMID- 24723847
TI  - ROS-GC interlocked Ca(2+)-sensor S100B protein signaling in cone photoreceptors:
      review.
AB  - Photoreceptor rod outer segment membrane guanylate cyclase (ROS-GC) is central to
      visual transduction; it generates cyclic GMP, the second messenger of the photon
      signal. Photoexcited rhodopsin initiates a biochemical cascade that leads to a
      drop in the intracellular level of cyclic GMP and closure of cyclic nucleotide
      gated ion channels. Recovery of the photoresponse requires resynthesis of cyclic
      GMP, typically by a pair of ROS-GCs, 1 and 2. In rods, ROS-GCs exist as complexes
      with guanylate cyclase activating proteins (GCAPs), which are Ca(2+)-sensing
      elements. There is a light-induced fall in intracellular Ca(2+). As Ca(2+)
      dissociates from GCAPs in the 20-200 nM range, ROS-GC activity rises to quicken
      the photoresponse recovery. GCAPs then progressively turn down ROS-GC activity as
      Ca(2+) and cyclic GMP levels return to baseline. To date, GCAPs mediate the only
      known mechanism of ROS-GC regulation in the photoreceptors. However, in mammalian
      cone outer segments, cone synapses and ON bipolar cells, another Ca(2+) sensor
      protein, S100B, complexes with ROS-GC1 and senses the Ca(2+) signal with a K1/2
      of 400 nM. Unlike GCAPs, S100B stimulates ROS-GC activity when Ca(2+) is bound.
      Thus, the ROS-GC system in cones functions as a Ca(2+) bimodal switch; with
      rising intracellular Ca(2+), its activity is first turned down by GCAPs and then
      turned up by S100B. This presentation provides a historical perspective on the
      role of S100B in the photoreceptors, offers a pictorial model for the "bimodal"
      operation of the ROS-GC switch and projects future tasks that are needed to
      understand its operation. Some accounts of this review have been adopted from the
      original publications of these authors. 

PMID- 24723848
TI  - Reduced synaptic activity in neuronal networks derived from embryonic stem cells
      of murine Rett syndrome model.
AB  - Neurodevelopmental diseases such as the Rett syndrome (RTT) have received renewed
      attention, since the mechanisms involved may underlie a broad range of
      neuropsychiatric disorders such as schizophrenia and autism. In vertebrates early
      stages in the functional development of neurons and neuronal networks are
      difficult to study. Embryonic stem cell-derived neurons provide an easily
      accessible tool to investigate neuronal differentiation and early network
      formation. We used in vitro cultures of neurons derived from murine embryonic
      stem cells missing the methyl-CpG-binding protein 2 (MECP2) gene (MeCP2-/y) and
      from wild type cells of the corresponding background. Cultures were assessed
      using whole-cell patch-clamp electrophysiology and immunofluorescence. We studied
      the functional maturation of developing neurons and the activity of the synaptic
      connections they formed. Neurons exhibited minor differences in the developmental
      patterns for their intrinsic parameters, such as resting membrane potential and
      excitability; with the MeCP2-/y cells showing a slightly accelerated development,
      with shorter action potential half-widths at early stages. There was no
      difference in the early phase of synapse development, but as the cultures
      matured, significant deficits became apparent, particularly for inhibitory
      synaptic activity. MeCP2-/y embryonic stem cell-derived neuronal cultures show
      clear developmental deficits that match phenotypes observed in slice preparations
      and thus provide a compelling tool to further investigate the mechanisms behind
      RTT pathophysiology. 

PMID- 24723850
TI  - Emerging bioinformatics approaches for analysis of NGS-derived coding and non
      coding RNAs in neurodegenerative diseases.
AB  - Neurodegenerative diseases in general and specifically late-onset Alzheimer's
      disease (LOAD) involve a genetically complex and largely obscure ensemble of
      causative and risk factors accompanied by complex feedback responses. The advent
      of "high-throughput" transcriptome investigation technologies such as microarray
      and deep sequencing is increasingly being combined with sophisticated statistical
      and bioinformatics analysis methods complemented by knowledge-based approaches
      such as Bayesian Networks or network and graph analyses. Together, such
      "integrative" studies are beginning to identify co-regulated gene networks linked
      with biological pathways and potentially modulating disease predisposition,
      outcome, and progression. Specifically, bioinformatics analyses of integrated
      microarray and genotyping data in cases and controls reveal changes in gene
      expression of both protein-coding and small and long regulatory RNAs; highlight
      relevant quantitative transcriptional differences between LOAD and non-demented
      control brains and demonstrate reconfiguration of functionally meaningful
      molecular interaction structures in LOAD. These may be measured as changes in
      connectivity in "hub nodes" of relevant gene networks (Zhang etal., 2013). We
      illustrate here the open analytical questions in the transcriptome investigation
      of neurodegenerative disease studies, proposing "ad hoc" strategies for the
      evaluation of differential gene expression and hints for a simple analysis of the
      non-coding RNA (ncRNA) part of such datasets. We then survey the emerging role of
      long ncRNAs (lncRNAs) in the healthy and diseased brain transcriptome and
      describe the main current methods for computational modeling of gene networks. We
      propose accessible modular and pathway-oriented methods and guidelines for
      bioinformatics investigations of whole transcriptome next generation sequencing
      datasets. We finally present methods and databases for functional interpretations
      of lncRNAs and propose a simple heuristic approach to visualize and represent
      physical and functional interactions of the coding and non-coding components of
      the transcriptome. Integrating in a functional and integrated vision coding and
      ncRNA analyses is of utmost importance for current and future analyses of
      neurodegenerative transcriptomes. 

PMID- 24723849
TI  - Modulatory mechanisms and multiple functions of somatodendritic A-type K (+)
      channel auxiliary subunits.
AB  - Auxiliary subunits are non-conducting, modulatory components of the multi-protein
      ion channel complexes that underlie normal neuronal signaling. They interact with
      the pore-forming alpha-subunits to modulate surface distribution, ion
      conductance, and channel gating properties. For the somatodendritic subthreshold
      A-type potassium (ISA) channel based on Kv4 alpha-subunits, two types of
      auxiliary subunits have been extensively studied: Kv channel-interacting proteins
      (KChIPs) and dipeptidyl peptidase-like proteins (DPLPs). KChIPs are cytoplasmic
      calcium-binding proteins that interact with intracellular portions of the Kv4
      subunits, whereas DPLPs are type II transmembrane proteins that associate with
      the Kv4 channel core. Both KChIPs and DPLPs genes contain multiple start sites
      that are used by various neuronal populations to drive the differential
      expression of functionally distinct N-terminal variants. In turn, these N
      terminal variants generate tremendous functional diversity across the nervous
      system. Here, we focus our review on (1) the molecular mechanism underlying the
      unique properties of different N-terminal variants, (2) the shaping of native ISA
      properties by the concerted actions of KChIPs and DPLP variants, and (3) the
      surprising ways that KChIPs and DPLPs coordinate the activity of multiple
      channels to fine-tune neuronal excitability. Unlocking the unique contributions
      of different auxiliary subunit N-terminal variants may provide an important
      opportunity to develop novel targeted therapeutics to treat numerous neurological
      disorders. 

PMID- 24723852
TI  - Dynamical criticality during induction of anesthesia in human ECoG recordings.
AB  - In this work we analyze electro-corticography (ECoG) recordings in human subjects
      during induction of anesthesia with propofol. We hypothesize that the decrease in
      responsiveness that defines the anesthetized state is concomitant with the
      stabilization of neuronal dynamics. To test this hypothesis, we performed a
      moving vector autoregressive analysis and quantified stability of neuronal
      dynamics using eigenmode decomposition of the autoregressive matrices,
      independently fitted to short sliding temporal windows. Consistent with the
      hypothesis we show that while the subject is awake, many modes of neuronal
      activity oscillations are found at the edge of instability. As the subject
      becomes anesthetized, we observe statistically significant increase in the
      stability of neuronal dynamics, most prominently observed for high frequency
      oscillations. Stabilization was not observed in phase randomized surrogates
      constructed to preserve the spectral signatures of each channel of neuronal
      activity. Thus, stability analysis offers a novel way of quantifying changes in
      neuronal activity that characterize loss of consciousness induced by general
      anesthetics. 

PMID- 24723853
TI  - Different roles of axon guidance cues and patterned spontaneous activity in
      establishing receptive fields in the mouse superior colliculus.
AB  - Visual neurons in the superior colliculus (SC) respond to both bright (On) and
      dark (Off) stimuli in their receptive fields. This receptive field property is
      due to proper convergence of On- and Off-centered retinal ganglion cells to their
      target cells in the SC. In this study, we have compared the receptive field
      structure of individual SC neurons in two lines of mutant mice that are deficient
      in retinotopic mapping: the ephrin-A knockouts that lack important
      retinocollicular axonal guidance cues and the nAChR-beta2 knockouts that have
      altered activity-dependent refinement of retinocollicular projections. We find
      that even though the receptive fields are much larger in the ephrin-A knockouts,
      their On-Off overlap remains unchanged. These neurons also display normal level
      of selectivity for stimulus direction and orientation. In contrast, the On-Off
      overlap is disrupted in the beta2 knockouts. Together with the previous finding
      of disrupted direction and orientation selectivity in the beta2 knockout mice,
      our results indicate that molecular guidance cues and activity-dependent
      processes play different roles in the development of receptive field properties
      in the SC. 

PMID- 24723854
TI  - Delta-subunit-containing GABAA-receptors mediate tonic inhibition in paracapsular
      cells of the mouse amygdala.
AB  - The intercalated paracapsular cells (pcs) are small GABAergic interneurons that
      form densely populated clusters surrounding the basolateral (BLA) complex of the
      amygdala. Their main task in the amygdala circuitry appears to be the control of
      information flow, as they act as an inhibitory interface between input and output
      nuclei. Modulation of their activity is thus thought to affect amygdala output
      and the generation of fear and anxiety. Recent evidence indicates that pcs
      express benzodiazepine (BZ)-sensitive GABAA receptor (GABAAR) variants containing
      the alpha2- and alpha3-subunit for transmission of post-synaptic currents, yet
      little is known about the expression of extrasynaptic GABAARs, mediating tonic
      inhibition and regulating neuronal excitability. Here, we show that pcs from the
      lateral and medial intercalated cell cluster (l- and mITC, respectively) express
      a tonic GABAergic conductance that could be significantly increased in a
      concentration-dependent manner by the delta-preferring GABAAR agonist THIP (0.5
      10 MUM), but not by the BZ diazepam (1 MUM). The neurosteroid THDOC (300 nM) also
      increased tonic currents in pcs significantly, but only in the presence of
      additional GABA (5 MUM). Immunohistochemical stainings revealed that both the
      delta-GABAAR and the alpha4-GABAAR subunit are expressed throughout all ITCs,
      while no staining for the alpha5-GABAAR subunit could be detected. Moreover, 1
      MUM THIP dampened excitability in pcs most likely by increasing shunting
      inhibition. In line with this, THIP significantly decreased lITC-generated
      inhibition in target cells residing in the BLA nucleus by 30%. Taken together
      these results demonstrate for the first time that pcs express a tonic inhibitory
      conductance mediated most likely by alpha4/delta-containing GABAARs. This data
      also suggest that delta-GABAAR targeting compounds might possibly interfere with
      pcs-related neuronal processes such as fear extinction. 

PMID- 24723855
TI  - Neuronal activity (c-Fos) delineating interactions of the cerebral cortex and
      basal ganglia.
AB  - The cerebral cortex and basal ganglia (BG) form a neural circuit that is
      disrupted in disorders such as Parkinson's disease. We found that neuronal
      activity (c-Fos) in the BG followed cortical activity, i.e., high in arousal
      state and low in sleep state. To determine if cortical activity is necessary for
      BG activity, we administered atropine to rats to induce a dissociative state
      resulting in slow-wave electroencephalography but hyperactive motor behaviors.
      Atropine blocked c-Fos expression in the cortex and BG, despite high c-Fos
      expression in the sub-cortical arousal neuronal groups and thalamus, indicating
      that cortical activity is required for BG activation. To identify which glutamate
      receptors in the BG that mediate cortical inputs, we injected ketamine [N-methyl
      d-aspartate (NMDA) receptor antagonist] and 6-cyano-nitroquinoxaline-2, 3-dione
      (CNQX, a non-NMDA receptor antagonist). Systemic ketamine and CNQX administration
      revealed that NMDA receptors mediated subthalamic nucleus (STN) input to internal
      globus pallidus (GPi) and substantia nigra pars reticulata (SNr), while non-NMDA
      receptor mediated cortical input to the STN. Both types of glutamate receptors
      were involved in mediating cortical input to the striatum. Dorsal striatal
      (caudoputamen, CPu) dopamine depletion by 6-hydroxydopamine resulted in reduced
      activity of the CPu, globus pallidus externa (GPe), and STN but increased
      activity of the GPi, SNr, and putative layer V neurons in the motor cortex. Our
      results reveal that the cortical activity is necessary for BG activity and
      clarifies the pathways and properties of the BG-cortical network and their
      putative role in the pathophysiology of BG disorders. 

PMID- 24723851
TI  - GABAergic synapses: their plasticity and role in sensory cortex.
AB  - The mammalian neocortex is composed of a variety of cell types organized in a
      highly interconnected circuit. GABAergic neurons account for only about 20% of
      cortical neurons. However, they show widespread connectivity and a high degree of
      diversity in morphology, location, electrophysiological properties and gene
      expression. In addition, distinct populations of inhibitory neurons have
      different sensory response properties, capacities for plasticity and
      sensitivities to changes in sensory experience. In this review we summarize
      experimental evidence regarding the properties of GABAergic neurons in primary
      sensory cortex. We will discuss how distinct GABAergic neurons and different
      forms of GABAergic inhibitory plasticity may contribute to shaping sensory
      cortical circuit activity and function. 

PMID- 24723856
TI  - Cannabinoid, melanocortin and opioid receptor expression on DRD1 and DRD2
      subpopulations in rat striatum.
AB  - The striatum harbors two neuronal populations that enable action selection. One
      population represents the striatonigral pathway, expresses the dopamine receptor
      D1 (DRD1) and promotes the execution of motor programs, while the other
      population represents the striatopallidal pathway, expresses the dopamine
      receptor D2 (DRD2) and suppresses voluntary activity. The two populations
      integrate distinct sensorimotor, cognitive, and emotional information streams and
      their combined activity enables the selection of adaptive behaviors.
      Characterization of these populations is critical to the understanding of their
      role in action selection, because it aids the identification of the molecular
      mechanisms that separate them. To that end, we used fluorescent in situ
      hybridization to quantify the percentage of striatal cells that (co)express
      dopaminergic receptors and receptors of the cannabinoid, melanocortin or opioid
      neurotransmitters systems. Our main findings are that the cannabinoid 1 receptor
      is equally expressed on both populations with a gradient from dorsal to ventral
      striatum, that the opioid receptors have a preference for expression with either
      the DRD1 or DRD2 and that the melanocortin 4 receptor (MC4R) is predominantly
      expressed in ventral parts of the striatum. In addition, we find that the level
      of MC4R expression determines its localization to either the DRD1 or the DRD2
      population. Thereby, we provide insight into the sensitivity of the two
      dopaminoceptive populations to these neurotransmitters and progress the
      understanding of the mechanisms that enable action selection. 

PMID- 24723857
TI  - Evolution of the human brain: when bigger is better.
AB  - Comparative studies of the brain in mammals suggest that there are general
      architectural principles governing its growth and evolutionary development. We
      are beginning to understand the geometric, biophysical and energy constraints
      that have governed the evolution and functional organization of the brain and its
      underlying neuronal network. The object of this review is to present current
      perspectives on primate brain evolution, especially in humans, and to examine
      some hypothetical organizing principles that underlie the brain's complex
      organization. Some of the design principles and operational modes that underlie
      the information processing capacity of the cerebral cortex in primates will be
      explored. It is shown that the development of the cortex coordinates folding with
      connectivity in a way that produces smaller and faster brains, then otherwise
      would have been possible. In view of the central importance placed on brain
      evolution in explaining the success of our own species, one may wonder whether
      there are physical limits that constrain its processing power and evolutionary
      potential. It will be argued that at a brain size of about 3500 cm(3),
      corresponding to a brain volume two to three times that of modern man, the brain
      seems to reach its maximum processing capacity. The larger the brain grows beyond
      this critical size, the less efficient it will become, thus limiting any
      improvement in cognitive power. 

PMID- 24723859
TI  - Navigational strategies underlying phototaxis in larval zebrafish.
AB  - Understanding how the brain transforms sensory input into complex behavior is a
      fundamental question in systems neuroscience. Using larval zebrafish, we study
      the temporal component of phototaxis, which is defined as orientation decisions
      based on comparisons of light intensity at successive moments in time. We
      developed a novel "Virtual Circle" assay where whole-field illumination is
      abruptly turned off when the fish swims out of a virtually defined circular
      border, and turned on again when it returns into the circle. The animal receives
      no direct spatial cues and experiences only whole-field temporal light changes.
      Remarkably, the fish spends most of its time within the invisible virtual border.
      Behavioral analyses of swim bouts in relation to light transitions were used to
      develop four discrete temporal algorithms that transform the binary visual input
      (uniform light/uniform darkness) into the observed spatial behavior. In these
      algorithms, the turning angle is dependent on the behavioral history immediately
      preceding individual turning events. Computer simulations show that the
      algorithms recapture most of the swim statistics of real fish. We discovered that
      turning properties in larval zebrafish are distinctly modulated by temporal step
      functions in light intensity in combination with the specific motor history
      preceding these turns. Several aspects of the behavior suggest memory usage of up
      to 10 swim bouts (~10 sec). Thus, we show that a complex behavior like spatial
      navigation can emerge from a small number of relatively simple behavioral
      algorithms. 

PMID- 24723860
TI  - How a face may affect object-based attention: evidence from adults and 8-month
      old infants.
AB  - Object-based attention operates on perceptual objects, opening the possibility
      that the costs and benefits humans have to pay to move attention between-objects
      might be affected by the nature of the stimuli. The current study reported two
      experiments with adults and 8-month-old infants investigating whether object
      based-attention is affected by the type of stimulus (faces vs. non-faces
      stimuli). Using the well-known cueing task developed by Egly et al. (1994) to
      study the object-based component of attention, in Experiment 1 adult participants
      were presented with two upright, inverted or scrambled faces and an eye-tracker
      measured their saccadic latencies to find a target that could appear on the same
      object that was just cued or on the other object that was uncued. Data showed
      that an object-based effect (a smaller cost to shift attention within- compared
      to between-objects) occurred only with scrambled face, but not with upright or
      inverted faces. In Experiment 2 the same task was performed with 8-month-old
      infants, using upright and inverted faces. Data revealed that an object-based
      effect emerges only for inverted faces but not for upright faces. Overall, these
      findings suggest that object-based attention is modulated by the type of stimulus
      and by the experience acquired by the viewer with different objects. 

PMID- 24723858
TI  - Retrograde labeling, transduction, and genetic targeting allow cellular analysis
      of corticospinal motor neurons: implications in health and disease.
AB  - Corticospinal motor neurons (CSMN) have a unique ability to receive, integrate,
      translate, and transmit the cerebral cortex's input toward spinal cord targets
      and therefore act as a "spokesperson" for the initiation and modulation of
      voluntary movements that require cortical input. CSMN degeneration has an immense
      impact on motor neuron circuitry and is one of the underlying causes of numerous
      neurodegenerative diseases, such as primary lateral sclerosis (PLS), hereditary
      spastic paraplegia (HSP), and amyotrophic lateral sclerosis (ALS). In addition,
      CSMN death results in long-term paralysis in spinal cord injury patients.
      Detailed cellular analyses are crucial to gain a better understanding of the
      pathologies underlying CSMN degeneration. However, visualizing and identifying
      these vulnerable neuron populations in the complex and heterogeneous environment
      of the cerebral cortex have proved challenging. Here, we will review recent
      developments and current applications of novel strategies that reveal the
      cellular and molecular basis of CSMN health and vulnerability. Such studies hold
      promise for building long-term effective treatment solutions in the near future. 

PMID- 24723861
TI  - Nociception and pain: lessons from optogenetics.
AB  - The process of pain perception begins in the periphery by activation of
      nociceptors. From here nociceptive signals are conveyed via the dorsal horn of
      the spinal cord to multiple brain regions, where pain is perceived. Despite great
      progress in pain research in recent years, many questions remain regarding
      nociceptive circuitry and behavior, in both acute nociception and chronic pain
      states. Techniques that allow for selective activation of neuronal subpopulations
      in vivo can provide a better understanding of these complex pathways. Here we
      review the studies to date that have employed novel optogenetic tools to improve
      our understanding of the pain pathway at the peripheral, spinal and supraspinal
      levels. 

PMID- 24723862
TI  - Endogenous cortisol levels are associated with an imbalanced striatal sensitivity
      to monetary versus non-monetary cues in pathological gamblers.
AB  - Pathological gambling is a behavioral addiction characterized by a chronic
      failure to resist the urge to gamble. It shares many similarities with drug
      addiction. Glucocorticoid hormones including cortisol are thought to play a key
      role in the vulnerability to addictive behaviors, by acting on the mesolimbic
      reward pathway. Based on our previous report of an imbalanced sensitivity to
      monetary versus non-monetary incentives in the ventral striatum of pathological
      gamblers (PGs), we investigated whether this imbalance was mediated by individual
      differences in endogenous cortisol levels. We used functional magnetic resonance
      imaging (fMRI) and examined the relationship between cortisol levels and the
      neural responses to monetary versus non-monetary cues, while PGs and healthy
      controls were engaged in an incentive delay task manipulating both monetary and
      erotic rewards. We found a positive correlation between cortisol levels and
      ventral striatal responses to monetary versus erotic cues in PGs, but not in
      healthy controls. This indicates that the ventral striatum is a key region where
      cortisol modulates incentive motivation for gambling versus non-gambling related
      stimuli in PGs. Our results extend the proposed role of glucocorticoid hormones
      in drug addiction to behavioral addiction, and help understand the impact of
      cortisol on reward incentive processing in PGs. 

PMID- 24723863
TI  - Temporal relation between top-down and bottom-up processing in lexical tone
      perception.
AB  - Speech perception entails both top-down processing that relies primarily on
      language experience and bottom-up processing that depends mainly on instant
      auditory input. Previous models of speech perception often claim that bottom-up
      processing occurs in an early time window, whereas top-down processing takes
      place in a late time window after stimulus onset. In this paper, we evaluated the
      temporal relation of both types of processing in lexical tone perception. We
      conducted a series of event-related potential (ERP) experiments that recruited
      Mandarin participants and adopted three experimental paradigms, namely dichotic
      listening, lexical decision with phonological priming, and semantic violation. By
      systematically analyzing the lateralization patterns of the early and late ERP
      components that are observed in these experiments, we discovered that: auditory
      processing of pitch variations in tones, as a bottom-up effect, elicited greater
      right hemisphere activation; in contrast, linguistic processing of lexical tones,
      as a top-down effect, elicited greater left hemisphere activation. We also found
      that both types of processing co-occurred in both the early (around 200 ms) and
      late (around 300-500 ms) time windows, which supported a parallel model of
      lexical tone perception. Unlike the previous view that language processing is
      special and performed by dedicated neural circuitry, our study have elucidated
      that language processing can be decomposed into general cognitive functions
      (e.g., sensory and memory) and share neural resources with these functions. 

PMID- 24723865
TI  - Neurobiological underpinnings of reward anticipation and outcome evaluation in
      gambling disorder.
AB  - Gambling disorder is characterized by persistent and recurrent maladaptive
      gambling behavior, which leads to clinically significant impairment or distress.
      The disorder is associated with dysfunctions in the dopamine system. The dopamine
      system codes reward anticipation and outcome evaluation. Reward anticipation
      refers to dopaminergic activation prior to reward, while outcome evaluation
      refers to dopaminergic activation after reward. This article reviews evidence of
      dopaminergic dysfunctions in reward anticipation and outcome evaluation in
      gambling disorder from two vantage points: a model of reward prediction and
      reward prediction error by Wolfram Schultz et al. and a model of "wanting" and
      "liking" by Terry E. Robinson and Kent C. Berridge. Both models offer important
      insights on the study of dopaminergic dysfunctions in addiction, and implications
      for the study of dopaminergic dysfunctions in gambling disorder are suggested. 

PMID- 24723864
TI  - Common mechanisms of pain and depression: are antidepressants also analgesics?
AB  - Neither pain, nor depression exist as independent phenomena per se, they are
      highly subjective inner states, formed by our brain and built on the bases of our
      experiences, cognition and emotions. Chronic pain is associated with changes in
      brain physiology and anatomy. It has been suggested that the neuronal activity
      underlying subjective perception of chronic pain may be divergent from the
      activity associated with acute pain. We will discuss the possible common
      pathophysiological mechanism of chronic pain and depression with respect to the
      default mode network of the brain, neuroplasticity and the effect of
      antidepressants on these two pathological conditions. The default mode network of
      the brain has an important role in the representation of introspective mental
      activities and therefore can be considered as a nodal point, common for both
      chronic pain and depression. Neuroplasticity which involves molecular, cellular
      and synaptic processes modifying connectivity between neurons and neuronal
      circuits can also be affected by pathological states such as chronic pain or
      depression. We suppose that pathogenesis of depression and chronic pain shares
      common negative neuroplastic changes in the central nervous system (CNS). The
      positive impact of antidepressants would result in a reduction of these
      pathological cellular/molecular processes and in the amelioration of symptoms,
      but it may also increase survival times and quality of life of patients with
      chronic cancer pain. 

PMID- 24723866
TI  - Lipid rafts: a signaling platform linking cholesterol metabolism to synaptic
      deficits in autism spectrum disorders.

PMID- 24723867
TI  - Optogenetic dissection of amygdala functioning.
AB  - Studies of amygdala functioning have occupied a significant place in the history
      of understanding how the brain controls behavior and cognition. Early work on the
      amygdala placed this small structure as a key component in the regulation of
      emotion and affective behavior. Over time, our understanding of its role in brain
      processes has expanded, as we have uncovered amygdala influences on memory,
      reward behavior, and overall functioning in many other brain regions. Studies
      have indicated that the amygdala has widespread connections with a variety of
      brain structures, from the prefrontal cortex to regions of the brainstem, that
      explain its powerful influence on other parts of the brain and behaviors mediated
      by those regions. Thus, many optogenetic studies have focused on harnessing the
      powers of this technique to elucidate the functioning of the amygdala in relation
      to motivation, fear, and memory as well as to determine how the amygdala
      regulates activity in other structures. For example, studies using optogenetics
      have examined how specific circuits within amygdala nuclei regulate anxiety.
      Other work has provided insight into how the basolateral and central amygdala
      nuclei regulate memory processing underlying aversive learning. Many experiments
      have taken advantage of optogenetics' ability to target either genetically
      distinct subpopulations of neurons or the specific projections from the amygdala
      to other brain regions. Findings from such studies have provided evidence that
      particular patterns of activity in basolateral amygdala (BLA) glutamatergic
      neurons are related to memory consolidation processes, while other work has
      indicated the critical nature of amygdala inputs to the prefrontal cortex and
      nucleus accumbens (NA) in regulating behavior dependent on those downstream
      structures. This review will examine the recent discoveries on amygdala
      functioning made through experiments using optogenetics, placing these findings
      in the context of the major questions in the field. 

PMID- 24723868
TI  - Understanding and accounting for relational context is critical for social
      neuroscience.
AB  - Scientists have increasingly turned to the brain and to neuroscience more
      generally to further an understanding of social and emotional judgments and
      behavior. Yet, many neuroscientists (certainly not all) do not consider the role
      of relational context. Moreover, most have not examined the impact of relational
      context in a manner that takes advantage of conceptual and empirical advances in
      relationship science. Here we emphasize that: (1) all social behavior takes
      place, by definition, within the context of a relationship (even if that
      relationship is a new one with a stranger), and (2) relational context shapes not
      only social thoughts, feelings, and behaviors, but also some seemingly non-social
      thoughts, feelings, and behaviors in profound ways. We define relational context
      and suggest that accounting for it in the design and interpretation of
      neuroscience research is essential to the development of a coherent,
      generalizable neuroscience of social behavior. We make our case in two ways: (a)
      we describe some existing neuroscience research in three substantive areas
      (perceiving and reacting to others' emotions, providing help, and receiving help)
      that already has documented the powerful impact of relational context. (b) We
      describe some other neuroscience research from these same areas that has not
      taken relational context into account. Then, using findings from social and
      personality psychology, we make a case that different results almost certainly
      would have been found had the research been conducted in a different relational
      context. We neither attempt to review all evidence that relational context shapes
      neuroscience findings nor to put forward a theoretical analysis of all the ways
      relational context ought to shape neuroscience findings. Our goal is simply to
      urge greater and more systematic consideration of relational context in
      neuroscientific research. 

PMID- 24723869
TI  - Self-, other-, and joint monitoring using forward models.
AB  - In the psychology of language, most accounts of self-monitoring assume that it is
      based on comprehension. Here we outline and develop the alternative account
      proposed by Pickering and Garrod (2013), in which speakers construct forward
      models of their upcoming utterances and compare them with the utterance as they
      produce them. We propose that speakers compute inverse models derived from the
      discrepancy (error) between the utterance and the predicted utterance and use
      that to modify their production command or (occasionally) begin anew. We then
      propose that comprehenders monitor other people's speech by simulating their
      utterances using covert imitation and forward models, and then comparing those
      forward models with what they hear. They use the discrepancy to compute inverse
      models and modify their representation of the speaker's production command, or
      realize that their representation is incorrect and may develop a new production
      command. We then discuss monitoring in dialogue, paying attention to sequential
      contributions, concurrent feedback, and the relationship between monitoring and
      alignment. 

PMID- 24723870
TI  - Predicting the unpredictable: critical analysis and practical implications of
      predictive anticipatory activity.
AB  - A recent meta-analysis of experiments from seven independent laboratories (n =
      26) indicates that the human body can apparently detect randomly delivered
      stimuli occurring 1-10 s in the future (Mossbridge etal., 2012). The key
      observation in these studies is that human physiology appears to be able to
      distinguish between unpredictable dichotomous future stimuli, such as emotional
      vs. neutral images or sound vs. silence. This phenomenon has been called
      presentiment (as in "feeling the future"). In this paper we call it predictive
      anticipatory activity (PAA). The phenomenon is "predictive" because it can
      distinguish between upcoming stimuli; it is "anticipatory" because the
      physiological changes occur before a future event; and it is an "activity"
      because it involves changes in the cardiopulmonary, skin, and/or nervous systems.
      PAA is an unconscious phenomenon that seems to be a time-reversed reflection of
      the usual physiological response to a stimulus. It appears to resemble
      precognition (consciously knowing something is going to happen before it does),
      but PAA specifically refers to unconscious physiological reactions as opposed to
      conscious premonitions. Though it is possible that PAA underlies the conscious
      experience of precognition, experiments testing this idea have not produced clear
      results. The first part of this paper reviews the evidence for PAA and examines
      the two most difficult challenges for obtaining valid evidence for it:
      expectation bias and multiple analyses. The second part speculates on possible
      mechanisms and the theoretical implications of PAA for understanding physiology
      and consciousness. The third part examines potential practical applications. 

PMID- 24723871
TI  - Both attention and prediction are necessary for adaptive neuronal tuning in
      sensory processing.
AB  - The brain as a proactive system processes sensory information under the top-down
      influence of attention and prediction. However, the relation between attention
      and prediction remains undetermined given the conflation of these two mechanisms
      in the literature. To evaluate whether attention and prediction are dependent of
      each other, and if so, how these two top-down mechanisms may interact in sensory
      processing, we orthogonally manipulated attention and prediction in a target
      detection task. Participants were instructed to pay attention to one of two
      interleaved stimulus streams of predictable/unpredictable tone frequency. We
      found that attention and prediction interacted on the amplitude of the N1 ERP
      component. The N1 amplitude in the attended/predictable condition was larger than
      that in any of the other conditions. Dipole source localization analysis showed
      that the effect came from the activation in bilateral auditory areas. No
      significant effect was found in the P2 time window. Our results suggest that
      attention and prediction are dependent of each other. While attention might
      determine the overall cortical responsiveness to stimuli when prediction is
      involved, prediction might provide an anchor for the modulation of the synaptic
      input strengths which needs to be operated on the basis of attention. 

PMID- 24723872
TI  - A formal model of interpersonal inference.
AB  - INTRODUCTION: We propose that active Bayesian inference-a general framework for
      decision-making-can equally be applied to interpersonal exchanges. Social
      cognition, however, entails special challenges. We address these challenges
      through a novel formulation of a formal model and demonstrate its psychological
      significance. METHOD: We review relevant literature, especially with regards to
      interpersonal representations, formulate a mathematical model and present a
      simulation study. The model accommodates normative models from utility theory and
      places them within the broader setting of Bayesian inference. Crucially, we endow
      people's prior beliefs, into which utilities are absorbed, with preferences of
      self and others. The simulation illustrates the model's dynamics and furnishes
      elementary predictions of the theory. RESULTS: (1) Because beliefs about self and
      others inform both the desirability and plausibility of outcomes, in this
      framework interpersonal representations become beliefs that have to be actively
      inferred. This inference, akin to "mentalizing" in the psychological literature,
      is based upon the outcomes of interpersonal exchanges. (2) We show how some well
      known social-psychological phenomena (e.g., self-serving biases) can be explained
      in terms of active interpersonal inference. (3) Mentalizing naturally entails
      Bayesian updating of how people value social outcomes. Crucially this includes
      inference about one's own qualities and preferences. CONCLUSION: We inaugurate a
      Bayes optimal framework for modeling intersubject variability in mentalizing
      during interpersonal exchanges. Here, interpersonal representations are endowed
      with explicit functional and affective properties. We suggest the active
      inference framework lends itself to the study of psychiatric conditions where
      mentalizing is distorted.

PMID- 24723873
TI  - Unilateral deafness in children affects development of multi-modal modulation and
      default mode networks.
AB  - Monaural auditory input due to congenital or acquired unilateral hearing loss
      (UHL) may have neurobiological effects on the developing brain. Using functional
      magnetic resonance imaging (fMRI), we investigated the effect of UHL on the
      development of functional brain networks used for cross-modal processing.
      Children ages 7-12 with moderate or greater unilateral hearing loss of
      sensorineural origin (UHL-SN; N = 21) and normal-hearing controls (N = 23)
      performed an fMRI-compatible adaptation of the Token Test involving listening to
      a sentence such as "touched the small green circle and the large blue square" and
      simultaneously viewing an arrow touching colored shapes on a video. Children with
      right or severe-to-profound UHL-SN displayed smaller activation in a region
      encompassing the right inferior temporal, middle temporal, and middle occipital
      gyrus (BA 19/37/39), evidencing differences due to monaural hearing in cross
      modal modulation of the visual processing pathway. Children with UHL-SN displayed
      increased activation in the left posterior superior temporal gyrus, likely the
      result either of more effortful low-level processing of auditory stimuli or
      differences in cross-modal modulation of the auditory processing pathway.
      Additionally, children with UHL-SN displayed reduced deactivation of anterior and
      posterior regions of the default mode network. Results suggest that monaural
      hearing affects the development of brain networks related to cross-modal sensory
      processing and the regulation of the default network during processing of spoken
      language. 

PMID- 24723874
TI  - The effect of body posture on cognitive performance: a question of sleep quality.
AB  - Nearly all functional magnetic resonance imaging (fMRI) studies are conducted in
      the supine body posture, which has been discussed as a potential confounder of
      such examinations. The literature suggests that cognitive functions, such as
      problem solving or perception, differ between supine and upright postures.
      However, the effect of posture on many cognitive functions is still unknown.
      Therefore, the aim of the present study was to investigate the effects of body
      posture (supine vs. sitting) on one of the most frequently used paradigms in the
      cognitive sciences: the N-back working memory paradigm. Twenty-two subjects were
      investigated in a randomized within-subject design. Subjects performed the N-back
      task on two consecutive days in either the supine or the upright posture.
      Subjective sleep quality and chronic stress were recorded as covariates.
      Furthermore, changes in mood dimensions and heart rate variability (HRV) were
      assessed during the experiment. Results indicate that the quality of sleep
      strongly affects reaction times when subjects performed a working memory task in
      a supine posture. These effects, however, could not be observed in the sitting
      position. The findings can be explained by HRV parameters that indicated
      differences in autonomic regulation in the upright vs. the supine posture. The
      finding is of particular relevance for fMRI group comparisons when group
      differences in sleep quality cannot be ruled out. 

PMID- 24723875
TI  - Transcranial magnetic stimulation-induced global propagation of transient phase
      resetting associated with directional information flow.
AB  - Electroencephalogram (EEG) phase synchronization analyses can reveal large-scale
      communication between distant brain areas. However, it is not possible to
      identify the directional information flow between distant areas using
      conventional phase synchronization analyses. In the present study, we applied
      transcranial magnetic stimulation (TMS) to the occipital area in subjects who
      were resting with their eyes closed, and analyzed the spatial propagation of
      transient TMS-induced phase resetting by using the transfer entropy (TE), to
      quantify the causal and directional flow of information. The time-frequency EEG
      analysis indicated that the theta (5 Hz) phase locking factor (PLF) reached its
      highest value at the distant area (the motor area in this study), with a time lag
      that followed the peak of the transient PLF enhancements of the TMS-targeted area
      at the TMS onset. Phase-preservation index (PPI) analyses demonstrated
      significant phase resetting at the TMS-targeted area and distant area. Moreover,
      the TE from the TMS-targeted area to the distant area increased clearly during
      the delay that followed TMS onset. Interestingly, the time lags were almost
      coincident between the PLF and TE results (152 vs. 165 ms), which provides strong
      evidence that the emergence of the delayed PLF reflects the causal information
      flow. Such tendencies were observed only in the higher-intensity TMS condition,
      and not in the lower-intensity or sham TMS conditions. Thus, TMS may manipulate
      large-scale causal relationships between brain areas in an intensity-dependent
      manner. We demonstrated that single-pulse TMS modulated global phase dynamics and
      directional information flow among synchronized brain networks. Therefore, our
      results suggest that single-pulse TMS can manipulate both incoming and outgoing
      information in the TMS-targeted area associated with functional changes. 

PMID- 24723876
TI  - Localization of the epileptogenic foci in tuberous sclerosis complex: a pediatric
      case report.
AB  - Tuberous sclerosis complex (TSC) is a rare disorder of tissue growth and
      differentiation, characterized by benign hamartomas in the brain and other
      organs. Up to 90% of TSC patients develop epilepsy and 50% become medically
      intractable requiring resective surgery. The surgical outcome of TSC patients
      depends on the accurate identification of the epileptogenic zone consisting of
      tubers and the surrounding epileptogenic tissue. There is conflicting evidence
      whether the epileptogenic zone is in the tuber itself or in abnormally developed
      surrounding cortex. Here, we report the localization of the epileptiform activity
      among the many cortical tubers in a 4-year-old patient with TSC-related
      refractory epilepsy undergoing magnetoencephalography (MEG),
      electroencephalography (EEG), and diffusion tensor imaging (DTI). For MEG, we
      used a prototype system that offers higher spatial resolution and sensitivity
      compared to the conventional adult systems. The generators of interictal activity
      were localized using both EEG and MEG with equivalent current dipole (ECD) and
      minimum norm estimation (MNE) methods according to the current clinical
      standards. For DTI, we calculated four diffusion scalar parameters for the fibers
      passing through four ROIs defined: (i) at a large cortical tuber identified at
      the right quadrant, (ii) at the normal appearing tissue contralateral to the
      tuber, (iii) at the cluster formed by ECDs fitted at the peak of interictal
      spikes, and (iv) at the normal appearing tissue contralateral to the cluster.
      ECDs were consistently clustered at the vicinity of the large calcified cortical
      tuber. MNE and ECDs indicated epileptiform activity in the same areas. DTI
      analysis showed differences between the scalar values of the tracks passing
      through the tuber and the ECD cluster. In this illustrative case, we provide
      evidence from different neuroimaging modalities, which support the view that
      epileptiform activity may derive from abnormally developed tissue surrounding the
      tuber rather than the tuber itself. 

PMID- 24723877
TI  - Enhanced peripheral visual processing in congenitally deaf humans is supported by
      multiple brain regions, including primary auditory cortex.
AB  - Brain reorganization associated with altered sensory experience clarifies the
      critical role of neuroplasticity in development. An example is enhanced
      peripheral visual processing associated with congenital deafness, but the neural
      systems supporting this have not been fully characterized. A gap in our
      understanding of deafness-enhanced peripheral vision is the contribution of
      primary auditory cortex. Previous studies of auditory cortex that use anatomical
      normalization across participants were limited by inter-subject variability of
      Heschl's gyrus. In addition to reorganized auditory cortex (cross-modal
      plasticity), a second gap in our understanding is the contribution of altered
      modality-specific cortices (visual intramodal plasticity in this case), as well
      as supramodal and multisensory cortices, especially when target detection is
      required across contrasts. Here we address these gaps by comparing fMRI signal
      change for peripheral vs. perifoveal visual stimulation (11-15 degrees  vs. 2-7
      degrees ) in congenitally deaf and hearing participants in a blocked experimental
      design with two analytical approaches: a Heschl's gyrus region of interest
      analysis and a whole brain analysis. Our results using individually-defined
      primary auditory cortex (Heschl's gyrus) indicate that fMRI signal change for
      more peripheral stimuli was greater than perifoveal in deaf but not in hearing
      participants. Whole-brain analyses revealed differences between deaf and hearing
      participants for peripheral vs. perifoveal visual processing in extrastriate
      visual cortex including primary auditory cortex, MT+/V5, superior-temporal
      auditory, and multisensory and/or supramodal regions, such as posterior parietal
      cortex (PPC), frontal eye fields, anterior cingulate, and supplementary eye
      fields. Overall, these data demonstrate the contribution of neuroplasticity in
      multiple systems including primary auditory cortex, supramodal, and multisensory
      regions, to altered visual processing in congenitally deaf adults. 

PMID- 24723878
TI  - Improving the study of error monitoring with consideration of behavioral
      performance measures.

PMID- 24723880
TI  - Videogame interventions and spatial ability interactions.
AB  - Numerous research studies have been conducted on the use of videogames as tools
      to improve one's cognitive abilities. While meta-analyses and qualitative reviews
      have provided evidence that some aspects of cognition such as spatial imagery are
      modified after exposure to videogames, other evidence has shown that matrix
      reasoning measures of fluid intelligence do not show evidence of transfer from
      videogame training. In the current work, we investigate the available evidence
      for transfer specifically to nonverbal intelligence and spatial ability measures,
      given recent research that these abilities may be most sensitive to training on
      cognitive and working memory tasks. Accordingly, we highlight a few studies that
      on the surface provide evidence for transfer to spatial abilities, but a closer
      look at the pattern of data does not reveal a clean interpretation of the
      results. We discuss the implications of these results in relation to research
      design and statistical analysis practices. 

PMID- 24723879
TI  - A synthesis of evidence on inhibitory control and auditory hallucinations based
      on the Research Domain Criteria (RDoC) framework.
AB  - The National Institute of Mental Health initiative called the Research Domain
      Criteria (RDoC) project aims to provide a new approach to understanding mental
      illness grounded in the fundamental domains of human behavior and psychological
      functioning. To this end the RDoC framework encourages researchers and clinicians
      to think outside the [diagnostic] box, by studying symptoms, behaviors or
      biomarkers that cut across traditional mental illness categories. In this article
      we examine and discuss how the RDoC framework can improve our understanding of
      psychopathology by zeroing in on hallucinations- now widely recognized as a
      symptom that occurs in a range of clinical and non-clinical groups. We focus on a
      single domain of functioning-namely cognitive [inhibitory] control-and assimilate
      key findings structured around the basic RDoC "units of analysis," which span the
      range from observable behavior to molecular genetics. Our synthesis and critique
      of the literature provides a deeper understanding of the mechanisms involved in
      the emergence of auditory hallucinations, linked to the individual dynamics of
      inhibitory development before and after puberty; favors separate developmental
      trajectories for clinical and non-clinical hallucinations; yields new insights
      into co-occurring emotional and behavioral problems; and suggests some novel
      avenues for treatment. 

PMID- 24723881
TI  - Optimal attentional modulation of a neural population.
AB  - Top-down attention has often been separately studied in the contexts of either
      optimal population coding or biasing of visual search. Yet, both are intimately
      linked, as they entail optimally modulating sensory variables in neural
      populations according to top-down goals. Designing experiments to probe top-down
      attentional modulation is difficult because non-linear population dynamics are
      hard to predict in the absence of a concise theoretical framework. Here, we
      describe a unified framework that encompasses both contexts. Our work sheds light
      onto the ongoing debate on whether attention modulates neural response gain,
      tuning width, and/or preferred feature. We evaluate the framework by conducting
      simulations for two tasks: (1) classification (discrimination) of two stimuli s a
      and s b and (2) searching for a target T among distractors D. Results demonstrate
      that all of gain, tuning, and preferred feature modulation happen to different
      extents, depending on stimulus conditions and task demands. The theoretical
      analysis shows that task difficulty (linked to difference Delta between s a and s
      b , or T, and D) is a crucial factor in optimal modulation, with different
      effects in discrimination vs. search. Further, our framework allows us to
      quantify the relative utility of neural parameters. In easy tasks (when Delta is
      large compared to the density of the neural population), modulating gains and
      preferred features is sufficient to yield nearly optimal performance; however, in
      difficult tasks (smaller Delta), modulating tuning width becomes necessary to
      improve performance. This suggests that the conflicting reports from different
      experimental studies may be due to differences in tasks and in their
      difficulties. We further propose future electrophysiology experiments to observe
      different types of attentional modulation in a same neuron. 

PMID- 24723882
TI  - A web-portal for interactive data exploration, visualization, and hypothesis
      testing.
AB  - Clinical research studies generate data that need to be shared and statistically
      analyzed by their participating institutions. The distributed nature of research
      and the different domains involved present major challenges to data sharing,
      exploration, and visualization. The Data Portal infrastructure was developed to
      support ongoing research in the areas of neurocognition, imaging, and genetics.
      Researchers benefit from the integration of data sources across domains, the
      explicit representation of knowledge from domain experts, and user interfaces
      providing convenient access to project specific data resources and algorithms.
      The system provides an interactive approach to statistical analysis, data mining,
      and hypothesis testing over the lifetime of a study and fulfills a mandate of
      public sharing by integrating data sharing into a system built for active data
      exploration. The web-based platform removes barriers for research and supports
      the ongoing exploration of data. 

PMID- 24723884
TI  - Time changes with feeling of speed: an embodied perspective.
AB  - The speed of moving stimuli can bias duration perception. Here, we investigated
      whether words describing different speeds influence subjective duration
      estimation in a temporal bisection task. Duration estimations of two different
      types of speed words (fast- vs. slow-speed words) were compared. We found that
      the time bisection point was significantly lower for fast-speed words than for
      slow-speed words, suggesting that the durations of fast-speed words were
      overestimated compared to the slow-speed words. In contrast, fast- and slow-speed
      words did not significantly differ in just noticeable differences and Weber
      fractions, indicating that the types of speed words did not influence the
      sensitivity of duration estimation. These results provide new evidence to support
      the theory of embodied cognition in the context of implicit meaning of a speed
      word. 

PMID- 24723885
TI  - A Chinese Chan-based lifestyle intervention improves memory of older adults.
AB  - This study aims to explore the potential benefits of a Chinese Chan-based
      lifestyle intervention on enhancing memory in older people with lower memory
      function. Forty-four aged 60-83 adults with various level of memory ability
      participated in the study. Their memories (including verbal and visual
      components) were assessed before and after 3 months intervention. The
      intervention consisted of 12 sessions, with one 90 min session per week. The
      intervention involved components of adopting a special vegetarian diet,
      practicing a type of mind-body exercises, and learning self-realization. Elderly
      with lower memory function at the baseline (i.e., their performance on
      standardized memory tests was within 25th percentile) showed a significant memory
      improvement after the intervention. Their verbal and visual memory performance
      has showed 50 and 49% enhancement, respectively. In addition, their improvement
      can be considered as a reliable and clinically significant change as reflected by
      their significant pre-post differences and reliable change indices. Such robust
      treatment effect was found to be specific to memory functions, but less
      influencing on the other cognitive functions. These preliminary encouraging
      results have shed some light on the potential applicability of the Chinese Chan
      based lifestyle intervention as a method for enhancing memory in the elderly
      population. 

PMID- 24723883
TI  - A review of multivariate analyses in imaging genetics.
AB  - Recent advances in neuroimaging technology and molecular genetics provide the
      unique opportunity to investigate genetic influence on the variation of brain
      attributes. Since the year 2000, when the initial publication on brain imaging
      and genetics was released, imaging genetics has been a rapidly growing research
      approach with increasing publications every year. Several reviews have been
      offered to the research community focusing on various study designs. In addition
      to study design, analytic tools and their proper implementation are also critical
      to the success of a study. In this review, we survey recent publications using
      data from neuroimaging and genetics, focusing on methods capturing multivariate
      effects accommodating the large number of variables from both imaging data and
      genetic data. We group the analyses of genetic or genomic data into either a
      priori driven or data driven approach, including gene-set enrichment analysis,
      multifactor dimensionality reduction, principal component analysis, independent
      component analysis (ICA), and clustering. For the analyses of imaging data, ICA
      and extensions of ICA are the most widely used multivariate methods. Given
      detailed reviews of multivariate analyses of imaging data available elsewhere, we
      provide a brief summary here that includes a recently proposed method known as
      independent vector analysis. Finally, we review methods focused on bridging the
      imaging and genetic data by establishing multivariate and multiple genotype
      phenotype-associations, including sparse partial least squares, sparse canonical
      correlation analysis, sparse reduced rank regression and parallel ICA. These
      methods are designed to extract latent variables from both genetic and imaging
      data, which become new genotypes and phenotypes, and the links between the new
      genotype-phenotype pairs are maximized using different cost functions. The
      relationship between these methods along with their assumptions, advantages, and
      limitations are discussed. 

PMID- 24723886
TI  - The effects of automated artifact removal algorithms on electroencephalography
      based Alzheimer's disease diagnosis.
AB  - Over the last decade, electroencephalography (EEG) has emerged as a reliable tool
      for the diagnosis of cortical disorders such as Alzheimer's disease (AD). EEG
      signals, however, are susceptible to several artifacts, such as ocular, muscular,
      movement, and environmental. To overcome this limitation, existing diagnostic
      systems commonly depend on experienced clinicians to manually select artifact
      free epochs from the collected multi-channel EEG data. Manual selection, however,
      is a tedious and time-consuming process, rendering the diagnostic system "semi
      automated." Notwithstanding, a number of EEG artifact removal algorithms have
      been proposed in the literature. The (dis)advantages of using such algorithms in
      automated AD diagnostic systems, however, have not been documented; this paper
      aims to fill this gap. Here, we investigate the effects of three state-of-the-art
      automated artifact removal (AAR) algorithms (both alone and in combination with
      each other) on AD diagnostic systems based on four different classes of EEG
      features, namely, spectral, amplitude modulation rate of change, coherence, and
      phase. The three AAR algorithms tested are statistical artifact rejection (SAR),
      blind source separation based on second order blind identification and canonical
      correlation analysis (BSS-SOBI-CCA), and wavelet enhanced independent component
      analysis (wICA). Experimental results based on 20-channel resting-awake EEG data
      collected from 59 participants (20 patients with mild AD, 15 with moderate-to
      severe AD, and 24 age-matched healthy controls) showed the wICA algorithm alone
      outperforming other enhancement algorithm combinations across three tasks:
      diagnosis (control vs. mild vs. moderate), early detection (control vs. mild),
      and disease progression (mild vs. moderate), thus opening the doors for fully
      automated systems that can assist clinicians with early detection of AD, as well
      as disease severity progression assessment. 

PMID- 24723888
TI  - Who is the scientist in bio-medical research, the author or the reviewer?

PMID- 24723887
TI  - Endothelial heterogeneity in the umbilico-placental unit: DNA methylation as an
      innuendo of epigenetic diversity.
AB  - The endothelium is a multifunctional heterogeneous tissue playing a key role in
      the physiology of every organ. To accomplish this role the endothelium presents a
      phenotypic diversity that is early prompted during vascular development, allowing
      it to cope with specific requirements in a time- and site-specific manner. During
      the last decade several reports show that endothelial diversity is also present
      in the umbilico-placental vasculature, with differences between macro- and
      microvascular vessels as well as arterial and venous endothelium. This diversity
      is evidenced in vitro as a higher angiogenic capacity in the microcirculation; or
      disparity in the levels of several molecules that control endothelial function
      (i.e., receptor for growth factors, vasoactive mediators, and adhesion molecules)
      which frequently are differentially expressed between arterial and venous
      endothelium. Emerging evidence suggests that endothelial diversity would be
      prominently driven by epigenetic mechanisms which also control the basal
      expression of endothelial-specific genes. This review outlines evidence for
      endothelial diversity since early stages of vascular development and how this
      heterogeneity is expressed in the umbilico-placental vasculature. Furthermore a
      brief picture of epigenetic mechanisms and their role on endothelial physiology
      emphasizing new data on umbilical and placental endothelial cells is presented.
      Unraveling the role of epigenetic mechanisms on long term endothelial physiology
      and its functional diversity would contribute to develop more accurate
      therapeutic interventions. Altogether these data show that micro- versus macro
      vascular, or artery versus vein comparisons are an oversimplification of the
      complexity occurring in the endothelium at different levels, and the necessity
      for the future research to establish the precise source of cells which are under
      study. 

PMID- 24723889
TI  - Label-free drug discovery.
AB  - Current drug discovery is dominated by label-dependent molecular approaches,
      which screen drugs in the context of a predefined and target-based hypothesis in
      vitro. Given that target-based discovery has not transformed the industry,
      phenotypic screen that identifies drugs based on a specific phenotype of cells,
      tissues, or animals has gained renewed interest. However, owing to the intrinsic
      complexity in drug-target interactions, there is often a significant gap between
      the phenotype screened and the ultimate molecular mechanism of action sought.
      This paper presents a label-free strategy for early drug discovery. This strategy
      combines label-free cell phenotypic profiling with computational approaches, and
      holds promise to bridge the gap by offering a kinetic and holistic representation
      of the functional consequences of drugs in disease relevant cells that is
      amenable to mechanistic deconvolution. 

PMID- 24723890
TI  - Is "capacitive coupling" purely excitatory in the cardiac tissue?

PMID- 24723891
TI  - Mindfulness may both moderate and mediate the effect of physical fitness on
      cardiovascular responses to stress: a speculative hypothesis.
AB  - The psychological construct of mindfulness refers to an awareness that emerges by
      intentionally paying attention to the present experience in a non-judgmental or
      evaluative way. This particular quality of awareness has been associated to
      several indicators of physical and psychological health, and can be developed
      using mindfulness-based interventions (MBIs), and therefore MBIs have been
      successfully applied as preventive and complementary interventions and therapies
      in medicine and psychology. Together with quiet sitting and lying meditation
      practices, mindful physical exercises such as "mindful walking" and "mindful
      movement" are key elements in MBIs and couple muscular activity with an
      internally directed focus, improving interoceptive attention to bodily
      sensations. In addition, MBIs seem to share similar mechanisms with physical
      fitness (PF) by which they may influence cardiovascular responses to stress.
      Based on these facts, it is feasible to raise the question of whether physical
      training itself may induce the development of that particular quality of
      awareness associated with mindfulness, or if one's dispositional mindfulness (DM)
      (the tendency to be more mindful in daily life) could moderate the effects of
      exercise on cardiovascular response to stress. The role of mindfulness as a
      mediator or moderator of the effect of exercise training on cardiovascular
      responses to stress has barely been studied. In this study, we have hypothesized
      pathways (moderation and mediation) by which mindfulness could significantly
      influence the effects of PF on cardiovascular responses to stress and discussed
      potential practical ways to test these hypotheses. 

PMID- 24723892
TI  - Building a brain under nutritional restriction: insights on sparing and
      plasticity from Drosophila studies.
AB  - While the growth of the developing brain is known to be well-protected compared
      to other organs in the face of nutrient restriction (NR), careful analysis has
      revealed a range of structural alterations and long-term neurological defects.
      Yet, despite intensive studies, little is known about the basic principles that
      govern brain development under nutrient deprivation. For over 20 years,
      Drosophila has proved to be a useful model for investigating how a functional
      nervous system develops from a restricted number of neural stem cells (NSCs).
      Recently, a few studies have started to uncover molecular mechanisms as well as
      region-specific adaptive strategies that preserve brain functionality and
      neuronal repertoire under NR, while modulating neuron numbers. Here, we review
      the developmental constraints that condition the response of the developing brain
      to NR. We then analyze the recent Drosophila work to highlight key principles
      that drive sparing and plasticity in different regions of the central nervous
      system (CNS). As simple animal models start to build a more integrated picture,
      understanding how the developing brain copes with NR could help in defining
      strategies to limit damage and improve brain recovery after birth. 

PMID- 24723893
TI  - Measuring brain temperature without a thermometer.

PMID- 24723895
TI  - Alcohol Use is Not Directly Related to the Perceived Control of Depressive
      Symptoms in Patients with Depressive Symptoms.
AB  - Treatment-seeking patients (N = 233) were recruited as they started a course of
      relapse prevention and coping with depression. The mean Beck depression inventory
      (BDI-II) score was 26 points, indicating a moderate degree of depression. The
      sample was recruited from different outpatient clinics and screened for alcohol
      related problems with the alcohol use disorders identification test (AUDIT).
      Almost half of the total sample had a score on AUDIT >8 indicating an alcohol
      problem. The participants in this study did not undergo a clinical interview to
      check out if their symptoms, as assessed with BDI-II and AUDIT, were part of a
      formal diagnosis in accordance with the criteria in ICD 10 or DSM IV. A specific
      instrument, perceived uncontrollability of depression (UNCONTROL), was used to
      measure the persons' perceived control of depressive symptoms; a set of
      statements about coping with depressive symptoms where high scores indicate lack
      of coping with the symptoms. Alcohol problems were not found to be significantly
      associated with the perceived control of ongoing depressive symptoms and did not
      moderate the relationship between depressive symptoms and the perceived control
      of depressive symptoms. The results question the assumption that alcohol use is
      related to coping with depressive symptoms in patients with alcohol abuse and
      depressive symptoms. 

PMID- 24723896
TI  - Interword and intraword pause threshold in writing.
AB  - Writing words in real life involves setting objectives, imagining a recipient,
      translating ideas into linguistic forms, managing grapho-motor gestures, etc.
      Understanding writing requires observation of the processes as they occur in real
      time. Analysis of pauses is one of the preferred methods for accessing the
      dynamics of writing and is based on the idea that pauses are behavioral
      correlates of cognitive processes. However, there is a need to clarify what we
      are observing when studying pause phenomena, as we will argue in the first
      section. This taken into account, the study of pause phenomena can be considered
      following two approaches. A first approach, driven by temporality, would define a
      threshold and observe where pauses, e.g., scriptural inactivity occurs. A second
      approach, linguistically driven, would define structural units and look for
      scriptural inactivity at the boundaries of these units or within these units.
      Taking a temporally driven approach, we present two methods which aim at the
      automatic identification of scriptural inactivity which is most likely not
      attributable to grapho-motor management in texts written by children and
      adolescents using digitizing tablets in association with Eye and Pen ((c))
      (Chesnet and Alamargot, 2005). The first method is purely statistical and is
      based on the idea that the distribution of pauses exhibits different Gaussian
      components each of them corresponding to a different type of pause. After having
      reviewed the limits of this statistical method, we present a second method based
      on writing dynamics which attempts to identify breaking points in the writing
      dynamics rather than relying only on pause duration. This second method needs to
      be refined to overcome the fact that calculation is impossible when there is
      insufficient data which is often the case when working with young scriptors. 

PMID- 24723894
TI  - Computational neuropsychiatry - schizophrenia as a cognitive brain network
      disorder.
AB  - Computational modeling of functional brain networks in fMRI data has advanced the
      understanding of higher cognitive function. It is hypothesized that functional
      networks mediating higher cognitive processes are disrupted in people with
      schizophrenia. In this article, we review studies that applied measures of
      functional and effective connectivity to fMRI data during cognitive tasks, in
      particular working memory fMRI studies. We provide a conceptual summary of the
      main findings in fMRI data and their relationship with neurotransmitter systems,
      which are known to be altered in individuals with schizophrenia. We consider
      possible developments in computational neuropsychiatry, which are likely to
      further our understanding of how key functional networks are altered in
      schizophrenia. 

PMID- 24723897
TI  - Irrelevant stimulus processing in ADHD: catecholamine dynamics and attentional
      networks.
AB  - A cardinal symptom of attention deficit and hyperactivity disorder (ADHD) is a
      general distractibility where children and adults shift their attentional focus
      to stimuli that are irrelevant to the ongoing behavior. This has been attributed
      to a deficit in dopaminergic signaling in cortico-striatal networks that regulate
      goal-directed behavior. Furthermore, recent imaging evidence points to an
      impairment of large scale, antagonistic brain networks that normally contribute
      to attentional engagement and disengagement, such as the task-positive networks
      and the default mode network (DMN). Related networks are the ventral attentional
      network (VAN) involved in attentional shifting, and the salience network (SN)
      related to task expectancy. Here we discuss the tonic-phasic dynamics of
      catecholaminergic signaling in the brain, and attempt to provide a link between
      this and the activities of the large-scale cortical networks that regulate
      behavior. More specifically, we propose that a disbalance of tonic catecholamine
      levels during task performance produces an emphasis of phasic signaling and
      increased excitability of the VAN, yielding distractibility symptoms. Likewise,
      immaturity of the SN may relate to abnormal tonic signaling and an incapacity to
      build up a proper executive system during task performance. We discuss different
      lines of evidence including pharmacology, brain imaging and electrophysiology,
      that are consistent with our proposal. Finally, restoring the pharmacodynamics of
      catecholaminergic signaling seems crucial to alleviate ADHD symptoms; however,
      the possibility is open to explore cognitive rehabilitation strategies to top
      down modulate network dynamics compensating the pharmacological deficits. 

PMID- 24723899
TI  - Attention to advertising and memory for brands under alcohol intoxication.
AB  - In an attempt to discover new possibilities for advertising in uncluttered
      environments marketers have recently begun using ambient advertising in, for
      instance, bars and pubs. However, advertising in such licensed premises have to
      deal with the fact that many consumers are under the influence of alcohol while
      viewing the ad. This paper examines the effect of alcohol intoxication on
      attention to and memory for advertisements in two experiments. Study 1 used a
      forced exposure manipulation and revealed increased attention to logos under
      alcohol intoxication consistent with the psychopharmacological prediction that
      alcohol intoxication narrows attention to the more salient features in the visual
      environment. Study 2 used a voluntary exposure manipulation in which ads were
      embedded in a magazine. The experiment revealed that alcohol intoxication reduces
      voluntary attention to ads and leads to a significant reduction in memory for the
      viewed ads. In popular terms consuming one or two beers reduces brand recall from
      40 to 36% while being heavily intoxicated further reduces brand recall to 17%. 

PMID- 24723898
TI  - Functional and structural comparison of visual lateralization in birds - similar
      but still different.
AB  - Vertebrate brains display physiological and anatomical left-right differences,
      which are related to hemispheric dominances for specific functions. Functional
      lateralizations likely rely on structural left-right differences in intra- and
      interhemispheric connectivity patterns that develop in tight gene-environment
      interactions. The visual systems of chickens and pigeons show that asymmetrical
      light stimulation during ontogeny induces a dominance of the left hemisphere for
      visuomotor control that is paralleled by projection asymmetries within the
      ascending visual pathways. But structural asymmetries vary essentially between
      both species concerning the affected pathway (thalamo- vs. tectofugal system),
      constancy of effects (transient vs. permanent), and the hemisphere receiving
      stronger bilateral input (right vs. left). These discrepancies suggest that at
      least two aspects of visual processes are influenced by asymmetric light
      stimulation: (1) visuomotor dominance develops within the ontogenetically
      stronger stimulated hemisphere but not necessarily in the one receiving stronger
      bottom-up input. As a secondary consequence of asymmetrical light experience,
      lateralized top-down mechanisms play a critical role in the emergence of
      hemispheric dominance. (2) Ontogenetic light experiences may affect the dominant
      use of left- and right-hemispheric strategies. Evidences from social and spatial
      cognition tasks indicate that chickens rely more on a right-hemispheric global
      strategy whereas pigeons display a dominance of the left hemisphere. Thus,
      behavioral asymmetries are linked to a stronger bilateral input to the right
      hemisphere in chickens but to the left one in pigeons. The degree of bilateral
      visual input may determine the dominant visual processing strategy when redundant
      encoding is possible. This analysis supports that environmental stimulation
      affects the balance between hemispheric-specific processing by lateralized
      interactions of bottom-up and top-down systems. 

PMID- 24723900
TI  - The illusion confusion.
AB  - In Batty (2010b), I argue that there are no olfactory illusions. Central to the
      traditional notions of illusion and hallucination is a notion of object-failure
      the failure of an experience to represent particular objects. Because there are
      no presented objects in the case of olfactory experience, I argue that the
      traditional ways of categorizing non-veridical experience do not apply to the
      olfactory case. In their place, I propose a novel notion of non-veridical
      experience for the olfactory case. In his (2011), Stevenson responds to my claim
      that there are no olfactory illusions. Although he agrees that it is natural-or
      at least commonplace-to think there are no olfactory illusions, he argues that
      there are and provides examples of them, many of which he suggests have analogs
      in the visual and auditory domains. In this paper, I examine the nature of the
      disagreement between us. I argue that Stevenson fails to argue against my
      conclusion that there are no olfactory illusions. 

PMID- 24723901
TI  - Meal replacement: calming the hot-state brain network of appetite.
AB  - There is a growing awareness in the field of neuroscience that the self
      regulation of eating behavior is driven by complex networks within the brain.
      These networks may be vulnerable to "hot states" which people can move into and
      out of dynamically throughout the course of a day as a function of changes in
      affect or visceral cues. The goal of the current study was to identify and
      determine differences in the Hot-state Brain Network of Appetite (HBN-A) that
      exists after a brief period of food restraint followed either by the consumption
      of a meal replacement (MR) or water. Fourteen overweight/obese adults came to our
      laboratory on two different occasions. Both times they consumed a controlled
      breakfast meal and then were restricted from eating for 2.5 h prior to an MRI
      scan. On one visit, they consumed a meal replacement (MR) liquid meal after this
      period of food restriction; on the other visit they consumed an equal amount of
      water. After these manipulations, the participants underwent a resting fMRI scan.
      Our first study aim employed an exploratory, data-driven approach to identify
      hubs relevant to the HBN-A. Using data from the water condition, five regions
      were found to be the hubs or nodes of the HBN-A: insula, anterior cingulated
      cortex, the superior temporal pole, the amygdala, and the hippocampus. We then
      demonstrated that the consumption of a liquid MR dampened interconnectivity
      between the nodes of the HBN-A as compared to water. Importantly and consistent
      with these network data, the consumption of a MR beverage also lowered state
      cravings and hunger. 

PMID- 24723902
TI  - Ostensive signals support learning from novel attention cues during infancy.
AB  - Social attention cues (e.g., head turning, gaze direction) highlight which events
      young infants should attend to in a busy environment and, recently, have been
      shown to shape infants' likelihood of learning about objects and events. Although
      studies have documented which social cues guide attention and learning during
      early infancy, few have investigated how infants learn to learn from attention
      cues. Ostensive signals, such as a face addressing the infant, often precede
      social attention cues. Therefore, it is possible that infants can use ostensive
      signals to learn from other novel attention cues. In this training study, 8-month
      olds were cued to the location of an event by a novel non-social attention cue
      (i.e., flashing square) that was preceded by an ostensive signal (i.e., a face
      addressing the infant). At test, infants predicted the appearance of specific
      multimodal events cued by the flashing squares, which were previously shown to
      guide attention to but not inform specific predictions about the multimodal
      events (Wu and Kirkham, 2010). Importantly, during the generalization phase, the
      attention cue continued to guide learning of these events in the absence of the
      ostensive signal. Subsequent experiments showed that learning was less successful
      when the ostensive signal was absent even if an interesting but non-ostensive
      social stimulus preceded the same cued events. 

PMID- 24723903
TI  - Switching between global and local levels: the level repetition effect and its
      hemispheric asymmetry.
AB  - The global level of hierarchical stimuli (Navon's stimuli) is typically processed
      quicker and better than the local level; further differential hemispheric
      dominance is described for local (left hemisphere, LH) and global (right
      hemisphere, RH) processing. However, neuroimaging and behavioral data indicate
      that stimulus category (letter or object) could modulate the hemispheric
      asymmetry for the local level processing. Besides, when the targets are
      unpredictably displayed at the global or local level, the participant has to
      switch between levels, and the magnitude of the switch cost increases with the
      number of repeated-level trials preceding the switch. The hemispheric asymmetries
      associated with level switching is an unresolved issue. LH areas may be involved
      in carrying over the target level information in case of level repetition. These
      areas may also largely participate in the processing of level-changed trials.
      Here we hypothesized that RH areas underly the inhibitory mechanism performed on
      the irrelevant level, as one of the components of the level switching process. In
      an experiment using a within-subject design, hierarchical stimuli were briefly
      presented either to the right or to the left visual field. 32 adults were
      instructed to identify the target at the global or local level. We assessed a
      possible RH dominance for the non-target level inhibition by varying the
      attentional demands through the manipulation of level repetitions (two or gour
      repeated-level trials before the switch). The behavioral data confirmed a LH
      specialization only for the local level processing of letter-based stimuli, and
      detrimental effect of increased level repetitions before a switch. Further, data
      provides evidence for a RH advantage in inhibiting the non-target level. Taken
      together, the data supports the notion of the existence of multiple mechanisms
      underlying level-switch effects. 

PMID- 24723904
TI  - Interpersonal style should be included in taxonomies of behavior change
      techniques.

PMID- 24723905
TI  - Deception research today.

PMID- 24723906
TI  - Three-year-olds' theories of mind in actions and words.
AB  - Understanding observable behavior by considering mental representations is
      central to social cognition. Research reveals quite different developmental
      trajectories for this ability depending on whether tasks assess implicit or
      explicit theory of mind (ToM). Yet, how to define implicit vs. explicit ToM, the
      tasks that elicit each, and the types of behavior that each can support, have
      remained unclear. The present study (n = 47) found that 3-year-olds incorporate
      predictions based on false beliefs into their intentional actions, but not -
      following identical scenarios - into their verbal responses. These data show that
      implicit ToM supports a broader range of behaviors than previously indicated and
      further illustrates the entrenched nature of the distinction between implicit and
      explicit knowledge in early conceptual development. 

PMID- 24723907
TI  - Distraction during learning with hypermedia: difficult tasks help to keep task
      goals on track.
AB  - In educational hypermedia environments, students are often confronted with
      potential sources of distraction arising from additional information that, albeit
      interesting, is unrelated to their current task goal. The paper investigates the
      conditions under which distraction occurs and hampers performance. Based on
      theories of volitional action control it was hypothesized that interesting
      information, especially if related to a pending goal, would interfere with task
      performance only when working on easy, but not on difficult tasks. In Experiment
      1, 66 students learned about probability theory using worked examples and solved
      corresponding test problems, whose task difficulty was manipulated. As a second
      factor, the presence of interesting information unrelated to the primary task was
      varied. Results showed that students solved more easy than difficult probability
      problems correctly. However, the presence of interesting, but task-irrelevant
      information did not interfere with performance. In Experiment 2, 68 students
      again engaged in example-based learning and problem solving in the presence of
      task-irrelevant information. Problem-solving difficulty was varied as a first
      factor. Additionally, the presence of a pending goal related to the task
      irrelevant information was manipulated. As expected, problem-solving performance
      declined when a pending goal was present during working on easy problems, whereas
      no interference was observed for difficult problems. Moreover, the presence of a
      pending goal reduced the time on task-relevant information and increased the time
      on task-irrelevant information while working on easy tasks. However, as revealed
      by mediation analyses these changes in overt information processing behavior did
      not explain the decline in problem-solving performance. As an alternative
      explanation it is suggested that goal conflicts resulting from pending goals
      claim cognitive resources, which are then no longer available for learning and
      problem solving. 

PMID- 24723908
TI  - Wake-up stroke: clinical characteristics, imaging findings, and treatment option 
      an update.
AB  - About 25% of all strokes occur during sleep, i.e., without knowledge of exact
      time of symptom onset. According to licensing criteria, this large group of
      patients is excluded from treatment with received tissue-plasminogen activator,
      the only specific stroke treatment proven effective in large randomized trials.
      This paper reviews clinical and imaging characteristics of wake-up stroke and
      gives an update on treatment options for these patients. From clinical and
      imaging studies, there is evidence suggesting that many wake-up strokes occur
      close to awakening and thus, patients might be within the approved time-window of
      thrombolysis when presenting to the emergency department. Several imaging
      approaches are suggested to identify wake-up stroke patients likely to benefit
      from thrombolysis, including non-contrast CT, CT-perfusion, penumbral MRI, and
      the recent concept of diffusion weighted imaging-fluid attenuated inversion
      recovery (DWI-FLAIR). A number of small case series and observational studies
      report results of thrombolysis in wake-up stroke, and no safety concerns have
      occurred, while conclusions on efficacy cannot be drawn from these studies. To
      this end, there are ongoing clinical trials enrolling wake-up stroke patients
      based on imaging findings, i.e., the DWI-FLAIR-mismatch (WAKE-UP) or penumbral
      imaging (EXTEND). The results of these trials will provide evidence to guide
      thrombolysis in wake-up stroke and thus, expand treatment options for this large
      group of stroke patients. 

PMID- 24723909
TI  - The Relationship between Subnormal Peak-Stimulated Growth Hormone Levels and
      Auxological Characteristics in Obese Children.
AB  - CONTEXT: The hypothesis that obese children are overdiagnosed with growth hormone
      deficiency (GHD) has not been adequately investigated in the context of adiposity
      related differences in auxology. AIM: To investigate the differences in
      auxological parameters between short, prepubertal, obese children, and normal
      weight peers who underwent growth hormone stimulation testing (GHST). HYPOTHESIS:
      Over-weight/obese children with GHD [peak growth hormone (GH) < 10 MUg/L] will
      have higher values for growth velocity (GV) standard deviation score (SDS), bone
      age minus chronological age (BA - CA), and child height SDS minus mid-parental
      height (MPTH) SDS when compared to normal-weight GHD peers. SUBJECTS AND METHODS:
      A retrospective review of anthropometric and provocative GHST data of 67
      prepubertal, GH-naive children of age 10.21 +/- 2.56 years (male n = 45, age 10.8
      +/- 2.60 years; female n = 22, age 8.94 +/- 2.10). INCLUSION CRITERIA: GHST using
      arginine and clonidine. EXCLUSION CRITERIA: hypopituitarism, abnormal pituitary
      magnetic resonance imaging scan, syndromic obesity, or syndromic short stature.
      Data were expressed as mean +/- SD. RESULTS: The over-weight/obese children with
      peak GH of <10 MUg/L had significantly lower value for natural log (ln) peak GH
      (1.45 +/- 0.09 vs. 1.83 +/- 0.35, p = 0.022), but similar values for GV SDS,
      insulin-like growth factor-I, insulin-like growth factor binding protein-3, bone
      age, BA - CA, MPTH, and child height SDS minus MPTH SDS compared to normal-weight
      peers with GHD. After adjusting for covariates, the over-weight/obese children
      (BMI >= 85th percentile) were >7 times more likely than normal-weight subjects
      (BMI < 85th percentile) to have a peak GH of <10 MUg/L, and 23 times more likely
      to have a peak GH of <7 MUg/L (OR = 23.3, p = 0.021). There was a significant
      inverse relationships between BMI SDS and the ln of peak GH (beta = -0.40, r (2)
      = 0.26, p = 0.001), but not for BMI SDS vs. GV SDS, ln peak GH vs. BA, or ln peak
      GH vs. GV SDS. CONCLUSION: Subnormal peak GH levels in obese prepubertal children
      are not associated with unique pre-GHST auxological characteristics.

PMID- 24723912
TI  - Bacterial computing: a form of natural computing and its applications.
AB  - The capability to establish adaptive relationships with the environment is an
      essential characteristic of living cells. Both bacterial computing and bacterial
      intelligence are two general traits manifested along adaptive behaviors that
      respond to surrounding environmental conditions. These two traits have generated
      a variety of theoretical and applied approaches. Since the different systems of
      bacterial signaling and the different ways of genetic change are better known and
      more carefully explored, the whole adaptive possibilities of bacteria may be
      studied under new angles. For instance, there appear instances of molecular
      "learning" along the mechanisms of evolution. More in concrete, and looking
      specifically at the time dimension, the bacterial mechanisms of learning and
      evolution appear as two different and related mechanisms for adaptation to the
      environment; in somatic time the former and in evolutionary time the latter. In
      the present chapter it will be reviewed the possible application of both kinds of
      mechanisms to prokaryotic molecular computing schemes as well as to the solution
      of real world problems. 

PMID- 24723913
TI  - The microbial nitrogen cycling potential is impacted by polyaromatic hydrocarbon
      pollution of marine sediments.
AB  - During hydrocarbon exposure, the composition and functional dynamics of marine
      microbial communities are altered, favoring bacteria that can utilize this rich
      carbon source. Initial exposure of high levels of hydrocarbons in aerobic surface
      sediments can enrich growth of heterotrophic microorganisms having hydrocarbon
      degradation capacity. As a result, there can be a localized reduction in oxygen
      potential within the surface layer of marine sediments causing anaerobic zones.
      We hypothesized that increasing exposure to elevated hydrocarbon concentrations
      would positively correlate with an increase in denitrification processes and the
      net accumulation of dinitrogen. This hypothesis was tested by comparing the
      relative abundance of genes associated with nitrogen metabolism and nitrogen
      cycling identified in 6 metagenomes from sediments contaminated by polyaromatic
      hydrocarbons from the Deepwater Horizon (DWH) oil spill in the Gulf of Mexico,
      and 3 metagenomes from sediments associated with natural oil seeps in the Santa
      Barbara Channel. An additional 8 metagenomes from uncontaminated sediments from
      the Gulf of Mexico were analyzed for comparison. We predicted relative changes in
      metabolite turnover as a function of the differential microbial gene abundances,
      which showed predicted accumulation of metabolites associated with
      denitrification processes, including anammox, in the contaminated samples
      compared to uncontaminated sediments, with the magnitude of this change being
      positively correlated to the hydrocarbon concentration and exposure duration.
      These data highlight the potential impact of hydrocarbon inputs on N cycling
      processes in marine sediments and provide information relevant for system scale
      models of nitrogen metabolism in affected ecosystems. 

PMID- 24723914
TI  - Helicobacter pylori DNA methyltransferases and the epigenetic field effect in
      cancerization.

PMID- 24723911
TI  - Mechanisms of therapeutic resistance in cancer (stem) cells with emphasis on
      thyroid cancer cells.
AB  - The two main reasons for death of cancer patients, tumor recurrence and
      metastasis, are multi-stage cellular processes that involve increased cell
      plasticity and coincide with elevated resistance to anti-cancer treatments.
      Epithelial-to-mesenchymal transition (EMT) is a key contributor to metastasis in
      many cancer types, including thyroid cancer and is known to confer stem cell-like
      properties onto cancer cells. This review provides an overview of molecular
      mechanisms and factors known to contribute to cancer cell plasticity and capable
      of enhancing cancer cell resistance to radio- and chemotherapy. We elucidate the
      role of DNA repair mechanisms in contributing to therapeutic resistance, with a
      special emphasis on thyroid cancer. Next, we explore the emerging roles of
      autophagy and damage-associated molecular pattern responses in EMT and
      chemoresistance in tumor cells. Finally, we demonstrate how cancer cells,
      including thyroid cancer cells, can highjack the oncofetal nucleoprotein high
      mobility group A2 to gain increased transformative cell plasticity, prevent
      apoptosis, and enhance metastasis of chemoresistant tumor cells. 

PMID- 24723910
TI  - Central pathways integrating metabolism and reproduction in teleosts.
AB  - Energy balance plays an important role in the control of reproduction. However,
      the cellular and molecular mechanisms connecting the two systems are not well
      understood especially in teleosts. The hypothalamus plays a crucial role in the
      regulation of both energy balance and reproduction, and contains a number of
      neuropeptides, including gonadotropin-releasing hormone (GnRH), orexin,
      neuropeptide-Y, ghrelin, pituitary adenylate cyclase-activating polypeptide,
      alpha-melanocyte stimulating hormone, melanin-concentrating hormone,
      cholecystokinin, 26RFamide, nesfatin, kisspeptin, and gonadotropin-inhibitory
      hormone. These neuropeptides are involved in the control of energy balance and
      reproduction either directly or indirectly. On the other hand, synthesis and
      release of these hypothalamic neuropeptides are regulated by metabolic signals
      from the gut and the adipose tissue. Furthermore, neurons producing these
      neuropeptides interact with each other, providing neuronal basis of the link
      between energy balance and reproduction. This review summarizes the advances made
      in our understanding of the physiological roles of the hypothalamic neuropeptides
      in energy balance and reproduction in teleosts, and discusses how they interact
      with GnRH, kisspeptin, and pituitary gonadotropins to control reproduction in
      teleosts. 

PMID- 24723915
TI  - Structure and evolution of the magnetochrome domains: no longer alone.
AB  - Magnetotactic bacteria (MTB) can swim along Earth's magnetic field lines, thanks
      to the alignment of dedicated cytoplasmic organelles. These organelles, termed
      magnetosomes, are proteolipidic vesicles filled by a 35-120 nm crystal of either
      magnetite or greigite. The formation and alignment of magnetosomes are mediated
      by a group of specific genes, the mam genes, encoding the magnetosome-associated
      proteins. The whole process of magnetosome biogenesis can be divided into four
      sequential steps; (i) cytoplasmic membrane invagination, (ii) magnetosomes
      alignment, (iii) iron crystal nucleation and (iv) species-dependent mineral size
      and shape control. Since both magnetite and greigite are a mix of iron (III) and
      iron (II), iron redox state management within the magnetosome vesicle is a key
      issue. Recently, studies have started pointing out the importance of a MTB
      specific c-type cytochrome domain found in several magnetosome-associated
      proteins (MamE, P, T, and X). This magnetochrome (MCR) domain is almost always
      found in tandem, and this tandem is either found alone (MamT), in combination
      with a PDZ domain (MamP), a domain of unknown function (MamX) or with a trypsin
      combined to one or two PDZ domains (MamE). By taking advantage of new genomic
      data available on MTB and a recent structural study of MamP, which helped define
      the MCR domain boundaries, we attempt to retrace the evolutionary history within
      and between the different MCR-containing proteins. We propose that the observed
      tandem repeat of MCR is the result of a convergent evolution and attempt to
      explain why this domain is rarely found alone. 

PMID- 24723916
TI  - Perspectives in the use of tannins as alternative to antimicrobial growth
      promoter factors in poultry.
AB  - Antibiotics have been included in the formulation of feed for livestock
      production for more than 40 years as a strategy to improve feed conversion rates
      and to reduce costs. The use of antimicrobials as growth-promoting factors (AGP)
      in sub-therapeutic doses for long periods is particularly favorable for the
      selection of antimicrobial resistant microorganisms. In the last years, global
      concern about development of antimicrobial resistance and transference of
      resistance genes from animal to human strains has been rising. Removal of AGP
      from animal diets involves tremendous pressure on the livestock and poultry
      farmers, one of the main consequences being a substantial increase in the
      incidence of infectious diseases with the associated increase in the use of
      antibiotics for therapy, and concomitantly, economic cost. Therefore,
      alternatives to AGP are urgently needed. The challenge is to implement new
      alternatives without affecting the production performances of livestock and
      avoiding the increase of antimicrobial resistant microorganisms. Plant extracts
      and purified derived substances are showing promising results for animal
      nutrition, either from their efficacy as well as from an economical point of
      view. Tannins are plant derived compounds that are being successfully used as
      additives in poultry feed to control diseases and to improve animal performance.
      Successful use of any of these extracts as feed additives must ensure a product
      of consistent quality in enough quantity to fulfill the actual requirements of
      the poultry industry. Chestnut (hydrolysable) and Quebracho (condensed) tannins
      are probably the most readily available commercial products that are covering
      those needs. The present report intends to analyze the available data supporting
      their use. 

PMID- 24723918
TI  - Life power and art safeguard.

PMID- 24723917
TI  - Phylogenetic diversity of microorganisms in subseafloor crustal fluids from Holes
      1025C and 1026B along the Juan de Fuca Ridge flank.
AB  - To expand investigations into the phylogenetic diversity of microorganisms
      inhabiting the subseafloor biosphere, basalt-hosted crustal fluids were sampled
      from Circulation Obviation Retrofit Kits (CORKs) affixed to Holes 1025C and 1026B
      along the Juan de Fuca Ridge (JdFR) flank using a clean fluid pumping system.
      These boreholes penetrate the crustal aquifer of young ocean crust (1.24 and 3.51
      million years old, respectively), but differ with respect to borehole depth and
      temperature at the sediment-basement interface (147 m and 39 degrees C vs. 295 m
      and 64 degrees C, respectively). Cloning and sequencing of PCR-amplified small
      subunit ribosomal RNA genes revealed that fluids retrieved from Hole 1025C were
      dominated by relatives of the genus Desulfobulbus of the Deltaproteobacteria (56%
      of clones) and Candidatus Desulforudis of the Firmicutes (17%). Fluids sampled
      from Hole 1026B also contained plausible deep subseafloor inhabitants amongst the
      most abundant clone lineages; however, both geochemical analysis and microbial
      community structure reveal the borehole to be compromised by bottom seawater
      intrusion. Regardless, this study provides independent support for previous
      observations seeking to identify phylogenetic groups of microorganisms common to
      the deep ocean crustal biosphere, and extends previous observations by
      identifying additional lineages that may be prevalent in this unique environment.

PMID- 24723919
TI  - Spatial variations of community structures and methane cycling across a transect
      of Lei-Gong-Hou mud volcanoes in eastern Taiwan.
AB  - This study analyzed cored sediments retrieved from sites distributed across a
      transect of the Lei-Gong-Hou mud volcanoes in eastern Taiwan to uncover the
      spatial distributions of biogeochemical processes and community assemblages
      involved in methane cycling. The profiles of methane concentration and carbon
      isotopic composition revealed various orders of the predominance of specific
      methane-related metabolisms along depth. At a site proximal to the bubbling pool,
      the methanogenic zone was sandwiched by the anaerobic methanotrophic zones. For
      two sites distributed toward the topographic depression, the methanogenic zone
      overlaid the anaerobic methanotrophic zone. The predominance of anaerobic
      methanotrophy at specific depth intervals is supported by the enhanced copy
      numbers of the ANME-2a 16S rRNA gene and coincides with high dissolved Fe/Mn
      concentrations and copy numbers of the Desulfuromonas/Pelobacter 16S rRNA gene.
      Assemblages of 16S rRNA and mcrA genes revealed that methanogenesis was mediated
      by Methanococcoides and Methanosarcina. pmoA genes and a few 16S rRNA genes
      related to aerobic methanotrophs were detected in limited numbers of subsurface
      samples. While dissolved Fe/Mn signifies the presence of anaerobic metabolisms
      near the surface, the correlations between geochemical characteristics and gene
      abundances, and the absence of aerobic methanotrophs in top sediments suggest
      that anaerobic methanotrophy is potentially dependent on iron/manganese reduction
      and dominates over aerobic methanotrophy for the removal of methane produced in
      situ or from a deep source. Near-surface methanogenesis contributes to the
      methane emissions from mud platform. The alternating arrangements of methanogenic
      and methanotrophic zones at different sites suggest that the interactions between
      mud deposition, evaporation, oxidation and fluid transport modulate the
      assemblages of microbial communities and methane cycling in different
      compartments of terrestrial mud volcanoes. 

PMID- 24723920
TI  - The haloarchaeal MCM proteins: bioinformatic analysis and targeted mutagenesis of
      the beta7-beta8 and beta9-beta10 hairpin loops and conserved zinc binding domain
      cysteines.
AB  - The hexameric MCM complex is the catalytic core of the replicative helicase in
      eukaryotic and archaeal cells. Here we describe the first in vivo analysis of
      archaeal MCM protein structure and function relationships using the genetically
      tractable haloarchaeon Haloferax volcanii as a model system. Hfx. volcanii
      encodes a single MCM protein that is part of the previously identified core group
      of haloarchaeal MCM proteins. Three structural features of the N-terminal domain
      of the Hfx. volcanii MCM protein were targeted for mutagenesis: the beta7-beta8
      and beta9-beta10 beta-hairpin loops and putative zinc binding domain. Five
      strains carrying single point mutations in the beta7-beta8 beta-hairpin loop were
      constructed, none of which displayed impaired cell growth under normal conditions
      or when treated with the DNA damaging agent mitomycin C. However, short sequence
      deletions within the beta7-beta8 beta-hairpin were not tolerated and neither was
      replacement of the highly conserved residue glutamate 187 with alanine. Six
      strains carrying paired alanine substitutions within the beta9-beta10 beta
      hairpin loop were constructed, leading to the conclusion that no individual amino
      acid within that hairpin loop is absolutely required for MCM function, although
      one of the mutant strains displays greatly enhanced sensitivity to mitomycin C.
      Deletions of two or four amino acids from the beta9-beta10 beta-hairpin were
      tolerated but mutants carrying larger deletions were inviable. Similarly, it was
      not possible to construct mutants in which any of the conserved zinc binding
      cysteines was replaced with alanine, underlining the likely importance of zinc
      binding for MCM function. The results of these studies demonstrate the
      feasibility of using Hfx. volcanii as a model system for reverse genetic analysis
      of archaeal MCM protein function and provide important confirmation of the in
      vivo importance of conserved structural features identified by previous
      bioinformatic, biochemical and structural studies. 

PMID- 24723921
TI  - A mathematical model of metabolism and regulation provides a systems-level view
      of how Escherichia coli responds to oxygen.
AB  - The efficient redesign of bacteria for biotechnological purposes, such as biofuel
      production, waste disposal or specific biocatalytic functions, requires a
      quantitative systems-level understanding of energy supply, carbon, and redox
      metabolism. The measurement of transcript levels, metabolite concentrations and
      metabolic fluxes per se gives an incomplete picture. An appreciation of the
      interdependencies between the different measurement values is essential for
      systems-level understanding. Mathematical modeling has the potential to provide a
      coherent and quantitative description of the interplay between gene expression,
      metabolite concentrations, and metabolic fluxes. Escherichia coli undergoes major
      adaptations in central metabolism when the availability of oxygen changes. Thus,
      an integrated description of the oxygen response provides a benchmark of our
      understanding of carbon, energy, and redox metabolism. We present the first
      comprehensive model of the central metabolism of E. coli that describes steady
      state metabolism at different levels of oxygen availability. Variables of the
      model are metabolite concentrations, gene expression levels, transcription factor
      activities, metabolic fluxes, and biomass concentration. We analyze the model
      with respect to the production capabilities of central metabolism of E. coli. In
      particular, we predict how precursor and biomass concentration are affected by
      product formation. 

PMID- 24723922
TI  - Toward quantitative understanding on microbial community structure and
      functioning: a modeling-centered approach using degradation of marine oil spills
      as example.
AB  - Molecular ecology approaches are rapidly advancing our insights into the
      microorganisms involved in the degradation of marine oil spills and their
      metabolic potentials. Yet, many questions remain open: how do oil-degrading
      microbial communities assemble in terms of functional diversity, species
      abundances and organization and what are the drivers? How do the functional
      properties of microorganisms scale to processes at the ecosystem level? How does
      mass flow among species, and which factors and species control and regulate
      fluxes, stability and other ecosystem functions? Can generic rules on oil
      degradation be derived, and what drivers underlie these rules? How can we
      engineer oil-degrading microbial communities such that toxic polycyclic aromatic
      hydrocarbons are degraded faster? These types of questions apply to the field of
      microbial ecology in general. We outline how recent advances in single-species
      systems biology might be extended to help answer these questions. We argue that
      bottom-up mechanistic modeling allows deciphering the respective roles and
      interactions among microorganisms. In particular constraint-based, metagenome
      derived community-scale flux balance analysis appears suited for this goal as it
      allows calculating degradation-related fluxes based on physiological constraints
      and growth strategies, without needing detailed kinetic information. We
      subsequently discuss what is required to make these approaches successful, and
      identify a need to better understand microbial physiology in order to advance
      microbial ecology. We advocate the development of databases containing microbial
      physiological data. Answering the posed questions is far from trivial. Oil
      degrading communities are, however, an attractive setting to start testing
      systems biology-derived models and hypotheses as they are relatively simple in
      diversity and key activities, with several key players being isolated and a high
      availability of experimental data and approaches. 

PMID- 24723923
TI  - Structural basis for recognition of cellular and viral ligands by NK cell
      receptors.
AB  - Natural killer (NK) cells are key components of innate immune responses to tumors
      and viral infections. NK cell function is regulated by NK cell receptors that
      recognize both cellular and viral ligands, including major histocompatibility
      complex (MHC), MHC-like, and non-MHC molecules. These receptors include Ly49s,
      killer immunoglobulin-like receptors, leukocyte immunoglobulin-like receptors,
      and NKG2A/CD94, which bind MHC class I (MHC-I) molecules, and NKG2D, which binds
      MHC-I paralogs such as the stress-induced proteins MICA and ULBP. In addition,
      certain viruses have evolved MHC-like immunoevasins, such as UL18 and m157 from
      cytomegalovirus, that act as decoy ligands for NK receptors. A growing number of
      NK receptor-ligand interaction pairs involving non-MHC molecules have also been
      identified, including NKp30-B7-H6, killer cell lectin-like receptor G1-cadherin,
      and NKp80-AICL. Here, we describe crystal structures determined to date of NK
      cell receptors bound to MHC, MHC-related, and non-MHC ligands. Collectively,
      these structures reveal the diverse solutions that NK receptors have developed to
      recognize these molecules, thereby enabling the regulation of NK cytolytic
      activity by both host and viral ligands. 

PMID- 24723925
TI  - Divergent functions of the Arabidopsis mitochondrial SCO proteins: HCC1 is
      essential for COX activity while HCC2 is involved in the UV-B stress response.
AB  - The two related putative cytochrome c oxidase (COX) assembly factors HCC1 and
      HCC2 from Arabidopsis thaliana are Homologs of the yeast Copper Chaperones Sco1p
      and Sco2p. The hcc1 null mutation was previously shown to be embryo lethal while
      the disruption of the HCC2 gene function had no obvious effect on plant
      development, but increased the expression of stress-responsive genes. Both HCC1
      and HCC2 contain a thioredoxin domain, but only HCC1 carries a Cu-binding motif
      also found in Sco1p and Sco2p. In order to investigate the physiological
      implications suggested by this difference, various hcc1 and hcc2 mutants were
      generated and analyzed. The lethality of the hcc1 knockout mutation was rescued
      by complementation with the HCC1 gene under the control of the embryo-specific
      promoter ABSCISIC ACID INSENSITIVE 3. However, the complemented seedlings did not
      grow into mature plants, underscoring the general importance of HCC1 for plant
      growth. The HCC2 homolog was shown to localize to mitochondria like HCC1, yet the
      function of HCC2 is evidently different, because two hcc2 knockout lines
      developed normally and exhibited only mild growth suppression compared with the
      wild type (WT). However, hcc2 knockouts were more sensitive to UV-B treatment
      than the WT. Complementation of the hcc2 knockout with HCC2 rescued the UV-B
      sensitive phenotype. In agreement with this, exposure of wild-type plants to UV-B
      led to an increase of HCC2 transcripts. In order to corroborate a function of
      HCC1 and HCC2 in COX biogenesis, COX activity of hcc1 and hcc2 mutants was
      compared. While the loss of HCC2 function had no significant effect on COX
      activity, the disruption of one HCC1 gene copy was enough to suppress respiration
      by more than half compared with the WT. Therefore, we conclude that HCC1 is
      essential for COX function, most likely by delivering Cu to the catalytic center.
      HCC2, on the other hand, seems to be involved directly or indirectly in UV-B
      stress responses. 

PMID- 24723926
TI  - Memory of the vernalized state in plants including the model grass Brachypodium
      distachyon.
AB  - Plant species that have a vernalization requirement exhibit variation in the
      ability to "remember" winter - i.e., variation in the stability of the vernalized
      state. Studies in Arabidopsis have demonstrated that molecular memory involves
      changes in the chromatin state and expression of the flowering repressor
      FLOWERING LOCUS C, and have revealed that single-gene differences can have large
      effects on the stability of the vernalized state. In the perennial Arabidopsis
      relative Arabis alpina, the lack of memory of winter is critical for its
      perennial life history. Our studies of flowering behavior in the model grass
      Brachypodium distachyon reveal extensive variation in the vernalization
      requirement, and studies of a particular Brachypodium accession that has a
      qualitative requirement for both cold exposure and inductive day length to flower
      reveal that Brachypodium can exhibit a highly stable vernalized state. 

PMID- 24723927
TI  - Root iron uptake efficiency of Ulmus laevis and U. minor and their distribution
      in soils of the Iberian Peninsula.
AB  - The calcifuge and calcicole character of wild plants has been related to nutrient
      availability shortages, including iron (Fe)-deficiency. Surprisingly, just a few
      studies examined the relation between root Fe uptake and plant distribution in
      different soil types. We assessed the root Fe acquisition efficiency of two Ulmus
      species with calcareous (Ulmus minor) and siliceous (U. laevis) soil distribution
      patterns in the Iberian Peninsula. Seedlings of both elm species were grown
      hydroponically with different Fe concentrations during 6 weeks. Plant
      physiological responses to Fe-limiting conditions were evaluated as were the
      ferric reductase activity and proton (H(+)) extrusion capacity of the roots. Iron
      deprived elm seedlings of both species were stunted and suffered severe Fe
      chlorosis symptoms. After Fe re-supply leaf chlorophyll concentrations rose
      according to species-dependent patterns. While U. minor leaves and seedlings re
      greened evenly, U. laevis did so along the nerves of new growing leaves. U. minor
      had a higher root ferric reductase activity and H(+)-extrusion capability than U.
      laevis and maintained a better nutrient balance when grown under Fe-limiting
      conditions. The two elm species were found to have different Fe acquisition
      efficiencies which may be related to their natural distribution in calcareous and
      siliceous soils of the Iberian Peninsula. 

PMID- 24723924
TI  - Mechanisms driving macrophage diversity and specialization in distinct tumor
      microenvironments and parallelisms with other tissues.
AB  - Macrophages are extremely versatile cells that adopt a distinct phenotype in
      response to a changing microenvironment. Consequently, macrophages are involved
      in diverse functions, ranging from organogenesis and tissue homeostasis to
      recognition and destruction of invading pathogens. In cancer, tumor-associated
      macrophages (TAM) often contribute to tumor progression by increasing cancer cell
      migration and invasiveness, stimulating angiogenesis, and suppressing anti-tumor
      immunity. Accumulating evidence suggests that these different functions could be
      exerted by specialized TAM subpopulations. Here, we discuss the potential
      underlying mechanisms regulating TAM specialization and elaborate on TAM
      heterogeneity in terms of their ontogeny, activation state, and intra-tumoral
      localization. In addition, parallels are drawn between TAM and macrophages in
      other tissues. Together, a better understanding of TAM diversity could provide a
      rationale for novel strategies aimed at targeting the most potent tumor
      supporting macrophages. 

PMID- 24723929
TI  - Development of endosperm transfer cells in barley.
AB  - Endosperm transfer cells (ETCs) are positioned at the intersection of maternal
      and filial tissues in seeds of cereals and represent a bottleneck for apoplasmic
      transport of assimilates into the endosperm. Endosperm cellularization starts at
      the maternal-filial boundary and generates the highly specialized ETCs. During
      differentiation barley ETCs develop characteristic flange-like wall ingrowths to
      facilitate effective nutrient transfer. A comprehensive morphological analysis
      depicted distinct developmental time points in establishment of transfer cell
      (TC) morphology and revealed intracellular changes possibly associated with cell
      wall metabolism. Embedded inside the grain, ETCs are barely accessible by manual
      preparation. To get tissue-specific information about ETC specification and
      differentiation, laser microdissection (LM)-based methods were used for
      transcript and metabolite profiling. Transcriptome analysis of ETCs at different
      developmental stages by microarrays indicated activated gene expression programs
      related to control of cell proliferation and cell shape, cell wall and
      carbohydrate metabolism reflecting the morphological changes during early ETC
      development. Transporter genes reveal distinct expression patterns suggesting a
      switch from active to passive modes of nutrient uptake with the onset of grain
      filling. Tissue-specific RNA-seq of the differentiating ETC region from the
      syncytial stage until functionality in nutrient transfer identified a high number
      of novel transcripts putatively involved in ETC differentiation. An essential
      role for two-component signaling (TCS) pathways in ETC development of barley
      emerged from this analysis. Correlative data provide evidence for abscisic acid
      and ethylene influences on ETC differentiation and hint at a crosstalk between
      hormone signal transduction and TCS phosphorelays. Collectively, the data expose
      a comprehensive view on ETC development, associated pathways and identified
      candidate genes for ETC specification. 

PMID- 24723928
TI  - Metal species involved in long distance metal transport in plants.
AB  - The mechanisms plants use to transport metals from roots to shoots are not
      completely understood. It has long been proposed that organic molecules
      participate in metal translocation within the plant. However, until recently the
      identity of the complexes involved in the long-distance transport of metals could
      only be inferred by using indirect methods, such as analyzing separately the
      concentrations of metals and putative ligands and then using in silico chemical
      speciation software to predict metal species. Molecular biology approaches also
      have provided a breadth of information about putative metal ligands and metal
      complexes occurring in plant fluids. The new advances in analytical techniques
      based on mass spectrometry and the increased use of synchrotron X-ray
      spectroscopy have allowed for the identification of some metal-ligand species in
      plant fluids such as the xylem and phloem saps. Also, some proteins present in
      plant fluids can bind metals and a few studies have explored this possibility.
      This study reviews the analytical challenges researchers have to face to
      understand long-distance metal transport in plants as well as the recent advances
      in the identification of the ligand and metal-ligand complexes in plant fluids. 

PMID- 24723930
TI  - Membrane lipids in Agrobacterium tumefaciens: biosynthetic pathways and
      importance for pathogenesis.
AB  - Many cellular processes critically depend on the membrane composition. In this
      review, we focus on the biosynthesis and physiological roles of membrane lipids
      in the plant pathogen Agrobacterium tumefaciens. The major components of A.
      tumefaciens membranes are the phospholipids (PLs), phosphatidylethanolamine (PE),
      phosphatidylglycerol, phosphatidylcholine (PC) and cardiolipin, and ornithine
      lipids (OLs). Under phosphate-limited conditions, the membrane composition shifts
      to phosphate-free lipids like glycolipids, OLs and a betaine lipid. Remarkably,
      PC and OLs have opposing effects on virulence of A. tumefaciens. OL-lacking A.
      tumefaciens mutants form tumors on the host plant earlier than the wild type
      suggesting a reduced host defense response in the absence of OLs. In contrast, A.
      tumefaciens is compromised in tumor formation in the absence of PC. In general,
      PC is a rare component of bacterial membranes but amount to ~22% of all PLs in A.
      tumefaciens. PC biosynthesis occurs via two pathways. The phospholipid N
      methyltransferase PmtA methylates PE via the intermediates monomethyl-PE and
      dimethyl-PE to PC. In the second pathway, the membrane-integral enzyme PC
      synthase (Pcs) condenses choline with CDP-diacylglycerol to PC. Apart from the
      virulence defect, PC-deficient A. tumefaciens pmtA and pcs double mutants show
      reduced motility, enhanced biofilm formation and increased sensitivity towards
      detergent and thermal stress. In summary, there is cumulative evidence that the
      membrane lipid composition of A. tumefaciens is critical for agrobacterial
      physiology and tumor formation. 

PMID- 24723932
TI  - Sugar sensing and signaling in plants.

PMID- 24723931
TI  - Intracellular coordination of potyviral RNA functions in infection.
AB  - Establishment of an infection cycle requires mechanisms to allocate the genomes
      of (+)-stranded RNA viruses in a balanced ratio to translation, replication,
      encapsidation, and movement, as well as mechanisms to prevent translocation of
      viral RNA (vRNA) to cellular RNA degradation pathways. The ratio of vRNA
      allocated to various functions is likely balanced by the availability of
      regulatory proteins or competition of the interaction sites within regulatory
      ribonucleoprotein complexes. Due to the transient nature of viral processes and
      the interdependency between vRNA pathways, it is technically demanding to work
      out the exact molecular mechanisms underlying vRNA regulation. A substantial
      number of viral and host proteins have been identified that facilitate the steps
      that lead to the assembly of a functional potyviral RNA replication complex and
      their fusion with chloroplasts. Simultaneously with on-going viral replication,
      part of the replicated potyviral RNA enters movement pathways. Although not much
      is known about the processes of potyviral RNA release from viral replication
      complexes, the molecular interactions involved in these processes determine the
      fate of the replicated vRNA. Some viral and host cell proteins have been
      described that direct replicated potyviral RNA to translation to enable potyviral
      gene expression and productive infection. The antiviral defense of the cell
      causes vRNA degradation by RNA silencing. We hypothesize that also plant pathways
      involved in mRNA decay may have a role in the coordination of potyviral RNA
      expression. In this review, we discuss the roles of different potyviral and host
      proteins in the coordination of various potyviral RNA functions. 

PMID- 24723934
TI  - Ovule development, a new model for lateral organ formation.
AB  - In spermatophytes the ovules upon fertilization give rise to the seeds. It is
      essential to understand the mechanisms that control ovule number and development
      as they ultimately determine the final number of seeds and, thereby, the yield in
      crop plants. In Arabidopsis thaliana, ovules arise laterally from a meristematic
      tissue within the carpel referred to as placenta. For a correct determination of
      the number of ovules, a precise establishment of the positions where ovule
      primordia emerge is needed, and a tight definition of the boundaries between
      ovules is therefore also required. In the last decades, few factors have been
      identified to be involved in the determination of ovule number. Recently, plant
      hormones have also been revealed as fundamental players in the control of the
      initiation of ovule formation. In this review we summarize the current knowledge
      about both the molecular and hormonal mechanisms that control ovule formation in
      Arabidopsis thaliana. 

PMID- 24723933
TI  - Commonalities and differences of T3SSs in rhizobia and plant pathogenic bacteria.
AB  - Plant pathogenic bacteria and rhizobia infect higher plants albeit the
      interactions with their hosts are principally distinct and lead to completely
      different phenotypic outcomes, either pathogenic or mutualistic, respectively.
      Bacterial protein delivery to plant host plays an essential role in determining
      the phenotypic outcome of plant-bacteria interactions. The involvement of type
      III secretion systems (T3SSs) in mediating animal- and plant-pathogen
      interactions was discovered in the mid-80's and is now recognized as a
      multiprotein nanomachine dedicated to trans-kingdom movement of effector
      proteins. The discovery of T3SS in bacteria with symbiotic lifestyles broadened
      its role beyond virulence. In most T3SS-positive bacterial pathogens, virulence
      is largely dependent on functional T3SSs, while in rhizobia the system is
      dispensable for nodulation and can affect positively or negatively the
      mutualistic associations with their hosts. This review focuses on recent
      comparative genome analyses in plant pathogens and rhizobia that uncovered
      similarities and variations among T3SSs in their genetic organization, regulatory
      networks and type III secreted proteins and discusses the evolutionary
      adaptations of T3SSs and type III secreted proteins that might account for the
      distinguishable phenotypes and host range characteristics of plant pathogens and
      symbionts. 

PMID- 24723935
TI  - Return of results in the genomic medicine projects of the eMERGE network.
AB  - The electronic Medical Records and Genomics (eMERGE) (Phase I) network was
      established in 2007 to further genomic discovery using biorepositories linked to
      the electronic health record (EHR). In Phase II, which began in 2011, genomic
      discovery efforts continue and in addition the network is investigating best
      practices for implementing genomic medicine, in particular, the return of genomic
      results in the EHR for use by physicians at point-of-care. To develop strategies
      for addressing the challenges of implementing genomic medicine in the clinical
      setting, the eMERGE network is conducting studies that return clinically-relevant
      genomic results to research participants and their health care providers. These
      genomic medicine pilot studies include returning individual genetic variants
      associated with disease susceptibility or drug response, as well as genetic risk
      scores for common "complex" disorders. Additionally, as part of a network-wide
      pharmacogenomics-related project, targeted resequencing of 84 pharmacogenes is
      being performed and select genotypes of pharmacogenetic relevance are being
      placed in the EHR to guide individualized drug therapy. Individual sites within
      the eMERGE network are exploring mechanisms to address incidental findings
      generated by resequencing of the 84 pharmacogenes. In this paper, we describe
      studies being conducted within the eMERGE network to develop best practices for
      integrating genomic findings into the EHR, and the challenges associated with
      such work. 

PMID- 24723936
TI  - Oncofinder, a new method for the analysis of intracellular signaling pathway
      activation using transcriptomic data.
AB  - We propose a new biomathematical method, OncoFinder, for both quantitative and
      qualitative analysis of the intracellular signaling pathway activation (SPA).
      This method is universal and may be used for the analysis of any physiological,
      stress, malignancy and other perturbed conditions at the molecular level. In
      contrast to the other existing techniques for aggregation and generalization of
      the gene expression data for individual samples, we suggest to distinguish the
      positive/activator and negative/repressor role of every gene product in each
      pathway. We show that the relative importance of each gene product in a pathway
      can be assessed using kinetic models for "low-level" protein interactions.
      Although the importance factors for the pathway members cannot be so far
      established for most of the signaling pathways due to the lack of the required
      experimental data, we showed that ignoring these factors can be sometimes
      acceptable and that the simplified formula for SPA evaluation may be applied for
      many cases. We hope that due to its universal applicability, the method
      OncoFinder will be widely used by the researcher community. 

PMID- 24723938
TI  - CYP2C8 and CYP2C9 mRNA expression profile in the human fetus.
AB  - CYP2C8 and CYP2C9 are involved in the inactivation of several non-steroidal anti
      inflammatory drugs, including ibuprofen. CYP2C9 is the major form in human liver
      whereas CYP2C8 has been proposed to be the main CYP2C enzyme in fetal liver. The
      protein expression of CYP2C9 in the first trimester is low, only about 1% of the
      adult values, whereas the mRNA levels of CYP2C8/9 have not been determined at the
      fetal stage. In this study the mRNA expression levels of CYP2C8 and CYP2C9 were
      determined in 20 adult and 60 fetal liver tissue specimens. The expression
      profiles in fetal kidneys (n = 43), adrenals (n = 46), and lungs (n = 37) were
      also determined. Moreover the activity against ibuprofen hydroxylation was
      determined in fetus and adult liver microsomes. Adult liver samples expressed 140
      and 400 times higher levels of CYP2C8 and CYP2C9 mRNA, respectively, as compared
      to fetal liver samples. Consistent with this, the hydroxylation of ibuprofen was
      40 times higher in the adult liver microsomes. Hepatic CYP2C8 mRNA was three
      times more abundant than CYP2C9 mRNA in the fetus. Moreover, CYP2C8 were
      consistently expressed in all fetal tissues investigated, whereas CYP2C9 gene
      expression was confined to the liver in fetuses. Our results indicate that CYP2C8
      plays a more important physiological role than CYP2C9 in the first trimester. 

PMID- 24723937
TI  - Regulation of metabolism by long, non-coding RNAs.
AB  - Our understanding of genomic regulation was revolutionized by the discovery that
      the genome is pervasively transcribed, giving rise to thousands of mostly
      uncharacterized non-coding ribonucleic acids (ncRNAs). Long, ncRNAs (lncRNAs)
      have thus emerged as a novel class of functional RNAs that impinge on gene
      regulation by a broad spectrum of mechanisms such as the recruitment of
      epigenetic modifier proteins, control of mRNA decay and DNA sequestration of
      transcription factors. We review those lncRNAs that are implicated in
      differentiation and homeostasis of metabolic tissues and present novel concepts
      on how lncRNAs might act on energy and glucose homeostasis. Finally, the control
      of circadian rhythm by lncRNAs is an emerging principles of lncRNA-mediated gene
      regulation. 

PMID- 24723939
TI  - Oxidative stress and age-related olfactory memory impairment in the honeybee Apis
      mellifera.

PMID- 24723941
TI  - Active contour model coupling with higher order diffusion for medical image
      segmentation.
AB  - Active contour models are very popular in image segmentation. Different features
      such as mean gray and variance are selected for different purpose. But for image
      with intensity inhomogeneities, there are no features for segmentation using the
      active contour model. The images with intensity inhomogeneities often occurred in
      real world especially in medical images. To deal with the difficulties raised in
      image segmentation with intensity inhomogeneities, a new active contour model
      with higher-order diffusion method is proposed. With the addition of gradient and
      Laplace information, the active contour model can converge to the edge of the
      image even with the intensity inhomogeneities. Because of the introduction of
      Laplace information, the difference scheme becomes more difficult. To enhance the
      efficiency of the segmentation, the fast Split Bregman algorithm is designed for
      the segmentation implementation. The performance of our method is demonstrated
      through numerical experiments of some medical image segmentations with intensity
      inhomogeneities. 

PMID- 24723942
TI  - Epidermal growth factor receptor inhibitors: a review of cutaneous adverse events
      and management.
AB  - Epidermal growth factor inhibitors (EGFRI), the first targeted cancer therapy,
      are currently an essential treatment for many advance-stage epithelial cancers.
      These agents have the superior ability to target cancers cells and better safety
      profile compared to conventional chemotherapies. However, cutaneous adverse
      events are common due to the interference of epidermal growth factor receptor
      (EGFR) signaling in the skin. Cutaneous toxicities lead to poor compliance, drug
      cessation, and psychosocial discomfort. This paper summarizes the current
      knowledge concerning the presentation and management of skin toxicity from EGFRI.
      The common dermatologic adverse events are papulopustules and xerosis. Less
      common findings are paronychia, regulatory abnormalities of hair growth,
      maculopapular rash, mucositis, and postinflammatory hyperpigmentation. Radiation
      enhances EGFRI rash due to synergistic toxicity. There is a positive correlation
      between the occurrence and severity of cutaneous adverse effects and tumor
      response. To date, prophylactic systemic tetracycline and tetracycline class
      antibiotics have proven to be the most effective treatment regime. 

PMID- 24723943
TI  - Absence of autophagy-related proteins expression is associated with poor
      prognosis in patients with colorectal adenocarcinoma.
AB  - Background/Aim. Autophagy, a cellular degradation process, has paradoxical roles
      in tumorigenesis and the progression of human cancers. The aim of this study was
      to investigate the expression levels of autophagy-related proteins in colorectal
      cancer (CRC) and to evaluate their prognostic significance. Methods. This study
      is a retrospective review of immunohistochemical and clinicopathological data.
      All specimens evaluated were obtained from 263 patients with colorectal cancer
      who had undergone surgery between November 1996 and August 2007. The primary
      outcomes measured were the expression levels of three autophagy-related proteins
      (ATG5, BECN1/Beclin 1, and Microtubule-associated protein 1 light chain 3B
      (LC3B)) by immunohistochemistry and its association in clinicopathological
      parameters and patient survival. Results. The autophagy-related protein
      expression frequencies were 65.1% (151/232) for ATG5, 71.3% (174/244) for BECN1,
      and 74.7% (186/249) for LC3B for the 263 patients. Correlation between the
      expression of autophagy-related proteins was significant for all protein pairs.
      Multivariate analysis showed that negative LC3B expression and absence of
      autophagy-related proteins expression were independently associated with poor
      prognosis. Conclusion. Absence of autophagy-related proteins expression is
      associated with poor clinical outcome in CRC, suggesting that these proteins have
      potential uses as novel prognostic markers. 

PMID- 24723944
TI  - Clinical characteristics and surgical prognosis of hepatocellular carcinoma with
      bile duct invasion.
AB  - Objectives. Bile duct invasion (BDI) is a rare event in hepatocellular carcinoma
      (HCC). The present study aimed at investigating clinical characteristics and
      surgical outcome of HCC patients with bile duct invasion. Methods. 413 patients
      with HCC undergoing curative surgery were divided into two groups with (B(+)) and
      without BDI (B(-)). BDI was further classified as central type (B1) and
      peripheral type (B2). Survival was compared, and risk factors affecting prognosis
      were identified. Results. 35 (8.5%) patients were diagnosed BDI. Total bilirubin
      was significantly higher in B(+) group than in B(-) group (P < 0.001). Multiple
      lesions and large nodules (>5 cm) were predominantly identified in B(+) group (P
      < 0.01, resp.). Portal vein invasion was more frequently observed in B(+) than in
      B(-) group (P = 0.003). Univariate and multivariate analyses identified central
      BDI as a significant factor affecting prognosis of HCC patients (risk 1.3, 95% CI
      1.1-2.2, P = 0.015). The gross overall survival of patients in B(+) was
      significantly worse than in B(-) (P = 0.001), which, however, was not different
      between B2 and B(-) (P > 0.05). Conclusions. Central but not peripheral BDI was
      associated with poorer prognosis of HCC patients. Curative surgical resection of
      tumors and invaded bile duct supplies the only hope for long-term survival of
      patients. 

PMID- 24723945
TI  - Inhibitory Potential of Five Traditionally Used Native Antidiabetic Medicinal
      Plants on alpha -Amylase, alpha -Glucosidase, Glucose Entrapment, and Amylolysis
      Kinetics In Vitro.
AB  - Five traditionally used antidiabetic native medicinal plants of Mauritius,
      namely, Stillingia lineata (SL), Faujasiopsis flexuosa (FF), Erythroxylum
      laurifolium (EL), Elaeodendron orientale (EO), and Antidesma madagascariensis
      (AM), were studied for possible alpha -amylase and alpha -glucosidase inhibitory
      property, glucose entrapment, and amylolysis kinetics in vitro. Only methanolic
      extracts of EL, EO, and AM (7472.92 +/- 5.99, 1745.58 +/- 31.66, and 2222.96 +/-
      13.69  MU g/mL, resp.) were found to significantly (P < 0.05) inhibit alpha 
      amylase and were comparable to acarbose. EL, EO, AM, and SL extracts (5000  MU
      g/mL) were found to significantly (P < 0.05) inhibit alpha -glucosidase (between
      87.41 +/- 3.31 and 96.87 +/- 1.37% inhibition). Enzyme kinetic studies showed an
      uncompetitive and mixed type of inhibition. Extracts showed significant (P <
      0.05) glucose entrapment capacities (8 to 29% glucose diffusion retardation index
      (GDRI)), with SL being more active (29% GDRI) and showing concentration-dependent
      activity (29, 26, 21, 14, and 5%, resp.). Amylolysis kinetic studies showed that
      methanolic extracts were more potent inhibitors of alpha -amylase compared to
      aqueous extracts and possessed glucose entrapment properties. Our findings tend
      to provide justification for the hypoglycaemic action of these medicinal plants
      which has opened novel avenues for the development of new phytopharmaceuticals
      geared towards diabetes management. 

PMID- 24723946
TI  - Controversies in the anesthetic management of intraoperative rupture of
      intracranial aneurysm.
AB  - Despite great advancements in the management of aneurysmal subarachnoid
      hemorrhage (SAH), outcomes following SAH rupture have remained relatively
      unchanged. In addition, little data exists to guide the anesthetic management of
      intraoperative aneurysm rupture (IAR), though intraoperative management may have
      a significant effect on overall neurological outcomes. This review highlights the
      various controversies related to different anesthetic management related to
      aneurysm rupture. The first controversy relates to management of preexisting
      factors that affect risk of IAR. The second controversy relates to diagnostic
      techniques, particularly neurophysiological monitoring. The third controversy
      pertains to hemodynamic goals. The neuroprotective effects of various factors,
      including hypothermia, various anesthetic/pharmacologic agents, and burst
      suppression, remain poorly understood and have yet to be further elucidated.
      Different management strategies for IAR during aneurysmal clipping versus coiling
      also need further attention. 

PMID- 24723947
TI  - Multilocus Sequence Typing for Interpreting Blood Isolates of Staphylococcus
      epidermidis.
AB  - Staphylococcus epidermidis is an important cause of nosocomial infection and
      bacteremia. It is also a common contaminant of blood cultures and, as a result,
      there is frequently uncertainty as to its diagnostic significance when recovered
      in the clinical laboratory. One molecular strategy that might be of value in
      clarifying the interpretation of S. epidermidis identified in blood culture is
      multilocus sequence typing. Here, we examined 100 isolates of this species (50
      blood isolates representing true bacteremia, 25 likely contaminant isolates, and
      25 skin isolates) and the ability of sequence typing to differentiate them. Three
      machine learning algorithms (classification regression tree, support vector
      machine, and nearest neighbor) were employed. Genetic variability was substantial
      between isolates, with 44 sequence types found in 100 isolates. Sequence types 2
      and 5 were most commonly identified. However, among the classification algorithms
      we employed, none were effective, with CART and SVM both yielding only 73%
      diagnostic accuracy and nearest neighbor analysis yielding only 53% accuracy. Our
      data mirror previous studies examining the presence or absence of pathogenic
      genes in that the overlap between truly significant organisms and contaminants
      appears to prevent the use of MLST in the clarification of blood cultures
      recovering S. epidermidis. 

PMID- 24723949
TI  - Decreased Expression of Thyroglobulin and Sodium Iodide Symporter Genes in
      Hashimoto's Thyroiditis.
AB  - Aim. The aim of the study was to compare the expression of sodium iodide
      symporter (NIS), thyroglobulin (Tg), tumor necrosis factor- alpha (TNF alpha ),
      and interleukin-1 beta genes in patients with Hashimoto's thyroiditis (HT) and
      healthy individuals. Subjects and Methods. Thyroid cells were obtained from 39
      patients with HT and 15 controls by an ultrasound guided fine needle aspiration
      biopsy. Results. The patients with HT had lower Tg and NIS mRNA (P = 0.002 and P
      = 0.001, resp.), as well as higher TNF alpha mRNA expression (P = 0.049) than the
      controls. In the HT group Tg mRNA expression correlated positively with NIS mRNA
      expression (R = 0.739, P = 0.0001) and thyroid volume (R = 0.465, P = 0.0005), as
      well as negatively with TNF alpha mRNA expression (R = -0.490, P = 0.001) and
      anti-peroxidase antibodies (TPOAb) level (R = -0.482, P = 0.0002), whereas NIS
      mRNA expression correlated positively with thyroid volume (R = 0.319, P = 0.02),
      as well as negatively with TNF alpha mRNA expression (R = -0.529, P = 0.0006) and
      TPOAb level (R = -0.422, P = 0.001). Conclusions. Our results suggest that
      decreased Tg and NIS expression in thyroid cells may result in reduced active
      iodide transport and reduced thyroid volume in patients with HT. 

PMID- 24723948
TI  - The Interplay between Magnesium and Testosterone in Modulating Physical Function
      in Men.
AB  - The role of nutritional status as key factor of successful aging is very well
      recognized. Among the different mechanisms by which nutrients may exert their
      beneficial effects is the modulation of the hormonal anabolic milieu, which is
      significantly reduced with aging. Undernutrition and anabolic hormonal deficiency
      frequently coexist in older individuals determining an increased risk of mobility
      impairment and other adverse outcomes. Mineral assessment has received attention
      as an important determinant of physical performance. In particular, there is
      evidence that magnesium exerts a positive influence on anabolic hormonal status,
      including Testosterone, in men. In this review we summarize data from
      observational and intervention studies about the role of magnesium in
      Testosterone bioactivity and the potential underlying mechanisms of this
      relationship in male subjects. If larger studies will confirm these pivotal data,
      the combination of hormonal and mineral replacements might be adopted to prevent
      or delay the onset of disability in the elderly. 

PMID- 24723950
TI  - Distribution of abdominal obesity and fitness level in overweight and obese
      korean adults.
AB  - Background. Abdominal obesity and its relative distribution are known to differ
      in association with metabolic characteristics and cardiorespiratory fitness. This
      study aimed to determine an association between fitness level and abdominal
      adiposity in overweight and obese adults. Methods. 228 overweight and obese
      individuals were classified as either cardiorespiratory unfit or fit based on
      their recovery heart rate. Visceral adipose tissue (VAT), subcutaneous adipose
      tissue (SAT), the visceral-to-subcutaneous adipose tissue ratio (VAT/SAT ratio),
      and cardiometabolic characteristics were analyzed to examine the relationship
      between recovery heart rate and abdominal adiposity components. Results. After
      adjustments for age and sex, significant relationships of recovery heart rate and
      VAT, SAT, and VAT/SAT ratio were found; however, SAT was not significantly
      associated after further adjustment for body mass index (BMI) (r = 0.045, P =
      0.499), whereas VAT (r = 0.232, P < 0.001) and VAT/SAT ratio (r = 0.214, P =
      0.001) remained associated. Through stepwise multiple regression analyses after
      adjustment for age, sex, BMI, lifestyle factors, mean blood pressure, fasting
      glucose, HOMA-IR, lipid profiles, and hsCRP, recovery heart rate was identified
      as an independent variable associated with VAT (beta = 0.204, P < 0.001) and
      VAT/SAT ratio (beta = 0.163, P = 0.008) but not with SAT (beta = 0.097, P =
      0.111). Conclusions. Cardiorespiratory fitness level is independently associated
      with VAT and the VAT/SAT ratio but not with SAT in overweight and obese adults. 

PMID- 24723951
TI  - Irisin enhances osteoblast differentiation in vitro.
AB  - It has been recently demonstrated that exercise activity increases the expression
      of the myokine Irisin in skeletal muscle, which is able to drive the transition
      of white to brown adipocytes, likely following a phenomenon of
      transdifferentiation. This new evidence supports the idea that muscle can be
      considered an endocrine organ, given its ability to target adipose tissue by
      promoting energy expenditure. In accordance with these new findings, we
      hypothesized that Irisin is directly involved in bone metabolism, demonstrating
      its ability to increase the differentiation of bone marrow stromal cells into
      mature osteoblasts. Firstly, we confirmed that myoblasts from mice subjected to 3
      weeks of free wheel running increased Irisin expression compared to nonexercised
      state. The conditioned media (CM) collected from myoblasts of exercised mice
      induced osteoblast differentiation in vitro to a greater extent than those of
      mice housed in resting conditions. Furthermore, the differentiated osteoblasts
      increased alkaline phosphatase and collagen I expression by an Irisin-dependent
      mechanism. Our results show, for the first time, that Irisin directly targets
      osteoblasts, enhancing their differentiation. This finding advances notable
      perspectives in future studies which could satisfy the ongoing research of
      exercise-mimetic therapies with anabolic action on the skeleton. 

PMID- 24723952
TI  - Evaluation of bone healing on sandblasted and Acid etched implants coated with
      nanocrystalline hydroxyapatite: an in vivo study in rabbit femur.
AB  - This study aimed at investigating if a coating of hydroxyapatite nanocrystals
      would enhance bone healing over time in trabecular bone. Sandblasted and acid
      etched titanium implants with and without a submicron thick coat of
      hydroxyapatite nanocrystals (nano-HA) were implanted in rabbit femur with healing
      times of 2, 4, and 9 weeks. Removal torque analyses and histological evaluations
      were performed. The torque analysis did not show any significant differences
      between the implants at any healing time. The control implant showed a tendency
      of more newly formed bone after 4 weeks of healing and significantly higher bone
      area values after 9 weeks of healing. According to the results from this present
      study, both control and nano-HA surfaces were biocompatible and osteoconductive.
      A submicron thick coating of hydroxyapatite nanocrystals deposited onto blasted
      and acid etched screw shaped titanium implants did not enhance bone healing, as
      compared to blasted and etched control implants when placed in trabecular bone. 

PMID- 24723953
TI  - Disease Management of Early Childhood Caries: ECC Collaborative Project.
AB  - Until recently, the standard of care for early childhood caries (ECC) has been
      primarily surgical and restorative treatment with little emphasis on preventing
      and managing the disease itself. It is now recognized that surgical treatment
      alone does not address the underlying etiology of the disease. Despite costly
      surgeries and reparative treatment, the onset and progression of caries are
      likely to continue. A successful rebalance of risk and protective factors may
      prevent, slow down, or even arrest dental caries and its progression. An 18-month
      risk-based chronic disease management (DM) approach to address ECC in preschool
      children was implemented as a quality improvement (QI) collaborative by seven
      teams of oral health care providers across the United States. In the aggregate,
      fewer DM children experienced new cavitation, pain, and referrals to the
      operating room (OR) for restorative treatment compared to baseline historical
      controls. The teams found that QI methods facilitated adoption of the DM approach
      and resulted in improved care to patients and better outcomes overall. Despite
      these successes, the wide scale adoption and spread of the DM approach may be
      limited unless health policy and payment reforms are enacted to compensate
      providers for implementing DM protocols in their practice. 

PMID- 24723954
TI  - Marginal and internal fit of cobalt-chromium fixed dental prostheses generated
      from digital and conventional impressions.
AB  - Objectives. Digital impressions are increasingly used and have the potential to
      avoid the problem of inaccurate impressions. Only a few studies to verify the
      accuracy of digital impressions have been performed. The purpose of this study
      was to compare the marginal and internal fit of 3-unit tooth supported fixed
      dental prostheses (FDPs) fabricated from digital and conventional impressions.
      Methods. Ten FDPs were produced from digital impressions using the iTero system
      and 10 FDPs were produced using vinyl polysiloxane (VPS) impression material. A
      triple-scan protocol and CAD software were used for measuring and calculating
      discrepancies of the FDPs at 3 standard areas: mean internal discrepancy,
      absolute marginal gap, and cervical area discrepancy. The Mann-Whitney U test was
      used for analyzing the results. Results. For conventional and digital
      impressions, respectively, FDPs had an absolute marginal gap of 147  MU m and 142
      MU m, cervical area discrepancy of 69  MU m and 44  MU m, and mean internal
      discrepancy of 117  MU m and 93  MU m. The differences were statistically
      significant in the cervical and internal areas (P < 0.001). Significance. The
      results indicated that the digital impression technique is more exact and can
      generate 3-unit FDPs with a significantly closer fit compared to the VPS
      technique. 

PMID- 24723955
TI  - Results of a Prospective Study of High-Dose or Conventional Anthracycline
      Cyclophosphamide Regimen Plus Radiotherapy for Localized Adult Non-Hodgkin's
      Primary Bone Lymphoma.
AB  - Background. Primary bone lymphoma (PBL) is a rare entity that has only been
      reviewed in one prospective and small retrospective studies, from which it is
      difficult to establish treatment guidelines. We prospectively evaluated high-dose
      or conventional anthracycline-cyclophosphamide dose and radiotherapy for PBL.
      Patients and Methods. The GOELAMS prospective multicenter study (1986-1998)
      enrolled adults with localized high-grade PBL according to age and performance
      status (PS). Patients <60 years received a high-dose CHOP regimen (VCAP) and
      those >=60 years a conventional anthracycline-cyclophosphamide regimen (VCEP
      bleomycin); all received intrathecal chemotherapy and local radiotherapy.
      Results. Among the 26 patients included (VCAP: 19; VCEP-bleomycin: 7), 39% had
      poor PS >=2. With a median follow-up of 8 years, overall survival, event-free
      survival, and relapse-free survival were 64%, 62%, and 65%, respectively, with no
      significant difference between treatment groups. Poor PS was significantly
      associated with shorter OS and EFS. Conclusions. Our results confirm the efficacy
      of our age-based therapeutic strategy. High-doses anthracycline-cyclophosphamide
      did not improve the outcome. VCEP-bleomycin is effective and well tolerated for
      old patients. The intensification must be considered for patients with PS >=2, a
      poor prognostic factor. 

PMID- 24723956
TI  - Use of autologous mesenchymal stem cells derived from bone marrow for the
      treatment of naturally injured spinal cord in dogs.
AB  - The use of stem cells in injury repair has been extensively investigated. Here,
      we examined the therapeutic effects of autologous bone marrow mesenchymal stem
      cells (MSC) transplantation in four dogs with natural traumatic spinal cord
      injuries. MSC were cultured in vitro, and proliferation rate and cell viability
      were evaluated. Cell suspensions were prepared and surgically administered into
      the spinal cord. The animals were clinically evaluated and examined by nuclear
      magnetic resonance. Ten days after the surgical procedure and MSC
      transplantation, we observed a progressive recovery of the panniculus reflex and
      diminished superficial and deep pain response, although there were still low
      proprioceptive reflexes in addition to a hyperreflex in the ataxic hind limb
      movement responses. Each dog demonstrated an improvement in these gains over
      time. Conscious reflex recovery occurred simultaneously with moderate improvement
      in intestine and urinary bladder functions in two of the four dogs. By the 18th
      month of clinical monitoring, we observed a remarkable clinical amelioration
      accompanied by improved movement, in three of the four dogs. However, no clinical
      gain was associated with alterations in magnetic resonance imaging. Our results
      indicate that MSC are potential candidates for the stem cell therapy following
      spinal cord injury. 

PMID- 24723957
TI  - Acupuncture for essential hypertension: a meta-analysis of randomized sham
      controlled clinical trials.
AB  - Background. Acupuncture is frequently advocated as an adjunct treatment for
      essential hypertension. The aim of this review was to assess its adjunct
      effectiveness in treating hypertension. Methods. We searched PubMed, the Cochrane
      Library, EMBASE, and the Chinese databases Sino-Med, CNKI, WanFang, and VIP
      through November, 2012, for eligible randomized controlled trials that compared
      acupuncture with sham acupuncture. Outcome measures were changes in diastolic
      (DBP) and systolic blood pressure (SBP). Results. A total of 4 randomized
      controlled trials were included. We found no evidence of an improvement with the
      fact that acupuncture relative to sham acupuncture in SBP change (n = 386; mean
      difference = -3.80 mmHg, 95% CI = -10.03-2.44 mmHg; I (2) = 99%), and an
      insignificant improvement in DBP change (n = 386; mean difference = -2.82 mmHg,
      95% CI = -5.22-(-0.43) mmHg; I (2) = 97%). In subgroup analyses, acupuncture
      significantly improved both SBP and DBP in patients taking antihypertensive
      medications. Only minor acupuncture-related adverse events were reported.
      Conclusions. Our results are consistent with acupuncture significantly lowers
      blood pressure in patients taking antihypertensive medications. We did not find
      that acupuncture without antihypertensive medications significantly improves
      blood pressure in those hypertensive patients. 

PMID- 24723958
TI  - Ganoderma lucidum Polysaccharides Reduce Lipopolysaccharide-Induced Interleukin-1
      beta Expression in Cultured Smooth Muscle Cells and in Thoracic Aortas in Mice.
AB  - The expression of inflammatory cytokines on vascular walls is a critical event in
      vascular diseases and inflammation. The aim of the present study was to examine
      the effects of an extract of Ganoderma lucidum (Reishi) polysaccharides (EORPs),
      which is effective against immunological disorders, on interleukin- (IL-) 1 beta
      expression by human aortic smooth muscle cells (HASMCs) and the underlying
      mechanism. The lipopolysaccharide- (LPS-) induced IL-1 beta expression was
      significantly reduced when HASMCs were pretreated with EORP by Western blot and
      immunofluorescent staining. Pretreatment with 10  MU g/mL EORP decreased LPS
      induced ERK, p38, JNK, and Akt phosphorylation. But the increase in IL-1 beta
      expression with LPS treatment was only inhibited by pretreatment with the ERK1/2
      inhibitor, while the JNK and p38 inhibitors had no effect. In addition, EORP
      reduced the phosphorylation and nuclear translocation of nuclear factor- (NF-)
      kappa B p65 in LPS-treated HASMCs. Furthermore, in vivo, IL-1 beta expression was
      strongly expressed in thoracic aortas in LPS-treated mice. Oral administration of
      EORP decreased IL-1 beta expression. The level of IL-1 beta expression in LPS
      treated or in LPS/EORP-treated group was very low and was similar to that of the
      saline-treated group in toll-like receptor 4-deficient (TLR4(-/-)) mice. These
      findings suggest that EORP has the anti-inflammatory property and could prove
      useful in the prevention of vascular diseases and inflammatory responses. 

PMID- 24723959
TI  - Anti-inflammatory effects of the chinese herbal formula sini tang in myocardial
      infarction rats.
AB  - The aim of this study was to evaluate the anti-inflammatory profiling of the
      Chinese herbal formula Sini Tang (SNT) in myocardial infarction (MI) rats. SNT, a
      decoction consisting of four herbs: Aconitum carmichaelii, Cinnamomum cassia,
      Zingiber officinale, and Glycyrrhiza uralensis, was characterized as a remedy to
      treat syndromes corresponding to heart failure and MI in China. Potential
      biomarkers, which reflect the extent of myocardial necrosis and correlate with
      cardiac outcomes following MI, such as atrial natriuretic peptide (ANP), high
      sensitivity C-reactive protein (hs-CRP), and proinflammatory cytokines such as
      tumor necrosis factor- alpha , interleukin-6, and interleukin-1 beta (TNF- alpha
      , IL-6, and IL-1 beta ) were determined in plasma, serum, and in myocardial
      tissue of MI rats after treatment with SNT. Our data indicate that SNT decreased
      significantly the levels of hs-CRP, TNF- alpha , IL-6, and IL-1 beta in MI rats.
      SNT decreased the expression of ANP levels in plasma and increased the vascular
      active marker nitric oxide, which limits vascular inflammation. In addition, SNT
      could decrease the expression of endothelin-1 levels in rat plasma post-MI. Our
      data suggest that the Chinese herbal formula SNT has the potential to improve
      cardiac function after MI. SNT may be a candidate for treating MI and its
      associated inflammatory responses. 

PMID- 24723961
TI  - Survival benefit of traditional chinese herbal medicine (a herbal formula for
      invigorating spleen) in gastric cancer patients with peritoneal metastasis.
AB  - Objective. We evaluated the efficiency of traditional Chinese herbal medicine (a
      compound herbal formula for invigorating spleen) as a complementary and
      alternative therapy for gastric cancer patients with peritoneal metastasis.
      Methods. Between 2001 and 2012, 93 gastric cancer patients with peritoneal
      metastasis were enrolled in this study. The effect of traditional Chinese herbal
      medicine on their long-term outcome was investigated. Kaplan-Meier method was
      used to assess the difference in survival time, and Cox proportional hazards
      regression analysis was performed to identify independent prognostic factors.
      Result. First-line palliative chemotherapy plus traditional Chinese herbal
      medicine was performed in 47 patients and the other 46 patients received
      chemotherapy alone. The overall survival was different between patients with and
      without traditional Chinese herbal medicine (12.0 versus 10.5 months; P = 0.046).
      According to the Cox proportional hazard model, first-line chemotherapy cycle
      (hazards ratio [HR] = 0.527; 95% CI = 0.323~0.860) and TCHM (hazards ratio [HR] =
      0.644; 95% CI = 0.481~0.992) were selected as independent prognostic factors for
      survival. Conclusion. The results suggest that traditional Chinese herbal
      medicine could improve the prognosis of the gastric cancer patients with
      peritoneal metastasis. 

PMID- 24723960
TI  - Oral Administration of MBG to Modulate Immune Responses and Suppress OVA
      Sensitized Allergy in a Murine Model.
AB  - Recently studies performed on mushroom isolated polysaccharides demonstrated that
      beta -(1,3)-glucan may affect the balance of Th1/Th2 cell response. Using
      ovalbumin (OVA) as a hypersensitivity inducer, we evaluated the ability of
      mushroom beta-glucan (MBG) in modulating Th1/Th2 cell responses in B6 mice. As
      compared to the control group, administration of MBG resulted in an increase of
      phagocytic activities, Th1 cytokine productions, immunoglobulins including IgG2A
      and IgA, and a significant expression of the splenic surface markers including
      CD3, CD4, CD8, and F4/80. In contrast, administration of MBG has significantly
      suppressed IgE and IgG1 levels and Th2 cytokines including IL-4, IL-5, and IL-6.
      Histopathological observation of MBG-treated followed by OVA-treated mice showed
      less filtration of eosinophil in pulmonary tissue sections. Our data suggested
      that administration of MBG treatments alters the natural course of the IgE
      mediated hypersensitivities. In this investigation, we realize the mushroom beta
      glucan alter the Th2 response toward the Th1 in the allergic, resulting in a
      reduction in IgE productions which played a substantive role in reducing the
      severity of IgE-mediated hypersensitivity. 

PMID- 24723962
TI  - Synergistic Effect of Zuo Jin Wan on DDP-Induced Apoptosis in Human Gastric
      Cancer SGC-7901/DDP Cells.
AB  - A traditional Chinese medicine (TCM) formula, Zuo Jin Wan (ZJW), has been found
      as an anticancer drug in human cancer. In this study, we investigated the
      synergistic effect of ZJW extracts on DDP-induced apoptosis in human gastric
      cancer SGC-7901/DDP cells. Our results demonstrated that ZJW extracts could
      increase the sensitivity of SGC-7901/DDP cells to DDP by increasing the
      concentration of DDP in cytoplasm and enhance the proapoptosis of DDP by
      upregulating the JNK and Bax expression, downregulating the Bcl-2 expression,
      increasing the accumulation of Cytochrome C in cytoplasm, and promoting the
      activities of caspase-3 and caspase-9. In vivo, ZJW extracts enhanced the
      inhibiting effect of DDP on tumor growth in SGC-7901/DDP xenograft model and
      upregulated the expression of p-JNK and Bax but downregulated the Bcl-2
      expression in xenograft tumors. In conclusion, in vitro and in vivo, ZJW extracts
      could enhance the proapoptotic effect of DDP by promoting the activation of JNK
      and the expression of Bcl-2, inhibiting the Bax expression, followed by
      increasing the release of Cytochrome C from mitochondria to cytoplasm, and
      finally activating the caspase cade reaction. Our results implied that ZJW might
      serve as a synergistic drug with chemotherapeutic drugs DDP in the treatment of
      gastric cancer. 

PMID- 24723963
TI  - Randomized, Double-Blind Clinical Trial to Assess the Acute Diuretic Effect of
      Equisetum arvense (Field Horsetail) in Healthy Volunteers.
AB  - In this double-blind, randomized clinical trial, 36 healthy male volunteers were
      randomly distributed into three groups (n = 12) that underwent a three-step
      treatment. For four consecutive days, we alternately administered a standardized
      dried extract of Equisetum arvense (EADE, 900 mg/day), placebo (corn starch, 900
      mg/day), or hydrochlorothiazide (25 mg/day), separated by a 10-day washout
      period. Each volunteer served as his own control, and the groups' results were
      compared. We repeated the same evaluation after each stage of treatment to
      evaluate the safety of the drug. The diuretic effect of EADE was assessed by
      monitoring the volunteers' water balance over a 24 h period. The E. arvense
      extract produced a diuretic effect that was stronger than that of the negative
      control and was equivalent to that of hydrochlorothiazide without causing
      significant changes in the elimination of electrolytes. There was no significant
      increase in the urinary elimination of catabolites. Rare minor adverse events
      were reported. The clinical examinations and laboratory tests showed no changes
      before or after the experiment, suggesting that the drug is safe for acute use.
      Further research is needed to better clarify the mechanism of diuretic action and
      the other possible pharmacological actions of this phytomedicine. 

PMID- 24723964
TI  - Immunomodulatory activity of complementary and alternative medicines.

PMID- 24723965
TI  - The effects of maekmoondong-tang on cockroach extract-induced allergic asthma.
AB  - Maekmoondong-tang (MMDT) has long been used in Asian countries to treat
      respiratory diseases. However, the precise mechanisms underlying its effects on
      asthma are unknown. This study was conducted to evaluate the protective effects
      of MMDT in a cockroach allergen (CKA-)induced animal model of allergic asthma.
      After being challenged with CKA, the number of macrophages, eosinophils,
      neutrophils, lymphocytes, and total cells in the bronchoalveolar lavage fluid
      (BALF) was evaluated. The Th2 specific cytokines IL-4, IL-5, and IL-13 were also
      analyzed in BALF along with IgE levels in serum. For histological analysis,
      hematoxylin and eosin (H&E) staining, periodic acid-Schiff (PAS) staining, and
      immunohistochemical staining were performed. In addition, airway
      hyperresponsiveness was assessed by noninvasive plethysmography. The cellular
      profiles and histopathologic analysis demonstrated that peribronchial and
      perivascular inflammatory cell infiltrates were significantly decreased in the
      MMDT-treated groups compared with the cockroach extract-injected (CKA) groups. In
      addition, the IgE, IL-4, IL-5, and IL-13 levels were significantly decreased in
      the MMDT group. MMDT treatment also significantly attenuated airway
      hyperresponsiveness. These results demonstrated that MMDT significantly reduced
      the hallmark signs of asthma: elevated serum IgE, airway eosinophilia, airway
      remodeling, mucus hypersecretion, and airway hyperresponsiveness. The remarkable
      antiasthmatic effects of MMDT suggest its therapeutic potential in allergic
      asthma treatment. 

PMID- 24723966
TI  - Pregnancy monitoring.

PMID- 24723967
TI  - An SIRS epidemic model incorporating media coverage with time delay.
AB  - An SIRS epidemic model incorporating media coverage with time delay is proposed.
      The positivity and boundedness are studied firstly. The locally asymptotical
      stability of the disease-free equilibrium and endemic equilibrium is studied in
      succession. And then, the conditions on which periodic orbits bifurcate are
      given. Furthermore, we show that the local Hopf bifurcation implies the global
      Hopf bifurcation after the second critical value of the delay. The obtained
      results show that the time delay in media coverage can not affect the stability
      of the disease-free equilibrium when the basic reproduction number R 0 < 1.
      However, when R 0 > 1, the stability of the endemic equilibrium will be affected
      by the time delay; there will be a family of periodic orbits bifurcating from the
      endemic equilibrium when the time delay increases through a critical value.
      Finally, some examples for numerical simulations are also included. 

PMID- 24723969
TI  - Efficacy of lenalidomide in association with cyclophosphamide and dexamethasone
      in multiple myeloma patient with bilateral retro-orbital localisation.
AB  - Extramedullary localisation is an uncommon manifestation in multiple myeloma
      (MM). Ocular involvement is rare. Here, we describe a relapse of MM with
      bilateral retro-orbital localisation without any bone involvement with good and
      rapid response to therapy with lenalidomide, dexamethasone, and cyclophosphamide.

PMID- 24723968
TI  - First comprehensive in silico analysis of the functional and structural
      consequences of SNPs in human GalNAc-T1 gene.
AB  - GalNAc-T1, a key candidate of GalNac-transferases genes family that is involved
      in mucin-type O-linked glycosylation pathway, is expressed in most biological
      tissues and cell types. Despite the reported association of GalNAc-T1 gene
      mutations with human disease susceptibility, the comprehensive computational
      analysis of coding, noncoding and regulatory SNPs, and their functional impacts
      on protein level, still remains unknown. Therefore, sequence- and structure-based
      computational tools were employed to screen the entire listed coding SNPs of
      GalNAc-T1 gene in order to identify and characterize them. Our concordant in
      silico analysis by SIFT, PolyPhen-2, PANTHER-cSNP, and SNPeffect tools,
      identified the potential nsSNPs (S143P, G258V, and Y414D variants) from 18 nsSNPs
      of GalNAc-T1. Additionally, 2 regulatory SNPs (rs72964406 and #x26; rs34304568)
      were also identified in GalNAc-T1 by using FastSNP tool. Using multiple
      computational approaches, we have systematically classified the functional
      mutations in regulatory and coding regions that can modify expression and
      function of GalNAc-T1 enzyme. These genetic variants can further assist in better
      understanding the wide range of disease susceptibility associated with the mucin
      based cell signalling and pathogenic binding, and may help to develop novel
      therapeutic elements for associated diseases. 

PMID- 24723970
TI  - Primary breast lymphoma in males-a report of two cases with a review of the
      literature.
AB  - Primary breast lymphoma (PBL) in males is a rare clinical entity and has been
      reported in anecdotal case reports up until now. We report two cases of PBL from
      a tertiary care centre in Southern India. A 46-year-old male presented with a
      lump in the right breast with right axillary lymphadenopathy; a biopsy with
      immunohistochemistry showed neoplastic cells positive for CD 20 and negative for
      CD 30, epithelial membrane antigen, anaplastic lymphoma kinase, suggestive of
      diffuse large B cell lymphoma stage IIEA. He received three cycles of CHOP
      (cyclophosphamide, adriamycin, vincristine, and prednisolone) chemotherapy, then
      developed a cerebrovascular accident, and died. The other patient was a 60-year
      old male with a left breast lump with left axillary lymphadenopathy. The biopsy
      with immunohistochemistry showed neoplastic cells positive for CD 23 and CD 5,
      suggestive of small lymphocytic lymphoma stage IIEA. Initially he received three
      cycles of cyclophosphamide, vincristine, and prednisolone (COP) and defaulted.
      One year later, he received six cycles of COP chemotherapy, developed progressive
      disease, and was lost to follow-up. The literature on PBL in males was reviewed.
      To conclude, PBL in males is an extremely rare disease and can mimic breast
      cancer. A strong index of suspicion with early diagnosis by biopsy with
      immunohistochemistry and treatment with rituximab- and anthracycline-based
      chemotherapy followed by radiotherapy will improve overall survival. 

PMID- 24723971
TI  - Immune cell infiltration patterns and survival in head and neck squamous cell
      carcinoma.
AB  - PURPOSE: This study examines the tumour-host immune interactions in head and neck
      squamous cell carcinoma (HNSCC) and their relationship to human papillomavirus
      (HPV) infectivity and patient survival. METHODS: The adaptive and innate immune
      profile of surgical tumour specimens obtained from HNSCC patients was determined
      using qRT-PCR and immunohistochemistry. Intratumoural and invading margin
      leukocyte populations (CD3, CD8, CD16, CD20, CD68, FoxP3 and HLA-DR) were
      quantified and compared with patient disease-specific survival. Additionally, the
      expression of 41 immune activation- and suppression-related genes was evaluated
      in the tumour microenvironment. Tumour cells were also assessed for expression of
      HLA-A, HLA-G and HLA-DR. HPV infectivity of tumour biopsies was determined using
      HPV consensus primers (MY09/MY11 and GP5+/GP6+) and confirmed with p16
      immunohistochemistry. RESULTS: HPV+ patient samples showed a significantly
      increased infiltration by intratumoural CD20+ B cells, as well as by invasive
      margin FoxP3+Treg, compared with HPV- patient samples. There was also a trend
      towards increased intratumoural CD8+ T cells and HLA-G expression on tumour cells
      in HPV+ samples. qRT-PCR data demonstrated a general pattern of increased immune
      activation and suppression mechanisms in HPV+ samples. Additionally, a combined
      score of intratumoural and invasive margin FoxP3 infiltration was significantly
      associated with disease-specific survival (P < 0.05). CONCLUSIONS: These data
      demonstrate significant differences in the immune cell profile of HPV+ and HPV-
      HNSCC. This study identifies several possible targets for immunotherapy and
      possible prognostic markers (FoxP3 and HLA-G) that may be specific to HNSCC.

PMID- 24723973
TI  - The "cavitary" type of angiogenesis by gastric cancer. Morphological
      characteristics and prognostic value.
AB  - The "cavitary" type of angiogenesis in patients with gastric cancer (GC) is
      described for the first time. MATERIAL AND METHODS: The samples of tumour and
      adjacent gastric mucosa (GM) in 73 patients with GC who had undergone radical
      surgery were being studied. The sections were stained with hematoxylin and eosin
      (H&E) and immunohistochemically (IGH) using antibodies to CD34. RESULTS: A new
      type of vessel formation consists of the appearance of cavitary structures (CS)
      in tumours and the adjacent GM, which are then lined by endothelial cells and
      merged into the blood vessels of the organ. We believe that the CS can be formed
      by means: 1) of the abruption of layers of epithelial cells (both normal and
      tumoral) from their underlying foundation and their desquamation into the lumen
      of the "obliterated" gastric glands (GG); 2) of the dilatation of the GG and
      thinning of their walls; 3) of the formation of "cavity" directly in the lamina
      propria of GM or in the tumoral stroma. It was noted that only the presence of
      multiple "cavitary" vessels (CV) of type-1 had been associated with the decrease
      of 3-year overall survival (OR=15,0, 95%CI=2,96-76,31) and relapse-free survival
      (OR=14,93, 95%CI=4,34-51,38). We also observed the improvement of the long-term
      outcomes in patients with GC having received antibacterial therapy (AT) before
      surgery that can be associated with its influence on the formation of CV type-1.
      CONCLUSION: The described new type of angiogenesis is of great clinical
      importance.

PMID- 24723972
TI  - Investigating molecular profiles of ovarian cancer: an update on cancer stem
      cells.
AB  - Currently we are more and more improving our knowledge about the characteristics
      and the role of cancer stem cells in human cancer. Particularly we have realized
      that self-renewing ovarian cancer stem cells (CSCs) or ovarian cancer-initiating
      cells, and mesenchymal stem cells (SCs) too, are probably implicated in the
      etiopathogenesis of epithelial ovarian cancer (EOC). There is clear evidence that
      these cells are also involved in its intra- and extra-peritoneal diffusion and in
      the occurrence of chemo-resistance. In assessing the molecular characteristics of
      ovarian CSCs, we have to take note that these cellular populations are rare and
      the absence of specific cell surface markers represents a challenge to isolate
      and identify pure SC populations. In our review, we focused our attention on the
      molecular characteristics of epithelial ovarian CSCs and on the methods to detect
      them starting from their biological features. The study of ovarian CSCs is taking
      on an increasingly important strategic role, mostly for the potential therapeutic
      application in the next future. 

PMID- 24723974
TI  - Eribulin mesylate in pretreated breast cancer patients: a multicenter
      retrospective observational study.
AB  - BACKGROUND: Eribulin was recently approved in patients progressing after being
      treated with anthracyclines and taxanes and after two or more chemotherapy lines
      for advanced disease. OBJECTIVES: This multicenter observational retrospective
      study was performed in order to evaluate activity and tolerability of eribulin in
      real-world patient population. METHODS: 133 advanced breast cancer patients
      pretreated with >= 2 chemotherapy lines for metastatic disease were
      retrospectively enrolled in the observational trial in 11 italian cancer centres.
      RESULTS: A median of 5 cycles of eribulin (range, 1-15) were administered. Twenty
      eight partial responses were observed, for an overall response rate of 21.1%
      (95%CI,14.1-28.0). A stable disease was recorded in 57 patients (42.8%), and a
      clinical benefit (response or stable disease lasting >= six months) was observed
      in 51 patients (38.3%, 95%CI, 30.1-46.6). The subgroup analysis showed that a
      significant improvement in term of partial response and clinical benefit was
      achieved when eribulin was administered in HER-2 negative tumors (p=0.01 and
      p=0.004, respectively) and when it is given as third-line (p=0.09 and p=0.02,
      respectively). Toxicity was manageable; fatigue is the most common side effect
      observed, usually of low-grade, and clearly cumulative-dose related. CONCLUSIONS:
      In this retrospective, observational analysis eribulin confirmed its efficacy and
      manageable tolerability even in real-world population and in heavily pretreated
      patients.

PMID- 24723975
TI  - Differentiation of Benign Fluid Collections from Soft-Tissue Sarcomas on FDG
      PET/CT.
AB  - OBJECTIVE: To assess the diagnostic performance of (18)F-FDG PET-CT in
      differentiating soft tissue sarcomas (STSs) from benign fluid collections (BFs).
      MATERIALS AND METHODS: Four readers independently reviewed 100 lesions on (18)F
      FDG PET-CT and subjectively classified each lesion as an STS or BF and scored the
      spatial pattern of (18)F-FDG avidity (SP) of each on a 4-point ordered scale
      (thin, moderate, thick, solid). RESULTS: Subjective assessment by readers allowed
      sensitive (91%-98%) differentiation of STSs from BFs, with lower specificity (59%
      91%). The STSs had significantly higher SUVmax (median 10.7, range: 2.0-33.7)
      than BFs (median 2.8, range: 1.1-12.3). Reader agreement in assessment of SP had
      average kappa = 0.61 (range 0.46-0.70). Classification of thick or solid SP as
      STS yielded an inter-reader averaged sensitivity and specificity of 69% and 98%,
      respectively. The presence of thick or solid SP resulted in 14.1-fold increase in
      partial odds of STS. Each unit increase in SUVmax resulted in 1.35-fold increase
      in partial odds of STS. The receiver operating characteristic (ROC) curves and
      95% intervals for SUVmax alone and SUVmax + SP overlapped. The average subjective
      assessments for the four readers and estimated performance of using SP alone were
      both contained within the 95% intervals of the two ROC curves. CONCLUSIONS: (18)F
      FDG PET-CT is a sensitive modality for differentiating STSs from BFs. SUVmax and
      SP are significantly associated with STS. Classification schemes based upon
      SUVmax alone or augmented with SP can be useful for distinguishing STS from BF.

PMID- 24723976
TI  - Identification of a Novel Compound That Suppresses Breast Cancer Invasiveness by
      Inhibiting Transforming Growth Factor-beta Signaling via Estrogen Receptor alpha.
AB  - Breast cancer is the most frequently diagnosed cancer and the leading cause of
      death by cancer among females worldwide. An overwhelming majority of these deaths
      is because of metastasis. Estrogen stimulates and promotes growth of breast
      tumors, whereas transforming growth factor-beta (TGF-beta) signaling promotes
      invasion and metastasis. We previously reported that estrogen and estrogen
      receptor alpha (ERalpha) suppressed breast cancer metastasis by inhibiting TGF
      beta signaling, whereas antiestrogens that suppress breast cancer growth, such as
      the selective ER modulator tamoxifen (TAM) or the pure antiestrogen fulvestrant
      (ICI 182,780), cannot suppress TGF-beta signaling or breast cancer invasiveness.
      Therefore, we predicted that a compound that inhibits TGF-beta signaling but does
      not facilitate ERalpha signaling would be ideal for suppressing breast cancer
      invasiveness and growth. In the present study, we identified an ideal candidate
      compound, N-23. Like estrogen, N-23 strongly decreased expression of TGF
      beta/Smad target gene plasminogen activator inhibitor-1 (PAI-1), but it did not
      increase the expression of ERalpha target gene pS2. While estrogen decreased the
      levels of phosphorylated Smad2 and Smad3, N-23 had no effect. In addition, TGF
      beta-dependent recruitment of Smad3 to the PAI-1 gene promoter was inhibited in
      the presence of estrogen or N-23. We also investigated the effects of N-23 on
      proliferation, migration, and invasion of breast cancer cells. In contrast to
      estrogen, N-23 inhibited the cellular proliferation of breast cancer cells.
      Moreover, we showed that N-23 suppressed the migration and invasion of breast
      cancer cells to the same extent as by estrogen. Taken together, our findings
      indicate that N-23 may be a candidate compound that is effective in inhibiting
      breast cancer progression. 

PMID- 24723977
TI  - Enhancement of Aerosol Cisplatin Chemotherapy with Gene Therapy Expressing ABC10
      protein in Respiratory System.
AB  - Inhaled therapy for lung cancer is a local form of treatment. Currently inhaled
      non-specific cytotoxic agents have been evaluated as a future treatment for local
      disease control and distant metastasis control. There are few information
      regarding the influence of local transporters and gene expression of the
      respiratory epithelium to the absorption of administered drugs. In the current
      work we used adenoviral-type 5(dE1/E3) (Cytomegalovirus promoter) with human
      ABCA10 transgene (Ad-h-ABCA10) purchased from Vector Labs((r)) in order to
      investigate whether gene therapy can be used as a pre-treatment to enhance the
      efficiency of inhaled cisplatin. We included the following groups to our work: a)
      control, b) aerosol vector, c) aerosol vector plus cisplatin, d) aerosol
      cisplatin, e) intratumoral cisplatin administration, f) intratumoral vector plus
      cisplatin administration. The results indicate that the aerosol cisplatin group
      had a long term survival with the intratumoral cisplatin group following. The
      enhancement of the ABCA family locally to the respiratory system prior to the
      aerosol cisplatin administration can be used safely and efficiently. Future
      treatment design of local therapies should include the investigation of local
      transporters and genes. 

PMID- 24723978
TI  - Phase I and II Study of Gemcitabine and Vinorelbine in Heavily Pretreated
      Patients with Metastatic Breast Cancer and Review of the Literature.
AB  - BACKGROUND: Many phase II trials investigated the combination of Gemcitabine (G)
      and Vinorelbine (V) in the treatment of metastatic breast cancer (MBC) with
      variable outcomes. This study was conducted to explore whether this combination
      was effective and tolerable in MBC patients who were heavily pretreated with
      anthracyclines and taxanes. METHODS: A phase I study was conducted first to
      establish the maximum tolerated dose (MTD) of the G and V combination in MBC
      patients. Then, a phase II study evaluated the response rates, the median time to
      progression (TTP), the overall survival (OS) as well as the toxicities resulting
      from this combination at the MTD. RESULTS: Nine patients were enrolled in the
      phase I study. The MTD was identified as 700mg/m(2) of G on days 1 and 8 in
      combination with 15 mg/m(2) of V on days 2 and 9, every 21 days. Twenty-one of 25
      patients involved in the phase II study were evaluable for response. No complete
      or partial responses were achieved; 6 patients (24.0%) had stable disease and 15
      (60.0%) progressed. The median TTP was 2 months and the median OS 10 months.
      Grade 3/4 Neutropenia was the major hematologic toxicity, occurring in 52% of the
      cycles. The most common non-hematologic grade 3/4 toxicities were fatigue (18%),
      myalgias (17%) and arthralgias (13%). CONCLUSION: In heavily pretreated patients
      with MBC, the combination of G and V at the doses stated above was ineffective as
      it did not induce partial or complete responses. Other chemotherapy agents or
      combinations should be evaluated in future studies.

PMID- 24723979
TI  - Anti-angiogenesis therapy in the Vx2 rabbit cancer model with a lipase-cleavable
      Sn 2 taxane phospholipid prodrug using alpha(v)beta3-targeted theranostic
      nanoparticles.
AB  - In nanomedicine, the hydrophobic nature of paclitaxel has favored its
      incorporation into many nanoparticle formulations for anti-cancer chemotherapy.
      At lower doses taxanes are reported to elicit anti-angiogenic responses. In the
      present study, the facile synthesis, development and characterization of a new
      lipase-labile docetaxel prodrug is reported and shown to be an effective anti
      angiogenic agent in vitro and in vivo. The Sn 2 phosphatidylcholine prodrug was
      stably incorporated into the lipid membrane of alpha(v)beta3-integrin targeted
      perfluorocarbon (PFC) nanoparticles (alpha(v)beta3-Dxtl-PD NP) and did not
      appreciably release during dissolution against PBS buffer or plasma over three
      days. Overnight exposure of alpha(v)beta3-Dxtl-PD NP to plasma spiked with
      phospholipase enzyme failed to liberate the taxane from the membrane until the
      nanoparticle integrity was compromised with alcohol. The bioactivity and efficacy
      of alpha(v)beta3-Dxtl-PD NP in endothelial cell culture was as effective as
      Taxol((r)) or free docetaxel in methanol at equimolar doses over 96 hours. The
      anti-angiogenesis effectiveness of alpha(v)beta3-Dxtl-PD NP was demonstrated in
      the Vx2 rabbit model using MR imaging of angiogenesis with the same alpha(v)beta3
      PFC nanoparticle platform. Nontargeted Dxtl-PD NP had a similar MR anti
      angiogenesis response as the integrin-targeted agent, but microscopically
      measured decreases in tumor cell proliferation and increased apoptosis were
      detected only for the targeted drug. Equivalent dosages of Abraxane((r)) given
      over the same treatment schedule had no effect on angiogenesis when compared to
      control rabbits receiving saline only. These data demonstrate that alpha(v)beta3
      Dxtl-PD NP can reduce MR detectable angiogenesis and slow tumor progression in
      the Vx2 model, whereas equivalent systemic treatment with free taxane had no
      benefit.

PMID- 24723980
TI  - Polysaccharide nanosystems for future progress in cardiovascular pathologies.
AB  - Natural polysaccharides have received a lot of attention in the biomedical field.
      Indeed, sources of polysaccharides, extracted or produced from plants, bacteria,
      fungi or algae, are diverse and renewable. Moreover, recent progresses in
      polysaccharide chemistry and nanotechnologies allow elaborating new dedicated
      nanosystems. Polysaccharide-based nanosystems may be designed for interacting in
      several biological processes. In particular, the atherothrombotic pathology is
      highly concerned by polysaccharide-mediated recognition. Atherothrombotic
      diseases, regardless of the anatomical localization, remain the main causes of
      morbidity and mortality in the industrialized world. This review intends to
      provide an overview on polysaccharide-based nanosystems as drug delivery systems
      and targeted contrast agents for molecular imaging with an emphasis on the
      treatment and imaging of cardiovascular pathologies. 

PMID- 24723982
TI  - Real-time assessment of tissue hypoxia in vivo with combined photoacoustics and
      high-frequency ultrasound.
AB  - PURPOSE: In preclinical cancer studies, non-invasive functional imaging has
      become an important tool to assess tumor development and therapeutic effects.
      Tumor hypoxia is closely associated with tumor aggressiveness and is therefore a
      key parameter to be monitored. Recently, photoacoustic (PA) imaging with
      inherently co-registered high-frequency ultrasound (US) has reached preclinical
      applicability, allowing parallel collection of anatomical and functional
      information. Dual-wavelength PA imaging can be used to quantify tissue oxygen
      saturation based on the absorbance spectrum differences between hemoglobin and
      deoxyhemoglobin. EXPERIMENTAL DESIGN: A new bi-modal PA/US system for small
      animal imaging was employed to test feasibility and reliability of dual
      wavelength PA for measuring relative tissue oxygenation. Murine models of
      pancreatic and colon cancer were imaged, and differences in tissue oxygenation
      were compared to immunohistochemistry for hypoxia in the corresponding tissue
      regions. RESULTS: Functional studies proved feasibility and reliability of
      oxygenation detection in murine tissue in vivo. Tumor models exhibited different
      levels of hypoxia in localized regions, which positively correlated with
      immunohistochemical staining for hypoxia. Contrast-enhanced imaging yielded
      complementary information on tissue perfusion using the same system. CONCLUSION:
      Bimodal PA/US imaging can be utilized to reliably detect hypoxic tumor regions in
      murine tumor models, thus providing the possibility to collect anatomical and
      functional information on tumor growth and treatment response live in
      longitudinal preclinical studies.

PMID- 24723981
TI  - Abdominal aortic aneurysms targeted by functionalized polysaccharide
      microparticles: a new tool for SPECT imaging.
AB  - Aneurysm diagnostic is nowadays limited by the lack of technology that enables
      early detection and rupture risk prediction. New non invasive tools for molecular
      imaging are still required. In the present study, we present an innovative SPECT
      diagnostic tool for abdominal aortic aneurysm (AAA) produced from injectable
      polysaccharide microparticles radiolabeled with technetium 99m ((99m)Tc) and
      functionalized with fucoidan, a sulfated polysaccharide with the ability to
      target P-Selectin. P-Selectin is a cell adhesion molecule expressed on activated
      endothelial cells and platelets which can be found in the thrombus of aneurysms,
      as well as in other vascular pathologies. Microparticles with a maximum
      hydrodynamic diameter of 4 um were obtained by crosslinking the polysaccharides
      dextran and pullulan. They were functionalized with fucoidan. In vitro
      interactions with human activated platelets were assessed by flow cytometry that
      demonstrated a specific affinity of fucoidan functionalized microparticles for P
      Selectin expressed by activated platelets. For in vivo AAA imaging,
      microparticles were radiolabeled with (99m)Tc and intravenously injected into
      healthy and AAA rats obtained by elastase perfusion through the aorta wall.
      Animals were scanned by SPECT imaging. A strong contrast enhancement located in
      the abdominal aorta of AAA rats was obtained, while no signal was obtained in
      healthy rats or in AAA rats after injection of non-functionalized control
      microparticles. Histological studies revealed that functionalized radiolabeled
      polysaccharide microparticles were localized in the AAA wall, in the same
      location where P-Selectin was expressed. These microparticles therefore
      constitute a promising SPECT imaging tool for AAA and potentially for other
      vascular diseases characterized by P-Selectin expression. Future work will focus
      on validating the efficiency of the microparticles to diagnose these other
      pathologies and the different stages of AAA. Incorporation of a therapeutic
      molecule is also considered. 

PMID- 24723983
TI  - Polyacrylamide-based biocompatible Nanoplatform enhances the tumor uptake,
      PET/fluorescence imaging and anticancer activity of a chlorophyll analog.
AB  - In this report we demonstrate the outstanding advantages of multifunctional
      nanoplatforms for cancer-imaging and therapy. The non-toxic polyacrylamide (PAA)
      nanoparticles (size:18-25 nm) formulation drastically changed the pharmacokinetic
      profile of the 124I- labeled chlorophyll-a derivative (formulated in 10% ethanol
      in PBS) with a remarkable enhancement in tumor uptake, and significantly reduced
      uptake in spleen and liver. Among the various nanoformulations investigated, the
      124I- labeled photosensitizer (dose: 0.6142 MBq), and the cyanine dye
      nanoparticles (CD-NP) conjugate (dose 0.3 MUmol/kg) in combination showed great
      potential for tumor imaging (PET/NIR fluorescence) in BALB/c mice bearing Colon26
      tumors. Compared to free non-labeled photosensitizer, the corresponding PAA
      nanoformulation under similar treatment parameters showed a remarkable
      enhancement in long-term tumor cure by PDT (photodynamic therapy) and provides an
      opportunity to develop a single nanoplatform for tumor-imaging (PET/fluorescence)
      and phototherapy, a practical "See and Treat" approach.

PMID- 24723984
TI  - Polyglycerolsulfate functionalized gold nanorods as optoacoustic signal
      nanoamplifiers for in vivo bioimaging of rheumatoid arthritis.
AB  - We have synthesized a targeted imaging agent for rheumatoid arthritis based on
      polysulfated gold nanorods. The CTAB layer on gold nanorods was first replaced
      with PEG-thiol and then with dendritic polyglycerolsulfate at elevated
      temperature, which resulted in significantly reduced cytotoxicity compared to
      polyanionic gold nanorods functionalized by non-covalent approaches. In addition
      to classical characterization methods, we have established a facile UV-VIS based
      BaCl2 agglomeration assay to confirm a quantitative removal of unbound ligand.
      With the help of a competitive surface plasmon resonance-based L-selectin binding
      assay and a leukocyte adhesion-based flow cell assay, we have demonstrated the
      high inflammation targeting potential of the synthesized gold nanorods in vitro.
      In combination with the surface plasmon resonance band of AuNRs at 780 nm, these
      findings permitted the imaging of inflammation in an in vivo mouse model for
      rheumatoid arthritis with high contrast using multispectral optoacoustic
      tomography. The study offers a robust method for otherwise difficult to obtain
      covalently functionalized polyanionic gold nanorods, which are suitable for
      biological applications as well as a low-cost, actively targeted, and high
      contrast imaging agent for the diagnosis of rheumatoid arthritis. This paves the
      way for further research in other inflammation associated pathologies, in
      particular, when photothermal therapy can be applied. 

PMID- 24723985
TI  - A novel tumor targeting drug carrier for optical imaging and therapy.
AB  - Human serum albumin (HSA), a naturally abundant protein in blood plasma and
      tissue fluids, has an extraordinary ligand-binding capacity and is advocated as a
      drug carrier to facilitate drug delivery. To render it tumor targeting
      specificity, we generated a recombinant HSA fused with the amino-terminal
      fragment (ATF) of urokinase, allowing the fusion protein to bind to urokinase
      receptor (uPAR), which is shown to have a high expression level in many tumors,
      but not in normal tissues. To test the efficacy of this bifunctional protein (ATF
      HSA), a hydrophobic photosensitizer (mono-substituted beta-carboxy phthalocyanine
      zinc, CPZ) was chosen as a cytotoxic agent. A dilution-incubation-purification
      (DIP) strategy was developed to load the ATF-HSA with this CPZ, forming a 1:1
      molecular complex (ATF-HSA:CPZ). We demonstrated that CPZ was indeed embedded
      inside ATF-HSA at the fatty acid binding site 1 (FA1) of HSA, giving a
      hydrodynamic radius of 7.5 nm, close to HSA's (6.5 nm). ATF-HSA:CPZ showed high
      stability and remarkable optical and photophysical properties in aqueous
      solution. In addition, the molecular complex ATF-HSA:CPZ can bind to recombinant
      uPAR in vitro and uPAR on tumor cell surfaces, and was efficient in photodynamic
      killing of tumor cells. The tumor-killing potency of this molecular complex was
      further demonstrated in a tumor-bearing mouse model at a dose of 0.080 MUmol /
      kg, or 0.050 mg CPZ / kg of mouse body weight. Using fluorescent molecular
      tomography (FMT), ATF-HSA:CPZ was shown to accumulate specifically in tumors, and
      importantly, such tumor retention was higher than that of HSA:CPZ. Together,
      these results indicate that ATF-HSA:CPZ is not only an efficient tumor-specific
      cytotoxic agent, but also an useful tumor-specific imaging probe. This
      bifunctional protein ATF-HSA can also be used as a drug carrier for other types
      of cytotoxic or imaging agents to render them specificity for uPAR-expressing
      tumors. 

PMID- 24723987
TI  - Preserving Differential Privacy in Degree-Correlation based Graph Generation.
AB  - Enabling accurate analysis of social network data while preserving differential
      privacy has been challenging since graph features such as cluster coefficient
      often have high sensitivity, which is different from traditional aggregate
      functions (e.g., count and sum) on tabular data. In this paper, we study the
      problem of enforcing edge differential privacy in graph generation. The idea is
      to enforce differential privacy on graph model parameters learned from the
      original network and then generate the graphs for releasing using the graph model
      with the private parameters. In particular, we develop a differential privacy
      preserving graph generator based on the dK-graph generation model. We first
      derive from the original graph various parameters (i.e., degree correlations)
      used in the dK-graph model, then enforce edge differential privacy on the learned
      parameters, and finally use the dK-graph model with the perturbed parameters to
      generate graphs. For the 2K-graph model, we enforce the edge differential privacy
      by calibrating noise based on the smooth sensitivity, rather than the global
      sensitivity. By doing this, we achieve the strict differential privacy guarantee
      with smaller magnitude noise. We conduct experiments on four real networks and
      compare the performance of our private dK-graph models with the stochastic
      Kronecker graph generation model in terms of utility and privacy tradeoff.
      Empirical evaluations show the developed private dK-graph generation models
      significantly outperform the approach based on the stochastic Kronecker
      generation model.

PMID- 24723988
TI  - Contrast-enhanced ultrasonography for the determination of Crohn's disease
      activity - preliminary experience.
AB  - BACKGROUND: Contrast-enhanced ultrasound (CEUS) is a recent non-invasive
      modality, which may partially replace currently used techniques (endoscopy, CT
      enterography and MR enterography) in the diagnostics and assessment of Crohn's
      disease (CD). The aim of the study was to analyze early experience in the use of
      CEUS for the measurement of activity and staging of CD. MATERIAL/METHODS: Eleven
      patients previously diagnosed with CD were included in the study. They underwent
      contrast-enhanced ultrasonography (SonoVue, Bracco), low-dose CT enterography
      (LDCTE), assessment of laboratory markers of inflammation and clinical CD
      activity index (CDAI). Contrast enhancement was evaluated using a semi
      quantitative method and a quantitative method that included measurement of peak
      enhancement (PE), enhancement curve rise time (RT) and wash-in-rate (WiR).
      RESULTS: Ileal wall thickening was observed in all patients. Semi-quantitative
      method was used to observe CD activity in CEUS in 10 cases that perfectly matched
      LDCTE findings. There was a moderate positive correlation between PE and CDAI
      (r=0.65, p<0.001). There was no significant relationship between perfusion
      parameters and laboratory markers of inflammation. CONCLUSIONS: CEUS is a
      promising modality for non-invasive assessment of pathologic ileal
      vascularization in the course of Crohn's disease. Intensity of enhancement in
      CEUS reflects activity of the disease detected in LDCTE and correlates with CDAI.

PMID- 24723986
TI  - Nanotheranostics - application and further development of nanomedicine strategies
      for advanced theranostics.
AB  - Nanotheranostics is to apply and further develop nanomedicine strategies for
      advanced theranostics. This review summarizes the various nanocarriers developed
      so far in the literature for nanotheranostics, which include polymer
      conjugations, dendrimers, micelles, liposomes, metal and inorganic nanoparticles,
      carbon nanotubes, and nanoparticles of biodegradable polymers for sustained,
      controlled and targeted co-delivery of diagnostic and therapeutic agents for
      better theranostic effects with fewer side effects. The theranostic nanomedicine
      can achieve systemic circulation, evade host defenses and deliver the drug and
      diagnostic agents at the targeted site to diagnose and treat the disease at
      cellular and molecular level. The therapeutic and diagnostic agents are
      formulated in nanomedicine as a single theranostic platform, which can then be
      further conjugated to biological ligand for targeting. Nanotheranostics can also
      promote stimuli-responsive release, synergetic and combinatory therapy, siRNA co
      delivery, multimodality therapies, oral delivery, delivery across the blood-brain
      barrier as well as escape from intracellular autophagy. The fruition of
      nanotheranostics will be able to provide personalized therapy with bright
      prognosis, which makes even the fatal diseases curable or at least treatable at
      the earliest stage. 

PMID- 24723989
TI  - Rasch Analysis of US Household Food Security Survey Module in Latino Migrant
      Farmworkers.
AB  - This secondary analysis evaluated the validation of the short version of the US
      Department of Agriculture's Household Food Security Survey Module (HFSSM) in a
      Latino migrant population. The Rasch model assessed the HFSSM's structure, item
      severity levels, and fitness of the sample population. Differential item
      functioning (DIF) analysis explored the invariance of HFSSM response patterns
      between less/more acculturated households. Item infit scores were within an
      adequate range (0.7-1.3). Item severity scores and unidimensionality structure
      supported the HFSSM's theoretical framework. Analysis showed statistically
      nonsignificant DIF contrast between acculturation levels. The adapted HFSSM
      performed in agreement with the theoretical framework of food insecurity as a
      managed process in this Latino migrant population.

PMID- 24723990
TI  - Pediatric Obesity Treatment in Children With Neurodevelopmental Disabilities: A
      Case Series and Review of the Literature.
AB  - Obesity can affect any child, but it occurs disproportionately in children with
      developmental disabilities. Treatment efforts, however, have focused primarily on
      nondisabled children, and more research is needed to determine how current
      approaches can be modified for youth with neurodevelopmental disabilities. This
      article briefly reviews what is currently known about obesity treatment in these
      children and presents a case series describing methods employed by a family
      based, multidisciplinary weight management program in the treatment of obesity.
      Lessons learned from clinical experience are also discussed, with implications
      for collaborating with families of children with disabilities in treatment,
      establishing healthy routines and schedules, setting the pace of treatment
      progression, and minimizing disruptions in the behavior change process. Though
      there are no expert recommendations specifically tailored to obesity treatment in
      children with neurodevelopmental disabilities, existing clinical programs such as
      the one described here can be adapted to better meet the needs of this
      underserved population. Further research is warranted to determine the most
      effective methods for addressing obesity in these children, as has been specified
      as a national health priority.

PMID- 24723991
TI  - Children's Perceptions of Obesity and Health: A Focus Group Study With Hispanic
      Boys.
AB  - OBJECTIVE: Hispanic boys are one of the most at-risk groups for the development
      of obesity, yet few effective interventions have been reported. The objective of
      this study was to assess Hispanic boys' perceptions of health and obesity to
      inform future, targeted interventions. METHODS: This is a qualitative and
      quantitative study of Hispanic boys aged 8 to 12 years in Forsyth County, North
      Carolina (n = 25). Three focus groups were conducted combined with
      anthropometrics and measures of body image. Interview guides were developed to
      elicit children's perceptions of obesity, nutrition, physical activity, and
      family influences over health behaviors. Focus group comments were recorded and
      transcribed. Transcripts were coded using a multistage inductive approach, and
      grounded theory was used to analyze responses. RESULTS: The following 6 themes
      emerged: boys had a limited and superficial understanding of health, nutrition,
      and activity; perceptions of health were based on muscular appearance, frequency
      of exercise, and media messages; boys had negative perceptions of overweight
      children and physical performance; family meals were infrequent and unstructured;
      boys prefer restaurants with fast food, buffets, and entertainment; and
      neighborhood safety influences activity participation. Boys did not mention
      parents as influencers of health and habits. CONCLUSIONS: From their findings,
      the authors have outlined several key areas that will inform clinicians and
      researchers in the prevention and treatment of obesity in this highly vulnerable
      population.

PMID- 24723992
TI  - Pain as a Comorbidity of Pediatric Obesity.
AB  - The purpose of this study was to document the prevalence and characteristics of
      physical pain in a sample of severely obese children and adolescents. In this
      retrospective chart review, primary measures included current and past pain, pain
      intensity, and pain characteristics during a 5-minute walk test. Pain assessments
      for 74 patients (mean age 11.7 years; 53% female; 41% African American) were
      conducted by a physical therapist. Past pain was reported by 73% of the sample,
      with 47% reporting pain on the day of program enrollment. Although average pain
      intensity was moderate (M = 5.5/10), alarmingly, 42% of those with current pain
      reported severe pain (6/10 to 10/10). Overall, pain occurred primarily in the
      lower extremities and with physical activity. Patients reporting current pain had
      a significantly higher body mass index than those reporting no pain. These
      findings suggest that pain is common in severely obese youth, and furthermore,
      that pain should be recognized as a comorbidity of pediatric obesity. Routinely
      screening severely obese children and adolescents for pain presence and intensity
      is recommended.

PMID- 24723993
TI  - Oxidative stress and inflammation in obesity, diabetes, hypertension, and related
      cardiometabolic complications.

PMID- 24723995
TI  - Mitochondria in health and disease.

PMID- 24723994
TI  - Thioredoxin system regulation in the central nervous system: experimental models
      and clinical evidence.
AB  - The reactive oxygen species produced continuously during oxidative metabolism are
      generated at very high rates in the brain. Therefore, defending against oxidative
      stress is an essential task within the brain. An important cellular system
      against oxidative stress is the thioredoxin system (TS). TS is composed of
      thioredoxin, thioredoxin reductase, and NADPH. This review focuses on the
      evidence gathered in recent investigations into the central nervous system,
      specifically the different brain regions in which the TS is expressed.
      Furthermore, we address the conditions that modulate the thioredoxin system in
      both, animal models and the postmortem brains of human patients associated with
      the most common neurodegenerative disorders, in which the thioredoxin system
      could play an important part. 

PMID- 24723996
TI  - Increased oxidative stress response in granulocytes from older patients with a
      hip fracture may account for slow regeneration.
AB  - Proximal femur fracture, a typical fracture of the elderly, is often associated
      with morbidity, reduced quality of life, impaired physical function and increased
      mortality. There exists evidence that responses of the hematopoietic
      microenvironment to fractures change with age. Therefore, we investigated
      oxidative stress markers and oxidative stress-related MAPK activation in
      granulocytes from the young and the elderly with and without fractured long
      bones. Lipid peroxidation levels were increased in the elderly controls and
      patients. Aged granulocytes were more sensitive towards oxidative stress induced
      damage than young granulocytes. This might be due to the basally increased
      expression of SOD-1 in the elderly, which was not further induced by fractures,
      as observed in young patients. This might be caused by an altered MAPK
      activation. In aged granulocytes basal p38 and JNK activities were increased and
      basal ERK1/2 activity was decreased. Following fracture, JNK activity decreased,
      while ERK1/2 and p38 activities increased in both age groups. Control experiments
      with HL60 cells revealed that the observed p38 activation depends strongly on
      age. Summarizing, we observed age-dependent changes in the oxidative stress
      response system of granulocytes after fractures, for example, altered MAPK
      activation and SOD-1 expression. This makes aged granulocytes vulnerable to the
      stress stimuli of the fracture and following surgery. 

PMID- 24723999
TI  - Case reports in the korean journal of family medicine.

PMID- 24723998
TI  - Ultrafast Structural Dynamics of BlsA, a Photoreceptor from the Pathogenic
      Bacterium Acinetobacter baumannii.
AB  - Acinetobacter baumannii is an important human pathogen that can form biofilms and
      persist under harsh environmental conditions. Biofilm formation and virulence are
      modulated by blue light, which is thought to be regulated by a BLUF protein,
      BlsA. To understand the molecular mechanism of light sensing, we have used steady
      state and ultrafast vibrational spectroscopy to compare the photoactivation
      mechanism of BlsA to the BLUF photosensor AppA from Rhodobacter sphaeroides.
      Although similar photocycles are observed, vibrational data together with
      homology modeling identify significant differences in the beta5 strand in BlsA
      caused by photoactivation, which are proposed to be directly linked to downstream
      signaling.

PMID- 24723997
TI  - Toona sinensis inhibits LPS-induced inflammation and migration in vascular smooth
      muscle cells via suppression of reactive oxygen species and NF-kappaB signaling
      pathway.
AB  - Toona sinensis is one of the most popular vegetarian cuisines in Taiwan and it
      has been shown to possess antioxidant, antiangiogenic, and anticancer properties.
      In this study, we investigated the antiatherosclerotic potential of aqueous leaf
      extracts from Toona sinensis (TS; 25-100 MUg/mL) and its major bioactive
      compound, gallic acid (GA; 5 MUg/mL), in LPS-treated rat aortic smooth muscle
      (A7r5) cells. We found that pretreatment with noncytotoxic concentrations of TS
      and GA significantly inhibited inflammatory NO and PGE2 production by
      downregulating their precursors, iNOS and COX-2, respectively, in LPS-treated
      A7r5 cells. Furthermore, TS and GA inhibited LPS-induced intracellular ROS and
      their corresponding mediator, p47(phox). Notably, TS and GA pretreatment
      significantly inhibited LPS-induced migration in transwell assays. Gelatin
      zymography and western blotting demonstrated that treatment with TS and GA
      suppressed the activity or expression of MMP-9, MMP-2, and t-PA. Additionally, TS
      and GA significantly inhibited LPS-induced VEGF, PDGF, and VCAM-1 expression.
      Further investigation revealed that the inhibition of iNOS/COX-2, MMPs, growth
      factors, and adhesion molecules was associated with the suppression of NF-kappaB
      activation and MAPK (ERK1/2, JNK1/2, and p38) phosphorylation. Thus, Toona
      sinensis may be useful for the prevention of atherosclerosis.

PMID- 24724000
TI  - Impact of clinical performance examination on incoming interns' clinical
      competency in differential diagnosis of headache.
AB  - BACKGROUND: In Korea, clinical performance examination (CPX) has been included in
      license examination for medical doctors since 2009 in order to improve clinical
      performance of medical students. This study aimed to evaluate the contribution of
      CPX to medical education. METHODS: Clinical competency in the differential
      diagnosis of secondary headache was compared between the incoming interns in 2009
      unexposed to CPX and the incoming interns in 2010 exposed to CPX, using the data
      of patients who visited the emergency department due to headache (181 patients
      seen by 60 CPX non-exposed interns and 150 patients seen by 50 CPX-exposed
      interns). We obtained the data by reviewing electronic medical records and
      nominal lists of doctors. Clinical competency was assessed by sensitivity and
      specificity between the diagnostic impression by interns and the final diagnosis.
      The association between CPX exposure and clinical competency in secondary
      headache diagnosis was evaluated using multiple logistic regression analysis.
      RESULTS: When we assessed clinical competency on the basis of all listed
      diagnostic impressions, sensitivity and specificity were 67.9% and 80.0%,
      respectively, for headaches seen by CPX-exposed interns, and 51.7%, and 71.7%,
      respectively, for headaches seen by CPX non-exposed interns. Multivariable
      adjusted logistic regression analysis showed exposure to CPX was not associated
      with increased competency for identifying secondary headache. CONCLUSION:
      Exposure to CPX as a part of the medical license examination was not effective
      for the improvement of clinical competency of interns in identifying secondary
      headache.

PMID- 24724001
TI  - Association of Leisure Time Physical Activity and Metabolic Syndrome over 40
      Years.
AB  - BACKGROUND: This study aimed to investigate the relationship between leisure time
      physical activities (LTPA) and metabolic syndrome (MS). METHODS: Five thousand
      seven hundred and thirty two adults 40 years old or older were enrolled in the
      study from April 2009 to December 2010. National Cholesterol Education Program's
      Adult Treatment Panel III was used for the criteria of MS, and Minnesota Leisure
      Time Physical Activity Questionnaire was used to measure LTPA. After adjusted
      covariates (age, hypertension, smoking, drinking, education level, household
      income level, work time physical activities, and menopause for females), the
      relationship between LTPA and MS was analyzed using logistic regression analysis.
      RESULTS: The prevalence of MS was 22.8% in men, and 14.1% in women. Average LTPA
      was 1,498 kcal/wk in men, and 1,308 kcal/wk in women. After adjustment for
      covariates, the odds ratios of middle and low LTPA compared with high LTPA were
      1.06 (0.87-1.34), 1.54 (1.08-1.75), for women, this same association was not seen
      in men. The prevalence of MS was 22.8% in men and 14.1% in women, and their LTPA
      burned 1,498 and 1,308 kcal/wk, respectively. When the odds ratio of MS for the
      high LTPA group was set at 1.0, the odds ratio of MS was 1.06 (0.87-1.34) in the
      middle LTPA group and 1.54 (1.08-1.75) in the low LTPA group in women, which
      showed that the MS risk increased when the LTPA was lower. This same association
      was not seen in men. CONCLUSION: LTPA was independently associated with metabolic
      syndrome, but only for women.

PMID- 24724002
TI  - Higher Serum Heavy Metal May Be Related with Higher Serum gamma
      Glutamyltransferase Concentration in Koreans: Analysis of the Fifth Korea
      National Health and Nutrition Examination Survey (KNHANES V-1, 2, 2010, 2011).
AB  - BACKGROUND: Abnormal serum gamma-glutamyltransferase (gamma-GT) may be an early
      and sensitive marker for oxidative stress. This study was performed to evaluate
      the association between serum heavy metals and gamma-GT concentration. METHODS:
      This study is a cross-sectional analysis based on data from Korean National
      Health and Nutrition Examination Survey (V-1, 2, 2010, 2011) regarding serum
      heavy metal concentrations (lead, mercury, and cadmium) as well as serum gamma
      GT. Serum heavy metals were categorized into tertiles, and serum gamma-GT
      concentration was compared using an analysis of covariance test after relevant
      variable adjustments. In addition, we evaluated the odds ratio (OR) of having the
      highest tertile of serum gamma-GT in each heavy metal tertile using logistic
      regression. RESULTS: The mean serum lead, mercury, and cadmium concentrations
      were 2.67, 5.08, and 1.02 ug/dL in men and 1.95, 3.60, and 1.21 ug/dL in women,
      respectively. Partial correlation showed a significant positive relation between
      each heavy metal and serum gamma-GT concentration. Comparing serum gamma-GT
      concentration by the tertile of each heavy metal, serum gamma-GT concentration
      showed a significant increase as the tertiles of serum mercury and cadmium in men
      and that of serum mercury in women increased, but not with lead. The OR of having
      the highest tertile of serum gamma-GT was significant for cadmium in men (OR,
      4.02; 95% confidence interval [CI], 2.54 to 6.35) and mercury in women (OR, 2.00;
      95% CI, 1.29 to 3.10) in the top tertile of each heavy metal. CONCLUSION: Higher
      serum heavy metal concentration may be related with higher serum gamma-GT
      concentration. In particular, serum cadmium in men and mercury in women showed
      significant correlation with serum gamma-GT concentration.

PMID- 24724003
TI  - Association between Hepatitis B Surface Antigen Seropositivity and Metabolic
      Syndrome.
AB  - BACKGROUND: Infection with hepatitis B virus (HBV) may be a risk factor for
      cardiovascular disease. We investigated the relationship between HBV infection
      and metabolic syndrome. METHODS: We performed a cross-sectional study of 9,474
      Korean men and women who were at least 20 years old and who underwent a routine
      health check-up at Ulsan University Hospital in Ulsan, South Korea between March
      2008 and February 2009. The associations of hepatitis B surface antigen (HBsAg)
      seropositivity with the presence of metabolic syndrome and its components were
      investigated by logistic regression analysis. Data were analyzed separately for
      males and females. RESULTS: HBsAg seropositivity was significantly negatively
      associated with hypertriglyceridemia and metabolic syndrome in men (odds ratio
      [OR], 0.39; 95% confidence interval [CI], 0.29 to 0.50; P < 0.001 and OR, 0.75;
      95% CI, 0.57 to 0.98, P = 0.033). In women, HBsAg seropositivity was also
      significantly negatively associated with hypertriglyceridemia, but not with
      metabolic syndrome (OR, 0.40; 95% CI, 0.17 to 0.91; P = 0.029 and OR, 0.80; 95%
      CI, 0.38 to 1.66, P = 0.545). CONCLUSION: HBV infection was significantly
      negatively associated with hypertriglyceridemia and metabolic syndrome in men and
      hypertriglyceridemia in women.

PMID- 24724004
TI  - Association between Bone Mineral Density and Sleep Duration in the Korean Elderly
      Population.
AB  - BACKGROUND: An association between sleep duration and a wide spectrum of diseases
      has been reported, but little is known about its relationship with bone mineral
      density (BMD). Previously conducted studies in Korea and abroad have reported
      results that are controversial. The present study sought to assess whether sleep
      duration can be considered an independent risk factor of osteoporosis. METHODS:
      We included participants over the age of 60 years with data on self-reported
      habitual sleep duration and BMD measured with dual X-ray absorptiometry.
      Comprehensive data on the study sample was obtained from the Korea National
      Health and Nutritional Survey performed from 2008 to 2010. Sex-stratified
      multiple regression analyses were conducted with adjustments for possible
      confounding factors. RESULTS: There was a significant inverse dose-dependent
      association between sleep duration and BMD measured at total hip, femur neck, and
      lumbar spine for women and total hip and femur neck for men. Sex-stratified
      regression analyses adjusted for age and body mass index revealed that sleep
      duration had a negative correlation with BMD at total hip and femoral neck for
      both women (beta = -0.0048; P = 0.0172 for total hip, beta = -0.0037; P = 0.0303
      for femur neck) and men (beta = -0.0057; P = 0.0218 for total hip, beta = 
      0.0057; P = 0.0143 for femur neck). For women, the significance remained after
      further adjustment of confounding variables. CONCLUSION: Prolonged sleep duration
      appears to have a significant association with lower total hip and femur neck BMD
      in elderly women but not in elderly men.

PMID- 24724005
TI  - The Relationship between Serum 25-Hydroxyvitamin D, Parathyroid Hormone and the
      Glomerular Filtration Rate in Korean Adults: The Korea National Health and
      Nutrition Examination Survey between 2009 and 2011.
AB  - BACKGROUND: The glomerular filtration rate (GFR) decreases with age, while
      parathyroid hormone (PTH) increases. There are a few reports only on the
      relationship between GFR and PTH under the category of serum 25-hydroxyvitamin D
      (25[OH]D) concentration. METHODS: Using the Korea National Health and Nutrition
      Examination Survey (KNHANES) data, a cross-sectional study was conducted on the
      association between serum 25(OH)D concentration, GFR and PTH in Korean adults
      aged 50 years or older. Serum PTH concentration was compared to the tertiles of
      GFR after adjustment for relevant variables. In addition, the serum PTH
      concentration was compared with the GFR under the category of serum 25(OH) D
      concentration (<20, 20-30, >30 ng/mL). RESULTS: The mean estimated GFR (eGFR) was
      74.8 mL/min in men and 73.1 mL/min in women. The mean PTH and 25(OH) D was 66.8
      pg/mL, 20.5 ng/mL in men and 69.0 pg/mL, 18.2 ng/mL in women. The serum PTH
      concentration showed a significant negative correlation with the serum 25(OH) D
      and eGFR in both genders. The serum PTH concentration significantly increased at
      the lower tertile of eGFR in male adults In addition, a decrease of serum PTH
      concentration was marked in the vitamin D sufficient male adults (>30 ng/mL).
      CONCLUSION: This present study demonstrated that serum PTH concentration showed
      negative correlation with eGFR, however, serum PTH increase may be minimized by
      maintaining proper serum 25(OH)D concentrations under similar eGFR status in
      Korean adults aged 50 and above.

PMID- 24724006
TI  - Comments on statistical issues in march 2014.

PMID- 24724007
TI  - UK wide survey on the prevention of post-ERCP pancreatitis.
AB  - OBJECTIVE: In 2010, the European Society of Gastrointestinal Endoscopy delivered
      guidelines on the prophylaxis of postendoscopic retrograde
      cholangiopancreatography (post-ERCP) pancreatitis (PEP). These included Grade A
      recommendations advising the use of prophylactic pancreatic stent (PPS) and non
      steroidal anti-inflammatory drugs (NSAIDs) in high-risk cases. Our study aim was
      to capture the current practice of UK biliary endoscopists in the prevention of
      PEP. DESIGN: In summer 2012, an anonymous online 15-item survey was emailed to
      373 UK consultant gastroenterologists, gastrointestinal surgeons and radiologists
      identified to perform ERCP. RESULTS: The response rate was 59.5% (222/373). Of
      the respondents, 52.5% considered ever using PPS for the prevention of PEP. PPS
      users always attempted insertion for the following procedural risk factors:
      pancreatic sphincterotomy (48.9%), suspected sphincter of Oddi dysfunction
      (46.5%), pancreatic duct instrumentation (35.9%), previous PEP (25.2%), precut
      sphincterotomy (8.5%) and pancreatic duct injection (7.8%). Prophylactic NSAID
      use was significantly associated with attempts at PPS placement (p<0.001). 64.1%
      of non-PPS users cited a lack of conviction in their benefit as the main reason
      for their decision. Self-reported pharmacological use rates for PEP prevention
      were: NSAIDs (34.6%), antibiotics (20.6%), rapid intravenous fluids (13.2%) and
      octreotide (1.6%). 6% routinely measured amylase post-ERCP. CONCLUSIONS: Despite
      strong evidence-based guidelines for prevention of PEP, less than 53% of ERCP
      practitioners use pancreatic stenting or NSAIDs. This suggests a need for the
      development of British Society of Gastroenterology guidelines to increase
      awareness in the UK. Even among stent users, PPS are being underused for most
      high-risk cases. Prophylactic pharmacological measures were rarely used as was
      routine post-ERCP serum amylase measurement.

PMID- 24715972
TI  - A letter to the Master Clinician.
AB  - In this commentary, the author writes a letter to the Master Clinician about his
      concerns regarding the teaching responsibilities of current faculty members
      during ward rounds. This short essay highlights the transition that has been
      noticed in medical training in the last decade. 

PMID- 24715973
TI  - Two fatal cases of melioidosis on the Thai-Myanmar border.
AB  - Melioidosis is endemic in areas of Southeast Asia, however, there are no
      published reports from the Thai-Myanmar border. We report the first two
      documented cases of fatal melioidosis in this region. This is of great public
      health importance and highlights the need to both increase clinical awareness of
      melioidosis on the Thai-Myanmar border, and to assess the true burden of disease
      in the area through improved case detection and Burkholderia pseudomallei
      prevalence studies. 

PMID- 24715974
TI  - Pericardial synovial sarcoma: challenges in diagnosis and management.
AB  - INTRODUCTION: Pericardial synovial sarcoma is an extremely rare tumor with poor
      prognosis. Timely diagnosis and aggressive multimodal management improves patient
      outcome. We present our experience of diagnosis and management of a young patient
      with monophasic synovial sarcoma arising from pericardium. CASE: A 27-year-old
      man presented with dyspnea and cough of three weeks duration. Examination
      revealed sinus tachycardia, distant heart sounds and elevated jugular venous
      pressure. Chest X-ray showed widened mediastinum. Transthoracic echocardiogram
      (TTE) noted large pericardial effusion with tamponade physiology. Therapeutic
      pericardiocentesis yielded hemorrhagic fluid. Computed tomography (CT) of the
      chest showed persistent pericardial effusion and a left anterior mediastinal
      mass. Left anterior thoracotomy, pericardial window and left anterior
      mediastinotomy were done, revealing a well-encapsulated gelatinous tumor
      originating from the pericardium. Histology and immunohistochemical profile
      showed the tumor to be a monophasic synovial sarcoma. Fluorescent in-situ
      hybridization (FISH) was positive for SS18 (SYT) gene rearrangement on chromosome
      18q11, substantiating the diagnosis. Work-up for metastases was negative. Neo
      adjuvant chemotherapy with high dose ifosfamide led to substantial reduction in
      the size of the tumor. The patient underwent surgical resection and external beam
      radiation therapy (EBRT) post surgery. He had symptom-free survival for 8 months
      prior to local recurrence. This was managed with left lung upper lobectomy and
      follow-up chemotherapy with docetaxel. The patient is currently stable with an
      acceptable functional status. CONCLUSION: In patients with pericardial effusions
      of unknown etiology, multiple modalities of cardiac imaging must be employed if
      there is suspicion of a pericardial mass. CT and magnetic resonance imaging (MRI)
      are useful to evaluate for pericardial thickening or masses in addition to TTE.
      Treatment of synovial sarcoma is not well established. Surgery is the cornerstone
      of treatment. In non-resectable tumors, aggressive neo-adjuvant chemotherapy with
      ifosfamide followed by surgical resection and EBRT may lead to improved outcome.

PMID- 24715979
TI  - Drugs acting on central nervous system (CNS) targets as leads for non-CNS
      targets.
AB  - Innovative drug discovery approaches are currently needed to rejuvenate the
      shrinking product pipelines of the pharmaceutical companies across the globe.
      Here a theme is presented - the use of central nervous system (CNS) drugs as
      leads for non-CNS targets. The approach is related to the use of existing drugs
      for new indications. Suitable chemical modifications of the CNS drugs abolish
      their CNS penetration. These novel analogs may then be screened for activity
      against non-CNS targets. Careful selection of the appropriate structural
      modifications remains the key to success. 

PMID- 24724012
TI  - Phospholipid micelle encapsulated gadolinium oxide nanoparticles for imaging and
      gene delivery.
AB  - We encapsulated gadolinium oxide (Gd2O3) nanoparticles within phospholipid
      micelles as a novel low cytotoxic T1-weighted MRI imaging contrast agent (MGdNPs)
      that can also deliver small molecules such as DNA plasmids. MGdNPs show
      relatively good MRI relaxivity values, negligible cytotoxicity, excellent
      cellular uptake and expression of DNA plasmids in vivo. Biodistribution studies
      in mice show that intranasal and intraperitoneal administration of MGdNPs can
      effectively target specific organs.

PMID- 24724013
TI  - Novel Association of Rectal Evacuation Disorder and Rumination Syndrome:
      Diagnosis, Co-morbidities and Treatment.
AB  - BACKGROUND: Patients with disorders of gastrointestinal function may undergo
      unnecessary treatment if misdiagnosed as motility disorders. OBJECTIVE: To report
      on clinical features, medical, surgical and psychiatric co-morbidities, and prior
      treatments of a patient cohort diagnosed concurrently with non-psychogenic
      rumination syndrome and pelvic floor dysfunction (also termed rectal evacuation
      disorder). METHODS: From a consecutive series (1994-2013) of 438 outpatients with
      rectal evacuation disorders in the practice of a single gastroenterologist at a
      tertiary care center, 57 adolescents or adults were diagnosed with concomitant
      rumination syndrome. All underwent formal psychological assessment or completed
      validated questionnaires. RESULTS: All 57 patients (95% female) fulfilled Rome
      III criteria for rumination syndrome; rectal evacuation disorder was confirmed by
      testing of anal sphincter pressures and rectal balloon evacuation. Prior to
      diagnosis, most patients underwent multiple medical and surgical treatments
      (gastrostomy, gastric fundoplication, other gastric surgery, ileostomy,
      colectomy) for their symptoms. Psychological co-morbidity was identified in 93%
      of patients. Patients were managed predominantly with psychological and
      behavioral approaches: diaphragmatic breathing for rumination and biofeedback
      retraining for pelvic floor dysfunction. CONCLUSIONS: Awareness of concomitant
      rectal evacuation disorder and rumination syndrome and prompt identification of
      psychological co-morbidity are keys to instituting behavioral and psychological
      methods to avoid unnecessary treatment.

PMID- 24724014
TI  - Medium-term visual outcomes of apodized diffractive multifocal intraocular lens
      with +3.00 d addition power.
AB  - Purpose. To evaluate 2-year visual acuities and questionnaire after bilateral
      implantation of SN6AD1 multifocal intraocular lens (MIOL) or SN60WF IOL. Methods.
      Patients randomly scheduled for bilateral implantation of SN6AD1 MIOL and SN60WF
      IOL with 2-year follow-up were enrolled. Uncorrected/corrected distance and near
      visual acuity, uncorrected intermediate visual acuity at 63 cm under high and low
      contrast, reading activity, the defocus curve, and a quality-of-life
      questionnaire were evaluated. Results. Each group comprised 20 patients.
      Uncorrected intermediate visual acuities and uncorrected near visual acuity were
      better in SN6AD1 group than in SN60WF group (P = 0.005, P = 0.011, and P <
      0.001). In SN6AD1 group, the uncorrected intermediate and near visual acuities 1
      year and 2 years postoperatively were reduced than postoperative 3-month
      outcomes, respectively. SN6AD1 group reported superior overall spectacle
      independence and inferior satisfaction. SN6AD1 group had a longer reading
      newspaper duration than SN60WF group (P = 0.036). When using mobile phone, SN6AD1
      group had a more comfortable distance than SN60WF group (P < 0.001) and higher
      speed of reading fixed text message (P < 0.001). Conclusion. SN6AD1 MIOL provided
      a satisfactory full range of visual acuities and questionnaire performance 2
      years postoperatively. One-year and 2-year uncorrected near and intermediate
      visual acuities of SN6AD1 MIOL were lower than those 3 months postoperatively. 

PMID- 24724015
TI  - Comparison of the Retinal Straylight in Pseudophakic Eyes with PMMA, Hydrophobic
      Acrylic, and Hydrophilic Acrylic Spherical Intraocular Lens.
AB  - Purpose. To investigate the intraocular straylight value after cataract surgery.
      Methods. In this study, 76 eyes from 62 patients were subdivided into three
      groups. A hydrophobic acrylic, a hydrophilic acrylic, and a PMMA IOL were
      respectively, implanted in 24 eyes, 28 eyes, and 24 eyes. Straylight was measured
      using C-Quant at 1 week and 1 month postoperatively in natural and dilated
      pupils. Results. The hydrophilic acrylic IOLs showed significantly lower
      straylight values than those of the hydrophobic acrylic IOLs in dilated pupils at
      1 week and 1 month after surgery (P < 0.05). However, the straylight values of
      the hydrophilic acrylic IOLs were the lowest among the three IOL groups. No
      significant difference was observed in straylight between 1 week and 1 month
      postoperatively in each group with natural and dilated pupils (P > 0.05).
      Moreover, no significant difference was found in straylight between natural and
      dilated pupils in each group at 1 week and 1 month postoperatively (P > 0.05).
      Conclusions. Although the hydrophobic acrylic IOL induced more intraocular
      straylight, straylight differences among the 3 IOLs were minimal. Pupil size
      showed no effect on intraocular straylight; the intraocular straylight was stable
      1 week after surgery. 

PMID- 24724016
TI  - The Effect of ND:YAG Laser Posterior Capsulotomy Size on Refraction, Intraocular
      Pressure, and Macular Thickness.
AB  - Purpose. The aim of this study is to examine the influence of capsulotomy size
      on, spherical equivalent (SE), intraocular pressure (IOP), and macular thickness.
      Materials and Methods. Sixty-eight patients were examined preoperatively and 1,
      4, and 12 weeks after Nd:YAG capsulotomy. Patients were divided into two groups
      based on the postoperative capsulotomy size. Changes in SE, IOP, and macular
      thickness were compared between two groups. Results. We found a higher hyperopic
      shift in large capsulotomy group. In both groups 1 and 2, IOP increased 1 week
      postoperatively. Intraocular pressure rise in group 2 was higher than in group 1.
      Both groups had increased macular thickness at 1 week postoperatively. The degree
      of macular thickening was similar in group 1 and group 2. Comment. Patients who
      underwent a larger capsulotomy have a higher hyperopic shift and IOP elevation.
      Rise in macular thickness was similar in large and small capsulotomy groups. 

PMID- 24724017
TI  - Aspergillus 6V4, a Strain Isolated from Manipueira, Produces High Amylases Levels
      by Using Wheat Bran as a Substrate.
AB  - The aim of this study was screening fungi strains, isolated from manipueira (a
      liquid subproduct obtained from the flour production of Manihot esculenta), for
      amylases production and investigating production of these enzymes by the strain
      Aspergillus 6V4. The fungi isolated from manipueira belonged to Ascomycota
      phylum. The strain Aspergillus 6V4 was the best amylase producer in the screening
      assay of starch hydrolysis in petri dishes (ASHPD) and in the assay in submerged
      fermentation (ASbF). The strain Aspergillus 6V4 produced high amylase levels (335
      UI/L) using wheat bran infusion as the exclusive substrate and the
      supplementation of this substrate with peptone decreased the production of this
      enzyme. The moisture content of 70% was the best condition for the production of
      Aspergillus 6V4 amylases (385 IU/g) in solid state fermentation (SSF). 

PMID- 24724018
TI  - Exploring T cell reactivity to gliadin in young children with newly diagnosed
      celiac disease.
AB  - Class II major histocompatibility molecules confer disease risk in Celiac disease
      (CD) by presenting gliadin peptides to CD4 T cells in the small intestine.
      Deamidation of gliadin peptides by tissue transglutaminase creates immunogenic
      peptides presented by HLA-DQ2 and DQ8 molecules to activate proinflammatory CD4 T
      cells. Detecting gliadin specific T cell responses from the peripheral blood has
      been challenging due to low circulating frequencies and heterogeneity in response
      to gliadin epitopes. We investigated the peripheral T cell responses to alpha and
      gamma gliadin epitopes in young children with newly diagnosed and untreated CD.
      Using peptide/MHC recombinant protein constructs, we are able to robustly
      stimulate CD4 T cell clones previously derived from intestinal biopsies of CD
      patients. These recombinant proteins and a panel of alpha- and gamma-gliadin
      peptides were used to assess T cell responses from the peripheral blood.
      Proliferation assays using peripheral blood mononuclear cells revealed more CD4 T
      cell responses to alpha-gliadin than gamma-gliadin peptides with a single
      deamidated alpha-gliadin peptide able to identify 60% of CD children. We conclude
      that it is possible to detect T cell responses without a gluten challenge or in
      vitro stimulus other than antigen, when measuring proliferative responses. 

PMID- 24724019
TI  - Exploring personality features in patients with affective disorders and history
      of suicide attempts: a comparative study with their parents and control subjects.
AB  - Personality traits are important candidate predictors of suicidal behavior.
      Several studies have reported an association between personality/temperament
      traits and suicidal behavior, suggesting personality traits as intermediary
      phenotypes related to suicidal behavior. Thus, it is possible that suicide
      attempts can be accounted for by increased familial rates of risk personality
      traits. The aim of this work was to evaluate personality traits in affective
      disorder patients with attempted suicide and to compare them with the personality
      trait scores of their parents. In addition, ITC scores in the two groups were
      compared with a healthy control sample. The patients evaluated met the DSM-IV
      criteria for major depression disorder or dysthymia and had a documented history
      of suicide attempts. Psychiatric diagnoses of patients and parents were done
      according to the SCID-I and the personality was assessed using the Temperament
      and Character Inventory. We analyzed 49 suicide attempt subjects and their
      parents (n = 95) and 89 control subjects. We observed that temperament and
      character dimensions were similar between patients and their parents (P > 0.05).
      In particular, we observed that high HA and low P, SD, and CO were shared among
      families. Our study is the first to report that the personality traits of
      affective disorder patients with a history of attempted suicide are shared
      between patients and their parents. 

PMID- 24724020
TI  - Interprofessional collaboration in the mental health services in norway.
AB  - The aim of this study was to describe and interpret interprofessional
      collaboration between healthcare professionals (HCPs) working at the district
      psychiatric centre (DPC) and employed in community mental health care (CMHC)
      using a dialogue-oriented co-operative approach. Data were collected by means of
      multistage focus groups and qualitative content analysis was performed. The main
      theme "development of interprofessional collaboration by means of organisational
      strategies and interactional styles" encompassed the following categories:
      "improved communication skills," "developing structures for coordination and
      responsibility" and " increased professional insight into the values and
      conditions necessary for decision-making." In conclusion, more attention should
      be paid to leadership in terms of coordination and feedback. The HCPs must be
      acknowledged, understood and strengthened in their work to improve the quality of
      CMHC. Finally, we recommend that a range of organisational and administrative
      models of care be used in order to support improvement work. 

PMID- 24724021
TI  - Long-Term Persistency of Abnormal Heart Rate Variability following Long NICU Stay
      and Surgery at Birth.
AB  - Preterm birth is associated with painful procedures during the neonatal intensive
      care unit (NICU) stay. Full-term newborns can also experience pain, following
      surgery. These procedures can have long-lasting consequences. It has been shown
      that children born preterm show pain responses and cardiac alterations. This
      study aimed to explore the heart rate reactivity to pain in 107 subjects born
      either preterm or full-term who were between 7 and 25 years old at testing. We
      also evaluated the effect of pain experienced at birth, as represented by a
      longer NICU stay, time under ventilation, and surgery at birth. Participants were
      asked to immerse their right forearm in 10 degrees C water for 2 minutes.
      Electrocardiograms were recorded at baseline and during the immersion procedure.
      Full-term subjects showed a stable increase in heart rate throughout the
      procedure, whereas preterm ones showed a strong increase at the beginning, which
      decreased over time. Also, preterm and full-term subjects who experienced pain at
      birth showed higher resting heart rate, stronger sympathetic activity, and lower
      cardiac vagal activity. Our study demonstrated a long-term impact of a long NICU
      stay and surgery at birth on cardiac autonomic activity. This could lead to
      impaired reactions to pain or stress in later life. 

PMID- 24724022
TI  - Longitudinal imaging of cancer cell metastases in two preclinical models: a
      correlation of noninvasive imaging to histopathology.
AB  - Metastatic spread is the leading cause of death from cancer. Early detection of
      cancer at primary and metastatic sites by noninvasive imaging modalities would be
      beneficial for both therapeutic intervention and disease management. Noninvasive
      imaging modalities such as bioluminescence (optical), positron emission
      tomography (PET)/X-ray computed tomography (CT), and magnetic resonance imaging
      (MRI) can provide complementary information and accurately measure tumor growth
      as confirmed by histopathology. Methods. We validated two metastatic tumor
      models, MDA-MD-231-Luc and B16-F10-Luc intravenously injected, and 4T1-Luc cells
      orthotopically implanted into the mammary fat pad. Longitudinal whole body
      bioluminescence imaging (BLI) evaluated metastasis, and tumor burden of the
      melanoma cell line (B16-F10-Luc) was correlated with (PET)/CT and MRI. In
      addition, ex vivo imaging evaluated metastasis in relevant organs and
      histopathological analysis was used to confirm imaging. Results. BLI revealed
      successful colonization of cancer cells in both metastatic tumor models over a 4
      week period. Furthermore, lung metastasis of B16-F10-Luc cells imaged by PET/CT
      at week four showed a strong correlation (R (2) = 0.9) with histopathology. The
      presence and degree of metastasis as determined by imaging correlated (R (2) =
      0.7) well with histopathology findings. Conclusions. We validated two metastatic
      tumor models by longitudinal noninvasive imaging with good histopathology
      correlation. 

PMID- 24724023
TI  - Four-quadrant facial function in dysphagic patients after stroke and in healthy
      controls.
AB  - This study aims to examine any motility disturbance in any quadrant of the face
      other than the quadrant innervated by the lower facial nerve contralateral to the
      cortical lesion after stroke. Thirty-one stroke-afflicted patients with
      subjective dysphagia, consecutively referred to a swallowing centre, were
      investigated with a facial activity test (FAT) in all four facial quadrants and
      with a swallowing capacity test (SCT). Fifteen healthy adult participants served
      as FAT controls. Sixteen patients were judged to have a central facial palsy (FP)
      according to the referring physician, but all 31 patients had a pathological FAT
      in the lower quadrant contralateral to the cortical lesion. Simultaneous
      pathology in all four quadrants was observed in 52% of stroke-afflicted patients
      with dysphagia; some pathology in the left or right upper quadrant was observed
      in 74%. Dysfunction in multiple facial quadrants was independent of the time
      interval between stroke and study inclusion. All patients except two had a
      pathological SCT. All the controls had normal activity in all facial quadrants.
      In summary the majority of poststroke patients with dysphagia have subclinical
      orofacial motor dysfunction in three or four facial quadrants as assessed with a
      FAT. However, whether subclinical orofacial motor dysfunction can be present in
      stroke-afflicted patients without dysphagia is unknown. 

PMID- 24724024
TI  - Dislocability of localization devices for nonpalpable breast lesions:
      experimental results.
AB  - Purpose. For accurate resection of nonpalpable malignant breast lesions with a
      tumor-free resection rim, an exact and stable wire localization is essential. We
      tested the resistance towards traction force of different localization devices
      used in our clinic for breast lesions in two types of tissue. Materials and
      Methods. Eight different commercially available hook-wire devices were examined
      for resistance towards traction force using an analogue spring scale. Results.
      Most systems showed a high level of movement already under small traction force.
      Retractable systems with round hooks such as the Bard DuaLok , the Fil d'Ariane,
      and the RPLN Breast Localization Device withstood less traction force than the
      other systems. However, the Bard DuaLok system was very resistant towards a small
      traction force of 50 g when compared to the other systems. The Ultrawire Breast
      Localization Device withstood the most traction force in softer tissue and Kopans
      Breast Lesion Localization Needle withstood the most force in harder tissue.
      Conclusion. The Ultrawire Breast Localization Device and Kopans Breast Lesion
      Localization Needle withstood the most traction force. In general retractable
      systems withstand less traction force than nonretractable systems. 

PMID- 24724025
TI  - Dimensional information-theoretic measurement of facial emotion expressions in
      schizophrenia.
AB  - Altered facial expressions of emotions are characteristic impairments in
      schizophrenia. Ratings of affect have traditionally been limited to clinical
      rating scales and facial muscle movement analysis, which require extensive
      training and have limitations based on methodology and ecological validity. To
      improve reliable assessment of dynamic facial expression changes, we have
      developed automated measurements of facial emotion expressions based on
      information-theoretic measures of expressivity of ambiguity and distinctiveness
      of facial expressions. These measures were examined in matched groups of persons
      with schizophrenia (n = 28) and healthy controls (n = 26) who underwent video
      acquisition to assess expressivity of basic emotions (happiness, sadness, anger,
      fear, and disgust) in evoked conditions. Persons with schizophrenia scored higher
      on ambiguity, the measure of conditional entropy within the expression of a
      single emotion, and they scored lower on distinctiveness, the measure of mutual
      information across expressions of different emotions. The automated measures
      compared favorably with observer-based ratings. This method can be applied for
      delineating dynamic emotional expressivity in healthy and clinical populations. 

PMID- 24724026
TI  - Not all distraction is bad: working memory vulnerability to implicit
      socioemotional distraction correlates with negative symptoms and functional
      impairment in psychosis.
AB  - This study investigated implicit socioemotional modulation of working memory (WM)
      in the context of symptom severity and functional status in individuals with
      psychosis (N = 21). A delayed match-to-sample task was modified wherein task
      irrelevant facial distracters were presented early and briefly during the
      rehearsal of pseudoword memoranda that varied incrementally in load size (1, 2,
      or 3 syllables). Facial distracters displayed happy, sad, or emotionally neutral
      expressions. Implicit socioemotional modulation of WM was indexed by subtracting
      task accuracy on nonfacial geometrical distraction trials from facial distraction
      trials. Results indicated that the amount of implicit socioemotional modulation
      of high WM load accuracy was significantly associated with negative symptoms (r =
      0.63, P < 0.01), role functioning (r = -0.50, P < 0.05), social functioning (r = 
      0.55, P < 0.01), and global assessment of functioning (r = -0.53, P < 0.05).
      Specifically, greater attentional distraction of high WM load was associated with
      less severe symptoms and functional impairment. This study demonstrates the
      importance of the WM-socioemotional interface in influencing clinical and
      psychosocial functional status in psychosis. 

PMID- 24724027
TI  - Persistent microalbuminuria in human immunodeficiency virus infected children in
      kano, Nigeria.
AB  - Microalbuminuria has been reported to be a precursor of HIV related renal
      disease, which if detected early and coupled with appropriate intervention may
      slow or retard the progress of the disease. One hundred and seventy-eight HIV
      infected children aged 15 years and below were recruited from the Paediatric
      Infectious Disease Clinic of Aminu Kano Teaching Hospital (AKTH), Kano, to
      determine the prevalence of persistent microalbuminuria using the albumin
      creatinine ratio (ACR). Early morning urine samples and spot urine samples were
      analyzed using a dipstick specific for microalbumin. Those who tested positive
      had their samples reanalyzed in the laboratory using immunometric assay and Jaffe
      reaction method for albumin and creatinine, respectively. Patients that had ACR
      of 30-300 mg/g were said to have microalbuminuria and had their urine samples
      retested after 6 to 8 weeks. Twelve children (6.7%) had persistent
      microalbuminuria and had a mean age of 7.5 +/- 3.3 years, with a male to female
      ratio of 1 : 1. There was no significant relationship between the finding of
      microalbuminuria and age, sex, duration of infection, and the use of highly
      active antiretroviral therapy. Periodic screening for microalbuminuria using
      albumin specific dipstick should be considered for children with HIV infection. 

PMID- 24724028
TI  - In-depth profiling of the peripheral blood mononuclear cells proteome for
      clinical blood proteomics.
AB  - Peripheral blood mononuclear cells (PBMCs) are an easy accessible cellular part
      of the blood organ and, along with platelets, represent the only site of active
      gene expression in blood. These cells undergo immunophenotypic changes in various
      diseases and represent a peripheral source of monitoring gene expression and
      posttranslational modifications relevant to many diseases. Little is known about
      the source of many blood proteins and we hypothesise that release from PBMCs
      through active and passive mechanisms may account for a substantial part of the
      plasma proteome. The use of state-of-the-art proteomic profiling methods in PBMCs
      will enable minimally invasive monitoring of disease progression or response to
      treatment and discovery of biomarkers. To achieve this goal, detailed mapping of
      the PBMC proteome using a sensitive, robust, and quantitative methodological
      setup is required. We have applied an indepth gel-free proteomics approach using
      tandem mass tags (TMT), unfractionated and SCX fractionated PBMC samples, and LC
      MS/MS with various modulations. This study represents a benchmark in deciphering
      the PBMC proteome as we provide a deep insight by identifying 4129 proteins and
      25503 peptides. The identified proteome defines the scope that enables PBMCs to
      be characterised as cellular major biomarker pool within the blood organ. 

PMID- 24724029
TI  - Does fatigue complaint reflect memory impairment in multiple sclerosis?
AB  - Background and Purpose. Fatigue and memory impairment are common symptoms in
      multiple sclerosis (MS) and both may interact with cognition. This can contribute
      to making a complaint misrepresentative of the objective disorder. We sought to
      determine whether fatigue complaint in MS reflects memory impairment and
      investigated whether patients' subjective fatigue is associated with memory
      complaint. Methods. Fifty MS patients complaining of fatigue underwent subjective
      assessment of fatigue and memory complaint measured using self-assessment scales.
      Cognitive functions were assessed using a battery of neuropsychological tests,
      including a test of verbal episodic memory, the selective reminding test (SRT).
      Correlations were studied between subjective fatigue, memory complaint, and
      performance in verbal episodic memory. Results. Depression score, psychotropic
      and/or antiepileptic drug use, Expanded Disability Status Scale (EDSS) score, and
      MS form were confounding factors. After adjusting for these confounding factors,
      neither fatigue complaint nor memory complaint was correlated with SRT
      performance. Subjective fatigue was significantly associated with memory
      complaint. Conclusion. Although complaint of fatigue in MS was correlated with
      memory complaint, subjective fatigue was not the expression of memory impairment.

PMID- 24724030
TI  - Anatomical considerations of the suprascapular nerve in rotator cuff repairs.
AB  - Introduction. When using the double interval slide technique for arthroscopic
      repair of chronic large or massive rotator cuff tears, the posterior interval
      release is directed toward the scapular spine until the fat pad that protects the
      suprascapular nerve is reached. Injury to the suprascapular nerve can occur due
      to the nerve's proximity to the operative field. This study aimed to identify
      safe margins for avoiding injury to the suprascapular nerve. Materials and
      Methods. For 20 shoulders in ten cadavers, the distance was measured from the
      suprascapular notch to the glenoid rim, the articular margin of the rotator cuff
      footprint, and the lateral border of the acromion. Results. From the
      suprascapular notch, the suprascapular nerve coursed an average of 3.42 cm to the
      glenoid rim, 5.34 cm to the articular margin of the rotator cuff footprint, and
      6.09 cm to the lateral border of the acromion. Conclusions. The results of this
      study define a safe zone, using anatomic landmarks, to help surgeons avoid
      iatrogenic injury to the suprascapular nerve when employing the double interval
      slide technique in arthroscopic repair of the rotator cuff. 

PMID- 24724031
TI  - Indications of brain computed tomography scan in children younger than 3 years of
      age with minor head trauma.
AB  - Objective. To investigate the indications to receive brain computed tomography
      (CT) scan and to define the pathological findings in children younger than three
      years of age with minor head trauma in emergency departments. Methods. In this
      study, hospital case notes of 1350 children attending the emergency department of
      Bitlis State Hospital between January 2011 and June 2013 were retrospectively
      reviewed. 508 children under 3 years of age with minor head trauma were included
      in this study. We also asked 37 physicians about the indications for requiring CT
      in these children. Results. This study included 508 children, 233 (45,9%) of whom
      were female and 275 were male. In 476 (93,7%) children, the brain CT was
      completely normal. 89,2% of physicians asked in the emergency department during
      that time interval reported that they requested CT scan to protect themselves
      against malpractice litigation. Conclusion. In infants and children with minor
      head trauma, most CT scans were unnecessary and the fear of malpractice
      litigation of physicians was the most common reason for requesting a CT. 

PMID- 24724032
TI  - In vitro cytotoxicity evaluation of four vital pulp therapy materials on l929
      fibroblasts.
AB  - The aim of this study was to evaluate cytotoxicity of direct pulp capping
      materials such as Dycal, Life, ProRoot MTA, and Super-Bond C&B on L929
      fibroblasts. Freshly mixed or set materials were prepared and eluted by
      incubation with cell culture medium for working time period (fresh) or for 6
      hours (set). The cells were exposed to media containing elutes for 24 hours,
      after which the cell survival was evaluated by MTS assays. In freshly mixed
      materials, average +/- standard deviation % cell viabilities were 40.2 +/- 14.0%,
      43.7 +/- 16.0%, 72.9 +/- 12.7%, and 66.0 +/- 13.6% for Dycal, Life, ProRoot MTA,
      and Super-Bond C&B, respectively. There was no statistical difference in cell
      viabilities among material groups, whereas in set materials, the cell viabilities
      were 48.7 +/- 14.8%, 37.2 +/- 10.6%, 46.7 +/- 15.2%, and 100 +/- 21.9% for Dycal,
      Life, ProRoot MTA, and Super-Bond C&B, respectively. Super-Bond C&B showed more
      cell viabilities than the other three material groups (P < 0.05). The four vital
      pulp therapy materials had similar cytotoxicity when the materials were fresh.
      Super-Bond C&B was less cytotoxic than Dycal, Life, and ProRoot MTA after the
      materials were set, which suggests the use of SB-C&B in future in vivo clinical
      investigations. 

PMID- 24724034
TI  - Antimicrobial Resistance of Salmonella enterica Isolates from Tonsil and Jejunum
      with Lymph Node Tissues of Slaughtered Swine in Metro Manila, Philippines.
AB  - Due to frequent antibiotic exposure, swine is now recognized as potential risk in
      disseminating drug-resistant Salmonella enterica strains. This study thus
      subjected 20 randomly selected S. enterica isolates from tonsil and jejunum with
      lymph node (JLN) tissues of swine slaughtered in Metro Manila, Philippines, to
      VITEK 2 antimicrobial susceptibility testing (AST). The test revealed all 20
      isolates had resistance to at least one antimicrobial agent, in which highest
      occurrence of resistance was to amikacin (100%), cefazolin (100%), cefuroxime
      (100%), cefuroxime axetil (100%), cefoxitin (100%), and gentamicin (100%),
      followed by ampicillin (50%), and then by sulfamethoxazole trimethoprim (30%).
      Three multidrug-resistant (MDR) isolates were detected. The sole S. enterica
      serotype Enteritidis isolate showed resistance to 12 different antibiotics
      including ceftazidime, ceftriaxone, amikacin, gentamicin, and tigecycline. This
      study is the first to report worldwide on the novel resistance to tigecycline of
      MDR S. enterica serotype Enteritidis isolated from swine tonsil tissues. This
      finding poses huge therapeutic challenge since MDR S. enterica infections are
      associated with increased rate of hospitalization or death. Thus, continual
      regulation of antimicrobial use in food animals and prediction of resistant
      serotypes are crucial to limit the spread of MDR S. enterica isolates among hogs
      and humans. 

PMID- 24724033
TI  - Oral and dental considerations in pediatric leukemic patient.
AB  - Throughout the world, there have been drastic decline in mortality rate in
      pediatric leukemic population due to early diagnosis and improvements in oncology
      treatment. The pediatric dentist plays an important role in the prevention,
      stabilization, and treatment of oral and dental problems that can compromise the
      child's health and quality of life during, and follow up of the cancer treatment.
      This manuscript discusses recommendations and promotes dental care of the
      pediatric leukemic patients. 

PMID- 24724035
TI  - A New Predictive Index for Osteoporosis in Men under 70 Years of Age: An Index to
      Identify Male Candidates for Osteoporosis Screening by Bone Mineral Density.
AB  - Background. Bone mineral density (BMD) screening guidelines for osteoporosis in
      men seem to have remained unclear. We aimed to set up a predictive index for the
      osteoporosis(PIO) in men under 70 years of age and present the optimal cutoff
      value of it, so that clinicians might use it to identify male candidates who
      benefit from taking the BMD screening. Methods. Adult men under 70 years old who
      met certain criteria were included. With the determined significant predictors
      for osteoporosis, we created a new index that presumably best predicts the
      osteoporosis and compared the predictability of it to other variables. Lastly,
      the optimal cutoff value of the PIO was calculated. Results. A total of 359 men
      were included. Age, weight, and current smoking status turned out to be
      significant predictors for osteoporosis. The PIO was as follows: [age(years) + 10
      (for current smoker)]/weight(kg). Compared to other variables, the PIO showed the
      greatest predictive performance with the optimal cutoff point being 0.87 at which
      sensitivity and specificity were 71.9% and 70.0%, respectively. Conclusion. A new
      predictive index appeared to predict the presence of osteoporosis fairly well and
      thus can be used with its cutoff point to identify men under 70 years of age who
      need BMD screening. 

PMID- 24724036
TI  - Utilizing fast spin echo MRI to reduce image artifacts and improve implant/tissue
      interface detection in refractory Parkinson's patients with deep brain
      stimulators.
AB  - Introduction. In medically refractory Parkinson's disease (PD) deep-brain
      stimulation (DBS) is an effective therapeutic tool. Postimplantation MRI is
      important in assessing tissue damage and DBS lead placement accuracy. We wanted
      to identify which MRI sequence can detect DBS leads with smallest artifactual
      signal void, allowing better tissue/electrode edge conspicuity. Methods. Using an
      IRB approved protocol 8 advanced PD patients were imaged within MR conditional
      safety guidelines at low RF power (SAR <= 0.1 W/kg) in coronal plane at 1.5T by
      various sequences. The image slices were subjectively evaluated for diagnostic
      quality and the lead contact diameters were compared to identify a sequence least
      affected by metallic leads. Results and Discussion. Spin echo and fast spin echo
      based low SAR sequences provided acceptable image quality with comparable image
      blooming (enlargement) of stimulator leads. The mean lead diameters were 2.2 +/-
      0.1 mm for 2D, 2.1 +/- 0.1 mm for 3D, and 4.0 +/- 0.2 mm for 3D MPRAGE sequence.
      Conclusion. Low RF power spin echo and fast spin echo based 2D and 3D FSE
      sequences provide acceptable image quality adjacent to DBS leads. The smallest
      artifactual blooming of stimulator leads is present on 3D FSE while the largest
      signal void appears in the 3D MPRAGE sequence. 

PMID- 24724037
TI  - Quantitative electromyographic analysis of reaction time to external auditory
      stimuli in drug-naive Parkinson's disease.
AB  - Evaluation of motor symptoms in Parkinson's disease (PD) is still based on
      clinical rating scales by clinicians. Reaction time (RT) is the time interval
      between a specific stimulus and the start of muscle response. The aim of this
      study was to identify the characteristics of RT responses in PD patients using
      electromyography (EMG) and to elucidate the relationship between RT and clinical
      features of PD. The EMG activity of 31 PD patients was recorded during isometric
      muscle contraction. RT was defined as the time latency between an auditory beep
      and responsive EMG activity. PD patients demonstrated significant delays in both
      initiation and termination of muscle contraction compared with controls. Cardinal
      motor symptoms of PD were closely correlated with RT. RT was longer in more
      affected side and in more-advanced PD stages. Frontal cognitive function, which
      is indicative of motor programming and movement regulation and perseveration, was
      also closely related with RT. In conclusion, greater RT is the characteristic
      motor features of PD and it could be used as a sensitive tool for motor function
      assessment in PD patients. Further investigations are required to clarify the
      clinical impact of the RT on the activity of daily living of patients with PD. 

PMID- 24724038
TI  - Predictors of in-hospital mortality for stroke in douala, cameroon.
AB  - Background. The objective of this study was to describe complications in
      hospitalized patients for stroke and to determine the predictive factors of
      intrahospital mortality from stroke at the Douala General Hospital (DGH) in
      Cameroon. Patients and Methods. A prospective cross-sectional study was carried
      out from January 1, 2010 to December 31, 2012, at the DGH. All the patients who
      were aged more than 15 years with established diagnosis of stroke were included.
      A univariate analysis was done to look for factors associated with the risk of
      death, whilst the predictive factors of death were determined in a multivariate
      analysis following Cox regression model. Results. Of the 325 patients included
      patients, 68.1% were males and the mean age was 58.66 +/- 13.6 years. Ischaemic
      stroke accounted for 52% of the cases. Sepsis was the leading complications
      present in 99 (30.12%) cases. Independent predicting factors of in-hospital
      mortality were Glasgow Coma Scale lower than 8 (HR = 2.17 95% CI 4.86-36.8; P =
      0.0001), hyperglycaemia at admission (HR = 3.61 95% CI 1.38-9.44; P = 0.009), and
      hemorrhagic stroke (HR = 5.65 95% CI 1.77-18; P = 0.003). Conclusion. The
      clinician should systematically diagnose and treat infectious states and
      hyperglycaemia in stroke. 

PMID- 24724039
TI  - Blastomyces dermatitidis: Antibody Detection in Sera from Dogs with Blastomycosis
      with Yeast Lysate Antigens Produced from Human and Dog Isolates.
AB  - Dogs are common hosts to the fungal organism Blastomyces dermatitidis, which
      causes the systemic disease blastomycosis. The goal of our study was to compare
      the reactivity of two B. dermatitidis yeast lysate antigens prepared from dog
      isolates (ERC-2, Wisconsin; T-58, Tennessee) and two lysate antigens prepared
      from human isolates (B5931 and B5896, Minnesota) against 48 serum specimens from
      dogs with confirmed blastomycosis using the indirect enzyme-linked immunosorbent
      assay (ELISA). Secondarily, we used three different ELISA substrates (Ultra TMB:
      A, SureBlue: B, and SureBlue Reserve: C) to compare the effectiveness of each
      substrate. Mean absorbance values ranged from 0.446 (B) to 0.651 (C) for the
      B5931 antigen and from 0.393 (B) to 0.540 (C) for the ERC-2 antigen in Trial 1.
      In Trial 2, the absorbance values ranged from 0.628 (B) to 0.909 (A) for the
      B5896 antigen and from 0.828 (B) to 1.375 (C) for the T-58 antigen. In Trial 1,
      the lysate antigen prepared from the human isolate B5931 exhibited the highest
      absorbance value and in Trial 2 the lysate prepared from the dog isolate T-58 was
      the most reactive. The overall results thus indicated that the T-58 lysate was
      the optimal reagent when used to detect antibody with the Sure-Blue Reserve
      substrate. Our laboratory is continuing to study B. dermatitidis antigen and
      substrate combinations for the reliable immunodiagnosis of blastomycosis in
      humans and animals. 

PMID- 24724040
TI  - Determination of Polyphenol Components of Korean Prostrate Spurge (Euphorbia
      supina) by Using Liquid Chromatography-Tandem Mass Spectrometry: Overall
      Contribution to Antioxidant Activity.
AB  - The Korean prostrate spurge Euphorbia supina is a weed that has been used in folk
      medicine in Korea against a variety of diseases. Nine polyphenols were
      characterized for this plant by using high-performance liquid chromatography
      tandem mass spectrometry (HPLC-MS/MS) and the results were compared with the
      literature data. The individual components were validated using the calibration
      curves of structurally related external standards and quantified for the first
      time by using the validated method. Correlation coefficients (r (2)) were
      >0.9907. The limit of detection and limit of quantification of the method were
      >0.028 mg/L and 0.094 mg/L, respectively. Recoveries measured at 50 mg/L and 100
      mg/L were 76.1-102.8% and 85.2-98.6%, respectively. The total amount of the
      identified polyphenols was 3352.9 +/- 2.8 mg/kg fresh plant. Quercetin and
      kaempferol derivatives formed 84.8% of the total polyphenols. The antioxidant
      activities of the flavonoids were evaluated in terms of 1,1-diphenyl-2
      picrylhydrazyl and 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) radical
      cation-scavenging activity, and the reducing power showed a dose-dependent
      increase. Cell viability was effectively suppressed at polyphenol mixture
      concentrations >250 mg/L. 

PMID- 24724041
TI  - Position-Based Virtual Fixtures for Membrane Peeling with a Handheld
      Micromanipulator.
AB  - Peeling delicate retinal membranes, which are often less than 5 um thick, is one
      of the most challenging retinal surgeries. Preventing rips and tears caused by
      tremor and excessive force can decrease injury and reduce the need for follow up
      surgeries. We propose the use of a fully handheld microsurgical robot to suppress
      tremor while enforcing helpful constraints on the motion of the tool. Using
      stereo vision and tracking algorithms, the robot activates motion-scaled behavior
      as the tip reaches the surface, providing finer control during the critical step
      of engaging the membrane edge. A hard virtual fixture just below the surface
      limits the total downward force that can be applied. Furthermore, velocity
      limiting during the peeling helps the surgeon maintain a smooth, constant force
      while lifting and delaminating the membrane. On a phantom consisting of plastic
      wrap stretched across a rubber slide, we demonstrate our approach reduces maximum
      force by 40-70%.

PMID- 24724042
TI  - A Comparative White Matter Study with Parkinson's disease, Parkinson's Disease
      with Dementia and Alzheimer's Disease.
AB  - Alzheimer's disease (AD) and Parkinson's disease (PD) are among the most common
      neurodegenerative disorders affecting older populations. AD is characterized by
      impaired memory and cognitive decline while the primary symptoms of PD include
      resting tremor, bradykinesia and rigidity. In PD, mild cognitive changes are
      frequently present, which could progress to dementia (PD dementia (PDD)). PDD and
      AD dementias are different in pathology although the difference in
      microstructural changes remains unknown. To further understand these diseases, it
      is essential to understand the distinct mechanism of their microstructural
      changes. We used diffusion tensor imaging (DTI) to investigate white matter tract
      differences between early stage individuals with AD (n=14), PD (n=12), PDD (n=9),
      and healthy non-demented controls (CON) (n=13). We used whole brain tract based
      spatial statistics (TBSS) and a region of interest (ROI) analysis focused on the
      substantia nigra (SN). We found that individuals with PDD had more widespread
      white matter degeneration compared to PD, AD, and CON. Individuals with AD had
      few regional abnormalities in the anterior and posterior projections of the
      corpus callosum while PD and CON did not appear to have significant white matter
      degeneration when compared to other groups. ROI analyses showed that PDD had the
      highest diffusivity in the SN and were significantly different from CON. There
      were no significant ROI differences between CON, PD, or AD. In conclusion, global
      white matter microstructural deterioration is evident in individuals with PDD,
      and DTI may provide a means with which to tease out pathological differences
      between AD and PD dementias.

PMID- 24724043
TI  - Diffuse Correlation Spectroscopy (DCS) for Assessment of Tissue Blood Flow in
      Skeletal Muscle: Recent Progress.
AB  - Near-infrared diffuse correlation spectroscopy (DCS) is an emerging technology
      for monitoring blood flow in various tissues. This article reviews the recent
      progress of DCS for the assessment of skeletal muscle blood flow, including the
      developments in technology allowing use during dynamic exercise and muscular
      electrical stimulation, the utilization for diagnosis of muscle vascular
      diseases, and the applications for evaluating treatment effects. The limitations
      of current DCS studies and future perspective are finally discussed.

PMID- 24724044
TI  - Nanosponge formation from organocatalytically-synthesized poly(carbonate)
      copoplymers.
AB  - Advanced organocatalytic synthesis methods were employed to prepare linear
      poly(carbonate)s with control over functional group incorporation and molecular
      weight. Pendant allyl or epoxide groups served as reaction partners in thiol-ene
      click or epoxide-amine reactions with ethylene oxide-containing crosslinking
      groups to form a panel of six novel poly(carbonate) nanosponges with crosslinking
      densities ranging from 5%, 10% and 20% via an intermolecular chain-crosslinking
      approach.

PMID- 24724045
TI  - Treatment outcome of ductal carcinoma in situ patients treated with postoperative
      radiation therapy.
AB  - PURPOSE: To evaluate the outcome of ductal carcinoma in situ (DCIS) patients who
      underwent surgery followed by radiation therapy (RT). MATERIALS AND METHODS: We
      retrospectively reviewed 106 DCIS patients who underwent surgery followed by
      postoperative RT between 1994 and 2006. Ninety-four patients underwent breast
      conserving surgery, and mastectomy was performed in 12 patients due to extensive
      DCIS. Postoperative RT was delivered to whole breast with 50.4 Gy/28 fx. Tumor
      bed boost was offered to 7 patients (6.6%). Patients with hormonal receptor
      positive tumors were treated with hormonal therapy. RESULTS: The median follow-up
      duration was 83.4 months (range, 33.4 to 191.5 months) and the median age was
      47.8 years. Ten patients (9.4%) had resection margin <1 mm and high-grade and
      estrogen receptor-negative tumors were observed in 39 (36.8%) and 20 (18.9%)
      patients, respectively. The 7-year ipsilateral breast tumor recurrence (IBTR)
      free survival rate was 95.3%. Resection margin (<1 or >=1 mm) was the significant
      prognostic factor for IBTR in univariate and multivariate analyses (p < 0.001 and
      p = 0.016, respectively). CONCLUSION: Postoperative RT for DCIS can achieve
      favorable treatment outcome. Resection margin was the important prognostic factor
      for IBTR in the DCIS patients who underwent postoperative RT.

PMID- 24724046
TI  - Postoperative radiotherapy dose correlates with locoregional control in patients
      with extra-hepatic bile duct cancer.
AB  - PURPOSE: To evaluate the results of postoperative radiotherapy in patients with
      extra-hepatic bile duct cancer (EHBDC) and identify the prognostic factors for
      local control and survival. MATERIALS AND METHODS: Between January 2001 and
      December 2010, we retrospectively reviewed the cases of 70 patients with EHBDC
      who had undergone curative resection and received postoperative radiotherapy. The
      median radiation dose was 50.4 Gy (range, 41.4 to 54 Gy). The resection margin
      status was R0 in 30 patients (42.9%), R1 in 25 patients (35.7%), and R2 in 15
      patients (21.4%). RESULTS: The 5-year rates of overall survival (OS), event-free
      survival (EFS), and locoregional control (LRC) for all patients were 42.9%,
      38.3%, and 61.2%, respectively. The major pattern of failure was distant relapses
      (33 patients, 47.1%). A multivariate analysis showed that the postradiotherapy
      CA19-9 level, radiation dose (>=50 Gy), R2 resection margins, perineural
      invasion, and T stage were the significant prognostic factors for OS, EFS, and
      LRC. OS was not significantly different between the patients receiving R0 and R1
      resections, but was significantly lower among those receiving R2 resection
      (54.6%, 56.1%, and 7.1% for R0, R1, and R2 resections, respectively). CONCLUSION:
      In patients with EHBDC who had undergone curative resection, a postoperative
      radiotherapy dose less than 50 Gy was suboptimal for OS and LRC. Higher radiation
      doses may be needed to obtain better LRC. Further investigation of novel therapy
      or palliative treatment should be considered for patients receiving R2 resection.

PMID- 24724047
TI  - Transcatheter arterial chemoembolization and radiation therapy for treatment
      naive patients with locally advanced hepatocellular carcinoma.
AB  - PURPOSE: To evaluate the safety and efficacy of transcatheter arterial
      chemoembolization (TACE) followed by radiotherapy (RT) in treatment-naive
      patients with locally advanced hepatocellular carcinoma (HCC). MATERIALS AND
      METHODS: ELIGIBILITY CRITERIA WERE AS FOLLOWS: newly diagnosed with HCC, the
      Barcelona Clinic Liver Cancer stage C, Child-Pugh class A or B, and no prior
      treatment for HCC. Patients with extrahepatic spread were excluded. A total of 59
      patients were retrospectively enrolled. All patients were treated with TACE
      followed by RT. The time interval between TACE and RT was 2 weeks as per
      protocol. A median RT dose was 47.25 Gy10 as the biologically effective dose
      using the alpha/beta = 10 (range, 39 to 65.25 Gy10). RESULTS: At 1 month,
      complete response was obtained in 3 patients (5%), partial response in 27
      patients (46%), stable disease in 13 patients (22%), and progressive disease in
      16 patients (27%). The actuarial one- and two-year OS rates were 60.1% and 47.2%,
      respectively. The median OS was 17 months (95% confidence interval, 5.6 to 28.4
      months). The median time to progression was 4 months (range, 1 to 35 months).
      Grade 3 or greater liver enzyme elevation occurred in only two patients (3%)
      after RT. Grade 3 gastroduodenal toxicity developed in two patients (3%).
      CONCLUSION: The combination treatment of TACE followed by RT with two-week
      interval was safe and it showed favorable outcomes in treatment-naive patients
      with locally advanced HCC. A prospective randomized trial is needed to validate
      these results.

PMID- 24724048
TI  - A predictive model to guide management of the overlap region between target
      volume and organs at risk in prostate cancer volumetric modulated arc therapy.
AB  - PURPOSE: The goal of this study is to determine whether the magnitude of overlap
      between planning target volume (PTV) and rectum (Rectumoverlap) or PTV and
      bladder (Bladderoverlap) in prostate cancer volumetric-modulated arc therapy
      (VMAT) is predictive of the dose-volume relationships achieved after
      optimization, and to identify predictive equations and cutoff values using these
      overlap volumes beyond which the Quantitative Analyses of Normal Tissue Effects
      in the Clinic (QUANTEC) dose-volume constraints are unlikely to be met. MATERIALS
      AND METHODS: Fifty-seven patients with prostate cancer underwent VMAT planning
      using identical optimization conditions and normalization. The PTV (for the 50.4
      Gy primary plan and 30.6 Gy boost plan) included 5 to 10 mm margins around the
      prostate and seminal vesicles. Pearson correlations, linear regression analyses,
      and receiver operating characteristic (ROC) curves were used to correlate the
      percentage overlap with dose-volume parameters. RESULTS: The percentage
      Rectumoverlap and Bladderoverlap correlated with sparing of that organ but
      minimally impacted other dose-volume parameters, predicted the primary plan
      rectum V45 and bladder V50 with R(2) = 0.78 and R(2) = 0.83, respectively, and
      predicted the boost plan rectum V30 and bladder V30 with R(2) = 0.53 and R(2) =
      0.81, respectively. The optimal cutoff value of boost Rectumoverlap to predict
      rectum V75 >15% was 3.5% (sensitivity 100%, specificity 94%, p < 0.01), and the
      optimal cutoff value of boost Bladderoverlap to predict bladder V80 >10% was 5.0%
      (sensitivity 83%, specificity 100%, p < 0.01). CONCLUSION: The degree of overlap
      between PTV and bladder or rectum can be used to accurately guide physicians on
      the use of interventions to limit the extent of the overlap region prior to
      optimization.

PMID- 24724049
TI  - PET/CT planning during chemoradiotherapy for esophageal cancer.
AB  - PURPOSE: To evaluate the usefulness of positron emission tomography/computed
      tomography (PET/CT) for field modification during radiotherapy in esophageal
      cancer. MATERIALS AND METHODS: We conducted a retrospective study on 33 patients
      that underwent chemoradiotherapy (CRT). Pathologic findings were squamous cell
      carcinoma in 32 patients and adenocarcinoma in 1 patient. All patients underwent
      PET/CT scans before and during CRT (after receiving 40 Gy and before a 20 Gy
      boost dose). Response evaluation was determined by PET/CT using metabolic tumor
      volume (MTV), total glycolytic activity (TGA), MTV ratio (rMTV) and TGA ratio
      (rTGA), or determined by CT. rMTV and rTGA were reduction ratio of MTV and TGA
      between before and during CRT, respectively. RESULTS: Significant decreases in
      MTV (MTV2.5: mean 70.09%, p < 0.001) and TGA (TGA2.5: mean 79.08%, p<0.001) were
      found between before and during CRT. Median rMTV2.5 was 0.299 (range, 0 to 0.98)
      and median rTGA2.5 was 0.209 (range, 0 to 0.92). During CRT, PET/CT detected
      newly developed distant metastasis in 1 patient, and this resulted in a treatment
      strategy change. At a median 4 months (range, 0 to 12 months) after completion of
      CRT, 8 patients (24.2%) achieved clinically complete response, 11 (33.3%) partial
      response, 5 (15.2%) stable disease, and 9 (27.3%) disease progression. SUVmax (p
      = 0.029), rMTV50% (p = 0.016), rMTV75% (p = 0.023) on intra-treatment PET were
      found to correlate with complete clinical response. CONCLUSION: PET/CT during CRT
      can provide additional information useful for radiotherapy planning and offer the
      potential for tumor response evaluation during CRT. rMTV50% during CRT was found
      to be a useful predictor of clinical response.

PMID- 24724050
TI  - CT-based quantitative evaluation of radiation-induced lung fibrosis: a study of
      interobserver and intraobserver variations.
AB  - PURPOSE: The degree of radiation-induced lung fibrosis (RILF) can be measured
      quantitatively by fibrosis volume (VF) on chest computed tomography (CT) scan.
      The purpose of this study was to investigate the interobserver and intraobserver
      variability in CT-based measurement of VF. MATERIALS AND METHODS: We selected 10
      non-small cell lung cancer patients developed with RILF after postoperative
      radiation therapy (PORT) and delineated VF on the follow-up chest CT scanned at
      more than 6 months after radiotherapy. Three radiation oncologists independently
      delineated VF to investigate the interobserver variability. Three times of
      delineation of VF was performed by two radiation oncologists for the analysis of
      intraobserver variability. We analysed the concordance index (CI) and
      inter/intraclass correlation coefficient (ICC). RESULTS: The median CI was 0.61
      (range, 0.44 to 0.68) for interobserver variability and the median CIs for
      intraobserver variability were 0.69 (range, 0.65 to 0.79) and 0.61(range, 0.55 to
      0.65) by two observers. The ICC for interobserver variability was 0.974 (p <
      0.001) and ICCs for intraobserver variability were 0.996 (p < 0.001) and 0.991 (p
      < 0.001), respectively. CONCLUSION: CT-based measurement of VF with patients who
      received PORT was a highly consistent and reproducible quantitative method
      between and within observers.

PMID- 24724052
TI  - Culture models to define key mediators of cancer matrix remodeling.
AB  - High grade serous epithelial ovarian cancer (HG-SOC) is one of the most
      devastating gynecological cancers affecting women worldwide, with a poor survival
      rate despite clinical treatment advances. HG-SOC commonly metastasizes within the
      peritoneal cavity, primarily to the mesothelial cells of the omentum, which
      regulate an extracellular matrix rich in collagens type I, III, and IV along with
      laminin, vitronectin, and fibronectin. Cancer cells depend on their ability to
      penetrate and invade secondary tissue sites to spread, however a detailed
      understanding of the molecular mechanisms underlying these processes remain
      largely unknown. Given the high metastatic potential of HG-SOC and the associated
      poor clinical outcome, it is extremely important to identify the pathways and the
      components of which that are responsible for the progression of this disease. In
      vitro methods of recapitulating human disease processes are the critical first
      step in such investigations. In this context, establishment of an in vitro "tumor
      like" micro-environment, such as 3D culture, to study early disease and
      metastasis of human HG-SOC is an important and highly insightful method. In
      recent years, many such methods have been established to investigate the adhesion
      and invasion of human ovarian cancer cell lines. The aim of this review is to
      summarize recent developments in ovarian cancer culture systems and their use to
      investigate clinically relevant findings concerning the key players in driving
      human HG-SOC. 

PMID- 24724051
TI  - Current concepts in pediatric Philadelphia chromosome-positive acute
      lymphoblastic leukemia.
AB  - The t(9;22)(q34;q11) or Philadelphia chromosome creates a BCR-ABL1 fusion gene
      encoding for a chimeric BCR-ABL1 protein. It is present in 3-4% of pediatric
      acute lymphoblastic leukemia (Ph(+) ALL), and about 25% of adult ALL cases. Prior
      to the advent of tyrosine kinase inhibitors (TKI), Ph(+) ALL was associated with
      a very poor prognosis despite the use of intensive chemotherapy and frequently
      hematopoietic stem-cell transplantation (HSCT) in first remission. The
      development of TKIs revolutionized the therapy of Ph(+) ALL. Addition of the
      first generation ABL1 class TKI imatinib to intensive chemotherapy dramatically
      increased the survival for children with Ph(+) ALL and established that many
      patients can be cured without HSCT. In parallel, the mechanistic understanding of
      Ph(+) ALL expanded exponentially through careful mapping of pathways downstream
      of BCR-ABL1, the discovery of mutations in master regulators of B-cell
      development such as IKZF1 (Ikaros), PAX5, and early B-cell factor (EBF), the
      recognition of the complex clonal architecture of Ph(+) ALL, and the delineation
      of genomic, epigenetic, and signaling abnormalities contributing to relapse and
      resistance. Still, many important basic and clinical questions remain unanswered.
      Current clinical trials are testing second generation TKIs in patients with newly
      diagnosed Ph(+) ALL. Neither the optimal duration of therapy nor the optimal
      chemotherapy backbone are currently defined. The role of HSCT in first remission
      and post-transplant TKI therapy also require further study. In addition, it will
      be crucial to continue to dig deeper into understanding Ph(+) ALL at a
      mechanistic level, and translate findings into complementary targeted approaches.
      Expanding targeted therapies hold great promise to decrease toxicity and improve
      survival in this high-risk disease, which provides a paradigm for how targeted
      therapies can be incorporated into treatment of other high-risk leukemias. 

PMID- 24724053
TI  - Sweet and sour: the impact of differential glycosylation in cancer cells
      undergoing epithelial-mesenchymal transition.
AB  - Glycosylation changes are a feature of disease states. One clear example is
      cancer cells, which commonly express glycans at atypical levels or with different
      structural attributes than those found in normal cells. Epithelial-mesenchymal
      transition (EMT) was initially recognized as an important step for morphogenesis
      during embryonic development, and is now shown to be one of the key steps
      promoting tumor metastasis. Cancer cells undergoing EMT are characterized by
      significant changes in glycosylation of the extracellular matrix (ECM) components
      and cell-surface glycoconjugates. Current scientific methodology enables all
      hallmarks of EMT to be monitored in vitro and this experimental model has been
      extensively used in oncology research during the last 10 years. Several studies
      have shown that cell-surface carbohydrates attached to proteins through the amino
      acids, serine, or threonine (O-glycans), are involved in tumor progression and
      metastasis, however, the impact of O-glycans on EMT is poorly understood. Recent
      studies have demonstrated that transforming growth factor-beta (TGF-beta), a
      known EMT inducer, has the ability to promote the up-regulation of a site
      specific O-glycosylation in the IIICS domain of human oncofetal fibronectin, a
      major ECM component expressed by cancer cells and embryonic tissues. Armed with
      the knowledge that cell-surface glycoconjugates play a major role in the
      maintenance of cell homeostasis and that EMT is closely associated with
      glycosylation changes, we may benefit from understanding how unusual glycans can
      govern the molecular pathways associated with cancer progression. This review
      initially focuses on some well-known changes found in O-glycans expressed by
      cancer cells, and then discusses how these alterations may modulate the EMT
      process. 

PMID- 24724054
TI  - The many faces of neuroendocrine differentiation in prostate cancer progression.
AB  - In normal prostate, neuroendocrine (NE) cells are rare and interspersed among the
      epithelium. These cells are believed to provide trophic signals to epithelial
      cell populations through the secretion of an abundance of neuropeptides that can
      diffuse to influence surrounding cells. In the setting of prostate cancer (PC),
      NE cells can also stimulate surrounding prostate adenocarcinoma cell growth, but
      in some cases adenocarcinoma cells themselves acquire NE characteristics. This
      epithelial plasticity is associated with decreased androgen receptor (AR)
      signaling and the accumulation of neuronal and stem cell characteristics.
      Transformation to an NE phenotype is one proposed mechanism of resistance to
      contemporary AR-targeted treatments, is associated with poor prognosis, and
      thought to represent up to 25% of lethal PCs. Importantly, the advent of high
      throughput technologies has started to provide clues for understanding the
      complex molecular profiles of tumors exhibiting NE differentiation. Here, we
      discuss these recent advances, the multifaceted manner by which an NE-like state
      may arise during the different stages of disease progression, and the potential
      benefit of this knowledge for the management of patients with advanced PC. 

PMID- 24724056
TI  - HIV risk behaviors differ by workplace stability among Mexican female sex workers
      with truck driver clientele.
AB  - BACKGROUND: In a study of female sex workers (FSW) servicing truck driver clients
      in Mexican border cities, we evaluated differences in HIV/STI risk behaviors by
      workplace. DESIGN AND METHODS: Our study was cross-sectional and its population
      comprised 100 FSWs from Nuevo Laredo (US border) and 100 FSWs from Ciudad Hidalgo
      (Guatemalan border). The main outcome was primary place of sex work defined as
      unstable (street, vehicle, gas station, etc.) vs stable (bar, brothel, and
      hotel). Logistic regression was used to identify correlates associated with
      trading sex at unstable workplaces in the last month. RESULTS: Of the FSW
      surveyed, 18% reported an unstable workplace. The majority of FSW surveyed were
      young (<30), single, had <9th grade education, and had worked in the sex trade
      for a median of 4.9 years. After controlling for study site, FSW with unstable
      vs. stable workplaces were more likely to have a majority/all truck driver
      clientele, but were less likely to have visited a gynecologist in the last year
      (OR 0.1, 95%CI 0.03-0.4) or ever had an HIV test (OR 0.1, 95%CI 0.06-0.3), and
      there was a trend towards lower condom use self-efficacy scores (OR 0.8 per unit
      increase, 95%CI 0.7-1.0). On multivariate regression, unstable workplace was
      associated with having majority/all truck driver clientele, being surveyed in
      Nuevo Laredo, and decreased odds of ever having an HIV test. CONCLUSIONS: Among
      Mexican FSW with truck driver clients, providing safe indoor spaces for sex work
      may help facilitate public health interventions that improve HIV/STI and
      reproductive health outcomes.

PMID- 24724057
TI  - Mantle cell lymphoma: a model for risk-adapted treatment approach.

PMID- 24724058
TI  - How do we prepare ourselves for a new paradigm of medicine to advance the
      treatment of pediatric acute lymphoblastic leukemia?

PMID- 24724059
TI  - Leptomeningeal involvement in CLL.

PMID- 24724055
TI  - Mechanisms of post-transcriptional gene regulation in bacterial biofilms.
AB  - Biofilms are characterized by a dense multicellular community of microorganisms
      that can be formed by the attachment of bacteria to an inert surface and to each
      other. The development of biofilm involves the initial attachment of planktonic
      bacteria to a surface, followed by replication, cell-to-cell adhesion to form
      microcolonies, maturation, and detachment. Mature biofilms are embedded in a self
      produced extracellular polymeric matrix composed primarily of bacterial-derived
      exopolysaccharides, specialized proteins, adhesins, and occasionally DNA. Because
      the synthesis and assembly of biofilm matrix components is an exceptionally
      complex process, the transition between its different phases requires the
      coordinate expression and simultaneous regulation of many genes by complex
      genetic networks involving all levels of gene regulation. The finely controlled
      intracellular level of the chemical second messenger molecule, cyclic-di-GMP is
      central to the post-transcriptional mechanisms governing the switch between the
      motile planktonic lifestyle and the sessile biofilm forming state in many
      bacteria. Several other post-transcriptional regulatory mechanisms are known to
      dictate biofilm development and assembly and these include RNA-binding proteins,
      small non-coding RNAs, toxin-antitoxin systems, riboswitches, and RNases. Post
      transcriptional regulation is therefore a powerful molecular mechanism employed
      by bacteria to rapidly adjust to the changing environment and to fine tune gene
      expression to the developmental needs of the cell. In this review, we discuss
      post-transcriptional mechanisms that influence the biofilm developmental cycle in
      a variety of pathogenic bacteria. 

PMID- 24724060
TI  - Hemophagocytosis in the pleural fluid of a patient with hemophagocytic
      lymphohistiocytosis.

PMID- 24724061
TI  - Disease modeling and cell based therapy with iPSC: future therapeutic option with
      fast and safe application.
AB  - Induced pluripotent stem cell (iPSC) technology has shown us great hope to treat
      various human diseases which have been known as untreatable and further endows
      personalized medicine for future therapy without ethical issues and immunological
      rejection which embryonic stem cell (hES) treatment has faced. It has been agreed
      that iPSCs knowledge can be harnessed from disease modeling which mimics human
      pathological development rather than trials utilizing conventional rodent and
      cell lines. Now, we can routinely generate iPSC from patient specific cell
      sources, such as skin fibroblast, hair follicle cells, patient blood samples and
      even urine containing small amount of epithelial cells. iPSC has both similarity
      and dissimilarity to hES. iPSC is similar enough to regenerate tissue and even
      full organism as ES does, however what we want for therapeutic advantage is
      limited to regenerated tissue and lineage specific differentiation. Depending on
      the lineage and type of cells, both tissue memory containing (DNA
      rearrangement/epigenetics) and non-containing iPSC can be generated. This makes
      iPSC even better choice to perform disease modeling as well as cell based
      therapy. Tissue memory containing iPSC from mature leukocytes would be beneficial
      for curing cancer and infectious disease. In this review, the benefit of iPSC for
      translational approaches will be presented. 

PMID- 24724063
TI  - Characteristics of hematologic malignancies with coexisting t(9;22) and inv(16)
      chromosomal abnormalities.
AB  - BACKGROUND: The coexistence of t(9;22)(q34;q11.2) and inv(16)(p13q22) chromosomal
      abnormalities is extremely uncommon, and only a small number of such cases have
      been reported. Here, we characterized 7 cases of hematologic malignancy
      exhibiting t(9;22) and inv(16) coexistence. METHODS: We reviewed the cytogenetic
      data for hematologic malignancies treated at the Catholic Blood and Marrow
      Transplantation Center between January 2004 and June 2013. We identified 7 cases
      exhibiting t(9;22) and inv(16) coexistence. In addition, we analyzed mutations in
      the IKZF1, NPM1, FLT3, N-RAS, K-RAS, c-KIT, and TP53 genes. RESULTS: Four cases
      of chronic myelogenous leukemia (CML; 1 chronic phase, 2 accelerated phase, and 1
      blast phase) and 3 cases of acute myeloid leukemia (AML; 1 de novo and 2 therapy
      related) were identified. The percentages of circulating blasts and bone marrow
      eosinophils were higher in AML cases than in CML cases (53% vs. 5% and 30% vs.
      5.5%, respectively). The proportions of each chromosomal abnormality were used
      along with follow-up karyotyping results to identify secondary changes. In
      BCR/ABL, a p210 fusion transcript was associated with CML, whereas a p190 fusion
      transcript was associated with AML. One patient with AML harbored 2 mutations: c
      KIT D816V and TP53 E11Q. All patients except 1 with CML blast phase sustained
      clinical remission after treatment, which included an imatinib mesylate regimen.
      CONCLUSION: This study shows that observations of bone marrow morphology, initial
      and follow-up cytogenetic studies, and karyotyping of BCR/ABL1 and CBFB/MYH11
      provide valuable information for characterizing hematologic malignancies
      exhibiting t(9;22) and inv(16) coexistence.

PMID- 24724062
TI  - Clinical features and treatment outcomes in patients with mantle cell lymphoma in
      Korea: Study by the Consortium for Improving Survival of Lymphoma.
AB  - BACKGROUND: We investigated the clinical features and treatment outcomes of
      patients with mantle cell lymphoma (MCL) in Korea. METHODS: We retrospectively
      analyzed the clinical characteristics and prognosis of 131 patients diagnosed
      with MCL between January 2004 and December 2009 at 15 medical centers in Korea;
      all patients received at least 1 chemotherapeutic regimen for MCL. RESULTS: The
      median age for the patients was 63 years (range, 26-78 years), and 77.9% were
      men. A total of 105 patients (80.1%) had stage III or IV MCL at diagnosis. Fifty
      two patients (39.7%) were categorized with high- or high-intermediate risk MCL
      according to the International Prognostic Index (IPI). Eighteen patients (13.7%)
      were in the high-risk group according to the simplified MCL-IPI (MIPI). The
      overall incidence of extranodal involvement was 69.5%. The overall incidence of
      bone marrow and gastrointestinal involvements at diagnosis was 41.2% and 35.1%,
      respectively. Cyclophosphamide, doxorubicin, vincristine, prednisolone, and
      rituximab were used frequently as the first-line treatment (41.2%). With a median
      follow-up duration of 20.0 months (range, 0.2-77.0 months), the overall survival
      (OS) at 2 years was 64.7%, while the event-free survival (EFS) was 39.7%.
      Multivariate analysis showed that the simplified MIPI was significantly
      associated with OS. However, the use of a rituximab-containing regimen was not
      associated with OS and EFS. CONCLUSION: Similar to results from Western
      countries, the current study found that simplified MIPI was an important
      prognostic factor in Korean patients with MCL.

PMID- 24724064
TI  - Childhood acute lymphoblastic leukemia with hyperleukocytosis at presentation.
AB  - BACKGROUND: Hyperleukocytosis caused by acute lymphoblastic leukemia (ALL) is
      associated with early morbidity and mortality due to hyperviscosity arising from
      the excessive number of leukocytes.This study was designed to assess the
      incidence of hyperleukocytosis, survival outcomes, and adverse features among
      pediatric ALL patients with hyperleukocytosis. METHODS: Between January 2001 and
      December 2010, 104 children with previously untreated ALL were enrolled at the
      Pusan National University Hospital. All of them were initially stratified based
      on the National Cancer Institute (NCI) risk; 48 (46.2%) were diagnosed with high
      risk ALL. The medical charts of these patients were retrospectively reviewed.
      RESULTS: Twenty (19.2%) of the 104 children with ALL had initial leukocyte counts
      of >100*10(9)/L, and 11 patients had a leukocyte count of >200*10(9)/L. Male
      gender, T-cell phenotype, and massive splenomegaly were positively associated
      with hyperleukocytosis. Common early complications during induction therapy
      included renal dysfunction, and central nervous system hemorrhage. The complete
      remission (CR) rate for the pediatric ALL patients with hyperleukocytosis (94.1%)
      was similar to the overall CR rate (95.6%). The estimated 3-year event free
      survival (EFS) and overall survival of ALL children with hyperleukocytosis were
      75.0% and 81.2%, respectively. However, patients with initial leukocyte counts
      >200*10(9)/L had a lower EFS than those with initial leukocyte counts 100
      200*10(9)/L (63.6% vs. 100%; P=0.046). CONCLUSION: The outcome of pediatric ALL
      cases with an initial leukocyte count >200*10(9)/L was very poor, probably due to
      early toxicity-related death during induction therapy.

PMID- 24724065
TI  - Primary mediastinal large B-cell lymphoma: a single-center experience in Korea.
AB  - BACKGROUND: Primary mediastinal large B-cell lymphoma (PMBL) is a distinct
      subtype of non-Hodgkin lymphoma, which has no consensus for its ideal treatment
      or prognosis. METHODS: We reviewed the clinicopathologic features and clinical
      outcomes of 25 PMBL cases diagnosed at a single institution between 1993 and 2009
      and compared them with 588 cases of non-mediastinal, diffuse large B-cell
      lymphoma (DLBCL, control group) diagnosed during the same period. RESULTS:
      Thirteen (52.0%) PMBL patients had Ann Arbor stage III or IV disease, and 10
      (40.0%) had B symptoms. Thirteen (52%) PMBL patients were classified as high
      intermediate/high-risk according to the International Prognostic Index. There was
      a significant prevalence of young (median: 31 years; range, 15-78 years;
      P<0.001), female (68%; P=0.014) patients in the PMBL group compared to the
      control group (median: 56 years; range, 15-85 years; 43.2% female). Bulky disease
      and elevated levels of lactate dehydrogenase (LDH) were more frequent in the PMBL
      group (P<0.001 and P=0.003, respectively). Nineteen (76%) PBML patients achieved
      complete remission, and 18 were alive at the last follow-up (median: 43 months;
      range, 1-92 months). There was no difference in the 3-year, overall survival rate
      (72%, 95% confidence interval [CI]: 54.0-83.0 versus 70.1%, 95% CI, 109.0-126.0;
      P=0.686) between PMBL and control patients, respectively. CONCLUSION: Compared to
      patients with non-mediastinal DLBCL, Korean patients with PMBL are predominantly
      young women with bulky disease and high LDH levels but with no significant
      difference in survival.

PMID- 24724066
TI  - Advanced POEMS syndrome treated with high-dose melphalan followed by autologous
      blood stem cell transplantation: a single-center experience.
AB  - BACKGROUND: POEMS syndrome is a rare paraneoplastic syndrome associated with
      plasma cell dyscrasia. High-dose chemotherapy followed by autologous stem cell
      transplantation has shown encouraging efficacy in the treatment of patients with
      POEMS syndrome. However, there are minimal reports on clinical outcomes after
      autologous stem cell transplantation for patients with advanced disease and very
      poor performance status. METHODS: We retrospectively evaluated 9 advanced POEMS
      syndrome patients, who had an Eastern Cooperative Oncology Group performance
      status score of 3 or 4, and were treated with high-dose melphalan therapy
      followed by autologous stem cell transplantation from 2004 to 2011. RESULTS:
      Eight patients achieved initial hematologic response, 4 of whom had complete
      responses. At a median follow-up of 44 months (range, 8-94 months), 7 patients
      were alive, with 3-year overall survival rate of 77.8%. There were no hematologic
      relapses in the survivors. One patient died of disease progression; the other
      died of pneumonia despite a hematologic response 3 months after autologous stem
      cell transplantation. All survivors achieved improvement in general performance
      status and in clinical response. CONCLUSION: High-dose melphalan followed by
      autologous stem cell transplantation can be considered a valid treatment option
      even for patients with advanced POEMS syndrome.

PMID- 24724067
TI  - The caspase-3 inhibitor (peptide Z-DEVD-FMK) affects the survival and function of
      platelets in platelet concentrate during storage.
AB  - BACKGROUND: Although apoptosis occurs in nucleated cells, studies show that this
      event also occurs in some anucleated cells such as platelets. During storage of
      platelets, the viability of platelets decreased, storage lesions were observed,
      and cells underwent apoptosis. We investigated the effects of caspase-3 inhibitor
      on the survival and function of platelets after different periods of storage.
      METHODS: Platelet concentrates were obtained from the Iranian Blood Transfusion
      Organization in plastic blood bags. Caspase-3 inhibitor (Z-DEVD-FMK) was added to
      the bags. These bags along with control bags to which no inhibitor was added were
      stored in a shaking incubator at 22C for 7 days. The effects of Z-DEVD-FMK on the
      functionality of platelets were analyzed by assessing their ability to bind to
      von Willebrand factor (vWF) and to aggregate in the presence of arachidonic acid
      and ristocetin. Cell survival was surveyed by MTT assay. RESULTS: At day 4 of
      storage, ristocetin-induced platelet aggregation was significantly higher in the
      inhibitor-treated (test) than in control samples; the difference was not
      significant at day 7. There was no significant difference in arachidonic acid
      induced platelet aggregation between test and control samples. However, at day 7
      of storage, the binding of platelets to vWF was significantly higher in test than
      in control samples. The MTT assay revealed significantly higher viability in test
      than in control samples at both days of study. CONCLUSION: Treatment of platelets
      with caspase-3 inhibitor could increase their functionality and survival.

PMID- 24724068
TI  - Quality of cord blood cryopreserved for up to 5 years.
AB  - BACKGROUND: Although cord blood (CB) is a well-known source of hematopoietic stem
      cells, uncertainties exist regarding the quality of cryopreserved CB. We
      investigated the changes in quality of CB units according to the duration of
      cryopreservation. METHODS: We analyzed CB units that were rejected from the Seoul
      Metropolitan Government Public Cord Blood Bank inventory after conventional
      processing, because of unsuitability for allogeneic transplantation. Two hundred
      CB units that were cryopreserved from 1 year to 5 years were selected. After
      thawing the cryopreserved CB units, the total nucleated cell (TNC) count, CD34+
      cell count, number of colony-forming units (CFU), aldehyde dehydrogenase (ALDH)
      level, cell viability, and apoptosis were analyzed. We conducted a comparative
      analysis to identify the presence of statistically significant differences in the
      recovery rates of the TNC and CD34+ cell counts and to compare the results of
      ALDH level, the cell viability test, the apoptosis test, and CFU analysis among
      groups according to the duration of cryopreservation. RESULTS: The recovery rates
      of the TNC count, the CD34+ cell count, and cell viability did not differ
      significantly according to the duration of cryopreservation. ALDH analysis, the
      cell viability test, and the apoptosis test did not reveal any increasing or
      decreasing trend according to the duration of cryopreservation. Further, the
      numbers of CFU-granulocyte/macrophage and CFU
      granulocyte/erythrocyte/macrophage/megakaryocyte did not differ significantly
      according to the duration of cryopreservation. CONCLUSION: These results suggest
      that the quality of CB is not affected by cryopreservation for up to a period of
      5 years.

PMID- 24724069
TI  - A case of oxaliplatin-induced immune-mediated thrombocytopenia.
AB  - Oxaliplatin is a platinum compound used in patients with gastrointestinal
      malignancies. It is known to evoke a drug-induced immune-mediated
      thrombocytopenia, which has not been reported in Korea. We describe a 53-year-old
      man who developed oxaliplatin-induced immune-mediated thrombocytopenia during
      chemotherapy for colon cancer. Oxaliplatin-dependent IgG platelet antibodies were
      detected in his serum on flow cytometry. He was treated with immunoglobulin and
      corticosteroids without any complications. Physicians should consider oxaliplatin
      induced immune-mediated thrombocytopenia, when a sudden, isolated
      thrombocytopenia develops during chemotherapy with oxaliplatin. 

PMID- 24724070
TI  - Acute myeloid leukemia arising from chronic myelomonocytic leukemia during
      hypomethylating therapy.

PMID- 24724071
TI  - A rare case of isolated myeloid sarcoma of the small gut with inv(16)(p13;q22)
      without bone marrow involvement.

PMID- 24724072
TI  - Pure erythroid leukemia in advanced breast cancer.

PMID- 24724073
TI  - Efficacy and safety of combined oral iron chelation therapy with deferasirox and
      deferiprone in a patient with beta-thalassemia major and persistent iron
      overload.

PMID- 24724074
TI  - Non-invasive cardiac output measurement in low and very low birth weight infants:
      a method comparison.
AB  - BACKGROUND: Cardiac output (CO) measurement in low (LBW) and very low (VLBW)
      birth weight infants is difficult. Hitherto, sporadical transthoracic
      echocardiography (TTE) is the only non-invasive measurement method. Electrical
      velocimetry (EV) has been evaluated as an alternative in normal weight newborns.
      OBJECTIVES: The study was designed to evaluate if EV could be interchangeable
      with TTE even in LBW and VLBW infants. METHODS: In 28 (17 LBW, 11 VLBW) pre
      mature newborns, n = 228 simultaneous TTE (trans-aortic Doppler), and EV
      measurements (134 LBW, 94 VLBW) of stroke volume (SV) and heart rate (HR) were
      performed, thereof calculating body weight indexed SV (=SV*) and CO (=CO*) for
      all patients and the subgroups. Method comparison was performed by Bland-Altman
      plot, method precision expressed by calculation of the coefficient of variation
      (CV). RESULTS: Mean CO* in all patients was 256.4 +/- 44.8 (TTE) and 265.3 +/-
      48.8 (EV) ml/kg/min. Bias and precision were clinically acceptable, limits of
      agreement within the 30% criterion for method interchangeability (17). According
      to their different anatomic dimensions and pathophysiology, there were
      significant differences of SV(*), HR, and CO* for LBW and VLBW infants as well
      for inotropic treatment and ventilation mode. CONCLUSION: Extending recent
      publications on EV/TTE comparison in newborns, this study suggests that EV is
      also applicable in LWB/VLBW infants as a safe and easy to handle method for
      continuous CO monitoring in the NICU and PCICU.

PMID- 24724075
TI  - Current Status of Pediatric Labeling in China and the near Future Efforts Needed
      for the Country.
AB  - BACKGROUND: Children are recognized as "therapeutic orphan" in many parts of the
      world, one expression of this is the lack of adequate pediatric labeling
      information. Some research studies have been done to investigate the pediatric
      labeling condition in the U.S. and other countries, but no national studies had
      been carried out in China. This survey was conducted aiming to inquire the
      current situation of pediatric labeling in China. METHODS: We investigated 6020
      child-applied medicines from 15 representative Chinese hospitals, and analyzed
      the information according to the dosage forms, therapeutic category, and label
      information integrity. RESULTS: Among all these medicines, only 238 (3.95%) are
      pediatric products, the rest are adult formulations with an extended use in
      children. The major pediatric formulations were injection (45.95%), tablet
      (23.69%), and capsule (4.93%), respectively. Alimentary tract/metabolism medicine
      (24.70%) and infections medicines (20.60%) had the most species. In prescription
      drugs, only 210 of 5187 (4%) medicines had adequate pediatric labeling
      information. The main cause of this deficiency was lack of evidence derived from
      pediatric clinical trials. CONCLUSION: The dilemma of "therapeutic orphan"
      requires significant attention. Inadequate labeling information and lack of
      pediatric clinical trials were two prominent issues in China. It calls for more
      efforts from pharmaceutical industries, regulatory agencies, and legislature in
      China to collaborate and find solution to improve the situation.

PMID- 24724076
TI  - Adolescent girls' understanding of tetanus infection and prevention: implications
      for the disease control in Western Nigeria.
AB  - Tetanus is a major cause of morbidity and mortality in developing countries.
      Nigeria is aiming to eliminate tetanus by maintaining coverage of routine
      vaccinations for infants and pregnant women, but little attention is given to the
      adolescents' needs. This study assessed the understanding of adolescent girls
      about tetanus infection and prevention in order to provide information that may
      foster better policy. In this cross-sectional analytical study, 851 female
      adolescents were selected from eight secondary schools in Ibadan, south-west of
      Nigeria using a three-stage random sampling technique. A pre-tested structured
      questionnaire was used to obtain information on demographic and socio-economic
      characteristics, history of tetanus vaccination, and adolescents' knowledge of
      tetanus infection. Mean age of respondents was 14.3 +/- 1.9 years. Only 3.1% had
      received tetanus toxoid injection 1 year prior to the study, most frequently
      following a "wound or injury" (65.4%). Though 344 (40.4%) respondents claimed
      that they knew about tetanus as a "serious neurological disease," only 46.5%
      correctly defined tetanus. Overall, the mean knowledge score was 4.8 +/- 3.1 and
      64.7% of the respondents had poor knowledge. Academic class was significantly
      associated with knowledge; higher mean score among the senior (5.3 +/- 5.3) than
      junior classes (4.4 +/- 3.2); p < 0.001. Over half (56.2%) of the adolescents
      disagreed with the statement that "tetanus immunization can be given to students
      in the school premises." There is the need to improve immunization campaigns
      against tetanus among adolescent girls and consider the introduction of school
      based immunization programs if the elimination of maternal and neonatal tetanus
      is to be achieved. 

PMID- 24724077
TI  - Molecular evolution of the vertebrate FK506 binding protein 25.
AB  - FK506 binding proteins (FKBPs) belong to immunophilins with peptidyl-prolyl
      isomerases (PPIases) activity. FKBP25 (also known as FKBP3) is one of the nuclear
      DNA-binding proteins in the FKBPs family, which plays an important role in
      regulating transcription and chromatin structure. The calculation of
      nonsynonymous and synonymous substitution rates suggested that FKBP25 undergoes
      purifying selection throughout the whole vertebrate evolution. Moreover, the
      result of site-specific tests showed that no sites were detected under positive
      selection. Only one PPIase domain was detected by searching FKBP25 sequences at
      Pfam and SMART domain databases. Mammalian FKBP25 possess exon-intron
      conservation, although conservation in the whole vertebrate lineage is
      incomplete. The result of this study suggests that the purifying selection
      triggers FKBP25 evolutionary history, which allows us to discover the complete
      role of the PPIase domain in the interaction between FKBP25 and nuclear proteins.
      Moreover, intron alterations during FKBP25 evolution that regulate gene splicing
      may be involved in the purifying selection. 

PMID- 24724079
TI  - Evidence of Leishmania infantum infection in rabbits (Oryctolagus cuniculus) in a
      natural area in Madrid, Spain.
AB  - Leishmaniasis is one of the most important neglected zoonosis and remains endemic
      in at least 88 developing countries in the world. In addition, anthropogenic
      environmental changes in urban areas are leading to its emergency world wide.
      Zoonotic leishmaniasis control might only be achieved by an integrated approach
      targeting both the human host and the animal reservoirs, which in certain
      sylvatic cycles are yet to be identified. Recently, hares have been pointed out
      as competent reservoirs of Leishmania infantum in Spain, but the role of other
      lagomorphs has not been clarified. Here, 69 rabbits (Oryctolagus cuniculus) from
      a natural area in Madrid in which a high density was present were analyzed using
      indirect (immunofluorescence antibody test, IFAT) and direct (PCR, culture)
      techniques. Fifty-seven (82.6%) of the animals were positive to at least one
      technique, with IFAT yielding the highest proportion of positive samples. L.
      infantum was isolated in 13% animals demonstrating the occurrence of infection in
      this setting. Our results suggest that rabbits could play a role of competent
      reservoir of L. infantum and demonstrate that the prevalence of infection is high
      in the analyzed area. 

PMID- 24724078
TI  - Purification and biochemical characterization of three myotoxins from Bothrops
      mattogrossensis snake venom with toxicity against Leishmania and tumor cells.
AB  - Bothrops mattogrossensis snake is widely distributed throughout eastern South
      America and is responsible for snakebites in this region. This paper reports the
      purification and biochemical characterization of three new phospholipases A2
      (PLA2s), one of which is presumably an enzymatically active Asp49 and two are
      very likely enzymatically inactive Lys49 PLA2 homologues. The purification was
      obtained after two chromatographic steps on ion exchange and reverse phase
      column. The 2D SDS-PAGE analysis revealed that the proteins have pI values around
      10, are each made of a single chain, and have molecular masses near 13 kDa, which
      was confirmed by MALDI-TOF mass spectrometry. The N-terminal similarity analysis
      of the sequences showed that the proteins are highly homologous with other Lys49
      and Asp49 PLA2s from Bothrops species. The PLA2s isolated were named BmatTX-I
      (Lys49 PLA2-like), BmatTX-II (Lys49 PLA2-like), and BmatTX-III (Asp49 PLA2). The
      PLA2s induced cytokine release from mouse neutrophils and showed cytotoxicity
      towards JURKAT (leukemia T) and SK-BR-3 (breast adenocarcinoma) cell lines and
      promastigote forms of Leishmania amazonensis. The structural and functional
      elucidation of snake venoms components may contribute to a better understanding
      of the mechanism of action of these proteins during envenomation and their
      potential pharmacological and therapeutic applications. 

PMID- 24724080
TI  - Nanosized mesoporous bioactive glass/poly(lactic-co-glycolic acid) composite
      coated CaSiO3 scaffolds with multifunctional properties for bone tissue
      engineering.
AB  - It is of great importance to prepare multifunctional scaffolds combining good
      mechanical strength, bioactivity, and drug delivery ability for bone tissue
      engineering. In this study, nanosized mesoporous bioglass/poly(lactic-co-glycolic
      acid) composite-coated calcium silicate scaffolds, named NMBG-PLGA/CS, were
      successfully prepared. The morphology and structure of the prepared scaffolds
      were characterized by scanning electron microscopy and X-ray diffraction. The
      effects of NMBG on the apatite mineralization activity and mechanical strength of
      the scaffolds and the attachment, proliferation, and alkaline phosphatase
      activity of MC3T3 cells as well as drug ibuprofen delivery properties were
      systematically studied. Compared to pure CS scaffolds and PLGA/CS scaffolds, the
      prepared NMBG-PLGA/CS scaffolds had greatly improved apatite mineralization
      activity in simulated body fluids, much higher mechanical property, and supported
      the attachment of MC3T3 cells and enhanced the cell proliferation and ALP
      activity. Furthermore, the prepared NMBG-PLGA/CS scaffolds could be used for
      delivering ibuprofen with a sustained release profile. Our study suggests that
      the prepared NMBG-PLGA/CS scaffolds have improved physicochemical, biological,
      and drug-delivery property as compared to conventional CS scaffolds, indicating
      that the multifunctional property of the prepared scaffolds for the potential
      application of bone tissue engineering. 

PMID- 24724081
TI  - Oxygenation, ventilation, and airway management in out-of-hospital cardiac
      arrest: a review.
AB  - Recently published evidence has challenged some protocols related to oxygenation,
      ventilation, and airway management for out-of-hospital cardiac arrest.
      Interrupting chest compressions to attempt airway intervention in the early
      stages of OHCA in adults may worsen patient outcomes. The change of BLS
      algorithms from ABC to CAB was recommended by the AHA in 2010. Passive
      insufflation of oxygen into a patent airway may provide oxygenation in the early
      stages of cardiac arrest. Various alternatives to tracheal intubation or bag-mask
      ventilation have been trialled for prehospital airway management. Simple methods
      of airway management are associated with similar outcomes as tracheal intubation
      in patients with OHCA. The insertion of a laryngeal mask airway is probably
      associated with worse neurologically intact survival rates in comparison with
      other methods of airway management. Hyperoxemia following OHCA may have a
      deleterious effect on the neurological recovery of patients. Extracorporeal
      oxygenation techniques have been utilized by specialized centers, though their
      use in OHCA remains controversial. Chest hyperinflation and positive airway
      pressure may have a negative impact on hemodynamics during resuscitation and
      should be avoided. Dyscarbia in the postresuscitation period is relatively
      common, mainly in association with therapeutic hypothermia, and may worsen
      neurological outcome. 

PMID- 24724082
TI  - Involvement of oxidative stress and inflammation in liver injury caused by
      perfluorooctanoic acid exposure in mice.
AB  - Perfluorooctanoic acid (PFOA) is widely present in the environment and has been
      reported to induce hepatic toxicity in animals and humans. In this study, mice
      were orally administered different concentrations of PFOA (2.5, 5, or 10
      mg/kg/day). Histological examination showed that the exposure to PFOA for 14
      consecutive days led to serious hepatocellular injury and obvious inflammatory
      cell infiltration. In addition, malondialdehyde formation and hydrogen peroxide
      generation, indicators of oxidative stress, were significantly induced by PFOA
      treatment in the liver of mice. Furthermore, hepatic levels of interleukin-6,
      cyclooxygenase-2, and C-reactive protein, markers of inflammatory response, were
      markedly increased by exposure to PFOA in mice. These results demonstrated that
      PFOA-induced hepatic toxicity may be involved in oxidative stress and
      inflammatory response in mice. 

PMID- 24724083
TI  - Folic acid supplementation and preterm birth: results from observational studies.
AB  - INTRODUCTION: Folic acid (FA) supplementation is recommended worldwide in the
      periconceptional period for the prevention of neural tube defects. Due to its
      involvement in a number of cellular processes, its role in other pregnancy
      outcomes such as miscarriage, recurrent miscarriage, low birth weight, preterm
      birth (PTB), preeclampsia, abruptio placentae, and stillbirth has been
      investigated. PTB is a leading cause of perinatal mortality and morbidity;
      therefore its association with FA supplementation is of major interest. The
      analysis of a small number of randomized clinical trials (RCTs) has not found a
      beneficial role of FA in reducing the rate of PTBs. AIM OF THE STUDY: The aim of
      this review was to examine the results from recent observational studies about
      the effect of FA supplementation on PTB. MATERIALS AND METHODS: We carried out a
      search on Medline and by manual search of the observational studies from 2009
      onwards that analyzed the rate of PTB in patients who received supplementation
      with FA before and/or throughout pregnancy. RESULTS: The results from recent
      observational studies suggest a slight reduction of PTBs that is not consistent
      with the results from RCTs. Further research is needed to better understand the
      role of FA supplementation before and during pregnancy in PTB.

PMID- 24724084
TI  - Expression of mesenchymal stem cells-related genes and plasticity of aspirated
      follicular cells obtained from infertile women.
AB  - After removal of oocytes for in vitro fertilization, follicular aspirates which
      are rich in somatic follicular cells are discarded in daily medical practice.
      However, there is some evidence that less differentiated cells with stem cell
      characteristics are present among aspirated follicular cells (AFCs). The aim of
      this study was to culture AFCs in vitro and to analyze their gene expression
      profile. Using the RT2 Profiler PCR array, we investigated the expression profile
      of 84 genes related to stemness, mesenchymal stem cells (MCSs), and cell
      differentiation in AFCs enriched by hypoosmotic protocol from follicular
      aspirates of infertile women involved in assisted reproduction programme in
      comparison with bone marrow-derived mesenchymal stem cells (BM-MSCs) and
      fibroblasts. Altogether the expression of 57 genes was detected in AFCs: 16 genes
      (OCT4, CD49f, CD106, CD146, CD45, CD54, IL10, IL1B, TNF, VEGF, VWF, HDAC1, MITF,
      RUNX2, PPARG, and PCAF) were upregulated and 20 genes (FGF2, CASP3, CD105, CD13,
      CD340, CD73, CD90, KDR, PDGFRB, BDNF, COL1A1, IL6, MMP2, NES, NUDT6, BMP6,
      SMURF2, BMP4, GDF5, and JAG1) were downregulated in AFCs when compared with BM
      MSCs. The genes which were upregulated in AFCs were mostly related to MSCs and
      connected with ovarian function, and differed from those in fibroblasts. The
      cultured AFCs with predominating granulosa cells were successfully in vitro
      differentiated into adipogenic-, osteogenic-, and pancreatic-like cells. The
      upregulation of some MSC-specific genes and in vitro differentiation into other
      types of cells indicated a subpopulation of AFCs with specific stemness, which
      was not similar to those of BM-MSCs or fibroblasts.

PMID- 24724086
TI  - Detection of carbapenemase-producing enterobacteriaceae in the baltic countries
      and st. Petersburg area.
AB  - The spread of carbapenemase-producing Enterobacteriaceae is a global problem;
      however, no exact data on the epidemiology of carbapenemase in the Baltic
      countries and St. Petersburg area is available. We aimed to evaluate the
      epidemiology of carbapenemase-producing Escherichia coli and Klebsiella
      pneumoniae in the Baltic States and St. Petersburg, Russia, and to compare the
      different methods for carbapenemase detection. From January to May 2012, all K.
      pneumoniae (n = 1983) and E. coli (n = 7774) clinical isolates from 20
      institutions in Estonia, Latvia, Lithuania, and St. Petersburg, Russia were
      screened for carbapenem susceptibility. The IMP, VIM, GIM, NDM, KPC, and OXA-48
      genes were detected using real-time PCR and the ability to hydrolyze ertapenem
      was determined using MALDI-TOF MS. Seventy-seven strains were found to be
      carbapenem nonsusceptible. From these, 15 K. pneumoniae strains hydrolyzed
      ertapenem and carried the bla NDM gene. All of these strains carried integron 1
      and most carried integron 3 as well as genes of the CTX-M-1 group. No
      carbapenemase-producing E. coli or K. pneumoniae strains were found in Estonia,
      Latvia, or Lithuania; however, NDM-positive K. pneumoniae was present in the
      hospital in St. Petersburg, Russia. A MALDI-TOF MS-based assay is a suitable and
      cost-effective method for the initial confirmation of carbapenemase production. 

PMID- 24724085
TI  - Acute exacerbation of chronic obstructive pulmonary disease: cardiovascular
      links.
AB  - Chronic obstructive pulmonary disease (COPD) is a chronic, progressive lung
      disease resulting from exposure to cigarette smoke, noxious gases, particulate
      matter, and air pollutants. COPD is exacerbated by acute inflammatory insults
      such as lung infections (viral and bacterial) and air pollutants which further
      accelerate the steady decline in lung function. The chronic inflammatory process
      in the lung contributes to the extrapulmonary manifestations of COPD which are
      predominantly cardiovascular in nature. Here we review the significant burden of
      cardiovascular disease in COPD and discuss the clinical and pathological links
      between acute exacerbations of COPD and cardiovascular disease. 

PMID- 24724087
TI  - Development of a promising fish model (Oryzias melastigma) for assessing multiple
      responses to stresses in the marine environment.
AB  - With the increasing number of contaminants in the marine environment, various
      experimental organisms have been "taken into labs" by investigators to find the
      most suitable environmentally relevant models for toxicity testing. The marine
      medaka, Oryzias melastigma, has a number of advantages that make it a prime
      candidate for these tests. Recently, many studies have been conducted on marine
      medaka, especially in terms of their physiological, biochemical, and molecular
      responses after exposure to contaminants and other environmental stressors. This
      review provides a literature survey highlighting the steady increase of
      ecotoxicological research on marine medaka, summarizes the advantages of using O.
      melastigma as a tool for toxicological research, and promotes the utilization of
      this organism in future studies. 

PMID- 24724088
TI  - Brachial artery endothelial responses during early recovery from an exercise bout
      in patients with coronary artery disease.
AB  - This study examined the acute endothelial responses to an exercise bout in
      coronary artery disease (CAD) patients. Nineteen males with CAD (63 +/- 8 years)
      were assessed at rest and 15 minutes following a submaximal exercise bout
      (recovery). Brachial artery endothelial-dependent function was assessed using
      flow-mediated dilation (FMD). Brachial artery diameters and velocities were
      measured using Duplex ultrasound at baseline, and for 3 minutes following a 5
      minute ischemic period. Endothelial-independent function was assessed using a 0.4
      mg dose of nitroglycerin (NTG). FMD responses were unchanged from rest to
      recovery; however, there were 2 types of responses: negative and positive FMD
      responders. Post-hoc analysis revealed that positive responders had lower resting
      FMD compared to negative responders (3.2 +/- 1.7 versus 6.0 +/- 2.5%, P < 0.05).
      NTG-mediated dilation was reduced in recovery (22.0 +/- 5.6 versus 14.4 +/- 5.7%,
      P < 0.001 for rest versus recovery). In conclusion, acute endothelial-dependent
      responses to submaximal exercise are affected by the degree of resting
      endothelial dysfunction. The observation of attenuated NTG-mediated dilation
      during recovery is novel and warrants the investigation of possible mechanisms
      and clinical significance. Furthermore, it highlights the necessity of both
      endothelial-dependent and endothelial-independent assessments when evaluating
      endothelial function changes with an intervention. 

PMID- 24724089
TI  - High-intensity interval training in patients with substance use disorder.
AB  - Patients with substance use disorder (SUD) suffer a higher risk of cardiovascular
      disease and other lifestyle diseases compared to the general population. High
      intensity training has been shown to effectively reduce this risk, and therefore
      we aimed to examine the feasibility and effect of such training in SUD patients
      in clinical treatment in the present study. 17 males and 7 females (32 +/- 8 yr)
      in treatment were randomized to either a training group (TG), treadmill interval
      training in 4 * 4 minutes at 90-95% of maximal heart rate, 3 days a week for 8
      weeks, or a conventional rehabilitation control group (CG). Baseline values for
      both groups combined at inclusion were 44 +/- 8 (males) and 34 +/- 9 (females) mL
      . min(-1) . kg(-1), respectively. 9/12 and 7/12 patients completed the TG and CG,
      respectively. Only the TG significantly improved (15 +/- 7%) their maximal oxygen
      consumption (VO2max), from 42.3 +/- 7.2 mL . min(-1) . kg(-1) at pretest to 48.7
      +/- 9.2 mL . min(-1) . kg(-1) at posttest. No between-group differences were
      observed in work economy, and level of insomnia (ISI) or anxiety and depression
      (HAD), but a significant within-group improvement in depression was apparent for
      the TG. High intensity training was feasible for SUD patients in treatment. This
      training form should be implemented as a part of the rehabilitation since it, in
      contrast to the conventional treatment, represents a risk reduction for
      cardiovascular disease and premature death. 

PMID- 24724091
TI  - Chitooligosaccharide and its derivatives: preparation and biological
      applications.
AB  - Chitin is a natural polysaccharide of major importance. This biopolymer is
      synthesized by an enormous number of living organisms; considering the amount of
      chitin produced annually in the world, it is the most abundant polymer after
      cellulose. The most important derivative of chitin is chitosan, obtained by
      partial deacetylation of chitin under alkaline conditions or by enzymatic
      hydrolysis. Chitin and chitosan are known to have important functional activities
      but poor solubility makes them difficult to use in food and biomedicinal
      applications. Chitooligosaccharides (COS) are the degraded products of chitosan
      or chitin prepared by enzymatic or chemical hydrolysis of chitosan. The greater
      solubility and low viscosity of COS have attracted the interest of many
      researchers to utilize COS and their derivatives for various biomedical
      applications. In light of the recent interest in the biomedical applications of
      chitin, chitosan, and their derivatives, this review focuses on the preparation
      and biological activities of chitin, chitosan, COS, and their derivatives. 

PMID- 24724090
TI  - Current opportunities and challenges of magnetic resonance spectroscopy, positron
      emission tomography, and mass spectrometry imaging for mapping cancer metabolism
      in vivo.
AB  - Cancer is known to have unique metabolic features such as Warburg effect. Current
      cancer therapy has moved forward from cytotoxic treatment to personalized,
      targeted therapies, with some that could lead to specific metabolic changes,
      potentially monitored by imaging methods. In this paper we addressed the
      important aspects to study cancer metabolism by using image techniques, focusing
      on opportunities and challenges of magnetic resonance spectroscopy (MRS), dynamic
      nuclear polarization (DNP)-MRS, positron emission tomography (PET), and mass
      spectrometry imaging (MSI) for mapping cancer metabolism. Finally, we highlighted
      the future possibilities of an integrated in vivo PET/MR imaging systems,
      together with an in situ MSI tissue analytical platform, may become the ultimate
      technologies for unraveling and understanding the molecular complexities in some
      aspects of cancer metabolism. Such comprehensive imaging investigations might
      provide information on pharmacometabolomics, biomarker discovery, and disease
      diagnosis, prognosis, and treatment response monitoring for clinical medicine. 

PMID- 24724092
TI  - Efficacy of three light technologies for reducing microbial populations in liquid
      suspensions.
AB  - The aim of the current study was to evaluate the effectiveness of three
      nonthermal light technologies (NUV-Vis, continuous UV, and HILP) on their ability
      to inactivate Escherichia coli K12 and Listeria innocua.  E. coli K12 was
      selected as a representative microorganism for the enterohaemorrhagic foodborne
      pathogen E. coli O157:H7 and L. innocua as a surrogate microorganism for the
      common foodborne pathogen Listeria monocytogenes, respectively. The liquid matrix
      used for the disinfection experiments was a liquid matrix (MRD solution). The
      results of the present study show that the HILP treatment inactivated both E.
      coli and L. innocua more rapidly and effectively than either continuous UV-C or
      NUV-vis treatment. With HILP at 2.5 cm from the lamp, E. coli and L. innocua
      populations were reduced by 3.07 and 3.77 log10 CFU/mL, respectively, after a 5
      sec treatment time, and were shown to be below the limit of detection (<0.22
      log10 CFU/mL) following 30 sec exposure to HILP (106.2 J/cm(2)). These studies
      demonstrate the bactericidal efficacy of alternative nonthermal light
      technologies and their potential as decontamination strategies in the food
      industry. 

PMID- 24724093
TI  - Reduced amygdala volume is associated with deficits in inhibitory control: a
      voxel- and surface-based morphometric analysis of comorbid PTSD/mild TBI.
AB  - A significant portion of previously deployed combat Veterans from Operation
      Enduring Freedom and Operation Iraqi Freedom/Operation New Dawn (OEF/OIF/OND) are
      affected by comorbid posttraumatic stress disorder (PTSD) and mild traumatic
      brain injury (mTBI). Despite this fact, neuroimaging studies investigating the
      neural correlates of cognitive dysfunction within this population are almost
      nonexistent, with the exception of research examining the neural correlates of
      diagnostic PTSD or TBI. The current study used both voxel-based and surface-based
      morphometry to determine whether comorbid PTSD/mTBI is characterized by altered
      brain structure in the same regions as observed in singular diagnostic PTSD or
      TBI. Furthermore, we assessed whether alterations in brain structures in these
      regions were associated with behavioral measures related to inhibitory control,
      as assessed by the Go/No-go task, self-reports of impulsivity, and/or PTSD or
      mTBI symptoms. Results indicate volumetric reductions in the bilateral anterior
      amygdala in our comorbid PTSD/mTBI sample as compared to a control sample of
      OEF/OIF Veterans with no history of mTBI and/or PTSD. Moreover, increased volume
      reduction in the amygdala predicted poorer inhibitory control as measured by
      performance on the Go/No-go task, increased self-reported impulsivity, and
      greater symptoms associated with PTSD. These findings suggest that alterations in
      brain anatomy in OEF/OIF/OND Veterans with comorbid PTSD/mTBI are associated with
      both cognitive deficits and trauma symptoms related to PTSD. 

PMID- 24724094
TI  - Role of the vasa vasorum and vascular resident stem cells in atherosclerosis.
AB  - Atherosclerosis is considered an "inside-out" response, that begins with the
      dysfunction of intimal endothelial cells and leads to neointimal plaque
      formation. The adventitia of large blood vessels has been recognized as an active
      part of the vessel wall that is involved in the process of atherosclerosis. There
      are characteristic changes in the adventitial vasa vasorum that are associated
      with the development of atheromatous plaques. However, whether vasa vasorum plays
      a causative or merely reactive role in the atherosclerotic process is not
      completely clear. Recent studies report that the vascular wall contains a number
      of stem/progenitor cells that may contribute to vascular remodeling. Microvessels
      serve as the vascular niche that maintains the resident stem/progenitor cells of
      the tissue. Therefore, the vasa vasorum may contribute to vascular remodeling
      through not only its conventional function as a blood conducting tube, but also
      its new conceptual function as a stem cell reservoir. This brief review
      highlights the recent advances contributing to our understanding of the role of
      the adventitial vasa vasorum in the atherosclerosis and discusses new concept
      that involves vascular-resident factors, the vasa vasorum and its associated
      vascular-resident stem cells, in the atherosclerotic process. 

PMID- 24724095
TI  - Therapeutic implications of estrogen for cerebral vasospasm and delayed cerebral
      ischemia induced by aneurysmal subarachnoid hemorrhage.
AB  - Cerebral vasospasm (CV) remains the leading cause of delayed morbidity and
      mortality following aneurysmal subarachnoid hemorrhage (SAH). However, increasing
      evidence supports etiologies of delayed cerebral ischemia (DCI) other than CV.
      Estrogen, specifically 17 beta -estradiol (E2), has potential therapeutic
      implications for ameliorating the delayed neurological deterioration which
      follows aneurysmal SAH. We review the causes of CV and DCI and examine the
      evidence for E2-mediated vasodilation and neuroprotection. E2 potentiates
      vasodilation by activating endothelial nitric oxide synthase (eNOS), preventing
      increased inducible NOS (iNOS) activity caused by SAH, and decreasing endothelin
      1 production. E2 provides neuroprotection by increasing thioredoxin expression,
      decreasing c-Jun N-terminal kinase activity, increasing neuroglobin levels,
      preventing SAH-induced suppression of the Akt signaling pathway, and upregulating
      the expression of adenosine A2a receptor. The net effect of E2 modulation of
      these various effectors is the promotion of neuronal survival, inhibition of
      apoptosis, and decreased oxidative damage and inflammation. E2 is a potentially
      potent therapeutic tool for improving outcomes related to post-SAH CV and DCI.
      However, clinical evidence supporting its benefits remains lacking. Given the
      promising preclinical data available, further studies utilizing E2 for the
      treatment of patients with ruptured intracranial aneurysms appear warranted. 

PMID- 24724096
TI  - Reexpression of Let-7g microRNA inhibits the proliferation and migration via K
      Ras/HMGA2/snail axis in hepatocellular carcinoma.
AB  - Let-7 family microRNAs have been reported to be downregulated in human
      hepatocellular carcinoma in comparison with normal hepatic tissues. Among them,
      let-7g was identified as the lowest expression using real-time RT-PCR. However,
      the mechanism by which let-7g works in hepatocellular carcinoma remains unknown.
      Here, in our present study, we have had let-7g reexpressed in vitro in
      hepatocellular carcinoma cell lines MHCC97-H and HCCLM3 via transfection. The
      proliferation after reexpression of let-7g was assayed using MTT method; the
      migration and invasion after restoration were detected by wound-healing and
      Transwell assay, respectively. We found using Western-blotting that let-7g can
      regulate epithelial-mesenchymal transition (EMT) by downregulating K-Ras and
      HMGA2A after reexpresssion. Xenografted nude mice were used to observe whether or
      not reexpression of let-7g could have potential therapeutic ability. In vivo, to
      observe the association with let-7g expression and overall prognosis, 40 paired
      cases of hepatocellular carcinoma were analyzed using in situ hybridization
      (ISH). It was found that reexpression of let-7g can inhibit the proliferation,
      migration, and invasion significantly, and that low expression of let-7g was
      significantly associated with poorer overall survival. Taken together, let-7g
      could be used as a promising therapeutic agent in vivo in the treatment of
      hepatocellular carcinoma at the earlier stage. 

PMID- 24724097
TI  - Designs and techniques that improve the pullout strength of pedicle screws in
      osteoporotic vertebrae: current status.
AB  - Osteoporosis is a medical condition affecting men and women of different age
      groups and populations. The compromised bone quality caused by this disease
      represents an important challenge when a surgical procedure (e.g., spinal fusion)
      is needed after failure of conservative treatments. Different pedicle screw
      designs and instrumentation techniques have been explored to enhance spinal
      device fixation in bone of compromised quality. These include alterations of
      screw thread design, optimization of pilot hole size for non-self-tapping screws,
      modification of the implant's trajectory, and bone cement augmentation. While the
      true benefits and limitations of any procedure may not be realized until they are
      observed in a clinical setting, axial pullout tests, due in large part to their
      reproducibility and ease of execution, are commonly used to estimate the device's
      effectiveness by quantifying the change in force required to remove the screw
      from the body. The objective of this investigation is to provide an overview of
      the different pedicle screw designs and the associated surgical techniques either
      currently utilized or proposed to improve pullout strength in osteoporotic
      patients. Mechanical comparisons as well as potential advantages and
      disadvantages of each consideration are provided herein. 

PMID- 24724098
TI  - Data analysis and tissue type assignment for glioblastoma multiforme.
AB  - Glioblastoma multiforme (GBM) is characterized by high infiltration. The
      interpretation of MRSI data, especially for GBMs, is still challenging.
      Unsupervised methods based on NMF by Li et al. (2013, NMR in Biomedicine) and Li
      et al. (2013, IEEE Transactions on Biomedical Engineering) have been proposed for
      glioma recognition, but the tissue types is still not well interpreted. As an
      extension of the previous work, a tissue type assignment method is proposed for
      GBMs based on the analysis of MRSI data and tissue distribution information. The
      tissue type assignment method uses the values from the distribution maps of all
      three tissue types to interpret all the information in one new map and color
      encodes each voxel to indicate the tissue type. Experiments carried out on in
      vivo MRSI data show the feasibility of the proposed method. This method provides
      an efficient way for GBM tissue type assignment and helps to display information
      of MRSI data in a way that is easy to interpret. 

PMID- 24724100
TI  - Characterization of multiwalled carbon nanotube-reinforced hydroxyapatite
      composites consolidated by spark plasma sintering.
AB  - Pure HA and 1, 3, 5, and 10 vol% multiwalled carbon nanotube- (MWNT-) reinforced
      hydroxyapatite (HA) were consolidated using a spark plasma sintering (SPS)
      technique. The relative density of pure HA increased with increasing sintering
      temperature, but that of the MWNT/HA composite reached almost full density at 900
      degrees C, and then decreased with further increases in sintering temperature.
      The relative density of the MWNT/HA composites increased with increasing MWNT
      content due to the excellent thermal conductivity of MWNTs. The grain size of
      MWNT/HA composites decreased with increasing MWNT content and increased with
      increasing sintering temperature. Pull-out toughening of the MWNTs of the MWNT/HA
      composites was observed in the fractured surface, which can be used to predict
      the improvement of the mechanical properties. On the other hand, the existence of
      undispersed or agglomerate MWNTs in the MWNT/HA composites accompanied large
      pores. The formation of large pores increased with increasing sintering
      temperature and MWNT content. The addition of MWNT in HA increased the hardness
      and fracture toughness by approximately 3~4 times, despite the presence of large
      pores produced by un-dispersed MWNTs. This provides strong evidence as to why the
      MWNTs are good candidates as reinforcements for strengthening the ceramic matrix.
      The MWNT/HA composites did not decompose during SPS sintering. The MWNT
      reinforced HA composites were non-toxic and showed a good cell affinity and
      morphology in vitro for 1 day. 

PMID- 24724099
TI  - Suitability of IS6110-RFLP and MIRU-VNTR for differentiating spoligotyped drug
      resistant mycobacterium tuberculosis clinical isolates from Sichuan in China.
AB  - Genotypes of Mycobacterium tuberculosis complex (MTBC) vary with the geographic
      origin of the patients and can affect tuberculosis (TB) transmission. This study
      was aimed to further differentiate spoligotype-defined clusters of drug-resistant
      MTBC clinical isolates split in Beijing (n = 190) versus non-Beijing isolates (n
      = 84) from Sichuan region, the second high-burden province in China, by IS6110
      restriction fragment length polymorphism (RFLP) and 24-locus MIRU-VNTRs. Among
      274 spoligotyped isolates, the clustering ratio of Beijing family was 5.3% by 24
      locus MIRU-VNTRs versus 2.1% by IS6110-RFLP, while none of the non-Beijing
      isolates were clustered by 24-locus MIRU-VNTRs versus 9.5% by IS6110-RFLP. Hence,
      neither the 24-locus MIRU-VNTR was sufficient enough to fully discriminate the
      Beijing family, nor the IS6110-RFLP for the non-Beijing isolates. A region
      adjusted scheme combining 12 highly discriminatory VNTR loci with IS6110-RFLP was
      a better alternative for typing Beijing strains in Sichuan than 24-locus MIRU
      VNTRs alone. IS6110-RFLP was for the first time introduced to systematically
      genotype MTBC in Sichuan and we conclude that the region-adjusted scheme of 12
      highly discriminative VNTRs might be a suitable alternative to 24-locus MIRU-VNTR
      scheme for non-Beijing strains, while the clusters of the Beijing isolates should
      be further subtyped using IS6110-RFLP for optimal discrimination. 

PMID- 24724101
TI  - Evidence for the existence of triple-negative variants in the MCF-7 breast cancer
      cell population.
AB  - The MCF-7 line, derived in 1973 from a malignant pleural effusion, is one of the
      most commonly used culture models for human breast cancer. Despite its long
      history, MCF-7 is a surprisingly heterogeneous line. We previously showed that if
      MCF-7 cells were cultured for a prolonged period either in the absence of
      estrogen or in the presence of the antiestrogen tamoxifen, sub-lines were
      selected that differed from the parental line in ploidy, mean cell volume,
      signaling pathway usage, and drug sensitivity. This suggests a process of
      selection of preexisting variants rather than of adaptation of the parental line.
      All the sublines were estrogen receptor (ER) positive, raising the question of
      whether MCF-7 also contains ER negative variants. Here, we have looked for such
      variants by culturing for a prolonged period in the presence of fulvestrant, an
      estrogen antagonist that has no estrogen agonist activity. Three sublines were
      developed, each of which was ER negative, progesterone receptor (PR) negative and
      expressed only a low level of HER2. Each of the variants differed from the
      original MCF-7 line in ploidy, modal cell volume, and signaling pathway usage.
      Control experiments in which cells were cultured for a prolonged period in the
      absence of estrogen selected for variants that were ER and PR positive. The
      properties of the triple-negative MCF-7 were compared with those of an existing
      triple-negative cell line, MDA-MB-231, and human epidermal growth factor receptor
      2 (HER2)+ SKBr3, as well as from those of the "immortalized" breast epithelial
      line MCF10A. The results suggest that new variants or phenotypes of MCF-7 might
      be generated continuously in culture, and by implication this might apply to
      breast cancer development and even normal breast epithelial development in vivo. 

PMID- 24724102
TI  - Dissolution of arsenic minerals mediated by dissimilatory arsenate reducing
      bacteria: estimation of the physiological potential for arsenic mobilization.
AB  - The aim of this study was characterization of the isolated dissimilatory arsenate
      reducing bacteria in the context of their potential for arsenic removal from
      primary arsenic minerals through reductive dissolution. Four strains, Shewanella
      sp. OM1, Pseudomonas sp. OM2, Aeromonas sp. OM4, and Serratia sp. OM17, capable
      of anaerobic growth with As (V) reduction, were isolated from microbial mats from
      an ancient gold mine. All of the isolated strains: (i) produced siderophores that
      promote dissolution of minerals, (ii) were resistant to dissolved arsenic
      compounds, (iii) were able to use the dissolved arsenates as the terminal
      electron acceptor, and (iii) were able to use copper minerals containing arsenic
      minerals (e.g., enargite) as a respiratory substrate. Based on the results
      obtained in this study, we postulate that arsenic can be released from some As
      bearing polymetallic minerals (such as copper ore concentrates or middlings)
      under reductive conditions by dissimilatory arsenate reducers in indirect
      processes. 

PMID- 24724103
TI  - A novel pedicle screw with mobile connection: a pilot study.
AB  - To prevent adjacent disc problems after spinal fusion, a pedicle screw with a
      mobile junction between the head and threaded shaft was newly developed. The
      threaded shaft of the screw has 10 degrees mobility in all directions, but its
      structure is to prevent abnormal translation and tilting. This screw was
      evaluated as follows: (1) endurance test: 10(6) times rotational stress was
      applied; (2) biological reactions: novel screws with a mobile head and
      conventional screws with a fixed head were inserted into the bilateral pedicles
      of the L3, L4, and L5 in two mini pigs with combination. Eight months after
      surgery, vertebral units with the screw rod constructs were collected. After CT
      scan, the soft and bony tissues around the screws were examined grossly and
      histologically. As a result, none of the screws broke during the endurance test
      stressing. The mean amount of abrasion wear was 0.0338 g. In the resected mini
      pig section, though zygapophyseal joints between fixed-head screws showed bony
      union, the amount of callus in the zygapophyseal joints connected with mobile
      head screws was small, and joint space was confirmed by CT. No metalloses were
      noted around any of the screws. Novel screws were suggested to be highly durable
      and histologically safe. 

PMID- 24724104
TI  - Molybdenum reduction to molybdenum blue in Serratia sp. Strain DRY5 is catalyzed
      by a novel molybdenum-reducing enzyme.
AB  - The first purification of the Mo-reducing enzyme from Serratia sp. strain DRY5
      that is responsible for molybdenum reduction to molybdenum blue in the bacterium
      is reported. The monomeric enzyme has an apparent molecular weight of 105
      kDalton. The isoelectric point of this enzyme was 7.55. The enzyme has an optimum
      pH of 6.0 and maximum activity between 25 and 35 degrees C. The Mo-reducing
      enzyme was extremely sensitive to temperatures above 50 degrees C (between 54 and
      70 degrees C). A plot of initial rates against substrate concentrations at 15 mM
      12-MP registered a V max for NADH at 12.0 nmole Mo blue/min/mg protein. The
      apparent K m for NADH was 0.79 mM. At 5 mM NADH, the apparent V max and apparent
      K m values for 12-MP of 12.05 nmole/min/mg protein and 3.87 mM, respectively,
      were obtained. The catalytic efficiency (k cat/K m ) of the Mo-reducing enzyme
      was 5.47 M(-1) s(-1). The purification of this enzyme could probably help to
      solve the phenomenon of molybdenum reduction to molybdenum blue first reported in
      1896 and would be useful for the understanding of the underlying mechanism in
      molybdenum bioremediation involving bioreduction. 

PMID- 24724105
TI  - Diffusion tensor imaging studies on chinese patients with social anxiety
      disorder.
AB  - The aim of this study was to explore white-matter disruption in social anxiety
      disorder (SAD) patients by using diffusion tensor imaging (DTI) and to
      investigate the relationship between cerebral abnormalities and the severity of
      the symptoms. Eighteen SAD patients and age- and gender-matched healthy controls
      were recruited. DTI scans were performed to measure fractional anisotropy (FA)
      and apparent diffusion coefficient (ADC) for each subject. We used voxel-based
      analysis to determine the differences of FA and ADC values between the two groups
      with two-sample t-tests. The SAD patient showed significantly decreased FA values
      in the white matter of the left insula, left inferior frontal gyrus, left middle
      temporal gyrus, and left inferior parietal gyrus and increased ADC values in the
      left insula, bilateral inferior frontal gyrus, bilateral middle temporal gyrus,
      and left inferior parietal gyrus. In SAD patients, we observed a significant
      negative correlation between FA values in the left insula and the total LSAS
      scores and a positive correlation between the ADC values in the left inferior
      frontal gyrus and the total LSAS scores. Above results suggested that white
      matter microstructural changes might contribute to the neuropathology of SAD. 

PMID- 24724107
TI  - Diabetes and quality of life: a Ugandan perspective.
AB  - Quality of life of diabetic patients is not a new concept in literature. The
      contentious issue however is whether factors associated in literature with
      quality of life apply to diabetic patients in Uganda. A sample of 219 outpatients
      attending Mulago diabetic clinic--a national referral hospital in Uganda--is used
      to provide an understanding of this issue. Quality of life is assessed in the
      dimensions of role limitation due to physical health, emotional health, treatment
      satisfaction, physical endurance, and diet satisfaction based on a five-point
      Likert scale. The analysis is made by patients' characteristics, medical
      conditions, lifestyle factors, and type of medication using frequency
      distributions, summary statistics, and a Poisson regression. In the results, we
      confirm a consensus regarding the influence of age and education level on the
      quality of life in the dimensions of role limitation and physical endurance (P <
      0.05). A similar conclusion is reached with regards to impact of diabetic foot
      ulcers in the dimension of physical endurance. Thus, the factors associated with
      quality of life are not entirely unique to diabetic patients in the country.

PMID- 24724106
TI  - Controversial issues in kyphoplasty and vertebroplasty in osteoporotic vertebral
      fractures.
AB  - Kyphoplasty (KP) and vertebroplasty (VP) have been successfully employed for many
      years for the treatment of osteoporotic vertebral fractures. The purpose of this
      review is to resolve the controversial issues raised by the two randomized trials
      that claimed no difference between VP and SHAM procedure. In particular we
      compare nonsurgical management (NSM) and KP and VP, in terms of clinical
      parameters (pain, disability, quality of life, and new fractures), cost
      effectiveness, radiological variables (kyphosis correction and vertebral height
      restoration), and VP versus KP for cement extravasation and complications
      profile. Cement types and optimal filling are analyzed and technological
      innovations are presented. Finally unipedicular/bipedicular techniques are
      compared. Conclusion. VP and KP are superior to NSM in clinical and radiological
      parameters and probably more cost-effective. KP is superior to VP in sagittal
      balance improvement and cement leaking. Complications are rare but serious
      adverse events have been described, so caution should be exerted. Unilateral
      procedures should be pursued whenever feasible. Upcoming randomized trials (CEEP,
      OSTEO-6, STIC-2, and VERTOS IV) will provide the missing link. 

PMID- 24724109
TI  - Effect of Minor Amendments of Patient's Position on the Accuracy of Linear
      Measurements Yielded from Cone Beam Computed Tomography.
AB  - STATEMENT OF PROBLEM: Image distortion in intra and extra-oral radiographs are an
      unavoidable phenomenon. Patient's positional changes from the routine alignments
      is an important issue for this unwanted alteration, Therefore the accuracy of the
      dimensional measurements will be affected. PURPOSE: Our purpose is to find out
      the effect of minor changes (possibly happening in the clinic) in the position of
      a human dry skull on the accuracy of the measurements acquired by Cone Beam
      Computed Tomography (CBCT). MATERIALS AND METHOD: In this study, 3 locations on
      the skull were pointed with radio- opaque markers. Imaging process with Kodak
      9000 CBCT was performed in standard and 10 analytically miss- oriented positions.
      Then 2 distances were measured between the centers of markers. Later, these
      measurements were compared with the standard position values. RESULTS: There was
      not any imperative difference in the measurements of the 10 altered positions
      yielded in this study with standard position values. CONCLUSION: According to our
      results, apparently, the accuracy of linear measurements in CBCT images is
      endorsed by unintentional small changes in the patient's position during the
      projections.

PMID- 24724108
TI  - Implications of foot ulceration in hemodialysis patients: a 5-year observational
      study.
AB  - Foot ulceration (FU) remains a serious concern for patients worldwide. We
      analyzed the incidence, risk factors, and outcome of FU in hemodialysis (HD)
      patients. A retrospective cohort study was conducted for 252 HD patients who were
      followed up for 5 years. Patients were categorized according to whether they
      developed FU or not. The FU group (17%) was older and had significantly higher
      incidence of nephropathy, retinopathy, peripheral (PAD), coronary artery disease
      (CAD), and diabetes mellitus (DM) as compared to no-FU group. FU group had higher
      frequency of major amputation (P = 0.001) and HD vascular access (P = 0.01).
      Patients with combined DM and PAD had a 10-fold increased risk of FU in
      comparison to those who had DM alone. Presence of PAD was the main independent
      predictor for development of FU in HD with an adjusted odd ratio (aOR) of 16.0
      (95% CI: 4.41-62.18; P = 0.001). After adjusting for age, sex, and CAD,
      predictors for mortality were PAD (aOR 4.3), FU (aOR 3.6), and DM (aOR 2.6). FU
      is common in HD patients regardless of DM. However, the presence of PAD is
      significantly associated with more FU and mortality in HD. HD patients need
      intensive foot care and warrant progressive modification of vascular risk
      factors. 

PMID- 24724110
TI  - Awareness of Iranian's General Dentists Regarding the Latest Prophylaxis
      Guideline for Prevention of Infective Endocarditis.
AB  - Statement of Problem : Dental procedures leading to oral tissue injuries may
      provoke bacterial release to the blood stream causing infective endocarditis (IE)
      in vulnerable patients. The guideline which was proposed by AHA has been updated
      9 times having the last update published in 2007. This study was endeavored to
      uncover the level of knowledge of general dental practitioners in Shiraz,
      concerning the 2007 AHA guidelines for endocarditis prophylaxis in patients with
      cardiac problems receiving dental treatments. MATERIALS AND METHOD: This cross-
      sectional and descriptive analytical study included 150 dentists as participants.
      All practitioners were given a self -report questionnaire which consisted of
      three sections. Questions were designed to assess their knowledge of antibiotic
      prophylaxis in patients with cardiac disease. RESULTS: Almost all participants
      (93%) were aware of antibiotic prophylaxis to be essential for tooth extraction.
      Most participants did not believe in prophylaxis for noninvasive procedures (such
      as shedding of primary teeth, impression, intraoral radiography). From all of the
      respondents, 75% considered Amoxicillin to be the antibiotic of choice and 57%
      were acquainted with the correct dose of Amoxicillin for high risk patients.
      CONCLUSION: The study identified a potential for under/over prescription of
      antibiotic prophylaxis under the current guideline. Burden of IE necessitates
      more accurate knowledge of antibiotic prophylaxis in the undergraduate curriculum
      and continuing education programs of dentistry.

PMID- 24724111
TI  - Flexural strength of glass and polyethylene fiber combined with three different
      composites.
AB  - STATEMENT OF PROBLEM: The flexure of the fiber- reinforced composites (FRC) which
      can be generally used instead of fixed metal- framework prostheses have been more
      advocated due to the enormous demands for the conservative and esthetic
      restoration. The flexure of the fiber should be well-fitted to its covering
      composite. No study has been reported the comparison of the combination of glass
      and polyethylene fiber with particulate filled composite and fiber reinforced
      composite yet. PURPOSE: This study compared the flexural strength of two types of
      fibers combined with three types of composites. MATERIALS AND METHOD: Sixty-six
      specimens were prepared in a split mold (25*2*2 mm). The specimens were divided
      into six groups according to the type of resin and the fiber (N = 11): group 1:
      Z250 composite + Polyethylene fiber; group 2: Build It composite + Polyethylene
      fiber; group 3: Nulite F composite+ Polyethylene fiber; group 4: glass fiber +
      Z250 composite; group 5: glass fiber + Build-It composite and group 6: glass
      fiber + Nulite F. The mean flexural strengths (MPa) values were determined in a 3
      point bending test at a crosshead speed of 1 mm/min by a universal testing
      machine (Zwick/Roell Z020, Germany). The results were statistically analyzed,
      using one and two- way ANOVA and LSD post-hoc tests (p< 0.05). RESULTS: The
      highest flexural strength was registered for glass fiber in combination with Z250
      composite (500 MPa) and the lowest for polyethylene fiber in combination with
      Build-It composite (188 MPa). One-way ANOVA test revealed that there was no
      statistically significant difference between polyethylene fiber combinations (p=
      0.62) but there was a significant difference between glass fiber combinations (p=
      0.0001). Two-way ANOVA revealed that the fiber type had a significant effect on
      flexural strength (p= 0.0001). CONCLUSION: The choice of fiber and composite type
      was shown to have a significant positive influence on the flexural properties of
      the fiber-reinforced composite. Glass fiber has a significant influence on the
      flexural properties of directly- made specimens.

PMID- 24724112
TI  - Investigation of the awareness of the students of shiraz dental school concerning
      the patients' rights and the principles of ethics in dentistry.
AB  - STATEMENT OF PROBLEM: Deliberating the patients' rights is one of the major human
      ethical and legal principles which can be investigated through the agenda of
      professional and medical ethics.accordingly , the students of dentistry have to
      be educated about this issue and achieve the necessary skills in deliberating and
      concerning the patients' rights. PURPOSE: The present study aimed to investigate
      Shiraz dental students' awareness and attitude regarding the patients' rights as
      well as the principles of dental ethics in order to design methods for organizing
      and improving the ethics in dentistry. MATERIALS AND METHOD: The present
      descriptive-analytical study was conducted on 111 students of different
      departments of Shiraz Dental School. The study data were collected through a
      questionnaire designed based on the patients' rights charter in Iran, ADA ethical
      codes which are internationally acceptable in the field of dentistry, and the
      guidelines of the ministry of health, treatment, and medical education (No.
      140588). Then, the data were entered into the SPSS statistical software and
      analyzed. RESULTS: Of all participants, 21.6% were men and 78.4% were women.
      According to the results, 71% of the students were acquainted with the patients'
      rights. In addition, the patients' characteristics, including gender and
      nationality, were not important for 58.6% of the students. CONCLUSION: The study
      findings showed that 71% of the participants were acquainted with the patients'
      rights Establishment of a comprehensive, integrated charter in Iran is needed.
      With rapid development of medical sciences, new issues appear which necessitate
      taking into account the mutual rights of the physicians, people, and patients.

PMID- 24724113
TI  - Comparison of Apical Sealing Ability of Lateral Condensation Technique in Room
      and Body- Simulated Temperatures (An in vitro study).
AB  - STATEMENT OF PROBLEM: Studies reported that nearly 60% of endodontic failures
      have been attributed to inadequate obturation of the root canal system. Thus,
      complete obturation of the root canal system and proper apical seal are essential
      elements in the long-term success of root canal treatment. PURPOSE: This study
      aimed to compare the apical seal of lateral condensation technique in the room
      and in body- simulated temperature. MATERIALS AND METHOD: In this experimental
      study, 70 extracted, single- rooted, human premolar teeth were instrumented and
      divided up into four groups. All tooth's canals were obturated by lateral
      condensation technique except the teeth in the positive control group. Group 1and
      2, each with 30 teeth, were obturated in the room and intracanal temperature
      respectively. The other two groups were positive and negative control group each
      with 5 teeth. All groups except negative control were covered by two layers of
      nail polish. Then linear dye penetration was evaluated with a stereomicroscope.
      Data was analyzed with student-t test and also Kolmogorov- Smirnov Goodness- of-
      Fit test to make sure of data. RESULTS: RESULTS showed that dye penetration in
      group one (obturation in room temperature) was 0.6mm more than group 2
      (obturation in simulated-body temperature) although this was not statistically
      significant (p> 0.05). CONCLUSION: Under the condition of this invitro study,
      apical sealing ability was better in the body-simulated temperature than the room
      temperature, although it was not statistically significant.

PMID- 24724114
TI  - Comparison of MTA and CEM Cement Microleakage in Repairing Furcal Perforation, an
      In Vitro Study.
AB  - STATEMENT OF PROBLEM: Sealing the perforation defect is an important factor to
      reduce inflammation in the area and to perform healing. Selecting the appropriate
      material to repair the defect is an important concern. Among the various
      available materials, MTA and CEM are used recently for achieving this purpose. In
      the current study we compare the sealing ability of these materials by evaluating
      their microleakage by fluid filtration method. PURPOSE: The purpose of this study
      was to compare the microleakage of MTA and CEM cement in furcal perforation in
      different periods of time. MATERIALS AND METHOD: Forty one mandibular molars were
      selected for this experimental study. The perforation defects were created
      perpendicular to the long axis of the teeth, on the furcation of the teeth and
      the samples were divided into 2 experimental and two control groups. The defects
      were sealed by CEM and MTA in each experimental group. The samples were undergone
      the fluid filtration test with 20 cm H2O pressure. The amount of fluid filtration
      was measured for each sample at 24, 72 and 168 hrs and the data were analyzed by
      using ANOVA and T test. RESULTS: The experimental groups which were sealed with
      CEM exhibited significantly less microleakage in all determined periods of time
      (24, 72 and 168 hrs) than MTA groups (p< 0.001). CONCLUSION: Based on the results
      of this study, CEM cement has a better sealing ability compared with MTA using
      fluid filtration method.

PMID- 24724115
TI  - Association of dental practice as a risk factor in the development of carpal
      tunnel syndrome.
AB  - STATEMENT OF PROBLEM: Carpal tunnel syndrome (CTS) is an important cause of work
      disability. There is controversy over the relation between carpal tunnel syndrome
      and occupation. The aim of this study was to assess the relationship between the
      time-span of practicing dentistry and the role of dominant hands in the
      development of carpal tunnel syndrome. MATERIALS AND METHOD: In this descriptive
      cross sectional study, 40 dentists and dental students (15 women and 25 men)
      undertook the electroneuro-diagnostic test in both hands by an electromyogram
      (EMG) and they were also evaluated in terms of self- reported clinical symptoms.
      RESULTS: 17.5% of participants were diagnosed to have decreased nerve conduction
      velocity while10% had reported clinical symptoms of CTS. Both dominant and non
      dominant hands were involved. Within cases who were diagnosed as having median
      nerve neuropathy, 87.5% worked more than 20 hours per week. 57% had 17-23 years
      of dental practice experience and 14.2% of cases had10-16 years of practice in
      dentistry. CONCLUSION: The high rate of CTS symptoms, in both dominant and non
      dominant hand among dental practitioners with more years of dental practice,
      indicates a prequisite for particular attention, then sufficient education on the
      major risk factors causing this problem. Early diagnosis of these symptoms may
      improve the future management of the disease.

PMID- 24724116
TI  - Odontogenic myxoma of maxilla in an atypical location: a case report.
AB  - Odontogenic myxoma is a rare and locally invasive benign neoplasm found
      exclusively in jaws. It presents local invasiveness and tendency to recurrence.
      According to the World Health Organization (WHO), the odontogenic myxoma is
      classified as an odontogenic tumor of ectomesenchymal origin. The odontogenic
      myxoma is a rare entity found in both jaws while the mandible is involved more
      commonly than the maxilla. We present a kind of odontogenic myxoma in a 24-year
      old male that was found in an unusual location. 

PMID- 24724117
TI  - Mucocele accompanied by a traumatic neuroma: a case report.
AB  - Mucocele and traumatic neuroma are two lesions related to the traumatic events;
      however there is only one reported case in which these two entities were
      perceived simultaneously. The current study reported a 21-year-old man who
      complained of painless recurrent swelling, accompanied by paresthesia on his left
      lower labial mucosa. He had a previous history of similar lesion and had been
      treated with surgery and cauterization last year. The primary clinical impression
      was a recurrent mucocele. Microscopic surveys displayed a traumatic neuroma in
      the vicinity of a mucocele which seems to be arising from the previous surgical
      treatment. 

PMID- 24724118
TI  - A Clinical Practice Update on the Latest AAOS/ADA Guideline (December 2012) on
      Prevention of Orthopaedic Implant Infection in Dental Patients.
AB  - The American Academy of Orthopaedic Surgeons (AAOS) and the American Dental
      Association (ADA), along with 10 other academic associations and societies
      recently (December 2012) published their mutual clinical practice guideline
      "Prevention of Orthopaedic Implant Infection in Patients Undergoing Dental
      Procedures." This evidence-based guideline ,detailed in 325 pages, has three
      recommendations and substitutes the previous AAOS guideline. The new published
      clinical guideline is a protocol to prevent patients undertaking dental
      procedures from orthopaedic implant infection. The guideline is developed on the
      basis of a collaborative systematic review to provide practical advice for
      training clinicians, dentists and any qualified physicians who need to consider
      prevention of orthopaedic implant (prosthesis) infection in their patients. This
      systematic review found no explicit evidence of cause-and-effect relationship
      between dental procedures and periprosthetic joint infection (PJI). This LTTE
      wishes to present a vivid summary of AAOS/ADA clinical practice guideline as a
      clinical update and an academic implementation to inform and assist Iranian
      competent clinicians and dentists in the course of their treatment decisions, to
      enrich the value and quality of health care on the latest international basis. 

PMID- 24724119
TI  - Parotid Duct Repair by Facial Vein Graft versus Gore-Tex, A Sialographic
      Evaluation.
AB  - STATEMENT OF PROBLEM: The most common method for parotid duct anastomosis is
      suturing. A ductal defect of greater than 1cm may prevent a direct anastomosis.
      PURPOSE: The goal of this study was a sialographic evaluation to compare
      repairing a parotid duct with facial vein graft versus Gore-Tex tub in 19 dogs.
      MATERIAL AND METHODS: Nineteen dogs were studied in this experimental trial.
      Extra oral transverse incisions were made in buccal regions bilaterally to expose
      parotid ducts and a defect (2 cm) was performed in similar areas (right and
      left). The right resected duct was repaired with facial vein graft and the left
      anastomosis was performed by using the Gore-Tex tube microscopically. Sialography
      was used to evaluate the ductal leakage. Statistical analysis was performed,
      using SPSS software and McNemar's test. RESULTS: Based on the sialography
      evaluation; the ductal leakage was seen in five cases (26.31%) on the right side
      and in seven cases (36.84%) in the left side. Statistical analysis using
      McNemar's test suggested no statistically significant difference between ductal
      leakages in right and left parotid ducts (p> 0.05). CONCLUSION: The results of
      this study suggest that the efficacies of Gore-Tex tube and vein graft in parotid
      duct anastomosis are similar, but the use of Gore-Tex tube had a number of
      advantages, including reduced morbidity of the graft and short operation time.

PMID- 24724120
TI  - Film thickness and flow properties of resin-based cements at different
      temperatures.
AB  - STATEMENT OF PROBLEM: For a luting agent to allow complete seating of prosthetic
      restorations, it must obtain an appropriate flow rate maintaining a minimum film
      thickness. The performance of recently introduced luting agents in this regard
      has not been evaluated. PURPOSE: To measure and compare the film thickness and
      flow properties of seven resin-containing luting cements at different
      temperatures (37 degrees C, 25 degrees C and10 degrees C). MATERIAL AND METHODS:
      Specimens were prepared from five resin luting cements; seT (SDI), Panavia F
      (Kuraray), Varioloink II (Ivoclar), Maxcem (Kerr), Nexus2 (Kerr) and two resin
      modified glass-ionomer luting cements (RM-GICs); GC Fuji Plus (GC Corporation),
      and RelyX Luting 2 (3 M/ESPE). The film thickness and flow rate of each cement
      (n=15) was determined using the test described in ISO at three different
      temperatures. RESULTS: There was a linear correlation between film thickness and
      flow rate for most of the materials. Cooling increased fluidity of almost all
      materials while the effect of temperature on film thickness was material
      dependent. At 37 degrees C, all products revealed a film thickness of less than
      25um except for GC Fuji Plus. At 25 degrees C, all cements produced a film
      thickness of less than 27 um except for seT. At 10 degrees C, apart from seT and
      Rely X Luting 2, the remaining cements showed a film thickness smaller than 20
      um. CONCLUSION: Cooling increased fluidity of almost all materials, however. the
      film thickness did not exceed 35 um in either condition, in spite of the lowest
      film thickness being demonstrated at the lowest temperature.

PMID- 24724121
TI  - Effects of three Commercial Mouth Rinses on the Cultured Fibroblasts: An in Vitro
      Study.
AB  - STATEMENT OF PROBLEMS: An ideal antimicrobial agent should have minimal cytotoxic
      effect to host cells. PURPOSE: The aim of this study was to determine the
      cytotoxic effect of three commercial mouthwashes (Chlorhexidine, Persica and
      Irsha) on the cultured fibroblasts. MATERIAL AND METHODS: For determining the
      cytotoxic effect of Irsha, Chlorhexidine and Persica, uninfected cells were grown
      in the absence and presence of various concentration (2,4,8,16,32,64,128) of
      these mouth washes for 1, 2, 3 and 4 days. RESULTS: In this study, three mouth
      washes show cytotoxic effect on the cultured cells, at commercially available
      concentration and even diluted and Irsha was found to be the most toxic one.
      Cytotoxicity of three mouthwashes was reduced with decreasing concentration.

PMID- 24724122
TI  - The efficacy of passiflora incarnata linnaeus in reducing dental anxiety in
      patients undergoing periodontal treatment.
AB  - STATEMENT OF PROBLEM: Oral premedication used to reduce the anxiety in patients
      undergoing dental treatment. Passion flower has been used as a sedative that can
      control the dental anxiety. PURPOSE: This study determines the efficacy of
      Passion flower, in reducing anxiety during the dental procedures. MATERIAL AND
      METHODS: In this randomized- one sided blind clinical trial, 63 patients, with
      moderate, high and severe anxiety(according to VAS score) in need of periodontal
      treatment were randomly divided into 3 groups of 21.The first group was given the
      drop Passion flower drop and the second group were given the drop of placebo and
      the third group; neither drug nor placebo were given (negative control group).
      RESULTS were analyzed by Chi Square, Variance Analysis, Tucky and Paired-T using
      SPSS software. RESULTS: Mean anxiety level prior to the drug administration was
      12.09+/-2.42 for the Passion flower group, 12.00+/-2.66 for the placebo group and
      11.66+/-2.39 for the negative control group. After premedication, these values
      were: 8.47+/-2.58 for the Passion flower group, 10.52+/-2.11 for the placebo
      group and 11.23+/-2.34 for the negative control group. These results demonstrated
      a significant difference (p< 0.0001) in the anxiety levels before and after the
      Passion flower administration in the Passion flower group and also between the
      Passion flower group and the other two groups. CONCLUSION: RESULTS indicated that
      administration of Passion flower, as a premedication, is significantly effective
      in reducing the anxiety. Since this study is a pioneer on the subject, further
      trials with greater number of subjects are required to confirm our results.

PMID- 24724123
TI  - A Comparative Study on Micro Hardness and Structural Changes of Dentin Floor
      Cavity Prepared by Er: YAG Laser Irradiation and Mechanical Bur.
AB  - STATEMENT OF PROBLEM: Laser irradiation makes structural and chemical changes on
      the dental hard tissues. These changes alter the level of solubility and
      permeability of dentin. PURPOSE: The aim of this study was to compare the
      microhardness and the structural changes in the dentin cavity floor prepared with
      Er: YAG laser and bur. MATERIAL AND METHODS: In this experimental study, fifteen
      intact human molars were selected. Two square cavities were prepared on the
      buccal and lingual surfaces of each tooth. One side was randomly prepared by
      Er:YAG laser and the other side by bur. The specimens were divided into two
      halves. Consequently, there were 30 samples in every group. One half was assigned
      for the Vickers's hardness test and the other one, for determination of Ca and P
      percentage and atomic elements analysis. The data were analyzed by Paired T-tests
      through SPSS16 (alpha<=o.o5). RESULTS: The means and the standard deviation of
      the microhardness were 69.77+/-25.62 and 51.33+/-9.31 Kg/mm(2) in the laser and
      bur groups, respectively. Statistical analysis showed significant differences
      between the two groups (p=0.017). Weight percentage of calcium in the laser
      cavity (65.5) was less than the bur cavities (68.21) and the difference was
      significant (p= 0.037). CONCLUSION: The hardness of dentin in laser group was
      higher than the bur group because of the higher mineral content of the dentin.
      The hardness and the mineral content of dentin are important factors in the
      bonding effectiveness of the dental materials so with laser cavity preparation,
      good mineral substrate are available for a better bonding.

PMID- 24724124
TI  - Root and canal morphology of mandibular second molar in an Iranian population by
      clearing method.
AB  - STATEMENT OF PROBLEM: The knowledge of the pulp anatomy plays an important role
      in the success of endodontic treatments. PURPOSE: The aim of this study was to
      determine the root and canal morphology of the mandibular second molar teeth in
      an Iranian population. MATERIAL AND METHODS: One hundred intact human mandibular
      second molars were collected. The teeth were examined visually and the number of
      their roots were recorded. The teeth were covered using of lacquer. Access
      cavities were prepared and the pulp tissue was dissolved by sodium hypochlorite.
      The apices were covered with the glue and the root canals were injected with the
      methylene blue and were decalcified with 10% nitric acid, dehydrated with
      ascending concentrations of alcohol and rendered clear by immersion in methyl
      salicylate. The following remarks were evaluated: (i) number of root canals per
      tooth; (ii) number of canals per root; (iii) canal configuration in each root.
      RESULTS: Of 100 examined teeth; 6% had one root, 89% had two roots, 2% had three
      roots and 3% had C-shaped roots. The teeth were classified based on the number of
      canals: 3 % had single canal, 6 % two canals, 54% three canals, 34% four canals,
      whilst 3 % had C-shaped roots. Based on the Vertucci classification, the most
      prevalent canal configuration in the mesial root was type II and in the distal
      root was type I. Conclusion : Iranian mandibular second molar teeth exhibit
      features which are similar to the average Jordanian, Caucasian and Burmese root
      and canal morphology.

PMID- 24724125
TI  - Investigation of the Relationship between the Increase in the Intercanine width
      and the Children's Facial Parameters; a 6-month Follow-up Study.
AB  - The present study, as a pilot study, aimed to investigate the increase in the
      intercanine width in different facial forms to predict the amount of future
      increase in the intercanine width. The results of the pilot study showed that the
      intercanine width increased more in the boys with wider faces while this
      relationship was not observed in the girls. Based on the results of this
      preliminary study, the girls' facial width could not be considered as a
      determining criterion in evaluation of the amount of increase in the intercanine
      width. 

PMID- 24724126
TI  - Force eruption of mandibular second incisor in an 11- year old boy: a technical
      report.
AB  - There is a great challenge in the treatment of deeply fractured and un-restorable
      teeth among dentists. Orthodontic force eruption is a method of treatment for
      these teeth to preserve natural root system and periodontal structures. This
      technical report is a new modification of this procedure presented in an 11- year
      old boy with deeply fractured left second mandibular incisor. The fractured teeth
      were treated with root canal therapy and a file #80 was modified to become a hook
      cemented into the fractured tooth. Anterior teeth were splinted and used as
      anchorage to help the root extrusion. 1-year follow up of the tooth showed the
      convenience of the treatment. This simple and low-cost method can be an
      acceptable alternative to the current high cost techniques, achieving the same
      results. 

PMID- 24724127
TI  - A maxillary second molar with two separate palatal roots: a case report.
AB  - Variations of dental root canals were reported by different authors. One of the
      rare variations is the presence of two separate palatal roots of maxillary
      molars, especially second maxillary molars. This case study reported a maxillary
      second molar with two separate palatal roots and a palatal bifurcation which was
      found during the periodontal flap surgery. Although these variations are rare,
      awareness of their presence would help in successful periodontal and endodontic
      treatment. 

PMID- 24724128
TI  - Letter to editor.

PMID- 24724129
TI  - Microleakage of Posterior Composite Restorations with Fiber Inserts Using two
      Adhesives after ging.
AB  - STATEMENT OF PROBLEM: Microleakage is one of the most frequent problems
      associated with resin composites, especially at the gingival margin of posterior
      restorations. Insertion of fibers in composite restorations can reduce the total
      amount of composite and help to decrease the shrinkage. PURPOSE: The aim of this
      study was to evaluate the effect of polyethylene fiber inserts on gingival
      microleakage of class II composite restorations using two different adhesive
      systems. MATERIALS AND METHOD: In this experimental study, class II cavities were
      prepared on 60 premolars. The gingival floor was located 1.0 mm below the CEJ.
      Dimension of each cavity were 3 mm buccolingually and 1.5 mm in axial depth. The
      specimens were divided into 4 groups according to the adhesive type and fiber
      insert (n=4). Single bond and Clearfill SE bond and Filtek p60 were used to
      restore the cavities. In groups without fiber inserts composite was adapted onto
      cavities using layering technique. For cavities with fiber inserts, 3 mm piece of
      fiber insert was placed onto the composite increment and cured. The specimens
      were stored in distilled water at 37(o)C for 6 months. All specimens were
      subjected to 3000 thermo-cycling. The tooth surfaces except for 1 mm around the
      restoration margins covered with two layers of nail varnish .The teeth were
      immersed in 2% Basic Fuchsin for 24 hours, then rinsed and sectioned
      mesiodistally. The microleakage was determined under a stereomicroscope (40X).
      Data were statistically analyzed by Kruskal-wallis and Mann-Whitney U tests (p<
      0.05). RESULTS: The Kruskal-Wallis test revealed no significant differences in
      mean microleakage scores among all groups (p= 0.281). CONCLUSION: Use of
      polyethylene fiber inserts and etch-and-rinse and self-etch adhesives had no
      effect on microleakage in class II resin composite restorations with gingival
      margins below the CEJ after 6- month water storage.

PMID- 24724130
TI  - Comparison of Dimensional Accuracy between Open-Tray and Closed-Tray Implant
      Impression Technique in 15 degrees  Angled Implants.
AB  - STATEMENT OF PROBLEM: Various impression techniques have different effects on the
      accuracy of final cast dimensions. Meanwhile; there are some controversies about
      the best technique. PURPOSE: This study was performed to compare two kinds of
      implant impression methods (open tray and closed tray) on 15 degree angled
      implants. MATERIALS AND METHOD: In this experimental study, a steel model with 8
      cm in diameter and 3 cm in height were produced with 3 holes devised inside to
      stabilize 3 implants. The central implant was straight and the other two implants
      were 15 degrees  angled. The two angled implants had 5 cm distance from each
      other and 3.5 cm from the central implant. Dental stone, high strength (type IV)
      was used for the main casts. Impression trays were filled with poly ether, and
      then the two impression techniques (open tray and closed tray) were compared. To
      evaluate positions of the implants, each cast was analyzed by CMM device in 3
      dimensions (x,y,z). Differences in the measurements obtained from final casts and
      laboratory model were analyzed using t-Test. RESULTS: The obtained results
      indicated that closed tray impression technique was significantly different in
      dimensional accuracy when compared with open tray method. Dimensional changes
      were 129 +/- 37MU and 143.5 +/- 43.67MU in closed tray and open tray, while
      coefficient of variation in closed- tray and open tray were reported to be 27.2%
      and 30.4%, respectively. CONCLUSION: Closed impression technique had less
      dimensional changes in comparison with open tray method, so this study suggests
      that closed tray impression technique is more accurate.

PMID- 24724131
TI  - A Comparison of pical Root Resorption in Incisors after Fixed Orthodontic
      Treatment with Standard Edgewise and Straight Wire (MBT) Method.
AB  - STATEMENT OF PROBLEM: One of the major outcomes of orthodontic treatment is the
      apical root resorption of teeth moved during the treatment. Identifying the
      possible risk factors, are necessary for every orthodontist. PURPOSE: The aim of
      this study was to compare the rate of apical root resorption after fixed
      orthodontic treatment with standard edgewise and straight wire (MBT) method, and
      also to evaluate other factors effecting the rate of root resorption in
      orthodontic treatments. MATERIALS AND METHOD: In this study, parallel periapical
      radiographs of 127 patients imaging a total of 737 individual teeth, were
      collected. A total of 76 patients were treated by standard edgewise and 51
      patients by straight wire method. The periapical radiographs were scanned and
      then the percentage of root resorption was calculated by Photoshop software. The
      data were analyzed by Paired-Samples t-test and the Generalized Linear Model
      adopting the SPSS 15.0. RESULTS: In patients treated with straight wire method
      (MBT), mean root resorption was 18.26% compared to 14.82% in patients treated
      with standard edgewise technique (p< .05). Male patients had higher rate of root
      resorption,statistically significant (p< .05). Age at onset of treatment,
      duration of treatment, type of dental occlusion, premolar extractions and the use
      of intermaxillary elastics had no significant effect on the root resorption in
      this study. CONCLUSION: Having more root resorption in the straight wire method
      and less in the standard edgewise technique can be attributed to more root
      movement in pre-adjusted MBT technique due to the brackets employed in this
      method.

PMID- 24724132
TI  - Effect of a Combined Bleaching Regimen on the Microhardness of a Sealed
      Methacrylate-based and a Silorane-based Composite.
AB  - STATEMENT OF PROBLEM: The use of tooth bleaching agents has been very popular
      treatment in dentistry. The bleaching agents have an inherent potential to impair
      surface properties of existing composite resin restorations. PURPOSE: This study
      evaluated the effect of a combined bleaching regimen on the surface microhardness
      of a Silorane-based and a sealed methacrylate-based composite. MATERIALS AND
      METHOD: Forty-five specimens of methacrylate-based composite (Ice) and 18
      specimens of Silorane composite (Filtek Silorane, 3M ESPE; USA) were prepared and
      randomly divided into 5 (1-5) and 2 (6-7) groups (n=9), respectively. After 8
      week aging, groups 1 and 6 were remained with no treatment. In groups 2, 4 and 5,
      the specimens were covered by a surface sealant and light cured. In groups 3, 4,
      5 and 7, the specimens were bleached with hydrogen peroxide 40% and then
      carbamide peroxide 20% for seven days. In group 5, after bleaching, the sealant
      was removed by polishing. Surface microhardness was measured and the data were
      analyzed using one-way ANOVA and Tukey tests (alpha=0.05). RESULTS: The
      microhardness values of groups 2 to 4 were significantly lower than that of
      group1 (p <0.05). There was no significant difference among groups 1, 5, 6 and 7
      (p> 0.05). CONCLUSION: The combined bleaching regimen used in this study had a
      substantial negative effect on methacrylate and sealed methacrylate composites
      but not on Silorane composite. Polishing following the bleaching on the sealed
      composite yielded a hardness value similar to that of unsealed methacrylate
      composite (control).

PMID- 24724133
TI  - Comparison the Marginal and Internal Fit of Metal Copings Cast from Wax Patterns
      Fabricated by CAD/CAM and Conventional Wax up Techniques.
AB  - STATEMENT OF PROBLEM: Metal-ceramic crowns are most commonly used as the complete
      coverage restorations in clinical daily use. Disadvantages of conventional hand
      made wax-patterns introduce some alternative ways by means of CAD/CAM
      technologies. PURPOSE: This study compares the marginal and internal fit of
      copings cast from CAD/CAM and conventional fabricated wax-patterns. MATERIALS AND
      METHOD: Twenty-four standardized brass dies were prepared and randomly divided
      into 2 groups according to the wax-patterns fabrication method (CAD/CAM technique
      and conventional method) (n=12). All the wax-patterns were fabricated in a
      standard fashion by means of contour, thickness and internal relief (M1-M12:
      representative of CAD/CAM group, C1-C12: representative of conventional group).
      CAD/CAM milling machine (Cori TEC 340i; imes-icore GmbH, Eiterfeld, Germany) was
      used to fabricate the CAD/CAM group wax-patterns. The copings cast from 24 wax
      patterns were cemented to the corresponding dies. For all the coping-die
      assemblies cross-sectional technique was used to evaluate the marginal and
      internal fit at 15 points. The Student's t- test was used for statistical
      analysis (alpha=0.05). RESULTS: The overall mean (SD) for absolute marginal
      discrepancy (AMD) was 254.46 (25.10) um for CAD/CAM group and 88.08(10.67) um for
      conventional group (control). The overall mean of internal gap total (IGT) was
      110.77(5.92) um for CAD/CAM group and 76.90 (10.17) um for conventional group.
      The Student's t-test revealed significant differences between 2 groups. Marginal
      and internal gaps were found to be significantly higher at all measured areas in
      CAD/CAM group than conventional group (p< 0.001). CONCLUSION: Within limitations
      of this study, conventional method of wax-pattern fabrication produced copings
      with significantly better marginal and internal fit than CAD/CAM (machine-milled)
      technique. All the factors for 2 groups were standardized except wax pattern
      fabrication technique, therefore, only the conventional group results in copings
      with clinically acceptable margins of less than 120um.

PMID- 24724134
TI  - Comparison of the Effect of two Denture Cleansers on Tensile bond Strength of a
      Denture Liner.
AB  - STATEMENT OF PROBLEM: One of the most clinical challenging issues in
      prosthodontics is debonding of soft liners from the denture base. PURPOSE: The
      aim of this study was to evaluate and compare tensile bond strength between soft
      liner and heat-cured acrylic resin when immersed in two different types of
      denture cleanser and distilled water, at different period of times. MATERIALS AND
      METHOD: In this experimental in vivo study, 238 heat-cured acrylic blocks were
      made. A soft liner was embedded between the acrylic blocks. Samples were divided
      into four groups: 17 samples were in the control group and were not soaked in any
      solution .The remaining samples were divided into 3 groups (Distilled water,
      Calgon and Fittydent). Each group was then subdivided into two subcategories,
      regarding the immersion time variable; 15 and 45 minutes. All samples were placed
      in tension force and tensile bond strength was recorded with the testing machine.
      One- way ANOVA and Tucky HSD post-hoc test were adopted to analyze the yielded
      data (alpha> 0.05). RESULTS: Specimens which were immersed in two denture
      cleansers (Fittydent and Calgon) and in distilled water showed significant
      difference (p= 0.001) in bonding strength when compared to the control group. The
      subjects immersed in denture cleanser solutions and distilled water did not
      reveal any significant difference (p= 0.90). For all groups; most of the bonding
      failures (72%) were cohesive type. CONCLUSION: The effect of the denture
      cleansers and distilled water on the bond strength was not statistically
      different; however, the difference was significant between the immersed groups
      with the non-immersed group. Moreover, type of the denture cleanser did not show
      any effect on the tensile strength. The tensile strength increases with time of
      immersion.

PMID- 24724135
TI  - Dentin hypersensitivity: etiology, diagnosis and treatment; a literature review.
AB  - The objective of this review is to inform practitioners about dentin
      hypersensitivity (DH); to provide a brief overview of the diagnosis, etiology and
      clinical management of dentin hypersensitivity and to discuss technical
      approaches to relieve sensitivity. This clinical information is described in the
      context of the underlying biology. The author used PUBMED to find relevant
      English-language literature published in the period 1999 to 2010. The author used
      combinations of the search terms "dentin*", "tooth", "teeth", "hypersensit*",
      "desensitiz*". Abstracts and also full text articles to identify studies
      describing etiology, prevalence, clinical features, controlled clinical trials of
      treatments and relevant laboratory research on mechanisms of action were used. 

PMID- 24724136
TI  - Delay in the diagnosis and treatment of oral cancer.
AB  - STATEMENT OF PROBLEM: Oral and pharyngeal cancer is one of the most mortal
      cancers; however, its quick diagnosis and referral is a crucial factor in
      enhancing the survival rate of the patients. PURPOSE: The aim of this study was
      to inspect the referral conditions and the reasons for the delay in curing the
      patients referred to the educational hospitals in Tehran. MATERIALS AND METHOD:
      In this retrospective -descriptive study, two hundred and fifty six files related
      to the oral and pharyngeal cancer were inspected. The documents were obtained
      from 5 educational hospitals specialized in the field of cancers. Eventually data
      related to the time difference between the first time of attending to lesion and
      diagnosing the cancer as patient's delay and until the curing as professional's
      delay were recorded. RESULTS: The majority of cancers were squamous cell
      carcinoma (SCC). The patient's delay was recorded in 110 files among the whole
      files. The mean of the time between the patients' first notice of the problem and
      the time visiting a primary care clinician was 270 days (range, 0-2520 days). The
      mean of the time from when the patient visited a primary- care clinician to the
      starting time of definitive treatment was 90 days (range, 0-270 days).
      CONCLUSION: In this study, like other studies, SCC was the most common occurring
      cancer. Delays related to the patients were more than those related to the
      professionals. And at last, accuracy in recording the files and training the
      patients were recognized to be the most imperative factors to continue the
      treatment successfully.

PMID- 24724137
TI  - Non-syndromic multiple odontogenic keratocyst: a case report.
AB  - Odontogenic keratocyst (OKC) is a common developmental odontogenic cyst affecting
      the maxillofacial region. Multiple OKCs are usually seen in association with
      nevoid basal cell carcinoma syndrome (NBCCS) but approximately 5% of patients
      with OKC have multiple cysts without concomitant syndromic presentation. This
      report represents a case of multiple OKCs in a non-syndromic patient. 

PMID- 24724138
TI  - Copper ion as a new leakage tracer.
AB  - STATEMENT OF PROBLEM: Most failures of root canal treatments are caused by
      bacteria. Studies showed that the most common cause of endodontic failures were
      the incomplete obturation of the root canal and the lack of adequate apical seal.
      Some in-vitro methods are used to estimate sealing quality, generally by
      measuring microleakage that allows the tracer agent to penetrate the filled
      canal. PURPOSE: Conventional methods of evaluating the seal of endodontically
      treated teeth are complicated and have some drawbacks. We used copper ion
      diffusion method to assess the leakage and the results were compared to dye
      penetration method. MATERIALS AND METHOD: The crowns of 21 extracted teeth were
      cut off at the CEJ level. After preparing the canals, the teeth were placed in
      tubes containing saline. They were divided randomly into 15 experimental cases; 3
      positive and 3 negative controls. Positive controls were filled by single cone
      without sealer while the experimental and the negative control groups were filled
      by lateral technique. The coronal portion of gutta was removed and 9mm was left.
      The external surface of each tooth was coated with nail polish. Two millimeters
      of apical portion was immersed into 9ml of distilled water and 0.3ml of CuSO4
      solution was injected into the coronal portion. After 2 days, copper sulfate was
      measured by an atomic absorption spectrophotometer. The teeth were then immersed
      in 2% methylene blue for 24 hours, sectioned and the extent of dye penetration
      was measured by a stereomicroscope. RESULTS: The maximum and minimum recorded
      copper ion concentrations for the experimental group were 18.37 and 2.87ppm
      respectively. The maximum and minimum recorded dye penetrations for the
      experimental group were 8.5 and 3.5mm respectively. The statistical analysis,
      adopting paired samples test, showed poor correlation between average recorded
      results of two methods. CONCLUSION: Based on our results, there was no
      significant correlation between the dye penetration and the copper ion diffusion
      methods.

PMID- 24724139
TI  - Prevalence of root dilaceration in adult patients referred to shiraz dental
      school (2005-2010).
AB  - STATEMENT OF PROBLEM: Dilaceration is defined as a sudden change in the axial
      inclination of root or between the crown and the root of a tooth. There is no
      previous study evaluating its prevalence in south of Iran. PURPOSE: This study
      evaluates the prevalence of root dilaceration on the basis of its location in
      dental arch in a sample of dental patients referring to Shiraz dental school,
      Iran. MATERIALS AND METHOD: This retrospective study was performed using full
      mouth periapical radiographs of 250 patients who were referred to Shiraz dental
      school. Buccal and lingual dilaceration was determined by its known" bull's eye"
      appearance in the radiographs or if the deviation was in the mesial or distal
      directions; the angle of 90 degree or greater between the deviation and the axis
      of root was the inclusion criteria. RESULTS: Root dilaceration was detected in
      0.3% of teeth and 7.2% of patients. It was distributed equally between the
      maxilla and mandible. Mandibular second molar was the most frequent dilacerated
      tooth (1.6%) followed by maxillary first molar (1.3%) and mandibular first molar
      (0.6%). The alveolar nerve was the most common anatomic structure near
      dilacerated teeth. CONCLUSION: According to this study, root dilaceration is an
      uncommon developmental anomaly which occurs mostly in the posterior teeth.

PMID- 24724140
TI  - Assessment of dental maturity of children aged 7-15 years using demirjian method
      in a selected Iranian population.
AB  - STATEMENT OF PROBLEMS: Dental age can be estimated on the basis of the tooth
      mineralization level during the developmental process of the teeth. Among various
      radiological methods reported for the dental age determination in children,
      Demirjian method is widely used. PURPOSE: To evaluate the applicability of
      Demirjian method in age estimation of the children aged 7-15 years in Babol, a
      northern city of Iran. MATERIALS AND METHOD: A cross sectional study was
      performed on the panoramic radiographs of 168 individuals with 7-15 years old.
      Maturation of the seven permanent teeth on the left side of the mandible was
      determined according to the crown and root development stages; described by
      Demirjian method. The mean of the dental age (DA) according to the Demirjian was
      compared to the mean of chronological age (CA). Data were collected and analyzed
      using SPSS, V18. P-values<0.05 were considered significance. RESULTS: The mean
      and the SD of CA was 11.06+/-2.29 (boys: 11.08+/-2.31, girls: 11.03+/-2.28). The
      mean and the SD of DA was 11.44+/-2.85 (boys: 11.81+/-2.93, girls: 11.08+/-2.73)
      and the mean and the SD of DA minus CA for all of the children were 0.38+/-1.24
      (boys: 0.72+/-1.2, girls: 0.05+/-1.21). Also, t-Test analysis showed the
      differences of the mean value of the estimated - chronological age difference was
      statistically significant between the boys and the girls group (p< 0.001).
      CONCLUSION: Considering the determined differences between estimated dental age
      and chronological age in this study; Demirjian method can be applicable for
      estimation of dental age in girls and boys before their puberty in northern of
      Iran.

PMID- 24724141
TI  - A clinicopathological survey of Basal cell carcinoma in an Iranian population.
AB  - STATEMENT OF PROBLEM: Basal cell carcinoma (BCC), the most common skin cancer, is
      a locally invasive malignant epidermal tumor with ulceration and destruction of
      underlying structures. PURPOSE: The purpose of this study was clinicopathological
      evaluation of BCC in the state and the private pathology centers in Hamadan
      province during 1990-2010. MATERIALS AND METHOD: In this retrospective study all
      histopathologically proven cases of BCC were reviewed and the related information
      including age, gender, place of residency and number of tumors for the patients
      alongside with the site of occurrence, size, histopathological and clinical type
      of the lesions were collected and then statistically analyzed, using SPSS
      software. RESULTS: A total of 804 incidents of BCC were diagnosed in 746 patients
      (296 females and 450 males) with the most affected site being in the head-face
      (84.8%), neck (2.6%), trunk (1.6%) and limbs (0.9 %) and 10.1% cases with unknown
      site. The mean age for the patients was 61.77+/-13.75 years (63.07+/- 13.44 for
      males, 59.81 +/- 14.01 for females) and the highest frequency (27.2%) occurred
      among 60-69 years age group. Nodular type was the most common clinical and
      histopathological BCC lesions studied whereas the mean size of the lesions was
      15.67 +/- 11.06 mm with more frequency rate in urban than rural regions.
      CONCLUSION: This study focuses on the survey of BCC in Hamadan province but
      regarding to insufficiency of the data collected by state and provincial
      pathology centers about the BCC cases reported; it is highly recommended to apply
      comprehensive questionnaire, which are designated by skillful professionals who
      are familiar with the lesion nationally.

PMID- 24724142
TI  - Effect of beverages on the hardness and tensile bond strength of temporary
      acrylic soft liners to acrylic resin denture base.
AB  - STATEMENT OF PROBLEM: Two potential problems commonly identified with a denture
      base incorporating a resilient liner are failure of the bond between acrylic
      resin and soft liner material, and loss of resiliency of the soft liner over
      time. Since patients may drink different beverages, it is important to evaluate
      their effects on physical properties of soft lining materials. PURPOSE: The
      objective of this in vitro study was to evaluate the effect of different
      beverages on the hardness of two temporary acrylic-based soft lining materials
      and their bond strength to the denture base resin. MATERIALS AND METHOD: For the
      hardness test; a total of 80 rectangular specimens (40mm*10mm*3mm) were
      fabricated from a heat-polymerized polymethylmethacrylate. Two commercially auto
      polymerized acrylic resin-based resilient liners; Coe-Soft and Visco-gel were
      prepared according to the manufacturers' instructions and applied on the
      specimens. For the tensile test, 160 cylindrical specimens (30mm*10mm) were
      prepared. The liners were added between specimens with a thickness of 3 mm. The
      specimens of both soft liners were divided into 4 groups (n=10) and immersed in
      distilled water as the control group, Coca-Cola, 8% and 50% ethanol. All groups
      were stored in separate containers at 37(o)C for 12 days. All beverages were
      changed daily. The hardness was determined using a Shore A durometer and tensile
      bond strength was determined in a ZwickRoell testing machine at a cross-head
      speed of 5mm/min. The results were analyzed using two-way ANOVA. RESULTS: There
      was no significant interaction between the soft liners and the drinks for both
      hardness (p= 0.748) and bond strength (p= 0.902). There were statistically
      significant differences between all drinks for both hardness (p< 0.001) and bond
      strength (p< 0.05). CONCLUSION: Within the limitations of this study, it seems
      that drinking Coca-Cola and alcoholic beverages would not be potentially causing
      any problems for the temporary acrylic soft liners.

PMID- 24724143
TI  - Effect of Recycling and Autoclave Sterilization on the Unloading Forces of NiTi
      Closed-Coil Springs: An In Vitro Study.
AB  - STATEMENT OF PROBLEM: Clinicians use the NiTi coil springs frequently for its
      appropriate mechanical properties. PURPOSE: The aim of this study was to
      determine the effect of recycling and autoclave sterilization on the unloading
      forces of NiTi closed coil springs. MATERIALS AND METHOD: Fourteen NiTi closed
      coil spring with the length of 9mm were selected. Each coil was stretched to a
      peak extension of 12 mm. A universal testing machine was used to acquire
      load/deflection curve of the coil springs at 25+/-2 degrees C. The influence of
      thermocycling (1000 cycles,5-55 degrees C), autoclaving (134 degrees C, 32PSI,
      3min) and mechanical strain (9mm extension) which simulated the oral condition,
      were considered. Data were statistically analyzed by adopting Repeated Measures
      MANOVA Paired t-Test. RESULTS: Autoclaving in the 1, 4, 6 steps increased the
      force levels of coil springs about 2-5gf (p< 0.01). Thermocycling reduced their
      force levels about 4-6gf. Prolonged strain at 3, 5 steps decreased the magnitude
      of forces levels about 3-4gf. CONCLUSION: Concerning all the limitations;
      according to the results of this study; it is possible to recycle Ni-Ti closed
      coil springs without significant reduction in their force levels.

PMID- 24724144
TI  - A Comparison between Shear Bond Strength of VMK Master Porcelain with Three Base
      metal Alloys (Ni-cr-T3, VeraBond, Super Cast) and One Noble Alloy (X-33) in Metal
      ceramic Restorations.
AB  - STATEMENT OF PROBLEM: The increase in the use of metal-ceramic restorations and a
      high prevalence of porcelain chipping entails introducing an alloy which is more
      compatible with porcelain and causes a stronger bond between the two. This study
      is to compare shear bond strength of three base-metal alloys and one noble alloy
      with the commonly used VMK Master Porcelain. MATERIALS AND METHOD: Three
      different groups of base-metal alloys (Ni-cr-T3, Super Cast, and VeraBond) and
      one group of noble alloy (X-33) were selected. Each group consisted of 15 alloy
      samples. All groups went through the casting process and change from wax pattern
      into metal disks. The VMK Master Porcelain was then fired on each group. All the
      specimens were put in the UTM; a shear force was loaded until a fracture occurred
      and the fracture force was consequently recorded. The data were analyzed by SPSS
      Version 16 and One-Way ANOVA was run to compare the shear strength between the
      groups. Furthermore, the groups were compared two-by-two by adopting Tukey test.
      RESULTS: The findings of this study revealed shear bond strength of Ni-Cr-T3
      alloy was higher than the three other alloys (94 MPa or 330 N). Super Cast alloy
      had the second greatest shear bond strength (80. 87Mpa or 283.87 N). Both
      VeraBond (69.66 MPa or 245 N) and x-33 alloys (66.53 MPa or 234 N) took the third
      place. CONCLUSION: Ni-Cr-T3 with VMK Master Porcelain has the greatest shear bond
      strength. Therefore, employment of this low-cost alloy is recommended in metal
      ceramic restorations.

PMID- 24724145
TI  - Regional Odontodysplasia: Report of a case.
AB  - Regional odontodysplasia is a rare dental anomaly affecting both primary and
      adult dentitions in the maxilla or mandible or both jaws, whilst involvement of
      the maxilla is more common [1-2]. In most cases, one quadrant is affected. One of
      the characteristics of this anomaly is discolored and soft teeth that can be
      accompanied by swelling or abscess. In this anomaly, enamel and dentin are thin
      and hypoplastic, therefore, the teeth give the impression of "ghost teeth" [2,
      8]. In radiography, the delineation between enamel and dentin is not clear and
      pulp chamber is wide. Histologically, areas of hypocalcified enamel are observed
      and the enamel prisms appear to be irregular in direction [2]. There is a
      disturbance in dentin formation and dentinal tubules are reduced in number. The
      etiology of regional odontodysplasia is still unknown [8]. Managements of these
      cases should be based on the esthetics and functional needs as well as the degree
      of involvement. This report describes a case of regional odontodysplasia in a 3.5
      year old Iranian girl whose chief complaint was the abscess formation in the left
      maxillary primary molar region. This case study aims to report the clinical and
      radiological findings of the current case. 

PMID- 24724146
TI  - Use of low level laser therapy for oral lichen planus: report of two cases.
AB  - Oral Lichen Planus is a chronic inflammatory disease of unknown etiology.
      Erosive/ ulcerative oral lichen planus is often a painful condition that tends to
      become malignant, urging appropriate therapy. Laser therapy has recently been
      suggested as a new treatment option without significant side effects. This
      article presents two cases of erosive/ ulcerative oral lichen planus, who had not
      received any treatment before, treated with 630 nm low level laser. Lesion type
      and pain was recorded before and after treatment. Severity of lesions and pain
      were reduced after treatment. Low Level Laser Therapy was an effective treatment
      with no side effects and it may be considered as an alternative therapy for
      erosive/ulcerative oral lichen planus. 

PMID- 24724147
TI  - Improving medical communication with patients and families: Skills for a complex
      (and multilingual) clinical world.

PMID- 24724148
TI  - Where did all the jobs go?

PMID- 24724149
TI  - Critical care trainees' career goals and needs: A Canadian survey.
AB  - BACKGROUND: For training programs to meet the needs of trainees, an understanding
      of their career goals and expectations is required. OBJECTIVES: Canadian critical
      care medicine (CCM) trainees were surveyed to understand their career goals in
      terms of clinical work, research, teaching, administration and management; and to
      identify their perceptions regarding the support they need to achieve their
      goals. METHODS: The online survey was sent to all trainees registered in a
      Canadian adult or pediatric CCM program. It documented the participants'
      demographics; their career expectations; the perceived barriers and enablers to
      achieve their career goals; and their perceptions relating to their chances of
      developing a career in different areas. RESULTS: A response rate of 85% (66 of
      78) was obtained. The majority expected to work in an academic centre. Only
      approximately one-third (31%) estimated their chances of obtaining a position in
      CCM as >75%. The majority planned to devote 25% to 75% of their time performing
      clinical work and <25% in education, research or administration. The trainees
      perceived that there were limited employment opportunities. Networking and having
      specialized expertise were mentioned as being facilitators for obtaining
      employment. They expressed a need for more protected time, resources and
      mentorship for nonclinical tasks during training. CONCLUSION: CCM trainees
      perceived having only limited support to help them to achieve their career goals
      and anticipate difficulties in obtaining successful employment. They identified
      several gaps that could be addressed by training programs, including more
      mentoring in the areas of research, education and administration.

PMID- 24724151
TI  - Glycan microarrays: new angles and new strategies.
AB  - Carbohydrate microarrays, comprising hundreds to thousands of different glycan
      structures on solid surfaces in a spatially discrete pattern, are sensitive and
      versatile tools for the analysis of glycosylation changes in complex biological
      samples. Glycoarrays are also suitable for monitoring multiple molecular
      interactions with biomolecules where sugars are involved, offering a large
      variety of bioassay options. In this paper we review the most important glycan
      microarray types currently used with their main applications, and discuss some of
      the future challenges the technology faces. 

PMID- 24724150
TI  - Obstructive sleep apnea and driving: A Canadian Thoracic Society and Canadian
      Sleep Society position paper.
AB  - Untreated patients with obstructive sleep apnea (OSA) are at increased risk for
      motor vehicle collisions; however, it is unclear how this should be translated
      into fitness-to-drive recommendations. Accordingly, the Canadian Thoracic Society
      (CTS) Sleep Disordered Breathing Clinical Assembly and the Canadian Sleep Society
      (CSS) assembled a CTS-CSS working group to propose recommendations with regard to
      driving in patients with OSA. Recommendations for assessing fitness to drive in
      noncommercial drivers: 1. Severity of OSA alone is not a reliable predictor of
      collision risk and, therefore, should not be used in isolation to assess fitness
      to drive; 2. The severity of sleep apnea should be considered in the context of
      other factors to assess fitness to drive; 3. The decision to restrict driving is
      ultimately made by the motor vehicle licensing authority; however, they should
      take into account the information and recommendations provided by the sleep
      medicine physician and should follow provincial guidelines; 4. For patients
      prescribed continuous positive airway pressure (CPAP) therapy, objective CPAP
      compliance should be documented. Efficacy should also be documented in terms of
      reversing the symptoms and improvement in sleep apnea based on physiological
      monitoring; 5. For patients treated with surgery or an oral appliance,
      verification of adequate sleep apnea treatment should be obtained; and 6. A
      driver diagnosed with OSA may be recertified as fit to drive based on assessment
      of symptoms and demonstrating compliance with treatment. The assessment should be
      aligned with the provincial driver's license renewal period. Commercial vehicles:
      Assessment of fitness to drive should be more stringent for patients operating
      commercial vehicles. In general, the CTS-CSS working group was in agreement with
      the Medical Expert Panel recommendations to the Federal Motor Carrier Safety
      Administration in the United States; these recommendations were adapted for
      Canadian practitioners.

PMID- 24724152
TI  - Stress in titania nanoparticles: an atomistic study.
AB  - Stress engineering is becoming an increasingly important method for controlling
      electronic, optical, and magnetic properties of nanostructures, although the
      concept of stress is poorly defined at the nanoscale. We outline a procedure for
      computing bulk and surface stress in nanoparticles using atomistic simulation.
      The method is applicable to ionic and non-ionic materials alike and may be
      extended to other nanostructures. We apply it to spherical anatase nanoparticles
      ranging from 2 to 6 nm in diameter and obtain a surface stress of 0.89 N m(-1),
      in agreement with experimental measurements. Based on the extent that stress
      inhomogeneities at the surface are transmitted into the bulk, two characteristic
      length-scales are identified: below 3 nm bulk and surface regions cannot be
      defined and the available analytic theories for stress are not applicable, and
      above about 5 nm the stress becomes well-described by the theoretical Young
      Laplace equation. The effect of a net surface charge on the bulk stress is also
      investigated. It is found that moderate surface charges can induce significant
      bulk stresses, on the order of 100 MPa, in nanoparticles within this size range. 

PMID- 24724153
TI  - Numerical calculations of space charge layer effects in nanocrystalline ceria.
      Part I: comparison with the analytical models and derivation of improved
      analytical solutions.
AB  - Using numerical solutions of the Poisson-equation, one dimensional space charge
      layer (SCL) concentration profiles in CeO2 are calculated. The SCL conductivity
      effects of nanocrystalline CeO2 are analyzed as a function of doping content
      (donor doped, pure and acceptor doped ceria) and SCL potential including not only
      the standard Gouy-Chapman and Mott-Schottky cases, but also the more complex
      mixed situations. The results of the numerical approach are compared with the
      usual analytical approximations. While for the ideal Gouy-Chapman and Mott
      Schottky cases for moderate and high potentials the agreement between analytical
      and numerical solutions is found to be satisfactory, mixed cases and low
      potential situations cannot be reliably treated by using the standard analytical
      approaches. Finally, inspired from the numerical solutions, improved analytical
      equations are proposed which are found to generally yield much more precise
      results and are accurate even for the mixed situations and low potentials. 

PMID- 24724154
TI  - Orientation effects in morphology and electronic properties of anatase TiO(2) one
      dimensional nanostructures. II. Nanotubes.
AB  - In the first part [D. B. Migas et al., Phys. Chem. Chem. Phys., 2014, DOI:
      10.1039/C3CP54988G] by means of ab initio calculations we have analyzed and
      discussed anisotropy effects on electronic properties of <001>-, <100>- and <110>
      oriented anatase TiO2 nanowires. In this part we present results indicating
      crucial changes in morphology of anatase TiO2 nanotubes originating from TiO2
      nanowires by making a hole along the wire axis. The critical wall thickness has
      been found to exist for the nanotubes with <001> and <110> axes: at smaller
      thickness their shape can be rounded, squeezed, viewed as conglomerates of
      nanocrystals and even represented as cylindrical and 'single-walled'-like
      structures formed without rolling up a thin titania layer into a nanotube. In
      general, band dispersion near the gap region of TiO2 nanotubes is close to the
      one of TiO2 nanowires with the same orientation. We have also revealed that
      optimization of the unit cell parameter along the wire axis and consideration of
      quantum confinement and surface state effects are important to provide an
      interpretation of band-gap variation with respect to wall thickness in TiO2
      nanotubes. 

PMID- 24724155
TI  - Orientation effects in morphology and electronic properties of anatase TiO(2) one
      dimensional nanostructures. I. Nanowires.
AB  - By means of ab initio calculations we have revealed the existence of sizable
      anisotropy in electronic properties of anatase TiO2 nanowires with respect to
      orientation: nanowires with <001>, <100> and <110> axes are found to be direct
      band-gap, indirect band-gap and degenerate semiconductor materials, respectively.
      The degenerate semiconducting properties of <110>-oriented TiO2 nanowires are
      predicted to be the intrinsic features closely connected with stoichiometry. A
      band-gap variation with nanowire diameter is also shown to display rather complex
      behavior characterized by a competition between quantum confinement and surface
      state effects that is fully compatible with the available contradictory
      experimental data. Finally, we propose a model to explain the band-gap variation
      with size in TiO2 nanowires, nanocrystals and thin films. 

PMID- 24724156
TI  - High-density biosynthetic fuels: the intersection of heterogeneous catalysis and
      metabolic engineering.
AB  - Biosynthetic valencene, premnaspirodiene, and natural caryophyllene were
      hydrogenated and evaluated as high performance fuels. The parent sesquiterpenes
      were then isomerized to complex mixtures of hydrocarbons with the heterogeneous
      acid catalyst Nafion SAC-13. High density fuels with net heats of combustion
      ranging from 133-141 000 Btu gal(-1), or up to 13% higher than commercial jet
      fuel could be generated by this approach. The products of caryophyllene
      isomerization were primarily tricyclic hydrocarbons which after hydrogenation
      increased the fuel density by 6%. The isomerization of valencene and
      premnaspirodiene also generated a variety of sesquiterpenes, but in both cases
      the dominant product was delta-selinene. Ab initio calculations were conducted to
      determine the total electronic energies for the reactants and products. In all
      cases the results were in excellent agreement with the experimental distribution
      of isomers. The cetane numbers for the sesquiterpane fuels ranged from 20-32 and
      were highly dependent on the isomer distribution. Specific distillation cuts may
      have the potential to act as high density diesel fuels, while use of these
      hydrocarbons as additives to jet fuel will increase the range and/or time of
      flight of aircraft. In addition to the ability to generate high performance
      renewable fuels, the powerful combination of metabolic engineering and
      heterogeneous catalysis will allow for the preparation of a variety of
      sesquiterpenes with potential for pharmaceutical, flavor, and fragrance
      applications. 

PMID- 24724157
TI  - Density-functional description of electrides.
AB  - Electrides are a unique class of ionic solids in which the anions are
      stoichiometrically replaced by electrons localised within the crystal voids.
      There are only nine electrides with known crystal structures and their study
      represents a challenge for theory. A systematic investigation of their electronic
      structure is conducted using semilocal density-functional theory (DFT) in this
      article. The band structure is calculated for each electride and a range of
      techniques including plots of the valence densities, procrystal densities, non
      covalent interaction isosurfaces, and Bader's quantum-chemical topology are
      applied. All of these methods provide consistent results, confirming the presence
      of localised interstitial electrons and demonstrating that these crystals display
      a characteristic electronic structure. 

PMID- 24724158
TI  - Optical absorption and scattering spectroscopies of single nano-objects.
AB  - Developments of optical detection and spectroscopy methods for single nano
      objects are key advances for applications and fundamental understanding of the
      novel properties exhibited by nanosize systems. These methods are reviewed,
      focusing on far-field optical approaches based on light absorption and elastic
      scattering. The principles of the main linear and nonlinear methods are described
      and experimental results are illustrated in the case of metal nanoparticles,
      stressing the key role played by the object environment, such as the presence of
      a substrate, bound surface molecules or other nano-objects. Special attention is
      devoted to quantitative methods and correlation of the measured optical spectra
      of a nano-object with its morphology, characterized either optically or by
      electron microscopy, as this permits precise comparison with theoretical models.
      Application of these methods to optical detection and spectroscopy for single
      semiconductor nanowires and carbon nanotubes is also presented. Extension to
      ultrafast nonlinear extinction or scattering spectroscopies of single nano
      objects is finally discussed in the context of investigation of their nonlinear
      optical response and their electronic, acoustic and thermal properties. 

PMID- 24724159
TI  - [Comprehensive medical care with telemedicine].

PMID- 24724160
TI  - [Wound healing problems after iliac crest operation: appellate decision].

PMID- 24724161
TI  - Software with impact.

PMID- 24724162
TI  - The author file: Erik Meijering.

PMID- 24724163
TI  - Points of significance: Comparing samples-part I.

PMID- 24724164
TI  - What doesn't kill you may reprogram you.

PMID- 24724165
TI  - Response.

PMID- 24724167
TI  - Nanopores sense protein modifications.

PMID- 24724166
TI  - Elusive vibrations.

PMID- 24724168
TI  - Taming the image background beast.

PMID- 24724169
TI  - Capturing promoter-enhancer interactions in high throughput.

PMID- 24724170
TI  - Knocking down Goliath.

PMID- 24724171
TI  - Addendum: Digestion and depletion of abundant proteins improves proteomic
      coverage.

PMID- 24724172
TI  - Response.

PMID- 24724173
TI  - Response.

PMID- 24724174
TI  - Response.

PMID- 24724175
TI  - Response.

PMID- 24724176
TI  - Response.

PMID- 24724177
TI  - Response.

PMID- 24724178
TI  - Response.

PMID- 24724179
TI  - Response.

PMID- 24724180
TI  - [Structured review].

PMID- 24724181
TI  - Phase 3 trials of solanezumab and bapineuzumab for Alzheimer's disease.

PMID- 24724182
TI  - Look back in wonder.

PMID- 24724183
TI  - Political science.

PMID- 24724185
TI  - Climate policy: Streamline IPCC reports.

PMID- 24724184
TI  - Copper rewired.

PMID- 24724186
TI  - Global warming: Improve economic models of climate change.

PMID- 24724187
TI  - [Diagnostic criteria for endoscopic diagnosis of hiatal hernia].

PMID- 24724188
TI  - Response.

PMID- 24724189
TI  - Response.

PMID- 24724190
TI  - Nurse unfairly sacked over anti-racism paper.

PMID- 24724191
TI  - Financial barrier to HIV treatment.

PMID- 24724192
TI  - Nurses eat their own. Bullying and horizontal violence takes its toll.

PMID- 24724193
TI  - Quality use of medicines.

PMID- 24724194
TI  - Carefully does it: tips to prevent injury at work.

PMID- 24724195
TI  - CMS announces delay in two-midnight rule enforcement.

PMID- 24724196
TI  - Checklists come to nursing.

PMID- 24724197
TI  - Pushing the envelope in lines of service.

PMID- 24724198
TI  - I read about infections from the so-called "superbugs."  Is antibiotic resistance
      increasing?

PMID- 24724199
TI  - In regard to the change of the editorial board and the advisory board of the
      Bosnian Journal of Basic Medical Sciences.

PMID- 24724200
TI  - [Modern approaches to antimicrobial and anti-inflammatory photodynamic therapy in
      otorhinolaryngology].
AB  - The objective of the present study was to analyse the currently available methods
      and possibilities for antimicrobial photodynamic therapy (PDT) in medicine with
      special reference to otorhinolaryngology. The results of the treatment of 300
      patients with various suppurative ENT pathologies using antimicrobial PDT were
      subjected to the analysis. It made it possible to elucidate the mechanisms and
      parameters of photodynamic treatment and to reveal disadvantages of the modern
      methods of antimicrobial photodynamic therapy. Special attention is given to the
      management of acute inflammation in the laryngopharynx and to the topical
      problems of up-to-date antimicrobial PDT.

PMID- 24724201
TI  - [Otogenic intracranial disorders: topical problems of diagnostics and treatment].
AB  - The present paper summarized the recently published data on the prevalence,
      etiology, pathogenesis, diagnostics, and treatment of otogenic intracranial
      complications. The results of statistical analysis of the prevalence of otogenic
      intracranial complications are presented in conjunction with the data on their
      structure and the frequency of selected nosological forms. The authors emphasize
      the importance of the problems concerning the choice of the therapeutic strategy
      for the management of otogenic intracranial complications. Special attention is
      given to the peculiarities of antibacterial treatment of various forms of
      otogenic intracranial infection.

PMID- 24724202
TI  - [Spontaneous nasal liquorrhea and the Sternberg canal: scientific hypothesis and
      personal experience].
AB  - Spontaneous nasal liquorrhea (SNL) is a pathological condition previously
      regarded as a casuistic one but increasingly frequently described in the current
      literature. The present review is focused on the causes of SNL, such as the
      anomalous anatomical structure of the nasal cavity and paranasal sinuses. One of
      the variants of the anatomical structure is the so-called Sternberg canal. Its
      anatomical structure and formation in the course of embryonic development are
      described. The presence of the Sternberg canal in the adult subjects is
      considered to be the main cause underlying SNL and meningoencephalocele
      originating from the lateral parts of the sphenoidal sinus. The main variants of
      the endoscopic endonasal approach for the treatment of the fluid fistulas located
      in the lateral parts of the sphenoidal sinuses are described. A series of the
      original authors' observations is reported including 173 patients presenting with
      SN l who were operated in 1999-2011.

PMID- 24724204
TI  - Proceedings of the National Public Health Law Conference, Practical Approaches to
      Critical Challenges, October 10-12, 2012, Atlanta, Georgia.

PMID- 24724203
TI  - [Peculiarities of blood supply of palatal tonsils and the potential risk of
      hemorrhage during tonsillectomy: the literature review and case report].
AB  - The present review encompasses the publications concerning peculiarities of blood
      supply of palatal tonsils, the frequency and variants of the anomalous structure
      of internal carotid artery. Analysis of the literature data has shown that the
      anomalous vascular structure is one of the important risk factors of the
      development of intra- and postoperative hemorrhage, besides redundant blood
      supply of the oropharynx, inflammatory changes in the tissue of tonsils and
      peritonsillar region. Special attention is given to the peculiarities of
      diagnostics of such conditions. The emphasis is laid on the importance of timely
      diagnostics of the anomalous structural changes in the main vessels of the neck
      prior to the surgical intervention on the pharynx. The analysis of the anomalous
      structure of internal carotid artery is presented.

PMID- 24724205
TI  - Proceedings of the 10th International Conference on Wearable Micro and Nano
      Technologies for Personalized Health, June 26-28, 2013, Tallinn, Estonia.

PMID- 24724206
TI  - Evidence appraisal of Kaibori M, Matsui K, Ishizaki M, et al. A prospective
      randomized controlled trial of hemostasis with a bipolar sealer during hepatic
      transection for liver resection. Surgery. 2013;154(5):1046-1052.

PMID- 24724207
TI  - E-cigarettes: still many questions.

PMID- 24724208
TI  - FDA data show arsenic in rice, juice, and beer.

PMID- 24724209
TI  - Find the right pharmacy: our survey of 33,000 readers shows why you may want to
      switch.

PMID- 24724210
TI  - Device can prevent accidental overdoses.

PMID- 24724211
TI  - Big savings with new generic drugs.

PMID- 24724212
TI  - Survive your stay at the hospital: medical errors are linked to 440,000 deaths
      each year.

PMID- 24724213
TI  - Influence of thermal treatment on the stability of phenolic compounds and the
      microbiological quality of sucrose solution following osmotic dehydration of
      highbush blueberry fruits.
AB  - BACKGROUND: Osmotic dehydration is a process of the partial removal of water
      which is based on immersion of material having cellular structure in a hypertonic
      solution. Osmotic dehydration is used as a pretreatment for the dehydration of
      foods before they are subjected to further processing such as freezing, freeze
      drying, vacuum drying. Management of spent syrup is one of the most important
      problems related to osmotic dewatering. Osmotic solutions are heavily polluted
      with of carbohydrates, remains of the dehydrated material and microorganisms. The
      aim of this study was to determine the effect of thermal treatment on the content
      of phenolic compounds and the microbiological quality of sucrose solution used in
      15 cycles of osmotic dehydration of highbush blueberry (Vaccinium corymbosum L.)
      fruits. MATERIAL AND METHODS: The tested material was 65.0 +/-0.5 degrees Brix
      sucrose solution used for 15 cycles of osmotic dehydration of highbush blueberry
      (Vaccinium corymbosum L.). Osmotic dehydration was conducted at 40 degrees C for
      120 min using fruits previously subjected to enzymatic pretreatment. The thermal
      treatment of sucrose solution was conducted at 70, 80, 90, 100 and 115 degrees C
      for 20, 40 and 60 s. The sucrose solution was analysed in terms of total
      polyphenols, particular polyphenols using high performance liquid chromatography
      and microbiological analysis was subjected. RESULTS: Thermal treatment at 70-115
      degrees C for 20 s caused degradation of 8.5% to 12.7% of polyphenols, while as
      much as 23.1% of polyphenols were degraded at 115 degrees C after 60 s. The
      present paper proposes heating parameters that are optimal from the point of view
      of phenolic compound retention and microbiological quality: thermal treatment of
      syrup at 100 degrees C for 40 s. Under these conditions, total polyphenols
      retention was 94.5%, while the retention of individual phenolic compounds varied
      from 89.2% to 37.2%, and that of flavan-3-ols amounted to 89.5%. The studied
      manner of syrup treatment eliminated the problem of syrup contamination with
      yeasts and molds (reducing their levels to less than 1 CFU/mL).

PMID- 24724214
TI  - A systematic approach to the evaluation of acute unexplained crying in infants in
      the emergency department.
AB  - Crying is a common behavior of infancy that can be a signal of a broad spectrum
      of conditions ranging from the normal needs of hunger and sleep to significant
      medical or surgical pathology. In the medical setting, crying is often seen in
      concert with other signifiers of disease or distress, such as fever, vomiting,
      rash, or trauma. However, challenges in evaluation of infants may arise when
      crying is the only sign. A thorough, systematic, and appropriate history and
      physical examination are needed. Additionally, a broad range of medical
      possibilities coupled with caregiver concern need to be considered to ensure
      proper evaluation. In this issue, we will review crying as a chief complaint in
      the emergency department setting and provide a systematic and practical approach
      to the evaluation of crying infants.

PMID- 24724215
TI  - Handoff quality for obstetrical inpatients varies depending on time of day and
      provider type.
AB  - OBJECTIVE: To determine whether obstetric handoff quality differs morning versus
      evening, weekend versus weekday, or based on provider type. STUDY DESIGN: Using
      the American College of Obstetricians and Gynecologists (ACOG) handoff
      guidelines, we developed an observational tool to assess whether handoffs
      included its 8 recommended elements. We observed handoffs between attending
      obstetricians, Obstetrics and Gynecology residents, labor and delivery nurses,
      and certified nurse midwives. Observation times included a balance of morning,
      evening, weekdays, and weekends. Participants were blinded to the study
      objectives. We defined high-quality handoffs as those that included 7 of the 8
      recommended ACOG elements. RESULTS: A total of 425 inpatient handoffs were
      observed: 233 (55%) were morning handoffs and 189 (45%) were evening; 251 (59%)
      were on weekdays and 171 (41%) on weekends. Of the handoffs observed, 201 (48%)
      were presented by residents, 139 (33%) by nurses, 56 (13%) by attending
      obstetricians, and 26 (6%) by midwives. Only 169 (40%) of all handoffs met
      criteria for high quality. A greater percentage of all morning handoffs met
      criteria as compared to evening handoffs (45% vs. 34%, p < 0.05). There was no
      significant difference between the overall percentage of weekday and weekend
      handoffs meeting criteria (39% vs. 42%, p = 0.48). Residents had a higher
      percentage of high-quality handoffs as compared to nurses (55% vs. 32%, p <
      0.001). CONCLUSION: Based on criteria developed for this study, handoff quality
      may vary based on time of day and provider type. These findings present an
      opportunity to further assess reasons for variation and propose changes to
      standardize and improve the handoff process.

PMID- 24724216
TI  - Effect of gonadotropin-releasing hormone antagonist on primordial follicle
      survival in the primate ovary.
AB  - OBJECTIVE: To examine the effects of gonadotropin-releasing hormone (GnRH)
      antagonist on primordial follicle reserve in the primate ovary. STUDY DESIGN: A
      prospective basic research study in which 10 juvenile cynomolgus monkeys (Macaca
      fascicularis) had 1 ovary surgically removed. Six animals were then treated with
      the GnRH antagonist antide (1.0 mg/kg/day) for 14 days, and 4 animals were
      treated with vehicle. After treatment the contralateral ovary was removed and
      both ovaries were prepared for assessment of primordial, primary, and secondary
      follicle numbers. RESULTS: Antide treatment resulted in a modest (13%) but
      significant decrease in primordial follicle number in juvenile macaques (p =
      0.048, n = 6). Three animals demonstrated a marked reduction in primordial
      follicles (19%, 25%, 36%) and 3 animals had no (< 5%) change in primordial
      follicles after antide treatment. Control animals demonstrated no change in
      primordial follicle number following vehicle treatment. Antide had no effect on
      primary, secondary, or early antral follicle numbers and did not affect
      circulating estradiol concentrations. CONCLUSION: In contrast to mice, in which
      GnRH antagonist treatment markedly reduces primordial follicle reserve, the
      effect of antide in nonhuman primates was less dramatic and somewhat variable.
      These data suggest there may be a subset of animals susceptible to the adverse
      effects of GnRH antagonist on primordial follicle survival.

PMID- 24724217
TI  - Abdominal wall endometriosis: a rarely anticipated diagnosis: a 16-year
      experience and brief literature review.
AB  - OBJECTIVE: To evaluate cases of endometriosis of the abdominal wall to determine
      whether the diagnosis was anticipated preoperatively and whether or not the
      patient had undergone prior surgery. STUDY DESIGN: This was a retrospective
      review of records of patients undergoing surgical resection of abdominal wall
      endometriosis from 1996-2011. RESULTS: Nine cases were identified. For the 8
      cases with a recorded preoperative diagnosis, the clinical diagnosis of
      endometriosis was recorded preoperatively in only 25% of cases. The most common
      preoperative diagnosis was neoplasia. CONCLUSION: Abdominal wall endometriosis
      remains a difficult diagnosis to make preoperatively. Awareness among
      gynecologists and consideration of the diagnosis in the differential will
      potentially decrease the number of cases suspected of malignancy and may
      alleviate some stress on the patients' part, due to the possibility of a benign
      diagnosis.

PMID- 24724218
TI  - Combination therapy with paclitaxel, carboplatin and megestrol acetate for the
      management of advanced stage or recurrent carcinoma of the endometrium: a phase
      II study.
AB  - OBJECTIVE: To determine overall survival (OS), progression-free interval (PFI),
      and toxicity in patients with advanced stage or recurrent endometrial cancer
      (EMCA) treated with combination paclitaxel, carboplatin and megestrol acetate.
      STUDY DESIGN: Patients with stage III/IV or recurrent EMCA were enrolled between
      October 2004 and April 2008 and received paclitaxel (175 mg/m2) and carboplatin
      (AUC 6) every 21 days for 6 cycles and megestrol acetate 40 mg orally 4 times
      daily for up to 5 years. Dose reductions were based on grade 3/4 hematologic
      toxicity. Survival was calculated from time of study enrollment. RESULTS: A total
      of 28 patients were evaluable: 21 (75%) patients with stage III/IV disease and 7
      (25%) with recurrent disease. Three patients with recurrence received prior
      radiation. Mean PFI was 40.2 months (29.7-50.6). Mean OS was 50.1 months (41.5
      58.7). After a median 40.4 months (range, 5.6-68.4) of follow-up, 13 patients
      (46%) had no evidence of disease, 4 were alive with disease, and 10 were dead of
      disease. One patient died without evidence of disease. Twenty-three patients
      (82%) completed 6 cycles of chemotherapy. Ten patients experienced a dose
      reduction. Myelosuppression was common, with 22 patients (78%) experiencing grade
      3/4 neutropenia and 6 patients (21%) experiencing grade 3/4 anemia. Three
      patients had a deep vein thrombosis. One patient experienced a pulmonary
      thromboembolus. CONCLUSION: Combination therapy with paclitaxel, carboplatin and
      megestrol acetate demonstrates activity. Myelosuppression is common but can be
      managed with colony-stimulating factors. The addition of hormonal therapy to
      cytotoxic chemotherapy may improve survival.

PMID- 24724219
TI  - Localized provoked vestibulodynia: outcomes after modified vestibulectomy.
AB  - OBJECTIVE: To describe and estimate both short-term and long-term effectiveness
      of a large cohort of women treated with modified vestibulectomy in a single
      surgical service. STUDY DESIGN: A total of 202 patients who were treated with
      modified vestibulectomy for localized provoked vestibulodynia at Mayo Clinic in
      Rochester, Minnesota, were mailed a questionnaire to document severity of vulvar
      pain or discomfort before and after the surgery. RESULTS: In total, 115 patients
      returned the questionnaire. Of the 71 patients who before surgery reported pain
      when inserting a tampon, 52 reported attempting to insert a tampon after surgery.
      Of these 52 patients, 47 (90.4%) noticed moderate to substantial improvement.
      Pain with sexual intercourse occurred in 97.3% (107/ 110) of patients before
      surgery. After surgery, 90 (84.1%) of those 107 patients noted moderate to
      substantial improvement in their pain with intercourse. CONCLUSION: Modified
      vestibulectomy was a successful treatment for patients with localized provoked
      vestibulodynia and resulted in strong patient satisfaction, long-term
      effectiveness, minimal scarring, and few postoperative complications.

PMID- 24724220
TI  - Obstetric laceration repair in the United States: is there a common practice?
AB  - OBJECTIVE: To assess practice preferences in the repair of severe obstetric
      lacerations among obstetrician/gynecologists in the United States. STUDY DESIGN:
      A survey detailing third and fourth degree laceration repair techniques was
      distributed to 634 obstetrician/gynecologists from demographically diverse areas
      of the United States. Categorical outcomes were compared among respondents using
      chi2 or Fisher's exact test where appropriate. RESULTS: Of the 266 respondents,
      there were 124 self-reported "experts" (47%) and 106 physicians-in-training
      (40%). Repair techniques were compared between experts versus nonexperts and
      trainees versus practicing physicians. There were no significant differences
      found between either comparison group on the type and size of suture utilized or
      preferred method of closure for repair. CONCLUSION: There is little variation in
      the practice pattern of complex laceration repairs among obstetrician
      gynecologists in the United States. This commonality should encourage the design
      of standard teaching models and techniques for physicians in training.

PMID- 24724221
TI  - Assessing severity of pain in women with focal provoked vulvodynia: are von Frey
      filaments suitable devices?
AB  - OBJECTIVE: To determine whether von Frey filaments are effective in the
      standardized assessment of the severity of focal provoked vulvodynia (FPV)
      syndrome. STUDY DESIGN: The data of 30 women with FPV attending monthly at our
      vulvovaginal disease clinic, for a collective total of 141 visits over 6 months,
      were analyzed. At each visit sensitivity tests at the vulvar vestibule were
      performed at the 5 and 7 o'clock area, totaling 282 measurements. A
      questionnaire, blinded to the examining physician, and a visual analogue score
      (VAS) of pain ranging from 1 (no pain) to 10 (maximal pain) was obtained of the
      discomfort felt when attempting sexual intercourse. RESULTS: The VAS, the
      investigator assessment of redness, and the 1 to 10 score result of the cotton
      swab touch test at 5 and 7 o'clock were superior diagnostic tools for assessing
      the severity of the pain when compared to the use of von Frey filaments.
      CONCLUSION: Although elegant because of the promise of objective,
      semiquantitative measurements, von Frey filaments are less suitable devices to
      assess severity of disease and response to treatment than are cotton swab 1 to 10
      pain scores and clinical parameters like subjective pain (VAS) and objective
      focal redness.

PMID- 24724222
TI  - Perceived healthcare providers' responsibility with postpartum depression: whose
      problem is it, anyway?
AB  - OBJECTIVE: To explore public perceptions of healthcare providers'
      responsibilities in recognizing, screening, discussing, and making referrals for
      postpartum depression (PPD). STUDY DESIGN: A total of 87 college students
      completed a questionnaire asking various questions related to perceptions of
      healthcare providers and PPD. RESULTS: Participants perceived physicians and
      obstetricians/gynecologists as having more responsibility for recognizing and
      screening for PPD as compared to pediatricians and nurses. Participants also
      believed that physicians are deemed as most responsible for discussing symptoms
      of PPD and for making mental health referrals for PPD as compared to OB/GYNs,
      pediatricians, and nurses. CONCLUSION: Public perceptions of healthcare
      providers' responsibilities with PPD offer additional information helpful for the
      efforts in identifying and treating PPD. Understanding which healthcare provider
      patients may look to for assistance with PPD allows practitioners to consolidate
      resources and play a more active role in working with PPD.

PMID- 24724223
TI  - Worldwide survey of the results of treating gestational trophoblastic disease.
AB  - OBJECTIVE: To determine factors influencing outcome for patients with gestational
      trophoblastic disease (GTD) from throughout the world. STUDY DESIGN: Physicians
      known to treat GTD were sent a questionnaire. RESULTS: There were 32 responses
      from 17 countries, totaling 26,153 patients. Of 14,093 patients with complete
      mole 20.6% developed trophoblastic neoplasia, and 5.7% died. There were 10,230
      patients with partial mole, of whom 6.5% received therapy for neoplasia. There
      were 548 patients with post-term pregnancy choriocarcinoma, of whom 13.4% died.
      Of 137 patients with placental site trophoblastic tumor 16.1% died. The remaining
      1,165 patients did not fit into a designated diagnostic category. The mortality
      rate for 2,818 patients with GTD primarily treated at a trophoblast center was
      2.1%, as compared with 8% among 1,854 patients referred after failure of primary
      treatment (p < 0.01). CONCLUSION: Patients treated by physicians experienced in
      the management of trophoblastic disease have better results and survival.

PMID- 24724224
TI  - Value of amniotic fluid IL-8 and Annexin A2 in prediction of preterm delivery in
      preterm labor and preterm premature rupture of membranes.
AB  - OBJECTIVE: To investigate the clinical significance and value in the prediction
      of preterm delivery of combined amniotic fluid IL-8 and Annexin A2 levels in
      preterm premature rupture of membranes (PPROM) and preterm labor (PTL). STUDY
      DESIGN: Sixty pregnant women at < 32 gestational weeks who developed PTL were
      divided into a PPROM group and a non-PPROM group. Ten normal pregnant women
      served as a control group. IL-8 and Annexin A2 levels were measured in amniotic
      fluid samples from each patient. RESULTS: Amniotic fluid IL-8 and Annexin-A2
      levels in PTL (PPROM and non-PPROM groups) were significantly higher than those
      of the controls (p < 0.05). The PPROM group displayed higher amniotic fluid
      Annexin-A2 levels than did the non-PPROM group, with a statistically significant
      difference (p < 0.05). The PPROM group showed higher amniotic fluid IL-8 levels
      than did the non-PPROM group; however, this was statistically insignificant (p =
      0.56). Combined detection of amniotic fluid IL-8 and Annexin-A2 in the prediction
      of preterm delivery within 2 weeks of measurement showed sensitivity of 81.25%,
      specificity of 88.89% and PPV of 92.86%. CONCLUSION: Amniotic fluid IL-8 and
      Annexin-A2 levels are associated with the occurrence of PPROM and PTL. Combined
      detection of IL-8 and Annexin-A2 levels in identifying preterm delivery within 2
      weeks in PTL and PPROM is of possible clinical and predictive value.

PMID- 24724225
TI  - Serum beta human chorionic gonadotropin levels on day 12 after in vitro
      fertilization in predicting final type of clinical pregnancy.
AB  - OBJECTIVE: To optimize the cutoff level for serum beta human chorionic
      gonadotropin (beta-hCG) determination on day 12 after embryo transfer (ET). STUDY
      DESIGN: This was a retrospective data analysis. RESULTS: beta-hCG values on day
      12 after ET of 1,057 clinical pregnancies undergoing in vitro fertilization were
      analyzed. Receiver operating characteristic curves and optimal cutoff values to
      discriminate between singleton and multiple pregnancies, intrauterine pregnancy
      and ectopic pregnancy, and live-birth pregnancy and miscarriage were calculated
      separately. Cutoff values were found at 239 IU/L for multiple pregnancies
      (sensitivity 69.0%, specificity 74.5%, positive predictive value [PPV] 48.4%,
      negative predictive value [NPV] 86.1%), 91 IU/L for ectopic pregnancy
      (sensitivity 82.7%, specificity 71.1%, PPV 15.5%, NPV 98.5%), and 143 IU/L for
      miscarriage (sensitivity 72.3%, specificity 63.0%, PPV 33.1%, NPV 90.0%),
      respectively. CONCLUSION: beta-hCG cutoff values on day 12 after ET determined by
      a ROC curve analysis are useful to predict the final type of clinical pregnancy.

PMID- 24724226
TI  - Postpartum uterine response to oxytocin and carbetocin.
AB  - OBJECTIVE: To obtain quantitative data on uterine contractility postpartum and
      compare the response of intramuscular oxytocin to carbetocin. STUDY DESIGN: A
      prospective study using an intrauterine pressure transducer (IUPT) to measure
      frequency, amplitude, and duration of contractions following the administration
      of either oxytocin (10 U) or carbetocin (30 microg). RESULTS: The IUPT was
      tolerated by all subjects and generated useful data 90% of the time in most
      subjects (12/16). Both drugs generated hypertonic uterine activity with
      contractions of similar duration. However, carbetocin resulted in contractions of
      sustained higher amplitude and frequency and therefore higher uterine performance
      as expressed by Montevideo units. This uterotonic effect of carbetocin lasted for
      3 hours. CONCLUSION: IUPT monitoring generated quantitative data on postpartum
      uterine activity. When compared to high-dose oxytocin, a low dose of carbetocin
      has a more prolonged effect on uterine activity both in terms of a higher
      amplitude and frequency of contractions.

PMID- 24724227
TI  - An unusual-appearing suburethral diverticulum resulting from trauma: a case
      report.
AB  - BACKGROUND: A suburethral diverticulum is a herniation of the urethra into the
      potential space between the anterior vaginal wall and the periurethral fascia. We
      report a case of an unusual-appearing suburethral diverticulum that resulted from
      repetitive self-induced trauma. CASE: A 43-year-old, mentally handicapped woman
      presented to our clinic for evaluation of a papillary mass projecting from her
      anterior vaginal wall. Her caretakers reported that the woman traumatized herself
      periodically to induce vaginal bleeding. After evaluation the mass was excised in
      the operating room, and the diagnosis of a suburethral diverticulum was
      confirmed. CONCLUSION: Self-induced trauma as an etiology of suburethral
      diverticula should be considered in patients with atypical-appearing masses of
      the anterior vaginal wall.

PMID- 24724228
TI  - Endometrial adenocarcinoma arising in a Turner's syndrome patient with
      spontaneous menstruation: a case report.
AB  - BACKGROUND: Women with Turner's syndrome exhibit anovulation, and the majority do
      not spontaneously menstruate. We present an unusual case of endometrial
      adenocarcinoma developing in a Turner's syndrome patient who was exhibiting
      spontaneous menstruation while not receiving regular hormone therapy. CASE: The
      patient's karyotype from blood lymphocytes was a mosaic of 45,XO/ 46,XX. Menarche
      and sexual development were normal. Her menstrual cycle had been regular for one
      year, but then became noticeably irregular. At age 26 she was referred to our
      hospital after bleeding for almost 1 year. An endometrial adenocarcinoma was
      detected during performance of diagnostic endometrial curettage. A total
      abdominal hysterectomy with bilateral salpingo-oophorectomy and pelvic
      lymphadenectomy was conducted. The final histological diagnosis was endometrial
      adenocarcinoma, Grade 1, pT1a N0 M0. Fluorescence in situ hybridization analysis
      of the right and left ovaries revealed a mosaic karyotype of 45,XO/ CONCLUSION:
      Previous reports regarding Turner's syndrome detected spontaneous menstruation in
      only 16% of patients; however, spontaneous menstruation was observed in 8 of 10
      (80%) Turner's syndrome cases that developed endometrial carcinoma without
      receiving regular hormone therapy (p < 0.0001). Hormone therapy may be indicated
      for an irregular menstrual cycle in Turner's syndrome patients.

PMID- 24724229
TI  - Pulmonary artery dissection leading to cardiac tamponade as a cause of maternal
      death in a woman with pulmonary hypertension: a case report.
AB  - BACKGROUND: Severe pulmonary hypertension in pregnancy is known to carry a 40%
      risk of death for the mother. The most common cause of death in cases of
      pulmonary hypertension is heart failure. CASE: We present a case of maternal
      death due to dissection of the pulmonary artery resulting in cardiac tamponade.
      CONCLUSION: The sudden onset of severe chest pain radiating to the back should
      alert the clinician to the possibility of pulmonary artery dissection in pregnant
      patients with pulmonary hypertension. Severe chest pain may not be accompanied by
      changes in vital signs or oxygen saturation. Immediate delivery should be
      considered. However, delivery may worsen the mother's condition due to postpartum
      cardiovascular changes.

PMID- 24724230
TI  - Epidemiological and histopathological study of leprosy cases in the state of
      Sergipe, Brazil.
AB  - Leprosy is a disease with different ratings due to the diversity of clinical
      manifestations. The most used classification by Reference Centers is the
      histopathological, which has been considered to have better specificity and
      sensitivity. Thus, the aim of this study was to determine the histopathological
      types of profile of Leprosy patients from different parts of Sergipe, Brazil,
      from 1985 to 2005. For this purpose, it was used histopathological diagnosis
      reports filed at Prof. Dr. Nestor Piva Memorial from 1985 to 2005. There were
      2,102 reports with Leprosy diagnosis, from which 1,165 (55.4%) cases were women,
      1,224 (58.2%) cases were of mixed race and 1,835 (87.3%) were from the
      metropolitan area of Aracaju/SE. The mean age was 36.62 year. The smear
      microscopy classified 1,669 (79.4%) lesions as paucibacillary and there was a
      predominance of tuberculoid and indeterminate forms. Men were more likely to be
      multibacillary, as well as being the lepromatous pole. The determination of
      histopathological forms and the knowledge about the association and the
      epidemiological profile are important tools to contribute to public health
      policies.

PMID- 24724231
TI  - Trend in decline in leprosy disabilities of a LEPRA project in Malkangiri
      district, Odisha, India.
AB  - This a retrospective analysis of the changes in 646 disabilities occurred amongst
      3979 cases registered during 19 years from 1992 to 2010 in Malkangiri district.
      This amounted to 16.2% of cases with disability segregated to 310 (48%) Grade 1
      and 336 (52%) Grade 2. In this project, managed by LEPRA India, POD care was in
      practice from the year 1992 and records were updated regularly. An analysis of
      the annual records showed that the next year-end balance increased up to the year
      2001 followed by gradual decline. Within this period the total cases with
      disabilities declined by about 369 (57%) due to death by aging 204 (55%),
      migration from the area 77 (21%) and reversing to normal 88 (24%) in cases.
      Deletion due to recovery to normal especially with sensory impairment is fairly
      good with or without steroid. Disability percentage in new cases declined
      steadily especially Grade 2 from 30% to 1%, initial high rate attributed mostly
      to backlog cases. In later years the rate is erratic high amongst low number of
      new cases. Absolute number indicates the situation better. Such study helps to
      roughly extrapolate the existing disability load in a particular area and assists
      in planning for care and prevention.

PMID- 24724232
TI  - Evaluation of the diagnostic value of immunocytochemistry and in situ
      hybridization in the pediatric leprosy.
AB  - Leprosy is characterized by a long and variable incubation period and a chronic
      clinical course. Diagnosis of leprosy is essentially based on clinical features.
      Although the majority of cases can be diagnosed clinically yet alternative
      methods for diagnosis are required especially for early cases.
      Immunocytochemistry and in situ hybridization can be a valuable tool for
      diagnosis for early cases. The present study is aimed to assess the diagnostic
      value of immunocytochemistry and in situ hybridization in cytological specimens
      and to compare these techniques with Z.N. staining. This prospective study was
      carried out in 26 patients below 18 years of age of leprosy. Clinical examination
      of each patient was done and categorized according to IAL. After taking consent,
      three skin smears was taken, one for Z.N. staining and remaining two for
      immunocytochemistry and in situ hybridization respectively. Routine skin smear
      examination by Z.N. staining method confirmed the diagnosis in 4/26 (15.83%) and
      these belonged to BB, BL category. Immunocytochemistry showed positivity in 10/15
      (66.6%) in BT and 72.7% in BB/BL leprosy. Immunocytochemistry improved the
      diagnosis by 53.85%, and the results were statistically significant (p < 0.01).
      In situ hybridization showed the positive results in 80% cases of BT leprosy and
      90.9% cases of BB/BL leprosy. In situ hybridization improved the diagnosis by 70%
      in comparison to ZN staining and the results were statistically significant (p <
      0.01). This study supports that immunocytochemistry and in situ hybridization
      enhance the diagnosis of leprosy when compared to routine skin smears stained by
      Z.N staining. They are important diagnostictoolsfor definitive diagnosis in early
      as well as established cases of leprosy.

PMID- 24724233
TI  - Reconstruction of moderately depressed nose in leprosy (a long-term follow-up).
AB  - Fifty seven leprosy patients having moderately collapsed nose were taken for
      nasal reconstruction. The bone graft was obtained from the second metatarsal of
      the foot. It was corticoperiosteal and placed in between lining and the nasal
      skin. 48 patients were reviewed periodically at 3 months, initially for 2 years
      and irregular visits at 3 to 5 year intervals in last 25 years. The nasal
      architecture and donor site problems were evaluated. 26 patients were completely
      satisfied, 14 patients were happy with shape of the nose along with some other
      problems. 6 cases showed the poor results. Two cases developed the deformity
      after seven years of correction. The details of the technique and the problems
      occurring during and long-term follow up have been discussed.

PMID- 24724234
TI  - Knowledge and attitude about leprosy in Delhi in post elimination phase.
AB  - Leprosy is a chronic communicable disease since age associated with stigma and
      suffering. India claims its elimination but in some districts it remains a public
      health problem. A cross sectional study was conducted and a total of 60 persons
      were interviewed with an objective to assess the knowledge and attitude about
      leprosy among sample of 30 adults each from leprosy colony dwellers and urban
      slum dwellers in South District of Delhi. RESULT: Knowledge about the leprosy
      among leprosy colony dwellers was significantly lower than the slum dwellers.
      Both the groups still believed that leprosy could be due to curse of God, past
      misdeeds, and could spontaneously occur. Respondents of leprosy colony had
      significantly less adverse attitude such as leprosy patient should never get
      married (12% vs 57%), patient should be kept in leprosy colony (0 vs 30%) and
      should not be allowed to enter religious places (0 vs 23%). Surprisingly 73% of
      them had not heard about MDT and only (68%) knew that treatment is available free
      of cost in all Govt. hospitals. Only about half of the respondents knew that
      deformities could be corrected. CONCLUSION: This study reflects the poor
      awareness and negative attitudes towards leprosy particularly among leprosy
      patients themselves, which could be one of the reasons for slow progress in
      Leprosy Elimination Program in Delhi.

PMID- 24724235
TI  - Big-picture thinkers.

PMID- 24724237
TI  - D.O. training update.

PMID- 24724236
TI  - Another prediction.

PMID- 24724238
TI  - Crash course.

PMID- 24724239
TI  - Gut instinct.

PMID- 24724240
TI  - Plumbers, pipefitters and preventive medicine.

PMID- 24724241
TI  - Public-minded.

PMID- 24724242
TI  - Do as I say?

PMID- 24724243
TI  - Promise or peril?

PMID- 24724244
TI  - Advocating for the greater good: how the MMA is diving into public health issues.

PMID- 24724245
TI  - Coordinating care.

PMID- 24724246
TI  - Linking primary care and public health in Minnesota.

PMID- 24724247
TI  - The high cost of bath salts: a study of the health care burden of illicit
      synthetic drug use in Duluth, Minnesota.
AB  - The Minnesota Department of Health conducted an exploratory epidemiologic
      investigation into the health care burden of illicit synthetic drug (ISD) use in
      Duluth, Minnesota. Staff reviewed medical records of 78 patients with suspected
      ISD use who were treated in emergency departments at two Duluth-area hospitals
      from January through September 2013. Most (67%) were unemployed, 75% arrived at
      the hospital by ambulance or police escort and 57% were admitted to the hospital.
      Use of ISDs has the potential to create a significant burden on the health care
      system and public services. Therefore, effective prevention and response
      strategies need to be developed.

PMID- 24724248
TI  - Making the C.A.S.E. for the human papillomavirus vaccine: how to talk to parents
      and adolescents.
AB  - Human papillomavirus (HPV) vaccination rates have been stagnant or falling for
      females, and vaccination efforts are off to a poor start for males. Despite
      recommendations by the Centers for Disease Control and Prevention's Advisory
      Committee on Immunization Practices and other authorities that all adolescents
      receive the vaccine at 11 to 12 years of age, the latest data indicate no more
      than 32% of females ages 13 to 17 years have completed all three doses; the rate
      for males is less than 8%. Most parents are unfamiliar with HPV and are unaware
      that their children may one day become infected. In addition, they may not know
      that the vaccine is recommended. Others may question its safety and whether their
      child needs it; or they may think their child is too young to be vaccinated.
      Whether adolescents get the vaccine depends largely on their clinician: A
      clinician who directs a parent to have their child vaccinated will be more
      successful in ensuring that child is vaccinated than those who merely tell
      parents the vaccine is available. The Minnesota Chapter of the American Academy
      of Pediatrics teaches clinicians to address vaccine hesitancy among parents using
      the C.A.S.E. approach. This approach is not just for parents; it also can be used
      to address adolescents' concerns in a persuasive manner.

PMID- 24724249
TI  - Physical activity, fruit and vegetable intake, and smoking in working-aged
      adults: opportunities for prevention in primary care.
AB  - The purpose of this study was to document health behaviors (diet, physical
      activity, cigarette smoking) in working-aged adults with identified primary care
      providers. We surveyed 1,344 adults in Minnesota and North Dakota 25 to 64 years
      of age from Essentia Health primary care patient lists in May of 2012. A 21-page,
      self-administered questionnaire asking about their health habits was mailed to
      the sample three times during a three-month period. The response to the three
      mailings was 38.8%, with a final sample size of 522 completed surveys. Overall,
      18.5% (95% CL = 18.2, 18.8) of men and 22.3% (95% CL = 22.0, 22.6) of women
      reported currently smoking. The BMI distribution (normal, overweight and obese)
      was 16.9%, 40.0% and 43.1%, respectively, for men and 32.8%, 31.7% and 35.5%,
      respectively, for women. Mean fruit and vegetable intake was significantly lower
      for men than women (mean = 1.92 servings a day for men and 2.15 for women).
      Physical inactivity was reported by 6.2% (95% CL = 6.0, 6.4) of the men and 7.2%
      (95% CL = 7.0, 7.4) of the women. After adjusting for the other variables, people
      in the older age groups were less likely to smoke (OR = 0.78, 95% CL = 0.65,
      0.93) than those in the younger age groups, people living in rural areas were
      more likely to be obese (OR = 1.67, 95% CL = 1.16, 2.39) than those living in
      urban areas, and women were more likely than men to be inactive or have low
      levels of physical activity (OR = 1.47, 95% CL = 1.02, 2.11). These data
      highlight a number of modifiable risk factors for chronic diseases that primary
      care providers could address in order to improve long-term health outcomes.

PMID- 24724251
TI  - Providers, payers get appy.

PMID- 24724250
TI  - A surprising encounter.

PMID- 24724252
TI  - Accidental informaticist.

PMID- 24724253
TI  - [7 myths about the allergy topic].

PMID- 24724254
TI  - [Latest fees reform of the KBV. Nothing commendable in the family practitioner
      EBM].

PMID- 24724255
TI  - [Health policy in coalition agreement. Good effort - but not a great success].

PMID- 24724256
TI  - [Borderline vitamin B 12 level. Is it clinically relevant?].

PMID- 24724257
TI  - [Astronauts, extreme athletes, disaster relief workers. What drives the adventure
      seeking physicians?].

PMID- 24724258
TI  - [TOPCAT study. Heart failure: spironolactone disappoints in the "problem
      patient"].

PMID- 24724259
TI  - [Extra quick training for diabetic patients. Electrostimulation of the quadriceps
      muscle improves insulin sensitivity].

PMID- 24724260
TI  - [Hematochezia during anticoagulation. Pulmonary embolism as a life saver?].

PMID- 24724261
TI  - [Multimorbidity, long-standing type 2 diabetics. HbA1c to 6.5% - must it be?].

PMID- 24724262
TI  - [Answer by Dr. Hulda Rieder].

PMID- 24724263
TI  - [Common colds. Good prescriptions from empirical medicine].

PMID- 24724264
TI  - [Senior citizens becoming increasingly more travel adventurous. Well prepared
      into the wide world].

PMID- 24724265
TI  - [Is BSE only sleeping?].

PMID- 24724266
TI  - [Renal denervation in hypertension: The effect persists].

PMID- 24724267
TI  - [Scrotal calcinosis].

PMID- 24724268
TI  - [The best surgery day is Monday].

PMID- 24724269
TI  - [ADHD: Methylphenidate for epileptics?].

PMID- 24724270
TI  - [Implant on the move].

PMID- 24724271
TI  - [Management of testicular cancer].

PMID- 24724272
TI  - [Short PQ Intervall. Preexcitation syndrome].

PMID- 24724273
TI  - [Hypertension new guidelines--new strategies?].

PMID- 24724274
TI  - [Surprising increase of creatinine].

PMID- 24724275
TI  - [New ultrasound and molecular aspects of thyroid nodule diagnostics].

PMID- 24724276
TI  - [Myth about causes and treatment of constipation].

PMID- 24724277
TI  - [Treatment options in popliteal aneurysm repair].

PMID- 24724279
TI  - A new species of Simulium (Gomphostilbia) (Diptera: Simuliidae) from Thailand,
      with keys to 11 species of the Simulium varicorne species-group.
AB  - Simulium (Gomphostilbia) piroonae sp. nov. is described on the basis of females,
      males, pupae, and mature larvae collected in Mae Hong Son Province, Thailand.
      This new species is placed in the chumpornense subgroup of the varicorne species
      group in the subgenus Gomphostilbia by having the antenna with eight
      flagellomeres, the pleural membrane bare, the female subcosta lacking hairs, and
      the pupal gill basally divided into two somewhat inflated branches. It is
      distinguished from all 10 known species of this group by the pupal gill with six
      filaments. Keys to identify 11 species of the varicorne species-group are
      provided for females, males, pupae, and mature larvae.

PMID- 24724280
TI  - Mites of the genus Trichorhynchiella (Acariformes: Harpirhynchidae): A new
      example of ovoviviparity in acariform mites.
AB  - The small genus Trichorhynchiella Fain, 1995, including two species of permanent
      bird ectoparasites belonging to the family Harpirhynchidae (Acariformes:
      Cheyletoidea), is revised. The generic diagnosis is emended. The type species,
      Trichorhynchiella paddae Fain, 1995 from Lonchura oryzivora (L, 1758)
      (Passeriformes: Estrildidae) from Southeast Asia and Trichorhynchiella
      phleocryptes sp. n. from Phleocryptes melanops (Viellot, 1817) (Passeriformes:
      Furnariidae) from Argentina are redescribed and described, respectively. The
      phenomenon of ovoviviparity inherent to females of this genus is briefly
      discussed. In almost immobile physogastric females of Trichorhynchiella,
      ovoviviparity eliminates necessity to attach eggs to the host body.

PMID- 24724278
TI  - Can Horton hear the whos? The importance of scale in mosquito-borne disease.
AB  - The epidemiology of vector-borne pathogens is determined by mechanisms and
      interactions at different scales of biological organization, from individual
      level cellular processes to community interactions between species and with the
      environment. Most research, however, focuses on one scale or level with little
      integration between scales or levels within scales. Understanding the
      interactions between levels and how they influence our perception of vector-borne
      pathogens is critical. Here two examples of biological scales (pathogen
      transmission and mosquito mortality) are presented to illustrate some of the
      issues of scale and to explore how processes on different levels may interact to
      influence mosquito-borne pathogen transmission cycles. Individual variation in
      survival, vector competence, and other traits affect population abundance,
      transmission potential, and community structure. Community structure affects
      interactions between individuals such as competition and predation, and thus
      influences the individual-level dynamics and transmission potential. Modeling is
      a valuable tool to assess interactions between scales and how processes at
      different levels can affect transmission dynamics. We expand an existing model to
      illustrate the types of studies needed, showing that individual-level variation
      in viral dose acquired or needed for infection can influence the number of
      infectious vectors. It is critical that interactions within and among biological
      scales and levels of biological organization are understood for greater
      understanding of pathogen transmission with the ultimate goal of improving
      control of vector-borne pathogens.

PMID- 24724281
TI  - Assessment of the taxonomic status of some species included in the shannoni
      complex, with the description of a new species of Psathyromyia (Diptera:
      Psychodidae: Phlebotominae).
AB  - The Shannoni complex, comprising sand flies belonging to the subgenus
      Psathyromyia (Psathyromyia) Barretto, consists of several species, of which the
      females have banana-shaped spermathecae and the males have digitiform parameres
      on the terminalia. Among these species, Psathyromyia shannoni (Dyar) and two taxa
      considered as its junior synonyms (Phlebotomus limai Fonseca and Phlebotomus
      bigeniculatus Floch & Abonnenc), Psathyromyia pestanai (Barretto & Coutinho), and
      a new species are the focus of this study. On the basis of morphological and
      morphometric characters, Psathyromyia bigeniculata (Floch and Abonnenc) stat.
      rev.; comb. n. and Psathyromyia limai (Fonseca) stat. rev.; comb. n. are
      resurrected from the synonymy of Pa. shannoni. Pa. pestanai is proposed as a new
      junior synonym of Pa. limai. Psathyromyia ribeirensis sp. n., occurring in the
      middle and upper Ribeira Valley in the state of Sao Paulo, Brazil is described.
      Pa. limai, described from the Serra da Cantareira (Sao Paulo municipality) and
      also found in the lower Ribeira Valley and on the adjacent coastal plain, is
      morphologically very close to the new species.

PMID- 24724283
TI  - Occurrence and county-level distribution of ticks (Acari: Ixodoidea) in Nebraska
      using passive surveillance.
AB  - A 100 yr (1911-2011) examination of tick submissions was compiled from the U.S.
      National Tick Collection and three state databases to determine tick species
      occurrence in Nebraska Sixteen tick species were identified including Amblyomma
      americanum (L.), Dermacentor variabilis (Say), Dermacentor albipictus (Packard),
      Dermacentor andersoni Stiles, Haemaphysalis leporispalustris (Packard),
      Rhipicephalus sanguineus (Latreille), and Otobius megrini (Dughs). Amblyomma
      maculatum Koch and Ixodes scapularis Say were identified in only two and four
      submissions, respectively, but all identifications have occurred after 1990.
      County submissions were associated with county population, forested area, and
      number of recreation areas.

PMID- 24724282
TI  - Spatial distribution of counties in the continental United States with records of
      occurrence of Amblyomma americanum (Ixodida: Ixodidae).
AB  - In addition to being a major nuisance biter, the lone star tick, Amblyomma
      americanum (L.), is increasingly recognized as an important vector of pathogens
      affecting humans, domestic animals, and wildlife. Despite its notoriety, efforts
      have been lacking to define the spatial occurrence ofA. americanum in the
      continental United States with precision beyond that conveyed in continental
      scale distribution maps. Here we present a county-level distribution map for A.
      americanum generated by compiling collection records obtained from a search of
      the published literature and databases managed by the USDA, U.S. National Tick
      Collection, and Walter Reed Biosystematics Unit. Our decadal and cumulative maps,
      which visually summarize 18,121 collections made between 1898 and 2012, show that
      A. americanum is either established (> or = six ticks or -two life stages) or
      reported (<six ticks of a single life stage or number of ticks not specified) in
      1,300 counties distributed among 39 states and the District of Columbia. Our
      cumulative map depicts a species with a core distributional area in the southern
      part of the eastern United States, but that also occurs further north, especially
      along the Atlantic Coast and into the Midwest. Although our decadal maps suggest
      a northward shift in the tick's distribution in recent decades, the lack of
      systematic tick surveillance makes this difficult to confirm. The data presented
      herein should aid in identifying areas posing risk for A. americanum-associated
      illnesses and environmental correlates that define the tick's distributional
      limits.

PMID- 24724284
TI  - Cryopreservation of embryos of Lucilia sericata (Diptera: Calliphoridae).
AB  - Embryos of Lucilia (Phaenicia) sericata (Meigen) (Diptera Calliphoridae), the
      green blowfly, were successfully cryopreserved by vitrification in liquid
      nitrogen and stored for 8 yr. Embryos incubated at 19 degrees C for 17 h after
      oviposition were found to be the most appropriate stage to cryopreserve. Removal
      of the embryonic surface water was done using 2-propanol before the alkane
      treatment to permeabilize the embryo. Exposure to 2-propanol for > 10 s caused
      necrotic tissue damage in the embryos. Among the alkanes used, hexane was found
      to be a superior permeabilizing solvent compared with heptane or octane, with
      embryo hatching rates on par with the controls. Treatment with the vitrification
      solution for < 12 min was insufficient to vitrify the embryos. Treatment time in
      the solution beyond 15 min reduced embryo viability. However, the percentage of
      embryos vitrifying upon exposure to liquid nitrogen vapor remained constant after
      12 min of treatment. Long-term storage was initiated in 2004, and the mean hatch
      percentage recorded then for the short-term cryopreserved embryos was 9.51%. When
      the long-term stored samples were retrieved in 2012, 8.47% of the embryos
      hatched, 66.36% larvae pupariated, and 36.96% of the pupae eclosed. Recent
      optimization of the technique has resulted in a hatch rate of 34.08 +/- 15.5%, of
      which 67.5% of the larvae pupariated and 72% of the pupae eclosed to normal
      flies.

PMID- 24724285
TI  - Mosquito larvae change their feeding behavior in response to kairomones from some
      predators.
AB  - The efficacy of using predators for the biological control of mosquito disease
      vectors will be reduced if mosquito larvae respond to predator presence. The
      larvae of two mosquito species were investigated to study whether they responded
      to predator kairomones by increasing surface filter-feeding, which is a less
      active and thus less risky feeding strategy than bottom feeding. Culex
      quinquefasciatus Say is normally found in highly polluted water, where it will
      have little contact with predators. Except for some third instars, its larvae
      showed no response to four different types of predators. Culiseta longiareolata
      Macquart, living in rain-filled rock pools, is frequently attacked by a range of
      predators. All instars tested (second, third, and fourth instars) strongly
      responded to chemicals from dragonfly nymphs (Crocothemis erythraea Brulle),
      damselfly nymphs (Ischnura evansi Morton), and the fish Aphanius dispar Ruppel.
      However, they did not respond to final-instar water scorpions (Nepa cinerea L.),
      which would not feed on the mosquito larvae. Second- and third-instar Cs.
      longiareolata produced the same response to chopped up mosquito larvae as they
      did to dragonfly nymphs, but fourth instars produced a significantly stronger
      response to dragonfly nymphs-both those unfed and those fed in situ. Thus, Cs.
      longiareolata not only identified different predators and responded accordingly,
      but also responded to conspecific alarm pheromones. Cx quinquefasciatus showed
      little response to predators or to alarm pheromones from damaged conspecific
      larvae.

PMID- 24724286
TI  - Behavioral differences among four co-occurring species of container mosquito
      larvae: effects of depth and resource environments.
AB  - Mosquito larvae often exhibit different behaviors depending on the aspects of the
      aquatic environment, including the presence of different physical factors and
      detrital food sources. Regardless of these physical differences, different genera
      also devote different amounts of time to different behaviors. To determine if
      differences existed among four focal mosquito species (Aedes albopictus (Singh),
      Aedes triseriatus (Say), Culex quinquefasciatus (Say), Culex coronator Dyar &
      Knab), we recorded behaviors under different food environments (animal detritus,
      leaf detritus, and inoculum + inert material) and depths (shallow and deep).
      Based on past work, we predicted that larval mosquitoes in the genus Culex would
      spend more time filtering or resting at the surface of containers, whereas Aedes
      mosquitoes would spend more time browsing on surfaces. Behaviors were recorded
      for 30 min and were used to generate instantaneous scan census of behavior
      (thrashing, browsing, and resting or filtering) and locations (top, middle,
      bottom, wall, and detritus) of each larva every minute. There were significant
      differences in behaviors among the three detritus types and the four species
      (Culex generally different than Aedes), as well as a significant interaction
      between depth and detritus type. Consistent with predictions, Culex species spent
      more time filtering or resting, whereas Aedes larvae spent more time browsing on
      detritus. However, all four species changed their behavior similarly among the
      different environments, and Cx. coronator exhibited some similar behaviors as the
      two Aedes species. These behavioral differences may aid in explaining performance
      differences between different species and outcomes of interspecific encounters,
      which in turn can affect adult emergence and patterns of disease.

PMID- 24724287
TI  - Body size, blood feeding activity, and fecundity of Psorophora howardii,
      Psorophora ciliata, and Psorophora ferox (Diptera: Culicidae).
AB  - Field-collected female Psorophora howardii (Coquillett), Psorophora ciliate (F.),
      and Psorophora ferox (Humboltd) mosquitoes were tested in laboratory conditions
      to measure body size, blood engorgement duration, bloodmeal size, fecundity, and
      egg morphology. Mean bloodmeal size was significantly different among the three
      species of mosquitoes, whereas there was no difference in blood engorgement
      duration. Mean body weights and wing lengths of Ps. howardii and Ps. ciliata were
      significantly greater than Ps.ferox. Seven days after bloodmeals, oviposition
      rates for Ps. howardii, Ps. ciliata, and Ps.ferox were 18.8, 56.2, and 0%,
      respectively. The mean number of total eggs produced per female for the three
      species was 59, 81, and 73, respectively. Mean egg lengths of Ps. howardii and
      Ps. ciliata were significantly greater than Ps.ferox, and egg diameters for each
      of the three species were significantly different from one another. Length per
      diameter ratios of Ps. howardii and Ps. ciliata were significantly smaller than
      Ps. ferox. Bloodmeal size was positively related to body weight, but not related
      to blood engorgement duration, and the total egg number was positively related to
      bloodmeal size.

PMID- 24724288
TI  - Susceptibility and irritability of adult forms of main malaria vectors against
      insecticides used in the indoor residual sprays in Muzaffargarh District,
      Pakistan: a field survey.
AB  - In southern Punjab, Pakistan, Muzaffargarh District is known to have insecticide
      resistant Anopheles and drug-resistant Plasmodium spp. In this part of the
      country, five anopheline mosquitoes, Anopheles stephensi Liston, Anopheles
      culicifacies Giles, Anopheles fluviatilis James, Anopheles superpictus Grassi,
      and Anopheles subpictus Grassi (Diptera: Culicidae) are known as malaria vectors.
      Among these, An. culicifacies is the primary and An. stephensi is the secondary
      malaria vector. Outbreaks of malaria usually occur after rainy episodes. We
      conducted field surveys to collect field strains of An. culicifacies and An.
      stephensi mosquitoes from different areas of Muzaffargarh District. We determined
      susceptibility and irritability levels of their adult stages to the
      discriminative dose of different insecticides. For this purpose, we used World
      Health Organization's established criteria for assessment. Mortality was
      calculated after 1 h exposure and for 24 h recovery period for various
      insecticides. An. stephensi was found to be significantly resistant to
      dichlorodiphenyltrichloroethane (DDT, an organochlorine), dieldrin (a chlorinated
      hydrocarbon), and malathion (organophosphorus), with lethal times (LT50) of
      83.17, 52.48, and 37.53, respectively. However, the species was significantly
      sensitive to permethrin, deltamethrin (pyrethroids), and fenitrothion
      (organophosphate) with LT50 of 2.85, 2.34, and 13.18, respectively. Among these,
      permethrin showed more promising results against adult An. stephensi. When
      analyzed for irritancy, we found that among pyrethroids, permethrin was the most
      irritant insecticide for both An. stephensi and An. culicifacies. DDT and
      dieldrin showed least irritancy with 0.42 +/- 0.08 and 0.77 +/- 0.12 takeoffs per
      minute per adult, respectively, against An. stephensi. The mean number of
      takeoffs per minute per adult with permethrin showed significant irritancy for
      permethrin when compared with DDT. Based on this study, we conclude that the use
      of organochlorine (DDT) and chlorinated hydrocarbon (dieldrin) should not be
      reintroduced in Malaria Control Programme in Pakistan until there is enough
      evidence to do so at any stage in future, and the use of pyrethroids should
      continue, with preference to permethrin for better control of malariaby indoor
      residual spraying.

PMID- 24724289
TI  - Performance of the plant-based repellent TT-4302 against mosquitoes in the
      laboratory and field and comparative efficacy to 16 mosquito repellents against
      Aedes aegypti (Diptera: Culicidae).
AB  - Repellent efficacy of the plant-based repellent, TT-4302 (5% geraniol), was
      compared with 16 other products in laboratory arm-in-cage trials against Aedes
      aegypti (L). Eight repellents (Badger, BioUD, Burt's bees, California Baby,
      Cutter Natural, EcoSMART, Herbal Armor, and SkinSmart) exhibited a mean
      repellency below 90% to Ae. aegypti at 0.5 h after application. Three repellents
      (Buzz Away Extreme, Cutter Advanced, and OFF! Botanicals lotion) fell below 90%
      repellency 1.5 h after application. TT-4302 exhibited 94.7% repellency 5 h
      posttreatment, which was a longer duration than any of the other repellents
      tested. The positive control, 15% DEET (OFF! Active), was repellent for 3 h
      before activity dropped below 90%. Additional arm-in-cage trials comparing TT
      4302 with 15% DEET were carried out against Anopheles quadrimaculatus Say. At 6 h
      after treatment, TT-4302 provided 95.2% repellency while DEET exhibited 72.2%. In
      North Carolina field trials, TT-4302 provided 100% repellency 5 h after
      application against Aedes albopictus Skuse while DEET provided 77.6% repellency.
      These results demonstrate that TT-4302 is an efficacious plant-based repellent
      that provides an extended duration of protection compared with many other
      commercially available products.

PMID- 24724290
TI  - Efficacy of products to remove eggs of Pediculus humanus capitis (Phthiraptera:
      Pediculidae) from the human hair.
AB  - Head lice infestations are very common in children aged between 3 and 12 yr old.
      The eggs of the head louse are difficult to remove and remain firmly attached to
      the hair even after any head louse treatment. Solid in vitro and in vivo evidence
      to support the use of any of the proposed products to facilitate nit removal is
      scarce. The objective of the current study was to determine the efficacy of
      several products to remove eggshells from human hair using an objective
      measurement procedure. Water and ordinary hair conditioner significantly
      facilitated the removal of nits in vitro. We found no difference between ordinary
      conditioner and products specifically marketed for the purpose of nit removal.
      Other products such as formic acid solution and almond oil did not have a
      beneficial effect.

PMID- 24724291
TI  - Evaluation of the effectiveness of mass trapping with BG-sentinel traps for
      dengue vector control: a cluster randomized controlled trial in Manaus, Brazil.
AB  - The objective of this study was to assess the effectiveness of BG-Sentinel (BGS)
      traps for mass trapping at the household level to control the dengue vector,
      Aedes aegypti (L.), in Manaus (Brazil) by performing a cluster randomized
      controlled trial. After an initial questionnaire and baseline monitoring, 6 out
      of 12 clusters were randomly allocated to the intervention arm, where
      participating premises received one BGS trap for mass trapping. The other six
      clusters did not receive traps and were considered as the control arm. Biweekly
      monitoring with BGS in both arms assessed the impact of mass trapping. At the end
      of the study, a serological survey was conducted and a second questionnaire was
      conducted in the intervention arm. Entomological monitoring indicated that mass
      trapping with BGS traps significantly reduced the abundance of adult female Ae.
      aegypti during the first five rainy months. In the subsequent dry season when the
      mosquito population was lower, no effect of mass trapping was observed. Fewer Ae.
      aegypti females were measured in the intervention arm during the next rainy
      period, but no significant difference between arms was observed. The serological
      survey revealed that in participating houses of mass trapping areas recent dengue
      infections were less common than in control areas, although this effect was not
      statistically significant. The majority of participants responded positively to
      questions concerning user satisfaction. Our results suggest that BGS traps are a
      promising tool which might be deployed as part of dengue control programs;
      however, further investigations and larger scale studies are necessary.

PMID- 24724292
TI  - Laboratory selection of resistance to spinosad in Culex quinquefasciatus
      (Diptera: Culicidae).
AB  - A southern house mosquito Culex quinquefasciatus Say colony was established from
      surviving late instars and pupae from a semifield evaluation on Natular XRG (a
      granular formulation containing 2.5% spinosad). The initial lethal levels
      ofNatular XRG against this colony were determined in the laboratory for the first
      generation progeny (designated as F1). Selection pressure was applied at LC70-90
      levels to 10,000-15,000 late third- and early fourth-instar larvae of each
      generation with Natular XRG. Susceptibility changes in response to selection were
      determined every other generation, where a gradual and steady decline in
      susceptibility occurred from generation F1 to F35, followed by significant
      decline from generations F37 to F45 For reference purposes, susceptibility of
      freshly collected wild populations as well as a laboratory colony of the same
      species was also determined concurrently, which fluctuated within a slightly
      wider range for the wild populations and a tighter range for the laboratory
      colony. By comparing with wild populations and laboratory reference colony,
      tolerance to spinosad was observed from generations up to F9 in the selected
      population. Resistance levels increased gradually from generation F11 to F35, and
      elevated significantly from generations F37 to F45, when resistance ratios
      reached 1,415.3- to 2,229.9-fold at LC50 and 9,613.1- to 17,062.6-fold at LC90.
      Possible mechanisms of resistance development to spinosad were discussed.

PMID- 24724293
TI  - Cross resistances in spinosad-resistant Culex quinquefasciatus (Diptera:
      Culicidae).
AB  - A Culex quinquefasciatus Say colony was selected for 45 generations at LC70-90
      levels using Natular XRG, a granular formulation of 2.5% spinosad for induction
      of spinosad resistance. Resistance to spinosad was noticed in early generations
      (F1-F9). Resistance levels increased gradually from generations F11-F35, and
      elevated significantly from generation F37 through F47, when resistance ratios
      reached 2,845-2,907-fold at LC50 and 11,948-22,928-fold at LC90 The spinosad
      resistant Cx. quinquefasciatus colony was found not to be cross-resistant to
      Bacillus thuringiensis israelensis (Bti), a combination of Bti and Bacillus
      sphaericus, methoprene, pyriproxyfen, diflubenzuron, novaluron, temephos, or
      imidacloprid. However, it showed various levels of cross-resistance to B.
      sphaericus, spinetoram, abamectin, and fipronil. Conversely, a laboratory colony
      of Cx. quinquefasciatus that is highly resistant to B. sphaericus did not show
      cross-resistance to spinosad and spinetoram. Field-collected and laboratory
      selected Cx. quinquefasciatus that showed low to moderate resistance to
      methoprene did not show cross-resistance to spinosad and spinetoram. Mechanisms
      of cross-resistance among several biorational pesticides were discussed according
      to their modes of actions.

PMID- 24724294
TI  - Sublethal effect of pyriproxyfen released from a fumigant formulation on
      fecundity, fertility, and ovicidal action in Aedes aegypti (Diptera: Culicidae).
AB  - Dengue and dengue hemorrhagic fever are mosquito-borne viral diseases that
      coincide with the distribution of Aedes aegypti (L.), the primary vector in the
      tropical and semitropical world. With no available vaccine, controlling the
      dengue vector is essential to prevent epidemics. The effects of the insect growth
      regulator pyriproxyfen on Ae. aegypti adults that survived a treatment with a
      sublethal dose were investigated in the laboratory, including effects on their
      reproductive potential. Pyriproxyfen was released from a fumigant formulation at
      a dose causing 20 or 40% emergence inhibition (%EI). Females were dissected
      before and after blood feeding and the basal follicle number was counted. There
      were no differences between the control and treated group on the basal follicle
      number for both doses used. Fertility and fecundity were reduced at a
      concentration of EI40 but no at EI20. There was no ovicidal effect of
      pyriproxyfen by immersion of eggs in treated water neither when the females laid
      their eggs on a pyriproxyfen-treated surface. This work shows that sublethal
      doses of pyriproxyfen can have effects on fertility and fecundity ofAe. aegypti
      females, which together with its larvicidal activity could contribute to an
      overall decrease in a given population.

PMID- 24724295
TI  - Residual effectiveness of lambda-cyhalothrin harbourage sprays against foliage
      resting mosquitoes in north Queensland.
AB  - The residual efficacy of lambda-cyhalothrin sprayed on foliage was evaluated
      against various mosquito species in sections of forest in Cairns, Queensland,
      Australia Weekly sweep-net collections in treated and untreated areas before and
      after spraying showed 87-100% reductions in mosquito numbers for the first 9 wk
      postspray. After that period, reductions fluctuated but remained >71% up to 14 wk
      posttreatment. Mosquito mortality ranged from 96 to 100% in contact bioassays of
      treated leaves during the 14 wk study. Our results demonstrate that spraying
      harborage vegetation with lambda-cyhalothrin is an extremely effective strategy
      for the control of sylvan and peridomestic mosquito species in tropical north
      Queensland.

PMID- 24724296
TI  - Knockdown resistance allele frequencies in North American head louse (Anoplura:
      Pediculidae) populations.
AB  - The study examines the extent and frequency of a knockdown-type resistance allele
      (kdr type) in North American populations of human head lice. Lice were collected
      from 32 locations in Canada and the United States. DNA was extracted from
      individual lice and used to determine their zygosity using the serial invasive
      signal amplification technique to detect the kdr-type T917I (TI) mutation, which
      is most responsible for nerve insensitivity that results in the kdr phenotype and
      permethrin resistance. Previously sampled sites were resampled to determine if
      the frequency of the TI mutation was changing. The TI frequency was also
      reevaluated using a quantitative sequencing method on pooled DNA samples from
      selected sites to validate this population genotyping method. Genotyping
      substantiated that TI occurs at high levels in North American lice (88.4%).
      Overall, the TI frequency in U.S. lice was 84.4% from 1999 to 2009, increased to
      99.6% from 2007 to 2009, and was 97.1% in Canadian lice in 2008. Genotyping
      results using the serial invasive signal amplification reaction (99.54%) and
      quantitative sequencing (99.45%) techniques were highly correlated. Thus, the
      frequencies of TI in North American head louse populations were found to be
      uniformly high, which may be due to the high selection pressure from the
      intensive and widespread use of the pyrethrins- or pyrethroid-based pediculicides
      over many years, and is likely a main cause of increased pediculosis and failure
      of pyrethrins- or permethrin-based products in Canada and the United States.
      Alternative approaches to treatment of head lice infestations are critically
      needed.

PMID- 24724297
TI  - Cytotoxicity of piperamides towards Aedes aegypti (Diptera: Culicidae).
AB  - The effectiveness of the amides piplartine and piperlonguminine isolated from
      Piper species for controlling L3 and L4 of Aedes aegypti (L.) was assessed
      through bioassays at concentrations ranging from 1 to 300 g/l ml. Piplartine
      reduced the mosquito development period and caused larval mortality only at
      concentrations > 100 microg/ml, whereas piperlonguminine resulted in an extended
      period of mosquito development (10 microg/ml) and caused 100% larval mortality
      (30 microg/ml) within 24 h. The toxicity and cytotoxic effects of
      piperlonguminine on epithelial cells of the digestive system of Ae. aegypti were
      viewed using transmission electron microscopy, which indicated vacuolization of
      cytoplasm, mitochondrial swelling and leaking of nuclear material.
      Piperlonguminine was the more effective amide, showing toxic activity with LD50
      of approximately 12 microg/ml against the larvae of Ae. aegypti.

PMID- 24724298
TI  - Distribution and mosquito hosts of Chaoyang virus, a newly reported flavivirus
      from the Republic of Korea, 2008-2011.
AB  - In total, 183,602 female culicine mosquitoes were captured by Mosquito Magnet,
      black light, and New Jersey light traps, and manual aspiration of resting blood
      fed mosquitoes, in the Republic of Korea from 2008 to 2011. Culicine mosquitoes
      were identified to species, placed in pools of up to 30 mosquitoes each, and
      screened for flavivirus RNA by using an SYBR green I-based reverse transcription
      polymerase chain reaction assay. Thirty-two of the 8,199 pools assayed were
      positive by quantitative polymerase chain reaction for Chaoyang virus (CHAOV), an
      insect-specific virus [26 Aedes vexans nipponii Theobald, 3 Culex pipiens L., 1
      Aedes albopictus (Skuse), 1 Aedes bekkui Mogi, and 1 Armigeres subalbatus
      (Coquillett)]. The maximum likelihood estimations (estimated number of virus
      positive mosquitoes/1,000 mosquitoes) for Ae. bekkui, Ae. albopictus, Ar.
      subalbatus, Ae. vexans nipponii, and Cx. pipiens positive for CHAOV were 5.37,
      3.29, 0.77, 0.27, and 0.26, respectively. CHAOV is an insect-specific virus, and
      there is currently no evidence to suggest a role in animal or human disease.

PMID- 24724301
TI  - Understanding that "R" or "L" word ... and addressing the mysterious black box.

PMID- 24724300
TI  - Discovery of a bird-parasitic fly, Carnus orientalis (Diptera: Carnidae), in
      Japan, with bionomic remarks and a key to Carnus species.
AB  - A bird-parasitic fly, Carnus orientalis Maa, 1968, is recorded for the first time
      from Japan, and it is taxonomically reexamined on the basis of specimens
      collected in Okinawa Prefecture. Adult flies were found from nestlings of Ryukyu
      scops owl (Otus elegans Cassin, 1852), which is a new host for C. orientalis.
      Bionomic remarks regarding C. orientalis are presented, and akey to the world
      species of Carnus is also provided.

PMID- 24724299
TI  - Vacant lots: productive sites for Aedes (Stegomyia) aegypti (Diptera: Culicidae)
      in Merida City, Mexico.
AB  - We assessed the potential for vacant lots and other nonresidential settings to
      serve as source environments for Aedes (Stegomyia) aegypti (L.) (Diptera:
      Culicidae) in Merida City, Mexico. Mosquito immatures were collected, during
      November 2011-June 2013, from residential premises (n = 156 site visits) and
      nonresidential settings represented by vacant lots (50), parking lots (18), and
      streets or sidewalks (28). Collections totaled 46,025 mosquito immatures of 13
      species. Ae. aegypti was the most commonly encountered species accounting for
      81.0% of total immatures, followed by Culex quinquefasciatus Say (12.1%). Site
      visits to vacant lots (74.0%) were more likely to result in collection of Ae.
      aegypti immatures than residential premises (35.9%). Tires accounted for 75.5% of
      Ae. aegypti immatures collected from vacant lots. Our data suggest that vacant
      lots should be considered for inclusion in mosquito surveillance and control
      efforts in Merida City, as they often are located near homes, commonly have
      abundant vegetation, and frequently harbor accumulations of small and large
      discarded water-holding containers that we now have demonstrated to serve as
      development sites for immature mosquitoes. In addition, we present data for
      associations of immature production with various container characteristics, such
      as storage capacity, water quality, and physical location in the environment.

PMID- 24724302
TI  - McCay Vernon: a life worth celebrating.

PMID- 24724303
TI  - Assessment and reading paradigms: a response to John Luckner.

PMID- 24724304
TI  - Luckner's response to Andrews.

PMID- 24724305
TI  - Cawthon, S., & Leppo, R. (2013). Assessment accommodations on tests of academic
      achievement for students who are deaf or hard of hearing: a qualitative meta
      analysis of the research literature. American Annals of the Deaf 158 (3), 363
      376.

PMID- 24724306
TI  - Developing preschool deaf children's language and literacy learning from an
      educational media series.
AB  - With the increase in research on multiliteracies comes greater interest in
      exploring multiple pathways of learning for deaf children. Educational media have
      been increasingly examined as a tool for facilitating the development of deaf
      children's language and literacy skills. The authors investigated whether
      preschool deaf children (N = 31) acquired targeted American Sign Language and
      literacy skills after viewing one video from an educational video series in ASL.
      Descriptive statistics were gathered and a split-plot ANOVA was conducted to
      determine whether targeted literacy scores increased from pretest to posttest and
      whether scores varied by baseline ASL skills. A significant improvement was found
      in the skills targeted in the video, which occurred regardless of the level of
      baseline ASL skills. The findings support the claim that learning ASL and
      literacy skills through educational media may benefit deaf children with varied
      levels of exposure to ASL.

PMID- 24724307
TI  - Deaf and hard of hearing adolescents' processing of pictures and written words
      for taxonomic categories in a priming task of semantic categorization.
AB  - Inspired by research by Li, Yi, and Kim (2011), the authors examined Chinese deaf
      and hard of hearing adolescents' responses to pictures for taxonomic categories
      of basic level (exemplar pictures) preceded by exemplar pictures, and to written
      words for taxonomic categories of basic level (exemplar words) preceded by
      exemplar words or by written words for those of superordinate level (category
      names), in a priming task of semantic categorization. Stimulus onset asynchrony
      (SOA) was manipulated. The adolescents were less aware of taxonomic relations and
      were more likely to show the advantage of pictures over written words than their
      hearing counterparts. Their processing of exemplar primes steadily deepened as
      SOA increased, reaching its deepest level when SOA was 237 ms. Their processing
      of category names seemed immune to changes in SOA, probably because of their
      fuzzy representations of taxonomic categories of superordinate level.

PMID- 24724308
TI  - Accommodations quality for students who are d/Deaf or hard of hearing.
AB  - Students who are d/Deaf or hard of hearing often receive accommodations that are
      intended to increase access to the educational environment. The authors provide
      the results of a large national study of accommodations use in secondary and
      postsecondary settings. The article focuses on three aspects of accommodations
      use: access, quality, and consistency. The participants were 1,350 professionals
      working with a diverse group of students who were d/Deaf or hard of hearing in a
      variety of roles, including educators, administrators, interpreters, vocational
      rehabilitation agency staff, and allied service providers. Data were collected
      from both a national survey and a series of focus groups conducted over a 1-year
      period. The authors discuss the results in light of the crucial nature of
      accommodations during the transition into a variety of educational, training, and
      employment options.

PMID- 24724310
TI  - Collaborating to better serve you.

PMID- 24724309
TI  - Effects of expanded and standard captions on deaf college students' comprehension
      of educational videos.
AB  - Twenty-two college students who were deaf viewed one instructional video with
      standard captions and a second with expanded captions, in which key terms were
      expanded in the form of vocabulary definitions, labeled illustrations, or concept
      maps. The students performed better on a posttest after viewing either type of
      caption than on a pretest; however, there was no difference in comprehension
      between standard and expanded captions. Camtasia recording software enabled
      examination of the extent to which the students accessed the expanded captions.
      The students accessed less than 20% of the available expanded captions. Thus, one
      explanation for the lack of difference in comprehension between the standard and
      expanded captions is that the students did not access the expanded captions
      sufficiently. Despite limited use of the expanded captions, the students stated,
      when interviewed, that they considered these captions beneficial in learning from
      the instructional video.

PMID- 24724311
TI  - An interview with ACHE's 2014-2015 Chairman.

PMID- 24724312
TI  - The power of analytics: harnessing big data to improve the quality of care.

PMID- 24724313
TI  - Physician engagement: strengthening the culture of quality and safety.

PMID- 24724314
TI  - Leadership training for all.

PMID- 24724316
TI  - Proposed ethical guidelines for quality improvement.

PMID- 24724315
TI  - Controlling your Email.

PMID- 24724317
TI  - Fighting food deserts to better serve patients.

PMID- 24724318
TI  - A friend across the globe.

PMID- 24724319
TI  - Coming in October: ICD-10.

PMID- 24724320
TI  - Enhancing the mentor-mentee relationship.

PMID- 24724321
TI  - Partnering to expand strategic discourse.

PMID- 24724322
TI  - Integrating behavioral health into primary care.

PMID- 24724323
TI  - The future of hospitals in America.

PMID- 24724324
TI  - Lifelong learning and the healthcare executive.

PMID- 24724325
TI  - You have a lot of nerve: an insider's perspective on pain.

PMID- 24724327
TI  - Pediatric anaphylaxis.

PMID- 24724328
TI  - No free lunch.

PMID- 24724329
TI  - A coughing spell.

PMID- 24724330
TI  - Intubation alternative.

PMID- 24724331
TI  - Upstroke ventilation.

PMID- 24724332
TI  - Improving airway management.

PMID- 24724333
TI  - Infection inspection: screening & managing sepsis in the prehospital setting,
      part 2 of 2.

PMID- 24724334
TI  - Hazmat update.
AB  - EMS responders to hazmat incidents face significant challenges; however,
      integration of medical care providers into the planning process for hazmat
      incidents can facilitate a more efficient response. The competencies found in
      NFPA 473 provide thorough guidance for EMS professionals during planning,
      preparation and response to hazmat/ WMD incidents. JEMS

PMID- 24724335
TI  - Neonatal & infant ventilation methods.

PMID- 24724336
TI  - EMS 10: innovators in EMS 2013.

PMID- 24724337
TI  - A different kind of patient.

PMID- 24724338
TI  - Responder resilience.

PMID- 24724339
TI  - Practice the way we play.

PMID- 24724340
TI  - Compassion for our own.

PMID- 24724341
TI  - Taboo tales.

PMID- 24724342
TI  - Take the lead.

PMID- 24724343
TI  - Exploring quality of life in critically ill tracheostomy patients: a pilot study.
AB  - BACKGROUND: Tracheostomies are performed to improve health-related quality of
      life (QOL) in patients requiring prolonged mechanical ventilation. As the lengths
      of stay in intensive care units (ICU) increase and higher rates of tracheostomies
      are becoming more prevalent, issues regarding patient perceptions of their own
      prognoses and outcomes after tracheostomy can considerably impact QOL and in turn
      their care and recovery. Whether tracheostomy improves QOL, however, has not been
      studied adequately. Current studies investigating QOL have been limited to pre-
      and post-ICU admission, have relied on surrogate measures such as clinical
      outcomes and proxy reports, and have used inadequate instruments, failing to
      capture all domains of QOL. Studies using a robust instrument to investigate QOL
      in the ICU before and after tracheostomy are lacking. PURPOSE: To explore the
      feasibility of assessing patient-reported QOL of mechanically ventilated ICU
      patients with a tracheostomy. METHODS: A prospective longitudinal pilot study was
      conducted in awake and interactive patients who were mechanically ventilated in
      an ICU using a modified version of the University of Washington QOL
      Questionnaire. Data were collected at three measurement time points--Time 0 (T0),
      Time 1 (T1), and Time 2 (T2)--five days apart. The QOL scores were compared
      between patients who received a tracheostomy and those who did not, as well as
      between those who received a tracheostomy before and after ten days of
      intubation. RESULTS: The modified University of Washington Quality of Life
      (UWQOL) questionnaire was easily administered by one person. Patients were able
      to answer all the questions by writing or pointing at the answer choices with
      either an endotracheal or a tracheostomy tube in place. The mean time to complete
      the questionnaire was 7.5 minutes. QOL scores ranging from 0 to 800 were
      administered. Pain and speech were the most important domains contributing to
      QOL. The median QOL scores were 242 at T0 and T1, and 383 at T2. There was a
      significant difference in the median QOL scores between those who received a
      tracheostomy (458) and those who remained endotracheally intubated (175) at T2.
      Similarly, patients who received early tracheostomy reached a higher QOL score by
      T1 compared to those who did not (417 vs. 267). CONCLUSIONS: This pilot study
      demonstrates that a modified questionnaire to assess QOL in patients with
      prolonged mechanical ventilation is feasible, and useful in capturing artificial
      airway-related QOL. Further studies should evaluate the utility of this tool in a
      larger study.

PMID- 24724344
TI  - Clinical consensus statement: tracheostomy care-putting statements into action!
AB  - A clinical consensus statement (CCS) on tracheostomy care for adults and children
      was developed to improve care for this patient population. Statements were
      identified using a modified Delphi method with the goal to reduce practice
      variations among tracheostomy patients. Integration of these statements into
      daily practice in the care setting is the next step for information
      dissemination. The CCS affected current policies, procedures, protocols, staff
      education, and patient education. The process of updating practice at a large
      tertiary care center is described using evidence-based implementation strategies.

PMID- 24724345
TI  - Heat and moisture exchange devices for patients undergoing total laryngectomy.
AB  - Patients undergoing total laryngectomy face the challenge of an altered anatomy
      with the resultant changes in quality of life and significant requirements for
      post-operative care. Increased production of secretions and sputum, the need for
      ongoing suctioning, and the formation of stomal crusting require meticulous post
      operative care. The use of Heat and Moisture Exchange (HME) devices has been
      shown to decrease the effect of these factors. This article describes the nature
      of these devices and their use. The literature is reviewed regarding the long
      term benefits and new data are presented suggesting an immediate post-operative
      benefit as well. Finally, costs and other considerations for successful use of
      HME devices are presented.

PMID- 24724346
TI  - Why is government relations important to my nursing practice?

PMID- 24724347
TI  - High level disinfection of scopes: solution temperature update.

PMID- 24724348
TI  - [Editorial policy of the Japanese Journal of Toxicology (semiofficial journal of
      the Japanese Association of Clinical Toxicology)].

PMID- 24724349
TI  - [On organizing the 36th annual meeting of the Japanese Society for Clinical
      Toxicology].

PMID- 24724350
TI  - [Molecular mechanism of acute acetaminophen intoxication].

PMID- 24724351
TI  - [Poisoning by the use of Datura plants].

PMID- 24724352
TI  - [Colchicum autumnale].

PMID- 24724353
TI  - [Narcissus].

PMID- 24724354
TI  - [Convallaria spp].

PMID- 24724355
TI  - [Tree tobacco Nicotiana glauca].

PMID- 24724356
TI  - [Hydrangea Hydrangea macrophylla].

PMID- 24724357
TI  - [Dermatitis caused by primulas].

PMID- 24724358
TI  - [Carbon monoxide poisoning: traditional condition with new problems].

PMID- 24724360
TI  - [Conservative treatment improved corrosive esophagitis and pneumomediastinum in a
      patient who ingested bleaching agent containing sodium hypochlorite and sodium
      hydroxide].
AB  - A 69-year-old man was admitted to the emergency department 3 hours after
      ingestion of a bleaching agent containing hypochlorous acid and sodium hydroxide
      in a suicide attempt. Enhanced chest computed tomography scans taken on admission
      indicated an edematous esophagus and air bubbles in the mediastinum. He underwent
      endotracheal intubation and mechanical ventilation until day 9 because of
      laryngeal edema. On day 10, his endoscopy indicated diffuse reddish mucosal
      hyperemia, erosions, and lacerated mucosal lesions in the esophagus that were
      indicative of grade 2b corrosive esophagitis. Treatment with a proton pump
      inhibitor was initiated, with which the condition of the esophagus improved, and
      on day 44, a slight stricture of the upper part of the esophagus was observed. He
      was discharged on day 64 without any complaints. The ingestion of sodium
      hypochlorite induces corrosive esophagitis and acute phase of gastritis.
      Ingestion of any corrosive agent is known as a risk factor for esophagus cancer
      in the long-term. In such cases with esophageal stricture, esophagectomy is
      recommended for preventing esophagus cancer. Considering the age of the patient,
      however, he did not undergo esophagectomy.

PMID- 24724359
TI  - [Cross-reactivity of Instant-View M-1 for detection of benzodiazepine-related
      drugs and their metabolites in urine].
AB  - Immunoassays are useful methods for the determination of regulated drugs in
      clinical and forensic laboratories. Although the Instant-View M-1 (IV M-1)
      immunoassay kit is frequently used to screen drugs in laboratories in Japan,
      basic information about the IV M-1 such as its specificity and reactivity is not
      available. In this study, we determined the specificity and cross-reactivity of
      IV M-1 for the detection of benzodiazepine-related drugs and their metabolites in
      urine. The IV M-1 could detect triazolobenzodiazepines such as triazolam in urine
      at concentrations > or = 300 ng/mL. However, thienodiazepines such as etizolam
      could not be detected because of lack of cross reactivity. A correlation was
      observed between the structure of the metabolites and the reactivity of the kit;
      4-hydroxy metabolites of alprazolam and triazolam were detectable, whereas a
      hydroxy metabolites were not. Furthermore, 7-amino metabolites such as nitrazepam
      could not be detected at any concentration, including high concentrations. The
      specificity and reactivity of various kits used for detection of drugs in urine
      are different. Therefore, it is necessary to consider the basic features of the
      kit used while assessing the results obtained.

PMID- 24724361
TI  - [Case of valproic acid overdose treated by hemodialysis].

PMID- 24724362
TI  - [Blood concentration useful in the diagnosis and treatment of poisoning].

PMID- 24724363
TI  - [Practical analysis of toxic substances useful for clinical toxicology (5).
      Introduction of a new simple analysis of acetaminophen; ZAP tox Acetaminophen
      Test].

PMID- 24724364
TI  - [Hydroxocobalamin].

PMID- 24724365
TI  - [Educational activities that JPIC is implementing on residents and pharmacy
      students].

PMID- 24724366
TI  - [Cardiomyopathy:progress in diagnosis and treatments. Editorial: Reconsideration
      of cardiomyopathy from the forefront medicine].

PMID- 24724367
TI  - [Cardiomyopathy: progress in diagnosis and treatments topics: I. New
      classification based on etiology of cardiomyopathy; 1. Classification of
      cardiomyopathy--its past and present status].

PMID- 24724368
TI  - [Cardiomyopathy: progress in diagnosis and treatments topics: I. New
      classification based on etiology of cardiomyopathy; 2. Genomics of
      cardiomyopathy].

PMID- 24724369
TI  - [Cardiomyopathy: progress in diagnosis and treatments. Topics: II. Secondary
      cardiomyopathy; 1. Cardiac Fabry disease].

PMID- 24724370
TI  - [Cardiomyopathy: progress in diagnosis and treatments. Topics: II. Secondary
      cardiomyopathy; 2. Cardiac sarcoidosis].

PMID- 24724371
TI  - [Cardiomyopathy: progress in diagnosis and treatments. Topics: II. Secondary
      cardiomyopathy; 3. Takotsubo cardiomyopathy: clinical features and underlying
      mechanisms].

PMID- 24724372
TI  - [Cardiomyopathy: progress in diagnosis and treatments. Topics: II. Secondary
      cardiomyopathy; 4. Arrhythmogenic right ventricular cardiomyopathy].

PMID- 24724373
TI  - [Cardiomyopathy: progress in diagnosis and treatments. Topics: II. Secondary
      cardiomyopathy; 5. Noncompaction of the ventricular myocardium].

PMID- 24724374
TI  - [Cardiomyopathy: progress in diagnosis and treatments. Topics: III. Diagnosis
      leading to selection of therapy; 1. Patient history, symptom and physical
      findings of cardiomyopathy].

PMID- 24724375
TI  - [Cardiomyopathy: progress in diagnosis and treatments. Topics: III. Diagnosis
      leading to selection of therapy: 2. Biomarker].

PMID- 24724376
TI  - [Cardiomyopathy: progress in diagnosis and treatments. Topics: III. Diagnosis
      leading to selection of therapy; 3. Echocardiography].

PMID- 24724377
TI  - [Cardiomyopathy: progress in diagnosis and treatments. Topics: III. Diagnosis
      leading to selection of therapy; 4. Imaging of cardiomyopathy].

PMID- 24724378
TI  - [Cardiomyopathy: progress in diagnosis and treatments. Topics: IV. Selection of
      therapy for improvement of prognosis and QOL; 1. Up-to-date on drug therapy for
      chronic heart failure].

PMID- 24724379
TI  - [Cardiomyopathy: progress in diagnosis and treatments. Topics: IV. Selection of
      therapy for improvement of prognosis and QOL; 2. Cardiac resynchronization
      therapy].

PMID- 24724380
TI  - [Cardiomyopathy: progress in diagnosis and treatments. Topics: IV. Selection of
      therapy for improvement of prognosis and QOL; 3. Ventricular assist device in
      cardiology].

PMID- 24724381
TI  - [Cardiomyopathy: progress in diagnosis and treatments. Topics: IV. Selection of
      therapy for improvement of prognosis and QOL; 4. Current conditions and future
      directions of heart transplantation in Japan].

PMID- 24724382
TI  - [Discussion meeting on the how to manage cardiomyopathy].

PMID- 24724383
TI  - [Case report; a case of Hashimoto's thyroiditis mimicking dementia with Lewy
      bodies (DLB)].

PMID- 24724384
TI  - [Case report; myeloid sarcoma with systemic lymphadenopathy, skin and
      gastrointestinal infiltration].

PMID- 24724385
TI  - [The cutting edge of medicine: pathophysiology and treatment of
      myeloproliferative neoplasms].

PMID- 24724386
TI  - [Report from Kinki Chapter Educational Seminar. The forefront of internal
      medicine in care for elderly patients].

PMID- 24724387
TI  - [Series: Clinical study from Japan and its reflections; atorvastatin, etidronate,
      or both in patients at high risk for atherosclerotic aortic plaques: a
      randomized, controlled trial].

PMID- 24724388
TI  - [Series: For attending physicians; seeking to understand the diversity of
      medicine; what is community medicine?].

PMID- 24724389
TI  - [Series: Physicians and disaster medical care: Third stage, Management and
      education for disaster medicine: disaster medical coordination system (1). Mid
      Niigata Prefecture earthquake in 2004 & Niigataken Chuetsu-oki earthquake in
      2007].

PMID- 24724390
TI  - [How does the physician interpret the patient's narrative as it relates to the
      physical exam?; A case of spinocerebellar degeneration with peripheral
      neuropathy].

PMID- 24724391
TI  - [How does the physician interpret the patient's narrative as it relates to the
      physical exam?: Consideration of differential diagnosis based on double vision
      and vertigo].

PMID- 24724392
TI  - [Pathogenesis of lymphoma].

PMID- 24724393
TI  - [The progress of laboratory medicine and diagnostic procedures in lymphoma and
      its future prospects].
AB  - As for the lymphoma, the cell origin and the tumorigenic process are not unitary
      and the biological property of lymphoma is various. The cellular origin and the
      etiology of the lymphoma were gradually elucidated by immunological,
      cytogenetical and molecular biological progress. Recently the pathological
      classification of lymphoma was gathered in WHO-2008 classification. On the other
      hand, changes of the clinical staging system and the criteria of curative effects
      of lymphoma therapy depended on the progress of the diagnostic imaging especially
      the computed tomography (CT) and the 18F-fluorodeoxyglucose positron emission
      tomography(FDG-PET). They were gathered in International Working Group (IWG)-2007
      criteria. As for the diagnostic classification and the criteria of the curative
      effects of treatments, update and revision will be unavoidable with accumulation
      of proposal of new disease concepts and development of the laboratory procedure
      in future.

PMID- 24724394
TI  - [The progress in treatment for malignant lymphomas and the future direction].
AB  - The prognosis of patients with malignant lymphoma was improved with the
      development of multi-agent chemotherapy, radiotherapy and monoclonal antibody.
      Half of aggressive non-Hodgkin lymphomas which were previously considered to be
      incurable, are able to achieve cure after appropriate treatment. Furthermore,
      natural history of indolent B-cell lymphoma was improved by the introduction of
      anti-CD20 monoclonal antibody. Because Hodgkin lymphoma is one of the most
      favorable prognosis among adult malignancies, current studies focus on a
      reduction of acute and late toxicity by decreasing treatment intensity. On the
      other hand, there has been tremendous advances in the pathology, biology and
      molecular characterization of lymphomas. As a result, novel molecular targeted
      agents have been developed in recent years. The treatment for malignant lymphoma
      is currently undergoing a paradigm shift away from conventional chemotherapy
      toward molecular targeted agents based on the biological understanding.

PMID- 24724395
TI  - [Blood test for malignant lymphoma].
AB  - Malignant lymphoma is a neoplastic disease that develops in the lymph system,
      which consists of various different subtypes. In addition, the differential
      diagnosis of malignant lymphoma includes infections, autoimmune diseases,
      allergic diseases, endocrine disorders, and so on. Therefore accurate diagnosis
      is very important to decide therapeutic strategy. Blood test is the most common
      examination in clinical practice and used extensively for evaluating etiology,
      pathology, disease state, efficacy of treatment and disease prognosis of
      lymphoma. We are required to understand the characteristics of blood examinations
      correctly and use them appropriately in daily medical practice. Here, we
      introduce some blood examinations used for treatment of lymphoma.

PMID- 24724396
TI  - [Flow cytometry].
AB  - Flow cytometry (FCM), which has been elaborated and refined in conjunction with
      the development of both immunological engineering and information technology, is
      now indispensable for the diagnosis and treatment of patients with leukemia and
      lymphoma. FCM had better be regarded as being complementary to, but not
      competitive with, immunohistochemistry. Histopathologic features are often useful
      not only for interpretation of the FCM data, but also in evaluating quality of
      samples used for FCM. In interpretation of the data, one should not put excessive
      emphasis on bar chart, because conversion of dot plotting to it is associated
      with loss of many data. Although FCM gives digital data on each thousands of
      cells, correct interpretation of the data requires an analogue standpoint.

PMID- 24724397
TI  - [Chromosome analysis and genetic testing].
AB  - Chromosomal and genetic tests are essential to establish correct diagnoses of the
      lymphoma. When the tissue examination is planned, these should be done
      simultaneously with the morphological and immunophenotypic evaluations.
      Chromosome analyses can identify the genomic alterations of tumor cells. Some
      chromosome abnormalities define disease subtypes. For example, recurrent 14q32
      translocations involving the immunoglobulin heavy chain locus support the
      diagnosis of B-cell lymphoma, and their translocation partners identify the
      types. In contrast, genetic testings are performed to confirm the presence of
      certain abnormalities including gene rearrangements, mutations, amplifications
      and deletions in each case. These results provide us detailed information for
      diagnosis, prognosis, and choice of therapy.

PMID- 24724398
TI  - [Imaging examinations in lymphoma].
AB  - Imaging examinations are necessary in the various clinical situations of
      malignant tumors including lymphoma, which are differential diagnosis, staging,
      evaluation of response to treatment, prognosis prediction or early diagnosis of
      relapse. Generally morphologic imaging(such as CT, MRI and US) and functional
      imaging(such as gallium scintigraphy and FDG-PET) are used for malignant
      lymphoma. Especially, CT and FDG-PET have quite important roles for multicenter
      studies of treatment according to the response criteria of lymphoma. In this
      chapter, the features of each imaging examinations in lymphoma were explained. In
      addition, interim PET was mentioned at the end, which is considered as a
      promising biomarker for stratifying treatment of lymphoma.

PMID- 24724399
TI  - [The frequency of malignant lymphoma subtypes based on World Health Organization
      (WHO) classification].
AB  - Diagnosis of malignant lymphoma is based on the 4th edition of World Health
      Organization (WHO) Classification of Tumours of Haematopoietic and Lymphoid
      Tissues. The frequency of malignant lymphoma subtypes depends on age, race and
      geography. In Asian countries, Hodgkin lymphoma and follicular lymphoma are less
      frequent compared to Western countries. However, the number of patients with
      follicular lymphoma is now increasing in Japan. In contrast, in Japan, adult T
      cell leukemia/lymphoma is more frequent than in Western and other Asian
      countries, because it relates to distribution of human T-cell leukemia virus type
      1(HTLV-1).

PMID- 24724400
TI  - [Pathologic diagnosis of mature B-cell lymphoma].
AB  - Procedure of pathologic diagnosis of mature B-cell lymphoma (BCL) was explained.
      A definition of mature B-cell is given to have surface immunoglobulin (sIg) and
      it is easily detected by flow cytometry(FCM), but not by immunohistochemistry
      (IHC). Mature BCLs are subdivided into low grade BCL showing diffuse
      proliferation of CD2+ B-cells with low MIB-1 index or nodular proliferation of B
      cells and high grade BCL showing diffuse proliferation of B-cells with high MIB-1
      index. To make a proper diagnosis for low and high grade BCL, respectively,
      secondary IHC with CD5, CD10, BCL-2, BCL-6, MUM-1 and cyclin D1 is needed.
      Detecting clonality of light chain of sIg, FCM is useful for mature BCL.

PMID- 24724401
TI  - [Pathological diagnosis of mature T/NK cell lymphoma].
AB  - Peripheral T-cell lymphoma (PTCL) and natural killer/T-cell lymphoma (NKTCL) are
      rare and heterogeneous forms of non-Hodgkin lymphoma (NHL) that, in general, are
      associated with a poor clinical outcome. In addition, many subtypes are present
      in the World Health Organization (WHO) classification of PTCL. To well classify
      and diagnose the PTCL, clinical, molecular, morphological and phenotypic data are
      necessary. For example, human T-cell leukemia virus type 1 (HTLV-I) provirus is
      necessary for the diagnosis of adult T-cell leukemia/lymphoma (ATLL). The t(2 :
      5) and ALK expression are necessary for anaplastic lymphoma kinase (ALK) positive
      anaplastic large cell lymphoma (ALK+ ALCL). Epstein-Barr virus (EBV) is necessary
      for NKTCL.

PMID- 24724402
TI  - [Pathological diagnosis of Hodgkin lymphoma].
AB  - This lymphoma was recognized by Thomas Hodgkin in 1832. In 1865, Samuel Wilks
      named it Hodgkin disease. Now, the term Hodgkin lymphoma (HL) is acceptable over
      Hodgkin disease. Since the neoplastic cells of the disease is well-recognized to
      be a lymphoid cell, especially B lymphocyte. In WHO classification published in
      2008, HLs are divided into two entities: Classical HL and nodular lymphocyte
      predominat HL. The former is composed of four different subtypes: nodular
      sclerosis (NS), mixed cellularity (MC), lymphocyte rich (LR), and lymphocyte
      depletion (LD). HL is characterized by the morphological feature comprising a
      minority of neoplastic cells, Hodgkin/Reed-Sternberg cells and popcorn (LP) cells
      and a majority of non-neoplastic reactive cells. Antigen receptor gene analyses
      by prevailing molecular methods and flow cytometry are not appropriate method for
      the diagnosis of HL, because of small number of neoplastic cells. They are,
      however, very useful in the differential diagnosis to rule out other lymphomas.
      Even the present when science progressed, pathological (morphological and
      immunohistochemical) examination is very worth for diagnosis of HL.

PMID- 24724403
TI  - [Staging and evaluation of bone marrow involvement in lymphoma].
AB  - Staging of lymphoma is important for predicting the prognosis and deciding on the
      treatment strategy for each patient. The Ann Arbor classification and its
      Cotswolds revised version are widely used, and now comprise the standard staging
      system for lymphoma. Bone marrow involvement is one of the most important factors
      in the staging system. Pathological patterns of lymphoma cell infiltration in the
      marrow are categorized into the following types: 1) nodular/patchy, 2)
      paratrabecular, 3) interstitial, 4) diffuse, and 5) intrasinusoidal. The
      frequency and patterns of bone marrow involvement in association with the
      subtypes of lymphoma are reviewed. PET/CT analysis has become a powerful method
      for staging lymphoma, and may complement or substitute for bone marrow biopsy in
      some subtypes of lymphoma.

PMID- 24724404
TI  - [Chemotherapy].
AB  - The progress of cancer chemotherapy has made a large contribution to the
      significant improvement of cure rate in patients with hematological malignancy
      including malignant lymphoma. Interpatient variability characterizes the
      disposition of many drugs. In the case of drugs with a wide therapeutic index,
      such variability is unlikely to affect either clinical efficacy or toxicity. With
      anticancer drugs, however, there is much less margin for error, due to their very
      narrow therapeutic index. Therefore, it is crucially important to understanding
      the mechanism of action, pharmacokinetics and pharmacodynamics of each anticancer
      drug in order to give chemotherapy in safety. Overview of the pharmacological
      functions of anticancer agent using in malignant lymphoma is the subject of this
      chapter.

PMID- 24724405
TI  - [Radiation therapy for malignant lymphoma].
AB  - Malignant lymphoma is usually radiosensitive and radiation therapy is an
      effective modality for local control of lymphoma. However, lymphoma is a typical
      systemic disease, and chemotherapy is performed for many cases. Recently, the
      late adverse events associated with radiotherapy (especially extended field
      radiation therapy), such as cardiovascular disease and secondary cancers, become
      a serious problem for long-term lymphoma survivors. In combination with
      chemotherapy, it is possible to reduce both the treatment volume and the overall
      treatment dose to minimise the risks of late adverse events.

PMID- 24724406
TI  - [Targeted therapy].
AB  - Rituximab, a genetically engineered chimeric monoclonal antibody that
      specifically binds to CD20, is the first monoclonal antibody approved for the
      treatment of B-cell lymphoma. It has been shown that rituximab exerts cytotoxic
      activities through CDC and ADCC, and that it directly induces apoptosis. The CD20
      protein has four transmembrane domains (tetraspan structure) and is not
      internalized following antibody binding, and is not shed or secreted into the
      circulation. Therefore, CD20 can serve as a target of antibody therapy. As the
      other anti-CD20 antibodies, there are ofatumumab and obinutuzumab, and clinical
      development is expected. In addition, histone deacetylate inhibitor or proteasome
      inhibitor as a new drugs for lymphoma in the future.

PMID- 24724407
TI  - [Current status of hematopoietic stem cell transplantation for malignant
      lymphoma].
AB  - The roles of high-dose chemotherapy/chemo-radiotherapy with either autologous or
      allogeneic hematopoietic stem cell supports in the treatment lymphoma continue to
      change. Introduction of molecular targeting agents and other new drugs to the
      standard chemotherapy have improved the treatment outcome significantly, and
      hematopoietic stem cell transplantation (HSCT) is not currently used as part of
      first-line therapy. As opposed to this, autologous HSCT are widely used for the
      treatment of relapsed or refractory lymphoma. Allogeneic HSCT is also
      increasingly being considered. However, the outcome of HSCT in
      relapsed/refractory lymphoma remains unsatisfactory, and a variety of molecular
      targeting approaches are currently being incorporated in order to improve the
      outcome of HSCT for lymphoma.

PMID- 24724408
TI  - [Treatment approaches for diffuse large B-cell lymphoma].
AB  - Diffuse large B-cell lymphoma(DLBCL) is the most common non-Hodgkin lymphoma, and
      is regarded as a heterogeneous group of lymphomas in terms of morphologic,
      immunologic, and cytogenetic features. The 2008 WHO classification divides DLBCL
      into subtypes based on clinical, morphological, immunological, and genetic
      features. The current standard of care for DLBCL is CHOP chemotherapy
      (cyclophosphamide, doxorubicin, vincristine, and prednisone) combined with
      rituximab, anti-CD20 antibody, allowing many patients to achieve disease cure.
      Despite of recent progress in improving patient survival, clinical outcomes are
      still unsatisfactory for certain subtypes of DLBCL. This review outlines the
      current treatment strategy for DLBCL and focuses on recent clinical trials in
      Japan for particular subgroups of DLBCL.

PMID- 24724409
TI  - [Follicular lymphoma].
AB  - Follicular lymphoma (FL) is the most popular indolent lymphoma. In discussing the
      appropriate first-line therapy, FL patients are divided into 3 clinical
      categories: 1) localized-stage FL in which local irradiation is recommended and
      30-50% of patients experience long progression-free survival, 2) low-tumor burden
      advanced-stage FL in which watchful waiting strategy is generally recommended, 3)
      high-tumor burden advanced-stage FL in which CHOP plus rituximab(R) is
      recommended and bendamustine plus R is a potent therapeutic option. In
      relapsed/refractory FL, re-biopsy is needed to evaluate the possible histological
      transformation to diffuse large B-cell lymphoma. Relapsed/refractory FL patients
      should be registered in clinical study because the optimal treatment in such
      patients is unconfirmed.

PMID- 24724410
TI  - [Marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue type (MALT
      lymphoma)].
AB  - Extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue
      type (MALT lymphoma) is a B-cell tumor thought to originate from B-lymphocytes
      that are normally present in the marginal zone of lymphoid follicles of the
      lymphoid tissue. About 50% of MALT lymphoma occurs in gastrointestinal tract. The
      majority of patients present with localized disease and indolent clinical
      progression. In localized gastric MALT lymphoma with Helicobacter pylori (HP)
      infection, HP eradication is recommended as first line therapy. In those without
      HP infection and localized non-gastric MALT lymphoma, involved field radiation
      therapy(IFRT) is recommended as first line therapy. Patients in advanced stage
      and salvage setting are managed according to the recommendations for advanced
      follicular lymphoma. The long-term survival rate of MALT lymphoma patients is 80
      90%.

PMID- 24724411
TI  - [Current treatment strategy in mantle cell lymphoma].
AB  - Mantle cell lymphoma (MCL) is a well-recognized lymphoma subtype that accounts
      for about 3-6% of all patients with non-Hodgkin lymphoma. The clinical course of
      MCL ranges from an indolent disease to a rapidly progressive malignancy, with a
      poor prognosis and a median overall survival (OS) of about 3-5 years reported in
      earlier data sets. Recent improvement has been achieved by the successful
      introduction of rituximab and dose-intensified approaches including high-dose
      cytarabine and autologous stem cell transplantation strategies especially in
      younger patients of age less than 66 years. In elderly patients, rituximab
      maintenance therapy after R-CHOP therapy was demonstrated to prolong survival.
      However, with the exception of allogeneic hematopoietic stem cell
      transplantation, current treatment approaches are non-curative, and the
      corresponding survival curves are characterized by a delayed but continuous
      decline and a median survival of 4-6 years. In recent years, new insights into
      the biology of MCL have been obtained which have provided the rationale for the
      development of novel therapeutic strategies. Emerging new drugs such as
      bendamustine, proteasome inhibitors, ibrutinib and others are based on the
      dysregulated control of cell cycle machinery and impaired apoptotic pathways. The
      efficacy of these agents as monotherapy was demonstrated to be comparable to
      conventional chemotherapy in relapsed MCL, and combination strategies are
      currently being investigated in clinical trials.

PMID- 24724412
TI  - [Peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS)].
AB  - Peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS) is a heterogeneous
      category of nodal and extranodal mature T-cell lymphomas. PTCL-NOS is a highly
      aggressive lymphoma, and its prognosis is poorer than those of aggressive B-cell
      lymphoma such as diffuse large B-cell lymphoma(DLBCL). Current standard
      chemotherapies for aggressive B-cell lymphoma, such as CHOP, are the commonly
      used regimens for PTCL-NOS, but their efficacies were insufficient and no
      standard treatment has been established. Role of high dose therapy followed by
      autologous stem cell transplantation has not been established as an initial
      treatment. Several new drugs including monoclonal antibodies and molecular target
      drugs are now under investigation.

PMID- 24724413
TI  - [Angioimmunoblastic T-cell lymphoma].
AB  - Angioimmunoblastic T-cell lymphoma (AITL) is a subtype of nodal peripheral T-cell
      lymphoma associated with aggressive clinical course that affects mostly the
      elderly. Clinical features at diagnosis are characterized by polyclonal
      hypergammaglobulinemia, B-symptoms, and advanced stage. It usually responds to
      anthracycline-based chemotherapy but eventually relapses with a median
      progression free survival of less than 2 years. High dose chemotherapy followed
      by autologous stem cell transplantation is an option for improving prognosis both
      in first-line and in relapsed or refractory settings. Several prospective
      clinical trials are evaluating the role of high dose chemotherapy as a
      consolidation in first-line treatment for T-cell lymphoma including AITL.

PMID- 24724414
TI  - [Extranodal NK/T-cell lymphoma].
AB  - The prognosis of extranodal NK/T-cell lymphoma (ENKL) used to be poor and this
      lymphoma was one of the most difficult lymphoma subtypes to treat. However, in
      recent years, novel treatment strategies have been applied, and the prognosis has
      greatly improved. Simultaneous chemoradiotherapy is currently regarded as the
      standard for nasal ENKL limited at most to neck lymph nodes. For advanced or
      relapsed ENKL. L-Asparaginase containing regimen such as SMILE or AspaMetDex is
      recommended. Hematopoietic stem cell transplantation is also recommended for such
      advanced, relapsed or refractory patients. For all patients with ENKL, fragmented
      Epstein-Barr virus-DNA in blood is a good indicator of tumor burden and can
      predict tumor response and adverse reaction by chemotherapy. By using these
      appropriate strategies, the ENKL is currently recognized as a lymphoma subtype
      with intermediate prognosis. Further studies are thus warranted for this
      particular lymphoma.

PMID- 24724415
TI  - [Adult T cell leukemia-lymphoma (ATL)].
AB  - Adult T-cell leukemia-lymphoma(ATL) is a distinct malignancy of CD4+/CD25+/
      CCR4+/FoxP3+ or - Treg/TH2 cells etiologically associated with human T-cell
      lymphotropic virus type I (HTLV-1). ATL is a single HTLV-1 disease entity with
      diverse molecular features. Also, the clinical features and prognosis are diverse
      leading to subtype-classification into acute, lymphoma, chronic, and smoldering
      types defined by organ involvement, and LDH and calcium values. In case acute,
      lymphoma or unfavorable chronic subtypes (aggressive ATL), and favorable chronic
      or smoldering ATL (indolent ATL), intensive chemotherapy followed by allo-HSCT
      and watchful waiting until disease progression has been recommended, respectively
      in Japan. Several new agent-trials for ATL are ongoing and in preparation,
      including a defucosylated humanized anti-CC chemokine receptor 4 monoclonal
      antibody, IL2-fused with diphtheria toxin, histone deacetylase inhibitors, a
      purine nucleoside phosphorylase inhibitor, a proteasome inhibitor and
      lenalidomide.

PMID- 24724416
TI  - [Treatment of Hodgkin lymphoma].
AB  - Hodgkin lymphoma became to be a curative disease. The standard treatment has been
      established for Hodgkin lymphoma, but its optimization still is explored. Risk
      stratification is critical in terms of optimization. The favorable patients would
      be treated with less toxic regimens. PET results are now used to evaluate the
      treatment response, and recently interim PET has been shown as a good predictor
      of prognosis. Interim PET is now incorporated into the treatment strategy of
      Hodgkin lymphoma in clinical trials. Molecular targeting drugs have been
      developed. Brentuximab vedotin, a kind of antibody drug conjugate, showed
      favorable clinical results for relapsed Hodgkin lymphoma.

PMID- 24724417
TI  - [Immunodeficiency related malignant lymphoma: diagnosis and therapy of AIDS
      related lymphoma].
AB  - AIDS-related lymphoma (ARL) remains a significant burden for specialists in
      HIV/AIDS medicine. Pathological findings of ARL are often non-typical in various
      histological types. Diagnosis of correct histological type of ARL by the skilled
      pathologist is essential. Therapy of patients with ARL is the challenge of
      integrating treatment appropriate for the stage and histological subset of non
      Hodgkin lymphoma. In addition to chemotherapy, essential components of an optimal
      ARL treatment strategy include antiretroviral therapy and prophylaxis for
      opportunistic infections.

PMID- 24724418
TI  - [Novel therapy for malignant lymphoma: adoptive immuno-gene therapy using
      chimeric antigen receptor(CAR)-expressing T lymphocytes].
AB  - Adoptive T-cell therapy using chimeric antigen receptor (CAR) technology is a
      novel approach to cancer immuno-gene therapy. CARs are hybrid proteins consisting
      of target-antigen-specific single-chain antibody fragment fused to intracellular
      T-cell activation domains (CD28 or CD137/CD3 zeta receptor). CAR-expressing
      engineered T lymphocytes can directly recognize and kill tumor cells in an HLA
      independent manner. In the United States, promising results have been obtained in
      the clinical trials of adoptive immuno-gene therapy using CD19-CAR-T lymphocytes
      for the treatment of refractory B-cell malignancies, including chronic
      lymphocytic leukemia (CLL) and acute lymphoblastic leukemia (ALL). In this review
      article, CD19-CAR-T gene therapy for refractory B-cell non-Hodgkin lymphoma is
      discussed.

PMID- 24724419
TI  - [Current status and future perspective in inherited cardiac arrhythmias].
AB  - Some patients with inherited cardiac arrhythmias such as congenital long QT
      syndrome (LQTS), Brugada syndrome, and early repolarization syndrome (ERS) have a
      link to mutations in genes encoding for ion channels or other membrane
      components. The diagnosis and management for inherited cardiac arrhythmias have
      been updated in recently published HRS/EHRA/APHRS Expert Consensus Statement.
      More recently, an exome study or whole genome study by using next generation
      sequencer as well as a genome-wide association study (GWAS) by using a gene array
      have been introduced to identify a new responsible gene or to explore the role of
      common genetic variants (polymorphisms) as a susceptible or modifier gene in
      inherited cardiac arrhythmias.

PMID- 24724420
TI  - [Endocytoscopy in the colorectum].
AB  - Endocytoscopy (EC; Olympus), which involves a contact light microscopy system
      (380- or 450-fold) on the distal tip of a colonoscope, is a novel emerging
      endoscopic system. EC enables prediction of the lesion histology or the depth of
      a cancer by on-site observation of both structural and cytological atypia.
      According to the retrospective analysis of 514 colorectal lesions observed with
      use of EC, the diagnostic accuracy of differentiating neoplastic change was
      96.5%, while that of differentiating massively invasive submucosal cancers was
      96.3%. In this article, we report the usefulness of EC focusing on the EC
      classification which classifies colorectal lesions on the basis of EC findings.

PMID- 24724421
TI  - [The newest epidemiology trend of insomnia].
AB  - Sleep disturbance such as insomnia is one of common complaint among adults in
      developed countries. Insomnia induces sleepiness and drowsiness, resulting in a
      reduction of working efficiency in the daytime. Drivers in the transportation
      system and machine operators could cause serious industrial accidents if they
      have sleep disturbances. Recent studies reported that approximately 20% of
      Japanese population had sleep disturbances. Here we provide a general account of
      sleep disturbance about Japanese population.

PMID- 24724422
TI  - [Relation between dementia and circadian rhythm disturbance].
AB  - Dementia and circadian rhythm disturbance are closely linked. First, dementia
      patient shows circadian rhythm disorders (e.g. insomnia, night wandering, daytime
      sleep). These symptoms are a burden for caregivers. Circadian rhythm disturbance
      of dementia relates ADL and cognitive impairment, and diurnal rhythm disorder of
      blood pressure and body temperature. Some study shows that circadian rhythm
      disorders in dementia are a disturbance of neural network between suprachiasmatic
      nucleus and cerebral white matter, and involvement of both frontal lobes, left
      parietal and occipital cortex, left temporoparietal region. The first-line
      treatment of circadian rhythm disturbance should be non-drug therapy (e.g.
      exercise, bright light exposure, reduce caffeine intake, etc.). If physician
      prescribe drugs, keep the rule of low-dose and short-term and avoid
      benzodiazepines. Atypical antipsychotic drugs like risperidone and some
      antidepressants are useful for treatment of insomnia in dementia. But this usage
      is off-label. So we must well inform to patient and caregiver, and get consent
      about treatment. Second, some study shows circadian rhythm disorder is a risk
      factor of dementia. However, we should discuss that circadian rhythm disturbance
      is "risk factor of dementia" or "prodromal symptom of dementia". If a clinician
      finds circadian rhythm disorder in elderly people, should be examined cognitive
      and ADL function, and careful about that patients have dementia or will develop
      dementia.

PMID- 24724423
TI  - [Effects of four bisphosphonates on macrophage phagocytosis: quantitative
      measurement by flow cytometry using high-fluorescence particles and human
      monocytic cell line THP-1].
AB  - Impairment of macrophage phagocytosis is a major cause of chronic inflammation.
      Bisphosphonates (BPs) are widely used as anti-osteoclastic agents. The effects of
      BPs on monocyte-macrophage lineage cells are being increasingly reported;
      however, the detailed effects of BPs on macrophage phagocytic activity are still
      unclear. We examined the effects of four BPs: clodronate as a non-nitrogen
      containing BP (non-N-BP), and pamidronate, alendronate, and zoledronate as
      nitrogen-containing BP(N-BP), on macrophage phagocytic activity. The uptake of
      high fluorescence-labeled polystyrene beads by the human monocytic cell line THP
      1 was investigated by flow cytometry. All three N-BPs suppressed the phagocytosis
      of macrophages more potently than the non-N-BP, clodronate. Pamidronate and
      zoledronate were more potent than alendronate. BP induced the apoptosis of THP-1.
      Pamidronate and zoledronate induced apoptosis more effectively than clodronate.
      The method described to observe phagocytosis was simple and quantitative, and
      might be useful in screening for the effects of drugs, such as N-BP and non-N-BP,
      on phagocytic activity.

PMID- 24724424
TI  - [Diagnostic ability of ultrasonography for the rotator cuff tear: comparison with
      ultrasonography and MRI findings].
AB  - Ultrasonography (US) is a non-invasive method which can assess not only solid
      tissue organs but also soft tissues such as tendons and nerves. However, it has
      not been fully understood that US is a useful tool for the depiction of
      periarticular structure. We compared the diagnostic accuracies between US and
      magnetic resonance imaging (MRI) in the patients with rotator cuff tear (RCT).
      Seventy patients, who underwent arthroscopic surgery, preoperative US and MRI
      examinations at Gifu University Hospital from January 2010 to April 2013 (49
      male, 21 female, mean age 59.7 +/- 15.9) were included in this study. The
      diagnostic accuracy, sensitivity and specificity of US and MRI were 94.3% and
      94.3%, 95.8% and 97.9%, 90.9% and 84.6%, respectively, when the intraoperative
      finding was regarded as a gold standard. These results suggest that US is useful
      for the diagnosis of RCT as equal as MRI.

PMID- 24724425
TI  - [Relationship between serum hCG and urinary hCG in cases of pregnancy, abortion,
      and hydatidiform mole].
AB  - Human chorionic gonadotropin (hCG) is generally quantified in serum, but spot
      urine samples are also used to assess hCG levels in Japan. The purpose of the
      present study was to elucidate whether urinary hCG can be used clinically as a
      substitute for serum hCG. A total of 189 samples of serum and spot urine were
      collected from patients, including cases of normal pregnancy (NP) -13, abortion
      (AB) -21, extrauterine pregnancy (EP) 25, and hydatidiform mole (MOL) -7, during
      medical treatment and comparisons were made concerning serum and urinary hCG
      levels. The histogram of relative urinary/serum hCG(U-hCG.act/S-hCG) of the
      samples showed a wide distribution of values, but tended to converge to a narrow
      distribution by creatinine correction (U-hCG.cor/S-hCG). U-hCG.cor/S-hCG of the
      AB, EP, and MOL groups decreased 1 day to 14 days or was no earlier than 15 days
      postoperatively compared to preoperatively. The alteration of serum Intact/Total
      tended to be similar to that of U-hCG.cor/S-hCG in clinical course. The presented
      case indicated that U-hCG.act/S-hCG did not correspond to serum hCG levels.
      Because urinary hCG levels are inconsistent depending on whether spot urine is
      concentrated or diluted, the levels of hCG in spot urine do not always correlate
      with serum levels of hCG. Therefore, the data of urinary hCG should be
      interpreted after creatinine correction. Overall, it is recommended to determine
      serum hCG levels rather than creatinine corrected urinary hCG levels, considering
      that the relative urinary/serum hCG was not constant postoperatively.

PMID- 24724426
TI  - [Indicators of glycemic control --hemoglobin A1c (HbA1c), glycated albumin (GA),
      and 1,5-anhydroglucitol (1,5-AG)].
AB  - The clinical goal of diabetes management is a good quality of life that is not
      different from that of a healthy subjects. To fulfill the goal, prevention of
      complications is needed under good glycemic control. Although blood glucose
      measurement is essential for glycemic control, there are diurnal variations in
      blood glucose levels. An indicator of long-term glycemic control is necessary.
      HbA1c is the gold standard measurement for the assessment of glycemic control,
      and worldwide large scale clinical studies of diabetes complications have greatly
      valued HbA1c as an indicator of glycemic control. In addition, recently, HbA1c
      was recommended for use in the diagnosis of diabetes in Japan and in the United
      States. Although HbA1c is used widely and internationally, international
      standardization of the HbA1c value has not been achieved. In Japan, from April
      2014, it has been decided to adopt the National Glycohemoglobin Standardization
      Program (NGSP) value, which is used by many countries globally, as the first step
      toward internationalization. Recently, cardiovascular disease in diabetic
      patients has been increasing in Japan. Relationships between postprandial
      hyperglycemia and cardiovascular disease have been noted. Therefore, the
      correction of postprandial hyperglycemia is one of the important goals of
      glycemic control to prevent cardiovascular disease. HbA1c or glycated albumin
      (GA) results from the glycation of hemoglobin or serum albumin and represents 2
      month or 2-week glycemia, respectively. In addition, the glycation speed of GA is
      ten times faster than HbA1c, so GA is likely to reflect the variation in blood
      glucose and postprandial hyperglycemia in combination with HbA1c and its value.
      1,5-anhydroglucitol (AG) is a marker of glycemia-induced glycosuria, since
      reabsorption of filtered 1,5-AG in the proximal tubule is competitively inhibited
      by glucose. It is an indicator to identify rapid changes in hyperglycemia.
      Understanding the characteristics of the indicators above, it is important to use
      them suitably for each diabetes subject and to recognize glycemic control
      conditions more accurately.

PMID- 24724427
TI  - [Continuous glucose monitoring (CGM)].
AB  - Self-monitoring of blood glucose (SMBG) is now commonly used as a tool to measure
      blood glucose levels of diabetic patients, as health insurance started to cover
      its cost for patients receiving insulin. However, SMBG is used to evaluate blood
      glucose levels at different time points, making it impossible to speculate on
      changes in blood glucose levels occurring before and after measurement.
      Currently, continuous glucose monitoring (CGM), which determines diurnal blood
      glucose patterns on a continuous basis, is being introduced into routine clinical
      diabetic care. CGM results sometimes show abnormal blood glucose variations or
      hypoglycemia after meals or during sleep, even if SMBG results show normal levels
      in the same patient. The identification of blood glucose variations is the main
      advantage of CGM. This study reviewed the characteristic of and methods for
      preventing hypo and hyperglycemia based on the pattern of blood glucose
      variations in type 1 and type 2 diabetes that was identified by the introduction
      of CGM.

PMID- 24724428
TI  - [Thyroid disease caused by receptor abnormality].
AB  - Hormone receptor abnormality is a syndrome of an abnormal mechanism caused by
      defective receptor function in hormone action. Resistance to thyroid hormone is a
      syndrome in which the responsiveness of the target organ to thyroid hormone is
      reduced. Resistance to thyroid hormone exhibits unsuppressed thyrotropin(TSH)
      despite elevated free thyroxin (FT4) and free 3,5,3'-triiodothyronine (FT3),
      termed the syndrome of the inappropriate secretion of TSH (SITSH). Resistance to
      thyroid hormone is mainly caused by a mutation in the thyroid hormone receptor
      beta (TRbeta) gene. Genetic analysis of the TRbeta gene is important to diagnose
      resistance to thyroid hormone. TSH receptor (TSHR) abnormality is classified as a
      gain-of-function mutation and loss-of-function mutation. Loss-of-function
      mutations in the TSHR gene occur as TSH resistance, which is found to have
      euthyroid hyperthyrotropinemia or hypothyroidism because of the reduced
      responsiveness of the receptor to TSH. R450H mutation in the TSHR gene is
      occasionally observed in Japanese patients with TSH resistance. In Japan, it is
      suggested that analysis of the R450H mutation in the TSHR gene is useful to
      determine the cause of hyperthyrotropinemia or hypothyroidism.

PMID- 24724429
TI  - [Thyroid ultrasonography--considerations and progress in routine diagnostic
      examinations].
AB  - Thyroid ultrasonography is becoming increasingly important because it is easy to
      perform non-invasively and provides much more information than other imaging
      devices such as CT and MRI. It is possible to infer the causes of diffuse goiter
      and thyrotoxicosis by the internal echo level and blood flow analysis. The
      combination of B mode and color Doppler imaging is also useful for the diagnosis
      of thyroid nodules. Malignant B mode findings include an irregular shape,
      indistinct border, hypo and inhomogeneous internal echo, and fine calcification.
      New diagnostic criteria for thyroid nodules and a flow chart for the selection of
      indications of aspiration biopsy cytology have been developed by the Japan
      Association of Breast and Thyroid Sonology. Recent improvements in thyroid
      ultrasonography include 3D imaging, contrast agents and tissue elasticity
      imaging. 3D ultrasonography and contrast agents have made it possible to display
      vascular structures more accurately. Tissue elasticity imaging is expected to
      play an important role in the diagnosis of thyroid carcinomas since it evaluates
      tissue stiffness objectively. Tissue elastography may be useful for the
      differentiation of follicular adenomas from follicular carcinomas, which is still
      one of the most difficult clinical challenges for all endocrinologists. It also
      provides detailed information on the efficacy of thyroid interventions. New
      combinations with tissue elastography and other imaging devices are under
      development.

PMID- 24724430
TI  - [Future aspect of cytogenetics using chromosomal microarray testing].
AB  - With the advent of chromosomal microarray testing, microdeletions can be detected
      in approximately 17% of cases without any abnormality detectable by conventional
      karyotyping. Structural abnormalities frequently occur at the terminal regions of
      the chromosomes, called the subtelomeres, because of their structural features.
      Subtelomere deletions and unbalanced translocations between chromosomes are
      frequently observed. However, most microdeletions observed by chromosomal
      microarray testing are microdeletions in intermediate regions. Submicroscopic
      duplications reciprocal to the deletions seen in the microdeletion syndromes,
      such as the 16p11.2 region, have been revealed. Discovery of multi-hit
      chromosomal abnormalities is another achievement by chromosomal microarray
      testing. Chromosomal microarray testing can determine the ranges of chromosomal
      structural abnormalities at a DNA level. Thus, the effects of a specific gene
      deletion on symptoms can be revealed by comparing multiple patients with slightly
      different chromosomal deletions in the same region (genotype/phenotype
      correlation). Chromosomal microarray testing comprehensively determines the
      genomic copy number, but reveals no secondary structure, requiring verification
      by cytogenetics using FISH. To interpret the results, familial or benign copy
      number variations (CNV) should be taken into consideration. An appropriate system
      should be constructed to provide opportunities of chromosomal microarray testing
      for patients who need this examination and to facilitate the use of results for
      medical practice.

PMID- 24724431
TI  - [Future direction of pharmacogenomics: identification of genes associated with
      risk of adverse drug reactions using genome-wide association study].
AB  - Drug-induced skin rash characterized by an acute inflammatory reaction of skin
      and mucous membranes is dose-independent, unpredictable, and sometimes life
      threatening. In recent years, the U.S. Food and Drug Administration (FDA) has
      recommended genotyping of polymorphisms in the human leukocyte antigen (HLA)
      prior to drug administration for the avoidance of severe skin rash induced by
      drugs, such as abacavir and carbamazepine. A genome-wide association study (GWAS)
      is useful for the identification of genomic biomarkers that can predict the
      efficacy or risk of toxicity of various drugs. We identified novel susceptibility
      loci associated with the risk of a skin rash induced by nevirapine and
      carbamazepine in Thai and Japanese populations, respectively, through case
      control GWAS with high-throughput single-nucleotide polymorphism (SNP) genotyping
      technology. In order to apply the genomic biomarkers to clinical therapeutics,
      prospective clinical trials will be necessary for the evaluation of an
      intervention based on genetic tests.

PMID- 24724432
TI  - [Evidence-based practice for perioperative patient safety: preface and comments].
AB  - Various kinds of evidence-based checklists and guidelines aimed at patient safety
      in the perioperative period are becoming popular in the clinical setting. These
      include WHO guidelines on surgical patient safety, surgical-crisis checklists,
      checklist for preventing major complications associated with cesarean delivery,
      NICE guidelines for surgical site infection, guidelines for the diagnosis,
      treatment and prevention of pulmonary thromboembolism and deep vein thrombosis,
      appropriateness criteria for stress echocardiography and so on. Better knowledge
      of evidence of these guidelines and check lists for acute care in the
      perioperative period helps us provide high-quality care for surgical patients.
      When we use the guidelines and checklists correctly, we could see what is
      happening in a patient and what to do next for the patient leading us to correct
      diagnosis and appropriate treatment. Thus, evidence-based practice will be
      established in the near future in the perioperative period.

PMID- 24724433
TI  - [WHO Surgical Safety Checklist and guideline for safe surgery 2009].
AB  - The World Health Organization (WHO) launched the Safe Surgery Saves Lives
      campaign in 2007 to improve safety of surgical care in the world. As a part of
      the campaign, the first edition of the Surgical Safety Checklist was created
      through an international consultative process in 2008 and the second edition was
      published in the WHO Guidelines for Safe Surgery 2009. The guidelines consist of
      ten essential objectives for safe surgery, and nine of the ten objectives are
      facilitated by introducing the surgical checklist in the operating room, which is
      designed to improve teamwork of the operating room member and to give them
      chances to use the safety processes consistently. It consists of nineteen check
      points scheduled to be used in three phases: before anesthesia induction, before
      any skin incision, and at the end of surgery. In this article we gave an outline
      of WHO Surgical Safety Checklist and WHO Guidelines for Safe Surgery 2009, and
      reviewed the evidence of the guidelines and checklist. Finally we presented the
      evidence indicating the efficacy of the WHO Surgical Safety Checklist, which
      included the pilot study attached in the guidelines showing that its use markedly
      decreased complications in patients undergoing noncardiac surgery in eight
      diverse international hospitals.

PMID- 24724434
TI  - [Does Surgical Safety Checklist for cesarean section improve maternal and
      neonatal outcome?].
AB  - Surgical Safety Checklist published by WHO (World Health Organization) has been
      widely accepted and contributed to reduce postoperative mortality and morbidity.
      However, the implementation of the original checklist for cesarean section has
      been questioned as most of the patients for cesarean section being awake at the
      occasion of time out, and some patients requiring emergency cesarean section.
      From these points of view, modified versions of the checklist for cesarean
      section have been proposed. Recently, NPSA (National Patient Safety Agency) and
      RCOG (Royal College of Obstetricians and Gynaecologists) from U. K. published a
      checklist specifically for obstetric surgery, and its usefulness has been
      evaluated. The most important modification of the checklist seems to be adoption
      of classification of urgency of cesarean section by NICE (National Institute of
      Clinical Excellence) into the time out Surgical Safety Checklist from U. K. is
      introduced with its recent evaluation, and its possible adoption in Japanese
      hospitals will be discussed.

PMID- 24724435
TI  - [Intraoperative crisis and surgical Apgar score].
AB  - Intraoperative crisis is an inevitable event to anesthesiologists. The crisis
      requires effective and coordinated management once it happened but it is
      difficult to manage the crises properly under extreme stressful situation.
      Recently, it is reported that the use of surgical crisis checklists is associated
      with significant improvement in the management of operating-room crises in a high
      fidelity simulation study. Careful preoperative evaluation, proper intraoperative
      management and using intraoperative crisis checklists will be needed for safer
      perioperative care in the future. Postoperative complication is a serious public
      health problem. It reduces the quality of life of patients and raises medical
      cost. Careful management of surgical patients is required according to their
      postoperative condition for preventing postoperative complications. A 10-point
      surgical Apgar score, calculated from intraoperative estimated blood loss, lowest
      mean arterial pressure, and lowest heart rate, is a simple and available scoring
      system for predicting postoperative complications. It undoubtedly predicts higher
      than average risk of postoperative complications and death within 30 days of
      surgery. Surgical Apgar score is a bridge between proper intraoperative and
      postoperative care. Anesthesiologists should make effort to reduce the
      postoperative complication and this score is a tool for it.

PMID- 24724436
TI  - [Role of anesthesiologist in prevention of perioperative infection].
AB  - Perioprative infection has a significant impact on outcome of surgical patients.
      Anesthesiologists have roles in reducing infection by application of appropriate
      prophylactic measures. Hand hygiene is a prerequisite when contacting patients in
      the operating room. Bundled-preventive approaches should be applied during
      insertion of intravascular lines, specifically central venous lines. Application
      of appropriate skin preparation and/or dressings with antiseptics is important.
      Appropriate selection of antimicrobials depending on surgeries and patients'
      background, and avoidance of periopeative hypothermia are significant preventive
      measures for surgical wound infection. To reduce postoperative pneumonia
      including ventilator-associated pneumonia, avoidance of aspiration during
      intubation process or mechanical ventilation is necessary. Tracheal tube with a
      subglottic secretion drainage port might be applied in patients anticipated to
      receive longer period of postoperative mechanical ventilation and to have a
      greater risk of postoperative pneumonia.

PMID- 24724437
TI  - [Prevention of venous thromboembolism and anticoagulant therapy].
AB  - Perioperative pulmonary thromboembolism (PTE) occurred in 2.93 per 10,000 cases
      and mortality of PTE was 14% in Japan according to the surveillance of Japanese
      Society of Anesthesiologists from 2009 to 2011. Anesthesiologists have to
      evaluate perioperative venous thromboembolism (VTE) risk carefully and take
      adequate measures to prevent PTE. The first step is the assessment of the
      preoperative probability of VTE and the next step is the assessment of the risk
      for VTE during and after operation. If a patient has moderate probability of VTE
      preoperatively, diagnostic procedures are recommended. If the d-dimer is
      positive, whole-leg ultrasound is recommended. If DVT is positive in proximal
      vein, further investigation or anticoagulant therapy are considered. Primary
      preventions of VTE during and after surgeries are as follows. In patients with
      low or moderate risks for VTE, intermittent pneumatic compression is recommended.
      In patients with high risks for VTE, pharmacologic prophylaxes are recommended.
      In recent years newly developed anticoagulants can be available other than low
      dose unfractionated heparin. However, the incidence of VTE in Japanese
      populations is different from western countries. Moreover our own evidence has
      not fully been accumulated yet. Therefore further investigations for prevention
      of perioperative VTE in Japan are expected for our own new guidelines.

PMID- 24724438
TI  - [Perioperative cardiovascular evaluation and management for noncardiac surgery].
AB  - As a population ages, an increase in the number of patients with cardiac
      complications who undergo non-cardiac surgeries is observed. The perioperative
      mortality for noncardiac surgery is approximately 1-5%; approximately 20-35% of
      these cases are due to cardiovascular complications. Among them, perioperative
      myocardiac infarction/ischemia is a factor that leads to poor prognosis, and the
      ACC/AHA guidelines emphasize this aspect. An important task of the
      anesthesiologist is to accurately assess risks in patients undergoing noncardiac
      surgeries and avoid adverse cardiovascular events.

PMID- 24724439
TI  - [Analgesic efficacy and clinical safety of intraperitoneal instillation combined
      with rectus sheath block using ropivacaine for pain relief after laparoscopic
      gynecological surgery].
AB  - BACKGROUND: The aim of this study was to evaluate the analgesic efficacy and
      safety of rectus sheath block combined with intraperitoneal instillation using
      two doses of ropivacaine in patients undergoing laparoscopic gynecological
      surgery. METHODS: Altogether 53 consenting women were randomized to receive
      intraperitoneal infiltration with 0.25% ropivacaine or 0.5% ropivacaine followed
      by rectus sheath block with 0.375% ropivacaine. The outcomes of clinical safety
      were measured using plasma concentration of local anesthetics and occurrence of
      toxic symptoms. The analgesic efficacy was assessed using numerical rating scales
      for pain and morphine consumption up to 24 hours after surgery. RESULTS:
      Patients' baseline characteristics, surgical factors, and analgesic outcomes were
      comparable between the two groups. Although peak plasma concentration of
      ropivacaine was significantly higher in patients receiving 0.5% ropivacaine, none
      of analyzed concentrations was above the toxic ones. Besides, no patients showed
      any symptoms of local anesthetic toxicity. CONCLUSIONS: The present study showed
      that the combination of rectus sheath block with intraperitoneal instillation of
      ropivacaine was safe and potent enough to relieve pain after laparoscopic
      surgery.

PMID- 24724440
TI  - [Retrospective analysis of perioperative cardiovascular complications in patients
      with low left ventricular function undergoing noncardiac surgery].
AB  - BACKGROUND: Regarding patients for noncardiac surgery with low left ventricular
      function, we have little information about perioperative cardiovascular
      complications, making it difficult to evaluate such patients preoperatively and
      to inform them of their perioperative course. METHODS: We retrospectively
      investigated the patients undergoing noncardiac surgery under general anesthesia
      in our hospital from January 2008 to December 2011. The subjects were 52 patients
      with low left ventricular function defined as left ventricular ejection fraction
      under 40%. Patients with perioperative complications were compared with those
      without them in about 14 factors which might influence their perioperative
      course. RESULTS: Only one patient had severe hypotension intraoperatively.
      Postoperatively, five patients had cardiovascular complications in a week and
      three more in a month. Compared with those with complications and those without
      them, significant differences were found in 3 of 14 factors : type of surgery (P
      = 0.006), operation time (P = 0.013), and amount of intraoperative transfusion (P
      = 0.039). CONCLUSIONS: Regarding patients for noncardiac surgery with low left
      ventricular function, high risk of perioperative cardiovascular complications was
      found in a surgery which is highly invasive, long lasting, or requiring massive
      transfusion.

PMID- 24724441
TI  - [Incidence and risk factors of postoperative emergency treatment in dialysis
      patients after elective noncardiac surgery: a five-year retrospective study].
AB  - BACKGROUND: Chronic hemodialysis patients undergoing surgery require intensive
      care. The purpose of this study was to determine the incidence and risk factors
      of emergency treatment before the planned elective postoperative dialysis.
      METHODS: One hundred and ten dialysis patients undergoing elective noncardiac
      surgery were retrospectively analyzed. RESULTS: Emergency treatment was performed
      in 31 (28.1%) of the 110 patients, including one patient with emergency dialysis,
      because of hyperkalemia (n = 27) or metabolic acidosis (n = 4). Receiving
      operating characteristic curve analysis showed a cutoff value for serum potassium
      concentration < 4.0 mEq x l(-1) estimated by maximizing the Youden index. We
      could not find other perioperative data as significant risk factors for emergency
      treatment. CONCLUSIONS: About 30 percent of dialysis patients aftet elective
      noncardiac surgery required emergency treatment. The highest risk was high serum
      potassium concentrations after induction of anesthesia Preoperative serum
      potassium concentrations should be kept below 4.0 mEq x l(-1) to avoid
      postoperative emergency treatment.

PMID- 24724442
TI  - [Reversal of rocuronium-induced neuromuscular blockade with sugammadex in
      patients for cesarean delivery treated with magnesium sulfate].
AB  - BACKGROUND: We investigated whether sugammadex could reverse neuromuscular
      blockade induced by rocuronium in patients for cesarean delivery treated with
      magnesium sulfate preoperatively. METHODS: Twenty-three pregnant women received
      general anesthesia induced with thiopental and rocuronium. They were maintained
      by nitrous oxide, oxygen and sevoflurane (GOS) before delivery and after delivery
      by GOS, midazolam, and propofol. After the surgery, the patients with two or more
      counts of train-of-four (TOF), the moderate block group were classified into Mg (
      ) M and Mg (+) M, depending whether magnesium sulfate had been injected or not,
      and sugammadex 2 mg x kg(-1) was administered to both groups. Patients with PTC 2
      or more, the profound block group, were classified into Mg (-) P or Mg (+) P and
      sugammadex 4 mg x kg(-1) was administered to both groups. Recovery time was
      defined as the time required to reach TOFR 0.9 or more after the injection of
      sugammadex. RESULTS: Median recovery times of the Mg (-) M, the Mg (-) P, the Mg
      (+) M and the Mg (+) P were 63 seconds (range: 26-130, N = 7), 127 seconds
      (range: 63-228, N = 7), 104 seconds (range: 67-133, N = 5), and 142 seconds
      (range: 57-209, N = 4), respectively. CONCLUSIONS: Sugammadex could reverse
      rocuronium-induced neuromuscular blockade in a dose-response manner even in the
      patients treated with magnesium sulfate.

PMID- 24724443
TI  - [Effects of magnesium on the onset time of rocuronium in patients for cesarean
      delivery].
AB  - BACKGROUND: Although magnesium can potentially shorten onset time of a muscle
      relaxant, it is unclear whether it does shorten the onset time of rocuronium for
      patients in cesarean delivery (CD). Thus the purpose of this study is to compare
      the onset time of rocuronium in patients with or without preoperative magnesium
      treatment. METHODS: In 9 CD patients without magnesium (CD group) and 8 CD
      patients with magnesium (CD-Mg group), neuromuscular function was continuously
      assessed with acceleromyography immediately after induction of general anesthesia
      with intravenous injection of thiopental (4-5 mg x kg(-1)) and rocuronium (0.6 mg
      x kg(-1)). Onset time of muscle relaxation, defined by the time from rocuronium
      bolus injection until complete absence of twitch height, was measured. RESULTS:
      The onset time of both groups did not significantly differ (50 +/- 10 seconds vs.
      51 +/- 11 seconds; P = 0.93, unpaired t-test). Median magnesium concentration,
      5.2 mg x dl(-1) (3.8-6.3), and the onset time of CD-Mg group did not correlate
      magnesium concentrations (P = 0.23, Pearson's correlation coefficient test).
      CONCLUSIONS: Magnesium did not shorten the onset time of rocuronium 0.6 mg x kg(
      1) in CD patients.

PMID- 24724444
TI  - [Effects of pregnancy on the onset time of rocuronium].
AB  - BACKGROUND: Rapid onset of a muscle relaxant is required for general anesthesia
      with rapid sequence induction technique. Although a high dose of rocuronium was
      demonstrated to achieve the rapid onset in non-pregnant persons, it is still
      unknown whether this is true in women during late pregnancy. The purpose of this
      study is to compare the onset time of high dose rocuronium between pregnant and
      non-pregnant women. METHODS: Ten pregnant women undergoing cesarean delivery and
      10 age, height, and body weight-matched non-pregnant women were enrolled in the
      study. Neuromuscular function was continuously assessed by twitch response with
      acceleromyography immediately after induction of general anesthesia with
      intravenous injection of thiopental (4-5 mg x kg(-1)) and rocuronium (0.9 mg x
      kg(-1)). Onset time of muscle relaxation, defined by the time from rocuronium
      bolus injection to complete absence of twitch height, was measured. RESULTS: The
      onset time of rocuronium in pregnant women was significantly shorter than that in
      non-pregnant women (42 +/- 9 seconds vs. 56 +/- 10 seconds; P = 0.0039. unpaired
      t-test). CONCLUSIONS: The onset time of high dose of rocuronium in pregnant women
      was significantly shorter than that of non-pregnant women.

PMID- 24724445
TI  - [Plasma levels of anti-oxidant markers during general anesthesia--a comparison
      between remifentanil- and epidural-based anesthesia].
AB  - BACKGROUND: Anesthesia may influence oxidative stress responses to surgical
      stress during surgery. We performed a prospective study to investigate the impact
      of anesthesia on oxidative stress responses between patients receiving
      ropivacaine-based epidural anesthesia and patients receiving remifentanil-based
      general anesthesia METHODS: Plasma levels of oxidative stress-related substances
      such as superoxide dismutase (SOD) and myeloperoxidase were measured during
      anesthesia in patients receiving ropivacaine-based epidural anesthesia (E group)
      and patients receiving remifentanil-based general anesthesia (R group). RESULTS:
      SOD, which catalyzes the reduction of superoxide anions to hydrogen peroxide and
      has anti-oxidative effects, was significantly lower in E group at the end of
      surgery whereas the levels of myeloperoxydase were not different between the
      groups. Plasma levels of adrenaline and noradrenaline were significantly higher
      in R group than E groups after surgery. CONCLUSIONS: Although activation of
      sympathetic nervous system was effectively inhibited by epidural anesthesia. SOD
      level was low in E group. Remifentanil might directly increase SOD, independent
      of sympathetic nervous system.

PMID- 24724446
TI  - [Diagnosis and evaluation of a patient with cor triatriatum using perioperative
      transesophageal echocardiography].
AB  - Cor triatriatum is a rare congenital cardiac anomaly accounting for only 0.1-0.4%
      of all congenital heart diseases usually diagnosed in infancy or childhood and
      rarely found in adults. It is characterized by fibromuscular membrane dividing
      the left atrium into two chambers. This congenital heart disease is reported to
      be frequently associated with variety of cardiac anomalies such as an atrial
      septal defect, anomalous pulmonary venous drainage, and persistent left superior
      vena cava. A woman with no cardiac history was admitted to the hospital due to
      acute heart failure and diagnosed as severe mitral regurgitation and cor
      triatriatum by pre-orerative transthoracic echocardiography. Emergency mitral
      valve plasty was undertaken because of the severity of mitral regurgitation
      without determining the detailed type of cor triatriatum. Thus, diagnosis of the
      type of cor triatriatum with perioperative transesophageal echocardiography (TEE)
      was required to establish correct cardiopulmonary bypass and determine the
      operative procedure. Perioperative TEE revealed that the type was Lucas-Schmidt-
      I A, and cardiopulmonary bypass was established safely. Operation was performed
      without any problems. The TEE skill of our anesthesiologists could contribute to
      the safe management of the cardiac surgery.

PMID- 24724447
TI  - [Intraoperative asystole in a patient with concealed sick sinus syndrome: a case
      report].
AB  - We report a patient with concealed sick sinus syndrome who developed
      intraoperative bradycardia and asystole. An 81-year-old man was scheduled to
      undergo total gastrectomy under general and epidural anesthesia. There was no
      history of syncope, and preoperative 12-lead ECG showed normal sinus rhythm.
      Anesthesia was induced with propofol and remifentanil, maintained with
      sevoflurane, remifentanil and thoracic epidural infusion of lidocaine, fentanyl
      and levobupivacaine. Bradycardia was detected on ECG 110 minutes after the start
      of surgery. Intravenous atropine (0.5 mg, repeated up to a total dose of 1.5 mg)
      was ineffective in restoring a normal heart rhythm. Ten minutes later, the ECG
      changed to asystole lasting for about 15 seconds. Regular chest compression and
      intravenous administration of dopamine (5 microg x kg(-1) x min(-1)) resulted in
      successful recovery of sinus rhythm. Postoperative ECG showed sinus rhythm. The
      final diagnosis by a cardiologist was concealed sick sinus syndrome. Many
      anesthetic agents have some effects on the cardiac conduction system.
      Remifentanil may have played a role in the development of asystole in this
      patient. The existence of concealed sick sinus syndrome should be kept in mind
      even in patients who show no clinical abnormalities on preoperative assessment.

PMID- 24724448
TI  - [Anesthetic management of a patient with moyamoya disease undergoing mitral valve
      repair].
AB  - Moyamoya disease is the result of progressive steno-occlusive changes in the
      internal carotid arteries followed by formation of bilateral abnormal vascular
      networks. The disease may present with cerebral ischemia causing cerebral
      hemorrhage in the perioperative period. There are few reports of cardiac
      surgeries in patients with moyamoya disease, and the management during
      cardiopulmonary bypass for moyamoya disease has not been established. We gave
      general anesthesia for mitral valve plasty in patient with the moyamoya disease.
      A 52-year-old woman underwent mitral valve plasty. She had been diagnosed with
      moyamoya disease and during the cardiopulmonary bypass, we used alpha-stat blood
      gas management with mild hypothermia, and maintained PaCO2 around 40 mmHg. We
      maintained the perfusion flow of CPB above 3.0 l x min(-1) x m(-2) and the mean
      perfusion pressure above 70 mmHg. In addition, we used the pulsatile perfusion
      assist with intraaortic balloon pumping to maintain cerebral circulation.
      Postoperative course was uneventful without apparent neurologic deficit, and she
      was discharged from hospital on 10th postoperative day.

PMID- 24724449
TI  - [Recipient of living kidney transplantation during which heparin-induced
      thrombocytopenia (HIT) was suspected: a case report].
AB  - A 67-year-old woman with a diabetic renal failure was scheduled for a living
      kidney transplantation. Heparin was first used during hemodialysis 5 days before
      operation. Thrombocytopenia was found immediately after induction of general
      anesthesia, and the diagnosis of HIT was wade based on clinical symptom and 4 T's
      scoring. The surgery was continued because of the progress of donor surgery.
      Argatoroban was administered based on APTT measurement as an anticoagulation
      therapy during and after the operation. Although deep vein thrombosis was found
      13 days after the operation, the transplanted kidney was established
      successfully. It is necessary to take a great caution in HIT development after
      heparin use.

PMID- 24724450
TI  - [Case of brain death liver transplantation suspended because of respiratory
      failure after admission to the operating room].
AB  - We experienced a case in which brain death liver transplantation was suspended
      after admission to the operating room because the impaired oxygenation was
      aggravated. A 32-year-old man (weight 70 kg, height 164 cm) who had previously
      undergone living donor liver transplantation for Budd-Chiari syndrome developed
      hepatic failure 11 months after the transplantation and was enrolled in the
      waiting list for brain death liver transplantation. Mechanical ventilation and
      blood purification therapy were performed in the intensive care unit because he
      was in coma and his respiratory function had gradually worsened. A brain-dead
      donor was identified 21 days after enrollment. The patient was transported to the
      operating room when the donor liver arrived at our hospital. However, the surgery
      was suspended because his respiratory function deteriorated further after
      induction of general anesthesia. A patient enrolled in the brain death
      transplantation list often has to wait long for a donor organ. Anesthesiologists
      should actively participate in the preoperative management and evaluation of a
      patient's general status during the waiting period.

PMID- 24724451
TI  - [Case of spinal epidural abscess after continuous epidural block to manage the
      pain of herpes zoster].
AB  - A woman in her 90's received continuous epidural block for the pain of herpes
      zoster. Four days after epidural catheterization, she was found with cellutitis.
      Fourteen days after epidural catheterization, spinal epidural abscess was pointed
      out on MRI. Since there were no neurological symptoms, we performed conservative
      medical management with antibiotics. She recovered without sequela When the
      symptoms of cellutitis appeared after epidural block (even if there are neither
      neurological symptoms nor infectious signs), there is a possibility of
      progressing into spinal epidural abscess.

PMID- 24724452
TI  - [New use of pulse-oximeter as a prophylactic Stimulator to the wearer and a
      lifesaving tools for prevention of hypoxic mishaps].
AB  - Pulse-oximeter has been widely used for the clinical assessment of physical
      status of a patient and as an alarming tool of hypoxia to medical personnel at
      the bedside or in the observation center. However, it has never been used for
      direct stimulation of the wearer. We considered innovation of pulse-oximeter as a
      prophylactic alarm-oximeter for the wearer. If SPO2 goes down to unfavorable
      level, the alarm-oximeter starts to send signal through a control box to a
      stimulator, such as an electrical nerve stimulator, a cold thermal tip, or
      mechanical device like a vibrator or compressor. The dermal stimulator is usually
      fixed to the right or left wrist with a Velcro band. The control box is affixed
      to the wristband by using Velcro. The alarm may be sent to an earphone or speaker
      with a verbal command like "take a deep breath". Alarm-oximeter will be combined
      to an oxygen inhaler or mechanical ventilatory assist device, or a drug
      administration system through electric line or wireless transmitter to start or
      change its function before the arrival of medical personnel. It will prevent
      hypoxic mishaps during medical intervention or sleep apnea syndrome. It will be
      also applicable to stop snoring.

PMID- 24724453
TI  - [Endophenotypes of severe depression].
AB  - Patients with the same diagnosis may present a highly different symptom picture.
      The concept of endophenotype has been created to facilitate the assessment of
      factors underlying psychiatric diseases. The concept allows the reduction of
      heterogenous categories of psychiatric diagnoses into less complicated components
      so that use is made of e.g. neuroanatomy, neurocognitive tests, biochemical
      factors or neuropsychology. Possible endophenotypes of severe depression include
      neurocognitive parameters associated with learning and memory, hippocampal volume
      as well as neuroticism, for example.

PMID- 24724454
TI  - [Radio frequency ablation of Barrett's esophagus--can the risk of esophageal
      adenocarcinoma be reduced?].
AB  - Barrett's esophagus occurs in a little less than 2% of the population. Of the
      patients, very few develop esophageal adenocarcinoma, and on the other hand only
      a small part of esophageal adenocarcinoma patients are diagnosed with Barrett's
      lesion. If Barrett's lesion has a separate visible elevated or depressed lesion
      it should first be treated with endoscopic mucosal resection, and thereafter the
      remaining Barrett's lesion should be destructed by a new technique called
      radiofrequency ablation, RFA. After destruction of the aberrant mucosal lesion
      with RFA it will be replaced with normal esophageal mucosa and the risk for
      malignant trasformation is dimished near to zero. RFA is considered the first
      line treatment treatment option of dysplastic Barrett's esophagus.

PMID- 24724455
TI  - [Treatment of esophageal cancer].
AB  - Treatment of choice for esophageal cancer requires multidisciplinary
      collaboration and requires careful assessment of the stage of the tumor and the
      patient's condition. When the cancer has extended or if the patient will not
      tolerate burdensome treatments, the possibilities of oncological therapies must
      be evaluated. The ability to eat must be secured and the quality of life
      optimized by using palliative means. Surgery still plays a central role in
      striving for curative treatment. Surgical techniques and results have improved,
      and the five-year life expectancy of patients having undergone surgery is over
      40%.

PMID- 24724456
TI  - [Radioiodine in the treatment of generalized papillary and follicular thyroid
      carcinoma].
AB  - Iodine has a physiological function as part of thyroxine, its utilization being
      small elsewhere in the body. In fact, radioiodine can be termed as targeted
      therapy of papillary and follicular thyroid carcinoma. It is an effective means
      of destroying the healthy thyroid tissue remaining after thyroidectomy and thus
      sensitizing the monitoring with serum thyreoglobulin. Radioiodine has maintained
      its status especially in the treatment of locally spread and metastasized thyroid
      carcinoma. Treatment is individualized owing to the varying ability of metastases
      to pick up radioiodine.

PMID- 24724457
TI  - [Oral, pharyngeal and neck infections in specialized care].
AB  - BACKGROUND, MATERIAL AND METHODS: All cases of acute dental, oral and pharyngeal
      infections that were referred to Mikkeli Central Hospital during a 25-month
      period were retrospectively analyzed. RESULTS: Thirty-nine percent of the total
      of 394 cases needed intravenous antibiotics. Tonsillar infections were most
      prevalent (27%), followed by peritonsillar abscesses (25%) and dental infections
      (20%). Twenty patients (5%) had cervical or submandibular cellulitis or abscess
      requiring immediate surgery and an average 8.5 days of in-patient treatment. The
      most prevalent (45%) bacteriological result was miscellaneous "normal flora".
      CONCLUSIONS: Imminent oropharyngeal infection may require immediate surgery and
      intravenous antibiotics.

PMID- 24724458
TI  - [The many faces of neurosyphilis].
AB  - Syphilis is an infectious disease caused by Treponema pallidum. We describe two
      patients with chronic syphilis causing neurosyphilis. The first had had several
      brain infarctions due to the presence of meningovascular syphilis. Second patient
      suffered from motor and psychiatric symptoms caused by syphilis. The symptoms of
      our patients were alleviated by antibiotic therapy. Recognition of the
      multifaceted symptom picture of syphilis is increasingly important, because the
      occurrence of the disease has increased in our country over the last few decades.
      An early enough treatment can prevent permanent disability of the patient.

PMID- 24724459
TI  - [Update on current care guideline: diagnostics of acute myocardial infarction].
AB  - In a patient with acute chest pain or other symptoms suggestive of acute
      myocardial infarction (MI), a 12-lead electrocardiogram with at least two
      additional leads (V4R and V8), should be immediately recorded and evaluated.
      Telemedicine transmission of prehospital electrocardiograms for diagnostic
      evaluation should be part of regional systems of care. Troponin T and I are the
      recommended biomarkers for MI diagnosis. Implementation of uniform diagnostic
      criteria for acute MI is a prerequisite for high quality epidemiological studies
      and for the development of proper performance indicators to assess quality of
      care.

PMID- 24724460
TI  - [How to recognize neurofibromatosis?].
AB  - Neurofibromatosis 1 is a hereditary symptom predisposing to cancer, affecting
      some 1,500 Finnish people. This systemic disease is most commonly detected
      through cutaneous findings. Although the cutaneous symptoms are harmless, they
      impair the patients' quality of life. The disease is, however, insidious, as the
      complications often become manifested from unexpected organ systems. For example
      cancers originally from nervous systems and severe bone lesions require rapid
      diagnosis and treatment. The healthcare personnel should thus be aware of the
      diagnosis of NF syndrome, and the patients should have sufficient knowledge of
      their disease.

PMID- 24724461
TI  - [New biological drugs in the treatment of inflammatory skin diseases].
AB  - Psoriasis in the only skin disease for which biological drug treatments are in
      use. Three of these are TNFalpha inhibitors and one, ustekinumab, is an inhibitor
      of the interleukins (IL) 12 and 23. The new IL-17 inhibitors have proven to be
      highly efficient, and new low molecular weight drugs such as Janus kinase
      inhibitors and phosphodiesterase 4 inhibitors may provide a competitive oral
      alternative to monoclonal antibodies. No biological drugs are available for
      atopic eczema. The pathogenesis of atopic eczema has, however become more
      precise, providing several interesting therapeutic targets in the future.

PMID- 24724462
TI  - [UV radiation, tanning and DNA damage].
AB  - Excessive exposure to UV radiation is the most significant known risk factor for
      skin cancer. Solarium devices produce UVA radiation that is 5 to 10 times
      stronger than that produced by the sun. All wavelengths of UV radiation cause DNA
      damage to skin cells and cause tanning. Tanning protects skin cells from further
      damage. The DNA damages caused by UVA and UVB radiation, however, differ from
      each other. The protective capacity of tanning caused by UVA radiation seems to
      be lower than that caused by UVB radiation.

PMID- 24724463
TI  - [Basal cell carcinoma, squamous cell carcinoma and premalignant skin lesions--how
      to treat?].
AB  - Increasing exposure to UV radiation is considered the most important etiologic
      factor of nonmelanoma skin cancers. Consequently, exposed areas such as the scalp
      and face, are the primary areas for developing non-melanoma skin cancers. Once a
      patient has presented with one tumor, additional lesions are common. The
      diagnosis is based on typical clinical picture and biopsy or excision for
      histopathological analysis. Various non-surgical treatment options have been
      established. Superficial basal cell carcinoma, superficial carcinoma in situ and
      all actinic keratoses are preferentially treated non-surgically. Most other basal
      cell and squamous cell carcinomas should be surgically removed.

PMID- 24724464
TI  - Interactions between Marek's disease virus Rispens/CVI988 vaccine strain and
      adenovirus field strain in chicken embryo fibroblast (CEF) cultures.
AB  - The aim of the study was to determine the influence of adenovirus infection on
      the replication of Marek's disease virus vaccine strain Rispens/CVI988 during in
      vitro co-infection studies. Adenovirus field strain JN-5/10j was isolated from
      sick chickens. The study was conducted in chicken embryo fibroblast cultures
      (CEF). Monolayers of CEFs were infected with Rispens strain and field adenovirus
      strain JN-5/10j with different doses (10(1.0)-10(3.0) TCID50) in the following
      manner: a) simultaneously, b) first, infection with Rispens strain and after 24 h
      infection with adenovirus strain JN-5/10j and c) infection with adenovirus strain
      JN-5/10j 24 h before infection with Rispens strain. After 18, 24, 48, 72, and 96
      h of incubation, the copy number of the pp38 gene of Rispens strain was
      determined using Real-time PCR. The results indicated that the Adenovirus
      infection before the infection with Rispens strain reduced the replication of the
      pp38 gene after 48 h by 2 log10.

PMID- 24724465
TI  - Canine mammary carcinoma cell line are resistant to chemosensitizers: verapamil
      and cyclosporin A.
AB  - Cancer chemotherapy can fail in many ways. One of the most significant is the
      development of multiple drug resistance (MDR), which constitutes a serious
      clinical problem. The development of MDR relates to the expression of a major
      membrane pump, P-glycoprotein (P-gp). Thus, currently one of the goals of
      experimental and clinical oncology is to decrease its activity. So far, many
      different P-gp inhibitors are available, but their efficacy is still questionable
      and requires further study. The aim of our study was to assess an impact of
      classical P-gp inhibitors (verapamil and cyclosporin A) in the reversion of
      multidrug resistance in canine mammary cancer cells. We used two cell lines
      isolated from mammary tumors and two cell lines isolated from their lung
      metastases. All of them showed P-gp over-expression confirmed using Real-time rt
      PCR, Skan(R) screening station and confocal microscopy. The FACS analysis showed
      that in three of the examined cell lines, treatment with verpamil/cyclosporin A
      was ineffective to reverse cancer chemoresistance. However, more studies in this
      field are required.

PMID- 24724466
TI  - Influence of selected stool concentration techniques on the effectiveness of PCR
      examination in Giardia intestinalis diagnostics.
AB  - Giardia intestinalis is a widespread parasitic protozoa which has great
      significance as a public health threat. Molecular diagnostics of stool sample can
      be unreliable because of the presence of inhibitors of enzymatic reactions. The
      aim of this study was to determine the effectiveness of selected pre-treatment
      methods of fecal samples for further PCR-based diagnostics of G. intestinalis,
      and the effect of each component of pre-treatment solutions on PCR reactions.
      Seven stool concentration techniques were compared. The results showed that the
      most efficient concentration method for stool sample preparation for detection of
      G. intestinalis by PCR is centrifugal flotation with Percoll (with saturated
      NaNO3 as the flotation solution). This method is relatively inexpensive, less
      labor-intensive, and suitable for epidemiological monitoring and clinical
      investigations.

PMID- 24724467
TI  - The splenocyte proliferative response and cytokine secretion in mice after 28-day
      oral administration of silver nanocolloid.
AB  - An increasing number of applications of silver nanoparticles in industry,
      medicine and everyday life means that the risk of exposure of the human organism
      to their potential harmful influence is growing. This study has sought to assess
      the effect of 28-day alimentary administration of different concentrations (0.25,
      2.5 and 25 ppm) of a commercial silver nanocolloid on the proliferative activity
      and synthesis of cytokines by mouse splenocytes. All of the analyzed doses of the
      colloid had a significant, albeit different, effect on the activity of
      splenocytes. At the lowest dose, a significant decrease in the proliferation of T
      cells and more intensive synthesis of pro-inflammatory cytokines, both by non
      stimulated and LPS-stimulated cells, was observed. The intermediate dose, on the
      other hand, stimulated proliferation of B cells while producing a pro
      inflammatory effect regarding the synthesis of cytokines. Finally, the highest
      dose decreased the synthesis of cytokines by non-stimulated cells, but after LPS
      stimulation, through the strong activation of the IL-10 synthesis, it raised the
      proliferation of B cells and decreased the synthesis of pro-inflammatory
      cytokines. The results suggest that silver nanoparticles administered orally have
      an easy access to the peripheral organs of the immune system, such as the spleen,
      but the effect of long-term exposure of this organ to the effect of silver
      nanocolloid depends on several factors, including the dose of nanoparticles, and
      seems as difficult to predict.

PMID- 24724468
TI  - The in vitro effect of commercially available noble metal nanocolloids on the
      splenocyte proliferative response and cytokine production in mice.
AB  - Noble metal nanoparticles, currently among the most popular types of
      nanomaterials, are capable of penetrating through biological barriers once they
      enter a living organism. There, they can permeate into organs possessing the
      reticuloendothelial system, such as the spleen. The objective of this study was
      to determine the effect of commercial nanocolloids of noble metals (silver, gold
      and copper), recommended by the manufacturer as dietary supplements, on the in
      vitro viability, proliferative activity and production of cytokines (IL-1beta, IL
      2, IL-6, IL-10 and TNF-alpha) by mouse splenocytes. All of the analyzed colloids
      had some effect on the activity of mouse splenocytes. Silver colloid was
      characterized by high toxicity - concentrations of 1.25 ppm and above
      substantially depressed the viability of cells as well as their proliferative
      activity and ability to synthesize cytokines. The other two colloids were far
      less toxic than nanosilver, although their non-toxic concentrations had a
      significant effect on the production of cytokines by mitogen activated
      splenocytes. The colloid of gold decreased the level of IL-2, and the colloid of
      copper caused an increase in IL-2, IL6 and IL-10. At the same time, copper
      colloid alone induced the synthesis of IL-1beta in mitogen unstimulated cells.
      The results indicate that colloids of noble metals are capable of affecting the
      activity of immunocompetent cells in important peripheral organs of the immune
      system.

PMID- 24724469
TI  - Biochemical and haematological profile of pheasant hens during the laying period.
AB  - The present paper provides new experimental data on the biochemical and
      haematological profile of blood in pheasant hens, and points out the changes in
      both biochemical and haematological parameters that occur during the laying
      period. Significant effects of egg laying on both the biochemical and the
      haematological blood parameters of pheasant hens were found. Biochemical analyses
      revealed a significant increase in the metabolites cholesterol, uric acid,
      lactate, the enzyme aspartate aminotransferase (AST) and the minerals calcium and
      phosphorous, as well as a significant decrease in total protein, albumin and
      glucose in the course of the laying period. Haematological analyses revealed a
      significant increase in the count of leukocytes, lymphocytes, eosinophils,
      basophils and monocytes due to egg laying. In addition, the erythrocyte count and
      haemoglobin content significantly decreased in the middle of the laying period
      and then rebounded at the end of the laying period. The haematocrit content
      gradually decreased till the end of the laying period. All together, the results
      of this study underline the impact of the reproduction status of pheasant hens on
      basic blood parameters. The biochemical and haematological values presented in
      this study may be of help in assessing disease conditions in laying pheasant
      hens.

PMID- 24724470
TI  - Changes in Th1 and Th2 cytokine concentrations in ileal Peyer's patches in gilts
      exposed to zearalenone.
AB  - GALT induces tolerance to foreign food antigens and plays an important role in
      the development of food allergies and the inflammatory bowel disease. The immune
      function of GALT is significantly influenced by an equilibrium between Th1 and
      Th2 subpopulations and the cytokines they produce. Th1 cytokines participate in
      the induction of a cell-mediated immune response, whereas Th2 cytokines induce
      powerful antibody-mediated responses. Changes in Th1/Th2 cell polarization of an
      immune response are associated with susceptibility to autoimmune and infectious
      diseases. This experiment investigated changes in cytokine levels produced by Th1
      and Th2 cells in ileal Payer's patches in gilts exposed to ZEN doses below the
      NOEL (approximately 8 microg kg(-1) BW) for 14, 28 and 42 days. A significant
      linear increase in IL-4 (40.32 +/- 1.55 ng mg(-1)--137.60 +/- 29.96 ng mg(-1)),
      and IL-10 (5.99 +/- 0.15 ng mg(-1)--16.39 +/- 1.11 ng mg(-1)) concentrations was
      observed. An increase in Th1 (IL-2 and IFN-gamma) cytokine levels was also noted
      in the experimental group, but it was not statistically significant. An HPLC
      analysis of Peyer's patches in group E animals revealed a linear increase in ZEN
      concentrations (3.65 +/- 0.91 ng g(-1)--4.72 +/- 1.85 ng g(-1)) and an absence of
      alpha-ZEL. IL-4 stimulates monocytes and macrophages, it induces the production
      of proinflammatory cytokines and it may directly and indirectly contribute to the
      development of inflammatory foci. Higher IL-4 levels could shift polarization
      toward Th2 cells, stimulate B cells to undergo class switching to produce IgE and
      contribute to the development of allergies.

PMID- 24724471
TI  - Alternative for improving gut microbiota: use of Jerusalem artichoke and
      probiotics in diet of weaned piglets.
AB  - The aim of the study was to determine the effect of Jerusalem artichoke and
      probiotics on defence activity of intestinal cells of weaning pigs. One hundred
      eighty piglets (7 weeks old) were fed with basal feed supplemented with Jerusalem
      artichoke, Lactobacillus reuteri and Pediococcus pentosaceus. After 5 weeks, the
      piglets were slaughtered and the gastrointestinal contents and intestine samples
      were taken for analysis. Results demonstrated that in pigs fed basal diet with
      both probiotics and Jerusalem artichoke (5% of basal diet) (T3 group) had less
      (P<0.05) faecal Enterobacteriaceae microorganisms and coliforms and had more
      (P<0,05) faecal Lactobacillus than in pigs from other groups. Increase by 2% of
      Enterobacteriaceae and E. coli levels were seen only in control piglets (T1
      group). E. coli O157 was found at the closing stage in the piglets fed basal diet
      with only Jerusalem artichoke powder (T2 group), but Salmonella enteritidis -
      only in T1 group. In jejunum of T2 group piglets, large deterioration of crypts,
      a moderate inflammation process and plasmocytes were seen, but in jejunum of T3
      group piglets - branching of apical surface of villi, moderate degeneration and
      mitosis of enterocytes were observed. A moderate number of apoptotic cells in T2
      group was found mainly in colon inflammation cells and plasmocytes, but for T3
      group piglets--both in jejunum enterocytes and migrating cells. Our study
      indicated that beta-defensin 2 and 3 expression in jejunum and colon segments
      were incresed in T1 and T2 groups. Findings suggest that feeding with probiotics
      and Jerusalem artichoke significantly improves the microbial contents, defence
      and regeneration processes in the intestine of pigs.

PMID- 24724472
TI  - Phenotypic and genotypic characterization of Bordetella bronchiseptica strains
      isolated from pigs in Poland.
AB  - A total of 209 Bordetella bronchiseptica (Bbr) strains isolated from pigs were
      examined. Phenotypic study included: biochemical characterization (motility,
      catalase, oxidase, urease activity, nitrate reduction and growth on MacConkey
      agar) and antimicrobial susceptibility (disc diffusion method). Genotypic studies
      based on detection of three genes encoded virulence factors, such as: flagella
      (fla), dermonecrotoxin (dnt), and exogenous ferric siderophore receptor (bfrZ),
      using PCR. Most of the Bbr strains tested had a homogeneous biochemical profile.
      97.6% of them provided suitable results in biochemical tests. All Bbr isolates
      tested showed high resistance to penicillin (100%), linco-spectin (100%) and
      ceftiofur (97.9%). Over 57% and 43% of Bbr strains were resistant to ampicillin
      and amoxicillin, respectively. All Bbr isolates showed high sensitivity to most
      chemotherapeutics used such as enrofloxacin (97.9%), tetracycline (97.9%),
      oxytetracycline (97.9%), amoxicillin with clavulonic acid (95.8%), florfenicol
      (90.4%), and gentamicine (77.6%). Over of 94% of Bbr strains were moderately
      susceptible to norfloxacine. Molecular analysis confirmed that almost all
      evaluated Bbr strains (94.7%) possessed the fla gene. A lower percentage of
      isolates had the dnt gene (72.7%) and the lowest percentage of strains (51.7%),
      had the bfrZ gene.

PMID- 24724473
TI  - Detection of Echinococcus multilocularis in faeces by nested PCR with the use of
      diluted DNA samples.
AB  - The aim of this study was to choose the optimal variant of PCR examination of
      faeces to detect Echinococcus multilocularis infection which would allow to
      reduce the influence of different inhibitors in faeces. The investigation was
      carried out by comparison of 3 different methods of DNA isolation from faeces and
      different DNA dilutions used in PCR. Thirty five intestines of red foxes were
      used. Small intestines were examined by the sedimentation and counting technique
      (SCT). Faeces were collected from the rectum for PCR and flotation. DNA were
      isolated with the use of 3 different methods. Two methods were dedicated for
      faeces: method 1 (M1)--for larger samples and method 2 (M2) - for standard
      samples. The third method, method 3 (M3), was not dedicated for faeces. DNA
      samples were tested by nested PCR in 6 variants: not diluted (1/1) and 5 diluted
      (1/2.5, 1/5, 1/10. 1/20, 1/40). E. multilocularis was found by SCT in 18 from 35
      (51.4%) intestines. Taenia-type eggs were detected only in 20.0% of faecal
      samples. In PCR the highest number of positive results (45.7%) were obtained
      during examination of DNA isolated by M1 method, and then 40.0% and 34.3%,
      respectively, for M2 and M3. In some samples positive results in PCR were
      obtained only in diluted DNA. For example, 8 from 12 positive samples isolated by
      M3 method gave the PCR negative results in non-diluted DNA and positive only
      after dilution 1:2.5, 1:10 or 1:20. Also 3 samples isolated by methods dedicated
      for stool gave positive results only after DNA dilution. The investigation has
      revealed that in copro-PCR for detection of E. multilocularis infection
      additional using of diluted DNA (besides non diluted) can avoid false negative
      results causing by PCR inhibition. In the best method of DNA isolation (M1), the
      use of non diluted DNA sample together with diluted in proportion 1:10 seems to
      be optimal.

PMID- 24724474
TI  - Effect of short-term rapid ventricular pacing followed by pacing interruption on
      arterial blood pressure in healthy pigs and pigs with tachycardiomyopathy.
AB  - Ventricular tachycardia may lead to haemodynamic deterioration and, in the case
      of long term persistence, is associated with the development of
      tachycardiomyopathy. The effect of ventricular tachycardia on haemodynamics in
      individuals with tachycardiomyopathy, but being in sinus rhythm has not been
      studied. Rapid ventricular pacing is a model of ventricular tachycardia. The aim
      of this study was to determine the effect of rapid ventricular pacing on blood
      pressure in healthy animals and those with tachycardiomyopathy. A total of 66
      animals were studied: 32 in the control group and 34 in the study group. The
      results of two groups of examinations were compared: the first performed in
      healthy animals (133 examinations) and the second performed in animals paced for
      at least one month (77 examinations). Blood pressure measurements were taken
      during chronic pacing--20 min after onset of general anaesthesia, in baseline
      conditions (20 min after pacing cessation or 20 min after onset of general
      anaesthesia in healthy animals) and immediately after short-term rapid pacing. In
      baseline conditions significantly higher systolic and diastolic blood pressure
      was found in healthy animals than in those with tachycardiomyopathy. During an
      event of rapid ventricular pacing, a significant decrease in systolic and
      diastolic blood pressure was found in both groups of animals. In the group of
      chronically paced animals the blood pressure was lower just after restarting
      ventricular pacing than during chronic pacing. Cardiovascular adaptation to
      ventricular tachycardia develops with the length of its duration. Relapse of
      ventricular tachycardia leads to a blood pressure decrease more pronounced than
      during chronic ventricular pacing.

PMID- 24724475
TI  - Effect of inulin extracts or inulin-containing plant supplement on blood lipid
      indices and fatty acid profile in fattener tissues.
AB  - The objective of the study was to evaluate the effect of inulin or dandelion,
      chicory and Jerusalem artichoke powder on lipid indices and fatty acid profile in
      fattener tissues. The experiment involved 120 crossbred pigs (PL x PLW) x Duroc
      with an initial body weight of 25.0 +/- 0.5 kg. Animals were assigned into 6
      groups. A diet for group I (control) did not comprise an inulin additive, group
      II and III received 2% inulin (water or water-alcohol extraction of inulin from
      chicory root, respectively), while the mixtures for group IV, V and VI contained
      4% root powder from Jerusalem artichoke (topinambur), chicory or dandelion,
      respectively. The animals were slaughtered at 115 kg body weight. The samples of
      blood, liver and the muscle longissimus dorsi tissues as well as whole hearts
      were collected for analysis. Fatty acid profile, some lipid indices and crude fat
      and cholesterol content were evaluated. Dietary supplement of 40 g dandelion
      powder resulted in preferable significant changes in the blood lipid indices and
      fatty acids composition (increased PUFA share and decreased n-6/n-3 ratio).

PMID- 24724476
TI  - Allometric scaling of marbofloxacin pharmacokinetics: a retrospective analysis.
AB  - The association between physiologically dependent pharmacokinetic parameters
      (CL(B), T1/2beta, Vd(ss)) of marbofloxacin and body weight was studied in eight
      animal species based on allometric equation Y = aWb, where 'Y' is the
      pharmacokinetic parameter, 'W' is body weight, 'a' is allometric coefficient
      (intercept) and 'b' is the exponent that describes relation between
      pharmacokinetic parameter and body weight. The body clearance of marbofloxacin
      has shown significant (P < 0.0001) relation with size (Bwt) in various animal
      species. However, half-life and volume of distribution were not in association
      with body weight. Although half-life and volume of distribution were not in a
      good correlation with body weight, statistically significant association between
      the body clearance and body weight suggests validity of allometric scaling for
      predicting pharmacokinetic parameters of marbofloxacin in animal species that
      have not been studied yet. However further study considering large sample size
      and other parameters influencing pharmacokinetics of marbofloxacin is
      recommended.

PMID- 24724477
TI  - Glutathione and glutathione-related enzymes in rats exposed to dimethoate and/or
      pyrantel.
AB  - The study was undertaken to examine the effect of single and combined
      administration of dimethoate (an OP insecticide) and pyrantel embonate (an
      anthelmintic agent) on the concentration of reduced glutathione (GSH) and the
      activity of glutathione peroxidase (GPx) and glutathione reductase (GR) in rats.
      Dimethoate (Group I) was administered to rats at a dose of 1/10 LD50 for 5
      consecutive days and pyrantel embonate (Group II) at a dose of 1/5 LD50 for 3
      consecutive days. The animals of group III were given both of the mentioned above
      compounds in the same manner as group I and II, but pyrantel embonate was applied
      on day 3, 4, and 5 from the beginning of dimethoate intoxication. Material from 6
      rats randomly selected from each group was obtained after 3, 6 and 12 hours and
      2, 7 and 14 days following the last applied dose of the compounds under study. It
      was found that application of pyrantel embonate caused only slight changes in the
      analysed parameters i.e. GSH, GPx and GR. Dimethoate administration caused
      disturbances in the antioxidative system manifested as a decrease in GSH
      concentration in the liver (max.--37.7% after 6 hours) and an increase of GPx and
      GR activities in erythrocytes (max.--21.7% and 29.6% after 3 hours,
      respectively), compared to the control group. The profile of changes after
      combined intoxication was similar, but their intensity was higher compared to the
      group of animals exposed to dimethoate only. Based on current studies, it was
      concluded that both dimethoate and pyrantel embonate at the applied doses showed
      a pro-oxidative activity.

PMID- 24724478
TI  - The effect of dietary L-arginine intake on the level of antibody titer, the
      relative organ weight and colon motility in broilers.
AB  - This study was carried out to determine the effect of L-arginine (L-Arg) levels
      in diet at the starter, grower and finisher phases on immune response, organ
      development, nitric oxide (NO) metabolism and colon motility in broilers. A total
      of 500 one-day-old Ross-308 broiler chickens of mixed sex were separated into one
      Arg-deficient group and four experimental groups. Each group was then divided
      into five subgroups of 20 birds each. Arginine deficient group for all phases was
      fed a basal diet which contained 10% less L-Arg than optimum Arg requirement
      recommended by the breeder. Experimental groups were fed a basal diet
      supplemented with L-Arg which was progressively 10% increased in groups. Thus,
      the diet contained 90, 100, 110, 120 and 130% of optimum Arg requirement for each
      phases in groups, respectively. The highest serum infectious bursal disease
      antibody titer (IBD) was observed in the experimental group which was fed the
      diet containing 110% L-Arg at grower phase (P < 0.05), whereas Newcastle disease
      antibody titer did not differ between groups. The relative weight of spleen
      increased in groups which were fed the diet containing 120 and 130% L-Arg at
      starter phase as compared to Arg-deficient group (P < 0.05). The group which was
      fed the diet containing 110% L-Arg showed highest relative weight of bursa
      Fabricii at grower (P < 0.05) and finisher (P < 0.01) phases. It was observed
      that serum nitric oxide (NO) concentration decreased in Arg-deficient group (P <
      0.05). The amplitude of spontaneous colon contractility did not differ between
      groups at the end of all three phases. However, the frequency of spontaneous
      colon contractility in the Arg deficient group was higher at starter (P<0.05),
      grower (P < 0.01) and finisher (P < 0.05) phases. These results suggest that the
      supplementation of L-Arg at higher level than optimum Arg requirement in broiler
      diet has minimal effect on parameters investigated in the study. However, L-Arg
      deficiency may negatively affect immune response and the motility of
      gastrointestinal system due to disruption of NO metabolism at three phases.

PMID- 24724479
TI  - Effect of vaginal administration of prostaglandin E2 and/or 17beta-estradiol on
      luteal function and histological characteristics of the cervix in cyclic pigs.
AB  - The overall objective of this study was to examine the effect of vaginal
      administration of prostaglandin E2 (PGE2) and/or 17beta-estradiol (E2) on luteal
      function maintenance and histological properties of the porcine cervix. For this
      purpose, crossbred gilts were divided into three groups (n=5 per group) supplied
      on days 11-16 of the estrous cycle with suppositories containing: (1) placebo
      (Group I, Control); (2) 0.4 mg of E2 (Group II); (3) 0.4 mg of E2 and 2 mg of
      PGE2 (Group III). Blood samples were collected on days 11-19 of the estrous cycle
      to determine the concentration of progesterone (P4). Additionally, to examine
      local effects of the hormones applied, segments from the uterine and vaginal
      parts of the cervix and from the ovaries were collected post-mortem. Prolonged
      luteal function and extended synthesis of P4 were observed in 2 of 5 gilts
      receiving PGE2 and E2 simultaneously (Group III). Then, these gilts were
      subdivided into Group IIIA (n = 2; presence of corpora lutea on the ovaries) and
      Group IIIB (n = 3; lack of corpora lutea). Increased levels of plasma P4 were
      observed in Group IIIA on days 15-19 compared to Group IIIB and on days 16-19
      compared to Group I and Group II (P < 0.05; P < 0.01; P < 0.001, respectively).
      In the cervix of gilts in Groups II and III, enlarged blood vessels in the lamina
      propria of both parts of the cervix were observed. Furthermore, in Group II the
      epithelium of the uterine part of the cervix was thicker (P < 0.001). Our study
      confirmed the proposed luteotrophic/antiluteolytic actions of E2 and PGE2 applied
      intravaginally. These results are significant considering that very low doses of
      E2 were used when compared to previous attempts. Despite the inadequate response
      to treatments in some of the gilts, the local effects of these hormones on the
      histological properties of the porcine cervix suggest that further improvements
      in the vaginal administration route might help to elaborate new methods for
      enhancing the luteal function in the pig.

PMID- 24724480
TI  - In vivo inhibitory effect of Aloe vera gel on the ability of mouse parental
      splenic lymphocytes to induce cutaneous angiogenesis in recipient F1 mice.
AB  - Lymphocyte-induced angiogenesis test (LIA) is a model of local graft-versus-host
      (GVH) reaction, marker of the earliest events resulting from activation of donor
      lymphocytes after contact with host semi-allogeneic histocompatibility antigens.
      The effect of in vivo oral administration of Aloe vera gel for 21 days to
      maternal strain (Balb/c) donor mice on the ability of their splenic lymphocytes
      to induce cutaneous angiogenesis (LIA test) in F1 Balb/c x C3H recipients, was
      studied. RESULTS: Neovascular reaction evaluated 72 hours after cells grafting
      was significantly lower in F1 mice grafted with lymphocytes collected from Aloe-
      fed donors, than in recipients of lymphocytes collected from respective controls.
      CONCLUSIONS: This observation opens the promise of safe and ethically acceptable
      possibility of use of Aloe vera gel in human donors in prevention of GVHD in
      recipients of bone marrow grafts.

PMID- 24724481
TI  - Evaluation of reticulated platelets in dogs with breed-related thrombocytopenia.
AB  - The aim of this study was to evaluate the percentage of reticulated platelets in
      healthy dogs with breed-related thrombocytopenia. Seventy two dogs, clinically
      healthy, were enrolled in the study. Blood was collected from the patients and
      anticoagulated with tripotassium ethylenediaminetetraacetic acid (K3-EDTA) and
      sodium citrate. Platelet count was obtained by an impedance haematology analyser
      and platelet morphology was evaluated by examination of blood smears. Patients
      were allocated into two groups. Group 1 consisted of 30 dogs with normal platelet
      count, whereas group 2 was composed of 42 dogs with thrombocytopenia.
      Thrombocytopenia was present in both K3-EDTA and citrate blood samples. Patients
      with thrombocytopenia were divided into two subgroups: the first subgroup
      included dogs with platelet count in K3-EDTA anticoagulated blood from 100 to 200
      x10(9)/L, patients in the second subgroup had a platelet count of less than 100
      x10(9)/L. The percentage of young reticulated platelets (RPs) labelled with
      thiazole orange, and the percentage of platelets coated with platelet surface
      associated IgG, were determined in platelet-rich plasma (PRP) by a flow
      cytometer. The mean percentage of RPs in K3-EDTA and citrate PRP was
      significantly higher in dogs with thrombocytopenia than in dogs with normal
      platelet count. The mean percentage of RPs was significantly higher in citrate
      PRP than in K3-EDTA PRP in all groups. The results suggest that idiopathic,
      asymptomatic thrombocytopenia is not caused by platelet surface-associated IgG.
      Dogs with breed-related thrombocytopenia have a competent bone marrow.

PMID- 24724482
TI  - Serum paraoxonase-1 activity of dairy Holstein-Fresian cows in different
      lactation stages--preliminary study.
AB  - The objective of this study was to investigate paraoxonase-1 (PON-1) activity in
      different lactation stages. The study was conducted on Holstein--Friesian dairy
      cows in 2nd and 3rd lactation. A significant decrease in paraoxonase activity was
      found in the postpartum period and during peak of lactation. Serum triglyceride
      and cholesterol concentration were also markedly reduced during postpartum
      period. The concentrations of uric acid in serum was 23% higher during lactation
      peak in comparison with dry and postpartum period. The results indicate that
      lower serum paraoxonase activity and higher concentration of uric acid are
      associated with oxidative character of transition period and lipid functional
      antioxidative protection during intensive milk production.

PMID- 24724484
TI  - Bone marrow-origin stem/progenitor cells in the mammary gland of heifers.
AB  - The aim of the study was to estimate the size of bone marrow-origin
      stem/progenitor population in 2-year old nonpregnant Holstein-Friesian heifers.
      Quantitative and qualitative analysis was done using scanning cytometry and
      confocal microscopy of mammary tissue slices labelled with the combination of two
      markers: Sca-1 (marker of stem-progenitor cells) and CD45 (marker of
      hematopoietic cells). The average (+/- SEM) percentage of Sca-1POS CD45 POS cells
      was 0.89 +/- 0.21. They were localized mainly outside of mammary ducts, in the
      stroma and sometimes intraluminally. Our results indicate that the subpopulation
      of Sca-1POS cells bearing CD45 antigen may enrich the niche of mammary
      stem/progenitor cells from the bone marrow and participate in the growth of the
      mammary gland in post-pubertal heifers.

PMID- 24724483
TI  - Using of immunocytochemistry in differential diagnosis of neoplasms of serosal
      cavities in dogs.
AB  - The presence of tumor within the serosal cavities, often connected with
      accumulation of serosal effusion, is a quite common problem in the small animal
      veterinary medicine. The first step in diagnosis of such cases is
      cytopathological examination. The aim of the present study was to evaluate the
      usefulness of cytology and immunocytochemistry, using commercially available
      antibodies (anti-cytokeratin, anti-vimentin, and anti-desmin), in differential
      diagnosis of malignant tumors located within serosal cavities in dogs. The final
      cytological diagnosis of carcinoma/adenocarcinoma, sarcoma, and mesothelioma was
      obtained on the basis of routine cytopathology and immunocytochemistry, and then
      confirmed by histopathology and immunohistochemistry. Cytoplasmic
      immunoreactivitiy of normal mesothelid cells and cytoplasmic immunoreactivity of
      hyperplastic mesothelial cells revealed constant and strong expression of all
      examined intermediate filaments: cytokeratin, vimentin and desmin. Application of
      routine cytopathology and immunocytochemistry allowed 32 neoplastic tumors to be
      detected: 19 cases of carcinomas/adenocarcinomas, 6 cases of sarcomas, 7 cases of
      mesotheliomas. Immunostaining of cytopathological samples with chosen set of
      antibodies: anti-cytokeratin, anti-vimentin, anti-desmin is a useful, and low
      invasive test for differentiation between mesotheliomas and
      carcinomas/adenocarcinomas in dogs.

PMID- 24724485
TI  - Serum selenium concentration and glutathione peroxidase activity and selenium
      content in testes of Polish Konik horses from selenium--deficient area in North
      Western Poland.
AB  - The aim of this study was to determine serum selenium concentrations in Polish
      Konik horses residing in the Odra Delta Nature Park (Poland) and to evaluate the
      activity of glutathione peroxidase and Se content in testes of this horse breed.
      In over 95% of cases, serum Se concentration was below the optimal range, and
      none of the horses examined was deficient in this trace element. The lack of Se
      deficiency in the animals examined suggests however, that the Polish Konik horses
      have a natural ability to the optimal use of nutrients available in their life
      area. Testicular content of Se and GSHPx activity in the colts was higher than
      those found in stallions, and a positive relationship between these antioxidants
      was demonstrated. The differences in Se contents and GSHPx activities in testes
      between colts and stallions suggest that selenoenzymes play important roles
      during the puberty of male horses.

PMID- 24724486
TI  - Antimicrobial resistance in bacteria isolated from pigeons in Poland.
AB  - The present study investigated the drug-resistance to the selected antibiotics in
      Escherichia coli, Salmonella typhimurium and beta-haemolytic coagulase-positive
      staphylococci isolated from pigeons bred in Poland. In the case of E. coli,
      tetracyclines and amoxicillin were least effective. In the staphylococci, the
      highest resistance was detected for oxytetracycline and quinolones and 5% were
      resistant to methicillin. The lowest drug-resistance was reported for Salmonella
      typhimurium.

PMID- 24724487
TI  - Association between decreased blood pressure and azotaemia in canine babesiosis.
AB  - Acute tubular necrosis (ATN) was described in canine babesiosis. Hypotension is
      considered as one of the factors which influence the development of hypoxic renal
      damage. In this study hypotension defined as mean arterial pressure (MAP) < 80
      mmHg was detected in 7 out of 48 dogs (14.6%) infected with Babesia canis. Lower
      systolic arterial pressure (SAP), diastolic arterial pressure (DAP) and MAP were
      detected in azotaemic dogs infected with B. canis. Statistically significant
      negative correlations between blood pressures (SAP, DAP and MAP) and serum
      creatinine and urea concentrations showed the influence of decreased blood
      pressure on the development of azotaemia and is probably also associated with ATN
      in canine babesiosis.

PMID- 24724488
TI  - Effect of age and breeding season on sperm acrosin activity in the arctic fox
      (Alopex lagopus L.).
AB  - The objective of this study was to determine the effect of age and reproductive
      season on selected properties of semen from the arctic fox, Aloper lagopus L. The
      experiment used 40 ejaculates collected manually from 6 animals (3 foxes aged one
      year and 3 foxes older than three years). Statistically less semen (0.39 cm3) was
      collected from the young compared to the older animals, and the ejaculates
      obtained were characterized by higher concentration of spermatozoa (195.04 x
      106/cm3). In turn, sperm acrosomal extracts from the older animals contained
      statistically more acrosin (6,4 mU/106 spermatozoa). In the sperm acrosomal
      extracts prepared during the first semen sampling, the mean acrosin activity did
      not exceed 2.3 mU/million spermatozoa. At subsequent semen sampling dates, the
      activity of the analysed enzyme increased to reach 7.72 mU/million spermatozoa.
      In the extracts obtained from the semen collected at the end of the breeding
      season of arctic foxes, the acrosin activity again reached a value obtained at
      the beginning of the season.

PMID- 24724489
TI  - Post-harvest Salmonella spp. prevalence in turkey carcasses in processing plant
      in the northeast part of Poland.
AB  - Turkeys carcasses at selected point after slaughter on dressing line in poultry
      were sampled and analyzed for Salmonella. These slaughter turkeys came from the
      northeast part of Poland. The examinations were carried out in each month of
      2009. Three hundred turkeys were selected at random from a commercial slaughter
      line, immediately after completing the cooling process. The percentage of these
      300 turkeys from which Salmonella spp. were isolated was relatively high (8.3%;
      Salmonella positive results were observed in 25 cases). The lowest Salmonella
      spp. rate (1.3 %) for slaughter birds was found in the fourth quarter, and the
      highest contamination rate at 18.6% was found, in the third quarter. The
      serological types of Salmonella spp. isolated from the whole turkey carcasses
      were S. Saintpaul, S. Senftenberg, S. Anatum, S. Heidelberg, S. Hadar, S.
      Typhimurium and S. Infantis.

PMID- 24724490
TI  - Haemorhagic enterotoxemia by Clostridium perfringens type C and type A in silver
      foxes.
AB  - Type C and type A of C. perfringens were detected in the seat of natural
      infections in silver foxes characterized by symptoms of haemorrhagic
      enterotoxemia. In all of the dead foxes characteristic changes were noted in the
      small intestine and parenchymatous organs. The production of alpha and beta
      toxins by isolated bacteria was confirmed by the bioassay using white mice and by
      PCR. The results of the drug sensitivity testing showed that isolated strains
      were highly susceptible to amoxicillin with clavulanic acid, metronidazole,
      doxycycline and penicillin with streptomycin.

PMID- 24724491
TI  - Is adenomyosis a problem in reproduction and fertility?
AB  - Adenomyosis is defined as the presence of glandular foci beside the endometrium
      of uterus: in the myometrium and/or perimetrium depending on the progress of the
      disorder. So far, adenomyosis has been diagnosed in women and rodents, and
      studies conducted on cows have been rare. In this review we: (1) summarize the
      knowledge regarding adenomyosis, (2) compare the symptoms and aetiopathology
      between women and cows, (3) describe angiogenic uterine processes related to
      adenomyosis development and (4) outline the influence of adenomyosis on proper
      fertility processes in cattle (conception and fertility rates).

PMID- 24724492
TI  - Methods and difficulties in detection of Clostridium botulinum and its toxins.
AB  - The aim of this work was to present selected data regarding traditional and
      modern methods for C. botulinum and its toxins detection. In this article,
      methods based on culturing techniques, mouse bioassay, immunological techniques,
      chromatography and PCR, PFGE, RFLP, AFLP are described. The mentioned techniques
      were evaluated considering their usefulness in the samples examination,
      genotyping of strains and the diagnostics of botulism.

PMID- 24724493
TI  - Pharmacological characteristics of metamizole.
AB  - Metamizole (dipyrone) is a popular analgetic, non-opioid drug, commonly used in
      human and veterinary medicine. In some cases, this agent is still incorrectly
      classified as a non-steroidal anti-inflammatory drug (NSAID). Metamizole is a pro
      drug, which spontaneously breaks down after oral administration to structurally
      related pyrazolone compounds. Apart from its analgesic effect, the medication is
      an antipyretic and spasmolytic agent. The mechanism responsible for the analgesic
      effect is a complex one, and most probably rests on the inhibition of a central
      cyclooxygenase-3 and activation of the opioidergic system and cannabinoid system.
      Metamizole can block both PG-dependent and PG-independent pathways of fever
      induced by LPS, which suggests that this drug has a profile of antipyretic action
      distinctly different from that of NSAIDs. The mechanism responsible for the
      spasmolytic effect of metamizole is associated with the inhibited release of
      intracellular Ca2+ as a result of the reduced synthesis of inositol phosphate.
      Metamizole is predominantly applied in the therapy of pain of different etiology,
      of spastic conditions, especially affecting the digestive tract, and of fever
      refractory to other treatments. Co-administration of morphine and metamizole
      produces superadditive, antinociceptive effects. Metamizole is a relatively safe
      pharmaceutical preparation although it is not completely free from undesirable
      effects. Among these side-effects, the most serious one that raises most
      controversy is the myelotoxic effect. It seems that in the past the risk of
      metamizole-induced agranulocytosis was exaggerated. Despite the evidence showing
      no risk of teratogenic and embryotoxic effects, the drug must not be administered
      to pregnant women, although it is allowed to be given to pregnant and lactating
      animals. This paper seeks to describe the characteristics of metamizole in the
      light of current knowledge.

PMID- 24724494
TI  - A special issue on polymer conjugate based nanotherapeutics.

PMID- 24724495
TI  - Hyaluronic acid-based drug conjugates: state-of-the-art and perspectives.
AB  - Hyaluronan (HA) is biodegradable, highly biocompatible, and contains
      derivatizable functional groups along its backbone. This relatively simple, non
      branched polysaccharide can target specific cell surface receptors making it an
      attractive polymeric carrier for targeted delivery of therapeutic agents. This
      article provides an overview of recent developments involving small molecule and
      bio-macromolecule conjugates of HA as new generation of human therapeutic agents.
      Several approaches have been developed to prepare conjugates of HA with small
      molecule drugs, therapeutic peptides, antibodies, and nucleotides. This article
      discusses such approaches that can modulate the pharmacokinetic and
      biodistribution of these therapeutic agents so as to appreciate the design
      criteria for HA based (bio)conjugates or nanoparticles based on their in vitro
      assay and in vivo pharmacokinetic study.

PMID- 24724496
TI  - Hyaluronic acid-based conjugates for tumor-targeted drug delivery and imaging.
AB  - In recent years, hyaluronic acid (HA) has attracted significant interest in
      development of drug delivery systems because of its intrinsic physicochemical and
      biological properties, including water solubility, viscoeleasticity, non
      immunogenicity, biocompatibility, and biodegradability. In addition, HA has the
      ability to selectively bind specific receptors on the disease-related cells such
      as cancer cells and activated macrophages, followed by receptor-mediated
      endocytosis. Owing to these unique features, HA has been extensively used for
      development of the targetable carriers to deliver the therapeutic and imaging
      agents. In this review, we discuss the recent progress in various HA-based
      conjugates for cancer therapy and imaging, in which the active agents are
      covalently conjugated or physically encapsulated.

PMID- 24724497
TI  - Combining unique properties of dendrimers and magnetic nanoparticles towards
      cancer theranostics.
AB  - Magnetic nanoparticles (MNPs) are a well explored class of nanomaterials, known
      for their high magnetization and biocompatibility thus finding their way in
      several biomedical applications viz., drug delivery, magnetic resonance imaging
      contrast agent, immunoassay, detoxification of biological fluids and cell
      separation, biosensing and hyperthermia. On other hand, dendrimers are a class of
      hyperbranched, mostly symmetrical polymers that originate from a central core
      with repetitive branching units, called monomers, thus forming a globular
      structure. Due to their structural properties and controlled size, dendrimers
      have emerged as an attractive material for biomedical applications particularly
      as carriers for therapeutic cargo. Of late, researchers have started attempting
      to combine the unique features of dendrimer chemistry with the versatile magnetic
      nanoparticles to provide a facile platform for enhanced therapeutics and
      biomedical applications. This review intends to present the advances made towards
      fabrication of dendrimer based magnetic nanoparticles with varied surface
      architecture and their contribution towards theranostics, particularly for
      cancer.

PMID- 24724498
TI  - Interfering cancer with polymeric siRNA nanomedicines.
AB  - The ability to specifically silence genes using RNA interference (RNAi) has wide
      therapeutic applications for the treatment of disease. Numerous studies have
      demonstrated global gene and protein signatures distinguishing malignant and
      nonmalignant tissues. This worldwide pursuit of optimal cancer targets has so far
      provided a wide list of potential targets for each cancer type and for each
      patient, for which RNAi-based therapies can be applied. Nevertheless, due to poor
      stability of RNAi molecules in physiological conditions and their inability to
      cross cellular membranes, the delivery of siRNA and microRNA (miRNA) in vivo
      holds a great challenge and remains a crucial issue for their therapeutic
      success. Supramolecular carriers are often used in order to improve the
      physicochemical and biopharmaceutical properties of RNAi. Nano-sized delivery
      systems enable the accumulation of drugs and oligonucleotides (ONTs) in
      angiogenesis-dependent areas due to the enhanced permeability and retention (EPR)
      effect, and are able to cross cellular membranes and release the siRNA/miRNA only
      inside the target cell. In addition, a targeting moiety can increase the
      selectivity and specific uptake in the target tissue. Several vehicles
      (dendrimers, nanoparticles, liposomes, polyplex, lipoplex, polymeric
      nanoconjugates) are being developed for siRNA/miRNA delivery. These vehicles
      provide an important tool for exploiting the full potential of ONTs as
      therapeutic agents. In this review we will focus on the polymer-based approaches
      to deliver siRNA to cancer in vivo.

PMID- 24724499
TI  - Regulation of endocytosis by non-viral vectors for efficient gene activity.
AB  - Non-viral carriers, able to regulate cellular uptake pathways are becoming
      promising vectors for efficient gene transfer into cells because the
      intracellular processing of gene is strongly determined by the internalization
      pathways and subsequent intracellular routes. The intracellular processing of
      gene can be directed either to digestive or non-digestive way depending on the
      endocytosis mechanism. Enormous attempts have been made to bypass or avoid the
      digestive way of lysosomal degradation for meaningful delivery of therapeutic
      genes at the target site. This review describes an updated information regarding
      regulation of endocytosis pathways in consequence with the cellular trafficking
      and the determinant factors of the initial mode of internalization route for
      rational design of non-viral gene carriers. Firstly, we describe various nonviral
      gene vectors and the key barriers to non-viral gene transfer. Secondly, various
      major endocytosis pathways and their significance in developing non-viral gene
      carriers are discussed. Thirdly, various factors that potentially regulate
      endocytosis pathways of gene carriers to improve gene delivery efficacy are
      elaborately described. Lastly, the perspectives of future studies to control
      endocytosis mechanisms are discussed to design potential non-viral gene vectors
      for active application in future.

PMID- 24724500
TI  - Interaction of N-(2-hydroxypropyl)methacrylamide based homo, random and block
      copolymers with primary immune cells.
AB  - Polymer nanoparticles (NP), e.g., polymeric micelles, represent a promising
      platform for drug delivery including the field of immune modulation. In respect
      to this potential application, identification of chemical and structural
      properties that affect interaction of polymers with immune cells is an important
      step in their preclinical characterization. A series of well-defined,
      fluorescently labeled homopolymers, random as well as block copolymers based on
      the clinically approved N-(2-hydroxypropyl)methacrylamide (HPMA) were prepared to
      study the influence of polymer architecture on the interaction of polymers with
      primary human und murine immune cells systematically. The number average of the
      molar mass (M(n)) for all polymers was set to the range of 4-14 kDa with a
      varying ratio of hydrophilic and hydrophobic units and dispersities (D) in the
      range of 1.17-1.29. Cell uptake greatly depended on the polymer molecular weight
      and micro structure: Comparison of polymers of the same molar mass but varying
      ratio of hydrophilic and hydrophobic units revealed a strict dependency of
      cellular uptake on the size of the hydrophobic block. HPMA-ran-LMA copolymers
      with high amounts of lauryl side chains (15 and 20% LMA content) had highest
      internalization rates into human and mouse immune cells (monocytes, granulocytes,
      B and T cells). Our findings underline the role of particle size and composition
      of polymeric carriers in the field of nanomedicine.

PMID- 24724501
TI  - Receptor mediated cellular uptake of low molecular weight dendritic
      polyglycerols.
AB  - The development of effective polymer-based nanocarriers which are able to target
      diseased tissues still remains a great challenge in current research. Dendritic
      polyglycerols have emerged as novel polymeric scaffolds that have demonstrated a
      great potential for diverse biomedical applications. These architectures have
      already proven their usefulness in therapeutic approaches related to
      multivalency, given by the synergy between the nanosized dimensions combined with
      the high density of functional groups. However, a continuous effort is necessary
      to modify and tailor polyglycerol architectures to fit the future demands of
      biomedical applications. The present work deals with the development of a general
      synthetic strategy that allows the linkage of low molecular weight dendritic
      polyglycerols to fluorescent dyes and cell targeting ligands. The receptor
      mediated cellular uptake of the polyglycerol conjugates highlight their potential
      to acts as new targeted nanocarriers that should be able to decrease non-specific
      cellular uptake.

PMID- 24724502
TI  - The modulation of the permeability and the cellular uptake of liposome by stable
      anchoring of lipid-conjugated pluronic on liposome.
AB  - Controlling the permeability of liposome is important to modulate the release
      behavior of drug from the liposome. Pluronic F127 (PF127) is a biocompatible tri
      block copolymer, which can interact with lipid bilayer of liposomes and make
      leakages that allow the release of hydrophilic substance from liposome interior.
      However, the interaction between unmodified PF127 and lipid bilayer is not very
      strong and the incorporated PF127 is easily desorbed from the liposomes in an
      infinite reservoir condition. In this paper, we conjugated lipid molecule (1,2
      distearoyl-sn-glycero-3-phosphoethanolamine [DSPE]) at the both ends of PF127 to
      increase the interaction between polymer and liposome. This lipid-conjugated
      PF127 was incorporated into the liposomes and it remained stably without
      desorption from liposomes in an infinite reservoir condition. The stably bound
      PF127 increased the release rate of hydrophilic drug from liposomes in a dose
      dependent manner. Moreover, the lipid-conjugated PF127 changed the surface
      property of liposomes and inhibited its cellular uptake when the incorporated
      amount was above 2.5 wt%. In conclusion, the lipid-conjugated PF127 could
      function as a stable anchor on the lipid bilayer of liposomes to control the
      permeability as well as provide the hydrophilic surface of liposomes in an open
      system like an in vivo situation.

PMID- 24724503
TI  - Biocompatible amphiphilic pentablock copolymeric nanoparticles for anti-cancer
      drug delivery.
AB  - A pentablock copolymer of Poly(Lactide-co-Glycolide) and Pluronic F68 was
      synthesized using ring-opening polymerization and characterized by NMR and FTIR
      for confirming the structure of the block copolymer. TG-DTA studies showed
      PLGA:Pluronic ratio to be 4:1. As the PLGA-PEO-PPO-PEO-PLGA Pentablock Copolymer
      (PPPC) prepared is amphiphilic, its Critical Vesicular Concentration, was
      measured, which was lower at 37 degrees C than at 25 degrees C, which could
      provide better stability to the system at physiological temperature. The
      nanoparticles of PPPC vary in topographyand range from 150 to 500 nm in size,
      according to the synthesis route used viz Emulsion Solvent Evaporation and simple
      dialysis. Pentablock copolymer nanoparticles were found to entrap about 84% of
      hydrophobic drug, docetaxel. Drug release profile of docetaxel showed about 50%
      release in first 2 hours at pH 4.6 and about 80% docetaxel was released at pH
      7.4, at the end of 2 days. The PPPC nanoparticles was found to be biocompatible
      to L929 cell lines up to 1 mg/ml concentration. Preliminary in vitro cytotoxic
      effect of docetaxel loaded PPPC nanoparticles against four different cancer cell
      lines showed 50% inhibitory concentration of 6 nM in A431 (Squamous cell
      carcinoma), 250 nM in HeLa (Cervical carcinoma), 800 nM in PC3 (Prostate
      carcinoma) and 1 microM in KB (Epidermoid carcinoma) cells.

PMID- 24724504
TI  - Polymer functionalized single walled carbon nanotubes mediated drug delivery of
      gliotoxin in cancer cells.
AB  - During recent years, significant development has been achieved in carbon nanotube
      conjugated with polymer system for drug delivery system (DDS). In the present
      study, we have prepared functionalized single walled carbon nanotube conjugated
      with chitooligosaccharide (f-SWNT-COS) as a Drug Delivery System. In addition,
      drug Gliotoxin (GTX) and targeting molecules (Lysozyme, p53 and Folic acid) have
      been incorporated into f-SWNT-COS. f-SWNTs-COS-GTX-p53, f-SWNTs-COS-GTX-lysozyme,
      f-SWNTs-COS-GTX-FA have been physiochemically characterized for DDS. FT-IR, SEM
      and TEM analysis confirmed the formation of chemical interaction and polymer
      coating. FT-IR result clearly confirmed the interaction between f-SWNT and COS.
      The effective drug release was monitored against cervical cancer (HeLa) cells and
      Breast Cancer (MCF-7) cells and it was found that all the three drug delivery
      systems showed significant cytotoxicity. f-SWNTs-COS-GTX-p53 delivery vehicle and
      its effective cytotoxicity on HeLa cells was further checked with fluorescent
      activated cell sorter analysis. Our results suggest that the f-SWNTs-COS-GTX-p53
      is the most effective delivery vehicle with a controlled release and enhanced
      cytotoxicity rendered through apoptosis in human cervical cancer (HeLa) cells.
      These systems can further be used for the delivery of other commercially
      available anti cancer drugs as well.

PMID- 24724505
TI  - Heparin-anthranoid conjugates associated with nanomagnetite particles and their
      cytotoxic effect on cancer cells.
AB  - The paper describes a methodology for preparing monodisperse, water-soluble
      magnetite nanoparticles, coated with heparin and loaded with 4,5-dihydroxy-9,10
      dioxoanthracene-2-carboxylic acid (Rhein), able to be used as a drug delivery
      system for cancer chemotherapy. Upon preparation, nanoparticles structure and
      morphology were investigated. The surface charge and the equivalent dimensions of
      the nanoparticles dispersed in water were measured, as a function of the
      suspension pH. The concentration of the drug into the nanoparticles shell, and
      the drug release profile was determined. The functionality of Rhein-loaded
      heparin-coated magnetic nanoparticles was assessed by monitoring their cytotoxic
      effect on cultured human tumor hepatocyte cell line, HepG2, using MTT assay. We
      found that upon exposure of HepG2 cells to Rhein-loaded heparin-coated
      nanoparticles, the cell viability was drastically reduced (to approximately 10%)
      as compared to that of the cells exposed to the free drug, indicating the
      potential of these magnetite nanoparticles to be used in cancer therapy.

PMID- 24724506
TI  - Polyaspartic acid functionalized gold nanoparticles for tumor targeted
      doxorubicin delivery.
AB  - In this paper, we present polyaspartic acid, a biodegradable polymer as a
      reducing and functionalizing agent for the synthesis of doxorubicin loaded gold
      nanoparticles by a green process. Gold nanoparticles were stable to electrolytes
      and pH. Secondary amino groups of polyaspartic acid enabled reduction of gold
      chloride to form gold nanoparticles of size 55 +/-10 nm, with face centered cubic
      crystalline structure as confirmed by UV, TEM, SAED and XRD studies. Cationic
      doxorubicin was readily loaded onto anionic polyaspartic acid gold nanoparticles
      by ionic complexation. Fluorescence studies confirmed doxorubicin loading while
      FTIR spectra confirmed ionic complexation. Doxorubicin loading onto polyaspartic
      acid gold nanoparticles was studied at doxorubicin/polyaspartic acid molar ratios
      1:10 to 1:1. As the molar ratio tended to unity, although loading up to 60% was
      achieved, colloidal instability resulted and is attributed to effective covering
      of negative charges of polyaspartic acid. Stable doxorubicin loaded polyaspartic
      acid gold nanoparticles of 105 +/- 15.1 nm with doxorubicin loading of 23.85% w/w
      and zeta potential value of -28 +/- 0.77 mV were obtained at
      doxorubicin/polyaspartic acid molar ratio 1:10. Higher doxorubicin release rate
      from the doxorubicin loaded polyaspartic acid gold nanoparticles in an acid
      medium (i.e., pH 5.5) as compared to that in pH 7.4 and deionized water is a
      desirable characteristic for tumor targeted delivery. Enhanced cytotoxicity and 3
      fold higher uptake of doxorubicin loaded polyaspartic acid gold nanoparticles as
      compared to doxorubicin solution were seen in MCF-7 breast cancer cells while
      polyaspartic acid gold nanoparticles revealed no cytotoxicity confirming safety.
      Prominent regression in tumor size in-vivo in fibrosarcoma tumor induced mouse
      model was observed upto 59 days with doxorubicin loaded polyaspartic acid gold
      nanoparticles while doxorubicin solution treated mice showed regrowth beyond 23rd
      day. Moreover, a decrease of body weight of 35% indicating severe toxicity with
      doxorubicin solution as compared to only 20% with gradual recovery after day 30
      in case of doxorubicin loaded polyaspartic acid gold nanoparticles confirmed
      their lower toxicity and enhanced efficacy.

PMID- 24724507
TI  - Biodistribution and pharmacokinetics in rats and antitumor effect in various
      types of tumor-bearing mice of novel self-assembled gelatin-oleic acid
      nanoparticles containing paclitaxel.
AB  - The aim of this study was to investigate the pharmacokinetics and biodistribution
      in Sprague-Dawley rats, anti-tumor activity and acute toxicity in different tumor
      bearing mice of novel biocompatible nanoparticles. Paclitaxel (PTX) was selected
      as a model drug and loaded on different tumor types and at various doses. The
      nanoparticles were prepared using a newly synthesized gelatin-oleic acid
      conjugate via self-assembly in an aqueous solution. The nanoparticles were
      further functionalized using folic acid (FA) as a targeting ligand for cancer.
      The in vivo effects of the nanoparticles were compared with the commercially
      available Taxol (a solution form of PTX) as a reference dosage form. The in vivo
      studies confirmed that nanoparticles showed improved therapeutic effects on
      tumors and significantly reduced the toxic effects associated with Taxol, even at
      the 50% lethal dose (LD50). The in vivo pharmacokinetic parameters and
      biodistribution of the nanoparticles containing PTX also indicated slower
      clearance, longer blood circulation and higher tumor selectivity. Furthermore,
      the functionalized nanoparticles with FA were more effective than the non
      functionalized nanoparticles. Thus, the suitable properties of gelatin-oleic
      nanoparticles (GON) as a drug carrier and the effective targeting ligand could
      synergistically maximize the in vivo anti-tumor efficacy resulting in delayed
      tumor volume growth and hence, providing versatile strategies in cancer therapy
      and drug delivery.

PMID- 24724508
TI  - PTH 1-34 loaded thiolated chitosan nanoparticles for osteoporosis: oral
      bioavailability and anabolic effect on primary osteoblast cells.
AB  - In this work, biocompatible and mucoadhesive thiolated chitosan (TCS) was used in
      the preparation of oral nanoformulation of human parathyroid hormone 1-34 (PTH 1
      34) as an alternative patient compliant route in treating osteoporosis. PTH 1-34
      loaded thiolated chitosan nanoparticles (TCS-PTH 1-34 NPs) size, morphology and
      interaction was analysed by DLS, SEM and FTIR respectively. TCS-PTH 1-34 NPs (90
      100 nm) with 60% encapsulation efficiency was subjected to an in vitro release in
      simulated rat body fluids. TCS-PTH 1-34 NP's treated human primary osteoblast
      cells (HOB) upon PTH 1-34 receptor activation, produced second messenger-cAMP
      which down stream stimulated, production of bone specific alkaline phosphatase,
      osteocalcin and even enhanced the intracellular calcium uptake. These data
      substantiates the anabolic effect and bioactivity of the PTH 1-34 released from
      the TCS-PTH 1-34 NPs. Bare PTH 1-34 failed to reach the systemic circulation
      following oral dosage in rats whereas TCS-PTH 1-34 NPs showed an oral
      bioavailability of 0.075 microg PTH 1-34 throughout 48 h which is indeed a
      significant improvement in the half life of this peptide. TSC-PTH 1-34 NPs have
      released an advantageous anabolic dose of the peptide in blood that is suited for
      the treatment of osteoporosis. NIR image of gastrointestinal transit of ICG
      conjugated nanoformulation supports and justifies this significant finding. These
      results cumulatively point out that TCS NPs loaded with PTH 1-34 is efficient in
      orally delivering the peptide. This route of administration has increased its
      half life and improved the bioavailability compared to the bare peptide that is
      delivered systemically for treating osteoporosis.

PMID- 24724509
TI  - Drive theory and home run milestones in baseball: an historical analysis.
AB  - The purpose of this investigation was to test whether the performance of the home
      run hitters in Major League Baseball adhered to predictions of Drive Theory. 24
      baseball players who have hit at least 505 home runs were included in the sample.
      Their performance was assessed around the time in which they reached a
      significant home run career milestone, operationalized as either 500 or 600 home
      runs, or surpassing the league's home run record. As predicted, the players were
      found to require significantly more at-bats to complete the 5 home runs before
      the milestone, when stress was assumed to be mounting, than the 5 home runs after
      the milestone. In contrast, those players who reached the personal landmark from
      1988 (the suspected commencement of the so-called "Steroid Era") onwards required
      the same number of at-bats before and after the milestone.

PMID- 24724510
TI  - Inventories of psychological skills for athletic clubs and school life.
AB  - Some students who participate in athletic activities transfer the skills acquired
      in a sports context into other areas of life, while others do not. To identify
      the specific skills that are transferred or not from sports to the school
      environment, two inventories were developed: the "Psychological Skills Inventory
      for Athletic Clubs" and the "Psychological Skills Inventory for School Life."
      These inventories enable a comparison of skills in a sport context with skills in
      a school context. In the first stage, 307 Japanese first-year university students
      who had participated in high school athletic clubs volunteered to take part in a
      survey to develop these inventories. Analyses indicated that both inventories
      comprised identical subscales of intrapersonal and interpersonal skills. In the
      second stage, the reliability and validity of these inventories was confirmed for
      531 Japanese high school students who were members of athletic clubs for sports
      such as soccer and baseball.

PMID- 24724511
TI  - Validity and reliability of Greek versions of two scales assessing family and
      friend support for exercise behaviour.
AB  - This study examined the validity and reliability of Greek versions of two scales
      assessing family and friend support for exercise behaviour. Exploratory factor
      analyses (EFAs) and confirmatory factor analyses (CFAs) were performed in a
      sample of 360 students. Additionally, CFAs were applied in a second sample of 726
      physically active adults. Finally, associations were examined among scales and
      physical activity, exercise self-efficacy, and socio-demographic variables.
      Results indicated (a) a two-factor model for the Family Support for Exercise
      Behaviour Scale, (b) a one-factor solution for the Friend Support for Exercise
      Behaviour Scale, (c) satisfactory reliability coefficients, and (d) associations
      among the scales and physical activity, self-efficacy and socio-demographic
      variables. Conclusively, the social support scales were valid and reliable.

PMID- 24724512
TI  - Mediating factors in martial arts and combat sports: an analysis of the type of
      martial art, characteristics, and social background of young participants.
AB  - To date, most studies regarding the social-psychological effects of martial arts
      and combat sports (MA&CS) on young people focus on measuring effects without
      considering mediating factors. The aim of the present study was to analyze three
      mediating factors that might be influential when examining outcomes of MA&CS for
      youth (i.e., the type of MA&CS, participants' characteristics, and social
      background). Young MA&CS participants (N = 477, M age = 14.0 yr., SD = 2.13)
      practicing judo, aikido, kick-/Thai boxing or karate, as well as their parents (N
      = 307), were assessed in terms of their goal orientations, aggressiveness,
      psychosocial behavior, and social background. It was concluded that differences
      exist in the characteristics and social background of participants depending on
      the type of MA&CS being practiced. The fact that differences in these mediating
      factors can be identified indicates that in future research these and possible
      other mediating factors should be considered when trying to determine social
      psychological outcomes of MA&CS.

PMID- 24724513
TI  - Influence of acute high-intensity aerobic interval exercise bout on selective
      attention and short-term memory tasks.
AB  - Acute moderate intensity continuous aerobic exercise can improve specific
      cognitive functions, such as short-term memory and selective attention. Moreover,
      high-intensity interval training (HIT) has been recently proposed as a time
      efficient alternative to traditional cardiorespiratory exercise. However,
      considering previous speculations that the exercise intensity affects cognition
      in a U-shaped fashion, it was hypothesized that a HIT session may impair
      cognitive performance. Therefore, this study assessed the effects of an acute HIT
      session on selective attention and short-term memory tasks. 22 healthy middle
      aged individuals (M age = 53.7 yr.) engaged in both (1) a HIT session, 10 1 min.
      cycling bouts at the intensity corresponding to 80% of the reserve heart rate
      interspersed by 1 min. active pauses cycling at 60% of the reserve heart rate and
      (2) a control session, consisting of an active condition with low-intensity
      active stretching exercise. Before and after each experimental session, cognitive
      performance was assessed by the Victoria Version of the Stroop test (a selective
      attention test) and the Digit Span test (a short-term memory test). Following the
      HIT session, the time to complete the Stroop "Color word" test was significantly
      lower when compared with that of the control session. The performances in the
      other subtasks of the Stroop test as well as in the Digit Span test were not
      significantly different. A HIT session can improve cognitive function.

PMID- 24724514
TI  - From specific training to global shift of manual preference in Kung Fu experts.
AB  - Manual preference and intermanual performance asymmetry have been approached from
      a multidimensional and dynamic perspective. A point of interest from that
      approach is the role of lateralized motor experiences on handedness. In this
      study, intermanual performance asymmetry in sport-specific movements and manual
      preference in daily living tasks were compared between Kung Fu athletes and
      novices. Analysis of movement time in the performance of interlaterally symmetric
      and asymmetric movement patterns showed smaller intermanual performance asymmetry
      in experts. Analysis of manual preference using the Edinburgh Handedness
      Inventory indicated that experts presented predominantly weak or moderate
      strength of right hand preference. Novices, conversely, were found to have
      predominantly strong right hand preference. These results suggest that extensive
      bimanual training by experts leads to a global shift of manual preference,
      affecting hand selection in distinct tasks.

PMID- 24724515
TI  - Temporal coupling of eye gaze and cursor on key buttons during text-entry tasks.
AB  - Coupling patterns of eye gaze and cursor movements on key buttons were
      investigated during a practical text-entry task. A text-entry task can be
      described as a series of goal-directed aiming tasks. In a typical goal-directed
      aiming task, eye movements generally lead cursor movements; eye gaze arrives at
      the target and starts moving to the next target before the cursor. However, in
      10% of cases in this experiment, the cursor arrived at the target earlier than
      the eye gaze did, regardless of text entry speed. Eye gaze started toward the
      next target key button after the start of the cursor's movement in 57% of cases,
      which also varied with text-entry speed. The coupling patterns, which differed
      from those observed in typical goal-directed aiming tasks, might be due to the
      speed requirement of practical text-entry tasks, memory of key button positions,
      and the use of peripheral vision.

PMID- 24724516
TI  - Warm-up with weighted bat and adjustment of upper limb muscle activity in bat
      swinging under movement correction conditions.
AB  - The effects of weighted bat warm-up on adjustment of upper limb muscle activity
      were investigated during baseball bat swinging under dynamic conditions that
      require a spatial and temporal adjustment of the swinging to hit a moving target.
      Seven male college baseball players participated in this study. Using a batting
      simulator, the task was to swing the standard bat coincident with the arrival
      timing and position of a moving target after three warm-up swings using a
      standard or weighted bat. There was no significant effect of weighted bat warm-up
      on muscle activity before impact associated with temporal or spatial movement
      corrections. However, lower inhibition of the extensor carpi ulnaris muscle
      activity was observed in a velocity-changed condition in the weighted bat warm
      up, as compared to a standard bat warm-up. It is suggested that weighted bat warm
      up decreases the adjustment ability associated with inhibition of muscle
      activation under movement correction conditions.

PMID- 24724517
TI  - Relative sensitivity of depth discrimination for ankle inversion and plantar
      flexion movements.
AB  - 25 participants (20 women, 5 men) were tested for sensitivity in discrimination
      between sets of six movements centered on 8 degrees, 11 degrees, and 14 degrees,
      and separated by 0.3 degrees. Both inversion and plantar flexion movements were
      tested. Discrimination of the extent of inversion movement was observed to
      decline linearly with increasing depth; however, for plantar flexion, the
      discrimination function for movement extent was found to be non-linear. The
      relatively better discrimination of plantar flexion movements than inversion
      movements at around 11 degrees from horizontal is interpreted as an effect
      arising from differential amounts of practice through use, because this position
      is associated with the plantar flexion movement made in normal walking. The fact
      that plantar flexion movements are discriminated better than inversion at one
      region but not others argues against accounts of superior proprioceptive
      sensitivity for plantar flexion compared to inversion that are based on general
      properties of plantar flexion such as the number of muscle fibres on stretch.

PMID- 24724518
TI  - Influence of prior use of the same or different effectors in a reaching action.
AB  - Use of different effectors in two consecutive actions could generate an
      attentional shift between the effectors with shorter latencies in the second
      action of reaching. 18 participants (10 men; M age = 21.3 yr.) participated in an
      experiment with two main variables: (1) effector switching with two levels
      (Switching and No Switching), where the participants use or do not use a
      different motor effector for each action; (2) lifting muscles, i.e., the muscles
      involved in the first phase of the reaching, with two levels (finger-lifting
      muscle and palm-lifting muscle). Premotor time, Motor time, Reaction time,
      Movement time, and Total time were measured. For Premotor, Movement, and Total
      times, faster responses were observed when there was no switching of the
      effector. This delay could be due to an attentional shift between motor effectors
      and its relations with motor processes. Possible applications include the
      ergonomic design of device controls, considering that the use of the same
      effector is beneficial when fast reaction times are sought.

PMID- 24724519
TI  - Personality traits and exercise capacity in male athletes and non-athletes.
AB  - To investigate the relationships between personality traits and athletic
      capacity, this study compared a sample of 376 young adult men (169 athletes, 207
      non-athletes; M age = 23.8 yr., SD = 3.9). 26 lab-based exercise capacity
      parameters were measured, as well as the Big Five major personality traits using
      the NEO Five-Factor Inventory. The results indicated that athletes scored higher
      than non-athletes for Conscientiousness but scores were not statistically
      different between groups for other personality traits. Team sport athletes scored
      higher on Extraversion than endurance athletes. All the personality traits were
      associated with some of the exercise capacity indices; however, these
      correlations were rather weak (rs < .2).

PMID- 24724520
TI  - Effect of osteoarthritis on accuracy of continuous tracking leg movement.
AB  - The purpose of this study was to establish if osteoarthritis in older adults was
      associated with ability to accurately and continuously track leg movement in a
      model of therapy to improve age-related impairments of proprioception,
      kinesthesia, and coordination of muscles at the knee joint. 24 older adults
      without osteoarthritis and 24 older adults with osteoarthritis participated.
      Software generated a moving, on-screen sine wave and a vertically traveling disc.
      Participants attempted to keep the disc on the sine wave by bending and
      straightening the leg. Older adults without osteoarthritis performed better than
      older adults with osteoarthritis in one of two conditions. There was a
      relationship between osteoarthritis and reduced accuracy of leg movement. Further
      research will be required to specifically define this relationship and to
      establish if such interventions to improve accuracy of knee movement will
      positively affect functional capabilities of individuals with osteoarthritis.

PMID- 24724521
TI  - Again, knowledge of common source fails to promote visual-haptic integration.
AB  - The present study tested whether knowledge of a common source of conflicting
      visual-haptic stimulation promotes intersensory integration. 40 undergraduates
      manually felt the size of a square while viewing it through a lens that minified
      its visual size by half. Participants, however, could experience the haptic and
      the visual stimulation as emanating from either a common source or different
      sources. Their subsequent matches of the perceived size were biased by the felt
      size of the square, irrespective of whether they experienced the intersensory
      stimulation as coming from one or two sources. These results strengthen previous
      findings suggesting that the integration of sensory discordant information
      depends on bottom-up rather than on top-down processes.

PMID- 24724522
TI  - Effects of anticipation on perception of facial expressions.
AB  - Human beings do not passively perceive the facial expressions of other people,
      but predict observed facial expressions by employing past experiences. The aim of
      the current study was to investigate whether and how anticipation affected the
      perception of facial expressions. A 3-way repeated-measures ANOVA on
      anticipation, orientation, and facial expression was performed on RTs and
      recognition accuracy in Experiments 1 and 2. The results showed that anticipation
      reduced susceptibility to negative facial expressions. In this regard,
      anticipation might be considered as an effective emotion-regulation strategy. In
      addition, a decreased inversion effect for positive facial expressions was found
      in the predictable condition, which might reflect a switch from feature-based to
      holistic processing.

PMID- 24724523
TI  - Effects of sentence context on phonemic categorization of natural and synthetic
      consonant-vowel tokens.
AB  - The purpose was to assess if phonemic categorization in sentential context is
      best explained by autonomous feedforward processing or by top-down feedback
      processing that affects phonemic representation. 11 listeners with normal
      hearing, ages 20-50 years, were asked to label consonants in /pi/-/ti/ consonant
      vowel (CV) stimuli in 9-step continua. One continuum was derived from natural
      tokens and the other was synthetically generated. The CV stimuli were presented
      in isolation and in three sentential contexts: a neutral context, a context
      favoring /p/, and a context favoring /t/. For both natural and synthetic stimuli,
      the isolated and neutral context sentences yielded significantly more /t/
      responses than sentence contexts primed for either /p/ or /t/. No other
      conditions were significantly different. Results did not show easily explainable
      semantic context effects. Instead, data clustering was more readily explained by
      top-down feedback processing affecting phonemic representation.

PMID- 24724524
TI  - Psychoanalysis, artistic obsession, and artistic motivation: the study of
      pathography.
AB  - A modern assessment of Freud's conceptualization of the creative process focusing
      on drives, ego psychology, and object relation theory is presented. 40 artists
      and musicians were interviewed employing 13 open-ended questions to provoke
      responses historically associated with the theoretical conceptualizations of
      Freud and post-Freudian theory related to the creative process. Creative process
      was defined as internal object relations that motivate the external connection
      between artist and the creative work. Measured responses concerning purpose and
      understanding; motivation before, during, and after performance; obstacles in
      performance; and needs through the creative process were assessed. Cluster
      analysis segregated the participants into high, medium, and low agreement groups
      based on similarity of responses. A multivariate stepwise regression revealed
      four questions (enlightenment, drives, obstacles, and ought self discrepancies)
      accounted for 83.9% of the variance. A post hoc discriminant function analysis
      identified 82.5% of the population to their correct groups. The findings support
      Spitz's (2005) suggestion that we regard "drives, ego psychology, and object
      relation theory not as separate approaches but as parts of a whole with varying
      stresses or accents" (p. 503).

PMID- 24724525
TI  - Health-related physical activity levels in Spanish youth and young adults.
AB  - The aim of this study was to analyze the current physical activity (PA) levels in
      youth and young adults from Granada, Spain, and to assess if they accomplish the
      recommendations for healthy PA. A sample of 1,832 boys and 1,840 girls was
      administered the International Physical Activity Questionnaire. Results showed
      that most of the children (72.2%) and adolescents (56.4%) reached the recommended
      PA levels, whereas only 40% of young adults achieved recommended levels of PA.
      The most active were students from Primary schools, whereas university students
      were the least active. Youth of college and university ages were found to be at
      higher risk for engagement in PA.

PMID- 24724526
TI  - Repetition duration influences ratings of perceived exertion.
AB  - This study investigated the effect of different repetition durations on ratings
      of perceived exertion (RPE) in active muscles (RPE-AM) and the overall body (RPE
      O). 19 male volunteers (M age = 25.4 yr., SD = 3.5) performed strength training
      protocols with multiple sets matched by the number of sets and repetitions,
      intensity and rest interval but different repetition durations: 4 sec., 6 sec.,
      or self-paced. Participants were asked to estimate their RPE-AM and RPE-O after
      each set. Training protocols with a 6-sec. repetition duration produced distinct
      responses on RPE during and after performance compared to 4-sec. and self-paced
      durations. However, there were no significant differences between 4-sec. and self
      paced durations.

PMID- 24724527
TI  - Factors associated with self-reported arthritis 7 to 24 years after a traumatic
      brain injury.
AB  - The purpose of this study was to profile characteristics of people with traumatic
      brain injury (TBI) who self-reported arthritis 7 to 24 yr. post-injury. Pre- and
      post-injury socio-demographic factors, injury-related factors, and postinjury
      standardized assessments measuring health, activity, and participation outcomes
      were assessed in a retrospective cohort study of 274 participants. The group self
      reporting arthritis had significantly more sleep disturbances, poorer overall
      health, lower mental health and physical function, and decreased productivity.
      Also, they were older and reported a shorter length of loss of consciousness from
      TBI. These resulted suggest that musculoskeletal complaints from long-term
      survivors of TBI sholud be addressed in post-acute care and could guide future
      research on arthritis in the TBI population.

PMID- 24724528
TI  - Association of leg bias with bipedal speed and power in developing soccer
      players.
AB  - The aim of this research was to determine whether there is any association
      between leg bias and bipedal locomotion in young male soccer players. 227
      participants, members of a Polish football club, were tested. Leg dominancy and
      maximal specific power of each leg were recorded.

PMID- 24724529
TI  - Inclusive intervention to enhance the fundamental movement skills of children
      without hearing: a preliminary study.
AB  - The purpose of this study was to assess an intervention program on the
      fundamental movement skill of students with and without hearing impairment, using
      the Test of Gross Motor Development-2 (TGMD-2) standardized Turkish norm.
      Preschool children with and without hearing impairment participated in this
      study. At the beginning of the study, most of the children with hearing
      impairment demonstrated developmental delay on the Locomotor subscale (6/7), as
      did about one-third (4/11) of the children without hearing impairment. For the
      Object control subscale, 4/7 of children with hearing impairment and none without
      hearing impairment showed developmental delay prior to the intervention program.
      After the intervention program, 3/7 children with hearing impairment had
      developmental delay on the Locomotor subscale. On the Object control subscale,
      2/7 children with hearing impairment and none without hearing impairment showed
      developmental delay. The six-week intervention program improved TGMD-2 scores of
      children with hearing impairment, yet did not yield statistically significant
      improvement of fundamental movement skills.

PMID- 24724531
TI  - Vaporization of protic ionic liquids studied by matrix-isolation Fourier
      transform infrared spectroscopy.
AB  - Several protic ionic liquids (PILs) with a wide range of pK(a) differences
      (DeltapK(a)) between the parent acid and base molecules were thermally evaporated
      in vacuum, trapped on a CsI plate by a cryogenic neon matrix-isolation method,
      and studied by Fourier transform infrared spectroscopy and density functional
      theory calculations. The parent neutral molecules and proton-transferred cation
      anion pair species were identified as chemical components evaporated from the
      PILs with lower and higher DeltapK(a) values, respectively. The DeltapK(a)
      dependent vaporization mechanism is discussed in terms of thermodynamic
      equilibrium between acid-base and anion-cation systems in the liquid phase.

PMID- 24724532
TI  - Pacemaker diagnostics in atrial fibrillation: limited usefulness for therapy
      initiation in a pacemaker practice.
AB  - AIM: We aimed to determine the practical value of pacemaker diagnostics for
      atrial fibrillation (AF) in an unselected general pacemaker practice,
      specifically workflow and initiation of anticoagulation or antiarrhythmic drug
      (AAD) therapy. METHODS: We prospectively followed consecutive pacemaker
      interrogations over a period of 1 year to identify patients with AF (burden from
      1% to 99%). We contacted referring physicians with AF details, and then
      determined whether the information resulted in therapeutic changes. RESULTS: Of
      the 1,100 pacemakers interrogated, 728 were dual chamber (DDDs) with AF
      diagnostic capability. AF was recorded in 73 (10%) but seven had limited
      information, leaving 66 patients; of these, 42 (63%) patients were already
      anticoagulated and in five (7%) patients, anticoagulation had been stopped
      because of complications. Initial diagnosis of AF was made by the pacemaker in 17
      patients (26% of 66; 2% of 728); four (6% of 66) patients were newly initiated on
      anticoagulation. Of the 66 patients, 17 patients were already on AADs; 49 (74%)
      had satisfactory rate control or had other issues; only two (3% of 66; 0.3% of
      728) received new AADs. CONCLUSIONS: Of 728 patients with DDD pacemakers, only 17
      were newly discovered to have AF, and six (0.8%) had changes in medications based
      on the pacemaker data. Adding pacemaker-derived data to existing clinical
      information had little therapeutic impact, due to a combination of cumbersome
      workflow, and because AF was usually known to practitioners. Developments in
      automated monitoring systems may provide more accessible and therapeutically
      useful information.

PMID- 24724533
TI  - Impact of graft nephrectomy on outcomes of second kidney transplantation.
AB  - OBJECTIVES: To determine the impact of renal graft nephrectomy on second kidney
      transplantation survival. METHODS: We carried out a retrospective single-center
      study by analyzing cases performed from January 2000 to December 2011.
      Retransplanted patients who underwent previous allograft nephrectomy more than 3
      months post-transplantation (group 1) were compared with those who did not (group
      2) in terms of graft survival, incidences of acute rejection and delayed graft
      function. Multivariate Cox proportional hazard models were used to assess risk
      factors of graft loss after retransplantation. RESULTS: Overall, 146 patients
      were analyzed, including 52 (35.6%) in group 1 and 94 (64.4%) in group 2. Group 1
      patients presented a significantly shorter first graft survival (0.8 vs 8.6
      years, P < 0.001) and more anti-class I antibodies (90.5% vs 74.2%, P = 0.03). A
      total of 10 patients (19%) in group 1 and 16 patients (17%) in group 2 had at
      least one acute rejection episode (P = 0.74). Delayed graft function was observed
      in 13 patients (25%) in group 1 and 17 patients (18%) in group 2 (P = 0.32).
      Graft survival at 1, 5 and 10 years was, respectively, 94%, 81% and 58% in group
      1, and 99%, 93% and 66% in group 2 (P = 0.10). Graft survival was decreased by
      increased donor age and serum creatinine, and tended to be associated with post
      transplantation presence of anti-class I and II antibodies. Graft nephrectomy was
      not associated with graft survival in multivariate analysis. CONCLUSIONS: Graft
      nephrectomy, probably a marker of high immunological risk patients, is not a risk
      factor of increased retransplant failure.

PMID- 24724534
TI  - How placental growth factor detection might improve diagnosis and management of
      pre-eclampsia.
AB  - Pre-eclampsia complicates around 5% of pregnancies and hypertensive disorders of
      pregnancy are responsible for over 60,000 maternal deaths worldwide annually.
      Identifying women with pre-eclampsia is a major goal of antenatal care in order
      to target increased surveillance, allow stabilizing therapies to be implemented
      and to enable timely delivery. Current risk assessment is based on clinical
      history, imperfect assessment of clinical signs (e.g., hypertension and
      proteinuria) and nonspecific biochemical markers, all of which are subject to
      considerable error. This is further confounded by underlying maternal disease
      such as chronic hypertension or renal pathology. Angiogenic factors reflect the
      underlying pathophysiology of pre-eclampsia and there is emerging evidence that
      they can now be used for more accurate risk assessment. The most promising of
      these factors include placental growth factor and soluble fms-like tyrosine
      kinase-1. Used at point of care, these can accurately discriminate true disease
      in suspected cases and subsequent need for delivery.

PMID- 24724535
TI  - Synthesis of alpha,alpha'-trans-oxepanes through an organocatalytic oxa-conjugate
      addition reaction.
AB  - Oxepanes are found in a wide range of natural products; however, they are
      challenging synthetic targets due to enthalpic and entropic barriers.
      Organocatalytic oxa-conjugate addition reactions promoted by the gem
      disubstituent (Thorpe-Ingold) effect stereoselectively provided alpha,alpha'
      trans-oxepanes. In addition, the potential of an organocatalytic tandem oxa
      conjugate addition/alpha-oxidation was demonstrated in a rapid generation of
      molecular complexity. These organocatalytic oxa-conjugate addition reactions
      would provide powerful tools for the synthesis of natural products that contain
      highly functionalized oxepanes. 

PMID- 24724536
TI  - Thermodynamic properties of the effector domains of MARTX toxins suggest their
      unfolding for translocation across the host membrane.
AB  - MARTX (multifunctional autoprocessing repeats-in-toxin) family toxins are
      produced by Vibrio cholerae, Vibrio vulnificus, Aeromonas hydrophila and other
      Gram-negative bacteria. Effector domains of MARTX toxins cross the cytoplasmic
      membrane of a host cell through a putative pore formed by the toxin's glycine
      rich repeats. The structure of the pore is unknown and the translocation
      mechanism of the effector domains is poorly understood. We examined the
      thermodynamic stability of the effector domains of V. cholerae and A. hydrophila
      MARTX toxins to elucidate the mechanism of their translocation. We found that all
      but one domain in each toxin are thermodynamically unstable and several acquire a
      molten globule state near human physiological temperatures. Fusion of the most
      stable cysteine protease domain to the adjacent effector domain reduces its
      thermodynamic stability ~ 1.4-fold (from D G H 2 O 21.8 to 16.1 kJ mol(-1) ).
      Precipitation of several individual domains due to thermal denaturation is
      reduced upon their fusion into multi-domain constructs. We speculate that low
      thermostability of the MARTX effector domains correlates with that of many other
      membrane-penetrating toxins and implies their unfolding for cell entry. This
      study extends the list of thermolabile bacterial toxins, suggesting that this
      quality is essential and could be susceptible for selective targeting of
      pathogenic toxins.

PMID- 24724537
TI  - Is pulmonary cryptococcosis a unique pathology?

PMID- 24724538
TI  - Intraoperative evaluation of right ventricular outflow tract myxoma by real time
      three-dimensional transesophageal echocardiography.
AB  - Cardiac myxoma arising form right ventricular outflow tract (RVOT) is extremely
      rare, but could cause major clinical sequelae and pose considerable diagnostic
      and therapeutic challenges. Here, we report the intraoperative application of
      real time three-dimensional transesophageal echocardiography (RT3DTEE) in the
      assessment of a patient with a RVOT myxoma. RT3DTEE clearly assess the
      characteristics of the mass, such as the size, shape, attachment points, and
      composition. With the intraoperative guidance of RT3DTEE, the patient underwent
      successful removal of the mass. 

PMID- 24724539
TI  - Solutions to the new threats to academic freedom?
AB  - In my commentary on Francesca Minerva's article 'New Threats to Academic
      Freedom', I agree with her contention that the existence of the Internet has
      given rise to new and very serious threats to academic freedom. I think that it
      is crucial that we confront those threats, and find ways to eliminate them, which
      I believe can be done. The threats in question involve both authors and editors.
      In the case of authors, I argue that the best solution is not anonymous
      publication, but publication using pseudonyms, and I describe how that would
      work. In the case of editors, my proposal is a website that a number of journals
      would have access to, where papers that editors judge to be clearly worthy of
      publication, but whose publication seems likely to set off a firestorm of public
      and media protest, could be published without any indication of the journal that
      had accepted the paper for publication.

PMID- 24724540
TI  - Against anonymity.
AB  - In 'New Threats to Academic Freedom' Francesca Minerva argues that anonymity for
      the authors of controversial articles is a prerequisite for academic freedom in
      the Internet age. This argument draws its intellectual and emotional power from
      the author's account of the reaction to the on-line publication of ' After-birth
      abortion: why should the baby live?'--an article that provoked cascades of
      hostile postings and e-mails. Reflecting on these events, Minerva proposes that
      publishers should offer the authors of controversial articles the option of
      publishing their articles anonymously. This response reviews the history of
      anonymous publication and concludes that its reintroduction in the Internet era
      would recreate problems similar to those that led print journals to abandon the
      practice: corruption of scholarly discourse by invective and hate speech, masked
      conflicts of interest, and a diminution of editorial accountability. It also
      contends that Minerva misreads the intent of the hostile e-mails provoked by
      'After-birth abortion,' and that ethicists who publish controversial articles
      should take responsibility by dialoguing with their critics--even those whose
      critiques are emotionally charged and hostile.

PMID- 24724541
TI  - Academic freedom, public reactions, and anonymity.
AB  - Academic freedom can be defined as immunity against adverse reactions from the
      general public, designed to keep scholars unintimidated and productive even after
      they have published controversial ideas. Francesca Minerva claims that this
      notion of strict instrumental academic freedom is supported by Ronald Dworkin,
      and that anonymity would effectively defend the sphere of immunity implied by it.
      Against this, I argue that the idea defended by Minerva finds no support in the
      work by Dworkin referred to; that anonymity would not in most cases effectively
      protect the kind of immunity sought after; and that in some cases it would not
      even be desirable to protect scholars from public reactions to their
      controversial claims. 

PMID- 24724542
TI  - Academic freedom and the professional responsibilities of applied ethicists: a
      comment on Minerva.
AB  - Academic freedom is an important good, but it comes with several
      responsibilities. In this commentary we seek to do two things. First, we argue
      against Francesca Minerva's view of academic freedom as presented in her article
      'New threats to academic freedom' on a number of grounds. We reject the nature of
      the absolutist moral claim to free speech for academics implicit in the article;
      we reject the elitist role for academics as truth-seekers explicit in her view;
      and we reject a possible more moderate re-construction of her view based on the
      harm/offence distinction. Second, we identify some of the responsibilities of
      applied ethicists, and illustrate how they recommend against allowing for
      anonymous publication of research. Such a proposal points to the wider perils of
      a public discourse which eschews the calm and careful discussion of ideas.

PMID- 24724543
TI  - Why publishing pseudonymously can protect academic freedom.

PMID- 24724544
TI  - Ethics of public health promotion messaging in the age of successful HIV
      treatment regimes.

PMID- 24724545
TI  - Altered N-Glycan expression profile in epithelial-to-mesenchymal transition of
      NMuMG cells revealed by an integrated strategy using mass spectrometry and
      glycogene and lectin microarray analysis.
AB  - Epithelial-to-mesenchymal transition (EMT) is an essential biological process
      that occurs in embryonic development, metastatic diseases, and cancer
      progression. Altered expression of glycans is known to be associated with cancer
      progression. No studies to date have presented global analysis of the precise
      variation of N-glycans in EMT. We describe here the profile of N-glycans and
      glycogene expression in the EMT process induced by transforming growth factor
      beta1 (TGFbeta1) in a normal mouse mammary gland epithelial (NMuMG) cell model.
      An integrated strategy with a combination of mass spectrometry, glycogene
      microarray analysis, and lectin microarray analysis was applied, and results were
      confirmed by lectin histochemistry and quantitative real-time PCR. In TGFbeta
      induced EMT, levels of high-mannose-type N-glycans were enhanced, antennary N
      glycans, and fucosylation were suppressed, and bisecting GlcNAc N-glycans were
      greatly suppressed. The expression of seven N-glycan-related genes was
      significantly changed. The products of glycogenes ALG9, MGAT3, and MGAT4B
      appeared to contribute to the observed alteration of N-glycans. The findings
      indicate that dysregulation of N-glycan synthesis plays a role in the EMT
      process. Systematic glycomic analysis based on the combination of techniques
      described here is expected to facilitate the discovery of the aberrant N
      glycosylation in tumor progression and provide essential information in systems
      glycobiology. 

PMID- 24724546
TI  - Tumour-to-tumour metastasis of lung adenocarcinoma to ovarian serous cystadenoma.

PMID- 24724547
TI  - Functional equivalence of grasping cerci and nuptial food gifts in promoting
      ejaculate transfer in katydids.
AB  - The function of nuptial gifts has generated longstanding debate. Nuptial gifts
      consumed during ejaculate transfer may allow males to transfer more ejaculate
      than is optimal for females. However, gifts may simultaneously represent male
      investment in offspring. Evolutionary loss of nuptial gifts can help elucidate
      pressures driving their evolution. In most katydids (Orthoptera: Tettigoniidae),
      males transfer a spermatophore comprising two parts: the ejaculate-containing
      ampulla and the spermatophylax-a gelatinous gift that females eat during
      ejaculate transfer. Many species, however, have reduced or no spermatophylaces
      and many have prolonged copulation. Across 44 katydid species, we tested whether
      spermatophylaces and prolonged copulation following spermatophore transfer are
      alternative adaptations to protect the ejaculate. We also tested whether
      prolonged copulation was associated with (i) male cercal adaptations, helping
      prevent female disengagement, and (ii) female resistance behavior. As predicted,
      prolonged copulation following (but not before) spermatophore transfer was
      associated with reduced nuptial gifts, differences in the functional morphology
      of male cerci, and behavioral resistance by females during copulation.
      Furthermore, longer copulation following spermatophore transfer was associated
      with larger ejaculates, across species with reduced nuptial gifts. Our results
      demonstrate that nuptial gifts and the use of grasping cerci to prolong ejaculate
      transfer are functionally equivalent. 

PMID- 24724549
TI  - Acute toxicity of chlorpyrifos to the non-target organism Cnesterodon
      decemmaculatus.
AB  - Chlorpyrifos is the most used insecticide in Argentina. Cnesterodon
      decemmaculatus is a widely distributed, endemic fish from Neotropical America. It
      attains high densities in the shallow water assemblages of Argentina and Brazil.
      The aim of this study was to assess the acute toxicity of chlorpyrifos to C.
      decemmaculatus. The mean 96-h LC50 of three independent determinations was 105.3
      (+/- 3.1) MUg/L. Sublethal effects were observed. Swimming behavioral changes at
      each chlorpyrifos exposure concentration were reported. C. decemmaculatus
      represents a good model for ecotoxicological risk assessment.

PMID- 24724550
TI  - Family satisfaction following spinal fusion in Rett syndrome.
AB  - PURPOSE: We evaluated family satisfaction following spinal fusion in girls with
      Rett syndrome. METHODS: Families participating in the population-based and
      longitudinal Australian Rett Syndrome Database whose daughter had undergone
      spinal fusion provided data on satisfaction overall, care processes and expected
      changes in health and function. Content analysis of responses to open-ended
      questions was conducted. RESULTS: Families reported high levels of overall
      satisfaction and consistently high ratings in relation to surgical and ICU care.
      Outstanding clinical care and the development of strong partnerships with
      clinical staff were much appreciated by families, whereas poor information
      exchange and inconsistent care caused concerns. CONCLUSIONS: Family satisfaction
      is an important outcome within a patient-centred quality of care framework. Our
      findings suggest strategies to inform the delivery of care in relation to spinal
      fusion for Rett syndrome and could also inform the hospital care of other
      children with disability and a high risk of hospitalization.

PMID- 24724551
TI  - Activation of sperm EGFR by light irradiation is mediated by reactive oxygen
      species.
AB  - To acquire fertilization competence, spermatozoa must undergo several biochemical
      and motility changes in the female reproductive tract, collectively called
      capacitation. Actin polymerization and the development of hyperactivated motility
      (HAM) are part of the capacitation process. In a recent study, we showed that
      irradiation of human sperm with visible light stimulates HAM through a mechanism
      involving reactive-oxygen-species (ROS), Ca(2+) influx, protein kinases A (PKA),
      and sarcoma protein kinase (Src). Here, we showed that this effect of light on
      HAM is mediated by ROS-dependent activation of the epidermal growth factor
      receptor (EGFR). Interestingly, ROS-mediated HAM even when the EGFR was activated
      by EGF, the physiological ligand of EGFR. Light irradiation stimulated ROS
      dependent actin polymerization, and this effect was abrogated by PBP10, a peptide
      which activates the actin-severing protein, gelsolin, and causes actin
      depolymerization in human sperm. Light-stimulated tyrosine phosphorylation of Src
      dependent gelsolin, resulting in enhanced HAM. Thus, light irradiation stimulates
      HAM through a mechanism involving Src-mediated actin polymerization. Light
      stimulated HAM and in vitro-fertilization (IVF) rate in mouse sperm, and these
      effects were mediated by ROS and EGFR. In conclusion, we show here that
      irradiation of sperm with visible light, enhances their fertilization capacity
      via a mechanism requiring ROS, EGFR and HAM. 

PMID- 24724552
TI  - Separation and purification of small peptides from fermented sesame meal and
      their antioxidant activities.
AB  - Protein hydrolysates are widely applied as antioxidants in nutrition, but the
      potential antioxidant activities of small peptides remain unknown. Therefore, we
      investigated the antioxidant activities of small peptides isolated from solid
      state fermented sesame meal via Sephadex G-15 chromotography. The scavenging
      capacities for 2, 2- diphenylpicrylhydrazyl (DPPH) and hydroxyl (*OH) radicals as
      well as the total reducing capacity were determined. The in vivo antioxidant
      activity was determined upon 30-d intragastric administration of the isolated
      small peptides (tripeptide, tetrapeptide, and hexapeptide) at different doses
      (0.1, 0.2, and 0.4 g/kg*d) in healthy Kunming mice. The results showed that the
      DPPH and *OH scavenging rates of the three peptides exceeded 80%. The total
      reducing activities of 4 mg/mL tetrapeptide or hexapeptide and 2 mg/mL tripeptide
      were comparable to that of 0.5 mg/mL glutathione. In mice fed sesame peptides,
      malondialdehyde levels in the serum and liver were lower than those in controls,
      whereas the activities of liver superoxide dismutase and glutathione peroxidase
      were significantly higher than those in controls (P<0.05). The antioxidant
      activity of tripeptide was significantly higher than those of tetrapeptide and
      hexapeptide (P<0.05). In conclusion, small peptides extracted from solid-state
      fermented sesame meal possess strong antioxidant activities that increase with
      decreasing peptide molecular weight. 

PMID- 24724553
TI  - Optimization of surfactin production by Bacillus subtilis HSO121 through Plackett
      Burman and response surface method.
AB  - Bacillus subtilis HSO121 was previously isolated from the formation water of an
      oil field and found to produce surfactin lipopeptides. Effects of 10 different
      components on surfactin production have been studied by Plackett- Burman design
      (PBD). Each component was screened on the basis of P-value, which was at 92% or
      above of confidence level. In PBD, significant factors influencing the surfactin
      production were selected for further optimization via response surface
      methodology approach (RSM). Four significant variables (calcium chloride, ferrous
      sulfate, maltose, and L-arginine) were selected for the optimization studies, and
      constructed via central composite design (CCD). Calcium chloride, maltose and L
      arginine showed a significant positive effect on surfactin production, while
      ferrous sulfate had no significant effect. An overall 38.06-fold increase in
      surfactin production yield was achieved in the optimized medium as compared with
      the unoptimized basal medium. Surfactin production yield increased significantly
      with optimized medium (47.58 g/l) when compared with the unoptimized one (1.25
      g/l). 

PMID- 24724555
TI  - Dipping your feet in the water: podocytes in urine.
AB  - Podocyte injury and loss plays an important role in the pathogenesis and
      progression of many kidney diseases. Studies have shown that podocyte-related
      markers and products can be detected in the urine of patients with glomerular
      diseases such as focal segmental glomerulosclerosis, IgA nephropathy, lupus
      nephritis, diabetic nephropathy and pre-eclampsia. Therefore, detecting the loss
      of podocytes in the urine provides a useful noninvasive technique of gathering
      information about the disease type and/or activity of glomerular diseases.
      Currently, urine podocyte-related protein markers, mRNA, microRNA and exosomes
      have been used with varying degrees of success to study glomerular diseases. The
      determination of urinary podocyte loss may become an important noninvasive tool
      in the evaluation of glomerular diseases.

PMID- 24724556
TI  - Effect of collagen nanotopography on keloid fibroblast proliferation and matrix
      synthesis: implications for dermal wound healing.
AB  - Keloids are locally exuberant dermal scars characterized by excessive fibroblast
      proliferation and matrix accumulation. Although treatment strategies include
      surgical removal and intralesional steroid injections, an effective regimen is
      yet to be established due to a high rate of recurrence. The regressing center and
      growing margin of the keloid have different collagen architecture and also differ
      in the rate of proliferation. To investigate whether proliferation is responsive
      to collagen topography, keloid, scar, and dermal fibroblasts were cultured on
      nanopatterned scaffolds varying in collagen fibril diameter and alignment-small
      and large diameter, aligned and random fibrils, and compared to cells grown on
      flat collagen-coated substrates, respectively. Cell morphology, proliferation,
      and expression of six genes related to proliferation (cyclin D1), phenotype
      (alpha-smooth muscle actin), and matrix synthesis (collagens I and III, and
      matrix metalloproteinase-1 and -2) were measured to evaluate cell response.
      Fibril alignment was shown to reduce proliferation and matrix synthesis in all
      three types of fibroblasts. Further, keloid cells were found to be most
      responsive to nanotopography. 

PMID- 24724557
TI  - Fibroblast growth factor 21 and its relation to metabolic parameters in women
      with polycystic ovary syndrome.
AB  - OBJECTIVE: The aim of this study was to compare the serum levels of fibroblast
      growth factor 21 (FGF-21) between patients with polycystic ovary syndrome (PCOS)
      and control subjects and to assess the possible relation with the hormonal and
      metabolic parameters. METHODS: A total of 91 patients with PCOS and 53 age- and
      body mass index (BMI)-matched healthy controls were included in the study. We
      evaluated anthropometric, hormonal and metabolic parameters in all the cases.
      Serum FGF-21 and high sensitive C-reactive protein (hsCRP) levels were measured
      by ELISA. RESULTS: Mean fasting glucose and insulin, homeostasis model assessment
      insulin resistance index (HOMA-IR), triglyceride, total cholesterol, low density
      lipoprotein cholesterol, total testosterone, dehydroepiandrosterone sulfate
      (DHEAS) levels were significantly higher in PCOS patients. Serum FGF-21 levels
      were similar in PCOS (236.8 +/- 171.2 pg/ml) and the control (224.6 +/- 128.9
      pg/ml) group (p = 0.654). FGF-21 level had no correlation with BMI, waist
      circumference, HOMA-IR, hsCRP and lipid parameters. However there was a
      significant negative correlation between FGF-21 and DHEAS levels (r = - 0.309, p
      = 0.003). CONCLUSION: FGF-21 levels were similar in women with PCOS compared with
      those of age- and BMI- matched controls.

PMID- 24724558
TI  - Torsioned extraovarian thecoma.

PMID- 24724559
TI  - Comparison of a direct and an indirect approach for the functional assessment of
      insistence on sameness in a child with autism spectrum disorder and a typically
      developing child.
AB  - OBJECTIVE: To compare indirect and direct functional assessment of insistence on
      sameness associated with autism spectrum disorder (ASD) and typical development.
      METHODS: Parents rated the function of insistence on sameness for a 6-year-old
      boy with ASD (Peter) and a typically developing 4-year-old boy (Nathan) using the
      Motivation Assessment Scale (MAS). Ratings were compared to the results of a
      direct assessment. RESULTS: The results of the assessment procedures were mainly
      consistent for Peter and suggested that his tendency to insist on sameness was
      maintained by sensory consequences. The finding of an attention function for
      Nathan in the play-based assessment was consistent with previous functional
      assessment studies surrounding typically developing children, but in contrast to
      the MAS. CONCLUSION: While the play-based assessment may be more suitable for
      assessing the high rate insistence on sameness observed in individuals with ASD,
      the MAS may be more suitable for low rate insistence on sameness.

PMID- 24724560
TI  - Synthesis of substituted tetrahydroindoloisoquinoline derivatives via
      intramolecular Pd-catalyzed alkene carboamination reactions.
AB  - Intramolecular Pd-catalyzed alkene carboamination reactions of substituted 2
      allyl-N-(2-bromobenzyl)anilines are described. The substrates for these reactions
      are generated in two steps from readily available 2-allylanilines and 2
      bromobenzaldehyde derivatives. The transformations afford substituted
      tetrahydroindoloisoquinolines, an uncommon class of fused bicyclic heterocycles,
      in good yield. The mechanism of these transformations is described, and a model
      that accounts for the observed product stereochemistry is proposed. 

PMID- 24724561
TI  - Direct linkage between dimethyl sulfide production and microzooplankton grazing,
      resulting from prey composition change under high partial pressure of carbon
      dioxide conditions.
AB  - Oceanic dimethyl sulfide (DMS) is the enzymatic cleavage product of the algal
      metabolite dimethylsulfoniopropionate (DMSP) and is the most abundant form of
      sulfur released into the atmosphere. To investigate the effects of two emerging
      environmental threats (ocean acidification and warming) on marine DMS production,
      we performed a large-scale perturbation experiment in a coastal environment. At
      both ambient temperature and ~ 2  degrees C warmer, an increase in partial
      pressure of carbon dioxide (pCO2) in seawater (160-830 ppmv pCO2) favored the
      growth of large diatoms, which outcompeted other phytoplankton species in a
      natural phytoplankton assemblage and reduced the growth rate of smaller, DMSP
      rich phototrophic dinoflagellates. This decreased the grazing rate of
      heterotrophic dinoflagellates (ubiquitous micrograzers), resulting in reduced DMS
      production via grazing activity. Both the magnitude and sign of the effect of
      pCO2 on possible future oceanic DMS production were strongly linked to pCO2
      induced alterations to the phytoplankton community and the cellular DMSP content
      of the dominant species and its association with micrograzers.

PMID- 24724562
TI  - Passive lipoidal diffusion and carrier-mediated cell uptake are both important
      mechanisms of membrane permeation in drug disposition.
AB  - Recently, it has been proposed that drug permeation is essentially carrier
      mediated only and that passive lipoidal diffusion is negligible. This opposes the
      prevailing hypothesis of drug permeation through biological membranes, which
      integrates the contribution of multiple permeation mechanisms, including both
      carrier-mediated and passive lipoidal diffusion, depending on the compound's
      properties, membrane properties, and solution properties. The prevailing
      hypothesis of drug permeation continues to be successful for application and
      prediction in drug development. Proponents of the carrier-mediated only concept
      argue against passive lipoidal diffusion. However, the arguments are not
      supported by broad pharmaceutics literature. The carrier-mediated only concept
      lacks substantial supporting evidence and successful applications in drug
      development.

PMID- 24724563
TI  - High-resolution melting assay for genotyping of IFNL4-associated dinucleotide
      variant rs368234815.
AB  - Interferon-lambda4-related dinucleotide variant rs368234815 TT/-G is strongly
      linked with rs12979860 polymorphism, the most important genetic marker connected
      to treatment-induced hepatitis C virus clearance. Due to additional baseline
      information that rs368234815 polymorphism could provide for the management of
      chronic hepatitis C, we developed and validated a high-resolution melting
      genotyping assay using 193 patients with chronic hepatitis C. 

PMID- 24724564
TI  - Structural insights into the T6SS effector protein Tse3 and the Tse3-Tsi3 complex
      from Pseudomonas aeruginosa reveal a calcium-dependent membrane-binding
      mechanism.
AB  - The opportunistic pathogen Pseudomonas aeruginosa uses the type VI secretion
      system (T6SS) to deliver the muramidase Tse3 into the periplasm of rival bacteria
      to degrade their peptidoglycan (PG). Concomitantly, P. aeruginosa uses the
      periplasm-localized immunity protein Tsi3 to prevent potential self-intoxication
      caused by Tse3, and thus gains an edge over rival bacteria in fierce niche
      competition. Here, we report the crystal structures of Tse3 and the Tse3-Tsi3
      complex. Tse3 contains an annexin repeat-like fold at the N-terminus and a G-type
      lysozyme fold at the C-terminus. One loop in the N-terminal domain (Loop 12) and
      one helix (alpha9) from the C-terminal domain together anchor Tse3 and the Tse3
      Tsi3 complex to membrane in a calcium-dependent manner in vitro, and this
      membrane-binding ability is essential for Tse3's activity. In the C-terminal
      domain, a Y-shaped groove present on the surface likely serves as the PG binding
      site. Two calcium-binding motifs are also observed in the groove and these are
      necessary for Tse3 activity. In the Tse3-Tsi3 structure, three loops of Tsi3
      insert into the substrate-binding groove of Tse3, and three calcium ions present
      at the interface of the complex are indispensable for the formation of the Tse3
      Tsi3 complex.

PMID- 24724565
TI  - Canine soft tissue sarcoma managed in first opinion practice: outcome in 350
      cases.
AB  - OBJECTIVE: To determine outcome of dogs with a diagnosis of soft tissue sarcoma
      managed in first opinion practice. STUDY DESIGN: Retrospective, case-controlled
      study ANIMALS: Dogs (n = 350) with primary occurrence of a soft tissue sarcoma.
      METHODS: A previously validated questionnaire was sent to all veterinarians
      requesting clinical information and ultimate outcome for all dogs. Histologic
      sections were reviewed by a single pathologist. RESULTS: Most surgeries were
      unplanned, with only 15 (4%) dogs having a histologic and 59 (16.8%) dogs having
      a cytologic diagnosis before surgery. Median survival time for all dogs was not
      reached with 70% proportional survival at 5 years. Local recurrence developed in
      73 (20.8%) cases. The extent of resection performed was not associated with
      improved survival (P = .2) or tumor recurrence (P = .8). Age <8 years (chi(2)  =
      6.1; P = .01), tumors <5 cm in size (chi(2)  = 9.6; P = .002) and discrete tumors
      (chi(2)  = 16.6; P < .001) had improved survival outcomes. On multivariate
      analysis, a high tumor grade was significant for recurrence (HR 5.8; P < .001;
      95% CI: 2.2-14.8). Evidence of a selection bias towards less aggressive tumors
      being managed in first opinion practice was confirmed. CONCLUSIONS: Wide
      resection margins are not the primary determinant of outcome for all soft tissue
      sarcoma. Veterinarians need to better understand the biologic behavior of a
      suspected soft tissue sarcoma before treatment to allow surgical margins to be
      adjusted accordingly.

PMID- 24724567
TI  - An evaluation of classification algorithms for manual material handling tasks
      based on data obtained using wearable technologies.
AB  - With recent progress in wearable measurement systems, physical exposures can be
      feasibly assessed at high precision in the workplace. Such systems, however,
      generally lack contextual information for a given job (e.g., task type,
      duration). To extract such information, we explored three classification
      algorithms to classify manual material handling (MMH) tasks during a simulated
      job in a laboratory, using several combinations of outputs from commercially
      available inertial motion capture and in-shoe pressure measurement systems. A
      total of 10 participants completed three replications of four cycles of a
      simulated job. Precision and recall values of >= ~90% and 80%, respectively, and
      errors in estimated task duration of < ~14%, could be achieved across the MMH
      task examined. Classification performance, however, varied between classification
      algorithms, input data sets and task types. Overall, combining wearable
      technology with task classification could be an effective approach for field
      based exposure assessment, though field-testing is needed to demonstrate the
      applicability of this method. PRACTITIONER SUMMARY: Combining wearable
      technologies with task classification was explored to extract exposure context,
      specifically task type and duration. Results supported that task classification
      can facilitate the use of wearable technologies in field-based exposure
      assessment, specifically by aiding in task identification from within the rather
      large data sets obtained from these technologies.

PMID- 24724568
TI  - The additional value of three-dimensional transesophageal echocardiography in
      complex aortic prosthetic heart valve endocarditis.
AB  - BACKGROUND: Two-dimensional transthoracic and transesophageal echocardiography
      (2DTTE and 2DTEE) may fail to detect signs of prosthetic heart valve (PHV)
      endocarditis due to acoustic shadowing. Three-dimensional (3D) TEE may have
      additional value; however, data are scarce. This study was performed to
      investigate the additional value of 3DTEE for the detection of aortic PHV
      endocarditis and the extent of the disease process. METHODS: Retrospective
      analysis of complex aortic PHV endocarditis cases that underwent 2DTTE, 2DTEE,
      and 3DTEE before surgery. Echocardiograms were individually assessed by 2
      cardiologists blinded for the outcome. Surgical and pathological inspection
      served as the reference standard for vegetations and peri-annular extensions
      (abscesses/mycotic aneurysms). To determine if the proximal coronary arteries
      were involved in the inflammatory process as well, computed tomography
      angiography findings were added to reference standard. RESULTS: Fifteen aortic
      PHV endocarditis cases were identified. According to the reference standard, all
      15 cases had peri-annular extensions, 13 of which had a close relationship with
      the proximal right and/or left coronary artery. In 6 of 15 patients, a vegetation
      was present. Combined 2DTTE/TEE missed 1/6 vegetations and 1/15 peri-annular
      extensions. After addition of 3DTEE, all vegetations (6/6) and peri-annular
      extensions (15/15) were detected, without adding false positives. Compared to
      2DTEE, in 3/15 cases, 3DTEE resulted in better delineation of the anatomical
      relationship of the proximal coronary arteries to the peri-annular extensions. As
      a result, 3DTEE had an additional value in 5/15 cases. CONCLUSION: In complex
      aortic, PHV endocarditis 3DTEE may have additional value compared to 2D
      echocardiography.

PMID- 24724569
TI  - Methyl-aminolevulinic acid photodynamic therapy for actinic keratoses: a useful
      treatment or a risk factor? A retrospective study.
AB  - INTRODUCTION: Photodynamic therapy (PDT) is a non-invasive treatment, used for
      superficial non-melanoma skin cancer (NMSC) and actinic keratoses (AKs). Although
      PDT is considered a safe treatment, some authors report that PDT may have
      carcinogenic risks. We undertook this retrospective study to determine if there
      is a real risk of carcinogenicity for patients treated with MAL-PDT for AK and
      which risk factors may increase the rate of the malignant transformation.
      METHODS: We reviewed the records of patients treated with PDT for one or more AKs
      at the Sant'Orsola-Malpighi Hospital from January 2010 to December 2012. We also
      considered if patients had one or more risk factors for NMSC. RESULTS: Three
      hundred fifty-seven patients were treated with PDT for AKs, among them 17
      patients developed a squamous cell carcinoma (SCC) in the site of a lesion
      previously treated with PDT. Comparing these two groups, the group which
      developed the SCC presented more risk factors for NMSC. CONCLUSION: PDT is
      certainly a good method to treat AKs, but it is important also to consider all
      its side effects. Among them, the carcinogenetic risk is still underestimated. We
      suggest that patients with multiple risk factors for NMSC treated with PDT should
      undergo more frequent follow-ups, in order to prevent malignant progression.

PMID- 24724570
TI  - Two types of T wave alternans in long-QT syndrome.

PMID- 24724571
TI  - Equilibrium thermodynamics to form a rhodium formyl complex from reactions of CO
      and H2: metal sigma donor activation of CO.
AB  - A rhodium(II) dibenzotetramethylaza[14]annulene dimer ([(tmtaa)Rh]2) (1) reacts
      with CO and H2 in toluene and pyridine to form equilibrium distributions with
      hydride and formyl complexes ((tmtaa)Rh-H (2); (tmtaa)Rh-C(O)H (3)). The rhodium
      formyl complex ((tmtaa)Rh-C(O)H) was isolated under a CO/H2 atmosphere, and the
      molecular structure was determined by X-ray diffraction. Equilibrium constants
      were evaluated for reactions of (tmtaa)Rh-H with CO to produce formyl complexes
      in toluene (K2(298 K)(tol) = 10.8 (1.0) * 10(3)) and pyridine (K2(298 K)(py) =
      2.2 (0.2) * 10(3)). Reactions of 1 and 2 in toluene and pyridine are discussed in
      the context of alternative radical and ionic pathways. The five-coordinate 18
      electron Rh(I) complex ([(py)(tmtaa)Rh(I)](-)) is proposed to function as a
      nucleophile toward CO to give a two-electron activated bent Rh-CO unit. Results
      from DFT calculations on the (tmtaa)Rh system correlate well with experimental
      observations. Reactions of 1 with CO and H2 suggest metal catalyst design
      features to reduce the activation barriers for homogeneous CO hydrogenation. 

PMID- 24724572
TI  - Rapid loss of behavioral plasticity and immunocompetence under intense sexual
      selection.
AB  - Phenotypic plasticity allows animals to maximize fitness by conditionally
      expressing the phenotype best adapted to their environment. Although evidence for
      such adjustment in reproductive tactics is common, little is known about how
      phenotypic plasticity evolves in response to sexual selection. We examined the
      effect of sexual selection intensity on phenotypic plasticity in mating behavior
      using the beetle Callosobruchus maculatus. Male genital spines harm females
      during mating and females exhibit copulatory kicking, an apparent resistance
      trait aimed to dislodge mating males. After exposing individuals from male- and
      female-biased experimental evolution lines to male- and female-biased sociosexual
      environments, we examined behavioral plasticity in matings with standard
      partners. While females from female-biased lines kicked sooner after exposure to
      male-biased sociosexual contexts, in male-biased lines this plasticity was lost.
      Ejaculate size did not diverge in response to selection history, but males from
      both treatments exhibited plasticity consistent with sperm competition intensity
      models, reducing size as the number of competitors increased. Analysis of
      immunocompetence revealed reduced immunity in both sexes in male-biased lines,
      pointing to increased reproductive costs under high sexual selection. These
      results highlight how male and female reproductive strategies are shaped by
      interactions between phenotypically plastic and genetic mechanisms of sexual
      trait expression.

PMID- 24724573
TI  - Non-bladder conditions in female Taiwanese patients with interstitial
      cystitis/hypersensitive bladder syndrome.
AB  - OBJECTIVES: To detect non-bladder conditions in patients with interstitial
      cystitis/hypersensitive bladder syndrome. METHODS: A total of 122 female
      interstitial cystitis/hypersensitive bladder syndrome patients and a control
      group of 122 age-matched female patients with stress urinary incontinence
      completed screening questionnaires for irritable bowel syndrome,
      temporomandibular disorder, multiple chemical sensitivities, tension and migraine
      headache, localized myofascial pain disorder, and fibromyalgia. Interstitial
      cystitis/hypersensitive bladder syndrome patients also completed questionnaires
      on interstitial cystitis/hypersensitive bladder syndrome symptom severity,
      including the O'Leary-Sant symptom index, and the visual analog scale for pain
      and urgency. RESULTS: Interstitial cystitis/hypersensitive bladder syndrome
      patients were more likely to meet diagnostic criteria for irritable bowel
      syndrome than controls (37.5% vs 11.5%), and tension/migraine headache (38.7% vs
      15.7%; all P < 0.001). The prevalence of temporomandibular disorder, multiple
      chemical sensitivities, localized myofascial pain disorders and fibromyalgia did
      not reach a statistical significant difference between the two groups. In the
      multivariate model, associations were also observed for irritable bowel syndrome
      (odds ratio 2.546; 95% confidence interval 1.136-5.704) and tension/migraine
      headache (odds ratio 2.684; 95% confidence interval 1.233-5.842). Patients with
      more comorbid conditions had more severe and bothersome interstitial
      cystitis/hypersensitive bladder syndrome symptoms as measured by the visual
      analog scale of pain (P = 0.008) and O'Leary-Sant bother index (P = 0.035).
      CONCLUSIONS: Interstitial cystitis/hypersensitive bladder syndrome patients are
      more likely to have multiple non-bladder conditions. These conditions correlate
      with the severity of interstitial cystitis/hypersensitive bladder syndrome
      symptoms.

PMID- 24724574
TI  - Assessing the citrullinome in rheumatoid arthritis synovial fluid with and
      without enrichment of citrullinated peptides.
AB  - Protein citrullination is a posttranslational modification that has attracted
      increased attention, especially for its involvement in rheumatoid arthritis (RA).
      Here, we assess the citrullinome in RA synovial fluid by direct LC-MS/MS analysis
      and by the use of an enrichment strategy based on citrulline specific
      biotinylation. RA synovial fluid was depleted for abundant proteins, and total
      and depleted fractions were analyzed. Frequency of citrullinated peptides and
      their degree of citrullination could be determined for four known RA
      autoantigens, as well as a novel in vivo autocitrullination site of
      peptidylarginine deiminase 4. From the analysis of total and depleted synovial
      fluid after enrichment we could estimate the numbers of citrullinated peptides to
      be approximately 3600 and 2100, respectively. However, identification of these
      biotinylated peptides by MS/MS turned out to be very difficult due to
      fragmentation of the biotin moiety. By direct MS analysis of the total and
      depleted synovial fluid without enrichment, 119 and 157 citrullinated peptides
      were identified, respectively. This indicates that direct analysis allows
      identification of only a fraction of the citrullinated proteins present in
      synovial fluid and that specific enrichment is still needed for a comprehensive
      in-depth elucidation of the citrullinome. 

PMID- 24724575
TI  - Rhodium catalyzed direct arylation of alpha-diazoimines.
AB  - An efficient rhodium catalyzed direct arylation of alpha-diazoimines, generated
      from readily accessible 1,2,3-triazole, has been accomplished for the synthesis
      of 2,2-diaryl enamides. The reaction involves the chemo- and regioselective
      insertion of rhodium azavinyl carbene into aromatic C(sp(2))-H bonds. Utility of
      the developed methodology was demonstrated in the synthesis of indole and
      tetrahydroisoquinoline frameworks. 

PMID- 24724576
TI  - Effect of voriconazole and ultraviolet-A combination therapy compared to
      voriconazole single treatment on Fusarium solani fungal keratitis.
AB  - PURPOSE: To demonstrate that ultraviolet-A (UV-A) and voriconazole combination
      therapy is more effective than voriconazole single treatment for fungal
      keratitis. METHODS: The in vitro UV-A (375 nm) fungicidal effect was evaluated on
      Fusarium solani solutions. Each fungal solution was irradiated with different UV
      A irradiation doses. Also, a fungal solution containing voriconazole was also
      irradiated with UV-A. The in vivo therapeutic effect of UV-A and voriconazole
      treatment was studied in a rabbit keratitis model. Fungi were injected
      intrastromally into the cornea of 16 rabbits. Each treatment was initiated 3 days
      after fungal injection and continued up to 8 days for the following groups: Group
      1, control; Group 2, treated with UV-A once a day; Group 3, treated with
      voriconazole 3 times a day; Group 4, treated with voriconazole 3 times a day and
      UV-A once a day. On the last day, the sclera-cornea buttons were extracted and
      microbiological and histological evaluations were performed. RESULTS: The colony
      forming units (CFUs) of fungal solutions in culture significantly decreased with
      UV-A irradiation. The CFUs of fungal solutions containing voriconazole also
      decreased with UV-A irradiation. In vivo, clinical scores of Group 3 (P=0.03) and
      Group 4 (P=0.02) 5 days after treatment were significantly lower compared to that
      of Group 1. The clinical score of Group 4 (P=0.03) 5 days after treatment was
      significantly lower compared to that of Group 3. The histopathological scores 5
      days after treatment were significantly lower in Group 4 compared to those of
      Group 1 (P<0.01) and Group 3 (P=0.02). Based on our CFU analysis, only Group 4
      showed significantly lower CFUs compared to Group 1 (P=0.04). CONCLUSIONS: UV-A
      and voriconazole combination treatment could be a safe and effective alternative
      to voriconazole single treatment for fungal keratitis.

PMID- 24724577
TI  - The influence of coagulation factors on the in-treatment biological variation of
      international normalized ratio for patients on warfarin.
AB  - BACKGROUND: Biological variation is usually estimated in healthy individuals
      during steady-state conditions. The aim of this study was to estimate the in
      treatment biological variation of the International normalised ratio (INR) and to
      investigate to what extent the different levels of coagulation factors could
      explain this variation. METHODS: Blood samples were collected from randomly
      included patients on warfarin treatment. INR was determined on a laboratory
      instrument (STA Compact((r))) and on three point-of-care instruments (Simple
      Simon((r))PT, CoaguChek((r))XS and INRatio(TM)). The level of fibrinogen, and the
      activity of coagulation factors II, V, VII and X were determined. RESULTS: The in
      treatment within- and between-subject coefficients of variation of INR were
      dependent on the method and varied between 18 and 24% and 13 and 19%,
      respectively, and were reduced to 3.9-5.1% and 2.3-5.8%, after correction for
      coagulation factors which could explain 91-95% of the variance of INR.
      CONCLUSIONS: The in-treatment biological variation of INR was higher than
      reported for healthy individuals as well as patients in a steady-state condition,
      but by correcting for appropriate coagulation factors it was reduced. The
      association between INR and coagulation factors was different for the different
      PT methods mainly due to different sensitivity towards FII and FVII.

PMID- 24724578
TI  - Stability of HE4 and CA125 in blood samples from patients diagnosed with ovarian
      cancer.
AB  - OBJECTIVE: To investigate the influence of handling and storage on HE4 and CA125
      serum and EDTA plasma levels to clarify any important consequences for a clinical
      setting. METHODS: Blood samples from 13 ovarian cancer (OC) patients were
      collected and allowed to clot or sediment for up to 72 hours at 4  degrees C or
      20  degrees C, then processed into serum and EDTA plasma. Furthermore, the
      effects of up to eight repetitive cycles of freeze/thaw were investigated. HE4
      and CA125 were analyzed using a Chemiluminescent Microparticle Immunoassay on the
      Architect i2000sr System. RESULTS: No significant effect of processing time for
      HE4 could be shown. HE4 EDTA plasma levels were insignificantly lower (3%) than
      serum levels (p = 0.41). Similarly, no significant effect of processing time for
      CA125 could be demonstrated. CA125 levels at 4  degrees C were significantly
      reduced compared to levels at 20  degrees C (p = 0.024). No significant
      difference between CA125 serum and plasma levels were found (p = 0.46). Serum and
      EDTA plasma samples were stable during the eight cycles of freezing and thawing
      (CA125: all p > 0.2; HE4: all p > 0.5). CONCLUSION: No systematic difference
      could be demonstrated for HE4. CA125 is not dependent on processing time, EDTA
      plasma or serum. Levels of CA125 are significantly reduced at 4  degrees C
      compared to levels at 20 degrees C, but this difference was less than 6% and is
      not considered clinically relevant.

PMID- 24724579
TI  - An interlaboratory comparison between similar methods for determination of
      melatonin, cortisol and testosterone in saliva.
AB  - An interlaboratory comparison study for melatonin, cortisol and testosterone in
      saliva in which five laboratories participated is reported in this study. Each
      laboratory blindly measured eight samples prepared from natural saliva spiked
      with melatonin, cortisol and testosterone in the range 0-579 pmol/L for
      melatonin, 0-90 nmol/L for cortisol, and 0-622 pmol/L for testosterone. The
      recovery of spiked material for melatonin ranged from 91-110%, from 83-100% for
      cortisol and from 80-94% for testosterone. The content of natural hormone in
      saliva was estimated to be between 0.278 and 6.90 pmol/L for melatonin, 0.56 and
      6.72 nmol/L for cortisol and 11.9 and 73.8 pmol/L for testosterone. This
      indicates a large interlaboratory variation. The present study emphasizes the
      importance of external quality control for the analysis of melatonin, cortisol
      and testosterone in saliva.

PMID- 24724580
TI  - Measuring systolic ankle and toe pressure using the strain gauge technique--a
      comparison study between mercury and indium-gallium strain gauges.
AB  - BACKGROUND: Measurement of the ankle and toe pressures are often performed using
      a plethysmograph, compression cuffs and a strain gauge. Usually, the strain gauge
      contains mercury but other alternatives exist. From 2014, the mercury-containing
      strain gauge will no longer be available in the European Union. The aim of this
      study was to compare an indium-gallium strain gauge to the established mercury
      containing strain gauge. METHODS: Consecutive patients referred to the Department
      of Clinical Physiology and Nuclear Medicine at Bispebjerg and Frederiksberg
      Hospitals for measurements of systolic ankle and toe pressures volunteered for
      the study. Ankle and toe pressures were measured twice with the mercury and the
      indium-gallium strain gauge in random order. Comparison of the correlation
      between the mean pressure using the mercury and the indium-gallium device and the
      difference between the two devices was performed for both toe and ankle level.
      RESULTS: A total of 53 patients were included (36 male). Mean age was 69 (range,
      45-92 years). Mean pressures at toe and ankle level with the mercury and the
      indium-gallium strain gauges were 77 (range, 0-180) mm Hg and 113 (range, 15-190)
      mm Hg, respectively. Comparison between the mercury and the indium-gallium strain
      gauge showed a difference in toe blood pressure values of - 0.7 mm Hg (SD: 7.0).
      At the ankle level, a difference of 2.0 mm Hg (SD: 8.6) was found. CONCLUSION:
      The two different devices agree sufficiently in the measurements of systolic
      ankle and toe pressure for the indium-gallium strain gauge to replace the mercury
      strain gauge.

PMID- 24724581
TI  - EPH receptor/ephrin system: in the quest for novel anti-angiogenic therapies:
      Commentary on Hassan-Mohamed et al., Br J Pharmacol 171: 5195-5208.
AB  - LINKED ARTICLE: This article is a Commentary on Hassan-Mohamed I, Giorgio C,
      Incerti M, Russo S, Pala D, Pasquale EB, Zanotti I, Vicini P, Barocelli E, Rivara
      S, Mor M, Lodola A and Tognolini M (2014). UniPR129 is a competitive small
      molecule Eph-ephrin antagonist blocking in vitro angiogenesis at low micromolar
      concentrations. Br J Pharmacol 171: 5195-5208. doi: 10.1111/bph.12669.

PMID- 24724582
TI  - HINARI grows: one step closer to health information for all.

PMID- 24724583
TI  - Computational study on the vinyl azide decomposition.
AB  - The decomposition mechanism of vinyl azide (CH2CHN3) has been studied by
      calculations of the electronic structure. In addition, a study based on the
      topology of the electron charge density distribution and its Laplacian function,
      within the Quantum Theory of Atoms in Molecules (QTAIM), has been carried out
      with the aim of comprehending the electron redistribution mechanisms that take
      place in the formation of vinyl nitrenes. The electronic structure calculations
      reveal that the decomposition of the s-cis conformer of vinyl azide leads to the
      formation of ketenimine through a single-step conversion, s-cis-CH2CHN3 -> CH2CNH
      + N2, while the conversion of the s-trans conformer to acetonitrile occurs in two
      steps, s-trans-CH2CHN3 -> cyc-CH2NCH + N2 -> CH3CN + N2. The topological analysis
      of the L(r) function reveals that triplet vinyl nitrene has one lone pair on the
      valence shell charge concentration (VSCC) of nitrogen and thus could act as a
      monodentate Lewis base, while singlet vinyl nitrene has two lone pairs on the
      VSCC of nitrogen and thus could act as a bidentate Lewis base. 

PMID- 24724584
TI  - Treatment of insulin resistance in the neurodegeneration.
AB  - The association between diabetes and neurodegenerative diseases is increasing
      with aging. Several common mechanisms are involved in both these diseases. The
      endothelial cells of the blood brain barrier, neurons and glia express typical
      and different receptors of the glucose metabolism (glucose transporters, insulin
      receptors and glucagon-like peptide-1 receptors). The impairment in insulin
      signaling leads to an impairment of neuronal function and increases
      neurodegeneration, and, conversely, neurodegeneration causes a reduction of
      insulin signaling on neurons. Increased detailed knowledge of common
      physiological processes opens up the opportunities for developing new treatments
      that may prevent or reduce the onset of neurodegenerative diseases. The aim of
      the review is to discuss the potential neuroprotective effects of the
      antidiabetic drugs. The article presents some promising patents on the treatment
      of insulin resistance in the neurodegeneration.

PMID- 24724585
TI  - A quantitative microbiological risk assessment for Campylobacter in petting zoos.
AB  - The significance of petting zoos for transmission of Campylobacter to humans and
      the effect of interventions were estimated. A stochastic QMRA model simulating a
      child or adult visiting a Dutch petting zoo was built. The model describes the
      transmission of Campylobacter in animal feces from the various animal species,
      fences, and the playground to ingestion by visitors through touching these so
      called carriers and subsequently touching their lips. Extensive field and
      laboratory research was done to fulfill data needs. Fecal contamination on all
      carriers was measured by swabbing in 10 petting zoos, using Escherichia coli as
      an indicator. Carrier-hand and hand-lip touching frequencies were estimated by,
      in total, 13 days of observations of visitors by two observers at two petting
      zoos. The transmission from carrier to hand and from hand to lip by touching was
      measured using preapplied cow feces to which E. coli WG5 was added as an
      indicator. Via a Beta-Poisson dose-response function, the number of Campylobacter
      cases for the whole of the Netherlands (16 million population) in a year was
      estimated at 187 and 52 for children and adults, respectively, so 239 in total.
      This is significantly lower than previous QMRA results on chicken fillet and
      drinking water consumption. Scenarios of 90% reduction of the contamination
      (meant to mimic cleaning) of all fences and just goat fences reduces the number
      of cases by 82% and 75%, respectively. The model can easily be adapted for other
      fecally transmitted pathogens. 

PMID- 24724586
TI  - Nucleic acid detection technologies and marker molecules in bacterial
      diagnostics.
AB  - There is a growing need for quick and reliable methods for microorganism
      detection and identification worldwide. Although traditional culture-based
      technologies are trustworthy and accurate at a relatively low cost, they are also
      time- and labor-consuming and are limited to culturable bacteria. Those
      weaknesses have created a necessity for alternative technologies that are capable
      for faster and more precise bacterial identification from medical, food or
      environmental samples. The most common current approach is to analyze the nucleic
      acid component of analyte solution and determine the bacterial composition
      according to the specific nucleic acid profiles that are present. This review
      aims to give an up-to-date overview of different nucleic acid target sequences
      and respective analytical technologies.

PMID- 24724587
TI  - Effects of robotic therapy on upper-extremity function in children with cerebral
      palsy: A systematic review.
AB  - OBJECTIVE: To systematically examine the effects of robotic therapy on upper
      extremity (UE) function in children with cerebral palsy (CP). METHODS: A
      systematic literature search was conducted in Pubmed, CINAHL, Cochrane,
      PsychInfo, TRIP, and Web of Science up to July 2013. Studies of children with CP,
      using robotic therapy and measures of UE were included. RESULTS: Nine articles
      using three different robotic systems were included. Of these, seven were case
      studies. Overall, robotic therapy showed the potential effects as all studies
      reported at least one positive outcome: a moderate effect in improving reaching
      duration, smoothness, or decreased muscle tone, and a small to large effect in
      standardized clinical assessment (e.g. Fugl-Meyer). CONCLUSION: This review
      confirms the potential for robotic therapy to improve UE function in children
      with CP. However, the paucity of group design studies summons the need for more
      rigorous research before conclusive recommendations can be made.

PMID- 24724588
TI  - Blockade of interleukin-8 receptor signalling inhibits cyst development in vitro,
      via suppression of cell proliferation in autosomal polycystic kidney disease.
AB  - AIM: Autosomal dominant polycystic kidney disease (ADPKD) is a highly prevalent
      inherited disorder and results in the progressive development of cysts in both
      kidneys. In recent studies, several cytokines and growth factors secreted by the
      cyst-lining epithelia were identified to be upregulated and promote cyst growth.
      According to our previous study, chemokines with a similar amino acid sequence as
      human interleukin-8 (IL-8) are highly expressed in a rodent model with renal
      cysts. Therefore, in this study, we focused on whether IL-8 signalling is
      associated with renal cyst formation, and tested the possibility of IL-8 as a new
      therapeutic target for ADPKD. METHODS: Expression of IL-8 and its receptor were
      screened either by enzyme linked immunosorbent assay (ELISA) or Western blot.
      Inhibited IL-8 signalling by antagonist for IL-8 receptor or gene silencing was
      tested in molecular levels, mainly through Western blot. And cell proliferation
      was measured by XTT assays. Finally, a three-dimensional culture was performed to
      understand how IL-8 affected cyst formation, in vitro. RESULTS: Interleukin-8
      secretion and expression of its receptor highly increased in two different human
      ADPKD cell lines (WT9-7 and WT9-12), compared to normal human renal cortical
      epithelial cell line. Cell proliferation, which is mediated by IL-8 signal, was
      inhibited either by an antagonist or siRNA targeting for IL-8 receptor. Finally,
      a three-dimensional culture showed an alleviation of cystogenesis in vitro, after
      blocking the IL-8 receptor signals. CONCLUSION: These results suggest that IL-8
      and its signalling molecules could be new biomarkers and a therapeutic target of
      ADPKD.

PMID- 24724589
TI  - Diabetes, sleep and metformin.

PMID- 24724590
TI  - Impact of digestion conditions on phosphoproteomics.
AB  - In the past few years, the focus of phosphoproteomics has shifted from merely
      qualitative to quantitative and targeted studies. Tryptic digestion is a critical
      step that directly affects quantification and that can be impaired by
      phosphorylation. Therefore, we systematically characterized the digestion
      efficiency of 19 nonmodified and phosphorylated model peptides. Whereas we
      quantified a strong reduction of tryptic cleavage within phosphorylated PKA
      motifs (R)-R-X-pS/pT and also R-X-X-pT sequences, (R)-R-X-pY sequences were
      almost unaffected. Structural prediction implied the formation of salt bridges
      between R/K cleavage sites and phosphoamino acids pS/pT as the main reason for
      impaired tryptic digestion. We evaluated different conditions to optimize the
      digestion of such "resistant" phosphopeptides, yielding a substantial improvement
      of digestion efficiency. We performed a quantitative large-scale phosphoproteomic
      analysis of human platelets to validate our findings in a complex biological
      sample. Here, increasing trypsin concentrations up to a trypsin to peptide ratio
      of 1:10 led to a significant gain (i) in the overall number of phosphorylation
      sites (up to 9%) and (ii) in the intensities of individual phosphopeptides,
      thereby improving the sensitivity of phosphopeptide quantification. Still, for
      certain sequences, the negative impact of phosphorylation on digestion efficiency
      will further complicate the analysis of phosphorylation stoichiometry. 

PMID- 24724591
TI  - Ex vivo comparison of the biomechanical properties of hand-sewn and stapled
      jejunoileal anastomoses in horses.
AB  - OBJECTIVE: To compare bursting strength, construction time, and anastomotic
      dimensions of 4 jejunoileal anastomotic techniques. STUDY DESIGN: Experimental ex
      vivo study. ANIMALS: Adult horses (n = 12). METHODS: Jejunoileal anastomoses were
      constructed from harvested ileal and distal jejunal segments using a single-layer
      Lembert technique (1HS), double-layer simple continuous/Cushing technique (2HS),
      stapled side-to-side technique (SS), or stapled functional end-to-end technique
      (FEE). Anastomotic construction time was recorded. Bursting pressures (BP),
      bursting wall tension (BWT), percentage of mean anastomotic luminal diameter
      reduction, percentage of luminal diameter reduction relative to adjacent ileal
      and jejunal diameters and stomal length, were calculated. RESULTS: FEE had the
      shortest construction time. BP of 1HS and 2HS was significantly higher than FEE
      and SS (P < .001), which were not different from each other (P = .67). There were
      no significant differences in BP (P = .25) and BWT (P = .21) between 1HS and 2HS.
      Mean luminal diameter reduction was less for 1HS (25.1%) than for 2HS (34.8%),
      however, not statistically different (P = .12). Luminal diameter reduction
      relative to ileal diameter was significantly less for 1HS (15.2%) than for 2HS
      (28.47%; P = .012). Luminal diameter reduction relative to jejunal diameter was
      less for 1HS (32.4%) than 2HS (44.6%) but not statistically different; P = .07).
      Stomal length was significantly larger for SS (9.93 cm) than FEE (7.32 cm; P =
      .0002). CONCLUSION: 1HS and 2HS jejunoileal anastomosis are equal in strength;
      however, 1HS results in less relative luminal diameter reduction. SS and FEE have
      comparable strength but fail at significantly lower BPs than hand-sewn
      jejunoileal anastomoses.

PMID- 24724596
TI  - Age and etiology of childhood epidermolysis bullosa mortality.
AB  - Epidermolysis bullosa (EB) is a heterogeneous group of congenital blistering
      diseases that are usually present in the neonatal period. They are characterized
      by blister formation in response to rubbing or frictional trauma. EB is
      classified into three major categories, each with many subtypes based on the
      precise location at which separation or blistering occurs, namely epidermolysis
      bullosa simplex (EBS), junctional epidermolysis bullosa (JEB), and dystrophic
      epidermolysis bullosa (DEB). We describe the causes and ages of death of three
      cases of EB in Hong Kong. A 24-year-old male with EBD diagnosed in the neonatal
      period lived a withdrawn life after completing secondary school and died of
      metastaic squamous cell carcinoma. Two neonates of consanguineous Pakistani
      parents, one with JEB and the other with EB-Pyloric Atresia variant, died of
      sepsis in infancy. We performed an extensive literature review of the causes and
      ages of death of these diseases. EB is a heterogeneous inherited blistering skin
      disease associated with significant morbidity and mortality. EBS is occasionally
      associated with death at early ages with sepsis. Patients with JEB usually died
      of sepsis at young age. DEB patients often survive to adulthood and die of
      cardiopulmonary and renal complications. Squamous cell carcinoma and metastases
      are unique in DEB. 

PMID- 24724597
TI  - Situation analysis of the National Comprehensive Cancer Control Program (2013) in
      the I. R. of Iran; assessment and recommendations based on the IAEA imPACT
      mission.
AB  - INTRODUCTION: Iran was engaged in the Program of Action for Cancer Therapy (PACT)
      in 2012, and delegates from the International Atomic Energy Agency (IAEA), and
      the World Health Organization (WHO) evaluated the National Cancer Control Program
      (NCCP) status (the imPACT mission), based on which they provided recommendations
      for improvements of NCCP in the I.R. of Iran. We reported the results of this
      situational analysis and discussed the recommendations and their implication in
      the promotion of NCCP in the I.R. of Iran.  METHODS: International delegates
      visited the I.R. of Iran and evaluated different aspects and capacities of NCCP
      in Iran. In addition, a Farsi version of the WHO/IAEA self-assessment tool was
      completed by local experts and stakeholders, including experts from different
      departments of the Ministry of Health and Medical Education (MOHME) and
      representatives from the National Cancer Research Network (NCRN). Following these
      evaluations, the PACT office provided recommendations for improving the NCCP in
      Iran. Almost all the recommendations were endorsed by MOHME. RESULTS: The PACT
      program provided 31 recommendations for improvement of NCCP in Iran in six
      categories, including planning, cancer registration and information, prevention,
      early detection, diagnosis and treatment, and palliative care. The most important
      recommendation was to establish a strong, multi-sectoral NCCP committee and
      develop an updated national cancer control program. CONCLUSION: The imPACT
      mission report provided a comprehensive view about the NCCP status in Iran. An
      appropriate response to these recommendations and filing the observed gaps will
      improve the NCCP status in the I.R. of Iran.

PMID- 24724595
TI  - Novel aspects of glucocorticoid actions.
AB  - Normal hypothalamic-pituitary-adrenal (HPA) axis activity leading to the rhythmic
      and episodic release of adrenal glucocorticoids (GCs) is essential for body
      homeostasis and survival during stress. Acting through specific intracellular
      receptors in the brain and periphery, GCs regulate behaviour, as well as
      metabolic, cardiovascular, immune and neuroendocrine activities. By contrast to
      chronic elevated levels, circadian and acute stress-induced increases in GCs are
      necessary for hippocampal neuronal survival and memory acquisition and
      consolidation, as a result of the inhibition of apoptosis, the facilitation of
      glutamatergic neurotransmission and the formation of excitatory synapses, and the
      induction of immediate early genes and dendritic spine formation. In addition to
      metabolic actions leading to increased energy availability, GCs have profound
      effects on feeding behaviour, mainly via the modulation of orexigenic and
      anorixegenic neuropeptides. Evidence is also emerging that, in addition to the
      recognised immune suppressive actions of GCs by counteracting adrenergic pro
      inflammatory actions, circadian elevations have priming effects in the immune
      system, potentiating acute defensive responses. In addition, negative-feedback by
      GCs involves multiple mechanisms leading to limited HPA axis activation and
      prevention of the deleterious effects of excessive GC production. Adequate GC
      secretion to meet body demands is tightly regulated by a complex neural circuitry
      controlling hypothalamic corticotrophin-releasing hormone (CRH) and vasopressin
      secretion, which are the main regulators of pituitary adrenocorticotrophic
      hormone (ACTH). Rapid feedback mechanisms, likely involving nongenomic actions of
      GCs, mediate the immediate inhibition of hypothalamic CRH and ACTH secretion,
      whereas intermediate and delayed mechanisms mediated by genomic actions involve
      the modulation of limbic circuitry and peripheral metabolic messengers.
      Consistent with their key adaptive roles, HPA axis components are evolutionarily
      conserved, being present in the earliest vertebrates. An understanding of these
      basic mechanisms may lead to novel approaches for the development of diagnostic
      and therapeutic tools for disorders related to stress and alterations of GC
      secretion. 

PMID- 24724598
TI  - Attitude of cancer patients toward diagnosis disclosure and their preference for
      clinical decision-making: a national survey.
AB  - OBJECTIVES: There is still contradictory evidence on disclosure preferences
      regarding cancer diagnosis. The aim of this study was to evaluate the preference
      of cancer patients for knowing the truth about their disease, as well as the
      factors that might have an impact on these preferences. METHOD: This study was
      conducted in 11 cancer centers in Iran. A questionnaire was used to collect data,
      and all patients above 15 years of age who were willing to participate were
      included in the study. The patients were asked if they were aware of the
      malignant nature of their disease, and if they came to know about their disease
      at the time of initial diagnosis, or later. The patients were then asked about
      the way they looked upon their disease. In the final part of the questionnaire,
      the participants were asked the level of involvement they prefer to have in
      making treatment decisions. RESULTS: In total, 1226 patients were enrolled in
      this study, only 565 (46.7%) of whom were aware of their disease at the time of
      diagnosis, and 878 (72.7%) at the time of interview, while 980 (85.2%) were
      willing to receive information about their disease. Patients' awareness was
      significantly associated with age under 50 years, female gender, having breast,
      skin or head and neck cancer, and having medical care in Shiraz or Hamadan while
      it was not associated with the stage or accompanying illness. CONCLUSION: While
      the majority of Iranian cancer patients prefer to be aware of the nature of their
      disease and have an active role in treatment decision making, they do not receive
      this information.

PMID- 24724599
TI  - Cost-effectiveness of mammography screening for breast cancer in a low
      socioeconomic group of Iranian women.
AB  - BACKGROUND: Breast cancer is the most common cancer among women. Mammography
      screening has been used in many countries to reduce early deaths caused by breast
      cancer. It is important to ensure that screening programs are effective and
      efficient. We conducted a study to assess the cost-effectiveness of a national
      breast cancer screening program implemented in Iran. METHODS: The perspective of
      the present study was the health system. Over 26,000 women aged 35 and higher, of
      low socioeconomic background were recruited from ten cities in the program. We
      used case-finding as the outcome indicator for assessing effectiveness of the
      program. We measured the service provision costs, the coordination costs and
      supervision costs of the program that included the staff costs, and measured cost
      per detected case. We also conducted sensitivity analyses and calculated false
      positive rates as a result of the screening program. RESULTS: The total cost of
      breast cancer screening program was estimated at $377,797. The program resulted
      in the identification of 24 patients with breast cancers, not different from
      baseline expectations without a screening program. The cost per cancer detected
      was calculated $15,742. The minimum and maximum cost per breast cancer detected
      were about $13,524 and $16,947, respectively. We observed a false-positive rate
      of 7.5% among the target population. CONCLUSION: Our findings suggest that the
      mammography screening program was not cost-effective. Although there were
      technical efficiency issues in the conduct of the program, the findings do not
      support the implementation of national mammography screening programs in Iran in
      women aged less than 50 years. Careful studies of such programs for higher age
      groups are also recommended before they are rolled-out nationally.

PMID- 24724601
TI  - Factors affecting professional delay in diagnosis and treatment of oral cancer in
      Iran.
AB  - BACKGROUND: Oral cancer is the most common malignant tumor among head and neck
      cancers. Delay in diagnosis affects the treatment and prognosis of oral cancer.
      We measured the professional delay in the diagnosis and its attributes in the
      Cancer Institute of Iran, the largest referral center for oral cancer patients in
      the country.  METHODS: We interviewed oral cancer patients to measure the delay
      and used case-control approach to study association of various prognostic factors
      with professional delay and tumor stage. RESULT: Out of 206 patients, 71.4% were
      diagnosed at the advanced stage. The median of the patient, professional and
      total delays were 45, 86 and 140 day, receptively. In the univariate model,
      prescription of medicines like analgesics (OR = 5.3, 95% CI 2.2-12.9) and history
      of dental procedure (OR=6.8, 95% CI 1.7-26.9) were associated with higher risk of
      delay compared to patient who were biopsied from the beginning. History of loose
      teeth increased risk of delay 4 times (OR = 4.0, 95% CI 1.6-9.8). Patients with
      primary education had 70% lower risk of delay compared to the illiterate patients
      (OR = 0.3, 95% CI 0.1-0.7) and the risk was lower among patients who had diploma
      (OR = 0.04, 95% CI 0-0.7) and college education (OR = 0.1, 95% CI 0-0.4). The
      delayed patients were diagnosed in more advanced stage compared to the patients
      without delay (OR = 2.1, 95% CI 1.0-4.4). CONCLUSION: Development of a national
      guideline for follow-up of oral lesions, training and awareness of health care
      professionals about oral cancer diagnosis may decrease the delay and improve the
      oral cancer outcome in Iran.

PMID- 24724600
TI  - Endoscopic screening for precancerous lesions of the esophagus in a high risk
      area in Northern Iran.
AB  - BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is a major health problem
      in many developing countries including Iran. ESCC has a very poor prognosis,
      largely due to late diagnosis. As a first step in developing an early detection
      and treatment program, we conducted a population-based endoscopic screening for
      ESCC and its precursor lesion, esophageal squamous dysplasia (ESD) in
      asymptomatic adults from Golestan Province, northern Iran, a high-risk area for
      ESCC, to evaluate the feasibility of such a program and to document the
      prevalence and risk factor correlates of ESD. METHODS: This cross-sectional study
      was conducted among participants of the Golestan Cohort Study (GCS), a population
      based cohort of 50,000 adults in eastern Golestan Province. Randomly selected GCS
      participants were invited by telephone. Those who accepted were referred to a
      central endoscopy clinic. Eligible subjects were consented and then asked to fill
      in a brief questionnaire. Detailed information about selected risk factors was
      obtained from the GCS main database. Endoscopic examination with Lugol's iodine
      staining was performed, biopsies were taken from unstained lesions as well as the
      normally stained mucosa of the esophagus, and the biopsies were diagnosed by
      expert pathologists according to previously described criteria. RESULTS: In
      total, 1906 GCS subjects were invited, of whom only 302 subjects (15.8%) were
      successfully enrolled. Esophagitis (29.5%) and ESD (6.0%) were the most common
      pathological diagnoses. Turkmen ethnicity (adjusted OR = 8.61; 95%CI: 2.48
      29.83), being older than the median age (OR = 7.7; 95% CI: 1.99-29.87), and using
      deep frying cooking methods (OR = 4.65; 95%CI: 1.19-18.22) were the strongest
      predictors for ESD. There were significant relationships between esophagitis and
      smoking (p-value<0.001), drinking hot tea (P value = 0.02) and lack of education
      (P value = 0.004). CONCLUSION: We observed a low rate for participation in
      endoscopic screening. Overall prevalence of ESD was 6.0%. Developing non
      endoscopic primary screening methods and screening individuals with one or more
      risk factors may improve these rates.

PMID- 24724602
TI  - Detection and biological characteristic of FLT3 gene mutations in children with
      acute leukemia.
AB  - INTRODUCTION: FLT3 ITD and D835 mutations occur in high frequency in AML and to a
      lower rate in ALL patients with poor prognosis. METHODS: ITD and D835 mutations
      were studied in 100 diagnosed acute leukemia patients including 27 AML and 73 ALL
      with various FAB classifications by PCR and PCR-RFLP, respectively. Subsequently,
      PCR products of positive samples were confirmed by sequencing analyses. RESULTS:
      ITD mutations occurred in 10% of all pediatric acute leukemia, including AML and
      ALL. 25.9% of AML patients harbor a mutation in the ITD in various subtypes. The
      frequency of ITD mutations was 4% in ALL. Various insertions of nucleotides in
      ITD were observed, similar to those described in the literature previously.
      CONCLUSION: These preliminary data suggest that flt3-ITD mutations may play an
      important role in leukemogenesis in a proportion of children, particularly in the
      case of AML.

PMID- 24724603
TI  - Meningioma protein-protein interaction network.
AB  - BACKGROUND: Meningioma is one of the most common central nervous system tumors
      that derived from meningothelial (arachnoid cap) cells. This paper identified the
      network-based Protein-Protein Interactions (PPI) for meningioma relative to
      healthy control. METHODS: Gene expression data including 384 gene or protein
      names extracted from a number of beforehand investigations. RESULTS: Out of these
      384 proteins, 176 were found to be exclusively expressed in meningiomas and 208
      proteins were down-regulated. The networks of related differentially expressed
      genes were explored using cytoscape and the PPI analysis methods such as MCODE
      and ClueGO. Results analysis introduced a number of hub proteins and 27 clusters
      (protein complex) with distinctive seed genes. Identified ClueGO Pathways based
      on subnetworks mined by MCODE composed of positive regulation in RBC homeostasis,
      dysregulation of transport from ER to Golgi, disruption regulation of cell cycle
      and antigen processing and presentation of exogenous peptide antigen and
      neutralization of exogenous dsRNA. Combination of over expression of TCEA1,
      UBE2E1, XRCC5, IFIT1, IFIT-3, MCM2, and MCM7 and under expression of CDC25A,
      SEC31A, and CDK6 can serve as diagnostic biomarker panel for meningiomas.
      CONCLUSION: These introduced network-based biomarkers for the meningioma patterns
      may be helpful in diagnosis, prognosis and treatment processes however biomarker
      validation is necessary.

PMID- 24724604
TI  - HeLa cell line xenograft tumor as a suitable cervical cancer model: growth
      kinetic characterization and immunohistochemistry array.
AB  - BACKGROUND: Cervical cancer is the seventh most common malignancy in both genders
      combined and the third most common cancer in women. Despite significant progress
      in treatments, cervical cancer is not completely curable. Therefore, further
      research is necessary in this area. Animal models are one of the most practical
      tools in the field of cancer research. The present study aimed to characterize
      the growth behavior and surface markers of HeLa cells after heterotopic and
      systemic inoculation to athymic nude mice. METHODS: Ten 6-week old female athymic
      C57BL/6 nude mice were used in this study. HeLa cells were inoculated into the
      flank or tail vein. The tumor volume was calculated and growth curves were drawn.
      Tumor-bearing mice were sacrificed and the lesions obtained after harvesting were
      analyzed in a pathology lab. Subsequently, one slide per tumor was stained with
      hematoxylin and eosin (H&E) and other slides were stained immunohistochemically
      by cytokeratins (CK), vimentin, P53, CD34, and Ki-67. RESULTS: Tumor take rate,
      mean doubling time and latency period were 94.4%, 5.29 +/- 3.57 days and 15.27
      days, respectively. H&E results revealed highly malignant hyperchromatin
      epithelial cells. Immunohistochemical examination of the heterotopic tumors
      indicated greater expression of CK and less expression of vimentin compared to
      the metastatic ones. Sixty percent of cells were P53-positive and more than 80%
      were Ki-67-positive. CD34 expression indicated the intensity of angiogenesis in
      tumor. CONCLUSION: This study represents a comprehensive description of a HeLa
      xenograft model for in vivo investigations, enabling researchers to assess new
      treatments for cervical cancer.

PMID- 24724605
TI  - Ferulago angulata flower and leaf extracts inhibit angiogenesis in vitro through
      reducing VEGF-A and VEGFR-2 genes expression.
AB  - BACKGROUND: Ferulago angulata (Apiacea) has been used in Iranian traditional
      medicine since ancient times and its various health care and pharmacological
      benefits have been demonstrated recently. In this study, for the first time, we
      have investigated the effects of F. angulata flower and leaf ethanol extracts on
      angiogenesis, as the key process in tumor growth, invasion and metastasis.
      METHODS: Cytotoxic effects of different concentrations (20-140 ug/mL) of each
      extract were assessed on human umbilical vein endothelial cells (HUVECs) using
      neutral red uptake assay. After evaluating the less toxic concentrations (up to
      80 ug/mL), we performed three-dimensional angiogenesis, tube formation and
      migration assays to assess the key properties of HUVECs, including the
      angiogenesis process, in response to the extracts. Finally, quantitative gene
      expression analysis of VEGF-A and VEGFR-2, two critical mediators of
      angiogenesis, was performed using real-time RT-PCR. RESULTS: Both flower and leaf
      extracts exhibited concentration-dependent inhibition of sprouting, tube
      formation and migration capacities of HUVECs. For the flower extract, the
      respective IC50 values were 25.79, 26.52 and 38.92 ug/mL while for the leaf
      extract, the corresponding IC50 values were 34.18, 41.24 and 28.69 ug/mL. Both
      flower and leaf extracts downregulated VEGF-A and VEGFR-2 genes relative to the
      GAPDH gene as the internal control at concentrations of 60 and 80 ug/mL,
      respectively. CONCLUSION: These findings suggest that both flower and leaf
      extracts may contain anti-angiogenic compounds and may have the capacity to be
      utilized in tumor anti-angiogenic therapy strategies.

PMID- 24724606
TI  - Cancers of the upper gastro-intestinal tract: a review of somatic mutation
      distributions.
AB  - Cancers of the upper gastro-intestinal tract (UGIT) comprise esophageal, esophago
      gastric junction, stomach and duodenal cancers. Together, these cancers represent
      over 1.5 million cases and are the cause of about 1.25 million deaths annually.
      This group of cancers encompasses diseases with marked disparities in etiology,
      geographic distribution, histopathological features and frequency. Based on
      histological origin, squamous cell carcinoma of the esophagus (ESCC), which
      arises through a dysplasia-carcinoma sequence within the squamous mucosa, is a
      completely different cancer than junction, stomach and duodenal cancers, which
      develop within glandular epithelia through cascades involving inflammation,
      metaplasia, dysplasia and carcinoma. At the frontline between these two
      histological domains, cancers of the esophago-gastric junction constitute a mixed
      group of glandular tumors including distal esophageal adenocarcinomas and cancers
      arising within the most proximal part of the stomach - the cardia. Most of UGIT
      cancers are sporadic, although familial susceptibility genes have been identified
      for stomach and rare cases of ESCC. We have used the COSMIC database
      (http://www.sanger.ac.uk/genetics/CGP/cosmic/) to identify genes commonly mutated
      in UGIT cancers. Regardless of etiology and histopathology, three genes are
      mutated in at least 5% of UGIT cancers: TP53, CDKN2a and PIK3CA. Another three
      genes, NFE2L2, PTCH1 and NOTCH1, are mutated in ESCC only. Conversely, genes of
      the RAS family and of the CDH1/APC/CTNNB1 pathway are mutated only in non
      squamous cancers, with differences in mutated genes according to topography. We
      review the potential functional significance of these observations for
      understanding mechanisms of UGIT carcinogenesis. 

PMID- 24724607
TI  - Intramedullary spinal cord metastasis from endometrioid adenocarcinoma.
AB  - Intramedullary spinal cord metastases are rare .The majority of these metastases
      reportedly spread from lung cancer in the cervical region; however, they have
      been seen to arise from a variety of other primary sources. Here, we report what
      is, to the best of our knowledge, the first known case of an intramedullary
      spinal cord metastatic lesion in the conus region arising from primary
      endometrioid adenocarcinoma. 

PMID- 24724608
TI  - Photoclinic.

PMID- 24724609
TI  - Abul- Hasan al-Tabari: a review of his views and works.
AB  - Abul-Hasan al-Tabari was a 10th century Persian physician born in Tabaristan. He
      was a creative and innovative physician who avoided emulating treatments without
      investigating and examining them. Tabari was an encyclopedist and had a holistic
      view to medicine. Investigation of the views of this great Persian scholar
      indicated that his scientific and moral characteristics contain: paying adequate
      attention to philosophy and medical ethics, citing other scholars' works,
      attention to the necessity of clinical and hospital training, emphasizing
      indigenous therapy and scientific and responsible treatment with medical faults
      and discovery of Sarcoptes scabiei. Tabari has written valuable articles on
      different medical sciences; however, he is especially famous for authoring the al
      Mu'alajat al-Buqratiya (Hippocratic Treatments) - an important medical
      encyclopedia. Several of Al-Tabari's succeeding scholars and physician have
      referred to the al-Mu'alajat al-Buqratiya in their medical articles. The aim of
      this study is further introduction of this great physician and assessment of his
      theories and key works. 

PMID- 24724610
TI  - DSE-FRET: A new anticancer drug screening assay for DNA binding proteins.
AB  - Nuclear factor-kappaB (NF-kappaB) is a key regulator of cancer progression and
      the inflammatory effects of disease. To identify inhibitors of DNA binding to NF
      kappaB, we developed a new homogeneous method for detection of sequence-specific
      DNA-binding proteins. This method, which we refer to as DSE-FRET, is based on two
      phenomena: protein-dependent blocking of spontaneous DNA strand exchange (DSE)
      between partially double-stranded DNA probes, and fluorescence resonance energy
      transfer (FRET). If a probe labeled with a fluorophore and quencher is mixed with
      a non-labeled probe in the absence of a target protein, strand exchange occurs
      between the probes and results in fluorescence elevation. In contrast, blocking
      of strand exchange by a target protein results in lower fluorescence intensity.
      Recombinant human NF-kappaB (p50) suppressed the fluorescence elevation of a
      specific probe in a concentration-dependent manner, but had no effect on a non
      specific probe. Competitors bearing a NF-kappaB binding site restored
      fluorescence, and the degree of restoration was inversely correlated with the
      number of nucleotide substitutions within the NF-kappaB binding site of the
      competitor. Evaluation of two NF-kappaB inhibitors, Evans Blue and
      dehydroxymethylepoxyquinomicin ([-]-DHMEQ), was carried out using p50 and p52
      (another form of NF-kappaB), and IC50 values were obtained. The DSE-FRET
      technique also detected the differential effect of (-)-DHMEQ on p50 and p52
      inhibition. These data indicate that DSE-FRET can be used for high throughput
      screening of anticancer drugs targeted to DNA-binding proteins. 

PMID- 24724611
TI  - Transurethral resection of the prostate after radiotherapy for prostate cancer:
      impact on quality of life.
AB  - OBJECTIVES: To evaluate the impact of transurethral resection of the prostate on
      quality of life after radiotherapy for prostate cancer. METHODS: A group of 49
      consecutive patients with and 487 without prior transurethral resection of the
      prostate responded to the Expanded Prostate Cancer Index Composite questionnaire
      before, on the last day, and a median time of 2 months and 16 months after
      external beam radiotherapy (70-78 Gy). A matched-pair analysis was used to avoid
      the influence of treatment-associated confounding factors, including dose,
      treatment volume and hormonal therapy. RESULTS: Significantly smaller acute
      urinary score changes relative to baseline levels resulted with versus without
      prior transurethral resection of the prostate (mean function/bother score
      decrease of 3/6 vs 18/21 points at the end of radiotherapy; P < 0.01), affecting
      urinary incontinence (pads to control urinary leakage in 4% vs 24%; P = 0.03) and
      irritative/obstructive symptoms (big/moderate problem with weak urinary stream in
      11% vs 37%; P = 0.02). As opposed to acute changes, transurethral resection of
      the prostate was a significant predisposing factor for a long-term urinary
      function score decrease >10 points (20% vs 6% of patients with vs without prior
      resection; P = 0.04). Urinary incontinence risk was higher for patients with a
      longer time from resection to radiotherapy. CONCLUSIONS: Transurethral resection
      of the prostate significantly affects acute (considerably fewer symptoms) and
      long-term (relevant toxicity in some cases) urinary quality of life after
      radiotherapy for prostate cancer.

PMID- 24724612
TI  - Female and male genetic effects on offspring paternity: additive genetic
      (co)variances in female extra-pair reproduction and male paternity success in
      song sparrows (Melospiza melodia).
AB  - Ongoing evolution of polyandry, and consequent extra-pair reproduction in
      socially monogamous systems, is hypothesized to be facilitated by indirect
      selection stemming from cross-sex genetic covariances with components of male
      fitness. Specifically, polyandry is hypothesized to create positive genetic
      covariance with male paternity success due to inevitable assortative
      reproduction, driving ongoing coevolution. However, it remains unclear whether
      such covariances could or do emerge within complex polyandrous systems. First, we
      illustrate that genetic covariances between female extra-pair reproduction and
      male within-pair paternity success might be constrained in socially monogamous
      systems where female and male additive genetic effects can have opposing impacts
      on the paternity of jointly reared offspring. Second, we demonstrate nonzero
      additive genetic variance in female liability for extra-pair reproduction and
      male liability for within-pair paternity success, modeled as direct and
      associative genetic effects on offspring paternity, respectively, in free-living
      song sparrows (Melospiza melodia). The posterior mean additive genetic covariance
      between these liabilities was slightly positive, but the credible interval was
      wide and overlapped zero. Therefore, although substantial total additive genetic
      variance exists, the hypothesis that ongoing evolution of female extra-pair
      reproduction is facilitated by genetic covariance with male within-pair paternity
      success cannot yet be definitively supported or rejected either conceptually or
      empirically. 

PMID- 24724613
TI  - Interleukin-18 as a target for modulation of irinotecan-induced intestinal
      toxicity: a step towards a better therapeutic index?: Commentary on Lima-Junior
      et al., Br J Pharmacol 171: 2335-2350.

PMID- 24724614
TI  - Coherent exciton dynamics in supramolecular light-harvesting nanotubes revealed
      by ultrafast quantum process tomography.
AB  - Long-lived exciton coherences have been recently observed in photosynthetic
      complexes via ultrafast spectroscopy, opening exciting possibilities for the
      study and design of coherent exciton transport. Yet, ambiguity in the
      spectroscopic signals has led to arguments against interpreting them in terms of
      exciton dynamics, demanding more stringent tests. We propose a novel strategy,
      quantum process tomography (QPT), for ultrafast spectroscopy and apply it to
      reconstruct the evolving quantum state of excitons in double-walled
      supramolecular light-harvesting nanotubes at room temperature from eight
      narrowband transient grating experiments. Our analysis reveals the absence of
      nonsecular processes, unidirectional energy transfer from the outer to the inner
      wall exciton states, and coherence between those states lasting about 150 fs,
      indicating weak electronic coupling between the walls. Our work constitutes the
      first experimental QPT in a "warm" and complex system and provides an elegant
      scheme to maximize information from ultrafast spectroscopy experiments. 

PMID- 24724615
TI  - Speaking rate effects on articulatory pattern consistency in talkers with mild
      ALS.
AB  - This study investigated speaking rate effects on articulatory pattern consistency
      in talkers with mild amyotrophic lateral sclerosis (ALS) to better understand
      speech rate declines during the early stages of speech deterioration. Eight
      talkers with mild ALS and 11 controls repeated a sentence at their typical rate,
      an accelerated rate, and a reduced rate. Lip and jaw movements were captured
      using a 3-D motion capture system. Results showed that talkers with ALS produced
      more consistent articulatory patterns during typical speech than did controls.
      Further, rate reduction resulted in diminished pattern consistency in both
      groups. Fast speech also elicited less consistent articulatory patterns in
      talkers with ALS. Controls, by contrast, tended to produce more consistent
      patterns during fast speech. Relatively inconsistent patterns during fast speech
      suggest that ALS may negatively affect articulatory control when the speech motor
      system operates near its performance limit. Relatively consistent patterns during
      typical speech indicate a successful adaption to disease-related articulatory
      deficits. Rate reduction does not appear to benefit articulatory stability during
      early stages of speech decline.

PMID- 24724616
TI  - Sex-specific effects of naturally occurring variants in the dopamine receptor D2
      locus on insulin secretion and type 2 diabetes susceptibility.
AB  - AIMS: Modulation of dopamine receptor D2 (DRD2) activity affects insulin
      secretion in both rodents and isolated pancreatic beta-cells. We hypothesized
      that single nucleotide polymorphisms in the DRD2/ANKK1 locus may affect
      susceptibility to type 2 diabetes in humans. METHODS: Four potentially functional
      variants in the coding region of the DRD2/ANKK1 locus (rs1079597, rs6275, rs6277,
      rs1800497) were genotyped and analysed for type 2 diabetes susceptibility in up
      to 25 000 people (8148 with type 2 diabetes and 17687 control subjects) from two
      large independent Dutch cohorts and one Danish cohort. In addition, 340 Dutch
      subjects underwent a 2-h hyperglycaemic clamp to investigate insulin secretion.
      Since sexual dimorphic associations related to DRD2 polymorphisms have been
      previously reported, we also performed a gender-stratified analysis. RESULTS:
      rs1800497 at the DRD2/ANKK1 locus was associated with a significantly increased
      risk for type 2 diabetes in women (odds ratio 1.14 (1.06-1.23); P = 4.1*104) but
      not in men (odds ratio 1.00 (95% CI 0.93-1.07); P = 0.92) or the combined group.
      Although rs1800497 was not associated with insulin secretion, we did find another
      single nucleotide polymorphism in this locus, rs6275, to be associated with
      increased first-phase glucose-stimulated insulin secretion in women (P = 5.5*104)
      but again not in men (P = 0.34). CONCLUSION: The present data identify DRD2/ANKK1
      as a potential sex-specific type 2 diabetes susceptibility gene.

PMID- 24724618
TI  - Effect of dorsal acetabular rim loss on stability of the zurich cementless total
      hip acetabular cup in dogs.
AB  - OBJECTIVE: To evaluate magnitude and mode of acute load to failure of the Zurich
      Cementless acetabular cup prosthesis in cadaveric specimens with and without 50%
      dorsal acetabular rim loss. STUDY DESIGN: In vitro mechanical study. SAMPLE
      POPULATION: Cadaveric hemipelves of adult dogs (n = 8). METHODS: Each pair of
      hemipelves was prepared by dissection of surrounding musculature and implantation
      of a Zurich Cementless acetabular cup prosthesis. One hemipelvis had the dorsal
      rim left intact (group 1) and the contralateral hemipelvis had 50% of the dorsal
      rim excised (group 2). Each hemipelvis underwent acute load to failure with an
      axial load applied through a prosthetic femoral head. Load at failure was
      compared between hemipelves with and without dorsal rim loss with a paired t
      test; P < .05 was considered significant. RESULTS: Mean failure load was not
      significantly different between group 1 (3,713 +/- 362 N) and group 2 (3,640 +/-
      751 N; P = .8). Bone fracture (n = 6), ventroversion of the cup (1), and absolute
      failure unreached at 6,000 N (1) occurred in group 1 and bone fracture (6),
      ventroversion of cup (1), and cup loosening (1) occurred in group 2. CONCLUSIONS:
      Zurich Cementless acetabular cup stability does not appear to be compromised by
      50% acetabular rim loss at normal physiologic weight bearing loads. Thus, for
      this system, modifying procedures such as augmentation of the dorsal acetabular
      rim or deeper reaming for acetabular bed preparation may not be necessary with up
      to 50% dorsal rim loss with the Zurich Cementless acetabular cup.

PMID- 24724617
TI  - Stock-outs of essential health products in Mozambique - longitudinal analyses
      from 2011 to 2013.
AB  - OBJECTIVES: To assess the relationship between health system factors and facility
      level EHP stock-outs in Mozambique. METHODS: Service provisions were assessed in
      26 health facilities and 13 district warehouses in Sofala Province, Mozambique,
      from July to August in 2011-2013. Generalised estimating equations were used to
      model factors associated with facility-level availability of essential drugs,
      supplies and equipment. RESULTS: Stock-out rates for drugs ranged from 1.3% for
      oral rehydration solution to 20.5% for Depo-Provera and condoms, with a mean
      stock-out rate of 9.1%; mean stock-out rates were 15.4% for supplies and 4.1% for
      equipment. Stock-outs at the district level accounted for 27.1% (29/107) of
      facility-level drug stock-outs and 44.0% (37/84) of supply stock-outs. Each 10-km
      increase in the distance from district distribution warehouses was associated
      with a 31% (CI: 22-42%), 28% (CI: 17-40%) or 27% (CI: 7-50%) increase in rates of
      drug, supply or equipment stock-outs, respectively. The number of heath facility
      staff was consistently negatively associated with the occurrence of stock-outs.
      CONCLUSIONS: Facility-level stock-outs of EHPs in Mozambique are common and
      appear to disproportionately affect those living far from district capitals and
      near facilities with few health staff. The majority of facility-level EHP stock
      outs in Mozambique occur when stock exists at the district distribution centre.
      Innovative methods are urgently needed to improve EHP supply chains, requesting
      and ordering of drugs, facility and district communication, and forecasting of
      future EHP needs in Mozambique. Increased investments in public-sector human
      resources for health could potentially decrease the occurrence of EHP stock-outs.

PMID- 24724619
TI  - Sense and avoid requirements for unmanned aircraft systems using a target level
      of safety approach.
AB  - One of the most critical challenges to full integration of unmanned aircraft
      systems (UAS) into the National Airspace System (NAS) is the requirement to
      comply with CFR 14 Part 91.113 to "see and avoid" other aircraft. Various
      attempts have been made to develop systems to "sense and avoid" other aircraft so
      UAS can comply with the intent of the regulation. This article proposes a
      framework to develop effectiveness requirements for any SAA system by linking UAS
      characteristics and operating environments to midair collision risk quantified by
      a fatality rate. The framework consists of a target level of safety (TLS)
      approach using an event tree format. Safety has been identified as the most
      important consideration in the UAS integration process. While safety can be
      defined in many ways, the authors propose using a fatality rate metric that
      follows other statistics used in the industry. This metric allows for the use of
      a TLS approach to the development of SAA requirements for system certification.
      Failure to adequately link system requirements to safety could result in the
      implementation of SAA systems that either do not adequately mitigate the risk
      associated with UAS operations or are overdesigned, resulting in increased cost
      and complexity. This article demonstrates the use of the proposed framework to
      develop specific SAA effectiveness standards based on UAS weight and airspace
      class combinations. 

PMID- 24724620
TI  - Interleukin-4 enhances PARP-dependent DNA repair activity in vitro.
AB  - Eukaryotic cells possess several DNA repair mechanisms, including homologous
      recombination and the non-homologous end-joining (NHEJ) system. There are two
      known NHEJ systems. The major mechanism depends on the catalytic unit of DNA
      dependent protein kinase (DNA-PKcs) and DNA ligase IV, and an alternative
      mechanism (B-NHEJ) depends on poly(ADP-ribose) polymerase (PARP). These systems
      are upregulated by genotoxic agents. Interleukin 4 (IL-4) is an immunoregulatory
      cytokine that is secreted by immune cells upon contact with certain genotoxic
      compounds and is known to regulate several genes encoding components of DNA
      repair systems in human monocytes. We have investigated the possible effects of
      IL-4 on the DNA repair process within murine and human cells exposed to selected
      genotoxic compounds. In a series of experiments, including the comet assay, cell
      surface annexin V staining, analysis of histone H2AX phosphorylation, and a DNA
      end-joining assay, we observed that IL-4 decreased DNA damage in murine
      fibroblasts and human glioblastoma cells exposed to genotoxic agents and
      increased DNA ligation activity in the nuclei of these cells in a process that
      depended on PARP. These observations suggest that IL-4 is capable of upregulating
      the alternative NHEJ DNA repair mechanism in murine and human cells. 

PMID- 24724621
TI  - Murine solid tumours as a novel model to study bacterial biofilm formation in
      vivo.
AB  - Bacteria of many species are able to invade and colonize solid tumours in mice.
      We have focused on Salmonella enterica serovar Typhimurium. Detailed analysis
      revealed that such tumour-invading Salmonella form biofilms, thus providing a
      versatile in vivo test system for studying bacterial phenotypes and host-pathogen
      interactions. It appears that biofilm formation by S. typhimurium is induced as a
      defence against the immune system of the host, and in particular against
      neutrophils. Further, we extended our work to the clinically more relevant
      biofilm infection by Pseudomonas aeruginosa. The induction of P. aeruginosa
      biofilms in neoplastic tissue appears to be elicited as a reaction against the
      immune system. Reconstitution experiments reveal that T cells are responsible for
      biofilm induction. Isogenic mutants that are no longer able to form biofilms can
      be used for comparison studies to determine antimicrobial resistance, especially
      therapeutic efficacy against P. aeruginosa located in biofilms. 

PMID- 24724622
TI  - Editorial comment to Multidisciplinary clinical strategies for encapsulating
      peritoneal sclerosis in peritoneal dialysis: update from Japan.

PMID- 24724623
TI  - Engaging nurses to strengthen medication safety: Fostering and capturing change
      with restorative photographic research methods.
AB  - We used participatory photographic research methods adapted from the field of
      ecological restoration to engage Brazilian intensive care unit nurses in a
      critical review of medication safety in their work environment. Using focus
      groups, practitioner-led photo walkabouts with photo narration, and photo
      elicitation focus groups in iterative phases of data collection and analysis,
      nurses developed and implemented several practical and cultural improvements for
      their unit. Participants focussed on organizing the medication room for efficient
      workflow and accessible supplies, improving reporting practices, and
      reconsidering how they could manage safety issues in their unit and in the
      hospital as a whole. Our results demonstrated that restorative photographic
      research methods enabled participants to (re)think and redesign their work
      environment in keeping with several recommended practices for improving
      medication management. It also validated the need for continuous evidence
      informed improvements if nurses hope to optimize medication safety in the complex
      systems of intensive care. 

PMID- 24724624
TI  - PKC-NF-kappaB are involved in CCL2-induced Nav1.8 expression and channel function
      in dorsal root ganglion neurons.
AB  - CCL2 [chemokine (C-C motif) ligand 2] contributes to the inflammation-induced
      neuropathic pain through activating VGSC (voltage-gated sodium channel)-mediated
      nerve impulse conduction, but the underlying mechanism is currently unknown. Our
      study aimed to investigate whether PKC (protein kinase C)-NF-kappaB (nuclear
      factor kappaB) is involved in CCL2-induced regulation of voltage-gated sodium
      Nav1.8 currents and expression. DRG (dorsal root ganglion) neurons were prepared
      from adult male Sprague-Dawley rats and incubated with various concentration of
      CCL2 for 24 h. Whole-cell patch-clamps were performed to record the Nav1.8
      currents in response to the induction by CCL2. After being pretreated with 5
      and10 nM CCL2 for 16 h, CCR2 [chemokine (C-C motif) receptor 2] and Nav1.8
      expression significantly increased and the peak currents of Nav1.8 elevated from
      the baseline 46.53+/-4.53 pA/pF to 64.28+/-3.12 pA/pF following 10 nM CCL2
      (P<0.05). Compared with the control, significant change in Nav1.8 current density
      was observed when the CCR2 inhibitor INCB3344 (10 nM) was applied. Furthermore,
      inhibition of PKC by AEB071 significantly eliminated CCL2-induced elevated Nav1.8
      currents. In vitro PKC kinase assays and autoradiograms suggested that Nav1.8
      within DRG neurons was a substrate of PKC and direct phosphorylation of the
      Nav1.8 channel by PKC regulates its function in these neurons. Moreover, p65
      expression was significantly higher in CCL2-induced neurons (P<0.05), and was
      reversed by treatment with INCB3344 and AEB071. PKC-NF-kappaB are involved in
      CCL2-induced elevation of Nav1.8 current density by promoting the phosphorylation
      of Nav1.8 and its expression.

PMID- 24724626
TI  - The enigma of 36 completed weeks of gestation: 36 0/7 or 36 6/7?

PMID- 24724625
TI  - High-density epicardial activation mapping to optimize the site for video
      thoracoscopic left ventricular lead implant.
AB  - BACKGROUND: The left ventricular (LV) lead local electrogram (EGM) delay from the
      beginning of the QRS complex (QLV) is considered a strong predictor of response
      to cardiac resynchronization therapy. We have developed a method for fast
      epicardial QLV mapping during video-thoracoscopic surgery to guide LV lead
      placement. METHODS: A three-port, video-thoracoscopic approach was used for LV
      free wall epicardial mapping and lead implantation. A decapolar
      electrophysiological catheter was introduced through one port and systematically
      attached to multiple accessible LV sites. The pacing lead was targeted to the
      site with maximum QLV. The LV free wall activation pattern was analyzed in 16 pre
      specified anatomical segments. RESULTS: We implanted LV leads in 13 patients with
      LBBB or IVCD. The procedural and mapping times were 142 +/- 39 minutes and 20 +/-
      9 minutes, respectively. A total of 15.0 +/- 2.2 LV segments were mappable with
      variable spatial distribution of QLV-optimum. The QLV ratio (QLV/QRSd) at the
      optimum segment was significantly higher (by 0.17 +/- 0.08, p < 0.00001) as
      compared to an empirical midventricular lateral segment. The LV lead was
      implanted at the optimum segment in 11 patients (at an adjacent segment in 2
      patients) achieving a QLV ratio of 0.82 +/- 0.09 (range 0.63-0.93) and 99.5 +/-
      0.6% match with intraprocedural mapping. CONCLUSION: Video-thoracoscopic LV lead
      implantation can be effectively and safely guided by epicardial QLV mapping. This
      strategy was highly successful in targeting the selected LV segment and resulted
      in significantly higher QLV ratios compared to an empirical midventricular
      lateral segment.

PMID- 24724627
TI  - Daidzein suppresses tumor necrosis factor-alpha induced migration and invasion by
      inhibiting hedgehog/Gli1 signaling in human breast cancer cells.
AB  - In breast cancer, the cytokine tumor necrosis factor-alpha (TNF-alpha) induces
      cell invasion, although the molecular basis of it has not been clearly
      elucidated. In this study, we investigated the role of daidzein in regulating TNF
      alpha induced cell invasion and the underlying molecular mechanisms. Daidzein
      inhibited TNF-alpha induced cellular migration and invasion in estrogen receptor
      (ER) negative MCF10DCIS.com human breast cancer cells. TNF-alpha activated
      Hedgehog (Hh) signaling by enhancing Gli1 nuclear translocation and
      transcriptional activity, which resulted in increased invasiveness; these effects
      were blocked by daidzein and the Hh signaling inhibitors, cyclopamine and
      vismodegib. Moreover, these compounds suppressed TNF-alpha induced matrix
      metalloproteinase (MMP)-9 mRNA expression and activity. Taken together, mammary
      tumor cell invasiveness was stimulated by TNF-alpha induced activation of Hh
      signaling; these effects were abrogated by daidzein, which suppressed Gli1
      activation, thereby inhibiting migration and invasion. 

PMID- 24724628
TI  - The potential advantages of digital PCR for clinical virology diagnostics.
AB  - Digital PCR (dPCR), a new nucleic acid amplification technology, offers several
      potential advantages over real-time or quantitative PCR (qPCR), the current
      workhorse of clinical molecular virology diagnostics. Several studies have
      demonstrated dPCR assays for human cytomegalovirus or HIV, which give more
      precise and reproducible results than qPCR assays without sacrificing
      sensitivity. Here we review the literature comparing dPCR and qPCR performance in
      viral molecular diagnostic assays and offer perspective on the future of dPCR in
      clinical virology diagnostics.

PMID- 24724629
TI  - Quantifying contextuality.
AB  - Contextuality is central to both the foundations of quantum theory and to the
      novel information processing tasks. Despite some recent proposals, it still faces
      a fundamental problem: how to quantify its presence? In this work, we provide a
      universal framework for quantifying contextuality. We conduct two complementary
      approaches: (i) the bottom-up approach, where we introduce a communication game,
      which grasps the phenomenon of contextuality in a quantitative manner; (ii) the
      top-down approach, where we just postulate two measures, relative entropy of
      contextuality and contextuality cost, analogous to existent measures of
      nonlocality (a special case of contextuality). We then match the two approaches
      by showing that the measure emerging from the communication scenario turns out to
      be equal to the relative entropy of contextuality. Our framework allows for the
      quantitative, resource-type comparison of completely different games. We give
      analytical formulas for the proposed measures for some contextual systems,
      showing in particular that the Peres-Mermin game is by order of magnitude more
      contextual than that of Klyachko et al. Furthermore, we explore properties of
      these measures such as monotonicity or additivity. 

PMID- 24724630
TI  - Objectivity in a noisy photonic environment through quantum state information
      broadcasting.
AB  - Recently, the emergence of classical objectivity as a property of a quantum state
      has been explicitly derived for a small object embedded in a photonic environment
      in terms of a spectrum broadcast form-a specific classically correlated state,
      redundantly encoding information about the preferred states of the object in the
      environment. However, the environment was in a pure state and the fundamental
      problem was how generic and robust is the conclusion. Here, we prove that despite
      the initial environmental noise, the emergence of the broadcast structure still
      holds, leading to the perceived objectivity of the state of the object. We also
      show how this leads to a quantum Darwinism-type condition, reflecting the
      classicality of proliferated information in terms of a limit behavior of the
      mutual information. Quite surprisingly, we find "singular points" of the
      decoherence, which can be used to faithfully broadcast a specific classical
      message through the noisy environment. 

PMID- 24724631
TI  - Demonstration of fold and cusp catastrophes in an atomic cloud reflected from an
      optical barrier in the presence of gravity.
AB  - We experimentally demonstrate first-order (fold) and second-order (cusp)
      catastrophes in the density of an atomic cloud reflected from an optical barrier
      in the presence of gravity and show their corresponding universal asymptotic
      behavior. These catastrophes, arising from classical dynamics, enable robust,
      field-free refocusing of an expanding atomic cloud with a wide velocity
      distribution. Specifically, the density attained at the cusp point in our
      experiment reached 65% of the peak density of the atoms in the trap prior to
      their release. We thereby add caustics to the various phenomena with parallels in
      optics that can be harnessed for manipulation of cold atoms. The structural
      stability of catastrophes provides inherent robustness against variations in the
      system's dynamics and initial conditions, making them suitable for manipulation
      of atoms under imperfect conditions and limited controllability. 

PMID- 24724632
TI  - Degree of non-Markovianity of quantum evolution.
AB  - We propose a new characterization of non-Markovian quantum evolution based on the
      concept of non-Markovianity degree. It provides an analog of a Schmidt number in
      the entanglement theory and reveals the formal analogy between quantum evolution
      and the entanglement theory: Markovian evolution corresponds to a separable state
      and the non-Markovian one is further characterized by its degree. It enables one
      to introduce a non-Markovianity witness-an analog of an entanglement witness, and
      a family of measures-an analog of Schmidt coefficients, and finally to
      characterize maximally non-Markovian evolution being an analog of the maximally
      entangled state. Our approach allows us to classify the non-Markovianity measures
      introduced so far in a unified rigorous mathematical framework. 

PMID- 24724633
TI  - Quantum metrology in open systems: dissipative Cramer-Rao bound.
AB  - Estimation of parameters is a pivotal task throughout science and technology. The
      quantum Cramer-Rao bound provides a fundamental limit of precision allowed to be
      achieved under quantum theory. For closed quantum systems, it has been shown how
      the estimation precision depends on the underlying dynamics. Here, we propose a
      general formulation for metrology scenarios in open quantum systems, aiming to
      relate the precision more directly to properties of the underlying dynamics. This
      feature may be employed to enhance an estimation precision, e.g., by quantum
      control techniques. Specifically, we derive a Cramer-Rao bound for a fairly large
      class of open system dynamics, which is governed by a (time-dependent) dynamical
      semigroup map. We illustrate the utility of this scenario through three examples.

PMID- 24724634
TI  - Constrained dynamics via the Zeno effect in quantum simulation: implementing non
      Abelian lattice gauge theories with cold atoms.
AB  - We show how engineered classical noise can be used to generate constrained
      Hamiltonian dynamics in atomic quantum simulators of many-body systems, taking
      advantage of the continuous Zeno effect. After discussing the general theoretical
      framework, we focus on applications in the context of lattice gauge theories,
      where imposing exotic, quasilocal constraints is usually challenging. We
      demonstrate the effectiveness of the scheme for both Abelian and non-Abelian
      gauge theories, and discuss how engineering dissipative constraints substitutes
      complicated, nonlocal interaction patterns by global coupling to laser fields. 

PMID- 24724635
TI  - Hyperfine splitting in positronium to O(alpha(7)m(e)): one photon annihilation
      contribution.
AB  - We present the complete result for the O(alpha7me) one photon annihilation
      contribution to the hyperfine splitting of the ground state energy levels in
      positronium. Numerically it increases the prediction of quantum electrodynamics
      by 217+/-1  kHz. 

PMID- 24724636
TI  - Collective coupling of a macroscopic number of single-molecule magnets with a
      microwave cavity mode.
AB  - We report the observation of strong coupling of a macroscopic ensemble of ~1016
      Fe8 molecular nanomagnets to the resonant mode of a microwave cavity. We use
      millimeter-wave spectroscopy to measure the splitting of the system's resonant
      frequency induced by the coupling between the spins and the cavity mode. The
      magnitude of this splitting is found to scale with ?N, where N is the number of
      collectively coupled spins. We control N by changing the system's temperature
      and, thereby, the populations of the relevant spin energy levels. Strong coupling
      is observed for two distinct transitions between spin energy states. Our results
      indicate that at low temperatures nearly all of the spins in the sample couple
      with the cavity's resonant mode even though there is substantial inhomogeneous
      broadening of the Fe8 spin resonances.

PMID- 24724637
TI  - Observation of topological structures in photonic quantum walks.
AB  - Phases of matter with nontrivial topological order are predicted to exhibit a
      variety of exotic phenomena, such as robust localized bound states in 1D systems,
      and edge states in 2D systems, which are expected to display spin helicity,
      immunity to backscattering, and weak antilocalization. In this Letter, we present
      an experimental observation of topological structures generated via the
      controlled implementation of two consecutive noncommuting rotations in photonic
      discrete-time quantum walks. The second rotation introduces valleylike Dirac
      points in the system, allowing us to create the nontrivial topological pattern.
      By choosing specific values for the rotations, it is possible to coherently drive
      the system between topological sectors characterized by different topological
      invariants. We probe the full topological landscape, demonstrating the emergence
      of localized bound states hosted at the topological boundaries, and the existence
      of extremely localized or delocalized non-Gaussian quantum states. Our results
      pave the way for the study of valley polarization and applications of topological
      mechanisms in robust optical-device engineering. 

PMID- 24724638
TI  - Entropic barriers for two-dimensional quantum memories.
AB  - Comprehensive no-go theorems show that information encoded over local two
      dimensional topologically ordered systems cannot support macroscopic energy
      barriers, and hence will not maintain stable quantum information at finite
      temperatures for macroscopic time scales. However, it is still well motivated to
      study low-dimensional quantum memories due to their experimental amenability.
      Here we introduce a grid of defect lines to Kitaev's quantum double model where
      different anyonic excitations carry different masses. This setting produces a
      complex energy landscape which entropically suppresses the diffusion of
      excitations that cause logical errors. We show numerically that entropically
      suppressed errors give rise to superexponential inverse temperature scaling and
      polynomial system size scaling for small system sizes over a low-temperature
      regime. Curiously, these entropic effects are not present below a certain low
      temperature. We show that we can vary the system to modify this bound and
      potentially extend the described effects to zero temperature. 

PMID- 24724639
TI  - Fault-tolerant measurement-based quantum computing with continuous-variable
      cluster states.
AB  - A long-standing open question about Gaussian continuous-variable cluster states
      is whether they enable fault-tolerant measurement-based quantum computation. The
      answer is yes. Initial squeezing in the cluster above a threshold value of 20.5
      dB ensures that errors from finite squeezing acting on encoded qubits are below
      the fault-tolerance threshold of known qubit-based error-correcting codes. By
      concatenating with one of these codes and using ancilla-based error correction,
      fault-tolerant measurement-based quantum computation of theoretically indefinite
      length is possible with finitely squeezed cluster states. 

PMID- 24724640
TI  - Experimental realization of multipartite entanglement of 60 modes of a quantum
      optical frequency comb.
AB  - We report the experimental realization and characterization of one 60-mode copy
      and of two 30-mode copies of a dual-rail quantum-wire cluster state in the
      quantum optical frequency comb of a bimodally pumped optical parametric
      oscillator. This is the largest entangled system ever created whose subsystems
      are all available simultaneously. The entanglement proceeds from the coherent
      concatenation of a multitude of Einstein, Podolsky, and Rosen pairs by a single
      beam splitter, a procedure which is also a building block for the realization of
      hypercubic-lattice cluster states for universal quantum computing. 

PMID- 24724641
TI  - Unconditional security of time-energy entanglement quantum key distribution using
      dual-basis interferometry.
AB  - High-dimensional quantum key distribution (HDQKD) offers the possibility of high
      secure-key rate with high photon-information efficiency. We consider HDQKD based
      on the time-energy entanglement produced by spontaneous parametric down
      conversion and show that it is secure against collective attacks. Its security
      rests upon visibility data-obtained from Franson and conjugate-Franson
      interferometers-that probe photon-pair frequency correlations and arrival-time
      correlations. From these measurements, an upper bound can be established on the
      eavesdropper's Holevo information by translating the Gaussian-state security
      analysis for continuous-variable quantum key distribution so that it applies to
      our protocol. We show that visibility data from just the Franson interferometer
      provides a weaker, but nonetheless useful, secure-key rate lower bound. To handle
      multiple-pair emissions, we incorporate the decoy-state approach into our
      protocol. Our results show that over a 200-km transmission distance in optical
      fiber, time-energy entanglement HDQKD could permit a 700-bit/sec secure-key rate
      and a photon information efficiency of 2 secure-key bits per photon coincidence
      in the key-generation phase using receivers with a 15% system efficiency. 

PMID- 24724642
TI  - Spin-current autocorrelations from single pure-state propagation.
AB  - We demonstrate that the concept of quantum typicality allows for significant
      progress in the study of real-time spin dynamics and transport in quantum
      magnets. To this end, we present a numerical analysis of the spin-current
      autocorrelation function of the antiferromagnetic and anisotropic spin-1/2
      Heisenberg chain as inferred from propagating only a single pure state, randomly
      chosen as a "typical" representative of the statistical ensemble. Comparing with
      existing time-dependent density-matrix renormalization group data, we show that
      typicality is fulfilled extremely well, consistent with an error of our approach,
      which is perfectly under control and vanishes in the thermodynamic limit. In the
      long-time limit, our results provide for a new benchmark for the enigmatic spin
      Drude weight, which we obtain from chains as long as L=33 sites, i.e., from
      Hilbert spaces of dimensions almost O(104) larger than in existing exact
      diagonalization studies. 

PMID- 24724643
TI  - Effectively universal behavior of rotating neutron stars in general relativity
      makes them even simpler than their Newtonian counterparts.
AB  - Recently, it was shown that slowly rotating neutron stars exhibit an interesting
      correlation between their moment of inertia I, their quadrupole moment Q, and
      their tidal deformation Love number lambda (the I-Love-Q relations),
      independently of the equation of state of the compact object. In the present
      Letter a similar, more general, universality is shown to hold true for all
      rotating neutron stars within general relativity; the first four multipole
      moments of the neutron star are related in a way independent of the nuclear
      matter equation of state we assume. By exploiting this relation, we can describe
      quite accurately the geometry around a neutron star with fewer parameters, even
      if we don't know precisely the equation of state. Furthermore, this universal
      behavior displayed by neutron stars could promote them to a more promising class
      of candidates (next to black holes) for testing theories of gravity. 

PMID- 24724644
TI  - Antimatter interferometry for gravity measurements.
AB  - We describe a light-pulse atom interferometer that is suitable for any species of
      atom and even for electrons and protons as well as their antiparticles, in
      particular, for testing the Einstein equivalence principle with antihydrogen. The
      design obviates the need for resonant lasers through far-off resonant Bragg beam
      splitters and makes efficient use of scarce atoms by magnetic confinement and
      atom recycling. We expect to reach an initial accuracy of better than 1% for the
      acceleration of the free fall of antihydrogen, which can be improved to the part
      per million level. 

PMID- 24724646
TI  - Experimental determination of the antineutrino spectrum of the fission products
      of U238.
AB  - An experiment was performed at the scientific neutron source FRM II in Garching
      to determine the cumulative antineutrino spectrum of the fission products of
      U238. Target foils of natural uranium were irradiated with a thermal and a fast
      neutron beam and the emitted beta spectra were recorded with a gamma-suppressing
      electron telescope. The obtained beta spectrum of the fission products of U235
      was normalized to the data of the magnetic spectrometer BILL. This method
      strongly reduces systematic errors in the U238 measurement. The beta spectrum of
      U238 was converted into the corresponding nu-e spectrum. The final nu-e spectrum
      is given in 250 keV bins in the range from 2.875 to 7.625 MeV with an energy
      dependent error of 3.5% at 3 MeV, 7.6% at 6 MeV, and ?14% at energies ?7  MeV
      (68% confidence level). Furthermore, an energy-independent uncertainty of ~3.3%
      due to the absolute normalization is added. Compared to the generally used
      summation calculations, the obtained spectrum reveals a spectral distortion of
      ~10% but returns the same value for the mean cross section per fission for the
      inverse beta decay. 

PMID- 24724647
TI  - Beyond the spin model approximation for Ramsey spectroscopy.
AB  - Ramsey spectroscopy has become a powerful technique for probing nonequilibrium
      dynamics of internal (pseudospin) degrees of freedom of interacting systems. In
      many theoretical treatments, the key to understanding the dynamics has been to
      assume the external (motional) degrees of freedom are decoupled from the
      pseudospin degrees of freedom. Determining the validity of this approximation
      known as the spin model approximation-has not been addressed in detail. Here we
      shed light in this direction by calculating Ramsey dynamics exactly for two
      interacting spin-1/2 particles in a harmonic trap. We focus on s-wave-interacting
      fermions in quasi one- and two-dimensional geometries. We find that in one
      dimension the spin model assumption works well over a wide range of
      experimentally relevant conditions, but can fail at time scales longer than those
      set by the mean interaction energy. Surprisingly, in two dimensions a modified
      version of the spin model is exact to first order in the interaction strength.
      This analysis is important for a correct interpretation of Ramsey spectroscopy
      and has broad applications ranging from precision measurements to quantum
      information and to fundamental probes of many-body systems. 

PMID- 24724648
TI  - Tunable resonant and nonresonant interactions between a phase qubit and LC
      resonator.
AB  - We use a flux-biased radio frequency superconducting quantum interference device
      (rf SQUID) with an embedded flux-biased direct current SQUID to generate strong
      resonant and nonresonant tunable interactions between a phase qubit and a lumped
      element resonator. The rf SQUID creates a tunable magnetic susceptibility between
      the qubit and resonator providing resonant coupling strengths from zero to near
      the ultrastrong coupling regime. By modulating the magnetic susceptibility,
      nonresonant parametric coupling achieves rates >100  MHz. Nonlinearity of the
      magnetic susceptibility also leads to parametric coupling at the subharmonics of
      the qubit-resonator detuning. 

PMID- 24724649
TI  - Nonlinear oscillations and bifurcations in silicon photonic microresonators.
AB  - Silicon microdisks are optical resonators that can exhibit surprising nonlinear
      behavior. We present a new analysis of the dynamics of these resonators
      elucidating the mathematical origin of spontaneous oscillations and deriving
      predictions for observed phenomena such as a frequency comb spectrum with MHz
      scale repetition rate. We test predictions through laboratory experiment and
      numerical simulation. 

PMID- 24724650
TI  - Dependence of laser-driven coherent synchrotron emission efficiency on pulse
      ellipticity and implications for polarization gating.
AB  - The polarization dependence of laser-driven coherent synchrotron emission
      transmitted through thin foils is investigated experimentally. The harmonic
      generation process is seen to be almost completely suppressed for circular
      polarization opening up the possibility of producing isolated attosecond pulses
      via polarization gating. Particle-in-cell simulations suggest that current laser
      pulses are capable of generating isolated attosecond pulses with high pulse
      energies. 

PMID- 24724651
TI  - Fundamental limits to extinction by metallic nanoparticles.
AB  - We show that there are shape-independent upper bounds to the extinction cross
      section per unit volume of dilute, randomly arranged nanoparticles, given only
      material permittivity. Underlying the limits are restrictive sum rules that
      constrain the distribution of quasistatic eigenvalues. Surprisingly, optimally
      designed spheroids, with only a single quasistatic degree of freedom, reach the
      upper bounds for four permittivity values. Away from these permittivities, we
      demonstrate computationally optimized structures that surpass spheroids and
      approach the fundamental limits. 

PMID- 24724652
TI  - Time-reversal generation of rogue waves.
AB  - The formation of extreme localizations in nonlinear dispersive media can be
      explained and described within the framework of nonlinear evolution equations,
      such as the nonlinear Schrodinger equation (NLS). Within the class of exact NLS
      breather solutions on a finite background, which describe the modulational
      instability of monochromatic wave trains, the hierarchy of rational solutions
      localized in both time and space is considered to provide appropriate prototypes
      to model rogue wave dynamics. Here, we use the time-reversal invariance of the
      NLS to propose and experimentally demonstrate a new approach to constructing
      strongly nonlinear localized waves focused in both time and space. The potential
      applications of this time-reversal approach include remote sensing and motivated
      analogous experimental analysis in other nonlinear dispersive media, such as
      optics, Bose-Einstein condensates, and plasma, where the wave motion dynamics is
      governed by the NLS. 

PMID- 24724653
TI  - Turbulent boundary layer in high Rayleigh number convection in air.
AB  - Flow visualizations and particle image velocimetry measurements in the boundary
      layer of a Rayleigh-Benard experiment are presented for the Rayleigh number
      Ra=1.4*1010. Our visualizations indicate that the appearance of the flow
      structures is similar to ordinary (isothermal) turbulent boundary layers. Our
      particle image velocimetry measurements show that vorticity with both positive
      and negative sign is generated and that the smallest flow structures are 1 order
      of magnitude smaller than the boundary layer thickness. Additional local
      measurements using laser Doppler velocimetry yield turbulence intensities up to
      I=0.4 as in turbulent atmospheric boundary layers. From our observations, we
      conclude that the convective boundary layer becomes turbulent locally and
      temporarily although its Reynolds number Re~200 is considerably smaller than the
      value 420 underlying existing phenomenological theories. We think that, in
      turbulent Rayleigh-Benard convection, the transition of the boundary layer
      towards turbulence depends on subtle details of the flow field and is therefore
      not universal. 

PMID- 24724654
TI  - Two-color laser-ionization injection.
AB  - A method is proposed to generate femtosecond, ultralow emittance (~10-8  m rad),
      electron beams in a laser-plasma accelerator using two lasers of different
      colors. A long-wavelength pump pulse, with a large ponderomotive force and small
      peak electric field, excites a wake without fully ionizing a high-Z gas. A short
      wavelength injection pulse, with a small ponderomotive force and large peak
      electric field, copropagating and delayed with respect to the pump laser, ionizes
      a fraction of the remaining bound electrons at a trapping wake phase, generating
      an electron beam that is accelerated in the wake. 

PMID- 24724655
TI  - Observation of the L-H confinement bifurcation triggered by a turbulence-driven
      shear flow in a tokamak plasma.
AB  - Comprehensive 2D turbulence and eddy flow velocity measurements on DIII-D
      demonstrate a rapidly increasing turbulence-driven shear flow that develops ~100 
      MUs prior to the low-confinement (L mode) to high-confinement (H mode) transition
      and appears to trigger it. These changes are localized to a narrow layer 1-2 cm
      inside the magnetic boundary. Increasing heating power increases the Reynolds
      stress, the energy transfer from turbulence to the poloidal flow, and the edge
      flow shearing rate that then exceeds the decorrelation rate, suppressing
      turbulence and triggering the transition. 

PMID- 24724656
TI  - Helicity-flux-driven alpha effect in laboratory and astrophysical plasmas.
AB  - The constraint imposed by magnetic helicity conservation on the alpha effect is
      considered for both magnetically and flow dominated self-organizing plasmas.
      Direct numerical simulations are presented for a dominant contribution to the
      alpha effect, which can be cast in the functional form of a total divergence of
      an averaged helicity flux, called the helicity-flux-driven alpha (Halpha) effect.
      Direct numerical simulations of the Halpha effect are presented for two examples
      the magnetically dominated toroidal plasma unstable to tearing modes, and the
      flow-dominated accretion disk. 

PMID- 24724657
TI  - Structure of nanocrystalline Ti3C2 MXene using atomic pair distribution function.
AB  - The structures of nanocrystalline pristine, potassium hydroxide and sodium
      acetate intercalated new two-dimensional materials Ti3C2 MXenes were studied
      using the x-ray atomic pair distribution function technique. Pristine MXene has a
      hexagonal structure with a=b=3.0505(5)  A, c=19.86(2)  A (S.G. P63/mmc No. 194).
      Both hydroxyl and fluoride terminating species are present. The intercalation of
      K+ or Na+ ions expands the Ti3C2 layers perpendicular to the planes but shrinks
      the in-plane a and b lattice parameters. 

PMID- 24724658
TI  - Anharmonic damping of terahertz acoustic waves in a network glass and its effect
      on the density of vibrational states.
AB  - We report the observation, by means of high-resolution inelastic x-ray
      scattering, of an unusually large temperature dependence of the sound attenuation
      of a network glass at terahertz frequency, an unprecedentedly observed
      phenomenon. The anharmonicity can be ascribed to the interaction between the
      propagating acoustic wave and the bath of thermal vibrations. At low temperatures
      the sound attenuation follows a Rayleigh-Gans scattering law. As the temperature
      is increased the anharmonic process sets in, resulting in an almost quadratic
      frequency dependence of the damping in the entire frequency range. We show that
      the temperature variation of the sound damping accounts quantitatively for the
      temperature dependence of the density of vibrational states. 

PMID- 24724645
TI  - Jet-hadron correlations in ?[s(NN)]=200  GeV p+p and central Au+Au collisions.
AB  - Azimuthal angular correlations of charged hadrons with respect to the axis of a
      reconstructed (trigger) jet in Au+Au and p+p collisions at ?[s(NN)]=200  GeV in
      STAR are presented. The trigger jet population in Au+Au collisions is biased
      toward jets that have not interacted with the medium, allowing easier matching of
      jet energies between Au+Au and p+p collisions while enhancing medium effects on
      the recoil jet. The associated hadron yield of the recoil jet is significantly
      suppressed at high transverse momentum (pTassoc) and enhanced at low pTassoc in
      0%-20% central Au+Au collisions compared to p+p collisions, which is indicative
      of medium-induced parton energy loss in ultrarelativistic heavy-ion collisions.

PMID- 24724659
TI  - Determination of the origin and magnitude of logarithmic finite-size effects on
      interfacial tension: role of interfacial fluctuations and domain breathing.
AB  - The ensemble-switch method for computing wall excess free energies of condensed
      matter is extended to estimate the interface free energies between coexisting
      phases very accurately. By this method, system geometries with linear dimensions
      L parallel and Lz perpendicular to the interface with various boundary conditions
      in the canonical or grand canonical ensemble can be studied. Using two- and three
      dimensional Ising models, the nature of the occurring logarithmic finite-size
      corrections is studied. It is found crucial to include interfacial fluctuations
      due to "domain breathing." 

PMID- 24724660
TI  - Evidence of liquid-liquid transition in triphenyl phosphite from time-resolved
      light scattering experiments.
AB  - Here, we study the phase transition kinetics in a supercooled liquid state of
      triphenyl phosphite by means of time-resolved polarized and depolarized light
      scattering to address a long-standing controversy on its mechanism, i.e., whether
      the phenomenon is primarily induced by liquid-liquid transition (LLT) or by
      nanocrystal formation. We find that the polarized scattering intensity exhibits a
      peak as a function of time, and its low wave number limit is nonzero for any
      annealing temperatures, both of which strongly indicate the nonconserved nature
      of an order parameter governing the transition. We also observe evolution of
      depolarized scattering. Above the spinodal temperature TSD, the depolarized
      scattering intensity monotonically increases with time since it is dominated by
      scattering from nanocrystallites, which are continuously formed during the
      process. Below TSD, on the other hand, it exhibits a distinct peak as a function
      of time as the polarized scattering intensity does. This appearance of the peak
      suggests that dielectric tensor fluctuations responsible for the depolarized
      scattering mainly come from isotropic density fluctuations and not from
      nanocrystallites, supporting the occurrence of LLT. 

PMID- 24724661
TI  - Unveiling the mechanism of water partial dissociation on Ru(0001).
AB  - We have studied the mechanism of the partial dissociation of water on Ru(0001) by
      high resolution scanning tunneling microscopy (STM). The thermal evolution of
      water at submonolayer coverage has been tracked in the 110-145 K temperature
      range to identify the precursor structures for the partial dissociation. These
      were found to consist of hexagons arranged in thin stripes aligned along the
      close packed Ru [21-1-0] directions. The partially dissociated phase, on the
      other hand, contains a mixture of H2O and OH hexagons arranged into wider stripes
      and rotated by 30 degrees  with respect to the intact water stripes. The atomic
      structure of both types of stripes is determined with the aid of density
      functional theory and STM simulations, providing insights into the partial
      dissociation reaction path. The reaction is found to be exothermic by around 0.4
      eV and initiating at the edges of the intact water stripes. Hydrogen atoms, from
      water dissociation or already present at the surface, are found to play an
      important role in the kinetics of the reactions. 

PMID- 24724662
TI  - Morphology of monolayer MgO films on Ag(100): switching from corrugated islands
      to extended flat terraces.
AB  - The ability to engineer nearly perfect ultrathin oxide layers, up to the limit of
      monolayer thickness, is a key issue for nanotechnological applications. Here we
      face the difficult and important case of ultrathin MgO films on Ag(100), for
      which no extended and well-ordered layers could thus far be produced in the
      monolayer limit. We demonstrate that their final morphology depends not only on
      the usual growth parameters (crystal temperature, metal flux, and oxygen partial
      pressure), but also on aftergrowth treatments controlling so far neglected
      thermodynamics constraints. We thus succeed in tuning the shape of the oxide
      films from irregular, nanometer-sized, monolayer-thick islands to slightly
      larger, perfectly squared, bilayer islands, to extended monolayers limited
      apparently only by substrate steps. 

PMID- 24724663
TI  - Atomic-scale quantification of grain boundary segregation in nanocrystalline
      material.
AB  - Grain boundary segregation leads to nanoscale chemical variations that can alter
      a material's performance by orders of magnitude (e.g., embrittlement). To
      understand this phenomenon, a large number of grain boundaries must be
      characterized in terms of both their five crystallographic interface parameters
      and their atomic-scale chemical composition. We demonstrate how this can be
      achieved using an approach that combines the accuracy of structural
      characterization in transmission electron microscopy with the 3D chemical
      sensitivity of atom probe tomography. We find a linear trend between carbon
      segregation and the misorientation angle omega for low-angle grain boundaries in
      ferrite, which indicates that omega is the most influential crystallographic
      parameter in this regime. However, there are significant deviations from this
      linear trend indicating an additional strong influence of other crystallographic
      parameters (grain boundary plane, rotation axis). For high-angle grain
      boundaries, no general trend between carbon excess and omega is observed; i.e.,
      the grain boundary plane and rotation axis have an even higher influence on the
      segregation behavior in this regime. Slight deviations from special grain
      boundary configurations are shown to lead to unexpectedly high levels of
      segregation. 

PMID- 24724664
TI  - Direct dynamical evidence for the spin glass lower critical dimension 2<d(l)<3.
AB  - A dynamical method is introduced to study the effect of dimensionality on phase
      transitions. Direct experimental measurements for the lower critical dimension
      for spin glasses is provided as an example. The method makes use of the spin
      glass correlation length xi(t,T). Once nucleated, it can become comparable to
      sample dimensions in convenient time and temperature ranges. Thin films of
      amorphous Ge:Mn alloys were prepared with thickness L~15.5  nm. Conventional
      behavior is observed as long as xi(t,T)<L. At the measurement time tco, when
      xi(tco,T)~L, the time dependence is observed to cross over to exponential. These
      results are interpreted using spin glass dynamics, and are consistent with a
      lower critical dimension for spin glasses, dl, between 2<dl<3. 

PMID- 24724665
TI  - Majorana bound states in two-channel time-reversal-symmetric nanowire systems.
AB  - We consider time-reversal-symmetric two-channel semiconducting quantum wires
      proximity coupled to a conventional s-wave superconductor. We analyze the
      requirements for a nontrivial topological phase and find that the necessary
      conditions are (1) the determinant of the pairing matrix in channel space must be
      negative, (2) inversion symmetry must be broken, and (3) the two channels must
      have different spin-orbit couplings. The first condition can be implemented in
      semiconducting nanowire systems where interactions suppress intra-channel
      pairing, while the inversion symmetry can be broken by tuning the chemical
      potentials of the channels. For the case of collinear spin-orbit directions, we
      find a general expression for the topological invariant by block diagonalization
      into two blocks with chiral symmetry only. By projection to the low-energy
      sector, we solve for the zero modes explicitly and study the details of the gap
      closing, which in the general case happens at finite momenta. 

PMID- 24724666
TI  - Coherent control to prepare an InAs quantum dot for spin-photon entanglement.
AB  - We optically generated an electronic state in a single InAs/GaAs self-assembled
      quantum dot that is a precursor to the deterministic entanglement of the spin of
      the electron with an emitted photon in the proposal of W. Yao, R.-B. Liu, and L.
      J. Sham [Phys. Rev. Lett. 95, 030504 (2005). A superposition state is prepared by
      optical pumping to a pure state followed by an initial pulse. By modulating the
      subsequent pulse arrival times and precisely controlling them using
      interferometric measurement of path length differences, we are able to implement
      a coherent control technique to selectively drive exactly one of the two
      components of the superposition to the ground state. This optical transition
      contingent on spin was driven with the same broadband pulses that created the
      superposition through the use of a two pulse coherent control sequence. A final
      pulse affords measurement of the coherence of this "preentangled" state.

PMID- 24724667
TI  - Low-temperature transport properties of photogenerated charges in organic
      materials.
AB  - We report a new experimental method to measure the localization length of
      photogenerated carriers in an organic donor-acceptor photovoltaic blend by
      comparing their dielectric and electron spin-resonance susceptibilities, which
      are simultaneously measured by monitoring the resonance frequency of a
      superconducting resonator. We show that at cryogenic temperatures excitons are
      dissociated into long lived states, but that these are confined within a
      separation of around 4 nm. We determine the Debye and recombination times,
      showing the coexistence of a fast electrical response corresponding to
      delocalized motion, with glasslike recombination kinetics. 

PMID- 24724668
TI  - Tuning the influence of microscopic decoherence on the superconducting proximity
      effect in a graphene Andreev interferometer.
AB  - We discuss transport measurements through graphene Andreev interferometers
      exhibiting reentrance of the superconducting proximity effect. We observe that at
      high gate voltage (VBG) the energy dependence of the Andreev conductance
      oscillations exhibits a scaling in agreement with theoretical expectations, which
      breaks down at low VBG, when the Fermi energy approaches the charge neutrality
      point. The phenomenon is a manifestation of single particle dephasing that
      increasingly limits the propagation of superconducting correlations away from the
      superconductor-graphene interface. Our work addresses the interplay between
      microscopic decoherence and superconductivity, and shows that graphene provides a
      useful experimental platform to investigate unexplored regimes and phenomena in
      the superconducting proximity effect. 

PMID- 24724669
TI  - Broken SU(4) symmetry and the fractional quantum Hall effect in graphene.
AB  - We describe a variational theory for incompressible ground states and charge gaps
      in the N=0 Landau level of graphene that accounts for the fourfold Landau level
      degeneracy and the short-range interactions that break SU(4) spin-valley
      invariance. Our approach explains the experimental finding that gaps at odd
      numerators are weak for 1<|nu|<2 and strong for 0<|nu|<1. We find that in the
      SU(4) invariant case the incompressible ground state at |nu|=1/3 is a three
      component incompressible state, not the Laughlin state, and discuss the
      competition between these two states in the presence of SU(4) spin-valley
      symmetry-breaking terms. 

PMID- 24724670
TI  - Ultrashort single-wall carbon nanotubes reveal field-emission coulomb blockade
      and highest electron-source brightness.
AB  - We present here well-defined Coulomb staircases using an original field-emission
      experiment on several individual in situ-grown single-wall carbon nanotubes. A
      unique in situ process was applied nine times to progressively shorten one single
      wall carbon nanotube down to ?10  nm, which increased the oscillations periods
      from 5.5 to 80 V, the temperature for observable Coulomb staircase to 1100 K and
      the currents to 1.8  MUA. This process led to the brightest electron source ever
      reported [9*1011  A/(str m2 V)]. 

PMID- 24724671
TI  - Fractional Chern insulators with strong interactions that far exceed band gaps.
AB  - We study two models for spinless fermions featuring topologically nontrivial
      bands characterized by Chern numbers C=+/-1 at fractional filling. Using exact
      diagonalization, we show that, even for infinitely strong nearest-neighbor
      repulsion, the ground states of these models belong to the recently discovered
      class of quantum liquids called fractional Chern insulators (FCI). Thus, we
      establish that FCI states can arise even if interaction strengths are arbitrarily
      larger than the noninteracting band gap, going beyond the limits in which FCI
      states have been previously studied. The strong-coupling FCI states, therefore,
      depart from the usual isolated-band picture that parallels the fractional quantum
      Hall effect in Landau levels and demonstrate how a topologically ordered state
      can arise in a truly multiband system. 

PMID- 24724672
TI  - Doping dependence of the anisotropic quasiparticle interference in NaFe(1
      x)Co(x)As iron-based superconductors.
AB  - We use scanning tunneling microscopy to investigate the doping dependence of
      quasiparticle interference (QPI) in NaFe1-xCoxAs iron-based superconductors. The
      goal is to study the relation between nematic fluctuations and Cooper pairing. In
      the parent and underdoped compounds, where fourfold rotational symmetry is broken
      macroscopically, the QPI patterns reveal strong rotational anisotropy. At optimal
      doping, however, the QPI patterns are always fourfold symmetric. We argue this
      implies small nematic susceptibility and, hence, insignificant nematic
      fluctuation in optimally doped iron pnictides. Since TC is the highest this
      suggests nematic fluctuation is not a prerequistite for strong Cooper pairing. 

PMID- 24724673
TI  - Spin-orbital entanglement and the breakdown of singlets and triplets in Sr2RuO4
      revealed by spin- and angle-resolved photoemission spectroscopy.
AB  - Spin-orbit coupling has been conjectured to play a key role in the low-energy
      electronic structure of Sr2RuO4. By using circularly polarized light combined
      with spin- and angle-resolved photoemission spectroscopy, we directly measure the
      value of the effective spin-orbit coupling to be 130+/-30  meV. This is even
      larger than theoretically predicted and comparable to the energy splitting of the
      dxy and dxz,yz orbitals around the Fermi surface, resulting in a strongly
      momentum-dependent entanglement of spin and orbital character in the electronic
      wavefunction. As demonstrated by the spin expectation value ?sk?.s-k?? calculated
      for a pair of electrons with zero total momentum, the classification of the
      Cooper pairs in terms of pure singlets or triplets fundamentally breaks down,
      necessitating a description of the unconventional superconducting state of
      Sr2RuO4 in terms of these newly found spin-orbital entangled eigenstates. 

PMID- 24724674
TI  - Persistence of the superconducting condensate far above the critical temperature
      of YBa2(Cu,Zn)3O(y) revealed by c-axis optical conductivity measurements for
      several Zn concentrations and carrier doping levels.
AB  - The superconductivity precursor phenomena in high temperature cuprate
      superconductors is studied by direct measurements of the superconducting
      condensate with the use of the c-axis optical conductivity of YBa2(Cu1-xZnx)3Oy
      for several doping levels (p) as well as for several Zn concentrations. Both the
      real and imaginary parts of the optical conductivity clearly show that the
      superconducting carriers persist up to the high temperatures Tp that is higher
      than the critical temperature Tc but lower than the pseudogap temperature T*. Tp
      increases with reducing doping level like T*, but decreases with Zn substitution
      unlike T*. 

PMID- 24724675
TI  - Dissipation in ultrahigh quality factor SiN membrane resonators.
AB  - We study the mechanical properties of stoichiometric SiN resonators through a
      combination of spectroscopic and interferometric imaging techniques. At room
      temperature, we demonstrate ultrahigh quality factors of 5*107 and a f*Q product
      of 1*1014  Hz. To our knowledge, these correspond to the largest values yet
      reported for mesoscopic flexural resonators. Through a comprehensive study of the
      limiting dissipation mechanisms as a function of resonator and substrate
      geometry, we identify radiation loss through the supporting substrate as the
      dominant loss process. In addition to pointing the way towards higher quality
      factors through optimized substrate designs, our work realizes an enabling
      platform for the observation and control of quantum behavior in a macroscopic
      mechanical system. 

PMID- 24724676
TI  - Standing spin waves in ultrathin magnetic films: a method to test for layer
      dependent exchange coupling.
AB  - We introduce a method to test theoretical models for the layer dependence of
      exchange coupling constants in ultrathin magnetic films. The method is based on
      the observation of high-energy and high-momentum standing spin wave modes using
      high-resolution electron energy loss spectroscopy. Experimental data are
      presented for 5-8 layers of fcc cobalt deposited on Cu(100). The power of the
      method is illustrated by comparison to two theoretical studies predicting rather
      different results concerning the ratio of the interlayer and intralayer exchange
      coupling constants near the surface. Only the theory with a large interlayer
      coupling shows sufficient energy spreading in the layer dependence of the
      dispersion curves to match the experimental data. We furthermore discuss the
      reason for the surprising success of the simple nearest-neighbor Heisenberg model
      with a single exchange constant matched to experiment. 

PMID- 24724677
TI  - Quantum phase diagram of the triangular-lattice XXZ model in a magnetic field.
AB  - The triangular lattice of S=1/2 spins with XXZ anisotropy is a ubiquitous model
      for various frustrated systems in different contexts. We determine the quantum
      phase diagram of the model in the plane of the anisotropy parameter and the
      magnetic field by means of a large-size cluster mean-field method with a scaling
      scheme. We find that quantum fluctuations break up the nontrivial continuous
      degeneracy into two first-order phase transitions. In between the two transition
      boundaries, the degeneracy-lifting results in the emergence of a new coplanar
      phase not predicted in the classical counterpart of the model. We suggest that
      the quantum phase transition to the nonclassical coplanar state can be observed
      in triangular-lattice antiferromagnets with large easy-plane anisotropy or in the
      corresponding optical-lattice systems. 

PMID- 24724678
TI  - Geometric mutual information at classical critical points.
AB  - A practical use of the entanglement entropy in a 1D quantum system is to identify
      the conformal field theory describing its critical behavior. It is exactly
      (c/3)lnl for an interval of length l in an infinite system, where c is the
      central charge of the conformal field theory. Here we define the geometric mutual
      information, an analogous quantity for classical critical points. We compute this
      for 2D conformal field theories in an arbitrary geometry, and show in particular
      that for a rectangle cut into two rectangles, it is proportional to c. This makes
      it possible to extract c in classical simulations, which we demonstrate for the
      critical Ising and three-state Potts models. 

PMID- 24724679
TI  - Spin-nematic interaction in the multiferroic compound Ba2CoGe2O7.
AB  - We demonstrate the existence of the spin-nematic interactions in an easy-plane
      type antiferromagnet Ba2CoGe2O7 by exploring the magnetic anisotropy and spin
      dynamics. The combination of neutron scattering and magnetic susceptibility
      measurements reveals that the origin of the in-plane anisotropy is an antiferro
      type interaction of the spin-nematic operator. The relation between the nematic
      operator and the electric polarization in the ligand symmetry of this compound is
      presented. The introduction of the spin-nematic interaction is useful to
      understand the physics of spin and electric dipole in multiferroic compounds. 

PMID- 24724680
TI  - Hyperferroelectrics: proper ferroelectrics with persistent polarization.
AB  - All known proper ferroelectrics are unable to polarize normal to a surface or
      interface if the resulting depolarization field is unscreened, but there is no
      fundamental principle that enforces this behavior. In this work, we introduce
      hyperferroelectrics, a new class of proper ferroelectrics which polarize even
      when the depolarization field is unscreened, this condition being equivalent to
      instability of a longitudinal optic mode in addition to the transverse-optic-mode
      instability characteristic of proper ferroelectrics. We use first-principles
      calculations to show that several recently discovered hexagonal ferroelectric
      semiconductors have this property, and we examine its consequences both in the
      bulk and in a superlattice geometry. 

PMID- 24724681
TI  - Dynamics of the force exchanged between membrane inclusions.
AB  - We study the dynamical response of a fluid membrane to the sudden conformation
      change of active inclusions linearly coupled to the membrane curvature. The
      mutual force between two inclusions triggered simultaneously is shown to exhibit
      a transient maximum much larger than the equilibrium force. Even in the presence
      of tension, this dynamical interaction is long range over distances much larger
      than the correlation length. We derive the scaling laws describing these
      phenomena analytically, and we stress the importance of the damping due to
      intermonolayer friction. 

PMID- 24724682
TI  - Interactions between nanofibers in fiber-surfactant suspensions: theory of
      corresponding distances.
AB  - We present the theory of corresponding distances for interactions mediated by
      soft nanostructures in fibrous materials. Based on the fundamental understanding
      of the mechanism that determines the internal structure of the soft component,
      our theory allows us to predict the entire force field mediated by the soft
      component for any angle and distance between the fibers from a single simulation
      or a single experiment. This replaces hundreds of simulations by just one which
      enables the routine computation of complete fiber-soft-fiber force fields by high
      level methods, such as atomistic simulations, and thereby amounts to a true step
      advancement for soft nanotechnology. 

PMID- 24724683
TI  - Chaotic induced-charge electro-osmosis.
AB  - We present direct numerical simulations of the coupled Poisson-Nernst-Planck and
      Navier-Stokes equations for an electrolyte around a polarizable cylinder subject
      to an external electric field. For high fields, a novel chaotic flow phenomenon
      is discovered. Our calculations indicate significant improvement in the
      prediction of the mean flow relative to standard asymptotic models. These results
      open possibilities for chaos-enhanced mixing in microdevices and provide insight
      into barriers to efficient electrokinetic micropumps with broad applications in
      electrochemical and lab-on-a-chip systems. 

PMID- 24724684
TI  - Off-equilibrium surface tension in colloidal suspensions.
AB  - We study the fingering instability of the interface between two miscible fluids,
      a colloidal suspension and its own solvent. The temporal evolution of the
      interface in a Hele-Shaw cell is found to be governed by the competition between
      the nonlinear viscosity of the suspension and an off-equilibrium, effective
      surface tension Gammae. By studying suspensions in a wide range of volume
      fractions, PhiC, we show that Gammae~PhiC2, in agreement with Korteweg's theory
      for miscible fluids. The surface tension exhibits an anomalous increase with
      particle size, which we account for using entropy arguments. 

PMID- 24724685
TI  - Collective surfing of chemically active particles.
AB  - We study theoretically the collective dynamics of immotile particles bound to a
      2D surface atop a 3D fluid layer. These particles are chemically active and
      produce a chemical concentration field that creates surface-tension gradients
      along the surface. The resultant Marangoni stresses create flows that carry the
      particles, possibly concentrating them. For a 3D diffusion-dominated
      concentration field and Stokesian fluid we show that the surface dynamics of
      active particle density can be determined using nonlocal 2D surface operators.
      Remarkably, we also show that for both deep or shallow fluid layers this surface
      dynamics reduces to the 2D Keller-Segel model for the collective chemotactic
      aggregation of slime mold colonies. Mathematical analysis has established that
      the Keller-Segel model can yield finite-time, finite-mass concentration
      singularities. We show that such singular behavior occurs in our finite-depth
      system, and study the associated 3D flow structures. 

PMID- 24724686
TI  - Comment on "State-dependent electron delocalization dynamics at the solute
      solvent interface: soft-x-ray absorption spectroscopy and ab initio
      calculations".

PMID- 24724687
TI  - Comment on "State-dependent electron delocalization dynamics at the solute
      solvent interface: soft-x-ray absorption spectroscopy and ab initio
      calculations".

PMID- 24724688
TI  - Bokarev et al. Reply.

PMID- 24724689
TI  - Comment on "Spin-gradient-driven light amplification in a quantum plasma".

PMID- 24724690
TI  - Braun, Asenjo, and Mahajan reply:.

PMID- 24724691
TI  - Empirical research evaluating non-traditional approaches to managing sleep
      problems in children with autism.
AB  - OBJECTIVE: This paper examines the efficacy of non-behavioural and non
      pharmacological approaches to the treatment of sleep disturbance in individuals
      with autism spectrum disorder. METHODS: A systematic search of electronic
      databases and reference lists identified eight studies that met inclusion
      criteria. Studies were evaluated according to (a) treatment used, (b)
      participants, (c) experimental design, (d) baseline measures, (e) dependent
      variables, (f) follow-up measures, (g) reliability and treatment integrity, (h)
      results and certainty of evidence and (i) implications for treatment. RESULTS:
      Positive outcomes were reported for the use of massage therapy and vitamin
      supplements. Aromatherapy was reported to have no effect on sleep. No studies
      were found that examined other non-traditional treatment approaches, nor did any
      of the studies provide conclusive evidence. CONCLUSIONS: The limited corpus of
      evidence and the methodological limitations suggests that the efficacy of non
      traditional approaches to treatment of sleep problems in individuals with autism
      is yet to be demonstrated.

PMID- 24724692
TI  - N-substituted 2-aminobiphenylpalladium methanesulfonate precatalysts and their
      use in C-C and C-N cross-couplings.
AB  - A series of phosphine-ligated palladium precatalysts based on N-methyl- and N
      phenyl-2-aminobiphenyl have been developed. Substitution at the nitrogen center
      prevents the presence of traces of aminobiphenyls that contain a free -NH2 group
      from contaminating cross-coupling products. These precatalysts produce N
      substituted carbazoles upon activation, which cannot consume starting materials.
      These precatalysts were efficiently generated from 2-aminobiphenyl with minimal
      purification and found to be highly effective in Suzuki-Miyaura and C-N cross
      coupling reactions. 

PMID- 24724700
TI  - The characteristics of healthy adults with hardly palpable vein--Relations
      between easy venous palpation and physical factors.
AB  - This study aimed to investigate relations between ease of venous palpation and
      various venous factors, and to elucidate characteristics of hardly palpable
      veins. Healthy adult volunteers (n = 110) were enrolled. The ease of venous
      palpation was scored from 0: impalpable to 3: well palpable. Venous factors,
      namely venous depth, elevation, area and minimal pressure that starts to collapse
      vein, were measured using an ultrasonography before and after tourniquet
      inflation at 60 mmHg for 60 s. Tourniquet inflation significantly increased the
      venous area and venous palpation score. The four venous factors correlated
      significantly with venous palpation score with the following correlation
      coefficient: Depth (r = -0.542), Elevation (0.486), area (0.258) and start-to
      collapse pressure (-0.220). The characteristics of hardly palpable veins were
      small size, deep location and little elevation. Although vasodilatation
      facilitated venous palpation, venous depth and elevation were also important and
      should be included in future studies in which vasodilatation methods are
      evaluated. 

PMID- 24724693
TI  - Agomelatine: mechanism of action and pharmacological profile in relation to
      antidepressant properties.
AB  - Agomelatine behaves both as a potent agonist at melatonin MT1 and MT2 receptors
      and as a neutral antagonist at 5-HT2C receptors. Accumulating evidence in a broad
      range of experimental procedures supports the notion that the psychotropic
      effects of agomelatine are due to the synergy between its melatonergic and 5
      hydroxytryptaminergic effects. The recent demonstration of the existence of
      heteromeric complexes of MT1 and MT2 with 5-HT2C receptors at the cellular level
      may explain how these two properties of agomelatine translate into a synergistic
      action that, for example, leads to increases in hippocampal proliferation,
      maturation and survival through modulation of multiple cellular pathways
      (increase in trophic factors, synaptic remodelling, glutamate signalling) and key
      targets (early genes, kinases). The present review focuses on the pharmacological
      properties of this novel antidepressant. Its mechanism of action, strikingly
      different from that of conventional classes of antidepressants, opens
      perspectives towards a better understanding of the physiopathological bases
      underlying depression. 

PMID- 24724694
TI  - Comparison of experimental fine-mapping to in silico prediction results of HIV-1
      epitopes reveals ongoing need for mapping experiments.
AB  - Methods for identifying physiologically relevant CD8 T-cell epitopes are
      critically important not only for the development of T-cell-based vaccines but
      also for understanding host-pathogen interactions. As experimentally mapping an
      optimal CD8 T-cell epitope is a tedious procedure, many bioinformatic tools have
      been developed that predict which peptides bind to a given MHC molecule. We
      assessed the ability of the CD8 T-cell epitope prediction tools syfpeithi,
      ctlpred and iedb to foretell nine experimentally mapped optimal HIV-specific
      epitopes. Randomly - for any of the subjects' HLA type and with any matching
      score - the optimal epitope was predicted in seven of nine epitopes using
      syfpeithi, in three of nine epitopes using ctlpred and in all nine of nine
      epitopes using iedb. The optimal epitope within the three highest ranks was given
      in four of nine epitopes applying syfpeithi, in two of nine epitopes applying
      ctlpred and in seven of nine epitopes applying iedb when screening for all of the
      subjects' HLA types. Knowing the HLA restriction of the peptide of interest
      improved the ranking of the optimal epitope within the predicted results.
      Epitopes restricted by common HLA alleles were more likely to be predicted than
      those restricted by uncommon HLA alleles. Epitopes with aberrant lengths compared
      with the usual HLA-class I nonamers were most likely not predicted. Application
      of epitope prediction tools together with literature searches for already
      described optimal epitopes narrows down the possibilities of optimal epitopes
      within a screening peptide of interest. However, in our opinion, the actual fine
      mapping of a CD8 T-cell epitope cannot yet be replaced.

PMID- 24724701
TI  - The Arabidopsis STRESS RESPONSE SUPPRESSOR DEAD-box RNA helicases are nucleolar-
      and chromocenter-localized proteins that undergo stress-mediated relocalization
      and are involved in epigenetic gene silencing.
AB  - DEAD-box RNA helicases are involved in many aspects of RNA metabolism and in
      diverse biological processes in plants. Arabidopsis thaliana mutants of two DEAD
      box RNA helicases, STRESS RESPONSE SUPPRESSOR1 (STRS1) and STRS2 were previously
      shown to exhibit tolerance to abiotic stresses and up-regulated stress-responsive
      gene expression. Here, we show that Arabidopsis STRS-overexpressing lines
      displayed a less tolerant phenotype and reduced expression of stress-induced
      genes confirming the STRSs as attenuators of Arabidopsis stress responses. GFP
      STRS fusion proteins exhibited localization to the nucleolus, nucleoplasm and
      chromocenters and exhibited relocalization in response to abscisic acid (ABA)
      treatment and various stresses. This relocalization was reversed when stress
      treatments were removed. The STRS proteins displayed mis-localization in specific
      gene-silencing mutants and exhibited RNA-dependent ATPase and RNA-unwinding
      activities. In particular, STRS2 showed mis-localization in three out of four
      mutants of the RNA-directed DNA methylation (RdDM) pathway while STRS1 was mis
      localized in the hd2c mutant that is defective in histone deacetylase activity.
      Furthermore, heterochromatic RdDM target loci displayed reduced DNA methylation
      and increased expression in the strs mutants. Taken together, our findings
      suggest that the STRS proteins are involved in epigenetic silencing of gene
      expression to bring about suppression of the Arabidopsis stress response. 

PMID- 24724702
TI  - Monofluoroacetate-containing plants that are potentially toxic to livestock.
AB  - Many plants worldwide contain monofluoroacetate and cause sudden death in
      livestock. These plants are primarily found in the southern continents of Africa,
      Australia, and South America, where they negatively affect livestock production.
      This review highlights past and current research investigating (1) the plants
      reported to contain monofluoroacetate and cause sudden death; (2) the mode of
      action, clinical signs, and pathology associated with poisoning by
      monofluoroacetate-containing plants; (3) chemical methods for the analysis of
      monofluoroacetate in plants; (4) the coevolution of native flora and fauna in
      Western Australia with respect to monofluoroacetate-containing plants; and (5)
      methods to mitigate livestock losses caused by monofluoroacetate-containing
      plants. 

PMID- 24724703
TI  - Sarcoidosis presenting as scleral nodule.

PMID- 24724704
TI  - Letter to the editor.

PMID- 24724705
TI  - Letter to the editor: author response.

PMID- 24724706
TI  - A convergent synthetic platform for single-nanoparticle combination cancer
      therapy: ratiometric loading and controlled release of cisplatin, doxorubicin,
      and camptothecin.
AB  - The synthesis of polymer therapeutics capable of controlled loading and
      synchronized release of multiple therapeutic agents remains a formidable
      challenge in drug delivery and synthetic polymer chemistry. Herein, we report the
      synthesis of polymer nanoparticles (NPs) that carry precise molar ratios of
      doxorubicin, camptothecin, and cisplatin. To our knowledge, this work provides
      the first example of orthogonally triggered release of three drugs from single
      NPs. The highly convergent synthetic approach opens the door to new NP-based
      combination therapies for cancer. 

PMID- 24724707
TI  - Effect of solution and solid-phase conditions on the Fe(II)-accelerated
      transformation of ferrihydrite to lepidocrocite and goethite.
AB  - Aqueous ferrous iron (Fe(II)) accelerates the transformation of ferrihydrite into
      secondary, more crystalline minerals however the factors controlling the rate
      and, indeed, the underlying mechanism of this transformation process remain
      unclear. Here, we present the first detailed study of the kinetics of the Fe(II)
      accelerated transformation of ferrihydrite to goethite, via lepidocrocite, for a
      range of pH and Fe(II) concentrations and, from the results obtained, provide
      insight into the factors controlling the transformation rate and the processes
      responsible for transformation. A reaction scheme for the Fe(II)-accelerated
      secondary mineralization of ferrihydrite is developed in which an Fe(II) atom
      attaches to the ferrihydrite surface where it is immediately oxidized to Fe(III)
      with the resultant electron transferred, sequentially, to other iron oxyhydroxide
      Fe(III) atoms before release to solution as Fe(II). This freshly precipitated
      Fe(III) forms the nuclei for the formation of secondary minerals and also
      facilitates the ongoing uptake of Fe(II) from solution by creation of fresh
      surface sites. The concentration of solid-associated Fe(II) and the rate of
      transport of Fe(II) to the oxyhydroxide surface appear to determine which
      particular secondary minerals form and their rates of formation. Lepidocrocite
      growth is enhanced at lower solid-associated Fe(II) concentrations while
      conditions leading to more rapid uptake of Fe(II) from solution lead to higher
      goethite growth rates. 

PMID- 24724708
TI  - Differential bradykinin B1 and B2 receptor regulation in cell death induced by
      hepatic ischaemia/reperfusion injury.
AB  - The biological and pharmacological effects of BK (bradykinin) are mediated by two
      receptors: the constitutive B2R (B2 receptor) and the inducible B1R (B1
      receptor). BK plays a role in the hepatic microcirculation by inducing the PHR
      (portal hypertensive response) via B2R, whereas DABK (des-Arg9-BK), a B1R
      agonist, does not elicit the response. During IRI (ischaemia/reperfusion injury),
      important changes occur in the microcirculation, and cell death by necrosis and
      apoptosis is involved in poor graft function. The aim of the present study was to
      analyse the role of B1R and B2R in liver cell death induced by IRI. Livers from
      Wistar rats were submitted to ischaemia (4 degrees C) for 4 or 24 h. After this
      period, livers were reperfused ex vivo with Krebs-Henseleit solution (37 degrees
      C). BK or DABK was then injected as a bolus during reperfusion in the absence or
      presence of HOE-140 (a B2R antagonist) or DALBK (des-Arg(9)-Leu(8)-BK) (a B1R
      antagonist) respectively. Liver viability was analysed by glucose release and
      bile secretion. The PHR to kinins did not change. Cell death was higher in the
      DABK group and its antagonist significantly decreased cell death. Interestingly,
      the B1R antagonist did not alter the number of necrotic cells, but it decreased
      the number of apoptotic cells. On the other hand, the B2R antagonist decreased
      the number of necrotic cells, but did not alter the number of apoptotic cells.
      Therefore B1R may participate in apoptotic cell death signalling, and B2R may be
      involved in necrotic cell death.

PMID- 24724710
TI  - Hypothesis-Based Weight of Evidence: An Approach to Assessing Causation and its
      Application to Regulatory Toxicology.
AB  - Other papers in this symposium focus on combining direct observations or
      measurements of a phenomenon of interest. Here, I consider the distinct problem
      of integrating diverse kinds of data to address the scientific case for
      toxicological causation in view of information that usually contains gaps and
      outright contradictions. Existing weight-of-evidence approaches have been
      criticized as either too formulaic or too vague, simply calling for professional
      judgment that is hard to trace to its scientific basis. I discuss an approach
      hypothesis-based weight of evidence-that emphasizes articulation of the
      hypothesized generalizations, their basis, and span of applicability.
      Hypothesized common processes should be expected to act elsewhere as well-in
      different species or different tissues-and so outcomes that ought to be affected
      become part of the evidence evaluation. A compelling hypothesis is one that
      provides a common unified explanation for observed results. Any apparent
      exceptions and failures to account for some data must be plausibly explained. Ad
      hoc additions to the explanations introduced to "save" hypotheses from apparent
      contradiction weaken the degree to which available data test causal propositions.
      In the end, we need an "account" of all the results at hand, specifying what is
      ascribed to hypothesized common causal processes and what to special exceptions,
      chance, or other factors. Evidence is weighed by considering comparative
      plausibility of an account including the proposed causal effect versus an
      alternative that explains all of the results at hand otherwise. 

PMID- 24724711
TI  - pH-sensitive tubular polymersomes: formation and applications in cellular
      delivery.
AB  - Optimizing the shape of a nanovector influences its interaction with a cell and
      determines the internalization kinetics. Block copolymer amphiphiles self
      assemble into monodisperse structures in aqueous solutions and have been explored
      extensively as drug delivery vectors. However, the structure of self-assembled
      block copolymers has mainly been limited to spherical vesicles or spherical and
      worm-like micelles. Here we show the controlled formation and purification of
      tubular polymersomes, long cylindrical vesicles. Tubular polymersomes are
      purified from other structures, and their formation is manipulated by
      incorporating the biocompatible membrane components cholesterol and
      phospholipids. Finally we show that these tubular polymersomes have different
      cellular internalization kinetics compared with spherical polymersomes and can
      successfully encapsulate and deliver fluorescent bovine serum albumin protein
      intracellularly. 

PMID- 24724712
TI  - The analyst's anxieties in the first interview: barriers against analytic
      presence.
AB  - To answer the questions: why don't more people enter analysis and how do we get
      more people to do so? Attention is drawn to anxieties in the analyst that become
      obstacles to the initiation of analysis. The main focus of the paper is how to
      understand why analysts, irrespective of patient characteristics, seem to have
      resistances against embarking on analysis. Being a meeting between strangers the
      consultation activates strong emotional reactions in both parties. One way of
      coping is defensively to diagnose, assess and exclude instead of being present as
      an analyst. The analytic frame of a consultation is ambiguous, and a secure
      analytic function is needed in order to meet the openness and unpredictability of
      this frame. A fragile psychoanalytic identity is seen as central to analysts'
      failure to create an analytic practice; it takes years to develop and maintain a
      robust analytic function, and analytic work continues to cause disturbing
      emotional reactions in the analyst. Analysts' vulnerable identity is also linked
      to the history of psychoanalysis that has fostered an ideal of analytic practice
      that is omnipotent and impossible to reach. Therefore it is no wonder that
      attempts to reach a convinced recommendation of analysis can become diverted in
      the process of consultation. Confronting these inner impediments in order to
      strengthen the analytic identity is suggested as a better way to get more
      analytic patients than to keep looking for so-called analysability in patients. 

PMID- 24724713
TI  - Effectiveness of female community health volunteers in the detection and
      management of low-birth-weight in Nepal.
AB  - INTRODCTION: Low birth weight (LBW) is a major risk factor for neonatal death.
      However, most neonates in low-income countries are not weighed at birth. This
      results in many LBW infants being overlooked. Female community health volunteers
      (FCHVs) in Nepal are non-health professionals who are living in local communities
      and have already worked in a field of reproductive and child health under the
      government of Nepal for more than 20 years. The effectiveness of involving FCHVs
      to detect LBW infants and to initiate prompt action for their care was studied in
      rural areas of Nepal. METHODS: FCHVs were tasked with weighing all neonates born
      in selected areas using color-coded spring scales. Supervisors repeated each
      weighing using electronic scales as the gold standard comparator. Data on the
      relative birth sizes of the infants, as assessed by their mothers, were also
      collected and compared with the measured weights. Each of the 205 FCHVs involved
      in the study was asked about the steps that she would take when she came across a
      LBW infant, and knowledge of zeroing a spring scale was also assessed through
      individual interviews. The effect of the background social characteristics of the
      FCHVs on their performance was examined by logistic regression. This study was
      nested within a community-based neonatal sepsis-management intervention
      surveillance system, which facilitated an assessment of the performance of the
      FCHVs in weighing neonates, coverage of FCHVs' visits, and weighing of babies
      through maternal interviews. RESULTS: A total of 462 babies were weighed, using
      both spring scales and electronic scales, within 72 hours of birth. The
      prevalence of LBW, as assessed by the gold standard method, was 28%. The
      sensitivity of detection of LBW by FCHVs was 89%, whereas the sensitivity of the
      mothers' perception of size at birth was only 40%. Of the 205 FCHVs participating
      in the study, 70% of FCHVs understood what they should do when they identified
      LBW and very low birth weight (VLBW) infants. Ninety-six per cent could describe
      how to zero a scale and approximately 50% could do it correctly. Seventy-seven
      per cent of FCHVs weighed infants at least once during the study period, and 19
      of them (12%) miscategorized infant weights. Differences were not detected
      between the background social characteristics of FCHVs who miscategorized infants
      and those who did not. On the basis of maternal reporting, 67% of FCHVs who
      visited infants had weighed them. CONCLUSIONS: FCHVs are able to correctly
      identify LBW and VLBW infants using spring scales and describe the correct steps
      to take after identification of these infants. Use of FCHVs as newborn care
      providers allows for utilization of their logistical, geographical, and cultural
      strengths, particularly a high level of access to neonates, that can complement
      the Nepalese healthcare system. Providing additional training to and increasing
      supervision of local FCHVs regarding birth weight measurement will increase the
      identification of high-risk neonates in resource-limited settings.

PMID- 24724714
TI  - Clinical course of vestibular schwannoma in pediatric neurofibromatosis Type 2.
AB  - OBJECT: Neurofibromatosis Type 2 (NF2) is an autosomal-dominant inherited
      disease, characterized by multiple neoplasia syndromes, including meningioma,
      schwannoma, glioma, and ependymoma. In this report, the authors present their
      clinical experience with pediatric NF2 patients. In particular, they focused on
      the clinical course of vestibular schwannoma (VS), including the natural growth
      rate, tumor control, and functional hearing outcomes. METHODS: From May 1988 to
      June 2012, the authors recruited patients who were younger than 18 years and
      fulfilled the Manchester criteria. In total, 25 patients were enrolled in this
      study. The authors analyzed the clinical course of these patients. In addition,
      they measured the natural growth rate of VS before any treatment in these
      children with NF2. Then, they evaluated the tumor control rate and functional
      hearing outcomes after the treatment of VS. RESULTS: The mean age at the onset of
      NF2-related symptoms was 9.9 +/- 4.5 years (mean +/- SD, range 1-17 years). The
      mean age at the diagnosis of NF2 was 12.9 +/- 2.9 years (range 5-17 years). The
      mean follow-up period was 89.3 months (range 12-311 months). As initial
      manifestations, nonvestibular symptoms were frequently observed in pediatric
      patients with NF2. The mean natural growth rate of VS was 0.33 +/- 0.41
      cm(3)/year (range 0-1.35 cm(3)/year). The tumor control rate of VS was 35.3% at 3
      years after Gamma Knife surgery (GKS). The actuarial rate of useful hearing
      preservation was 67% in the 1st year and 53% in the 5th year after GKS.
      CONCLUSIONS: Clinical manifestations in children with NF2 were highly variable,
      compared with their adult counterparts. The natural growth rate of VS in children
      is slow, and this oncological feature may explain the diverse clinical
      manifestations besides vestibular symptoms in children with NF2. The treatment
      outcome of GKS for VS in children with NF2 was not favorable compared with
      previous reports of affected adults.

PMID- 24724715
TI  - External validation of the Chicago Chiari Outcome Scale.
AB  - OBJECT: Historically, assessment of clinical outcomes following surgical
      management of Chiari malformation Type I (CM-I) has been challenging due to the
      lack of a validated instrument for widespread use. The Chicago Chiari Outcome
      Scale (CCOS) is a novel system intended to provide a less subjective evaluation
      of outcomes for patients with CM-I. The goal of this study was to externally
      validate the performance of the CCOS. METHODS: Patients undergoing surgery for CM
      I between 2001 and 2012 were reviewed (n = 292). Inclusion criteria for this
      study were as follows: 1) patients receiving primary posterior fossa
      decompression; 2) at least 5.5 months of postoperative clinical follow-up; and 3)
      patients <= 18 years of age at the time of surgery. Outcomes were evaluated using
      the CCOS, along with a "gestalt" impression of whether patients experienced
      significant improvement after surgery. A subgroup of 118 consecutive patients
      undergoing operations between 2008 and 2010 was selected for analysis of
      interrater reliability (n = 73 meeting inclusion/exclusion criteria). In this
      subgroup, gestalt and CCOS scores were independently determined by 2 reviewers,
      and interrater reliability was assessed using the intraclass correlation
      coefficient (ICC) and kappa (kappa) statistic. RESULTS: The median CCOS score was
      14, and 67% of patients had improved gestalt scores after surgery. Overall, the
      CCOS was effective at identifying patients with improved outcome after surgery
      (area under curve = 0.951). The interrater reliability of the CCOS (ICC = 0.71)
      was high, although the reliability of the component scores ranged from poor to
      good (ICC 0.23-0.89). The functionality subscore demonstrated a low ICC and did
      not add to the predictive ability of the logistic regression model (likelihood
      ratio = 1.8, p = 0.18). When analyzing gestalt outcome, there was moderate
      agreement between raters (kappa = 0.56). CONCLUSIONS: In this external validation
      study, the CCOS was effective at identifying patients with improved outcomes and
      proved more reliable than the authors' gestalt impression of outcome. However,
      certain component subscores (functionality and nonpain symptoms) were found to be
      less reliable, and may benefit from further definition in score assignment. In
      particular, the functionality subscore does not add to the predictive ability of
      the CCOS, and may be unnecessary. Overall, the authors found the CCOS to be an
      improvement over the previously used assessment of outcome at their institution.

PMID- 24724716
TI  - Results of a North American survey of rapid-sequence MRI utilization to evaluate
      cerebral ventricles in children.
AB  - OBJECT: Growing concern about potential adverse effects of ionizing radiation
      exposure during imaging studies is particularly relevant to the pediatric
      population. To decrease radiation exposure, many institutions use rapid-sequence
      (or quick-brain) MRI to evaluate cerebral ventricle size. There are obstacles,
      however, to widespread implementation of this imaging modality. The purpose of
      this study was to define and quantify these obstacles to positively affect
      institutional and governmental policy. METHODS: A 9-question survey was emailed
      to pediatric neurosurgeons who were either members or candidate members of the
      American Society of Pediatric Neurosurgeons at every one of 101 institutions in
      the US and Canada having such a neurosurgeon on staff. Responses were compiled
      and descriptive statistics were performed. RESULTS: Fifty-six institutions
      completed the survey. Forty-four (79%) of the 56 institutions currently have a
      rapid-sequence MRI protocol to evaluate ventricle size, while 36 (64%) use it
      routinely. Of the 44 institutions with a rapid-sequence MRI protocol, 29 (66%)
      have had a rapid-sequence MRI protocol for less than 5 years while 39 (89%) have
      had a rapid-sequence MRI protocol for no more than 10 years. Thirty-six (88%) of
      41 rapid-sequence MRI users responding to this question obtain a T2-weighted
      rapid-sequence MRI while 13 (32%) obtain a T1-weighted rapid-sequence MRI. Twenty
      eight (64%) of 44 institutions never use sedation while an additional 12 (27%)
      rarely use sedation to obtain a rapid-sequence MRI (less than 5% of studies). Of
      the institutions with an established rapid-sequence MRI protocol, obstacles to
      routine use include lack of emergency access to MRI facilities in 18 (41%), lack
      of staffing of MRI facilities in 12 (27%), and the inability to reimburse a rapid
      sequence MRI protocol in 6 (14%). In the 12 institutions without rapid-sequence
      MRI, obstacles to implementation include lack of emergency access to MRI
      facilities in 8 (67%), lack of staffing of MRI facilities in 7 (58%), the
      inability to reimburse in 3 (25%), and lack of administrative support in 3 (25%).
      To evaluate pediatric head trauma, 53 (96%) of 55 institutions responding to this
      question use noncontrast CT, no institution uses rapid-sequence MRI, and only 2
      (4%) use standard MRI. CONCLUSIONS: Many North American institutions have a rapid
      sequence MRI protocol to evaluate ventricle size, with most developing this
      technique within the past 5 years. Most institutions never use sedation, and most
      obtain T2-weighted sequences. The greatest obstacles to the routine use of rapid
      sequence MRI in institutions with and in those without a rapid-sequence MRI
      protocol are the lack of emergency access and staffing of the MRI facility during
      nights and weekends.

PMID- 24724717
TI  - Ependymoblastoma with cystic change in a child.
AB  - Ependymoblastoma is a rare and devastating primitive neuroectodermal tumor with
      ependymal differentiation. This tumor occurs very early in life and shows rapid
      growth and a diffuse infiltration through the leptomeningeal space. This neoplasm
      is characterized by uniform neuroepithelial cells, multilayered ependymal
      rosettes, perivascular pseudorosettes, and numerous mitotic figures. In this
      article, the authors report on a 4-year-old girl who was diagnosed as having an
      ependymoblastoma with cystic change. After a series of laboratory and imaging
      examinations, the left frontal solid-cystic lesion was surgically excised.
      Histological examinations confirmed the diagnosis of ependymoblastoma. The
      patient's intracranial hypertension symptoms were alleviated, and postoperative
      chemotherapy was performed. At the 6-month follow-up visit, MRI demonstrated
      evidence of relapse, and the girl died of tumor recurrence 14 months after
      surgery. Databases (PubMed, MEDLINE, Embase, and Web of Science) were searched
      for relevant articles published from 1970 to 2012; 71 eligible cases of
      ependymoblastoma were obtained, and 42 provided complete clinical details.
      Prognosis of children with ependymoblastoma is poor, and data on clinical
      behavior and optimal treatment strategies are lacking, but sustained remissions
      have been achieved after multimodal treatment according to existing literature.
      In this report, the clinical and histopathological features and therapeutic
      options of this tumor are discussed in the light of the published data. Further
      studies, especially those examining multimodality therapy, are needed to improve
      survival of children with this rare malignant CNS tumor. 

PMID- 24724718
TI  - Contribution of copy number variations in CMT1X: a retrospective study.
AB  - BACKGROUND AND PURPOSE: Charcot-Marie-Tooth disease type 1X (CMT1X) is an X
      linked dominant hereditary motor-sensory peripheral neuropathy, which results
      from mutations in the Gap Junction B1 (GJB1) gene. In a few cases, gene deletions
      have been linked to the disease, but their relative contribution in the
      pathogenesis of CMT1X has not been assessed yet. Herein a retrospective study to
      establish the incidence of gene deletions is described. METHODS: Copy number
      variation analysis was performed by multiplex ligation-dependent probe
      amplification, whilst the breakpoints were defined by Sanger sequencing. RESULTS:
      A novel GJB1 deletion was identified in a family presenting with a classical
      CMT1X phenotype. The rearrangement includes the coding and the regulatory regions
      of GJB1. CONCLUSIONS: GJB1 deletions appear to be a rare but not insignificant
      cause of CMT1X and are associated with a typical disease phenotype. Accordingly,
      patients negative for point mutations whose pedigree and clinical records
      strongly suggest the possibility of CMT1X should be tested for GJB1 copy number
      variations.

PMID- 24724720
TI  - Reversible paralysis and loss of deep pain sensation after topical intrathecal
      morphine administration following durotomy.
AB  - OBJECTIVE: To report 2 dogs that developed temporary pelvic limb paralysis with
      loss of deep pain sensation after topical intrathecal morphine administration
      during spinal surgery. STUDY DESIGN: Clinical report. ANIMALS: Dogs (n = 2).
      METHODS: A 5-year-old castrated male French Bulldog with a subarachnoid
      diverticulum at T9-T10 and a 9.5-year-old castrated male Belgian Shepherd dog
      with a herniated disc at T12-T13 and intradural component, had Gelfoam soaked
      with morphine placed over the dura mater defect. RESULTS: Pelvic limb paralysis
      and loss of deep pain sensation was noticed immediately after recovery from
      anesthesia. After intravenous naloxone administration, both dogs immediately
      regained ambulation and normal pain sensation; however the effect was temporary
      lasting only a few hours. Permanent resolution of clinical signs occurred 24
      hours after surgery. CONCLUSIONS: Topical intrathecal morphine administration
      resulted in temporary pelvic limb paralysis and loss of deep pain sensation. This
      route of administration should be used cautiously until further determination of
      the efficacy and adverse effects associated with topical intrathecal morphine
      administration.

PMID- 24724719
TI  - Cabozantinib-induced thyroid dysfunction: a review of two ongoing trials for
      metastatic bladder cancer and sarcoma.
AB  - BACKGROUND: Thyroid dysfunction is a common adverse event associated with
      tyrosine kinase inhibitors (TKI), but its underlying pathophysiology is unclear.
      Cabozantinib is a novel TKI currently Food and Drug Administration approved for
      advanced medullary thyroid cancer and tested in clinical trials on solid tumors
      including prostate, liver, bladder, breast, and ovarian cancer. METHODS: We
      analyzed the thyroid function of patients enrolled in two phase 2 clinical trials
      using cabozantinib at the National Institutes of Health Clinical Center. Two
      cases of thyroiditis associated with cabozantinib therapy are presented in
      detail, and a systematic review of the literature on TKI-associated thyroid
      dysfunction is also discussed. RESULTS: Between September 2012 and September
      2013, 33 patients were treated with cabozantinib, and follow-up thyroid function
      tests were available for 31 (20 males, 11 females; age 59+/-1 years). Thyroid
      dysfunction was recorded in the majority of patients (93.1%), with a predominance
      of subclinical hypothyroidism. Two cases showed a biphasic pattern of thyroid
      dysfunction characterized by a transient thyrotoxicosis followed by
      hypothyroidism. Color Doppler demonstrated an increase in vascularization during
      the thyrotoxic phase, but no uptake was visualized on nuclear medicine imaging. A
      systematic review of the literature resulted in the identification of 40 original
      manuscripts, of which 13 were case series and 6 were case reports describing TKI
      associated thyroid dysfunction. CONCLUSION: TKI therapy often results in
      clinically significant thyroid dysfunction. Cabozantinib treatment commonly
      results in thyroid dysfunction varying from subclinical hypothyroidism to
      symptomatic thyrotoxicosis. Early detection and characterization of cabozantinib
      associated thyroid dysfunction and close follow-up are essential to provide
      adequate management of this common adverse event.

PMID- 24724721
TI  - Cadmium exposure affects iron acquisition in barley (Hordeum vulgare) seedlings.
AB  - This study addresses the question of the interference between iron (Fe) nutrition
      and cadmium (Cd) toxicity at the level of growth performance, phytosiderophores
      (PS) release, micronutrient accumulation and expression of genes involved in Fe
      homeostasis in barley seedlings, a plant with strategy II-based response to Fe
      shortage. Cd exposure induced responses similar to those of genuine Fe deficiency
      also in Fe-sufficient plants. Most genes involved in PS biosynthesis and
      secretion (HvNAS3, HvNAS4, HvNAS6, HvNAS7, HvNAAT-A, HvDMAS1 and HvTOM1) induced
      by Fe deprivation were also significantly upregulated in the presence of Cd under
      Fe sufficient conditions. Accordingly, the enhanced expression of these genes in
      roots under Cd exposure was accompanied by an increase of PS release. However,
      induced expression of HvIRO2 and the downregulation of HvIDEF1 and HvIRT1, after
      Cd exposure, suggested the presence of a pathway that induces HvIRO2-mediated PS
      biosynthesis under Cd stress, which probably is not simply caused by Fe
      deficiency. The downregulation of HvIRT1 and HvNramp5 may represent a protective
      mechanism at transcriptional level against further Cd uptake by these
      transporters. These results likely indicate that Cd itself may be able to
      activate Fe acquisition mechanism in an Fe-independent manner. 

PMID- 24724722
TI  - CuBr-promoted formal hydroacylation of 1-alkynes with glyoxal derivatives: an
      unexpected synthesis of 1,2-dicarbonyl-3-enes.
AB  - An efficient and concise protocol has been developed for the highly regio- and
      stereoselective synthesis of E-1,2-dicarbonyl-3-ene derivatives by a copper
      promoted reaction of 1-alkynes with alpha-carbonyl aldehydes in the presence of
      morpholine. The products obtained are believed as the formal hydroacylation of
      the triple bond. 

PMID- 24724723
TI  - Melatonin receptor type 1 signals to extracellular signal-regulated kinase 1 and
      2 via Gi and Gs dually coupled pathways in HEK-293 cells.
AB  - The pineal gland hormone melatonin exerts its regulatory roles in a variety of
      physiological and pathological responses through two G protein-coupled receptors,
      melatonin receptor type 1 (MT1) and melatonin receptor type 2 (MT2), which have
      been recognized as promising targets in the treatment of a number of human
      diseases and disorders. The MT1 receptor was identified nearly 20 years ago;
      however, the molecular mechanisms by which MT1-mediated signaling affects
      physiology remain to be further elucidated. In this study, using HEK293 cells
      stably expressing the human MT1 receptor, melatonin induced a concentration
      dependent activation of extracellular signal-regulated kinase 1 and 2 (ERK1/2).
      The melatonin-mediated phosphorylation of ERK1/2 at later time points (>=5 min)
      was strongly suppressed by pretreatment with pertussis toxin, but only a slight,
      if any, inhibition of ERK1/2 activation at early time points (<=2 min) was
      detected. Further experiments demonstrated that the Gbetagamma subunit,
      phosphoinositide 3-kinase, and calcium-insensitive protein kinase C were involved
      in the MT1-mediated activation of ERK1/2 at later time points (>=5 min).
      Moreover, results derived from cAMP assays combined with a MT1 mutant indicated
      that the human MT1 receptor could also couple to Gs protein, stimulating
      intracellular cAMP formation, and that the MT1-induced activation of ERK1/2 at
      early time points (<=2 min) was mediated by the Gs/cAMP/PKA cascade. Our findings
      may provide new insights into the pharmacological effects and physiological
      functions modulated by the MT1-mediated activation of ERK1/2. 

PMID- 24724724
TI  - Fluoroscopy of spontaneous breathing is more sensitive than phrenic nerve
      stimulation for detection of right phrenic nerve injury during cryoballoon
      ablation of atrial fibrillation.
AB  - INTRODUCTION: Right phrenic nerve palsy (PNP) is a typical complication of
      cryoballoon ablation of the right-sided pulmonary veins (PVs). Phrenic nerve
      function can be monitored by palpating the abdomen during phrenic nerve pacing
      from the superior vena cava (SVC pacing) or by fluoroscopy of spontaneous
      breathing. We sought to compare the sensitivity of these 2 techniques during
      cryoballoon ablation for detection of PNP. METHODS AND RESULTS: A total of 133
      patients undergoing cryoballoon ablation were monitored with both SVC pacing and
      fluoroscopy of spontaneous breathing during ablation of the right superior PV.
      PNP occurred in 27/133 patients (20.0%). Most patients (89%) had spontaneous
      recovery of phrenic nerve function at the end of the procedure or on the
      following day. Three patients were discharged with persistent PNP. All PNP were
      detected first by fluoroscopic observation of diaphragm movement during
      spontaneous breathing, while diaphragm could still be stimulated by SVC pacing.
      In patients with no recovery until discharge, PNP occurred at a significantly
      earlier time (86 +/- 34 seconds vs. 296 +/- 159 seconds, P < 0.001). No recovery
      occurred in 2/4 patients who were ablated with a 23 mm cryoballoon as opposed to
      1/23 patients with a 28 mm cryoballoon (P = 0.049). CONCLUSION: Fluoroscopic
      assessment of diaphragm movement during spontaneous breathing is more sensitive
      for detection PNP as compared to SVC pacing. PNP as assessed by fluoroscopy is
      frequent (20.0%) and carries a high rate of recovery (89%) until discharge. Early
      onset of PNP and use of 23 mm cryoballoon are associated with PNP persisting
      beyond hospital discharge.

PMID- 24724728
TI  - The relative importance of patients' decisional control preferences and
      experiences.
AB  - OBJECTIVE: Patients' role in treatment decision-making can influence psychosocial
      and health-related outcomes (i.e. satisfaction, felt respect, adherence). We
      examined decisional control in a surgical context, identifying correlates of
      patients' preferences and experiences. DESIGN: 380 patients and 7 surgeons were
      surveyed during initial surgical consultation visits in a low-income outpatient
      clinic. MEASURES: Patients reported preferences for (pre-consultation) and
      experiences of (post-consultation) decisional control, demographics, satisfaction
      with care, and adherence to treatment recommendations. Surgeons rated patients'
      health status. RESULTS: Preferences for and experiences of decisional control
      were unrelated, suggesting significant preference-experience misalignment.
      However, this misalignment did not appear to be consequential for patient
      outcomes. Rather, more decisional control, regardless of patients' preferences,
      predicted greater satisfaction with care and greater self-reported adherence as
      assessed at a post-surgical appointment. CONCLUSIONS: Decisional control predicts
      better outcomes for patients, regardless of their preferences for control over
      treatment decisions. These findings suggest that interventions should aim to
      increase patients' degree of decisional control when feasible and appropriate.

PMID- 24724729
TI  - Influence of systemic corticotherapy on the triggering of pityriasis versicolor.
AB  - Pityriasis versicolor is a frequent mycosis and the use of systemic
      corticotherapy is one of its predisposing factors. This is an observational,
      cross-sectional, analytical and comparative study, conducted from January 2012 to
      January 2013 in the following outpatient clinics: Dermatology Service, Cassiano
      Antonio Moraes Hospital (HUCAM), Vitoria, ES, Brazil; Nephrology Service, HUCAM;
      and Leprosy Department, Maruipe Health Unit, Vitoria, ES, Brazil. Patients,
      undergoing long-term systemic corticotherapy (or not), were assessed with respect
      to the presence of pityriasis versicolor. If there was mycosis, a direct
      mycological examination would be carried out. The spss 17.0 software was used for
      the statistical analysis. From the total of 100 patients, nine had pityriasis
      versicolor, being eight from the corticotherapy group and one from the group with
      no use of corticosteroids. Regarding the patients with mycosis, the prevalent age
      ranged from 20 to 39 years, with six patients; six were women; seven mixed race;
      eight were undergoing long-term systemic corticotherapy; seven were taking low
      dose systemic corticosteroids; four had leucocytosis; five had normal total
      cholesterol and triglycerides; and four had normal glycaemia. There was increased
      frequency of pityriasis versicolor in the group undergoing systemic
      corticotherapy with statistical significance, corroborating the only study on the
      topic (1962).

PMID- 24724730
TI  - Enhanced biocontrol activity of Rhodotorula mucilaginosa cultured in media
      containing chitosan against postharvest diseases in strawberries: possible
      mechanisms underlying the effect.
AB  - The effect of Rhodotorula mucilaginosa cultured in media containing chitosan on
      its antogonistic activity against postharvest diseases of strawberries and the
      possible mechanisms involved are discussed. Two-dimensional gel electrophoresis
      were applied in the analysis of the proteins of R. mucilaginosa in response to
      chitosan. Compared with the application of R. mucilaginosa alone, the biocontrol
      efficacy of the yeast combined with 0.5% chitosan was enhanced greatly, with
      significant increase in chitinase activity of antagonistic yeast,
      polyphenoloxidase, peroxidase, phenylalanine ammonia lyase, chitinase and beta
      1,3-glucanase activity, and with an inhibition of lipid peroxidation of
      strawberries. The population of R. mucilaginosa harvested from NYDB amended with
      chitosan at 0.5% increased rapidly in strawberry wounds compared with those
      harvested from NYDB without chitosan. In the cellular proteome, several
      differentially expressed proteins were identified, most of which were related to
      basic metabolism. 

PMID- 24724725
TI  - TRP channels and STIM/ORAI proteins: sensors and effectors of cancer and stroma
      cell migration.
AB  - Cancer cells are strongly influenced by host cells within the tumour stroma and
      vice versa. This leads to the development of a tumour microenvironment with
      distinct physical and chemical properties that are permissive for tumour
      progression. The ability to migrate plays a central role in this mutual
      interaction. Migration of cancer cells is considered as a prerequisite for tumour
      metastasis and the migration of host stromal cells is required for reaching the
      tumour site. Increasing evidence suggests that transient receptor potential (TRP)
      channels and STIM/ORAI proteins affect key calcium-dependent mechanisms
      implicated in both cancer and stroma cell migration. These include, among others,
      cytoskeletal remodelling, growth factor/cytokine signalling and production, and
      adaptation to tumour microenvironmental properties such as hypoxia and oxidative
      stress. In this review, we will summarize the current knowledge regarding TRP
      channels and STIM/ORAI proteins in cancer and stroma cell migration. We focus on
      how TRP channel or STIM/ORAI-mediated Ca(2+) signalling directly or indirectly
      influences cancer and stroma cell migration by affecting the above listed
      mechanisms. LINKED ARTICLES: This article is part of a themed section on
      Cytoskeleton, Extracellular Matrix, Cell Migration, Wound Healing and Related
      Topics. To view the other articles in this section visit
      http://dx.doi.org/10.1111/bph.2014.171.issue-24.

PMID- 24724731
TI  - Predictors of anonymous cyber aggression: the role of adolescents' beliefs about
      anonymity, aggression, and the permanency of digital content.
AB  - Little attention has been given to whether adolescents' beliefs about anonymity
      and their normative beliefs about cyber aggression jointly increase their
      perpetration of cyber aggression. To this end, the present longitudinal study
      examined the moderating influence of these variables on the relationships among
      adolescents' attitudes toward the permanency of digital content, confidence with
      not getting caught, and anonymous cyber aggression (ACA) assessed 1 year later
      (Time 2). These associations were examined among 274 7th and 8th graders and
      through five technologies, including social networking sites (SNS), e-mail,
      instant messenger (IM), mobile phones, and chatrooms. Findings indicated that
      increases in Time 2 ACA and attitudes toward the permanency of digital content
      were more strongly related when adolescents reported greater confidence with not
      getting caught and higher normative beliefs concerning cyber aggression through
      SNS and mobile phones. In addition, higher levels of attitudes toward the
      permanency of digital content, confidence with not getting caught, beliefs about
      anonymity, and normative beliefs regarding cyber aggression were related to
      greater Time 2 ACA through e-mail, IM, and chatrooms. All findings are discussed
      in the context of adolescents' positive attitudes toward ACA, and an appeal for
      additional research is made to understand more about anonymity in cyberspace.

PMID- 24724732
TI  - Hybrid pressure retarded osmosis-membrane distillation system for power
      generation from low-grade heat: thermodynamic analysis and energy efficiency.
AB  - We present a novel hybrid membrane system that operates as a heat engine capable
      of utilizing low-grade thermal energy, which is not readily recoverable with
      existing technologies. The closed-loop system combines membrane distillation
      (MD), which generates concentrated and pure water streams by thermal separation,
      and pressure retarded osmosis (PRO), which converts the energy of mixing to
      electricity by a hydro-turbine. The PRO-MD system was modeled by coupling the
      mass and energy flows between the thermal separation (MD) and power generation
      (PRO) stages for heat source temperatures ranging from 40 to 80  degrees C and
      working concentrations of 1.0, 2.0, and 4.0 mol/kg NaCl. The factors controlling
      the energy efficiency of the heat engine were evaluated for both limited and
      unlimited mass and heat transfer kinetics in the thermal separation stage. In
      both cases, the relative flow rate between the MD permeate (distillate) and feed
      streams is identified as an important operation parameter. There is an optimal
      relative flow rate that maximizes the overall energy efficiency of the PRO-MD
      system for given working temperatures and concentration. In the case of unlimited
      mass and heat transfer kinetics, the energy efficiency of the system can be
      analytically determined based on thermodynamics. Our assessment indicates that
      the hybrid PRO-MD system can theoretically achieve an energy efficiency of 9.8%
      (81.6% of the Carnot efficiency) with hot and cold working temperatures of 60 and
      20  degrees C, respectively, and a working solution of 1.0 M NaCl. When mass and
      heat transfer kinetics are limited, conditions that more closely represent actual
      operations, the practical energy efficiency will be lower than the theoretically
      achievable efficiency. In such practical operations, utilizing a higher working
      concentration will yield greater energy efficiency. Overall, our study
      demonstrates the theoretical viability of the PRO-MD system and identifies the
      key factors for performance optimization. 

PMID- 24724733
TI  - Benzannulation via ruthenium-catalyzed diol-diene [4+2] cycloaddition: one- and
      two-directional syntheses of fluoranthenes and acenes.
AB  - A new benzannulation protocol is described and applied to the synthesis of
      polycyclic aromatic hydrocarbons. Ruthenium(0)-catalyzed diol-diene [4+2]
      cycloaddition delivers cyclohex-1-ene-4,5-diols, which are subject to
      aromatization upon dehydration or Nicholas diol deoxydehydration. Employing diol
      and tetraol reactants, benzannulation can be conducted efficiently in one- and
      two-directional modes, respectively, as illustrated in the construction of
      substituted fluoranthenes and acenes. 

PMID- 24724734
TI  - Role of bone-marrow- and non-bone-marrow-derived receptor for advanced glycation
      end-products (RAGE) in a mouse model of diabetes-associated atherosclerosis.
AB  - RAGE (receptor for advanced glycation end-products) is expressed on multiple cell
      types implicated in the progression of atherosclerosis and plays a role in DAA
      (diabetes-associated atherosclerosis). The aim of the present study was to
      determine the relative role of either BM (bone marrow)- or non-BM-derived RAGE in
      the pathogenesis of STZ (streptozotocin)-induced DAA. Male ApoE (apolipoprotein
      E)-null (ApoE-/-:RAGE+/+) and ApoE:RAGE-null (ApoE-/-:RAGE-/-) mice at 7 weeks of
      age were rendered diabetic with STZ. At 8 weeks of age, ApoE-/- and ApoE-/-:RAGE
      /- control and diabetic mice received BM from either RAGE-null or RAGE-bearing
      mice, generating various chimaeras. After 10 and 20 weeks of diabetes, mice were
      killed and gene expression and atherosclerotic lesion formation were evaluated
      respectively. Deletion of RAGE in either the BM cells or non-BM cells both
      resulted in a significant attenuation in DAA, which was associated with reduced
      VCAM-1 (vascular cell adhesion molecule-1) expression and translated into reduced
      adhesion in vitro. In conclusion, the results of the present study highlight the
      importance of both BM- and non-BM-derived RAGE in attenuating the development of
      DAA.

PMID- 24724735
TI  - Spontaneous Dissociation of Fluocinolone Acetonide Sustained Release Implant
      (Retisert) with Dislocation into the Anterior Chamber.
AB  - PURPOSE: To report two cases of spontaneous Retisert implant dissociation with
      dislocation of the medication reservoir into the anterior chamber. DESIGN AND
      METHODS: Case reports. RESULTS: Two patients with chronic, noninfectious uveitis
      following Retisert implantation between 6 and 7 years prior presented with a
      complaint of a "white spot" in their right eyes. Both patients had previous pars
      plana vitrectomies. Anterior segment examination revealed a dislocated medication
      reservoir of the Retisert implant in the inferior portion of anterior chamber
      with associated reservoir-corneal endothelial touch and stromal edema. The
      reservoirs were subsequently retrieved via a pars plana approach and removed from
      the anterior chamber through a corneal incision. CONCLUSIONS: Spontaneous
      dissociation of the Retisert implant with dislocation of the medication reservoir
      into the anterior chamber can be a late complication of Retisert implantation.
      Eye care professionals and patients should be aware of this complication,
      particularly with long-term intraocular retention of this device.

PMID- 24724736
TI  - Regulatory focus and burnout in nurses: The mediating effect of perception of
      transformational leadership.
AB  - This correlation study investigated the relationship between nurses' regulatory
      focus and burnout, as mediated by their perceptions of transformational
      leadership, using a cross-sectional research design with anonymous
      questionnaires. In July-August 2012, data were collected from 378 nurses from
      three hospitals in Shaanxi Province, China, using self-report questionnaires for
      measuring the nurses' regulatory focus, their level of burnout and their
      perception of whether the leadership of their supervisor was transformational.
      Structural equation modelling and bootstrapping procedures were used to identify
      the mediating effect of their perceptions of transformational leadership. The
      results supported our hypothesized model. The type of regulatory focus emerged as
      a significant predictor of burnout. Having a perception of transformational
      leadership partially mediated the relationship between regulatory focus and
      burnout. Having a promotion focus reduced burnout when the participants perceived
      transformational leadership, whereas having a prevention focus exhibited the
      opposite pattern. The mediating effect of the perception of transformational
      leadership suggests that a promotion focus may help diminish burnout, directly
      and indirectly. Nurse managers must be aware of the role of a regulatory focus
      and cultivate promotion focus in their followers. 

PMID- 24724737
TI  - Water-stable, adaptive, and electroactive supramolecular ionic material and its
      application in biosensing.
AB  - Developing water-stable and adaptive supramolecular materials is of great
      importance in various research fields. Here, we demonstrate a new kind of water
      stable, adaptive, and electroactive supramolecular ionic materials (SIM) that is
      formed from the aqueous solutions of imidazolium-based dication and dianionic dye
      (i.e., 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid), ABTS) through
      ionic self-assembly. The formed SIM not only shows good thermostability and
      unique optical and electrochemical properties that are raised from precursors of
      the SIM, but also exhibits good water-stability, salt-stability, and adaptive
      encapsulation properties toward some heterocyclic cationic dye molecules. UV-vis
      and FT-IR results demonstrate that this encapsulation property is essentially
      based on the electrostatic interactions between the guest dye molecules and ABTS
      in the SIM. The application of the SIM prepared here is illustrated by the
      development of a new electrochemical sensor for NADH sensing at a low potential.
      This study not only opens a new avenue to the preparation of the supramolecular
      materials, but also provides a versatile platform for electrochemical
      (bio)sensing. 

PMID- 24724738
TI  - Can a stressed oncologist be good in a consultation? A qualitative study on the
      oncologists' perception.
AB  - The aim of this exploratory study was to examine how the working conditions and
      job stress of private practice oncologists (PPOs) affect their interaction with
      patients. Data for the study were collected through semi-structured interviews
      with PPOs selected based on purposeful sampling criteria. The data were evaluated
      using content analysis. Factors perceived by PPOs to influence their level of
      stress and patient care were some of their own personal characteristics as well
      as working conditions both within and outside their practices. Apart from being
      able to name specific stressors (e.g., dysfunctional organisational workflow and
      interruptions during medical encounters), the oncologists also mentioned
      individual and organisational resources (e.g., professional experience, well
      educated nurses and good work organisation) for coping with job stress and
      improving interaction with patients. Within this study, we identified some
      obstacles on the individual and organisational level for good patient care, as
      working conditions which might lead to time pressure and stress, which
      subsequently have an impact on quality in patient care (e.g., less time for
      personal issues during patient consultations). Future stress research should
      conduct a more in-depth investigation of these and other interventions at both
      the individual and organisational levels in order to improve patient care.

PMID- 24724739
TI  - Fractional poisson--a simple dose-response model for human norovirus.
AB  - This study utilizes old and new Norovirus (NoV) human challenge data to model the
      dose-response relationship for human NoV infection. The combined data set is used
      to update estimates from a previously published beta-Poisson dose-response model
      that includes parameters for virus aggregation and for a beta-distribution that
      describes variable susceptibility among hosts. The quality of the beta-Poisson
      model is examined and a simpler model is proposed. The new model (fractional
      Poisson) characterizes hosts as either perfectly susceptible or perfectly immune,
      requiring a single parameter (the fraction of perfectly susceptible hosts) in
      place of the two-parameter beta-distribution. A second parameter is included to
      account for virus aggregation in the same fashion as it is added to the beta
      Poisson model. Infection probability is simply the product of the probability of
      nonzero exposure (at least one virus or aggregate is ingested) and the fraction
      of susceptible hosts. The model is computationally simple and appears to be well
      suited to the data from the NoV human challenge studies. The model's deviance is
      similar to that of the beta-Poisson, but with one parameter, rather than two. As
      a result, the Akaike information criterion favors the fractional Poisson over the
      beta-Poisson model. At low, environmentally relevant exposure levels (<100),
      estimation error is small for the fractional Poisson model; however, caution is
      advised because no subjects were challenged at such a low dose. New low-dose data
      would be of great value to further clarify the NoV dose-response relationship and
      to support improved risk assessment for environmentally relevant exposures. 

PMID- 24724740
TI  - Correlation between liver volume, portal vascular anatomy, and hepatic perfusion
      in dogs with congenital portosystemic shunt before and after placement of ameroid
      constrictors.
AB  - OBJECTIVE: To correlate changes in hepatic volume, hepatic perfusion, and
      vascular anatomy of dogs with congenital extrahepatic portosystemic shunts,
      before and after attenuation with an ameroid constrictor. STUDY DESIGN:
      Prospective study. ANIMALS: Dogs (n = 22) with congenital extrahepatic
      portosystemic shunts. METHODS: CT angiography and perfusion scans were performed
      before and after attenuation of a portosystemic shunt with an ameroid
      constrictor. Changes in hepatic volume, hepatic perfusion, and vascular anatomy
      were measured. Portal scintigraphy was performed in 8 dogs preoperatively and 22
      dogs postoperatively. RESULTS: Dogs with smaller preoperative liver volumes had
      greater increases in liver volume postoperatively compared with those with larger
      preoperative liver volumes. Hepatic arterial fraction was increased in dogs
      preoperatively and returned to normal range after shunt attenuation, and was
      correlated with increase in liver size and decreased shunt fraction. Three dogs
      with no visible portal vasculature preoperatively developed portal branches
      postoperatively. CONCLUSIONS: Dogs with smaller preoperative liver volumes had
      the largest postoperative increase in liver volume. Hepatic arterial perfusion
      and portal scintigraphy correlate with liver volume and are indicators of
      successful shunt attenuation. Dogs without visible vasculature on CT angiography
      had visible portal vasculature postoperatively.

PMID- 24724741
TI  - Differential responses of three grapevine cultivars to Botryosphaeria dieback.
AB  - Botryosphaeria dieback is a fungal grapevine trunk disease that represents a
      threat for viticulture worldwide due to the decreased production of affected
      plants and their premature death. This dieback is characterized by a typical wood
      discoloration called brown stripe. Herein, a proteome comparison of the brown
      striped wood from Botryosphaeria dieback-affected standing vines cultivars
      Chardonnay, Gewurztraminer, and Mourvedre was performed. The transcript analysis
      for 15 targeted genes and the quantification of both total phenolics and specific
      stilbenes were also performed. Several pathogenesis-related proteins and members
      of the antioxidant system were more abundant in the brown striped wood of the
      three cultivars, whereas other defense-related proteins were less abundant.
      Additionally, total phenolics and some specific stilbenes were more accumulated
      in the brown striped wood. Strongest differences among the cultivars concerned
      proteins of the primary metabolism, which looked to be particularly impaired in
      the brown striped wood of 'Chardonnay'. Low abundance of some proteins involved
      in defense response probably contributes to make global response insufficient to
      avoid the symptom development. The differential susceptibility of the three
      grapevine cultivars could be linked to the diverse expression of various proteins
      involved in defense response, stress tolerance, and metabolism.

PMID- 24724742
TI  - Identification of the major HHV-6 antigen recognized by cerebrospinal fluid IgG
      in multiple sclerosis.
AB  - BACKGROUND AND PURPOSE: Different data show an association between human
      herpesvirus 6 (HHV-6) and multiple sclerosis (MS). Intrathecal anti-HHV-6
      immunoglobulin G (IgG) was detected in MS patients, but the antigen recognized by
      cerebrospinal fluid (CSF) IgG has not been characterized yet. Our objective was
      to identify the HHV-6 antigens recognized by IgG present in the CSF of patients
      with MS. METHODS: Cerebrospinal fluid IgG of 15 MS patients and eight patients
      with other neurological diseases was purified on protein G Sepharose columns.
      Purified IgG from every patient was linked to a CNBr-activated Sepharose 4B
      column. Fifty micrograms of viral extract was applied to each column. Bound
      proteins were eluted and analysed by SDS-PAGE and silver staining. The viral
      protein was characterized by mass spectrometry. RESULTS: A protein of 150 kD was
      eluted from CSF IgG columns of three of eight patients with primary progressive
      MS and one of seven with relapsing-remitting MS. After digestion and mass
      spectrometry analysis 10 peptides were found with 100% homology with the major
      capsid protein of the HHV-6A. DISCUSSION: These findings confirm the presence of
      anti-HHV-6 IgG in CSF of MS patients, particularly in progressive forms, and
      identify major capsid protein as the major antigen recognized by CSF IgG from MS
      patients.

PMID- 24724743
TI  - Surface-enhanced infrared spectroscopy using nanometer-sized gaps.
AB  - We report on the near-field coupling of individual gold nanoantennas arranged in
      tip-to-tip dimer configuration, leading to strong electromagnetic field
      enhancements in the infrared, which is of great interest for sensing applications
      such as surface-enhanced infrared spectroscopy. We quantitatively evaluated the
      enhancement of vibrational excitations of a 5 nm thick test layer of 4,4'-bis(N
      carbazolyl)-1,1'-biphenyl as a function of different gap sizes. The dimers with
      the smallest gaps under investigation (~3 nm) lead to more than 1 order of
      magnitude higher signal enhancement with respect to gaps of 50 nm width. The
      comparison of experimental data and finite-difference time-domain simulations
      reveals a nonperfect filling of the gaps with sizes below 10 nm, which means that
      morphological information on the nanoscale is obtained additionally to chemical
      information. 

PMID- 24724744
TI  - Wisdom won from illness: the psychoanalytic grasp of human being.
AB  - From its inception psychoanalysis claimed not merely to be an effective therapy
      for psychological suffering, but to shed light on the human condition. But what
      kind of insight does psychoanalysis offer? This paper locates psychoanalysis in
      the western philosophical tradition, arguing that psychoanalysis provides not
      only theoretical wisdom about the human, but practical wisdom of a peculiar kind.
      The human mind, through its self-conscious understanding can be immediately and
      directly efficacious in shaping its own structure.

PMID- 24724745
TI  - Belgian recommendations on ANA, anti-dsDNA and anti-ENA antibody testing.
AB  - Autoantibodies to nuclear antigens, i.e. antinuclear antibodies (ANA), antibodies
      to double-stranded DNA (dsDNA) and extractable nuclear antigens (ENA), are useful
      as diagnostic markers for a variety of autoimmune diseases. In March 2010, the
      Belgian national External Quality Assessment Scheme sent a questionnaire on ANA,
      anti-dsDNA and anti-ENA antibody testing designed by the Dutch EASI (European
      Autoimmunity Standardization Initiative) team, to all clinical laboratories
      performing ANA testing. Virtually all laboratories completed the questionnaire
      (97.7%, 127/130). This paper discusses the results of this questionnaire and
      provides valuable information on the state-of-the-art of ANA, anti-dsDNA and anti
      ENA antibody testing as practiced in the Belgian laboratories. In addition, this
      work presents practical recommendations developed by the members of the advisory
      board of the scheme as a result of the outcome of this study. 

PMID- 24724746
TI  - Nasal symptoms in patients with obstructive sleep apnea and their impact on
      therapeutic compliance with continuous positive airway pressure.
AB  - Continuous positive airway pressure (CPAP) is the first line treatment for
      moderate to severe obstructive sleep apnea syndrome. Despite the high
      effectiveness of this treatment, its use is often limited by suboptimal
      compliance and/or intolerance. Nasal side effects are considered a major cause of
      low therapeutic compliance. At present, there are no data to predict which
      patients will develop CPAP intolerance caused by nasal symptoms and only few
      studies looked at the effect of treatment of nasal symptoms on CPAP compliance.
      The first section of this review focuses on the impact of nasal symptoms (pre
      existing or as a side effect of CPAP) on CPAP compliance/intolerance. The second
      section deals with the effect of nasal symptom treatment on CPAP compliance. 

PMID- 24724747
TI  - Routine implementation of EGFR mutation testing in clinical practice in Flanders:
      'HERMES' project.
AB  - Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) is the
      recommended first-line treatment in metastatic EGFR-mutation-positive non-small
      cell lung cancer (NSCLC) patients. Such a personalized treatment requires fast
      EGFR mutation testing. This study was performed to determine the turn around time
      (TAT) for EGFR mutation testing on tumour samples of NSCLC in the clinical care
      in the region of Antwerp (Belgium). The secondary aim was to determine the
      frequency of EGFR mutations in this Flemish population. Tumour tissue was
      prospectively obtained from lung cancer patients in participating hospitals and
      sent from the local pathology laboratory (lab) to two central laboratories (labs)
      where EGFR-mutation analysis was performed. Results were returned from the
      central labs to the clinicians and the local pathology lab. TAT was defined as
      the interval between the request from the oncologist and the result obtained by
      the oncologist. One hundred and seven specimens were analysed. The clinician got
      the result from the local lab in a median time of 10 days (3-37 days) and from
      the central lab in 9 days (3-29 days). We detected seven mutations (7%) in this
      study population, all occurring in tumours with an adenocarcinoma histology, four
      (57%) in men and five (71%) in (ex-)smokers. There were six exon 19 deletions and
      one L858R mutation. It is possible to implement EGFR-mutation testing with timely
      reporting of the EGFR-mutation status. EGFR-mutation occurs in 7% of Flemish
      patients with NSCLC. Patients with advanced non-squamous NSCLC should be tested
      for EGFR mutation regardless of their gender and smoking history. 

PMID- 24724748
TI  - Treatment with lenalidomide (Revlimid(r)), cyclophosphamide (Endoxan(r)) and
      prednisone (REP) in relapsed/refractory multiple myeloma patients: results of a
      single centre retrospective study.
AB  - Lenalidomide (Revlimid(r)) combined with intermittent dexamethasone (the RD
      regimen) is one of the current standards for treatment of patients with
      relapsed/refractory multiple myeloma (MM). However, since the disease in the
      majority of patients will become resistant to RD, or treatment with RD needs to
      be discontinued due to side effects, we evaluated the combination lenalidomide,
      low-dose oral cyclophosphamide, with prednisone (REP) in patients with
      relapsed/refractory MM previously exposed to RD. For this purpose, we performed a
      single centre retrospective study of the efficacy of REP in 19 patients with
      relapsed/refractory MM. Overall response rate (partial response or better) with
      REP was 68% compared with 83% with RD, but with a shorter time to response with
      the triplet REP. Time to progression after REP was 6 months. Overall the REP
      regimen was better tolerated compared to RD. We conclude that the REP regimen is
      an effective treatment regimen for patients with relapsed/refractory MM with good
      tolerance, warranting further exploration in prospective randomized trials. 

PMID- 24724749
TI  - Epidemiology of pertussis in children of Flanders Belgium: can healthcare
      professionals be involved in the infection?
AB  - Pertussis is a communicable disease whose registration incidence in the Flemish
      region of Belgium has increased since 2003. Originally, this increment was
      obvious only in the province of Antwerp, but since 2012, there has also been an
      increase in the registered cases of pertussis in other Flemish provinces. The
      overall registration incidence for pertussis in Flanders was 5.6 per 100 000 in
      2012. The majority of these cases were identified among young children, but older
      children and adults were also affected. Increased awareness, new diagnostic
      tools, better registration, waning immunity, and circulation of new strains were
      most likely associated with the increase in reporting. Although many of the
      pertussis infections we studied occurred within family units, several healthcare
      workers who had been in contact with young children were also identified as
      sources of pertussis. A number of these were index cases, while others were
      secondary infections. Finally, a fatal neonatal pertussis case is presented to
      illustrate the severity of the disease in young unvaccinated children. 

PMID- 24724750
TI  - Determinants of adherence in a cohort of Belgian HIV patients: a pilot study.
AB  - Since the era of highly active antiretroviral therapy (HAART), HIV is considered
      a chronic disease. Adherence to HAART is crucial for effectiveness. Non-adherence
      negatively impacts patient outcome and the larger economy. However, data on
      adherence among the Belgian HIV cohort are scarce. Therefore, the purpose of this
      pilot study was to identify determinants of adherence among HIV patients treated
      in Belgium. The study was conducted at the Aids Reference Centre of Ghent
      University Hospital between 1 January and 31 December 2012. Sociodemographic data
      were collected, along with the Simplified Medication Adherence Questionnaire
      (SMAQ), the Center for Adherence Support Evaluation (CASE) Adherence Index, the
      EuroQol-6D, the Medical Outcomes Study-HIV (MOS-HIV), the Beck Depression
      Inventory-II, and three neurocognitive complaints screening questions. To date,
      218 patients participated in the study, among whom 173 (79.4%) were male. Mean
      age was 46.0+/-10.6 years and 133 patients (63.9%) were homosexual. According to
      the SMAQ and the CASE, 78.5% and 93.5% of the patients were adherent to
      antiretroviral therapy. Logistic regression analysis revealed that smoking,
      neurocognitive complaints, and female sex were independent determinants of non
      adherence. In conclusion, there is an elevated risk for non-adherence in smokers,
      people experiencing neurocognitive problems, and women in our sample. The latter
      could reflect differences between male and female HIV patients in Belgium.
      Adherence improving initiatives should be tailored to these three risk groups. 

PMID- 24724751
TI  - Acute respiratory distress syndrome after verapamil intoxication: case report and
      literature review.
AB  - Verapamil intoxication is a life-threatening condition that often presents with
      severe hemodynamic instability and requires vasopressor support. There are also
      documented case reports of the development of non-cardiogenic pulmonary oedema
      after verapamil overdose. However, the exact mechanisms responsible for pulmonary
      oedema remain unclear. Here, we describe a 36-year-old woman who was admitted to
      the intensive care unit after ingesting high-dose verapamil and subsequently
      developed acute respiratory distress syndrome soon after hemodynamic
      stabilization. Possible mechanisms are presented after taking into account
      findings in the current literature. Acute respiratory distress syndrome should be
      considered early during the evaluation of patients with verapamil intoxication. 

PMID- 24724752
TI  - Cocaine induced severe muscular weakness.
AB  - Cocaine abuse has been associated with a number of psychiatric, medical and
      neurological complications. Here we report the case of a male patient who
      suffered an episode of severe muscular weakness after cocaine abuse. 

PMID- 24724753
TI  - Arterial hypertension related to the injection of onabotulinumtoxinA in the
      detrusor.
AB  - OBJECTIVE AND IMPORTANCE: We want to report on a first case reported of a 50-year
      old female with repetitive and clinical significant hypertension after each
      injection of onabotulinumtoxinA. This is a retrospective chart review and
      prospective evaluation of the natriuresis and blood pressure at baseline and
      after injection therapy. The aim was to explore the mechanism of action of this
      apparent onabotulinumtoxinA related hypertension. CASE PRESENTATION:
      Retrospectively hypertension appeared after 7 days and vanished after 4-5 months
      following injection of 300 units of onabotulinumtoxinA in the detrusor, bladder
      symptoms disappeared after 2 weeks and reoccurred after 5 months. Urological,
      nephrological, cardiological and endocrinological evaluations were normal.
      INTERVENTION: In the prospective evaluation a 3-day bladder diary at baseline
      revealed a bladder capacity of 131 +/- 57 ml and at 1 month when full effect was
      experienced 173 +/- 50 ml. At 1 month there were no leakages with six episodes of
      intermittent catheterization per day. The 24-hour blood pressure registration
      demonstrated the onset of hypertension at day 7 together with a reversal of the
      urinary sodium/creatinine ratios on the renal function profile. CONCLUSION: The
      increasing natriuresis coinciding with the hypertension is a normal compensatory
      mechanism suggesting that the hypertension has a central cause rather than it is
      caused by haematogenous spreading.

PMID- 24724754
TI  - Removal of an unusual bronchial foreign body: rigid or flexible bronchoscopy?
AB  - Foreign body inhalation is an emergency in pediatric medicine, particularly in
      children before the age of 3 years. Whereas clinical assessment and chest X-ray
      usually guide the diagnosis, rigid bronchoscopy still remains the gold standard
      in terms of management of foreign body inhalation. However, flexible fibroscopy
      can also be quite useful in certain situations. This is illustrated by the
      following case of a young girl with foreign body inhalation in which flexible
      fibroscopy was the only way of removing the foreign object. 

PMID- 24724755
TI  - A challenging case of septic sacroiliitis with psoas involvement.
AB  - OBJECTIVE AND IMPORTANCE: We report on a rare case of septic arthritis of the
      sacroiliac joint in a young patient without apparent predisposing factors.
      CLINICAL PRESENTATION: A 22-year-old female presented with severe right pelvic
      and gluteal pain and systemic illness. She had a recent diagnosis of bilateral
      sacroiliitis. INTERVENTION: Systemic illness quickly subsided after initiation of
      intravenous antibiotic treatment. Subsequently, gluteal pain gradually
      diminished. CONCLUSION: Pyogenic sacroiliitis should be taken into account in
      patients with sacroiliitis and fever onset. Magnetic resonance imaging shows
      signal anomalies well beyond disappearance of symptoms, which may or may not
      require prolonged antibiotic therapy.

PMID- 24724756
TI  - Spontaneous regression of a hepatoma with ring calcification.
AB  - The authors report a 74-year-old man with chronic hepatitis C-related cirrhosis
      and end-stage renal disease undergoing maintenance haemodialysis who was
      diagnosed with hepatoma. The hepatoma spontaneously regressed with significantly
      decreased serum alpha-fetoprotein level without any treatment during the
      subsequent 4-year follow-up period. However, recurrent hepatomas over bilateral
      hepatic lobes were evident thereafter, and the patient died later due to hepatic
      failure. Hepatoma with ring calcification is extremely rare and considered poor
      differentiation with high risk for recurrence. Spontaneous regression of hepatoma
      is also rare, while spontaneous regression occurring in a hepatoma with ring
      calcification is never reported. The definite mechanisms causing spontaneous
      regression of hepatomas remain unclear, but an immune response toward hepatoma
      induced by alpha-fetoprotein might play an important role. 

PMID- 24724757
TI  - Case report, aetiology, and treatment of an acquired long-QT syndrome.
AB  - Acquired long-QT syndrome is an iatrogenic disorder, usually induced by drugs,
      which can cause life-threatening arrhythmias. We present a case report on an
      acquired long-QT syndrome with an interesting confluence of circumstances, and
      comment on aetiology and treatment. 

PMID- 24724758
TI  - Metastatic signet-ring cell carcinoma of unknown primary origin.
AB  - About 3-5% of metastatic cancers originate from an unknown primary origin. Some
      have a signet-ring cell (SRC) component. We report the medical history of three
      patients with SRC carcinoma expressing both the oestrogen (ER) and progesterone
      receptors (PR). Although no primary breast cancer could be identified, we
      considered these three patients as having metastatic breast cancer. All of them
      were therefore treated with standard breast anti-hormonal therapies and all
      demonstrated benefit. The pitfalls of clinical presentation, diagnostic work-up,
      and treatment are discussed. 

PMID- 24724759
TI  - Pulmonary arterio-venous malformations in a patient with a novel mutation in exon
      10 of the ACVRL1 gene.
AB  - Mutations of the ACVRL1 gene are a cause of hereditary haemorrhagic
      telangiectasia (HHT) type 2. In this case report, we present a patient with
      isolated pulmonary arterio-venous malformations (PAVMs) without other diagnostic
      criteria for HHT and a novel mutation in exon 10 of the ACVRL1 gene. Other
      mutations in exon 10 of ACVRL1 have been linked to the development of pulmonary
      artery hypertension, but PAVMs are a rare manifestation of HHT associated with
      ACVRL1 mutations. A disrupted endothelial TGF-beta/BMP signaling cascade
      underlies the pathogenesis of HHT, but the exact mechanism of the disease remains
      unelucidated. In particular, the factors that influence the variable clinical
      presentation are not fully understood. 

PMID- 24724760
TI  - Disseminated Mycobacterium genavense infection in a patient with
      immunosuppressive therapy and lymphoproliferative malignancy.
AB  - We present the case of a 51-year-old woman who presented a right supraclavicular
      mass corresponding to lymphadenitis with atypical mycobacterium (Mycobacterium
      genavense). Later, she developed subcutaneous purulent small nodules containing
      the same germ. The presence of this mycobacterium was in the context of recurrent
      peripheral T-cell lymphoma and immunosuppressive therapy for seronegative
      inflammatory polyarthritis. 

PMID- 24724761
TI  - Spontaneous pneumomediastinum and epidural pneumatosis after oral ecstasy
      consumption.
AB  - A 19-year-old man was admitted with acute dyspnoea. Physical examination revealed
      subcutaneous emphysema in the cervical and thoracic area. This was further
      confirmed by the total body computed tomography that also demonstrated
      mediastinal emphysema. Epidural pneumatosis of the thoracis spine was also
      evident. There was no history of trauma, but well of a recent oral ecstasy
      consumption during a techno rave party, associated with intense dancing and
      jumping. Clinical course was favourable with conservative therapy. 

PMID- 24724762
TI  - Osmotic demyelination syndrome caused by normal saline correction in a patient
      admitted for gastric ulcer bleeding.
AB  - A 61-year-old male had osmotic demyelination syndrome caused by rapid correction
      of gastric ulcer bleeding and vomiting related hyponatraemia with normal saline.
      It is rare to see severe hyponatraemia caused by gastric ulcer bleeding and
      vomiting. Hypokalaemia may be the determinant predisposing factor. There was no
      specific brain image finding until 17 days after the initial clinical
      presentation of this disease. Brain diffusion weighted MRI series did not help
      for the early diagnosis in this case. Outcome of this case may be more favourable
      if we corrected his hyponatraemia with half-saline or other hypotonic saline and
      close monitored serum sodium level, and relowered with dextrose water and
      desmopressin once we observed that the correction rate of hyponatraemia was
      beyond the recommended rate. 

PMID- 24724763
TI  - Abdominal actinomycosis: a rare complication after cholecystectomy.
AB  - We present a single case of abdominal actinomycosis occurring in a 74-year-old
      female with a history of cholecystectomy 42 months before presentation. In a
      review of the literature, we present risk factors, clinical characteristics,
      diagnosis, and treatment of this infection. Abdominal actinomycosis is a rare,
      chronic, granulomatous infection characterized by the release of 'sulphur
      granules'. Actinomyces species should always be part of the differential
      diagnosis of patients presenting with a history of surgical or invasive
      procedures, presenting with an abdominal mass. Computed tomography (CT)-guided
      aspiration with or without core biopsy of this mass is a useful investigation.
      Diagnosis is often difficult: In less than 10% of cases, the diagnosis is made
      pre-operatively. Definitive diagnosis is often based on histochemical,
      macroscopic, and microscopic examination of tissue specimens. The disease should
      be treated with high doses of intravenous penicillin for 2-6 weeks followed by
      oral therapy for at least 6-12 months. 

PMID- 24724764
TI  - Body fat% is also a potentially poor individual measure for health in children.

PMID- 24724765
TI  - Reply-body fat% is also a potentially poor individual measure for health in
      children.

PMID- 24724766
TI  - Multivitamin/mineral supplement contribution to micronutrient intakes in the
      United States, 2007-2010.
AB  - OBJECTIVE: Multivitamin/mineral (MVMM) supplements are the most common dietary
      supplements consumed in the United States; however, intake data specific to how
      MVMM use contributes to micronutrient intakes among Americans are absent from the
      current scientific literature. METHODS: This analysis aimed to assess
      contributions of micronutrients to usual intakes derived from MVMM supplements
      and to compare those intakes to the dietary reference intakes for US residents
      aged >= 4 years according to the National Health and Nutrition Examination Survey
      (NHANES) 2007-2010 (n = 16,444). We used the National Cancer Institute method to
      assess usual intakes of 21 micronutrients. RESULTS: Our results showed that 51%
      of Americans consumed MVMM supplements containing >= 9 micronutrients. Large
      portions of the population had total usual intakes (food and MVMM supplement use)
      below the estimated average requirement for vitamins A (35%), C (31%), D (74%),
      and E (67%) as well as calcium (39%) and magnesium (46%). Only 0%, 8%, and 33% of
      the population had total usual intakes of potassium, choline, and vitamin K above
      the adequate intake when food and MVMM use was considered. The percentage of the
      population with total intakes greater than the tolerable upper intake level (UL)
      was very low for all nutrients; excess intakes of zinc were the highest (3.5%)
      across the population of all of the nutrients assessed in NHANES. CONCLUSIONS: In
      large proportions of the population, micronutrient sufficiency is currently not
      being achieved through food solutions for several essential vitamins and
      minerals. Use of age- and gender-specific MVMM supplements may serve as a
      practical means to increase the micronutrient status in subpopulations of
      Americans while not increasing intakes above the UL.

PMID- 24724767
TI  - Randomized controlled trial of a protein substitute with prolonged release on the
      protein status of children with phenylketonuria.
AB  - OBJECTIVE: To examine whether a phenylalanine-free protein substitute with
      prolonged release may be beneficial to the protein status of children with
      phenylketonuria (PKU) compared to conventional substitutes. METHODS: Sixty
      children with PKU, 7 to 16 years of age, were randomly allocated to receive
      either a prolonged-release (test) or the current conventional protein substitute
      for 30 days. Subjects were additionally sex and age matched with 60 subjects with
      mild hyperphenylalaninemia and 60 unaffected subjects. The protein status in
      children with PKU was assessed by albumin, transthyretin, and retinol-binding
      protein (RBP), and changes throughout the trial period were the primary outcome
      measures. RESULTS: Children with PKU did not differ in anthropometry from
      children with mild hyperphenylalaninemia or unaffected children but they ingested
      lower amounts of proteins (p < 0.01). No differences occurred throughout the
      trial between or within children with PKU who received the test or conventional
      substitute for macronutrient intake. Albumin and RBP concentrations were within
      the age-specific reference range for all children. The rate of protein
      insufficiency (transthyretin concentration less than 20 mg/dL) did not differ
      statistically between children receiving test or conventional substitute
      (recruitment 51.8% vs 53.6%; end of the trial 44.4% vs 50.0%) but mean
      transthyretin recovered over 20 mg/dL in children who received the test
      substitute, increasing from 19.1 to 20.7 mg/dL (mean change, 1.6 mg/dL; 95%
      confidence interval 0.4 to 2.8 mg/dL). In children receiving conventional
      substitute mean transthyretin changed from 19.0 to 19.2 mg/dL (0.2; -0.2 to 0.6)
      mg/dL. CONCLUSIONS: Protein substitutes with prolonged release might be
      beneficial to protein status in children with phenylketonuria.

PMID- 24724768
TI  - Dietary glycemic index, glycemic load, and nutritional correlates in free-living
      elderly Brazilians: a population-based survey.
AB  - OBJECTIVES: To investigate the association of dietary glycemic index (GI) and
      glycemic load (GL) with nutrient intake and to describe the foods that contribute
      to dietary GI and GL in elderly subjects. METHODS: This is a cross-sectional
      population-based survey performed in 2003, which enrolled 804 free-living
      Brazilian subjects aged 60 years or older. Dietary intake was measured by a
      single 24-hour dietary recall applied at the subjects' homes. The usual dietary
      GI and GL as well as the usual energy and nutrient intakes were estimated using
      external variance components. Dietary GI and GL were categorized in tertiles and
      the usual mean of nutrient intake was described accordingly. Linear association
      between dietary GI and GL and nutrient intake was investigated before and after
      energy adjustment. Foods that contributed with at least 1% of dietary GI and GL
      were described. RESULTS: Dietary GI was positively associated with starch, total
      fat, monounsaturated fatty acids (MUFA), and polyunsaturated fatty acids (PUFA)
      and inversely associated with total sugar, protein, fiber, and calcium. Dietary
      GL was strongly and positively associated with total and available carbohydrates,
      starch, and total sugar and inversely associated with protein, total fat, MUFA,
      PUFA, and cholesterol. White breads and white rice were the major contributors to
      dietary GI and GL in the studied population. CONCLUSION: Dietary GI and GL are
      important indicators of overall quality and quantity of carbohydrates from
      elderly Brazilians diet and are also associated with other macronutrients such as
      protein, fat, and fiber. The overall dietary GI and GL reflects other dietary
      aspects, such as composition of the diet and combination of foods consumed.

PMID- 24724769
TI  - Dietary patterns are associated with body mass index and bone mineral density in
      Chinese freshmen.
AB  - OBJECTIVE: Our objective was to examine associations between dietary patterns and
      body mass index (BMI) and bone mineral density (BMD) in Chinese freshmen.
      METHODS: A cross-sectional study was done in 1319 college freshmen (aged 18.1 +/-
      1.2 years old). Diet was assessed by using a validated self-administrated food
      frequency questionnaire. Blood pressure, weight, height, waist circumference, and
      hip circumference were measured and bone measurements were done using
      Quantitative Ultrasound System. RESULTS: Four dietary patterns were identified by
      factor analysis: Western food, animal protein, calcium food, and Chinese
      traditional patterns. The prevalence of overweight/obesity and
      osteopenia/osteoporosis were 8.2% (108/1319) and 28.1% (371/1319). The highest
      tertile of Western food pattern scores had greater odds of overweight/obesity
      (highest vs. lowest tertile, odds ratio [OR] = 2.00, 95% confidence interval
      [CI], 1.24-3.22), and the highest tertile of Chinese traditional pattern scores
      had lower risk of overweight/obesity (highest vs. lowest tertile, OR = 0.65, 95%
      CI, 0.53-0.80) in an adjusted model. The calcium food pattern and Chinese
      traditional pattern were negatively associated with the risk of
      osteopenia/osteoporosis (highest vs. lowest tertile, OR = 0.59, 95% CI, 0.41
      0.87; OR = 0.78, 95% CI, 0.55-0.89) after adjusting for confounders. CONCLUSION:
      These findings suggested that there was a positive correlation between Chinese
      traditional dietary pattern and healthy BMI and BMD and that this same
      association existed between calcium food pattern and BMD in Chinese freshmen. In
      contrast, the Western-style diet was negatively correlated with healthy BMI in
      Chinese freshmen.

PMID- 24724771
TI  - Milk protein-based infant formula containing rice starch and low lactose reduces
      common regurgitation in healthy term infants: a randomized, blinded, and
      prospective trial.
AB  - OBJECTIVE: Spit-up (regurgitation) reduction with prethickened milk protein-based
      infant formulas containing rice starch has been clinically demonstrated in
      infants with heavy spit-ups but not in otherwise healthy normal infants with
      common spit-ups. The objective of this study was to evaluate growth,
      gastrointestinal tolerance, and efficacy to reduce common spit-up in normal,
      healthy term infants fed an investigational rice starch prethickened lactose-free
      milk protein-based infant formula. METHODS: This double-blind, randomized,
      parallel study evaluated the investigational rice starch prethickened lactose
      free (low lactose < 100 mg/L) milk protein-based infant formula compared to a
      standard, commercially available, iso-nutrient, lactose-containing (100% of
      carbohydrate) milk-based infant formula (control) for growth and gastrointestinal
      tolerance in healthy term infants (n = 132/group) fed from 14 +/- 3 days to 112
      days of age. Data were classified and analyzed as evaluable (EV; subjects
      completing study per protocol) or intent-to-treat data (ITT; all subjects with
      available data). RESULTS: Growth as indicated by weight gain (primary variable)
      and formula intake were not significantly different (p > 0.05) between feeding
      groups (EV or ITT). Though both formulas were well tolerated, spit-up frequency
      was significantly lower (p < 0.05) in the rice versus control group by 53% at 28
      days of age, 54% at 56 days, 48% at 84 days, and 32% at 112 days (EV).
      Importantly, infants in the rice group were 1.6 to 1.8 times more likely to
      report zero spit-up than infants in the control group. The rice group also had
      higher percentages of soft and yellow stools. CONCLUSIONS: The rice starch
      prethickened lactose-free milk protein-based formula (rice) supported normal
      growth and safe use as the sole source of feeding for normal infants over the
      first 4 months of life. The rice formula was efficacious in providing a
      clinically relevant reduction of spit-up frequency in otherwise healthy term
      infants.

PMID- 24724770
TI  - Low dietary vitamin D in mid-life predicts total mortality in men with
      hypertension: the Honolulu heart program.
AB  - BACKGROUND: Vitamin D deficiency was associated with total mortality in previous
      epidemiological studies. Little is known about the effects of dietary vitamin D
      intake on mortality. We examined the association between mid-life dietary vitamin
      D intake and 45-year total mortality. METHODS: The Honolulu Heart Program is a
      longitudinal cohort study of 8006 Japanese American men in Hawaii aged 45 to 68
      at baseline (1965-1968). Mid-life dietary vitamin D intake was calculated from 24
      hour dietary recall using Nutritionist IV v3 software. We divided subjects into
      quartiles of dietary vitamin D. Total mortality data were available over 45 years
      through 2010. RESULTS: Age-adjusted total mortality rates were higher in the
      lower quartiles of dietary vitamin D intake compared to the highest (p for trend
      = 0.011). Using Cox regression, low dietary vitamin D was significantly
      associated with total mortality; quartile (Q) 1 hazard ratio (HR) = 1.14, 95%
      confidence interval (95% CI) = 1.07-1.22, p < 0.001; Q2 HR = 1.11, 95% CI = 1.04
      1.18, p = 0.002; and Q3 HR = 1.08, 95% CI = 1.01-1.15, p = 0.027; Q4 = reference.
      After adjusting for age, kilocalories, cardiovascular risk factors, and prevalent
      chronic diseases, only Q2 remained significant (HR = 1.08, 95% CI = 1.00-1.15, p
      = 0.037). Among hypertensive subjects only, those in the lower 2 quartiles had
      higher total mortality; Q1 HR = 1.12, 95% CI = 1.01-1.25, p = 0.039, and Q2 HR =
      1.13, 95% CI = 1.02-1.26, p = 0.025, compared to Q4. There was no significant
      relationship in subjects without hypertension. CONCLUSIONS: Low dietary vitamin D
      intake in mid-life was a weak predictor of total mortality over 45 years of
      follow-up. We found a significant association between low dietary vitamin D
      intake and higher total mortality only among hypertensive subjects. Vitamin D may
      have cardioprotective effects.

PMID- 24724772
TI  - Assessment of dietary intake among Inuvialuit in Arctic Canada using a locally
      developed quantitative food frequency questionnaire.
AB  - OBJECTIVE: Inuvialuit in Arctic Canada are experiencing a nutritional and
      lifestyle transition, characterized by a declining consumption of traditional
      foods, increased consumption of non-nutrient-dense store-bought foods (NNDF), and
      reduced levels of physical activity with a concurrent rise in chronic diseases.
      The aim of the present study was to determine dietary intake of Inuvialuit adults
      in the Northwest Territories, Canada, using a culturally specific, validated
      quantitative food frequency questionnaire (QFFQ). METHODS: A cross-sectional
      dietary survey of 213 randomly selected adults (>=19 years) was conducted in 3
      remote communities in the Northwest Territories. Nonparametric analysis was used
      to compare mean nutrient intake, dietary inadequacy, and differences in nutrient
      density among men and women. Data were also analyzed to determine the top food
      groups contributing to energy and selected nutrients. RESULTS: With response
      rates of 65% to 85%, 43 men (mean age 43.2 +/- 12.8) and 170 women (mean age 44.7
      +/- 13.9) completed the QFFQ. Mean daily energy intakes for men were 3478 +/-
      1474 kcal and for women they were 3299 +/- 1653 kcal. For both sexes, protein,
      carbohydrates, and fat provided approximately 16%, 47%, and 28% of energy intake,
      respectively. NNDFs were the top contributors to energy (39%), fat (40%),
      carbohydrate (54%), sugar (74%), and sodium (23%) intake. Total traditional foods
      from the land, sea, and sky such as polar bear and wild birds contributed 11% of
      energy and 41% of protein intake. Most participants' daily intakes were below
      recommended levels for dietary fiber; vitamins A, E, and D; potassium; and
      magnesium. Mean daily energy, saturated fat, and sodium intakes exceeded
      recommendations. CONCLUSIONS: We identified nutrient inadequacies and
      characterized food consumption among Inuvialuit. These data support nutritional
      interventions that encourage consumption of traditional foods. The cultural and
      ethnic differences in Canadian Arctic populations require specific tailoring of
      public health interventions and policy using population specific tools to meet
      local needs.

PMID- 24724773
TI  - Comparative analysis of approaches for assessing energy intake underreporting by
      female bariatric surgery candidates.
AB  - OBJECTIVE: To test six variations in the Goldberg equation for evaluating the
      underreporting of energy intake (EI) among obese women on the waiting list for
      bariatric surgery, considering variations in resting metabolic rate (RMR),
      physical activity, and food intake levels in group and individual approaches.
      METHODS: One hundred obese women aged 20 to 45 years (33.3 +/- 6.08) recruited
      from a bariatric surgery waiting list participated in the study. Underreporting
      assessment was based on the difference between reported energy intake, indirect
      calorimetry measurements and RMR (rEI:RMR), which is compatible with the
      predicted physical activity level (PAL). Six approaches were used for defining
      the cutoff points. The approaches took into account variances in the components
      of the rEI:RMR = PAL equation as a function of the assumed PAL, sample size (n),
      and measured or estimated RMR. RESULTS: The underreporting percentage varied from
      55% to 97%, depending on the approach used for generating the cutoff points. The
      ratio rEI:RMR and estimated PAL of the sample were significantly different (p =
      0.001). Sixty-one percent of the women reported an EI lower than their RMR. The
      PAL variable significantly affected the cutoff point, leading to different
      proportions of underreporting. The RMR measured or estimated in the equation did
      not result in differences in the proportion of underreporting. The individual
      approach was less sensitive than the group approach. CONCLUSION: RMR did not
      interfere in underreporting estimates. However, PAL variations were responsible
      for significant differences in cutoff point. Thus, PAL should be considered when
      estimating underreporting, and even though the individual approach is less
      sensitive than the group approach, it may be a useful tool for clinical practice.

PMID- 24724774
TI  - Effects of whey protein and resistance exercise on body composition: a meta
      analysis of randomized controlled trials.
AB  - OBJECTIVES: The objective of the present meta-analysis was to examine the effect
      of whey protein (WP), with or without resistance exercise, on body weight and
      body composition in randomized controlled trials (RCTs) conducted in generally
      healthy adult study populations. METHODS: A comprehensive literature search was
      conducted to identify RCTs that investigated WP (concentrate, isolate, or
      hydrolystate) and body weight, body mass index (BMI), body fat, lean body mass
      (LBM), fat-free mass (FFM), and waist circumference. Random effects meta-analyses
      were conducted to generate weighted group mean differences (WGMD) for between
      group comparisons (WP vs other protein sources or carbohydrates) and within-WP
      group comparisons (i.e., differences from baseline to trial end). Studies were
      classified into 2 distinct groups-WP as a supplement without dietary modification
      (WPS) and WP as a replacement for other sources of calories (WPR)-and were meta
      analyzed separately. Subgroup analyses included examining the effect of
      resistance exercise and type of WP on the relationship between WP and body
      composition. RESULTS: Fourteen RCTs were included, with a total of 626 adult
      study completers. Five studies examined the effects of WPR and the remaining 9
      studies examined the effects of WPS. Body weight (WGMD: -4.20 kg, 95% confidence
      interval [CI], -7.67, -0.73) and body fat (WGMD: -3.74 kg, 95% CI, -5.98, -1.50)
      were significantly decreased from baseline in the WPR within-group analyses. In
      the between-group analyses, the effects of WP were more favorable when compared
      with carbohydrates than protein sources other than whey, although findings did
      not reach statistical significance. Results from the subgroup analyses indicated
      a statistically significant increase in LBM (WGMD: 2.24 kg, 95% CI, 0.66, 3.81)
      among studies that included a resistance exercise component along with WP
      provision. CONCLUSION: The current body of literature supports the use of WP,
      either as a supplement combined with resistance exercise or as part of a weight
      loss or weight maintenance diet, to improve body composition parameters.

PMID- 24724775
TI  - Consumer usage and reasons for using dietary supplements: report of a series of
      surveys.
AB  - OBJECTIVE: Consumer usage of dietary supplements is prevalent in the United
      States, and total usage is higher than reported in recent National Health and
      Nutrition Examination Surveys (NHANES), because these surveys capture usage only
      in the 30 days prior to the respondent's interview and do not capture occasional
      and seasonal use throughout the year. We report data from a series of consumer
      surveys on the full extent of dietary supplement use, on the reasons for
      supplement use, and on the products most commonly taken, as well as other health
      habits of supplement users. METHODS: The Council for Responsible Nutrition (CRN),
      a trade association of the dietary supplement industry, has contracted with Ipsos
      Public Affairs to conduct consumer surveys annually since 2000. The surveys have
      been administered online since 2007 to about 2000 subjects each year. We report 5
      years of data (2007 to 2011) on the prevalence of dietary supplement use, as well
      as more detailed data from the 2011 survey on the products used, the reasons for
      using supplements, and other health habits of supplement users. RESULTS: The
      prevalence of supplement use fluctuated within the range of 64% to 69% from 2007
      to 2011, and the prevalence of regular supplement use ranged from 48% to 53%,
      with no statistically significant differences from year to year. Over the 5-year
      period, the percentage of respondents who said that they regularly used a variety
      of supplements increased from 28% to 36%, and the increase from 2010 to 2011 was
      statistically significant. The percentage of respondents who said that they
      regularly used only a multivitamin, as opposed to a variety of supplements,
      declined from 24% to 17%, and the decrease from 2007 to 2008 was statistically
      significant. Detailed results from the 2011 survey confirm that supplement use
      increases with age and is higher in women than in men. Vitamin or mineral
      supplements were used by 67% of all respondents in 2011, specialty supplements by
      35%, botanicals by 23%, and sports supplements by 17%. Among supplement users,
      multivitamins were the most commonly used supplement (71%), followed by omega-3
      or fish oil (33%), calcium (32%), vitamin D (32%), and vitamin C (32%). The
      reasons most often cited for supplement use were for overall health and wellness
      (58%) and to fill nutrient gaps in the diet (42%). Supplement users were
      significantly more likely than nonusers to say that they try to eat a balanced
      diet, visit their doctor regularly, get a good night's sleep, exercise regularly,
      and maintain a healthy weight. CONCLUSIONS: Annual consumer surveys over a period
      of 5 years show that dietary supplement use is somewhat more prevalent in the
      United States than has been reported in the NHANES surveys, when occasional and
      seasonal use are taken into account, in addition to regular use. Most dietary
      supplement users take a multivitamin, and many take a variety of products. The
      primary reasons given for supplement use are for overall health and wellness or
      to fill nutrient gaps. Users of dietary supplements are more likely than nonusers
      to adopt a variety of healthy habits, indicating that supplement use is part of
      an overall approach to living healthy.

PMID- 24724777
TI  - Development of a novel anti-canine CD20 monoclonal antibody with diagnostic and
      therapeutic potential.
AB  - In humans, passive immunotherapy with anti-CD20 monoclonal antibodies (mAbs) has
      created immeasurable improvements in outcomes of patients with B-cell
      malignancies. However, the lack of comparable reagents has precluded development
      of this approach in dogs. We developed a novel anti-canine CD20 mAb designated as
      6C8. 6C8 recognized the extracellular domain of canine CD20 and showed high
      affinity binding to canine CD20 in solution, as well as in its native
      conformation on canine B-cells. The 6C8 target was expressed invariably in B-cell
      lineage cells, but not in T-cells or myeloid cells. 6C8 promoted phagocytosis of
      B-cell lymphoma cells by macrophages, but in its current framework, it did not
      induce direct cytotoxicity or complement dependent cytotoxicity. In summary, we
      have established a novel anti-canine CD20 mAb that is useful as a diagnostic tool
      to phenotype B-cells, and which could be integrated as a tool for passive
      immunotherapy to treat dogs with B-cell disorders.

PMID- 24724778
TI  - Pentostatin, cyclophosphamide and rituximab is a safe and effective treatment in
      patients with Waldenstrom's macroglobulinemia.
AB  - Waldenstrom's macroglobulinemia (WM) is an indolent lym phomaand is responsive to
      therapy regimens containing alkylating agents, purine analogs and rituximab if
      treatment becomes necessary. We initiated a multicenter phase II trial to
      determine the safety and efficacy of a regimen containing pentostatin,
      cyclophosphamide and rituximab (PER) in patients with WM. Between May 2005 and
      December 2010, 25 patients with WM were included in the study. Twenty-one
      patients received PER as first-line therapy. In these patients, 2-year
      progression-free survival was 83.6% and 2-year overall survival was 100%.
      Thirteen patients (52%) received R maintenance therapy. In these patients, the 2
      year progression-free survival was 91.67% and 2-year overall survival was 100%.
      We have provided evidence that PER is a safe and effective regimen for WM.
      Although R maintenance therapy after PER seemed to induce a better long-term
      outcome, this study was not powered to address this issue.

PMID- 24724779
TI  - Fluorescence in situ hybridization analysis does not increase detection rate for
      trisomy 8 in chronic myelomonocytic leukemia.

PMID- 24724780
TI  - The utility and limitations of (18)F-fluorodeoxyglucose positron emission
      tomography with computed tomography in patients with primary mediastinal B-cell
      lymphoma: single institution experience and literature review.
AB  - There are limited data regarding the role of (18)F-fluorodeoxyglucose positron
      emission tomography with computed tomography (FDG PET-CT) scanning in primary
      mediastinal B-cell lymphoma (PMBL). We analyzed 28 patients with PMBL treated
      with chemotherapy, of whom 25 (89%) also received rituximab and 17 (61%)
      radiotherapy. PET-CT scans were interpreted using visual analysis and a 5-point
      scale. After a median follow-up of 2.6 years, four patients relapsed and two
      died. The 2-year progression-free survival and overall survival were 86% and 94%.
      PET-CT has excellent negative predictive value (interim, 86-87%; end of
      treatment, 95%) but limited positive predictive value due to the high frequency
      of positive scans. Several patients with persistent metabolically active masses
      underwent biopsies, which showed necrosis but no lymphoma. Thus a negative PET-CT
      is an excellent predictor of subsequent outcome. However, residual metabolically
      active masses after treatment should be biopsied to confirm viable lymphoma prior
      to salvage therapy.

PMID- 24724781
TI  - Up-regulation of connexin-43 expression in bone marrow mesenchymal stem cells
      plays a crucial role in adhesion and migration of multiple myeloma cells.
AB  - Multiple myeloma (MM) cells accumulate mainly in the bone marrow (BM) and are
      closely related to the BM microenvironment. Connexin-43 (Cx43) is the main
      connexin present in bone marrow mesenchymal stem cells (BMSCs). We found that
      normal BMSCs expressed a lower level of Cx43 than those derived from patients
      with MM. Cx43 expression in BMSCs was up-regulated at both the gene and protein
      level, and gap junction-mediated intercellular communication was improved in
      BMSCs after co-culture with RPMI 8226 cells. The gap junction blocker 18alpha
      glycyrrhetinic acid (18alpha-GA) inhibited the adherence of MM cells to BMSCs.
      Treatment with 18alpha-GA decreased stromal cell-derived factor-1alpha (SDF
      1alpha) secretion by BMSCs and inhibited the migration of MM cells induced by
      BMSCs. These results suggest that alteration of Cx43 expression in BMSCs is
      involved in the interactions of MM cells with the BM environment and plays a
      crucial role in the adhesion and migration of MM cells.

PMID- 24724782
TI  - Acute myeloid leukemia in patients older than 75: prognostic impact of FLT3-ITD
      and NPM1 mutations.
AB  - The benefit associated with chemotherapy in older patients with acute myeloid
      leukemia (AML) is debated. The prognostic impact of molecular mutations in these
      patients is unknown. We identified 79 patients with AML aged 75 years or over.
      Forty-two received chemotherapy and 37 supportive care only. In intensively
      treated patients, overall survival was longer (p < 0.001). Achieving complete
      remission was associated with longer survival (p < 0.001). NPM1 mutations tended
      to be associated with a higher complete remission rate (p = 0.12). In
      multivariate analysis, FLT3-ITD was associated with poorer survival (p = 0.049).
      Patients harboring FLT3-ITD and no NPM1 mutation had a poorer prognosis than
      others (p = 0.02). Intensive treatments can benefit a portion of elderly
      patients. FLT3-ITD and NPM1 mutational status might be useful for prognosis
      stratification.

PMID- 24724783
TI  - Low-dose homoharringtonine and cytarabine in combination with granulocyte colony
      stimulating factor for elderly patients with de novo acute myeloid leukemia.
AB  - The treatment of young patient with acute myeloid leukemia (AML) has improved
      dramatically during the past several decades. However, management of elderly
      patients with AML still remains a challenge. A total of 56 elderly patients with
      de novo AML were treated with homoharringtonine and cytarabine in combination
      with granulocyte colony-stimulating factor (HCG). The overall response rate was
      75% (60.7%% complete response [CR] and 14.3% partial response). Fourteen (25%) of
      the 56 patients showed no response. A higher CR rate was observed in patients
      aged < 70 years, with better-risk or intermediate-risk karyotype and with NPM1
      mutations. To the date of the last follow-up, the median overall survival (OS)
      was 12.0+/-1.7 months. There were significant correlations of OS with age,
      initial karyotype, performance status and gene mutations (NPM1,FLT-ITD and
      DNMT3A) at diagnosis. The early death rate was 7.1%. Hematologic toxicity was
      well tolerated; and severe non-hematologic toxicity was not observed.

PMID- 24724784
TI  - Absence of miR-142 mutation in Chinese patients with acute myeloid leukemia.

PMID- 24724785
TI  - Deleterious effects of non-branded versions of imatinib used for the treatment of
      patients with chronic myeloid leukemia in chronic phase: a case series on an
      escalating issue impacting patient safety.
AB  - Glivec (imatinib mesylate) has changed the natural history of chronic-phase
      chronic myeloid leukemia (CML-CP), transforming it into a long-term and
      manageable disease. At our institution, we treat over 100 patients with CML-CP
      per year, typically with first-line imatinib therapy. Recently, several
      healthcare systems and insurance providers have substituted non-branded versions
      of imatinib that have not demonstrated efficacy or safety comparable to that of
      imatinib. Here, we analyzed a series of 12 patients who were exposed to non
      branded versions of imatinib. Following the switch from branded imatinib to non
      branded imatinib, 5/8 patients (63%) experienced treatment failure and 6/8 (75%)
      experienced severe and recurrent adverse events. All four patients treated with
      first-line non-branded imatinib therapy experienced resistance or a suboptimal
      response, and 3/4 (75%) also experienced intolerance. Overall in this small
      patient cohort, all 12 patients treated with non-branded imatinib therapies
      failed to meet common treatment milestones and/or suffered recurrent and severe
      adverse events.

PMID- 24724786
TI  - Transfusion complications in thalassemias.

PMID- 24724787
TI  - Retinopathy of prematurity and transfusion practice.

PMID- 24724788
TI  - Transfusion medicine illustrated. Catastrophic basilar artery leukostasis in the
      setting of acute myeloid leukemia.

PMID- 24724789
TI  - Hemophilia treatment and the AIDS tragedy: closing the circle.

PMID- 24724790
TI  - Wrong blood in tube error: first study on donor blood samples.

PMID- 24724791
TI  - Antibodies titration for immunized pregnant women: conventional tube test or gel
      microcolumn assay.

PMID- 24724792
TI  - Blood and bombs: blood use after the Boston Marathon bombing of April 15, 2013.

PMID- 24724797
TI  - Copper(I)-catalyzed nucleophilic addition of ynamides to acyl chlorides and
      activated N-heterocycles.
AB  - The addition of ynamides to acyl chlorides and N-heterocycles activated in situ
      with ethyl chloroformate has been accomplished at room temperature using copper
      iodide as catalyst. This economical and practical carbon-carbon bond formation
      provides convenient access to a variety of 3-aminoynones from aliphatic and
      aromatic acyl chlorides in up to 99% yield. The addition to pyridines and
      quinolines occurs under almost identical conditions and proceeds with good to
      high regioselectivity, producing the corresponding 1,2-dihydro-N-heterocycles in
      up to 95% yield. 

PMID- 24724793
TI  - Immunosuppressive and anti-inflammatory properties of engineered nanomaterials.
AB  - Nanoparticle interactions with various components of the immune system are
      determined by their physicochemical properties such as size, charge,
      hydrophobicity and shape. Nanoparticles can be engineered to either specifically
      target the immune system or to avoid immune recognition. Nevertheless,
      identifying their unintended impacts on the immune system and understanding the
      mechanisms of such accidental effects are essential for establishing a
      nanoparticle's safety profile. While immunostimulatory properties have been
      reviewed before, little attention in the literature has been given to
      immunosuppressive and anti-inflammatory properties. The purpose of this review is
      to fill this gap. We will discuss intended immunosuppression achieved by either
      nanoparticle engineering, or the use of nanoparticles to carry immunosuppressive
      or anti-inflammatory drugs. We will also review unintended immunosuppressive
      properties of nanoparticles per se and consider how such properties could be
      either beneficial or adverse.

PMID- 24724798
TI  - Radiofrequency ablation of drug refractory ventricular tachycardia related to
      cocaine use: a feasibility, safety, and efficacy study.
AB  - BACKGROUND: Cocaine use is a known but rare cause of cardiac arrhythmias.
      Ventricular arrhythmias related to cocaine may not respond to antiarrhythmic
      drugs and may need treatment with radiofrequency ablation. OBJECTIVES: We
      describe the clinical and electrophysiological characteristics of cocaine-related
      ventricular tachycardia (VT) from a multicenter registry. METHODS: Subjects
      presenting with VT related to cocaine use and being considered for radiofrequency
      ablation have been included in the study. Patients who were refractory to maximal
      medical therapy underwent radiofrequency ablation of the VT. Clinical, procedural
      variables, efficacy, and safety outcomes were assessed. RESULTS: A total of 14
      subjects met study criteria (age 44 +/- 13, range 18- to 68-year-old with 79%
      male, 71% Caucasian). MRI showed evidence of scar only in 43% of patients (6/14).
      The mechanism of VT was focal in 50% (n = 7) and scar related reentry in 50% (n =
      7) based on 3D mapping. The mean VT cycle length was 429 +/- 96 milliseconds. The
      site of origin was epicardial in 16% (3/18) of VTs. Most clinical VTs were
      hemodynamically stable (75%). Mean ejection fraction at the time of admission was
      44 +/- 14%. Duration of procedure was 289 +/- 50 minutes. One subject developed
      pericardial tamponade requiring drainage. At 18 +/- 11 months follow-up, freedom
      from arrhythmia was seen in 86% (1 case lost to follow-up and 2 died).
      CONCLUSION: Radiofrequency ablation is not only feasible but also safe and
      effective in patients who have drug refractory VT related to chronic cocaine use.

PMID- 24724800
TI  - Perceived behavioural control, subjective norms, attitudes and intention to use
      condom: a longitudinal cross-lagged design.
AB  - Based on the Theory of Planned Behaviour (TPB), the purpose of this investigation
      was to examine the directionality of the association among condom use, intention,
      attitudes, subjective norms and perceived behavioural control. The present study
      investigated the nature of these relationships using a longitudinal cross-lagged
      design applied to data from a cohort of 958 randomly selected Italian adults.
      Using structural equation modelling, two cross-lagged panel analyses revealed
      reciprocal relationships between intention and attitudes and between intention
      and condom use. Contrary to expectations, baseline subjective norms and perceived
      behavioural control did not predict subsequent intention to use condom when
      controlled for the autoregressive effect of intention at T1 on the same variable
      at T2. Also, perceived behavioural control at T1 did not influence condom use at
      T2 after controlling for the effect of baseline intention. The possibility of
      reciprocity was also tested for all relations and significant results were found.
      The moderation effect of perceived behavioural control on the relationship
      between intention and condom use was not significant. The differences in age,
      gender and partnership status were taken into account in the analyses. 

PMID- 24724799
TI  - Structure and catalytic regulatory function of ubiquitin specific protease 11 N
      terminal and ubiquitin-like domains.
AB  - The ubiquitin specific protease 11 (USP11) is implicated in DNA repair, viral RNA
      replication, and TGFbeta signaling. We report the first characterization of the
      USP11 domain architecture and its role in regulating the enzymatic activity.
      USP11 consists of an N-terminal "domain present in USPs" (DUSP) and "ubiquitin
      like" (UBL) domain, together referred to as DU domains, and the catalytic domain
      harboring a second UBL domain. Crystal structures of the DU domains show a tandem
      arrangement with a shortened beta-hairpin at the two-domain interface and altered
      surface characteristics compared to the homologues USP4 and USP15. A conserved
      VEVY motif is a signature feature at the two-domain interface that shapes a
      potential protein interaction site. Small angle X-ray scattering and gel
      filtration experiments are consistent with the USP11DU domains and full-length
      USP11 being monomeric. Unexpectedly, we reveal, through kinetic assays of a
      series of deletion mutants, that the catalytic activity of USP11 is not regulated
      through intramolecular autoinhibition or activation by the N-terminal DU or UBL
      domains. Moreover, ubiquitin chain cleavage assays with all eight linkages reveal
      a preference for Lys(63)-, Lys(6)-, Lys(33)-, and Lys(11)-linked chains over
      Lys(27)-, Lys(29)-, and Lys(48)-linked and linear chains consistent with USP11's
      function in DNA repair pathways that is mediated by the protease domain. Our data
      support a model whereby USP11 domains outside the catalytic core domain serve as
      protein interaction or trafficking modules rather than a direct regulatory
      function of the proteolytic activity. This highlights the diversity of USPs in
      substrate recognition and regulation of ubiquitin deconjugation. 

PMID- 24724801
TI  - Two cases of tinea ciliaris with blepharitis due to Microsporum audouinii and
      Trichophyton verrucosum and review of the literature.
AB  - Dermatophytes are rarely taken into account among the causes of blepharitis. In
      our report, we describe a 69-year-old man and a 40-year-old woman with chronic
      blepharitis for 10 years and 4 years respectively, in whom we examined the scales
      and pulled eyelashes on direct microscopy and isolated Microsporum audouinii and
      Trichophyton verrrucosum in the culture. We emphasise that dermatophytes may play
      a role in the etiopathogenesis of chronic blepharitis. In chronic, treatment
      resistance blepharitis fungal infections may be considered as possible cause.

PMID- 24724802
TI  - Challenging the other: exploring the role of opponent gender in digital game
      competition for female players.
AB  - Abstract The present study investigated the effect of opponent gender on the game
      experience of female players. Concretely, it looked into skill perception and
      player emotions of women in same gender and cross-gender game competition. We set
      up a 2*2*2 (male vs. female opponent*low vs. high competitive women*lost vs. won
      game) experimental design in which women were instructed to play against a
      proclaimed male and female competitor. Unknowingly, however, participants played
      against an AI, which was configured to produce a winning and a losing condition
      for each opponent by manipulating difficulty. Results indicated that opponent
      gender only had an effect on perceived stress, which was higher with male
      opponents. Moreover, players evaluated their own gaming skills as lower and the
      skills of presumed male opponents as higher when they thought they were playing
      against men. Importantly, our results also showed that the above described
      pattern for self-perceived skills and perceived opponent skills was modulated by
      trait competitiveness with a larger effect size for low competitive women.
      Overall, this study illustrates that gender dynamics affect the play experience
      of women in cross-gender gaming competition. Implications and suggestions for
      future research are discussed. 

PMID- 24724803
TI  - Stereoselective synthesis of 2alpha-Chloropicropodophyllotoxins and insecticidal
      activity of their esters against oriental armyworm, Mythimna separata walker.
AB  - As part of ongoing efforts to discover new natural-product-based insecticidal
      agents, in the present study, an efficient method for the stereoselective alpha
      chlorination at the C-2 position of 2'(2',6')-(di)halogenopodophyllotoxin
      derivatives was first developed. Subsequently, a series of novel esters of 2alpha
      chloro-2'(2',6')-(di)halogenopicropodophyllotoxin with modified C, D, and E rings
      of podophyllotoxin were smoothly obtained. Finally, all of the title compounds
      were tested against the pre-third-instar larvae of oriental armyworm (Mythimna
      separata Walker) at 1 mg/mL. It was found that besides their 2'-halogen
      substituted E ring, the stereoselective alpha-chlorination at the C-2 position of
      2'(2',6')-(di)halogenopodophyllotoxins was also related to the chlorination
      reagents. Especially 2alpha-chloro-4alpha-(benzoyl)oxy-2'
      chloropicropodophyllotoxin (6e) and 2alpha-chloro-4alpha-(2-chlorophenylacyl)oxy
      2'-bromopicropodophyllotoxin (8f) showed the most potent insecticidal activities,
      with final mortality rates of >60%. For 4alpha-(alkylacyl)oxy derivatives of
      2alpha-chloro-2'(2',6')-(di)halogenopicropodophyllotoxin, the effect of the
      length of their side chain at the C-4 position of podophyllotoxin skeleton on the
      insecticidal activity was not very obvious. For 4alpha-(arylacyl)oxy derivatives
      of 2alpha-chloro-2'-chloro/bromopicropodophyllotoxin, an electronic effect of the
      substituents on their phenyl ring at the C-4 position of podophyllotoxin skeleton
      on the insecticidal activity was observed. 

PMID- 24724804
TI  - Continuous subcutaneous insulin infusion (CSII) versus multiple daily injections
      (MDI) of rapid-acting insulin analogues and detemir in type 1 diabetic (T1D)
      pregnant women.
AB  - OBJECTIVE: To compare glycemic control, maternal-neonatal outcomes and fetal fat
      body mass growth of type 1 diabetic pregnant women treated with continuous
      subcutaneous insulin infusion (CSII) or multiple daily injections (MDI) with the
      long-acting insulin analogue detemir as basal insulin. METHODS: Retrospective
      study of 53 women, attending the Unit of Prenatal Medicine of Careggi University
      Hospital, Florence, from 2009 to 2012: 35 treated with CSII, 18 with MDI-detemir.
      Each woman performed daily blood glucose self-monitoring, had an individualized
      nutritional therapy, weekly prenatal visits and ultrasound scans (US) according
      to the Tuscan guidelines. US were also performed every two weeks from 28 to 38
      weeks of gestation to assess fetal fat body mass growth. Student's t-test and Chi
      square test were performed to compare the groups' results. RESULTS: No
      significant differences were observed in metabolic control, in any maternal and
      neonatal outcome nor fetal fat body mass growth for either group. The MDI group
      needed higher daily doses of insulin (MDI: 1.00 +/- 0.32 UI/kg versus CSII: 0.75
      +/- 0.29 UI/kg, p = 0.007) to reach results comparable to the CSII group.
      CONCLUSIONS: MDI therapy with detemir is a safe and effective alternative, with a
      good benefit-cost ratio compared to insulin pumps.

PMID- 24724805
TI  - A high-fat maternal diet decreases adiponectin receptor-1 expression in
      offspring.
AB  - In early life, over-nutrition may increase the risk of insulin resistance in the
      adult stage. Adiponectin and its receptor may play a key role in this process.
      This study aimed to identify the effect of a high-fat (HF) maternal diet on
      metabolic parameters and muscle adiponectin signaling in young adult offspring.
      We found that offspring born to dams fed HF chow (HF; 31% of calories from fat)
      had elevated body and adipose tissue weight and higher serum glucose levels after
      glucose challenge at three weeks (W3) and eight weeks (W8) of age. Offspring
      exposed to a HF diet also had higher serum adiponectin levels at W3 compared to
      controls. However, adiponectin levels were significantly decreased compared to
      controls by W8. Adiponectin receptor 1 mRNA expression in skeletal muscle was
      decreased in the HF group at W3 and W8, and there was no difference between the
      two groups in adiponectin receptor 2 expression. Furthermore, glucose transporter
      4 mRNA and protein expression was decreased in the skeletal muscle of the HF
      group at W3 and W8. Our results suggest that a HF maternal diet decreases
      adiponectin receptor 1 expression in the offspring, which could contribute to
      reduced sensitivity to adiponectin and to adverse nutritional programing
      outcomes.

PMID- 24724806
TI  - Heterocyclic aromatic hydrocarbons show estrogenic activity upon metabolization
      in a recombinant transactivation assay.
AB  - Heterocyclic aromatic hydrocarbons (hetero-PAHs) are increasingly studied at
      contaminated sites; especially at former industrial facilities where coal tar-oil
      was handled, e.g., wood treatment plants, high concentrations of hetero-PAHs are
      frequently detected in groundwater plumes. In previous studies, fractions of
      groundwater with high estrogenic activity contained hetero-PAHs and their
      hydroxylated metabolites. To evaluate this preliminary evidence, selected hetero
      PAHs were screened for their estrogenic activity in lyticase yeast estrogen
      screen (LYES) and ER CALUX. All tested substances were inactive in the LYES.
      Hetero-PAHs such as acridine, xanthene, indole, 2-methylbenzofuran, 2,3
      dimethylbenzofuran, dibenzofuran, dibenzothiophene, quinoline, and 6
      methylquinoline were positive in the ER CALUX, with estradiol equivalence factors
      (EEFs) from 2.85 * 10(-7) to 3.18 * 10(-5). The EEF values of these substances
      were comparable to those of other xenoestrogens (e.g., alkylphenols or bisphenol
      A) that are sometimes found in surface water. Chemical analyses revealed that
      T47Dluc cells could metabolize most of the substances. Among the metabolites
      (tentatively) identified by liquid chromatography-tandem mass spectrometry (LC
      MS/MS) were hydroxides and their keto tautomers, sulfates, sulfoxides, and N
      oxides. Because of their high concentrations measured in groundwater, we conclude
      that hetero-PAHs and metabolites may be a potential risk and should be the
      subject of further research. 

PMID- 24724807
TI  - Effects of folic acid on renal endothelial function in patients with diabetic
      nephropathy: results from a randomized trial.
AB  - Endothelial dysfunction has been shown to promote podocyte injury and albuminuria
      in diabetes, highlighting the importance of the interaction between renal
      endothelial cells and podocytes. Folic acid (FA) improves nitric oxide synthase
      (NOS) function and reduces progression of diabetic nephropathy in animal models.
      We tested whether high-dose FA treatment improves renal endothelial function and
      albuminuria in human subjects with incipient diabetic nephropathy. Following a
      double-blind, randomized, cross-over design, 28 patients with Type 2 diabetes and
      albuminuria were allocated to 4 weeks' treatment with placebo and high-dose FA (5
      mg/day). Renal nitric oxide (NO) production determined as the response of renal
      plasma flow (RPF) to NOS inhibition with NG-monomethyl-L-arginine (L-NMMA) (4.25
      mg/kg intravenously), renal oxidant stress as response of RPF to vitamin C
      infusion (3 mg/kg) and albuminuria were determined after each treatment phase.
      Neither the reduction in RPF to L-NMMA nor the increase in RPF to vitamin C
      infusion differed between treatment phases (DeltaRPF to L-NMMA: -74+/-71 ml/min
      per m2 during placebo compared with -63+/-56 ml/min per m2 during FA, P=0.57;
      DeltaRPF to vitamin C: +93+/-118 ml/min per m2 compared with +94+/-108 ml/min per
      m2; P=0.70). In line with the lack of effect on the renal endothelium,
      albuminuria was not affected by FA treatment (110+/-179 mg/day during placebo
      compared with 87+/-146 mg/day during FA; P=0.12). High-dose FA treatment does not
      improve renal endothelial function and fails to reduce albuminuria in human
      subjects with diabetic nephropathy. Novel treatment options for oxidant stress
      and endothelial dysfunction in patients with diabetes are urgently needed.

PMID- 24724809
TI  - Constructing robust liquid marbles for miniaturized synthesis of graphene/Ag
      nanocomposite.
AB  - Miniaturized synthesis is attracting much attention due to many potential
      applications; a challenge remains in exploring versatile microreactors capable of
      producing pure products. In this study, we reported a kind of thermally robust
      liquid marbles and their application for miniaturized synthesis of graphene/Ag
      nanocomposite. The liquid marbles were constructed by using superhydrophobic
      Fe3O4/C microsheets as encapsulating agents. Results revealed that the morphology
      of the encapsulating agent as well as the humidity of atmosphere strongly
      affected the robustness of liquid marbles at elevated temperature. The resulting
      graphene/Ag nanocomposite showed one of the best catalytic characteristics for 4
      nitroaniline reduction among the reported catalysts. The findings of this study
      not only offer an alternative insight into the stability of liquid marbles at
      elevated temperature but also provide a facile strategy for miniaturized
      synthesis.

PMID- 24724810
TI  - Meta-Analytic Approaches for Multistressor Dose-Response Function Development:
      Strengths, Limitations, and Case Studies.
AB  - For many policy analyses, including but not limited to cumulative risk
      assessments, it is important to characterize the individual and joint health
      effects of multiple stressors. With an increasing focus on psychosocial and other
      nonchemical stressors, this often includes epidemiological meta-analysis. Meta
      analysis has limitations if epidemiological studies do not include all of the
      stressors of interest or do not provide multivariable outputs in a format
      necessary for risk assessment. Given these limitations, novel analytical methods
      are often needed to synthesize the published literature or to build upon
      available evidence. In this article, we discuss three recent case studies that
      highlight the strengths and limitations of meta-analytic approaches and other
      research synthesis techniques for human health risk assessment applications.
      First, a literature-based meta-analysis within a risk assessment context informed
      the design of a new epidemiological investigation of the differential toxicity of
      fine particulate matter constituents. Second, a literature synthesis for an
      effects-based cumulative risk assessment of hypertension risk factors led to a
      decision to develop new epidemiological associations using structural equation
      modeling. Third, discrete event simulation modeling was used to simulate the
      impact of changes in the built environment on environmental exposures and
      associated asthma outcomes, linking literature meta-analyses for key associations
      with a simulation model to synthesize all of the model components. These case
      studies emphasize the importance of conducting epidemiology with a risk
      assessment application in mind, the need for interdisciplinary collaboration, and
      the value of advanced analytical methods to synthesize epidemiological and other
      evidence for risk assessment applications. 

PMID- 24724811
TI  - Impaired circulation in the thickened choroid of a patient with serpiginous
      choroiditis.

PMID- 24724812
TI  - Perceptions and health beliefs of Greek nursing students about breast self
      examination: A descriptive study.
AB  - Breast self-examination is a screening option for young women. Among students,
      knowledge about breast self-examination ranges from insufficient to average. This
      descriptive study was planned in order to determine the health beliefs and
      perceptions of nursing students regarding breast self-examinations. We recruited
      538 nursing students in a single Higher Technological Educational Institute in
      Greece. Data were collected using the Champion's Health Belief Model Scale.
      Parametric tests were used in the data analysis. We found significant differences
      in the results of the subscales of Champion's Health Belief Model Scale on
      comparing people with respect to nationality, previous education about breast
      self-examination, smoking status and semester in which they were studying. The
      'confidence' subscale was positively associated with the frequency of breast self
      examination. The results of the present study demonstrated that nursing students
      have knowledge about breast-self examination but inadequate practice. 

PMID- 24724813
TI  - Changes in exercise capacity, quality of life and fatigue in cancer patients
      during an intervention.
AB  - The study explored the interdependence of changes in oxygen uptake, quality of
      life and cancer-related side-effect fatigue during a 4-month exercise
      intervention. Participants were during adjuvant (curative) or palliative therapy
      and post-adjuvant therapy (finished within the previous 12 months). Aerobic
      exercise capacity (VO2 peak), quality of life and fatigue symptom (EORTC QLQ-C30)
      were obtained in 101 cancer patients (30-77 years). After initial examination,
      patients participated in supervised and/or home-based training interventions.
      Patients were re-examined after 16-20 weeks and stratified into 3 subgroups
      (terciles) with respect to the absolute change in VO2 peak. The ANCOVA, with
      significant covariate effect for pretest fatigue score (F(5,101) = 8.150, P <
      0.001), indicated significant differences between groups in outcome measures (P <
      0.001). Based on the absolute change of VO2 peak (1.9 +/- 1.7; 1.8 +/- 0.8; 5.7
      +/- 2.8 ml/kg/min) there were significant differences in the quality of life
      improvement (17.2 +/- 15.1 vs. 4.8 +/- 22.0 points, P < 0.05) and cancer-related
      fatigue reduction (-6.1 +/- 30.7; -11.5 +/- 20.9; -21.2 +/- 21.4 points) between
      upper and lower tercile. The findings point towards a relationship of exercise
      capacity enhancement, quality of life improvement and fatigue symptom reduction
      during and shortly after cancer treatment. 

PMID- 24724814
TI  - Polarization tailored light driven directional optical nanobeacon.
AB  - We experimentally demonstrate all-optical control of the emission directivity of
      a dipole-like nanoparticle with spinning dipole moment sitting on the interface
      to an optical denser medium. The particle itself is excited by a tightly focused
      polarization tailored light beam under normal incidence. The position dependent
      local polarization of the focal field allows for tuning the dipole moment via
      careful positioning of the particle relative to the beam axis. As an application
      of this scheme, we investigate the polarization dependent coupling to a planar
      two-dimensional dielectric waveguide. 

PMID- 24724815
TI  - Suppression of aggressive strains of 'Candidatus phytoplasma mali' by mild
      strains in Catharanthus roseus and Nicotiana occidentalis and indication of
      similar action in apple trees.
AB  - To study antagonistic interactions of 'Candidatus Phytoplasma mali' strains,
      graft inoculation of Catharanthus roseus and Nicotiana occidentalis was performed
      with mild strains 1/93Vin and 1/93Tab as suppressors and three aggressive strains
      as challengers. Inoculation of the suppressors was carried out in either the
      cross-protection modus prior to grafting of the challengers or by co-inoculating
      suppressors and challengers. Monitoring using multiplex real-time polymerase
      chain reaction assays revealed that, in long-term cross-protection trials with C.
      roseus, suppressor 1/93Vin was present in all root and randomly collected stem
      samples over the entire observation period. In contrast, the challengers were
      never detected in such stem samples and rarely in the roots. Following
      simultaneous inoculation, the suppressor successively colonized all stem and root
      regions whereas detection of challenger AT steadily decreased. However, this
      strain remained detectable in up to 13 and 27% of stem and root samples,
      respectively. The cross-protection trials with N. occidentalis yielded results
      similar to that of the cross-protection experiments with C. roseus. Comparison of
      the symptomatology of infected apple trees with the presence of putatively
      suppressive strains indicated that suppression of severe strains also occurs in
      apple. Phylogenetic analysis using a variable fragment of AAA+ ATPase gene AP460
      of 'Ca. P. mali' revealed that suppressors 1/93Vin and 1/93Tab, together with
      several other mild strains maintained in apple, cluster distantly from obviously
      nonsuppressive strains that were predominantly highly virulent.

PMID- 24724816
TI  - Responses of tomato genotypes to avirulent and Mi-virulent Meloidogyne javanica
      isolates occurring in Israel.
AB  - The behavior of naturally virulent Meloidogyne isolates toward the tomato
      resistance gene Mi in major tomato-growing areas in Israel was studied for the
      first time. Virulence of seven selected isolates was confirmed over three
      successive generations on resistant (Mi-carrying) and susceptible (non-Mi
      carrying) tomato cultivars. Diagnostic markers verified the predominance of
      Meloidogyne javanica among virulent isolates selected on resistant tomato
      cultivars or rootstocks. To better understand the determinants of nematode
      selection on Mi-carrying plants, reproduction of Mi-avirulent and virulent
      isolates Mjav1 and Mjv2, respectively, measured as eggs per gram of root, on non
      Mi-carrying, heterozygous (Mi/mi) and homozygous (Mi/Mi) genotypes was evaluated.
      Although no reproduction of Mjav1 was observed on Mi/Mi genotypes, some
      reproduction was consistently observed on Mi/mi plants; reproduction of Mjv2 on
      the homozygous and heterozygous genotypes was similar to that on susceptible
      cultivars, suggesting a limited quantitative effect of the Mi gene. Histological
      examination of giant cells induced by Mi-virulent versus avirulent isolates
      confirmed the high virulence of Mjv2 on Mi/mi and Mi/Mi genotypes, allowing the
      formation of well-developed giant-cell systems despite the Mi gene. Analysis of
      the plant defense response in tomato Mi/Mi, Mi/mi, and mi/mi genotypes to both
      avirulent and virulent isolates was investigated by quantitative real-time
      polymerase chain reaction. Although the jasmonate (JA)-signaling pathway was
      clearly upregulated by avirulent and virulent isolates on the susceptible (not
      carrying Mi) and heterozygous (Mi/mi) plants, no change in signaling was observed
      in the homozygous (Mi/Mi) resistant line following incompatible interaction with
      the avirulent isolate. Thus, similar to infection promoted by the avirulent
      isolate on the susceptible genotype, the Mi-virulent isolate induced the JA
      dependent pathway, which might promote tomato susceptibility during the
      compatible interaction with the homozygous (Mi/Mi) resistant line. These results
      have important consequences for the management of Mi resistance genes for
      ensuring sustainable tomato farming.

PMID- 24724818
TI  - Immune reconstitution inflammatory syndrome-Unmasking endophthalmic,
      lymphadenopathic, and neuromeningeal cryptococcosis in an HIV-infected patient
      starting highly active antiretroviral therapy.

PMID- 24724817
TI  - Engineering cellular response using nanopatterned bulk metallic glass.
AB  - Nanopatterning of biomaterials is rapidly emerging as a tool to engineer cell
      function. Bulk metallic glasses (BMGs), a class of biocompatible materials, are
      uniquely suited to study nanopattern-cell interactions as they allow for
      versatile fabrication of nanopatterns through thermoplastic forming. Work
      presented here employs nanopatterned BMG substrates to explore detection of
      nanopattern feature sizes by various cell types, including cells that are
      associated with foreign body response, pathology, and tissue repair. Fibroblasts
      decreased in cell area as the nanopattern feature size increased, and fibroblasts
      could detect nanopatterns as small as 55 nm in size. Macrophages failed to detect
      nanopatterns of 150 nm or smaller in size, but responded to a feature size of 200
      nm, resulting in larger and more elongated cell morphology. Endothelial cells
      responded to nanopatterns of 100 nm or larger in size by a significant decrease
      in cell size and elongation. On the basis of these observations, nondimensional
      analysis was employed to correlate cellular morphology and substrate
      nanotopography. Analysis of the molecular pathways that induce cytoskeletal
      remodeling, in conjunction with quantifying cell traction forces with nanoscale
      precision using a unique FIB-SEM technique, enabled the characterization of
      underlying biomechanical cues. Nanopatterns altered serum protein adsorption and
      effective substrate stiffness, leading to changes in focal adhesion density and
      compromised activation of Rho-A GTPase in fibroblasts. As a consequence, cells
      displayed restricted cell spreading and decreased collagen production. These
      observations suggest that topography on the nanoscale can be designed to engineer
      cellular responses to biomaterials. 

PMID- 24724819
TI  - Predictors of hippocampal atrophy in critically ill patients.
AB  - BACKGROUND AND PURPOSE: Hippocampal atrophy is presumably one morphological sign
      of critical illness encephalopathy; however, predictors have not yet been
      determined. METHODS: The data for this report derived from patients treated at
      the intensive care units (ICUs) of the University Hospital in Bonn in the years
      2004-2006. These patients underwent structural magnetic resonance imaging 6-24
      months after discharge. Volumes (intracranial, whole brain, white matter, grey
      matter, cerebral spinal fluid, bilateral hippocampus) were compared with healthy
      controls. Pro-inflammatory parameters and ICU scoring systems were explored in
      conjunction with brain volumes. Cut-scores were defined to differentiate patients
      with high from those with low inflammatory response. RESULTS: Hippocampal and
      white matter volume were reduced in critically ill patients compared with healthy
      controls. Procalcitonin showed a very strong correlation (r = -0.903, P = 0.01)
      and interleukin-6 a moderate correlation (r = -0.538, P = 0.031) with hippocampal
      volume, but not with other brain volumes. C-reactive protein was linked to grey
      matter volume. There was no correlation with systemic inflammatory response
      syndrome criteria (body temperature, heart rate, respiratory rate, white blood
      cell count) or for hippocampal or whole brain volume. Furthermore, parameters
      representing severity of disease (APACHE II score, SOFA score, duration of stay
      and duration of mechanical ventilation) were not associated with hippocampal or
      other brain volumes. CONCLUSIONS: This analysis suggests that high levels of
      procalcitonin and interleukin-6 in the blood serum of critically ill patients are
      associated with a high likelihood of hippocampal atrophy irrespective of the
      severity of disease measured by ICU scoring systems and other inflammatory
      parameters.

PMID- 24724820
TI  - Experimentally decoupling reproductive investment from energy storage to test the
      functional basis of a life-history trade-off.
AB  - The ubiquitous life-history trade-off between reproduction and survival has long
      been hypothesized to reflect underlying energy-allocation trade-offs between
      reproductive investment and processes related to self-maintenance. Although
      recent work has questioned whether energy-allocation models provide sufficient
      explanations for the survival cost of reproduction, direct tests of this
      hypothesis are rare, especially in wild populations. This hypothesis was tested
      in a wild population of brown anole lizards (Anolis sagrei) using a two-step
      experiment. First, stepwise variation in reproductive investment was created
      using unilateral and bilateral ovariectomy (OVX) along with intact (SHAM)
      control. Next, this manipulation was decoupled from its downstream effects on
      energy storage by surgically ablating the abdominal fat stores from half of the
      females in each reproductive treatment. As predicted, unilateral OVX
      (intermediate reproductive investment) induced levels of growth, body condition,
      fat storage and breeding-season survival that were intermediate between the high
      levels of bilateral OVX (no reproductive investment) and the low levels of SHAM
      (full reproductive investment). Ablation of abdominal fat bodies had a strong and
      persistent effect on energy stores, but it did not influence post-breeding
      survival in any of the three reproductive treatments. This suggests that the
      energetic savings of reduced reproductive investment do not directly enhance post
      breeding survival, with the caveat that only one aspect of energy storage was
      manipulated and OVX itself had no overall effect on post-breeding survival. This
      study supports the emerging view that simple energy-allocation models may often
      be insufficient as explanations for the life-history trade-off between
      reproduction and survival. 

PMID- 24724821
TI  - Magnetic resonance imaging, computed tomography, and gross anatomy of the canine
      tarsus.
AB  - OBJECTIVES: To describe the normal anatomy of the soft tissues of the canine
      tarsus as identified on computed tomography (CT) and magnetic resonance imaging
      (MRI) and to evaluate specific MRI sequences and planes for observing structures
      of diagnostic interest. STUDY DESIGN: Prospective descriptive study. ANIMALS:
      Canine cadavers (n = 3). METHODS: A frozen cadaver pelvic limb was used to trial
      multiple MRI sequences using a 1.5 T superconducting magnet and preferred
      sequences were selected. Radiographs of 6 canine cadaver pelvic limbs confirmed
      the tarsi were radiographically normal. A 16-slice CT scanner was used to obtain
      1 mm contiguous slices through the tarsi. T1-weighted, proton density with fat
      suppression (PD FS) and T2-weighted MRI sequences were obtained in the sagittal
      plane, T1-weighted, and PD FS sequences in the dorsal plane and PD FS sequences
      in the transverse plane. The limbs were frozen for one month and sliced into 4-5
      mm thick frozen sections. Anatomic sections were photographed and visually
      correlated to CT and MR images. RESULTS: Most soft tissue structures were easiest
      to identify on the transverse MRI sections with cross reference to either the
      sagittal or dorsal plane. Bony structures were easily identified on all CT, MR,
      and gross sections. CONCLUSIONS: The anatomy of the canine tarsus can be readily
      identified on MR imaging.

PMID- 24724822
TI  - Changing trends in blood transfusion: an analysis of 244,013 hospitalizations.
AB  - BACKGROUND: Identifying recipients of blood transfusion and the trends in
      transfusion are needed to properly identify and target clinical services in need
      of patient blood management strategies. We determined the proportion of
      admissions to each clinical service that received blood, the mean number of units
      utilized, and the 5-year trends in utilization. STUDY DESIGN AND METHODS: We used
      a large administrative database, a repository for three campuses of one
      university-affiliated hospital, and included all adults that were hospitalized
      from November 1, 2006, to June 2012. The data were analyzed as the proportion of
      admissions transfused and the mean number units transfused per admission.
      RESULTS: Of 244,013 hospitalizations, 38,265 received at least one transfusion
      (29,165 for red blood cells [RBCs], 6760 for plasma, and 5795 for platelets
      [PLTs]). Although there has been a gradual decrease in the mean number of RBCs
      transfused (percent change, -9.8%; p = 0.002), an increase in the proportion of
      admissions receiving RBCs (17.2% increase, p < 0.0001) and PLTs (31.5% increase,
      p < 0.0001) was apparent while there has been a decrease in the proportion of
      admissions receiving plasma (23.9% decrease, p < 0.0001). Eight percent of
      cardiology admissions received RBCs, and the highest mean RBC utilization per
      admission, aside from the stem cell transplantation service, occurred in
      cardiology and critical care hospitalizations (mean, 4.7 units/hospitalization).
      CONCLUSION: Although there has been a reduction in the mean RBC units used, there
      has been an increase in the proportion of hospitalizations transfused. A better
      understanding of the indications for transfusion is required to facilitate the
      development of targeted blood conservation strategies.

PMID- 24724823
TI  - Antibiotic consumption and antibiotic stewardship in Swedish hospitals.
AB  - BACKGROUND: The aim of this paper was to describe and analyze the effect of
      antibiotic policy changes on antibiotic consumption in Swedish hospitals and to
      review antibiotic stewardship in Swedish hospitals. RESULTS: The main findings
      were: 1) Antibiotic consumption has significantly increased in Swedish hospitals
      over the last decade. The consumption of cephalosporins has decreased, whereas
      that of most other drugs including piperacillin-tazobactam, carbapenems, and
      penicillinase-sensitive and -resistant penicillins has increased and replaced
      cephalosporins. 2) Invasive infections caused by ESBL-producing Escherichia coli
      and Klebsiella pneumoniae have increased, but the proportion of pathogens
      resistant to third-generation cephalosporins causing invasive infections is still
      very low in a European and international perspective. Furthermore, the following
      gaps in knowledge were identified: 1) lack of national, regional, and local data
      on the incidence of antibiotic resistance among bacteria causing hospital
      acquired infections e.g. bloodstream infections and hospital-acquired pneumonia
      data on which standard treatment guidelines should be based; 2) lack of data on
      the incidence of Clostridium difficile infections and the effect of change of
      antibiotic policies on the incidence of C. difficile infections and infections
      caused by antibiotic-resistant pathogens; and 3) lack of prospective surveillance
      programs regarding appropriate antibiotic treatment, including selection of
      optimal antimicrobial drug regimens, dosage, duration of therapy, and adverse
      ecological effects such as increases in C. difficile infections and emergence of
      antibiotic-resistant pathogens. CONCLUSIONS: Evidence-based actions to improve
      antibiotic use and to slow down the problem of antibiotic resistance need to be
      strengthened. The effect of such actions should be analyzed, and standard
      treatment guidelines should be continuously updated at national, regional, and
      local levels.

PMID- 24724824
TI  - Liposome, gel and lipogelosome formulations containing sodium hyaluronate.
AB  - The moisture-imparting effect of sodium hyaluronate (Na-HA) was investigated in
      liposome, gel and lipogelosome topical formulations. Sixteen liposome
      formulations were prepared with or without Na-HA (45 kDa) using various ratios of
      dimyristoylphosphatidylcholine, 1,2-dimyristoyl-sn-glycero-3
      phosphatidylglycerol, dipalmitoylphosphatidylcholine and phospholipon 100H. The
      liposomes were characterized in terms of their structure, composition, zeta
      potential, Na-HA-entrapment capacity and stability. In particular, scanning
      electron microscopy, polarized light microscopy, dynamic light scattering and
      atomic force microscopy were utilized to probe appearance, size and size
      distribution and lamellarity. The work was then extended to gels using the
      gelling agents poloxamer (PXM 188 or 407) and Carbopol or Ultrez 21 (U-21),
      yielding liposome-loaded gel formulations (i.e. lipogelosomes). The in vitro
      release kinetics of Na-HA from liposomes, lipogelosomes and commercial Na-HA
      reference formulations were studied via a flow-through cell method. Among the
      liposomal formulations tested, L6, comprising of Na-HA-loaded phospholipon
      100H:stearylamine:cholesterol (7:1:2), displayed optimal traits. The mean
      particle size, zeta potential and entrapment capacity of L6 were determined as
      1900 nm, -20.9 mV and 15.0%. The optimum lipogelosome, LG4, was obtained by
      incorporating liposome L6 into a U-21 gel at a ratio of 1:1 (w/w). In clinical
      trials, in-house formulations were applied twice daily to 15 female volunteers.
      The two-week benefits were assessed against a commercial product; and in all
      cases, changes of skin humidity, sebum content, pH and wrinkle depth were
      promising. In particular, the LG4 lipogelosome-based formulation had
      significantly improved skin hydration and compliance, as evidenced by a moisture
      content gain of 30.4%.

PMID- 24724828
TI  - Chemoenzymatic dynamic kinetic resolution of primary amines using a recyclable
      palladium nanoparticle catalyst together with lipases.
AB  - A catalyst consisting of palladium nanoparticles supported on amino
      functionalized siliceous mesocellular foam (Pd-AmP-MCF) was used in
      chemoenzymatic dynamic kinetic resolution (DKR) to convert primary amines to
      amides in high yields and excellent ee's. The efficiency of the nanocatalyst at
      temperatures below 70  degrees C enables reaction conditions that are more
      suitable for enzymes. In the present study, this is exemplified by subjecting 1
      phenylethylamine (1a) and analogous benzylic amines to DKR reactions using two
      commercially available lipases, Novozyme-435 (Candida antartica Lipase B) and
      Amano Lipase PS-C1 (lipase from Burkholderia cepacia) as biocatalysts. The latter
      enzyme has not previously been used in the DKR of amines because of its low
      stability at temperatures over 60  degrees C. The viability of the heterogeneous
      Pd-AmP-MCF was further demonstrated in a recycling study, which shows that the
      catalyst can be reused up to five times. 

PMID- 24724829
TI  - Effects of Asn-33 glycosylation on the thermostability of Thermomyces lanuginosus
      lipase.
AB  - AIMS: The study was to examine whether glycosylation could improve the
      thermostability of recombinant Thermomyces lanuginosus lipase (Tll) expressed in
      Pichia pastoris. METHODS AND RESULTS: The Tll gene was synthesized and
      transformed into Pichia pastoris GS115.The recombinant Tll protein was expressed
      and purified, and its glycosylation site was identified by LCMS/MS as Asn-33. Two
      nonglycosylated mutants were constructed and the variant proteins were also
      expressed and purified. Effects of temperature on activities of the wild-type Tll
      and variants were analysed. The glycosylated Tll exhibited better thermostability
      than nonglycosylated variants. CONCLUSIONS: Our experiments have demonstrated the
      improvement of Tll thermostability by Asn-33 glycosylation. SIGNIFICANCE AND
      IMPACT OF THE STUDY: This work has deepened our understanding in the mechanism of
      Tll thermostability and will guide us to directional improvement of lipases and
      even other industrial enzymes.

PMID- 24724830
TI  - Febrile neutropenia: median door-to-needle time - results of an initial audit.
AB  - BACKGROUND: Recently, due to inadequacies during immediate management of patients
      with febrile neutropenia, a new gold standard 'door-to-needle' time of 1 hour for
      the administration of intravenous antibiotics was introduced. OBJECTIVE: The aim
      of this audit was to identify whether that target was being met in our emergency
      department (ED). This is phase 1 of the study which will be followed by
      identification of barriers to the achievement of the target and recommendations
      for improvement. MATERIALS AND METHODS: Data were collected from January 2013 to
      April 2013 of consecutive patients (adult and pediatric age group) who presented
      to the ED with febrile neutropenia for various underlying causes. Fever was
      defined as single oral temperature of >38.3 degrees C (101 degrees F) or a
      temperature of >38.0 degrees C (100.4 degrees F) sustained for more than 1 hour.
      Neutropenia was defined as absolute neutrophil count <0.5 * 10(9)/l, or expected
      to fall below that number. Variables analyzed included age, gender, antibiotics
      administered, underlying diagnosis, day of presentation, and door-to-needle time.
      RESULTS: During the study period, there were n = 81 patients who presented with
      febrile neutropenia. There were n = 49 were males and n = 32 were females. There
      were n = 37 patients in the pediatric age group while rest were adults. Patients
      most commonly had an underlying hematological malignancy (n = 49). A combination
      of piperacillin/tazobactam (4.5 g * Q8hrly) and amikacin (750 mg * once daily)
      was most frequently administered (n = 57) to these patients. The median door-to
      needle time was 45 minutes (range +/- SD: 10 minutes to 6 hours +/- 1 hour 10
      minutes). Long delays of over 4 hours occurred in n = 4 patients (all were
      adults). There were minimal delays observed in pediatric patients due to 'red
      alert' policy implementation. Long delays occurred on weekdays and weekends,
      equally. CONCLUSION: The overall median door-to-needle time was 45 minutes, which
      was in the accepted range. However, delays that occurred demand improvements like
      introducing 'red alert' policy for adult patients, counseling of staff and
      residents, identifying potential barriers in achieving the target time along with
      solutions, and developing hospital-based guidelines on managing patients with
      neutropenic sepsis.

PMID- 24724831
TI  - Catheter ablation of atrial fibrillation in patients with mechanical mitral
      valve: long-term outcome of single procedure of pulmonary vein antrum isolation
      with or without nonpulmonary vein trigger ablation.
AB  - INTRODUCTION: It is unclear whether extended pulmonary vein antrum isolation
      (PVAI) plus nonpulmonary vein (non-PV) trigger elimination prevents more
      arrhythmia recurrence than PVAI alone in patients with mechanical mitral valve
      (MMV) undergoing AF ablation. This study compared the efficacy and long-term
      outcome of 2 ablation strategies--PVAI alone versus extended PVAI plus non-PV
      trigger elimination--for the treatment of AF in patients with MMV. METHODS AND
      RESULTS: One hundred and nine consecutive AF patients with MMV were divided into
      2 groups: standard PVAI was performed in group 1 (N = 45); in group 2 (N = 64)
      PVAI was extended to the LA posterior wall, LA septum, and CS; and all non-PV
      triggers were eliminated. Patients were followed up for 3 years. At the 12th
      month, 7 (15.6%) patients in group 1, and 39 (60.9%) patients in group 2 were
      arrhythmia free (log-rank P < 0.001). Four patients (8.9%; 3 cases of AT and 1
      case of AF) from group 1, and 12 patients (18.8%; 9 cases of AT, and 3 cases of
      AFL) from group 2 experienced very late recurrence. At 36 +/- 7 months follow-up,
      the cumulative recurrence after a single procedure was 42/45 (93.3%) in group 1,
      and 37/64 (57.8%) in group 2 (log-rank P < 0.001). CONCLUSION: Compared with the
      standard PVAI alone, a strategy including extended PVAI and non-PV trigger
      elimination is associated with a higher 12-month and long-term arrhythmia-free
      survival in patients with MMV undergoing AF ablation. Very late recurrence may
      occur years after the initial procedure with focal AT as the most common type of
      recurrent arrhythmia.

PMID- 24724833
TI  - Limoniastrum guyonianum methanol extract induces immunomodulatory and anti
      inflammatory effects by activating cellular anti-oxidant activity.
AB  - Evaluation of the immunomodulatory activity of plant extracts is an interesting
      and growing area of research. In this study, effects of a methanolic extract of
      Limoniastrum guyonianum stems (M extract) on mice immune cell function in vitro
      were investigated. These studies showed that mitogen-induced lymphocyte
      proliferation was dose-dependently inhibited by the extract. Further, the lectin
      induced response appeared to be more sensitive to the suppressive effects of the
      extract than were LPS-stimulated responses. In studies to assess any potential
      effects of extract on innate immunity, the results showed that the extract
      significantly enhanced the killing activity of isolated NK cells. In addition,
      studies here demonstrated that the extract could enhance lysosomal enzyme
      activity and inhibit nitrite oxide (NO) production by murine peritoneal
      macrophages ex vivo, suggesting a potential anti-inflammatory effect in situ. The
      anti-inflammatory activity was concomitant with the cellular anti-oxidant effect
      in macrophages and splenocytes.

PMID- 24724832
TI  - Rhodopsin TM6 can interact with two separate and distinct sites on arrestin:
      evidence for structural plasticity and multiple docking modes in arrestin
      rhodopsin binding.
AB  - Various studies have implicated the concave surface of arrestin in the binding of
      the cytosolic surface of rhodopsin. However, specific sites of contact between
      the two proteins have not previously been defined in detail. Here, we report that
      arrestin shares part of the same binding site on rhodopsin as does the transducin
      Galpha subunit C-terminal tail, suggesting binding of both proteins to rhodopsin
      may share some similar underlying mechanisms. We also identify two areas of
      contact between the proteins near this region. Both sites lie in the arrestin N
      domain, one in the so-called "finger" loop (residues 67-79) and the other in the
      160 loop (residues 155-165). We mapped these sites using a novel tryptophan
      induced quenching method, in which we introduced Trp residues into arrestin and
      measured their ability to quench the fluorescence of bimane probes attached to
      cysteine residues on TM6 of rhodopsin (T242C and T243C). The involvement of
      finger loop binding to rhodopsin was expected, but the evidence of the arrestin
      160 loop contacting rhodopsin was not. Remarkably, our data indicate one site on
      rhodopsin can interact with multiple structurally separate sites on arrestin that
      are almost 30 A apart. Although this observation at first seems paradoxical, in
      fact, it provides strong support for recent hypotheses that structural plasticity
      and conformational changes are involved in the arrestin-rhodopsin binding
      interface and that the two proteins may be able to interact through multiple
      docking modes, with arrestin binding to both monomeric and dimeric rhodopsin. 

PMID- 24724834
TI  - Field measurements of the atmospheric dry deposition fluxes and velocities of
      polycyclic aromatic hydrocarbons to the global oceans.
AB  - The atmospheric dry deposition fluxes of 16 polycyclic aromatic hydrocarbons
      (PAHs) have been measured, for the first time, in the tropical and subtropical
      Atlantic, Pacific, and Indian Oceans. Depositional fluxes for fine (0.7-2.7 MUm)
      and coarse (>2.7 MUm) aerosol fractions were simultaneously determined with the
      suspended aerosol phase concentrations, allowing the determination of PAH
      deposition velocities (vD). PAH dry deposition fluxes (FDD) bound to coarse
      aerosols were higher than those of fine aerosols for 83% of the measurements.
      Average FDD for total (fine + coarse) Sigma16PAHs (sum of 16 individual PAHs)
      ranged from 8.33 ng m(-2)d(-1) to 52.38 ng m(-2)d(-1). Mean FDD for coarse
      aerosol's individual PAHs ranged between 0.13 ng m(-2)d(-1) (Perylene) and 1.96
      ng m(-2)d(-1) (Methyl Pyrene), and for the fine aerosol fraction these ranged
      between 0.06 ng m(-2)d(-1) (Dimethyl Pyrene) and 1.25 ng m(-2)d(-1) (Methyl
      Chrysene). The estimated deposition velocities went from the highest mean vD for
      Methyl Chrysene (0.17-13.30 cm s(-1)), followed by Dibenzo(ah)Anthracene (0.29
      1.38 cm s(-1)), and other high MW PAHs to minimum values of vD for Dimethyl
      Pyrene (<0.04 cm s(-1)) and Pyrene (<0.06 cm s(-1)). Dry depositional processes
      depend on the concentration of PAHs in the suspended aerosol, but also on
      physicochemical properties and environmental variables (vapor pressure, wind
      speed, and on the affinity of aerosols for depositing to the sea surface).
      Empirical parametrizations are proposed to predict the dry depositional
      velocities of semivolatile organic compounds to the global oceans. 

PMID- 24724835
TI  - Using topical benzocaine before lingual frenotomy did not reduce crying and
      should be discouraged.
AB  - AIM: The US Food and Drug Administration has said that oral preparations
      containing benzocaine should only be used in infants under strict medical
      supervision, due to the rare, but potentially fatal, risk of methemoglobinemia.
      This study aimed to determine the analgesic effect of topical application of
      benzocaine prior to lingual frenotomy in infants with symptomatic tongue-tie. We
      hypothesised that the duration of crying immediately following frenotomy with
      topical benzocaine would be shorter than with no benzocaine. METHODS: This
      randomised controlled study compared the length of crying after lingual frenotomy
      in term infants who did, or did not, receive topical application of benzocaine to
      the lingual frenulum prior to the procedure. RESULTS: We recruited 21 infants to
      this study. Crying time was less than one minute in all of the subjects. The
      average length of crying in the benzocaine group (21.6 +/- 13.6 sec) was longer
      than the length of crying in the control group (13.1 +/- 4.0 sec), p = 0.103.
      CONCLUSION: Contrary to our hypothesis, infants who were treated with topical
      benzocaine did not benefit from topical analgesia in terms of crying time. The
      use of benzocaine for analgesia prior to lingual frenotomy in term infants should
      therefore be discouraged.

PMID- 24724836
TI  - Post-traumatic Endophthalmitis Secondary to Keratomycosis Caused by Scedosporium
      apiospermum.

PMID- 24724837
TI  - Reduced NK cell percentage at birth is associated with late onset infection in
      very preterm neonates.
AB  - Immune status in the early life of preterm infants and its association with late
      onset infection has not been fully described. To investigate immune status of
      lymphocyte subsets in the first week in preterm neonates and its association with
      late onset infection, 143 preterm neonates (84 neonates <=32 weeks, 59 neonates
      of 33-36 weeks) and 49 term neonates were recruited. Absolute counts and
      percentages of lymphocyte subsets were measured by flow cytometry in umbilical
      cord or venous blood at birth (in all neonates), on day 3 and 7 (in preterm
      neonates). The presence of late onset infection was recorded in very preterm
      neonates <=32 weeks. At birth, absolute counts of most lymphocyte subsets in all
      preterm neonates and percentages of B cell and NK cell in those <=32 weeks were
      reduced compared with term neonates. Absolute counts of all the subsets in
      preterm neonates showed decline after birth then beginning to rise after day 3.
      Late onset infections were documented in 33 of 84 very preterm infants <=32 weeks
      and 27 of 45 very preterm infants <=30 weeks. Percentages of NK cell at birth in
      very preterm neonates <=30 weeks with late onset infection were significantly
      reduced compared with those without infection (P < 0.01). In conclusion, immune
      status of lymphocyte subsets in preterm neonates at birth is less developmental
      than in term neonates, in spite of the ability of getting improvement in the
      first week. Reduced NK cell percentage at birth would increase the risk of
      subsequent infection in very preterm infants.

PMID- 24724838
TI  - Short communication: prospective comparison of qualitative versus quantitative
      polymerase chain reaction for monitoring virologic treatment failure in HIV
      infected patients.
AB  - Less costly but still accurate methods for monitoring HIV treatment response are
      needed. We prospectively evaluated if a qualitative polymerase chain reaction
      (PCR) amplification assay for virologic monitoring could maintain accuracy while
      reducing costs in Seoul, South Korea. We conducted the first prospective study
      comparing a qualitative PCR amplification of HIV-1 reverse transcriptase (RT)
      versus a commercial real time PCR assay (i.e., viral load) for virologic
      monitoring of 150 patients receiving antiretroviral therapy (ART) between
      November 2011 and August 2012 at an urban hospital in Seoul, South Korea. A total
      of 215 blood plasma samples from 150 patients receiving ART for more than 6
      months were evaluated. Using the individual viral load assay, 12 of 215 (5.6%)
      plasma samples had more than 500 HIV RNA copies/ml. The qualitative PCR
      amplification assay detected individual samples with >=500 HIV RNA copies/ml with
      100% sensitivity. The specificities of the qualitative PCR amplification of the
      HIV-1 RT assay were 94.1%, 93.6%, and 93.2% compared to the real time PCR at 500,
      1,000, and 5,000 threshold of HIV RNA copies/ml, respectively, and $24,940 USD
      would have been saved for 150 patients during 10 months. The qualitative PCR
      amplification of the HIV-1 RT assay might be a useful approach to effectively
      monitor patients receiving ART and save resources.

PMID- 24724839
TI  - Atrial fibrillation in patients with haemophilia: a cross-sectional evaluation in
      Europe.
AB  - Atrial fibrillation (AF) is a common health problem in the general population,
      but data on prevalence or management in patients with haemophilia (PWH) are
      lacking. The aims of this study were to analyse the prevalence of AF and risk
      factors for stroke using a cross-sectional pan-European design and to document
      current anticoagulation practice. The ADVANCE Working Group consists of members
      from 14 European haemophilia centres. Each centre retrieved data on their PWH
      with AF. From the total of 3952 adult PWH, 33 had AF with a mean age of 69 years
      (IQR 62-76). Haemophilia was severe in seven (21%), moderate in six (18%) and
      mild in 20 (61%) patients. The overall AF prevalence was 0.84% and increased with
      age; 0.42% in patients 40-60 years and 3.4% in patients >60 years. The mean CHA2
      DS2 -Vasc score was 1.3 (range 0-4), predominantly determined by age and
      hypertension. Hypertension was reported in 48% of PWH with AF. In 11 patients
      (33%), anticoagulation was started of whom nine aspirin and two vitamin K
      antagonists. Of these 11 patients, nine had mild haemophilia. Anticoagulation was
      given in 42% of patients with a CHA2 DS2 -Vasc score >=2. During follow-up (mean
      57 months), there were no thrombotic events reported, nor increases in bleeding
      severity. The prevalence of AF in haemophilia increases with age and is
      predominantly present in mild haemophilia. PWH have a low stroke risk based on
      their CHA2 DS2 -Vasc scores, that might be even lower considering the
      hypocoagulable state. Only 33% of PWH with AF receives any form of
      anticoagulation therapy. 

PMID- 24724840
TI  - Random telegraph signal in a metallic double-dot system.
AB  - In this work, we investigate the dynamics of a single electron surface trap,
      embedded in a self-assembly metallic double-dot system. The charging and
      discharging of the trap by a single electron is manifested as a random telegraph
      signal of the current through the double-dot device. We find that we can control
      the duration time that an electron resides in the trap through the current that
      flows in the device, between fractions of a second to more than an hour. We
      suggest that the observed switching is the electrical manifestation of the
      optical blinking phenomenon, commonly observed in semiconductor quantum dots. 

PMID- 24724841
TI  - The twisted path to pluripotency.

PMID- 24724842
TI  - Coating extracellular matrix proteins on a (3-aminopropyl)triethoxysilane-treated
      glass substrate for improved cell culture.
AB  - We demonstrate that a (3-aminopropyl)triethoxysilane-treated glass surface is
      superior to an untreated glass surface for coating with extracellular matrix
      (ECM) proteins when used as a cell culture substrate to observe cell physiology
      and behavior. We found that MDCK cells cultured on untreated glass coated with
      ECM removed the coated ECM protein and secreted different ECM proteins. In
      contrast, the cells did not remove the coated ECM protein when seeded on (3
      aminopropyl)triethoxysilane-treated (i.e., silanized) glass coated with ECM.
      Furthermore, the morphology and motility of cells grown on silanized glass
      differed from those grown on non-treated glass, even when both types of glass
      were initially coated with laminin. We also found that cells on silanized glass
      coated with laminin had higher motility than those on silanized glass coated with
      fibronectin. Based on our results, we suggest that silanized glass is a more
      suitable cell culture substrate than conventional non-treated glass when coated
      by ECM for observations of ECM effects on cell physiology. 

PMID- 24724843
TI  - GENESUS: a two-step sequence design program for DNA nanostructure self-assembly.
AB  - DNA has been recognized as an ideal material for bottom-up construction of
      nanometer scale structures by self-assembly. The generation of sequences
      optimized for unique self-assembly (GENESUS) program reported here is a
      straightforward method for generating sets of strand sequences optimized for self
      assembly of arbitrarily designed DNA nanostructures by a generate-candidates-and
      choose-the-best strategy. A scalable procedure to prepare single-stranded DNA
      having arbitrary sequences is also presented. Strands for the assembly of various
      structures were designed and successfully constructed, validating both the
      program and the procedure. 

PMID- 24724844
TI  - Lyophilized Escherichia coli-based cell-free systems for robust, high-density,
      long-term storage.
AB  - Cell-free protein synthesis (CFPS) is a versatile tool for rapid recombinant
      protein production and engineering. One drawback of cell-free technology is the
      necessity to store the major components-cell extracts and energy systems-below
      freezing in bulky aqueous solutions. Here we describe simple methods for
      lyophilizing extracts and preparing powdered energy systems for CFPS. These
      techniques allow for high-density storage of cell-free systems that are more
      robust against temperature and bacterial degradation. Our methods have the
      potential to decrease storage expenses, allow for longer shelf-life of cell
      extracts at room temperature, and enable durable portable protein production
      technologies. 

PMID- 24724845
TI  - Advantages of using the QIAshredder instead of restriction digestion to prepare
      DNA for droplet digital PCR.
AB  - The viscosity of genomic DNA can interfere with digital PCR systems that
      partition samples into oil droplets or microfluidic wells. Restriction digestion
      may reduce the viscosity, but the process is labor-intensive, and the buffer can
      alter the conditions for PCR. DNA fragmentation using the QIAshredder (a
      biopolymer spin column) is faster, may result in more predictable and uniformly
      sized fragments, and avoids the need for restriction buffers that can inhibit
      downstream PCR. In 10 separate head-to-head experiments comparing aliquots of DNA
      processed using the QIAshredder to those digested with RsaI or BsaJI prior to
      droplet digital PCR, we found that the copy numbers measured from the QIAshredded
      DNA tended to be greater than those measured from the digested DNA (average of
      1.35-fold compared with BsaJI; P < 0.0001), even for inputs as high as 1.8 MUg or
      dilution down to the single copy level. 

PMID- 24724846
TI  - Inactivation of an integrated antibiotic resistance gene in mammalian cells to re
      enable antibiotic selection.
AB  - Removing an antibiotic resistance gene allows the same antibiotic to be re-used
      in the next round of genetic manipulation. Here we applied the CRISPR/Cas system
      to disrupt the puromycin resistance gene in an engineered mouse embryonic stem
      cell line and then re-used puromycin selection in the resulting cells to
      establish stable reporter cell lines. With the CRISPR/Cas system, pre-engineered
      sequences, such as loxP or FRT, are not required. Thus, this technique can be
      used to disrupt antibiotic resistance genes that cannot be removed by the Cre
      loxP and Flp-FRT systems. 

PMID- 24724847
TI  - Cellulase inhibition by high concentrations of monosaccharides.
AB  - Biological degradation of biomass on an industrial scale culminates in high
      concentrations of end products. It is known that the accumulation of glucose and
      cellobiose, end products of hydrolysis, inhibit cellulases and decrease glucose
      yields. Aside from these end products, however, other monosaccharides such as
      mannose and galactose (stereoisomers of glucose) decrease glucose yields as well.
      NMR relaxometry measurements showed direct correlations between the initial T2 of
      the liquid phase in which hydrolysis takes place and the total glucose production
      during cellulose hydrolysis, indicating that low free water availability
      contributes to cellulase inhibition. Of the hydrolytic enzymes involved, those
      acting on the cellulose substrate, that is, exo- and endoglucanases, were the
      most inhibited. The beta-glucosidases were shown to be less sensitive to high
      monosaccharide concentrations except glucose. Protein adsorption studies showed
      that this inhibition effect was most likely due to catalytic, and not binding,
      inhibition of the cellulases. 

PMID- 24724848
TI  - Analysis of influenza virus receptor specificity using glycan-functionalized gold
      nanoparticles.
AB  - Recent cases of human infection with avian influenza H5N1 and H7N9 viruses
      underscore an urgent need for techniques that can rapidly assess their potential
      threat to the humans. Determination of the receptor-binding property of influenza
      virus is crucial to direct viral control and prevention measures. Current methods
      to perform this analysis are dependent on immunoanalytical strategies that use
      unstable biological components and complex procedures. We have developed a facile
      colorimetric assay to determine the interaction of the viral hemagglutinin (HA)
      protein with host glycan receptors using glycan-functionalized gold nanoparticles
      (gGNPs). This method is based on the color and absorbance changes of gold probes
      when the solution is simply mixed with HAs or intact viruses. The resulting
      sensitivity and selectivity has enabled HA/virus binding to various glycan
      structures to be differentiated visually and rapidly. Using this system, we have
      screened, in parallel, the receptor specificity of eight representative human and
      avian viral HAs and three whole viruses including an emerging H7N9 strain. Our
      results reveal the detailed receptor-binding profiles of H7N9 virus and its HA
      and show that they effectively bind to human-type receptors. This gGNP-based
      assay represents a strategy that would be helpful for developing simple and
      sensitive systems to probe glycan-mediated biological processes. 

PMID- 24724849
TI  - Challenges in sciatic nerve repair: anatomical considerations.
AB  - OBJECT.: The object of this study was to highlight the challenge of insufficient
      donor graft material in peripheral nerve surgery, with a specific focus on
      sciatic nerve transection requiring autologous sural nerve graft. METHODS: The
      authors performed an anatomical analysis of cadaveric sciatic and sural nerve
      tissue. To complement this they also present 3 illustrative clinical cases of
      sciatic nerve injuries with segmental defects. In the anatomical study, the cross
      sectional area (CSA), circumference, diameter, percentage of neural tissue, fat
      content of the sural nerves, as well as the number of fascicles, were measured
      from cadaveric samples. The percentage of neural tissue was defined as the CSA of
      fascicles lined by perineurium relative to the CSA of the sural nerve surrounded
      by epineurium. RESULTS: Sural nerve samples were obtained from 8 cadaveric
      specimens. Mean values and standard deviations from sural nerve measurements were
      as follows: CSA 2.84 +/- 0.91 mm(2), circumference 6.67 +/- 1.60 mm, diameter
      2.36 +/- 0.43 mm, fat content 0.83 +/- 0.91 mm(2), and number of fascicles 9.88
      +/- 3.68. The percentage of neural tissue seen on sural nerve cross-section was
      33.17% +/- 4.96%. One sciatic nerve was also evaluated. It had a CSA of 37.50
      mm(2), with 56% of the CSA representing nerve material. The estimated length of
      sciatic nerve that could be repaired with a bilateral sural nerve harvest (85 cm)
      varied from as little as 2.5 cm to as much as 8 cm. CONCLUSIONS: Multiple methods
      have been used in the past to repair sciatic nerve injury but most commonly, when
      a considerable gap is present, autologous nerve grafting is required, with sural
      nerve being the foremost source. As evidenced by the anatomical data reported in
      this study, a considerable degree of variability exists in the diameter of sural
      nerve harvests. Conversely, the percentage of neural tissue is relatively
      consistent across specimens. The authors recommend that the peripheral nerve
      surgeon take these points into consideration during nerve grafting as
      insufficient graft material may preclude successful recovery.

PMID- 24724850
TI  - Long-term follow-up of unruptured intracranial aneurysms repaired in California.
AB  - OBJECT: Using a database that enabled longitudinal follow-up, the authors
      assessed the long-term outcomes of unruptured cerebral aneurysms repaired by
      clipping or coiling. METHODS: An observational analysis of the California Office
      of Statewide Health Planning and Development (OSHPD) database, which follows
      patients longitudinally in time and through multiple hospitalizations, was
      performed for all patients initially treated for an unruptured cerebral aneurysm
      in the period from 1998 to 2005 and with follow-up data through 2009. RESULTS:
      Nine hundred forty-four cases (36.5%) were treated with endovascular coiling,
      1565 cases (60.5%) were surgically clipped, and 76 cases were treated with both
      coiling and clipping. There was no significant difference in any demographic
      variable between the two treatment groups except for age (median: 55 years for
      the clipped group, 58 years for the coiled group, p < 0.001). Perioperative (30
      day) mortality was 1.1% in patients with coiled aneurysms compared with 2.3% in
      those with clipped aneurysms (p = 0.048). The median follow-up was 7 years (range
      4-12 years). At the last follow-up, 153 patients (16.2%) in the coiled group had
      died compared with 244 (15.6%) in the clipped group (p = 0.693). The adjusted
      hazard ratio for death at the long-term follow-up was 1.14 (95% CI 0.9-1.4, p =
      0.282) for patients with endovascularly treated aneurysms. The incidence of
      intracranial hemorrhage was similar in the two treatment groups (5.9% clipped vs
      4.8% coiled, p = 0.276). One hundred ninety-three patients (20.4%) with coiled
      aneurysms underwent additional hospitalizations for aneurysm repair procedures
      compared with only 136 patients (8.7%) with clipped aneurysms (p < 0.001).
      Cumulative hospital costs per patient for admissions involving aneurysm repair
      procedures were greater in the clipped group (median cost $98,260 vs $81,620, p <
      0.001) through the follow-up. CONCLUSIONS: For unruptured cerebral aneurysms, an
      observed perioperative survival advantage for endovascular coiling relative to
      that for surgical clipping was lost on long-term follow-up, according to data
      from an administrative database of patients who were not randomly allocated to
      treatment type. A cost advantage of endovascular treatment was maintained even
      though endovascularly treated patients were more likely to undergo subsequent
      hospitalizations for additional aneurysm repair procedures. Rates of aneurysm
      rupture following treatment were similar in the two groups.

PMID- 24724851
TI  - The behavior of residual tumors and facial nerve outcomes after incomplete
      excision of vestibular schwannomas.
AB  - OBJECT: The authors evaluated the behavior of residual tumors and facial nerve
      outcomes after incomplete excision of vestibular schwannomas (VSs). METHODS: The
      case records of all patients who underwent surgical treatment of VSs were
      analyzed. All patients in whom an incomplete excision had been performed were
      analyzed. Incomplete excision was defined as near-total resection (NTR), subtotal
      resection (STR), and partial resection (PR). Tumors in the NTR and STR categories
      were followed up with a wait-and-rescan approach, whereas the tumors in the PR
      category were subjected to a second-stage surgery and were excluded from this
      series. All patients included in the study underwent baseline MRI at the 3rd and
      12th postoperative months, and repeat imaging was subsequently performed every
      year for 7-10 years postoperatively or as indicated clinically. Preoperative and
      postoperative facial function was noted. RESULTS: Of the 2368 patients who
      underwent surgery for VS, 111 patients who had incomplete excisions of VSs were
      included in the study. Of these patients, 73 (65.77%) had undergone NTR and 38
      (34.23%) had undergone STR. Of the VSs, 62 (55.86%) were cystic and 44 (70.97%)
      of these cystic VSs underwent NTR. The residual tumor was left behind on the
      facial nerve alone in 62 patients (55.86%), on the facial nerve and vessels in 2
      patients (1.80%), on the facial nerve and brainstem in 15 patients (13.51%), and
      on the brainstem alone in 25 patients (22.52%). In the 105 patients with normal
      preoperative facial nerve function, postoperative facial nerve function was House
      Brackmann (HB) Grades I and II in 51 patients (48.57%), HB Grade III in 34
      patients (32.38%), and HB Grades IV-VI in 20 patients (19.05%). Seven patients
      (6.3%) showed evidence of tumor regrowth on follow-up MRI. All 7 patients (100%)
      who showed evidence of tumor regrowth had undergone STR. No patient in the NTR
      group exhibited regrowth. The Kaplan-Meier plot demonstrated a 5-year tumor
      regrowth-free survival of 92%, with a mean disease-free interval of 140 months
      (95% CI 127-151 months). The follow-up period ranged from 12 to 156 months (mean
      45.4 months). CONCLUSIONS: The authors' report and review of the literature show
      that there is undoubtedly merit for NTR and STR for preservation of the facial
      nerve. On the basis of this they propose an algorithm for the management of
      incomplete VS excisions. Patients who undergo incomplete excisions must be
      subjected to follow-up MRI for a period of at least 7-10 years. When compared
      with STR, NTR via an enlarged translabyrinthine approach has shown to have a
      lower rate of regrowth of residual tumor, while having almost the same result in
      terms of facial nerve function.

PMID- 24724852
TI  - Letter to the editor: Deep brain stimulation for dystonia.

PMID- 24724853
TI  - Conservative management of cavernous sinus cavernous hemangioma in pregnancy.
AB  - Cavernous sinus cavernous hemangiomas in pregnancy are extremely rare lesions.
      The precise management of these lesions remains unknown. The authors present a
      case of a cavernous hemangioma in pregnancy, centered within the cavernous sinus
      that underwent postpartum involution without surgical intervention. A 34-year-old
      pregnant patient (gravida 1, para 0) presented to an otolaryngologist with
      persistent headache and left-sided facial pain and numbness in the V1
      distribution. While being treated for sinusitis, her symptoms progressed to
      include a left-sided oculomotor palsy and abducens palsy. Magnetic resonance
      imaging without contrast revealed an expansile mass within the left cavernous
      sinus consistent with a cavernous hemangioma. The patient was evaluated by a
      neurosurgeon who recommended close follow-up and postpartum imaging without
      surgical intervention. Although the lesion enlarged during pregnancy, the patient
      was able to undergo an uncomplicated cesarean section at 37 weeks. All facial and
      ocular symptoms resolved by 9 months postpartum, and MRI showed a decrease in
      lesion size and reduced mass effect. The authors conclude that nonsurgical
      management may be a viable approach in patients who have an onset or exacerbation
      of symptoms associated with cavernous sinus cavernous hemangiomas during
      pregnancy because postpartum involution may negate the need for surgical
      intervention.

PMID- 24724854
TI  - Letter to the Editor: Indirect bypass in nonmoyamoya intracranial arterial
      stenosis.

PMID- 24724855
TI  - An isolated primary Rathke's cleft cyst in the cerebellopontine angle.
AB  - Rathke's cleft cysts (RCCs) are benign cysts typically located in the sellar or
      suprasellar region; ectopic isolated lesions are extremely rare. The authors
      describe the case of a 25-year-old man with a giant symptomatic RCC arising
      primarily at the cerebellopontine angle (CPA), only the second case reported thus
      far. The patient presented with a 2-year history of right hearing impairment and
      tinnitus accompanied by vertigo and headache and a 2-week history of right facial
      numbness. Subsequently, he underwent total cyst removal via retrosigmoid
      craniotomy with a good recovery. He experienced no recurrence during a 64-month
      follow-up period. The possible pathogenesis, differential diagnosis, and surgical
      treatment of such cysts are discussed in this article. Isolated ectopic RCCs can
      arise from the ectopic migration of Rathke's pouch cells during the embryonic
      period. It is still difficult to distinguish ectopic RCCs from other cystic
      lesions of the CPA given the lack of specific imaging features. Aggressive
      resection of the cyst wall is not recommended, except when lesions do not closely
      adhere to adjacent structures. 

PMID- 24724856
TI  - Amelioration of oxidative stress and protection against early brain injury by
      astaxanthin after experimental subarachnoid hemorrhage.
AB  - OBJECT.: Aneurysmal subarachnoid hemorrhage (SAH) causes devastating rates of
      mortality and morbidity. Accumulating studies indicate that early brain injury
      (EBI) greatly contributes to poor outcomes after SAH and that oxidative stress
      plays an important role in the development of EBI following SAH. Astaxanthin
      (ATX), one of the most common carotenoids, has a powerful antioxidative property.
      However, the potential role of ATX in protecting against EBI after SAH remains
      obscure. The goal of this study was to assess whether ATX can attenuate SAH
      induced brain edema, blood-brain barrier permeability, neural cell death, and
      neurological deficits, and to elucidate whether the mechanisms of ATX against EBI
      are related to its powerful antioxidant property. METHODS: Two experimental SAH
      models were established, including a prechiasmatic cistern SAH model in rats and
      a one-hemorrhage SAH model in rabbits. Both intracerebroventricular injection and
      oral administration of ATX were evaluated in this experiment. Posttreatment
      assessments included neurological scores, body weight loss, brain edema, Evans
      blue extravasation, Western blot analysis, histopathological study, and
      biochemical estimation. RESULTS: It was observed that an ATX
      intracerebroventricular injection 30 minutes post-SAH could significantly
      attenuate EBI (including brain edema, blood-brain barrier disruption, neural cell
      apoptosis, and neurological dysfunction) after SAH in rats. Meanwhile, delayed
      treatment with ATX 3 hours post-SAH by oral administration was also
      neuroprotective in both rats and rabbits. In addition, the authors found that ATX
      treatment could prevent oxidative damage and upregulate the endogenous
      antioxidant levels in the rat cerebral cortex following SAH. CONCLUSIONS: These
      results suggest that ATX administration could alleviate EBI after SAH,
      potentially through its powerful antioxidant property. The authors conclude that
      ATX might be a promising therapeutic agent for EBI following SAH.

PMID- 24724857
TI  - Comparative inpatient resource utilization for patients undergoing endoscopic or
      microscopic transsphenoidal surgery for pituitary lesions.
AB  - OBJECT.: An increasingly important measure in the health care field is
      utilization of hospital resources, particularly in the context of emerging
      surgical techniques. Despite the recent widespread adoption of the endoscopic
      transsphenoidal approach for pituitary lesion surgery, the health care resources
      utilized with this approach have not been compared with those utilized with the
      traditional microscopic approach. The purpose of this study was to determine the
      drivers of resource utilization by comparing hospital charges for patients with
      pituitary tumors who had undergone either endoscopic or microscopic
      transsphenoidal surgery. METHODS: A complete accounting of all hospital charges
      for 166 patients prospectively enrolled in a surgical quality-of-life study at a
      single pituitary center during October 2011-June 2013 was undertaken. Patients
      were assigned to surgical technique group according to surgeon preference and
      then managed according to a standard postoperative institutional set of orders.
      Individual line-item charges were assigned to categories (such as pharmacy,
      imaging, surgical, laboratory, room, pathology, and recovery unit), and
      univariate and multivariate statistical analyses were conducted. RESULTS: Of the
      166 patients, 99 underwent microscopic surgery and 67 underwent endoscopic
      surgery. Baseline demographic descriptors and tumor characteristics did not
      differ significantly. Mean total hospital charges were $74,703 +/- $15,142 and
      $72,311 +/- $16,576 for microscopic and endoscopic surgery patients, respectively
      (p = 0.33). Furthermore, other than for pathology, charge categories did not
      differ significantly between groups. A 2-step multivariate regression model
      revealed that length of stay was the most influential variable, followed by a
      diagnosis of Cushing's disease, and then by endoscopic surgical technique. The
      model accounts for 42% of the variance in hospital charges. CONCLUSIONS: Study
      findings suggest that adoption of the endoscopic transsphenoidal technique for
      pituitary lesions does not adversely affect utilization of resources for
      inpatients. The primary drivers of hospital charges, in order of importance, were
      length of stay, a diagnosis of Cushing's disease, and, to a lesser extent, use of
      the endoscopic technique. This study also highlights the influence of individual
      surgeon practice patterns on resource utilization.

PMID- 24724858
TI  - Neuro-ophthalmic effects of stenting across the ophthalmic artery origin in the
      treatment of intracranial aneurysms.
AB  - OBJECT.: The benefits of treating intracranial aneurysms in the region of the
      anterior visual pathways are well understood. However, the adverse effects of
      endovascular stenting across the ophthalmic artery have received little
      attention. The authors reviewed their experience with patients who had stents
      deployed across the ophthalmic artery origin. METHODS: Patients' medical charts
      and imaging studies were reviewed to identify all patients with a non-flow
      diverting stent deployed over the ophthalmic artery origin for the treatment of
      intracranial aneurysms. All patients with neuro-ophthalmic complaints were
      referred for formal ophthalmological evaluation. RESULTS: A total of 104
      consecutive patients with 106 aneurysms were identified to meet criteria for
      inclusion in the study cohort. Preoperatively, 30 patients (29%) described
      headache symptoms and 32 patients (31%) reported visual complaints. Of the
      patients with preoperative headaches, 15 (54%) of 28 patients for whom follow-up
      was available experienced improvement in their symptoms. Of the patients with
      preoperative visual complaints, improvement was noted in 11 (41%) of the 27
      patients for whom follow-up was available, 9 (33%) of 27 patients reported no
      change in visual symptoms, and 7 (26%) of 27 patients reported progression of
      symptoms. Visual field defects developing posttreatment were noted to occur in 8
      (7.7%) of 104 patients: 3 with immediate postoperative retinal infarcts, 1 with
      perioperative hemianopia that resolved by the time of discharge, 1 with a
      subjective visual field defect, 1 with subjective migratory visual field defects,
      and 2 with nonspecific visual symptoms. Compressive symptoms from aneurysm mass
      effect were noted in 6 patients preoperatively, with 4 of those patients
      experiencing persistent worsening, resolution in 1 case, and no change in 1 case.
      One patient developed a novel cranial nerve palsy from mass effect in the
      immediate postoperative period. CONCLUSIONS: Deployment of stents across the
      ophthalmic artery origin for the treatment of intracranial aneurysms appears to
      be relatively safe with regard to visual outcomes. Neuro-ophthalmic complaint
      resolution rates were comparable to endovascular procedures that do not employ
      stents, with headache resolution rates comparable to coil-only aneurysm
      obliteration and low rates of retinal ischemic events. For patients presenting
      with mass effect, stent-assisted coiling appears to be less effective than
      microsurgery with decompression for relief of compressive symptoms.

PMID- 24724859
TI  - Supramolecular liquid-crystal gels formed by polyfluorene-based pi-conjugated
      polymer for switchable anisotropic scattering device.
AB  - To overcome the problem of high driving voltage and low contrast ratio in the
      switchable scattering device of conventional liquid-crystal (LC) physical gel, a
      new type of supramolecular LC physical gel has been developed and fabricated
      through the fibrous self-assembly of the polyfluorene-based pi-conjugated
      polymer, poly(9,9-dioctylfluorene-alt-benzothiadiazole) (F8BT), in nematic LC
      mixture E7. It was found that the rubbed interface between the LC molecules and
      polyimide layer can induce the LC physical gels to demonstrate fantastic light
      scattering characteristic. The gels with oriented self-assembled supramolecular
      structures exhibiting significant anisotropic light scattering in the main-chain
      direction of the F8BT molecules under an extremely low driving voltage (ca. 2.7
      V) are reported for the first time. In addition, the contrast ratio can be
      reached exceeding 1000. In contrast to conventional LC physical gels, the large
      reduction of driving voltages of the supramolecular gel provides great
      possibility for application in various electro-optical devices such as tunable
      polarizers, transflective displays, and polarized light modulators. 

PMID- 24724860
TI  - Year-round effects of climate on demographic parameters of an arctic-nesting
      goose species.
AB  - Understanding how climate change will affect animal population dynamics remains a
      major challenge, especially in long-distant migrants exposed to different
      climatic regimes throughout their annual cycle. We evaluated the effect of
      temperature throughout the annual cycle on demographic parameters (age-specific
      survival and recruitment, breeding propensity and fecundity) of the greater snow
      goose (Chen caerulescens atlantica L.), an arctic-nesting species. As this is a
      hunted species, we used the theory of exploited populations to estimate hunting
      mortality separately from natural mortality in order to evaluate climatic effects
      only on the latter form of mortality. Our analysis was based on a 22-year marking
      study (n = 27,150 females) and included live recaptures at the breeding colony
      and dead recoveries from hunters. We tested the effect of climatic covariates by
      applying a procedure that accounts for unexplained environmental variation in the
      demographic parameter to a multistate capture-mark-recapture recruitment model.
      Breeding propensity, clutch size and hatching probability all increased with high
      temperatures on the breeding grounds. First-year survival to natural causes of
      mortality increased when temperature was high at the end of the summer, whereas
      adult survival was not affected by temperature. On the contrary, accession to
      reproduction decreased with warmer climatic conditions during the non-breeding
      season. Survival was strongly negatively related to hunting mortality in adults,
      as expected, but not in first-year birds, which suggests the possibility of
      compensation between natural and hunting mortality in the latter group. We show
      that events occurring both at and away from the breeding ground can affect the
      demography of migratory birds, either directly or through carryover effects, and
      sometimes in opposite ways. This highlights the need to account for the whole
      life cycle of an animal when attempting to project the response of populations to
      future climatic changes.

PMID- 24724861
TI  - Theoretical models of the influence of genomic architecture on the dynamics of
      speciation.
AB  - A long-standing problem in evolutionary biology has been determining whether and
      how gradual, incremental changes at the gene level can account for rapid
      speciation and bursts of adaptive radiation. Using genome-scale computer
      simulations, we extend previous theory showing how gradual adaptive change can
      generate nonlinear population transitions, resulting in the rapid formation of
      new, reproductively isolated species. We show that these transitions occur via a
      mechanism rooted in a basic property of biological heredity: the organization of
      genes in genomes. Genomic organization of genes facilitates two processes: (i)
      the build-up of statistical associations among large numbers of genes and (ii)
      the action of divergent selection on persistent combinations of alleles. When a
      population has accumulated a critical amount of standing, divergently selected
      variation, the combination of these two processes allows many mutations of small
      effect to act synergistically and precipitously split one population into two
      discontinuous, reproductively isolated groups. Periods of allopatry, chromosomal
      linkage among loci, and large-effect alleles can facilitate this process under
      some conditions, but are not required for it. Our results complement and extend
      existing theory on alternative stable states during population divergence,
      distinct phases of speciation and the rapid emergence of multilocus barriers to
      gene flow. The results are thus a step towards aligning population genomic theory
      with modern empirical studies. 

PMID- 24724862
TI  - Abstracts of presentations at the 2014 southern division meeting.

PMID- 24724864
TI  - Methodology to understand how perforin assembles on membranes.

PMID- 24724863
TI  - Impact of prophylactic platelet transfusions on bleeding events in patients with
      hematologic malignancies: a subgroup analysis of a randomized trial.
AB  - BACKGROUND: A recent randomized trial compared a policy of no prophylaxis with a
      policy of prophylactic platelet (PLT) transfusions at counts of fewer than 10 *
      10(9) /L in patients with hematologic malignancies. The results suggested the
      effectiveness of prophylactic PLT transfusions may vary according to patient
      diagnosis and treatment plan. STUDY DESIGN AND METHODS: This article presents
      full subgroup analyses and compares treatment effects between autologous
      hematopoietic stem cell transplantation (autoHSCT; n = 421) and
      chemotherapy/allogeneic HSCT (chemo/alloHSCT; n = 179) patients. RESULTS:
      Prespecified subgroup analysis found that the reduction in proportion of patients
      experiencing WHO Grade 2 to 4 bleeds (main trial outcome) seen in the prophylaxis
      arm was of greater magnitude in chemo/alloHSCT than autoHSCT patients
      (interaction p = 0.04). Analysis of secondary outcomes showed a shorter time to
      first bleeding episode with no prophylaxis in the chemo/alloHSCT group (hazard
      ratio, 1.84; 95% confidence interval CI, 1.21-2.79; p = 0.004) compared to the
      autoHSCT group (hazard ratio, 1.12; 95% CI, 0.85-1.48; p = 0.4; interaction p =
      0.08). The increased number of days with Grade 2 to 4 bleeds with a no
      prophylaxis policy was similar in chemo/alloHSCT (rate ratio, 1.89; 95% CI, 1.10
      3.26) and in autoHSCT patients (rate ratio, 1.43; 95% CI, 1.04-1.97). Both
      subgroups showed significant reductions in PLT transfusions with a no-prophylaxis
      strategy. CONCLUSION: There is evidence that the effectiveness of prophylactic
      PLT transfusions may differ between subgroups, with chemo/alloHSCT patients
      receiving prophylactic PLT transfusions appearing to show a greater reduction in
      bleeding outcomes compared to patients following a no-prophylaxis policy.

PMID- 24724869
TI  - A Cytomegalovirus Retinitis Screening Program: Evaluation of Enrollment Criteria
      for HIV Patients in Singapore.
AB  - PURPOSE: Identification of optimal enrollment criteria for a CMVR screening
      program suitable for a resource-limited environment. METHODS: A prospective audit
      was performed on newly diagnosed HIV patients referred for CMVR screening with
      any of the following four criteria: (1) visual symptoms, (2) low CD4(+) counts
      (<50 cells/uL), (3) AIDS-defining illnesses (ADI), and/or (4) opportunistic
      infections (OI). Odds ratios for each of the demographic factors and enrollment
      criteria were calculated. Sensitivities, specificities, and workload reduction
      for the various combinations were determined. RESULTS: A total of 348 screening
      visits for 176 HIV patients were performed. While individually only ADI was
      statistically significant for increased CMVR risk, the combination of CD4(+)
      counts <50 cells/MUL with either ADI or visual symptoms or all 3 criteria were
      also statistically significant. Two enrollment criteria, ADI and ADI with CD4(+)
      <50 cells/MUL, demonstrated good sensitivities, specificities, and workload
      reduction. CONCLUSION: We propose ADI and possibly CD4(+) counts <50 cells/MUL as
      enrollment criteria for CMVR screening.

PMID- 24724870
TI  - Gestational lead exposure induces developmental abnormalities and up-regulates
      apoptosis of fetal cerebellar cells in rats.
AB  - Lead (Pb), a known environmental toxicant, adversely affects almost all organ
      systems. In this study, we investigated the effects of maternal lead exposure on
      fetal rat cerebellum. Female Sprague-Dawley rats were given lead nitrate in
      drinking water (0, 0.5, and 1%) for two weeks before conception, and during
      pregnancy. Fetuses were collected by caesarian section on gestational day 21 and
      observed for developmental abnormalities. The fetal cerebellar sections from
      control and 1% lead group were stained with cresyl violet. Immunohistochemical
      expressions of p53, Bax, Bcl-2, and caspase 3 were quantified by AnalySIS image
      analyzer (Life Science, Germany). Lead exposure induced developmental
      abnormalities of eyes, ear, limbs, neck and ventral abdominal wall; however,
      these abnormalities were commonly seen in the 1% lead-treated group. In addition,
      lead also caused fetal mortality and reduced body growth in both dose groups and
      reduced brain weight in the 1% lead-treated group. The fetal cerebella from the
      1% lead-treated group showed unorganized cerebellar cortical layers, and
      degenerative changes in granule and Purkinje cells such as the formation of
      clumps of Nissl granules. An increase in Bax and caspase 3, and a decrease in Bcl
      2 (p < 0.05), but not in p53, showed apoptosis of the neurons. In conclusion,
      gestational lead exposure in rats induces fetal toxicity and developmental
      abnormalities. The lead exposure also impairs development of cerebellar layers,
      induces structural changes, and apoptosis in the fetal cerebellar cortex. These
      results suggest that lead exposure during gestation is extremely toxic to
      developing cerebellum in rats.

PMID- 24724871
TI  - Intrauterine growth restriction - a population-based study of the association
      with academic performance and psychiatric health.
AB  - AIM: To investigate whether intrauterine growth restriction (IUGR), resulting in
      small for gestational age (SGA) infants, is associated with increased
      susceptibility to psychiatric problems and academic impairment in late teens.
      METHODS: A cohort of all 10th-grade students in Oslo, Norway, followed up between
      2001 and 2004 (n = 2131), was linked with foetal growth data. IUGR was considered
      equal to SGA at the lowest 2.5th, 5th, and 10th percentiles and appropriate for
      gestational age (AGA) as the highest 90th percentile. Mental health was evaluated
      using the Hopkins Symptoms Check List and the Strength and Difficulties
      Questionnaire, and academic achievements and ambitions were self-reported by the
      students. RESULTS: Psychiatric problems were equally prevalent in all groups.
      However, the SGA girls performed inferiorly compared to their AGA peers in the
      school subjects English [3.6 vs 3.9 (p = 0.03)], mathematics [4.0 vs 4.3 (p =
      0.01)] and social science [4.2 vs 4.4 (p = 0.05)], but not for Norwegian. This
      association was not observed in boys. There was an association between academic
      impairment and prematurity, occurring more frequently among immigrants (p <
      0.001). CONCLUSION: SGA had a small negative impact on academic achievements in
      adolescent girls, but not boys. There was no association between SGA and
      psychiatric problems in either gender.

PMID- 24724872
TI  - Development of (trimethylsilyl)ethyl ester protected enolates and applications in
      palladium-catalyzed enantioselective allylic alkylation: intermolecular cross
      coupling of functionalized electrophiles.
AB  - The development of (trimethylsilyl)ethyl ester protected enolates is reported.
      The application of this class of compounds in palladium-catalyzed asymmetric
      allylic alkylation is explored, yielding a variety of alpha-quaternary six- and
      seven-membered ketones and lactams. Independent coupling partner synthesis
      engenders enhanced allyl substrate scope relative to traditional beta-ketoester
      substrates; highly functionalized alpha-quaternary ketones generated by the union
      of (trimethylsilyl)ethyl beta-ketoesters and sensitive allylic alkylation
      coupling partners serve to demonstrate the utility of this method for complex
      fragment coupling. 

PMID- 24724873
TI  - The role of notch signaling in bone marrow niche.
AB  - OBJECTIVE: Bone marrow (BM) niche is a three-dimensional structure composed of a
      series of cells and it is one of the most controversial topics in hematological
      malignancies, leukemia, and even metastasis. Here, we review the relationship
      between Notch signaling and different fates of stem cells and other BM niche
      cells. METHODS: Relevant English-language literature were searched and retrieved
      from PubMed (2000-2013) using the terms Notch signaling, BM niche, and microRNAs
      (miRNAs). DISCUSSION: Notch signaling pathway is a signaling system involved in
      cellular processes such as proliferation, differentiation, and apoptosis. The
      notch signaling pathway components are associated with interaction between
      leukemic, metastatic, and normal cells and their microenvironment. miRNAs play an
      important role in expression and regulation of signaling molecules. It is
      necessary to evaluate the relationship between aberrant miRNA expression and
      notch signaling such as miR-128 and miR-30 in glioma and angiogenesis with notch
      signaling, respectively. CONCLUSIONS: Characterizing malignant cells and future
      studies focus on better understanding the variety of cancers and apoptosis with
      activated Notch signaling pathway, may remain promising this signaling system as
      a safe and effective therapeutic target.

PMID- 24724874
TI  - Current treatment of ascending colon volvulus in horses: a survey of ACVS
      Diplomates.
AB  - OBJECTIVE: To report the results of a survey of opinions on current treatments
      and estimated outcomes of ascending colon volvulus in horses. STUDY DESIGN: Web
      based survey. SAMPLE POPULATION: American College of Veterinary Surgeons (ACVS)
      Diplomates (n = 151) who perform gastrointestinal surgery in horses. METHODS:
      ACVS Diplomates with credentials in the large animal specialty obtained by
      examination in 2010 or earlier (n = 410) were solicited by e-mail to complete a
      web-based survey designed to determine ascending colon volvulus treatment
      preferences and outcomes. RESULTS: Responses were obtained from 162 ACVS
      Diplomates, of which 151 currently performed gastrointestinal surgery in horses.
      Horses surgically treated with ascending colon volvulus accounted for <= 20
      cases/year and primary treatment was most often anatomic reduction with or
      without pelvic flexure enterotomy. Median estimated survival rate was 70% and
      surgical treatments were not associated with estimated survival (P = .27).
      Diplomates identified early surgical correction as the single most important
      factor impacting survival of horses surgically treated for ascending colon
      volvulus. CONCLUSIONS: Reported survival rates for horses with ascending colon
      volvulus were good. Respondents indicated this might be due in part to early
      surgical treatment. Survey investigations can provide preliminary data for future
      prospective studies and facilitate a consensus among Diplomates in treatment of
      surgical disease.

PMID- 24724875
TI  - Implementing substance abuse group therapy clinical trials in real-world
      settings: challenges and strategies for participant recruitment and therapist
      training in the Women's Recovery Group Study.
AB  - BACKGROUND AND OBJECTIVES: Open-enrollment group therapy research is challenged
      by the participant recruitment necessary to ensure continuous group enrollment.
      We present successful strategies to overcome the following barriers during the
      Women's Recovery Group (WRG) two-site clinical trial (N = 158): maintenance of
      sample size and balanced gender randomization during continuous enrollment,
      maintenance of group attendance, and training and retention of therapists over
      the 24-month continuous group enrollment. METHODS: To increase recruitment, we
      targeted referral sources yielding the highest enrollment conversion at each
      site. Group sessions were consistently held regardless of group size. Therapists
      were trained in two teams allowing for coverage and uninterrupted treatment over
      24 months. RESULTS: At both sites recruitment and enrollment increased with each
      successive quarter. Sample size and end date targets were met without disruptions
      in treatment. Group therapists reported high satisfaction with their training and
      treatment experiences. DISCUSSION AND CONCLUSIONS: These strategies supported
      targeted enrollment and study duration, stability of open-enrollment group
      therapy frame, and therapist retention and satisfaction. SCIENTIFIC SIGNIFICANCE:
      Applying these strategies can aid in providing evidence-based group therapy in
      both clinical and research settings.

PMID- 24724876
TI  - Nationwide dissemination of contingency management: the Veterans Administration
      initiative.
AB  - BACKGROUND: Contingency management (CM) is an empirically validated intervention
      but one not often applied in practice settings in the US. OBJECTIVES: The aim of
      this article is to describe the Veterans Administration (VA) nationwide
      implementation of CM treatment. METHODS: In 2011, the VA called for integration
      of CM in its intensive outpatient substance abuse treatment clinics. As part of
      this initiative, the VA funded training and ongoing implementation support, and
      it provided direct funds for reinforcers and other intervention costs. RESULTS:
      Over 100 clinics received this funding in 2011, and CM has been implemented in
      over 70 substance abuse treatment clinics since August 2011. CONCLUSIONS: This
      training and implementation experience has been highly successful and represents
      the largest scale training in evidence-based treatments for substance use
      disorders in the VA health care system to date. SCIENTIFIC SIGNIFICANCE: This
      program may serve as a model for training in evidence-based treatments.

PMID- 24724877
TI  - Sex differences in smoking cue reactivity: craving, negative affect, and
      preference for immediate smoking.
AB  - BACKGROUND AND OBJECTIVES: Female smokers have greater difficulty quitting,
      possibly due to increased reactivity to smoking-related cues. This study assessed
      sex differences in craving, affect, and preference for immediate smoking after
      cue exposure. METHODS: Regular smokers (n = 60; 50% female) were exposed to
      smoking and neutral cues in separate, counterbalanced sessions. Outcomes included
      changes in craving and affect and preference for immediate smoking following cue
      exposure. RESULTS: Findings indicated that women exhibited greater preference for
      immediate smoking (p = .004), and reported greater cue-induced increases in
      cigarette craving (p = .046) and negative affect (p = .025). DISCUSSION AND
      CONCLUSIONS: These data suggest that women may have greater difficulty inhibiting
      smoking after cue exposure, possibly as a consequence of greater increases in
      craving and negative affect. SCIENTIFIC SIGNIFICANCE AND FUTURE DIRECTIONS:
      Findings suggest a mechanism that may contribute to greater cessation failure
      among female smokers.

PMID- 24724878
TI  - Indirect effects of 12-session seeking safety on substance use outcomes: overall
      and attendance class-specific effects.
AB  - OBJECTIVES: This study examined in- and post-treatment mediation effects of a 12
      session dose of Seeking Safety (SS)-an integrative cognitive behavioral treatment
      for comorbid PTSD and SUDs-on alcohol and cocaine outcomes in comparison to
      Women's Health Education (WHE) in a seven-site randomized controlled
      effectiveness trial. METHODS: Women (n = 353) enrolled in outpatient substance
      abuse treatment, who had experienced multiple traumas in childhood and/or
      adulthood and who had comorbid PTSD, were randomly assigned to receive SS or WHE
      delivered in open enrollment groups for 12 sessions in 6 weeks (unlike the full
      25-topic SS protocol). Data were analyzed under two forms of longitudinal
      mediation analysis, each accounting for changes over time in group membership and
      group context, respectively. RESULTS: Women in SS, compared to WHE, showed
      significantly steeper decreases in PTSD frequency and severity, which in turn,
      showed significant impact in reducing both cocaine and alcohol use. This pattern
      was strongest for those who completed most of the treatment sessions, which was
      the majority of patients in the trial; these patterns only emerged during the in
      treatment phase. CONCLUSIONS: Use of an integrated approach to PTSD/SUD such as
      SS can be helpful to more rapidly reduce PTSD, which consequently reduce SUD
      symptoms, particularly for those who attend most of the available treatment
      sessions. SCIENTIFIC SIGNIFICANCE: This is one of the first studies to illustrate
      such effects in treating comorbid PTSD and SUD in the context of a highly
      impaired population delivered by community-based providers. (Am J Addict
      2014;23:218-225).

PMID- 24724879
TI  - Predictors of drinking and functional outcomes for men and women following
      inpatient alcohol treatment.
AB  - BACKGROUND AND OBJECTIVES: This prospective study uses path analytic models to
      examine baseline characteristics associated with both functioning and drinking
      outcomes 12 months after inpatient alcohol treatment. METHODS: Alcohol-dependent
      participants (N = 101) were recruited during inpatient alcohol treatment and
      assessed monthly 1 year after discharge. RESULTS: Alcohol severity was negatively
      associated with education and self-efficacy; marital status was positively
      associated with self-efficacy; and education and self-efficacy were negatively
      associated with drinking outcomes. Low alcohol severity, not having a depression
      diagnosis, and being married were associated with less social support impairment,
      which was in turn associated with better drinking outcomes. Having a history of
      sexual abuse did not influence drinking outcomes. However, having a history of
      sexual abuse was negatively associated with global functioning. CONCLUSIONS AND
      SCIENTIFIC SIGNIFICANCE: Drinking outcomes were associated with education, self
      efficacy, social support, and diagnosis of depression at baseline; however,
      global functioning 1 year following treatment was primarily and negatively
      associated with sexual abuse history. Future treatment research should include
      measures of both functioning and drinking behavior outcomes.

PMID- 24724881
TI  - Does stimulant use impair housing outcomes in low-demand supportive housing for
      chronically homeless adults?
AB  - BACKGROUND: Recent research suggests low-demand housing (i.e., not contingent
      upon abstinence) is effective in helping people exit homelessness, even among
      recent active substance users. Whether active users of illicit drugs and
      stimulants have worse housing outcomes than primary alcohol users, however, is
      unknown. METHODS: A total of 149 participants in a multisite supportive housing
      program who reported high levels of active substance use at program entry were
      classified as either (1) predominantly "Alcohol Use" (>10 of 30 days alcohol, but
      not >10 days of drug use) or (2) "Illicit Drug Use" (>10 of 30 days any single
      illicit drug use with or without alcohol use). Sub-analysis of the "Illicit Drug
      Use" group compared participants reporting high levels of "Stimulant Use" (>10
      days cocaine, crack, or methamphetamine use) to those with high levels of "Non
      stimulant Use" (>10 days marijuana or other non-stimulant drug use). Group
      differences in housing outcomes were examined with mixed model multivariate
      regression. RESULTS: During 24-month follow-up, days housed increased
      dramatically for both the "Alcohol Use" and the "Illicit Drug Use" groups without
      significant differences. Sub-analysis of illicit drug users showed stimulant use
      was associated with fewer days housed (p = .01) and more days homeless (p = .02)
      over time. CONCLUSIONS: Among illicit drug users, stimulant users have somewhat
      less successful housing outcomes than other active drug and alcohol users, though
      both groups maintained substantial housing improvements in low-demand housing.

PMID- 24724880
TI  - Cannabis withdrawal in chronic, frequent cannabis smokers during sustained
      abstinence within a closed residential environment.
AB  - OBJECTIVES: Chronic, frequent cannabis smokers may experience residual and offset
      effects, withdrawal, and craving when abstaining from the drug. We characterized
      the prevalence, duration, and intensity of these effects in chronic frequent
      cannabis smokers during abstinence on a closed research unit. METHODS: Non
      treatment-seeking participants (N = 29 on admission, 66% and 34% remaining after
      2 and 4 weeks) provided subjective effects data. A battery of five instruments
      was computer-administered daily to measure psychological, sensory, and physical
      symptoms associated with cannabinoid intoxication and withdrawal. Plasma and oral
      fluid specimens were concurrently collected and analyzed for cannabinoids.
      Outcome variables were evaluated as change from admission (Day 0) with regression
      models. RESULTS: Most abstinence effects, including irritability and anxiety were
      greatest on Days 0-3 and decreased thereafter. Cannabis craving significantly
      decreased over time, whereas decreased appetite began to normalize on Day 4.
      Strange dreams and difficulty getting to sleep increased over time, suggesting
      intrinsic sleep problems in chronic cannabis smokers. Symptoms likely induced by
      residual drug effects were at maximum intensity on admission and positively
      correlated with plasma and oral fluid cannabinoid concentrations on admission but
      not afterward; these symptoms showed overall prevalence higher than cannabis
      withdrawal symptoms. CONCLUSIONS: The combined influence of residual/offset drug
      effects, withdrawal, and craving was observed in chronic cannabis smokers during
      monitored abstinence. Abstinence symptoms were generally more intense in the
      initial phase, implying importance of early intervention in cannabis quit
      attempts. Sleep disturbance persisting for an extended period suggests that
      hypnotic medications could be beneficial in treating cannabis dependence.

PMID- 24724882
TI  - Prevalence of psychiatric disorders among heroin users who received methadone
      maintenance therapy in Taiwan.
AB  - BACKGROUND: Many patients under methadone maintenance treatment are present with
      comorbid psychiatric symptoms. OBJECTIVE: We wish to examine the prevalence of
      psychiatric disorders among heroin users who received methadone maintenance
      therapy (MMT) in Taiwan. METHODS: By combining the National Health Insurance
      Research database and Center for Disease Control database, 18,271 heroin users
      who received MMT were defined as the subject group and after matching age and
      sex, 73,084 patients were randomly selected as the control group. RESULTS: The 1
      year prevalence of any psychiatric disorder, any psychotic disorder, neurotic and
      other nonpsychotic disorder among MMT patients and control group were 13.14%
      versus 2.50% (OR 5.89, CI 5.53-6.27), 4.21% versus 1.29% (OR 3.38, CI 3.07-3.72),
      and 9.89% versus 1.31% (OR 8.25, CI 7.62-8.94), respectively. CONCLUSION: The
      prevalence of any co-morbid psychiatric disorder among MMT patients is almost six
      times higher than the control group. SCIENTIFIC SIGNIFICANCE: A thorough
      psychiatric screening and appropriate aggressive intervention should be
      incorporated into an effective methadone treatment program.

PMID- 24724883
TI  - High levels of opioid analgesic co-prescription among methadone maintenance
      treatment clients in British Columbia, Canada: results from a population-level
      retrospective cohort study.
AB  - BACKGROUND AND OBJECTIVES: The non-medical use of prescription opioids (PO) has
      increased dramatically in North America. Special consideration for PO
      prescription is required for individuals in methadone maintenance treatment
      (MMT). Our objective is to describe the prevalence and correlates of PO use among
      British Columbia (BC) MMT clients from 1996 to 2007. METHODS: This study was
      based on a linked, population-level medication dispensation database. All
      individuals receiving 30 days of continuous MMT for opioid dependence were
      included in the study. Key measurements included the proportion of clients
      receiving >7 days of a PO other than methadone during MMT from 1996 to 2007.
      Factors independently associated with PO co-prescription during MMT were assessed
      using generalized linear mixed effects regression. RESULTS: 16,248 individuals
      with 27,919 MMT episodes at least 30 days in duration were identified for the
      study period. Among them, 5,552 individuals (34.2%) received a total of 290,543
      PO co-prescriptions during MMT. The majority (74.3%) of all PO dispensations >7
      days originated from non-MMT physicians. The number of PO prescriptions per
      person-year nearly doubled between 1996 and 2006, driven by increases in
      morphine, hydromorphone and oxycodone dispensations. PO co-prescription was
      positively associated with female gender, older age, higher levels of medical co
      morbidity as well as higher MMT dosage, adherence, and retention. CONCLUSION AND
      SCIENTIFIC SIGNIFICANCE: A large proportion of MMT clients in BC received co
      occurring PO prescriptions, often from physicians and pharmacies not delivering
      MMT. Experimental evidence for the treatment of pain in MMT clients is required
      to guide clinical practice.

PMID- 24724885
TI  - Alcohol and drug use in groups of cannabis users: results from a survey on drug
      use in the Swedish general population.
AB  - BACKGROUND AND OBJECTIVES: Although cannabis is well studied in the scientific
      literature, relatively little is known about the relationship between the
      frequency of cannabis use and the use of alcohol and other drugs. The aim of this
      study was to identify differences between frequent and occasional cannabis users
      with respect to the use of other illicit drugs, hazardous alcohol use, and
      unauthorized use of prescription drugs. METHODS: Results from a questionnaire on
      drug use taken by 22,095 individuals in the Swedish general population were
      analyzed with a logistic regression model. Active cannabis use was defined as
      having used cannabis in the past 12 months. Use of cannabis two-to-three times
      per week or more was classified as frequent use. RESULTS: Cannabis users were
      more likely to report hazardous alcohol use, use of other illicit drugs, and
      unauthorized use of prescription drugs than were non-users. Within the group of
      active cannabis users, frequent cannabis use, compared to occasional use, was
      associated with the use of other illicit drugs and negatively associated with
      hazardous alcohol use. DISCUSSION AND CONCLUSIONS: The association between
      cannabis use and hazardous alcohol use, use of other illicit drugs, and
      unauthorized use of prescription drugs was expected. However, the negative
      association between frequent cannabis use and hazardous alcohol use among active
      cannabis users was surprising. This indicates that frequent cannabis users may
      differ from more occasional users in clinical needs. SCIENTIFIC SIGNIFICANCE:
      These results show a previously unknown characteristic of the association between
      frequency of cannabis use and hazardous alcohol use in the general population.

PMID- 24724884
TI  - Relationships of behavioral measures of frontal lobe dysfunction with underlying
      electrophysiology in cocaine-dependent patients.
AB  - BACKGROUND AND OBJECTIVES: Despite evidence that frontal lobe functioning is
      impaired in cocaine-dependent individuals, relationships between behavioral
      measures of frontal dysfunction and electrophysiological measures of inhibition
      in cocaine use have not been explored. METHODS: Using the Frontal Systems
      Behavior Scale (FrSBe), frontal dysfunction was assessed in a group of abstinent
      cocaine-dependent subjects (N = 49) and healthy controls (N = 32). Using
      transcranial magnetic stimulation (TMS) and evoked potential (EP)-based
      electrophysiological measures of inhibition, we assessed associations between
      these measures and FrSBe estimates of frontal dysfunction. RESULTS: Patients had
      significantly higher FrSBe scores for executive dysfunction, disinhibition, and
      apathy than controls. Lower TMS-based resting motor thresholds (ie,
      hyperexcitability) were significantly associated with higher executive
      dysfunction scores in the patients. CONCLUSIONS AND SCIENTIFIC SIGNIFICANCE:
      Relationships between FrSBe scores and TMS-based measures highlight
      neurophysiological aberrations underlying frontal lobe dysfunction in cocaine
      abusers. TMS and EP measures may be useful probes of the intermediary steps
      between frontal lobe dysfunction and addictive behavior.

PMID- 24724886
TI  - Investigating the association between strategic and pathological gambling
      behaviors and substance use in youth: could religious faith play a differential
      role?
AB  - OBJECTIVES: This study investigated the link between gambling behaviors and the
      use of alcohol, drugs, and nonprescribed prescription medications, while
      exploring the moderating role of distinct religious faiths. METHODS: In 2010, 570
      students from the American University of Beirut completed a self-reported,
      anonymous English questionnaire, which included lifetime gambling and past-year
      substance use measures. RESULTS: Half (55%) were lifetime gamblers, of whom, 12%
      were probable pathological gamblers. About 60% were strategic gamblers. Lifetime
      gamblers were more than twice as likely as nongamblers to report past-year
      illegal drug use and alcohol abuse. Probable pathological gamblers were also more
      than four times as likely as nongamblers to report nonmedical prescription drug
      use, illegal drug use, and alcohol abuse. Compared to nonstrategic gamblers,
      strategic gamblers had more than three times the odds of illegal drug and
      cigarette use. The link between alcohol abuse and gambling was stronger among
      Christians than Muslims. Conversely, Muslims were more likely to report the co
      occurrence of various gambling behaviors (lifetime, probable pathological, and
      strategic gambling) with both illegal drug use and cigarette use. CONCLUSIONS:
      Gambling and substance use behaviors were strongly linked in this sample of youth
      from Lebanon, corroborating the evidence from North America. Particularly novel
      are the co-occurrence of pathological gambling and nonmedical prescription drug
      use and the potential differential role of religion. (Am J Addict 2014;23:280
      287).

PMID- 24724887
TI  - Pharmacogenetics of naltrexone and disulfiram in alcohol dependent, dually
      diagnosed veterans.
AB  - BACKGROUND: Disulfiram and naltrexone were evaluated in treatment of individuals
      with co-occurring alcohol dependence and other Axis I disorders (e.g., Major
      Depression). We explored pharmacogenetic interactions in genotyped subjects.
      METHODS: Alcohol dependent (AD) subjects received naltrexone alone, placebo
      alone, disulfiram with placebo or disulfiram with naltrexone. They were genotyped
      for OPRM1 rs1799971 (Asn40Asp), and DBH rs1611115 (C-1021T). N = 107 male
      European-American subjects were included. RESULTS: There were no significant
      interactions with OPRM1. DBH interacted with naltrexone on the primary outcome of
      abstinence from heavy drinking (chi(2) (1) = 5.23, p = .02). "T" allele carriers
      on naltrexone had more abstinence compared to "CC" subjects on naltrexone (FET, p
      = .01). "T" allele carriers on naltrexone had the highest overall rates of
      abstinence from heavy drinking (>90%). Also, DBH genotype interacted with
      disulfram (F(1,17) = 7.52, p = .01) on drinks per drinking day with less drinking
      for subjects with the "CC" genotype than for T allele carriers on disulfiram.
      CONCLUSIONS: DBH*rs1611115*T associated with better response to naltrexone, while
      for those on disulfiram that drank, "CC" subjects drank less than T carriers. For
      rs1799971*G, we did not replicate findings from previous studies showing a more
      favorable response to NTX, possibly due to the small available sample. SCIENTIFIC
      SIGNIFICANCE: Genotyping rs1611115 may be useful in understanding inter
      individual differences in AD treatment response. FUTURE DIRECTIONS: Further study
      of rs1611115 pharmacogenetics is warranted.

PMID- 24724888
TI  - Attachment security and problematic substance use in low-income, suicidal,
      African American women.
AB  - BACKGROUND AND OBJECTIVES: While secure attachment may buffer the effect of
      adverse early experiences on the development of behavioral problems in children,
      whether attachment security may provide resilience against problematic substance
      use in adulthood is less clear, and addressed by this study. METHODS: We examined
      relations between attachment security and problematic substance use in 356
      African American women recruited for a suicide prevention/intervention study.
      Problematic substance use was defined as a positive screen on either the Brief
      Michigan Alcoholism Screening Test or the Drug Abuse Screening Test-10.
      Attachment security was assessed using the Secure Subscale of the Relationship
      Scales Questionnaire. Associations between demographic and psychosocial variables
      (age, education, unemployment, homelessness, attachment security, past childhood
      maltreatment, current exposure to intimate partner violence, and depressive
      symptoms) and problematic substance use were determined using logistic regression
      analyses. RESULTS: Participants averaged 35.1 +/- 10.0 years of age, and
      exhibited significant psychosocial challenges. More secure attachment was
      independently associated with a lower likelihood of problematic drug use (OR =
      .516, 95% CI (.343-.777), p <= .01); and the problematic use of either alcohol or
      drugs (OR = .563, 95% CI (.374-.849), p <= .01). Attachment security, along with
      childhood maltreatment, age, and homelessness, accounted for 25.5% of the
      variance in problematic substance use. DISCUSSION AND CONCLUSIONS: Participants
      who reported greater attachment security were significantly less likely to engage
      in problematic substance use. SCIENTIFIC SIGNIFICANCE: Future research should
      explore attachment security as a resilience factor against problematic substance
      use.

PMID- 24724889
TI  - Alcoholics Anonymous and twelve-step recovery: a model based on social and
      cognitive neuroscience.
AB  - BACKGROUND: In the course of achieving abstinence from alcohol, longstanding
      members of Alcoholics Anonymous (AA) typically experience a change in their
      addiction-related attitudes and behaviors. These changes are reflective of
      physiologically grounded mechanisms which can be investigated within the
      disciplines of social and cognitive neuroscience. OBJECTIVE: This article is
      designed to examine recent findings associated with these disciplines that may
      shed light on the mechanisms underlying this change. METHOD: Literature review
      and hypothesis development. RESULTS: Pertinent aspects of the neural impact of
      drugs of abuse are summarized. After this, research regarding specific brain
      sites, elucidated primarily by imaging techniques, is reviewed relative to the
      following: Mirroring and mentalizing are described in relation to experimentally
      modeled studies on empathy and mutuality, which may parallel the experiences of
      social interaction and influence on AA members. Integration and retrieval of
      memories acquired in a setting like AA are described, and are related to studies
      on storytelling, models of self-schema development, and value formation. A model
      for ascription to a Higher Power is presented. CONCLUSION: The phenomena
      associated with AA reflect greater complexity than the empirical studies on which
      this article is based, and certainly require further elucidation. Despite this
      substantial limitation in currently available findings, there is heuristic value
      in considering the relationship between the brain-based and clinical phenomena
      described here. SCIENTIFIC SIGNIFICANCE: There are opportunities for the study of
      neuroscientific correlates of Twelve-Step-based recovery, and these can
      potentially enhance our understanding of related clinical phenomena.

PMID- 24724890
TI  - Epidemiological trends and the advances of treatments of amphetamine-type
      stimulants (ATS) in China.
AB  - BACKGROUND AND OBJECTIVES: Amphetamine-type stimulants (ATS) have quickly spread
      and been widely abused in many parts of the world, particularly in China. This
      review focuses on and describes the epidemiological trends and the advances of
      treatments of ATS in China. METHODS: A descriptive study based on literature
      identified from searches of the China National Knowledge Infrastructure (1979
      2013), PubMed databases, hand-picked references, and online references with
      emphasis on epidemiology, treatment and traditional Chinese medicine. This review
      covers some traditional Chinese treatments and their complementary Western
      approaches. RESULTS AND CONCLUSIONS: The epidemiological trends of ATS in China
      have led to its being 2.2 times the rate of morphine abuse and second only to
      marijuana abuse. The treatment programs in China have used traditional herbal
      approaches as well as acupuncture, often in combination with Western medications
      such as fluoxetine for depression associated with ATS abuse. Other herbal
      treatments have reversed the cardiac arrhythmias associated with ATS
      intoxication, and acupuncture has been used successfully for the protracted
      depressive and somatic symptoms of ATS withdrawal over a period of 3 months.
      SCIENTIFIC SIGNIFICANCE: These traditional Chinese treatments may be increasingly
      available to the world, but will remain a consistent complementary therapy for
      ATS in China and the Far East, where ATS has become such a prevalent problem.

PMID- 24724891
TI  - Differential diagnosis for a stable patient maintained on buprenorphine who gives
      a urine toxicology screen negative for buprenorphine.

PMID- 24724892
TI  - In vitro antifungal effect and inhibitory activity on biofilm formation of seven
      commercial mouthwashes.
AB  - OBJECTIVE: To investigate the antifungal ability of seven over-the-counter
      mouthwashes against planktonic and sessile Candida albicans and Candida krusei.
      MATERIALS AND METHODS: The seven mouthwashes studied were Listerine, compound
      chlorhexidine solution, povidone iodine solution (PV-I), cetylpyridinium chloride
      solution, Colgate Plax, Crest Prohealth Mouthwash, and NaHCO3 . The antifungal
      ability of each mouthwash against ATCC90028, ATCC6258, and 10 clinical C.
      albicans isolates was tested using disk diffusion tests, the broth microdilution
      method, and biofilm testing with two different XTT-reduction assays. Fluconazole
      was used as a positive control, and the experiments were performed in triplicate.
      RESULTS: Chlorhexidine and cetylpyridinium chloride had the largest inhibition
      zones for ATCC90028 and ATCC6258 (18.6 +/- 3.5 and 19 +/- 1.6 mm, respectively).
      Cetylpyridinium chloride was the most effective at inhibiting all of the
      planktonic C. albicans strains and ATCC6258 with the minimum inhibitory
      concentration (MIC). As the maturity of the biofilms increased, the change in
      sessile cell MIC of the mouthwashes was much smaller than that of fluconazole.
      For the mature biofilms, chlorhexidine, PV-I, and cetylpyridinium chloride
      produced the greatest reductions in metabolism (60-80%). CONCLUSION: Most of
      these seven mouthwashes had significant antifungal activity for both planktonic
      and sessile Candida species.

PMID- 24724893
TI  - Suzuki-Miyaura coupling of halophenols and phenol boronic acids: systematic
      investigation of positional isomer effects and conclusions for the synthesis of
      phytoalexins from pyrinae.
AB  - The Suzuki-Miyaura couplings of o-, m-, and p-halophenols with o-, m-, and p
      phenol boronic acids were investigated for all combinations under standardized
      conditions, using Pd/C as a heterogeneous catalyst and water as a solvent. In the
      case of iodophenols, conventional heating was used, while for bromophenols
      significantly better results could be obtained using microwave irradiation. This
      systematic study revealed that 2,4'-biphenol is particularly difficult to access,
      irrespective of the starting materials used, but that these difficulties can be
      overcome by using different additives. The conclusions drawn from this
      investigation allowed us to identify conditions for the protecting group-free or
      minimized total synthesis of biaryl-type phytoalexins. These compounds possess
      antibacterial activity and are produced by fruit trees as a response to microbial
      infection. 

PMID- 24724894
TI  - Mitotic checkpoint proteins Mad1 and Mad2 - structural and functional
      relationship with implication in genetic diseases.
AB  - In normal cells, the accuracy of chromosome segregation which assures cells
      euploidy depends on mitosis mechanics and on proper functioning of a specific
      complex of proteins represented by the error-checking spindle assembly checkpoint
      (SAC). SAC proteins are deeply involved in correct cell divisions, but some of
      these, such as mitotic arrest-deficient proteins (Mad1 and Mad2), are critical.
      Mad1 and Mad2 are involved in preventing "wrong" cellular divisions which lead to
      cellular aneuploidy and are recognized as inductors of genetic disorders, as well
      as activators of oncoproteins. To clarify aneuploidy involvement in the evolution
      of cancer or other genetic disorders, structural and functional specificity of
      spindle checkpoint proteins have been analyzed, but the process is still poorly
      understood. In order to better understand SAC proteins involvement in initiation
      of cancer and other genetic disorders, here we review studies that conducted to
      relevant structural and functional information regarding these proteins. The
      results of these studies suggest that minor changes in structure and
      functionality of SAC proteins are able to generate aneuploidy. Therefore, a
      deeper understanding of Mad1 and Mad2 structural changes obtained by experimental
      and theoretical studies could open new perspectives of genetic medicine. 

PMID- 24724895
TI  - Lacosamide derivatives with anticonvulsant activity as carbonic anhydrase
      inhibitors. Molecular modeling, docking and QSAR analysis.
AB  - Lacosamide is an anticonvulsant drug which presents carbonic anhydrase
      inhibition. In this paper, we analyzed the apparent relationship between both
      activities performing a molecular modeling, docking and QSAR studies on 18
      lacosamide derivatives with known anticonvulsant activity. Docking results
      suggested the zinc-binding site of carbonic anhydrase is a possible target of
      lacosamide and lacosamide derivatives making favorable Van der Waals interactions
      with Asn67, Gln92, Phe131 and Thr200. The mathematical models revealed a poor
      relationship between the anticonvulsant activity and molecular descriptors
      obtained from DFT and docking calculations. However, a QSAR model was developed
      using Dragon software descriptors. The statistic parameters of the model are:
      correlation coefficient, R=0.957 and standard deviation, S=0.162. Our results
      provide new valuable information regarding the relationship between both
      activities and contribute important insights into the essential molecular
      requirements for the anticonvulsant activity. 

PMID- 24724896
TI  - 3D-QSAR approaches in drug design: perspectives to generate reliable CoMFA
      models.
AB  - Drug discovery is mostly guided by innovative and knowledge by the application of
      experimental and computational approaches. Quantitative structure-activity
      relationships (QSAR) have a critical task in the discovery and optimization of
      lead compounds, thereby contributing to the development of new chemical entities.
      3D-QSAR methods use the information of the tridimensional molecular structure of
      ligands and can be applied to elucidate the relationships between 3D molecular
      interactions and their measured biological property, therefore, providing a
      rational approach for the development of new potential compounds. The purpose of
      this review is to provide a perspective of the utility of 3DQSAR approaches in
      drug design, focusing on progress, challenges and future orientations. The
      essential steps involved to generate reliable and predictive CoMFA models are
      discussed. Moreover, we present an example of application of a CoMFA study to
      derive 3D-QSAR models for a series of oxadiazoles inhibitors of Schistosoma
      mansoni Thioredoxin Glutathione Reductase (SmTGR). 

PMID- 24724897
TI  - Assessing the validity of QSARs for ready biodegradability of chemicals: an
      applicability domain perspective.
AB  - Several classical and two recently proposed Applicability Domain (AD) approaches
      were implemented on a set of three classification models retrieved from a
      published study to assess the ready biodegradability of chemicals. Each model was
      associated with an optimal AD approach based on its ability to a) retain maximum
      test molecules within the model's AD, b) be appropriate for the strategy used
      towards model development and c) show reasonably converging results with those
      derived with other AD approaches used. A decision criterion was also set to
      evaluate the AD of two consensus models that were developed in the original
      study. An overview of test molecules excluded from the AD of all the five
      biodegradability models was provided including an attempt to identify the major
      structural features and molecular descriptors possibly relevant in deciding upon
      their ready biodegradability. Apart from the test set, an overview of the results
      derived on the external validation set molecules was provided. 

PMID- 24724898
TI  - QSAR multi-target in drug discovery: a review.
AB  - The main purpose of the present review is to summarize the most significant works
      up to date in the field of multi-target QSAR (mt-QSAR), in order to emphasize the
      importance that this technique has acquired over the last decade. Unlike
      traditional QSAR techniques, mt-QSAR permits to calculate the probability of
      activity of a given compound against different biological or pharmacological
      targets. In simple terms, a single equation for multiple outputs. To emphasize
      more the importance of the mt-QSAR in the field of drug discovery, we also
      present a novel mt-QSAR model, made on purpose by our research group, for the
      prediction of the susceptibility of Gram + and Gram - anaerobic bacteria. 

PMID- 24724899
TI  - QSAR in flavonoids by similarity cluster prediction.
AB  - Quantitative Structure-Activity Relationships based on molecular descriptors
      calculated with correlation weights within the hypermolecule, considered to mimic
      the investigated correlational space, was performed on a set of 40 flavonoids
      (PubChem database). The best models describing log P and LD50 of this set of
      flavonoids were validated by the leave-one-out procedure, in the external test
      set and in a new version of prediction by using clusters of similar molecules.
      The best prediction was provided by the similarity cluster procedure. 

PMID- 24724900
TI  - QSTR studies regarding the ECOSAR toxicity of benzene-carboxylic acid' esters to
      fathead minnow fish (Pimephales promelas).
AB  - The present work employs 152 benzene-carboxylic acid' esters having computed the
      toxicity within the range [2.251, 10.222] for fathead minnow fish (Pimephales
      promelas). Calibration set includes many pairs having very similar chemical
      structure, size, shape and hydrophilicity, but very different value of ECOSAR
      toxicity or vice versa. The QSTR study, which uses all esters as calibration set,
      emphasized a large percent (16.2%) of outliers. In this QSTR study most of the
      estimated values of toxicity for outliers are much lower than ECOSAR toxicity.
      The LogP and some aromaticity descriptors are predictors. The best QSTR for
      esters having low value (< 5.5) of ECOSAR toxicity and the best QSTR for esters
      having high value (> 5.5) of ECOSAR toxicity are obtained when the number of
      outliers is very small. These QSTRs are different enough and highlight opposite
      influences of certain descriptors on toxicity. The results emphasize two
      possibilities: (a) the esters having low value of ECOSAR toxicity and the esters
      having high value of ECOSAR toxicity are included in two different classes from
      the point of view of structure-toxicity relationship and/or (b) many high values
      of ECOSAR toxicity are wrong. By comparison, a QSTR using experimental values of
      toxicity against rats for 37 benzene-carboxylic esters included in the same
      database gives good correlation experimental/computed values of toxicity, the
      number of outliers is null and the result of validation test is good. 

PMID- 24724901
TI  - A probabilistic analysis about the concepts of difficulty and usefulness of a
      molecular ranking classification.
AB  - Discerning between the concepts of difficulty and usefulness of a molecular
      ranking classification is of significant importance in virtual design chemistry.
      Here, both concepts are viewed from the statistical and practical point of view
      according to the standard definitions of enrichment and statistical significance
      p-values. These parameters are useful not only to compare distinct rankings
      obtained for the same molecular database, but also in order to compare the ones
      established in distinct molecular sets from an objective point of view. 

PMID- 24724902
TI  - Extracorporeal life support for acute respiratory failure. A systematic review
      and metaanalysis.
AB  - RATIONALE: Extracorporeal life support (ECLS) for acute respiratory failure has
      increased as a result of technological advancements and promising results from
      recent studies as compared with historical trials. OBJECTIVES: Systematically
      review the effect of ECLS compared with mechanical ventilation on mortality,
      length of stay, and adverse events in respiratory failure. METHODS: Data sources
      included were MEDLINE, EMBASE, and CENTRAL (through to October 2013). Any
      randomized controlled trial (RCT) or observational study comparing ECLS to
      mechanical ventilation in adults was used. Two authors independently abstracted
      the data. Our primary outcome was mortality. Secondary outcomes included
      intensive care unit length of stay, hospital length of stay, and adverse events.
      A sensitivity analysis was performed restricted to RCTs and quasi-RCTs, and a
      number of predefined subgroups were identified to explore heterogeneity.
      MEASUREMENTS AND MAIN RESULTS: Ten studies (four RCTs, six observational studies,
      1,248 patients) were included. There was no significant difference in hospital
      mortality with ECLS as compared with mechanical ventilation (risk ratio [RR],
      1.02; 95% confidence interval [CI], 0.79-1.33; I(2) = 77%). When restricted to
      venovenous ECLS studies of randomized trials and quasi-randomized trials (three
      studies; 504 patients), there was a decrease in mortality with ECLS compared with
      mechanical ventilation (RR, 0.64; 95% CI, 0.51-0.79; I(2) = 15%). There were
      insufficient study-level data to evaluate most secondary outcomes. Bleeding was
      significantly greater in the ECLS group (RR, 11.44; 95% CI, 3.11-42.06; I(2) =
      0%). In the H1N1 subgroup (three studies; 364 patients), ECLS was associated with
      significantly lower hospital mortality (RR, 0.62; 95% CI, 0.45-0.8; I(2) = 25%).
      CONCLUSIONS: ECLS was not associated with a mortality benefit in patients with
      acute respiratory failure. However, a significant mortality benefit was seen when
      restricted to higher-quality studies of venovenous ECLS. Patients with H1N1-acute
      respiratory distress syndrome represent a subgroup that may benefit from ECLS.
      Future studies are needed to confirm the efficacy of ECLS as well as the optimal
      configuration, indications, and timing for adult patients with respiratory
      failure.

PMID- 24724903
TI  - Bioremediation of chlorinated ethenes in fractured bedrock and associated changes
      in dechlorinating and nondechlorinating microbial populations.
AB  - The use of enhanced in situ anaerobic bioremediation (EISB) and bioaugmentation
      in fractured bedrock is limited compared to its use in granular media. We
      evaluated EISB for the treatment of trichloroethene (TCE)-impacted groundwater in
      fractured carbonate rock at a site in Southern Ontario, Canada, with cool average
      groundwater temperature (~ 13  degrees C). Borehole-connectivity, contaminant
      concentrations, and groundwater properties were investigated. Changes in
      dechlorinating and nondechlorinating populations (fermenters, acetogens,
      methanogens, and sulfate reducers) were assessed via quantitative PCR (qPCR).
      During biostimulation with ethanol, concentrations of TCE daughter products cis
      dichloroethene (cDCE) and vinyl chloride (VC) decreased in association with an
      enrichment of vcrA (VC reductive dehalogenase)-carrying Dehalococcoides, whereas
      ethene production was only moderate. Following bioaugmentation with the mixed
      dechlorinating culture KB-1, greater concentrations of chloride-a product of
      dechlorination-was observed in most wells; in addition, ethene production
      increased significantly in monitoring well locations that had strong hydraulic
      connectivity to the groundwater recirculation system, while Dehalococcoides and
      vcrA concentrations did not appreciably vary. Interestingly, increases of 3-4
      orders of magnitude of an ethanol-fermenting Bacteroidetes population also
      present in KB-1 were correlated to improved conversion to ethene, an observation
      which suggests there could be a causal relationship-for example, better syntrophy
      and/or synergy among bacterial populations. 

PMID- 24724904
TI  - The complete mitochondrial genome of the Simao Chinese indigenous dog.
AB  - In this study, the whole mtDNA genome of Simao Chinese indigenous dog was
      amplified and sequenced. Our data showed that the whole mtDNA genome of Simao
      Chinese indigenous dog includes 16,730 base pairs (bps). The Simao Chinese
      indigenous dog mitochondrial genome included structural organization and base
      composition of the rRNAs, tRNAs and protein-coding genes, as well as
      characteristics of tRNAs. 

PMID- 24724905
TI  - Preparing silk fibroin nanofibers through electrospinning: further heparin
      immobilization toward hemocompatibility improvement.
AB  - Sodium heparin (HS) was immobilized on the surface of the silk fibroin nanofibers
      (FS) prepared by electrospinning with the objective of improving the
      hemocompatibility of the fibers for application as scaffolds in tissue
      engineering. The nanofiber mats of silk fibroin without (MF-FS) and with (MF
      FS/HS) immobilized heparin were characterized through scanning electron
      microscopy (SEM), Fourier-transform infrared spectroscopy with attenuated total
      reflectance (FTIR-ATR), thermogravimetric analyses (TGA), energy dispersive
      spectroscopy (EDS), contact angle, chemical analysis, and biological tests. The
      formation of hydrogen bonds between the silk fibroin and heparin was discussed
      based on FTIR-ATR spectra. The amount of immobilized heparin was quantified
      through papain/N-acetyl-l-cysteine digestion followed by dimethylmethylene blue
      complexation. Furthermore, the samples with immobilized HS showed higher
      hydrophilic capability compared to samples without HS due to lower contact
      angles. It was possible to verify that the capillary end-to-collector distance of
      8.5 cm and flow rate of 0.35 mL h(-1) used in the electrospinning process at 20
      kV are good conditions for obtaining a small average fiber diameter maintaining
      the amount of immobilized heparin on MF-FS/HS in ca. 4% w/w. Biological analysis
      showed that no hemolysis is provoked by MF-FS and MF-FS/HS mat fragments and
      those such mats are not toxic to Vero cells. However, the MF-FS/HS showed higher
      cell growth and proliferation than MF-FS, indicating an improvement in the
      hemocompatibility of the material due to heparin immobilization. 

PMID- 24724906
TI  - The heterogeneous HLA genetic composition of the Brazilian population and its
      relevance to the optimization of hematopoietic stem cell donor recruitment.
AB  - The aim of this study was to investigate the human leukocyte antigen (HLA)
      molecular variation across the Brazilian population in order to determine
      possible regional differences, which would be highly relevant to optimizing donor
      recruitment strategies in hematopoietic stem cell transplantation (HSCT) and
      understanding the population genetic background of this heterogeneous country.
      HLA data of 551 HSCT donors from five Brazilian regions were characterized by
      high-resolution DNA alleles at the HLA-A, -B, -C, -DRB1 and -DQB1 loci and
      compared with other populations in Brazil and worldwide populations. Allele and
      haplotype frequencies were estimated. The analysis was performed to assess Hardy
      Weinberg equilibrium (HWE) and linkage disequilibrium (LD) among different loci
      in each recruitment center. Genetic variation was explored through genetic
      distance analyzed by using a new algorithm based on linear algebra, taking into
      account geographic regions of Brazil. The results indicated a heterogeneous
      genetic composition of the Brazilian population, such that HLA allele and
      haplotype frequencies exhibit different distributions among Brazilian regions,
      which has important implications for donor matching. In addition, a pronounced
      differentiation was observed by the absence of clustering of the regional
      populations in the reduced-dimension space. These data may be useful for
      increasing donor recruitment with more genetic representativeness in the
      Brazilian Volunteer Bone Marrow Donors Registry (REDOME). 

PMID- 24724908
TI  - Risk of interstitial lung disease associated with EGFR-TKIs in advanced non-small
      cell lung cancer: a meta-analysis of 24 phase III clinical trials.
AB  - PURPOSE: To assess the risk of interstitial lung disease (ILD) with epidermal
      growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) gefitinib,
      erlotinib, and afatinib. METHOD: PubMed databases were searched for relevant
      articles. Statistical analyses were conducted to calculate the summary incidence,
      odds ratio (OR), and 95% confidence intervals (CIs) by using either random
      effects or fixed-effect models. RESULTS: The incidence of all-grade and high
      grade (? grade 3) ILD associated with EGFR-TKIs was 1.6% (95% CI, 1.0-2.4%) and
      0.9% (95% CI, 0.6%-1.4%), with a mortality of 13.0% (95% CI, 7.6-21.6%). Patients
      treated with EGFR-TKIs had a significantly increased risk of developing all-grade
      (OR, 1.74; 95% CI, 1.25-2.43; P = 0.001) and high-grade (OR, 4.38; 95% CI, 2.18
      8.79; P<0.001) ILD. No significant difference in the risk of ILD was found in sub
      group analysis according to EGFR-TKIs, percentage of EGFR mutation, study
      location, EGFR-TKIs-based regimens, and controlled therapy. CONCLUSIONS:
      Treatment with EGFR-TKIs is associated with a significantly increased risk of
      developing ILD.

PMID- 24724909
TI  - Assessment of stress tolerance acquisition in the heat-tolerant derivative
      strains of Bifidobacterium animalis subsp. lactis BB-12 and Lactobacillus
      rhamnosus GG.
AB  - AIMS: The purpose of this study was to investigate the heat-shock response at
      molecular level in Lactobacillus rhamnosus GG, Bifidobacterium animalis subsp.
      lactis BB-12 and their heat-tolerant derivatives and to characterize the changes
      that make the derivatives more robust in terms of heat stress. METHODS AND
      RESULTS: The study strains were exposed for 2 h to a heat-shock treatment, Bif.
      animalis subsp. lactis BB-12 and its derivative at 50 degrees C and the Lact.
      rhamnosus GG and its derivative at 60 degrees C. Protein synthesis before and
      after heat shock was examined using proteomics and RT-qPCR. The analysis revealed
      that the regulation of seven proteins in both strain pairs was modified as a
      response to heat or between the original and the derivative strain. The
      comparison of wild-type strains and the heat-tolerant derivatives suggests that
      the acquisition of heat tolerance in the Bif. animalis subsp. lactis BB-12
      derivative is due to a slightly increased constitutive level of chaperones, while
      in Lact. rhamnosus GG derivative, the main reason seems to be a higher ability to
      induce the production of chaperones. CONCLUSIONS: This study revealed possible
      markers of heat tolerance in B. lactis and Lact. rhamnosus strains. SIGNIFICANCE
      AND IMPACT OF STUDY: This study increases our knowledge on how Lactobacillus and
      Bifidobacterium strains may acquire heat tolerance. These findings may be useful
      for improving the heat tolerance of existing probiotic strains as well as
      screening new heat-tolerant strains.

PMID- 24724910
TI  - Serpiginous choroiditis in a referral clinic in India: visual field changes and
      clinical correlates.
AB  - PURPOSE: To report the visual field changes in patients with serpiginous
      choroiditis as seen in a referral clinic in India. METHODS: A retrospective
      noncomparative case series was conducted. Twenty-nine eyes of 17 patients who
      were diagnosed with serpiginous choroiditis were included in the study. Clinical
      findings were recorded. Visual field was measured with a Humphrey visual field
      analyzer. Information obtained was entered into SPSS 17.0 and analyzed. RESULTS:
      There was a male preponderance (8:2). Age at presentation ranged from 14 to 53
      years. Eleven subjects (64.7%) had bilateral involvement at presentation. Mean
      visual acuity improved to 0.35 after treatment. Visual field changes were seen in
      28 eyes and the mean deviation value was maintained after treatment (-8.5, 7.19
      SD). Multiple foci of defects (usually central or paracentral scotoma co-existing
      with isolated field defects in the nasal or temporal field) were the commonest
      form of visual field defect detected. CONCLUSION: Patients with serpiginous
      choroiditis had a stable visual field defects after 6 months of treatment. The
      need for visual field monitoring in these patients is underscored.

PMID- 24724911
TI  - HLA-DRB1*07:01 allele is primarily associated with the Diego a alloimmunization
      in a Brazilian population.
AB  - BACKGROUND: The Diego blood group presents a major polymorphic site at Residue
      854, causing a proline (Di(b) antigen) to leucine (Di(a) antigen) substitution.
      Di(a) alloimmunization has been observed among Asian and Native South American
      populations. Considering that Brazilians represent a genetically diverse
      population, and considering that we have observed a high incidence of Di(a)
      alloimmunization, we typed HLA-DRB1 alleles in these patients and performed in
      silico studies to investigate the possible associated mechanisms. STUDY DESIGN
      AND METHODS: We studied 212 alloimmunized patients, of whom 24 presented
      immunoglobulin G anti-Di(a) , 15 received Di(a+) red blood cells and were not
      immunized, and 1008 were healthy donors. HLA typing was performed using
      commercial kits. In silico analyses were performed using the TEPITOPEpan software
      to identify Diego-derived anchor peptide binding to HLA-DRB1 molecules. Residue
      alignment was performed using the IMGT/HLA for amino acid identity and homology
      analyses. RESULTS: HLA-DRB1*07:01 allele was overrepresented in Di(a) 
      alloimmunized patients compared to nonimmunized patients and to healthy donors.
      Two motifs were predicted to be potential epitopes for Di(a) alloimmunization,
      the WVVKSTLAS motif was predicted to bind several HLA-DR molecules, and the
      FVLILTVPL motif exhibited highest affinity for the HLA-DRB1*07:01 molecule.
      Pocket 4 of the DRB1*07:01 molecule contained specific residues not found in
      other HLA-DRB1 molecules, particularly those at Positions 13(Y), 74(Q), and
      78(V). CONCLUSION: Individuals carrying the HLA-DRB1*07:01 allele present an
      increased risk for Di(a) alloimmunization. The identification of susceptible
      individuals and the knowledge of potential sensitization peptides are relevant
      approaches for transfusion care, diagnostic purposes, and desensitization
      therapies.

PMID- 24724912
TI  - Phenotypic differences in leucocyte populations among healthy preterm and full
      term newborns.
AB  - The immune system of neonates has been considered functionally immature, and due
      to their high susceptibility to infections, the aim of this study was to analyse
      the phenotypic differences in leucocyte populations in healthy preterm and full
      term newborns. We evaluated the absolute numbers and frequencies of dendritic
      cells (DCs) and DC subsets, monocytes and T and B lymphocytes and subsets in the
      cord blood of healthy moderate and very preterm (Group 1), late preterm (Group 2)
      and full-term (Group 3) newborns and in healthy adults, as controls, by flow
      cytometry. The analyses revealed statistically higher absolute cell numbers in
      neonates compared with adults due to the characteristic leucocytosis of neonates.
      We observed a lower frequency of CD80(+) myeloid and plasmacytoid DCs in Group 1
      and reduced expression of TLR-4 on myeloid DCs in all neonates compared with
      adults. TLR-2(+) monocytes were reduced in Group 1 compared with Groups 2 and 3,
      and TLR-4(+) monocytes were reduced in Groups 1 and 2 compared with Group 3. The
      frequencies and numbers of naive CD4(+) T and CD19(+) B cells were higher in the
      three groups of neonates compared with adults, while CD4(+) effector and effector
      memory T cells and CD19(+) memory B cells were elevated in adults compared with
      neonates, as expected. Our study provides reference values for leucocytes in cord
      blood from term and preterm newborns, which may facilitate the identification of
      immunological deficiencies in protection against extracellular pathogens. 

PMID- 24724913
TI  - Evaluating national guidelines for the prophylactic treatment of respiratory
      syncytial virus in children with congenital heart disease.
AB  - AIM: This is the first study to evaluate compliance with the 2003 Swedish
      national guidelines for prophylactic treatment of respiratory syncytial virus
      (RSV) in children with congenital heart disease (CHD). We estimated the relative
      risk (RR) of children with CHD being hospitalised with a RSV infection, studied
      the extent to which RSV prophylactic treatment with palivizumab corresponded to
      the guidelines and determined the morbidity of children with CHD who developed
      RSV infection despite prophylaxis. METHODS: This national observational study
      comprised prospectively registered data on 219 children with CHD treated with
      palivizumab, medical records on RSV cases and information on hospitalisation
      rates of children with CHD and RSV infection. RESULTS: The calculated RR of
      children with CHD being hospitalised with RSV infection was 2.06 (95% CI 1.6-2.6;
      p < 0.0001) compared with children without CHD. Approximately half of the
      patients (49%) born before the RSV season and 25% born during the RSV season did
      not start treatment as recommended by the guidelines. CONCLUSION: Having CHD
      increased the rate and estimated RR of children being hospitalised with RSV
      infection. The guidelines were not followed for about half of the children born
      before a RSV season and a quarter of the children born during a RSV season and
      need updating.

PMID- 24724914
TI  - Expression of P-glycoprotein and CYP3A4 along the porcine oral-gastrointestinal
      tract: implications on oral mucosal drug delivery.
AB  - OBJECTIVES: To characterize the expression of Pgp and CYP3A4 along the oral
      gastrointestinal (GI) tract for understanding the potential roles of CY3A4 and
      Pgp in oral mucosal drug delivery. DESIGN: Porcine buccal mucosa, sublingual
      mucosa, esophagus and jejunum, ileum and colon tissues were used for studying the
      mRNA and protein expression of CYP3A4 and Pgp. mRNA and protein were determined
      using real-time quantitative polymerase chain reaction (PCR) and western blot,
      respectively. The expression levels of CYP3A4 and Pgp in different segments of
      oral-GI tract were compared. RESULTS: Levels of Pgp mRNA were significantly lower
      (14-40 times lower) in buccal and sublingual mucosa than that in intestine. In
      contrast, higher levels of CYP3A4 mRNA were observed in the oral mucosa as
      compared to that in intestine, but the difference was not statistically
      different. The levels of Pgp protein along the oral-GI tract followed the order:
      sublingual ~buccal ~esophagus < jejunum ~ileum ~ colon while the expression of
      CYP3A4 protein in the oral mucosa was similar to that in intestine. CONCLUSION:
      Expression of Pgp in oral mucosa is lower than that in intestine, while the
      expression of CYP3A4 in oral mucosa is similar to that in intestine. Because of
      lower Pgp in oral mucosa, oral mucosal drug delivery can be used as an
      alternative strategy to avoid the coordination of Pgp and CYP3A4 metabolism in
      drug absorption. However, CYP3A4-dependent metabolism may play a role in oral
      mucosal drug delivery as in per oral-GI absorption.

PMID- 24724916
TI  - Use of 2-bromophenylboronic esters as benzyne precursors in the Pd-catalyzed
      synthesis of triphenylenes.
AB  - ortho-Substituted aryl boronates are introduced as aryne precursors for
      transition-metal-catalyzed transformations. On treatment with (t)BuOK and Pd(0),
      metal-bound aryne intermediates are formed that undergo effective trimerization
      to form useful triphenylene compounds. For meta-substituted arynes, the 3:1
      product ratio in favor of non-C3 symmetric material is indicative of a benzyne
      mechanism. 

PMID- 24724915
TI  - Conscious and anaesthetised Gottingen mini-pigs as an in-vivo model for buccal
      absorption - pH-dependent absorption of metoprolol from bioadhesive tablets.
AB  - The potential of buccal mucosa as a site for systemic absorption has attracted
      increased attention in recent years creating a need for new predictive in-vivo
      models. The aim of this study was to evaluate anaesthetised and conscious
      Gottingen mini-pigs as a model for buccal drug absorption by testing pH-dependent
      absorption of metoprolol from a solid dosage form. Buccal tablets buffered to pH
      6.2 and pH 8.9, oral liquid and intravenous injection were tested in four
      conscious and anaesthetised Gottingen mini-pigs in a non-randomised cross-over
      study. Blood samples were collected and processed before analysis by ultra
      performance liquid chromatography with tandem mass spectrometry detection. An ex
      vivo flow retention model was applied to study release and retention of the
      bioadhesive buccal tablets. The Tmax obtained from the two buccal conscious
      groups (55 +/- 5 and 35 +/- 5 min) were significantly different to the buccal
      anaesthetised groups (120 +/- 0 and 165 +/- 15 min) for buccal tablet pH 6.2 and
      pH 8.9, respectively. Also, the absolute bioavailability from the anaesthetised
      buccal tablet pH 8.9 (20.7 +/- 4.0%) had a significant increase compared to all
      other buccal tablet groups. In conclusion, this study showed a pH-dependent
      absolute bioavailability of metoprolol when administrated as bioadhesive buccal
      tablets to anaesthetised mini-pigs. The anaesthesia was found to delay the time
      to reach maximal plasma concentration of metoprolol as compared to the conscious
      pig model when administrated as buccal tablets.

PMID- 24724917
TI  - Cheetahs and wild dogs show contrasting patterns of suppression by lions.
AB  - Top predators can dramatically suppress populations of smaller predators, with
      cascading effects throughout communities, and this pressure is often
      unquestioningly accepted as a constraint on mesopredator populations. In this
      study, we reassess whether African lions suppress populations of cheetahs and
      African wild dogs and examine possible mechanisms for coexistence between these
      species. Using long-term records from Serengeti National Park, we tested 30 years
      of population data for evidence of mesopredator suppression, and we examined six
      years of concurrent radio-telemetry data for evidence of large-scale spatial
      displacement. The Serengeti lion population nearly tripled between 1966 and 1998;
      during this time, wild dogs declined but cheetah numbers remained largely
      unchanged. Prior to their local extinction, wild dogs primarily occupied low lion
      density areas and apparently abandoned the long-term study area as the lion
      population 'saturated' the region. In contrast, cheetahs mostly utilized areas of
      high lion density, and the stability of the cheetah population indicates that
      neither high levels of lion-inflicted mortality nor behavioural avoidance inflict
      sufficient demographic consequences to translate into population-level effects.
      Population data from fenced reserves in southern Africa revealed a similar
      contrast between wild dogs and cheetahs in their ability to coexist with lions.
      These findings demonstrate differential responses of subordinate species within
      the same guild and challenge a widespread perception that lions undermine cheetah
      conservation efforts. Paired with several recent studies that document fine-scale
      lion-avoidance by cheetahs, this study further highlights fine-scale spatial
      avoidance as a possible mechanism for mitigating mesopredator suppression.

PMID- 24724918
TI  - Global DNA methylation: uncommon event in oral lichenoid disease.
AB  - OBJECTIVES: Accumulating evidence indicates that aberrant DNA methylation is
      closely related to oral carcinogenesis, and it has been shown that methylation
      changes might be used as prognostic biomarker in oral squamous cell carcinoma.
      Oral lichenoid disease (OLD) is the most common oral potentially malignant
      disorder in our region. The aim of this study was to perform the first wide DNA
      methylation study in OLD in order to investigate the relevance of DNA methylation
      changes in this premalignant disorder. MATERIALS AND METHODS: Two different
      Illumina microarray platforms, namely the GoldenGate Cancer Panel I and the
      HumanMethylation27 DNA Analysis BeadChip, were utilized in the discovery phase to
      interrogate the methylation profile of 59 OLD cases and 9 healthy individuals.
      Top-ranked genes were further validated by pyrosequencing in a second sample set
      consisting of 160 OLD and 65 controls. RESULTS: Our results show that the
      frequency of aberrant DNA methylation is rare in OLD, and this finding was
      further corroborated by pyrosequencing in the biological validation. CONCLUSIONS:
      These findings reinforce the notion that molecular alterations associated with
      oral carcinogenesis do not seem to be common events in OLD, which in turn might
      explain the low rate of malignization of this disorder.

PMID- 24724919
TI  - Maternal, placental and fetal exposure to bisphenol A in women with and without
      preeclampsia.
AB  - OBJECTIVES: We aimed to investigate potential association between the exposure of
      bisphenol A (BPA) and preeclampsia. METHODS: Concentrations of BPA were assessed
      in 58 pregnancies including 35 normotensive and 23 preeclamptic women, using a
      highly sensitive gas chromatography-mass spectrometry (GC-MS) method. RESULTS:
      BPA was detected in maternal blood, fetal blood and placental tissue; and actual
      concentrations of BPA were determined. Interestingly, significant accumulation of
      BPA in the placentas of women with preeclampsia compared to normotensive women
      has been shown. CONCLUSIONS: This is the first study to highlight a significant
      correlation between preeclampsia and a high accumulation of BPA in the placenta.

PMID- 24724920
TI  - African American adolescents and mental health care: a metasynthesis.
AB  - PROBLEM: African American adolescents access mental health services at lower
      rates than their Caucasian counterparts, thus resulting in a large disparity. The
      purpose of the study was to understand the experiences of African American
      adolescents in dealing with mental health conditions and what led to or hindered
      their access to mental health services. METHODS: A metasynthesis of six
      qualitative studies was conducted using the meta-ethnographic approach by Noblit
      and Hare. FINDINGS: Four reciprocal themes illuminating the experiences of
      African American adolescents with mental health issues were revealed: uncertainty
      and soul searching, strength of the inner circle, shame and reluctance, belief in
      the system. Each of the themes was explored in detail through the rich quotations
      of the adolescents. CONCLUSIONS: The findings provided an insight and
      understanding into the process the adolescents went through before seeking help
      and may aid as a framework for designing interventions to better serve this
      vulnerable population.

PMID- 24724921
TI  - Palladium-catalyzed direct arylation of 5-halouracils and 5-halouracil
      nucleosides with arenes and heteroarenes promoted by TBAF.
AB  - The 1-N-benzyl-5-iodo(or bromo)uracil undergoes Pd-catalyzed [Pd2(dba)3] direct
      arylation with benzene and other simple arenes in the presence of TBAF in DMF
      without the necessity of adding any ligands or additives to give 5-arylated
      uracil analogues. The TBAF-promoted coupling also occurs efficiently with
      electron rich heteroarenes at 100  degrees C (1 h) even with only small excess of
      heteroarenes. The protocol avoids usage of the arylboronic acid or stannane
      precursors for the synthesis of 5-(2-furyl, or 2-thienyl, or 2-pyrrolyl)uracil
      nucleosides, which are used as important RNA and DNA fluorescent probes. The fact
      that 1-N-benzyl-3-N-methyl-5-iodouracil did not undergo the TBAF-promoted
      couplings with arenes or heteroarenes suggests that the C4-alkoxide (enol form of
      uracil) facilitates coupling by participation in the intramolecular processes of
      hydrogen abstraction from arenes. TBAF-promoted arylation was extended into the
      other enolizable heterocyclic systems such as 3-bromo-2-pyridone. The pi
      excessive heteroarenes also coupled with 5-halouracils in the presence of
      Pd(OAc)2/Cs2CO3/PivOH combination in DMF (100  degrees C, 2 h) to yield 5
      arylated uracils. 

PMID- 24724922
TI  - Hypertrophic pyloric stenosis in twins; genetic or environmental factors.
AB  - The etiology of infantile hypertrophic pyloric stenosis (IHPS) remains obscure.
      Over 120 years after the condition has become a clinical entity the debate
      whether the cause of IHPS is genetic, environmental or both, has not yet reached
      a final conclusion. Herein, we present a pair of monozygotic male twins with IHPS
      together with a review of the literature. We aimed to support genetic pre
      disposition in the epidemiology of IHPS, adding a twin data to the literature and
      to review the associated articles about the pathogenesis and inheritance
      patterns. 

PMID- 24724923
TI  - Sleep-disordered breathing in children with cardiomyopathy.
AB  - RATIONALE: Cardiomyopathy is a rare condition in children that is associated with
      high mortality. Although sleep-disordered breathing is prevalent, its frequency
      and patterns in children with cardiomyopathy are unknown. OBJECTIVES: To evaluate
      the frequency and patterns of sleep-disordered breathing and their relationship
      to cardiac function in children with primary cardiomyopathy. METHODS: This study
      comprised a prospective, uncontrolled case series. Children with cardiomyopathy
      completed a sleep questionnaire, overnight polysomnography, blood pressure
      monitoring, otolaryngological assessment, and transthoracic echocardiography at
      the Hospital for Sick Children in Toronto, Canada. MEASUREMENTS AND MAIN RESULTS:
      Twenty-one patients (17 males) were recruited. The median age of the patients was
      10.7 years, and the median body mass index z score was 0.8. Sleep-disordered
      breathing was observed in 10 (48%) of 21 patients. Significant central sleep
      apnea was the main finding in 5 (24%) of 21 of the cohort and in 50% of the sleep
      disordered breathing population. The left ventricular end diastolic volume index
      was greater in children with central sleep apnea than in children without sleep
      disordered breathing (P = 0.03). There were significant correlations between the
      central apnea-hypopnea index and both left ventricular end diastolic and end
      systolic volume indexes (Spearman's r = 0.55, P = 0.01; Spearman's r = 0.47, P =
      0.03, respectively). Snoring, sleep architecture, blood pressure, and
      otolaryngological findings were not significantly different between children with
      sleep-disordered breathing versus those without sleep-disordered breathing.
      CONCLUSIONS: Sleep-disordered breathing is common in children with
      cardiomyopathy. In our present study, 24% of participants exhibited primarily
      central sleep apnea. The severity of cardiac dysfunction, as measured by left
      ventricular end diastolic volume index and left ventricular end systolic volume
      index, is associated with central sleep apnea. Longitudinal research is necessary
      to better characterize sleep disorders and their impact on cardiac function in a
      large pediatric cardiomyopathy population.

PMID- 24724925
TI  - Oscillating friction on shape-tunable wrinkles.
AB  - Friction on soft materials is strongly correlated with the associated
      deformation, which may be controlled by the surface topography. We investigate
      the wearless sliding friction between a rigid hemispherical indenter and a
      deformable textured surface, which is shape-tunable wrinkles. The size of the
      indenter is comparable to the wavelength of the wrinkles. We evaluate the effects
      on the friction of the aspect ratio of the wrinkles, the applied normal load, and
      the alignment direction of the wrinkles relative to the sliding direction. The
      frictional oscillations are observed during sliding in the direction
      perpendicular to the alignment using optical images and friction profiles. The
      correlation of friction force oscillation with deformation of the wrinkles is
      elucidated using Hertz contact theory. Within a cycle of frictional oscillation,
      the friction force increases as the front part of the indenter elastically plows
      the crests. When the normal load is high and/or the aspect ratio of the wrinkles
      is low, the indenter continues to squash the wrinkles and remains in contact with
      them during sliding. Consequently, the amplitude of friction force oscillation
      relative to the averaged friction force decreases. 

PMID- 24724926
TI  - Strained cycloalkynes as new protein sulfenic acid traps.
AB  - Protein sulfenic acids are formed by the reaction of biologically relevant
      reactive oxygen species with protein thiols. Sulfenic acid formation modulates
      the function of enzymes and transcription factors either directly or through the
      subsequent formation of protein disulfide bonds. Identifying the site, timing,
      and conditions of protein sulfenic acid formation remains crucial to
      understanding cellular redox regulation. Current methods for trapping and
      analyzing sulfenic acids involve the use of dimedone and other nucleophilic 1,3
      dicarbonyl probes that form covalent adducts with cysteine-derived protein
      sulfenic acids. As a mechanistic alternative, the present study describes highly
      strained bicyclo[6.1.0]nonyne (BCN) derivatives as concerted traps of sulfenic
      acids. These strained cycloalkynes react efficiently with sulfenic acids in
      proteins and small molecules yielding stable alkenyl sulfoxide products at rates
      more than 100* greater than 1,3-dicarbonyl reagents enabling kinetic competition
      with physiological sulfur chemistry. Similar to the 1,3-dicarbonyl reagents, the
      BCN compounds distinguish the sulfenic acid oxoform from the thiol, disulfide,
      sulfinic acid, and S-nitrosated forms of cysteine while displaying an acceptable
      cell toxicity profile. The enhanced rates demonstrated by these strained alkynes
      identify them as new bioorthogonal probes that should facilitate the discovery of
      previously unknown sulfenic acid sites and their parent proteins. 

PMID- 24724927
TI  - A psychometric evaluation of the Swedish version of the Responses to Positive
      Affect questionnaire.
AB  - BACKGROUND: Previous research mainly focused on responses to negative affect in
      relation to depression, and less on responses to positive affect. Cognitive
      responses to positive affect are interesting in the context of emotion regulation
      and emotion disorders: positive rumination is associated to hypomania risk and
      bipolar disorder. There is to date no questionnaire in Swedish that captures the
      phenomena of cognitive response styles. AIMS: The aim of this study was to
      investigate the replicability of the Responses to Positive Affect questionnaire
      (RPA) in a newly translated Swedish version and to test its psychometric
      properties. METHODS: Swedish undergraduates (n = 111) completed a set of self
      report questionnaires in a fixed order. RESULTS: The hypothesized three-factor
      model was largely replicated in the subscales Self-focused positive rumination,
      Emotion-focused positive rumination and Dampening. The two positive rumination
      subscales were strongly associated with each other and current positive affect.
      The subscales showed acceptable convergent and incremental validity with
      concurrent measures of depression, hypomania, anxiety, repetitive negative
      thinking, and positive and negative affect. The model explained 25% of the
      variance in hypomania, but fell short in the explanation of depression.
      CONCLUSIONS: The Swedish version of the RPA shows satisfactory reliability and
      initial findings from a student sample indicate that it is a valid measure
      comparable with the original RPA questionnaire. RESULTS give emphasis to the
      importance of further exploration of cognitive response styles in relation to
      psychopathology.

PMID- 24724928
TI  - Saliva testosterone and cortisol in male depressive syndrome, a community study.
      The Sudurnesjamenn Study.
AB  - INTRODUCTION: The association between testosterone levels and depression is
      unclear. The relationship has been described as complex, i.e. more U (J)-shaped
      than linear in some previous studies. AIM: The primary aim of this study was to
      examine the relationship between saliva testosterone level variations and
      different levels of male depressive symptoms in a community sample. The secondary
      aim was to investigate whether simultaneous testing of evening cortisol and
      testosterone improved the detection of depression. METHODS: In a community study,
      534 males were screened, using the Beck Depression Inventory (BDI), the Gotland
      Male Depression Scale (GMDS) and the Montgomery-Asberg Depression Rating Scale
      (MADRS). Those with signs of depression (n = 65) and randomly selected controls
      (n = 69) had psychiatric evaluation for depressive disorder. In a sub-sample (n =
      51) saliva testosterone was measured twice on a single day. RESULTS: Testosterone
      morning values were significantly higher than evening values (236 vs. 145 pg/ml,
      P = 0.009). Evening testosterone was significantly higher in depressive males,
      according to both MADRS (P = 0.028) and BDI (P = 0.036). Having depression
      increased the likelihood of being in the highest third of testosterone levels
      (BDI P = 0.021; MADRS P = 0.018). Positive correlation was between total BDI
      score and elevated evening testosterone with and without psychotropics (P =
      0.017; P = 0.002). Correlation was between elevated evening cortisol and evening
      testosterone levels (P = 0.021) though simultaneous testing did not increase
      specificity of detecting depression. CONCLUSION: Evening saliva testosterone
      measurements seem the most informative, as they correlate with male depressive
      syndrome. Simultaneous testing for evening cortisol and evening testosterone
      levels did not increase specificity for clinical diagnosis of depressive
      disorder.

PMID- 24724929
TI  - Is the PANSS cognitive scale measuring cognition?
AB  - OBJECTIVE: To investigate the association between the Positive and Negative
      Syndrome Scale (PANSS) cognitive factors and cognition assessed by
      neuropsychological tests. METHOD: Ninety patients with a psychotic illness, the
      majority having a schizophrenia diagnosis, were assessed with PANSS ratings and
      tested by a comprehensive computerized neuropsychological test battery, EuCog.
      RESULTS: Test performance was in the normal range for some of the cognitive
      indices, but substantially reduced for others, compared with norms, particularly
      speed-based indices. PANSS ratings were non-specifically associated with
      cognitive indices representing performance (speed and accuracy) and problem
      solving strategies (executive functions). There was no discriminant validity for
      the cognitive factor. A regression analysis suggested that the PANSS cognitive
      factors reflected verbal IQ but no other cognitive domain like memory, attention
      or speed. CONCLUSION: Cognitive test performance is associated with
      psychopathology as assessed by PANSS items but in a non-specific way. The PANSS
      cognitive subscale seems to reflect over-learned verbal skills rather than the
      cognitive domains, which are known to be specifically affected in schizophrenia
      and relevant for the prognosis. Consequently, PANSS ratings cannot replace the
      information inherent in neuropsychological test data. The extensive speed problem
      of patients with schizophrenia should be studied in more detail using test
      batteries that focus on that problem.

PMID- 24724930
TI  - Advancing our quantitative understanding of radiotherapy normal tissue morbidity.

PMID- 24724931
TI  - Manual positive pressure ventilation and the Copenhagen poliomyelitis epidemic
      1952: An attempt at setting the record straight.

PMID- 24724933
TI  - The complete mitochondrial genome of the Pazala timur (Lepidoptera: Papilionidae:
      Papilioninae).
AB  - The complete mitochondrial genome of Pazala timur (Lepidoptera: Papilionodae) is
      a circular molecule of 15,226 bp in length, containing 37 typical animal
      mitochondrial genes: 13 protein coding genes, 2 rRNA genes, 22 tRNA genes and a
      non-coding AT-rich region. Its gene order and arrangement are identical to all
      other available butterfly mitogenomes. All PCGs initiate with typical ATN codons,
      except for COI, which is initiated by the CGA codon. Ten PCGs use complete
      termination codon (TAA), whereas the COI, COII and ND5 genes end with single T.
      Twelve intergenic spacers (82 bp in total), and 11 overlapping regions (30 bp in
      total) are dispersed throughout the whole genome. The non-coding AT-rich region
      is 403 bp long and contains some conserved structures characteristic of the
      butterfly mitogenomes, such as the motif ATAGA followed by a 13-bp poly-T stretch
      and a microsatellite-like (AT)12 element preceded by the ATTTA motif.

PMID- 24724934
TI  - DNA barcoding using skin exuviates can improve identification and biodiversity
      studies of snakes.
AB  - Snakes represent a taxonomically underdeveloped group of animals in India with a
      lack of experts and incomplete taxonomic descriptions being the main deterrents
      to advances in this area. Molecular taxonomic approaches using DNA barcoding
      could aid in snake identification as well as studies of biodiversity. Here a non
      invasive sampling method using DNA barcoding is tested using skin exuviates.
      Taxonomically authenticated samples were collected and tested for validation and
      comparisons to unknown snake exuviate samples. This approach was also used to
      construct the first comprehensive study targeting the snake species from
      Maharashtra state in India. A total of 92 skin exuviate samples were collected
      and tested for this study. Of these, 81 samples were successfully DNA barcoded
      and compared with unknown samples for assignment of taxonomic identity. Good
      quality DNA was obtained irrespective of age and quality of the exuviate
      material, and all unknown samples were successfully identified. A total of 23
      species of snakes were identified, six of which were in the list of Endangered
      species (Red Data Book). Intra- and inter-specific distance values were also
      calculated, and these were sufficient to allow discrimination among species and
      between species without ambiguity in most cases. Two samples were suspected to
      represent cryptic species based on deep K2P divergence values (>3%), and one
      sample could be identified to the genus level only. Eleven samples failed to
      amplify COI sequences, suggesting the need for alternative PCR primer pairs. This
      study clearly documents how snake skin exuviates can be used for DNA barcoding,
      estimates of diversity and population genetic structuring in a noninvasive
      manner. 

PMID- 24724935
TI  - Mitochondrial genome architecture of the giant red sea urchin Mesocentrotus
      franciscanus (Strongylocentrotidae, Echinoida).
AB  - The complete mitochondrial genome of the Californian giant red sea urchin
      Mesocentrotus franciscanus has been determined. It has a length of 15,650 bp and
      contains the same 37 genes found in other metazoans (13 protein-coding genes, 22
      tRNA genes, and two rRNA genes). Only five tRNA genes and the Nad6 gene are coded
      on the minus strand. There were 14 identified small intergene regions (2 to 24
      bp) and a large non-coding region (125 bp) located between the tRNA-T and tRNA-P.
      The overall base composition of this genome is 29.8% A, 27.6% T, 29.7% C, and
      17.5% G, with a slight A + T bias of 59.4%. The most frequent start codon is ATG
      (11 genes) whereas TAA is the most frequent stop codon (10 genes). Overall, gene
      arrangement pattern, gene content and genome organization is similar to other
      echinoids.

PMID- 24724936
TI  - The "fast" and the "slow" modes of mitochondrial DNA degradation.
AB  - In a living cell, oxidative stress resulting from an external or internal insult
      can result in mitochondrial DNA (mtDNA) damage and degradation. Here, we show
      that in HeLa cells, mtDNA can withstand relatively high levels of extracellular
      oxidant H2O2 before it is damaged to a point of degradation, and that mtDNA
      levels in these cells quickly recover after removal of the stressor. In contrast,
      mtDNA degradation in mouse fibroblast cells is induced at eight-fold lower
      concentrations of H2O2, and restoration of the lost mtDNA proceeds much slower.
      Importantly, mtDNA levels in HeLa cells continue to decline even after withdrawal
      of the stressor thus marking the "slow" mode of mtDNA degradation. Conversely, in
      mouse fibroblasts maximal loss of mtDNA is achieved during treatment, and is
      already detectable at 5 min after exposure, indicating the "fast" mode. These
      differences may modulate susceptibility to oxidative stress of those organs,
      which consist of multiple cell types.

PMID- 24724937
TI  - 4,5-Dicyano-3,6-diethylbenzo-1,2-diselenete, a highly stable 1,2-diselenete: its
      preparation, structural characterization, calculated molecular orbitals, and
      complexation with tetrakis(triphenylphosphine)palladium.
AB  - The first isolable benzo-1,2-diselenete, 4,5-dicyano-3,6-diethylbenzo-1,2
      diselenete (4), was prepared by the reaction of 4,5-(o-xylylenediseleno)-3,6
      diethylphthalonitrile (3) with aluminum chloride in toluene. X-ray
      crystallographic analysis demonstrated that 4 contains a trapezoidal diselenide
      ring rather than a benzo-1,2-diselenone structure. In crystal form, 4 undergoes
      self-assembly and generates structures based on layered molecular sheets since
      the unit cell contains only one molecule. While the cyclic voltammogram of 4
      exhibited only one irreversible peak (Ep = 1.59 V) during oxidation and two
      quasireversible couples during reduction, three peaks were observed in the
      differential pulse voltammogram of the reduction couples (E1/2 = -1.19, -0.75,
      and -0.69 V). Although a THF solution of 4 in the presence of sodium metal was
      EPR silent, various signals were readily observed in its (1)H, (13)C, and (77)Se
      NMR spectra. Molecular orbital calculations for 4 demonstrated that the HOMO
      orbital is primarily localized at the two selenium atoms and four of the benzene
      carbon atoms while the LUMO orbital is situated solely on the diselenete ring. It
      appears that the HOMO and LUMO orbitals of 4 receive significant stabilization
      from the nitrile groups compared to the level of stabilization in the
      unsubstituted benzo-1,2-diselenete (BDS). The reaction of 4 with
      tetrakis(triphenylphosphine)palladium in benzene was found to produce a dinuclear
      palladium complex (8), and the structure of this complex was determined by X-ray
      crystallographic analysis. The central four membered ring of 8 consists of the
      Pd1, Se2, Pd2, and Se3 atoms and is not planar but rather adopts a folded
      arrangement. 

PMID- 24724939
TI  - Intrauterine therapy in a fetus with congenital dyserythropoietic anaemia type I.

PMID- 24724940
TI  - Learning from conservation planning for the U.S. National Wildlife Refuges.
AB  - The U.S. National Wildlife Refuge System has nearly completed its first round of
      unit-level, comprehensive conservation plans (CCPs) and will soon begin required
      revisions. Laws and policies governing refuge planning emphasize ecological
      integrity, landscape-scale conservation, and adaptive management. We evaluated
      185 CCPs completed during 2005-2011, which cover 324 of 555 national wildlife
      refuges. We reviewed CCP prescriptions addressing 5 common conservation issues
      (habitat and game, nongame, imperiled, and invasive species) and 3 specialized
      topics (landscape-scale conservation, climate change, and environmental quality).
      Common conservation issues received prescriptions in >90% of CCPs. Specialized
      topics received more variable treatment. Prescriptions for aquatic connectivity,
      water quantity, and climate-change impacts increased over the study period.
      Except for climate change, direct actions were the most common type of management
      prescription, followed by plans or studies. Most CCPs stated a commitment to
      adaptive management and prescribed monitoring for common conservation objectives;
      other aspects of planning for adaptive management were often lacking, despite
      strong support for adaptive management in the conservation planning literature.
      To better address refuge-specific threats, we recommend that revised plans
      explicitly match identified refuge issues with prescriptions, particularly for
      under-represented concerns such as novel pests and pathogens. We recommend
      incorporating triggers into monitoring frameworks and specifying actions that
      will occur when threshold values are reached to improve support for adaptive
      management. Revised CCPs should better reflect work that refuges already
      undertake to extend conservation objectives beyond their borders and better
      engage with regional conservation efforts to continue this work. More thorough
      landscape-scale threat assessments and explicit prioritization of planned actions
      would further improve conservation effectiveness. Excellent examples of all
      recommended practices exist within the CCPs we examined; sharing best planning
      practices would improve planning efficiency within the refuge system.

PMID- 24724941
TI  - Public databases of plant natural products for computational drug discovery.
AB  - Plant natural products have been intensively investigated during the past decades
      with a considerable amount of generated data. Databases are subsequently
      developed to facilitate the management and analysis of accumulated information
      including plant species, chemical compounds, structures and bioactivities. With
      the support of databases, the screening of novel bioactivities for plant natural
      products can benefit from advanced computational methods to accelerate the
      progress of drug discovery. This overview describes the contents of publicly
      available databases useful for computational research of plant natural products.
      Based on the databases, quantitative structure-activity relationship models and
      protein-ligand docking methods can be developed and applied to analyze and screen
      bioactive compounds. More public and structured databases with unique contents,
      search functions and links to major databases are needed for efficiently
      exploring the chemical space of plant natural products. 

PMID- 24724942
TI  - The transplant journey: psychosocial aspects of the different stages of the
      transplantation process.

PMID- 24724943
TI  - Tolerance of intraoperative hemoglobin decrease during cardiac surgery.
AB  - BACKGROUND: It has been suggested that a decrease of at least 50% from the
      preoperative hemoglobin (Hb) level during cardiac surgery is associated with
      adverse outcomes even if the absolute Hb level remains above the commonly used
      transfusion threshold of 7.0 g/dL. In this study the relation between
      intraoperative Hb decline of at least 50% and a composite endpoint was analyzed.
      STUDY DESIGN AND METHODS: This single-center study comprised 11,508 patients who
      underwent cardiac surgery and had normal preoperative Hb levels (12.0-16.0 g/dL
      in women, 13.0-18.0 g/dL in men) between January 2001 and December 2011. Logistic
      regression modeling was used. The composite endpoint comprised in-hospital
      mortality, stroke, myocardial infarction, and renal failure. RESULTS: Patients
      whose Hb did not decrease at least 50% and remained above 7 g/dL were used as
      reference (n = 9672). A total of 363 (3.2%) patients had an intraoperative Hb of
      less than 7 g/dL during surgery but a Hb decrease of less than 50%; 876 patients
      (7.4%) showed both a nadir Hb less than 7 g/dL and a Hb decrease of at least 50%,
      while 597 (5.2%) had a Hb decrease of at least 50% and a nadir Hb of at least 7
      g/dL. In this last group the incidence of the composite endpoint was higher than
      in patients in the reference group (adjusted odds ratio, 1.27; 95% confidence
      interval, 1.14-1.41). CONCLUSIONS: Our findings show that a decrease of at least
      50% from baseline Hb during cardiac surgery is associated with adverse outcomes,
      even if the absolute Hb level remains higher than the commonly used transfusion
      threshold of 7.0 g/dL.

PMID- 24724944
TI  - Pentafluorosulfanyldifluoroacetic acid: rebirth of a promising building block.
AB  - Three novel, easily scalable routes for the synthesis of
      pentafluorosulfanyldifluoroacetic acid, SF5CF2C(O)OH, are described. Reactions of
      its acid chloride with amines and alcohols led to a small library of 15 amides
      and five esters, respectively. The reaction of the acid chloride with
      phenylmagnesium bromide gave the corresponding acetophenone.
      Pentafluorosulfanyldifluoroacetonitrile was obtained from
      pentafluorosulfanyldifluoroacetamide by dehydration with diphosphorus pentoxide. 

PMID- 24724945
TI  - Reproductive isolation between two darter species is enhanced and asymmetric in
      sympatry.
AB  - Robust reproductive isolation was found between the rainbow darter Etheostoma
      caeruleum and the orangethroat darter Etheostoma spectabile, as more offspring
      were produced when conspecific males and females were crossed as compared with
      heterospecific crosses. Furthermore, fewer eggs resulted from heterospecific
      crosses involving sympatric E. spectabile females than those using allopatric E.
      spectabile females, while a similar pattern was not observed in heterospecific
      crosses using E. caeruleum females. These results suggest that reinforcement,
      i.e. selection for pre-zygotic reproductive barriers driven by reduced hybrid
      fitness, may have contributed to the evolution and maintenance of reproductive
      barriers between these potentially hybridizing species in sympatry. 

PMID- 24724938
TI  - Improving industrial yeast strains: exploiting natural and artificial diversity.
AB  - Yeasts have been used for thousands of years to make fermented foods and
      beverages, such as beer, wine, sake, and bread. However, the choice for a
      particular yeast strain or species for a specific industrial application is often
      based on historical, rather than scientific grounds. Moreover, new
      biotechnological yeast applications, such as the production of second-generation
      biofuels, confront yeast with environments and challenges that differ from those
      encountered in traditional food fermentations. Together, this implies that there
      are interesting opportunities to isolate or generate yeast variants that perform
      better than the currently used strains. Here, we discuss the different strategies
      of strain selection and improvement available for both conventional and
      nonconventional yeasts. Exploiting the existing natural diversity and using
      techniques such as mutagenesis, protoplast fusion, breeding, genome shuffling and
      directed evolution to generate artificial diversity, or the use of genetic
      modification strategies to alter traits in a more targeted way, have led to the
      selection of superior industrial yeasts. Furthermore, recent technological
      advances allowed the development of high-throughput techniques, such as 'global
      transcription machinery engineering' (gTME), to induce genetic variation,
      providing a new source of yeast genetic diversity. 

PMID- 24724946
TI  - Urinary lysosomal enzyme excretion in pregnant women with hypertensive disorders.
AB  - BACKGROUND: The authors assessed proximal renal tubular dysfunction and/or damage
      in pregnant women with various types of hypertension by measuring the three
      urinary lysosomal enzyme levels: N-acetyl-beta-d-glucosaminidase (NAG),
      arylsulfatase A and beta-glucuronidase. METHODS: The study consisted of 120
      pregnant women divided into four groups: 41 women in 20th week of gestation or
      more, with pregnancy-induced hypertension (PIH group), 28 pregnant women after 20
      weeks of pregnancy with pre-eclampsia (PE group), 21 pregnant women with chronic
      hypertension, identified before 20th week of pregnancy (CH group) and 30 healthy,
      pregnant women (healthy controls (HC) group). RESULTS: Statistical analysis
      showed significantly higher levels of all the three of lysosomal enzymes in the
      urine of patients with PE compared with the healthy pregnant women, pregnant
      women with PIH and the ones with chronic hypertension. Additionally,
      significantly higher values of NAG were found in the group of pregnant women with
      PIH compared with healthy pregnancies. No correlation was found between the
      concentration of enzymes in urine and values of blood pressure in any of the
      analyzed groups of pregnant women. CONCLUSIONS: The authors conclude that higher
      values of all the studied enzymes in PE group, in the comparison with the other
      groups, indicate proximal tubular damage at the cellular level. The lack of
      correlation between the concentration of lysosomal enzymes and blood pressure
      suggests that the damage to these parts of kidney is complex. In addition,
      mechanisms other than hypertension realizing intracellular enzymes may be
      involved in this process.

PMID- 24724947
TI  - Internet gaming and addiction: a reply to King & Delfabbro.

PMID- 24724961
TI  - Palladium-catalyzed benzylation of arylboronic acids with N,N
      ditosylbenzylamines.
AB  - The palladium-catalyzed coupling of N,N-ditosylbenzylamines with arylboronic
      acids has been investigated, and the resulting diarylmethanes were obtained in
      high yields. Conversion of the amine to a N,N-ditosylimide group provided an
      efficient leaving group for the Pd-catalyzed benzylation of arylboronic acids. 

PMID- 24724948
TI  - Genetic polymorphisms in the prostaglandin pathway genes and risk of head and
      neck cancer.
AB  - OBJECTIVE: Previous studies examining the association between genetic variations
      in prostaglandin pathway and risk of head and neck cancer (HNC) have only
      included polymorphisms in the PTGS2 (COX2) gene. This study investigated the
      association between genetic polymorphisms of six prostaglandin pathway genes
      (PGDS, PTGDS, PTGES, PTGIS, PTGS1 and PTGS2), and risk of HNC. METHODS:
      Interviews regarding the consumption of alcohol, betel quid, and cigarette were
      conducted with 222 HNC cases and 214 controls. Genotyping was performed for 48
      tag and functional single-nucleotide polymorphisms (SNPs). RESULTS: Two tag SNPs
      of PTGIS showed a significant association with HNC risk [rs522962: log-additive
      odds ratio (OR) = 1.42, 95% confidence interval (CI): 1.01-1.99 and dominant OR =
      1.58, 95% CI: 1.02-2.47; rs6125671: log-additive OR = 1.49, 95% CI: 1.08-2.05 and
      dominant OR = 1.96, 95% CI: 1.16-3.32]. In addition, a region in PTGIS tagged by
      rs927068 and rs6019902 was significantly associated with risk of HNC (global P =
      0.007). Finally, several SNPs interacted with betel quid and cigarette to
      influence the risk of HNC. CONCLUSIONS: Genetic variations in prostaglandin
      pathway genes are associated with risk of HNC and may modify the relationship
      between use of betel quid or cigarette and development of HNC.

PMID- 24724962
TI  - Solid lipid micro-dispersions (SLMs) based on PEGylated solidified reverse
      micellar solutions (SRMS): a novel carrier system for gentamicin.
AB  - The purpose of this study was to formulate and evaluate novel PEGylated
      solidified reverse micellar solutions (SRMS)-based solid lipid microparticles
      (SLMs) for improved delivery of gentamicin. Lipid matrix (SRMS) [consisting of
      15% w/w Phospholipon(r) 90G (P90G) in 35% w/w dika wax (Irvingia gabonensis) was
      formulated and characterized by differential scanning calorimetry (DSC). SLMs
      were formulated by melt-emulsification using the SRMS, PEG 4000 and gentamicin
      (1.0, 2.0, 3.0% w/w), and their physicochemical as well as pharmacokinetic
      parameters determined. In vitro permeation of gentamicin from the SLMs through
      artificial membrane (0.22 MUm pore size) was carried out using Franz's cell and
      phosphate-buffered saline (PBS, pH 7.4) as acceptor medium, while bioevaluation
      was performed using clinical isolates of Pseudomonas aeruginosa and
      Staphylococcus aureus. Stable and irregularly-shaped gentamicin-loaded SLMs of
      size range 34.49 +/- 2.56 to 53.52 +/- 3.09 um were obtained. The SLMs showed
      sustained drug permeation and exhibited time-dependent and capacity-limited
      bioactivity. Overall, SLMs containing 2% w/w SRMS, 3% w/w gentamicin and PEG 4000
      entrapped the highest amount of drug, gave highest IZD against the test organisms
      and highest permeation flux (5.239 MUg/cm(2).min) and permeation coefficient
      (1.781 * 10(-6)cm/min) within 420 min, while pure gentamicin gave the least.
      Preliminary in vivo pharmacokinetic studies also showed an AUC-24 of 1507 ug/h/ml
      for the optimized formulation, while that of oral drug solution was 678 ug/h/ml.
      This showed a 2.2-fold increase in the systemic bioavailability of gentamicin
      from the optimized formulation. PEGylated SRMS-based SLMs prepared with
      heterolipid from Irvingia gabonensis would likely offer a reliable delivery
      system for gentamicin.

PMID- 24724963
TI  - Preparation and evaluation of dl-praeruptorin A microemulsion based hydrogel for
      dermal delivery.
AB  - The purpose of the present investigation was to develop and optimize the
      microemulsion (ME) as a transdermal system for Pd-Ia, a poor water soluble and
      low bioavailable drug. The pseudo-ternary phase diagrams were constructed for
      various ME formulations including oleic acid as the oil phase, Cremophor RH40 as
      the surfactant, ethanol as the cosurfactant, and water. The maximum cumulative
      amount permeated through rat abdominal skins per unit area in 32 h (Q32), and the
      maximum flux were evaluated using the Franz diffusion cell in order to optimize
      the ME formulation. The results indicated that the optimized ME formulation was
      composed of oleic acid (5%, W/W), Cremophor RH40 (13.33%, W/W), ethanol (26.67%,
      W/W), and water (55%, W/W); the maximum cumulative amount of Pd-Ia was 354.330 +/
      12.006 MUg cm(-2), the maximum flux was 11.467 +/- 0.500 MUg cm(-2)h(-1). ME-gel
      was administered transdermally to rats. The mean plasma concentration of Pd-Ia
      following transdermal application of ME-gel could be maintained for 32 h at least
      and the half-life was evidently prolonged. It shows that the ME-gel could be a
      promising vehicle for dermal delivery of Pd-Ia.

PMID- 24724964
TI  - Findings from the implementation of a validated readmission predictive tool in
      the discharge workflow of a medical intensive care unit.
AB  - RATIONALE: Provider decisions about patients to be discharged from the intensive
      care unit (ICU) are often based on subjective intuition, sometimes leading to
      premature discharge and early readmission. The Stability and Work Load Index for
      Transfer (SWIFT) score, as a risk stratification tool, has moderate ability to
      predict patients at risk of ICU readmission. OBJECTIVES: To describe findings
      following the incorporation of the SWIFT score into the discharge workflow of a
      medical ICU. METHODS: The study involved 5,293 consecutive patients discharged
      alive from the medical ICU of an academic medical center. The SWIFT score and
      associated percentage risk for readmission were incorporated into daily rounds
      for purpose of discharge decision-making. We measured readmission rates before
      and after implementation and observed changes in provider discharge decisions for
      individual patients after SWIFT discussions. MEASUREMENTS AND MAIN RESULTS:
      Baseline (n = 1,906) and implementation (n = 1,938) cohorts differed with respect
      to APACHE III scores (P = 0.03). In the implementation cohort, 26.2% of subjects
      had SWIFT scores greater than 15 and thus were predicted to have a higher risk of
      unplanned readmissions. In this high-risk group, 25% had SWIFT discussed in their
      discharge planning. There was modification of provider discharge decisions in 108
      (30%) of cases in which the SWIFT was discussed. SWIFT score values above a
      prespecified cutoff of 15 were associated with physician tendency to prolong ICU
      stay or to discharge to a monitored setting (P < 0.001). There was no difference
      in 24-hour or 7-day readmission rates between the baseline and implementation
      cohorts (1.9 vs. 2.4%, P = 0.24; 6.5 vs. 7.4%, P = 0.26, respectively) even after
      adjustment for severity of illness. CONCLUSIONS: Using the SWIFT score as an
      adjunct to clinical judgment, physicians modified their discharge decisions in
      one-third of subjects. Introducing such tools into the discharge workflow may
      present change management challenges that limit the evaluation of their impact on
      readmission rates and other relevant ICU outcomes.

PMID- 24724965
TI  - Pharmacokinetics of dexmedetomidine combined with therapeutic hypothermia in a
      piglet asphyxia model.
AB  - BACKGROUND: The highly selective alpha2 -adrenoreceptor agonist, dexmedetomidine,
      exerts neuroprotective, analgesic, anti-inflammatory and sympatholytic properties
      that may be beneficial for perinatal asphyxia. The optimal safe dose for pre
      clinical newborn neuroprotection studies is unknown. METHODS: Following cerebral
      hypoxia-ischaemia, dexmedetomidine was administered to nine newborn piglets in a
      de-escalation dose study in combination with hypothermia (whole body cooling to
      33.5 degrees C). Dexmedetomidine was administered with a loading dose of 1 MUg/kg
      and maintenance infusion at doses from 10 to 0.6 MUg/kg/h. One additional piglet
      was not subjected to hypoxia-ischaemia. Blood for pharmacokinetic analysis was
      sampled pre-insult and frequently post-insult. A one-compartment linear
      disposition model was used to fit data. Population parameter estimates were
      obtained using non-linear mixed effects modelling. RESULTS: All dexmedetomidine
      infusion regimens led to plasma concentrations above those associated with
      sedation in neonates and children (0.4-0.8 MUg/l). Seven out of the nine piglets
      with hypoxia-ischaemia experienced periods of bradycardia, hypotension,
      hypertension and cardiac arrest; all haemodynamic adverse events occurred in
      piglets with plasma concentrations greater than 1 MUg/l. Dexmedetomidine
      clearance was 0.126 l/kg/h [coefficient of variation (CV) 46.6.%] and volume of
      distribution was 3.37 l/kg (CV 191%). Dexmedetomidine clearance was reduced by
      32.7% at a temperature of 33.5 degrees C. Dexmedetomidine clearance was reduced
      by 55.8% following hypoxia-ischaemia. CONCLUSIONS: Dexmedetomidine clearance was
      reduced almost tenfold compared with adult values in the newborn piglet following
      hypoxic-ischaemic brain injury and subsequent therapeutic hypothermia. Reduced
      clearance was related to cumulative effects of both hypothermia and exposure to
      hypoxia. High plasma levels of dexmedetomidine were associated with major
      cardiovascular complications.

PMID- 24724967
TI  - Beyond graphene: stable elemental monolayers of silicene and germanene.
AB  - Two-dimensional materials are one of the most active areas of nanomaterials
      research. Here we report the structural stability, electronic and vibrational
      properties of different monolayer configurations of the group IV elemental
      materials silicene and germanene. The structure of the stable configuration is
      calculated and for planar and low (<1 A) atomic buckling configurations, analysis
      of the electronic band structure reveals linear band dispersion giving rise to
      massless Dirac Fermions with a Fermi velocity about two-thirds that of graphene.
      Monolayer stability is shown to be directly attributed to the phonons present
      with the instability being driven by the out-of-plane ZA and ZO phonon modes.
      Long momentum relaxation lengths and high carrier mobilities are predicted for
      silicene and germanene based devices as carrier relaxation via phonon scattering
      is found to be inhibited as the electron-optical phonon coupling matrix elements
      are calculated to be small, being about a factor of 25 times smaller than in
      graphene. The consequences for phonon scattering, high energy electrical
      transport and integration of elemental monolayers into electronic devices are
      further discussed. 

PMID- 24724966
TI  - Phenotypic heterogeneity and mutational spectrum in a cohort of 45 Italian males
      subjects with X-linked ectodermal dysplasia.
AB  - Ectodermal dysplasias (EDs) are a group of genetic disorders characterized by the
      abnormal development of the ectodermal-derived structures. X-linked hypohidrotic
      ectodermal dysplasia, resulting from mutations in ED1 gene, is the most common
      form. The main purpose of this study was to characterize the phenotype spectrum
      in 45 males harboring ED1 mutations. The study showed that in addition to the
      involvement of the major ectodermal tissues, the majority of patients also have
      alterations of several minor ectodermal-derived structures. Characterizing the
      clinical spectrum resulting from ED1 gene mutations improves diagnosis and can
      direct clinical care. 

PMID- 24724968
TI  - Mechanism of photoinduced bending and twisting in crystalline microneedles and
      microribbons composed of 9-methylanthracene.
AB  - The solid-state photodimerization of 9-methylanthracene is used as a model system
      to investigate how crystal morphology and reaction dynamics affect
      photomechanical deformations of single microcrystals. By varying the
      crystallization conditions, two different crystal shapes, microneedles and
      microribbons, are grown on a clean water surface. The microribbons twist under
      irradiation, while the microneedles bend. In both shapes, the maximum deformation
      occurs at roughly the midpoint of the reaction, while further dimerization causes
      the crystals return to their original shapes. Powder X-ray diffraction patterns
      establish that the needles and ribbons have the same crystal orientation and that
      the photoreaction proceeds in a crystal-to-crystal manner. NMR spin-lattice
      relaxation measurements are consistent with the rapid formation of large (>100
      nm) dimer crystal domains. Simultaneous measurement of the needle bending and
      monomer fluorescence signal allows us to correlate the bending with the reaction
      progress. The behavior is qualitatively reproduced by a model in which the motion
      is driven by strain between spatially distinct reactant and product domains, also
      called heterometry. We consider several different mechanisms that could give rise
      to these spatially distinct domains. The ability to control the photoinduced
      crystal deformation by manipulating crystal shape and solid-state reaction
      kinetics suggests that photoreactive molecular crystals may be useful for
      generating well-defined motions on small length scales. 

PMID- 24724969
TI  - Inhibitor design strategy based on an enzyme structural flexibility: a case of
      bacterial MurD ligase.
AB  - Increasing bacterial resistance to available antibiotics stimulated the discovery
      of novel efficacious antibacterial agents. The biosynthesis of the bacterial
      peptidoglycan, where the MurD enzyme is involved in the intracellular phase of
      the UDP-MurNAc-pentapeptide formation, represents a collection of highly
      selective targets for novel antibacterial drug design. In our previous
      computational studies, the C-terminal domain motion of the MurD ligase was
      investigated using Targeted Molecular Dynamic (TMD) simulation and the Off-Path
      Simulation (OPS) technique. In this study, we present a drug design strategy
      using multiple protein structures for the identification of novel MurD ligase
      inhibitors. Our main focus was the ATP-binding site of the MurD enzyme. In the
      first stage, three MurD protein conformations were selected based on the obtained
      OPS/TMD data as the initial criterion. Subsequently, a two-stage virtual
      screening approach was utilized combining derived structure-based pharmacophores
      with molecular docking calculations. Selected compounds were then assayed in the
      established enzyme binding assays, and compound 3 from the aminothiazole class
      was discovered to act as a dual MurC/MurD inhibitor in the micomolar range. A
      steady-state kinetic study was performed on the MurD enzyme to provide further
      information about the mechanistic aspects of its inhibition. In the final stage,
      all used conformations of the MurD enzyme with compound 3 were simulated in
      classical molecular dynamics (MD) simulations providing atomistic insights of the
      experimental results. Overall, the study depicts several challenges that need to
      be addressed when trying to hit a flexible moving target such as the presently
      studied bacterial MurD enzyme and show the possibilities of how computational
      tools can be proficiently used at all stages of the drug discovery process. 

PMID- 24724970
TI  - Feto-maternal correlation of PTX3, sFlt-1 and PlGF in physiological and pre
      eclamptic pregnancies.
AB  - OBJECTIVE: PTX3, sFlt-1 and PlGF levels in maternal blood are altered in some
      obstetric diseases, such as preeclampsia (PE). Nonetheless, only few data on
      their expression in the fetal compartment have been reported so far. STUDY
      DESIGN: An observational study was performed by prospectively collecting maternal
      and fetal serum samples in 51 singleton pregnancies divided into two groups: 22
      PE women and 29 healthy controls. The relationships between maternal and fetal
      marker serum levels were evaluated by Spearman correlation. RESULTS: A feto
      maternal correlation was neither identified for PTX3 in either PE or control
      groups (1.1 versus 3.8 ng/ml, p = 0.17 and 0.9 versus 1.3 ng/ml, p = 0.30,
      respectively), nor for sFlt-1 and PlGF in healthy pregnancies (158.2 versus
      3326.0 pg/ml, p = 0.28 and 11.0 versus 230.9 pg/ml, p = 0.51). In contrast, PE
      patients showed a significant positive feto-maternal correlation for both sFlt-1
      and PlGF (324.1 versus 10 825.0 pg/ml and 7.8 versus 31.6 pg/ml, respectively, p
      = 0.02 for both markers). CONCLUSION: According to our results, an independent
      fetal production of the analyzed soluble angiogenic markers can be hypothesized
      in pregnancies complicated by PE.

PMID- 24724971
TI  - Enantioselective synthesis of an HCV NS5a antagonist.
AB  - A concise, enantioselective synthesis of the HCV NS5a inhibitor MK-8742 (1) is
      reported. The features of the synthesis include a highly enantioselective
      transfer hydrogenation of an NH imine and a dynamic diastereoselective
      transformation. The synthesis of this complex target requires simple starting
      materials and nine linear steps for completion. 

PMID- 24724972
TI  - Evolution of phenotypic plasticity and environmental tolerance of a labile
      quantitative character in a fluctuating environment.
AB  - Quantitative genetic models of evolution of phenotypic plasticity are used to
      derive environmental tolerance curves for a population in a changing environment,
      providing a theoretical foundation for integrating physiological and community
      ecology with evolutionary genetics of plasticity and norms of reaction.
      Plasticity is modelled for a labile quantitative character undergoing continuous
      reversible development and selection in a fluctuating environment. If there is no
      cost of plasticity, a labile character evolves expected plasticity equalling the
      slope of the optimal phenotype as a function of the environment. This contrasts
      with previous theory for plasticity influenced by the environment at a critical
      stage of early development determining a constant adult phenotype on which
      selection acts, for which the expected plasticity is reduced by the environmental
      predictability over the discrete time lag between development and selection. With
      a cost of plasticity in a labile character, the expected plasticity depends on
      the cost and on the environmental variance and predictability averaged over the
      continuous developmental time lag. Environmental tolerance curves derived from
      this model confirm traditional assumptions in physiological ecology and provide
      new insights. Tolerance curve width increases with larger environmental variance,
      but can only evolve within a limited range. The strength of the trade-off between
      tolerance curve height and width depends on the cost of plasticity. Asymmetric
      tolerance curves caused by male sterility at high temperature are illustrated. A
      simple condition is given for a large transient increase in plasticity and
      tolerance curve width following a sudden change in average environment. 

PMID- 24724973
TI  - Complete mitochondrial DNA genome of Pseudobagrus medianalis (Siluriformes:
      Bagridae).
AB  - The complete mitochondrial genome was sequenced from the freshwater fish,
      Pseudobagrus medianalis (Siluriformes: Bagridae) in this study. The genome
      sequence was 16,647 bp in length, and the gene order and contents were identical
      with the bagridae fishes. The mitochondrial genome contains 13 protein-coding
      genes, 2 ribosomal RNAs, 22 transfer RNAs and 2 non-coding regions (control
      region and origin of light-strand replication). All genes were encoded on the
      heavy strain except for ND6 and eight tRNA genes. The overall base composition is
      25.7% A, 30.9% T, 28.0% G, 15.4% C, with an A+T bias of 56.6%. The complete
      mitogenome data provides useful genetic markers for the studies on the molecular
      identification, population genetics, phylogenetic analysis and conservation
      genetics.

PMID- 24724974
TI  - Recombinant mitochondrial genome with standard transmission route from
      Mediterranean mussel Mytilus galloprovincialis.
AB  - Several bivalve species, including marine mussels Mytilus are atypical in having
      two gender-specific and highly divergent mtDNA genomes. This peculiar genetic
      system allows not only the recombination to occur but also facilitates its
      detection. Previous reports associated the existence of mosaic recombinant
      haplotypes with the switch of their transmission route. Here we report nearly
      complete sequence of a mitochondrial genome isolated from a homoplasmic female
      individual of Mediterranean Mytilus galloprovincialis. The genome has clear
      phylogenetic affinity with and organization identical to the M. galloprovincialis
      female haplotypes, in the coding part. However, the genome is very large,
      approximately 20,600 bp long, exclusively due to a long and complex control
      region. It contains an array of repeats, some of which are degenerated. A large
      part of the control region is derived from the paternal genome. This finding
      shows that not all haplotypes with recombinant control regions must be paternally
      inherited in Mytilus.

PMID- 24724975
TI  - Complete mitochondrial genome of the Chinese bitterling Acheilognathus
      macropterus (Cypriniformes: cyprinidae).
AB  - Acheilognathus macropterus belongs to the family Acheilognathinae. In the present
      study, we obtain the complete mitochondrial genome of the Chinese bitterling A.
      macropterus by PCR amplification and DNA sequencing. It is a circular double
      stranded DNA molecule of 16,773 bp in length, containing 13 protein-coding genes,
      22 transfer RNA genes, two ribosomal RNA genes, and two main non-coding regions
      (the control region and the origin of the light strand replication). The gene
      composition and order of which are similar to most other vertebrates. Compared
      with Acanthorhodeus macropterus, they share 98.90% nucleotide sequences
      similarity, and the biggest nucleotide sequence discrepancy between homologous
      genes are observed in ND5 gene. The molecular data we presented here could
      provide useful information for the studies on species identification,
      evolutionary relationships and population genetics of the Acheilognathinae.

PMID- 24724976
TI  - Population genetic diversity of the northern snakehead (Channa argus) in China
      based on the mitochondrial DNA control region and adjacent regions sequences.
AB  - Genetic variation and population structure of northern snakehead (Channa argus)
      from eight locations in China were investigated using mitochondrial DNA control
      region and adjacent regions sequences. Sequence analysis showed that there were
      105 haplotypes in 260 individuals, 48 unique haplotypes and 57 shared haplotypes,
      but no common haplotype shared by all populations. As a whole, the haplotype
      diversity was high (h=0.989), while the nucleotide diversity was low
      (pi=0.00482). AMOVA analysis detected significant genetic differentiation among
      all eight populations (FST=0.328, p<0.01) and 66.17% of the total variance was
      resulted from intra-population differentiation. UPGMA analysis indicated that the
      eight populations could be divided into four major clusters, which was consistent
      with that the eight sampled locations were belonged to four isolated river
      systems. The neutrality and mismatch distribution tests suggested that the eight
      populations of C. argus in the sampling locations underwent recent population
      expansion. Among the eight populations, the Erhai Lake population may represent a
      unique genetic resource and therefore needs to be conserved.

PMID- 24724977
TI  - Cytochrome b gene reveals panmixia among Japanese Threadfin Bream, Nemipterus
      japonicus (Bloch, 1791) populations along the coasts of Peninsular Malaysia and
      provides evidence of a cryptic species.
AB  - We evaluated genetic differentiation among ten presumed Japanese threadfin bream,
      Nemipterus japonicus populations along the coast of Peninsular Malaysia based on
      the partial sequence of the mitochondrial cytochrome b gene (982 bp). Genetic
      divergences (Kimura-2 parameter) ranged from 0.5% to 0.8% among nine of the ten
      populations while these nine populations were 4.4% to 4.6% diverged from the
      Kuala Besar population located at the Northeast coast. The constructed Neighbour
      Joining (NJ) phylogenetic trees based on haplotypes showed the Kuala Besar
      population forming an isolated cluster. The Analysis of Molecular Variance
      (AMOVA) of the ten populations a priori assigned into four regions, revealed that
      most of the variation occurred within population with a fairly low but
      significant level of regional differentiation (FST = 0.07, p < 0.05, FSC = 0.00,
      p > 0.05 and FCT = 0.07, p < 0.05) attributed to the Kuala Besar population. p
      Value after Bonferroni correction revealed that only pairwise FST values
      involving the Kuala Besar population with the other nine populations were
      significant. Thus, this study revealed that the N. japonicus populations off
      Peninsular Malaysia were panmictic. However, the Kuala Besar population, although
      morphologically identical was composed of a genetically discrete taxon from the
      rest. These findings are important contributions in formulating sustainable
      fishery management policies for this important fishery in Peninsular Malaysia.

PMID- 24724978
TI  - Downgrading, downsizing, degazettement, and reclassification of protected areas
      in Brazil.
AB  - Protected areas (PAs) are key elements for biodiversity conservation and
      ecosystem services. Brazil has the largest PA system in the world, covering
      approximately 220 million ha. This system expanded rapidly in the mid-1990s to
      the mid-2000s. Recent events in Brazil, however, have led to an increase in PA
      downgrading, downsizing, and degazettement (PADDD). Does this reflect a shift in
      the country's PA policy? We analyzed the occurrence, frequency, magnitude, type,
      spatial distribution, and causes of changes in PA boundaries and categories in
      Brazil. We identified 93 PADDD events from 1981 to 2012. Such events increased in
      frequency since 2008 and were ascribed primarily to generation and transmission
      of electricity in Amazonia. In Brazilian parks and reserves, 7.3 million ha were
      affected by PADDD events, and of these, 5.2 million ha were affected by
      downsizing or degazetting. Moreover, projects being considered by the Federal
      Congress may degazette 2.1 million ha of PA in Amazonia alone. Relaxing the
      protection status of existing PAs is proving to be politically easy in Brazil,
      and the recent increase in frequency and extension of PADDD reflects a change in
      governmental policy. By taking advantage of chronic deficiencies in financial and
      personnel resources and surveillance, disputes over land tenure, and the slowness
      of the Brazilian justice, government agencies have been implementing PADDD
      without consultation of civil society. If parks and reserves are to maintain
      their integrity, there will need to be investments in Brazilian PAs and a better
      understanding of the benefits PAs provide.

PMID- 24724979
TI  - One-step bulk synthesis of stable, near unit-cell sized oxide nanoparticles and
      nanoparticle blends using KO2.
AB  - Presented here is a novel one-step synthesis of oxide or hydroxide nanoparticles
      using, for the first time, potassium superoxide (KO2). This work demonstrates
      that the reaction of KO2 with different salt solutions produces grams of stable,
      near unit-cell sized nanoparticles. This new synthetic technique is applied to
      representative elements from across the periodic table to rapidly produce
      nanometer sized oxides or hydroxides of Mg, Al, Y, Ti, Mn, Fe, Co, Ni, Cu, Zn,
      Sn, Tl, Pb, and Ce. This technique is also used to produce blends of
      nanoparticles, demonstrating the ability to prepare complex materials such as
      nanoparticulate blends of a lithium cathode material (LiCoO2), the multiferroic
      compound (BiMnO(3+delta)), and the superconducting YBa2Cu3O(7-gamma).

PMID- 24724980
TI  - Salvelinus namaycush spawning substratum attracts egg predators and opportunists
      through chemosensory cues.
AB  - Two separate field experiments were conducted in a series of small boreal lakes
      to test for the attraction of egg predators to lake trout Salvelinus namaycush
      spawning shoals and subsequently to determine whether chemosensory cues attract
      egg predators to these sites. In the first experiment, minnow traps set on
      spawning sites captured significantly more egg predators than those set on
      structurally similar non-spawning sites. Captures of slimy sculpin Cottus
      cognatus, common shiner Luxilus cornutus, blacknose shiner Notropis heterolepis
      and virile crayfish Orconectes virilis were more than double on spawning sites
      relative to non-spawning sites for the two study lakes. To test whether
      chemosensory cues could attract egg predators to S. namaycush spawning sites,
      paired minnow traps were placed on eight to 10 sites in each of the three study
      lakes; one trap contained visually concealed S. namaycush spawning substratum and
      the other with visually concealed non-spawning substratum. Traps containing
      spawning substratum consistently captured more fish and had higher mean daily
      catches than those that contained non-spawning substratum. The combined results
      demonstrate a greater prevalence of egg predators on S. namaycush spawning shoals
      that appears to be the result of chemosensory attraction to spawning substratum. 

PMID- 24724982
TI  - Antimicrobial activity in cord blood units: occurrence and levels of antibiotics.
AB  - BACKGROUND: Antibiotic prophylaxis treatment at delivery is highly recommended
      for reducing the risk of infection for mothers positive for group B
      streptococcus. It is therefore expected that some cord blood (CB) products will
      contain residual antibiotics. This study aimed to determine the incidence and
      level of beta-lactam antibiotics in CB products. STUDY DESIGN AND METHODS: The
      antimicrobial activity of 60 CB plasma by-products was evaluated using disk
      diffusion assays on 10 bacteria species. Plasma samples showing antimicrobial
      activity were either treated with beta-lactamase enzyme to inhibit beta-lactam
      antibiotics or heated to 56 degrees C for 30 minutes to inhibit complement
      proteins. beta-Lactam antibiotic concentrations were determined by comparison
      with a standard curve obtained with known concentrations of antibiotics. RESULTS:
      Antimicrobial activity against mostly Gram-positive microorganisms was observed
      in 33% of CB units. The beta-lactamase enzyme abolished the antimicrobial
      activity in the majority of these CB products. Up to 5 MUg/mL penicillin and 14
      MUg/mL ampicillin were measured in these products. CONCLUSION: Approximately one
      third of CB products contain significant amounts of plasma with residual
      antibiotics, which can affect the survival and growth of bacterial contaminants
      when performing the sterility test and potentially lead to false-negative
      results. Additional work is required to better understand whether residual
      antibiotics in CB affect penicillin-allergic patients.

PMID- 24724981
TI  - Target identification of grape seed extract in colorectal cancer using drug
      affinity responsive target stability (DARTS) technique: role of endoplasmic
      reticulum stress response proteins.
AB  - Various natural agents, including grape seed extract (GSE), have shown
      considerable chemopreventive and anti-cancer efficacy against different cancers
      in pre-clinical studies; however, their specific protein targets are largely
      unknown and thus, their clinical usefulness is marred by limited scientific
      evidences about their direct cellular targets. Accordingly, herein, employing,
      for the first time, the recently developed drug affinity responsive target
      stability (DARTS) technique, we aimed to profile the potential protein targets of
      GSE in human colorectal cancer (CRC) cells. Unlike other methods, which can cause
      chemical alteration of the drug components to allow for detection, this approach
      relies on the fact that a drug bound protein may become less susceptible to
      proteolysis and hence the enriched proteins can be detected by Mass Spectroscopy
      methods. Our results, utilizing the DARTS technique followed by examination of
      the spectral output by LC/MS and the MASCOT data, revealed that GSE targets
      endoplasmic reticulum (ER) stress response proteins resulting in overall down
      regulation of proteins involved in translation and that GSE also causes oxidative
      protein modifications, specifically on methionine amino acids residues on its
      protein targets. Corroborating these findings, mechanistic studies revealed that
      GSE indeed caused ER stress and strongly inhibited PI3k-Akt-mTOR pathway for its
      biological effects in CRC cells. Furthermore, bioenergetics studies indicated
      that GSE also interferes with glycolysis and mitochondrial metabolism in CRC
      cells. Together, the present study identifying GSE molecular targets in CRC
      cells, combined with its efficacy in vast pre-clinical CRC models, further
      supports its usefulness for CRC prevention and treatment. 

PMID- 24724983
TI  - Sublingual misoprostol to decrease blood loss after caesarean delivery: a
      randomised controlled trial.
AB  - The aim of the study was to compare the efficacy of sublingual misoprostol in
      addition to intravenous oxytocin, with oxytocin alone, in reducing blood loss
      during and following caesarean section. A total of 120 women undergoing caesarean
      delivery at the University College Hospital, Ibadan, were randomised into two
      equal groups. In Group A, 20 IU of intravenous oxytocin was given after umbilical
      cord clamping, while in Group B, the women received 400 MUg misoprostol
      sublingually and 20 IU oxytocin intravenously. The outcome measures were blood
      loss, additional uterotonics, change in packed cell volume and side-effect
      profile. Associations between variables were determined by the chi(2) and
      Student's t-test. Relative risks were calculated for side-effects; the level of
      significance was p < 0.05. Intraoperative and postoperative blood loss were
      significantly lower in Group B (451.3 ml vs 551.2 ml, p = 0.007; 22.7 vs 42.2 ml,
      p < 0.001, respectively). In Group B, women were 7.4 (p < 0.001) and 9.0 (p =
      0.008) times more likely to experience shivering and fever, respectively. The
      need for additional uterotonics was greater in the oxytocin group (66.7% vs
      27.6%, p < 0.001). The addition of sublingual misoprostol to intravenous oxytocin
      reduces postpartum blood loss and the need for additional uterotonics. There is
      however, an increased risk of shivering and fever with this combination.

PMID- 24724984
TI  - Successful hematopoietic stem cell transplantation in a patient with congenital
      dyserythropoietic anemia type II.
AB  - CDA are a group of inherited, rare diseases that are characterized by
      dyserythropoiesis and ineffective erythropoiesis associated with transfusion
      dependency in approximately 10% of cases. For these latter patients, the only
      curative treatment is HSCT. There are very limited data on HSCT experience in
      this rare disease. Herein, we report a five-yr six-month-old girl with compound
      heterozygous mutations in SEC23B gene, who was diagnosed to have CDA type II and
      underwent successful HSCT from her matched sibling donor. 

PMID- 24724985
TI  - Radiation-induced oral mucositis and periodontitis--proposal for an inter
      relationship.

PMID- 24724986
TI  - Familial Himalayan p wave and left ventricular hypertrabeculation/noncompaction.
AB  - BACKGROUND: "Himalayan P waves," are reported in congenital heart disease and
      cardiomyopathies. METHODS: We report a family with hypertrophic cardiomyopathy,
      Himalayan P waves, extensive focal right atrial wall thickening and left
      ventricular hypertrabeculation/noncompaction (LVHT). RESULTS: The father received
      a pacemaker and underwent heart transplantation because of hypertrophic
      cardiomyopathy. His daughters showed Himalayan P waves and right atrial wall
      thickening. LVHT was diagnosed in sister A at age 23 years and developed in
      sister B between 42 and 46 years. In sister A the heart rate continuously
      declined. She refused implantation of a pacemaker and died with 49 years. Sister
      B, suffers from bradycardia. CONCLUSIONS: Himalayan P waves are due to focal
      right atrial wall thickening, may be familially and associated with LVHT.

PMID- 24724988
TI  - Cationic polymer-based micro-emulgel with self-preserving ability for transdermal
      delivery of diclofenac sodium.
AB  - The objective of the present study was to develop a topical preparation with
      enhanced skin permeation, high safety and self-preserving ability. Microemulsion
      (ME) and cationic polymer based micro-emulgel (CPBM) were investigated for the
      transdermal delivery of diclofenac sodium (DS). Medium-chain triglyceride was
      selected as the oil phase of ME due to its good solubilization of DS and high
      safety. Orthogonal test was applied to optimize the formula of ME based on the
      cumulative skin permeation amount in vitro after preliminary formula test.
      Chitosan (CS) or polylysine was employed as the cationic polymer in the formula
      of CPBM. The transdermal delivery of DS was evaluated through in vitro skin
      permeation test. The results showed that the skin permeation rate of DS from the
      optimized CPBM (126.17 +/- 15.82 MUg/cm(2)/h) were 1.86-folds and 5.76-folds
      higher than that of DS commercial Emulgel and DS control hydrogel, respectively.
      MEs and the cationic polymer were found to have skin penetration co-enhancing
      effect when they were combined in the CPBM system. Furthermore, the CPBM showed a
      good growth inhibition of E. coli and S. aureus. The stability test revealed that
      the CPBM was stable at room temperature and 4  degrees C for a period of three
      months.

PMID- 24724987
TI  - Psychosocial correlates of gender-based violence among HIV-infected and HIV
      uninfected women in three US cities.
AB  - Gender-based violence (GBV) is common among women with and at risk for HIV, yet
      little is known about the GBV associated psychological factors that could be
      modifiable through behavioral interventions. The current study examined the
      associations between some of these psychological factors (i.e., hopelessness,
      consideration of future consequences, self esteem), mental health symptoms,
      substance abuse, and GBV among a sample of 736 HIV-infected and
      sociodemographically similar uninfected participants in the Women's Interagency
      HIV Study (WIHS). Results indicated high rates of lifetime GBV among the sample
      (58%), as well as high rates of childhood sexual abuse (CSA) (22.2%). HIV
      infected women were more likely to be hopeless and to experience lower
      consideration of future consequences as compared to uninfected women.
      Multivariable analysis indicated that current non-injection drug use and a
      history of injection drug use were the main correlates of GBV and CSA, even when
      other psychosocial variables were included in analytic models. Being born outside
      of the US reduced the likelihood of GBV and CSA. Future research directions and
      intervention implications are discussed.

PMID- 24724989
TI  - Ammonia oxidation-dependent growth of group I.1b Thaumarchaeota in acidic red
      soil microcosms.
AB  - Accumulating evidence suggests that Thaumarchaeota may control nitrification in
      acidic soils. However, the composition of the thaumarchaeotal communities and
      their functioning is not well known. Therefore, we studied nitrification activity
      in relation to abundance and composition of Thaumarchaeota in an acidic red soil
      from China, using microcosms incubated with and without cellulose amendment.
      Cellulose was selected to simulate the input of crop residues used to increase
      soil fertility by local farming. Accumulation of NO3-(-N) was correlated with the
      growth of Thaumarchaeota as determined by qPCR of 16S rRNA and ammonia
      monooxygenase (amoA) genes. Both nitrification activity and thaumarchaeotal
      growth were inhibited by acetylene. They were also inhibited by cellulose
      amendment, possibly due to the depletion of ammonium by enhanced heterotrophic
      assimilation. These results indicated that growth of Thaumarchaeota was dependent
      on ammonia oxidation. The thaumarchaeotal 16S rRNA gene sequences in the red soil
      were dominated by a clade related to soil fosmid clone 29i4 within the group
      I.1b, which is widely distributed but so far uncultured. The archaeal amoA
      sequences were mainly related to the Nitrososphaera sister cluster. These
      observations suggest that fosmid clone 29i4 and Nitrososphaera sister cluster
      represent the same group of Thaumarchaeota and dominate ammonia oxidation in
      acidic red soil.

PMID- 24724990
TI  - Nanoimprinted comb structures in a low bandgap polymer: thermal processing and
      their application in hybrid solar cells.
AB  - In this paper, we investigate conjugated polymer layers structured by nanoimprint
      lithography toward their suitability for the fabrication of nanostructured
      polymer/metal sulfide hybrid solar cells. Consequently, we first study the
      thermal stability of the nanoimprinted conjugated polymer layers by means of
      scanning electron microscopy and grazing incidence small-angle X-ray scattering,
      which reveals a reasonable thermal stability up to 145  degrees C and sufficient
      robustness against the solvent mixture used in the subsequent fabrication
      process. In the second part, we demonstrate the preparation of nanostructured
      polymer/copper indium sulfide hybrid solar cells via the infiltration and thermal
      decomposition of a mixture of copper and indium xanthates. Although this step
      needs temperatures of more than 160  degrees C, the nanostructures are retained
      in the final polymer/copper indium sulfide layers. The nanostructured solar cells
      show significantly improved power conversion efficiencies compared to similarly
      prepared flat bilayer devices, which is based on a distinct improvement of the
      short circuit current in the nanostructured solar cells. 

PMID- 24724991
TI  - Studying rare genetic disorders in child neurology--the need for an international
      network of collaboration.

PMID- 24724992
TI  - Best practice when using the Strengths and Difficulties Questionnaire with
      extremely preterm children: are two informants better than one?

PMID- 24724993
TI  - Looking for predictors of functional outcomes in children with cerebellar
      abnormalities.

PMID- 24724994
TI  - Nutritional assessment: new tools and knowledge translation.

PMID- 24724995
TI  - Defining the indefinable? Capturing the ingredients of rehabilitation.

PMID- 24724996
TI  - A systematic review of the clinical relevance of repetitive transcranial magnetic
      stimulation.
AB  - OBJECTIVE: Repetitive transcranial magnetic stimulation (rTMS) is an approved
      treatment for depression. The clinical relevance of its efficacy is unclear. The
      clinical relevance of findings in the rTMS literature was assessed by translating
      Hamilton Depression Rating Scale (HAMD) data into Clinical Global Impression
      Improvement scale (CGI-I) scores. METHOD: We performed electronic searches of
      MEDLINE, Embase, PsycINFO, PubMed and Cochrane Central Register of Controlled
      Trials for RCTs and non-RCT trials on rTMS using Hamilton Depression Rating Scale
      (HAMD). Articles were included if published in English before January 2014. We
      translated HAMD scores into nominal CGI-I scores for rTMS for depression and for
      treatment-resistant depression (TRD). RESULTS: About 960 abstracts were
      retrieved. Sixty-three studies were included, yielding 130 study arms. For
      depression, the mean percentage change in HAMD scores in all sham-controlled rTMS
      treatment arms was 35.63 (SD 16.35) and for sham-rTMS 23.33 (SD 16.51). For TRD,
      active rTMS in sham-controlled studies showed a mean HAMD percentage reduction of
      45.21 (SD 10.94) versus 25.04 (SD 17.55) for sham-rTMS. When aggregated scores
      were translated into notional CGI-I scores, for the treatment of depression, the
      notional CGI-I score difference between rTMS and sham-rTMS was 0.5 in favour of
      rTMS; for TRD, it was 0.75 in favour of rTMS. Differences between rTMS and sham
      rTMS were bigger when all study arms were combined. CONCLUSION: Whilst rTMS
      appears to be efficacious for both non-refractory and treatment-resistant
      depression, the clinical relevance of its efficacy is doubtful.

PMID- 24725003
TI  - Mechanism of chitosan adsorption on silica from aqueous solutions.
AB  - We present a study of the adsorption of chitosan on silica. The adsorption
      behavior and the resulting layer properties are investigated by combining optical
      reflectometry and the quartz crystal microbalance. Exactly the same surfaces are
      used to measure the amount of adsorbed chitosan with both techniques, allowing
      the systematic combination of the respective experimental results. This
      experimental protocol makes it possible to accurately determine the thickness of
      the layers and their water content for chitosan adsorbed on silica from aqueous
      solutions of varying composition. In particular, we study the effect of pH in 10
      mM NaCl, and we focus on the influence of electrolyte type and concentration for
      two representative pH conditions. Adsorbed layers are stable, and their
      properties are directly dependent on the behavior of chitosan in solution. In
      mildly acidic solutions, chitosan behaves like a weakly charged polyelectrolyte,
      whereby electrostatic attraction is the main driving force for adsorption. Under
      these conditions, chitosan forms rigid and thin adsorption monolayers with an
      average thickness of approximately 0.5 nm and a water content of roughly 60%. In
      neutral solutions, on the other hand, chitosan forms large aggregates, and thus
      adsorption layers are significantly thicker (~10 nm) as well as dissipative,
      resulting in a large maximum of adsorbed mass around the pK of chitosan. These
      films are also characterized by a substantial amount of water, up to 95% of their
      total mass. Our results imply the possibility to produce adsorption layers with
      tailored properties simply by adjusting the solution chemistry during adsorption.

PMID- 24725006
TI  - Impact of molecular packing on electronic polarization in organic crystals: the
      case of pentacene vs TIPS-pentacene.
AB  - Polarization energy corresponds to the stabilization of the cation or anion state
      of an atom or molecule when going from the gas phase to the solid state. The
      decrease in ionization energy and increase in electron affinity in the solid
      state are related to the (electronic and nuclear) polarization of the surrounding
      atoms and molecules in the presence of a charged entity. Here, through a
      combination of molecular mechanics and quantum mechanics calculations, we
      evaluate the polarization energies in two prototypical organic semiconductors,
      pentacene and 6,13-bis(2-(tri-isopropylsilyl)ethynyl)pentacene (TIPS-pentacene).
      Comparison of the results for the two systems reveals the critical role played by
      the molecular packing configurations in the determination of the polarization
      energies and provides physical insight into the experimental data reported by
      Lichtenberger and co-workers (J. Amer. Chem. Soc. 2010, 132, 580; J. Phys. Chem.
      C 2010, 114, 13838). Our results underline that the impact of packing
      configurations, well established in the case of the charge-transport properties,
      also extends to the polarization properties of pi-conjugated materials. 

PMID- 24725005
TI  - Block and random copolymers bearing cholic acid and oligo(ethylene glycol)
      pendant groups: aggregation, thermosensitivity, and drug loading.
AB  - A series of block and random copolymers consisting of oligo(ethylene glycol) and
      cholic acid pendant groups were synthesized via ring-opening metathesis
      polymerization of their norbornene derivatives. These block and random copolymers
      were designed to have similar molecular weights and comonomer ratios; both types
      of copolymers showed thermosensitivity in aqueous solutions with similar cloud
      points. The copolymers self-assembled into micelles in water as shown by dynamic
      light scattering and transmission electron microscopy. The hydrodynamic diameter
      of the micelles formed by the block copolymer is much larger and exhibited a
      broad and gradual shrinkage from 20 to 54  degrees C below its cloud point, while
      the micelles formed by the random copolymers are smaller in size but exhibited
      some swelling in the same temperature range. Based on in vitro drug release
      studies, 78% and 24% paclitaxel (PTX) were released in 24 h from micelles self
      assembled by the block and random copolymers, respectively. PTX-loaded micelles
      formed by the block and random copolymers exhibited apparent antitumor efficacy
      toward the ovarian cancer cells with a particularly low half-maximal inhibitory
      concentration (IC50) of 27.4 and 40.2 ng/mL, respectively. Cholic acid-based
      micelles show promise as a versatile and potent platform for cancer chemotherapy.

PMID- 24725007
TI  - Meta-analysis of the effects of forest fragmentation on interspecific
      interactions.
AB  - Forest fragmentation dramatically alters species persistence and distribution and
      affects many ecological interactions among species. Recent studies suggest that
      mutualisms, such as pollination and seed dispersal, are more sensitive to the
      negative effects of forest fragmentation than antagonisms, such as predation or
      herbivory. We applied meta-analytical techniques to evaluate this hypothesis and
      quantified the relative contributions of different components of the
      fragmentation process (decreases in fragment size, edge effects, increased
      isolation, and habitat degradation) to the overall effect. The effects of
      fragmentation on mutualisms were primarily driven by habitat degradation, edge
      effects, and fragment isolation, and, as predicted, they were consistently more
      negative on mutualisms than on antagonisms. For the most studied interaction
      type, seed dispersal, only certain components of fragmentation had significant
      (edge effects) or marginally significant (fragment size) effects. Seed size
      modulated the effect of fragmentation: species with large seeds showed stronger
      negative impacts of fragmentation via reduced dispersal rates. Our results reveal
      that different components of the habitat fragmentation process have varying
      impacts on key mutualisms. We also conclude that antagonistic interactions have
      been understudied in fragmented landscapes, most of the research has concentrated
      on particular types of mutualistic interactions such as seed dispersal, and that
      available studies of interspecific interactions have a strong geographical bias
      (arising mostly from studies carried out in Brazil, Chile, and the United
      States).

PMID- 24725008
TI  - Encapsulation of a metal complex within a self-assembled nanocage: synergy
      effects, molecular structures, and density functional theory calculations.
AB  - A novel palladium-based metallacage was self-assembled. This nanocage displayed
      two complementary effects that operate in synergy for guest encapsulation.
      Indeed, a metal complex, [Pt(NO2)4](2-), was hosted inside the cavity, as
      demonstrated by solution NMR studies. Single-crystal X-ray diffraction shows that
      the guest adopts two different orientations, depending on the nature of the host
      guest interactions involved. A density functional theory computational study is
      included to rationalize this type of host-guest interaction. These studies pave
      the way to a better comprehension of chemical interaction and transformation
      within confined nanospaces. 

PMID- 24725009
TI  - Male mate choice relies on major histocompatibility complex class I in a sex-role
      reversed pipefish.
AB  - Mate choice for compatible genes is often based on genes of the major
      histocompatibility complex (MHC). Although MHC-based mate choice is commonly
      observed in female choice, male mate choice remains elusive. In particular, if
      males have intense paternal care and are thus the choosing sex, male choice for
      females with dissimilar MHC can be expected. Here, we investigated whether male
      mate choice relies on MHC class I genes in the sex-role reversed pipefish
      Syngnathus typhle. In a mate choice experiment, we determined the relative
      importance of visual and olfactory cues by manipulating visibility and olfaction.
      We found that pipefish males chose females that maximize sequence-based amino
      acid distance between MHC class I genotypes in the offspring when olfactory cues
      were present. Under visual cues, large females were chosen, but in the absence of
      visual cues, the choice pattern was reversed. The use of sex-role reversed
      species thus revealed that sexual selection can lead to the evolution of male
      mate choice for MHC class I genes. 

PMID- 24725010
TI  - Ultrafast microfluidic mixer for tracking the early folding kinetics of human
      telomere G-quadruplex.
AB  - The folding of G-quadruplex is hypothesized to undergo a complex process, from
      the formation of a hairpin structure to a triplex intermediate and to the final G
      quadruplex. Currently, no experimental evidence has been found for the hairpin
      formation, because it folds in the time regime of 10-100 MUs, entailing the
      development of microfluidic mixers with a mixing time of less than 10 MUs. In
      this paper, we reported an ultrarapid micromixer with a mixing time of 5.5 MUs,
      which represents the fastest turbulent micromixer to our best knowledge.
      Evaluations of the micromixer were conducted to confirm its mixing efficiency for
      small molecules and macromolecules. This new micromixer enabled us to interrogate
      the hairpin formation in the early folding process of human telomere G
      quadruplex. The experimental kinetic evidence for the formation of hairpin was
      obtained for the first time. 

PMID- 24725011
TI  - Determination of complete mitochondrial genome sequence from the holotype of the
      southern Mandarin dogfish Cirrhigaleus australis (Elasmobranchii: Squalidae).
AB  - We determined the complete mitochondrial genome sequence from the holotype of the
      southern Mandarin dogfish Cirrhigaleus australis. It has a length of 16,543 bp
      and consists of 13 protein-coding genes, 22 tRNA genes, 2 rRNA genes, and 1
      control region. The gene composition and genome organization is similar to most
      other vertebrates. Data obtained in this study will be important for resolving
      possible taxonomic issues related to C. australis and will contribute to the
      reconstruction of phylogenetic relationships among chondrichthyan species.

PMID- 24725012
TI  - Complete mitochondrial genome of milk sole fish Aseraggodes kobensis
      (Pleuronectiformes: Soleidae).
AB  - The complete mitochondrial genome of the milk sole fish Aseraggodes kobensis was
      determined in this study. It is 16,944 bp in length, contains 13 protein-coding
      genes, 22 tRNA genes, 2 rRNA genes and one putative control region with the
      typical gene order and transcriptional orientation in vertebrates. The nucleotide
      base content of A. kobensis mitochondrial genome is: 31.7% A, 27.3% C, 15.3% G
      and 25.8% T. There are 24 bp overlaps and 48 bp short intergenic spaces located
      in 6 and 12 gene junctions, respectively. Two start codons (ATG and GTG) and two
      stop codons (TAG and TAA/T) were found in protein-coding genes. The origin of L
      strand replication sequence was found between the tRNA(Asn) and tRNA(Cys) genes,
      and could be folded into a hairpin structure. The control region is 1239 bp in
      length with the rich A+T (66.4%) and poor G (13.1%) content.

PMID- 24725013
TI  - The complete mitochondrial genome of the Babylonia areolata.
AB  - The complete mitochondrial genome sequence of the Babylonia areolata was
      determined using PCR-based method. The total length of the mitogenome is 15,356
      bp, including 2 ribosomal RNA genes, 13 protein-coding genes, 22 transfer RNA
      genes. The overall composition of the mitogenome was estimated to be 29.31% for
      A, 37.41% for T, 16.59% for C, and 16.70% for G, respectively, indicating that an
      A + T (66.72%)-rich feature occurs in the Babylonia areolata mitogenome.

PMID- 24725014
TI  - The complete mitochondrial genome of the Yorkshire pig (Sus scrofa).
AB  - This study aims to identify the complete nucleotide sequence of mitochondrial
      genome in the Yorkshire pig. Sequence analysis indicates that the genome
      structure is in accordance with other pig breeds, and it contains 22 tRNA genes,
      2 ribosomal RNA genes, 13 protein-coding genes and 1 control region (D-loop
      region). The complete mitochondrial genome sequence of the Yorkshire pig provides
      an important record set for further study on genetic mechanism. 

PMID- 24725015
TI  - The complete mitochondrial genome of Pseudobagrus emarginatus (Siluriformes:
      Bagridae).
AB  - In this study, the total mitochondrial genome sequence of Pseudobagrus
      emarginatus (Siluriformes: Bagridae) was firstly sequenced and determined. The
      complete mtDNA genome sequence of P. emarginatus is 16,534 bp in length. It
      consists of 22 transfer RNA genes, 2 ribosomal RNA genes, 13 protein-coding
      genes, and a non-coding control region (D-loop). The overall-based composition
      was 31.5% A, 26.8% T, 14.9% G and 26.8% C, with a high A+T content (58.3%), which
      was nearly the same as other reported catfishes. These results will provide
      useful data to the natural resources conservation and systematics analysis of P.
      emarginatus and its related species in future.

PMID- 24725016
TI  - Probing the inner space of salt-bridged calix[5]arene capsules.
AB  - A combined DOSY and XRD study indicates that a carboxylcalix[5]arene receptor is
      able to encapsulate alpha,omega-diamines of appropriate length by means of a
      proton-transfer-mediated recognition process followed by salt-bridge-assisted bis
      endo-complexation. 

PMID- 24725017
TI  - CT scan does not predict optimal debulking in stage III-IV epithelial ovarian
      cancer: a multicentre validation study.
AB  - Our aim was to design and validate a model of CT findings that predict suboptimal
      cytoreduction in primary surgery (PS) for Stage III-IV epithelial ovarian cancer
      (EOC). We performed a retrospective review of preoperative CT scans of patients
      undergoing PS for EOC in a cancer centre in London, UK, between November 1995 and
      October 2003 (n = 91). Radiological features predictive of suboptimal
      cytoreduction were identified and the model tested in a second cohort undergoing
      PS in Manchester, June 2005 - March 2007 (n = 35). In the London cohort, liver
      surface disease and infrarenal para-aortic lymph node involvement predicted
      suboptimal cytoreduction with 80% accuracy. Accuracy of these predictors dropped
      to 63% when applied to the Manchester cohort. We concluded that CT prediction of
      suboptimal cytoreduction is unreliable and may not be reproducible. In the
      absence of favourable data from larger, prospective trials, it should not be used
      to guide management.

PMID- 24725018
TI  - Gene delivery for cancer therapy.
AB  - Gene therapy has potential in the treatment of human cancers. However, its
      clinical implication has only achieved little success due to the lack of an
      efficient gene delivery system. A major hurdle in the current available
      approaches is in the ability to transduce target tissues at very high
      efficiencies that ultimately lead to therapeutic levels of transgene expression.
      This review outlines the characteristics and utilities of several available gene
      delivery systems, including their advantages and drawbacks in the context of
      cancer treatment. A perspective of existing challenges and future directions is
      also included. 

PMID- 24725019
TI  - Central pontine myelinolysis following pediatric living donor liver
      transplantation: a case report and review of literature.
AB  - CPM is one of the most serious neurological complications that can occur after
      OLT and is characterized by symmetrical demyelinization in the basis pontis. The
      etiology of CPM remains unclear, although the rapid correction of the serum
      sodium and CNI concentrations may be associated with the development of CPM. With
      recent advances in MRI technology, early diagnosis of CPM has become possible.
      Here, we present the case of a five-yr-old female who developed CNI-associated
      CPM after undergoing LDLT. A decreased level of consciousness and dysphasia was
      noted one wk after LDLT, and MRI revealed findings compatible with a diagnosis of
      CPM. The patient fully recovered from the neurological deficits related to CPM
      following the switch from the CNI to sirolimus. We propose MRI to be promptly
      considered for patients with abnormal neurological findings, together with the
      substitution of CNI with an mTOR inhibitor as a management regimen for CNI
      related CPM. 

PMID- 24725020
TI  - Defining the genomic landscape of head and neck cancers through next-generation
      sequencing.
AB  - Next-generation sequencing (NGS) has revolutionized the field of genomics and
      improved our understanding of cancer biology. Advances have been achieved by
      sequencing tumor DNA and using matched normal DNA to filter out germ line
      variants to identify cancer-specific changes. The identification of high
      incidences of activating mutations in head and neck squamous cell carcinoma
      (HNSCC) amenable to drug targeting has been made, with clear distinctions between
      the mutational profile of HPV-positive and HPV-negative tumors. This wealth of
      new understanding undoubtedly ameliorates our understanding of HNSCC cancer
      biology and elucidates clear targets for drug targeting which will guide future
      personalized medicine. 

PMID- 24725021
TI  - Optically modulated fluorescence bioimaging: visualizing obscured fluorophores in
      high background.
AB  - Fluorescence microscopy and detection have become indispensible for understanding
      organization and dynamics in biological systems. Novel fluorophores with improved
      brightness, photostability, and biocompatibility continue to fuel further
      advances but often rely on having minimal background. The visualization of
      interactions in very high biological background, especially for proteins or bound
      complexes at very low copy numbers, remains a primary challenge. Instead of
      focusing on molecular brightness of fluorophores, we have adapted the principles
      of high-sensitivity absorption spectroscopy to improve the sensitivity and signal
      discrimination in fluorescence bioimaging. Utilizing very long wavelength
      transient absorptions of kinetically trapped dark states, we employ molecular
      modulation schemes that do not simultaneously modulate the background
      fluorescence. This improves the sensitivity and ease of implementation over high
      energy photoswitch-based recovery schemes, as no internal dye reference or
      nanoparticle-based fluorophores are needed to separate the desired signals from
      background. In this Account, we describe the selection process for and
      identification of fluorophores that enable optically modulated fluorescence to
      decrease obscuring background. Differing from thermally stable photoswitches
      using higher-energy secondary lasers, coillumination at very low energies
      depopulates transient dark states, dynamically altering the fluorescence and
      giving characteristic modulation time scales for each modulatable emitter. This
      process is termed synchronously amplified fluorescence image recovery (SAFIRe)
      microscopy. By understanding and optically controlling the dye photophysics, we
      selectively modulate desired fluorophore signals independent of all
      autofluorescent background. This shifts the fluorescence of interest to unique
      detection frequencies with nearly shot-noise-limited detection, as no background
      signals are collected. Although the fluorescence brightness is improved slightly,
      SAFIRe yields up to 100-fold improved signal visibility by essentially removing
      obscuring, unmodulated background (Richards, C. I.; J. Am. Chem. Soc. 2009, 131,
      4619). While SAFIRe exhibits a wide, linear dynamic range, we have demonstrated
      single-molecule signal recovery buried within 200 nM obscuring dye. In addition
      to enabling signal recovery through background reduction, each dye exhibits a
      characteristic modulation frequency indicative of its photophysical dynamics.
      Thus, these characteristic time scales offer opportunities not only to expand the
      dimensionality of fluorescence imaging by using dark-state lifetimes but also to
      distinguish the dynamics of subpopulations on the basis of photophysical versus
      diffusional time scales, even within modulatable populations. The continued
      development of modulation for signal recovery and observation of biological
      dynamics holds great promise for studying a range of transient biological
      phenomena in natural environments. Through the development of a wide range of
      fluorescent proteins, organic dyes, and inorganic emitters that exhibit
      significant dark-state populations under steady-state illumination, we can
      drastically expand the applicability of fluorescence imaging to probe lower
      abundance complexes and their dynamics.

PMID- 24725022
TI  - Attention-deficit hyperactivity disorder (ADHD): an updated review of the
      essential facts.
AB  - Attention-deficit hyperactivity disorder (ADHD) is a complex disorder that can
      affect individuals across the lifespan. It is associated with substantial
      heterogeneity in terms of aetiology, clinical presentation and treatment outcome
      and is the subject of extensive research. Because of this, it can be difficult
      for clinicians to stay up to date with the most relevant findings and know how
      best to respond to parents' questions and concerns about the disorder and
      interventions. This is a narrative review that aims to summarize key findings
      from recent research into ADHD and its treatment that clinicians can share with
      families in order to increase their knowledge about ADHD and intervention
      options. ADHD develops as a result of complex interplay between interdependent
      genetic and non-genetic factors. The disorder is associated with substantial
      impairments in functioning and poor long-term outcomes. Pharmacological and non
      pharmacological treatment options are available for symptom management and to
      improve function, but functioning outcomes often fail to normalize in children
      with ADHD. Despite extensive advances in understanding this complex disorder, it
      is clear that there is still a long way to go. In particular, we address the need
      for future non-pharmacological interventions to be more specifically targeted for
      ADHD symptoms and its commonly associated functioning deficits in order to ensure
      the best long-term outcomes for children with ADHD. 

PMID- 24725023
TI  - Septic transfusion reactions during blood transfusion via indwelling central
      venous catheters.
AB  - BACKGROUND: Transfusion of blood products requires a vascular port. Use of an
      indwelling central venous catheter (CVC) provides this port readily and safely in
      general; however, potential risks require assessment. STUDY DESIGN AND METHODS:
      The objective was to examine septic reactions to blood transfusions performed via
      CVCs owing to subclinical microbial catheter colonization. All transfusion
      reactions that occurred from 2007 to 2011 at The University of Texas MD Anderson
      Cancer Center were analyzed and correlated with microbiology culture results.
      Data on the reactions, including vascular access via a catheter or peripheral
      venipuncture, were collected prospectively. RESULTS: A total of 999 reactions
      were reported, with an incidence of two per 1000 transfusion events. A total of
      738 reactions occurred in 642 patients during transfusion through a CVC. Among
      them, 606 reactions occurred in patients that had cultures of blood samples drawn
      within 7 days before or after reaction. Sixty of these (9.9%) had at least one
      significant microorganism isolated from their catheters and/or peripheral blood.
      The blood culture results and timing suggested that these patients likely had
      catheter-related bloodstream infections caused by transfusion through a CVC with
      subclinical microbial colonization. Fever and chills occurred in 35 of these
      patients (58%), which resembled febrile nonhemolytic transfusion reactions.
      Culture results of the transfused blood products, although not performed in all
      cases, were mostly negative in these CVC-related reactions. CONCLUSION: Blood
      transfusion through an indwelling CVC may lead to septic reaction owing to
      subclinical microbial colonization. This risk should be considered before
      transfusion and during investigation of transfusion reactions.

PMID- 24725024
TI  - A controlled trial of intravenous immunoglobulin in multifocal motor neuropathy.
AB  - Intravenous immunoglobulin (IVIG) has become the standard treatment for
      multifocal motor neuropathy (MMN) based on limited data. To critically assess the
      efficacy, safety, and tolerability of 10% liquid IVIG (IVIG), 44 adults with MMN
      were randomized 1 : 1 to either double-blind treatment of IVIG followed by
      placebo for 12 weeks each or the reverse. Open-label IVIG was administered for 12
      weeks at the beginning and end of the study for clinical stabilization, and
      between double-blinded periods to prevent a carry-over effect. To avoid potential
      worsening, switching to open-label IVIG was permitted if deterioration occurred
      during blinded treatment. Mean maximal grip strength of the more affected hand
      declined 31.38% during placebo and increased 3.75% during IVIG (p = 0.005). In
      35.7% of participants, Guy's Neurological Disability scores for upper limbs
      worsened during placebo and not during IVIG, whereas the converse was true in
      11.9% (p = 0.021). Sixty-nine percent (69.0%) switched prematurely from placebo
      to open-label IVIG and 2.4% switched from blinded to open-label IVIG (p < 0.001).
      One serious adverse reaction (pulmonary embolism) and 100 non-serious reactions
      (69 mild, 20 moderate, and 11 severe) to IVIG occurred. IVIG was effective in
      improving disability and muscle strength, and was safe and well tolerated in
      adults with MMN. 

PMID- 24725025
TI  - Similar therapeutic efficacy between a single administration of gene therapy and
      multiple administrations of recombinant enzyme in a mouse model of lysosomal
      storage disease.
AB  - Enzyme replacement therapy (ERT) has become the standard of care for several
      lysosomal storage disorders (LSDs). Despite ERT's undisputed efficacy, the
      requirement for multiple and costly administrations as well as ERT's limited
      improvement of some LSD manifestations prompts the search for better therapies.
      Using a mouse model of mucopolysaccharidosis VI, we compared the efficacy of a
      single intravascular administration of an adeno-associated viral vector targeting
      liver to weekly infusions of human recombinant enzyme at the same doses used in
      mucopolysaccharidosis VI patients. While gene therapy results in increased and
      stable levels of circulating enzyme up to 1 year after vector administration, ERT
      has typical peak-and-drop serum kinetics. Both therapies similarly reduced
      glycosaminoglycan levels in urine and tissues including heart valves and
      myocardium, with gene therapy improving skeletal skull abnormalities slightly
      better, although not significantly, than ERT. Both therapies seem to similarly
      improve animal motor performance, with gene therapy possibly associated with less
      animal distress. Thus, a single vector administration that converts liver into a
      factory organ for systemic secretion of therapeutic proteins is at least as
      effective as ERT in a mouse model of LSD, potentially eliminating problems with
      compliance and costs. Only testing in humans will prove whether this holds true
      in a clinical setting.

PMID- 24725026
TI  - Formulation, development and optimization of raloxifene-loaded chitosan
      nanoparticles for treatment of osteoporosis.
AB  - CONTEXT: Osteoporosis (OP) is a disease of skeletal system and is associated with
      fragility fracture at the hip, spine and wrist. Various drugs have been used to
      treat OP. One of them is raloxifene hydrochloride (RLX), a second-generation
      selective estrogen receptor modulator (SERM) approved by the USFDA. RLX possesses
      only 2% absolute bioavailability (BA) by oral route due to its extensive first
      pass metabolism. OBJECTIVE: The purpose of the current research work was to
      develop and evaluate RLX-loaded chitosan nanoparticles (CS-NPs) for treatment of
      OP with enhanced BA. MATERIALS AND METHODS: The RLX-loaded CS-NPs were prepared
      by gelation of CS with tripolyphosphate (TPP) by ionic cross-linking. Formulation
      was optimized and in vitro drug release and in vivo study were performed. RESULTS
      AND DISCUSSIONS: CS-NPs were formed by the ionic gelation method. The particle
      size, entrapment efficiency and loading efficiency varied from 216.65 to 1890 nm,
      32.84 to 97.78% and 23.89 to 62.46%, respectively. Release kinetics showed
      diffusion-controlled and Fickian release pattern. In vivo study indicated higher
      plasma drug concentration with NPs administered intranasally as compared to drug
      suspension administered through oral route (p < 0.05). A significantly higher
      drug concentration in plasma was achieved in 10 min after nasal administration
      with respect to oral administration. CONCLUSION: The results suggest that RLX
      loaded CS-NPs have better BA and would be a promising approach for intranasal
      (i.n.) delivery of RLX for the treatment of OP.

PMID- 24725027
TI  - Microbeads mediated oral plasmid DNA delivery using polymethacrylate vectors: an
      effectual groundwork for colorectal cancer.
AB  - This study was aimed to develop and evaluate p53 polyplex-loaded enteric-coated
      calcium pectinate microbeads for oral gene delivery as an effective novel
      alternative for colorectal cancer therapy. Mutation in p53 is the key event in
      colorectal cancer (CRC) and an important target for the treatment of CRC through
      gene therapy. Polymethacrylates-based non-viral vectors were evaluated for their
      ability to complex, protect and transfect p53 (wt) into colon cancer cell line.
      Polyplexes were formulated by complexation of cationic polymer with anionic pDNA
      at different N/P ratios. p53 polyplex-loaded calcium pectinate (CP) microbeads
      were prepared by ionotropic gelation of pectin with calcium chloride and coated
      with Eudragit(r) S100. In vitro release studies showed that enteric-coated CP
      microbeads protected the release of p53 polyplex in upper GIT with less than 10%
      release. In-vitro cell line studies and in vivo studies in rat showed that
      polymethacrylate carrier could transfect the pDNA effectively. Results of in vivo
      gene expression study further confirmed the ability of enteric-coated calcium
      pectinate microbeads to deliver pDNA specifically to rat colon. Conclusively,
      enteric-coated calcium pectinate microbeads released p53 polyplex specifically in
      colon and could serve as an effective alternative for CRC therapy. 

PMID- 24725028
TI  - Linear-dendrimer type methoxy-poly (ethylene glycol)-b-poly (epsilon
      caprolactone) copolymer micelles for the delivery of curcumin.
AB  - PURPOSE: To improve curcumin's pharmacokinetic, in vitro cytotoxicity and release
      property. METHODS: A novel linear-dendrimer methoxy-poly (ethylene glycol)-b-poly
      (epsilon-caprolactone) copolymer was synthesized through O-alkylation, basic
      hydrolysis and ring-opening polymerization reaction with methoxy-poly (ethylene
      glycol), epichlorohydrin and epsilon-caprolactone as raw materials. Its structure
      was characterized by (1)H-NMR and GPC. The copolymer's hemolysis and micellar
      encapsulation for curcumin by thin-film hydration were studied. Curcumin-loaded
      micelles were evaluated by use of in vitro release, FT-IR and X-ray diffraction.
      Curcumin-loaded micelles' in vitro cytotoxic activities against Hela and HT-29
      cells were done, and its pharmacokinetic parameters were also carried out.
      RESULTS: Curcumin was encapsulated into the micelles with 92.54% of entrapment
      efficiency and 12.84% of drug loading in amorphous forms. The dissolubility of
      nanoparticulate curcumin was 1.70 * 10(5) times higher than that of curcumin in
      water. The obtained copolymer showed no hemolysis. In vitro drug release study
      indicated that, in all cases, the kinetics was adjusted well to the Makoid
      Banakar model ([Formula: see text] = 0.9984). In addition, data were analyzed by
      the Korsmeyer-Peppas model, n values were 0.43, indicating that the drug release
      was accomplished by the combination diffusion and polymer chain relaxation. The
      cytotoxicity experiment indicated that the nanoparticulate curcumin kept up its
      potent anti-cancer activities. The pharmacokinetic results showed that the MRT0
      infinity, t1/2z and AUC0-infinity of Curcumin-loaded micelles were 1.64, 6.54 and
      4.67 times higher than that of CUR control solution. CONCLUSIONS: The copolymeric
      micelles loading curcumin might act as a delivery vehicle for CUR.

PMID- 24725029
TI  - Transdermal microemulsions of Boswellia carterii Bird: formulation,
      characterization and in vivo evaluation of anti-inflammatory activity.
AB  - CONTEXT: Boswellia species are trees (family: Bruseraceae) found in India,
      Northern Africa and the Middle East. OBJECTIVE: This study aims at formulating
      low dose biologically active fraction from the oleogum resin of Boswellia
      carterii (BC) in transdermal (TD) microemulsions (MEs) to acquire promoted anti
      inflammatory efficacy. MATERIALS AND METHODS: The bioactive fraction of the
      oleogum resin of BC was tested for solubility in different components. The most
      efficient were selected for constructing phase diagrams for ME preparation. The
      bioactive fraction was assayed by high performance liquid chromatography for 3
      acetyl-11-keto-beta-boswellic acid (AKBA), at 210 nm. The bioactive fraction was
      incorporated in 6 MEs. ME systems were evaluated for drug content and optimized
      systems were tested for characterization, permeation, skin irritancy and in vivo
      evaluation of anti-inflammatory activity. RESULTS AND DISCUSSION: Two systems
      were selected; ME1 and ME4 composed of Tween 80: PEG 400 at 1:1 and 2:1 ratio,
      with oil content 7.78 and 17.5%, respectively. The systems showed high
      encapsulation efficiency >83%, small droplet size <100 nm, and suitable pH for
      topical application. Permeation parameters for ME1 were higher compared to ME4.
      Both MEs were non irritant. ME1 showed significantly higher anti-inflammatory
      activity versus the standard TD anti-inflammatory piroxicam. CONCLUSIONS:
      Optimized TD BC MEs could be used as a safe, effective and long acting
      alternative to oral anti-inflammatories, providing higher and prolonged efficacy
      and better patient compliance.

PMID- 24725030
TI  - Human leukocyte antigen matching in heart transplantation: systematic review and
      meta-analysis.
AB  - Allocation of donors with regard to human leukocyte antigen (HLA) is
      controversial in heart transplantation. This paper is a systematic review and
      meta-analysis of the available evidence. PubMed, Embase, and the Cochrane Library
      were searched systematically for studies that addressed the effects of HLA
      matching on outcome after heart transplantation. Fifty-seven studies met the
      eligibility criteria. 34 studies had graft rejection as outcome, with 26 of the
      studies reporting a significant reduction in graft rejection with increasing
      degree of HLA matching. Thirteen of 18 articles that reported on graft failure
      found that it decreased significantly with increasing HLA match. Two multicenter
      studies and nine single-center studies provided sufficient data to provide
      summary estimates at 12 months. Pooled comparisons showed that graft survival
      increased with fewer HLA-DR mismatches [0-1 vs. 2 mismatches: risk ratio (RR) =
      1.09 (95% confidence interval (CI): 1.01-1.19; P = 0.04)]. Having fewer HLA-DR
      mismatches (0-1 vs. 2) reduced the incidence of acute rejection [(RR = 0.81 (0.66
      0.99; P = 0.04)]. Despite the considerable heterogeneity between studies, the
      short observation time, and older data, HLA matching improves graft survival in
      heart transplantation. Prospective HLA-DR matching is clinically feasible and
      should be considered as a major selection criterion. 

PMID- 24725031
TI  - Association of footprint measurements with plantar kinetics: a linear regression
      model.
AB  - BACKGROUND: The use of foot measurements to classify morphology and interpret
      foot function remains one of the focal concepts of lower-extremity biomechanics.
      However, only 27% to 55% of midfoot variance in foot pressures has been
      determined in the most comprehensive models. We investigated whether dynamic
      walking footprint measurements are associated with inter-individual foot loading
      variability. METHODS: Thirty individuals (15 men and 15 women; mean +/- SD age,
      27.17 +/- 2.21 years) walked at a self-selected speed over an electronic
      pedography platform using the midgait technique. Kinetic variables (contact time,
      peak pressure, pressure-time integral, and force-time integral) were collected
      for six masked regions. Footprints were digitized for area and linear boundaries
      using digital photo planimetry software. Six footprint measurements were
      determined: contact area, footprint index, arch index, truncated arch index,
      Chippaux-Smirak index, and Staheli index. Linear regression analysis with a
      Bonferroni adjustment was performed to determine the association between the
      footprint measurements and each of the kinetic variables. RESULTS: The findings
      demonstrate that a relationship exists between increased midfoot contact and
      increased kinetic values in respective locations. Many of these variables
      produced large effect sizes while describing 38% to 71% of the common variance of
      select plantar kinetic variables in the medial midfoot region. In addition,
      larger footprints were associated with larger kinetic values at the medial heel
      region and both masked forefoot regions. CONCLUSIONS: Dynamic footprint
      measurements are associated with dynamic plantar loading kinetics, with emphasis
      on the midfoot region.

PMID- 24725032
TI  - An initial evaluation of a proof-of-concept 128-Hz electronic tuning fork in the
      detection of peripheral neuropathy.
AB  - BACKGROUND: Diabetic peripheral neuropathy (DPN) is an essential precursor
      leading to diabetic limb loss. Neurologic screening tests, including the 128-Hz
      tuning fork (TF), have long been used to identify and track the progression of
      DPN, thereby guiding the implementation of preventive strategies. Although a
      sensitive indicator of neuropathy, shortcomings of TF testing include the lack of
      standardization and quantification of clinical findings. In an attempt to
      overcome these limitations, a novel 128-Hz electronic TF (ETF) prototype has been
      developed that is capable of performing accurate timed vibration tests (TVTs).
      This study was designed to assess the ability of the ETF to detect sensory
      impairment compared with three established neurologic screening methods: the
      Semmes-Weinstein monofilament test, the biothesiometer, and the sharp/dull
      discrimination test. METHODS: Fifty-five test patients were recruited from the
      primary author's practice and enrolled according to an approved protocol. The 10
      g Semmes-Weinstein monofilament test and the sharp/dull discrimination test were
      administered in standard fashion to the plantar aspects of digits 1 and 5
      bilaterally. The ETF and the biothesiometer (25-V setting) were applied to the
      dorsal aspects of the distal phalanx of the hallux and fifth metatarsal head
      bilaterally. RESULTS: The sensitivity and specificity of neuropathy detection for
      the ETF were 0.953 and 0.761, respectively, using conventional tests as reference
      standards. CONCLUSIONS: Performance of TVTs with the ETF detected sensory
      impairment compared with three conventional neurologic screening methods. Given
      these findings, the ETF could facilitate the use of standardized TVTs as an
      indicator of DPN progression.

PMID- 24725033
TI  - Human papillomavirus types 2, 27, and 57 Identified in plantar verrucae from HIV
      positive and HIV-negative individuals.
AB  - BACKGROUND: Although an increased prevalence of plantar verrucae has been
      associated with human immunodeficiency virus (HIV) infection, human
      papillomavirus (HPV) typing studies have not been published about this patient
      population. We sought to determine the prevalence of HPV types in plantar
      verrucae of HIV-positive (HIV+) and HIV-negative (HIV-) individuals. METHODS:
      Thirty-nine plantar verruca lesions in 17 individuals were examined. Nine
      participants were HIV+ and eight were HIV-. Detection of HPV was performed by
      polymerase chain reaction using two sets of primers: MY09/MY11. The type of HPV
      was determined by hybridization to 38 different HPV types. Clinical types of
      verrucae were correlated to the HPV strain identified in each lesion. RESULTS: Of
      the 39 plantar verruca samples, 38 typed to HPV-2, HPV-27, and HPV-57 strains in
      HIV+ and HIV- individuals. Specifically, a large proportion of the samples from
      HIV- individuals typed as HPV-27 (87.5%), and HPV-2 was the predominant type
      identified in HIV+ individuals (50%). No rare or atypical HPV types were found in
      either group. We identified HPV-2 and HPV-27 in 96% of verruca plantaris clinical
      type. Mosaic warts typed to HPV-27 and HPV-57, and 80% of punctate verrucae typed
      to HPV-57. CONCLUSIONS: This study presents an increased prevalence of HPV-2, HPV
      27, and HPV-57 in plantar verrucae in this study population and provides insight
      into the occurrence of these types in HIV+ and HIV- individuals.

PMID- 24725034
TI  - Evaluation of wound care and health-care use costs in patients with diabetic foot
      ulcers treated with negative pressure wound therapy versus advanced moist wound
      therapy.
AB  - BACKGROUND: We conducted a post-hoc retrospective analysis of patients enrolled
      in a randomized controlled trial to evaluate overall costs of negative pressure
      wound therapy (NPWT; V.A.C. Therapy; KCI USA, Inc, San Antonio, Texas) versus
      advanced moist wound therapy (AMWT) in treating grade 2 and 3 diabetic foot
      wounds during a 12-week therapy course. METHODS: Data from two study arms (NPWT
      [n = 169] or AMWT [n = 166]) originating from Protocol VAC2001-08 were collected
      from patient records and used as the basis of the calculations performed in our
      cost analysis. RESULTS: A total of 324 patient records (NPWT = 162; AMWT = 162)
      were analyzed. There was a median wound area reduction of 85.0% from baseline in
      patients treated with NPWT compared to a 61.8% reduction in those treated with
      AMWT. The total cost for all patients, regardless of closure, was $1,941,472.07
      in the NPWT group compared to $2,196,315.86 in the AMWT group. In patients who
      achieved complete wound closure, the mean cost per patient in the NPWT group was
      $10,172 compared to $9,505 in the AMWT group; the median cost per 1 cm(2) of
      closure was $1,227 with NPWT and $1,695 with AMWT. In patients who did not
      achieve complete wound closure, the mean total wound care cost per patient in the
      NPWT group was $13,262, compared to $15,069 in the AMWT group. The median cost to
      close 1 cm(2) in wounds that didn't heal using NPWT was $1,633, compared to
      $2,927 with AMWT. CONCLUSIONS: Our results show greater cost effectiveness with
      NPWT versus AMWT in recalcitrant wounds that didn't close during a 12-week
      period, due to lower expenditures on procedures and use of health-care resources.

PMID- 24725035
TI  - The foot posture index in men practicing three sports different in their
      biomechanical gestures.
AB  - BACKGROUND: The technical gestures characteristic of certain sports may lead to
      one type of foot being more prevalent than the others. The Foot Posture Index
      (FPI) has been used as a diagnostic tool for support postures in various sports,
      but the differences in these postures between sports of distinct gestures in
      their actions are far from completely understood. METHODS: The overall FPI,
      obtained as the sum of the scores of its six individual criteria, was determined
      in 90 male athletes (30 runners, 30 basketball players, and 30 handball players)
      in static bipedal stance and relaxed position. Analysis of variance was used to
      find significant differences among the three sports in the total FPI and its six
      criteria. RESULTS: The mean +/- SD FPI was 2.9 +/- 2.8 in runners, 3.9 +/- 4.1 in
      basketball players, and -0.4 +/- 6.9 in handball players, with significant
      differences among these groups (P = .008). Significant differences were also
      found in the talar head position and talonavicular prominence values between
      handball players and runners (P = .001 and P = .004, respectively) and between
      handball and basketball players (P = .002 and P = .006, respectively).
      CONCLUSIONS: Runners and basketball players had neutral feet, whereas handball
      players had supinated feet. The differences in foot posture seem to be mainly
      determined by two of the FPI criteria: talar head position and talonavicular
      prominence.

PMID- 24725036
TI  - Daptomycin for methicillin-resistant Staphylococcus aureus diabetic foot
      infections.
AB  - BACKGROUND: Diabetic foot infection (DFI) is a serious, difficult-to-treat
      infection, especially when caused by methicillin-resistant Staphylococcus aureus
      (MRSA). Vancomycin has been the standard treatment for MRSA infection, but lower
      response rates in MRSA skin infections have been reported. This analysis assessed
      the outcome and safety of daptomycin therapy in patients with a DFI caused by
      MRSA. METHODS: Using the Cubicin Outcomes Registry and Experience and the
      European Cubicin Outcomes Registry and Experience (2006-2009), 79 patients with
      MRSA DFI were identified and included in this analysis. RESULTS: In the 74
      evaluable patients, daptomycin was administered at a median dose of 4.8 mg/kg
      primarily every 24 hours (85.1%) and for a median of 15.0 days. Overall, 77.0% of
      the patients (57 of 74) received initial therapy with activity against MRSA;
      however, of patients receiving daptomycin as second-line therapy (n = 31), only
      45.2% were treated with an antibiotic agent active against MRSA. The overall
      clinical success and treatment failure rates were 89.2% and 10.8%, respectively.
      Success with daptomycin therapy was higher in patients who had surgery and in
      those whose initial therapy was daptomycin. Eleven patients had 14 adverse
      events, two of which were possibly related to daptomycin use and led to
      discontinuation. CONCLUSIONS: In a large real-world cohort of patients with MRSA
      DFI, daptomycin therapy was shown to be generally well tolerated and effective.
      The use of an anti-MRSA antibiotic agent should be considered when implementing
      first-line antibiotic drug therapy for DFI in countries where MRSA is common to
      avoid inappropriate empirical treatment and potential negative effects on
      outcomes.

PMID- 24725037
TI  - Hallux abductus interphalangeus in normal feet, early-stage hallux limitus, and
      hallux valgus.
AB  - BACKGROUND: Excessive deviation of the distal phalanx in abduction frequently
      occurs in advanced stages of hallux rigidus but not in hallux valgus. Therefore,
      theoretically there should be no significant differences in the hallux
      interphalangeal angle (HIPA) between individuals with normal feet, those with
      hallux valgus, and those with mild hallux limitus. The objective of the present
      study was thus to determine if significant differences in HIPA exist in the early
      stages of hallux valgus or hallux limitus deformities. METHODS: The hallux
      interphalangeal angle was measured in three groups of participants: a control
      group with normal feet (45 participants), a hallux valgus group (49
      participants), and a hallux limitus group (48 participants). Both of the
      pathologies were at an early stage. A dorsoplantar radiograph under weightbearing
      conditions was taken for each individual, and measurements (HIPA and hallux
      abductus angle [HAA]) were taken using AutoCAD (Autodesk Inc, San Rafael,
      California) software. Intergroup comparisons of HIPA, and correlations between
      HIPA, HAA, and hallux dorsiflexion were calculated. RESULTS: The comparisons
      revealed no significant differences in the values of HIPA between any of the
      groups (15.2 +/- 5.9 degrees in the control group, 15.5 +/- 3.9 degrees in the
      hallux valgus group, and 16.15 +/- 4.3 in the hallux limitus group; P  =  0.634).
      The Pearson correlation coefficients in particular showed no correlation between
      hallux dorsiflexion, HAA, and HIPA. CONCLUSIONS: For the study participants,
      there were similar deviations of the distal phalanx of the hallux with respect to
      the proximal phalanx in normal feet and in feet with the early stages of the
      hallux limitus and hallux valgus deformities.

PMID- 24725038
TI  - Do educational interventions targeted to nail salon workers and customers improve
      infection control practices in these salons?
AB  - BACKGROUND: The Tacoma-Pierce County Department of Health, the Pierce County
      Antibiotic Resistance Task Force, and the Washington State Department of
      Licensing (DOL) designed an intervention to determine whether nail salon
      infection control practices could be improved by educating salon employees and
      their customers about good infection control practices. METHODS: Twenty
      intervention salons and 26 control salons completed the 3-month study. The
      intervention group received a letter asking them to "join our campaign to promote
      healthy people in healthy communities ... ." Two DOL pamphlets on cleaning and
      disinfecting and a tent card with important infection control reminders-targeted
      to clients on one side and to salon workers on the other side-were also included.
      Outreach workers from the health department visited 25 (of the original 27)
      intervention salons once and talked about the materials included in the mailing.
      Inspection infractions were used to measure compliance with infection control
      practices. Each salon was inspected by the DOL at baseline, within 1 month after
      the educational mailing, and within 1 month after an outreach visit from the
      local health department. RESULTS: Both groups exhibited statistically significant
      decreases in infractions; however, the intervention group exhibited a higher and
      more significant decrease in infractions than the control group. CONCLUSIONS: The
      intervention and control groups underwent three DOL inspections, which may have
      resulted in a Hawthorne Effect, with both groups seeing a statistically
      significant decline in infractions after inspection visits. The more significant
      decrease in the number of infractions cited in the intervention salons may be due
      to the educational materials and the health education site visit they received.

PMID- 24725039
TI  - Pitted keratolysis: a clinical review.
AB  - BACKGROUND: Pitted keratolysis is a bacterial infection that affects the plantar
      epidermis. Despite the condition being reported in many countries affecting both
      shod and unshod populations, there is little guidance for clinicians providing
      evidence or best practice guidelines on the management of this often stubborn
      infection. METHODS: Using a structured search of a range of databases, papers
      were identified that reported treatments tested on patients with the condition.
      RESULTS: Most of the literature uncovered was generally of a low level, such as
      case-based reporting or small case series. Studies were focused mainly on the use
      of topical antibiotic agents, such as clindamycin, erythromycin, fusidic acid,
      and mupirocin, often in combination with other measures, such as hygiene advice
      and the use of antiperspirants. From the limited evidence available, the use of
      topical antibiotic agents shows some efficacy in the treatment of pitted
      keratolysis. However, there is currently no suggestion that oral antibiotic drug
      therapy alone is effective in managing the condition. CONCLUSIONS: Currently,
      there is no consensus on the most effective approach to managing pitted
      keratolysis, but a combination of antimicrobial agents and adjunctive measures,
      such as antiperspirants, seems to demonstrate the most effective approach from
      the current literature available.

PMID- 24725040
TI  - Forefoot midsole stiffness affects forefoot and rearfoot kinematics during the
      stance phase of gait.
AB  - BACKGROUND: The forefoot midsole stiffness of the shoe may affect the kinematics
      of the foot segments. We evaluated the effects of two different levels of
      forefoot midsole stiffness on the angular displacement of the forefoot and
      rearfoot in the three planes of motion during the stance phase of gait. METHODS:
      Thirty-six participants walked on a 10-m walkway at their self-selected speed
      wearing shoes having either low or high forefoot midsole stiffness. Three
      dimensional kinematic data of the foot segments were obtained during the stance
      phase of gait using an eight-camera motion analysis system synchronized with a
      force platform. The dependent variables were forefoot and rearfoot total range of
      motion and maximum and minimum angle values in the sagittal, frontal, and
      transverse planes of motion. RESULTS: Reduced forefoot midsole stiffness produced
      significantly greater forefoot total range of motion in the sagittal plane (1.59
      degrees ). The low-stiffness condition also increased the magnitude of the
      forefoot dorsiflexion angles (4.14 degrees ). Furthermore, the low-stiffness
      condition increased the magnitude of the rearfoot inversion (1.21 degrees ) and
      adduction (11.38 degrees ) angles and reduced the rearfoot abduction angle (12.1
      degrees ). CONCLUSIONS: It is likely that reduced stiffness of the forefoot
      midsole stretched the plantar fascia, increasing rearfoot stability during the
      stance phase of gait. Increased muscular contraction may also explain increases
      in rearfoot stability. Therefore, the integrity of the plantar fascia and ankle
      muscles' force and resistance should be considered when choosing a shoe with
      reduced or increased forefoot midsole stiffness for walking.

PMID- 24725041
TI  - Musculoskeletal pain, job satisfaction, depression, and anxiety among spanish
      podiatric physicians.
AB  - BACKGROUND: There is a high prevalence of musculoskeletal complaints related to
      day-to-day work among podiatric physicians. We sought to determine the
      relationships among musculoskeletal pain, job satisfaction, depression, and
      anxiety in Spanish podiatric physicians. METHODS: A convenience sample of 421
      Spanish podiatric physicians was administered a survey that included questions
      about sociodemographic variables, musculoskeletal pain, job satisfaction,
      depression, and anxiety. RESULTS: On average, respondents were found to have a
      high level of pain, a moderate level of job satisfaction, and low-to-moderate
      levels of depression and anxiety. Young single women had the highest levels of
      pain and anxiety. Analysis with the Student t test indicated significant
      differences between the sexes for levels of pain (P < .0001) and anxiety (P <
      .014). Job satisfaction was inversely related to depression and anxiety.
      CONCLUSIONS: These findings, particularly the increased levels of pain, job
      dissatisfaction, anxiety, and depression in young single female podiatrists,
      indicate a need for strategies to reduce the risks posed by the work environment
      in podiatric medicine, thus minimizing the negative psychological and physical
      consequences of participating in the profession.

PMID- 24725042
TI  - Using amniotic membrane allografts in the treatment of neuropathic foot ulcers.
AB  - Neuropathic foot ulcers are a common complication in patients with diabetes.
      These ulcers are often slow to heal and can lead to infection, further tissue
      destruction, osteomyelitis, and amputation. These patients pose a challenge to
      clinicians who must determine the best treatment options while balancing the
      risks, benefits, and costs. Conservative therapies often present disappointing
      results, and a number of newer "biologic bandages" have been developed to better
      assist the healing process. We describe results from diabetic patients with
      neuropathic foot ulcers treated with a new amniotic membrane-based allograft.

PMID- 24725043
TI  - Multicompartment intramuscular hemangioma of the foot: a case study.
AB  - Soft-tissue tumors in the foot include a range of benign and malignant
      pathologies. In the clinical setting, the list of differential diagnoses can be
      exhausting, and the treatment plan is not always straightforward. In this
      article, we present a case of a 22-year-old female with a soft-tissue mass on her
      plantar foot that has been slowly growing since adolescence and is now causing
      increased pain with ambulation. Her pathology results demonstrated an
      intramuscular hemangioma. Intramuscular hemangiomas are rare benign tumors that
      tend to present in youth or early adulthood. Diagnosis is often delayed for
      months to years, depending on the patient's symptoms. Treatment varies from
      conservative to surgical, depending on size, location, and proximity to vital
      structures. Literature on intramuscular hemangiomas is very limited.
      Intramuscular hemangiomas provide a diagnostic and treatment quandary for the
      clinician and must be considered in the differential diagnoses when presented
      with a soft-tissue mass.

PMID- 24725044
TI  - Repositioning buttress internal graft as a modification to distal osteotomy
      bunionectomies.
AB  - The author proposes a novel use of redundant bone resulting from the lateral
      transposition of the first metatarsal head upon the shaft during a distal
      osteotomy bunionectomy. The bone, which is usually discarded, may be transposed
      to the lateral side of the shaft, fixated in place, and used to buttress the
      metatarsal head, thereby increasing the amount of transpostional shift that can
      safely occur with stability. By doing this, one could extend the range of
      intermetatarsal angles suitable to a distal osteotomy.

PMID- 24725046
TI  - Strength in unity.

PMID- 24725045
TI  - A theoretical perspective on running-related injuries.
AB  - The etiology of running-related injuries remains unknown; however, an implicit
      theory underlies much of the conventional research and practice in the prevention
      of these injuries. This theory posits that the cause of running-related injuries
      lies in the high-impact forces experienced when the foot contacts the ground and
      the subsequent abnormal movement of the subtalar joint. The application of this
      theory is seen in the design of the modern running shoe, with cushioning,
      support, and motion control. However, a new theory is emerging that suggests that
      it is the use of these modern running shoes that has caused a maladaptive running
      style, which contributes to a high incidence of injury among runners. The
      suggested application of this theory is to cease use of the modern running shoe
      and transition to barefoot or minimalist running. This new running paradigm,
      which is at present inadequately defined, is proposed to avoid the adverse
      biomechanical effects of the modern running shoe. Future research should
      rigorously define and then test both theories regarding their ability to discover
      the etiology of running-related injury. Once discovered, the putative cause of
      running-related injury will then provide an evidence-based rationale for clinical
      prevention and treatment.

PMID- 24725051
TI  - rTMS deserves a fair chance as a novel treatment for depression.

PMID- 24725052
TI  - The impact of development on the interpretation of movement disorders rating
      scales.

PMID- 24725054
TI  - Complete photocatalytic reduction of CO2 to methane by H2 under solar light
      irradiation.
AB  - Nickel supported on silica-alumina is an efficient and reusable photocatalyst for
      the reduction of CO2 to methane by H2, reaching selectivity above 95% at CO2
      conversion over 90%. Although NiO behaves similarly, it undergoes a gradual
      deactivation upon reuse. About 26% of the photocatalytic activity of Ni/silica
      alumina under solar light derives from the visible light photoresponse. 

PMID- 24725055
TI  - Versatility of a glycosylphosphatidylinositol fragment in forming highly ordered
      polymorphs.
AB  - Glycosylphosphatidylinositols (GPIs) are often attributed with the ability to
      associate with the organized membrane microdomains. GPI fragment 1 forms a highly
      ordered subgel-phase structure characterized by ordering of both headgroups and
      alkyl chains in thin layers. While investigating the driving forces behind the
      formation of these ordered monolayers, we have studied polymorphism of 1 under
      different conditions employing surface-sensitive X-ray diffraction methods. Three
      distinct polymorphs of 1 (I, II, and III) were identified and characterized by
      grazing incidence X-ray diffraction. Polymorphs II (a condensed monolayer
      structure) and III (highly ordered subgel phase) coexist on an 8 M urea solution
      subphase allowing for a detailed thermodynamic and kinetic analysis of the
      processes leading to the formation of these polymorphs. They are enantiotropic
      and can be directly interconverted by changes in temperature or lateral surface
      pressure. As a consequence, polymorph III nuclei of critical size (or larger)
      could be formed by density fluctuations in a multicomponent system, and they
      could continue to exist for a period of time even under conditions that would
      normally not allow for the nucleation of polymorph III. The processes described
      here could also lead to the formation of patches of highly ordered structures in
      a disordered environment of a cell membrane suggesting that GPIs may play a role
      in the formation of such domains. 

PMID- 24725056
TI  - Early lymphocyte recovery at 28 d post-transplant is predictive of reduced risk
      of relapse in patients with acute myeloid leukemia transplanted with peripheral
      blood stem cell grafts.
AB  - Allogeneic hematopoietic cell transplantation (HCT) is potentially curative for
      acute myeloid leukemia (AML). Impact of lymphocyte recovery on post-transplant
      outcomes has been suggested but reports are conflicting. We evaluated the impact
      of lymphocyte recovery at 28 d post-HCT in 191 AML patients using peripheral
      blood stem cells as graft. Patients were divided into those with absolute
      lymphocyte count (ALC) >= 0.5 * 10(9) /L (n = 111, 58%; high ALC group) and those
      with ALC < 0.5 * 10(9) /L (n = 80, 42%; low ALC group), at day 28 post
      transplant. With a median follow-up of 49 months, overall survival (OS) was
      significantly improved in the high ALC group (59% at 3 yr) vs. patients with low
      ALC (40% at 3 yr, P = 0.03). Cumulative incidence of relapse (CIR) was
      significantly lower in the high ALC group (16% at 3 yr) vs. low ALC group (36% at
      3 yr, P = 0.001). Multivariable analysis for CIR demonstrated high ALC group as
      an independent factor decreasing relapse risk (P = 0.03, HR = 0.49, 95% CI = 0.26
      0.92). Multivariable analysis for OS and non-relapse mortality did not
      demonstrate ALC >= 0.5 * 10(9) /L at 28 d post-transplant to be predictive. We
      conclude that lymphocyte recovery with ALC >= 0.5 * 10(9) /L at day 28 post
      transplant is associated with less relapse in AML patients undergoing allogeneic
      peripheral blood HCT, but without survival benefit.

PMID- 24725058
TI  - Complete mitochondrial genome of the birch catkin bug Kleidocerys resedae
      resedae, as the first representative from the family Lygaeidae (Hemiptera:
      Heteroptera: Lygaeoidea).
AB  - Kleidocerys resedae resedae (Panzer, 1797) (Hemiptera: Heteroptera: Lygaeoidea:
      Lygaeidae: Ischnorhynchinae) is one of the destructive insect pests of birch and
      alder trees in Holarctic. Here we sequenced the complete mitochondrial genome of
      this pest, also representing the first mitochondrial genome of the family
      Lygaeidae. This genome is 14,688 bp long, with an A+T content of 76.0%,
      containing 37 typical animal mitochondrial genes and a control region. All genes
      were arranged in the same gene order as most of other Heteropteran species.
      Presently, the length of this mitochondrial genome is the shortest among all
      available Hemipterans, mainly because of its short control region (220 bp). The
      unusual intergenic spacer between tRNA-His and ND4, only shared by Lygaeoidea,
      was also found in K. resedae resedae, which supports that this spacer may be the
      synapomorphy of Lygaeoidea.

PMID- 24725057
TI  - The complete mitochondrial genome sequence of Takifugu flavidus
      (Tetraodontiformes: Tetrodontidae).
AB  - The complete mitochondrial genome of Takifugu flavidus (Tetraodontiformes:
      Tetrodontidae) was obtained in this study. The mitogenome is 16,449 bp in size
      and contains 13 protein-coding genes, 2 rRNA genes, 22 tRNA genes, and 2 non
      coding regions: origin of light-strand replication (OL) and control region (D
      loop). The overall nucleotide composition of the heavy strand was 29.88% A,
      25.81% T, 15.28% G and 29.03% C, with a slight AT bias of 55.69%. Except for ND6
      gene and eight tRNA genes, other genes are encoded on the heavy strand. The
      mitochondrial genome data of T. flavidus should contribute to phylogenetic
      analysis and studies on genetic structure, as well as molecular phylogeny and
      species identification of Tetrodontidae.

PMID- 24725059
TI  - Complete mitochondrial genome of Cervus elaphus songaricus (Cetartiodactyla:
      Cervinae) and a phylogenetic analysis with related species.
AB  - Complete mitochondrial genome of Tianshan wapiti, Cervus elaphus songaricus, is
      16,419 bp in length and contains 13 protein-coding genes, 2 rRNA genes, 22 tRNA
      genes and 1 control region. The phylogenetic trees were reconstructed with the
      concatenated nucleotide sequences of the 13 protein-coding genes using maximum
      parsimony (MP) and Bayesian inference (BI) methods. MP and BI phylogenetic trees
      here showed an identical tree topology. The monopoly of red deer, wapiti and sika
      deer was well supported, and wapiti was found to share a closer relationship with
      sika deer. Tianshan wapiti shared a closer relationship with xanthopygus than
      yarkandensis. Rusa unicolor and Rucervus eldi were given a basal phylogenetic
      position. Our phylogenetic analysis provided a robust phylogenetic resolution
      spanning the entire evolutionary relationship of the subfamily Cervinae.

PMID- 24725060
TI  - Epidemiological profile of naive HIV-1/AIDS patients in Istanbul: the largest
      case series from Turkey.
AB  - The aim of the study was to report the epidemiological profile of HIV-1 positive
      patients from, Istanbul, Turkey, which has one of the lowest HIV-1/AIDS
      prevalences in Europe. The patients were followed by ACTHIV-IST group which was
      established by the Infectious Diseases Departments of five teaching hospitals
      (three university hospitals and two public hospitals) in Istanbul, Turkey. The
      HIV-1 positive patients were added to the standard patient files in all of the
      centers; these files were then transferred to the ACTHIV-IST database in the
      Internet. A total of 829 naiv-untreated HIV-1 positive patients were chosen from
      the database. The number of male patients was 700 (84.4%) and the mean age of the
      patients was 37 years (range, 17-79). In our study group 348 (42%) of the
      patients were married and 318 (38.7%) of the patients were single. The probable
      route of transmission was heterosexual intercourse in 437 (52.7%) patients and
      homosexual intercourse in 256 (30.9%) patients. In 519 (62.6%) patients the
      diagnose was made due to a screening test and in 241 (29.1%) patients, the
      diagnose was made due to an HIV-related/non-related disease. The mean CD4+ T cell
      number in 788 of the patients was 357.8/mm(3) (+/-271.1), and the median viral
      load in 698 of the patients was 100,000 copies/mL (20-9,790,000). In Turkey, the
      number of HIV-1 positive patients is still low and to diagnose with a screening
      test is the most common way of diagnostic route.

PMID- 24725061
TI  - Light-driven hydrogen evolution by BODIPY-sensitized cobaloxime catalysts.
AB  - We report four photocatalytically active cobaloxime complexes for light-driven
      hydrogen evolution. The cobaloxime catalysts are sensitized by different meso
      pyridyl boron dipyrromethene (BODIPY) chromophores, bearing either two bromo- or
      iodo-substituents on the BODIPY core. The pyridine linker between the BODIPY and
      cobaloxime is further modified by a methyl substituent on the pyridine,
      influencing the stability and electronic properties of the cobaloxime catalyst
      and thus the photocatalytic efficiency of each system. Four cobaloxime catalyst
      complexes and three novel BODIPY chromophores are synthesized and characterized
      by absorption, fluorescence, infrared (IR) and nuclear magnetic resonance (NMR)
      spectroscopy, mass spectrometry, and electrochemistry. Crystal structures for the
      BODIPY-cobaloxime complexes 2 and 3 are presented. In contrast to the
      photocatalytically inactive, nonhalogenated reference complex 1, the four newly
      reported molecules are active for photocatalytic hydrogen evolution, with a
      maximum turnover number (TON) of 30.9 mol equiv of H2 per catalyst for the meso
      methylpyridyl 2,6-diiodo BODIPY-sensitized cobaloxime complex 5. We conclude that
      accessing the photoexcited triplet state of the BODIPY chromophore by introducing
      heavy atoms (i.e., bromine or iodine) is necessary for efficient electron
      transfer in this system, enabling catalytic hydrogen generation. In addition,
      relatively electron-donating pyridyl linkers improve the stability of the
      complex, increasing the overall TON for hydrogen production. 

PMID- 24725062
TI  - Copper transport mediated by nanocarrier systems in a blood-brain barrier in
      vitro model.
AB  - Copper (Cu) is a cofactor of various metalloenzymes and has a role in
      neurodegenerative diseases with disturbed Cu homeostasis, for example, in
      Alzheimer's disease (AD) and Menkes disease. To address Cu imbalances, we
      synthesized two different dendritic nanoparticles (NP) for the transport of
      Cu(II) ions across the blood-brain barrier (BBB). The synthesized NPs show low
      toxicity and high water solubility and can stabilize high amounts of Cu(II). The
      Cu(II)-laden NPs crossed cellular membranes and increased the cellular Cu level.
      A human brain microvascular endothelial cell (HBMEC) model was established to
      investigate the permeability of the NPs through the BBB. By comparing the
      permeability * surface area product (PSe) of reference substances with those of
      NPs, we observed that NPs crossed the BBB model two times more effectively than
      (14)C-sucrose and sodium fluorescein (NaFl) and up to 60* better than Evans Blue
      labeled albumin (EBA). Our results clearly indicate that NPs cross the BBB model
      effectively. Furthermore, Cu was shielded by the NPs, which decreased the Cu
      toxicity. The novel design of the core-shell NP enabled the complexation of
      Cu(II) in the outer shell and therefore facilitated the pH-dependent release of
      Cu in contrast to core-multishell NPs, where the Cu(II) ions are encapsulated in
      the core. This allows a release of Cu into the cytoplasm. In addition, by using a
      cellular detection system based on a metal response element with green
      fluorescent protein (MRE-GFP), we demonstrated that Cu could also be released
      intracellularly from NPs and is accessible for biological processes. Our results
      indicate that NPs are potential candidates to rebalance metal-ion homeostasis in
      disease conditions affecting brain and neuronal systems. 

PMID- 24725063
TI  - Why acquiesce? Worker reproductive parasitism in the Eastern honeybee (Apis
      cerana).
AB  - Most societies are vulnerable to rogue individuals that pursue their own
      interests at the expense of the collective entity. Societies often protect
      themselves from selfish behaviour by 'policing', thereby enforcing the interests
      of the collective over those of individuals. In insect societies, for example,
      selfish workers can activate their ovaries and lay eggs, exploiting the
      collective brood rearing system for individual benefit. Policing, usually in the
      form of oophagy of worker-laid eggs, controls selfish behaviour. Importantly,
      once an effective system of policing has evolved, the incentive for personal
      reproduction is lost, and 'reproductive acquiescence' in which ovary activation
      is rare or absent is predicted to evolve. Studies of social Hymenoptera have
      largely supported the prediction of worker 'acquiescence'; workers of most
      species where policing is well developed have inactive ovaries. However, the
      eastern honeybee Apis cerana appears to be an exception. A. cerana colonies are
      characterized by highly efficient policing, yet about 5% of workers have active
      ovaries, even when a queen is present. This suggests that the evolution of
      acquiescence is incomplete in A. cerana. We regularly sampled male eggs and pupae
      from four A. cerana colonies. Workers had high levels of ovary activation overall
      (11.7%), and 3.8% of assignable male eggs and 1.1% of assignable male pupae were
      worker-laid. We conclude that workers with active ovaries lay their eggs, but
      these rarely survive to pupation because of intense policing. We then used our
      findings as well as previously published data on A. cerana and A. mellifera to
      redo the meta-analysis on which reproductive acquiescence theory is based.
      Including data on both species did not affect the relationship between
      effectiveness of policing and levels of worker reproduction. Their inclusion did,
      however, seriously weaken the relationship between relatedness among workers and
      levels of worker reproduction. Our work thus suggests that relatedness among
      workers does not affect the probability that workers will attempt to reproduce,
      but that it is coercion by peers that limits worker reproduction. 

PMID- 24725064
TI  - G-quadruplex on oligo affinity support (G4-OAS): an easy affinity chromatography
      based assay for the screening of G-quadruplex ligands.
AB  - A simple, cheap, and highly reproducible affinity chromatography-based method has
      been developed for the screening of G-quadruplex binders. The tested compounds
      were flowed through a polystyrene resin functionalized with an oligonucleotide
      able to form, in proper conditions, a G-quadruplex structure. Upon cation-induced
      control of the folding/unfolding processes of the immobilized G-quadruplex
      forming sequence, small molecules specifically interacting with the
      oligonucleotide structure were first captured and then released depending on the
      used working solution. This protocol, first optimized for different kinds of
      known G-quadruplex ligands and then applied to a set of putative ligands, has
      allowed one to fully reuse the same functionalized resin batch, recycled for
      several tens of experiments without loss in efficiency and reproducibility. 

PMID- 24725065
TI  - Construction of the N1-C3 linkage stereogenic centers by catalytic asymmetric
      amination reaction of 3-bromooxindoles with indolines.
AB  - The catalytic asymmetric amination reaction of 3-bromooxindoles with indolines
      for the construction of the N1-C3 linkage stereogenic centers has been realized
      for the first time. Moreover, the racemic substrates (3-substituted indolines)
      were also applicable under the same chiral conditions. The newly developed method
      conveniently led to a formal synthesis of (+)-psychotrimine. 

PMID- 24725066
TI  - Protective immunity and use of bortezomib for antibody-mediated rejection in a
      pediatric kidney transplant recipient.
AB  - Standard treatments for AMR-rituximab, intravenous immunoglobulin, and/or
      plasmapheresis-aim to suppress the production and modulate the effect of donor
      specific antibodies and remove them, respectively. Proteasome inhibitors such as
      bortezomib are potent therapeutic agents that target plasma cells more
      effectively than rituximab to reduce measurable donor-specific antibody
      production. Little is known in adults, and no data exist in children about
      effects of proteasome inhibition to treat AMR on protective antibody titers. We
      present a pediatric renal transplant recipient who received bortezomib for
      relatively early AMR and whose antibody titers to measles and tetanus were
      tracked. The AMR was treated successfully, and we noted no clinical decrease in
      the overall level of protective immunity from pretransplant baseline levels at
      almost one yr after AMR treatment cessation. Larger studies will elucidate more
      clearly how proteasome inhibition to treat AMR affects protective immunity in
      pediatric transplant recipients. 

PMID- 24725067
TI  - The beta2 -adrenoceptor agonist terbutaline recovers rat pharyngeal dilator
      muscle force decline during severe hypoxia.
AB  - RATIONALE: Obstructive sleep apnoea syndrome (OSAS) is a debilitating condition
      characterized by recurrent occlusions of the pharyngeal airway during sleep
      accompanied by arterial hypoxaemia. Upper airway muscle dysfunction is implicated
      in the pathophysiology of OSAS. Pharmacological agents that improve muscle
      contractile and endurance properties may have therapeutic value. AIM: We tested
      the hypothesis that the beta(2) -adrenoceptor agonist terbutaline improves rat
      sternohyoid muscle performance especially during hypoxic stress. METHODS:
      Isometric contractile and endurance properties were examined ex vivo in Krebs
      solution at 35 degrees C. Muscles were incubated in tissue baths under hyperoxic
      (95% O(2) /5% CO(2)) conditions in the absence (control) or presence of the
      beta(2) -adrenoceptor agonist terbutaline (1 MUM). In additional experiments
      under hypoxic (95% N(2) /5% CO(2)) conditions, the effects of terbutaline were
      examined in the presence of the beta-adrenoceptor antagonist propranolol (1 MUM).
      RESULTS: Hypoxia significantly impaired sternohyoid force production. Terbutaline
      completely recovered hypoxic depression of force, an effect that was blocked by
      co-application with propranolol. CONCLUSION: The beta(2) -adrenoceptor agonist
      terbutaline completely recovers hypoxic depression of upper airway muscle force.
      beta(2) -adrenoceptor agonists warrant investigation in animal models of OSAS
      reporting upper airway and diaphragm muscle dysfunction.

PMID- 24725068
TI  - For distinguished contributions to psychophysiology: Don C. Fowles.

PMID- 24725069
TI  - Personality interacts with implicit affect to predict performance in analytic
      versus holistic processing.
AB  - Both theoretical approaches and empirical evidence suggest that negative affect
      fosters analytic processing, whereas positive affect fosters holistic processing,
      but these effects are inconsistent. We aim to show that (a) differences in affect
      regulation abilities ("action orientation") and (b) implicit more so than self
      reported affect assessment need to be considered to advance our understanding of
      these processes. Forty participants were asked to verify whether a word was
      correctly or incorrectly spelled to measure analytic processing, as well as to
      intuitively assess whether sets of three words were coherent (remote associates
      task) to measure holistic processing. As expected, implicit but not explicit
      negative affect interacted with low action orientation ("state orientation") to
      predict higher d' performance in word spelling, whereas implicit but not explicit
      positive affect interacted with high action orientation to predict higher d'
      performance in coherence judgments for word triads. Results are interpreted
      according to personality systems interaction theory. These findings suggest that
      affect and affect changes should be measured explicitly and implicitly to
      investigate affect-cognition interactions. Moreover, they suggest that good
      affect regulators benefit from positive affect for holistic processing, whereas
      bad affect regulators benefit from negative affect for analytical processing. 

PMID- 24725070
TI  - Neonatal haemochromatosis with reversible pituitary involvement.
AB  - Neonatal haemochromatosis is a rare alloimmune gestational disease with a high
      mortality. The hallmark of neonatal haemochromatosis is severe neonatal liver
      failure associated with extrahepatic siderosis. Thus far, no pituitary
      dysfunction has been reported to result from the tissue damage associated with
      extrahepatic siderosis. The present report describes a neonate with neonatal
      haemochromatosis and secondary hypothyroidism associated with pituitary iron
      deposition. Both the conditions were successfully treated by ABO-incompatible
      liver transplantation. Pituitary gland dysfunction is another possible
      extrahepatic manifestation of neonatal haemochromatosis, and it is reversible
      after liver transplantation. 

PMID- 24725071
TI  - Reading difficulty is associated with failure to lateralize temporooccipital
      function.
AB  - OBJECTIVE: Studies of focal epilepsy have revealed abnormalities of language
      organization; however, little attention has been paid to disorders of reading in
      this group. We hypothesized that language functional magnetic resonance imaging
      (fMRI) would reveal differences in language organization between focal epilepsy
      patients with and without reading difficulties. METHODS: We conducted language
      fMRI studies of 10 focal epilepsy patients with reading difficulties, 34 focal
      epilepsy patients without reading difficulties, and 42 healthy controls. RESULTS:
      We defined regions of interests on the basis of activation patterns on an
      orthographic lexical retrieval task. Comparison of activations within these ROIs
      on a second Noun-Verb task revealed epilepsy-related effects (relative to healthy
      controls: reduced activation in left inferior frontal cortex), as well as greater
      activation in the right temporooccipital cortex specific to the reading
      difficulty group. SIGNIFICANCE: These findings identify a focal epilepsy effect
      in the left frontal region (present in patients with and without reading
      difficulties), and a functional abnormality specific to the reading difficulty
      group localized to right temporooccipital cortex-a region implicated in
      lexicosemantic processing. Our observations suggest a failure of left hemisphere
      specialization among focal epilepsy patients with reading difficulties.

PMID- 24725072
TI  - Ionic exchange in p-sulfonatocalix[4]arene-mediated formation of metal-ligand
      complexes.
AB  - The effect of alkali and transition metal cations in the formation of host-guest
      complexes with the water-soluble p-sulfonatocalix[4]arene (SC4) was studied using
      2-chloropyridine and Na(+) and Cu(2+) as model guest and model cations,
      respectively. The results obtained from isothermal titration calorimetry and NMR
      experiments provide evidence for the formation of 1:1:1 ternary complexes for
      both cations with Cu(2+) showing positive cooperativity and Na(+) negative
      cooperativity. The formation of ternary complexes comprising transition metal
      cations has been scarcely explored but present high potential for devising
      catalytic systems/models or for enhancing the stability and selectivity of SC4
      complexes. Because transition metal cations are usually present in solution
      together with other SC4 countercations (e.g., Na(+)), a general binding model
      that considers the dynamic formation of all possible complexes (including ionic
      exchange between ternary complexes) is presented. This model allows the
      optimization of the conditions required to selectively form target complexes. 

PMID- 24725073
TI  - Understanding genetic variation - the value of systems biology.
AB  - Pharmacology is currently transformed by the vast amounts of genome-associated
      information available for system-level interpretation. Here I review the
      potential of systems biology to facilitate this interpretation, thus paving the
      way for the emerging field of systems pharmacology. In particular, I will show
      how gene regulatory and metabolic networks can serve as a framework for
      interpreting high throughput data and as an interface to detailed dynamical
      models. In addition to the established connectivity analyses of effective
      networks, I suggest here to also analyze higher order architectural properties of
      effective networks. 

PMID- 24725074
TI  - Does the speaker's voice quality influence children's performance on a language
      comprehension test?
AB  - PURPOSE: A small number of studies have explored children's perception of
      speakers' voice quality and its possible influence on language comprehension. The
      aim of this explorative study was to investigate the relationship between the
      examiner's voice quality, the child's performance on a digital version of a
      language comprehension test, the Test for Reception of Grammar (TROG-2), and two
      measures of cognitive functioning. METHOD: The participants were (n = 86)
      mainstreamed 8-year old children with typical language development. Two groups of
      children (n = 41/45) were presented with the TROG-2 through recordings of one
      female speaker: one group was presented with a typical voice and the other with a
      simulated dysphonic voice. RESULT: Significant associations were found between
      executive functioning and language comprehension. The results also showed that
      children listening to the dysphonic voice achieved significantly lower scores for
      more difficult sentences ("the man but not the horse jumps") and used more self
      corrections on simpler sentences ("the girl is sitting"). CONCLUSION: Findings
      suggest that a dysphonic speaker's voice may force the child to allocate capacity
      to the processing of the voice signal at the expense of comprehension. The
      findings have implications for clinical and research settings where standardized
      language tests are used.

PMID- 24725075
TI  - Impact of two or less missing treatment sessions on tDCS clinical efficacy:
      results from a factorial, randomized, controlled trial in major depression.
AB  - OBJECTIVES: Transcranial direct current stimulation (tDCS) is a neuromodulatory
      intervention with recent clinical trials showing promising results in major
      depression treatment. Although tDCS has some appealing characteristics (e.g., low
      cost, ease of use, and relatively benign profile of adverse effects), one
      important drawback of the technique is the need to deliver consecutive, repeated
      sessions for several weekdays. However, no study investigated whether absences
      during this acute treatment phase impact on tDCS efficacy, and, if so, whether
      absences should be considered dropouts, therefore increasing attrition. MATERIAL
      AND METHODS: To examine this issue, we used data from a randomized, factorial,
      sham-controlled tDCS study that recruited 120 depressed patients. In this trial,
      the acute treatment phase consisted of ten consecutive sessions delivered once
      daily from Monday to Friday; two nonconsecutive missed visits were allowed, with
      extra tDCS sessions being performed to complete the original number of sessions.
      RESULTS: Our main finding was that the procedure of granting one to two absences
      during the acute treatment phase did not impact on tDCS antidepressant efficacy.
      Moreover, out of 103 completers, only 41 (39.8%) patients presented no missing
      visits and 25 (24.3%) presented two absences. These patients did not differ in
      clinical and demographic characteristics; thus, absences were probably
      circumstantial (e.g., traffic congestion, personal obligations). CONCLUSIONS:
      Absences during the acute tDCS treatment phase are common, which support the use
      of flexible schedules in future tDCS trials as to minimize attrition. Also,
      further studies should access whether higher number of absences can compromise
      optimal tDCS efficacy.

PMID- 24725076
TI  - Multistack integration of three-dimensional hyperbranched anatase titania
      architectures for high-efficiency dye-sensitized solar cells.
AB  - An unprecedented attempt was conducted on suitably functionalized integration of
      three-dimensional hyperbranched titania architectures for efficient multistack
      photoanode, constructed via layer-by-layer assembly of hyperbranched hierarchical
      tree-like titania nanowires (underlayer), branched hierarchical rambutan-like
      titania hollow submicrometer-sized spheres (intermediate layer), and
      hyperbranched hierarchical urchin-like titania micrometer-sized spheres (top
      layer). Owing to favorable charge-collection, superior light harvesting
      efficiency and extended electron lifetime, the multilayered TiO2-based devices
      showed greater J(sc) and V(oc) than those of a conventional TiO2 nanoparticle
      (TNP), and an overall power conversion efficiency of 11.01% (J(sc) = 18.53 mA cm(
      2); V(oc) = 827 mV and FF = 0.72) was attained, which remarkably outperformed
      that of a TNP-based reference cell (eta = 7.62%) with a similar film thickness.
      Meanwhile, the facile and operable film-fabricating technique (hydrothermal and
      drop-casting) provides a promising scheme and great simplicity for high
      performance/cost ratio photovoltaic device processability in a sustainable way.

PMID- 24725077
TI  - Vaginal stone formation on top of recurrent tension-free vaginal tape mesh
      erosion.

PMID- 24725079
TI  - How can we make the results of trials and their meta-analyses using continuous
      outcomes clinically interpretable?

PMID- 24725080
TI  - Local, real-time measurement of drying films of aqueous polymer solutions using
      active microrheology.
AB  - Oscillatory microdisk rheometry was applied to evaluate the evolution of the
      viscoelastic properties at the surface of a film of an aqueous solution of
      poly(vinyl alcohol) (PVA) during drying. The drying rate was measured
      concurrently, based upon measurements of the variation of film thickness. A fully
      hydrolyzed PVA solution shows a constant drying rate, while a less hydrolyzed PVA
      solution exhibits a decreased drying rate in the latter part of the drying
      process, which occurred at the same time as an increase of the elastic modulus.
      We suggest that this difference in behavior is a consequence of the fact that
      both the configuration of the PVA molecule and the strength of interaction with
      water depend on the degree to which the PVA is hydrolyzed. The polymer
      concentration at the film surface can be estimated from the measured viscosity at
      the surface for the fully hydrolyzed PVA solution, and this result then can be
      compared with two theoretical calculations: one in which the polymer
      concentration is assumed to remain uniform throughout the film, and the other in
      which the polymer concentration distribution is determined via a one-dimensional
      diffusion model. This comparison suggests that the polymer is first concentrated
      locally near the surface but later in the drying process the distribution of
      polymer becomes increasingly uniform, possibly due to a spontaneously generated
      convective flow inside the film. 

PMID- 24725081
TI  - Differential regulation of steroidogenic enzyme genes by TRalpha signaling in
      testicular Leydig cells.
AB  - Thyroid hormone signaling has long been implicated in mammalian testicular
      function, affecting steroidogenesis in testicular Leydig cells. However, its
      molecular mechanism is not well understood. Here, we investigated the molecular
      action of thyroid hormone receptor-alpha (TRalpha) on mouse testicular
      steroidogenesis. TRalpha/thyroid hormone (T3) signaling differentially affected
      the expression of steroidogenic enzyme genes, mainly regulating their promoter
      activity. TRalpha directly regulated the promoter activity of the cytochrome P450
      17alpha-hydroxylase/C17-20 lyase gene, elevating its expression in the presence
      of T3. TRalpha also indirectly regulated the expression of steroidogenic enzyme
      genes, such as steroidogenic acute regulatory protein and 3beta-hydroxysteroid
      dehydrogenase, by modulating the transactivation of Nur77 on steroidogenic enzyme
      gene promoters through protein-protein interaction. TRalpha enhanced Nur77
      transactivation by excluding histone deacetylases from Nur77 in the absence of
      T3, whereas liganded TRalpha inhibited Nur77 transactivation, likely due to
      interfering with the recruitment of coactivator such as the steroid receptor
      coactivator-1 to Nur77. Together, these findings suggest a role of TRalpha/T3 in
      testicular steroidogenesis and may provide molecular mechanisms for the
      differential regulation of steroidogenic enzyme genes by thyroid hormone.

PMID- 24725082
TI  - Functional roles of the nuclear localization signal of parathyroid hormone
      related protein (PTHrP) in osteoblastic cells.
AB  - PTHrP is an important regulator of bone remodelling, apparently by acting through
      several sequence domains. We here aimed to further delineate the functional roles
      of the nuclear localization signal (NLS) comprising the 88-107 amino acid
      sequence of PTHrP in osteoblasts. PTHrP mutants from a human PTHrP (-36/+139)
      cDNA (wild type) cloned into pcDNA3.1 plasmid with deletion (Delta) of the signal
      peptide (SP), NLS, T(107), or T107A replacing T(107) by A(107) were generated and
      stably transfected into osteoblastic MC3T3-E1 cells. In these cells,
      intracellular trafficking, cell proliferation and viability, as well as cell
      differentiation were evaluated. In these transfected cells, PTHrP was detected in
      the cytoplasm and also in the nucleus, except in the NLS mutant. Meanwhile, the
      PTH type 1 receptor (PTH1R) accumulates in the cytoplasm except for the DeltaSP
      mutant in which the receptor remains at the cell membrane. PTHrP-wild type cells
      showed enhanced growth and viability, as well as an increased matrix
      mineralization, alkaline phosphatase activity, and osteocalcin gene expression;
      and these features were inhibited or abolished in DeltaNLS or DeltaT(107)
      mutants. Of note, these effects of PTHrP overexpression on cell growth and
      function were similarly decreased in the DeltaSP mutant after PTH1R small
      interfering RNA transfection or by a PTH1R antagonist. The present in vitro
      findings suggest a mixed model for PTHrP actions on osteoblastic growth and
      function whereby this protein needs to be secreted and internalized via the PTH1R
      (autocrine/paracrine pathway) before NLS-dependent shuttling to the nucleus
      (intracrine pathway). 

PMID- 24725083
TI  - Estrogen-related receptor gamma serves a role in blood pressure homeostasis
      during pregnancy.
AB  - Persistent hypoxia caused by shallow trophoblast invasion and poor placental
      perfusion may underlie the pathophysiology of preeclampsia, a leading cause of
      maternal and neonatal morbidity and mortality. Previously, we found that estrogen
      related receptor gamma (ERRgamma) serves a critical and O2-dependent role in
      differentiation of human trophoblasts in culture and expression of tissue
      kallikrein and voltage-gated K(+) channels. In this study, we surprisingly
      observed that ERRgamma expression was significantly increased in placentas from
      preeclamptic women compared with that in gestation-matched normotensive women. To
      further investigate a functional role for ERRgamma during pregnancy, we analyzed
      ERRgamma-deficient mice. Maternal systolic blood pressure was significantly
      reduced in pregnant ERRgamma(+/-) females bred to ERRgamma(+/-) males compared
      with that in wild-type (WT) mice and was markedly up-regulated by treatment of WT
      pregnant mice with the ERRgamma agonist DY131. Placentas of ERRgamma(+/-) mice
      manifested increased vascular endothelial growth factor A expression compared
      with that in WT mice. Notably, circulating levels of the antiangiogenic factor,
      soluble fms-like tyrosine kinase-1, were significantly reduced in ERRgamma(+/-)
      pregnant mice as was serum aldosterone. These effects were associated with a
      decrease in maternal adrenal Cyp11b1 (steroid 11beta-hydroxylase) and Cyp11b2
      (aldosterone synthase) expression. In contrast, adrenal Cyp11b1 and Cyp11b2 mRNA
      were increased in pregnant WT mice treated with DY131. Moreover, chromatin
      immunoprecipitation and luciferase reporter assays identified Cyp11b2 as a
      transcriptional target of ERRgamma. Collectively, these findings reveal a
      potential role of ERRgamma in maternal blood pressure homeostasis during
      pregnancy and suggest that aberrant ERRgamma expression may contribute to the
      pathogenesis of preeclampsia. 

PMID- 24725085
TI  - Effect of cellulose nanowhiskers on surface morphology, mechanical properties,
      and cell adhesion of melt-drawn polylactic Acid fibers.
AB  - Polylactic acid (PLA) fibers were produced with an average diameter of 11.2 (+/-
      0.9) MUm via a melt-drawing process. The surface of the PLA fibers was coated
      with blends of cellulose nanowhiskers (CNWs) (65 to 95 wt %) and polyvinyl
      acetate (PVAc). The CNWs bound to the smooth PLA fiber surface imparted
      roughness, with the degree of roughness depending on the coating blend used. The
      fiber tensile modulus increased 45% to 7 GPa after coating with 75 wt % CNWs
      compared with the uncoated PLA fibers, and a significant increase in the fiber
      moisture absorption properties at different humidity levels was also determined.
      Cytocompatibility studies using NIH-3T3 mouse fibroblast cells cultured onto CNWs
      coated PLA surface revealed improved cell adhesion compared with the PLA control,
      making this CNW surface treatment applicable for biomedical and tissue
      engineering applications. Initial studies also showed complete cell coverage
      within 2 days.

PMID- 24725084
TI  - COP9 subunits 4 and 5 target soluble guanylyl cyclase alpha1 and p53 in prostate
      cancer cells.
AB  - Our laboratory previously has identified soluble guanylyl cyclase alpha1
      (sGCalpha1) as a direct target of androgen receptor and essential for prostate
      cancer cell growth via a pathway independent of nitric oxide (NO) signaling. We
      identified the COP9 signalosome subunit 4 (CSN4) as a novel interacting partner
      for sGCalpha1. Importantly, the CSN4-sGCalpha1 interaction inhibits sGCalpha1
      proteasomal degradation. Consistent with this, disruption of CSN4 led to a
      significant decrease in prostate cancer cell proliferation, which was
      significantly but not completely rescued by sGCalpha1 overexpression, opening the
      possibility of an additional target of CSN4. Interestingly, immunoprecipitation
      experiments showed that p53 is found in the CSN4-sGCalpha1 cytoplasmic protein
      complex. However, in contrast to sGCalpha1, p53 protein stability was compromised
      by CSN4, leading to prostate cancer cell survival and proliferation.
      Interestingly, we observed that CSN4 was overexpressed in prostate tumors, and
      its protein level correlates directly with sGCalpha1 and inversely with p53
      proteins, mimicking what was observed in prostate cancer cells. Our data further
      showed that CSN4 silencing decreased CSN5 protein levels and suggest that the
      CSN4 effects on sGCalpha1 and p53 proteins are mediated by CSN5. Lastly, our
      study showed that caseine kinase-2 (CK2) was involved in regulating p53 and
      sGCalpha1 protein stability as determined by both disruption of CK2 expression
      and inhibition of its kinase activity. Collectively, our study has identified a
      novel endogenous CSN4-CSN5-CK2 complex with sGCalpha1and p53 that oppositely
      controls the stability of these 2 proteins and provides prostate cancer cells an
      important mechanism for survival and proliferation. 

PMID- 24725086
TI  - Phosphatidylserine and curcumin act synergistically to down-regulate release of
      interleukin-1beta from lipopolysaccharide-stimulated cortical primary microglial
      cells.
AB  - Microglia, the brain's resident macrophages, contribute to immune surveillance
      and the response to disease and injury. These immune cells play a dual role in
      the nervous system, having both neurotoxic and neuroprotective effects.
      Activation of microglia results in the production of inflammatory molecules and
      neurotoxic factors that often cause or contribute to neurodegenerative diseases.
      Inhibition of neurotoxic microglia activation and consequent inflammatory
      processes may represent an important therapeutic target. Phosphatidylserine (PS),
      an aminophospholipid of plasma membranes, and curcumin, the yellow pigment
      isolated from the rhizome of the turmeric plant, have both been reported to
      suppress microglial activation by reducing pro-inflammatory mediator production
      and release. In this study we analyzed the effects of PS, curcumin, and their
      association on microglial activation induced by the bacterial toxin
      lipopolysaccharide. Primary rat cortical microglial cells were treated with
      increasing concentrations of PS-liposomes and curcumin, alone or in combination,
      and their effects on pro-inflammatory cytokine release from unstimulated and
      lipopolysaccharide-stimulated microglia were evaluated by enzyme-linked
      immunosorbent assay. Isobolographic analysis was performed to investigate the
      effect of PS-liposomes and curcumin combination. PS and curcumin inhibited the
      release of interleukin (IL)-1beta, IL-6, and tumor necrosis factor-alpha induced
      by lipopolysaccharide. Furthermore, PS and curcumin in combination exerted a
      synergistic effect in down-regulating IL-1beta release. These results suggest
      that the association of PS with curcumin could be of potential therapeutic
      utility against diseases associated with microglial activation. 

PMID- 24725087
TI  - Disentangling the intricacies of migraine: a review.
AB  - The etiology of migraine, a neurological disorder, has still not been clearly
      established, although it may be categorized as a headache disorder with specific
      characteristics such as focal neurological symptoms preceding or accompanying the
      headache. Many researchers have suggested genetic predisposition as one of the
      underlying causes of migraine. An insight into the various pathophysiological
      mechanisms such as the role of cortical spreading depression, abnormal brain stem
      activity, trigeminal nerves, calcitonin gene related peptide, nitric oxide and
      serotonin receptors in the development of migraine, has been conferred in the
      present article. The accurate diagnosis of migraine and identification of its
      type is a prerequisite for appropriate therapy. Ample opportunity still exists
      for the improvement in the safety, efficacy and tolerance capacity of the
      currently available antimigraine medications, through the design and development
      of targeted drug delivery system. In the present review, an attempt has been made
      to highlight all the underlying pathophysiological mechanisms of migraine, its
      diagnosis, treatment and therapeutic area to be explored including mitigation of
      biochemical pathways and gene therapy. 

PMID- 24725088
TI  - Pain and bleeding associated with trephine biopsy.
AB  - The study objectives were to determine the intensity and duration of pain,
      factors that may influence pain experience during and after trephine biopsy, and
      to assess bleeding and infectious complications related to the procedure.
      Patients scheduled for trephine biopsy were recruited to the study. Local
      anesthesia was applied in all patients. Pain intensity was recorded twice daily
      by the patients using the numeric rating scale (NRS). Bleeding was graded into
      four grades. Median age of 184 patients was 63 yr. Maximum NRS level was measured
      at time of biopsy (T0); 167 (91%) patients experienced pain at T0. Median (Q1:Q3)
      NRS was 3 (1; 5). Median duration of pain was 36 h. Fourteen patients reported
      pain for more than 7 d. Significant inverse correlation was found between NRS at
      T0 and age. Pain duration at rest correlated with NRS at T0 and age, while pain
      duration in activity correlated with NRS at T0, age, and with body mass index
      (BMI). Mild and moderate bleeding at T0 occurred in 97 (54%) and 18 (10%)
      patients, respectively; no severe bleeding or infectious complications were
      registered. Secondary bleeding occurred in two patients; both required
      hospitalization. In conclusion, the study shows that despite the application of
      local anesthetic, more than 50% of the patients experienced pain of >= 3 points.
      Procedure-related bleeding is mild to moderate and managed by local pressure
      only.

PMID- 24725089
TI  - Post-mortem sporulation of Ceratomyxa shasta (Myxozoa) after death in adult
      Chinook salmon.
AB  - Ceratomyxa shasta (Myxozoa) is a common gastrointestinal pathogen of salmonid
      fishes in the Pacific Northwest of the United States. We have been investigating
      this parasite in adult Chinook salmon ( Oncorhynchus tshawytscha ) in the
      Willamette River, Oregon. In prior work, we observed differences in the pattern
      of development of C. shasta in adult salmon compared to juvenile salmon. Adult
      salmon consistently had large numbers of prespore stages in many of the fish that
      survived to spawn in the fall. However, myxospores were rarely observed, even
      though they were exposed and presumably infected for months before spawning. We
      evaluated the ability of C. shasta to sporulate following fish death because it
      is reported that myxosores are common in carcasses of Chinook salmon. We
      collected the intestine from 30 adult salmon immediately after artificial
      spawning and death (T0). A total of 23 fish were infected with C. shasta based on
      histology, but only a few myxospores were observed in 1 fish by histology.
      Intestines of these fish were examined at T0 and T7 (latter held at 17 C for 7
      days) using quantified wet mount preparations. An increase in myxospore
      concentrations was seen in 39% of these fish, ranging between a 1.5- to a 14.5
      fold increase. The most heavily infected fish exhibited a 4.6-fold increase from
      27,841 to 129,352 myxospores/cm. This indicates, supported by various statistical
      analyses, that under certain conditions presporogonic forms are viable and
      continue to sporulate after death in adult salmon. Considering the life cycle of
      C. shasta and anadromous salmon, the parasite may have evolved 2, non-mutually
      exclusive developmental strategies. In young fish (parr and smolts), the parasite
      sporulates shortly after infection and is released into freshwater from either
      live or dead fish before their migration to seawater, where the alternate host is
      absent. The second strategy occurs in adult salmon, particularly spring Chinook
      salmon, which become infected upon their return to freshwater in the spring or
      early summer. For several months throughout the summer, only prespore stages are
      observed in most fish, even at the time of spawning. But once the fish dies,
      environmental conditions experienced by C. shasta change and viable presporogonic
      stages are induced to sporulate. As the post-spawned fish occur in the upper
      reaches of rivers, the myxospores would be released in a freshwater environment
      that would provide a reasonable opportunity for them to encounter their
      freshwater polychaete hosts, which reside downstream. 

PMID- 24725090
TI  - Catalytic asymmetric alpha-aldol reaction of vinylogous N-heterocyclic carbene
      enolates: formation of quaternary and labile tertiary stereocenters.
AB  - Simple N-heterocyclic carbene (NHC)-enolates are widely studied versatile
      species. However, their vinylogous siblings (i.e., vinylogous NHC-enolates) have
      been much less studied. Here we disclose the first catalytic asymmetric alpha
      aldol reaction of vinylogous NHC-enolates. With trifluoropyruvate as the carbon
      electrophile, the efficient C-C bond formation process displays not only complete
      alpha-regioselectivity but also excellent stereocontrol over the two newly
      established challenging stereocenters (one quaternary and the other labile
      tertiary), furnishing a range of highly enantioenriched beta,gamma-unsaturated
      alpha-fluoroalkylated esters. 

PMID- 24725091
TI  - Selection from parasites favours immunogenetic diversity but not divergence among
      locally adapted host populations.
AB  - The unprecedented polymorphism in the major histocompatibility complex (MHC)
      genes is thought to be maintained by balancing selection from parasites. However,
      do parasites also drive divergence at MHC loci between host populations, or do
      the effects of balancing selection maintain similarities among populations? We
      examined MHC variation in populations of the livebearing fish Poecilia mexicana
      and characterized their parasite communities. Poecilia mexicana populations in
      the Cueva del Azufre system are locally adapted to darkness and the presence of
      toxic hydrogen sulphide, representing highly divergent ecotypes or incipient
      species. Parasite communities differed significantly across populations, and
      populations with higher parasite loads had higher levels of diversity at class II
      MHC genes. However, despite different parasite communities, marked divergence in
      adaptive traits and in neutral genetic markers, we found MHC alleles to be
      remarkably similar among host populations. Our findings indicate that balancing
      selection from parasites maintains immunogenetic diversity of hosts, but this
      process does not promote MHC divergence in this system. On the contrary, we
      suggest that balancing selection on immunogenetic loci may outweigh divergent
      selection causing divergence, thereby hindering host divergence and speciation.
      Our findings support the hypothesis that balancing selection maintains MHC
      similarities among lineages during and after speciation (trans-species
      evolution). 

PMID- 24725092
TI  - Significance of new lung infiltrates in outpatients after lung and heart-lung
      transplantation.
AB  - BACKGROUND: Infection and rejection represent major complications following lung
      transplantation and are often associated with pulmonary infiltrates. The
      differential diagnosis of these infiltrates depends on their timing after
      transplantation. The aim of this study was to characterize lung transplant
      recipients (LTR) presenting with new pulmonary infiltrates. METHODS: A
      retrospective analysis of all LTR and heart-lung transplant recipients attending
      outpatient follow-up at our institution between September 1, 2006 and October 14,
      2011 was performed. All patients presenting with new pulmonary infiltrates on
      chest x-ray who underwent bronchoscopy were included. RESULTS: A total of 913
      patients accounted for 13,156 attendances, with 3,912 bronchoscopies being
      performed. Seventy-eight patients (9%) exhibited new pulmonary infiltrates and
      proceeded to bronchoscopy. Infiltrates occurred at a median 15 (interquartile
      range [IQR] 5-39) months after transplantation. Forty-eight patients (62%) were
      male, and median patient age was 47 (IQR 29-57) years. Subsequent investigation
      revealed pneumonia to be the underlying cause in 63 patients (81%). In the
      remaining patients, chronic lung allograft dysfunction (CLAD) was responsible in
      6 (8%), acute rejection in 5 (6%), and toxic pneumonitis in 4 (5%) patients.
      Overall 1-year survival in LTR presenting with new infiltrates was 97%, compared
      with 96% for all LTR attending our Outpatient Department. CONCLUSIONS: New
      pulmonary infiltrates occurring after the first month in LTR are most likely due
      to infection. Through prompt diagnosis and treatment, early mortality appears
      unaffected. Late mortality remains attributable to CLAD.

PMID- 24725093
TI  - Understanding mixed-mode retention mechanisms in liquid chromatography with
      hydrophobic stationary phases.
AB  - The chromatographic retention mechanisms of two hydrophobic bonded phases,
      octadecyl ethyl-bridged organic/inorganic (BEH-C18) and straight-chain
      perfluorohexylpropyl silica (C6F13), have been investigated by using a homologous
      series of alkyl-benzenes and perfluoroalkyl acids as test compounds in a variety
      of acetonitrile/water mobile phases and at different temperatures. On both
      columns, polar compounds exhibited a characteristic U-shape retention behavior in
      function of acetonitrile amount in the eluent, whereas retention of neutral
      molecules decreased continuously, following an increase of organic modifier, over
      the entire mobile phase range. The dependence of perfluoromethylene selectivity
      upon eluent composition explains the typical reversed-phase behavior (decreasing
      in retention following an increase of acetonitrile in mobile phase) initially
      exhibited by perfluoroalkyl acids, but alone it cannot justify their increasing
      of retention at organic-rich mobile phases (approximately >90% v/v for
      acetonitrile with the C6F13 column and acetonitrile >80% v/v for the BEH-C18
      one). It actually predicts an opposite trend, indicating thus the presence of
      mixed-mode retention mechanisms. Indeed it was found that, at organic-rich mobile
      phases, the transfer from the mobile to the stationary phase of the polar moiety
      of molecules drives retention. This finding has been correlated to the excess
      adsorption isotherm of acetonitrile/water binary mixtures and thus to the
      composition of the stationary phase. At organic-rich mobile phases, in fact,
      stationary phases are characterized by a positive excess of adsorbed water that
      creates an "environment" suitable to the transfer herein of polar groups. 

PMID- 24725094
TI  - Site-specific copper-catalyzed oxidation of alpha-synuclein: tightening the link
      between metal binding and protein oxidative damage in Parkinson's disease.
AB  - Amyloid aggregation of alpha-synuclein (AS) has been linked to the pathological
      effects associated with Parkinson's disease (PD). Cu(II) binds specifically at
      the N-terminus of AS and triggers its aggregation. Site-specific Cu(I)-catalyzed
      oxidation of AS has been proposed as a plausible mechanism for metal-enhanced AS
      amyloid formation. In this study, Cu(I) binding to AS was probed by NMR
      spectroscopy, in combination with synthetic peptide models, site-directed
      mutagenesis, and C-terminal-truncated protein variants. Our results demonstrate
      that both Met residues in the motif (1)MDVFM(5) constitute key structural
      determinants for the high-affinity binding of Cu(I) to the N-terminal region of
      AS. The replacement of one Met residue by Ile causes a dramatic decrease in the
      binding affinity for Cu(I), whereas the removal of both Met residues results in a
      complete lack of binding. Moreover, these Met residues can be oxidized rapidly
      after air exposure of the AS-Cu(I) complex, whereas Met-116 and Met-127 in the C
      terminal region remain unaffected. Met-1 displays higher susceptibility to
      oxidative damage compared to Met-5 because it is directly involved in both Cu(II)
      and Cu(I) coordination, resulting in closer exposure to the reactive oxygen
      species that may be generated by the redox cycling of copper. Our findings
      support a mechanism where the interaction of AS with copper ions leads to site
      specific metal-catalyzed oxidation in the protein under physiologically relevant
      conditions. In light of recent biological findings, these results support a role
      for AS-copper interactions in neurodegeneration in PD. 

PMID- 24725095
TI  - Immunomodulation regulates mesenchymal stem cell-based bone regeneration.
AB  - Mesenchymal stem cell (MSC)-based regenerative medicine represents a promising
      frontier for bone reconstruction. Significant efforts have been devoted to
      clarifying the capacities of MSCs to repair or reconstruct bone tissue. This
      review provides a concise summary of current knowledge pertaining to the possible
      mechanisms of MSC action in the regeneration of bone, with particular focus on
      the interplay between donor MSCs and host immune response in the process of new
      bone regeneration.

PMID- 24725096
TI  - Turn-on phosphorescence by metal coordination to a multivalent terpyridine
      ligand: a new paradigm for luminescent sensors.
AB  - A hexathiobenzene molecule carrying six terpyridine (tpy) units at the periphery
      has been designed to couple the aggregation induced phosphorescence, displayed by
      the core in the solid state, to the metal binding properties of the tpy units.
      Upon Mg(2+) complexation in THF solution, phosphorescence of the hexathiobenzene
      core is turned on. Metal ion coordination yields the formation of a
      supramolecular polymer which hinders intramolecular rotations and motions of the
      core chromophore, thus favoring radiative deactivation of the luminescent excited
      state. Upon excitation of the [Mg(tpy)2](2+) units of the polymeric structure,
      sensitization of the core phosphorescence takes place with >90% efficiency. The
      light-harvesting polymeric antenna can be disassembled upon fluoride ion
      addition, thereby switching off luminescence and offering a new tool for fluoride
      ion sensing. This unique system can, thus, serve as cation or anion sensor. 

PMID- 24725097
TI  - The work of living with a rare cancer: multiple myeloma.
AB  - AIM: To report findings from a qualitative study of the experiences of long-term
      survivors of multiple myeloma. BACKGROUND: Multiple Myeloma is a malignant
      disease of the bone marrow. Until recently, it was rapidly fatal. Although it
      remains incurable, people diagnosed with it are living longer on average, largely
      due to new treatments, some of which have onerous side effects. DESIGN:
      Prospective descriptive study. METHOD: A series of 47 in-depth interviews were
      conducted at 6-12 month intervals over 18 months in 2008-2010 with 10 long-term
      survivors of myeloma and their primary support person. Interviews were analysed
      using the constant comparative method (Grounded Theory). FINDINGS: To adapt to
      the effects of both the disease and ongoing medical treatments, participants
      undertook extensive 'illness work'. Most of this work fell into two broad
      categories. Risk work aimed to mitigate risks to the well-being of both the
      person with myeloma and his/her carer. Emotion work aimed to manage the feelings
      of self and others in a protracted cycle of remission and relapse. CONCLUSION:
      The experience of myeloma is increasingly characterized by issues associated with
      chronic disease and 'survivorship'. It is important for nurses working with
      people with myeloma to understand the overwhelming nature of illness work in this
      context. Nurses can put in place supportive measures to address the two main
      'drivers' of this work: constant risk to well-being of survivors (including
      carers) and the recurrent need to manage emotions in social interactions.

PMID- 24725098
TI  - New technique for open placement of paddle-type spinal cord stimulator electrode
      in presence of epidural scar tissue.
AB  - OBJECTIVES: The objective of this study is to present a novel surgical technique
      for safe placement of paddle-type spinal cord stimulation (SCS) electrode in the
      presence of epidural scar tissue. MATERIALS AND METHODS: We developed a new
      surgical technique for placement of paddle-type SCS electrode in presence of
      epidural scar tissue when conventional placement methods had failed. The
      technique involves creating a laminotomy trough to provide an adequate window for
      dissection of scar tissue to ensure safe placement of the electrode. We have
      applied this technique in eight patients. RESULTS: Safe placement of SCS
      electrode was achieved in all eight patients without any complications. All
      electrodes were placed between T8 and T10 levels, and we were able to place the
      electrodes in the midline and achieve adequate coverage in all cases. CONCLUSION:
      SCS is a widely accepted treatment modality for chronic neuropathic pain.
      Placement of paddle electrode can be challenging, usually because of the presence
      of epidural scar tissue. There have been reported cases of spinal cord injury
      related to paddle electrode placement. We present a novel technique that allows
      for safe placement of a paddle-type SCS electrode in more challenging surgical
      circumstances, including the presence of epidural scar tissue.

PMID- 24725099
TI  - Protective effect of Euterpe oleracea Mart (acai) extract on programmed changes
      in the adult rat offspring caused by maternal protein restriction during
      pregnancy.
AB  - OBJECTIVES: This study examined the effect of acai (Euterpe oleracea Mart.) seed
      extract (ASE) on cardiovascular and renal alterations in adult offspring, whose
      mothers were fed a low-protein (LP) diet during pregnancy. METHODS: Four groups
      of rats were fed: control diet (20% protein); ASE (200 mg/kg per day); and LP (6%
      protein); LP + ASE (6% protein + ASE) during pregnancy. After weaning, all male
      offspring were fed a control diet and sacrificed at 4 months old. We evaluated
      the blood pressure, vascular function, serum and urinary parameters, plasma and
      kidney oxidative damage, and antioxidant activity and renal structural changes.
      KEY FINDINGS: Hypertension and the reduced acetylcholine-induced vasodilation in
      the LP group were prevented by ASE. Serum levels of urea, creatinine and
      fractional excretion of sodium were increased in LP and reduced in LP + ASE. ASE
      improved nitrite levels and the superoxide dismutase and glutathione peroxidase
      activity in LP, with a corresponding decrease of malondialdehyde and protein
      carbonyl levels. Kidney volume and glomeruli number were reduced and glomerular
      volume was increased in LP. These renal alterations were prevented by ASE.
      CONCLUSIONS: Treatment of protein-restricted dams with ASE provides protection
      from later-life hypertension, oxidative stress, renal functional and structural
      changes, probably through a vasodilator and antioxidant activity.

PMID- 24725100
TI  - Electrostatics and charge regulation in polyelectrolyte multilayered assembly.
AB  - We examine the implications of electrostatic interactions on formation of
      polyelectrolyte multilayers, in application to field-effect based biosensors for
      label-free detection of charged macromolecules. We present a quantitative model
      to describe the experimental potentiometric observations and discuss its
      possibilities and limitations for detection of polyelectrolyte adsorption. We
      examine the influence of the ionic strength and pH on the sensor response upon
      polyelectrolyte layer-by-layer formation. The magnitude of potential oscillations
      on the sensor-electrolyte interface predicted upon repetitive adsorption charge
      alternating polymers agrees satisfactorily with experimental results. The model
      accounts for different screening by mobile ions in electrolyte and inside tightly
      interdigitated multilayered structure. In particular, we show that sensors'
      potential oscillations are larger and more persistent at lower salt conditions,
      while they decay faster with the number of layers at higher salt conditions, in
      agreement with experiments. The effects of polyelectrolyte layer thickness,
      substrate potential, and charge regulation on the sensor surface triggered by
      layer-by-layer deposition are also analyzed. 

PMID- 24725103
TI  - Resolving disparity, one more step.

PMID- 24725101
TI  - Aprotic and aqueous Li-O2 batteries.

PMID- 24725102
TI  - Stationary chemical gradients for concentration gradient-based separation and
      focusing in nanofluidic channels.
AB  - Previous work has demonstrated the simultaneous concentration and separation of
      proteins via a stable ion concentration gradient established within a nanochannel
      (Inglis Angew. Chem., Int. Ed. 2001, 50, 7546-7550). To gain a better
      understanding of how this novel technique works, we here examine experimentally
      and numerically how the underlying electric potential controlled ion
      concentration gradients can be formed and controlled. Four nanochannel geometries
      are considered. Measured fluorescence profiles, a direct indicator of ion
      concentrations within the Tris-fluorescein buffer solution, closely match depth
      averaged fluorescence profiles calculated from the simulations. The simulations
      include multiple reacting species within the fluid bulk and surface wall charge
      regulation whereby the deprotonation of silica-bound silanol groups is governed
      by the local pH. The three-dimensional system is simulated in two dimensions by
      averaging the governing equations across the (varying) nanochannel width,
      allowing accurate numerical results to be generated for the computationally
      challenging high aspect ratio nanochannel geometries. An electrokinetic circuit
      analysis is incorporated to directly relate the potential drop across the
      (simulated) nanochannel to that applied across the experimental chip device
      (which includes serially connected microchannels). The merit of the thick double
      layer, potential-controlled concentration gradient as a particle focusing and
      separation tool is discussed, linking this work to the previously presented
      protein trapping experiments. We explain why stable traps are formed when the
      flow is in the opposite direction to the concentration gradient, allowing
      particle separation near the low concentration end of the nanochannel. We predict
      that tapered, rather than straight nanochannels are better at separating
      particles of different electrophoretic mobilities.

PMID- 24725104
TI  - Ethics and the WHO "International Code of Marketing of Breast-milk Substitutes".

PMID- 24725105
TI  - Privileged structures as peptide backbone constraints: polymer-supported
      stereoselective synthesis of benzimidazolinopiperazinone peptides.
AB  - A molecular scaffold comprising a privileged structure was designed and
      synthesized to serve as a peptide backbone conformational constraint. The
      synthesis of highly functionalized 2,3,10,10a-tetrahydrobenzo[4,5]imidazo[1,2
      a]pyrazin-4(1H)-ones on a solid-phase support was performed via a tandem N-acyl-N
      aryliminium ion cyclization-nucleophilic addition reaction. The synthesis
      proceeded with full stereocontrol of the newly formed stereogenic center.
      Conventional and microwave-assisted syntheses were compared with respect to
      efficiency and the optical integrity of the target compounds. Significant
      epimerization was observed during acylation with (S)- and (R)-2-bromopropionic
      acids under microwave conditions. 

PMID- 24725106
TI  - Role of ictal baseline shifts and ictal high-frequency oscillations in stereo
      electroencephalography analysis of mesial temporal lobe seizures.
AB  - OBJECTIVE: To assess the role of ictal baseline shifts (IBS) and ictal high
      frequency oscillations (iHFOs) in intracranial electroencephalography (EEG)
      presurgical evaluation by analysis of the spatial and temporal relationship of
      IBS, iHFOs with ictal conventional stereo-electroencephalography (icEEG) in
      mesial temporal lobe seizures (MTLS). METHODS: We studied 15 adult patients with
      medically refractory MTLS who underwent monitoring with depth electrodes. Seventy
      five ictal EEG recordings at 1,000 Hz sampling rate were studied. Visual
      comparison of icEEG, IBS, and iHFOs were performed using Nihon-Kohden Neurofax
      systems (acquisition range 0.016-300 Hz). Each recorded ictal EEG was analyzed
      with settings appropriate for displaying icEEG, IBS, and iHFOs. RESULTS: IBS and
      iHFOs were observed in all patients and in 91% and 81% of intracranial seizures,
      respectively. IBS occurred before (22%), at (57%), or after (21%) icEEG onset. In
      contrast, iHFOs occurred at (30%) or after (70%) icEEG onset. The onset of iHFOs
      was 11.5 s later than IBS onset (p < 0.0001). All of the earliest onset of IBS
      and 70% of the onset of iHFOs overlapped with the ictal onset zone (IOZ).
      Compared with iHFOs, interictal HFOs (itHFOs) were less correlated with IOZ. In
      contrast to icEEG, IBS and iHFOs had smaller spatial distributions in 70% and
      100% of the seizures, respectively. An IBS dipole was observed in 66% of the
      seizures. Eighty-seven percent of the dipoles had a negative pole at the
      anterior/medial part of amygdala/hippocampus complex (A-H complex) and a positive
      pole at the posterior/lateral part of the A-H complex. SIGNIFICANCE: The results
      suggest that evaluation of IBS and iHFOs, in addition to routine icEEG, helps in
      more accurately defining the IOZ. This study also shows that the onset and the
      spatial distribution of icEEG, IBS, and iHFOs do not overlap, suggesting that
      they reflect different cellular or network dynamics.

PMID- 24725107
TI  - Surgical skills of specialty trainees in emergency gynaecological laparoscopic
      procedures: a national UK survey.
AB  - A web-based survey was e-mailed to all specialty trainees ST Years 3-7 (n = 773)
      to assess their competence in emergency laparoscopic procedures. The trainees
      were asked about their competence level in a diagnostic laparoscopy; a
      salpingectomy; a salpingotomy; and an oophorectomy/cystectomy for adnexal
      torsion. Subsequently, they were asked how they would manage a tubal ectopic
      pregnancy with contralateral tubal disease. We received 202 responses (26%) and
      of these: 79% of trainees can perform a diagnostic laparoscopy independently; 32%
      can perform a salpingectomy and 12% can perform a salpingotomy independently; 14%
      can manage an adnexal torsion without supervision.

PMID- 24725108
TI  - Predictors of access to sex education for children with intellectual disabilities
      in public schools.
AB  - Data from the National Longitudinal Transition Study-2 ( SRI International, 2002
      ) were analyzed to identify variables that predicted whether individuals with
      intellectual disability (ID) received sex education in public schools across the
      United States. Results suggested that individuals receiving special education
      services without ID were only slightly more likely to receive sex education than
      students with mild ID (47.5% and 44.1%, respectively), but the percentage of
      students with moderate to profound ID that received sex education was
      significantly lower (16.18%). Analysis of teacher opinions and perceptions of the
      likelihood of the students benefiting from sex education found that most teachers
      indicated that students without ID or with mild ID would benefit (60% and 68%,
      respectively), but the percentage dropped to 25% for students with moderate to
      profound ID. Finally, across all students, the only significant demographic
      variable that predicted receipt of sex education was more expressive
      communication skills. Results are discussed in terms of ensuring equal access to
      sex education for students with ID in public schools.

PMID- 24725109
TI  - Family perspectives on a successful transition to adulthood for individuals with
      disabilities.
AB  - When researchers evaluate adult outcomes for individuals with intellectual and/or
      developmental disabilities (IDD), the perspective of families is not always
      considered. Parents of individuals with IDD (N  =  198) answered an online survey
      about their definition of a successful transition to adulthood. Content analysis
      was used to describe themes and ideas present in the responses. Rather than
      focusing only on developmental tasks of adulthood, such as living independently,
      being competitively employed, and maintaining friendships, responses reflected a
      more varied and dynamic view of success in adulthood, taking into account the fit
      between the person with IDD and his or her environment. As services are developed
      and implemented for adults with IDD, it is important to consider the full range
      of goals that families have for their son or daughter's successful transition to
      adulthood.

PMID- 24725110
TI  - Family experience in a regional participant contact registry for research on
      intellectual disability.
AB  - Participant recruitment is one of the most significant challenges in research on
      intellectual disability (ID). One potential solution is to develop a participant
      contact registry, which allows the researcher to contact participants directly
      rather than recruiting through multiple schools or service agencies. The authors
      describe the development of one such registry and results of a survey of registry
      families. Results suggest that families joined the registry to help others, they
      hope research in the ID field improves the daily lives of individuals with ID and
      their families, and they find research participation to be a positive experience.
      However, logistic concerns can be an important barrier to their research
      participation, and they would like more information about the research study both
      before and after participating.

PMID- 24725111
TI  - Acute bouts of assisted cycling improves cognitive and upper extremity movement
      functions in adolescents with Down syndrome.
AB  - The aim of this study was to examine the effectiveness of 2 modes of exercise on
      cognitive and upper extremity movement functioning in adolescents with Down
      syndrome (DS). Nine participants randomly completed 3 interventions over 3
      consecutive weeks. The interventions were: (a) voluntary cycling (VC), in which
      participants cycled at their self-selected pedaling rate; (b) assisted cycling
      (AC), in which the participants' voluntary pedaling rates were augmented with a
      motor to ensure the maintenance of 80 rpm; and (c) no cycling (NC), in which the
      participants sat and listened to music. Manual dexterity improved after AC, but
      not after VC or NC. Measures of cognitive function, including reaction time and
      cognitive planning, also improved after AC, but not after the other
      interventions. Future research will try to uncover the mechanisms involved in the
      behavioral improvements found after an acute bout of assisted cycling in
      adolescents with DS.

PMID- 24725112
TI  - Evaluating representativeness and cancer screening outcomes in a state department
      of developmental services database.
AB  - Though it is widely recognized that people with intellectual and developmental
      disabilities (IDD) face significant health disparities, the comprehensive data
      sets needed for population-level health surveillance of people with IDD are
      lacking. This paucity of data makes it difficult to track and accurately describe
      health differences, improvements, and changes in access. Many states maintain
      administrative health databases that, to date, have not been widely used for
      research purposes. In order to evaluate the feasibility of using administrative
      databases for research purposes, the authors attempted to validate Massachusetts'
      administrative health database by comparing it to a large safety net hospital
      system's patient data regarding cancer screening, and to the state's service
      enrollment tables. The authors found variable representativeness overall; the sub
      population of adults who live in 24-hr supported residences were better
      represented than adults who live independently or with family members. They also
      found a fairly low false negative rate for cancer screening data as compared with
      the "gold standard" of hospital records. Despite some limitations, these results
      suggest that state-level administrative databases may represent an exciting new
      avenue for health research. These results should lend context to efforts to study
      cancer and health screening variables using administrative databases. The present
      study methods may also have utility to researchers in other states for critically
      evaluating other state IDD service databases. This type of evaluation can assist
      researchers in contextualizing their data, and in tailoring their research
      questions to the abilities and limitations of this kind of database.

PMID- 24725113
TI  - Family caregivers of adults with intellectual and developmental disabilities:
      outcomes associated with U.S. services and supports.
AB  - Individuals with intellectual and developmental disabilities (IDD) in the U.S.
      predominantly live with their family caregivers. As care delivery and support
      systems vary widely globally, consideration of caregiver outcomes specifically in
      the U.S. context is needed. A systematic literature review was conducted to
      identify U.S. family caregiver outcomes and their association with existing
      services and supports for family caregivers of adults with IDD. Twenty-four
      articles were compiled using the PubMed, Web of Knowledge, PsychInfo, and CINAHL
      databases. Studies report economic, mental, and physical health outcomes from
      caregiving roles. The need for comprehensive caregiver assessment is discussed.
      Understanding and responding to the changing needs of family caregivers is vital
      to the U.S. disability service system to effectively prioritize formal resources
      and services.

PMID- 24725116
TI  - Faster acquisition of conditioned fear to fear-relevant than to nonfear-relevant
      conditional stimuli.
AB  - Prepared learning theory posits that prepared associations are acquired rapidly
      and resist extinction. Although it has been shown repeatedly that prepared
      associations resist extinction, there is currently little evidence to support the
      proposal of faster acquisition. The current study provides such evidence using a
      within-subjects conditioning procedure with a 50% reinforcement schedule.
      Participants were presented with pictures of four animals, two fear-relevant
      (snake, spider) and two nonfear-relevant (fish, bird), one of each paired with an
      unpleasant electrotactile stimulus on 50% of the trials during acquisition.
      Differential electrodermal responding was observed within the first two blocks of
      acquisition for fear-relevant but not for nonfear-relevant conditional stimuli,
      confirming the prediction that prepared associations are acquired faster than
      nonprepared associations. 

PMID- 24725117
TI  - Comparison of anatomical locations of cutaneous melanoma in men and women: a
      population-based study in France.
AB  - BACKGROUND: Identification of differences in melanoma location between the sexes
      could lead to sex-specific preventive measures. OBJECTIVES: To compare precise
      melanoma location and side in men and women. METHODS: The location of 1542
      incident melanomas diagnosed during the period 2004-2011 in the French Champagne
      Ardenne region (1.3 million inhabitants) was recorded using a regional registry
      and questionnaires sent to physicians. Men and women were compared for frequency
      of tumours on the head and neck; trunk; upper limb; lower limb; hand and foot.
      For each location, more precise sublocations were recorded. The laterality (right
      vs. left) was studied for head/neck and limb tumours. RESULTS: Melanomas
      predominated on the lower limb in women (32.2% vs. 9.3% in men; P < 0.01) and on
      the trunk in men (41.8% vs. 14.9%; P < 0.01), while the proportion of upper limb
      and head/neck tumours was similar in both sexes. Hand and foot melanomas
      predominated in women (10.3% vs. 6.3%; P < 0.01), with a sex-related distribution
      between sublocations. Within the head and neck location, 75.1% of tumours in
      women were located in the central area vs. 53.7% in the peripheral area in men (P
      < 0.01). Head and neck melanomas were more frequently right-sided in women and
      left-sided in men (P = 0.04), with the left/right ratio reaching 1.58 in men vs.
      0.61 in women for peripheral tumours (P < 0.01). No difference in laterality was
      observed for other locations. CONCLUSIONS: Sex differences in occupational and
      leisure time ultraviolet exposure, clothing (including shoes), hairstyle, and
      side and photo exposure in cars could explain these results. General preventive
      messages could be completed by sex-specific advice for melanoma prevention.

PMID- 24725118
TI  - Transport and killing mechanism of a novel camptothecin-deoxycholic acid derivate
      on hepatocellular carcinoma cells.
AB  - Abstract Camptothecin-20(s)-O-glycine ester-[N-(3'alpha, 12'alpha-dihydroxy-24'
      carbonyl-5'beta-cholan)] (A2), 10-(3'alpha,12'alpha-dihydroxy-5'beta-cholan-24'
      carboxyl)-(20 s)-camptothecin (C2), and 10-O-(3-O-(3'alpha, 12'alpha-dihydroxy
      24'-carbonyl-5'beta-cholan)-propyl)-(20S)-camptothecin (D2) are novel
      camptothecin-deoxycholic acid analogues. MTT assays were performed to assess the
      anticancer activity of these compounds against hepatocellular carcinoma SMMC
      7721, breast carcinoma MCF-7, and colorectal carcinoma HCT-116 cells. A2 had a
      high killing ability on SMMC-7721 cells selectively, but C2 and D2 did not
      exhibit selectivity with regard to SMMC-7721 killing. Uptake assays were
      performed in an effort to elucidate the transport mechanisms of A2 into SMMC-7721
      cells. A2 increased the mRNA expression of OATP1B3 (an organic anion-transporting
      polypeptide) and uptake of A2 was inhibited by rifampin (inhibitor of OATP1B3),
      which indicated that the transporter-mediated transport of A2 was mediated by
      OATP1B3. In addition, according to the western blot and apoptosis assays, we
      found that A2 killed SMMC-7721 cells by inducing cell apoptosis mainly via an AIF
      (apoptosis-inducing factor) pathway and a caspase-dependent mitochondria
      apoptosis pathway. 

PMID- 24725119
TI  - Evaluation of Bacteroides fragilis GB-124 bacteriophages as novel human
      associated faecal indicators in the United States.
AB  - Phages infecting human-associated Bacteroides fragilis (GB-124 phages) have been
      employed in the European Union (EU) to identify human faecal pollution, but their
      utility for the United States was unclear. Primary sewage samples were collected
      seasonally from seven wastewater treatment plants (WWTP) across the continental
      United States, and more time-intensive sampling was conducted at local WWTPs. All
      samples were assayed for plaque-forming units (PFU) of GB-124 phages, somatic and
      FRNA-specific coliphages, as well as adenoviruses (by quantitative PCR [qPCR]).
      Animal faecal samples (>250) from 14 different species were tested for the
      presence of the three phage groups. GB-124 phages were consistently detected in
      sewage (10-10(2) PFU ml(-1) ), but not in animal faeces. While density estimates
      of both coliphages in sewage were approximately one order of magnitude higher
      than GB-124 phages, they were both randomly detected in animal faecal samples
      (10(2) -10(5) g(-1) dry weight). Stability of all three phages was inversely
      proportional to temperature; persistence was greatest at 5 degrees C compared to
      20 and 35 degrees C, where no phages were detectable after a week. In summary, GB
      124 phages appear to be a feasible alternative indicator organism and benefit
      from being sewage associated, while providing an inexpensive detection technique
      for infectious virions. SIGNIFICANCE AND IMPACT OF THE STUDY: Bacteroides
      fragilis GB-124 phages appear to be restricted to human sewage sources in the
      United States, being absent from 264 animal faecal samples from 14 different
      species and present in approx. 90% (34/38) of primary sewage effluent samples
      collected across the country. Although somatic and F-specific coliphages were
      present in sewage samples at higher densities, unlike GB-124 phages, both
      coliphage types were also detected in animal faecal samples. Hence, GB-124 phages
      may prove to be a useful novel indicator group for human faecal pollution in the
      continental United States.

PMID- 24725120
TI  - Investigation into the verification of the Synapsys videonystagmography (VNG)
      Ulmer calibration system.
AB  - OBJECTIVE: To assess the accuracy and stability of the Synapsys VNG Ulmer
      calibration system when the goggles and infrared camera are repositioned, and the
      accuracy of the equipment's geometric calibration system. DESIGN: Prospective
      data collection involved participants conducting the system's horizontal
      calibration test. Eye measurements were then recorded for a 60 degrees  deviation
      (looking from 30 degrees  right to -30 degrees  left) and repeated after the
      goggles and infrared camera were removed/repositioned. Participants' eye
      measurements were also recorded after the geometric calibration had been
      activated. STUDY SAMPLE: Twenty-two participants with no history of visual or
      vestibular pathology were recruited for this study. RESULTS: No significant
      differences were found when the goggles were removed and replaced (p = 0.21);
      when the infrared camera was repositioned within the goggles (p = 0.50); or when
      the goggles were removed and the camera repositioned (p = 0.18) after horizontal
      calibration. A significant difference was found during the assessment of
      geometric calibration (p < 0.01). CONCLUSIONS: Calibration is not affected by
      removal or repositioning of the goggles and/or infrared camera within the
      goggles, therefore suggesting recalibration may not be necessary. Caution should
      be exercised when using the equipment's geometric calibration and should only be
      used when the patient is unable to conduct the system's horizontal calibration
      test.

PMID- 24725122
TI  - Increased expression of MUC-1 has close relation with patient survivor in high
      grade salivary gland mucoepidermoid carcinoma.
AB  - PURPOSE: High-grade mucoepidermoid carcinoma (MEC) is an infrequent malignant
      neoplasm originates most commonly in the salivary glands with poor prognosis.
      Thus far, there is little knowledge on MUC-1 expression in high-grade MEC or how
      it may relate to patient survival. The aim of this study was to determine the
      extent of MUC-1 expression in high-grade MEC and correlate expression with clinic
      outcome. METHODS: Surgical specimens from 62 cases of primary high-grade MEC and
      10 cases of normal salivary gland tissue were examined by immunohistochemistry.
      The relationship between MUC-1 expression and the clinicopathological data and
      patient survival was analyzed. RESULTS: The disease-free survival rates were
      54.6% (3 years) and 37.7% (5 years) for high-grade MEC patients. Patient who with
      primary location at submandibular gland have the worst prognosis (P = 0.042) in
      comparing with other sites. High expression of MUC-1 in high-grade MEC was
      significantly correlated with lymphatic/regional metastasis (P = 0.003) and
      clinic stage (P = 0.02), and high expression of MUC-1 (>75%) was confirmed to be
      significant independent prognostic factors in high-grade MEC patients [HR 2.929
      (95% CI 1.246-6.881); P < 0.0137]. CONCLUSIONS: The findings suggest that high
      levels of MUC-1 expression may be a potential marker for worse outcome in high
      grade MEC and could be used as a new molecule target to improve outcomes for
      these patients in the future.

PMID- 24725123
TI  - Polymyxin use as a risk factor for colonization or infection with polymyxin
      resistant Acinetobacter baumannii after liver transplantation.
AB  - INTRODUCTION: Acinetobacter baumannii is a leading agent of healthcare-associated
      infection. The objective of this study was to evaluate cases of colonization or
      infection with polymyxin-resistant A. baumannii (PRAB) in liver transplant
      recipients and to identify the risk factors for the acquisition of PRAB. METHODS:
      We evaluated all patients undergoing liver transplantation (LT) between January
      and November of 2011. The exclusion criterion was death within the first 72 h
      after transplant. Patients were screened for PRAB through weekly rectal and
      inguinal swabs during their stay in the intensive care unit (ICU) and at ICU
      discharge. Patients who came from other hospitals or had been treated in the
      emergency room for >72 h were screened at ICU admission. The minimum inhibitory
      concentrations (MICs) for polymyxins were determined by broth microdilution, and
      clonality was determined by pulsed-field gel electrophoresis. The stepwise
      logistic regression was used to identify risk factors related to acquisition of
      PRAB, and Cox forward regression used to identify risk factors for 60-day
      mortality. RESULTS: We evaluated 65 patients submitted to LT, among whom PRAB was
      isolated in 7, 4 of whom developed infection. The MICs for polymyxin E ranged
      from 16 to 128 mg/mL. All patients with PRAB required dialysis. The median time
      of polymyxin use before PRAB isolation was 21 days. These 4 included 1 case of
      primary bloodstream infection (BSI), which was treated with the carbapenem
      polymyxin combination; 1 case of surgical site infection, which was treated with
      gentamicin, polymyxin, ampicillin-sulbactam, and tigecycline; and 2 cases of
      pneumonia, treated with the combination of carbapenem-polymyxin. In the case of
      BSI and in 1 of the cases of pneumonia, the treatment was considered successful.
      Mortality was 71% among the cases, compared with 33% among the non-cases.
      CONCLUSION: In the final model of the survival analysis, PRAB colonization or
      infection after LT was independently associated with mortality. One predominant
      clone was identified. The only risk factor identified in the multivariate
      analysis was polymyxin use. PRAB was an agent with high mortality, and the most
      important risk factor associated with colonization or infection for such
      bacterium was polymyxin use.

PMID- 24725124
TI  - Commentary: WNT-erizing against neuropathic pain.

PMID- 24725125
TI  - Sulfuryl chloride as an efficient initiator for the metal-free aerobic cross
      dehydrogenative coupling reaction of tertiary amines.
AB  - A metal-free cross-dehydrogenative (CDC) reaction of tertiary amines was
      developed using a catalytic amount of sulfuryl chloride (SO2Cl2) under mild
      aerobic conditions. On the basis of the nature of SO2Cl2, it was assumed that the
      reagent acts as a radical initiator to induce the metal-free CDC reaction via a
      radical-initiated autoxidation mechanism. 

PMID- 24725126
TI  - Treatment of advanced breast cancer with chinese medicinal herbs of Fei
      decoction: a case report.
AB  - A 46-year-old female underwent surgery for cancer of the right breast mammary
      (T3N2M0) in Sep 2010. Following post surgery, adjuvant chemotherapy of CAF
      regimens (cyclophosphamide+adriamycin+fluorouracil) was administered. Two years
      later, multiple pulmonary and skeletal metastatic lesions had been found by CT
      (computerized tomography) and ECT (emission computed tomograph) imaging. She
      received the treatment of second-line chemotherapy regimens of GP (cisplatin +
      gemcitabine). In the meantime, we administered Chinese traditional herb drugs
      (Fei Decoction, mixed a variety of effective herbal components) to help her
      recover from the poor condition. After taking the Chinese herbs for 2 months, the
      tumour marker (CEA, CA15-3) dramatically decreased, resulting in the normal
      range. Both lung and bone metastatic sites reduced according to CT and ECT
      imaging, and the patient felt free from the complaint of pulmonary and cardiac
      discomfort. Over time, the quality of life has been greatly improved, we have
      managed to prolong the PFS (progression-free-survival) and TTP (time-to
      progression) from the onset to date. CTM (Chinese traditional medicine) considers
      human body as a dynamic platform in which all organs are correlative and bind
      each other. Relationship between heart, liver, spleen, lung and kidney is like an
      interlink between mother and son, and runs in cycle as a circle. In the course of
      this combined treatment, we showed that Chinese herbal medicine played an
      important role in the therapy of breast cancer. Chinese herbs might be an
      additional choice with their better benefits and tolerability in the treatment of
      recurrent breast cancer. 

PMID- 24725127
TI  - Enhancement of contractile force generation of artificial skeletal muscle tissues
      by mild and transient heat treatment.
AB  - Artificial skeletal muscle tissues composed of cells are expected to be used for
      applications of regenerative medicine and drug screening. Generally, however, the
      physical forces generated by tissue-engineered skeletal muscle are lower than
      those of skeletal muscle tissues found in the body. Local hyperthermia is used
      for many diseases including muscle injuries. It was recently reported that mild
      heat treatment improved skeletal muscle functions. In this study, we investigated
      the effects of mild heat treatment on the tissue-engineered skeletal muscle
      tissues in vitro. We used magnetite cationic liposomes to label C2C12 myoblast
      cells magnetically, and constructed densely packed artificial skeletal muscle
      tissues by using magnetic force. Cell culture at 39 degrees C promoted the
      differentiation of myoblast cells into myotubes. Moreover, the mild and transient
      heat treatment improved the contractile properties of artificial skeletal muscle
      tissue constructs. These findings indicate that the culture method using heat
      treatment is a useful approach to enhance functions of artificial skeletal muscle
      tissue. 

PMID- 24725128
TI  - Rare genetic diseases with human lean and/or starvation phenotype open new
      avenues for obesity and type II diabetes treatment.
AB  - Treatments of obesity and type II diabetes target often gene functions involved
      in appetite-satiety, fat and carbohydrate metabolism or thermogenesis. None of
      these, have provided efficient drug therapy due to a large number of genes
      involved in weight and energy management, the redundancy of biochemical pathways
      and the environmental factors. Here I discuss a new approach based on studies of
      genes/proteins that are associated with human "lean or starvation" phenotype that
      became very rare in the course of evolution. This approach has led to the
      identification of the congenital enteropeptidase deficiency gene and the
      Anderson's Disease gene as a potential targets for obesity and type II diabetes
      treatment. The advantages of these targets are: 1) they are expressed exclusively
      in the intestine; 2) they are peripheral targets as opposed to systemic targets;
      3) they are not redundant targets. These targets open new hopes for the
      development of novel drugs for the treatment of common metabolic syndrome. 

PMID- 24725129
TI  - In vitro and in vivo evaluation of antitumor drug-loaded aptamer targeted single
      walled carbon nanotubes system.
AB  - OBJECTIVE: A multifunctional tumor-targeting drug delivery system employing
      single-walled carbon nanotubes (SWCNT) as drug carriers, AS1411 as targeting
      ligand and doxorubicine (DOX) as a model chemotherapy drug was constructed.
      METHODS: Firstly, SWCNT were modified with F68 (4.0 mg/ml) by ultrasonic
      dispersing technology due to the action of hydrophobic force and Van der Waals
      force, endowing SWCNT water dispersions and biocompatibility. Meanwhile, DOX
      could be easily absorbed on the surface of SWCNT by the &#960;-&#960; stacking,
      electrostatic adsorption and hydrophobic interactions. Finally, AS1411 was
      attached to the surface of DOX-SWCNT by the pi-pi stacking and electrostatic
      adsorption to obtain a tumor-targeting delivery system. Cellular uptake, anti
      tumor effect in vitro and in vivo, cell cycle and apoptosis and biodistribution
      of AS1411-DOX-SWCNT were investigated, compared with the DOX solution.
      CONCLUSION: This AS1411-mediated DOX-loaded SWCNT (AS1411-DOX-SWCNT) delivery
      system not only retained both optical properties of SWCNT and cytotoxicity of DOX
      but also could accumulate in tumors, which facilitated combination of
      chemotherapy and photothermal therapy. AS1411-DOX-SWCNT could effectively promote
      DOX cellular uptake and then increase intracellular accumulation as a targeting
      delivery system. AS1411-DOX-SWCNT by NIR laser excited could trigger S phase
      arrest and the late stage apoptotic on PC3 cancer cells. The investigation in
      vivo further confirmed that this system possessed higher tumor targeting capacity
      and antitumor efficacy than DOX, especially with NIR laser irradiation.

PMID- 24725130
TI  - The current status of novel PET radio-pharmaceuticals in radiotherapy treatment
      planning of glioma.
AB  - Malignant glioma is a primary tumor of the central nervous system, representing a
      major cause of mortality in a young, productive subset of population. The
      management of this neoplasm requires aggressive treatments, including
      radiotherapy. Accurate imaging plays a central role in treatment planning process
      with curative intent based on radiation therapy. In order to maximize the
      radiation dose to the tumor and to minimize the damage to the normal surrounding
      tissue, a reliable identification of viable tumor margins is indeed required. The
      use of PET in the treatment planning process has become more promising over the
      years, although many important questions must be addressed. The aim of this
      article is to critically review the evidence supporting PET in radiotherapy
      planning, with special emphasis on the role of novel radiopharmaceuticals,
      comparing its sensitivity and specificity with respect to 18F-FDG and other
      anatomic imaging modalities. 

PMID- 24725131
TI  - 18FDG-PET/CT in traumatic brain injury patients: the relative hypermetabolism of
      vermis cerebelli as a medium and long term predictor of outcome.
AB  - PURPOSE: Both, the constant presence of apparent hypermetabolism of the vermis
      cerebelli compared to the cerebellar hemispheres in traumatic brain injury, and
      the presence of a good relationship between the intensity of this sign and the
      severity of the clinical conditions have been addressed in previous studies. Aim
      of the present paper is to evaluate the possible correlation between the
      intensity of the finding and the medium and long term outcome in a group of
      patients. MATERIALS AND METHODS: A group of 105 patients consecutively admitted
      to the Brain Injury Rehabilitation Center of our Hospital between 2005 and 2012
      was studied with a 18FDG-PET/CT study of the brain after head trauma; the
      metabolic activity of the cerebellar vermis was semiquantitatively assessed
      (vermis/cerebellum ratio, V/C). After that, all patients received systematic
      monitoring of their performance status via the timely administration of commonly
      used tests (DRS, LCF and GOS) during one whole year after the head trauma. The
      V/C parameter was compared with the evolution of performance abilities, as shown
      by the rating scales. RESULTS: Statistical analysis showed a significant direct
      association between the V/C ratio and the DRS score at each time point (3 months:
      P<0.001; 6 months: P<0.001; 12 months: P<0.001) and significant inverse
      association with the LCF score (3 months: P<0.001; 6 months: P<0.001; 12 months:
      P<0.001) and the GOS score (3 months: P<0.001; 6 months: P<0.001; 12 months:
      P<0.001) at each time point. Moreover, patients with a V/C ratio >= 1 have a
      significantly greater probability to achieve a good functional outcome as defined
      by a DRS score >= 3 points, a LCF score >= 7 points and and a GOS score =5
      points. CONCLUSIONS: In our group of patients, the V/C parameter has demonstrated
      to be a predictor of outcome. If validated by more extensive experiences, this
      approach could offer the possibility of performing a reliable prognostic
      evaluation in a notoriously "difficult" class of patients with an acceptable
      technique and economical effort.

PMID- 24725132
TI  - Delta-ALA-D inhibitory potential and protective action of Syzygium jambos and
      Solanum guaraniticum leaf extracts on oxidatively stressed erythrocytes.
AB  - OBJECTIVE: This study aimed to investigate the effect of the leaf extracts of
      Syzygium jambos and Solanum guaraniticum on the delta-aminolevulinate dehydratase
      (delta-ALA-D) activity, their antioxidant activity and potential protective
      action on oxidatively stressed erythrocytes, in order to demonstrate the safety
      or toxicity of the plant. METHODS: In erythrocyte samples, the effect of both
      extracts on delta-ALA-D activity, H2O2-induced oxidative stress, and 2,2'azobis
      (2-amidinopropane) (AAPH)-induced hemolysis was evaluated, as well as some
      antioxidant mechanisms. RESULTS: Both extracts inhibited delta-ALA-D activity (S.
      guaraniticum > S. jambos), and an involvement of the zinc ion of the delta-ALA-D
      structure on the inhibition of enzyme activity was verified. S. jambos leaf
      extract showed marked efficiency in countering H2O2-induced lipid peroxidation
      and in maintaining cellular integrity against AAPH-induced hemolysis.
      Furthermore, S. jambos exhibited greater H2O2 scavenging activity and stronger
      reduction power than S. guaraniticum. DISCUSSION: Both extracts bear potent
      antioxidant property as an important beneficial effect. However, the inhibition
      of delta-ALA-D activity suggests a possible harmful effect of these vegetal
      preparations and indicates the need for further investigation regarding their
      toxicological properties. All together, these data represent a significant
      contribution to the knowledge of these plants, both to the scientific community
      and to the folk medicine.

PMID- 24725133
TI  - Time course of neuroprotection induced by normobaric hyperoxia and NCX1
      expression.
AB  - BACKGROUND: The purpose of this study was to determine if normobaric hyperoxia
      (HO) pre-conditioning offers durable neuroprotection against cerebral ischaemia
      and its effects on NCX1 expression. METHODS: Rats were divided into two
      experimental groups. The first group was exposed to 95% inspired HO for 4
      hours/day for 6 consecutive days (HO). The second group acted as control and was
      exposed to 21% oxygen in the same chamber. Each main group was sub-divided to
      middle cerebral artery occlusion (MCAO-operated) and intact (without any surgery)
      sub-groups. After 2, 5, 10 and 15 days from pre-treatment, MCAO-operated sub
      groups were subjected to 60 minutes of right MCAO. After 24 hours reperfusion,
      neurologic deficit score and infarct volume were measured in MCAO-operated sub
      groups. The NCX1 expression levels of core, penumbra and sub-cortex regions were
      assessed in sham-operated and intact sub-groups. RESULTS: Pre-conditioning with
      HO decreased neurologic deficit score and infarct volume, and increased
      expression of NCX1 in penumbra and sub-cortex. These effects of hyperoxia
      disappeared gradually during 15 days after pre-treatment. CONCLUSIONS: Although
      further studies are needed to clarify the mechanisms of time course of
      neuroprotection, HO partly is associated with expression of NCX1 consistent with
      an active role in the genesis of ischaemic neuroprotection.

PMID- 24725135
TI  - High-resolution droplet-based fractionation of nano-LC separations onto
      microarrays for MALDI-MS analysis.
AB  - We present a robust droplet-based device, which enables the fractionation of
      ultralow flow rate nanoflow liquid chromatography (nano-LC) eluate streams at
      high frequencies and high peak resolution. This is achieved by directly
      interfacing the separation column to a micro T-junction, where the eluate stream
      is compartmentalized into picoliter droplets. This immediate compartmentalization
      prevents peak dispersion during eluate transport and conserves the
      chromatographic performance. Subsequently, nanoliter eluate fractions are
      collected at a rate of one fraction per second on a high-density microarray to
      retain the separation with high temporal resolution. Chromatographic separations
      of up to 45 min runtime can thus be archived on a single microarray possessing
      2700 sample spots. The performance of this device is demonstrated by
      fractionating the separation of a tryptic digest of a known protein mixture onto
      the microarray chip and subsequently analyzing the sample archive using matrix
      assisted laser desorption/ionization mass spectrometry (MALDI-MS). Resulting peak
      widths are found to be significantly reduced compared to standard continuous flow
      spotting technologies as well as in comparison to a conventional nano-LC
      electrospray ionization-mass spectrometry interface. Moreover, we demonstrate the
      advantage of our high-definition nanofractionation device by applying two
      different MALDI matrices to all collected fractions in an alternating fashion.
      Since the information that is obtained from a MALDI-MS measurement depends on the
      choice of MALDI matrix, we can extract complementary information from neighboring
      spots containing almost identical composition but different matrices. 

PMID- 24725136
TI  - Effect of the neuropeptides vasoactive intestinal peptide, peptide histidine
      methionine and substance P on human major salivary gland secretion.
AB  - OBJECTIVE: The parasympathetic transmitters vasoactive intestinal peptide (VIP)
      and substance P (SP) are secretagogues in salivary glands of animals. Currently,
      we hypothesise that in human salivary glands, these neuropeptides and the VIP
      related peptide histidine methionine (PHM) also exert secretory actions,
      reflected morphologically by exocytosis of acinar protein/glycoprotein-storing
      granules. MATERIALS AND METHODS: Submandibular and parotid gland tissues, exposed
      in vitro to VIP and PHM, and SP, respectively, were examined by light and
      transmission electron microscopy. For comparison, the response to in vitro
      stimulation of isoproterenol, phenylephrine and carbachol was examined. Moreover,
      the peptidergic innervation of the glands was examined by immunohistochemistry.
      RESULTS: Vasoactive intestinal peptide- and PHM-immunoreactive nerves were in
      close proximity to acini and ducts in the two glands, while these elements lacked
      a SP-positive innervation. While no morphological changes occurred in response to
      SP (parotid glands), VIP and PHM administration (submandibular glands) caused
      conspicuous acinar degranulation accompanied by luminal space broadening. In the
      two glands, both alpha1 - and beta-adrenergic receptor stimulation and muscarinic
      receptor stimulation caused similar changes as to VIP/PHM, although to varying
      extent. CONCLUSIONS: Vasoactive intestinal peptide and PHM, but not SP, are
      likely transmitters in the parasympathetic control of salivary (protein)
      secretion in humans.

PMID- 24725137
TI  - Atomic mechanism of dynamic electrochemical lithiation processes of MoS2
      nanosheets.
AB  - Layered molybdenum disulfide (MoS2) has been studied for decades for its
      diversity of structure and properties, where the structural dynamic evolution
      during lithium intercalation is an important but still indistinct, controversial
      topic. Here the electrochemical dynamic process of MoS2 nanosheets upon lithium
      intercalation has been systematically investigated by in situ high-resolution
      transmission electron microscopy. The results indicate that the lithiated MoS2
      undergoes a trigonal prismatic (2H)-octahedral (1T) phase transition with a
      lithium ion occupying the interlayer S-S tetrahedron site in the 1T-LiMoS2. A
      pseudoperiodic structural modulation composed of polytype superlattices is also
      revealed as a consequence of the electron-lattice interaction. Furthermore, the
      shear mechanism of the 2H-1T phase transition has been confirmed by probing the
      dynamic phase boundary movement. The in situ real-time characterization at atomic
      scale provides a great leap forward in the fundamental understanding of the
      lithium ion storage mechanism in MoS2, which should be also of help for other
      transition metal dichalcogenides. 

PMID- 24725138
TI  - Caesarean section unmasking perivascular epithelioid cell tumour of the uterus.

PMID- 24725139
TI  - Independent contribution of bronchoalveolar lavage and serum galactomannan in the
      diagnosis of invasive pulmonary aspergillosis.
AB  - The optimal combination of galactomannan index (GMI) testing for the diagnosis of
      invasive pulmonary aspergillosis (IPA) remains unclear. For diagnostic approaches
      that are triggered by clinical signs and symptoms in high-risk patients,
      institutional variation remains, with some centers routinely relying on only
      serum GMI or bronchoalveolar lavage (BAL) GMI testing. In addition, use of mold
      active agents before diagnosis of IPA is becoming increasingly common, and
      understanding the effect of these drugs on test yield is important when making
      time-critical treatment decisions. In a single-center cohort of 210 allogeneic
      hematopoietic cell transplant recipients, we found that serum and BAL GMI testing
      contributed independently to IPA diagnosis, supporting the practice of sending
      both tests simultaneously to ensure a timely diagnosis of IPA. BAL GMI
      sensitivity was not affected by receipt of mold-active therapy in our cohort. 

PMID- 24725140
TI  - Fluorescence imaging of human cells with a novel conjugate of the antifungal
      nystatin.
AB  - The antitumor activity of antibacterial and antifungal compounds has been of
      interest in the past. In several investigations glycopeptide antibiotics like
      bleomycin and antifungal agents like itraconazole have shown direct positive
      results whereas antifungal polyenes such as amphotericin B have been shown to
      potentiate the effects of antitumor agents. After having investigated the
      fluorescence-marked antibacterial glycopeptides vancomycin and ramoplanin on
      various malignant and healthy human cells in previous studies, the present work
      is focused on the antifungal polyene nystatin. We coupled nystatin to the
      fluorescent dye fluorescein isothiocyanate (FITC). After confirming the correct
      mass by mass spectrometry the effect of the conjugate on nine different human
      cell lines (two benign and seven tumor cell lines) was examined. The character of
      the uptake was determined by confocal laser scanning microscopy (CLSM) and the
      uptake was quantified by fluorescence activated cell sorting (FACS). The addition
      of propidium iodide (PI) allowed for detection and quantification of cell
      membrane disruption caused by the fluorescein-nystatin conjugate. Uptake of the
      conjugate was found to vary among the nine cell lines investigated. Conjugate
      uptake was strongest after 6 hours in most cell lines. Only the two prostate
      carcinoma cell lines PC3 and LNCaP showed further increase in uptake after long
      time (24h) incubation. PI staining in general correlated well with the conjugate
      FITC staining values. The Colo205 colon carcinoma cell line and the U373 and LN18
      glioblastoma cell lines exhibited very low conjugate uptake and PI staining. The
      results indicate that this conjugate shows potential for future imaging studies
      on certain human cancer cells. 

PMID- 24725141
TI  - The cognitive profile of occipital lobe epilepsy and the selective association of
      left temporal lobe hypometabolism with verbal memory impairment.
AB  - We investigated the cognitive profile of structural occipital lobe epilepsy (OLE)
      and whether verbal memory impairment is selectively associated with left temporal
      lobe hypometabolism on [18F]-fluorodeoxyglucose positron emission tomography (FDG
      PET). Nine patients with OLE, ages 8-29 years, completed presurgical
      neuropsychological assessment. Composite measures were calculated for
      intelligence quotient (IQ), speed, attention, verbal memory, nonverbal memory,
      and executive functioning. In addition, the Wisconsin Card Sorting Test (WCST)
      was used as a specific measure of frontal lobe functioning. Presurgical FDG-PET
      was analyzed with statistical parametric mapping in 8 patients relative to 16
      healthy volunteers. Mild impairments were evident for IQ, speed, attention, and
      executive functioning. Four patients demonstrated moderate or severe verbal
      memory impairment. Temporal lobe hypometabolism was found in seven of eight
      patients. Poorer verbal memory was associated with left temporal lobe
      hypometabolism (p = 0.002), which was stronger (p = 0.03 and p = 0.005,
      respectively) than the association of left temporal lobe hypometabolism with
      executive functioning or with performance on the WCST. OLE is associated with
      widespread cognitive comorbidity, suggesting cortical dysfunction beyond the
      occipital lobe. Verbal memory impairment is selectively associated with left
      temporal lobe hypometabolism in OLE, supporting a link between neuropsychological
      dysfunction and remote hypometabolism in focal epilepsy.

PMID- 24725142
TI  - In vitro multiwavelength PDT with 3IL states: teaching old molecules new tricks.
AB  - The purpose of the present investigation was to ascertain whether (3)IL excited
      states with microsecond lifetimes are universally potent for photodynamic
      applications, and if these long-lived states are superior to their (3)MLCT
      counterparts as in vitro PDT agents. A family of blue-green absorbing, Ru(II)
      based transition metal complexes derived from the pi-expansive dppn ligand was
      prepared and characterized according to its photodynamic activity against HL-60
      cells, and toward DNA in cell-free media. Complexes in this series that are
      characterized by low-energy and long-lived (3)IL excited states photocleaved DNA
      with blue, green, red, and near-IR light. This panchromatic photodynamic effect
      translated to in vitro multiwavelength photodynamic therapy (PDT) with red-light
      cytotoxicities as low as 1.5 MUM (EC50) for the parent complex and 400 nM for its
      more lipophilic counterpart. This potency is similar to that achieved with Ru(II)
      based dyads containing long-lived (3)IL excitons located on appended pyrenyl
      units, and appears to be a general property of sufficiently long-lived excited
      states. Moreover, the red PDT observed for certain members of this family was
      almost 5 times more potent than Photofrin with therapeutic indices 30 times
      greater. Related Ru(II) complexes having lowest-lying (3)MLCT states of much
      shorter duration (<=1 MUs) did not yield DNA photodamage or in vitro PDT with red
      or near-IR light, nor did the corresponding Os(II) complex with a submicrosecond
      (3)IL excited state lifetime. Therefore, metal complexes that utilize highly
      photosensitizing (3)IL excited states, with suitably long lifetimes (? 1 MUs),
      are well-poised to elicit PDT at wavelengths even where their molar extinction
      coefficients are very low (<100 M(-1) cm(-1)). Herein we demonstrate that such
      unexpected reactivity gives rise to very effective PDT in the typical therapeutic
      window (600-850 nm). 

PMID- 24725143
TI  - Observing phthalate leaching from plasticized polymer films at the molecular
      level.
AB  - Phthalates, the most widely used plasticizers in poly(vinyl chloride) (PVC), have
      been extensively studied. In this paper, a highly sensitive, easy, and effective
      method was developed to examine short-term phthalate leaching from PVC/phthalate
      films at the molecular level using sum frequency generation vibrational
      spectroscopy (SFG). Combining SFG and Fourier transform infrared spectroscopy
      (FTIR), surface and bulk molecular structures of PVC/phthalate films were also
      comprehensively evaluated during the phthalate leaching process under various
      environments. The leaching processes of two phthalates, diethyl phthalate (DEP)
      and dibutyl phthalate (DBP), from the PVC/phthalate films with various weight
      ratios were studied. Oxygen plasma was applied to treat the PVC/phthalate film
      surfaces to verify its efficacy on preventing/reducing phthalate leaching from
      PVC. Our results show that DBP is more stable than DEP in PVC/phthalate films.
      Even so, DBP molecules were still found to very slowly leach to the environment
      from PVC at 30  degrees C, at a rate much slower than DEP. Also, the bulk DBP
      content substantially influences the DBP leaching. Higher DBP bulk concentration
      yields less stable DBP molecules in the PVC matrix, allowing molecules to leach
      from the polymer film more easily. Additionally, DBP leaching is very sensitive
      to temperature changes; higher temperature can strongly enhance the leaching
      process. For most cases, the oxygen plasma treatment can effectively prevent
      phthalate leaching from PVC films (e.g., for samples with low bulk concentrations
      of DBP-5 and 30 wt %). It is also capable of reducing phthalate leaching from
      high DBP bulk concentration PVC samples (e.g., 70 wt % DBP in PVC/DBP mixture).
      This research develops a highly sensitive method to detect chemicals at the
      molecular level as well as provides surface and bulk molecular structural
      changes. The method developed here is general and can be applied to detect small
      amounts of chemical/biological environmental contaminants. 

PMID- 24725144
TI  - Systemic corticosteroids for subcutaneous panniculitis-like T-cell lymphoma.
AB  - BACKGROUND: Primary cutaneous gamma/delta T-cell lymphoma (PCGD-TCL) is
      aggressive and has a poor prognosis. In contrast, subcutaneous panniculitis-like
      T-cell lymphoma (SPTCL) of the alpha/beta T-cell receptor phenotype is known to
      follow an indolent course and have a more favourable prognosis. In the past, PCGD
      TCL and SPTCL were often considered to be a manifestation of the same disease,
      and aggressive systemic polychemotherapy has commonly been the first-line therapy
      for both. Given the understanding that SPTCL is a separate and less aggressive
      entity, clinical data exclusively evaluating the efficacy of conservative
      treatment in SPTCL are needed. OBJECTIVES: To assess the overall clinical
      response to systemic corticosteroids in the treatment of SPTCL. METHODS: This was
      a retrospective cross-sectional study based on a patient data repository from two
      tertiary care university hospitals in Zurich (Switzerland) and Tubingen
      (Germany). The repository spanned 13 years. RESULTS: In four of the five patients
      (80%) with SPTCL, treatment with systemic corticosteroids induced a complete
      remission. CONCLUSIONS: Systemic corticosteroids may be an excellent first-line
      single-agent therapy for SPTCL.

PMID- 24725145
TI  - Bioaccessibility and content of Se in fish and shellfish widely consumed in
      Mediterranean countries: influence of proteins, fat and heavy metals.
AB  - Twenty samples of fish and seafood products were selected for determination of
      total and bioaccessible Se (i.e. soluble and dialyzable). The Se contents ranged
      between 0.638-0.052 ug/g. The samples of fatty fish such as mackerel and tuna
      showed higher contents than the species of lean fish, and mainly the fresh water
      fish, such as salmon, trout and panga showed the lowest contents. The fraction of
      soluble Se ranged between 43-84% while that the fraction of dialyzable Se did not
      exceed 14%. No statistically significant correlation was observed between protein
      content and total and bioaccessible Se content. In contrast, a negative
      interaction was observed between bioaccessible Se and fat content, and between
      bioaccessible Se and presence of heavy metals like Cd.

PMID- 24725148
TI  - Obesity and the nutrition transition in Sub-Saharan Africa.
AB  - This review illustrates the outcomes of the nutrition transition in Sub-Saharan
      Africa (SSA) and its association with overweight and obesity; the relationship
      with the double burden of malnutrition is also explored. We describe the increase
      in overweight in nearly all Sub-Saharan African countries and present data on
      associated increased gross domestic product, and availability of energy, protein,
      fat, and sugar at country national levels. Predictors of overweight are described
      by means of various studies undertaken in SSA, and dietary intakes of numerous
      countries are presented. Overall, we show that socioeconomic status, gender, age,
      parity, physical inactivity, and increased energy, fat, and sugar intake are
      powerful predictors of overweight and/or obesity. The urgency for health
      interventions in countries in the early stages of the nutrition transition is
      emphasized, particularly in view of the fact that fat intake is still less than
      30% of energy intake in nearly all Sub-Saharan African countries. 

PMID- 24725149
TI  - The artificial pancreas: current status and future prospects in the management of
      diabetes.
AB  - Recent advances in insulins, insulin pumps, continuous glucose-monitoring
      systems, and control algorithms have resulted in an acceleration of progress in
      the development of artificial pancreas devices. This review discusses progress in
      the development of external systems that are based on subcutaneous drug delivery
      and subcutaneous continuous glucose monitoring. There are two major system-level
      approaches to achieving closed-loop control of blood glucose in diabetic
      individuals. The unihormonal approach uses insulin to reduce blood glucose and
      relies on complex safety mitigation algorithms to reduce the risk of
      hypoglycemia. The bihormonal approach uses both insulin to lower blood glucose
      and glucagon to raise blood glucose, and also relies on complex algorithms to
      provide for safety of the user. There are several major strategies for the design
      of control algorithms and supervision control for application to the artificial
      pancreas: proportional-integral-derivative, model predictive control, fuzzy
      logic, and safety supervision designs. Advances in artificial pancreas research
      in the first decade of this century were based on the ongoing computer revolution
      and miniaturization of electronic technology. The advent of modern smartphones
      has created the ability to utilize smartphone technology as the engineering
      centerpiece of an artificial pancreas. With these advances, an artificial or
      bionic pancreas is within reach. 

PMID- 24725151
TI  - Pd-catalyzed oxidative annulation of hydrazides with isocyanides: synthesis of 2
      amino-1,3,4-oxadiazoles.
AB  - An efficient palladium-catalyzed oxidative annulation reaction was developed
      through sequential isocyanide insertions into N-H and O-H bonds of hydrazides,
      which provides an efficient access to valuable 2-amino-1,3,4-oxadiazoles and
      their derivatives. 

PMID- 24725147
TI  - Obesity and cancer pathogenesis.
AB  - Overweight and obesity have reached pandemic levels on a worldwide basis and are
      associated with increased risk and worse prognosis for many but not all
      malignancies. Pathophysiologic processes that affect this association are
      reviewed, with a focus on the relationship between type 2 diabetes mellitus and
      cancer, lessons learned from the use of murine models to study the association,
      the impact of obesity on pancreatic cancer, the effects of dietary fats and
      cholesterol on cancer promotion, and the mechanisms by which the intestinal
      microbiome affects obesity and cancer. 

PMID- 24725152
TI  - The evolution of selfing from outcrossing ancestors in Brassicaceae: what have we
      learned from variation at the S-locus?
AB  - Evolutionary transitions between mating systems have occurred repetitively and
      independently in flowering plants. One of the most spectacular advances of the
      recent empirical literature in the field was the discovery of the underlying
      genetic machinery, which provides the opportunity to retrospectively document the
      scenario of the outcrossing to selfing transitions in a phylogenetic perspective.
      In this review, we explore the literature describing patterns of polymorphism and
      molecular evolution of the locus controlling self-incompatibility (S-locus) in
      selfing species of the Brassicaceae family in order to document the transition
      from outcrossing to selfing, a retrospective approach that we describe as the
      'mating system genes approach'. The data point to strikingly contrasted scenarios
      of transition from outcrossing to selfing. We also perform original analyses of
      the fully sequenced genomes of four species showing self-compatibility, to
      compare the orthologous S-locus region with that of functional S-locus
      haplotypes. Phylogenetic analyses suggest that all species we investigated
      evolved independently towards loss of self-incompatibility, and in most cases
      almost intact sequences of either of the two S-locus genes suggest that these
      transitions occurred relatively recently. The S-locus region in Aethionema
      arabicum, representing the most basal lineage of Brassicaceae, showed unusual
      patterns so that our analysis could not determine whether self-incompatibility
      was lost secondarily, or evolved in the core Brassicaceae after the split with
      this basal lineage. Although the approach we detail can only be used when mating
      system genes have been identified in a clade, we suggest that its integration
      with phylogenetic and population genetic approaches should help determine the
      main routes of this predominant mating system shift in plants. 

PMID- 24725153
TI  - Requirements of older adults for a daily use of an internet-based cognitive
      training platform.
AB  - A decline of cognitive abilities is a part of normal human ageing. However,
      recent research has demonstrated that an enriched environment can have a
      beneficial impact on cognitive function in old age. Accordingly, mentally and
      socially active lifestyles are associated with less cognitive decline in old age.
      Specific interventions such as computerized cognitive training programs for older
      adults are also known to have a positive effect on the level of cognitive
      functioning. Therefore, online platforms combining cognitive training with web
      2.0 features may yield multiple benefits for older users. However, to date only
      little research exists on technological acceptance and media use in this age
      group especially for cognitively-impaired seniors. Therefore, in order to assess
      specific preferences and potential barriers of older adults regarding a web-based
      platform for cognitive training, we conducted qualitative interviews with 12
      older adults. Half of the participants were diagnosed with mild cognitive
      impairment (MCI). Most importantly, our results show that cognitive exercises
      should incorporate themes and topics older adults are interested in. Additional
      communication features could serve as ideal methods for increasing user
      motivation. Furthermore, we derived eight critical requirements of older adults
      concerning daily use of a web-based cognitive training platform. Implications for
      future research and development are discussed. 

PMID- 24725155
TI  - One-dimensional titanium dioxide nanomaterials: nanowires, nanorods, and
      nanobelts.

PMID- 24725154
TI  - Therapeutic efficacy of the combination of doxorubicin-loaded liposomes with
      inertial cavitation generated by confocal ultrasound in AT2 Dunning rat tumour
      model.
AB  - The combination of liposomal doxorubicin (DXR) and confocal ultrasound (US) was
      investigated for the enhancement of drug delivery in a rat tumour model. The
      liposomes, based on the unsaturated phospholipid dierucoylphosphocholine, were
      designed to be stable during blood circulation in order to maximize accumulation
      in tumour tissue and to release drug content upon US stimulation. A confocal US
      setup was developed for delivering inertial cavitation to tumours in a well
      controlled and reproducible manner. In vitro studies confirm drug release from
      liposomes as a function of inertial cavitation dose, while in vivo
      pharmacokinetic studies show long blood circulation times and peak tumour
      accumulation at 24-48 h post intravenous administration. Animals injected 6 mg
      kg(-1) liposomal DXR exposed to US treatment 48 h after administration show
      significant tumour growth delay compared to control groups. A liposomal DXR dose
      of 3 mg kg(-1), however, did not induce any significant therapeutic response.
      This study demonstrates that inertial cavitation can be generated in such a
      fashion as to disrupt drug carrying liposomes which have accumulated in the
      tumour, and thereby increase therapeutic effect with a minimum direct effect on
      the tissue. Such an approach is an important step towards a therapeutic
      application of cavitation-induced drug delivery and reduced chemotherapy
      toxicity.

PMID- 24725156
TI  - Charge clamps of lysines and hydrogen bonds play key roles in the mechanism to
      fix helix 12 in the agonist and antagonist positions of estrogen receptor alpha:
      intramolecular interactions studied by the ab initio fragment molecular orbital
      method.
AB  - The mechanism to fix helix 12 (H12) in the agonist/antagonist position, which is
      involved in controlling transcriptional activation, of the human estrogen
      receptor alpha ligand binding domain (hERalphaLBD) is studied by using fragment
      molecular orbital calculations at the Moller-Plesset second-order perturbation
      levels to analyze inter-fragment interaction energies (IFIEs), electrostatic
      potentials (ESPs), and atomic charges. The mutually attractive and complementary
      relationships between H12 and highly conserved Lys529/Lys362 are shown through
      the IFIEs and ESPs. The highly conserved Lys529 and Lys362 are found to have
      strong attractive interactions with the anionic residues of H12 in the agonist
      and antagonist positions, respectively, thus playing roles of charge clamps to
      fix H12. Additionally, intramolecular interactions between the neutral residues
      of H12 including the LXXML motif and the other part of hERalpha are strengthened
      by the hydrogen bonds and polarization. It is noted that the highly conserved
      Asp351 forms a hydrogen bond with Leu540 of H12 in the hERalpha-agonist complex,
      while it is also involved in stabilization of ligand binding in the hERalpha
      antagonist complex. The charges of residues at the interface between H12 and the
      other part of hERalpha approach approximately neutral upon forming the
      agonist/antagonist binding conformation so as to relax the electrostatic
      repulsion caused by the negative charges of H12 and the other part of hERalpha.
      Our observations would thus provide useful information to control the H12
      position for regulation of transcription in hERalpha and other nuclear receptors.

PMID- 24725157
TI  - Modulation of cerebral blood flow with transcutaneous electrical neurostimulation
      (TENS) in patients with cerebral vasospasm after subarachnoid hemorrhage.
AB  - OBJECTIVES: Transcutaneous electrical neurostimulation (TENS) and spinal cord
      stimulation have been shown to increase peripheral and cerebral blood flow. We
      postulate that certain pathological conditions attenuate cerebral autoregulation,
      which may result in a relative increase of the importance of neurogenic
      regulation of cerebral blood flow, which could be decreased by electrical
      modulation. We therefore assess the effects of TENS on cerebral blood flow
      velocities (CBFVs) and cerebral saturation in patients with cerebral vasospasm
      after subarachnoid hemorrhage (SAH). MATERIALS AND METHODS: Cervical TENS was
      applied in 10 SAH patients with transcranial Doppler (TCD)-proven cerebral
      vasospasm. Measurements included plethysmography, near-infrared spectroscopy,
      capnography, and CBFVs by TCD. After determining the optimal frequency and
      current, patients were treated with cervical TENS for two periods of three days,
      with a pause of one day in between. RESULTS: The TENS electrodes were not always
      tolerated by the patients. Higher frequencies demonstrated the most prominent
      combined effects. ETCO2 was 0.19% lower with TENS off than with TENS on (p =
      0.05). Mean arterial blood pressure and pulse were not significantly different
      over time. CBFV in MCA was decreased (p = 0.07) while cerebral oxygen saturation
      was increased (p = 0.01) after the use of TENS. CONCLUSIONS: Our data suggest
      improved cerebral blood flow when using cervical TENS in patients with cerebral
      vasospasm. Several factors could have attenuated the effects: the electrodes were
      poorly tolerated, ETCO2 increased during TENS, few vessels showed prolonged
      vasospasm, and overall flow velocities were low. Still, an on-off effect of TENS
      over time was detected.

PMID- 24725158
TI  - Solid-phase synthesis of anagrelide sulfonyl analogues.
AB  - Simple solid-phase synthesis of 3,10-dihydro-2H-benzo[e]imidazo[1,2
      b][1,2,4]thiadiazin-2-one 5,5-dioxides is described, with Fmoc-alpha-amino acids
      and 2-nitrobenzenesulfonyl chlorides (2-NosCls) being the key building blocks.
      Fmoc-alpha-amino acids were immobilized on Wang resin and transformed to the
      corresponding 2-nitrobenzenesulfonamides in two steps. After reduction of the
      nitro group, Fmoc-thioureas were synthesized followed by cyclization of the 1,2,4
      benzothiadiazine-1,1-dioxide scaffold with diisopropylcarbodiimide (DIC).
      Cleavage of the Fmoc protecting group followed by spontaneous cyclative cleavage
      gave the target products in excellent crude purity. 

PMID- 24725159
TI  - Cytotoxic constituents from Lobaria scrobiculata and a comparison of two
      bioassays for their evaluation.
AB  - Lichens are resilient organisms, known for their unique profiles of secondary
      metabolites and for exhibiting antioxidative, antibacterial, and cytotoxic
      effects. Analyzing the cytotoxic potential of Lobaria scrobiculata, a bioassay
      guided fractionation strategy yielded seven known metabolites, with two of these
      compounds, 2 and 3, exhibiting cytotoxicity against HL-60 cells. In order to
      verify the potential impact of degradation on observed bioactivity, a purity and
      stability evaluation was conducted. The consistency of results obtained by the
      water-soluble tetrazolium salt-1 assay and trypan blue cytotoxicity assay was
      evaluated for selected compounds. 

PMID- 24725160
TI  - Veterinary treatment and rehabilitation of indigenous wildlife.
AB  - Veterinary surgeons in general practice are frequently presented with injured or
      orphaned animals by wildlife rescue centres, members of the public or police
      officers. Following treatment, many of these animals are released to the wild.
      Despite the large numbers of wildlife casualties rehabilitated in this way there
      are few published data detailing species, numbers treated, quality of care
      provided and outcome following release. There is also ongoing debate regarding
      the welfare and conservation benefits of such human intervention. This article
      reviews the available published evidence on wildlife rehabilitation and offers
      recommendations on future policy. 

PMID- 24725161
TI  - Rapid isolation of high solute amounts using an online four-dimensional
      preparative system: normal phase-liquid chromatography coupled to methyl siloxane
      ionic liquid-wax phase gas chromatography.
AB  - This study reports the recent evolution of a multidimensional GC-GC-GC
      preparative system, now combined with an online LC preseparation step, operated
      under normal phase conditions. It is herein shown that the four-dimensional
      instrument can collect sample components with a concentration lower than 10%, in
      a short time period, while maintaining a high level of analyte purity. The LC
      dimension allows (I) the injection of higher sample amounts, compared to "direct"
      GC injection; (II) a polarity-based preseparation, leading to the GC injection of
      simplified subsamples, and thus reducing the possibility of coelutions; (III) to
      eliminate the essential-oil "matrix", replacing it with the LC mobile phase (the
      GC system is more protected from potential contamination); (IV) the LC mobile
      phase is of much lower viscosity with respect to a pure, or highly concentrated
      essential oil, avoiding difficulties in the syringe sample withdrawal process,
      prior to GC injection. System optimization was performed by using standard
      solutions; in addition, a very complex sample, namely, vetiver essential oil, was
      subjected to the preparative process, with the scope of isolating two low-amount
      constituents (namely, alpha-amorphene and beta-vetivone). The latter two
      sesquiterpenoids, which accounted for 1.7 and 4.0% of the sample (considering the
      volatiles), respectively, were successfully collected at the milligram level, in
      a one-day work period, with a purity degree in excess of 90%. 

PMID- 24725162
TI  - Psychometric qualities of a tetrad WAIS-III short form for use in individuals
      with mild to borderline intellectual disability.
AB  - OBJECTIVE: To investigate the reliability and validity of a Wechsler Abbreviated
      Scale of Intelligence-based Wechsler Adult Intelligence Scale - third edition
      (WAIS-III) short form (SF) in a sample of individuals with mild to borderline
      intellectual disability (MBID) (N = 117; M(IQ) = 71.34; SD(IQ) = 8.00, range: 52
      85). METHODS: A full WAIS-III was administered as a standard procedure in the
      diagnostic process. RESULTS: The results indicate an excellent reliability (r =
      0.96) and a strong, positive correlation with the full WAIS-III (r = 0.89). The
      SF correctly identified ID in general and the correct IQ category more
      specifically in the majority of cases (97.4% and 86.3% of cases, respectively).
      In addition, 82.1% of the full scale IQ (FSIQ) estimates fell within the 95%
      confidence interval of the original score. CONCLUSIONS: We conclude that the SF
      is a reliable and valid measure to estimate FSIQ. It can be used in clinical and
      research settings when global estimates of intelligence are sufficient.

PMID- 24725163
TI  - Stellatolides, a new cyclodepsipeptide family from the sponge Ecionemia acervus:
      isolation, solid-phase total synthesis, and full structural assignment of
      stellatolide A.
AB  - The marine environment is a rich source of metabolites with potential therapeutic
      properties and applications for humans. Here we describe the first isolation,
      solid-phase total synthesis, and full structural assignment of a new class of
      cyclodepsipeptides from the Madagascan sponge Ecionemia acervus that shows in
      vitro cytotoxic activities at submicromolar concentrations. Seven structures
      belonging to a new family of compounds, given the general name stellatolides,
      were characterized. The sequence and stereochemistry of all the amino acids in
      these molecules were established by a combination of spectroscopic analysis,
      chemical degradation, and derivatization studies. Furthermore, the complete
      structure of stellatolide A was confirmed by an efficient solid-phase method for
      the first total synthesis and the full structural assignment of this molecule,
      including the asymmetric synthesis of the unique beta-hydroxy acid moiety (Z)-3
      hydroxy-6,8-dimethylnon-4-enoic acid. 

PMID- 24725164
TI  - The secret of the care of the patient is in knowing and applying the evidence
      about effective clinical communication.
AB  - American physicians and dentists conduct approximately 140 000-160 000 patient
      interviews in a practice lifetime, making the interview the most frequently
      performed medical procedure. Over the past 75 years, a steadily growing stream of
      scientific research has confirmed the fact that patient-clinician communication
      affects the course, direction, and both biomedical and functional outcomes of
      care. The field of clinical communication research has matured from anecdotes and
      aphorisms about 'bedside manner' to sophisticated randomized control trials and
      evidence-based outcomes that have been translated into reliable practice
      guidelines. Several key skills or habits of practice have been identified and
      studied in terms of their efficacy and effectiveness. These include the
      importance of agenda-setting, eliciting patients' perspectives about the nature
      of their ailments, communicating caring and concern, and testing for patient
      comprehension and agreement with proposed treatments. In addition to being
      effective, interpersonal communication can be deeply satisfying as well as
      offering a lower probability of law suits in the event of an adverse outcome.

PMID- 24725165
TI  - An unusual ovarian cyst.

PMID- 24725167
TI  - Control of corona composition and morphology in aggregates of mixtures of PS-b
      PAA and PS-b-P4VP diblock copolymers: effects of pH and block length.
AB  - The corona compositions and morphologies in aggregates of mixtures of amphiphilic
      polystyrene-block-poly(acrylic acid) (PS-b-PAA) and polystyrene-block-poly(4
      vinylpyridine) (PS-b-P4VP) diblock copolymers are influenced by controllable
      assembly parameters such as the hydrophilic block length and solution pH. The
      morphologies and corona compositions of the aggregates were investigated by
      transmission electron microscopy and electrophoretic mobility, respectively. When
      mineral acids or bases are present during aggregate formation, they can exert a
      strong influence on the corona composition. Morphology changes were also seen
      with changing pH, as well as changes in corona composition, specifically for
      vesicles. Because of complications introduced by the presence of ions, the
      general hypothesis that the external corona of the vesicles is composed of the
      longer chains, while the shorter chains form the inner corona, which is valid
      only in mixtures containing only nonionic chains without any additives (no acids
      or bases) or within a well-defined narrow pH range. In addition to the numerical
      block lengths and the pH, the solubility of the hydrophilic blocks can also
      influence the morphology and as well as the interfacial composition of vesicles;
      as the numerically longer chains become less soluble, they can contract and move
      to the interior, while the numerically shorter but more soluble chains go to the
      external corona. A remarkable morphological feature of the pH continuum is that
      for some compositions vesicles are observed in four distinct pH regions,
      separated by pH ranges in which other morphologies dominate. The effect of pH and
      microion content on coil dimensions of the PVP and PAA chains in the block
      copolymers is most likely responsible for the observed behavior. 

PMID- 24725166
TI  - Association of obesity and treated hypertension and diabetes with cognitive
      ability in bipolar disorder and schizophrenia.
AB  - OBJECTIVES: People with bipolar disorder or schizophrenia are at greater risk for
      obesity and other cardio-metabolic risk factors, and several prior studies have
      linked these risk factors to poorer cognitive ability. In a large ethnically
      homogenous outpatient sample, we examined associations among variables related to
      obesity, treated hypertension and/or diabetes and cognitive abilities in these
      two patient populations. METHODS: In a study cohort of outpatients with either
      bipolar disorder (n = 341) or schizophrenia (n = 417), we investigated the
      association of self-reported body mass index and current use of medications for
      hypertension or diabetes with performance on a comprehensive neurocognitive
      battery. We examined sociodemographic and clinical factors as potential
      covariates. RESULTS: Patients with bipolar disorder were less likely to be
      overweight or obese than patients with schizophrenia, and also less likely to be
      prescribed medication for hypertension or diabetes. However, obesity and treated
      hypertension were associated with worse global cognitive ability in bipolar
      disorder (as well as with poorer performance on individual tests of processing
      speed, reasoning/problem-solving, and sustained attention), with no such
      relationships observed in schizophrenia. Obesity was not associated with symptom
      severity in either group. CONCLUSIONS: Although less prevalent in bipolar
      disorder compared to schizophrenia, obesity was associated with substantially
      worse cognitive performance in bipolar disorder. This association was independent
      of symptom severity and not present in schizophrenia. Better understanding of the
      mechanisms and management of obesity may aid in efforts to preserve cognitive
      health in bipolar disorder.

PMID- 24725169
TI  - Efficacy and tolerability of tamsulosin 0.4 mg in Asian patients with lower
      urinary tract symptoms secondary to benign prostatic hyperplasia refractory to
      tamsulosin 0.2 mg: a randomized placebo controlled trial.
AB  - OBJECTIVES: To evaluate the efficacy and safety of tamsulosin dose increase to
      0.4 mg daily in Asian patients with lower urinary tract symptoms secondary to
      benign prostatic hyperplasia refractory to tamsulosin 0.2 mg treatment. METHODS:
      We carried out a 12-week, single-center, randomized, placebo-controlled trial in
      220 patients. Patients treated with 0.2 mg tamsulosin daily without other lower
      urinary tract symptoms secondary to benign prostatic hyperplasia medication for
      more than 3 months and refractory to this treatment were enrolled. We defined
      "refractory" as an International Prostate Symptom Score of 13 or greater and a
      maximum flow rate of 15 or under despite medication. Patients with a surgical
      history related to lower urinary tract symptoms secondary to benign prostatic
      hyperplasia or a postvoid residual of 150 mL or greater were excluded. Eligible
      patients were randomly assigned to the 0.4 mg group (two tablets of 0.2 mg
      tamsulosin once daily) or the 0.2 mg group (one tablet of 0.2 mg tamsulosin and
      one tablet of placebo once daily). International Prostate Symptom Score, maximum
      flow rate, blood pressure, heart rate, and adverse events were compared between
      the two groups at 4 weeks and 12 weeks. RESULTS: A total of 220 patients were
      enrolled and analyzed. There were no differences in baseline characteristics
      between the two groups. After 12 weeks of medication, the International Prostate
      Symptom Score was not different between the two groups. However, the improvement
      in maximum flow rate was greater in the 0.4 mg group than the 0.2 mg group (3.0
      +/- 0.48 mL/s vs -0.25 +/- 0.30 mL/s, P < 0.01). The proportion of patients who
      showed an increase in maximum flow rate of more than 5 mL/s was 10.9% in the 0.2
      mg group versus 16.3% in the 0.4 mg group (P = 0.209). There were no significant
      differences in bother score or postvoid residual between the two groups. Systolic
      and diastolic blood pressure, and heart rate were also not different between the
      two groups. The incidence of adverse events was 10.9% in the 0.2 mg group
      (dizziness 5.5%; abnormal ejaculation 1.8%; palpitation 1.8%; and headache 1.8%)
      and 9.09% in the 0.4 mg group (dizziness 3.6%; abnormal ejaculation 1.8%;
      palpitations 1.8%; and headache 1.8%). CONCLUSIONS: Tamsulosin 0.4 mg appears to
      be a safe treatment regimen for treating lower urinary tract symptoms secondary
      to benign prostatic hyperplasia in Asian patients who do not respond to 0.2 mg
      treatment. Increasing the dose of tamsulosin results in a significant improvement
      in maximum flow rate without any increase in cardiovascular complications.

PMID- 24725170
TI  - Recognizing odd smells and ejection of brood parasitic eggs. An experimental test
      in magpies of a novel defensive trait against brood parasitism.
AB  - One of the most important defensive host traits against brood parasitism is the
      detection and ejection of parasitic eggs from their nests. Here, we explore the
      possible role of olfaction in this defensive behaviour. We performed egg
      recognition tests in magpie Pica pica nests with model eggs resembling those of
      parasitic great spotted cuckoos Clamator glandarius. In one of the experiment,
      experimental model eggs were exposed to strong or moderate smell of tobacco
      smoke, whereas those of a third group (control) were cleaned with disinfecting
      wipes and kept in boxes containing odourless cotton. Results showed that model
      eggs with strong tobacco scent were more frequently ejected compared with control
      ones. In another experiment, models were smeared with scents from cloacal wash
      from magpies (control), cloacal wash or uropygial secretions from cuckoos, or
      human scents. This experiment resulted in a statistically significant effect of
      treatment in unparasitized magpie nests in which control model eggs handled by
      humans were more often rejected. These results provide the first evidence that
      hosts of brood parasites use their olfactory ability to detect and eject foreign
      eggs from their nests. These findings may have important consequences for
      handling procedures of experimental eggs used in egg-recognition tests, in
      addition to our understanding of interactions between brood parasites and their
      hosts. 

PMID- 24725171
TI  - A one-pot allylation-hydrostannation sequence with recycling of the intermediate
      tin waste.
AB  - A one-pot allylation and hydrostannation of alkynals where the tin byproduct
      formed in the first step of the reaction is recycled and used in the second step
      of the sequence is presented. Specifically, a BF3.OEt2-promoted allylstannation
      of the aldehyde moiety in the alkynal is followed by the introduction of
      polymethylhydrosiloxane (PMHS) and catalytic B(C6F5)3, which convert the tin
      byproduct of the allylation into Bu3SnH, which then hydrostannates the alkyne in
      the molecule. (119)Sn and (11)B NMR data suggest an organotin fluoride species is
      formed during the allylation step and involved in the tin recycling step. 

PMID- 24725172
TI  - Comparative study of time-dependent effects of 4 and 8 Hz mechanical vibration at
      infrasound frequency on E. coli K-12 cells proliferation.
AB  - The aim of the present work is to study the time-dependent effects of mechanical
      vibration (MV) at infrasound (IS) frequency at 4 and 8 Hz on E. coli K-12 growth
      by investigating the cell proliferation, using radioactive [(3)H]-thymidine
      assay. In our previous work it was suggested that the aqua medium can serve as a
      target through which the biological effect of MV on microbes could be realized.
      At the same time it was shown that microbes have mechanosensors on the surface of
      the cells and can sense small changes of the external environment. The obtained
      results were shown that the time-dependent effects of MV at 4 and 8 Hz frequency
      could either stimulate or inhibit the growth of microbes depending from exposure
      time. It more particularly, the invention relates to a method for controlling
      biological functions through the application of mechanical vibration, thus making
      it possible to artificially control the functions of bacterial cells, which will
      allow us to develop method that can be used in agriculture, industry, medicine,
      biotechnology to control microbial growth. 

PMID- 24725173
TI  - Effect of pomegranate peel supplementation on nutritional, organoleptic and
      stability properties of cookies.
AB  - The present study aims at highlighting the nutritive potential of pomegranate
      peel and its possible utilization as an ingredient of choice to nutritionally
      enrich cookies. Biochemical composition and free radical scavenging features of
      pomegranate peel powder (PoP) and PoP supplemented cookies were measured. PoP
      supplementation significantly (p < 0.05) improved dietary fibers (0.32-1.96 g/100
      g), total phenols (90.7-161.9 mg GAE/100 g) and inorganic residues (0.53-0.76
      g/100 g) of cookies. Similarly, significant increase in Ca, K, Fe and Zn levels
      was noted in supplemented cookies. Almost 50% 2,2-diphenyl-1-picrylhydrazyl
      (DPPH) radical scavenging activity was recorded in cookies carrying highest
      concentration of PoP and phenolic contents. PoP phenolics of supplemented cookies
      were shown to reduce oxidative degradation during four months storage. Present
      study suggests PoP supplementation in baked products as a potential source of
      micro and macronutrients. Application of PoP in ready to serve foods seems to be
      a potential disease preventive and ameliorative approach in tandem with its
      preservation and nutritional enhancement features.

PMID- 24725174
TI  - Expression dynamics of CXCL12 and CXCR4 during the progression of mycosis
      fungoides.
AB  - BACKGROUND: Mycosis fungoides (MF) classically presents from patch stage to
      plaque stage over a number of years and finally progresses to tumour stage with
      nodal or visceral involvement. The mechanism of progression remains incompletely
      elucidated. Chemokines and their receptors are known to be involved in disease
      mechanisms, with CXCL12 and CXCR4 playing a critical role in carcinogenesis,
      invasion and cancer cell migration in various carcinomas. OBJECTIVES: To
      investigate the expression of CXCL12 and CXCR4 in different cutaneous stages of
      MF. METHODS: Formalin-fixed, paraffin-embedded skin samples from 40 patients with
      MF (21 patch stage, 10 plaque stage, nine tumour stage) and 30 non-neoplastic
      control skin samples were analysed. CXCL12 and CXCR4 were assessed by
      quantitative reverse-transcription polymerase chain reaction and
      immunohistochemical staining. RESULTS: The expression level of mRNA for CXCL12 in
      plaque-stage MF was significantly higher than in control skin (P = 0.0035), or
      patch-stage (P = 0.0108) or tumour-stage disease (P = 0.0089). The CXCR4 mRNA
      expression level in plaque-stage disease was significantly higher than in control
      skin (P = 0.0090) or patch-stage disease (P = 0.0387). CXCL12- and CXCR4-positive
      cell rates in patch-stage and plaque-stage MF were significantly higher than
      those in control skin (P < 0.0001). CXCL12- and CXCR4-positive cell rates in
      tumour-stage MF were significantly lower than those in patch- and plaque-stage
      disease (P = 0.0274 and P = 0.0492, respectively). CONCLUSIONS: Our data suggest
      that neoplastic T cells in MF are exposed to the microenvironment, given the
      abundance of CXCL12 during its progression, and also that neoplastic T cells
      express CXCR4, especially in the pretumour stage. We reveal that the CXCL12-CXCR4
      axis plays a critical role in MF progression.

PMID- 24725176
TI  - Exploring free-energy landscapes of intrinsically disordered proteins at atomic
      resolution using NMR spectroscopy.

PMID- 24725175
TI  - Job strain and the risk of severe asthma exacerbations: a meta-analysis of
      individual-participant data from 100 000 European men and women.
AB  - BACKGROUND: Many patients and healthcare professionals believe that work-related
      psychosocial stress, such as job strain, can make asthma worse, but this is not
      corroborated by empirical evidence. We investigated the associations between job
      strain and the incidence of severe asthma exacerbations in working-age European
      men and women. METHODS: We analysed individual-level data, collected between 1985
      and 2010, from 102 175 working-age men and women in 11 prospective European
      studies. Job strain (a combination of high demands and low control at work) was
      self-reported at baseline. Incident severe asthma exacerbations were ascertained
      from national hospitalization and death registries. Associations between job
      strain and asthma exacerbations were modelled using Cox regression and the study
      specific findings combined using random-effects meta-analyses. RESULTS: During a
      median follow-up of 10 years, 1 109 individuals experienced a severe asthma
      exacerbation (430 with asthma as the primary diagnostic code). In the age- and
      sex-adjusted analyses, job strain was associated with an increased risk of severe
      asthma exacerbations defined using the primary diagnostic code (hazard ratio, HR:
      1.27, 95% confidence interval, CI: 1.00, 1.61). This association attenuated
      towards the null after adjustment for potential confounders (HR: 1.22, 95% CI:
      0.96, 1.55). No association was observed in the analyses with asthma defined
      using any diagnostic code (HR: 1.01, 95% CI: 0.86, 1.19). CONCLUSIONS: Our
      findings suggest that job strain is probably not an important risk factor for
      severe asthma exacerbations leading to hospitalization or death.

PMID- 24725177
TI  - Characterization of the immersion properties of the peripheral membrane anchor of
      the FATC domain of the kinase "target of rapamycin" by NMR, oriented CD
      spectroscopy, and MD simulations.
AB  - The multidomain ser/thr kinase "target of rapamycin" (TOR) centrally controls
      eukaryotic growth and metabolism. The C-terminal FATC domain is important for TOR
      regulation and was suggested to directly mediate TOR-membrane interactions. Here,
      we present a detailed characterization of the membrane immersion properties of
      the oxidized and reduced yeast TOR1 FATC domain (2438-2470 = y1fatc). The
      immersion depth was characterized by NMR-monitored interaction studies with DPC
      micelles containing paramagnetically tagged 5- or 16-doxyl stearic acid (5-/16
      SASL) and by analyzing the paramagnetic relaxation enhancement (PRE) from Mn(2+)
      in the solvent. Complementary MD-simulations of micellar systems in the absence
      and presence of protein showed that 5-/16-SASL can move in the micelle and that
      16-SASL can bend such that the doxyl group is close to the headgroup region and
      not deep in the interior as commonly assumed. Based on oriented CD (OCD) data,
      the single alpha-helix of oxidized/reduced y1fatc has an angle to the membrane
      normal of ~30-60 degrees /~35-65 degrees  in neutral and ~5-35 degrees /~0-30
      degrees  in negatively charged bilayers. The presented experimentally well
      founded models help to better understand how this redox-sensitive peripheral
      membrane anchor may be part of a network of protein-protein and protein-membrane
      interactions regulating TOR localization at different cellular membranes.
      Moreover, the presented work provides a good methodological reference for the
      structural characterization of other peripherally membrane associating proteins.

PMID- 24725178
TI  - Editorial: readmission.

PMID- 24725179
TI  - Intradural tumor recurrence after resection of extradural metastasis: a rare but
      potential complication of intraoperative durotomy.
AB  - Spinal metastases are the most common of spinal neoplasms and occur predominantly
      in an extradural location. Their appearance in an intradural location is uncommon
      and is associated with a poor prognosis. Cerebrospinal fluid dissemination
      accounts for a significant number of intradural spinal metastases mostly
      manifesting as leptomeningeal carcinomatoses or drop metastases from intracranial
      tumors. The occurrence of local tumor dissemination intradurally following
      surgery for an extradural spinal metastasis has not been reported previously. The
      authors describe 2 cases in which local intradural and intramedullary tumor
      recurrences occurred following resection of extradural metastases that were
      complicated by unintended durotomy. To heighten clinical awareness of this
      unusual form of local tumor recurrence, the authors discuss the possible etiology
      and clinical consequences of this entity. 

PMID- 24725180
TI  - Safety and accuracy of robot-assisted versus fluoroscopy-guided pedicle screw
      insertion for degenerative diseases of the lumbar spine: a matched cohort
      comparison.
AB  - OBJECT: Recent years have been marked by efforts to improve the quality and
      safety of pedicle screw placement in spinal instrumentation. The aim of the
      present study is to compare the accuracy of the SpineAssist robot system with
      conventional fluoroscopy-guided pedicle screw placement. METHODS: Ninety-five
      patients suffering from degenerative disease and requiring elective lumbar
      instrumentation were included in the study. The robot cohort (Group I; 55
      patients, 244 screws) consisted of an initial open robot-assisted subgroup
      (Subgroup IA; 17 patients, 83 screws) and a percutaneous cohort (Subgroup IB, 38
      patients, 161 screws). In these groups, pedicle screws were placed under robotic
      guidance and lateral fluoroscopic control. In the fluoroscopy-guided cohort
      (Group II; 40 patients, 163 screws) screws were inserted using anatomical
      landmarks and lateral fluoroscopic guidance. The primary outcome measure was
      accuracy of screw placement on the Gertzbein-Robbins scale (Grade A to E and R
      [revised]). Secondary parameters were duration of surgery, blood loss, cumulative
      morphine, and length of stay. RESULTS: In the robot group (Group I), a perfect
      trajectory (A) was observed in 204 screws (83.6%). The remaining screws were
      graded B (n = 19 [7.8%]), C (n = 9 [3.7%]), D (n = 4 [1.6%]), E (n = 2 [0.8%]),
      and R (n = 6 [2.5%]). In the fluoroscopy-guided group (Group II), a completely
      intrapedicular course graded A was found in 79.8% (n = 130). The remaining screws
      were graded B (n = 12 [7.4%]), C (n = 10 [6.1%]), D (n = 6 [3.7%]), and E (n = 5
      [3.1%]). The comparison of "clinically acceptable" (that is, A and B screws) was
      neither different between groups (I vs II [p = 0.19]) nor subgroups (Subgroup IA
      vs IB [p = 0.81]; Subgroup IA vs Group II [p = 0.53]; Subgroup IB vs Group II [p
      = 0.20]). Blood loss was lower in the robot-assisted group than in the
      fluoroscopy-guided group, while duration of surgery, length of stay, and
      cumulative morphine dose were not statistically different. CONCLUSIONS: Robot
      guided pedicle screw placement is a safe and useful tool for assisting spine
      surgeons in degenerative spine cases. Nonetheless, technical difficulties remain
      and fluoroscopy backup is advocated.

PMID- 24725181
TI  - Fracture of the L-4 vertebral body after use of a stand-alone interbody fusion
      device in degenerative spondylolisthesis for anterior L3-4 fixation.
AB  - Many studies attest to the excellent results achieved using anterior lumbar
      interbody fusion (ALIF) for degenerative spondylolisthesis. The purpose of this
      report is to document a rare instance of L-4 vertebral body fracture following
      use of a stand-alone interbody fusion device for L3-4 ALIF. The patient, a 55
      year-old man, had suffered intractable pain of the back, right buttock, and left
      leg for several weeks. Initial radiographs showed Grade I degenerative
      spondylolisthesis, with instability in the sagittal plane (upon 15 degrees 
      rotation) and stenosis of central and both lateral recesses at the L3-4 level.
      Anterior lumbar interbody fusion of the affected vertebrae was subsequently
      conducted using a stand-alone cage/plate system. Postoperatively, the severity of
      spondylolisthesis diminished, with resolution of symptoms. However, the patient
      returned 2 months later with both leg weakness and back pain. Plain radiographs
      and CT indicated device failure due to anterior fracture of the L-4 vertebral
      body, and the spondylolisthesis had recurred. At this point, bilateral
      facetectomies were performed, with reduction/fixation of L3-4 by pedicle screws.
      Again, degenerative spondylolisthesis improved postsurgically and symptoms eased,
      with eventual healing of the vertebral body fracture. This report documents a
      rare instance of L-4 vertebral body fracture following use of a stand-alone
      device for ALIF at L3-4, likely as a consequence of angular instability in
      degenerative spondylolisthesis. Under such conditions, additional pedicle screw
      fixation is advised. 

PMID- 24725182
TI  - High incidence of morbidity following resection of metastatic pheochromocytoma in
      the spine.
AB  - Pheochromocytomas of the spine are uncommon and require careful preoperative
      planning. The authors retrospectively reviewed the charts of 5 patients with
      metastatic spinal pheochromocytoma who had undergone surgical treatment over the
      past 10 years at their medical center. They reviewed patient age, history of
      pheochromocytoma resection, extent and location of metastases, history of alpha
      blockage, surgical level, surgical procedure, postoperative complications, tumor
      recurrence, and survival. Metastases involved the cervical (1 patient), thoracic
      (3 patients), and lumbar (2 patients) levels. Preoperative treatment included
      primary pheochromocytoma resection, chemotherapy, alpha blockade, embolization,
      and radiation. Three patients had tumor recurrence, and 2 underwent 2-stage
      reoperations for tumor extension. Hemodynamic complications were common: 2
      patients developed pulseless electrical activity arrest within 4 months after
      surgery, 1 patient had profound postoperative tachycardia with fever and an
      elevated creatine kinase level, and 1 patient experienced transient postoperative
      hypotension and paraplegia. One patient died of complications related to
      disseminated cerebral and spinal disease. With careful preoperative and surgical
      management, patients with symptomatic metastatic spinal pheochromocytoma can
      benefit from aggressive surgical treatment. Postoperative cardiovascular
      complications are common even months after surgery, and patients should be
      closely monitored long term. 

PMID- 24725183
TI  - Predictors of unplanned readmission in patients undergoing lumbar decompression:
      multi-institutional analysis of 7016 patients.
AB  - OBJECT: Unplanned hospital readmission represents a large financial burden on the
      Centers for Medicare and Medicaid Services, commercial insurance payers,
      hospitals, and individual patients, and is a principal target for cost reduction.
      A large-scale, multi-institutional study that evaluates risk factors for
      readmission has not been previously performed in patients undergoing lumbar
      decompression procedures. The goal of this multicenter retrospective study was to
      find preoperative, intraoperative, and postoperative predictive factors that
      result in unplanned readmission (UR) after lumbar decompression surgery. METHODS:
      The National Surgical Quality Improvement Program (NSQIP) database was
      retrospectively reviewed to identify all patients who received lumbar
      decompression procedures in 2011. Risk-adjusted multivariate logistic regression
      analysis was performed to estimate independent predictors of UR. RESULTS: The
      overall rate of UR among patients undergoing lumbar decompression was 4.4%. After
      multivariate logistic regression analysis, anemia (odds ratio [OR] 1.48),
      dependent functional status (OR 3.03), total operative duration (OR 1.003), and
      American Society of Anesthesiologists Physical Status Class 4 (OR 3.61) remained
      as independent predictors of UR. Postoperative complications that were
      significantly associated with UR included overall complications (OR 5.18),
      pulmonary embolism (OR 3.72), and unplanned reoperation (OR 56.91). CONCLUSIONS:
      There were several risk factors for UR after lumbar spine decompression surgery.
      Identification of high-risk patients and appropriate allocation of resources to
      reduce postoperative incidence may reduce the readmission rate.

PMID- 24725184
TI  - De novo designed library of linear helical peptides: an exploratory tool in the
      discovery of protein-protein interaction modulators.
AB  - Protein-protein interactions (PPIs) have emerged as important targets for
      pharmaceutical intervention because of their essential role in numerous
      physiological and pathological processes, but screening efforts using small
      molecules have led to very low hit rates. Linear peptides could represent a quick
      and effective approach to discover initial PPI hits, particularly if they have
      inherent ability to adopt specific peptide secondary structures. Here, we address
      this hypothesis through a linear helical peptide library, composed of four
      sublibraries, which was designed by theoretical predictions of helicity (Agadir
      software). The 13-mer peptides of this collection fixes either a combination of
      three aromatic or two aromatic and one aliphatic residues on one face of the
      helix (Ac-SSEEX(5)ARNX(9)AAX(12)N-NH2), since these are structural features quite
      common at PPIs interfaces. The 81 designed peptides were conveniently synthesized
      by parallel solid-phase methodologies, and the tendency of some representative
      library components to adopt the intended secondary structure was corroborated
      through CD and NMR experiments. As proof of concept in the search for PPI
      modulators, the usefulness of this library was verified on the widely studied p53
      MDM2 interaction and on the communication between VEGF and its receptor Flt-1,
      two PPIs for which a hydrophobic alpha-helix is essential for the interaction. We
      have demonstrated here that, in both cases, selected peptides from the library,
      containing the right hydrophobic sequence of the hot-spot in one of the protein
      partners, are able to interact with the complementary protein. Moreover, we have
      discover some new, quite potent inhibitors of the VEGF-Flt-1 interaction, just by
      replacing one of the aromatic residues of the initial F(5)Y(9)Y(12) peptide by W,
      in agreement with previous results on related antiangiogenic peptides. Finally,
      the HTS evaluation of the full collection on thermoTRPs has led to a few
      antagonists of TRPV1 and TRPA1 channels, which open new avenues on the way to
      innovative modulators of these channels. 

PMID- 24725185
TI  - Radiographic and MRI characteristics of lumbar disseminated idiopathic spinal
      hyperostosis and spondylosis deformans in dogs.
AB  - OBJECTIVES: To evaluate clinical signs, describe lesions and differences in the
      magnetic resonance imaging appearance of spinal new bone formations classified as
      disseminated idiopathic spinal hyperostosis and/or spondylosis deformans on
      radiographs and compare degeneration status of the intervertebral discs using the
      Pfirrmann scale. METHODS: Retrospective analysis of 18 dogs presented with spinal
      disorders using information from radiographic and magnetic resonance imaging
      examinations. RESULTS: All dogs were found to be affected with both disseminated
      idiopathic spinal hyperostosis and spondylosis deformans. Neurological signs due
      to foraminal stenosis associated with disseminated idiopathic spinal hyperostosis
      were found in two dogs. Spondylosis deformans was associated with foraminal
      stenosis and/or disc protrusion in 15 cases. The Pfirrmann score on magnetic
      resonance imaging was significantly higher in spondylosis deformans compared with
      disseminated idiopathic spinal hyperostosis and signal intensity of new bone due
      to disseminated idiopathic spinal hyperostosis was significantly higher compared
      to spondylosis deformans. CLINICAL SIGNIFICANCE: Differences between disseminated
      idiopathic spinal hyperostosis and spondylosis deformans found on magnetic
      resonance imaging contribute to an increased differentiation between the two
      entities. Clinically relevant lesions in association with disseminated idiopathic
      spinal hyperostosis were rare compared to those seen with spondylosis deformans.

PMID- 24725186
TI  - Definitive chemoradiation for patients with inoperable and/or unresectable
      esophageal cancer: locoregional recurrence pattern.
AB  - A locoregional recurrence after definitive chemoradiation (dCRT) for patients
      with inoperable or unresectable esophageal cancer occurs in about 50% of the
      patients and is a major cause of failure with a poor prognosis. The aim of this
      study was to determine the pattern of locoregional recurrence and its prognostic
      factors after dCRT in order to search for improvements in radiation treatment. We
      retrospectively reviewed 184 patients treated with external beam radiotherapy
      (50.4 Gray/28 fractions), combined with weekly concurrent paclitaxel and
      carboplatin. Locoregional recurrences were defined by clinical signs of recurrent
      or progressive disease, combined with progression on computed tomography/positron
      emission tomography-computed tomography scan, or suspicious endoscopic findings
      and/or histological proof of recurrence. The site of locoregional recurrence was
      analyzed with respect to the borders of the radiation fields. After a mean follow
      up of 22.8 months, 76 patients (41%) had evidence of locoregional recurrence. The
      3-years locoregional recurrence-free rate was 45%. The majority of locoregional
      recurrences occurred within 12 months, nearly all within 24 months. The majority
      of these patients failed at the site of the primary tumor (86%). Infield
      locoregional recurrences at the site of the lymph nodes only occurred in 1%
      compared with 57% at the site of the primary tumor only. Outfield locoregional
      lymph node recurrences occurred in 22%, without infield recurrence occurred in
      only 4% of all patients. The 1-, 3-, and 5-year overall survival was 65%, 28%,
      and 21%, respectively. The current analysis demonstrates that a locoregional
      recurrence after dCRT occurs in 41% of the patients, the majority at the site of
      the primary tumor. These data suggest a benefit of dose intensification of the
      primary tumor, but not at the site of the lymph nodes. Higher radiation doses
      should be assessed with prospective trials. 

PMID- 24725187
TI  - Arginine-derived advanced glycation end products generated in peptide-glucose
      mixtures during boiling.
AB  - Glycation refers to the reaction of amino groups, for example in proteins, with
      reducing sugars. Intermediately formed Amadori products can be degraded by
      oxidation (Maillard reactions) leading to a heterogeneous class of advanced
      glycation end-products (AGEs), especially during exposure to heat. AGEs are
      considered to be toxic in vivo due to their pronounced local and systemic
      inflammatory effects. At high temperatures, these reactions have been mostly
      investigated at the amino acid level. Here, we studied the formation of arginine
      related AGEs in peptides under conditions simulating household cooking at
      physiological d-glucose concentrations. High quantities of AGE-modified peptides
      were produced within 15 min, especially glyoxal-derived products. The
      intermediately formed dihydroxy-imidazolidine yielded glyoxal- (Glarg) and
      methylglyoxal-derived hydro-imidazolinones (MG-H), with Glarg being further
      degraded to carboxymethyl-l-arginine (CMA). Carboxyethyl-l-arginine was not
      detected. The formation rates and yields were strongly increased in the presence
      of physiologically relevant concentrations of Fe(II)-ions and ascorbate. A nearby
      histidine residue increased the content of AGEs, whereas glutamic acid
      significantly reduced the CMA levels. 

PMID- 24725188
TI  - The identification and biochemical properties of the catalytic specificity of a
      serine peptidase secreted by Aspergillus fumigatus Fresenius.
AB  - Aspergillus fumigatus is a saprophytic fungus as well as a so-called opportunist
      pathogen. Its biochemical potential and enzyme production justify intensive
      studies about biomolecules secreted by this microorganism. We describe the
      alkaline serine peptidase production, with optimum activity at 50 degrees C and a
      pH of 7.5 and a reduction in proteolytic activity in the presence of the Al(+3)
      ions. When using intramolecularly quenched fluorogenic substrates, the highest
      catalytic efficiency was observed with the amino acid leucine on subsite S'(3)
      (60,000 mM(-1)s(-1)) and preference to non-polar amino acids on subsite S(3). In
      general, however, the peptidase shows non-specificity on other subsites studied.
      According to the biochemical characteristics, this peptidase may be an important
      biocatalyst for the hydrolysis of an enormous variety of proteins and can
      constitute an essential molecule for the saprophytic lifestyle or invasive action
      of the opportunistic pathogen. The peptidase described herein exhibits an
      estimated molecular mass of 33 kDa. Mass spectrometry analysis identified the
      sequence GAPWGLGSISHK displaying similarities to that of serine peptidase from
      Aspergillus fumigatus. These data may lead to a greater understanding of the
      advantageous biochemical potential, biotechnological interest, and trends of this
      fungus in spite of being an opportunist pathogen. 

PMID- 24725189
TI  - Capillary zone electrophoresis-electrospray ionization-tandem mass spectrometry
      for top-down characterization of the Mycobacterium marinum secretome.
AB  - Capillary zone electrophoresis (CZE) with an electrokinetically pumped sheath
      flow nanospray interface was coupled with a high-resolution Q-Exactive mass
      spectrometer for the analysis of culture filtrates from Mycobacterium marinum. We
      confidently identified 22 gene products from the wildtype M. marinum secretome in
      a single CZE-tandem mass spectrometry (MS/MS) run. A total of 58 proteoforms were
      observed with post-translational modifications including signal peptide removal,
      N-terminal methionine excision, and acetylation. The conductivities of aqueous
      acetic acid and formic acid solutions were measured from 0.1% to 100%
      concentration (v/v). Acetic acid (70%) provided lower conductivity than 0.25%
      formic acid and was evaluated as low ionic-strength and a CZE-MS compatible
      sample buffer with good protein solubility. 

PMID- 24725190
TI  - Delivering quality care: what can emergency gynaecology learn from acute
      obstetrics?
AB  - Emergency obstetric care in the UK has been systematically developed over the
      years to high quality standards. More recently, advances have been made in the
      organisation and delivery of care for women presenting with acute gynaecological
      problems, but a lot remains to be done, and emergency gynaecology has a lot to
      learn from the evolution of its sister special interest area: acute obstetric
      care. This paper highlights areas such as consultant presence, risk management,
      patient flow pathways, out-of-hours care, clinical guidelines and protocols,
      education and training and facilities, where lessons from obstetrics are
      transferrable to emergency gynaecology.

PMID- 24725191
TI  - Formation and electronic structures of organoeuropium sandwich nanowires.
AB  - Organoeuropium sandwich clusters, comprising europium (Eu) and 1,3,5,7
      cyclooctatetraene (COT) (Eu(n)(COT)(m)), were produced in the gas phase using a
      laser vaporization synthesis method. Photoionization mass spectra revealed an
      exclusive Eu(n)(COT)(m) formation with three compositions: m = n + 1, m = n, and
      m = n - 1, which, we propose, correspond to full-sandwich, half-sandwich, and
      inverted-sandwich structures, respectively. The charge distributions, metal
      ligand bonding characteristics, and electronic structures of the clusters were
      comprehensively investigated by photoionization measurements of Eu(n)(COT)(m)
      neutrals and by photoelectron spectroscopy of Eu(n)(COT)(m)(-) and isoelectronic
      Ba(n)(COT)(m)(-) anions. The results confirmed that (1) highly ionic metal-ligand
      bonding is formed between Eu(2+) and COT(2-) within the sandwich structure (at
      the termini, ionic forms are Eu(+) and COT(-)) and (2) size dependence of orbital
      energy can be explained by the Coulombic interaction of simple point charge
      models between the detaching electrons and dipoles/quadrupoles. When the terminus
      of the sandwich clusters is Eu(2+), COT(2-), or Eu(0), the orbital energy of the
      electron detachment channel at the opposite terminus strongly depends on the
      cluster size. In this case, the molecular stack behaves as a one-dimensionally
      aligned dipole; otherwise, it behaves as a quadrupole, and the relationship
      between cluster size and electron detachment energy is much weaker. The study
      also reports on the 4f orbital energy in Eu ions and the formation mechanism of
      organoeuropium sandwich nanowires up to 12 nm in length. The nanowires are formed
      by successive charge transfer at the terminal part, Eu(+) and COT(-), which
      reduces the ionization energy and increases the electron affinity, respectively.

PMID- 24725192
TI  - Heart rate and heart rate variability parameters at rest, during activity and
      passive standing among children with cerebral palsy GMFCS IV-V.
AB  - AIMS: To describe and compare heart rate (HR) and heart rate variability (HRV) at
      rest, during active movements and passive standing among children with cerebral
      palsy (CP), with Gross Motor Function Classification System (GMFCS) levels IV and
      V, and to describe the association between daily physical activity and HRV.
      METHODS: Thirty children with CP were included aged 6-12 years. HR and HRV
      parameters were recorded during rest, during Gross Motor Functional Measure
      (GMFM) assessment, during two minutes of repeated performance of the highest
      activity achieved in the GMFM, and during passive standing. Parents were asked to
      inform about any habitual physical activities their child participates outside
      school in the previous 4 months. RESULTS: Children with GMFCS IV increased their
      HR and reduced HRV values during the GMFM assessment, the repeated task and
      during passive standing, while no such effect was noted among children with GMFCS
      V. Children participated in a limited range of activities with a median frequency
      of three times a week (range 1-6 times), with insignificant differences between
      GMFCS levels. No significant differences were noted in HR or HRV parameters based
      on activity level. CONCLUSIONS: Only children with GMFCS IV responded to passive
      and active manipulation of the cardiac autonomic system. This may imply that the
      HR autonomic regulation system has an opportunity to be influenced by training in
      this group of children.

PMID- 24725193
TI  - Bipolar polygenic loading and bipolar spectrum features in major depressive
      disorder.
AB  - OBJECTIVES: Family and genetic studies indicate overlapping liability for major
      depressive disorder and bipolar disorder. The purpose of the present study was to
      determine whether this shared genetic liability influences clinical presentation.
      METHODS: A polygenic risk score for bipolar disorder, derived from a large genome
      wide association meta-analysis, was generated for each subject of European
      American ancestry (n = 1,274) in the Sequential Treatment Alternatives to Relieve
      Depression study (STAR*D) outpatient major depressive disorder cohort. A
      hypothesis-driven approach was used to test for association between bipolar
      disorder risk score and features of depression associated with bipolar disorder
      in the literature. Follow-up analyses were performed in two additional cohorts.
      RESULTS: A generalized linear mixed model including seven features hypothesized
      to be associated with bipolar spectrum illness was significantly associated with
      bipolar polygenic risk score [F = 2.07, degrees of freedom (df) = 7, p = 0.04].
      Features included early onset, suicide attempt, recurrent depression, atypical
      depression, subclinical mania, subclinical psychosis, and severity. Post-hoc
      univariate analyses demonstrated that the major contributors to this omnibus
      association were onset of illness at age <= 18 years [odds ratio (OR) = 1.2, p =
      0.003], history of suicide attempt (OR = 1.21, p = 0.03), and presence of at
      least one manic symptom (OR = 1.16, p = 0.02). The maximal variance in these
      traits explained by polygenic score ranged from 0.8% to 1.1%. However, analyses
      in two replication cohorts testing a five-feature model did not support this
      association. CONCLUSIONS: Bipolar genetic loading appeared to be associated with
      bipolar-like presentation in major depressive disorder in the primary analysis.
      However, the results were at most inconclusive because of lack of replication.
      Replication efforts were challenged by different ascertainment and assessment
      strategies in the different cohorts. The methodological approach described here
      may prove useful in applying genetic data to clarify psychiatric nosology in
      future studies.

PMID- 24725194
TI  - Clinical characteristics and oncological outcomes of testicular cancer patients
      registered in 2005 and 2008: the first large-scale study from the Cancer
      Registration Committee of the Japanese Urological Association.
AB  - OBJECTIVES: To describe the clinical and pathological characteristics and
      oncological outcomes of testicular cancer diagnosed in Japan, we report the
      results of the testicular cancer registration carried out by the Japanese
      Urological Association. METHODS: Testicular cancer survey was conducted by the
      Japanese Urological Association in 2011 to register newly diagnosed testicular
      cancers in 2005 and 2008. The survey included details such as age, presenting
      symptoms, physical examination findings, tumor markers, histopathology, clinical
      stage, initial treatment and clinical outcomes. RESULTS: We analyzed 1121 cases
      of testicular primary germ cell tumor among 1157 registered patients. The median
      age was 37.0 years. Seminomas and non-seminomatous germ cell tumors accounted for
      61.9% and 38.1%, respectively. Measurements of tumor markers were documented in
      98.6% of the patients; however, there was an unsatisfactory uniform measurement
      of human chorionic gonadotropin, which made it difficult to evaluate the
      International Germ Cell Consensus Classification in all patients. The 1- and 3
      year overall survival rates from the entire cohort were 98.3% and 96.8%,
      respectively. According to the International Germ Cell Consensus Classification,
      3-year overall survival rates in the good, intermediate, and poor prognosis group
      were 99.1%, 100% and 79.9%, respectively. CONCLUSIONS: The present report is the
      first large-scale study of the characteristics and survival of testicular cancer
      patients in Japan based on multi-institutional registry data, and showed a good
      prognosis even in an advanced stage. The improved survival attributed
      substantially to accurate diagnosis and effective multimodal treatment.

PMID- 24725195
TI  - A role for kappa-, but not mu-opioid, receptor activation in acute food
      deprivation-induced reinstatement of heroin seeking in rats.
AB  - Stress is considered to be one of the major triggers to drug relapse, even after
      prolonged periods of abstinence. In rats, the activation of stress-related brain
      systems, including corticotropin-releasing factor and norepinephrine, is critical
      for stress-induced reinstatement of extinguished drug seeking, an animal model
      for drug relapse. In addition, there are strong indications that activation of
      the endogenous opioid system is important for the effects of stress on drug
      seeking. More specifically, activation of the dynorphin/kappa opioid receptor
      (KOR) system is critically involved in the reinstatement of cocaine seeking
      following exposure to stressors, such as footshock, forced swimming or social
      stress. However, studies on the role of the dynorphin/KOR system in stress
      induced reinstatement of heroin seeking are scarce. Here, rats were trained to
      self-administer heroin (0.1 mg/kg/infusion) for 10 days. Drug seeking was then
      extinguished and the rats were tested for acute (21 hours) food deprivation
      induced reinstatement of heroin seeking. In two separate experiments, rats were
      injected with the mu-opioid receptor (MOR) antagonist, naltrexone (0.0, 1.0, 10.0
      mg/kg; s.c.) or the KOR antagonist, norBNI (0.0, 1.0, 10.0 mg/kg; i.p.) before
      the reinstatement test. Naltrexone treatment did not affect stress-induced
      reinstatement. In contrast, treatment with norBNI dose-dependently attenuated
      food deprivation-induced reinstatement of heroin seeking. These results support
      the hypothesis that activation of KOR, but not MOR, is critically involved in
      stress-induced reinstatement of drug seeking. 

PMID- 24725196
TI  - Synthetic strategy toward the C44-C65 fragment of mirabalin.
AB  - A convergent and flexible stereoselective synthesis of one isomer of the C44-C65
      fragment of mirabalin is described. The key steps include organocatalytic
      aldolization, ruthenium-catalyzed asymmetric hydrogenation, amide formation,
      Marshall stereoselective allenylation, and the Nozaki-Hiyama-Kishi reaction. 

PMID- 24725198
TI  - Cardiometabolic outcomes in children and adolescents following discontinuation of
      long-term risperidone treatment.
AB  - OBJECTIVE: Second-generation antipsychotics (SGAs) cause weight gain and
      cardiometabolic abnormalities in children and adolescents. Less well-investigated
      is the outcome of these adverse events following SGA discontinuation, which we
      examined. METHODS: Medically healthy 7 to 17-year-old patients treated with
      risperidone for >=6 months were enrolled and returned for follow-up, 1.5 years
      later. Treatment history was extracted from the medical and pharmacy records.
      Anthropometric and laboratory measurements were obtained at each research visit.
      Multivariable linear regression analysis and Fisher's exact test were used to
      compare participants who remained on risperidone at follow-up (Risp Cont Group)
      with those who had discontinued SGA treatment (SGA Disc Group) and those who had
      switched to another SGA (SGA Cont Group). Correlational analyses examined the
      association between change in age-sex specific body mass index (BMI) z score
      between study entry and follow-up and change in cardiometabolic outcomes.
      RESULTS: The sample consisted of 101 participants (93% male) with a mean age of
      11.7+/-2.6 years at study entry. The majority had an externalizing disorder and
      received 0.03+/-0.02 mg/kg/day of risperidone, for 2.5+/-1.6 years. At follow-up,
      18% (n=18) were in the SGA Disc Group and 9% (n=9) were in the SGA Cont Group.
      BMI z score decreased in the SGA Disc Group, remained unchanged in the Risp Cont
      Group (n=74), and increased in the SGA Cont Group. Importantly, the change in BMI
      z score between study entry and follow-up was significantly correlated with the
      change in systolic and diastolic blood pressure z scores, heart rate, waist
      circumference, percent body fat, inflammatory markers, fasting total insulin,
      homeostatic model assessment insulin resistance index (HOMA-IR), C-peptide,
      total, low-density lipoprotein (LDL), and high-density lipoprotein (HDL)
      cholesterol, triglycerides, triglycerides/HDL ratio, and leptin. CONCLUSIONS:
      Following several years of treatment, risperidone discontinuation is associated
      with a reversal of the excessive weight gain, mediated by a negative energy
      balance, and a corresponding improvement in cardiometabolic parameters.

PMID- 24725199
TI  - Phonemic verbal fluency is associated with pediatric anxiety disorders: evidence
      from a community study.
AB  - BACKGROUND: Anxiety disorders typically begin in childhood and adolescence and
      predict risk for many problems throughout life. Although some neuropsychological
      correlates have been described, more research is needed, particularly in
      adolescents. This study compares neurocognitive characteristics of anxious
      adolescents with and without comorbidity to externalizing disorders to those of
      typically developing comparison (TDC) adolescents and adolescents with
      externalizing disorders alone. METHODS: The study included 57 adolescents 12-18
      years of age (TDC, n=23; anxiety, n=16; externalizing, n=11; comorbid, n=7). We
      used a neuropsychological battery to assess eight domains: Orientation,
      attention, visual perception, memory, arithmetic, language, praxis, and executive
      function. RESULTS: Multivariate analysis of variance revealed a main effect of
      group in the neurocognitive domains evaluated (F8,48=2.32, p=0.034,
      etap(2)=0.279). Post-hoc analysis revealed that executive functions score
      differed among groups, specifically in the task of verbal fluency (F[df=3]=5.01,
      p=0.004, etap(2)=0.221), with both the anxious groups (anxiety and comorbid)
      presenting a lower score than the TDC and externalizing groups. This effect was
      independent of age, intelligence, and levels of education. CONCLUSIONS: Verbal
      fluency is specifically impaired in adolescents with anxiety disorders. This
      extends results from neuroimaging research implicating prefrontal areas in
      pediatric anxiety disorder neurobiology, and has potential implications to new
      therapeutics.

PMID- 24725200
TI  - Mania in an adolescent with autism and premenstrual mood variation: a diagnostic
      and treatment dilemma.

PMID- 24725201
TI  - Effects of Saccharomyces cerevisiae cell wall extract and poplar propolis ethanol
      extract supplementation on growth performance, digestibility, blood profile,
      fecal microbiota and fecal noxious gas emissions in growing pigs.
AB  - A total of 105 growing pigs (24.91 +/- 1.06 kg) were used in a 6-week trial to
      investigate the effects of including Saccharomyces cerevisiae cell wall extract
      and poplar propolis ethanol extract (SPE) in the diet on growth performance,
      digestibility, blood profiles, fecal microbiota and fecal noxious gas emissions.
      Pigs were randomly allocated to one of three dietary treatments (seven
      pens/treatment, five pigs/pen) according to initial body weight and sex (two
      gilts and three barrows). Treatments consisted of a corn soybean meal basal diet
      supplemented with 0, 0.05 or 0.10% SPE. There was a significant linear
      improvement (P < 0.05) in average daily gain, gain/feed, the apparent total tract
      digestibility of dry matter, nitrogen, and gross energy, blood lymphocyte
      percentage, immunoglobulin G concentration, fecal Escherichia coli and
      Lactobacillus counts as well as fecal NH3 and H2 S emissions associated with the
      inclusion of SPE in the diet. Average daily feed intake, red blood cells and
      white blood cells concentration were not significantly (P > 0.05) affected by SPE
      supplementation in the diets. In conclusion, results indicate that dietary SPE
      supplementation can improve growth performance, digestibility and fecal
      microbiota, and decrease fecal gas emissions in growing pigs. 

PMID- 24725203
TI  - The efficacy and safety of cryoprecipitate in the treatment of acquired
      hypofibrinogenaemia.

PMID- 24725204
TI  - Asthma control assessment in a pediatric population: comparison between
      GINA/NAEPP guidelines, Childhood Asthma Control Test (C-ACT), and physician's
      rating.
AB  - BACKGROUND: Guidelines recommend regular assessment of asthma control. The
      Childhood Asthma Control Test (C-ACT) is a clinically validated tool. AIM: To
      evaluate asthma control according to GINA2006, NAEPP, pediatrician's assessment
      (PA), and C-ACT in asthmatic children visiting their ambulatory pediatrician or
      tertiary care pediatric pulmonologist. METHODS: Demographic data, treatment, and
      number of severe exacerbations during the previous year were collected. Control
      was assessed using (i) strict GINA 2006 criteria, (ii) GINA without taking into
      account the exacerbation item, (iii) NAEPP criteria, and (iv) PA. Children and
      parents filled out the C-ACT. RESULTS: Five hundred and twenty-five children
      completed the survey (mean age: 7.7 years; 28% <= 6 years). 78% had a controller
      treatment. 58% reported >= 1 severe exacerbation. C-ACT was <= 19 in 29.5%.
      Control was not achieved in 76.5%, 55%, 40%, and 34% according to GINA 2006
      guidelines, NAEPP guidelines, GINA 2006 without exacerbation criteria, and PA,
      respectively. C-ACT was significantly lower in children <= 6 years old (P =
      0.002) or with severe exacerbations (P < 0.0001). According to PA, 89% of
      patients with a C-ACT > 21 were controlled and 85% of patients with a C-ACT < 17
      not controlled. CONCLUSION: We observed discrepancies between the different tools
      applied to assess asthma control in children, and the impact of age and
      exacerbations. Cutoff point of 19 of C-ACT was not associated with the best
      performance compared to PA. Assessment of control should take into account
      symptoms and lung function as suggested by the latest GINA guidelines as well as
      exacerbation over a long period.

PMID- 24725205
TI  - Avidity mechanism of dendrimer-folic acid conjugates.
AB  - Multivalent conjugation of folic acid has been employed to target cells
      overexpressing folate receptors. Such polymer conjugates have been previously
      demonstrated to have high avidity to folate binding protein. However, the lack of
      a monovalent folic acid-polymer material has prevented a full binding analysis of
      these conjugates, as multivalent binding mechanisms and polymer-mass mechanisms
      are convoluted in samples with broad distributions of folic acid-to-dendrimer
      ratios. In this work, the synthesis of a monovalent folic acid-dendrimer
      conjugate allowed the elucidation of the mechanism for increased binding between
      the folic acid-polymer conjugate and a folate binding protein surface. The
      increased avidity is due to a folate-keyed interaction between the dendrimer and
      protein surfaces that fits into the general framework of slow-onset, tight
      binding mechanisms of ligand/protein interactions. 

PMID- 24725206
TI  - The endo-arabinanase BcAra1 is a novel host-specific virulence factor of the
      necrotic fungal phytopathogen Botrytis cinerea.
AB  - The plant cell wall is one of the first physical interfaces encountered by plant
      pathogens and consists of polysaccharides, of which arabinan is an important
      constituent. During infection, the necrotrophic plant pathogen Botrytis cinerea
      secretes a cocktail of plant cell-wall-degrading enzymes, including endo
      arabinanase activity, which carries out the breakdown of arabinan. The roles of
      arabinan and endo-arabinanases during microbial infection were thus far elusive.
      In this study, the gene Bcara1 encoding for a novel alpha-1,5-L-endo-arabinanase
      was identified and the heterologously expressed BcAra1 protein was shown to
      hydrolyze linear arabinan with high efficiency whereas little or no activity was
      observed against the other oligo- and polysaccharides tested. The Bcara1 knockout
      mutants displayed reduced arabinanase activity in vitro and severe retardation in
      secondary lesion formation during infection of Arabidopsis leaves. These results
      indicate that BcAra1 is a novel endo-arabinanase and plays an important role
      during the infection of Arabidopsis. Interestingly, the level of Bcara1
      transcript was considerably lower during the infection of Nicotiana benthamiana
      compared with Arabidopsis and, consequently, the DeltaBcara1 mutants showed the
      wild-type level of virulence on N. benthamiana leaves. These results support the
      conclusion that the expression of Bcara1 is host dependent and is a key
      determinant of the disease outcome. 

PMID- 24725207
TI  - Recognition of an Avr3a homologue plays a major role in mediating nonhost
      resistance to Phytophthora capsici in Nicotiana species.
AB  - Nonhost resistance is a commonly occurring phenomenon wherein all accessions or
      cultivars of a plant species are resistant to all strains of a pathogen species
      and is likely the manifestation of multiple molecular mechanisms. Phytophthora
      capsici is a soil-borne oomycete that causes Phytophthora blight disease in many
      solanaceous and cucurbitaceous plants worldwide. Interest in P. capsici has
      increased considerably with the sequencing of its genome and its increasing
      occurrence in multiple crops. However, molecular interactions between P. capsici
      and both its hosts and its nonhosts are poorly defined. We show here that tobacco
      (Nicotiana tabacum) acts like a nonhost for P. capsici and responds to P. capsici
      infection with a hypersensitive response (HR). Furthermore, we have found that a
      P. capsici Avr3a-like gene (PcAvr3a1) encoding a putative RXLR effector protein
      produces a HR upon transient expression in tobacco and several other Nicotiana
      species. This HR response correlated with resistance in 19 of 23 Nicotiana
      species and accessions tested, and knock-down of PcAvr3a1 expression by host
      induced gene silencing allowed infection of resistant tobacco. Our results
      suggest that many Nicotiana species have the capacity to recognize PcAvr3a1 via
      the products of endogenous disease resistance (R) genes and that this R gene
      mediated response is a major component of nonhost resistance to P. capsici. 

PMID- 24725208
TI  - Fermentation in 24-well plates is an efficient screening platform for filamentous
      fungi.
AB  - Fermentation by filamentous fungi in Erlenmeyer flasks is a favoured method for
      comparing different fermentation conditions. However, significant inter-flask
      variation often occurs when using Erlenmeyer flasks, which makes the comparison
      of fermentation product levels less reliable. We have investigated the use of a
      24-well plate method for citric acid, ethanol and glycerol batch fermentation
      using the filamentous fungi Aspergillus carbonarius and compared the relative
      standard deviation (RSD) from sextuplicates obtained using Erlenmeyer flasks and
      24-well plates. The production levels using the Erlenmeyer flasks showed a
      combined average RSD of 29%, which is two and a half-fold higher than what was
      measured using the 24-well plates showing an average RSD of 12%. We conclude that
      fermentation in 24-well plates is a more reliable screening method for metabolite
      production by filamentous fungi and possibly for screening metabolites in
      general. SIGNIFICANCE AND IMPACT OF THE STUDY: Fermentation studies with
      filamentous fungi and especially screening experiments often struggle with high
      inter-vessel variations in metabolite production. This study compares two
      different types of frequently used screening methods namely batch fermentation in
      Erlenmeyer flasks with batch fermentation in 24-well plates. The results
      demonstrate that the variance potentially can be reduced two and a half-fold
      using 24-well plates leading to improved resolution when testing the impact of
      varying fermentation parameters on product formation.

PMID- 24725209
TI  - Postpartum haemorrhage from a large uterus with concealed fibroids.

PMID- 24725210
TI  - Characteristic hydrolyzing of megalosaccharide by human salivary alpha-amylase
      and small intestinal enzymes, and its bioavailability in healthy subjects.
AB  - The digestibility of Megalosaccharide(r) (newly developed carbohydrate comprising
      alpha-1,4-glucosaccharide) was investigated in vitro and in vivo. Isomaltosyl
      megalosaccharide(r) (IMS) and nigerosyl-megalosaccharide(r) (NMS) contain 20% and
      50% of the megalosaccharide fraction (degree of polymerization (DP) 10-35),
      respectively. IMS was hydrolyzed readily by alpha-amylase to oligosaccharides (DP
      <= 7), and a small amount of glucose was produced from oligosaccharides by small
      intestinal enzymes (SIEs). NMS was partially hydrolyzed by alpha-amylase to
      oligosaccharides, and a small amount of glucose produced by SIEs. When IMS and
      NMS were treated by SIEs after treatment with human saliva alpha-amylase for a
      few minutes, IMS and NMS were hydrolyzed readily to glucose. Plasma levels of
      glucose and insulin upon ingestion of 50 g of IMS or NMS were elevated the same
      as those for 50 g of glucose, and breath hydrogen was not excreted. These results
      suggest that IMS and NMS are digestible carbohydrates.

PMID- 24725211
TI  - Erythropoietin protects newborn rat against sevoflurane-induced neurotoxicity.
AB  - INTRODUCTION: Recent data on newborn animals exposed to anesthetics have raised
      safety concerns regarding anesthesia practices in young children. Indeed, studies
      on rodents have demonstrated a widespread increase in brain apoptosis shortly
      after exposure to sevoflurane, followed by long-term neurologic impairment. In
      this context, we aimed to evaluate the protective effect of rh-EPO, a potent
      neuroprotective agent, in rat pups exposed to sevoflurane. MATERIAL AND METHODS:
      At postnatal day 7, 75 rat pups were allocated into three groups: SEVO + EPO (n =
      27) exposed to sevoflurane 2 vol% (0.5 MAC) for 6 h in an air/O2 mixture (60/40)
      + 5000 UI.kg(-1) rh-EPO IP; SEVO (n = 27) exposed to sevoflurane + vehicle IP;
      and CONTROL (n = 21) exposed to the mixture without sevoflurane + vehicle IP.
      Three days after anesthesia (D10), apoptosis was quantified on brain extract with
      TUNEL method and caspase 3. NGF and BDNF expression was determined by Western
      blotting. Rats reaching adulthood were evaluated in terms of exploration
      capacities (object exploration duration) together with spatial and object
      learning (water maze and novel object test). RESULTS: Sevoflurane exposure
      impaired normal behavior in adult rats by reducing the exploratory capacities
      during the novel object test and impaired both spatial and object learning
      capacities in adult rats (water maze, ratio time to find platform 3rd trial/1st
      trial: 1.1 +/- 0.2 vs 0.4 +/- 0.1; n = 9, SEVO vs CONTROL; P = 0.01). Rh-EPO
      reduced sevoflurane-induced behavior and learning abnormalities in adult rats
      (water maze, ratio time to find platform 3rd trial/1st trial: 0.3 +/- 0.1 vs 1.1
      +/- 0.2; n = 9, SEVO + EPO vs SEVO; P = 0.01). Three days after anesthesia, rh
      EPO prevented sevoflurane-induced brain apoptosis (5 +/- 3 vs 35 +/- 6 apoptotic
      cells.mm(-2) ; n = 6, SEVO + EPO vs SEVO; P = 0.01) and elevation of caspase
      three level and significantly increased the brain expression of BDNF and NGF (n =
      6, SEVO + EPO vs SEVO; P = 0.01). CONCLUSION: Six hours of sevoflurane anesthesia
      in newborn rats induces significant long-term cognitive impairment. A single
      administration of rh-EPO immediately after postnatal exposure to sevoflurane
      reduces both early activation of apoptotic phenomenon and late onset of
      neurologic disorders.

PMID- 24725212
TI  - Hydration behavior at the ice-binding surface of the Tenebrio molitor antifreeze
      protein.
AB  - Molecular dynamics (MD) simulations have been carried out at two different
      temperatures (300 and 220 K) to study the conformational rigidity of the
      hyperactive Tenebrio molitor antifreeze protein (TmAFP) in aqueous medium and the
      structural arrangements of water molecules hydrating its surface. It is found
      that irrespective of the temperature the ice-binding surface (IBS) of the protein
      is relatively more rigid than its nonice-binding surface (NIBS). The presence of
      a set of regularly arranged internally bound water molecules is found to play an
      important role in maintaining the flat rigid nature of the IBS. Importantly, the
      calculations reveal that the strategically located hydroxyl oxygens of the
      threonine (Thr) residues in the IBS influence the arrangements of five sets of
      ordered waters around it on two parallel planes that closely resemble the basal
      plane of ice. As a result, these waters can register well with the ice basal
      plane, thereby allowing the IBS to preferentially bind at the ice interface and
      inhibit its growth. This provides a possible molecular reason behind the ice
      binding activity of TmAFP at the basal plane of ice. 

PMID- 24725213
TI  - A retrospective analysis of children with anisometropic amblyopia in Nepal.
AB  - PURPOSE: Anisometropia is one of the main causes of amblyopia. This study was
      conducted to investigate the association between the depth of amblyopia and the
      magnitude of anisometropia. METHODS: A retrospective record review was conducted
      at the Nepal Eye Hospital between July 2006 and June 2011. Those children
      included in this study were aged <=13 years and diagnosed with unilateral
      anisometropic amblyopia, no strabismus and ocular pathology. Associations between
      the depth of amblyopia and the age and/or gender of the subjects, the laterality
      of the amblyopic eyes, the type and magnitude of refractive error of amblyopic
      eyes, and the magnitude of anisometropia were statistically analyzed. RESULTS:
      Out of the 189 children with unilateral anisometropic amblyopia (mean age 9.1 +/-
      2.8 years), 59% were boys. Amblyopia was more commonly found in left eye (p <
      0.001). The most common type of refractive error was astigmatism (61%). The depth
      of amblyopia was not associated with the gender (p = 0.864) or age (p = 0.341) of
      the subjects or the laterality of the eyes (p = 0.159), but it was associated
      with the type (p = 0.049) and magnitude (p = 0.013) of refractive error of the
      amblyopic eye and the magnitude of anisometropia (p = 0.002). CONCLUSION:
      Nepalese anisometropic amblyopic children were presented late to hospital. The
      depth of amblyopia was highly associated with the type and magnitude of
      refractive error of the amblyopic eye and the magnitude of anisometropia. So,
      basic vision screening programs may help to find out the anisometropic children
      and reefer them to the hospital for timely management of anisometropic amblyopia
      if present.

PMID- 24725214
TI  - Luminance and colour variant pupil perimetry in glaucoma.
AB  - BACKGROUND: This study investigated the diagnostic utility for glaucoma of
      multifocal pupillographic objective perimetry stimuli targeting different
      components of the pupillary response: cortically derived colour responses and
      subcortical luminance responses. DESIGN: Observational cross-sectional study
      undertaken at the Australian National University. PARTICIPANTS: Thirty-five eyes
      of 24 glaucoma subjects and 46 eyes of 23 normal subjects. METHODS: Subjects were
      tested with three multifocal pupillographic objective perimetry stimulus
      variants. The luminance-only variant (YYbal) utilized yellow stimuli on a yellow
      background; mixed colour and luminance protocols utilized green stimuli on a red
      background (RGbal, RG). Stimuli of 33 ms duration were presented at mean
      intervals of 4 s/region. MAIN OUTCOME MEASURES: Pupil constriction amplitude and
      time to peak. Area under the receiver operating characteristic curve was the main
      measure of sensitivity and specificity for glaucoma. RESULTS: Colour and
      luminance protocols were more accurate at differentiating glaucoma subjects from
      normal subjects than the luminance-only protocol, and produced the largest
      reductions in amplitudes. This type of protocol also produced the highest overall
      sensitivity and specificity for glaucoma (receiver operating characteristic %
      area under the curve: severe, 100%; moderate, 94.4%; mild, 71.0%). Pattern
      deviations tended to produce higher area under the receiver operating
      characteristic curves in eyes classified as mild. Significant differences in the
      means of the six worst amplitude deviations were observed between normal and
      severe glaucoma subjects only. CONCLUSIONS: Stimuli targeting both cortical
      pupillary colour response and subcortical pupillary luminance response components
      produced higher diagnostic accuracy than stimuli targeting subcortical pupillary
      luminance responses alone. Inclusion of constriction latencies further improved
      accuracy.

PMID- 24725216
TI  - Comprehensive analysis of Sichuan white geese (Anser cygnoides) transcriptome.
AB  - High-throughput RNA sequencing was performed for comprehensively analyzing the
      transcriptome of geese. A total of 28,803,759 bp of raw sequence data was
      generated by 454 GS Flx+. After removal of adaptor sequences, 28,730,361 bp
      remained and 117,279 reads were obtained, with an average length of 244 bases.
      Simultaneously, complementary DNA samples from two different reproductive stages
      of goose ovarian, hypothalamus and pituitary tissue were sequenced separately
      using Illumina MiSeq platform. A total of 12 688 673 148 bp of raw sequence data
      were generated by Illumina MiSeq. After removal of adaptor sequences, 8 198 126
      562 bp remained and 60 382 786 clean reads were obtained, with an average length
      of 135 bases. Assembly of all the reads from both 454 Flx+ and Illumina platforms
      formed 56,839 contigs. The sequence size ranges from 38 to 28,206 bp in size,
      with an average size of 2584 bp and an N50 of 4624. The assembly produced a
      substantial number of large contigs: 35,545 (62.5%) were longer than 1 kb, of
      which 8850 (15.6%) were longer than 5 kb. The sequencing depth was 85 X on
      average. We performed comprehensive function annotations on unigenes including
      protein sequence similarity, gene ontology (GO) term classification, and Kyoto
      Encylcopedia of Genes and Genomes (KEGG) pathway enrichment. GO analysis showed
      that approximately 63% of the contigs had annotation information, among the
      35,953 annotated isotigs in Nr database, 24,783 (68.9%) sequences were assigned
      with one or more GO terms. There were 14,634 (40.7%) isotigs for biological
      processes, 10,557(29.3%) isotigs for cellular component, 22,607 (62.9%) isotigs
      for molecular function. The result of KEGG pathway mapping 8926 sequences had the
      pathway annotation, and took part in 477 pathways. Additionally, 10,685 simple
      sequence repeat (SSR) markers were identified from the assembled sequences. The
      most frequent repeat motifs were trinucleotides, which accounted for 53.03% of
      all SSRs, followed by dinucleotides (39.9%), tetranucleotides (5.08%),
      pentanucleotides (1.68%) and hexanucleotides (0.32%). Transcriptome sequencing on
      mixture issue of the geese yielded substantial transcriptional sequences and
      potentially useful SSR markers which provide an important data source for geese
      research.

PMID- 24725217
TI  - Unambiguous characterization of N-glycans of monoclonal antibody cetuximab by
      integration of LC-MS/MS and 1H NMR spectroscopy.
AB  - Monoclonal antibodies are most rapidly emerging as therapeutic drugs for the
      treatment of cancer and of various other diseases such as autoimmunity or
      inflammation. Recently, it was found that nonhuman glycosylation of recombinant
      antibodies can cause tremendous problems for some patients. Therefore,
      unambiguous assignment of the glycosylation pattern of therapeutic antibodies is
      of high importance for assessment of human compatibility. Here we present results
      from a broad and detailed N-glycan analysis of the therapeutic antibody cetuximab
      by LC-MS/MS analyses tightly integrated with (1)H NMR to obtain unambiguous
      structures. Thirty-seven N-glycan compositions were identified by LC-MS(/MS).
      Subsequently, ten abundant structures were structurally characterized by applying
      the recently introduced method called three-dimensional cross correlation (3DCC).
      It was possible to extract NMR spectra of pure N-glycans that were heavily
      overlapping in a chromatographic separation by mathematically dissecting the NMR
      spectra obtained from chromatographic fractions. Even mass isobaric structures
      that differ only in the branching position of one monosaccharide unit were
      distinguished and characterized. We also developed an improvement of the 3DCC
      method by introducing singular value decomposition (SVD) for processing of the
      data. The smallest amount of the N-glycan characterized by 3DCC was approximately
      400 pmol (836 ng). Among the ten unambiguously identified glycans, six N-glycans,
      representing 24% of all detected glycans, possess the immunogenic alpha-1,3-Gal
      epitope and/or N-glycolylneuraminic acid. These results illustrate the importance
      of integrated use of LC-MS(/MS) and (1)H NMR for the glycome analysis of
      biopharmaceuticals in research, development, and quality control. 

PMID- 24725218
TI  - Perceived discrimination, humiliation, and mental health: a mixed-methods study
      among Haitian migrants in the Dominican Republic.
AB  - OBJECTIVE: Many Haitian migrants live and work as undocumented laborers in the
      Dominican Republic. This study examines the legacy of anti-Haitian discrimination
      in the Dominican Republic and association of discrimination with mental health
      among Haitian migrants. DESIGN: This study used mixed methods to generate
      hypotheses for associations between discrimination and mental health of Haitian
      migrants in the Dominican Republic. In-depth interviews were conducted with 21
      Haitian and 18 Dominican community members and clinicians. One hundred and twenty
      seven Haitian migrants participated in a pilot cross-sectional community survey.
      Instruments included culturally adapted Kreyol versions of the Beck Depression
      Inventory (BDI) and Beck Anxiety Inventory (BAI) and a locally developed function
      impairment scale. RESULTS: Haitian migrants described humiliation (imilyasyon) as
      a reason for mental distress and barrier to health care. Dominicans reported that
      discrimination (discriminacion) was not a current social problem and attributed
      negative social interactions to sociocultural, behavioral, and biological
      differences between Dominicans and Haitians. These qualitative findings were
      supported in the quantitative analyses. Perceived discrimination was
      significantly associated with depression severity and functional impairment.
      Perceived mistreatment by Dominicans was associated with a 6.6-point increase in
      BDI score (90% confidence interval [CI]: 3.29, 9.9). Knowing someone who was
      interrogated or deported was associated with a 3.4-point increase in BAI score
      (90% CI: 0.22, 6.64). CONCLUSION: Both qualitative and quantitative methods
      suggest that perceived discrimination and the experience of humiliation
      contribute to Haitian migrant mental ill-health and limit access to health care.
      Future research should evaluate these associations and identify intervention
      pathways for both improved treatment access and reduction of discrimination
      related health risk factors.

PMID- 24725219
TI  - Increased temporo-insular engagement in unmedicated bipolar II disorder: an
      exploratory resting state study using independent component analysis.
AB  - OBJECTIVES: Despite numerous structural and functional magnetic resonance imaging
      studies, the neurobiology of bipolar disorder (BD) is still incompletely
      understood. Resting-state functional magnetic resonance imaging (rsFMRI) allows
      for the study of intrinsic functional connections between brain areas, which may
      reflect the pathophysiology of BD. Most previous rsFMRI studies conducted in BD
      have included a majority of medicated patients, making simple interpretation with
      respect to pathophysiology difficult. METHODS: Participants were 15 antipsychotic
      agent- and mood-stabilizer-naive young adults with bipolar II disorder (BD-II),
      and 20 healthy controls group-matched for gender, age, and cognitive ability.
      Independent component analysis (ICA) was used to identify eight commonly studied
      resting-state networks (RSNs). Between-group comparisons were conducted using
      dual regression and corrected for family-wise error (FWE) across space and the
      number of components (pFWE < 0.05). RESULTS: In comparison to controls,
      participants with BD-II had increased coherence across several brain regions,
      including the bilateral insula and putamen, across a temporo-insular network. No
      between-group differences in engagement of the default mode network were found.
      CONCLUSIONS: This was the first ICA-based rsFMRI study conducted among
      unmedicated individuals with BD. Given the young age (mean = 23 years) and
      antipsychotic agent- and mood-stabilizer-naive status of our participants with BD
      II, temporo-insular functional connectivity is a candidate vulnerability marker
      for BD. Further work is needed to relate resting-state differences to detailed
      understanding of pathophysiology.

PMID- 24725220
TI  - Light alcohol intake during adolescence induces alcohol addiction in a
      neurodevelopmental model of schizophrenia.
AB  - Schizophrenia is a mental disorder characterized by a series of positive,
      negative or cognitive symptoms but with also the particularity of exhibiting a
      high rate of co-morbid use of drugs of abuse. While more than 80% of
      schizophrenics are smokers, the second most consumed drug is alcohol, with
      dramatic consequences on frequency and intensity of psychotic episodes and on
      life expectancy. Here we investigated the impact of light alcohol intake during
      adolescence on the subsequent occurrence of alcohol addiction-like behavior in
      neonatal ventral hippocampal lesion (NVHL) rats, a neurodevelopmental model of
      schizophrenia. Our findings demonstrated an increased liability to addictive
      behaviors in adult NVHL rats after voluntary alcohol intake during adolescence.
      NVHL rats displayed several signs of alcohol use disorder such as a loss of
      control over alcohol intake and high motivation to consume alcohol, associated
      with a higher resistance to extinction. In addition, once NVHL rats relapsed,
      they maintained higher drinking levels than controls. We finally showed that the
      anti-addictive drug naltrexone is efficient in reducing excessive alcohol intake
      in NVHL rats. Our results are in accordance with epidemiological studies
      underlying the particular vulnerability to alcohol addiction after adolescent
      exposure to alcohol and highlight the fact that schizophrenic subjects may be
      particularly at risk even after light alcohol consumption. Based on these
      results, it seems particularly relevant to prevent early onset of alcohol use in
      at-risk subjects and thus to reduce the incidence of co-morbid alcohol abuse in
      psychotic patients. 

PMID- 24725221
TI  - Determinants of self-care participation of young children with cerebral palsy.
AB  - OBJECTIVE: To test a model of child, family and service determinants of self-care
      participation of children with cerebral palsy (CP), grouped by Gross Motor
      Function Classification System levels (I-II and III-V). METHODS: Participants
      were a convenience sample of 429 children (242 males) with CP, aged 18-60 months.
      Data on impairments and gross motor function were collected by reliable
      therapists; parents provided information about children's health conditions and
      adaptive behaviour. Seven months later parents reported on family life and
      services received. One year after study onset, parents documented children's self
      care participation. Data from two groups of children were analysed using
      structural equation modelling. RESULTS: The model explained a significant
      proportion of the variance of self-care participation, with higher motor
      function, fewer health conditions and higher levels of adaptive behaviour being
      associated with greater self-care participation. CONCLUSION: Supporting
      children's gross motor function, health and adaptive behaviour may optimize self
      care participation.

PMID- 24725222
TI  - Boron substitution in aluminum cluster anions: magic clusters and reactivity with
      oxygen.
AB  - We have studied the size-selective reactivity of AlnBm(-) clusters m = 1,2 with
      O2 to investigate the effect of congener substitution in energetic aluminum
      clusters. Mixed-metal clusters offer an additional strategy for tuning the
      electronic and geometric structure of clusters and by substituting an atom with a
      congener; we may investigate the effect of structural changes in clusters with
      similar electronic structures. Using a fast-flow tube mass spectrometer, we
      formed aluminum boride cluster anions and exposed them to molecular oxygen. We
      found multiple stable species with Al12B(-) and Al11B2(-) being highly resistant
      to reactivity with oxygen. These clusters behave in a similar manner as Al13(-),
      which has previously been found to be stable in oxygen because of its icosahedral
      geometry and its filled electronic shell. Al13(-) and Al12B(-) have icosahedral
      structures, while Al11B2(-) forms a distorted icosahedron. All three of these
      clusters have filled electronic shells, and Al12B(-) has a larger HOMO-LUMO gap
      due to its compact geometry. Other cluster sizes are investigated, and the
      structures of the AlnB(-) series are found to have endohedrally doped B atoms, as
      do many of the AlnB2(-) clusters. The primary etching products are found to be a
      loss of two Al2O molecules, with boron likely to remain in the cluster. 

PMID- 24725223
TI  - Community health insurance as a catalyst for uptake of family planning and
      reproductive health services: the Obio Cottage Hospital experience.
AB  - Health service delivery in the Niger Delta region of Nigeria has suffered many
      setbacks. Community participation may help break the barriers limiting access to
      health services, especially those associated with family planning and
      reproductive health services. This is a two-year review of family planning and
      reproductive health services records offered by the Obio Cottage Hospital from
      the onset of the Community Insurance Scheme (2010-12). Since the inception of the
      Community Insurance Scheme, there has been an increase in the uptake of family
      planning methods of more than 50%; 1,274 women in 2011 vs 3,140 in 2012. An
      increase in number of women seeking reproductive health services was also
      observed. The Community Health Insurance Scheme (CHIS) at the Obio Cottage
      Hospital provides evidence for expansion, as seen in the improvement in patronage
      for family planning and reproductive health services.

PMID- 24725224
TI  - The temporary use of thrombopoietin-receptor agonists may induce a prolonged
      remission in adult chronic immune thrombocytopenia. Results of a French
      observational study.
AB  - Thrombopoietin-receptor agonists (Tpo-RAs) are highly effective in immune
      thrombocytopenia (ITP). Recently, cases of durable remission after Tpo-RA
      discontinuation in adult ITP have been reported. We aimed to describe the subset
      of patients in whom transient Tpo-RA therapy may induce a durable response. We
      studied all adults with primary ITP treated with at least one Tpo-RA over a 5
      year period (n = 54) and seen at one of three participating referral centres in
      France. Tpo-RAs were discontinued in 20 of 28 patients who achieved a complete
      response. We excluded six patients because a previous treatment at the start of
      Tpo-RA treatment may have interfered with the response. Overall, eight patients
      with chronic ITP showed a sustained response [median follow-up: 13.5 months
      (range 5-27 months)]. We could not identify a predictive factor of sustained
      response. In conclusion, a substantial proportion of ITP patients receiving Tpo
      RAs can maintain a durable response after treatment discontinuation. 

PMID- 24725225
TI  - Inferring climate from angiosperm leaf venation networks.
AB  - Leaf venation networks provide an integrative linkage between plant form,
      function and climate niche, because leaf water transport underlies variation in
      plant performance. Here, we develop theory based on leaf physiology that uses
      community-mean vein density to predict growing season temperature and atmospheric
      CO2 concentration. The key assumption is that leaf water supply is matched to
      water demand in the local environment. We test model predictions using leaves
      from 17 temperate and tropical sites that span broad climatic gradients. We find
      quantitative agreement between predicted and observed climate values. We also
      highlight additional leaf traits that may improve predictions. Our study provides
      a novel approach for understanding the functional linkages between functional
      traits and climate that may improve the reconstruction of paleoclimate from
      fossil assemblages. 

PMID- 24725226
TI  - Biphasic anaphylactic reactions: occurrence and mortality.
AB  - BACKGROUND: Monitoring after complete resolution of anaphylactic reactions is
      recommended. The aim of this study was to define the occurrence of biphasic - and
      clinically important biphasic - anaphylactic reactions, the number of transfers
      to intensive care units (ICU) because of anaphylaxis, and the number of deaths
      within 10 days of presentation to the emergency department (ED). METHODS:
      Clinical records of patients visiting the ED of a tertiary care hospital were
      analysed retrospectively. Hospital databases, direct contact with patients and
      caregivers, and the Internet were used to obtain mortality rates. RESULTS: Of 259
      557 ED presentations from February 2001 through to August 2013, 1334 (0.51%)
      episodes of allergic reactions were detected, and 532 (0.20%) episodes in 495
      patients fulfilled the definition of anaphylaxis. In 227 (44.8%) episodes, the
      length of hospital stay was >=8 h (median 22 h, IQR 16-24). There were 507
      uniphasic and 25 (4.5%) biphasic anaphylactic reactions. Twelve (2.3%) were
      clinically important, including 2 (0.36%) that occurred during hospital stay, one
      of whom (0.19%) was transferred to ICU for shock. No risk factors for biphasic
      reactions could be found. Eight patients were lost to follow-up. There were no
      deaths during the 10-day follow-up. CONCLUSION: Biphasic anaphylactic reactions,
      especially clinically important ones, occurred rarely, and no mortality was
      found, whether the monitoring was for >=8 h or for <8 h. Our study could motivate
      physicians to consider discharging patients after complete resolution of an
      anaphylactic reaction and to dispense with prolonged monitoring.

PMID- 24725227
TI  - Development of a PCR test system for specific detection of Salmonella Paratyphi B
      in foods.
AB  - Salmonella enterica serotype Paratyphi B is a globally distributed human-specific
      pathogen causing paratyphoid fever. The aim of this study was to develop a rapid
      and reliable polymerase chain reaction (PCR) assay for its detection in food. The
      SPAB_01124 gene was found to be unique to S. Paratyphi B using comparative
      genomics. Primers for fragments of the SPAB_01124 gene and the Salmonella
      specific invA gene were used in combination to establish a multiplex PCR assay
      that showed 100% specificity across 45 Salmonella strains (representing 34
      serotypes) and 18 non-Salmonella strains. The detection limit was 2.2 CFU mL(-1)
      of S. Paratyphi B after 12-h enrichment in pure culture. It was shown that co
      culture with S. Typhimurium or Escherichia coli up to concentrations of 3.6 *
      10(5)  CFU and 3.3 * 10(4)  CFU, respectively, did not interfere with PCR
      detection of S. Paratyphi B. In artificially contaminated milk, the assay could
      detect as few as 62 CFU mL(-1) after 8 h of enrichment. In conclusion,
      comparative genomics was found to be an efficient approach to the mining of
      pathogen-specific target genes, and the PCR assay that was developed from this
      provided a rapid, specific, and sensitive method for detection of S. Paratyphi B.

PMID- 24725228
TI  - Do nitric oxide-releasing drugs offer a potentially new paradigm for the
      management of cardiovascular risks in diabetes?
AB  - Cardiovascular complications are frequently observed in diabetic patients and are
      mostly caused by endothelial dysfunction associated with a decline in
      biosynthesis of nitric oxide (NO). In response to this concern, a remarkable
      increase in the interest for development of NO-releasing hybrid drugs has been
      observed. The NO-donating entity was linked to known drugs with the belief that
      NO is a vasorelaxant and an inhibitor of platelet aggregation or reduces
      thrombotic events. Many of these NO-releasing hybrid drugs have shown significant
      improvement in cardiovascular safety. In this editorial the potential roles of NO
      releasing drugs for the treatment of cardiovascular complications in diabetes
      will be discussed. 

PMID- 24725229
TI  - Association of bovine beta-casein protein variant I with milk production and milk
      protein composition.
AB  - The aim of this study was to detect new polymorphisms in the bovine beta-casein
      (beta-CN) gene and to evaluate association of (new) beta-CN protein variants with
      milk production traits and milk protein composition. Screening of the beta-CN
      gene in genomic DNA from 72 Holstein Friesian (HF) bulls resulted in detection of
      19 polymorphisms and revealed the presence of beta-CN protein variant I in the
      Dutch HF population. Studies of association of beta-CN protein variants with milk
      composition usually do not discriminate protein variant I from variant A2.
      Association of beta-CN protein variants with milk composition was studied in 1857
      first-lactation HF cows and showed that associations of protein variants A2 and I
      were quite different for several traits. beta-CN protein variant I was
      significantly associated with protein percentage and protein yield, and with
      alphas1 -casein (alphas1 -CN), alphas2 -casein (alphas2 -CN), kappa-casein (kappa
      CN), alpha-lactalbumin (alpha-LA), beta-lactoglobulin (beta-LG), casein index and
      casein yield. Inferring beta-kappa-CN haplotypes showed that beta-CN protein
      variant I occurred only with kappa-CN variant B. Consequently, associations of
      beta-kappa-CN haplotype IB with protein percentage, kappa-CN, alpha-LA, beta-LG
      and casein index are likely resulting from associations of kappa-CN protein
      variant B, while associations of beta-kappa-CN haplotype IB with alphas1 -CN and
      alphas2 -CN seem to be resulting from associations of beta-CN variant I. 

PMID- 24725230
TI  - A single nucleotide polymorphism in suppressor of cytokine signalling-2 is
      associated with growth and feed conversion efficiency in pigs.
AB  - Feed efficiency and growth are the most important traits in pig production, and
      very few genetic markers have been reported to be associated with feed
      efficiency. The suppressor of cytokine signalling-2 (encoded by SOCS2) is the
      main negative regulator of somatic growth, and the knockout of SOCS2 and
      naturally mutant mice have high-growth phenotypes. Porcine SOCS2 was selected as
      a primary positional candidate for feed efficiency, because it is located on
      chromosome 5q, in the vicinity of a Quantitative Trait Locus (QTL) region for
      food conversion ratio in pigs. Here, we report five single nucleotide
      polymorphisms identified by sequencing of the promoter region and exon 1. One PCR
      RFLP assay was designed for genotyping the polymorphism c.1667A > G (GenBank
      Accession No AY312266). Association analyses were performed in an Australian
      mapping resource pedigree population (PRDC-US43) for food conversion ratio,
      backfat, IGF1 level and growth traits and showed significant effects on average
      daily gain on test (ADG2) (P < 0.01) and marginal association with food
      conversion ratio (FCR) (P < 0.08). 

PMID- 24725231
TI  - Fine-mapping of a locus on linkage group 23 for sex determination in Nile tilapia
      (Oreochromis niloticus).
AB  - Genetic markers in tilapia species associated with loci affecting sex
      determination (SD), sex-specific mortality or both were mapped to linkage groups
      (LG) 1, 2, 3, 6 and 23. The objective of this study was to use these markers to
      fine-map the locus with the greatest effect on SD in Oreochromis niloticus. Our
      parental stock, full-sibs of Nile tilapia (Swansea origin), were divided into
      three groups: (i) untreated, (ii) feminized by diethylstilbestrol and (iii)
      masculinized by 17alpha-methyltestosterone. We analysed the first group for
      association of microsatellite markers representing these five LGs. The strongest
      association with gender was found on LG23 for marker UNH898 (chi(2) ; P=8.6*10(
      5) ). Allele 276 was found almost exclusively in males, and we hypothesized that
      this allele is a male-associated allele (MAA). Sex-reversed individuals were used
      for mating experiments with and without the segregating MAA. Mating of
      individuals lacking the MAA resulted in all-female progeny. Mating of two
      heterozygotes for MAA gave rise to 81 males and 30 females. Analysis of
      association between gender and genotypes identified the MAA in 98.6% of males as
      opposed to 8.0% of females (chi(2) ; P=2.5*10(-18) ). Eight markers that flank
      UNH898 were genotyped to map the locus on LG23 within a confidence interval of 16
      21 cM. Mating of homozygous individuals for MAA is underway for production of all
      male populations.

PMID- 24725232
TI  - Population studies and parentage testing for Arabian horses using 15
      microsatellite markers.

PMID- 24725233
TI  - An allelic ladder for eleven short tandem repeat loci for use in the cattle
      identity test.

PMID- 24725234
TI  - Protein-induced configuration transitions of polyelectrolyte-modified liquid
      crystal droplets.
AB  - Liquid crystal (LC) droplets dispersed in aqueous solution have emerged as an
      optical probe for sensing the adsorption and interaction of biological species at
      the LC/aqueous interface. In this paper, we modify the surface of 4-n-pentyl-4'
      cyanobiphenyl (5CB) LC droplets by the adsorption of positively charged
      poly(diallyldimethylammonium chloride) (PDADMAC) and poly(ethylenimine) (PEI)
      with different molecular weights at the 5CB/water interface. The PDADMAC and PEI
      modified 5CB droplets show a radial director configuration in aqueous solution
      with salt concentrations above 150 mM. The adsorption of negatively charged
      bovine serum albumin (BSA) on the positively charged PDADMAC and PEI-modified 5CB
      droplets through electrostatic interaction can induce the radial-to-bipolar
      configuration transition of the 5CB inside the droplets. We find that the
      concentration of BSA required to induce the configuration transition increases
      linearly with the decrease of the molecular weight of PDAMAC and PEI. Our results
      highlight the capability of the director configuration of LC droplets as an
      optical probe for sensing the interaction between proteins and polyelectrolytes
      at the LC/aqueous interface. 

PMID- 24725235
TI  - Inhibition of microbial pathogens using fruit and vegetable peel extracts.
AB  - The aim of the present work is to evaluate the antimicrobial potency of some
      vegetable and fruit peels. The extraction was done by individual cold percolation
      method using various solvents with increasing polarity (Hexane, ethyl acetate,
      acetone, methanol and aqueous). The antimicrobial activity was done by agar well
      diffusion assay against five Gram positive bacteria, five Gram negative bacteria
      and four fungi. All extracts demonstrated varied level of antimicrobial activity.
      The peel extracts showed highest zone of inhibition against Gram negative
      bacteria as compared to Gram positive bacteria and fungi. Amongst studied peel
      extracts Citrus limon followed by Manilkara zapota and Carica papaya showed good
      antimicrobial activity indicating its potency as a promising source of natural
      antimicrobics. The results confirm the belief that agro waste can be
      therapeutically used.

PMID- 24725236
TI  - Therapy for hepatitis C--the costs of success.

PMID- 24725237
TI  - ABT-450/r-ombitasvir and dasabuvir with ribavirin for hepatitis C with cirrhosis.
AB  - BACKGROUND: Interferon-containing regimens for the treatment of hepatitis C virus
      (HCV) infection are associated with increased toxic effects in patients who also
      have cirrhosis. We evaluated the interferon-free combination of the protease
      inhibitor ABT-450 with ritonavir (ABT-450/r), the NS5A inhibitor ombitasvir (ABT
      267), the nonnucleoside polymerase inhibitor dasabuvir (ABT-333), and ribavirin
      in an open-label phase 3 trial involving previously untreated and previously
      treated adults with HCV genotype 1 infection and compensated cirrhosis. METHODS:
      We randomly assigned 380 patients with Child-Pugh class A cirrhosis to receive
      either 12 or 24 weeks of treatment with ABT-450/r-ombitasvir (at a once-daily
      dose of 150 mg of ABT-450, 100 mg of ritonavir, and 25 mg of ombitasvir),
      dasabuvir (250 mg twice daily), and ribavirin administered according to body
      weight. The primary efficacy end point was a sustained virologic response 12
      weeks after the end of treatment. The rate of sustained virologic response in
      each group was compared with the estimated rate with a telaprevir-based regimen
      (47%; 95% confidence interval [CI], 41 to 54). A noninferiority margin of 10.5
      percentage points established 43% as the noninferiority threshold; the
      superiority threshold was 54%. RESULTS: A total of 191 of 208 patients who
      received 12 weeks of treatment had a sustained virologic response at post
      treatment week 12, for a rate of 91.8% (97.5% CI, 87.6 to 96.1). A total of 165
      of 172 patients who received 24 weeks of treatment had a sustained virologic
      response at post-treatment week 12, for a rate of 95.9% (97.5% CI, 92.6 to 99.3).
      These rates were superior to the historical control rate. The three most common
      adverse events were fatigue (in 32.7% of patients in the 12-week group and 46.5%
      of patients in the 24-week group), headache (in 27.9% and 30.8%, respectively),
      and nausea (in 17.8% and 20.3%, respectively). The hemoglobin level was less than
      10 g per deciliter in 7.2% and 11.0% of patients in the respective groups.
      Overall, 2.1% of patients discontinued treatment owing to adverse events.
      CONCLUSIONS: In this phase 3 trial of an oral, interferon-free regimen evaluated
      exclusively in patients with HCV genotype 1 infection and cirrhosis,
      multitargeted therapy with the use of three new antiviral agents and ribavirin
      resulted in high rates of sustained virologic response. Drug discontinuations due
      to adverse events were infrequent. (Funded by AbbVie; TURQUOISE-II
      ClinicalTrials.gov number, NCT01704755.).

PMID- 24725240
TI  - Development and validation of a nomogram predicting recurrence risk in women with
      symptomatic urinary tract infection.
AB  - OBJECTIVES: To develop and externally validate a novel nomogram predicting
      recurrence risk probability at 12 months in women after an episode of urinary
      tract infection. METHODS: The study included 768 women from Santa Maria
      Annunziata Hospital, Florence, Italy, affected by urinary tract infections from
      January 2005 to December 2009. Another 373 women with the same criteria enrolled
      at Santa Chiara Hospital, Trento, Italy, from January 2010 to June 2012 were used
      to externally validate and calibrate the nomogram. Univariate and multivariate
      Cox regression models tested the relationship between urinary tract infection
      recurrence risk, and patient clinical and laboratory characteristics. The
      nomogram was evaluated by calculating concordance probabilities, as well as
      testing calibration of predicted urinary tract infection recurrence with observed
      urinary tract infections. Nomogram variables included: number of partners, bowel
      function, type of pathogens isolated (Gram-positive/negative), hormonal status,
      number of previous urinary tract infection recurrences and previous treatment of
      asymptomatic bacteriuria. RESULTS: Of the original development data, 261 out of
      768 women presented at least one episode of recurrence of urinary tract infection
      (33.9%). The nomogram had a concordance index of 0.85. The nomogram predictions
      were well calibrated. This model showed high discrimination accuracy and
      favorable calibration characteristics. In the validation group (373 women), the
      overall c-index was 0.83 (P = 0.003, 95% confidence interval 0.51-0.99), whereas
      the area under the receiver operating characteristic curve was 0.85 (95%
      confidence interval 0.79-0.91). CONCLUSIONS: The present nomogram accurately
      predicts the recurrence risk of urinary tract infection at 12 months, and can
      assist in identifying women at high risk of symptomatic recurrence that can be
      suitable candidates for a prophylactic strategy.

PMID- 24725238
TI  - Ledipasvir and sofosbuvir for previously treated HCV genotype 1 infection.
AB  - BACKGROUND: Effective treatment for hepatitis C virus (HCV) genotype 1 infection
      in patients who have not had a sustained virologic response to prior interferon
      based therapy represents an unmet medical need. METHODS: We conducted a phase 3,
      randomized, open-label study involving patients infected with HCV genotype 1 who
      had not had a sustained virologic response after treatment with peginterferon and
      ribavirin, with or without a protease inhibitor. Patients were randomly assigned
      to receive the NS5A inhibitor ledipasvir and the nucleotide polymerase inhibitor
      sofosbuvir in a once-daily, fixed-dose combination tablet for 12 weeks,
      ledipasvir-sofosbuvir plus ribavirin for 12 weeks, ledipasvir-sofosbuvir for 24
      weeks, or ledipasvir-sofosbuvir plus ribavirin for 24 weeks. The primary end
      point was a sustained virologic response at 12 weeks after the end of therapy.
      RESULTS: Among the 440 patients who underwent randomization and were treated, 20%
      had cirrhosis and 79% had HCV genotype 1a infection. The rates of sustained
      virologic response were high in all treatment groups: 94% (95% confidence
      interval [CI], 87 to 97) in the group that received 12 weeks of ledipasvir
      sofosbuvir; 96% (95% CI, 91 to 99) in the group that received 12 weeks of
      ledipasvir-sofosbuvir and ribavirin; 99% (95% CI, 95 to 100) in the group that
      received 24 weeks of ledipasvir-sofosbuvir; and 99% (95% CI, 95 to 100) in the
      group that received 24 weeks of ledipasvir-sofosbuvir and ribavirin. No patient
      discontinued treatment owing to an adverse event. The most common adverse events
      were fatigue, headache, and nausea. CONCLUSIONS: Treatment with a once-daily,
      single-tablet regimen of ledipasvir and sofosbuvir resulted in high rates of
      sustained virologic response among patients with HCV genotype 1 infection who had
      not had a sustained virologic response to prior interferon-based treatment.
      (Funded by Gilead Sciences; ION-2 ClinicalTrials.gov number, NCT01768286.).

PMID- 24725241
TI  - Abstracts Thirty-fourth Annual Meeting of the Surgical Infection Society, May 1
      3, 2014, Baltimore, Maryland .

PMID- 24725243
TI  - Preparation and reactions of heteroarylmethylzinc reagents.
AB  - We report a general preparation of heteroarylmethylzinc chlorides by direct zinc
      insertion into heteroarylmethyl chlorides, along with a facile and
      straightforward synthesis of these heterocyclic chloromethyl precursors. We
      demonstrate that heteroarylmethylzinc reagents undergo various reactions
      including cross-couplings, allylations, acylations, and addition reactions to
      aldehydes, leading to polyfunctional heterocyclic products. Furthermore, these
      heteroaromatic zinc compounds prove to be versatile reagents for the preparation
      of various N- and O-heterocycles and give access to an analogue of a CB1
      modifier. 

PMID- 24725239
TI  - Ledipasvir and sofosbuvir for untreated HCV genotype 1 infection.
AB  - BACKGROUND: In phase 2 studies, treatment with the all-oral combination of the
      nucleotide polymerase inhibitor sofosbuvir and the NS5A inhibitor ledipasvir
      resulted in high rates of sustained virologic response among previously untreated
      patients with hepatitis C virus (HCV) genotype 1 infection. METHODS: We conducted
      a phase 3, open-label study involving previously untreated patients with chronic
      HCV genotype 1 infection. Patients were randomly assigned in a 1:1:1:1 ratio to
      receive ledipasvir and sofosbuvir in a fixed-dose combination tablet once daily
      for 12 weeks, ledipasvir-sofosbuvir plus ribavirin for 12 weeks, ledipasvir
      sofosbuvir for 24 weeks, or ledipasvir-sofosbuvir plus ribavirin for 24 weeks.
      The primary end point was a sustained virologic response at 12 weeks after the
      end of therapy. RESULTS: Of the 865 patients who underwent randomization and were
      treated, 16% had cirrhosis, 12% were black, and 67% had HCV genotype 1a
      infection. The rates of sustained virologic response were 99% (95% confidence
      interval [CI], 96 to 100) in the group that received 12 weeks of ledipasvir
      sofosbuvir; 97% (95% CI, 94 to 99) in the group that received 12 weeks of
      ledipasvir-sofosbuvir plus ribavirin; 98% (95% CI, 95 to 99) in the group that
      received 24 weeks of ledipasvir-sofosbuvir; and 99% (95% CI, 97 to 100) in the
      group that received 24 weeks of ledipasvir-sofosbuvir plus ribavirin. No patient
      in either 12-week group discontinued ledipasvir-sofosbuvir owing to an adverse
      event. The most common adverse events were fatigue, headache, insomnia, and
      nausea. CONCLUSIONS: Once-daily ledipasvir-sofosbuvir with or without ribavirin
      for 12 or 24 weeks was highly effective in previously untreated patients with HCV
      genotype 1 infection. (Funded by Gilead Sciences; ION-1 ClinicalTrials.gov number
      NCT01701401.).

PMID- 24725244
TI  - Intraoperative blood pressure and cerebral perfusion: strategies to clarify
      hemodynamic goals.
AB  - Blood pressure can vary considerably during anesthesia. If blood pressure falls
      outside the limits of cerebrovascular autoregulation, children can become at risk
      of cerebral ischemic or hyperemic injury. However, the blood pressure limits of
      autoregulation are unclear in infants and children, and these limits can shift
      after brain injury. This article will review autoregulation, considerations for
      the hemodynamic management of children with brain injuries, and research on
      autoregulation monitoring techniques. 

PMID- 24725245
TI  - Comorbid rat model of ischemia and beta-amyloid toxicity: striatal and cortical
      degeneration.
AB  - Levels of cerebral amyloid, presumably beta-amyloid (Abeta), toxicity and the
      incidence of cortical and subcortical ischemia increases with age. However,
      little is known about the severe pathological condition and dementia that occur
      as a result of the comorbid occurrence of this vascular risk factor and Abeta
      toxicity. Clinical studies have indicated that small ischemic lesions in the
      striatum are particularly important in generating dementia in combination with
      minor amyloid lesions. These cognitive deficits are highly likely to be caused by
      changes in the cortex. In this study, we examined the viability and morphological
      changes in microglial and neuronal cells, gap junction proteins (connexin43) and
      neuritic/axonal retraction (Fer Kinase) in the striatum and cerebral cortex using
      a comorbid rat model of striatal injections of endothelin-1 (ET1) and Abeta
      toxicity. The results demonstrated ventricular enlargement, striatal atrophy,
      substantial increases in beta-amyloid, ramified microglia and increases in
      neuritic retraction in the combined models of stroke and Abeta toxicity. Changes
      in connexin43 occurred equally in both groups of Abeta-treated rats, with and
      without focal ischemia. Although previous behavioral tests demonstrated
      impairment in memory and learning, the visual discrimination radial maze task did
      not show significant difference, suggesting the cognitive impairment in these
      models is not related to damage to the dorsolateral striatum. These results
      suggest an insight into the relationship between cortical/striatal atrophy,
      pathology and functional impairment. 

PMID- 24725246
TI  - A comparison of the sensitivity of four Staphylococcus aureus isolates to two
      chlorine-based disinfectants and an eco-friendly commercially available cleaning
      agent.
AB  - The aim of this study was to determine the effect of household bleach, a sodium
      dichloroisocyanurate (NaDCC)-based disinfectant and an eco-friendly cleaning
      agent (EFCA) on four Staphylococcus aureus strains, including two isolated from
      community infections. The products were assessed using the suspension (EN 1276)
      and surface (EN 13697) tests, while biofilm activity was determined using the 96
      well plate method. Bleach and NaDCC caused > 5 log reduction in viable counts
      within 5 min in suspension, whilst on surfaces the reduction was < 3 log. Bleach
      at 5000 ppm free available chlorine completely eradicated MSSA NCTC 13297 and PVL
      CA MSSA biofilms within 10 min, but not at 500 and 50 ppm, NaDCC was less
      effective against biofilms. The EFCA demonstrated no antimicrobial activity. It
      is of concern that at the recommended "use" dilution, bleach did not eradicate
      biofilms. Although increasing contact time and/or concentration should improve
      the activity, this may not be acceptable to the user.

PMID- 24725247
TI  - Prevalence of faecal incontinence in community-dwelling older people in Bali,
      Indonesia.
AB  - AIM: To explore the prevalence rate of faecal incontinence in community-dwelling
      older people, associated factors, impact on quality of life and practices in
      managing faecal incontinence. METHOD: Using a cross-sectional design, 600 older
      people aged 60+ were randomly selected from a population of 2916 in Bali,
      Indonesia using a simple random sampling technique. Three hundred and three
      participants were interviewed (response rate 51%). RESULTS: The prevalence of
      faecal incontinence was 22.4% (95% confidence interval (CI) 18.0-26.8). Self
      reported constipation (odds ratio (OR) 3.68, 95% CI 1.87-7.24) and loose stools
      (OR 2.66, 95% CI 1.47-4.78) were significantly associated with faecal
      incontinence. There was a strong positive correlation between total bowel control
      score and total quality-of-life score (P < 0.001, rs = 0.61) indicating
      significant alterations in quality of life. The current management practices
      varied from changing diet, visiting health-care professionals, and using modern
      and traditional medicines. CONCLUSION: Faecal incontinence is common among
      community-dwelling older people in Bali.

PMID- 24725248
TI  - Strong carbon-surface dative bond formation by tert-butyl isocyanide on the
      Ge(100)-2 * 1 surface.
AB  - Carbon dative bond formation between an organic molecule and a semiconductor
      surface is reported here for the first time. Our studies show that the adsorption
      of tert-butyl isocyanide on the (100) surface of germanium, measured using
      Fourier transform infrared spectroscopy, temperature-programmed desorption, and
      density functional theory calculations, occurs via formation of a dative bond to
      the surface through the isocyanide carbon. The experimentally observed adsorption
      energy of 26.8 kcal/mol is the largest among any organic molecule dative bonded
      on the Ge(100)-2 * 1 surface studied to date. The dative-bonded adsorbate is
      characterized by a N=C stretching frequency significantly blue-shifted from that
      of the free molecule. Moreover, the adsorbate N=C vibrational frequency red
      shifts back toward that of the free molecule upon increasing coverage. These
      spectroscopic effects are attributed to sigma-donation of the isocyanide lone
      pair electrons to the surface. 

PMID- 24725250
TI  - The frequency of TP53 gene defects differs between chronic lymphocytic leukaemia
      subgroups harbouring distinct antigen receptors.

PMID- 24725252
TI  - An evolutionary resolution of manipulation conflict.
AB  - Individuals can manipulate the behavior of social partners. However, manipulation
      may conflict with the fitness interests of the manipulated individuals.
      Manipulated individuals can then be favored to resist manipulation, possibly
      reducing or eliminating the manipulated behavior in the long run. I use a
      mathematical model to show that conflicts where manipulation and resistance
      coevolve can disappear as a result of the coevolutionary process. I find that
      while manipulated individuals are selected to resist, they can simultaneously be
      favored to express the manipulated behavior at higher efficiency (i.e., providing
      increasing fitness effects to recipients of the manipulated behavior). Efficiency
      can increase to a point at which selection for resistance disappears. This
      process yields an efficient social behavior that is induced by social partners,
      and over which the inducing and induced individuals are no longer in conflict. A
      necessary factor is costly inefficiency. I develop the model to address the
      evolution of advanced eusociality via maternal manipulation (AEMM). The model
      predicts AEMM to be particularly likely in taxa with ancestrally imperfect
      resistance to maternal manipulation. Costly inefficiency occurs if the cost of
      delayed dispersal is larger than the benefit of exploiting the maternal patch. I
      discuss broader implications of the process.

PMID- 24725251
TI  - Perspectives of germ cell development in vitro in mammals.
AB  - Pluripotent stem cells, such as embryonic stem cells (ESCs) and induced
      pluripotent stem cells (iPSCs) are able to differentiate into all cell lineages
      of the embryo proper, including germ cells. This pluripotent property has a huge
      impact on the fields of regenerative medicine, developmental biology and
      reproductive engineering. Establishing the germ cell lineage from ESCs/iPSCs is
      the key biological subject, since it would contribute not only to dissection of
      the biological processes of germ cell development but also to production of
      unlimited numbers of functional gametes in vitro. Toward this goal, we recently
      established a culture system that induces functional mouse primordial germ cells
      (PGCs), precursors of all germ cells, from mouse ESCs/iPSCs. The successful in
      vitro production of PGCs arose from the study of pluripotent cell state, the
      signals inducing PGCs and the technology of transplantation. However, there are
      many obstacles to be overcome for the robust generation of mature gametes or for
      application of the culture system to other species, including humans and
      livestock. In this review, we discuss the requirements for a culture system to
      generate the germ cell lineage from ESCs/iPSCs. 

PMID- 24725253
TI  - Biochemical characterization of eight genetic variants of human DNA polymerase
      kappa involved in error-free bypass across bulky N(2)-guanyl DNA adducts.
AB  - DNA polymerase (pol) kappa, one of the Y-family polymerases, has been shown to
      function in error-free translesion DNA synthesis (TLS) opposite the bulky N(2)
      guanyl DNA lesions induced by many carcinogens such as polycyclic aromatic
      hydrocarbons. We analyzed the biochemical properties of eight reported human pol
      kappa variants positioned in the polymerase core domain, using the recombinant
      pol kappa (residues 1-526) protein and the DNA template containing an N(2)-CH2(9
      anthracenyl)G (N(2)-AnthG). The truncation R219X was devoid of polymerase
      activity, and the E419G and Y432S variants showed much lower polymerase activity
      than wild-type pol kappa. In steady-state kinetic analyses, E419G and Y432S
      displayed 20- to 34-fold decreases in kcat/Km for dCTP insertion opposite G and
      N(2)-AnthG compared to that of wild-type pol kappa. The L21F, I39T, and D189G
      variants, as well as E419G and Y432S, displayed 6- to 22-fold decreases in
      kcat/Km for next-base extension from C paired with N(2)-AnthG, compared to that
      of wild-type pol kappa. The defective Y432S variant had 4- to 5-fold lower DNA
      binding affinity than wild-type, while a slightly more efficient S423R variant
      possessed 2- to 3-fold higher DNA-binding affinity. These results suggest that
      R219X abolishes and the E419G, Y432S, L21F, I39T, and D189G variations
      substantially impair the TLS ability of pol kappa opposite bulky N(2)-G lesions
      in the insertion step opposite the lesion and/or the subsequent extension step,
      raising the possibility that certain nonsynonymous pol kappa genetic variations
      translate into individual differences in susceptibility to genotoxic carcinogens.

PMID- 24725254
TI  - Barite in hydrothermal environments as a recorder of subseafloor processes: a
      multiple-isotope study from the Loki's Castle vent field.
AB  - Barite chimneys are known to form in hydrothermal systems where barium-enriched
      fluids generated by leaching of the oceanic basement are discharged and react
      with seawater sulfate. They also form at cold seeps along continental margins,
      where marine (or pelagic) barite in the sediments is remobilized because of
      subseafloor microbial sulfate reduction. We test the possibility of using
      multiple sulfur isotopes (delta34S, Delta33S, ?36S) of barite to identify
      microbial sulfate reduction in a hydrothermal system. In addition to multiple
      sulfur isotopes, we present oxygen (delta18O) and strontium (87Sr/86Sr) isotopes
      for one of numerous barite chimneys in a low-temperature (~20  degrees C) venting
      area of the Loki's Castle black smoker field at the ultraslow-spreading Arctic
      Mid-Ocean Ridge (AMOR). The chemistry of the venting fluids in the barite field
      identifies a contribution of at least 10% of high-temperature black smoker fluid,
      which is corroborated by 87Sr/86 Sr ratios in the barite chimney that are less
      radiogenic than in seawater. In contrast, oxygen and multiple sulfur isotopes
      indicate that the fluid from which the barite precipitated contained residual
      sulfate that was affected by microbial sulfate reduction. A sulfate reduction
      zone at this site is further supported by the multiple sulfur isotopic
      composition of framboidal pyrite in the flow channel of the barite chimney and in
      the hydrothermal sediments in the barite field, as well as by low SO4 and
      elevated H2S concentrations in the venting fluids compared with conservative
      mixing values. We suggest that the mixing of ascending H2- and CH4-rich high
      temperature fluids with percolating seawater fuels microbial sulfate reduction,
      which is subsequently recorded by barite formed at the seafloor in areas where
      the flow rate is sufficient. Thus, low-temperature precipitates in hydrothermal
      systems are promising sites to explore the interactions between the geosphere and
      biosphere in order to evaluate the microbial impact on these systems.

PMID- 24725255
TI  - Emission of herbivore elicitor-induced sesquiterpenes is regulated by stomatal
      aperture in maize (Zea mays) seedlings.
AB  - Maize seedlings emit sesquiterpenes during the day in response to insect
      herbivory. Parasitoids and predators use induced volatile blends to find their
      hosts or prey. To investigate the diurnal regulation of biosynthesis and emission
      of induced sesquiterpenes, we applied linolenoyl-L-glutamine (LG) to maize
      seedlings in the morning or evening using a cut-stem assay and tracked farnesene
      emission, in planta accumulation, as well as transcript levels of farnesyl
      pyrophosphate synthase 3 (ZmFPPS3) and terpene synthase10 (ZmTPS10) throughout
      the following day. Independent of time of day of LG treatment, maximum transcript
      levels of ZmFPPS3 and ZmTPS10 occurred within 3-4 h after elicitor application.
      The similarity between the patterns of farnesene emission and in planta
      accumulation in light-exposed seedlings in both time courses suggested
      unobstructed emission in the light. After evening induction, farnesene
      biosynthesis increased dramatically during early morning hours. Contrary to light
      exposed seedlings dark-kept seedlings retained the majority of the synthesized
      farnesene. Two treatments to reduce stomatal aperture, dark exposure at midday,
      and abscisic acid treatment before daybreak, resulted in significantly reduced
      amounts of emitted and significantly increased amounts of in planta accumulating
      farnesene. Our results suggest that stomata not only play an important role in
      gas exchange for primary metabolism but also for indirect plant defences. 

PMID- 24725256
TI  - Genome-wide survey of transcriptional initiation in the pathogenic fungus,
      Candida glabrata.
AB  - DNA sequencing of the 5'-flanking region of the transcriptome effectively
      identifies transcription initiation sites and also aids in identifying unknown
      genes. This study describes a comprehensive polling of transcription start sites
      and an analysis of full-length complementary DNAs derived from the genome of the
      pathogenic fungus Candida glabrata. A comparison of the sequence reads derived
      from a cDNA library prepared from cells grown under different culture conditions
      against the reference genomic sequence of the Candida Genome Database (CGD:
      http://www.candidagenome.org/) revealed the expression of 4316 genes and their
      acknowledged transcription start sites (TSSs). In addition this analysis also
      predicted 59 new genes including 22 that showed no homology to the genome of
      Saccharomyces cerevisiae, a genetically close relative of C. glabrata.
      Furthermore, comparison of the 5'-untranslated regions (5'-UTRs) and core
      promoters of C. glabrata to those of S. cerevisiae showed various global
      similarities and differences among orthologous genes. Thus, the C. glabrata
      transcriptome can complement the annotation of the genome database and should
      provide new insights into the organization, regulation, and function of genes of
      this important human pathogen. 

PMID- 24725257
TI  - Molecular analysis of cell-free circulating DNA for the diagnosis of somatic
      mutations associated with resistance to tyrosine kinase inhibitors in non-small
      cell lung cancer.
AB  - In non-small-cell lung cancer, the molecular diagnosis of somatic mutations is
      instrumental for the choice of the most appropriate treatment. However, despite
      an initial response, resistance to tyrosine kinase inhibitors occurs and
      thereafter tumors progress. For this reason, next generation inhibitors able to
      overcome acquired resistances are currently in development. Therefore, the
      identification of the molecular determinants of resistance is needed to adapt
      treatment accordingly. The analysis of circulating cell-free tumor DNA represents
      a powerful tool to monitor the somatic changes induced by treatment. This review
      focuses on the most recent advantages in the diagnosis of acquired resistance in
      circulating cell-free tumor DNA and underlines the strategies ready to be
      translated in the clinical practice.

PMID- 24725258
TI  - Evaluating an early intervention in psychosis service for 'high-risk'
      adolescents: symptomatic and social recovery outcomes.
AB  - AIM: This study presents client characteristics and treatment outcomes for a
      group of young people seen by Central Norfolk Early Intervention Team (CNEIT).
      The team offers an intensive outreach model of treatment to young people with
      complex co-morbid emotional, behavioural and social problems, as well as the
      presence of psychotic symptoms. METHODS: Outcomes include both client self-report
      and clinician-rated measures. Data are routinely collected at acceptance into
      service, after 12 months of service and at point of discharge. RESULTS: Data show
      that clients seen by the CNEIT youth team are a group of young people at high
      risk of developing long-term mental illness and social disability. Outcomes show
      significant reductions in not only psychotic symptomatology, but also co-morbid
      anxiety and depression, as well as improvements in social recovery. At the end of
      their time with the service, the majority of clients are discharged back to the
      care of their general practitioner, which indicates that the team successfully
      managed to reduce the complexity of needs and difficulties associated with this
      client group. CONCLUSIONS: Outcomes support the use of an intensive outreach
      approach for young people at high risk of developing psychotic disorders. It has
      been suggested that this model may be successfully broadened to young people with
      other emerging, potentially severe or complex mental disorders. Norfolk and
      Suffolk NHS Foundation Trust has built on the success of its youth early
      intervention team and innovatively redesigned its services in line with this
      model by developing a specific youth mental health service.

PMID- 24725259
TI  - In vivo assessment by Mach-Zehnder double-beam interferometry of the invasive
      force exerted by the Asian soybean rust fungus (Phakopsora pachyrhizi).
AB  - Asian soybean rust (Phakopsora pachyrhizi) causes a devastating disease in
      soybean (Glycine max). We tested the hypothesis that the fungus generates high
      turgor pressure in its hyaline appressoria to mechanically pierce epidermal
      cells. Turgor pressure was determined by a microscopic technique, called
      transmitted light double-beam interference Mach-Zehnder microscopy (MZM), which
      was developed in the 1960s as a forefront of live cell imaging. We revitalized
      some original microscopes and equipped them for modern image capturing. MZM data
      were corroborated by cytorrhysis experiments. Incipient cytorrhysis determined
      the turgor pressure in appressoria of P. pachyrhizi to be equivalent to 5.13 MPa.
      MZM data revealed that osmotically active sugar alcohols only accounted for 75%
      of this value. Despite having a lower turgor pressure, hyaline rust appressoria
      were able to penetrate non-biodegradable polytetrafluoroethylene (PTFE) membranes
      more efficiently than do melanized appressoria of the anthracnose fungus
      Colletotrichum graminicola or the rice blast fungus Magnaporthe oryzae. Our
      findings challenge the hypotheses that force-based penetration is a specific
      hallmark of fungi differentiating melanized appressoria and that this turgor
      driven process is solely caused by metabolic degradation products. The
      appressorial turgor pressure may explain the capability of P. pachyrhizi to
      forcefully invade a wide range of different plants and may pave the way to novel
      plant protection approaches. 

PMID- 24725260
TI  - Photochemical kinetics of pyruvic acid in aqueous solution.
AB  - Pyruvic acid in the atmosphere is found in both the gas and aqueous phases, and
      its behavior gives insight into that of other alpha-keto acids. Photolysis is a
      significant degradation pathway for this molecule in the environment, and in
      aqueous solution the major photoproducts are higher-molecular-weight compounds
      that may contribute to secondary organic aerosol mass. The kinetics of the
      aqueous-phase photolysis of pyruvic acid under aerobic and anaerobic conditions
      was investigated in order to calculate the first-order rate constant, Jaq, in
      solution. Analysis of the exponential decay of pyruvic acid was performed by
      monitoring both pyruvic acid and its photolytic products over the course of the
      reaction by (1)H NMR spectroscopy. Detection of major and minor products in the
      0.1, 0.05, and 0.02 M pyruvic acid photolyses clearly demonstrates that the
      primary reaction pathways are highly dependent on the initial pyruvic acid
      concentration and the presence of dissolved oxygen. The Jaq values were
      calculated with approximations based on the dominant pathways for limiting cases
      of the mechanism. Finally, a model study using the calculated rate constants
      demonstrates the importance of aqueous-phase photolysis as a sink for pyruvic
      acid in the atmosphere, compared with gas-phase photolysis and OH oxidation. 

PMID- 24725261
TI  - Pharyngeal spasticity due to dantrolene.
AB  - WHAT IS KNOWN AND OBJECTIVE: Dantrolene can be combined with baclofen to better
      treat spasticity, but may cause muscular weakness and dysphagia. We instead
      describe a pharyngeal spasm due to dantrolene. CASE SUMMARY: A 12-year-old male
      received dantrolene 3 mg/kg/day in adjunct to baclofen 2 mg/kg/day, to improve
      spasticity. After 5 days of full-dose dantrolene, his dysphagia worsened and he
      developed pharyngeal spasm. Dantrolene was suspected for an adverse reaction and
      removed. The patient subsequently improved. WHAT IS NEW AND CONCLUSION: Causality
      analysis determined a probable relationship between dantrolene and pharyngeal
      spasm. This may be due to direct muscle contraction by dantrolene, an effect seen
      previously in vitro.

PMID- 24725262
TI  - Living donor liver transplantation using a right liver graft with additional vein
      reconstructions for patient with situs inversus.
AB  - Living donor liver transplantation (LDLT) using a right liver graft with
      additional vein reconstructions has not been previously reported in a situs
      inversus (SI) patient. A 60-year-old man with SI was referred for LDLT for end
      stage cirrhosis secondary to hepatitis B. The calculated regional volumes of the
      individual hepatic vein territories in the right liver graft suggested that the
      middle hepatic vein (MHV) tributaries and the inferior right hepatic veins
      (IRHVs) should be reconstructed in addition to the right hepatic vein (RHV). On
      the back-table, the recipient's recanalized umbilical vein graft was anastomosed
      to the V5 opening, and the other side of vein graft was anastomosed to the RHV
      and V8 opening to create a large single orifice. After total hepatectomy, the
      right liver graft was placed in the left subphrenic space at the reversed
      position. The common orifice of hepatic venous drainage from RHV, V8 and V5 was
      anastomosed to the anatomical RHV conduit of the recipient, followed by IRHV
      anastomosis to the inferior vena cava. Postoperative course was almost
      uneventful, and no vascular complications were experienced. Even for SI patients,
      LDLT using a right liver graft with reconstructions of the MHV tributaries and
      the IRHVs is feasible. 

PMID- 24725263
TI  - Molecular-level surface structure from nonlinear vibrational spectroscopy
      combined with simulations.
AB  - Vibrational sum-frequency generation spectroscopy is valued for its ability to
      selectively probe molecules at a variety of interfaces without the use of
      extrinsic chromophores. The spectra contain valuable information regarding the
      molecular structure and the interfacial environment through the observation of
      vibrational resonances associated with specific moieties. Chemical information is
      obtained by close inspection of the frequencies of these bands and the amplitude
      of the response under conditions of different beam polarizations. Such
      sensitivity motivates the development of techniques that can provide structural
      details. We illustrate several approaches by which various types of calculations
      and molecular simulations may be used to enhance the sought structural
      interpretation of experimental data. By applying these techniques to the
      adsorbate molecules, interfacial water, and the substrate surfaces themselves, we
      are able to achieve a holistic picture of the adsorption environment. 

PMID- 24725264
TI  - Endoscopic pediatric neurosurgery: implications for anesthesia.
AB  - Endoscopic surgery is increasingly utilized in neurosurgery for all pediatric age
      groups. Endoscopic intraventricular neurosurgery represents a unique approach to
      intracranial pathology but may cause a unique set of limitations and potential
      complications. Important endoscopic neurosurgical techniques and their
      indications, perioperative anesthesia management, complications, and success
      rates are reviewed with special emphasis on endoscopic third ventriculostomy and
      endoscopic-assisted strip craniectomy in early infancy. Despite encouraging short
      and long-term results of early pediatric endoscopic neurosurgery, multicenter
      randomized studies will be needed to further determine safety and the effect on
      cognitive development and quality of life. 

PMID- 24725265
TI  - Development of self-efficacy of newly graduated registered nurses in an aged care
      program.
AB  - AIM: To evaluate an aged care program in developing self-efficacy of newly
      graduated registered nurses. METHODS: An evaluation of the program was conducted
      using a mixed methods approach. Twenty-four nurses completed the pre- and post
      survey of aged care nursing self efficacy and attended one of three focus groups
      held to gain in-depth understanding of their insight into the program. RESULTS:
      There was an increase in nurses' self-efficacy post-program. The increased self
      efficacy and new knowledge gained enhanced nurses' confidence and enabled them to
      critically appraise their workplace practices. CONCLUSIONS: The improved
      confidence resulting from increased self-efficacy and new knowledge gained from
      the aged care program enabled nurses to critically appraise the practices in
      their workplace, demonstrating the program's effectiveness. Aged care service
      providers should support continuing education for aged care nurses to ensure
      sustainability of a competent workforce to manage the increasing aged care
      population.

PMID- 24725267
TI  - Thank you for your support!

PMID- 24725266
TI  - Genome-wide characterization and comparative analysis of R2R3-MYB transcription
      factors shows the complexity of MYB-associated regulatory networks in Salvia
      miltiorrhiza.
AB  - BACKGROUND: MYB is the largest plant transcription factor gene family playing
      vital roles in plant growth and development. However, it has not been
      systematically studied in Salvia miltiorrhiza, an economically important
      medicinal plant. RESULTS: Here we report the genome-wide identification and
      characterization of 110 R2R3-MYBs, the largest subfamily of MYBs in S.
      miltiorrhiza. The MYB domain and other motifs of SmMYBs are largely conserved
      with Arabidopsis AtMYBs, whereas the divergence of SmMYBs and AtMYBs also exists,
      suggesting the conservation and diversity of plant MYBs. SmMYBs and AtMYBs may be
      classified into 37 subgroups, of which 31 include proteins from S. miltiorrhiza
      and Arabidopsis, whereas 6 are specific to a species, indicating that the
      majority of MYBs play conserved roles, while others may exhibit species
      specialized functions. SmMYBs are differentially expressed in various tissues of
      S. miltiorrhiza. The expression profiles are largely consistent with known
      functions of their Arabidopsis counterparts. The expression of a subset of SmMYBs
      is regulated by microRNAs, such as miR159, miR319, miR828 and miR858. Based on
      functional conservation of MYBs in a subgroup, SmMYBs potentially involved in the
      biosynthesis of bioactive compounds were identified. CONCLUSIONS: A total of 110
      R2R3-MYBs were identified and analyzed. The results suggest the complexity of MYB
      mediated regulatory networks in S. miltiorrhiza and provide a foundation for
      understanding the regulatory mechanism of SmMYBs.

PMID- 24725268
TI  - Factors influencing the effectiveness of multisource feedback in improving the
      professional practice of medical doctors: a systematic review.
AB  - BACKGROUND: Multisource feedback (MSF) is currently being introduced in the UK as
      part of a cycle of performance review for doctors. However, although it is
      suggested that the provision of feedback can lead to a positive change in
      performance and learning for medical professionals, the evidence supporting these
      assumptions is unclear. The aim of this review, therefore, was to identify the
      key factors that influence the effectiveness of multisource feedback in improving
      the professional practice of medical doctors. METHOD: Relevant electronic
      bibliographic databases were searched for studies that aimed to assess the impact
      of MSF on professional practice. Two reviewers independently selected and quality
      assessed the studies and abstracted data regarding study design, setting, MSF
      instrument, behaviour changes identified and influencing factors using a standard
      data extraction form. RESULTS: A total of 16 studies met the inclusion criteria
      and quality assessment criteria. While seven studies reported only a general
      change in professional practice, a further seven studies identified specific
      changes in behaviour. The main professional behaviours that were found to be
      influenced by the feedback were communication, both with colleagues and patients
      and an improvement in clinical competence/skills. The main factors found to
      influence the acceptance and use of MSF were the format of the feedback,
      specifically in terms of whether it was facilitated, or if narrative comments
      were included in the review, and if the feedback was from sources that the
      physician believed to be knowledgeable and credible. CONCLUSIONS: While there is
      limited evidence suggesting that MSF can influence professional performance, the
      quality of this evidence is variable. Further research is necessary to establish
      how this type of feedback actually influences behaviours and what factors have
      greatest influence.

PMID- 24725269
TI  - Trends in television time, non-gaming PC use and moderate-to-vigorous physical
      activity among German adolescents 2002-2010.
AB  - BACKGROUND: Studies in youth highlight that moderate-to-vigorous physical
      activity (MVPA) and screen-time behaviours such as television viewing and PC use
      are associated with a range of health outcomes. However, little is known about
      recent trends in these behaviours in adolescents. This paper presents time trends
      in German adolescents' television time, non-gaming PC use as well as MVPA from
      2002 to 2010. METHODS: Data were derived from the cross-sectional German Health
      Behaviour in School-aged Children (HBSC) study in 2002, 2006 and 2010. Analyses
      were based on 16,918 11-to 15-year olds boys (49.1%) and girls. Outcome variables
      were time spent in TV viewing and using a PC (weekday and weekend day) as well as
      the number of days achieving 60 minutes of MVPA. Changes in both screen-time
      behaviours and MVPA over time were analysed using sex-specific linear regression,
      controlling for age and family affluence. RESULTS: TV viewing on weekdays, but
      not at weekends, declined steadily over time with a difference between 2002 and
      2010 of 12.4 min/day in girls and 18.3 min/day in boys (p for trend<.01). We
      found a strong increase in PC use for non-gaming purposes over time for girls
      only, with a difference between 2002 and 2010 of 54.1 min/weekday and 68.8
      min/weekend day (p<.001). For MVPA we found a slight statistically significant
      increase in terms of meeting PA guidelines as well as days/week in MVPA for boys
      and girls (p<.001). In 2010 14.0% of girls and 19.9% of boys met PA guideline.
      CONCLUSION: Although MVPA increased from 2002 to 2010 in German adolescents, the
      time spent in MVPA was still low. Despite the observed decrease in TV viewing,
      there was no overall decline in the observed screen-based behaviours, especially
      for girls. This is mainly due to a marked increase in use of a PC for chatting on
      line, internet, emailing, homework etc. among girls during the last ten years
      which outweighs the corresponding decrease in TV viewing. The findings highlight
      a need for strategies and interventions aimed at reducing screen-time behaviours
      and promoting MVPA.

PMID- 24725270
TI  - Dilution cultivation of marine heterotrophic bacteria abundant after a spring
      phytoplankton bloom in the North Sea.
AB  - The roles of individual bacterioplankton species in the re-mineralization of
      algal biomass are poorly understood. Evidence from molecular data had indicated
      that a spring diatom bloom in the German Bight of the North Sea in 2009 was
      followed by a rapid succession of uncultivated bacterioplankton species,
      including members of the genera Ulvibacter, Formosa, Polaribacter (class
      Flavobacteria) and Reinekea (class Gammaproteobacteria). We isolated strains from
      the same site during the diatom bloom in spring 2010 using dilution cultivation
      in an artificial seawater medium with micromolar substrate and nutrient
      concentrations. Flow cytometry demonstrated growth from single cells to densities
      of 10(4) -10(6) cells ml(-1) and a culturability of 35%. Novel Formosa,
      Polaribacter and Reinekea strains were isolated and had 16S rRNA gene sequence
      identities of > 99.8% with bacterioplankton in spring or summer 2009. Genomes of
      selected isolates were draft sequenced and used for read recruitment of
      metagenomes from bacterioplankton in 2009. Metagenome reads covered 93% of a
      Formosa clade B, 91% of a Reinekea and 74% of a Formosa clade A genome, applying
      a >= 94.5% nucleotide identity threshold. These novel strains represent abundant
      bacterioplankton species thriving on coastal phytoplankton blooms in the North
      Sea.

PMID- 24725271
TI  - Iron-catalyzed cross-dehydrogenative coupling esterification of unactive C(sp3)-H
      bonds with carboxylic acids for the synthesis of alpha-acyloxy ethers.
AB  - An iron-catalyzed oxidative esterification reaction between unactivated C(sp(3))
      H bonds from symmetric and asymmetric ethers and carboxylic acids using di-tert
      butyl peroxide (DTBP) as the oxidant via a cross dehydrogenative coupling (CDC)
      reaction was established, which tolerates a wide range of cyclic ether substrates
      to react with aromatic acids and phenylacetic acid, providing an efficient method
      for the preparation of alpha-acyloxy ethers with good to excellent yields.
      Intermolecular competing kinetic isotope effect (KIE) experiments were also
      carried out, which indicate that C(sp(3))-H bond cleavage may be the rate
      determining step of this CDC reaction. 

PMID- 24725272
TI  - Open conformation of hERG channel turrets revealed by a specific scorpion toxin
      BmKKx2.
AB  - BACKGROUND: The human ether-a-go-go-related gene potassium channel (hERG) has an
      unusual long turret, whose role in recognizing scorpion toxins remains
      controversial. Here, BmKKx2, the first specific blocker of hERG channel derived
      from scorpion Mesobuthus martensii, was identified and the turret role of hERG
      channel was re-investigated using BmKKx2 as a molecular probe. RESULTS: BmKKx2
      was found to block hERG channel with an IC50 of 6.7 +/- 1.7 nM and share similar
      functional surface with the known hERG channel inhibitor BeKm-1. The alanine
      scanning mutagenesis data indicate that different residue substitutions on hERG
      channel by alanine decreased the affinities of toxin BmKKx2 by about 10-fold
      compared with that of wild-type hERG channel, which reveals that channel turrets
      play a secondary role in toxin binding. Different from channel turret, the pore
      region of hERG channel was found to exert the conserved and essential function
      for toxin binding because the mutant hERG-S631A channel remarkably decreased
      toxin BmKKx2 affinity by about 104-fold. CONCLUSIONS: Our results not only
      revealed that channel turrets of hERG channel formed an open conformation in
      scorpion toxin binding, but also enriched the diversity of structure-function
      relationships among the different potassium channel turrets.

PMID- 24725273
TI  - In vitro uptake of apoptotic body mimicking phosphatidylserine-quantum dot
      micelles by monocytic cell line.
AB  - A new quantum dot (QD) PEGylated micelle laced with phosphatidylserine (PS) for
      specific scavenger receptor-mediated uptake by macrophages is reported. The size
      and surface chemistry of PS-QD micelles were characterized by standard methods
      and the effects of their physicochemical properties on specific targeting and
      uptake were comprehensively studied in a monocytic cell line (J774A.1). 

PMID- 24725275
TI  - Bioelectrochemical oxidation of water.
AB  - The electrolysis of water provides a link between electrical energy and hydrogen,
      a high energy density fuel and a versatile energy carrier, but the process is
      very expensive. Indeed, the main challenge is to reduce energy consumption for
      large-scale applications using efficient renewable catalysts that can be produced
      at low cost. Here we present for the first time that laccase can catalyze
      electrooxidation of H2O to molecular oxygen. Native and laboratory-evolved
      laccases immobilized onto electrodes serve as bioelectrocatalytic systems with
      low overpotential and a high O2 evolution ratio against H2O2 production during
      H2O electrolysis. Our results open new research ground on H2O splitting, as they
      overcome serious practical limitations associated with artificial
      electrocatalysts currently used for O2 evolution. 

PMID- 24725274
TI  - Essential role for the TRF2 telomere protein in adult skin homeostasis.
AB  - TRF2 is a component of shelterin, the protein complex that protects the ends of
      mammalian chromosomes. TRF2 is essential for telomere capping owing to its roles
      in suppressing an ATM-dependent DNA damage response (DDR) at chromosome ends and
      inhibiting end-to-end chromosome fusions. Mice deficient for TRF2 are early
      embryonic lethal. However, the role of TRF2 in later stages of development and in
      the adult organism remains largely unaddressed, with the exception of liver,
      where TRF2 was found to be dispensable for maintaining tissue function. Here, we
      study the impact of TRF2 conditional deletion in stratified epithelia by
      generating the TRF2(?/?) -K5-Cre mouse model, which targets TRF2 deletion to the
      skin from embryonic day E11.5. In marked contrast to TRF2 deletion in the liver,
      TRF2(?/?) -K5-Cre mice show lethality in utero reaching 100% lethality
      perinataly. At the molecular and cellular level, TRF2 deletion provokes induction
      of an acute DDR at telomeres, leading to activation of p53 signaling pathways and
      to programed cell death since the time of Cre expression at E11.5. Unexpectedly,
      neither inhibition of the NHEJ pathway by abrogation of 53BP1 nor inhibition of
      DDR by p53 deficiency rescued these severe phenotypes. Instead, TRF2 deletion
      provokes an extensive epidermal cell death accompanied by severe inflammation
      already at E16.5 embryos, which are independent of p53. These results are in
      contrast with conditional deletion of TRF1 and TPP1 in the skin, where p53
      deficiency rescued the associated skin phenotypes, highlighting the comparatively
      more essential role of TRF2 in skin homeostasis. 

PMID- 24725277
TI  - Atrial dissection-like appearance caused by an inferior sinus venosus atrial
      septal defect with an unroofed defect.

PMID- 24725276
TI  - A pilot study of respiratory muscle training to improve cough effectiveness and
      reduce the incidence of pneumonia in acute stroke: study protocol for a
      randomized controlled trial.
AB  - BACKGROUND: After stroke, pneumonia is a relevant medical complication that can
      be precipitated by aspiration of saliva, liquids, or solid food. Swallowing
      difficulty and aspiration occur in a significant proportion of stroke survivors.
      Cough, an important mechanism protecting the lungs from inhaled materials, can be
      impaired in stroke survivors, and the likely cause for this impairment is central
      weakness of the respiratory musculature. Thus, respiratory muscle training in
      acute stroke may be useful in the recovery of respiratory muscle and cough
      function, and may thereby reduce the risk of pneumonia. The present study is a
      pilot study, aimed at investigating the validity and feasibility of this approach
      by exploring effect size, safety, and patient acceptability of the intervention.
      METHODS/DESIGN: Adults with moderate to severe stroke impairment (National
      Institutes of Health Stroke Scale (NIHSS) score 5 to 25 at the time of admission)
      are recruited within 2 weeks of stroke onset. Participants must be able to
      perform voluntary respiratory maneuvers. Excluded are patients with increased
      intracranial pressure, uncontrolled hypertension, neuromuscular conditions other
      than stroke, medical history of asthma or chronic obstructive pulmonary disease,
      and recent cardiac events. Participants are randomized to receive inspiratory,
      expiratory, or sham respiratory training over a 4-week period, by using
      commercially available threshold resistance devices. Participants and caregivers,
      but not study investigators, are blind to treatment allocation. All participants
      receive medical care and stroke rehabilitation according to the usual standard of
      care. The following assessments are conducted at baseline, 4 weeks, and 12 weeks:
      Voluntary and reflex cough flow measurements, forced spirometry, respiratory
      muscle strength tests, incidence of pneumonia, assessments of safety parameters,
      and self-reported activity of daily living. The primary outcome is peak
      expiratory cough flow of voluntary cough, a parameter indicating the
      effectiveness of cough. Secondary outcomes are incidence of pneumonia, peak
      expiratory cough flow of reflex cough, and maximum inspiratory and expiratory
      mouth pressures. DISCUSSION: Various novel pharmacologic and nonpharmacologic
      approaches for preventing stroke-associated pneumonia are currently being
      researched. This study investigates a novel strategy based on an exercise
      intervention for cough rehabilitation. TRIAL REGISTRATION: Current Controlled
      Trials ISRCTN40298220.

PMID- 24725278
TI  - 'Be prepared': an implemental mindset for alleviating social-identity threat.
AB  - Stereotype threat occurs when people who belong to socially devalued groups
      experience a fear of negative evaluation, which interferes with the goal of
      staying task focused. The current study was designed to examine whether priming
      socially devalued individuals with an implemental (vs. a deliberative) mindset,
      characterized by forming a priori goal-directed plans, would help these
      individuals to overcome threat-induced distracting states. Participants from low
      and high socioeconomic status backgrounds (measured by maternal education; SESm )
      completed a speeded mental arithmetic test, an intellectually threatening task.
      Low-SESm individuals performed comparably and exhibited similar confidence levels
      to high-SESm counterparts only when induced with an implemental mindset,
      suggesting that implemental mindset priming may help to create equity in the face
      of stereotype threat. 

PMID- 24725279
TI  - 1H NMR diffusion studies of water self-diffusion in supercooled aqueous sodium
      chloride solutions.
AB  - The physical properties of aqueous sodium chloride solutions have been studied
      theoretically, but so far no experimental diffusion data have been obtained under
      supercooled conditions. Here the results of (1)H NMR translational diffusion
      measurements of water in sodium chloride solutions in the temperature range 230
      to 300 K and sodium chloride concentrations up to 4.2 mol/kg are presented. It
      was found that the diffusion data were well-described by the Vogel-Tamman-Fulcher
      relationship with concentration-dependent parameters D0, B, and T0. The results
      indicate that under supercooled conditions the influence of sodium chloride on
      water diffusion is much smaller than predicted by molecular dynamics simulations.

PMID- 24725280
TI  - Obstetric analgesia for vaginal birth in contemporary obstetrics: a survey of the
      practice of obstetricians in Nigeria.
AB  - BACKGROUND: Contemporary obstetrics in sub-Saharan Africa is yet to meet the
      analgesic needs of most women during child birth for a satisfactory birth
      experience and expectedly, obstetricians have a major role to play in achieving
      this. METHODS: This was a questionnaire-based, cross-sectional study of 151
      obstetricians and gynecologists that attended the 46th Annual General Meeting and
      Scientific Conference of the Society of Gynaecology and Obstetrics of Nigeria
      (SOGON) held in Abakaliki, southeast Nigeria in November, 2012. SOGON is the
      umbrella body that oversees the obstetric and gynecological practice in Nigeria.
      Data was collated and analyzed with Epi-info statistical software, and
      conclusions were drawn by means of simple percentages and inferential statistics
      using Odds Ratio, with P-value < 0.05 at 95% Confidence Interval (CI) taken to be
      statistically significant. RESULTS: Of the 151 participants, males predominated;
      110 (72.9%) practiced in government-owned tertiary hospitals in urban locations.
      Only 74 (49%) offered obstetric analgesia. Among users, only 20 (13.3%) offered
      obstetric analgesia routinely to parturients, 44 (29.1%) sometimes and 10 (6.6%)
      on patients' requests. The commonest analgesia was opioids (41.1%). Among non
      users, the commonest reasons adduced were fear of respiratory distress (31.1%),
      cost (24.7%) and late presentation in labour (15.6%). CONCLUSION: The routine
      prescription and utilization of obstetric analgesia by obstetricians in Nigeria
      is still low. Obstetricians are encouraged to step up its use to make childbirth
      a more fulfilling experience for parturients.

PMID- 24725281
TI  - Ectomycorrhizal Cortinarius species participate in enzymatic oxidation of humus
      in northern forest ecosystems.
AB  - In northern forests, belowground sequestration of nitrogen (N) in complex organic
      pools restricts nutrient availability to plants. Oxidative extracellular enzymes
      produced by ectomycorrhizal fungi may aid plant N acquisition by providing access
      to N in macromolecular complexes. We test the hypotheses that ectomycorrhizal
      Cortinarius species produce Mn-dependent peroxidases, and that the activity of
      these enzymes declines at elevated concentrations of inorganic N. In a boreal
      pine forest and a sub-arctic birch forest, Cortinarius DNA was assessed by 454
      sequencing of ITS amplicons and related to Mn-peroxidase activity in humus
      samples with- and without previous N amendment. Transcription of Cortinarius Mn
      peroxidase genes was investigated in field samples. Phylogenetic analyses of
      Cortinarius peroxidase amplicons and genome sequences were performed. We found a
      significant co-localization of high peroxidase activity and DNA from Cortinarius
      species. Peroxidase activity was reduced by high ammonium concentrations.
      Amplification of mRNA sequences indicated transcription of Cortinarius Mn
      peroxidase genes under field conditions. The Cortinarius glaucopus genome encodes
      11 peroxidases - a number comparable to many white-rot wood decomposers. These
      results support the hypothesis that some ectomycorrhizal fungi--Cortinarius
      species in particular--may play an important role in decomposition of complex
      organic matter, linked to their mobilization of organically bound N.

PMID- 24725282
TI  - Premorbid self-disorders and lifetime diagnosis in the schizophrenia spectrum: a
      prospective high-risk study.
AB  - AIM: The notion of a disordered self as a core disturbance of schizophrenia was
      proposed in many foundational texts. Recent studies, spurred by the development
      of the Examination of Anomalous Self-Experience (EASE), seem to indicate that
      self-disorders are a specific manifestation of schizophrenia vulnerability.
      Follow-up studies of help-seeking, prodromal and first-admission patients have
      demonstrated the utility of self-disorders for predicting later schizophrenia
      spectrum disturbance. We wished to extend these findings by gauging the
      predictive value of self-disorders in a premorbid, non-clinical population at
      high risk for schizophrenia. METHODS: Children from the Copenhagen High-Risk
      Project with high-genetic risk for schizophrenia (N = 212) were assessed
      premorbidly (average age = 15), and diagnostically re-evaluated after 10 and 25
      years. Since the EASE was not available at the time of premorbid assessment, we
      hypothesized that a proxy scale drawn from the Minnesota Multiphasic Personality
      Inventory (MMPI) could distinguish those who later developed a schizophrenia
      spectrum disorder (N = 68) from those who remained healthy (N = 64). The Self
      Disorder Scale comprised 32 items whose content suggested an aspect of self
      disorder as measured by the EASE. RESULTS: Premorbid Self-Disorder Scale scores
      significantly predicted lifetime schizophrenia-spectrum diagnosis in the high
      risk cohort. Although there was considerable item overlap between the new scale
      and an existing MMPI scale (psychoticism), the overlap did not account for the
      Self-Disorder Scale's predictive efficacy. CONCLUSION: The results support the
      notion of self-disorders as a core vulnerability feature in schizophrenia,
      detectable premorbidly in those developing later schizophrenia-spectrum
      disorders.

PMID- 24725283
TI  - The creativity and commitment of organ procurement personnel overcome the
      logistical complexities of international organ donations.

PMID- 24725284
TI  - Performance of anesthesia residents during a simulated prone ventricular
      fibrillation arrest in an anesthetized pediatric patient.
AB  - BACKGROUND: Exposure to rare pediatric anesthesia emergencies varies depending on
      the residency program. Simulation can provide increased exposure to these rare
      events, improve performance of residents, and also aid in standardizing the
      curriculum. OBJECTIVE: The purpose of this study was to evaluate time to
      recognize and treat ventricular fibrillation in a pediatric prone patient and to
      expose learners to the difficulties of managing emergencies in prone patients.
      METHODS: Standardized simulation sessions were conducted monthly for 13 months
      with groups of 1-2 residents in each simulation. The scenario involved a prone
      patient undergoing posterior spinal fusion. Ventricular fibrillation occurred
      three minutes into the case. Sessions were viewed by simulation staff, and time
      to events was recorded. A scripted debriefing followed each case. Evaluations
      were completed by each participant. RESULTS: The average time to start chest
      compressions was 77 s, and the average time in recognizing ventricular
      fibrillation was 76 s. No group performed chest compressions while prone. Only
      one group defibrillated in the prone position. Participants average time to
      request defibrillation was 108 s. While nine of 13 groups (69%) ordered an
      arterial blood gas, only five recognized hyperkalemia, and only four groups gave
      calcium. CONCLUSIONS: Anesthesia residents need additional training in
      recognizing and treating operative ventricular fibrillation, especially in prone
      patients and rarely encountered etiologies such as hyperkalemia. Training in the
      treatment of uncommon pediatric emergencies should be a focal point in anesthesia
      residency programs.

PMID- 24725285
TI  - Parkinsonism and severe hypothyroidism in an elderly patient: a case of lithium
      toxicity due to pharmacological interactions.
AB  - WHAT IS KNOWN AND OBJECTIVE: Hypothyroidism is a common clinical side effect of
      lithium treatment, whereas parkinsonism is a very rare adverse event. A number of
      case series of clinical signs of reversible and permanent parkinsonism due to
      lithium toxicity have been previously published, but never in association with
      hypothyroidism. We describe a rare clinical case of concurrent reversible
      parkinsonism and severe hypothyroidism due to lithium toxicity. CASE SUMMARY: The
      patient was a 74-year-old woman chronically treated with carbonate lithium (300
      mg, twice daily) and clomipramine (75 mg, once daily); she also received
      valsartan (160 mg) plus hydrochlorothiazide (12.5 mg), once daily. The patient
      was visited after a 1-week history of progressively worsening and disabling
      parkinsonism. Laboratory tests showed elevated values of lithium and thyroid
      stimulating hormone (TSH) serum concentrations as well as reduced circulating
      thyroid hormone serum concentrations. Lithium treatment was discontinued;
      treatment with levothyroxine and saline solution i.v. was readily performed, and
      valsartan plus hydrochlorothiazide were replaced with amlodipine (5 mg, once
      daily). Within a few days, the patient showed a rapid improvement in overall
      clinical condition, but complete resolution of neurologic symptoms occurred only
      after about 5 months. WHAT IS NEW AND CONCLUSION: Lithium toxicity may present
      with concurrent hypothyroidism and parkinsonism. In the present case, interaction
      with valsartan and hydrochlorothiazide most likely played an important role. In
      patients who receive chronic therapy with lithium, prescribers should monitor
      lithium serum concentration both periodically and immediately at the onset of
      signs and symptoms, potentially related to lithium toxicity.

PMID- 24725286
TI  - Untying chronic pain: prevalence and societal burden of chronic pain stages in
      the general population - a cross-sectional survey.
AB  - BACKGROUND: Chronic pain is a major public health problem. The impact of stages
      of chronic pain adjusted for disease load on societal burden has not been
      assessed in population surveys. METHODS: A cross-sectional survey with 4360
      people aged  >= 14 years representative of the German population was conducted.
      Measures obtained included demographic variables, presence of chronic pain (based
      on the definition of the International Association for the Study of Pain),
      chronic pain stages (by chronic pain grade questionnaire), disease load (by self
      reported comorbidity questionnaire) and societal burden (by self-reported number
      of doctor visits, nights spent in hospital and days of sick leave/disability in
      the previous 12 months, and by current unemployment). Associations between
      chronic pain stages with societal burden, adjusted for demographic variables and
      disease load, were tested by Poisson and logistic regression analyses. RESULTS:
      2508 responses were received. 19.4% (95% CI 16.8% to 22.0%) of participants met
      the criteria of chronic non-disabling non-malignant pain. 7.4% (95% CI 5.0% to
      9.9%) met criteria for chronic disabling non-malignant pain. Compared with no
      chronic pain, the rate ratio (RR) of days with sick leave/disability was 1.6 for
      non-disabling pain and 6.4 for disabling pain. After adjusting for age and
      disease load, the RRs increased to 1.8 and 6.8. The RR of doctor visits was 2.5
      for non-disabling pain and 4.5 for disabling pain if compared with no chronic
      pain. After adjusting for age and disease load, the RR fell to 1.7 and 2.6. The
      RR of days in hospital was 2.7 for non-disabling pain and 11.7 for disabling pain
      if compared with no chronic pain. After adjusting for age and disease load, the
      RR fell to 1.5 and 4.0. Unemployment was predicted by lower educational level
      (Odds Ratio OR 3.27 [95% CI 1.70-6.29]), disabling pain (OR 3.30 [95% CI 1.76
      6.21]) and disease load (OR 1.70 [95% CI 1.41-2.05]). CONCLUSION: Chronic pain
      stages, but also disease load and societal inequalities contributed to societal
      burden. Pain measurements in epidemiology research of chronic pain should include
      chronic pain grades and disease load.

PMID- 24725287
TI  - Preoperative embolization of hypervascular spinal tumors: current practice and
      center experience.
AB  - Preoperative transarterial embolization of hypervascular spinal tumors has been
      extensively used, and is considered to be a highly effective adjuvant technique
      in reducing intraoperative blood loss during surgery. Moreover, it has been
      reported to increase the feasibility and safety of the surgical procedure,
      leading to better surgical outcomes. We review the English literature in an
      attempt to identify indications, appropriate timing of embolization in relation
      to surgery, technical aspects of the procedure, complications, and the
      contribution of embolization to the surgical management of spinal tumors. In
      addition, we report our experience with embolization of hypervascular metastases.

PMID- 24725288
TI  - Spine radiosurgery for spinal metastases: indications, technique and outcome.
AB  - Early diagnosis, better imaging, and advanced treatment of cancer patients extend
      survival and increase the incidence of symptomatic spine metastases. The
      treatment algorithm for spine metastases has shifted to a more aggressive
      approach in recent years. Spine stereotactic radiosurgery (SRS) is a relatively
      new tool utilizing advanced imaging systems, planning software, image-guided
      localization, and intensity-modulated dose delivery. Radiosurgery of spine
      metastases yields high rates of pain- and tumor control, and offers both the
      patients and the treating physicians an effective noninvasive alternative. This
      review presents the indications and outcomes for SRS and describes current
      techniques. 

PMID- 24725289
TI  - En bloc resection of primary tumors of the thoracic spine: indications, planning,
      morbidity.
AB  - OBJECTIVES: We aimed to describe surgical planning, technique, and complications
      of en bloc resection in the thoracic spine in patients who opted for surgery with
      en bloc resection and a tumor-free margin. METHODS: Oncologic and functional
      results were recorded for 134 patients (53% male, age 44 +/- 18 years) who had
      undergone en bloc resection for primary tumors (90 cases) and bone metastases (44
      cases). Patients were followed until death or the latest follow-up examination (0
      211 months, median 47 months). Surgeries were performed from 1990 to 2007 by the
      same team. An ongoing critical analysis of local control rates, surgical
      complications, and expected versus actual loss of function enabled the authors to
      refine the surgical technique and propose seven different types of resection.
      RESULTS AND DISCUSSION: En bloc resection is a demanding procedure and requires
      careful planning after a careful decision-making process. The patient has to
      correctly understand the purpose of the surgery, based on oncological staging, in
      order to accept or decide against the procedure after weighing the possible
      morbidity and functional loss against the expected final result. TECHNIQUES OF EN
      BLOC RESECTION: Seven different strategies to perform en bloc resection in the
      thoracic spine, based on four combinations of surgical approaches (anterior,
      posterior, anterior followed by posterior, and posterior followed by simultaneous
      anterior and posterior) are identified and proposed. This planning is based on
      Weinstein-Boriani-Biagini (WBB) surgical staging. The surgical plan was designed
      to achieve the required oncologic margin with the minimum achievable morbidity.

PMID- 24725290
TI  - Straight from the horse's mouth: neurological injury in equestrian sports.
AB  - OBJECTIVES: Equestrian sports can result in a variety of injuries to the nervous
      system due to many factors. We describe our series of 80 patients with injuries
      sustained during participation in equestrian sports. METHODS AND RESULTS: All
      patients seen at the regional trauma center with injuries associated with
      equestrian sports between 2003 and 2011 were reviewed; 80 patients were
      identified. Fifty-four per cent were female and the average age was 37 years (2.2
      79.3). The mean injury severity score (ISS) was 9.9 +/- 0.7. Only two patients
      had documented helmet use. Glasgow coma score (GCS) was 15 in 93% of patients.
      The most common neurosurgical injuries were to the cranial vault (28%), including
      concussions, intracranial hematomas and hemorrhages, and skull, facial, and spine
      fractures (10%), with the majority (63%) being transverse process fractures. The
      mechanisms of injury varied: 55% were kicked or stepped on, 28% were thrown or
      fell off, and 21% were injured by the horse falling on them. The causes ranged
      from carelessness and lack of attention to animal factors including inadequate
      training of horses and animal fear. Fourteen per cent required surgery. There
      were no mortalities and average length of stay was 3.7 +/- 0.35 days. All
      patients were discharged home with 95% requiring no services. DISCUSSION:
      Equestrian sports convey special risks for its participants. With proper
      protection and precautions, a decrease in the incidence of central nervous system
      injuries may be achieved. Neurosurgeons can play key roles in advocating for
      neurologic safety in equestrian sports.

PMID- 24725291
TI  - Selective cerebral hypothermia induced via hypothermic retrograde jugular vein
      saline flush in a porcine model.
AB  - OBJECTIVES: Multiple methods of selective brain cooling have been used to prevent
      cerebral ischemia secondary to trauma and pathological or iatrogenic cerebral
      blood flow restriction. In this study, we tested the efficacy of hypothermic
      retrograde jugular vein flush (HRJVF) in eliciting selective brain hypothermia in
      a porcine model. METHODS: Twelve swine were divided into two groups: retrograde
      jugular vein infusion (RJVI) with cold saline (4 degrees C RJVI, n  =  6) and
      with room temperature saline (24 degrees C RJVI, n  =  6). For 90 minutes, the
      following parameters were measured: brain parenchymal temperature, rectal
      temperature, intracranial pressure (ICP), mean arterial pressure, and heart rate
      (HR). RESULTS: Swine receiving 4 degrees C RJVI experienced a drop in mean brain
      parenchymal temperature of 1.1 +/- 0.1 degrees C, compared to 0.1 +/- 0.1 degrees
      C in swine receiving 24 degrees C RJVI. At 90 minutes, mean brain parenchymal
      temperature in the 4 degrees C RJVI treatment group was 35.5 +/- 0.2 degrees C,
      as compared to 37.1 +/- 0.2 degrees C in the 24 degrees C RJVI treatment group (P
      < 0.001). In the 4 degrees C RJVI group, the brain-systemic temperature gradient
      peaked 10 minutes after initiation of cooling and remained significantly
      different when comparing the two experimental groups (P < 0.001) throughout the
      duration of the 90 minutes experiment. Of note, ICP, mean arterial pressure, and
      HR remained constant without any significant changes or differences between
      treatment groups. DISCUSSION: These results suggest that HRJVF is an effective
      method for selective brain hypothermia in a large animal model. Clinical
      application may prove effective in delaying neural ischemia.

PMID- 24725292
TI  - Adenosine A2A receptor antagonist istradefylline 20 versus 40 mg/day as
      augmentation for Parkinson's disease: a meta-analysis.
AB  - BACKGROUND: Adenosine A2A receptor antagonist istradefylline 20 mg/day has been
      approved this year for manufacturing and market in Japan. Therefore, we did this
      meta-analysis to systematically evaluate the clinical applicability of 40 mg/day
      as augmentation to levodopa in patients with Parkinson's disease (PD). METHOD:
      Randomized controlled trials (RCT) that compared istradefylline with placebo for
      short-course treatment of PD in adults were systematically reviewed up to
      November 2013. Outcome measurements were daily off time and unified Parkinson's
      disease rating scale (UPDRS) Part III score (on state). Random-effect model was
      used. RESULT: Data were obtained from four RCTs. In these RCTs, 405 patients
      received istradefylline 20 mg/day and 420 patients received 40 mg/day. The pooled
      weighted mean difference was 0.17 with 95% confidence interval (CI)  =  [-0.23,
      0.56] on daily off time and 0.70 with 95% CI  =  [-0.89, 2.29] on UPDRS Part III
      score (on state). The adverse events analysis showed that 20 and 40 mg/day had
      comparable acceptability. Heterogeneity was not existed. CONCLUSION: These
      results indicate that istradefylline 40 mg/day as augmentation shows potential
      promise on clinical applicability, and is worthy of further study. Limited by the
      number of included RCTs, future studies are needed to verify and support this
      conclusion, and assess the long-term effect of istradefylline, the effect of
      istradefylline as monotherapy and other dose of istradefylline.

PMID- 24725293
TI  - Association study of TREM2 polymorphism rs75932628 with late-onset Alzheimer's
      disease in Chinese Han population.
AB  - OBJECTIVE: We conducted a case-control study to investigate whether TREM2
      polymorphism (rs75932628-T) was associated with late onset Alzheimer's disease in
      Chinese Southern Han population. METHODS: PCR-restriction fragment length
      polymorphism assay was performed to genotype rs75932628 in 279 cases with late
      onset Alzheimer's diseases patients and 346 control subjects in Shanghai and
      Nanjing. RESULTS: There was no rs75932628-T variant detected in our sample.
      However, APOEepsilon4 was shown closely associated with the risk of Alzheimer's
      disease (Chi-square = 60.288, P = 0.000). CONCLUSION: Our study suggested that
      TREM2 (rs75932628-T) was rare in Chinese Han population. Further association
      studies with large samples are needed to further study the association of TREM2
      with late-onset Alzheimer's disease.

PMID- 24725294
TI  - A case for international neurosurgical experience: US resident experiences with
      pediatric spinal dysraphism cases.
AB  - INTRODUCTION: In the National Resident Report of Neurological Surgery Case Logs
      prepared by the department of Applications and Data Analysis of the Accreditation
      Council for Graduate Medical Education (ACGME), the Resident Review Committee for
      Neurological Surgery conducted a survey of the total experience of residents
      completing programs in 2008-2011. METHODS: Review of case numbers from the
      Resident Review Committee survey and at an East African hospital with visiting US
      neurosurgical trainees was conducted. RESULTS: US residents reported their
      experiences with the ACGME index cases categorized as 'dysraphism - pediatric
      cases'. The national resident average of pediatric spinal dysraphism cases
      totaled for all years was 8.1 cases with a standard deviation of 11. In contrast,
      more than four spinal dysraphism cases per week were reported per resident during
      a rotation at Kijabe Hospital in Kenya (mean duration of rotation: 2.4 weeks).
      The majority of these cases were myelomeningocele cases. The pediatric
      neurosurgeon in residence at Kijabe has logged over 300 spinal dysraphism cases
      per year since summer of 2010. CONCLUSION: A 4-week international resident
      rotation could potentially provide experience with an average of four spinal
      dysraphism cases per week. Over one month, this could eclipse the 90th percentile
      of US resident experience for an entire residency. This is borne out by
      individual experiences of residents who have visited Kijabe, Kenya, over the past
      several years. The role and value of international neurosurgical experiences for
      residency training can be significant, especially for treatment pathologies
      rarely encountered in many areas of the USA.

PMID- 24725295
TI  - Surface scattering mechanisms of tantalum nitride thin film resistor.
AB  - In this letter, we utilize an electrical analysis method to develop a TaN thin
      film resistor with a stricter spec and near-zero temperature coefficient of
      resistance (TCR) for car-used electronic applications. Simultaneously, we also
      propose a physical mechanism mode to explain the origin of near-zero TCR for the
      TaN thin film resistor (TFR). Through current fitting, the carrier conduction
      mechanism of the TaN TFR changes from hopping to surface scattering and finally
      to ohmic conduction for different TaN TFRs with different TaN microstructures.
      Experimental data of current-voltage measurement under successive increasing
      temperature confirm the conduction mechanism transition. A model of TaN grain
      boundary isolation ability is eventually proposed to influence the carrier
      transport in the TaN thin film resistor, which causes different current
      conduction mechanisms. 

PMID- 24725296
TI  - Complicated grief and suicidality: the impact of subthreshold mood symptoms.
AB  - IntroductionThe aim of the present study was to explore the relationship between
      subthreshold mood symptoms and suicidality in patients with complicated grief
      (CG). METHODS: Fifty patients with CG were included in the study and evaluated by
      the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental
      Disorders, Fourth Edition Axis-I disorders, the Inventory of Complicated Grief,
      and the Mood Spectrum Self Report (MOODS-SR) lifetime version, to evaluate the
      subthreshold mood symptoms. RESULTS: Twenty-eight patients (56%) reported
      lifetime suicidal ideation and 11 patients (22%) reported suicide attempts.
      Subthreshold depressive and rhythmicity/vegetative functions items of the MOODS
      SR were significantly associated with increased suicidal ideation and attempts,
      while subthreshold manic items were associated with suicidal ideation only.
      Relationships were confirmed after controlling for Axis-I disorders comorbidity.
      CONCLUSION: The results of the present study suggest the usefulness of exploring
      lifetime subthreshold mood symptoms in CG patients, in order to promptly identify
      those who may be more prone to suicidality.

PMID- 24725297
TI  - Conceptualizing Treatment Nonadherence in Patients with Bipolar Disorder and
      PTSD.
AB  - Treatment nonadherence is a concern among patients with bipolar disorder and
      posttraumatic stress disorder (PTSD). PTSD is common among patients with bipolar
      disorder and those with this comorbidity often have a more severe course of
      illness. While many factors have been associated with nonadherence in bipolar
      disorder patients and in PTSD patients, almost no research has focused on the
      factors associated with non-adherence in bipolar disorder patients with comorbid
      PTSD. Studies in primary bipolar disorder samples reveal patient, illness, drug
      and clinician characteristics associated with nonadherence while studies in
      primary PTSD samples reveal a significantly shorter list of patient, illness and
      drug characteristics. Shared risk factors between these two populations and the
      characteristics that predict noncompliance in only one population but often
      present in the other, suggest a high likelihood of nonadherence in the bipolar
      disorder-PTSD population. For bipolar disorder-PTSD patients with early childhood
      trauma, noncompliance may be related to the trauma-related meanings attributed to
      interactions with their physicians and their prescribed medications. Given the
      high side effect burden of bipolar disorder treatments and the importance of
      lifelong adherence, clinicians should vigilantly monitor for nonadherence in
      their bipolar disorder-PTSD patients and be particularly aware of patient
      physician psychodynamics that might contribute to this behavior. 

PMID- 24725298
TI  - The mental status exam in talmudic medicine.

PMID- 24725299
TI  - Could Lorazepam be More Effective in Alcohol Withdrawal than Other
      Benzodiazepines?

PMID- 24725300
TI  - The role of information search in seeking alternative treatment for back pain: a
      qualitative analysis.
AB  - BACKGROUND: Health consumers have moved away from a reliance on medical
      practitioner advice to more independent decision processes and so their
      information search processes have subsequently widened. This study examined how
      persons with back pain searched for alternative treatment types and service
      providers. That is, what information do they seek and how; what sources do they
      use and why; and by what means do they search for it? METHODS: 12 persons with
      back pain were interviewed. The method used was convergent interviewing. This
      involved a series of semi-structured questions to obtain open-ended answers. The
      interviewer analysed the responses and refined the questions after each
      interview, to converge on the dominant factors influencing decisions about
      treatment patterns. RESULTS: Persons with back pain mainly search their memories
      and use word of mouth (their doctor and friends) for information about potential
      treatments and service providers. Their search is generally limited due to
      personal, provider-related and information-supply reasons. However, they did want
      in-depth information about the alternative treatments and providers in an attempt
      to establish apriori their efficacy in treating their specific back problems.
      They searched different sources depending on the type of information they
      required. CONCLUSIONS: The findings differ from previous studies about the types
      of information health consumers require when searching for information about
      alternative or mainstream healthcare services. The results have identified for
      the first time that limited information availability was only one of three
      categories of reasons identified about why persons with back pain do not search
      for more information particularly from external non-personal sources.

PMID- 24725302
TI  - Corneal decompensation following bleb needling with 0.01% mitomycin C: a case
      study.

PMID- 24725301
TI  - Knockout of an outer membrane protein operon of Anaplasma marginale by transposon
      mutagenesis.
AB  - BACKGROUND: The large amounts of data generated by genomics, transcriptomics and
      proteomics have increased our understanding of the biology of Anaplasma
      marginale. However, these data have also led to new assumptions that require
      testing, ideally through classical genetic mutation. One example is the
      definition of genes associated with virulence. Here we describe the molecular
      characterization of a red fluorescent and spectinomycin and streptomycin
      resistant A. marginale mutant generated by Himar1 transposon mutagenesis.
      RESULTS: High throughput genome sequencing to determine the Himar1-A. marginale
      genome junctions established that the transposon sequences were integrated within
      the coding region of the omp10 gene. This gene is arranged within an operon with
      AM1225 at the 5' end and with omp9, omp8, omp7 and omp6 arranged in tandem at the
      3' end. RNA analysis to determine the effects of the transposon insertion on the
      expression of omp10 and downstream genes revealed that the Himar1 insertion not
      only reduced the expression of omp10 but also that of downstream genes.
      Transcript expression from omp9, and omp8 dropped by more than 90% in comparison
      with their counterparts in wild-type A. marginale. Immunoblot analysis showed a
      reduction in the production of Omp9 protein in these mutants compared to wild
      type A. marginale. CONCLUSIONS: These results demonstrate that transposon
      mutagenesis in A. marginale is possible and that this technology can be used for
      the creation of insertional gene knockouts that can be evaluated in natural host
      vector systems.

PMID- 24725303
TI  - 'A world of difference': a qualitative study of medical students' views on
      professionalism and the 'good doctor'.
AB  - BACKGROUND: The importance of professional behaviour has been emphasized in
      medical school curricula. However, the lack of consensus on what constitutes
      professionalism poses a challenge to medical educators, who often resort to a
      negative model of assessment based on the identification of unacceptable
      behaviour. This paper presents results from a study exploring medical students'
      views on professionalism, and reports on students' constructs of the 'good' and
      the 'professional' doctor. METHODS: Data for this qualitative study were
      collected through focus groups conducted with medical students from one Western
      Australian university over a period of four years. Students were recruited
      through unit coordinators and invited to participate in a focus group. De
      identified socio-demographic data were obtained through a brief questionnaire.
      Focus groups were audio-recorded, transcribed and subjected to inductive thematic
      analysis. RESULTS: A total of 49 medical students took part in 13 focus groups.
      Differences between students' understandings of the 'good' and 'professional'
      doctor were observed. Being competent, a good communicator and a good teacher
      were the main characteristics of the 'good' doctor. Professionalism was strongly
      associated with the adoption of a professional persona; following a code of
      practice and professional guidelines, and treating others with respect were also
      associated with the 'professional' doctor. CONCLUSIONS: Students felt more
      connected to the notion of the 'good' doctor, and perceived professionalism as an
      external and imposed construct. When both constructs were seen as acting in
      opposition, students tended to forgo professionalism in favour of becoming a
      'good' doctor.Results suggest that the teaching of professionalism should
      incorporate more formal reflection on the complexities of medical practice,
      allowing students and educators to openly explore and articulate any perceived
      tensions between what is formally taught and what is being observed in clinical
      practice.

PMID- 24725304
TI  - Influence of sperm fertilising concentration, sperm selection method and sperm
      capacitation procedure on the incidence of numerical chromosomal abnormalities in
      IVF early bovine embryos.
AB  - The occurrence of numerical chromosomal aberrations, widely described as a major
      cause of mortality in in vitro-produced (IVP) embryos, has been linked to several
      factors. In the present study we investigated the effect of sperm fertilising
      concentration and semen handling (sperm selection and capacitation) before IVF on
      the rate of numerical chromosomal abnormalities in bovine embryos. In all, 466
      IVP cattle embryos were karyotyped throughout three sequential experiments,
      analysing the effects of sperm fertilising concentration (0.1, 1.0 or 10*10(6)
      spermatozoa mL(-1)), selection method (unselected or Percoll-selected
      spermatozoa) and capacitation medium (bovine serum albumin (BSA), heparin or
      their combination). The percentage of normal (diploid) and aberrant (haploid,
      polyploid or aneuploid) embryos was noted in each experiment. The rate of
      numerical chromosomal abnormalities was mainly affected by sperm fertilising
      concentration (P<0.01) and, to a lesser extent, by the sperm capacitation medium
      (P<0.05). Polyploidy and haploidy rates were only affected by sperm fertilising
      concentration (P<0.05). Interestingly, the sperm selection technique used in the
      present study did not reduce the incidence of chromosome abnormalities in IVP
      cattle embryos (P>0.05). Finally, aneuploidy rates were not affected during the
      experiments (P>0.05), which suggests that they are not related to sperm-related
      factors. On the basis of these results, we conclude that sperm fertilising
      concentration is the 'paternal' key factor that affects the rate of numerical
      chromosomal abnormalities in IVP bovine embryos. By making small adjustments to
      fertilising protocols, the rate of cytogenetically aberrant embryos can be
      markedly reduced. 

PMID- 24725305
TI  - Principal components analysis of diet and alternatives for identifying the
      combination of foods that are associated with the risk of disease: a simulation
      study.
AB  - Dietary patterns derived empirically using principal components analysis (PCA)
      are widely employed for investigating diet-disease relationships. In the present
      study, we investigated whether PCA performed better at identifying such
      associations than an analysis of each food on a FFQ separately, referred to here
      as an exhaustive single food analysis (ESFA). Data on diet and disease were
      simulated using real FFQ data and by assuming a number of food intakes in
      combination that were associated with the risk of disease. In each simulation,
      ESFA and PCA were employed to identify the combinations of foods that are
      associated with the risk of disease using logistic regression, allowing for
      multiple testing and adjusting for energy intake. ESFA was also separately
      adjusted for principal components of diet, foods that were significant in the
      unadjusted ESFA and propensity scores. For each method, we investigated the power
      with which an association between diet and disease could be identified, and the
      power and false discovery rate (FDR) for identifying the specific combination of
      food intakes. In some scenarios, ESFA had greater power to detect a diet-disease
      association than PCA. ESFA also typically had a greater power and a lower FDR for
      identifying the combinations of food intakes that are associated with the risk of
      disease. The FDR of both methods increased with increasing sample size, but when
      ESFA was adjusted for foods that were significant in the unadjusted ESFA, FDR
      were controlled at the desired level. These results question the widespread use
      of PCA in nutritional epidemiology. The adjusted ESFA identifies the combinations
      of foods that are causally linked to the risk of disease with low FDR and
      surprisingly good power. 

PMID- 24725306
TI  - A novel species of ellipsoidal multicellular magnetotactic prokaryotes from Lake
      Yuehu in China.
AB  - Two morphotypes of multicellular magnetotactic prokaryotes (MMPs) have been
      identified: spherical (several species) and ellipsoidal (previously one species).
      Here, we report novel ellipsoidal MMPs that are ~ 10 * 8 MUm in size, and
      composed of about 86 cells arranged in six to eight interlaced circles. Each MMP
      was composed of cells that synthesized either bullet-shaped magnetite
      magnetosomes alone, or both bullet-shaped magnetite and rectangular greigite
      magnetosomes. They showed north-seeking magnetotaxis, ping-pong motility and
      negative phototaxis at a velocity up to 300 MUm s(-1) . During reproduction, they
      divided along either their long- or short-body axes. For genetic analysis, we
      sorted the ellipsoidal MMPs with micromanipulation and amplified their genomes
      using multiple displacement amplification. We sequenced the 16S rRNA gene and
      found 6.9% sequence divergence from that of ellipsoidal MMPs, Candidatus
      Magnetananas tsingtaoensis and > 8.3% divergence from those of spherical MMPs.
      Therefore, the novel MMPs belong to different species and genus compared with the
      currently known ellipsoidal and spherical MMPs respectively. The novel MMPs
      display a morphological cell differentiation, implying a potential division of
      labour. These findings provide new insights into the diversity of MMPs in
      general, and contribute to our understanding of the evolution of multicellularity
      among prokaryotes.

PMID- 24725307
TI  - Suboptimal care and maternal mortality among foreign-born women in Sweden:
      maternal death audit with application of the 'migration three delays' model.
AB  - BACKGROUND: Several European countries report differences in risk of maternal
      mortality between immigrants from low- and middle-income countries and host
      country women. The present study identified suboptimal factors related to care
      seeking, accessibility, and quality of care for maternal deaths that occurred in
      Sweden from 1988-2010. METHODS: A subset of maternal death records (n = 75) among
      foreign-born women from low- and middle-income countries and Swedish-born women
      were audited using structured implicit review. One case of foreign-born maternal
      death was matched with two native born Swedish cases of maternal death. An
      assessment protocol was developed that applied both the 'migration three delays'
      framework and a modified version of the Confidential Enquiry from the United
      Kingdom. The main outcomes were major and minor suboptimal factors associated
      with maternal death in this high-income, low-maternal mortality context. RESULTS:
      Major and minor suboptimal factors were associated with a majority of maternal
      deaths and significantly more often to foreign-born women (p = 0.01). The main
      delays to care-seeking were non-compliance among foreign-born women and
      communication barriers, such as incongruent language and suboptimal interpreter
      system or usage. Inadequate care occurred more often among the foreign-born (p =
      0.04), whereas delays in consultation/referral and miscommunication between
      health care providers where equally common between the two groups. CONCLUSIONS:
      Suboptimal care factors, major and minor, were present in more than 2/3 of
      maternal deaths in this high-income setting. Those related to migration were
      associated to miscommunication, lack of professional interpreters, and limited
      knowledge about rare diseases and pregnancy complications. Increased insight into
      a migration perspective is advocated for maternity clinicians who provide care to
      foreign-born women.

PMID- 24725309
TI  - Gary G. Poehling, M.D., editor-in-chief emeritus.

PMID- 24725308
TI  - A remote monitoring and telephone nurse coaching intervention to reduce
      readmissions among patients with heart failure: study protocol for the Better
      Effectiveness After Transition - Heart Failure (BEAT-HF) randomized controlled
      trial.
AB  - BACKGROUND: Heart failure is a prevalent health problem associated with costly
      hospital readmissions. Transitional care programs have been shown to reduce
      readmissions but are costly to implement. Evidence regarding the effectiveness of
      telemonitoring in managing the care of this chronic condition is mixed. The
      objective of this randomized controlled comparative effectiveness study is to
      evaluate the effectiveness of a care transition intervention that includes pre
      discharge education about heart failure and post-discharge telephone nurse
      coaching combined with home telemonitoring of weight, blood pressure, heart rate,
      and symptoms in reducing all-cause 180-day hospital readmissions for older adults
      hospitalized with heart failure. METHODS/DESIGN: A multi-center, randomized
      controlled trial is being conducted at six academic health systems in California.
      A total of 1,500 patients aged 50 years and older will be enrolled during a
      hospitalization for treatment of heart failure. Patients in the intervention
      group will receive intensive patient education using the 'teach-back' method and
      receive instruction in using the telemonitoring equipment. Following hospital
      discharge, they will receive a series of nine scheduled health coaching telephone
      calls over 6 months from nurses located in a centralized call center. The nurses
      also will call patients and patients' physicians in response to alerts generated
      by the telemonitoring system, based on predetermined parameters. The primary
      outcome is readmission for any cause within 180 days. Secondary outcomes include
      30-day readmission, mortality, hospital days, emergency department (ED) visits,
      hospital cost, and health-related quality of life. DISCUSSION: BEAT-HF is one of
      the largest randomized controlled trials of telemonitoring in patients with heart
      failure, and the first explicitly to adapt the care transition approach and
      combine it with remote telemonitoring. The study population also includes
      patients with a wide range of demographic and socioeconomic characteristics. Once
      completed, the study will be a rich resource of information on how best to use
      remote technology in the care management of patients with chronic heart failure.
      TRIAL REGISTRATION: ClinicalTrials.gov # NCT01360203.

PMID- 24725310
TI  - Could the new England journal of medicine be biased against arthroscopic knee
      surgery?

PMID- 24725311
TI  - Concerns over interpretation of data in "anterior cruciate ligament femoral
      footprint anatomy: systematic review of the 21st century literature".

PMID- 24725312
TI  - Anterior cruciate ligament femoral footprint anatomy: systematic review of the
      21st century literature.

PMID- 24725313
TI  - Primary repair of the acetabular labrum: outcomes with 2 years' follow-up.
AB  - PURPOSE: The purpose of this study was to assess the results and outcomes of
      primary repair of the torn acetabular labrum. METHODS: All patients undergoing
      hip arthroscopy are prospectively assessed solely with the modified Harris Hip
      Score, which is an outcomes tool. Over a 4-year period, 37 patients (38 hips)
      underwent primary repair of a torn acetabular labrum and had reached 2 years'
      follow-up. No cases were excluded. For perspective on the frequency of this
      procedure, the ratio of labral refixations after pincer femoroacetabular
      impingement correction to primary repairs was evaluated. RESULTS: The mean age
      was 26 years (range, 11 to 44 years). There were 26 female and 11 male patients,
      with 20 right and 18 left hips. The mean improvement in the modified Harris Hip
      Score was 18.9 points (70.5 points preoperatively and 89.4 points
      postoperatively), with 35 hips (92%) showing improvement, including good and
      excellent results in 35 hips (92%). Associated pathology included articular
      damage (21 hips), ligamentum teres (14 hips), cam femoroacetabular impingement
      (11 hips), borderline dysplasia (center-edge angle, 20 degrees  to 25 degrees )
      (3 hips), dysplasia (center-edge angle <20 degrees ) (2 hips), and iliopsoas (2
      hips). Four patients underwent repeat arthroscopy at a mean of 10 months (range,
      5 to 15 months) postoperatively. The labral repair site was fully healed in each
      of these cases. There were no complications. During the study period, a total of
      1,574 arthroscopic hip procedures were performed, including 439 labral
      refixations, representing an 11.6:1 ratio of refixation to repair. CONCLUSIONS:
      This study showed good clinical results of primary repair with favorable outcomes
      and evidence of good healing, even among the 11% of patients who required repeat
      arthroscopy. LEVEL OF EVIDENCE: Level IV, therapeutic case series.

PMID- 24725314
TI  - Effect of intra-articular local anesthesia on articular cartilage in the knee.
AB  - PURPOSE: To evaluate the hypothetical toxic effect of local anesthetics on the
      articular cartilage using patient data from autologous chondrocyte cultivation
      with different anesthesia types used for arthroscopic cartilage biopsy specimen
      procurement. METHODS: A retrospective analysis of patient data from the national
      autologous chondrocyte implantation registry and the corresponding hospital
      records was approved by the National Medical Ethics Committee. Articular
      cartilage biopsy specimens from the knees of 49 consecutive patients assigned for
      autologous chondrocyte implantation (aged 14 to 44 years) were procured from the
      non-weight-bearing articular surface during arthroscopy under general anesthesia
      (12 patients), spinal anesthesia (18 patients), or local anesthesia (intra
      articular injection of 15 to 20 mL of 2% lidocaine hydrochloride) (19 patients).
      All the biopsy specimens were further manipulated following the same chondrocyte
      cultivation protocol. General patient data and surgery-related parameters,
      together with chondrocyte viability, population doublings, and chondrocyte
      morphology in biopsy specimens and primary cell cultures, were analyzed and
      compared across different types of anesthesia. RESULTS: Patients in the general,
      spinal, and local anesthesia groups showed no statistical differences in age (27
      years, 29 years, and 32 years, respectively), duration of surgery (36 minutes, 37
      minutes, and 39 minutes, respectively), weight of biopsy specimens (110 mg, 178
      mg, and 130 mg, respectively), cell viability in cartilage biopsy specimens (67%,
      69%, and 78%, respectively) or primary cultures (95%, 95%, and 95%,
      respectively), and population doublings (5.2, 5.2, and 5.2, respectively).
      Similar chondrocyte morphology in primary cell cultures was observed among the 3
      groups. CONCLUSIONS: This retrospective study showed that a single intra
      articular injection of lidocaine hydrochloride used for knee arthroscopy did not
      influence the viability, morphology, and cultivation potential of chondrocytes in
      articular cartilage biopsy specimens assigned for autologous chondrocyte
      implantation. LEVEL OF EVIDENCE: Level IV, retrospective comparative study.

PMID- 24725315
TI  - The knee arthroscopy learning curve: quantitative assessment of surgical skills.
AB  - PURPOSE: To assess orthopaedic trainees performing diagnostic knee arthroscopies
      and evaluate procedural competence using a novel statistical method, the
      Cumulative Summation Test for Learning Curve (LC-CUSUM). METHODS: Twenty
      orthopaedic trainees in postgraduate year (PGY) 1 through 5 performed diagnostic
      knee arthroscopy and were evaluated intraoperatively with a validated 10-point
      knee task-specific checklist (TSCL) and 50-point global rating scale (GRS). A
      score of 40 points or greater (of 50 points) for the GRS and 8 points or greater
      (of 10 points) for the knee TSCL was considered to indicate a successful
      procedure. For the LC-CUSUM analysis, adequate performance was defined as a 10%
      failure rate, inadequate performance was defined as a 30% failure rate, and an
      acceptable deviation from adequate performance was defined as 10%. A limit h
      equal to 1.6 was selected to give a true-discovery rate of 90% and a false
      discovery rate of 10% over 50 procedures. RESULTS: A total of 340 consecutive
      procedures were performed by 20 trainees during the 12-month study period. The
      cumulative number of arthroscopic procedures performed by trainees before study
      start increased with increasing PGY. The median number of arthroscopic procedures
      performed per trainee was 16.5 (interquartile range, 14 to 21.75). Competency in
      knee arthroscopy for the TSCL was achieved by 8 trainees (40%), after a median of
      16 procedures (interquartile range, 13 to 20), and for the GRS by only a single
      trainee (5%), after 14 procedures. Threshold-adjusted curves stratified by PGY
      level enabled multiple trainees to achieve competency for both the TSCL and GRS.
      CONCLUSIONS: The LC-CUSUM can be successfully applied to knee arthroscopy to
      provide an individualized assessment of performance and quantitatively
      demonstrate competency for basic arthroscopic tasks. CLINICAL RELEVANCE: The LC
      CUSUM is an effective method to evaluate procedure competence in arthroscopic
      training and can provide objective feedback and benchmarks in the learning phase.

PMID- 24725316
TI  - Endoscopic-assisted achilles tendon reconstruction with free hamstring tendon
      autograft for chronic rupture of achilles tendon: clinical and isokinetic
      evaluation.
AB  - PURPOSE: To evaluate the clinical and functional outcome of endoscopic-assisted
      reconstruction of chronic ruptures of the Achilles tendon using free hamstring
      tendon autograft. METHODS: We present a case series of 15 patients who had
      chronic ruptures of the Achilles tendon (>6 weeks earlier) and underwent
      endoscopic-assisted reconstruction with a free hamstring autograft. The graft
      loop was passed through and fixed to the proximal stump of the tendon. The graft
      was then passed through suture to the distal stump and finally inserted into a
      tunnel in the anterior calcaneus to the Achilles tendon insertion and fixed with
      an bioabsorbable interference screw. The mean follow-up period was 27 months (SD,
      3 months; range, 24 to 33 months). All patients underwent magnetic resonance
      imaging preoperatively, immediately postoperatively, and at follow-up 2 years
      postoperatively. All patients were functionally evaluated with the American
      Orthopaedic Foot & Ankle Society (AOFAS) score for the hindfoot preoperatively
      and postoperatively. Calf muscle power was evaluated by isokinetic strength
      testing at 2 years' follow-up. RESULTS: The mean size of the gap on preoperative
      magnetic resonance imaging was 49 mm (SD, 9 mm). The mean preoperative AOFAS
      score was 32.6 (SD, 7.5). There was a statistically significant improvement in
      the postoperative AOFAS score after 2 years to 90.8 (SD, 3.54) (P < .05). The
      mean time of return to all daily activities (except running and other sports) was
      12.6 weeks (SD, 1.39 weeks). Isokinetic testing showed a nonsignificant deficit
      (<10%) between the involved and uninvolved plantar flexors and dorsiflexors with
      regard to peak torque, average power, and total work. CONCLUSIONS: Endoscopic
      assisted Achilles tendon reconstruction with free hamstring tendon autograft for
      chronic ruptures of the Achilles tendon showed good to excellent results in all
      patients. Isokinetic testing showed a nonsignificant deficit between the involved
      and uninvolved sides at 2 years' follow-up. LEVEL OF EVIDENCE: Level IV,
      therapeutic cases series.

PMID- 24725317
TI  - Characterization and comparison of 5 platelet-rich plasma preparations in a
      single-donor model.
AB  - PURPOSE: The purpose of this study was to compare the biological characteristics
      of platelet-rich plasma (PRP) obtained from 4 medical devices and a preparation
      developed in our laboratory using a single-donor model. METHODS: Ten healthy
      persons donated blood that was processed to produce PRP by use of 4 commercial
      preparation systems and a protocol developed in our laboratory. Volumes and
      platelet, white blood cell (WBC), and red blood cell concentrations were
      recorded. The platelet activation status was assessed by flow cytometry. Enzyme
      linked immunosorbent assay was used to determine the concentrations of vascular
      endothelial growth factor, platelet-derived growth factor AB, epidermal growth
      factor, and transforming growth factor beta1. We calculated platelet capture
      efficiency, relative composition, and increase factors from whole blood in
      platelets and WBC, as well as platelet and growth factor (GF) doses, provided
      from each preparation. RESULTS: Leukocyte-rich PRP was obtained with RegenPRP
      (RegenLab, Le Mont-sur-Lausanne, Switzerland) and the Mini GPS III System (Biomet
      Biology, Warsaw, IN) and provides PRP with higher proportions of red blood cells,
      WBCs, and neutrophils than leukocyte-poor PRP obtained with the Selphyl System
      (Selphyl, Bethlehem, PA), Arthrex ACP (Arthrex, Naples, FL), and the preparation
      developed in our laboratory. The highest platelet and GF concentrations and doses
      were obtained with the Mini GPS III System and the preparation developed in our
      laboratory. Different centrifugation protocols did not show differences in the
      percentages of activated platelets. Finally, a positive correlation between
      platelet doses and all the GFs studied was found, whereas a positive correlation
      between WBC doses and GFs was found only for vascular endothelial growth factor
      and epidermal growth factor. CONCLUSIONS: In a single-donor model, significant
      biological variations in PRP obtained from different preparation systems were
      highlighted. The observed differences suggest different results for treated
      tissue and could explain the large variability in the clinical benefit of PRP
      reported in the literature. CLINICAL RELEVANCE: Our findings will help clinicians
      to choose a system that meets their specific needs for a given indication.

PMID- 24725318
TI  - Effects of potassium and sodium supply on drought-adaptive mechanisms in
      Eucalyptus grandis plantations.
AB  - A basic understanding of nutrition effects on the mechanisms involved in tree
      response to drought is essential under a future drier climate. A large-scale
      throughfall exclusion experiment was set up in Brazil to gain an insight into the
      effects of potassium (K) and sodium (Na) nutrition on tree structural and
      physiological adjustments to water deficit. Regardless of the water supply, K and
      Na supply greatly increased growth and leaf area index (LAI) of Eucalyptus
      grandis trees over the first 3 yr after planting. Excluding 37% of throughfall
      reduced above-ground biomass accumulation in the third year after planting for K-
      supplied trees only. E. grandis trees were scarcely sensitive to drought as a
      result of the utilization of water stored in deep soil layers after clear-cutting
      the previous plantation. Trees coped with water restriction through stomatal
      closure (isohydrodynamic behavior), osmotic adjustment and decrease in LAI.
      Additionally, droughted trees showed higher phloem sap sugar concentrations. K
      and Na supply increased maximum stomatal conductance, and the high water
      requirements of fertilized trees increased water stress during dry periods.
      Fertilization regimes should be revisited in a future drier climate in order to
      find the right balance between improving tree growth and limiting water shortage.

PMID- 24725319
TI  - Pro.voc.a.tive: causing discussion, thought, argument, etc.

PMID- 24725320
TI  - Creation of the terms epithelium and endothelium.

PMID- 24725322
TI  - Fluorescein-tear breakup time as an assessment of efficacy of tear replacement
      therapy in dry eye patients: a systematic review and meta-analysis.
AB  - PURPOSE: To review outcomes of studies where fluorescein-tear breakup time
      (fTBUT) measurements had been made before and after treatment with artificial
      tears. METHODS: Peer-reviewed articles were identified that reported average
      values for fTBUT before and after approximately 1 month of treatment of dry eye
      with aqueous-based artificial tears. 48 data sets were used for calculating the
      net (percentage) change in fTBUT, with 21 including information of variability
      (as reported SD of average value) of the fTBUT data suitable for a meta-analysis.
      RESULTS: Prior to treatment, average fTBUT values ranged from 0.9 s to 11.8 s
      (group mean 4.7 +/- 1.7 s, n = 48 data sets). After treatment, these values
      ranged from 2.2 to 10.7 s (group mean 6.1 +/- 2.3 s; P<.001), with net increase
      for the treatment effect being 1.4 +/- 1.2 s (range - 1.4 to + 4.5 s). Similar
      changes were reported regardless of the type of product type. The meta-analysis
      confirmed a net effect at 1.3 s, with the magnitude of the variability (as a
      weighted SE) having a similar overall value of 1.1 s. CONCLUSIONS: Following use
      of 'artificial tears' by dry eye patients, a small but predictable increase in
      tear film stability has generally been reported, the net magnitude of which is
      close to a 33% improvement.

PMID- 24725323
TI  - Surgical management of pterygium.
AB  - Pterygia are noncancerous growths of conjunctiva that may require surgical
      removal because of discomfort, cosmesis, or obstruction of vision. Pterygia often
      recur after excision. The major goal of pterygium treatment is avoiding
      recurrence, but complication rates and cosmetic results are also considered.
      Despite the number of techniques available, there is no consensus on the best
      procedure. Even the best techniques carry risk of recurrence and complications.
      In this review, different surgical techniques, graft attachment methods, and
      adjuvant therapies in current use are discussed. Also discussed are newer
      techniques that early studies have shown to be promising, but require more
      investigation before becoming a recommended treatment. The review is intended to
      provide an overview of the current research to inform surgeons with regard to
      their decisions and aid researchers in hypothesis generation. 

PMID- 24725321
TI  - The chemokine receptor CCR7 expressed by dendritic cells: a key player in corneal
      and ocular surface inflammation.
AB  - Dendritic cells (DCs) are highly potent stimulators of the immune system, and
      their contribution as such to the pathogenesis of corneal and ocular surface
      inflammatory disease has been well established. These vigorous antigen-presenting
      cells are reliant upon their effective migration from peripheral tissues (e.g.,
      those of the ocular surface) to the lymphoid organs, where immune responses are
      triggered and can then cause disease. The chemokine receptor CCR7 expressed on
      DCs has emerged as the master mediator of this highly complex migratory process,
      and thus it is important in causing corneal and ocular surface inflammation.
      Furthermore, CCR7 has received considerable attention as a potential therapeutic
      target, as topically instilled antagonists of this receptor are quite effective
      therapeutically in a mouse model of ocular allergy. These findings and more are
      reviewed in the current article. In addition, the understanding regarding CCR7
      function in mice and humans, and the biology of DCs that populate the ocular
      surface are also detailed herein. The involvement of DCs and their expression of
      CCR7 in corneal and ocular surface diseases such as in ocular allergy, dry eye
      disease, immune rejection and more, are also reviewed here. 

PMID- 24725324
TI  - SeventhInternational Conference on the Tear Film & Ocular Surface: Basic Science
      and Clinical Relevance (Taormina, Sicily, September 2013). Highlights from the
      platform sessions.

PMID- 24725325
TI  - Irritable eye syndrome: neuroimmune mechanisms and benefits of selected
      nutrients.
AB  - Previous studies showed comorbidity of some ocular, enteral, and affective
      symptoms comprising irritable eye syndrome. Aims of the present study were to
      learn more about the pathogenic mechanisms of this syndrome and to evaluate
      benefits of food supplements on these disorders. In in vitro assay, Lactobacillus
      acidophilus lysate inhibited interleukin (IL)-1beta and tumor necrosis factor
      (TNF)-alpha generation of lipopolysaccharide (LPS)-stimulated macrophages in dose
      and size-dependent manner. For a prospective, open-label phase I/II controlled
      clinical trial, 40 subjects affected by ocular dysesthesia and hyperesthesia and
      comorbid enteral and anxiety-depression symptoms were randomly assigned either
      into the treated group, which received a composition containing probiotic lysate,
      vitamins A, B, and D and omega 3 fatty acids, or into the control group, which
      received vitamins and omega 3 fatty acids. For reference, 20 age- and sex-matched
      healthy subjects were also selected. White blood count (WBC) and lymphocyte and
      monocyte counts, as well as IL-6 and TNF-alpha levels, were significantly above
      the reference levels in both treated and control groups. After 8 weeks, WBC and
      lymphocyte and monocyte counts, and cytokine levels significantly decreased, and
      ocular, enteral, and anxiety-depression symptoms significantly improved in the
      treated group as compared to the control group. This proof-of-concept study
      suggested that subclinical inflammation may be a common mechanism connecting
      ocular, enteral, and anxiety/depression symptoms, and supplements affecting
      dysbiosis may be a new approach to treating this syndrome.

PMID- 24725326
TI  - Evaluation of an automated thermodynamic treatment (LipiFlow(r)) system for
      meibomian gland dysfunction: a prospective, randomized, observer-masked trial.
AB  - PURPOSE: To compare the effectiveness of a single LipiFlow((r)) treatment with
      combined lid warming and massage in patients with meibomian gland dysfunction
      (MGD). METHODS: In this prospective, randomized, crossover, observer-masked
      clinical trial, subjects were randomized to receive either a single 12-min
      LipiFlow-LipiFlow Thermal Pulsation (LTP) system treatment or to perform combined
      twice-daily lid warming and massage for 3 months. All subjects were examined
      before, and 1 and 3 months after initiation of treatments. Investigated
      parameters included subjective symptoms, lipid layer thickness, meibomian gland
      assessment, tear break-up time, tear osmolarity, corneal and conjunctival
      staining, Schirmer test values, and tear meniscus height. RESULTS: A total of 31
      subjects completed the 3-month follow-up. At 1 and 3 months, patients in the
      LipiFlow treatment group had a significant reduction in Ocular Surface Disease
      Index (OSDI) scores compared with those in the lid-margin hygiene group. Both
      treatments produced a significant improvement in expressible meibomian glands
      compared to the baseline parameters, but no significant difference was noted
      between the two groups. The other investigated objective parameters did not show
      a significant difference. CONCLUSION: Results of our study show that a single
      LipiFlow treatment is as least as effective as a 3-month, twice-daily lid margin
      hygiene regimen for MGD. However, the present study was observer-masked only, and
      therefore a placebo effect may have confounded any improvements in subjective
      symptoms and other parameters in both groups.

PMID- 24725327
TI  - Some are more equal than others.

PMID- 24725328
TI  - An assessment of the educational value of service-learning community placements
      in residential aged care facilities.
AB  - AIMS: The aim of this study was to determine whether dental hygiene students
      attending residential aged care facilities (RACFs) during a placement programme
      gained any knowledge about the oral care of elderly patients and the RACF
      environment. LOCATION: Aged Care Facilities on the Central Coast of New South
      Wales, Australia. METHODOLOGY: Final year dental hygiene students undertook a 12
      week placement, one day per week, in one of 17 residential aged care facilities
      on the NSW Central Coast. They were asked to complete pre-placement and post
      placement questionnaires, which recorded their knowledge of medical, dental and
      environmental issues related to older people. The placement questionnaires used
      five point Likert scales, ranging from strongly agree to strongly disagree, pre-
      and post-mean scores were produced for each question and P values calculated
      using a paired t-test. RESULTS: Thirty-three students attended the placement, 26
      (79%) completed both the pre- and post-placement questionnaires. Post-placement
      mean scores as compared to pre-placement mean scores showed significant
      improvement in student knowledge of medical (P < 0.05) and dental (P < 0.05)
      conditions specific to the older person and improvement in knowledge (P < 0.05)
      about the residential aged care facility environment. CONCLUSION: The placement
      programme enhanced student knowledge across three subject categories; medical and
      dental conditions of the older person and the structure and services of the
      residential aged care environment.

PMID- 24725329
TI  - Family-focused therapy for individuals at clinical high risk for psychosis:
      treatment fidelity within a multisite randomized trial.
AB  - AIM: Family psychoeducation is an effective adjunct to pharmacotherapy in
      delaying relapse among patients with schizophrenia and bipolar disorder. This
      study tested the treatment adherence and competence of newly trained clinicians
      to an adaptation of family-focused therapy for individuals at clinical high risk
      for psychosis (FFT-CHR). METHODS: The sample included 103 youth or young adults
      (ages 12-30 years) who had attenuated positive symptoms of psychosis. Families
      participated in a randomized trial comparing two psychosocial interventions: FFT
      CHR (18 sessions over 6 months) and enhanced care (EC; 3 sessions over 1 month).
      Following a 1.5-day training seminar, 24 clinicians from eight study sites
      received teleconference supervision in both treatment protocols for the 2-year
      study period. Treatment fidelity was rated with the 13-item Therapy Competence
      and Adherence Scales, Revised. RESULTS: Supervisors classified 90% of treatment
      sessions as above acceptable fidelity thresholds (ratings of 5 or better on a 1-7
      scale of overall fidelity). As expected, fidelity ratings indicated that FFT-CHR
      included a greater emphasis on communication and problem-solving skills training
      than EC, but ratings of non-specific clinician skills, such as maintaining
      rapport and appropriately pacing sessions, did not differ between conditions.
      Treatment fidelity was not related to the severity of symptoms or family conflict
      at study entry. CONCLUSIONS: FFT-CHR can be administered with high levels of
      fidelity by clinicians who receive training and supervision. Future studies
      should examine whether there are more cost-effective methods for training,
      supervising and monitoring the fidelity of FFT-CHR.

PMID- 24725330
TI  - Enhanced optical confinement and lasing characteristics of individual urchin-like
      ZnO microstructures prepared by oxidation of metallic Zn.
AB  - We prepared urchin-like micron-sized ZnO cavities with high optical quality by
      oxidizing metallic Zn and proposed the mechanism that resulted in the growth of
      the urchin-like microstructures. The photoluminescence spectra of the ZnO
      microstructures had a predominant excitonic emission at room temperature. The
      lasing properties of the urchin-like ZnO microstructures were investigated
      systematically through excitation power- and size-dependent photoluminescence
      measurements. The results showed that a low lasing threshold with high quality
      factors could be achieved because of the high reflectivity of the optical
      reflectors formed by the tapered nanowires. The unique optical characteristics
      may facilitate the development of high-efficiency random lasers. 

PMID- 24725331
TI  - Chronic treatment with anesthetic propofol attenuates beta-amyloid protein levels
      in brain tissues of aged mice.
AB  - Alzheimer's disease (AD) is the most common form of dementia. At the present
      time, however, AD still lacks effective treatments. Our recent studies showed
      that chronic treatment with anesthetic propofol attenuated brain caspase-3
      activation and improved cognitive function in aged mice. Accumulation of beta
      amyloid protein (Abeta) is a major component of the neuropathogenesis of AD
      dementia and cognitive impairment. We therefore set out to determine the effects
      of chronic treatment with propofol on Abeta levels in brain tissues of aged mice.
      Propofol (50 mg/kg) was administrated to aged (18 month-old) wild-type mice once
      a week for 8 weeks. The brain tissues of mice were harvested one day after the
      final propofol treatment. The harvested brain tissues were then subjected to
      enzyme-linked immunosorbent assay (ELISA) and Western blot analysis. Here we
      report that the propofol treatment reduced Abeta (Abeta40 and Abeta42) levels in
      the brain tissues of the aged mice. Moreover, the propofol treatment decreased
      the levels of beta-site amyloid precursor protein cleaving enzyme (the enzyme for
      Abeta generation), and increased the levels of neprilysin (the enzyme for Abeta
      degradation) in the brain tissues of the aged mice. These results suggested that
      the chronic treatment with propofol might reduce brain Abeta levels potentially
      via decreasing brain levels of beta-site amyloid precursor protein cleaving
      enzyme, thus decreasing Abeta generation; and via increasing brain neprilysin
      levels, thus increasing Abeta degradation. These preliminary findings from our
      pilot studies have established a system and postulated a new hypothesis for
      future research. 

PMID- 24725332
TI  - Work ability of Chinese migrant workers: the influence of migration
      characteristics.
AB  - BACKGROUND: Migrant workers have become a vital labor supply to China's economy.
      Their migration process and work conditions may influence their health and work
      ability. The work ability of migrant workers in China and the influence of the
      migration process on work ability have not been explored extensively in previous
      studies. The objective of this study is to evaluate the association of migration
      characteristics and work-related factors with work ability among migrant workers
      in the Pearl River Delta. METHODS: In this cross-sectional survey, the study
      population consisted of 907 migrant workers from ten factories in the Pearl River
      Delta who were exposed to organic solvents during work. The primary dependent
      variable of the study was work ability, measured by the Work Ability Index (WAI).
      The independent variables were individual characteristics, migration
      characteristics, and work-related factors. Logistic regression models were used
      to determine the influence of different factors on work ability and three
      dimensions of WAI. RESULTS: The result shows that among migration
      characteristics, social support was significantly associated with all three
      dimensions of the work ability index. Permanent migration intention and longer
      length of migration were negatively associated with the mental resource dimension
      of WAI. WAI was also influenced by individual and work-related factors.
      CONCLUSIONS: The findings of this study suggest that expanding migrants' social
      networks and social support systems in their work place or living community,
      (i.e. expanding the functions of labor unions) would be an effective way to
      improve migrant workers' work ability. Improving of migrant workers' physical and
      psychosocial related work environments would also increase their work ability.

PMID- 24725333
TI  - Risk groups in children under six months of age using self-organizing maps.
AB  - Fetal and infant growth tends to follow irregular patterns and, particularly in
      developing countries, these patterns are greatly influenced by unfavorable living
      conditions and interactions with complications during pregnancy. The aim of this
      study was to identify groups of children with different risk profiles for growth
      development. The study sample comprised 496 girls and 508 boys under six months
      of age from 27 pediatric primary health care units in the city of Rio de Janeiro,
      Brazil. Data were obtained through interviews with the mothers and by reviewing
      each child's health card. An unsupervised learning, know as a self-organizing map
      (SOM) and a K-means algorithm were used for cluster analysis to identify groups
      of children. Four groups of infants were identified. The first (139) consisted of
      infants born exclusively by cesarean delivery, and their mothers were exclusively
      multiparous; the highest prevalences of prematurity and low birthweight, a high
      prevalence of exclusive breastfeeding and a low proportion of hospitalization
      were observed for this group. The second (247 infants) and the third (298
      infants) groups had the best and worst perinatal and infant health indicators,
      respectively. The infants of the fourth group (318) were born heavier, had a low
      prevalence of exclusive breastfeeding, and had a higher rate of hospitalization.
      Using a SOM, it was possible to identify children with common features, although
      no differences between groups were found with respect to the adequacy of
      postnatal weight. Pregnant women and children with characteristics similar to
      those of group 3 require early intervention and more attention in public policy. 

PMID- 24725334
TI  - The miRNAome of the postpartum dairy cow liver in negative energy balance.
AB  - BACKGROUND: Negative energy balance (NEB) is an altered metabolic state in high
      yielding cows that occurs during the first few weeks postpartum when energy
      demands for lactation and maintenance exceed the energy supply from dietary
      intake. NEB can, in turn, lead to metabolic disorders and to reduced fertility.
      Alterations in the expression of more than 700 hepatic genes have previously been
      reported in a study of NEB in postpartum dairy cows. miRNAs (microRNA) are known
      to mediate many alterations in gene expression post transcriptionally. To study
      the hepatic miRNA content of postpartum dairy cows, including their overall
      abundance and differential expression, in mild NEB (MNEB) and severe NEB (SNEB),
      short read RNA sequencing was carried out. To identify putative targets of
      differentially expressed miRNAs among differentially expressed hepatic genes
      reported previously in dairy cows in SNEB computational target identification was
      employed. RESULTS: Our results indicate that the dairy cow liver expresses 53
      miRNAs at a lower threshold of 10 reads per million. Of these, 10 miRNAs
      accounted for greater than 95% of the miRNAome (miRNA content). Of the highly
      expressed miRNAs, miR-122 constitutes 75% followed by miR-192 and miR-3596. Five
      out of thirteen let-7 miRNA family members are also among the highly expressed
      miRNAs. miR-143, down-regulated in SNEB, was found to have 4 putative up
      regulated gene targets associated with SNEB including LRP2 (low density
      lipoprotein receptor-related protein 2), involved in lipid metabolism and up
      regulated in SNEB. CONCLUSIONS: This is the first liver miRNA-seq profiling study
      of moderate yielding dairy cows in the early postpartum period. Tissue specific
      miR-122 and liver enriched miR-192 are two of the most abundant miRNAs in the
      postpartum dairy cow liver. miR-143 is significantly down-regulated in SNEB and
      putative targets of miRNA-143 which are up-regulated in SNEB, include a gene
      involved in lipid metabolism.

PMID- 24725335
TI  - Risk factors for brain metastases in locally advanced non-small cell lung cancer
      with definitive chest radiation.
AB  - PURPOSE: We intended to identify risk factors that affect brain metastases (BM)
      in patients with locally advanced non-small cell lung cancer (LA-NSCLC) receiving
      definitive radiation therapy, which may guide the choice of selective prevention
      strategies. METHODS AND MATERIALS: The characteristics of 346 patients with stage
      III NSCLC treated with thoracic radiation therapy from January 2008 to December
      2010 in our institution were retrospectively reviewed. BM rates were analyzed by
      the Kaplan-Meier method. Multivariate Cox regression analysis was performed to
      determine independent risk factors for BM. RESULTS: The median follow-up time was
      48.3 months in surviving patients. A total of 74 patients (21.4%) experienced BM
      at the time of analysis, and for 40 (11.7%) of them, the brain was the first site
      of failure. The 1-year and 3-year brain metastasis rates were 15% and 28.1%,
      respectively. In univariate analysis, female sex, age <=60 years, non-squamous
      cell carcinoma, T3-4, N3, >3 areas of lymph node metastasis, high lactate
      dehydrogenase and serum levels of tumor markers (CEA, NSE, CA125) before
      treatment were significantly associated with BM (P<.05). In multivariate
      analysis, age <=60 years (P=.004, hazard ratio [HR] = 0.491), non-squamous cell
      carcinoma (P=.000, HR=3.726), NSE >18 ng/mL (P=.008, HR=1.968) and CA125 >= 35
      U/mL (P=.002, HR=2.129) were independent risk factors for BM. For patients with
      0, 1, 2, and 3 to 4 risk factors, the 3-year BM rates were 7.3%, 18.9%, 35.8%,
      and 70.3%, respectively (P<.001). CONCLUSIONS: Age <=60 years, non-squamous cell
      carcinoma, serum NSE >18 ng/mL, and CA125 >= 35 U/mL were independent risk
      factors for brain metastasis. The possibilities of selectively using prophylactic
      cranial irradiation in higher-risk patients with LA-NSCLC should be further
      explored in the future.

PMID- 24725336
TI  - Facilitating the transition from physiology to hospital wards through an
      interdisciplinary case study of septic shock.
AB  - BACKGROUND: In order to develop clinical reasoning, medical students must be able
      to integrate knowledge across traditional subject boundaries and multiple
      disciplines. At least two dimensions of integration have been identified:
      horizontal integration, bringing together different disciplines in considering a
      topic; and vertical integration, bridging basic science and clinical practice.
      Much attention has been focused on curriculum overhauls, but our approach is to
      facilitate horizontal and vertical integration on a smaller scale through an
      interdisciplinary case study discussion and then to assess its utility. METHODS:
      An interdisciplinary case study discussion about a critically ill patient was
      implemented at the end of an organ system-based, basic sciences module at New
      York University School of Medicine. Three clinical specialists-a cardiologist, a
      pulmonologist, and a nephrologist-jointly led a discussion about a complex
      patient in the intensive care unit with multiple medical problems secondary to
      septic shock. The discussion emphasized the physiologic underpinnings behind the
      patient's presentation and the physiologic considerations across the various
      systems in determining proper treatment. The discussion also highlighted the
      interdependence between the cardiovascular, respiratory, and renal systems, which
      were initially presented in separate units. After the session students were given
      a brief, anonymous three-question free-response questionnaire in which they were
      asked to evaluate and freely comment on the exercise. RESULTS: Students not only
      took away physiological principles but also gained an appreciation for various
      thematic lessons for bringing basic science to the bedside, especially horizontal
      and vertical integration. The response of the participants was overwhelmingly
      positive with many indicating that the exercise integrated the material across
      organ systems, and strengthened their appreciation of the role of physiology in
      understanding disease presentations and guiding appropriate therapy. CONCLUSIONS:
      Horizontal and vertical integration can be presented effectively through a single
      session case study, with complex patient cases involving multiple organ systems
      providing students opportunities to integrate their knowledge across organ
      systems while emphasizing the importance of physiology in clinical reasoning.
      Furthermore, having several clinicians from different specialties discuss the
      case together can reinforce the matter of integration across multiple organ
      systems and disciplines in students' minds.

PMID- 24725337
TI  - Prostate-specific antigen flare induced by cabazitaxel-based chemotherapy in
      patients with metastatic castration-resistant prostate cancer.
AB  - BACKGROUND: A prostate-specific antigen (PSA) flare occurs in about 15% of
      metastatic castration-resistant prostate cancer (mCRPC) patients receiving
      docetaxel. This flare has no standard definition. Its impact on treatment
      efficacy is unclear. We sought to evaluate the incidence and characteristics of
      PSA flare on cabazitaxel, and its impact on survival. METHODS: Multicentre
      retrospective review of consecutive patients treated with cabazitaxel second-line
      chemotherapy for mCRPC. Collection of baseline characteristics, disease history
      and PSA levels before and during cabazitaxel therapy. Overall survival (OS) and
      radiological/clinical progression-free survival (PFS) for patient groups
      corresponding to different definitions of PSA flare estimated by the Kaplan-Meier
      method and compared using the log-rank test. RESULTS: Overall, 125 patients were
      included. Median PFS and OS were 6.5 and 13.3 months, respectively. Depending
      upon the definition used, flare incidence ranged from 8.3% to 30.6%. The flare
      lasted <2.6 months. A PSA flare followed by a ? 50% decrease was associated with
      a median PFS and OS of 11.2 and 25.2 months, respectively. Median PFS and OS for
      a ? 30% rather than ? 5 0% decrease were 10.4 and 16.5 months. These outcomes
      were not significantly different from those in patients with immediate PSA
      decreases of ? 50% or ? 30% from baseline, but were significantly better than in
      patients experiencing no PSA decrease (p = 0.006 and 0.015, respectively, for
      OS). CONCLUSION: The PSA response to cabazitaxel, with or without initial flare,
      was associated with a strong survival benefit. The taxane-induced flare during
      the first 12 weeks of therapy can be ignored when evaluating PSA response.

PMID- 24725339
TI  - Focus on Women's Mental Health.

PMID- 24725338
TI  - Valproic acid triggers increased mitochondrial biogenesis in POLG-deficient
      fibroblasts.
AB  - Valproic acid (VPA) is a widely used antiepileptic drug and also prescribed to
      treat migraine, chronic headache and bipolar disorder. Although it is usually
      well tolerated, a severe hepatotoxic reaction has been repeatedly reported after
      VPA administration. A profound toxic reaction on administration of VPA has been
      observed in several patients carrying POLG mutations, and heterozygous genetic
      variation in POLG has been strongly associated with VPA-induced liver toxicity.
      Here we studied the effect of VPA in fibroblasts of five patients carrying
      pathogenic mutations in the POLG gene. VPA administration caused a significant
      increase in the expression of POLG and several regulators of mitochondrial
      biogenesis. It was further supported by elevated mtDNA copy numbers. The effect
      of VPA on mitochondrial biogenesis was observed in both control and patient cell
      lines, but the capacity of mutant POLG to increase the expression of
      mitochondrial genes and to increase mtDNA copy numbers was less effective. No
      evidence of substantive differences in DNA methylation across the genome was
      observed between POLG mutated patients and controls. Given the marked
      perturbation of gene expression observed in the cell lines studied, we conclude
      that altered DNA methylation is unlikely to make a major contribution to POLG
      mediated VPA toxicity. Our data provide experimental evidence that VPA triggers
      increased mitochondrial biogenesis by altering the expression of several
      mitochondrial genes; however, the capacity of POLG-deficient liver cells to
      address the increased metabolic rate caused by VPA administration is
      significantly impaired. 

PMID- 24725340
TI  - Psychiatric comorbidity in women with chronic pelvic pain.
AB  - Chronic pain syndromes are often treatment refractory and pose an enormous burden
      of suffering for the individual. Chronic pelvic pain (CPP) is generally defined
      as noncyclic pain of at least 6 months duration and severe enough to require
      medical care or cause disability. CPP has been estimated to have a prevalence of
      15% among women of reproductive age. Women are at increased risk for both major
      depression and chronic pain syndromes such as CPP, and are more likely to report
      antecedent stressful events, have higher rates of physical and sexual abuse, and
      subsequently develop posttraumatic stress disorder. High rates of sexual and
      physical abuse and other trauma have been shown among women with CPP, including
      symptoms of dyspareunia (pain during intercourse), dysmenorrhea (pain during
      menstruation), and vulvar pain. A detailed and comprehensive evaluation of the
      patient with CPP should include a thorough gynecologic exam and a full mental
      health assessment. Treatment of CPP must include an integrated approach targeted
      at both the psychiatric comorbidity and pain symptoms. A multidisciplinary
      treatment team offers the best chance for success with CPP, and it is critical to
      suggest psychiatric treatment (psychopharmacology and/or psychotherapy) in
      addition to traditional medical and surgical approaches. 

PMID- 24725341
TI  - Women and substance abuse: health considerations and recommendations.
AB  - There has been growing evidence in recent years of the importance of gender
      specific issues in the addiction field. This paper explores specific problems and
      including specific health consequences faced by women who drink or use drugs. We
      describe helpful screening tools that can be used in the primary care setting and
      offer an understanding of some of the barriers preventing women from seeking
      help. This article also provides guidance on the best pharmacotherapy and
      psychological interventions that can be used to help women recover from their
      addiction. 

PMID- 24725342
TI  - Female sexual disorders: assessment, diagnosis, and treatment.
AB  - Sexual health is important to overall health and quality of life. Sexual problems
      have been associated with relationship problems and may interfere with overall
      health and they may also be a marker for other undiagnosed comorbid medical
      conditions. In order for healthcare professionals to manage the sexual health
      concerns of their patients, it is important for them to understand what
      constitutes good sexual health. To that end, it is necessary to have a working
      knowledge of the evolving theoretical models offered to describe a healthy sexual
      response as well as an understanding of the neurobiology of sexual function. The
      Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Revised
      lists six primary female sexual disorders: hypoactive sexual desire disorder,
      sexual aversion disorder, female sexual arousal disorder, female orgasmic
      disorder,dyspareunia, and vaginismus. Despite a growing awareness of the high
      prevalence of sexual disorders they are not typically identified nor treated.
      There are a number of reasons why clinicians fail to identify and treat sexual
      problems including insufficient training in sexual medicine and communication
      skills, time-constraints, and embarrassment. Treatment for female sexual problems
      is usually individualized and may include a combination of office-based education
      and basic counseling, cognitive-behavioral psychotherapy, pharmacotherapy, and
      treatment of concomitant medical conditions. 

PMID- 24725343
TI  - Facial subcutaneous emphysema after tonsillectomy.
AB  - BACKGROUND: Tonsillectomy is a commonly performed and relatively safe surgical
      procedure. However, it can potentially be associated with several complications.
      We report a case of facial subcutaneous emphysema that occurred after elective
      tonsillectomy. CASE: Tonsillectomy was performed on a patient with a history of
      frequent tonsillitis. After surgery, the patient developed facial subcutaneous
      emphysema that resolved within a few days without any further complications.
      CONCLUSION: Subcutaneous emphysema is a rare complication of tonsillectomy.
      Tonsil should be removed along the tonsilar capsule. If its removal causes a
      deeper than usual mucosal tear up to the level of the muscles, then air might
      potentially pass through the pharyngeal wall to the parapharyngeal,
      retropharyngeal and prevertebral spaces.

PMID- 24725344
TI  - Effect of hypoxia on the expression of alphaB-crystallin in head and neck
      squamous cell carcinoma.
AB  - BACKGROUND: The presence of hypoxia in head and neck squamous cell carcinoma
      (HNSCC) is associated with therapeutic resistance and increased risk of
      metastasis formation. alphaB-crystallin (HspB5) is a small heat shock protein,
      which is also associated with metastasis formation in HNSCC. In this study, we
      investigated whether alphaB-crystallin protein expression is increased in hypoxic
      areas of HNSCC biopsies and analyzed whether hypoxia induces alphaB-crystallin
      expression in vitro and in this way may confer hypoxic cell survival. METHODS: In
      38 HNSCC biopsies, the overlap between immunohistochemically stained alphaB
      crystallin and pimonidazole-adducts (hypoxiamarker) was determined. Moreover,
      expression levels of alphaB-crystallin were analyzed in HNSCC cell lines under
      hypoxia and reoxygenation conditions and after exposure to reactive oxygen
      species (ROS) and the ROS scavenger N-acetylcysteine (NAC). siRNA-mediated
      knockdown was used to determine the influence of alphaB-crystallin on cell
      survival under hypoxic conditions. RESULTS: In all biopsies alphaB-crystallin was
      more abundantly present in hypoxic areas than in normoxic areas. Remarkably,
      hypoxia decreased alphaB-crystallin mRNA expression in the HNSCC cell lines. Only
      after reoxygenation, a condition that stimulates ROS formation, alphaB-crystallin
      expression was increased. alphaB-crystallin mRNA levels were also increased by
      extracellular ROS, and NAC abolished the reoxygenation-induced alphaB-crystallin
      upregulation. Moreover, it was found that decreased alphaB-crystallin levels
      reduced cell survival under hypoxic conditions. CONCLUSIONS: We provide the first
      evidence that hypoxia stimulates upregulation of alphaB-crystallin in HNSCC. This
      upregulation was not caused by the low oxygen pressure, but more likely by ROS
      formation. The higher expression of alphaB-crystallin may lead to prolonged
      survival of these cells under hypoxic conditions.

PMID- 24725345
TI  - Differential cellular uptake and metabolism of curcuminoids in
      monocytes/macrophages: regulatory effects on lipid accumulation.
AB  - We have previously shown that curcumin (CUR) may increase lipid accumulation in
      cultured human acute monocytic leukaemia cell line THP-1 monocytes/macrophages,
      but that tetrahydrocurcumin (THC), an in vivo metabolite of CUR, has no such
      effect. In the present study, we hypothesised that the different cellular uptake
      and/or metabolism of CUR and THC might be a possible explanation for the
      previously observed differences in their effects on lipid accumulation in THP-1
      monocytes/macrophages. Chromatography with tandem MS revealed that CUR was
      readily taken up by THP-1 monocytes/macrophages and slowly metabolised to
      hexahydrocurcumin sulphate. By contrast, the uptake of THC was low. In parallel
      with CUR uptake, increased lipid uptake was observed in THP-1 macrophages but not
      with the uptake of THC or another CUR metabolite and structurally related
      compounds. From these results, it is possible to deduce that CUR and THC are
      taken up and metabolised differently in THP-1 cells, which determine their
      biological activity. The remarkable differential cellular uptake of CUR, relative
      to THC and other similar molecules, may imply that the CUR uptake into cells may
      occur via a transporter. 

PMID- 24725346
TI  - Water addition regulates the metabolic activity of ammonia oxidizers responding
      to environmental perturbations in dry subhumid ecosystems.
AB  - Terrestrial arid and semi-arid ecosystems (drylands) constitute about 41% of the
      Earth's land surface and are predicted to experience increasing fluctuations in
      water and nitrogen availability. Mounting evidence has confirmed the significant
      importance of ammonia-oxidizing archaea (AOA) and bacteria (AOB) in
      nitrification, plant nitrogen availability and atmospheric N2 O emissions, but
      their responses to environmental perturbations in drylands remain largely
      unknown. Here we evaluate how the factorial combinations of irrigation and
      fertilization in forests and land-use change from grassland to forest affects the
      dynamics of AOA and AOB following a 6-year dryland field study. Potential
      nitrification rates and AOA and AOB abundances were significantly higher in the
      irrigated plots, accompanied by considerable changes in community compositions,
      but their responses to fertilization alone were not significant. DNA-stable
      isotope probing results showed increased (13) CO2 incorporation into the amoA
      gene of AOA, but not of AOB, in plots receiving water addition, coupled with
      significantly higher net mineralization and nitrification rates. High-throughput
      microarray analysis revealed that active AOA assemblages belonging to
      Nitrosopumilus and Nitrosotalea were increasingly labelled by (13) CO2 following
      irrigation. However, no obvious effects of land-use changes on nitrification
      rates or metabolic activity of AOA and AOB could be observed under dry
      conditions. We provide evidence that water addition had more important roles than
      nitrogen fertilization in influencing the autotrophic nitrification in dryland
      ecosystems, and AOA are increasingly involved in ammonia oxidation when dry soils
      become wetted. 

PMID- 24725347
TI  - Oligomer-targeting with a conformational antibody fragment promotes toxicity in
      Abeta-expressing flies.
AB  - INTRODUCTION: The self-assembly of Abeta peptides into a range of
      conformationally heterogeneous amyloid states represents a fundamental event in
      Alzheimer's disease. Within these structures oligomeric intermediates are
      considered to be particularly pathogenic. To test this hypothesis we have used a
      conformational targeting approach where particular conformational states, such as
      oligomers or fibrils, are recognized in vivo by state-specific antibody
      fragments. RESULTS: We show that oligomer targeting with the KW1 antibody
      fragment, but not fibril targeting with the B10 antibody fragment, affects
      toxicity in Abeta-expressing Drosophila melanogaster. The effect of KW1 is
      observed to occur selectively with flies expressing Abeta(1-40) and not with
      those expressing Abeta(1-42) or the arctic variant of Abeta(1-42) This finding is
      consistent with the binding preference of KW1 for Abeta(1-40) oligomers that has
      been established in vitro. Strikingly, and in contrast to the previously
      demonstrated in vitro ability of this antibody fragment to block oligomeric
      toxicity in long-term potentiation measurements, KW1 promotes toxicity in the
      flies rather than preventing it. This result shows the crucial importance of the
      environment in determining the influence of antibody binding on the nature and
      consequences of the protein misfolding and aggregation. CONCLUSIONS: While our
      data support to the pathological relevance of oligomers, they highlight the
      issues to be addressed when developing inhibitory strategies that aim to
      neutralize these states by means of antagonistic binding agents.

PMID- 24725348
TI  - Proteomic comparison of Ralstonia solanacearum strains reveals temperature
      dependent virulence factors.
AB  - BACKGROUND: Ralstonia solanacearum, the causal agent of bacterial wilt, is a
      genetically diverse bacterial plant pathogen present in tropical and subtropical
      regions of the world that infects more than 200 plant species, including
      economically important solanaceous crops. Most strains of R. solanacearum are
      only pathogenic at temperatures between 25 to 30 degrees C with strains that can
      cause disease below 20 degrees C considered a threat to agriculture in temperate
      areas. Identifying key molecular factors that distinguish strains virulent at
      cold temperatures from ones that are not is needed to develop effective
      management tools for this pathogen. We compared protein profiles of two strains
      virulent at low temperature and two strains not virulent at low temperature when
      incubated in the rhizosphere of tomato seedlings at 30 and 18 degrees C using
      quantitative 2D DIGE gel methods. Spot intensities were quantified and compared,
      and differentially expressed proteins were sequenced and identified by mass
      spectrometry (MS/MS). RESULTS: Four hundred and eighteen (418) differentially
      expressed protein spots sequenced produced 101 unique proteins. The identified
      proteins were classified in the Gene Ontology biological processes categories of
      metabolism, cell processes, stress response, transport, secretion, motility, and
      virulence. Identified virulence factors included catalase (KatE), exoglucanase A
      (ChbA), drug efflux pump, and twitching motility porin (PilQ). Other proteins
      identified included two components of a putative type VI secretion system. We
      confirmed differential expression of 13 candidate genes using real time PCR
      techniques. Global regulators HrpB and HrpG also had temperature dependent
      expression when quantified by real time PCR. CONCLUSIONS: The putative
      involvement of the identified proteins in virulence at low temperature is
      discussed. The discovery of a functional type VI secretion system provides a new
      potential virulence mechanism to explore. The global regulators HrpG and HrpB,
      and the protein expression profiles identified suggest that virulence at low
      temperatures can be partially explained by differences in regulation of virulence
      factors present in all the strains.

PMID- 24725349
TI  - Efficacy of orthopedic treatment with protraction facemask on skeletal Class III
      malocclusion: a systematic review and meta-analysis.
AB  - The objective of this systematic review was to estimate the efficacy of
      protraction facemask on the correction of Class III malocclusion in the short
      term. A systematic review of articles was performed using different electronic
      databases (PubMed, Ovid, Cochrane Central Register of Controlled Trials, Web of
      Science, LILACS, and Google Scholar). Search terms comprised 'orthopedic
      treatment' and 'Class III malocclusion'. The selection criteria were set in order
      to include in this review only randomized clinical trials (RCTs) performed
      treating with facemask Class III growing patients. Studies' selection, data
      extraction, and risk of bias's assessment were executed independently by two
      authors using pre-defined data forms. All pooled analyses of data were based on
      random effects models. A pre-specified subgroup analysis was planned to evaluate
      the effect of preliminary rapid palatal expansion on facemask efficacy. Three
      RCTs met our inclusion criteria. In total, data from 155 patients (92 treated and
      63 controls) were collected. The treated group showed the following significant
      changes: ANB degrees  +3.66 degrees  [95%CI (2.58, 4.74)]; SNA degrees  +2.10
      [95%CI (1.14, 3.06)]; SNB degrees  -1.54 [95%CI (-2.13, -0.95)]; SN-palatal plane
      -0.82 degrees  [95%CI (-1.62, -0.02)]; and SN-mandibular plane +1.51 [95%CI
      (0.61, 2.41)]. Heterogeneity varied from low to moderate (mean I(2) value: 41.4
      +/- 20.8). Facemask is effective correcting Class III malocclusion in the short
      term. The skeletal modifications induced by facemask are forward displacement of
      maxilla, backward displacement of mandible, clockwise rotation of the mandibular
      plane, and counterclockwise rotation of the maxillary plane. 

PMID- 24725350
TI  - Acquired microcephaly in blepharophimosis-ptosis-epicanthus inversus syndrome
      because of an interstitial 3q22.3q23 deletion.
AB  - BACKGROUND: Blepharophimosis-ptosis-epicanthus inversus syndrome is an autosomal
      dominant condition because of mutations or deletions of the FOXL2 gene.
      Microcephaly is not associated with FOXL2 mutations but has been reported in
      individuals with chromosome 3q deletions, which include the FOXL2 gene and other
      contiguous genes. The ATR gene has been reported as a candidate gene for
      microcephaly in individuals with contiguous deletion of chromosome 3q involving
      the FOXL2 gene. PATIENT: We describe a girl with blepharophimosis-ptosis
      epicanthus inversus syndrome along with acquired microcephaly and intellectual
      disability. RESULTS: Our patient had a deletion of chromosome 3q22.2q23, which
      does not include the ATR gene but does include the PIK3CB gene as a candidate
      gene for microcephaly. CONCLUSION: We propose that the PIK3CB gene included in
      our patient's chromosome 3q deletion may be the gene responsible for microcephaly
      and other patients with blepharophimosis-ptosis-epicanthus inversus syndrome
      because of a chromosome 3q deletion.

PMID- 24725351
TI  - Idiopathic bilateral carpal tunnel syndrome in a 9-month-old infant presenting as
      a pseudo-dystonia.
AB  - BACKGROUND: Carpal tunnel syndrome is the most common focal peripheral neuropathy
      seen in most electrophysiological laboratories. Although the incidence of carpal
      tunnel syndrome in adults is 50 to 150 cases per 100,000 people, it is rare in
      children. There are less than 200 case reports of carpal tunnel syndrome in
      children, with mucopolysaccharides and mucolipidosis being the most frequent
      cause. Idiopathic carpal tunnel syndrome with childhood onset occurs in less than
      0.2% of cases. PATIENT: We describe a 9-month-old infant who presented with
      intermittent abnormal posturing movement of both hands. RESULTS: The clinical
      presentation and the electrophysiological studies confirmed the diagnosis of
      carpal tunnel syndrome. His dystonic posturing had disappeared completely 3 weeks
      after surgical release of both flexor retinaculi. CONCLUSION: We are not only
      reporting the youngest child with carpal tunnel syndrome, but we also report a
      new cause of abnormal movement disorder in children.

PMID- 24725352
TI  - Time-dependent pH sensing phenomena using CdSe/ZnS quantum dots in EIS structure.
AB  - Time-dependent pH sensing phenomena of the core-shell CdSe/ZnS quantum dot (QD)
      sensors in EIS (electrolyte insulator semiconductor) structure have been
      investigated for the first time. The quantum dots are immobilized by chaperonin
      GroEL protein, which are observed by both atomic force microscope and scanning
      electron microscope. The diameter of one QD is approximately 6.5 nm. The QDs are
      not oxidized over a long time and core-shell CdSe/ZnS are confirmed by X-ray
      photon spectroscopy. The sensors are studied for sensing of hydrogen ions
      concentration in different buffer solutions at broad pH range of 2 to 12. The QD
      sensors show improved sensitivity (38 to 55 mV/pH) as compared to bare SiO2
      sensor (36 to 23 mV/pH) with time period of 0 to 24 months, owing to the
      reduction of defects in the QDs. Therefore, the differential sensitivity of the
      QD sensors with respect to the bare SiO2 sensors is improved from 2 to 32 mV/pH
      for the time period of 0 to 24 months. After 24 months, the sensitivity of the QD
      sensors is close to ideal Nernstian response with good linearity of 99.96%.
      Stability and repeatability of the QD sensors show low drift (10 mV for 10
      cycles) as well as small hysteresis characteristics (<10 mV). This QD sensor is
      very useful for future human disease diagnostics. 

PMID- 24725353
TI  - PORT (Programme of Recognition and Therapy): the first Polish recognition and
      treatment programme for patients with an at-risk mental state.
AB  - AIM: To present the activities of the first early intervention centre in Poland
      and the Programme of Recognition and Therapy (PORT) run by the centre. METHODS:
      An overview of the admission process, diagnostic procedures and therapeutic
      interventions offered to individuals with an at-risk mental state. RESULTS: The
      PORT programme, developed in 2010, included 81 individuals, aged 15-29 years so
      far. The diagnostic procedures consists of evaluation of symptoms with the use of
      the Comprehensive Assessment of At-Risk Mental State (CAARMS), assessment of
      premorbid and current personality traits and the evaluation of cognitive
      functions. Therapeutic interventions include cognitive behavioural therapy, diet
      supplementation with omega-3 fatty acids and pharmacological treatment. Overall
      rate of conversion into psychosis within the years 2010-2103 was 18.5%. The
      programme has also been a source of research in the field of early psychosis.
      CONCLUSIONS: The PORT programme enables young people with an ARMS an easy access
      to the specialized service offering treatment tailored to their specific needs.

PMID- 24725354
TI  - Hemodialysis for infants, children, and adolescents.
AB  - Children with chronic kidney disease stage 5 requiring dialysis can be treated by
      peritoneal or hemodialysis. In the United Kingdom nearly twice as many children
      receive peritoneal dialysis compared with hemodialysis. Technical aspects of
      pediatric hemodialysis are challenging and include the relative size of
      extracorporeal circuit and child's blood volume, assessment of adequacy,technical
      and complications of vascular access. Alternatives to standard hospital-based
      hemodialysis are also increasingly available. Optimizing nutritional status with
      the support of specialist pediatric dietitians is key to the management of
      children receiving hemodialysis. The effects of chronic illness on growth and
      school achievement, as well as the psychological, emotional, and social
      development of the child should not be underestimated. This review focuses on the
      above elements and highlights common pediatric practice in the United Kingdom. 

PMID- 24725355
TI  - Efficacy of a combined contraceptive regimen consisting of condoms and emergency
      contraception pills.
AB  - BACKGROUND: To evaluate and compare the effectiveness of the combined regimen
      (consisting of condoms and emergency contraception pills (ECP)) and using condoms
      only for the purpose of preventing pregnancy. METHODS: One-thousand-five-hundred
      and-sixty-two (1,562) couples as volunteers enrolled at nine centers in Shanghai.
      Eight-hundred-and-twelve (812) were randomized to use male condoms and ECP (i.e.,
      Levonorgestrel) as a back-up to condoms (the intervention group) and 750 to use
      male condoms only(the control group), according to their working unit.
      Participants were visited at admission and at the end of 1, 3, 6, 9, and 12
      months. The cumulative life table rates were calculated for pregnancy and other
      reasons for discontinuation. RESULT: The gross cumulative life table rates showed
      that the cumulative discontinuation rates for all reasons during the year of
      follow-up in the condoms plus emergency contraception group and the condoms only
      group were 7.76 +/- 0.94 and 6.61 +/- 0.91, respectively, per 100 women (chi2 =
      0.41, p = 0.5227). The cumulative gross pregnancy rate of the condoms plus
      emergency contraception group and the condoms only group were 2.17 +/- 0.52 and
      1.25 +/- 0.41, respectively, per 100 women (chi2 = 1.93, p = 0.1645). The Pearl
      Index in the condoms plus emergency contraception group and the condoms only
      group were 2.21% and 1.26%, respectively. CONCLUSION: Male condoms remain a
      highly effective contraceptive method for a period of one year while consistently
      and correctly used. In addition, the lowest pregnancy rate followed from perfect
      use condom.

PMID- 24725356
TI  - Does the perception of fairness and standard of care in the health system depend
      on the field of study? Results of an empirical analysis.
AB  - BACKGROUND: The main challenge in the context of health care reforms and priority
      setting is the establishment and/or maintenance of fairness and standard of care.
      For the political process and interdisciplinary discussion, the subjective
      perception of the health care system might even be as important as potential
      objective criteria. Of special interest are the perceptions of academic
      disciplines, whose representatives act as decision makers in the health care
      sector. The aim of this study is to explore and compare the subjective perception
      of fairness and standard of care in the German health care system among students
      of medicine, law, economics, philosophy, and religion. METHODS: Between October
      2011 and January 2012, we asked freshmen and advanced students of the fields
      mentioned above to participate in a paper and pencil survey. Prior to this, we
      formulated hypotheses. The data were analysed by micro econometric regression
      techniques. RESULTS: Data from 1,088 students were included in the study. Medical
      students, freshmen, and advanced students perceive the standard of care
      significantly as being better than non-medical students. Differences in the
      perception of fairness are not significant between the freshmen of the academic
      disciplines; however, they increase with the number of study terms. Besides the
      field of study, further variables such as gender and health status have a
      significant impact on perceptions. CONCLUSIONS: Our results show that there are
      differences in the perception of fairness and standard of care between academic
      disciplines, which might influence the interdisciplinary discussion on health
      care reforms and priority setting.

PMID- 24725357
TI  - Attitudes toward borderline personality disorder: a survey of 706 mental health
      clinicians.
AB  - OBJECTIVE: We sought to determine attitudes toward patients with borderline
      personality disorder (BPD) among mental health clinicians at nine academic
      centers in the United States. METHODS: A self-report questionnaire was
      distributed to 706 mental health clinicians, including psychiatrists, psychiatry
      residents, social workers, nurses, and psychologists. RESULTS: The study showed
      that most clinicians consider BPD a valid diagnosis, although nearly half
      reported that they preferred to avoid these patients. The clinician's
      occupational subgroup was significantly related to attitude. Staff nurses had the
      lowest self-ratings on overall caring attitudes, while social workers had the
      highest. Social workers and psychiatrists had the highest ratings on treatment
      optimism. Social workers and psychologists were most optimistic about
      psychotherapy effectiveness, while psychiatrists were most optimistic about
      medication effectiveness. Staff nurses had the lowest self-ratings on empathy
      toward patients with BPD and treatment optimism.DiscussionNegative attitudes
      persist among clinicians toward BPD, but differ among occupational subgroups.
      Overall, caring attitudes, empathy, and treatment optimism were all higher among
      care providers who had cared for a greater number of BPD patients in the past 12
      months. CONCLUSION: These findings hold important implications for clinician
      education and coordination of care for patients with BPD.

PMID- 24725358
TI  - Self-harm in prisoners.
AB  - IntroductionSelf-harm is a direct, socially unacceptable,repetitive behavior that
      causes minor to moderate physical injury without suicidal intent. It is also a
      significant and growing concern among prison inmates, although it has been rarely
      studied. In the present study, we aimed to investigate demographic, psychosocial,
      and clinical variables associated to this critical bahaviour in a high risk
      sample of 1,555 male prisoners. METHODS: Prisoners were interviewed about their
      history of self-mutilation, psychiatric history,and forensic history. The
      prisoners completed the Barratt Impulsivity Scale, Buss-Durkee Hostility
      Inventory, Eysenck Personality Questionnaire, and Childhood Trauma Questionnaire.
      RESULTS: Eighteen percent of prisoners had a history of self-harm. They more
      frequently reported childhood traumas, were more likely to be unmarried,
      previously imprisoned, tested positive for substance abuse, had a history of
      suicide attempt, and more likely showed violent tendencies.DiscussionSelf-harm
      among prisoners is common, being found in almost 20% of the subjects in our
      sample. Self-mutilation among prisoners appears to be multi-factorial with
      developmental, socio-demographic, psychiatric, and personality determinants.
      CONCLUSION: Self-harm is associated with critical behaviors such as violence,
      substance abuse and suicide attempts, which represent major critical problems in
      contention environments.

PMID- 24725359
TI  - Hypersalivation associated with olanzapine and valproate combination: a case
      report.

PMID- 24725360
TI  - The expression of Dicer and Drosha in matched normal tissues, tumours and lymph
      node metastases in triple negative breast cancer.
AB  - BACKGROUND: Breast cancer is the most common malignancy in women world-wide.
      Triple negative breast cancer (TNBC) is a highly aggressive subtype that lacks
      expression of hormone receptors for estrogen, progesterone and human epidermal
      growth factor 2; and is associated with a high propensity for metastatic spread.
      Several studies have identified critical roles for microRNAs in breast cancer,
      but the role of two critical enzymes involved in microRNA biogenesis, Dicer and
      Drosha, is not well understood, particularly with respect to metastatic
      progression in this subtype. METHODS: We examined the expression of Dicer and
      Drosha in a series of invasive 35 TNBCs with matched normal adjacent tissues (n =
      18) and lymph node metastases (n = 15) using semi-quantitative real time RT-PCR.
      The relationship of their expression with clinical features including age at
      diagnosis, lymph node positivity and tumour size was analysed. RESULTS: We report
      that Dicer was significantly decreased while Drosha was significantly increased
      in tumours when compared to normal adjacent tissues. While there was no
      difference in Drosha expression in lymph node metastases when compared to the
      primary tumour, Dicer was significantly increased. There was no correlation
      between the expression of either Dicer or Drosha to age at diagnosis, lymph node
      positivity and tumour size. CONCLUSIONS: In conclusion, Dicer and Drosha are
      dysregulated in TNBC and matched lymph node metastases however, the clinical
      relevance of this is still not known. The altered expression of Dicer and Drosha
      may serve as markers for disrupted miRNA biogenesis in TNBC.

PMID- 24725361
TI  - Tracking the dispersion of Scaphoideus titanus Ball (Hemiptera: Cicadellidae)
      from wild to cultivated grapevine: use of a novel mark-capture technique.
AB  - The dispersion of Scaphoideus titanus Ball adults from wild to cultivated
      grapevines was studied using a novel mark-capture technique. The crowns of wild
      grapevines located at a distance from vineyards ranging from 5 to 330 m were
      sprayed with a water solution of either cow milk (marker: casein) or chicken egg
      whites (marker: albumin) and insects captured in yellow sticky traps placed on
      the canopy of grapes were analyzed via an indirect ELISA for markers'
      identification. Data were subject to exponential regression as a function of
      distance from wild grapevine, and to spatial interpolation (Inverse Distance
      Weighted and Kernel interpolation with barriers) using ArcGIS Desktop 10.1
      software. The influence of rainfall and time elapsed after marking on markers'
      effectiveness, and the different dispersion of males and females were studied
      with regression analyses. Of a total of 5417 insects analyzed, 43% were positive
      to egg; whereas 18% of 536 tested resulted marked with milk. No influence of
      rainfall or time elapsed was observed for egg, whereas milk was affected by time.
      Males and females showed no difference in dispersal. Marked adults decreased
      exponentially along with distance from wild grapevine and up to 80% of them were
      captured within 30 m. However, there was evidence of long-range dispersal up to
      330 m. The interpolation maps showed a clear clustering of marked S. titanus
      close to the treated wild grapevine, and the pathways to the vineyards did not
      always seem to go along straight lines but mainly along ecological corridors. S.
      titanus adults are therefore capable of dispersing from wild to cultivated
      grapevine, and this may affect pest management strategies.

PMID- 24725362
TI  - Spatial distribution analyses of natural phyllosphere-colonizing bacteria on
      Arabidopsis thaliana revealed by fluorescence in situ hybridization.
AB  - Bacterial colonizers of the aerial parts of plants, or phyllosphere, have been
      identified on a number of different plants using cultivation-dependent and
      independent methods. However, the spatial distribution at the micrometer scale of
      different main phylogenetic lineages is not well documented and mostly based on
      fluorescence-tagged model strains. In this study, we developed and applied a
      spatial explicit approach that allowed the use of fluorescence in situ
      hybridization (FISH) to study bacterial phylloplane communities of
      environmentally grown Arabidopsis thaliana. We found on average 5.4 * 10(6)
      bacteria cm(-2) leaf surface and 1.5 * 10(8) bacteria g(-1) fresh weight.
      Furthermore, we found that the total biomass in the phylloplane was normally
      distributed. About 31% of the bacteria found in the phylloplane did not hybridize
      to FISH probes but exhibited infrared autofluorescence indicative for aerobic
      anoxygenic phototrophs. Four sets of FISH probes targeting Alphaproteobacteria,
      Betaproteobacteria, Actinobacteria and Bacteroidetes were sufficient to identify
      all other major contributors of the phylloplane community based on general
      bacterial probing. Spatial aggregation patterns were observed for all probe
      targeted populations at distances up to 7 MUm, with stronger tendencies to co
      aggregate for members of the same phylogenetic group. Our findings contribute to
      a bottom-up description of leaf surface community composition.

PMID- 24725363
TI  - Inconsistent condom use among Ugandan university students from a gender
      perspective: a cross-sectional study.
AB  - BACKGROUND: Feminization of the HIV/AIDS epidemic has been a prominent phenomenon
      in sub-Saharan Africa. Inconsistent condom use among young people is one of the
      major risk factors in the continued propagation of the epidemic. Therefore, it is
      of importance to increase knowledge of gender aspects of condom use among young
      people. OBJECTIVE: To investigate whether gender differences regarding individual
      and social factors determine the association between condom efficacy and
      inconsistent condom use with a new sex partner, among Ugandan university
      students. DESIGN: In 2010, 1954 Ugandan students participated in a cross
      sectional survey, conducted at Mbarara University of Science and Technology in
      southwestern Uganda. A self-administered questionnaire assessed socio-demographic
      factors, alcohol consumption, sexual behaviors (including condom use and condom
      efficacy), and peer norms. The data were stratified by sex and examined by
      multivariate logistic regression analysis. RESULTS: A total of 1,179 (60.3%)
      students reported having had their sexual debut. Of these, 231 (37.4%) males and
      209 (49.2%) females reported inconsistent condom use with a new sex partner.
      Students with low condom efficacy had a higher risk of inconsistent condom use
      with a new sex partner, even after adjusting for the potential confounders. A
      synergistic effect was observed between being a female and low condom efficacy
      with inconsistent condom use. CONCLUSION: The association between inconsistent
      condom use and low condom efficacy was found among both males and females, but
      females were found to be at a higher risk of inconsistent condom use compared to
      their male counterparts. Therefore, gender power relations should be addressed in
      policies and interventions aiming at increasing condom use among young people in
      sub-Saharan settings. Programs could be designed with intervention strategies
      that focus on interactive and participatory educational activities and youth
      friendly counseling of young people, which in turn may improve their
      interpersonal communication and condom negotiation skills with their partners.

PMID- 24725364
TI  - Epac1 increases migration of endothelial cells and melanoma cells via FGF2
      mediated paracrine signaling.
AB  - Fibroblast growth factor (FGF2) regulates endothelial and melanoma cell
      migration. The binding of FGF2 to its receptor requires N-sulfated heparan
      sulfate (HS) glycosamine. We have previously reported that Epac1, an exchange
      protein activated by cAMP, increases N-sulfation of HS in melanoma. Therefore, we
      examined whether Epac1 regulates FGF2-mediated cell-cell communication.
      Conditioned medium (CM) of melanoma cells with abundant expression of Epac1
      increased migration of human umbilical endothelial cells (HUVEC) and melanoma
      cells with poor expression of Epac1. CM-induced increase in migration was
      inhibited by antagonizing FGF2, by the removal of HS and by the knockdown of
      Epac1. In addition, knockdown of Epac1 suppressed the binding of FGF2 to FGF
      receptor in HUVEC, and in vivo angiogenesis in melanoma. Furthermore, knockdown
      of Epac1 reduced N-sulfation of HS chains attached to perlecan, a major secreted
      type of HS proteoglycan that mediates the binding of FGF2 to FGF receptor. These
      data suggested that Epac1 in melanoma cells regulates melanoma progression via
      the HS-FGF2-mediated cell-cell communication.

PMID- 24725367
TI  - Development of novel nanocomposite adsorbent based on potassium nickel
      hexacyanoferrate-loaded polypropylene fabric.
AB  - A nanocomposite adsorbent based on potassium nickel hexacyanoferrate-loaded
      polypropylene fabric was synthesized for selective removal of Cs ions from
      contaminated waters by a two-stage synthesis: radiation-induced graft
      polymerization of acrylic acid monomer onto the nonwoven polypropylene fabric
      surface with subsequent in situ formation of potassium nickel hexacyanoferrate
      (KNiHCF) nanoparticles within the grafted chains. Data of scanning electron
      microscopy, X-ray diffraction, and Fourier transform infrared spectroscopy
      confirmed the formation of KNiHCF homogeneous phase on the fabric surface, which
      consisted of crystalline cubic-shaped nanoparticles (70 to 100 nm). The
      efficiency of the synthesized adsorbent for removal of cesium ions was evaluated
      under various experimental conditions. It has demonstrated a rapid adsorption
      process, high adsorption capacity over a wide pH range, and selectivity in Cs ion
      removal from model solutions with high concentration of sodium ions. 

PMID- 24725366
TI  - Muscle histopathology in nebulin-related nemaline myopathy: ultrastrastructural
      findings correlated to disease severity and genotype.
AB  - Nemaline myopathy (NM) is a rare congenital myopathy characterised by hypotonia,
      muscle weakness, and often skeletal muscle deformities with the presence of
      nemaline bodies (rods) in the muscle biopsy. The nebulin (NEB) gene is the most
      commonly mutated and is thought to account for approximately 50% of genetically
      diagnosed cases of NM. We undertook a detailed muscle morphological analysis of
      14 NEB-mutated NM patients with different clinical forms to define muscle
      pathological patterns and correlate them with clinical course and genotype. Three
      groups were identified according to clinical severity. Group 1 (n = 5) comprises
      severe/lethal NM and biopsy in the first days of life. Group 2 (n = 4) includes
      intermediate NM and biopsy in infancy. Group 3 (n = 5) comprises typical/mild NM
      and biopsy in childhood or early adult life. Biopsies underwent
      histoenzymological, immunohistochemical and ultrastructural analysis. Fibre type
      distribution patterns, rod characteristics, distribution and localization were
      investigated. Contractile performance was studied in muscle fibre preparations
      isolated from seven muscle biopsies from each of the three groups. G1 showed
      significant myofibrillar dissociation and smallness with scattered globular rods
      in one third of fibres; there was no type 1 predominance. G2 presented milder
      sarcomeric dissociation, dispersed or clustered nemaline bodies, and type 1
      predominance/uniformity. In contrast, G3 had well-delimited clusters of
      subsarcolemmal elongated rods and type 1 uniformity without sarcomeric
      alterations. In accordance with the clinical and morphological data, functional
      studies revealed markedly low forces in muscle bundles from G1 and a better
      contractile performance in muscle bundles from biopsies of patients from G2, and
      G3.In conclusion NEB-mutated NM patients present a wide spectrum of morphological
      features. It is difficult to establish firm genotype phenotype correlation.
      Interestingly, there was a correlation between clinical severity on the one hand
      and the degree of sarcomeric dissociation and contractility efficiency on the
      other. By contrast the percentage of fibres occupied by rods, as well as the
      quantity and the sub sarcolemmal position of rods, appears to inversely correlate
      with severity. Based on our observations, we propose myofibrillar dissociation
      and changes in contractility as an important cause of muscle weakness in NEB
      mutated NM patients.

PMID- 24725365
TI  - Genome-wide analysis and expression profile of the bZIP transcription factor gene
      family in grapevine (Vitis vinifera).
AB  - BACKGROUND: Basic leucine zipper (bZIP) transcription factor gene family is one
      of the largest and most diverse families in plants. Current studies have shown
      that the bZIP proteins regulate numerous growth and developmental processes and
      biotic and abiotic stress responses. Nonetheless, knowledge concerning the
      specific expression patterns and evolutionary history of plant bZIP family
      members remains very limited. RESULTS: We identified 55 bZIP transcription factor
      encoding genes in the grapevine (Vitis vinifera) genome, and divided them into 10
      groups according to the phylogenetic relationship with those in Arabidopsis. The
      chromosome distribution and the collinearity analyses suggest that expansion of
      the grapevine bZIP (VvbZIP) transcription factor family was greatly contributed
      by the segment/chromosomal duplications, which may be associated with the
      grapevine genome fusion events. Nine intron/exon structural patterns within the
      bZIP domain and the additional conserved motifs were identified among all VvbZIP
      proteins, and showed a high group-specificity. The predicted specificities on DNA
      binding domains indicated that some highly conserved amino acid residues exist
      across each major group in the tree of land plant life. The expression patterns
      of VvbZIP genes across the grapevine gene expression atlas, based on microarray
      technology, suggest that VvbZIP genes are involved in grapevine organ
      development, especially seed development. Expression analysis based on qRT-PCR
      indicated that VvbZIP genes are extensively involved in drought- and heat
      responses, with possibly different mechanisms. CONCLUSIONS: The genome-wide
      identification, chromosome organization, gene structures, evolutionary and
      expression analyses of grapevine bZIP genes provide an overall insight of this
      gene family and their potential involvement in growth, development and stress
      responses. This will facilitate further research on the bZIP gene family
      regarding their evolutionary history and biological functions.

PMID- 24725368
TI  - Prevalence of radiographic findings of femoroacetabular impingement in the
      Japanese population.
AB  - BACKGROUND: Femoroacetabular impingement (FAI) is one factor known to cause pain
      and osteoarthritis (OA) of the hips. Although secondary OA due to hip dysplasia
      is common among Japanese populations, primary OA is seldom observed.
      Concomitantly, FAI is also thought to be uncommon in Japan, but relatively few
      epidemiological studies have addressed this issue. This study aimed to clarify
      the prevalence of radiographic findings of FAI in a Japanese population and to
      evaluate whether FAI is a risk factor for the development of arthritic changes.
      METHODS: We retrospectively examined 87 patients who underwent unilateral hip
      osteotomy with a Charnley category A hip joint on the contralateral side.
      Anteroposterior-view radiographs of the non-operated hip joint were assessed for
      the presence of hip dysplasia, as well as pistol grip deformity and crossover
      sign indicative of cam-type and pincer-type impingement, respectively. The
      presence of arthritic changes in the non-operated hip joint was assessed in
      follow-up radiographs, and factors contributing to the development of arthritis
      were determined by survival analysis. RESULTS: Of the 87 hips examined, dysplasia
      was noted in 38 (43.6%). While no pistol grip deformity was observed, crossover
      sign, which is indicative of pincer-type impingement, was identified in 9 of 38
      dysplastic hips (23.7%) and 15 of 49 non-dysplastic hips (30.6%). Arthritic
      changes were present in 13 of 38 dysplastic hips (34.2%) and 11 of 49 non
      dysplastic hips (22.4%). Survival analysis revealed that the presence of the
      crossover sign in non-dysplastic hips was significantly associated with the
      development of arthritis. CONCLUSIONS: The prevalence of the crossover sign in
      hips in a Japanese population is similar to that reported in Western populations,
      despite the fact that FAI is believed to be less prevalent in the Japanese
      population. Furthermore, the presence of the crossover sign in non-dysplastic hip
      joints is associated with the development of arthritis. Based on our results,
      pincer-type impingement could be commonly associated with the development of
      arthritis in Japanese populations.

PMID- 24725370
TI  - Improving Communication in ADHD Care: Results from In-office Linguistic Research.
AB  - IntroductionAn in-office linguistic study was conducted to help improve
      understanding of how to better evaluate and treat attention-deficit/hyperactivity
      disorder (ADHD). METHODS: Naturally occurring interactions were recorded among 7
      psychiatrists and 23 patients and 8 pediatricians along with 22 patients and
      their parents. Participants were interviewed separately post-visit. Transcripts
      of interactions and interviews were analyzed using sociolinguistic techniques.
      RESULTS: Visits were variable in length and lacked concrete treatment plans. In
      the pediatric setting, children were typically excluded from dialogues,
      accounting for only 8% of words spoken. School was the primary metric used to
      evaluate symptoms. Pediatricians allayed parents' concerns about stimulant
      therapy by promising to prescribe the lowest possible dose, rather than
      discussing titrating to an optimal dose. Adults were evaluated idiosyncratically
      without the use of scales or tools. Stimulants were positioned as short-term
      "trials" without strong physician recommendations.DiscussionConversations about
      stimulant therapy lacked goal- and expectation-setting. Also missing from
      conversations was a definitive treatment plan based on the core symptoms of ADHD.
      Incorporating open-ended questions and tools or rating scales may result in a
      more effective and efficient in-office dialogue. CONCLUSION: Further research is
      warranted to assess the efficacy of communication strategies to enhance in-office
      discussions of ADHD and stimulant therapy.

PMID- 24725369
TI  - Benefits of whole body vibration training in patients hospitalised for COPD
      exacerbations - a randomized clinical trial.
AB  - BACKGROUND: Patients with stable COPD show improvements in exercise capacity and
      muscular function after the application of whole body vibration. We aimed to
      evaluate whether this modality added to conventional physiotherapy in exacerbated
      hospitalised COPD patients would be safe and would improve exercise capacity and
      quality of life. METHODS: 49 hospitalised exacerbated COPD patients were
      randomized (1:1) to undergo physiotherapy alone or physiotherapy with the
      addition of whole body vibration. The primary endpoint was the between-group
      difference of the 6-minute walking test (day of discharge - day of admission).
      Secondary assessments included chair rising test, quality of life, and serum
      marker analysis. RESULTS: Whole body vibration did not cause procedure-related
      adverse events. Compared to physiotherapy alone, it led to significantly stronger
      improvements in 6-minute walking test (95.55 +/- 76.29 m vs. 6.13 +/- 81.65 m; p
      = 0.007) and St. Georges Respiratory Questionnaire (-6.43 +/- 14.25 vs. 5.59 +/-
      19.15, p = 0.049). Whole body vibration increased the expression of the
      transcription factor peroxisome proliferator receptor gamma coactivator-1-alpha
      and serum levels of irisin, while it decreased serum interleukin-8. CONCLUSION:
      Whole body vibration during hospitalised exacerbations did not cause procedure
      related adverse events and induced clinically significant benefits regarding
      exercise capacity and health-related quality of life that were associated with
      increased serum levels of irisin, a marker of muscle activity. TRIAL
      REGISTRATION: German Clinical Trials Register DRKS00005979. Registered 17 March
      2014.

PMID- 24725371
TI  - A Complex Case of Neuro-Behcet's Disease in a Patient Previously Diagnosed with
      multiple Sclerosis: A Case Report.
AB  - Multiple sclerosis (MS) and Neuro-Behcet's disease (NBD) have been associated
      with a range of neuropsychiatric symptoms, including fatigue, cognitive
      impairment, depression, bipolar disorder, anxiety, sexual dysfunction, and other
      behavioral disturbances that are characterized by remissions and exacerbations at
      different points during the course of the disease. We present an interesting case
      of NBD in a 48-year-old female who had previously been diagnosed with MS.
      Exploration of this patient's various neuropsychiatric symptoms, their
      misattribution first to psychopathology and then subsequently to a variety of
      neurological problems exemplifies the potential pitfalls in diagnosis of a
      seemingly rare disorder. The role of psychosocial stress-related inflammatory
      changes in the patient's behavioral and neurological symptoms is explored as well
      as the potential psychological and medical effects of delayed diagnosis and
      treatment. 

PMID- 24725372
TI  - What is not "Effective" in Mild to Moderate Depression: Antidepressants or the
      Hamilton Rating Scale for Depression?

PMID- 24725373
TI  - Comparison of capnovolumetry-derived dead space parameters with pulmonary
      function test in normal adults using histamine provocation.
AB  - OBJECTIVES: This study in healthy adults was conducted to explore the clinical
      application of capnovolumetric indices as compared to lung function parameters
      using histamine provocation. METHODS: Forty healthy subjects received aerosol
      histamine or salbutamol in an automatic stimulation system with escalating doses
      of histamine. Dead space volumes of capnovolumetry and lung function parameters
      were examined with increased concentrations of histamine at a fixed time
      interval. The doses of histamine were selected from 0.0562 mg-2.2 mg and 0.1 mg
      salbutamol was inhaled when a maximal dose of histamine was reached. Baseline
      values in each group were calculated prior to histamine inhalation. RESULTS:
      Fowler dead space (VDF), Wolff dead space (VDW), threshold dead space (VDT), Bohr
      dead space (VDB), forced expiratory volume in 1 s (FEV1 ) and peak expiratory
      flow (PEF) showed a dose-dependent reduction following histamine provocation, but
      there were no statistical differences in the measurements at baseline and post S6
      provocation. The value of dC3/DV at the maximal dose was significantly increased
      over its baseline value (P < 0.05). VDF, VDT and VDW were significantly increased
      after bronchodilator use (P < 0.05 or <0.01). The changes in capnovolumetry did
      not correspond with the results of lung function test. CONCLUSIONS: The dC3/DV
      and airway dead spaces of capnovolumetry in healthy adults are significantly
      increased compared to lung function parameters before or after bronchodilator
      use, suggesting that capnovolumetry is feasible in diagnostic evaluation of
      airway reactivity, especially for persons who are unable to undertake lung
      function test.

PMID- 24725375
TI  - DNA barcoding of five common stored-product pest species of genus Cryptolestes
      (Coleoptera: Laemophloeidae).
AB  - Several species of the genus Cryptolestes Ganglbauer, 1899 (Coleoptera:
      Laemophloeidae) are commonly found in stored products. In this study, five
      species of Cryptolestes, with almost worldwide distribution, were obtained from
      laboratories in China, Czech Republic and the USA: Cryptolestes ferrugineus
      (Stephens, 1831), Cryptolestes pusillus (Schonherr, 1817), Cryptolestes turcicus
      (Grouvelle, 1876), Cryptolestes pusilloides (Steel & Howe, 1952) and Cryptolestes
      capensis (Waltl, 1834). Molecular identification based on a 658 bp fragment from
      the mitochondrial DNA cytochrome c oxidase subunit I (COI) was adopted to
      overcome some problems of morphological identification of Cryptolestes species.
      The utility of COI sequences as DNA barcodes in discriminating the five
      Cryptolestes species was evaluated on adults and larvae by analysing Kimura 2
      parameter distances, phylogenetic tree and haplotype networks. The results showed
      that molecular approaches based on DNA barcodes were able to accurately identify
      these species. This is the first study using DNA barcoding to identify
      Cryptolestes species and the gathered DNA sequences will complement the
      biological barcode database.

PMID- 24725376
TI  - Characterization of the interaction between a SirR family transcriptional factor
      of Mycobacterium tuberculosis, encoded by Rv2788, and a pair of toxin-antitoxin
      proteins RelJ/K, encoded by Rv3357 and Rv3358.
AB  - Toxin-antitoxin (TA) systems play significant roles in the regulation of
      bacterial growth and persistence, and their functions usually depend on protein
      protein interaction between their constituent TA proteins. However, the
      regulatory mechanisms of these systems, particularly their interaction with other
      cellular components, are still poorly understood. This study investigated cross
      talk between the TA module RelJ/K (Rv3357/Rv3358) and the transcriptional
      regulator staphylococcal iron regulator repressor (SirR, Rv2788) from
      Mycobacterium tuberculosis. We characterized the physical interaction of SirR
      with both RelJ and RelK using bacterial two-hybrid, pull-down and co
      immunoprecipitation assays. Similarly to RelK, SirR regulates the DNA-binding
      activity of RelJ and alleviates its inhibitory effect on the activity of the
      Rv3357p promoter. Furthermore, SirR may replace RelJ to alleviate the inhibitory
      effect of the toxin RelK on bacterial growth. Conversely, both RelJ and RelK
      competitively inhibit the interaction between SirR and their respective
      promoters. Thus, our results show that SirR interacts with a pair of toxin and
      antitoxin proteins, and exhibits antitoxin-like function to neutralize the toxin.
      These findings demonstrate a novel function of the SirR regulator of M.
      tuberculosis as well as a novel mechanism of regulation of TA systems.

PMID- 24725374
TI  - Housing First: exploring participants' early support needs.
AB  - BACKGROUND: Housing First has become a popular treatment model for homeless
      adults with mental illness, yet little is known about program participants' early
      experiences or trajectories. This study used a mixed methods design to examine
      participant changes in selected domains 6 months after enrollment in a Canadian
      field trial of Housing First. METHODS: The study sample included 301 participants
      receiving the Housing First intervention at the Toronto site of the At Home/Chez
      Soi project. This study used a pre-post design to compare quantitative 6-month
      outcome data to baseline values in key domains and multivariate regression to
      identify baseline demographic, clinical or service use variables associated with
      observed changes in these domains. In addition, qualitative data exploring
      participant and service provider perspectives and experiences was collected via
      stakeholder interviews and focus groups, and analyzed using thematic analysis.
      RESULTS: The majority (60 to 72%) of participants followed the expected
      trajectory of improvement, with the remaining experiencing difficulties in
      community integration, mental health symptom severity, substance use, community
      functioning and quality of life 6 months after program enrollment. Diagnosis of
      psychotic disorder was associated with a reduction in quality of life from
      baseline to 6-months, while substance use disorders were associated with reduced
      mental illness symptoms and substance use related problems and an improvement in
      quality of life. Participants housed in independent housing at 6-months had
      greater improvements in community integration and quality of life, and greater
      reduction in mental illness symptoms, compared to those not independently housed.
      The quality of the working alliance was positively associated with improvements
      in physical and psychological community integration and quality of life.
      Qualitative data provided a unique window into the loneliness and isolation
      experienced by Housing First participants, as well as problems related to
      substance use and a need for life skills training and support. CONCLUSIONS:
      Additional strategies can help support Housing First participants in the early
      stages of program participation and address potential causes of early
      difficulties, including lack of life skills and social isolation. This study
      highlights the importance of early and ongoing evaluation, monitoring and program
      adaptations to address consumer support needs. TRIAL REGISTRATION: Current
      Controlled Trials ISRCTN42520374.

PMID- 24725377
TI  - Bile cast nephropathy: an often forgotten diagnosis.
AB  - High bilirubin levels are nephrotoxic. Bilirubin can cause a functional proximal
      tubulopathy or may precipitate into casts associated with acute tubular injury.
      This condition is known as bile cast nephropathy. The kidney injury is generally
      reversible if bilirubin levels are decreased early. We present a case wherein an
      alcoholic patient presented with high bilirubin levels and anuric acute kidney
      injury. The initial urine analysis suggested intrinsic renal disease. A kidney
      biopsy, performed a few days after the initiation of dialysis, demonstrated the
      presence of bile casts along with acute tubular injury. The patient however
      continued to be dialysis dependent inspite of initiating prednisolone to treat
      acute alcoholic hepatitis. 

PMID- 24725378
TI  - A simple ex vivo model for teaching Descemet membrane endothelial keratoplasty.
AB  - PURPOSE: To describe a simple ex vivo porcine model for teaching Descemet
      Membrane Endothelial Keratoplasty (DMEK). METHODS: Twenty freshly enucleated
      porcine eyes were used to create a pseudo-graft from the porcine lens capsule and
      implant it into an intact porcine globe using the standardized 'no-touch'
      technique of the Netherlands Institute for Innovative Ocular Surgery (NIIOS).
      RESULTS: The DMEK pseudo-graft could be inserted, centred, unfolded and
      appositioned in all cases. CONCLUSIONS: Practicing DMEK surgery under wetlab
      conditions was feasible by the described simple and low-cost model. This new tool
      may facilitate the adaptation of DMEK by cornea surgeons.

PMID- 24725379
TI  - Rethinking dry eye disease: a perspective on clinical implications.
AB  - Publication of the DEWS report in 2007 established the state of the science of
      dry eye disease (DED). Since that time, new evidence suggests that a rethinking
      of traditional concepts of dry eye disease is in order. Specifically, new
      evidence on the epidemiology of the disease, as well as strategies for diagnosis,
      have changed the understanding of DED, which is a heterogeneous disease
      associated with considerable variability in presentation. These advances, along
      with implications for clinical care, are summarized herein. The most widely used
      signs of DED are poorly correlated with each other and with symptoms. While
      symptoms are thought to be characteristic of DED, recent studies have shown that
      less than 60% of subjects with other objective evidence of DED are symptomatic.
      Thus the use of symptoms alone in diagnosis will likely result in missing a
      significant percentage of DED patients, particularly with early/mild disease.
      This could have considerable impact in patients undergoing cataract or refractive
      surgery as patients with DED have less than optimal visual results. The most
      widely used objective signs for diagnosing DED all show greater variability
      between eyes and in the same eye over time compared with normal subjects. This
      variability is thought to be a manifestation of tear film instability which
      results in rapid breakup of the tearfilm between blinks and is an identifier of
      patients with DED. This feature emphasizes the bilateral nature of the disease in
      most subjects not suffering from unilateral lid or other unilateral destabilizing
      surface disorders. Instability of the composition of the tears also occurs in dry
      eye disease and shows the same variance between eyes. Finally, elevated tear
      osmolarity has been reported to be a global marker (present in both subtypes of
      the disease- aqueous-deficient dry eye and evaporative dry eye). Clinically,
      osmolarity has been shown to be the best single metric for diagnosis of DED and
      is directly related to increasing severity of disease. Clinical examination and
      other assessments differentiate which subtype of disease is present. With
      effective treatment, the tear osmolarity returns to normal, and its variability
      between eyes and with time disappears. Other promising markers include objective
      measures of visual deficits, proinflammatory molecular markers and other
      molecular markers, specific to each disease subtype, and panels of tear proteins.
      As yet, however, no single protein or panel of markers has been shown to
      discriminate between the major forms of DED. With the advent of new tests and
      technology, improved endpoints for clinical trials may be established, which in
      turn may allow new therapeutic agents to emerge in the foreseeable future.
      Accurate recognition of disease is now possible and successful management of DED
      appears to be within our grasp, for a majority of our patients. 

PMID- 24725380
TI  - Treatment of acute kidney injury with cast nephropathy.
AB  - Nearly 50% of patients with multiple myeloma develop renal disease; acute kidney
      injury (AKI) from cast nephropathy, or "myeloma kidney" is the most common type.
      Development of AKI is associated with worse 1-year survival and reduces the
      therapeutic options available to patients. Therefore, there is a great need to
      develop more effective therapies. Cast nephropathy is due to the interaction and
      aggregation of filtered free light chains (FLCs) and Tamm- Horsfall protein (THP)
      causing intratubular obstruction and damage. The key to treating cast nephropathy
      is rapid lowering of FLCs as this correlates with renal recovery. Newer
      chemotherapy agents lower FLCs and have been referred to as "renoprotective".
      However there remains great interest in using various extracorporeal therapies to
      remove serum FLCs. Initially, therapeutic plasma exchange (TPE) was thought to
      improve renal outcomes in cast nephropathy based on small trials. The largest
      randomized trial of TPE, however, failed to show any benefit. A newer technique
      is extended high cut-off hemodialysis (HCO-HD). This modality uses a high
      molecular weight cut-off filter to remove FLCs. To date, trials with HCO-HD in
      patients with cast nephropathy have been encouraging. However, there are no
      randomized trials demonstrating the benefit of HCOHD when used in addition to
      newer chemotherapeutic regimens. Until these studies are available, HCO-HD cannot
      be recommended as standard of care. 

PMID- 24725381
TI  - Trends in oral cavity, pharyngeal, oesophageal and gastric cancer mortality rates
      in Spain, 1952-2006: an age-period-cohort analysis.
AB  - BACKGROUND: Although oral cavity, pharyngeal, oesophageal and gastric cancers
      share some risk factors, no comparative analysis of mortality rate trends in
      these illnesses has been undertaken in Spain. This study aimed to evaluate the
      independent effects of age, death period and birth cohort on the mortality rates
      of these tumours. METHODS: Specific and age-adjusted mortality rates by tumour
      and sex were analysed. Age-period-cohort log-linear models were fitted separately
      for each tumour and sex, and segmented regression models were used to detect
      changes in period- and cohort-effect curvatures. RESULTS: Among men, the period
      effect curvatures for oral cavity/pharyngeal and oesophageal cancers displayed a
      mortality trend that rose until 1995 and then declined. Among women, oral
      cavity/pharyngeal cancer mortality increased throughout the study period whereas
      oesophageal cancer mortality decreased after 1970. Stomach cancer mortality
      decreased in both sexes from 1965 onwards. Lastly, the cohort-effect curvature
      showed a certain degree of similarity for all three tumours in both sexes, which
      was greater among oral cavity, pharyngeal and oesophageal cancers, with a change
      point in evidence, after which risk of death increased in cohorts born from the
      1910-1920s onwards and decreased among the 1950-1960 cohorts and successive
      generations. This latter feature was likewise observed for stomach cancer.
      CONCLUSIONS: While the similarities of the cohort effects in oral
      cavity/pharyngeal, oesophageal and gastric tumours support the implication of
      shared risk factors, the more marked changes in cohort-effect curvature for oral
      cavity/pharyngeal and oesophageal cancer could be due to the greater influence of
      some risk factors in their aetiology, such as smoking and alcohol consumption.
      The increase in oral cavity/pharyngeal cancer mortality in women deserves further
      study.

PMID- 24725382
TI  - Trehalose synthesis in Aspergillus niger: characterization of six homologous
      genes, all with conserved orthologs in related species.
AB  - BACKGROUND: The disaccharide trehalose is a major component of fungal spores and
      is released upon germination. Moreover, the sugar is well known for is protective
      functions, e.g. against thermal stress and dehydration. The properties and
      synthesis of trehalose have been well investigated in the bakers' yeast
      Saccharomyces cerevisiae. In filamentous fungi, such knowledge is limited,
      although several gene products have been identified. RESULTS: Using Aspergillus
      niger as a model fungus, the aim of this study was to provide an overview of all
      genes involved in trehalose synthesis. This fungus has three potential trehalose
      6-phosphate synthase encoding genes, tpsA-C, and three putative trehalose
      phosphate phosphatase encoding genes, tppA-C, of which two have not previously
      been identified. Expression of all six genes was confirmed using real-time PCR,
      and conserved orthologs could be identified in related Aspergilli. Using a two
      hybrid approach, there is a strong indication that four of the proteins
      physically interact, as has previously been shown in S. cerevisiae. When creating
      null mutants of all the six genes, three of them, DeltatpsA, DeltatppA and
      DeltatppB, had lower internal trehalose contents. The only mutant with a
      pronounced morphological difference was DeltatppA, in which sporulation was
      severely reduced with abnormal conidiophores. This was also the only mutant with
      accumulated levels of trehalose-6-phosphate, indicating that the encoded protein
      is the main phosphatase under normal conditions. Besides DeltatppA, the most
      studied deletion mutant in this work was DeltatppB. This gene encodes a protein
      conserved in filamentous Ascomycota. The DeltatppB mutant displayed a low, but
      not depleted, internal trehalose content, and conidia were more susceptible to
      thermal stress. CONCLUSION: A. niger contains at least 6 genes putatively
      involved in trehalose synthesis. Gene expressions related to germination have
      been quantified and deletion mutants characterized: Mutants lacking tpsA, tppA or
      tppB have reduced internal trehalose contents. Furthermore, tppA, under normal
      conditions, encodes the functional trehalose-6-phosphate-phosphatase.

PMID- 24725384
TI  - Aerobic dynamic feeding as a strategy for in situ accumulation of
      polyhydroxyalkanoate in aerobic granules.
AB  - Aerobic dynamic feeding (ADF) strategy was applied in sequencing batch reactor
      (SBR) to accumulate polyhydroxyalkanoate (PHA) in aerobic granules. The aerobic
      granules were able to remove 90% of the COD from palm oil mill effluent (POME).
      The volatile fatty acids (VFAs) in the POME are the sole source of the PHA
      accumulation. In this work, 100% removal of propionic and butyric acids in the
      POME were observed. The highest amount of PHA produced in aerobic granules was
      0.6833mgPHA/mgbiomass. The PHA formed was identified as a P (hydroxybutyrate-co
      hydroxyvalerate) P (HB-co-HV). 

PMID- 24725383
TI  - Non-terminal respiratory unit type lung adenocarcinoma has three distinct
      subtypes and is associated with poor prognosis.
AB  - OBJECTIVES: The characteristics of non-terminal respiratory unit (TRU) type lung
      adenocarcinoma are still unclear. The aim of the present study was to
      characterize non-TRU type lung adenocarcinoma. MATERIALS AND METHODS: We analyzed
      the expression of mucins MUC5B and MUC5AC, as well as thyroid transcription
      factor-1 (TTF-1), using a tissue microarray comprising lung adenocarcinoma
      specimens from 244 consecutive patients. The presence of mutations in EGFR and
      KRAS were also determined. RESULTS: TTF-1, MUC5B, and MUC5AC were detected in 219
      (89.8%), 75 (30.7%), and 33 cases (13.5%), respectively. Cluster analysis of
      protein expression profiles and EGFR and KRAS mutations yielded five groups of
      tumors as follows: TRU1-type [TTF-1(+), MUC5B(-), MUC5AC(-), EGFR mutations(-)];
      TRU2-type [TTF-1(+), MUC5B(-), MUC5AC(-), EGFR mutations(+)]; Combined-type [TTF
      1(+), MUC5B(+), and/or MUC5AC(+)]; Bronchiolar-type [TTF-1(-), MUC5B(+) and/or
      MUC5AC(+)]; and Null-type [TTF-1(-), MUC5B(-), MUC5AC(-), EGFR mutations(-), KRAS
      mutations(-)]. TRU-type tumors, which include TRU1- and TRU2-type tumors, were
      significantly associated with TRU morphology, whereas Bronchiolar-type tumors
      were associated with non-TRU morphology. Combined-type cases exhibited
      intermediate morphologies between TRU-type and Bronchiolar-type cases. TRU-type
      was associated with significantly better prognosis, followed by Combined-type,
      Bronchiolar-type, and Null-type (disease-free survival [DFS] P = 0.017; overall
      survival [OS], P = 0.002). Multivariate analyses indicated that non-TRU type
      tumors, which include Bronchiolar-, Combined-, Null-type tumors, were
      significantly correlated with poorer prognoses for DFS (hazard ratio = 1.785; 95%
      CI, 1.041-3.063; P = 0.035) and OS (hazard ratio = 1.928; 95% CI, 1.084-3.421; P
      = 0.025). CONCLUSION: This study revealed three distinct subtypes of non-TRU type
      adenocarcinomas. Additionally, non-TRU type tumors were associated with worse
      prognoses than TRU type tumors. The results presented here may be useful for
      select patients should appropriate therapies become available.

PMID- 24725385
TI  - Novel thermostable endo-xylanase cloned and expressed from bacterium Geobacillus
      sp. WSUCF1.
AB  - A gene encoding a GH10 endo-xylanase from Geobacillus sp. WSUCF1 was cloned and
      expressed in Escherichia coli. Recombinant endo-xylanase (37kDa) exhibited high
      specific activity of 461.0U/mg of protein. Endo-xylanase was optimally active on
      birchwood xylan at 70 degrees C and pH 6.5. The endo-xylanase was found to be
      highly thermostable at 50 and 60 degrees C, retaining 82% and 50% of its original
      activity, respectively, after 60h. High xylan conversions (92%) were obtained
      with oat-spelt xylan hydrolysis. Higher glucan and xylan conversions were
      obtained on AFEX-treated corn stover with an enzyme cocktail containing WSUCF1
      endo-xylanase (71% and 47%) as compared to enzyme cocktail containing commercial
      fungal endo-xylanase (64% and 41%). High specific activity, active at high pH's,
      wide substrate specificity, and higher hydrolytic activity on recalcitrant
      lignocellulose, make this endo-xylanase a suitable candidate for biofuel and
      bioprocess industries. 

PMID- 24725386
TI  - White Matter Changes in OCD Revealed by Diffusion Tensor Imaging.
AB  - IntroductionThe aim of this study was to investigate white matter (WM)
      abnormalities in obsessive-compulsive disorder (OCD) and its relationship to
      severity of obsessive-compulsive symptoms. METHODS: Conventional and diffusion
      tensor imaging were acquired in nine patients with OCD and nine gender- and age
      matched healthy volunteers. Changes in fractional anisotropy (FA) and mean
      diffusivity (MD) were investigated using selected regions of interest (ROIs)
      analyses and whole brain tract-based spatial statistic analyses. A priori ROIs
      were placed bilaterally in internal capsule (IC), superior longitudinal fascicule
      (SLF), cingulate bundle (CB), and corpus calosum (CC). RESULTS: ROIs analyses
      showed that, as compared to healthy volunteers, patients with OCD exhibited
      reduced FA values bilaterally in regions of the posterior limb of the IC and in
      the SLF and increased MD values bilaterally in the posterior limb of the IC, in
      the left CB, and in the splenium of CC. Voxelwise analysis showed that, as
      compared to controls, patients with OCD exhibited reduced FA and increased MD in
      regions of the cortical spinal tract (genu and posterior limb of internal capsule
      and corona radiata) and the SLF. Severity of OCD correlated with WM alterations
      in different brain regions, ie, the left (rho=0.70 [MD]) and right (rho=0.70
      [MD]) anterior limb of the IC, the left (rho=0.97 [MD]) and right SLF (rho=0.81
      [MD]), and the genu of CC (rho=0.66 [MD]; rho=-0.69 [FA]). CONCLUSION: Our
      findings support the involvement of different WM tracts in OCD and suggest that
      greater impairment in WM integrity is associated with increased severity of OCD
      symptoms.

PMID- 24725387
TI  - Quantitative EEG Spectrum-weighted Frequency (Brain Rate) Distribution in Adults
      with ADHD.
AB  - OBJECTIVE: The aim of this study is to explore the applicability of brain rate
      (fb) for the diagnosis of attention-deficit/hyperactivity disorder (ADHD),
      analyzing the spatial distribution of fb through analysis of its values in
      sagittal and lateral electrodes' positions, recorded in four conditions (eyes
      closed, eyes opened, visual continuous performance task and emotional continuous
      performance task). METHODS: Sixty-seven adults diagnosed with ADHD according to
      Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria
      and 50 age-matched control subjects participated in the study. The brain activity
      of the subjects was recorded by 19 channel quantitative electroencephalography
      (QEEG) system and fb was calculated with the fb software. RESULTS: Maximum values
      of fb for sagittal topography are obtained in central region and the minimum in
      frontal region, while lateral topography maximum values are found in the left and
      right sides and the minimum in midline region. A positive correlation between the
      fb values and the QEEG spectra subtypes was obtained, with lower values for
      normals, first and second subtype, and higher values for the third and fourth
      subtype. On the other hand, there was no correlation between behavioral symptoms
      and fb values. CONCLUSION: The applicability of an fb indicator in the diagnosis
      of ADHD is especially pronounced for the higher subtypes (ADHD III and IV),
      corresponding to heterogeneous and multifactorial character of this disorder.

PMID- 24725388
TI  - Subarachnoid hemorrhage in wegener granulomatosis: a case report and review of
      the literature.
AB  - Wegener granulomatosis (WG) is an uncommon, idiopathic disorder that is
      characterized by granulomatous inflammation of the upper and lower respiratory
      tract, disseminated vasculitis involving small and medium-sized vessels, and
      focal segmental glomerulonephritis. Approximately 25% to 50% of patients have
      nervous system involvement. The brain is less frequently involved. We report a
      case of a 74 year-old previously well woman who presented with rapidly
      progressing WG that culminated in subarachnoid hemorrhage. Only six cases of
      subarachnoid hemorrhage in the setting of WG have previously been reported. We
      review the common presenting signs and symptoms, diagnosis, treatment, and
      complications of WG. 

PMID- 24725390
TI  - Bimetallic non-alloyed NPs for improving the broadband optical absorption of thin
      amorphous silicon substrates.
AB  - We propose the use of bimetallic non-alloyed nanoparticles (BNNPs) to improve the
      broadband optical absorption of thin amorphous silicon substrates. Isolated
      bimetallic NPs with uniform size distribution on glass and silicon are obtained
      by depositing a 10-nm Au film and annealing it at 600 degrees C; this is followed
      by an 8-nm Ag film annealed at 400 degrees C. We experimentally demonstrate that
      the deposition of gold (Au)-silver (Ag) bimetallic non-alloyed NPs (BNNPs) on a
      thin amorphous silicon (a-Si) film increases the film's average absorption and
      forward scattering over a broad spectrum, thus significantly reducing its total
      reflection performance. Experimental results show that Au-Ag BNNPs fabricated on
      a glass substrate exhibit resonant peaks at 437 and 540 nm and a 14-fold increase
      in average forward scattering over the wavelength range of 300 to 1,100 nm in
      comparison with bare glass. When deposited on a 100-nm-thin a-Si film, Au-Ag
      BNNPs increase the average absorption and forward scattering by 19.6% and 95.9%
      compared to those values for Au NPs on thin a-Si and plain a-Si without MNPs,
      respectively, over the 300- to 1,100-nm range. 

PMID- 24725391
TI  - HPV vaccine uptake among Asian American girls aged 9-17 years during 2008-2010.

PMID- 24725389
TI  - Stress responses go three dimensional - the spatial order of physiological
      differentiation in bacterial macrocolony biofilms.
AB  - In natural habitats, bacteria often occur in multicellular communities
      characterized by a robust extracellular matrix of proteins, amyloid fibres,
      exopolysaccharides and extracellular DNA. These biofilms show pronounced stress
      resistance including a resilience against antibiotics that causes serious medical
      and technical problems. This review summarizes recent studies that have revealed
      clear spatial physiological differentiation, complex supracellular architecture
      and striking morphology in macrocolony biofilms. By responding to gradients of
      nutrients, oxygen, waste products and signalling compounds that build up in
      growing biofilms, various stress responses determine whether bacteria grow and
      proliferate or whether they enter into stationary phase and use their remaining
      resources for maintenance and survival. As a consequence, biofilms differentiate
      into at least two distinct layers of vegetatively growing and stationary phase
      cells that exhibit very different cellular physiology. This includes a
      stratification of matrix production with a major impact on microscopic
      architecture, biophysical properties and directly visible morphology of
      macrocolony biofilms. Using Escherichia coli as a model system, this review also
      describes our detailed current knowledge about the underlying molecular control
      networks - prominently featuring sigma factors, transcriptional cascades and
      second messengers - that drive this spatial differentiation and points out
      directions for future research. 

PMID- 24725392
TI  - Cotyledonoid dissecting leiomyoma.

PMID- 24725393
TI  - Consensus statement on the management of methicillin-resistant Staphylococcus
      aureus nosocomial pneumonia in Asia.
AB  - Nosocomial pneumonia (NP; encompassing hospital-acquired, health care-associated
      and ventilator-associated pneumonia) is one of the most common nosocomial
      infections and is associated with a mortality rate of 18.7%-40.8% in Asian
      countries. The burden of methicillin-resistant Staphylococcus aureus (MRSA)
      infections in Asia is high, and approximately 13% of NP cases in Asia are caused
      by this pathogen. Evidence regarding optimal management of MRSA NP continues to
      evolve and is complicated by the fact that a significant proportion of cases are
      likely to be caused by isolates with reduced susceptibility to the main
      therapeutic agent, vancomycin. The Asian Consensus Taskforce on MRSA Nosocomial
      Pneumonia has developed this statement to provide consensus points on diagnosis,
      antimicrobial treatment and prevention strategies for MRSA NP in the Asian
      context, based on our review of Asian data, previous international guidelines and
      recent scientific evidence. 

PMID- 24725394
TI  - Morphometric evaluation of subaxial cervical spine using multi-detector
      computerized tomography (MD-CT) scan: the consideration for cervical pedicle
      screws fixation.
AB  - BACKGROUND: Cervical pedicle screw (CPS) insertion is a technically demanding
      procedure. The quantitative understanding of cervical pedicle morphology,
      especially the narrowest part of cervical pedicle or isthmus, would minimize the
      risk of catastrophic damage to surrounding neurovascular structures and improve
      surgical outcome. The aim of this study was to investigate morphology and
      quantify cortical thickness of the cervical isthmus by using Multi-detector
      Computerized Tomography (MD-CT) scan. METHODS: The cervical CT scans were
      performed in 74 patients (37 males and 37 females) with 1-mm slice thickness and
      then retro-reconstructed into sagittal and coronal planes to measure various
      cervical parameters as follows: outer pedicle width (OPW), inner pedicle width
      (IPW), outer pedicle height (OPH), inner pedicle height (IPH), pedicle cortical
      thickness, pedicle sagittal angle (PSA), and pedicle transverse angle (PTA).
      RESULTS: Total numbers of 740 pedicles were measured in this present study. The
      mean OPW and IPW significantly increased from C3 to C7 while the mean OPH and IPH
      of those showed non-significant difference between any measured levels. The
      medial-lateral cortical thickness was significantly smaller than the superior
      inferior one. PTA in the upper cervical spine was significantly wider than the
      lower ones. The PSA changed from upward inclination at upper cervical spine to
      the downward inclination at lower cervical spine. CONCLUSIONS: This study has
      demonstrated that cervical vertebra has relatively small and narrow inner pedicle
      canal with thick outer pedicle cortex and also shows a variable in pedicle width
      and inconsistent transverse angle. To enhance the safety of CPS insertion, the
      entry point and trajectories should be determined individually by using
      preoperative MD-CT scan and the inner pedicle width should be a key parameter to
      determine the screw dimensions.

PMID- 24725395
TI  - Single low-dose rHuIL-12 safely triggers multilineage hematopoietic and immune
      mediated effects.
AB  - BACKGROUND: Recombinant human interleukin 12 (rHuIL-12) regulates hematopoiesis
      and cell-mediated immunity. Based on these hematopoietic and immunomodulatory
      activities, a recombinant human IL-12 (rHuIL-12) is now under development to
      address the unmet need for a medical countermeasure against the hematopoietic
      syndrome of the acute radiation syndrome (HSARS) that occurs in individuals
      exposed to lethal radiation, and also to serve as adjuvant therapy that could
      provide dual hematopoietic and immunotherapeutic benefits in patients with cancer
      receiving chemotherapy. We sought to demonstrate in healthy subjects the safety
      of rHuIL-12 at single, low doses that are appropriate for use as a medical
      countermeasure for humans exposed to lethal radiation and as an immunomodulatory
      anti-cancer agent. METHODS: Two placebo-controlled, double-blinded studies
      assessed the safety, tolerability, pharmacokinetics and pharmacodynamics of rHuIL
      12. The first-in-human (FIH) dose-escalation study randomized subjects to single
      subcutaneous injections of placebo or rHuIL-12 at 2, 5, 10, and 20 MUg doses. Due
      to toxicity, dose was reduced to 15 MUg and then to 12 MUg. The phase 1b
      expansion study randomized subjects to the highest safe and well tolerated dose
      of 12 MUg. RESULTS: Thirty-two subjects were enrolled in the FIH study: 4 active
      and 2 placebo at rHuIL-12 doses of 2, 5, 10, 12, and 15 MUg; 1 active and 1
      placebo at 20 MUg. Sixty subjects were enrolled in the expansion study: 48 active
      and 12 placebo at 12 MUg dose of rHuIL-12. In both studies, the most common
      adverse events (AEs) related to rHuIL-12 were headache, dizziness, and chills. No
      immunogenicity was observed. Elimination of rHuIL-12 was biphasic, suggesting
      significant distribution into extravascular spaces. rHuIL-12 triggered transient
      changes in neutrophils, platelets, reticulocytes, lymphocytes, natural killer
      cells, and CD34+ hematopoietic progenitor cells, and induced increases in
      interferon-gamma and C-X-C motif chemokine 10. CONCLUSION: A single low dose of
      rHuIl-12 administered subcutaneously can elicit hematological and immune-mediated
      effects without undue toxicity. The safety and the potent multilineage
      hematopoietic/immunologic effects triggered by low-dose rHuIL-12 support the
      development of rHuIL-12 both as a radiation medical countermeasure and as
      adjuvant immunotherapy for cancer. TRIAL REGISTRATION: ClinicalTrials.gov:
      NCT01742221.

PMID- 24725396
TI  - Shifting ground for big data researchers.
AB  - To harness the strength of data sets growing by leaps and bounds every day,
      cultural norms in biomedical research are under pressure to change with the
      times. 

PMID- 24725397
TI  - Molecular chaperones in cellular protein folding: the birth of a field.
AB  - The early decades of Cell witnessed key discoveries that coalesced into the field
      of chaperones, protein folding, and protein quality control. 

PMID- 24725398
TI  - Driving glioblastoma to drink.
AB  - Attempts to treat cancer with drugs that target mutated proteins have met with
      mixed success. By screening for compounds that alter the phenotype of
      glioblastoma cells-an aggressive brain tumor-Kitambi et al. identify a potential
      new treatment of the disease and shed light on an unusual cell death mechanism.

PMID- 24725399
TI  - Multiplying messages LRRK beneath Parkinson disease.
AB  - Parkinson Disease (PD) is a progressive neurodegenerative disorder with limited
      therapeutic options. In this issue of Cell, Martin et al. link PD protein leucine
      rich repeat kinase 2 (LRRK2) to abnormalities of translational control, a
      pathogenic mechanism implicated in an increasing number of CNS neurodegenerative
      diseases, as well as in normal aging. 

PMID- 24725400
TI  - Peering into the crystal ball: influenza pandemics and vaccine efficacy.
AB  - The looming threat of a new influenza virus pandemic has fueled ambitious efforts
      to devise more predictive parameters for assessing the risks associated with
      emergent virus strains. At the same time, a comprehensive understanding of
      critical factors that can accurately predict the outcome of vaccination is sorely
      needed in order to improve the effectiveness of influenza virus vaccines. Will
      new studies aimed at identifying adaptations required for virus transmissibility
      and systems-level analyses of influenza virus vaccine responses provide an
      improved framework for predictive models of viral adaptation and vaccine
      efficacy? 

PMID- 24725401
TI  - Atomistic autophagy: the structures of cellular self-digestion.
AB  - Autophagy is directed by numerous distinct autophagy-related (Atg) proteins.
      These transmit starvation-induced signals to lipids and regulatory proteins and
      assemble a double-membrane autophagosome sequestering bulk cytoplasm and/or
      selected cargos destined for degradation upon autophagosome fusion with a vacuole
      or lysosome. This Review discusses the structural mechanisms by which Atg
      proteins sense membrane curvature, mediate a PI(3)P-signaling cascade, and
      utilize autophagy-specific ubiquitin-like protein cascades to tether proteins to
      autophagosomal membranes. Recent elucidation of molecular interactions enabling
      vesicle nucleation, elongation, and cargo recruitment provides insights into how
      dynamic protein-protein and protein-membrane interactions may dictate size,
      shape, and contents of autophagosomes. 

PMID- 24725402
TI  - Identification, characterization, and natural selection of mutations driving
      airborne transmission of A/H5N1 virus.
AB  - Recently, A/H5N1 influenza viruses were shown to acquire airborne
      transmissibility between ferrets upon targeted mutagenesis and virus passage. The
      critical genetic changes in airborne A/Indonesia/5/05 were not yet identified.
      Here, five substitutions proved to be sufficient to determine this airborne
      transmission phenotype. Substitutions in PB1 and PB2 collectively caused enhanced
      transcription and virus replication. One substitution increased HA
      thermostability and lowered the pH of membrane fusion. Two substitutions
      independently changed HA binding preference from alpha2,3-linked to alpha2,6
      linked sialic acid receptors. The loss of a glycosylation site in HA enhanced
      overall binding to receptors. The acquired substitutions emerged early during
      ferret passage as minor variants and became dominant rapidly. Identification of
      substitutions that are essential for airborne transmission of avian influenza
      viruses between ferrets and their associated phenotypes advances our fundamental
      understanding of virus transmission and will increase the value of future
      surveillance programs and public health risk assessments. 

PMID- 24725403
TI  - Differentiation of type 1 ILCs from a common progenitor to all helper-like innate
      lymphoid cell lineages.
AB  - Innate lymphoid cells (ILCs) are a recently recognized group of lymphocytes that
      have important functions in protecting epithelial barriers against infections and
      in maintaining organ homeostasis. ILCs have been categorized into three distinct
      groups, transcriptional circuitry and effector functions of which strikingly
      resemble the various T helper cell subsets. Here, we identify a common, Id2
      expressing progenitor to all interleukin 7 receptor-expressing, "helper-like" ILC
      lineages, the CHILP. Interestingly, the CHILP differentiated into ILC2 and ILC3
      lineages, but not into conventional natural killer (cNK) cells that have been
      considered an ILC1 subset. Instead, the CHILP gave rise to a peculiar NKp46(+) IL
      7Ralpha(+) ILC lineage that required T-bet for specification and was distinct of
      cNK cells or other ILC lineages. Such ILC1s coproduced high levels of IFN-gamma
      and TNF and protected against infections with the intracellular parasite
      Toxoplasma gondii. Our data significantly advance our understanding of ILC
      differentiation and presents evidence for a new ILC lineage that protects barrier
      surfaces against intracellular infections.

PMID- 24725404
TI  - Accumulation of dynamic catch bonds between TCR and agonist peptide-MHC triggers
      T cell signaling.
AB  - TCR-pMHC interactions initiate adaptive immune responses, but the mechanism of
      how such interactions under force induce T cell signaling is unclear. We show
      that force prolongs lifetimes of single TCR-pMHC bonds for agonists (catch bonds)
      but shortens those for antagonists (slip bonds). Both magnitude and duration of
      force are important, as the highest Ca(2+) responses were induced by 10 pN via
      both pMHC catch bonds whose lifetime peaks at this force and anti-TCR slip bonds
      whose maximum lifetime occurs at 0 pN. High Ca(2+) levels require early and rapid
      accumulation of bond lifetimes, whereas short-lived bonds that slow early
      accumulation of lifetimes correspond to low Ca(2+) responses. Our data support a
      model in which force on the TCR induces signaling events depending on its
      magnitude, duration, frequency, and timing, such that agonists form catch bonds
      that trigger the T cell digitally, whereas antagonists form slip bonds that fail
      to activate.

PMID- 24725405
TI  - Mutant p53 drives pancreatic cancer metastasis through cell-autonomous PDGF
      receptor beta signaling.
AB  - Missense mutations in the p53 tumor suppressor inactivate its antiproliferative
      properties but can also promote metastasis through a gain-of-function activity.
      We show that sustained expression of mutant p53 is required to maintain the
      prometastatic phenotype of a murine model of pancreatic cancer, a highly
      metastatic disease that frequently displays p53 mutations. Transcriptional
      profiling and functional screening identified the platelet-derived growth factor
      receptor b (PDGFRb) as both necessary and sufficient to mediate these effects.
      Mutant p53 induced PDGFRb through a cell-autonomous mechanism involving
      inhibition of a p73/NF-Y complex that represses PDGFRb expression in p53
      deficient, noninvasive cells. Blocking PDGFRb signaling by RNA interference or by
      small molecule inhibitors prevented pancreatic cancer cell invasion in vitro and
      metastasis formation in vivo. Finally, high PDGFRb expression correlates with
      poor disease-free survival in pancreatic, colon, and ovarian cancer patients,
      implicating PDGFRb as a prognostic marker and possible target for attenuating
      metastasis in p53 mutant tumors.

PMID- 24725406
TI  - Antibiotic-induced replication stress triggers bacterial competence by increasing
      gene dosage near the origin.
AB  - Streptococcus pneumoniae (pneumococcus) kills nearly 1 million children annually,
      and the emergence of antibiotic-resistant strains poses a serious threat to human
      health. Because pneumococci can take up DNA from their environment by a process
      called competence, genes associated with antibiotic resistance can rapidly
      spread. Remarkably, competence is activated in response to several antibiotics.
      Here, we demonstrate that antibiotics targeting DNA replication cause an increase
      in the copy number of genes proximal to the origin of replication (oriC). As the
      genes required for competence initiation are located near oriC, competence is
      thereby activated. Transcriptome analyses show that antibiotics targeting DNA
      replication also upregulate origin-proximal gene expression in other bacteria.
      This mechanism is a direct, intrinsic consequence of replication fork stalling.
      Our data suggest that evolution has conserved the oriC-proximal location of
      important genes in bacteria to allow for a robust response to replication stress
      without the need for complex gene-regulatory pathways. PAPERCLIP:

PMID- 24725407
TI  - Structural basis of eukaryotic cell-cell fusion.
AB  - Cell-cell fusion proteins are essential in development. Here we show that the C.
      elegans cell-cell fusion protein EFF-1 is structurally homologous to viral class
      II fusion proteins. The 2.6 A crystal structure of the EFF-1 trimer displays the
      same 3D fold and quaternary conformation of postfusion class II viral fusion
      proteins, although it lacks a nonpolar "fusion loop," indicating that it does not
      insert into the target membrane. EFF-1 was previously shown to be required in
      both cells for fusion, and we show that blocking EFF-1 trimerization blocks the
      fusion reaction. Together, these data suggest that whereas membrane fusion driven
      by viral proteins entails leveraging of a nonpolar loop, EFF-1-driven fusion of
      cells entails trans-trimerization such that transmembrane segments anchored in
      the two opposing membranes are brought into contact at the tip of the EFF-1
      trimer to then, analogous to SNARE-mediated vesicle fusion, zip the two membranes
      into one.

PMID- 24725408
TI  - Asymmetric friction of nonmotor MAPs can lead to their directional motion in
      active microtubule networks.
AB  - Diverse cellular processes require microtubules to be organized into distinct
      structures, such as asters or bundles. Within these dynamic motifs, microtubule
      associated proteins (MAPs) are frequently under load, but how force modulates
      these proteins' function is poorly understood. Here, we combine optical trapping
      with TIRF-based microscopy to measure the force dependence of microtubule
      interaction for three nonmotor MAPs (NuMA, PRC1, and EB1) required for cell
      division. We find that frictional forces increase nonlinearly with MAP velocity
      across microtubules and depend on filament polarity, with NuMA's friction being
      lower when moving toward minus ends, EB1's lower toward plus ends, and PRC1's
      exhibiting no directional preference. Mathematical models predict, and
      experiments confirm, that MAPs with asymmetric friction can move directionally
      within actively moving microtubule pairs they crosslink. Our findings reveal how
      nonmotor MAPs can generate frictional resistance in dynamic cytoskeletal networks
      via micromechanical adaptations whose anisotropy may be optimized for MAP
      localization and function within cellular structures.

PMID- 24725409
TI  - Intestinal brush border assembly driven by protocadherin-based intermicrovillar
      adhesion.
AB  - Transporting epithelial cells build apical microvilli to increase membrane
      surface area and enhance absorptive capacity. The intestinal brush border
      provides an elaborate example with tightly packed microvilli that function in
      nutrient absorption and host defense. Although the brush border is essential for
      physiological homeostasis, its assembly is poorly understood. We found that brush
      border assembly is driven by the formation of Ca(2+)-dependent adhesion links
      between adjacent microvilli. Intermicrovillar links are composed of protocadherin
      24 and mucin-like protocadherin, which target to microvillar tips and interact to
      form a trans-heterophilic complex. The cytoplasmic domains of microvillar
      protocadherins interact with the scaffolding protein, harmonin, and myosin-7b,
      which promote localization to microvillar tips. Finally, a mouse model of Usher
      syndrome lacking harmonin exhibits microvillar protocadherin mislocalization and
      severe defects in brush border morphology. These data reveal an adhesion-based
      mechanism for brush border assembly and illuminate the basis of intestinal
      pathology in patients with Usher syndrome. PAPERFLICK:

PMID- 24725410
TI  - SWELL1, a plasma membrane protein, is an essential component of volume-regulated
      anion channel.
AB  - Maintenance of a constant cell volume in response to extracellular or
      intracellular osmotic changes is critical for cellular homeostasis. Activation of
      a ubiquitous volume-regulated anion channel (VRAC) plays a key role in this
      process; however, its molecular identity in vertebrates remains unknown. Here, we
      used a cell-based fluorescence assay and performed a genome-wide RNAi screen to
      find components of VRAC. We identified SWELL1 (LRRC8A), a member of a four
      transmembrane protein family with unknown function, as essential for hypotonicity
      induced iodide influx. SWELL1 is localized to the plasma membrane, and its
      knockdown dramatically reduces endogenous VRAC currents and regulatory cell
      volume decrease in various cell types. Furthermore, point mutations in SWELL1
      cause a significant change in VRAC anion selectivity, demonstrating that SWELL1
      is an essential VRAC component. These findings enable further molecular
      characterization of the VRAC channel complex and genetic studies for
      understanding the function of VRAC in normal physiology and disease.

PMID- 24725411
TI  - KRas localizes to the plasma membrane by spatial cycles of solubilization,
      trapping and vesicular transport.
AB  - KRas is a major proto-oncogene product whose signaling activity depends on its
      level of enrichment on the plasma membrane (PM). This PM localization relies on
      posttranslational prenylation for membrane affinity, while PM specificity has
      been attributed to electrostatic interactions between negatively charged
      phospholipids in the PM and basic amino-acids in the C terminus of KRas. By
      measuring kinetic parameters of KRas dynamics in living cells with a cellular
      automata-based data-fitting approach in realistic cell-geometries, we show that
      charge-based specificity is not sufficient to generate PM enrichment in light of
      the total surface area of endomembranes. Instead, mislocalized KRas is
      continuously sequestered from endomembranes by cytosolic PDEdelta to be unloaded
      in an Arl2-dependent manner to perinuclear membranes. Electrostatic interactions
      then trap KRas at the recycling endosome (RE), from where vesicular transport
      restores enrichment on the PM. This energy driven reaction-diffusion cycle
      explains how small molecule targeting of PDEdelta affects the spatial
      organization of KRas.

PMID- 24725412
TI  - Ribosomal protein s15 phosphorylation mediates LRRK2 neurodegeneration in
      Parkinson's disease.
AB  - Mutations in leucine-rich repeat kinase 2 (LRRK2) are a common cause of familial
      and sporadic Parkinson's disease (PD). Elevated LRRK2 kinase activity and
      neurodegeneration are linked, but the phosphosubstrate that connects LRRK2 kinase
      activity to neurodegeneration is not known. Here, we show that ribosomal protein
      s15 is a key pathogenic LRRK2 substrate in Drosophila and human neuron PD models.
      Phosphodeficient s15 carrying a threonine 136 to alanine substitution rescues
      dopamine neuron degeneration and age-related locomotor deficits in G2019S LRRK2
      transgenic Drosophila and substantially reduces G2019S LRRK2-mediated neurite
      loss and cell death in human dopamine and cortical neurons. Remarkably,
      pathogenic LRRK2 stimulates both cap-dependent and cap-independent mRNA
      translation and induces a bulk increase in protein synthesis in Drosophila, which
      can be prevented by phosphodeficient T136A s15. These results reveal a novel
      mechanism of PD pathogenesis linked to elevated LRRK2 kinase activity and
      aberrant protein synthesis in vivo.

PMID- 24725415
TI  - SnapShot: cancer vaccines.
AB  - This SnapShot illustrates the main concepts and underlying biology of therapeutic
      vaccination in cancer. Dendritic cells (DCs) are an essential component of
      vaccination through their capacity to capture, process, and present antigens to T
      cells. We have come a long way in our understanding of what is needed to elicit
      therapeutic immunity when cancer escapes the natural barrier of protective
      immunity. This progress enables the development of novel vaccines. 

PMID- 24725413
TI  - Activity-dependent p25 generation regulates synaptic plasticity and Abeta-induced
      cognitive impairment.
AB  - Cyclin-dependent kinase 5 regulates numerous neuronal functions with its
      activator, p35. Under neurotoxic conditions, p35 undergoes proteolytic cleavage
      to liberate p25, which has been implicated in various neurodegenerative diseases.
      Here, we show that p25 is generated following neuronal activity under
      physiological conditions in a GluN2B- and CaMKIIalpha-dependent manner. Moreover,
      we developed a knockin mouse model in which endogenous p35 is replaced with a
      calpain-resistant mutant p35 (Deltap35KI) to prevent p25 generation. The
      Deltap35KI mice exhibit impaired long-term depression and defective memory
      extinction, likely mediated through persistent GluA1 phosphorylation at Ser845.
      Finally, crossing the Deltap35KI mice with the 5XFAD mouse model of Alzheimer's
      disease (AD) resulted in an amelioration of beta-amyloid (Abeta)-induced synaptic
      depression and cognitive impairment. Together, these results reveal a
      physiological role of p25 production in synaptic plasticity and memory and
      provide new insights into the function of p25 in Abeta-associated neurotoxicity
      and AD-like pathology.

PMID- 24725416
TI  - Sweet taste loss in myasthenia gravis: more than a coincidence?
AB  - Sweet dysgeusia, a rare taste disorder, may be encountered in severe anti
      acetylcholine receptor antibody (AChRAb)-myasthenia gravis (MG). A 42 year-old
      man reported progressive loss of sweet taste evolving for almost 10 weeks,
      revealing an AChRAb-positive MG with thymoma. Improvement of sweet perception
      paralleled reduction of the MG composite score during the 15 months follow up
      period, with immunosuppressive and surgical treatments. We suggest that sweet
      dysgeusia is a non-motor manifestation of MG that may result from a thymoma
      dependent autoimmune mechanism targeting gustducin-positive G-protein-coupled
      taste receptor cells, in line with recent data from MRL/MpJ-Fas lpr/ (MRL/lpr)
      transgenic mice with autoimmune disease.

PMID- 24725417
TI  - Risk factors associated with toxoplasmosis and toxocariasis in populations of
      children from nine cities in southern Brazil.
AB  - This study investigated the epidemiological factors that contribute to the
      seroprevalence of Toxoplasma gondii and Toxocara spp. in children from Parana
      state, Brazil. Immunoglobulin G (IgG) antibodies to T. gondii were detected using
      indirect immunofluorescence, and IgG antibodies to Toxocara were detected using
      an enzyme-linked immunosorbent assay. For each individual, a questionnaire was
      completed that contained epidemiological and clinical data. The data analysis was
      performed using multiple logistic regression. Of the 544 children investigated,
      3.2% presented co-infection with T. gondii and Toxocara spp. Of this total, 7.4%
      were positive for antibodies to T. gondii, and 25% were positive for antibodies
      to Toxocara spp. The presence of antibodies to Toxocara spp. increased the risk
      of T. gondii infection (P = 0.029). Children who were 1-8 years of age were less
      infected by T. gondii than those who were 9-12 years of age. The variables that
      influenced positivity for anti-Toxocara spp. were the origin of the children and
      contact with sand. Children with positive serology for Toxocara spp. presented
      more eosinophilia compared with those with non-reactive serology. Infection with
      both parasites reveals the need for preventive measures, such as guidance about
      modes of infection, parasite control and monitoring recreational areas.

PMID- 24725414
TI  - Global analyses of human immune variation reveal baseline predictors of
      postvaccination responses.
AB  - A major goal of systems biology is the development of models that accurately
      predict responses to perturbation. Constructing such models requires the
      collection of dense measurements of system states, yet transformation of data
      into predictive constructs remains a challenge. To begin to model human immunity,
      we analyzed immune parameters in depth both at baseline and in response to
      influenza vaccination. Peripheral blood mononuclear cell transcriptomes, serum
      titers, cell subpopulation frequencies, and B cell responses were assessed in 63
      individuals before and after vaccination and were used to develop a systematic
      framework to dissect inter- and intra-individual variation and build predictive
      models of postvaccination antibody responses. Strikingly, independent of age and
      pre-existing antibody titers, accurate models could be constructed using pre
      perturbation cell populations alone, which were validated using independent
      baseline time points. Most of the parameters contributing to prediction
      delineated temporally stable baseline differences across individuals, raising the
      prospect of immune monitoring before intervention.

PMID- 24725418
TI  - Presence of growth hormone receptor (GH-R) mRNA and protein in goat ovarian
      follicles and improvement of in vitro preantral follicle survival and development
      with GH.
AB  - This study aimed to demonstrate the expression of growth hormone receptor (GH-R)
      mRNA and protein in goat ovarian follicles in order to investigate the effects of
      GH on the survival and development of preantral follicles. The ovaries were
      processed for the isolation of follicles to study GH-R mRNA expression or to
      localization of GH-R by immunohistochemical analysis. Pieces of ovarian cortex
      were cultured for 7 days in minimum essential medium(+) (MEM(+)) in the presence
      or absence of GH at different concentrations (1, 10, 50, 100, and 200 ng/mL).
      High expression levels of GH-R mRNA were observed in granulosa/theca cells from
      large antral follicles. However, preantral follicles do not express mRNA for GH
      R. Immunohistochemistry demonstrated that the GH-R protein was expressed in the
      oocytes/granulosa cells of antral follicles, but any protein expression was
      observed in preantral follicles. The highest (P < 0.05) rate of normal follicles
      and intermediate follicles was observed after 7 days in MEM(+) plus 10 ng/mL GH
      (70%). In conclusion, GH-R mRNA and protein are expressed in caprine antral
      follicles, but not in preantral follicles. Moreover, GH maintains the survival of
      goat preantral follicles and promotes the development of primordial follicles. 

PMID- 24725419
TI  - Effect of GnRH analogs in postnatal domestic cats.
AB  - The aim of this study was to reproductively assess the clinical and hormonal
      effects of a GnRH agonist (AG) and an antagonist (AN) administered during the
      postnatal period in domestic cats. Forty-eight male and female postnatal kittens
      were randomly assigned to deslorelin acetate 1.6 mg subcutaneous (AG; n = 16),
      acyline 33 MUg/100 g subcutaneous weekly for 3 months (AN; n = 16), or control
      (CO; n = 16) which remained untreated. The cats were followed up (behavioral
      observation, physical examination, fecal sexual steroid determinations, mating
      test, and pregnancy diagnosis) up to puberty. Puberty was delayed (weeks) in the
      AG animals (62.9 +/- 3.5; P < 0.01) but not in the AN (15.5 +/- 1.7; P > 0.05)
      when they were compared with CO kittens (13.4 +/- 0.4). Fifteen (15/16) of the AN
      and CO animals, and only 11 of 16 cats of the AG group were fertile (P > 0.1). No
      differences were found in body weight (P > 0.1) and measurements (P > 0.1),
      libido (P > 0.1) and in the appearance of side effects (P > 0.1; except a
      pyometra in an AG female) among groups. In both AG- and AN-treated males
      (testosterone; P < 0.01) and females (estradiol-17beta; P < 0.01) fecal hormone
      concentrations were lower than in CO group during the first five postnatal weeks
      but not later. It is concluded that the neonatal administration of these AG and
      AN decreased fecal sexual steroids during the first postnatal weeks causing, the
      agonists but not the antagonist, a significant, reversible delay in puberty
      appearance. 

PMID- 24725420
TI  - Changes in protein expression in testes of L2 strain Taiwan country chickens in
      response to acute heat stress.
AB  - Heat stress causes a decrease of fertility in roosters. Yet, the way acute heat
      stress affects protein expression remains poorly understood. This study
      investigated differential protein expression in testes of the L2 strain of Taiwan
      country chickens following acute heat stress. Twelve 45-week-old roosters were
      allocated into four groups, including control roosters kept at 25  degrees C,
      roosters subjected to 38  degrees C acute heat stress for 4 hours without
      recovery, with 2 hours of recovery, and with 6 hours of recovery. Testis samples
      were collected for morphologic assay and protein analysis. Some of the
      differentially expressed proteins were validated by Western blot and
      immunohistochemistry. Abnormal and apoptotic spermatogenic cells were observed at
      2 hours of recovery after acute heat stress, especially among the spermatocytes.
      Two-dimensional difference gel electrophoresis revealed that 119 protein spots
      were differentially expressed in chicken testes following heat stress, and
      peptide mass fingerprinting revealed that these spots contained 92 distinct
      proteins. In the heat-stressed samples, the heat shock proteins, chaperonin
      containing t-complex, and proteasome subunits were downregulated, and glutathione
      S-transferase, transgelin, and DJ-1 were upregulated. Our results demonstrate
      that acute heat stress impairs the processes of translation, protein folding, and
      protein degradation, and thus results in apoptosis and interferes with
      spermatogenesis. On the other hand, the increased expression of antioxidant
      enzymes, including glutathione S-transferase and DJ-1, may attenuate heat-induced
      damage. These findings may have implications for breeding chickens that can
      tolerate more extreme conditions. 

PMID- 24725421
TI  - Atopic dermatitis is a risk factor for intracorneal ring segment extrusion.

PMID- 24725422
TI  - Lumbar spinal stenosis: therapeutic options review.
AB  - Lumbar spinal stenosis (LSS) functionally impacts significant numbers of
      Americans per year. Current estimates place the number of Americans suffering
      from senescent lumbar spinal stenosis at 400,000. The prevalence of this disorder
      in patients ranging from 60 to 69 years of age is very high. Forty-seven percent
      of this age group have mild to moderate stenosis, and 19.7% have severe stenosis.
      As the baby boomer generation gets older, 10,000 individuals attain the age of 65
      years every day in United States. LSS is becoming very common and will be a major
      healthcare issue as the population ages. Although LSS is not life threatening, it
      can cause substantial disability with limitations to performing daily activities,
      and thus, the associated negative impact on quality of life (QOL). This article
      reviews the pathophysiology and current treatment options for LSS, focusing on
      evidence-based treatment options.

PMID- 24725423
TI  - New insight into the strategy for nitrogen metabolism in plant cells.
AB  - Nitrogen (N) is one of the most important mineral nutrients required by higher
      plants. Primary N absorbed by higher plants includes nitrate (NO3(-)), ammonium
      (NH4(+)), and organic N. Plants have developed several mechanisms for regulating
      their N metabolism in response to N availability and environmental conditions.
      Numerous transporters have been characterized and the mode of N movement within
      plants has been demonstrated. For further assimilation of N, various enzymes are
      involved in the key processes of NO3(-) or NH4(+) assimilation. N and carbon (C)
      metabolism are tightly coordinated in the fundamental biochemical pathway that
      permits plant growth. As N and C metabolism are the fundamental constituents of
      plant life, understanding N regulation is essential for growing plants and
      improving crop production. Regulation of N metabolism at the transcriptional and
      posttranscriptional levels provides important perceptions in the complex
      regulatory network of plants to adapt to changing N availability. In this
      chapter, recent advances in elucidating molecular mechanisms of N metabolism
      processes and regulation strategy, as well as interactions between C and N, are
      discussed. This review provides new insights into the strategy for studying N
      metabolism at the cellular level for optimum plant growth in different
      environments.

PMID- 24725424
TI  - Discoidin domain receptor functions in physiological and pathological conditions.
AB  - The discoidin domain receptors, DDR1 and DDR2, are nonintegrin collagen receptors
      that are members of the receptor tyrosine kinase family. Both DDRs bind a number
      of different collagen types and play important roles in embryo development.
      Dysregulated DDR function is associated with progression of various human
      diseases, including fibrosis, arthritis, and cancer. By interacting with key
      components of the extracellular matrix and displaying distinct activation
      kinetics, the DDRs form a unique subfamily of receptor tyrosine kinases. DDR
      facilitated cellular functions include cell migration, cell survival,
      proliferation, and differentiation, as well as remodeling of extracellular
      matrices. This review summarizes the current knowledge of DDR-ligand
      interactions, DDR-initiated signal pathways and the molecular mechanisms that
      regulate receptor function. Also discussed are the roles of DDRs in development
      and disease progression. 

PMID- 24725426
TI  - New insights into vertebrate skin regeneration.
AB  - Regeneration biology has experienced a renaissance as clinicians, scientists, and
      engineers have combined forces to drive the field of regenerative medicine.
      Studies investigating the mechanisms that regulate wound healing in adult mammals
      have led to a good understanding of the stereotypical processes that lead to
      scarring. Despite comparative studies of fetal wound healing in which no scar is
      produced, the fact remains that insights from this work have failed to produce
      therapies that can regenerate adult human skin. In this review, we analyze past
      and contemporary accounts of wound healing in a variety of vertebrates, namely,
      fish, amphibians, and mammals, in order to demonstrate how examples of skin
      regeneration in adult organisms can impact traditional wound-healing research.
      When considered together, these studies suggest that inflammation and
      reepithelialization are necessary events preceding both scarring and
      regeneration. However, the extent to which these processes may direct one outcome
      over another is likely weaker than currently accepted. In contrast, the extent to
      which newly deposited extracellular matrix in the wound bed can be remodeled into
      new skin, and the intrinsic ability of new epidermis to regenerate appendages,
      appears to underlie the divergence between scar-free healing and the persistence
      of a scar. We discuss several ideas that may offer areas of overlap between
      researchers using these different model organisms and which may be of benefit to
      the ultimate goal of scar-free human wound healing. 

PMID- 24725427
TI  - Mechanotransduction pathways linking the extracellular matrix to the nucleus.
AB  - Cells contain several mechanosensing components that transduce mechanical signals
      into biochemical cascades. During cell-ECM adhesion, a complex network of
      molecules mechanically couples the extracellular matrix (ECM), cytoskeleton, and
      nucleoskeleton. The network comprises transmembrane receptor proteins and focal
      adhesions, which link the ECM and cytoskeleton. Additionally, recently identified
      protein complexes extend this linkage to the nucleus by linking the cytoskeleton
      and the nucleoskeleton. Despite numerous studies in this field, due to the
      complexity of this network, our knowledge of the mechanisms of cell-ECM adhesion
      at the molecular level remains remarkably incomplete. Herein, we present a review
      of the structures of key molecules involved in cell-ECM adhesion, along with an
      evaluation of their predicted roles in mechanical sensing. Additionally, specific
      binding events prompted by force-induced conformational changes of each molecule
      are discussed. Finally, we propose a model for the biomechanical events prominent
      in cell-ECM adhesion. 

PMID- 24725425
TI  - New insights into the roles of Xin repeat-containing proteins in cardiac
      development, function, and disease.
AB  - Since the discovery of Xin repeat-containing proteins in 1996, the importance of
      Xin proteins in muscle development, function, regeneration, and disease has been
      continuously implicated. Most Xin proteins are localized to myotendinous
      junctions of the skeletal muscle and also to intercalated discs (ICDs) of the
      heart. The Xin gene is only found in vertebrates, which are characterized by a
      true chambered heart. This suggests that the evolutionary origin of the Xin gene
      may have played a key role in vertebrate origins. Diverse vertebrates including
      mammals possess two paralogous genes, Xinalpha (or Xirp1) and Xinbeta (or Xirp2),
      and this review focuses on the role of their encoded proteins in cardiac muscles.
      Complete loss of mouse Xinbeta (mXinbeta) results in the failure of forming ICD,
      severe growth retardation, and early postnatal lethality. Deletion of mouse
      Xinalpha (mXinalpha) leads to late-onset cardiomyopathy with conduction defects.
      Molecular studies have identified three classes of mXinalpha-interacting
      proteins: catenins, actin regulators/modulators, and ion-channel subunits. Thus,
      mXinalpha acts as a scaffolding protein modulating the N-cadherin-mediated
      adhesion and ion-channel surface expression. Xin expression is significantly
      upregulated in early stages of stressed hearts, whereas Xin expression is
      downregulated in failing hearts from various human cardiomyopathies. Thus,
      mutations in these Xin loci may lead to diverse cardiomyopathies and heart
      failure. 

PMID- 24725428
TI  - Formation and maintenance of the Golgi apparatus in plant cells.
AB  - The Golgi apparatus plays essential roles in intracellular trafficking, protein
      and lipid modification, and polysaccharide synthesis in eukaryotic cells. It is
      well known for its unique stacked structure, which is conserved among most
      eukaryotes. However, the mechanisms of biogenesis and maintenance of the
      structure, which are deeply related to ER-Golgi and intra-Golgi transport
      systems, have long been mysterious. Now having extremely powerful microscopic
      technologies developed for live-cell imaging, the plant Golgi apparatus provides
      an ideal system to resolve the question. The plant Golgi apparatus has unique
      features that are not conserved in other kingdoms, which will also give new
      insights into the Golgi functions in plant life. In this review, we will
      summarize the features of the plant Golgi apparatus and transport mechanisms
      around it, with a focus on recent advances in Golgi biogenesis by live imaging of
      plants cells. 

PMID- 24725429
TI  - Cell and molecular biology of septins.
AB  - Septins are a family of GTP-binding proteins that assemble into cytoskeletal
      filaments. Unlike other cytoskeletal components, septins form ordered arrays of
      defined stoichiometry that can polymerize into long filaments and bundle
      laterally. Septins associate directly with membranes and have been implicated in
      providing membrane stability and serving as diffusion barriers for membrane
      proteins. In addition, septins bind other proteins and have been shown to
      function as multimolecular scaffolds by recruiting components of signaling
      pathways. Remarkably, septins participate in a spectrum of cellular processes
      including cytokinesis, ciliogenesis, cell migration, polarity, and cell-pathogen
      interactions. Given their breadth of functions, it is not surprising that septin
      abnormalities have also been linked to human diseases. In this review, we discuss
      the current knowledge of septin structure, assembly and function, and discuss
      these in the context of human disease. 

PMID- 24725430
TI  - Vigilin interacts with CCCTC-binding factor (CTCF) and is involved in CTCF
      dependent regulation of the imprinted genes Igf2 and H19.
AB  - CCCTC-binding factor (CTCF), a highly conserved zinc finger protein, is a master
      organizer of genome spatial organization and has multiple functions in gene
      regulation. Mounting evidence indicates that CTCF regulates the imprinted genes
      Igf2 and H19 by organizing chromatin at the Igf2/H19 locus, although the
      mechanism by which CTCF carries out this function is not fully understood. By
      yeast two-hybrid screening, we identified vigilin, a multi-KH-domain protein, as
      a new partner of CTCF. Subsequent coimmunoprecipitation and glutathione S
      transferase pulldown experiments confirmed that vigilin interacts with CTCF.
      Moreover, vigilin is present at several known CTCF target sites, such as the
      promoter regions of c-myc and BRCA1, the locus control region of beta-globin, and
      several regions within the Igf2/H19 locus. In vivo depletion of vigilin did not
      affect CTCF binding; however, knockdown of CTCF reduced vigilin binding to the
      H19 imprinting control region. Furthermore, ectopic expression of vigilin
      significantly downregulated Igf2 and upregulated H19, whereas depletion of
      vigilin upregulated Igf2 and downregulated H19, in HepG2, CNE1 and HeLa cells.
      These results reveal the functional relevance of vigilin and CTCF, and show that
      the CTCF-vigilin complex contributes to regulation of Igf2/H19.

PMID- 24725431
TI  - Overcoming language barriers in community-based research with refugee and migrant
      populations: options for using bilingual workers.
AB  - BACKGROUND: Although the challenges of working with culturally and linguistically
      diverse groups can lead to the exclusion of some communities from research
      studies, cost effective strategies to encourage access and promote cross-cultural
      linkages between researchers and ethnic minority participants are essential to
      ensure their views are heard and their health needs identified. Using bilingual
      research assistants is one means to achieve this. In a study exploring alcohol
      and other drug service use by migrant women in Western Australia, bilingual
      workers were used to assist with participant recruitment and administration of a
      survey to 268 women who spoke more than 40 different languages. DISCUSSION:
      Professional interpreters, bilingual students, bilingual overseas-trained health
      professionals and community sector bilingual workers were used throughout the
      research project. For the initial qualitative phase, professional interpreters
      were used to conduct interviews and focus group sessions, however scheduling
      conflicts, inflexibility, their inability to help with recruitment and the
      expense prompted exploration of alternative options for interview interpreting in
      the quantitative component of the study. Bilingual mature-age students on work
      placement and overseas-trained health professionals provided good entry into
      their different community networks and successfully recruited and interviewed
      participants, often in languages with limited interpreter access. Although both
      groups required training and supervision, overseas-trained health professionals
      often had existing research skills, as well as understanding of key issues such
      as confidentiality and referral processes. Strategies to minimise social
      desirability bias and the need to set boundaries were discussed during regular
      debriefing sessions. Having a number of workers recruiting participants also
      helped minimise the potential for selection bias. The practical and educational
      experience gained by the bilingual workers was regarded as capacity building and
      a potentially valuable community resource for future health research projects.
      SUMMARY: The use of bilingual workers was key to the feasibility and success of
      the project. The most successful outcomes occurred with students and overseas
      trained health professionals who had good community networks for recruitment and
      the required linguistic skills. By describing the advantages and disadvantages
      encountered when working with bilingual workers, we offer practical insights to
      assist other researchers working with linguistically diverse groups.

PMID- 24725433
TI  - Dietary alpha-tocopherol and atorvastatin reduce high-fat-induced lipid
      accumulation and down-regulate CD36 protein in the liver of guinea pigs.
AB  - The increased uptake and storage of lipids in the liver are important features of
      steatotic liver diseases. The fatty acid translocase/scavenger receptor cluster
      of differentiation (CD)36 facilitates the hepatic uptake of lipids. We
      investigated if RRR-alpha-tocopherol (alphaT) alone or in combination with
      atorvastatin (ATV) is capable of preventing hepatic lipid accumulation via down
      regulation of CD36. To this end, Dunkin Hartley guinea pigs were fed a control
      diet (5% fat); or a high-fat control diet (21% fat, 0.15% cholesterol); or a high
      fat control diet fortified with alphaT (250 mg/kg diet), ATV (300 mg/kg diet) or
      both ATV+alphaT for 6 weeks. Hepatic triacylglycerols, hepatic protein and mRNA
      expression of CD36 as well as the mRNA expression of the controlling nuclear
      receptors LXRalpha, PXR and PPARgamma were determined. Animals fed the high-fat
      control diet accumulated significantly more triacylglycerols in the liver than
      control animals. This was significantly reduced by ATV and numerically by alphaT
      and ATV+alphaT. Hepatic CD36 protein concentrations were significantly higher in
      the high-fat than in the control group, and both alphaT and ATV reduced CD36
      expression to the level observed in the control group. However, no synergistic
      effect of the combined treatment was observed. Neither CD36 mRNA nor that of the
      nuclear receptors (LXRalpha, PXR and PPARgamma) differed between groups,
      suggesting a posttranslational regulatory mechanism. Our results indicate that
      orally administered ATV and alphaT individually, but not synergistically, prevent
      diet-induced lipid accumulation in the liver of guinea pigs by down-regulation of
      hepatic CD36 protein. 

PMID- 24725432
TI  - Chromium enhances insulin responsiveness via AMPK.
AB  - Trivalent chromium (Cr(3+)) is known to improve glucose homeostasis. Cr(3+) has
      been shown to improve plasma membrane-based aspects of glucose transporter GLUT4
      regulation and increase activity of the cellular energy sensor 5' AMP-activated
      protein kinase (AMPK). However, the mechanism(s) by which Cr(3+) improves insulin
      responsiveness and whether AMPK mediates this action is not known. In this study
      we tested if Cr(3+) protected against physiological hyperinsulinemia-induced
      plasma membrane cholesterol accumulation, cortical filamentous actin (F-actin)
      loss and insulin resistance in L6 skeletal muscle myotubes. In addition, we
      performed mechanistic studies to test our hypothesis that AMPK mediates the
      effects of Cr(3+) on GLUT4 and glucose transport regulation. Hyperinsulinemia
      induced insulin-resistant L6 myotubes displayed excess membrane cholesterol and
      diminished cortical F-actin essential for effective glucose transport regulation.
      These membrane and cytoskeletal abnormalities were associated with defects in
      insulin-stimulated GLUT4 translocation and glucose transport. Supplementing the
      culture medium with pharmacologically relevant doses of Cr(3+) in the picolinate
      form (CrPic) protected against membrane cholesterol accumulation, F-actin loss,
      GLUT4 dysregulation and glucose transport dysfunction. Insulin signaling was
      neither impaired by hyperinsulinemic conditions nor enhanced by CrPic, whereas
      CrPic increased AMPK signaling. Mechanistically, siRNA-mediated depletion of AMPK
      abolished the protective effects of CrPic against GLUT4 and glucose transport
      dysregulation. Together these findings suggest that the micronutrient Cr(3+), via
      increasing AMPK activity, positively impacts skeletal muscle cell insulin
      sensitivity and glucose transport regulation. 

PMID- 24725434
TI  - Space-time clusters of breast cancer using residential histories: a Danish case
      control study.
AB  - BACKGROUND: A large proportion of breast cancer cases are thought related to
      environmental factors. Identification of specific geographical areas with high
      risk (clusters) may give clues to potential environmental risk factors. The aim
      of this study was to investigate whether clusters of breast cancer existed in
      space and time in Denmark, using 33 years of residential histories. METHODS: We
      conducted a population-based case-control study of 3138 female cases from the
      Danish Cancer Registry, diagnosed with breast cancer in 2003 and two independent
      control groups of 3138 women each, randomly selected from the Civil Registration
      System. Residential addresses of cases and controls from 1971 to 2003 were
      collected from the Civil Registration System and geo-coded. Q-statistics were
      used to identify space-time clusters of breast cancer. All analyses were carried
      out with both control groups, and for 66% of the study population we also
      conducted analyses adjusted for individual reproductive factors and area-level
      socioeconomic indicators. RESULTS: In the crude analyses a cluster in the
      northern suburbs of Copenhagen was consistently found throughout the study period
      (1971-2003) with both control groups. When analyses were adjusted for individual
      reproductive factors and area-level socioeconomic indicators, the cluster area
      became smaller and less evident. CONCLUSIONS: The breast cancer cluster area that
      persisted after adjustment might be explained by factors that were not accounted
      for such as alcohol consumption and use of hormone replacement therapy. However,
      we cannot exclude environmental pollutants as a contributing cause, but no
      pollutants specific to this area seem obvious.

PMID- 24725435
TI  - Design, synthesis and pharmacological evaluation of novel polycyclic heteroarene
      ethers as PDE10A inhibitors: Part I.
AB  - We report analogue-based rational design and synthesis of two novel series of
      polycyclic heteroarenes, pyrrolo[3,2-b]quinolines and pyrido[2,3-b]indoles,
      tethered to a biaryl system by a methyl-, ethyl- or propyl ether as PDE10A
      inhibitors. A number of analogues were prepared with variable chain length and
      evaluated for their ability to block PDE10A enzyme using a radiometric assay.
      Detailed SAR analyses revealed that compounds with an ethyl ether linker are
      superior in potency compared to compounds with methyl or propyl ether linkers.
      These compounds, in general, showed poor metabolic stability in rat and human
      liver microsomes. The metabolic profile of one of the potent compounds was
      studied in detail to identify metabolic liabilities of these compounds.
      Structural modifications were carried out that resulted in improved metabolic
      stability without significant loss of potency.

PMID- 24725436
TI  - Characterization of single-stranded DNA-binding proteins from the psychrophilic
      bacteria Desulfotalea psychrophila, Flavobacterium psychrophilum, Psychrobacter
      arcticus, Psychrobacter cryohalolentis, Psychromonas ingrahamii, Psychroflexus
      torquis, and Photobacterium profundum.
AB  - BACKGROUND: Single-stranded DNA-binding proteins (SSBs) play essential roles in
      DNA replication, recombination and repair in Bacteria, Archaea and Eukarya. In
      recent years, there has been an increasing interest in SSBs, since they find
      numerous applications in diverse molecular biology and analytical methods.
      RESULTS: We report the characterization of single-stranded DNA-binding proteins
      from the psychrophilic bacteria Desulfotalea psychrophila (DpsSSB),
      Flavobacterium psychrophilum (FpsSSB), Psychrobacter arcticus (ParSSB),
      Psychrobacter cryohalolentis (PcrSSB), Psychromonas ingrahamii (PinSSB),
      Photobacterium profundum (PprSSB), and Psychroflexus torquis (PtoSSB). The
      proteins show a high differential within the molecular mass of their monomers and
      the length of their amino acid sequences. The high level of identity and
      similarity in respect to the EcoSSB is related to the OB-fold and some of the
      last amino acid residues. They are functional as homotetramers, with each monomer
      encoding one single stranded DNA binding domain (OB-fold). The fluorescence
      titrations indicated that the length of the ssDNA-binding site size is
      approximately 30 +/- 2 nucleotides for the PinSSB, 31 +/- 2 nucleotides for the
      DpsSSB, and 32 +/- 2 nucleotides for the ParSSB, PcrSSB, PprSSB and PtoSSB. They
      also demonstrated that it is salt independent. However, when the ionic strength
      was changed from low salt to high, binding-mode transition was observed for the
      FpsSSB, at 31 +/- 2 nucleotides and 45 +/- 2 nucleotides, respectively. As
      expected, the SSB proteins under study cause duplex DNA destabilization. The
      greatest decrease in duplex DNA melting temperature was observed in the presence
      of the PtoSSB 17  degrees C. The SSBs in question possess relatively high
      thermostability for proteins derived from cold-adapted bacteria. CONCLUSION: The
      results showed that SSB proteins from psychrophilic microorganisms are typical
      bacterial SSBs and possess relatively high thermostability, offering an
      attractive alternative to other thermostable SSBs in molecular biology
      applications.

PMID- 24725437
TI  - Simulations of pattern dynamics for reaction-diffusion systems via SIMULINK.
AB  - BACKGROUND: Investigation of the nonlinear pattern dynamics of a reaction
      diffusion system almost always requires numerical solution of the system's set of
      defining differential equations. Traditionally, this would be done by selecting
      an appropriate differential equation solver from a library of such solvers, then
      writing computer codes (in a programming language such as C or Matlab) to access
      the selected solver and display the integrated results as a function of space and
      time. This "code-based" approach is flexible and powerful, but requires a certain
      level of programming sophistication. A modern alternative is to use a graphical
      programming interface such as Simulink to construct a data-flow diagram by
      assembling and linking appropriate code blocks drawn from a library. The result
      is a visual representation of the inter-relationships between the state variables
      whose output can be made completely equivalent to the code-based solution.
      RESULTS: As a tutorial introduction, we first demonstrate application of the
      Simulink data-flow technique to the classical van der Pol nonlinear oscillator,
      and compare Matlab and Simulink coding approaches to solving the van der Pol
      ordinary differential equations. We then show how to introduce space (in one and
      two dimensions) by solving numerically the partial differential equations for two
      different reaction-diffusion systems: the well-known Brusselator chemical
      reactor, and a continuum model for a two-dimensional sheet of human cortex whose
      neurons are linked by both chemical and electrical (diffusive) synapses. We
      compare the relative performances of the Matlab and Simulink implementations.
      CONCLUSIONS: The pattern simulations by Simulink are in good agreement with
      theoretical predictions. Compared with traditional coding approaches, the
      Simulink block-diagram paradigm reduces the time and programming burden required
      to implement a solution for reaction-diffusion systems of equations. Construction
      of the block-diagram does not require high-level programming skills, and the
      graphical interface lends itself to easy modification and use by non-experts.

PMID- 24725438
TI  - Applications and implications of ecological energetics.
AB  - The ecological processes that are crucial to an animal's growth, survival, and
      reproductive fitness have energetic costs. The imperative for an animal to meet
      these costs within the energetic constraints of the environment drives many
      aspects of animal ecology and evolution, yet has largely been overlooked in
      traditional ecological paradigms. The field of 'ecological energetics' is
      bringing comparative physiology out of the laboratory and, for the first time, is
      becoming broadly accessible to field ecologists addressing real-world questions
      at many spatial and temporal scales. In an era of unprecedented global
      environmental challenges, ecological energetics opens up the tantalising prospect
      of a more predictive, mechanistic understanding of the drivers of threatened
      species decline, delivering process-based modelling approaches to natural
      resource management. 

PMID- 24725439
TI  - Muscle force depends on the amount of transversal muscle loading.
AB  - Skeletal muscles are embedded in an environment of other muscles, connective
      tissue, and bones, which may transfer transversal forces to the muscle tissue,
      thereby compressing it. In a recent study we demonstrated that transversal
      loading of a muscle with 1.3Ncm(-2) reduces maximum isometric force (Fim) and
      rate of force development by approximately 5% and 25%, respectively. The aim of
      the present study was to examine the influence of increasing transversal muscle
      loading on contraction dynamics. Therefore, we performed isometric experiments on
      rat M. gastrocnemius medialis (n=9) without and with five different transversal
      loads corresponding to increasing pressures of 1.3Ncm(-2) to 5.3Ncm(-2) at the
      contact area between muscle and load. Muscle loading was induced by a custom-made
      plunger which was able to move in transversal direction. Increasing transversal
      muscle loading resulted in an almost linear decrease in muscle force from 4.8+/
      1.8% to 12.8+/-2% Fim. Compared to an unloaded isometric contraction, rate of
      force development decreased from 20.2+/-4.0% at 1.3Ncm(-2) muscle loading to
      34.6+/-5.7% at 5.3Ncm(-2). Experimental observation of the impact of transversal
      muscle loading on contraction dynamics may help to better understand muscle
      tissue properties. Moreover, applying transversal loads to muscles opens a window
      to analyze three-dimensional muscle force generation. Data presented in this
      study may be important to develop and validate muscle models which enable
      simulation of muscle contractions under compression and enlighten the mechanisms
      behind. 

PMID- 24725440
TI  - Mechanical characterisation of porcine rectus sheath under uniaxial and biaxial
      tension.
AB  - Incisional hernia development is a significant complication after laparoscopic
      abdominal surgery. Intra-abdominal pressure (IAP) is known to initiate the
      extrusion of intestines through the abdominal wall, but there is limited data on
      the mechanics of IAP generation and the structural properties of rectus sheath.
      This paper presents an explanation of the mechanics of IAP development, a study
      of the uniaxial and biaxial tensile properties of porcine rectus sheath, and a
      simple computational investigation of the tissue. Analysis using Laplace's law
      showed a circumferential stress in the abdominal wall of approx. 1.1MPa due to an
      IAP of 11kPa, commonly seen during coughing. Uniaxial and biaxial tensile tests
      were conducted on samples of porcine rectus sheath to characterise the stress
      stretch responses of the tissue. Under uniaxial tension, fibre direction samples
      failed on average at a stress of 4.5MPa at a stretch of 1.07 while cross-fibre
      samples failed at a stress of 1.6MPa under a stretch of 1.29. Under equi-biaxial
      tension, failure occurred at 1.6MPa with the fibre direction stretching to only
      1.02 while the cross-fibre direction stretched to 1.13. Uniaxial and biaxial
      stress-stretch plots are presented allowing detailed modelling of the tissue
      either in silico or in a surrogate material. An FeBio computational model of the
      tissue is presented using a combination of an Ogden and an exponential power law
      model to represent the matrix and fibres respectively. The structural properties
      of porcine rectus sheath have been characterised and add to the small set of
      human data in the literature with which it may be possible to develop methods to
      reduce the incidence of incisional hernia development. 

PMID- 24725441
TI  - Development and validation of a bioreactor system for dynamic loading and
      mechanical characterization of whole human intervertebral discs in organ culture.
AB  - Intervertebral disc (IVD) degeneration is a common cause of back pain, and
      attempts to develop therapies are frustrated by lack of model systems that mimic
      the human condition. Human IVD organ culture models can address this gap, yet
      current models are limited since vertebral endplates are removed to maintain cell
      viability, physiological loading is not applied, and mechanical behaviors are not
      measured. This study aimed to (i) establish a method for isolating human IVDs
      from autopsy with intact vertebral endplates, and (ii) develop and validate an
      organ culture loading system for human or bovine IVDs. Human IVDs with intact
      endplates were isolated from cadavers within 48h of death and cultured for up to
      21 days. IVDs remained viable with ~80% cell viability in nucleus and annulus
      regions. A dynamic loading system was designed and built with the capacity to
      culture 9 bovine or 6 human IVDs simultaneously while applying simulated
      physiologic loads (maximum force: 4kN) and measuring IVD mechanical behaviors.
      The loading system accurately applied dynamic loading regimes (RMS error <2.5N
      and total harmonic distortion <2.45%), and precisely evaluated mechanical
      behavior of rubber and bovine IVDs. Bovine IVDs maintained their mechanical
      behavior and retained >85% viable cells throughout the 3 week culture period.
      This organ culture loading system can closely mimic physiological conditions and
      be used to investigate response of living human and bovine IVDs to mechanical and
      chemical challenges and to screen therapeutic repair techniques. 

PMID- 24725442
TI  - Safety, tolerability, pharmacokinetics, and pharmacodynamics of multiple doses of
      apixaban in healthy Japanese male subjects.
AB  - OBJECTIVE: This was a randomized, placebo-controlled, double-blind, sequential,
      ascending-dose study to assess the safety, tolerability, pharmacokinetics, and
      pharmacodynamics of multiple oral doses of apixaban in healthy Japanese male
      subjects. METHODS: The study was conducted using three sequential dose panels:
      apixaban 2.5 mg, 5 mg, and 10 mg given twice daily. For each dose panel, subjects
      were randomly assigned to receive oral apixaban (n = 6) or matching placebo (n =
      2) for 7 days. The pharmacokinetics of apixaban and effect on pharmacodynamic
      variables (clotting assays and anti-Xa activity) were assessed on day 1 and day 7
      of treatment. Safety was assessed throughout the study. Only after the preceding
      dose was confirmed to be safe and well-tolerated subjects were enrolled into the
      next-higher-dose panel. RESULTS: Apixaban was safe and well-tolerated in these
      healthy Japanese male subjects across the doses evaluated. On day 7, peak plasma
      concentrations were reached ~ 3 hours postdose, and increases in peak plasma
      concentration (C(max)), trough plasma concentration, and area under the plasma
      concentration-time curve across one dosing interval (12 hours) were tested dose
      proportional across the dose range. A modest degree of accumulation was observed
      that was similar for all doses (accumulation index of 1.7 to 2.0), and renal
      clearance was consistent across doses (0.91 L/h - 1.07 L/h). Exposure-dependent
      prolongation of prothrombin time, activated partial thromboplastin time, modified
      prothrombin time, and increases in anti-Xa activity were observed after single
      and multiple doses of apixaban. CONCLUSIONS: Apixaban was safe and well-tolerated
      in healthy Japanese subjects. The pharmacokinetic profile of apixaban following
      multiple twice-daily doses was linear, and exposure parameters such as C(max),
      observed at ~ 3 hours post-dose, and area under the plasma concentration-time
      curve increased in a dose-proportional manner. Pharmacodynamic profiles closely
      followed the apixaban plasma concentration-time profiles.

PMID- 24725443
TI  - Filgrastim use in the emergency department of a Spanish general hospital.
AB  - BACKGROUND: Febrile neutropenia is a cause of dose reduction in hematological
      cancer treatments, with patient risk of infection proportional to duration and
      severity. In addition, colony-stimulating factors have been shown to be
      beneficial in a patient subgroup, although they are probably overused in the
      clinical setting. OBJECTIVE: Evaluation of compliance with American Society of
      Clinical Oncology 2006 criteria when it comes to filgrastim use in the Emergency
      Department of a Spanish general hospital. METHODS AND MATERIALS: A prospective
      observational study from August 2011 to February 2012 in a tertiary Spanish
      General Hospital. We included all patients prescribed with filgrastim in the
      Emergency Department. Data was collected on demographics, the pharmacotherapy
      history, the administered chemoprophylaxis, and the destination after discharge
      from a clinical department, the complete blood count, and the presence of fever
      >= 38  degrees C. RESULTS: 51 patients were recorded over the period of the
      study. 27.45% of prescriptions complied with the clinical practice guideline
      criteria given the risk of febrile neutropenia, whereas 72.34% of prescriptions
      did not comply with the criteria, 17.65% of which did not fulfil any
      requirements. CONCLUSIONS: A high percentage of colony-stimulating factors use in
      the Emergency Department does not comply with the medical practice guideline.

PMID- 24725444
TI  - Implications of choosing a correlation structure on model selection and parameter
      estimation.
AB  - The purpose of this research was to evaluate implications of choosing a
      statistical or biological correlation structure on model selection and parameter
      estimation. were performed with and without biological (weight as a common
      covariate) or statistical (off diagonal element in omega matrix) correlation
      between clearance (CL) and volume of distribution (Vd). One-compartment model
      with IV bolus administration was used with 30% interindividual variability (%CV)
      on CL and Vd. The results were compared for model selection, parameter
      equivalence, bias, and imprecision. We found that estimation of fixed-effect
      parameters (CL, Vd) was robust and estimates of random-effect parameters were not
      influenced by inclusion or exclusion of statistical correlation irrespective of
      true correlation structure. However, CVCL and CVV were inflated (by 18 - 35%)
      when true biological correlation was ignored or accounted for by statistical
      correlation. It is important to note that in spite of the inflated estimates;
      these values represent the true variability in the simulated dataset, i.e.,
      reflecting the random variance plus the variance associated with weight.
      Therefore, if statistical correlation was used in absence of true covariate
      information, the range of individual parameters in future simulations would be
      similar compared to a model that uses true biological correlation. A true
      correlation structure is unknown for real life examples; a statistical
      correlation is a suitable alternative. 

PMID- 24725445
TI  - Pharmacokinetics and bioequivalence study of irbesartan tablets after a single
      oral dose of 300 mg in healthy Thai volunteers.
AB  - OBJECTIVE: Pharmacokinetics and bioequivalence of 300 mg irbesartan tablets were
      studied in 26 healthy Thai male volunteers. METHODS: A single oral dose of one
      300 mg tablet of the test product and the reference product was given to each
      volunteer according to a randomized two-way crossover design with 1-week wash out
      period. Blood samples were collected at predetermined time intervals until 72
      hours post dose and irbesartan concentration was quantified with a validated HPLC
      method. Individual plasma irbesartan concentration-time profile was analyzed for
      pharmacokinetic parameters. RESULTS: Maximum plasma concentrations (Cmax) of
      3,617.19 and 3,295.77 ng/mL for test and reference, respectively, were achieved.
      Areas under the plasma concentration-time curve; AUC0-t and AUC0-infinity were
      15,304.65 and 15,638.90 ng*h/mL for test and 15,389.21 and 15,730.34 ng*h/mL for
      reference. The median tmax was 1.50 hours and 1.25 hours for test and reference,
      respectively. Plasma elimination half-lives (t1/2) were 7.35 hours and 8.09 hours
      for test and reference, respectively. Primary pharmacokinetic parameters Cmax,
      AUC0-t, and AUC0-infinity were tested parametrically by analysis of variance
      (ANOVA), and it revealed no statistically significant difference (defined as p <
      0.05) between the corresponding Cmax, AUC0-t, and AUC0-infinity with respect to
      sequence, volunteers, period and formulation. The 90% confidence intervals for
      the ratio of test and reference product of the parameters Cmax, AUC0-t, and AUC0
      infinity were within 80 - 125% (100.13 - 121.40% for Cmax, 90.83 - 106.86% for
      AUC0-t and 91.11 - 106.55% for AUC0-infinity). CONCLUSION: The two products were
      bioequivalent in terms of both rate and extent of drug absorption into systemic
      circulation.

PMID- 24725446
TI  - Comparison of diagnostic potential of serological, molecular and cell culture
      methods for detection of Q fever in ruminants.
AB  - Q fever is an infectious disease caused by Coxiella burnetii. Diagnosis of Q
      fever based on clinical symptoms is unattainable; thus, different laboratory
      techniques are used to detect the infection. The aim of the study was to compare
      the diagnostic potential of ELISA, CFT, conventional PCR, real-time PCR and cell
      culture. The tests were carried out on 2251 serum samples from ruminants.
      Moreover, 668 placentas, 1277 vaginal swabs and 306 specimens of the internal
      organs of aborted foetuses were examined by PCR and cell culture. Pearson's chi
      square test was used to compare the results obtained by ELISA, CFT, PCR, real
      time PCR and isolation in cell culture. The chi(2) test confirmed that in most
      cases the results obtained by means of the different methods were correlated with
      each other (P<0.05). The highest correlation coefficients (r=0.76-0.87) were
      observed in the case of real-time PCR and conventional PCR. ELISA and CFT were
      moderately correlated (r=0.43-0.45). When the comparison was made between the
      results of tests run on samples from swabs and aborted foetuses, the r values
      between ELISA and CFT were lower than those between ELISA and PCRs. A negligible,
      or weak to moderate relationship was mostly observed when the method of cell
      culture isolation was compared with all the other analytical techniques
      investigated. The use of a combination of different laboratory methods,
      preferably ELISA for serology and polymerase chain reactions for the agent
      detection, is suggested to achieve the correct diagnosis of Q fever. 

PMID- 24725447
TI  - Identification of novel bovine group A rotavirus G15P[14] strain from epizootic
      diarrhea of adult cows by de novo sequencing using a next-generation sequencer.
AB  - There are few reports describing diarrhea of adult cattle caused by group A
      rotaviruses. Here, we report the identification of a novel bovine group A
      rotavirus from diarrhea of adult cows. A group A rotavirus was detected from an
      epizootic outbreak of diarrhea in adult cows with a decrease in milk production
      in Japan in 2013. The comprehensive genomic analyses from fecal samples by viral
      metagenomics using a next-generation sequencer revealed that it had an unreported
      genotype combination G15P[14]. The genome constellation of this strain, namely,
      RVA/Cow-wt/JPN/Tottori-SG/2013/G15P[14] was G15-P[14]-I2-R2-C2-M2-A3-N2-T6-E2-H3
      representing VP7-VP4-VP6-VP1-VP2-VP3-NSP1-NSP2-NSP3-NSP4-NSP5, respectively. Each
      gene segment of Tottori-SG was most closely related to Japanese bovine group A
      rotaviruses suggesting that Tottori-SG might have derived from multiple
      reassortment events from group A rotavirus strains circulating among Japanese
      cattle. No other diarrhea pathogen of adult cattle was detected by routine
      diagnosis and metagenomics. Viral metagenomics, using a next-generation
      sequencer, is useful to characterize group A rotaviruses from fecal samples and
      offers unbiased comprehensive investigations of pathogen. 

PMID- 24725448
TI  - Detection of bovine herpesvirus 2 and bovine herpesvirus 4 DNA in trigeminal
      ganglia of naturally infected cattle by polymerase chain reaction.
AB  - Establishment of latent infection within specific tissues in the host is a common
      biological feature of the herpesviruses. In the case of bovine herpesvirus 2
      (BoHV-2), latency is established in neuronal tissues, while bovine herpesvirus 4
      (BoHV-4) and ovine herpesvirus 2 (OvHV-2) latent virus targets on cells of the
      monocytic lineage. This study was conducted in quest of BoHV-2, BoHV-4 and OvHV-2
      DNA in two hundred trigeminal ganglia (TG) specimens, derived from one hundred
      clinically healthy cattle, majority of them naturally infected with bovine
      herpesvirus 1 (BoHV-1) and bovine herpesvirus 5 (BoHV-5). Total DNA extracted
      from ganglia was analyzed by polymerase chain reaction (PCR) designed to amplify
      part of the genes coding for BoHV-2, and BoHV-4 glycoprotein B and, for OvHV-2,
      the gene coding for phosphoribosylformylglycinamidine synthase-like protein. BoHV
      2 DNA was detected in TG samples of two (2%) and BoHV-4 DNA in nine (9%) of the
      animals, whereas OvHV-2 DNA could not be detected in any of the TG DNA. The two
      animals in which BoHV-2 DNA was identified were also co-infected with BoHV-1 and
      BoHV-5. Within the nine animals in which BoHV-4 DNA was detected, six were also
      co-infected with BoHV-1 and BoHV-5. This report provides for the first time
      evidence that viral DNA from BoHV-2 and BoHV-4 can be occasionally detected in TG
      of naturally infected cattle. Likewise, in this report we provided for the first
      time evidence that the co-infection of cattle with three distinct bovine
      herpesviruses might be a naturally occurring phenomenon. 

PMID- 24725449
TI  - Identification of Treponema pedis as the predominant Treponema species in porcine
      skin ulcers by fluorescence in situ hybridization and high-throughput sequencing.
AB  - Skin lesions often seen in pig production are of great animal welfare concern. To
      study the potential role of Treponema bacteria in porcine skin ulcers, we
      investigated the presence and distribution of these organisms in decubital
      shoulder ulcers (n=51) and ear necroses (n=54) by fluorescence in situ
      hybridization (FISH) and high-throughput sequencing. In addition, two cases of
      facial ulcers and five cases of other skin ulcers were included in the study.
      Samples from all 112 skin lesions and intact skin from pigs without skin ulcers
      (n=14) were screened by FISH. Three different oligonucleotide probes targeting
      16S rRNA were used, specific for domain bacterium, Treponema spp. and species T.
      pedis. Screening showed that two cases each of facial and other ulcers, 35 (69%)
      of shoulder ulcers and 32 (59%) of ear necroses were positive for Treponema spp.
      T. pedis was the unequivocally, predominant species typically constituting more
      than 90% of the treponemes in a lesion, assessed visually by microscopy.
      Altogether, T. pedis was demonstrated in 69 of the 71 Treponema spp. positive
      lesions. We conclude that Treponema spp. are frequently present and abundant in
      various skin ulcers of pigs. The results from this study point toward an
      important role of T. pedis as a secondary bacterial infection in porcine skin
      ulcers, especially in severe and chronic lesions. 

PMID- 24725451
TI  - Portrait, treatment choices and management of breast cancer in nonagenarians: an
      ongoing challenge.
AB  - There are only scarce data on the management of nonagenarians with breast cancer,
      and more particularly on the place of radiation therapy (RT). We report a
      retrospective study on patients aged 90 years old or older, with breast cancer,
      receiving RT. Records from RT departments from five institutions were reviewed to
      identify patients 90 years old of age and older undergoing RT over past decade
      for breast cancer. Tumors' characteristics were examined, as well treatment
      specificities and treatment intent. 44 patients receiving RT courses were
      identified, mean age 92 years. Treatment was given with curative and palliative
      intent in 72.7% and 27.3% respectively. Factors associated with a curative
      treatment were performance status (PS), place of life, previous surgery, and
      tumor stage. Median total prescribed dose was 40 Gy (23-66). Hypo fractionation
      was used in 77%. Most toxicities were mild to moderate. RT could not be completed
      in 1 patient (2.3%). No long-term toxicity was reported. Among 31 patients
      analyzable for effectiveness, 24 patients (77.4%) had their diseased controlled
      until last follow-up, including 17 patients (54.8%) experiencing complete
      response. At last follow-up, 4 patients (12.9%) were deceased, cancer being cause
      of death for two of them. The study shows that breast/chest RT is feasible in
      nonagenarians. Although the definitive benefit of RT could not be addressed here,
      hypofractionated therapy allowed a good local control with acceptable side
      effects. 

PMID- 24725452
TI  - Multicystic encephalopathy in abusive head trauma.
AB  - OBJECTIVE: The proof of abusive head trauma (AHT) in infants is difficult,
      especially in cases with a long posttraumatic survival period. In the acute
      phase, injury to the cranio-cervical junction causes disturbances in respiratory
      and cardiac control, leading to apnea and bradycardia. Infants who survive the
      acute phase may subsequently develop multicystic encephalopathy. Because some
      types of changes are age-dependent, examination of the patterns of brain damage
      in these cases could provide information about the time in which they were
      inflicted. In particular, this could apply to the extent of the cystic changes,
      namely that the severity thereof may decrease with older age upon infliction of
      the trauma. This could potentially date the injury and thereby help to identify
      the perpetrator. We present an analysis of the patterns of brain damage in cases
      of AHT-induced multicystic encephalopathy and comment on the possible etiology
      and the implications thereof. MATERIALS: Nine archival cases of trauma-induced
      multicystic encephalopathy, originating between the years 2005 and 2011, were
      identified. In 8 of these cases, hematoxilin-eosin-stained whole-hemisphere
      histologic slides, as well as small histologic slides of cerebellar hemispheres,
      were available for the evaluation of the topographic distribution of the
      macroscopic and microscopic changes. RESULTS: The cerebral hemispheres were more
      affected than the cerebellum. The magnitude of the cystic changes did not
      correlate with the age at which the trauma had occurred, nor the surviva period.
      All cases showed asymmetrical affection of the cerebral hemispheres, which in 3
      cases was very pronounced. The analysis revealed both ischemia- and hypoperfusion
      induced injury patterns. CONCLUSION: Analysis of the magnitude and the
      distribution of the damage do not assist in the estimation of the period at which
      the trauma had occurred. The evaluation showed that ischemia, and to a lesser
      extent, hypoperfusion, were the major mechanisms of brain injury in these cases,
      which does not narrow the differential diagnosis of the underlying problem.
      However, in cases of multicystic encephalopathy, in the absence of a plausible
      medical explanation for the development of this condition, a remote (abusive)
      head trauma should be considered.

PMID- 24725450
TI  - Conformational changes and translocation of tissue-transglutaminase to the plasma
      membranes: role in cancer cell migration.
AB  - BACKGROUND: Tissue-transglutaminase (TG2), a dual function G-protein, plays key
      roles in cell differentiation and migration. In our previous studies we reported
      the mechanism of TG2-induced cell differentiation. In present study, we explored
      the mechanism of how TG2 may be involved in cell migration. METHODS: To study the
      mechanism of TG2-mediated cell migration, we used neuroblastoma cells (SH-SY5Y)
      which do not express TG2, neuroblastoma cells expressing exogenous TG2 (SHYTG2),
      and pancreatic cancer cells which express high levels of endogenous TG2.
      Resveratrol, a natural compound previously shown to inhibit neuroblastoma and
      pancreatic cancer in the animal models, was utilized to investigate the role of
      TG2 in cancer cell migration. Immunofluorescence assays were employed to detect
      expression and intracellular localization of TG2, and calcium levels in the
      migrating cells. Native gel electrophoresis was performed to analyze resveratrol
      induced cellular distribution and conformational states of TG2 in migrating
      cells. Data are presented as the mean and standard deviation of at least 3
      independent experiments. Comparisons were made among groups using one-way ANOVA
      followed by Tukey-Kramer ad hoc test. RESULTS: TG2 containing cells (SHYTG2 and
      pancreatic cancer cells) exhibit increased cell migration and invasion in
      collagen-coated and matrigel-coated transwell plate assays, respectively.
      Resveratrol (1 MUM-10 MUM) prevented migration of TG2-expressing cells. During
      the course of migration, resveratrol increased the immunoreactivity of TG2
      without affecting the total TG2 protein level in migrating cells. In these cells,
      resveratrol increased calcium levels, and depletion of intracellular calcium by a
      calcium chelator, BAPTA, attenuated resveratrol-enhanced TG2 immunoreactivity. In
      native-polyacrylamide gels, we detected an additional TG2 protein band with
      slower migration in total cell lysates of resveratrol treated cells. This TG2
      form is non-phosphorylated, exclusively present in plasma membrane fractions and
      sensitive to intracellular Ca(2+) concentration suggesting a calcium requirement
      in TG2-regulated cell migration. CONCLUSIONS: Taken together, we conclude that
      resveratrol induces conformational changes in TG2, and that Ca(2+)-mediated TG2
      association with the plasma membrane is responsible for the inhibitory effects of
      resveratrol on cell migration.

PMID- 24725453
TI  - Primary central nervous system lymphoma: current state of anti-CD20 therapy and
      appraisal of reported response criteria.
AB  - Primary central nervous system lymphoma (PCNSL) is an aggressive non-Hodgkin's
      lymphoma which is confined to the central nervous system and may also affect
      intraocular structures. Despite high initial rates of response to methotrexate
      based chemotherapy, more than 50% of patients will experience relapse and about
      10% have disease that is refractory to chemotherapy. Outcome in patients who fail
      treatment is very poor, and therefore new therapeutic approaches that may
      increase the rate of complete response and the proportion of durable remission
      are sought. Based on the pivotal role that anti-CD20 therapy now plays in the
      treatment outcome of aggressive systemic B-cell lymphomas, a similar approach is
      commonly being adapted for PCNSL despite the lack of evidence for its
      effectiveness. This review examines the current status and level of evidence for
      the use of monoclonal antibodies against the CD20 surface antigen, which is
      present on normal and malignant B-cells in PCNSL. The review covers both systemic
      and local (intracerebrospinal fluid or intravitreal) administration of CD20
      monoclonal antibodies in PCNSL. In addition, it scrutinizes the response criteria
      commonly reported for evaluation of treatment outcome. The importance of
      differentiating unconfirmed complete response from partial response is outlined
      and the lack of consensus on response criteria for atypical imaging presentations
      of PCNSL is delineated.

PMID- 24725454
TI  - Aquatic ecology of the oyster pathogens Vibrio splendidus and Vibrio
      aestuarianus.
AB  - The ecology of the oyster pathogens Vibrio splendidus and Vibrio aestuarianus in
      the brackish aquatic environment was extensively investigated in this study. By
      conducting laboratory experiments under natural setting conditions, it was shown
      that V. splendidus LGP32 strain generally exhibits longer persistence in both
      seawater and sediment than V. aestuarianus 01/32 strain. Both strains maintained
      viability and culturability for longer times in the sediment, suggesting that
      this compartment may represent a suitable niche for their persistence in the
      environment. In addition, both strains attached to chitin particles and copepods,
      the efficiency of attachment being higher in V. splendidus than in V.
      aestuarianus. Similarly, LGP32 strain showed a greater capability to form biofilm
      on poly-vinyl chloride (PVC) surfaces than 01/32 strain. LGP32 and 01/32 strains
      were also capable of entering a viable but non-culturable state after extended
      incubation at 5 degrees C, a condition commonly found during cold season in the
      aquatic brackish environment. These results are consistent with field data
      collected during a 2-year sampling campaign in the northern Adriatic Sea and
      provide background information on the mechanisms promoting V. splendidus and V.
      aestuarianus persistence in coastal water, thus contributing to a better
      understanding of the epidemiology of the associated diseases. 

PMID- 24725455
TI  - Ethnicity and age at onset in bipolar spectrum disorders.
AB  - IntroductionTo determine the influence of ethnicity on the age at onset (AAO) and
      further understand the significance of AAO as a clinical marker of bipolar and
      schizoaffective disorders. METHODS: Admixture analysis was used to identify sub
      groups characterized by differences in AAO. Differences in clinical features were
      analyzed for these sub-groups using multivariate logistic regression. Comparisons
      were made with previous studies using the 2-Sample Kolmogorov-Smirnov Test.
      RESULTS: Admixture analysis yielded a combination of 2 normal theoretical
      distributions with means (SD) of 16.9 (3.6) for the early-onset sub-group and
      24.4 (9.2) years for the late-onset sub-group. The sub-groups were divided by a
      cut-off of 22 years. There were significant differences between the early and
      late onset bipolar patient populations regarding substance abuse comorbidity
      (P=.044) and psychotic features (P=.015). Ethnicity did not have a significant
      influence on the AAO.DiscussionThe associations between early-onset and higher
      incidence of psychosis and substance abuse in our sample are consistent with
      other studies exploring the AAO in bipolar disorder. CONCLUSION: Our findings
      support the notion of AAO as a clinical marker for the underlying heterogeneity
      of bipolar spectrum disorders. In particular, we found a strong overlap of early
      AAO with clinical features associated with greater severity and poor outcome.

PMID- 24725456
TI  - Marked Response to VNS in a Post-Cingulotomy Patient: Implications for the
      Mechanism of Action of VNS in TRD.
AB  - Treatment-resistant major depression (TRMD, major depressive disorder that fails
      to respond to numerous therapies) is a relatively common and clinically
      challenging disorder. In many cases, the most severely affected TRMD patients
      have received surgical intervention (subcaudate tractotomy, limbic leucotomy,
      anterior capsulotomy, and anterior cingulotomy). New treatments, including vagus
      nerve stimulation (VNS) and deep brain stimulation, have emerged to treat
      individuals with TRMD. We describe the case of a woman, 53 years of age, with a
      long and sustained history of TRMD (33 years), which was unresponsive to numerous
      treatments (multiple pharmacotherapies, psychotherapy, electroconvulsive therapy
      [ECT]). Additionally, her TRMD failed to respond to a bilateral anterior
      cingulotomy. She underwent placement of a cervical vagus nerve stimulator and a
      brief course of ECT (3 unilateral treatments). Her depression improved markedly,
      and it has remained in sustained remission for 3.5 years. This case suggests a
      potential synergistic effect of VNS and ECT, as well as provides possible clues
      to the neural circuitry of VNS in TRMD. 

PMID- 24725458
TI  - Impact of cultivar selection and process optimization on ethanol yield from
      different varieties of sugarcane.
AB  - BACKGROUND: The development of 'energycane' varieties of sugarcane is underway,
      targeting the use of both sugar juice and bagasse for ethanol production. The
      current study evaluated a selection of such 'energycane' cultivars for the
      combined ethanol yields from juice and bagasse, by optimization of dilute acid
      pretreatment optimization of bagasse for sugar yields. METHOD: A central
      composite design under response surface methodology was used to investigate the
      effects of dilute acid pretreatment parameters followed by enzymatic hydrolysis
      on the combined sugar yield of bagasse samples. The pressed slurry generated from
      optimum pretreatment conditions (maximum combined sugar yield) was used as the
      substrate during batch and fed-batch simultaneous saccharification and
      fermentation (SSF) processes at different solid loadings and enzyme dosages,
      aiming to reach an ethanol concentration of at least 40 g/L. RESULTS: Significant
      variations were observed in sugar yields (xylose, glucose and combined sugar
      yield) from pretreatment-hydrolysis of bagasse from different cultivars of
      sugarcane. Up to 33% difference in combined sugar yield between best performing
      varieties and industrial bagasse was observed at optimal pretreatment-hydrolysis
      conditions. Significant improvement in overall ethanol yield after SSF of the
      pretreated bagasse was also observed from the best performing varieties (84.5 to
      85.6%) compared to industrial bagasse (74.5%). The ethanol concentration showed
      inverse correlation with lignin content and the ratio of xylose to arabinose, but
      it showed positive correlation with glucose yield from pretreatment-hydrolysis.
      The overall assessment of the cultivars showed greater improvement in the final
      ethanol concentration (26.9 to 33.9%) and combined ethanol yields per hectare (83
      to 94%) for the best performing varieties with respect to industrial sugarcane.
      CONCLUSIONS: These results suggest that the selection of sugarcane variety to
      optimize ethanol production from bagasse can be achieved without adversely
      affecting juice ethanol and cane yield, thus maintaining first generation ethanol
      production levels while maximizing second generation ethanol production.

PMID- 24725457
TI  - Glycoproteomic and glycomic databases.
AB  - Protein glycosylation serves critical roles in the cellular and biological
      processes of many organisms. Aberrant glycosylation has been associated with many
      illnesses such as hereditary and chronic diseases like cancer, cardiovascular
      diseases, neurological disorders, and immunological disorders. Emerging mass
      spectrometry (MS) technologies that enable the high-throughput identification of
      glycoproteins and glycans have accelerated the analysis and made possible the
      creation of dynamic and expanding databases. Although glycosylation-related
      databases have been established by many laboratories and institutions, they are
      not yet widely known in the community. Our study reviews 15 different publicly
      available databases and identifies their key elements so that users can identify
      the most applicable platform for their analytical needs. These databases include
      biological information on the experimentally identified glycans and glycopeptides
      from various cells and organisms such as human, rat, mouse, fly and zebrafish.
      The features of these databases - 7 for glycoproteomic data, 6 for glycomic data,
      and 2 for glycan binding proteins are summarized including the enrichment
      techniques that are used for glycoproteome and glycan identification. Furthermore
      databases such as Unipep, GlycoFly, GlycoFish recently established by our group
      are introduced. The unique features of each database, such as the analytical
      methods used and bioinformatical tools available are summarized. This information
      will be a valuable resource for the glycobiology community as it presents the
      analytical methods and glycosylation related databases together in one
      compendium. It will also represent a step towards the desired long term goal of
      integrating the different databases of glycosylation in order to characterize and
      categorize glycoproteins and glycans better for biomedical research. 

PMID- 24725459
TI  - Clinicopathology of graft detachment after Descemet's membrane endothelial
      keratoplasty.
AB  - PURPOSE: To investigate pathomechanisms involved in graft detachment after
      Descemet's membrane endothelial keratoplasty (DMEK) and its clinical
      implications. METHODS: In a prospective case series, 30 eyes with Fuchs'
      endothelial dystrophy underwent DMEK. Intraoperatively obtained recipients'
      endothelium-Descemet's membranes (EDMs) were investigated histologically and
      immunohistochemically. The postoperative donor graft status was categorized as
      attached or detached. Clinical and morphological parameters were analysed between
      the study groups. RESULTS: The detachment rate was 40% (12/30). There was no
      significant difference in postoperative visual acuity between the groups, but
      visual recovery was delayed in eyes with initially detached grafts. Gender, age,
      preoperative central corneal thickness or best corrected visual acuity did not
      influence the detachment rate. However, separation and disruption of the anterior
      banded layer (ABL) were frequently observed in patients with graft detachment,
      and ABL thickness was identified as a significant predictor for graft detachment.
      The ABL thickness was 2.5 +/- 0.9 MUm and 3.5 +/- 1.6 MUm in patients with
      attached and detached grafts, respectively. Immunohistologically, a deficiency of
      fibronectin and cytokeratin was observed within the ABL of patients with detached
      grafts. In contrast, a complete removal of the EDM with residual stromal collagen
      fragments was observed in patients with adherent grafts. CONCLUSIONS: Incomplete
      removal of the EDM, with residual ABL fragments on the recipients' corneal
      stroma, may be a risk factor for graft detachment after DMEK. The separation and
      disruption of the ABL might be promoted by a deficiency of matrix proteins,
      stronger biomechanical properties and a firm adherence to the posterior corneal
      stroma.

PMID- 24725460
TI  - Inflammation and infections in asthma.
AB  - INTRODUCTION: Asthma is driven by an inflammatory response against normally
      harmless environmental inorganic and organic compounds in the respiratory tract.
      Immune responses to airborne pathogens such as viruses and bacteria may reduce
      the allergic responses but are also known to trigger asthma attacks and
      eventually lead to severe disease condition. OBJECTIVE: To investigate the role
      of respiratory pathogens concerning the induction or protection against acute or
      chronic asthma manifestations. METHODS: We included 131 articles for the final
      review according to their relevance with the subject. RESULTS: There is
      apparently contradictory interaction of respiratory germs in the airways of
      asthmatics which may be protective on one angle but deleterious on the other.
      CONCLUSION: The relationship between inflammation and remodeling and the
      pathogenic role of viral and bacterial infection in the airways of asthmatic
      patients is still highly debatable and incompletely understood.

PMID- 24725461
TI  - Articular cartilage chondrocytes express aromatase and use enzymes involved in
      estrogen metabolism.
AB  - INTRODUCTION: Sex hormones, especially estrogens, have been implicated in
      articular cartilage metabolism and the pathogenesis of postmenopausal
      osteoarthritis. The conversion by aromatase (CYP19A1) of androstenedione into
      estrone (E1) and of testosterone into 17beta-estradiol (E2) plays a key role in
      the endogenous synthesis of estrogens in tissue. METHODS: We analyzed the
      expression of aromatase (CYP19A1) in immortalized C-28/I2 and T/C-28a2
      chondrocytes, as well as in cultured primary human articular chondrocytes and
      human articular cartilage tissue, by means of RT-PCR, Western blotting and
      immunohistochemistry. By means of quantitative RT-PCR and enzyme-linked
      immunosorbent assay, we also determined whether the aromatase inhibitor letrozole
      influences estrogen metabolism of cultured chondrocytes in immortalized C-28/I2
      chondrocytes. RESULTS: Aromatase mRNA was detected in both immortalized
      chondrocyte cell lines, in cultured primary human chondrocytes, and in human
      articular cartilage tissue. By means of Western blot analysis, aromatase was
      detected at the protein level in articular cartilage taken from various patients
      of both sexes and different ages. Cultured primary human articular chondrocytes,
      C-28/I2 and T/C-28a2, and human articular cartilage tissue reacted with
      antibodies for aromatase. Incubation of C-28/I2 chondrocytes with 10-11 M to 10
      7M letrozole as an aromatase inhibitor revealed significantly increased amounts
      of the mRNAs of the enzyme cytochrome P4501A1 (CYP1A1), which is involved in the
      catagen estrogen metabolism, and of the estrogen receptors ER-alpha and ER-beta.
      Concomitantly, synthesis of estrone (E1) was significantly downregulated after
      incubation with letrozole. CONCLUSIONS: We demonstrate that human articular
      cartilage expresses aromatase at the mRNA and protein levels. Blocking of estrone
      synthesis by the aromatase inhibitor letrozole is counteracted by an increase in
      ER-alpha and ER-beta. In addition, CYP1A1, an enzyme involved in catabolic
      estrogen metabolism, is upregulated. This suggests that articular chondrocytes
      use ERs functionally. The role of endogenous synthesized estrogens in articular
      cartilage health remains to be elucidated.

PMID- 24725462
TI  - Extraintestinal nematodes of the red fox Vulpes vulpes in north-west Italy.
AB  - Extraintestinal nematodes of the red fox (Vulpes vulpes) are a wide group of
      parasites that infect wild and domestic carnivores and occasionally humans.
      Nematodes in the cardiopulmonary system, stomach, urinary apparatus and muscle
      tissue of 165 red foxes (Vulpes vulpes) from north-west Italy (Liguria and
      Piedmont) were investigated between 2009 and 2012. Of the cardiopulmonary
      nematodes, a high prevalence of Angiostrongylus vasorum and Eucoleus aerophilus
      (syn. Capillaria aerophila) was found, 78.2% and 41.8% respectively; Crenosoma
      vulpis (15.8%) and Filaroides spp. (4.8%) were also found. Spirocerca lupi
      (23.5%), Aonchotheca putorii (syn. Capillaria putorii) (8.6%) and Physaloptera
      spp. (2.5%) were detected in the stomach and Pearsonema plica (syn. Capillaria
      plica) (56.8%) in the bladder. Eucoleus boehmi (syn. Capillaria boehmi) was also
      detected in the nasal cavities of one of the two foxes examined. A coprological
      examination revealed eggs of E. aerophilus, A. putorii, S. lupi, Physaloptera
      spp. and eggs of intestinal parasites. Filarial worms were absent in all the 165
      animals examined, nor was there evidence of Trichinella spp. in any of the foxes.
      The foxes were found to host a high prevalence of many species of extraintestinal
      nematodes. The prevalence of A. vasorum in foxes found in the present study is
      among the highest in Europe. In addition, to the best of our knowledge, E. boehmi
      and Filaroides spp. have never been reported before in this host in Italy. 

PMID- 24725463
TI  - Analysis of common and coding variants with cardiovascular disease in the
      Diabetes Heart Study.
AB  - BACKGROUND: Type 2 diabetes mellitus (T2DM) is a major cardiovascular disease
      (CVD) risk factor. Identification of genetic risk factors for CVD is important to
      understand disease risk. Two recent genome-wide association study (GWAS) meta
      analyses in the Cohorts for Heart and Aging Research in Genomic Epidemiology
      (CHARGE) consortium detected CVD-associated loci. METHODS: Variants identified in
      CHARGE were tested for association with CVD phenotypes, including vascular
      calcification, and conventional CVD risk factors, in the Diabetes Heart Study
      (DHS) (n = 1208; >80% T2DM affected). This included 36 genotyped or imputed
      single nucleotide polymorphisms (SNPs) from DHS GWAS data. 28 coding SNPs from 14
      top CHARGE genes were also identified from exome sequencing resources and
      genotyped, along with 209 coding variants from the Illumina HumanExome BeadChip
      genotype data in the DHS were also tested. Genetic risk scores (GRS) were
      calculated to evaluate the association of combinations of variants with CVD
      measures. RESULTS: After correction for multiple comparisons, none of the CHARGE
      SNPs were associated with vascular calcification (p < 0.0014). Multiple SNPs
      showed nominal significance with calcification, including rs599839 (PSRC1, p =
      0.008), rs646776 (CELSR2, p = 0.01), and rs17398575 (PIK3CG, p = 0.009).
      Additional COL4A2 and CXCL12 SNPs were nominally associated with all-cause or CVD
      cause mortality. Three SNPs were significantly or nominally associated with serum
      lipids: rs3135506 (Ser19Trp, APOA5) with triglycerides (TG) (p = 5*10(-5)), LDL
      (p = 0.00070), and nominally with high density lipoprotein (HDL) (p = 0.0054);
      rs651821 (5'UTR, APOA5) with increased TGs (p = 0.0008); rs13832449 (splice
      donor, APOC3) associated with decreased TGs (p = 0.0015). Rs45456595 (CDKN2A,
      Gly63Arg), rs5128 (APOC3, 3'UTR), and rs72650673 (SH2B3, Glu400Lys) were
      nominally associated with history of CVD, subclinical CVD, or CVD risk factors (p
      < 0.010). From the exome chip, rs3750103 (CHN2, His204Arg/His68Arg) with carotid
      intima-medial thickness (IMT) (p = 3.9*10(-5)), and rs61937878 (HAL, Val549Met)
      with infra-renal abdominal aorta CP (AACP) (p = 7.1*10(-5)). The unweighted GRS
      containing coronary artery calcified plaque (CAC) SNPs was nominally associated
      with history of prior CVD (p = 0.033; OR = 1.09). The weighted GRS containing
      SNPs was associated with CAC and myocardial infarction (MI) was associated with
      history of MI (p = 0.026; OR = 1.15). CONCLUSIONS: Genetic risk factors for
      subclinical CVD in the general population (CHARGE) were modestly associated with
      T2DM-related risk factors and CVD outcomes in the DHS.

PMID- 24725464
TI  - Cu(II) and dopamine bind to alpha-synuclein and cause large conformational
      changes.
AB  - alpha-Synuclein (AS) is an intrinsically disordered protein that can misfold and
      aggregate to form Lewy bodies in dopaminergic neurons, a classic hallmark of
      Parkinson's disease. The binding of Cu(II) and dopamine to AS was evaluated by
      nanopore analysis with alpha-hemolysin. In the absence of Cu(II), wild-type AS (1
      MUM) readily translocated through the pore with a blockade current of--85 pA, but
      mostly bumping events were observed in the presence of 25 MUM Cu(II). A binding
      site in the N-terminus was confirmed, because Cu(II) had no effect on the event
      profile of a peptide consisting of the C-terminal 96-140 residues. In the
      presence of dopamine (25 MUM), the translocation events at--85 pA shifted to--80
      pA, which also represents translocation events, because the event time decreases
      with increasing voltage. Events at--80 pA were also observed for the mutant A30P
      AS in the presence of dopamine. Event profiles for an N-terminal 1-60-residue
      peptide and a C-terminal 96-140-residue peptide were both altered in the presence
      of 25 MUM dopamine. In contrast, dopamine had little effect on the CD spectrum of
      AS, and a single binding site with a Ka of 3.5 * 10(3) m(-1) was estimated by
      isothermal titration calorimetry. Thus, dopamine can interact with both the N
      terminus and the C-terminus. Two-dimensional NMR spectroscopy of AS in the
      presence of dopamine showed that there were significant changes in the spectra in
      all regions of the protein. According to these findings, a model is presented in
      which dopamine induces folding between the N-terminus and C-terminus of AS.
      Partially folding conformations such as this may represent important
      intermediates in the misfolding of AS that leads to fibrillization.

PMID- 24725465
TI  - Patient-Controlled Remifentanil Analgesia as Alternative for Pethidine with
      Midazolam During Oocyte Retrieval in IVF/ICSI Procedures: A Randomized Controlled
      Trial.
AB  - BACKGROUND: Pethidine with midazolam-induced conscious sedation for pain relief
      during transvaginal oocyte retrieval for in vitro fertilization (IVF) or
      intracytoplasmic sperm injection (ICSI) procedures is associated with residual
      pain and oversedation. Patient-controlled analgesia (PCA) with remifentanil may
      serve as an alternative for pethidine. We investigated whether PCA remifentanil
      with diclofenac was associated with improved periprocedural pain relief than
      pethidine analgesia during IVF/ICSI procedures, with sedation scores, safety
      profiles, and patient satisfaction as secondary endpoints. METHODS: Seventy-six
      women were randomized to receive pethidine (2 mg/kg i.m.) and midazolam (7.5 mg)
      induced conscious sedation (n = 40) or PCA with remifentanil and diclofenac (50
      mg; n = 36). The Numeric Rating Scale, McGill Pain Questionnaire (MPQ), Ramsey
      Sedation Scale, and a 5-day pain-and-discomfort diary were used to evaluate pain
      and sedation levels. RESULTS: There were no differences in baseline
      characteristics and reproductive outcomes between both groups. Periprocedural
      pain scores were comparable for remifentanil and pethidine groups (4 [3 to 7] vs.
      6 [4 to 8]; P = 0.13). Pain scores in the pethidine group were significantly
      lower at 30 minutes after the procedure (1 [0 to 3] vs. 2 [1 to 5]; P = 0.016),
      but at cost of higher sedation levels when compared to remifentanil (4 [2 to 4]
      vs. 2 [2 to 2]; P < 0.001). Patient satisfaction was higher, and MPQ scores were
      lower in the remifentanil group. There were no differences in safety profiles
      between both analgesics. CONCLUSIONS: Patient-controlled analgesia with
      remifentanil showed a similar reduction in pain scores than pethidine with
      midazolam during oocyte retrieval, while pethidine induced the highest pain
      relief after the procedure. However, PCA remifentanil was associated with less
      sedation and a better patient satisfaction profile than pethidine.

PMID- 24725466
TI  - Should at-risk patients be paid to receive interventions?

PMID- 24725467
TI  - Atrial septal defects.
AB  - Atrial septal defects are the third most common type of congenital heart disease.
      Included in this group of malformations are several types of atrial
      communications that allow shunting of blood between the systemic and the
      pulmonary circulations. Most children with isolated atrial septal defects are
      free of symptoms, but the rates of exercise intolerance, atrial tachyarrhythmias,
      right ventricular dysfunction, and pulmonary hypertension increase with advancing
      age and life expectancy is reduced in adults with untreated defects. The risk of
      development of pulmonary vascular disease, a potentially lethal complication, is
      higher in female patients and in older adults with untreated defects. Surgical
      closure is safe and effective and when done before age 25 years is associated
      with normal life expectancy. Transcatheter closure offers a less invasive
      alternative for patients with a secundum defect who fulfil anatomical and size
      criteria. In this Seminar we review the causes, anatomy, pathophysiology,
      treatment, and outcomes of atrial septal defects in children and adult patients
      in whom this defect is the primary cardiac anomaly. 

PMID- 24725468
TI  - Use of contingency management incentives to improve completion of hepatitis B
      vaccination in people undergoing treatment for heroin dependence: a cluster
      randomised trial.
AB  - BACKGROUND: Poor adherence to treatment diminishes its individual and public
      health benefit. Financial incentives, provided on the condition of treatment
      attendance, could address this problem. Injecting drug users are a high-risk
      group for hepatitis B virus (HBV) infection and transmission, but adherence to
      vaccination programmes is poor. We aimed to assess whether contingency management
      delivered in routine clinical practice increased the completion of HBV
      vaccination in individuals receiving opioid substitution therapy. METHODS: In our
      cluster randomised controlled trial, we enrolled participants at 12 National
      Health Service drug treatment services in the UK that provided opioid
      substitution therapy and nurse-led HBV vaccination with a super-accelerated
      schedule (vaccination days 0, 7, and 21). Clusters were randomly allocated 1:1:1
      to provide vaccination without incentive (treatment as usual), with fixed value
      contingency management (three L10 vouchers), or escalating value contingency
      management (L5, L10, and L15 vouchers). Both contingency management schedules
      rewarded on-time attendance at appointments. The primary outcome was completion
      of clinically appropriate HBV vaccination within 28 days. We also did sensitivity
      analyses that examined vaccination completion with full adherence to appointment
      times and within a 3 month window. The trial is registered with Current
      Controlled Trials, number ISRCTN72794493. FINDINGS: Between March 16, 2011, and
      April 26, 2012, we enrolled 210 eligible participants. Compared with six (9%) of
      67 participants treated as usual, 35 (45%) of 78 participants in the fixed value
      contingency management group met the primary outcome measure (odds ratio 12.1,
      95% CI 3.7-39.9; p<0.0001), as did 32 (49%) of 65 participants in the escalating
      value contingency management group (14.0, 4.2-46.2; p<0.0001). These differences
      remained significant with sensitivity analyses. INTERPRETATION: Modest financial
      incentives delivered in routine clinical practice significantly improve adherence
      to, and completion of, HBV vaccination programmes in patients receiving opioid
      substitution therapy. Achievement of this improvement in routine clinical
      practice should now prompt actual implementation. Drug treatment providers should
      employ contingency management to promote adherence to vaccination programmes. The
      effectiveness of routine use of contingency management to achieve long-term
      behaviour change remains unknown. FUNDING: National Institute for Health Research
      (RP-PG-0707-10149).

PMID- 24725469
TI  - [Environmental factors and stressors that affect patient recovery in the
      Intensive Care Unit].

PMID- 24725470
TI  - Inhibitors of endopeptidase and angiotensin-converting enzyme lead to an
      amplification of the morphological changes and an upregulation of the substance P
      system in a muscle overuse model.
AB  - BACKGROUND: We have previously observed, in studies on an experimental overuse
      model, that the tachykinin system may be involved in the processes of muscle
      inflammation (myositis) and other muscle tissue alterations. To further evaluate
      the significance of tachykinins in these processes, we have used inhibitors of
      neutral endopeptidase (NEP) and angiotensin-converting enzyme (ACE), substances
      which are known to terminate the activity of various endogenously produced
      substances, including tachykinins. METHODS: Injections of inhibitors of NEP and
      ACE, as well as the tachykinin substance P (SP), were given locally outside the
      tendon of the triceps surae muscle of rabbits subjected to marked overuse of this
      muscle. A control group was given NaCl injections. Evaluations were made at 1
      week, a timepoint of overuse when only mild inflammation and limited changes in
      the muscle structure are noted in animals not treated with inhibitors. Both the
      soleus and gastrocnemius muscles were examined morphologically and with
      immunohistochemistry and enzyme immunoassay (EIA). RESULTS: A pronounced
      inflammation (myositis) and changes in the muscle fiber morphology, including
      muscle fiber necrosis, occurred in the overused muscles of animals given NEP and
      ACE inhibitors. The morphological changes were clearly more prominent than for
      animals subjected to overuse and NaCl injections (NaCl group). A marked SP-like
      expression, as well as a marked expression of the neurokinin-1 receptor (NK-1R)
      was found in the affected muscle tissue in response to injections of NEP and ACE
      inhibitors. The concentration of SP in the muscles was also higher than that for
      the NaCl group. CONCLUSIONS: The observations show that the local injections of
      NEP and ACE inhibitors led to marked SP-like and NK-1R immunoreactions, increased
      SP concentrations, and an amplification of the morphological changes in the
      tissue. The injections of the inhibitors thus led to a more marked myositis
      process and an upregulation of the SP system. Endogenously produced substances,
      out of which the tachykinins conform to one substance family, may play a role in
      mediating effects in the tissue in a muscle that is subjected to pronounced
      overuse.

PMID- 24725471
TI  - Preparation of polyhedral oligomeric silsesquioxane-based hybrid monolith by ring
      opening polymerization and post-functionalization via thiol-ene click reaction.
AB  - A polyhedral oligomeric silsesquioxane (POSS) hybrid monolith was simply prepared
      by using octaglycidyldimethylsilyl POSS (POSS-epoxy) and cystamine
      dihydrochloride as monomers via ring-opening polymerization. The effects of
      composition of prepolymerization solution and polycondensation temperature on the
      morphology and permeability of monolithic column were investigated in detail. The
      obtained POSS hybrid monolithic column showed 3D skeleton morphology and
      exhibited high column efficiency of ~71,000 plates per meter in reversed-phase
      mechanism. Owing to this POSS hybrid monolith essentially possessing a great
      number of disulfide bonds, the monolith surface would expose thiol groups after
      reduction with dithiothreitol (DTT), which supplied active sites to functionalize
      with various alkene monomers via thiol-ene click reaction. The results indicated
      that the reduction with DTT could not destroy the 3D skeleton of hybrid monolith.
      Both stearyl methylacrylate (SMA) and benzyl methacrylate (BMA) were selected to
      functionalize the hybrid monolithic columns for reversed-phase liquid
      chromatography (RPLC), while [2-(methacryloyloxy)ethyl]-dimethyl-(3-sulfopropyl)
      ammonium hydroxide (MSA) was used to modify the hybrid monolithic column in
      hydrophilic interaction chromatography (HILIC). These modified hybrid monolithic
      columns could be successfully applied for separation of small molecules with high
      efficiency. It is demonstrated that thiol-ene click reaction supplies a facile
      way to introduce various functional groups to the hybrid monolith possessing
      thiol groups. Furthermore, due to good permeability of the resulting hybrid
      monoliths, we also prepared long hybrid monolithic columns in narrow-bore
      capillaries. The highest column efficiency reached to ~70,000 plates using a 1-m
      long column of 75MUm i.d. with a peak capacity of 147 for isocratic
      chromatography, indicating potential application in separation and analysis of
      complex biosamples. 

PMID- 24725472
TI  - Stereoselective high-performance liquid chromatography and analytical method
      characterization of evacetrapib using a brush-type chiral stationary phase: a
      challenging isomeric separation requiring a unique eluent system.
AB  - Using HPLC chiral separation screening, various columns representing the
      polysaccharide, macrocyclic antibiotic and brush classes were assessed in
      multiple chromatographic modes for the separation of evacetrapib, a potential
      cardiovascular drug, from its enantiomer, two diastereomers and several
      impurities. Screening data consistently pointed to the brush-type Whelk-O 1
      chiral column as most promising for this task. A systematic separation
      optimization process is outlined using the (S,S) Whelk-O 1 chiral column, first
      for the resolution of the isomers, and later including six potential impurities.
      A relatively complex yet rugged separation system was eventually identified that
      effectively resolves all compounds within a reasonable analysis time, and should
      serve as an adequate tool for evacetrapib bulk drug enantiopurity measurement. 

PMID- 24725473
TI  - No correlation between minimal electrical charge at the tip of the stimulating
      catheter and the efficacy of the peripheral nerve block catheter for brachial
      plexus block: a prospective blinded cohort study.
AB  - BACKGROUND: Stimulating catheters offer the possibility of delivering an
      electrical charge via the tip of the catheter. This may be advantageous as it
      allows verifying if the catheter tip is in close proximity to the target nerve,
      thereby increasing catheter performance. This prospective blinded cohort study
      was designed to investigate whether there is a correlation between the minimal
      electrical charge at the tip of the stimulating catheter, and the efficacy of the
      peripheral nerve block (PNB) catheter as determined by 24 h postoperative
      morphine consumption. METHODS: Forty adult patients with ASA physical health
      classification I-III scheduled for upper extremity surgery under combined
      continuous interscalene block and general anesthesia were studied. Six patients
      were excluded from analysis.After inserting a stimulating catheter as if it were
      a non-stimulating catheter for 2-5 cm through the needle, the minimal electrical
      charge necessary to obtain an appropriate motor response was determined. A
      loading dose of 20 mL ropivacaine 0.75% ropivacaine was then administered, and
      postoperative analgesia was provided by a continuous infusion of ropivacaine 0.2%
      8 mL.h-1 via the brachial plexus catheter, and an intravenous morphine patient
      controlled analgesia (PCA) device.Main outcome measures include the minimal
      electrical charge (MEC) at the tip of the stimulating catheter necessary to
      elicit an appropriate motor response, and the efficacy of the PNB catheter as
      determined by 24 h postoperative PCA morphine consumption. RESULTS: Mean (SD)
      [range] MEC at the tip of the stimulating catheter was 589 (1414) [30 - 5000] nC.
      Mean (SD) [range] 24 h morphine consumption was 8.9 (9.9) [0-29] mg. The
      correlation between the MEC and 24 h postoperative morphine consumption was
      Spearman's Rho rs = -0.26, 95% CI -0.56 to 0.09. CONCLUSION: We conclude that
      there is no proportional relation between MEC at the tip of the blindly inserted
      stimulating catheter and 24 h postoperative morphine consumption. TRIAL
      REGISTRATION: Trialregister.nl identifier: NTR2328.

PMID- 24725474
TI  - High STAT1 mRNA levels but not its tyrosine phosphorylation are associated with
      macrophage infiltration and bad prognosis in breast cancer.
AB  - BACKGROUND: STAT1 has been attributed a function as tumor suppressor. However, in
      breast cancer data from microarray analysis indicated a predictive value of high
      mRNA expression levels of STAT1 and STAT1 target genes belonging to the
      interferon-related signature for a poor response to therapy. To clarify this
      issue we have determined STAT1 expression levels and activation by different
      methods, and investigated their association with tumor infiltration by immune
      cells. Additionally, we evaluated the interrelationship of these parameters and
      their significance for predicting disease outcome. METHODS: Expression of STAT1,
      its target genes SOCS1, IRF1, CXCL9, CXCL10, CXCL11, IFIT1, IFITM1, MX1 and genes
      characteristic for immune cell infiltration (CD68, CD163, PD-L1, PD-L2, PD-1,
      CD45, IFN-gamma, FOXP3) was determined by RT-PCR in two independent cohorts
      comprising 132 breast cancer patients. For a subset of patients, protein levels
      of total as well as serine and tyrosine-phosphorylated STAT1 were ascertained by
      immunohistochemistry or immunoblotting and protein levels of CXCL10 by ELISA.
      RESULTS: mRNA expression levels of STAT1 and STAT1 target genes, as well as
      protein levels of total and serine-phosphorylated STAT1 correlated with each
      other in neoplastic tissue. However, there was no association between tumor
      levels of STAT1 mRNA and tyrosine-phosphorylated STAT1 and between CXCL10 serum
      levels and CXCL10 expression in the tumor. Tumors with increased STAT1 mRNA
      amounts exhibited elevated expression of genes characteristic for tumor
      associated macrophages and immunosuppressive T lymphocytes. Survival analysis
      revealed an association of high STAT1 mRNA levels and bad prognosis in both
      cohorts. A similar prognostically relevant correlation with unfavorable outcome
      was evident for CXCL10, MX1, CD68, CD163, IFN-gamma, and PD-L2 expression in at
      least one collective. By contrast, activation of STAT1 as assessed by the level
      of STAT1-Y701 phosphorylation was linked to positive outcome. In multivariate Cox
      regression, the predictive power of STAT1 mRNA expression was lost when including
      expression of CXCL10, MX1 and CD68 as confounders. CONCLUSIONS: Our study
      confirms distinct prognostic relevance of STAT1 expression levels and STAT1
      tyrosine phosphorylation in breast cancer patients and identifies an association
      of high STAT1 levels with elevated expression of STAT1 target genes and markers
      for infiltrating immune cells.

PMID- 24725475
TI  - A double-blind, randomized, multicenter, controlled trial of suspended
      polymethylmethacrylate microspheres for the correction of atrophic facial acne
      scars.
AB  - BACKGROUND: Acne scarring remains a stubborn clinical problem. Few treatments
      have been shown to be definitely effective for this problem.
      Polymethylmethacrylate (PMMA) microspheres in collagen (ArteFill, Suneva Medical
      Inc, Santa Barbara, CA) have shown long-term benefit for nasolabial fold
      treatment. A pilot study has shown benefit for PMMA-collagen in atrophic acne
      scarring. OBJECTIVE: We sought to demonstrate the safety and effectiveness of
      PMMA-collagen for acne scarring in a controlled, blinded trial. METHODS: Subjects
      with at least 4 moderate to severe rolling, atrophic scars randomly received PMMA
      collagen or saline injections. Subjects underwent up to 2 injection sessions and
      were followed up for 6 months. Efficacy was assessed using a validated rating
      scale for each scar. RESULTS: In all, 147 subjects underwent injections. Success
      was achieved by 64% of those treated with PMMA-collagen compared with 33% of
      control subjects (P = .0005). The treatment showed excellent safety with
      generally mild, reversible adverse events. No significant differences in efficacy
      or safety were noted between genders, for darker skin types, or in older age
      groups. LIMITATIONS: Subjects were followed up for only 6 months. CONCLUSION:
      PMMA-collagen demonstrates substantial effectiveness in the treatment of atrophic
      acne scars of the face while maintaining an excellent safety profile. Further
      follow-up should be undertaken to demonstrate longer-term benefit and safety.

PMID- 24725476
TI  - A retrospective analysis of the duration of oral antibiotic therapy for the
      treatment of acne among adolescents: investigating practice gaps and potential
      cost-savings.
AB  - BACKGROUND: Duration of oral antibiotic therapy in acne has not been widely
      studied. Recent guidelines suggest it should be limited to 3 to 6 months.
      OBJECTIVE: We sought to compare the duration of oral antibiotic use with recent
      guidelines and determine the potential cost-savings related to shortened
      durations. METHODS: This is a retrospective cohort study from the MarketScan
      Commercial Claims and Encounters database. Claims data were used to determine
      duration and costs of antibiotic therapy. RESULTS: The mean course duration was
      129 days. The majority (93%) of courses were less than 9 months. Among the 31,634
      courses, 18,280 (57.8%) did not include concomitant topical retinoid therapy. The
      mean (95% confidence interval) duration with and without topical retinoid use was
      133 (131.5-134.7) days and 127 (125.4-127.9) days, respectively. The mean excess
      direct cost of antibiotic treatment for longer than 6 months was $580.99/person.
      LIMITATIONS: Claims cannot be attributed to a specific diagnosis or provider. The
      database does not provide information on acne severity. CONCLUSIONS: Duration of
      antibiotic use is decreasing when compared with previous data. However, 5547
      (17.53%) courses exceeded 6 months, highlighting an opportunity for reduced
      antibiotic use. If courses greater than 6 months were shortened to 6 months,
      savings would be $580.99/person.

PMID- 24725478
TI  - In vivo reflectance confocal microscopy to monitor the response of lentigo
      maligna to imiquimod.
AB  - BACKGROUND: Imiquimod has been used for treating lentigo maligna (LM) in selected
      cases when surgery is not an appropriate option because of functional or
      aesthetic impairment. Reflectance confocal microscopy (RCM) is a noninvasive
      method that has not been validated for monitoring the treatment of LM with
      imiquimod. OBJECTIVE: We sought to evaluate the use of in vivo RCM to accurately
      monitor the response of LM to nonsurgical treatment with topical imiquimod.
      METHODS: Twenty patients with confirmed facial LM, not amenable to surgical
      treatment or radiation therapy, were included prospectively. Clinical evaluation
      was performed by dermoscopy, RCM, and histopathology. Patients applied imiquimod
      5% for 8 weeks. The affected area was assessed using the previously described LM
      score on RCM, and target sample biopsies were performed to confirm or discard RCM
      findings. RESULTS: Fifteen of the 20 patients (75%) presented histologic tumor
      clearance. Confocal microscopy identified 70% of these responders with no false
      negative results, and when compared with histopathology, there was no significant
      difference in evaluating the response to imiquimod. LIMITATIONS: The
      impossibility of examining the entire lesion by means of histopathology is a
      limitation. CONCLUSION: In vivo RCM evaluation was useful in accurately
      monitoring the response of LM to nonsurgical treatment with topical imiquimod in
      patients when surgery is contraindicated.

PMID- 24725477
TI  - Skin cancer in organ transplant recipients: more than the immune system.
AB  - Organ transplant recipients (OTRs) are at increased risk of developing
      nonmelanoma skin cancers. This has long been thought to be caused by
      immunosuppression and viral infection. However, skin cancer risk among
      individuals with AIDS or iatrogenic immunodeficiency does not approach the levels
      seen in OTRs, suggesting other factors play a critical role in oncogenesis. In
      clinical trials of OTRs, switching from calcineurin inhibitors to mammalian
      target of rapamycin inhibitors consistently led to a significant reduction in the
      risk of developing new skin cancers. New evidence suggests calcineurin inhibitors
      interfere with p53 signaling and nucleotide excision repair. These two pathways
      are associated with nonmelanoma skin cancer, and squamous cell carcinoma in
      particular. This finding may help explain the predominance of squamous cell
      carcinoma over basal cell carcinoma in this population. Mammalian target of
      rapamycin inhibitors do not appear to impact these pathways. Immunosuppression,
      viral infection, and impaired DNA repair and p53 signaling all interact in OTRs
      to create a phenotype of extreme risk for nonmelanoma skin cancer. 

PMID- 24725479
TI  - Predictors of early literacy skills in children with intellectual disabilities: a
      clinical perspective.
AB  - The present study investigated the linguistic and cognitive predictors of early
      literacy in 17 children with intellectual disabilities (ID) (mean age: 7; 6
      years) compared to 24 children with normal language acquisition (NLA) (mean age:
      6; 0 years), who were all in the so-called partial alphabetic phase of reading
      (Ehri, 2005). In each group, children's performances in early literacy skills
      (phonological awareness, letter knowledge, and word decoding) were assessed, as
      well as their achievement in linguistic and cognitive measures associated to
      these skills. The results showed that, notwithstanding the fact that there were
      no differences in word decoding, children with ID lagged behind on all predictor
      measures relevant to early literacy skills compared to children with NLA.
      Moreover, whereas children with NLA showed a regular predictive pathway of early
      literacy skills, children with ID showed a deviant pattern, in which nonverbal
      intelligence and rhythmic skills proved to be of major importance. Also letter
      knowledge appeared to be involved in their early literacy processing. It can be
      tentatively concluded that in the ID group, children's level of nonverbal
      intellectual abilities in combination with rhythmic ability proves pivotal in the
      development of their early literacy skills. 

PMID- 24725480
TI  - Theranostic applications of antibodies in oncology.
AB  - Targeted therapies, including antibodies, are becoming increasingly important in
      cancer therapy. Important limitations, however, are that not every patient
      benefits from a specific antibody therapy and that responses could be short-lived
      due to acquired resistance. In addition, targeted therapies are quite expensive
      and are not completely devoid of side-effects. This urges the need for accurate
      patient selection and response monitoring. An important step towards
      personalizing antibody treatment could be the implementation of theranostics.
      Antibody theranostics combine the diagnostic and therapeutic potential of an
      antibody, thereby selecting those patients who are most likely to benefit from
      antibody treatment. This review focuses on the clinical application of
      theranostic antibodies in oncology. It provides detailed information concerning
      the suitability of antibodies for theranostics, the different types of
      theranostic tests available and summarizes the efficacy of theranostic antibodies
      used in current clinical practice. Advanced theranostic applications, including
      radiolabeled antibodies for non-invasive functional imagining, are also
      addressed. Finally, we discuss the importance of theranostics in the emerging
      field of personalized medicine and critically evaluate recent data to determine
      the best way to apply antibody theranostics in the future. 

PMID- 24725482
TI  - Exploring bacterial epigenomics in the next-generation sequencing era: a new
      approach for an emerging frontier.
AB  - Epigenetics has an important role for the success of foodborne pathogen
      persistence in diverse host niches. Substantial challenges exist in determining
      DNA methylation to situation-specific phenotypic traits. DNA modification,
      mediated by restriction-modification systems, functions as an immune response
      against antagonistic external DNA, and bacteriophage-acquired methyltransferases
      (MTase) and orphan MTases - those lacking the cognate restriction endonuclease -
      facilitate evolution of new phenotypes via gene expression modulation via DNA and
      RNA modifications, including methylation and phosphorothioation. Recent
      establishment of large-scale genome sequencing projects will result in a
      significant increase in genome availability that will lead to new demands for
      data analysis including new predictive bioinformatics approaches that can be
      verified with traditional scientific rigor. Sequencing technologies that detect
      modification coupled with mass spectrometry to discover new adducts is a powerful
      tactic to study bacterial epigenetics, which is poised to make novel and far
      reaching discoveries that link biological significance and the bacterial
      epigenome. 

PMID- 24725483
TI  - Bibliometric analysis of scientific publications on waterpipe (narghile, shisha,
      hookah) tobacco smoking during the period 2003-2012.
AB  - BACKGROUND: Waterpipe tobacco smoking has spread worldwide. However, the
      evaluation of scientific output in the field of waterpipe tobacco smoking has not
      been studied yet. The main objectives of this study were to analyze worldwide
      research output in the waterpipe tobacco smoking field, and to examine the
      authorship pattern and the citations retrieved from the Scopus database for over
      a decade. METHODS: Data from January 1, 2003 through December 31, 2012 were
      searched for documents with specific words regarding waterpipe tobacco smoking as
      "keywords" in the title. Scientific output was evaluated based on a methodology
      developed and used in other bibliometric studies: (a) total and trends of
      contributions in waterpipe tobacco smoking research between 2003 and 2012; (b)
      authorship patterns and research productivity; (c) collaboration patterns; (d)
      the citations received by the publications; and (e) areas of interest of the
      published papers. RESULTS: Worldwide there were 334 publications that met the
      criteria during the study period. The largest number of publications in waterpipe
      tobacco smoking were from the United States of America (USA) (33.5%), followed by
      Lebanon (15.3%), and France (10.5%). The total number of citations at the time of
      data analysis (October 18, 2013) was 4,352, with an average of 13 citations per
      document and a median (interquartile range) of 4.0 (1.0-16.0). The h-index of the
      retrieved documents was 34. The highest h-index by country was 27 for the USA,
      followed by 20 for Syrian Arab Republic and Lebanon. CONCLUSIONS: The present
      data reveal a promising rise and a good start for research activity in the field
      of waterpipe tobacco smoking. More effort is needed to bridge the gap in
      waterpipe smoking-based research and to promote better evaluation of waterpipe
      smoking, risks, health effects, or control services worldwide.

PMID- 24725481
TI  - Garbage in, garbage out: a critical evaluation of strategies used for validation
      of immunohistochemical biomarkers.
AB  - The use of immunohistochemistry (IHC) in clinical cohorts is of paramount
      importance in determining the utility of a biomarker in clinical practice. A
      major bottleneck in translating a biomarker from bench-to-bedside is the lack of
      well characterized, specific antibodies suitable for IHC. Despite the widespread
      use of IHC as a biomarker validation tool, no universally accepted
      standardization guidelines have been developed to determine the applicability of
      particular antibodies for IHC prior to its use. In this review, we discuss the
      technical challenges faced by the use of immunohistochemical biomarkers and
      rigorously explore classical and emerging antibody validation technologies. Based
      on our review of these technologies, we provide strict criteria for the pragmatic
      validation of antibodies for use in immunohistochemical assays. 

PMID- 24725484
TI  - What do the screening trials really tell us and where do we go from here?
AB  - Publication of apparently conflicting results from 2 large trials of prostate
      cancer screening has intensified the debate about prostate-specific antigen (PSA)
      testing and has led to a recommendation against screening from the US Preventive
      Services Task Force. This article reviews the trials and discusses the
      limitations of their empirical results in informing public health policy. In
      particular, the authors explain why harm-benefit trade-offs based on empirical
      results may not accurately reflect the trade-offs expected under long-term
      population screening. This information should be useful to clinicians in
      understanding the implications of these studies regarding the value of PSA
      screening. 

PMID- 24725485
TI  - Evolution and immediate future of US screening guidelines.
AB  - Although observational studies and simulation models have shed some interesting
      light on many of the uncertainties surrounding prostate cancer screening, well
      done clinical trials provide the best evidence on screening among the extremes of
      age, the most appropriate interval to screen, and the best complement of tests to
      use. Enthusiasm for screening is temporized by the acknowledgment that
      overdetection leads to frequent overtreatment despite evidence supporting the
      safety of active surveillance in many men with low-risk disease. 

PMID- 24725486
TI  - International perspectives on screening.
AB  - The estimated population of the world in 2008 was 6.75 billion people, increasing
      by around 79 million people each year. The world population is aging. In 1970,
      the world median age was 22 years; it is projected to reach 38 years by 2050. The
      number of people in the world aged 60 years and older is expected to almost
      triple to 2 billion by 2050. Because cancer, especially prostate cancer, is
      predominantly a disease of the elderly, increases in the number of older people
      will lead to more cases of cancer, even if current incidence rates remain the
      same.

PMID- 24725487
TI  - The politics of prostate cancer screening.
AB  - The controversial recent recommendation by the United States Preventive Services
      Task Force (USPSTF) against prostate-specific antigen (PSA) screening for early
      stage prostate cancer has caused much debate. Whereas USPSTF recommendations
      against routine screening mammography in younger women resulted in fierce public
      outcry and eventual alteration in the language of the recommendation, the same
      public and political response has not been seen with PSA screening for prostate
      cancer. It is of paramount importance to ensure improved efficiency and
      transparency of the USPSTF recommendation process, and resolution of concerns
      with the current USPSTF recommendation against PSA screening for all ages. 

PMID- 24725488
TI  - Decision making and prostate cancer screening.
AB  - This article presents an overview of the challenges that men encounter in making
      decisions about prostate cancer screening, including complex affective and
      cognitive factors and controversies in the interpretation of the evidence on
      prostate cancer screening. Shared decision making involving patient decision aids
      are discussed as approaches that can be used to improve the quality of prostate
      cancer screening decisions, including a close alignment between a man's values,
      goals, and preferences and his choice about screening. 

PMID- 24725490
TI  - The epidemiology and clinical implications of genetic variation in prostate
      cancer.
AB  - There is strong evidence of a genetic predisposition to prostate cancer. Recent
      advances in genetic sequencing technologies have permitted significant advances
      in the field. This article reviews the genetic basis underlying prostate cancer,
      and highlights the epidemiology and potential clinical usefulness of both rare
      and common genetic variations. In addition, recent findings related to the
      understanding of prostate cancer genetics are discussed. 

PMID- 24725489
TI  - Emerging PSA-based tests to improve screening.
AB  - This article updates advances in prostate cancer screening based on prostate
      specific antigen, its derivatives, and human kallikrein markers. Many men are
      diagnosed with indolent disease not requiring treatment. Although there is
      evidence of a survival benefit from screening, the numbers needed to screen and
      treat remain high. There is risk of exposing men to the side effects of treatment
      for nonthreatening disease. A screening test is needed with sufficiently good
      performance characteristics to detect disease at an early stage so treatment may
      be offered with curative intent, while reducing the number of negative or
      unnecessary biopsies. 

PMID- 24725492
TI  - Screening and detection advances in magnetic resonance image-guided prostate
      biopsy.
AB  - Multiparametric magnetic resonance imaging (MRI) has provided a method for
      visualizing prostate cancer. MRI-ultrasonography fusion allows prostate biopsy to
      be performed quickly, on an outpatient basis, using the transrectal technique.
      Targeted biopsies are more sensitive for detection of prostate cancer than
      nontargeted, systematic biopsies and detect more significant prostate cancers and
      fewer insignificant cancers than conventional biopsies. A negative MRI scan
      should not defer biopsy. Two groups who will especially benefit from targeted
      prostate biopsy are men with low-risk lesions in active surveillance and men with
      increased prostate-specific antigen levels and previous negative conventional
      biopsies. 

PMID- 24725493
TI  - Management of an increasing prostate-specific antigen level after negative
      prostate biopsy.
AB  - Patients who have a previously negative biopsy in the setting of clinical
      suspicion of prostate cancer still have a high risk of harboring significant
      undiagnosed disease. Various markers such as prostate-specific antigen (PSA)
      velocity, PSA density, PCA3, and newer markers may aid in repeat biopsy
      selection. Repeating the same biopsy procedure in such patients does not yield
      high cancer detection rates. More anteriorly directed transrectal or
      transperineal biopsies are indicated. Multiparametric magnetic resonance imaging
      can detect abnormal areas, and lesion-targeted biopsies can improve the cancer
      detection rate. 

PMID- 24725494
TI  - When is prostate cancer really cancer?
AB  - Several investigators have challenged the idea that low-grade cancers are a cause
      for concern, suggesting that the term cancer should not be applied to these
      tumors. This article reviews the defining features of cancer, and the diagnostic
      and prognostic classification systems currently used for prostate cancer.
      Logical, morphologic, and molecular evidence is presented to show that low-grade
      prostate cancers are correctly classified as cancer. The authors suggest,
      however, that 6 out of 10 on an aggressiveness scale is inappropriate for
      indolent cancer, and that a proposed reinterpretation of Gleason grading
      categories is a more logical way to address overtreatment. 

PMID- 24725491
TI  - Optimization of prostate biopsy: review of technique and complications.
AB  - A 12-core systematic biopsy that incorporates apical and far-lateral cores in the
      template distribution allows maximal cancer detection and avoidance of a repeat
      biopsy while minimizing the detection of insignificant prostate cancers. Magnetic
      resonance imaging-guided prostate biopsy has an evolving role in both initial and
      repeat prostate biopsy strategies, potentially improving sampling efficiency,
      increasing the detection of clinically significant cancers, and reducing the
      detection of insignificant cancers. Hematuria, hematospermia, and rectal bleeding
      are common complications of prostate needle biopsy, but are generally self
      limiting and well tolerated. All men should receive antimicrobial prophylaxis
      before biopsy. 

PMID- 24725495
TI  - Early detection of prostate cancer.

PMID- 24725496
TI  - Early detection of prostate cancer.

PMID- 24725497
TI  - A new pattern of pulmonary graft vs host disease in a hematopoietic stem cell
      transplant patient.
AB  - BACKGROUND: The primary pulmonary manifestation of chronic graft vs host disease
      (GvHD) is the development of bronchiolitis obliterans. Other pulmonary
      manifestations of chronic GvHD that have been reported include diffuse alveolar
      damage, lymphocytic interstitial pneumonia, bronchiolitis organising pneumonia
      and lymphocytic bronchiolitis/bronchitis. CASE PRESENTATION: We report an unusual
      case of a 34-year-old patient with acute myeloid leukaemia, status post-allogenic
      hematopoietic stem cell transplantation who subsequently developed GvHD with skin
      involvement. He presented to our hospital with new onset respiratory failure and
      on subsequent surgical lung biopsy was found to have non-specific interstitial
      pneumonia (NSIP). CONCLUSION: This is the third case of a patient with biopsy
      proven GvHD who had NSIP pattern on surgical lung biopsy. We believe this may
      represent a rare manifestation of pulmonary GvHD.

PMID- 24725498
TI  - Translation and validation of the Turkish language version of the Rheumatoid
      Arthritis Disease Activity Index-5.
AB  - AIM: The purpose of this study was to translate the Rheumatoid Arthritis Disease
      Activity Index-5 (RADAI-5), which is a tool for measuring disease activity in
      rheumatoid arthritis (RA) patients, into Turkish language and prove its validity,
      reliability and sensitivity to changes. METHODS: Translation from the original
      German version was performed according to the standardized methods. One hundred
      and two patients with RA completed in the Turkish RADAI-5 twice within 3 days
      interval. Internal consistency and test-retest reliability was investigated by
      calculating Cronbach's alpha and intra-class correlation coefficients (ICC),
      respectively. Validity was assessed by analyzing the correlations between the
      Turkish RADAI-5 and some measurement tools evaluating the disease activity,
      functional status and quality of life. To test the scale's responsiveness to the
      changes, another 23 patients with uncontrolled disease activity and three newly
      diagnosed RA patients completed the RADAI-5 before and after a biologic agent or
      methotrexate treatment. RESULTS: There were no floor or ceiling effects.
      Cronbach's alpha (0.91) and ICC (0.997) values certified the Turkish version's
      reliability. Strong correlations between the Turkish questionnaire and Disease
      Activity Score-28 (DAS28), DAS28-CRP, DAS28-three variables, Health Assessment
      Questionnaire, Rheumatoid Arthritis Quality of Life questionnaire, patient's and
      doctor's global assessments, tender joint count proved the convergent validity of
      the scale. Effect size (3.08) demonstrated that the Turkish RADAI-5 is sensitive
      to the changes. CONCLUSION: The Turkish RADAI-5 is a feasible, reliable and valid
      questionnaire and sensitive to changes; thus it can be used to monitor disease
      activity in Turkish RA patients.

PMID- 24725499
TI  - Norms for performance in the workplace in healthy people: data from the national
      comorbidity survey replication study.
AB  - IntroductionPsychiatric conditions affect multiple areas of psychosocial
      functioning, including functioning in the workplace. The purpose of this study
      was to establish norms for absenteeism (work days missed due to mental or
      physical illness) and work performance (quality of work performed when at work)
      for healthy individuals. METHODS: We selected 300 individuals without psychiatric
      or medical conditions from the National Comorbidity Survey Replication study (NCS
      R). Absenteeism and work performance were assessed using the NCS-R version of the
      Health and Work Performance Questionnaire (HPQ). RESULTS: Employees missed an
      average of 5.1 days of work in the past year. Absenteeism varied across
      occupations, with performers of routine tasks, office clerks, and professionals
      exhibiting the greatest variance in days missed. Work performance ratings were
      skewed toward high performance ratings and did not differ across occupations.
      Gender, age, race/ethnicity, and education level did not substantially moderate
      absenteeism and work performance norms.DiscussionSkewed ratings for work
      performance are consistent with previous findings using the HPQ. This may reflect
      a general tendency that individuals rate themselves favorably when they compare
      themselves to others. CONCLUSION: This study provides normative tables for
      absenteeism and work performance in individuals without psychiatric or medical
      conditions, against which individuals with such conditions may be compared.

PMID- 24725500
TI  - Obsessive musical hallucinations in a schizophrenia patient: psychopathological
      and FMRI characteristics.
AB  - Obsessive-compulsive symptoms (OCS) are relatively common and clinically
      significant phenomena in schizophrenia patients, suggesting the existence of a
      separate schizo-obsessive subgroup of the disorder. Although a majority of schizo
      obsessive patients have typical ego-dystonic OCS, a meaningful proportion
      exhibits diagnostically challenging psychopathological phenomena, psychotic in
      content and obsessive in form. We report the clinical and functional magnetic
      resonance imaging characteristics of a schizophrenia patient who developed
      auditory hallucinations with musical content and obsessive in form. We suggest
      that "obsessive musical hallucinations", that integrate both psychotic and
      obsessive-compulsive disorder (OCD)-related features, may be mediated by the
      brain networks believed to be involved in OCD and in auditory musical
      hallucinations. 

PMID- 24725501
TI  - Cytokines in bipolar disorder: recent findings, deleterious effects but promise
      for future therapeutics.
AB  - An emerging body of evidence points to impairments in neuroplasticity, cell
      resilience, and neuronal survival as major pathophysiological mechanisms in
      bipolar disorder. Neuronal survival is influenced by several factors including an
      orchestrated action of neurotransmitters, hormones, and neurotrophins. Patients
      with bipolar disorder exhibit increased peripheral level of inflammatory
      mediators such as cytokines, mainly during acute mood episodes. These mediators
      interact in several pathways involved in regulation of mood and energy including
      hypothalamic-pituitary-adrenal axis and monoamine metabolism. Importantly,
      inflammatory cytokines have a potential role in controlling neuronal and glial
      cell loss that occurs during mood episodes, especially during mania, as they are
      the most powerful extracellular stimuli to apoptosis. Bipolar patients have been
      reported to show imbalanced peripheral production of cytokines both at the mRNA
      and protein levels, associated signal transduction machinery, as well as to have
      specific functional polymorphisms in the genes that encode these cytokines.
      Interestingly, lithium, valproate, and several antidepressants have demonstrated
      to have immunomodulatory properties. Growing evidence supports the involvement of
      inflammatory mechanisms in bipolar disorder, opening new paths of investigation
      using immunomodulatory medications. These findings can offer not only an
      opportunity of treating mood symptoms but also understanding and reverting
      neurobiological changes associated with the disorder. 

PMID- 24725502
TI  - Advanced glycation endproducts trigger autophagy in cadiomyocyte via
      RAGE/PI3K/AKT/mTOR pathway.
AB  - Previous studies showed that the accumulation of advanced glycation end products
      (AGEs) induce cardiomyocyte apoptoisis, leading to heart dysfunction. However,
      the effect of AGEs on another cell death pathway, autophagy, in cardiomyocytes
      remains unknown. METHODS: Rat neonate cardiomyocytes were cultured and treated
      with AGEs at different concentration. Two classic autophagy markers, microtubule
      associated protein 1 light chain 3 (LC3) and Beclin-1, were detected by western
      blot assay. The inhibition of RAGE and phosphatidylinositol 3-phosphate kinase
      (PI3K)/Akt/mTOR pathway were applied to cells, respectively. RESULTS: AGEs
      administration enhanced the expression of Beclin-1 and LC3 II in cardiomyocytes,
      increased the number of autophagic vacuoles and impaired the cell viability in
      dose-dependant manners. Also, AGEs inhibited the PI3K/Akt/mTOR pathway via RAGE.
      Inhibition of RAGE with RAGE antibody reduced expression of Beclin-1 and LC3 II/I
      and inhibited the cellular autophagy, accompanied by the reactivation of
      PI3K/Akt/mTOR pathway in cultured cells. Notably, the presence of inhibition of
      PI3K/Akt/mTOR pathway abolished the protective effect of RAGE inhibition on
      cardiomyocytes. CONCLUSION: This study provides evidence that AGEs induces
      cardiomyocyte autophagy by, at least in part, inhibiting the PI3K/Akt/mTOR
      pathway via RAGE.

PMID- 24725503
TI  - Behavioural changes and muscle strength in Rattus norvegicus experimentally
      infected with Toxocara cati and T. canis.
AB  - Toxocara canis and Toxocara cati are nematode parasites in dogs and cats,
      respectively, transmitted by ingestion of embryonated eggs, transmammary and
      transplacental (T. canis) routes and paratenic host predation. Many parasites use
      mechanisms that change the behaviour of their hosts to ensure continued
      transmission. Several researchers have demonstrated behavioural changes in mouse
      models as paratenic hosts for T. canis. However, there have been no studies on
      behavioural changes in laboratory rats (Rattus norvegicus) experimentally
      infected with T. cati. This study investigated behavioural changes and muscle
      strength in male and female rats experimentally infected with T. cati or T. canis
      in acute and chronic phases of infection. Regardless of sex, rats infected with
      T. cati showed a greater decrease in muscle strength 42 days post infection
      compared to rats infected with T. canis. However, behavioural changes were only
      observed in female rats infected with T. canis. 

PMID- 24725504
TI  - Land usage attributed to corn ethanol production in the United States:
      sensitivity to technological advances in corn grain yield, ethanol conversion,
      and co-product utilization.
AB  - BACKGROUND: Although the system for producing yellow corn grain is well
      established in the US, its role among other biofeedstock alternatives to
      petroleum-based energy sources has to be balanced with its predominant purpose
      for food and feed as well as economics, land use, and environmental stewardship.
      We model land usage attributed to corn ethanol production in the US to evaluate
      the effects of anticipated technological change in corn grain production, ethanol
      processing, and livestock feeding through a multi-disciplinary approach. Seven
      scenarios are evaluated: four considering the impact of technological advances on
      corn grain production, two focused on improved efficiencies in ethanol
      processing, and one reflecting greater use of ethanol co-products (that is,
      distillers dried grains with solubles) in diets for dairy cattle, pigs, and
      poultry. For each scenario, land area attributed to corn ethanol production is
      estimated for three time horizons: 2011 (current), the time period at which the
      15 billion gallon cap for corn ethanol as per the Renewable Fuel Standard is
      achieved, and 2026 (15 years out). RESULTS: Although 40.5% of corn grain was
      channeled to ethanol processing in 2011, only 25% of US corn acreage was
      attributable to ethanol when accounting for feed co-product utilization. By 2026,
      land area attributed to corn ethanol production is reduced to 11% to 19%
      depending on the corn grain yield level associated with the four corn production
      scenarios, considering oil replacement associated with the soybean meal
      substituted in livestock diets with distillers dried grains with solubles.
      Efficiencies in ethanol processing, although producing more ethanol per bushel of
      processed corn, result in less co-products and therefore less offset of corn
      acreage. Shifting the use of distillers dried grains with solubles in feed to
      dairy cattle, pigs, and poultry substantially reduces land area attributed to
      corn ethanol production. However, because distillers dried grains with solubles
      substitutes at a higher rate for soybean meal, oil replacement requirements
      intensify and positively feedback to elevate estimates of land usage.
      CONCLUSIONS: Accounting for anticipated technological changes in the corn ethanol
      system is important for understanding the associated land base ascribed, and may
      aid in calibrating parameters for land use models in biofuel life-cycle analyses.

PMID- 24725505
TI  - Magnetite compensates for the lack of a pilin-associated c-type cytochrome in
      extracellular electron exchange.
AB  - Nanoscale magnetite can facilitate microbial extracellular electron transfer that
      plays an important role in biogeochemical cycles, bioremediation and several
      bioenergy strategies, but the mechanisms for the stimulation of extracellular
      electron transfer are poorly understood. Further investigation revealed that
      magnetite attached to the electrically conductive pili of Geobacter species in a
      manner reminiscent of the association of the multi-heme c-type cytochrome OmcS
      with the pili of Geobacter sulfurreducens. Magnetite conferred extracellular
      electron capabilities on an OmcS-deficient strain unable to participate in
      interspecies electron transfer or Fe(III) oxide reduction. In the presence of
      magnetite wild-type cells repressed expression of the OmcS gene, suggesting that
      cells might need to produce less OmcS when magnetite was available. The finding
      that magnetite can compensate for the lack of the electron transfer functions of
      a multi-heme c-type cytochrome has implications not only for the function of
      modern microbes, but also for the early evolution of microbial electron transport
      mechanisms. 

PMID- 24725506
TI  - Tetramethylpyrazine inhibits angiotensin II-induced activation of hepatic
      stellate cells associated with interference of platelet-derived growth factor
      beta receptor pathways.
AB  - Liver fibrosis represents a frequent event following chronic insult to trigger
      wound healing responses in the liver. Activation of hepatic stellate cells (HSCs)
      is a pivotal event during liver fibrogenesis. Compelling evidence indicates that
      the renin-angiotensin system (RAS) takes part in the pathogenesis of liver
      fibrosis. Angiotensin II (Ang II), the primary effector peptide of the RAS, has
      been demonstrated to be a potent pro-fibrogenic molecule for HSC activation. In
      this study we investigated the effects of tetramethylpyrazine (TMP) on HSC
      activation induced by Ang II in order to elucidate the underlying mechanisms. Our
      results demonstrated that Ang II significantly promoted cell growth, upregulated
      the expression of the fibrotic markers alpha-smooth muscle actin (alpha-SMA) and
      alpha1(I) procollagen, and enhanced the invasion capacity in HSCs. TMP inhibited
      proliferation and arrested the cell cycle at the G2/M checkpoint associated with
      altering several cell cycle regulatory proteins in Ang II-treated HSCs. TMP also
      modulated Bcl-2 family proteins and activated the caspase cascade leading to
      apoptosis in Ang II-treated HSCs. Moreover, TMP reduced the expression of alpha
      SMA and alpha1(I) procollagen at mRNA and protein levels, and these effects were
      associated with interference of the platelet-derived growth factor beta receptor
      (PDGF-betaR) mediated PI3K/AKT/mTOR pathway in HSCs exposed to Ang II.
      Furthermore, Ang II-enhanced HSC invasion capacity was diminished by TMP, which
      was associated with interference of PDGF-betaR/FAK signaling. These data
      collectively indicated that interference of PDGF-betaR-mediated fibrotic pathways
      was involved in TMP inhibition of HSC activation caused by Ang II, providing
      novel mechanistic insights into TMP as a potential therapeutic remedy for hepatic
      fibrosis. 

PMID- 24725507
TI  - Face recognition in patients with migraine.
AB  - OBJECTIVES: Prosopagnosia is a rare dysfunction seen during the aura phase of
      migraine. We aimed to evaluate the face recognition, which has not previously
      been investigated in migraineurs during the interictal period, and its
      relationships with clinical features. METHODS: Seventy-four migraineurs, with or
      without aura, diagnosed according to the International Headache Society criteria
      and 37 healthy control subjects were included. Benton face recognition test
      (BFRT) and judgment of line orientation test (LOT) for complex visual perception
      were applied to all participants. RESULTS: Migraineurs showed significantly lower
      performance in both of the BFRT and LOT scores (P = 0.027; P = 0.014,
      respectively), indicating impaired visuospatial perception. In the subgroup
      analysis, these impairments were more pronounced in the group with migraine
      without aura. CONCLUSION: Migraineurs had poorer performance in both face
      recognition and visuospatial perception. These findings could be based on
      functional differences in the migraineurs' brain or genetic changes.

PMID- 24725508
TI  - Impacts of anthropogenic disturbances at deep-sea hydrothermal vent ecosystems: a
      review.
AB  - Deep-sea hydrothermal-vent ecosystems have stimulated decades of scientific
      research and hold promise of mineral and genetic resources that also serve
      societal needs. Some endemic taxa thrive only in vent environments, and vent
      associated organisms are adapted to a variety of natural disturbances, from tidal
      variations to earthquakes and volcanic eruptions. In this paper, physicochemical
      and biological impacts of a range of human activities at vents are considered.
      Mining is currently the only anthropogenic activity projected to have a major
      impact on vent ecosystems, albeit at a local scale, based on our current
      understanding of ecological responses to disturbance. Natural recovery from a
      single mining event depends on immigration and larval recruitment and
      colonization; understanding processes and dynamics influencing life-history
      stages may be a key to effective minimization and mitigation of mining impacts.
      Cumulative impacts on benthic communities of several mining projects in a single
      region, without proper management, include possible species extinctions and
      shifts in community structure and function.

PMID- 24725509
TI  - Farming-up coastal fish assemblages through a massive aquaculture escape event.
AB  - We investigated the changes on the mean trophic level of fish assemblages across
      different spatiotemporal scales, before and after a massive escape event occurred
      off La Palma (Canary Islands), which resulted in the release of 1.5 million fish
      (mostly Dicentrarchus labrax) into the wild. The presence of escaped fish altered
      significantly the mean trophic level of fish assemblages in shallow coastal
      waters. This alteration was exacerbated by the massive escape. A nearby marine
      protected area buffered the changes in mean trophic level but exhibited the same
      temporal patterns as highly fished areas. Moreover, escaped fish exploited
      natural resources according to their total length and possibly, time since
      escapement. New concerns arise as a "farming up" process is detected in shallow
      coastal fish assemblages where marine aquaculture is established. 

PMID- 24725510
TI  - Dental pathology of the California sea lion (Zalophus californianus).
AB  - Skulls from 1,085 California sea lions (Zalophus californianus) were examined
      macroscopically according to defined criteria. The museum specimens, 61.8% male
      and 37.3% female, were acquired from strandings and varied in age from juvenile
      to adult. The majority of teeth were available for examination (95.7%); 3.8% of
      teeth were artefactually absent, 0.4% deemed absent due to acquired tooth loss
      and 0.1% were congenitally absent. Acquired tooth loss was associated
      significantly with sex (P = 0.004) with males having more tooth loss than females
      and total ante-mortem tooth loss was associated significantly with age (P
      <0.0001) with adults having more tooth loss than young adults and juveniles.
      Eleven teeth were malformed and 81 teeth were observed to have two roots.
      Supernumerary teeth (usually maxillary molar teeth) were associated with 1.3% of
      teeth, some specimens demonstrating up to four supernumerary teeth. Thirteen
      persistent deciduous teeth were identified. A total of 713 specimens showed
      attrition or abrasion, with 42.4% of teeth affected. A significant association
      was detected between sex and incidence of abrasion and age and the incidence of
      abrasion (P <0.0001 for both associations). Males showed more abrasion than
      females and adults showed more abrasion than young adults or juveniles. Two
      hundred and sixteen fractured teeth were observed, with root fractures being most
      prevalent. Fractures were associated significantly with sex and with age (P
      <0.0001 for each association). Males had more fractures than females and adults
      had more fractures than young adults and juveniles. Bony changes consistent with
      periodontitis were found, affecting 19.4% of teeth. Males were shown to have more
      periodontitis than females and adults were shown to have more periodontitis than
      young adults and juveniles. Sixty-three periapical lesions were noted.

PMID- 24725511
TI  - Depression in primary TKA and higher medical comorbidities in revision TKA are
      associated with suboptimal subjective improvement in knee function.
AB  - BACKGROUND: To characterize whether medical comorbidities, depression and anxiety
      predict patient-reported functional improvement after total knee arthroplasty
      (TKA). METHODS: We analyzed the prospectively collected data from the Mayo Clinic
      Total Joint Registry for patients who underwent primary or revision TKA between
      1993-2005. Using multivariable-adjusted logistic regression analyses, we examined
      whether medical comorbidities, depression and anxiety were associated with
      patient-reported subjective improvement in knee function 2- or 5-years after
      primary or revision TKA. Odds ratios (OR), along with 95% confidence intervals
      (CI) and p-value are presented. RESULTS: We studied 7,139 primary TKAs at 2- and
      4,234 at 5-years; and, 1,533 revision TKAs at 2-years and 881 at 5-years. In
      multivariable-adjusted analyses, we found that depression was associated with
      significantly lower odds of 0.5 (95% confidence interval [CI]: 0.3 to 0.9; p =
      0.02) of 'much better' knee functional status (relative to same or worse status)
      2 years after primary TKA. Higher Deyo-Charlson index was significantly
      associated with lower odds of 0.5 (95% CI: 0.2 to 1.0; p = 0.05) of 'much better'
      knee functional status after revision TKA for every 5-point increase in score.
      CONCLUSIONS: Depression in primary TKA and higher medical comorbidity in revision
      TKA cohorts were associated with suboptimal improvement in index knee function.
      It remains to be seen whether strategies focused at optimization of medical
      comorbidities and depression pre- and peri-operatively may help to improve TKA
      outcomes. Study limitations include non-response bias and the use of diagnostic
      codes, which may be associated with under-diagnosis of conditions.

PMID- 24725512
TI  - Results of clipping surgery for aneurysmal subarachnoid hemorrhage in the ninth
      and tenth decades of life.
AB  - This study investigated the outcome of clipping surgery for ruptured aneurysms in
      patients older than 80 years of age. From 1988 to 2011 data were retrospectively
      reviewed, and 196 patients treated with clipping obliteration for aneurysmal
      subarachnoid hemorrhage were identified. Patients were divided into two age
      groups of 80-84 and ? 85 years old. The Glasgow Outcome Scale score was assessed
      at discharge and classified as favorable (good recovery or moderate recovery) or
      unfavorable (severe disability, vegetative state, or dead). Radiological and
      clinical characteristics were compared between the two groups. A favorable
      outcome was achieved in 106 (54.1%) of the 196 patients. Preoperative grade and
      Fisher grade were significantly associated with unfavorable outcome, but age was
      not. Based on logistic regression analysis, poor preoperative grade and ruptured
      anterior cerebral artery aneurysm were the predictors of unfavorable outcome, but
      advanced age (? 85 years old) was not. Advanced age itself did not affect the
      outcome of the elderly patients who underwent clipping surgery for aneurysmal
      subarachnoid hemorrhage.

PMID- 24725513
TI  - Comment on: family caregivers in public tertiary care hospitals in Bangladesh:
      risks and opportunities for infection control.

PMID- 24725514
TI  - Two unrelated episodes of Bacillus cereus bacteremia in a neonatal intensive care
      unit.

PMID- 24725515
TI  - The use of real-time feedback via wireless technology to improve hand hygiene
      compliance.
AB  - BACKGROUND: Hand hygiene (HH) is widely regarded as the most effective preventive
      measure for health care-associated infection. However, there is little robust
      evidence on the best interventions to improve HH compliance or whether a
      sustained increase in compliance can reduce rates of health care-associated
      infection. METHODS: To evaluate the effectiveness of a real-time feedback to
      improve HH compliance in the inpatient setting, we used a quasiexperimental study
      comparing the effect of real-time feedback using wireless technology on
      compliance with HH. The study was conducted in two 20-bed step-down units at a
      private tertiary care hospital. Phase 1 was a 3-month baseline period in which HH
      counts were performed by electronic handwash counters. After a 1-month washout
      period, a 7-month intervention was performed in one step-down unit while the
      other unit served as a control. RESULTS: HH, as measured by dispensing episodes,
      was significantly higher in the intervention unit (90.1 vs 73.1 dispensing
      episodes/patient-day, respectively, P = .001). When the intervention unit was
      compared with itself before and after implementation of the wireless technology,
      there was also a significant increase in HH after implementation (74.5 vs 90.1
      episodes/patient-day, respectively, P = .01). There was also an increase in mean
      alcohol-based handrub consumption between the 2 phases (68.9 vs 103.1 mL/patient
      day, respectively, P = .04) in the intervention unit. CONCLUSION: We demonstrated
      an improvement in alcohol gel usage via implementation of real-time feedback via
      wireless technology.

PMID- 24725517
TI  - Six to success: improving primary care management of pediatric overweight and
      obesity.
AB  - INTRODUCTION: Despite the existence of established guidelines addressing
      pediatric obesity, many primary care providers fail to successfully implement
      recommendations. This study measured the impact of Six to Success, a weight
      management program based on the Chronic Care Model, on primary care provider
      adherence to pediatric weight management guidelines. METHOD: We used
      comprehensive pre- and postimplementation chart audits (N = 396) to conduct a
      quality improvement study at a hospital-based pediatric outpatient clinic. Charts
      of patients with a body mass index percentile at or above the 85th percentile
      (preimplementation, n = 90; postimplementation, n = 97) were audited for 23
      identification, assessment, and prevention measures recommended in the care of
      the pediatric overweight/obese patient. RESULTS: Statistically significant
      improvements to clinical guideline adherence were found in the following areas:
      correct diagnosis, physical examination, lifestyle assessment, use of
      motivational interviewing, and prevention strategies. DISCUSSION: These findings
      suggest that Six to Success can be an effective method of improving primary care
      provider adherence to established pediatric weight management guidelines.

PMID- 24725516
TI  - Risk factors and outcomes of infections caused by extremely drug-resistant gram
      negative bacilli in patients hospitalized in intensive care units.
AB  - BACKGROUND: Extremely drug-resistant gram-negative bacilli (XDR-GNB) increasingly
      cause health care-associated infections (HAIs) in intensive care units (ICUs).
      METHODS: A matched case-control (1:2) study was conducted from February 2007 to
      January 2010 in 16 ICUs. Case and control subjects had HAIs caused by GNB
      susceptible to <=1 antibiotic versus >=2 antibiotics, respectively. Logistic and
      Cox proportional hazards regression assessed risk factors for HAIs and predictors
      of mortality, respectively. RESULTS: Overall, 103 case and 195 control subjects
      were enrolled. An immunocompromised state (odds ratio [OR], 1.55; P = .047) and
      exposure to amikacin (OR, 13.81; P < .001), levofloxacin (OR, 2.05; P = .005), or
      trimethoprim-sulfamethoxazole (OR, 3.42; P = .009) were factors associated with
      XDR-GNB HAIs. Multiple factors in both case and control subjects significantly
      predicted increased mortality at different time intervals after HAI diagnosis. At
      7 days, liver disease (hazard ratio [HR], 5.52), immunocompromised state (HR,
      3.41), and bloodstream infection (HR, 2.55) predicted mortality; at 15 days, age
      (HR, 1.02 per year increase), liver disease (HR, 3.34), and immunocompromised
      state (HR, 2.03) predicted mortality; and, at 30 days, age (HR, 1.02 per 1-year
      increase), liver disease (HR, 3.34), immunocompromised state (HR, 2.03), and
      hospitalization in a medical ICU (HR, 1.85) predicted mortality. CONCLUSION: HAIs
      caused by XDR-GNB were associated with potentially modifiable factors. Age, liver
      disease, and immunocompromised state, but not XDR-GNB HAIs, were associated with
      mortality.

PMID- 24725518
TI  - [Modal failure analysis and effects in the detection of errors in the transport
      of samples to the clinical laboratory].
AB  - OBJECTIVE: Owing to the decrease in values of biochemical glucose parameter in
      some samples from external extraction centres, and the risk this implies to
      patient safety; it was decided to apply an adaptation of the "Health Services
      Failure Mode and Effects Analysis" (HFMEA) to manage risk during the pre
      analytical phase of sample transportation from external centres to clinical
      laboratories. MATERIALS AND METHODS: A retrospective study of glucose parameter
      was conducted during two consecutive months. The analysis was performed in its
      different phases: to define the HFMEA topic, assemble the team, graphically
      describe the process, conduct a hazard analysis, design the intervention and
      indicators, and identify a person to be responsible for ensuring completion of
      each action. RESULTS: The results of glucose parameter in one of the transport
      routes, were significantly lower (P=.006). The errors and potential causes of
      this problem were analysed, and criteria of criticality and detectability were
      applied (score>=8) in the decision tree. It was decided to: develop a document
      management system; reorganise extractions and transport routes in some centres;
      quality control of the sample container ice-packs, and the time and temperature
      during transportation. CONCLUSIONS: This work proposes quality indicators for
      controlling time and temperature of transported samples in the pre-analytical
      phase. Periodic review of certain laboratory parameters can help to detect
      problems in transporting samples. The HFMEA technique is useful for the clinical
      laboratory.

PMID- 24725519
TI  - Leadership: reflections over the past 100 years.
AB  - Leadership, viewed by the American Dietetic Association as the ability to inspire
      and guide others toward building and achieving a shared vision, is a much written
      about topic. Research on leadership has addressed the topic using many different
      approaches, from a very simplistic definition of traits to a more complex process
      involving interactions, emotions, and learning. Thousands of books and papers
      have been published on the topic of leadership. This review paper will provide
      examples of the varying foci of the writings on this topic and includes
      references for instruments used to measure leadership traits and behaviors.
      Research is needed to determine effective strategies for preparing dietitians to
      be effective leaders and assume leadership positions. Identifying ways to help
      dietitians better reflect on their leadership experiences to enhance their
      learning and leadership might be one strategy to explore. 

PMID- 24725520
TI  - Dietetics students perceive themselves as leaders and report they demonstrate
      leadership in a variety of contexts.
AB  - A leadership survey was designed and administered to undergraduate dietetics
      students (n=283) at eight universities to examine leadership actions reported
      most frequently, the context of these leadership actions, and students' reported
      perceptions of themselves as leaders. The majority of students perceive
      themselves as leaders in all context areas. The leadership practice, "Enabling
      Others to Act," was the most frequently reported. There were no significant
      differences in leadership behaviors based on college classification status and
      supervisory experience. Leadership behaviors were more prevalent in students who
      had previous leadership coursework, were older, or who had previous leadership
      experience. Dietetics students perceive they demonstrate leadership and do so in
      a variety of contexts, most frequently in class. Therefore, classroom activities
      may help strengthen leadership abilities of future dietetics professionals. 

PMID- 24725521
TI  - Appreciative leadership.

PMID- 24725522
TI  - The reality in leadership.

PMID- 24725523
TI  - Leadership in nutrition and dietetics: today's wisdom for tomorrow's leaders.

PMID- 24725524
TI  - Constructive developmental theory: an alternative approach to leadership.

PMID- 24725525
TI  - Learning to lead: developing dietetics leaders.

PMID- 24725526
TI  - Leadership development: preparing dietetics professionals for success.

PMID- 24725527
TI  - Servant leadership: helping people make wise choices.

PMID- 24725528
TI  - Leadership with a little "l".

PMID- 24725529
TI  - "L" is for "leadership".

PMID- 24725530
TI  - Are we training leaders? Conversations with three leaders.

PMID- 24725531
TI  - Cosinor-based rhythmometry.
AB  - A brief overview is provided of cosinor-based techniques for the analysis of time
      series in chronobiology. Conceived as a regression problem, the method is
      applicable to non-equidistant data, a major advantage. Another dividend is the
      feasibility of deriving confidence intervals for parameters of rhythmic
      components of known periods, readily drawn from the least squares procedure,
      stressing the importance of prior (external) information. Originally developed
      for the analysis of short and sparse data series, the extended cosinor has been
      further developed for the analysis of long time series, focusing both on rhythm
      detection and parameter estimation. Attention is given to the assumptions
      underlying the use of the cosinor and ways to determine whether they are
      satisfied. In particular, ways of dealing with non-stationary data are presented.
      Examples illustrate the use of the different cosinor-based methods, extending
      their application from the study of circadian rhythms to the mapping of broad
      time structures (chronomes). 

PMID- 24725532
TI  - Clinical impact of intra-aortic balloon pump during extracorporeal life support
      in patients with acute myocardial infarction complicated by cardiogenic shock.
AB  - BACKGROUND: There is no available data on clinical outcome in patients with acute
      myocardial infarction (AMI) complicated by cardiogenic shock who are supported by
      an intra-aortic balloon pump (IABP) in combination with extracorporeal life
      support (ECLS). METHODS: We analysed 96 consecutive patients with AMI and
      complicating cardiogenic shock who were assisted by an ECLS system between
      January 2004 and December 2011. The primary outcome was in-hospital mortality.
      The secondary outcomes were the success rate of weaning from ECLS and the lactate
      clearance for 48 hours (%). RESULTS: A combination of IABP and ECLS was used in
      41 (42.7%) patients. In-hospital mortality occurred for 51 patients (ECLS with
      IABP versus ECLS alone; 51.2% vs. 54.5%, p = 0.747). The success rate of weaning
      from ECLS was similar between the two groups (63.4% vs. 58.2%, p = 0.604).
      Complications such as ischemia of a lower extremity or bleeding at the ECLS
      insertion site (p = 0.521 and p = 0.667, respectively) did not increase when ECLS
      was combined with IABP. Among patients who survived for 24 hours after
      intervention, lactate clearance was not significantly different between patients
      who received ECLS alone and those who received ECLS with IABP (p = 0.918).
      CONCLUSIONS: The combined use of ECLS and IABP did not improve in-hospital
      survival in patients with AMI complicated by cardiogenic shock.

PMID- 24725533
TI  - Case of round pneumonia: pulmonary infarct and a rare situation that is similar
      with the lung cancer.
AB  - BACKGROUND AND AIMS: Round pneumonia (RP) is a rare radiological presentation of
      a subtype of lobar pneumonia that arises because of a developmental defect in
      connective tissues (pores of Kohn and channels of Lambert). The round appearance
      on chest X-ray (CXR) is thought to occur from an infectious process that spreads
      from small peripheral alveoli centrifugally through interalveolar channels via
      the pores of Kohn and the canals of Lambert. This explains the nonsegmental
      distribution and shape of RP. The pathogenesis of RP is unknown. An alternative
      theory holds that RP in children occurs because of underdeveloped pores of Kohn
      and the absence of canals of Lambert, limiting the spread of the organism and
      resulting in a focal, round mass seen on radiographs. As a result of this
      developmental defect, dissemination of infection remains in a limited area. While
      this is a well-known entity in childhood, it has been described infrequently in
      adults. Lesions of RP are not necessarily round; oval lesions can also be seen.
      It is a radiological subtype of the pneumonia subtype and presents as a solitary
      nodule or a mass lesion in CXR. METHODS: We presented two cases of RP. One
      mimicked and was mistaken for pulmonary infarction because of triangular pleural
      based density and the other mimicked pulmonary malignancy because of a
      homogeneous triangular opacity based on the pleura on the posteroanterior
      radiography and computed tomography. CONCLUSION: These cases were presented
      because of RP's importance, and RP should be considered a part of differential
      diagnosis of pulmonary infarct and lung tumor.

PMID- 24725535
TI  - Cloning and expression analysis of a transformer gene in Daphnia pulex during
      different reproduction stages.
AB  - The full-length cDNA of a transformer gene (Dptra) was cloned from the cladoceran
      Daphnia pulex using RACE. Dptra expression was assessed by qPCR and whole-mount
      in situ hybridization in different reproductive stages. The Dptra cDNA, 1652bp in
      length, has a 1158-bp open reading frame that encodes a 385 amino acid
      polypeptide containing one Sex determination protein N terminal (SDP_N)
      superfamily, eight putative phosphorylation sites, and an arginine-serine (RS)
      rich domain at the N-terminus. Dptra showed 81%, 53%, 51% and 45% identity to
      orthologous genes in Daphnia magna, Apis mellifera, Apis cerana and Bombus
      terrestris, respectively. Phylogenetic analysis based on deduced amino acid
      sequences revealed that Dptra clustered in the hymenopteran clade and was most
      closely related to D. magna and A. mellifera. qPCR showed that Dptra expression
      increased significantly (P<0.05) in different reproductive stages in the
      following order: male, ephippial female, parthenogenetic female, resting egg and
      juvenile female. Dptra expression is significantly different between males and
      females and it is significantly greater in ephippial females and males than in
      parthenogenetic D. pulex (with summer eggs). Whole-mount in situ hybridization
      revealed that Dptra was expressed at different levels between males and females.
      In males, hybridization signals were found in the first antennae, second antennae
      and thoracic limb, whereas expression levels in the corresponding sites of
      parthenogenetic and ephippial females were relatively weak. This suggests that
      the Dptra gene plays significant roles in switching modes of reproduction and in
      sexual differentiation. 

PMID- 24725534
TI  - Clinical validation of the EndoPredict test in node-positive, chemotherapy
      treated ER+/HER2- breast cancer patients: results from the GEICAM 9906 trial.
AB  - INTRODUCTION: EndoPredict (EP) is an RNA-based multigene test that predicts the
      likelihood of distant recurrence in patients with estrogen receptor-positive
      (ER+), human epidermal growth factor receptor 2-negative (HER2-) breast cancer
      (BC) who are being treated with adjuvant endocrine therapy. Herein we report the
      prospective-retrospective clinical validation of EP in the node-positive,
      chemotherapy-treated, ER+/HER2- BC patients in the GEICAM 9906 trial. METHODS:
      The patients (N = 1,246) were treated either with six cycles of fluorouracil,
      epirubicin and cyclophosphamide (FEC) or with four cycles of FEC followed by
      eight weekly courses of paclitaxel (FEC-P), as well as with endocrine therapy if
      they had hormone receptor-positive disease. The patients were assigned to EP risk
      categories (low or high) according to prespecified cutoff levels. The primary
      endpoint in the clinical validation of EP was distant metastasis-free survival
      (MFS). Metastasis rates were estimated using the Kaplan-Meier method, and
      multivariate analysis was performed using Cox regression. RESULTS: The molecular
      EP score and the combined molecular and clinical EPclin score were successfully
      determined in 555 ER+/HER2- tumors from the 800 available samples in the GEICAM
      9906 trial. On the basis of the EP, 25% of patients (n = 141) were classified as
      low risk. MFS was 93% in the low-risk group and 70% in the high-risk group
      (absolute risk reduction = 23%, hazard ratio (HR) = 4.8, 95% confidence interval
      (CI) = 2.5 to 9.5; P < 0.0001). Multivariate analysis showed that, in this
      ER+/HER2- cohort, EP results are an independent prognostic parameter after
      adjustment for age, grade, lymph node status, tumor size, treatment arm, ER and
      progesterone receptor (PR) status and proliferation index (Ki67). Using the
      predefined EPclin score, 13% of patients (n = 74) were assigned to the low-risk
      group, who had excellent outcomes and no distant recurrence events (absolute risk
      reduction vs high-risk group = 28%; P < 0.0001). Furthermore, EP was prognostic
      in premenopausal patients (HR = 6.7, 95% CI = 2.4 to 18.3; P = 0.0002) and
      postmenopausal patients (HR = 3.3, 95% CI = 1.3 to 8.5; P = 0.0109). There were
      no statistically significant differences in MFS between treatment arms (FEC vs
      FEC-P) in either the high- or low-risk groups. The interaction test results
      between the chemotherapy arm and the EP score were not significant. CONCLUSIONS:
      EP is an independent prognostic parameter in node-positive, ER+/HER2- BC patients
      treated with adjuvant chemotherapy followed by hormone therapy. EP did not
      predict a greater efficacy of FEC-P compared to FEC alone.

PMID- 24725536
TI  - Association between the presence of protein bands in ram seminal plasma and sperm
      tolerance to freezing.
AB  - This study evaluated associations between the presence of protein bands in ram
      seminal plasma and the quality of sperm frozen with distinct extenders.
      Ejaculates were frozen in a Tris-egg yolk based extender, including either 5%
      glycerol or 100mM trehalose. Seminal plasma samples were submitted to
      unidimensional electrophoresis. Pre-freezing and post-thawing sperm quality was
      similar between extenders (P>0.05). A total of 26 bands were identified in ram
      seminal plasma. Pre-freezing sperm motility was increased when the 15, 19 and
      80kDa bands were present in seminal plasma (P<0.05). The presence of an 11kDa
      band in seminal plasma was associated with reduced pre-freezing membrane
      integrity (P<0.05). After thawing, both sperm motility and membrane integrity
      were reduced when a 24kDa band was present in seminal plasma (P<0.05). Post
      thawing acrosome integrity was greater in the presence of a 31kDa band in seminal
      plasma (P<0.05). Regardless of the cryoprotectant included in the freezing
      extender, these six bands may be potential markers for ram sperm tolerance to
      freezing. 

PMID- 24725537
TI  - Nutrition, metabolic profiles and puberty in Brahman (Bos indicus) beef heifers.
AB  - The aim of the present study was to gain an improved understanding of the
      relationships between body weight (BW), body condition (BCS), and metabolic
      homeostasis, and the attainment of puberty in Brahman heifers in a subtropical
      environment. Brahman heifers (200+/-3kg BW; 2.00+/-0.0 BCS) were assigned to a
      moderate nutrition (MN, n=11) or improved nutrition (IN, n=11) treatment from 11
      to 23 months-of-age. The heifers were monitored at regular intervals for
      circulating concentrations of GH, IGF-1, insulin, glucose and leptin, and ovarian
      follicular activity was recorded until the first ovulation. From approximately 16
      months of age, heifers on IN had a greater (P<0.01) BW and greater (P<0.01) BCS
      than heifers on MN. Heifers on IN also had a generally improved metabolic
      homeostasis than heifers on MN which was reflected in greater circulating
      concentrations of insulin, leptin, IGF-1 and glucose in the former heifers.
      Heifers on IN attained puberty between 21 and 23 months of age and only one
      heifer on MN had reached puberty by 23 months. This study has shown that Brahman
      heifers on IN had a metabolic homeostasis that was supportive of reproductive
      maturation and puberty. 

PMID- 24725538
TI  - Complete clinical regression of a BRAF V600E-mutant pediatric glioblastoma
      multiforme after BRAF inhibitor therapy.
AB  - BACKGROUND: Standard therapies for high grade glioma have failed to substantially
      improve survival and are associated with significant morbidity. At relapse, high
      grade gliomas, such as glioblastoma multiforme, are refractory to therapy and
      universally fatal. BRAF V600E-mutations have been described in a modest 6% to 7%
      of primary central nervous system (CNS) tumors, but with increased prevalence in
      the pediatric population and in certain brain tumor subtypes. The use of BRAF
      inhibitors have transformed melanoma therapy however their use in brain tumors
      remains unproven. CASE PRESENTATION: We describe the pediatric case of a now 12
      year old Caucasian male who originally presented at age 9 with a right fronto
      parietal glioblastoma multiforme that recurred 2 1/2 years from diagnosis.
      Molecular analysis of the primary tumor revealed a BRAF V600E mutation and the
      patient was placed on the BRAF inhibitor vemurafenib. A complete response was
      observed after 4 months of therapy and remains sustained at 6 months. CONCLUSION:
      This is the first report of a complete response of relapsed glioblastoma
      multiforme to targeted BRAF inhibitor therapy. While not a predominant mutation
      in glioblastoma multiforme, the increased prevalence of BRAF V600 mutations in
      pediatric CNS tumors and certain subtypes marks a population to whom this therapy
      could be applied. Response to this therapy suggests that BRAF inhibitors can
      affect primary CNS lesions when a documented and targetable mutation is present.

PMID- 24725539
TI  - Orphan receptor GPR15/BOB is up-regulated in rheumatoid arthritis.
AB  - Chemokine receptors on leukocytes mediate the recruitment and accumulation of
      these cells within affected joints in chronic inflammatory diseases such as
      rheumatoid arthritis (RA). Identification of involved receptors offers potential
      for development of therapeutic interventions. The objective of this study was to
      investigate the expression of orphan receptor GPR15/BOB in the synovium of RA and
      non-RA patients and in peripheral blood of RA patients and healthy donors.
      GPR15/BOB protein and messenger RNA expression were examined in RA and non-RA
      synovium by immunofluorescence and reverse-transcription polymerase chain
      reaction (RT-PCR) respectively. GPR15/BOB expression on peripheral blood
      leukocytes was analysed by flow cytometry and GPR15/BOB messenger RNA was
      examined in peripheral blood monocytes by RT-PCR. GPR15/BOB protein was observed
      in CD68+ and CD14+ macrophages in synovia, with greater expression in RA synovia.
      GPR15/BOB protein was expressed in all patient synovia whereas in non-RA synovia
      expression was low or absent. Similarly GPR15/BOB messenger RNA was detected in
      all RA and a minority of non-RA synovia. GPR15/BOB protein was expressed on
      peripheral blood leukocytes from RA and healthy individuals with increased
      expression by monocytes and neutrophils in RA. GPR15/BOB messenger RNA expression
      was confirmed in peripheral blood monocytes. In conclusion GPR15/BOB is expressed
      by macrophages in synovial tissue and on monocytes and neutrophils in peripheral
      blood, and expression is up-regulated in RA patients compared to non-RA controls.
      This orphan receptor on monocytes/macrophages and neutrophils may play a role in
      RA pathophysiology. 

PMID- 24725540
TI  - IL6-174 G/C gene polymorphism and its relation to serum IL6 in Egyptian children
      with community-acquired pneumonia.
AB  - Cytokines are involved in the pathogenesis of community acquired pneumonia (CAP).
      The aim of this study is to investigate the association of IL6-174 G/C gene
      polymorphism with CAP in Egyptian children, to assess its effect on CAP outcome
      and to determine its effect on the serum IL6 levels in these children. IL6-174
      G/C gene polymorphism was genotyped in 210 Egyptian children (100 patients with
      CAP and 110 healthy controls) using PCR-RFLP, while the serum IL6 levels were
      measured by ELISA method. We found a significant association between the GG
      genotype, G allele of IL6-174 G/C SNP and susceptibility to CAP (P=0.02, 0.01
      respectively). However, GG genotype and G allele were protective against severe
      sepsis (p=0.004), acute respiratory failure (p<0.001) and hospital mortality
      (p<0.001). Serum IL6 levels were significantly increased in these children while
      there was no relation between GG genotype and serum IL6. In conclusion, IL6-174
      G/C gene polymorphism may contribute to susceptibility to CAP in Egyptian
      children. 

PMID- 24725541
TI  - An increase of interleukin-33 serum levels after coronary stent implantation is
      associated with coronary in-stent restenosis.
AB  - The study aim was to determine the predictive value of interleukin (IL)-33, a
      recently described member of the IL-1 family of cytokines, for the development of
      in-stent restenosis (ISR). IL-33 serum levels were measured in 387 consecutive
      patients undergoing percutaneous coronary intervention (PCI) of whom 193 had
      stable angina, 93 non-ST elevation myocardial infarction (NSTEMI), and 101 ST
      elevation MI (STEMI), respectively. Blood was taken directly before and 24h after
      stent implantation. The presence of ISR was initially evaluated by clinical means
      after six to eight months. When presence of myocardial ischemia was suspected,
      coronary angiography was performed to confirm the suspected diagnosis of ISR.
      Clinical ISR was present in total in 34 patients (8.8%). IL-33 was detectable in
      185 patients and was below detection limit in 202 patients. In patients with
      decreased IL-33 (n=95), unchanged or non-detectable levels (n=210) or increased
      levels of IL-33 after PCI (n=82), ISR-rate was 2.1%, 9.5% and 14.6%, respectively
      (p<0.05). Accordingly, patients with ISR showed a significant increase of IL-33
      upon PCI (p<0.05). This association was independent from clinical presentation
      and risk factors as well as numbers and type of stents. In patients with both
      stable and unstable coronary artery disease, an increase of IL-33 serum levels
      after stent implantation is associated with a higher rate of in-stent restenosis.

PMID- 24725542
TI  - Comparison of interleukin-6 and matrix metalloproteinase expression in the
      subretinal fluid and the vitreous during proliferative vitreoretinopathy:
      correlations with extent, duration of RRD and PVR grade.
AB  - INTRODUCTION: The full extent of IL-6 involvement in PVR pathophysiology has not
      yet been comprehensively investigated. The aim of this study was the comparison
      of the IL-6 effect on MMP expression between SRF and the vitreous in the context
      of RRD complicated by PVR. MATERIALS AND METHODS: Thirty-one SRF samples from 31
      eyes of 31 consecutive patients suffering from RRD with PVR were collected during
      treatment by scleral buckling. Twenty-eight vitreous samples from 28 eyes of 28
      RRD patients with PVR were collected during surgical management with pars plana
      vitrectomy (PPV). Enzyme Linked Immunosorbent Assay was employed for the
      measurement of MMP-1, -3, -8 and TIMP-1 concentrations (in ng/ml). MMP
      gelatinolytic activity was determined with the use of gelatin zymography analysis
      using sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE).
      RESULTS: Correlation analysis in the SRF revealed a significant correlation
      between MMP-1/IL6 and RRD duration. Regression analysis in the SRF revealed a
      significant correlation between the MMP-9/IL-6 and RRD extent. In the same fluid,
      with respect to PVR grade, ANOVA revealed a significant relationship with the
      proMMP-2/IL-6, MMP-2/IL6 and TIMP-1/IL-6 ratios. Graphical representation of the
      results revealed that, between the SRF and vitreous groups, significant peak
      values were observed for all MMP/IL-6 and TIMP-1/IL-6 ratios included in this
      study with the exception of the MMP-2/IL-6 ratio. CONCLUSIONS: It appears that
      there is a significant correlation between the presence of IL-6 and MMP/TIMP
      ratio in the SRF, indicating that IL-6 may contribute to the increased MMP/TIMP
      ratio during PVR.

PMID- 24725544
TI  - An interesting trichloracetic acid injury in a patient with psychiatric disorder.

PMID- 24725543
TI  - Highly purified mussel adhesive protein to secure biosafety for in vivo
      applications.
AB  - BACKGROUND: Unique adhesive and biocompatibility properties of mussel adhesive
      proteins (MAPs) are known for their great potential in many tissue engineering
      and biomedical applications. Previously, it was successfully demonstrated that
      redesigned hybrid type MAP, fp-151, mass-produced in Gram-negative bacterium
      Escherichia coli, could be utilized as a promising adhesive biomaterial. However,
      purification of recombinant fp-151 has been unsatisfactory due to its adhesive
      nature and polarity which make separation of contaminants (especially,
      lipopolysaccharide, a toxic Gram-negative cell membrane component) very
      difficult. RESULTS: In the present work, we devised a high resolution
      purification approach to secure safety standards of recombinant fp-151 for the
      successful use in in vivo applications. Undesirable impurities were remarkably
      eliminated as going through sequential steps including treatment with multivalent
      ion and chelating agent for cell membrane washing, mechanical cell disruption,
      non-ionic surfactant treatment for isolated inclusion body washing, acid
      extraction of washed inclusion body, and ion exchange chromatography purification
      of acid extracted sample. Through various analyses, such as high performance
      liquid chromatographic purity assay, limulus amoebocyte lysate endotoxin assay,
      and in vitro mouse macrophage cell tests on inflammation, viability,
      cytotoxicity, and apoptosis, we confirmed the biological safety of bacterial
      derived purified recombinant fp-151. CONCLUSIONS: Through this purification
      design, recombinant fp-151 achieved 99.90% protein purity and 99.91% endotoxin
      reduction that nearly no inflammation response was observed in in vitro
      experiments. Thus, the highly purified recombinant MAP would be successfully used
      as a safety-secured in vivo bioadhesive for tissue engineering and biomedical
      applications.

PMID- 24725545
TI  - Publication stratification.

PMID- 24725546
TI  - Effect of sampling and diagnostic effort on the assessment of schistosomiasis and
      soil-transmitted helminthiasis and drug efficacy: a meta-analysis of six drug
      efficacy trials and one epidemiological survey.
AB  - It is generally recommended to perform multiple stool examinations in order to
      improve the diagnostic accuracy when assessing the impact of mass drug
      administration programmes to control human intestinal worm infections and
      determining efficacy of the drugs administered. However, the collection and
      diagnostic work-up of multiple stool samples increases costs and workload. It has
      been hypothesized that these increased efforts provide more accurate results when
      infection and drug efficacy are summarized by prevalence (proportion of subjects
      infected) and cure rate (CR, proportion of infected subjects that become egg
      negative after drug administration), respectively, but not when these indicators
      are expressed in terms of infection intensity and egg reduction rate (ERR). We
      performed a meta-analysis of six drug efficacy trials and one epidemiological
      survey. We compared prevalence and intensity of infection, CR and ERR based on
      collection of one or two stool samples that were processed with single or
      duplicate Kato-Katz thick smears. We found that the accuracy of prevalence
      estimates and CR was lowest with the minimal sampling effort, but that this was
      not the case for estimating infection intensity and ERR. Hence, a single Kato
      Katz thick smear is sufficient for reporting infection intensity and ERR
      following drug treatment.

PMID- 24725552
TI  - Spanish adaptation of the European guidelines for the evaluation and treatment of
      actinic keratosis.
AB  - Current trends in our setting indicate that the prevalence of actinic keratosis
      and similar diseases will increase in coming years and impose a greater burden on
      health care resources. A long list of clinical features must be taken into
      account when approaching the treatment of actinic keratosis. Until recently,
      therapeutic approaches focused solely on ablative procedures and the treatment of
      individual lesions and did not take into account areas of field cancerization.
      Now that the therapeutic arsenal has grown, standardized criteria are needed to
      guide the optimal choice of treatment for each patient. The elaboration of
      evidence-based consensus recommendations for the diagnosis and treatment of
      actinic keratosis generates knowledge that will help clinicians to deliver the
      highest level of care possible, standardizing decision-making processes and
      enhancing awareness among all the health professionals involved in the care
      pathway. 

PMID- 24725554
TI  - Health care consumption and costs due to foot and ankle injuries in the
      Netherlands, 1986-2010.
AB  - BACKGROUND: Foot and ankle injuries account for a large proportion of Emergency
      Department attendance. The aim of this study was to assess population-based
      trends in attendances due to foot and ankle injuries in the Netherlands since
      1986, and to provide a detailed analysis of health care costs in these patients.
      METHODS: Age- and gender-standardized emergency attendance rates and incidence
      rates for hospital admission were calculated for each year of the study. Injury
      cases and hospital length of stay were extracted from the National Injury
      Surveillance System (non-hospitalized patients) and the National Medical
      Registration (hospitalized patients). Data were grouped into osseous and
      ligamentous injuries for foot and ankle separately. An incidence-based cost model
      was applied to calculate associated direct health care costs. RESULTS: Since 1986
      the overall emergency attendance rate decreased from 858 to 640 per 100,000
      person years. In non-admitted patients (90% of cases), ligamentous injuries
      approximately halved, whereas osseous injuries increased by 28% (foot) and 25%
      (ankle). The incidence rate for hospital admission increased by 35%, mainly due
      to an almost doubling of osseous injuries. Attendance rates showed a peak in
      adolescents and adults until ~45 years of age in males and (less pronounced) in
      females. The total number of hospital days decreased to 58,708 days in 2010.
      Hospital length of stay (HLOS) increased with age and was highest for osseous
      injuries. HLOS was unaffected by gender, apart for longer stay in elderly females
      with an osseous ankle injury. Health care costs per case were highest for osseous
      injuries of the ankle (? 3,461). Costs were higher for females and increased with
      age to ? 6,023 in elderly males and ? 10,949 in elderly females. Main cost
      determinants were in-hospital care (56% of total costs), rehabilitation/nursing
      care (15%), and physical therapy (12%). CONCLUSIONS: Since 1986, the emergency
      attendance rate of foot and ankle injuries in the Netherlands decreased by 25%.
      Throughout the years, the attendance rate of (relatively simple) ligamentous
      injuries strongly reduced, whereas osseous injuries nearly doubled. Attendance
      rates and health care costs were gender- and age-related. Main cost determinants
      were in-hospital care, rehabilitation/nursing care, and physical therapy.

PMID- 24725555
TI  - Differences in regulatory T-cell and dendritic cell pattern in decidual tissue of
      placenta accreta/increta cases.
AB  - INTRODUCTION: Primary infertility, miscarriage, and preeclampsia have been
      correlated with reduced numbers of regulatory T-cells (Treg) suggesting that
      decreased extravillous trophoblast (EVT) invasion originates from inadequate EVT
      tolerance. In contrast increased numbers of Treg-cells may be responsible for
      over-invasion of EVT. As the maturation status of dendritic cells (DC) influences
      T-cell behavior (tolerance or immune activation), altered relation between
      immature and mature DCs may also influence EVT invasion. METHOD: Paraffin
      embedded specimens of placenta accreta/increta (Pc; n = 11) and healthy
      intrauterine pregnancy (IUG; n = 18) were double-stained for cytokeratin and
      CD45, CD68, CD56, CD20, CD3, or CD8 as well as FoxP3/CD4 and FoxP3/CD8 and single
      stained for CD4, CD25, FoxP3, CD209, Dec205 and CD83. Quantification of the
      leukocyte subpopulations was performed for decidua parietalis and basalis as
      characterized by cytokeratin-positive EVT. Statistical analysis was performed by
      using the Mann-Whitney test. RESULT: There were significantly fewer CD4(+) cells
      in Pc than in IUG. Concerning the Treg-markers, FoxP3(+) cells are significantly
      increased. CD25(+) cells showed a small non-significant increase in Pc in
      comparison to IUG. Concerning dendritic cells, immature non-activated CD209(+)
      DCs were significantly decreased in Pc while immature activated CD205(+) DCs were
      slightly but non-significantly increased. Mature activated CD83(+) DC were non
      significantly decreased in IUG vs Pc. DISCUSSION AND CONCLUSION: The increased
      number of Treg-cells in Pc suggests significance for these cells in the
      regulation of trophoblast invasion. Their adequate interaction with other
      lymphocyte populations (e.g. adequately maturated dendritic cells) may be one
      mechanism to assure controlled EVT invasion.

PMID- 24725556
TI  - Functional genomics annotation of a statistical epistasis network associated with
      bladder cancer susceptibility.
AB  - BACKGROUND: Several different genetic and environmental factors have been
      identified as independent risk factors for bladder cancer in population-based
      studies. Recent studies have turned to understanding the role of gene-gene and
      gene-environment interactions in determining risk. We previously developed the
      bioinformatics framework of statistical epistasis networks (SEN) to characterize
      the global structure of interacting genetic factors associated with a particular
      disease or clinical outcome. By applying SEN to a population-based study of
      bladder cancer among Caucasians in New Hampshire, we were able to identify a set
      of connected genetic factors with strong and significant interaction effects on
      bladder cancer susceptibility. FINDINGS: To support our statistical findings
      using networks, in the present study, we performed pathway enrichment analyses on
      the set of genes identified using SEN, and found that they are associated with
      the carcinogen benzo[a]pyrene, a component of tobacco smoke. We further carried
      out an mRNA expression microarray experiment to validate statistical genetic
      interactions, and to determine if the set of genes identified in the SEN were
      differentially expressed in a normal bladder cell line and a bladder cancer cell
      line in the presence or absence of benzo[a]pyrene. Significant nonrandom sets of
      genes from the SEN were found to be differentially expressed in response to
      benzo[a]pyrene in both the normal bladder cells and the bladder cancer cells. In
      addition, the patterns of gene expression were significantly different between
      these two cell types. CONCLUSIONS: The enrichment analyses and the gene
      expression microarray results support the idea that SEN analysis of bladder in
      population-based studies is able to identify biologically meaningful statistical
      patterns. These results bring us a step closer to a systems genetic approach to
      understanding cancer susceptibility that integrates population and laboratory
      based studies.

PMID- 24725557
TI  - Generic substitution of antiepileptics: need for a balanced view.
AB  - There is considerable interest and debate concerning the place of generic
      substitution, especially relating to antiepileptic drugs (AEDs). Sadly, one of
      the causes of the ongoing debate is confusion, often intentionally fueled by the
      pharmaceutical industry among health professionals and patients regarding the
      regulatory determination of bioequivalence. Few understand the correct
      definition. It is often erroneously stated that to be considered bioequivalent
      there is an allowed difference in the extent and rate of absorption of 80% to
      125% between a generic drug product and the branded standard. This is false and
      implies that there is a wide leniency allowed, with varying clinical outcomes
      probable. This myth needs to be countered to ensure the safety of patients. A
      balanced review of the issues surrounding the generic substitution of AEDs is
      presented. 

PMID- 24725558
TI  - High dosage of aripiprazole induced priapism: a case report.

PMID- 24725559
TI  - Tuberculosis risk and anti-tumour necrosis factor agents in rheumatoid arthritis:
      a critical appraisal of national registry data.
AB  - Tuberculosis (TB) remains a major global health problem. In patients with
      rheumatoid arthritis (RA), the risk of reactivation of latent TB infection (LTBI)
      is increased and treatment with tumour necrosis factor (TNF) antagonists further
      increases this risk. However, interpretation of results describing comparative TB
      risk during therapy with different TNF antagonists is difficult. This is not only
      a result of different patient ethnic groups and background TB rates, but also
      because of differing methods of data acquisition. This paper offers a critical
      appraisal of registry data pertaining to RA patients treated with different anti
      TNF agents, focusing on methodological approaches that may limit the
      generalizability of findings or invalidate the direct comparison of TB risk
      between different national registries. Underlying factors that can make data
      interpretation challenging are discussed, including differences in methods for TB
      diagnosis or data collection and reporting, as well as background TB risk. The
      introduction of special monitoring systems, such as prospective multinational
      registries, to strengthen surveillance and better quantify the extent of under
      reporting is required, especially in countries where the background TB risk is
      high. 

PMID- 24725560
TI  - Neglected tropical diseases: becoming less neglected.

PMID- 24725561
TI  - Sound advice for public health.

PMID- 24725562
TI  - A new direction for hepatitis C.

PMID- 24725563
TI  - Nephrology in developing countries: the ISN's story.

PMID- 24725564
TI  - Expression of concern: the SCIPIO trial.

PMID- 24725566
TI  - Diana Farmer: pioneer of fetal surgery.

PMID- 24725567
TI  - Mental health services in South Sudan.

PMID- 24725568
TI  - Africans in south China face social and health barriers.

PMID- 24725569
TI  - Vitamin D supplements and bone mineral density.

PMID- 24725570
TI  - Vitamin D supplements and bone mineral density.

PMID- 24725571
TI  - Vitamin D supplements and bone mineral density.

PMID- 24725572
TI  - Vitamin D supplements and bone mineral density - Authors' reply.

PMID- 24725573
TI  - Vitamin D supplements and bone mineral density.

PMID- 24725574
TI  - HPV-based screening for prevention of invasive cervical cancer.

PMID- 24725575
TI  - HPV-based screening for prevention of invasive cervical cancer.

PMID- 24725576
TI  - Cognitive behaviour therapy for health anxiety.

PMID- 24725577
TI  - HPV-based screening for prevention of invasive cervical cancer - Authors' reply.

PMID- 24725578
TI  - Founding of the Global Health Film initiative.

PMID- 24725579
TI  - Commotio cordis: a case of ventricular fibrillation caused by a cricket ball
      strike to the chest.

PMID- 24725580
TI  - A population-based study of childhood respiratory morbidity after severe lower
      respiratory tract infections in early childhood.
AB  - OBJECTIVES: To estimate the risk of childhood chronic respiratory morbidity among
      those hospitalized for severe lower respiratory tract infection (LRTI) in early
      childhood, and to determine whether severe LRTI is an independent predictor.
      STUDY DESIGN: The population-based Regie de l'Assurance Maladie du Quebec
      datasets were used to identify LRTI hospitalizations before age 2 years in a
      birth cohort from 1996-1997 and a comparison cohort of children without an LRTI
      hospitalization. The incidence rate and incidence rate ratio of chronic
      respiratory morbidity before age 10 years were calculated, and multivariable
      logistic regression was performed to estimate the impact of LRTI hospitalization
      on chronic respiratory morbidity. Population-attributable risks of chronic
      respiratory morbidity due to severe LRTI were estimated, and similar analyses
      were performed for respiratory syncytial virus LRTI. RESULTS: Among the birth
      cohort, 7104 patients (4.9%) were hospitalized for LRTI before age 2 years. By
      age 10 years, 52.5% of the LRTI cohort and 27.9% of the nonhospitalized cohort
      had developed chronic respiratory morbidity; the incidence rate ratio was 1.81
      (95% CI, 1.76-1.86) for males and 1.91 (95% CI, 1.84-1.99) for females. The OR
      for chronic respiratory morbidity based on LRTI hospitalization before age 2
      years was 2.79 (95% CI, 2.66-2.93). The population-attributable risk of chronic
      respiratory morbidity due to any LRTI was approximately 25%, and that for
      respiratory syncytial virus LRTI was similar. CONCLUSIONS: Hospitalization of
      young children for LRTIs is associated with two-fold increased risk of childhood
      chronic respiratory morbidity, demonstrating the ongoing impact of LRTI in
      infancy.

PMID- 24725581
TI  - Ultrasonography of the colon in pediatric ulcerative colitis: a prospective,
      blind, comparative study with colonoscopy.
AB  - OBJECTIVES: To evaluate the usefulness of colonic ultrasonography (US) in
      assessing the extent and activity of disease in pediatric ulcerative colitis (UC)
      and to compare US findings with clinical and endoscopic features. STUDY DESIGN:
      Consecutive pediatric patients (n = 60) with a diagnosis of UC and suspected
      disease flare-up were prospectively enrolled; of these, 50 patients were eligible
      for the study. All underwent clinical evaluation, bowel US with color Doppler
      examination and colonoscopy. Blind US was performed the day before endoscopy in
      all patients. The US assessed variables were bowel wall thickness >3 mm, bowel
      wall stratification, vascularity, presence of haustra coli, and enlarged
      mesenteric lymph nodes. RESULTS: The endoscopic extent of disease was
      independently confirmed in 47 patients by US that yielded a 90% concordance with
      endoscopy (95% CI 0.82-0.96). Multiple regression analysis showed that US
      measurements with an independent predictive value of severity at endoscopy were
      increased bowel wall thickness (P < .0008), increased vascularity (P < .002),
      loss of haustra (P = .031), and loss of stratification of the bowel wall (P =
      .021). Each variable was assigned a value of 1 if present. The US score strongly
      correlated with clinical (r = 0.94) and endoscopic activity (r = 0.90) of disease
      (P < .0001). CONCLUSIONS: Colonic US is a useful first line noninvasive tool to
      assess the extent and activity of disease in children with UC and to estimate the
      severity of a flare-up, prior to further invasive tests.

PMID- 24725583
TI  - Ewing's sarcoma: A rarity in sinonasal region.

PMID- 24725584
TI  - Initial experience with the Sophono Alpha 1 osseointegrated implant.
AB  - In the last several years, bone anchored hearing aids have proven to be useful in
      treating conductive and mixed unilateral or bilateral hearing loss, as well as
      for sensorineural unilateral hearing loss. The Sophono Alpha 1 model has the
      advantage of not requiring an abutment, with it being coupled by magnetism
      instead. We report the cases of 3 infants with congenital malformations of
      external and middle ear. Audiometry showed conductive hearing loss. All 3
      patients were implanted with Alpha 1 model (Sophono). Patients evolved
      satisfactorily. After 30 days we applied the processor and the control audiometry
      showed a marked improvement of hearing thresholds, although without a complete
      closure of the gap. With minimal care, the skin over the implant remained in
      excellent condition, with a very satisfactory cosmetic outcome. 

PMID- 24725585
TI  - [Clinical and radiological evolution of a group of untreated acoustic neuromas].
AB  - INTRODUCTION: The acoustic neuroma is a benign tumour that originates in the
      vestibular branch of the eighth cranial nerve. The main treatment is surgery, but
      many authors suggest that with elderly patients or in small neuromas we can opt
      for watchful waiting. METHODS: This was a retrospective study from 2007 to 2013
      that included 27 patients diagnosed of acoustic neuroma that had not been treated
      due to the size of the tumour, age and comorbidities, or by patient choice. We
      evaluated overall condition, hearing thresholds, degree of canal paresis and
      central disorders. RESULTS: After 6 years of follow up, clinical manifestations
      of 18 patients remained unchanged, 5 patients underwent hearing loss and
      developed tinnitus, 2 cases had more intense tinnitus and 2 cases had dizziness.
      The radiological controls by magnetic resonance imaging showed that the initial
      maximum diameters (5-16mm) increased by 1.7mm on average, with annual growth
      rates below 0.5mm. CONCLUSION: In selected cases, such as for small neuromas and
      in elderly patients, the conservative option of close monitoring with magnetic
      resonance imaging is an important alternative given that, in our cases, clinical
      features and radiological image did not suffer major changes. If there were any
      such changes, therapeutic options could be proposed.

PMID- 24725586
TI  - [Peculiarities in the development of the superior semicircular canal].
AB  - OBJECTIVE: Our objective was to study the ontogeny of the superior semicircular
      canal in order to describe its peculiarities. METHODS: We analyzed 76 series of
      human embryos aged between 32 days (6mm) and newborns. The samples were cut
      serially and stained using Martin's trichrome technique. RESULTS: In semicircular
      canal development there were a number of peculiarities, such as: a defined
      chronological sequence of osteogenesis with a variable rate of ossification; the
      fact that each nucleus of ossification was involved in the formation of one of
      its covers (the upper in the superficial and the lower in the deep); the
      appearance of transitory dehiscence; and canal closure by means of bone with
      laminar pattern, with a minimum thickness of 0.1mm. CONCLUSION: The peculiarities
      in canal development could explain the origin of pathological dehiscence in the
      canal, whether congenital or acquired.

PMID- 24725587
TI  - Temporal bone myeloid sarcoma.

PMID- 24725588
TI  - Phytochrome controls conidiation in response to red/far-red light and daylight
      length and regulates multistress tolerance in Beauveria bassiana.
AB  - Phytochromes (Phy) in filamentous fungi are Group VIII histidine kinases that
      share a unique N-terminal photosensory core, but their functions are largely
      unknown. Here we show that Beauveria bassiana Phy (Bbphy) is functionally vital
      for growth, conidiation and multistress tolerance of the fungal entomopathogen
      lacking sexual stage. Colony growth of DeltaBbphy was significantly slower in a
      nutrition-rich medium but faster in several minimal media. Conidial yield of
      DeltaBbphy in the rich medium increased at the fitted rate of 3.4 * 10(7) conidia
      h(-1) white light in the light/dark cycles of 0:24 to 16:8 h, decreased greatly
      in the short-, long- and full-day cycles of red/far-red light, but was unaffected
      under full-day blue light. Moreover, DeltaBbphy showed higher osmosensitivity,
      increased antioxidant capability, and decreased conidial thermotolerance and UV-B
      resistance, accompanied with downregulation of Hog1 phosphorylation and of four
      Hog1-related genes under osmotic stress, and upregulation of five superoxide
      dismutases and four catalases under oxidative stress. All the changes were
      restored by the gene complementation. Taken together, Bbphy controls conidiation
      by responding to daylight length and red/far-red light and regulates multistress
      responses perhaps because of an involvement in Hog1 pathway. Our findings
      highlight diverse functions of Bbphy in B. bassiana.

PMID- 24725589
TI  - Computational study of effects of tension imbalance on phonation in a three
      dimensional tubular larynx model.
AB  - OBJECTIVES: The present study explores the use of a continuum-based computational
      model to investigate the effect of left-right tension imbalance on vocal fold
      (VF) vibrations and glottal aerodynamics, as well as its implication on
      phonation. The study allows us to gain new insights into the underlying physical
      mechanism of irregularities induced by VF tension imbalance associated with
      unilateral cricothyroid muscle paralysis. METHODS: A three-dimensional simulation
      of glottal flow and VF dynamics in a tubular laryngeal model with tension
      imbalance was conducted by using a coupled flow-structure interaction
      computational model. Tension imbalance was modeled by reducing by 20% the Young's
      modulus of one of the VFs, while holding VF length constant. Effects of tension
      imbalance on vibratory characteristic of the VFs and on the time-varying
      properties of glottal airflow as well as the aerodynamic energy transfer are
      comprehensively analyzed. RESULTS AND CONCLUSIONS: The analysis demonstrates that
      the continuum-based biomechanical model can provide a good description of
      phonatory dynamics in tension imbalance conditions. It is found that although 20%
      tension imbalance does not have noticeable effects on the fundamental frequency,
      it does lead to a larger glottal flow leakage and asymmetric vibrations of the
      two VFs. A detailed analysis of the energy transfer suggests that the majority of
      the energy is consumed by the lateral motion of the VFs and the net energy
      transferred to the softer fold is less than the one transferred to the normal
      fold.

PMID- 24725590
TI  - Effect of lower limb malalignment in the frontal plane on transverse plane
      mechanics during gait in young individuals with varus knee alignment.
AB  - BACKGROUND: Varus knee alignment has been identified as a risk factor for the
      progression of medial knee osteoarthritis (OA). This study tested the hypothesis
      that not only frontal plane kinematics and kinetics but also transverse plane
      lower extremity mechanics during gait are affected by varus malalignment of the
      knee. METHODS: Eighteen, otherwise healthy children and adolescents with varus
      malalignment of the knee were studied to examine the association between static
      varus malalignment and functional gait parameters. Kinematic data were collected
      using a Vicon motion capture system (Vicon Motion Systems, Oxford, UK). Two AMTI
      force plates (Advanced Mechanical Technology, Inc., Watertown, MA, USA) were used
      to collect kinetic data. RESULTS: The results indicated that changes in
      transverse plane mechanics occur concomitantly with changes in knee malalignment
      in the frontal plane. A mechanical consequence of varus knee malalignment is
      obviously an increased endorotation of the foot (internal foot placement) and an
      increased internal knee rotation (tibia rotation) during stance phase. The linear
      correlation between the maximum external knee adduction moment in terminal stance
      and the internal knee rotation in terminal stance (r=0.823, p<0.001) shows that
      this transverse plane gait mechanics is directly in conjunction with intrinsic
      compressive load on the medial compartment during gait. CONCLUSIONS:
      Understanding factors that influence dynamic knee joint loading in healthy, varus
      malaligned knees may help us to identify risk factors that lead to OA. Thus,
      three-dimensional gait analysis could be used for clinical prognoses regarding
      the onset or progression of medial knee OA.

PMID- 24725591
TI  - Knee biomechanics during popular recreational and daily activities in older men.
AB  - BACKGROUND: Physical activity is recommended for older adults, including those
      with knee pathology. However, demands on the knee during popular recreational
      activities are unclear. The study purpose was to determine knee biomechanics in
      healthy older men during golf and bowling and compare them to activities of daily
      living. METHODS: Three-dimensional motion analysis was used to determine knee
      biomechanics in 19 healthy males (45-73 years): 11 golfers and eight bowlers.
      Subjects performed walking, stair ascent, stair descent, and either golf or
      bowling. Comparisons were made between the recreational activity and activities
      of daily living. RESULTS: During bowling, flexion angle at peak extensor moment
      was as high as during stair descent, and peak extensor moment was as high as
      during stair ascent. For the golf lead knee, flexion angle at peak extensor
      moment and peak extensor moment were as high as during stair ascent, and peak
      abduction moment, internal and external rotation angles were larger than during
      all activities of daily living. Peak external rotation angle for the golf trail
      knee was larger than all activities of daily living. CONCLUSION: The greatest
      challenge for the knee of healthy older males during bowling is eccentric control
      of knee flexion. Golf poses challenges in all three planes of motion for the lead
      knee and in the transverse plane for the trail knee. CLINICAL RELEVANCE:
      Comparing mechanical demands on the knee during bowling and golf to those of
      stair negotiation provides a reference for clinicians when recommending
      recreational activities for older adults with knee pathology.

PMID- 24725592
TI  - Regulating the ribosome: a spotlight on RNA dark matter.
AB  - In this issue, Pircher et al. (2014) show that an abundant ribosome-associated 18
      nt noncoding RNA (ncRNA), derived from the open reading frame of an mRNA, acts
      directly on the ribosome and regulates global translation levels in response to
      hypertonic shock. 

PMID- 24725582
TI  - Respiratory outcomes of the surfactant positive pressure and oximetry randomized
      trial (SUPPORT).
AB  - OBJECTIVE: To explore the early childhood pulmonary outcomes of infants who
      participated in the National Institute of Child Health and Human Development's
      Surfactant Positive Airway Pressure and Pulse Oximetry Randomized Trial
      (SUPPORT), using a factorial design that randomized extremely preterm infants to
      lower vs higher oxygen saturation targets and delivery room continuous positive
      airway pressure (CPAP) vs intubation/surfactant. STUDY DESIGN: The Breathing
      Outcomes Study, a prospective secondary study to the Surfactant Positive Airway
      Pressure and Pulse Oximetry Randomized Trial, assessed respiratory morbidity at 6
      month intervals from hospital discharge to 18-22 months corrected age (CA). Two
      prespecified primary outcomes-wheezing more than twice per week during the worst
      2-week period and cough longer than 3 days without a cold-were compared for each
      randomized intervention. RESULTS: One or more interviews were completed for 918
      of the 922 eligible infants. The incidences of wheezing and cough were 47.9% and
      31.0%, respectively, and did not differ between the study arms of either
      randomized intervention. Infants randomized to lower vs higher oxygen saturation
      targets had a similar risk of death or respiratory morbidity (except for croup
      and treatment with oxygen or diuretics at home). Infants randomized to CPAP vs
      intubation/surfactant had fewer episodes of wheezing without a cold (28.9% vs
      36.5%; P<.05), respiratory illnesses diagnosed by a doctor (47.7% vs 55.2%;
      P<.05), and physician or emergency room visits for breathing problems (68.0% vs
      72.9%; P<.05) by 18-22 months CA. CONCLUSION: Treatment with early CPAP rather
      than intubation/surfactant is associated with less respiratory morbidity by 18-22
      months CA. Longitudinal assessment of pulmonary morbidity is necessary to fully
      evaluate the potential benefits of respiratory interventions for neonates.

PMID- 24725593
TI  - ERQC autophagy: Yet another way to die.
AB  - A novel autophagy pathway eliminates nonnative polytopic membrane proteins from
      the endoplasmic reticulum that evade degradation by the ubiquitin proteasome
      system. 

PMID- 24725594
TI  - Nonenzymatic protein acylation as a carbon stress regulated by sirtuin
      deacylases.
AB  - Cellular proteins are decorated with a wide range of acetyl and other acyl
      modifications. Many studies have demonstrated regulation of site-specific
      acetylation by acetyltransferases and deacetylases. Acylation is emerging as a
      new type of lysine modification, but less is known about its overall regulatory
      role. Furthermore, the mechanisms of lysine acylation, its overlap with protein
      acetylation, and how it influences cellular function are major unanswered
      questions in the field. In this review, we discuss the known roles of
      acetyltransferases and deacetylases and the sirtuins as a conserved family of a
      nicotinamide adenine dinucleotide (NAD+)-dependent protein deacylases that are
      important for response to cellular stress and homeostasis. We also consider the
      evidence for an emerging idea of nonenzymatic protein acylation. Finally, we put
      forward the hypothesis that protein acylation is a form of protein "carbon
      stress" that the deacylases evolved to remove as a part of a global protein
      quality-control network.

PMID- 24725595
TI  - Alternative capture of noncoding RNAs or protein-coding genes by herpesviruses to
      alter host T cell function.
AB  - In marmoset T cells transformed by Herpesvirus saimiri (HVS), a viral U-rich
      noncoding (nc) RNA, HSUR 1, specifically mediates degradation of host microRNA-27
      (miR-27). High-throughput sequencing of RNA after crosslinking
      immunoprecipitation (HITS-CLIP) identified mRNAs targeted by miR-27 as enriched
      in the T cell receptor (TCR) signaling pathway, including GRB2. Accordingly,
      transfection of miR-27 into human T cells attenuates TCR-induced activation of
      mitogen-activated protein kinases (MAPKs) and induction of CD69. MiR-27 also
      robustly regulates SEMA7A and IFN-gamma, key modulators and effectors of T cell
      function. Knockdown or ectopic expression of HSUR 1 alters levels of these
      proteins in virally transformed cells. Two other T-lymphotropic gamma
      herpesviruses, AlHV-1 and OvHV-2, do not produce a noncoding RNA to downregulate
      miR-27 but instead encode homologs of miR-27 target genes. Thus, oncogenic gamma
      herpesviruses have evolved diverse strategies to converge on common targets in
      host T cells. 

PMID- 24725596
TI  - Functional consequences of splicing of the antisense transcript COOLAIR on FLC
      transcription.
AB  - Antisense transcription is widespread in many genomes; however, how much is
      functional is hotly debated. We are investigating functionality of a set of long
      noncoding antisense transcripts, collectively called COOLAIR, produced at
      Arabidopsis FLOWERING LOCUS C (FLC). COOLAIR initiates just downstream of the
      major sense transcript poly(A) site and terminates either early or extends into
      the FLC promoter region. We now show that splicing of COOLAIR is functionally
      important. This was revealed through analysis of a hypomorphic mutation in the
      core spliceosome component PRP8. The prp8 mutation perturbs a cotranscriptional
      feedback mechanism linking COOLAIR processing to FLC gene body histone
      demethylation and reduced FLC transcription. The importance of COOLAIR splicing
      in this repression mechanism was confirmed by disrupting COOLAIR production and
      mutating the COOLAIR proximal splice acceptor site. Our findings suggest that
      altered splicing of a long noncoding transcript can quantitatively modulate gene
      expression through cotranscriptional coupling mechanisms. 

PMID- 24725597
TI  - Prognostic and predictive value of cathepsin X in serum from colorectal cancer
      patients.
AB  - BACKGROUND: Cathepsin X is a cysteine protease involved in mechanisms of
      malignant progression. It is secreted from tumour cells as a proenzyme and may
      serve to predict the disease status and risk of death for cancer patients. In a
      previous, pilot, study on 77 colorectal patients we demonstrated the correlation
      of higher serum levels with shorter overall survival. METHODS: 264 patients with
      colorectal cancer were included in a prospectively accrued multi-centre
      observational cohort study with the aim of testing novel biomarkers. Blood
      samples were collected before preoperative large bowel endoscopy and total
      cathepsin X was measured in sera by ELISA. As a control group we selected at
      random 77 subjects who had no findings at endoscopy and reported no co-morbidity.
      RESULTS: The mean level of cathepsin X in cancer patients did not differ from the
      control levels (23.4 ng/ml +/- 6.4 SD vs. 18.8 ng/ml +/- 11.4 SD, p > 0.05) and
      there was no association with age, gender, disease stage, tumour location or CEA.
      In univariate analysis no association between cathepsin X levels and overall
      survival was demonstrated for the entire set of patients, however, cathepsin X
      was associated with survival in a group of patients with local resectable disease
      (stages I-III) (HR = 1.69, 95% CI: 1.03-2.75, p = 0.03). For this group,
      multivariate Cox regression analysis showed an association (HR = 3.13, 95% CI:
      1.37-7.18, p = 0.003) between high cathepsin X levels and shorter overall
      survival for patients who did not receive chemotherapy, whereas, for patients who
      received chemotherapy, there was no association between cathepsin X and survival
      (HR = 0.51, 95% CI: 0.20-1.33, p = 0.88). CONCLUSIONS: Association of cathepsin X
      levels with overall survival was not confirmed for an entire set of 264
      colorectal patients, but for patients in stages I-III with local resectable
      disease. The significant association of cathepsin X with survival in a group of
      patients who received no chemotherapy and the absence of this association in the
      group who received chemotherapy, suggest the possible predictive value for
      response to chemotherapy. The results have to be confirmed in a further
      prospective study.

PMID- 24725598
TI  - Effect of statin therapy on mortality from infection and sepsis: a meta-analysis
      of randomized and observational studies.
AB  - INTRODUCTION: Observational data have suggested that statin therapy may reduce
      mortality in patients with infection and sepsis; however, results from randomized
      studies are contradictory and do not support the use of statins in this context.
      Here, we performed a meta-analysis to investigate the effects of statin therapy
      on mortality from infection and sepsis. METHODS: We searched electronic databases
      (PubMed and Embase) for articles published before November 2013. Randomized or
      observational studies reporting the effects of statin therapy on mortality in
      patients with infection or sepsis were eligible. Randomized and observational
      studies were separately pooled with relative risks (RRs) and random-effects
      models. RESULTS: We examined 5 randomized controlled trials with 867 patients and
      27 observational studies with 337,648 patients. Among the randomized controlled
      trials, statins did not significantly decrease in-hospital mortality (RR, 0.98;
      95% confidence interval (CI), 0.73 to 1.33) or 28-day mortality (RR, 0.93; 95%
      CI, 0.46 to 1.89). However, observational studies indicated that statins were
      associated with a significant decrease in mortality with adjusted data (RR, 0.65;
      95% CI, 0.57 to 0.75) or unadjusted data (RR, 0.74; 95% CI, 0.59 to 0.94).
      CONCLUSIONS: Limited evidence suggests that statins may not be associated with a
      significant reduction in mortality from infection and sepsis. Although meta
      analysis from observational studies showed that the use of statins was associated
      with a survival advantage, these outcomes were limited by high heterogeneity and
      possible bias in the data. Therefore, we should be cautious about the use of
      statins in infection and sepsis.

PMID- 24725599
TI  - A death in the family.

PMID- 24725601
TI  - Post-traumatic ruptured gastrothorax mimicking chylothorax.
AB  - INTRODUCTION: The presence of the stomach in the chest is called gastrothorax.
      Few cases were reported. Most of them were related to congenital diaphragmatic
      hernia. OBJECTIVES: We are presenting a case of successful repair of ruptured
      traumatic gastrothorax which was masqueraded as chylothorax. METHODS: A male
      patient with rupture stomach in the left chest cavity. Results successful repair
      of ruptured traumatic gastrothorax. CONCLUSION: Traumatic ruptured gastrothorax
      can be mistaken for chylothorax.

PMID- 24725600
TI  - Investigation of the essential role of platelet-tumor cell interactions in
      metastasis progression using an agent-based model.
AB  - BACKGROUND: Metastatic tumors are a major source of morbidity and mortality for
      most cancers. Interaction of circulating tumor cells with endothelium, platelets
      and neutrophils play an important role in the early stages of metastasis
      formation. These complex dynamics have proven difficult to study in experimental
      models. Prior computational models of metastases have focused on tumor cell
      growth in a host environment, or prediction of metastasis formation from clinical
      data. We used agent-based modeling (ABM) to dynamically represent hypotheses of
      essential steps involved in circulating tumor cell adhesion and interaction with
      other circulating cells, examine their functional constraints, and predict
      effects of inhibiting specific mechanisms. METHODS: We developed an ABM of Early
      Metastasis (ABMEM), a descriptive semi-mechanistic model that replicates
      experimentally observed behaviors of populations of circulating tumor cells,
      neutrophils, platelets and endothelial cells while incorporating representations
      of known surface receptor, autocrine and paracrine interactions. Essential
      downstream cellular processes were incorporated to simulate activation in
      response to stimuli, and calibrated with experimental data. The ABMEM was used to
      identify potential points of interdiction through examination of dynamic outcomes
      such as rate of tumor cell binding after inhibition of specific platelet or tumor
      receptors. RESULTS: The ABMEM reproduced experimental data concerning neutrophil
      rolling over endothelial cells, inflammation-induced binding between neutrophils
      and platelets, and tumor cell interactions with these cells. Simulated platelet
      inhibition with anti-platelet drugs produced unstable aggregates with frequent
      detachment and re-binding. The ABMEM replicates findings from experimental models
      of circulating tumor cell adhesion, and suggests platelets play a critical role
      in this pre-requisite for metastasis formation. Similar effects were observed
      with inhibition of tumor integrin alphaV/beta3. These findings suggest that anti
      platelet or anti-integrin therapies may decrease metastasis by preventing stable
      circulating tumor cell adhesion. CONCLUSION: Circulating tumor cell adhesion is a
      complex, dynamic process involving multiple cell-cell interactions. The ABMEM
      successfully captures the essential interactions necessary for this process, and
      allows for in-silico iterative characterization and invalidation of proposed
      hypotheses regarding this process in conjunction with in-vitro and in-vivo
      models. Our results suggest that anti-platelet therapies and anti-integrin
      therapies may play a promising role in inhibiting metastasis formation.

PMID- 24725602
TI  - Pitfalls in optical on-line monitoring for high-throughput screening of microbial
      systems.
AB  - BACKGROUND: New high-throughput screening systems for microbial systems, e.g. the
      BioLector technology, are simple to handle and offer various options of optical
      online measurements. The parallelization and small scale in microtiter plates
      allow economical high throughput and, hence, to screen many parameters in
      reasonable time. Fluorescent proteins as fluorescent tags made the tracking of
      cellular proteins in-vivo a routine task. All these tools significantly
      contribute to the understanding of bioprocesses. But, there are some pitfalls
      which might mislead the user of such techniques. RESULTS: In this work the
      bacterium E. coli and the yeast K. lactis expressing the recombinant fluorescent
      proteins GFP, YFP, FbFP and mCherry were investigated. Cultivations were
      performed applying special microtiter plates with optodes for dissolved oxygen
      tension (DOT) and pH measurement in the BioLector system. In this way, microbial
      growth, protein formation, DOT and pH were monitored on-line via optical signals.
      During these studies it became obvious that fluorescent proteins can interfere
      with the optical signals leading to incorrect results. In this work these effects
      are characterized in detail and possibilities are presented how such adverse
      effects can be corrected or minimized by mathematical procedures or modification
      of the measuring method. Additionally, it is shown that morphological changes of
      cells can affect the biomass on-line monitoring via scattered light. CONCLUSIONS:
      The here reported phenomena refer to typical experiments in biotechnological
      labs. For this reason these aspects are highlighted in this work to make
      operators of such valuable techniques as the BioLector aware for potential
      pitfalls and resulting misinterpretations. With the right approach it is possible
      to minimize existing problems and deal with them.

PMID- 24725603
TI  - Diabetic foot infection treatment and care.
AB  - Foot infections in diabetic patients are a common, complex and costly problem.
      They are potentially adverse with progression to deeper spaces and tissues and
      are associated with severe complications. The management of diabetic foot
      infection (DFI) requires a prompt and systematic approach to achieve more
      successful outcomes and to ultimately avoid amputations. This study reviews a
      multi-step treatment for DFIs. Between September 2010 and September 2012, a total
      of about 37 patients were consulted for DFI. The treatment algorithm included
      four steps, that is, several types of debridement according to the type of wound,
      the application of negative pressure therapy (NPT), other advanced dressings, a
      targeted antibiotic therapy local or systemic as the case may, and, if necessary,
      reconstructive surgery. This treatment protocol showed excellent outcomes,
      allowing us to avoid amputation in most difficult cases. Only about 8% of
      patients require amputation. This treatment protocol and a multidisciplinary
      approach with a specialised team produced excellent results in the treatment of
      DFI and in the management of diabetic foot in general, allowing us to improve the
      quality of life of diabetic patients and also to ensure cost savings. 

PMID- 24725605
TI  - Changing social contact patterns under tropical weather conditions relevant for
      the spread of infectious diseases.
AB  - Weather conditions and social contact patterns provide some clues to
      understanding year-round influenza epidemics in the tropics. Recent studies
      suggest that contact patterns may direct influenza transmission in the tropics as
      critically as the aerosol channel in temperate regions. To examine this argument,
      we analysed a representative nationwide survey dataset of contact diaries with
      comprehensive weather data in Taiwan. Methods we used included model-free
      estimated relative changes in reproduction number, R 0; relative changes in the
      number of contacts; and model-based estimated relative changes in mean contacts
      using zero-inflated negative binomial regression models. Overall, social contact
      patterns clearly differ by demographics (such as age groups), personal
      idiosyncrasies (such as personality and happiness), and social institutions (such
      as the division of weekdays and weekend days). Further, weather conditions also
      turn out to be closely linked to contact patterns under various circumstances.
      Fleeting contacts, for example, tend to diminish when it rains hard on weekdays,
      while physical contacts also decrease during weekend days with heavy rain.
      Frequent social contacts on weekdays and under good weather conditions, including
      high temperature and low absolute humidity, all might facilitate the transmission
      of infectious diseases in tropical regions.

PMID- 24725604
TI  - The prevalence of coronary anomalies in a single center of Korea: origination,
      course, and termination anomalies of aberrant coronary arteries detected by ECG
      gated cardiac MDCT.
AB  - BACKGROUND: Coronary anomalies are rare congenital abnormalities often found
      incidentally on conventional coronary angiography (CCA) or coronary CT
      angiography (CTA). They may result in various clinical outcomes. CCA is invasive
      and not able to demonstrate all coronary anomalies in detail, especially those
      with complex courses. Multidetector computed tomography (MDCT) enables
      visualization of the origin and course of coronary arteries. The objective of
      this study was to investigate the prevalence of origin and termination coronary
      artery anomalies and the course of these anomalies in patients in a single center
      in Korea. METHODS: To diagnose coronary anomalies, the angiographic data of 8,864
      consecutive patients undergoing 64- or 320-MDCT from September 2005 to November
      2011 were analyzed retrospectively. RESULTS: Among the 8,864 patients, 103
      (1.16%) had coronary anomalies. Ninety (87.4%) patients had origin and
      distribution anomalies, and 13 (12.6%) patients had a coronary artery fistula.
      The most common anomaly (41, 39.8%) was an anomalous origin of the right coronary
      artery (RCA). Of these, three patients received a coronary artery bypass graft.
      CONCLUSIONS: The prevalence of coronary anomalies in a single center of Korea was
      1.16%. The incidence and patterns of coronary artery anomalies in our patient
      population were similar to those of previous studies.

PMID- 24725607
TI  - [Meckel's diverticulum mimicking Crohn's disease].

PMID- 24725606
TI  - Bony destructive injuries of the calcaneus: long-term results of a minimally
      invasive procedure followed by early functional exercise: a retrospective study.
AB  - BACKGROUND: Bony destructive injury of the calcaneus (BDIC) represents one of the
      most severe comminuted fractures of the calcaneus in which soft tissue coverage
      remains intact. The features of this injury include a collapsed articular
      surface, significant widening, severe loss of height and an unrecognisable
      outline of the calcaneus. This study aims to present the long-term outcomes of
      BDIC treated in a minimally invasive fashion followed by supervised early
      exercise. METHODS: Twelve patients with unilateral BDICs were treated at our
      institution. The main surgical procedures included percutaneous traction and
      leverage reduction and internal compression fixation with anatomic plates and
      compression bolts. Early functional exercise was encouraged to mould the subtalar
      joint. The height, length and width of the calcaneus; Bohler's and Gissane's
      angles; reduction of the articular surfaces; and functional recovery of the
      affected feet were assessed. RESULTS: The height, length and width of the
      calcaneus were substantially restored. The mean Bohler's and Gissane's angles of
      the affected calcaneus were 24.5 and 122.8 degrees, respectively. Five patients
      regained anatomical or nearly anatomical reduction of their posterior facets.
      Residual articular displacement of more than 3 mm was noted in three patients.
      Patients were followed for a mean of 93.9 months. The mean American Orthopaedic
      Foot and Ankle Society score was 83.8. Nine patients showed excellent or good
      results. Radiographic evidence of post-traumatic subtalar arthritis was observed
      in four cases. However, no subtalar arthrodesis was required. CONCLUSIONS: BDICs
      can be treated effectively with percutaneous reduction and internal compression
      fixation followed by early active exercise. This protocol resulted in
      satisfactory radiological and functional outcomes.

PMID- 24725608
TI  - [What is the utility of proton pump inhibitor testing in non-cardiac chest
      pain?].
AB  - BACKGROUND AND AIMS: Noncardiac chest pain (NCCP) often represents a diagnostic
      and therapeutic challenge. Given that gastroesophageal reflux disease (GERD) is
      the most common cause of NCCP, initial treatment with proton-pump inhibitors
      (PPI) has been proposed for all patients (PPI testing), reserving esophageal
      function testing solely for non-responders. The aim of the present study was to
      provide evidence on the clinical utility of PPI testing with high-dose
      pantoprazole in patients with NCCP. PATIENTS AND METHODS: We carried out a study
      of diagnostic performance with a cohort design in patients with NCCP, who had
      been assessed by the Cardiology Service. All patients underwent upper endoscopy,
      esophageal manometry, and 24h esophageal pH monitoring before PPI testing with
      pantoprazole 40 mg every 12h for 1 month. Before and after treatment, we assessed
      the severity (intensity and frequency) of chest pain, quality of life, and
      anxiety and depression by means of specific questionnaires. The diagnosis of GERD
      was based on a pathological finding of esophageal pH monitoring. A positive
      response to PPI testing was defined as an improvement in chest pain >50% compared
      with the baseline score after 1 month of PPI therapy. RESULTS: We included 30
      consecutive patients (17 men/13 women) with a mean age of 49 years. Of these 30
      patients, 20 with NCCP had GERD (67%, 95%CI: 47%-83%). A positive response to PPI
      therapy was observed in 13 of the 30 (43%) patients with NCCP: 11 of the 20 (55%)
      patients in the GERD-positive group and 2 of the 10 (20%) in the GERD-negative
      group. The sensitivity, specificity, positive predictive value, negative
      predictive value, and accuracy of PPI testing was 55%, 80%, 85%, 47% and 63%,
      respectively. A significant reduction in chest pain after pantoprazole therapy
      (P=.003) and a slight non significant improvement in anxiety and depression was
      achieved in the GERD-positive group as compared to the GERD-negative group.
      CONCLUSIONS: In NCCP, PPI testing with pantoprazole has a low sensitivity for the
      diagnosis of GERD, placing in doubt the strategy of reserving functional study to
      non-responders to antisecretory therapy. Esophageal function testing and accurate
      diagnosis would allow appropriate targeted therapy for all patients with NCCP.

PMID- 24725609
TI  - A novel way of treating mallet finger injuries.
AB  - Standard treatment protocols following a mallet finger injury involve lengthy
      periods of immobilization in an effort to ensure the terminal extensor tendon is
      able to maintain the distal interphalangeal joint in extension. This author
      describes a technique that utilizes a combination of an orthosis and kinesiotape,
      thereby creating a treatment protocol that shortens the immobilization phase for
      these patients. - Victoria Priganc, PhD, OTR, CHT, CLT, Practice Forum Editor.

PMID- 24725610
TI  - Symptomatic and asymptomatic interphalageal osteoarthritis: An ultrasonographic
      study.
AB  - OBJECTIVE: To date few studies have examined whether ultrasonography can depict
      morphologic differences in painful and painless osteoarthritis (OA). This study
      describes and compares the clinical, radiographic and ultrasonographic findings
      of patients with both painful and painless proximal interphalgeal (PIP) and/or
      distal interphalgeal (DIP) OA. METHODS: Patients with PIP and/or DIP OA (ACR
      criteria) were prospectively recruited. The clinical rheumatologist chose up to 3
      painful joints and up to 3 painless symmetric joints in each patient to define 2
      cohorts of OA: symptomatic (SG) and asymptomatic (ASG). A conventional postero
      anterior hand x ray was performed and read by one rheumatologist following the
      OARSI atlas, blinded to clinical and sonographic data. Ultrasound (US) was
      performed by an experienced rheumatologist, blinded to both clinical and
      radiographic data in joints previously selected by the clinical rheumatologist.
      US-pathology was assessed as present or absent as defined in previous reports:
      osteophytes, joint space narrowing, synovitis, intra-articular power doppler
      signal, intra-articular bony erosion, and visualization of cartilage.
      Radiographic and ultrasonographic intrareader reliability test was performed.
      RESULTS: A total of 50 joints in the SG and ASG were included from 20 right
      handed women aged 61.85 (46-73) years with PIP and DIP OA diagnosed 6.8 (1-17)
      years ago. 70% SG joints and ASG were right and left sided respectively. The SG
      showed significantly more osteophytes, synovitis and non-visualization of joint
      cartilage. Intrareader radiographic and ultrasonographic agreement was excellent.
      CONCLUSION: This study demonstrates that painful PIP and/or DIP OA have more
      ultrasonographic structural changes and synovitis.

PMID- 24725611
TI  - Prediction of respective contribution of linear electron flow and PGR5-dependent
      cyclic electron flow to non-photochemical quenching induction.
AB  - In chloroplasts, regulated formation of the proton gradient across the thylakoid
      membrane (DeltapH) is important for controlling non-photochemical quenching
      (NPQ), which is crucial for plants to perform photosynthesis under fluctuating
      light conditions. The DeltapH is generated by two electron flows: the linear
      electron flow (LEF) and the cyclic electron flow (CEF). The Arabidopsis CEF
      mutant, pgr5, showed significantly lower NPQ values than those observed in WT,
      indicating that DeltapH, generated by the PGR5-dependent CEF, has a crucial role
      in controlling NPQ. However, the respective significance of LEF and CEF for
      DeltapH formation is largely unknown. Here we applied computer simulation to
      reproduce NPQ induction kinetics and estimate the respective contribution of LEF
      and PGR5-dependent CEF to the dynamics of DeltapH formation. The results indicate
      that the contribution of CEF to total DeltapH formation for induction of NPQ
      varies from 60-80%. The simulation also suggested a role of the PGR5-dependent
      CEF in accelerating electron transfer in the cytochrome b6f complex. 

PMID- 24725612
TI  - Implant-abutment interface: a comparison of the ultimate force to failure among
      narrow-diameter implant systems.
AB  - STATEMENT OF PROBLEM: Limited available alveolar ridge bone and space
      deficiencies are some of the challenging scenarios that have led many dental
      implant manufacturers to develop narrow-diameter implants of various designs.
      Clinicians may have concerns about the durability and function of the narrow
      diameter implants. PURPOSE: The purpose of this study was to explore and compare
      the ultimate failure resistance of the smallest diameter of the 2-stage type
      implant provided by 5 commonly used dental implant systems. MATERIAL AND METHODS:
      Thirty implants, Astra OsseoSpeed 3.0 mm and 3.5 mm, Straumann Bone Level 3.3 mm,
      Zimmer Tapered Screw-Vent 3.7 mm, Full Osseotite Certain 3.25 mm, and NobelSpeedy
      Replace 3.5 mm, 5 of each type, were tested in this study. A rigid clamp was used
      to hold the implants at a 30-degree angle to a static load vector. The load
      continued until the specimen broke or obviously deformed. Peak loads were
      recorded at that point for all the studied implant systems. Student t test and 1
      way ANOVA were used to compare the mean peak load values (alpha=.05). RESULTS:
      The mean fracture/deformation peak load values were 367.20 N +/- 98.05 for Astra
      OsseoSpeed 3.0 mm; 568.80 N +/- 85.24 for Astra OsseoSpeed 3.5 mm; 679.00 N +/-
      81.09 for Full Osseotite Certain 3.25 mm; 553.4 N +/- 56.96 for NobelSpeedy
      Replace 3.5 mm; 802.80 N +/- 134.50 for Zimmer Tapered Screw-Vent 3.7 mm; and
      576.20 N +/- 71.45 for Straumann Bone Level 3.3 mm. Generally, a higher load was
      required to cause failure in implants with larger diameters than in narrower
      diameter implants, and more force was necessary to cause failure in Ti6Al4V alloy
      implants than in commercially pure titanium implants. CONCLUSIONS: With regard to
      implant diameter and ultimate failure strength, Osseotite Certain 3.25 mm was
      considered to be more advantageous in comparison with the other implants tested.

PMID- 24725613
TI  - Use of CAD/CAM to fabricate duplicate abutments for retrofitting an existing
      implant prosthesis: a clinical report.
AB  - Computer-assisted design/computer-assisted manufacturing (CAD/CAM) technology has
      been widely used in the field of dentistry. Among CAD/CAM custom abutments,
      zirconia abutments are becoming more popular due to their favorable mechanical
      and esthetic properties. However, recent review articles show that fractured
      zirconia abutments are a common prosthetic complication. In this clinical report,
      a 72-year-old man presented with a dislodged implant-supported fixed prosthesis
      because of fractured zirconia abutments. This clinical report describes a
      successful application of CAD/CAM technology to fabricate duplicate abutments,
      which were retrofitted to the existing prosthesis. 

PMID- 24725614
TI  - A technique to orient a stone cast in the fabrication of a nasal prosthesis.
AB  - Obtaining the correct orientation of the stone cast in the fabrication of a nasal
      prosthesis is a challenging task. The current technique involves repeated trials
      of the waxed nasal prosthesis on the patient's face to establish its correct
      position. This article proposes a simplified technique to aid in establishing the
      proper orientation of the stone cast in an effort to decrease the number of error
      corrections related to midline discrepancies during the wax sculpting stage. 

PMID- 24725615
TI  - Smile attractiveness of patients treated for congenitally missing maxillary
      lateral incisors as rated by dentists, laypersons, and the patients themselves.
AB  - STATEMENT OF PROBLEM: Esthetic judgments can help dental professionals better
      understand how attentive people are to their own smiles and those of others.
      PURPOSE: The purpose of this study was to evaluate the smile attractiveness of
      patients treated for maxillary lateral incisor agenesis compared with that of
      individuals with a complete dentition. MATERIAL AND METHODS: Photographs were
      made of the smiles of patients with maxillary lateral incisor agenesis who were
      treated with space closure and teeth recontouring (n=26) or space opening and
      implants (n=20) and of a control group with a complete dentition (n=22). Both
      laypersons and dentists assessed smile attractiveness by using a visual analog
      scale. Patients and controls also assessed the level of satisfaction with their
      own smile. Assessments were performed twice, and the reliability of the method
      was determined with Cronbach alpha and intraclass correlation. Multifactorial and
      1-way ANOVA were used to analyze smile attractiveness and participant
      satisfaction, followed by the Bonferroni post hoc test (alpha=.05). RESULTS:
      Attractiveness ratings by dentists and laypersons did not differ significantly
      among the study groups (P=.64). The ratings of male dentists and female
      laypersons differed significantly from those of other evaluators (P=.01).
      Patients with space closure and teeth recontouring were significantly more
      satisfied than controls (P=.002). No significant differences were found between
      the patients with implants and controls or between the patients with implants and
      those with space closure and teeth recontouring. CONCLUSIONS: The smiles of
      patients with maxillary lateral incisor agenesis were judged to be as attractive
      as those of the controls. Male dentists were the most critical raters, closely
      followed by female laypersons. All participants had high levels of satisfaction
      with their own smile; patients treated with space closure and teeth recontouring
      were the most satisfied.

PMID- 24725616
TI  - Insulin lispro low mixture twice daily versus basal insulin glargine once daily
      and prandial insulin lispro once daily in patients with type 2 diabetes requiring
      insulin intensification: a randomized phase IV trial.
AB  - AIMS: To compare the efficacy and safety of two insulin intensification
      strategies in patients with type 2 diabetes inadequately controlled on basal
      insulin glargine with metformin and/or pioglitazone. METHODS: A multinational,
      randomized, open-label trial that compared insulin lispro low mixture (LM25; n =
      236) twice daily with a basal-prandial regimen of insulin glargine once daily and
      insulin lispro once daily (IGL; n = 240) over 24 weeks in patients with HbA1c 7.5
      10.5% and fasting plasma glucose <= 6.7 mmol/l. The primary objective was to
      assess non-inferiority [per-protocol (PP) population], and then superiority
      [intention-to-treat (ITT) population], of LM25 versus IGL according to change in
      HbA1c after 24 weeks (non-inferiority margin 0.4%, two-sided significance level
      0.05). RESULTS: Estimated change [least squares (LS) mean (95% CI)] in HbA1c
      after 24 weeks: -1.30 (-1.44, -1.16)% with LM25 and -1.08 (-1.22, -0.94)% with
      IGL. Non-inferiority was shown [LS mean (95% CI) HbA1c treatment difference -0.21
      (-0.38, -0.04) (PP population)]; gated superiority assessment showed a
      statistically significant advantage for LM25 (p = 0.010; ITT population). Mean
      blood glucose, glycaemic variability, overall tolerability and hypoglycaemic
      episodes per patient-year did not show significant differences between treatments
      during the study. CONCLUSIONS: In patients with type 2 diabetes inadequately
      controlled on once-daily basal insulin glargine and metformin and/or
      pioglitazone, intensification with LM25 was superior to a basal-prandial approach
      in terms of reduction in HbA1c after 24 weeks and did not increase hypoglycaemia
      episodes.

PMID- 24725618
TI  - Reduced hatchability of Anopheles gambiae s.s eggs in presence of third instar
      larvae.
AB  - BACKGROUND: We investigated the hatchability rates of freshly laid Anopheles
      gambiae s.s. eggs in presence of third instars larvae. These experiments were
      conducted using 30 eggs in larval densities of 20, 60 and 100 larvae in
      microcosms. These experiments were designed to evaluate the eggs hatchability in
      habitats with late larvae instars of the same species (experimental) or no larvae
      at all (control). Freshly laid eggs of An.gambiae s.s. were washed in microcosms
      containing larvae of third instars in different three densities (20, 60 and 100)
      and likewise in control microcosms (without larvae). Eggs hatchability was
      monitored twice daily until no more first instar larvae emerged. The numbers of
      first instars larvae were recorded daily and lost eggs were considered preyed
      upon by third instars. FINDINGS: The findings of this study showed that egg
      hatchability was significantly influenced by larval density. CONCLUSION: The
      findings of this study suggest that presence of larvae in habitats may
      significantly reduce hatchability of eggs.

PMID- 24725617
TI  - Strategic Plan for the Spanish Academy of Dermatology and Venerology (AEDV):
      FuturAEDV 2013-2017.
AB  - BACKGROUND: The Spanish Academy of Dermatology and Venereology (AEDV) has decided
      that a Strategic Plan is needed to help the association adapt to new
      circumstances and anticipate future developments. OBJECTIVES: 1) To position the
      AEDV as a medical association that can exert an influence in everything related
      to dermatology. 2) To contribute to the development of the specialty,
      strengthening the prestige and reputation of dermatology and dermatologists. 3)
      To establish a model for operating and strategic thinking that can be handed on
      to successive Boards of Directors and will enable the Academy to identify future
      challenges. METHODS: The approach used to develop the Strategic Plan was as
      follows: analysis of trends in the health care system; assessment of the current
      situation of AEDV and of dermatology in general through an internal analysis
      based on surveys and interviews with academics; analysis of strengths,
      weaknesses, opportunities, and threats; preparation of a mission statement; and
      identification, development, and implementation of a strategy map prioritizing
      strategic lines of action. RESULTS: The strategy map set out 16 general goals
      grouped into 4 main topics (achieving the vision, internal and external
      customers, internal processes, and innovation) and detailed in an action plan
      with 19 initiatives, each with specific actions. The plan will be monitored by
      the Strategic Plan Monitoring Committee, which is made up of the members of the
      Standing Committee and the chairs of the 9 Technical Committees responsible for
      implementing the initiatives. COMMENT: The Functional Plan should guide the
      management of AEDV until 2017, and its implementation will enable the association
      to contribute to the development and prestige of the specialty and position
      itself as a reference in terms of its functional model.

PMID- 24725619
TI  - Mental health correlates of victimization classes among homeless youth.
AB  - Literature reports high rates of street victimization among homeless youth and
      recognizes psychiatric symptoms associated with such victimization. Few studies
      have investigated the existence of victimization classes that differ in type and
      frequency of victimization and how youth in such classes differ in psychiatric
      profiles. We used latent class analysis (LCA) to examine whether classes of
      homeless youth, based on both type and frequency of victimization experiences,
      differ in rates of meeting diagnostic criteria for major depressive episodes and
      posttraumatic stress disorder (PTSD) in a sample of homeless youth (N=601) from
      three regions of the United States. Results suggest youth who experience high
      levels of direct and indirect victimization (high-victimization class) share
      similarly high rates of depressive episodes and PTSD as youth who experience
      primarily indirect victimization only (witness class). Rates of meeting criteria
      for depressive episodes and PTSD were nearly two and three times greater,
      respectively, among the high victimization and witness classes compared to youth
      who never or rarely experienced victimization. Findings suggest the need for
      screening and intervention for homeless youth who report direct and indirect
      victimization and youth who report indirect victimization only, while prevention
      efforts may be more relevant for youth who report limited victimization
      experience. 

PMID- 24725620
TI  - Left ventricular torsional mechanics and myocardial iron load in beta
      thalassaemia major: a potential role of titin degradation.
AB  - BACKGROUND: Iron may damage sarcomeric proteins through oxidative stress. We
      explored the left ventricular (LV) torsional mechanics in patients with beta
      thalassaemia major and its relationship to myocardial iron load. Using HL-1 cell
      and B6D2F1 mouse models, we further determined the impact of iron load on
      proteolysis of the giant sarcomeric protein titin. METHODS AND RESULTS: In 44
      thalassaemia patients aged 25 +/- 7 years and 38 healthy subjects, LV torsion and
      twisting velocities were determined at rest using speckle tracking
      echocardiography. Changes in LV torsional parameters during submaximal exercise
      testing were further assessed in 32 patients and 17 controls. Compared with
      controls, patients had significantly reduced LV apical rotation, torsion,
      systolic twisting velocity, and diastolic untwisting velocity. T2* cardiac
      magnetic resonance findings correlated with resting diastolic untwisting
      velocity. The increments from baseline and resultant LV torsion and systolic and
      diastolic untwisting velocities during exercise were significantly lower in
      patients than controls. Significant correlations existed between LV systolic
      torsion and diastolic untwisting velocities in patients and controls, both at
      rest and during exercise. In HL-1 cells and ventricular myocardium of B6D2F1 mice
      overloaded with iron, the titin-stained pattern of sarcomeric structure became
      disrupted. Gel electrophoresis of iron-overloaded mouse myocardial tissue further
      showed significant decrease in the amount of titin isoforms and increase in titin
      degradation products. CONCLUSIONS: Resting and dynamic LV torsional mechanics is
      impaired in patients with beta-thalassaemia major. Cell and animal models suggest
      a potential role of titin degradation in iron overload-induced alteration of LV
      torsional mechanics.

PMID- 24725622
TI  - Analysis of medical consultation interval between the symptom onset and
      consultation observed in multiple medical facilities in Odate city, Japan,
      2011/2012 and 2012/2013 seasons.
AB  - BACKGROUND: Influenza remains one of the most important causes of respiratory
      infection despite the widespread availability of vaccines. Anti-influenza viral
      agents such as neuraminidase inhibitors are generally efficacious in alleviating
      the symptoms if they are administered within 2 days of the illness onset.
      However, few studies have examined the situation of interval between illness
      onset and medical consultation in influenza outpatients on community level. And
      the predictors or determinants for longer medical consultation interval have not
      been well-defined. MATERIAL AND METHOD: An enhanced surveillance study was
      conducted in Odate city of Japan in 2 consecutive seasons from 2011 to 2013. The
      late consultation rate (>2 days) and its risk factors were investigated in
      confirmed influenza outpatients. RESULTS: A proportion of 5.5% of patients
      visited doctors beyond 2 days of illness onset. Illness onset during non-high
      incidence period, infection with influenza B and being adult or elderly were
      identified as independent risk factors for late consultation and the risk
      increased with the number of risk factors. CONCLUSION: The consultation behavior
      for influenza was generally well in our study population. Identified risk factors
      should be addressed in health education and promotion for the late consultation.

PMID- 24725621
TI  - The efficacy, safety, and pharmacokinetics of biapenem administered thrice daily
      for the treatment of pneumonia in the elderly.
AB  - Biapenem has been widely used to treat bacterial pneumonia; however, there is
      little information concerning its efficacy and safety in elderly patients. Based
      on pharmacokinetic-pharmacodynamic theory, administration of biapenem thrice
      rather than twice daily would be expected to be more effective because of longer
      time above the minimum inhibitory concentration. In this study, we aimed to
      evaluate the efficacy, safety, and pharmacokinetics of biapenem (300 mg)
      administered thrice daily in pneumonic patients aged 65 years or older. Biapenem
      was effective in 22 of 25 patients, as assessed by the improvement in clinical
      symptoms and/or the eradication of the causative organisms, and caused no serious
      adverse events. The pharmacokinetic profile was established based on simulations
      using a modeling program. Among 17 patients whose causative organisms were
      detected, time above the minimum inhibitory concentration was estimated to be
      100% in 16 patients, all of whom showed clinical improvement. The results of this
      study confirmed the efficacy and safety of 300 mg of biapenem administered thrice
      daily for the treatment of pneumonia in elderly patients.

PMID- 24725623
TI  - Unilateral morning glory optic disc anomaly in a case with Down syndrome.
AB  - BACKGROUND: This case is unique because it is the first reported case of Down
      syndrome with morning glory optic disc anomaly in literature. CASE PRESENTATION:
      A 15-year-old girl with features of Down syndrome presented to the Clinic of
      Ophthalmology for a regular ophthalmologic examination. Her best corrected visual
      acuity was 20/50 in the right eye and 20/20 in the left eye. The fundus
      examination revealed findings compatible with unilateral morning glory optic disc
      anomaly in the right eye. The patient underwent a complete ophthalmologic and
      systemic evaluation to explore possible associated findings. CONCLUSION: This
      case report emphasizes the importance of ophthalmic screening-examinations in
      Down children to rule out any vision relevant pathology.

PMID- 24725624
TI  - Which language declines more? longitudinal versus cross-sectional decline of
      picture naming in bilinguals with Alzheimer's disease.
AB  - In this study, we investigated dual-language decline in non-balanced bilinguals
      with probable Alzheimer's disease (AD) both longitudinally and cross-sectionally.
      We examined patients' naming accuracy on the Boston Naming Test (BNT: Kaplan et
      al., 1983) over three testing sessions (longitudinal analysis) and compared their
      performance to that of matched controls (cross-sectional analysis). We found
      different longitudinal and cross-sectional patterns of decline: Longitudinally,
      the non-dominant language seemed to decline more steeply than the dominant
      language, but, cross-sectionally, differences between patients and controls were
      larger for the dominant than for the non-dominant language, especially at the
      initial testing session. This differential pattern of results for cross-sectional
      versus longitudinal decline was supported by correlations between decline
      measures and BNT item characteristics. Further studies will be needed to better
      characterize the nature of linguistic decline in bilinguals with AD; however,
      these results suggest that representational robustness of individual lexical
      representations, rather than language membership, might determine the time course
      of decline for naming in bilinguals with AD.

PMID- 24725625
TI  - New developmental evidence supports a homeotic frameshift of digit identity in
      the evolution of the bird wing.
AB  - BACKGROUND: The homology of the digits in the bird wing is a high-profile
      controversy in developmental and evolutionary biology. The embryonic position of
      the digits cartilages with respect to the primary axis (ulnare and ulna)
      corresponds to 2, 3, 4, but comparative-evolutionary morphology supports 1, 2, 3.
      A homeotic frameshift of digit identity in evolution could explain how cells in
      embryonic positions 2, 3, 4 began developing morphologies 1, 2, 3. Another
      alternative is that no re-patterning of cell fates occurred, and the primary axis
      shifted its position by some other mechanism. In the wing, only the anterior
      digit lacks expression of HoxD10 and HoxD12, resembling digit 1 of other limbs,
      as predicted by 1, 2, 3. However, upon loss of digit 1 in evolution, the most
      anterior digit 2 could have lost their expression, deceitfully resembling a digit
      1. To test this notion, we observed HoxD10 and HoxD12 in a limb where digit 2 is
      the most anterior digit: The rabbit foot. We also explored whether early
      inhibition of Shh signalling in the embryonic wing bud induces an experimental
      homeotic frameshift, or an experimental axis shift. We tested these hypotheses
      using DiI injections to study the fate of cells in these experimental wings.
      RESULTS: We found strong transcription of HoxD10 and HoxD12 was present in the
      most anterior digit 2 of the rabbit foot. Thus, we found no evidence to question
      the use of HoxD expression as support for 1, 2, 3. When Shh signalling in early
      wing buds is inhibited, our fate maps demonstrate that an experimental homeotic
      frameshift is induced. CONCLUSION: Along with comparative morphology, HoxD
      expression provides strong support for 1, 2, 3 identity of wing digits. As an
      explanation for the offset 2, 3, 4 embryological position, the homeotic
      frameshift hypothesis is consistent with known mechanisms of limb development,
      and further proven to be experimentally possible. In contrast, the underlying
      mechanisms and experimental plausibility of an axis shift remain unclear.

PMID- 24725626
TI  - Late-life schizophrenia: remission, recovery, resilience.

PMID- 24725627
TI  - Older adults with prejudicial attitudes report higher post-traumatic stress
      disorder symptoms following exposure to African refugees' violence.

PMID- 24725628
TI  - Leisure activities as dementia care strategy.

PMID- 24725629
TI  - Response to Park's letter to the editor.

PMID- 24725630
TI  - [Predicting individual risk of high healthcare cost to identify complex chronic
      patients].
AB  - OBJECTIVE: To develop a predictive model for the risk of high consumption of
      healthcare resources, and assess the ability of the model to identify complex
      chronic patients. METHODS: A cross-sectional study was performed within a
      healthcare management organization by using individual data from 2 consecutive
      years (88,795 people). The dependent variable consisted of healthcare costs above
      the 95th percentile (P95), including all services provided by the organization
      and pharmaceutical consumption outside of the institution. The predictive
      variables were age, sex, morbidity-based on clinical risk groups (CRG)-and
      selected data from previous utilization (use of hospitalization, use of high-cost
      drugs in ambulatory care, pharmaceutical expenditure). A univariate descriptive
      analysis was performed. We constructed a logistic regression model with a 95%
      confidence level and analyzed sensitivity, specificity, positive predictive
      values (PPV), and the area under the ROC curve (AUC). RESULTS: Individuals
      incurring costs >P95 accumulated 44% of total healthcare costs and were
      concentrated in ACRG3 (aggregated CRG level 3) categories related to multiple
      chronic diseases. All variables were statistically significant except for sex.
      The model had a sensitivity of 48.4% (CI: 46.9%-49.8%), specificity of 97.2% (CI:
      97.0%-97.3%), PPV of 46.5% (CI: 45.0%-47.9%), and an AUC of 0.897 (CI: 0.892 to
      0.902). CONCLUSIONS: High consumption of healthcare resources is associated with
      complex chronic morbidity. A model based on age, morbidity, and prior utilization
      is able to predict high-cost risk and identify a target population requiring
      proactive care.

PMID- 24725631
TI  - Heavy drinking and alcohol-related injuries in college students.
AB  - OBJECTIVE: The main objective of this study is to evaluate the effect of heavy
      drinking on alcohol-related injuries. MATERIAL AND METHODS: We carried out an
      open cohort study among university students in Spain (n=1,382). Heavy drinking
      and alcohol-related injuries were measured by administrating AUDIT questionnaires
      to every participant at the ages of 18, 20, 22 and 24. For data analysis we used
      a Multilevel Logistic Regression for repeated measures adjusting for consumption
      of alcohol and cannabis. RESULTS: The response rate at the beginning of the study
      was 99.6% (1,369 students). The incidence rate of alcohol-related injuries was
      3.2 per 100 students year. After adjusting for alcohol consumption and cannabis
      use, the multivariate model revealed that a high frequency of heavy drinking was
      a risk factor for alcohol-related injuries (Odds Ratio=3.89 [95%CI: 2.16 -
      6.99]). The proportion of alcohol-related injuries in exposed subjects
      attributable to heavy drinking was 59.78% [95%CI: 32.75 - 75.94] while the
      population attributable fraction was 45.48% [95%CI: 24.91 - 57.77]. CONCLUSION:
      We can conclude that heavy drinking leads to an increase of alcohol-related
      injuries. This shows a new dimension on the consequences of this public concern
      already related with a variety of health and social problems. Furthermore, our
      results allow us to suggest that about half of alcohol-related injuries could be
      avoided by removing this consumption pattern.

PMID- 24725632
TI  - Symptom dimensional approach and BDNF in unmedicated obsessive-compulsive
      patients: an exploratory study.
AB  - IntroductionThe dimensional approach of the obsessive-compulsive symptoms may
      help to find more homogeneous groups of patients. The brain derived neurotrophic
      factor (BDNF) may help to identify neurobiological differences between obsessive
      compulsive symptom dimensions. METHODS: We compared serum BDNF (pg/MUg) levels of
      25 unmedicated patients meeting Diagnostic and Statistical Manual of Mental
      Disorders, Fourth Edition criteria for obsessivecompulsive disorder (OCD) and 25
      controls, using the Dimensional Yale-Brown Obsessive-Compulsive Scale, the Yale
      Brown Obsessive-Compulsive Scale and the Beck's Anxiety and Depression
      Inventories. RESULTS: There were no sociodemographic differences between the
      groups. The standard error of mean serum BDNF levels were reduced in unmedicated
      OCD patients (0.47+0.038) when compared to healthy controls (0.75+0.060)
      (P<.001). The patients with the presence of sex/religion obsessive-compulsive
      symptoms (OCS) dimension (P=.002), with chronic course of OCS (P=.022) and the
      presence of lifetime major depression (P=.016) and social anxiety (P=.030)
      presented higher levels of BDNF than OCD patients without those features. The
      severity of aggression (P=.039) and sex/religion (P<.001) OCS dimension presented
      direct (moderate and strong, respectively) correlation with serum BDNF levels in
      this sample. Serum BDNF levels were decreased in OCD patients when compared to
      healthy controls.Discussion/ConclusionSexual and religious content of symptoms
      and aggression and sex/religion dimensions severity should be better explored,
      since these specific OCS dimensions could be based on neurocircuits diverse from
      those of the other OCS dimensions.

PMID- 24725633
TI  - Clinical and pharmacologic perspectives on the treatment of major depressive
      disorder.
AB  - Major depressive disorder (MDD) is commonly encountered in clinical practice but
      is often underdiagnosed and undertreated, in part because many patients present
      only with vague somatic complaints instead of typical depressed symptomatology.
      Once diagnosed, patients with MDD can be treated with pharmacologic and/or
      nonpharmacologic therapies, but it is difficult to predict how or whether an
      individual will respond. Studies have shown that the majority of depressed
      patients fail to remit with initial therapy and, even if remission is achieved,
      many patients will relapse. While the management of patients with MDD presents
      challenges, data indicate that the achievement and maintenance of remission can
      be improved by frequent follow-ups with a clinician who can provide
      individualized education/support and appropriate referral to other healthcare
      specialists. Novel pharmacotherapies that are formulated for oncedaily dosing
      with improved safety profiles can improve adherence to treatment and reduce the
      morbidity and mortality associated with MDD. 

PMID- 24725634
TI  - Hostility, Impulsivity, and Behavior Inhibition Among Women with PMDD.
AB  - IntroductionThis study aimed to compare hostility, impulsivity, and behavior
      inhibition between women with and without premenstrual dysphoric disorder (PMDD)
      during both luteal and follicular phases and to examine whether these variables
      contribute to irritability and daily functional impairment of PMDD. METHODS: PMDD
      was screened via the Premenstrual Symptoms Screening Tool. A diagnosis of PMDD
      was confirmed by psychiatric interviewing without 2-month prospective
      confirmation. Sixty women in the PMDD group and 60 women in the control group
      completed the Chinese Version of the Buss-Durkee Hostility Inventory-Short Form,
      Dickman's Impulsivity Inventory, and the Behavior Inhibition System Scale during
      the luteal and follicular phases. RESULTS: We found that the PMDD group had
      significantly higher levels of hostility, dysfunctional impulsivity, and
      behavioral inhibition than the control group in both luteal and follicular
      phases. The PMDD group also had more premenstrual aggravation on total hostility,
      hostility affect, and suppressive hostility than the control group. Higher
      hostility, dysfunctional impulsivity, and behavior inhibition were associated
      with more severe irritability and functional impairment of
      PMDD.DiscussionHostility, impulsivity, and behavior inhibition might contribute
      to irritability and functional impairment in women with PMDD. CONCLUSION:
      Assessment and interventions based on these factors should be provided for women
      with PMDD, especially in the luteal phase.

PMID- 24725635
TI  - The artificial neural network approach based on uniform design to optimize the
      fed-batch fermentation condition: application to the production of iturin A.
AB  - BACKGROUND: Iturin A is a potential lipopeptide antibiotic produced by Bacillus
      subtilis. Optimization of iturin A yield by adding various concentrations of
      asparagine (Asn), glutamic acid (Glu) and proline (Pro) during the fed-batch
      fermentation process was studied using an artificial neural network-genetic
      algorithm (ANN-GA) and uniform design (UD). Here, ANN-GA based on the UD data was
      used for the first time to analyze the fed-batch fermentation process. The ANN-GA
      and UD methodologies were compared based on their fitting ability, prediction and
      generalization capacity and sensitivity analysis. RESULTS: The ANN model based on
      the UD data performed well on minimal statistical designed experimental number
      and the optimum iturin A yield was 13364.5 +/- 271.3 U/mL compared with a yield
      of 9929.0 +/- 280.9 U/mL for the control (batch fermentation without adding the
      amino acids). The root-mean-square-error for the ANN model with the training set
      and test set was 4.84 and 273.58 respectively, which was more than two times
      better than that for the UD model (32.21 and 483.12). The correlation coefficient
      for the ANN model with training and test sets was 100% and 92.62%, respectively
      (compared with 99.86% and 78.58% for UD). The error% for ANN with the training
      and test sets was 0.093 and 2.19 respectively (compared with 0.26 and 4.15 for
      UD). The sensitivity analysis of both methods showed the comparable results. The
      predictive error of the optimal iturin A yield for ANN-GA and UD was 0.8% and
      2.17%, respectively. CONCLUSIONS: The satisfactory fitting and predicting
      accuracy of ANN indicated that ANN worked well with the UD data. Through ANN-GA,
      the iturin A yield was significantly increased by 34.6%. The fitness, prediction,
      and generalization capacities of the ANN model were better than those of the UD
      model. Further, although UD could get the insight information between variables
      directly, ANN was also demonstrated to be efficient in the sensitivity analysis.
      The results of these comparisons indicated that ANN could be a better alternative
      way for fermentation optimization with limited number of experiments.

PMID- 24725636
TI  - Clinical-radiological, histological and genetic analyses in a lung transplant
      recipient with Mounier-Kuhn syndrome and end-stage chronic obstructive pulmonary
      disease.
AB  - BACKGROUND AND AIMS: The Mounier-Kuhn syndrome (MKS) is a rare disease
      characterized by a pathological dilation of the trachea and the bronchial system.
      The etiology of the disorder remains elusive, but genetic alterations and
      degradation of elastic fibers are thought to be involved in the pathogenesis. No
      causative treatment is available although transplantation is an option for end
      stage disease. Here, we describe a patient suffering from MKS who received a
      double lung transplant at our department. METHODS: Since a familial clustering of
      MKS is discussed in the literature, we performed a chromosomal analysis and an
      array-comparative genomic hybridization (CGH) to search for genetic
      abnormalities. At the time of transplantation, we collected samples from the
      bronchi and performed hematoxylin and eosin (HE), Elastic von-Gieson (EVG) and
      immunohistochemical stains of the explanted MKS bronchus, a control bronchus and
      of the inflammatory infiltrates. Specimens of main bronchi from the donor lung
      harvested for transplant served as control. Bronchial smears were taken from both
      main bronchi of the recipient for microbiological cultures. RESULTS: No genetic
      alterations could be found in chromosomal analysis and in array-CGH. Histological
      analysis revealed a strong reduction of elastic fibers in the submucosal
      connective tissue and a diffuse inflammatory infiltrate, mainly comprised of CD4+
      cells. In addition, immunohistochemistry showed increased matrix
      metalloproteinases (MMPs) protein expression of MMP-1, 2, 3 and 9. CONCLUSIONS:
      Based on our findings, we hypothesize that MKS is a chronic inflammatory disease
      characterized by an MMP-mediated degradation of submucosal elastic fibers.

PMID- 24725637
TI  - Emergency arterio-venous loop for free-flap defect reconstruction of the lower
      thigh with a post-irradiated and heavily infected wound.
AB  - Although being a safe and standardised procedure, free-flap reconstruction can be
      harmful if unpredictable situations occur intraoperatively. The case presented
      reveals a situation in which an unscheduled interdisciplinary approach allowed to
      complete our reconstructive aim. An extensive defect at the thigh was planned for
      reconstruction by means of a free rectus abdominis flap. As the distant part of
      the flap showed a compromised perfusion during operation and had to be partially
      discarded, our colleagues from the vascular surgery department created an arterio
      venous loop for anastomosis. This allowed a more distant positioning of the flap
      and ensured a complete defect reconstruction. 

PMID- 24725638
TI  - Impact of increasing Ultraviolet-B (UV-B) radiation on photosynthetic processes.
AB  - Increased UV-B radiation on the earth's surface due to depletion of stratospheric
      ozone layer is one of the changes of current climate-change pattern. The
      deleterious effects of UV-B radiation on photosynthesis and photosynthetic
      productivity of plants are reviewed. Perusal of relevant literature reveals that
      UV-B radiation inflicts damage to the photosynthetic apparatus of green plants at
      multiple sites. The sites of damage include oxygen evolving complex, D1/D2
      reaction center proteins and other components on the donor and acceptor sides of
      PS II. The radiation inactivates light harvesting complex II and alters gene
      expression for synthesis of PS II reaction center proteins. Mn cluster of water
      oxidation complex is the most important primary target of UV-B stress whereas D1
      and D2 proteins, quinone molecules and cytochrome b are the subsequent targets of
      UV-B. In addition, photosynthetic carbon reduction is also sensitive to UV-B
      radiation which has a direct effect on the activity and content of Rubisco. Some
      indirect effects of UV-B radiation include changes in photosynthetic pigments,
      stomatal conductance and leaf and canopy morphology. The failure of protective
      mechanisms makes PS II further vulnerable to the UV-B radiation. Reactive oxygen
      species are involved in UV-B induced responses in plants, both as signaling and
      damaging agents. Exclusion of ambient UV components under field conditions
      results in the enhancement of the rate of photosynthesis, PS II efficiency and
      subsequently increases the biomass accumulation and crop yield. It is concluded
      that predicted future increase in UV-B irradiation will have significant impact
      on the photosynthetic efficiency and the productivity of higher plants. 

PMID- 24725639
TI  - Quality control of Photosystem II: the molecular basis for the action of FtsH
      protease and the dynamics of the thylakoid membranes.
AB  - The reaction center-binding D1 protein of Photosystem II is damaged by excessive
      light, which leads to photoinhibition of Photosystem II. The damaged D1 protein
      is removed immediately by specific proteases, and a metalloprotease FtsH located
      in the thylakoid membranes is involved in the proteolytic process. According to
      recent studies on the distribution and organization of the protein
      complexes/supercomplexes in the thylakoid membranes, the grana of higher plant
      chloroplasts are crowded with Photosystem II complexes and light-harvesting
      complexes. For the repair of the photodamaged D1 protein, the majority of the
      active hexameric FtsH proteases should be localized in close proximity to the
      Photosystem II complexes. The unstacking of the grana may increase the area of
      the grana margin and facilitate easier access of the FtsH proteases to the
      damaged D1 protein. These results suggest that the structural changes of the
      thylakoid membranes by light stress increase the mobility of the membrane
      proteins and support the quality control of Photosystem II. 

PMID- 24725640
TI  - At high risk for early withdrawal: using a cumulative risk model to increase
      retention in the first year of the TEDDY study.

PMID- 24725641
TI  - A novel approach used outcome distribution curves to estimate the population
      level impact of a public health intervention.
AB  - OBJECTIVES: To provide an analytical framework within which public health
      interventions can be evaluated, present its mathematical proof, and demonstrate
      its use using real trial data. STUDY DESIGN AND SETTING: This article describes a
      method to assess population-level effects by describing change using the
      distribution curve. The area between the two overlapping distribution curves at
      baseline and follow-up represents the impact of the intervention, that is, the
      proportion of the target population that benefited from the intervention.
      RESULTS: Using trial data from a parenting program, empirical proof of the idea
      is demonstrated on a measure of behavioral problems in 355 preschoolers using the
      Gaussian distribution curve. The intervention group had a 12% [9%-17%] health
      gain, whereas the control group had 3% [1%-7%]. In addition, for the subgroup of
      parents with lower education, the intervention produced a 15% [6%-25%]
      improvement, whereas for the group of parents with higher education the net
      health gain was 6% [4%-16%]. CONCLUSION: It is possible to calculate the impact
      of public health interventions by using the distribution curve of a variable,
      which requires knowing the distribution function. The method can be used to
      assess the differential impact of population interventions and their potential to
      improve health inequities.

PMID- 24725642
TI  - Citation networks of related trials are often disconnected: implications for
      bidirectional citation searches.
AB  - BACKGROUND AND OBJECTIVES: Reports of randomized controlled trials (RCTs) should
      set findings within the context of previous research. The resulting network of
      citations would also provide an alternative search method for clinicians,
      researchers, and systematic reviewers seeking to base decisions on all available
      evidence. We sought to determine the connectedness of citation networks of RCTs
      by examining direct (referenced trials) and indirect (through references of
      referenced trials, etc) citation of trials to one another. METHODS: Meta-analyses
      were used to create citation networks of RCTs addressing the same clinical
      questions. The primary measure was the proportion of networks where following
      citation links between RCTs identifies the complete set of RCTs, forming a single
      connected citation group. Other measures included the number of disconnected
      groups (islands) within each network, the number of citations in the network
      relative to the maximum possible, and the maximum number of links in the path
      between two connected trials (a measure of indirectness of citations). RESULTS:
      We included 259 meta-analyses with a total of 2,413 and a median of seven RCTs
      each. For 46% (118 of 259) of networks, the RCTs formed a single connected
      citation group-one island. For the other 54% of networks, where at least one RCT
      group was not cited by others, 39% had two citation islands and 4% (10 of 257)
      had 10 or more islands. On average, the citation networks had 38% of the possible
      citations to other trials (if each trial had cited all earlier trials). The
      number of citation islands and the maximum number of citation links increased
      with increasing numbers of trials in the network. CONCLUSION: Available evidence
      to answer a clinical question may be identified by using network citations
      created with a small initial corpus of eligible trials. However, the number of
      islands means that citation networks cannot be relied on for evidence retrieval.

PMID- 24725643
TI  - Applying Grading of Recommendations Assessment, Development and Evaluation
      (GRADE) to diagnostic tests was challenging but doable.
AB  - OBJECTIVES: The Grading of Recommendations Assessment, Development and Evaluation
      (GRADE) Working Group developed an approach to assess the quality of evidence of
      diagnostic tests. Its use in Cochrane diagnostic test accuracy reviews is new. We
      applied this approach to three Cochrane reviews with the aim of better
      understanding the application of the GRADE criteria to such reviews. STUDY DESIGN
      AND SETTING: We selected reviews to achieve clinical and methodological
      diversities. At least three assessors independently assessed each review
      according to the GRADE criteria of risk of bias, indirectness, imprecision,
      inconsistency, and publication bias. Two teleconferences were held to share
      experiences. RESULTS: For the interpretation of the GRADE criteria, it made a
      difference whether assessors looked at the evidence from a patient-important
      outcome perspective or from a test accuracy standpoint. GRADE criteria such as
      inconsistency, imprecision, and publication bias were challenging to apply as was
      the assessment of comparative test accuracy reviews. CONCLUSION: The perspective
      from which evidence is graded can influence judgments about quality. Guidance on
      application of GRADE to comparative test reviews and on the GRADE criteria of
      inconsistency, imprecision, and publication bias will facilitate the
      operationalization of GRADE for diagnostics.

PMID- 24725644
TI  - Inclusion of nonrandomized studies in Cochrane systematic reviews was found to be
      in need of improvement.
AB  - OBJECTIVES: Nonrandomized studies (NRSs) are considered to provide less reliable
      evidence for intervention effects. However, these are included in Cochrane
      reviews, despite discouragement. There has been no evaluation of when and how
      these designs are used. Therefore, we conducted an overview of current practice.
      STUDY DESIGN AND SETTING: We included all Cochrane reviews that considered NRS,
      conducting inclusions and data extraction in duplicate. RESULTS: Of the included
      202 reviews, 114 (56%) did not cite a reason for including NRS. The reasons were
      divided into two major categories: NRS were included because randomized
      controlled trials (RCTs) are wanted (N = 81, 92%) but not feasible, lacking, or
      insufficient alone or because RCTs are not needed (N = 7, 8%). A range of designs
      were included with controlled before-after studies as the most common. Most
      interventions were nonpharmaceutical and the settings nonmedical. For risk of
      bias assessment, Cochrane Effective Practice and Organisation of Care Group's
      checklists were used by most reviewers (38%), whereas others used a variety of
      checklists and self-constructed tools. CONCLUSION: Most Cochrane reviews do not
      justify including NRS. When they do, most are not in line with Cochrane
      recommendations. Risk of bias assessment varies across reviews and needs
      improvement.

PMID- 24725645
TI  - Helfrich's concept of intrinsic force and its molecular origin in bilayers and
      monolayers.
AB  - Bilayers and monolayers are excellent models of biological membranes. The
      constituents of the biological membranes such as lipids, cholesterols and
      proteins are chiral. Chiral molecules are abundant in nature (protein, nucleic
      acid and lipid). It is obvious that relationship between chirality and morphology
      (as well as function) of biological membrane is of interest for its fundamental
      importance and has technological implication regarding various membrane
      functions. The recent years have witnessed that a number of experimental studies
      in biomimetic systems have shown fascinating morphologies where chirality of the
      constituent molecule has decisive influence. Significant progress is made towards
      the understanding of these systems from the theoretical and computational
      studies. Helfrich's concept of intrinsic force arising from chirality is a
      milestone in understanding the biomimetic system such as bilayer and the related
      concepts, further progresses in molecular understanding made in recent years and
      experimental studies revealing the influence of chirality on morphology are the
      focus of the present review. Helfrich's concept of intrinsic force arising due to
      chirality is useful in understanding two-dimensional bilayers and one-dimensional
      monolayers and related mimetic systems. Various experimental techniques are used,
      which can probe the molecular architecture of these mimetic systems at different
      length scales and both macroscopic (thermodynamic) as well as microscopic
      (molecular) theories are developed. These studies are aimed to understand the
      role of chirality in the molecular interaction when the corresponding molecule is
      present in an aggregate. When one looks into the variety of morphologies
      exhibited by three-dimensional bilayer and two-dimensional monolayer, the later
      types of systems are more exotic in the sense that they show more diversity and
      interesting chiral discrimination. Helfrich's concept of intrinsic force may be
      considered useful in both cases. The intrinsic force due to chirality is the
      decisive factor in determining morphology which is explained by molecular
      approaches. Finally, biological and technological implications of such
      morphological variations are briefly mentioned. 

PMID- 24725646
TI  - Properties of Langmuir and solid supported lipid films with sphingomyelin.
AB  - Biological cell membranes play a crucial role in various biological processes and
      their functionality to some extent is determined by the hydrophilic/hydrophobic
      balance. A significant progress in understanding the membrane structure was the
      discovery of laterally segregated lipid domains, called the lipid rafts. These
      raft domains are of ordered lamellar liquid-crystalline phase, while rest of the
      membrane exists in a relatively disordered lamellar liquid-crystalline phase.
      Moreover, the chemical constitution of the lipid rafts consists of a higher
      content (up to 50%) of cholesterol (Chol) and sphingomyelin (SM). Sphingomyelin
      also plays a significant role in the red cells of blood and nerves, in some
      diseases, as a precursor to ceramides, and other sphingolipid metabolites. In
      this paper properties of Langmuir and solid supported mixed lipid films of
      DPPC/SM, DOPC/SM, and Chol/SM are described. Special attention has been paid to
      wetting properties (hydrophobic/hydrophilic balance) of these films transferred
      onto a hydrophilic glass surface. To our knowledge such results have not yet been
      published in the literature. The properties were determined via contact angle
      measurements and then calculation of the films' apparent surface free energy. The
      films' wettability and their apparent surface free energy strongly depend on
      their composition. The energy is affected by both the structure of hydrocarbon
      chains of glycerophospholipids (DPPC and DOPC) and their interactions with SM.
      Properties of mixed Chol/SM monolayer depend also on the film stoichiometry. At a
      low Chol content (XChol=0.25) the interactions between SM and Chol are strong and
      hence the formation of binary complex is possible. This is accompanied by a
      decrease in the film surface free energy in comparison to that of pure SM
      monolayer, contrary to a higher Chol content where the monolayer energy
      increases. This suggests that cholesterol is excluded from the membrane thus
      increasing the film hydrophilicity. These results are consistent with the
      literature data and somehow confirm the hypothesis of lipid raft formation. The
      roughness of the investigated monolayer surfaces was also determined using
      optical profilometry. The roughness parameters of the DPPC, SM, and mixed DPPC/SM
      generally correlate with the changes of their apparent surface free energy, i.e.
      with the decreasing roughness the apparent surface free energy also decreases.
      However, this is not the case for mixed DOPC/SM monolayers. Although the
      roughness increases with SM content the apparent surface free energy decreases.
      Therefore some other factors, like the presence of unsaturated bonds in the DOPC
      molecule, influence the film phase state and the energy too. More experiments are
      needed to explain this hypothesis. 

PMID- 24725647
TI  - Onabotulinum toxin A for the treatment of sialorrhea in familial dysautonomia.
AB  - Familial dysautonomia is a rare disease affecting the nervous system. Symptoms
      include speech and movement problems, anterior sialorrhea (drooling) due to
      hypersalivation as a consequence of poor oropharyngeal coordination; dysphagia
      and aspiration pneumonia secondary to recurrent posterior sialorrhea. The
      treatment for sialorrhea in this population is very challenging. Traditional
      drugs carry a number of side-effects that are difficult to control in this
      disease. We report the first documented case series of 3 patients with this
      condition that successfully responded to Onabotulinum toxin A injection into
      their salivary glands. This is an innovative, safe method for drooling control in
      this population. 

PMID- 24725648
TI  - The nasogastric tube syndrome in infants.
AB  - This series of three patients is the first description of the presentation,
      clinical course, and endoscopic findings of nasogastric tube-related airway
      distress, or nasogastric tube syndrome, in infants. We identify key differences
      in disease features from those described in adults, based on our literature
      review. Specifically, infant nasogastric tube syndrome presented as significant
      respiratory distress and postcricoid inflammation without vocal fold immobility.
      Symptoms resolved more quickly (mean+/-SD, 2+/-1 days) than reported in adults.
      We suggest that nasogastric tube syndrome should be considered in infants with
      otherwise unexplained respiratory distress, even in the absence of impaired vocal
      fold mobility. 

PMID- 24725649
TI  - Response to the Letter to the Editor regarding "A questionnaire-based study on
      parental satisfaction with a universal newborn hearing screening program in Kuala
      Lumpur, Malaysia".

PMID- 24725650
TI  - Shifting paradigms of nontuberculous mycobacteria in cystic fibrosis.
AB  - Important paradigms of pulmonary disease with nontuberculous mycobacteria (NTM)
      are currently shifting based on an increasing attention within the field of
      cystic fibrosis (CF). These shifts are likely to benefit the management of all
      patients with pulmonary NTM, regardless of underlying pathology. Currently
      several key areas are being revised: The first outbreak of human NTM transmission
      has been proven and new evidence of biofilm growth in vivo has been demonstrated.
      A better understanding of the clinical impact of NTM infection has led to
      increased diagnostic vigilance and new recommendations for lung transplantation
      are under way. While recent changes have reinvigorated the interest in NTM
      disease, the challenge remains, whether such advances can be successfully
      translated into improved management and care. 

PMID- 24725651
TI  - Metacognitive functioning predicts positive and negative symptoms over 12 months
      in first episode psychosis.
AB  - The negative symptoms of schizophrenia are a major source of impairment and
      distress but both pharmacological and psychological treatment options provide
      only modest benefit. Developing more effective psychological treatments for
      negative symptoms will require a more sophisticated understanding of the
      psychological processes that are implicated in their development and maintenance.
      We extended previous work by demonstrating that metacognitive functioning is
      related to negative symptom expression across the first 12 months of first
      episode psychosis (FEP). Previous studies in this area have either been cross
      sectional or have used much older participants with long-standing symptoms. In
      this study, forty-five FEP participants were assessed three times over 12 months
      and provided data on PANSS rated symptoms, premorbid adjustment, metacognitive
      functioning, and DUP. Step-wise linear regression showed that adding
      metacognition scores to known predictors of negative symptoms (baseline symptom
      severity, gender, DUP, and premorbid academic and social adjustment) accounted
      for 62% of the variance in PANSS negative symptom scores at six months and 38% at
      12 months. The same predictors also explained 47% of the variance in positive
      symptoms at both six and 12 months. However, exploration of the simple
      correlations between PANSS symptom scores and metacognition suggests a stronger
      univariate relationship between metacognition and negative symptoms. Overall, the
      results indicate that problems with mental state processing may be important
      determinants of negative symptom expression from the very early stages of
      psychosis. These results provide further evidence that metacognitive functioning
      is a potentially relevant target for psychological interventions. 

PMID- 24725652
TI  - Methylenetetrahydrofolate reductase gene variants and antipsychotic-induced
      weight gain and metabolic disturbances.
AB  - Weight gain and metabolic disturbances represent serious side-effects in
      antipsychotic (AP) treatment, particularly with clozapine and olanzapine. The
      methylenetetrahydrofolate reductase (MTHFR) gene is a key determinant in the
      folate metabolism and previous studies reported a significant effect on AP
      induced weight gain and related metabolic abnormalities. Thus, we investigated
      MTHFR gene variants and changes in several important metabolic parameters in AP
      treated patients. In this study, two functional MTHFR polymorphisms, rs1801133
      (C677T) and rs1801131 (A1298C), were investigated for changes in weight and
      metabolic parameters. Genotypic associations were evaluated in a large population
      (n = 347 including 66 first episode psychosis, FEP patients) treated mostly with
      clozapine and olanzapine. We did not detect any genotypic association with weight
      changes (p > 0.05) in our total sample and in the sample refined for ancestry and
      medication. In our allelic analyses, we observed a trend for the 677-C allele to
      be associated with weight gain in the total sample (p = 0.03). This effect
      appeared to be driven by the FEP patients where those carrying the C-allele
      gained, on average, twice as much weight. Exploratory analyses revealed a
      significant association between the C677T and the A1298C polymorphism with HDL
      cholesterol serum levels in patients (p = 0.031). Overall we did not detect a
      major effect of two functional MTHFR gene variants and AP-induced weight gain.
      However, our findings suggest an effect of the C677T polymorphism in FEP patients
      and changes in weight and cholesterol levels. Further investigations in a larger
      sample are required.

PMID- 24725653
TI  - A paradox in suicide statistics in estimating specificity of tests for suicide -
      reply to Mushquash and co-workers and Culver.

PMID- 24725654
TI  - Pylorus preserving loop duodeno-enterostomy with sleeve gastrectomy - preliminary
      results.
AB  - BACKGROUND: Bariatric operations mostly combine a restrictive gastric component
      with a rerouting of the intestinal passage. The pylorus can thereby be
      alternatively preserved or excluded. With the aim of performing a "pylorus
      preserving gastric bypass", we present early results of a proximal postpyloric
      loop duodeno-jejunostomy associated with a sleeve gastrectomy (LSG) compared to
      results of a parallel, but distal LSG with a loop duodeno-ileostomy as a two-step
      procedure. METHODS: 16 patients underwent either a two-step LSG with a distal
      loop duodeno-ileostomy (DIOS) as revisional bariatric surgery or a combined
      single step operation with a proximal duodeno-jejunostomy (DJOS). Total small
      intestinal length was determined to account for inter-individual differences.
      RESULTS: Mean operative time for the second-step of the DIOS operation was 121
      min and 147 min for the combined DJOS operation. The overall intestinal length
      was 750.8 cm (range 600-900 cm) with a bypassed limb length of 235.7 cm in DJOS
      patients. The mean length of the common channel in DIOS patients measured 245.6
      cm. Overall excess weight loss (%EWL) of the two-step DIOS procedure came to
      38.31% and 49.60%, DJOS patients experienced an %EWL of 19.75% and 46.53% at 1
      and 6 months, resp. No complication related to the duodeno-enterostomy occurred.
      CONCLUSIONS: Loop duodeno-enterosomies with sleeve gastrectomy can be safely
      performed and may open new alternatives in bariatric surgery with the possibility
      for inter-individual adaptation.

PMID- 24725655
TI  - Nosocomial and ventilator-associated pneumonia in a community hospital intensive
      care unit: a retrospective review and analysis.
AB  - BACKGROUND: Nosocomial and ventilator-associated pneumonia (VAP) are causes of
      significant morbidity and mortality in hospitalized patients. We analyzed a) the
      incidence and the outcome of pneumonias caused by different pathogens in the
      intensive care unit (ICU) of a medium-sized twenty-four bed community hospital
      and b) the incidence of complications of such pneumonias requiring surgical
      intervention such as thoracotomy and decortication. RESULTS: We retrospectively
      reviewed the charts of patients diagnosed with nosocomial and ventilator
      associated pneumonia in our ICU. Their bronchoalveolar lavage (BAL) and sputum
      cultures, antibiograms, and other clinical characteristics, including
      complications and need for tracheostomy, thoracotomy and decortication were
      studied. In a span of one year (2011-12), 43 patients were diagnosed with
      nosocomial pneumonia in our ICU. The median simplified acute physiology score
      (SAPS II) was 39. One or more gram negative organisms as the causative agents
      were present in 85% of microbiologic samples. The three most prevalent gram
      negatives were Stenotrophomonas maltophilia (34%), Pseudomonas aeurginosa (40%),
      and Acinetobacter baumannii (32%). Twenty eight percent of bronchoalveolar
      samples contained Staphylococcus aureus. Eight three percent of patients required
      mechanical ventilation postoperatively and 37% underwent tracheostony. Thirty
      five percent underwent thoracotomy and decortication because of further
      complications such as empyema and non-resolving parapneumonic effusions. A.
      baumannii, Klebsiella pneumonia extended spectrum beta lactam (ESBL) and P.
      aeurginosa had the highest prevalence of multi drug resistance (MDR). Fifteen
      patients required surgical intervention. Mortality from pneumonia was 37% and
      from surgery was 2%. CONCLUSION: Nosocomial pneumonias, in particular the ones
      that were caused by gram negative drug resistant organisms and their ensuing
      complications which required thoracotomy and decortication, were the cause of
      significant morbidity in our intensive care unit. Preventative and more intensive
      and novel infection control interventions in reducing the incidence of nosocomial
      pneumonias are strongly emphasized.

PMID- 24725656
TI  - Multimodal emotion integration in bipolar disorder: an investigation of
      involuntary cross-modal influences between facial and prosodic channels.
AB  - The ability to integrate information from different sensory channels is a vital
      process that serves to facilitate perceptual decoding in times of unimodal
      ambiguity. Despite its relevance to psychosocial functioning, multimodal
      integration of emotional information across facial and prosodic modes has not
      been addressed in bipolar disorder (BD). In light of this paucity of research we
      investigated multimodal processing in a BD cohort using a focused attention
      paradigm. Fifty BD patients and 52 healthy controls completed a task assessing
      the cross-modal influence of emotional prosody on facial emotion recognition
      across congruent and incongruent facial and prosodic conditions, where attention
      was directed to the facial channel. There were no differences in multi-modal
      integration between groups at the level of accuracy, but differences were evident
      at the level of response time; emotional prosody biased facial recognition
      latencies in the control group only, where a fourfold increase in response times
      was evident between congruent and incongruent conditions relative to patients.
      The results of this study indicate that the automatic process of integrating
      multimodal information from facial and prosodic sensory channels is delayed in
      BD. Given that interpersonal communication usually occurs in real time, these
      results have implications for social functioning in the disorder.

PMID- 24725658
TI  - Hybrid learning: to blend, flip, and interact.

PMID- 24725657
TI  - Prognostic significance of heart rate turbulence parameters in patients with
      chronic heart failure.
AB  - BACKGROUND: This study is aimed to evaluate the clinical significance of heart
      rate turbulence (HRT) parameters in predicting the prognosis in patients with
      chronic heart failure (CHF). METHODS: From June 2011 to December 2012, a total of
      104 CHF patients and 30 healthy controls were enrolled in this study. We obtained
      a 24-hour Holter ECG recording to assess the HRT parameters, included turbulence
      onset (TO), turbulence slope (TS), standard deviation of N-N intervals (SDNN),
      and resting heart rate (RHR). The relationships between HRT parameters and the
      prognosis of CHF patients were determined. RESULTS: The assessment follow-up
      period lasted until January 31, 2013. The overall mortality of CHF patients was
      9.6% (10/104). Our results revealed that CHF patients had higher levels of TO
      than those of healthy subjects, but the TS levels of CHF patients were lower than
      that of the control group. CHF patients with NYHA grade IV had higher HRT1/2 rate
      than those with NYHA grade II/III. There were statistical differences in TS,
      LVEF, SDNN and RHR between the non-deteriorating group and the non-survivor
      group. Significant differences in TS among the three groups were also found.
      Furthermore, CHF patients in the non-survivor group had lower levels of TS than
      those in the deteriorating group. Correlation analyses indicated that TO
      negatively correlate with SDNN, while TS positively correlated with SDNN and left
      ventricular ejection fraction (LVEF). We also observed negative correlations
      between TS and left ventricular end-diastolic cavity dimension (LVEDD), RHR,
      homocysteine (Hcy) and C-reactive protein (CRP). Multivariate Cox regression
      analysis further confirmed that LVEF (<=30%), HRT2, SDNN and RHR were independent
      risk factors which can indicate poor prognosis in CHF patients. CONCLUSIONS: Our
      findings indicate that HRT may have good clinical predictive value in patients
      with CHF. Thus, quantifying HRT parameters could be a useful tool for predicting
      mortality in CHF patients.

PMID- 24725660
TI  - Report from the Spanish Association of Coloproctology (AECP).

PMID- 24725661
TI  - Watch and wait for rectal cancer: where are we really at?

PMID- 24725662
TI  - Report from a consensus meeting: response to chemoradiotherapy in rectal cancer -
      predictor of cure and a crucial new choice for the patient: on behalf of the
      Champalimaud 2014 Faculty for 'Rectal cancer: when NOT to operate'.

PMID- 24725667
TI  - Personalized medicine: present and future of breast cancer management.
AB  - Breast cancer is the first cause of cancer in women worldwide. Recent molecular
      analyses have shown that it is not a single disease but a mixture of several
      diseases with different biological behaviors, which should lead to treatment
      customization for each patient. Personalized medicine is based on tumor and/or
      patient molecular profiles. This new way to think oncology is currently applied
      at different stages of breast cancer management, including prognosis, prediction
      of treatment efficacy, and development of new therapies via new kinds of clinical
      trials. These trials are not only based on tumor site but also on tumor genetic
      characterization using genomic tools such as gene expression profiling, array-CGH
      or next-generation sequencing technologies. The aim of personalized medicine is
      to tailor treatment according to the specificities of a single disease in a given
      patient. In this review, we present the advances in treatment personalization
      which are currently used in daily practice as well as the technologies and
      therapies under investigation in various clinical trials. 

PMID- 24725668
TI  - Enhancement of acetoin production in Candida glabrata by in silico-aided
      metabolic engineering.
AB  - BACKGROUND: Acetoin is a promising chemical compound that can potentially serve
      as a high value-added platform for a broad range of applications. Many industrial
      biotechnological processes are moving towards the use of yeast as a platform. The
      multi-auxotrophic yeast, Candida glabrata, can accumulate a large amount of
      pyruvate, but produces only trace amounts of acetoin. Here, we attempted to
      engineer C. glabrata to redirect the carbon flux of pyruvate to increase acetoin
      production. RESULTS: Based on an in silico strategy, a synthetic, composite
      metabolic pathway involving two distinct enzymes, acetolactate synthase (ALS) and
      acetolactate decarboxylase (ALDC), was constructed, leading to the accumulation
      of acetoin in C. glabrata. Further genetic modifications were introduced to
      increase the carbon flux of the heterologous pathway, increasing the production
      of acetoin to 2.08 g/L. Additionally, nicotinic acid was employed to regulate the
      intracellular NADH level, and a higher production of acetoin (3.67 g/L) was
      obtained at the expense of 2,3-butanediol production under conditions of a lower
      NADH/NAD+ ratio. CONCLUSION: With the aid of in silico metabolic engineering and
      cofactor engineering, C. glabrata was designed and constructed to improve acetoin
      production.

PMID- 24725669
TI  - New generation of wearable goniometers for motion capture systems.
AB  - BACKGROUND: Monitoring joint angles through wearable systems enables human
      posture and gesture to be reconstructed as a support for physical rehabilitation
      both in clinics and at the patient's home. A new generation of wearable
      goniometers based on knitted piezoresistive fabric (KPF) technology is presented.
      METHODS: KPF single-and double-layer devices were designed and characterized
      under stretching and bending to work as strain sensors and goniometers. The
      theoretical working principle and the derived electromechanical model, previously
      proved for carbon elastomer sensors, were generalized to KPF. The devices were
      used to correlate angles and piezoresistive fabric behaviour, to highlight the
      differences in terms of performance between the single layer and the double layer
      sensors. A fast calibration procedure is also proposed. RESULTS: The proposed
      device was tested both in static and dynamic conditions in comparison with
      standard electrogoniometers and inertial measurement units respectively. KPF
      goniometer capabilities in angle detection were experimentally proved and a
      discussion of the device measurement errors of is provided. The paper concludes
      with an analysis of sensor accuracy and hysteresis reduction in particular
      configurations. CONCLUSIONS: Double layer KPF goniometers showed a promising
      performance in terms of angle measurements both in quasi-static and dynamic
      working mode for velocities typical of human movement. A further approach
      consisting of a combination of multiple sensors to increase accuracy via sensor
      fusion technique has been presented.

PMID- 24725670
TI  - ARDS associated with pneumonia caused by avian influenza A H7N9 virus treated
      with extracorporeal membrane oxygenation.
AB  - This is a sporadic H7N9 avian influenza case that was the first severe imported
      case in Beijing and the first case of Hebei province in China. A 61-year-old
      female who had rapidly progressive pneumonia with respiratory distress and
      bilateral exduation and consolidation changes on chest X-ray and computerized
      tomography (CT) scan that did not respond to ordinary antibiotics was diagnosed
      with influenza A (H7N9) infection in our hospital on July 19, 2013. Intravenous
      peramivir, veno-venous extracorporeal membrane oxygenation (VV-ECMO) and
      continuous veno-venous hemofiltration were given on the same day of lab diagnosis
      because of severe acute respiratory distress syndrome and acute renal failure.
      With antimicrobial therapy and other supportive treatment, clinical symptoms and
      oxygenation of the patient improved gradually. VV-ECMO was successfully removed
      on the 13th day. The testing for influenza A (H7N9) turned negative on day 16
      since the antivirus therapy. Twenty-three days after hospitalization, blood
      stream infection with multidrug-resistant Acinetobacter Baumannii occurred, which
      lead to septic shock and death. Whether or not the influenza season in north
      China, the influenza screening should be carried out as a conventional test for
      the patients who are suspected of viral pneumonia. For the patients who need
      mechanical ventilation and ECMO support, the lung protective strategy under the
      guidance of transpulmonary pressure may be helpful for recovering the lung. 

PMID- 24725671
TI  - Prediction of near-term risk of developing breast cancer using computerized
      features from bilateral mammograms.
AB  - Asymmetry of bilateral mammographic tissue density and patterns is a potentially
      strong indicator of having or developing breast abnormalities or early cancers.
      The purpose of this study is to design and test the global asymmetry features
      from bilateral mammograms to predict the near-term risk of women developing
      detectable high risk breast lesions or cancer in the next sequential screening
      mammography examination. The image dataset includes mammograms acquired from 90
      women who underwent routine screening examinations, all interpreted as negative
      and not recalled by the radiologists during the original screening procedures. A
      computerized breast cancer risk analysis scheme using four image processing
      modules, including image preprocessing, suspicious region segmentation, image
      feature extraction, and classification was designed to detect and compute image
      feature asymmetry between the left and right breasts imaged on the mammograms.
      The highest computed area under curve (AUC) is 0.754+/-0.024 when applying the
      new computerized aided diagnosis (CAD) scheme to our testing dataset. The
      positive predictive value and the negative predictive value were 0.58 and 0.80,
      respectively. 

PMID- 24725672
TI  - Real-time MRI navigated US: role in diagnosis and guided biopsy of incidental
      breast lesions and axillary lymph nodes detected on breast MRI but not on second
      look US.
AB  - OBJECTIVES: To prospectively evaluate the accuracy of real-time ultrasound
      combined with supine-MRI using volume navigation technique (RtMR-US) in diagnosis
      and biopsy of incidental breast lesions (ILSM) and axillary lymph nodes (LNSM)
      suspicious of malignancy on contrast enhanced magnetic resonance imaging (CE
      MRI). MATERIALS AND METHODS: Five hundred and seventy-seven women were examined
      using breast CE-MRI. Those with incidental breast lesions not identified after
      second-look ultrasound (US) were recruited for RtMR-US. Biopsy was performed in
      ILSM. Breast lesions were categorized with BI-RADS system and Fisher' exact test.
      Axillary lymph nodes morphology was described. To assess efficacy of RtMR-US,
      diagnostic accuracy, sensitivity, specificity, detection rate and Kappa index of
      conventional-US and RtMR-US were calculated. RESULTS: Forty-three lesions were
      detected on CE-MRI before navigation. Eighteen were carcinomas and 25 ILSM. Of
      these, 21 underwent a RtMR-US. Detection rate on RtMR-US (90.7%) was higher than
      on conventional-US (43%) (p<0.001). Agreement between both techniques was low
      (k=0.138). Twenty ILSM and 2 LNSM were biopsied. Sixty-five percent were benign
      (100% of BI-RADS3 and 56% of BI-RADS4-5). Diagnostic performance of RtMR-US
      identifying malignant nodules for overall lesions and for the subgroup of ILSM
      was respectively: sensitivity 96.3% and 100%, specificity 18.8% and 30.7%,
      positive predictive value 66.7% and 43.7%, negative predictive value 75% and
      100%. In addition RtMR-US enabled biopsy of 2 metastatic lymph nodes.
      CONCLUSIONS: Real time-US with supine-MRI using a volume navigation technique
      increases the detection of ILSM. RtMR-US may be used to detect occult breast
      carcinomas and to assess cancer extension, preventing unnecessary MRI-guided
      biopsies and sentinel lymph node biopsies. Incidental lesions BI-RADS 3 non
      detected on conventional-US are probably benign.

PMID- 24725673
TI  - Infiltration patterns in monoclonal plasma cell disorders: correlation of
      magnetic resonance imaging with matched bone marrow histology.
AB  - OBJECTIVES: To investigate how plasma cell infiltration patterns detected by MRI
      match the plasma cell distribution in bone marrow biopsy. METHODS: We assessed 50
      patients with monoclonal plasma cell disorders of all clinical stages. MRI
      infiltration pattern was compared with matched BM histology from the same
      anatomic region. RESULTS: MRI revealed a minimal (n=11, 22%), focal (n=5, 10%),
      diffuse (n=14, 28%) and mixed (n=20, 40%) infiltration pattern. Diffuse MRI
      pattern was predominant in smoldering myeloma patients whereas the MRI patterns
      with "focal component" (i.e. focal and mixed) were most common in symptomatic
      myeloma (p<0.01). In histology an interstitial (n=13, 26%), nodular (n=23, 46%)
      and packed marrow (n=14, 28%) was found respectively. All three histological
      types of infiltration were observed in patients with diffuse and mixed MRI
      patterns. Minimal MRI pattern was found in all MGUS patients and was associated
      with an interstitial BM infiltration. In two patients with minimal MRI pattern an
      extensive micro-nodular BM infiltration was found in histology. CONCLUSIONS:
      Infiltration patterns in MRI represent different histological growth patterns of
      plasma cells, but the MRI resolution is not sufficient to visualize micro-nodular
      aggregates of plasma cells.

PMID- 24725674
TI  - Multiobjective optimization on antiplatelet effects of three components
      combination by quantitative composition-activity relationship modeling and
      weighted-sum method.
AB  - Multicomponent therapeutic has become an increasingly favored strategy for
      treating complex diseases in recent years. In this study, a multiple objective
      optimization approach was proposed to design the optimal combination of three
      components for antiplatelet activity. The platelet aggregation assays induced by
      three different ways, adenosine diphosphate, arachidonic acid, and collagen, were
      applied to evaluate the in vitro antiplatelet activities of three active
      components derived from a traditional Chinese medicine. After analyzing this
      dataset by quantitative composition-activity relationship modeling, a weighted
      sum optimization method was adopted to calculate the optimal ratio between three
      components for antiplatelet effects. Further experiments validated our method and
      showed that better antiplatelet activity was exerted by the optimized combination
      than the individual component or other combinations. Our findings suggested that
      the proposed multiobjective optimization approach is a novel method for
      multicomponent drug design. 

PMID- 24725675
TI  - Influence of diet and rennet on the composition of goats' milk and cheese.
AB  - Dry matter, protein, fat, pH, mineral (Na, K, Ca and Mg) and trace elements (Fe,
      Cu, Zn and Se) concentrations were determined in samples of goats' milk and in
      fresh, semi-hard and hard cheeses to study the effect of the goats' diet and the
      type of rennet used for the cheese processing of the Palmero Protected
      Designation of Origin cheeses. Two groups of 20 Palmero goats were fed 2
      different diets: a Palmero diet (PD supplied by native forages adapted to
      subhumid areas, which had a high ratio of long fibre to concentrates (65:35), and
      an actual diet (AD), the most commonly used by goat farmers, with a low ratio of
      long fibre to concentrates (35:65). In general, the cheese samples from goats fed
      with PD had higher mean Ca, Zn, Cu and Se concentrations than the samples
      obtained from AD fed goats. The diet exhibited a greater influence on the
      chemical composition of the cheeses than the rennet used in their production.
      Applying a stepwise linear discriminant analysis a complete percentage of correct
      classifications of the three types of cheeses according to the diet of the goats
      was observed. 

PMID- 24725676
TI  - Birth after preeclamptic pregnancies: association with allergic sensitization and
      allergic rhinoconjunctivitis in late childhood; a historically matched cohort
      study.
AB  - BACKGROUND: The development of allergic sensitization and allergic disease may be
      related to factors during intrauterine life, but the role of maternal
      preeclampsia is not known.We studied if maternal preeclampsia is associated with
      long-term allergic sensitization, allergic rhinoconjunctivitis, atopic
      dermatitis, asthma and with altered lung function in late childhood. METHODS: 617
      children participated in a 1:2 matched and controlled historical cohort study;
      230 born after preeclamptic pregnancies and 387 born after normotensive
      pregnancies. Specific IgE in serum and lung function were measured at the age of
      12.8 years and questionnaires on maternal and adolescent data were completed at
      the ages of 10.8 years (girls) and 11.8 years (boys), and at 12.8 years (both
      genders). The association between birth after preeclampsia and the main outcome
      measures allergic sensitization, allergic rhinoconjunctivitis, atopic dermatitis,
      asthma and lung function in late childhood were analysed with multiple regression
      analyses, including possible confounders. RESULTS: Severe maternal preeclampsia
      was associated with high level allergic sensitization (sum of specific IgE in
      serum >= 3.9 kU/l; the 25 percentile for all children being sensitized); odds
      ratio (OR): 3.79; 95% confidence interval (CI): (1.54, 9.32); p = 0.015 and with
      allergic rhinoconjunctivitis in offspring; OR: 2.22, 95% CI: (1.19, 4.14), p =
      0.047. Preeclampsia was not associated with atopic dermatitis, asthma or altered
      lung function in late childhood. CONCLUSION: Maternal preeclampsia was associated
      with allergic sensitization and allergic rhinoconjunctivitis in offspring in late
      childhood, but not with other atopic diseases.

PMID- 24725677
TI  - Inpatient survival after gastrectomy for gastric cancer in the 21st century.
AB  - BACKGROUND: Surgical treatment for gastric cancer has evolved substantially. To
      understand how changes in patient- and hospital-level factors are associated with
      outcomes over the last decade, we examined a nationally representative sample.
      METHODS: Retrospective cross-sectional discharge data from the 2001-2010
      Nationwide Inpatient Sample were analyzed using cross tabulation and
      multivariable regression modeling. Patients with a primary diagnosis of gastric
      cancer undergoing gastrectomy as primary procedure were included. We examined
      relationships between patient- and hospital-level factors, surgery type, and
      outcomes including in-hospital mortality and length of stay (LOS). RESULTS: A
      total of 67,327 patients with gastric cancer undergoing gastrectomy nationwide
      with complete information were included. Compared with patients treated in 2001,
      patients in 2010 were younger, more likely admitted electively, treated in a
      teaching hospital, or at an urban center. There was no difference in the type of
      procedure performed over time. Factors associated with an increased risk of in
      hospital mortality included older age, male gender, and nonelective admission
      (P<0.05). In multivariable analysis, patients undergoing gastrectomy in 2010
      demonstrated 40% lower odds of in-hospital mortality (odds ratio, 0.60; P=0.008).
      Overall mean LOS was 13.9 d (standard error, 0.1) without change over time.
      Factors associated with longer LOS included procedure type, hospital location,
      nonelective admission, and comorbid disease (all P<0.05). CONCLUSIONS: The
      adjusted odds of in-hospital mortality among surgically treated patients with
      gastric cancer decreased >40% between 2001 and 2010. Further research is
      warranted to determine if these findings are due to better patient selection,
      regionalization of care, or improvement of in-hospital quality of care.

PMID- 24725679
TI  - Initial experience with same day discharge after laparoscopic appendectomy for
      nonperforated appendicitis.
AB  - BACKGROUND: Although many laparoscopic procedures are performed on an outpatient
      basis, patients who have undergone a laparoscopic appendectomy have typically
      stayed at least overnight. Recently, data in both the pediatric and adult
      literature suggest that same day discharge (SDD) for acute nonperforated
      appendicitis is safe and associated with high patient and parent satisfaction. We
      have recently begun attempting SDD for nonperforated appendicitis, and this study
      is an analysis of our initial experience. METHODS: A retrospective chart review
      of all patients who underwent laparoscopic appendectomy for nonperforated
      appendicitis at our institution from January 2012 to July 2013 was performed.
      Demographics, length of stay, hospital course, and outcomes were measured. Data
      are expressed as mean+/-standard deviation. Comparative analysis was performed
      using a t-test. RESULTS: A total of 588 laparoscopic appendectomies for
      nonperforated appendicitis were performed over an 18-mo period. Approximately 28%
      (n=128) were discharged on the day of surgery. Of the remaining patients, 12.9%
      (n=59) stayed overnight for medical reasons, 0.4% (n=2) stayed for social
      reasons, 3.9% (n=18) stayed because the operation ended late in the evening, and
      82.8% (n=381) stayed because of clinical care habits. Compared with patients who
      stayed overnight, there was no statistically significant difference in
      readmission rates (0.7% versus 1.9%, P=0.6%), follow-up before scheduled
      appointment (5.4% versus 5.4%, P=1.0), and complication rate (0.7% versus 2.6%,
      P=0.3). Patients whose operation ended later in the day had a longer hospital
      stay. We observed a trend toward more SDDs, the further we got from the
      initiation of our protocol. CONCLUSIONS: SDD is safe for children undergoing
      laparoscopic appendectomy for nonperforated appendicitis. The two main barriers
      to SDD were time of day for the operation and provider habit, both of which
      improved as more practitioners felt comfortable with the concept. SDD requires
      extensive education within the hospital system, and we have initiated an
      aggressive prospective protocol to improve the results.

PMID- 24725678
TI  - Adenoviral-mediated gene transfer of insulin-like growth factor 1 enhances wound
      healing and induces angiogenesis.
AB  - BACKGROUND: Chronic wounds are characterized by a wound healing and
      neovascularization deficit. Strategies to increase neovascularization can
      significantly improve chronic wound healing. Insulin-like growth factor (IGF)-1
      is reported to be a keratinocyte mitogen and is believed to induce angiogenesis
      via a vascular endothelial growth factor (VEGF)-dependent pathway. Using a novel
      ex vivo human dermal wound model and a diabetic-impaired wound healing murine
      model, we hypothesized that adenoviral overexpression of IGF-1 (Ad-IGF-1) will
      enhance wound healing and induce angiogenesis through a VEGF-dependent pathway.
      METHODS: Ex vivo: 6-mm full-thickness punch biopsies were obtained from normal
      human skin, and 3-mm full-thickness wounds were created at the center. Skin
      explants were maintained at air liquid interface. Db/db murine model: 8-mm full
      thickness dorsal wounds in diabetic (db/db) mice were created. Treatment groups
      in both human ex vivo and in vivo db/db wound models include 1*10(8) particle
      forming units of Ad-IGF-1 or Ad-LacZ, and phosphate buffered saline (n=4
      5/group). Cytotoxicity (lactate dehydrogenase) was quantified at days 3, 5, and 7
      for the human ex vivo wound model. Epithelial gap closure (hematoxylin and eosin;
      Trichrome), VEGF expression (enzyme-linked immunosorbent assay), and capillary
      density (CD 31+CAPS/HPF) were analyzed at day 7. RESULTS: In the human ex vivo
      organ culture, the adenoviral vectors did not demonstrate any significant
      difference in cytotoxicity compared with phosphate buffered saline. Ad-IGF-1
      overexpression significantly increases basal keratinocyte migration, with no
      significant effect on epithelial gap closure. There was a significant increase in
      capillary density in the Ad-IGF-1 wounds. However, there was no effect on VEGF
      levels in Ad-IGF-1 samples compared with controls. In db/db wounds, Ad-IGF-1
      overexpression significantly improves epithelial gap closure and granulation
      tissue with a dense cellular infiltrate compared with controls. Ad-IGF-1 also
      increases capillary density, again with no significant difference in VEGF levels
      in the wounds compared with control treatments. CONCLUSIONS: In two different
      models, our data demonstrate that adenoviral-mediated gene transfer of IGF-1
      results in enhanced wound healing and induces angiogenesis via a VEGF-independent
      pathway. Understanding the underlying mechanisms of IGF-1 effects on angiogenesis
      may help produce novel therapeutics for chronic wounds or diseases characterized
      by a deficit in neovascularization.

PMID- 24725680
TI  - Different roles of hepatic hypothermic ischemia and ischemic preconditioning in
      chemically induced hepatocarcinogenesis in rats.
AB  - BACKGROUND: Hepatic ischemia-reperfusion (IR) injury, an unfavorable complication
      of hepatectomy, could be prevented by hypothermic ischemia and ischemic
      preconditioning (IPC). However, the effects of these two approaches on
      hepatocarcinogenesis have not been examined. The aim of the study was to
      investigate roles of hypothermic ischemia and IPC in a chemically induced rat
      liver tumor model. METHODS: Twenty-four Sprague-Dawley rats were treated with
      diethylnitrosamine and phenobarbital to induce hepatocellular carcinoma. Rats
      underwent hepatic ischemic injury, hypothermic ischemia, and IPC. Twenty-eight-wk
      old rats were sacrificed to evaluate the morbidity and growth of liver tumor.
      Cytokines were measured at the protein and messenger RNA level. RESULTS: IR
      injury significantly promoted liver tumor development. Intriguingly, hypothermic
      ischemia, but not IPC, delayed liver carcinogenesis, although both of them
      suppressed the hepatic IR injury. IPC-treated rats showed elevated interleukin
      (IL)-6 concentration in the serum and messenger RNA expression in liver. In
      addition, higher levels of IL-6 activated signal transducer and activator of
      transcription 3 in the liver of IPC-treated rats. The hepatic expression of
      target genes of signal transducer and activator of transcription 3 signaling,
      cyclin D1, c-myc, c-fos, and c-jun, all of which might participate in tumor
      progression, increased in IPC group, compared with that of IR group. CONCLUSIONS:
      These data indicated hypothermic ischemia could ameliorate both IR injury and
      liver tumor development. However, IPC, another effective method to prevent
      hepatic IR injury, might exacerbate liver tumor growth. The elevated level of IL
      6 was one of the reasons for the different effects of hypothermic ischemia and
      IPC on hepatocarcinogenesis in rats.

PMID- 24725681
TI  - [Transient apical ballooning syndrome during dobutamine stress echocardiography].
AB  - The transient left ventricular apical ballooning syndrome, also known as Tako
      Tusbo syndrome, has an acute onset, is more common in postmenopausal women, and
      is characterized by transient left ventricular apical ballooning, chest pain,
      electrocardiographic abnormalities, and slight elevation of markers for
      myocardial injury, mimicking a myocardial infarction in patients with no
      significant coronary lesions. However, before making the diagnosis, other causes
      of reversible left ventricular dysfunction must be ruled out, such as
      subarachnoid hemorrhage, pheochromocytoma crisis, acute myocarditis, or the
      presence of tachycardiomyopathy. The case is presented of a patient who developed
      ST elevation electrocardiographic changes with apical transient dyskinesia during
      dobutamine stress echocardiography. 

PMID- 24725682
TI  - Improved multi-level protein-protein interaction prediction with semantic-based
      regularization.
AB  - BACKGROUND: Protein-protein interactions can be seen as a hierarchical process
      occurring at three related levels: proteins bind by means of specific domains,
      which in turn form interfaces through patches of residues. Detailed knowledge
      about which domains and residues are involved in a given interaction has
      extensive applications to biology, including better understanding of the binding
      process and more efficient drug/enzyme design. Alas, most current interaction
      prediction methods do not identify which parts of a protein actually instantiate
      an interaction. Furthermore, they also fail to leverage the hierarchical nature
      of the problem, ignoring otherwise useful information available at the lower
      levels; when they do, they do not generate predictions that are guaranteed to be
      consistent between levels. RESULTS: Inspired by earlier ideas of Yip et al. (BMC
      Bioinformatics 10:241, 2009), in the present paper we view the problem as a multi
      level learning task, with one task per level (proteins, domains and residues),
      and propose a machine learning method that collectively infers the binding state
      of all object pairs. Our method is based on Semantic Based Regularization (SBR),
      a flexible and theoretically sound machine learning framework that uses First
      Order Logic constraints to tie the learning tasks together. We introduce a set of
      biologically motivated rules that enforce consistent predictions between the
      hierarchy levels. CONCLUSIONS: We study the empirical performance of our method
      using a standard validation procedure, and compare its performance against the
      only other existing multi-level prediction technique. We present results showing
      that our method substantially outperforms the competitor in several experimental
      settings, indicating that exploiting the hierarchical nature of the problem can
      lead to better predictions. In addition, our method is also guaranteed to produce
      interactions that are consistent with respect to the protein-domain-residue
      hierarchy.

PMID- 24725683
TI  - Oncology scan-rising stars, fading stars, and shooting stars: new trends in
      prostate cancer management.

PMID- 24725684
TI  - Acceler-dated fractionation: the end of the era of the large, "one size fits all"
      trial for locally advanced head and neck cancer.

PMID- 24725685
TI  - Q&A with Dr Jay S. Cooper about Radiation Therapy Oncology Group 9003.

PMID- 24725686
TI  - Metronomic adjuvant chemotherapy improves treatment outcome in nasopharyngeal
      carcinoma patients with postradiation persistently detectable plasma Epstein-Barr
      virus deoxyribonucleic acid.
AB  - PURPOSE: To investigate the effects of adjuvant chemotherapy in nasopharyngeal
      carcinoma (NPC) patients with persistently detectable plasma Epstein-Barr virus
      DNA (pEBV DNA) after curative radiation therapy plus induction/concurrent
      chemotherapy. METHODS AND MATERIALS: The study population consisted of 625 NPC
      patients with available pEBV DNA levels before and after treatment. Eighty-five
      patients with persistently detectable pEBV DNA after 1 week of completing
      radiation therapy were eligible for this retrospective study. Of the 85 patients,
      33 were administered adjuvant chemotherapy consisting of oral tegafur-uracil (2
      capsules twice daily) for 12 months with (n=4) or without (n=29) preceding
      intravenous chemotherapy of mitomycin-C, epirubicin, and cisplatin. The remaining
      52 patients who did not receive adjuvant chemotherapy served as the control
      group. RESULTS: Baseline patient characteristics at diagnosis (age, sex,
      pathologic type, performance status, T classification, N classification, and
      overall stage), as well as previous treatment modality, were comparable in both
      arms. After a median follow-up of 70 months for surviving patients, 45.5% (15 of
      33 patients) with adjuvant chemotherapy and 71.2% (37 of 52 patients) without
      adjuvant chemotherapy experienced tumor relapses (P=.0323). There were a
      significant reduction in distant failure (P=.0034) but not in local or regional
      recurrence. The 5-year overall survival rate was 71.6% for patients with adjuvant
      chemotherapy and 28.7% for patients without adjuvant chemotherapy (hazard ratio
      0.27; 95% confidence interval 0.17-0.55; P<.0001). CONCLUSIONS: Our retrospective
      data showed that adjuvant chemotherapy can reduce distant failure and improve
      overall survival in NPC patients with persistently detectable pEBV DNA after
      curative radiation therapy plus induction/concurrent chemotherapy.

PMID- 24725687
TI  - Effectiveness of chemoradiation for head and neck cancer in an older patient
      population.
AB  - PURPOSE: The purpose of this study was to compare chemoradiation therapy (CRT)
      with radiation therapy (RT) only in an older patient population with head and
      neck squamous cell carcinoma (HNSCC). METHODS AND MATERIALS: Using the
      Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database (1992
      2007), we identified a retrospective cohort of nonmetastatic HNSCC patients and
      divided them into treatment groups. Comparisons were made between CRT and RT
      cohorts. Propensity scores for CRT were estimated from covariates associated with
      receipt of treatment using multivariable logistic regression. Standardized
      mortality ratio weights (SMRW) were created from the propensity scores and used
      to balance groups on measured confounders. Multivariable and SMR-weighted Cox
      proportional hazard models were used to estimate the hazard ratio (HR) of death
      for receipt of CRT versus RT among the whole group and for separate patient and
      tumor categories. RESULTS: The final cohort of 10,599 patients was 68% male and
      89% white. Median age was 74 years. Seventy-four percent were treated with RT,
      26% were treated with CRT. Median follow-up points for CRT and RT survivors were
      4.6 and 6.3 years, respectively. On multivariable analysis, HR for death with CRT
      was 1.13 (95% confidence interval [CI]: 1.07-1.20; P<.01). Using the SMRW model,
      the HR for death with CRT was 1.08 (95% CI: 1.02-1.15; P=.01). CONCLUSIONS:
      Although the addition of chemotherapy to radiation has proven efficacious in many
      randomized controlled trials, it may be less effective in an older patient
      population treated outside of a controlled trial setting.

PMID- 24725688
TI  - Genetic susceptibility to head and neck squamous cell carcinoma.
AB  - Head-and-neck squamous cell carcinoma (HNSCC) is the sixth most common cancer
      worldwide, and its incidence is growing. Although environmental carcinogens and
      carcinogenic viruses are the main etiologic factors, genetic predisposition
      obviously plays a risk-modulating role, given that not all individuals exposed to
      these carcinogens experience the disease. This review highlights some aspects of
      genetic susceptibility to HNSCC: among others, genetic polymorphisms in
      biotransformation enzymes, DNA repair pathway, apoptotic pathway, human
      papillomavirus-related pathways, mitochondrial polymorphisms, and polymorphism
      related to the bilirubin-metabolized pathway. Furthermore, epigenetic variations,
      familial forms of HNSCC, functional assays for HNSCC risk assessment, and the
      implications and perspectives of research on genetic susceptibility in HNSCC are
      discussed. 

PMID- 24725689
TI  - Modern radiation therapy for nodal non-Hodgkin lymphoma-target definition and
      dose guidelines from the International Lymphoma Radiation Oncology Group.
AB  - Radiation therapy (RT) is the most effective single modality for local control of
      non-Hodgkin lymphoma (NHL) and is an important component of therapy for many
      patients. Many of the historic concepts of dose and volume have recently been
      challenged by the advent of modern imaging and RT planning tools. The
      International Lymphoma Radiation Oncology Group (ILROG) has developed these
      guidelines after multinational meetings and analysis of available evidence. The
      guidelines represent an agreed consensus view of the ILROG steering committee on
      the use of RT in NHL in the modern era. The roles of reduced volume and reduced
      doses are addressed, integrating modern imaging with 3-dimensional planning and
      advanced techniques of RT delivery. In the modern era, in which combined-modality
      treatment with systemic therapy is appropriate, the previously applied extended
      field and involved-field RT techniques that targeted nodal regions have now been
      replaced by limiting the RT to smaller volumes based solely on detectable nodal
      involvement at presentation. A new concept, involved-site RT, defines the
      clinical target volume. For indolent NHL, often treated with RT alone, larger
      fields should be considered. Newer treatment techniques, including intensity
      modulated RT, breath holding, image guided RT, and 4-dimensional imaging, should
      be implemented, and their use is expected to decrease significantly the risk for
      normal tissue damage while still achieving the primary goal of local tumor
      control. 

PMID- 24725690
TI  - Survival and neurocognitive outcomes after cranial or craniospinal irradiation
      plus total-body irradiation before stem cell transplantation in pediatric
      leukemia patients with central nervous system involvement.
AB  - PURPOSE: To evaluate survival and neurocognitive outcomes in pediatric acute
      lymphoblastic leukemia (ALL) patients with central nervous system (CNS)
      involvement treated according to an institutional protocol with stem cell
      transplantation (SCT) and a component of craniospinal irradiation (CSI) in
      addition to total-body irradiation (TBI) as preparative regimen. METHODS AND
      MATERIALS: Forty-one pediatric ALL patients underwent SCT with TBI and received
      additional cranial irradiation or CSI because of CNS leukemic involvement.
      Prospective neurocognitive testing was performed before and after SCT in a subset
      of patients. Cox regression models were used to determine associations of patient
      and disease characteristics and treatment methods with outcomes. RESULTS: All
      patients received a cranial radiation boost; median total cranial dose was 24 Gy.
      Eighteen patients (44%) received a spinal boost; median total spinal dose for
      these patients was 18 Gy. Five-year disease-free survival (DFS) for all patients
      was 67%. Those receiving CSI had a trend toward superior DFS compared with those
      receiving a cranial boost alone (hazard ratio 3.23, P=.14). Patients with
      isolated CNS disease before SCT had a trend toward superior DFS (hazard ratio
      3.64, P=.11, 5-year DFS 74%) compared with those with combined CNS and bone
      marrow disease (5-year DFS 59%). Neurocognitive testing revealed a mean post-SCT
      overall intelligence quotient of 103.7 at 4.4 years. Relative deficiencies in
      processing speed and/or working memory were noted in 6 of 16 tested patients
      (38%). Pre- and post-SCT neurocognitive testing revealed no significant change in
      intelligence quotient (mean increase +4.7 points). At a mean of 12.5 years after
      transplant, 11 of 13 long-term survivors (85%) had completed at least some
      coursework at a 2- or 4-year college. CONCLUSION: The addition of CSI to TBI
      before SCT in pediatric ALL with CNS involvement is effective and well-tolerated.
      Craniospinal irradiation plus TBI is worthy of further protocol investigation in
      children with CNS leukemia.

PMID- 24725691
TI  - Extramedullary relapse following total marrow and lymphoid irradiation in
      patients undergoing allogeneic hematopoietic cell transplantation.
AB  - PURPOSE: Approximately 5% to 20% of patients who undergo total body irradiation
      (TBI) in preparation for hematopoietic cell transplantation (HCT) can develop
      extramedullary (EM) relapse. Whereas total marrow and lymphoid irradiation (TMLI)
      provides a more conformally targeted radiation therapy for patients, organ
      sparing has the potential to place the patient at a higher risk for EM relapse
      than TBI. This study evaluated EM relapse in patients treated with TMLI at our
      institution. METHODS AND MATERIALS: Patients eligible for analysis had been
      enrolled in 1 of 3 prospective TMLI trials between 2006 and 2012. The TMLI
      targeted bones, major lymph node chains, liver, spleen, testes, and brain, using
      image-guided tomotherapy with total dose ranging from 12 to 15 Gy. RESULTS: A
      total of 101 patients with a median age of 47 years were studied. The median
      follow-up was 12.8 months. Incidence of EM relapse and bone marrow (BM) relapse
      were 12.9% and 25.7%, respectively. Of the 13 patients who had EM relapse, 4 also
      had BM relapse, and 7 had EM disease prior to HCT. There were a total of 19 EM
      relapse sites as the site of initial recurrence: 11 soft tissue, 6 lymph node, 2
      skin. Nine of these sites were within the target region and received >=12 Gy. Ten
      initial EM relapse sites were outside of the target region: 5 sites received 10.1
      to 11.4 Gy while 5 sites received <10 Gy. Pretransplantation EM was the only
      significant predictor of subsequent EM relapse. The cumulative incidence of EM
      relapse was 4% at 1 year and 11.4% at 2 years. CONCLUSIONS: EM relapse incidence
      was as frequent in regions receiving >=10 Gy as those receiving <10 Gy. EM
      relapse rates following TMLI that included HCT regimens were comparable to
      published results with regimens including TBI and suggest that TMLI is not
      associated with an increased EM relapse risk.

PMID- 24725692
TI  - Patterns of failure for rhabdomyosarcoma of the perineal and perianal region.
AB  - PURPOSE: To analyze prognostic factors and patterns of failure for
      rhabdomyosarcoma of the perineal and perianal region (PRMS), with an emphasis on
      radiation therapy for locoregional control. METHODS AND MATERIALS: Detailed
      records of all 14 patients treated for PRMS at Memorial Sloan-Kettering Cancer
      Center between 1998 and 2012 were reviewed. The Kaplan-Meier method was used to
      assess the event-free survival (EFS) and overall survival (OS), and a competing
      risks analysis was used to assess the cumulative incidence of local, regional,
      and distant failures. RESULTS: Median age was 15.8 years (range, 1.1-31.9 years).
      High-risk features were identified: 9 of 14 patients (64%) had group 3 disease
      and 3 of 14 (21%) had group 4; 11 of 14 tumors (78%) were alveolar; 12 of 14
      tumors (86%) were >=5 cm; and 9 of 14 patients (64%) had involved lymph nodes
      (N1). Of those aged >=10 years at diagnosis, 9 of 10 (90%) had alveolar
      histology, all had tumors >=5 cm, and 8 of 10 (80%) presented with N1 disease.
      The rates of local, regional, and distant failure at 5 years were 17%, 31%, and
      52%, respectively. Although 3 of the 4 patients with regional failure received
      nodal irradiation, only one of the nodal failures occurred in the radiation
      therapy field. The 5-year EFS was 33%, and OS was 39%. Age >=10 years was
      associated with poor outcomes: EFS was 13% in patients aged >=10 years, compared
      with 75% in those aged <10 years (P=.04); the OS was 13% in patients aged >=10
      years, compared with 100% in those aged <10 years (P=.04). CONCLUSIONS: Patients
      with PRMS, especially those aged >=10 years, present with poor prognostic
      features and continue to have poor outcomes. Given the high incidence of regional
      node recurrence, we recommend prophylactic ilioinguinal lymph node irradiation
      for all patients aged >=10 years. For children aged <10 years, nodal evaluation
      is essential to determine the role for lymph node irradiation.

PMID- 24725693
TI  - Manifestation pattern of early-late vaginal morbidity after definitive radiation
      (chemo)therapy and image-guided adaptive brachytherapy for locally advanced
      cervical cancer: an analysis from the EMBRACE study.
AB  - BACKGROUND AND PURPOSE: Brachytherapy in the treatment of locally advanced
      cervical cancer has changed substantially because of the introduction of combined
      intracavitary/interstitial applicators and an adaptive target concept, which is
      the focus of the prospective, multi-institutional EMBRACE study
      (www.embracestudy.dk) on image-guided adaptive brachytherapy (IGABT). So far,
      little has been reported about the development of early to late vaginal morbidity
      in the frame of IGABT. Therefore, the aim of the present EMBRACE analysis was to
      evaluate the manifestation pattern of vaginal morbidity during the first 2 years
      of follow-up. METHODS AND MATERIALS: In total, 588 patients with a median follow
      up time of 15 months and information on vaginal morbidity were included.
      Morbidity was prospectively assessed at baseline, every 3 months during the first
      year, and every 6 months in the second year according to the Common Terminology
      Criteria for Adverse Events, version 3, regarding vaginal stenosis, dryness,
      mucositis, bleeding, fistula, and other symptoms. Crude incidence rates,
      actuarial probabilities, and prevalence rates were analyzed. RESULTS: At 2 years,
      the actuarial probability of severe vaginal morbidity (grade >=3) was 3.6%.
      However, mild and moderate vaginal symptoms were still pronounced (grade >=1,
      89%; grade >=2, 29%), of which the majority developed within 6 months. Stenosis
      was most frequently observed, followed by vaginal dryness. Vaginal bleeding and
      mucositis were mainly mild and infrequently reported. CONCLUSION: Severe vaginal
      morbidity within the first 2 years after definitive radiation (chemo)therapy
      including IGABT with intracavitary/interstitial techniques for locally advanced
      cervical cancer is limited and is significantly less than has been reported from
      earlier studies. Thus, the new adaptive target concept seems to be a safe
      treatment with regard to the vagina being an organ at risk. However, mild to
      moderate vaginal morbidity is still pronounced with currently applied IGABT, and
      it needs further attention.

PMID- 24725694
TI  - Increasing use of dose-escalated external beam radiation therapy for men with
      nonmetastatic prostate cancer.
AB  - PURPOSE: To examine recent practice patterns, using a large national cancer
      registry, to understand the extent to which dose-escalated external beam
      radiation therapy (EBRT) has been incorporated into routine clinical practice for
      men with prostate cancer. METHODS AND MATERIALS: We conducted a retrospective
      observational cohort study using the National Cancer Data Base, a nationwide
      oncology outcomes database in the United States. We identified 98,755 men
      diagnosed with nonmetastatic prostate cancer between 2006 and 2011 who received
      definitive EBRT and classified patients into National Comprehensive Cancer
      Network (NCCN) risk groups. We defined dose-escalated EBRT as total prescribed
      dose of >=75.6 Gy. Using multivariable logistic regression, we examined the
      association of patient, clinical, and demographic characteristics with the use of
      dose-escalated EBRT. RESULTS: Overall, 81.6% of men received dose-escalated EBRT
      during the study period. The use of dose-escalated EBRT did not vary
      substantially by NCCN risk group. Use of dose-escalated EBRT increased from 70.7%
      of patients receiving treatment in 2006 to 89.8% of patients receiving treatment
      in 2011. On multivariable analysis, year of diagnosis and use of intensity
      modulated radiation therapy were significantly associated with receipt of dose
      escalated EBRT. CONCLUSIONS: Our study results indicate that dose-escalated EBRT
      has been widely adopted by radiation oncologists treating prostate cancer in the
      United States. The proportion of patients receiving dose-escalated EBRT increased
      nearly 20% between 2006 and 2011. We observed high utilization rates of dose
      escalated EBRT within all disease risk groups. Adoption of intensity modulated
      radiation therapy was strongly associated with use of dose-escalated treatment.

PMID- 24725695
TI  - Pretreatment growth rate predicts radiation response in vestibular schwannomas.
AB  - PURPOSE: Vestibular schwannomas (VS) are often followed without initial
      therapeutic intervention because many tumors do not grow and radiation therapy is
      associated with potential adverse effects. In an effort to determine whether
      maximizing initial surveillance predicts for later treatment response, the
      predictive value of preirradiation growth rate of VS on response to radiation
      therapy was assessed. METHODS AND MATERIALS: Sixty-four patients with 65 VS were
      treated with single-fraction stereotactic radiation surgery or fractionated
      stereotactic radiation therapy. Pre- and postirradiation linear expansion rates
      were estimated using volumetric measurements on sequential magnetic resonance
      images (MRIs). In addition, postirradiation tumor volume change was classified as
      demonstrating shrinkage (ratio of volume on last follow-up MRI to MRI immediately
      preceding irradiation <80%), stability (ratio 80%-120%), or expansion (ratio
      >120%). The median pre- and postirradiation follow-up was 20.0 and 27.5 months,
      respectively. Seven tumors from neurofibromatosis type 2 (NF2) patients were
      excluded from statistical analyses. RESULTS: In the 58 non-NF2 patients, there
      was a trend of correlation between pre- and postirradiation volume change rates
      (slope on linear regression, 0.29; P=.06). Tumors demonstrating postirradiation
      expansion had a median preirradiation growth rate of 89%/year, and those without
      postirradiation expansion had a median preirradiation growth rate of 41%/year
      (P=.02). As the preirradiation growth rate increased, the probability of
      postirradiation expansion also increased. Overall, 24.1% of tumors were stable,
      53.4% experienced shrinkage, and 22.5% experienced expansion. Predictors of no
      postirradiation tumor expansion included no prior surgery (P=.01) and slower
      tumor growth rate (P=.02). The control of tumors in NF2 patients was only 43%.
      CONCLUSIONS: Radiation therapy is an effective treatment for VS, but tumors that
      grow quickly preirradiation may be more likely to increase in size. Clinicians
      should take into account tumor growth rate when counseling patients about
      treatment options.

PMID- 24725696
TI  - Correlation of (18)F-FDG avid volumes on pre-radiation therapy and post-radiation
      therapy FDG PET scans in recurrent lung cancer.
AB  - PURPOSE: To investigate the spatial correlation between high uptake regions of 2
      deoxy-2-[(18)F]-fluoro-D-glucose positron emission tomography ((18)F-FDG PET)
      before and after therapy in recurrent lung cancer. METHODS AND MATERIALS: We
      enrolled 106 patients with inoperable lung cancer into a prospective study whose
      primary objectives were to determine first, the earliest time point when the
      maximum decrease in FDG uptake representing the maximum metabolic response (MMR)
      is attainable and second, the optimum cutoff value of MMR based on its predicted
      tumor control probability, sensitivity, and specificity. Of those patients, 61
      completed the required 4 serial (18)F-FDG PET examinations after therapy.
      Nineteen of 61 patients experienced local recurrence at the primary tumor and
      underwent analysis. The volumes of interest (VOI) on pretherapy FDG-PET were
      defined by use of an isocontour at >=50% of maximum standard uptake value
      (SUVmax) (>=50% of SUVmax) with correction for heterogeneity. The VOI on
      posttherapy images were defined at >=80% of SUVmax. The VOI of pretherapy and
      posttherapy (18)F-FDG PET images were correlated for the extent of overlap.
      RESULTS: The size of VOI at pretherapy images was on average 25.7% (range, 8.8%
      56.3%) of the pretherapy primary gross tumor volume (GTV), and their overlap
      fractions were 0.8 (95% confidence interval [CI]: 0.7-0.9), 0.63 (95% CI: 0.49
      0.77), and 0.38 (95% CI: 0.19-0.57) of VOI of posttherapy FDG PET images at 10
      days, 3 months, and 6 months, respectively. The residual uptake originated from
      the pretherapy VOI in 15 of 17 cases. CONCLUSIONS: VOI defined by the SUVmax
      >=50% isocontour may be a biological target volume for escalated radiation dose.

PMID- 24725697
TI  - Changes in functional lung regions during the course of radiation therapy and
      their potential impact on lung dosimetry for non-small cell lung cancer.
AB  - PURPOSE: To study changes in functional activity on ventilation (V)/perfusion (Q)
      single-photon emission computed tomography (SPECT) during radiation therapy (RT)
      and explore the impact of such changes on lung dosimetry in patients with non
      small cell lung cancer (NSCLC). METHODS AND MATERIALS: Fifteen NSCLC patients
      with centrally located tumors were enrolled. All patients were treated with
      definitive RT dose of >=60 Gy. V/Q SPECT-CT scans were performed prior to and
      after delivery of 45 Gy of fractionated RT. SPECT images were used to define
      temporarily dysfunctional regions of lung caused by tumor or other potentially
      reversible conditions as B3. The functional lung (FL) was defined on SPECT by 2
      separate approaches: FL1, a threshold of 30% of the maximum uptake of the
      patient's lung; and FL2, FL1 plus B3 region. The impact of changes in FL between
      initiation of RT and delivery of 45 Gy on lung dosimetry were analyzed. RESULTS:
      Fourteen patients (93%) had larger FL2 volumes than FL1 pre-RT (P<.001).
      Dysfunctional lung became functional in 11 patients (73%) on V SPECT and in 10
      patients (67%) on Q SPECT. The dosimetric parameters generated from CT-based
      anatomical lung had significantly lower values in FL1 than FL2, with a median
      reduction in the volume of lung receiving a dose of at least 20 Gy (V20) of 3%,
      5.6%, and mean lung dose of 0.95 and 1.55 on V and Q SPECT respectively.
      CONCLUSIONS: Regional ventilation and perfusion function improve significantly
      during RT in centrally located NSCLC. Lung dosimetry values vary notably between
      different definitions of functional lung.

PMID- 24725698
TI  - In search of the economic sustainability of Hadron therapy: the real cost of
      setting up and operating a Hadron facility.
AB  - PURPOSE: To determine the treatment cost and required reimbursement for a new
      hadron therapy facility, considering different technical solutions and financing
      methods. METHODS AND MATERIALS: The 3 technical solutions analyzed are a carbon
      only (COC), proton only (POC), and combined (CC) center, each operating 2
      treatment rooms and assumed to function at full capacity. A business model
      defines the required reimbursement and analyzes the financial implications of
      setting up a facility over time; activity-based costing (ABC) calculates the
      treatment costs per type of patient for a center in a steady state of operation.
      Both models compare a private, full-cost approach with public sponsoring, only
      taking into account operational costs. RESULTS: Yearly operational costs range
      between ?10.0M (M = million) for a publicly sponsored POC to ?24.8M for a CC with
      private financing. Disregarding inflation, the average treatment cost calculated
      with ABC (COC: ?29,450; POC: ?46,342; CC: ?46,443 for private financing;
      respectively ?16,059, ?28,296, and ?23,956 for public sponsoring) is slightly
      lower than the required reimbursement based on the business model (between
      ?51,200 in a privately funded POC and ?18,400 in COC with public sponsoring).
      Reimbursement for privately financed centers is very sensitive to a delay in
      commissioning and to the interest rate. Higher throughput and hypofractionation
      have a positive impact on the treatment costs. CONCLUSIONS: Both calculation
      methods are valid and complementary. The financially most attractive option of a
      publicly sponsored COC should be balanced to the clinical necessities and the
      sociopolitical context.

PMID- 24725699
TI  - Lifetime increased cancer risk in mice following exposure to clinical proton beam
      generated neutrons.
AB  - PURPOSE: To evaluate the life span and risk of cancer following whole-body
      exposure of mice to neutrons generated by a passively scattered clinical spread
      out Bragg peak (SOBP) proton beam. METHODS AND MATERIALS: Three hundred young
      adult female FVB/N mice, 152 test and 148 control, were entered into the
      experiment. Mice were placed in an annular cassette around a cylindrical phantom,
      which was positioned lateral to the mid-SOBP of a 165-MeV, clinical proton beam.
      The average distance from the edge of the mid-SOBP to the conscious active mice
      was 21.5 cm. The phantom was irradiated with once-daily fractions of 25 Gy, 4
      days per week, for 6 weeks. The age at death and cause of death (ie, cancer and
      type vs noncancer causes) were assessed over the life span of the mice. RESULTS:
      Exposure of mice to a dose of 600 Gy of proton beam-generated neutrons, reduced
      the median life span of the mice by 4.2% (Kaplan-Meier cumulative survival,
      P=.053). The relative risk of death from cancer in neutron exposed versus control
      mice was 1.40 for cancer of all types (P=.0006) and 1.22 for solid cancers
      (P=.09). For a typical 60 Gy dose of clinical protons, the observed 22% increased
      risk of solid cancer would be expected to decrease by a factor of 10.
      CONCLUSIONS: Exposure of mice to neutrons generated by a proton dose that exceeds
      a typical course of radiation therapy by a factor of 10, resulted in a
      statistically significant increase in the background incidence of leukemia and a
      marginally significant increase in solid cancer. The results indicate that the
      risk of out-of-field second solid cancers from SOBP proton-generated neutrons and
      typical treatment schedules, is 6 to 10 times less than is suggested by current
      neutron risk estimates.

PMID- 24725700
TI  - Four-dimensional patient dose reconstruction for scanned ion beam therapy of
      moving liver tumors.
AB  - PURPOSE: Estimation of the actual delivered 4-dimensional (4D) dose in treatments
      of patients with mobile hepatocellular cancer with scanned carbon ion beam
      therapy. METHODS AND MATERIALS: Six patients were treated with 4 fractions to a
      total relative biological effectiveness (RBE)-weighted dose of 40 Gy (RBE) using
      a single field. Respiratory motion was addressed by dedicated margins and
      abdominal compression (5 patients) or gating (1 patient). 4D treatment dose
      reconstructions based on the treatment records and the measured motion monitoring
      data were performed for the single-fraction dose and a total of 17 fractions. To
      assess the impact of uncertainties in the temporal correlation between motion
      trajectory and beam delivery sequence, 3 dose distributions for varying temporal
      correlation were calculated per fraction. For 3 patients, the total treatment
      dose was formed from the fractional distributions using all possible
      combinations. Clinical target volume (CTV) coverage was analyzed using the
      volumes receiving at least 95% (V95) and 107% (V107) of the planned doses.
      RESULTS: 4D dose reconstruction based on daily measured data is possible in a
      clinical setting. V95 and V107 values for the single fractions ranged between 72%
      and 100%, and 0% and 32%, respectively. The estimated total treatment dose to the
      CTV exhibited improved and more robust dose coverage (mean V95 > 87%, SD < 3%)
      and overdose (mean V107 < 4%, SD < 3%) with respect to the single-fraction dose
      for all analyzed patients. CONCLUSIONS: A considerable impact of interplay
      effects on the single-fraction CTV dose was found for most of the analyzed
      patients. However, due to the fractionated treatment, dose heterogeneities were
      substantially reduced for the total treatment dose. 4D treatment dose
      reconstruction for scanned ion beam therapy is technically feasible and may
      evolve into a valuable tool for dose assessment.

PMID- 24725701
TI  - Dependence of coronary 3-dimensional dose maps on coronary topologies and beam
      set in breast radiation therapy: a study based on CT angiographies.
AB  - PURPOSE: In left-side breast radiation therapy (RT), doses to the left main (LM)
      and left anterior descending (LAD) coronary arteries are usually assessed after
      delineation by prior anatomic knowledge on the treatment planning computed
      tomography (CT) scan. In this study, dose sensitivity due to interindividual
      coronary topology variation was assessed, and hot spots were located. METHODS AND
      MATERIALS: Twenty-two detailed heart models, created from heart computed
      tomography angiographies, were fitted into a single representative female thorax.
      Two breast RT protocols were then simulated into a treatment planning system: the
      first protocol comprised tangential and tumoral bed beams (TGs_TB) at 50 + 16 Gy,
      the second protocol added internal mammary chain beams at 50 Gy to TGs_TB
      (TGs_TB_IMC). For the heart, the LAD, and the LM, several dose indicators were
      calculated: dose-volume histograms, mean dose (Dmean), minimal dose received by
      the most irradiated 2% of the volume (D2%), and 3-dimensional (3D) dose maps.
      Variations of these indicators with anatomies were studied. RESULTS: For the LM,
      the intermodel dispersion of Dmean and D2% was 10% and 11%, respectively, with
      TGs_TB and 40% and 80%, respectively, with TGs_TB_IMC. For the LAD, these
      dispersions were 19% (Dmean) and 49% (D2%) with TGs_TB and 35% (Dmean) and 76%
      (D2%) with TGs_TB_IMC. The 3D dose maps revealed that the internal mammary chain
      beams induced hot spots between 20 and 30 Gy on the LM and the proximal LAD for
      some coronary topologies. Without IMC beams, hot spots between 5 and 26 Gy are
      located on the middle and distal LAD. CONCLUSIONS: Coronary dose distributions
      with hot spot location and dose level can change significantly depending on
      coronary topology, as highlighted by 3D coronary dose maps. In clinical practice,
      coronary imaging may be required for a relevant coronary dose assessment,
      especially in cases of internal mammary chain irradiation.

PMID- 24725702
TI  - Comparison of 4-dimensional computed tomography ventilation with nuclear medicine
      ventilation-perfusion imaging: a clinical validation study.
AB  - PURPOSE: Four-dimensional computed tomography (4DCT) ventilation imaging provides
      lung function information for lung cancer patients undergoing radiation therapy.
      Before 4DCT-ventilation can be implemented clinically it needs to be validated
      against an established imaging modality. The purpose of this work was to compare
      4DCT-ventilation to nuclear medicine ventilation, using clinically relevant
      global metrics and radiologist observations. METHODS AND MATERIALS: Fifteen lung
      cancer patients with 16 sets of 4DCT and nuclear medicine ventilation-perfusion
      (VQ) images were used for the study. The VQ-ventilation images were acquired in
      planar mode using Tc-99m-labeled diethylenetriamine-pentaacetic acid aerosol
      inhalation. 4DCT data, spatial registration, and a density-change-based model
      were used to compute a 4DCT-based ventilation map for each patient. The percent
      ventilation was calculated in each lung and each lung third for both the 4DCT and
      VQ-ventilation scans. A nuclear medicine radiologist assessed the VQ and 4DCT
      scans for the presence of ventilation defects. The VQ and 4DCT-based images were
      compared using regional percent ventilation and radiologist clinical
      observations. RESULTS: Individual patient examples demonstrate good qualitative
      agreement between the 4DCT and VQ-ventilation scans. The correlation coefficients
      were 0.68 and 0.45, using the percent ventilation in each individual lung and
      lung third, respectively. Using radiologist-noted presence of ventilation defects
      and receiver operating characteristic analysis, the sensitivity, specificity, and
      accuracy of the 4DCT-ventilation were 90%, 64%, and 81%, respectively.
      CONCLUSIONS: The current work compared 4DCT with VQ-based ventilation using
      clinically relevant global metrics and radiologist observations. We found good
      agreement between the radiologist's assessment of the 4DCT and VQ-ventilation
      images as well as the percent ventilation in each lung. The agreement lessened
      when the data were analyzed on a regional level. Our study presents an important
      step for the integration of 4DCT-ventilation into thoracic clinical practice.

PMID- 24725703
TI  - Impact of millimeter-level margins on peripheral normal brain sparing for gamma
      knife radiosurgery.
AB  - PURPOSE: To investigate how millimeter-level margins beyond the gross tumor
      volume (GTV) impact peripheral normal brain tissue sparing for Gamma Knife
      radiosurgery. METHODS AND MATERIALS: A mathematical formula was derived to
      predict the peripheral isodose volume, such as the 12-Gy isodose volume, with
      increasing margins by millimeters. The empirical parameters of the formula were
      derived from a cohort of brain tumor and surgical tumor resection cavity cases
      (n=15) treated with the Gamma Knife Perfexion. This was done by first adding
      margins from 0.5 to 3.0 mm to each individual target and then creating for each
      expanded target a series of treatment plans of nearly identical quality as the
      original plan. Finally, the formula was integrated with a published logistic
      regression model to estimate the treatment-induced complication rate for
      stereotactic radiosurgery when millimeter-level margins are added. RESULTS:
      Confirmatory correlation between the nominal target radius (ie, RT) and commonly
      used maximum target size was found for the studied cases, except for a few
      outliers. The peripheral isodose volume such as the 12-Gy volume was found to
      increase exponentially with increasing Delta/RT, where Delta is the margin size.
      Such a curve fitted the data (logarithmic regression, R(2) >0.99), and the 12-Gy
      isodose volume was shown to increase steeply with a 0.5- to 3.0-mm margin applied
      to a target. For example, a 2-mm margin on average resulted in an increase of 55%
      +/- 16% in the 12-Gy volume; this corresponded to an increase in the symptomatic
      necrosis rate of 6% to 25%, depending on the Delta/RT values for the target.
      CONCLUSIONS: Millimeter-level margins beyond the GTV significantly impact
      peripheral normal brain sparing and should be applied with caution. Our model
      provides a rapid estimate of such an effect, particularly for large and/or
      irregularly shaped targets.

PMID- 24725704
TI  - Reporting of uncertainty at the 2013 annual meeting of the American Society for
      Radiation Oncology.
AB  - PURPOSE: The annual meeting of the American Society for Radiation Oncology
      (ASTRO) is designed to disseminate new scientific findings and technical advances
      to professionals. Best practices of scientific dissemination require that some
      level of uncertainty (or imprecision) is provided. METHODS AND MATERIALS: A total
      of 279 scientific abstracts were selected for oral presentation in a clinical
      session at the 2013 ASTRO Annual Meeting. A random sample of these abstracts was
      reviewed to determine whether a 95% confidence interval (95% CI) or analogous
      measure of precision was provided for time-to-event analyses. RESULTS: A sample
      of 140 abstracts was reviewed. Of the 65 abstracts with Kaplan-Meier or
      cumulative incidence analyses, 6 included some measure of precision (6 of 65 =
      9%; 95% CI, 2-16). Of the 43 abstracts reporting ratios for time-to-event
      analyses (eg, hazard ratio, risk ratio), 22 included some measure of precision
      (22 of 43 = 51%; 95% CI, 36-66). CONCLUSIONS: Measures of precision are not
      provided in a significant percentage of abstracts selected for oral presentation
      at the Annual Meeting of ASTRO.

PMID- 24725705
TI  - In reply to Basu et al.

PMID- 24725706
TI  - An anatomically validated brachial plexus contouring method for intensity
      modulated radiation therapy planning. In regard to Van de Velde et al.

PMID- 24725708
TI  - The effect of signal acquisition and processing choices on ApEn values: towards a
      "gold standard" for distinguishing effort levels from isometric force records.
AB  - Approximate entropy (ApEn) is frequently used to identify changes in the
      complexity of isometric force records with ageing and disease. Different signal
      acquisition and processing parameters have been used, making comparison or
      confirmation of results difficult. This study determined the effect of sampling
      and parameter choices by examining changes in ApEn values across a range of
      submaximal isometric contractions of the first dorsal interosseus. Reducing the
      sample rate by decimation changed both the value and pattern of ApEn values
      dramatically. The pattern of ApEn values across the range of effort levels was
      not sensitive to the filter cut-off frequency, or the criterion used to extract
      the section of data for analysis. The complexity increased with increasing effort
      levels using a fixed 'r' value (which accounts for measurement noise) but
      decreased with increasing effort level when 'r' was set to 0.1 of the standard
      deviation of force. It is recommended isometric force records are sampled at
      frequencies >200Hz, template length ('m') is set to 2, and 'r' set to measurement
      system noise or 0.1SD depending on physiological process to be distinguished. It
      is demonstrated that changes in ApEn across effort levels are related to changes
      in force gradation strategy. 

PMID- 24725707
TI  - Optimization of heterologous protein production in Chinese hamster ovary cells
      under overexpression of spliced form of human X-box binding protein.
AB  - BACKGROUND: The optimization of protein production is a complex and challenging
      problem in biotechnology. Different techniques for transcription, translation
      engineering and the optimization of cell culture conditions have been used to
      improve protein secretion, but there remain many open problems involving post
      translational modifications of the secreted protein and cell line stability.
      RESULTS: In this work, we focus on the regulation of secreted protein specific
      productivity (using a recombinant human immunoglobulin G (IgG)) by controlling
      the expression of the spliced form of human X-box binding protein (XBP-(s)) in
      Chinese hamster ovary cells (CHO-K1) under doxycycline (DOX) induction at
      different temperatures. We observed a four-fold increase in specific IgG
      productivity by CHO cells under elevated concentrations of DOX at 30 degrees C
      compared to 37 degrees C, without detectable differences in binding activity in
      vitro or changes in the structural integrity of IgG. In addition, we found a
      correlation between the overexpression of human XBP-1(s) (and, as a consequence,
      endoplasmic reticulum (ER) size expansion) and the specific IgG productivity
      under DOX induction. CONCLUSIONS: Our data suggest the T-REx system
      overexpressing human XBP-1(s) can be successfully used in CHO-K1 cells for human
      immunoglobulin production.

PMID- 24725710
TI  - Introduction.

PMID- 24725709
TI  - Between-centre variability in transfer function analysis, a widely used method
      for linear quantification of the dynamic pressure-flow relation: the CARNet
      study.
AB  - Transfer function analysis (TFA) is a frequently used method to assess dynamic
      cerebral autoregulation (CA) using spontaneous oscillations in blood pressure
      (BP) and cerebral blood flow velocity (CBFV). However, controversies and
      variations exist in how research groups utilise TFA, causing high variability in
      interpretation. The objective of this study was to evaluate between-centre
      variability in TFA outcome metrics. 15 centres analysed the same 70 BP and CBFV
      datasets from healthy subjects (n=50 rest; n=20 during hypercapnia); 10
      additional datasets were computer-generated. Each centre used their in-house TFA
      methods; however, certain parameters were specified to reduce a priori between
      centre variability. Hypercapnia was used to assess discriminatory performance and
      synthetic data to evaluate effects of parameter settings. Results were analysed
      using the Mann-Whitney test and logistic regression. A large non-homogeneous
      variation was found in TFA outcome metrics between the centres. Logistic
      regression demonstrated that 11 centres were able to distinguish between normal
      and impaired CA with an AUC>0.85. Further analysis identified TFA settings that
      are associated with large variation in outcome measures. These results indicate
      the need for standardisation of TFA settings in order to reduce between-centre
      variability and to allow accurate comparison between studies. Suggestions on
      optimal signal processing methods are proposed. 

PMID- 24725711
TI  - Reoperations for pediatric and congenital heart disease: an analysis of the
      Society of Thoracic Surgeons (STS) congenital heart surgery database.
AB  - In this descriptive analysis, data in the Society of Thoracic Surgeons (STS)
      Congenital Heart Surgery Database pertaining to patients who underwent
      reoperative cardiac surgery were analyzed. Practice patterns and outcomes are
      described. Reoperative cardiac surgery for congenital heart disease is common,
      with one third of index operations in the database occurring subsequent to prior
      cardiothoracic operation(s) performed on cardiopulmonary bypass. This analysis
      suggests that a history of previous cardiac surgery does not independently confer
      a significant incremental risk of operative mortality, but that patients with
      greater number of previous operations appear to be at higher risk. 

PMID- 24725712
TI  - Strategies for high-risk reoperations in congenital heart disease.
AB  - Adults with congenital heart disease (CHD) is a rapidly growing group of
      patients, and part of this is owing to the improvement in survival for the vast
      majority of infants with CHD who have undergone successful surgery and live well
      into adult years. Residual or recurrent lesions may precipitate the need for
      reoperation and some patients require numerous surgical procedures or
      interventions over a lifetime. This article will review the surgical issues
      associated with reoperation in patients with CHD and discuss the different
      perioperative strategies that serve to decrease the risk of reoperation. 

PMID- 24725713
TI  - When repair is not feasible: prosthesis selection in children and adults with
      congenital heart disease.
AB  - Congenital heart surgeons face many challenges when dealing with valvular
      pathology in the pediatric population. Because of the concerns related to growth,
      repair should be the main goal. However, this is not always feasible and valve
      replacement becomes the only other alternative. Valve replacement also represents
      one of the most common procedures performed for adults with congenital heart
      disease, with several valve options existing including homografts, xenografts,
      autografts, and other artificial prostheses. The choice sometimes may be
      difficult because there are advantages and disadvantages to each valve
      substitute. In this article, we will address the different options of valve
      replacement in children and adults with congenital heart disease, and review the
      current literature that supports current practice. 

PMID- 24725714
TI  - Tetralogy of fallot and pulmonary valve replacement: timing and techniques in the
      asymptomatic patient.
AB  - An increasing number of survivors of congenital heart disease will require repeat
      surgical intervention. In the tetralogy of Fallot population, the primary
      indication is for pulmonary valve replacement secondary to pulmonary
      regurgitation. Although pulmonary valve disruption during repair is initially
      well tolerated, by the second decade following repair, patients develop increased
      right ventricular size with potentially decreased function. It is now well
      accepted that patients experiencing symptoms of heart failure secondary to
      chronic pulmonary insufficiency undergo pulmonary valve replacement. However, in
      the asymptomatic population, indications and timing of valve replacement are less
      clear. This article examines the current literature and presents guidelines
      regarding pulmonary valve replacement in the asymptomatic patient. Also, in the
      current era of percutaneous valve replacement, certain technical considerations
      should be given toward valve replacement and are discussed as well. 

PMID- 24725715
TI  - A modification of the pulmonary autograft procedure to prevent late autograft
      dilatation.
AB  - Although the pulmonary autograft procedure for aortic valve replacement is a
      commonly utilized option for children, its use is diminishing in adult-aged
      patients. One commonly cited concern is the tendency for the pulmonary autograft
      to dilate in the aortic position. This article reviews a technique we have used
      in 36 patients since October, 2004 that stabilizes the autograft so that it
      cannot dilate. There have been no operative or late deaths and the autograft has
      continued to function in 34 patients. Two patients have undergone autograft
      replacement because of early failure, which we believe was likely related to
      technical considerations in our early technique (first reported in the 2005 STCVS
      Pediatric Cardiac Surgery Annual). The technical modifications described in this
      article have produced a more reliable and reproducible technique and have not
      resulted in any autograft failures in our experience. One patient with Marfan's
      syndrome and a bicuspid aortic valve is symptom- and dilation-free 8 years post
      op, with no autograft or pulmonary homograft insufficiency, normal activity and a
      stable aortic root by serial echocardiography. Our results suggest that this
      technique might be applicable for selected adult patients in whom autograft
      growth is not necessary and for whom the risk of autograft dilatation would
      provide a reason to avoid a pulmonary autograft procedure. 

PMID- 24725716
TI  - Reoperation for left ventricular outflow tract obstruction after repair of
      atrioventricular septal.
AB  - Left ventricular outflow tract obstruction (LVOTO) is an important source of
      morbidity and mortality after repair of atrioventricular septal defect (AVSD).
      The intrinsic anatomy of the left ventricular outflow tract in AVSD is complex
      and predisposes to the development of LVOTO. LVOTO after repair of AVSD usually
      involves multiple levels and sources of obstruction, and surgical intervention
      must address each component of the obstruction. This includes fibromuscular
      obstruction, septal hypertrophy, and valve related sources of obstruction.
      Special attention is also directed to the anterolateral muscle bundle of the left
      ventricle, a well defined but under recognized feature of the left ventricular
      outflow tract in AVSD. It is present in all patients with AVSD, and resection of
      a hypertrophic anterolateral muscle bundle of the left ventricle should be
      incorporated in all operations for LVOTO after repair of AVSD. LVOTO after repair
      of AVSD has several unique features that must be taken into consideration to
      maximize outcome after surgical intervention. These include anatomic factors,
      technical aspects of surgical intervention, and proper selection of the operation
      used for relief of LVOTO. 

PMID- 24725717
TI  - Reoperation after vascular ring repair.
AB  - The majority of patients having surgical intervention for a vascular ring have
      resolution of their symptoms. However, 5% to 10% of these patients develop
      recurrent symptoms related either to airway or esophageal compression and may
      require reoperation. In our series of 300 patients with vascular rings, we
      performed a reoperation on 26 patients, not all of whom were originally operated
      on at our institution. The four primary indications for reoperation were
      Kommerell diverticulum (n = 18), circumflex aorta (n = 2), residual scarring (n =
      2), and tracheobronchomalacia requiring aortopexy (n = 4). All patients
      undergoing reoperation have had preoperative evaluation with bronchoscopy and
      computed tomographic scanning (CT) with 3-dimensional reconstruction. Patients
      with dysphagia have had a barium esophagram and esophagoscopy. Patients with a
      Kommerell diverticulum have undergone resection of the diverticulum and transfer
      of the left subclavian artery to the left carotid artery. The aortic uncrossing
      procedure has been used in patients with a circumflex aorta. Aortopexy has been
      used to treat anterior compression of the trachea by the aorta. Results of these
      reinterventions have been successful in nearly all cases. Lessons learned from
      these reoperations can be applied to prevent the need for reoperation by properly
      selecting the correct initial operation. A dedicated team caring for these
      children consisting of medical imaging, otolaryngology, cardiovascular-thoracic
      surgery, and critical care is imperative. 

PMID- 24725718
TI  - Scimitar syndrome: the curved Turkish sabre.
AB  - Scimitar syndrome is a rare association of congenital cardiopulmonary anomalies
      characterized by an anomalous pulmonary vein (scimitar vein) that drains into the
      inferior vena cava, a hypogenetic right lung, and dextroposition of the heart. It
      has been reported in 3% to 6% of patients with partial anomalous pulmonary venous
      connection. Patients are either diagnosed early with severe symptoms (infantile
      type) or late with minimal symptoms (childhood/adult type). In this chapter we
      reviewed the history, pathophysiology, presentation, diagnosis, and treatment
      methods of Scimitar syndrome in the current era. 

PMID- 24725719
TI  - Mechanical circulatory support: strategies and outcomes in pediatric congenital
      heart disease.
AB  - Patients with acute or progressive heart failure in the setting of congenital
      heart disease may need mechanical circulatory support (MCS) to enhance survival
      while awaiting cardiac transplantation. Because the majority of MCS devices are
      implanted after prior cardiac operations, special precautions are necessary at
      the time of implant. MCS in single ventricle patients usually requires
      ventricular and aortic cannulation, with a systemic to pulmonary artery shunt for
      pulmonary blood flow. Limited outcomes data is available, with less than 15% of
      pediatric MCS patients having congenital heart disease. The Berlin EXCOR is the
      only durable device currently available for infants. Neurologic complications are
      the major cause of mortality, and survival during support is poor for infants <5
      kg. Patients post-Fontan with acute cardiac failure and/or respiratory failure
      are at high risk for death before transplant and should be considered for MCS
      therapy. Several emerging miniature continuous flow devices will soon broaden the
      landscape of available pediatric devices. 

PMID- 24725720
TI  - Heart transplantation in children for end-stage congenital heart disease.
AB  - Heart transplantation (HT) as primary therapy for children with congenital heart
      disease (CHD) has become unusual. With improved early results of reconstructive
      surgery, the population of children and adults surviving with CHD is expanding.
      End-stage CHD related to myocardial dysfunction or circulation failure after
      prior surgery is becoming more common as an indication for HT. This heterogeneous
      group of CHD recipients referred for HT presents unique decision-making,
      technical, and physiologic challenges. Historically, a diagnosis of CHD has been
      a major risk factor for early mortality after HT. Rescue HT, especially in the
      setting of failing Fontan physiology, has the worst outcome. Early referral
      (before end-organ damage), proper selection, and optimization of recipients, as
      well as meticulous intra- and postoperative management are crucial to improving
      early outcomes of HT in this population. Beyond the early post-HT period,
      children with end-stage CHD experience long-term survival comparable to most
      other non-CHD recipients. 

PMID- 24725721
TI  - Neuroprotective strategies--what do we really need to know?
AB  - While preliminary data are encouraging, definitive data are lacking to
      conclusively demonstrate the benefit of perioperative neurologic monitoring in
      improving neurodevelopmental outcomes in children who require surgery for
      congenital heart disease. Nonetheless, in the current era, some form of
      perioperative neurologic monitoring is important. Strategies include bicortical
      near infrared spectroscopy monitoring in the pre- and postoperative periods along
      with bicortical near infrared spectroscopy and transcranial Doppler
      intraoperatively. These monitors provide real-time information concerning
      cerebral oxygen delivery and blood flow. These strategies will allow us to refine
      treatments to optimize neurodevelopmental potential in children with congenital
      heart disease. 

PMID- 24725722
TI  - All this monitoring...what's necessary, what's not?
AB  - The goal of perioperative monitoring is to aid the clinician in optimizing care
      to achieve the best possible survival with the lowest possible morbidity.
      Ideally, we would like to have monitoring that can rapidly and accurately
      identify perturbations in circulatory well-being that would permit timely
      intervention and allow for restoration before the patient is damaged. The
      evidence to support the use of our standard monitoring strategies (continuous
      electrocardiography, blood pressure, central venous pressure, oxygen saturation
      and capnography) is based on expert opinion, case series, or at best
      observational studies. While these monitoring parameters will identify life
      threatening events, they provide no direct information concerning the oxygen
      economy of the patient. Nevertheless, they are mandated by professional societies
      representing specialists in cardiac disease, critical care, and anesthesiology.
      Additional non-routine monitoring strategies that provide data concerning the
      body's oxygen economy, such as venous saturation monitoring and near infrared
      spectroscopy, have shown promise in prospective observational studies in managing
      these complex groups of patients. Ideally, high-level evidence would be required
      before adopting these newer strategies, but in the absence of new funding sources
      and the challenges of the wide variation in practice patterns between centers,
      this seems unlikely. The evidence supporting the current standard perioperative
      monitoring strategies will be reviewed. In addition, evidence supporting non
      routine monitoring strategies will be reviewed and their potential for added
      benefit assessed. 

PMID- 24725723
TI  - Mechanical assist devices in neonates and infants.
AB  - Clinical advances in the field of mechanical support have led to additional
      treatment strategies in adult and, subsequently, pediatric heart failure
      management. The limited number of device options available to the pediatric
      population has led to a reallocation of resources in order to broaden the
      pediatric device armamentarium. Although there are very few device options in
      pediatrics, there are short-term support options that include the RotaFlow and
      PediMag. The longer-term support option for small children is limited to only the
      Berlin heart EXCOR device, which had been approved by the FDA since December
      2011. There is a dire need for further device options for the pediatric patient
      and many devices funded by the PumpKIN program are under development to further
      the care of this population. 

PMID- 24725724
TI  - CODEX-aligned dietary fiber definitions help to bridge the 'fiber gap'.
AB  - A comprehensive dietary fiber (DF) definition was adopted by the CODEX
      Alimentarius Commission (CAC) (1) to reflect the current state of knowledge about
      DF, (2) to recognize that all substances that behave like fiber regardless of how
      they are produced can be named as DF if they show physiological benefits, and (3)
      to promote international harmonization for food labeling and food composition
      tables. This review gives the history and evolution of the state of DF knowledge
      as looked at by refinements in DF methods and definitions subsequent to the
      launch of the DF hypothesis. The refinements parallel both interventional and
      epidemiological research leading to better understanding of the role of DF in
      contributing to the numerous physiological benefits imparted by all the various
      digestion resistant carbohydrates. A comparison of the CODEX definition
      (including its footnote that authorizes the inclusion of polymers with DP 3-9)
      and approved CODEX Type 1 methods with other existing definitions and methods
      will point out differences and emphasize the importance of adoption of CODEX
      aligned definitions by all jurisdictions. Such harmonization enables comparison
      of nutrition research, recommendations, food composition tables and nutrition
      labels the world over. A case will be made that fibers are analogous to vitamins,
      in that they vary in structure, function and amount needed, but each when present
      in the right amount contributes to optimal health. Since the intake of DF is
      significantly below recommended levels throughout the world, the recognition that
      'all fibers fit' is an important strategy in bridging the 'fiber gap' by
      enfranchising and encouraging greater intake of foods with inherent and added DF.
      Fortifying foods with added DF makes it easier to increase intakes while
      maintaining calories at recommended levels. 

PMID- 24725725
TI  - Re: Shoulder silhouette and axilla reconstruction with free composite elbow
      tissue transfer following interscapulothoracic amputation.

PMID- 24725726
TI  - Reply: Venous thromboembolism prophylaxis for abdominal free tissue breast
      reconstruction: a multicentre survey.

PMID- 24725727
TI  - Another suspected case of breast cancer recurrence after lipofilling? Remain
      cautious ....

PMID- 24725728
TI  - Treatment of hypergranulation tissue with intralesional injection of
      corticosteroids: preliminary results.

PMID- 24725729
TI  - Low-load/high-repetition elastic band resistance training in patients with COPD:
      a randomized, controlled, multicenter trial.
AB  - BACKGROUND AND AIMS: High-repetitive resistance training (RT) is recommended to
      increase peripheral muscular endurance in healthy adults; however, the effects of
      RT with this design on exercise capacity and health-related quality of life
      (HRQOL) in patients with chronic obstructive pulmonary disease (COPD) is unknown.
      The study aimed to investigate if low-load/high-repetition elastic band RT could
      improve functional capacity, muscular function, endurance cycle capacity or HRQOL
      in patients with COPD. METHODS: A prospective, randomized, controlled,
      multicentre trial was constructed with concealed allocation, blinded outcome
      assessment and intention-to-treat analysis. A total of 44 patients with moderate
      to-very-severe COPD (forced expiratory volume during the first second, 44.6%
      predicted) were included. Patients were randomized to either the experimental
      group receiving 8 weeks of RT (three sessions/week) in combination with patient
      education (four occasions) or the control group receiving the patient education
      alone. RESULTS: At post-tests, the between-group differences were in favor of the
      experimental group on the 6-min walk test [mean difference (95% confidence
      interval)]: 34 m (14-54) and the 6-min pegboard and ring test [20 rings (3-37)].
      No difference between groups was found on the chronic respiratory disease
      questionnaire [0.1 (-0.2 to 0.4)]. On secondary outcomes, results were in favor
      of the experimental group regarding upper extremity endurance capacity, muscular
      function and depression, but no difference was seen between groups on endurance
      cycle capacity and HRQOL. CONCLUSION: RT can increase functional capacity and
      muscular function but not cycle endurance capacity and HRQOL in patients with
      moderate-to-severe COPD.

PMID- 24725730
TI  - Which older people decline participation in a primary care trial of physical
      activity and why: insights from a mixed methods approach.
AB  - BACKGROUND: Physical activity is of vital importance to older peoples' health.
      Physical activity intervention studies with older people often have low
      recruitment, yet little is known about non-participants. METHODS: Patients aged
      60-74 years from three UK general practices were invited to participate in a
      nurse-supported pedometer-based walking intervention. Demographic characteristics
      of 298 participants and 690 non-participants were compared. Health status and
      physical activity of 298 participants and 183 non-participants who completed a
      survey were compared using age, sex adjusted odds ratios (OR) (95% confidence
      intervals). 15 non-participants were interviewed to explore perceived barriers to
      participation. RESULTS: Recruitment was 30% (298/988). Participants were more
      likely than non-participants to be female (54% v 47%; p = 0.04) and to live in
      affluent postcodes (73% v 62% in top quintile; p < 0.001). Participants were more
      likely than non-participants who completed the survey to have an occupational
      pension OR 2.06 (1.35-3.13), a limiting longstanding illness OR 1.72 (1.05-2.79)
      and less likely to report being active OR 0.55 (0.33-0.93) or walking fast OR
      0.56 (0.37-0.84). Interviewees supported general practice-based physical activity
      studies, particularly walking, but barriers to participation included: already
      sufficiently active, reluctance to walk alone or at night, physical symptoms,
      depression, time constraints, trial equipment and duration. CONCLUSION: Gender
      and deprivation differences suggest some selection bias. However, trial
      participants reported more health problems and lower activity than non
      participants who completed the survey, suggesting appropriate trial selection in
      a general practice population. Non-participant interviewees indicated that
      shorter interventions, addressing physical symptoms and promoting confidence in
      pursuing physical activity, might increase trial recruitment and uptake of
      practice-based physical activity endeavours.

PMID- 24725731
TI  - Motor recovery patterns in arm muscles: coupled bilateral training and
      neuromuscular stimulation.
AB  - BACKGROUND: Neuromuscular stimulation coupled with bilateral movements
      facilitates functional motor recovery of the upper extremities post stroke. This
      study investigated electromyography activation patterns during training. The
      leading question asked: Do EMG activation patterns show rehabilitative effects of
      coupled bilateral movement training on wrist and fingers extension, elbow
      extension, and shoulder abduction? METHODS: Twelve stroke volunteers completed
      nine hours of coupled bilateral movement training on three sets of joints in
      their arms. Neuromuscular stimulation on the impaired limb assisted wrist and
      fingers extension, elbow extension, and shoulder abduction. Mean activation level
      data were analyzed in a three-way completely within-subjects ANOVA (Training Day
      * Movement Type * Trial Block: 3 * 3 * 3). RESULTS: The analysis revealed three
      important findings: (a) activation levels in Days 5 and 6 were significantly
      higher than Days 1 and 2, (b) muscle activation patterns increased across trial
      blocks, and (c) movements for the shoulder joint/girdle as well as wrist and
      fingers demonstrated higher activation than the elbow joint. Further analysis
      indicated that the muscle activation patterns for shoulder abduction were
      positively associated with force stabilization (ratio of good variability
      relative to bad variability) during bilateral force production. CONCLUSIONS: The
      findings indicate that capability to increase muscle activity during the three
      joint movements was improved after training. There appears to be higher muscle
      activation in the primary proximal and distal muscles necessary for motor control
      improvement.

PMID- 24725732
TI  - Periviable birth: executive summary of a joint workshop by the Eunice Kennedy
      Shriver National Institute of Child Health and Human Development, Society for
      Maternal-Fetal Medicine, American Academy of Pediatrics, and American College of
      Obstetricians and Gynecologists.
AB  - This is an executive summary of a workshop on the management and counseling
      issues of women anticipated to deliver at a periviable gestation (broadly defined
      as 20 0/7 through 25 6/7 weeks of gestation) and the treatment options for the
      newborn infant. Upon review of the available literature, the workshop panel noted
      that the rates of neonatal survival and neurodevelopmental disabilities among the
      survivors vary greatly across the periviable gestations and are significantly
      influenced by the obstetric and neonatal management practices (eg, antenatal
      steroid, tocolytic agents, and antibiotic administration; cesarean birth; and
      local protocols for perinatal care, neonatal resuscitation, and intensive care
      support). These are, in turn, influenced by the variations in local and regional
      definitions of limits of viability. Because of the complexities in making
      difficult management decisions, obstetric and neonatal teams should confer prior
      to meeting with the family, when feasible. Family counseling should be
      coordinated with the goal of creating mutual trust, respect, and understanding
      and should incorporate evidence-based counseling methods. Since clinical
      circumstances can change rapidly with increasing gestational age, counseling
      should include discussion of the benefits and risks of various maternal and
      neonatal interventions at the time of counseling. There should be a plan for
      follow-up counseling as clinical circumstances evolve. The panel proposed a
      research agenda and recommended developing educational curricula on the care and
      counseling of families facing the birth of a periviable infant.

PMID- 24725733
TI  - Comprehensive characterization of immunoglobulin gene rearrangements in patients
      with chronic lymphocytic leukaemia.
AB  - Previous studies have suggested a geographical pattern of immunoglobulin
      rearrangement in chronic lymphocytic leukaemia (CLL), which could be as a result
      of a genetic background or an environmental antigen. However, the characteristics
      of Ig rearrangements in the population from the South of France have not yet been
      established. Here, we studied CLL B-cell repertoire and mutational pattern in a
      Southern French cohort of patients using an in-house protocol for whole
      sequencing of the rearranged immunoglobulin heavy-chain genes. Described biased
      usage of variable, diversity and joining genes between the mutated and unmutated
      groups was found in our population. However, variable gene frequencies are more
      in accordance with those observed in the Mediterranean patients. We found that
      the third complementary-determining region (CDR) length was higher in unmutated
      sequences, because of bias in the diversity and joining genes usage and not due
      to the N diversity. Mutations found in CLL followed the features of canonical
      somatic hypermutation mechanism: preference of targeting for activation-induced
      cytidine deaminase and polymerase motifs, base change bias for transitions and
      more replacement mutations occurring in CDRs than in framework regions.
      Surprisingly, localization of activation-induced cytidine deaminase motifs onto
      the variable gene showed a preference for framework regions. The study of the
      characteristics at the age of diagnosis showed no difference in clinical outcome,
      but suggested a tendency of increased replacement and transition-over
      transversion mutations and a longer third CDR length in older patients. 

PMID- 24725734
TI  - Thiamine deficiency: the importance of recognition and prompt management.

PMID- 24725735
TI  - A proposal for improved helium microscopy.
AB  - Elimination of the electrostatic objective lens and alternative use of a Cc- and
      Cs-corrected quadrupole doublet may increase the useful working distance of the
      helium microscope, improve its resolution from 3 to 0.3 A, and improve its
      optimum convergence angle from 0.4 to 4 mrad.

PMID- 24725736
TI  - Methicillin-resistant Staphylococcus aureus infection epidemiology and clinical
      response from tigecycline soft tissue infection trials.
AB  - Given increasing resistance, therapeutic options to treat MRSA soft tissue
      infections should be evaluated. This pooled analysis evaluated data from subjects
      enrolled in 6 tigecycline clinical trials with documented MRSA complicated skin
      and skin structure infections or diabetic foot infections (DFIs). Baseline
      characteristics were compared between subjects with and without molecularly
      classified community-acquired (CA) MRSA, specifically staphylococcal cassette
      chromosome mec (SCCmec) IV. Clinical response was compared by CA-MRSA designation
      and treatment group. A total of 378 subjects with MRSA soft tissue infections
      were identified, including 79 with DFI. A total of 249 (65.9%) were molecularly
      classified as CA-MRSA. Clinical response rates for MRSA soft tissue infection
      were similar between tigecycline and vancomycin (treatment difference, 1.0%; 95%
      confidence interval: -9.3, 12.0) as well as by infection type, SCCmec, and Panton
      Valentine leukocidin (PVL) status. Tigecycline demonstrated comparable efficacy
      for treatment of MRSA soft tissue infections regardless of infection type,
      SCCmec, or PVL status. 

PMID- 24725737
TI  - Breaking the limit: mechanical characterization of overexpanded balloon
      expandable stents used in congenital heart disease.
AB  - OBJECTIVE: Intravascular stent placement in patients with congenital heart
      disease has replaced several surgical procedures because the desired outcome is
      achieved with a lower risk of complications. However, the blood vessels of
      children undergo a two- to threefold diameter increase due to somatic growth
      creating a dilemma: Can stents implanted in infants and children be serially
      dilated to significantly larger diameters without losing integrity and important
      mechanical characteristics? Our aim was to assess the expansion potential and to
      characterize mechanical parameters of balloon expandable stents at the maximum
      expansion diameter. DESIGN: Sixteen commonly used stent designs were evaluated.
      Physical attributes (sheath size and guide wire size) and the following
      mechanical parameters were determined, compared, and contrasted: fracture
      diameter, maximum expansion diameter, stent integrity, outer diameter, diameter
      uniformity, diameter recoil, length change, radial stiffness, and radial
      strength. RESULTS: Stents were dilated to an average of 1.7 times (range from 1.3
      to 2.4 times) the nominal expansion diameter without losing mechanical integrity.
      Stents at the maximum expansion diameter maintained diameter uniformity (with
      less than 3.2% difference) and demonstrated minimal diameter recoil once the
      balloon catheter was deflated (less than 3.6% recoil). At the maximum expansion
      diameter, stent length varied depending on stent type. When dilated to the
      maximum expansion diameter, radial stiffness and radial strength of all stents
      increased compared with the stents' nominal expansion diameter. CONCLUSIONS:
      Balloon expandable stents maintain excellent mechanical characteristics when
      dilated beyond their manufacturers' recommended nominal expansion diameter. These
      results support the use of balloon expandable stents in smaller vessels that
      require future serial redilation.

PMID- 24725738
TI  - Pediatricians' and health visitors' views towards detection and management of
      maternal depression in the context of a weak primary health care system: a
      qualitative study.
AB  - BACKGROUND: The present study's aim has been to investigate, identify and
      interpret the views of pediatric primary healthcare providers on the recognition
      and management of maternal depression in the context of a weak primary healthcare
      system. METHODS: Twenty six pediatricians and health visitors were selected by
      using purposive sampling. Face to face in-depth interviews of approximately 45
      minutes duration were conducted. The data were analyzed by using the framework
      analysis approach which includes five main steps: familiarization, identifying a
      thematic framework, indexing, charting, mapping and interpretation. RESULTS: Fear
      of stigmatization came across as a key barrier for detection and management of
      maternal depression. Pediatric primary health care providers linked their
      hesitation to start a conversation about depression with stigma. They highlighted
      that mothers were not receptive to discussing depression and accepting a
      referral. It was also revealed that the fragmented primary health care system and
      the lack of collaboration between health and mental health services have resulted
      in an unfavorable situation towards maternal mental health. CONCLUSIONS: Even
      though pediatricians and health visitors are aware about maternal depression and
      the importance of maternal mental health, however they fail to implement
      detection and management practices successfully. The inefficiently decentralized
      psychiatric services but also stigmatization and misconceptions about maternal
      depression have impeded the integration of maternal mental health into primary
      care and prevent pediatric primary health care providers from implementing
      detection and management practices.

PMID- 24725739
TI  - An 18F-FDG PET study of cervical muscle in parkinsonian anterocollis.
AB  - The underlying etiology of parkinsonian anterocollis has been the subject of
      recent debate. The purpose of this study is to test the hypothesis that
      anterocollis in parkinsonian syndromes is associated with dystonia of the deep
      cervical flexors (longus colli and capitis). Eight patients with anterocollis,
      six in the setting of parkinsonism and two primary cervical dystonia control
      subjects with anterocollis underwent prospective structured clinical evaluations
      (interview, examination and rating scales), systematic electromyography of the
      cervical extensor musculature and (18)F-FDG PET/CT studies of cervical muscles to
      examine evidence of hypermetabolism or overactivity of deep cervical flexors.
      Subjects with parkinsonian anterocollis were found to have hypermetabolism of the
      extensor and sub-occipital muscles but not in the cervical flexors (superficial
      or deep). EMG abnormalities were observed in all evaluated patients, but only one
      patient was definitely myopathic. Meanwhile, both dystonia controls exhibited
      hypermetabolism of cervical flexors (including the longus colli). In conclusion,
      we were able to demonstrate hypermetabolism of superficial and deep cervical
      flexors with muscle (18)F-FDG PET/CT in dystonic anterocollis patients, but not
      in parkinsonian anterocollis patients. The hypermetabolic changes seen in
      parkinsonian anterocollis patients in posterior muscles may be compensatory.
      Alternative explanations for anterocollis include myopathy of the cervical
      extensors, or unbalanced rigidity of the cervical flexors, but this remains to be
      proven. 

PMID- 24725740
TI  - Glibenclamide treatment modulates the expression and localization of myosin-IIB
      in diabetic rat brain.
AB  - BACKGROUND: Myosin-IIB is a non-muscle isoform in the brain with increased
      expression in the brains of diabetic rats. Chronic hyperglycemia caused by
      diabetes can impair learning and memory. Oral hypoglycemic agents such as
      glibenclamide have been used to control hyperglycemia. We report changes in the
      expression and distribution of myosin-IIB in the frontal cortex and hippocampus
      of diabetic rats treated with glibenclamide. METHODS: The brains were removed
      after 43 days of treatment with glibenclamide (6 mg/kg bw orally), homogenized
      and analyzed by Western blotting, qRT-PCR and immunohistochemistry. RESULTS:
      Myosin-IIB expression increased in the brains of diabetic rats. However, protein
      expression returned to control levels when treated with glibenclamide. In
      addition, the expression of MYH10 gene encoding non-muscle myosin heavy chain-B
      decreased in diabetic rats treated with glibenclamide. Moreover, we found weak
      myosin-IIB labeling in the hippocampus and frontal cortex of rats treated with
      glibenclamide. Therefore, the expression of myosin-IIB is affected by diabetes
      mellitus and may be modulated by glibenclamide treatment in rats. Structural
      changes in the hippocampus and prefrontal cortex are reversible, and
      glibenclamide treatment may reduce the patho-physiological changes in the brain.
      CONCLUSIONS: Our findings can contribute to the understanding of the regulation
      of myosins in the brains of diabetic rats.

PMID- 24725741
TI  - [Homeopathic medications and products: everything in its place].

PMID- 24725742
TI  - A robust scoring system to evaluate sepsis severity in an animal model.
AB  - BACKGROUND: The lack of a reliable scoring system that predicts the development
      of septic shock and death precludes comparison of disease and/or treatment
      outcomes in animal models of sepsis. We developed a murine sepsis score (MSS)
      that evaluates seven clinical variables, and sought to assess its validity and
      reliability in an experimental mouse model of polymicrobial sepsis. METHODS:
      Stool collected from the cecum of C57BL/6 (B6) mice was dissolved in 0.9% normal
      saline (NS) and filtered, resulting in a fecal solution (FS) which was injected
      intraperitoneally into B6 mice. Disease severity was monitored by MSS during the
      experimental timeline. Blood and tissue samples were harvested for the evaluation
      of inflammatory changes after sepsis induction. The correlation between pro
      inflammatory markers and MSS was assessed by the Spearman rank correlation
      coefficient. RESULTS: Mice injected with FS at a concentration of 90 mg/mL
      developed polymicrobial sepsis with a 75% mortality rate at 24 hours. The MSS was
      highly predictive of sepsis progression and mortality, with excellent
      discriminatory power, high internal consistency (Cronbach alpha coefficient =
      0.92), and excellent inter-rater reliability (intra-class coefficient = 0.96). An
      MSS of 3 had a specificity of 100% for predicting onset of septic shock and death
      within 24 hours. Hepatic dysfunction and systemic pro-inflammatory responses were
      confirmed by biochemical and cytokine analyses where the latter correlated well
      with the MSS. Significant bacterial dissemination was noted in multiple organs.
      Furthermore, the liver, spleen, and intestine demonstrated histopathological
      evidence of injury. CONCLUSIONS: The MSS reliably predicts disease progression
      and mortality in an animal model of polymicrobial sepsis. More importantly, it
      may be used to assess and compare outcomes among various experimental models of
      sepsis, and serve as an ethically acceptable alternative to death as an endpoint.

PMID- 24725743
TI  - Speciation of metal(loid)s in environmental samples by X-ray absorption
      spectroscopy: a critical review.
AB  - Element specificity is one of the key factors underlying the widespread use and
      acceptance of X-ray absorption spectroscopy (XAS) as a research tool in the
      environmental and geo-sciences. Independent of physical state (solid, liquid,
      gas), XAS analyses of metal(loid)s in complex environmental matrices over the
      past two decades have provided important information about speciation at
      environmentally relevant interfaces (e.g. solid-liquid) as well as in different
      media: plant tissues, rhizosphere, soils, sediments, ores, mineral process
      tailings, etc. Limited sample preparation requirements, the concomitant ability
      to preserve original physical and chemical states, and independence from
      crystallinity add to the advantages of using XAS in environmental investigations.
      Interpretations of XAS data are founded on sound physical and statistical models
      that can be applied to spectra of reference materials and mixed phases,
      respectively. For spectra collected directly from environmental matrices,
      abstract factor analysis and linear combination fitting provide the means to
      ascertain chemical, bonding, and crystalline states, and to extract quantitative
      information about their distribution within the data set. Through advances in
      optics, detectors, and data processing, X-ray fluorescence microprobes capable of
      focusing X-rays to micro- and nano-meter size have become competitive research
      venues for resolving the complexity of environmental samples at their inherent
      scale. The application of MU-XANES imaging, a new combinatorial approach of X-ray
      fluorescence spectrometry and XANES spectroscopy at the micron scale, is one of
      the latest technological advances allowing for lateral resolution of chemical
      states over wide areas due to vastly improved data processing and detector
      technology. 

PMID- 24725744
TI  - Ultrasensitive electrochemical sensor for p-nitrophenyl organophosphates based on
      ordered mesoporous carbons at low potential without deoxygenization.
AB  - p-Nitrophenyl organophosphates (OPs) including paraoxon, parathion and methyl
      parathion, etc, are highly poisonous OPs, for which sensitive and rapid detection
      method is most needed. In this work, an ultrasensitive electrochemical sensor for
      the determination of p-nitrophenyl OPs was developed based on ordered mesoporous
      carbons (OMCs) modified glassy carbon electrode (GCE) (OMCs/GCE). The
      electrochemical behavior and reaction mechanism of p-nitrophenyl OPs at OMCs/GCE
      was elaborated by taking paraoxon as an example. Experimental conditions such as
      buffer pH, preconcentration potential and time were optimized. By using
      differential pulse voltammetry, the current response of the sensor at -0.085 V
      was linear with concentration within 0.01-1.00 MUM and 1.00-20 MUM paraoxon.
      Similar linear ranges of 0.015-0.5 MUM and 0.5-10 MUM were found for parathion,
      and 0.01-0.5 MUM and 0.5-10 MUM for methyl parathion. The low limits of detection
      were evaluated to be 1.9nM for paraoxon, 3.4 nM for parathion and 2.1 nM for
      methyl parathion (S/N=3). Common interfering species had no interference to the
      detection of p-nitrophenyl OPs. The sensor can be applicable to real samples
      measurement. Therefore, a simple, sensitive, reproducible and cost-effective
      electrochemical sensor was proposed for the fast direct determination of trace p
      nitrophenyl OPs at low potential without deoxygenization.

PMID- 24725745
TI  - Cobalt oxide nanoparticles as a novel high-efficiency fiber coating for solid
      phase microextraction of benzene, toluene, ethylbenzene and xylene from aqueous
      solutions.
AB  - In this work cobalt oxide nanoparticles were introduced for preparation of a
      novel solid phase microextraction (SPME) fiber coating. Chemical bath deposition
      (CBD) technique was used in order for synthesis and immobilization of the Co3O4
      nanomaterials on a Pt wire for fabrication of SPME fiber. The prepared cobalt
      oxide coating was characterized by scanning electron microscopy (SEM) and X-ray
      diffraction (XRD) analysis. The fiber was evaluated for the extraction of
      benzene, toluene, ethylbenzene and xylene (BTEX) in combination with GC-MS. A
      simplex optimization method was used to optimize the factors affecting the
      extraction efficiency. Under optimized conditions, the proposed fiber showed
      extraction efficiencies comparable to those of a commercial polydimethylsiloxane
      (PDMS) fiber toward the BTEX compounds. The repeatability of the fiber and its
      reproducibility, expressed as relative standard deviation (RSD), were lower than
      about 11%. No significant change was observed in the extraction efficiency of the
      new SPME fiber after over 50 extractions. The fiber was successfully applied to
      the determination of BTEX compounds in real samples. The proposed nanostructure
      cobalt oxide fiber is a promising alternative to the commercial fibers as it is
      robust, inexpensive and easily prepared. 

PMID- 24725746
TI  - Methylenedioxy designer drugs: mass spectrometric characterization of their
      glutathione conjugates by means of liquid chromatography-high-resolution mass
      spectrometry/mass spectrometry and studies on their glutathionyl transferase
      inhibition potency.
AB  - Methylenedioxy designer drugs of abuse such as 3,4-methylenedioxymethamphetamine
      (MDMA) can be selectively toxic to serotonergic neurons and glutathione (GSH)
      adducts have been implicated in its neurotoxicity. The catecholic demethylenyl
      metabolites of MDMA, 3,4-dihydroxymethamphetamine and 3,4-dihydroxyamphetamine,
      are metabolically oxidized to the corresponding ortho-quinones, which are highly
      reactive intermediates. These intermediates can then be conjugated with GSH
      preventing cellular damage. Furthermore, glutathionyl transferase (GST) activity
      was described to be irreversibly inhibited by the catechols dopamine, alpha
      methyldopa and their GSH conjugates. Therefore, the aims of the present work were
      the detection and characterization of GSH conjugates of ten methylenedioxy drugs
      of abuse and their phase I metabolites as well as to assess their inhibition
      potency on GST activity. The substrates were incubated using human placental GST
      with or without preincubation by cytochrome P450 enzymes preparations. GST
      inhibition was tested using chlorodinitrobenzene GSH conjugation as marker
      reaction. GSH conjugates were analyzed and characterized using LC-high-resolution
      MS/MS. For confirmation of postulated fragmentation patterns, formation of GSH
      conjugates of selected deuterated analogs (deuterated analogue approach, DAA) of
      the investigated drugs was explored. For the methylenedioxy amphetamines the
      following steps could be identified: conjugation of the parent compounds at
      position 2, 5, 6, of the demethylenyl metabolites at position 2 and 5, and of the
      further deaminated demethylenyl metabolites at position 2. For the beta-keto
      phenylalkylamine and pyrrolidinophenone, conjugation of the demethylenyl
      metabolites and of the deaminated demethylenyl metabolites at position 2 could be
      identified. The DAA allowed the differentiation of the 2 and 5/6 isomers by
      confirmation of the postulated mass spectral fragments. Finally, the tested drugs
      and phase I metabolites showed no inhibition potency on GST activity. 

PMID- 24725747
TI  - Preparation of thin-sections of painting fragments: classical and innovative
      strategies.
AB  - For more than a century, the analyses of painting fragments have been carried out
      mainly through the preparation of thick resin-embedded cross-sections. Taking
      into account the development of innovative micro-analytical imaging techniques,
      alternatives to this standard preparation method are considered. Consequently,
      dedicated efforts are required to develop preparation protocols limiting the
      risks of chemical interferences (solubilisation, reduction/oxidation or other
      reactions) which modify the sample during its preparation, as well as the risks
      of analytical interferences (overlap of detected signals coming from the sample
      and from materials used in the preparation). This study focuses particularly on
      the preparation of thin-sections (1-20 MUm) for single or combined fourier
      transform infrared (FTIR) spectroscopy and X-ray 2D micro-analysis. A few
      strategies specially developed for the MUFTIR analysis of painting cross-sections
      have already been reported and their potential extrapolation to the preparation
      of thin-sections is discussed. In addition, we propose two new specific methods:
      (i) the first is based on a free-embedding approach, ensuring a complete chemical
      and analytical neutrality. It is illustrated through application on polymeric
      design objects corpus; (ii) the second is based on a barrier coating approach
      which strengthens the sample and avoids the penetration of the resin into the
      sample. The barrier coating investigated is a silver chloride salt, an infrared
      transparent material, which remains malleable and soft after pellet compression,
      enabling microtoming. This last method was successfully applied to the
      preparation of a fragment from a gilded Chinese sculpture (15th C.) and was used
      to unravel a unique complex stratigraphy when combining MUFTIR and MUXRF.

PMID- 24725748
TI  - Triazole-based Zn2+-specific molecular marker for fluorescence bioimaging.
AB  - Fluorescence bioimaging potential, both in vitro and in vivo, of a yellow
      emissive triazole-based molecular marker has been investigated and demonstrated.
      Three different kinds of cells, viz Bacillus thuringiensis, Candida albicans, and
      Techoma stans pollen grains were used to investigate the intracellular zinc
      imaging potential of 1 (in vitro studies). Fluorescence imaging of translocation
      of zinc through the stem of small herb, Peperomia pellucida, having transparent
      stem proved in vivo bioimaging capability of 1. This approach will enable in
      screening cell permeability and biostability of a newly developed probe.
      Similarly, the current method for detection and localization of zinc in Gram seed
      sprouts could be an easy and potential alternative of the existing analytical
      methods to investigate the efficiency of various strategies applied for
      increasing zinc-content in cereal crops. The probe-zinc ensemble has efficiently
      been applied for detecting phosphate-based biomolecules. 

PMID- 24725749
TI  - Sampling 4-chlorophenol in water by DGT technique with molecularly imprinted
      polymer as binding agent and nylon membrane as diffusive layer.
AB  - For the first time, a diffusive gradients in thin films (DGT) device using
      molecularly imprinted polymer (MIP) as the binding agent and nylon membrane (NM)
      as the diffusive layer (NM-MIP-DGT) has been developed for sampling 4
      chlorophenol (4-CP) in water. The MIP was prepared by precipitation
      polymerization with methacrylic acid as monomer and ethyleneglycoldimethacrylate
      as cross-linker. The diffusion coefficient of 4-CP through NM was obtained to be
      0.788+/-0.040 MU cm(2) s(-1) by diffusion cell method. The ratio was 1.01+/-0.05
      (mean+/-standard deviation) for the concentration of 4-CP sampled by NM-MIP-DGT
      and analyzed by HPLC method to the total concentration of 4-CP in the synthetic
      solution where free 4-CP species dominated. The results showed that NM-MIP-DGT
      could sample 4-CP in synthetic solution accurately. The performance of NM-MIP-DGT
      for sampling 4-CP was independent of pH in the range of 3-7 and ionic strength in
      the range of 0.0001-0.1 mol L(-1) NaCl solution. The concentration of free form
      of 4-CP sampled by NM-MIP-DGT decreased with the increasing concentration of
      dissolved organic carbon in different water samples due to the electrostatic
      interaction of natural organic compounds with 4-CP. 1.8 mg L(-1) of the free form
      of 4-CP was determined by HPLC which was sampled by NM-MIP-DGT in an intermediate
      untreated industrial effluent. The NM-MIP-DGT can be a potential passive tool for
      sampling the free form of 4-CP in water.

PMID- 24725751
TI  - A case of osmotic demyelination syndrome occurred after the correction of severe
      hyponatraemia in hyperemesis gravidarum.
AB  - BACKGROUND: Osmotic demyelination syndrome (ODS) may be observed as a result of a
      rapid change in serum osmolarity, such as that induced by an overly rapid
      correction of serum sodium levels in hyponatraemic patients. CASE PRESENTATION:
      We describe the case of a 21-year-old woman who was hospitalized at week 10 of
      gestation because of severe hyperemesis. At admission the patient appeared
      restless and confused and severe hyponatraemia (serum sodium 107 mmol/L) and
      hypokalemia (serum potassium 1.1 mmol/L) were detected. Active and simultaneous
      correction of these imbalances led to an overly rapid increase of serum sodium
      levels (17 mmol/L in the first 24 hours). Isotonic saline solution was stopped
      and replaced by 5% dextrose solution infusion. However, the neurological
      alterations worsened and the radiological features were consistent with the
      diagnosis of extra-pontine ODS. Steroids were administered intravenously with
      progressive improvement of biochemical and clinical abnormalities. At the time of
      discharge, 20 days later, the patient was able to walk and eat autonomously with
      only minimal external support. CONCLUSIONS: This report illustrates an unusual
      case of ODS, occurred after an excessive rate of correction of hyponatraemia
      obtained with isotonic saline infusion. Hypokaliemia and its active correction
      very likely played a crucial role in facilitating the onset of ODS. This
      interesting aspect will be explained in detail in the article. A more cautious
      and thoughtful correction of electrolyte alterations, would have probably
      prevented the onset of ODS in this patient. Physicians should be aware of the
      possibly fatal consequences that an exceedingly rapid change of serum osmolarity
      may have and should strictly follow the known safety measures in order to prevent
      it to occur.

PMID- 24725750
TI  - Monitoring prevention or emergence of HIV drug resistance: results of a
      population-based foundational survey of early warning indicators in mainland
      Tanzania.
AB  - BACKGROUND: In Tanzania, routine individual-level testing for HIV drug resistance
      (HIVDR) using laboratory genotyping and phenotyping is not feasible due to
      resource constraints. To monitor the prevention or emergence of HIVDR at a
      population level, WHO developed generic strategies to be adapted by countries,
      which include a set of early warning indicators (EWIs). METHODS: To establish a
      baseline of EWIs, we conducted a retrospective longitudinal survey of 35
      purposively sampled care and treatment clinics in 17 regions of mainland
      Tanzania. We extracted data relevant for four EWIs (ART prescribing practices,
      patients lost to follow-up 12 months after ART initiation, retention on first
      line ART at 12 months, and ART clinic appointment keeping in the first 12 months)
      from the patient monitoring system on patients who initiated ART at each
      respective facility in 2010. We uploaded patient information into WHO HIVResNet
      excel-based tool to compute national and facility averages of the EWIs and tested
      for associations between various programmatic factors and EWI performance using
      Fisher's Exact Test. RESULTS: All sampled facilities met the WHO EWI target
      (100%) for ART prescribing practices. However, the national averages for patients
      lost to follow-up 12 months after ART initiation, retention on first-line ART at
      12 months, and ART clinic appointment keeping in the first 12 months fell short,
      at 26%, 54% and 38%, respectively, compared to the WHO targets <= 20%, >= 70%,
      and >= 80%. Clinics with fewer patients lost to follow-up 12 months after ART
      initiation and more patients retained on first-line-ART at 12 months were more
      likely to have their patients spend the longest time in the facility (including
      wait-time and time with providers), (p = 0.011 and 0.007, respectively).
      CONCLUSION: Tanzania performed very well in EWI 1a, ART prescribing practices.
      However, its performance in other three EWIs was far below the WHO targets. This
      study provides a baseline for future monitoring of EWIs in Tanzania and
      highlights areas for improvement in the management of ART patients in order not
      only to prevent emergence of HIVDR due to programmatic factors, but also to
      improve the quality of life for ART patients.

PMID- 24725752
TI  - Fatigue and serum testosterone in obstructive sleep apnea patients.
AB  - INTRODUCTION: Obstructive sleep apnea (OSA)-related fatigue is a common
      understudied symptom. Fatigue is associated with low serum testosterone level in
      non-OSA patients. No data are available about this association in OSA patients.
      OBJECTIVES: To investigate in adult obese males affected by OSA, the relationship
      between fatigue and serum testosterone in order to identify predictors for OSA
      related fatigue. METHODS: Fifteen OSA patients and 15 control subjects
      participated. The parameters analyzed were serum testosterone morning
      concentration, polysomnography parameters, daytime sleepiness (Epworth Sleepiness
      Scale) and fatigue (Multidimensional Fatigue Inventory). Regression test was
      applied in order to show predictors of fatigue. Kruskal-Wallis test followed by
      post-hoc analysis was performed to test for differences between controls and OSA
      subgroups for testosterone, fatigue components and sleepiness. RESULTS: Mean
      testosterone level was 3.55 +/- 0.7 ng/mL in the OSA group, significantly lower
      than in controls (4.26 +/- 1.1 ng/mL, P = 0.049). An inverse correlation was
      found between testosterone and fatigue scores (P < 0.01). Furthermore, a
      statistically significant difference was found between the control group and the
      severe OSA subgroup for general fatigue, physical fatigue, reduced activity and
      mental fatigue. However, no significant differences were found between controls
      and mild OSA. Among all variables, testosterone was the only independent
      significant predictor of physical fatigue (t = -2.56, P = 0.033, R = 0.978, R(2) 
      = 0.958) and reduced activity (t = -4.41, P = 0.002, R = 0.966, R(2)  = 0.934) in
      the OSA patients. CONCLUSIONS: OSA-related fatigue was strongly associated with
      serum testosterone, together with OSA severity.

PMID- 24725753
TI  - Mapping dynamical mechanical properties of osteonal bone by scanning acoustic
      microscopy in time-of-flight mode.
AB  - An important determinant of mechanical properties of bone is Young's modulus and
      its variation in individual osteons of cortical bone tissue. Its mechanical
      behavior also depends on deformation rate owing to its visco- or poroelastic
      properties. We developed a method to measure dynamical mechanical properties of
      bulk bone tissue at osteonal level based on scanning acoustic microscopy (SAM)
      using time-of-flight (TOF) measurements in combination with quantitative
      backscattered electron imaging (qBEI). SAM-TOF yields local sound velocities and
      qBEI corresponding material densities together providing elastic properties.
      Osteons (n=55) were measured in three human femoral diaphyseal ground bone
      sections (~ 30 um in thickness). In addition, subchondral bone and mineralized
      articular cartilage were investigated. The mean mineral contents, the mean sound
      velocities, and the mean elastic modulus of the osteons ranged from 20 to 26 wt%,
      from 3,819 to 5,260 m/s, and from 21 to 44 GPa, respectively. There was a strong
      positive correlation between material density and sound velocity (Pearson's
      r=0.701; p<0.0001) of the osteons. Sound velocities between cartilage and bone
      was similar, though material density was higher in cartilage (+4.46%, p<0.0001).
      These results demonstrate the power of SAM-TOF to estimate dynamic mechanical
      properties of the bone materials at the osteonal level.

PMID- 24725754
TI  - Is serum uric acid related to non-motor symptoms in de-novo Parkinson's disease
      patients?
AB  - BACKGROUND: Low serum uric acid (UA) has been consistently shown to be associated
      with increased risk of Parkinson's disease (PD), and to predict faster motor and
      cognitive decline in established PD. The aim of the present study is to evaluate
      the relationship between serum UA and non-motor symptoms (NMS) in de novo PD.
      METHODS: Serum UA was measured in consecutively recruited, early drug-naive PD
      patients. Exclusion criteria were: treatment with UA modifying drugs; current
      smoking status; metabolic or cardiac morbidity. All patients completed the NMS
      Questionnaire (NMSQuest). The relationship between UA levels and NMSQuest domains
      was explored by logistic regression, subsequently adjusted for age, gender,
      disease duration (months since reported motor onset) UPDRS part III, H&Y scale,
      and MMSE. Regression analysis studied the overall relationship between UA levels
      and total NMS score, and was subsequently adjusted for age, gender, disease
      duration UPDRS part III, H&Y scale and MMSE. RESULTS: Eighty PD patients were
      recruited. At logistic regression, higher UA levels were related to lower
      involvement of Attention/Memory (p = 0.004), Cardiovascular (0.009) and Sleep (p
      = 0.028) domains of NMSQuest. UA levels showed a significant negative correlation
      with total NMSQuest score at regression analysis (p = 0.001; Adjusted R-squared =
      0.319). DISCUSSION: The present study investigated, for the first time, the
      relationship between NMSQuest and UA in de novo PD. Lower UA was related to
      higher NMSQuest total score and in particular to Attention/Memory, Cardiovascular
      and Sleep domains. Thus, UA seems to be a major candidate to be a valuable
      biomarker of such early features of PD as NMS.

PMID- 24725755
TI  - Exploring young adults' contraceptive knowledge and attitudes: disparities by
      race/ethnicity and age.
AB  - BACKGROUND: Half of pregnancies in the United States are unintended, with the
      highest proportions occurring among Blacks, Hispanics, and teenagers.
      Understanding differences in knowledge and attitudes about contraception by
      race/ethnicity and age can improve efforts to reduce disparities in unintended
      pregnancy. METHODS: This analysis used data from the 897 female respondents in
      National Survey of Reproductive and Contraceptive Knowledge, a survey exploring
      young adults' knowledge and attitudes about contraception and pregnancy.
      Bivariate and multivariate logistic regression analyses were used to assess
      racial/ethnic and age group differences in knowledge and attitudes about
      contraceptives. FINDINGS: Hispanics and teenagers (aged 18-19) had lower
      awareness of available contraceptive methods, and lower knowledge about
      individual methods compared with White women and young adults (age 20-29). For
      example, Hispanics (74%) and teenagers (77%) were less likely to have heard of
      the intrauterine device (IUD) than were White women (90%) and young adults (90%),
      and were less likely to know that a woman experiencing side effects could switch
      brands of oral contraceptive pills (72% of Hispanics vs. 86% of White women; 76%
      of teenagers vs. 90% of young adults). Hispanics born outside the United States
      had lower knowledge about contraceptives than U.S.-born Hispanics. For example,
      foreign-born Hispanics were less likely than U.S.-born Hispanics to have heard of
      the IUD (59% vs. 82%) or the vaginal ring (55% vs. 95%). CONCLUSIONS: Lower
      contraceptive knowledge among teenagers and Hispanics, particularly immigrants,
      suggests the importance of disseminating family planning information to these
      women as one means to address disparities in unintended pregnancy.

PMID- 24725757
TI  - Knowledge and perceptions of breast health among free clinic patients.
AB  - BACKGROUND: Breast cancer is a significant women's health problem in the United
      States. However, critical information on specific populations is still lacking.
      In particular, it is not well known how free clinic patients perceive breast
      health. The purpose of this study was to assess knowledge and perceptions of
      breast health among uninsured women utilizing a free clinic that serves as a
      safety net for the underserved. METHODS: A self-administrated survey that
      included knowledge and perceptions of breast health was conducted for female free
      clinic patients aged 40 or older in fall 2012. There were 146 participants. The
      participants were classified into three groups for comparison; U.S. citizen
      English speakers, non-U.S. citizen English speakers, and Spanish speakers.
      RESULTS: Spanish speakers had the highest average score on the knowledge of
      breast health, whereas the non-U.S. citizen English speakers had the lowest
      average score. Free clinic patients may consider breast health screening if
      recommended by health care providers. The non-U.S. citizen English speakers and
      Spanish speakers were more likely to have negative perceptions of breast health
      compared with the U.S. citizen English speakers. CONCLUSIONS: Promoting knowledge
      about breast health is important for free clinics. Recommendation by a health
      care provider is a key to increasing attendance at health education programs and
      breast health screening. Non-U.S. citizens and non-English speakers would need
      culturally competent interventions. Free clinics have limited human and financial
      resources. Such characteristics of free clinics should be considered for practice
      implementations.

PMID- 24725756
TI  - Mammographic breast density as a risk factor for breast cancer: awareness in a
      recently screened clinical sample.
AB  - BACKGROUND: Breast density is an established, independent risk factor for breast
      cancer. Despite this, density has not been included in standard risk models or
      routinely disclosed to patients. However, this is changing in the face of legal
      mandates and advocacy efforts. Little information exists regarding women's
      awareness of density as a risk factor, their personal risk, and risk management
      options. METHODS: We assessed awareness of density as a risk factor and whether
      sociodemographic variables, breast cancer risk factors. and perceived breast
      cancer risk were associated with awareness in 344 women with a recent screening
      mammogram at a tertiary care center. FINDINGS: Overall, 62% of women had heard
      about density as a risk factor and 33% had spoken to a provider about breast
      density. Of the sample, 18% reported that their provider indicated that they had
      high breast density. Awareness of density as a risk factor was greater among
      White women and those with other breast cancer risk factors. CONCLUSION: Our
      results suggest that although a growing number of women are aware of breast
      density as a risk factor, this awareness varies. Growing mandates for disclosure
      suggest the need for patient education interventions for women at increased risk
      for the disease and to ensure all women are equally aware of their risks.

PMID- 24725758
TI  - Altered vitamin D status in liver tissue and blood plasma from Greenland sledge
      dogs (Canis familiaris) dietary exposed to organohalogen contaminated minke whale
      (Balaenoptera acuterostrata) blubber.
AB  - This study compared vitamin D3 (vitD3) and 25-OH vitamin D3 (25OHD3) status in
      Greenland sledge dogs (Canis familiaris) given either minke whale (Balaenoptera
      acuterostrata) blubber high in organohalogen contaminants (OHCs) or clean porcine
      (Suis scrofa) fat for up to 636 days. A group of six exposed and six control
      sister bitches (maternal generation) and their three exposed and four control
      pups, respectively, were daily fed 112g whale blubber (193ug ?PCB/day) or porcine
      fat (0.17ug ?PCB/day). Mean level of ?PCB in adipose tissue of exposed bitches
      and their pups was 3106 and 2670ng/g lw, respectively, which was significantly
      higher than the mean concentration of 53ng/g lw for all controls (p<0.001). The
      vitamin analyses showed that 25OHD3 in liver of maternal exposed bitches were
      significantly lower than in controls (p=0.004) while vitD3 was significantly
      highest in liver of exposed pups (p<0.003). Regarding blood plasma
      concentrations, exposed F generation pups had significantly higher concentrations
      of 25OHD3 than controls (p=0.009). Correlation analyses showed that blood 25OHD3
      decreased significantly with increased adipose tissue concentrations of ?PCB in
      exposed dogs (R(2)=0.64, p=0.005) and a similar trend was found for liver 25OHD3
      (R(2)=0.32, p=0.08). The results indicate that the homeostasis and metabolism of
      vitamin D compounds may respond differently to the dietary composition of fatty
      acids and OHC exposure. It is unknown if the lower level of 25OHD3 in the liver
      of exposed dogs would have any negative effects on immunity and reproduction and
      more focus should be conducted on this compound in Arctic wildlife. 

PMID- 24725759
TI  - Measuring the impact of spatial network layout on community social cohesion: a
      cross-sectional study.
AB  - BACKGROUND: There is now a substantial body of research suggesting that social
      cohesion, a collective characteristic measured by the levels of trust,
      reciprocity and formation of strong social bonds within communities, is an
      important factor in determining health. Of particular interest is the extent to
      which factors in the built environment facilitate, or impede, the development of
      social bonds. Severance is a characteristic of physical environments which is
      hypothesized to inhibit cohesion. In the current study we test a number of
      characteristics of spatial networks which could be hypothesized to relate either
      to severance, or directly to community cohesion. Particular focus is given to our
      most promising variable for further analysis (Convex Hull Maximum Radius 600 m).
      METHODS: In the current study we analysed social cohesion as measured at
      Enumeration District level, aggregated from a survey of 10,892 individuals aged
      18 to 74 years in the Caerphilly Health and Social Needs Cohort Study, 2001. In a
      data mining process we test 16 network variables on multiple scales. The variable
      showing the most promise is validated in a test on an independent data set. We
      then conduct a multivariate regression also including Townsend deprivation scores
      and urban/rural status as predictor variables for social cohesion. RESULTS: We
      find convex hull maximum radius at a 600 m scale to have a small but highly
      significant correlation with social cohesion on both data sets. Deprivation has a
      stronger effect. Splitting the analysis by tertile of deprivation, we find that
      the effect of severance as measured by this variable is strongest in the most
      deprived areas. A range of spatial scales are tested, with the strongest effects
      being observed at scales that match typical walking distances. CONCLUSION: We
      conclude that physical connectivity as measured in this paper has a significant
      effect on social cohesion, and that our measure is unlikely to proxy either
      deprivation or the urban/rural status of communities. Possible mechanisms for the
      effect include intrinsic navigability of areas, and the existence of a focal
      route on which people can meet on foot. Further investigation may lead to much
      stronger predictive models of social cohesion.

PMID- 24725760
TI  - Clinical role of pathological downgrading after radical prostatectomy in patients
      with biopsy confirmed Gleason score 3 + 4 prostate cancer.
AB  - OBJECTIVE: To identify preoperative factors predicting Gleason score downgrading
      after radical prostatectomy (RP) in patients with biopsy Gleason score 3+4
      prostate cancer and to determine if prediction of downgrading can identify
      potential candidates for active surveillance (AS). PATIENTS AND METHODS: We
      identified 1317 patients with biopsy Gleason score 3+4 prostate cancers who
      underwent RP at the Memorial Sloan-Kettering Cancer Center between 2005 and 2013.
      Several preoperative and biopsy characteristics were evaluated by forward
      selection regression, and selected predictors of downgrading were analysed by
      multivariable logistic regression. Decision curve analysis was used to evaluate
      the clinical utility of the multivariate model. RESULTS: Gleason score was
      downgraded after RP in 115 patients (9%). We developed a multivariable model
      using age, prostate-specific antigen density, percentage of positive cores with
      Gleason pattern 4 cancer out of all cores taken, and maximum percentage of cancer
      involvement within a positive core with Gleason pattern 4 cancer. The area under
      the curve for this model was 0.75 after 10-fold cross validation. However,
      decision curve analysis revealed that the model was not clinically helpful in
      identifying patients who will downgrade at RP for the purpose of reassigning them
      to AS. CONCLUSION: While patients with pathological Gleason score 3 + 3 with
      tertiary Gleason pattern <=4 at RP in patients with biopsy Gleason score 3 + 4
      prostate cancer may be potential candidates for AS, decision curve analysis
      showed limited utility of our model to identify such men. Future study is needed
      to identify new predictors to help identify potential candidates for AS among
      patients with biopsy confirmed Gleason score 3 + 4 prostate cancer.

PMID- 24725761
TI  - Usefulness of automated assessment of nuclear cardiology for prediction of major
      cardiac events in Japanese patients with known or suspected coronary artery
      disease: comparison with conventional visual assessment in a large-scale
      prognostic study.
AB  - BACKGROUND: There are no reports indicating that automated quantification with a
      total perfusion deficit (TPD) is used to predict future cardiac events in
      Japanese patients. We, therefore, aimed to determine the prognostic value of the
      automated assessment with the TPD for risk stratification of major cardiac events
      (MCEs) in Japanese patients with known or suspected coronary artery disease
      (CAD). METHODS: We retrospectively investigated 2848 patients who underwent rest
      (201)Tl and stress (99m)Tc-tetrofosmin myocardial perfusion single photon
      emission computed tomography (SPECT) between October 2004 and March 2008. The
      follow-up period was 25.8 +/- 11.0 months. The TPD was automatically derived from
      the SPECT image through the QPS software with the Japanese normal database.
      Twenty segments of SPECT images were analyzed with the 5-point visual scoring
      model to estimate summed scores. The endpoint of the follow-up was the occurrence
      of MCEs within 1 year after the SPECT, which were identified with medical records
      or responses to a posted questionnaire. RESULTS: During the first year of the
      follow-up, 62 patients had MCEs, which comprised cardiac death (n = 30), non
      fatal myocardial infarction (n = 13), and unstable angina pectoris (n = 19). The
      MCE rates positively correlated with the stress TPD and the summed stress score.
      Sensitivity of the automated quantification with the TPD for detection of the
      MCEs was high and similar to that of the visual semi-quantification. Multivariate
      Cox regression analysis indicated that significant independent predictors for the
      MCEs were an estimated glomerular filtration rate and the ischemic variables both
      in the automated quantification and visual semi-quantification. CONCLUSION: The
      automated quantification with the TPD is useful for prognostic risk
      stratification of MCEs in Japanese patients with known or suspected CAD. Its
      predictive power is similar to that of the visual semi-quantification by expert
      interpreters.

PMID- 24725762
TI  - Author's reply: To PMID 23618914.

PMID- 24725763
TI  - Rationale and design of a randomized clinical study to investigate the effect of
      ezetimibe, a cholesterol absorption inhibitor, on the regression of intracoronary
      plaque evaluated by non-obstructive angioscopy and ultrasound: The ZIPANGU study.
AB  - BACKGROUND AND PURPOSE: It is well recognized that low-density lipoprotein
      cholesterol (LDL-C)-lowering therapy is effective for primary and secondary
      prevention of cerebrovascular/cardiovascular disease. Ezetimibe, an inhibitor of
      the Niemann-Pick C1-Like 1 cholesterol transporter, is a relatively new drug for
      LDL-C-lowering therapy in addition to statins. However, comparison between an
      aggressive LDL-C-lowering therapy with a combination of statin and ezetimibe
      versus a standard LDL-C-lowering therapy with statin alone is still unclear in
      terms of their effects on stabilization and volume regression of coronary plaque.
      The ZIPANGU (Ezetimibe clinical investigation for the regression of intracoronary
      plaque evaluated by angioscopy and ultrasound) study is aimed at comparing these
      two types of therapy based on indices of plaque characteristics using non
      obstructive coronary angioscopy and intravascular ultrasound. METHODS: The study
      is a multi-center, prospective, randomized, open-label, blinded-endpoint trial.
      Through a centralized enrollment method, patients will be allocated to either
      monotherapy with atorvastatin alone or to combination therapy with atorvastatin
      (maximum: 20mg/day) and ezetimibe (10mg/day). The target LDL-C level will be
      <100mg/dL for the monotherapy group and <70mg/dL for the combination therapy
      group. At the baseline and the follow-up period of 9 months, non-obstructive
      coronary angioscopy and intravascular ultrasound will be performed to compare the
      changes in plaque color and volume between the two groups. CONCLUSIONS: The
      ZIPANGU study will clarify whether combination therapy with statins and ezetimibe
      is better for stabilizing coronary plaque as secondary prevention than
      monotherapy by statins alone. The study will give new insights into lipid
      lowering guidelines in Japan.

PMID- 24725764
TI  - A quantitative analysis of gait patterns in vestibular neuritis patients using
      gyroscope sensor and a continuous walking protocol.
AB  - BACKGROUND: Locomotion involves an integration of vision, proprioception, and
      vestibular information. The parieto-insular vestibular cortex is known to affect
      the supra-spinal rhythm generators, and the vestibular system regulates anti
      gravity muscle tone of the lower leg in the same side to maintain an upright
      posture through the extra-pyramidal track. To demonstrate the relationship
      between locomotion and vestibular function, we evaluated the differences in gait
      patterns between vestibular neuritis (VN) patients and normal subjects using a
      gyroscope sensor and long-way walking protocol. METHODS: Gyroscope sensors were
      attached to both shanks of healthy controls (n=10) and age-matched VN patients (n
      = 10). We then asked the participants to walk 88.8 m along a corridor. Through
      the summation of gait cycle data, we measured gait frequency (Hz), normalized
      angular velocity (NAV) of each axis for legs, maximum and minimum NAV, up-slope
      and down-slope of NAV in swing phase, stride-swing-stance time (s), and stance to
      stride ratio (%). RESULTS: The most dominant walking frequency in the VN group
      was not different compared to normal control. The NAVs of z-axis (pitch motion)
      were significantly larger than the others (x-, y-axis) and the values in VN
      patients tended to decrease in both legs and the difference of NAV between both
      group was significant in the ipsi-lesion side in the VN group only (p=0.03).
      Additionally, the gait velocity of these individuals was decreased relatively to
      controls (1.11 +/- 0.120 and 0.84 +/- 0.061 m/s in control and VN group
      respectively, p<0.01), which seems to be related to the significantly increased
      stance and stride time of the ipsi-lesion side. Moreover, in the VN group, the
      maximum NAV of the lesion side was less, and the minimum one was higher than
      control group. Furthermore, the down-slope and up-slope of NAV decreased on the
      impaired side. CONCLUSION: The walking pattern of VN patients was highly phase
      dependent, and NAV of pitch motion was significantly decreased in the ipsi-lesion
      side. The change of gait rhythm, stance and stride time, and maximum/minimum NAV
      of the ipsi-lesion side were characteristics of individuals with VN.

PMID- 24725765
TI  - Understanding the acceptability of e-mental health--attitudes and expectations
      towards computerised self-help treatments for mental health problems.
AB  - BACKGROUND: E-mental health and m-mental health include the use of technology in
      the prevention, treatment and aftercare of mental health problems. With the
      economical pressure on mental health services increasing, e-mental health and m
      mental health could bridge treatment gaps, reduce waiting times for patients and
      deliver interventions at lower costs. However, despite the existence of numerous
      effective interventions, the transition of computerised interventions into care
      is slow. The aim of the present study was to investigate the acceptability of e
      mental health and m-mental health in the general population. METHODS: An advisory
      group of service users identified dimensions that potentially influence an
      individual's decision to engage with a particular treatment for mental health
      problems. A large sample (N = 490) recruited through email, flyers and social
      media was asked to rate the acceptability of different treatment options for
      mental health problems on these domains. Results were analysed using repeated
      measures MANOVA. RESULTS: Participants rated the perceived helpfulness of an
      intervention, the ability to motivate users, intervention credibility, and
      immediate access without waiting time as most important dimensions with regard to
      engaging with a treatment for mental health problems. Participants expected face
      to-face therapy to meet their needs on most of these dimensions. Computerised
      treatments and smartphone applications for mental health were reported to not
      meet participants' expectations on most domains. However, these interventions
      scored higher than face-to-face treatments on domains associated with the
      convenience of access. Overall, participants reported a very low likelihood of
      using computerised treatments for mental health in the future. CONCLUSIONS:
      Individuals in this study expressed negative views about computerised self-help
      intervention and low likelihood of use in the future. To improve the
      implementation and uptake, policy makers need to improve the public perception of
      such interventions.

PMID- 24725766
TI  - National prescribing trends for heart failure medications in children.
AB  - BACKGROUND: The treatment of acute decompensated heart failure (ADHF) in adults
      has changed considerably over the past decade, and these changes have coincided
      with a reduction in inpatient mortality. At this time, national trends in
      medication prescribing among children hospitalized with ADHF are unknown.
      METHODS: The Pediatric Health Information System (PHIS) database was queried to
      identify all patients <=21 years of age who were admitted from 2001 to 2010 with
      ADHF and a diagnosis of cardiomyopathy. Patients were excluded for potential
      infectious or inflammatory etiologies of heart failure, congenital heart disease,
      cardiovascular surgery, acute heart transplant rejection, or isolated diastolic
      dysfunction. Only the index admission was used, and descriptive statistical
      methods were employed. RESULTS: A total of 1773 patients (55.8% male) met study
      criteria (mortality 6.9%). Median length of stay was 9 days (IQR 4-16 days).
      Vasopressor or inotropic agents were used in 63.6% of patients (milrinone in
      82.9% of these) and diuretics in 90.1% (furosemide in 98.4% of these). At
      discharge, a beta-blocker was prescribed in 36.8% of patients (carvedilol in
      77.1% of these), and an angiotensin-converting enzyme (ACE) inhibitor was
      prescribed in 69.6% (enalapril in 59.9% of these). A wide variability in
      prescribing practices over time and by pediatric hospital was noted, along with a
      trend for decreased inotrope use and an increase in beta-blocker discharge
      prescribing. CONCLUSIONS: This is the first national evaluation of prescribing
      trends in pediatric ADHF medication. A large degree of variability in medication
      use for ADHF and low rates of beta-blocker and ACE inhibitor use at discharge
      were identified.

PMID- 24725767
TI  - Cytosolic chloride ion is a key factor in lysosomal acidification and function of
      autophagy in human gastric cancer cell.
AB  - The purpose of the present study was to clarify roles of cytosolic chloride ion
      (Cl(-) ) in regulation of lysosomal acidification [intra-lysosomal pH (pHlys )]
      and autophagy function in human gastric cancer cell line (MKN28). The MKN28 cells
      cultured under a low Cl(-) condition elevated pHlys and reduced the intra
      lysosomal Cl(-) concentration ([Cl(-) ]lys ) via reduction of cytosolic Cl(-)
      concentration ([Cl(-) ]c ), showing abnormal accumulation of LC3II and p62
      participating in autophagy function (dysfunction of autophagy) accompanied by
      inhibition of cell proliferation via G0 /G1 arrest without induction of
      apoptosis. We also studied effects of direct modification of H(+) transport on
      lysosomal acidification and autophagy. Application of bafilomycin A1 (an
      inhibitor of V-type H(+) -ATPase) or ethyl isopropyl amiloride [EIPA; an
      inhibitor of Na(+) /H(+) exchanger (NHE)] elevated pHlys and decreased [Cl(-)
      ]lys associated with inhibition of cell proliferation via induction of G0 /G1
      arrest similar to the culture under a low Cl(-) condition. However, unlike low
      Cl(-) condition, application of the compound, bafilomycin A1 or EIPA, induced
      apoptosis associated with increases in caspase 3 and 9 without large reduction in
      [Cl(-) ]c compared with low Cl(-) condition. These observations suggest that the
      lowered [Cl(-) ]c primarily causes dysfunction of autophagy without apoptosis via
      dysfunction of lysosome induced by disturbance of intra-lysosomal acidification.
      This is the first study showing that cytosolic Cl(-) is a key factor of lysosome
      acidification and autophagy. 

PMID- 24725768
TI  - BAYSIC: a Bayesian method for combining sets of genome variants with improved
      specificity and sensitivity.
AB  - BACKGROUND: Accurate genomic variant detection is an essential step in gleaning
      medically useful information from genome data. However, low concordance among
      variant-calling methods reduces confidence in the clinical validity of whole
      genome and exome sequence data, and confounds downstream analysis for
      applications in genome medicine.Here we describe BAYSIC (BAYeSian Integrated
      Caller), which combines SNP variant calls produced by different methods (e.g.
      GATK, FreeBayes, Atlas, SamTools, etc.) into a more accurate set of variant
      calls. BAYSIC differs from majority voting, consensus or other ad hoc
      intersection-based schemes for combining sets of genome variant calls. Unlike
      other classification methods, the underlying BAYSIC model does not require
      training using a "gold standard" of true positives. Rather, with each new
      dataset, BAYSIC performs an unsupervised, fully Bayesian latent class analysis to
      estimate false positive and false negative error rates for each input method. The
      user specifies a posterior probability threshold according to the user's
      tolerance for false positive and false negative errors; lowering the posterior
      probability threshold allows the user to trade specificity for sensitivity while
      raising the threshold increases specificity in exchange for sensitivity. RESULTS:
      We assessed the performance of BAYSIC in comparison to other variant detection
      methods using ten low coverage (~5X) samples from The 1000 Genomes Project, a
      tumor/normal exome pair (40X), and exome sequences (40X) from positive control
      samples previously identified to contain clinically relevant SNPs. We
      demonstrated BAYSIC's superior variant-calling accuracy, both for somatic
      mutation detection and germline variant detection. CONCLUSIONS: BAYSIC provides a
      method for combining sets of SNP variant calls produced by different variant
      calling programs. The integrated set of SNP variant calls produced by BAYSIC
      improves the sensitivity and specificity of the variant calls used as input. In
      addition to combining sets of germline variants, BAYSIC can also be used to
      combine sets of somatic mutations detected in the context of tumor/normal
      sequencing experiments.

PMID- 24725769
TI  - Iatrogenic innominate arteriovenous fistula repaired with the stent-graft.

PMID- 24725771
TI  - Tracheal diverticulum: an atypical presentation.

PMID- 24725770
TI  - Insurance status predicts acuity of thoracic aortic operations.
AB  - OBJECTIVE: Nonelective case status is the strongest predictor of mortality for
      thoracic aortic operations. We hypothesized that underinsured patients were more
      likely to require nonelective thoracic aortic surgery because of reduced access
      to preventative cardiovascular care and elective surgical services. METHODS:
      Between June 2005 and August 2011, 826 patients were admitted to a single aortic
      referral center and underwent 1 or more thoracic aortic operations. Patients with
      private insurance or Medicare (insured group, n=736; 89%) were compared with
      those with Medicaid or no insurance (underinsured group, n=90; 11%). RESULTS: The
      proportion of patients requiring nonelective surgery was higher for underinsured
      than insured patients (56% vs 26%, P<.0001). Multivariable analysis revealed
      underinsurance to be the strongest independent predictor of nonelective case
      status (odds ratio [OR], 2.67; P<.0001). Preoperative use of lipid-lowering
      medications (OR, 0.63; P<.009) or a history of aortic surgery (OR, 0.48; P<.001)
      was associated with a decreased risk of nonelective operation. However, after
      adjustment for differences in preoperative characteristics and case status,
      underinsurance did not confer an increased risk of procedural morbidity or
      mortality (adjusted OR, 0.94; P=.83) or late death (adjusted hazard ratio, 0.83,
      P=.58) when compared with insured patients. CONCLUSIONS: Underinsured patients
      were at the greatest risk of requiring nonelective thoracic aortic operation,
      possibly because of decreased use of lipid-lowering therapies and aortic
      surveillance. These data imply that greater access to preventative cardiovascular
      care may reduce the need for nonelective thoracic aortic surgery and lead to
      improved survival from thoracic aortic disease.

PMID- 24725772
TI  - Novel repair of a defect in the cervical trachea with a thymus pedicle flap.

PMID- 24725773
TI  - Variability in intraosseous flush practices of emergency physicians.
AB  - OBJECTIVE: Intramedullary pressure changes during intraosseous (IO) procedures
      have been implicated in the intravasation of bone marrow fat and with pain in
      conscious patients. The objective of this study was to demonstrate inter-provider
      variability in pressures generated during initial flush procedures. METHODS: IO
      cannulas were inserted into the proximal tibiae and humeri by study personnel. A
      second cannula was placed in the mid diaphysis of each bone to record
      intramedullary pressures. Fifteen emergency physicians performed 60 flushes in
      random order in two cadavers while flush duration and IO pressure were
      continuously recorded. Providers were blinded to the flush pressures they
      generated and the flush techniques of others. RESULTS: The median IO pressure
      (IOP) generated by providers was 903 mm Hg (range, 83-2941 mm Hg) and the median
      flush duration was 5.2 seconds (range, 1.0-13.4 seconds). Significant differences
      were noted among providers in peak IOP generated (analysis of variance P<.001).
      Providers were consistent in the forces they generated relative to each other. An
      inverse, nonlinear relationship was observed between flush duration and the peak
      IOP generated. Significant differences were noted in intramedullary flush
      pressures at flush sites within cadavers (analysis of variance P: cadaver #1
      P<.001; cadaver #2 P=.012). CONCLUSIONS: The IO compartment pressures generated
      by physicians demonstrated significant interoperator variability with greater
      than 35-fold difference in flush forces, and an inverse relationship between
      intraosseous pressure and flush duration. It may be prudent practice for
      providers to extend the flush over several seconds, thus limiting maximal
      pressures.

PMID- 24725774
TI  - Increased rates of rapid point-of-care HIV testing using patient care technicians
      to perform tests in the ED.
AB  - BACKGROUND: Various emergency department (ED) HIV testing models are reported in
      the literature but may not all be sustainable. We sought to determine whether
      changing an ED rapid HIV testing program from counselor-based to ED technician
      based resulted in more testing. METHODS: We evaluated data from an ED rapid HIV
      testing program. Triage nurses offered testing to patients. In 2009, counselors
      performed rapid testing weekdays from 10:00 am to 6:00 pm. In 2010, ED
      technicians were trained to perform the test and replaced counselors. We compared
      the numbers of tests performed during the same 6-month periods in 2009 and 2010.
      Study personnel abstracted results through medical record review. RESULTS: A
      total of 241 oral tests were performed in 2009 compared with 1483 in 2010,
      representing slightly more than a 6-fold increase. In 2010, there was a steady
      increase in testing month by month. Incorporating patient volume, testing rates
      increased from 1.3% to 8.1%. Oral testing yielded no positive test results in
      2009, but 7 individuals (0.47%) tested newly positive during the testing period
      of 2010. Of those with a documented CD4 count within 100 days of the positive
      result, 4 of 5 had CD4 counts less than 200. CONCLUSIONS: We present a novel
      approach to HIV testing using existing staff within the ED. This new ED
      technician-based model led to large increases in rates of testing.

PMID- 24725775
TI  - The distribution of SNP marker effects for faecal worm egg count in sheep, and
      the feasibility of using these markers to predict genetic merit for resistance to
      worm infections.
AB  - SummaryGenetic resistance to gastrointestinal worms is a complex trait of great
      importance in both livestock and humans. In order to gain insights into the
      genetic architecture of this trait, a mixed breed population of sheep was
      artificially infected with Trichostrongylus colubriformis (n=3326) and then
      Haemonchus contortus (n=2669) to measure faecal worm egg count (WEC). The
      population was genotyped with the Illumina OvineSNP50 BeadChip and 48 640 single
      nucleotide polymorphism (SNP) markers passed the quality controls. An independent
      population of 316 sires of mixed breeds with accurate estimated breeding values
      for WEC were genotyped for the same SNP to assess the results obtained from the
      first population. We used principal components from the genomic relationship
      matrix among genotyped individuals to account for population stratification, and
      a novel approach to directly account for the sampling error associated with each
      SNP marker regression. The largest marker effects were estimated to explain an
      average of 0.48% (T. colubriformis) or 0.08% (H. contortus) of the phenotypic
      variance in WEC. These effects are small but consistent with results from other
      complex traits. We also demonstrated that methods which use all markers
      simultaneously can successfully predict genetic merit for resistance to worms,
      despite the small effects of individual markers. Correlations of genomic
      predictions with breeding values of the industry sires reached a maximum of 0.32.
      We estimate that effective across-breed predictions of genetic merit with multi
      breed populations will require an average marker spacing of approximately 10 kbp.

PMID- 24725776
TI  - Mapping Mendelian traits in asexual progeny using changes in marker allele
      frequency.
AB  - Linkage between markers and genes that affect a phenotype of interest may be
      determined by examining differences in marker allele frequency in the extreme
      progeny of a cross between two inbred lines. This strategy is usually employed
      when pooling is used to reduce genotyping costs. When the cross progeny are
      asexual, the extreme progeny may be selected by multiple generations of asexual
      reproduction and selection. We analyse this method of measuring phenotype in
      asexual progeny and examine the changes in marker allele frequency due to
      selection over many generations. Stochasticity in marker frequency in the
      selected population arises due to the finite initial population size. We derive
      the distribution of marker frequency as a result of selection at a single major
      locus, and show that in order to avoid spurious changes in marker allele
      frequency in the selected population, the initial population size should be in
      the low to mid hundreds.

PMID- 24725777
TI  - Pulmonary immune responses to 2009 pandemic influenza A (H1N1) virus in mice.
AB  - BACKGROUND: Well-characterized mice models will afford a cheaper, easy-handling
      opportunity for a more comprehensive understanding of 2009 influenza A (H1N1)
      virus's pathogenesis potential. We aimed to provide a robust description of
      pulmonary immune responses in the mice infected by the virus. METHODS: BALB/c
      mice were inoculated intranasally with A/Beijing/501/2009(H1N1) (BJ501) and
      A/PR/8/34(H1N1) (PR8) viruses and compared for survival rate, viral replication,
      and kinetics of pulmonary immune responses. RESULTS: BJ501 virus replicated less
      efficiently in the lungs than PR8, and both caused lethal illness in the mice.
      The transient increases of pulmonary TNF-alpha 2 days post infection for BJ501
      and of INF-gamma and IL-10 at 6 days post infection for PR8 were observed. IL-2+
      and IL-4+ secreting cells showed significant increase 12 days post infection,
      while IFN-gamma+, IgG+ and IgA+ secreting cells increased 6 days post infection.
      The different patterns of pulmonary immunological parameters between two viruses
      were at most seen in IL-6, IL-17 secretion and IgG1/IgG2a ratio. CONCLUSIONS: The
      BALB/c mouse is evaluated as a good pathogenic model for studying BJ501 2009 H1N1
      virus. The work provided some basic and detailed data, which might be referred
      when further evaluating innate and adapted pulmonary immune responses and local
      viral load in mice.

PMID- 24725778
TI  - Alterations in platelet count and mean platelet volume as predictors of patient
      outcome in the respiratory intensive care unit.
AB  - INTRODUCTION: Thrombocytopenia is associated with increased mortality in
      intensive care unit (ICU) patients. Mean platelet volume (MPV) reflects platelet
      function and activation. Elevated MPV is associated with poor outcomes and
      increased mortality rate in diseases that are commonly encountered in the
      respiratory ICU. METHODS: We retrospectively enrolled 95 patients who died in the
      ICU (dead group), 80 patients who improved and were transferred from the ICU
      (survived group), and 80 healthy individuals as controls. Laboratory parameters
      including erythrocyte sedimentation rate (ESR), C-reactive protein (CRP),
      albumin, and complete blood count (CBC) were recorded within 24 h on admission
      and transfered from the ICU or died. White blood cell (WBC) count, hemoglobin
      (Hb), red cell distribution width, MPV, platelet distribution width (PDW), and
      platelet count (PC) were obtained from the CBC. RESULTS: Admission PC and MPV
      levels were not different in the survived and dead groups. But in the survived
      group, admission WBC, MPV and PDW levels decreased, while PC increased when
      compared with admission levels. In the dead group, admission MPV and PDW levels
      increased, while PC decreased with respect to admission levels. The admission
      mean PC of the dead group was 182 103, which was above the thrombocytopenia
      limit. The ratio of admission thrombocytopenia was 45.3% in the dead group, which
      was significantly higher than that of the survived group (13.8%) (P < 0.001)
      CONCLUSIONS: Increasing MPV and decreasing platelet count may alert intensivists
      to the worse course of disease in patients who had normal platelet counts at ICU
      admission. The development of thrombocytopenia may also be essential to assessing
      the outcome of ICU patients.

PMID- 24725779
TI  - Muscle pain and use of statin drugs.

PMID- 24725780
TI  - Selected personal highlights of the 8th Interdisciplinary World Congress on Low
      Back and Pelvic Pain, Dubai, October 2013.

PMID- 24725781
TI  - Static and dynamic body balance following provocation of the visual and
      vestibular systems in females with and without joint hypermobility syndrome.
AB  - OBJECTIVES: Joint hypermobility syndrome (JHS) is a heritable disorder of the
      connective tissue characterized by excessive joint movement, musculoskeletal pain
      and neurophysiological deficits (i.e. decreased proprioceptive acuity, altered
      neuromuscular reflexes). Such deficits may affect body balance thus increasing
      the risk of injury. The present study aimed at examining static and dynamic body
      balance following challenge of the visual and vestibular systems in individuals
      with JHS. METHODS: The sample consisted of 21 females with JHS and 20 controls
      without signs of JHS. Static body balance was assessed by the degree of
      anteroposterior and mediolateral deviation of the center of pressure, during 20
      sec single-leg stances with eyes opened (EO), eyes closed (EC) and eyes opened
      with head extension (EO-HE) using a foot pressure platform. Dynamic body balance
      was assessed by the number of landing and balance errors committed during a
      multiple single-leg-hop-stabilization test. RESULTS: Nonparametric analysis
      showed that the JHS-group demonstrated significantly greater (a) mediolateral
      deviation during single-leg-stance with EO (p < 0.01), (b) mediolateral and
      anteroposterior deviation during single-leg-stance with EO-HE (p < 0.05), and (c)
      number of landing errors (p < 0.05) compared to the control group. CONCLUSIONS:
      Poor static balance following challenge of the vestibular system may be justified
      by vestibular deficiency and/or insufficient proprioceptive capabilities of the
      neck. Impairments of dynamic balance in individuals with JHS may be attributed to
      proprioceptive deficits, which can alter feedforward and feedback mechanisms.

PMID- 24725782
TI  - Strain counterstrain technique to decrease tender point palpation pain compared
      to control conditions: a systematic review with meta-analysis.
AB  - BACKGROUND: Strain counterstrain (SCS) is an indirect osteopathic manipulative
      technique that uses passive positioning to relieve tender point (TP) palpation
      pain and associated dysfunction. OBJECTIVE: The purposes of this systematic
      review with meta-analysis were to 1) determine the pooled effect of SCS on TP
      palpation pain compared to a control condition and 2) assess the quality of the
      overall evidence. DATA SOURCE: A search conducted using the MEDLINE with AMED,
      PUBMED, CINAHL, and SCOPUS databases for publications from January 2002 and April
      2012 yielded 29 articles for eligibility screening. STUDY SELECTION: Included
      studies were limited to randomized control trials comparing TP palpation pain
      after isolated SCS treatment compared to control conditions assessed with a
      visual analog scale. Other study designs or manipulative treatments were
      excluded. DATA EXTRACTION: Two reviewers adhered to a predetermined study
      protocol following current Cochrane Collaboration recommendations to
      independently extract the data with standardized extraction forms and assess
      studies for methodological quality and determine risks of bias. RESULTS: Five
      randomized control trials were included for qualitative and quantitative
      analysis. The pooled effect of SCS was a reduction of TP palpation pain (p <
      0.001, 95% CI -0.291 to -0.825). The overall evidence quality was low: while all
      studies met at least 8 of 12 methodological quality criteria, most were low
      quality. CONCLUSIONS: This systematic review and meta-analysis found low quality
      evidence suggesting that SCS may reduce TP palpation pain. Future studies with
      larger samples of better quality studies with patient populations that assess
      long-term pain, impairment, and dysfunction outcomes could enrich the literature.

PMID- 24725783
TI  - Health psychology as a context for massage therapy: a conceptual model with CAM
      as mediator.
AB  - Health psychology represents a context within which massage therapy research,
      education, and practice can be positioned for the mutual benefit of both.
      Furthermore, complementary and alternative medicine (CAM) more often than not
      plays a mediating role in relating massage therapy to health psychology. On
      occasion, though, the linkage between health psychology and massage therapy can
      be quite direct without the mediating influence of CAM. This paper, accordingly,
      advances a conceptual model via both flowchart and Venn diagram displays for
      viewing the health psychology context for massage therapy with the possibility of
      CAM as a mediating factor. Attention is also given to the broad range of issues
      constituting contemporary health psychology as well as its correspondence to an
      equally diverse array of client populations and health conditions addressed in
      massage therapy research. Future directions in the areas of health psychology,
      CAM, and massage therapy are proposed with a view toward a mutual and reciprocal
      benefit accruing to these behavioral and health science arenas. 

PMID- 24725784
TI  - Yoga meets positive psychology: examining the integration of hedonic (gratitude)
      and eudaimonic (meaning) wellbeing in relation to the extent of yoga practice.
AB  - The present study aims to explore the existence of a relationship between the
      extent of yoga practice and two dimensions of psychological wellbeing: meaning in
      life and gratitude. Both of the variables are positive psychology constructs;
      there is theoretical affinity and empirical evidence that they are related to
      overall psychological wellbeing. One hundred and twenty four participants aged 18
      years and above, with yoga experience ranging from none to over six years,
      responded to a number of scales. The extent of yoga practice was measured by the
      number of years during which individuals practiced yoga at least two times a
      week. Participants responded to the following scales: MLQ (Meaning in Life
      Questionnaire) and GQ-6 (Gratitude Questionnaire). This study hypothesised that
      the number of years practicing yoga would be positively correlated to the score
      obtained on the aforementioned scales. Positive correlations were identified
      between the extent of yoga practice and meaning in life and gratitude. Important
      implications regarding the contribution of yoga to both hedonic and Eudaimonic
      happiness are discussed. 

PMID- 24725786
TI  - Chiropractic care for foot drop due to peroneal nerve neuropathy.
AB  - Peroneal nerve palsy is the most common entrapment neuropathy in the lower
      extremity, and the presentation of foot drop is a frequent initial manifestation
      of this disorder. This condition can have a marked influence on the patient's
      activities of daily living, and is classified as 'Impairment of Body Structure.'
      Current literature provides little direction to its evaluation and management,
      and the importance to differentially diagnose the causes of foot drop. Therefore,
      the purpose of this case report is to describe the application of chiropractic
      manipulative therapy, for a 14-year-old female with an insidious onset of foot
      drop. 

PMID- 24725785
TI  - The effects of Pilates exercise on sleep quality in postpartum women.
AB  - Prolonged poor sleeping quality can decrease women's ability to perform their
      maternal and family duties after delivery. The aim of this study was to
      investigate the effects of a Pilates training program on sleep quality in
      primigravida postpartum women in a randomized clinical trial. Eighty postpartum
      women were randomly divided into intervention and control groups (n = 40). Home
      based 30-min Pilates exercises were started 72 h after the delivery and performed
      five times per week for consecutive 8 weeks. Sleep quality was assessed by the
      Pittsburgh Sleep Quality Index (PSQI) prior to the intervention and 4th and 8th
      weeks afterwards. The intervention group showed a significant improvement in
      subjective sleep quality, sleep latency, daytime dysfunction and global PSQI
      score (P < 0.001); however, there was no difference in sleep duration, habitual
      sleep efficiency and sleep disturbance between the groups. In conclusion, Pilates
      exercises appeared to improve sleep quality in primigravida postpartum women.

PMID- 24725787
TI  - The sitting active and prone passive lag test: an inter-rater reliability study.
AB  - BACKGROUND & PURPOSE: To determine inter-rater reliability in identifying a knee
      extension lag using the sitting active and prone passive lag test (SAPLT).
      METHODS: 56 patients with a diagnosis of knee pain were randomly assigned and
      independently examined by two physical therapists at a time, to determine the
      presence of an active or a passive extension lag at the knee. An active lag was
      determined by the inability of the erectly seated subject to actively extend the
      involved knee in maximal dorsiflexion of the ankle to the same level as the
      normal knee held in maximal extension and ankle in maximal dorsiflexion, as seen
      by the levels of the toes. A passive lag was determined by placing the subject
      prone with the knees just past the edge of the table and determining the high
      position of the heel in a fully resting extension position compared to the heel
      on the normal side. RESULTS: For the sitting active lag test, the inter-rater
      reliability was 'good' (Kappa 0.792, SE of kappa 0.115, 95% confidence interval).
      For the prone passive lag test, the inter-rater reliability was 'good' (Kappa
      0.636, SE of kappa 0.136, 95% confidence interval). CONCLUSION: The SAPLT may be
      incorporated as a simple yet effective test to determine the presence of a knee
      extension lag. It identifies the type of restraint, active, passive or both, and
      is suggestive of the most appropriate management.

PMID- 24725789
TI  - A review of the utilization of baropodometry in postural assessment.
AB  - Postural deviations have been linked to a series of different kinds of pain and
      dysfunction. Since the human foot is the basis of support and propulsion for
      gait, and baropodometric analysis assesses dysfunctions of the feet, it may be
      valuable in terms of postural assessment. Therefore, the aim of this literature
      review was to investigate which studies have used this baropodometric equipment
      and how the equipment was used, as well as to discuss the scientific problems and
      solutions associated with the study and clinical practice of baropodometry.
      Twenty-eight of the 48 articles found in the Pubmed and Lilacs databases were
      used. The baropodometer has the potential to provide excellent research in the
      postural field and related areas. However, baropodometry requires standardization
      and an improved calibration system. Further significant scientific papers, using
      properly calibrated equipment, are important in order to improve the quality of
      the technique and display evidence of its clinical and scientific value. 

PMID- 24725788
TI  - Reliability of sagittal pelvic position assessments in standing, sitting and
      during hip flexion using palpation meter.
AB  - The objective of this study was to investigate reliability of assessing sagittal
      pelvic position using the palpation meter (PALM) in healthy subjects while
      sitting, standing and while in different hip flexion angles in standing. Twenty
      healthy subjects were assessed two times by the same examiner, with a 48-h
      interval between test sessions. Reliability indices of PALM measures (intraclass
      correlation coefficient, ICC), standard error of measurement (SEM) and smallest
      detectable change (SDC) were calculated. ICC values showed excellent intra-rater
      reliability for measurements of sagittal pelvic position in standing and sitting
      position and for both standing hip flexion angles (ICC = .89-.96). SEM values
      ranged from .5 degrees  (hip flexion 90 degrees ) to 1.5 degrees  (sitting
      position). SDC values ranged from 1.5 degrees  (hip flexion 90 degrees ) to 4.0
      degrees  (sitting position). The results of this study showed excellent intra
      rater reliability for assessing sagittal pelvic position in standing, sitting and
      hip flexion in healthy subjects using the PALM. 

PMID- 24725790
TI  - Hybrid markerless tracking of complex articulated motion in golf swings.
AB  - Sports video tracking is a research topic that has attained increasing attention
      due to its high commercial potential. A number of sports, including tennis,
      soccer, gymnastics, running, golf, badminton and cricket have been utilised to
      display the novel ideas in sports motion tracking. The main challenge associated
      with this research concerns the extraction of a highly complex articulated motion
      from a video scene. Our research focuses on the development of a markerless human
      motion tracking system that tracks the major body parts of an athlete straight
      from a sports broadcast video. We proposed a hybrid tracking method, which
      consists of a combination of three algorithms (pyramidal Lucas-Kanade optical
      flow (LK), normalised correlation-based template matching and background
      subtraction), to track the golfer's head, body, hands, shoulders, knees and feet
      during a full swing. We then match, track and map the results onto a 2D
      articulated human stick model to represent the pose of the golfer over time. Our
      work was tested using two video broadcasts of a golfer, and we obtained
      satisfactory results. The current outcomes of this research can play an important
      role in enhancing the performance of a golfer, provide vital information to
      sports medicine practitioners by providing technically sound guidance on
      movements and should assist to diminish the risk of golfing injuries. 

PMID- 24725791
TI  - Anatomical structure and nerve branching pattern of the human infraspinatus
      muscle.
AB  - The function of the infraspinatus muscle, critical to rotator cuff function, is
      dependent upon the muscle's structure and innervation pattern. The morphology of
      the infraspinatus muscle has been inconsistently described in the literature.
      Additionally, the branching pattern of the suprascapular nerve in the
      infraspinous fossa has not been addressed in the literature. The purposes of this
      study were to determine: the arrangement of the infraspinatus muscle bellies; the
      branching patterns of the suprascapular nerve to the infraspinatus muscle; if the
      infraspinatus muscle was composed the neuromuscular compartments. Forty-eight
      infraspinatus muscles from 24 embalmed cadavers were studied using standard
      dissection techniques to determine morphological characteristics and innervation
      patterns. Results demonstrated that the infraspinatus muscles were comprised of
      three separate muscular partitions with each partition residing in a thin fascial
      compartment but all residing deep to the posterior scapular fascia. A first order
      suprascapular nerve branch was present in 91.6% of superior, 100% of middle, and
      70.8% of inferior partitions. A first order nerve was present in all 3 muscular
      compartments of the same infraspinatus muscle in 62.5% of cases. Second order
      nerve branches were present in 8.3% of superior, 0% of middle, and 29.2% of
      inferior partitions. These findings help to determine a more complete and
      accurate understanding of the structure of the infraspinatus muscle. A better
      understanding of its structure could lead to a better understanding of the
      function of the muscle. Such information will enable more effective
      rehabilitation strategies for injuries involving the infraspinatus component of
      the rotator cuff. 

PMID- 24725792
TI  - The effect of base of support stability on shoulder muscle activity during closed
      kinematic chain exercises.
AB  - METHOD: A total of thirty eligible subjects (17 female and 13 male, age = 22.26
      +/- 0.99 years, height = 170.96 +/- 8.42 cm, weight = 61.63 +/- 9.92 kg) were
      tested in six different randomly ordered positions. Surface Electromyography
      (EMG) was recorded from the upper trapezius (UT), lower trapezius (LT), serratus
      anterior (SA), long head of the biceps (LB), teres major (TM) and posterior
      deltoid (PD) muscles in the dominant shoulder in 6 different closed kinetic chain
      (CKC) positions. OBJECTIVE: To investigate changes in muscular activity of the
      shoulder muscles at different base of support stability levels. RESULTS: Muscle
      activity was greater in the most stable position for all muscles except UT (P <
      0.01). CONCLUSION: Shoulder muscle activity did not increase in parallel with a
      reduction in base of support stability in the present study.

PMID- 24725793
TI  - Changes in sitting posture affect shoulder range of motion.
AB  - OBJECTIVE: To assess the effect of slouched sitting on shoulder range of motion
      (ROM). METHOD: 30 asymptomatic males aged between 18 and 35 years with no history
      of shoulder problems within the last 6 months. Shoulder ROMs in flexion and
      abduction as well as external rotation and internal rotation in 90 degrees  of
      shoulder abduction were measured while the subjects sat in 3 different sitting
      postures. RESULTS: There were statistically significant mean differences among
      the 3 sitting postures regarding thoracic kyphosis and shoulder ROMs (p < 0.001).
      Post hoc analyzes demonstrated significant differences in all comparisons (p <
      0.001). CONCLUSION: Changes in sitting posture affect shoulder ROMs in all
      directions tested. Greater changes in shoulder ROMs were associated with greater
      increase in thoracic kyphosis. These findings suggest that even subtle changes in
      thoracic kyphosis need to be considered during shoulder evaluation.

PMID- 24725794
TI  - The effects of a global postural reeducation program on an adolescent handball
      player with isthmic spondylolisthesis.
AB  - This report describes and evaluates a physical therapy intervention in a 15-year
      old male handball player with low grade isthmic spondylolisthesis and associated
      spinopelvic misalignment (shear-stress type). Upon examination, increased lumbar
      lordosis, horizontal sacrum and anterior pelvic tilting were mainly associated
      with altered resting length and extensibility of the iliopsoas, hip adductors and
      erector spinae muscles. The intervention was directed at improving the muscles
      resting length and extensibility balance within a global postural alignment
      perspective (global postural reeducation). After the treatment period, lumbar
      lordosis, sacral slope and anterior pelvic tilting decreased 17.2 degrees , 16.5
      degrees  and 15.1 degrees  respectively. Global postural reeducation was
      effective in changing spinopelvic alignment related to low grade isthmic
      spondylolisthesis. This treatment option should be considered as a potential
      nonsurgical alternative for this condition. 

PMID- 24725795
TI  - Does fascia hold memories?
AB  - The idea that tissues may possess some sort of memory is a controversial topic in
      manual medicine, calling for research and clinical exploration. Many bodyworkers,
      at some point in their practice, have experienced phenomena that may be
      interpreted as representing a release of memory traces when working on
      dysfunctional tissues. This feeling may have been accompanied by some type of
      sensory experience, for the therapist and/or the patient. In some cases, early
      traumatic experiences may be recalled. When this happens, the potency of the
      memory may be erased or eased, along with restoration of tissue function. Hence
      the questions: can memories be held in the fascia? And: are these memories
      accessible during manual fascial work? Modern research has proposed a variety of
      different interpretations as to how memory might be stored in soft tissues,
      possibly involving other forms of information storage not exclusively processed
      neurologically (Box 1). 

PMID- 24725796
TI  - Rehabilitative ultrasound imaging of the supraspinatus muscle: Intra- and
      interrater reliability of thickness and cross-sectional area.
AB  - OBJECTIVE: To examine intra- and interrater reliability of thickness and cross
      sectional area (CSA) measurements of the supraspinatus muscle using
      rehabilitative ultrasound imaging (RUSI). METHODS: Two physical therapists
      acquired b-mode images of the supraspinatus muscles in twenty-five healthy
      subjects. Thickness and CSA were measured. Intra- and interrater reliability were
      examined. RESULTS: Intrarater reliability for thickness was high, (ICC1.1 0.91)
      for rater 1 and (ICC1.1 0.92) for rater 2. Intrarater reliability for CSA was
      also high, (ICC1.1 0.90) for rater 1 and (ICC1.1 0.85) for rater 2. Interrater
      reliability for the thickness was high, (ICC3.1 0.86). For CSA, interrater
      reliability was moderate, (ICC3.1 0.70). CONCLUSION: Supraspinatus muscle
      thickness and CSA can be reliably measured by physical therapists in healthy
      subjects. These findings confirm that RUSI has an interesting potential for
      physiotherapy clinical practice, especially to assess morphometric changes in
      skeletal muscles. Further research is needed in subjects with shoulder disorders.

PMID- 24725797
TI  - Effectiveness of myofascial release in the management of chronic low back pain in
      nursing professionals.
AB  - OBJECTIVE: To investigate whether Myofascial release (MFR) when used as an
      adjunct to specific back exercises (SBE) reduces pain and disability in chronic
      low back pain (CLBP) in comparison with a control group receiving a sham
      Myofascial release (SMFR) and specific back exercises (SBE) among nursing
      professionals. DESIGN: Randomized, controlled, single blinded trial. SETTING:
      Nonprofit research foundation clinic in Kerala, India. PARTICIPANTS: Nursing
      professionals (N = 80) with chronic low back pain (CLBP). INTERVENTIONS: MFR
      group or control group. The techniques were administered by physiotherapists
      certified in MFR and consisted of 24 sessions per client over 8 weeks. MAIN
      OUTCOME MEASURE: The McGill Pain Questionnaire (MPQ) was used to assess
      subjective pain experience and Quebec Back Pain Disability Scale (QBPDS) was used
      to assess the disability associated with CLBP. The primary outcome measure was
      the difference in MPQ and QBPDS scores between week 1 (pretest score), week 8
      (posttest score), and follow-up at week 12 after randomization. RESULTS: The
      simple main effects analysis showed that the MFR group performed better than the
      control group in weeks 8 and 12 (P < 0.005). The patients in the MFR group
      reported a 53.3% reduction in their pain and 29.7% reduction in functional
      disability as shown in the MPQ and QBPDS scores in week 8, whereas patients in
      the control group reported a 26.1% and 9.8% reduction in their MPQ and QBPDS
      scores in week 8, which persisted as a 43.6% reduction of pain and 22.7%
      reduction of functional disability in the follow-up at week 12 in the MFR group
      compared to the baseline. The proportion of responders, defined as participants
      who had at least a 50% reduction in pain between weeks 1 and 8, was 73% in the
      MFR group and 0% in the control group, which was 0% for functional disability in
      the MFR and control group. CONCLUSIONS: This study provides evidence that MFR
      when used as an adjunct to SBE is more effective than a control intervention for
      CLBP in nursing professionals.

PMID- 24725798
TI  - The trapezius--clinical & conditioning controversies.

PMID- 24725799
TI  - Conditioning the upper trapezius.

PMID- 24725800
TI  - The effect of dry needling on pain, pressure pain threshold and disability in
      patients with a myofascial trigger point in the upper trapezius muscle.
AB  - Dry needling (DN) has been used recently by physical therapists as a therapy of
      choice for patients with myofascial trigger points (TrP). The purpose of this
      randomized controlled trial was to investigate the effect of DN in the treatment
      of TrPs in the upper trapezius (UT) muscle. A sample of convenience of 33
      patients with TrP in the UT muscle participated in this study. Patients were
      randomly assigned to a standard (N = 17) or experimental group (N = 16). The
      treatment protocol for the standard group consisted of trigger point compression
      technique (TCT) on MTP, while the patients in the experimental group received DN.
      Pain intensity and pressure pain thresholds were assessed for both groups before
      and after the treatment sessions. In addition, the Disability of Arm, Hand, and
      Shoulder (DASH) was administered. Statistical analysis (paired t-test) revealed a
      significant improvement in pain, PPT and DASH scores after treatment in the
      experimental (DN) and standard (TCT) group compared with before treatment (P <
      0.05). The ANCOVA revealed significant differences between the DN and TCT groups
      on the post-measurement VAS score (P = 0.01). There was, however, no significant
      difference between the two groups on the post-measurement score of the PPT (P =
      0.08) and DASH (P = 0.34). DN produces an improvement in pain intensity, PPT and
      DASH and may be prescribed for subjects with TrP in UT muscles especially when
      pain relief is the goal of the treatment. 

PMID- 24725801
TI  - Correlation between severity of temporomandibular disorder and mandibular range
      of motion.
AB  - The aim of the present study was to determine the association between the
      severity of temporomandibular disorder (TMD) and mandibular range of motion
      (ROM). For such, a cross-sectional study was carried out with a sample of 92
      women from the university community. The Fonseca's anamnestic index (FAI) was
      used to determine the severity of TMD, as follows: without TMD (n = 23), mild TMD
      (n = 23), moderate TMD (n = 23), and severe TMD (n = 23). Mouth opening, lateral
      excursion and protrusion of the mandible were measured. Spearman's correlation
      coefficients were calculated to determine the association between the FAI and
      mandibular ROM. Comparisons among groups were performed using the Kruskal-Wallis
      test with Dunn's post hoc test. No significant associations were found between
      TMD severity based on the classification of the FAI and ROM of functional mouth
      opening (rs = -0.001, p = 0.987), maximum active mouth opening (rs = -0.023, p =
      0.822), passive mouth opening (rs = -0.026, p = 0.803), left lateral excursion
      (rs = 0.125, p = 0.231), right lateral excursion (rs = 0.087, p = 0.406) or
      protrusion (rs = -0.148, p = 0.157). Moreover, no statistically significant
      differences among severity groups were found (p > 0.05). Based on the findings of
      the present study, the severity of signs and symptoms of TMD was not associated
      with mandibular range of motion.

PMID- 24725802
TI  - The Modified Bear exercise.

PMID- 24725803
TI  - Effects of human insulin and insulin aspart preparations on levels of IGF-I,
      IGFBPs and IGF bioactivity in patients with type 1 diabetes.
AB  - BACKGROUND: Insulin aspart (IAsp) and its biphasic preparations BIAsp50 and
      BIAsp70 (containing 50% and 70% IAsp, respectively) have distinct glucose
      lowering properties as compared to human insulin (HI). We investigated whether
      this affected the circulating IGF-system which depends on the hepatic insulin
      exposure. METHODS: In a randomized, four-period crossover study, 19 patients with
      type 1 diabetes received identical doses (0.2 U/kg sc) of IAsp, BIAsp70, BIAsp50
      and HI together with a standardized meal. Serum total IGF-I and IGFBP-1 to -3
      were measured by immunoassays for nine hours post-prandially. Bioactive IGF was
      determined by an in-house, cell-based IGF-I receptor kinase activation (KIRA)
      assay. RESULTS: Despite marked differences in peripheral insulin concentrations
      and plasma glucose, the four insulin preparations resulted in parallel decreases
      in IGFBP-1 levels during the first 3 hours, and parallel increases during the
      last part of the study (3-9 hours). Thus, only minor significances were seen.
      Insulin aspart and human insulin resulted in a lower area under the curve (AUC)
      during the first 3 hours as compared to BIAsp70 (p = 0.009), and overall, human
      insulin resulted in a lower IGFBP-1 AUC than BIAsp70 (p = 0.025). Nevertheless,
      responses and AUCs of bioactive IGF were similar for all four insulin
      preparations. Changes in levels of bioactive IGF were inversely correlated to
      those of IGFBP-1, increasing during the first 3 hours, whereafter levels declined
      (-0.83 <= r <= -0.30; all p-values <0.05).Total IGF-I and IGFBP-3 remained stable
      during the 9 hours, whereas IGFBP-2 changed opposite of IGFBP-1, increasing after
      3-4 hours whereafter levels gradually declined. The four insulin preparations
      resulted in similar profiles and AUCs of total IGF-I, IGFBP-2 and IGFBP-3.
      CONCLUSIONS: Despite distinct glucose-lowering properties, the tested insulin
      preparations had similar effects on IGF-I concentration and IGF bioactivity,
      IGFBP-2 and IGFBP-3 as compared to HI; only small differences in IGFBP-1 were
      seen and they did not affect bioactive IGF. Thus, insulin aspart containing
      preparation behaves as HI in regards to the circulating IGF-system. However,
      bioactive IGF appeared to be more sensitive to insulin exposure than total IGF-I.
      The physiological significance of this finding remains to be determined. TRIAL
      REGISTRATION: NCT00888732.

PMID- 24725805
TI  - The effects of catecholamine depletion on the neural response to fearful faces in
      remitted depression.
AB  - Recent evidence suggests that increased psychophysiological response to
      negatively valenced emotional stimuli found in major depressive disorder (MDD)
      may be associated with reduced catecholaminergic neurotransmission. Fourteen
      unmedicated, remitted subjects with MDD (RMDD) and 13 healthy control subjects
      underwent catecholamine depletion with oral alpha-methyl-para-tyrosine (AMPT) in
      a randomized, placebo-controlled, double-blind crossover trial. Subjects were
      exposed to fearful (FF) and neutral faces (NF) during a scan with [15O]H2O
      positron emission tomography to assess the brain-catecholamine interaction in
      brain regions previously associated with emotional face processing. Treatment
      with AMPT resulted in significantly increased, normalized cerebral blood flow
      (CBF) in the left inferior temporal gyrus (ITG) and significantly decreased CBF
      in the right cerebellum across conditions and groups. In RMDD, flow in the left
      posterior cingulate cortex (PCC) increased significantly in the FF compared to
      the NF condition after AMPT, but remained unchanged after placebo, whereas
      healthy controls showed a significant increase under placebo and a significant
      decrease under AMPT in this brain region. In the left dorsolateral prefrontal
      cortex (DLPFC), flow decreased significantly in the FF compared to the NF
      condition under AMPT, and increased significantly under placebo in RMDD, whereas
      healthy controls showed no significant differences. Differences between AMPT and
      placebo of within-session changes in worry-symptoms were positively correlated
      with the corresponding changes in CBF in the right subgenual prefrontal cortex in
      RMDD. In conclusion, this study provided evidence for a catecholamine-related
      modulation of the neural responses to FF expressions in the left PCC and the left
      DLPFC in subjects with RMDD that might constitute a persistent, trait-like
      abnormality in MDD. 

PMID- 24725804
TI  - Addressing population heterogeneity and distribution in epidemics models using a
      cellular automata approach.
AB  - BACKGROUND: The spread of an infectious disease is determined by biological and
      social factors. Models based on cellular automata are adequate to describe such
      natural systems consisting of a massive collection of simple interacting objects.
      They characterize the time evolution of the global system as the emergent
      behaviour resulting from the interaction of the objects, whose behaviour is
      defined through a set of simple rules that encode the individual behaviour and
      the transmission dynamic. METHODS: An epidemic is characterized trough an
      individual-based-model built upon cellular automata. In the proposed model, each
      individual of the population is represented by a cell of the automata. This way
      of modeling an epidemic situation allows to individually define the
      characteristic of each individual, establish different scenarios and implement
      control strategies. RESULTS: A cellular automata model to study the time
      evolution of a heterogeneous populations through the various stages of disease
      was proposed, allowing the inclusion of individual heterogeneity, geographical
      characteristics and social factors that determine the dynamic of the desease.
      Different assumptions made to built the classical model were evaluated, leading
      to following results: i) for low contact rate (like in quarantine process or low
      density population areas) the number of infective individuals is lower than other
      areas where the contact rate is higher, and ii) for different initial spacial
      distributions of infected individuals different epidemic dynamics are obtained
      due to its influence on the transition rate and the reproductive ratio of
      disease. CONCLUSIONS: The contact rate and spatial distributions have a central
      role in the spread of a disease. For low density populations the spread is very
      low and the number of infected individuals is lower than in highly populated
      areas. The spacial distribution of the population and the disease focus as well
      as the geographical characteristic of the area play a central role in the
      dynamics of the desease.

PMID- 24725807
TI  - Pharmacokinetics of topiramate in patients with renal impairment, end-stage renal
      disease undergoing hemodialysis, or hepatic impairment.
AB  - PURPOSE: Topiramate is primarily renally excreted. Chronic renal and hepatic
      impairment can affect the clearance of topiramate. Therefore, the objective was
      to establish dosage guidelines for topiramate in chronic renal impairment, end
      stage renal disease (ESRD) undergoing hemodialysis, or chronic hepatic impairment
      patients. METHODS: In 3 separate open-label, parallel group studies (n=5
      7/group), in patients with mild-moderate and severe renal impairment (based on
      creatinine clearance), ESRD requiring hemodialysis, or moderate-severe hepatic
      impairment (based on Child-Pugh classification) and matching healthy
      participants, pharmacokinetics of a single oral 100mg topiramate was determined.
      RESULTS: Compared with healthy controls, overall exposure (AUC0-infinity) for
      topiramate was higher in mild-moderate (85%) and severe renal impairment (117%),
      consistent with significantly (p<0.05) lower apparent total body clearance (CL/F)
      and renal clearance (CLR), leading to longer elimination half-life. Both CLR and
      CL/F of topiramate correlated well with renal function. CL/F was comparable in
      ESRD and severe renal impairment. Half of usual starting and maintenance dose is
      recommended in moderate-severe renal impairment patients, and those with ESRD.
      Hemodialysis effectively removed plasma topiramate with mean dialysis clearance
      approximately 12-fold greater than CL/F (123.5 mL/min versus 10.8 mL/min).
      Compared with healthy matched, patients with moderate-severe hepatic impairment
      exhibited small increase (29%) in topiramate peak plasma concentrations and AUC0
      infinity values, consistent with lower CL/F (26%). Topiramate was generally well
      tolerated. CONCLUSION: Half of usual dose is recommended for moderate-severe
      renal impairment and ESRD. Supplemental dose may be required during hemodialysis.
      Dose adjustments might not be required in moderate-severe hepatic impairments;
      however, the small sample size limits generalization.

PMID- 24725808
TI  - Reassessment of stiripentol pharmacokinetics in healthy adult volunteers.
AB  - Because children who have been receiving stiripentol for the treatment of Dravet
      syndrome for more than 10 years are now becoming young adults, it is important to
      accurately characterize stiripentol pharmacokinetics in this age range. A double
      blind placebo-controlled dose ranging study was therefore conducted to
      investigate the pharmacokinetics and tolerability of stiripentol in 12 healthy
      volunteers. Each subject received 3 single doses of stiripentol (500, 1000, and
      2000 mg) separated by a wash-out period of 1 week. Pharmacokinetics of
      stiripentol was analyzed for each dose by non-compartmental analysis. Median area
      under the curve (AUC), terminal elimination half-life (t1/2,z) and maximal
      concentration (Cmax) were calculated for between-dose comparison. Safety was
      evaluated based on both clinical and biological criteria. Oppositely to previous
      results, there was no concentration rebounds in the elimination phase, which
      could be the consequence of the food intake. A more than proportional increase in
      the AUC was observed, associated with a significant increase in the t1/2,z, for
      increasing doses (median AUC of 8.3, 31 and 88 mgh/L, and median t1/2,z of 2, 7.7
      and 10h for the 500, 1000, and 2000 mg doses respectively), which confirmed the
      Michaelis-Menten pharmacokinetics of Stiripentol. However, dose-normalized Cmax
      did not significantly vary between doses. Median Michaelis-Menten parameters were
      117 mg/h for Vmax and 1.9 mg/L for Km. No safety concern was observed during the
      study. The present study allowed a better characterization of the disposition
      phase of stiripentol and confirmed its non-linear pharmacokinetic behaviour.
      Further pharmacokinetic/pharmacodynamic studies would be useful to determine the
      optimal dose of stiripentol for the treatment of Dravet patients in adulthood.

PMID- 24725806
TI  - Lifetimes of (214)Po and (212)Po measured with Counting Test Facility at Gran
      Sasso National Laboratory.
AB  - The decays of (214)Po into (210)Pb and of (212)Po into (208)Pb tagged by the
      previous decays from (214)Bi and (212)Bi have been studied inserting quartz vials
      inside the Counting Test Facility (CTF) at the underground laboratory in Gran
      Sasso (LNGS). We find that the mean lifetime of (214)Po is (236.00 +/- 0.42(stat)
      +/- 0.15(syst)) MUs and that of (212)Po is (425.1 +/- 0.9(stat) +/- 1.2(syst))
      ns. Our results are compatible with previous measurements, have a much better
      signal to background ratio, and reduce the overall uncertainties. 

PMID- 24725809
TI  - Tractography of Meyer's Loop asymmetries.
AB  - PURPOSE: The purpose of the current study was to use diffusion tensor imaging
      (DTI) to conduct tractography of the optic radiations (OR) and its component
      bundles and to assess both the degree of hemispheric asymmetry and the inter
      subject variability of Meyer's Loop (ML). We hypothesized that there are
      significant left versus right differences in the anterior extent of ML to the
      temporal pole (TP) in healthy subjects. MATERIALS AND METHODS: DTI data were
      acquired on a 3T Siemens MRI system using a single-shot Spin Echo EPI sequence.
      The dorsal, central and ML bundles of the OR were tracked and visualized in forty
      hemispheres of twenty healthy volunteers. The uncinate fasciculus (UF) was also
      tracked in these subjects so that it could be used as a distinct anatomical
      reference. Measurements were derived for the distance between ML-TP, ML and the
      temporal horn (ML-TH) and ML and the uncinate fasciculus (ML-UF). Paired
      difference t-tests were carried out with SPSS 14.0. RESULTS: ML and the UF were
      successfully tracked and visualized in all 20 volunteers. Significant hemispheric
      asymmetries were found for all measurements with left distances shorter than the
      right (P<0.005). In 50% of the subjects the left ML-UF distance was <=1.9 mm.
      CONCLUSION: The results support our hypothesis and demonstrate that left ML-TP
      distances are significantly shorter than right ML-TP distances. These asymmetries
      are also reflected in shorter left distances between ML-TH and ML-UF. Moreover,
      these results are of interest to left-sided temporal lobe epilepsy surgery
      because it is not only more likely to disturb the anterior extent of ML but also
      renders the often closely located posterior aspect of the left UF more vulnerable
      to potential surgical impact.

PMID- 24725811
TI  - Rapid changes in arousal states of healthy volunteers during robot-assisted gait
      training: a quantitative time-series electroencephalography study.
AB  - BACKGROUND: Robot-assisted gait training (RAGT) is expected to be an effective
      rehabilitative intervention for patients with gait disturbances. However, the
      monotonous gait pattern provided by robotic guidance tends to induce sleepiness,
      and the resultant decreased arousal during RAGT may negatively affect gait
      training progress. This study assessed electroencephalography (EEG)-based,
      objective sleepiness during RAGT and examined whether verbal or nonverbal warning
      sounds are effective stimuli for counteracting such sleepiness. METHODS: Twelve
      healthy men walked on a treadmill for 6 min, while being guided by a Gait
      Assistance Robot, under 3 experimental conditions: with sine-wave sound
      stimulation (SS), verbal sound stimulation (VS), and no sound stimulation (NS).
      The volunteers were provided with warning sound stimulation at 4 min (ST1), 4 min
      20 s (ST2), 4 min 40 s (ST3), and 5 min (ST4) after the start of RAGT. EEGs were
      recorded at the central (Cz) and occipital (O1 and O2) regions (International 10
      20 system) before and during RAGT, and 4-s segments of EEG data were extracted
      from the filtered data during the 8 experimental periods: middle of the eyes
      closed condition; middle of the eyes-open condition; beginning of RAGT;
      immediately before ST1; immediately after ST1, ST2, ST3, and ST4. According to
      the method used in the Karolinska drowsiness test, the power densities of the
      theta, alpha 1, and alpha 2 bands were calculated as indices of objective
      sleepiness. RESULTS: Comparisons of the findings between baseline and before ST
      showed that the power densities of the alpha 1 and 2 bands tended to increase,
      whereas the theta power density increased significantly (P < .05). During NS, the
      power densities remained at a constant high level until after ST4. During SS and
      VS, the power densities were attenuated immediately to the same degree and
      maintained at a constant low level until after ST4. CONCLUSIONS: This study is
      the first to demonstrate that EEG-measured arousal levels decrease within a short
      time during RAGT, but are restored and maintained by intermittent warning sound
      stimulation.

PMID- 24725812
TI  - Predictors of noticing stroke educational campaign.
AB  - BACKGROUND: Long-term campaigns to improve stroke awareness, such as the campaign
      conducted in the Czech Republic since 2006, have not been effective. However, the
      small subpopulation that noticed the campaign had better stroke awareness than
      the population that did not. To better understand this awareness campaign
      responsiveness and to design more successful future campaigns, predictors of
      noticing campaigns were identified. MATERIALS AND METHODS: This study is a
      secondary analysis of cross-sectional nationwide survey data of the Czech
      population older than 40 years, collected in 2009. The survey used a 3-stage
      random sampling method (area, household, and household member) and personal
      semistructured interview questionnaires concerning participants' stroke
      knowledge, demographic characteristics, medical history, and stroke information
      sources. To identify the association between these variables and whether the
      campaign was noticed (the primary outcome of the study), multivariate binary
      logistic regression analysis was used. RESULTS: A total of 601 participants were
      surveyed (90% response rate), 19% of them stated that they noticed the stroke
      awareness campaign. Primary independent predictors of campaign efficiency were
      heart disease (odds ratio [OR], 1.8; 95% confidence interval [CI], 1.0-3.2),
      obesity (OR, 2.4; 95% CI, 1.3-4.7), and current smoking (OR, .4; 95% CI, .3-.7).
      CONCLUSIONS: Tobacco smokers in particular should be targeted by stroke awareness
      campaigns, for example, through health warning labels on cigarette packs. People
      with some stroke risk factors, such as heart disease and obesity, are responsive
      to information about stroke. Therefore, educational campaigns should target the
      groups with increased risk of stroke.

PMID- 24725813
TI  - Potential of magnetic resonance-guided focused ultrasound for intracranial
      hemorrhage: an in vivo feasibility study.
AB  - BACKGROUND: Because of the paucity of effective treatments for intracranial
      hemorrhage (ICH), the mortality rate remains at 40%-60%. A novel application of
      magnetic resonance-guided focused ultrasound (MRgFUS) for ICH may offer an
      alternative noninvasive treatment through the precise delivery of FUS under real
      time MR imaging (MRI) guidance. The purpose of the present study was to optimize
      the parameters for rapid, effective, and safe trans-skull large clot liquefaction
      using in vivo porcine and ex vivo human skull models to provide a clinically
      relevant proof of concept. METHODS: The transcranial effectiveness of MRgFUS was
      tested ex vivo by introducing a porcine blood clot into a human skull, without
      introducing tissue plasminogen activator (tPA). We used an experimental human
      head device to deliver pulsed FUS sonications at an acoustic power of 600-900 W
      for 5-10 seconds. A 3-mL clot was also introduced in a porcine brain and
      sonicated in vivo with one 5-second pulse of 700 W through a bone window or with
      3000 W when treated through an ex vivo human skull. Treatment targeting was
      guided by MRI, and the tissue temperature was monitored online. Liquefied volumes
      were measured as hyperintense regions on T2-weighted MR images. RESULTS: In both
      in vivo porcine blood clot through a craniectomy model and the porcine clot in an
      ex vivo human skull model targeted clot liquefaction was achieved, with only
      marginal increase in temperature in the surrounding tissue. CONCLUSIONS: Our
      results demonstrate the feasibility of fast, efficient, and safe thrombolysis in
      an in vivo porcine model of ICH and in 2 ex vivo models using a human skull,
      without introducing tPA. Future studies will further optimize parameters and
      assess the nature of sonication-mediated versus natural clot lysis, the risk of
      rebleeding, the potential effect on the adjacent parenchyma, and the chemical and
      toxicity profiles of resulting lysate particles.

PMID- 24725814
TI  - Occurrence and predictors of persistent impaired glucose tolerance after acute
      ischemic stroke or transient ischemic attack.
AB  - BACKGROUND: Impaired glucose tolerance is often present in patients with a
      transient ischemic attack (TIA) or ischemic stroke and doubles the risk of
      recurrent stroke. This impaired glucose tolerance can be transient, reflecting an
      acute stress response, or persistent, representing undiagnosed impaired glucose
      metabolism possibly requiring treatment. We aimed to assess the occurrence of
      persistent impaired glucose tolerance after a stroke or TIA and to develop a
      prediction model to identify patients at risk of persistent impaired glucose
      tolerance. METHODS: Patients admitted to the stroke unit or TIA clinic of the
      Erasmus Medical Center with ischemic stroke or TIA and impaired glucose tolerance
      (2-hour postload glucose level of 7.8-11.0 mmol/L) were consecutively enrolled
      between July 2009 and June 2012. The oral glucose tolerance test was repeated
      after 3 months and patients were classified as having transient impaired glucose
      tolerance or persistent impaired glucose tolerance. We developed a prediction
      model by means of a multivariable logistic regression model. We calculated the
      area under the receiver operating characteristic curve (AUC) to quantify the
      performance of the model and the internal validity by bootstrapping. RESULTS: Of
      the 101 patients included, 53 (52%) had persistent impaired glucose tolerance or
      progression to diabetes. These patients were older and more often had
      hypertension and used statins. A prediction model including age, current smoking,
      statin use, triglyceride, hypertension, previous ischemic cardiovascular disease,
      body mass index, and fasting plasma glucose accurately predicted persistent
      impaired glucose tolerance (bootstrapped AUC, .777), with statin use,
      triglyceride, and fasting plasma glucose as the most important predictors.
      CONCLUSIONS: Half of the patients with impaired glucose tolerance after a TIA or
      ischemic stroke have persistent impaired glucose tolerance. We provide a
      prediction model to identify patients at risk of persistent impaired glucose
      tolerance, with statin use, triglyceride, and fasting plasma glucose as the most
      important predictors, which after external validation might be used to optimize
      secondary prevention.

PMID- 24725815
TI  - Reduced smoke-like echo and resolved thrombus in the left atrium with rivaroxaban
      therapy in an acute cardioembolic stroke patient.
AB  - We report a case of a nonvalvular atrial fibrillation (NVAF) patient with acute
      cardioembolic stroke in whom rivaroxaban, an oral direct factor Xa inhibitor,
      reduced a smoke-like echo in the left atrium and resolved a thrombus in the left
      atrial appendage. A 71-year-old man was admitted because of the sudden onset of
      right hemiplegia and aphasia and was diagnosed with acute cardioembolic stroke
      associated with NVAF. The patient had not been treated with warfarin before
      admission, and rivaroxaban therapy (15 mg once daily) was initiated.
      Transesophageal echocardiography was performed on day 8 and a mobile thrombus was
      found in the left atrial appendage, accompanied by a remarkable smoke-like echo
      in the left atrium. Notably, the thrombus was resolved and the smoke-like echo
      was reduced on day 40. No recurrent ischemic stroke occurred. We describe
      favorable effects of rivaroxaban on the reduction of a smoke-like echo and on the
      resolution of a thrombus in the left atrium in an NVAF patient with acute
      cardioembolic stroke. 

PMID- 24725816
TI  - Targeting gallbladder cancer: oncolytic virotherapy with myxoma virus is enhanced
      by rapamycin in vitro and further improved by hyaluronan in vivo.
AB  - BACKGROUND: Gallbladder carcinoma (GBC) is highly lethal, and effective treatment
      will require synergistic anti-tumor management. The study is aimed at
      investigating the oncolytic value of myxoma virus (MYXV) infection against GBC
      and optimizing MYXV oncolytic efficiency. METHODS: We examined the permissiveness
      of GBC cell lines to MYXV infection and compared the effects of MYXV on cell
      viability among GBC and control permissive glioma cells in vitro and in vivo
      after MYXV + rapamycin (Rap) treatment, which is known to enhance cell
      permissiveness to MYXV by upregulating p-Akt levels. We also assessed MYXV +
      hyaluronan (HA) therapy efficiency by examinating Akt activation status, MMP-9
      expression, cell viability, and collagen distribution. We further compared
      hydraulic conductivity, tumor area, and survival of tumor-bearing mice between
      the MYXV + Rap and MYXV + HA therapeutic regimens. RESULTS: MYXV + Rap treatment
      could considerably increase the oncolytic ability of MYXV against GBC cell lines
      in vitro but not against GBC xenografts in vivo. We found higher levels of
      collagen IV in GBC tumors than in glioma tumors. Diffusion analysis demonstrated
      that collagen IV could physically hinder MYXV intratumoral distribution. HA-CD44
      interplay was found to activate the Akt signaling pathway, which increases
      oncolytic rates. HA was also found to enhance the MMP-9 secretion, which
      contributes to collagen IV degradation. CONCLUSIONS: Unlike MYXV + Rap, MYXV + HA
      therapy significantly enhanced the anti-tumor effects of MYXV in vivo and
      prolonged survival of GBC tumor-bearing mice. HA may optimize the oncolytic
      effects of MYXV on GBC via the HA-CD44 interaction which can promote viral
      infection and diffusion.

PMID- 24725820
TI  - Hypovitaminosis D presenting as diffuse myalgia in a 22-year-old woman: a case
      report.
AB  - BACKGROUND: Caused predominantly by insufficient conversion of vitamin D
      precursors by sunlight, hypovitaminosis D is an issue of increasing importance
      worldwide. Although it has been associated with a range of diseases,
      musculoskeletal effects dominate the clinical picture and can lead to significant
      physical debility, whether acute or chronic. Although diagnosis of vitamin D
      deficiency typically occurs in the outpatient setting, it is an easily treatable
      condition, and timely intervention can dramatically improve one's quality of
      life. As highlighted by this case report, hypovitaminosis D may be an important
      but underappreciated etiology of undifferentiated myalgia that, when present,
      warrants initiation of vitamin D repletion therapy even from the emergency
      department (ED). CASE REPORT: A 22-year-old African-American female presented to
      our ED with diffuse myalgia for 4 months. She reported significant debility from
      these symptoms with difficulty ambulating and performing activities of daily
      living. There had been no upper respiratory infection symptoms. The patient had
      discussed all of this with her primary care physician who, despite an extensive
      laboratory work-up, had not identified a definitive etiology. WHY SHOULD AN
      EMERGENCY PHYSICIAN BE AWARE OF THIS?: Chronic pain has stricken the ED patient
      population across the board. Studies demonstrate that the myalgia caused by
      hypovitaminosis D can have a profound and negative impact on an individual's
      lifestyle. Our patient was found to have hypovitaminosis D and had substantial
      improvement with her myalgia and quality of life after treatment. The purpose of
      this report is to help the emergency physician appreciate this disease and
      consider it when clinically appropriate.

PMID- 24725810
TI  - Perioperative outcomes of 6042 nephrectomies in 2012: surgeon-reported results in
      the UK from the British Association of Urological Surgeons (BAUS) nephrectomy
      database.
AB  - OBJECTIVE: To present the perioperative outcomes from the British Association of
      Urological Surgeons (BAUS) nephrectomy dataset for 2012, the first year of public
      reporting of individual surgeon outcomes in the UK. PATIENTS AND METHODS: All
      nephrectomies performed in the year 2012 and recorded in the database were
      analysed. These were divided into simple nephrectomy (SN), partial nephrectomy
      (PN), radical nephrectomy (RN), and nephroureterectomy (NU). The estimated
      capture rate for nephrectomy was 80%. The outcomes measured were 30-day mortality
      (30-DM), Clavien-Dindo complications grade >=III, blood transfusion, conversion
      to open, and length of stay. RESULTS: The overall 30-DM was 0.55% (SN 0.53%; PN
      0.10%; RN 0.52%; NU 1.27%). Clavien-Dindo complications grade >=III were recorded
      in 3.9% of nephrectomies (SN 4.3%; PN 5.4%; RN 3.1%; NU 4.5%). Blood transfusion
      was required during surgical admission for 8.4% of nephrectomies (SN 5.2%; PN
      3.4%; RN 11.1%; NU 8.3%). Conversion to open was carried out in 5.5% of minimally
      invasive nephrectomies (SN 6.1%; PN 4.0%; RN 5.5%; NU 5.6%). Open nephrectomy
      patients remained in hospital for a median of 6 days (SN 7; PN 5; RN 7; NU 8
      days), which was higher than the median 4-day stay (SN 3; PN 4; RN 4; NU 5 days)
      for minimally invasive surgery. CONCLUSIONS: Nephrectomy in 2012 was a safe
      procedure with morbidity and mortality rates comparable with or less than
      published series. The collection of surgeon-specific data should be iterative
      with further refinement of data categories, support for the collection process
      and independent validation of results.

PMID- 24725821
TI  - Ultrasound investigation of leg position to enhance femoral vein exposure for
      cannulation.
AB  - BACKGROUND: Femoral venous access is an essential part of patient care in the
      emergency department (ED). However, current medical literature and texts have not
      dealt with it much using actual patient anatomy. OBJECTIVES: This study aimed to
      show that manipulation of the lower extremities may alter the anatomy to a more
      favorable position for cannulation. METHODS: Ultrasound examination was conducted
      on a prospective sample of ED patients to evaluate anatomical variance of the
      femoral artery and vein overlap as well as the change in femoral vein diameter
      with leg position. Bilateral measurements of the diameter of the vein were taken
      at three different leg positions (straight, abduction, and abduction with
      external rotation). RESULTS: This study enrolled a total of 132 ED patients. Of
      these, 122 (92%) patients showed some degree of overlap on the right and 126
      (95%) patients showed some degree of overlap on the left. There was a
      statistically significant decrease in the percentage of overlap when moving the
      leg from a straightened position to an abducted position, and an additional
      decrease when moving the leg into an abducted and externally rotated position.
      There was also a statistically significant increase in the size of the femoral
      vein with each of these positions. CONCLUSIONS: Up to 95% of people have some
      degree of overlap of the femoral vein by the femoral artery. By positioning the
      leg in an abducted and externally rotated position, the amount of overlap is
      reduced and the diameter of the vein is increased, maximizing the percentage of
      the vein available for cannulation.

PMID- 24725822
TI  - Risk factors for serious underlying pathology in adult emergency department
      nontraumatic low back pain patients.
AB  - BACKGROUND: Nontraumatic low back pain (LBP) is a common emergency department
      (ED) complaint and can be caused by serious pathologies that require immediate
      intervention or that lead to death. OBJECTIVE: The primary goal of this study is
      to identify risk factors associated with serious pathology in adult nontraumatic
      ED LBP patients. METHODS: We conducted a health records review and included
      patients aged >= 16 years with nontraumatic LBP presenting to an academic ED from
      November 2009 to January 2010. We excluded those with previously confirmed
      nephrolithiasis and typical renal colic presentation. We collected 56 predictor
      variables and outcomes within 30 days. Outcomes were determined by tracking
      computerized patient records and performance of univariate analysis and recursive
      partitioning. RESULTS: There were 329 patients included, with a mean age of 49.3
      years; 50.8% were women. A total of 22 (6.7%) patients suffered outcomes,
      including one death, five compression fractures, four malignancies, four disc
      prolapses requiring surgery, two retroperitoneal bleeds, two osteomyelitis, and
      one each of epidural abscess, cauda equina, and leaking abdominal aortic aneurysm
      graft. Risk factors identified for outcomes were: anticoagulant use (odds ratio
      [OR] 15.6; 95% confidence interval [CI] 4.2-58.5), decreased sensation on
      physical examination (OR 6.9; CI 2.2-21.2), pain that is worse at night (OR 4.3;
      CI 0.9-20.1), and pain that persists despite appropriate treatment (OR 2.2; CI
      0.8-5.6). These four predictors identified serious pathology with 91% sensitivity
      (95% CI 70-98%) and 55% specificity (95% CI 54-56%). CONCLUSION: We successfully
      identified risk factors associated with serious pathology among ED LBP patients.
      Future prospective studies are required to derive a robust clinical decision
      rule.

PMID- 24725823
TI  - Point-of-care ultrasound in diagnosing pyomyositis: a report of three cases.
AB  - BACKGROUND: Pyomyositis is a bacterial infection of skeletal muscle that often
      results in deep intramuscular abscesses. The absence of external dermatologic
      manifestations in the early stages of pyomyositis makes this a challenging
      diagnosis. In addition, physical examination findings can be difficult to
      distinguish from more common processes, such as soft-tissue cellulitis.
      Clinicians can fail to diagnose this serious disease in a timely manner,
      resulting in delayed treatment and potential clinical deterioration from sepsis.
      Although advanced imaging modalities, such as computed tomography (CT) and
      magnetic resonance imaging (MRI) provide excellent detail, ultrasound (US) can
      also be used to detect this disease. US can be performed expeditiously at the
      bedside and is less expensive than CT or MRI. It allows the clinician to examine
      the deeper tissue planes of muscle, in which purulent fluid collections will
      develop as pyomyositis advances. CASE REPORT: Three patients presenting with leg
      pain were evaluated with point-of-care (POC) US and diagnosed with pyomyositis.
      The early diagnosis of this condition prompted rapid treatment with
      administration of appropriate antibiotics and involvement of orthopedic surgery.
      Aspiration of fluid allowed for detailed fluid analysis and bacterial cultures.
      Additional diagnostic imaging was performed, confirming the initial US diagnosis.
      WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: POC US can be helpful in
      identifying and further delineating intramuscular abscesses and can subsequently
      lead to expedited and appropriate care in patients who present with extremity
      pain, but lack significant dermatologic changes.

PMID- 24725824
TI  - The usefulness of transplantation studies in monitoring of metals in the marine
      environment: South African experience.
AB  - Due to their close proximity to the point sources of pollution, estuaries and
      harbours are exposed to metals. Mussels are used worldwide to monitor marine
      pollution due to their ability to take up contaminants and the ease of
      transplantation. Mussels were collected from two reference sites and transplanted
      in Richards Bay Harbour (2006 and 2010) and in three harbours. Transplanted and
      resident mussels were removed after 6 weeks exposure and metal concentrations
      were analysed using ICP-MS techniques. Transplanted mussels had higher metal
      concentrations than the resident mussels. This was attributed to regulation of
      metals by the resident mussels. Metal regulation was greater in mussels that are
      continuously submerged as opposed to those that undergo tidal influences. For
      monitoring it is essential that the reference population for transplantation is
      considered carefully as upwelling events in the pristine reference location
      results in significant increases in metal bioaccumulation.

PMID- 24725825
TI  - Occurrence of Enterococcus species with virulence markers in an urban flow
      influenced tropical recreational beach.
AB  - Median enterococci counts of beach water samples gradually increased at
      statistically significant levels (chi2: 26.53, df: 4; p<0.0001) with increasing
      proximity to river influx. The difference in proportion of antibiotic resistant
      enterococci in beach water and river water samples was statistically significant
      (p<0.05) for the tested antibiotics with river isolates generally presenting
      higher resistance frequencies. Virulence genes cyl, esp, gelE and asa were
      detected at varying frequencies (7.32%, 21.95%, 100% and 63.41% respectively)
      among river isolates. On the other hand, the prevalence of these genes was lower
      (0%, 20%, 67.27% and 41.82% respectively) among beach water isolates. Multi-Locus
      Sequence-Typing analysis of Enterococcus faecalis presented four sequence types
      (ST) one of which shared six out of seven tested loci with ST6, a member of the
      clonal complex of multi-drug resistant strains associated with hospital
      outbreaks.

PMID- 24725826
TI  - PMC, a potent hydrophilic alpha-tocopherol derivative, inhibits NF-kappaB
      activation via PP2A but not IkappaBalpha-dependent signals in vascular smooth
      muscle cells.
AB  - The hydrophilic alpha-tocopherol derivative, 2,2,5,7,8-pentamethyl-6
      hydroxychromane (PMC), is a promising alternative to vitamin E in clinical
      applications. Critical vascular inflammation leads to vascular dysfunction and
      vascular diseases, including atherosclerosis, hypertension and abdominal aortic
      aneurysms. In this study, we investigated the mechanisms of the inhibitory
      effects of PMC in vascular smooth muscle cells (VSMCs) exposed to pro
      inflammatory stimuli, lipopolysaccharide (LPS) combined with interferon (IFN)
      gamma. Treatment of LPS/IFN-gamma-stimulated VSMCs with PMC suppressed the
      expression of inducible nitric oxide synthase (iNOS) and matrix metalloproteinase
      9 in a concentration-dependent manner. A reduction in LPS/IFN-gamma-induced
      nuclear factor (NF)-kappaB activation was also observed in PMC-treated VSMCs. The
      translocation and phosphorylation of p65, protein phosphatase 2A (PP2A)
      inactivation and the formation of reactive oxygen species (ROS) were
      significantly inhibited by PMC in LPS/IFN-gamma-activated VSMCs. However, neither
      IkappaBalpha degradation nor IkappaB kinase (IKK) or ribosomal s6 kinase-1
      phosphorylation was affected by PMC under these conditions. Both treatments with
      okadaic acid, a PP2A-selective inhibitor, and transfection with PP2A siRNA
      markedly reversed the PMC-mediated inhibition of iNOS expression, NF-kappaB
      promoter activity and p65 phosphorylation. Immunoprecipitation analysis of the
      cellular extracts of LPS/IFN-gamma-stimulated VSMCs revealed that p65 colocalizes
      with PP2A. In addition, p65 phosphorylation and PP2A inactivation were induced in
      VSMCs by treatment with H(2)O(2), but neither IkappaBalpha degradation nor IKK
      phosphorylation was observed. These results collectively indicate that the PMC
      mediated inhibition of NF-kappaB activity in LPS/IFN-gamma-stimulated VSMCs
      occurs through the ROS-PP2A-p65 signalling cascade, an IKK-IkappaBalpha
      independent mechanism. Therapeutic interventions using PMC may therefore be
      beneficial for the treatment of vascular inflammatory diseases.

PMID- 24725827
TI  - Differentiation of compressive from glaucomatous optic neuropathy with spectral
      domain optical coherence tomography.
AB  - PURPOSE: To compare optic disc topography in eyes with compressive optic
      neuropathy (CON) and open-angle glaucoma (OAG) using spectral-domain (SD) optical
      coherence tomography (OCT) and Heidelberg retinal tomograph (HRT) (Heidelberg
      Engineering GmbH, Heidelberg, Germany). DESIGN: Cross-sectional, observational
      study. PARTICIPANTS: A total of 200 eyes from 123 patients with CON (69 eyes) or
      OAG (58 eyes) and controls (73 eyes). METHODS: Univariate and multivariate
      analyses of HRT parameters, SD-OCT circumpapillary retinal nerve fiber layer
      (RNFL) thickness, and optic nerve head (ONH) parameters. MAIN OUTCOME MEASURES:
      Circumpapillary RNFL, OCT ONH parameters, and HRT parameters. RESULTS: The
      univariate analysis of OCT parameters demonstrated significant differences
      between the temporal and nasal quadrants; clock hours 3 (55 vs. 73 MUm), 4, 8
      (93.9 vs. 70.7 MUm), 9, and 10; vertical cup-to-disc ratio (C:D) (0.6 vs. 0.8)
      and cup volume (0.2 vs. 0.5) (P<0.001) between patients with CON and OAG,
      respectively. The CON discs were significantly different from normal discs for
      all OCT parameters except cup volume. The CON discs were not significantly
      different from normal discs for HRT parameters, except for mean RNFL thickness
      and cup shape measure. The OAG discs were significantly different from normal
      discs in all HRT and OCT parameters (P<0.001). Multivariate analysis demonstrated
      that the OCT 3 o'clock temporal sector, average C:D ratio, vertical C:D ratio,
      and cup volume measurements were able to differentiate OAG from CON. CONCLUSIONS:
      Compressive optic neuropathy is associated with significantly thinner nasal and
      temporal sectors compared with OAG, whereas OAG results in larger cups and cup
      volume with OCT measurements. The Heidelberg retinal tomograph is not able to
      differentiate CON from normal discs.

PMID- 24725828
TI  - Hemicraniectomy for malignant middle cerebral artery infarction: current status
      and future directions.
AB  - Malignant middle cerebral artery infarction is a life-threatening sub-type of
      ischemic stroke that may only be survived at the expense of permanent disability.
      Decompressive hemicraniectomy is an effective surgical therapy to reduce
      mortality and improve functional outcome without promoting most severe
      disability. Evidence derives from three European randomized controlled trials in
      patients up to 60 years. The recently finished DEcompressive Surgery for the
      Treatment of malignant INfarction of the middle cerebral arterY - II trial gives
      now high-level evidence for the effectiveness of decompressive hemicraniectomy in
      patients older than 60 years. Nevertheless, pressing issues persist that need to
      be answered in future clinical trials, e.g. the acceptable degree of disability
      in survivors of malignant middle cerebral artery infarction, the importance of
      aphasia, and the best timing for decompressive hemicraniectomy. This review
      provides an overview of the current diagnosis and treatment of malignant middle
      cerebral artery infarction with a focus on decompressive hemicraniectomy and
      outlines future perspectives. 

PMID- 24725829
TI  - Exploring stimulant treatment in ADHD: narratives of young adolescents and their
      parents.
AB  - BACKGROUND: Young adolescents' and their parents' experiences with Attention
      Deficit/Hyperactivity Disorder (ADHD) and its treatment were explored to
      investigate beliefs and attitudes regarding use of stimulant medication, and
      their influence on treatment decisions. METHODS: Using in-depth qualitative
      interviews, 12 adolescents with ADHD aged 12 - 15 years, and their parents
      described their experiences of ADHD and its treatment. Twenty four interviews, 12
      with adolescents and 12 with their parents elicited detailed descriptions of
      beliefs about ADHD, attitudes about stimulant use and the circumstances
      surrounding treatment decisions. Verbatim transcripts were iteratively analyzed
      by a team of researchers following an interpretive interactionist framework.
      RESULTS: Young people offered three themes describing ADHD: 1) personality trait,
      2) physical condition or disorder, and 3) minor issue or concern. Regarding
      medication use, youth described 1) benefits, 2) changes in sense of self, 3)
      adverse effects, and 4) desire to discontinue use. Parents' beliefs were more
      homogeneous than youth beliefs, describing ADHD as a disorder requiring
      treatment. Most parents noted benefits from stimulant use. Themes were 1)
      medication as a last resort, 2) allowing the child to reach his or her potential;
      and 3) concerns about adverse and long-term effects. Families described how
      responsibility for treatment decisions is transferred from parent to adolescent
      over time. CONCLUSIONS: Young adolescents can have different beliefs about ADHD
      and attitudes about medication use from their parents. These beliefs and
      attitudes influence treatment adherence. Incorporating input from young
      adolescents when making clinical decisions could potentially improve continuity
      of treatment for youth with ADHD.

PMID- 24725830
TI  - Ascending-to-descending aortic bypass: a simple solution to a complex problem.
AB  - BACKGROUND: Surgical correction of complex aortic coarctation can be associated
      with significant risks. Extraanatomic bypass may represent a safer alternative.
      METHODS: Between January 1985 and December 2012, 80 consecutive patients with
      complex coarctation underwent ascending-to-descending aortic bypass through a
      median sternotomy. Patients were a median age of 42 years (range, 15 to 75
      years), and 51 (64%) were males. Recurrent coarctation was present in 52 patients
      (65%), with 6 (8%) having undergone balloon dilatation. Uncontrolled hypertension
      was present in 63 patients (79%). The most common concomitant pathology was
      aortic valve stenosis in 21 patients (26%), subaortic stenosis in 10 (13%), and
      Shone complex in 4 (5%). RESULTS: There were no early deaths. The most common
      concomitant procedures were aortic valve replacement, coronary artery bypass
      grafting, and resection of subaortic stenosis. The mean aortic cross-clamp and
      cardiopulmonary bypass times were 33 +/- 40 and 106 +/- 54 minutes, respectively.
      Morbidity included atrial fibrillation in 17 patients (21%) and reexploration for
      bleeding in 6 (8%). There was no paraplegia or stroke. Upper extremity blood
      pressure significantly improved (p < 0.001). Mean systolic blood pressure
      decreased from 153 +/- 26 mm Hg preoperatively to 123 +/- 15 mm Hg
      postoperatively. Mean follow-up was 7 +/- 6 years (maximum, 22 years). Late
      deaths occurred in 5 patients (6%) and were not graft-related. Three patients
      (4%) required reoperation for repair of periprosthetic regurgitation in 2 and
      mitral valve replacement in 1. CONCLUSIONS: The ascending-to-descending aortic
      bypass can be performed with low morbidity and mortality. It is an effective
      solution to complex aortic coarctation and represents a safe single-stage
      approach for patients with concomitant cardiac pathology.

PMID- 24725831
TI  - Association between preoperative statin use and acute kidney injury biomarkers in
      cardiac surgical procedures.
AB  - BACKGROUND: Acute kidney injury (AKI) is a serious complication of cardiac
      operations for which there remains no specific therapy. Animal data and several
      observational studies suggest that statins prevent AKI, but the results are not
      conclusive, and many studies are retrospective in nature. METHODS: We conducted a
      multicenter prospective cohort study of 625 adult patients undergoing elective
      cardiac operations. All patients were taking statins and were grouped according
      to whether statins were continued or held in the 24 hours before operation. The
      primary outcome was AKI as defined by a doubling of serum creatinine or dialysis.
      The secondary outcome was the peak level of several kidney injury biomarkers. The
      results were adjusted for demographic and clinical factors. RESULTS: Continuing
      (vs holding) a statin before operation was not associated with a lower risk of
      AKI, as defined by a doubling of serum creatinine or dialysis (adjusted relative
      risk [RR] 1.09; 95% confidence interval [CI] 0.44, 2.70). However, continuing a
      statin was associated with a lower risk of elevation of the following AKI
      biomarkers: urine interleukin-18, urine neutrophil gelatinase-associated
      lipocalin, urine kidney injury molecule-1, and plasma neutrophil gelatinase
      associated lipocalin (adjusted RR 0.34; 95% CI 0.18, 0.62), (adjusted RR 0.41;
      95% CI 0.22, 0.76), (adjusted RR 0.37; 95% CI 0.20, 0.76), (adjusted RR 0.62; 95%
      CI 0.39, 0.98), respectively. CONCLUSIONS: Statins may prevent kidney injury
      after cardiac operations, as evidenced by lower levels of kidney injury
      biomarkers.

PMID- 24725833
TI  - Bioprosthetic valve durability after stentless aortic valve replacement: the
      effect of implantation technique.
AB  - BACKGROUND: The Freestyle stentless bioprosthesis (FSB) (Medtronic Inc,
      Minneapolis, MN) is implanted using 2 techniques-subcoronary or aortic root
      replacement. Our objective was to determine whether the implantation technique
      had an impact on late reoperation for structural valve deterioration (SVD).
      METHODS: Between 1993 and 2013, 531 patients underwent aortic valve replacement
      (AVR) or aortic root reconstruction with an FSB. The implantation technique was
      subcoronary in 430 patients (group S) and root replacement in 101 patients (group
      R). Median follow-up was 10.8 years for group S patients and 10.1 years for group
      R patients. The follow-up was complete in all patients. RESULTS: Mean age was
      68.2 years in group S and 65.2 in group R (p = 0.001). In-hospital mortality was
      3.5% and 5.0% in group S and group R, respectively (p = 0.56). Late reoperation
      was required in 60 (14.5%) hospital survivors in group S and 8 (8.3%) hospital
      survivors in group R. There were 36 reoperations in group S and 3 in group R for
      SVD. Freedom from reoperation for SVD was 94.6% and 76.7% at 10 and 15 years,
      respectively, in group S, and 98.9% and 88.1% at 10 and 15 years, respectively,
      for group R (p = 0.04). The subcoronary technique was an independent risk factor
      for late reoperation for SVD (p = 0.002). Implantation technique was not
      independently associated with in-hospital and long-term mortality. CONCLUSIONS:
      The Freestyle bioprosthesis implanted as a root replacement was associated with
      less reoperation for SVD over the long term compared with the subcoronary
      technique. However, the method of implantation has no influence on early and long
      term survival.

PMID- 24725832
TI  - Serum brain natriuretic peptide and risk of acute kidney injury after cardiac
      operations in children.
AB  - BACKGROUND: Acute kidney injury (AKI) after pediatric cardiac operations is
      associated with poor outcomes and is difficult to predict. We conducted a
      prospective study to evaluate whether preoperative brain natriuretic peptide
      (BNP) levels predict postoperative AKI among children undergoing cardiac
      operations. METHODS: This was a three-center, prospective study (2007-2009) of
      277 children undergoing cardiac operations (n = 121, aged <2 years) with
      available preoperative BNP values. Preoperative BNP was measured and categorized
      into tertiles. The performance of BNP was evaluated alone and in combination with
      clinical factors. AKI was defined as doubling of serum creatinine or need for
      acute dialysis. RESULTS: Postoperative AKI occurred in 165 children (60%), with
      118 cases (43%) being mild and 47 cases (17%) severe. Preoperative BNP was not
      associated with increased risk of mild or severe postoperative AKI and did not
      significantly improve AKI risk prediction when added to clinical models.
      Preoperative BNP was, however, associated with several clinical outcomes,
      including length of stay and mechanical ventilation. The results were similar
      when the analysis was repeated in the subset of children younger than 2 years of
      age or when the association of postoperative BNP and AKI was evaluated.
      CONCLUSIONS: Preoperative BNP levels did not predict postoperative AKI in this
      cohort of children undergoing cardiac operations. Both preoperative and
      postoperative BNP levels are associated with postoperative outcomes. Clinical
      Trial Registration at Clinicaltrials.gov as NCT00774137.

PMID- 24725834
TI  - Stem cells accumulate on a decellularized arterial xenograft in vivo.
AB  - BACKGROUND: Surgical interest in complete arterial revascularization is
      expanding, but some patients lack suitable conduits for this goal. The field of
      stem cell biology is rapidly expanding and, together with the concepts of tissue
      engineering, offers the promise of growing autologous grafts in the laboratory.
      We aim to develop a model using human arteries as vascular grafts in a murine
      model and to assess the cellular accumulation on these grafts. METHODS: Human
      arterial samples were collected and decellularized using an ionic detergent.
      These vessel scaffolds were then used as grafts in an in vivo mouse model, and
      the cellular accumulation on them was examined histologically and by cell culture
      with assessment of their physiologic properties. RESULTS: Left internal mammary
      artery branches were fully decellularized and successfully implanted into a
      murine model. Grafts were repopulated by cells expressing stem cell markers
      cluster of differentiation 34 and stage-specific embryonic antigen, and
      subsequently expressed markers of mature endothelial and smooth muscle cells
      (cluster of differentiation 31, calponin, and myosin heavy chain). The migratory
      capacity of the cultured cells was significantly higher than that of mouse smooth
      muscle cells (p < 0.001). CONCLUSIONS: We describe the successful use of human
      arteries in a murine graft model, allowing the study of repopulation.
      Decellularized grafts are repopulated by cells expressing stem cell markers and
      subsequently express smooth muscle and endothelial cell markers. This model has
      the potential to be used for further development of laboratory-grown vascular
      grafts.

PMID- 24725835
TI  - Failed autograft after the ross procedure in children: management and outcome.
AB  - BACKGROUND: Autograft dilatation (AD) and aortic insufficiency (AI) after the
      Ross procedure are the most common causes of late autograft failure. The purpose
      of this study was to examine the results of valve-sparing root replacement
      (modified David) and composite root replacement. METHODS: We performed a
      retrospective review of all children (n=78) undergoing a Ross procedure at our
      Center from 1993 to 2011. RESULTS: Median follow-up was 10 years (1to 18 years).
      Freedom from autograft reoperation was 94% at 5 years, and 65% at 15 years.
      Freedom from greater than 2+ autograft AI was 93% at 5 years and 76% at 15 years.
      Autograft reoperation was necessary in 22 patients, at a median interval of 8.7
      years after the original procedure. Indications for reoperation were AI with
      autograft dilatation in 15 patients, AI without dilatation in 2 patients, and AD
      without AI in 5 patients. Surgical procedures used at reoperation included valve
      sparing root replacement in 14 patients, root replacement either mechanical or
      biologic valved conduit in 6 patients, and valve replacement in 2 patients. At a
      mean follow-up of 5.8 years after reoperation, 4 patients from the valve-sparing
      group underwent second reoperation (valve replacement). Freedom from second
      autograft reoperation was 71% for patients after a valve sparing procedure and
      100% for patients after an aortic valve or root replacement (Bentall procedure)
      at 5 years. CONCLUSIONS: Autograft valve-sparing root replacement and composite
      aortic root replacement are effective treatments for aortic root dilation and AI
      after the Ross procedure. The potential of late autograft insufficiency after
      valve-sparing root replacement warrants annual follow-up.

PMID- 24725836
TI  - Percutaneous fiducial localization for thoracoscopic wedge resection of small
      pulmonary nodules.
AB  - BACKGROUND: The advent of high-resolution computed tomography scanning and
      increase in use of chest imaging for high-risk patients has led to an increase in
      the identification of small pulmonary nodules. The ability to locate and remove
      these nodules through a thoracoscopic approach is difficult. The purpose of this
      study is to report our experience with fiducial localization and percutaneous
      thoracoscopic wedge resection of small pulmonary nodules. METHODS: This is a
      retrospective analysis of our patients who underwent computed tomography-guided
      fiducial localization of pulmonary nodules. Nodules were identified with
      intraoperative fluoroscopy and removed by thoracoscopic wedge resection. RESULTS:
      Sixty-five nodules were removed in 58 patients. Removal was successful in 98% of
      patients (57 of 58); 79% of the nodules (53 of 65) were cancers; 20% of these
      were primary lung cancers of which 9 were pure ground-glass opacities. Mean size
      of the nodules was 9.9 +/- 4.6 mm (range, 3 to 24 mm). Mean depth from visceral
      pleural surface was 18.7 +/- 12 mm (range, 2 to 35 mm). Mean procedure time was
      58.7 +/- 20.1 minutes (range, 30 to 120), and mean length of stay was 2 days
      (range, 1 to 6). Complications occurred in 3 patients and included fiducial
      embolization, fiducial migration, and parenchymal hematoma. CONCLUSIONS: Fiducial
      localization facilitates identification and removal of small pulmonary nodules
      and alleviates the need for direct nodule palpation. As shown by our series,
      thoracoscopic wedge resection with fiducial localization is an accurate and
      efficient technique. This method provides a standardized means by which to resect
      small and deep pulmonary nodules or ground-glass opacities.

PMID- 24725837
TI  - Twenty-five years' experience with a trap-door thoracotomy modified with
      disconnection of the first rib for tumors invading the anterior superior sulcus.
AB  - BACKGROUND: A procedure of modified trap-door thoracotomy and our 25 years'
      experience in 33 patients with tumors invading the anterior superior sulcus are
      presented. METHODS: The modified portion of the original trap-door thoracotomy is
      the disconnection of the first rib from inside the thorax. Tumors consisted of
      lung cancer in 13 patients, thyroid cancer in 10, thymic tumor in 5, neurogenic
      tumor in 3, germ cell tumor in 1, and metastatic tumor in 1. Of the 33, 16
      patients underwent a combined resection of the invaded organs, which included the
      brachiocephalic and subclavian veins in 4 patients, brachiocephalic vein in 3,
      thoracic wall in 6, trachea in 2, and trachea and brachiocephalic artery in 1.
      Combined resections of the trachea in the total 3 patients were treated with a
      sleeve resection and reconstruction, and those of the brachiocephalic and
      subclavian veins in 2 patients and brachiocephalic artery in 1 were reconstructed
      by a vessel graft. RESULTS: Compared with the original trap-door thoracotomy, the
      additional disconnection of the first rib from inside the thorax provided a more
      adequate opening in the chest wall and more extensive exposure of the entire
      superior sulcus region, which enabled the complete resection of the tumors in all
      patients. A postoperative complication occurred in 1 patient, who had
      chylothorax. CONCLUSIONS: A trap-door thoracotomy modified with a disconnection
      of the first rib enabled a sufficient approach for resection of tumors invading
      the anterior superior sulcus.

PMID- 24725838
TI  - Hybrid approach of percutaneous coronary intervention followed by minimally
      invasive valve operations.
AB  - BACKGROUND: A subset of patients requiring coronary revascularization and valve
      operations may benefit from a hybrid approach of percutaneous coronary
      intervention (PCI) followed by a minimally invasive valve operation, rather than
      the standard combined median sternotomy coronary artery bypass grafting (CABG)
      and a valve operation. This study sought to evaluate the outcomes of this
      approach in a heterogeneous group of patients with concomitant coronary artery
      and valvular disease. METHODS: We retrospectively evaluated 222 consecutive
      patients with coronary artery and valvular heart disease who underwent PCI
      followed by elective minimally invasive valve operations at our institution
      between February 2009 and August 2013. RESULTS: A total of 136 men and 86 women
      were identified. The mean age was 74.6 +/- 8.2 years, with 181 (81.5%) undergoing
      1-vessel, 27 (12.2%) undergoing 2-vessel, and 14 (6.3%) undergoing 3-vessel PCI.
      Within a median of 38 days (interquartile range [IQR] 18-65 days), 182 (82%)
      patients underwent primary and 34 (15.3%) underwent repeated valve operations,
      which consisted of 185 (83.3%) single-valve and 37 (16.7%) double-valve
      procedures. Operative mortality occurred in 8 patients (3.6%). At a mean follow
      up of 16.2 +/- 12 months, 6 patients required PCI, with target-vessel
      revascularization performed in 4 patients (2.1%). Survival at 1 and 4.5 years was
      91.9% and 88.3%, respectively. CONCLUSIONS: In a heterogeneous group of patients,
      a hybrid approach of PCI followed by minimally invasive valve operations in
      patients undergoing primary or repeated valve operations can be performed with
      excellent outcomes.

PMID- 24725839
TI  - Increased exposure improves recruitment: early results of a program designed to
      attract medical students into surgical careers.
AB  - BACKGROUND: In recent years, general surgery and surgical subspecialty residency
      interests have remained somewhat static among medical students, casting some
      doubt on recruitment of the best students. A summer research program was designed
      to introduce interested medical students to surgical careers. METHODS: In 2003,
      the division of cardiac surgery instituted an 8-week structured summer research
      experience for second-year medical students. Three students were competitively
      chosen from a pool of 20 to 30 interested applicants every year. They were taught
      basic operative suturing and knot-tying techniques. Students participated in
      large animal research projects, witnessed clinical operations, and developed
      individual clinical projects with an attending cardiac surgeon. The summer
      experience culminated with oral presentations to the cardiac surgery division,
      with many students producing manuscripts for publication or presentation at
      national meetings. RESULTS: From 2003 to 2012, 30 students participated in the
      program. Of 23 participants who had applied for residency, 12 (52.2%) matched
      into general surgery or a surgical subspecialty, including 3 into plastic
      surgery, 2 into cardiothoracic surgery, 1 into orthopedic surgery, and 1 into
      neurosurgery. These students produced 64 publications and presented at 51
      national and regional meetings. CONCLUSIONS: These results suggest that an 8
      week, structured program introducing students to cardiothoracic surgery can
      successfully attract students into surgical careers. The percentage (52%) of
      these students entering a surgical career compares favorably with national
      residency match results (16%) and graduating Johns Hopkins medical students
      (22%). Increased effort for early exposure to surgery may be a key factor in
      generating and securing surgical interest among medical students.

PMID- 24725840
TI  - Glucagon-like peptide 1-potentiated insulin secretion and proliferation of
      pancreatic beta-cells.
AB  - Glucagon-like peptide-1 (GLP-1) is the primary incretin hormone secreted from the
      intestine upon uptake of food to stimulate insulin secretion from pancreatic beta
      cells. GLP-1 exerts its effects by binding to its G-protein coupled receptors and
      subsequently activating adenylate cyclase, leading to generation of cyclic
      adenosine monophosphate (cAMP). cAMP stimulates insulin secretion via activation
      of its effectors PKA and Epac2 in pancreatic beta-cells. In addition to its
      insulinotropic effects, GLP-1 also preserves pancreatic beta-cell mass by
      stimulating beta-cell proliferation. Unlike the action of sulphonylureas in
      lowering blood glucose levels, action of GLP-1 is affected by and interplays with
      glucose levels. Due to such advantages, GLP-1-based therapeutics have been
      rapidly developed and used clinically for treatment of type 2 diabetes. However,
      molecular mechanisms underlying how GLP-1 potentiates diminished glucose
      stimulated insulin secretion and beta-cell proliferation under diabetic
      conditions are not well understood. Here, we review the actions of GLP-1 in
      regulation of insulin secretion and pancreatic beta-cell proliferation. 

PMID- 24725841
TI  - Taste hyposensitivity in Japanese schoolchildren.
AB  - BACKGROUND: There is some research on taste disorder/hyposensitivity in special
      groups such as the elderly or patients presenting with specific taste problems,
      however few studies have been conducted among young populations. The objectives
      of this study were to estimate the prevalence of taste hyposensitivity and to
      investigate the relationship between taste hyposensitivity and oral health status
      in Japanese schoolchildren. METHODS: Subjects were 237 primary and 112 junior
      high school students in Saitama Prefecture, Japan. In total, 349 (boys: 181,
      girls: 168) students aged 6-15 years participated in the study. Oral examinations
      and whole-mouth taste tests using four tastes (sweet, salt, sour and bitter)
      solutions were conducted on the subjects. A subject who could not recognize the
      taste of the solution was defined as demonstrating hyposensitivity. RESULTS:
      Hyposensitivity was observed in 6.3% of all subjects for sweet-taste, 14.3% for
      salt-taste, 20.9% for sour-taste and 6.0% for bitter-taste. The prevalence of
      sweet, sour and bitter-taste hyposensitivity decreased as the subjects' grade
      advanced. In contrast, the prevalence of salt-taste hyposensitivity increased in
      7th-9th grade subjects. Furthermore, the prevalence of bitter-taste
      hyposensitivity was significantly higher in males than females among 1st-3rd
      graders.Taste hyposensitivity had little association with oral health status,
      such as decayed teeth, filled teeth, dental plaque, gingival status and tongue
      coating. CONCLUSIONS: In this study, taste hyposensitivity was observed in 6.0%
      20.9% of the students. There was little association between taste hyposensitivity
      and oral health status. The current study implies that the factors affecting the
      taste hyposensitivity in children may different from those in the elderly.
      Therefore it is necessary to further investigate the causes of taste
      hyposensitivity among younger generation.

PMID- 24725842
TI  - dRiskKB: a large-scale disease-disease risk relationship knowledge base
      constructed from biomedical text.
AB  - BACKGROUND: Discerning the genetic contributions to complex human diseases is a
      challenging mandate that demands new types of data and calls for new avenues for
      advancing the state-of-the-art in computational approaches to uncovering disease
      etiology. Systems approaches to studying observable phenotypic relationships
      among diseases are emerging as an active area of research for both novel disease
      gene discovery and drug repositioning. Currently, systematic study of disease
      relationships on a phenome-wide scale is limited due to the lack of large-scale
      machine understandable disease phenotype relationship knowledge bases. Our study
      innovates a semi-supervised iterative pattern learning approach that is used to
      build an precise, large-scale disease-disease risk relationship (D1 -> D2)
      knowledge base (dRiskKB) from a vast corpus of free-text published biomedical
      literature. RESULTS: 21,354,075 MEDLINE records comprised the text corpus under
      study. First, we used one typical disease risk-specific syntactic pattern (i.e.
      "D1 due to D2") as a seed to automatically discover other patterns specifying
      similar semantic relationships among diseases. We then extracted D1 -> D2 risk
      pairs from MEDLINE using the learned patterns. We manually evaluated the
      precisions of the learned patterns and extracted pairs. Finally, we analyzed the
      correlations between disease-disease risk pairs and their associated genes and
      drugs. The newly created dRiskKB consists of a total of 34,448 unique D1 -> D2
      pairs, representing the risk-specific semantic relationships among 12,981
      diseases with each disease linked to its associated genes and drugs. The
      identified patterns are highly precise (average precision of 0.99) in specifying
      the risk-specific relationships among diseases. The precisions of extracted pairs
      are 0.919 for those that are exactly matched and 0.988 for those that are
      partially matched. By comparing the iterative pattern approach starting from
      different seeds, we demonstrated that our algorithm is robust in terms of seed
      choice. We show that diseases and their risk diseases as well as diseases with
      similar risk profiles tend to share both genes and drugs. CONCLUSIONS: This
      unique dRiskKB, when combined with existing phenotypic, genetic, and genomic
      datasets, can have profound implications in our deeper understanding of disease
      etiology and in drug repositioning.

PMID- 24725843
TI  - Prevalence of stroke and coexistent conditions: disparities between indigenous
      and nonindigenous Western Australians.
AB  - BACKGROUND: Worldwide, the prevalence of stroke is poorly described in indigenous
      populations, despite high stroke burden. This paper reports the average point
      prevalence of hospitalized stroke and coexistent conditions (2007-2011) in
      indigenous and nonindigenous people in Western Australia, the largest and most
      sparsely populated Australian jurisdiction. METHODS: Using state-wide linked
      hospital and mortality data, indigenous and nonindigenous prevalent stroke cases
      (aged 25-84 years) were identified after reviewing stroke admissions over a fixed
      20-year look-back period. Prevalent cases were those alive at midyear of each
      study year. The 2007-2011 period prevalence was a weighted average of annual
      prevalence. Histories of 11 comorbidities were identified using the 20-year look
      back period. RESULTS: Indigenous cases comprised 5% of the average 13 591 annual
      prevalent cases. Indigenous patients were more likely to be younger, female, and
      have unknown stroke type. Indigenous prevalence was higher at every age. The age
      standardized prevalence in indigenous men (33.7 per 1000; 95% confidence interval
      31.9-35.4) was 3.7 times greater than in nonindigenous men (9.1 per 1000; 95%
      confidence interval 9.0-9.2). The corresponding estimates for women were 27.1 per
      1000 (25.7-28.4) and 6.1 per 1000 (6.0-6.2) (ratio = 4.4). The percentage with
      selected comorbid conditions was substantially higher for indigenous patients.
      CONCLUSIONS: The high stroke prevalence in indigenous Western Australians,
      coupled with clinical complexity from comorbid conditions, requires access to
      culturally appropriate medical, rehabilitation, and logistical support.
      Intensified primary and secondary prevention is needed to reduce the impact of
      stroke on indigenous people.

PMID- 24725844
TI  - Necrotizing fasciitis caused by Haemophilus influenzae type b in a patient with
      rectal cancer treated with combined bevacizumab and chemotherapy: a case report.
AB  - BACKGROUND: Recently, necrotizing fasciitis has been reported in patients treated
      with bevacizumab, usually secondary to wound healing complications,
      gastrointestinal perforations, or fistula formation. The risk of invasive
      Haemophilus influenzae type b infection is significantly increased in
      immunocompromised hosts. However, necrotizing fasciitis due to Haemophilus
      influenzae type b in a patient treated with combined bevacizumab and chemotherapy
      has not been previously reported. CASE PRESENTATION: A 59-year-old woman was
      admitted to the intensive care unit after sudden onset of fever, chills, and
      right thigh pain. She received chemotherapy with fluorouracil, irinotecan, and
      bevacizumab for colon cancer 10 days prior to admission. The advancing
      erythematous margin and her worsening clinical condition prompted us to suspect
      necrotizing fasciitis and consult the orthopedics department for a fascia biopsy
      and debridement. Surgical exploration revealed a murky dishwater-colored pus
      exudate from the incision site and the lack of a shiny appearance of the fascia
      that also suggested necrotizing fasciitis. After 2 days, the final results of the
      blood and exudate cultures confirmed the presence of Haemophilus influenzae type
      b. A diagnosis of necrotizing fasciitis due to Haemophilus influenzae type b was
      made. The patient required recurrent surgical debridement and drainage, but she
      recovered from the septic shock. CONCLUSIONS: We report a case of necrotizing
      fasciitis due to Haemophilus influenzae type b in a patient without injury and
      with rectal cancer treated with combined bevacizumab and chemotherapy. Physicians
      should consider invasive Haemophilus influenzae type b disease in the presence of
      necrotizing fasciitis in patients treated with this combined treatment modality.

PMID- 24725845
TI  - Healing and shampoo, 1989.

PMID- 24725846
TI  - On the estimation of silent period thresholds in transcranial magnetic
      stimulation.
AB  - OBJECTIVE: We evaluated the induction of corticospinal silent period (SP) using
      transcranial magnetic stimulation (TMS) at stimulation intensities normalized to
      resting motor threshold (rMT) or silent period thresholds (SPTs). The aim was to
      reduce the characteristic inter-individual variation in SP measurements in
      healthy population to improve the sensitivity of such measurements. METHODS: The
      cortical representation area of the right hand musculature of 12 healthy subjects
      was stimulated with navigated TMS with varying stimulating intensities.
      Subsequently, the individual SPTs for eliciting SPs of 20, 30, and 50ms in
      duration were determined from the input-output characteristics. RESULTS: While
      SPT for 20 and 50ms SPs differed from rMT, the SPT for 30ms was similar to rMT.
      Nevertheless, the inter-individual variation in SP duration was reduced
      significantly at 120% of SPT30 when compared with SP durations obtained at 120%
      of rMT. CONCLUSIONS: Inter-individual variation in the SP duration decreases when
      applying TMS at stimulation intensities normalized to the individual SPTs instead
      to the rMT. This makes the SP duration more specific to inhibition and less
      affected by changes in cortical excitability. SIGNIFICANCE: Use of individual
      SPTs may improve the sensitivity of the SP measures in studies with inter
      individual design.

PMID- 24725847
TI  - Bladder filling attenuates spinal cord nociceptive reflexes in humans.
AB  - OBJECTIVE: To examine the viscerosomatic interaction between bladder afferents
      and somatic nociception we evaluated the effect of bladder filling on the
      nociceptive withdrawal reflex (NWR) in 21 healthy subjects. METHODS: NWR was
      evoked in the lower and upper limbs by stimulating the sural and index finger
      digital nerves, respectively, while simultaneously recording EMG activity in the
      biceps femoris and biceps brachialis. NWR pain-related perception was quantified
      on a 10-point pain scale. Bladder filling was evaluated with suprapubic bladder
      sonography. Subjects were examined during empty bladder, medium and high level of
      bladder filling sessions. RESULTS: NWR magnitude in both upper and lower limbs
      and perceived pain for the upper limb were significantly decreased at higher
      levels of bladder filling compared to empty bladder sessions. CONCLUSIONS:
      Reduced NWR magnitude in both upper and lower limbs during bladder filling
      strongly indicates that bladder control and nociception share common modulatory
      descending pathways. Bladder afferents may activate these pathways to suppress
      the micturition reflex, but they may also inhibit spinal reflexes to maintain
      continence during pain stimuli. SIGNIFICANCE: The effect of bladder filling on
      the NWR may represent a useful tool to investigate interactions between the
      neural pathways controlling the bladder and pain.

PMID- 24725849
TI  - A microstructural study of sleep instability in drug-naive patients with
      schizophrenia and healthy controls: sleep spindles, rapid eye movements, and
      muscle atonia.
AB  - This study aimed at characterizing the functional stability of sleep in
      schizophrenia by quantifying dissociated stages of sleep (DSS), and to explore
      their correlation with psychopathology. The sleep of 10 first-break, drug-naive
      young adults with schizophrenia and 10 controls was recorded. Four basic DSS
      patterns were scored: 1) the transitional EEG-mixed intermediate stage (EMIS); 2)
      Rapid-eye-movement (REM) sleep without rapid eye movement (RSWR); 3) REM sleep
      without atonia (RSWA); and 4) non-REM sleep with rapid eye movements. An
      intermediate sleep (IS) score was calculated by summing EMIS and RSWR scores, and
      the durations of intra-REM sleep periods IS (IRSPIS) and IS scored "at the
      expense" of REM sleep (ISERS) were determined. Patients were administered the
      Brief Psychiatric Rating Scale (BPRS) at the time of recording. Proportions of
      each DSS variables over total sleep time and proportions of IRSPIS and ISERS over
      REM sleep duration were compared between patients and controls. Correlation
      coefficients between DSS variables and BPRS total scores were calculated. The
      proportion of total DSS did not differ between patients and controls. Among DSS
      subtypes, RSWA was significantly increased in patients while other comparisons
      showed no significant differences. Significant positive correlations were found
      between BPRS scores and proportions of DSS, IS, RSWR, IRSPIS and ISERS over total
      sleep and REM sleep durations. These results demonstrate the functional
      instability of REM sleep in first-break, drug naive young adults with
      schizophrenia and unveil a pattern reminiscent of REM sleep behavior disorder.
      The significant correlation suggests that schizophrenia and REM sleep share
      common neuronal control mechanisms. 

PMID- 24725848
TI  - A simple breathing circuit allowing precise control of inspiratory gases for
      experimental respiratory manipulations.
AB  - BACKGROUND: Respiratory manipulations modulating blood flow and oxygenation
      levels have become an important component of modern functional MRI applications.
      Manipulations often consist of temporarily switching inspired fractions of CO2
      and O2; and have typically been performed using simple oxygen masks intended for
      applications in respiratory therapy. However, precise control of inspired gas
      composition is difficult using this type of mask due to entrainment of room air
      and resultant dilution of inspired gases. We aimed at developing a gas delivery
      apparatus allowing improved control over the fractional concentration of inspired
      gases, to be used in brain fMRI studies. FINDINGS: The breathing circuit we have
      conceived allowed well controlled step changes in FiO2 and FiCO2, at moderate
      flow rates achievable on standard clinical flow regulators. In a two run test
      inside the scanner we demonstrate that tightly controlled simple gas switching
      manipulations can afford good intra-subject reproducibility of induced
      hyperoxia/hypercapnia responses. Although our approach requires a non-vented mask
      fitting closely to the subject's face, the circuit ensures a continuous supply of
      breathable air even if the supply of medical gases is interrupted, and is easily
      removable in case of an emergency. The apparatus we propose is also compact and
      MRI compatible, allowing subject placement in confined spaces such as an MRI
      scanner for brain examinations. CONCLUSIONS: We have reported a new approach for
      the controlled administration of medical gases, and describe an implementation of
      the breathing circuit that is MRI compatible and uses commercially available
      parts. The resultant apparatus allows simple, safe and precise manipulations of
      FiO2 and FiCO2.

PMID- 24725850
TI  - Long-term course of cognitive function in chronically hospitalized patients with
      schizophrenia transitioning to community-based living.
AB  - Schizophrenia is associated with impairments in social interactions, and the
      conditions under which patients live and undergo treatment appear to have an
      important role in the course of the disease. However, the influences of care
      settings on the course of cognition remain controversial. The closure of
      psychiatric hospitals and the transition to community-based living is a golden
      opportunity to address this issue. The aims of the present study were to examine
      (1) the longitudinal course of cognition as well as the psychopathology and
      social functioning of schizophrenia patients who had been chronically
      hospitalized and then discharged, and (2) the key cognitive predictors of the
      functional outcome of such patients. Seventy-eight patients were transferred to
      the community after the closure of a psychiatric hospital. These patients were
      followed-up for 5 years and underwent annual examinations that included measures
      of cognition, psychiatric symptoms, and social functioning. Fifty-six patients
      completed all the assessments. Although consistent improvements were shown in the
      cognitive domains for attention and memory, the initial improvements in global
      cognition and processing speed ultimately began to decline. Symptoms and global
      functioning improved almost consistently over the course of the follow-up period.
      Stepwise multiple regressions revealed category fluency at baseline predicted
      social functioning at 5 years. However, this correlation was no longer
      significant when psychopathological variables were included as predictors. These
      results suggest that care settings affect the course of cognition, and addressing
      these conditions may lead to a certain degree of cognitive improvement even among
      schizophrenia patients who have been chronically institutionalized.

PMID- 24725851
TI  - N-acetylcysteine prevents increased amphetamine sensitivity in social isolation
      reared mice.
AB  - Treating individuals at risk to develop schizophrenia may be strategic to delay
      or prevent transition to psychosis. We verified the effects of N-acetylcysteine
      (NAC) in a neurodevelopmental model of schizophrenia. C57 mice were reared in
      isolation or social groups and treated with NAC from postnatal day 42-70; the
      locomotor response to amphetamine was assessed at postnatal day 81. NAC treatment
      in isolated mice prevented the hypersensitivity to amphetamine, suggesting
      neuroprotection relevant to striatal dopamine. Considering its safety and
      tolerability profile, complementary studies are warranted to further evaluate the
      usefulness of NAC to prevent conversion to schizophrenia in at-risk individuals. 

PMID- 24725852
TI  - [Comments about the presurgical administration of intravenous iron].

PMID- 24725853
TI  - [Relationship between cystatin C and coronary artery calcification in patients
      with intermediate cardiovascular risk].
AB  - BACKGROUND AND OBJECTIVE: Cardiovascular disease is the leading cause of
      morbimortality in industrialized countries. Quantification of coronary artery
      calcium (CAC) has been shown to have an independent and incremental prognostic
      value over traditional risk factors for the prediction of mortality and
      cardiovascular events. The aim of our study was to determine the possible
      relationship between CAC and cystatin C (CTC). PATIENTS AND METHOD: We included
      104 patients with stable chest pain, free of cardiovascular disease and
      nephropathy, with intermediate cardiovascular risk. Both CAC (Agatston) and CTC
      were determined. RESULTS: CTC was independently associated with the CAC level and
      the presence of coronary disease. CONCLUSIONS: CTC values may be associated with
      CAC and coronary disease. Further studies are needed to know the importance of
      these markers in clinical practice.

PMID- 24725854
TI  - [Alternative splicing regulation: implications in cancer diagnosis and
      treatment].
AB  - The accurate expression of the genetic information is regulated by processes like
      mRNA splicing, proposed after the discoveries of Phil Sharp and Richard Roberts,
      who demonstrated the existence of intronic sequences, present in almost every
      structural eukaryotic gene, which should be precisely removed. This intron
      removal is called "splicing", which generates different proteins from a single
      mRNA, with different or even antagonistic functions. We currently know that
      alternative splicing is the most important source of protein diversity, given
      that 70% of the human genes undergo splicing and that mutations causing defects
      in this process could originate up to 50% of genetic diseases, including cancer.
      When these defects occur in genes involved in cell adhesion, proliferation and
      cell cycle regulation, there is an impact on cancer progression, rising the
      opportunity to diagnose and treat some types of cancer according to a particular
      splicing profile. 

PMID- 24725855
TI  - [Persistent polyclonal B lymphocytosis].

PMID- 24725856
TI  - [Psychometric validation of the OAB-V8 and OAB-V3 scales for the screening of
      patients with probable overactive bladder in the Spanish population].
AB  - BACKGROUND AND OBJECTIVE: To perform the psychometric validation in the Spanish
      population of the Overactive Bladder Awareness Tool (OAB-V8) scale and its
      abbreviated version OAB-V3 for screening patients with probable overactive
      bladder (OAB). PATIENTS AND METHODS: A cross-sectional study was conducted in a
      population aged over 18 years, which was representative of the prevalence of OAB
      in Spain using an online methodology (Internet survey). Psychometric properties
      included feasibility, reliability, and validity. Subjects were classified
      according to the likelihood of OAB, using an automated algorithm validated
      previously. ROC curve analysis was performed, and the sensitivity, specificity,
      and positive and negative predictive values were also assessed. RESULTS: A total
      of 2,035 subjects with a mean+SD age of 52.7+12.1 years were included (50.8%)
      men. In total 13.7% were classified as "Probable", 27.9% "Possible", and 58.3%
      "No" OAB. The internal consistency of both OAB-V8 and OAB-V3 scales was high
      (0.894 and 0.851, respectively). The item-total correlation coefficients were
      high; 0.87-0.88 and 0.71-0.83, respectively. Intraclass correlation coefficient
      for OAB-V8 was 0.826 (confidence interval 95% 0.695-0.901) and it was 0.828
      (confidence interval 0.623-0.922) for OAB-V3. The optimum cut-off value of OAB-V8
      for detecting probable OAB was>=8 points (AUC=0.895, sensitivity 0.875,
      specificity 0.735), while for the OAB-V3 it was >= 3 (AUC=0.910, sensitivity
      0.828, specificity 0.825). CONCLUSION: Both OAB-V8 and OAB-V3 scales were
      considered useful online self-administered screening tools, which were also
      feasible, reliable and valid for the detection of patients with probable OAB in
      the general population in Spain.

PMID- 24725857
TI  - Graphene oxide-silica composite coating hollow fiber solid phase microextraction
      online coupled with inductively coupled plasma mass spectrometry for the
      determination of trace heavy metals in environmental water samples.
AB  - In this work, a novel graphene oxide-silica (GO-silica) composite coating was
      prepared for hollow fiber solid phase microextraction (HF-SPME) of trace Mn, Co,
      Ni, Cu, Cd and Pb followed by on-line inductively coupled plasma mass
      spectrometry (ICP-MS) detection. The structure of the prepared graphene oxide and
      GO-silica composite was studied and elucidated by atomic force microscopy (AFM),
      transmission electron microscopy (TEM), Fourier transform infrared spectroscopy
      (FT-IR) and X-ray photoelectron spectroscopy (XPS). The GO-silica composite
      coated hollow fiber was characterized by scanning electron microscope (SEM), and
      the results show that the GO-silica composite coating possessed a homogeneous and
      wrinkled structure. Various experimental parameters affecting the extraction of
      the target metal ions by GO-silica composite coated HF-SPME have been
      investigated carefully. Under the optimum conditions, the limits of detection
      (LODs, 3sigma) for Mn, Co, Ni, Cu, Cd and Pb were 7.5, 0.39, 20, 23, 6.7 and 28
      ng L(-1) and the relative standard deviations (RSDs, c(Mn, Co, Cd)=0.05 MUg L(
      1), c(Ni, Cu, Pb)=0.2 MUg L(-1), n=7) were 7.2, 7.0, 5.6, 7.3, 7.8 and 4.6%,
      respectively. The accuracy of the proposed method was validated by the analysis
      of Certified Reference Material of GSBZ 50009-88 environmental water and the
      determined values were in a good agreement with the certified values. The
      proposed method has been successfully applied for the determination of trace
      metals in real environmental water samples with recoveries ranging from 85 to
      119%.

PMID- 24725858
TI  - Development and validation of an analytical method for the separation and
      determination of major bioactive curcuminoids in Curcuma longa rhizomes and
      herbal products using non-aqueous capillary electrophoresis.
AB  - A simple, fast and efficient non-aqueous capillary electrophoresis method (NACE)
      was developed for the simultaneous determination of three major bioactive
      curcuminoids (CMNs) in Curcuma longa rhizomes and its herbal products. Good
      separation, resolution and reproducibility were achieved with the background
      electrolyte (BGE) consisting a mixture of 15.0 mM sodium tetraborate and 7.4 mM
      sodium hydroxide (NaOH) in 2:10:15 (v/v/v) of water, 1-propanol, and methanol.
      The influences of background electrolyte, sodium hydroxide, water, sodium dodecyl
      sulfate and hydroxylpropyl-beta-cyclodextrin on separations were investigated.
      The separation was carried out in a fused-silica capillary tube with reverse
      polarity. Hydrodynamic injection of 25mbar for 12s was used for injecting samples
      and a voltage of 28 kV was applied for separation. The ultrasonication method was
      used for the extraction of CMNs from the turmeric herbal products and the extract
      was filtered and directly injected without any further treatments. The limits of
      detection and quantification were less than 5.0 and 14.6 ug/ml respectively for
      all CMNs. The percentage recoveries for CMNs were >97.2% (%RSD, <2.62). The
      results obtained by the method were compared with existing spectrophotometric and
      HPLC methods. The related compounds in the extract did not interfere in the
      determination of CMNs. The proposed NACE method is better than existing
      chromatographic and electrophoretic methods in terms of simple electrophoretic
      medium, fast analysis and good resolution.

PMID- 24725859
TI  - Multiwalled carbon nanotubes-doped polymeric ionic liquids coating for multiple
      headspace solid-phase microextraction.
AB  - Multiple headspace solid-phase microextraction (SPME) has proved high efficiency
      in analysis of volatile compounds in complex samples. Fibers used in multiple
      headspace SPME must provide a logarithm relationship between peak areas and
      extraction times. The aim of this work was to investigate the potential of a
      carbon nanotube doped-polymeric ionic liquid (PILs) fiber for multiple headspace
      SPME of 2-naphthol in fruit samples, using gas chromatography (GC) for analysis.
      Based on theory of multiple headspace SPME, beta parameters of fruit and aqueous
      samples were obtained and used for quantitation. The interference effects of
      sample matrix on proposed multiple headspace SPME method were investigated and
      compared with that of headspace SPME by determination of significant differences
      (P) of peak areas. It showed high independence from matrix effects. The proposed
      multiple headspace SPME-GC method also exhibited high repeatability (relative
      standard deviation of 2.56%) and recoveries (81.9-110%) for the analysis of real
      samples. 

PMID- 24725860
TI  - Response surface methodology based on central composite design as a chemometric
      tool for optimization of dispersive-solidification liquid-liquid microextraction
      for speciation of inorganic arsenic in environmental water samples.
AB  - Dispersive-solidification liquid-liquid microextraction (DSLLME) coupled with
      electrothermal atomic absorption spectrometry (ETAAS) was developed for
      preconcentration and determination of inorganic arsenic (III, V) in water
      samples. At pH=1, As(III) formed complex with ammonium pyrrolidine
      dithiocarbamate (APDC) and extracted into the fine droplets of 1-dodecanol
      (extraction solvent) which were dispersed with ethanol (disperser solvent) into
      the water sample solution. After extraction, the organic phase was separated by
      centrifugation, and was solidified by transferring into an ice bath. The
      solidified solvent was transferred to a conical vial and melted quickly at room
      temperature. As(III) was determined in the melted organic phase while As(V)
      remained in the aqueous layer. Total inorganic As was determined after the
      reduction of the pentavalent forms of arsenic with sodium thiosulphate and
      potassium iodide. As(V) was calculated by difference between the concentration of
      total inorganic As and As(III). The variable of interest in the DSLLME method,
      such as the volume of extraction solvent and disperser solvent, pH, concentration
      of APDC (chelating agent), extraction time and salt effect, was optimized with
      the aid of chemometric approaches. First, in screening experiments, fractional
      factorial design (FFD) was used for selecting the variables which significantly
      affected the extraction procedure. Afterwards, the significant variables were
      optimized using response surface methodology (RSM) based on central composite
      design (CCD). In the optimum conditions, the proposed method has been
      successfully applied to the determination of inorganic arsenic in different
      environmental water samples and certified reference material (NIST RSM 1643e). 

PMID- 24725861
TI  - Optimization and validation of an automated DHS-TD-GC-MS method for the
      determination of aromatic esters in sweet wines.
AB  - A dynamic headspace sorptive extraction (DHS) combined with thermal desorption
      (TD) and coupled with gas chromatography-mass spectrometry (GC/MS) was developed
      for the determination of 11 esters which contribute to the fruity aroma in sweet
      wines. A full factorial (4 factors, 2 level) experiment design was used to
      optimize the extraction conditions and the results were evaluated by multiple
      linear regression (MLR) and principal component analysis (PCA). The esters showed
      optimal extraction using an extraction temperature of 30 degrees C during 20 min,
      and a subsequent purge volume of 300 mL and dry volume of 50 mL. Afterwards,
      quantification was achieved using calibration curves constructed for each ester
      with linear regression equations having correlation coefficients (R(2)) ranging
      from 0.9894 to 0.9981. The proposed method was successfully validated and showed
      good intermediate precision, repeatability and accuracy values for all the
      monitored compounds. Finally, the method was applied to quantify esters, with
      fruity aromatic notes, of sweet white and red wines, elaborated with different
      winemaking processes.

PMID- 24725862
TI  - Large volume injection in gas chromatography using the through oven transfer
      adsorption desorption interface operating under vacuum.
AB  - The present work describes a modification of the Through Oven Transfer Adsorption
      Desorption (TOTAD) interface, consisting of coupling a vacuum system to reduce
      the consumption of the helium needed to totally remove the eluent for large
      volume injection (LVI) in gas chromatography (GC). Two different retention
      materials in the liner of the TOTAD interface were evaluated: Tenax TA, which was
      seen to be unsuitable for working under vacuum conditions, and
      polydimethylsiloxane (PDMS), which provided satisfactory repeatability as well as
      a good sensitivity. No variability was observed in the retention times in either
      case. Solutions containing organophosphorous pesticides in two different
      solvents, a polar (methanol/water) and a non-polar (hexane) solvent, were used to
      evaluate the modification. The vacuum system coupled to the TOTAD interface
      allowed up to 90% helium to be saved without affecting the performance. 

PMID- 24725863
TI  - New multilayer coating using quaternary ammonium chitosan and kappa-carrageenan
      in capillary electrophoresis: application in fast analysis of betaine and
      methionine.
AB  - The aim of this study was to develop a new multilayer coating with crosslinked
      quaternary ammonium chitosan (hydroxypropyltrimethyl ammonium chloride chitosan;
      HACC) and kappa-carrageenan for use in capillary electrophoresis. A new semi
      permanent multilayer coating was formed using the procedure developed and the
      method does not require the presence of polymers in the background electrolyte
      (BGE). The new capillary multilayer coating showed a cathodic electroosmotic flow
      (EOF) of around 30*10(-9) m(2) V(-1) s(-1) which is pH-independent in the range
      of pH 2 to 10. The enhanced EOF at low pH obtained contributed significantly to
      the development of a fast method of separation. The multilayer coating was then
      applied in the development of a fast separation method to determine betaine and
      methionine in pharmaceutical formulations by capillary zone electrophoresis
      (CZE). The BGE used to determine the betaine and methionine concentrations was
      composed of 10 mmol L(-1) tris(hydroxymethyl) aminomethane, 40 mmol L(-1)
      phosphoric acid and 10% (v/v) ethanol, at pH 2.1. A fused-silica capillary of 32
      cm (50 um ID*375 um OD) was used in the experiments and samples and standards
      were analyzed employing the short-end injection procedure (8.5 cm effective
      length). The instrumental analysis time of the optimized method was 1.53 min
      (approx. 39 runs per hour). The validation of the proposed method for the
      determination of betaine and methionine showed good linearity (R(2)>0.999),
      adequate limit of detection (LOD <8 mg L(-1)) for the concentration in the
      samples and inter-day precision values lower than 3.5% (peak area and time
      migration). The results for the quantification of the amino acids in the samples
      determined by the CZE-UV method developed were statistically equal to those
      obtained with the comparative LC-MS/MS method according to the paired t-test with
      a confidence level of 95%.

PMID- 24725864
TI  - Morphological, spectral and chromatography analysis and forensic comparison of
      PET fibers.
AB  - Poly(ethylene terephthalate) (PET) fiber analysis and comparison by spectral and
      polymer molecular weight determination was investigated. Plain fibers of PET, a
      common textile fiber and plastic material was chosen for this study. The fibers
      were analyzed for morphological (SEM and AFM), spectral (IR and NMR), thermal
      (DSC) and molecular weight (MS and GPC) differences. Molecular analysis of PET
      fibers by Gel Permeation Chromatography (GPC) allowed the comparison of fibers
      that could not be otherwise distinguished with high confidence. Plain PET fibers
      were dissolved in hexafluoroisopropanol (HFIP) and analyzed by GPC using
      hexafluoroisopropanol:chloroform 2:98 v/v as eluent. 14 PET fiber samples,
      collected from various commercial producers, were analyzed for polymer molecular
      weight by GPC. Distinct differences in the molecular weight of the different
      fiber samples were found which may have potential use in forensic fiber
      comparison. PET fibers with average molecular weights between about 20,000 and
      70,000 g mol(-1) were determined using fiber concentrations in HFIP as low as 1
      MUg mL(-1). This GPC analytical method can be applied for exclusively distinguish
      between PET fibers using 1 MUg of fiber. This method can be extended to forensic
      comparison of other synthetic fibers such as polyamides and acrylics.

PMID- 24725865
TI  - Porous molecularly imprinted monolithic capillary column for on-line extraction
      coupled to high-performance liquid chromatography for trace analysis of
      antimicrobials in food samples.
AB  - A novel porous molecularly imprinted monolithic capillary column (MIMCC) based on
      ternary porogen was synthesized by in situ technique with sulfaquinoxaline as the
      template molecule. The characteristics of the MIMCC were investigated by scanning
      electron microscopy, infrared spectrum, thermogravimetric analysis and solvent
      resistance test. The saturated adsorption amount of sulfaquinoxaline on MIMCC was
      2.7 times over that on the non-imprinted monolithic capillary column (NIMCC). The
      MIMCC also exhibited good enrichment ability to its analogs and the enrichment
      factors were 46-211 for five antimicrobials. High permeability and imprinting
      factors as well as good stability, reproducibility and long lifetime were
      obtained. An on-line method based on MIMCC solid-phase microextraction coupled
      with high-performance liquid chromatography was developed for the determination
      of trace antimicrobials in complex samples. The good linearity for
      sulfametoxydiazine, sulamethoxazole and sulfaquinoxaline was 0.05-10 ug/L, the
      limits of detection (LODs) were 10.0-14.0 ng/L. The linear range for mequindox
      and quinocetone were 0.10-10.0 ug/L, the LODs were 20.0-27.0 ng/L respectively.
      The recoveries were 71.0-108.2% with relative standard deviation of 1.6-8.5%,
      correspondingly. The results showed that MIMCC could effectively enrich
      antimicrobials from complex matrices. The on-line method based on MIMCC and HPLC
      was selective, sensitive and convenient for trace determination of antimicrobials
      in complex samples.

PMID- 24725866
TI  - Simultaneous in situ derivatization and ultrasound-assisted dispersive magnetic
      solid phase extraction for thiamine determination by spectrofluorimetry.
AB  - A simple and rapid method for the simultaneous in situ derivatizaion,
      preconcentration and extraction of thiamine (vitamin B1) as a model analyte was
      developed by a novel quantitative method, namely ultrasound-assisted dispersive
      magnetic solid phase extraction spectrofluorimetry (USA-DMSPE-FL) from different
      real samples. This method consists of sample preparation, in situ derivatization,
      exhaustive extraction and clean up by a single process. High extraction
      efficiency and in situ derivatization in a short period of time is the main
      advantages of this procedure. For this purpose, the reusable magnetic multi-wall
      carbon nanotube (MMWCNT) nanocomposite was used as an adsorbent for
      preconcentration and determination of thiamine. Thiamine was, simultaneously, in
      situ derivatized as thiochrome by potassium hexacyanoferrate (III) and adsorbed
      on MMWCNT in an ultrasonic water bath. The MMWCNTs were then collected using an
      external magnetic field. Subsequently, the extracted thiochrome was washed from
      the surface of the adsorbent and determined by spectrofluorimetry. The developed
      method, which has been analytically characterized under its optimal operating
      conditions, allows the detection of the analyte in the samples with method
      detection limits of 0.37 ug L(-1). The repeatability of the method, expressed as
      the relative standard deviation (RSD, n=6), varies between 2.0% and 4.8% in
      different real samples, while the enhancement factor is 197. The proposed
      procedure has been applied for the determination of thiamine in biological (serum
      and urine), pharmaceutical (multivitamin tablet and B complex syrup) and
      foodstuff samples (cereal, wheat flour, banana and honey) with the good
      recoveries in the range from 90% to 105%.

PMID- 24725867
TI  - Headspace-gas chromatographic fingerprints to discriminate and classify
      counterfeit medicines.
AB  - Counterfeit medicines are a global threat to public health. These pharmaceuticals
      are not subjected to quality control and therefore their safety, quality and
      efficacy cannot be guaranteed. Today, the safety evaluation of counterfeit
      medicines is mainly based on the identification and quantification of the active
      substances present. However, the analysis of potential toxic secondary
      components, like residual solvents, becomes more important. Assessment of
      residual solvent content and chemometric analysis of fingerprints might be useful
      in the discrimination between genuine and counterfeit pharmaceuticals. Moreover,
      the fingerprint approach might also contribute in the evaluation of the health
      risks different types of counterfeit medicines pose. In this study a number of
      genuine and counterfeit Viagra((r)) and Cialis((r)) samples were analyzed for
      residual solvent content using headspace-GC-MS. The obtained chromatograms were
      used as fingerprints and analyzed using different chemometric techniques:
      Principal Component Analysis, Projection Pursuit, Classification and Regression
      Trees and Soft Independent Modelling of Class Analogy. It was tested whether
      these techniques can distinguish genuine pharmaceuticals from counterfeit ones
      and if distinct types of counterfeits could be differentiated based on health
      risks. This chemometric analysis showed that for both data sets PCA clearly
      discriminated between genuine and counterfeit drugs, and SIMCA generated the best
      predictive models. This technique not only resulted in a 100% correct
      classification rate for the discrimination between genuine and counterfeit
      medicines, the classification of the counterfeit samples was also superior
      compared to CART. This study shows that chemometric analysis of headspace-GC
      impurity fingerprints allows to distinguish between genuine and counterfeit
      medicines and to differentiate between groups of counterfeit products based on
      the public health risks they pose. 

PMID- 24725868
TI  - Structural characterization of cyclosporin A, C and microbial bio-transformed
      cyclosporin A analog AM6 using HPLC-ESI-ion trap-mass spectrometry.
AB  - Cyclosporin A (CyA), a cyclic undecapeptide produced by a number of fungi,
      contains 11 unusual amino acids, and has been one of the most commonly prescribed
      immunosuppressive drugs. To date, there are over sixty different analogs reported
      as congeners and analogs resulting from precursor-directed biosynthesis, human
      CYP-mediated metabolites, or microbial bio-transformed analogs. However, there is
      still a need for more structurally diverse CyA analogs in order to discover new
      biological potentials and/or improve the physicochemical properties of the
      existing cyclosporins. As a result of the complexity of the resulting mass
      spectrometric (MS) data caused by its unusual amino acid composition and its
      cyclic nature, structural characterization of these cyclic peptides based on
      fragmentation patterns using multiple tandem MS analyses is challenging task.
      Here, we describe, an efficient HPLC-ESI-ion trap MS(n) (up to MS(8)) was
      developed for the identification of CyA and CyC, a (Thr(2))CyA congener in which
      L-aminobutyric acid (Abu) is replaced by L-threonine (Thr). In addition, we
      examined the fragmentation patterns of a CyA analog obtained from the cultivation
      of a recombinant Streptomyces venezuelae strain fed with CyA, assigning this
      analog as (gamma-hydroxy-MeLeu(6))CyA (otherwise, known as an human CYP
      metabolite AM6). This is the first report on both the MS(n)-aided identification
      of CyC and the structural characterization of a CyA analog by employing HPLC-ESI
      ion trap MS(n) analysis.

PMID- 24725869
TI  - Fluorescence determination of acrylamide in heat-processed foods.
AB  - A simple and rapid fluorescence method has been developed for the determination
      of acrylamide in heat-processed food samples. In the determination, acrylamide is
      degraded through Hofmann reaction to generate vinyl amine, and pyrrolinone is
      produced when the vinyl amine reacts with fluorescamine, resulting in a strong
      fluorescence emission at 480 nm. Hofmann reaction is a key step for the
      fluorescence determination of acrylaminde, and the reaction conditions are
      investigated and optimized. Under the optimal conditions, the fluorescence
      intensity increases with the increase of acrylamide concentrations. The linear
      range between the fluorescence intensity and the square-root of acrylamide
      concentrations is from 0.05 MUg mL(-1) to 20 MUg mL(-1) with the correlation
      coefficient R(2)=0.9935. The detection limit is 0.015 MUg mL(-1) and the recovery
      for food samples is from 66.0% to 110.6%. In comparison with Specification of
      Entry&Exit Inspection and Quarantine Bureau of The People's Republic of China
      (SN/T 2281-2009), the method showed comparable results and demonstrated the
      accuracy of the method.

PMID- 24725870
TI  - Fe3O4@rGO doped molecularly imprinted polymer membrane based on magnetic field
      directed self-assembly for the determination of amaranth.
AB  - Based on magnetic field directed self-assembly (MDSA) of Fe3O4@rGO composites, a
      novel magnetic molecularly imprinted electrochemical sensor (MIES) was fabricated
      and developed for the determination of the azo dye amaranth. Fe3O4@rGO composites
      were obtained by a one-step approach involving the initial intercalating of iron
      ions between the graphene oxide layers via the electrostatic interaction,
      followed by the reduction with hydrazine hydrate to deposit Fe3O4 nanoparticles
      onto the reduced oxide graphene nanosheets. In molecular imprinting, the complex
      including the function monomer of aniline, the template of amaranth and Fe3O4@rGO
      was pre-assembled through pi-pi stacking and hydrogen bonding interactions, and
      then was self-assembled on the surface of magnetic glassy carbon electrode (MGCE)
      with the help of magnetic field induction before electropolymerization. The
      structures and morphologies of Fe3O4@rGO and the doped molecularly imprinted
      polymers (MIPs) were investigated by Fourier transform infrared spectrometer (FT
      IR), Raman spectra and scanning electron microscope (SEM). Besides, the
      characterization by differential pulse voltammetry (DPV) showed that Fe3O4@rGO
      composites promoted the electrical conductivity of the imprinted sensors when
      doped into the MIPs. The adsorption isotherms and adsorption kinetics were
      employed to evaluate the performances of MIES. The detection of amaranth was
      achieved via the redox probe K3[Fe(CN)6] by blocking the imprinted cavities,
      which avoided the interferences of oxidation products and analogs of amaranth.
      Furthermore, the prepared MIES exhibited good sensitivity, selectivity,
      reproducibility and efficiency for detecting amaranth in fruit drinks. The
      average recoveries were 93.15-100.81% with the RSD <3.0%. 

PMID- 24725871
TI  - Conducting polymer coated single-walled carbon nanotube gas sensors for the
      detection of volatile organic compounds.
AB  - The current work involves fabrication, characterization and subsequent evaluation
      of poly(3,4-ethylenedioxythiophene) doped with poly(styrene sulfonic acid)
      (PEDOT:PSS) coated single walled carbon nanotubes (SWNTs) sensors for detecting
      analytes of interest in industrial manufacturing. By varying the conducting
      polymer's synthesis conditions in terms of charge controlled
      electropolymerization of the monomer EDOT in presence of the dopant PSS, the
      sensing performance of the PEDOT:PSS functionalized SWNT sensors was
      systematically optimized. Electrical characterization in terms of change in
      resistance, cyclic voltammetry and field-effect transistor measurements was
      performed to confirm the presence of PEDOT:PSS coating on SWNTs. The optimized
      sensors exhibited sensing properties over a wide dynamic range of concentrations
      towards saturated vapors of volatile organic compounds (VOCs) such as methanol,
      ethanol and methyl ethyl ketone (MEK) at room temperature. The limit of detection
      of this sensor was found to be 1.3%, 5.95% and 3% for saturated vapors of
      methanol, ethanol and methyl ethyl ketone (MEK) respectively. In terms of
      performance, when compared with bare SWNTs, these hybrid sensors exhibited better
      sensitivity. The underlying mechanism of sensing was also investigated by using
      them in chemFET mode of sensor configuration. 

PMID- 24725872
TI  - Ultra-performance liquid chromatography coupled with graphene/polyaniline
      nanocomposite modified electrode for the determination of sulfonamide residues.
AB  - An ultra-performance liquid chromatography (UPLC) coupled with
      graphene/polyaniline (G/PANI)-modified screen-printed carbon electrode was
      developed for separation and sensitive determination of eight sulfonamides (SAs)
      in shrimp. Electrospraying was selected for electrode modification because it can
      generate the well dispersion of G/PANI nanocomposites on the electrode surface.
      Prior to electrochemical detection, eight SAs were completely separated within 7
      min by using reversed phase UPLC (C4) with mobile phase containing 70:25:5
      (v/v/v) of potassium hydrogen phosphate (pH 3):acetonitrile:ethanol. For
      amperometric detection, the detection potential acquired from hydrodynamic
      voltammetry was found to be +1.4V. Under optimal conditions, a wide linearity and
      low limit of detection were obtained for eight SAs in the range of 0.01-10 ug mL(
      1) and 1.162-6.127 ng mL(-1), respectively. Compared to boron-doped diamond (BDD)
      electrode, a G/PANI-modified screen-printed carbon electrode offered higher
      sensitivity with lower operating cost. To determine SAs in shrimp samples, solid
      phase extraction was used to clean up and preconcentrate the samples prior to
      UPLC separation. To validate this developed method, a highly quantitative
      agreement was accomplished with UPLC-UV system. Thus, this proposed system might
      be an alternative approach for rapid, inexpensive, and sensitive determination of
      SAs in shrimps.

PMID- 24725873
TI  - The influence of inorganic salts with chaotropic properties on the
      chromatographic behavior of ropinirole and its two impurities.
AB  - Chaotropic agents recently gained popularity as interesting and useful mobile
      phase additives in liquid chromatography due to their effect on analytes
      retention, peak symmetry and separation efficiency. They mimic the role of
      classical ion-pairing agents, but with less drawbacks, so their use becomes
      attractive in the field of pharmaceutical analysis. In this paper, the influence
      of sodium trifluoroacetate and sodium perchlorate on the chromatographic behavior
      of ropinirole and its impurities is examined. By the extended thermodynamic
      approach, it was shown that the separation in the given system was predominantly
      governed by electrostatic interactions between the protonated analytes and the
      charged surface of the stationary phase, but the ion-pair complex formation in
      the eluent also proved to be significant. Further, the employment of face
      centered central composite design enabled the understanding of the effect of
      chaotropic agent concentration and its interactions with other factors
      (acetonitrile content and pH of the water phase) that influence the given
      chromatographic system. Finally, the same data was used for multi-objective
      optimization based on the grid point search method. After the method validation,
      the adequacy of the suggested approach in development of methods for routine
      pharmaceutical analysis was proven. 

PMID- 24725874
TI  - Characterization of newfound natural luminescent properties of melamine, and
      development and validation of a method of high performance liquid chromatography
      with fluorescence detection for its determination in kitchen plastic ware.
AB  - Experimental studies of the natural photoluminescence of melamine in aqueous
      solutions showed that its fluorescence intensity (at 250/365 nm) was appropriated
      for analytical purposes. The exploitation of such melamine property provided the
      basis of development of a new, simple, precise and accurate method based on high
      performance liquid chromatography with fluorescence detection (HPLC-Fluo) to
      determine melamine in kitchen plastic ware following aqueous extraction using a
      microwave oven. Optimization of analytical parameters such as solvent
      composition, pH and extraction conditions led to limits of detection and
      quantification of melamine of 0.0081 and 0.027 MUg mL(-1), respectively, with a
      linear range up to 10 MUg mL(-1). Sample extracts fortified with melamine at
      three concentration levels produced an average recovery of 98+/-6%, which was in
      agreement with the results achieved with a reference HPLC-UV method. Different
      samples of kitchen plastic ware analyzed by the developed and optimized method
      showed melamine concentrations in the aqueous extract up to 17 ug mL(-1), which
      corresponded to 86.0 mg kg(-1) in these utensils. The results obtained indicate
      that the use of kitchen plastic ware made of melamine can contaminate food with
      this compound after heating in a microwave oven.

PMID- 24725875
TI  - Confocal Raman spectroscopy to trace lipstick with their smudges on different
      surfaces.
AB  - Lipsticks are very popular cosmetic products that can be transferred by contact
      to different surfaces, being important forensic evidence with an intricate
      analysis if they are found in a crime scene. This study evaluates the use of
      confocal Raman microscopy at 780 nm excitation wavelength for the nondestructive
      identification of 49 lipsticks of different brands and colors, overcoming the
      lipstick fluorescence problem reported by previous works using other laser
      wavelengths. Although the lipsticks samples showed some fluorescence, this effect
      was not so intense to completely overwhelm the Raman spectra. Lipsticks smudges
      on twelve different surfaces commonly stained with these samples were also
      analyzed. In the case of the surfaces, some of them provided several bands to the
      smudge spectra compromising the identification of the lipstick. For these samples
      spectral subtraction of the interfering bands from the surface was performed.
      Finally, five different red lipsticks with very similar color were measured on
      different surfaces to evaluate the lipstick traceability with their smudges even
      on interfering surfaces. Although previous spectral subtraction was needed in
      some cases, all the smudged were linked to their corresponding lipsticks even
      when they are smeared on the interfering surfaces. As a consequence, confocal
      Raman microscopy using the 780 nm excitation laser is presented as a
      nondestructive powerful tool for the identification of these tricky samples.

PMID- 24725876
TI  - The method for on-site determination of trace concentrations of methyl mercaptan
      and dimethyl sulfide in air using a mobile mass spectrometer with atmospheric
      pressure chemical ionization, combined with a fast enrichment/separation system.
AB  - A method for fast simultaneous on-site determination of methyl mercaptan and
      dimethyl sulfide in air was developed. The target compounds were actively
      collected on silica gel, followed by direct flash thermal desorption, fast
      separation on a short chromatographic column and detection by means of mass
      spectrometer with atmospheric pressure chemical ionization. During the sampling
      of ambient air, water vapor was removed with a Nafion selective membrane. A
      compact mass spectrometer prototype, which was designed earlier at Trofimuk
      Institute of Petroleum Geology and Geophysics, was used. The minimization of gas
      load of the atmospheric pressure ion source allowed reducing the power
      requirements and size of the vacuum system and increasing its ruggedness. The
      measurement cycle is about 3 min. Detection limits in a 0.6 L sample are 1 ppb
      for methyl mercaptan and 0.2 ppb for dimethyl sulfide.

PMID- 24725877
TI  - Analytical evaluation of a high-throughput enzyme-linked immunosorbent assay for
      acrylamide determination in fried foods.
AB  - The analytical performance and evaluation of a kit-based ELISA for the
      determination of acrylamide in fried potato and corn chip samples are described.
      The sample homogenate is subjected to clean-up using SPE, followed by analyte
      derivatization and ELISA detection. Accuracy, precision and linearity of the
      ELISA procedure have been validated using spiked samples. Analytical recovery
      ranged from 91.8% to 96.0% with coefficients of variation below 15%. Good
      linearity over a wide range of dilution and minimal assay drift was observed
      within a microtiter plate. IC50 value of the calibration curve was 110 ng/mL,
      with the limit of detection about 5 ng/mL and dynamic range from 10 to 1000
      ng/mL. The high specificity of the ELISA was demonstrated by cross-reactivity
      study using 11 potential cross-reactants. A good correlation between the results
      obtained from the ELISA and GC-MS within the concentration range 120-1500 MUg/kg
      was found in the chip samples (r=0.992, n=120). The data demonstrate that the
      evaluated and validated ELISA has a potential utility in a quick, simple and
      reliable acrylamide screening analysis for the medium- and large-sized food
      companies, as well as for residue laboratories and the food industry dealing with
      improving the chemical safety of foods available to the consumer.

PMID- 24725878
TI  - An improved procedure for separation/purification of boron from complex matrices
      and high-precision measurement of boron isotopes by positive thermal ionization
      and multicollector inductively coupled plasma mass spectrometry.
AB  - In order to eliminate boron loss and potential isotopic fractionation during
      chemical pretreatment of natural samples with complex matrices, a three-column
      ion-exchange separation/purification procedure has been modified, which ensures
      more than 98% recovery of boron from each step for a wide range of sample
      matrices, and is applicable for boron isotope analysis by both TIMS and MC-ICP
      MS. The PTIMS-Cs2BO2(+)-static double collection method was developed, ensuring
      simultaneous collection of (133)Cs2(11)B(16)O2(+)(m/z 309) and
      (133)Cs2(10)B(16)O2(+) (m/z 308) ions in adjacent H3-H4 Faraday cups with typical
      zoom optics parameters (Focus Quad: 15 V, Dispersion Quad: -85 V). The external
      reproducibilities of the measured (11)B/(10)B ratios of the NIST 951 boron
      standard solutions of 1000 ng, 100 ng and 10 ng of boron by PTIMS method are +/
      0.060/00, +/-0.160/00 and +/-0.250/00, respectively, which indicates excellent
      precision can be achieved for boron isotope measurement at nanogram level boron
      in natural samples. An on-peak zero blank correction procedure was employed to
      correct the residual boron signals effect in MC-ICP-MS, which gives consistent
      delta(11)B values with a mean of 39.66+/-0.350/00 for seawater in the whole range
      of boron content from 5 ppb to 200 ppb, ensuring accurate boron isotope analysis
      in few ppb boron. With the improved protocol, consistent results between TIMS and
      MC-ICP-MS data were obtained in typical geological materials within a wide span
      of delta(11)B values ranging from -250/00 to +400/00.

PMID- 24725879
TI  - Highly sensitive immunoassay based on SERS using nano-Au immune probes and a nano
      Ag immune substrate.
AB  - A super-high-sensitivity immunoassay based on surface-enhanced Raman scattering
      (SERS) was implemented using the nano-Au immune probes and nano-Ag immune
      substrate. Ultraviolet-visible extinction spectra, transmission electron
      microscopy (TEM) and scanning electron microscopy (SEM) images, and SERS spectra
      were used to characterise the nano-Au immune probes and the nano-Ag immune
      substrate. The nano-Ag immune substrate was prepared by the in situ growth of Ag
      nanoparticles and the subsequent linkage of these nanoparticles with anti
      apolipoprotein B on a silicon wafer. The nano-Ag immune substrate exhibited
      strong SERS activity, excellent reproducibility, and high biospecificity. The
      nano-Au immune probes were prepared by immobilising 4-mercaptobenzoic acid (4MBA)
      molecules as a Raman reporter and anti-apolipoprotein B onto the surfaces of Au
      nanoparticles. It was found that 4MBA induced the aggregation of Au
      nanoparticles, resulting in the generation of vast hot spots. Moreover, the nano
      Au immune probes exhibited strong SERS activity and high biospecificity. A
      sandwich-type immunoassay structure consisting of the nano-Au immune probes and
      nano-Ag immune substrate was used to detect the concentration of apolipoprotein
      B, where the detection limit was as low as 2 fg/mL (3.878*10(-18) mol/L). Taken
      together, the experimental results indicate that the proposed immunoassay
      protocol has a great potential application in biological sensing and clinical
      diagnostics.

PMID- 24725880
TI  - Rapid analysis of persistent organic pollutants by solid phase microextraction in
      serum samples.
AB  - A simple and rapid headspace solid-phase microextraction (HS SPME) based method
      is presented for the determination of Persistent Organic Pollutants (POPs) in
      human serum by gas chromatography (GC) coupled to mass detector (MS) with
      electron impact ionization (EI). As an outcome of the assessment of several
      polymer phases; the one with the best result was the PDMS fiber (100 MUm). A
      multivariate analysis of variance by permutations (PERMANOVA) was performed to
      establish the optimal extraction conditions as a function of temperature and time
      variables. The results were 1 mL serum+200 uL H2SO4 9M+1 mL of deionized water at
      600 rpm with a temperature of 80 degrees C for 50 min to expose the fiber. The
      limits of detection (LOD) for POPs pesticides fell within the 0.22-5.41 ng/mL
      interval, and within 0.07-1.79 ng/mL for PCBs; a linear method was used with
      correlation coefficients (r) higher than 0.99. Recovery percentages at low
      concentrations (15 ng/mL) were 67.8-120.2%, and at high concentrations (75 ng/mL)
      80.2-119.2%. Evaluated precision as percentage Relative Standard Deviation (RSD%)
      of repeatability and reproducibility was within a range of 0.5-9% and 0.3-21%,
      respectively. This analytical method prevents some of the main problems for
      quantifying POPs in human serum, such as the elimination of the solvents, sample
      handling, integration of extraction steps, pre-concentration and introduction of
      samples; consequently, the time and cost of analyzing the sample can be
      significantly reduced. The method developed was applied to determine exposure to
      POPs in samples of children living in different polluted sites in Mexico. In
      children living in indigenous communities results show exposure to DDE (median
      29.2 ng/mL range 17.4-52.2 ng/mL) and HCB (median 2.53 ng/mL range 2.50-2.64
      ng/mL); whereas in the industrial scenario, exposure to HCB (median 2.81 ng/mL
      range 2.61-3.4 ng/mL) and PCBs (median Sigma-PCBs 22.2 ng/ml range 8.2-74.6
      ng/mL) and finally in petrochemical scenario was demonstrated exposure to HCB
      (median 2.81 ng/mL range 2.61-3.4 ng/mL) and PCBs (Sigma-PCBs median 7.9 ng/mL
      range 5.4-114.5 ng/mL).

PMID- 24725882
TI  - Chemometrics tools used in analytical chemistry: an overview.
AB  - This article presents various important tools of chemometrics utilized as data
      evaluation tools generated by various hyphenated analytical techniques including
      their application since its advent to today. The work has been divided into
      various sections, which include various multivariate regression methods and
      multivariate resolution methods. Finally the last section deals with the
      applicability of chemometric tools in analytical chemistry. The main objective of
      this article is to review the chemometric methods used in analytical chemistry
      (qualitative/quantitative), to determine the elution sequence, classify various
      data sets, assess peak purity and estimate the number of chemical components.
      These reviewed methods further can be used for treating n-way data obtained by
      hyphenation of LC with multi-channel detectors. We prefer to provide a detailed
      view of various important methods developed with their algorithm in favor of
      employing and understanding them by researchers not very familiar with
      chemometrics. 

PMID- 24725881
TI  - Stability-indicating capillary zone electrophoresis method for the assessment of
      recombinant human interleukin-11 and its correlation with reversed-phase liquid
      chromatography and biossay.
AB  - A stability-indicating capillary zone electrophoresis (CZE) method was validated
      for the analysis of recombinant human interleukin-11(rhIL-11) using rupatadine
      fumarate, as internal standard (IS). A fused-silica capillary, (50 um i.d.;
      effective length, 40 cm) was used at 25 degrees C; the applied voltage was 20 kV.
      The background electrolyte solution consisted of 50 mmol L(-1) sodium dihydrogen
      phosphate solution at pH 3.0. Injections were performed using a pressure mode at
      50 mbar for 45 s, with detection by photodiode array detector set at 196 nm.
      Specificity and stability-indicating capability were established in degradation
      studies, which also showed that there was no interference of the excipients. The
      method was linear over the concentration range of 1.0-300 ug mL(-1) (r(2)=0.9992)
      and the limit of detection (LOD) and limit of quantitation (LOQ) were 0.2 ug mL(
      1) and 1.0 ug mL(-1), respectively. The accuracy was 100.4% with bias lower than
      1.1%. Moreover, the in vitro cytotoxicity test of the degraded products showed
      significant differences (p<0.05). The method was applied for the content/potency
      assessment of rhIL-11 in biopharmaceutical formulations, and the results were
      correlated to those of a validated reversed-phase LC method (RP-LC) and an TF-1
      cell culture assay, showing non-significant differences (p>0.05). In addition the
      CZE and RP-LC methods were applied for the analysis of rhIL-11 in human plasma.
      Therefore, the proposed alternative method can be applied to monitor stability,
      to assure the batch-to-batch consistency and quality of the bulk and finished
      biotechnology-derived medicine.

PMID- 24725883
TI  - New carbazolo[1,2-a]carbazole derivative as ionophore for anion-selective
      electrodes: remarkable recognition towards dicarboxylate anions.
AB  - A new carbazolo[1,2-a]carbazole derivative was synthesized by expanding the
      binding cavity to explore the possibility of hosting larger anions such as
      dicarboxylate anions. The compound was incorporated as an ionophore into a
      membrane for an anion-selective electrode. The response of the electrode was
      evaluated for oxalate, malonate, succinate, glutarate and adipate in terms of
      calibration characteristics (slope, limit of detection and linear range of the
      response), response time, repeatability, reproducibility and selectivity.
      Nernstian reproducible responses, with very good detection limits, fast responses
      and selectivity not previously observed, were found for all the dicarboxylates
      anions, and the results were especially good in the case of glutarate. In order
      to obtain additional structural information about the complex formed between the
      ionophore and the dicarboxylate anions, (1)H NMR and fluorescence studies were
      carried out. The observed potentiometric selectivity depends on the good
      correspondence between the size of the carbazolocarbazole cavity and the length
      of the dicarboxylate anion, as supported by the NMR and fluorescence studies. 

PMID- 24725884
TI  - Analytical strategies based on multiple headspace extraction for the quantitative
      analysis of aroma components in mushrooms.
AB  - Headspace (HS) and headspace solid phase microextraction (HS-SPME) analysis by
      gas chromatography-mass spectrometry (GC/MS) have been found to be suitable
      methods for the analysis of volatile organic compounds. The objectives of this
      paper are to study the possibilities of multiple headspace extraction (MHE) for
      the quantitative determination of volatile compounds in mushroom samples and to
      compare the results obtained using three different sample treatment techniques.
      For this purpose, HS with two different injection techniques (pressure-loop
      system and gas-tight syringe autosampling system) and HS-SPME have been studied.
      Three processes were optimized for the analysis of 20 volatile compounds by
      experimental design technique based on Central Composite Design (CCD) and Full
      Factorial Design depending on the used methodology. Once the designs were
      finished, a trade off among optimum conditions for each compound analyzed was
      reached. At optimum conditions, appropriate extraction time and sample amount for
      the three techniques used were established. Finally, the methods were validated
      in terms of linearity, detection and quantitation limits and repeatability. The
      most suitable method was then applied to the quantitative analysis of seven
      mushroom samples. A detailed comparison of the analytical performance
      characteristics of HS and HS-SPME as sample treatment techniques for final GC/MS
      determination is given. In addition, MHE has been proved to be an adequate
      technique to avoid matrix effects in complex samples quantitation. Its
      applicability to the determination of volatile mushroom components, along with
      its limitations, is discussed in this work. 

PMID- 24725885
TI  - Loop flow analysis of dissolved reactive phosphorus in aqueous samples.
AB  - The current flow based method for the determination of dissolved reactive
      phosphorus (DRP) suffers interference from salinity (e.g. index refractive
      difference) and the incidentally formed bubbles, which can be a problem for
      optical detection. Here we reported a simple and robust loop flow analysis (LFA)
      method for accurate measurement of DRP in different aqueous samples. The
      chemistry is based on the classic phosphomolybdenum blue (PMB) reaction and the
      PMB formed in a novel cross-shaped flow cell was detected at 700 nm using a
      miniature spectrophotometer. The effects of reagents on the kinetic formation of
      PMB were evaluated. The detection limit was 32 nM with an optical pathlength of
      1cm and the relative standard deviations for repetitive determinations of 1, 2
      and 8 uM phosphate solutions were 1.8% (n=113, without any stoppage during
      repeating analysis for >7h), 1.0% (n=49) and 0.39% (n=9), respectively. The
      analysis time was 4 min sample(-1). The effects of salinity and interfering ions
      (silicate and arsenate) were evaluated and showed no interference under the
      proposed protocol for DRP analysis. Using the LFA method, different aqueous
      samples with a salinity range of 0-34 were analyzed and the results showed
      excellent agreement with the reference method (slope 0.9982+/-0.0063,
      R(2)=0.9987, n=34). Recoveries for spiked samples varied from 95.4% to 103.7%.
      The proposed method showed insignificant interference from salinity, silicate and
      arsenate, higher reproducibility, easier operation and was free of the bubble
      problem.

PMID- 24725886
TI  - Frits coated with nano-structured conducting copolymer for solid-phase extraction
      of polycyclic aromatic hydrocarbons in water samples and liquid chromatographic
      analysis.
AB  - A novel nano-structured conducting copolymer of pyrrole and o-toluidine was
      electrosynthesized on steel frit as a new sorbent. The applicability of the frit
      was assessed for the solid-phase extraction (SPE) of Polycyclic aromatic
      hydrocarbons (PAHs) by coupling with HPLC-UV. The combination of pyrrole and o
      toluidine in a copolymer form presents desirable opportunities to produce
      materials for new applications. The scanning electron microscopy (SEM), energy
      dispersive X-ray spectroscopy (EDX) and FTIR spectrum for the coated frit were
      studied. Improved lifetime and satisfactory extraction efficiency were obtained
      by doping with dodecylbenzenesulfonate (DBS) and oxalate groups into the
      framework of copolymer. The effects of potential, time and solution concentration
      (pyrrole, o-toluidine, DBS and oxalic acid) were evaluated in the coating step.
      The effects of various parameters on the efficiency of the solid-phase extraction
      process, such as the sample loading rate, elution solvent type, salt effect,
      volume and flow rate of sample and elution solvent, were investigated. Under
      optimum conditions, LODs were 0.01-0.08 ng mL(-1). The method showed linearity in
      the range of 0.1-300 ng mL(-1) with coefficients of determination >0.98. The
      intra-day (n=7) RSDs obtained at an 8 ng mL(-1) concentration level were <11.4%
      under optimized conditions respectively. The recoveries (8 and 40 ng mL(-1))
      ranged from 64% to 119%.

PMID- 24725887
TI  - Solid-phase extraction approach for phospholipids profiling by titania-coated
      silica microspheres prior to reversed-phase liquid chromatography-evaporative
      light scattering detection and tandem mass spectrometry analysis.
AB  - A novel strategy for selectively adsorbing phospholipids (PLs) on titania-coated
      silica core-shell microspheres (TiO2/SiO2) was developed. The TiO2/SiO2
      microspheres were prepared through water-vapor-induced internal hydrolysis and
      then characterized by SEM, UV-vis spectroscopy, X-ray diffraction, and
      measurements of Brunauer-Emmett-Teller surface area. Analyses showed that the
      titania layer was uniformly distributed onto the surface of silica particles. The
      TiO2/SiO2 microspheres were employed as sorbent in solid-phase extraction (SPE),
      and their absorptive ability was investigated by reversed-phase liquid
      chromatography-evaporative light scattering detection (RPLC-ELSD). Important
      factors that affect the extraction, such as loading buffer, eluting buffer, and
      elution volume, were investigated in detail and optimized by using standard
      samples. Results reveal that the developed SPE approach had higher recoveries for
      PLs than that based on pure TiO2 particles. The proposed SPE method was used for
      extraction of PLs from serum and showed great potential for identifying more
      kinds of endogenous PL metabolites by ultra performance liquid chromatography
      with quadrupole time-of-flight mass spectrometry (UPLC-QTOF MS). The proposed SPE
      method with the composite sorbent was used to screen PLs from a biological matrix
      with high selectivity and efficiency. This approach is a promising method for
      selective extraction of PLs in lipidomics or phospholipidomics. 

PMID- 24725888
TI  - Direct analysis of airborne mite allergen (Der f1) in the residential atmosphere
      by chemifluorescent immunoassay using bioaerosol sampler.
AB  - Dermatophagoides farinae allergen (Der f1) is one of the most important indoor
      allergens associated with allergic diseases in humans. Mite allergen Der f1 is
      usually associated with particles of high molecular weight; thus, Der f1 is
      generally present in settled dust. However, a small quantity of Der f1 can be
      aerosolized and become an airborne component. Until now, a reliable method of
      detecting airborne Der f1 has not been developed. The aim of this study was to
      develop a fiber-optic chemifluorescent immunoassay for the detection of airborne
      Der f1. In this method, the Der f1 concentration measured on the basis of the
      intensity of fluorescence amplified by an enzymatic reaction between the labeled
      enzyme by a detection antibody and a fluorescent substrate. The measured Der f1
      concentration was in the range from 0.49 to 250 ng/ml and a similar range was
      found by enzyme-linked immunosorbent assay (ELISA). This method was proved to be
      highly sensitive to Der f1 compared with other airborne allergens. For the
      implementation of airborne allergen measurement in a residential environment, a
      bioaerosol sampler was constructed. The airborne allergen generated by a
      nebulizer was conveyed to a newly sampler we developed for collecting airborne
      Der f1. The sampler was composed of polymethyl methacrylate (PMMA) cells for
      gas/liquid phases and some porous membranes which were sandwiched in between the
      two phases. Der f1 in air was collected by the sampler and measured using the
      fiber-optic immunoassay system. The concentration of Der f1 in aerosolized
      standards was in the range from 0.125 to 2.0 mg/m(3) and the collection rate of
      the device was approximately 0.2%.

PMID- 24725890
TI  - An easy way to make a good anti-tumor chimeric antigen receptor T cell?

PMID- 24725889
TI  - Microglial activation mediates host neuronal survival induced by neural stem
      cells.
AB  - The rational of neural stem cells (NSCs) in the therapy of neurological disease
      is either to replace dead neurons or to improve host neuronal survival, the
      latter of which has got less attention and the underlying mechanism is as yet
      little known. Using a transwell co-culture system, we reported that, in
      organotypic brain slice cultures, NSCs significantly improved host neuronal
      viability. Interestingly, this beneficial effect of NSCs was abrogated by a
      microglial inhibitor minocycline, while it was mimicked by a microglial agonist,
      Toll-like receptor 9 (TLR9) ligand CpG-ODN, which supports the pro-vital
      mediation by microglia on this NSCs-improved neuronal survival. Moreover, we
      showed that NSCs significantly induced host microglial movement and higher
      expression of a microglial marker IBA-1, the latter of which was positively
      correlated with TLR9 or extracellular-regulated protein kinases 1/2 (ERK1/2)
      activation. Real-time PCR revealed that NSCs inhibited the expression of pro
      inflammatory molecules, but significantly increased the expression of molecules
      associated with a neuroprotective phenotype such as CX3CR1, triggering receptor
      expressed on myeloid cells-2 (TREM2) and insulin growth factor 1 (IGF-1).
      Similarly, in the microglia cells, NSCs induced the same microglial response as
      that in the slices. Further treatment with TLR9 ligand CpG-ODN, TLR9 inhibitor
      chloroquine (CQ) or ERK1/2 inhibitor U0126 demonstrated that TLR9-ERK1/2 pathway
      was involved in the NSCs-induced microglial activation. Collectively, this study
      indicated that NSCs improve host neuronal survival by switching microglia from a
      detrimental to a neuroprotective phenotype in adult mouse brain, and the
      microglial TLR9-ERK1/2 pathway seems to participate in this NSCs-mediated rescue
      action. 

PMID- 24725892
TI  - Long-term successful arthroscopic repair of large and massive rotator cuff tears
      with a functional and degradable reinforcement device.
AB  - BACKGROUND: Rotator cuff repair is a procedure with varying outcomes, and there
      has been subsequent interest in devices that reinforce the repair and enhance
      structural and functional outcomes. The objective of this study was to determine
      these outcomes for arthroscopic repair of large and massive rotator cuff tears
      augmented with a synthetic absorbable mesh designed specifically for
      reinforcement of tendon repair by imaging and clinical assessments. MATERIALS AND
      METHODS: Consecutive arthroscopic repairs were performed on 18 patients with
      large to massive rotator cuff tears by use of a poly-l-lactic acid synthetic
      patch as a reinforcement device and fixation with 4 sutures. Patients were
      assessed preoperatively and at 6 months, 12 months, and a mean of 42 months after
      surgery by the American Shoulder and Elbow Surgeons (ASES) shoulder score to
      evaluate clinical performance and at 12 months by ultrasound to assess structural
      repair. RESULTS: Ultrasound showed that 15 of 18 patients had intact rotator cuff
      repair at 12 months; at 42 months, an additional patient had a failed repair.
      Patients showed improvement in the ASES shoulder score from 25 preoperatively to
      71 at 12 months and 70 at 42 months after surgery. Patients with intact rotator
      cuff (n = 14) at 42 months had an ASES shoulder score of 82. DISCUSSION: The poly
      l-lactic acid bioabsorbable patch designed specifically to reinforce the surgical
      repair of tendons supported successful repair of large to massive rotator cuff
      tears in 83% of patients at 12 months after surgery and 78% of patients at 42
      months after surgery, with substantial functional improvement.

PMID- 24725893
TI  - Reverse total shoulder arthroplasty for the treatment of proximal humeral
      fractures: patterns of use among newly trained orthopedic surgeons.
AB  - BACKGROUND: This study compared the use of reverse and hemishoulder arthroplasty
      for the treatment of proximal humeral fractures among orthopedic surgeons taking
      part II of the American Board of Orthopaedic Surgery board examination. We
      hypothesized that the use of reverse shoulder arthroplasty for fractures in the
      elderly is increasing amongst newly trained orthopedic surgeons. MATERIALS AND
      METHODS: We queried the American Board of Orthopaedic Surgery database for the
      cases of proximal humeral fractures treated with arthroplasty submitted between
      2005 and 2012. We evaluated the prosthesis used, patient-specific factors,
      complications, and the difference in use by shoulder fellowship-trained surgeons.
      RESULTS: From 2005 to 2012, 5395 board-eligible orthopedic surgeons submitted
      cases to the database. Of these, 435 (mean, 54 per year) were proximal humeral
      fractures treated with arthroplasty. The overall incidence of reverse shoulder
      arthroplasty for fracture increased from 2% to 4% during 2005 to 2007 to 38% in
      2012. Shoulder surgeons treated 5 times more proximal humeral fractures with
      shoulder arthroplasty and were also more than 20 times more likely to use a
      reverse implant (P < .0001). The difference in complication rates between reverse
      and hemishoulder arthroplasty was not significant (P = .49). Patients who
      received a hemiarthroplasty tended to be younger (mean age, 70.8 vs 75.7 years; P
      = .0015). CONCLUSIONS: Overall, the use of a hemiarthroplasty for fracture is
      still more common (62% in 2012), although the relative proportion of reverse
      implants is rising. Among shoulder surgeons, more than 50% of the arthroplasties
      performed for fractures during the past 3 years (2010-2012) have been reverse
      arthroplasties.

PMID- 24725891
TI  - Physicochemical characteristics of nanomaterials that affect pulmonary
      inflammation.
AB  - The increasing manufacture and use of products based on nanotechnology raises
      concerns for both workers and consumers. Various studies report induction of
      pulmonary inflammation after inhalation exposure to nanoparticles, which can vary
      in aspects such as size, shape, charge, crystallinity, chemical composition, and
      dissolution rate. Each of these aspects can affect their toxicity, although it is
      largely unknown to what extent. The aim of the current review is to analyse
      published data on inhalation of nanoparticles to identify and evaluate the
      contribution of their physicochemical characteristics to the onset and
      development of pulmonary inflammation. Many physicochemical characteristics of
      nanoparticles affect their lung deposition, clearance, and pulmonary response
      that, in combination, ultimately determine whether pulmonary inflammation will
      occur and to what extent. Lung deposition is mainly determined by the physical
      properties of the aerosol (size, density, shape, hygroscopicity) in relation to
      airflow and the anatomy of the respiratory system, whereas clearance and
      translocation of nanoparticles are mainly determined by their geometry and
      surface characteristics. Besides size and chemical composition, other
      physicochemical characteristics influence the induction of pulmonary inflammation
      after inhalation. As some nanoparticles dissolve, they can release toxic ions
      that can damage the lung tissue, making dissolution rate an important
      characteristic that affects lung inflammation. Fibre-shaped materials are more
      toxic to the lungs compared to spherical shaped nanoparticles of the same
      chemical composition. In general, cationic nanoparticles are more cytotoxic than
      neutral or anionic nanoparticles. Finally, surface reactivity correlates well
      with observed pulmonary inflammation. With all these characteristics affecting
      different stages of the events leading to pulmonary inflammation, no unifying
      dose metric could be identified to describe pulmonary inflammation for all
      nanomaterials, although surface reactivity might be a useful measure. To
      determine the extent to which the various characteristics influence the induction
      of pulmonary inflammation, the effect of these characteristics on lung
      deposition, clearance, and pulmonary response should be systematically evaluated.
      The results can then be used to facilitate risk assessment by categorizing
      nanoparticles according to their characteristics. 

PMID- 24725894
TI  - Intermediate and long-term follow-up of total shoulder arthroplasty for the
      management of postcapsulorrhaphy arthropathy.
AB  - BACKGROUND: The purpose of this study was to evaluate the subjective and
      objective outcomes in patients undergoing total shoulder arthroplasty for
      treatment of postcapsulorrhaphy arthropathy (CA) and compare them with outcomes
      in patients undergoing total shoulder arthroplasty for primary glenohumeral
      osteoarthritis (OA). METHODS: Total shoulder arthroplasty was used to treat 25
      consecutive CA patients (25 shoulders) at our institution; of these, 22 patients
      were available for follow-up. An age-matched cohort of 19 consecutive patients
      (20 shoulders) who were treated with total shoulder arthroplasty for primary
      glenohumeral OA was compared with the CA group. Patients were evaluated by
      physical examination and patient outcome measures (American Shoulder and Elbow
      Surgeons assessment and Simple Shoulder Test). Complications, reoperations, and
      subscapularis function was also recorded. RESULTS: Compared with the CA group,
      the OA group achieved greater forward elevation (165 degrees  vs 147 degrees ; P
      = .036) and greater external rotation (56 degrees  vs. 45 degrees ; P = .04);
      however, no significant differences were seen in subjective patient scores
      between the 2 groups for Simple Shoulder Test (P = .90), American Shoulder and
      Elbow Surgeons assessment (P = .65), and pain scores (P = .80). The difference in
      the number of revision surgeries in the OA group compared with the CA group (1 vs
      4) was not significant (P = .35). A significantly higher number of patients in
      the CA group had subscapularis insufficiency compared with the OA group (5 CA vs
      0 OA; P = .049). CONCLUSIONS: Our findings suggest that when compared with
      patients undergoing total shoulder arthroplasty for primary OA, CA patients
      experience similar outcomes with respect to revision surgery, pain relief, and
      subjective self-assessment and have a higher incidence of subscapularis
      insufficiency.

PMID- 24725895
TI  - Factors that predict postoperative motion in patients treated with reverse
      shoulder arthroplasty.
AB  - BACKGROUND: Reverse shoulder arthroplasty (RSA) has proven to be a useful yet
      inconsistent tool to manage a variety of pathologic conditions. Factors believed
      to lead to poor postoperative range of motion (ROM) may be associated with
      preoperative diagnosis, poor preoperative ROM, and surgical factors such as
      inability to lengthen the arm. The purpose of this study was to analyze multiple
      factors that may be predictive of motion after RSA. Our hypothesis is that
      intraoperative ROM is most predictive of postoperative ROM. METHODS: Between
      February 2003 and April 2011, 540 patients (217 men and 323 women) treated with
      RSA were evaluated with measurements of preoperative, intraoperative, and
      postoperative ROM at a follow-up, where ROM was found to have plateaued at 1 year
      as determined by a pilot study. A regression analysis was performed to define
      independent predictive factors of postoperative active ROM. RESULTS:
      Intraoperative forward flexion was the strongest predictor of final postoperative
      ROM, followed by gender and preoperative ROM. Age and arm lengthening were not
      significant independent predictors. Controlling for gender and preoperative ROM,
      patients with an intraoperative elevation of 90 degrees  gained 29 degrees  in
      postoperative forward elevation (P < .001), 120 degrees  gained approximately 40
      degrees  in postoperative forward elevation (P < .001), 150 degrees  gained
      approximately 56 degrees  in postoperative forward elevation (P < .001) and 180
      degrees  gained approximately 62 degrees  in postoperative forward flexion (P <
      .001). CONCLUSIONS: Intraoperative forward flexion is the strongest predictor of
      postoperative ROM. Surgeons may use intraoperative motion as a powerful decision
      making tool regarding soft tissue tension in RSA.

PMID- 24725896
TI  - Morbid obesity in total shoulder arthroplasty: risk, outcomes, and cost analysis.
AB  - BACKGROUND: A rate of obesity in the US population and the rate of total shoulder
      arthroplasty (TSA) has increased over the past decade. Little information exists
      concerning the number of morbidly obese patients undergoing TSA or how these
      patients compare with their non-obese counterparts. The goal of this study was to
      determine whether morbidly obese patients exhibit greater rates of postoperative
      in-hospital complications, mortality, or utilization of resources. METHODS: We
      used the Nationwide Inpatient Sample to analyze 31,924 patients undergoing TSA
      between 1998 and 2008. Multivariate analysis with logistic regression modeling
      was used to compare patients based on body mass index for various outcomes.
      RESULTS: Among morbidly obese patients, predictors of death included age (odds
      ratio, 1.06; 95% confidence interval, 1.01-1.11) and Deyo score. A comparison of
      hospital costs among patients showed that increased patient body mass index led
      to increased hospital charges independent of physician charges ($38,103.88 in
      morbidly obese patients vs $33,521.66 in non-obese patients, P = .0001). An
      increased length of stay was observed in morbidly obese patients (2.84 days vs
      2.52 days in obese patients and 2.56 days in non-obese patients, P = .003).
      Respiratory dysfunction occurred more commonly in morbidly obese patients than in
      non-obese patients (1.2% vs 0.7%; odds ratio, 1.61; P < .01). CONCLUSIONS: Obese
      patients tend to have longer hospital stays, an increased risk of postoperative
      respiratory complications, and higher costs. Although there was a trend toward an
      increased early postoperative mortality rate, obesity was not associated with an
      increased incidence of most complications. These findings should be supplemented
      with further research to assist patient counseling and risk adjustment for obese
      patients undergoing TSA.

PMID- 24725897
TI  - The incidence of proximal humeral fractures in New York State from 1990 through
      2010 with an emphasis on operative management in patients aged 65 years or older.
AB  - BACKGROUND: Proximal humeral fractures are commonly encountered injuries. The
      development of locking plate technology and reverse shoulder arthroplasty may
      have changed the treatment patterns of these fractures. METHODS: We used the
      Statewide Planning and Research Cooperative System database in New York State to
      determine the incidence of proximal humeral fractures from 1990 through 2010 and
      the choice of treatment: closed reduction-internal fixation, open reduction
      internal fixation (ORIF), hemiarthroplasty (HA), or total shoulder arthroplasty
      (TSA). RESULTS: The population-adjusted incidence per 100,000 increased from
      15.35 in 1990 to 19.4 in 2010 (P < .0001). In patients aged 65 years or older,
      the incidence increased from 78.9 in 1990 to 101.0 in 2010 (P < .0001). In 1990,
      20.4% of proximal humeral fractures were treated operatively; in 2010, this
      increased to 28.6% (P < .0001). Closed reduction-internal fixation/ORIF accounted
      for 58.4% of operative cases in 1990, decreasing to 46.6% in 2001 and increasing
      to 59.4% in 2010. HA was used in 27.1% of operative cases in 1990, increasing to
      41% in 2001 and decreasing to 29.4% in 2010. TSA was used in 6.4% of operative
      cases in 1990, decreasing to 1.5% in 2001 with an increase to 7.5% in 2010.
      DISCUSSION: The incidence of proximal humeral fractures in patients aged 65 or
      older increased by 28% between 1990 and 2010, and operative management increased
      by more than 40%. The use of ORIF increased between 2001 and 2010, corresponding
      with the use of locking plate technology. There was an associated decrease in HA.
      TSA increased between 2006 and 2010, corresponding to the use of reverse shoulder
      arthroplasty.

PMID- 24725898
TI  - Immobilization in external rotation combined with abduction reduces the risk of
      recurrence after primary anterior shoulder dislocation.
AB  - BACKGROUND: We aimed to compare the effectiveness of immobilization in abduction
      and external rotation vs immobilization in adduction and internal rotation after
      primary anterior dislocation of the shoulder. METHODS: The study randomized 102
      patients (age range, 15-55 years) with the diagnosis of primary anterior
      dislocation of the shoulder to receive immobilization in adduction and internal
      rotation (AdIR, n = 51) using sling and swathe bandage or immobilization in
      abduction and external rotation (AbER, n = 51) with a stabilizer brace. Patients
      received a rehabilitation program 3 weeks after the intervention. RESULTS: After
      a 24-month follow-up, 33.3% in the AdIR group and 3.9% in the AbER group had
      recurrence (P < .001). The difference in the recurrence rate was greater in the
      subgroup aged between 31 and 40 years (44.8% in the AdIR group and 3.8% in the
      AbER group, P < .001). Ten patients in the AbER group (19.6%) and 3 in the AdIR
      group (5.8%) discontinued shoulder immobilization before 3 weeks (P = .03). In
      patients without recurrence, the anterior apprehension test was positive in 6 of
      34 in the AdIR group (17.6%) and in 4 of 49 in the AbER group (8.1%, P = .19).
      CONCLUSIONS: Immobilization with the shoulder joint in abduction and external
      rotation is an effective method to reduce the risk of recurrence after primary
      anterior shoulder dislocations and should be preferred to the traditional method
      of immobilization in adduction and internal rotation in clinical practice.

PMID- 24725899
TI  - Successful injection of the acromioclavicular joint with use of ultrasound:
      anatomy, technique, and follow-up.
AB  - BACKGROUND: Injection into the acromioclavicular (AC) joint is often inaccurate
      (approximately 50%) even in experienced hands. In light of new anatomic
      observations, we evaluate accuracy of an innovative ultrasound-guided method and
      follow the clinical course of successful therapeutic injections. METHOD: Relevant
      anatomy was investigated in 200 three-dimensional computed tomography scans, 100
      magnetic resonance images, and 14 cadavers. Baseline measurements of joint depth
      and width were performed ultrasonically in 100 normal volunteers; 50 symptomatic
      patients were injected. Uniquely in a clinical ultrasound study, injection
      success was documented by arthrography. Outcomes after concomitant steroid
      instillation were observed for 6 months by visual analog scale (VAS) scores and
      pain provocation test results. RESULTS: Anatomic studies showed that the widest
      area for joint penetration was anterior superior. Injection success rate was 96%,
      overwhelmingly on the first needle pass. Shallow joint depth allowed access with
      a standard 3-cm needle. Joint width diminished with age but did not reduce
      injection success. Cadaveric joints admitted 1.2 +/- 0.5 mL, but fluid ingress
      was initially blocked by soft tissues in one third of both cadaveric and clinical
      cases. Diligent follow-up after steroid injection showed sustained pain relief in
      the majority with isolated AC disease but significantly less in those with
      concomitant shoulder disorders. CONCLUSION: This high level of clinical injection
      success, irrefutably substantiated with arthrography, has not been previously
      demonstrated. The anterior superior aspect of the joint is the preferred place
      for entry. Initial intra-articular blockage to fluid inflow is common but can be
      surmounted. Encouraging 6-month results of steroid instillation in isolated AC
      disease do not apply to patients with coexisting shoulder pathologic processes.

PMID- 24725900
TI  - Specific patient-related prognostic factors for rotator cuff repair: a systematic
      review.
AB  - BACKGROUND: Many studies that describe factors affecting outcome in primary
      rotator cuff repair (RCR) have been published, but so far there is no review that
      summarizes them. This systematic review was conducted to identify prognostic
      factors influencing functional (clinical) outcome and radiologically proven cuff
      integrity after RCR. METHODS: A literature search was conducted up to July 2013
      for prospective studies that describe prognostic factors affecting outcome in
      primary RCR. Inclusion criteria were open or arthroscopic repair of a full
      thickness supraspinatus or infraspinatus tear. Included outcome measures were
      shoulder function and cuff integrity. Studies describing revision surgery, muscle
      transpositions, and subscapular or partial-thickness tears and those with
      retrospectively collected data were excluded, as were studies without linear or
      multivariate regression. The literature search resulted in 662 hits, and 12 of
      those studies were included in this review. RESULTS: Moderate evidence was found
      for increasing age, larger tear size, and additional biceps or acromioclavicular
      procedures to have a negative influence on cuff integrity at follow-up as well as
      for Workers' Compensation Board status to have a negative influence on functional
      outcome after RCR. There is limited evidence that performance of an additional
      acromioclavicular procedure has a negative influence on functional outcome. There
      was insufficient evidence for other described prognostic factors. CONCLUSION:
      Several patient-specific factors influencing functional and radiologic outcome
      after RCR have been identified. These factors can guide orthopedic surgeons in
      their decision-making process as to whether to operate on their patients.

PMID- 24725901
TI  - The histologic and biomechanical response of two commercially available small
      glenoid anchors for use in labral repairs.
AB  - BACKGROUND: This study examined histologic characteristics and biomechanical
      performance of 2 commercially available, small glenoid anchors. METHODS: Adult
      research dogs (n = 6) were used for histologic analysis. Anchors were inserted
      into the lateral rim of the glenoid using the manufacturer's protocol. The dogs
      were humanely euthanatized 8 weeks after anchor implantation, and the glenoids
      were collected for histologic analysis. Bone socket width data were compared for
      statistically significant (P < .05) differences. In addition, 4 matched pairs (n
      = 8) of human cadaveric glenoids were instrumented with 1 BioComposite SutureTak
      (Arthrex, Naples, FL, USA) and 1 JuggerKnot (Biomet, Warsaw, IN, USA) suture
      anchor in the anterior-inferior quadrant. Anchor constructs were preloaded to 5
      N, cycled from 5 to 25 N for 100 cycles, and then pulled to failure. RESULTS: All
      JuggerKnot anchor sites were cyst-like cavities with a rim of dense lamellar
      bone. All BioComposite SutureTak anchor sites contained intact anchors with close
      approximation of anastomosing trabeculae of lamellar bone. At 8 weeks after
      implantation, mean socket width of the JuggerKnot anchor sites was 6.3 +/- 2.5
      mm, which was significantly (P = .013) larger than the mean socket width of 2.7
      +/- 0.7 mm measured for the BioComposite SutureTak anchor sites. The JuggerKnot
      anchor demonstrated larger displacements during subfailure cyclic loading (2.9 +/
      1.0 mm compared with 1.3 +/- 0.4 mm) and load to failure tests (13.7 +/- 6.6 mm
      compared with 3.2 +/- 0.5 mm). Statistical differences (P < .01) existed in every
      category except ultimate load. CONCLUSIONS: Based on the biomechanical in human
      bone and histologic findings in canine subjects, the all-suture anchor may be at
      risk for clinical failure.

PMID- 24725902
TI  - Poor utility of serum interleukin-6 levels to predict indolent periprosthetic
      shoulder infections.
AB  - BACKGROUND: Infection after shoulder arthroplasty can present a diagnostic
      challenge. The purpose of this study was to evaluate the utility of serum
      interleukin-6 (IL-6) levels in diagnosis of periprosthetic infection in patients
      undergoing revision shoulder arthroplasty. METHODS: We prospectively enrolled 69
      patients who underwent revision shoulder arthroplasty at one institution. All
      patients underwent a standard preoperative and intraoperative workup for
      infection, which included shoulder aspirate culture, erythrocyte sedimentation
      rate, C-reactive protein level, tissue culture, and frozen section analysis. In
      addition, serum levels of IL-6 were measured preoperatively in all patients.
      Infection classification was divided into 4 groups, (1) definite, (2) probable,
      (3) possible, and (4) no infection, on the basis of previously reported criteria
      using intraoperative cultures and preoperative and intraoperative findings of
      infections. RESULTS: Of the 69 patients, 24 were classified as having a definite
      or probable infection. Propionibacterium acnes was the offending organism for the
      majority of these cases (20 of 24, 83%). IL-6 was not a sensitive marker of
      infection for these patients (sensitivity: 3 of 24, 12%; specificity: 3 of 45,
      93%). The sensitivity of serum IL-6 was lower compared with erythrocyte
      sedimentation rate (sensitivity: 10 of 24, 42%; specificity: 37 of 45, 82%) and C
      reactive protein level (sensitivity: 11 of 24, 46%; specificity: 42 of 45, 93%).
      For the non-P. acnes cases (1 Staphylococcus aureus, 1 Enterobacter cloacae, 2
      coagulase-negative Staphylococcus species), the sensitivity of IL-6 was 25% (1 of
      4). CONCLUSION: Serum IL-6 is not an effective marker for diagnosis of infection
      in shoulder arthroplasty. On the basis of this large prospective study, we do not
      recommend its use as a preoperative diagnostic test in patients undergoing
      revision shoulder arthroplasty.

PMID- 24725903
TI  - Complex shoulder arthroplasty in patients with skeletal dysplasia can decrease
      pain and improve function.
AB  - BACKGROUND: Patients with skeletal dysplasia are prone to the development of
      degenerative shoulder disease requiring shoulder arthroplasty at a younger age
      than in the general population. To date there have been no published reports on
      the complexities or outcome of shoulder arthroplasty in this unique patient
      group. METHODS: This is a review of 13 shoulder arthroplasties in 10 patients
      with skeletal dysplasia with mean follow-up of 7 years (2-17.6 years). There were
      4 men and 6 women with a mean age of 53.1 years (23-76 years), mean height of 148
      cm (122-177 cm), and mean weight of 60 kg (27-80 kg). RESULTS: The mean Oxford
      Shoulder Score increased from 13 (5-20) preoperatively to 28 (18-38) at final
      follow-up. Patients improved significantly in 2 of 8 Short Form 36 health-related
      quality of life domains: physical function (P = .04) and bodily pain (P = .04).
      Function was better in those who underwent nonconstrained total shoulder
      arthroplasty as opposed to hemiarthroplasty. Four (31%) required reoperation: 1
      excision of heterotopic ossification, 1 relocation for anterior instability, and
      2 revisions for periprosthetic fracture and glenoid erosion. CONCLUSION: Shoulder
      arthroplasty is effective at relieving pain, optimizing movement, and improving
      function for patients with skeletal dysplasia; however, compared with the general
      population, there is a higher complication rate and function is not as good.
      Furthermore, this procedure is less effective at restoring health-related quality
      of life than total hip arthroplasty or total shoulder arthroplasty performed for
      osteoarthritis in the general population. Custom implants may be required to
      compensate for short stature and rotator cuff and glenoid deficiency.

PMID- 24725905
TI  - Osteoradionecrosis--a review of current concepts in defining the extent of the
      disease and a new classification proposal.
AB  - Osteoradionecrosis (ORN) is potentially a debilitating and serious consequence of
      radiotherapy to the head and neck. Although it is often defined as an area of
      exposed bone that does not heal, it can also exist without breaching the mucosa
      or the skin. Currently, 3 classifications of ORN are in use, but they depend on
      the use of hyperbaric oxygen or are too complicated to be used as a simple aide
      memoire, and include features that do not necessarily influence its clinical
      management. We propose a new classification to cover these shortcomings and to
      take into account the increasingly widespread use of antifibrotic medical
      treatment. We classified a series of 85 patients with varying severities of ORN
      into 4 groups. An analysis of the outcomes of the series showed that the
      classification staged the severity of the condition simply and that the stage was
      relevant to both treatment and outcome. The new classification was therefore
      verified by the series presented. 

PMID- 24725904
TI  - Health-related quality of life in epilepsy patients receiving anti-epileptic
      drugs at National Referral Hospitals in Uganda: a cross-sectional study.
AB  - BACKGROUND: Epilepsy is a devastating disorder that impacts on patients' quality
      of life, irrespective of use of anti epileptic drugs (AEDs). This study estimates
      the health-related quality of life (HRQOL) and its associated predictors among
      epilepsy patients receiving AEDs. METHODS: A total of 175 epilepsy patients
      already receiving AED for at least 3 months were randomly selected and
      interviewed from mental clinics at Mulago and Butabika national referral
      hospitals in Uganda between May - July 2011. A HRQOL index, the primary outcome,
      was constructed using items from Quality Of Life in Epilepsy Inventory (QOLIE-31)
      and the Hospital Anxiety and Depression Scale (HADS) questionnaires. The internal
      consistency and adequacy of these items was also computed using Cronbach's alpha
      and Kaiser-Meyer-Olkin tests. Partial correlations were used to evaluate the
      contribution of the health dimensions (mental, psychological, social, physical
      functioning and emotional well being) and, multiple linear regressions to
      determine factors independently associated with HRQOL. RESULTS: Just about half
      of the respondents (54%) were males, and nearly two thirds (62%) had received
      AEDs for at least 12 months. The average age was 26.6 years (SD = 11.1). The
      overall HRQOL mean score was 58 (SD = 13) on a scale of 0-100. The average scores
      of different dimensions or subscales ranged from 41 (physical) to 65
      (psychological). At least three quarters (75%) of all subscales had good internal
      consistency and adequacy. The largest variations in the overall HRQOL were
      explained by social and mental functioning; each accounting for about 30% of the
      difference in the HRQOL but seizure control features explained a little (6%)
      variation. Factors negatively associated with HRQOL were poly-therapy (-1.16, p =
      0.01) and frequency of seizures (-2.29, p = 0.00). Other factors associated with
      overall HRQOL included drug side effects, sex, marital status and education.
      Duration on AEDs was not a significant predictor of HRQOL. CONCLUSION: The HRQOL
      for epilepsy patients on AEDs is very low. The predictors of low HRQOL were socio
      factors (marital status, education) and drug side effects, frequency of seizure,
      and type of therapy.

PMID- 24725906
TI  - Prognosis value of early diffusion MRI in Legg Perthes Calve disease.
AB  - PURPOSE: To evaluate diffusion MRI of the proximal femoral epiphysis and
      metaphysis as a prognosis factor in Legg Calve Perthes (LCP) disease. METHODS:
      Thirty-one children (mean age 5.5 years, range 2.5-10.5) with unilateral LCP were
      included in a prospective, consecutive series. Radiographs were analysed and
      classified as per Herring criteriae. Mean follow-up was 19 months (range 6-30).
      Forty-nine MRI scans were performed at either the condensation or fragmentation
      stage. Apparent Diffusion Coefficient (ADC) of both the femoral epiphysis and
      metaphysis were measured bilaterally and ADC ratio were calculated, then compared
      to the Herring group. RESULTS: Sixteen hips were rated Herring A or B, 3 Herring
      B-C and 12 Herring C. ADC was increased in affected hips compared to unaffected
      sides, both at the femoral epiphysis (P<0.001) and metaphysis (P<0.0001). ADC
      ratio of the femoral metaphysis was positively correlated to Herring
      classification: if superior to 1.63, it was associated with a bad prognosis
      (Herring B-C or C) (P=0.0017, sensitivity=89%, specificity=58%). Interobserver
      reliability of ADC measurement was excellent. The 1.63 threshold could be
      determined as early as the condensation stage. CONCLUSIONS: Diffusion presents
      several advantages including being non radiating and non invasive. It does not
      need contrast medium administration and it can be performed without anaesthesia.
      The origin of the increased ADC remains unknown. Basically, it reflects molecular
      changes (true diffusion) but it is also influenced by the vascular supply (pseudo
      diffusion). ADC ratio could provide an early prognosis before Herring
      classification is applicable. LEVEL OF EVIDENCE: Level III. Prospective
      uncontrolled study.

PMID- 24725907
TI  - Atlanto-axial dislocation complicating a type II odontoid fracture. Reduction and
      final fixation.
AB  - A case of traumatic posterolateral C1-C2 dislocation associated with odontoid
      fracture is reported. This is a rare case of traumatic posterolateral C1-C2
      dislocation associated with odontoid fracture. Its management is discussed. A
      traumatic dislocation of atlanto-axial joint associated with an odontoid fracture
      remains a rare injury. No case of posterior dislocation has been reported so far
      in the literature with this type of management. The case is of a 25 year-old-man
      with a primary atlanto-axial posterolateral dislocation associated with a type II
      displaced odontoid fracture without any neurological complication. The patient
      underwent gentle traction during 24 hours with a halo frame. An incomplete
      reduction was achieved. Two days later, a complete reduction was obtained thanks
      to a preoperative manual traction maintained by a Mayfield (R) modified skull
      clamp. Anterior C1-C2 fixation was performed according to Vaccaro's technique.
      The patient wore a cervical collar and underwent physiotherapy during three
      months. To our best knowledge, this case represents the first traumatic atlanto
      axial dislocation associated with an odontoid fracture which was treated through
      retropaharyngeal approach. This had been rendered possible thanks to the final
      reduction maneuver in extension.

PMID- 24725908
TI  - Discussion.

PMID- 24725909
TI  - Outcomes of covered versus bare-metal balloon-expandable stents for aortoiliac
      occlusive disease.
AB  - OBJECTIVE: Randomized trials and retrospective data suggest that covered balloon
      expandable (CBE) stents have better short-term patency compared with balloon
      expandable bare-metal stents (BMSs) in the treatment of iliac artery disease.
      This study evaluated midterm outcomes of BMSs vs CBE stents placed in the common
      iliac artery (CIA) for aortoiliac occlusive disease. METHODS: All endovascular
      interventions for symptomatic peripheral arterial occlusive disease performed at
      a single institution from 2006 to 2012 were reviewed. Patients undergoing stent
      placement in the CIA segment were included in the analysis. Demographic data,
      TransAtlantic Inter-Society Consensus (TASC) classification, stent type, patency,
      and limb reinterventions were compared. RESULTS: For treatment of de novo distal
      aorta or CIA stenosis, 254 procedures were performed in 162 patients. BMSs were
      used in 190 arteries; CBE stents were used in 64 arteries. There was no
      difference in age, gender, or TASC classification between the two groups. Mean
      follow-up was 22 +/- 16 months. Primary patency, assisted patency, and secondary
      patency were significantly better in the BMS group. CIAs treated with covered
      stents were more likely at 1 year or longer to require repeated intervention
      (hazard ratio, 2.5; 95% confidence interval, 1.2-5.3; P = .009). TASC
      classification did not predict need for reintervention in either group.
      Multivariate analysis revealed dual antiplatelet therapy to be the only other
      factor to affect patency during long-term follow-up. CONCLUSIONS: In this study,
      BMSs had significantly better patency compared with CBE stents for treatment of
      aortoiliac occlusive disease. A randomized trial comparing patency as well as
      restenosis rates with long-term follow-up is needed to determine if there is any
      benefit from use of covered stents in the aortoiliac segment.

PMID- 24725910
TI  - Efficacy of shared decision making on treatment satisfaction for patients with
      first-admission schizophrenia: study protocol for a randomised controlled trial.
AB  - BACKGROUND: Shared decision making is a promising model for patient-centred
      medicine, resulting in better clinical outcomes overall. In the mental health
      field, interventions that consider the patient-centred perspective--such as
      patient quality of life, involvement in the treatment, treatment satisfaction,
      and working alliance--have increased and better clinical outcomes discovered for
      patients with schizophrenia. However, few studies have examined the efficacy of
      shared decision making for schizophrenia treatment. The objective of this study
      is to evaluate the effect of a shared decision making intervention compared to
      treatment as usual on patient satisfaction at discharge for first-admission
      patients with schizophrenia. METHODS/DESIGN: This is a randomised, parallel
      group, two-arm, open-label, single-centre study currently being conducted in an
      acute psychiatric ward of Numazu Chuo Hospital, Japan. We are recruiting patients
      between 16 and 65 years old who are admitted to the ward with a diagnosis of
      schizophrenia without prior experience of psychiatric admission. Fifty-eight
      participants are being randomised into a shared decision making intervention
      group or a treatment as usual control group in a 1:1 ratio. The intervention
      program was developed based on a shared decision making model and is presented as
      a weekly course lasting the duration of the patients' acute psychiatric ward
      stay. The primary outcome measure is patient satisfaction at discharge as
      assessed by the Client Satisfaction Questionnaire. Due to the study's nature,
      neither the patient nor staff can be blinded. DISCUSSION: This is the first
      randomised controlled trial to evaluate the efficacy of shared decision making
      for patients with early-treatment-stage schizophrenia. The intervention program
      in this study is innovative in that it includes both of the patient and staff who
      are involved in the treatment. TRIAL REGISTRATION: The study has been registered
      with ClinicalTrials.gov as NCT01869660.

PMID- 24725911
TI  - Automated classifiers for early detection and diagnosis of retinopathy in
      diabetic eyes.
AB  - BACKGROUND: Artificial neural networks (ANNs) have been used to classify eye
      diseases, such as diabetic retinopathy (DR) and glaucoma. DR is the leading cause
      of blindness in working-age adults in the developed world. The implementation of
      DR diagnostic routines could be feasibly improved by the integration of
      structural and optical property test measurements of the retinal structure that
      provide important and complementary information for reaching a diagnosis. In this
      study, we evaluate the capability of several structural and optical features
      (thickness, total reflectance and fractal dimension) of various intraretinal
      layers extracted from optical coherence tomography images to train a Bayesian ANN
      to discriminate between healthy and diabetic eyes with and with no mild
      retinopathy. RESULTS: When exploring the probability as to whether the subject's
      eye was healthy (diagnostic condition, Test 1), we found that the structural and
      optical property features of the outer plexiform layer (OPL) and the complex
      formed by the ganglion cell and inner plexiform layers (GCL + IPL) provided the
      highest probability (positive predictive value (PPV) of 91% and 89%,
      respectively) for the proportion of patients with positive test results (healthy
      condition) who were correctly diagnosed (Test 1). The true negative, TP and PPV
      values remained stable despite the different sizes of training data sets (Test
      2). The sensitivity, specificity and PPV were greater or close to 0.70 for the
      retinal nerve fiber layer's features, photoreceptor outer segments and retinal
      pigment epithelium when 23 diabetic eyes with mild retinopathy were mixed with 38
      diabetic eyes with no retinopathy (Test 3). CONCLUSIONS: A Bayesian ANN trained
      on structural and optical features from optical coherence tomography data can
      successfully discriminate between healthy and diabetic eyes with and with no
      retinopathy. The fractal dimension of the OPL and the GCL + IPL complex predicted
      by the Bayesian radial basis function network provides better diagnostic utility
      to classify diabetic eyes with mild retinopathy. Moreover, the thickness and
      fractal dimension parameters of the retinal nerve fiber layer, photoreceptor
      outer segments and retinal pigment epithelium show promise for the diagnostic
      classification between diabetic eyes with and with no mild retinopathy.

PMID- 24725912
TI  - Surgery of the external nasal valve: the correlation between subjective and
      objective measurements.
AB  - OBJECTIVES/HYPOTHESIS: Minimum cross-sectional area of the nasal passage on CT
      (CT-MCA) is an objective computerised determination of the minimum cross
      sectional area of the nasal passage on CT. CT-MCA was evaluated before and after
      surgery on the external nasal valve using the 'lateral crus pull-up' procedure
      (LCPU). The outcomes of CT-MCA were compared with other currently available
      objective tests for nasal valve patency. STUDY DESIGN: Prospective cohort study.
      METHODS: This study included 34 patients undergoing surgery on the external nasal
      valve with the use of the LCPU technique. CT-MCA was performed before and after
      surgery and compared with the subjective perception of nasal passage using the
      Nasal Obstruction Symptom Evaluation (NOSE) scale and with objective tests such
      as acoustic rhinometry (A-MCA), rhinomanometry (NAR) and peak nasal inspiratory
      flow (PNIF). RESULTS: This study showed a significant correlation between CT-MCA
      and the NOSE scale, PNIF and NAR. Paired-samples t-tests showed significant
      improvement after surgery on CT-MCA, PNIF and the NOSE scale. Multiple linear
      regression analysis showed that PNIF, CT-MCA and NAR were significantly
      associated with the NOSE scale. CONCLUSION: CT-MCA and PNIF were both
      significantly correlated and associated with the patient's subjective perception
      of nasal passage. The surgical procedure, the 'lateral crus pull-up', showed a
      significant improvement in the postoperative result both subjectively and
      objectively.

PMID- 24725913
TI  - Prevalence and distribution of Aggregatibacter actinomycetemcomitans and its cdtB
      gene in subgingival plaque of Chinese periodontitis patients.
AB  - BACKGROUND: Aggregatibacter actinomycetemcomitans (A.actinomycetemcomitans) is an
      important periodontal pathogen that can participate in periodontitis and other
      non-oral infections. The cytolethal distending toxin (Cdt) is among the virulence
      factors produced by this bacterium. This study was to elucidate the distribution
      of A.actinomycetemcomitans and the prevalence of its cdtB gene in Chinese
      subjects. METHODS: A total of 255 subgingival samples were obtained from 30
      subjects. Samples were collected from periodontal healthy sites as well as
      shallow, moderate and deep pockets. The absolute quantity of
      A.actinomycetemcomitans and cdtB gene were determined by real-time polymerase
      chain reaction. RESULTS: A.actinomycetemcomitans was detected in 92 of 105
      (87.6%) samples of aggressive periodontitis (AgP) patients, in 73 of 79 (92.4%)
      samples of chronic periodontitis ( CP) patients and in 5 of 71 (7.0%) samples of
      periodontal healthy subjects. The cdtB gene was detected in 72 sites (78.3%) with
      AgP infected with A.actinomycetemcomitans, 54 sites (74.0%) with CP infected with
      A.actinomycetemcomitans and none in healthy sites infected with
      A.actinomycetemcomitans. In addition, quantity of A.actinomycetemcomitans and cdt
      gene in samples from deep pockets were significant larger than moderate, shallow
      and healthy sites (P < 0.05). In comparison to CP, AgP patients were infected
      with increased numbers of cdt genotype in deep pockets (P < 0.05). CONCLUSION:
      This study suggests that the cdtB gene are prevalent in A.actinomycetemcomitans,
      and the distribution of cdt genotype strain may be correlated with AgP and
      serious periodontal inflammation.

PMID- 24725914
TI  - Impact of availability of guidelines and active surveillance in reducing the
      incidence of ventilator-associated pneumonia in Europe and worldwide.
AB  - BACKGROUND: To analyse whether the availability of written standards for
      management of mechanically ventilated patients and/or the existence of a
      surveillance system for cases of ventilation-associated pneumonia (VAP) are
      positively associated with compliance with 6 well-established VAP prevention
      measures. METHODS: Ecological study based on responses to an online-questionnaire
      completed by 1730 critical care physicians. Replies were received from 77
      different countries, of which the majority, i.e. 1351, came from 36 European
      countries. RESULTS: On a cross-country level, compliance with VAP prevention
      measures is higher in countries with a large number of prevention standards
      and/or VAP surveillance systems in place at ICU level., Likewise, implementation
      of standards and VAP surveillance systems has a significant impact on self
      reported total compliance with VAP prevention measures (both p < 0.001).
      Moreover, predictions of overall prevention measure compliance show the effect
      size of the availability of written standards and existence of surveillance
      system. For instance, a female physician with 10 years of experience in critical
      care working in a 15-bed ICU in France has a predicted baseline level of VAP
      prevention measure compliance of 63 per cent. This baseline level increases by
      9.5 percentage points (p < 0.001) if a written clinical VAP prevention standard
      is available in the ICU, and by another 4 percentage points (p < 0.001) if
      complemented by a VAP surveillance system. CONCLUSIONS: The existence of written
      standards for management of mechanically ventilated patients in an ICU and the
      availability of VAP surveillance systems have shown to be positively associated
      with compliance with VAP prevention measures and should be fostered on a policy
      level.

PMID- 24725915
TI  - Lipid-lowering guidelines and statin use in CKD: a time for change.

PMID- 24725916
TI  - Advance care planning in CKD: clinical and research opportunities.

PMID- 24725917
TI  - Earlier- versus later-start peritoneal dialysis: not a moment too soon?

PMID- 24725918
TI  - Commentary on 'the DOPPS practice monitor for US dialysis care: potential impact
      of recent guidelines and regulatory changes on management of mineral and bone
      disorder among US hemodialysis patients': the calm before the 2016 storm?

PMID- 24725919
TI  - Validating GFR estimating samples with clinical outcomes.

PMID- 24725920
TI  - In reply to 'validating GFR estimating samples with clinical outcomes'.

PMID- 24725921
TI  - Quiz page may 2014: acute kidney injury with red urine.

PMID- 24725922
TI  - Inheritance of porcine receptors for enterotoxigenic Escherichia coli with
      fimbriae F4ad and their relation to other F4 receptors.
AB  - Enteric Escherichia coli infections are a highly relevant cause of disease and
      death in young pigs. Breeding genetically resistant pigs is an economical and
      sustainable method of prevention. Resistant pigs are protected against
      colonization of the intestine through the absence of receptors for the bacterial
      fimbriae, which mediate adhesion to the intestinal surface. The present work
      aimed at elucidation of the mode of inheritance of the F4ad receptor which
      according to former investigations appeared quite confusing. Intestines of 489
      pigs of an experimental herd were examined by a microscopic adhesion test
      modified in such a manner that four small intestinal sites instead of one were
      tested for adhesion of the fimbrial variant F4ad. Segregation analysis revealed
      that the mixed inheritance model explained our data best. The heritability of the
      F4ad phenotype was estimated to be 0.7+/-0.1. There are no relations to the
      strong receptors for variants F4ab and F4ac. Targeted matings allowed the
      discrimination between two F4ad receptors, that is, a fully adhesive receptor
      (F4adRFA) expressed on all enterocytes and at all small intestinal sites, and a
      partially adhesive receptor (F4adRPA) variably expressed at different sites and
      often leading to partial bacterial adhesion. In pigs with both F4ad receptors,
      the F4adRPA receptor is masked by the F4adRFA. The hypothesis that F4adRFA must
      be encoded by at least two complementary or epistatic dominant genes is supported
      by the Hardy-Weinberg equilibrium statistics. The F4adRPA receptor is inherited
      as a monogenetic dominant trait. A comparable partially adhesive receptor for
      variant F4ab (F4abRPA) was also observed but the limited data did not allow a
      prediction of the mode of inheritance. Pigs were therefore classified into one of
      eight receptor phenotypes: A1 (F4abRFA/F4acR+/F4adRFA); A2
      (F4abRFA/F4acR+/F4adRPA); B (F4abRFA/F4acR+/F4adR-); C1 (F4abRPA/F4acR-/F4adRFA);
      C2 (F4abRPA/F4acR-/F4adRPA); D1 (F4abR-/F4acR-/F4adRFA); D2 (F4abR-/F4acR
      /F4adRPA); E (F4abR-/F4acR-/F4adR-). 

PMID- 24725923
TI  - Submandibular puncture of the facial vein: an original route for endovascular
      therapy of cavernous sinus dural fistulas.
AB  - INTRODUCTION: Carotid cavernous sinus fistulas are a potentially severe
      pathology. Their basic standard treatment is an occlusion of the CCF performed by
      retrograde venous catheterization via the inferior petrous sinus. When the
      inferior petrous sinuses are occluded, other alternative venous routes are
      possible with various subsequent difficulties and risks. We report an original
      and safe method for endovascular treatment using submandibular puncture of the
      facial vein. CLINICAL CASES: We report 4 cases of patients with severe unilateral
      carotid cavernous sinus fistula associated with the occlusion of both inferior
      petrous sinuses. A submandibular surgical puncture of the ipsilateral inferior
      facial vein permitted the catheterization of the fistula. Complete occlusion of
      carotid cavernous sinus fistula was obtained by using a combination of microcoils
      and OnyxTM. DISCUSSION: When inferior petrous sinuses are occluded, endovascular
      treatment of carotid cavernous sinus fistulas is more difficult. After reviewing
      the other treatment options reported in the literature and their respective
      advantages and adverse effects, we describe an original technique based on the
      surgical puncture of the ipsilateral facial vein. The occlusion of the fistula is
      then obtained by using a combination of microcoils and OnyxTM. CONCLUSION: When
      the inferior petrous sinuses are occluded, an endovascular treatment for a
      carotid cavernous sinus fistula can be performed using an original and secure
      method. This method relies on a simple surgical puncture of the facial vein in
      the submandibular region, which then permits a retrograde catheterization of the
      carotid cavernous sinus fistula with no significant risk.

PMID- 24725924
TI  - Clinical characteristics and functions of non-suicide self-injury in youth.
AB  - PURPOSE: Little is known about the clinical characteristics and motivations for
      engaging in non-suicide self-injury (NSSI) behaviors in adolescence. The aim of
      this study was to examine the prevalence, characteristics and functions of NSSI
      among adolescents in community settings, and to explore risk factors related to
      this behavior. SUBJECTS AND METHODS: Two hundred and seventy-five adolescents
      aged 12 to 17 were recruited randomly from different High Schools in Israel. They
      completed self-report questionnaires assessing NSSI (Ottawa Self-Injury
      Inventory), depression (Children's Depression Inventory - CDI) and impulsivity
      (Barratt Impulsiveness Scale - BIS-II). RESULTS: In the past year, 20.7% of the
      participants reported engaging NSSI at least once. Among them, 42.1% declared
      they are still engaging in NSSI at the present. Motives for NSSI were internal
      emotion regulation reasons, external emotion regulation reasons for social
      influences. In addition, the NSSI group reported significantly higher levels of
      depressive, impulsivity and suicidal ideations. Depressive symptoms were found as
      significant predictors of NSSI in the future. DISCUSSION AND CONCLUSIONS: High
      rates of NSSI among community adolescents were found. Depression, impulsivity and
      suicidal ideation were found significantly related to NSSI. Mental health
      professionals in schools and in primary care should routinely assess NSSI among
      adolescents.

PMID- 24725925
TI  - Garlic in health and disease.
AB  - The present article reviews the historical and popular uses of garlic, its
      antioxidant, haematological, antimicrobial, hepatoprotective and antineoplastic
      properties and its potential toxicity (from sulfoxide). Garlic has been suggested
      to affect several cardiovascular risk factors. It has also been shown that garlic
      and its organic allyl sulfur components are effective inhibitors of the cancer
      process. Since garlic and its constituents can suppress carcinogen formation,
      bioactivation and tumour proliferation, it is imperative that biomarkers be
      established to identify which individuals might benefit most. Garlic powder, aged
      garlic and garlic oil have demonstrated antiplatelet and anticoagulant effects by
      interfering with cyclo-oxygenase-mediated thromboxane synthesis. Garlic has also
      been found to have synergistic effects against Helicobacter pylori with a proton
      pump inhibitor. The active compound allicin may affect atherosclerosis not only
      by acting as an antioxidant, but also by other mechanisms, such as lipoprotein
      modification and inhibition of LDL uptake and degradation by macrophages. Freshly
      prepared garlic homogenate protects against isoniazid+rifampicin-induced liver
      injury in experimental animal models. Several mechanisms are likely to account
      for this protection. 

PMID- 24725926
TI  - Presence of poly(A) and poly(A)-rich tails in a positive-strand RNA virus known
      to lack 3' poly(A) tails.
AB  - Here we show that Tobacco mosaic virus (TMV), a positive-strand RNA virus known
      to end with 3' tRNA-like structures, does possess a small fraction of gRNA
      bearing polyadenylate tails. Particularly, many tails are at sites corresponding
      to the 3' end of near full length gRNA, and are composed of poly(A)-rich
      sequences containing the other nucleotides in addition to adenosine, resembling
      the degradation-stimulating poly(A) tails observed in all biological kingdoms.
      Further investigations demonstrate that these polyadenylated RNA species are not
      enriched in chloroplasts. Silencing of cpPNPase, a chloroplast-localized
      polynucleotide polymerase known to not only polymerize the poly(A)-rich tails but
      act as a 3' to 5' exoribonuclease, does not change the profile of polyadenylate
      tails associated with TMV RNA. Nevertheless, because similar tails were also
      detected in other phylogenetically distinct positive-strand RNA viruses lacking
      poly(A) tails, such kind of polyadenylation may reflect a common but as-yet
      unknown interface between hosts and viruses.

PMID- 24725927
TI  - HIV-1 mutates to evade IFITM1 restriction.
AB  - Interferon-induced transmembrane (IFITM) proteins inhibit the infection of a wide
      range of viruses including human immunodeficiency virus type 1 (HIV-1). At
      present, little is known about how viruses overcome IFITM restriction. In this
      study, we have utilized HIV-1 as a model and selected IFITM1-resistant viruses
      after multiple passages of HIV-1 in IFITM1-expressing SupT1 cells. Sequencing the
      entire viral genome revealed several mutations in the vpu and envelope genes,
      among which mutations Vpu34 and EnvG367E together enable efficient HIV-1
      replication in IFITM1-expressing cells. Vpu34 introduces a stop codon at amino
      acid position 35 of Vpu, whereas EnvG367E changes the G367 residue at the CD4
      binding site of gp120. These two mutations do not appear to overcome the
      downregulation of viral p24 expression caused by IFITM1, but rather enhance HIV-1
      replication by promoting cell-to-cell virus transmission. Altogether, our data
      demonstrate that HIV-1 can mutate to evade IFITM1 restriction by increasing cell
      to-cell transmission.

PMID- 24725929
TI  - Constraints from protein structure and intra-molecular coevolution influence the
      fitness of HIV-1 recombinants.
AB  - A major challenge for developing effective treatments for HIV-1 is the viruses'
      ability to generate new variants. Inter-strain recombination is a major
      contributor to this high evolutionary rate, since at least 20% of viruses are
      observed to be recombinant. However, the patterns of recombination vary across
      the viral genome. A number of factors influence recombination, including sequence
      identity and secondary RNA structure. In addition the recombinant genome must
      code for a functional virus, and expressed proteins must fold to stable and
      functional structures. Any intragenic recombination that disrupts internal
      residue contacts may therefore produce an unfolded protein. Here we find that
      contact maps based on protein structures predict recombination breakpoints
      observed in the HIV-1 pandemic. Moreover, many pairs of contacting residues that
      are unlikely to be disrupted by recombination are coevolving. We conclude that
      purifying selection arising from protein structure and intramolecular
      coevolutionary changes shapes the observed patterns of recombination in HIV-1. 

PMID- 24725928
TI  - Discovery of rosavirus 2, a novel variant of a rodent-associated picornavirus, in
      children from The Gambia.
AB  - We describe the identification of a novel picornavirus recovered from the fecal
      specimen of a child in The Gambia, provisionally named rosavirus 2. Comparison of
      the rosavirus 2 complete genome demonstrated 71.9% nucleotide identity to its
      closest relative rosavirus M-7, an unclassified picornavirus identified from
      rodent fecal material. A unique RNA structure was predicted in the 3' UTR of
      rosavirus 2 that was conserved with rosavirus M-7 and cadiciviruses. We detected
      rosavirus 2 in four pediatric fecal specimens (0.55% prevalence) in a Gambian
      diarrheal case-control cohort, but we did not detect it in a panel of 634
      pediatric diarrheal stool specimens from the USA. There was no statistical
      evidence that rosavirus 2 was associated with diarrheal cases. This study
      broadens our understanding of unknown viruses present in children in developing
      country settings. 

PMID- 24725930
TI  - Large-scale analysis of influenza A virus nucleoprotein sequence conservation
      reveals potential drug-target sites.
AB  - The nucleoprotein (NP) of the influenza A virus encapsidates the viral RNA and
      participates in the infectious life cycle of the virus. The aims of this study
      were to find the degree of conservation of NP among all virus subtypes and hosts
      and to identify conserved binding sites, which may be utilised as potential drug
      target sites. The analysis of conservation based on 4430 amino acid sequences
      identified high conservation in known functional regions as well as novel highly
      conserved sites. Highly variable clusters identified on the surface of NP may be
      associated with adaptation to different hosts and avoidance of the host immune
      defence. Ligand binding potential overlapping with high conservation was found in
      the tail-loop binding site and near the putative RNA binding region. The results
      provide the basis for developing antivirals that may be universally effective and
      have a reduced potential to induce resistance through mutations. 

PMID- 24725931
TI  - Effective inhibition of Japanese encephalitis virus replication by shRNAs
      targeting various viral genes in vitro and in vivo.
AB  - Japanese encephalitis virus (JEV) is a serious mosquito-borne flavivirus that
      causes acute encephalitis in humans and many animals, with a high fatality rate.
      RNA interference (RNAi) is an evolutionarily conserved mechanism for the specific
      suppression of gene expression, which can be used as a reasonable antiviral
      strategy. In this study, 10 shRNAs targeting different regions of the JEV genome
      were designed, and their inhibition of viral replication in vitro and in vivo was
      determined. Treatment with these shRNAs significantly inhibited JEV replication
      in BHK-21 and SK-N-SH cells. An immunohistochemical analysis of suckling mice
      showed that brain sections pretreated with pGP-JE-1, pGP-JE-2 or pGP-JE-3 lacked
      viral particles. The survival of BALB/c mice challenged with 20 LD50 of the JEV
      NJ2008 strain at 24h post-injection or simultaneously with pGP-JE-2 was 83.3% and
      66.7%, respectively. The results demonstrated that the efficiency of gene
      silencing and virus inhibition varied between shRNAs to different target genes
      and sites. Meanwhile, the shRNA-mediated antiviral effect was dose- and time
      dependent, including prophylactic and therapeutic effect on virus infection both
      in vitro and in vivo. The whole results indicate that these shRNAs can inhibit
      JEV infection sufficiently in vitro and in vivo and might be a potential new tool
      for controlling JEV infection.

PMID- 24725932
TI  - Nuclear trafficking of the HIV-1 pre-integration complex depends on the ADAM10
      intracellular domain.
AB  - Previously, we showed that ADAM10 is necessary for HIV-1 replication in primary
      human macrophages and immortalized cell lines. Silencing ADAM10 expression
      interrupted the HIV-1 life cycle prior to nuclear translocation of viral cDNA.
      Furthermore, our data indicated that HIV-1 replication depends on the expression
      of ADAM15 and gamma-secretase, which proteolytically processes ADAM10. Silencing
      ADAM15 or gamma-secretase expression inhibits HIV-1 replication between reverse
      transcription and nuclear entry. Here, we show that ADAM10 expression also
      supports replication in CD4(+) T lymphocytes. The intracellular domain (ICD) of
      ADAM10 associates with the HIV-1 pre-integration complex (PIC) in the cytoplasm
      and immunoprecipitates and co-localizes with HIV-1 integrase, a key component of
      PIC. Taken together, our data support a model whereby ADAM15/gamma-secretase
      processing of ADAM10 releases the ICD, which then incorporates into HIV-1 PIC to
      facilitate nuclear trafficking. Thus, these studies suggest ADAM10 as a novel
      therapeutic target for inhibiting HIV-1 prior to nuclear entry.

PMID- 24725933
TI  - The interaction of the HSV-1 tegument proteins pUL36 and pUL37 is essential for
      secondary envelopment during viral egress.
AB  - The herpes simplex virus type 1 (HSV-1) tegument proteins pUL36 (VP1/2) and pUL37
      are essential for viral egress. We previously defined a minimal domain in HSV-1
      pUL36, residues 548-572, as important for binding pUL37. Here, we investigated
      the role of this region in binding to pUL37 and facilitating viral replication.
      We deleted residues 548-572 in frame in a virus containing a mRFP tag at the N
      terminus of the capsid protein VP26 and an eGFP tag at the C-terminus of pUL37
      (HSV-1pUL36?548-572). This mutant virus was unable to generate plaques in Vero
      cells, indicating that deletion of this region of pUL36 blocks viral replication.
      Imaging of HSV-1pUL36?548-572-infected Vero cells, in comparison to parental and
      resucant, revealed a block in secondary envelopment of cytoplasmic capsids. In
      addition, immunoblot analysis suggested that failure to bind pUL37 affected the
      stability of pUL36. This study provides further insight into the role of this
      essential interaction.

PMID- 24725934
TI  - Lack of group X secreted phospholipase A2 increases survival following pandemic
      H1N1 influenza infection.
AB  - The role of Group X secreted phospholipase A2 (GX-sPLA2) during influenza
      infection has not been previously investigated. We examined the role of GX-sPLA2
      during H1N1 pandemic influenza infection in a GX-sPLA2 gene targeted mouse (GX(-/
      )) model and found that survival after infection was significantly greater in GX(
      /-) mice than in GX(+/+) mice. Downstream products of GX-sPLA2 activity, PGD2,
      PGE2, LTB4, cysteinyl leukotrienes and Lipoxin A4 were significantly lower in GX(
      /-) mice BAL fluid. Lung microarray analysis identified an earlier and more
      robust induction of T and B cell associated genes in GX(-/-) mice. Based on the
      central role of sPLA2 enzymes as key initiators of inflammatory processes, we
      propose that activation of GX-sPLA2 during H1N1pdm infection is an early step of
      pulmonary inflammation and its inhibition increases adaptive immunity and
      improves survival. Our findings suggest that GX-sPLA2 may be a potential
      therapeutic target during influenza.

PMID- 24725935
TI  - Structural models of the membrane anchors of envelope glycoproteins E1 and E2
      from pestiviruses.
AB  - The membrane anchors of viral envelope proteins play essential roles in cell
      entry. Recent crystal structures of the ectodomain of envelope protein E2 from a
      pestivirus suggest that E2 belongs to a novel structural class of membrane fusion
      machinery. Based on geometric constraints from the E2 structures, we generated
      atomic models of the E1 and E2 membrane anchors using computational approaches.
      The E1 anchor contains two amphipathic perimembrane helices and one transmembrane
      helix; the E2 anchor contains a short helical hairpin stabilized in the membrane
      by an arginine residue, similar to flaviviruses. A pair of histidine residues in
      the E2 ectodomain may participate in pH sensing. The proposed atomic models point
      to Cys987 in E2 as the site of disulfide bond linkage with E1 to form E1-E2
      heterodimers. The membrane anchor models provide structural constraints for the
      disulfide bonding pattern and overall backbone conformation of the E1 ectodomain.

PMID- 24725936
TI  - Analysis of viral microRNA expression by elephant endotheliotropic herpesvirus 1.
AB  - Elephant endotheliotropic herpesvirus 1 (EEHV1), a member of the
      Betaherpesvirinae subfamily, has recently emerged as an important viral pathogen
      of Asian elephants that can cause a severe, often fatal, hemorrhagic disease.
      EEHV1 does not replicate in culture and little is currently known about the
      molecular biology of this emerging pathogen, with the notable exception of its
      genomic DNA sequence. Here, we have used small RNA deep sequencing to determine
      whether EEHV1, like other human and murine betaherpesviruses, expresses viral
      microRNAs in infected tissues in vivo. Our data provide evidence supporting the
      existence of at least three novel viral microRNAs encoded by EEHV1 and one of
      these, miR-E3-5p, is shown to repress target mRNA expression. Moreover, miR-E3-5p
      expression was readily detectable in tissue samples derived from two infected
      elephants, including in whole blood. These data shed new light on the biology of
      EEHV1 and identify small RNAs that have the potential to be useful in the
      diagnosis of sub-clinical infections in captive Asian and African elephants.

PMID- 24725937
TI  - The V domain of dog PVRL4 (nectin-4) mediates canine distemper virus entry and
      virus cell-to-cell spread.
AB  - The entry of canine distemper virus (CDV) is a multistep process that involves
      the attachment of CDV hemagglutinin (H) to its cellular receptor, followed by
      fusion between virus and cell membranes. Our laboratory recently identified PVRL4
      (nectin-4) to be the epithelial receptor for measles and canine distemper
      viruses. In this study, we demonstrate that the V domain of PVRL4 is critical for
      CDV entry and virus cell-to-cell spread. Furthermore, four key amino acid
      residues within the V domain of dog PVRL4 and two within the CDV hemagglutinin
      were shown to be essential for receptor-mediated virus entry.

PMID- 24725939
TI  - Exposure of human astrocytes to leukotriene C4 promotes a CX3CL1/fractalkine
      mediated transmigration of HIV-1-infected CD4+ T cells across an in vitro blood
      brain barrier model.
AB  - Eicosanoids, including cysteinylleukotrienes (cysLTs), are found in the central
      nervous system (CNS) of individuals infected with HIV-1. Few studies have
      addressed the contribution of cysLTs in HIV-1-associated CNS disorders. We
      demonstrate that conditioned medium from human astrocytes treated with
      leukotriene C4 (LTC4) increases the transmigration of HIV-1-infected CD4(+) T
      cells across an in vitro blood-brain barrier (BBB) model using cultured brain
      endothelial cells. Additional studies indicate that the higher cell migration is
      linked with secretion by astrocytes of CX3CL1/fractalkine, a chemokine that has
      chemoattractant activity for CD4(+) T cells. Moreover, we report that the
      enhanced cell migration across BBB leads to a more important CD4(+) T cell
      mediated HIV-1 transfer toward macrophages. Altogether data presented in the
      present study reveal the important role that LTC4, a metabolite of arachidonic
      acid, may play in the HIV-1-induced neuroinvasion, neuropathogenesis and disease
      progression.

PMID- 24725938
TI  - The NS5A-binding heat shock proteins HSC70 and HSP70 play distinct roles in the
      hepatitis C viral life cycle.
AB  - We previously identified HSP70 and HSC70 in complex with NS5A in a proteomic
      screen. Here, coimmunoprecipitation studies confirmed NS5A/HSC70 complex
      formation during infection, and immunofluorescence studies showed NS5A and HSC70
      to colocalize. Unlike HSP70, HSC70 knockdown did not decrease viral protein
      levels. Rather, intracellular infectious virion assembly was significantly
      impaired by HSC70 knockdown. We also discovered that both HSC70 nucleotide
      binding and substrate binding domains directly bind NS5A whereas only the HSP70
      nucleotide binding domain does. Knockdown of both HSC70 and HSP70 demonstrated an
      additive reduction in virus production. This data suggests that HSC70 and HSP70
      play discrete roles in the viral life cycle. Investigation of these different
      functions may facilitate developing of novel strategies that target host proteins
      to treat HCV infection.

PMID- 24725940
TI  - Escape from neutralization by the respiratory syncytial virus-specific
      neutralizing monoclonal antibody palivizumab is driven by changes in on-rate of
      binding to the fusion protein.
AB  - The role of binding kinetics in determining neutralizing potency for antiviral
      antibodies is poorly understood. While it is believed that increased steady-state
      affinity correlates positively with increased virus-neutralizing activity, the
      relationship between association or dissociation rate and neutralization potency
      is unclear. We investigated the effect of naturally-occurring antibody resistance
      mutations in the RSV F protein on the kinetics of binding to palivizumab. Escape
      from palivizumab-mediated neutralization of RSV occurred with reduced association
      rate (Kon) for binding to RSV F protein, while alteration of dissociation rate
      (Koff) did not significantly affect neutralizing activity. Interestingly, linkage
      of reduced Kon with reduced potency mirrored the effect of increased Kon found in
      a high-affinity enhanced potency palivizumab variant (motavizumab). These data
      suggest that association rate is the dominant factor driving neutralization
      potency for antibodies to RSV F protein antigenic site A and determines the
      potency of antibody somatic variants or efficiency of escape of viral
      glycoprotein variants.

PMID- 24725941
TI  - Determination of the protease cleavage site repertoire--the RNase H but not the
      RT domain is essential for foamy viral protease activity.
AB  - In contrast to orthoretroviruses, the foamy virus protease is only active as a
      protease-reverse transcriptase fusion protein and requires viral RNA for
      activation. Maturation of foamy viral proteins seems to be restricted to a single
      cleavage site in Gag and Pol. We provide evidence that unprocessed Gag is
      required for optimal infectivity, which is unique among retroviruses. Analyses of
      the cleavage site sequences of the Gag and Pol cleavage sites revealed a high
      similarity compared to those of Lentiviruses. We show that positions P2' and P2
      are invariant and that Gag and Pol cleavage sites are processed with similar
      efficiencies. The RNase H domain is essential for protease activity, but can
      functionally be substituted by RNase H domains of other retroviruses. Thus, the
      RNase H domain might be involved in the stabilization of the protease dimer,
      while the RT domain is essential for RNA dependent protease activation. 

PMID- 24725942
TI  - Phagocytic cells contribute to the antibody-mediated elimination of pulmonary
      infected SARS coronavirus.
AB  - While the 2002-2003 outbreak of severe acute respiratory syndrome (SARS) resulted
      in 774 deaths, patients who were affected with mild pulmonary symptoms
      successfully recovered. The objective of the present work was to identify, using
      SARS coronavirus (SARS-CoV) mouse infection models, immune factors responsible
      for clearing of the virus. The elimination of pulmonary SARS-CoV infection
      required the activation of B cells by CD4(+) T cells. Furthermore, passive
      immunization (post-infection) with homologous (murine) anti-SARS-CoV antiserum
      showed greater elimination efficacy against SARS-CoV than that with heterologous
      (rabbit) antiserum, despite the use of equivalent titers of neutralizing
      antibodies. This distinction was mediated by mouse phagocytic cells (monocyte
      derived infiltrating macrophages and partially alveolar macrophages, but not
      neutrophils), as demonstrated both by adoptive transfer from donors and by
      immunological depletion of selected cell types. These results indicate that the
      cooperation of anti-SARS-CoV antibodies and phagocytic cells plays an important
      role in the elimination of SARS-CoV.

PMID- 24725943
TI  - Evaluation of the antigenic relatedness and cross-protective immunity of the
      neuraminidase between human influenza A (H1N1) virus and highly pathogenic avian
      influenza A (H5N1) virus.
AB  - To determine the genetic and antigenic relatedness as well as the cross
      protective immunity of human H1N1 and avian H5N1 influenza virus neuraminidase
      (NA), we immunized rabbits with either a baculovirus-expressed recombinant NA
      from A/Beijing/262/95 (BJ/262) H1N1 or A/Hong Kong/483/97 (HK/483) H5N1 virus.
      Cross-reactive antibody responses were evaluated by multiple serological assays
      and cross-protection against H5N1 virus challenge was evaluated in mice. In a
      neuraminidase inhibition (NI) test, the antisera exhibited substantial inhibition
      of NA activity of the homologous virus, but failed to inhibit the NA activity of
      heterologous virus. However, these antisera exhibited low levels of cross
      reactivity measured by plaque size reduction, replication inhibition, single
      radial hemolysis, and ELISA assays. Passive immunization with HK/483 NA-specific
      antisera significantly reduced virus replication and disease, and afforded almost
      complete protection against lethal homologous virus challenge in mice. However,
      passive immunization with BJ/262 (H1N1) NA-specific antisera was ineffective at
      providing cross-protection against lethal H5N1 virus challenge and only slightly
      reduced weight loss. Substantial amino acid variation among the NA antigenic
      sites was observed between BJ/262 and HK/483 virus, which was consistent with the
      lack of cross-reactive NI activity by the antibody and limited cross-protective
      immunity in mice. These results show a strong correlation between the lack of
      cross-protective immunity and low structural similarities of NA from a human
      seasonal H1N1 virus and an avian H5N1 influenza virus.

PMID- 24725944
TI  - Characterization of viral siRNA populations in honey bee colony collapse
      disorder.
AB  - Colony Collapse Disorder (CCD), a special case of collapse of honey bee colonies,
      has resulted in significant losses for beekeepers. CCD-colonies show abundance of
      pathogens which suggests that they have a weakened immune system. Since honey bee
      viruses are major players in colony collapse and given the important role of
      viral RNA interference (RNAi) in combating viral infections we investigated if
      CCD-colonies elicit an RNAi response. Deep-sequencing analysis of samples from
      CCD-colonies from US and Israel revealed abundant small interfering RNAs (siRNA)
      of 21-22 nucleotides perfectly matching the Israeli acute paralysis virus (IAPV),
      Kashmir virus and Deformed wing virus genomes. Israeli colonies showed high
      titers of IAPV and a conserved RNAi-pattern of matching the viral genome. That
      was also observed in sample analysis from colonies experimentally infected with
      IAPV. Our results suggest that CCD-colonies set out a siRNA response that is
      specific against predominant viruses associated with colony losses. 

PMID- 24725945
TI  - Immunological alterations and associated diseases in mandrills (Mandrillus
      sphinx) naturally co-infected with SIV and STLV.
AB  - Mandrills are naturally infected with simian T-cell leukaemia virus type 1 (STLV
      1) and simian immunodeficiency virus (SIV)mnd. In humans, dual infection with
      human immunodeficiency virus (HIV) and human T-cell lymphotropic virus type 1
      (HTLV-1) may worsen their clinical outcome. We evaluated the effect of co
      infection in mandrills on viral burden, changes in T-cell subsets and clinical
      outcome. The SIV viral load was higher in SIV-infected mandrills than in co
      infected animals, whereas the STLV-1 proviral load was higher in co-infected than
      in mono-infected groups. Dually infected mandrills had a statistically
      significantly lower CD4+ T-cell count, a lower proportion of naive CD8+ T cells
      and a higher proportion of central memory cells. CD4(+) and CD8(+) T cells from
      SIV-infected animals had a lower percentage of Ki67 than those from the other
      groups. Co-infected monkeys had higher percentages of activated CD4(+) and CD8(+)
      T cells. Two co-infected mandrills with high immune activation and clonal
      integration of STLV provirus showed pathological manifestations (infective
      dermatitis and generalised scabies) rarely encountered in nonhuman primates. 

PMID- 24725946
TI  - Productive replication of Middle East respiratory syndrome coronavirus in
      monocyte-derived dendritic cells modulates innate immune response.
AB  - The Middle East respiratory syndrome coronavirus (MERS-CoV) closely resembled
      severe acute respiratory syndrome coronavirus (SARS-CoV) in disease manifestation
      as rapidly progressive acute pneumonia with multi-organ dysfunction. Using
      monocyte-derived-dendritic cells (Mo-DCs), we discovered fundamental
      discrepancies in the outcome of MERS-CoV- and SARS-CoV-infection. First, MERS-CoV
      productively infected Mo-DCs while SARS-CoV-infection was abortive. Second, MERS
      CoV induced significantly higher levels of IFN-gamma, IP-10, IL-12, and RANTES
      expression than SARS-CoV. Third, MERS-CoV-infection induced higher surface
      expression of MHC class II (HLA-DR) and the co-stimulatory molecule CD86 than
      SARS-CoV-infection. Overall, our data suggests that the dendritic cell can serve
      as an important target of viral replication and a vehicle for dissemination. MERS
      CoV-infection in DCs results in the production of a rich combination of cytokines
      and chemokines, and modulates innate immune response differently from that of
      SARS-CoV-infection. Our findings may help to explain the apparent discrepancy in
      the pathogenicity between MERS-CoV and SARS-CoV.

PMID- 24725947
TI  - Identification and characterization of multiple conserved nuclear localization
      signals within adenovirus E1A.
AB  - The human adenovirus 5 (HAdV-5) E1A protein has a well defined canonical nuclear
      localization signal (NLS) located at its C-terminus. We used a genetic assay in
      the yeast Saccharomyces cerevisiae to demonstrate that the canonical NLS is
      present and functional in the E1A proteins of each of the six HAdV species. This
      assay also detects a previously described non-canonical NLS within conserved
      region 3 and a novel active NLS within the N-terminal/conserved region 1 portion
      of HAdV-5 E1A. These activities were also present in the E1A proteins of each of
      the other five HAdV species. These results demonstrate that, despite substantial
      differences in primary sequence, HAdV E1A proteins are remarkably consistent in
      that they contain one canonical and two non-canonical NLSs. By utilizing
      independent mechanisms, these multiple NLSs ensure nuclear localization of E1A in
      the infected cell.

PMID- 24725949
TI  - AAV8 capsid variable regions at the two-fold symmetry axis contribute to high
      liver transduction by mediating nuclear entry and capsid uncoating.
AB  - Adeno-associated virus serotype 8 (AAV8) is a promising vector for liver-directed
      gene therapy. Although efficient uncoating of viral capsids has been implicated
      in AAV8's robust liver transduction, much about the biology of AAV8 hepatotropism
      remains unclear. Our study investigated the structural basis of AAV8 liver
      transduction efficiency by constructing chimeric vector capsids containing
      sequences derived from AAV8 and AAV2 - a highly homologous yet poorly
      hepatotropic serotype. Engineered vectors containing capsid variable regions (VR)
      VII & IX from AAV8 in an AAV2 backbone mediated near AAV8-like transduction in
      mouse liver, with higher numbers of chimeric genomes detected in whole liver
      cells and isolated nuclei. Interestingly, chimeric capsids within liver nuclei
      also uncoated similarly to AAV8 by 6 weeks after administration, in contrast with
      AAV2, of which a significantly smaller proportion were uncoated. This study links
      specific AAV capsid regions to the transduction ability of a clinically relevant
      AAV serotype.

PMID- 24725948
TI  - Host restriction of murine gammaherpesvirus 68 replication by human APOBEC3
      cytidine deaminases but not murine APOBEC3.
AB  - Humans encode seven APOBEC3 (A3A-A3H) cytidine deaminase proteins that differ in
      their expression profiles, preferred nucleotide recognition sequence and capacity
      for restriction of RNA and DNA viruses. We identified APOBEC3 hotspots in
      numerous herpesvirus genomes. To determine the impact of host APOBEC3 on
      herpesvirus biology in vivo, we examined whether murine APOBEC3 (mA3) restricts
      murine gammaherpesvirus 68 (MHV68). Viral replication was impaired by several
      human APOBEC3 proteins, but not mA3, upon transfection of the viral genome. The
      restriction was abrogated upon mutation of the A3A and A3B active sites.
      Interestingly, virus restriction by A3A, A3B, A3C, and A3DE was lost if the
      infectious DNA was delivered by the virion. MHV68 pathogenesis, including lung
      replication and splenic latency, was not altered in mice lacking mA3. We infer
      that mA3 does not restrict wild type MHV68 and restriction by human A3s may be
      limited in the herpesvirus replication process.

PMID- 24725950
TI  - Antibody neutralization of retargeted measles viruses.
AB  - The measles virus (MV) vaccine lineage is a promising oncolytic but prior
      exposure to the measles vaccine or wild-type MV strains limits treatment utility
      due to the presence of anti-measles antibodies. MV entry can be redirected by
      displaying a polypeptide ligand on the Hemagglutinin (H) C-terminus. We
      hypothesized that retargeted MV would escape neutralization by monoclonal
      antibodies (mAbs) recognizing the H receptor-binding surface and be less
      susceptible to neutralization by human antisera. Using chimeric H proteins, with
      and without mutations that ablate MV receptor binding, we show that retargeted
      MVs escape mAbs that target the H receptor-binding surface by virtue of mutations
      that ablate infection via SLAM and CD46. However, C-terminally displayed domains
      do not mediate virus entry in the presence of human antibodies that bind to the
      underlying H domain. In conclusion, utility of retargeted oncolytic measles
      viruses does not extend to evasion of human serum neutralization.

PMID- 24725951
TI  - The vOTU domain of highly-pathogenic porcine reproductive and respiratory
      syndrome virus displays a differential substrate preference.
AB  - Arterivirus genus member Porcine reproductive and respiratory syndrome virus
      (PRRSV) causes an economically devastating disease, recently exacerbated by the
      emergence of highly pathogenic strains (HP-PRRSV). Within the nonstructural
      protein 2 of PRRSV is a deubiquitinating enzyme domain belonging to the viral
      ovarian tumor (vOTU) protease superfamily. vOTUs, which can greatly vary in their
      preference for their host ubiquitin (Ub) and Ub-like substrates such as
      interferon stimulated gene 15 (ISG15), have been implicated as a potential
      virulence factor. Since various strains of PRRSV have large variations in
      virulence, the specificity of vOTUs from two PRRSV strains of varying virulence
      were determined. While both vOTUs showed de-ubiquitinating activity and markedly
      low deISGylating activity, HP-PRRSV demonstrated a strong preference for lysine
      63-linked poly-Ubiquitin, tied to innate immune response regulation. This
      represents the first report of biochemical activity unique to HP-PRRSV that has
      implications for a potential increase in immunosuppression and virulence.

PMID- 24725952
TI  - Homosubtypic and heterosubtypic antibodies against highly pathogenic avian
      influenza H5N1 recombinant proteins in H5N1 survivors and non-H5N1 subjects.
AB  - Six recombinant vaccinia viruses containing HA, NA, NP, M or NS gene insert
      derived from a highly pathogenic avian influenza H5N1 virus, and the recombinant
      vaccinia virus harboring plasmid backbone as the virus control were constructed.
      The recombinant proteins were characterized for their expression and subcellular
      locations in TK(-) cells. Antibodies to the five recombinant proteins were
      detected in all 13 sequential serum samples collected from four H5N1 survivors
      during four years of follow-up; and those directed to rVac-H5 HA and rVac-NA
      proteins were found in higher titers than those directed to the internal proteins
      as revealed by indirect immunofluorescence assay. Although all 28 non-H5N1
      subjects had no neutralizing antibodies against H5N1 virus, they did have cross
      reactive antibodies to those five recombinant proteins. A significant increase in
      cross-reactive antibody titer to rVac-H5 HA and rVac-NA was found in paired blood
      samples from patients infected with the 2009 pandemic virus. 

PMID- 24725953
TI  - Respiratory syncytial virus increases lung cellular bioenergetics in neonatal
      C57BL/6 mice.
AB  - We have previously reported that lung cellular bioenergetics (cellular
      respiration and ATP) increased in 4-10 week-old BALB/c mice infected with
      respiratory syncytial virus (RSV). This study examined the kinetics and changes
      in cellular bioenergetics in <= 2-week-old C57BL/6 mice following RSV infection.
      Mice (5-14 days old) were inoculated intranasally with RSV and the lungs were
      examined on days 1-10 post-infection. Histopathology and electron microscopy
      revealed preserved pneumocyte architectures and organelles. Increased lung
      cellular bioenergetics was noted from days 1-10 post-infection. Cellular GSH
      remained unchanged. These results indicate that the increased lung cellular
      respiration (measured by mitochondrial O2 consumption) and ATP following RSV
      infection is independent of either age or genetic background of the host.

PMID- 24725954
TI  - Rotavirus infection induces G1 to S phase transition in MA104 cells via
      Ca+2/Calmodulin pathway.
AB  - Viruses, obligate cellular parasites rely on host cellular functions and target
      the host cell cycle for their own benefit. In this study, effect of rotavirus
      infection on cell cycle machinery was explored. We found that rotavirus (RV)
      infection in MA104 cells induces the expression of cyclins and cyclin dependent
      kinases and down-regulates expression of CDK inhibitors, resulting in G1 to S
      phase transition. The rotavirus induced S phase accumulation was found to be
      concurrent with induction in expression of calmodulin and activation of CaMKI
      which is reported as inducer of G1-S phase transition. This cell cycle
      manipulation was found to be Ca(+2)/Calmodulin pathway dependent. The
      physiological relevance of G1 to S phase transition was established when viral
      gene expressions as well as viral titers were found to be increased in S phase
      synchronized cells and decreased in G0/G1 phase synchronized cells compared to
      unsynchronized cells during rotavirus infection.

PMID- 24725955
TI  - Differential segregation of nodaviral coat protein and RNA into progeny virions
      during mixed infection with FHV and NoV.
AB  - Nodaviruses are icosahedral viruses with a bipartite, positive-sense RNA genome.
      The two RNAs are packaged into a single virion by a poorly understood mechanism.
      We chose two distantly related nodaviruses, Flock House virus and Nodamura virus,
      to explore formation of viral reassortants as a means to further understand
      genome recognition and encapsidation. In mixed infections, the viruses were
      incompatible at the level of RNA replication and their coat proteins segregated
      into separate populations of progeny particles. RNA packaging, on the other hand,
      was indiscriminate as all four viral RNAs were detectable in each progeny
      population. Consistent with the trans-encapsidation phenotype, fluorescence in
      situ hybridization of viral RNA revealed that the genomes of the two viruses co
      localized throughout the cytoplasm. Our results imply that nodaviral RNAs lack
      rigorously defined packaging signals and that co-encapsidation of the viral RNAs
      does not require a pair of cognate RNA1 and RNA2.

PMID- 24725956
TI  - Positive selection of primate genes that promote HIV-1 replication.
AB  - Evolutionary analyses have revealed that most host-encoded restriction factors
      against HIV have experienced virus-driven selection during primate evolution.
      However, HIV also depends on the function of many human proteins, called host
      factors, for its replication. It is not clear whether virus-driven selection
      shapes the evolution of host factor genes to the extent that it is known to shape
      restriction factor genes. We show that five out of 40 HIV host factor genes (13%)
      analyzed do bear strong signatures of positive selection. Some of these genes
      (CD4, NUP153, RANBP2/NUP358) have been characterized with respect to the HIV
      lifecycle, while others (ANKRD30A/NY-BR-1 and MAP4) remain relatively
      uncharacterized. One of these, ANKRD30A, shows the most rapid evolution within
      this set of genes and is induced by interferon stimulation. We discuss how
      evolutionary analysis can aid the study of host factors for viral replication,
      just as it has the study of host immunity systems.

PMID- 24725957
TI  - Induction of stress granules by interferon and down-regulation by the cellular
      RNA adenosine deaminase ADAR1.
AB  - Measles virus (MV) deficient in C protein (C(ko)) expression efficiently induces
      both stress granules (SG) and interferon (IFNbeta), whereas isogenic wild-type
      (WT) and V mutant (V(ko)) viruses do not. We therefore examined the effect of
      IFNbeta pretreatment on SG formation, and the roles played by the IFN-inducible
      double-stranded (ds) RNA-dependent protein kinase (PKR) and dsRNA adenosine
      deaminase (ADAR1). SG formation in ADAR1-sufficient cells infected with WT or
      V(ko) mutant virus was enhanced by IFN treatment and was PKR-dependent. SG
      formation in C(ko) virus-infected cells was already high without IFN treatment
      and was not further enhanced by IFN. IFN treatment alone, in the absence of
      infection, induced SG formation in ADAR1-deficient but not ADAR1-sufficient
      cells. Type I IFN-induced enhancement in SG formation occurred by a canonical IFN
      signaling response dependent upon STAT1 and STAT2. These results further
      establish ADAR1 as a suppressor of the interferon and SG innate immune responses.

PMID- 24725958
TI  - Varicella-zoster virus induces the formation of dynamic nuclear capsid
      aggregates.
AB  - The first step of herpesviruses virion assembly occurs in the nucleus. However,
      the exact site where nucleocapsids are assembled, where the genome and the inner
      tegument are acquired, remains controversial. We created a recombinant VZV
      expressing ORF23 (homologous to HSV-1 VP26) fused to the eGFP and dually
      fluorescent viruses with a tegument protein additionally fused to a red tag
      (ORF9, ORF21 and ORF22 corresponding to HSV-1 UL49, UL37 and UL36). We identified
      nuclear dense structures containing the major capsid protein, the scaffold
      protein and maturing protease, as well as ORF21 and ORF22. Correlative microscopy
      demonstrated that the structures correspond to capsid aggregates and time-lapse
      video imaging showed that they appear prior to the accumulation of cytoplasmic
      capsids, presumably undergoing the secondary egress, and are highly dynamic. Our
      observations suggest that these structures might represent a nuclear area
      important for capsid assembly and/or maturation before the budding at the inner
      nuclear membrane.

PMID- 24725959
TI  - Genetic characterization of Toxoplasma gondii from cats in Yunnan Province,
      Southwestern China.
AB  - BACKGROUND: Cats are the definitive hosts of Toxoplasma gondii. The distribution
      of genetic diversity of T. gondii in cats is of importance to understand the
      transmission of this parasite. The objective of this study was to genetically
      characterize T. gondii isolates from cats in Yunnan province, southwestern China.
      METHODS: Genomic DNA was extracted from 5-10 g cat tissue samples (brain, tongue,
      heart, and liver). Using multilocous polymerase chain reaction-restriction
      fragment length polymorphism (PCR-RFLP) technology, we determined genetic
      diversity of T. gondii isolates from cats in Yunnan province. RESULT: In total,
      175 stray cats were tested for T. gondii DNA, respectively, 44 (25.14%) of which
      were found to be positive for the T. gondii B1 gene by PCR amplification. The
      positive DNA samples were typed at 11 genetic markers, including 10 nuclear
      markers, namely, SAG1, 5'-3'SAG2, alternative SAG2, SAG3, GRA6, L358, PK1, BTUB,
      c22-8, c29-2 and an apicoplast locus Apico. Of these, 16 isolates from cats were
      genotyped with data for more than 9 loci, revealed 5 genotypes in total, of which
      11 of 16 samples were identified as ToxoDB#9, two samples may belong to genotye
      #225, one was Type II, one was ToxoDB#3, and one was ToxoDB#20
      (http://toxodb.org/toxo/). CONCLUSIONS: The results of the present study
      indicated a wide distribution of T. gondii infection in cats in Yunnan province,
      which may pose significant public health concerns. To our knowledge, the present
      study is the first report of T. gondii prevalence and genotypes in cats in
      southwestern China, and the first report of Type II T. gondii from cats in China.

PMID- 24725960
TI  - Contrasting alterations to synaptic and intrinsic properties in upper-cervical
      superficial dorsal horn neurons following acute neck muscle inflammation.
AB  - BACKGROUND: Acute and chronic pain in axial structures, like the back and neck,
      are difficult to treat, and have incidence as high as 15%. Surprisingly, most
      preclinical work on pain mechanisms focuses on cutaneous structures in the limbs
      and animal models of axial pain are not widely available. Accordingly, we
      developed a mouse model of acute cervical muscle inflammation and assessed the
      functional properties of superficial dorsal horn (SDH) neurons. RESULTS: Male
      C57/Bl6 mice (P24-P40) were deeply anaesthetised (urethane 2.2 g/kg i.p) and the
      rectus capitis major muscle (RCM) injected with 40 MUl of 2% carrageenan. Sham
      animals received vehicle injection and controls remained anaesthetised for 2 hrs.
      Mice in each group were sacrificed at 2 hrs for analysis. c-Fos staining was used
      to determine the location of activated neurons. c-Fos labelling in carrageenan
      injected mice was concentrated within ipsilateral (87% and 63% of labelled
      neurons in C1 and C2 segments, respectively) and contralateral laminae I - II
      with some expression in lateral lamina V. c-Fos expression remained below
      detectable levels in control and sham animals. In additional experiments, whole
      cell recordings were obtained from visualised SDH neurons in transverse slices in
      the ipsilateral C1 and C2 spinal segments. Resting membrane potential and input
      resistance were not altered. Mean spontaneous EPSC amplitude was reduced by ~20%
      in neurons from carrageenan-injected mice versus control and sham animals (20.63
      +/- 1.05 vs. 24.64 +/- 0.91 and 25.87 +/- 1.32 pA, respectively). The amplitude
      (238 +/- 33 vs. 494 +/- 96 and 593 +/- 167 pA) and inactivation time constant
      (12.9 +/- 1.5 vs. 22.1 +/- 3.6 and 15.3 +/- 1.4 ms) of the rapid A type potassium
      current (IAr), the dominant subthreshold current in SDH neurons, were reduced in
      carrageenan-injected mice. CONCLUSIONS: Excitatory synaptic drive onto, and
      important intrinsic properties (i.e., IAr) within SDH neurons are reduced two
      hours after acute muscle inflammation. We propose this time point represents an
      important transition period between peripheral and central sensitisation with
      reduced excitatory drive providing an initial neuroprotective mechanism during
      the early stages of the progression towards central sensitisation.

PMID- 24725961
TI  - Indicators for tracking programmes to strengthen health research capacity in
      lower- and middle-income countries: a qualitative synthesis.
AB  - BACKGROUND: The monitoring and evaluation of health research capacity
      strengthening (health RCS) commonly involves documenting activities and outputs
      using indicators or metrics. We sought to catalogue the types of indicators being
      used to evaluate health RCS and to assess potential gaps in quality and coverage.
      METHODS: We purposively selected twelve evaluations to maximize diversity in
      health RCS, funders, countries, and approaches to evaluation. We explored the
      quality of the indicators and extracted them into a matrix across individual,
      institutional, and national/regional/network levels, based on a matrix in the
      ESSENCE Planning, Monitoring and Evaluation framework. We synthesized across
      potential impact pathways (activities to outputs to outcomes) and iteratively
      checked our findings with key health RCS evaluation stakeholders. RESULTS:
      Evaluations varied remarkably in the strengths of their evaluation designs. The
      validity of indicators and potential biases were documented in a minority of
      reports. Indicators were primarily of activities, outputs, or outcomes, with
      little on their inter-relationships. Individual level indicators tended to be
      more quantitative, comparable, and attentive to equity considerations.
      Institutional and national-international level indicators were extremely diverse.
      Although linkage of activities through outputs to outcomes within evaluations was
      limited, across the evaluations we were able to construct potential pathways of
      change and assemble corresponding indicators. CONCLUSIONS: Opportunities for
      improving health RCS evaluations include work on indicator measurement properties
      and development of indicators which better encompass relationships with knowledge
      users. Greater attention to evaluation design, prospective indicator measurement,
      and systematic linkage of indicators in keeping with theories of change could
      provide more robust evidence on outcomes of health RCS.

PMID- 24725962
TI  - Effects of increasing organic loading rate on performance and microbial community
      shift of an up-flow anaerobic sludge blanket reactor treating diluted
      pharmaceutical wastewater.
AB  - The performance of an up-flow anaerobic sludge blanket (UASB) reactor was
      investigated in the treatment of diluted pharmaceutical fermentation wastewater
      for a continuous operation of 140 days. The dynamics and compositions of the
      microbial community were monitored using polymerase chain reaction (PCR)
      restriction fragment length polymorphism (PCR-RFLP) analysis. Increase of the
      organic loading rate (OLR) from 2.7 kg COD/m(3) d to 7.2 COD/m(3) d led to an
      increase in the COD removal efficiency from 83% to 91%. The dominant bacteria
      shifted from Proteobacteria (23.8%), Chloroflexi (14.5%) and Firmicutes (4.0%) to
      Firmicutes (48.4%), Bacteroidetes (9.5%) and Proteobacteria (5.4%). For archeaon,
      the dominant groups changed from Thermoplasmata (24.4%), Thermoprotei (18.0%) and
      Methanobacteria (30.8%) to Thermoplasmata (70.4%) and Methanomicrobia (16.8%).
      Firmicutes, Bacteroidetes, Thermoplasmata and Methanobacteria could outcompete
      other species and dominated in the reactor under higher OLR. The results
      indicated that, to some extent, microbial community shift could reflect the
      performance of the reactor and a significant community shift corresponded to a
      considerable process event.

PMID- 24725963
TI  - Abundance, transcription levels and phylogeny of bacteria capable of nitrous
      oxide reduction in a municipal wastewater treatment plant.
AB  - Nitrous oxide (N2O) production and expression of genes capable of its reduction
      were investigated in two full-scale parallel plug-flow activated sludge systems.
      These two systems continuously received wastewater with the same constituents,
      but operated under distinct nitrification efficiencies due to mixed liquor
      suspended solid (MLSS) concentration and the different hydraulic retention times
      (HRTs). A shorter HRT in system 2 resulted in a lower nitrification efficiency
      (40-60%) in conjunction with a high N2O emission (50.6 mg-N/L/day), whereas there
      was a higher nitrification efficiency (>99%) in system 1 with low N2O emission
      (22.6 mg-N/L/day). The DNA abundance of functional genes responsible for
      nitrification and denitrification were comparable in both systems, but
      transcription of nosZ mRNA in the lower N2O emission system (system 1) was one
      order of magnitude higher than that in the higher N2O emission system (system 2).
      The diversity and evenness of the nosZ gene were nearly identical; however, the
      predominant N2O reducing bacteria were phylogenetically distinct. Phylogenetic
      analysis indicated that N2O-reducing strains only retrieved in system 1 were
      close to the genera Rhodobacter, Oligotropha and Shinella, whereas they were
      close to the genera Mesorhizobium only in system 2. The distinct predominant N2O
      reducers may directly or indirectly influence N2O emissions.

PMID- 24725964
TI  - Importance of glucose-6-phosphate dehydrogenase (G6PDH) for vanillin tolerance in
      Saccharomyces cerevisiae.
AB  - Vanillin is derived from lignocellulosic biomass and, as one of the major biomass
      conversion inhibitors, inhibits yeast growth and fermentation. Vanillin was
      recently shown to induce the mitochondrial fragmentation and formation of mRNP
      granules such as processing bodies and stress granules in Saccharomyces
      cerevisiae. Furfural, another major biomass conversion inhibitor, also induces
      oxidative stress and is reduced in an NAD(P)H-dependent manner to its less toxic
      alcohol derivative. Therefore, the pentose phosphate pathway (PPP), through which
      most NADPH is generated, plays a role in tolerance to furfural. Although vanillin
      also induces oxidative stress and is reduced to vanillyl alcohol in a NADPH
      dependent manner, the relationship between vanillin and PPP has not yet been
      investigated. In the present study, we examined the importance of glucose-6
      phosphate dehydrogenase (G6PDH), which catalyzes the rate-limiting NADPH
      producing step in PPP, for yeast tolerance to vanillin. The growth of the null
      mutant of G6PDH gene (zwf1Delta) was delayed in the presence of vanillin, and
      vanillin was efficiently reduced in the culture of wild-type cells but not in the
      culture of zwf1Delta cells. Furthermore, zwf1Delta cells easily induced the
      activation of Yap1, an oxidative stress responsive transcription factor,
      mitochondrial fragmentation, and P-body formation with the vanillin treatment,
      which indicated that zwf1Delta cells were more susceptible to vanillin than wild
      type cells. These findings suggest the importance of G6PDH and PPP in the
      response of yeast to vanillin.

PMID- 24725965
TI  - Luminal (Her2 negative) prognostic index and survival of breast cancer patients.
AB  - PURPOSE: The group of luminal (Her2 negative) is distinguished from other
      subtypes of breast cancer. We aimed to produce a prognostic index specific for
      luminal (Her2 negative) subtype breast cancer that could assist clinical
      treatment. METHODS: The test set comprised 406 consecutive luminal (Her2
      negative) breast cancer patients. The relationship of 11 clinicopathologic
      factors including survivin with the 5-year disease-free survival was analyzed.
      RESULTS: In univariate analysis, TNM stage, surgery, tumor size, lymph node
      involvement, and survivin expression were prognostic factors. In multivariate
      analysis, tumor size [HR (95% CI): 1.98 (1.12-3.49), p=0.019], the number of
      lymph node metastasis [HR (95% CI): 1.75 (1.33-2.29), p<0.0001] and the
      expression of progesterone receptor [HR (95% CI): 0.58 (0.36-0.95), p=0.029] can
      independently predict prognosis. Prognostic index (PI) was calculated as
      0.68*tumor size+0.56*the number of lymph node metastasis-0.54*PR. According to
      the PI, patients were categorized into three groups: low, middle, and high risk
      group with the 5-year disease-free survival rates of 91.91%, 84.97% and 70.47%,
      respectively (P<0.001). In the validation set, the luminal prognostic index (LPI)
      remained significant. CONCLUSION: The LPI may be a useful tool for evaluating the
      outcome of patients with luminal (Her-2 negative) breast cancer.

PMID- 24725966
TI  - Role of calcifying nanoparticle in the development of hyperplasia and vascular
      calcification in an animal model.
AB  - OBJECTIVE: Calcifying nanoparticles (NPs) have been detected recently in
      calcified human arterial specimens and are involved in the process of
      calcification. This study was designed to test the hypothesis that human-derived
      NPs could worsen the response to arterial endothelial injury and induce vascular
      calcification. METHODS: The right carotid artery of 24 New Zealand rabbits was
      injured with an angioplasty balloon. Animals were perfused intravenously with
      saline (100 mL) during the experiment and divided into three groups: group-A,
      control; group-B, exposed to NPs (2 mL) obtained from calcified aortic valves;
      and group-C, exposed to NPs (2 mL) and treated postoperatively with atorvastatin
      (2.5 mg/kg/24 h). At 30 days, both carotid arteries were removed and examined
      histologically. Blood measurements were monitored during the study. RESULTS: The
      intimal hyperplasia area was significantly larger in the injured right carotid
      artery compared with the left unoperated carotid artery in all groups. There was
      no significant variation in medial area between groups. Morphometrically, the
      intima/media ratio (IMR) was significantly higher in damaged carotids compared
      with controls. A significant increase of IMR was found in group-B (1.81 +/- 0.41)
      compared with group-A (0.38 +/- 0.59; p = .004) or group-C (0.89 +/- 0.79; p =
      .035). Differences between groups C and A were not significant (p = .064).
      Calcifications were observed in six animals, all of which had been exposed to NPs
      (4 in group-B, 2 in group-C, p = .027). Plasma levels of cholesterol and
      triglycerides remained stable. CONCLUSIONS: This research confirms the ability of
      systemic inoculation of human-derived NPs to accelerate hyperplasia and stimulate
      calcification in localized areas of arteries previously submitted to endothelial
      damage, while it was harmless in healthy arteries. Atorvastatin was demonstrated
      to slow down this process.

PMID- 24725967
TI  - Molecular classifiers for acute kidney transplant rejection in peripheral blood
      by whole genome gene expression profiling.
AB  - There are no minimally invasive diagnostic metrics for acute kidney transplant
      rejection (AR), especially in the setting of the common confounding diagnosis,
      acute dysfunction with no rejection (ADNR). Thus, though kidney transplant
      biopsies remain the gold standard, they are invasive, have substantial risks,
      sampling error issues and significant costs and are not suitable for serial
      monitoring. Global gene expression profiles of 148 peripheral blood samples from
      transplant patients with excellent function and normal histology (TX; n = 46), AR
      (n = 63) and ADNR (n = 39), from two independent cohorts were analyzed with DNA
      microarrays. We applied a new normalization tool, frozen robust multi-array
      analysis, particularly suitable for clinical diagnostics, multiple prediction
      tools to discover, refine and validate robust molecular classifiers and we tested
      a novel one-by-one analysis strategy to model the real clinical application of
      this test. Multiple three-way classifier tools identified 200 highest value
      probesets with sensitivity, specificity, positive predictive value, negative
      predictive value and area under the curve for the validation cohort ranging from
      82% to 100%, 76% to 95%, 76% to 95%, 79% to 100%, 84% to 100% and 0.817 to 0.968,
      respectively. We conclude that peripheral blood gene expression profiling can be
      used as a minimally invasive tool to accurately reveal TX, AR and ADNR in the
      setting of acute kidney transplant dysfunction.

PMID- 24725968
TI  - Assessment of seasonality of influenza in swine using field submissions to a
      diagnostic laboratory in Ontario between 2007 and 2012.
AB  - BACKGROUND: Seasonality of any infectious disease is important for its control
      and monitoring. While influenza seasonality in people has been evaluated
      extensively, this question has not been studied well in swine populations.
      OBJECTIVE: The goal of this study was to investigate seasonality of influenza in
      swine, using diagnostic submissions to a diagnostic laboratory. METHODS: Two
      thousand seven hundred and eleven virological tests within 685 submissions and
      5471 serological tests within 193 submissions in Ontario swine between 2007 and
      2012 were included in the study and converted to total monthly number of
      virological and serological submissions, and the number of positive submissions.
      Data were analyzed by time-series decomposition, fixed-effect Poisson, random
      effect Poisson regression with month as uncorrelated and correlated random
      effects. RESULTS: All approaches identified seasonality in virological
      submissions (P < 0.02) with peak in January and April, and a trough in July, but
      were not able to detect seasonality of influenza-positive virological submissions
      (P > 0.13). Seasonality of positive serological submissions was identified only
      if independence between months was assumed (P < 0.03). Almost 50% of serological
      submissions had evidence of exposure to H3N2 and H1N1. CONCLUSIONS: Thus, this
      study identified evidence of seasonality in influenza-like disease in swine
      herds, but not in circulation of influenza virus. Evidence of seasonality in
      exposure to influenza was dependent on assumptions of between-month correlation.
      High exposure to H3N2 and H1N1 subtypes warrants more detailed investigation of
      within-herd influenza virus circulation. The study provides initial insight into
      seasonality of influenza in swine and should be followed with herd-level studies.

PMID- 24725969
TI  - Hybridizing Daphnia communities from ten neighbouring lakes: spatio-temporal
      dynamics, local processes, gene flow and invasiveness.
AB  - BACKGROUND: In natural communities of cyclical parthenogens, rapid response to
      environmental change is enabled by switching between two reproduction modes.
      While long periods of asexual reproduction allow some clones to outcompete
      others, and may result in "clonal erosion", sexual reproduction restores genetic
      variation in such systems. Moreover, sexual reproduction may result in the
      formation of interspecific hybrids. These hybrids can then reach high abundances,
      through asexual clonal reproduction. In the present study, we explored genetic
      variation in water fleas of the genus Daphnia. The focus was on the short-term
      dynamics within several clonal assemblages from the hybridizing Daphnia
      longispina complex and the impact of gene flow at small spatial scales. RESULTS:
      Daphnia individuals belonged either to the parental species D. galeata and D.
      longispina, or to different hybrid classes, as identified by 15 microsatellite
      markers. The distribution and genotypic structure of parental species, but not
      hybrids, corresponded well with the geographical positions of the lakes. Within
      parental species, the genetic distance among populations of D. galeata was lower
      than among populations of D. longispina. Moreover, D. galeata dominance was
      associated with higher phosphorous load. Finally, there was no evidence for
      clonal erosion. CONCLUSIONS: Our results suggest that the contemporary structure
      of hybridizing Daphnia communities from ten nearby lakes is influenced by
      colonization events from neighbouring habitats as well as by environmental
      factors. Unlike the parental species, however, there was little evidence for
      successful dispersal of hybrids, which seem to be produced locally. Finally, in
      contrast to temporary Daphnia populations, in which a decrease in clonal
      diversity was sometimes detectable over a single growing season, the high clonal
      diversity and lack of clonal erosion observed here might result from repeated
      hatching of sexually produced offspring. Overall, our study provides insights
      into spatio-temporal dynamics in a hybridizing Daphnia species complex in a
      recently established lake system, and relates genetic similarities of populations
      to a scenario of secondary invasion enhanced by environmental factors.

PMID- 24725972
TI  - Psychiatric symptoms in a patient with isolated adrenocorticotropin deficiency:
      case report and literature review.
AB  - We report a 59-year-old man with isolated adrenocorticotropin (ACTH) deficiency.
      The patient presented with sudden onset of delusions and hallucinations at the
      age of 54, which resolved gradually without treatment. Subsequently, the patient
      manifested stereotypy, wandering, hypobulia, and autistic symptoms, and was
      treated with antipsychotics for 1 year without any improvement. He suffered from
      neuroleptic malignant syndrome-like symptoms at the age of 59. A thorough
      endocrine assessment revealed isolated ACTH deficiency. After hydrocortisone
      supplementation, the physical and psychiatric symptoms improved dramatically.
      Clinicians should consider this rare disease when diagnosing patients with
      refractory psychiatric symptoms and unique physical symptoms of isolated ACTH
      deficiency.

PMID- 24725970
TI  - Cell-type specific expression of p11 controls cocaine reward.
AB  - BACKGROUND: The high rate of comorbidity between depression and cocaine addiction
      suggests shared molecular mechanisms and anatomical pathways. Limbic structures,
      such as the nucleus accumbens (NAc), play a crucial role in both disorders, yet
      how different cell types within these structures contribute to the pathogenesis
      remains elusive. Downregulation of p11 (S100A10), specifically in the NAc,
      elicits depressive-like behaviors in mice, but its role in drug addiction is
      unknown. METHODS: We combined mouse genetics and viral strategies to determine
      how the titration of p11 levels within the entire NAc affects the rewarding
      actions of cocaine on behavior (six to eight mice per group) and molecular
      correlates (three experiments, five to eight mice per group). Finally, the
      manipulation of p11 expression in distinct NAc dopaminoceptive neuronal subsets
      distinguished cell-type specific effects of p11 on cocaine reward (five to eight
      mice per group). RESULTS: We demonstrated that p11 knockout mice have enhanced
      cocaine conditioned place preference, which is reproduced by the focal
      downregulation of p11 in the NAc of wild-type mice. In wild-type mice, cocaine
      reduced p11 expression in the NAc, while p11 overexpression exclusively in the
      NAc reduced cocaine conditioned place preference. Finally, we identified dopamine
      receptor-1 expressing medium spiny neurons as key mediators of the effects of p11
      on cocaine reward. CONCLUSIONS: Our data provide evidence that disruption of p11
      homeostasis in the NAc, particularly in dopamine receptor-1 expressing medium
      spiny neurons, may underlie pathophysiological mechanisms of cocaine rewarding
      action. Treatments to counter maladaptation of p11 levels may provide novel
      therapeutic opportunities for cocaine addiction.

PMID- 24725971
TI  - Lower levels of trust in one's physician is associated with more distress over
      time in more anxiously attached individuals with cancer.
AB  - OBJECTIVE: In the present study, we investigated individual differences in the
      outcome of patient-physician trust when confronted with cancer from an attachment
      theoretical perspective. We expected that lower levels of trust are associated
      with more emotional distress and more physical limitations within the first 15
      months after diagnosis, especially in those who score relatively high on
      attachment anxiety. No such association was expected for more avoidantly attached
      individuals. METHOD: A group of 119 patients with different types of cancer
      (breast, cervical, intestinal and prostate) completed questionnaires concerning
      trust (short version of the Wake Forest Physician Trust Scale) and attachment
      (Experiences in Close Relationship scale Revised) at 3 months after diagnosis.
      Emotional distress (Hospital Anxiety and Depression Scale) and physical
      limitations (physical functioning subscales of the European Organization for
      Research and Treatment of Cancer, Quality of Life Questionnaire-C30) were
      assessed at 3, 9 and 15 months after diagnosis. To test the hypotheses, multiple
      hierarchical regression analyses were performed. RESULTS: Lower levels of trust
      were associated with more emotional distress and more physical limitations at 3,
      9 and 15 months after diagnosis in more anxiously attached patients, but not in
      less anxiously attached patients. DISCUSSION: These results indicate an
      attachment-dependent effect of trust in one's physician. Explanations and
      clinical implications are discussed.

PMID- 24725973
TI  - Correlates of hepatitis B among patients with mental illness in Brazil.
AB  - OBJECTIVE: To assess correlates of hepatitis B among adults with mental illness
      under care in Brazil. METHOD: Cross-sectional national multicenter study of 2206
      patients with mental illnesses randomly selected from 26 public mental health
      services. Sociodemographic and behavioral data were obtained from face-to-face
      interviews and psychiatric diagnoses from medical charts. Serology testing was
      conducted, and prevalence rate ratios were estimated by log-binomial regression.
      RESULTS: The weighted prevalence rates of current hepatitis B virus (HBV)
      infection (HBsAg+) and previous HBV exposure (anti-HBc+) were 2.0% [95%
      confidence interval (CI): 1.5%-2.7%] and 17.1% (95% CI: 16.0%-19.0%),
      respectively. Correlates of HBsAg+ included male gender, younger age (18-29
      years), unstable place of residence, intellectual disability, main psychiatric
      diagnosis of dementia, presence of other medical comorbitidy, use of
      alcohol/drugs during sex, more than one sexual partner and use of cocaine.
      Correlates of anti-HBc+ included male gender, older age (>=30 years), black skin
      color, lower education, unstable place of residence, currently hospitalized,
      intellectual disability, history of any sexually transmitted disease or syphilis,
      poor HIV knowledge, history of imprisonment and sexual violence. CONCLUSIONS:
      Hepatitis B is an important comorbidity among psychiatric patients in Brazil.
      Screening for HBV, effective prevention and intervention strategies, including
      universal HBV immunization, should be routine practices in these mental health
      services.

PMID- 24725974
TI  - Making progress: the role of cancer councils in Australia in indigenous cancer
      control.
AB  - BACKGROUND: Indigenous Australians have poorer outcomes from cancer for a variety
      of reasons including poorer participation in screening programs, later diagnosis,
      higher rates of cancer with poor prognosis and poorer uptake and completion of
      treatment. Cancer prevention and support for people with cancer is part of the
      core business of the State and Territory Cancer Councils. To support sharing of
      lessons learned, this paper reports an environmental scan undertaken in 2010 in
      cancer councils (CCs) nationwide that aimed to support Indigenous cancer control.
      METHODS: The methods replicated the approach used in a 2006 environmental scan of
      Indigenous related activity in CCs. The Chief Executive Officer of each CC
      nominated individuals for interview. Interviews explored staffing, projects,
      programs and activities to progress cancer control issues for Indigenous
      Australians, through phone or face-to-face interviews. Reported initiatives were
      tabulated using predetermined categories of activity and summaries were returned
      to interviewees, the Aboriginal and Torres Strait Islander Subcommittee and Chief
      Executive Officers for verification. RESULTS: All CCs participated and modest
      increases in activity had occurred in most states since 2006 through different
      means. Indigenous staff numbers were low and no Indigenous person had yet been
      employed in smaller CCs; no CC had an Indigenous Board member and efforts at
      capacity building were often directed outside of the organisation. Developing
      partnerships with Indigenous organisations were ongoing. Acknowledgement and
      specific mention of Indigenous people in policy was increasing. Momentum
      increased following the establishment of a national subcommittee which increased
      the profile of Indigenous issues and provided collegial and practical support for
      those committed to reducing Indigenous cancer disparities. Government funding of
      "Closing the Gap" and research in the larger CCs have been other avenues for
      increasing knowledge and activity in Indigenous cancer control. CONCLUSIONS: This
      environmental scan measured progress, allowed sharing of information and provided
      critical assessment of progress across areas of importance for increasing
      Indigenous cancer control. Structured examination of policies, institutional
      support systems, programs and interventions is a useful means of highlighting
      opportunities for progress with minority groups relevant for many organisations.
      Progress has occurred with momentum likely to increase in the future and benefit
      from commitment to long-term monitoring and sharing of achievements.

PMID- 24725976
TI  - Triterpenoid saponins from the roots of two Gypsophila species.
AB  - Two triterpenoid saponins with two known ones have been isolated from the roots
      of Gypsophila arrostii var. nebulosa, and two new ones from the roots of
      Gypsophila bicolor. Their structures were established by extensive NMR and mass
      spectroscopic techniques as 3-O-beta-d-galactopyranosyl-(1->2)-[beta-d
      xylopyranosyl-(1->3)]-beta-d-glucuronopyranosylquillaic acid 28-O-beta-d
      xylopyranosyl-(1->4)-[beta-d-glucopyranosyl-(1->3)]-alpha-l-rhamnopyranosyl-(1
      >2)-[beta-d-glucopyranosyl-(1->4)]-beta-d-fucopyranosyl ester (1), 3-O-beta-d
      galactopyranosyl-(1->2)-[beta-d-xylopyranosyl-(1->3)]-beta-d
      glucuronopyranosylgypsogenin 28-O-beta-d-xylopyranosyl-(1->4)-[beta-d
      glucopyranosyl-(1->3)]-alpha-l-rhamnopyranosyl-(1->2)-[beta-d-glucopyranosyl-(1
      >4)]-beta-d-fucopyranosyl ester (2), 3-O-beta-d-galactopyranosyl-(1->2)-[beta-d
      xylopyranosyl-(1->3)]-beta-d-glucuronopyranosylgypsogenin 28-O-beta-d
      xylopyranosyl-(1->3)-beta-d-xylopyranosyl-(1->4)-alpha-l-rhamnopyranosyl-(1->2)
      [(4-O-acetyl)-beta-d-quinovopyranosyl-(1->4)]-beta-d-fucopyranosyl ester (3),
      gypsogenic acid 28-O-beta-d-glucopyranosyl-(1->3)-{6-O-[3-hydroxy-3
      methylglutaryl]-beta-d-glucopyranosyl-(1->6)}-beta-d-galactopyranosyl ester (4).
      Three compounds were evaluated against one human colon cancer cell line SW480 and
      one rat cardiomyoblast cell line H9c2. 

PMID- 24725977
TI  - Chemical and genetic similarity and diversity of Ligularia anoleuca and L.
      fischeri collected in the Hengduan Mountains of China.
AB  - The sesquiterpenoid composition in the root and the DNA sequences of
      evolutionarily neutral regions were studied in Ligularia anoleuca and Ligularia
      fischeri (Asteraceae) collected in the Sichuan Province of China. LC-MS analysis
      showed that L. anoleuca populations from different localities had different
      chemical compositions. However, the isolated compounds were similar to each
      other, indicating that the differences in chemical composition were not large.
      The DNA analysis suggested that the two species were indistinguishable. Seventeen
      furanoeremophilanes and an eremophilane acetal were isolated. 

PMID- 24725975
TI  - Pyrosequencing for rapid detection of tuberculosis resistance in clinical
      isolates and sputum samples from re-treatment pulmonary tuberculosis patients.
AB  - BACKGROUND: Multidrug-resistant tuberculosis (MDR-TB) is a major public health
      problem. Early diagnosis of MDR-TB patients is essential for minimizing the risk
      of Mycobacterium tuberculosis (MTB) transmission. The conventional drug
      susceptibility testing (DST) methods for detection of drug-resistant M.
      tuberculosis are laborious and cannot provide the rapid detection for clinical
      practice. METHODS: The aim of this study was to develop a pyrosequencing approach
      for the simultaneous detection of resistance to rifampin (RIF), isoniazid (INH),
      ethambutol (EMB), streptomycin (SM), ofloxacin (OFL) and amikacin (AMK) in M.
      tuberculosis clinical isolates and sputum samples from re-treatment pulmonary
      tuberculosis (PTB) patients. We identified the optimum conditions for detection
      mutation of rpoB, katG, rpsl, embB, gyrA and rrs gene by pyrosequencing. Then
      this approach was applied to detect 205 clinical isolates and 24 sputum samples
      of M. tuberculosis from re-treatment PTB patients. RESULTS: The mutations of rpoB
      and gyrA gene were detected by pyrosequencig with the SQA mode, and the mutations
      of katG, rpsl, embB, gyrA and rrs gene were detected by pyrosequencing with SNP
      mode. Compared with the Bactec MGIT 960 mycobacterial detection system, the
      accuracy of pyrosequencing for the detection of RIF, INH, EMB, SM, AMK and OFL
      resistance in clinical isolates was 95.0%, 79.2%, 70.3%, 84.5%, 96.5% and 91.1%,
      respectively. In sputum samples the accuracy was 83.3%, 83.3%, 60.9%, 83.3%,
      87.5% and 91.7%, respectively. CONCLUSIONS: The newly established pyrosequencing
      assay is a rapid and high-throughput method for the detection of resistance to
      RIF, INH, SM, EMB, OFL and AMK in M. tuberculosis. Pyrosequencing can be used as
      a practical molecular diagnostic tool for screening and predicting the resistance
      of re-treatment pulmonary tuberculosis patients.

PMID- 24725978
TI  - A domain swapping approach to elucidate differential regiospecific hydroxylation
      by geraniol and linalool synthases from perilla.
AB  - Geraniol and linalool are acyclic monoterpenes found in plant essential oils that
      have attracted much attention for their commercial use and in pharmaceutical
      studies. They are synthesized from geranyl diphosphate (GDP) by geraniol and
      linalool synthases, respectively. Both synthases are very similar at the amino
      acid level and share the same substrate; however, the position of the GDP to
      which they introduce hydroxyl groups is different. In this study, the mechanisms
      underlying the regiospecific hydroxylation of geraniol and linalool synthases
      were investigated using a domain swapping approach and site-directed mutagenesis
      in perilla. Sequences of the synthases were divided into ten domains (domains I
      to IV-4), and each corresponding domain was exchanged between both enzymes. It
      was shown that different regions were important for the formation of geraniol and
      linalool, namely, domains IV-1 and -4 for geraniol, and domains III-b, III-d, and
      IV-4 for linalool. These results suggested that the conformation of carbocation
      intermediates and their electron localization were seemingly to be different
      between geraniol and linalool synthases. Further, five amino acids in domain IV-4
      were apparently indispensable for the formation of geraniol and linalool.
      According to three-dimensional structural models of the synthases, these five
      residues seemed to be responsible for the different spatial arrangement of the
      amino acid at H524 in the case of geraniol synthase, while N526 is the
      corresponding residue in linalool synthase. These results suggested that the side
      chains of these five amino acids, in combination with several relevant domains,
      localized the positive charge in the carbocation intermediate to determine the
      position of the introduced hydroxyl group. 

PMID- 24725979
TI  - Plasma 25-hydroxyvitamin D and risk of premenstrual syndrome in a prospective
      cohort study.
AB  - BACKGROUND: Moderate to severe premenstrual syndrome (PMS) affects 8-20 percent
      of premenopausal women. Previous studies suggest that high dietary vitamin D
      intake may reduce risk. However, vitamin D status is influenced by both dietary
      vitamin D intake and sunlight exposure and the association of vitamin D status
      with PMS remains unclear. METHODS: We assessed the relation of plasma 25
      hydroxyvitamin D (25OHD), total calcium and parathyroid hormone levels with risk
      of PMS and specific menstrual symptoms in a case-control study nested within the
      prospective Nurses' Health Study II. Cases were 401 women free from PMS at
      baseline who developed PMS during follow-up (1991-2005). Controls were women not
      experiencing PMS (1991-2005), matched 1:1 with cases on age and other factors.
      Timed luteal phase blood samples were collected between 1996 and 1999 from cases
      and controls. We used conditional logistic regression to model the relation of
      25OHD levels with risk of PMS and individual menstrual symptoms. RESULTS: In
      analyses of all cases and controls, 25OHD levels were not associated with risk of
      PMS. However, results differed when the timing of blood collection vs. PMS
      diagnosis was considered. Among cases who had already been diagnosed with PMS at
      the time of blood collection (n = 279), 25OHD levels were positively associated
      with PMS, with each 10 nmol/L change in 25OHD associated with a 13% higher risk.
      Among cases who developed PMS after blood collection (n = 123), 25OHD levels were
      unrelated to risk of PMS overall, but inversely related to risk of specific
      menstrual symptoms. For example, each 10 nmol/L increase was associated with a
      significant 21% lower risk of breast tenderness (P = 0.02). Total calcium or
      parathyroid hormone levels were unrelated to PMS. CONCLUSIONS: 25OHD levels were
      not associated with overall risk of PMS. The positive association observed among
      women already experiencing PMS at the time of 25OHD measurement is likely due to
      confounding by indication related to use of dietary supplements to treat
      menstrual symptoms. Results from prospective analyses, which were less likely
      influenced by this bias, suggest that higher 25OHD levels may be inversely
      related to the development of specific menstrual symptoms.

PMID- 24725980
TI  - Canadian Society of Nephrology commentary on the 2012 KDIGO clinical practice
      guideline for the management of blood pressure in CKD.
AB  - The KDIGO (Kidney Disease: Improving Global Outcomes) 2012 clinical practice
      guideline for the management of blood pressure (BP) in chronic kidney disease
      (CKD) provides the structural and evidence base for the Canadian Society of
      Nephrology (CSN) commentary on this guideline's relevancy and application to the
      Canadian health care system. While in general agreement, we provide commentary on
      13 of the 21 KDIGO guideline statements. Specifically, we agreed that
      nonpharmacological interventions should play a significant role in the management
      of hypertension in patients with CKD. We also agreed that the approach to the
      management of hypertension in elderly patients with CKD should be individualized
      and take into account comorbid conditions to avoid adverse outcomes from
      excessive BP lowering. In contrast to KDIGO, the CSN Work Group believes there is
      insufficient evidence to target a lower BP for nondiabetic CKD patients based on
      the presence and severity of albuminuria. The CSN Work Group concurs with the
      Canadian Hypertension Education Program (CHEP) recommendation of a target BP for
      all non-dialysis-dependent CKD patients without diabetes of <=140 mm Hg systolic
      and <=90 mm Hg diastolic. Similarly, it is our position that in diabetic patients
      with CKD and normal urinary albumin excretion, raising the threshold for
      treatment from <130 mm Hg systolic BP to <140 mm Hg systolic BP could increase
      stroke risk and the risk of worsening kidney disease. The CSN Work Group concurs
      with the CHEP and the Canadian Diabetic Association recommendation for diabetic
      patients with CKD with or without albuminuria to continue to be treated to a BP
      target similar to that of the overall diabetes population, aiming for BP levels <
      130/80 mm Hg. Consistent with this, the CSN Work Group endorses a BP target of
      <130/80 mm Hg for diabetic patients with a kidney transplant. Finally, in the
      absence of evidence for a lower BP target, the CSN Work Group concurs with the
      CHEP recommendation to target BP<140/90 mm Hg for nondiabetic patients with a
      kidney transplant.

PMID- 24725981
TI  - Loin pain hematuria syndrome.
AB  - Loin pain hematuria syndrome is a rare disease with a prevalence of ~0.012%. The
      most prominent clinical features include periods of severe intermittent or
      persistent unilateral or bilateral loin pain accompanied by either microscopic or
      gross hematuria. Patients with loin pain hematuria syndrome initially present
      with hematuria, flank pain, or most often both hematuria and flank pain. Kidney
      biopsies from patients with loin pain hematuria typically reveal only minor
      pathologic abnormalities. Further, loin pain hematuria syndrome is not associated
      with loss of kidney function or urinary tract infections. Loin pain hematuria
      syndrome-associated hematuria and pain are postulated to be linked to vascular
      disease of the kidney, coagulopathy, renal vasospasm with microinfarction,
      hypersensitivity, complement activation on arterioles, venocalyceal fistula,
      abnormal ureteral peristalsis, and intratubular deposition of calcium or uric
      acid microcrystals. Many patients with loin pain hematuria syndrome also meet
      criteria for a somatoform disorder, and analgesic medications, including
      narcotics, commonly are used to treat loin pain hematuria syndrome-associated
      pain. Interventional treatments include renal denervation, kidney
      autotransplantation, and nephrectomy; however, these methods should be used only
      as a last resort when less invasive measures have been tried unsuccessfully. In
      this review article, we discuss and critique current clinical practices related
      to loin pain hematuria syndrome pathophysiology, diagnosis, treatment, and
      prognosis. 

PMID- 24725982
TI  - Health Care Workers' Knowledge and Confidence in Personal Protective Equipment
      During the H1N1 Pandemic in Israel.
AB  - OBJECTIVES: Healthcare workers (HCW) are at increased risk of infection during
      pandemics. HCW personal protective equipment (PPE) use has been shown to lower
      infection rates among HCW and patients. However, low compliance and misuse are
      frequent. Since future outbreaks are unavoidable, this issue needs to be
      addressed. METHODS: A validated questionnaire was distributed to 617 HCWs (nurses
      and physicians) in 21 hospitals and 40 primary care clinics in Israel at the peak
      of the A/H1N1 pandemic. RESULTS: PPE confidence was higher among HCWs with higher
      tested and self-perceived knowledge. Confidence was also higher among nurses
      compared with physicians and among employees in hospitals compared with those in
      primary care clinics. Experience treating A/H1N1 patients was related to higher
      self-perceived knowledge and PPE confidence. CONCLUSIONS: High levels of PPE
      knowledge were significantly correlated to HCWs' confidence in PPE and may help
      increase PPE usage and reduce absenteeism. (Diaster Med Public Health
      Preparedness. 2014;0:1-8).

PMID- 24725985
TI  - The effect of notchplasty on tunnel widening in anterior cruciate ligament
      reconstruction.
AB  - PURPOSE: To investigate changes in femoral tunnel diameter, dimension, and volume
      after anterior cruciate ligament reconstruction with notchplasty. METHODS:
      Porcine knee specimens were divided into 2 groups of 10 specimens each. Group A
      did not receive notchplasty. A 2-mm notchplasty was conducted in group B. Seven
      millimeter-diameter femoral tunnels were drilled and a doubled flexor digitorum
      profundus tendon was inserted and fixed with an EndoButton (Smith & Nephew,
      Andover, MA) in each knee specimen. Samples were mounted on a materials testing
      machine. Each group was preloaded at 10 N and subjected to 20 loading cycles
      (between 0 and 40 N), followed by 1,000 loading cycles in the elastic region
      (between 10 and 150 N). High-resolution computed tomography with 1.0-mm slices
      was conducted with all samples before and after testing. A 3-dimensional model
      was constructed to evaluate the degree of the tunnel change. RESULTS: In group B
      the mean longest diameter and dimension of the femoral tunnel significantly
      increased after the test (P = .005 and P = .001, respectively). The volumetric
      loss of bony structure after the test in group B was significantly greater than
      that in group A (P = .039). Meanwhile, no significant difference was found before
      and after the test in terms of tunnel diameter, dimension, and volumetric loss
      around the tunnel in group A. CONCLUSIONS: The intra-articular orifice of the
      femoral tunnel was enlarged after the uniaxial cyclic loading test after
      notchplasty. An enlarged tunnel orifice may lead to a discrepancy between the
      tunnel and the graft at the tunnel aperture. CLINICAL RELEVANCE: The data may
      have an implication that suspensory fixation with a notchplasty has a negative
      effect on the full graft accommodation at the tunnel aperture. Aperture widening
      may affect graft positioning, leading to subtle changes in graft biomechanics and
      laxity.

PMID- 24725986
TI  - Foot and ankle tendoscopy: evidence-based recommendations.
AB  - PURPOSE: The purpose of this study was to provide a comprehensive review of the
      current literature on tendoscopy of the foot and ankle and assign an evidence
      based grade of recommendation for or against intervention. METHODS: A
      comprehensive review of the literature was performed on May 26, 2013, using the
      PubMed, Cochrane, and Scopus databases. Studies focusing on the use of foot and
      ankle tendoscopy were isolated, and these articles were then reviewed and
      assigned a Level of Evidence (I through V). The literature was then analyzed, and
      a grade of recommendation was assigned for tendoscopy of the tendons of the foot
      and ankle on which the procedure is generally performed. RESULTS: There is weak
      evidence (grade Cf) to support the use of tendoscopy on the Achilles, flexor
      hallucis longus, and peroneal tendons. Insufficient evidence (grade I) exists to
      assign a grade of recommendation for tendoscopy of the tibialis posterior,
      tibialis anterior, flexor digitorum longus, extensor hallucis longus, and
      extensor digitorum longus. CONCLUSIONS: A comprehensive review of the literature
      on foot and ankle tendoscopy has shown predominantly Level IV and V studies, with
      just 1 Level II study. On the basis of the current literature available, there is
      poor evidence (grade Cf) in support of Achilles, flexor hallucis longus, and
      peroneal tendoscopy for the common indications. There is insufficient evidence to
      make a recommendation (grade I) for or against tendoscopy of the tibialis
      posterior, tibialis anterior, flexor digitorum longus, extensor hallucis longus,
      and extensor digitorum longus. Although current literature suggests that
      tendoscopy is a safe and effective procedure, original scientific articles of
      higher levels of evidence are needed before a stronger recommendation can be
      assigned. LEVEL OF EVIDENCE: Level IV, systematic review of Level II, IV, and V
      studies.

PMID- 24725987
TI  - Platelet-derived growth factor regulates the secretion of extracellular vesicles
      by adipose mesenchymal stem cells and enhances their angiogenic potential.
AB  - BACKGROUND: Several studies demonstrate the role of adipose mesenchymal stem
      cells (ASCs) in angiogenesis. The angiogenic mechanism has been ascribed to
      paracrine factors since these cells secrete a plenty of signal molecules and
      growth factors. Recently it has been suggested that besides soluble factors,
      extracellular vesicles (EVs) that include exosomes and microvesicles may play a
      major role in cell-to-cell communication. It has been shown that EVs are
      implicated in the angiogenic process. RESULTS: Herein we studied whether EVs
      released by ASCs may mediate the angiogenic activity of these cells. Our results
      demonstrated that ASC-derived EVs induced in vitro vessel-like structure
      formation by human microvascular endothelial cells (HMEC). EV-stimulated HMEC
      when injected subcutaneously within Matrigel in SCID mice formed vessels.
      Treatment of ASCs with platelet-derived growth factor (PDGF) stimulated the
      secretion of EVs, changed their protein composition and enhanced the angiogenic
      potential. At variance of EVs released in basal conditions, PDGF-EVs carried c
      kit and SCF that played a role in angiogenesis as specific blocking antibodies
      inhibited in vitro vessel-like structure formation. The enhanced content of
      matrix metalloproteinases in PDGF-EVs may also account for their angiogenic
      activity. CONCLUSIONS: Our findings indicate that EVs released by ASCs may
      contribute to the ASC-induced angiogenesis and suggest that PDGF may trigger the
      release of EVs with an enhanced angiogenic potential.

PMID- 24725988
TI  - Sacred psychiatry in ancient Greece.
AB  - From the ancient times, there are three basic approaches for the interpretation
      of the different psychic phenomena: the organic, the psychological, and the
      sacred approach. The sacred approach forms the primordial foundation for any
      psychopathological development, innate to the prelogical human mind. Until the
      second millennium B.C., the Great Mother ruled the Universe and shamans cured the
      different mental disorders. But, around 1500 B.C., the predominance of the
      Hellenic civilization over the Pelasgic brought great changes in the theological
      and psychopathological fields. The Hellenes eliminated the cult of the Great
      Mother and worshiped Dias, a male deity, the father of gods and humans. With the
      Father's help and divinatory powers, the warrior-hero made diagnoses and found
      the right therapies for mental illness; in this way, sacerdotal psychiatry was
      born. 

PMID- 24725989
TI  - Recurrent aphthous stomatitis and pain management with low-level laser therapy: a
      randomized controlled trial.
AB  - OBJECTIVE: The aim of the study was to determine whether low-level laser therapy
      (LLLT) has an analgesic effect in patients with recurrent aphthous stomatitis
      (RAS). STUDY DESIGN: A randomized single-blinded placebo-controlled trial was
      conducted with LLLT (wavelength, 809 nm; power, 60 mW; pulse frequency, 1800 Hz;
      duration, 80 seconds per treatment; dose, 6.3 J/cm(2)) in 40 patients with RAS.
      The intervention group was treated with LLLT on 3 occasions, with a 1-day
      interval. The control group was treated similarly, without any laser power. Pain
      perception (visual analog scale [VAS] rating) and patients' experience of eating,
      drinking, and brushing teeth was registered. RESULTS: VAS rating decreased (day 0
      until day 2) from 84.7 to 31.5 (LLLT) and from 81.7 to 76.1 (placebo) (P <
      .0001). LLLT also relieved the difficulty of drinking, eating, and brushing
      teeth. CONCLUSIONS: LLLT reduced the pain and the inconvenience of eating,
      drinking, and brushing teeth for patients with RAS, compared with placebo.

PMID- 24725990
TI  - Relationship between appearance of tongue carcinoma on intraoral ultrasonography
      and histopathologic findings.
AB  - OBJECTIVE: To clarify whether intraoral ultrasonography (I-US) is effective for
      predicting metastasis of tongue cancer to the cervical lymph nodes. STUDY DESIGN:
      Participants comprised 29 patients with tongue carcinoma classified as T1-T4
      using the TNM staging system. All patients underwent I-US preoperatively.
      Postoperatively, resected specimens were evaluated histopathologically. RESULTS:
      I-US found that cases with invasive depth >=3 mm had higher potential for
      cervical lymph node metastasis than those with invasive depth <3 mm (P < .05). No
      other significant relationships were identified between observations on I-US and
      cervical lymph node metastasis. Cases with histopathologic blood vessel
      infiltration or lymph duct infiltration had a significant difference in risk of
      cervical lymph node metastasis. CONCLUSIONS: I-US is useful for preoperatively
      assessing the invasive depth of tongue carcinoma. Furthermore, observations from
      I-US and invasive depth of the tumor allowed presumptive diagnosis with regard to
      cervical lymph node metastasis.

PMID- 24725991
TI  - Relationships between third-molar juxta-apical radiolucencies and mandibular
      canals in panoramic and cone beam computed tomography images.
AB  - OBJECTIVE: This study aimed to determine the relationship between third-molar
      juxta-apical radiolucencies and mandibular canals on panoramic and cone beam
      computed tomography (CBCT) images. STUDY DESIGN: Forty-two patients were included
      in this retrospective study. The root apices and the relationships of the juxta
      apical radiolucencies to the mandibular canals were evaluated on both panoramic
      and CBCT images. The McNemar test (P < .05) was used to compare panoramic with
      CBCT findings. RESULTS: Root apices were visualized clearly with CBCT in most
      cases for which the apices were not seen clearly on panoramic images. Similarly,
      juxta-apical radiolucencies were separate from the mandibular canals with CBCT in
      most cases. CONCLUSIONS: The present study found that there is no consistent
      intimate relationship between juxta-apical radiolucencies and the mandibular
      canals. Similar studies with larger sample sizes are required to further confirm
      these findings.

PMID- 24725992
TI  - The effects of microRNAs on human neural stem cell differentiation in two- and
      three-dimensional cultures.
AB  - INTRODUCTION: Stem cells have the ability to self-renew or to differentiate into
      numerous cell types; however, our understanding of how to control and exploit
      this potential is currently limited. An emerging hypothesis is that microRNAs
      (miRNAs) play a central role in controlling stem cell-fate determination. Herein,
      we have characterized the effects of miRNAs in differentiated human neural stem
      cells (hNSCs) by using a cell line currently being tested in clinical trials for
      stroke disability (NCT01151124, Clinicaltrials.gov). METHODS: HNSCs were
      differentiated on 2- (2D) and 3-dimensional (3D) cultures for 1 and 3 weeks.
      Quantification of hNSC differentiation was measured with real-time PCR and axon
      outgrowth. The miRNA PCR arrays were implemented to investigate differential
      expression profiles in differentiated hNSCs. Evaluation of miRNA effects on hNSCs
      was performed by using transfection of miRNA mimics, real-time PCR, Western blot,
      and immunocytochemistry. RESULTS: The 3D substrate promoted enhanced hNSC
      differentiation coupled with a loss of cell proliferation. Differentiated hNSCs
      exhibited a similar miRNA profiling. However, in 3D samples, the degree and
      timing of regulation were significantly different in miRNA members of cluster mi
      R17 and miR-96-182, and hsa-miR-302a. Overall, hNSC 3D cultures demonstrated
      differential regulation of miRNAs involved in hNSC stemness, cell proliferation,
      and differentiation. The miRNA mimic analysis of hsa-miR-146b-5p and hsa-miR-99a
      confirmed induction of lineage-committed progenitors. Downregulated miRNAs were
      more abundant; those most significantly downregulated were selected, and their
      putative target mRNAs analyzed with the aim of unraveling their functionality. In
      differentiated hNSCs, downregulated hsa-miR-96 correlated with SOX5 upregulation
      of gene and protein expression; similar results were obtained for hsa-miR-302a,
      hsa-miR-182, hsa-miR-7, hsa-miR-20a/b, and hsa-miR-17 and their target NR4A3.
      Moreover, SOX5 was identified as a direct target gene of hsa-miR-96, and NR43A, a
      direct target of hsa-miR-7 and hsa-mir-17 by luciferase reporter assays.
      Therefore, the regulatory role of these miRNAs may occur through targeting NR4A3
      and SOX5, both reported as modulators of cell-cycle progression and axon length.
      CONCLUSIONS: The results provide new insight into the identification of specific
      miRNAs implicated in hNSC differentiation. These strategies may be exploited to
      optimize in vitro hNSC differentiation potential for use in preclinical studies
      and future clinical applications.

PMID- 24725993
TI  - A novel mutation in DDR2 causing spondylo-meta-epiphyseal dysplasia with short
      limbs and abnormal calcifications (SMED-SL) results in defective intra-cellular
      trafficking.
AB  - BACKGROUND: The rare autosomal genetic disorder, Spondylo-meta-epiphyseal
      dysplasia with short limbs and abnormal calcifications (SMED-SL), is reported to
      be caused by missense or splice site mutations in the human discoidin domain
      receptor 2 (DDR2) gene. Previously our group has established that trafficking
      defects and loss of ligand binding are the underlying cellular mechanisms of
      several SMED-SL causing mutations. Here we report the clinical characteristics of
      two siblings of consanguineous marriage with suspected SMED-SL and identification
      of a novel disease-causing mutation in the DDR2 gene. METHODS: Clinical
      evaluation and radiography were performed to evaluate the patients. All the
      coding exons and splice sites of the DDR2 gene were sequenced by Sanger
      sequencing. Subcellular localization of the mutated DDR2 protein was determined
      by confocal microscopy, deglycosylation assay and Western blotting. DDR2 activity
      was measured by collagen activation and Western analysis. RESULTS: In addition to
      the typical features of SMED-SL, one of the patients has an eye phenotype
      including visual impairment due to optic atrophy. DNA sequencing revealed a novel
      homozygous dinucleotide deletion mutation (c.2468_2469delCT) on exon 18 of the
      DDR2 gene in both patients. The mutation resulted in a frameshift leading to an
      amino acid change at position S823 and a predicted premature termination of
      translation (p.S823Cfs*2). Subcellular localization of the mutant protein was
      analyzed in mammalian cell lines, and it was found to be largely retained in the
      endoplasmic reticulum (ER), which was further supported by its N-glycosylation
      profile. In keeping with its cellular mis-localization, the mutant protein was
      found to be deficient in collagen-induced receptor activation, suggesting protein
      trafficking defects as the major cellular mechanism underlying the loss of DDR2
      function in our patients. CONCLUSIONS: Our results indicate that the novel
      mutation results in defective trafficking of the DDR2 protein leading to loss of
      function and disease. This confirms our previous findings that DDR2 missense
      mutations occurring at the kinase domain result in retention of the mutant
      protein in the ER.

PMID- 24725994
TI  - Longitudinal study of long-term smoking behaviour by biomarker-supported
      determination of exposure to smoke.
AB  - BACKGROUND: Long-term studies of smokers who switch to lower nicotine yield
      cigarettes have been identified by the World Health Organization Study Group
      TobReg and the US Food and Drug Administration as one key area where new
      knowledge is required to guide science based regulation. The limited number of
      long-term switching studies have concluded that smokers who switch to lower
      nicotine yield cigarettes show evidence of partial compensation. Since the
      European Union tobacco product directive of 2001 introduced tar and nicotine
      yield ceilings, there has been no long-term observational switching study. To
      address the limitations of previous studies where smokers were forced switched
      for relatively short durations, we plan to undertake a long-term study of
      spontaneous switching which is appropriately powered and includes non-switchers
      as a control group. METHODS/DESIGN: Healthy adult smokers aged 21-64 years will
      be enrolled into this 5-year non-residential, multicentre study across 10 cities
      in Germany. They will be assessed at 10 timepoints with 6 month intervals during
      which inclusion criteria will be reassessed and spent cigarette filter tips,
      saliva and 24 h urine samples will be collected. These samples will be used to
      determine average daily cigarette consumption, estimate mouth-level exposure to
      tar and nicotine and measure selected biomarkers of exposure, respectively.
      Spontaneous changes in subjects' preferred cigarette products and any consequent
      change in tar or nicotine yield will be monitored. Subjects will be required to
      complete questionnaires on quality of life, smoking behaviours, smoking-related
      sensory attributes and recent life changes. DISCUSSION: The planned study is
      anticipated to contribute to understanding smokers' behaviours and their
      consequent exposure to smoke constituents. It will also allow assessment of
      compensatory changes in their behaviour following spontaneous switching of
      cigarette product smoked. Data from this study are expected to provide insights
      into study design and conduct for non-clinical assessment of smokers' exposure as
      part of post marketing surveillance programmes. TRIAL REGISTRATION: Current
      Controlled Trials Database reference ISRCTN95019245.

PMID- 24725995
TI  - The use and misuse of animal analog models of human pregnancy disorders.
AB  - It has been suggested that the differences between placentation in humans and
      rodents, such as mice, are sufficient to render human pregnancy unique and to
      justify ignoring data generated using mice. Detailed examination of the placenta
      decidua interaction and decidual NK cell composition in humans, and mice, show
      that the principles are the same. Indeed, the rat placenta is useful in showing
      an intermediary arrangement between humans and mice. This is consistent with the
      thesis of Darwin that structures of older species evolve with development of new
      species to provide a survival advantage. Molecular details may differ between
      species, but also between individuals given gene polymorphisms. Human data on
      interaction of HLA-C2 with NK cell KIR receptors has been used to suggest that
      human pregnancy problems such as recurrent miscarriage, fetal growth retardation,
      and pre-eclampsia are due to lack of activation of true uterine NK cell (TuNK)
      functions that promote trophoblast cell growth and invasion which prevents such
      problems. But when TuNKs bear certain KIR phenotypes, pathology results. It is
      shown that such mechanisms could only be pertinent in less than one-third of
      recurrent miscarriage patients. Activated blood-type NK cells that enter the
      uterus (BuNKs) remain the major effector of pregnancy loss in humans, and this is
      consistent with data from the mouse. The importance of activated BuNKs in pre
      eclampsia and fetal growth retardation merits further investigation as pre
      eclampsia and fetal growth restriction are also manifest in the CBAxDBA/2 mouse
      model where activated NK cells are the initiator of abortions. 

PMID- 24725996
TI  - Comparative analysis of NK cell subsets in menstrual and peripheral blood of
      patients with unexplained recurrent spontaneous abortion and fertile subjects.
AB  - Natural killer (NK) cells play a fundamental role in maintaining pregnancy. Based
      on the availability and non-invasive method of collection of menstrual blood
      (MB), here we investigated for the first time a comparative analysis of NK cell
      subsets in MB and peripheral blood (PB) of women with recurrent spontaneous
      abortion (RSA) and fertile women. PB and MB of healthy fertile (n=15) and RSA
      women (n=15) were sampled simultaneously on the second day of the menstrual
      cycle. Proportions of CD56+CD3-CD16+/-, CD56+CD3-CCR7+/-, and CD56+CD3-CD45RO+/-
      cells were analyzed using flow cytometry. In the MB of both groups, proportions
      of CD16+ and CD45RO- NK cells were significantly lower than in the PB. In
      parallel, CD56+CD16+CCR7- and CCR7+ cells were present in significantly smaller
      amounts in MB than in PB. However, the amounts of CD56+CD16-CCR7- and CCR7+ cells
      were greater in MB. In comparison to the fertile group, the percentage of MB
      CD45RO+ NK cells was significantly lower and frequencies of PB CD16-, CD45RO- and
      CD56+CD16+CCR7+ subsets were significantly higher in RSA patients. Different
      subsets of NK cells are differentially distributed in MB in comparison with PB in
      women with RSA and fertile subjects. Population differences of NK cell subsets in
      RSA patients and normal controls were more clearly reflected at the systemic
      level. 

PMID- 24725997
TI  - Temporal pattern of questing tick Ixodes ricinus density at differing elevations
      in the coastal region of western Norway.
AB  - BACKGROUND: Climate change can affect the activity and distribution of species,
      including pathogens and parasites. The densities and distribution range of the
      sheep tick (Ixodes ricinus) and it's transmitted pathogens appears to be
      increasing. Thus, a better understanding of questing tick densities in relation
      to climate and weather conditions is urgently needed. The aim of this study was
      to test predictions regarding the temporal pattern of questing tick densities at
      two different elevations in Norway. We predict that questing tick densities will
      decrease with increasing elevations and increase with increasing temperatures,
      but predict that humidity levels will rarely affect ticks in this northern,
      coastal climate with high humidity. METHODS: We described the temporal pattern of
      questing tick densities at ~100 and ~400 m a.s.l. along twelve transects in the
      coastal region of Norway. We used the cloth lure method at 14-day intervals
      during the snow-free season to count ticks in two consecutive years in 20 m2
      plots. We linked the temporal pattern of questing tick densities to local
      measurements of the prevailing weather. RESULTS: The questing tick densities were
      much higher and the season was longer at ~100 compared to at ~400 m a.s.l. There
      was a prominent spring peak in both years and a smaller autumn peak in one year
      at ~100 m a.s.l.; but no marked peak at ~400 m a.s.l. Tick densities correlated
      positively with temperature, from low densities <5 degrees C, then increasing and
      levelling off >15-17 degrees C. We found no evidence for reduced questing
      densities during the driest conditions measured. CONCLUSIONS: Tick questing
      densities differed even locally linked to elevation (on the same hillside, a few
      kilometers apart). The tick densities were strongly hampered by low temperatures
      that limited the duration of the questing seasons, whereas the humidity appeared
      not to be a limiting factor under the humid conditions at our study site. We
      expect rising global temperatures to increase tick densities and lead to a
      transition from a short questing season with low densities in the current cold
      and sub-optimal tick habitats, to longer questing seasons with overall higher
      densities and a marked spring peak.

PMID- 24725998
TI  - The use of Taqman genotyping assays for rapid confirmation of beta-thalassaemia
      mutations in the Malays: accurate diagnosis with low DNA concentrations.
AB  - INTRODUCTION: In Malaysia, beta-thalassaemia is a common inherited blood disorder
      in haemoglobin synthesis with a carrier rate of 4.5%. Currently, PCR
      incorporating techniques such as amplification refractory mutation system (ARMS)
      or reverse dot blot hybridization (RDBH) are used in beta-thalassaemia mutation
      detection. ARMS allows single-mutation identification using two reactions, one
      for wild type and another for mutant alleles. RDBH requires probe immobilization
      and optimization of hybridization and washing temperatures which is time
      consuming. The aim of our study was to investigate whether beta-thalassaemia
      mutations can be identified in samples with low DNA concentrations. METHODS:
      Genotype identification of common beta-thalassaemia mutations in Malays was
      carried out using Taqman genotyping assays. RESULTS: Results show that the Taqman
      assays allow mutation detection with DNA template concentrations as low as 2-100
      ng. In addition, consistent reproducibility was observed in the Taqman assays
      when repeated eight times and at different time intervals. CONCLUSION: The
      developed sensitive Taqman assays allow molecular characterization of beta
      thalassaemia mutations in samples with low DNA concentrations. The Taqman
      genotyping assays have potential as a diagnostic tool for foetal blood, chorionic
      villi or pre-implantation genetic diagnosis where DNA is limited and precious.

PMID- 24725999
TI  - Rapid evolution of avirulence genes in rice blast fungus Magnaporthe oryzae.
AB  - BACKGROUND: Rice blast fungus Magnaporthe oryzae is one of the most devastating
      pathogens in rice. Avirulence genes in this fungus share a gene-for-gene
      relationship with the resistance genes in its host rice. Although numerous
      studies have shown that rice blast R-genes are extremely diverse and evolve
      rapidly in their host populations, little is known about the evolutionary
      patterns of the Avr-genes in the pathogens. RESULTS: Here, six well-characterized
      Avr-genes and seven randomly selected non-Avr control genes were used to
      investigate the genetic variations in 62 rice blast strains from different parts
      of China. Frequent presence/absence polymorphisms, high levels of nucleotide
      variation (~10-fold higher than non-Avr genes), high non-synonymous to synonymous
      substitution ratios, and frequent shared non-synonymous substitution were
      observed in the Avr-genes of these diversified blast strains. In addition, most
      Avr-genes are closely associated with diverse repeated sequences, which may
      partially explain the frequent presence/absence polymorphisms in Avr-genes.
      CONCLUSION: The frequent deletion and gain of Avr-genes and rapid non-synonymous
      variations might be the primary mechanisms underlying rapid adaptive evolution of
      pathogens toward virulence to their host plants, and these features can be used
      as the indicators for identifying additional Avr-genes. The high number of
      nucleotide polymorphisms among Avr-gene alleles could also be used to distinguish
      genetic groups among different strains.

PMID- 24726000
TI  - BK polyomavirus-specific cellular immune responses are age-dependent and strongly
      correlate with phases of virus replication.
AB  - BK polyomavirus (BKPyV) infection is widespread and typically asymptomatic during
      childhood, but may cause nephropathy in kidney transplant recipients. However,
      there is only limited knowledge on BKPyV-specific immunity in children and
      adults, and its role in BKPyV-replication and disease posttransplant. We
      therefore characterized BKPyV-specific immunity from 122 immunocompetent
      individuals (1-84 years), 38 adult kidney recipients with (n = 14) and without
      BKPyV-associated complications (n = 24), and 25 hemodialysis (HD) patients. Blood
      samples were stimulated with overlapping peptides of BKPyV large-T antigen and
      VP1 followed by flow-cytometric analysis of activated CD4 T cells expressing
      interferon-gamma, IL-2 and tumor necrosis factor-alpha. Antibody-levels were
      determined using enzyme-linked immunosorbent assay. Both BKPyV-IgG levels and
      BKPyV-specific CD4 T cell frequencies were age-dependent (p = 0.0059) with
      maximum levels between 20 and 30 years (0.042%, interquartile range 0.05%).
      Transplant recipients showed a significantly higher BKPyV-specific T cell
      prevalence (57.9%) compared to age-matched controls (21.7%) or HD patients (28%,
      p = 0.017). Clinically relevant BKPyV-replication was associated with elevated
      frequencies of BKPyV-specific T cells (p = 0.0002), but decreased percentage of
      cells expressing multiple cytokines (p = 0.009). In conclusion, BKPyV-specific
      cellular immunity reflects phases of active BKPyV-replication either after
      primary infection in childhood or during reactivation after transplantation.
      Combined analysis of BKPyV-specific T cell functionality and viral loads may
      improve individual risk assessment.

PMID- 24726001
TI  - Diagnosis, prognosis and therapeutic role of circulating miRNAs in cardiovascular
      diseases.
AB  - Cardiovascular diseases (CVD) are the leading cause of morbidity and mortality in
      the world. Although much progress has been made for cardiovascular diseases in
      diagnosis, treatment and prognosis during the past two decades, the clinical need
      for a novel diagnostic biomarker and new therapeutic interventions to decrease
      the cardiovascular disease incidence is ongoing. MicroRNAs (miRNAs) are
      endogenous, small (~22 nucleotides), single-stranded, non-coding RNAs that
      regulate gene expression and are detectable in whole blood, serum, plasma, urine
      and other body fluids in a highly stable form. Accumulating evidence suggests
      that miRNAs are potential novel biomarkers with high sensitivity for early
      diagnosis and modern treatment for cardiovascular diseases. Altered circulating
      miRNAs expressions have been reported in acute myocardial infarction (AMI), acute
      coronary syndrome (ACS), stable coronary artery disease, heart failure,
      atherosclerosis, essential hypertension and stroke. In the present review, we
      examine more recent data regarding circulating miRNAs and their potential roles
      in diagnosis, prognosis and therapeutic strategies for cardiovascular diseases.
      In addition, we briefly present our own recent experience in detecting
      circulating miRNAs, and the significance of these miRNAs in AMI prognosis.

PMID- 24726002
TI  - Predicting adverse outcomes in elective coronary artery bypass graft surgery
      using pre-operative troponin I levels.
AB  - BACKGROUND: Cardiac troponins are frequently measured as part of the pre
      operative work-up of patients prior to coronary artery bypass graft surgery
      (CABG). The utility of measuring these levels in elective patients, and the
      clinical implication of an abnormal result are unclear. The following study
      investigates the relationship between cardiac troponin I (cTnI) measured as part
      of a routine pre-operative work-up and outcomes following CABG. METHODS: From
      January 2010 to December 2012, 378 patients underwent isolated, elective CABG and
      had cTnI measured prospectively, as part of their pre-operative work-up. Patients
      were divided into normal (Group I) and elevated (Group II) cTnI groups. Pre
      operative, operative and post-operative data were obtained from our institution's
      prospectively collected database. RESULTS: Elevated cTnI was present in 47
      patients (12.4%) pre-operatively. Intra-operative variables did not differ
      between the elevated cTnI and control groups. Both 30-day mortality (Group I:
      0.9% v Group II: 6.4%, p=0.03) and cardiac arrest (Group I: 1.5% v Group II:
      8.5%, p=0.01) were significantly more frequent in the elevated cTnI group. In
      multivariable analysis, elevated cTnI remained a predictor for cardiac arrest (OR
      5.8, 95% CI 1.2 - 29.2). CONCLUSIONS: Patients presenting for elective CABG
      frequently have elevated cTnI on pre-operative work-up. These patients may be at
      a greater risk of 30-day mortality and cardiac arrest. Routine pre-operative
      measurement of cTnI may alert clinicians to a higher operative risk.

PMID- 24726003
TI  - [Two cases of pneumocephalus following noninvasive continuous positive airway
      ventilation after transsphenoidal neurosurgery].
AB  - The early use of continuous positive airway pressure ventilation has been shown
      to be effective and is recommended for patients with obstructive sleep apnea. The
      complications of continuous positive airway pressure ventilation are not well
      described. We report two cases of pneumocephalus following the use of continuous
      positive airway pressure ventilation after transsphenoidal surgery. One patient
      had an obstructive sleep apnea and the other suffered acute respiratory failure.
      In both cases, pneumocephalus caused major morbidity and required specific
      treatment and prolonged considerably hospital stay. Based on these observations
      we believe new precautions in the use of noninvasive continuous positive airway
      pressure ventilation should be recommended. 

PMID- 24726004
TI  - Mechanochemical endovenous Ablation versus RADiOfrequeNcy Ablation in the
      treatment of primary great saphenous vein incompetence (MARADONA): study protocol
      for a randomized controlled trial.
AB  - BACKGROUND: Radiofrequency ablation (RFA) is associated with an excellent outcome
      in the treatment of great saphenous vein (GSV) incompetence. The use of thermal
      energy as a treatment source requires the instillation of tumescence anesthesia.
      Mechanochemical endovenous ablation (MOCA) combines mechanical endothelial
      damage, using a rotating wire, with the infusion of a liquid sclerosant.
      Tumescence anesthesia is not required. Preliminary experiences with MOCA showed
      good results and low post-procedural pain. METHODS/DESIGN: The MARADONA
      (Mechanochemical endovenous Ablation versus RADiOfrequeNcy Ablation) trial is a
      multicenter randomized controlled trial in which 460 patients will be randomly
      allocated to MOCA or RFA. All patients with primary GSV incompetence who meet the
      eligibility criteria will be invited to participate in this trial. The primary
      endpoints are anatomic and clinical success at a one-year follow-up, and post
      procedural pain. The secondary endpoints are technical success, complications,
      operation time, procedural pain, disease-specific quality of life, time taken to
      return to daily activities and/or work, and cost-efficiency analyses after RFA or
      MOCA. Both groups will be evaluated on an intention to treat base. DISCUSSION:
      The MARADONA trial is designed to show equal results in anatomic and clinical
      success after one year, comparing MOCA with RFA. In our hypothesis MOCA has an
      equal anatomic and clinical success compared with RFA, with less post-procedural
      pain. TRIAL REGISTRATION: Clinicaltrials NCT01936168.

PMID- 24726005
TI  - Review of an established UK home phototherapy service 1998-2011: improving access
      to a cost-effective treatment for chronic skin disease.
AB  - OBJECTIVES: To review the Tayside home phototherapy service, including numbers of
      patients treated, diagnoses and outcomes, side-effects and safety, cost
      effectiveness and absolute costs. To consider why home or outpatient phototherapy
      is not available to all patients who might benefit and how this could be
      addressed. STUDY DESIGN: Observational and cost analysis. METHODS: Analysis of
      the Tayside home phototherapy database 1998 and 2011, home phototherapy patient
      questionnaires, outcome data, costs and a comparison with outpatient
      phototherapy. Review of literature and current national guidelines for
      phototherapy, traditional systemic and biologic therapies for psoriasis. RESULTS:
      298 courses of home narrowband UVB (NB-UVB) phototherapy were undertaken by 212
      patients between 1998 and 2011, five courses in 1998 increasing to 36 in 2011.
      The main diagnoses treated were psoriasis (72%), atopic dermatitis (8%), and
      desensitization of photodermatosis (7%). For psoriasis, 74.5% achieved clearance
      or minimal residual activity in a median of 30 exposures (range 10-60). The
      estimated costs to the hospital ranged from L229 to L314 per course (L307 to L422
      per effective course for psoriasis), compared with L114 for out-patient therapy
      (L149 per effective course for psoriasis). The total cost to society (hospital
      and patient costs) is around L410 per course, compared to an estimated L550 for
      outpatient therapy for this group of patients. Treatment was well tolerated,
      erythema rates were similar to outpatient therapy, there were no complaints and
      the vast majority would choose home over outpatient phototherapy if required in
      the future. CONCLUSIONS: Hospital supervised home phototherapy appears as safe
      and effective as outpatient therapy and provides equality of access for patients
      who cannot attend for outpatient therapy. These patients may otherwise be
      inadequately treated or given more costly and higher risk systemic therapies,
      particularly for psoriasis. Commissioners and clinicians involved in dermatology
      services should provide accessible phototherapy for all patients who might
      benefit, utilizing home phototherapy where outpatient access is not possible.

PMID- 24726006
TI  - The food retail environment and its use in a deprived, urban area of Scotland.
AB  - OBJECTIVES: This study sought to describe the food retail environment and its use
      in a deprived urban area in Scotland by mapping all food outlets and determining
      where residents do their main food shopping as well as investigating the
      availability of fresh fruit and vegetables (F&V) (as an indicator of healthy
      eating) and takeaway food. STUDY DESIGN: Cross-sectional study. METHODS: The food
      retail environment, the number, size and food availability of all food outlets,
      was mapped in Viewpark, a small community located to the east of Glasgow.
      Subsequently a validated questionnaire was used to determined food shopping usage
      and habits. RESULTS: There was high availability of common fresh fruit and
      vegetables (F&V) and very high availability of fast food outlets. Only 9% of the
      sample shopped solely at local food outlets within Viewpark whilst 91% shopped at
      a large supermarket outside Viewpark (n = 106). Walking was significantly
      negatively associated (B = -3.555, P = 0.008) with shopping outside the
      community. The majority of respondents (80%) reported buying F&V weekly and 57%
      purchased takeaways at least once a week - these individuals were employed, over
      45 years old and had at least one child. CONCLUSIONS: The use of the local retail
      environment in a deprived community is influenced by car accessibility.

PMID- 24726007
TI  - [Use of a free antero-lateral thigh flap for two-stage reconstruction of a large
      thoracic defect].
AB  - In case of extremely large thoracic full-thickness defects where no pedicled flap
      is available, very large free flaps are sometimes the only options. Dealing with
      such full-thickness defects where failure of the flap could be lethal, Servant
      and al described the concept of "two stage free flap" using Latissimus Dorsi
      muscular or myocutaneous flap. We present a reconstruction of a wide right
      posterior trunk radionecrosis with exposure of an underlying infected prosthesis
      using this two-stage free flap strategy with a fasciocutaneous antero-lateral
      thigh flap. 

PMID- 24726008
TI  - [Tolerance and efficacy of lipomodelling as an element of breast symmetry in
      breast reconstruction].
AB  - AIM OF THE STUDY: Fat transfer significantly improved results in breast
      reconstruction. Final breast symmetry is very important in breast reconstruction,
      but sometimes, the result is not perfect with usual techniques. The aim of this
      study is to evaluate the tolerance and efficacy of lipomodelling as a
      complementary technique for breast symmetrisation. MEANS AND METHODS: In this
      study, 150 patients had controlateral breast symmetrisation after breast
      reconstruction, using or completed with fat transfer. Patients were clinically
      evaluated one year after surgery. Age, BMI, harvested, purified and transferred
      fat volumes, and postoperatory complications were recorded. Morphological
      outcomes were evaluated by the surgeon as: very good, good, average or bad.
      Patients rated their degree of satisfaction as: very satisfying, satisfying, poor
      or bad. RESULTS: We found out that 98.6 % of morphological results were good or
      very good, and 86.6 % of the patients were satisfied or very satisfied with the
      result. Complications were rare (2 % of cytosteatonecrotic lesions). CONCLUSION:
      Lipomodelling in native breast symmetrisation after reconstruction is a powerful
      technique because it allows to increase volume of a hypoplastic controlateral
      breast, to ameliorate its shape, and to finally enhance mammoplasty result by
      correcting persisting localized volume defects. It definitively is a major
      therapeutic tool for enhancing breast reconstruction outcomes.

PMID- 24726009
TI  - A case of recurrent, bilateral ovarian mature teratoma in a young woman.
AB  - BACKGROUND: Ovarian mature cystic teratomas are common, benign, pelvic tumors
      that are easily detected by pelvic ultrasonography. However, patients with
      recurrent teratomas are rarely noted, and cases of bilateral teratomas are even
      less common. CASE PRESENTATION: A young woman with a recurrent, right ovarian
      teratoma had previously undergone surgical removal 2 times. After the second
      surgery, she underwent regular out-patient follow-up, and no residual tumor was
      observed. However, 3 years after the second surgery, she developed recurrent,
      bilateral ovarian teratomas, in conjunction with elevated carbohydrate antigen
      125 levels. CONCLUSION: Routine checking of the contralateral ovary during the
      surgical procedure along with frequent postoperative pelvic sonography for both
      ovaries in the patient at high recurrence rich is necessary. Additionally, the
      features of that kind tumor may mislead the surgeon into performing more
      extensive surgery that might compromise the fertility of young patients.

PMID- 24726010
TI  - Assessing the quality of record keeping for cesarean deliveries: results from a
      multicenter retrospective record review in five low-income countries.
AB  - BACKGROUND: Reliable, timely information is the foundation of decision making for
      functioning health systems; the quality of decision making rests on quality data.
      Routine monitoring, reporting, and review of cesarean section (CS) indications,
      decision-to-delivery intervals, and partograph use are important elements of
      quality improvement for maternity services. METHODS: In 2009 and 2010, a sample
      of CS records from calendar year 2008 was reviewed at nine facilities in
      Bangladesh, Guinea, Mali, Niger, and Uganda. Data from patient records and
      hospital registers were collected on key aspects of care such as timing of key
      events, indications, partograph use, maternal and fetal outcomes. Qualitative
      interviews were conducted with key informants at all study sites to provide
      contextual background about CS services and record keeping practices. RESULTS: A
      total of 2,941 records were reviewed and 57 key informant interviews were
      conducted. Patient record-keeping systems were of varying quality across study
      sites: at five sites, more than 20% of records could not be located. Across all
      sites, patient files were missing key aspects of CS care: timing of key events
      (e.g., examination, decision to perform CS), administration of prophylactic
      antibiotics, maternal complications, and maternal and fetal outcomes. Rates of
      partograph use were low at six sites: 0 to 23.9% of patient files at these sites
      had a completed partograph on file, and among those found, 2.1% to 65.1% were
      completed correctly. Information on fetal outcomes was missing in up to 40% of
      patient files. CONCLUSIONS: Deficits in the quality of CS patient records across
      a broad range of health facilities in low-resource settings in four sub-Saharan
      Africa countries and Bangladesh indicate an urgent need to improve record
      keeping.

PMID- 24726011
TI  - Special Issue about Natural Resources--part II.

PMID- 24726013
TI  - How relatives of patients with head and neck cancer experience pain, disease
      progression and treatment: a qualitative interview study.
AB  - PURPOSE: This study of relatives to patients with head and neck cancer (HNC)
      treated with radiotherapy describes how the relatives experienced the patient's
      situation, especially with respect to pain, and how the relatives themselves
      experienced the situation. METHODS: Semi-structured interviews of 21 relatives to
      HNC patients who suffered from pain were conducted, and a qualitative content
      analysis was performed. RESULTS: The relatives experienced that the patients
      suffered from physical, psychological, and social pain. A dark picture consisting
      of lack of participation and knowledge, psychological distress, and lack of
      support were reported. Thus, a main category: relatives struggle with loved one's
      pains related to head and neck cancer treatment and with their own demanding
      situation - was based on the following four categories: inability to relieve and
      comprehend the physical suffering of the patients; overwhelming emotions were
      experienced that affect the patients and the relatives themselves; in need of
      support from the health care service; and altered daily activities and family
      roles due to illness and treatment. CONCLUSION: In patients physical,
      psychological, and social pain were prominent and in relatives psychological
      distress, lack of knowledge and support were experienced. Thus, to reduce pain
      and anxiety in patients and relatives, the health care professionals should
      provide relevant knowledge about pain management. The health care professionals
      should also provide educational interventions that address the psychological and
      social factors that impact pain for HNC patients and their relatives. Well
      thought supporting care and easily accessible information about practical
      concerns should be offered to HNC patients and their relatives.

PMID- 24726012
TI  - MART-1 peptide vaccination plus IMP321 (LAG-3Ig fusion protein) in patients
      receiving autologous PBMCs after lymphodepletion: results of a Phase I trial.
AB  - BACKGROUND: Immunotherapy offers a promising novel approach for the treatment of
      cancer and both adoptive T-cell transfer and immune modulation lead to regression
      of advanced melanoma. However, the potential synergy between these two strategies
      remains unclear. METHODS: We investigated in 12 patients with advanced stage IV
      melanoma the effect of multiple MART-1 analog peptide vaccinations with (n = 6)
      or without (n = 6) IMP321 (LAG-3Ig fusion protein) as an adjuvant in combination
      with lymphodepleting chemotherapy and adoptive transfer of autologous PBMCs at
      day (D) 0 (Trial registration No: NCT00324623). All patients were selected on the
      basis of ex vivo detectable MART-1-specific CD8 T-cell responses and immunized at
      D0, 8, 15, 22, 28, 52, and 74 post-reinfusion. RESULTS: After immunization, a
      significant expansion of MART-1-specific CD8 T cells was measured in 83% (n =
      5/6) and 17% (n = 1/6) of patients from the IMP321 and control groups,
      respectively (P < 0.02). Compared to the control group, the mean fold increase of
      MART-1-specific CD8 T cells in the IMP321 group was respectively >2-, >4- and >6
      fold higher at D15, D30 and D60 (P < 0.02). Long-lasting MART-1-specific CD8 T
      cell responses were significantly associated with IMP321 (P < 0.02). At the peak
      of the response, MART-1-specific CD8 T cells contained higher proportions of
      effector (CCR7- CD45RA+/-) cells in the IMP321 group (P < 0.02) and showed no
      sign of exhaustion (i.e. were mostly PD1-CD160-TIM3-LAG3-2B4+/-). Moreover,
      IMP321 was associated with a significantly reduced expansion of regulatory T
      cells (P < 0.04); consistently, we observed a negative correlation between the
      relative expansion of MART-1-specific CD8 T cells and of regulatory T cells.
      Finally, although there were no confirmed responses as per RECIST criteria, a
      transient, 30-day partial response was observed in a patient from the IMP321
      group. CONCLUSIONS: Vaccination with IMP321 as an adjuvant in combination with
      lymphodepleting chemotherapy and adoptive transfer of autologous PBMCs induced
      more robust and durable cellular antitumor immune responses, supporting further
      development of IMP321 as an adjuvant for future immunotherapeutic strategies.

PMID- 24726015
TI  - The effects of cannabinoid administration on sleep: a systematic review of human
      studies.
AB  - This paper reviews the literature regarding the effects of cannabinoid
      administration on sleep in humans. A literature search using a set of cannabinoid
      and sleep-related terms was conducted across eight electronic databases. Human
      studies that involved the administration of cannabinoids and at least one
      quantitative sleep-related measure were included. Review papers, opinion pieces,
      letters or editorials, case studies (final N < 7), published abstracts, posters,
      and non-English papers were excluded. Thirty-nine publications were included in
      the review. Findings were mixed and showed various effects of cannabinoid
      administration on several aspects of sleep. Methodological issues in the majority
      of studies to date, however, preclude any definitive conclusion.

PMID- 24726014
TI  - Research progress on surface antigen 1 (SAG1) of Toxoplasma gondii.
AB  - Toxoplasma gondii is an obligate intracellular parasitic protozoan that has a
      wide host range and causes a zoonotic parasitosis called toxoplasmosis. This
      infection causes significant morbidity, costs for care and loss of productivity
      and suffering. The most effective measures to minimize this parasite's harm to
      patients are prompt diagnosis and treatment and preventing infection. A parasite
      surface antigen, SAG1, is considered an important antigen for the development of
      effective diagnostic tests or subunit vaccines. This review covers several
      aspects of this antigen, including its gene structure, contribution to host
      invasion, mechanisms of the immune responses and its applications for diagnosis
      and vaccine development. This significant progress on this antigen provides
      foundations for further development of more effective and precise approaches to
      diagnose toxoplasmosis in the clinic, and also have important implications for
      exploring novel measures to control toxoplasmosis in the near future. 

PMID- 24726016
TI  - [Apparent life-threatening events due to cow's milk allergy in infants].
AB  - The analysis of an apparent life-threatening event is mainly based on the
      clinical approach. When the event occurs after a meal, the diagnosis of acid
      gastroesophageal reflux complicated by esophagitis is suspected first. Cow's milk
      protein allergy is suspected when the event occurs during weaning from
      breastfeeding or when it is accompanied by urticaria or relapses when cow's milk
      is reintroduced. We report on two cases of an apparent life-threatening event
      associated with cow's milk protein allergy, whose symptoms and first diagnostic
      approach initially delayed diagnosis. Clinical manifestations of food allergy
      need to be known in order to avoid errors in diagnostic orientation and therapy,
      which may be responsible for more severe recurrences. 

PMID- 24726018
TI  - How adolescents perceive their communities: a qualitative study that explores the
      relationship between health and the physical environment.
AB  - BACKGROUND: The Well-Being of Adolescents in Vulnerable Environments (WAVE) study
      was conducted among adolescents aged 15-19 years in Baltimore, Ibadan,
      Johannesburg, New Delhi, and Shanghai to examine perceived factors related to
      their health. A preliminary analysis of the data, unexpectedly, revealed that the
      influence of the physical environment on adolescent health was a dominant theme
      across every site examined. To explore this further, this paper analyzed the
      specific components of the physical environment that were perceived to influence
      health, and how they contributed to various health outcomes across sites.
      METHODS: Researchers in each site conducted in-depth interviews among
      adolescents; community mapping and focus groups among adolescents; a Photovoice
      methodology, in which adolescents were trained in photography and took photos of
      the meaning of 'health' in their communities; and key informant interviews among
      adults who work with young people. A total 529 participants from across the sites
      were included in the analysis. RESULTS: Findings showed that while there was
      surprising uniformity in how adolescents characterized their physical
      environment, perceived health outcomes related to the physical environment varied
      by site and gender. In Baltimore and Johannesburg, vacant homes and the lack of
      recreation facilities were perceived to impact on sexual and reproductive health
      problems for girls, while among boys they contributed to drugs and violence. In
      Shanghai, New Delhi, and Ibadan, garbage and trash observed in their communities
      were perceived to have a higher impact on infectious and chronic diseases.
      CONCLUSIONS: As the world continues to urbanize, our study points to a strong
      need to examine how the physical aspects of a living environment contribute to
      the health of adolescents. Specific aspects, such as housing, safety, garbage,
      and recreational spaces must all be examined as possible pathways for making
      improvements to health of adolescents, particularly among those living in poor
      urban environments.

PMID- 24726017
TI  - Anomalous diffraction in crystallographic phase evaluation.
AB  - X-ray diffraction patterns from crystals of biological macromolecules contain
      sufficient information to define atomic structures, but atomic positions are
      inextricable without having electron-density images. Diffraction measurements
      provide amplitudes, but the computation of electron density also requires phases
      for the diffracted waves. The resonance phenomenon known as anomalous scattering
      offers a powerful solution to this phase problem. Exploiting scattering
      resonances from diverse elements, the methods of MAD (multiwavelength anomalous
      diffraction) and SAD (single-wavelength anomalous diffraction) now predominate
      for de novo determinations of atomic-level biological structures. This review
      describes the physical underpinnings of anomalous diffraction methods, the
      evolution of these methods to their current maturity, the elements, procedures
      and instrumentation used for effective implementation, and the realm of
      applications. 

PMID- 24726019
TI  - Genome-wide SNPs lead to strong signals of geographic structure and relatedness
      patterns in the major arbovirus vector, Aedes aegypti.
AB  - BACKGROUND: Genetic markers are widely used to understand the biology and
      population dynamics of disease vectors, but often markers are limited in the
      resolution they provide. In particular, the delineation of population structure,
      fine scale movement and patterns of relatedness are often obscured unless
      numerous markers are available. To address this issue in the major arbovirus
      vector, the yellow fever mosquito (Aedes aegypti), we used double digest
      Restriction-site Associated DNA (ddRAD) sequencing for the discovery of genome
      wide single nucleotide polymorphisms (SNPs). We aimed to characterize the new SNP
      set and to test the resolution against previously described microsatellite
      markers in detecting broad and fine-scale genetic patterns in Ae. aegypti.
      RESULTS: We developed bioinformatics tools that support the customization of
      restriction enzyme-based protocols for SNP discovery. We showed that our approach
      for RAD library construction achieves unbiased genome representation that
      reflects true evolutionary processes. In Ae. aegypti samples from three
      continents we identified more than 18,000 putative SNPs. They were widely
      distributed across the three Ae. aegypti chromosomes, with 47.9% found in
      intergenic regions and 17.8% in exons of over 2,300 genes. Pattern of their
      imputed effects in ORFs and UTRs were consistent with those found in a recent
      transcriptome study. We demonstrated that individual mosquitoes from Indonesia,
      Australia, Vietnam and Brazil can be assigned with a very high degree of
      confidence to their region of origin using a large SNP panel. We also showed that
      familial relatedness of samples from a 0.4 km2 area could be confidently
      established with a subset of SNPs. CONCLUSIONS: Using a cost-effective customized
      RAD sequencing approach supported by our bioinformatics tools, we characterized
      over 18,000 SNPs in field samples of the dengue fever mosquito Ae. aegypti. The
      variants were annotated and positioned onto the three Ae. aegypti chromosomes.
      The new SNP set provided much greater resolution in detecting population
      structure and estimating fine-scale relatedness than a set of polymorphic
      microsatellites. RAD-based markers demonstrate great potential to advance our
      understanding of mosquito population processes, critical for implementing new
      control measures against this major disease vector.

PMID- 24726020
TI  - Epidemiology of invasive mold infections in lung transplant recipients.
AB  - Invasive mold infections (IMIs) are a major source of morbidity and mortality
      among lung transplant recipients (LTRs), yet information regarding the
      epidemiology of IMI in this population is limited. From 2001 to 2006, multicenter
      prospective surveillance for IMIs among LTR was conducted by the Transplant
      Associated Infection Surveillance Network. The epidemiology of IMI among all LTRs
      in the cohort is reported. Twelve percent (143/1173) of LTRs under surveillance
      at 15 US centers developed IMI infections. The 12-month cumulative incidence of
      IMIs was 5.5%; 3-month all-cause mortality was 21.7%. Aspergillus caused the
      majority (72.7%)of IMIs; non-Aspergillus infections (39, 27.3%) included
      Scedosporium (5, 3.5%), mucormycosis (3, 2.1%) and "unspecified" or "other" mold
      infections (31, 21.7%). Late-onset IMI was common: 52% occurred within 1 year
      posttransplant (median 11 months, range 0-162 months). IMIs are common late-onset
      complications with substantial mortality in LTRs. LTRs should be monitored for
      late-onset IMIs and prophylactic agents should be optimized based on likely
      pathogen. 

PMID- 24726021
TI  - Intranasal delivery of nanoparticles encapsulating BPI3V proteins induces an
      early humoral immune response in mice.
AB  - Vaccine adjuvants are typically designed to stimulate both systemic and mucosal
      immune responses. Polymeric nanoparticles have been used as adjuvants in the
      development of vaccines against a number of viral pathogens and tested in
      laboratory animals. The objective of the study was to assess if synthetic bovine
      parainfluenza virus type-3 (BPI3V) peptide motifs and solubilised BPI3V proteins
      encapsulated in poly (dl-lactic-co-glycolide) (PLGA) nanoparticles (NPs) induce
      specific humoral immune responses in a mouse model following intranasal
      administration. BPI3V-specific and peptide specific IgG ELISAs were used to
      measure serum IgG levels to BPI3V. Intranasal delivery of PLGA nanoparticles
      encapsulating BPI3V proteins elicited an early, gradually increasing BPI3V
      specific IgG response that persisted over the subsequent 6 weeks, suggesting
      slow, persistent release of antigen. PLGA-BPI3V particles administered
      intranasally induced a stronger IgG antibody response at an earlier time point
      compared with solubilised BPI3V antigen alone. Such an approach could be deployed
      in the development of new generation vaccines.

PMID- 24726022
TI  - High-throughput multiplex MIRU-VNTR typing of Mycobacterium bovis.
AB  - Spoligotyping is the most widely used method for genotyping Mycobacterium bovis
      (M. bovis). However, its discriminatory power varies widely between countries.
      MIRU-VNTR typing could be a promising alternative, although it generally requires
      the time consuming and laborious simplex PCR assays using standard agarose gel
      electrophoresis. The accuracy of this approach depends on good standardization
      and a certain degree of expertise. This study presents a version of MIRU-VNTR
      based on three triplex PCRs with automatic allelic assignation of the products
      analyzed in capillary electrophoresis. The technique was prospectively applied to
      44 M. bovis and two Mycobacterium caprae (M. caprae) isolates, and 22 different
      MIRU-VNTRtypes were obtained; with spoligotyping, only 14 different types were
      obtained. The proposal makes it possible to shorten response times, automate
      procedures, and increase accuracy, thus minimizing errors in assigning genotypes.
      It would enable the switch from a standard limited method of genotyping M. bovis
      to a high-throughput discriminatory fingerprinting approach.

PMID- 24726023
TI  - Neurosensory deafness: Superficial siderosis of the central nervous system.

PMID- 24726024
TI  - [Surgical management of retrosternal goitre: experience of a Moroccan centre].
AB  - INTRODUCTION AND OBJECTIVES: This was a retrospective study reviewing 93 cases of
      retrosternal goitre (RG) operated in our department, with the aim of describing
      epidemiological and clinical data and discussing the surgical challenges of RG.
      PATIENTS AND METHODS: From January 2004 to December 2012, 35 men and 58 women
      presenting with RG had surgery. Eighty-nine cases (95.7%) underwent cervicotomy,
      and a sternotomy was mandatory in 4 cases (4.3%). Laryngoscopy was performed in
      all cases. A second preoperative laryngoscopy by a senior was mandatory for
      patients with hoarseness or dyspnea even if the initial laryngeal exam was
      normal. RESULTS: A cervical mass was noted in 81 cases (87.1%), dyspnea in 17
      cases (18.3%), dysphagia in 2 cases (2.1%), hoarseness in 7 cases (7.5%), partial
      vena cava syndrome in 2 cases and recurrent goitre was noted in 2 cases (2.1%)
      after previous thyroid resection. Mediastinal extension was on the left side in
      47 cases (50.5%), on the right side in 29 cases (31.2%) and bilateral in 17 cases
      (18.3%). A total thyroidectomy was performed in 86 cases (92.5%) and a unilateral
      isthmo-lobectomy was performed in 7 cases (7.5%). Mean goitre size was 9.3 cm.
      Postoperative complications were present in 9 cases (9.7%), 3 cases with
      hypoparathyroidism (3.2%) and 4 cases (4.3%) of recurrent nerve injury. There was
      no postoperative death. The histological study objectified 88 cases of
      multiheteronodular goitre, 4 cases of Basedow thyroid, and 1 case of thyroid
      carcinoma (papillary carcinoma). CONCLUSION: Our experience confirms that
      cervicotomy often allows removing goitre with a mediastinal extension. However,
      intraoperative enlargement may be necessary, with increased operating time,
      hospital stay and morbidity.

PMID- 24726025
TI  - When self-report diverges from performance: the usage of BIS-11 along with
      neuropsychological tests.
AB  - Impulsivity has been fractionated into multiple independent, but correlated,
      components. Personality and neuropsychological studies have consistently shown
      its multidimensional nature. Each theoretical approach uses different techniques
      such as self-report questionnaires and neuropsychological tests to assess
      impulsivity, respectively. Our main objective was to investigate if there is
      evidence of convergent validity for impulsivity as assessed by both types of
      measures. We administered the Barratt Impulsivity Scale 11 and two
      neuropsychological tests (Iowa Gambling Task and Continuous Performance Task) to
      266 participants to measure inhibition control and non-planning impulsivity
      dimensions. Results from an exploratory factorial analysis and group comparison
      indicated there was little evidence of convergent validity between the two types
      of measures. These findings are discussed in terms of impulsivity as a multi
      factorial construct as well as the specific instruments used for assessment.
      Implications for psychological theory and impulsivity assessment were also
      proposed. 

PMID- 24726027
TI  - The effect of trauma-focused therapy on the altered T cell distribution in
      individuals with PTSD: evidence from a randomized controlled trial.
AB  - Posttraumatic stress disorder (PTSD) is associated with a reduced ratio of naive
      cytotoxic T lymphocytes, an increased ratio of memory cytotoxic T lymphocytes,
      and a reduced proportion of FoxP3(+) regulatory T lymphocytes. This study
      investigated whether these immunological alterations are reversible through an
      evidence-based psychotherapeutic treatment. Therefore, 34 individuals with PTSD
      were randomly assigned to either a treatment condition of 12 sessions narrative
      exposure therapy (NET) or a waitlist control (WLC) group. PTSD symptoms were
      significantly reduced in the NET group, but not in the WLC group, four months
      post-therapy (effect size: Hedges' g = -1.61). One year after therapy, PTSD
      symptoms were improved even further in the NET group compared to baseline
      (Hedges' g = -1.96). This symptom improvement was mirrored in an increase in the
      originally reduced proportion of regulatory T cells (Tregs) in the NET group at
      the one-year follow-up, when comparing subgroups matched for baseline Treg
      numbers. However, no changes were found for the initially reduced proportion of
      CD45RA(+)CCR7(+) naive T lymphocytes. In conclusion, NET was effective in
      reducing trauma-related PTSD symptoms and had a positive effect on the proportion
      of Tregs cells, thus demonstrating an effect of psychotherapy on an immunological
      level. Yet, the shift in the proportion of naive and memory T lymphocytes in
      individuals with PTSD, discussed in the literature as a correlate of premature
      immunosenescence, was not reversible and thus might render these patients
      permanently more susceptible to infectious diseases.

PMID- 24726028
TI  - Thymidylate synthase polymorphisms in genomic DNA as clinical outcome predictors
      in a European population of advanced non-small cell lung cancer patients
      receiving pemetrexed.
AB  - BACKGROUND: We studied whether thymidylate synthase (TS) genotype has an
      independent prognostic/predictive impact on a European population of advanced non
      small cell lung cancer (NSCLC) patients receiving pemetrexed. METHODS: Twenty
      five patients treated with pemetrexed-based regimens were included. Genomic DNA
      was isolated prior to treatment. The variable number of tandem repeat (VNTR)
      polymorphisms, the G > C single nucleotide polymorphisms (SNP) and the TS 6-bp
      insertion/deletion (6/6) in the 3' untranslated region (UTR) polymorphisms were
      analyzed and correlated with overall response rate (ORR), progression-free
      survival (PFS), overall-survival (OS) and toxicity. RESULTS: The genotype +6/+6
      predicted a higher ORR among active/former smokers compared to +6/-6 genotype
      (100% vs. 50%; p = 0.085). Overall, the 3R/3R genotype predicted a higher ORR
      (100%) over the rest VNTR polymorphisms (p = 0.055). The presence of 3R/3R
      genotype significantly correlated with a superior ORR in patients without EGFR
      activating mutations (100%) compared to 2R/2R, 2R/3R and 3R/4R genotype (77.8%,
      33.3% and 0% respectively; p = 0.017). After a median follow-up of 21 months, a
      trend towards a better PFS, although not significant, was found among subjects
      showing 3R/3R polymorphisms (p = 0.089). A significantly superior OS was found in
      patients showing 3R/3R genotype rather than other VNTR polymorphisms (p = 0.019).
      No significant correlation with the toxicity was observed. CONCLUSION: In our
      series, 3R/3R polymorphism correlated with a superior OS. Also, this
      polymorphism, when associated to wild type EGFR, was related to a higher ORR to
      pemetrexed. Toxicity was not significantly correlated with a specific TS
      genotype.

PMID- 24726029
TI  - Acupuncture and moxibustion for lateral elbow pain: a systematic review of
      randomized controlled trials.
AB  - BACKGROUND: Acupuncture and moxibustion have widely been used to treat lateral
      elbow pain (LEP). A comprehensive systematic review of randomized controlled
      trials (RCTs) including both English and Chinese databases was conducted to
      assess the efficacy of acupuncture and moxibustion in the treatment of LEP.
      METHODS: Revised STRICTA (2010) criteria were used to appraise the acupuncture
      procedures, the Cochrane risk of bias tool was used to assess the methodological
      quality of the studies. A total of 19 RCTs that compared acupuncture and/or
      moxibustion with sham acupuncture, another form of acupuncture, or conventional
      treatment were included. RESULTS: All studies had at least one domain rated as
      high risk or uncertain risk of bias in the Cochrane risk of bias tool. Results
      from three RCTs of moderate quality showed that acupuncture was more effective
      than sham acupuncture. Results from 10 RCTs of mostly low quality showed that
      acupuncture or moxibustion was superior or equal to conventional treatment, such
      as local anesthetic injection, local steroid injection, non-steroidal anti-
      inflammatory drugs, or ultrasound. There were six low quality RCTs that compared
      acupuncture and moxibustion combined with manual acupuncture alone, and all
      showed that acupuncture and moxibustion combined was superior to manual
      acupuncture alone. CONCLUSION: Moderate quality studies suggest that acupuncture
      is more effective than sham acupuncture. Interpretations of findings regarding
      acupuncture vs. conventional treatment, and acupuncture and moxibustion combined
      vs. manual acupuncture alone are limited by the methodological qualities of these
      studies. Future studies with improved methodological design are warranted to
      confirm the efficacy of acupuncture and moxibustion for LEP.

PMID- 24726030
TI  - [The role of zolpidem in improving catatonic schizophrenia. Case report].

PMID- 24726031
TI  - [Treatment of acute full-thickness chondral defects with high molecular weight
      hyaluronic acid; an experimental model].
AB  - PURPOSE: To evaluate the effect of 2 different protocols of intra-articular
      hyaluronic acid (HA, hylan G-F20) to articular cartilage regeneration in acute
      full-thickness chondral defects. MATERIALS AND METHODS: Full-thickness chondral
      defects of 3 x 6 mm were performed into the lateral femoral condyles of New
      Zealand rabbits, treated with a single or three doses of HA. The animals were
      sacrified at 12 weeks and the regenerated tissue was evaluated by direct
      observation and histology with the ICRS scale. Macroscopically, in both groups
      treated with HA the defects were filled with irregular tissue with areas similar
      to hyaline cartilage and others in which depressed areas with exposed subchondral
      bone were observed. Histological analysis showed in both groups treated with HA a
      hyaline-like cartilage compared to control group. However, the score of the
      International Cartilage Repair Society (ICRS) scale did not show differences
      between the groups treated with HA. CONCLUSION: The use of single dose or 3 doses
      of AH in acute chondral lesions has a limited and similar benefit in articular
      cartilage regeneration.

PMID- 24726032
TI  - A feasibility study to inform the design of a randomized controlled trial to
      identify the most clinically and cost effective anticoagulation length with low
      molecular weight heparin in the treatment of cancer associated thrombosis
      (ALICAT): study protocol for a mixed-methods study.
AB  - BACKGROUND: Venous thromboembolism is common in patients with cancer and requires
      anticoagulation with low molecular weight heparin. Current data informs
      anticoagulation as far as six months, yet guidelines recommend anticoagulation
      beyond six months in patients who have locally advanced or metastatic cancer.
      This recommendation, based on expert consensus, has not been evaluated in a
      clinical study. ALICAT (Anticoagulation Length in Cancer Associated Thrombosis)
      is a feasibility study to identify the most clinically and cost effective length
      of anticoagulation with low molecular weight heparin in the treatment of cancer
      associated thrombosis. METHODS/DESIGN: ALICAT is a randomized multi-centre phase
      two mixed-methods study with three components: a randomized controlled trial,
      embedded qualitative study and a survey investigating pathways of care. The
      randomized controlled trial will compare ongoing low molecular weight heparin
      treatment for cancer-associated thrombosis versus cessation of low molecular
      weight heparin at six months treatment (current licensed practice) in patients
      with locally advanced or metastatic cancer. The embedded qualitative study will
      include focus groups with clinicians to investigate attitudes to recruiting to
      the study, identify the challenges of progressing to a full randomized controlled
      trial, and also semi-structured interviews with patients and relatives/carers to
      explore their attitudes towards participating in the study and potential barriers
      and concerns to participation. Finally, a UK wide survey exercise will be
      undertaken to develop a classification and enumeration system for the cancer
      associated thrombosis models and pathways of care. DISCUSSION: There is a lack of
      evidence determining the length of anticoagulation for patients with cancer
      associated thrombosis and subsequently treatment length varies. The ALICAT study
      will consider the feasibility of recruiting patients to a phase three trial.
      TRIAL REGISTRATION: Current Controlled Trials ISRCTN37913976.

PMID- 24726033
TI  - Are maturation, growth and lower extremity alignment associated with overuse
      injury in elite adolescent ballet dancers?
AB  - OBJECTIVE: To identify growth, maturation and biomechanical risk factors for
      overuse injury in elite adolescent ballet dancers. METHODS: Maturation (Tanner
      scale), growth (foot length change) and age at onset of menarche were recorded in
      elite adolescent ballet dancers. A modified knee valgus angle and lateral tilt of
      the pelvis were measured using 2D video during two dance movements (fondu, temps
      leve) to quantify lower extremity alignment. Overuse dance injuries were recorded
      by a physiotherapist. The injury rate ratio (RR) associated with each variable
      was estimated using over-dispersed Poisson regression modelling. RESULTS: Changes
      in right foot length (RR = 1.41, CI = 0.93-2.13), right knee angles during the
      fondu (RR = 0.68, CI = 0.45-1.03) and temps leve (RR = 0.72, CI = 0.53-0.98), and
      pelvic angles during the temps leve on the left (RR = 0.52, CI = 0.30-0.90) and
      fondu on the right (RR = 1.28, CI = 0.91-1.80) were associated with substantial
      changes in injury risk. CONCLUSIONS: Rate of growth in elite adolescent ballet
      dancers is likely associated with an increase in risk of lower extremity overuse
      injury and better right lower extremity alignment is likely associated with a
      reduction in risk of right lower extremity overuse injury.

PMID- 24726034
TI  - Clinical and genetic features of pediatric acute lymphoblastic leukemia in Down
      syndrome in the Nordic countries.
AB  - BACKGROUND: Children with Down syndrome (DS) have an increased risk for acute
      lymphoblastic leukemia (ALL). Although previous studies have shown that DS-ALL
      differs clinically and genetically from non-DS-ALL, much remains to be elucidated
      as regards genetic and prognostic factors in DS-ALL. METHODS: To address clinical
      and genetic differences between DS-ALL and non-DS-ALL and to identify prognostic
      factors in DS-ALL, we ascertained and reviewed all 128 pediatric DS-ALL diagnosed
      in the Nordic countries between 1981 and 2010. Their clinical and genetic
      features were compared with those of the 4,647 B-cell precursor (BCP) ALL cases
      diagnosed during the same time period. RESULTS: All 128 DS-ALL were BCP ALL,
      comprising 2.7% of all such cases. The 5-year event-free survival (EFS) and
      overall survival (OS) were significantly (P = 0.026 and P = 0.003, respectively)
      worse for DS-ALL patients with white blood cell counts >=50 * 109/l. The age
      distributions varied between the DS and non-DS cases, with age peaks at 2 and 3
      years, respectively; none of the DS patients had infant ALL (P = 0.029). The
      platelet counts were lower in the DS-ALL group (P = 0.005). Abnormal karyotypes
      were more common in non-DS-ALL (P < 0.0001), and there was a significant
      difference in the modal number distribution, with only 2% high hyperdiploid DS
      ALL cases (P < 0.0001). The 5-year EFS and 5-year OS were significantly worse for
      DS-ALL (0.574 and 0.691, respectively) compared with non-DS-ALL (0.783 and 0.894,
      respectively) in the NOPHO ALL-1992/2000 protocols (P < 0.001). CONCLUSIONS: The
      present study adds further support for genetic and clinical differences between
      DS-ALL and non-DS-ALL.

PMID- 24726036
TI  - Sepsis mortality prediction with the Quotient Basis Kernel.
AB  - OBJECTIVE: This paper presents an algorithm to assess the risk of death in
      patients with sepsis. Sepsis is a common clinical syndrome in the intensive care
      unit (ICU) that can lead to severe sepsis, a severe state of septic shock or
      multi-organ failure. The proposed algorithm may be implemented as part of a
      clinical decision support system that can be used in combination with the scores
      deployed in the ICU to improve the accuracy, sensitivity and specificity of
      mortality prediction for patients with sepsis. METHODOLOGY: In this paper, we
      used the Simplified Acute Physiology Score (SAPS) for ICU patients and the
      Sequential Organ Failure Assessment (SOFA) to build our kernels and algorithms.
      In the proposed method, we embed the available data in a suitable feature space
      and use algorithms based on linear algebra, geometry and statistics for
      inference. We present a simplified version of the Fisher kernel (practical Fisher
      kernel for multinomial distributions), as well as a novel kernel that we named
      the Quotient Basis Kernel (QBK). These kernels are used as the basis for
      mortality prediction using soft-margin support vector machines. The two new
      kernels presented are compared against other generative kernels based on the
      Jensen-Shannon metric (centred, exponential and inverse) and other widely used
      kernels (linear, polynomial and Gaussian). Clinical relevance is also evaluated
      by comparing these results with logistic regression and the standard clinical
      prediction method based on the initial SAPS score. RESULTS: As described in this
      paper, we tested the new methods via cross-validation with a cohort of 400 test
      patients. The results obtained using our methods compare favourably with those
      obtained using alternative kernels (80.18% accuracy for the QBK) and the standard
      clinical prediction method, which are based on the basal SAPS score or logistic
      regression (71.32% and 71.55%, respectively). The QBK presented a sensitivity and
      specificity of 79.34% and 83.24%, which outperformed the other kernels analysed,
      logistic regression and the standard clinical prediction method based on the
      basal SAPS score. CONCLUSION: Several scoring systems for patients with sepsis
      have been introduced and developed over the last 30 years. They allow for the
      assessment of the severity of disease and provide an estimate of in-hospital
      mortality. Physiology-based scoring systems are applied to critically ill
      patients and have a number of advantages over diagnosis-based systems. Severity
      score systems are often used to stratify critically ill patients for possible
      inclusion in clinical trials. In this paper, we present an effective algorithm
      that combines both scoring methodologies for the assessment of death in patients
      with sepsis that can be used to improve the sensitivity and specificity of the
      currently available methods.

PMID- 24726035
TI  - An extensive analysis of disease-gene associations using network integration and
      fast kernel-based gene prioritization methods.
AB  - OBJECTIVE: In the context of "network medicine", gene prioritization methods
      represent one of the main tools to discover candidate disease genes by exploiting
      the large amount of data covering different types of functional relationships
      between genes. Several works proposed to integrate multiple sources of data to
      improve disease gene prioritization, but to our knowledge no systematic studies
      focused on the quantitative evaluation of the impact of network integration on
      gene prioritization. In this paper, we aim at providing an extensive analysis of
      gene-disease associations not limited to genetic disorders, and a systematic
      comparison of different network integration methods for gene prioritization.
      MATERIALS AND METHODS: We collected nine different functional networks
      representing different functional relationships between genes, and we combined
      them through both unweighted and weighted network integration methods. We then
      prioritized genes with respect to each of the considered 708 medical subject
      headings (MeSH) diseases by applying classical guilt-by-association, random walk
      and random walk with restart algorithms, and the recently proposed kernelized
      score functions. RESULTS: The results obtained with classical random walk
      algorithms and the best single network achieved an average area under the curve
      (AUC) across the 708 MeSH diseases of about 0.82, while kernelized score
      functions and network integration boosted the average AUC to about 0.89. Weighted
      integration, by exploiting the different "informativeness" embedded in different
      functional networks, outperforms unweighted integration at 0.01 significance
      level, according to the Wilcoxon signed rank sum test. For each MeSH disease we
      provide the top-ranked unannotated candidate genes, available for further bio
      medical investigation. CONCLUSIONS: Network integration is necessary to boost the
      performances of gene prioritization methods. Moreover the methods based on
      kernelized score functions can further enhance disease gene ranking results, by
      adopting both local and global learning strategies, able to exploit the overall
      topology of the network.

PMID- 24726037
TI  - Bilateral eyelid retraction, loss of vision, ophthalmoplegia: an atypical triad
      in anti-GQ1b syndrome.

PMID- 24726038
TI  - [Sequential MRI imaging of progressive bilateral rostro-caudal medullary
      infarction].
AB  - Bilateral medial medullary infarction is exceptional. Initial symptoms can be
      misleading, even for a trained neurologist. We report two patients who presented
      progressive quadriplegia, anarthia and dysphagia. Sequential MRI showed
      progressive constitution of the characteristic "heart appearance" sign. 

PMID- 24726039
TI  - Rupture of a cerebellar arteriovenous malformation following thrombosis of the
      ipsilateral transverse sinus.

PMID- 24726040
TI  - [Cerebrovascular malformation revealed during the prethrombolysis workup in acute
      ischemic stroke. Impact on therapeutic decision making].
AB  - Intravenous recombinant tissue plasminogen activator for acute ischemic stroke is
      contraindicated in patients harboring an asymptomatic intracranial vascular
      malformation, whether it is incidentally discovered at the time of the initial
      cerebral imaging or previously known. Because thrombolysis is associated with a
      risk of serious intracerebral hemorrhage, it is theoretically possible that this
      treatment increases the risk of bleeding or rupture of these malformations.
      However, this risk seems very low in clinical practice. We report two cases, one
      with a probable brainstem cavernous malformation treated with alteplase for a
      supratentorial ischemic stroke who developed just after treatment a fatal
      brainstem hemorrhage, and another one with asymptomatic dural arteriovenous
      fistula, treated by endovascular thrombectomy solely. This approach was safe and
      effective, and the patient had an endovascular embolization of the fistula one
      month later as it became symptomatic. Based on the literature, we discuss the
      bleeding risk of asymptomatic intracranial vascular malformations in acute
      ischemic stroke patients treated with alteplase, depending on the type of
      malformation (intracranial aneurysm, arteriovenous and cavernous malformation or
      fistula), and the alternative therapeutic options. 

PMID- 24726041
TI  - [Post-dural (post-lumbar) puncture syndrome. Review and retrospective study at an
      emergency headache centre].
AB  - Post-lumbar puncture headache (PLPH) is a well-known syndrome resulting from
      spinal fluid leakage and delayed closure of a dural defect. The main symptom of
      PLPH is headache in upright posture relieved by lying down. Outcome is usually
      benign and complications are uncommon. The functional impact can however be
      important, leading to delayed discharge, sick leave and, if information delivery
      is ineffective, iterative consultations. Preventive measures have been published,
      but the prevalence of PLPH remains high (15 to 40% after diagnostic lumbar
      puncture). Needle size and type are probably the most important factors for
      reducing the risk of PLPH. Recovery can be rapid, within a few days. If PLPH
      persists after four days, an epidural blood patch should be discussed. The
      objective of this review is to summarize the literature on PLPH, and share the
      experience of our emergency headache center with an atraumatic 25-gauge needle
      (pencan, 0.5*90mm or 0.5*103mm, Braun, Germany). 

PMID- 24726043
TI  - Daylight-mediated photodynamic therapy in Spain: advantages and disadvantages.
AB  - Photodynamic therapy (PDT) is an option for the treatment of actinic keratosis,
      Bowen disease, and certain types of basal cell carcinoma. It is also used to
      treat various other types of skin condition, including inflammatory and
      infectious disorders. The main disadvantages of PDT are the time it takes to
      administer (both for the patient and for health professionals) and the pain
      associated with treatment. Daylight-mediated PDT has recently been reported to be
      an alternative to the conventional approach. Several studies have shown it to be
      similar in efficacy to and better tolerated than classic PDT for the treatment of
      mild to moderate actinic keratosis. Nevertheless, most of these studies are from
      northern Europe, and no data have been reported from southern Europe. The present
      article reviews the main studies published to date, presents the treatment
      protocol, and summarizes our experience with a group of treated patients. 

PMID- 24726042
TI  - [Seizures revealing phosphocalcic metabolism abnormalities].
AB  - Hypocalcemia due to hypoparathyroidism produces a broad spectrum of clinical
      manifestations, but overt symptoms may be sparse. One unusual presentation is
      onset or aggravation of epilepsy in adolescence revealing hypoparathyroidism.
      This situation can lead to delayed diagnosis, with inefficacity of the
      antiepileptic drugs. We report five cases of adolescence-onset epilepsy with
      unsuccessful antiepileptic therapy, even with gradually increasing dose. Physical
      examination revealed signs of hypocalcemia, confirmed biologically. Full testing
      disclosed the origin of the seizures: hypoparathyroidism in three patients and
      pseudohypoparathyroidism in the other two. In four of five patients, computed
      tomography showed calcification of the basal ganglia, defining Fahr's syndrome.
      The patients were treated with oral calcium and active vitamin D (1-alphahydroxy
      vitamin D3). Seizure frequency progressively decreased and serum calcium levels
      returned to normal. These cases illustrate the importance of the physical
      examination and of routine serum calcium assay in patients with new-onset
      epileptic seizures in order to detect hypocalcemia secondary to
      hypoparathyroidism. 

PMID- 24726044
TI  - Strategies for the early diagnosis of melanoma.

PMID- 24726045
TI  - Patterns of homoeologous gene expression shown by RNA sequencing in hexaploid
      bread wheat.
AB  - BACKGROUND: Bread wheat (Triticum aestivum) has a large, complex and hexaploid
      genome consisting of A, B and D homoeologous chromosome sets. Therefore each
      wheat gene potentially exists as a trio of A, B and D homoeoloci, each of which
      may contribute differentially to wheat phenotypes. We describe a novel approach
      combining wheat cytogenetic resources (chromosome substitution 'nullisomic
      tetrasomic' lines) with next generation deep sequencing of gene transcripts (RNA
      Seq), to directly and accurately identify homoeologue-specific single nucleotide
      variants and quantify the relative contribution of individual homoeoloci to gene
      expression. RESULTS: We discover, based on a sample comprising ~5-10% of the
      total wheat gene content, that at least 45% of wheat genes are expressed from all
      three distinct homoeoloci. Most of these genes show strikingly biased expression
      patterns in which expression is dominated by a single homoeolocus. The remaining
      ~55% of wheat genes are expressed from either one or two homoeoloci only, through
      a combination of extensive transcriptional silencing and homoeolocus loss.
      CONCLUSIONS: We conclude that wheat is tending towards functional diploidy,
      through a variety of mechanisms causing single homoeoloci to become the
      predominant source of gene transcripts. This discovery has profound consequences
      for wheat breeding and our understanding of wheat evolution.

PMID- 24726046
TI  - Setting the stage for chronic health problems: cumulative childhood adversity
      among homeless adults with mental illness in Vancouver, British Columbia.
AB  - BACKGROUND: It is well documented that childhood abuse, neglect and household
      dysfunction are disproportionately present in the backgrounds of homeless adults,
      and that these experiences adversely impact child development and a wide range of
      adult outcomes. However, few studies have examined the cumulative impact of
      adverse childhood experiences on homeless adults with mental illness. This study
      examines adverse events in childhood as predictors of duration of homelessness,
      psychiatric and substance use disorders, and physical health in a sample of
      homeless adults with mental illness. METHODS: This study was conducted using
      baseline data from a randomized controlled trial in Vancouver, British Columbia
      for participants who completed the Adverse Childhood Experiences (ACE) scale at
      18 months follow-up (n=364). Primary outcomes included current mental disorders;
      substance use including type, frequency and severity; physical health; duration
      of homelessness; and vocational functioning. RESULTS: In multivariable regression
      models, ACE total score independently predicted a range of mental health,
      physical health, and substance use problems, and marginally predicted duration of
      homelessness. CONCLUSIONS: Adverse childhood experiences are overrepresented
      among homeless adults with complex comorbidities and chronic homelessness. Our
      findings are consistent with a growing body of literature indicating that
      childhood traumas are potent risk factors for a number of adult health and
      psychiatric problems, particularly substance use problems. Results are discussed
      in the context of cumulative adversity and self-trauma theory. TRIALS
      REGISTRATION: This trial has been registered with the International Standard
      Randomized Control Trial Number Register and assigned ISRCTN42520374.

PMID- 24726048
TI  - Topiramate Augmentation in Resistant OCD: A Double-Blind Placebo-Controlled
      Clinical Trial.
AB  - OBJECTIVES: Glutaminergic dysfunction has been shown to be related to the
      pathphysiology of obsessive-compulsive disorder (OCD). Topiramate is an
      antiepileptic that inhibits glutaminergic action. The aim of this study is to
      evaluate the efficacy of topiramate augmentation in patients with treatment
      resistant OCD. METHODS: This augmentation trial was designed as a 12-week
      randomized, placebocontrolled, double-blind study. Forty-nine patients suffering
      from OCD who had failed to respond to at least 12 weeks of treatment of an
      adequate and stable dose of a selective serotonin reuptake inhibitor (SSRI) were
      randomly allocated to receive topiramate or placebo plus their current anti OCD
      treatment. Yale-Brown Obsessive Compulsive Scale (Y-BOCS) was the primary outcome
      measure. Treatment response was defined as 25 % or more decrease in scores of Y
      BOCS. The mean dosage of topiramate was 180.15 mg/day (range 100-200 mg/day).
      RESULTS: Forty-one patients (20 of 24 in topiramate group; 21 of 25 in placebo
      group) completed the trial. The topiramate group showed significant improvement
      over the study period (mean Y-BOCS score at week 12 as compared with baseline:
      P=.000). Those receiving topiramate experienced a mean decrease of 32.0% in Y
      BOCS score, compared with 2.4% decrease for those receiving placebo. Twelve
      patients in the topiramate group versus no patient in the placebo group were
      rated as responder. CONCLUSION: The results of our study demonstrated that
      topiramate may augment the therapeutic effect of SSRIs in treatment-resistant OCD
      patients. However, it should be noted that our study is preliminary and larger
      double-blind studies are needed to confirm these results.

PMID- 24726047
TI  - Prenatal exposure to antidepressants and language competence at age three:
      results from a large population-based pregnancy cohort in Norway.
AB  - OBJECTIVE: To examine the association between maternal use of selective serotonin
      reuptake inhibitors (SSRI) in pregnancy and language competence in their children
      at age three taking into account maternal symptoms of anxiety and depression.
      DESIGN: Population-based prospective pregnancy cohort study. SETTING: The
      Norwegian Mother and Child Cohort Study; recruited pregnant women from 1999
      through 2008. POPULATION: 45,266 women with 51,748 singleton pregnancies.
      METHODS: The association between short- or long-term use of SSRI during pregnancy
      and language competence in the child was investigated using multinomial logistic
      regression with three outcome categories: long, complicated sentences, fairly
      complete sentences and language delay. MAIN OUTCOME MEASURES: Children's language
      competence at age three measured by maternal report on a validated language
      grammar scale. RESULTS: Women reported use of SSRI in 386 (0.7%) pregnancies. Of
      these, 161 (42%) reported long-term use. Compared with children whose mothers
      took no SSRI, using the best language category as the reference, adjusted
      relative risk ratios (RRR) of having fairly complete sentences were 1.21 (95% CI
      0.85-1.72) and 2.28 (1.54-3.38) for short- and long-term SSRI use, respectively.
      The adjusted RRRs of language delay were 0.86 (0.42-1.76) and 2.30 (1.21-4.37).
      Symptoms of anxiety and depression in pregnancy were independently related to
      language delay, adjusted RRR 1.25 (1.03-1.50) and 1.83 (1.40-2.40) for short- and
      long-term symptoms, respectively. CONCLUSIONS: Prolonged use of SSRI during
      pregnancy was associated with lower language competence in children by age three
      independently of depression. Having symptoms of depression throughout pregnancy
      had an independent effect.

PMID- 24726049
TI  - Pharmaceutical modulation of the Renin Angiotensin aldosterone system for stroke
      prevention: a review of experimental and clinical evidence.
AB  - The renin angiotensin aldosterone system (RAAS) has been implicated in the
      pathogenesis of cerebrovascular diseases. During the past decades, AU: INCLUDE A
      NUMBER? RAAS has gained attention as an important therapeutic target in
      cardiovascular medicine. Modulation of the RAAS for primary and secondary stroke
      prevention seems an appealing strategy. Several experimental studies have showed
      that pre-treatment with RAAS inhibitors prior to the initiation of ischemia
      exerts favorable effects on infarct volume, brain edema, and cerebral blood flow
      in the marginal zone. Furthermore, the activation of angiotensin receptor type 2
      has been associated with neuroprotective effects. Accumulating evidence based on
      recent clinical trials indicate that blockade of RAAS has a potential role in
      stroke prevention. This review summarizes the pathophysiological aspects of brain
      RAAS and its constituents, presents experimental data on the neuroprotective
      actions of RAAS inhibitors and available evidence regarding their effects on
      stroke risk, and discuss future directions for research. 

PMID- 24726050
TI  - Recurrent concerns for child abuse: repeated consultations by a subspecialty
      child abuse team.
AB  - Physically abused children may be repeatedly reported to child protection
      services and undergo multiple medical evaluations. Less is known about recurrent
      evaluations by hospital-based child abuse teams for possible abuse. The
      objectives of this study were to determine the frequency of repeated
      consultations by child abuse teams and to describe this cohort in terms of injury
      pattern, perceived likelihood of abuse, disposition plan, and factors related to
      repeat consultation. This was a prospectively planned, secondary analysis of data
      from the Examining Siblings to Recognize Abuse (ExSTRA) research network.
      Subjects included children younger than 10 years of age who were referred to
      child abuse subspecialty teams at one of 20 U.S. academic centers. Repeat
      consultations occurred in 101 (3.5%; 95% CI 2.9-4.2%) of 2890 subjects. The
      incidence of death was 4% (95% CI 1-9%) in subjects with repeated consults and 3%
      (95% CI 2-3%) in subjects with single consults. Perceived likelihood of abuse
      from initial to repeat visit remained low in 33% of subjects, remained high in
      24.2% of subjects, went from low to high in 16.5%, and high to low in 26.4% of
      subjects. Themes identified among the subset of patients suspected of repeated
      abuse include return to the same environment, failure to comply with a safety
      plan, and abuse in foster care. Repeated consultation by child abuse specialists
      occurs for a minority of children. This group of children may be at higher risk
      of subsequent abuse and may represent an opportunity for quality improvement. 

PMID- 24726052
TI  - Sex differences in cardiac rehabilitation enrollment: a meta-analysis.
AB  - BACKGROUND: The present systematic review and meta-analysis examines studies
      published in the past 10 years that described cardiac rehabilitation (CR)
      enrollment among women and men, to determine whether a significant sex difference
      persists despite the evidence supporting the benefits of CR to women as well as
      men. METHODS: Scopus, MEDLINE, CINAHL, PsycINFO, PubMed, and The Cochrane Library
      databases were systematically searched for peer-reviewed articles published from
      July 2000 to July 2011. Titles and abstracts were screened, and the 623 selected
      full-text articles were independently screened based on predefined
      inclusion/exclusion criteria (guided by the Preferred Reporting Items for
      Systematic Reviews and Meta-Analyses; PRISMA) and assessed for quality using the
      Strengthening the Reporting of Observational studies in Epidemiology (STROBE)
      statement form. The meta-analysis was undertaken using Review Manager software.
      RESULTS: Twenty-six eligible observational studies reporting data for 297,719
      participants (128,499 [43.2%] women) were included. On average, 45.0% of men and
      38.5% of women enrolled in CR. In the pooled analysis, men were more likely to be
      enrolled in CR compared with women (female enrollment vs male enrollment odds
      ratio, 0.64; 95% confidence interval, 0.57-0.72; P < 0.00001). Heterogeneity was
      considered high (I(2) = 78%). In the subgroup analyses, systematic CR referral
      during inpatient tertiary care resulted in significantly greater enrollment among
      women than nonsystematic referral. CONCLUSIONS: Overall, rates of CR enrollment
      among women are significantly lower compared with men, with women being 36% less
      likely to enroll in a rehabilitation program.

PMID- 24726051
TI  - Zebrafish models for translational neuroscience research: from tank to bedside.
AB  - The zebrafish (Danio rerio) is emerging as a new important species for studying
      mechanisms of brain function and dysfunction. Focusing on selected central
      nervous system (CNS) disorders (brain cancer, epilepsy, and anxiety) and using
      them as examples, we discuss the value of zebrafish models in translational
      neuroscience. We further evaluate the contribution of zebrafish to neuroimaging,
      circuit level, and drug discovery research. Outlining the role of zebrafish in
      modeling a wide range of human brain disorders, we also summarize recent
      applications and existing challenges in this field. Finally, we emphasize the
      potential of zebrafish models in behavioral phenomics and high-throughput
      genetic/small molecule screening, which is critical for CNS drug discovery and
      identifying novel candidate genes. 

PMID- 24726053
TI  - Gestational diabetes and hypertensive disorders of pregnancy as vascular risk
      signals: an overview and grading of the evidence.
AB  - The occurrence of common pregnancy-related medical disorders identifies women at
      high risk of developing future vascular disease. Systematic reviews of cohort
      studies demonstrate that gestational diabetes confers a 7-fold risk increase for
      type 2 diabetes, and preeclampsia confers a 1.8-fold risk increase for type 2
      diabetes and 3.4-fold risk increase for hypertension. Gestational diabetes and
      hypertensive disorders of pregnancy (HDP) increase the risk of premature vascular
      disease, but the 2-fold risk increase associated with preeclampsia is only
      partially explained by the development of traditional vascular risk factors.
      Despite the compelling evidence for gestational diabetes and HDP as vascular risk
      indicators, there are no published Canadian vascular prevention guidelines that
      recognize these postpartum women. In contrast, the 2011 American Heart
      Association guidelines on cardiovascular disease in women include gestational
      diabetes and HDP in their vascular risk assessment. Studies indicate that the
      importance surveillance of vascular risk factors in these women after pregnancy
      is underappreciated by the women themselves and their physicians. Although a
      prudent diet and physically active lifestyle were demonstrated to reduce diabetes
      risk in women with a gestational diabetes history in the American Diabetes
      Prevention Program trial, adoption of these health behaviours is low; qualitative
      studies confirm a need for tailored strategies that address barriers and provide
      social support. Further research is also needed on approaches to reduce vascular
      risk in women with a history of gestational diabetes and HDP. Otherwise, an early
      window of opportunity for chronic disease prevention in young, high-risk women
      will be missed. 

PMID- 24726054
TI  - Constructing core competency indicators for clinical teachers in Taiwan: a
      qualitative analysis and an analytic hierarchy process.
AB  - BACKGROUND: The objective of this study was to construct a framework of core
      competency indicators of medical doctors who teach in the clinical setting in
      Taiwan and to evaluate the relative importance of the indicators among these
      clinical teachers. METHODS: The preliminary framework of the indicators was
      developed from an in-depth interview conducted with 12 clinical teachers who had
      previously been recognized and awarded for their teaching excellence in
      university hospitals. The framework was categorized into 4 dimensions: 1)
      Expertise (i.e., professional knowledge and skill); 2) Teaching Ability; 3)
      Attitudes and Traits; and 4) Beliefs and Values. These areas were further divided
      into 11 sub-dimensions and 40 indicators. Subsequently, a questionnaire built
      upon this qualitative analysis was distributed to another group of 17 clinical
      teachers. Saaty's eigenvector approach, or the so-called analytic hierarchy
      process (AHP), was applied to perform the pairwise comparisons between indicators
      and to determine the ranking and relative importance of the indicators. RESULTS:
      Fourteen questionnaires were deemed valid for AHP assessment due to completeness
      of data input. The relative contribution of the four main dimensions was 31% for
      Attitudes and Traits, 30% for Beliefs and Values, 22% for Expertise, and 17% for
      Teaching Ability. Specifically, 9 out of the 10 top-ranked indicators belonged to
      the "Attitudes and Traits" or "Beliefs and Values" dimensions, indicating that
      inner characteristics (i.e., attitudes, traits, beliefs, and values) were
      perceived as more important than surface ones (i.e., professional knowledge,
      skills, and teaching competency). CONCLUSION: We performed a qualitative analysis
      and developed a questionnaire based upon an interview with experienced clinical
      teachers in Taiwan, and used this tool to construct the key features for the role
      model. The application has also demonstrated the relative importance in the
      dimensions of the core competencies for clinical teachers in Taiwan.

PMID- 24726055
TI  - Afatinib use in non-small cell lung cancer previously sensitive to epidermal
      growth factor receptor inhibitors: the United Kingdom Named Patient Programme.
AB  - INTRODUCTION: Afatinib prolongs progression-free survival (PFS) in patients with
      non-small cell lung cancer (NSCLC) who were previously sensitive to erlotinib or
      gefitinib. This study investigated experience of afatinib under a Named Patient
      Use (NPU) programme. PATIENTS AND METHODS: Retrospective data for 63 patients
      were collected, including demographics, dose, toxicity and clinical efficacy.
      RESULTS: Response rate and median PFS were 14.3% and 2.6months, respectively.
      Diarrhoea and rash were the most common toxicities; 46% of patients required a
      dose reduction and 41% had a dose delay. CONCLUSIONS: Efficacy and safety in the
      NPU programme are consistent with the LUX-Lung 1 trial.

PMID- 24726056
TI  - Efficacy of anti-CD47 antibody-mediated phagocytosis with macrophages against
      primary effusion lymphoma.
AB  - BACKGROUND: Recently, the critical role of CD47 on the surface of resistant
      cancer cells has been proposed in their evasion of immunosurveillance. Primary
      effusion lymphoma (PEL) is a subtype of aggressive non-Hodgkin lymphoma that
      shows serous lymphomatous effusion in body cavities, especially in advanced
      acquired immunodeficiency syndrome (AIDS). PEL is resistant to conventional
      chemotherapy and has a poor prognosis. In this study, we evaluated the effect of
      anti-CD47 antibody (Ab) on PEL in vitro and in vivo. METHODS: Surface CD47 of PEL
      cell lines was examined by flow cytometry. Efficacy of knocking down CD47 or anti
      CD47 Ab-mediated phagocytosis against PEL was evaluated using mouse peritoneal
      macrophages and human macrophages in vitro. Primary PEL cells were injected
      intraperitoneally into NOD/Rag-2/Jak3 double-deficient (NRJ) mice to establish a
      direct xenograft mouse model. RESULTS: Surface CD47 of PEL cell lines was highly
      expressed. Knocking down CD47 and anti-CD47 Ab promoted phagocytic activities of
      macrophages in a CD47 expression-dependent manner in vitro. Treatment with anti
      CD47 Ab inhibited ascite formation and organ invasion completely in vivo compared
      with control IgG-treated mice. CONCLUSION: CD47 plays the pivotal role in the
      immune evasion of PEL cells in body cavities. Therapeutic antibody targeting of
      CD47 could be an effective therapy for PEL.

PMID- 24726057
TI  - Gene expression in fetal murine keratinocytes and fibroblasts.
AB  - BACKGROUND: Early fetuses heal wounds without the formation of a scar. Many
      studies have attempted to explain this remarkable phenomenon. However, the exact
      mechanism remains unknown. Herein, we examine the predominant cell types of the
      epidermis and dermis--the keratinocyte and fibroblast--during different stages of
      fetal development to better understand the changes that lead to scarring wound
      repair versus regeneration. MATERIALS AND METHODS: Keratinocytes and fibroblasts
      were harvested and cultured from the dorsal skin of time-dated BALB/c fetuses.
      Total RNA was isolated and microarray analysis was performed using chips with
      42,000 genes. Significance analysis of microarrays was used to select genes with
      >2-fold expression differences with a false discovery rate<2. Enrichment analysis
      was performed on significant genes to identify differentially expressed pathways.
      RESULTS: By comparing the gene expression profile of keratinocytes from E16
      versus E18 fetuses, we identified 24 genes that were downregulated at E16.
      Analysis of E16 and E18 fibroblasts revealed 522 differentially expressed genes.
      Enrichment analysis showed the top 20 signaling pathways that were downregulated
      in E16 keratinocytes and upregulated or downregulated in E16 fibroblasts.
      CONCLUSIONS: Our data reveal 546 differentially expressed genes in keratinocytes
      and fibroblasts between the scarless and scarring transition. In addition, a
      total of 60 signaling pathways have been identified to be either upregulated or
      downregulated in these cell types. The genes and pathways recognized by our study
      may prove to be essential targets that may discriminate between fetal wound
      regeneration and adult wound repair.

PMID- 24726058
TI  - Impact of podiatry resident experience level in hallux valgus surgery on
      postoperative outcomes.
AB  - BACKGROUND: Despite modern advancements in transosseous fixation and operative
      technique, hallux valgus (i.e., bunion) surgery is still associated with a higher
      than usual amount of patient dissatisfaction and is generally recognized as a
      complex and nuanced procedure requiring precise osseous and capsulotendon
      balancing. It stands to reason then that familiarity and skill level of trainee
      surgeons might impact surgical outcomes in this surgery. The aim of this study
      was to determine whether podiatry resident experience level influences midterm
      outcomes in hallux valgus surgery (HVS). METHODS: Consecutive adults who
      underwent isolated HVS via distal metatarsal osteotomy at a single US
      metropolitan teaching hospital from January 2004 to January 2009 were contacted
      and asked to complete a validated outcome measure of foot health (Manchester
      Oxford Foot Questionnaire) regarding their operated foot. Resident experience
      level was quantified using the surgical logs for the primary resident of record
      at the time of each case. Associations were assessed using linear and logistic
      regression analyses. RESULTS: A total of 102 adult patients (n = 102 feet) agreed
      to participate with a mean age of 46.8 years (standard deviation 13.1, range 18
      71) and average length of follow-up 6.2 y (standard deviation 1.4, range 3.6
      8.6). Level of trainee experience was not associated with postoperative outcomes
      in either the univariate (odds ratio 0.99 [95% confidence interval, 0.98-1.01], P
      = 0.827) or multivariate analyses (odds ratio 1.00 [95% confidence interval, 0.97
      1.02], P = 0.907). CONCLUSIONS: We conclude that podiatry resident level of
      experience in HVS does not contribute appreciably to postoperative clinical
      outcomes.

PMID- 24726059
TI  - In vivo application of tissue-engineered blood vessels of bacterial cellulose as
      small arterial substitutes: proof of concept?
AB  - BACKGROUND: Tissue-engineered blood vessels (TEBVs) represent an innovative
      approach for overcoming reconstructive problems associated with vascular diseases
      by providing small-caliber vascular grafts. This study aimed to evaluate a novel
      biomaterial of bacterially synthesized cellulose (BC) as a potential scaffold for
      small-diameter TEBV. METHODS: Small-diameter blood vessels with a supramolecular
      fiber network structure consisting of tubular hydrogels from biodesigned
      cellulose were created using Gluconacetobacter strains and Matrix reservoir
      technology. BC tubes (length: 100 mm, inner diameter: 4.0-5.0 mm) were applied to
      replace the carotid arteries of 10 sheep for a period of 3 mo to gain further
      insights into (a) functional (in vivo) performance, (b) ability of providing a
      scaffold for the neoformation of a vascular wall and (c) their proinflammatory
      potential, and the (d) technical feasibility of the procedure. RESULTS:
      Preoperative analysis revealed a bursting strength of the grafts of approximately
      800 mm Hg and suture retention strength of 4-5 N. Postexplantation analysis
      showed a patency rate of 50% (n = 5) and physiological performance of the patent
      grafts at 4, 8, and 12 wk postoperatively, compared with native arteries.
      Histologic analysis revealed a neoformation of a vascular wall-like structure
      along the BC scaffold consisting of immigrated vascular smooth muscle cells and a
      homogeneous endothelialization of the inner graft surface without signs of
      prothrombogenic or inflammatory potential. Scanning electron microscopy revealed
      a confluent luminal endothelial cell layer and the immigration of vascular smooth
      muscle cells into the BC matrix. CONCLUSIONS: BC grafts provide a scaffold for
      the neoformation of a three-layered vascular wall exhibit attractive properties
      for their use in future TEBV programs for cardiovascular surgery.

PMID- 24726060
TI  - Osthole prevents intestinal ischemia-reperfusion-induced lung injury in a rodent
      model.
AB  - BACKGROUND: Intestinal ischemia-reperfusion (II/R) is associated with high
      morbidity and mortality. The aim of this study was to investigate the effects of
      osthole on lung injury and mortality induced by II/R. METHODS: A rat model of
      II/R was induced by clamping the superior mesenteric artery for 90 min followed
      by reperfusion for 240 min. Osthole was administrated intraperitoneally at 30 min
      before intestinal ischemia (10 or 50 mg/kg). The survival rate and mean arterial
      pressure were observed. Blood samples were obtained for blood gas analyses. Lung
      injury was assessed by the histopathologic changes (hematoxylin and eosin
      staining), lung wet-to-dry weight ratio, and pulmonary permeability index. The
      levels of reactive oxygen species, malondialdehyde, interleukin 6, and tumor
      necrosis factor alpha, as well as the activities of superoxide dismutase and
      myeloperoxidase in lung were measured. RESULTS: The survival rate, ratio of
      arterial oxygen tension to fraction of inspired oxygen, and mean arterial
      pressure decreased significantly after II/R. Results also indicated that II/R
      induced severe lung injury evidenced by increase in pathologic scores, lung wet
      to-dry weight ratio, and pulmonary permeability index, which was accompanied by
      increases in the levels of pulmonary reactive oxygen species, malondialdehyde,
      interleukin 6, tumor necrosis factor alpha, and the pulmonary myeloperoxidase
      activity and a decrease in superoxide dismutase activity. Osthole could
      significantly ameliorate lung injury and improve the previously mentioned
      variables. CONCLUSIONS: These findings indicated that osthole could attenuate the
      lung injury induced by II/R in rats, at least in part, by inhibiting inflammatory
      response and oxidative stress.

PMID- 24726061
TI  - Monocyte activity is linked with abdominal aortic aneurysm diameter.
AB  - BACKGROUND: Systemic inflammation and increased matrix metalloproteinase (MMP)
      cause elastin degradation leading to abdominal aortic aneurysm (AAA) expansion.
      Several prospective studies report that statin therapy can reduce AAA expansion
      through anti-inflammation. We hypothesize that monocyte activity plays a pivotal
      role in this AAA development and this study examines patient peripheral blood
      monocyte cell adhesion, transendothelial migration, and MMP concentrations
      between AAA and non-AAA patients. MATERIALS AND METHODS: Peripheral blood was
      collected and monocytes isolated from control (n=15) and AAA (n=13) patients.
      Monocyte adhesion, transmigration, and permeability assays were assessed. Luminex
      assays determined MMP-9 and tissue inhibitor of metalloproteinase-4 (TIMP-4)
      concentrations from cell culture supernatant and patient serum. RESULTS: AAA
      patient monocytes showed increased adhesion to the endothelium relative
      fluorescence units (RFU, 0.33+/-0.17) versus controls (RFU, 0.13+/-0.04;
      P=0.005). Monocyte transmigration was also increased in AAA patients (RFU, 0.33+/
      0.11) compared with controls (RFU, 0.25+/-0.04, P=0.01). Greater numbers of
      adhesive (R2=0.66) and transmigratory (R2=0.86) monocytes were directly
      proportional to the AAA diameter. Significantly higher serum levels of MMP-9
      (2149.14+/-947 pg/mL) were found in AAA patients compared with controls (1189.2+/
      293; P=0.01). TIMP-4 concentrations were significantly lower in AAA patients
      (826.7+/-100 pg/mL) compared with controls (1233+/-222 pg/mL; P=0.02). Cell
      culture supernatant concentrations of MMP and TIMP from cocultures were higher
      than monocyte-only cultures. CONCLUSIONS: Monocytes from AAA patients have
      greater adhesion and transmigration through the endothelium in vitro, leading to
      elevated MMP-9 levels and the appropriate decrease in TIMP-4 levels. The ability
      to modulate monocyte activity may lead to novel medical therapies to decrease AAA
      expansion.

PMID- 24726062
TI  - Lipopolysaccharide-mediated enhancement of zymosan phagocytosis by RAW 264.7
      macrophages is independent of opsonins, laminarin, mannan, and complement
      receptor 3.
AB  - BACKGROUND: Fungal and bacterial coinfections are common in surgical settings;
      however, little is known about the effects of polymicrobial interactions on the
      cellular mechanisms involved in innate immune recognition and phagocytosis.
      MATERIALS AND METHODS: Zymosan particles, cell wall derivatives of the yeast
      Saccharomyces cerevisiae, are used to model fungal interactions with host immune
      cells since they display carbohydrates, including beta-glucan, that are
      characteristic of fungal pathogens. Using in vitro cell culture, RAW 264.7
      macrophages were challenged with zymosan, and phagocytosis determined via light
      microscopy. The effects of different concentrations of lipopolysaccharide (LPS)
      on zymosan phagocytosis were assessed. In addition, the transfer of supernatant
      from LPS-treated cells to naive cells, the effects of soluble carbohydrates
      laminarin, mannan, or galactomannan, and the impact of complement receptor 3
      (CR3) inhibition on phagocytosis were also determined. RESULTS: LPS enhanced
      phagocytosis of zymosan in a dose-dependent manner. Transfer of supernatants from
      LPS-primed cells to naive cells had no effect on phagocytosis. Laminarin
      inhibited zymosan phagocytosis in naive cells but not in LPS-primed cells.
      Neither mannan, galactomannan, nor CR3 inhibition had a significant effect on
      ingestion of unopsonized zymosan in naive or LPS-treated cells. CONCLUSIONS:
      Zymosan recognition by naive cells is inhibited by laminarin, but not mannan,
      galactomannan, or CR3 inhibition. LPS enhancement of phagocytosis is laminarin
      insensitive and not mediated by supernatant factors or zymosan engagement by the
      mannose or CR3 receptors. Our data suggest alternative mechanisms of zymosan
      recognition in the presence and absence of LPS.

PMID- 24726063
TI  - TERT promoter hotspot mutations are recurrent in myxoid liposarcomas but rare in
      other soft tissue sarcoma entities.
AB  - BACKGROUND: Recently, recurrent point mutations in the telomerase reverse
      transcriptase (TERT) promoter region have been found in many human cancers,
      leading to a new transcription factor binding site, increased induction of TERT
      and subsequently to telomere maintenance. We determined the prevalence of TERT
      promoter mutations in soft tissue sarcomas of 341 patients comprising 16 entities
      and in 16 sarcoma cell lines covering 7 different soft tissue sarcoma types.
      METHODS: The sarcoma tissue samples were collected from the archives of the
      Institute of Pathology, University of Heidelberg and were composed of 39 myxoid
      liposarcomas (MLS), 61 dedifferentiated liposarcomas, 15 pleomorphic
      liposarcomas, 27 leiomyosarcomas, 25 synovial sarcomas (SS), 35 malignant
      peripheral nerve sheath tumors (MPNST), 40 undifferentiated pleomorphic sarcomas,
      17 myxofibrosarcomas, 9 low grade fibromyxoid sarcomas, 10 cases of
      dermatofibrosarcoma protuberans, 31 solitary fibrous tumors (SFT), 8
      extraskeletal myxoid chondrosarcomas, 9 angiosarcomas, 6 alveolar soft part
      sarcomas, 5 clear cell sarcomas and 4 epithelioid sarcomas. Sarcoma cell lines
      were obtained from the raising laboratories. A 193 bp fragment of the TERT
      promoter region covering the hot-spot mutations C228T and C250T was amplified,
      and direct sequencing of the PCR products was performed. RESULTS: TERT promoter
      mutations were detected in 36/341 sarcomas. They were highly recurrent in MLS
      (29/39; 74%) and were in the present MLS series not associated with the phenotype
      (myxoid vs. round cell variant), tumor grade, tumor site and patients' median age
      or gender. In the remaining cases, TERT promoter mutations were found only in
      7/302 sarcoma samples and confined to SFTs (4/31; 13%), MPNSTs (2/35; 6%), and
      SSs (1/25; 4%). Within the collection of sarcoma cell lines examined, TERT
      promoter mutations were detected in two MLS and in one of three MPNST cell lines.
      CONCLUSIONS: TERT promoter mutations are frequent in MLSs including their round
      cell variants, representing the most prevalent mutation identified in this
      sarcoma entity to date, and in a minor fraction of SFTs, MPNSTs and SSs. The
      majority of sarcomas are devoid of TERT promoter hotspot mutations. These data
      suggest that telomere maintenance through increased expression of telomerase
      plays an important role in the pathogenesis especially of MLS.

PMID- 24726064
TI  - Clinicopathological significance of PI3K, Akt and survivin expression in gastric
      cancer.
AB  - BACKGROUND: Gastric cancer is the second leading cause of cancer-related deaths
      worldwide, and is characterized by invasion and metastasis. Increasing attention
      is being focused on discovering molecular markers for diagnosis and prognosis.
      Our objective was to evaluate PI3K, Akt and survivin protein expression in
      gastric cancer, and their correlations with clinicohistological features and
      prognosis in patients with gastric cancer. METHODS: Tissue samples were obtained
      from 70 patients with gastric cancer patients and 20 patients with normal gastric
      mucosa. The protein levels of PI3K, Akt and survivin were evaluated by
      immunohistochemistry. Statistical analyses were performed to establish the
      correlations between their expressions and patients' clinicopathologic
      characteristics. RESULTS: The positive expression rates of PI3K, Akt and survivin
      were significantly higher in the gastric cancer tissues compared to normal
      gastric mucosa (P<0.05). Expression levels of PI3K, Akt and survivin proteins
      were significantly correlated with TNM stage, differentiation grade, lymph node
      metastasis and metastases to other organs (P<0.05). Cooperative relationships
      were identified between PI3K and Akt, and PI3K and survivin (P<0.01), suggesting
      the involvement of the PI3K/Akt/survivin signaling pathway in the tumorigenesis
      of gastric cancer. CONCLUSIONS: Protein expression of PI3K, Akt and survivin were
      significantly associated with the development, progression and metastasis of
      gastric cancer and may have value as diagnostic and prognostic markers in gastric
      cancer.

PMID- 24726065
TI  - A systematic analysis of predicted MiR-31-targets identifies a diagnostic and
      prognostic signature for lung cancer.
AB  - INTRODUCTION: Recent studies have shown that miR-31 could play a potential role
      as diagnostic and prognostic biomarkers of several cancers including lung cancer.
      The aim of this study is to globally summarize the predicting targets of miR-31
      and their potential function, pathways and networks, which are involved in the
      biological behavior of lung cancer. METHODS: We have conducted the natural
      language processing (NLP) analysis to identify lung cancer-related molecules in
      our previous work. In this study, miR-31 targets predicted by combinational
      computational methods. All target genes were characterized by gene ontology (GO),
      pathway and network analysis. In addition, miR-31 targets analysis were
      integrated with the results from NLP analysis, followed by hub genes interaction
      analysis. RESULT: We identified 27 hub genes by the final integrative analysis
      and suggested that miR-31 may be involved in the initiation, progression and
      treatment response of lung cancer through cell cycle, cytochrome P450 pathway,
      metabolic pathways, apoptosis, chemokine signaling pathway, MAPK signaling
      pathway, as well as others. CONCLUSION: Our data may help researchers to predict
      the molecular mechanisms of miR-31 in the molecular mechanism of lung cancer
      comprehensively. Moreover, the present data indicate that the interaction of miR
      31 targets may be promising candidates as biomarkers for the diagnosis, prognosis
      and personalized therapy of lung cancer.

PMID- 24726066
TI  - Efficacy of occupational therapy for patients with Parkinson's disease: a
      randomised controlled trial.
AB  - BACKGROUND: There is insufficient evidence to support use of occupational therapy
      interventions for patients with Parkinson's disease. We aimed to assess the
      efficacy of occupational therapy in improving daily activities of patients with
      Parkinson's disease. METHODS: We did a multicentre, assessor-masked, randomised
      controlled clinical trial in ten hospitals in nine Dutch regional networks of
      specialised health-care professionals (ParkinsonNet), with assessment at 3 months
      and 6 months. Patients with Parkinson's disease with self-reported difficulties
      in daily activities were included, along with their primary caregivers. Patients
      were randomly assigned (2:1) to the intervention or control group by a computer
      generated minimisation algorithm. The intervention consisted of 10 weeks of home
      based occupational therapy according to national practice guidelines; control
      individuals received usual care with no occupational therapy. The primary outcome
      was self-perceived performance in daily activities at 3 months, assessed with the
      Canadian Occupational Performance Measure (score 1-10). Data were analysed using
      linear mixed models for repeated measures (intention-to-treat principle).
      Assessors monitored safety by asking patients about any unusual health events
      during the preceding 3 months. This trial is registered with ClinicalTrials.gov,
      NCT01336127. FINDINGS: Between April 14, 2011, and Nov 2, 2012, 191 patients were
      randomly assigned to the intervention group (n=124) or the control group (n=67).
      117 (94%) of 124 patients in the intervention group and 63 (94%) of 67 in the
      control group had a participating caregiver. At baseline, the median score on the
      Canadian Occupational Performance Measure was 4.3 (IQR 3.5-5.0) in the
      intervention group and 4.4 (3.8-5.0) in the control group. At 3 months, these
      scores were 5.8 (5.0-6.4) and 4.6 (4.6-6.6), respectively. The adjusted mean
      difference in score between groups at 3 months was in favour of the intervention
      group (1.2; 95% CI 0.8-1.6; p<0.0001). There were no adverse events associated
      with the study. INTERPRETATION: Home-based, individualised occupational therapy
      led to an improvement in self-perceived performance in daily activities in
      patients with Parkinson's disease. Further work should identify which factors
      related to the patient, environmental context, or therapist might predict which
      patients are most likely to benefit from occupational therapy. FUNDING: Prinses
      Beatrix Spierfonds and Parkinson Vereniging.

PMID- 24726067
TI  - Occupational therapy for Parkinson's disease: increasing awareness.

PMID- 24726068
TI  - Cognitive aspects of motor control.

PMID- 24726069
TI  - da Vinci revisited: building momentum for action.

PMID- 24726070
TI  - Examining the role of amenable mortality as an indicator of health system
      effectiveness.
AB  - A recent paper in this journal raised questions as to the reliability,
      sensitivity and validity of amenable mortality as an indicator of health system
      effectiveness. In this commentary, we revisit the evidence that was put forward,
      and suggest that there are several good reasons for assessing health system
      effectiveness on the basis of amenable mortality. moreover, provided multiple
      years of data are used to increase the precision of measurement of amenable
      mortality rates in very small regions, this indicator of health system
      effectiveness can be considered a valuable tool for research and performance
      measurement. 

PMID- 24726071
TI  - Strategically investing in health research: the little-big program called RPP.
AB  - The Regional Partnerships Program (RPP) was a program of the Canadian Institutes
      of Health Research (CIHR) and six provinces - Saskatchewan, Manitoba, New
      Brunswick, Nova Scotia, Prince Edward Island, and Newfoundland and Labrador. CIHR
      and each province contributed 50% to support health research that was recommended
      for funding by peer review but fell below the CIHR budgetary cut-off for funding.
      The provinces would like to commend CIHR for this strategic initiative and
      highlight the impact that small investment like RPP has had on engaging these
      provinces in the health research enterprise and expanding health research and its
      benefits across the country. 

PMID- 24726072
TI  - Communities of practice as a professional and organizational development strategy
      in local public health organizations in Quebec, Canada: an evaluation model.
AB  - Communities of practice (CoPs) are among the professional development strategies
      most widely used in such fields as management and education. Though the approach
      has elicited keen interest, knowledge pertaining to its conceptual underpinnings
      is still limited, thus hindering proper assessment of CoPs' effects and the
      processes generating the latter. To address this shortcoming, this paper presents
      a conceptual model that was developed to evaluate an initiative based on a CoP
      strategy: Health Promotion Laboratories are a professional development
      intervention that was implemented in local public health organizations in
      Montreal (Quebec, Canada). The model is based on latest theories on work-group
      effectiveness and organizational learning and can be usefully adopted by
      evaluators who are increasingly called upon to illuminate decision-making about
      CoPs. Ultimately, validation of this conceptual model will help advance knowledge
      and practice pertaining to CoPs as well as professional and organizational
      development strategies in public health. 

PMID- 24726073
TI  - The team climate inventory as a measure of primary care teams' processes:
      validation of the French version.
AB  - PURPOSE: Evaluate the psychometric properties of the French version of the short
      19-item Team Climate Inventory (TCI) and explore the contributions of individual
      and organizational characteristics to perceived team effectiveness. METHOD: The
      TCI was completed by 471 of the 618 (76.2%) healthcare professionals and
      administrative staff working in a random sample of 37 primary care practices in
      the province of Quebec. RESULTS: Exploratory factor analysis confirmed the
      original four-factor model. Cronbach's alphas were excellent (from 0.88 to 0.93).
      Latent class analysis revealed three-class response structure. Respondents in
      practices with professional governance had a higher probability of belonging to
      the "High TCI" class than did practices with community governance (36.7% vs.
      19.1%). Administrative staff tended to fall into the "Suboptimal TCI" class more
      frequently than did physicians (36.5% vs. 19.0%). CONCLUSION: Results confirm the
      validity of our French version of the short TCI. The association between
      professional governance and better team climate merits further exploration.

PMID- 24726074
TI  - Patients' perceptions of joint replacement care in a changing healthcare system:
      a qualitative study.
AB  - BACKGROUND: Ontario has introduced strategies over the past decade to reduce wait
      times and length of stay and improve access to physiotherapy for orthopaedic and
      other patients. The aim of this study is to explore patients' experiences of
      joint replacement care during a significant system change in their care setting.
      METHODS: A secondary analysis was done on semi-structured qualitative interviews
      that were conducted in 2009 with 12 individuals who had undergone at least two
      hip or knee replacements five years apart at a specialized orthopaedic centre in
      Ontario, Canada. Interview transcripts were coded and then organized into themes.
      RESULTS: Although the original study aimed to capture participants' experiences
      with changes in anaesthetic technique between their first and second joint
      replacements, the participants described several unrelated differences in the
      care they received during this period. For example, participants had difficulty
      obtaining a referral to an orthopaedic surgeon from their family physician. They
      also noted that the hospital stay and in-hospital physiotherapy they received
      were shorter after the second joint replacement surgery. They identified guidance
      from physiotherapists as an important component of their recovery, but sometimes
      had difficulty arranging physiotherapy after hospital discharge following their
      most recent surgery. CONCLUSIONS: The changes described between the first and
      second joint replacements provide the participants' perspective on the impact of
      policy changes on wait times, reduced lengths of hospital stay and physiotherapy
      access. The impact of these policy changes, often made in an attempt to improve
      access to care, had an unintended and detrimental effect on participants'
      perceptions and experiences of the quality of care provided.

PMID- 24726075
TI  - Predicting patients with high risk of becoming high-cost healthcare users in
      Ontario (Canada).
AB  - Literature and original analysis of healthcare costs have shown that a small
      proportion of patients consume the majority of healthcare resources. A proactive
      approach is to target interventions towards those patients who are at risk of
      becoming high-cost users (HCUs). This approach requires identifying high-risk
      patients accurately before substantial avoidable costs have been incurred and
      health status has deteriorated further. We developed a predictive model to
      identify patients at risk of becoming HCUs in Ontario. HCUs were defined as the
      top 5% of patients incurring the highest costs. Information was collected on
      various demographic and utilization characteristics. The modelling technique used
      was logistic regression. If the top 5% of patients at risk of becoming HCUs are
      followed, the sensitivity is 42.2% and specificity is 97%. Alternatives for
      implementation of the model include collaboration between different levels of
      healthcare services for personalized healthcare interventions and interventions
      addressing needs of patient cohorts with high-cost conditions. 

PMID- 24726076
TI  - Provincial disparities of growth hormone coverage for young adult survivors of
      paediatric brain tumours across Canada.
AB  - BACKGROUND: Young adult survivors of paediatric brain tumours (PBTs) who have
      been treated with radiation therapy will likely be severely growth hormone
      deficient when retested at the achievement of final height. Growth hormone
      replacement therapy (GHRT) is administered to treat growth hormone deficiency
      (GHD). Public drug coverage for GHRT falls under the responsibility of provincial
      governments across Canada. This study sought to determine the extent of public
      drug coverage and cost in each Canadian province for GHRT to treat GHD during
      adulthood for young adult survivors of PBTs. METHODS: Data were collected from
      provincial government resources and drug formularies from 2012-2013 on the extent
      of coverage for GHRT based on a clinical case scenario representative of a young
      adult survivor of a PBT with childhood-onset radiation-induced GHD, the
      ingredient cost for GHRT and the applicable provincial public drug plan cost
      sharing policies. A model was then created to simulate out-of-pocket costs
      incurred by a young adult male and a young adult female survivor of a PBT for one
      year of GHRT in each province with applicable cost-sharing arrangements and
      levels of low annual individual total income that best represent the majority of
      young adult survivors of PBTs. Out-of-pocket costs were expressed as a percentage
      of annual income. Comparisons were made between provinces descriptively, and
      variation among provinces was summarized statistically. RESULTS: Alberta,
      Manitoba, Ontario, Quebec, New Brunswick, and Newfoundland and Labrador provide
      coverage for GHD during adulthood on a case-by-case basis, while British
      Columbia, Saskatchewan, Nova Scotia and Prince Edward Island provide no coverage.
      The percentage of annual income to fund GHRT across the provinces without public
      coverage ranged from 14.4% to 25.5% for males and 21.5% to 38.3% for females, and
      with public coverage was 0.0% to 4.1% for males and 0.0% to 5.0% for females.
      INTERPRETATION: There are considerable out-of-pocket costs and variation in
      coverage provided by provincial public drug plans to fund GHRT for young adult
      survivors of PBTs with GHD. The implementation of a national drug formulary could
      potentially prevent undue financial hardship and remove disparities resulting
      from variations in provincial drug plans.

PMID- 24726077
TI  - Avian chlamydiosis: two more bacterial players discovered.

PMID- 24726079
TI  - Foreword.

PMID- 24726078
TI  - Characterisation of Streptococcus suis isolates from wild boars (Sus scrofa).
AB  - Wild boar are widely distributed throughout the Iberian Peninsula and can carry
      potentially virulent strains of Streptococcus suis. The objective of this study
      was to determine the prevalence of S. suis in wild boars from two large
      geographical regions of Spain. Serotypes 1, 2, 7 and 9 identified were further
      genetically characterised by virulence-associated genotyping, pulsed-field gel
      electrophoresis (PFGE) and multilocus sequence typing (MLST) to determine the
      population structure of S. suis carried by these animals. Streptococcus suis was
      isolated from 39.1% of the wild boars examined: serotype 9 was the most
      frequently isolated (12.5%), followed by serotype 1 (2.5%). Serotype 2 was rarely
      isolated (0.3%). Eighteen additional serotypes were identified indicating wide
      diversity of this pathogen within the wild boar population. This heterogeneity
      was confirmed by PFGE and MLST analyses and the majority of isolates exhibited
      the virulence-associated genotype mrp-/epf-/sly-. The results of this study
      highlight that the carriage of S. suis by wild boars is commonplace. However,
      MLST data indicate that these isolates are not related to prevalent clonal
      complexes ST1, ST16, ST61 and ST87 typically associated with infection of pigs or
      humans in Europe.

PMID- 24726080
TI  - Gender and health disparities: the case of male gender.

PMID- 24726081
TI  - An argument for male gender as a root cause or fundamental social determinant of
      health.

PMID- 24726082
TI  - A review of the current epidemiology and treatment options for prostate cancer.

PMID- 24726083
TI  - Men and suicide in primary care.

PMID- 24726084
TI  - Profile of Behavior and IQ in Anemic Children.
AB  - OBJECTIVES: Study the profile of behavior and intelligence of children with
      anemia and their possible association to the hematological parameters. METHODS:
      Fifty-eight children (42 anemic; 16 controls), matched by age, sex, and culture
      with the patients, were subjected to both behavioral and IQ testing using Revised
      Behavior Problem Checklist (RBPCL) and Wechsler intelligence scale for children
      revised and hematological laboratory evaluation RESULTS: After controlling for
      age, sex and culture, the mean IQ was lower in the iron deficiency group than
      both thalassemic and control groups (P<.000). The mean scores of conduct
      disorder, socialized aggression, and anxiety withdrawal of RBPCL were higher in
      thalassemic group while the mean scores of motor excess and attention problems
      score were higher in the iron deficiency group. Regression analysis showed that
      hemoglobin concentration in gram/dl was the predictor of IQ in both anemic group
      and for attention problems in iron deficiency group while the mean corpuscular
      volume was the predictor of motor excess score in iron deficiency group. Other
      associations were not statistically significant. CONCLUSION: Behavior problems
      and low intelligence were significantly high among anemic children. Their
      association with the hematological parameters varies according to the type of
      behavior and the type of anemia. These results cannot exclude the role of other
      factors in shaping the profile of behavior and IQ.

PMID- 24726085
TI  - A novel immunodeficiency syndrome as a rare cause of secondary pulmonary alveolar
      proteinosis: a diagnosis after 5 decades.
AB  - Case report of a male patient with a five-decade follow-up history in a tertiary
      care hospital distinguished for malabsorption syndrome, failure-to-thrive,
      meningitis and recurrent bacterial, fungal and mycobacterial pulmonary
      infections. Additionally, he developed epidermodysplasia verruciformis, several
      in situ spinocellular carcinomas and an uncharacteristic parenchymal lung
      disease. Surgical lung biopsy suggested pulmonary alveolar proteinosis with
      fibrotic change. Retrospectively, severe monocytopenia had been overlooked in the
      past, as well as low B and NK cell blood counts. Flow cytometry confirmed the
      absence of the previous cell subsets along with an undetectable population of
      dendritic blood cells. Dendritic cell, monocyte, B and NK lymphoid Human
      Deficiency Syndrome (DCMLS) is a novel rare immunodeficiency described in 2010,
      linked to GATA-2 mutation. This syndrome should be highlighted as a rare cause of
      acquired PAP, with a radiological pattern encompassing potential fibrotic change.
      Failure to recognize monocytopenia may impede the chance to diagnose. 

PMID- 24726087
TI  - Trial design for breakthrough pain: is it ethical to have a placebo in a trial?
      Author reply.

PMID- 24726086
TI  - Audit of the use of intravenous immunoglobulin for antibody deficiencies in a
      Clinical Immunology Unit.

PMID- 24726088
TI  - Effect of ketoconazole on the pharmacokinetics of the dipeptidyl peptidase-4
      inhibitor teneligliptin: an open-label study in healthy white subjects in
      Germany.
AB  - OBJECTIVE: The aim of this study was to examine the effect of ketoconazole, a
      potent cytochrome P450 (CYP) 3A4 and P-glycoprotein (P-gp) inhibitor, on
      teneligliptin pharmacokinetics and to evaluate the safety of combined
      administration of teneligliptin with ketoconazole. METHODS: This open-label,
      fixed-sequence study was conducted in 16 healthy adult volunteers in Germany. On
      day 1, under fasting conditions, 20 mg of teneligliptin was administered to
      evaluate the pharmacokinetics of teneligliptin alone. For 3 days (days 8-10), 400
      mg of ketoconazole was administered once daily. On day 11, teneligliptin 20 mg
      and ketoconazole 400 mg were concurrently administered, and for 2 days (days 12
      and 13), ketoconazole was administered once daily. The pharmacokinetic parameters
      (Cmax, Tmax, AUC, terminal t1/2, apparent total plasma clearance, and Vd during
      the terminal phase) of teneligliptin on days 1 and 11 were calculated. The safety
      profile was evaluated based on adverse events and clinical findings. To
      investigate the role of human P-gp in membrane permeation of teneligliptin, an in
      vitro study was performed to measure the transcellular transport of teneligliptin
      across monolayers of human P-gp-expressing cells and control cells. RESULTS: For
      Cmax and AUC, the geometric least squares mean ratios (90% CIs) of teneligliptin
      with ketoconazole to teneligliptin alone were 1.37 (1.25-1.50) and 1.49 (1.39
      1.60), respectively. There was no change in t1/2 of the terminal elimination
      phase. In addition, the tolerability of teneligliptin coadministered with
      ketoconazole was acceptable. The in vitro study revealed corrected efflux ratios
      for teneligliptin of 6.81 and 5.27 at teneligliptin concentrations of 1 and 10
      MUM, respectively. CONCLUSIONS: Because the exposure to teneligliptin in combined
      administration with ketoconazole, a potent CYP3A4 and P-gp inhibitor, was less
      than twice that of administration of teneligliptin alone, it is suggested that
      combined administration of teneligliptin with drugs and foods that inhibit CYP3A4
      should not cause a marked increase in exposure. The results of our in vitro study
      suggest that teneligliptin is a substrate of P-gp. CLINICAL TRIAL REGISTRATION:
      EudraCT No. 2009-016652-51.

PMID- 24726089
TI  - Trial design for breakthrough pain: is it ethical to have a placebo in a trial?

PMID- 24726090
TI  - Effects of an angiotensin II type 1 receptor blocker on aortic valve sclerosis in
      a preclinical model.
AB  - BACKGROUND: Aortic valve sclerosis (AVS) is a chronic progressive disease
      involving lipid infiltration, inflammation, and tissue calcification. Despite its
      high prevalence, there are currently no clinically approved pharmaceuticals for
      the management of AVS. The objective of the current study was to elucidate the
      effects of an angiotensin II type 1 receptor blocker, alone or in combination
      with statin therapy, on the progression of AVS. METHODS: Male New Zealand white
      rabbits were fed an atherogenic diet for a period of 12 months to induce AVS.
      Once disease was established, rabbits were randomly assigned to receive no
      treatment, olmesartan medoxomil, atorvastatin calcium, or a combination of both
      drugs for a period of 6 months. Disease progression was monitored in vivo using
      clinically relevant magnetic resonance imaging, and aortic valve cusps were
      examined ex vivo using histologic and immunohistochemical methods. RESULTS: Cusp
      thickness significantly increased (0.58 +/- 0.03 vs 0.39 +/- 0.03 mm for
      cholesterol and control animals, respectively; P < 0.0001) and all classic
      hallmarks of disease progression-including lipid infiltration, inflammation, and
      tissue calcification-were observed after 12 months. Unfortunately, neither
      olmesartan medoxomil nor atorvastatin calcium were able to reverse or delay
      disease progression during the 6-month treatment period. However, several
      histologic changes were observed in the valvular microenvironment. CONCLUSIONS:
      The current study suggests that angiotensin receptor blockers, alone or in
      combination with statin therapy, may not be suitable for management of clinical
      AVS.

PMID- 24726091
TI  - Nonatherosclerotic coronary artery disease in young women.
AB  - BACKGROUND: Nonatherosclerotic coronary artery disease (NACAD) is an important
      cause of myocardial infarction (MI) in young women but is often missed on
      coronary angiography, especially spontaneous coronary artery dissection (SCAD).
      The prevalence of NACAD in young women has not been described. METHODS: We
      retrospectively reviewed all coronary angiograms of women aged 50 years and
      younger at Vancouver General Hospital from December 1, 2009 to November 30, 2011.
      The angiograms were reviewed by 2 experienced interventional cardiologists, and
      reported as normal (<30% stenosis), atherosclerotic coronary artery disease
      (ACAD), or NACAD. NACAD was further characterized as SCAD, coronary fibromuscular
      dysplasia (FMD), ectasia, vasculitis, embolism, congenital anomaly, or unclear
      etiology. RESULTS: Of 7605 coronary angiograms performed, 177 were done in women
      aged 50 years and younger. The mean age was 45.4 +/- 4.9 (range, 31-50) years, 76
      of 177 (42.9%) presented with acute coronary syndrome, and 66 were troponin
      positive. Ninety-seven (54.8%) women had normal arteries, 54 (30.5%) had ACAD, 23
      (13.0%) had NACAD, and 3 (1.7%) had unclear etiology. Of those with NACAD, SCAD
      was observed in 16 (all troponin-positive and 13 of 16 had noncoronary FMD), and
      2 had irregular beading suspicious of coronary FMD. Coronary vasculitis was
      suspected in 2, and 5 had coronary ectasia. Among women with MI (66/177), 19
      (28.8%) had normal arteries (3 Takotsubo cardiomyopathy), 24 (36.4%) had ACAD, 20
      (30.3%) had NACAD, 16 (24.2%) had SCAD, and 3 had unclear etiology. CONCLUSIONS:
      NACAD was not rare among young women (aged 50 years and younger) undergoing
      coronary angiography and was an important cause of MI, accounting for 30%. SCAD
      was the most commonly encountered NACAD in young women, causing 24% of MIs.

PMID- 24726092
TI  - Autologous transplantation of bone marrow/blood-derived cells for chronic
      ischemic heart disease: a systematic review and meta-analysis.
AB  - BACKGROUND: Studies focused on cell therapy for chronic ischemic heart disease
      (CIHD) have been published with conflicting results. In this meta-analysis, we
      aimed to assess the effectiveness and safety of autologous bone marrow/blood
      derived cell transplantation in patients with CIHD. METHODS: Randomized
      controlled trials (RCTs) were identified in PubMed, OVID, EMBASE, and Cochrane
      Library reviews and reference lists of relevant articles. Weighted mean
      difference was calculated for changes in left ventricular ejection fraction
      (LVEF), left ventricular end-systolic volume (LVESV), and left ventricular end
      diastolic volume (LVEDV) using a random-effects model. RESULTS: Nineteen trials
      with a total of 886 patients were included. Compared with controls, patients who
      received transplantation of bone marrow/blood-derived cells had significantly
      improved LVEF (3.54%; 95% confidence interval [CI], 1.92%-5.17%; P < 0.001) and
      LVESV (-8.96 mL; 95% CI, -13.64 to -4.28 mL; P < 0.001). No significant
      improvement in LVEDV (-0.75 mL; 95% CI, -9.80-8.30 mL; P = 0.22) was detected.
      Subgroup analysis revealed that significant improvement in LVEDV was observed in
      patients with lower baseline LVEF. Moreover, there were trends in favor of a
      benefit for LV function and remodelling when intramyocardial cells were injected
      during coronary bypass surgery and the bone marrow mononuclear cell number was <=
      1 * 10(8). Furthermore, cell therapy was associated with a significant decrease
      in all-cause death (relative risk: 0.49; 95% CI, 0.29-0.84; P = 0.01).
      CONCLUSIONS: Current evidence showed that cell therapy moderately improved left
      ventricle function and significantly decreased all-cause death in patients with
      CIHD and supports further RCTs with larger sample size and longer follow-up.

PMID- 24726093
TI  - Clinical, neurophysiological and pathological findings of HNPP patients with
      17p12 deletion: a single-centre experience.
AB  - BACKGROUND: Classic clinical manifestations of HNPP are characterized by
      recurrent painless mononeuropathies, but a minority of patients present with an
      atypical clinical pattern, including CMT-like neuropathy, acute or chronic
      inflammatory demyelinating neuropathy-like polyneuropathy, and carpal tunnel
      syndrome. Electrophysiological examination plays a central role in the diagnosis
      of HNPP, disclosing a non-uniform conduction slowing, more pronounced at
      entrapment sites. PATIENTS AND METHODS: We report clinical, electrophysiological
      and pathological findings from 73 patients with HNPP, coming from 53 unrelated
      families, followed at our Institute of Neurology over a 20-year period. RESULTS:
      Typical presentation with recurrent multiple mononeuropathies was observed in
      28/64 (44%) patients. In the remaining 36/64 (56%), we observed an atypical
      clinical presentation, characterized by generalized weakness and cramps, chronic
      ulnar neuropathy, carpal tunnel syndrome, chronic sensory polyneuropathy,
      Guillain-Barre-like presentation, and CMT-like presentation. Nine patients were
      asymptomatic for neuropathic symptoms. Nerve conduction studies showed in all
      cases a sensori-motor demyelinating polyneuropathy with conduction abnormalities
      preferentially localized at common entrapment sites. When performed, sural nerve
      biopsy disclosed the focal thickening of the myelin sheath in all patients.
      CONCLUSIONS: About half of the patients with HNPP from our cohort showed an
      atypical clinical presentation. Neurophysiological examination represents the
      main tool for a proper diagnosis.

PMID- 24726094
TI  - Dosing of raltegravir when given with rifampicin.

PMID- 24726096
TI  - Arterial stiffness in patients with bronchial asthma.

PMID- 24726097
TI  - Tracking Lung Clearance Index and chest CT in mild cystic fibrosis lung disease
      over a period of three years.
AB  - INTRODUCTION: Lung disease remains the main cause of morbidity and mortality in
      patients with Cystic Fibrosis (CF). To detect lung disease before clinical
      symptoms become apparent, sensitive tools are essential. Spirometry is used for
      monitoring, but the FEV1 remains frequently normal throughout childhood. The Lung
      Clearance Index (LCI) calculated from Multiple Breath Washout (MBW) was
      introduced at the CF centre Innsbruck in 2007 for assessing ventilation
      inhomogeneity in patients with mild lung disease. We hypothesized that LCIs in
      2007 are of prognostic value for the presence or absence of structural lung
      changes in later years. METHODS: Between 2007 and 2010 MBW, spirometry and ultra
      low-dose HR-CT were prospectively tracked in 36 patients (6-53 years) with a mean
      FEV1 >= 80% predicted in 2007. RESULTS: At study start the majority of patients
      had abnormal CT scores and LCI results. While CT and spirometry remained largely
      stable throughout the study, LCI results slightly improved but still correlated
      with CT scores in 2010. LCI results in 2007 correlated with CT scores in 2010
      while FEV1 did not. In 86% the LCI value in 2007 was indicative for the presence
      or absence of structural lung changes in 2010. CONCLUSION: The LCI is a sensitive
      tool for detecting and tracking pulmonary changes. Extended structural changes
      are unlikely if the LCI is normal. The LCI has the potential to be used for
      monitoring the progression of early CF lung disease and assessing the effect of
      treatment in both clinical care and research settings.

PMID- 24726095
TI  - Raltegravir for the treatment of patients co-infected with HIV and tuberculosis
      (ANRS 12 180 Reflate TB): a multicentre, phase 2, non-comparative, open-label,
      randomised trial.
AB  - BACKGROUND: Concurrent treatment of HIV and tuberculosis is complicated by drug
      interactions. We explored the safety and efficacy of raltegravir as an
      alternative to efavirenz for patients co-infected with HIV and tuberculosis.
      METHODS: We did a multicentre, phase 2, non-comparative, open-label, randomised
      trial at eight sites in Brazil and France. Using a computer-generated
      randomisation sequence, we randomly allocated antiretroviral-naive adult patients
      with HIV-1 and tuberculosis (aged >=18 years with a plasma HIV RNA concentration
      of >1000 copies per mL) to receive raltegravir 400 mg twice a day, raltegravir
      800 mg twice daily, or efavirenz 600 mg once daily plus tenofovir and lamivudine
      (1:1:1; stratified by country). Patients began study treatment after the start of
      tuberculosis treatment. The primary endpoint was virological suppression at 24
      weeks (HIV RNA <50 copies per mL) in all patients who received at least one dose
      of study drug (modified intention-to-treat analysis). We recorded death, study
      drug discontinuation, and loss to follow-up as failures to achieve the primary
      endpoint. We assessed safety in all patients who received study drugs. This study
      is registered in ClinicalTrials.gov, number NCT00822315. FINDINGS: Between July
      3, 2009, and June 6, 2011, we enrolled and randomly assigned treatment to 155
      individuals; 153 (51 in each group) received at least one dose of the study drug
      and were included in the primary analysis. 133 patients (87%) completed follow-up
      at week 48. At week 24, virological suppression was achieved in 39 patients (76%,
      95% CI 65-88) in the raltegravir 400 mg group, 40 patients (78%, 67-90) in the
      raltegravir 800 mg group, and 32 patients (63%, 49-76) in the efavirenz group.
      The adverse-event profile was much the same across the three groups. Three (6%)
      patients allocated to efavirenz and three (6%) patients allocated to raltegravir
      800 mg twice daily discontinued the study drugs due to adverse events. Seven
      patients died during the study (one in the raltegravir 400 mg group, four in the
      raltegravir 800 mg group, and two in the efavirenz group): none of the deaths was
      deemed related to study treatment. INTERPRETATION: Raltegravir 400 mg twice daily
      might be an alternative to efavirenz for the treatment of patients co-infected
      with HIV and tuberculosis. FUNDING: French National Agency for Research on AIDS
      and Viral Hepatitis (ANRS), Brazilian National STD/AIDS Program-Ministry of
      Health.

PMID- 24726098
TI  - Blood pressure control and perceived health status in African Americans with
      subclinical hypertensive heart disease.
AB  - The role of antihypertensive therapy in reducing the risk of cardiovascular
      complications such as heart failure is well established, but the effects of
      different blood pressure goals on patient-perceived health status has not been
      well defined. We sought to determine if adverse effects on perceived health
      status will occur with lower blood pressure goals or more intensive
      antihypertensive therapy. Data were prospectively collected as a part of a single
      center, randomized controlled trial designed to evaluate standard (Seventh Joint
      National Committee on Prevention, Detection, Evaluation and Treatment of High
      Blood Pressure-compliant) versus intense (<120/80 mm Hg) blood pressure goals for
      patients with uncontrolled hypertension and subclinical hypertensive heart
      disease. Blood pressure management was open label, and health status was measured
      at 3-month intervals over 1 year of follow-up using the short-form (SF)-36. Mixed
      linear models were constructed for each of the SF-36 summary scores. One hundred
      twenty-three (mean age 49.4 +/- 8.2; 65% female; 95.1% African American) patients
      were randomized, 88 of whom completed the protocol. With the exception of a
      decrease in perceived health transition, health status did not change
      significantly on repeat measurement. Lower blood pressure goals and more
      intensive antihypertensive therapy appear to be well tolerated with limited
      effects on patients' perception of health status. 

PMID- 24726099
TI  - Telmisartan improves survival and ventricular function in SHR rats with extensive
      cardiovascular damage induced by dietary salt excess.
AB  - Excessive dietary salt intake induces extensive cardiovascular and renal damage
      in spontaneously hypertensive rats (SHR) that may be prevented by
      antihypertensive agents. This study examines whether salt-induced cardiac damage
      may be reversed by angiotensin II (type 1) receptor blockade (telmisartan). Eight
      week-old male SHRs were divided into four groups; Group 1 (NS) was fed regular
      rat chow, and Group 2 (HS) received high-salt diet (HS; 8% NaCl). After 8 weeks
      on their respective diets, systemic hemodynamics and indices of left ventricular
      (LV) function were determined. Group 3 (HSnoT) was given HS for 8 weeks and then
      switched to a regular chow (0.6% NaCl) diet with no other treatment, and Group 4
      (HSArb) received HS for 8 weeks and was then given regular diet plus telmisartan.
      Rats from these latter two groups were monitored for the ensuing 30 days.
      Compared with the NS group, rats in the HS group exhibited increased mean
      arterial pressure (161 +/- 7 vs. 184 +/- 8 mm Hg) and LV diastolic dysfunction,
      as evidenced by a decreased rate of LV pressure decline (-8754 +/- 747 vs. -4234
      +/- 754 mmHg/sec) at the end of the 8 weeks of their respective treatment. After
      switching to regular chow, only one of 11 rats in the HSnoT group survived for
      the 30 days, whereas 10 died within 18 days; in the HSArb group only one of nine
      rats died; eight survived 30 days (P < .01). Telmisartan significantly improved
      LV function and survival in those SHR rats having extensive cardiovascular damage
      induced by dietary salt excess.

PMID- 24726100
TI  - Insulin-like growth factor-1 (IGF-1) enhances developmental competence of cat
      embryos cultured singly by modulating the expression of its receptor (IGF-1R) and
      reducing developmental block.
AB  - OBJECTIVE: The aim of this study is to determine the effects of insulin-like
      growth factor-1 (IGF-1) and the mRNA expression of IGF-1 receptor (IGF-1R) during
      the in vitro development of cat embryos cultured in groups versus singly.
      METHODS: Cumulus-oocyte complexes (COCs) were matured and fertilized in vitro
      with frozen-thawed semen. Cleaved embryos (48h post-fertilization) were randomly
      assigned to one of the following treatments: 1) group embryo culture without IGF
      1 (10 embryos per 50MUl droplet), 2) single-embryo culture without IGF-1, and 3)
      to 6) single-embryo culture (50MUl droplet per embryo) supplemented with
      different concentrations of IGF-1 (5, 25, 50 and 100ng/ml, respectively). During
      in vitro culture, the embryos were analyzed for development to the morula,
      blastocyst and hatching blastocyst stage. Relative mRNA expression of IGF-1R was
      also examined by qPCR at the morula and blastocyst stages. In addition, the mRNA
      expression of IGF-1R in morula-stage embryos treated with IGF-1 was determined.
      The influence of IGF-1 to preimplantation embryo development was then explored by
      co-incubation with 0.5MUM IGF-1R inhibitor (Picropodophyllin; PPP). RESULTS:
      Group embryo culture led to a significantly higher blastocyst development rate
      compared with single-embryo culture (P<0.05). The poor development of singly
      cultured embryos coincided with the significantly lower IGF-1R expression in
      morulae than in group-cultured morulae. IGF-1 (25 or 50ng/ml) supplementation
      significantly improved the blastocyst formation rate of single embryos to a level
      similar to group culture by promoting the morula-to-blastocyst transition. IGF-1
      supplementation (25 or 50ng/ml) of singly cultured embryos upregulated the
      expression of IGF-1R mRNA in morula-stage embryos to the same level as that
      observed in group-cultured embryos (without IGF-1). The beneficial effects of IGF
      1 on singly cultured embryo were (P<0.05) suppressed by PPP even in the group
      culture embryo without growth factor supplementation. CONCLUSION: IGF-1
      supplementation improves the developmental competence of feline embryos cultured
      individually and also increases IGF-1R gene expression to levels similar to group
      cultured embryos.

PMID- 24726101
TI  - Congenital Morgagni's hernia: a national multicenter study.
AB  - BACKGROUND: Congenital Morgagni's hernia (CMH) is rare and represents less than
      5% of all congenital diaphragmatic hernias. This is a national review of our
      experience with CMH outlining clinical presentation, methods of diagnosis,
      associated anomalies, treatment, and outcome. PATIENTS AND METHODS: The medical
      records of all patients with the diagnosis of CMH treated at four pediatric
      surgery units in Saudi Arabia were retrospectively reviewed for age at diagnosis,
      sex, presenting symptoms, associated anomalies, diagnosis, operative findings,
      treatment, and outcome. RESULTS: During a 20-year period (January 1990-December
      2010), 53 infants and children with CMH were treated. There were 38 males and 15
      females. Their age at diagnosis ranged from 1 month to 9 years (mean 22.2
      months). Forty-three (81%) presented with recurrent chest infection. Twenty-two
      (44.5%) had right CMH, 15 (28.3%) had left-sided hernia and 16 (30.2%) had
      bilateral hernia. In 7, the diagnosis of bilaterality was made at the time of
      surgery. Associated anomalies were seen in 38 (71.7%). Twenty-one (39.6%) had
      congenital heart disease, 8 (15%) had malrotation, and 15 (28.3%) had Down
      syndrome. All were operated on. Twenty-nine (54.7%) underwent repair via an open
      approach. The remaining 24 (45.3%) underwent repair using minimal invasive
      surgery, laparoscopic-assisted hernia repair (19 patients) or totally
      laparoscopic approach (5 patients). At the time of surgery, the hernia sac
      content included the colon in 33 (62.3%), part of the left lobe of the liver in
      13 (24.5%), the small intestines in 11 (20.75%), the omentum in 5 (9.4%), and the
      stomach in 4 (7.5%). In 12 (22.6%), the hernia sac was empty. When compared to
      the open repair, the laparoscopic-assisted approach was associated with a shorter
      operative time, an earlier commencement of feeds, less requirement for
      postoperative analgesia, a shorter hospital stay, and better cosmetic appearance.
      There was no mortality. On follow-up, 2 (7%) of the open surgical group developed
      recurrence. CONCLUSIONS: CMH is rare and in the pediatric age group commonly
      presents with recurrent chest infection and has a high incidence of associated
      anomalies, commonly congenital heart disease and Down syndrome. We advocate a
      laparoscopic-assisted approach to repair CMH. This is a simple technique that
      produces a sound repair, and when compared with the open approach it takes less
      operative time, requires less analgesia, allows earlier commencement of feeds, is
      associated with a shorter hospital stay, and has a better cosmetic outcome.

PMID- 24726102
TI  - Prognostic value of abdominal sonography in necrotizing enterocolitis of
      premature infants born before 33 weeks gestational age.
AB  - OBJECTIVE: The purpose of this study was to assess the prognostic value of
      abdominal sonography in necrotizing enterocolitis (NEC) in preterm infants with a
      gestational age less than 33 weeks of gestation, using surgery and/or death as
      the primary outcome and stenosis as the secondary outcome. METHODS: A
      retrospective study of 95 premature infants (mean gestational age: 28.6 weeks),
      presenting with NEC between January 2009 and November 2011 and who underwent
      plain abdominal radiography and sonography, was performed. In uni- and
      multivariate analyses, radiographic and sonographic findings were correlated with
      complications ('surgery and/or death' and 'stenosis'). RESULTS: Sonographic
      findings of free intraperitoneal air (odd ratio [OR]=8.0; IC, 1.4-44.2), free
      abdominal fluid (OR 3.5; IC 1.3-9.4), portal venous gas (OR 3.9; IC, 1.2-12.9),
      and bowel wall thickening (OR 2.8; IC,1.1-7.2) were significantly associated with
      surgery and/or death. Intramural gas was significantly correlated (OR=11.8; IC,
      1.5-95.8) with intestinal stenosis following NEC. None of the radiographic
      findings were associated with complications. CONCLUSION: Abdominal sonography is
      a reliable tool for the prognostic assessment of NEC in preterm infants.

PMID- 24726103
TI  - Anomalies associated with gastroschisis and omphalocele: analysis of 2825 cases
      from the Texas Birth Defects Registry.
AB  - BACKGROUND/PURPOSE: The increasing prevalence of abdominal wall defects prompted
      analysis of anomalies associated with gastroschisis and omphalocele in the Texas
      Birth Defects Registry (TDBR). METHODS: Cases of gastroschisis (ICD9 code
      756.71), omphalocele (756.70), and/or unspecified anomalies of the abdominal wall
      (756.79) were obtained from the TDBR after IRB approval and analyzed using
      Microsoft Access(c) and Excel(c) databases. RESULTS: Analysis began with 2825
      cases including 1831 of gastroschisis, 814 of omphalocele, and 180 of unspecified
      abdominal wall defects plus 9680 associated anomalies that were classified
      according to system. The overall prevalence of abdominal wall defects among
      3,806,299 Texas births from 1999 to 2008 was 7.4 per 10,000 with 4.8 per 10,000
      for gastroschisis and 2.1 for omphalocele. After excluding ambiguous cases (8.5%
      possibly misclassified), anomaly spectra were similar for the two AWD with
      musculoskeletal (limb contractures or defects), cardiovascular, gastrointestinal,
      urogenital, and central nervous system defects being most common. Of 1831 cases
      with gastroschisis, 594 (32%) had associated anomalies compared to 654 (80%) of
      814 omphalocele cases. CONCLUSIONS: Gastroschisis as well as omphalocele has
      significant associated anomalies that are important to appreciate during pre- and
      postnatal management.

PMID- 24726104
TI  - Rotavirus particles in the extrahepatic bile duct in experimental biliary
      atresia.
AB  - BACKGROUND: Biliary atresia (BA) is the most common indication for liver
      transplantation in children. The experimental model of BA, induced by rotavirus
      infection in neonatal mice, has been widely used to investigate the inflammatory
      aspects of this disease. We investigated the kinetics and the localization of the
      viral infection in this murine model. METHODS: In this study 399 animals were
      employed for a detailed investigation of rhesus rotavirus (RRV)-induced BA. RRV
      kinetics was analyzed by rtPCR and its (sub) cellular localization investigated
      using whole mounts which were further processed for confocal and electron
      microscopy. RESULTS: The BA mouse model resulted in up to 100% induction of
      atresia following RRV injection. The kinetics of RRV infection differed between
      liver and extrahepatic bile ducts. While the virus peak up to day 10
      postinfection was similar in both organs, the virus remained detectable in
      extrahepatic bile duct cells up to day 21. Interestingly, RRV particles were
      localized not only in cholangiocytes but also in cells of the subepithelial
      layers, potentially macrophages. CONCLUSIONS: RRV remains present in the
      extrahepatic bile duct cells after an initial virus peak. Viral particles were
      detected in subepithelial cells in contrast to the described tropism toward
      cholangiocytes.

PMID- 24726105
TI  - Living donor liver transplantation in children: should the adult donor be
      operated on by an adult or pediatric surgeon? Experience of a single pediatric
      center.
AB  - BACKGROUND/PURPOSE: Living donor liver transplantation has become a cornerstone
      for the treatment of children with end-stage hepatic dysfunction, especially
      within populations or countries with low rates of organ utilization from deceased
      donors. The objective is to report our experience with 185 living donors operated
      on by a team pediatric surgeons in a tertiary center for pediatric liver
      transplantation. METHODS: Retrospective analysis of medical records of donors of
      hepatic grafts for transplant undergoing surgery between June 1998 and March
      2013. RESULTS: Over the last 14 years, 185 liver transplants were performed in
      pediatric recipients of grafts from living donors. Among the donors, 166 left
      lateral segments (89.7%), 18 left lobes without the caudate lobe (9.7%) and 1
      right lobe (0.5%) were harvested. The donor age ranged from 16 to 53 years, and
      the weight ranged from 47 to 106 kg. In 10 donors, an additional graft of the
      donor inferior mesenteric vein was harvested to substitute for a hypoplastic
      recipient portal vein. The transfusion of blood products was required in 15
      donors (8.1%). The mean hospital stay was 5 days. No deaths occurred, but
      complications were identified in 23 patients (12.4%): 9 patients experienced
      abdominal pain and severe gastrointestinal symptoms and 3 patients required
      reoperations. Eight donors presented with minor bile leaks that were treated
      conservatively, and 3 patients developed extra-peritoneal infections (1 wound
      collection, 1 phlebitis and 1 pneumonia). Eight grafts (4.3%) showed primary
      dysfunction resulting in recipient death (3 cases of fulminant hepatitis, 1
      patient with metabolic disease, 1 patient with Alagille syndrome and 3 cases of
      biliary atresia in infants under 1 year old). There was no relation between donor
      complications and primary graft dysfunction (P=0.6). CONCLUSIONS: Living donor
      transplantation is safe for the donor and presents a low morbidity. The donor
      surgery may be performed by a team of trained pediatric surgeons.

PMID- 24726106
TI  - Role of surgery in the treatment of patients with high-risk neuroblastoma who
      have a poor response to induction chemotherapy.
AB  - BACKGROUND: In instances of high-risk neuroblastoma that do not show a clinical
      response to induction therapy, whether it is worth performing surgical resection
      or not and whether gross total resection (GTR) is more important than subtotal
      resection (STR) remain controversial. METHODS: We retrospectively analyzed the
      data of patients with stage 4 neuroblastoma aged 18 months or older at diagnosis.
      Primary tumor volumes were measured both at diagnosis and at the first tumor
      response evaluation (after 6 cycles of induction chemotherapy). If the tumor
      volume at the first response evaluation was > 50% of the initial tumor volume,
      the patient was categorized as a poor responder. Otherwise, the patient was
      categorized as a good responder. Only poor responders were included. Patients
      were evaluated for event-free survival (EFS), overall survival (OS), and
      complications of surgery based on extent of surgical intervention. RESULTS: Sixty
      five patients were included in this study. The 41 patients who underwent surgical
      intervention had a higher 3-year OS than the 24 patients who had a biopsy only
      (55.4% +/- 8.1% vs. 31.3% +/- 10.2%, P=0.02). However, there was limited
      improvement in 3-year EFS following surgical intervention. Three-year EFS rates
      of BX group (biopsy only) and OP group (surgical resection) were 24.2% +/- 9.3%
      and 37.7% +/- 7.9%, respectively (P=0.063). The extent of resection had no impact
      on 3-year OS (P=0.631) and 3-year EFS (P=0.796). Patients in the GTR group
      trended to have more severe surgical complications than patients in the STR group
      (P=0.105). CONCLUSIONS: For high-risk neuroblastomas that do not show a clinical
      response to induction therapy, surgical resection is important in predicting
      outcome, but the extent of resection is not.

PMID- 24726107
TI  - Pancreaticoduodenectomy for malignancies in children.
AB  - PURPOSE: Malignant tumors of the common bile duct or of the pancreas head are
      uncommon in childhood [Perez EA, Gutierrez JC, Koniaris LG, Neville HL, Thompson
      WR, Sola JE. Malignant pancreatic tumors: incidence and outcome in 58 pediatric
      patients. J Pediatr Surg. 2009; Jan; 44 (1): 197-203]. With radical surgery being
      the standard cure for nonmetastatic diseases, pancreaticoduodenectomy (PD) is the
      best choice when the tumor is localized in the head of the pancreas, or in the
      lower portion of the common bile duct. The purpose of the present study is to
      describe five consecutive children managed by PD, and reviewing the particular
      aspects and results of this rare procedure in children. METHODS: Between 2007 and
      2010, five patients (median age: 7 years) underwent PD for nonmetastatic
      malignant tumors. In two cases, PD was performed en bloc with a right hepatectomy
      in order to achieve the radical resection of a recurrent biliary sarcoma. Four
      patients benefited from a "pylorus-preserving" PD procedure. In two patients,
      resection of the portal vein and vascular reconstruction was performed, and in
      one case, an extended resection of the biliary ductal system was necessary.
      RESULTS: All resection margins were clear. The postoperative course was
      uneventful, with no pancreatic or biliary leakage in all of the patients. Oral
      refeeding was achieved by the eighth postoperative day. In two cases, a late
      revision of pancreatic-jejunal anastomosis was performed because of mild
      steatorrea and a suspected anastomotic stricture. Two of the patients, who were
      subsequently operated on second hand, for biliary sarcoma, died from the
      recurrence; while three of the others, with pancreatic malignancies, are alive
      and well, with a good functional outcome. CONCLUSIONS: Surgical resection is the
      treatment of choice for tumors of the pancreatic head area. In the absence of
      regional or metastatic extension, the radicality of primary intervention is
      associated with favorable outcomes. Good functionality results were observed
      after the PD was limited to the head of the pancreas and subject to pylorus
      preserving techniques.

PMID- 24726108
TI  - Biological characteristics of pediatric renal cell carcinoma associated with
      Xp11.2 translocations/TFE3 gene fusions.
AB  - PURPOSE: To investigate the clinical features of pediatric Xp11.2 translocation
      renal cell carcinoma (RCC). METHODS: A retrospective review of 22 cases over 35
      years. RESULTS: Xp11.2 translocation RCCs were identified in 13 boys and 9 girls
      with a median age of 10.5 years (range: 2.5-16 years). RCC presented with
      hematuria in 17, abdominal mass in 1, abdominal masses with hematuria in 2,
      abdominal pain with hematuria in 1, and as an incidental finding in 1 patient.
      Ten patients were classified stage I, 10 were stage III, and two were stage IV.
      Of the 10 patients with stage I RCCs, 3 patients with tumor measuring less than 7
      cm had nephron-sparing surgery (NSS) and 17 patients underwent simple
      nephrectomy. A 15-cm tumor was incompletely removed in one patient and another
      patient with a 25-cm * 18-cm * 15-cm tumor had gross residual. Of the 15 patients
      followed up between 6 months and 35 years, 13 were still living and 2 had died
      after surgery. CONCLUSIONS: Xp11.2 translocation RCC is the predominant form of
      pediatric RCC, associated with advanced stage at presentation. Nephrectomy is the
      usual treatment for RCC but NSS is an option for patients with tumors measuring<7
      cm. Patients with N+M0 maintained a favorable prognosis following surgery alone.

PMID- 24726109
TI  - Metachronous benign ovarian tumors are not uncommon in children.
AB  - PURPOSE: To evaluate the risk for metachronous ovarian tumor in pediatric
      patients with mature ovarian teratoma. METHODS: During 1981-2011, 22 children
      underwent oophorectomy for mature teratoma at the median age of 11.4 (range 1.5
      15.3) years. The patients were followed-up in median 4.4 (range 0.5-25.5) years.
      RESULTS: None of the patients had synchronous bilateral tumor at the time of
      primary operation, but during follow-up five patients (23%) got metachronous
      contralateral ovarian tumor. The contralateral tumor was observed in median 3.6
      (range 1-8.8) years after the primary operation. According to Kaplan-Meier
      analysis the risk for contralateral tumor was 14% +/- 8% (SE) within five years
      and 66% +/- 26% (SE) within 10 years. In this series, the contralateral tumor was
      operated by ovary preserving surgery. Three of the metachronous tumors were
      mature teratomas and two were seromucinous infantile cystadenomas. One patient
      had a second teratoma recurrence 14 years after the first recurrence.
      CONCLUSIONS: More than one fifth of the children with ovarian mature teratoma get
      metachronous benign tumor to the contralateral ovary. Therefore a yearly
      ultrasound follow-up is needed for these patients up to potential pregnancy to
      enable early diagnosis, ovary preserving surgery and maintenance of fertility in
      the case of metachronous tumor.

PMID- 24726110
TI  - Preoperative multiple endocrine neoplasia type 1 diagnosis improves the surgical
      outcomes of pediatric patients with primary hyperparathyroidism.
AB  - BACKGROUND: Primary hyperparathyroidism (PHPT) is uncommon in children. The
      surgical management of PHPT in children has evolved over the past two decades.
      METHODS: A retrospective study of patients who underwent parathyroidectomy for
      PHPT diagnosed at age < 18 years and managed at a tertiary referral center for
      endocrine and familial disorders. RESULTS: Thirty-eight patients met eligibility
      criteria (1981-2012). Median age at PHPT diagnosis was 15 years. Two-thirds of
      patients were symptomatic (68%, n=26), most commonly from nephrolithiasis. Twenty
      six (68%) patients underwent a standard cervical exploration while 32% underwent
      a focused unilateral parathyroidectomy. Multiple endocrine neoplasia type 1
      (MEN1) was diagnosed preoperatively in 22/26 patients. Patients with a
      preoperative diagnosis of MEN1 were more likely to undergo a complete initial
      operation (>= 3 gland parathyroidectomy with transcervical thymectomy, 13/22, 59%
      vs. 0/4, 0%; P=0.03) and less likely to have recurrent disease (10/22, 45% vs.
      3/4, 75%; P<0.001) during follow up than patients diagnosed postoperatively.
      CONCLUSIONS: Children with PHPT should raise suspicion for MEN1. Preoperative
      MEN1 evaluation helped guide the extent of initial parathyroidectomy and was
      associated with lower rates of recurrence in sporadic and familial PHPT in
      pediatric patients. Management should occur at a high volume center with
      experienced clinicians and genetic counseling services.

PMID- 24726111
TI  - Perioperative epidural analgesia in children undergoing major abdominal tumor
      surgery--a single center experience.
AB  - PURPOSE: The purpose of this study was to assess the use of continuous epidural
      analgesia in pediatric patients undergoing major abdominal tumor surgery.
      METHODS: Children undergoing major abdominal tumor surgery at our institution
      between 2008 and 2012 (n=40) received continuous epidural analgesia via an
      epidural catheter. Surgical trauma scores, pain scores, and clinical data of the
      children were compared to a pair-matched historical control group operated on
      between 2002 and 2007 without epidural analgesia. RESULTS: Pain levels in the
      study group on day 1 and 3 after surgery were lower compared to the control
      group. The differences did, however, not reach statistical significance (p=0.15
      and 0.09). Children in the study group received significantly fewer additional
      doses of piritramide or morphine (45% versus 82%, p<0.001). Despite significantly
      higher surgical trauma scores in the study group (p=0.018), there were no
      statistical differences regarding clinical parameters, such as mechanical
      ventilation time, time on intensive care unit, and total hospital stay. There
      were no catheter-related complications. CONCLUSIONS: Continuous epidural
      analgesia is beneficial for children undergoing complex abdominal tumor surgery
      with regard to pain levels, postoperative recovery, and general clinical course.
      Expertise of the managing team, a careful patient selection, and a continuous
      quality assessment are essential for success.

PMID- 24726112
TI  - Early versus late reconstruction of cloacal malformations: the effects on
      postoperative complications and long-term colorectal outcome.
AB  - INTRODUCTION: Patients with a cloacal malformation generally undergo
      reconstructive surgery within the first years of life. However, the ideal age for
      surgery has rarely been mentioned. The aim of this study was to report
      differences in outcome between early (<6 months) and late repair of cloacal
      malformations. METHODS: Charts of patients with a cloacal malformation treated in
      5 pediatric surgical centers between 1985 and 2009 were retrospectively studied
      for associated anomalies, postoperative complications, and colorectal and
      urological outcome. RESULTS: Forty-two patients were eligible for this study,
      giving a mean exposure of less than 1 patient yearly per center. Forty-five
      percent of the patients had a short common channel (>3 cm), and 14% had a long
      common channel. Length of common channel was missing in 41% of the patients.
      Median age of the cloacal reconstruction was 9 months (range 1-121 months).
      Twelve patients (29%) underwent an early surgical repair (within the first 6
      months of age; median 3 months), and 30 (71%) patients underwent a late repair
      (after 6 months of age; median 14 months). Eighteen postoperative complications
      (<30 days) had been documented in 15 patients (35%), with significant more
      perineal wound dehiscences in patients with an early repair (42% vs. 10%,
      p=0.031). There were no differences in complication rate between patients with
      short and long common channels. Mean follow-up was 142 months (range 15-289). At
      the last follow-up, 10 patients (24%) had voluntary bowel movements. Fourteen
      patients (33%) had complaints of soiling, 25 (60%) were constipated, with no
      differences between the early and late repair groups. Patients in the late repair
      group as well as the group of patients with a short common channel were more
      frequently able to void spontaneously. CONCLUSIONS: Postoperative complications
      are common in patients with cloacal malformations. Early repair is associated
      with more wound dehiscences, however, without affecting long-term functional
      outcome. All centers had limited annual exposure of less than 1 patient. In these
      clinical settings, ideal age of cloacal reconstruction seems to be between 6 and
      12 months. In general, centralized care for these complex malformations may be
      the crucial factor for reducing postoperative complications and better long-term
      outcome.

PMID- 24726113
TI  - Long term outcomes of laparoscopic-assisted anorectoplasty: a comparison study
      with posterior sagittal anorectoplasty.
AB  - PURPOSE: The aim of this study is to compare the long term outcomes between
      laparoscopic-assisted anorectoplasty (LAARP) and posterior sagittal
      anorectoplasty (PSARP) for children with rectobladderneck and rectoprostatic
      fistula anorectal malformations (ARM). METHODS: Thirty-two ARM children with
      rectobladderneck and rectoprostatic fistula who underwent LAARP between October
      2001 and March 2012 were reviewed. The outcomes were compared with those of 34
      ARM children who underwent PSARP between August 1992 and September 2001. The
      sacral ratio (SR), age at operation, operative time, postoperative hospital stay
      and complications were evaluated. Bowel functions were assessed using the
      Krickenbeck classification. RESULTS: The mean operative time of the LAARP was
      significantly shorter than that of PSARP group (1.62 +/- 0.40 vs 2.13 +/- 0.30
      h). The postoperative hospital stay was significantly shorter in the LAARP group
      (5.8 +/- 0.65 vs 8.4 +/- 0.67 h). The wound infections (11.8% vs 0%) and
      recurrent fistula (11.8% vs 0%) were more common in PSARP patients. Th e overall
      morbidity rate of PSARP group was significantly higher than that of the LAARP
      group (35.3% vs 12.5%, p<0.05). However, 7.5% of the LAARP patients developed
      rectal prolapse. Twenty-four of 32 patients were followed up for more than 3
      years in LAARP group. The median follow up period was 7.5 years (range 4-11) in
      LAARP patients and 15.5 years (range 11-20) in PSARP patients. The rates of
      voluntary bowel movement, soiling (grade 1, 2 & 3) were similar in both groups.
      More patients from PSARP group developed grade 2 or 3 constipation (22.5% vs 0%,
      P<0.01). CONCLUSIONS: Compared to PSARP, LAARP is a less invasive procedure. The
      long term functional outcomes after LAARP were equivalent if not better than
      those of PSARP.

PMID- 24726114
TI  - Megarectosigmoid in children with anorectal malformations: long term outcome
      after surgical or conservative treatment.
AB  - PURPOSE: Megarectosigmoid (MRS) is commonly seen in children with anorectal
      malformations (ARM) and contributes to the high incidence of constipation.
      Surgical resection has been advocated by some, whereas others propose intense
      bowel management as the treatment of choice. The aim of this study was to
      evaluate outcome of both bowel function and configuration after surgical or
      conservative treatment of MRS in ARM patients. MATERIALS AND METHODS: The study
      included 79 patients with ARM, excluding perineal fistula, (48 boys, 31 girls)
      from 1986 to 2007. MRS was diagnosed at colostomy formation or contrast enema
      performed in the neonatal period. Early in the period, the majority of the
      patients were treated surgically, whereas in the late 1990 s, a conservative
      approach with intensified bowel treatment was implemented. Contrast enema and
      bowel function investigations were performed repeatedly during follow-up.
      RESULTS: MRS, according to radiological criteria, was diagnosed in 26/79 (33%) of
      the ARM children. Bowel functional outcome was similar regardless of surgical or
      conservative treatment and comparable to function in ARM children with non-MRS.
      The radiological signs of rectal dilatation and elongation disappeared after
      surgical intervention, but normalisation of the rectosigmoidal configuration was
      also seen with age in the conservative group. CONCLUSIONS: Bowel functional
      outcome in ARM children with MRS was similar after either surgical or
      conservative treatment during follow-up. The radiological signs of rectal
      dilatation and elongation disappeared also in the conservatively treated patients
      over time.

PMID- 24726115
TI  - Restorative proctocolectomy with J-pouch ileoanal anastomosis for total colonic
      aganglionosis among neonates and infants.
AB  - BACKGROUND: No consensus exists on the optimal surgical management of total
      colonic aganglionosis (TCA). Outcomes after restorative proctocolectomy (RPC) as
      the initial reconstructive procedure among neonatal and infant TCA patients have
      not been evaluated previously. METHODS: Medical records of patients with
      Hirschsprung disease (HD) who underwent RPC during infancy between 1997 and 2012
      (n=8) were reviewed. Bowel function and satisfaction with operative results were
      assessed in a follow-up interview. RESULTS: Median age at RPC was 1.1 months, and
      covering loop ileostomies were closed 3.7 months later. No operative
      complications occurred. Hospitalizations for enterocolitis and obstruction
      occurred each in 50% of patients postoperatively. Enterocolitis-associated outlet
      obstruction occurred in one third of patients, most of whom responded well to
      intersphincteric botulinum toxin (botox) injections. No pouchitis or elevated
      fecal calprotectin levels (median 51 MUg/g) were observed. At last follow-up 3.2
      years after ileostomy closure, the median 24-hour stooling frequency was 3.5.
      None had socially limiting fecal incontinence or problems in holding back
      defecation. Parent satisfaction with operative results was high. CONCLUSIONS: The
      rate of postoperative enterocolitis was similar to other procedures, but a better
      functional outcome was achieved. Botox injections were effective for
      postoperative functional outlet obstruction. Short-term results following RPC
      among neonates and infants are promising.

PMID- 24726116
TI  - Perioperative strategies and technical modifications to the Nuss repair for
      pectus excavatum in pediatric patients: a large volume, single institution
      experience.
AB  - BACKGROUND: The safety and efficacy of minimally invasive pectus excavatum repair
      have been demonstrated over the last twenty years. However, technical details and
      perioperative management strategies continue to be debated. The aim of the
      present study is to review a large single-institution experience with the
      modified Nuss procedure. METHODS: A retrospective review was performed of
      patients who underwent primary pectus excavatum repair at a single tertiary
      hospital via a modified Nuss procedure that included: no thoracoscopy,
      retrosternal dissection achieved via a left-to-right thoracic approach, four
      point stabilization of the bar, and no routine epidural analgesia. Data collected
      included demographics, preoperative symptoms, operative characteristics, hospital
      charges and postoperative outcomes. RESULTS: A total of 336 pediatric patients
      were identified. No cardiac perforations occurred and the rate of pericarditis
      was 0.6%. Contemporary rates of bar displacement have fallen to 1.2%. Routine use
      of chlorhexidine scrub reduced superficial site infections to 0.7%. Two patients
      (0.6%) with severe recurrence required reoperation. Bars were removed after an
      average period of 31.7(SD 13.2) months, with satisfactory cosmetic and functional
      results in 94.9% of cases. CONCLUSIONS: We report here a single-institution large
      volume experience, including modifications to the Nuss procedure that make the
      technique simpler and safer, improve results, and minimize hospital charges.

PMID- 24726118
TI  - Pediatric surgery on YouTubeTM: is the truth out there?
AB  - BACKGROUND/PURPOSE: In 2000, we described the variability of pediatric surgical
      information on the Internet. Since then, online videos have become an
      increasingly popular medium for education and personal expression. The purpose of
      this study was to examine the content and quality of videos related to pediatric
      surgical diagnoses on the Internet. METHODS: YouTubeTM was searched for videos on
      gastroschisis, congenital diaphragmatic hernia, pediatric inguinal hernia, and
      pectus excavatum. The first 40 English language videos for each diagnosis were
      reviewed for owner and audience characteristics, content and quality. RESULTS: A
      small majority of videos were made by medical professionals (50.63%, vs. 41.25%
      by lay persons and 8.13% by fundraising organizations). Eighty percent of videos
      were intended for a lay audience. Videos by medical professionals were more
      accurate and complete than those posted by lay persons. CONCLUSIONS: The
      YouTubeTM videos varied significantly in content and quality. Videos by lay
      persons often focused on the emotional aspect of the diagnosis and clinical
      course. Videos by members of the medical profession tended to be more complete
      and accurate. These findings underscore the continued need for high quality
      pediatric surgical information on the Internet for patients and their families.

PMID- 24726117
TI  - Trans-scrotal varicocelectomy in adolescents: clinical and surgical outcomes.
AB  - BACKGROUND: The gold standard to treat varicocele in adolescents is still under
      discussion. The aim of this study is to evaluate the role of trans-scrotal
      varicocelectomy and show the results obtained by using local anesthesia in
      combination with preoperative sedation. MATERIALS AND METHODS: Between January
      2010 and January 2012, this surgical and anesthesiology procedure was proposed to
      study patients. Inclusion and exclusion criteria were created. Patients received
      trans-scrotal varicocelectomy with lymphatic and artery sparing technique under
      local anesthesia with mild sedation anesthesia. Patients were followed for 6
      months after surgery, and complications were recorded. RESULTS: Eighteen patients
      were treated with this technique. Three patients required additional sedation
      with propofol. None had recurrence of varicocele, and one patient showed post
      operative hydrocele. All patients were discharged within 24h following surgery.
      Three patients used ibuprofen and paracetamol for two days after surgery.
      CONCLUSIONS: Local anesthesia in the pediatric age group could be used for
      varicocelectomy with mild sedation anesthesia.

PMID- 24726119
TI  - Early tracheostomy improves outcomes in severely injured children and
      adolescents.
AB  - BACKGROUND: Early tracheostomy has been advocated for adult trauma patients to
      improve outcomes and resource utilization. We hypothesized that timing of
      tracheostomy for severely injured children would similarly impact outcomes.
      METHODS: Injured children undergoing tracheostomy over a 10-year period (2002
      2012) were reviewed. Early tracheostomy was defined as post-injury day <= 7. Data
      were compared using Student's t test, Pearson chi-squared test and Fisher exact
      test. Statistical significance was set at p<0.05 with 95% confidence intervals.
      RESULTS: During the 10-year study period, 91 patients underwent tracheostomy
      following injury. Twenty-nine (32%) patients were < 12 years old; of these, 38%
      received early tracheostomy. Sixty-two (68%) patients were age 13 to 18; of
      these, 52% underwent early tracheostomy. Patients undergoing early tracheostomy
      had fewer ventilator days (p=0.003), ICU days (p=0.003), hospital days (p=0.046),
      and tracheal complications (p=0.03) compared to late tracheostomy. There was no
      difference in pneumonia (p=0.48) between early and late tracheostomy. CONCLUSION:
      Children undergoing early tracheostomy had improved outcomes compared to those
      who underwent late tracheostomy. Early tracheostomy should be considered for the
      severely injured child. SUMMARY: Early tracheostomy is advocated for adult trauma
      patients to improve patient comfort and resource utilization. In a review of 91
      pediatric trauma patients undergoing tracheostomy, those undergoing tracheostomy
      on post-injury day <= 7 had fewer ventilator days, ICU days, hospital days, and
      tracheal complications compared to those undergoing tracheostomy after post
      injury day 7.

PMID- 24726120
TI  - Ghrelin is a suppressor of testicular damage following experimentally induced
      cryptorchidism in the rat.
AB  - BACKGROUND: Cryptorchidism is associated with increased level of reactive oxygen
      species and lipid peroxidation. This study was undertaken to examine the possible
      ghrelin ability in attenuation of testicular damage in response to elevated
      temperature. METHODS: Thirty male rats were subdivided into sham-operated,
      cryptorchidism-saline and cryptorchidism-ghrelin group. Bilateral cryptorchidism
      was induced in groups 2 and 3, surgically. The animals in group 3 were given
      ghrelin for 7 days and all testes were taken for biochemical and photomicrograph
      analysis. RESULTS: Glutathione peroxidase activity and glutathione content
      significantly promoted on day 7 in the cryptorchid rats treated by ghrelin.
      Catalase activity was higher in the ghrelin-exposed animals than the
      cryptorchidism-saline group on both experimental days. Although superoxide
      dismutase activity was elevated by ghrelin treatment on both days, it did not
      differ significantly. By contrast, significant reduction was observed in
      thiobarbituric acid reactive substances concentrations following ghrelin
      administration on day 7. Moreover, ghrelin could improve histopathological scores
      of the testes, and diminished formation of giant cells and tubular vacuolization.
      CONCLUSIONS: These findings indicate for the first time the novel evidence of
      ghrelin antioxidant properties in attenuation of rat testicular injury following
      experimentally induced cryptorchidism.

PMID- 24726121
TI  - Fertility potential in a cohort of 65 men with previously acquired undescended
      testes.
AB  - PURPOSE: To evaluate testicular function in men with previously acquired
      undescended testes (AUDT) in whom spontaneous descent was awaited until puberty
      followed by orchiopexy in case of nondescent. METHODS: Andrological evaluation
      including paternity, scrotal ultrasound, reproductive hormones, and semen
      analysis was performed in three groups: men with AUDT, healthy controls, and men
      with previously congenital undescended testes (CUDT). RESULTS: In comparison with
      controls, men with AUDT more often had significantly abnormal testicular
      consistency, smaller testes, lower sperm concentration, and less motile sperm.
      Except for more often a normal testicular consistency in men with AUDT, no
      differences were found between men with AUDT and men with CUDT. Also, no
      differences were found between men with AUDT which had spontaneously descended
      and men who underwent orchiopexy. CONCLUSIONS: Fertility potential in men with
      AUDT is compromised in comparison with healthy controls, but comparable with men
      with CUDT. This suggests that congenital and acquired UDT share the same
      etiology. No significant difference was found between men who had spontaneous
      descent and men needing orchiopexy. However, fertility potential is unknown for
      men after immediate surgery at diagnosis, and this should be a subject for future
      studies.

PMID- 24726122
TI  - Silver nanoparticle-coated suture effectively reduces inflammation and improves
      mechanical strength at intestinal anastomosis in mice.
AB  - BACKGROUND: Our previous studies have revealed that silver nanoparticles (AgNPs)
      had anti-inflammatory properties. In this study, we coated AgNPs onto the surface
      of absorbable suture, to further explore their anti-inflammatory efficacy and
      potential clinical application using an intestinal anastomosis model. METHODS:
      Layer-by-layer deposition was used to coat AgNPs on absorbable sutures. Scanning
      electron microscopy (SEM) was conducted to observe the morphology and
      distribution of AgNPs on suture surface. 1cm of either non-coated suture, suture
      coated with antibiotics or AgNPs-coated suture was placed on E. coli overlay of
      LB agar plates to test for bacterial inhibition. The respective sutures were then
      used for ileal anastomosis in mice. The anastomotic sites were harvested to
      investigate the degree of tissue inflammation and cell proliferation, as well as
      collagen deposition. Furthermore, burst pressure measurement was employed to test
      for mechanical properties. RESULTS: SEM observation indicated AgNPs could be
      immobilized and distributed on suture surface evenly. AgNPs-coated suture had the
      best in vitro anti-bacterial efficacy when compared with other groups. Subsequent
      immunohistochemistry in the intestinal anastomosis model showed significantly
      less inflammatory cell infiltration (macrophage and neutrophil) and better
      collagen deposition in the anastomotic tissue in the AgNPs-coated suture group.
      Burst pressure measurement in healed anastomosis further confirmed that AgNPs
      coated suture had better mechanical properties. CONCLUSION: Our study suggests
      that AgNPs-coated sutures can improve anastomosis healing due to better
      mechanical properties from reduced inflammation.

PMID- 24726123
TI  - Intra-abdominal venous thrombosis after colectomy in pediatric patients with
      chronic ulcerative colitis: incidence, treatment, and outcomes.
AB  - PURPOSE: Children with chronic ulcerative colitis (CUC) are at increased risk for
      venous thromboembolism, especially after colectomy procedures. We aim to review
      our patients with CUC who underwent a colectomy and suffered intra-abdominal
      thrombosis; moreover we wanted to define thrombotic incidence and outcomes
      METHODS: In this is IRB approved retrospective study, we reviewed our patients
      who underwent colectomy for CUC from January 1999 to December 2011 for
      development of intra-abdominal thrombosis. RESULTS: Of 366 patients with CUC who
      underwent colectomy, 15 (4%) were diagnosed with a venous thromboembolism. All
      patients presented with acute abdominal pain. The locations of thrombus formation
      varied: 13 (87%) developed thrombi in the portal vein, 4 (27%) in the splenic
      vein, 2 (13%) in the superior mesenteric vein, 1 (7%) in the hepatic vein, and 1
      (7%) in the hepatic artery. The mean number of post-operative days at diagnosis
      of thrombus was 38.7 days (range 3-180 days). Fourteen patients (93%) underwent
      anticoagulation for treatment. The mean number of days of anticoagulant therapy
      until documented resolution of thrombus on imaging was 96.3 days (range 14-364
      days). All thrombi resolved with therapy. There was no mortality during follow
      up. CONCLUSIONS: Four percent of our pediatric patients with chronic ulcerative
      colitis who underwent colectomy developed symptomatic intra-abdominal venous
      thromboembolism. 3 to 6 months of anticoagulant therapy is adequate treatment in
      almost all patients. Practitioners should have a high index of suspicion for
      intra-abdominal venous thrombus when these patients complain of abdominal pain
      postoperatively. Based on our experience, prophylactic anticoagulation should be
      strongly considered peri-operatively in this population.

PMID- 24726124
TI  - Endoscopic-assisted surgery for pyriform sinus fistula in children: experience of
      165 cases from a single institution.
AB  - BACKGROUND: Congenital pyriform sinus fistula (PSF) is relatively rare, but often
      presents diagnostic and therapeutic challenges. Herein, we report our experience
      of endoscopic-assisted surgery of PSF in children. METHODS: Since 1999, 165
      children (100 males, 65 females) with PSF had been enrolled. Their clinical
      manifestations were recurrent lateral neck infection, cervical mass and
      respiratory distress. Preoperative investigations included barium swallow,
      ultrasound, computed tomography, and thyroid scan. After resolution of the
      infection, the fistulas were identified by the endoscopic-assisted technique at
      operation. The fistula tract was completely excised just at the apex of the
      pyriform sinus. More recently, the anatomic point where the fistula tract
      penetrated into the pharynx was specified and recorded. RESULTS: Of the 165
      cases, the male to female ratio was 1.54:1, the median age of onset was 3.2 years
      (range, 1 day to 13.8 years), and median age at operation was 5.0 years (range,
      17 days to 15.0 years). One hundred fifty-six (94.6%) fistulas located on the
      left side, 7 right, and 2 bilateral. Twelve neonates and young infants (younger
      than 3 months) presented with a large cervical cyst. The fistulas were completely
      excised in all but 2 (98.8%) with intraoperative gastroscopy successfully
      conducted in 160 cases (97.0%). In 77 cases the points where fistulas penetrated
      into the pharynx were specified intraoperatively, which were classified into 3
      types according to their anatomic relationship with the inferior cornu of the
      thyroid cartilage (ICTC): type I (anterior to ICTC), 22 cases (28.5%); type II
      (inferior to ICTC), 18 cases (23.4%); and type III (posterior to ICTC), 37 cases
      (48.1%). Postoperatively, 160 cases recovered well without complications. PSF
      recurred in 5 cases, 2 of whom were cured by fistula re-excision and 3 remained
      asymptomatic. Esophageal perforation was found and repaired uneventfully in 1
      neonate and 1 young infant. Transient postoperative hoarseness happened in 1
      neonate. All the latter 3 cases had cervical cysts. CONCLUSIONS: To our
      knowledge, this series is the largest report of PSF in children. Our results
      suggested that PSF is more common in males. With the help of endoscopy and a
      better understanding of the anatomic relationship between ICTC and the points
      where the fistulas penetrated into the pharynx, PSF excision can be done
      successfully with minimized complications. For neonates and young infants with a
      cervical cyst, however, the management of PSF continues to be a challenge.

PMID- 24726125
TI  - A novel stop mutation in the EDNRB gene in a family with Hirschsprung's disease
      associated with multiple sclerosis.
AB  - PURPOSE: We identified a girl with Hirschsprung's disease (HSCR) whose mother and
      grandmother had HSCR associated with multiple sclerosis (MS). The aim of this
      study was to outline mutations in HSCR-related genes and MS susceptibility
      alleles in these three individuals. METHODS: The phenotypes were reviewed based
      on medical records. The three subjects had rectosigmoid HSCR verified with
      histopathology. The mother and grandmother fulfilled the McDonald criteria for
      MS. DNA was isolated from EDTA-preserved blood according to standard procedures.
      Exome sequencing aiming mainly at analyzing HSCR associated genes as well as
      Sanger sequencing for confirmation was performed. RESULTS: All affected
      individuals carry a novel heterozygous nonsense mutation in the EDNRB gene
      (c.C397T,p.R133X,refNM_000115), changing an arginine at position 133 into a
      premature stop codon. None of the subjects were homozygous for the HLA risk
      alleles for MS. CONCLUSION: We report a novel non-sense EDNRB gene mutation in a
      girl with HSCR and her mother and grandmother with HSCR and MS. We propose that
      this EDNRB gene mutation plays a role in the etiology of HSCR and also makes the
      subjects susceptible to MS.

PMID- 24726126
TI  - Cholecystectomy in Danish children--a nationwide study.
AB  - BACKGROUND: An increase in the frequency of cholecystectomy in children has been
      described during the last decades. Part of the reason is that more
      cholecystectomies in children are performed for dyskinesia of the gallbladder and
      not only for gallstone disease. We conducted the first nationwide study to
      describe outcome of cholecystectomies performed in children in Denmark by using
      data from the national Danish Cholecystectomy Database (DCD). METHODS: In the
      DCD, two data sources were combined: administrative data from the National
      Patient Registry (NPR) and clinical data entered into the secure Web site by the
      surgeon immediately after the operation. In the present analysis, we have
      included children <= 15 years from the five year period January 1, 2006, to
      December 31, 2010. RESULTS: In the study period 35,444 patients were operated
      with a cholecystectomy. Of these, 196 (0.5%) were <= 15 years. The median age was
      14 years, and 82% were girls. Predisposing medical factors for gallstones
      (despite obesity) were found in only 5%. More than 50% were overweight, and one
      third were obese. Ninety-seven percent of the operations were completed
      laparoscopically, and the conversion rate was 0. 5%. Nearly half of the
      operations (45%) were performed as same day surgery, and 80% of the children
      stayed in hospital 0-1 day without readmission. 91% were discharged within 3 days
      and not readmitted. Morbidity was low, and no bile duct lesions occurred. The 30
      day mortality was zero. CONCLUSION: Our nationwide outcome results indicate good
      quality with 91% of the patients discharged within 3 days without readmission, no
      bile duct injuries, and no mortality. All patients except two were operated for
      symptomatic gallstone disease in accordance to the Danish national guidelines. We
      have not experienced a demand or a need to expand the indications for
      cholecystectomy beyond gallstone disease.

PMID- 24726128
TI  - Innovation in pediatric surgery: the surgical innovation continuum and the
      ETHICAL model.
AB  - Innovations are indispensable to the practice and advancement of pediatric
      surgery. Children represent a special type of vulnerable population and must be
      protected since they do not have legal capacity to consent, and their parent's
      judgment may be compromised in circumstances when the child is very ill or no
      adequate therapy exists. In an effort to protect patients, legislators could pass
      and enforce laws that prohibit or curtail surgical innovations and thus stifle
      noble advancement of the practice. The goals of this paper are, 1) To clearly
      define the characteristics of surgical innovation types so interventions may be
      classified into 1 of 3 distinct categories along a continuum: Practice Variation,
      Transition Zone, and Experimental Research, and 2) To propose a practical
      systematic method to guide surgeon decision-making when approaching interventions
      that fall into the "Transition Zone" category on the Surgical Intervention
      Continuum. The ETHICAL model allows those that know the intricacies and nuances
      of pediatric surgery best, the pediatric surgeons and professional pediatric
      surgical societies, to participate in self-regulation of innovation in a manner
      that safeguards patients without stifling creativity or unduly hampering surgical
      progress. 

PMID- 24726127
TI  - Long-term health-related quality of life after complex and/or complicated
      esophageal atresia in adults and children registered in a German patient support
      group.
AB  - BACKGROUND: Health-related quality of life (HRQoL) after esophageal atresia (EA)
      repair is postulated to be good. However, little is known about the long-term
      results after repair of complex and/or complicated EA regarding HRQoL. We
      investigated long-term HRQoL after delayed anastomosis, esophageal replacement,
      major revisions, or multiple dilatations in patients registered in a support
      group. METHODS: Patients registered in the German patient support group database
      (KEKS) were enrolled and allocated to subgroups according to surgical treatment
      and age. HRQoL was evaluated using validated questionnaires (GIQLI, WHO-5,
      KIDSCREEN27). RESULTS: Complete follow-up (mean 14.5 +/- 9.8 years) was available
      for 90/92 patients. Patients were allocated to subgroups delayed anastomosis
      (n=28), esophageal replacement (n=27), major revisions (n=15), and multiple
      dilatations (n=20). Adult patients presented with impaired well-being according
      to WHO-score and gastrointestinal function (GIQLI). In contrast, HRQoL of
      children was comparable to controls in most KIDSCREEN27-dimensions. Delayed
      anastomosis was associated with most-favourable HRQoL. Regarding physical well
      being, these children scored significantly better than controls [64.01 +/- 10.40
      vs. 52.36 +/- 8.73;p=0.0011], children after replacement [51.40 +/-
      5.70;p=0.008], revisions [52.04 +/- 6.97;p=0.026], and multiple dilatations
      [50.22 +/- 9.67,p=0.04]. CONCLUSIONS: HRQoL after complex and/or complicated EA
      is excellent in children registered in a patient support group. In adults,
      disease-specific symptoms negatively affect HRQoL. Our data indicate that saving
      the esophagus may achieve the best HRQoL.

PMID- 24726129
TI  - Meta analysis of robot-assisted versus conventional laparoscopic fundoplication
      in children.
AB  - BACKGROUND: Minimally invasive fundoplication may be performed using either a
      robot-assisted (RF) or conventional laparoscopic (LF) technique. Evidence
      comparing RF and LF in children remains unclear. This study aims to elucidate the
      comparative safety and efficacy of RF versus LF by systematic review and meta
      analysis. METHODS: Comparative studies investigating RF versus LF in children
      were identified from multiple electronic literature databases. Meta-analysis was
      performed using random effects modeling. Safety parameters investigated were post
      operative morbidity and intra-operative conversions. Efficacy outcomes of
      interest were operative success, re-operation, post-operative complications,
      length of hospital stay (LOS), total operating time (OT), analgesia requirement,
      and cost. RESULTS: Six observational studies met inclusion criteria, reporting
      outcomes of 297 children. No randomized controlled trials were identified. Pooled
      analysis determined no statistically significant differences between RF and LF
      for conversions, OT, LOS, and post-operative complications. There was no
      standardized follow up beyond the early post-operative period to enable data
      synthesis for remaining outcomes of interest. Limited evidence indicates higher
      costs with RF. CONCLUSIONS: Safety and short-term efficacy seem comparable
      between RF and LF in children. There is insufficient evidence to assess
      comparative effectiveness for many important procedure specific outcome measures.
      Higher quality and longer follow-up studies are required.

PMID- 24726130
TI  - Non-pigmented melanoma with nodal metastases masquerading as pyogenic granuloma
      in a 1-year old.
AB  - Malignant melanomas are the most common skin cancer in the pediatric population.
      Melanoma incidence is extremely low in infants, and metastatic disease is even
      less common. We present the case of an 11-month-old girl who presented with a non
      pigmented lesion that progressed to an ulcerated lesion. Pathology was found to
      be Spitzoid melanoma of 7.6-mm thickness. Micrometastases were found on
      examination of the sentinel lymph node. The family chose expectant observation
      following the excision procedure. A pediatric melanoma registry may be helpful in
      developing future analyses of incidence in survival in this specialized
      population. 

PMID- 24726131
TI  - Creation of an appendicovesicostomy Mitrofanoff from a preexisting
      appendicocecostomy utilizing the spilt appendix technique.
AB  - Continent catheterizable channels have revolutionized reconstructive surgery to
      achieve both urinary and fecal continence. The Mitrofanoff and Malone antegrade
      continent catheterizable channels offer improved quality of life relative to
      permanent incontinent stomas. A frequently employed surgical option for creating
      a Mitrofanoff when an existing appendicocecostomy exists involves harvesting a
      separate piece of intestine. If however the Malone has preceded the creation of a
      Mitrofanoff, we describe a surgical technique that may avoid the need for a bowel
      harvest and resultant anastomosis. We report our series of patients utilizing a
      novel alternative strategy in the select clinical circumstance of an existing
      appendicocecostomy to expand the armamentarium of the urologic reconstructive
      surgeon.

PMID- 24726133
TI  - Reply to letter to the editor.

PMID- 24726132
TI  - Technical standardization of laparoscopic lymphatic sparing varicocelectomy in
      children using isosulfan blue.
AB  - PURPOSE: The lymphatic preservation to prevent hydrocele formation after
      laparoscopic varicocelectomy is essential. Lymphatic sparing procedures using
      scrotal injection give a rate of mapping failures of 20%-30%. The aim of the
      present study is to standardize the technique of injection to perform a lymphatic
      sparing procedure in case of laparoscopic varicocelectomy. METHODS: We
      retrospectively evaluated 50 patients who underwent laparoscopic varicocelectomy
      from July 2010 to July 2013. Patients were divided into two groups: G1 (25
      patients) those who underwent a classical isosulfan blue scrotal intra-dartos
      injection and G2 (25 patients) those who underwent the new standardized isosulfan
      blue scrotal intra-dartos/intra-testicular injection. RESULTS: In G1 lymphatic
      vessels were identified as blue coloured in 19/25 of cases (76%), in G2 in 25/25
      of cases (100%). The results were analyzed using test chi(2) with Yates'
      correction and there was a statistically significant difference (chi(2)=0.05,1)
      between G2 and G1. Postoperative hydrocele was noted in 2/6 patients of G1 in
      whom the lymphatic vessels were not identified. CONCLUSIONS: Laparoscopic
      lymphatic sparing varicocelectomy is an effective procedure to adopt in children
      with varicocele. The intra-dartos/intra-testicular injection of isosulfan blue is
      significantly better than the previously described intra-dartos injection,
      permitting to identify lymphatic vessels in 100% of cases in our series. No
      allergy to isosulfan blue was reported in both groups.

PMID- 24726134
TI  - Letter to the editor.

PMID- 24726135
TI  - The influence of anodic helical design on fluid flow and bioelectrochemical
      performance.
AB  - In this study three different tubular helical anode designs are compared, for
      each helical design the pitch and nominal sectional area/liquid flow channel
      between the helicoids was varied and this produced maximum power densities of
      11.63, 9.2 and 6.73Wm(-3) (small, medium and large helical flow channel cross
      sections). It is found that the level of mixing and the associated shear rates
      present in the anodes affects both the power development and biofilm formation.
      The small helical flow channel carbon anode produced 40% more biofilm and this
      result was related to modelling data which determined a system shear rate of
      237s(-1), compared to 52s(-1) and 47s(-1) for the other reactor configurations.
      The results from computational fluid dynamic modelling further distinguishes
      between convective flow conditions and supports the influence of helical
      structure on system performance, so establishing the importance of anodic design
      on the overall electrogenic biofilm activity. 

PMID- 24726136
TI  - The removal of cyanobacteria and their metabolites through anoxic biodegradation
      in drinking water sludge.
AB  - The effects of environmental factors on cyanobacteria damage and microcystin-LR
      degradation in drinking water sludge were investigated under anoxic conditions.
      The rates of microcystin-LR release and degradation increased rapidly with the
      increasing temperature from 15 degrees C to 40 degrees C and the highest
      degradation rate of 99% was observed at 35 degrees C within 10days. Compared to
      acidic conditions, microcystin-LR degraded more rapidly in weak alkali
      environments. In addition, the microbial community structures under different
      anoxic conditions were studied. The sequencing results showed that four phyla
      obtained from the DGGE profiles were as follows: Proteobacteria, Acidobacteria,
      Firmicutes and Cyanobacteria. Proteobacteria containing nine genera were the most
      common species. Pseudomonas, Methylosinus and Sphingomona all showed stronger
      activities and had significant increase as microcystin-LR degraded, so they
      should be responsible for the microcystin-LR degradation. This is the first
      report of Pseudomonas, Methylosinus and Sphingomonas as the microcystins
      degrading microorganisms in anoxic drinking water sludge. 

PMID- 24726137
TI  - Coded waveforms for optimised air-coupled ultrasonic nondestructive evaluation.
AB  - This paper investigates various types of coded waveforms that could be used for
      air-coupled ultrasound, using a pulse compression approach to signal processing.
      These are needed because of the low signal-to-noise ratios that are found in many
      air-coupled ultrasonic nondestructive evaluation measurements, due to the large
      acoustic mismatch between air and many solid materials. The various waveforms,
      including both swept-frequency signals and those with binary modulation, are
      described, and their performance in the presence of noise is compared. It is
      shown that the optimum choice of modulation signal depends on the bandwidth
      available and the type of measurement being made. 

PMID- 24726138
TI  - A curved ultrasonic actuator optimized for spherical motors: design and
      experiments.
AB  - Multi-degree-of-freedom angular actuators are commonly used in numerous
      mechatronic areas such as omnidirectional robots, robot articulations or
      inertially stabilized platforms. The conventional method to design these devices
      consists in placing multiple actuators in parallel or series using gimbals which
      are bulky and difficult to miniaturize. Motors using a spherical rotor are
      interesting for miniature multidegree-of-freedom actuators. In this paper, a new
      actuator is proposed. It is based on a curved piezoelectric element which has its
      inner contact surface adapted to the diameter of the rotor. This adaptation
      allows to build spherical motors with a fully constrained rotor and without a
      need for additional guiding system. The work presents a design methodology based
      on modal finite element analysis. A methodology for mode selection is proposed
      and a sensitivity analysis of the final geometry to uncertainties and added
      masses is discussed. Finally, experimental results that validate the actuator
      concept on a single degree-of-freedom ultrasonic motor set-up are presented. 

PMID- 24726139
TI  - [Days out of role due to common mental and physical disorders: French results
      from the WHO World Mental Health surveys].
AB  - INTRODUCTION: The burden of health problems, including mental disorders, can be
      assessed in several ways such as through healthcare costs or loss of
      productivity. Their impact on daily activities as a whole has received much less
      attention, especially in France. Therefore, we undertook the analysis of the
      French general population data from the World Mental Health (WMH) surveys
      promoted by the World Health Organization (WHO) assessing the number of days out
      of role due to common mental and physical disorders. METHODS: Face-to-face
      interviews were carried out with 2894 respondents (45.9% pooled response rate).
      Presence of ten chronic physical disorders and nine mental disorders was assessed
      for each respondent along with information about the number of days in the past
      month each respondent reported being totally unable to work or carry out their
      other normal daily activities because of problems with either physical or mental
      health. Multiple regression analysis was used to estimate associations of
      specific conditions and comorbidities with days out of role, after controlling
      for basic socio-demographics. RESULTS: One thousand four hundred and thirty-six
      subjects reporting at least one core-symptom of a mental disorder underwent the
      whole assessment. The mean annual number of days out of role was high among those
      with at least one mental disorder (24.2+/-8.3). The population attributable risk
      proportion (PARP), i.e. the proportion of days out of role that would have been
      avoided if the considered disorder had remitted, was also estimated. Mental
      disorders as a whole accounted for 49.5% of the PARP. DISCUSSION: French data on
      days out of role from the WHO WMH surveys showed the high burden of mental
      illness in the general population. These results may have been underestimated,
      taking into account that subjects who were hospitalized at the time of
      recruitment, whose disorders might also account for a high proportion of days out
      of role, could not be assessed with our design. CONCLUSION: Common health
      conditions, especially mental disorders, make up a large proportion of the number
      of days out of role. Such data should be considered to design more efficient
      public health strategies.

PMID- 24726140
TI  - CTHRC1 acts as a prognostic factor and promotes invasiveness of gastrointestinal
      stromal tumors by activating Wnt/PCP-Rho signaling.
AB  - Gastrointestinal stromal tumors (GISTs) are the major gastrointestinal
      mesenchymal tumors with a variable malignancy ranging from a curable disorder to
      highly malignant sarcomas. Metastasis and recurrence are the main causes of death
      in GIST patients. To further explore the mechanism of metastasis and to more
      accurately estimate the recurrence risk of GISTs after surgery, the clinical
      significance and functional role of collagen triple helix repeat containing-1
      (CTHRC1) in GIST were investigated. We found that CTHRC1 expression was gradually
      elevated as the risk grade of NIH classification increased, and was closely
      correlated with disease-free survival and overall survival in 412 GIST patients.
      In vitro experiments showed that recombinant CTHRC1 protein promoted the
      migration and invasion capacities of primary GIST cells. A luciferase reporter
      assay and pull down assay demonstrated that recombinant CTHRC1 protein activated
      noncanonical Wnt/PCP-Rho signaling but inhibited canonical Wnt signaling. The pro
      motility effect of CTHRC1 on GIST cells was reversed by using a Wnt5a
      neutralizing antibody and inhibitors of Rac1 or ROCK. Taken together, these data
      indicate that CTHRC1 may serve as a new predictor of recurrence risk and
      prognosis in post-operative GIST patients and may play an important role in
      facilitating GIST progression. Furthermore, CTHRC1 promotes GIST cell migration
      and invasion by activating Wnt/PCP-Rho signaling, suggesting that the CTHRC1
      Wnt/PCP-Rho axis may be a new therapeutic target for interventions against GIST
      invasion and metastasis. 

PMID- 24726141
TI  - The histone methyltransferase SMYD2 methylates PARP1 and promotes poly(ADP
      ribosyl)ation activity in cancer cells.
AB  - Poly(ADP-ribose) polymerase-1 (PARP1) catalyzes the poly(ADP-ribosyl)ation of
      protein acceptors using NAD(+) as the substrate is now considered as an important
      target for development of anticancer therapy. PARP1 is known to be post
      translationally modified in various ways including phosphorylation and
      ubiquitination, but the physiological role of PARP1 methylation is not well
      understood. Herein we demonstrated that the histone methyltransferase SMYD2,
      which plays critical roles in human carcinogenesis, mono-methylated PARP1. We
      confirmed lysine 528 to be a target of SMYD2-dependent PARP1 methylation by LC
      MS/MS and Edman Degradation analyses. Importantly, methylated PARP1 revealed
      enhanced poly(ADP-ribose) formation after oxidative stress, and positively
      regulated the poly(ADP-ribosyl)ation activity of PARP1. Hence, our study unveils
      a novel mechanism of PARP1 in human cancer through its methylation by SMYD2. 

PMID- 24726142
TI  - Neoadjuvant sorafenib treatment of clear cell renal cell carcinoma and release of
      circulating tumor fragments.
AB  - BACKGROUND: Clear cell renal cell carcinoma (ccRCC) is characterized by high
      constitutive vascular endothelial growth factor A (VEGF-A) production that
      induces a specific vascular phenotype. We previously reported that this phenotype
      may allow shedding of multicellular tumor fragments into the circulation,
      possibly contributing to the development of metastasis. Disruption of this
      phenotype through inhibition of VEGF signaling may therefore result in reduced
      shedding of tumor fragments and improved prognosis. To test this hypothesis, we
      investigated the effect of neoadjuvant sorafenib treatment on tumor cluster
      shedding. PATIENTS AND METHODS: Patients with renal cancer (n = 10, of which 8
      have ccRCC) received sorafenib for 4 weeks before tumor nephrectomy. The
      resection specimens were perfused, and the perfundate was examined for the
      presence of tumor clusters. Effects of the treatment on the tumor morphology and
      overall survival were investigated (follow-up of 2 years) and compared with a
      carefully matched control group. RESULTS: Neoadjuvant sorafenib treatment induced
      extensive ischemic tumor necrosis and, as expected, destroyed the characteristic
      ccRCC vascular phenotype. In contrast to the expectation, vital groups of tumor
      cells with high proliferation indices were detected in postsurgical renal venous
      outflow in 75% of the cases. Overall survival of patients receiving neoadjuvant
      treatment was reduced compared to a control group, matched with regard to
      prognostic parameters. CONCLUSIONS: These results suggest that neoadjuvant
      sorafenib therapy for ccRCC does not prevent shedding of tumor fragments.
      Although this is a nonrandomized study with a small patient group, our results
      suggest that neoadjuvant treatment may worsen survival through as yet undefined
      mechanisms.

PMID- 24726143
TI  - Hyperbaric oxygen for the treatment of diabetic foot ulcers: a systematic review.
AB  - OBJECTIVE: A systematic review of randomized clinical trials (RCTs) to assess the
      additional value of hyperbaric oxygen therapy (HBOT) in promoting the healing of
      diabetic foot ulcers and preventing amputations was performed. METHODS: MEDLINE,
      Embase, and the Cochrane Library were searched to identify RCTs in patients with
      diabetic foot ulcers published up to August 2013. Eligible studies reported the
      effectiveness of adjunctive HBOT with regard to wound healing, amputations, and
      additional interventions. RESULTS: Seven of the 669 identified articles met the
      inclusion criteria, comprising 376 patients. Three trials included 182 patients
      with ischaemic ulcers, two trials studied 64 patients with non-ischaemic ulcers,
      and two trials comprising 130 patients did not specify ulcer type. Two trials
      were of good methodological quality. Pooling of data was deemed inappropriate
      because of heterogeneity. Two RCTs in patients with ischaemic ulcers found
      increased rates of complete healing at 1-year follow-up (number needed to treat
      (NNT) 1.8 (95% CI: 1.1 to 4.6) and 4.1 (95% CI: 2.3 to 19)), but found no
      difference in amputation rates. A third trial in ischaemic ulcers found
      significantly lower major amputation rates in patients with HBOT (NNT 4.2, 95%
      CI: 2.4 to 17), but did not report on wound healing. None of the RCTs in non
      ischaemic ulcers reported differences in wound healing or amputation rates. Two
      trials with unknown ulcer types reported beneficial effects on amputation rates,
      although the largest trial used a different definition for both outcomes. HBOT
      did not influence the need for additional interventions. CONCLUSION: Current
      evidence shows some evidence of the effectiveness of HBOT in improving the
      healing of diabetic leg ulcers in patients with concomitant ischaemia. Larger
      trials of higher quality are needed before implementation of HBOT in routine
      clinical practice in patients with diabetic foot ulcers can be justified.

PMID- 24726144
TI  - Asymptomatic carotid stenosis and cognitive improvement using transcervical
      stenting with protective flow reversal technique.
AB  - OBJECTIVES: The relationship between carotid artery stenosis and cognitive
      function in individuals without a history of stroke is not clear. The possible
      pathomechanisms of cognitive impairment include silent embolization and
      hypoperfusion. In this study the aim was to assess cognitive changes after
      transcervical carotid artery stenting with proximal cerebral protection by flow
      reversal in patients with asymptomatic carotid stenosis, a novel technique that
      has been proved to decrease the number intraoperative emboli. METHODS: 25
      consecutive patients were assessed, of which 22 were men (88%) mean age of 74
      years with severe asymptomatic carotid stenosis who underwent revascularization
      by carotid artery stenting (CAS) with flow reversal. Patients were evaluated 1
      day before and 6 months after the procedure using a standardized
      neuropsychological battery. Test scores were adjusted according to age, sex,
      education level and were standardized (0-100). The mean of all the cognitive
      function scores yielded the global cognitive score (GCS). RESULTS: There were no
      neurological complications during the procedure or during hospitalization in any
      patient. No deaths or cardiac complications occurred in any patient. The pre
      procedure neuropsychological study showed cognitive impairment in: information
      processing speed in 15 patients (62.5%), visuospatial function in 14 (56.0%),
      memory in 18 (72.0%), executive functions in 14 (56.0%), language in three
      (12.0%), attention in 10 (40.0%), and global cognitive performance in eight
      (32.0%). Comparison of these scores with those obtained 6-month post-procedure
      showed significant improvement in GCS in all patients (p = .002), with a
      particularly marked gain in information processing speed (p = .018). Although
      significant improvement was not found for the remaining cognitive functions
      assessed, some gain was documented, and there was no deterioration. CONCLUSIONS:
      Revascularization by transcervical CAS with flow reversal for cerebral protection
      results in improved neurocognitive performance in asymptomatic elderly patients
      with severe carotid artery stenosis.

PMID- 24726145
TI  - Early host tissue response to different types of vascular prostheses coated with
      silver acetate or vaporized metallic silver.
AB  - OBJECTIVES: In vascular surgery, the infection of prosthetic vascular grafts
      represents a serious life-threatening complication. Due to the increasing
      resistance of hospital micro-organisms to standard antibiotic therapies, maximum
      effort should be put in the primary prevention of such infections. For this
      purpose, grafts may be coated with different antibacterial silver formulations.
      In the present study the different effects of silver acetate-coating and
      vaporized metallic silver-coating on the vascularization and perigraft
      inflammation during the initial phase after implantation of Intergard Silver (IS)
      and Silver Graft (SG) were compared. METHODS: Silver acetate-coated IS and
      vaporized metallic silver-coated SG were implanted into the dorsal skinfold
      chamber of C57BL/6 mice (n = 8 per group) to study angiogenesis and leukocyte
      inflammation at the implantation site by means of repetitive intravital
      fluorescence microscopy over a 14-day period. At the end of the in vivo
      experiments, apoptosis and cell proliferation in the newly developed granulation
      tissue surrounding the implants was analyzed by immunohistochemistry. RESULTS: IS
      exhibited an improved vascularization, resulting in a significantly higher
      functional capillary density when compared to SG. Moreover, the leukocyte
      inflammatory response to IS was less pronounced, as indicated by a reduced number
      of adherent leukocytes in perigraft venules. This was associated with a higher
      proliferative activity of the granulation tissue incorporating the IS when
      compared to SG. The numbers of apoptotic cells in the perigraft tissue were low
      and did not differ between the two groups. CONCLUSION: Silver acetate-coated IS
      exhibits an improved vascularization and reduced perigraft inflammation during
      the first 14 days after implantation when compared to vaporized metallic silver
      coated SG. This may contribute to reducing the risk of early perigraft seroma
      formation and subsequent infection.

PMID- 24726146
TI  - Editorial comment.

PMID- 24726147
TI  - Reply: To PMID 24726146.

PMID- 24726148
TI  - Gross hematuria and urinary retention among men from a nationally representative
      survey in Sierra Leone.
AB  - OBJECTIVE: To estimate the prevalence of gross hematuria and urinary retention
      among men in Sierra Leone and report on barriers to care and associated
      disability. Gross hematuria and urinary retention are classic urologic complaints
      that require medical attention for significant underlying pathology, but their
      burden has not been quantified in a developing country. METHODS: A cluster
      randomized, cross-sectional household survey was administered in Sierra Leone
      using the Surgeons OverSeas Assessment of Surgical need tool as a verbal head-to
      toe examination. A total of 2 respondents in each of 25 households in 75 clusters
      were surveyed to assess surgical needs. Data on questions related to blood from
      the penis and the inability to urinate for men>12 years were included in the
      present analysis to determine the period and point prevalence of hematuria and
      urinary retention. RESULTS: From 3645 total respondents, 1054 (28.9%) were men>12
      years included in the analysis. Period and point prevalence of gross hematuria
      were 21.8 per 1000 (95% confidence interval [CI] 13.0-30.7) and 12.3 per 1000
      (95% CI 5.7-19.0), respectively, and for urinary retention, they were 19.9 per
      1000 (95% CI 11.5-28.4) and 4.7 per 1000 (95% CI 0.5-8.9), respectively. Lack of
      financial resources was the major barrier to care. Disability assessment showed
      19.1% were not able to work as a result of urinary retention, and 34.8% felt
      ashamed of their gross hematuria. CONCLUSION: The results provide a prevalence
      estimate of gross hematuria and urinary retention for men in Sierra Leone.
      Accessible medical and surgical care will be critical for early intervention and
      management.

PMID- 24726149
TI  - Weight gain on androgen deprivation therapy: which patients are at highest risk?
AB  - OBJECTIVE: To identify factors associated with weight gain at 1 year from
      initiation of androgen deprivation therapy (ADT). METHODS: A retrospective review
      assessed weight change among 118 men with nonmetastatic prostate cancer treated
      with ADT for at least 6 months. Outcome associations were tested using 2-tailed t
      tests and linear regression. RESULTS: Men in our cohort had significant weight
      gain (+1.32 kg, P=.0005) in the 1 year after ADT initiation. Three risk factors
      for weight gain on ADT were identified as follows: age<65 years (2.72 kg gained,
      P=.001), body mass index (BMI)<30 (1.98 kg gained, P=.00002), and nondiabetic
      status (1.56 kg gained, P=.0003). Multivariable regression found both age<65
      years (beta=4.01, P=.02) and BMI<30 (beta=3.57, P=.03) to be independently
      predictive of weight gain, whereas nondiabetic status was nonsignificantly
      predictive of weight gain (beta=2.14, P=.29). Weight change was further
      stratified by the total number of risk factors present (risk score): scores of 0,
      1, 2, and 3 risk factors corresponded to weight changes of -1.10, +0.41, +1.34,
      and +3.79 kg, respectively (P-trend=.0005). CONCLUSION: Age<65 years and BMI<30
      were both independently associated with weight gain 1 year after starting ADT.
      Increasing weight gain was also strongly associated with increasing number of
      baseline risk factors present. Despite traditional concerns about ADT in
      unhealthy men, these data suggest younger, healthier patients may be at higher
      risk for gaining weight on ADT and should be counseled accordingly.

PMID- 24726150
TI  - A novel technique for endoscopic management of stones in a continent urinary
      reservoir.
AB  - Urinary stones are a well-established complication of lower urinary tract
      reconstruction in children and can be managed through an open, percutaneous, or
      transurethral endoscopic approach for their surgical removal. For children with
      no urethral access, it is not generally advised to pursue an endoscopic approach
      through a catheterizable channel. In this study, we describe a safe and effective
      technique for the endoscopic management of stones through a catheterizable
      channel in a child with a continent urinary reservoir. 

PMID- 24726151
TI  - Practice patterns of urologists in managing Korean men aged 40 years or younger
      with high serum prostate-specific antigen levels.
AB  - OBJECTIVE: To investigate the practice patterns of urologists in managing Korean
      men aged 40 years or younger with high serum prostate-specific antigen (PSA).
      MATERIALS AND METHODS: Data were collected from general health screenings
      conducted at 4 university hospitals between 2004 and 2012. Eligibility criteria
      were Korean men aged<=40 years who were seen by urologists for high PSA (>2.5
      ng/mL). After excluding individuals with chronic prostatitis and any infectious
      symptoms and/or signs, the practice patterns of urologists managing 237 eligible
      men were analyzed. RESULTS: The most common practice was observation after
      antibiotics (40.5%), followed by reassurance (38.4%), prostate biopsy (PBx) after
      antibiotics (11.8%), PBx after PSA follow-up (7.6%), and immediate PBx (1.7%).
      Antibiotics were prescribed empirically to 124 patients (52.3%). Of the entire
      patients, 145 of 237 (61.2%) had at least 1 follow-up PSA, and the follow-up PSA
      with median interval of 43 days (interquartile range, 26-149) was higher than
      initial PSA in 66 of 145 (45.5%). Of the 98 patients undergoing follow-up PSA
      after initial antibiotic treatment, 53 (54.1%) experienced a decline in PSA,
      whereas 45 (45.9%) experienced a rise in PSA. PBx was performed in 50 of 237
      (21.1%), and only a single case (2%) of prostate cancer was diagnosed.
      CONCLUSION: In managing men<=40 years with high PSA, the most common practice
      pattern was observation after antibiotic treatment despite lack of evidences.
      Furthermore, 1 in 5 urologists performed PBx to rule out cancer. Given the very
      low prevalence of cancer in this age group, clear guidelines are needed for
      appropriate management and consistency of care.

PMID- 24726152
TI  - Diagnosis of varicoceles in men undergoing vasectomy may lead to earlier
      detection of hypogonadism.
AB  - OBJECTIVE: To determine the temporal relationship between vasectomy, varicocele,
      and hypogonadism diagnosis. Many young men undergo their first thorough
      genitourinary examination in their adult lives at the time of vasectomy
      consultation, providing a unique opportunity for diagnosis of asymptomatic
      varicoceles. Varicoceles have recently been implicated as a possible reversible
      contributor to hypogonadism. Hypogonadism may be associated with significant
      adverse effect, including decreased libido, impaired cognitive function, and
      increased cardiovascular events. Early diagnosis and treatment of hypogonadism
      may prevent these adverse sequelae. METHODS: Data were collected from the Truven
      Health Analytics MarketScan database, a large outpatient claims database. We
      reviewed records between 2003 and 2010 for male patients between the ages of 25
      and 50 years with International Classification of Diseases, Ninth Revision codes
      for hypogonadism, vasectomy, and varicocele, and queried dates of first claim.
      RESULTS: A total of 15,679 men undergoing vasectomies were matched with 156,790
      men with nonvasectomy claims in the same year. Vasectomy patients were diagnosed
      with varicocele at an earlier age (40.9 vs 42.5 years; P=.009). We identified
      224,817 men between the ages of 25 and 50 years with a claim of hypogonadism, of
      which 5883 (2.6%) also had a claim of varicocele. Men with hypogonadism alone
      were older at presentation compared with men with an accompanying varicocele
      (41.3 [standard deviation+/-6.5] vs 34.9 [standard deviation+/-6.1]; P<.001).
      CONCLUSION: Men undergoing vasectomies are diagnosed with varicoceles at a
      younger age than age-matched controls. Men with varicoceles present with
      hypogonadism earlier than men without varicoceles. Earlier diagnosis of
      varicocele at the time of vasectomy allows for earlier detection of hypogonadism.

PMID- 24726153
TI  - Desert ants locate food by combining high sensitivity to food odors with
      extensive crosswind runs.
AB  - Desert ants feeding on dead arthropods forage for food items that are distributed
      unpredictably in space and time in the food-scarce terrain of the Saharan salt
      pans [1]. Scavengers of the genus Cataglyphis forage individually and do not lay
      pheromone trails [2]. They rely primarily on path integration [3] for navigation
      and, in addition, use visual [4] and olfactory cues [5-7]. While most studies
      have focused on the navigational mechanisms of ants targeting a familiar place
      like the nest or a learned feeding site, little is known about how ants locate
      food in their natural environment. Here we show that Cataglyphis fortis is highly
      sensitive to and attracted by food odors, especially the necromone linoleic acid,
      enabling them to locate tiny arthropods over several meters in distance.
      Furthermore, during the search for food, ants use extensive crosswind walks that
      increase the chances of localizing food plumes. By combining high sensitivity
      toward food odors with crosswind runs, the ants efficiently screen the desert for
      food and hence reduce the time spent foraging in their harsh desert environment. 

PMID- 24726154
TI  - A Paleozoic stem group to mite harvestmen revealed through integration of
      phylogenetics and development.
AB  - Successfully placing fossils in phylogenies is integral to understanding the tree
      of life. Crown-group Paleozoic members of the arachnid order Opiliones are
      indicative of ancient origins and one of the earliest arthropod
      terrestrialization events [1, 2]. Opiliones epitomize morphological stasis, and
      all known fossils have been placed within the four extant suborders [3-5]. Here
      we report a Carboniferous harvestman species, Hastocularis argusgen. nov., sp.
      nov., reconstructed with microtomography (microCT). Phylogenetic analysis
      recovers this species, and the Devonian Eophalangium sheari, as members of an
      extinct harvestman clade. We establish the suborder Tetrophthalmi subordo nov.,
      which bore four eyes, to accommodate H. argus and E. sheari, the latter
      previously considered to be a phalangid [6-9]. Furthermore, embryonic gene
      expression in the extant species Phalangium opilio demonstrates vestiges of
      lateral eye tubercles. These lateral eyes are lost in all crown-group Phalangida,
      but are observed in both our fossil and outgroup chelicerate orders. These data
      independently corroborate the diagnosis of two eye pairs in the fossil and
      demonstrate retention of eyes of separate evolutionary origins in modern
      harvestmen [10-12]. The discovery of Tetrophthalmi alters molecular divergence
      time estimates, supporting Carboniferous rather than Devonian diversification for
      extant suborders and directly impacting inferences of terrestrialization history
      and biogeography. Multidisciplinary approaches integrating fossil and
      neontological data increase confidence in phylogenies and elucidate evolutionary
      history. 

PMID- 24726155
TI  - Global distribution and conservation of evolutionary distinctness in birds.
AB  - BACKGROUND: Integrated, efficient, and global prioritization approaches are
      necessary to manage the ongoing loss of species and their associated function.
      "Evolutionary distinctness" measures a species' contribution to the total
      evolutionary history of its clade and is expected to capture uniquely divergent
      genomes and functions. Here we demonstrate how such a metric identifies species
      and regions of particular value for safeguarding evolutionary diversity. RESULTS:
      Among the world's 9,993 recognized bird species, evolutionary distinctness is
      very heterogeneously distributed on the phylogenetic tree and varies little with
      range size or threat level. Species representing the most evolutionary history
      over the smallest area (those with greatest "evolutionary distinctness rarity")
      as well as some of the most imperiled distinct species are often concentrated
      outside the species-rich regions and countries, suggesting they may not be well
      captured by current conservation planning. We perform global cross-species and
      spatial analyses and generate minimum conservation sets to assess the benefits of
      the presented species-level metrics. We find that prioritizing imperiled species
      by their evolutionary distinctness and geographic rarity is a surprisingly
      effective and spatially economical way to maintain the total evolutionary
      information encompassing the world's birds. We identify potential conservation
      gaps in relation to the existing reserve network that in particular highlight
      islands as effective priority areas. CONCLUSIONS: The presented distinctness
      metrics are effective yet easily communicable and versatile tools to assist
      objective global conservation decision making. Given that most species will
      remain ecologically understudied, combining growing phylogenetic and spatial data
      may be an efficient way to retain vital aspects of biodiversity.

PMID- 24726156
TI  - Programmed cell death controlled by ANAC033/SOMBRERO determines root cap organ
      size in Arabidopsis.
AB  - BACKGROUND: The root cap is a plant organ that ensheathes the meristematic stem
      cells at the root tip. Unlike other plant organs, the root cap shows a rapid
      cellular turnover, balancing constant cell generation by specific stem cells with
      the disposal of differentiated cells at the root cap edge. This cellular turnover
      is critical for the maintenance of root cap size and its position around the
      growing root tip, but how this is achieved and controlled in the model plant
      Arabidopsis thaliana remains subject to contradictory hypotheses. RESULTS: Here,
      we show that a highly organized cell death program is the final step of lateral
      root cap differentiation and that preparation for cell death is transcriptionally
      controlled by ANAC033/SOMBRERO. Precise timing of cell death is critical for the
      elimination of root cap cells before they fully enter the root elongation zone,
      which in turn is important in order to allow optimal root growth. Root cap cell
      death is followed by a rapid cell-autonomous corpse clearance and DNA
      fragmentation dependent on the S1-P1 type nuclease BFN1. CONCLUSIONS: Based on
      these results, we propose a novel concept in plant development that recognizes
      programmed cell death as a mechanism for maintaining organ size and tissue
      homeostasis in the Arabidopsis root cap.

PMID- 24726157
TI  - Stimulus salience as an explanation for imperfect mimicry.
AB  - The theory of mimicry explains how a mimic species gains advantage by resembling
      a model species [1-3]. Selection for increased mimic-model similarity should then
      result in accurate mimicry, yet there are many surprising examples of poor
      mimicry in the natural world [4-8]. The existence of imperfect mimics remains a
      major unsolved conundrum. We propose and experimentally test a novel explanation
      of the phenomenon. We argue that predators perceive prey as having several
      traits, but that the traits differ in their importance for learning. When
      predators learn to discriminate prey, high-salience traits overshadow other
      traits, leaving them under little or no selection for similarity, and allow
      imperfect mimicry to succeed. We tested this idea experimentally, using blue tits
      as predators and artificial prey with three prominent traits: color, pattern, and
      shape. We found that otherwise imperfect color mimics were avoided about as much
      as perfect mimics, whereas pattern and shape mimics did not gain from their
      similarity to the model. All traits could separately be perceived and learned by
      the predators, but the color trait was learned at a higher rate, implying that it
      had higher salience. We conclude that difference in salience between components
      of prey appearance is of major importance in explaining imperfect mimicry. VIDEO
      ABSTRACT: 

PMID- 24726158
TI  - Editorial overview: virus structure and function.

PMID- 24726159
TI  - Effects of mitomycin-C on tear film, corneal biomechanics, and surface
      irregularity in mild to moderate myopic surface ablation: preliminary results.
AB  - PURPOSE: To assess the effect of mitomycin-C (MMC) on the tear film, corneal
      biomechanics, and surface irregularity in surface ablation (photorefractive
      keratectomy [PRK]) for low to moderate myopia. SETTING: Refractive Surgery Unit,
      Farabi Eye Hospital, Tehran, Iran. DESIGN: Double-masked randomized clinical
      trial. METHODS: In patients with spherical equivalent myopia of -0.75 to -3.87
      diopters (D) and astigmatism up to -1.75 D, the first eye was randomly assigned
      to the application of MMC 0.02% or a balanced salt solution for 15 seconds. The
      fellow eye received the alternate in a masked fashion after excimer
      photoablation. RESULTS: The study enrolled 60 patients. In fellow eyes, the
      changes in the tear-film index were comparable 1 month and 6 months
      postoperatively. There was no significant difference in changes in total higher
      order aberrations, spherical aberration, coma, or Q values (Pentacam HR) between
      fellow eyes at 1 month and 6 months. There was a trend toward a higher asymmetry
      index at 1 month; however, a statistically significant drop was observed at 6
      months in the MMC group (P<.01). It was hypothesized that stromal remodeling was
      delayed, but better, in MMC-treated eyes. No haze was recorded at 6 months in
      either group. CONCLUSION: Use of MMC in PRK did not appear to contribute
      significantly to surface irregularity, transient tear-film dysfunction, or
      biomechanical weakening of the cornea compared with PRK without MMC. FINANCIAL
      DISCLOSURE: No author has a financial or proprietary interest in any material or
      method mentioned.

PMID- 24726161
TI  - Prognostic contribution of urine osmolality in patients presenting with acute
      heart failure.

PMID- 24726160
TI  - Changes in custom biomechanical variables after femtosecond laser in situ
      keratomileusis and photorefractive keratectomy for myopia.
AB  - PURPOSE: To analyze changes in new biomechanical descriptors with myopic
      femtosecond laser-assisted laser in situ keratomileusis (LASIK), compare them
      with the biomechanical response after photorefractive keratectomy (PRK) with
      similar levels of myopic ablation, and evaluate correlations between changes in
      custom variables and biomechanically relevant variables. SETTING: Cleveland
      Clinic, Cleveland, Ohio, USA. DESIGN: Cohort study. METHODS: Custom biomechanical
      variables from the Optical Response Analyzer were assessed preoperatively and 1
      and 3 months postoperatively. Differences between preoperative values and
      postoperative values were determined. Intraindividual change (preoperative value
      minus postoperative value) was calculated and compared with changes after PRK.
      The correlation of the change in each custom biomechanical variable with the
      preoperative central corneal thickness, residual stromal bed tissue ablated, and
      percentage of tissue depth altered was also studied. RESULTS: The study enrolled
      156 eyes of 156 consecutive patients. Fifteen variables changed significantly
      after femtosecond myopic LASIK and were stable postoperatively because no
      significant difference was shown between 1-month values and 3-month values.
      Comparison of the changes in biomechanical variables between LASIK and PRK eyes
      showed no significant differences. Surgical changes in several custom
      biomechanical variables correlated with the percentage of tissue depth altered.
      CONCLUSIONS: The results provide the first reference values for a more
      comprehensive panel of indicators of the biomechanical response to myopic LASIK
      and PRK. Changes in custom variables reflected a consistent decrease in corneal
      biomechanical resistance to deformation after myopic femtosecond LASIK and PRK.
      For comparable attempted corrections, biomechanical changes were comparable
      between femtosecond laser-assisted LASIK and PRK. FINANCIAL DISCLOSURE(S):
      Proprietary or commercial disclosures are listed after the references.

PMID- 24726163
TI  - NOBORITM biodegradable-polymer biolimus-eluting stent versus durable-polymer drug
      eluting stents: a meta-analysis.

PMID- 24726162
TI  - Pharmacodynamic efficacy and safety of adjunctive cilostazol loading to
      clopidogrel and aspirin loading: the results of the ACCEL-LOADING (Accelerated
      Platelet Inhibition by Cilostazol Loading) study.

PMID- 24726164
TI  - Simvastatin dose and risk of rhabdomyolysis: nested case-control study based on
      national health and drug dispensing data.
AB  - BACKGROUND: Two randomised controlled trials have found a higher risk of
      rhabdomyolysis in users of 80 mg versus 20 mg simvastatin, but there is very
      limited information about the risk associated with other doses. We undertook a
      nested case-control study, using routinely collected national health and drug
      dispensing data, to estimate the relative and absolute risks of rhabdomyolysis
      resulting in hospital admission or death according to simvastatin dose. METHODS
      AND RESULTS: The underlying study cohort comprised all patients (n=313,552) who
      initiated a new episode of simvastatin use in New Zealand between 1 May 2005 and
      31 December 2009. Cases (n=29) were patients with a diagnosis of rhabdomyolysis
      after cohort entry, confirmed by hospital discharge letter or death records. Ten
      controls, matched by year of birth and sex, were randomly selected from the study
      cohort using risk set sampling. Current users of 40 mg simvastatin daily were
      about five times as likely to develop rhabdomyolysis as those taking 20mg; the
      adjusted odds ratio was 5.3 (95% CI 1.9-15.0). The absolute excess risk of
      rhabdomyolysis associated with the use of 40 mg versus 20mg was about 10 per
      100,000 person-years; the crude incidence rates were 11.5 (95% CI 7.1-17.5) and
      2.1 (95% CI 0.7-4.8) per 100,000 person-years respectively. CONCLUSIONS: These
      findings provide reassurance that the absolute risk of rhabdomyolysis in a
      general population of simvastatin users is very low. Nonetheless, they also raise
      questions about the optimal simvastatin regimen to maximise cardiovascular
      benefits and minimise the risk of serious muscle injury.

PMID- 24726165
TI  - Single, remote-magnetic catheter approach for pulmonary vein isolation in
      patients with paroxysmal and non-paroxysmal atrial fibrillation.
AB  - BACKGROUND: The aim of the study was to investigate the safety and efficacy of a
      single, remote-magnetic catheter navigation system (MNS) for pulmonary vein
      isolation (PVI). METHODS: A total of 107 PVI procedures in 71 patients with
      paroxysmal (32%), persistent (38%) and longstanding-persistent (30%) atrial
      fibrillation (AF) were analyzed. A wide area circumferential radiofrequency
      ablation PVI was performed with either an 8mm MNS (first 35 procedures) or an
      irrigated MNS (last 36 procedures) catheter. Electrical isolation was confirmed
      with circular pacing/sensing using the MNS catheter and a coronary sinus
      catheter. Our follow-up strategy in the first year and upon symptoms thereafter
      was: clinical check plus 12-lead ECG (100%) and 24 h-ECG recordings (76%) at 3
      month intervals, trans-telephonic ECG (79%) twice daily and upon symptoms (4
      weeks every 3 months), or ECG monitoring via implanted devices (9%). RESULTS: The
      mean procedure time at 1st PVI was 247+/-61 min, and mean fluoroscopy time was
      44+/-18 min. The overall complication rate was 2%. Success rates did not differ
      at the 1st PVI regarding catheter type (p=0.931) but were dependent on history of
      AF: patients with paroxysmal AF had the highest success rates of 58% and 29%
      after 1 and 3 years of follow-up, respectively (p=0.0084). CONCLUSION: PVI with a
      single MNS catheter is safe and is associated with short fluoroscopy exposition.
      Despite a rigorous follow-up strategy success rates favorably compare with
      recently published data on hand-held PVI. Thus, multipolar catheters or a 2nd
      trans-septal puncture may not be mandatory.

PMID- 24726166
TI  - Effects of timing, location and definition of reinfarction on mortality in
      patients with totally occluded infarct related arteries late after myocardial
      infarction.
AB  - BACKGROUND: The Occluded Artery Trial (OAT) randomized stable patients
      (n=2201)>24 h (calendar days 3-28) after myocardial infarction (MI) with totally
      occluded infarct-related arteries (IRA), to percutaneous coronary intervention
      (PCI) with optimal medical therapy, or optimal medical therapy alone (MED). PCI
      had no impact on the composite of death, reinfarction, or class IV heart failure
      over extended follow-up of up to 9 years. We evaluated the impact of early and
      late reinfarction and definition of MI on subsequent mortality. METHODS AND
      RESULTS: Reinfarction was adjudicated according to an adaptation of the 2007
      universal definition of MI and the OAT definition (>=2 of the following-
      symptoms, EKG and biomarkers). Cox regression models were used to analyze the
      effect of post-randomization reinfarction and baseline variables on time to
      death. After adjustment for baseline characteristics the 169 (PCI: n=95; MED:
      n=74) patients who developed reinfarction by the universal definition had a 4.15
      fold (95% CI 3.03-5.69, p<0.001) increased risk of death compared to patients
      without reinfarction. This risk was similar for both treatment groups
      (interaction p=0.26) and when MI was defined by the stricter OAT criteria.
      Reinfarctions occurring within 6 months of randomization had similar impact on
      mortality as reinfarctions occurring later, and the impact of reinfarction due to
      the same IRA and a different epicardial vessel was similar. CONCLUSIONS: For
      stable post-MI patients with totally occluded infarct arteries, reinfarction
      significantly independently increased the risk of death regardless of the initial
      management strategy (PCI vs. MED), reinfarction definition, location and early or
      late occurrence.

PMID- 24726167
TI  - Exercise training leads to physiological left ventricular hypertrophy in COPD.

PMID- 24726168
TI  - Rosuvastatin increases myocardial microvessels in SHR rats. Role of thioredoxin-1
      and peroxiredoxin-2 expression.

PMID- 24726169
TI  - Association between vitamin D status and markers of vascular health in patients
      with chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME).

PMID- 24726170
TI  - Prevalence of risk factors for atrial fibrillation and stroke among 1210 patients
      with sleep disordered breathing.
AB  - AIMS: This study sought to identify the prevalence of risk factors for atrial
      fibrillation and stroke in a sleep apnea population. METHODS: Study participants
      included 1210 consecutive adults who were referred with suspicion of sleep apnea.
      Statistical analysis was used to determine the relationship between sleep apnea
      syndrome and risk factors for atrial fibrillation and stroke. RESULTS: Among 1210
      enrolled patients, 65.8% had severe sleep apnea (Apnea/hypopnea Index--AHI>30),
      25.2% had mild to moderate sleep apnea (AHI 5 to 30), and 8.8% had no sleep apnea
      (AHI<5). At baseline, the mean apnea-hypopnea index in patients with sleep apnea
      syndrome was 35. Compared to patients with an AHI<5, those with an AHI>30 were
      older (47.3+/-11.4 vs. 52.74+/-12.4, p<0.001) and had a higher body mass index
      (BMI) (30.7+/-7.3 vs. 33.83+/-10.1, p<0.001), a higher prevalence of hypertension
      (38 vs. 16%, p<0.001), and a higher CHADS2 (congestive heart failure,
      hypertension, age, diabetes and prior stroke) score (0.59+/-0.8 vs. 0.28+/-0.64,
      p<0.001). CONCLUSIONS: Patients with severe sleep apnea have a higher prevalence
      of risk factors for atrial fibrillation and stroke when compared with subjects
      without sleep apnea.

PMID- 24726171
TI  - Tibia valga morphology in osteoarthritic knees: importance of preoperative full
      limb radiographs in total knee arthroplasty.
AB  - Osteoarthritis of the knee is associated with deformities of the lower limb.
      Tibia valga is a contributing factor to lower limb alignment in valgus knees. We
      evaluated 97 valgus knees and 100 varus knees. Long-leg films were taken in
      weight bearing with both knees in full extension. For valgus knees, 52 knees
      (53%) had a tibia valga deformity. Average tibia valgus deformation was 5.0
      degrees . For varus knees, there was only 1 case of tibia valga (1%), with a
      deformation of 2.5 degrees . The aim of this study was to assess the prevalence
      of primary tibia valga in valgus and varus knees and understand how it affects
      our approach to total knee arthroplasty (TKA). We recommend having full-leg
      length films when planning for TKA in valgus knees. 

PMID- 24726172
TI  - Cemented versus cementless fixation of a tibial component in LCS mobile-bearing
      total knee arthroplasty performed by a single surgeon.
AB  - Although cemented tibial fixation of total knee arthroplasty accepted as the gold
      standard, cementless fixation as a means to supplement disadvantages of cemented
      fixation continues to be of interest to clinicians. One hundred sixty-eight
      consecutive knees undergoing primary knee arthroplasty for osteoarthritis were
      randomly assigned to receive either a cemented (86 knees) or cementless (82
      knees) fixation of tibial component. We report the outcomes at 8 to 11years
      (mean, 9.5). The mean KSS, the HSS score, the mean WOMAC, the mean ranges of knee
      movement and radiological results were similar in both groups. No osteolysis was
      identified in either group. The rate of survival of the femoral and tibial
      components was 100% in both groups at final follow-up.

PMID- 24726173
TI  - Isolated acetabular revision with ceramic-on-ceramic bearings using a ceramic
      head with a metal sleeve.
AB  - The purpose of this study is to evaluate results of isolated acetabular revision
      with ceramic-on-ceramic bearings using a ceramic head with a metal sleeve. A
      retrospective review of fifty-three hips was performed. The mean patient age was
      49.9years and the mean follow-up period was 5.7years. The mean modified Harris
      hip score improved from 47.5, pre-operatively, to 84.7 at the time of last follow
      up (P<0.001). Two patients reported squeaking of the hip. Three patients
      experienced loosening cup, necessitating re-revision surgery. There was a
      significant difference of acetabular bone defect between loose cup group and
      stable cup group (P=0.018). There were no ceramic fractures and no osteolysis.
      The survival rate of the acetabular cup at the mid-term follow-up was 94.3%. In
      conclusion, ceramic head with a metal sleeve can be a reliable option for
      isolated acetabular revision.

PMID- 24726174
TI  - Comparing efficacy of three methods of tranexamic acid administration in reducing
      hemoglobin drop following total knee arthroplasty.
AB  - The ideal method of providing tranexamic acid (TXA) for decreasing hemoglobin
      drop after TKA is still controversial. In this clinical trial, 200 patients were
      randomly allocated to four groups. In group 1,500 mg TXA was administered
      intravenously. In group 2, the joint irrigated with 3 g of TXA in 100 cc of
      saline. In group 3, 1.5 g of TXA was injected through the drain. Group 4 did not
      take TXA. Albeit all methods had a statistical effect on hemoglobin drop,
      drainage and number of transfused units when compared to controls, but
      intravenous injection of TXA seems to be much more effective in terms of reducing
      hemoglobin drop and transfused units; and what's more TXA injection by drain is
      more effective regarding to reducing postoperative drainage.

PMID- 24726175
TI  - Component size mismatch of metal on metal hip arthroplasty: an avoidable never
      event.
AB  - Size mismatch of components used in total hip arthroplasty is a serious,
      preventable patient safety incident of unknown prevalence as many cases are not
      detected. Component size mismatch was found in 11 cases (0.9%) at our retrieval
      centre. All cases of mismatch were not detected on plain radiograph during
      routine clinical follow up and blood metal ion levels were elevated above the
      MHRA action level of 7 ppb. Root cause analysis identified manufacturer, hospital
      and surgeon factors that need to be addressed to reduce the incidence of this
      avoidable clinical problem. Retrieval analysis is the only method of confirming
      size mismatch and is likely to be under-represented in National Joint Registries
      that record the indication for revision at the time of revision.

PMID- 24726176
TI  - Newborn screening: A complex system that requires a culture of safety.
AB  - As health care providers and organizations, we have a responsibility to examine
      our practices and systems for opportunities to improve quality and health
      outcomes. Today a critical opportunity exists in the newborn screening (NBS)
      system, which touches every one of the approximately 4 million babies born
      annually in the United States. This opportunity involves improving the quality of
      NBS by developing a culture of safety to prevent errors that in NBS represent
      missed babies and preventable morbidity and mortality. This commentary will
      explore the "culture of safety" for NBS, including the high reliability
      organization (HRO) paradigm and normal accident theory (NAT), which have been
      effective in reducing systems failures in other complex environments.

PMID- 24726178
TI  - Risk factors for neonatal thyroid dysfunction in pregnancies complicated by
      Graves' disease.
AB  - OBJECTIVE: To determine the factors related to adverse pregnancy outcomes and
      neonatal thyroid dysfunction in pregnancies complicated by Graves' disease. STUDY
      DESIGN: Thirty-five pregnancies complicated by Graves' disease were divided into
      two groups: adverse pregnancy outcome (n=15) and no adverse pregnancy outcome
      (n=20). Adverse pregnancy outcomes included spontaneous abortion, stillbirth,
      premature delivery, fetal growth restriction, and pregnancy-induced hypertension.
      The 31 pregnancies resulting in live births were also divided into two groups:
      neonatal thyroid dysfunction (n=9) and normal neonatal thyroid function (n=22).
      Serum levels of thyroid-stimulating hormone (TSH), free thyroxine (FT4), TSH
      receptor antibody (TRAb), the duration of hyperthyroidism in pregnancy, doses of
      antithyroid medication, and the duration of maternal antithyroid medication
      throughout pregnancy were compared. RESULTS: There were no significant
      differences in these factors between pregnancies with an adverse pregnancy
      outcome and those with no adverse pregnancy outcome. However, serum levels of
      FT4, TRAb, the duration of hyperthyroidism in pregnancy, the maximum daily dose
      of antithyroid medication, and the total dose of antithyroid medication were
      significantly different between pregnancies with neonatal thyroid dysfunction and
      those with normal neonatal thyroid function. Multivariate logistic regression
      analysis showed that the FT4 level in mothers was a significant factor related to
      the development of neonatal thyroid dysfunction (odds ratio 28.84, 95% confidence
      interval 1.65-503.62, p<0.05). CONCLUSION: Graves' disease activity in women of
      childbearing age should be well controlled prior to conception.

PMID- 24726177
TI  - Molecular testing of 163 patients with Morquio A (Mucopolysaccharidosis IVA)
      identifies 39 novel GALNS mutations.
AB  - Morquio A (Mucopolysaccharidosis IVA; MPS IVA) is an autosomal recessive
      lysosomal storage disorder caused by partial or total deficiency of the enzyme
      galactosamine-6-sulfate sulfatase (GALNS; also known as N-acetylgalactosamine-6
      sulfate sulfatase) encoded by the GALNS gene. Patients who inherit two mutated
      GALNS gene alleles have a decreased ability to degrade the glycosaminoglycans
      (GAGs) keratan sulfate and chondroitin 6-sulfate, thereby causing GAG
      accumulation within lysosomes and consequently pleiotropic disease. GALNS
      mutations occur throughout the gene and many mutations are identified only in
      single patients or families, causing difficulties both in mutation detection and
      interpretation. In this study, molecular analysis of 163 patients with Morquio A
      identified 99 unique mutations in the GALNS gene believed to negatively impact
      GALNS protein function, of which 39 are previously unpublished, together with 26
      single-nucleotide polymorphisms. Recommendations for the molecular testing of
      patients, clear reporting of sequence findings, and interpretation of sequencing
      data are provided. 

PMID- 24726179
TI  - Sarcopenia, physical rehabilitation and functional outcomes of patients in a
      subacute geriatric care unit.
AB  - Sarcopenia is the loss of muscle mass and strength, which in the elderly can
      result in disability and affect functional outcomes after hospitalization. The
      aim of this study was to evaluate the functional outcomes and mortality during
      hospitalization and at three months post-discharge, according to the presence of
      sarcopenia. Prospective study of 99 patients (38.4% men, aged 84.6) admitted in a
      subacute geriatric care unit who underwent a rehabilitation intervention. Main
      outcomes were mortality and functional improvement at discharge and at three
      month follow-up. Sarcopenia was assessed by handgrip strength (hydraulic
      dynamometer) and by body composition bioimpedance. Forty-six (46.5%) patients met
      diagnostic criteria of sarcopenia. Patients with sarcopenia had a worse prior
      functional status than those without the condition (Barthel Index: 64.2+/-22.8 vs
      73.3+/-21.8; p=0.04) but both groups had similar functional decline at admission
      (Barthel Index: 24+/-15.1 vs 28.5+/-15.2; p=0.1) and achieved similar functional
      improvement at discharge (20.4+/-18.3 vs 27.4+/-21; p=0.08). Barthel Index at
      discharge remained comparatively worse in patients with sarcopenia (44.2+/-26.6
      vs 55.9+/-26.7; p=0.03). After completing a 3-month at-home rehabilitation
      program, no changes in functional capacity were observed in patients with
      sarcopenia; their peers improved their Barthel Index scores (45.5+/-24.8 vs
      61.6+/-26.6; p=0.007). Mortality rates at 3-month follow-up did not differ
      between groups. In conclusion, patients with sarcopenia had a worse functional
      status, similar functional improvement during hospitalization and a lack of
      recovery after returning home. Further studies are needed to establish long-terms
      effects on mortality. 

PMID- 24726180
TI  - Frequency, severity and determinants of functional limitations in older adults
      with joint pain and comorbidity: results of a cross-sectional study.
AB  - Older adults with joint pain and comorbidity are especially at risk of becoming
      functionally impaired. Therefore, we studied the frequency and severity of
      functional limitations and identified potential modifiable determinants that may
      reduce functional limitations. A prospective cohort study of older adults (>=65
      years) with joint pain and comorbidity provided cross-sectional baseline data
      (n=407). Based on the International Classification of Functioning, Disability and
      Health (ICF) model, we measured Physical Functioning; PF, (Instrumental)
      Activities of Daily Living; (I)ADL, and participation. Apart from examining the
      frequency and severity, we identified determinants of functional limitations with
      multivariate regression analyses, by adding determinants in two steps: (1) only
      physical determinants, (2) physical and psychosocial determinants. Limitations in
      PF, ADL, IADL and participation were present in 66%, 31%, 61% and 47% of the
      participants, respectively. About 22% reported limitations on all four measures.
      Of the physical determinants, especially frailty and higher pain intensity were
      related to functional limitations. Remarkably, adding psychosocial determinants
      to the model weakened some of these relations. The psychosocial determinants were
      especially related to poor PF (i.e. anxiety symptoms, activity avoidance and poor
      general health perception) and participation restrictions (i.e. depressive
      symptoms, less social support). An inverse relation was present between self
      efficacy and both outcomes. In conclusion, our sample reported substantial levels
      of functional limitations. More depressive symptoms, more activity avoidance and
      less social support were indicative of more functional limitations, whereas
      higher perceived self-efficacy was indicative of better functioning. Such
      psychosocial determinants should receive more attention in research. 

PMID- 24726181
TI  - Physical therapy mandates by medicare administrative contractors: effective or
      wasteful?

PMID- 24726182
TI  - Does resident involvement impact post-operative complications following primary
      total knee arthroplasty? An analysis of 24,529 cases.
AB  - Little is known about the impact of resident involvement on complication rates
      following total knee arthroplasty (TKA). The goal of our study was to determine
      the impact of resident involvement on complications following primary TKA. Using
      the American College of Surgeons National Surgical Quality Improvement Program
      (NSQIP) database (2005-2012) we identified 24,529 patients who underwent primary
      TKA. Of these, 5960 (24.3%) had a resident involved in a primary TKA. Using a
      multivariate logistic regression which incorporated propensity score adjustment,
      no differences were seen in morbidity and mortality following those cases with
      resident involvement (OR: 1.15, P = 0.129). In the first large scale,
      comprehensive analysis of resident impact on short-term morbidity and mortality,
      no increase in complications was observed with resident involvement in primary
      TKA.

PMID- 24726183
TI  - Does speed matter? Revision rates and functional outcomes in TKA in relation to
      duration of surgery.
AB  - Longer operative times may be required in complex total knee arthroplasty (TKA),
      however little is known about outcomes in procedures performed rapidly. We
      analysed 58,009 primary TKAs from the New Zealand National Joint Registry. The
      mean surgical duration was 89 minutes, and 50% of procedures lasted between 60
      and 89 minutes. There was no difference in adjusted revision rates for groups
      lasting between 40 and 120 minutes, however procedures lasting >120 minutes had
      significantly higher revision rates. There was a higher revision rate in TKAs
      lasting <40 minutes (0.71 vs 0.48 revisions per 100 component years) but this was
      not statistically significant (P = 0.1). For primary TKAs lasting less than 120
      minutes, further shortening operative time did not improve outcome, and very
      rapid procedures (<40 minutes) may lead to an increased risk of revision.

PMID- 24726184
TI  - Adsorption and removal of phthalic acid and diethyl phthalate from water with
      zeolitic imidazolate and metal-organic frameworks.
AB  - ZIF-8 (zinc-methylimidazolate framework-8), one of the zeolitic imidazolate
      frameworks (ZIFs), has been used for the removal of phthalic acid (H2-PA) and
      diethyl phthalate (DEP) from aqueous solutions via adsorption. The adsorption
      capacity of the ZIF-8 for H2-PA was much higher than that of a commercial
      activated carbon or other typical metal-organic frameworks (MOFs). Because the
      surface area and pore volume of the adsorbents showed no favorable effect on the
      adsorption of H2-PA, the remarkable adsorption with ZIF-8 suggests a specific
      favorable interaction (electrostatic interaction) between the positively charged
      surface of ZIF-8 and the negatively charged PA anions. In addition, acid-base
      interactions also have a favorable contribution in the adsorption of H2-PA, based
      on the adsorptive performances of pristine and amino-functionalized MOFs and
      adsorption over ZIF-8 at acidic condition (pH=3.5). The reusability of ZIF-8 was
      also demonstrated after simple washing with methanol. On the other hand, ZIF-8
      was not effective in adsorbing DEP probably because of little charge of DEP in a
      water solution. 

PMID- 24726185
TI  - Study of pollutant distribution in the Guaxindiba Estuarine System--SE Brazil.
AB  - The Guaxindiba Estuarine System is located in the northeast portion of Guanabara
      Bay. Despite the location inside an environmental protection zone, the main
      affluent of the river runs through the extremely urbanized area of the cities of
      Niteroi and Sao Goncalo. In order to understand the contamination levels of the
      estuary, 35 surface sediment samples were collected along the river and estuarine
      area and analyzed for the presence of heavy metals, PAHs, organochlorated
      pesticides, polychlorinated biphenyl and other contaminants. The analyzed data
      revealed a greatly affected environment with respect to most of these substances.
      The results suggested propitious deposits of contaminants, with high
      concentrations of organic matter and fine sediment. The levels of heavy metal in
      the entire estuarine system were high compared with the local background. The
      total mean concentrations of As, Cd, Pb, Cu, Zn, Hg, Cr and Ni in the surface
      sediments were: 3.74; 0.03; 19.3; 15.0; 99.0; n.d.; 29.0; and 22.0mg/kg,
      respectively, confirming, in certain cases, the high capacity of the environment
      to concentrate pollution. 

PMID- 24726186
TI  - Rivers as a source of marine litter--a study from the SE Pacific.
AB  - Composition and abundance of persistent buoyant litter (plastics, polystyrene and
      manufactured wood) were investigated at riversides and on adjacent coastal
      beaches of four rivers flowing into the SE Pacific Ocean. Persistent buoyant
      litter made up the main share of litter at riversides (36-82%) and on coastal
      beaches near the river mouths (67-86%). The characteristic litter composition of
      each river is attributable to human influences along its course. Riverine litter
      items were deposited to both sides of the river mouths on coastal beaches, and
      their abundance generally declined with distance from the river mouth. However,
      maximum litter accumulations were often found on beaches north of the river
      mouth, suggesting a long-term influence of the prevailing equatorward low-level
      jet along the Chilean coast. The results confirm that riverine transport has an
      important impact on litter abundances on coastal beaches. 

PMID- 24726187
TI  - Er!: eel anyone?

PMID- 24726188
TI  - Risk management for outsourcing biomedical waste disposal - using the failure
      mode and effects analysis.
AB  - Using the failure mode and effects analysis, this study examined biomedical waste
      companies through risk assessment. Moreover, it evaluated the supervisors of
      biomedical waste units in hospitals, and factors relating to the outsourcing risk
      assessment of biomedical waste in hospitals by referring to waste disposal acts.
      An expert questionnaire survey was conducted on the personnel involved in waste
      disposal units in hospitals, in order to identify important factors relating to
      the outsourcing risk of biomedical waste in hospitals. This study calculated the
      risk priority number (RPN) and selected items with an RPN value higher than 80
      for improvement. These items included "availability of freezing devices",
      "availability of containers for sharp items", "disposal frequency", "disposal
      volume", "disposal method", "vehicles meeting the regulations", and "declaration
      of three lists". This study also aimed to identify important selection factors of
      biomedical waste disposal companies by hospitals in terms of risk. These findings
      can serve as references for hospitals in the selection of outsourcing companies
      for biomedical waste disposal. 

PMID- 24726189
TI  - Novel safety floors do not influence early compensatory balance reactions in
      older adults.
AB  - Novel safety flooring systems are a promising approach for reducing fall-related
      injuries in seniors, as they have been demonstrated to substantially reduce
      impact severity during falls, while minimally impairing balance control in
      community-dwelling older women. This pilot study aimed to characterize the
      potential effects of flooring conditions on dynamic balance control in retirement
      home-dwellers with more limited mobility. A tether-release paradigm was used to
      simulate a trip-type perturbation in 15 seniors across five flooring surfaces
      (three novel safety floors and one carpet compared to institutional-grade
      resilient rolled-sheeting). Kinetic and kinematic data tracked the displacement
      profiles of the underfoot centre-of-pressure and whole-body centre-of-mass, which
      were used to characterize compensatory balance reactions. Difference tests
      (ANOVA) found that the onset of the compensatory balance reaction was not
      associated with floor condition, nor were the timing and magnitude of peak centre
      of-pressure excursion (minimum margin of safety) and velocity. Accordingly, the
      minimum margin of safety of the centre-of-mass was not significantly different
      across floors. Equivalence tests supported these findings. This study provides
      evidence that the carpet and novel safety floors tested do not negatively
      influence characteristics of initial dynamic balance responses following a lean
      and-release perturbation compared to an institutional-grade resilient rolled
      sheeting surface. In combination with reports of substantial force attenuative
      properties during fall-related impacts, these findings support the promise of
      novel safety floors as a biomechanically effective strategy for reducing fall
      related injuries. 

PMID- 24726190
TI  - Temporal and spatial gait parameters in patients dependent on walking assistance
      after stroke: reliability and agreement between simple and advanced methods of
      assessment.
AB  - The aim of this study was to investigate the reliability of temporal and spatial
      gait parameters in patients dependent on walking assistance after severe stroke,
      and to examine agreement between simple and advanced methods. Twenty-one
      patients, admitted for in-patient multidisciplinary rehabilitation, were assessed
      repeatedly for walking function, both in a test corridor and a gait laboratory
      (3D camera system) before and after 11 weeks of rehabilitation. The test-retest
      reliability was examined using intraclass correlation (ICC1.1), and measurement
      error was reported by within-subject standard deviation (Sw). The agreement
      between different methods for assessing walking speed, cadence and step length
      was explored by Bland-Altman plots. High to excellent test-retest reliability was
      found between trials, both when assessed in the corridor (ICC: 0.93-0.99) and in
      the laboratory (ICC: 0.88-0.99). Agreement between methods was satisfactory at
      baseline and was higher after the rehabilitation period. Agreement was found to
      be slightly better at lower walking speeds and for shorter step lengths. The
      results implicate that temporal-spatial gait parameters may be measured reliably
      by both simple and advanced methods in dependent walkers after stroke. A high
      level of agreement was found between the two methods for walking speed, cadence
      and average step length at both test points. 

PMID- 24726191
TI  - Vector field statistics for objective center-of-pressure trajectory analysis
      during gait, with evidence of scalar sensitivity to small coordinate system
      rotations.
AB  - Center of pressure (COP) trajectories summarize the complex mechanical
      interaction between the foot and a contacted surface. Each trajectory itself is
      also complex, comprising hundreds of instantaneous vectors over the duration of
      stance phase. To simplify statistical analysis often a small number of scalars
      are extracted from each COP trajectory. The purpose of this paper was to
      demonstrate how a more objective approach to COP analysis can avoid particular
      sensitivities of scalar extraction analysis. A previously published dataset
      describing the effects of walking speed on plantar pressure (PP) distributions
      was re-analyzed. After spatially and temporally normalizing the data, speed
      effects were assessed using a vector-field paired Hotelling's T2 test. Results
      showed that, as walking speed increased, the COP moved increasingly posterior at
      heel contact, and increasingly laterally and anteriorly between ~60 and 85%
      stance, in agreement with previous independent studies. Nevertheless, two
      extracted scalars disagreed with these results. Furthermore, sensitivity analysis
      found that a relatively small coordinate system rotation of 5.5 degrees  reversed
      the mediolateral null hypothesis rejection decision. Considering that the foot
      may adopt arbitrary postures in the horizontal plane, these sensitivity results
      suggest that non-negligible uncertainty may exist in mediolateral COP effects. As
      compared with COP scalar extraction, two key advantages of the vector-field
      approach are: (i) coordinate system independence, (ii) continuous statistical
      data reflecting the temporal extents of COP trajectory changes.

PMID- 24726193
TI  - Diagnosing organizing pneumonia: Limitations of radiology and pathology.

PMID- 24726192
TI  - Hydrogen sulfide maintains mesenchymal stem cell function and bone homeostasis
      via regulation of Ca(2+) channel sulfhydration.
AB  - Gaseous signaling molecules such as hydrogen sulfide (H2S) are produced
      endogenously and mediate effects through diverse mechanisms. H2S is one such
      gasotransmitters that regulates multiple signaling pathways in mammalian cells,
      and abnormal H2S metabolism has been linked to defects in bone homeostasis. Here,
      we demonstrate that bone marrow mesenchymal stem cells (BMMSCs) produce H2S in
      order to regulate their self-renewal and osteogenic differentiation, and H2S
      deficiency results in defects in BMMSC differentiation. H2S deficiency causes
      aberrant intracellular Ca(2+) influx because of reduced sulfhydration of cysteine
      residues on multiple Ca(2+) TRP channels. This decreased Ca(2+) flux
      downregulates PKC/Erk-mediated Wnt/beta-catenin signaling which controls
      osteogenic differentiation of BMMSCs. Consistently, H2S-deficient mice display an
      osteoporotic phenotype that can be rescued by small molecules that release H2S.
      These results demonstrate that H2S regulates BMMSCs and that restoring H2S levels
      via nontoxic donors may provide treatments for diseases such as osteoporosis that
      can arise from H2S deficiencies. 

PMID- 24726194
TI  - Effects of phthalates on the development and expression of allergic disease and
      asthma.
AB  - OBJECTIVE: To review recent evidence relating phthalate exposures to allergies
      and asthma and to provide an overview for clinicians interested in the relevance
      of environmental health research to allergy and who may encounter patients with
      concerns about phthalates from media reports. DATA SOURCES: PubMed, TOXLINE, and
      Web of Science were searched using the term phthalate(s) combined with the
      keywords allergy, asthma, atopy, and inflammation. STUDY SELECTIONS: Articles
      were selected based on relevance to the goals of this review. Studies that
      involved humans were prioritized, including routes and levels of exposure,
      developmental and early-life exposures, immunotoxicity, and the development of
      allergic disease. RESULTS: The general public and those with allergy are exposed
      to significant levels of phthalates via diet, pharmaceuticals, phthalate
      containing products, and ambient indoor environment via air and dust. Intravenous
      exposures occur through medical equipment. Phthalates are metabolized and
      excreted quickly in the body with metabolites measured in urine. Phthalates,
      which are known endocrine disrupting compounds, have been associated with
      oxidative stress and alterations in cytokine expression. Metabolites in human
      urine, particularly of the higher-molecular-weight phthalates, have been
      associated with allergies and asthma in multiple studies. CONCLUSION: Despite
      mounting evidence implicating phthalates, causation of allergic disease by these
      compounds cannot currently be established. In utero and early-life exposures and
      possible transgenerational effects are not well understood. However, considering
      the current evidence, reducing exposures to phthalates by avoiding processed and
      foods packaged and stored in plastics, personal care products with phthalates,
      polyvinyl chloride materials indoors, and reducing home dust is advised. Further
      longitudinal, molecular, and intervention studies are needed to understand the
      association between phthalates and allergic disease.

PMID- 24726195
TI  - Stress and anxiety effects on positive skin test responses in young adults with
      allergic rhinitis.
AB  - BACKGROUND: Anxiety and psychological stress affect allergy-related immune
      function. How these relations influence the evaluations of patients with allergic
      rhinitis is unknown. OBJECTIVE: To examine whether anxiety and stress exposure
      affect skin prick test (SPT) responses to common allergens for which patients
      with atopy showed no prior positive SPT response. METHODS: Patients with allergic
      rhinitis, evidenced by clinical history and SPT results, were admitted twice to a
      hospital research unit for 4 hours. In a crossover design, SPT wheals were
      assessed before and after the Trier Social Stress Test and then the following
      morning; for comparison, SPT wheals were assessed before and after a laboratory
      session without a stressor. Analyses focused on wheal responses for common
      allergens that tested negative (wheal size <3 mm larger than saline) from SPTs
      performed at multiple baseline assessments. RESULTS: After the Trier Social
      Stress Test, more anxious patients with atopy had a higher incidence of positive
      SPT reactions to antigens that previously tested negative. Anxiety was unrelated
      to positive SPT incidence under nonstressful conditions. Based on clinical
      symptom reports, newly positive SPT reactions after the stressor were apparently
      corrections of previously false-negative SPT reactions. The SPT wheal responses
      for allergens previously testing negative were enhanced after a stressor.
      Histamine (positive control) or saline (negative control) SPT responses were not
      affected. CONCLUSION: A laboratory stressor affected allergen SPT responses in
      more anxious patients with allergic rhinitis. In addition to clinical history,
      assessment of anxiety and current stress at the time of the SPT may provide
      valuable information about a patient's allergic status and aid in clinical
      decision making.

PMID- 24726196
TI  - Increased epidermal filaggrin in chronic idiopathic urticaria is associated with
      severity of urticaria.
AB  - BACKGROUND: Chronic idiopathic urticaria (CIU) and atopic dermatitis (AD) are
      common allergic skin diseases associated with severe pruritus. AD skin is
      characterized by filaggrin deficiency, but it has not been studied in CIU.
      OBJECTIVE: To compare the expression of filaggrin in skin from patients with CIU,
      patients with AD, and normal controls and to investigate whether altered
      filaggrin expression is associated with CIU severity. METHODS: Skin biopsies were
      obtained from 16 patients with CIU, 11 patients with AD, and 14 normal controls.
      Filaggrin expression was evaluated using real-time reverse transcriptase
      polymerase chain reaction and immunostaining. Urticaria activity score,
      transepidermal water loss, and skin pH were measured. RESULTS: FLG gene
      expression was significantly greater in lesional CIU skin compared with lesional
      AD skin (P < .01). The staining intensity of filaggrin was significantly
      increased in lesional CIU skin compared with skin from normal controls (P < .01)
      and lesional AD skin (P < .001). A significant correlation was observed between
      filaggrin staining intensity and urticaria activity score in patients with CIU (r
      = 0.538, P < .05). Transepidermal water loss was significantly increased in
      lesional skin of patients with AD compared with skin from normal controls (P <
      .01) and lesional skin from patients with CIU (P < .01). Skin pH was
      significantly decreased in lesional skin from patients with CIU compared with
      skin from normal controls (P < .01) and patients with AD (P < .001). CONCLUSION:
      Filaggrin is overexpressed in lesional CIU skin, and increased filaggrin
      expression is positively correlated with urticaria severity in CIU. Altered
      filaggrin expression has physiologic effects on transepidermal water loss and pH
      in the skin of patients with CIU, suggesting increased barrier function compared
      with skin from patients with AD.

PMID- 24726197
TI  - Relationship between urine dichlorophenol levels and asthma morbidity.
AB  - BACKGROUND: Chlorinated phenols are associated with atopic conditions, but it is
      not known whether they are associated with wheeze or asthma and whether atopy is
      involved in these associations. OBJECTIVES: To test the association between urine
      levels of 2 dichlorophenols (2,4- and 2,5-dichlorophenols) and asthma morbidity
      in atopic and nonatopic wheezers and between total serum immunoglobulin E (IgE)
      levels. METHODS: Data from a sample of 2,125 participants at least 6 years old
      from the US National Health and Nutrition Examination Survey 2005 to 2006 were
      analyzed. Asthma morbidity data were available for those participants who
      reported wheezing in the past year ("wheezers"; n = 250). This subsample was
      categorized as atopic or nonatopic. RESULTS: Atopic wheezers with higher 2,5
      dichlorophenol levels were more frequently diagnosed with asthma by a physician
      (odds ratio [OR] 4.7 for highest vs lowest tertile, P < .001), required more
      prescriptions for asthma medications (OR 2.2, P = .046), and reported more
      exercise-induced wheezing (OR 5.8, P = .045) than atopic wheezers with low
      dichlorophenol levels. Atopic wheezers with higher 2,5- or 2,4-dichloropheonol
      levels also were more likely to miss work or school because of wheezing (OR 10.0,
      P < .001; OR 11.4, P < .01, respectively). In contrast, in nonatopic wheezers,
      there were no significant associations between dichlorophenol levels and asthma
      morbidity measurements. The 2 dichlorophenol metabolites were positively
      associated with increased serum IgE levels in the larger study sample.
      CONCLUSION: These findings indicate that in patients with atopy and a history of
      wheezing, asthma morbidity is associated with high urinary dichlorophenol levels.
      Increased urine dichlorophenol levels are associated with higher total serum IgE.

PMID- 24726198
TI  - Yoga for asthma: a systematic review and meta-analysis.
AB  - BACKGROUND: Although yoga is frequently used by patients with asthma, its
      efficacy in alleviating asthma remains unclear. OBJECTIVE: To systematically
      assess and meta-analyze the available data on efficacy and safety of yoga in
      alleviating asthma. METHODS: MEDLINE/PubMed, Scopus, the Cochrane Central
      Register of Controlled Trials, PsycINFO, CAM-Quest, CAMbase, and IndMED were
      searched through January 2014. Randomized controlled trials of yoga for patients
      with asthma were included if they assessed asthma control, symptoms, quality of
      life, and/or pulmonary function. For each outcome, standardized mean differences
      (SMDs) or risk ratios (RRs) and 95% confidence intervals (CIs) were calculated.
      Risk of bias was assessed using the Cochrane tool. RESULTS: Fourteen randomized
      controlled trials with 824 patients were included. Evidence for effects of yoga
      compared with usual care was found for asthma control (RR, 10.64; 95% CI, 1.98 to
      57.19; P = .006), asthma symptoms (SMD, -0.37; 95% CI, -0.55 to -0.19; P < .001),
      quality of life (SMD, 0.86; 95% CI, 0.39 to 1.33; P < .001), peak expiratory flow
      rate (SMD, 0.49; 95% CI, 0.32 to 0.67; P < .001), and ratio of forced expiratory
      volume in 1 second to forced vital capacity (SMD, 0.50; 95% CI, 0.24 to 0.75; P <
      .001); evidence for effects of yoga compared with psychological interventions was
      found for quality of life (SMD, 0.61; 95% CI, 0.22 to 0.99; P = .002) and peak
      expiratory flow rate (SMD, 2.87; 95% CI, 0.14 to 5.60; P = .04). No evidence for
      effects of yoga compared with sham yoga or breathing exercises was revealed. No
      effect was robust against all potential sources of bias. Yoga was not associated
      with serious adverse events. CONCLUSION: Yoga cannot be considered a routine
      intervention for asthmatic patients at this point. It can be considered an
      ancillary intervention or an alternative to breathing exercises for asthma
      patients interested in complementary interventions.

PMID- 24726199
TI  - Prevalence of lower urinary tract symptoms in individuals with Down syndrome.
AB  - OBJECTIVES: Down syndrome (DS), which is caused by the trisomy of chromosome 21,
      is the most frequent of all genetic syndromes. The current study aims to estimate
      the prevalence of lower urinary tract symptoms (LUTS) in individuals with DS buy
      using the Dysfunctional Voiding Symptom Score (DVSS) and correlate with
      functional constipation, age, and gender, as well as determine the most sensitive
      and specific factors associated with LUTS. METHODS: LUTS was assessed in
      individuals with DS using a cross-sectional study through the application of a
      validated and adapted version of the DVSS for the Brazilian population. The
      presence of functional constipation was evaluated according to the Rome III
      criteria. RESULTS: Of the 114 individuals assessed, 84 were included in the study
      (median age 16 +/- 5.0 years, 66.7% female). The prevalence of LUTS was 27.3%.
      The symptoms were more frequent in males (OR 3.0, 95% CI 1.1-8.3, p = 0.03) and
      in individuals younger than 10 years of age (OR 5.2, 95% CI 1.8-14, p = 0.001).
      Functional constipation was observed in 50% of subjects. It was detected in
      95.65% of the individuals with LUTS and 32.78% without LUTS (OR 45.1, 95% CI 5.66
      301, p = 0.001). The symptom listed in question 8 ("push to pee") was the most
      specific indicator. When present, this symptom indicated a higher probability of
      LUTS (LR+ = 6.3), while the symptom listed in question 4 ("push for bowel
      movements to come out") showed high sensitivity and, when absent, indicated a
      lower probability of LUTS (LR- = 0.1). CONCLUSIONS: LUTS was more prevalent in
      young males with DS and appeared to improve with age. Functional constipation was
      strongly associated with LUTS. These findings will contribute to raising the
      awareness of professionals involved in the follow-up of individuals with DS
      regarding the clinical manifestations and the need for a standardized
      investigation of LUTS.

PMID- 24726200
TI  - Commentary to 'Practice changes in childhood surgery for ambiguous genitalia?'
      The slow road to change is driven by long-term outcomes.

PMID- 24726201
TI  - Health-related quality of life and treatment effects on children with functional
      incontinence, and their parents.
AB  - OBJECTIVE: To analyze treatment outcomes and the association between treatment
      effects and health-related quality of life (HRQoL) for incontinent children, and
      their parents. SUBJECTS AND METHODS: Health-related quality of life in 70
      consecutively treated children, and their parents, was assessed with the
      Pediatric Incontinence Questionnaire and the WHO-Quality-Of-Life-BREF
      questionnaire. This was assessed before and after three months of standardized
      treatment. RESULTS: In 44.3% of children, symptoms decreased by 50-89%. After
      three months of treatment, the HRQoL of children improved significantly. Children
      with bladder and bowel dysfunction had a significantly lower HRQoL than children
      with isolated nocturnal enuresis, daytime urinary incontinence or fecal
      incontinence. Parental HRQoL did not change significantly within three months of
      treatment. Parents showed a significantly lower mean in the 'psychological'
      domain of the WHO-QoL-BREF questionnaire compared to norms. CONCLUSION: Children
      with different subtypes of incontinence can be treated effectively within three
      months of therapy. After three months, significant improvements of HRQoL were
      shown. Parents showed no general reduction in their quality of life (QoL).
      Specific aspects of parental QoL were impaired, but did not improve during the
      treatment of their children.

PMID- 24726202
TI  - A new index to monitor central visual field progression in glaucoma.
AB  - PURPOSE: The visual field index (VFI) summarizes global visual field (VF) data
      and was developed to monitor glaucoma progression using 24-2 and 30-2 strategies.
      We applied similar principles and statistical procedures to develop a new
      parameter, the central field index (CFI), to monitor 10-2 VF progression. DESIGN:
      Retrospective cohort. PARTICIPANTS: Glaucoma patients with paracentral defects
      seen on 24-2 perimetry and followed up with at least 5 10-2 VF tests. METHODS:
      The CFI was developed by calculating age-corrected defect depth at test points
      obtained during 10-2 examinations. The sensitivities at these points were scored
      as percentages similar to the method described for the VFI: 100-[(|total
      deviation|/age-corrected normal threshold) * 100]. A weighting procedure was
      applied based on published estimates of the occipital cortical spatial
      magnification. For validation, we performed mixed linear model testing for the
      association between CFI rates of change (%/year) and known risk factors for
      glaucoma progression in a population with established glaucoma and at least 5 10
      2 VF tests. To determine whether the CFI was affected by cataract, as is known to
      occur with mean deviation (MD), we conducted a pilot evaluation comparing rates
      of CFI change in 3 groups: (1) eyes with cataract, (2) pseudophakic eyes, and (3)
      eyes in which cataract surgery was performed in the middle of the series. MAIN
      OUTCOME MEASURES: Rates of CFI and MD change. RESULTS: Central field index values
      were calculated for 176 eyes of 142 patients. The mean rate of CFI change of the
      entire sample was -1.10%/year (95% confidence interval, -1.03 to -1.16%/year).
      Elevated intraocular pressure (P<0.001) was associated significantly with faster
      CFI change, whereas lens status did not influence CFI rates of change (P>0.100)
      CONCLUSIONS: We developed and validated a new index to monitor central field
      progression that is minimally affected by the presence or removal of cataract and
      that correlates significantly with an important risk factor for glaucoma
      progression. This new index may become useful for glaucoma management, especially
      when combined with conventional static perimetry strategies.

PMID- 24726203
TI  - Acoustic performance of mesh compression paddles for a multimodality breast
      imaging system.
AB  - A system incorporating automated 3-D ultrasound and digital X-ray tomosynthesis
      is being developed for improved breast lesion detection and characterization. The
      goal of this work is to develop and test candidates for a dual-modality mesh
      compression paddle. A Computerized Imaging Reference Systems (Norfork, VA, USA)
      ultrasound phantom with tilted low-contrast cylindrical objects was used.
      Polyester mesh fabrics (1- and 2-mm spacing), a high-density polyethylene
      filament grid (Dyneema, DSM Dyneema, Stanley, NC, USA) and a solid
      polymethylpentene (TPX; Mitsui Plastics, Inc., White Plains, NY) paddle were
      compared with no overlying structures using a GE Logic 9 with M12L transducer. A
      viscous gel provided coupling. The phantom was scanned 10 times over 9 cm for
      each configuration. Image volumes were analyzed for signal strength, contrast and
      contrast-to-noise ratio. X-ray tests confirmed X-ray transparency for all
      materials. By all measures, both mesh fabrics outperformed TPX and Dyneema, and
      there were essentially no differences between 2-mm mesh and unobstructed
      configurations.

PMID- 24726204
TI  - Impact of a clinical pharmacist-led guidance team on cancer pain therapy in
      China: a prospective multicenter cohort study.
AB  - CONTEXT: Cancer treatment capacity in China is severely limited relative to the
      enormous size of the population; and many aspects of treatment, such as opioid
      protocols for pain control, are not standardized. To improve the quality of drug
      treatment, clinical pharmacists are taking a more active role in patient care.
      OBJECTIVES: This study compared the effectiveness of opioid treatment between
      cancer patients receiving interventions from Clinical Pharmacist-Led Guidance
      Teams (CPGTs) and a comparable control group. METHODS: This was a prospective,
      multicenter, double-arm, controlled study conducted in China. Multidisciplinary
      guidance teams were established and led by clinical pharmacists with expertise in
      cancer pain therapy. The CPGTs provided pre-therapy consultation and drug
      education to physicians, monitored prescriptions during treatment, and conducted
      patient follow-up. The process and outcome parameters of therapy were collected
      and analyzed with overall statistics and logistic regression. RESULTS: A total of
      542 patients were enrolled, 269 in the CPGT intervention group (CPGT group) and
      273 controls. Standardization of opioid administration was improved significantly
      in the CPGT group, including more frequent pain evaluation (P<0.001), more
      standardized dosing titration (P<0.001), and less frequent meperidine
      prescriptions (P<0.001). The pain scores in the CPGT group were significantly
      improved compared with the control group (P<0.05). The incidences of
      gastrointestinal adverse events were significantly lower in the CPGT group
      (constipation: P=0.041; nausea: P=0.028; vomiting: P=0.035), and overall quality
      of life was improved (P=0.032). No opioid addiction was encountered in the CPGT
      group. Risk analysis revealed that patient follow-up by pharmacists and the
      controlled dosing of opioids were the major factors in improving treatment
      efficacy. CONCLUSION: The CPGTs significantly improved standardization,
      efficiency, and efficacy of cancer pain therapy in China. In a country where
      clinical pharmacy is still developing, this is a valuable service model that may
      enhance cancer treatment capacity and efficacy while promoting recognition of the
      clinical pharmacy profession.

PMID- 24726206
TI  - Editorial for special issue on nasopharynx cancer.

PMID- 24726207
TI  - HPV and head and neck cancers: state-of-the-science.

PMID- 24726208
TI  - Severe sinus node dysfunction in a patient with juvenile neuronal ceroid
      lipofuscinosis.

PMID- 24726209
TI  - Novel MYH7 mutation associated with mild myopathy but life-threatening
      ventricular arrhythmias and noncompaction.

PMID- 24726210
TI  - Incident hyperkalemia may be an independent therapeutic target in low ejection
      fraction heart failure patients: insights from the HEAAL study.
AB  - BACKGROUND: Angiotensin receptor antagonists (ARBs) improve outcomes in patients
      with heart failure (HF) with reduced left ventricular ejection fraction, but may
      induce hyperkalemia (HK) and/or a worsening of renal function (WRF). METHODS AND
      RESULTS: The incidence and risk factors of HK and its inter-relationship with
      WRF, as well as associations with clinical outcome (death or admission for HF
      i.e. the primary outcome) in 3846 HF patients enrolled in the double blind HEAAL
      trial (losartan 150 mg/d vs. 50 mg/d) were assessed. Worsening of renal function
      was defined as a decrease in eGFR >20% from baseline and HK as serum K >5.5 or >5
      mmol/L. Higher dose of losartan increased serum potassium. Episodes of HK >5
      mmol/L or WRF occurred at least once in about half of the patients. WRF was
      associated with higher occurrence of HK (HR 1.19 (1.06-1.34)) and vice versa (HR
      1.35 (1.19-1.53)), but preceded HK in only about half of the events. High dose
      losartan improved outcome despite more frequent WRF and HK, both being
      independently associated with adverse outcomes in multivariate analyses.
      CONCLUSIONS: HK and WRF are common in HF patients. Both can be predicted from
      baseline risk factors and are therefore potentially preventable. Although
      associated with worse outcome, occurrence of any does not hinder the efficacy of
      high dose losartan. HK was associated with WRF and worse outcomes. Whether
      therapy targeting specifically HK may maximize the survival benefit derived from
      renin angiotensin aldosterone inhibitor use should be appropriately tested in
      future trials.

PMID- 24726211
TI  - Association of contrast-induced acute kidney injury with long-term cardiovascular
      events in acute coronary syndrome patients with chronic kidney disease undergoing
      emergent percutaneous coronary intervention.
AB  - BACKGROUND: The association between contrast-induced acute kidney injury (CI-AKI)
      and chronic kidney disease (CKD) in patients with acute coronary syndrome (ACS)
      treated with percutaneous coronary intervention (PCI) has not been fully
      reported. We evaluated the association of CI-AKI on cardiovascular events in ACS
      patients with CKD. METHODS: A total of 1059 ACS patients who underwent emergent
      PCI in our multicenter registry were enrolled (69+/-12 years, 804 men, 604 STEMI
      patients). CKD was defined as at least stage 3 CKD, and CI-AKI was defined as an
      increase of at least 0.5 mg/dL and/or an increase of at least 25% of pre-PCI to
      post-PCI serum creatinine levels within 1 week after the procedure. Primary
      endpoints included cardiovascular death, myocardial infarction, and
      cerebrovascular disorder (stroke or transient ischemic attack). RESULTS: In our
      study, 368 (34.7%) patients had CKD. During follow-up periods (435+/-330 days),
      CI-AKI and primary endpoints occurred in 164 (15.5%) patients and 106 (10.0%)
      patients, respectively. Multivariate Cox proportional hazards model revealed that
      age, female gender, peak creatinine kinase>4000, IABP use, CI-AKI (hazard ratio
      [HR], 2.17; 95% confidential interval [CI], 1.52 to 4.00; P<0.001), and CKD (HR,
      1.66; 95% CI, 1.01 to 2.72; P=0.046) were independent predictors of primary
      endpoints. Kaplan-Meier analysis showed that occurrence of primary endpoints
      increased significantly with an increase in CKD stage, and CI-AKI yielded worse
      long-term prognosis at every stage of CKD (P<0.001). CONCLUSIONS: CI-AKI was
      revealed to be a significant incremental predictor of cardiovascular events at
      each stage of CKD in ACS patients.

PMID- 24726212
TI  - Treatment plan comparison between stereotactic body radiation therapy techniques
      for prostate cancer: non-isocentric CyberKnife versus isocentric RapidArc.
AB  - PURPOSE: The aim of this study was to evaluate the feasibility and dose
      distribution of two different stereotactic body radiation therapy (SBRT)
      techniques, isocentric RapidArc (RA) and non-isocentric CyberKnife (CK), for the
      treatment of localized prostate cancer. METHODS: Two groups of patients (Groups 1
      and 2 with ten patients per group) treated with CK were re-planned with RA. The
      patients were grouped according to the rectum constraint used (Group1, maximum
      dose for rectum; Group 2, dose-volume histogram for rectum). The prescription
      dose was 37.5 Gy in five fractions. The two SBRT techniques were compared by
      target coverage, normal tissue sparing, and dose distribution parameters. Monitor
      units (MUs) and the delivery time were likewise compared to assess delivery
      efficiency. RESULTS: The RA plans consistently exhibited superior PTV coverage
      and better rectum sparing at low doses in the both groups. The conformity and
      heterogeneity indices of the RA plans were better than the CK plans.
      Additionally, the RA plans resulted in fewer low-dose regions, lower MUs, and
      faster delivery times than the CK plans. CONCLUSIONS: The good dosimetric
      distribution and shorter delivery time make RA an attractive SBRT technique for
      the treatment of localized prostate cancer.

PMID- 24726213
TI  - Ten common questions (and their answers) on medical futility.
AB  - The term medical futility is frequently used when discussing complex clinical
      scenarios and throughout the medical, legal, and ethics literature. However, we
      propose that health care professionals and others often use this term
      inaccurately and imprecisely, without fully appreciating the powerful, often
      visceral, response that the term can evoke. This article introduces and answers
      10 common questions regarding medical futility in an effort to define, clarify,
      and explore the implications of the term. We discuss multiple domains related to
      futility, including the biological, ethical, legal, societal, and financial
      considerations that have a bearing on definitions and actions. Finally, we
      encourage empathetic communication among clinicians, patients, and families and
      emphasize how dialogue that seeks an understanding of multiple points of view is
      critically important in preventing or attenuating conflict among the involved
      parties. 

PMID- 24726215
TI  - Uterine transplantation.

PMID- 24726214
TI  - Atypical embryo phenotypes identified by time-lapse microscopy: high prevalence
      and association with embryo development.
AB  - OBJECTIVE: To characterize atypical dynamic embryo phenotypes identified by time
      lapse microscopy, evaluate their prevalence, and determine their association with
      embryo development. DESIGN: Retrospective multicenter cohort study. SETTING: Five
      IVF clinics in the United States. PATIENT(S): Sixty-seven women undergoing IVF
      treatment with 651 embryos. INTERVENTION(S): Embryo videos were retrospectively
      analyzed for atypical phenotypes. MAIN OUTCOME MEASURE(S): Identification of four
      groups of atypical embryo phenotypes: abnormal syngamy (AS), abnormal first
      cytokinesis (A1(cyt)), abnormal cleavage (AC), and chaotic cleavage (CC).
      Prevalence and association with embryo morphology and development potential were
      evaluated. RESULT(S): A high prevalence of atypical phenotypes was observed among
      embryos: AS 25.1% (163/649), A1(cyt) 31.0% (195/639), AC 18% (115/639) and CC 15%
      (96/639). A high percentage of embryos with atypical phenotype(s) had good
      quality on day 3 (overall grade good or fair): AS 78.6% (70/89); A1(cyt) 79.7%
      (94/119), AC 86.4% (70/81), and CC 35.2% (19/54), but the blastocyst formation
      rates for these embryos were significantly lower compared with their respective
      control groups: AS 21.5% vs. 44.9%, A1(cyt) 21.7% vs. 44.6%, AC 11.7% vs. 43.1%,
      and CC 14.0% vs. 42.3%. CONCLUSION(S): Embryos exhibiting atypical phenotypes are
      highly prevalent in human embryos and show significantly lower developmental
      potential than control embryos. CLINICAL TRIAL REGISTRATION NUMBER: NCT01369446.

PMID- 24726216
TI  - Comparability of antimullerian hormone levels among commercially available
      immunoassays.
AB  - OBJECTIVE: To compare antimullerian hormone (AMH) levels among three commercially
      available AMH immunoassays: AMH Gen II (Beckman Coulter), Ultrasensitive AMH
      (Ansh Labs), and picoAMH (Ansh Labs). DESIGN: Cross-sectional. SETTING: Academic
      reproductive endocrinology program. PATIENT(S): 90 newly diagnosed breast cancer
      patients before cancer treatment. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S):
      Proportion of detectable AMH levels by immunoassay, and comparability among
      assays. RESULT(S): At a mean age of 38.1 years, the median (interquartile range)
      AMH level for the cohort was 0.92 [1.35] ng/mL for the Gen II assay, 1.68 [2.30]
      ng/mL for the Ultrasensitive assay, and 1.52 [2.41] ng/mL for the picoAMH assay.
      Significantly higher proportions of detectable AMH levels were observed with the
      picoAMH kit (97%) compared with both the Gen II (84%) and Ultrasensitive (92%)
      assays. Although the AMH results were highly correlated among the assays (r =
      0.92-0.99), the Gen II AMH levels were consistently lower than both
      Ultrasensitive and picoAMH levels. Moreover, as AMH levels increased, the
      magnitude of difference grew larger between Gen II and each of the other two
      assays. CONCLUSION(S): Measurement of AMH levels with the picoAMH kit maximized
      detection at very low levels, particularly in contrast with the Gen II kit.
      Conversion of AMH levels from different immunoassays using regression equations
      is potentially highly inaccurate.

PMID- 24726217
TI  - Reply of the authors.

PMID- 24726205
TI  - Heparin-induced thrombocytopenia in the critically ill: interpreting the 4Ts test
      in a randomized trial.
AB  - BACKGROUND: Thrombocytopenia occurs in 20% to 45% of critically ill medical
      surgical patients. The 4Ts heparin-induced thrombocytopenia (HIT) score (with 4
      domains: Thrombocytopenia, Timing of thrombocytopenia, Thrombosis and oTher
      reason[s] for thrombocytopenia) might reliably identify patients at low risk for
      HIT. Interobserver agreement on 4Ts scoring is uncertain in this setting.
      OBJECTIVE: To evaluate whether a published clinical prediction rule (the "4Ts
      score") reliably rules out HIT in "low-risk" intensive care unit (ICU) patients
      as assessed by research coordinators (who prospectively scored) and 2
      adjudicators (who scored retrospectively) during an international heparin
      thromboprophylaxis trial (PROTECT, NCT00182143). METHODS: Of 3746 medical
      surgical ICU patients in PROTECT, 794 met the enrollment criteria for this HIT
      substudy. Enrollment was predicated on one of the following occurring in ICU:
      platelets less than 50*10(9)/L, platelets decreased to 50% of ICU admission value
      (if admission value<100*10(9)/L), any venous thrombosis, or if HIT was otherwise
      clinically suspected. Independently, 4Ts scores were completed in real time by
      research coordinators blinded to study drug and laboratory HIT results, and
      retrospectively by 2 adjudicators blinded to study drug, laboratory HIT results,
      and research coordinators' scores; the adjudicators arrived at consensus in all
      cases. Of the 763 patients, 474 had a central or local laboratory HIT test
      performed and had 4Ts scoring by adjudicators; 432 were scored by trained
      research coordinators. Heparin-induced thrombocytopenia was defined by a
      centrally performed positive serotonin release assay (SRA). RESULTS: Of the 474
      patients with central adjudication, 407 (85.9%) had a 4Ts score of 3 or lower,
      conferring a low pretest probability (PTP) of HIT; of these, 6 (1.5% [95%
      confidence interval, 0.7%-3.2%) had a positive SRA. Fifty-nine (12.4%) had a
      moderate PTP (4Ts score of 4-5); of these, 4 (6.8%) had a positive SRA. Eight
      patients had a high PTP (4Ts score of >=6); of these, 1 (12.5%) had a positive
      SRA. Raw agreement between research coordinators and central adjudication on each
      domain of the 4Ts score and low, intermediate, and high PTP was good. However,
      chance-corrected agreement was variable between adjudicators (weighted kappa
      values of 0.31-0.93) and between the adjudicator consensus and research
      coordinators (weighted kappa values of 0.13 and 0.78). Post hoc review of the 6
      SRA-positive cases with an adjudicated low PTP demonstrated that their scores
      would have been increased if the adjudicators had had additional information on
      heparin exposure prior to ICU admission. In general, the fourth domain of 4Ts
      (oTher causes of thrombocytopenia) generated the most disagreement. CONCLUSIONS:
      Real-time 4Ts scoring by research coordinators at the time of testing for HIT was
      not consistent with 4Ts scores obtained by central adjudicators. The results of
      this comprehensive HIT testing highlight the need for further research to improve
      the assessment of PTP scoring of HIT for critically ill patients.

PMID- 24726218
TI  - Acute epididymitis induces alterations in sperm protein composition.
AB  - OBJECTIVE: To use a proteomic approach to evaluate possible postinflammatory
      alterations in the protein composition of motile sperm in patients 3 months after
      acute epididymitis. DESIGN: Prospective case-control study. SETTING: University
      medical school research laboratory. PATIENT(S): Eight patients 3 months after
      acute unilateral epididymitis and 10 healthy controls. INTERVENTION(S): None.
      MAIN OUTCOME MEASURE(S): Proteome analysis of sperm samples collected by swim-up
      from control and acute epididymitis patients analyzed by two-dimensional gel
      electrophoresis and subsequent protein identification by matrix-assisted laser
      desorption/ionization-time-of-flight (MALDI-TOF) mass spectrometry;
      immunofluorescence staining for mitochondrial ATP synthase subunit beta (ATP5B),
      alpha-tubulin (TUBA1A), and tubulin-beta2c (TUBB4B) for validation purposes.
      RESULT(S): Proteome analysis identified 35 proteins in sperm from epididymitis
      patients that were down-regulated, irrespective of subcellular localization and
      biologic function. Furthermore, immunofluorescence microscopy confirmed ATP5B,
      TUBA1A, and TUBB4B were less abundantly expressed in epididymitis samples
      compared with controls. CONCLUSION(S): Despite normal semen parameters observed
      by conventional semen analysis in patients after epididymitis, significant
      changes to sperm protein composition were observed. These changes may be
      implicated as additional factors contributing to subfertility/infertility in men
      after episodes of epididymitis.

PMID- 24726219
TI  - Toward adhesion-free endoscopy?

PMID- 24726220
TI  - Does the age of the recipient influence the probability of pregnancy among
      recipients of oocyte donation?

PMID- 24726221
TI  - Relationship between testosterone and sexual function in infertile men.

PMID- 24726222
TI  - X-chromosome inactivation in female newborns conceived by assisted reproductive
      technologies.
AB  - OBJECTIVE: To investigate X-chromosome inactivation (XCI) skewing in female
      newborns conceived by intracytoplasmic sperm injection (ICSI), in vitro
      fertilization (IVF), and naturally. DESIGN: Case-control study. SETTING: Research
      institution. PATIENT(S): A total of 185 female newborns, including 60 conceived
      by intracytoplasmic sperm injection (ICSI), 73 by in vitro fertilization (IVF),
      and 52 naturally conceived (NC). INTERVENTION(S): DNA was extracted from
      umbilical cord blood after birth. MAIN OUTCOME MEASURE(S): XCI skewing values
      determined by assaying allelic ratio of methylated alleles at the androgen
      receptor (AR), fragile X mental retardation 1 (FMR1), and DXS6673E loci.
      RESULT(S): In the comparison of the ICSI, IVF, and NC populations, the frequency
      of skewing >= 75% (7.0% vs. 5.7% vs. 2.0%, respectively) or >= 90% (0 vs. 1.4%
      vs. 2.0%, respectively) was not statistically significantly different. The mean
      level of skewing between the ICSI, IVF, and NC groups also did not differ (63.7%
      vs. 61.8% vs. 60.7%, respectively). Skewing variability was observed in the
      placentas of the two extremely skewed cases. The parental origin of the
      preferentially inactivated X chromosome in the extremely skewed IVF and NC cases
      were maternal and paternal, respectively. CONCLUSION(S): The assisted
      reproductive technologies of ICSI and IVF do not appear to affect XCI skewing.
      Skewing variability within the placentas analyzed supports the theory that weaker
      selective pressures occur in the placenta that could result in skewed
      inactivation. Our study is the largest to date to investigate this epigenetic
      phenomenon in infants conceived by ICSI and IVF alongside age-matched NC
      controls.

PMID- 24726223
TI  - Electroejaculation in psychogenic anejaculation.
AB  - OBJECTIVE: To evaluate the results of treatment with electroejaculation (EEJ),
      intrauterine insemination (IUI), and IVF/intracytoplasmic sperm injection
      (IVF/ICSI) in patients with psychogenic anejaculation (PAE). DESIGN:
      Retrospective clinical study. SETTING: Academic tertiary referral fertility
      center. PATIENT(S): Eleven male patients diagnosed with psychogenic anejaculation
      (PAE) were included. Median age at the time of first treatment with EEJ was 33.0
      (interquartile range, 29.0-36.0) years. INTERVENTION(S): Electroejaculation, IUI,
      and IVF/ICSI. MAIN OUTCOME MEASURE(S): Semen analysis, fertilization rate,
      implantation rate, pregnancy rate, and delivery rate. RESULT(S): A total of 60
      EEJs were performed in 11 patients. Mean VCM (volume [mL] * concentration [sperm
      cells/mL] * percentage progressive motile cells) of the retrieved sperm of all
      EEJs was 17.5 * 10(6) (SD 16.5 * 10(6)). Yielded semen was used in a total of 26
      ICSI procedures in seven couples. The fertilization rate was 65.6% (80 of 122).
      The ICSI cycles resulted in five pregnancies; of these, one resulted in a
      spontaneous abortion in the first trimester. Three couples were treated with 34
      IUI cycles, which resulted in live births in four pregnancies. CONCLUSION(S):
      Electroejaculation is a suitable and effective treatment that can be used in men
      with psychogenic anejaculation. The retrieved semen can be used successfully in
      assisted reproductive technology treatment. In this study EEJ resulted in
      pregnancies and the birth of eight healthy children.

PMID- 24726224
TI  - Cold loop hysteroscopic technique for submucous myomas.

PMID- 24726225
TI  - We need a prospective varicocelectomy trial.

PMID- 24726226
TI  - Pharmacokinetics of two low-dose levonorgestrel-releasing intrauterine systems
      and effects on ovulation rate and cervical function: pooled analyses of phase II
      and III studies.
AB  - OBJECTIVE: To assess the pharmacokinetics and pharmacodynamics of levonorgestrel
      intrauterine system (LNG-IUS) 13.5 mg and LNG-IUS 19.5 mg (total content).
      DESIGN: Pooled pharmacokinetic and pharmacodynamic analyses of phase II and III
      studies. SETTING: Randomized, open-label, multicenter studies. PATIENT(S):
      Nulliparous and parous women. INTERVENTION(S): Levonorgestrel intrauterine system
      13.5 mg, LNG-IUS 19.5 mg, or LNG-IUS 20 MUg/24 h (total content 52 mg). MAIN
      OUTCOME MEASURE(S): Pharmacokinetics of LNG, ovulation rate, cervical function,
      and endometrium effects. RESULT(S): The in vivo LNG release rate of LNG-IUS 13.5
      mg was approximately 14 MUg/24 h after 24 days, declining progressively to 5
      MUg/24 h after 3 years. The average LNG serum concentration over 3 years of use
      was 74.3 ng/L, 114 ng/L, and 218 ng/L for LNG-IUS 13.5 mg, LNG-IUS 19.5 mg, and
      LNG-IUS 20 MUg/24 h, respectively. All treatments showed very similar
      progestogenic effects on cervical mucus, with low and similar cervical scores
      throughout treatment. Ovulation was observed in the majority of women in all
      groups where assessment was possible, although there was a lower incidence of
      anovulation with LNG-IUS 13.5 mg and LNG-IUS 19.5 mg compared with LNG-IUS 20
      MUg/24 h. The progestogenic effect on the endometrium was marked in all three LNG
      IUS groups. CONCLUSION(S): Levonorgestrel intrauterine system 13.5 mg and LNG-IUS
      19.5 mg result in alower systemic exposure to LNG, lower incidence of
      anovulation, and similar progestin impact on the endometrium and cervical
      function compared with LNG-IUS 20 MUg/24 h.

PMID- 24726227
TI  - Reply of the authors.

PMID- 24726229
TI  - Delayed appearance of wing-beating tremor after liver transplantation in a
      patient with Wilson disease.
AB  - Orthotopic liver transplantation (OLT) is the sole etiological treatment for
      Wilson disease (WD), but several neurological complications after OLT have been
      reported. We report a WD patient who developed a unilateral wing-beating tremor
      6years after OLT. New neurological symptoms develop immediately after OLT in most
      cases. In our patient, the onset of extrapyramidal symptoms was at a prolonged
      interval after OLT. To our knowledge this is the first patient with delayed
      extrapyramidal symptoms after OLT in WD where the pathophysiology of these late
      extrapyramidal symptoms is still unknown. 

PMID- 24726228
TI  - Old stones' song: use-wear experiments and analysis of the Oldowan quartz and
      quartzite assemblage from Kanjera South (Kenya).
AB  - Evidence of Oldowan tools by ~2.6 million years ago (Ma) may signal a major
      adaptive shift in hominin evolution. While tool-dependent butchery of large
      mammals was important by at least 2.0 Ma, the use of artifacts for tasks other
      than faunal processing has been difficult to diagnose. Here we report on use-wear
      analysis of ~2.0 Ma quartz and quartzite artifacts from Kanjera South, Kenya. A
      use-wear framework that links processing of specific materials and tool motions
      to their resultant use-wear patterns was developed. A blind test was then carried
      out to assess and improve the efficacy of this experimental use-wear framework,
      which was then applied to the analysis of 62 Oldowan artifacts from Kanjera
      South. Use-wear on a total of 23 artifact edges was attributed to the processing
      of specific materials. Use-wear on seven edges (30%) was attributed to animal
      tissue processing, corroborating zooarchaeological evidence for butchery at the
      site. Use-wear on 16 edges (70%) was attributed to the processing of plant
      tissues, including wood, grit-covered plant tissues that we interpret as
      underground storage organs (USOs), and stems of grass or sedges. These results
      expand our knowledge of the suite of behaviours carried out in the vicinity of
      Kanjera South to include the processing of materials that would be 'invisible'
      using standard archaeological methods. Wood cutting and scraping may represent
      the production and/or maintenance of wooden tools. Use-wear related to USO
      processing extends the archaeological evidence for hominin acquisition and
      consumption of this resource by over 1.5 Ma. Cutting of grasses, sedges or reeds
      may be related to a subsistence task (e.g., grass seed harvesting, cutting out
      papyrus culm for consumption) and/or a non-subsistence related task (e.g.,
      production of 'twine,' simple carrying devices, or bedding). These results
      highlight the adaptive significance of lithic technology for hominins at Kanjera.

PMID- 24726230
TI  - Primary intracranial haemangiopericytoma: comparison of survival outcomes and
      metastatic potential in WHO grade II and III variants.
AB  - Primary intracranial haemangiopericytomas (HPC) are rare, highly vascular tumours
      with a high propensity for local recurrence and distant metastasis. Optimal
      treatment includes maximal surgical resection followed by adjuvant radiotherapy.
      In 2007, new histopathological grading criteria were introduced to differentiate
      between high grade (World Health Organization [WHO] grade III) and low grade (WHO
      grade II) tumours. Given the rarity of this tumour, there is a paucity of
      information regarding the prognostic significance of histological grade. We
      conducted a retrospective review of our 20 year experience in treating 27
      patients with HPC at our institution. Statistical analysis to compare overall
      survival, local recurrence rate and metastatic potential between the two grades
      were conducted using Kaplan-Meier analysis. The estimated median survival for
      grade II HPC was 216 months and for grade III tumours was 142 months. On
      multivariate analysis, grade II tumours were associated with better survival than
      grade III lesions (hazard ratio=0.16, 95% confidence interval 0.26-0.95;
      p=0.044). During the study period, 33% of grade III tumours developed local
      recurrence compared to 21% of grade II tumours. Metastases were found in 36% of
      grade II patients and 25% of grade III patients. There was no significant
      statistical difference in local recurrence rate and metastasis between the two
      grades. Higher histological grading in HPC is associated with worse overall
      survival. However based on our series higher histological grading is not
      associated with higher local recurrence or distant metastatic rates.

PMID- 24726231
TI  - The best practice tariff and hip fractures: How can Northern Ireland keep up?
AB  - INTRODUCTION: Current hip fractures guidelines recommend surgery within 36 h of
      admission. The 2011 National Hip Fracture Database (NHFD) report shows our
      institute has the fewest patients meeting this target (9%). Northern Irelands'
      exclusion from the "Best Practice Tariff" means no incentive-led treatment or
      prioritisation of hip fracture patients. METHOD: We performed a systematic review
      of post-operative results to highlight deficiencies in delivery of patient care.
      We reviewed 702 patients admitted between September 2009 and April 2012. Patients
      were prospectively identified and added to our Fracture Outcome and Research
      Database (FORD). Results were compared to national average values from the NHFD.
      RESULTS: 16.7% of patients met the 36-h target to theatre compared to the UK
      average of 66%. 81.7% underwent a pre-operative orthogeriatric review. The main
      reasons for surgical delay were inadequate theatre space (58%) and medically
      unfit patients (29%). After exclusion of medically unfit patients, medically fit
      patients were divided into delayed surgery and not delayed categories. Medically
      fit patients who had delayed surgery had inferior outcomes- longer hospital stay
      and higher mortality as an inpatient and at 30 days. CONCLUSION: Without a change
      in funding, Northern Ireland will struggle to compete with the UK mainland and
      decrease mortality in this patient group.

PMID- 24726232
TI  - Dual catalytic role of the metal ion in nickel-assisted peptide bond hydrolysis.
AB  - In our previous research we demonstrated the sequence specific peptide bond
      hydrolysis of the R1-(Ser/Thr)-Xaa-His-Zaa-R2 in the presence of Ni(II) ions. The
      molecular mechanism of this reaction includes an N-O acyl shift of the R1 group
      from the Ser/Thr amine to the side chain hydroxyl group of this amino acid. The
      proposed role of the Ni(II) ion is to establish favorable geometry of the
      reacting groups. In this work we aimed to find out whether the crucial step of
      this reaction--the formation of the intermediate ester--is reversible. For this
      purpose we synthesized the test peptide Ac-QAASSHEQA-am, isolated and purified
      its intermediate ester under acidic conditions, and reacted it, alone, or in the
      presence of Ni(II) or Cu(II) ions at pH 8.2. We found that in the absence of
      either metal ion the ester was quickly and quantitatively (irreversibly)
      rearranged to the original peptide. Such reaction was prevented by either metal
      ion. Using Cu(II) ions as CD spectroscopic probe we showed that the metal binding
      structures of the ester and the final amine are practically identical. Molecular
      calculations of Ni(II) complexes indicated the presence of steric strain in the
      substrate, distorting the complex structure from planarity, and the absence of
      steric strain in the reaction products. These results demonstrated the dual
      catalytic role of the Ni(II) ion in this mechanism. Ni(II) facilitates the acyl
      shift by setting the peptide geometry, and prevents the reversal of the acyl
      shift, by stabilizing subsequent reaction products.

PMID- 24726233
TI  - Adverse events in post-acute care: the Office of the Inspector General's report.

PMID- 24726234
TI  - Monitoring of tumor response to Cisplatin using optical spectroscopy.
AB  - INTRODUCTION: Anatomic imaging alone is often inadequate for tuning systemic
      treatment for individual tumor response. Optically based techniques could
      potentially contribute to fast and objective response monitoring in personalized
      cancer therapy. In the present study, we evaluated the feasibility of dual
      modality diffuse reflectance spectroscopy-autofluorescence spectroscopy (DRS-AFS)
      to monitor the effects of systemic treatment in a mouse model for hereditary
      breast cancer. METHODS: Brca1(-/-); p53(-/-) mammary tumors were grown in 36
      mice, half of which were treated with a single dose of cisplatin. Changes in the
      tumor physiology and morphology were measured for a period of 1 week using dual
      modality DRS-AFS. Liver and muscle tissues were also measured to distinguish
      tumor-specific alterations from systemic changes. Model-based analyses were used
      to derive different optical parameters like the scattering and absorption
      coefficients, as well as sources of intrinsic fluorescence. Histopathologic
      analysis was performed for cross-validation with trends in optically based
      parameters. RESULTS: Treated tumors showed a significant decrease in Mie
      scattering slope and Mie-to-total scattering fraction and an increase in both fat
      volume fraction and tissue oxygenation after 2 days of follow-up. Additionally,
      significant tumor-specific changes in the fluorescence spectra were seen. These
      longitudinal trends were consistent with changes observed in the histopathologic
      analysis, such as vital tumor content and formation of fibrosis. CONCLUSIONS:
      This study demonstrates that dual-modality DRS-AFS provides quantitative
      functional information that corresponds well with the degree of pathologic
      response. DRS-AFS, in conjunction with other imaging modalities, could be used to
      optimize systemic cancer treatment on the basis of early individual tumor
      response.

PMID- 24726235
TI  - Percutaneous Fine-Needle 5% Ethanol-Cisplatin Intratumoral Injection Combined
      with Second-Line Chemotherapy Improves On the Standard of Care in Patients with
      Platinum-Pretreated Stage IV Non-Small Cell Lung Cancer.
AB  - BACKGROUND: Efficacy of second-line chemotherapy in platinum-pretreated non-small
      cell lung cancer (NSCLC) is poor. This study investigated efficacy of computed
      tomography-guided percutaneous fine-needle 5% ethanol-cisplatin intratumoral
      injection (CT-PFNECII) combined with second-line chemotherapy in patients with
      platinum-pretreated stage IV NSCLC. PATIENTS: Between October 2011 and July 2013,
      34 eligible patients were randomly assigned to receive either CT-PFNECII combined
      with second-line chemotherapy (combination group, n = 17) or second-line
      chemotherapy alone (chemotherapy group, n = 17). The primary end points were the
      proportions of patients who achieved an overall response rate (ORR) and disease
      control rate (DCR). Secondary end points were median survival and progression
      free survival (PFS). RESULTS: The ORR and DCR in the combination group were
      significantly higher than in the chemotherapy group (23.53% vs 11.76% for ORR, P
      < .01; and 58.82% vs 35.29% for DCR, P < .01). Compared with patients in the
      chemotherapy group, patients in the combination group had significantly longer
      PFS (5.4 months vs 3.0 months, P < .01) and median survival (9.5 months vs 5.3
      months, P < .01). CONCLUSIONS: CT-PFNECII combined with second-line chemotherapy
      provided a higher response rate and improved survival than second-line
      chemotherapy for patients with platinum-pretreated stage IV NSCLC.

PMID- 24726236
TI  - Reversible cerebellar ataxia due to ovarian teratoma.
AB  - Cerebellar dysfunction is a classic paraneoplastic syndrome associated with
      various types of cancer, including gynecological and breast tumors, small-cell
      lung cancer, thymoma, and Hodgkin's lymphoma. We present a 22-year-old woman with
      acute cerebellar ataxia that subsided upon removal of an ovarian teratoma. This
      patient may represent a new category of immune-mediated cerebellar ataxia that is
      reversible with removal of an underlying tumor. 

PMID- 24726237
TI  - Eyelid apraxia associated with deep brain stimulation of the periaqueductal gray
      area.
AB  - We report a patient with eyelid apraxia following deep brain stimulation of the
      periaqueductal gray area. Based on the position of our electrode, we argue that
      the phenomenon is linked to inhibition of the nearby central caudal nucleus of
      the oculomotor nucleus by high frequency stimulation. 

PMID- 24726239
TI  - Predictors for recurrence after urethroplasty in pediatric and adolescent
      stricture urethra.
AB  - OBJECTIVE: This study aims at evaluating factors predicting recurrence of
      urethral stricture following urethroplasty in pediatric patients at a tertiary
      care center. PATIENTS AND METHODS: Fifty-two patients of up to 18 years of age,
      who underwent urethroplasty, were reviewed. Duration of symptoms, etiology,
      previous intervention, and site of stricture, surgical modality, stricture
      length, and spongiofibrosis at stricture site, recurrence, and ancillary
      procedures required were recorded. RESULTS: Forty-two (82.76%) patients (Group I)
      had recurrence-free course on follow-up. Of the 10 patients with recurrence
      (Group II), 9 had PTS and 1 had IS (p = 0.04). Most of the factors evaluated did
      not differ statistically between the groups; however, length of stricture (1.8
      vs. 4.3 cm, p < 0.001) and degree of spongiofibrosis (61% vs. 90%, p = 0.003)
      were significantly different. Seven patients with recurrence were managed with
      single procedures, but three required multiple procedures because of multiple
      recurrences. History of incision and drainage for paraurethral abscess was
      significantly higher (28.6% vs. 100%, p = 0.002) in patients who had multiple
      recurrences. CONCLUSIONS: Etiology, fibrosis at local site, and stricture length
      have significant impact on recurrence of pediatric urethral stricture disease.
      Associated paraurethral abscess may further compromise the outcome of
      urethroplasty.

PMID- 24726240
TI  - Properties of Swedish posttraumatic stress measures after a disaster.
AB  - This study evaluated the properties of Swedish versions of self-report measures
      of posttraumatic stress disorder (PTSD), with emphasis on the Impact of Event
      Scale-Revised (IES-R). Survey data from adult survivors 1, 3, and 6 years after
      the 2004 Indian Ocean tsunami (n=1506) included the IES-R (from which the IES-6
      was derived) and the 12-item General Health Questionnaire (GHQ-12). The PTSD
      Checklist (PCL) was included in one survey. A structured clinical interview was
      performed after 6 years (n=142). Factor analyses of the IES-R and PCL indicated
      that a dysphoric-arousal model provided good fit invariant across assessments.
      Both measures were accurate in excluding PTSD while all measures provided poorer
      positive predictive values. The IES-R, but not the IES-6 and GHQ-12, evidenced
      stability across assessments. In conclusion, the Swedish IES-R and PCL are sound
      measures of chronic PTSD, and the findings illustrate important temporal aspects
      of PTSD assessment. 

PMID- 24726241
TI  - An examination of the incremental contribution of emotion regulation difficulties
      to health anxiety beyond specific emotion regulation strategies.
AB  - Given the potential transdiagnostic importance of emotion dysregulation, as well
      as a lack of research examining emotion dysregulation in relation to health
      anxiety, the present study sought to examine associations among specific emotion
      regulation strategies (cognitive reappraisal and expressive suppression), emotion
      regulation difficulties, and health anxiety in a physically healthy sample of
      adults (N=482). As hypothesized, results of a series of hierarchical multiple
      regression analyses showed that emotion regulation difficulties provided a
      significant incremental contribution, beyond the specific emotion regulation
      strategies, in predicting each of the three health anxiety variables. Among the
      six dimensions of emotion regulation difficulties, the dimension representing
      perceived access to effective emotion regulation strategies was the only emotion
      regulation difficulty dimension that predicted all three health anxiety variables
      beyond the effects of the specific emotion regulation strategies. Results
      indicate that emotion regulation difficulties, and particularly one's subjective
      appraisal of his/her ability to effectively regulate emotions, may be of
      importance to health anxiety. Clinical implications are discussed. 

PMID- 24726242
TI  - A monoclonal antibody ameliorates local inflammation and osteoporosis by
      targeting TNF-alpha and RANKL.
AB  - This study aimed to generate a monoclonal antibody (mAb) targeting both tumor
      necrosis factor-alpha (TNF-alpha) and receptor activator of NF-kappaB ligand
      (RANKL) and to evaluate the therapeutic effects of this antibody on acute
      inflammation and osteoporosis. We used hybridoma techniques to generate potential
      mAbs and enzyme-linked immunosorbent assay (ELISA) to determine their
      specificity. Crystal violet staining was performed to measure the effective dose
      of the candidate mAbs. The neutralizing effect of the mAbs was evaluated by TNF
      alpha-mediated cytotoxicity and RANKL-induced osteoclastogenesis assays. We
      further assessed the therapeutic effect of the mAbs in BALB/c mice with
      carrageenan-induced acute inflammation and ovariectomy-induced osteoporosis. We
      successfully generated an IgG1 isotype mAb that recognizes human TNF-alpha and
      RANKL, which we named 8G12. The 50% effective dose of 8G12 was approximately
      1MUg/mL. L929 cells treated with 8G12 exhibited decreased levels of apoptosis
      (20.04% compared to 63.28% in the positive controls). In addition, treatment with
      8G12 inhibited osteoclastogenesis in a dose-dependent manner in vitro.
      Carrageenan-induced paw edema was significantly reduced in the 8G12-treated mice
      compared to the positive controls. Treatment with 8G12 also reduced the number of
      infiltrating leukocytes by more than 50%. The 8G12 treatment not only prevented
      bone loss but also increased the number, thickness and volume of trabeculae and
      reduced trabecular separation in ovariectomized mice. Our data suggest that the
      8G12 effectively neutralizes the bioactivity of TNF-alpha and RANKL, ameliorating
      osteoporosis and inflammation. We therefore propose that 8G12 could be a
      candidate for generating therapeutic antibodies for treating inflammatory bone
      diseases. 

PMID- 24726243
TI  - Anti-oxidant and anti-apoptotic effects of luteolin on mice peritoneal
      macrophages stimulated by angiotensin II.
AB  - PURPOSE: Luteolin, a plant flavonoid, can be found in a variety of plants and
      possesses anti-tumorigenic, anti-mutagenic, anti-oxidant and anti-inflammatory
      properties. However, the protective effects of luteolin on mice peritoneal
      macrophages stimulated by Angiotensin II (Ang II) have not been fully elucidated.
      METHODS AND RESULTS: Mice peritoneal macrophages were confirmed to be strongly
      positive for the macrophage marker CD68. Cell viability was tested after cells
      were pretreated with different concentrations of luteolin (6.25, 12.5 and 25MUM)
      and stimulated by Ang II. Luteolin not only significantly increased the viability
      of macrophages in the presence of Ang II, but also decreased the apoptotic rate,
      up-regulated Bcl-2 expression, and down-regulated Bax expression, thereby raising
      the ratio of Bcl-2 to Bax. In addition, luteolin pretreatment significantly
      increased the activity of SOD and reduced the levels of malondialdehyde (MDA),
      which was up-regulated in the presence of Ang II. This protective effect was also
      seen with Vitamin E (VitE) pretreatment, which was used as a standard control in
      this study. CONCLUSIONS: These data clearly demonstrate that luteolin suppresses
      Ang II-directed oxidative stress and apoptosis on mice peritoneal macrophages.

PMID- 24726244
TI  - An intact signal peptide on dengue virus E protein enhances immunogenicity for
      CD8(+) T cells and antibody when expressed from modified vaccinia Ankara.
AB  - Dengue is a global public health concern and this is aggravated by a lack of
      vaccines or antiviral therapies. Despite the well-known role of CD8(+) T cells in
      the immunopathogenesis of Dengue virus (DENV), only recent studies have
      highlighted the importance of this arm of the immune response in protection
      against the disease. Thus, the majority of DENV vaccine candidates are designed
      to achieve protective titers of neutralizing antibodies, with less regard for
      cellular responses. Here, we used a mouse model to investigate CD8(+) T cell and
      humoral responses to a set of potential DENV vaccines based on recombinant
      modified vaccinia virus Ankara (rMVA). To enable this study, we identified two
      CD8(+) T cell epitopes in the DENV-3 E protein in C57BL/6 mice. Using these we
      found that all the rMVA vaccines elicited DENV-specific CD8(+) T cells that were
      cytotoxic in vivo and polyfunctional in vitro. Moreover, vaccines expressing the
      E protein with an intact signal peptide sequence elicited more DENV-specific
      CD8(+) T cells than those expressing E proteins in the cytoplasm. Significantly,
      it was these same ER-targeted E protein vaccines that elicited antibody
      responses. Our results support the further development of rMVA vaccines
      expressing DENV E proteins and add to the tools available for dengue vaccine
      development. 

PMID- 24726245
TI  - Therapeutic vaccines for tuberculosis--a systematic review.
AB  - For eradication of tuberculosis (TB) by 2050, the declared aim of the Stop TB
      Partnership, novel treatment strategies are indispensable. The emerging epidemic
      of multi-drug resistant (MDR) TB has fuelled the debate about TB vaccines, as
      increasing numbers of patients can no longer be cured by pharmacotherapy. Of
      several proposed modalities, TB vaccines administered in therapeutic manner
      represents a promising alternative, despite the controversial history due to the
      occurrence of exacerbated immune response. A modified concept of immunotherapy is
      required in order to justify further exploration. In this paper we systematically
      reviewed the most advanced therapeutic vaccines for TB. We address the rationale
      of immunotherapeutic vaccination combined with optimized pharmacotherapy in
      active TB. We summarize preclinical and patient data regarding the five most
      advanced therapeutic vaccines currently in the pipeline. Of the five products
      that have been tested in animal models and in humans during active or latent TB,
      the quality of the published clinical reports of two of these products justify
      further studies in patients with active TB. This systematic review fuels further
      clinical evaluation eventually including head-to-head comparative studies. 

PMID- 24726246
TI  - Two-dose strategies for human papillomavirus vaccination: how well do they need
      to protect?
AB  - BACKGROUND: Two-dose human papillomavirus (HPV) vaccine schedules may provide
      short-term protection but their long-term population impact is unknown. METHODS:
      Two models of HPV transmission and associated cervical disease (squamous and
      glandular, neoplasia and cancer) were fitted to data from England and Canada on
      HPV epidemiology, sexual behaviour, cervical screening outcomes and cervical
      cancer incidence. RESULTS: Models suggest that at 40-80% coverage, if two-dose
      schedules protect vaccinees for 20 years, then the benefits of the third dose are
      small. If two doses protect for 10 years, then the third dose may prevent as many
      cancers as the first two. At 80% coverage, numbers needed to receive a third dose
      to prevent an additional cancer are 5900-110,000 (England), 3000-5100 (Canada)
      with 20 years two-dose protection, and 2000-5300 (England), 760-950 (Canada) with
      10 years two-dose protection. CONCLUSION: Results enable decision makers to
      quantify risks associated with two-dose schedules despite remaining uncertainties
      in vaccine duration and cross-protection.

PMID- 24726247
TI  - Does oral polio vaccine at birth affect the size of the thymus? Observations
      within a randomized trial.
AB  - BACKGROUND: There is increasing evidence that vaccines have an effect on general
      mortality which goes beyond specific disease protection. Oral polio vaccine (OPV)
      is widely used in low-income countries, but in observational studies in Guinea
      Bissau we observed that not receiving OPV at birth was associated with reduced
      overall male infant mortality and enhanced immune response to BCG vaccine. We
      therefore initiated a randomized trial to test the overall effect of OPV at birth
      (OPV0). OBJECTIVE: A small thymic gland is a predictor of mortality in high
      mortality settings. Within the trial we aimed to test whether no-OPV0 was
      associated with increased thymic size. METHODS: In 511 normal birth weight
      infants who were randomized to receive or not receive OPV0, thymic index and
      thymus/weight index were measured before randomization and after 2 weeks (N=49),
      4 weeks (N=308) or 6 weeks (N=27). The association between OPV0 and the log
      transformed thymic size indicators were analyzed in ANCOVA models with thymic
      size at follow-up as the outcome and adjusting for thymic size at enrollment and
      age at follow-up. Estimates were reported as geometric mean ratios (GMR) with 95%
      confidence intervals, comparing no-OPV0 to OPV0. RESULTS: No-OPV0 was not
      associated with thymic index after 2 weeks (GMR: 1.14 (0.99-1.30)), after 4 weeks
      (GMR: 0.98 (0.93-1.05)) or after 6 weeks (GMR: 1.00 (0.81-1.23)). However, no
      OPV0 was associated with increased thymus/weight index after 2 weeks (GMR: 1.22
      (1.06-1.40)), but the effect was not seen after 4 weeks (GMR: 0.97 (0.92-1.03))
      and 6 weeks (GMR: 0.99 (0.82-1.19)). There were no strong sex-differences.
      DISCUSSION: Overall there was no effect on thymic size of OPV0 when administered
      with BCG. The results could indicate that if an effect occurs, it is only within
      the first weeks after vaccination.

PMID- 24726248
TI  - Immune response to Bordetella pertussis is associated with season and
      undernutrition in Senegalese children.
AB  - BACKGROUND: While vaccines elicit a protective response in most recipients,
      studies suggest that environmental and nutritional factors can influence the
      strength of the individual response to immunization and to subsequent natural
      infectious challenges. METHODS: We conducted a longitudinal survey in Senegal to
      assess the individual response to B. pertussis, a respiratory disease against
      which Senegalese children are vaccinated before the age of one
      (Clinicaltrials.gov ID: NCT01545115). A cohort of 203 children aged 1-9 from four
      villages of the Senegal River Valley was followed-up for 14 months (October 2008
      January 2010). During that period, four visits have been made to the villages to
      assess the immunological and nutritional status of these children and to
      determine risk factors involved in the modulation of their humoral immune
      response to B. pertussis toxin. RESULTS: A multivariate model has demonstrated
      that birth season and nutritional status appeared to modulate humoral response to
      pertussis toxin. Moreover, response to B. pertussis was dependent on age, village
      and time of visit. CONCLUSIONS: These results are consistent with the hypothesis
      that environmental and nutritional factors modulate children's response to
      pertussis following natural infection or vaccination.

PMID- 24726249
TI  - Anaphylaxis after vaccination of children: review of literature and
      recommendations for vaccination in child and school health services in Belgium.
AB  - BACKGROUND: Concerns about the very small, but real risk of anaphylaxis after
      vaccination, has given rise to specific questions about the safe administration
      of vaccines to children and adolescents in the context of preventive settings
      (i.e. well baby clinics and school health services). As a support to preventive
      health professionals a guideline based on scientific evidence and supported by
      professional consensus was developed in Belgium. METHODS: First, a draft of
      guideline was written based on a review of international literature. Second,
      through several rounds of consultation professional consensus about the document
      was obtained across the Belgian communities and professional groups, and in a
      final version endorsed by the Belgian Superior Health Council in July 2012.
      RESULTS: In a literature overview information is given about the definition of
      anaphylaxis, allergens in vaccines potentially causing anaphylaxis, published
      incidence rates of anaphylaxis after vaccination, and strategies for first-aid
      management of anaphylaxis. The Belgian guideline on the prevention of anaphylaxis
      after vaccination includes recommendations on prevaccination risk assessment, the
      content of the emergency kit, measures to be taken after vaccination,
      differential diagnosis and first-aid management of anaphylaxis. CONCLUSION: The
      guideline, summarized as a flowchart for the prevention and first-aid management
      of anaphylaxis, is considered as the actual state of the art in Belgium for
      vaccination of children and youngsters in preventive health services, and may
      inspire governmental bodies and/or professional groups in other countries to
      adopt similar recommendations.

PMID- 24726250
TI  - Duration of the protective immune response after prime and booster vaccination of
      yearlings with a live modified cold-adapted viral vaccine against equine
      influenza.
AB  - We previously created a live vaccine against equine influenza based the new
      reassortant cold-adapted (Ca) strain A/HK/Otar/6:2/2010. The live vaccine
      contains surface proteins (HA, NA) from the wild-type virus
      A/equine/Otar/764/2007 (N3N8; American Lineage Florida Clade 2), and internal
      proteins (PB2, PB1, PA, NP, M, NS) from the attenuated Ca donor virus A/Hong
      Kong/1/68/162/35CA (H3N2). To determine the safety and duration of the protective
      immune responses, 90 yearlings were intranasally vaccinated in single mode,
      double mode at an interval of 42 days (10(7.0) EID50/animal for both
      vaccinations), or with PBS (control group). Ten animals from each group were
      challenged with the homologous wild-type virus A/equine/Otar/764/07 (N3N8) at 1,
      2, 3, 4, 5, 6, 9 and 12 months after vaccination. Similarly, 10 animals from each
      group were challenged with the heterologous wild-type virus A/equine/Sydney/2888
      8/07 (N3N8; American Lineage Florida Clade 1) 12 months after vaccination. The
      vaccine was completely safe, and single intranasal vaccination of yearlings was
      capable of inducing statistically significant (from P=0.03 to P<0.0001) clinical
      and virological protection against the homologous virus; however, only double
      mode vaccination generated significant (from P=0.02 to P<0.0001) protection
      against the heterologous virus at 12 months (observation period). Interestingly,
      this vaccine enables the differentiation of infected and vaccinated animals. On
      this basis of this study, we recommend double intranasal administration of this
      vaccine at an interval of 42 days in veterinary practice. 

PMID- 24726251
TI  - Healthcare providers as sources of vaccine-preventable diseases.
AB  - Vaccine-preventable infectious diseases may be introduced into the healthcare
      setting and pose a serious risk to vulnerable populations including
      immunocompromised patients. Healthcare providers (HCPs) are exposed to these
      pathogens through their daily tasks and may serve as a reservoir for ongoing
      disease transmission in the healthcare setting. The primary method of protection
      from work-related infection risk is vaccination that protects not only an
      individual HCP from disease, but also subsequent patients in contact with that
      HCP. Individual HCPs and healthcare institutions must balance the ethical and
      professional responsibility to protect their patients from nosocomial
      transmission of preventable infections with HCP autonomy. This article reviews
      known cases of HCP-to-patient transmission of the most common vaccine-preventable
      infections encountered in the healthcare setting including hepatitis B virus,
      influenza virus, Bordetella pertussis, varicella-zoster virus, measles, mumps and
      rubella virus. The impact of HCP vaccination on patient care and current
      recommendations for HCP vaccination against vaccine-preventable infectious
      diseases are also reviewed. 

PMID- 24726252
TI  - Noninvasive risk stratification of patients with transthyretin amyloidosis.
AB  - OBJECTIVES: We sought to evaluate noninvasive parameters by electrocardiography,
      echocardiography, technetium-99m-3,3-diphosphono-1,2-propanodicarboxylic acid
      ((99m)Tc-DPD) scintigraphy, and cardiac magnetic resonance for the prediction of
      all-cause mortality in patients with cardiac transthyretin amyloidosis (ATTR).
      BACKGROUND: ATTR may present with highly variable symptoms, including
      polyneuropathy and cardiomyopathy, the latter being associated with a poor
      outcome. However, data on noninvasive risk stratification of ATTR are limited.
      METHODS: A total of 70 patients with ATTR were evaluated by echocardiography,
      cardiac biomarkers, and (99m)Tc-DPD scintigraphy. Cardiac magnetic resonance was
      performed in 30 patients. Echocardiographic findings and plasma levels of
      biomarkers were correlated with results of quantitative analysis of scintigraphy
      using a region-of-interest technique (whole-body as well as heart tracer
      retention). Receiver-operating characteristic (ROC) analysis was performed to
      calculate a cutoff value of (99m)Tc-DPD scintigraphy for heart retention for the
      diagnosis of cardiac amyloid involvement with the highest sensitivity and
      specificity. Univariate and multivariate analyses were performed in patients with
      cardiac involvement (n = 60) to determine noninvasive predictors of all-cause
      mortality. RESULTS: Scintigraphy findings correlated with morphological
      (interventricular septum thickness, left ventricular hypertrophy index) as well
      as functional (mitral annular systolic velocity, mitral/tricuspid annular plane
      systolic excursion) findings, cardiac biomarkers, renal function, and late
      gadolinium enhancement. The ROC-derived cutoff for the detection of cardiac
      amyloidosis by scintigraphic heart tracer retention was 4.8%. Univariate Cox
      regression revealed N-terminal pro-B-type natriuretic peptide, troponin T, mitral
      annular plane systolic excursion, and left ventricular hypertrophy index as
      predictors of all-cause mortality. However, on multivariate analysis, troponin T
      remained the only independent predictor of survival. The ROC-derived cutoff value
      of troponin T predicting all-cause mortality with the highest sensitivity (80.0%)
      and specificity (68.7%) was 0.0375 ng/l. CONCLUSIONS: Quantitative analysis of
      tracer retention is capable of characterizing the severity of cardiac involvement
      in ATTR. By multivariate analysis, troponin T remained the only independent
      predictor of survival.

PMID- 24726253
TI  - LA emptying fraction improves diagnosis of paroxysmal AF after cryptogenic
      ischemic stroke: results from the SURPRISE study.

PMID- 24726254
TI  - Vasodilator stress perfusion CMR imaging is feasible and prognostic in obese
      patients.
AB  - OBJECTIVES: This study sought to determine feasibility and prognostic performance
      of stress cardiac magnetic resonance (CMR) in obese patients (body mass index
      [BMI] >=30 kg/m(2)). BACKGROUND: Current stress imaging methods remain limited in
      obese patients. Given the impact of the obesity epidemic on cardiovascular
      disease, alternative methods to effectively risk stratify obese patients are
      needed. METHODS: Consecutive patients with a BMI >=30 kg/m(2) referred for
      vasodilating stress CMR were followed for major adverse cardiovascular events
      (MACE), defined as cardiac death or nonfatal myocardial infarction. Univariable
      and multivariable Cox regressions for MACE were performed to determine the
      prognostic association of inducible ischemia or late gadolinium enhancement (LGE)
      by CMR beyond traditional clinical risk indexes. RESULTS: Of 285 obese patients,
      272 (95%) completed the CMR protocol, and among these, 255 (94%) achieved
      diagnostic imaging quality. Mean BMI was 35.4 +/- 4.8 kg/m(2), with a maximum
      weight of 200 kg. Reasons for failure to complete CMR included claustrophobia (n
      = 4), intolerance to stress agent (n = 4), poor gating (n = 4), and declining
      participation (n = 1). Sedation was required in 19 patients (7%; 2 patients with
      intravenous sedation). Sixteen patients required scanning by a 70-cm-bore system
      (6%). Patients without inducible ischemia or LGE experienced a substantially
      lower annual rate of MACE (0.3% vs. 6.3% for those with ischemia and 6.7% for
      those with ischemia and LGE). Median follow-up of the cohort was 2.1 years. In a
      multivariable stepwise Cox regression including clinical characteristics and CMR
      indexes, inducible ischemia (hazard ratio 7.5; 95% confidence interval: 2.0 to
      28.0; p = 0.002) remained independently associated with MACE. When patients with
      early coronary revascularization (within 90 days of CMR) were censored on the day
      of revascularization, both presence of inducible ischemia and ischemia extent per
      segment maintained a strong association with MACE. CONCLUSIONS: Stress CMR is
      feasible and effective in prognosticating obese patients, with a very low
      negative event rate in patients without ischemia or infarction.

PMID- 24726255
TI  - Molecular and cellular correlates of cardiac function in end-stage DCM: a study
      using speckle tracking echocardiography.
AB  - OBJECTIVES: We sought to compare the effects of interstitial fibrosis and
      myocardial force generation/relaxation elements on left ventricular (LV) function
      in patients with end-stage dilated cardiomyopathy (DCM). BACKGROUND: Interstitial
      fibrosis is common in patients with advanced heart failure. However, the extent
      to which it affects cardiac function remains unclear. METHODS: Longitudinal,
      radial, and circumferential strain; strain rate during systole (SRS) and strain
      rate during early diastole (SRE); LV volume; LV ejection fraction; mean pulmonary
      capillary wedge pressure (PCWP); and e' were measured in 20 DCM patients. Myocyte
      diameter, interstitial fibrosis, messenger ribonucleic acid (mRNA) levels of
      molecules implicated in fibrosis and function (transforming growth factor beta,
      titin [TTN] N2B and N2BA isoforms, collagen type I, collagen type III,
      sarcoplasmic reticulum Ca(2+)-ATPase [SERCA2a], phospholamban [PLB], and protein
      levels of SERCA2a, phosphorylated PLB, and Smad2/3) were correlated with strain
      from 4 regions per patient (LV apex, midlateral, septum, and right ventricular
      free wall) as well as LV global function. In another group of 8 DCM patients, we
      evaluated LV structure and function before and after LV assist device. RESULTS:
      Significant correlations were present among ejection fraction, e' velocity, PCWP,
      LV end-diastolic volume/PCWP ratio, strain, SRS, SRE, and mRNA expression of TTN
      N2B, N2BA, SERCA2a, PLB, and protein levels of SERCA2a and phosphorylated PLB (r
      = 0.53 to 0.95, p < 0.05). Weak to no associations were present between strain
      and interstitial fibrosis and its molecular determinants. In patients with repeat
      studies, regional strain and SRE best tracked the changes in mRNA expression of
      TTN isoform N2BA and mRNA and protein expression of SERCA2a. CONCLUSIONS: LV
      systolic and diastolic functions in DCM are primarily associated with myocardial
      force generation/relaxation elements.

PMID- 24726256
TI  - Comprehensive dobutamine stress CMR versus echocardiography in LBBB and suspected
      coronary artery disease.
AB  - OBJECTIVES: This study aimed to compare dobutamine stress cardiac magnetic
      resonance (DSCMR) with dobutamine stress echocardiography (DSE) in patients with
      left bundle branch block (LBBB) and suspected coronary artery disease (CAD).
      BACKGROUND: Noninvasive diagnosis of CAD in patients with pre-existent LBBB is
      difficult because single-photon emission computed tomography and stress
      echocardiography both have limitations. We hypothesized that a comprehensive
      DSCMR examination including cine, perfusion, and late gadolinium enhancement
      imaging would be more accurate than DSE, thus potentially reducing the number of
      unnecessary invasive coronary angiograms. METHODS: We prospectively evaluated 82
      consecutive patients with LBBB referred to our cardiology clinic for
      investigation of suspected CAD. All 82 patients underwent DSE, DSCMR, and
      invasive quantitative coronary angiography within 14 days. We compared the
      diagnostic accuracy of DSE, CMR cine imaging, the additive value of first-pass
      perfusion, and late gadolinium enhancement. In the comprehensive examination, a
      positive result was adjudged as the presence of either subendocardial or
      transmural late gadolinium enhancement with or without inducible peri-infarct
      ischemia or an inducible perfusion defect corresponding to an inducible regional
      wall motion abnormality. RESULTS: CMR cine imaging (regional wall motion
      abnormalities) had higher specificity, negative predictive value, and overall
      diagnostic accuracy than did DSE (87.5% vs. 72.9%; 80.8% vs. 67.3%; and 80.4% vs.
      72.0%, respectively), although sensitivity was the same (72.0%). The addition of
      first-pass stress perfusion and late gadolinium enhancement (scar) further
      improved diagnostic confidence (sensitivity 82.4%, specificity 95.8%, positive
      predictive value 93.3%, negative predictive value 88.5%, and diagnostic accuracy
      90.2%). CONCLUSIONS: DSCMR is a safe procedure and has greater diagnostic
      accuracy than does DSE in assessing patients with suspected CAD and LBBB. A
      comprehensive examination with the addition of perfusion and late gadolinium
      enhancement to CMR cine imaging significantly boosted specificity and
      sensitivity, making DSCMR a reliable alternative to invasive quantitative
      coronary angiography in this group of patients.

PMID- 24726257
TI  - Lab-on-a-chip technologies for stem cell analysis.
AB  - The combination of microfabrication-based technologies with cell biology has laid
      the foundation for the development of advanced in vitro diagnostic systems
      capable of analyzing cell cultures under physiologically relevant conditions. In
      the present review, we address recent lab-on-a-chip developments for stem cell
      analysis. We highlight in particular the tangible advantages of microfluidic
      devices to overcome most of the challenges associated with stem cell
      identification, expansion and differentiation, with the greatest advantage being
      that lab-on-a-chip technology allows for the precise regulation of culturing
      conditions, while simultaneously monitoring relevant parameters using embedded
      sensory systems. State-of-the-art lab-on-a-chip platforms for in vitro assessment
      of stem cell cultures are presented and their potential future applications
      discussed. 

PMID- 24726258
TI  - A new cholesterol biosynthesis and absorption disorder associated with epilepsy,
      hypogonadism, and cerebro-cerebello-bulbar degeneration.
AB  - BACKGROUND: Cholesterol is one of the main components of human cell membranes and
      constitutes an essential substance in the central nervous system, endocrine
      system, and its hormones, including sex hormones. PATIENT: A 19-year-old male
      patient presented with failure to thrive, psychomotor deterioration, intractable
      epilepsy, hypogonadism, and cerebro-cerebello-bulbar degeneration. His serum
      level of cholesterol was low, ranging from 78.7 to 116.5 mg/dL. RESULTS: The
      serum concentrations of intermediates in the cholesterol biosynthesis pathway,
      such as 7-dehydrocholesterol, 8-dehydrocholesterol, desmosterol, lathosterol, and
      dihydrolanosterol, were not increased. In addition, the levels of the urinary
      cholesterol biosynthesis marker mevalonic acid, the serum cholesterol absorption
      markers, campesterol and sitosterol, and the serum cholesterol catabolism marker,
      7alpha-hydroxycholesterol, were all low. CONCLUSIONS: A serum biomarker analysis
      indicated that the patient's basic abnormality differed from that of Smith-Lemli
      Opitz syndrome and other known disorders of cholesterol metabolism. Therefore,
      this individual may have a new metabolic disorder with hypocholesterolemia
      because of decreased biosynthesis and absorption of cholesterol.

PMID- 24726259
TI  - Pulmonary arteriovenous malformation with actinomycotic brain abscess: a rare
      association.

PMID- 24726260
TI  - [Lipid kinetics during dual antiviral therapy in patients with chronic hepatitis
      C].
AB  - BACKGROUND AND OBJECTIVE: We analyzed baseline and kinetic characteristics of
      lipid metabolism during the first month of bitherapy in patients with chronic
      hepatitis C genotype 1 (CHC-1). PATIENTS AND METHODS: A longitudinal, prospective
      study including 99 naive CHC-1 patients with liver biopsy who were treated with
      bitherapy. Our patients were assigned to one of 5 different "degrees of lipid
      requirement" that we established depending on the degree of liver fibrosis,
      baseline viral load and infectivity ratio (ratio between the median level of
      triglycerides and high densitity lipoproteins-cholesterol during the first
      month). The goal was to achieve "a favorable lipid metabolism" (FLM) by
      establishing a necessary minimum level of low density lipoproteins (LDL)
      cholesterol during this period for each one of them. We also analyzed the
      relationship with the rate of sustained virological response. RESULTS: Patients
      with liver fibrosis F3-F4 who had higher baseline levels of LDL-cholesterol
      achieved higher rates of sustained virological response. Those patients who had a
      lower value of infectivity ratio and median levels of LDL-cholesterol during the
      first month of bitherapy also achieved higher rates of sustained virological
      response: SVR group 100 (23) mg/dl against non-SVR group: 89 (28) mg/dl; odds
      ratio 1.1; 95% confidence interval (1.0-1.2); P<.05, these differences being more
      significant for genotype IL-28B-CC (P=.013). Patients with sustained virological
      response had higher rates of FLM. CONCLUSIONS: Not every patient with CHC-1 has
      the same lipid kinetics during the first month of bitherapy, and it is necessary
      to achieve a sustained virological response and/or a FLM to keep higher plasma
      levels of LDL-cholesterol during this period. Those subjects without FLM could
      benefit from statins.

PMID- 24726261
TI  - [Adult pulmonary Langerhans' cell histiocytosis: approach to the reality of the
      Spanish population].
AB  - BACKGROUND AND OBJECTIVE: Pulmonary Langerhans cell histiocytosis (PLCH) is a
      rare respiratory disease closely associated with smoking. The aim of the study is
      to know the reality of PLCH in the Catalonian population. MATERIAL AND METHODS:
      We included all patients diagnosed of PLCH in 8 different Catalonian hospitals
      from April 2011 to December 2012. Epidemiologic, clinical, radiological,
      functional, diagnostic and therapeutic variables were collected, both at the
      beginning and at the last visit of the process. RESULTS: Thirty two patients were
      included. Overall, patients were middle-aged (38 years), with no gender
      predominance. Most of them were smokers (71.9%). The main pulmonary function
      values (forced vital capacity 75.9%, forced expiratory volume in one second
      68.9%, diffusing capacity of the lung for carbon monoxide 59.6%) and radiological
      findings (cysts 89.7%, nodules 60.3%) showed no significant changes during
      evolution. However, the disease progressed with a worsening lung function in
      34.4% of cases. The analysis of the functional outcome (forced vital capacity,
      forced expiratory volume in one second, and diffusing capacity of the lung for
      carbon monoxide) did not reveal significant differences according to the
      persistence or not of smoking (P<0.05). CONCLUSION: Our patients with PLCH had
      similar clinical and radiological characteristics to those described in other
      populations. The results observed regarding the relationship with smoking suggest
      that there may be other factors beyond smoking, which influence on the evolution
      of the disease. It therefore seems advisable to design prospective studies to
      investigate this aspect.

PMID- 24726262
TI  - Tumor deposits in gastric carcinomas.
AB  - We performed this study to examine the prevalence of tumor deposits (TD) in
      gastric adenocarcinomas (GACa), and the relevance of their presence, size and
      type to clinical outcome. Ninety-six patients, histopathologically diagnosed as
      GACa following a total/subtotal gastrectomy were included, and clinicopathologic
      data were recorded. Due to the statistical analysis, the majority of TD(+) cases
      were of intestinal type and showed vascular invasion. In these cases, the
      incidence of local recurrence was significantly higher. The majority of GACa of
      intestinal type with TD were of high grade and showed vascular invasion.
      Recurrence and death were more commonly encountered among them. The recurrence
      free survival (RFS) was significantly shorter in patients with TDs, which was
      also confirmed by multivariate analysis, and there was a significant difference
      between both RFS and overall survival of TD(+) and TD(-) cases of intestinal type
      GACa. In conclusion, in this study, we demonstrate that TDs are not infrequently
      observed in GACa, they are more commonly associated with the intestinal type and
      vascular invasive gastric cancers. Our study shows the prognostic impact of TDs,
      especially regarding the RFS. Therefore, the documentation of TDs might be
      considered for prospective studies, especially for the intestinal type GACa, a
      shortcoming of this study.

PMID- 24726263
TI  - Role of lymphovascular invasion and immunohistochemical expression of IMP3 in the
      risk stratification of superficially invasive pT1 esophageal adenocarcinoma.
AB  - BACKGROUND: A problem in the management of patients with Barrett's esophagus
      related pT1 esophageal adenocarcinoma is to distinguish those who should be
      treated conservatively (endoscopic mucosal resection and/or radiofrequency
      ablation) from those who require esophago-gastrectomy. Recently, lymphovascular
      invasion (LVI) has emerged as one of the best predictors of regional lymph node
      metastasis (LNM) and recurrence-free survival (RFS) in pT1 EAC. However, LVI may
      be underestimated, both because of interobserver variability and incomplete
      sampling. The aim of our study was to correlate the presence of LVI, with the
      immunohistochemical expression of IMP3 in pT1 EAC and assess their role in
      further stratifying these lesions into high and low risk groups based on the
      potential for lymph node metastasis and poor outcome. DESIGN: Depth of invasion,
      assessed in five sublevels (m2, m3, sm1, sm2, and sm3), LVI, and expression of
      IMP3 were studied in 30 patients who underwent esophagogastrectomy for pT1 EAC
      (2001-2010) at Hartford Hospital, and correlated with LNM and RFS. IMP3 was
      considered positive when expressed in >50% of the malignant cells with an
      intensity of stain of 2-3+. RESULTS: Ten of 18 (55.5%) cases with IMP3 expression
      demonstrated LVI and 2/10 (20%) showed LNM and died of disease. In contrast, none
      of the 12 IMP3 negative cases showed LVI (p<0.004; 2-tailed Fisher exact test) or
      had LNM/DOD. CONCLUSIONS: In pT1 EAC, (1) based on IMP3 expression, pT1 EAC may
      be divided into high risk (LVI+/IMP3+) and low risk (LVI-/IMP3-) categories. (2)
      Absence of IMP3 expression is associated with a significantly reduced risk of LVI
      (Negative Predictive Value: 100%). (3) Since identifying lymphovascular invasion
      and other morphological parameters is prone to significant inter-observer
      variation, IMP3 may be useful as an ancillary marker especially in these pT1
      lesions in predicting their clinical behavior, the risk stratification and
      potentially on the type of treatment.

PMID- 24726264
TI  - [Impact of mobile neuroendoscopy in the development of neurosurgery in Africa. An
      original Spanish model].

PMID- 24726265
TI  - Intraoperative endoscopic removal of a duodenal bezoar in a patient with
      intestinal malrotation.

PMID- 24726266
TI  - Extraosseous plasmacytoma of the stomach.

PMID- 24726267
TI  - Expression of cancer stem cell markers in basal and penta-negative breast
      carcinomas--a study of a series of triple-negative tumors.
AB  - PURPOSE: Breast cancer is a heterogeneous disease. Immunohistochemistry has given
      rise to triple-negative carcinoma (TNC). Concomitantly, biological origins of
      neoplasia and its heterogeneity has been strongly debated in cancer stem cells
      (CSC) theme. This study investigates the prevalence of basal (BCC) and penta
      negative carcinomas (5NC) in TNC and establishes associations with CSC
      (CD44CD24). MATERIALS AND METHODS: 94 TNC were tested for CK5/6, HER1, CD44 and
      CD24, evaluated by a simple immunohistochemistry score and correlated with
      clinicopathological and survival data. RESULTS: BCC had higher tumor grades than
      5NC (p=0.004). CD44 negativity (p=0.007) and CD44(-)CD24(+) phenotype (p=0.013)
      were associated with less vascular invasion amongst TNC. CD44 expression was
      associated with BCC (p=0.007). CD44(-)CD24(-/low) phenotype was associated with
      5NC. None of the variables were associated with clinical outcome. CONCLUSION: BCC
      and 5NC are closely related tumor subtypes. CD44(-)CD24(-/low) phenotype was
      associated with 5NC and CD44(-)CD24(+) phenotype was associated with vascular
      invasion. These results require histogenetic confirmation in larger studies.

PMID- 24726268
TI  - Amplification of EVI1 on cytogenetically cryptic double minutes as new mechanism
      for increased expression of EVI1.
AB  - In acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS), increased
      expression of EVI1 (ecotropic virus integration site 1) was found to be
      associated with adverse prognosis. Although increased expression of the EVI1 gene
      is mainly caused by chromosomal rearrangements involving chromosome band 3q26,
      where EVI1 is located, it can also be identified in cases without these
      rearrangements. The mechanisms that cause increased EVI1 expression in the
      absence of 3q26 rearrangements remain unclear. Here, we present four cases with
      increased EVI1 expression due to EVI1 amplification on cytogenetically cryptic
      double minutes (dmin). The dmin are small acentric chromosome structures and were
      observed in about 1% of AML and MDS. We investigated the four cases by
      conventional cytogenetics, fluorescence in situ hybridization, and array
      comparative genomic hybridization. Furthermore, EVI1 expression was measured by
      quantitative reverse transcriptase-PCR. By conventional chromosome analysis, the
      EVI1 dmin cannot be detected, due to the small size of the amplicons of 0.49-0.78
      Mbp. Median % EVI1/ABL expression was 88.9% and therefore comparable to the
      median % EVI1/ABL expression of patients with EVI1 rearrangements. In conclusion,
      EVI1 amplification on cytogenetically cryptic dmin causes increased expression of
      EVI1 and is a new mechanism that causes increased EVI1 expression without a 3q26
      rearrangement.

PMID- 24726269
TI  - Translocation t(2;7)(p11;q21) associated with the CDK6/IGK rearrangement is a
      rare but recurrent abnormality in B-cell lymphoproliferative malignancies.
AB  - Structural abnormalities of chromosome 7q have been regularly reported in chronic
      B-cell lymphoproliferative disorders. They include chromosomal translocations
      involving 7q21, leading to overexpression of the CDK6 gene. Three different
      translocations, t(7;14)(q21;q32), t(7;22)(q21;q11), and t(2;7)(p11;q21), leading
      to the juxtaposition of the CDK6 gene with a immunoglobulin gene enhancer during
      B-cell differentiation, have been described. In the past 2 years, we identified
      three patients with lymphoproliferative malignancy associated with a
      t(2;7)(p11;q21). Fluorescent in situ hybridization using an IGK probe and a
      library of bacterial artificial chromosome (BAC) clones located in bands 7q21.2
      and 7q21.3, containing CDK6, revealed that the telomeric part of the IGK probe
      was translocated on the der(7) within a 51-kb region upstream of the
      transcriptional start site of CDK6. A total of 23 patients with indolent B-cell
      lymphoproliferative disorders and juxtaposition of the IG and CDK6 genes,
      including 20 with IGK and CDK6 juxtaposition, have been reported thus far. This
      rearrangement leads to the overexpression of CDK6, which encodes a cyclin
      dependent protein kinase involved in cell cycle G1 phase progression and G1/S
      transition. 

PMID- 24726271
TI  - Bile acids in cholestasis: bad for the liver, not so good for the kidney.
AB  - The elegant paper by Fickert et al. on bile duct ligated mice provides convincing
      evidence for the hypothesis that bile acids retained in the serum during
      cholestasis and excreted through the kidneys are toxic to collecting duct cells.
      The authors propose that bile acids initiate a chain of reactions leading to
      tubulointerstitial nephritis and fibrosis. Mice with cholestasis were protected
      by prefeeding with the hydrophilic bile acid norursodeoxycholic acid, an
      observation which suggests a potential therapeutic option for cholemic
      nephropathy. 

PMID- 24726270
TI  - The use of narrative sampling in the assessment of social cognition: the
      Narrative of Emotions Task (NET).
AB  - Social cognitive deficits in schizophrenia are well documented and related to
      functional outcome. Current social cognition measures are often not
      psychometrically validated, too heterogeneous for standardization, and focus
      principally on one domain of social cognition rather than the simultaneous
      activation of multiple domains. Also, few if any allow for personalization of
      stimuli and interpretation of personally evocative events. An alternative
      methodology that addresses these limitations is the analysis of samples of
      personal narratives. The present study evaluates the psychometric properties of a
      measure called the Narrative of Emotions Task (NET). The NET was used to assess
      the performance of participants with a diagnosis of schizophrenia or
      schizoaffective disorder and nonclinical controls. Use of the NET revealed
      significant impairments in the emotional narratives of participants with
      schizophrenia. Various NET indices were significantly related to current measures
      of theory of mind and emotion perception, as well as a social skills role-play,
      but were not related to measures of attributional style or clinician-rated
      functioning scales. Overall, the NET's psychometric properties justify further
      use of the narrative sampling method of social cognition assessment in this
      population. 

PMID- 24726272
TI  - Gastric ectopic pancreas complicated by formation of a pseudocyst.

PMID- 24726273
TI  - Pediatric non-alcoholic fatty liver disease: recent advances.
AB  - Central obesity represents the major factor responsible for NAFLD, but several
      immunological and endocrinological mechanisms are involved in fatty infiltration
      in the liver, inflammation and fibrosis. Gut microbiota and genetic factors were
      recently indicated as major players in liver injury. Loss of weight and physical
      activity represent till now the cornerstone of treatment, but they are very
      difficult to obtain and to maintain. Several pharamocotherapeutic approaches
      including insulin sensitizers, omega-3 fatty acids and vitamin E have been
      extensively studied in randomized trials, but final conclusions still could not
      be formulated. Therefore, new treatments based on pathogenetic mechanisms leading
      to NAFLD are under evaluation to establish the effective pharmacological therapy
      of this disorder. 

PMID- 24726274
TI  - Light energy allocation at PSII under field light conditions: how much energy is
      lost in NPQ-associated dissipation?
AB  - In the field, plants are exposed to fluctuating light, where photosynthesis
      occurs under conditions far from a steady state. Excess energy dissipation
      associated with energy quenching of chlorophyll fluorescence (qE) functions as an
      efficient photo-protection mechanism in photosystem II. PsbS is an important
      regulator of qE, especially for the induction phase of qE. Beside the regulatory
      energy dissipation, some part of energy is lost through relaxation of excited
      chlorophyll molecules. To date, several models to quantify energy loss through
      these dissipative pathways in PSII have been proposed. In this short review, we
      compare and evaluate these models for PSII energy allocation when they are
      applied to non-steady state photosynthesis. As a case study, an investigation on
      energy allocation to qE-associated dissipation at PSII under non-steady state
      photosynthesis using PsbS-deficient rice transformants is introduced. Diurnal and
      seasonal changes in PSII energy allocation in rice under natural light are also
      presented. Future perspective of studies on PSII energy allocation is discussed. 

PMID- 24726275
TI  - Double-bundle PCL reconstruction using autogenous quadriceps tendon and
      semitendinous graft: surgical technique with 2-year follow-up clinical results.
AB  - OBJECTIVE: The objective of this study was to evaluate the results obtained from
      posterior cruciate ligament (PCL) reconstruction with the double femoral tunnel
      technique, using quadriceps tendon and semitendinous autograft, in patients with
      isolated PCL tears or PCL tears associated with other ligament lesions, 2 years
      after surgery. METHODS: The study included 14 patients with isolated PCL lesions
      and 20 with combined ligament lesions, who underwent PCL reconstruction using the
      double femoral tunnel technique and were evaluated 24 months after surgery using
      the International Knee Documentation Committee (IKDC) and Lysholm scores, a KT
      1000 arthrometer, and the graduation of the posterior drawer test. RESULTS: Knees
      were considered normal ("A") or nearly normal ("B") in 92.9% of patients with
      isolated lesions and in 95.0% of patients with combined tears, according to the
      IKDC score. Good or excellent results were obtained in 100% of patients in both
      groups according to the Lysholm score. Absence or outstanding reduction of
      posterior tibial translation was seen in 92.9% of patients with isolated lesions
      and in 100% of patients with combined ligament tears, in the posterior drawer
      evaluation. CONCLUSION: The PCL double femoral tunnel reconstruction technique
      using autografts was effective in restoring posterior knee stability, in isolated
      and/or combined PCL tears, showing remarkable clinical improvement in all
      patients. LEVEL OF EVIDENCE: 2C.

PMID- 24726276
TI  - Percutaneous reconstruction of patellar tendon using semitendinosus tendon in
      chronic patellar tendon injury--case series and outcome.
AB  - BACKGROUND: Chronic patellar tendon injuries are rare. Patients with these
      debilitating injuries present with extension lag and quadriceps atrophy.
      Diagnosis is usually made on a clinical background. Various methods of
      reconstruction of torn patellar tendon have been described and the ideal method
      of treatment is a matter of debate. METHODS: We retrospectively reviewed the
      medical records of nine patients with chronic patellar tendon injury that came to
      us between June 2006 and July 2012. In all patients, the patellar tendon was
      reconstructed percutaneously using semitendinosus tendon. Picrusting of
      quadriceps was required in two patients to pull the patella down. RESULT: Average
      follow-up was 4.5 years. At final follow-up Lysholm score, Siwek and Rao grading
      were good to excellent in all patients, and at 12 months, all patients showed
      quadriceps strength 80% or more of opposite quadriceps. CONCLUSION: Percutaneous
      reconstruction of the patellar tendon in chronic patellar tendon injury using
      semitendinosus tendon gives excellent result. Picrusting of quadriceps along with
      lateral release may be required to pull the patella down. LEVEL OF EVIDENCE:
      Level IV.

PMID- 24726277
TI  - Non-functioning pituitary macroadenomas: Benefit from early growth hormone
      substitution after surgery.
AB  - PURPOSE: Data suggests that substitution of GH in GH-deficient patients may
      improve quality-of-life and reduce insufficiency-associated-symptoms. Unlike in
      corticotroph, thyreotroph, or gonadotroph-insufficiency, GH-substitution is
      usually not started within the first 6-12months after surgery. We aimed to
      investigate the effect of early-GH-substitution on body-composition, metabolic
      and pituitary-laboratory-tests, and quality-of-life. METHODS: Data was reviewed
      from 21 adult-patients who were diagnosed with insufficiency of GH-axis using
      insulin-hypoglycemia-test. We retrospectively assessed body-composition,
      metabolic and pituitary-laboratory-tests and quality-of-life for a period of 52
      weeks after pituitary-surgery in patients with early GH-substitution (= treated
      group, 11-patients) and no GH-substitution (= untreated group, 10-patients).
      RESULTS: Follow-up-IGF-I-levels of the treated-group stayed within the normal
      range and differed significantly from the untreated-group. Bioelectrical
      impedance-analysis showed a significant decrease of impedance, a significant
      increase of lean-body-mass and a significant difference in health status in the
      treated group (p<0.05). Average increase in HDL-level was 2.1mg/dl in the
      untreated compared to an average decrease of 0.2mg/dl in the treated-group. Lp(a)
      levels were reduced by 4.1mg/dl in the treated and by 2.7mg/dl in the untreated
      group. Both groups showed an initial-mean-life-satisfaction below average (-0.9
      and -1.2). Within one year after surgery mean-health-status improved in both
      groups. The difference in health-status after 1-year compared to the health
      status of the previous year was statistically different between both groups with
      a greater benefit in the treated-group. Finally there was a trend detectably
      pointing towards an improvement in pituitary-function (LH- and FSH-recovery) if
      GH was substituted. CONCLUSION: Early GH-substitution leads to a significant
      improvement in quality-of-life and body-composition after pituitary-surgery. It
      is possible that pituitary-function recovers more with early-GH-substitution.

PMID- 24726278
TI  - Atomic resolution imaging and spectroscopy of barium atoms and functional groups
      on graphene oxide.
AB  - We present an atomic resolution transmission electron microscopy (TEM) and
      scanning TEM (STEM) study of the local structure and composition of graphene
      oxide modified with Ba(2+). In our experiments, which are carried out at 80kV,
      the acquisition of contamination-free high-resolution STEM images is only
      possible while heating the sample above 400 degrees C using a highly stable
      heating holder. Ba atoms are identified spectroscopically in electron energy-loss
      spectrum images taken at 800 degrees C and are associated with bright contrast in
      high-angle annular dark-field STEM images. The spectrum images also show that Ca
      and O occur together and that Ba is not associated with a significant
      concentration of O. The electron dose used for spectrum imaging results in beam
      damage to the specimen, even at elevated temperature. It is also possible to
      identify Ba atoms in high-resolution TEM images acquired using shorter exposure
      times at room temperature, thereby allowing the structure of graphene oxide to be
      studied using complementary TEM and STEM techniques over a wide range of
      temperatures. 

PMID- 24726279
TI  - Flexible automated platform for blood group genotyping on DNA microarrays.
AB  - The poor suitability of standard hemagglutination-based assay techniques for
      large-scale automated screening of red blood cell antigens severely limits the
      ability of blood banks to supply extensively phenotype-matched blood. With better
      understanding of the molecular basis of blood antigens, it is now possible to
      predict blood group phenotype by identifying single-nucleotide polymorphisms in
      genomic DNA. Development of DNA-typing assays for antigen screening in blood
      donation qualification laboratories promises to enable blood banks to provide
      optimally matched donations. We have designed an automated genotyping system
      using 96-well DNA microarrays for blood donation screening and a first panel of
      eight single-nucleotide polymorphisms to identify 16 alleles in four blood group
      systems (KEL, KIDD, DUFFY, and MNS). Our aim was to evaluate this system on 960
      blood donor samples with known phenotype. Study data revealed a high concordance
      rate (99.92%; 95% CI, 99.77%-99.97%) between predicted and serologic phenotypes.
      These findings demonstrate that our assay using a simple protocol allows
      accurate, relatively low-cost phenotype prediction at the DNA level. This system
      could easily be configured with other blood group markers for identification of
      donors with rare blood types or blood units for IH panels or antigens from other
      systems.

PMID- 24726280
TI  - Combining environment and health information systems for the assessment of
      atmospheric pollution on human health.
AB  - The use of emerging technologies for environmental monitoring with satellite and
      in-situ sensors have become essential instruments for assessing the impact of
      environmental pollution on human health, especially in areas that require high
      spatial and temporal resolution. This was until recently a rather difficult
      problem. Regrettably, with classical approaches the spatial resolution is
      frequently inadequate in reporting environmental causes and health effects in the
      same time scale. This work examines with new tools different levels of air
      quality with sensor monitoring with the aim to associate those with severe health
      effects. The process established here facilitates the precise representation of
      human exposure with the population attributed in a fine spatial grid and taking
      into account environmental stressors of human exposure. These stressors can be
      monitored with innovative sensor units with a temporal resolution that accurately
      describes chronic and acute environmental burdens. The current understanding of
      the situation in densely populated areas can be properly analyzed, before
      commitments are made for reductions in total emissions as well as for assessing
      the effects of reduced trans-boundary fluxes. In addition, the data processed
      here with in-situ sensors can assist in establishing more effective regulatory
      policies for the protection of vulnerable population groups and the satellite
      monitoring instruments permit abatement strategies that are close to real-time
      over large geographical areas. 

PMID- 24726281
TI  - [Use of emergency departments in rural and urban areas in Spain].
AB  - OBJECTIVES: Describe the use of emergency departments (ED), and analyse the
      differences in use between residents in rural and urban areas. MATERIAL AND
      METHODS: Using data from the National Health Survey of 2006 and 2011, the
      profiles of patients with ED visits by population size of place of residence were
      obtained. The variables associated with making one visit to the ED were also
      evaluated, in order to determine the effect of the population size of place of
      residence. RESULTS: A higher use of ED is observed in persons with a higher
      frequency of use of Primary Care and hospital admissions, and increases with
      worse self-perceived health and functional status, with more chronic diseases, in
      people from lower social classes, and younger ages. Adjusting for the other
      variables, residents in larger cities have a higher use of ED than residents in
      rural areas, who show a higher use of public and non-hospital based ED, than
      residents in urban areas. DISCUSSION: There is a higher use of ED by inhabitants
      of urban areas that cannot be justified by a worst health status of that
      population. This tends to indicate that the use of ED is not under-used in rural
      areas, but overused in urban areas.

PMID- 24726282
TI  - Formation of proximal and anterior limb skeleton requires early function of Irx3
      and Irx5 and is negatively regulated by Shh signaling.
AB  - Limb skeletal pattern relies heavily on graded Sonic hedgehog (Shh) signaling. As
      a morphogen and growth cue, Shh regulates identities of posterior limb elements,
      including the ulna/fibula and digits 2 through 5. In contrast, proximal and
      anterior structures, including the humerus/femur, radius/tibia, and digit 1, are
      regarded as Shh independent, and mechanisms governing their specification are
      unclear. Here, we show that patterning of the proximal and anterior limb skeleton
      involves two phases. Irx3 and Irx5 (Irx3/5) are essential in the initiating limb
      bud to specify progenitors of the femur, tibia, and digit 1. However, these
      skeletal elements can be restored in Irx3/5 null mice when Shh signaling is
      diminished, indicating that Shh negatively regulates their formation after
      initiation. Our data provide genetic evidence supporting the concept of early
      specification and progressive determination of anterior limb pattern. 

PMID- 24726283
TI  - A switch from low to high Shh activity regulates establishment of limb
      progenitors and signaling centers.
AB  - The patterning and growth of the embryonic vertebrate limb is dependent on Sonic
      hedgehog (Shh), a morphogen that regulates the activity of Gli transcription
      factors. However, Shh expression is not observed during the first 12 hr of limb
      development. During this phase, the limb bud is prepatterned into anterior and
      posterior regions through the antagonistic actions of transcription factors Gli3
      and Hand2. We demonstrate that precocious activation of Shh signaling during this
      early phase interferes with the Gli3-dependent specification of anterior
      progenitors, disturbing establishment of signaling centers and normal outgrowth
      of the limb. Our findings illustrate that limb development requires a sweet spot
      in the level and timing of pathway activation that allows for the Shh-dependent
      expansion of posterior progenitors without interfering with early prepatterning
      functions of Gli3/Gli3R or specification of anterior progenitors.

PMID- 24726284
TI  - Silymarin improved 6-OHDA-induced motor impairment in hemi-parkisonian rats:
      behavioral and molecular study.
AB  - BACKGROUND: Neuroinflammation and oxidative stress has been shown to be
      associated with the development of Parkinson disease (PD). In the present study,
      we investigated the effect of intraperitoneal (i.p.) administration of silymarin,
      on 6-OHDA-induced motor-impairment, brain lipid per-oxidation and cerebrospinal
      fluid (CSF) levels of inflammatory cytokine in the rats. RESULTS: The results
      showed that silymarin is able to improve motor coordination significantly (p <
      0.001) in a dose dependent manner. There was a significant (p < 0.001) increase
      in MDA levels of 6-OHDA-lesioned rats whereas; in silymarin (100, 200 and 300
      mg/kg, i.p. for 5 days) pre-treated hemi-parkinsonian rats MDA levels was
      decreased markedly (p < 0.001). Furthermore the CSF levels of IL-1beta was
      decreased (p < 0.001) in silymarin (100, 200 and 300 mg/kg) pre-treated rats up
      to the range of normal non-parkinsonian animals. CONCLUSION: We found that pre
      treatment with silymarin could improve 6-OHDA-induced motor imbalance by
      attenuating brain lipid per-oxidation as well as CSF level of IL-1beta as a pro
      inflammatory cytokine. We suggest a potential prophylactic effect for silymarin
      in PD. However, further clinical trial studies should be carried out to prove
      this hypothesis.

PMID- 24726285
TI  - Comparing memory and meta-memory abilities between children with acquired brain
      injury and healthy peers.
AB  - This study compared visual memory and meta-memory abilities of children with ABI
      to that of healthy peers. Participants included 16 children (aged 13.55 +/- 3.29
      years) with moderate or severe ABI and 16 healthy children (aged 12.44 +/- 3.24
      years) with typical development. Children completed the Contextual Memory Test
      for Children (CMT-CH). The study group showed significantly lower immediate and
      delayed recall abilities. While the controls used the context for better
      memorizing, most of the children with ABI used rehearsals. In both groups better
      delayed recall correlated with the use of a more efficient strategy. Meta-memory
      should be an integral part of the assessment for children with ABI. Therapists
      should enhance child's self-awareness to his/her abilities and encourage the use
      of strategies (e.g. context) for memorizing in daily life.

PMID- 24726286
TI  - Phase 1 pharmacogenetic and pharmacodynamic study of sorafenib with concurrent
      radiation therapy and gemcitabine in locally advanced unresectable pancreatic
      cancer.
AB  - PURPOSE: To define the safety, efficacy, and pharmacogenetic and pharmacodynamic
      effects of sorafenib with gemcitabine-based chemoradiotherapy (CRT) in locally
      advanced pancreatic cancer. METHODS AND MATERIALS: Patients received gemcitabine
      1000 mg/m(2) intravenously weekly * 3 every 4 weeks per cycle for 1 cycle before
      CRT and continued for up to 4 cycles after CRT. Weekly gemcitabine 600 mg/m(2)
      intravenously was given during concurrent intensity modulated radiation therapy
      of 50 Gy to gross tumor volume in 25 fractions. Sorafenib was dosed orally 400 mg
      twice daily until progression, except during CRT when it was escalated from 200
      mg to 400 mg daily, and 400 mg twice daily. The maximum tolerated dose cohort was
      expanded to 15 patients. Correlative studies included dynamic contrast-enhanced
      MRI and angiogenesis genes polymorphisms (VEGF-A and VEGF-R2 single nucleotide
      polymorphisms). RESULTS: Twenty-seven patients were enrolled. No dose-limiting
      toxicity occurred during induction gemcitabine/sorafenib followed by concurrent
      CRT. The most common grade 3/4 toxicities were fatigue, hematologic, and
      gastrointestinal. The maximum tolerated dose was sorafenib 400 mg twice daily.
      The median progression-free survival and overall survival for 25 evaluable
      patients were 10.6 and 12.6 months, respectively. The median overall survival for
      patients with VEGF-A -2578 AA, -1498 CC, and -1154 AA versus alternate genotypes
      was 21.6 versus 14.7 months. Dynamic contrast-enhanced MRI demonstrated higher
      baseline K(trans) in responding patients. CONCLUSIONS: Concurrent sorafenib with
      CRT had modest clinical activity with increased gastrointestinal toxicity in
      localized unresectable pancreatic cancer. Select VEGF-A/VEGF-R2 genotypes were
      associated with favorable survival.

PMID- 24726287
TI  - A prospective study of 18FDG-PET with CT coregistration for radiation treatment
      planning of lymphomas and other hematologic malignancies.
AB  - PURPOSE: This prospective single-institution study examined the impact of
      positron emission tomography (PET) with the use of 2-[(18)F] fluoro-2
      deoxyglucose and computed tomography (CT) scan radiation treatment planning (TP)
      on target volume definition in lymphoma. METHODS AND MATERIALS: 118 patients
      underwent PET/CT TP during June 2007 to May 2009. Gross tumor volume (GTV) was
      contoured on CT-only and PET/CT studies by radiation oncologists (ROs) and
      nuclear medicine physicians (NMPs) for 95 patients with positive PET scans.
      Treatment plans and dose-volume histograms were generated for CT-only and PET/CT
      for 95 evaluable sites. Paired t test statistics and Pearson correlation
      coefficients were used for analysis. RESULTS: 70 (74%) patients had non-Hodgkin
      lymphoma, 10 (11%) had Hodgkin lymphoma, 12 (10%) had plasma-cell neoplasm, and 3
      (3%) had other hematologic malignancies. Forty-three (45%) presented with
      relapsed/refractory disease. Forty-five (47%) received no prior chemotherapy. The
      addition of PET increased GTV as defined by ROs in 38 patients (median, 27%;
      range, 5%-70%) and decreased GTV in 41 (median, 39.5%; range, 5%-80%). The
      addition of PET increased GTV as defined by NMPs in 27 patients (median, 26.5%;
      range, 5%-95%) and decreased GTV in 52 (median, 70%; range, 5%-99%). The
      intraobserver correlation between CT-GTV and PET-GTV was higher for ROs than for
      NMPs (0.94, P<.01 vs 0.89, P<.01). On the basis of Bland-Altman plots, the PET
      GTVs defined by ROs were larger than those defined by NMPs. On evaluation of
      clinical TPs, only 4 (4%) patients had inadequate target coverage (D95 <95%) of
      the PET-GTV defined by NMPs. CONCLUSIONS: Significant differences between the RO
      and NMP volumes were identified when PET was coregistered to CT for radiation
      planning. Despite this, the PET-GTV defined by ROs and NMPs received acceptable
      prescription dose in nearly all patients. However, given the potential for a
      marginal miss, consultation with an experienced PET reader is highly encouraged
      when PET/CT volumes are delineated, particularly for questionable lesions and to
      assure complete and accurate target volume coverage.

PMID- 24726288
TI  - Single-fraction proton beam stereotactic radiosurgery for cerebral arteriovenous
      malformations.
AB  - PURPOSE/OBJECTIVE(S): To evaluate the obliteration rate and potential adverse
      effects of single-fraction proton beam stereotactic radiosurgery (PSRS) in
      patients with cerebral arteriovenous malformations (AVMs). METHODS AND MATERIALS:
      From 1991 to 2010, 248 consecutive patients with 254 cerebral AVMs received
      single-fraction PSRS at our institution. The median AVM nidus volume was 3.5 cc
      (range, 0.1-28.1 cc), 23% of AVMs were in critical/deep locations (basal ganglia,
      thalamus, or brainstem), and the most common prescription dose was 15 Gy(relative
      biological effectiveness [RBE]). Univariable and multivariable analyses were
      performed to assess factors associated with obliteration and hemorrhage. RESULTS:
      At a median follow-up time of 35 months (range, 6-198 months), 64.6% of AVMs were
      obliterated. The median time to total obliteration was 31 months (range, 6-127
      months), and the 5-year and 10-year cumulative incidence of total obliteration
      was 70% and 91%, respectively. On univariable analysis, smaller target volume
      (hazard ratio [HR] 0.78, 95% confidence interval [CI] 0.86-0.93, P<.0001),
      smaller treatment volume (HR 0.93, 95% CI 0.90-0.96, P<.0001), higher
      prescription dose (HR 1.16, 95% CI 1.07-1.26, P=.001), and higher maximum dose
      (HR 1.14, 95% CI 1.05-1.23, P=.002) were associated with total obliteration.
      Deep/critical location was also associated with decreased likelihood of
      obliteration (HR 0.68, 95% CI 0.47-0.98, P=.04). On multivariable analysis,
      critical location (adjusted HR [AHR] 0.42, 95% CI 0.27-0.65, P<.001) and smaller
      target volume (AHR 0.81, 95% CI 0.68-0.97, P=.02) remained associated with total
      obliteration. Posttreatment hemorrhage occurred in 13 cases (5-year cumulative
      incidence of 7%), all among patients with less than total obliteration, and 3 of
      these events were fatal. The most common complication was seizure, controlled
      with medications, both acutely (8%) and in the long term (9.1%). CONCLUSIONS: The
      current series is the largest modern series of PSRS for cerebral AVMs. PSRS can
      achieve a high obliteration rate with minimal morbidity. Post-treatment
      hemorrhage remains a potentially fatal risk among patients who have not yet
      responded to treatment.

PMID- 24726289
TI  - Quantification of proton dose calculation accuracy in the lung.
AB  - PURPOSE: To quantify the accuracy of a clinical proton treatment planning system
      (TPS) as well as Monte Carlo (MC)-based dose calculation through measurements and
      to assess the clinical impact in a cohort of patients with tumors located in the
      lung. METHODS AND MATERIALS: A lung phantom and ion chamber array were used to
      measure the dose to a plane through a tumor embedded in the lung, and to
      determine the distal fall-off of the proton beam. Results were compared with TPS
      and MC calculations. Dose distributions in 19 patients (54 fields total) were
      simulated using MC and compared to the TPS algorithm. RESULTS: MC increased dose
      calculation accuracy in lung tissue compared with the TPS and reproduced dose
      measurements in the target to within +/-2%. The average difference between
      measured and predicted dose in a plane through the center of the target was 5.6%
      for the TPS and 1.6% for MC. MC recalculations in patients showed a mean dose to
      the clinical target volume on average 3.4% lower than the TPS, exceeding 5% for
      small fields. For large tumors, MC also predicted consistently higher V5 and V10
      to the normal lung, because of a wider lateral penumbra, which was also observed
      experimentally. Critical structures located distal to the target could show large
      deviations, although this effect was highly patient specific. Range measurements
      showed that MC can reduce range uncertainty by a factor of ~2: the average
      (maximum) difference to the measured range was 3.9 mm (7.5 mm) for MC and 7 mm
      (17 mm) for the TPS in lung tissue. CONCLUSION: Integration of Monte Carlo dose
      calculation techniques into the clinic would improve treatment quality in proton
      therapy for lung cancer by avoiding systematic overestimation of target dose and
      underestimation of dose to normal lung. In addition, the ability to confidently
      reduce range margins would benefit all patients by potentially lowering toxicity.

PMID- 24726290
TI  - The impact of variations in a fact-based front-of-package nutrition labeling
      system on consumer comprehension.

PMID- 24726291
TI  - Down-regulation of FoxM1 leads to the inhibition of the epithelial-mesenchymal
      transition in gastric cancer cells.
AB  - Emerging evidence suggests that FoxM1 may have a crucial role in the development
      and progression of human gastric cancer. Therefore, we sought to determine the
      role of FoxM1 in gastric cancer epithelial-mesenchymal transition (EMT). The down
      regulation of FoxM1 expression by the transfection of cells with FoxM1 siRNA
      decreased cell migration, invasion, and proliferation. Moreover, the over
      expression of FoxM1 promoted cell migration, invasion, and proliferation, which
      led to the acquisition of an EMT phenotype by up-regulating the protein
      expression of the mesenchymal cell markers ZEB1, ZEB2, and vimentin and by down
      regulating the epithelial cell marker E-cadherin in gastric epithelial cells.
      More important, the depletion of FoxM1 levels in gastric cancer cells led to
      significant decreases in the NF-kappaB p65 subunit, cyclin D1, Hes-1, VEGF, and
      EpCAM protein levels. Real-time PCR examination showed that the down-regulation
      of FoxM1 expression significantly inhibited vimentin and N-cadherin expression
      compared to that in control cells. Most important, cells transfected with FoxM1
      siRNA displayed an elongated/irregular fibroblastoid morphology and reduction of
      the vimentin expression. Our current study strongly suggests that FoxM1 signaling
      has important roles in tumor cell aggressiveness through the acquisition of the
      EMT phenotype in gastric cancer cells. 

PMID- 24726293
TI  - Reprint of: Heparan sulfate as a regulator of endochondral ossification and
      osteochondroma development.
AB  - Most elements of the vertebrate skeleton are formed by endochondral ossification.
      This process is initiated with mesenchymal cells that condense and differentiate
      into chondrocytes. These undergo several steps of differentiation from
      proliferating into hypertrophic chondrocytes, which are subsequently replaced by
      bone. Chondrocyte proliferation and differentiation are tightly controlled by a
      complex network of signaling molecules. During recent years, it has become
      increasingly clear that heparan sulfate (HS) carrying proteoglycans play a
      critical role in controlling the distribution and activity of these secreted
      factors. In this review we summarize the current understanding of the role of HS
      in regulating bone formation. In human, mutations in the HS synthetizing enzymes
      Ext1 and Ext2 induce the Multiple Osteochondroma syndrome, a skeletal disorder
      characterized by short stature and the formation of benign cartilage-capped
      tumors. We review the current insight into the origin of the disease and discuss
      its possible molecular basis. In addition, we summarize the existing insight into
      the role of HS as a regulator of signal propagation and signaling strength in the
      developing skeleton. 

PMID- 24726292
TI  - Reprint of: Decorin activates AMPK, an energy sensor kinase, to induce autophagy
      in endothelial cells.
AB  - The highly conserved eukaryotic process of macroautophagy (autophagy) is a non
      specific bulk-degradation program critical for maintaining proper cellular
      homeostasis, and for clearing aged and damaged organelles. This decision is
      inextricably dependent upon prevailing metabolic demands and energy requirements
      of the cell. Soluble monomeric decorin functions as a natural tumor repressor
      that antagonizes a variety of receptor tyrosine kinases. Recently, we discovered
      that decorin induces endothelial cell autophagy, downstream of VEGFR2. This
      process was wholly dependent upon Peg3, a decorin-inducible genomically imprinted
      tumor suppressor gene. However, the signaling cascades responsible have remained
      elusive. In this report we discovered that Vps34, a class III phosphoinositide
      kinase, is an upstream kinase required for Peg3 induction. Moreover, decorin
      triggered differential formation of Vps34/Beclin 1 complexes with concomitant
      dissolution of inhibitive Bcl-2/Beclin 1 complexes. Further, decorin inhibited
      anti-autophagic signaling via suppression of Akt/mTOR/p70S6K activity with the
      concurrent activation of pro-autophagic AMPK-mediated signaling cascades.
      Mechanistically, AMPK is downstream of VEGFR2 and inhibition of AMPK signaling
      abrogated decorin-evoked autophagy. Collectively, these findings hint at the
      complexity of the underlying molecular relays necessary for decorin-evoked
      endothelial cell autophagy and reveal important therapeutic targets for
      augmenting autophagy and combatting tumor angiogenesis. 

PMID- 24726294
TI  - Effect of N-acetylcysteine combined with infliximab on toxic epidermal
      necrolysis. A proof-of-concept study.
AB  - INTRODUCTION: The pathophysiology of toxic epidermal necrolysis (TEN) is thought
      to be related to a drug-induced oxidative stress combined with TNFalpha
      overexpression by keratinocytes. None of the current treatments for TEN including
      systemic corticosteroids, cyclosporine and intravenous administration of
      immunoglobulins has proven superior over supportive care only. METHODS: A total
      of 10 TEN patients were enrolled to be treated at admission in burn units with
      the antioxidant N-acetylcysteine [NAC, 150mg/kg in a 20-h intravenous (IV)
      administration], or the combination of the same IV NAC perfusion with the anti
      TNFalpha antibody infliximab (Remicade((r))), administered at a 5mg/kg dosage as
      a single 2-h IV administration. TEN was confirmed by a skin biopsy taken from a
      bullous lesion. At entry in the trial and 48h later, the illness auxiliary score
      (IAS) of clinical severity was determined and the extent in altered skin area
      (erythema and blisters) was assessed as a relative body area. Skin biopsies of
      both clinically uninvolved and erythematous areas were collected and
      immunohistochemistry was performed for assessing the density of inflammatory
      cells (CD8+ T cells, CD68+ macrophages) and keratinocytes enriched in
      intracellular calcium (Ca(++)) identified by the Mac387 anti-calprotectin
      antibody. RESULTS: No unexpected drug-induced adverse event was noticed. After
      48h of both treatment modalities, improvements were not observed in the extent of
      skin involvement and in IAS. Immunohistopathology showed the absence of reduction
      in the amount of intraepidermal inflammatory cells. An increased intracellular
      Ca(++) load in clinically uninvolved keratinocytes and in erythematous epidermis
      was noticed. This latter finding suggested the progression in the way of the
      apoptotic process. On burn unit discharge, the survival in each modality of
      treatment was not improved compared to the expected outcomes determined from the
      IAS at admission. CONCLUSIONS: In this proof-to-concept attempt, NAC treatment or
      its combination with infliximab did not appear to reverse the evolving TEN
      process.

PMID- 24726295
TI  - Coronary and microvascular physiology during intra-aortic balloon
      counterpulsation.
AB  - OBJECTIVES: This study sought to identify the effect of coronary autoregulation
      on myocardial perfusion during intra-aortic balloon pump (IABP) therapy.
      BACKGROUND: IABP is the most commonly used circulatory support device, although
      its efficacy in certain scenarios has been questioned. The impact of alterations
      in microvascular function on IABP efficacy has not previously been evaluated in
      humans. METHODS: Thirteen patients with ischemic cardiomyopathy (left ventricular
      ejection fraction: 34 +/- 8%) undergoing percutaneous coronary intervention were
      recruited. Simultaneous intracoronary pressure and Doppler-flow measurements were
      undertaken in the target vessel following percutaneous coronary intervention,
      during unassisted and IABP-assisted conditions. Coronary autoregulation was
      modulated by the use of intracoronary adenosine, inducing maximal hyperemia. Wave
      intensity analysis characterized the coronary wave energies associated with
      balloon counterpulsation. RESULTS: Two unique diastolic coronary waves were
      temporally associated with IABP device use; a forward compression wave and a
      forward expansion wave caused by inflation and deflation, respectively. During
      basal conditions, IABP therapy increased distal coronary pressure (82.4 +/- 16.1
      vs. 88.7 +/- 17.8 mm Hg, p = 0.03), as well as microvascular resistance (2.32 +/-
      0.52 vs. 3.27 +/- 0.41 mm Hg cm s(-1), p = 0.001), with no change in average peak
      velocity (30.6 +/- 12.0 vs. 26.6 +/- 11.3 cm s(-1), p = 0.59). When
      autoregulation was disabled, counterpulsation caused an increase in average peak
      velocity (39.4 +/- 10.5 vs. 44.7 +/- 17.5 cm s(-1), p = 0.002) that was linearly
      related with IABP-forward compression wave energy (R(2) = 0.71, p = 0.001).
      CONCLUSIONS: Autoregulation ameliorates the effect of IABP on coronary flow.
      However, during hyperemia, IABP augments myocardial perfusion, principally due to
      a diastolic forward compression wave caused by balloon inflation, suggesting IABP
      would be of greatest benefit when microcirculatory reserve is exhausted.

PMID- 24726296
TI  - Pregnancy and delivery in women with Pompe disease.
AB  - BACKGROUND: The obstetric risk in patients with Pompe disease (glycogen storage
      disease type II), a mainly skeletal muscle disorder, is unknown. METHODS: The
      clinical course and the outcome of pregnancy, and the effect of pregnancy on
      disease manifestations or clinical signs and symptoms in Pompe disease were
      analyzed retrospectively using a questionnaire. Participating women with Pompe
      disease were recruited by the German and the UK sections of the International
      Pompe Association, and by centers associated within the German Pompe Group. The
      data was compared with information from the German statistical almanac, perinatal
      registry, and perinatal quality survey. RESULTS: 66 of 136 women responded to the
      questionnaire (median age: 47 years, range: 18-74). In 10 of 52 women who had
      been pregnant, the symptoms of Pompe disease were present during pregnancy (n=7
      1st, n=1 2nd, n=1 3rd pregnancy). Muscle weakness worsened in 3 women, and first
      presented in 3 others during the first pregnancy (4.5% each). Respiratory
      problems deteriorated in 2/10 women during pregnancy. These 10 symptomatic women
      had 17 pregnancies (15 deliveries, 2 miscarriages, no abortions). The 42
      asymptomatic women (63.6%) had 109 pregnancies (72.4% deliveries, 19.3%
      miscarriages, 7.3% abortions). There were no significant differences between the
      mean duration of pregnancies or the mean birth weight in symptomatic and
      asymptomatic women, or compared to the data from the general population. The same
      was true of pregnancy and delivery complications (including Cesarean section).
      CONCLUSIONS: Our data show that women with Pompe disease do not appear to have an
      increased risk of pregnancy or delivery complications. However, muscle weakness
      and respiratory complications might manifest or worsen during pregnancy in some
      women.

PMID- 24726297
TI  - Response to the letter by Drs. Van der Steen and Arcand.

PMID- 24726298
TI  - Ultra-weak photon emission from biological samples: definition, mechanisms,
      properties, detection and applications.
AB  - This review attempts to summarize molecular mechanisms, spectral and intensity
      properties, detection techniques and applications of ultra-weak photon emission.
      Ultra-weak photon emission is the chemiluminescence from biological systems where
      electronically excited species are formed during oxidative metabolic or oxidative
      stress processes. It is generally accepted that photons are emitted (1) at near
      UVA, visible, and near IR spectral ranges from 350 to 1300nm and (2) at the
      intensity of photon emission in the range of several units to several hundreds
      (oxidative metabolic process) and several hundreds to several thousands
      (oxidative stress process) photons s(-1)cm(-2). Current development in detection
      using low-noise photomultiplier tubes and imaging using highly sensitive charge
      coupled device cameras allows temporal and spatial visualization of oxidative
      metabolic or oxidative stress processes, respectively. As the phenomenon of ultra
      weak photon emission reflects oxidative metabolic or oxidative stress processes,
      it can be widely used as a non-invasive tool for monitoring of the physiological
      state of biological systems. 

PMID- 24726299
TI  - Factors and trade-offs with rehabilitation effectiveness and efficiency in newly
      disabled older persons.
AB  - OBJECTIVE: To determine the factors for rehabilitation effectiveness (REs) and
      rehabilitation efficiency (REy) among newly disabled older persons and if there
      is any trade-off between REs and REy. DESIGN: Retrospective cohort study.
      SETTING: Rehabilitation hospitals. PARTICIPANTS: Patients (N=8828) aged >=65
      years admitted for inpatient rehabilitation from 1996 to 2005. INTERVENTIONS: Not
      applicable. MAIN OUTCOME MEASURES: Independent factors affecting REs and REy were
      determined. The median rank ratios of REs to REy for each admission Barthel Index
      (BI) unit and number of days of stay were generated. The ideal ranges of
      admission BI score and length of stay (LOS) that corresponded to the REs to REy
      median rank ratio of 1 (both REs and REy optimized) were identified. RESULTS:
      Factors associated with poorer REs and REy were older age, Malay ethnicity,
      delayed admission, admission diagnosis of amputation, and comorbidities of
      dementia and stroke. An increase of 10 in admission BI score was associated with
      an increase of 3.47% in REs but a decrease of 1.1 per 30 days in REy; and an
      increase in LOS of 2.7 days was associated with an increase of 28% in REs but a
      decrease of 5.2 per 30 days in REy. A trade-off relation between REs and REy with
      respect to admission functional status and LOS was observed. The range, which
      optimized both REs and REy, was 50 to 59 units for admission BI score and 37 to
      46 days for LOS. CONCLUSIONS: There are trade-offs between REs and REy with
      respect to admission functional status and LOS. Clinicians, policymakers,
      patients, and other stakeholders should be aware of such trade-offs when they
      make joint policy decisions about rehabilitation services.

PMID- 24726301
TI  - Extended duration local anesthetic agent in a rat paw model.
AB  - Encapsulated local anesthetics extend postoperative analgesic effect following
      site-directed nerve injection; potentially reducing postoperative complications.
      Our study aim was to investigate efficacy of our improved extended duration
      formulation - 15% bupivacaine in poly(DL-lactic acid co castor oil) 3:7
      synthesized by ring opening polymerization. In vitro, around 70% of bupivacaine
      was released from the p(DLLA-CO) 3:7 after 10 days. A single injection of the
      optimal formulation of 15% bupivacaine-polymer or plain (0.5%) bupivacaine
      (control), was injected via a 22G needle beside the sciatic nerve of Sprague
      Dawley rats under anesthesia; followed (in some animals) by a 1cm longitudinal
      incision through the skin and fascia of the paw area. Behavioral tests for
      sensory and motor block assessment were done using Hargreave's hot plate score,
      von Frey filaments and rearing count. The 15% bupivacaine formulation
      significantly prolonged sensory block duration up to at least 48 h. Following
      surgery, motor block was observed for 48 h following administration of
      bupivacaine-polymer formulation and rearing was reduced (returning to baseline
      after 48 h). No significant differences in mechanical nociceptive response were
      observed. The optimized bupivacaine-polymer formulation prolonged duration of
      local anesthesia effect in our animal model up to at least 48 h.

PMID- 24726300
TI  - Preliminary pharmaceutical development of antimalarial-antibiotic cotherapy as a
      pre-referral paediatric treatment of fever in malaria endemic areas.
AB  - Artemether (AM) plus azithromycin (AZ) rectal co-formulations were studied to
      provide pre-referral treatment for children with severe febrile illnesses in
      malaria-endemic areas. The target profile required that such product should be
      cheap, easy to administer by non-medically qualified persons, rapidly effective
      against both malaria and bacterial infections. Analytical and pharmacotechnical
      development, followed by in vitro and in vivo evaluation, were conducted for
      various AMAZ coformulations. Of the formulations tested, stability was highest
      for dry solid forms and bioavailability for hard gelatin capsules; AM release
      from AMAZ rectodispersible tablet was suboptimal due to a modification of its
      micro-crystalline structure. 

PMID- 24726302
TI  - Interactions of cyclic and non-cyclic naphthalene diimide derivatives with
      different nucleic acids.
AB  - Recently, strategy based on stabilization of G-quadruplex telomeric DNA by small
      organic molecule has been realized by naphthalene diimide derivatives (NDIs). At
      the same time NDIs bind to DNA duplex as threading intercalators. Here we present
      cyclic derivative of naphthalene diimide (ligand 1) as DNA-binding ligand with
      ability to recognition of different structures of telomeric G-quadruplexes and
      ability to bis-intercalate to double-stranded helixes. The results have been
      compared to non-cyclic derivative (ligand 2) and revealed that preferential
      binding of ligands to nucleic acids strongly depends on their topology and
      structural features of ligands. 

PMID- 24726303
TI  - Detection of cyclin D1 mRNA by hybridization sensitive NIC-oligonucleotide probe.
AB  - A large group of fluorescent hybridization probes, includes intercalating dyes
      for example thiazole orange (TO). Usually TO is coupled to nucleic acids post
      synthetically which severely limits its use. Here, we have developed a
      phosphoramidite monomer, 10, and prepared a 2'-OMe-RNA probe, labeled with 5
      (trans-N-hexen-1-yl-)-TO-2'-deoxy-uridine nucleoside, dU(TO), (Nucleoside bearing
      an Inter-Calating moiety, NIC), for selective mRNA detection. We investigated a
      series of 15-mer 2'-OMe-RNA probes, targeting the cyclin D1 mRNA, containing one
      or several dU(TO) at various positions. dU(TO)-2'-OMe-RNA exhibited up to 7-fold
      enhancement of TO emission intensity upon hybridization with the complementary
      RNA versus that of the oligomer alone. This NIC-probe was applied for the
      specific detection of a very small amount of a breast cancer marker, cyclin D1
      mRNA, in total RNA extract from cancerous cells (250 ng/MUl). Furthermore, this
      NIC-probe was found to be superior to our related NIF (Nucleoside with Intrinsic
      Fluorescence)-probe which could detect cyclin D1 mRNA target only at high
      concentrations (1840 ng/MUl). Additionally, dU(T) can be used as a monomer in
      solid-phase oligonucleotide synthesis, thus avoiding the need for post-synthetic
      modification of oligonucleotide probes. Hence, we propose dU(TO)
      oligonucleotides, as hybridization probes for the detection of specific RNA in
      homogeneous solutions and for the diagnosis of breast cancer.

PMID- 24726304
TI  - Design, synthesis and evaluation of novel 2,5,6-trisubstituted benzimidazoles
      targeting FtsZ as antitubercular agents.
AB  - Filamenting temperature-sensitive protein Z (FtsZ), an essential cell division
      protein, is a promising target for the drug discovery of new-generation
      antibacterial agents against various bacterial pathogens. As a part of SAR
      studies on benzimidazoles, we have synthesized a library of 376 novel 2,5,6
      trisubstituted benzimidazoles, bearing ether or thioether linkage at the 6
      position. In a preliminary HTP screening against Mtb H37Rv, 108 compounds were
      identified as hits at a cut off concentration of 5 MUg/mL. Among those hits, 10
      compounds exhibited MIC values in the range of 0.63-12.5 MUg/mL. Light scattering
      assay and TEM analysis with the most potent compound 5a clearly indicate that its
      molecular target is Mtb-FtsZ. Also, the Kd of 5a with Mtb-FtsZ was determined to
      be 1.32 MUM.

PMID- 24726305
TI  - Preliminary investigations into triazole derived androgen receptor antagonists.
AB  - A range of 1,4-substituted-1,2,3-N-phenyltriazoles were synthesized and evaluated
      as non-steroidal androgen receptor (AR) antagonists. The motivation for this
      study was to replace the N-phenyl amide portion of small molecule antiandrogens
      with a 1,2,3-triazole and determine effects, if any, on biological activity. The
      synthetic methodology presented herein is robust, high yielding and extremely
      rapid. Using this methodology a series of 17 N-aryl triazoles were synthesized
      from commercially available starting materials in less than 3h. After preliminary
      biological screening at 20 and 40 MUM, the most promising three compounds were
      found to display IC50 values of 40-50 MUM against androgen dependent (LNCaP)
      cells and serve as a starting point for further structure-activity
      investigations. All compounds in this work were the focus of an in silico study
      to dock the compounds into the human androgen receptor ligand binding domain
      (hARLBD) and compare their predicted binding affinity with known antiandrogens. A
      comparison of receptor-ligand interactions for the wild type and T877A mutant AR
      revealed two novel polar interactions. One with Q738 of the wild type site and
      the second with the mutated A877 residue.

PMID- 24726306
TI  - Geranyl and neryl triazole bisphosphonates as inhibitors of geranylgeranyl
      diphosphate synthase.
AB  - When inhibitors of enzymes that utilize isoprenoid pyrophosphates are based on
      the natural substrates, a significant challenge can be to achieve selective
      inhibition of a specific enzyme. One element in the design process is the
      stereochemistry of the isoprenoid olefins. We recently reported preparation of a
      series of isoprenoid triazoles as potential inhibitors of geranylgeranyl
      transferase II but these compounds were obtained as a mixture of olefin isomers.
      We now have accomplished the stereoselective synthesis of these triazoles through
      the use of epoxy azides for the cycloaddition reaction followed by regeneration
      of the desired olefin. Both geranyl and neryl derivatives have been prepared as
      single olefin isomers through parallel reaction sequences. The products were
      assayed against multiple enzymes as well as in cell culture studies and
      surprisingly a Z-olefin isomer was found to be a potent and selective inhibitor
      of geranylgeranyl diphosphate synthase. 

PMID- 24726307
TI  - nNOS inhibition during profound asphyxia reduces seizure burden and improves
      survival of striatal phenotypic neurons in preterm fetal sheep.
AB  - Basal ganglia injury after hypoxia-ischemia remains common in preterm infants,
      and is closely associated with later cerebral palsy. In the present study we
      tested the hypothesis that a highly selective neuronal nitric oxide synthase
      (nNOS) inhibitor, JI-10, would improve survival of striatal phenotypic neurons
      after profound asphyxia, and that the subsequent seizure burden and recovery of
      EEG are associated with neural outcome. 24 chronically instrumented preterm fetal
      sheep were randomized to either JI-10 (3 ml of 0.022 mg/ml, n = 8) or saline (n =
      8) infusion 15 min before 25 min complete umbilical cord occlusion, or saline
      plus sham-occlusion (n = 8). Umbilical cord occlusion was associated with reduced
      numbers of calbindin-28k-, GAD-, NPY-, PV-, Calretinin- and nNOS-positive
      striatal neurons (p < 0.05 vs. sham occlusion) but not ChAT-positive neurons. JI
      10 was associated with increased numbers of calbindin-28k-, GAD-, nNOS-, NPY-, PV
      , Calretinin- and ChAT-positive striatal neurons (p < 0.05 vs. saline +
      occlusion). Seizure burden was strongly associated with loss of calbindin
      positive cells (p < 0.05), greater seizure amplitude was associated with loss of
      GAD-positive cells (p < 0.05), and with more activated microglia in the white
      matter tracts (p < 0.05). There was no relationship between EEG power after 7
      days recovery and total striatal cell loss, but better survival of NPY-positive
      neurons was associated with lower EEG power. In summary, these findings suggest
      that selective nNOS inhibition during asphyxia is associated with protection of
      phenotypic striatal projection neurons and has potential to help reduce basal
      ganglia injury in some premature babies. 

PMID- 24726308
TI  - The differential antiemetic properties of GLP-1 receptor antagonist, exendin (9
      39) in Suncus murinus (house musk shrew).
AB  - The use of glucagon-like peptide-1 (7-36) amide (GLP-1) receptor agonists for the
      treatment of type 2 diabetes mellitus is commonly associated with nausea and
      vomiting. Previous studies using Suncus murinus revealed that the GLP-1 receptor
      agonist, exendin-4, induces emesis via the brainstem and/or hypothalamus. The
      present study investigated the mechanism of exendin-4-induced emesis in more
      detail. Ondansetron (1 mg/kg, s.c.) and CP-99,994 (10 mg/kg, s.c) failed to
      reduce emesis induced by exendin-4 (3 nmol, i.c.v.), suggesting that 5-HT3 and
      NK1 receptors are not involved in the mechanism. In other studies, the GLP-1
      receptor antagonist, exendin (9-39), antagonised emesis and c-Fos expression in
      the brainstem and the paraventricular hypothalamus induced by the
      chemotherapeutic drug cisplatin (30 mg/kg, i.p.; p < 0.05), but not the emesis
      induced by nicotine (5 mg/kg, s.c.; p > 0.05), or copper sulphate pentahydrate
      (120 mg/kg, p.o.; p > 0.05). GLP-1 receptors may therefore represent a potential
      target for drugs to prevent chemotherapy-induced emesis in situations where 5-HT3
      and NK1 receptor antagonists fail. 

PMID- 24726309
TI  - Lu AF21934, a positive allosteric modulator of mGlu4 receptors, reduces the
      harmaline-induced hyperactivity but not tremor in rats.
AB  - Harmaline induces tremor in animals resembling essential tremor which has been
      suggested to result from activation of the glutamatergic olivo-cerebellar
      projection. The aim of the present study was to examine the effects of systemic
      administration of Lu AF21934, a brain-penetrating positive allosteric modulator
      of the metabotropic glutamate receptor 4 (mGlu4), on the harmaline-induced tremor
      and other forms of motor activity in rats using fully automated Force Plate
      Actimeters. The influence of harmaline on the mGlu4 mRNA expression in the
      cerebellum and inferior olive was analysed by in situ hybridization. Harmaline at
      a dose of 15 mg/kg (ip) triggered tremor which was manifested by an increase in
      the power within 9-15 Hz band and in the tremor index (a difference in power
      between bands 9-15 Hz and 0-8 Hz). Harmaline induced a biphasic effect on
      mobility, initially inhibiting the exploratory locomotor activity of rats (0-30
      min after administration), followed by an increase in their basic activity. Lu
      AF21934 (0.5-5 mg/kg sc) did not influence tremor but at doses of 0.5 and 2.5
      mg/kg reversed harmaline-induced hyperactivity. MGlu4 mRNA expression was high in
      the cerebellar cortex and low in the inferior olive. Repeated harmaline (15 mg/kg
      ip once a day for 5 days] decreased mGlu4 mRNA in the cerebellum and inferior
      olive. The present study indicates that the mGlu4 stimulation counteracts
      hyperactivity induced by harmaline which suggests the involvement of cerebellar
      glutamatergic transmission in this process. In contrast, neuronal mechanisms
      involved in tremor seem to be insensitive to the stimulation of mGlu4. 

PMID- 24726310
TI  - Emphysematous pyelonephritis: multicenter clinical and therapeutic experience in
      Mexico.
AB  - OBJECTIVE: To analyze the outcomes of emphysematous pyelonephritis (EPN), the
      impact of different treatment modalities, and to determine risk factors
      associated with mortality. METHODS: We retrospectively reviewed cases of EPN from
      3 tertiary care institutions in Mexico. The diagnosis was confirmed with computed
      tomographic scan. Treatment was classified as follows: medical management (MM),
      minimally invasive, and surgical. Demographic, clinical, biochemical, and
      radiological characteristics were assessed and compared between survivors and
      nonsurvivors. Comparison was assessed using 1-way analysis of variance and chi
      square. Univariate and multivariate logistic regression analyses were performed
      to determine prognostic factors. Main end point was mortality. RESULTS: A total
      of 62 patients were included (49 women and 13 men), with a mean age of 53.9
      years. The most common comorbidities were diabetes (69.3%) and hypertension
      (40.3%). Escherichia coli was the most common isolated microorganism (62.7%). MM
      was provided to 24.2%, minimally invasive treatment to 51.6%, open drainage to
      19.3%, and emergency nephrectomy to 4.8%. Overall mortality was 14.5% and was
      similar among different treatment modalities (P=.06). Survivors were younger
      (P=.004), had lower creatinine (P=.002), and better estimated glomerular
      filtration rate (P=.007). In univariate analysis, age (P=.009), creatinine
      (P=.009), and need for nephrectomy (P=.03) were associated with mortality. In
      multivariate logistic regression analysis, creatinine (odds ratio 1.56, 95%
      confidence interval 1.03-2.35, P=.03) and nephrectomy (odds ratio 9.7, 95%
      confidence interval 1.007-93.51, P=.049) remained significant predictors of
      mortality. CONCLUSION: EPN needs an aggressive MM and stepwise approach;
      nephrectomy should be the last resort of treatment. Creatinine level and need for
      nephrectomy are the strongest predictors of mortality according our analysis.

PMID- 24726311
TI  - Impact of low testosterone on response to treatment with tadalafil 5 mg once
      daily for erectile dysfunction.
AB  - OBJECTIVE: To evaluate, posthoc, the relationship between serum total
      testosterone and response to therapy in a study of tadalafil once daily for
      erectile dysfunction (ED). METHODS: Men were aged >=18 years, with >=3-month
      history of ED and partial prior response to on-demand (PRN) phosphodiesterase
      type 5 inhibitor (PDE5I) therapy. A 4-week maximum-dose PRN PDE5I run-in was
      followed by a 4-week nondrug washout period, then randomization to tadalafil 2.5
      mg titrated to 5 mg or tadalafil 5 mg (pooled for analyses) or placebo once daily
      for 12 weeks. Analyses compared endpoint efficacy results between low- (<300
      ng/dL) vs normal-testosterone (>=300 ng/dL) level subgroups. RESULTS:
      Improvements for tadalafil vs placebo were significant for the International
      Index of Erectile Function (IIEF) Erectile Function domain, Intercourse
      Satisfaction domain, Overall Satisfaction domain, and Question 15 (confidence in
      the ability to get and keep an erection; all P<.001), and for the Sexual
      Encounter Profile Questions 1-5 (all P<=.011). Analysis of covariance modeling
      identified significant treatment-by-subgroup interactions for the IIEF-Overall
      Satisfaction domain and erection confidence question and Sexual Encounter Profile
      Question 3. Comparing between tadalafil-treated testosterone subgroups, the IIEF
      Erectile Function domain scores improved significantly more in men with normal vs
      low testosterone (P=.022); no other significant differences were identified for
      either placebo or tadalafil. No significant differences in pre-existing
      conditions were observed between tadalafil and placebo within the normal- and low
      testosterone subgroups. CONCLUSION: In men with partial response to a PRN PDE5I,
      tadalafil 5 mg once daily significantly improved ED and sexual function vs
      placebo irrespective of testosterone levels.

PMID- 24726312
TI  - Editorial comment.

PMID- 24726313
TI  - Detection of bladder cancer by measuring CD44v6 expression in urine with real
      time quantitative reverse transcription polymerase chain reaction.
AB  - OBJECTIVE: To examine urinary CD44v6 total ribonucleic acid (RNA) expression in
      patients with bladder cancer using real-time quantitative reverse transcription
      polymerase chain reaction (qRT-PCR) and evaluate its potential as a novel marker
      of bladder cancer. METHODS: We used the bladder cancer cell line T24 and
      determined CD44v6 expression in cancer cells using in situ hybridization and
      immunohistochemistry. Subsequently, we obtained urine samples from 21 patients
      with bladder cancer and 25 patients without bladder cancer (controls). We
      extracted total RNA from the urine samples, measured CD44v6 total RNA expression
      in both groups using qRT-PCR, and compared the expression between groups. We also
      compared the sensitivity, specificity, and concordance rate between CD44v6 total
      RNA expression analysis by qRT-PCR and cytologic analysis, UroVysion fluorescent
      in situ hybridization, bladder tumor antigen identification, and nuclear matrix
      protein 22 measurements. RESULTS: We observed increased CD44v6 expression in
      bladder cancer cells using in situ hybridization and immunohistochemistry. CD44v6
      total RNA expression was significantly higher in the urine samples of patients
      with bladder cancer than in those of controls. We calculated the cutoff value
      from the receiver operating characteristic curve and obtained sensitivity and
      specificity values of 85.7% and 72.0%, respectively, for qRT-PCR analysis.
      CONCLUSION: Our results suggest that CD44v6 total RNA levels in urine can serve
      as a potential noninvasive biomarker of bladder cancer.

PMID- 24726314
TI  - Predicting urinary stone composition based on single-energy noncontrast computed
      tomography: the challenge of cystine.
AB  - OBJECTIVE: To study several measurements from a single-energy noncontrast
      computed tomography (NCCT) that may distinguish calcium oxalate, uric acid, and
      cystine stones. METHODS: Patients with pure urinary stones who had at least 1
      single-energy NCCT before the stone composition analysis from January 2008 to
      December 2012 were enrolled in this study. The analyzed data comprised stone
      size, volume, core Hounsfield unit (HU), periphery HU, absolute and relative HU
      differences between core and periphery, and HU density. After these measurements,
      an NCCT bone window was subjectively evaluated to study the homogeneity of each
      stone from core to periphery. The Spearman correlation test was used to determine
      the correlation between HU values and stone size and volume for each group.
      RESULTS: A total of 113 patients were found with pure urinary stones who also had
      a corresponding NCCT. There were 36, 47, and 30 patients in the calcium oxalate,
      uric acid, and cystine groups, respectively. The core HU, periphery HU, absolute
      and relative HU differences, and HU density were significantly different among
      the 3 groups (P<.001). Stone size and volume had a positive correlation with core
      and periphery HUs only for calcium oxalate and cystine stones. The subjective
      evaluation of the urinary calculi revealed a different pattern for each stone
      composition. CONCLUSION: Single-energy NCCT may predict calcium oxalate stones
      with a high degree of accuracy. There is an overlap in radiographic profiles of
      cystine and uric acid stones, making a definitive differentiation more
      challenging.

PMID- 24726315
TI  - Transperineal sector prostate biopsies: a local anesthetic outpatient technique.
AB  - OBJECTIVE: To describe our technique and determine the feasibility and
      tolerability of transperineal template prostate (TP) biopsies under local
      anesthesia (LA). METHODS: Fifty consecutive patients underwent TP biopsies under
      LA for investigation of an elevated prostate-specific antigen level or risk
      stratification as part of our active surveillance protocol. Tolerability was
      evaluated with a visual analog scale assessing probe discomfort, LA infiltration,
      and the biopsy procurement. Patients were also asked if they would have the
      procedure again, and in those who had undergone previous transrectal biopsies,
      how the TP technique compared. Pathologic data, clinical outcomes, and
      complications were recorded at 2 weeks. RESULTS: Mean age was 62.8 years
      (standard deviation [SD], 6.34 years) and the mean prostate-specific antigen
      level was 8.49 ng/mL (SD, 6.36 ng/mL). Mean prostate volume was 48.2 mL (SD, 19.4
      mL). Mean visual analog scale scores for discomfort caused by the ultrasound
      probe, LA injections, and biopsies were 3.08 (SD, 1.64), 3.29 (SD, 1.13), and
      2.88 (SD, 1.28), respectively. Thirty-four of 50 men (68%) had positive
      histology, 26 men had Gleason score<=3+4, 5 men had Gleason score>=4+3, and 3 had
      recurrent adenocarcinoma after radiotherapy. There were 2 complications: 1
      Clavien score 1 and 1 Clavien score 3a. CONCLUSION: LA TP biopsies are well
      tolerated, acceptable, and feasible when carried out within an outpatient
      setting.

PMID- 24726316
TI  - Histopathology of pineal germ cell tumors.
AB  - Germ cell tumors (GCTs) classically occur in gonads. However, they are the most
      frequent neoplasms in the pineal region. The pineal location of GCTs may be
      caused by the neoplastic transformation of a primordial germ cell that has
      mismigrated. The World Health Organization (WHO) recognizes 5 histological types
      of intracranial GCTs: germinoma and non-germinomatous tumors including embryonal
      carcinoma, yolk sac tumor, choriocarcinoma and mature or immature teratoma.
      Germinomas and teratomas are frequently encountered as pure tumors whereas the
      other types are mostly part of mixed GCTs. In this situation, the
      neuropathologist has to be able to identify each component of a GCT. When
      diagnosis is difficult, use of recent immunohistochemical markers such as
      OCT(octamer-binding transcription factor)3/4, Glypican 3, SALL(sal-like protein)4
      may be required. OCT3/4 is helpful in the diagnosis of germinomas, Glypican 3 in
      the diagnosis of yolk sac tumors and SALL4 in the diagnosis of the germ cell
      nature of an intracranial tumor. When the germ cell nature of a pineal tumor is
      doubtful, the finding of an isochromosome 12p suggests the diagnosis of GCT. The
      final pathological report should always be confronted with the clinical data,
      especially the serum or cerebrospinal fluid levels of beta-human chorionic
      gonadotropin (HCG) and alpha-fetoprotein. 

PMID- 24726317
TI  - Control of CSF-1 induced inflammation in teleost fish by a soluble form of the
      CSF-1 receptor.
AB  - The colony-stimulating factor-1 (CSF-1) is the principal regulator of the
      survival, proliferation, differentiation, and function of macrophages and their
      precursors, and has been shown to play a role in the etiology of inflammation. We
      recently identified a novel mechanism for the control of CSF-1 activity in
      teleost fish, through the production of an inhibitory soluble form of the CSF-1
      receptor (sCSF-1R). Primary goldfish kidney macrophages selectively expressed
      sCSF-1R during the senescence phase, which corresponds to a defined stage of in
      vitro culture development where inhibition of macrophage proliferation and
      apoptotic cell death are prominent. In contrast, primary macrophage cultures
      undergoing active proliferation displayed low levels of sCSF-1R expression.
      Addition of purified recombinant sCSF-1R to developing primary macrophage
      cultures leads to a dose-dependent decrease in macrophage proliferation and
      inhibits macrophage antimicrobial functions including chemotaxis, phagocytosis,
      and production of reactive oxygen intermediates. Using a goldfish in vivo model
      of self-resolving peritonitis, we found that sCSF-1R plays a role in the
      inhibition of inflammation, following an initial acute phase of antimicrobial
      responses within an inflammatory site. Soluble CSF-1R inhibits pro-inflammatory
      cytokine production, inhibits leukocyte recruitment to the inflammatory site and
      decreases ROS production in a dose-dependent manner. This sCSF-1R-dependent
      regulation of inflammation appears to be an elegant mechanism for the control of
      macrophage numbers at inflammatory sites of lower vertebrates. Overall, our
      results provide new insights into the evolutionary origins of the CSF-1 immune
      regulatory axis. 

PMID- 24726319
TI  - Combinations of genetic data in a study of neuroblastoma risk genotypes.
AB  - Analysis of combinations of genetic changes that occur exclusively in patients
      may be a supplementary strategy to the single-locus strategy used in many genetic
      studies. The genotypes of 16 SNPs within susceptibility loci for neuroblastoma
      (NB) were analyzed in a previous study. In the present study, combinations of
      these genotypes have been analyzed. The theoretical number of combinations of 3
      SNP genotypes taken from 16 SNPs is 15,120. Of these, 14,307 were found in 370
      patients and 803 controls; 12,772 combinations were common to both patients and
      controls; 1,213 were found in controls only; and 322 combinations were found in
      patients only. Among the latter, a cluster of 24 combinations was found to be
      significantly associated with NB (P < 0.00001).

PMID- 24726318
TI  - Stimulant use and HIV disease management among men in same-sex relationships.
AB  - BACKGROUND: Research conducted to date has focused primarily on identifying
      individual-level, psychological determinants of stimulant use and HIV disease
      management. The present cross-sectional study examined relationship factors as
      correlates of stimulant use and HIV disease management among men who have sex
      with men (MSM). METHODS: In total, 266 male couples completed a baseline
      assessment for a cohort study examining the role of relationship factors in HIV
      treatment. A computer-based assessment of relationship factors, self-reported
      alcohol and substance use, and self-reported anti-retroviral therapy (ART)
      adherence was administered. All HIV-positive participants also provided a blood
      sample to measure viral load. RESULTS: After controlling for demographic
      characteristics and relationship factors, men in a primary relationship with a
      stimulant-using partner had more than six-fold greater odds of reporting any
      stimulant use in the past three months. Among HIV-positive participants on ART
      (n=371), having a stimulant-using partner was independently associated with 67%
      lower odds of reporting perfect 30-day ART adherence and more than two-fold
      greater odds of displaying a detectable HIV viral load. In contrast, more partner
      level alcohol use was independently associated with greater odds of reporting
      perfect 3-day ART adherence and lower odds of displaying a detectable HIV viral
      load. CONCLUSIONS: Partner-level stimulant use is an important risk factor for
      individual-level stimulant use and difficulties with HIV disease management among
      MSM. To optimize the effectiveness of HIV treatment as prevention, clinical
      research is needed to develop couples-based interventions targeting stimulant use
      as a potential driver of detectable HIV viral load.

PMID- 24726320
TI  - Sonocatalytic and sonophotocatalytic degradation of Rhodamine 6G containing
      wastewaters.
AB  - The present work deals with degradation of aqueous solution of Rhodamine 6G (Rh
      6G) using sonocatalytic and sonophotocatalytic treatment schemes based on the use
      of cupric oxide (CuO) and titanium dioxide (TiO2) as the solid catalysts.
      Experiments have been carried out at the operating capacity of 2 L and constant
      initial pH of 12.5. The effect of catalyst loading on the sonochemical
      degradation has been investigated by varying the loading over the range of 1.5
      4.5 g/L. It has been observed that the maximum degradation of 52.2% was obtained
      at an optimum concentration of CuO as 1.5 g/L whereas for TiO2 maximum
      degradation was observed as 51.2% at a loading of 4 g/L over similar treatment
      period. Studies with presence of radical scavengers such as methanol (CH3OH) and
      n-butanol (C4H9OH) indicated lower extents of degradation confirming the
      dominance of radical mechanism. The combined approach of ultrasound, solid
      catalyst and scavengers has also been investigated at optimum loadings to
      simulate real conditions. The optimal solid loading was used for studies
      involving oxidation using UV irradiations where 26.4% and 28.9% of degradation
      was achieved at optimal loading of CuO and TiO2, respectively. Studies using
      combination of UV and US irradiations have also been carried out using the
      optimal concentration of the catalysts. It has been observed that maximum
      degradation of 63.3% is achieved using combined US and UV with TiO2 (4 g/L) as
      the photocatalyst. Overall it can be said that the combined processes give higher
      extent of degradation as compared to the individual processes based on US or UV
      irradiations.

PMID- 24726321
TI  - Changes in the clinical features of older patients admitted from the emergency
      department.
AB  - Demographic changes and healthcare reforms may impact the profile of hospitalized
      older persons. In this study, we sought to compare the characteristics of two
      prospective cohorts recruited at a ten-year interval (1999, n=253-2009, n=355).
      They included older patients (>=75 years) admitted through the emergency
      department for at least 48 h in acute non-geriatric wards in the same university
      hospital. The exclusion criteria were patients who were admitted directly to the
      intensive care unit, who were dependent for all 6 Activities of Daily Living
      (ADL), who had recently suffered from a major stroke, or whose with a life
      expectancy of less than 3 months. Median age was higher in 2009 than in 1999 (83
      vs. 81; p=0.020), with a higher proportion of those aged 85 years and over
      (p=0.026). Patients in the 2009 cohort were less likely to live in a nursing home
      (p=0.018), more dependent for the basic ADL (p<0.001), more independent for the
      instrumental ADL (p<0.001). They were more likely to have fallen in the previous
      year (p<0.001). They took more medications (p<0.001). Their length-of-stay was
      shorter (p<0.001), but they were more likely to be discharged to a rehabilitation
      center (p<0.001). They underwent more early re-admissions (p=0.020) and similar 3
      month functional decline (p=0.614). In conclusion, within a decade, the social,
      functional and medical characteristics of older patients admitted to hospital
      have changed significantly. In view of the high consumption of in-patient
      services by this population, hospitals must adapt to these rapid changes.

PMID- 24726322
TI  - Normalizing and scaling of data to derive human response corridors from impact
      tests.
AB  - It is well known that variability is inherent in any biological experiment. Human
      cadavers (Post-Mortem Human Subjects, PMHS) are routinely used to determine
      responses to impact loading for crashworthiness applications including civilian
      (motor vehicle) and military environments. It is important to transform measured
      variables from PMHS tests (accelerations, forces and deflections) to a standard
      or reference population, termed normalization. The transformation process should
      account for inter-specimen variations with some underlying assumptions used
      during normalization. Scaling is a process by which normalized responses are
      converted from one standard to another (example, mid-size adult male to large
      male and small-size female adults, and to pediatric populations). These responses
      are used to derive corridors to assess the biofidelity of anthropomorphic test
      devices (crash dummies) used to predict injury in impact environments and design
      injury mitigating devices. This survey examines the pros and cons of different
      approaches for obtaining normalized and scaled responses and corridors used in
      biomechanical studies for over four decades. Specifically, the equal-stress equal
      velocity and impulse-momentum methods along with their variations are discussed
      in this review. Methods ranging from subjective to quasi-static loading to
      different approaches are discussed for deriving temporal mean and plus minus one
      standard deviation human corridors of time-varying fundamental responses and
      cross variables (e.g., force-deflection). The survey offers some insights into
      the potential efficacy of these approaches with examples from recent impact tests
      and concludes with recommendations for future studies. The importance of
      considering various parameters during the experimental design of human impact
      tests is stressed. 

PMID- 24726323
TI  - Molecular basis and regulation of OTULIN-LUBAC interaction.
AB  - The linear ubiquitin (Ub) chain assembly complex (LUBAC) generates Met1-linked
      "linear" Ub chains that regulate the activation of the nuclear factor kappaB
      (NFkappaB) transcription factor and other processes. We recently discovered
      OTULIN as a deubiquitinase that specifically cleaves Met1-linked polyUb. Now, we
      show that OTULIN binds via a conserved PUB-interacting motif (PIM) to the PUB
      domain of the LUBAC component HOIP. Crystal structures and nuclear magnetic
      resonance experiments reveal the molecular basis for the high-affinity
      interaction and explain why OTULIN binds the HOIP PUB domain specifically.
      Analysis of LUBAC-induced NFkappaB signaling suggests that OTULIN needs to be
      present on LUBAC in order to restrict Met1-polyUb signaling. Moreover, LUBAC
      OTULIN complex formation is regulated by OTULIN phosphorylation in the PIM.
      Phosphorylation of OTULIN prevents HOIP binding, whereas unphosphorylated OTULIN
      is part of the endogenous LUBAC complex. Our work exemplifies how coordination of
      ubiquitin assembly and disassembly activities in protein complexes regulates
      individual Ub linkage types. 

PMID- 24726324
TI  - MOV10 Is a 5' to 3' RNA helicase contributing to UPF1 mRNA target degradation by
      translocation along 3' UTRs.
AB  - RNA helicases are important regulators of gene expression that act by remodeling
      RNA secondary structures and RNA-protein interactions. Here, we demonstrate that
      MOV10 has an ATP-dependent 5' to 3' in vitro RNA unwinding activity and determine
      the RNA-binding sites of MOV10 and its helicase mutants using PAR-CLIP. We find
      that MOV10 predominantly binds to 3' UTRs upstream of regions predicted to form
      local secondary structures and provide evidence that MOV10 helicase mutants are
      impaired in their ability to translocate 5' to 3' on their mRNA targets. MOV10
      interacts with UPF1, the key component of the nonsense-mediated mRNA decay
      pathway. PAR-CLIP of UPF1 reveals that MOV10 and UPF1 bind to RNA in close
      proximity. Knockdown of MOV10 resulted in increased mRNA half-lives of MOV10
      bound as well as UPF1-regulated transcripts, suggesting that MOV10 functions in
      UPF1-mediated mRNA degradation as an RNA clearance factor to resolve structures
      and displace proteins from 3' UTRs. 

PMID- 24726325
TI  - XPF-ERCC1 acts in Unhooking DNA interstrand crosslinks in cooperation with FANCD2
      and FANCP/SLX4.
AB  - DNA interstrand crosslinks (ICLs), highly toxic lesions that covalently link the
      Watson and Crick strands of the double helix, are repaired by a complex,
      replication-coupled pathway in higher eukaryotes. The earliest DNA processing
      event in ICL repair is the incision of parental DNA on either side of the ICL
      ("unhooking"), which allows lesion bypass. Incisions depend critically on the
      Fanconi anemia pathway, whose activation involves ubiquitylation of the FANCD2
      protein. Using Xenopus egg extracts, which support replication-coupled ICL
      repair, we show that the 3' flap endonuclease XPF-ERCC1 cooperates with
      SLX4/FANCP to carry out the unhooking incisions. Efficient recruitment of XPF
      ERCC1 and SLX4 to the ICL depends on FANCD2 and its ubiquitylation. These data
      help define the molecular mechanism by which the Fanconi anemia pathway promotes
      a key event in replication-coupled ICL repair. 

PMID- 24726326
TI  - Mouse SLX4 is a tumor suppressor that stimulates the activity of the nuclease XPF
      ERCC1 in DNA crosslink repair.
AB  - SLX4 binds to three nucleases (XPF-ERCC1, MUS81-EME1, and SLX1), and its
      deficiency leads to genomic instability, sensitivity to DNA crosslinking agents,
      and Fanconi anemia. However, it is not understood how SLX4 and its associated
      nucleases act in DNA crosslink repair. Here, we uncover consequences of mouse
      Slx4 deficiency and reveal its function in DNA crosslink repair. Slx4-deficient
      mice develop epithelial cancers and have a contracted hematopoietic stem cell
      pool. The N-terminal domain of SLX4 (mini-SLX4) that only binds to XPF-ERCC1 is
      sufficient to confer resistance to DNA crosslinking agents. Recombinant mini-SLX4
      enhances XPF-ERCC1 nuclease activity up to 100-fold, directing specificity toward
      DNA forks. Mini-SLX4-XPF-ERCC1 also vigorously stimulates dual incisions around a
      DNA crosslink embedded in a synthetic replication fork, an essential step in the
      repair of this lesion. These observations define vertebrate SLX4 as a tumor
      suppressor, which activates XPF-ERCC1 nuclease specificity in DNA crosslink
      repair. 

PMID- 24726327
TI  - Binding of OTULIN to the PUB domain of HOIP controls NF-kappaB signaling.
AB  - Linear ubiquitin chains are implicated in the regulation of the NF-kappaB
      pathway, immunity, and inflammation. They are synthesized by the LUBAC complex
      containing the catalytic subunit HOIL-1-interacting protein (HOIP) and are
      disassembled by the linear ubiquitin-specific deubiquitinase OTULIN. Little is
      known about the regulation of these opposing activities. Here we demonstrate that
      HOIP and OTULIN interact and act as a bimolecular editing pair for linear
      ubiquitin signals in vivo. The HOIP PUB domain binds to the PUB interacting motif
      (PIM) of OTULIN and the chaperone VCP/p97. Structural studies revealed the basis
      of high-affinity interaction with the OTULIN PIM. The conserved Tyr56 of OTULIN
      makes critical contacts with the HOIP PUB domain, and its phosphorylation
      negatively regulates this interaction. Functionally, HOIP binding to OTULIN is
      required for the recruitment of OTULIN to the TNF receptor complex and to
      counteract HOIP-dependent activation of the NF-kappaB pathway. 

PMID- 24726329
TI  - Synchronous electrical stimulation of laryngeal muscles: an alternative for
      enhancing recovery of unilateral recurrent laryngeal nerve paralysis.
AB  - BACKGROUND: Although electrical stimulation of the larynx has been widely studied
      for treating voice disorders, its effectiveness has not been assessed under
      safety and comfortable conditions. This article describes design, theoretical
      issues, and preliminary evaluation of an innovative system for transdermal
      electrical stimulation of the larynx. The proposed design includes
      synchronization of electrical stimuli with laryngeal neuromuscular activity.
      OBJECTIVE: To study whether synchronous electrical stimulation of the larynx
      could be helpful for improving voice quality in patients with dysphonia due to
      unilateral recurrent laryngeal nerve paralysis (URLNP). MATERIALS AND METHODS: A
      3-year prospective study was carried out at the Instituto Nacional de
      Rehabilitacion in the Mexico City. Ten patients were subjected to transdermal
      current electrical stimulation synchronized with the fundamental frequency of the
      vibration of the vocal folds during phonation. The stimulation was triggered
      during the phase of maximum glottal occlusion. A complete acoustic voice analysis
      was performed before and after the period of electrical stimulation. RESULTS:
      Acoustic analysis revealed significant improvements in all parameters after the
      stimulation period. CONCLUSION: Transdermal synchronous electrical stimulation of
      vocal folds seems to be a safe and reliable procedure for enhancing voice quality
      in patients with (URLNP).

PMID- 24726328
TI  - An Rrp6-like protein positively regulates noncoding RNA levels and DNA
      methylation in Arabidopsis.
AB  - Rrp6-mediated nuclear RNA surveillance tunes eukaryotic transcriptomes through
      noncoding RNA degradation and mRNA quality control, including exosomal RNA decay
      and transcript retention triggered by defective RNA processing. It is unclear
      whether Rrp6 can positively regulate noncoding RNAs and whether RNA retention
      occurs in normal cells. Here we report that AtRRP6L1, an Arabidopsis Rrp6-like
      protein, controls RNA-directed DNA methylation through positive regulation of
      noncoding RNAs. Discovered in a forward genetic screen, AtRRP6L1 mutations
      decrease DNA methylation independently of exosomal RNA degradation. Accumulation
      of Pol V-transcribed scaffold RNAs requires AtRRP6L1 that binds to RNAs in vitro
      and in vivo. AtRRP6L1 helps retain Pol V-transcribed RNAs in chromatin to enable
      their scaffold function. In addition, AtRRP6L1 is required for genome-wide Pol IV
      dependent siRNA production that may involve retention of Pol IV transcripts. Our
      results suggest that AtRRP6L1 functions in epigenetic regulation by helping with
      the retention of noncoding RNAs in normal cells. 

PMID- 24726330
TI  - Comparative analysis of vocal fold vibration using high-speed videoendoscopy and
      digital kymography.
AB  - OBJECTIVES: To compare high-speed videoendoscopy (HSV) and digital kymography
      (DKG) in the vocal fold vibration analysis of normophonic women with no vocal
      fold abnormalities. STUDY DESIGN: Prospective study comparing quantitative
      parameters extracted by HSV and DKG. METHODS: Eighteen normophonic women whose
      age ranged from 18 to 45 years participated in the study. The procedures
      comprised HSV and DKG of the medial line of the vocal folds. The parameters
      evaluated were fundamental frequency (F0), open quotient (OQ), and duration of
      vibration cycle phases (open phase, closed phase, opening phase, and closing
      phase). RESULTS: The F0 results of HSV and DKG were similar. However, significant
      differences were found in both duration of vibration cycle phases and OQ,
      indicating a longer open phase in the vocal fold vibration when this phase was
      measured by HSV. CONCLUSIONS: The results emphasize the need to set up different
      normative threshold values for both HSV and DKG.

PMID- 24726331
TI  - Vocal fold dynamics for frequency change.
AB  - This article provides a review of data drawn from a series of related experiments
      to demonstrate how frequency change (Deltaf0) is accomplished in the modal
      register. The research cited involves studies of (1) laryngeal size, (2) vocal
      fold length, (3) vocal fold thickness, and (4) subglottic pressure; new data
      describe their effect on vocal fold mass. It was found that changes in these
      dimensions (1) explain how the shifts in frequency are accomplished, (2)
      establish the way vocal fold mass can be measured, and (3) strongly support the
      aerodynamic-myoelastic theory of phonation. 

PMID- 24726332
TI  - Management of supraglottic stenosis using a novel stent design.
AB  - OBJECTIVES: To present a novel design for a stent for management of a traumatic
      supraglottic web. METHODS: Case report and literature review (PubMed 1964-2013).
      RESULTS: A 48-year-old man was presented after penetrating laryngeal trauma. He
      had severe dysphonia and was tracheotomy dependent. He had been treated
      previously with open reduction and fixation of laryngeal fracture. On
      examination, we identified an avulsed left vocal fold and a supraglottic web. He
      initially underwent reapproximation of the avulsed left vocal fold, and
      subsequently, the supraglottic web was treated using a stent designed by the
      senior author (R.T.S.). In addition, he underwent later resection of scar tissue
      to improve dysphonia and then he was decanulated. CONCLUSIONS: There are a few
      techniques presented in the literature and mostly are adaptations of subglottic
      stenosis management techniques. Individualized treatment is needed for these
      difficult cases. We present our experience with supraglottic web treatment to
      expand the literature on this uncommon disorder.

PMID- 24726333
TI  - Asymmetric processing of durational differences - electrophysiological
      investigations in Bengali.
AB  - Duration is used contrastively in many languages to distinguish word meaning
      (e.g. in Bengali, [pata] 'leaf' vs. [pat:a] 'whereabouts'). While there is a
      large body of research on other contrasts in speech perception (e.g. vowel
      contrasts and consonantal place features), little work has been done on how
      durational information is used in speech processing. In non-linguistic studies of
      low-level processing, such as visual and non-linguistic acoustic pop-out tasks,
      an asymmetry is found where additional information is more readily detected than
      missing information. In this study, event-related potentials were recorded during
      two cross-modal auditory-visual semantic priming studies, where nonword
      mispronunciations of spoken prime words were created by changing the duration of
      a medial consonant (real word [dana] 'seed'>nonword [dan:a]). N400 amplitudes
      showed an opposite asymmetric pattern of results, where increases in consonantal
      duration were tolerated and led to priming of the visual target, but decreases in
      consonantal duration were not accepted. This asymmetrical pattern of
      acceptability is attributed to the fact that a longer consonant includes all
      essential information for the recognition of the original word with a short
      medial consonant (a possible default category) and any additional information can
      be ignored. However, when a consonant is shortened, it lacks the required
      durational information to activate the word with the original long consonant.

PMID- 24726334
TI  - Phonological markers of information structure: an fMRI study.
AB  - In this fMRI study we investigate the neural correlates of information structure
      integration during sentence comprehension in Dutch. We looked into how prosodic
      cues (pitch accents) that signal the information status of constituents to the
      listener (new information) are combined with other types of information during
      the unification process. The difficulty of unifying the prosodic cues into
      overall sentence meaning was manipulated by constructing sentences in which the
      pitch accent did (focus-accent agreement), and sentences in which the pitch
      accent did not (focus-accent disagreement) match the expectations for focus
      constituents of the sentence. In case of a mismatch, the load on unification
      processes increases. Our results show two anatomically distinct effects of focus
      accent disagreement, one located in the posterior left inferior frontal gyrus
      (LIFG, BA6/44), and one in the more anterior-ventral LIFG (BA 47/45). Our results
      confirm that information structure is taken into account during unification, and
      imply an important role for the LIFG in unification processes, in line with
      previous fMRI studies.

PMID- 24726335
TI  - Improving appropriate use of echocardiography and single-photon emission computed
      tomographic myocardial perfusion imaging: a continuous quality improvement
      initiative.
AB  - BACKGROUND: Appropriate use criteria for cardiovascular imaging have been
      published, but compliance in practice has been incomplete, with persistent high
      rates of inappropriate use. The aim of this study was to show the efficacy of a
      continuous quality improvement (CQI) initiative to favorably influence the
      appropriate use of outpatient transthoracic echocardiography and single-photon
      emission computed tomographic (SPECT) myocardial perfusion imaging (MPI) in a
      large cardiovascular practice. METHODS: In this prospective study, a multiphase
      CQI initiative was implemented, and its impact on ordering patterns for
      outpatient transthoracic echocardiography and SPECT MPI was assessed. Between
      November and December 2010, a baseline analysis of the application of appropriate
      use criteria to indications for outpatient transthoracic echocardiographic
      studies (n = 203) and SPECT MPI studies (n = 205) was performed, with studies
      categorized as "appropriate," "inappropriate," "uncertain," or "unclassified."
      The CQI initiative was then begun, with (1) clinician education, including
      didactic lectures and case-based presentations with audience participation; (2)
      system changes in ordering processes, with redesigned image ordering forms; and
      (3) peer review and feedback. A follow-up analysis was then performed between
      June and August 2012, with categorization of indications for transthoracic
      echocardiographic studies (n = 206) and SPECT MPI studies (n = 206). RESULTS: At
      baseline, 73.9% of echocardiographic studies were categorized as appropriate,
      16.7% as inappropriate, 5.9% as uncertain, and 3.4% as unclassified. Similarly,
      for SPECT MPI studies 71.7% were categorized as appropriate, 18.5% as
      inappropriate, 7.8% as uncertain, and 1.9% as unclassified. Separate analysis of
      the two most important categories, appropriate and inappropriate, demonstrated a
      significant improvement after the CQI initiative, with a 63% reduction in
      inappropriate echocardiographic studies (18.5% vs 6.9%, P = .0010) and a 46%
      reduction in inappropriate SPECT MPI studies (20.5% vs 11.1%, P = .010).
      CONCLUSIONS: This study demonstrates the effective and persistent positive impact
      of a CQI initiative to reduce inappropriate ordering of cardiovascular imaging.

PMID- 24726336
TI  - Waxholm Space atlas of the Sprague Dawley rat brain.
AB  - Three-dimensional digital brain atlases represent an important new generation of
      neuroinformatics tools for understanding complex brain anatomy, assigning
      location to experimental data, and planning of experiments. We have acquired a
      microscopic resolution isotropic MRI and DTI atlasing template for the Sprague
      Dawley rat brain with 39 MUm isotropic voxels for the MRI volume and 78 MUm
      isotropic voxels for the DTI. Building on this template, we have delineated 76
      major anatomical structures in the brain. Delineation criteria are provided for
      each structure. We have applied a spatial reference system based on internal
      brain landmarks according to the Waxholm Space standard, previously developed for
      the mouse brain, and furthermore connected this spatial reference system to the
      widely used stereotaxic coordinate system by identifying cranial sutures and
      related stereotaxic landmarks in the template using contrast given by the active
      staining technique applied to the tissue. With the release of the present
      atlasing template and anatomical delineations, we provide a new tool for spatial
      orientation analysis of neuroanatomical location, and planning and guidance of
      experimental procedures in the rat brain. The use of Waxholm Space and related
      infrastructures will connect the atlas to interoperable resources and services
      for multi-level data integration and analysis across reference spaces.

PMID- 24726337
TI  - EEG source imaging of brain states using spatiotemporal regression.
AB  - Relating measures of electroencephalography (EEG) back to the underlying sources
      is a long-standing inverse problem. Here we propose a new method to estimate the
      EEG sources of identified electrophysiological states that represent spontaneous
      activity, or are evoked by a stimulus, or caused by disease or disorder. Our
      method has the unique advantage of seamlessly integrating a statistical
      significance of the source estimate while efficiently eliminating artifacts
      (e.g., due to eye blinks, eye movements, bad electrodes). After determining the
      electrophysiological states in terms of stable topographies using established
      methods (e.g.: ICA, PCA, k-means, epoch average), we propose to estimate these
      states' time courses through spatial regression of a General Linear Model (GLM).
      These time courses are then used to find EEG sources that have a similar time
      course (using temporal regression of a second GLM). We validate our method using
      both simulated and experimental data. Simulated data allows us to assess the
      difference between source maps obtained by the proposed method and those obtained
      by applying conventional source imaging of the state topographies. Moreover, we
      use data from 7 epileptic patients (9 distinct epileptic foci localized by
      intracranial EEG) and 2 healthy subjects performing an eyes-open/eyes-closed task
      to elicit activity in the alpha frequency range. Our results indicate that the
      proposed EEG source imaging method accurately localizes the sources for each of
      the electrical brain states. Furthermore, our method is particularly suited for
      estimating the sources of EEG resting states or otherwise weak spontaneous
      activity states, a problem not adequately solved before. 

PMID- 24726338
TI  - Reduced self-referential neural response during intergroup competition predicts
      competitor harm.
AB  - Why do interactions become more hostile when social relations shift from "me
      versus you" to "us versus them"? One possibility is that acting with a group can
      reduce spontaneous self-referential processing in the moral domain and, in turn,
      facilitate competitor harm. We tested this hypothesis in an fMRI experiment in
      which (i) participants performed a competitive task once alone and once with a
      group; (ii) spontaneous self-referential processing during competition was
      indexed unobtrusively by activation in an independently localized region of the
      medial prefrontal cortex (mPFC) associated with self-reference; and (iii) we
      assessed participants' willingness to harm competitors versus teammates. As
      predicted, participants who showed reduced mPFC activation in response to
      descriptions of their own moral behaviors while competing in a group were more
      willing to harm competitors. These results suggest that intergroup competition
      (above and beyond inter-personal competition) can reduce self-referential
      processing of moral information, enabling harmful behaviors towards members of a
      competitive group. 

PMID- 24726339
TI  - Nutrition in the surgical patient.

PMID- 24726340
TI  - Differences between en bloc resection and enucleation of retroperitoneal
      sarcomas.
AB  - AIM: Today, free margin surgery is the gold-standard management for soft-tissue
      sarcoma patients and one of the most important predictors of recurrence and
      survival. To obtain optimal results, a multidisciplinary approach is necessary.
      The aim of this study was to evaluate the evolution of patients with RPS treated
      by "en bloc"surgical resection versus those treated with enucleation in the first
      surgery. METHODS: Fifty-six adult patients were divided into 2 groups. Patients
      in Group A underwent enucleation surgery, and patients in Group B underwent en
      bloc surgery. The endpoints of the study were survival time and time to
      recurrence, according to histological type and first surgical strategy. RESULTS:
      Disease-free survival was longer for en bloc surgery (P<0,05), but there was no
      difference in overall survival. When comparing the histology of patients who
      underwent enucleation surgery and en bloc resection surgery, the disease-free
      survival and overall survival rates were longer for liposarcoma. In the
      multivariate analysis, only free margins and histology of liposarcoma were
      significantly associated with a better survival. CONCLUSIONS: The surgical
      management of patients with retroperitoneal sarcoma must be very aggressive,
      often requiring multivisceral resection. Considering the disease-free survival
      and overall survival rates obtained, it is clear that it is critical to manage
      patients as early as possible by a radical en bloc surgery.

PMID- 24726341
TI  - Structural determinants for the strict monomethylation activity by trypanosoma
      brucei protein arginine methyltransferase 7.
AB  - Trypanosoma brucei protein arginine methyltransferase 7 (TbPRMT7) exclusively
      generates monomethylarginine (MMA), which directs biological consequences
      distinct from that of symmetric dimethylarginine (SDMA) and asymmetric
      dimethylarginine (ADMA). However, determinants controlling the strict
      monomethylation activity are unknown. We present the crystal structure of the
      TbPRMT7 active core in complex with S-adenosyl-L-homocysteine (AdoHcy) and a
      histone H4 peptide substrate. In the active site, residues E172, E181, and Q329
      hydrogen bond the guanidino group of the target arginine and align the terminal
      guanidino nitrogen in a position suitable for nucleophilic attack on the methyl
      group of S-adenosyl-L-methionine (AdoMet). Structural comparisons and isothermal
      titration calorimetry data suggest that the TbPRMT7 active site is narrower than
      those of protein arginine dimethyltransferases, making it unsuitable to bind MMA
      in a manner that would support a second turnover, thus abolishing the production
      of SDMA and ADMA. Our results present the structural interpretations for the
      monomethylation activity of TbPRMT7. 

PMID- 24726342
TI  - Assessment of acute bronchodilator effects from specific airway resistance
      changes in stable COPD patients.
AB  - BACKGROUND: In COPD patients, reversibility is currently evaluated from the
      changes of forced expiratory volume at 1s (DeltaFEV1) and forced vital capacity
      (DeltaFVC). By lowering peripheral airway smooth muscle tone, bronchodilators
      should decrease dynamic hyperinflation, gas trapping, and possibly dyspnea at
      rest. Hence, we hypothesize that specific airway resistance changes (DeltasRAW)
      should better characterize the acute response to bronchodilators. METHODS: On two
      days, 60 COPD patients underwent dyspnea evaluation (VAS score) and pulmonary
      function testing at baseline and one hour after placebo or 300MUg indacaterol
      administration. RESULTS: Spirographic and DeltasRAW-based criteria identified as
      responders 24 and 45 patients, respectively. DeltasRAW correlated with changes of
      intrathoracic gas volume (DeltaITGV) (r=0.61; p<0.001), residual volume (DeltaRV)
      (r=0.60; p<0.001), DeltaFVC (r=0.44; p=0.001), and DeltaVAS (r=0.73; p<0.001),
      while DeltaFEV1 correlated only with DeltaFVC (r=0.34; p=0.008). Significant
      differences in terms of DeltaITGV (p=0.002), DeltaRV (p=0.023), and DeltaVAS
      (p<0.001) occurred only if patients were stratified according to DeltasRAW.
      CONCLUSIONS: In assessing the acute functional effect of bronchodilators,
      DeltasRAW-based criterion is preferable to FEV1-FVC-based criteria, being more
      closely related to bronchodilator-induced improvements of lung mechanics and
      dyspnea at rest.

PMID- 24726343
TI  - Multipotent mesenchymal stromal cells in otorhinolaryngology.
AB  - Multipotent mesenchymal stromal cells (MSCs) are primitive cells capable of
      restoring damaged mesenchyme and with the ability to differentiate into mature
      cells of bone, cartilage, muscle, fat, nerve or fibrous tissues. MSCs are
      therefore good candidates for applications in regenerative medicine and cell
      based therapy. They regenerate through self-renewal, differentiational capacity,
      immune modulation and secretion of bioactive molecules. Authors present a review
      of MSCs applications in otorhinolaryngology. The major interest is focused on
      phonosurgery, sensorineural deafness and reconstruction of large tissue defects
      with bone, cartilage or soft tissue replacement. Current evidence of MSCs
      treatment efficacy in otorhinolaryngology is based on animal models. The true
      impact on clinical treatment will not be known until clinical studies prove
      functional outcomes in human medicine. 

PMID- 24726344
TI  - Resistance to irinotecan (CPT-11) activates epidermal growth factor
      receptor/nuclear factor kappa B and increases cellular metastasis and autophagy
      in LoVo colon cancer cells.
AB  - Chemotherapy is usually applied to treat colon cancer but leads to
      chemoresistance, and increased metastasis and invasion. The main focus of this
      study is to observe effects of resistance to irinotecan (CPT-11) on metastasis,
      invasion and autophagy in CPT-11 resistant (CPT-11-R) LoVo colon cancer cells.
      CPT-11, a topoisomerase I inhibitor and a first-line chemotherapeutic drug, is
      used to treat colon cancer. CPT-11-R cells were constructed in a step-wise
      fashion with increasing CPT-11 doses. The CPT-11-R strain had a significantly
      lower expression of Wnt/beta-catenin pathway, but induced an
      EGFR/IKKalpha/beta/NF-kappaB pathway with elevated cell cycle, metastasis and
      basal autophagy.

PMID- 24726345
TI  - Assembling evidence for identifying reservoirs of infection.
AB  - Many pathogens persist in multihost systems, making the identification of
      infection reservoirs crucial for devising effective interventions. Here, we
      present a conceptual framework for classifying patterns of incidence and
      prevalence, and review recent scientific advances that allow us to study and
      manage reservoirs simultaneously. We argue that interventions can have a crucial
      role in enriching our mechanistic understanding of how reservoirs function and
      should be embedded as quasi-experimental studies in adaptive management
      frameworks. Single approaches to the study of reservoirs are unlikely to generate
      conclusive insights whereas the formal integration of data and methodologies,
      involving interventions, pathogen genetics, and contemporary surveillance
      techniques, promises to open up new opportunities to advance understanding of
      complex multihost systems. 

PMID- 24726346
TI  - Psychophysics and the evolution of behavior.
AB  - Sensory information allows animals to interpret their environment and make
      decisions. The ways in which animals perceive and measure stimuli from the social
      and physical environment guide nearly every decision they make. Thus, sensory
      perception and associated cognitive processing have a strong impact on behavioral
      evolution. Research in this area often focuses on the unique properties of the
      sensory system of an individual species, yet certain relevant features of
      perception and cognition generally hold across taxa. One such general feature is
      the proportionally based translation of physical stimulus magnitude into
      perceived stimulus magnitude. This process has been recognized for over a
      century, but recent studies have begun to consider how a law of proportional
      psychophysics, Weber's law, exerts selective force in behavioral evolution. 

PMID- 24726347
TI  - The others: our biased perspective of eukaryotic genomes.
AB  - Understanding the origin and evolution of the eukaryotic cell and the full
      diversity of eukaryotes is relevant to many biological disciplines. However, our
      current understanding of eukaryotic genomes is extremely biased, leading to a
      skewed view of eukaryotic biology. We argue that a phylogeny-driven initiative to
      cover the full eukaryotic diversity is needed to overcome this bias. We encourage
      the community: (i) to sequence a representative of the neglected groups available
      at public culture collections, (ii) to increase our culturing efforts, and (iii)
      to embrace single cell genomics to access organisms refractory to propagation in
      culture. We hope that the community will welcome this proposal, explore the
      approaches suggested, and join efforts to sequence the full diversity of
      eukaryotes. 

PMID- 24726348
TI  - Availability of drinking water in US public school cafeterias.
AB  - This study examined the availability of free drinking water during lunchtime in
      US public schools, as required by federal legislation beginning in the 2011-2012
      school year. Data were collected by mail-back surveys in nationally
      representative samples of US public elementary, middle, and high schools from
      2009-2010 to 2011-2012. Overall, 86.4%, 87.4%, and 89.4% of students attended
      elementary, middle, and high schools, respectively, that met the drinking water
      requirement. Most students attended schools with existing cafeteria drinking
      fountains and about one fourth attended schools with water dispensers. In middle
      and high schools, respondents were asked to indicate whether drinking fountains
      were clean, and whether they were aware of any water-quality problems at the
      school. The vast majority of middle and high school students (92.6% and 90.4%,
      respectively) attended schools where the respondent perceived drinking fountains
      to be clean or very clean. Approximately one in four middle and high school
      students attended a school where the survey respondent indicated that there were
      water-quality issues affecting drinking fountains. Although most schools have
      implemented the requirement to provide free drinking water at lunchtime,
      additional work is needed to promote implementation at all schools. School
      nutrition staff at the district and school levels can play an important role in
      ensuring that schools implement the drinking water requirement, as well as
      promote education and behavior-change strategies to increase student consumption
      of water at school.

PMID- 24726349
TI  - Egg n-3 fatty acid composition modulates biomarkers of choline metabolism in free
      living lacto-ovo-vegetarian women of reproductive age.
AB  - The lacto-ovo-vegetarian (LOV) dietary regimen allows eggs, which are a rich
      source of choline. Consumption of eggs by LOV women may be especially important
      during pregnancy and lactation when demand for choline is high. The aim of this
      single blind, randomized, crossover-feeding study was to determine how near-daily
      egg consumption influenced biomarkers of choline metabolism in healthy LOV women
      of reproductive age (n=15). Because long-chain n-3 fatty acids could influence
      choline metabolism, the effect of n-3-enriched vs nonenriched eggs on choline
      metabolites was also investigated. Three 8-week dietary treatments consisting of
      six n-3-enriched eggs per week, six nonenriched eggs per week, and an egg-free
      control phase were separated by 4-week washout periods. Choline metabolites were
      quantified in fasted plasma collected before and after each treatment and
      differences in posttreatment choline metabolite concentrations were determined
      with linear mixed models. The n-3-enriched and nonenriched egg treatments
      produced different choline metabolite profiles compared with the egg-free
      control; however, response to the eggs did not differ (P>0.1). Consumption of the
      n-3-enriched egg treatment yielded higher plasma free choline (P=0.02) and
      betaine (P<0.01) (vs egg-free control) concentrations, whereas consumption of the
      nonenriched egg treatment yielded borderline higher (P=0.06) plasma
      phosphatidylcholine (vs egg-free control) levels. Neither egg treatment increased
      levels of plasma trimethylamine oxide, a gut-flora-dependent oxidative choline
      metabolite implicated as a possible risk factor for cardiovascular disease.
      Overall these data suggest that egg fatty-acid composition modulates the
      metabolic use of choline. 

PMID- 24726350
TI  - Substrate water exchange in photosystem II core complexes of the extremophilic
      red alga Cyanidioschyzon merolae.
AB  - The binding affinity of the two substrate-water molecules to the water-oxidizing
      Mn4CaO5 catalyst in photosystem II core complexes of the extremophilic red alga
      Cyanidioschyzon merolae was studied in the S2 and S3 states by the exchange of
      bound 16O-substrate against 18O-labeled water. The rate of this exchange was
      detected via the membrane-inlet mass spectrometric analysis of flash-induced
      oxygen evolution. For both redox states a fast and slow phase of water-exchange
      was resolved at the mixed labeled m/z 34 mass peak: kf=52 +/- 8s-1 and ks=1.9 +/-
      0.3s-1 in the S2 state, and kf=42 +/- 2s-1 and kslow=1.2 +/- 0.3s-1 in S3,
      respectively. Overall these exchange rates are similar to those observed
      previously with preparations of other organisms. The most remarkable finding is a
      significantly slower exchange at the fast substrate-water site in the S2 state,
      which confirms beyond doubt that both substrate-water molecules are already bound
      in the S2 state. This leads to a very small change of the affinity for both the
      fast and the slowly exchanging substrates during the S2->S3 transition.
      Implications for recent models for water-oxidation are briefly discussed.

PMID- 24726351
TI  - Endovascular management of splenic arterial aneurysms.

PMID- 24726352
TI  - In-hospital bleeding events in acute coronary syndrome patients undergoing
      percutaneous coronary intervention in the era of novel P2Y12 inhibitors: insights
      from the GReek AntiPlatelet rEgistry-GRAPE.

PMID- 24726353
TI  - Complex left atrial cor triatriatum associated with supravalvar mitral membrane,
      coronary sinus defect and persistent left superior caval vein. 3D
      echocardiography navigates surgeon to successful repair.

PMID- 24726354
TI  - Shock-resistant ventricular fibrillation.

PMID- 24726355
TI  - Working hours, sleep duration and risk of coronary heart disease.

PMID- 24726357
TI  - Rewiring AMPK and mitochondrial retrograde signaling for metabolic control of
      aging and histone acetylation in respiratory-defective cells.
AB  - Abnormal respiratory metabolism plays a role in numerous human disorders. We find
      that regulation of overall histone acetylation is perturbed in respiratory
      incompetent (rho(0)) yeast. Because histone acetylation is highly sensitive to
      acetyl-coenzyme A (acetyl-CoA) availability, we sought interventions that
      suppress this rho(0) phenotype through reprogramming metabolism. Nutritional
      intervention studies led to the discovery that genetic coactivation of the
      mitochondrion-to-nucleus retrograde (RTG) response and the AMPK (Snf1) pathway
      prevents abnormal histone deacetylation in rho(0) cells. Metabolic profiling of
      signaling mutants uncovered links between chromatin-dependent phenotypes of
      rho(0) cells and metabolism of ATP, acetyl-CoA, glutathione, branched-chain amino
      acids, and the storage carbohydrate trehalose. Importantly, RTG/AMPK activation
      reprograms energy metabolism to increase the supply of acetyl-CoA to lysine
      acetyltransferases and extend the chronological lifespan of rho(0) cells. Our
      results strengthen the framework for rational design of nutrient supplementation
      schemes and drug-discovery initiatives aimed at mimicking the therapeutic
      benefits of dietary interventions.

PMID- 24726356
TI  - Folliculin controls lung alveolar enlargement and epithelial cell survival
      through E-cadherin, LKB1, and AMPK.
AB  - Spontaneous pneumothoraces due to lung cyst rupture afflict patients with the
      rare disease Birt-Hogg-Dube (BHD) syndrome, which is caused by mutations of the
      tumor suppressor gene folliculin (FLCN). The underlying mechanism of the lung
      manifestations in BHD is unclear. We show that BHD lungs exhibit increased
      alveolar epithelial cell apoptosis and that Flcn deletion in mouse lung
      epithelium leads to cell apoptosis, alveolar enlargement, and an impairment of
      both epithelial barrier and overall lung function. We find that Flcn-null
      epithelial cell apoptosis is the result of impaired AMPK activation and increased
      cleaved caspase-3. AMPK activator LKB1 and E-cadherin are downregulated by Flcn
      loss and restored by its expression. Correspondingly, Flcn-null cell survival is
      rescued by the AMPK activator AICAR or constitutively active AMPK. AICAR also
      improves lung condition of Flcn(f/f):SP-C-Cre mice. Our data suggest that lung
      cysts in BHD may result from an underlying defect in alveolar epithelial cell
      survival, attributable to FLCN regulation of the E-cadherin-LKB1-AMPK axis.

PMID- 24726358
TI  - DNA ligase I is not essential for mammalian cell viability.
AB  - Of the three DNA ligases present in all vertebrates, DNA ligase I (Lig1) has been
      considered essential for ligating Okazaki fragments during DNA replication and
      thereby essential for cell viability. Here, we report the striking finding that a
      Lig1-null murine B cell line is viable. Surprisingly, the Lig1-null cells exhibit
      normal proliferation and normal immunoglobulin heavy chain class switch
      recombination and are not hypersensitive to a wide variety of DNA damaging
      agents. These findings demonstrate that Lig1 is not absolutely required for
      cellular DNA replication and repair and that either Lig3 or Lig4 can substitute
      for the role of Lig1 in joining Okazaki fragments. The establishment of a Lig1
      null cell line will greatly facilitate the characterization of DNA ligase
      function in mammalian cells, but the finding alone profoundly reprioritizes the
      role of ligase I in DNA replication, repair, and recombination.

PMID- 24726359
TI  - The RBBP6/ZBTB38/MCM10 axis regulates DNA replication and common fragile site
      stability.
AB  - Faithful DNA replication is essential for the maintenance of genome integrity.
      Incomplete genome replication leads to DNA breaks and chromosomal rearrangements,
      which are causal factors in cancer and other human diseases. Despite their
      importance, the molecular mechanisms that control human genome stability are
      incompletely understood. Here, we report a pathway that is required for human
      genome replication and stability. This pathway has three components: an E3
      ubiquitin ligase, a transcriptional repressor, and a replication protein. The E3
      ubiquitin ligase RBBP6 ubiquitinates and destabilizes the transcriptional
      repressor ZBTB38. This repressor negatively regulates transcription and levels of
      the MCM10 replication factor on chromatin. Cells lacking RBBP6 experience reduced
      replication fork progression and increased damage at common fragile sites due to
      ZBTB38 accumulation and MCM10 downregulation. Our results uncover a pathway that
      ensures genome-wide DNA replication and chromosomal stability.

PMID- 24726360
TI  - 3' UTR-dependent, miR-92-mediated restriction of Tis21 expression maintains
      asymmetric neural stem cell division to ensure proper neocortex size.
AB  - Mammalian neocortex size primarily reflects the number and mode of divisions of
      neural stem and progenitor cells. Cortical stem cells (apical progenitors)
      switching from symmetric divisions, which expand their population, to asymmetric
      divisions, which generate downstream neuronal progenitors (basal progenitors),
      start expressing Tis21, a so-called antiproliferative/prodifferentiative gene.
      Tis21 encodes a small (17.5 kDa), functionally poorly characterized protein and a
      relatively large (2 kb), highly conserved 3' UTR. Here, we show that mice lacking
      the Tis21 3' UTR develop a microcephalic neocortex with fewer neurons, notably in
      the upper layers. This reflects a progressive decrease in basal progenitors,
      which in turn is due to a fraction of apical progenitors prematurely switching
      from asymmetric self-renewing to symmetric self-consuming divisions. This switch
      is caused by the markedly increased Tis21 protein level resulting from lack of
      microRNA-, notably miR-92-, dependent restriction of Tis21 expression. Our data
      show that a premature onset of consumptive neural stem cell divisions can lead to
      microcephaly.

PMID- 24726361
TI  - Dendrite development regulated by the schizophrenia-associated gene FEZ1 involves
      the ubiquitin proteasome system.
AB  - Downregulation of the schizophrenia-associated gene DISC1 and its interacting
      protein FEZ1 positively regulates dendrite growth in young neurons. However,
      little is known about the mechanism that controls these molecules during neuronal
      development. Here, we identify several components of the ubiquitin proteasome
      system and the cell-cycle machinery that act upstream of FEZ1. We demonstrate
      that the ubiquitin ligase cell division cycle 20/anaphase-promoting complex
      (Cdc20/APC) controls dendrite growth by regulating the degradation of FEZ1.
      Furthermore, dendrite growth is modulated by BubR1, whose known function so far
      has been restricted to control Cdc20/APC activity during the cell cycle. The
      modulatory function of BubR1 is dependent on its acetylation status. We show that
      BubR1 is deacetylated by Hdac11, thereby disinhibiting the Cdc20/APC complex.
      Because dendrite growth is affected both in hippocampal dentate granule cells and
      olfactory bulb neurons upon modifying expression of these genes, we conclude that
      the proposed mechanism governs neuronal development in a general fashion.

PMID- 24726362
TI  - ARF and p53 coordinate tumor suppression of an oncogenic IFN-beta-STAT1-ISG15
      signaling axis.
AB  - The ARF and p53 tumor suppressors are thought to act in a linear pathway to
      prevent cellular transformation in response to various oncogenic signals. Here,
      we show that loss of p53 leads to an increase in ARF protein levels, which
      function to limit the proliferation and tumorigenicity of p53-deficient cells by
      inhibiting an IFN-beta-STAT1-ISG15 signaling axis. Human triple-negative breast
      cancer (TNBC) tumor samples with coinactivation of p53 and ARF exhibit high
      expression of both STAT1 and ISG15, and TNBC cell lines are sensitive to STAT1
      depletion. We propose that loss of p53 function and subsequent ARF induction
      creates a selective pressure to inactivate ARF and propose that tumors harboring
      coinactivation of ARF and p53 would benefit from therapies targeted against STAT1
      and ISG15 activation.

PMID- 24726363
TI  - Fly-FUCCI: A versatile tool for studying cell proliferation in complex tissues.
AB  - One promising approach for in vivo studies of cell proliferation is the FUCCI
      system (fluorescent ubiquitination-based cell cycle indicator). Here, we report
      the development of a Drosophila-specific FUCCI system (Fly-FUCCI) that allows one
      to distinguish G1, S, and G2 phases of interphase. Fly-FUCCI relies on
      fluorochrome-tagged degrons from the Cyclin B and E2F1 proteins, which are
      degraded by the ubiquitin E3-ligases APC/C and CRL4(Cdt2), during mitosis or the
      onset of S phase, respectively. These probes can track cell-cycle patterns in
      cultured Drosophila cells, eye and wing imaginal discs, salivary glands, the
      adult midgut, and probably other tissues. To support a broad range of
      experimental applications, we have generated a toolkit of transgenic Drosophila
      lines that express the Fly-FUCCI probes under control of the UASt, UASp, QUAS,
      and ubiquitin promoters. The Fly-FUCCI system should be a valuable tool for
      visualizing cell-cycle activity during development, tissue homeostasis, and
      neoplastic growth.

PMID- 24726364
TI  - Testing the role of myeloid cell glucose flux in inflammation and
      atherosclerosis.
AB  - Inflammatory activation of myeloid cells is accompanied by increased glycolysis,
      which is required for the surge in cytokine production. Although in vitro studies
      suggest that increased macrophage glucose metabolism is sufficient for cytokine
      induction, the proinflammatory effects of increased myeloid cell glucose flux in
      vivo and the impact on atherosclerosis, a major complication of diabetes, are
      unknown. We therefore tested the hypothesis that increased glucose uptake in
      myeloid cells stimulates cytokine production and atherosclerosis. Overexpression
      of the glucose transporter GLUT1 in myeloid cells caused increased glycolysis and
      flux through the pentose phosphate pathway but did not induce cytokines.
      Moreover, myeloid-cell-specific overexpression of GLUT1 in LDL receptor-deficient
      mice was ineffective in promoting atherosclerosis. Thus, increased glucose flux
      is insufficient for inflammatory myeloid cell activation and atherogenesis. If
      glucose promotes atherosclerosis by increasing cellular glucose flux, myeloid
      cells do not appear to be the key targets.

PMID- 24726365
TI  - Structure, mechanism, and specificity of a eukaryal tRNA restriction enzyme
      involved in self-nonself discrimination.
AB  - tRNA restriction by anticodon nucleases underlies cellular stress responses and
      self-nonself discrimination in a wide range of taxa. Anticodon breakage inhibits
      protein synthesis, which, in turn, results in growth arrest or cell death. The
      eukaryal ribotoxin PaT secreted by Pichia acaciae inhibits growth of
      Saccharomyces cerevisiae via cleavage of tRNA(Gln(UUG)). We find that recombinant
      PaT incises a synthetic tRNA(Gln(UUG)) stem-loop RNA by transesterification at a
      single site 3' of the wobble uridine, yielding 2',3'-cyclic phosphate and 5'-OH
      ends. Incision is suppressed by replacement of the wobble nucleobase with adenine
      or guanine. The crystal structure of PaT reveals a distinctive fold and active
      site, essential components of which are demonstrated by mutagenesis. Pichia
      acaciae evades self-toxicity via a distinctive intracellular immunity protein,
      ImmPaT, which binds PaT and blocks nuclease activity. Our results highlight the
      evolutionary diversity of tRNA restriction and immunity systems.

PMID- 24726366
TI  - MANF is indispensable for the proliferation and survival of pancreatic beta
      cells.
AB  - All forms of diabetes mellitus (DM) are characterized by the loss of functional
      pancreatic beta cell mass, leading to insufficient insulin secretion. Thus,
      identification of novel approaches to protect and restore beta cells is essential
      for the development of DM therapies. Mesencephalic astrocyte-derived neurotrophic
      factor (MANF) is an endoplasmic reticulum (ER)-stress-inducible protein, but its
      physiological role in mammals has remained obscure. We generated MANF-deficient
      mice that strikingly develop severe diabetes due to progressive postnatal
      reduction of beta cell mass, caused by decreased proliferation and increased
      apoptosis. Additionally, we show that lack of MANF in vivo in mouse leads to
      chronic unfolded protein response (UPR) activation in pancreatic islets.
      Importantly, MANF protein enhanced beta cell proliferation in vitro and
      overexpression of MANF in the pancreas of diabetic mice enhanced beta cell
      regeneration. We demonstrate that MANF specifically promotes beta cell
      proliferation and survival, thereby constituting a therapeutic candidate for beta
      cell protection and regeneration.

PMID- 24726367
TI  - Mnk2 alternative splicing modulates the p38-MAPK pathway and impacts Ras-induced
      transformation.
AB  - The kinase Mnk2 is a substrate of the MAPK pathway and phosphorylates the
      translation initiation factor eIF4E. In humans, MKNK2, the gene encoding for
      Mnk2, is alternatively spliced yielding two splicing isoforms with differing last
      exons: Mnk2a, which contains a MAPK-binding domain, and Mnk2b, which lacks it. We
      found that the Mnk2a isoform is downregulated in breast, lung, and colon tumors
      and is tumor suppressive. Mnk2a directly interacts with, phosphorylates,
      activates, and translocates p38alpha-MAPK into the nucleus, leading to activation
      of its target genes, increasing cell death and suppression of Ras-induced
      transformation. Alternatively, Mnk2b is pro-oncogenic and does not activate p38
      MAPK, while still enhancing eIF4E phosphorylation. We further show that Mnk2a
      colocalization with p38alpha-MAPK in the nucleus is both required and sufficient
      for its tumor-suppressive activity. Thus, Mnk2a downregulation by alternative
      splicing is a tumor suppressor mechanism that is lost in some breast, lung, and
      colon tumors.

PMID- 24726368
TI  - TSPAN2 is involved in cell invasion and motility during lung cancer progression.
AB  - In lung cancer progression, p53 mutations are more often observed in invasive
      tumors than in noninvasive tumors, suggesting that p53 is involved in tumor
      invasion and metastasis. To understand the nature of p53 function as a tumor
      suppressor, it is crucial to elucidate the detailed mechanism of the alteration
      in epithelial cells that follow oncogenic KRAS activation and p53 inactivation.
      Here, we report that KRAS activation induces epithelial-mesenchymal transition
      and that p53 inactivation is required for cell motility and invasiveness.
      Furthermore, TSPAN2, a transmembrane protein, is responsible for cell motility
      and invasiveness elicited by p53 inactivation. TSPAN2 is highly expressed in p53
      mutated lung cancer cells, and high expression of TSPAN2 is associated with the
      poor prognosis of lung adenocarinomas. TSPAN2 knockdown suppresses metastasis to
      the lungs and liver, enabling prolonged survival. TSPAN2 enhances cell motility
      and invasiveness by assisting CD44 in scavenging intracellular reactive oxygen
      species.

PMID- 24726369
TI  - Free radicals mediate systemic acquired resistance.
AB  - Systemic acquired resistance (SAR) is a form of resistance that protects plants
      against a broad spectrum of secondary infections. However, exploiting SAR for the
      protection of agriculturally important plants warrants a thorough investigation
      of the mutual interrelationships among the various signals that mediate SAR.
      Here, we show that nitric oxide (NO) and reactive oxygen species (ROS) serve as
      inducers of SAR in a concentration-dependent manner. Thus, genetic mutations that
      either inhibit NO/ROS production or increase NO accumulation (e.g., a mutation in
      S-nitrosoglutathione reductase [GSNOR]) abrogate SAR. Different ROS function
      additively to generate the fatty-acid-derived azelaic acid (AzA), which in turn
      induces production of the SAR inducer glycerol-3-phosphate (G3P). Notably, this
      NO/ROS->AzA->G3P-induced signaling functions in parallel with salicylic acid
      derived signaling. We propose that the parallel operation of NO/ROS and SA
      pathways facilitates coordinated regulation in order to ensure optimal induction
      of SAR.

PMID- 24726371
TI  - Abscisic acid analogs as chemical probes for dissection of abscisic acid
      responses in Arabidopsis thaliana.
AB  - Abscisic acid (ABA) is a phytohormone known to mediate numerous plant
      developmental processes and responses to environmental stress. In Arabidopsis
      thaliana, ABA acts, through a genetically redundant family of ABA receptors
      entitled Regulatory Component of ABA Receptor (RCAR)/Pyrabactin Resistant 1
      (PYR1)/Pyrabactin Resistant-Like (PYL) receptors comprised of thirteen homologues
      acting in concert with a seven-member set of phosphatases. The individual
      contributions of A. thaliana RCARs and their binding partners with respect to
      specific physiological functions are as yet poorly understood. Towards developing
      efficacious plant growth regulators selective for specific ABA functions and
      tools for elucidating ABA perception, a panel of ABA analogs altered specifically
      on positions around the ABA ring was assembled. These analogs have been used to
      probe thirteen RCARs and four type 2C protein phosphatases (PP2Cs) and were also
      screened against representative physiological assays in the model plant
      Arabidopsis. The 1'-O methyl ether of (S)-ABA was identified as selective in
      that, at physiologically relevant levels, it regulates stomatal aperture and
      improves drought tolerance, but does not inhibit germination or root growth.
      Analogs with the 7'- and 8'-methyl groups of the ABA ring replaced with bulkier
      groups generally retained the activity and stereoselectivity of (S)- and (R)-ABA,
      while alteration of the 9'-methyl group afforded an analog that substituted for
      ABA in inhibiting germination but neither root growth nor stomatal closure.
      Further in vitro testing indicated differences in binding of analogs to
      individual RCARs, as well as differences in the enzyme activity resulting from
      specific PP2Cs bound to RCAR-analog complexes. Ultimately, these findings
      highlight the potential of a broader chemical genetics approach for dissection of
      the complex network mediating ABA-perception, signaling and functionality within
      a given species and modifications in the future design of ABA agonists. 

PMID- 24726370
TI  - HIV-1 adaptation to antigen processing results in population-level immune evasion
      and affects subtype diversification.
AB  - The recent HIV-1 vaccine failures highlight the need to better understand virus
      host interactions. One key question is why CD8(+) T cell responses to two HIV-Gag
      regions are uniquely associated with delayed disease progression only in patients
      expressing a few rare HLA class I variants when these regions encode epitopes
      presented by ~30 more common HLA variants. By combining epitope processing and
      computational analyses of the two HIV subtypes responsible for ~60% of worldwide
      infections, we identified a hitherto unrecognized adaptation to the antigen
      processing machinery through substitutions at subtype-specific motifs. Multiple
      HLA variants presenting epitopes situated next to a given subtype-specific motif
      drive selection at this subtype-specific position, and epitope abundances
      correlate inversely with the HLA frequency distribution in affected populations.
      This adaptation reflects the sum of intrapatient adaptations, is predictable,
      facilitates viral subtype diversification, and increases global HIV diversity.
      Because low epitope abundance is associated with infrequent and weak T cell
      responses, this most likely results in both population-level immune evasion and
      inadequate responses in most people vaccinated with natural HIV-1 sequence
      constructs. Our results suggest that artificial sequence modifications at subtype
      specific positions in vitro could refocus and reverse the poor immunogenicity of
      HIV proteins.

PMID- 24726372
TI  - Diterpenoids and phenylethanoid glycosides from the roots of Clerodendrum bungei
      and their inhibitory effects against angiotensin converting enzyme and alpha
      glucosidase.
AB  - Abietane derivatives, bungnates A, B, 15-dehydrocyrtophyllone A and 15-dehydro-17
      hydroxycyrtophyllone A, and two phenylethanoid glycosides, bunginoside A and
      3",4"-di-O-acetylmartynoside, together with nine known abietane derivatives and
      fourteen known phenylethanoid glycosides, were isolated from dried roots of
      Clerodendrum bungei. Their structures were determined on the basis of detailed
      spectroscopic analyses and acidic hydrolysis. The absolute configuration of
      bunginoside A was established from analysis of CD data. Selected compounds were
      evaluated for inhibitory effects against angiotensin converting enzyme (ACE) and
      alpha-glucosidase. 15-Dehydrocyrtophyllone A showed an ACE inhibitory effect, and
      verbascoside, leucosceptoside A and isoacteoside exhibited strong inhibitory
      capacity against alpha-glucosidase. 

PMID- 24726373
TI  - Highly selective dummy molecularly imprinted polymer as a solid-phase extraction
      sorbent for five bisphenols in tap and river water.
AB  - A simple and fast method for both dummy template selection and polymer
      composition optimization is proposed here. A series of dummy templates for
      bisphenols imprinting were screened by running them on a non-imprinted polymer
      (NIP) column with porogen solvent as mobile phase. The tested dummy templates
      mainly involved bisphenol S (BPS), bromobisphenol A (TBBPA), bisphenol F (BPF),
      bisphenol E (BPE), bisphenol B (BPB), bisphenol AF (BPAF), 2,2',6,6'-tetramethyl
      4,4'-sulfonyldiphenol (BS-TM) and 4,4'-diaminodiphenylmethane (DADPM). Different
      monomers and porogens were also investigated for BPS and DADPM using the same
      method. BPS dummy template was finally selected with acetonitrile and 4-VP as
      porogen and monomer. The resulting dummy molecularly imprinted polymer (DMIP)
      achieved superior affinities for BPF, BPE, BPA, BPB and BPAF with imprinting
      factors 14.5, 13.8, 8.7, 5.7 and 4.2, respectively. An efficient method based on
      BPS-DMIP-SPE coupled with HPLC-UV was developed for selective extraction of BPF,
      BPE, BPA, BPB and BPAF in water samples. The method showed excellent recoveries
      (89.4-102.0%) and precision (RSD 0.3-4.8%, n=5) for tap and river water samples
      spiked at three concentration levels each (40, 200 and 1000ngL(-1)). The
      detection limits ranged between 2.2 and 3.8ngL(-1) with a sample volume of 500mL.
      The result demonstrated the superiority of the optimized method for selective
      extraction of BPs in water samples at the ngL(-1) level. 

PMID- 24726374
TI  - Direct enantioseparation of underivatized aliphatic 3-hydroxyalkanoic acids with
      a quinine-based zwitterionic chiral stationary phase.
AB  - While aliphatic 2-hydroxyalkanoic acids have been more or less successfully
      enantioseparated with various chiral stationary phases by HPLC and GC, analogous
      applications on underivatized aliphatic 3-hydroxyalkanoic acids are completely
      absent in the scientific literature. With the aim of closing this gap, the
      enantioseparation of 3-hydroxybutyric acid, 3-hydroxydecanoic acid and 3
      hydroxymyristic acid has been performed with two ion-exchange type chiral
      stationary phases (CSPs): one containing the anion-exchange type tert-butyl
      carbamoyl quinine chiral selector motif (Chiralpak QN-AX), and the other carrying
      the new zwitterionic variant based on trans-(S,S)-2-aminocyclohexanesulfonic acid
      derivatized quinine carbamate (Chiralpak ZWIX(+)) as the chiral selector and
      enantiodiscriminating element, respectively. The zwitterionic enantiorecognition
      material provided better results in terms of enantioselectivity and resolution
      compared to the anion-exchanger CSP at reduced retention times due to the
      intramolecular counterion effect imposed by the sulfonic acid moiety and its
      competition with the 3-hydroxyalkanoic acid analyte for ionic interaction at the
      quininium-anion exchanger site. It is thus recommended as the CSP of first choice
      for enantioseparations of the class of aliphatic 3-hydroxyalkanoic acids. With
      use of polar organic eluent composed of ACN/MeOH/AcOH - 95/5/0.05 (v/v/v), a good
      compromise in terms of analysis time and enantioresolution quality was
      accomplished. The major experimental variables have been investigated for
      optimization of the resolution and allowed to derive information on the
      enantiorecognition mechanism. Corresponding Chiralpak ZWIX(-), based on pseudo
      enantiomeric selector derived from quinidine and trans-(R,R)-2
      aminocyclohexanesulfonic acid with opposite configurations provided reversed
      enantiomer elution orders. It has further to be stressed that these separations
      can be obtained with mass spectrometry compatible mobile phases. 

PMID- 24726375
TI  - Biomechanics of first ray hypermobility: an investigation on joint force during
      walking using finite element analysis.
AB  - Hypermobility of the first ray is suggested to contribute to hallux valgus. The
      investigation of first ray hypermobility focused on the mobility and range of
      motion that based on manual examination. The load transfer mechanism of the first
      ray is important to understand the development and pathomechanism of hallux
      valgus. In this study, we investigated the immediate effect of the joint
      hypermobility on the metatarsocuneiform and metatarsophalangeal joint loading
      through a reduction of the stiffness of the foot ligaments. A three-dimensional
      foot model was constructed from a female aged 28 via MRI. All foot and ankle
      bones, including two sesamoids and the encapsulated bulk tissue were modeled as
      3D solid parts, linking with ligaments of shell elements and muscles connectors.
      The stance phase of walking was simulated by the boundary and loading conditions
      obtained from gait analysis of the same subject. Compared with the normal foot,
      the hypermobile foot had higher resultant metatarsocuneiform and
      metatarsophalangeal joint forces. The increases accounted for 18.6% and 3.9% body
      weight. There was also an abrupt change of metatarsocuneiform joint force in the
      medial-lateral direction. The predicted results represented possible risk of
      joint problems and metatarsus primus varus. 

PMID- 24726376
TI  - In vivo challenging of polymyxins and levofloxacin eye drop against multidrug
      resistant Pseudomonas aeruginosa keratitis.
AB  - The purposes of this study were to establish a rabbit multidrug-resistant
      Pseudomonas aeruginosa (MDRP) keratitis model, and test the efficacy of
      levofloxacin, colistin methanesulfate (CL-M), colistin sulfate (CL-S) and
      polymyxin B (PL-B) against MDRP infection. In a rabbit eye, making a 2-mm
      circular corneal excision, and MDRP strain #601 or representative P. aeruginosa
      strain IID1210 were instilled into the corneal concavity. IID1210 was used to
      confirm this model developed P. aeruginosa keratitis. After MDRP keratitis
      developed, we treated the eyes with levofloxacin, CL-M, CL-S or PL-B eye drops.
      The infected eyes were evaluated by clinical score, histopathological examination
      and viable bacterial count (CFU). Rabbits developed MDRP keratitis reproducibly
      after instilled the bacteria into the corneal lesion. MDRP produced severe
      keratitis similarly with IID1210, as shown by slit lamp examination and clinical
      score. In MDRP keratitis models, clinical scores and viable bacterial counts were
      significantly lower in levofloxacin- and CL-M-treated groups compared with PBS
      treated group, but the magnitudes of reduction were not remarkable. However,
      clinical scores were dramatically lowered in CL-S- and PL-B-treated groups
      compared with PBS-treated group. CL-S- and PL-B-treated group were kept corneal
      translucency and little influx of polymorphonuclear neutrophils in
      histopathological examination. In addition, both CL-S- and PL-B-treated groups
      were not detected viable bacteria in infected cornea. Using our MDRP keratitis
      model, we showed that topical levofloxacin and CL-M are not adequately effective,
      while CL-S and PL-B are efficacious in controlling MDRP keratitis. Especially, PL
      B, which is commercially available eye drop, might be most effective against
      MDRP.

PMID- 24726377
TI  - Fulminant colitis from Clostridium difficile infection, the epidemic strain
      ribotype 027, in Japan.
AB  - In December 2012, a 32-year-old woman with no previous medical history and no
      previous antibiotic treatment had a fever and diarrhea 2 days after a cesarean
      section in which cefazolin was used as a prophylactic antimicrobial agent. She
      was transferred to our hospital 5 days after the cesarean for severe colitis. A
      rapid test of stool for Clostridium difficile toxin A and B was positive.
      Although oral vancomycin (0.5-2.0 g/day) and intravenous immunoglobulin (5 g/day)
      were administered after her transfer, 7 days after admission emergency
      exploratory surgery was performed because of poor response to therapy. Bowel
      perforation was noted and a temporary colostomy was created without colectomy.
      Vancomycin (2.0 g/day) was administered via the colostomy, in addition to a
      vancomycin enema (2.0 g/day), oral metronidazole (1500 mg/day), and oral
      vancomycin (2.0 g/day). Three days after the operation, linezolid (1200 mg/day
      IV) was added. She was treated with antibiotics against C. difficile for a total
      of 18 days after the operation. The same strain was not isolated from other
      patients in the same ward. Microbiological analysis of the isolate revealed
      housekeeping gene (tpi), toxin A gene (tcdA), toxin B gene (tcdB), and binary
      toxin gene (cdtA and cdtB). DNA sequencing of tcdC revealed a base 117 deletion
      and contained an 18-bp tcdC deletion. PCR ribotyping showed ribotype 027
      patterns. The MIC of moxifloxacin was >32 MUg/ml, indicating resistance to
      fluoroquinolones. This isolate was considered as the epidemic strain. Our case of
      fulminant colitis is apparently the first case involving the epidemic strain
      ribotype 027 in Japan.

PMID- 24726378
TI  - Quantitative 3D MRI reveals limited intra-lesional bony overgrowth at 1 year
      after microfracture-based cartilage repair.
AB  - OBJECTIVE: Intra-lesional bony overgrowth (BO) identified during or following
      cartilage repair treatment is being frequently described through subjective
      reports focusing primarily on incidence. Our objective was to quantify the exact
      volume of intra-lesional BO at 12 months post-cartilage repair treatment, to
      determine if a correlation exists between the extent of BO and clinical outcomes,
      and to visualize and characterize the BO. DESIGN: MRI scans were systematically
      obtained during a randomized clinical trial for cartilage repair (Stanish et al.,
      2013) that compared two microfracture-based treatments in 78 patients. Semi
      automated morphological segmentation of pre-treatment, 1 and 12 months post
      treatment scans utilizing a programmed anatomical atlas for all knee bone and
      cartilage structures permitted three-dimensional reconstruction, quantitative
      analysis, as well as qualitative characterization and artistic visualization of
      BO. RESULTS: Limited intra-lesional BO representing only 5.8 +/- 5.7% of the
      original debrided cartilage lesion volume was found in 78 patients with available
      MRIs at 12 months. The majority (80%) of patients had very little BO (<10%). Most
      occurrences of BO carried either spotty (56.4%) or planar (6.4%) morphological
      features, and the remaining balance (37.2%) was qualitatively unobservable by
      eye. Pre-existing BO recurred at 12 months in the same intra-lesional location in
      36% of patients. No statistical correlations were found between BO and clinical
      outcomes. CONCLUSIONS: Intra-lesional BO following microfracture-based treatments
      may not be as severe as previously believed, its incidence is partly explained by
      pre-existing conditions, and no relationship to clinical outcomes exists at 12
      months. Morphologically, observable BO was categorized as comprising either
      spotty or planar bone.

PMID- 24726379
TI  - Fixation of a double-coated titanium-hydroxyapatite focal knee resurfacing
      implant: a 12-month study in sheep.
AB  - OBJECTIVE: Focal cartilage lesions according to International Cartilage Repair
      Society (ICRS) grade 3-4 in the medial femoral condyle may progress to
      osteoarthritis. When treating such focal lesions with metallic implants a sound
      fixation to the underlying bone is mandatory. We developed a monobloc unipolar
      cobalt-chrome (Co-Cr) implant with a double coating; first a layer of
      commercially pure titanium (c.p.Ti) on top of which a layer of hydroxyapatite
      (HA) was applied. We hypothesised that such a double coating would provide long
      lasting and adequate osseointegration. DESIGN (MATERIALS AND METHODS): Unilateral
      medial femoral condyles of 10 sheep were operated. The implants were inserted in
      the weight-bearing surface and immediate weight-bearing was allowed. Euthanasia
      was performed at 6 (three animals) or 12 months (six animals). Osseointegration
      was analysed with micro-computer tomography (CT), light microscopy and
      histomorphometric analyses using backscatter scanning electron microscopy (B-SEM)
      technique. RESULTS: At 6 months one specimen out of three showed small osteolytic
      areas at the hat and at 12 months two specimens out of six showed small
      osteolytic areas at the hat, no osteolytical areas were seen around the peg at
      any time point. At both time points, a high total bone-to-implant contact was
      measured with a mean (95% confidence interval - CI) of 90.6 (79-102) at 6 months
      and 92.3 (89-95) at 12 months, respectively. CONCLUSIONS: A double coating (Ti +
      HA) of a focal knee resurfacing Co-Cr implant was presented in a sheep animal
      model. A firm and consistent bond to bone under weight-bearing conditions was
      shown up to 1 year.

PMID- 24726380
TI  - Differences in proprioception, muscle force control and comfort between
      conventional and new-generation knee and ankle orthoses.
AB  - The aim of this study was to compare muscle force control and proprioception
      between conventional and new-generation experimental orthoses. Sixteen healthy
      subjects participated in a single-blind controlled trial in which two different
      types of orthosis were applied to the dominant knee or ankle, while the following
      variables were evaluated: muscle force control (accuracy), joint position sense,
      kinesthesia, static balance as well as subjective outcomes. The use of
      experimental orthoses resulted in better force accuracy during isometric knee
      extensions compared to conventional orthoses (P=0.005). Moreover, the use of
      experimental orthoses resulted in better force accuracy during concentric
      (P=0.010) and eccentric (P=0.014) ankle plantar flexions and better knee joint
      kinesthesia in the flexed position (P=0.004) compared to conventional orthoses.
      Subjective comfort (P<0.001) and preference scores were higher with experimental
      orthoses compared to conventional ones. In conclusion, orthosis type affected
      static and dynamic muscle force control, kinesthesia, and perceived comfort in
      healthy subjects. New-generation experimental knee and ankle orthoses may thus be
      recommended for prophylactic joint bracing during physical activity and to
      improve the compliance for orthosis use, particularly in patients who require
      long-term bracing. 

PMID- 24726381
TI  - Roles of heat shock factor 1 in neuronal response to fetal environmental risks
      and its relevance to brain disorders.
AB  - Prenatal exposure of the developing brain to various environmental challenges
      increases susceptibility to late onset of neuropsychiatric dysfunction; still,
      the underlying mechanisms remain obscure. Here we show that exposure of embryos
      to a variety of environmental factors such as alcohol, methylmercury, and
      maternal seizure activates HSF1 in cerebral cortical cells. Furthermore, Hsf1
      deficiency in the mouse cortex exposed in utero to subthreshold levels of these
      challenges causes structural abnormalities and increases seizure susceptibility
      after birth. In addition, we found that human neural progenitor cells
      differentiated from induced pluripotent stem cells derived from schizophrenia
      patients show higher variability in the levels of HSF1 activation induced by
      environmental challenges compared to controls. We propose that HSF1 plays a
      crucial role in the response of brain cells to prenatal environmental insults and
      may be a key component in the pathogenesis of late-onset neuropsychiatric
      disorders.

PMID- 24726382
TI  - Dynorphin acts as a neuromodulator to inhibit itch in the dorsal horn of the
      spinal cord.
AB  - Menthol and other counterstimuli relieve itch, resulting in an antipruritic state
      that persists for minutes to hours. However, the neural basis for this effect is
      unclear, and the underlying neuromodulatory mechanisms are unknown. Previous
      studies revealed that Bhlhb5(-/-) mice, which lack a specific population of
      spinal inhibitory interneurons (B5-I neurons), develop pathological itch. Here we
      characterize B5-I neurons and show that they belong to a neurochemically distinct
      subset. We provide cause-and-effect evidence that B5-I neurons inhibit itch and
      show that dynorphin, which is released from B5-I neurons, is a key neuromodulator
      of pruritus. Finally, we show that B5-I neurons are innervated by menthol-,
      capsaicin-, and mustard oil-responsive sensory neurons and are required for the
      inhibition of itch by menthol. These findings provide a cellular basis for the
      inhibition of itch by chemical counterstimuli and suggest that kappa opioids may
      be a broadly effective therapy for pathological itch. 

PMID- 24726383
TI  - AMPK at the nexus of energetics and aging.
AB  - When energy supply is low, organisms respond by slowing aging and increasing
      resistance to diverse age-related pathologies. Targeting the mechanisms
      underpinning this response may therefore treat multiple disorders through a
      single intervention. Here, we discuss AMP-activated protein kinase (AMPK) as an
      integrator and mediator of several pathways and processes linking energetics to
      longevity. Activated by low energy, AMPK is both prolongevity and druggable, but
      its role in some pathologies may not be beneficial. As such, activating AMPK may
      modulate multiple longevity pathways to promote healthy aging, but unlocking its
      full potential may require selective targeting toward substrates involved in
      longevity assurance. 

PMID- 24726385
TI  - The complement inhibitor CD59 regulates insulin secretion by modulating
      exocytotic events.
AB  - Type 2 diabetes is triggered by reduced insulin production, caused by genetic and
      environmental factors such as inflammation originating from the innate immune
      system. Complement proteins are a component of innate immunity and kill non-self
      cells by perforating the plasma membrane, a reaction prevented by CD59. Human
      pancreatic islets express CD59 at very high levels. CD59 is primarily known as a
      plasma membrane protein in membrane rafts, but most CD59 protein in pancreatic
      beta cells is intracellular. Removing extracellular CD59 disrupts membrane rafts
      and moderately stimulates insulin secretion, whereas silencing intracellular CD59
      markedly suppresses regulated secretion by exocytosis, as demonstrated by TIRF
      imaging. CD59 interacts with the exocytotic proteins VAMP2 and Syntaxin-1. CD59
      expression is reduced by glucose and in rodent diabetes models but upregulated in
      human diabetic islets, potentially reflecting compensatory reactions. This
      unconventional action of CD59 broadens the established view of innate immunity in
      type 2 diabetes. 

PMID- 24726384
TI  - Targeting lactate dehydrogenase--a inhibits tumorigenesis and tumor progression
      in mouse models of lung cancer and impacts tumor-initiating cells.
AB  - The lactate dehydrogenase-A (LDH-A) enzyme catalyzes the interconversion of
      pyruvate and lactate, is upregulated in human cancers, and is associated with
      aggressive tumor outcomes. Here we use an inducible murine model and demonstrate
      that inactivation of LDH-A in mouse models of NSCLC driven by oncogenic K-RAS or
      EGFR leads to decreased tumorigenesis and disease regression in established
      tumors. We also show that abrogation of LDH-A results in reprogramming of
      pyruvate metabolism, with decreased lactic fermentation in vitro, in vivo, and ex
      vivo. This was accompanied by reactivation of mitochondrial function in vitro,
      but not in vivo or ex vivo. Finally, using a specific small molecule LDH-A
      inhibitor, we demonstrated that LDH-A is essential for cancer-initiating cell
      survival and proliferation. Thus, LDH-A can be a viable therapeutic target for
      NSCLC, including cancer stem cell-dependent drug-resistant tumors. 

PMID- 24726387
TI  - Effects of low carbohydrate diets on energy and nitrogen balance and body
      composition in rats depend on dietary protein-to-energy ratio.
AB  - OBJECTIVES: Truly ketogenic rodent diets are low in carbohydrates but also low in
      protein. The aim of this study was to differentiate effects of ketosis, low
      carbohydrate (LC) and/or low-protein intake on energy and nitrogen metabolism.
      METHODS: We studied the nitrogen balance of rats fed LC diets with varying
      protein contents: LC diets consisted of 75/10, 65/20 and 55/30 percent of fat to
      protein (dry matter), respectively, and were iso-energetically pair-fed to a
      control (chow) diet to 12-wk-old male Wistar rats (n = 6 per diet). Previous
      studies demonstrated only LC75/10 was truly ketogenic. Food, fecal, and urine
      samples, as well as carcasses were collected and analyzed for heat of combustion
      and nitrogen (Kjeldahl method). Blood samples were analyzed for plasma protein,
      albumin, and triacylglycerol. RESULTS: All LC groups displayed less body weight
      gain, and the degree of reduction was inversely related to digestible crude
      protein intake (daily weight gain compared with chow: LC75/10: -50%; LC55/30: 
      20%). Nitrogen excretion by urine was related to digestible protein intake (chow:
      0.23 +/- 0.02 g nitrogen/d; LC75/10: 0.05 +/- 0.01 g nitrogen/d). Renal energy
      excretion was closely associated with intake of digestible crude protein (r =
      0.697) and renal nitrogen excretion (r = 0.769). Energy-to-nitrogen ratio in
      urine was nearly doubled with LC75/10 compared with all other groups. Total body
      protein was highest with chow and lowest with LC75/10. Rats fed with LC75/10
      displayed features of protein deficiency (reduced growth and nitrogen balance,
      hypoproteinemia, depletion of body protein, and increased body and liver fat),
      whereas the effects with the non-ketogenic diets LC65/20 and LC55/30 were less
      pronounced. CONCLUSION: These results suggest that truly ketogenic LC diets in
      growing rats are LC diets that are also deficient in protein for growth.

PMID- 24726386
TI  - The GPIHBP1-LPL complex is responsible for the margination of triglyceride-rich
      lipoproteins in capillaries.
AB  - Triglyceride-rich lipoproteins (TRLs) undergo lipolysis by lipoprotein lipase
      (LPL), an enzyme that is transported to the capillary lumen by an endothelial
      cell protein, GPIHBP1. For LPL-mediated lipolysis to occur, TRLs must bind to the
      lumen of capillaries. This process is often assumed to involve heparan sulfate
      proteoglycans (HSPGs), but we suspected that TRL margination might instead
      require GPIHBP1. Indeed, TRLs marginate along the heart capillaries of wild-type
      but not Gpihbp1-/- mice, as judged by fluorescence microscopy, quantitative
      assays with infrared-dye-labeled lipoproteins, and EM tomography. Both cell
      culture and in vivo studies showed that TRL margination depends on LPL bound to
      GPIHBP1. Notably, the expression of LPL by endothelial cells in Gpihbp1-/- mice
      did not restore defective TRL margination, implying that the binding of LPL to
      HSPGs is ineffective in promoting TRL margination. Our studies show that GPIHBP1
      bound LPL is the main determinant of TRL margination.

PMID- 24726388
TI  - Shopper marketing nutrition interventions.
AB  - Grocery stores represent a context in which a majority of people's food purchases
      occur. Considering the nutrition quality of the population's food intake has
      dramatically decreased, understanding how to improve food choice in the grocery
      store is paramount to healthier living. In this work, we detail the type of
      financial resources from which shoppers could draw (i.e., personal income and
      benefits from government food assistance programs to low income populations) and
      explain how these financial resources are allocated in the grocery store (i.e.,
      planned, unplanned, error). Subsequently, we identify a conceptual framework for
      shopper marketing nutrition interventions that targets unplanned fruit and
      vegetable purchases (i.e., slack, or willingness to spend minus list items).
      Targeting slack for fresh fruit and vegetable purchases allows retailers to
      benefit economically (i.e., fruit and vegetables are higher margin) and allows
      shoppers to improve their nutrition without increasing their budgets (i.e.,
      budget neutrality). We also provide preliminary evidence of what in-store
      marketing of fresh fruits and vegetables could entail by modifying grocery carts
      and grocery floors to provide information of what is common, normal, or
      appropriate fruit and vegetable purchases. In each example, fresh fruit and
      vegetable purchases increased and evidence suggested shopper budget neutrality.
      To provide context for these results, we detail measurement tools that can be
      used to measure shopper behaviors, purchases, and consumption patterns. Finally,
      we address theoretical, practical, and policy implications of shopper marketing
      nutrition interventions. 

PMID- 24726389
TI  - The social environment during a post-match video presentation affects the
      hormonal responses and playing performance in professional male athletes.
AB  - This study examined the social environment effects during a post-match video
      presentation on the hormonal responses and match performance in professional male
      rugby union players. The study participants (n=12) watched a 1-hour video of
      mixed content (player mistakes and successes) from a match played 1 day earlier
      in the presence of; (1) strangers who were bigger (SB), (2) strangers who were
      smaller (SS), (3) friends who were bigger (FB) and (4) friends who were smaller
      (FS). The salivary testosterone (T) and cortisol (C) responses to a physical
      stress test were assessed 3 days later, along with pre-match T levels and match
      ranked performance 6-7 days later. All treatments were associated with elevated T
      responses (% change from baseline) to the stress test with SS>SB and FB>FS. The C
      stress responses after the SS and SB interventions were both greater than FS and
      FB. On match-day, the FB approach was linked to higher T concentrations than SB
      and better ranked performance than FS and SS. The subsequent testing of a
      population sub-group (n=8) across a video (V) and a non-video (NV) presentation
      in a neutral social environment produced similar stress-test and performance
      outcomes, but pre-match T concentrations differed (V>NV). In conclusion, the
      presence of other males during a post-match video assessment had some influence
      on the hormonal responses of male athletes and match performance in the week that
      followed. Thus, the social environment during a post-match assessment could
      moderate performance and recovery in elite sport and, in a broader context, could
      be a possible modulator of human stress responses.

PMID- 24726390
TI  - Resistance and aerobic exercises do not affect post-exercise energy compensation
      in normal weight men and women.
AB  - BACKGROUND: Previous research has reported no effect of exercise modality
      (aerobic vs. resistance) on energy intake (EI). However, the relatively low
      energy cost of resistance training, the absence of total energy expenditure (TEE)
      measurements and the short duration of these studies justify further
      investigation. OBJECTIVE: To evaluate the effects of exercise modality on EI,
      TEE, non-exercise activity thermogenesis (NEAT) and post-exercise energy
      compensation (PEEC) measured acutely, as well as for 10 and 34 h following
      exercise. DESIGN: Eight men and 8 women participated in three randomized
      crossover sessions: aerobic-based exercise, resistance-based exercise, and
      sedentary control. Exercise energy expenditure (ExEE) was continuously measured
      (indirect calorimetry) throughout the exercise sessions, which were designed to
      produce an isocaloric ExEE of 4 kcal/kg body weight. TEE and EI were monitored
      for 34 h post-exercise with biaxial accelerometers and a validated food menu,
      respectively. RESULTS: There were no differences in EI between exercise
      modalities acutely, as well as 10 and 34 h following exercise. However, a
      modality by sex interaction was noted for acute EI. Men ate more after the
      resistance than after the aerobic session (1567+/-469; 1255+/-409 kcal,
      respectively; P=0.034), while no differences were seen in women (568+/-237; 648+/
      270 kcal, respectively; P=NS). No differences in TEE, NEAT and PEEC were found
      10h and 34 h post-exercise, while a positive correlation (r=0.897; P<0.01) was
      found between both modalities across participants for PEEC. CONCLUSION: Exercise
      modality does not impact PEEC when ExEE is controlled. Our results also show that
      within-individual PEEC seems to be relatively constant across exercise modality.

PMID- 24726391
TI  - Acid-induced hyperalgesia and anxio-depressive comorbidity in rats.
AB  - Fibromyalgia is a prevalent disorder characterized by chronic widespread pain
      (CWP) and complex comorbid symptoms. A CWP model is developed through repeated
      unilateral intramuscular injections of acid saline resulting in bilateral
      mechanical hyperalgesia in rats. The present study aims to evaluate whether both
      anxious and depressive comorbidities exist in this acid-induced pain model,
      similarly to patients with CWP syndromes. The anxiety-like behaviors were
      evaluated using the open field and elevated plus maze tests, and depression-like
      behaviors were measured by the forced swimming, sucrose consumption, and sucrose
      preference tests. The pain group receiving acidic saline displayed significantly
      lower paw withdrawal thresholds for 4weeks than animals in the vehicle group
      after repetitive intramuscular injections. The pain group showed a significantly
      shorter duration of exploring the central zone of the open field and the open
      arms of the elevated plus maze compared to the vehicle group. The pain group had
      a significantly lower preference for and consumption of the hedonic sucrose.
      Moreover, rats with chronic pain showed significantly longer immobility than the
      vehicle group in the forced swimming test. The results indicate that psychiatric
      behaviors are exacerbated in the CWP model. This study provides evidence for the
      validity of the acid-induced pain model analogous to patients with CWP syndromes.

PMID- 24726392
TI  - Cost-effectiveness analysis of intensity modulated radiation therapy versus 3
      dimensional conformal radiation therapy for anal cancer.
AB  - PURPOSE: To compare the cost-effectiveness of intensity modulated radiation
      therapy (IMRT) and 3-dimensional conformal radiation therapy (3D-CRT) for anal
      cancer and determine disease, patient, and treatment parameters that influence
      the result. METHODS AND MATERIALS: A Markov decision model was designed with the
      various disease states for the base case of a 65-year-old patient with anal
      cancer treated with either IMRT or 3D-CRT and concurrent chemotherapy. Health
      states accounting for rates of local failure, colostomy failure, treatment
      breaks, patient prognosis, acute and late toxicities, and the utility of
      toxicities were informed by existing literature and analyzed with deterministic
      and probabilistic sensitivity analysis. RESULTS: In the base case, mean costs and
      quality-adjusted life expectancy in years (QALY) for IMRT and 3D-CRT were $32,291
      (4.81) and $28,444 (4.78), respectively, resulting in an incremental cost
      effectiveness ratio of $128,233/QALY for IMRT compared with 3D-CRT. Probabilistic
      sensitivity analysis found that IMRT was cost-effective in 22%, 47%, and 65% of
      iterations at willingness-to-pay thresholds of $50,000, $100,000, and $150,000
      per QALY, respectively. CONCLUSIONS: In our base model, IMRT was a cost
      ineffective strategy despite the reduced acute treatment toxicities and their
      associated costs of management. The model outcome was sensitive to variations in
      local and colostomy failure rates, as well as patient-reported utilities relating
      to acute toxicities.

PMID- 24726393
TI  - Analysis of peptidase activities of a cathepsin B-like (TcoCBc1) from Trypanosoma
      congolense.
AB  - The substrate specificity of TcoCBc1 was evaluated using two internally quenched
      fluorescent peptide libraries with randomized sequences designed to detect
      carboxydipeptidase (Abz-GXXZXK(Dnp)-OH) and endopeptidase (Abz-GXXZXXQ-EDDnp)
      activities at acidic and neutral pHs, respectively. All the data obtained with
      TcoCBc1 were compared with those of human cathepsin B, including the pH profiles
      of the hydrolytic reactions. The most relevant observation is the preference of
      TcoCBc1 for substrates with a pair of acidic amino acids at positions P(2) and
      P(1) for its carboxydipeptidase activity and the well acceptance for E and D at
      P(1) position for endopeptidase activity. These peculiar preferences for
      negatively charged groups of TcoCBc1 and its requirements for carboxydipeptidase
      activity were also observed on Abz labeled analogues of bradykinin (Abz
      RPPG(?)FSAFR-OH, Abz-RPPG(?)FS(?)AF-OH, Abz-RPPG(?)DE(?)AF-OH) and angiotensin I
      (Abz-DR(?)VYIHAFHL-OH), where (?) indicates the cleavage site. TcoCBc1 was
      modeled based on the atomic coordinates of the cathepsin B from Trypanosoma
      brucei and the positively charged environment in TcoCBc1 catalytic site contrasts
      with the negatively charged environment in human cathepsin B. The preferences of
      S1 and S2 subsites of TcoCBc1 for acidic amino acids have to be taken into
      consideration for future studies of physiological roles of TcoCBc1 as for
      instance in apoptotic processes of Trypanosoma congolense.

PMID- 24726394
TI  - Presence of hypogammaglobulinemia and abnormal antibody responses in GATA2
      deficiency.

PMID- 24726395
TI  - Minimal invasive biopsy of intraconal expansion by PET/CT/MRI image-guided
      navigation: a new method.
AB  - Intraorbital tumours are often undetected for a long period and may lead to
      compression of the optic nerve and loss of vision. Although CT, MRI's and
      ultrasound can help in determining the probable diagnosis, most orbital tumours
      are only diagnosed by surgical biopsy. In intraconal lesions this may prove
      especially difficult as the expansions are situated next to sensitive anatomical
      structures (eye bulb, optic nerve). In search of a minimally invasive access to
      the intraconal region, we describe a method of a three-dimensional, image-guided
      biopsy of orbital tumours using a combined technique of hardware fusion between
      (18)F-FDG Positron Emission Tomography ((18)F-FDG PET), magnetic resonance
      imaging (MRI) and Computed Tomography (CT). METHOD AND MATERIAL: We present 6
      patients with a total of 7 intraorbital lesions, all of them suffering from
      diplopia and/or exophthalmos. There were 3 female and 3 male patients. The
      patients age ranged from 20 to 75 years. One of the patients showed beginning
      loss of vision. Another of the patients had lesions in both orbits. The decision
      to obtain image-guided needle biopsies for treatment planning was discussed and
      decided at an interdisciplinary board comprising other sub-specialities
      (ophthalmology, neurosurgery, maxillofacial surgery, ENT, plastic surgery). All
      patients underwent 3D imaging preoperatively ((18)F-FDG PET/CT or (18)F-FDG
      PET/CT plus MRI). Data was transferred to 3D navigation system. Access to the
      lesions was planned preoperatively on a workstation monitor. Biopsy-needles were
      then calibrated intraoperatively and all patients underwent three-dimensional
      image-guided needle biopsies under general anaesthesia. RESULTS: 7 biopsies were
      performed. The histologic subtype was idiopathic orbital inflammation in 2
      lesions, lymphoma in 2, Merkel cell carcinoma in 1, hamartoma in 1 and 1
      malignant melanoma. The different pathologies were subsequently treated in
      consideration of the actual state of the art. In cases where surgical removal of
      the lesion was performed the histological diagnosis was confirmed in all cases.
      CONCLUSION: There is a wide range of possible treatment modalities for orbital
      tumours depending on the nature of the lesion. Histological diagnosis is
      mandatory to select the proper management and operation. The presented method
      allows minimal-invasive biopsy even in deep intraconal lesions, enabling the
      surgeon to spare critical anatomical structures. Vascular lesions such as
      cavernous haemangioma, tumour of the lacrimal gland or dermoid cysts present a
      contraindication and have to be excluded.

PMID- 24726396
TI  - Differences in saccharin preference and genetic alterations of the Tas1r3 gene
      among senescence-accelerated mouse strains and their parental AKR/J strain.
AB  - The senescence-accelerated mouse (SAM) is used as an animal model of senescence
      acceleration and age-associated disorders. SAM is derived from unexpected crosses
      between the AKR/J and unknown mouse strains. There are nine senescence-prone
      (SAMP) strains and three senescence-resistant (SAMR) strains. Although SAMP
      strains exhibit strain-specific and age-related pathological changes, the genes
      responsible for the pathologic changes in SAMP strains have not been
      comprehensively identified. In the present study, we evaluated sweet taste
      perception using the two-bottle test. We compared genotypes of the taste related
      gene, Tas1r3, using SAM strains and the parental AKR/J strain. The two-bottle
      test revealed that SAMR1 (R1), SAMP6 (P6), SAMP8 (P8), and SAMP10 (P10) mice were
      saccharin-preferring strains, whereas AKR/J did not prefer saccharin. All
      genotypes of the R1, P6, P8, and P10 strains at the polymorphic sites in Tas1r3,
      which is known to influence saccharin preference, were identical to those of
      C57BL6/J, a well-known saccharin-preferring strain, and were completely different
      from those of the parental AKR/J strain. These genetic alterations in SAM strains
      appear to arise from an unknown strain that is thought to have been crossed with
      AKR/J initially. 

PMID- 24726397
TI  - Development of a non-invasive polysomnography technique for dogs (Canis
      familiaris).
AB  - Recently dogs (Canis familiaris) have been demonstrated to be a promising model
      species for studying human behavior as they have adapted to the human niche and
      developed human-like socio-cognitive skills. Research on dog behavior, however,
      has so far almost exclusively focused on awake functioning. Here we present a
      self-developed non-invasive canine polysomnography method that can easily be
      applied to naive pet dogs. N=22 adult pet dogs (with their owners present) and
      N=12 adult humans participated in Study I. From these subjects, N=7 dogs returned
      on two more occasions for Study II. In Study I, we give a descriptive analysis of
      the sleep electroencephalogram of the dog and compare it to human data. In order
      to validate our canine polysomnography method in Study II, we compare the sleep
      macrostructure and the EEG spectrum of dogs after a behaviorally active day
      without sleep versus passive day with sleep. In Study I, we found that dogs'
      sleep EEG resembled that of human subjects and was generally in accordance with
      previous literature using invasive technology. In Study II, we show that
      similarly to previous results on humans daytime load of novel experiences and
      sleep deprivation affects the macrostructural and spectral aspects of subsequent
      sleep. Our results validate the family dog as a model species for studying the
      effects of pre-sleep activities on the EEG pattern under natural conditions and,
      thus, broaden the perspectives of the rapidly growing fields of canine cognition
      and sleep research. 

PMID- 24726398
TI  - If it makes you feel bad, don't do it! Egoistic rather than altruistic empathy
      modulates neural and behavioral responses in moral dilemmas.
AB  - According to Greene et al.'s dual-process theory, the differential involvement of
      emotional processes would explain the different patterns of moral judgments
      people typically produce when faced with Trolley- and Footbridge-type dilemmas.
      As a relevant factor, dispositional empathy is known to motivate prosocial
      behaviors, thus playing a central role in moral judgment and behavior. The
      present study was aimed at investigating how behavioral and neural correlates of
      moral decision-making are modulated by the cognitive and affective dimensions of
      empathy. Thirty-seven participants were presented with 30 Footbridge-type and 30
      Trolley-type dilemmas. Participants were required to decide between two options:
      letting some people die (non-utilitarian) vs. killing one person to save more
      people (utilitarian). Event-related potentials (ERPs) were recorded stimulus
      locked to a "decision slide". Response choices and ratings of valence and arousal
      were also collected. Trait empathy was measured through the Interpersonal
      Reactivity Index (IRI), assessing both the cognitive and affective dimensions.
      Scores on the Empathic Concern affective subscale of the IRI positively predicted
      unpleasantness experienced during decision-making for all dilemmas. On the other
      hand, for Footbridge-type dilemmas only, scores on the Personal Distress
      affective subscale predicted negatively the mean percentages of utilitarian
      choices and positively the mean amplitudes of the P260, an ERP component
      reflecting an immediate emotional reaction during decision-making. It is
      concluded that "self-oriented" feelings of anxiety and unease, rather than "other
      oriented" feelings of concern, affect behavioral choices and emotion-related
      cortical activity in Footbridge-type moral dilemmas. 

PMID- 24726399
TI  - Advances in understanding the interrelations between leptin resistance and
      obesity.
AB  - Obesity, which has developed into a global epidemic, is a risk factor in most
      chronic diseases and some forms of malignancy. The discovery of leptin in 1994
      has opened a new field in obesity research. Currently, we know that leptin is the
      primary signal from energy stores and exerts negative feedback effects on energy
      intake. However, most individuals with diet-induced obesity (DIO) develop leptin
      resistance, which is characterized by elevated circulating leptin levels and
      decreased leptin sensitivity. To date, though various mechanisms have been
      proposed to explain leptin resistance, the exact mechanisms of leptin resistance
      in obesity are poorly understood. Consequently, it's an important issue worth
      discussing regarding what the exact interrelations between leptin resistance and
      obesity are. Here, we review the latest advancements in the molecular mechanisms
      of leptin resistance and the exact interrelations between leptin resistance,
      obesity, and obesity-related diseases, in order to supply new ideas for the study
      of obesity. 

PMID- 24726400
TI  - Verrucous localized lymphedema of genital areas: clinicopathologic report of 18
      cases of this rare entity.
AB  - BACKGROUND: Localized lymphedema is a nonneoplastic condition associated with
      obesity and predominantly involving the legs. This condition has distinctive
      clinical and histologic features and only rarely has been mentioned in the
      dermatologic literature. OBJECTIVE: We sought to evaluate the clinical and
      histopathologic features. METHODS: The clinicopathologic features in patients
      with localized lymphedema of the genital region were studied. RESULTS: We
      identified 18 patients with localized lymphedema clinically presenting as large
      polypoid or verrucous lesions. The patients were 5 men and 13 women with a mean
      age of 46.5 years. Twelve patients were obese at diagnosis. Thirteen patients
      presented with tumors involving the vulva, 4 patients with tumors in the penis
      and scrotum, and 1 patient with scrotal and pubic lesions. Histologically, all
      cases showed marked dermal edema along with dilated lymphatic spaces,
      fibroplasia, and verrucous epidermal changes (papillomatous and hyperplastic
      epidermis). LIMITATIONS: Only 18 cases were included in our study. CONCLUSIONS:
      This condition is an uncommon and recently described entity that could
      potentially be clinically and histologically misdiagnosed as a neoplasm; thus, it
      needs to be included in the differential diagnosis of polypoid and verrucous skin
      tumors with extensive dermal edema and fibroplasia.

PMID- 24726401
TI  - Different patterns of skin manifestations associated with parvovirus B19 primary
      infection in adults.
AB  - BACKGROUND: Skin involvement is reported during primary parvovirus B19 infection
      in adults. OBJECTIVES: We sought to describe the cutaneous presentations
      associated with parvovirus B19 primary infection in adults. METHODS: We conducted
      a descriptive, retrospective, multicenter study. The patients included (>18 years
      old) had well-established primary infections with parvovirus B19. RESULTS: Twenty
      nine patients were identified between 1992 and 2013 (17 women, 12 men). The
      elementary dermatologic lesions were mostly erythematous (86%) and often purpuric
      (69%). Pruritus was reported in 48% of cases. The rash predominated on the legs
      (93%), trunk (55%), and arms (45%), with a lower frequency of facial involvement
      (20%). Four different but sometimes overlapping patterns were identified (45%):
      exanthema, which was reticulated and annular in some cases (80%); the gloves-and
      socks pattern (24%); the periflexural pattern (28%); and palpable purpura (24%).
      LIMITATIONS: The limitations of this study were its retrospective design and
      possible recruitment bias in tertiary care centers. CONCLUSION: Our findings
      suggest that primary parvovirus B19 infection is associated with polymorphous
      skin manifestations with 4 predominant, sometimes overlapping, patterns. The
      acral or periflexural distribution of the rash and the presence of purpuric or
      annular/reticulate lesions are highly suggestive of parvovirus B19 infection.

PMID- 24726402
TI  - Inactivation of the prelimbic rather than infralimbic cortex impairs acquisition
      and expression of formalin-induced conditioned place avoidance.
AB  - Conditioned place avoidance (CPA) paradigm has been used to investigate the
      affective component of pain. Although the anterior cingulate cortex (ACC) has
      been demonstrated to play an important role in the affective aspect of pain,
      whether the other prefrontal subdivisions are involved in pain-related aversion
      is unknown. The present study investigated the role of the prelimbic cortex (PL)
      and infralimbic cortex (IL) in the acquisition and expression of formalin-induced
      CPA (F-CPA) in rats. GABAA receptor agonist muscimol was bilaterally
      microinjected into PL/IL before or after the formalin-paired training, to explore
      the effect of temporary inactivation of PL/IL on the acquisition and expression
      of F-CPA, respectively. The results showed that inactivation of PL rather than IL
      impaired the acquisition and expression of F-CPA. Moreover, the PL inactivation
      did not block the acquisition of LiCl-induced CPA, suggesting that PL may be
      specifically implicated in the pain-emotion related encoding. These results
      indicate that PL but not IL is involved in the aversive dimension of pain. 

PMID- 24726403
TI  - Hippocampal vulnerability and subacute response following varied blast
      magnitudes.
AB  - Clinical outcomes from blast neurotrauma are associated with higher order
      cognitive functions such as memory, problem solving skills and attention. Current
      literature is limited to a single overpressure exposure or repeated exposures at
      the same level of overpressure and is focused on the acute response (<3 days). In
      an attempt to expand the understanding of neuropathological and molecular changes
      of the subacute response (7 days post injury), we used an established rodent
      model of blast neurotrauma. Three pressure magnitudes (low, moderate and high)
      were used to evaluate molecular injury thresholds. Immunohistochemical analysis
      demonstrated increased cleaved caspase-3 levels and loss of neuronal population
      (NeuN+) within the hippocampus of all pressure groups. On the contrary, selective
      activation of microglia was observed in the low blast group. In addition,
      increased astrocytes (GFAP), membrane signal transduction protein (Map2k1) and
      calcium regulator mechanosensitive protein (Piezo 2) were observed in the
      moderate blast group. Results from gene expression analysis suggested ongoing
      neuroprotection, as brain-derived neurotrophic factor (BDNF), glial-derived
      neurotrophic factor (GDNF) and Mn and CuZn superoxide dismutases (SOD) all
      increased in the low and moderate blast groups. Ongoing neuroprotection was
      further supported by increased SOD levels observed in the moderate group using
      immunohistochemistry. The gene expression level of glutamate aspartate
      transporter (GLAST) was upregulated in the low, but downregulated in the high
      blast group, while no changes were found in the moderate group. Overall, the data
      shown here provides evidence of a diverse neuroprotective and glial response to
      various levels of blast exposure. This mechanistic role of neuroprotection is
      vital in understanding ongoing cellular stress, both at the gene and protein
      levels, in order to develop interventional studies for the prognosis of injury. 

PMID- 24726404
TI  - Fritz Lickint.

PMID- 24726405
TI  - Prevention of invasive pneumococcal disease: new evidence.

PMID- 24726406
TI  - Effectiveness of ten-valent pneumococcal conjugate vaccine against invasive
      pneumococcal disease in Brazil: a matched case-control study.
AB  - BACKGROUND: In March 2010, Brazil introduced the ten-valent pneumococcal
      conjugate vaccine (PCV10), which was licensed based on non-inferiority of
      immunological correlates of protection compared with the seven-valent vaccine.
      The schedule comprised three primary doses at ages 2 months, 4 months, and 6
      months, and a booster dose at age 12 months. A single catch-up dose was offered
      for children aged 12-23 months at the time of introduction. We assessed PCV10
      effectiveness against invasive pneumococcal disease in Brazilian children.
      METHODS: Invasive pneumococcal disease, defined as isolation of Streptococcus
      pneumoniae from blood, cerebrospinal fluid, or another normally sterile site, was
      identified in children age-eligible for at least one PCV10 dose through
      laboratory-based and hospital-based surveillance in ten states in Brazil from
      March 1, 2010, until Dec 31, 2012. We aimed to identify four age-matched and
      neighbourhood-matched controls for each case. We used conditional logistic
      regression and calculated PCV10 effectiveness as (1-adjusted matched odds ratio)
      * 100% for vaccine-type and vaccine-related serotypes (ie, in the same serogroup
      as a vaccine serotype). FINDINGS: In 316 cases (median age 13.2 months, range 2.6
      53.1) and 1219 controls (13.3 months, 2.6-53.1), the adjusted effectiveness of an
      age-appropriate PCV10 schedule was 83.8% (95% CI 65.9-92.3) against vaccine
      serotypes, and 77.9% (41.0-91.7) against vaccine-related serotypes. Serotype
      specific effectiveness was shown for the two most common vaccine serotypes-14
      (87.7%, 60.8-96.1) and 6B (82.8%, 23.8-96.1)-and serotype 19A (82.2%, 10.7-96.4),
      a serotype related to vaccine serotype 19F. A single catch-up dose in children
      aged 12-23 months was effective against vaccine-type disease (68.0%, 17.6-87.6).
      No significant effectiveness was shown against non-vaccine serotypes for age
      appropriate or catch-up schedules. INTERPRETATION: In the routine immunisation
      programme in Brazil, PCV10 prevents invasive disease caused by vaccine serotypes.
      PCV10 might provide cross-protection against some vaccine-related serotypes.
      FUNDING: Brazilian Ministry of Health, Pan-American Health Organization, and US
      Centers for Disease Control and Prevention.

PMID- 24726407
TI  - Rapid spread and association of Schmallenberg virus with ruminant abortions and
      foetal death in Austria in 2012/2013.
AB  - Schmallenberg virus (SBV) has emerged in summer-autumn 2011 in north-western
      Europe. Since then, SBV has been continuously spreading over Europe, including
      Austria, where antibodies to SBV, as well as SBV genome, were first detected in
      autumn 2012. This study was performed to demonstrate the dynamics of SBV spread
      within Austria, after its probable first introduction in summer 2012. True
      seroprevalence estimates for cattle and small ruminates were calculated to
      demonstrate temporal and regional differences of infection. Furthermore, the
      probability of SBV genome detection in foetal tissues of aborted or stillborn
      cattle and small ruminants as well as in allantoic fluid samples from cows with
      early foetal losses was retrospectively assessed. SBV first reached Austria most
      likely in July-August 2012, as indicated by retrospective detection of SBV
      antibodies and SBV genome in archived samples. From August to October 2012, a
      rapid increase in seroprevalence to over 98% in cattle and a contemporaneous peak
      in the detection of SBV genome in foetal tissues and allantoic fluid samples was
      noted, indicating widespread acute infections. Notably, foetal malformations were
      absent in RT-qPCR positive foetuses at this time of the epidemic. SBV spread
      within Austrian cattle reached a plateau phase as early as October 2012, without
      significant regional differences in SBV seroprevalence (98.4-100%). Estimated
      true seroprevalences among small ruminates were comparatively lower than in
      cattle and regionally different (58.3-95.6% in October 2012), potentially
      indicating an eastward spread of the infection, as well as different infection
      dynamics between cattle and small ruminants. Additionally, the probability of SBV
      genome detection over time differed significantly between small ruminant and
      cattle samples subjected to RT-qPCR testing.

PMID- 24726408
TI  - Anti-HCV activity of the Chinese medicinal fungus Cordyceps militaris.
AB  - Persistent hepatitis C virus (HCV) infection causes chronic liver diseases and is
      a global health problem. Although the sustained virologic response rate in the
      treatment of genotype 1 using new triple therapy (pegylated-interferon,
      ribavirin, and telaprevir/boceprevir) has been improved by more than 70%, several
      severe side effects such as skin rash/ageusia and advanced anemia have become a
      problem. Under these circumstances, a new type of anti-HCV oral drug with few
      side effects is needed. Our recently developed HCV drug assay systems, including
      the HuH-7 cell line-derived OR6 and AH1R, and the Li23 cell line-derived ORL8 and
      ORL11, allow genome-length HCV RNAs (several strains of genotype 1b) encoding
      renilla luciferase to replicate efficiently. Using these systems as anti-HCV
      candidates, we have identified numerous existing medicines that can be used
      against HCV with few side effects, such as statins and teprenon. To obtain
      additional anti-HCV candidates, we evaluated a number of oral health supplements,
      and found that the capsule but not the liquid form of Cordyceps militaris (CM)
      (Ascomycotinanorth, North Chinese caterpillar fungus), which is used as a Chinese
      herbal medicine, exhibited moderate anti-HCV activity. In combination with
      interferon-alpha or ribavirin, CM exhibited an additive inhibitory effect. Among
      the main components of CM, cordycepin, but not ergosterol, contributed to the
      anti-HCV activity of CM. In consideration of all these results, we suggest that
      CM would be useful as an oral anti-HCV agent in combination with interferon-alpha
      and/or ribavirin. 

PMID- 24726409
TI  - Passage number of porcine embryonic germ cells affects epigenetic status and
      blastocyst rate following somatic cell nuclear transfer.
AB  - Epigenetic instability of donor cells due to long-term in vitro culture may
      influence the success rate of subsequent somatic cell nuclear transfer (SCNT).
      Therefore, the present study was designed (1) to investigate the epigenetic
      changes after prolonged culture in vitro of porcine embryonic germ (EG) cells,
      including differences in expression levels of both DNA methylation and
      demethylation-related genes and catalyses of histone modifications, and (2) to
      assess the efficiency of SCNT using EG cells from different passages. Results
      showed that genes either associated with DNA demethylation including DNMTs and
      TET1 or genes related to histone acetylation including HDACs were highly
      expressed in EG cells at higher passages when compared to EG cells at lower
      passages. In addition, the expression level of H3K27me3 functional methylase EZH2
      increased while no changes were observed on H3K27me3 demethylase JMJD3 in
      relation to passage number. Moreover, the expression levels of both the H3K4me3
      methylase MLL1 and the H3K4me3 demethylase RBP2 were increased at high passages.
      By using lower passage (numbers 3-5) EG cells as donor cells, the SCNT efficiency
      was significantly lower compared with use of fetal fibroblast donor cells.
      However, similar blastocyst rates were achieved when using higher passage
      (numbers 9-12) EG cells as donor cells. In conclusion, the present study suggests
      that the epigenetic status of EG cells change with increasing passage numbers,
      and that higher passage number EG cells are better primed for SCNT.

PMID- 24726410
TI  - Reproductive performance, semen quality, and fatty acid profile of spermatozoa in
      senescent broiler breeder roosters as enhanced by the long-term feeding of dried
      apple pomace.
AB  - Avian spermatozoa are characteristically high in polyunsaturated fatty acids
      which predispose them to lipoperoxidation, thereby diminishing their fertility.
      As a by-product, well-known for antioxidative properties, dried apple pomace (AP)
      was fed to aging Ross 308 breeder roosters (n=80) at the dietary inclusion levels
      of 0 (AP0), 10 (AP10), 20 (AP20), or 25 (AP25) percent for 14 consecutive weeks.
      Seminal traits were studied every other week. At the end of the trial, sperm
      fatty acids profile, seminal plasma total antioxidant capacity (TAC), fertility,
      hatchability, and hatchling quality were evaluated, using 240 artificially
      inseminated young hens. Dietary AP increased sperm motility and livability and
      decreased the seminal content of thiobarbituric acid reactive species. Dietary
      treatment and age interacted to positively affect sperm concentration and sperm
      membrane integrity. Feeding AP was associated with an increase in C20:4(n-6),
      C22:4(n-6), and total unsaturated fatty acids percentages. Birds in the AP25 and
      AP20 treatment groups respectively showed 6 and 7% increases in fertility rate.
      Interestingly, a higher hatchability rate was found for AP20 group, associated
      with a higher number of sperm penetration holes in the perivitelline membrane and
      a lower rate of early embryonic mortality. However, hatchling quality was not
      affected by dietary AP. Overall, these data suggest that AP could remarkably
      improve several sperm characteristics, seminal TAC, fertility, and hatchability
      rate in aging breeder roosters. These improvements were also associated with a
      higher content of total unsaturated FA in the sperm plasma membrane. Future
      studies are needed to disclose the causal mechanisms involved.

PMID- 24726411
TI  - Social correlates of total cancer in adults and the very old: UK Understanding
      Society Cohort, 2009-2010.
AB  - OBJECTIVE: Understanding of the social determinants of cancer in adults and the
      very old is still limited. The aim of this study was to provide recent evidence
      on the social correlates of adult total cancer in a national and population-based
      setting. STUDY DESIGN: A cross-sectional study in the recent years between 2009
      and 2010. METHOD: Data was retrieved and analysed from the UK Longitudinal
      Household Survey. Information on demographics, living and work conditions, self
      reported cancer and age of onset was obtained by household interview. Analyses
      included Chi-squared test, t-test, and multilevel logistic regression modelling.
      RESULTS: Of 50,994 people included in the cohort, 1623 (3.5%) had ever cancer. Of
      these, 1592 (98.0%) occurred in adulthood (16y+) and only 109 people had their
      first cancer (incident cancer) at the age when they were interviewed. In the
      middle-aged and young adults, being female (OR 1.57, 95%CI 1.20-2.06, P = 0.001
      and OR 2.04, 95%CI 1.07-3.87, P = 0.03, respectively), not born in the UK (OR
      0.54, 95%CI 0.34-0.88, P = 0.01 and OR 0.31, 95%CI 0.09-1.02, P = 0.05,
      respectively), and being obese/overweight (OR 1.49, 95%CI 1.07-2.07, P = 0.02 and
      OR 2.34, 95%CI 1.17-4.66, P = 0.02, respectively) were associated with total
      cancer. However, no associated social factors of cancer in the very old were
      found. Moreover, prevalence was higher in East Midlands (OR 1.73, 95%CI 1.00
      3.00, P = 0.05) but not other regions, compared to London region. CONCLUSION:
      Social environment seems to continue playing a role in the aetiology of cancer in
      adults, although novel and/or pooled investigation for the very old would be
      warranted.

PMID- 24726412
TI  - Spatiotemporal pattern of hand-foot-mouth disease in China: an analysis of
      empirical orthogonal functions.
AB  - OBJECTIVES: Hand-foot-mouth disease (HFMD) is the most common infectious disease
      in China. Spatial and temporal patterns of HFMD in China provide valuable
      information on the relationship between HFMD and the geographical environment,
      and help in the prediction of HFMD transmission. STUDY DESIGN: Cross-sectional
      study. METHODS: Total HFMD morbidity per 10 days from May 2008 to March 2009 was
      recorded in 1966 counties in China. Empirical orthogonal function (EOF) analysis
      was used to obtain spatial and temporal patterns of HFMD. RESULTS: The first five
      modes of HFMD morbidity explained 84.24% of the total variance. The dominant mode
      (first mode showing the highest variance) showed high HFMD morbidity in the
      western counties of Bohai Bay, the mid-south of China, the Yangtze River delta,
      the Pearl River delta and the areas bordering Vietnam from early May to late July
      2008. The second mode showed high HFMD morbidity in the western counties of Bohai
      Bay, the north-east of China, north of Xinjiang and the Yangtze River delta from
      late May to the middle of August 2008. The third mode showed high HFMD morbidity
      in the Yangtze River delta, the Pearl River delta and the middle of the Huaihe
      River basin in early May 2008. CONCLUSIONS: EOF analysis of HFMD morbidity shows
      the main spatiotemporal patterns and can explain variance in HFMD in China.

PMID- 24726413
TI  - Role of birthplace in chronic disease in adults and very old individuals:
      national cohorts in the UK and USA, 2009-2010.
AB  - OBJECTIVES: To understand the role of birthplace in chronic disease in adults and
      very old individuals. STUDY DESIGN: Two national and population-based studies (UK
      Longitudinal Household Survey and US National Health and Nutrition Examination
      Surveys) in 2009-2010 were included. METHOD: Information on demographics,
      lifestyle factors and self-reported chronic diseases was obtained by household
      interview. Analyses included Chi-squared test, t-test and logistic regression
      modelling. RESULTS: In the UK, there were more cases of heart failure and
      myocardial infarction in adults (aged 20-79 years) born in Scotland, and more
      cases of coronary heart disease in adults born in Northern Ireland. There were
      fewer cases of asthma, depression and hypothyroidism in adults born in Northern
      Ireland and not born in the UK, and fewer cases of cancer, chronic bronchitis and
      epilepsy in adults not born in the UK. In USA, there were fewer cases of asthma,
      cancer, chronic bronchitis, heart failure and heart attack, but more cases of
      liver disease in adults born in Mexico. Similarly, there were fewer cases of
      asthma, cancer and chronic bronchitis in adults born in other Spanish or non
      Spanish countries, although there were more cases of liver disease in other
      Spanish-born adults and more cases of diabetes in other non-Spanish-born adults.
      In very old (>=80 years) individuals, there were more cases of chronic bronchitis
      in those born in Wales, more cases of myocardial infarction in those born in
      Northern Ireland, and more cases of diabetes and liver disease in those not born
      in the UK. Overall, diabetes was more common in foreign-born adults, and
      respiratory illness and cancer were more common in native-born adults.
      CONCLUSIONS: It is suggested that future health policy and public health
      programmes should consider birthplace.

PMID- 24726414
TI  - The prevalence of physical activity and its associated factors among Malaysian
      adults: findings from the National Health and Morbidity Survey 2011.
AB  - OBJECTIVES: Despite the health-enhancing benefits of physical activity, a large
      segment of the Malaysian population does not engage in regular physical activity
      at the recommended level. This study aimed to determine physical activity
      patterns and the associated sociodemographic correlates of physical activity.
      STUDY DESIGN: Data on physical activity were obtained from the National Health
      and Morbidity Survey (NHMS) 2011, a nationally representative, population-based
      cross-sectional study. A two-stage stratified sampling method was used to select
      a representative sample of Malaysian adults aged 16 years and above. METHODS: A
      total of 19,145 adults aged 16 years and above were recruited, and face-to-face
      interviews were conducted using the International Physical Activity Questionnaire
      (IPAQ), short version. The correlates for physical activity were identified using
      multivariate analysis. RESULTS: In this study, 64.3% (95%CI: 63.1-65.5) of
      Malaysian adults aged 16 and above were physically active, but overall physical
      activity levels decreased with advancing age. Men, rural residents, 'other'
      ethnic groups, and married women were more likely to demonstrate higher levels of
      physical activity. CONCLUSION: Approximately 65% of Malaysian adults were
      physically active. However, it is recommended that health promotions for active
      lifestyles should be targeted to the least active segments, which constitute more
      than a quarter of the Malaysian population.

PMID- 24726415
TI  - Survivin and pAkt as potential prognostic markers in squamous cell carcinoma of
      the head and neck.
AB  - OBJECTIVE: The purpose of our study was to investigate the expression patterns of
      cell cycle regulatory proteins and members of the epidermal growth factor
      receptor (EGFR) signaling pathway in squamous cell carcinoma of the head and neck
      (HNSCC). STUDY DESIGN: The expression levels of survivin, Bub1 B (budding
      uninhibited by benzimidazoles 1 homolog beta), PLK-1 (polo-like kinase 1), Ki-67,
      cyclin D1, p53, EGFR, pMAPK (phosphorylated mitogen-activated protein kinase),
      pAkt (phosphorylated protein kinase B), and PTEN (phosphatase and tensin homolog)
      were studied in a series of 180 tumor samples obtained from HNSCC surgical
      resections, 50 metastatic lymph node samples, and 72 corresponding noncancerous
      epithelium samples. Protein expression analysis was performed by
      immunohistochemical staining. The results were correlated with clinicopathologic
      features and survival data. RESULTS: Prognostic significance could be found only
      for the markers survivin and pAkt. Only the marker combination of cyclin D1 and
      p53 had positive prognosis potential regarding overall survival. CONCLUSIONS:
      Both pAkt and survivin show a positive correlation with distant metastases and
      may have utility as predictors of long-term outcomes for patients with HNSCC.

PMID- 24726416
TI  - Iodine penetration and glycogen distribution in vital staining of oral mucosa
      with iodine solution.
AB  - OBJECTIVE: To assess and compare iodine penetration and glycogen distribution in
      a vital staining of oral mucosa with iodine solution. STUDY DESIGN: Twenty
      samples were obtained including both iodine-stained and -unstained mucosa.
      Intraepithelial iodine was examined using frozen sections. Glycogen distribution
      was assessed by periodic acid-Schiff staining and transmission electron
      microscopy. RESULTS: Iodine accumulation was observed mainly superficially and in
      the upper and middle thirds of prickle cell layers, with glycogen in almost the
      whole epithelium except for the para- and basal cell layers. The pattern of
      iodine and glycogen distribution was classified into 3 types (full-, surround-,
      and scatter-type). The iodine color was mainly derived from the cells with full-
      and surround-type distributed glycogen in the upper half of the oral epithelium.
      CONCLUSIONS: The results of this study suggested that iodine penetrated into
      nonkeratinized oral epithelium and reacted mainly with intraepithelial glycogen
      homogeneously distributed in the cytoplasm.

PMID- 24726417
TI  - Automated analysis of bone marrow aspirates from dogs with haematological
      disorders.
AB  - Automated analysis of bone marrow (BM) aspirates is a useful 'pre-microscopical'
      screen to identify hypocellular samples and those with potentially abnormal
      cells. In order to determine whether automated analysis could also be used to
      identify haemopoietic abnormalities, EDTA-anticoagulated BM aspirates from 43
      dogs were analysed using the Advia 2120 instrument. Corresponding Wright-stained
      BM smears were evaluated microscopically to determine smear quality, cell
      composition and 500-cell differential counts, and correlation to automated
      analysis parameters was computed. Leucocyte cytograms generated by the automated
      analyzer were scrutinized and compared with those of 'normal' BM. Twenty-three
      neoplastic and 20 non-neoplastic samples were analysed, including samples from 10
      cases of acute myeloid leukaemia, four cases of acute lymphocytic leukaemia, four
      cases of chronic lymphocytic leukaemia, one case of chronic neutrophilic
      leukaemia, three cases of multiple myeloma, one case of myelodysplastic syndrome,
      five cases of non-regenerative immune-mediated haemolytic anaemia, one case of
      immune-mediated neutropenia, three cases of immune-mediated thrombocytopenia, six
      cases of inflammatory disease, three samples with myelotoxicity and two samples
      analysed for staging of neoplasia. Automated white blood cell (WBC) counts
      correlated significantly with smear cellularity, particle cellularity and
      particle number. There was a significant difference in WBC counts of samples with
      insufficient versus sufficient particles. Significant correlations between Advia
      percent neutrophils and microscopical determination of marrow segmented
      neutrophils/neutrophilic granulocyte reserve, Advia percent lymphocytes and
      microscopical determination of lymphocytes/rubricytes, Advia percent large
      unstained cells and microscopical determination of myeloblasts/promyelocytes and
      between Advia percent eosinophils and manual determination of eosinophils were
      identified. This suggested that Advia WBC counts may be used to approximate BM
      sample quality and that Advia differential counts may predict marrow granulocyte
      reserve and lymphocyte/rubricyte stores. Distinct and consistent alterations in
      cytogram patterns were observed in cases of acute leukaemia, but were less
      obvious in chronic leukaemia. Complete automated BM analysis was performed in
      approximately 2 min, while staining and coverslipping of BM slides required
      approximately 30 min. Hence, although automated analysis should not supplant
      microscopical evaluation of BM, it can provide useful ancillary information in a
      short time and flag potentially inadequate or abnormal samples.

PMID- 24726419
TI  - Experimental and modeling studies of ultrasound-assisted release of phenolics
      from oak chips into model wine.
AB  - The enhancement of release of oak-related compounds from oak chips during wine
      aging with oak chips may interest the winemaking industry. In this study, the 25
      kHz ultrasound waves were used to intensify the mass transfer of phenolics from
      oak chips into a model wine. The influences of acoustic energy density (6.3-25.8
      W/L) and temperature (15-25  degrees C) on the release kinetics of total
      phenolics were investigated systematically. The results exhibited that the total
      phenolic yield released was not affected by acoustic energy density significantly
      whereas it increased with the increase of temperature during sonication.
      Furthermore, to describe the mechanism of mass transfer of phenolics in model
      wine under ultrasonic field, the release kinetics of total phenolics was
      simulated by both a second-order kinetic model and a diffusion model. The
      modeling results revealed that the equilibrium concentration of total phenolics
      in model wine, the initial release rate and effective diffusivity of total
      phenolics generally increased with acoustic energy density and temperature. In
      addition, temperature had a negative effect on the second-order release rate
      constant whereas acoustic energy density had an opposite effect.

PMID- 24726418
TI  - Isolated right ventricular dysfunction in patients with human immunodeficiency
      virus.
AB  - BACKGROUND: HIV-infected individuals are at increased risk for pulmonary
      hypertension and cardiomyopathy, portending a poor prognosis. Right ventricular
      (RV) dysfunction is associated with worse outcomes in these conditions, yet its
      prevalence is poorly defined in HIV. We sought to determine the prevalence of RV
      dysfunction in an outpatient HIV cohort. METHODS: Echocardiograms were evaluated
      from 104 HIV-infected adults. Measurements included estimated pulmonary arterial
      systolic pressure (PASP) and several measures of RV function, including tricuspid
      annular plane systolic excursion (TAPSE), RV longitudinal myocardial strain
      (RVLMS), RV fractional area change (RVFAC), and myocardial performance index
      (MPI). RESULTS: Sixteen subjects (15%) had PASP >35 mm Hg, yet RV function did
      not differ significantly from those with normal estimated PASP. RV dysfunction
      defined by RVFAC <35% occurred in 11%. RVLMS had a median value of -27.3%, and
      individuals below the median had lower TAPSE but no differences in left
      ventricular ejection fraction (LVEF), PASP, or other measures. Dyspnea was
      associated with the lowest quintile of RVLMS (>=-21.05%). There were 6 subjects
      with LVEF <50%, and these individuals had lower TAPSE but no differences in PASP
      or other RV functional measures. CONCLUSIONS: RV dysfunction was common as
      estimated PASP >35 mm Hg and LV dysfunction, but these findings did not
      cosegregate. RV dysfunction in HIV-infected individuals may be a separate entity
      from LV/global cardiomyopathy or pulmonary hypertension and deserves further
      study.

PMID- 24726420
TI  - Bronchiectases at early chest computed tomography in children with cystic
      fibrosis are associated with increased risk of subsequent pulmonary exacerbations
      and chronic pseudomonas infection.
AB  - BACKGROUND: Children with cystic fibrosis (CF) are often Pseudomonas aeruginosa
      (PsA) free and exhibit normal spirometry between the ages of 5 and 7. It is
      reported that computed tomography (CT) is more sensitive than FEV1 as an
      instrument in the identification of pulmonary disease. It is not known whether CF
      CT scores in childhood may be used to highlight children at risk of developing
      severe disease. AIMS: 1 - To assess the number of respiratory exacerbations
      (RTEs) during a follow-up period of 6 years and their correlation with the CF-CT
      scores in young CF children. 2 - To assess whether PsA-negative CF children with
      high chest CF-CT scores are more likely to develop chronic PsA lung infection.
      METHODS: 68 chest CT performed in patients without chronic PsA infection were
      scored. All patients (median age 7.8 years) had at least 4 clinical, functional
      and microbiologic assessments/year in the subsequent 6 years. RTE was defined as
      hospitalization and IV antibiotic treatment for respiratory symptoms. RESULTS:
      86.8% patients had <3 RTEs in the 6 year follow-up period. The number of RTEs in
      the 6 years subsequent to the CT scan was correlated to the bronchiectasis CT
      score (BCTS) (r = 0.612; p < 0.001) and to FEV1 at baseline (r = -0.495,
      p<0.001). A BCTS >= 17.5 identified patients with >3 RTEs during follow-up
      (sensitivity: 100%, specificity: 85%), while FEV1 did not. Only BCTS was
      significant in a logistic multivariate model (RR 1.15). BCTS was significantly
      lower and FEV1 higher in patients who did not develop chronic PsA infection by
      the end of the study. CONCLUSION: In CF children free from chronic PsA, both CT
      scores and FEV1 values demonstrate significant correlation with disease severity
      in the subsequent 6 years but CT score has higher predictive value in the
      identification of patients at risk.

PMID- 24726421
TI  - Childbirth related fears and psychological birth trauma in younger and older age
      adolescents.
AB  - AIM: The aim of this study is to explore childbirth fears on psychological birth
      trauma (PBT) by adolescent age. BACKGROUND: Among adults parity and intrapartum
      fears including fear of dying, loss of control, pain, and limited support have
      been associated with negative birth appraisal and symptoms of traumatic stress,
      defined here as PBT. METHODS: This cross-sectional study surveyed a convenience
      sample of 201 adolescents at a large, county hospital. RESULTS: Over 75% of
      adolescents perceived fear. Younger and older adolescents, similar in fears, were
      distinguished only by parity. The effects of parity, overall rating of fear, and
      father of baby absence were found to vary by age on birth appraisal; however,
      only parity varied by age on IES scores. CONCLUSIONS: All age adolescents can be
      fearful and will benefit with childbirth education and labor support to help
      reduce fears and subsequent PBT.

PMID- 24726422
TI  - B-type natriuretic peptide therapy in total artificial heart implantation: renal
      effects with early initiation.

PMID- 24726423
TI  - Device thrombosis in continuous-flow left ventricular assist devices: a new
      manifestation of Kounis syndrome?

PMID- 24726424
TI  - Pre-operative mortality risk assessment in patients with continuous-flow left
      ventricular assist devices: application of the HeartMate II risk score.
AB  - BACKGROUND: Survival with left ventricular assist device (LVAD) therapy is
      dependent on appropriate patient selection. The HeartMate II risk score (HMRS)
      was recently derived and validated to predict 90-day mortality in clinical trial
      patients with continuous-flow LVADs. The aim of this study was to test HMRS
      validity in predicting survival at our institution. METHODS: We performed a
      retrospective analysis of patients implanted with HeartMate II (HMII; Thoratec,
      Pleasanton, CA) LVADs from March 31, 2004 to September 20, 2012 at the Columbia
      University Medical Center (CUMC). Patients were stratified according to HMRS
      profiles (HMRS Low < 1.58, 1.58 <= HMRS Medium <= 2.48, HMRS High > 2.48)
      calculated using age, albumin, creatinine, international normalized ratio (INR)
      and center volume. Outcome was defined as survival at 90 days after device
      implantation. RESULTS: HeartMate II LVADs were implanted in 205 patients. Pre
      operative data from 201 patients were categorized into HMRS Low (n = 101; 1.04
      [0.64 to 1.31]), HMRS Medium (n = 73; 1.98 [1.78 to 2.25]) and HMRS High (n = 27,
      3.07 [2.70 to 3.43]) (p < 0.0001). Kaplan-Meier survival estimates at 90 days
      (HMRS Low 91.0 +/- 2.9%, HMRS Medium 91.7 +/- 3.2%, HMRS High 88.7 +/- 6.1%) and
      at 1 year (HMRS Low 85.5 +/- 3.8%, HMRS Medium 79.3 +/- 5.5%, HMRS High 82.4 +/-
      8.4%) after LVAD implantation were not statistically different (p = 0.43).
      Prediction of 90-day mortality by receiver operating characteristic was poor (AUC
      = 0.56). CONCLUSION: HMRS stratification poorly discriminates 90-day mortality
      after HMII LVAD implantation at our institution. Its generalizability as a
      universal prognostic score may be limited.

PMID- 24726425
TI  - Needling the heart to rejuvenate: the promise of intramyocardial injection of
      bone marrow stem cells.

PMID- 24726426
TI  - Successful treatment of refractory cutaneous warts using topical 3% cidofovir in
      a child after heart transplant.

PMID- 24726427
TI  - Sex differences in methamphetamine pharmacokinetics in adult rats and its
      transfer to pups through the placental membrane and breast milk.
AB  - BACKGROUND: Methamphetamine (METH) abuse is a growing health problem worldwide,
      and METH use during pregnancy not only endangers the mother's health but also the
      developing fetus. To provide better insight into these risks, we performed the
      following experiments. METHOD: First, we investigated how sex influences the
      pharmacokinetics of METH and amphetamine (AMP) in male and female rats.
      Subsequently, we simulated chronic exposure of prenatal infants to METH abuse by
      investigating brain and plasma levels of METH and AMP in dams and pups. Finally,
      we modeled chronic exposure of infants to METH via breast milk and investigated
      sex differences in pups with regard to drug levels and possible sensitization
      effect of chronic prenatal METH co-treatment. RESULTS: We observed significantly
      higher levels of METH and AMP in the plasma and brain of female rats compared to
      males. Additionally, brain concentrations of METH and AMP in pups exposed to METH
      prenatally were equivalent to 62.13% and 37.78% relative to dam, respectively.
      Plasma concentrations of AMP where equivalent to 100% of the concentration in
      dams, while METH was equivalent to only 36.98%. Finally, we did not observe a
      significant effect relative to sex with regard to METH/AMP levels or
      sensitization effects linked to prenatal METH exposure. CONCLUSION: We
      demonstrated that female rats display higher levels of METH and AMP, thus
      indicating a greater risk of addiction and toxicity. Furthermore, our data show
      that pups are exposed to both METH and AMP following dam exposure.

PMID- 24726428
TI  - Partner smoking and maternal cotinine during pregnancy: implications for negative
      control methods.
AB  - BACKGROUND: Comparison of the associations of maternal and mother's partner
      smoking with offspring outcomes is, in theory, a useful method for assessing
      whether there may be an intrauterine effect of tobacco exposure on these
      outcomes. However, this approach assumes that the effects of passive smoking from
      exposure to partner smoking during pregnancy are minimal. We evaluated this
      assumption using a biochemical measure of tobacco exposure in pregnant women.
      METHODS: Cotinine levels taken during the first trimester of pregnancy were
      measured in a sample of 3928 women from the Avon Longitudinal Study of Parents
      and Children. Median cotinine values were compared across categories of smoking
      heaviness (cigarettes per day) of the women during the first trimester and in non
      smoking women by the smoking heaviness of their partner. RESULTS: Cotinine levels
      were substantially higher in women who smoked compared to non-smokers (range of
      medians across smoking heaviness categories: 900-5362 ng/ml versus 20 ng/ml,
      interquartile range (IQR) (0-63) for non-smokers). In contrast, cotinine levels
      in non-smoking women were only very weakly related to partner smoking status
      (range of medians in women with smoking partners: 34-69 ng/ml versus 12 ng/ml,
      IQR (0-48) in women with non-smoking partners). CONCLUSIONS: Levels of tobacco
      exposure from partner smoking, as assessed by cotinine, were low in non-smoking
      pregnant women. This suggests that using mother's partner's smoking as a negative
      control for investigating intrauterine effects is valid.

PMID- 24726430
TI  - Hypothesis: a role for EBV-induced molecular mimicry in Parkinson's disease.
AB  - Current concepts regarding the pathogenesis of Parkinson's disease support a
      model whereby environmental factors conspire with a permissive genetic background
      to initiate the disease. The identity of the responsible environmental trigger
      has remained elusive. There is incontrovertible evidence that aggregation of the
      neuronal protein alpha-synuclein is central to disease pathogenesis. A novel
      hypothesis of Parkinson's pathogenesis, articulated by Braak and colleagues,
      implicates a pathogen acting in the olfactory mucosa and gastrointestinal tract
      as the inciting agent. In this point-of-view article, we hypothesize that alpha
      synuclein aggregation in Parkinson's disease is an Epstein-Barr virus (EBV)
      induced autoimmune phenomenon. Specifically, we have shown evidence for molecular
      mimicry between the C-terminal region of alpha-synuclein and a repeat region in
      the latent membrane protein 1 encoded by EBV. We hypothesize that, in genetically
      susceptible individuals, anti-EBV latent membrane protein antibodies targeting
      the critical repeat region cross react with the homologous epitope on alpha
      synuclein and induce its oligomerization. Consistent with the Braak's proposed
      pattern of spread, we contend that axon terminals in the lamina propria of the
      gut are among the initial targets, with subsequent spread of pathology to the
      CNS. While at this time, we can only provide evidence from the literature and
      preliminary findings from our own laboratory, we hope that our hypothesis will
      stimulate the development of tractable experimental systems that can be exploited
      to test it. Further support for an EBV-induced immune pathogenesis for
      Parkinson's disease could have profound therapeutic implications. 

PMID- 24726429
TI  - The impact of buprenorphine/naloxone treatment on HIV risk behaviors among HIV
      infected, opioid-dependent patients.
AB  - BACKGROUND: Opioid dependence is a major risk factor for HIV infection, however,
      the impact of buprenorphine/naloxone treatment on HIV risk behaviors among HIV
      infected opioid-dependent patients is unknown. METHODS: We conducted a
      longitudinal analysis of 303 HIV-infected opioid-dependent patients initiating
      buprenorphine/naloxone treatment. Outcomes included self-reported past 90-day
      needle-sharing and non-condom use. We assessed trends over the 12 months using
      the Cochran-Armitage trend test. Using generalized estimating equations, after
      multiple imputation, we determined factors independently associated with needle
      sharing and non-condom use, including time-updated variables. We then conducted a
      mediation analysis to determine whether substance use explained the relationship
      between time since treatment initiation and needle-sharing. RESULTS: Needle
      sharing decreased from baseline to the fourth quarter following initiation of
      buprenorphine/naloxone (9% vs. 3%, p<0.001), while non-condom use did not (23%
      vs. 21%, p=0.10). HIV risk behaviors did not vary based on the presence of a
      detectable HIV-1 RNA viral load. Patients who were homeless and used heroin,
      cocaine/amphetamines or marijuana were more likely to report needle-sharing.
      Heroin use fully mediated the relationship between time since treatment
      initiation and needle-sharing. Women, patients who identified as being
      gay/lesbian/bisexual, those married or living with a partner and who reported
      heroin or alcohol use were more likely to report non-condom use. Older patients
      were less likely to report non-condom use. CONCLUSIONS: While
      buprenorphine/naloxone is associated with decreased needle-sharing among HIV
      infected opioid-dependent patients, sexual risk behaviors persist regardless of
      viral load. Targeted interventions to address HIV risk behaviors among HIV
      infected opioid-dependent populations receiving buprenorphine/naloxone are
      needed.

PMID- 24726431
TI  - SIRT1 inhibition restores apoptotic sensitivity in p53-mutated human
      keratinocytes.
AB  - Mutations to the p53 gene are common in UV-exposed keratinocytes and contribute
      to apoptotic resistance in skin cancer. P53-dependent activity is modulated, in
      part, by a complex, self-limiting feedback loop imposed by miR-34a-mediated
      regulation of the lysine deacetylase, SIRT1. Expression of numerous microRNAs is
      dysregulated in squamous and basal cell carcinomas; however the contribution of
      specific microRNAs to the pathogenesis of skin cancer remains untested. Through
      use of RNAi, miRNA target site blocking oligonucleotides and small molecule
      inhibitors, this study explored the influence of p53 mutational status, SIRT1
      activity and miR-34a levels on apoptotic sensitivity in primary (NHEK) and p53
      mutated (HaCaT) keratinocyte cell lines. SIRT1 and p53 are overexpressed in p53
      mutated keratinocytes, whilst miR-34a levels are 90% less in HaCaT cells. HaCaTs
      have impaired responses to p53/SIRT1/miR-34a axis manipulation which enhanced
      survival during exposure to the chemotherapeutic agent, camptothecin. Inhibition
      of SIRT1 activity in this cell line increased p53 acetylation and doubled
      camptothecin-induced cell death. Our results demonstrate that p53 mutations
      increase apoptotic resistance in keratinocytes by interfering with miR-34a
      mediated regulation of SIRT1 expression. Thus, SIRT1 inhibitors may have a
      therapeutic potential for overcoming apoptotic resistance during skin cancer
      treatment. 

PMID- 24726432
TI  - Relationships that compulsive buying has with addiction, obsessive
      compulsiveness, hoarding, and depression.
AB  - BACKGROUND AND OBJECTIVES: Compulsive buying has been associated with addiction,
      depression, and obsessive-compulsive disorder, as well as hoarding. The present
      study investigated the relationship that compulsive buying (CB) has with
      'addictive' (i.e., sensitivity to reward), obsessive-compulsive, and depressive
      phenomena, after controlling for hoarding, substance dependence, manic, and
      Borderline Personality Disorder symptoms. METHODS: 87 participants from a
      community population completed the online questionnaires for the study, however
      70 participants (M=29.19, SD=10.45; 70% were female) were used in the analyses
      because of exclusion criteria. RESULTS: As expected, CB measures correlated with
      hoarding, depression, sensitivity to reward, and, but less so, obsessive
      compulsive measures. Sensitivity to reward was the most important predictor of CB
      severity, compared to obsessive-compulsive and depression symptoms. Hoarding was
      also an important predictor of CB severity. LIMITATIONS: Small sample size meant
      gender comparisons could not be made, and the use of a novel, communicated
      questionnaire meant that interpretation should be considered conservatively.
      CONCLUSIONS: Overall, findings suggest that CB may be most closely related to the
      phenomena associated with addiction (an increased sensitivity to reward), rather
      than obsessive-compulsive or depression symptoms. Hoarding and reward sensitivity
      perhaps might separate compulsive buying from ordinary and recreational shopping.

PMID- 24726433
TI  - Water permeation drives tumor cell migration in confined microenvironments.
AB  - Cell migration is a critical process for diverse (patho)physiological phenomena.
      Intriguingly, cell migration through physically confined spaces can persist even
      when typical hallmarks of 2D planar migration, such as actin polymerization and
      myosin II-mediated contractility, are inhibited. Here, we present an integrated
      experimental and theoretical approach ("Osmotic Engine Model") and demonstrate
      that directed water permeation is a major mechanism of cell migration in confined
      microenvironments. Using microfluidic and imaging techniques along with
      mathematical modeling, we show that tumor cells confined in a narrow channel
      establish a polarized distribution of Na+/H+ pumps and aquaporins in the cell
      membrane, which creates a net inflow of water and ions at the cell leading edge
      and a net outflow of water and ions at the trailing edge, leading to net cell
      displacement. Collectively, this study presents an alternate mechanism of cell
      migration in confinement that depends on cell-volume regulation via water
      permeation.

PMID- 24726435
TI  - [Chronic meningoencephalitis with dementia].

PMID- 24726436
TI  - Progressive neuropsychiatric manifestations of phenylketonuria in adulthood.
AB  - INTRODUCTION: Neuropsychiatric signs and MRI abnormalities can occur in patients
      with phenylketonuria in adulthood. We describe clinical and radiological features
      of phenylketonuric patients and we discuss the advantage of continuing diet in
      adulthood. METHOD: We report late onset neuropsychiatric symptoms of four
      phenylketonuric patients (33-45years) diagnosed in infancy and report the case of
      a patient (33years) diagnosed with phenylketonuria because of late onset
      neurological signs. We describe clinical and radiological features of these 5
      patients, and their evolution under diet and propose a review of the literature.
      RESULTS: The main neurological abnormalities in phenylketonuric patients
      diagnosed in infancy are: brisk reflexes, spastic paraparesis, psychiatric signs
      that appear 10.5years after the diet arrest. A leukoencephalopathy was present in
      93% of cases and 91.7% improve clinically after poor phenylalanine diet
      reintroduction. In 4 patients, neurological abnormalities (spastic paraparesis,
      dementia, Parkinsonism) led to the late diagnosis. Two of them had a
      leukoencephalopathy on brain MRI. Patients had high levels of phenylalanine
      (above 1500MUmol/L) when neuropsychiatric signs occurred. Improvement after diet
      suggests that hyperphenylalaninemia has a direct toxic effect on the brain.
      DISCUSSION/CONCLUSION: The long-term follow-up of phenylketonuric patients is
      mandatory to depict and treat neurological complications in time. Diet
      reintroduction is efficacious in most cases.

PMID- 24726434
TI  - Reconstructing and reprogramming the tumor-propagating potential of glioblastoma
      stem-like cells.
AB  - Developmental fate decisions are dictated by master transcription factors (TFs)
      that interact with cis-regulatory elements to direct transcriptional programs.
      Certain malignant tumors may also depend on cellular hierarchies reminiscent of
      normal development but superimposed on underlying genetic aberrations. In
      glioblastoma (GBM), a subset of stem-like tumor-propagating cells (TPCs) appears
      to drive tumor progression and underlie therapeutic resistance yet remain poorly
      understood. Here, we identify a core set of neurodevelopmental TFs (POU3F2, SOX2,
      SALL2, and OLIG2) essential for GBM propagation. These TFs coordinately bind and
      activate TPC-specific regulatory elements and are sufficient to fully reprogram
      differentiated GBM cells to "induced" TPCs, recapitulating the epigenetic
      landscape and phenotype of native TPCs. We reconstruct a network model that
      highlights critical interactions and identifies candidate therapeutic targets for
      eliminating TPCs. Our study establishes the epigenetic basis of a developmental
      hierarchy in GBM, provides detailed insight into underlying gene regulatory
      programs, and suggests attendant therapeutic strategies. PAPERCLIP:

PMID- 24726437
TI  - Microbiological criteria for Campylobacter in broiler carcasses in Italy: a
      possible approach to derive them.
AB  - The aim of this paper was to provide suitable microbiological criteria (MC) for
      Campylobacter in broiler carcasses and a sampling plan to verify compliance with
      such criteria. Data were gathered in the presence and concentration of
      Campylobacter in broiler carcasses collected in three different Italian
      slaughterhouses, labelled as A, B and C. The sampling plan to be validated in
      each slaughterhouse included the analysis of three different carcasses collected
      immediately after chilling from 30 different lots, for a total of 90 samples per
      slaughterhouse. The number of positive samples containing above 100 CFU/g and
      above 1,000 CFU/g throughout the 30 tested lots was determined to estimate
      between-lot variability. Based on this information, the performance of four MC
      was evaluated for lot compliance: i) n=3; c=0; m=100 CFU/g; ii) n=3; c=0; m=1,000
      CFU/g; iii) n=3; c=1; m=1,000 CFU/g and iv) n=3; c=2; m=1,000 CFU/g. Positive
      Campylobacter samples were found in 60% of the lots tested in slaughterhouses A
      and C and in 73.3% of lots from slaughterhouse B. The differences among the three
      slaughterhouses in the mean Campylobacter levels found in positive samples were
      not significant and were used to evaluate the performance of the MC. The level of
      lot compliance to different MC was calculated and for the most stringent one
      (n=3; c=0; m=100 CFU/g) was 40% at slaughterhouses A and C but only 26.7% at
      slaughterhouse B. The results of this study show an alternative approach to
      establish MC for Campylobacter in broilers. According to (1) Campylobacter
      prevalence and concentration in Italy, (2) applied experimental plan and (3)
      selected slaughterhouses, the number of compliant lots to the suggested MC ranged
      between 26.7 and 100%. The selection of the fit for purpose MC is a risk manager
      decision, based on a reasonable balance between public health and cost for
      poultry industries.

PMID- 24726438
TI  - Follow-up of patients with early breast cancer: is it time to rewrite the story?
AB  - The guidelines for follow-up in breast cancer survivors support only performance
      of periodic physical examination and annual mammography. However, medical
      oncologists and primary care physicians routinely recommend both blood tests and
      non-mammographic imaging tests in asymptomatic patients, leading to an increased
      anxiety related to false-positive results and higher medical expenses. Recently,
      advanced imaging technologies have improved sensitivity/specificity to detect
      metastatic lesions before symptoms arise. Considering the progress made in the
      treatment of metastatic disease and the rapid evolution of targeted therapy, that
      requires customization of the strategy according to molecular characteristics of
      the disease, patients could derive real benefit to early detection of disease
      recurrence. This hypothesis must be tested in a prospective clinical trial. 

PMID- 24726439
TI  - Sarcopenia influences fall-related injuries in community-dwelling older adults.
AB  - This study aimed to determine the relationship between sarcopenia and fall
      related injuries in community-dwelling older adults in Korea. The study
      population comprised 2848 subjects aged 65 years or older who participated in the
      Korea National Health and Nutrition Examination Surveys during 2010-2011.
      Sarcopenia was considered to be present if the subject's appendicular skeletal
      muscle mass divided by his or her weight was less than 29.9% in men, or less than
      25.1% in women. The incidence of fall-related injuries during the past year among
      all the respondents was 4.3%, and the prevalence of sarcopenia was 32.2%. After
      controlling for sociodemographic variables and morbidity due to chronic diseases,
      the incidence of fall-related injuries remained significantly elevated among
      older adults with sarcopenia (odds ratio = 1.61, 95% confidence internal = 1.01
      2.54). Sarcopenia should be considered when investigating means of preventing of
      fall-related injuries in community-dwelling older adults. To prevent falls among
      these persons, it is vital to implement intervention programs that increase
      muscle mass. 

PMID- 24726440
TI  - Synthesis and biological evaluation of novel C6-cyclo secondary amine substituted
      purine steroid-nucleosides analogues.
AB  - Novel C6-cyclo secondary amine substituted purine steroid-nucleoside analogues (2
      9) were efficiently synthesized through displacement of the C6 chloro on the
      purine ring of series 1 with versatile cyclic secondary amines, including
      pyrrolidines, piperidine, morpholine, and piperazines. All the newly-synthesized
      compounds were evaluated for their anticancer activity in vitro against Hela, PC
      3 and MCF-7 cell lines. Among them, compounds 5c and 6b exhibited significant
      cytotoxicity on PC-3 cell lines. 

PMID- 24726441
TI  - A peripherally acting, selective T-type calcium channel blocker, ABT-639,
      effectively reduces nociceptive and neuropathic pain in rats.
AB  - Activation of T-type Ca2+ channels contributes to nociceptive signaling by
      facilitating action potential bursting and modulation of membrane potentials
      during periods of neuronal hyperexcitability. The role of T-type Ca2+ channels in
      chronic pain is supported by gene knockdown studies showing that decreased
      Ca(v)3.2 channel expression results in the loss of low voltage-activated (LVA)
      currents in dorsal root ganglion (DRG) neurons and attenuation of neuropathic
      pain in the chronic constriction injury (CCI) model. ABT-639 is a novel,
      peripherally acting, selective T-type Ca2+ channel blocker. ABT-639 blocks
      recombinant human T-type (Ca(v)3.2) Ca2+ channels in a voltage-dependent fashion
      (IC50 = 2 MUM) and attenuates LVA currents in rat DRG neurons (IC50 = 8 MUM). ABT
      639 was significantly less active at other Ca2+ channels (e.g. Ca(v)1.2 and
      Ca(v)2.2) (IC50 > 30 MUM). ABT-639 has high oral bioavailability (%F = 73), low
      protein binding (88.9%) and a low brain:plasma ratio (0.05:1) in rodents.
      Following oral administration ABT-639 produced dose-dependent antinociception in
      a rat model of knee joint pain (ED50 = 2 mg/kg, p.o.). ABT-639 (10-100 mg/kg,
      p.o.) also increased tactile allodynia thresholds in multiple models of
      neuropathic pain (e.g. spinal nerve ligation, CCI, and vincristine-induced).
      [corrected]. ABT-639 did not attenuate hyperalgesia in inflammatory pain models
      induced by complete Freund's adjuvant or carrageenan. At higher doses (e.g. 100
      300 mg/kg) ABT-639 did not significantly alter hemodynamic or psychomotor
      function. The antinociceptive profile of ABT-639 provides novel insights into the
      role of peripheral T-type (Ca(v)3.2) channels in chronic pain states.

PMID- 24726442
TI  - Protective role of amantadine in mitochondrial dysfunction and oxidative stress
      mediated by hepatitis C virus protein expression.
AB  - Amantadine is an antiviral and antiparkinsonian drug that has been evaluated in
      combination therapies against hepatitis C virus (HCV) infection. Controversial
      results have been reported concerning its efficacy, and its mechanism of action
      remains unclear. Data obtained in vitro suggested a role of amantadine in
      inhibiting HCV p7-mediated cation conductance. In keeping with the fact that
      mitochondria are responsible to ionic fluxes and that HCV infection impairs
      mitochondrial function, we investigated a potential role of amantadine in
      modulating mitochondrial function. Using a well-characterized inducible cell line
      expressing the full-length HCV polyprotein, we found that amantadine not only
      prevented but also rescued HCV protein-mediated mitochondrial dysfunction.
      Specifically, amantadine corrected (i) overload of mitochondrial Ca2+; (ii)
      inhibition of respiratory chain activity and oxidative phosphorylation; (iii)
      reduction of membrane potential; and (iv) overproduction of reactive oxygen
      species. The effects of amantadine were observed within 15 min following drug
      administration and confirmed in Huh-7.5 cells transfected with an infectious HCV
      genome. These effects were also observed in cells expressing subgenomic HCV
      constructs, indicating that they are not mediated or only in part mediated by p7.
      Single organelle analyzes carried out on isolated mouse liver mitochondria
      demonstrated that amantadine induces hyperpolarization of the membrane potential.
      Moreover, amantadine treatment increased the calcium threshold required to
      trigger mitochondrial permeability transition opening. In conclusion, these
      results support a role of amantadine in preserving cellular bioenergetics and
      redox homeostasis in HCV-infected cells and unveil an effect of the drug which
      might be exploited for a broader therapeutic utilization.

PMID- 24726443
TI  - Isoquercitrin and polyphosphate co-enhance mineralization of human osteoblast
      like SaOS-2 cells via separate activation of two RUNX2 cofactors AFT6 and Ets1.
AB  - Isoquercitrin, a dietary phytoestrogen, is a potential stimulator of bone
      mineralization used for prophylaxis of osteoporotic disorders. Here we studied
      the combined effects of isoquercitrin, a cell membrane permeable 3-O-glucoside of
      quercetin, and polyphosphate [polyP], a naturally occurring inorganic polymer
      inducing bone formation, on mineralization of human osteoblast-like SaOS-2 cells.
      Both compounds isoquercitrin and polyP induce at non-toxic concentrations the
      mineralization process of SaOS-2 cells. Co-incubation experiments revealed that
      isoquercitrin (at 0.1 and 0.3MUM), if given simultaneously with polyP (as Ca(2+)
      salt; at 3, 10, 30 and 100MUM) amplifies the mineralization-enhancing effect of
      the inorganic polymer. The biomineralization process induced by isoquercitrin and
      polyP is based on two different modes of action. After incubation of the cells
      with isoquercitrin or polyP the expression of the Runt-related transcription
      factor 2 [RUNX2] is significantly upregulated. In addition, isoquercitrin causes
      a strong increase of the steady-state-levels of the two co-activators of RUNX2,
      the activating transcription factor 6 [ATF6] and the Ets oncogene homolog 1
      [Ets1]. The activating effect of isoquercitrin occurs via a signal transduction
      pathway involving ATF6, and by that, is independent from the induction cascade
      initiated by polyP. This conclusion is supported by the finding that
      isoquercitrin upregulates the expression of the gene encoding for osteocalcin,
      while polyP strongly increases the expression of the Ets1 gene and of the
      alkaline phosphatase. We show that the two compounds, polyP and isoquercitrin,
      have a co-enhancing effect on bone mineral formation and in turn might be of
      potential therapeutic value for prevention/treatment of osteoporosis. 

PMID- 24726444
TI  - Stimulation of osteogenic and angiogenic ability of cells on polymers by pulsed
      laser deposition of uniform akermanite-glass nanolayer.
AB  - Polymer biomaterials have been widely used for bone replacement/regeneration
      because of their unique mechanical properties and workability. Their inherent low
      bioactivity makes them lack osseointegration with host bone tissue. For this
      reason, bioactive inorganic particles have been always incorporated into the
      matrix of polymers to improve their bioactivity. However, mixing inorganic
      particles with polymers always results in inhomogeneity of particle distribution
      in polymer matrix with limited bioactivity. This study sets out to apply the
      pulsed laser deposition (PLD) technique to prepare uniform akermanite
      (Ca2MgSi2O7, AKT) glass nanocoatings on the surface of two polymers (non
      degradable polysulfone (PSU) and degradable polylactic acid (PDLLA)) in order to
      improve their surface osteogenic and angiogenic activity. The results show that a
      uniform nanolayer composed of amorphous AKT particles (~30 nm) of thickness 130
      nm forms on the surface of both PSU and PDLLA films with the PLD technique. The
      prepared AKT-PSU and AKT-PDLLA films significantly improved the surface
      roughness, hydrophilicity, hardness and apatite mineralization, compared with
      pure PSU and PDLLA, respectively. The prepared AKT nanocoatings distinctively
      enhance the alkaline phosphate (ALP) activity and bone-related gene expression
      (ALP, OCN, OPN and Col I) of bone-forming cells on both PSU and PDLLA films.
      Furthermore, AKT nanocoatings on two polymers improve the attachment,
      proliferation, VEGF secretion and expression of proangiogenic factors and their
      receptors of human umbilical vein endothelial cells (HUVEC). The results suggest
      that PLD-prepared bioceramic nanocoatings are very useful for enhancing the
      physicochemical, osteogenic and angiogenic properties of both degradable and non
      degradable polymers for application in bone replacement/regeneration.

PMID- 24726445
TI  - Radiology in pioneer accountable care organizations: much ado about nothing?

PMID- 24726446
TI  - Radiation dose shift in relative proportion: the case of coronary artery calcium
      studies.

PMID- 24726447
TI  - Decision processes in temporal discrimination.
AB  - The processing dynamics underlying temporal decisions and the response times they
      generate have received little attention in the study of interval timing. In
      contrast, models of other simple forms of decision making have been extensively
      investigated using response times, leading to a substantial disconnect between
      temporal and non-temporal decision theories. An overarching decision-theoretic
      framework that encompasses existing, non-temporal decision models may, however,
      account both for interval timing itself and for time-based decision-making. We
      sought evidence for this framework in the temporal discrimination performance of
      humans tested on the temporal bisection task. In this task, participants
      retrospectively categorized experienced stimulus durations as short or long based
      on their perceived similarity to two, remembered reference durations and were
      rewarded only for correct categorization of these references. Our analysis of
      choice proportions and response times suggests that a two-stage, sequential
      diffusion process, parameterized to maximize earned rewards, can account for
      salient patterns of bisection performance. The first diffusion stage times
      intervals by accumulating an endogenously noisy clock signal; the second stage
      makes decisions about the first-stage temporal representation by accumulating
      first-stage evidence corrupted by endogenous noise. Reward-maximization requires
      that the second-stage accumulation rate and starting point be based on the state
      of the first-stage timer at the end of the stimulus duration, and that estimates
      of non-decision-related delays should decrease as a function of stimulus
      duration. Results are in accord with these predictions and thus support an
      extension of the drift-diffusion model of static decision making to the domain of
      interval timing and temporal decisions. 

PMID- 24726448
TI  - A mechanistic and structural investigation of modified derivatives of the
      diaryltriazine class of NNRTIs targeting HIV-1 reverse transcriptase.
AB  - BACKGROUND: Non-nucleoside reverse transcriptase inhibitors (NNRTIs) are vital in
      treating HIV-1 infection by inhibiting reverse transcriptase (RT). Drug toxicity
      and resistance drive the need for effective new inhibitors with improved
      physiochemical properties and potent antiviral activity. Computer-aided and
      structure-based drug design have guided the addition of solubilizing substituents
      to the diaryltriazine scaffold. These derivatives have markedly improved
      solubility and maintain low nanomolar antiviral activity against RT. The
      molecular and structural basis of inhibition for this series was determined to
      facilitate future inhibitor development with improved pharmacological profiles.
      METHODS: The molecular mechanism of inhibition was investigated using transient
      state kinetic analysis. Crystal structures of RT in complex with each inhibitor
      were obtained to investigate the structural basis of inhibition. RESULTS: The
      diaryltriazine and its morpholine derivative have RT inhibition constants of 9+/
      2nM and 14+/-4nM, respectively. They adopt differential binding modes within the
      non-nucleoside inhibitor binding pocket to distort the catalytic site geometry
      and primer grip regions. The novel morpholinopropoxy substituent extends into the
      RT/solvent interface of the NNIBP. CONCLUSIONS: Kinetic and structural analyses
      show that these inhibitors behave as conventional NNRTIs and inhibit the
      polymerization step. This study confirms that appending solubilizing substituents
      on the azine ring of diaryltriazine class of NNRTIs that extend into the
      RT/solvent interface effectively maintains low nanomolar potency and improves
      physiochemical properties. GENERAL SIGNIFICANCE: The modification of NNRTI
      scaffolds with solubilizing substituents, which extend into the RT/solvent
      interface, yields potent antivirals and is an effective strategy for developing
      novel inhibitors with improved pharmacological properties.

PMID- 24726449
TI  - Different activities of the conserved lysine residues in the double-stranded RNA
      binding domains of RNA helicase A in vitro and in the cell.
AB  - BACKGROUND: RNA helicase A regulates a variety of RNA metabolism processes
      including HIV-1 replication and contains two double-stranded RNA binding domains
      (dsRBD1 and dsRBD2) at the N-terminus. Each dsRBD contains two invariant lysine
      residues critical for the binding of isolated dsRBDs to RNA. However, the role of
      these conserved lysine residues was not tested in the context of enzymatically
      active full-length RNA helicase A either in vitro or in the cells. METHODS: The
      conserved lysine residues in each or both of dsRBDs were substituted by alanine
      in the context of full-length RNA helicase A. The mutant RNA helicase A was
      purified from mammalian cells. The effects of these mutations were assessed
      either in vitro upon RNA binding and unwinding or in the cell during HIV-1
      production upon RNA helicase A-RNA interaction and RNA helicase A-stimulated
      viral RNA processes. RESULTS: Unexpectedly, the substitution of the lysine
      residues by alanine in either or both of dsRBDs does not prevent purified full
      length RNA helicase A from binding and unwinding duplex RNA in vitro. However,
      these mutations efficiently inhibit RNA helicase A-stimulated HIV-1 RNA
      metabolism including the accumulation of viral mRNA and tRNA(Lys3) annealing to
      viral RNA. Furthermore, these mutations do not prevent RNA helicase A from
      binding to HIV-1 RNA in vitro as well, but dramatically reduce RNA helicase A-HIV
      1 RNA interaction in the cells. CONCLUSIONS: The conserved lysine residues of
      dsRBDs play critical roles in the promotion of HIV-1 production by RNA helicase
      A. GENERAL SIGNIFICANCE: The conserved lysine residues of dsRBDs are key to the
      interaction of RNA helicase A with substrate RNA in the cell, but not in vitro.

PMID- 24726450
TI  - Outcome of intracranial electroencephalography monitoring and surgery in magnetic
      resonance imaging-negative temporal lobe epilepsy.
AB  - We evaluated the outcomes of intracranial electroencephalography (iEEG) recording
      and subsequent resective surgery in patients with magnetic resonance imaging
      (MRI)-negative temporal lobe epilepsy (TLE). Thirty-two patients were identified
      from the Mayo Clinic Epilepsy Surgery Database (Arizona, Florida, and Minnesota).
      Eight (25.0%) had chronic iEEG monitoring that recorded neocortical temporal
      seizure onsets; 12 (37.5%) had mesial temporal seizure onsets; 5 (15.6%) had
      independent neocortical and mesial temporal seizure onsets; and 7 (21.9%) had
      simultaneous neocortical and mesial seizure onsets. Neocortical temporal lobe
      seizure semiology was the only factor significantly associated with neocortical
      temporal seizure onsets on iEEG. Only 33.3% of patients who underwent lateral
      temporal neocorticectomy had an Engel class 1 outcome, whereas 76.5% of patients
      with iEEG-guided anterior temporal lobectomy that included the amygdala and the
      hippocampus had an Engel class 1 outcome. Limitations in cohort size precluded
      statistical analysis of neuropsychological test data. 

PMID- 24726451
TI  - Structural changes in the temporal lobe and piriform cortex in frontal lobe
      epilepsy.
AB  - BACKGROUND: Neuronal networks involved in seizure generation, maintenance and
      spread of epileptic activity comprise cortico-subcortical circuits. Although
      epileptic foci vary in location across focal epilepsy syndromes, there is
      evidence for common structures in the epileptogenic networks. We recently
      reported evidence from functional neuroimaging for a unique area in the piriform
      cortex, common to focal epilepsies in humans, which might play a role in
      modulating seizure activity. In this study, we aimed to identify common areas of
      structural abnormalities in patients with frontal lobe epilepsy (FLE). METHODS:
      T1-weighted MRI scans of 43 FLE patients and 25 healthy controls were analysed
      using voxel based morphometry. Differences in regional grey matter volume were
      examined across the whole brain, and correlated with age at epilepsy onset,
      duration and frequency of seizures. RESULTS: We detected areas of increased grey
      matter volume in the piriform cortex, amygdala and parahippocampal gyrus
      bilaterally, as well as left mid temporal gyrus of patients relative to controls,
      which did not correlate with any of the clinical variables tested. No common
      areas of atrophy were detected across the FLE group. CONCLUSIONS: Structural
      abnormalities within the piriform cortex and adjacent structures of patients with
      FLE provide further evidence for the involvement of this area in the
      epileptogenic network of focal epilepsies. Lack of correlation with duration or
      age of onset of epilepsy suggests that this area of abnormality is not a
      consequence of seizure activity.

PMID- 24726452
TI  - Adjunctive use of ezogabine/retigabine with either traditional sodium channel
      blocking antiepileptic drugs (AEDs) or AEDs with other mechanisms of action:
      Evaluation of efficacy and tolerability.
AB  - Integrated data from three double-blind, randomized, placebo-controlled trials
      were analyzed to evaluate the efficacy and tolerability of ezogabine (EZG; US
      adopted name)/retigabine (RTG; international non-proprietary name) when used in
      combination with >=1 sodium channel blocking antiepileptic drug (AED), >=1 non
      sodium channel blocking AED, or >=1 AED from both the sodium channel and non
      sodium channel mechanistic groups. Efficacy and tolerability appeared to be
      similar across all three groups of patients. 

PMID- 24726453
TI  - Therapeutic applications of repetitive transcranial magnetic stimulation (rTMS)
      in movement disorders: a review.
AB  - Repetitive transcranial magnetic stimulation (rTMS) is emerging as a valuable
      adjunctive therapeutic modality in movement disorders. It is a non-invasive
      technique of repeated stimulation of the cerebral cortex by a train of magnetic
      pulses. The therapeutic effect of rTMS was first noted in depression. Later
      several researchers have investigated the role of rTMS in various movement
      disorders, notably Parkinson's disease, dystonia, Tourette's syndrome etc. The
      rTMS protocols used in these studies vary widely, lacks uniformity and often the
      results are not consistent. The optimal rTMS parameters for each disorder are yet
      to be established. This review discusses the current knowledge on the therapeutic
      applications of rTMS in various movement disorders. 

PMID- 24726454
TI  - Utility and limitations of T. gondii-specific IgM serum antibodies in the
      diagnosis of congenital toxoplasmosis in Porto Alegre.

PMID- 24726455
TI  - Evaluation of the medication process in pediatric patients: a meta-analysis.
AB  - OBJECTIVE: to meta-analyze studies that have assessed the medication errors rate
      in pediatric patients during prescribing, dispensing, and drug administration.
      SOURCES: searches were performed in the PubMed, Cochrane Library, and Trip
      databases, selecting articles published in English from 2001 to 2010. SUMMARY OF
      THE FINDINGS: a total of 25 original studies that met inclusion criteria were
      selected, which referred to pediatric inpatients or pediatric patients in
      emergency departments aged 0-16 years, and assessed the frequency of medication
      errors in the stages of prescribing, dispensing, and drug administration.
      CONCLUSIONS: the combined medication error rate for prescribing errors to
      medication orders was 0.175 (95% Confidence Interval: [CI] 0.108-0.270), the rate
      of prescribing errors to total medication errors was 0.342 (95% CI: 0.146-0.611),
      that of dispensing errors to total medication errors was 0.065 (95% CI: 0.026
      0.154), and that ofadministration errors to total medication errors was 0.316
      (95% CI: 0.148-0.550). Furthermore, the combined medication error rate for
      administration errors to drug administrations was 0.209 (95% CI: 0.152-0.281).
      Medication errors constitute a reality in healthcare services. The medication
      process is significantly prone to errors, especially during prescription and drug
      administration. Implementation of medication error reduction strategies is
      required in order to increase the safety and quality of pediatric healthcare.

PMID- 24726457
TI  - Shaping science policy in Europe.
AB  - The Lisbon Strategy was adopted by the Heads of State and Government of the
      European Union (EU) in 2000. By moving science into a central position for the
      development of a European knowledge-based economy and society, its adoption at
      political level seems to have been a powerful catalyst for the increased
      involvement of scientists in science policy in the EU. Recognising the need for
      scientists to act collectively in order to contribute to shape the future of
      science policy in Europe, a pioneering group of European science organisations
      leaders and representatives, as well as other scientists, initiated a European,
      interdisciplinary, inclusive movement leading to the creation of the European
      Research Council (ERC) to support basic research of the highest quality. Having
      scientists' campaign for the funding of bottom-up research by the EU Framework
      Programmes exclusively on scientific grounds, and for an ERC, was a unique event
      in the recent history of European science policy. For the first time, the
      scientific community acted collectively and across disciplinary or national
      boundaries as a political actor for the sake of a better science policy for
      Europe. As is often the case when first-hand experience is gained through the
      creation of a new organization, novel forms of collaboration arise. The European
      biomedical community has recently proposed the creation of a strategic action
      plan for health research (the European Council of Health Research; EuCHR),
      provisionally translated at present into a Scientific Panel for Health (SPH)
      research in Horizon 2020, the EU's research-funding programme for the period 2014
      2020. The creation of such Scientific Panel should be viewed as an important
      contribution by the biomedical community as a major political agreement has been
      reached on the need for a comprehensive and long-term scientific strategy to
      accelerate research and facilitate innovation at EU level. It is our belief that
      describing and analyzing the process leading to the creation of the ERC and SPH
      (2002-2014) should be widely shared with the research community in general, as
      this may contribute to the understanding of the evolving relations between
      scientists and science-policy making. 

PMID- 24726456
TI  - Suppressor of cytokine signaling 1 modulates invasion and metastatic potential of
      colorectal cancer cells.
AB  - Suppressor of cytokine signaling (SOCS) 1 is an inducible negative regulator of
      cytokine signaling but its role in human cancer is not completely established.
      Here we report that, while SOCS1 is expressed in normal colonic epithelium and
      colon adenocarcinomas, its level decreases during progression of colon
      adenocarcinomas, the lowest level being found in the most aggressive stage and
      least differentiated carcinomas. Forced expression of SOCS1 in metastatic
      colorectal SW620 cells reverses many characteristics of Epithelial-Mesenchymal
      Transition (EMT), as highlighted by the disappearance of the transcription factor
      ZEB1 and the mesenchymal form of p120ctn and the re-expression of E-cadherin.
      Furthermore, miRNA profiling indicated that SOCS1 also up-regulates the
      expression of the mir-200 family of miRNAs, which can promote the mesenchymal
      epithelial transition and reduce tumor cell migration. Accordingly,
      overexpression of SOCS1 induced cell morphology changes and dramatically reduced
      tumor cell invasion in vitro. When injected in nude mice, SOCS1-expressing SW620
      cells induced metastases in a smaller number of animals than parental SW620
      cells, and did not generate any adrenal gland or bone metastasis. Overall, our
      results suggest that SOCS1 controls metastatic progression of colorectal tumors
      by preventing the mesenchymal-epithelial transition (MET), including E-cadherin
      expression. This pathway may be associated with survival to colorectal cancer by
      reducing the capacity of generating metastases.

PMID- 24726459
TI  - Comparison of margins, integral dose and interfraction target coverage with image
      guided radiotherapy compared with non-image-guided radiotherapy for bladder
      cancer.
AB  - AIMS: To measure the difference in cumulative doses received by the bladder
      (target) and integral doses with different clinical target volume (CTV) to
      planning target volume (PTV) margins, comparing set-up to skin tattoos versus
      image-guided radiotherapy to bone or soft tissue. MATERIALS AND METHODS: Four
      plans were generated on each planning computed tomography dataset using the CTV
      with 5, 10, 15, 20 mm PTV margins using a three-dimensional conformal four-field
      technique. Set-up data based on skin, bone and soft tissue to the bladder on pre
      treatment cone beam computed tomography (CBCT) were recorded. In total, 316 CBCTs
      were evaluable from 10 bladder cancer patients. Each CBCT was fused to the
      planning computed tomography dataset using the isocentre corresponding to each of
      the three pre-treatment matching conditions. The target was contoured on each
      CBCT and called the CTV of the day and the plan was re-calculated to determine
      the dose to this. RESULTS: The mean D95 with CTV to PTV margins of 5, 10, 15 and
      20 mm for skin set-up was 89.4, 93.0, 97.2, 98.6; for bone 88.8, 92.6, 96.7,
      98.6; and for soft tissue 96.3, 98.6, 98.7, 99.5. With soft-tissue matching, the
      mean (standard deviation) volume of normal tissue receiving 5 Gy with 5, 10, 15
      and 20 mm margins was 3899 (1022), 4561 (1142), 5663 (1304) and 6315 (1426) in
      cm(3). CONCLUSION: Soft-tissue matching results in superior target coverage and a
      reduced integral dose to the surrounding tissues. With soft-tissue matching,
      increasing CTV to PTV margins progressively beyond 5 mm results in modest
      improvement in CTV coverage, but a large increase in integral dose.

PMID- 24726460
TI  - Targeting receptor-activator of nuclear kappaB ligand in aneurysmal bone cysts:
      verification of target and therapeutic response.
AB  - Aneurysmal bone cyst (ABC) is a benign tumor of bone presenting as a cystic,
      expansile lesion in both the axial and appendicular skeleton. Axial lesions
      demand special consideration, because treatment-related morbidity can be
      devastating. In similar lesions, such as giant cell tumor of bone (GCTB), the
      receptor-activator of nuclear kappaB ligand (RANKL)-receptor-activator of nuclear
      kappaB (RANK) signaling axis is essential to tumor progression. Although ABC and
      GCTB are distinct entities, they both contain abundant multinucleated giant cells
      and are osteolytic characteristically. We hypothesize that ABCs express both
      RANKL and RANK similarly in a cell-type specific manner, and that targeted RANKL
      therapy will mitigate ABC tumor progression. Cellular expression of RANKL and
      RANK was determined in freshly harvested ABC samples using laser confocal
      microscopy. A consistent cell-type-specific pattern was observed: fibroblastlike
      stromal cells expressed RANKL strongly whereas monocyte/macrophage precursor and
      multinucleated giant cells expressed RANK. Relative RANKL expression was
      determined by quantitative real-time polymerase chain reaction in ABC and GCTB
      tissue samples; no difference in relative expression was observed (P > 0.05). In
      addition, we review the case of a 5-year-old boy with a large, aggressive sacral
      ABC. After 3 months of targeted RANKL inhibition with denosumab, magnetic
      resonance imaging demonstrated tumor shrinkage, bone reconstitution, and healing
      of a pathologic fracture. Ambulation, and bowel and bladder function were
      restored at 6 months. Denosumab treatment was well tolerated. Post hoc analysis
      demonstrated strong RANKL expression in the pretreatment tumor sample. These
      findings demonstrate that RANKL-RANK signal activation is essential to ABC tumor
      progression. RANKL-targeted therapy may be an effective alternative to surgery in
      select ABC presentations.

PMID- 24726458
TI  - Identification of novel non-coding RNA-based negative feedback regulating the
      expression of the oncogenic transcription factor GLI1.
AB  - Non-coding RNAs are a complex class of nucleic acids, with growing evidence
      supporting regulatory roles in gene expression. Here we identify a non-coding RNA
      located head-to-head with the gene encoding the Glioma-associated oncogene 1
      (GLI1), a transcriptional effector of multiple cancer-associated signaling
      pathways. The expression of this three-exon GLI1 antisense (GLI1AS) RNA in cancer
      cells was concordant with GLI1 levels. siRNAs knockdown of GLI1AS up-regulated
      GLI1 and increased cellular proliferation and tumor growth in a xenograft model
      system. Conversely, GLI1AS overexpression decreased the levels of GLI1, its
      target genes PTCH1 and PTCH2, and cellular proliferation. Additionally, we
      demonstrate that GLI1 knockdown reduced GLI1AS, while GLI1 overexpression
      increased GLI1AS, supporting the role of GLI1AS as a target gene of the GLI1
      transcription factor. Activation of TGFbeta and Hedgehog signaling, two known
      regulators of GLI1 expression, conferred a concordant up-regulation of GLI1 and
      GLI1AS in cancer cells. Finally, analysis of the mechanism underlying the
      interplay between GLI1 and GLI1AS indicates that the non-coding RNA elicits a
      local alteration of chromatin structure by increasing the silencing mark H3K27me3
      and decreasing the recruitment of RNA polymerase II to this locus. Taken
      together, the data demonstrate the existence of a novel non-coding RNA-based
      negative feedback loop controlling GLI1 levels, thus expanding the repertoire of
      mechanisms regulating the expression of this oncogenic transcription factor.

PMID- 24726461
TI  - The relationship between obesity and coronary artery disease.
AB  - Obesity continues to be a growing issue in the United States, with an estimated
      prevalence of 72 million people. There are major health implications associated
      with obesity, including its relationship with hypertension, diabetes mellitus
      type 2, metabolic syndrome, and dyslipidemia, all independent risk factors for
      coronary artery disease (CAD). Despite the increased risk of developing CAD, in
      recent years an "obesity paradox" has been described in which moderately obese
      individuals with established cardiovascular disease, including CAD, appear to
      have mortality similar to their normal-weight counterparts. This review examines
      the relationship between obesity and CAD, including the increased risk of
      hypertension, diabetes mellitus, metabolic syndrome, and dyslipidemia, along with
      a discussion of the obesity paradox and the benefits of weight reduction.

PMID- 24726462
TI  - The racial and ethnic gap in substance use treatment: implications for U.S.
      healthcare reform.

PMID- 24726463
TI  - Differentiating youth who are bullied from other victims of peer-aggression: the
      importance of differential power and repetition.
AB  - PURPOSE: To examine whether (1) among youth who report being bullied,
      differential power and repetition are useful in identifying youth who are more or
      less affected by the victimization experience and (2) bullying and more
      generalized peer aggression are distinct or overlapping constructs. METHODS: Data
      for the Teen Health and Technology study were collected online between August
      2010 and January 2011 from 3,989 13- to 18-year-olds. Data from the Growing up
      with Media study (Wave 3) were collected online in 2008 from 1,157 12- to 17-year
      olds. RESULTS: In the Teen Health and Technology study, youth who reported
      neither differential power nor repetition had the lowest rates of interference
      with daily functioning. Youth who reported either differential power or
      repetition had higher rates, but the highest rates of interference with daily
      functioning were observed among youth who reported both differential power and
      repetition. In the Growing up with Media study, youth were victims of online
      generalized peer aggression (30%) or both online generalized peer aggression and
      cyberbullying (16%) but rarely cyberbullying alone (1%). CONCLUSIONS: Both
      differential power and repetition are key in identifying youth who are bullied
      and at particular risk for concurrent psychosocial challenge. Each feature needs
      to be measured directly. Generalized peer aggression appears to be a broader form
      of violence compared with bullying. It needs to be recognized that youth who are
      victimized but do not meet the criteria of bullying have elevated rates of
      problems. They are an important, albeit nonbullied, group of victimized youth to
      be included in research.

PMID- 24726464
TI  - SAPHO syndrome in an adolescent: a clinical case with unusual severe systemic
      impact.
AB  - SAPHO (synovitis, acne, pustulosis, hyperostosis, and osteitis) syndrome includes
      both dermatological and rheumatologic symptoms. Being a rare condition, the
      diagnosis is frequently late. The authors report a case of a 13-year-old boy
      diagnosed with synovitis, acne, pustulosis, hyperostosis, and osteitis syndrome
      with unusual severe systemic repercussions. The patient presented with acne
      conglobata, inability to walk due to pain and weakness and weight loss. Bone
      scintigraphy was suggestive of sacroiliitis, and lumbar spine x-ray showed signs
      of hyperostosis. His clinical state improved after treatment with nonsteroidal
      anti-inflammatory drugs, methotrexate, clindamycin, and isotretinoin. A review of
      the clinical aspects of this syndrome is presented, emphasizing how this
      underdiagnosed syndrome can lead to severe weight loss and significant functional
      and psychological impairment at an early age. 

PMID- 24726465
TI  - Estradiol enhances object recognition memory in Swiss female mice by activating
      hippocampal estrogen receptor alpha.
AB  - In rodents, 17beta-estradiol (E2) enhances hippocampal function and improves
      performance in several memory tasks. Regarding the object recognition paradigm,
      E2 commonly act as a cognitive enhancer. However, the types of estrogen receptor
      (ER) involved, as well as the underlying molecular mechanisms are still under
      investigation. In the present study, we asked whether E2 enhances object
      recognition memory by activating ERalpha and/or ERbeta in the hippocampus of
      Swiss female mice. First, we showed that immediately post-training
      intraperitoneal (i.p.) injection of E2 (0.2 mg/kg) allowed object recognition
      memory to persist 48 h in ovariectomized (OVX) Swiss female mice. This result
      indicates that Swiss female mice are sensitive to the promnesic effects of E2 and
      is in accordance with other studies, which used C57/BL6 female mice. To verify if
      the activation of hippocampal ERalpha or ERbeta would be sufficient to improve
      object memory, we used PPT and DPN, which are selective ERalpha and ERbeta
      agonists, respectively. We found that PPT, but not DPN, improved object memory in
      Swiss female mice. However, DPN was able to improve memory in C57/BL6 female
      mice, which is in accordance with other studies. Next, we tested if the E2 effect
      on improving object memory depends on ER activation in the hippocampus. Thus, we
      tested if the infusion of intra-hippocampal TPBM and PHTPP, selective antagonists
      of ERalpha and ERbeta, respectively, would block the memory enhancement effect of
      E2. Our results showed that TPBM, but not PHTPP, blunted the promnesic effect of
      E2, strongly suggesting that in Swiss female mice, the ERalpha and not the ERbeta
      is the receptor involved in the promnesic effect of E2. It was already
      demonstrated that E2, as well as PPT and DPN, increase the phospho-ERK2 level in
      the dorsal hippocampus of C57/BL6 mice. Here we observed that PPT increased
      phospho-ERK1, while DPN decreased phospho-ERK2 in the dorsal hippocampus of Swiss
      female mice subjected to the object recognition sample phase. Taken together, our
      results suggest that the type of receptor as well as the molecular mechanism used
      by E2 to improve object memory may differ in Swiss female mice.

PMID- 24726466
TI  - Forest pit viper (Bothriopsis bilineata bilineata) bite in the Brazilian Amazon
      with acute kidney injury and persistent thrombocytopenia.
AB  - There are six species of Bothriopsis in Latin America, accidents caused by this
      genus are unusually reported. A 37-year-old man admitted thirty hours after a
      snakebite to the emergency department of Santarem City Hospital (SCH), northern
      Brazil. The patient presented local erythema, edema, increased local temperature
      and blister with serous fluid in the right arm. He developed acute kidney injury
      (AKI) and prolonged thrombocytopenia. The blood was incoagulable and he was
      treated with anti-bothropic antivenom and antibiotics. The patient had complete
      regression of all clinical and laboratory manifestations at varying intervals.
      The platelet counts returned to normal almost 2 weeks after administration of
      specific antivenom. The present report is the first accident caused by a snake of
      forest pit viper (Bothriopsis bilineata) in the Brazilian Amazon forest.

PMID- 24726467
TI  - The Australian mulga snake (Pseudechis australis: Elapidae): report of a large
      case series of bites and review of current knowledge.
AB  - BACKGROUND: The mulga snake (Pseudechis australis) is the largest terrestrial
      venomous snake in Australia. It is capable of inflicting severe and occasionally
      fatal envenoming, but there have been few studies of P. australis bites.
      OBJECTIVES: To highlight and reinforce the main features of P. australis
      envenoming and to provide a clearer picture of the epidemiology of bites from
      this species. METHODS: Selected case records kept by the Toxinology Dept.
      (Women's and Children's Hospital, Adelaide, Australia) were reviewed
      retrospectively to determine definite P. australis bites. INCLUSION CRITERIA:
      definite cases where the snake was identified by a competent person and/or lab
      specimens (bite site/urine) tested positive for "black snake" using CSL snake
      venom detection kit in a locality within the known range of P. australis, but
      without sympatry with other Pseudechis spp. EXCLUSION CRITERIA: where the snake
      could not be clearly identified under criteria above. Epidemiological and
      clinical information was recorded and analysed for the definite cases. RESULTS: A
      total of 27 cases were identified as definite P. australis bites; there were no
      fatalities. The median age was 35.5 years (IQR 51-23) and 80% of bites occurred
      in males. More bites occurred in the warmer months (Dec-March) and in those
      handling/interfering with snakes. Seven people were bitten whilst asleep at
      night. 21/27 patients developed systemic envenoming (based on signs, symptoms and
      laboratory results) and 17 cases received antivenom. Local bite site pain (18)
      and swelling (17) were common as were non-specific generalised symptoms such as
      nausea, vomiting and headache. Myotoxicity (11) and anticoagulant coagulopathy
      (10) occurred frequently; haemolysis was seen in fewer cases (3). Two patients
      developed local tissue injury around the bite site requiring further treatment.
      CONCLUSIONS: This study confirms previous reports about P. australis bites with
      respect to high rates of envenoming, commonly associated with pain and swelling
      and systemic effects of rhabdomyolysis and anticoagulant coagulopathy. Systemic
      envenoming, even severe cases, responds well to antivenom therapy. Compared to
      other Australian snakes, a high proportion of bites occur in people asleep at
      night. Medically significant local tissue injury around the bite site may occur
      and may be associated with inappropriate first-aid, particularly the vascular
      occlusive type.

PMID- 24726468
TI  - Whole venom of Loxosceles similis activates caspases-3, -6, -7, and -9 in human
      primary skin fibroblasts.
AB  - Spiders of the Loxosceles genus represent a risk to human health due to the
      systemic and necrotic effects of their bites. The main symptoms of these bites
      vary from dermonecrosis, observed in the majority of cases, to occasional
      systemic hemolysis and coagulopathy. Although the systemic effects are well
      characterized, the mechanisms of cell death triggered by the venom of these
      spiders are poorly characterized. In this study, we investigated the cell death
      mechanisms induced by the whole venom of the spider Loxosceles similis in human
      skin fibroblasts. Our results show that the venom initiates an apoptotic process
      and a caspase cascade involving the initiator caspase-9 and the effector caspases
      3, -6, and -7. 

PMID- 24726469
TI  - Verified spider bites in Oregon (USA) with the intent to assess hobo spider venom
      toxicity.
AB  - This study compiled 33 verified spider bites from the state of Oregon (USA). The
      initial goal was to amass a series of bites by the hobo spider to assess whether
      it possesses toxic venom, a supposition which is currently in a contested state.
      None of the 33 bites from several spider species developed significant medical
      symptoms nor did dermonecrosis occur. The most common biters were the yellow sac
      spider, Cheiracanthium mildei (N = 10) and orb-weavers of the genus Araneus (N =
      6). There were 10 bites from three genera of funnel web spiders of the family
      Agelenidae including one hobo spider bite and one from the congeneric giant house
      spider which is readily confused as a hobo spider. The hobo spider bite resulted
      in pain, redness, twitching in the calf muscle and resolved in 12 h. Also
      generated from this study were possibly the first records of bites from spiders
      of the genera Callobius (Amaurobiidae) and Antrodiaetus (Antrodiaetidae), both
      with minor manifestations. 

PMID- 24726470
TI  - Pituitary adenylate cyclase-activating polypeptide protects against beta-amyloid
      toxicity.
AB  - Pituitary adenylate cyclase activating polypeptide (PACAP) is a neurotrophin.
      However, its role in human Alzheimer's disease (AD) is largely unknown. We
      examined PACAP expression in postmortem human AD and triple transgenic mouse
      (3xTG, Psen1/APPSwe/TauP301L) brains. We established an in vitro model of primary
      neuronal cell culture to study the protective effects of PACAP against beta
      amyloid (Abeta) toxicity. We further studied the PACAP-Sirtuin 3 (Sirt3) pathway
      on mitochondrial function. PACAP expression was reduced in AD and 3xTG mouse
      brains. This reduction was inversely correlated with Abeta and tau protein
      levels. Treatment with PACAP effectively protected neurons against Abeta
      toxicity. PACAP stimulated mitochondrial Sirt3 production. Similar to PACAP,
      Sirt3 was reduced in AD and 3xTG brains. Knocking down Sirt3 compromised the
      neuroprotective effects of PACAP, and this was reversed by over-expressing Sirt3.
      PACAP is reduced in AD and may represent a novel therapeutic strategy.

PMID- 24726471
TI  - Raloxifene activates G protein-coupled estrogen receptor 1/Akt signaling to
      protect dopamine neurons in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine mice.
AB  - Raloxifene, used in the clinic, is reported to protect brain dopaminergic neurons
      in mice. Raloxifene was shown to mediate an effect through the G protein-coupled
      estrogen receptor 1 (GPER1). We investigated if raloxifene neuroprotective effect
      in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated male mice is
      mediated through GPER1 by using its antagonist G15. Striatal concentrations of
      dopamine, 3,4-dihydroxyphenylacetic acid, homovanillic acid to dopamine ratio as
      well as dopamine transporter and vesicular monoamine transporter 2 showed that
      raloxifene neuroprotection of dopaminergic neurons was blocked by G15. Protection
      by raloxifene was accompanied by activation of striatal Akt signaling (but not
      ERK1/2 signaling) and increased Bcl-2 and brain-derived neurotrophic factor
      levels; these effects were abolished by coadministration with G15. The effect of
      raloxifene was not mediated through increased levels of 17beta-estradiol. MPTP
      mice had decreased plasma testosterone, dihydrotestosterone, and 3beta-diol
      levels; this was prevented in raloxifene-treated MPTP mice. Our results suggest
      that raloxifene acted through GPER1 to mediate Akt activation, increase Bcl-2 and
      brain-derived neurotrophic factor levels, and protection of dopaminergic neurons
      and plasma androgens. 

PMID- 24726472
TI  - Mutations affecting the SAND domain of DEAF1 cause intellectual disability with
      severe speech impairment and behavioral problems.
AB  - Recently, we identified in two individuals with intellectual disability (ID)
      different de novo mutations in DEAF1, which encodes a transcription factor with
      an important role in embryonic development. To ascertain whether these mutations
      in DEAF1 are causative for the ID phenotype, we performed targeted resequencing
      of DEAF1 in an additional cohort of over 2,300 individuals with unexplained ID
      and identified two additional individuals with de novo mutations in this gene.
      All four individuals had severe ID with severely affected speech development, and
      three showed severe behavioral problems. DEAF1 is highly expressed in the CNS,
      especially during early embryonic development. All four mutations were missense
      mutations affecting the SAND domain of DEAF1. Altered DEAF1 harboring any of the
      four amino acid changes showed impaired transcriptional regulation of the DEAF1
      promoter. Moreover, behavioral studies in mice with a conditional knockout of
      Deaf1 in the brain showed memory deficits and increased anxiety-like behavior.
      Our results demonstrate that mutations in DEAF1 cause ID and behavioral problems,
      most likely as a result of impaired transcriptional regulation by DEAF1. 

PMID- 24726473
TI  - Mutations in PIEZO2 cause Gordon syndrome, Marden-Walker syndrome, and distal
      arthrogryposis type 5.
AB  - Gordon syndrome (GS), or distal arthrogryposis type 3, is a rare, autosomal
      dominant disorder characterized by cleft palate and congenital contractures of
      the hands and feet. Exome sequencing of five GS-affected families identified
      mutations in piezo-type mechanosensitive ion channel component 2 (PIEZO2) in each
      family. Sanger sequencing revealed PIEZO2 mutations in five of seven additional
      families studied (for a total of 10/12 [83%] individuals), and nine families had
      an identical c.8057G>A (p.Arg2686His) mutation. The phenotype of GS overlaps with
      distal arthrogryposis type 5 (DA5) and Marden-Walker syndrome (MWS). Using
      molecular inversion probes for targeted sequencing to screen PIEZO2, we found
      mutations in 24/29 (82%) DA5-affected families and one of two MWS-affected
      families. The presence of cleft palate was significantly associated with
      c.8057G>A (Fisher's exact test, adjusted p value < 0.0001). Collectively,
      although GS, DA5, and MWS have traditionally been considered separate disorders,
      our findings indicate that they are etiologically related and perhaps represent
      variable expressivity of the same condition. 

PMID- 24726475
TI  - Hanging by threads: ectopia lentis.

PMID- 24726476
TI  - Tissue engineering's green shoots of disruptive innovation.

PMID- 24726477
TI  - Engineered autologous cartilage tissue for nasal reconstruction after tumour
      resection: an observational first-in-human trial.
AB  - BACKGROUND: Autologous native cartilage from the nasal septum, ear, or rib is the
      standard material for surgical reconstruction of the nasal alar lobule after two
      layer excision of non-melanoma skin cancer. We assessed whether engineered
      autologous cartilage grafts allow safe and functional alar lobule restoration.
      METHODS: In a first-in-human trial, we recruited five patients at the University
      Hospital Basel (Basel, Switzerland). To be eligible, patients had to be aged at
      least 18 years and have a two-layer defect (>=50% size of alar subunit) after
      excision of non-melanoma skin cancer on the alar lobule. Chondrocytes (isolated
      from a 6 mm cartilage biopsy sample from the nasal septum harvested under local
      anaesthesia during collection of tumour biopsy sample) were expanded, seeded, and
      cultured with autologous serum onto collagen type I and type III membranes in the
      course of 4 weeks. The resulting engineered cartilage grafts (25 mm * 25 mm * 2
      mm) were shaped intra-operatively and implanted after tumour excision under
      paramedian forehead or nasolabial flaps, as in standard reconstruction with
      native cartilage. During flap refinement after 6 months, we took biopsy samples
      of repair tissues and histologically analysed them. The primary outcomes were
      safety and feasibility of the procedure, assessed 12 months after reconstruction.
      At least 1 year after implantation, when reconstruction is typically stabilised,
      we assessed patient satisfaction and functional outcomes (alar cutaneous
      sensibility, structural stability, and respiratory flow rate). FINDINGS: Between
      Dec 13, 2010, and Feb 6, 2012, we enrolled two women and three men aged 76-88
      years. All engineered grafts contained a mixed hyaline and fibrous cartilage
      matrix. 6 months after implantation, reconstructed tissues displayed
      fibromuscular fatty structures typical of the alar lobule. After 1 year, all
      patients were satisfied with the aesthetic and functional outcomes and no adverse
      events had been recorded. Cutaneous sensibility and structural stability of the
      reconstructed area were clinically satisfactory, with adequate respiratory
      function. INTERPRETATION: Autologous nasal cartilage tissues can be engineered
      and clinically used for functional restoration of alar lobules. Engineered
      cartilage should now be assessed for other challenging facial reconstructions.
      FUNDING: Foundation of the Department of Surgery, University Hospital Basel; and
      Krebsliga beider Basel.

PMID- 24726478
TI  - Tissue-engineered autologous vaginal organs in patients: a pilot cohort study.
AB  - BACKGROUND: Several disorders might require vaginal reconstruction, such as
      congenital abnormalities, injury, or cancer. Reconstructive techniques for which
      non-vaginal tissue is used can be associated with complications. We assessed the
      use of engineered vaginal organs in four patients with vaginal aplasia caused by
      Mayer-Rokitansky-Kuster-Hauser syndrome (MRKHS). METHODS: We invited to
      participate four consecutive patients who presented over a 3-year period with
      congenital vaginal aplasia due to MRKHS. Patients were aged 13-18 years. We
      obtained a vulvar biopsy of autologous tissue from every patient. We cultured,
      expanded, and seeded epithelial and muscle cells onto biodegradable scaffolds.
      The organs were constructed and allowed to mature in an incubator in a facility
      approved for human-tissue manufacturing. We used a perineal approach to
      surgically implant these organs. We recorded history, physical examination,
      vaginoscopy, serial tissue biopsies, MRIs, and self-administered Female Sexual
      Function Index questionnaire results for all patients, with a follow-up of up to
      8 years. FINDINGS: We noted no long-term postoperative surgical complications.
      Yearly serial biopsies showed a tri-layered structure, consisting of an
      epithelial cell-lined lumen surrounded by matrix and muscle, with expected
      components of vaginal tissue present. Immunohistochemical analysis confirmed the
      presence of phenotypically normal smooth muscle and epithelia. The MRIs, which
      showed the extent of the vaginal aplasia before surgery, showed the engineered
      organs and the absence of abnormalities after surgery, which was confirmed with
      yearly vaginoscopy. A validated self-administered Female Sexual Function Index
      questionnaire showed variables in the normal range in all areas tested, such as
      desire, arousal, lubrication, orgasm, satisfaction, and painless intercourse.
      INTERPRETATION: Vaginal organs, engineered from the patient's own cells and
      implanted, showed normal structural and functional variables with a follow-up of
      up to 8 years. These technologies could be useful in patients requiring vaginal
      reconstruction. FUNDING: Wake Forest University and Hospital Infantil de Mexico
      Federico Gomez.

PMID- 24726474
TI  - Maternal history of Oceania from complete mtDNA genomes: contrasting ancient
      diversity with recent homogenization due to the Austronesian expansion.
AB  - Archaeology, linguistics, and existing genetic studies indicate that Oceania was
      settled by two major waves of migration. The first migration took place
      approximately 40 thousand years ago and these migrants, Papuans, colonized much
      of Near Oceania. Approximately 3.5 thousand years ago, a second expansion of
      Austronesian-speakers arrived in Near Oceania and the descendants of these people
      spread to the far corners of the Pacific, colonizing Remote Oceania. To assess
      the female contribution of these two human expansions to modern populations and
      to investigate the potential impact of other migrations, we obtained 1,331 whole
      mitochondrial genome sequences from 34 populations spanning both Near and Remote
      Oceania. Our results quantify the magnitude of the Austronesian expansion and
      demonstrate the homogenizing effect of this expansion on almost all studied
      populations. With regards to Papuan influence, autochthonous haplogroups support
      the hypothesis of a long history in Near Oceania, with some lineages suggesting a
      time depth of 60 thousand years, and offer insight into historical
      interpopulation dynamics. Santa Cruz, a population located in Remote Oceania, is
      an anomaly with extreme frequencies of autochthonous haplogroups of Near Oceanian
      origin; simulations to investigate whether this might reflect a pre-Austronesian
      versus Austronesian settlement of the island failed to provide unequivocal
      support for either scenario. 

PMID- 24726479
TI  - Comparative toxicity of silver nanoparticles on oxidative stress and DNA damage
      in the nematode, Caenorhabditis elegans.
AB  - This study examined the effects of polyvinylpyrrolidone (PVP) surface coating and
      size on the organismal and molecular toxicity of silver nanoparticles (AgNPs) on
      the nematode, Caenorhabditis elegans. The toxicity of bare AgNPs and 8 and 38 nm
      PVP-coated AgNPs (PVP8-AgNPs, PVP38-AgNPs) were compared. The toxicity of AgNO3
      was also tested because ion dissolution and particle-specific effects are often
      important characteristics determining Ag nanotoxicity. Comparative toxicity
      across AgNO3 and the three different types of AgNPs was first evaluated using a
      C. elegans mortality test by a direct comparison of the LC50 values.
      Subsequently, mutant screening followed by oxidative stress, mitochondrial
      toxicity and DNA damage assays were carried out at equitoxic (LC10 and LC50)
      concentrations to further assess the toxicity mechanism of AgNO3 and AgNPs. AgNO3
      and bare AgNPs had similar toxicities, whereas PVP coating reduced the toxicity
      of the AgNPs significantly. Of the PVP-AgNPs, the smaller NPs were more toxic.
      Different groups of mutants responded differently to AgNO3 and AgNPs, which
      indicates that their toxicity mechanism might be different. AgNO3 and bare AgNPs
      induced mitochondrial membrane damage. None of the silver materials tested caused
      detectable polymerase-inhibiting DNA lesions in either the nucleus or
      mitochondria as measured by a quantitative PCR assay, but AgNO3, bare AgNPs and
      PVP8-AgNPs induced oxidative DNA damage. These results show that coatings on the
      AgNPs surface and the particle size make a clear contribution to the toxicity of
      the AgNPs, and oxidative stress-related mitochondrial and DNA damage appear to be
      potential mechanisms of toxicity.

PMID- 24726480
TI  - Carbon and hydrogen isotope fractionation of benzene and toluene during
      hydrophobic sorption in multistep batch experiments.
AB  - The application of compound-specific stable isotope analysis (CSIA) for
      evaluating degradation of organic pollutants in the field implies that other
      processes affecting pollutant concentration are minor with respect to isotope
      fractionation. Sorption is associated with minor isotope fractionation and
      pollutants may undergo successive sorption-desorption steps during their
      migration in aquifers. However, little is known about isotope fractionation of
      BTEX compounds after consecutive sorption steps. Here, we show that partitioning
      of benzene and toluene between water and organic sorbents (i.e. 1-octanol,
      dichloromethane, cyclohexane, hexanoic acid and Amberlite XAD-2) generally
      exhibits very small carbon and hydrogen isotope effects in multistep batch
      experiments. However, carbon and hydrogen isotope fractionation was observed for
      the benzene-octanol pair after several sorption steps (Deltadelta(13)C=1.6 +/-
      0.30/00 and Deltadelta(2)H=88 +/- 30/00), yielding isotope fractionation factors
      of alphaC=1.0030 +/- 0.0005 and alphaH=1.195 +/- 0.026. Our results indicate that
      the cumulative effect of successive hydrophobic partitioning steps in an aquifer
      generally results in insignificant isotope fractionation for benzene and toluene.
      However, significant carbon and hydrogen isotope fractionation cannot be excluded
      for specific sorbate-sorbent pairs, such as sorbates with pi-electrons and
      sorbents with OH-groups. Consequently, functional groups of sedimentary organic
      matter (SOM) may specifically interact with BTEX compounds migrating in an
      aquifer, thereby resulting in potentially relevant isotope fractionation.

PMID- 24726481
TI  - N-terminal sequence tagging using reliably determined b2 ions: a useful approach
      to deconvolute tandem mass spectra of co-fragmented peptides in proteomics.
AB  - With the recent introduction of higher-energy collisional dissociation (HCD) in
      Orbitrap mass spectrometry, the popularity of that technique has grown
      tremendously in the proteomics society. HCD spectra, however, are characterized
      by a limited distribution of bn-type ions, which permit the generation of
      reliable sequence tags based on complementary b,y pairs both for de novo
      sequencing and sequence tagging strategies. Instead, most peptide HCD spectra
      (~95%) are dominated with b2 ions. In this work, we analyzed positive predictive
      values of b2 ions in HCD, and found that b2 ions can be determined with >97%
      certainty in the presence of a2 and its complementary yn-2 ions. Analytically, b2
      ions provide information on the composition of the first two N-terminal amino
      acids in peptides. Their utilization in N-terminal sequence tagging leads to a
      significant decrease in false discovery rate by filtering out false positives
      while retaining true positive identifications. As a consequence, the number of
      peptide spectrum matches (PSMs) increased by 4.8% at fixed FDR (1%). This
      approach allows for deconvolution of mixture spectra and increased the number of
      PSM to 9.2% in a complex human sample and to 24% in a complex sample of synthetic
      peptides at 1% FDR. 

PMID- 24726482
TI  - Proteomic analysis of cancer and mesothelial cells reveals an increase in Mucin
      5AC during ovarian cancer and peritoneal interaction.
AB  - Ovarian cancer is a highly metastatic disease that is often characterized by
      widespread abdominal dissemination. A hallmark of ovarian cancer progression is
      the attachment of malignant cells to the mesothelium and the formation of
      invasive peritoneal implants. Therefore, delineating factors involved in cancer
      peritoneal cell interaction is critical to improving patient survival, as it may
      lead to the discovery of novel therapeutic targets. As such, we aimed to identify
      proteins that participate in this interaction by comparing the secreted proteome
      of a co-culture model containing ovarian cancer (OVCAR-5) and mesothelial cells
      (LP-9), to their respective monoculture secretomes. In total, 49 proteins were
      differentially secreted during cancer and mesothelial cell contact. Relative mRNA
      expression of candidates was performed, which revealed a significant increase in
      MUC5AC gene expression in cancer cells cultured in three different co-culture
      models (OVCAR-5 and LP-9; BG-1 and LP-9; OV-90 and LP-9). An increased expression
      was also observed in LP-9 cells that were co-cultured with OVCAR-5 and OV-90
      cancer cells. Further immunocytochemistry analysis also confirmed increased
      expression of MUC5AC in ovarian cancer and peritoneal co-cultures. Overall, our
      analysis uncovers novel molecular markers of peritoneal metastasis, which may
      have potential roles in regulating the progression of the disease. BIOLOGICAL
      SIGNIFICANCE: In this study, our objective was to focus on identifying novel
      mediators of ovarian cancer and peritoneal interaction using a mass spectrometry
      based approach. Our analysis resulted in the discovery of both previously known
      and novel factors involved this interaction, and as such, these newly discovered
      proteins might have potential roles in cancer progression, such as invasion and
      adhesion. We believe that these findings add to our current knowledge and
      understanding of ovarian cancer progression, and will aid researchers in their
      future attempts in finding new targets of the disease.

PMID- 24726483
TI  - Beta cell imaging - a key tool in optimized diabetes prevention and treatment.
AB  - The prevalence of diabetes is 382 million worldwide, and is expected to rise to
      592 million in 2035 (http://www.idf.org/diabetesatlas); 2.5-15% of national
      annual healthcare budgets are related to diabetes care, potentially increasing to
      40% in high-prevalence countries. Beta cell dysfunction and death are central
      events in diabetes pathogenesis, but the natural history of beta cell loss
      remains unknown. Clinical imaging of beta cells will play a pivotal role in
      developing strategies for optimized diabetes prevention and treatment. 

PMID- 24726484
TI  - Measuring shoulder external and internal rotation strength and range of motion:
      comprehensive intra-rater and inter-rater reliability study of several testing
      protocols.
AB  - BACKGROUND: Shoulder range of motion (ROM) and strength measurements are
      imperative in the clinical assessment of the patient's status and progression
      over time. The method and type of assessment varies among clinicians and
      institutions. No comprehensive study to date has examined the reliability of a
      variety of procedures based on different testing equipment and specific patient
      or shoulder position. The purpose of this study was to establish absolute and
      relative reliability for several procedures measuring the rotational shoulder ROM
      and strength into internal (IR) and external (ER) rotation strength. METHODS:
      Thirty healthy individuals (15 male, 15 female), with a mean age of 22.1 +/- 1.4
      years, were examined by 2 examiners who measured ROM with a goniometer and
      inclinometer and isometric strength with a hand-held dynamometer (HHD) in
      different patient and shoulder positions. Relative reliability was determined by
      intraclass correlation coefficients (ICC). Absolute reliability was quantified by
      standard error of measurement (SEM) and minimal detectable change (MDC).
      Systematic differences across trials or between testers, as well as differences
      among similar measurements under different testing circumstances, were analyzed
      with dependent t tests or repeated-measures analysis of variance in case of 2 or
      more than 2 conditions, respectively. RESULTS: Reliability was good to excellent
      for IR and ER ROM and isometric strength measurements, regardless of patient or
      shoulder position or equipment used (ICC, 0.85-0.99). For some of the
      measurements, systematic differences were found across trials or between testers.
      The patient's position and the equipment used resulted in different outcome
      measures. CONCLUSIONS: All procedures examined showed acceptable reliability for
      clinical use. However, patient position and equipment might influence the
      results.

PMID- 24726485
TI  - Arthroscopic debridement for primary osteoarthritis of the elbow: analysis of
      preoperative factors affecting outcome.
AB  - BACKGROUND: The purposes of this study were to evaluate the clinical results of
      arthroscopic debridement and to identify preoperative factors that influence the
      outcome. METHODS: Forty-three elbows with primary osteoarthritis in 43 patients
      treated with arthroscopic debridement were retrospectively evaluated. At a mean
      follow-up of 38 months (range, 18-77 months), the visual analog scale (VAS) score
      for pain, the arc of elbow motion, and the Mayo Elbow Performance Index (MEPI)
      score were assessed. The relationships between postoperative MEPI score and
      postoperative motion arc and preoperative factors including age, sex, involvement
      of the dominant arm, duration of symptoms, demand of elbow activity, VAS score,
      previous history of failed surgery, and arc of elbow motion were statistically
      evaluated. RESULTS: The mean VAS score for pain, the mean arc of flexion
      extension, and the mean MEPI score significantly improved after the operation
      (all P values < .001). Multivariate regression analysis revealed that among
      preoperative variables, arc of motion was found to be the only independent
      prognostic factor that affected both postoperative elbow function (P = .024) and
      final arc of motion (P < .001). The cutoff value of preoperative arc of motion
      for the final arc of motion was determined to be 80 degrees  (P < .001).
      Involvement of the dominant arm was found to be another independent factor that
      affected postoperative MEPI scores (P = .016). CONCLUSIONS: Arthroscopic
      debridement for elbow osteoarthritis provides satisfactory pain relief,
      improvement of elbow motion, and good functional outcome. Based on the fact that
      preoperative motion arc is the independent factor that can predict clinical
      outcome, arthroscopic treatment is highly recommended for patients who have a
      motion arc of 80 degrees  or more as it yields reliable results.

PMID- 24726486
TI  - Minimal important changes in the Constant-Murley score in patients with
      subacromial pain.
AB  - OBJECTIVE: The purpose of this study was to determine the minimal important
      change (MIC) of improvement in the Constant-Murley score in patients with long
      standing subacromial pain and in subgroups of patients with subacromial pain with
      and without rotator cuff ruptures. METHOD: The MIC was estimated by the anchor
      based MIC distribution method, which integrates an anchor- and distribution-based
      approach: the optimal cutoff point of the receiver operating characteristic curve
      (MICROC) and the 95% limit cutoff point (MIC95% limit). The study population
      consisted of 93 patients included in a randomized clinical trial evaluating the
      effect of a specific exercise strategy. RESULTS: The MICROC was found at a mean
      change of 17 points in the Constant-Murley score, which corresponds to a
      sensitivity of 91% and a specificity of 79%. The MIC95% limit was found at a mean
      change of 24 points. In the subgroup analysis, the MICROC was found at a mean
      change of 19 points and the MIC95% limit at 18 points in patients with an intact
      rotator cuff. In patients with rotator cuff ruptures, the MICROC was found at a
      mean change of 15 points and the MIC95% limit at 30 points. CONCLUSION: The
      Constant-Murley score is able to detect the MIC in individual patients with long
      standing subacromial pain when the rotator cuff is intact. The estimated MIC
      values could be used as an indication for relevant changes in the Constant-Murley
      score in clinical practice and guide the clinician in how to interpret the
      results of specific treatments.

PMID- 24726487
TI  - The difference in spatiotemporal dynamics between modus ponens and modus tollens
      in the Wason selection task: an event-related potential study.
AB  - High-density, event-related brain potentials (ERPs) were recorded to explore
      differences in spatiotemporal dynamics between modus ponens (MP) and modus
      tollens (MT) in the Wason selection task. Results showed that MP elicits a more
      positive P3b-like component than MT from 400 to 800 ms. MP appeared to occur
      earlier than MT in various stages of proposition testing, such as stimulus
      processing and response selection. ERP results showed that MT has a longer
      duration and more negative later negative component (LNC) than MP at 2,000 ms.
      This result suggests that MT occupies more cognitive resources than MP in the
      final stages of proposition testing. The short and small left frontal LNC
      obtained by MP implies examination of the expectable conclusion, whereas the long
      and large left frontal LNC elicited by MT may be involved in the retention
      operation of the card in working memory from the monitoring and inspecting
      putative conclusion in the later stages of proposition testing.

PMID- 24726488
TI  - GDNF is important for striatal organization and maintenance of dopamine neurons
      grown in the presence of the striatum.
AB  - Glial cell line-derived neurotrophic factor (GDNF) exerts neuroprotective and
      neurorestorative effects on neurons and GDNF plays a significant role in
      maintenance of the dopamine neurons utilizing grafting to create a nigrostriatal
      microcircuit of Gdnf knockout (Gdnf(-/-)) tissue. To further evaluate the role of
      GDNF on organization of the nigrostriatal system, single or double grafts of
      ventral mesencephalon (VM) and lateral ganglionic eminence (LGE) with mismatches
      in Gdnf genotypes were performed. The survival of single grafts was monitored
      utilizing magnetic resonance imaging (MRI) and cell survival and graft
      organization were evaluated with immunohistochemistry. The results revealed that
      the size of VM single grafts did not change over time independent of genotype,
      while the size of the LGE transplants was significantly reduced already at 2
      weeks postgrafting when lacking GDNF. Lack of GDNF did not significantly affect
      the survival of tyrosine hydroxylase (TH)-positive neurons in single VM grafts.
      However, the survival of TH-positive neurons was significantly reduced in VM
      derived from Gdnf(+/+) when co-grafted with LGE from the Gdnf(-/-) tissue. In
      contrast, lack of GDNF in the VM portion of co-grafts had no effect on the
      survival of TH-positive neurons when co-grafted with LGE from Gdnf(+/+) mice. The
      TH-positive innervation of co-grafts was sparse when the striatal co-grafts were
      derived from the Gdnf(-/-) tissue while dense and patchy when innervating LGE
      producing GDNF. The TH-positive innervation overlapped with the organization of
      dopamine and cyclic AMP-regulated phosphoprotein-relative molecular mass 32,000
      (DARPP-32)-positive neurons, that was disorganized in LGE lacking GDNF
      production. In conclusion, GDNF is important for a proper striatal organization
      and for survival of TH-positive neurons in the presence of the striatal tissue.

PMID- 24726490
TI  - Open, sesame! The gateway to mitigate hepatic injury using sesamin.

PMID- 24726489
TI  - A two-locus model of spatially varying stabilizing or directional selection on a
      quantitative trait.
AB  - The consequences of spatially varying, stabilizing or directional selection on a
      quantitative trait in a subdivided population are studied. A deterministic two
      locus two-deme model is employed to explore the effects of migration, the degree
      of divergent selection, and the genetic architecture, i.e., the recombination
      rate and ratio of locus effects, on the maintenance of genetic variation. The
      possible equilibrium configurations are determined as functions of the migration
      rate. They depend crucially on the strength of divergent selection and the
      genetic architecture. The maximum migration rates are investigated below which a
      stable fully polymorphic equilibrium or a stable single-locus polymorphism can
      exist. Under stabilizing selection, but with different optima in the demes,
      strong recombination may facilitate the maintenance of polymorphism. However
      usually, and in particular with directional selection in opposite direction, the
      critical migration rates are maximized by a concentrated genetic architecture,
      i.e., by a major locus and a tightly linked minor one. Thus, complementing
      previous work on the evolution of genetic architectures in subdivided populations
      subject to diversifying selection, it is shown that concentrated architectures
      may aid the maintenance of polymorphism. Conditions are obtained when this is the
      case. Finally, the dependence of the phenotypic variance, linkage disequilibrium,
      and various measures of local adaptation and differentiation on the parameters is
      elaborated. 

PMID- 24726491
TI  - Assessing the necessity of including a crossover period with dual reporting when
      changing total prostate-specific antigen methods.
AB  - OBJECTIVES: Options are limited for the laboratory when changing analytical
      methods for tumor markers. Standardization between methods should alleviate this
      burden. Our objective was to assess the necessity of dual reporting for total
      prostate-specific antigen (tPSA) when changing methods that have been calibrated
      against the World Health Organization PSA reference material. DESIGN AND METHODS:
      Following an initial validation where 40 patient samples were divided and
      analyzed on the Roche E-modular (current method) and Abbott ARCHITECT (new
      method) for tPSA, a crossover period ensued with dual reporting of tPSA over
      54days (n=1110 samples with both tPSA results reported). Passing & Bablok
      regression was performed, with agreement during the crossover period also
      determined by two methods. Method#1: if the percent difference between the result
      pair was <=0.33*the intraindividual biological variation (0.33*CVi=6.0%) for
      tPSA; and Method#2: if the Roche tPSA result was within an acceptable analytical
      range based on Abbott's maximum allowable imprecision for the tPSA assay (CV<=8%)
      to determine if there was a range of optimal agreement that might not require
      dual reporting. RESULTS: During the crossover period, Passing & Bablok regression
      yielded the following relationship: Abbott tPSA=1.04(95% CI: 1.03 to 1.04)*(Roche
      tPSA)-0.02(95% CI: -0.03 to -0.02). Only 52% (95%CI: 49 to55) of the results were
      in agreement by Method#1 whereas 95% (95% CI: 92 to 97) of the results between
      3.3 and 19MUg/L were found to have acceptable agreement based on Method#2.
      CONCLUSIONS: These findings suggest that dual reporting of tPSA is required when
      changing methods. However, the extent of dual reporting may be limited to
      specific concentration ranges with future studies required to validate selective
      dual reporting when changing tPSA assays.

PMID- 24726492
TI  - Multiplex detection of KRAS mutations by a matrix-assisted laser
      desorption/ionization-time of flight mass spectrometry assay.
AB  - OBJECTIVES: Mutations of the Kirsten rat sarcoma viral oncogene (KRAS) gene are
      known to be important in the pathogenesis of a variety of cancers. Patients with
      mutant KRAS tumors do not respond to epidermal growth factor receptor (EGFR)
      inhibitors and fail to benefit from adjuvant chemotherapy. Testing for KRAS
      mutations is now being recommended as a tailored therapeutic strategy prior to
      anti-EGFR treatment; however, the low sensitivity of direct sequencing frequently
      leads to failure of detection of KRAS mutations in clinical samples. DESIGN AND
      METHODS: We developed restriction fragment mass polymorphism (RFMP) assays, to
      detect KRAS mutations in codons 12, 13, and 61. We performed RFMP analysis for
      KRAS on DNA isolated from eight different KRAS mutant cell lines and 34 formalin
      fixed paraffin-embedded (FFPE) lung cancer tissues. RESULTS: Overall, the RFMP
      assay was in good concordance with direct sequencing analysis in the detection of
      KRAS mutations. By using dilutions of KRAS mutant DNA in wild type DNA from
      mutation cell lines with a known KRAS status, we confirmed that the RFMP assay
      has a higher analytical sensitivity, requiring only 3% of cells in a sample to
      have mutant alleles, compared to direct sequencing, which had a detection
      threshold of ~25%. In the FFPE samples, RFMP successfully detected KRAS genotypes
      in codons 12, 13, and 61. CONCLUSION: The RFMP might be efficiently applicable
      for the detection of KRAS mutations in a clinical setting, particularly for tumor
      samples containing abundant non-neoplastic cells.

PMID- 24726493
TI  - Pediatric reference value distributions for vitamins A and E in the CALIPER
      cohort and establishment of age-stratified reference intervals.
AB  - OBJECTIVES: Vitamin A (retinol) and vitamin E (alpha-tocopherol) are fat soluble
      micronutrients most commonly measured in the pediatric population to monitor
      deficiencies due to malabsorption secondary to gastrointestinal (GI) disorders.
      One of the major challenges of vitamin A and E testing is the lack of reliable
      pediatric reference intervals which limits accurate interpretation of results.
      Here we report new pediatric reference intervals (RI) for both vitamins as part
      of the Canadian Laboratory Initiative for Pediatric Reference Intervals
      (CALIPER). DESIGN AND METHODS: A total of 342 blood samples were collected from
      healthy children 1 day to 19 years of age recruited from the community. Retinol
      and alpha-tocopherol were extracted from serum using hexane before concentrations
      were measured with high-performance liquid chromatography (HPLC). Age and sex
      specific RI were calculated with guidance from CLSI C28-A2. Non-parametric and
      robust methods were used to calculate the 95th percentile ranges of the reference
      intervals along with the 90% confidence intervals. RESULTS: Vitamin A
      demonstrated increasing levels with age necessitating four distinct age
      stratifications. Vitamin E levels peaked within the first year of life requiring
      only 2 age partitions. Ratios of vitamin E to cholesterol and triglyceride were
      also calculated, and correlated well to vitamin E levels. Sex-specific
      differences were not observed. CONCLUSIONS: This study establishes pediatric RI
      for vitamins A and E in a healthy population of children from neonates to early
      adulthood. These values will be beneficial in assessing accurate vitamin status
      when monitoring children with GI disorders or malnutrition.

PMID- 24726494
TI  - Osteoporosis in men.
AB  - Osteoporosis in men causes significant morbidity and mortality. Bone health
      declines gradually, often insidiously; and in light of the advancing aging
      population poses a serious public health issue that is not well recognized.
      Studies of the past decade have expanded our understanding of the events within,
      as well as the regulation of, bone remodeling and provided better insight into
      the physiology and pathophysiology specific to the adult male skeleton. The
      clinical measurement of bone mineral density using dual-energy X-ray
      absorptiometry remains the gold standard for diagnosis of osteoporosis in males;
      and fracture risk assessment is now recognized as a preferred approach to guide
      treatment decisions. Utilizing surrogate end-points such as increasing bone
      mineral density and decreasing concentrations of bone resorption markers,
      clinical trials have demonstrated efficacy in pharmacological treatment of
      osteoporosis in the adult male. Unfortunately, few studies have evaluated the
      anti-fracture benefits in this population. Measurement of bone turnover markers
      may be an additional tool to monitor therapeutic responsiveness in addition to
      the measurement of bone mineral density. 

PMID- 24726495
TI  - A novel therapeutic approach for the treatment of central sleep apnea: The
      remede(r) system.
AB  - Central sleep apnea (CSA) occurs primarily in cardiovascular patients and is
      associated with high morbidity and mortality. The disorder often is unrecognized
      due to the overlap of symptoms with those of the underlying cardiac disease. CSA
      can be easily diagnosed with a sleep study. Following optimization of all co
      morbidities, the therapeutic approach available currently focuses on mask-based
      therapies which suffer from poor patient adherence. A new therapy, the remede(r)
      System, has been developed; it utilizes a transvenous, fully implantable system
      providing phrenic nerve stimulation intended to restore a more normal breathing
      pattern. The therapy demonstrated promising results based on an initial chronic
      study and a randomized trial is underway to further evaluate safety and efficacy
      of this novel system in patients with CSA.

PMID- 24726496
TI  - Ezrin is down-regulated in diabetic kidney glomeruli and regulates actin
      reorganization and glucose uptake via GLUT1 in cultured podocytes.
AB  - Diabetic nephropathy is a complication of diabetes and a major cause of end-stage
      renal disease. To characterize the early pathophysiological mechanisms leading to
      glomerular podocyte injury in diabetic nephropathy, we performed quantitative
      proteomic profiling of glomeruli isolated from rats with streptozotocin-induced
      diabetes and controls. Fluorescence-based two-dimensional difference gel
      electrophoresis, coupled with mass spectrometry, identified 29 differentially
      expressed spots, including actin-binding protein ezrin and its interaction
      partner, NHERF2, which were down-regulated in the streptozotocin group. Knockdown
      of ezrin by siRNA in cultured podocytes increased glucose uptake compared with
      control siRNA-transfected cells, apparently by increasing translocation of
      glucose transporter GLUT1 to the plasma membrane. Knockdown of ezrin also induced
      actin remodeling under basal conditions, but reduced insulin-stimulated actin
      reorganization. Ezrin-dependent actin remodeling involved cofilin-1 that is
      essential for the turnover and reorganization of actin filaments. Phosphorylated,
      inactive cofilin-1 was up-regulated in diabetic glomeruli, suggesting altered
      actin dynamics. Furthermore, IHC analysis revealed reduced expression of ezrin in
      the podocytes of patients with diabetes. Our findings suggest that ezrin may play
      a role in the development of the renal complication in diabetes by regulating
      transport of glucose and organization of the actin cytoskeleton in podocytes. 

PMID- 24726497
TI  - Conditional knockout of pik3c3 causes a murine muscular dystrophy.
AB  - Abnormalities in phosphoinositide metabolism are an emerging theme in human
      neurodegenerative disease. Myotubular myopathy is a prototypical disorder of
      phosphoinositide dysregulation that is characterized by profound muscle pathology
      and weakness and that is caused by mutations in MTM1, which encodes a phosphatase
      that targets 3-position phosphoinositides, including phosphatidylinositol 3
      phosphate. Although the association between MTM1 and muscle disease has become
      increasingly clarified, the normal role(s) of phosphatidylinositol 3-phosphate
      metabolism in muscle development and homeostasis remain poorly understood. To
      begin to address the function of phosphatidylinositol 3-phosphate in skeletal
      muscle, we focused on the primary kinase responsible for its production, and
      created a muscle-specific conditional knockout of the class III
      phosphatidylinositol 3-kinase, Pik3c3. Muscle-specific deletion of Pik3c3 did not
      disturb embryogenesis or early postnatal development, but resulted in progressive
      disease characterized by reduced activity and death by 2 months of age.
      Histopathological analysis demonstrated changes consistent with a murine muscular
      dystrophy. Examination for cellular mechanism(s) responsible for the dystrophic
      phenotype revealed significant alterations in the autophagolysosomal pathway with
      mislocation of known dystrophy proteins to the lysosomal compartment. In all, we
      present the first analysis of Pik3c3 in skeletal muscle, and report a novel
      association between deletion of Pik3c3 and muscular dystrophy. 

PMID- 24726498
TI  - IL-27R-mediated regulation of IL-17 controls the development of respiratory
      syncytial virus-associated pathogenesis.
AB  - IL-27 is a heterodimeric cytokine composed of the subunits p28 and Epstein-Barr
      virus induced gene (EBI)-3 and is known for its effects on T-cell function and
      differentiation. IL-27 signals through the widely expressed IL-27 receptor (IL
      27R), composed of the ligand-specific IL-27Ralpha chain and gp130. Engagement of
      the IL-27R activates STAT1 signaling, induces the expression of the type 1 helper
      T-cell (Th1) cytokine, interferon gamma, and suppresses the differentiation of
      Th2 and Th17 cells. This study investigates the role of IL-27 signaling in
      respiratory syncytial virus (RSV) infection using IL-27Ralpha-deficient mice (IL
      27rKO). Analysis of lungs from RSV-infected IL-27rKO mice showed exacerbation of
      mucus secretion compared with wild type, as well as enhanced expression of Muc5ac
      and Gob5 mRNA, markers of goblet cell metaplasia/hyperplasia. When compared with
      wild-type mice, RSV-challenged IL-27rKO mice had enhanced expression of Th17
      associated cytokine IL-17a and an imbalance between Th1 and Th2 cytokine levels.
      Neutralization of IL-17 in RSV-infected IL-27rKO mice resulted in a significant
      decrease in the pulmonary mucus response and inhibition of the Th2-associated
      cytokines. Interestingly, IL-17 blockage led to an increase in the expression of
      IL-27 subunits p28 and EBI-3 in the lungs and lymph nodes of RSV-infected mice.
      Thus, IL-27 functions as a regulatory cytokine during RSV pathogenesis by
      suppressing the development of Th17 cells, but it also appears to be regulated by
      IL-17 induced by the virus. 

PMID- 24726500
TI  - Resveratrol inhibition of human keratinocyte proliferation via SIRT1/ARNT/ERK
      dependent downregulation of aquaporin 3.
AB  - BACKGROUND: Aquaporin 3 (AQP3) is the predominant aquaporin in the skin and is
      overexpressed in hyperplastic epidermal disorders. Upregulation of AQP3
      contributes to keratinocyte proliferation and epidermal hyperplasia. Resveratrol,
      a natural polyphenol, has an anti-proliferative effect on normal human epidermal
      keratinocytes (NHEKs), but its exact mechanism remains largely unknown.
      OBJECTIVE: To investigate the ability and mechanism of resveratrol to affect the
      proliferation and the AQP3 expression in NHEKs. METHODS: NHEKs treated with
      resveratrol were analyzed. BrdU incorporation assay, real-time PCR, Western
      blotting and RNA interference using small interfering RNA were employed. RESULTS:
      At non-toxic concentrations (less than 40MUM), resveratrol inhibited the
      proliferation of NHEKs. Resveratrol inhibited the ERK phosphorylation and the
      AQP3 expression with reciprocal upregulation of ARNT expression in a
      concentration-dependent manner. The inhibitory effects of resveratrol on the ERK
      phosphorylation and the AQP3 expression were canceled by transfection of siRNA
      for ARNT, but not by that for AhR. Furthermore, the induction effect of
      resveratrol on ARNT expression was canceled after SIRT1 was knocked down in
      NHEKs. CONCLUSION: Resveratrol inhibited NHEK proliferation by downregulating the
      expression of AQP3 in an SIRT1/ARNT/ERK dependent fashion. This novel mechanism
      may facilitate drug innovation for hyperplastic skin disorders.

PMID- 24726499
TI  - Matrix biology of idiopathic pulmonary fibrosis: a workshop report of the
      national heart, lung, and blood institute.
AB  - A hallmark of idiopathic pulmonary fibrosis (IPF) is excessive and disordered
      deposition of extracellular matrix. Although the lung extracellular matrix
      normally plays an essential role in development and maintenance of lung tissue
      through reciprocal interactions with resident cells, the disordered matrix in the
      diseased lung is increasingly recognized as an active and important contributor
      to IPF pathogenesis. This working group summary from a recently conducted
      National Heart, Lung, and Blood Institute strategic planning workshop for IPF
      research highlights recent advances, challenges, and opportunities in the study
      of matrix biology in IPF. Particular attention is given to the composition and
      mechanical properties of the matrix in normal and diseased lungs, and the
      biochemical and biomechanical influences exerted by pathological matrix. Recently
      developed model systems are also summarized as key tools for advancing our
      understanding of matrix biology in IPF. Emerging approaches to therapeutically
      target the matrix in preclinical and clinical settings are discussed, as are
      important concepts, such as alterations of the matrix with aging and the
      potential for the resolution of fibrosis. Specific recommendations for future
      studies in matrix biology of IPF are also proposed. 

PMID- 24726501
TI  - A nucleic acid-based medication for allergic skin diseases.
AB  - Among allergic skin diseases, atopic dermatitis is the most difficult to cure. In
      the majority of patients, atopic dermatitis can be easily controlled by treatment
      based on three therapeutic approaches: avoidance of precipitating factors, skin
      care, and medication. In some adult patients, however, severe atopic dermatitis
      is refractory to treatment, and no fundamental effective treatment modality has
      yet been established for such cases. Chronic contact dermatitis without an
      identified causative hapten is also considered an allergic skin disease that is
      difficult to cure. Topical nucleic acid-based medications are currently being
      applied clinically, and an ointment containing nuclear factor-kappaB decoy
      oligodeoxynucleotides (hereafter referred to as Decoy) has reached clinical
      trials. In addition, synthetic double-stranded DNA with high affinity for signal
      transducers and activators of transcription 6 (STAT6) introduced in vivo as a
      decoy cis element to bind the transcriptional factor and block the activated gene
      that contributes to the onset and progression of atopic dermatitis functions as
      an effective therapeutic agent. We also introduce another STAT1 decoy treatment,
      cytosine-phosphate-guanine-ODN or STAT6 small interfering RNA therapy, for
      allergic skin diseases. 

PMID- 24726502
TI  - Telehealth interventions for primary prevention of cardiovascular disease: a
      systematic review and meta-analysis.
AB  - OBJECTIVE: To assess the effectiveness of telehealth interventions in the primary
      prevention of cardiovascular disease in adult patients in community settings.
      METHODS: Systematic literature review of randomised controlled trials comparing
      the effectiveness of telehealth interventions to reduce overall cardiovascular
      disease (CVD) risk and/or to reduce multiple CVD risk factors compared with a non
      telehealth control group was conducted in June 2013. Study quality was assessed
      using the Cochrane Risk of Bias tool. Fixed and random effects models were
      combined with a narrative synthesis for meta-analysis of included studies.
      RESULTS: Three of 13 included studies measured Framingham 10-year CVD risk
      scores, and meta-analysis showed no clear evidence of reduction in overall risk
      (SMD -0.37%, 95% CI -2.08, 1.33). There was weak evidence for a reduction in
      systolic blood pressure (SMD -1.22 mmHg 95% CI -2.80, 0.35) and total cholesterol
      (SMD -0.07 mmol/L 95% CI -0.19, 0.06). There was no change in High-Density
      Lipoprotein cholesterol or smoking rates. CONCLUSION: There is insufficient
      evidence to determine the effectiveness of telehealth interventions in reducing
      overall CVD risk. More studies are needed that consistently measure overall CVD
      risk, directly compare different telehealth interventions, and determine cost
      effectiveness of telehealth interventions for prevention of CVD.

PMID- 24726503
TI  - X marks the spot: Duchenne's cardiomyopathy.

PMID- 24726504
TI  - A novel vaccine against Porcine circovirus type 2 (PCV2) and Streptococcus equi
      ssp. zooepidemicus (SEZ) co-infection.
AB  - To develop a vaccine against Porcine circovirus type 2 (PCV2) and Streptococcus
      equi ssp. zooepidemicus (SEZ) co-infection, the genes of porcine IL-18, capsid
      protein (Cap) of PCV2 and M-like protein (SzP) of SEZ were inserted into the
      swinepox virus (SPV) genome by homologous recombination. The recombinant swinepox
      virus rSPV-ICS was verified by PCR and indirect immunofluorescence assays. To
      evaluate the immunogenicity of rSPV-ICS, 28 PCV2 and SEZ seronegative Bama
      minipigs were immunized with rSPV-ICS (n=8), commercial PCV2 vaccine and SEZ
      vaccine (n=8) or wild type SPV (n=8). The results showed that SzP-specific
      antibody and PCV2 neutralizing antibody of the rSPV-ICS immunized group increased
      significantly compared to the wild type SPV treated group after vaccination and
      increased continuously over time. The levels of IL-4 and IFN-gamma in the rSPV
      ICS immunized group were significantly higher than the other three groups,
      respectively. After been co-challenged with PCV2 and SEZ, 87.5% piglets in rSPV
      ICS immunized group were survived. Significant reductions in gross lung lesion
      score, histopathological lung lesion score, and lymph node lesion score were
      noticed in the rSPV-ICS immunized group compared with the wtSPV treated group.
      The results suggested that the recombinant rSPV-ICS provided piglets with
      significant protection against PCV2-SEZ co-infection; thus, it offers proof-of
      principle for the development of a vaccine for the prevention of these swine
      diseases. 

PMID- 24726505
TI  - Antimicrobial resistance in bacteria associated with porcine respiratory disease
      in Australia.
AB  - The porcine respiratory disease complex greatly affects the health and production
      of pigs. While antimicrobial agents are used to treat the respiratory infections
      caused by bacterial pathogens, there is no current information on antimicrobial
      resistance in Australian pig respiratory bacterial isolates. The aim of this
      study was to determine the antimicrobial resistance profiles, by determining the
      minimum inhibitory concentration of nine antimicrobial agents for 71
      Actinobacillus pleuropneumoniae, 51 Pasteurella multocida and 18 Bordetella
      bronchiseptica cultured from Australian pigs. The majority of A. pleuropneumoniae
      isolates were resistant to erythromycin (89%) and tetracycline (75%). Resistance
      to ampicillin (8.5%), penicillin (8.5%) and tilmicosin (25%) was also identified.
      The P. multocida isolates exhibited resistance to co-trimoxazole (2%),
      florfenicol (2%), ampicillin (4%), penicillin (4%), erythromycin (14%) and
      tetracycline (28%). While all the B. bronchiseptica isolates showed resistance to
      beta-lactams (ampicillin, ceftiofur and penicillin), some were resistant to
      erythromycin (94%), florfenicol (6%), tilmicosin (22%) and tetracycline (39%).
      The incidence of multiple drug resistance (MDR) varied across the species - in B.
      bronchiseptica, 27.8% of resistant isolates showed MDR, while 9.1% of the
      resistant isolates in A. pleuropneumoniae, and 4.8% in P. multocida showed MDR.
      This study illustrated that Australian pig strains of bacterial respiratory
      pathogens exhibited low levels of resistance to antimicrobial agents commonly
      used in the pig industry. 

PMID- 24726506
TI  - Neonatal eating epilepsy: 50-year follow-up.
AB  - PURPOSE: We present a case of neonatal eating epilepsy. METHOD: Case report.
      RESULTS: An otherwise healthy female newborn started having epileptic seizures
      lasting up to 5 minutes induced by breastfeeding at age of 2 weeks. The
      convulsive seizure started with crying and coughing followed by opisthotonus,
      flexion of upper extremities, extension of lower extremities, and generalized
      jerks in extremities. The patient had fairly often postictal vomitings which
      could not be relieved by upright positioning. At baseline clinical examination,
      no abnormal symptoms or signs were found except for a postictal hoarseness. On
      the day of admission to the tertiary care hospital, during 1.5 hours, she had 10
      attacks. Though some attacks were spontaneous and during sleep, most were induced
      by feeding or--less often and inconsistently--by manipulating the pharynx.
      Phenobarbital 15 mg four times a day stopped the attacks. The last seizure was
      documented 14 days after admission and phenobarbital was eventually withdrawn.
      The patient remained seizure free off AEDs during a prospective follow-up for
      over 50 years until 2013. CONCLUSIONS: Neonatal eating epilepsy may be a suitable
      diagnosis if convulsive seizures are precipitated by feeding or eating.
      Polygraphic recording will help ascertain the diagnosis. Antiepileptic therapy is
      likely to abolish seizures.

PMID- 24726507
TI  - Removal versus retention of cerclage in preterm premature rupture of membranes: a
      randomized controlled trial.
AB  - OBJECTIVE: The decision of whether to retain or remove a previously placed
      cervical cerclage in women who subsequently rupture fetal membranes in a
      premature gestation is controversial and all studies to date are retrospective.
      We performed a multicenter randomized controlled trial of removal vs retention of
      cerclage in these patients to determine whether leaving the cerclage in place
      prolonged gestation and/or increased the risk of maternal or fetal infection.
      STUDY DESIGN: A prospective randomized multicenter trial of 27 hospitals was
      performed. Patients included were those with cerclage placement at <=23 weeks 6
      days in singleton or twin pregnancies, with subsequent spontaneous rupture of
      membranes between 22 weeks 0 days and 32 weeks 6 days. Patients were randomized
      to retention or removal of cerclage. Patients were then expectantly managed and
      delivered only for evidence of labor, chorioamnionitis, fetal distress, or other
      medical or obstetrical indications. Management after 34 weeks was at the
      clinician's discretion. RESULTS: The initial sample size calculation determined
      that a total of 142 patients should be included but after a second interim
      analysis, futility calculations determined that the conditional power for showing
      statistical significance after randomizing 142 patients for the primary outcome
      of prolonging pregnancy was 22.8%. Thus the study was terminated after a total of
      56 subjects were randomized with complete data available for analysis, 32 to
      removal and 24 to retention of cerclage. There was no statistical significance in
      primary outcome of prolonging pregnancy by 1 week comparing the 2 groups (removal
      18/32, 56.3%; retention 11/24, 45.8%) P = .59; or chorioamnionitis (removal 8/32,
      25.0%; retention 10/24, 41.7%) P = .25, respectively. There was no statistical
      difference in composite neonatal outcomes (removal 16/33, 50%; retention 17/30,
      56%), fetal/neonatal death (removal 4/33, 12%; retention 5/30, 16%); or
      gestational age at delivery (removal mean 200 days; retention mean 198 days).
      CONCLUSION: Statistically significant differences were not seen in prolongation
      of latency, infection, or composite neonatal outcomes. However, there was a
      numerical trend in the direction of less infectious morbidity, with immediate
      removal of cerclage. These findings may not have met statistical significance if
      the original sample size of 142 was obtained, however they provide valuable data
      suggesting that there may be no advantage to retaining a cerclage after preterm
      premature rupture of membranes and a possibility of increased infection with
      cerclage retention.

PMID- 24726508
TI  - Traveling for care: inter-regional mobility for aortic valve substitution in
      Italy.
AB  - Patient flows across the regions of the Italian National Health Service can shed
      light on patient mobility, including cross-border flows within the European
      Union. We used 2009 data on 11,531 NHS admissions for aortic valve replacement
      operations to measure the extent of inter-regional patient mobility and to
      determine whether resident and non-resident patients differ. We also investigated
      whether public and private hospitals behave differently in terms of attracting
      patients. For this major cardio-surgical intervention, patient mobility in Italy
      is substantial (13.6% of total admissions). Such mobility mainly involves
      patients moving from southern to northern regions, which often requires several
      hundred kilometers of travel and a transfer of financial resources from poorer to
      richer regions. Patients admitted in the regions where they reside are older than
      those admitted outside their regions (69.2 versus 65.6, p<0.0001), and stay in
      hospital approximately 0.7 days longer (14.7 versus 14.0, p=0.017). Compared to
      public hospitals, private hospitals are more likely to admit non-resident
      patients (OR between 2.1 and 4.4). The extent and direction of patients' mobility
      raise equity concerns, as receiving care in locations that are distant from home
      requires substantial financial and relational resources. 

PMID- 24726509
TI  - Systematic review of factors affecting pharmaceutical expenditures.
AB  - OBJECTIVE: To systematically identify the main factors contributing to the
      increase in pharmaceutical expenditures. METHODS: A systematic search of
      published studies was conducted utilising major widely used electronic databases
      using the search terms 'factors,' 'financing,' 'pharmaceutical,' and
      'expenditures.' To be included, the studies needed to: (1) measure at least one
      of the following outcomes: total growth in pharmaceutical expenditures, price
      growth or quantity growth; (2) mention a clear method for analysing the impact of
      factors affecting the increases in drug expenditures; (3) be written in English.
      Nonprimary articles that were published only as an abstract, a review, a
      commentary or a letter were excluded. MAIN RESULTS: From a total of 2039 studies,
      only 25 were included in the full review. The main determinant categories that
      were identified in the review were factors related to price, utilisation,
      therapeutic choice, demand and health care system. CONCLUSIONS: The major cost
      drivers were found to be changes in drug quantities and therapies as well as new
      drugs. It is important for policymakers to understand pharmaceutical spending
      trends and the factors that influence them in order to formulate effective cost
      containment strategies and design optimum drug policy.

PMID- 24726510
TI  - Assessment of the levels of polycyclic aromatic hydrocarbons and organochlorine
      contaminants in bottlenose dolphins (Tursiops truncatus) from the Eastern
      Atlantic Ocean.
AB  - The concentrations of 18 polychlorinated biphenyls (PCBs), 23 organochlorine
      pesticides (OCPs), and 16 polycyclic aromatic hydrocarbons (PAHs) were determined
      in the blubber and liver of 27 bottlenose dolphins (Tursiops truncatus) stranded
      along the Canary Islands coasts from 1997 to 2011. DDTs (mean of 60,960 and 445
      ng/g lw., respectively) and PCBs (mean of 47,168 and 628 ng/g lw., respectively)
      were the predominant compounds in both tissues. Among PCBs the highly chlorinated
      PCB 180, 153 and 138 were the predominant congeners. We found a p,p'-DDE/?DDTs
      ratio of 0.87 in blubber and 0.88 in liver, which is indicative of DDT ageing.
      All the samples showed detectable values of any of the 16 PAH studied.
      Phenanthrene was the most frequently detected and at the highest concentration.
      According to our results, concentrations of OCPs, and especially PCBs, are still
      at toxicologically relevant levels in blubber of bottlenose dolphins of this
      geographical area. 

PMID- 24726511
TI  - An assessment of contaminant concentrations in toothed whale species of the NW
      Iberian Peninsula: part I. Persistent organic pollutants.
AB  - Concentrations and patterns of polychlorinated biphenyls (PCBs) and
      polybrominated diphenyl ethers (PBDEs) in the blubber of the five most common
      toothed whales off the Northwest Iberian Peninsula (NWIP), specifically common
      dolphin, long-finned pilot whale, harbour porpoise, striped dolphin and
      bottlenose dolphin, were investigated. The study revealed that differences in PCB
      and PBDE concentrations among the species are highly dependent on age and sex but
      also on ecological factors such as trophic level, prey type and habitat. Of the
      five species studied, bottlenose dolphin and harbour porpoise showed the greatest
      concentrations of PCBs. Both species exceed the toxic threshold of 17MUgg(-1)
      lipid weight (PCB Aroclor equivalent) for health effects on marine mammals, for
      100% and 75% of the individuals tested, respectively. Overall, the PCB and PBDE
      levels observed in the NWIP toothed whales were of the same order of magnitude or
      lower than those reported by previous studies in areas of the NE Atlantic.
      However, they are often higher than those for toothed whales from the southern
      Atlantic and Pacific Ocean. 

PMID- 24726512
TI  - Dissemination of well water arsenic results to homeowners in Central Maine:
      influences on mitigation behavior and continued risks for exposure.
AB  - Private wells in the United States are unregulated for drinking water standards
      and are the homeowner's responsibility to test and treat. Testing for water
      quality parameters such as arsenic (As) is a crucial first step for homeowners to
      take protective actions. This study seeks to identify key behavioral factors
      influencing homeowners' decisions to take action after receiving well As test
      results. A January 2013 survey of central Maine households (n=386, 73% response)
      who were notified 3-7 years earlier that their well water contained As above 10
      MUg/L found that 43% of households report installing As treatment systems.
      Another 30% report taking other mitigation actions such as drinking bottled water
      because of the As, but the remaining 27% of households did not act. Well water As
      level appears to be a motivation for mitigation: 31% of households with well
      water level between 10 and 50 MUg/L did not act, compared to 11% of households
      with well water >50 MUg/L. The belief that the untreated water is not safe to
      drink (risk) and that reducing drinking water As would increase home value
      (instrumental attitude) were identified as significant predictors of mitigating
      As. Mitigating As exposure is associated with less worry about the As level
      (affective attitude), possibly because those acting to reduce exposure feel less
      worried about As. Use of a treatment system specifically was significantly
      predicted by confidence that one can maintain a treatment system, even if there
      are additional costs (self-efficacy). An assessment of As treatment systems used
      by 68 of these households with well water As >10 MUg/L followed up within August
      November 2013 found that 15% of treatment units failed to produce water below As
      10 MUg/L, suggesting that there are continued risks for exposure even after the
      decision is made to treat.

PMID- 24726513
TI  - Source of arsenic-bearing pyrite in southwestern Vermont, USA: sulfur isotope
      evidence.
AB  - Arsenic-bearing pyrite is the source of arsenic in groundwater produced in late
      Cambrian and Ordovician gray and black slates and phyllites in the Taconic region
      of southwestern Vermont, USA. The aim of this study is to analyze the sulfur
      isotopic composition of this pyrite and determine if a relationship exists
      between pyrite delta(34)S and arsenic content. Pyrite occurs in both
      sedimentary/diagenetic (bedding-parallel layers and framboids) and low-grade
      metamorphic (porphyroblast) forms, and contains up to >2000 ppm As. The sulfur
      isotopic composition of arsenic-bearing pyrite ranges from -5.20/00 to 630/00. In
      the marine environment, the sulfur in sedimentary pyrite becomes increasingly
      enriched in (34)S as the geochemical environment becomes increasingly anoxic.
      There is a positive correlation between delta(34)S and arsenic content in the
      Taconic pyrite, suggesting that uptake of arsenic by pyrite increased as the
      environment became more reducing. This increased anoxia may have been due to a
      rise in sea level and/or tectonic activity during the late Cambrian and
      Ordovician. Low-grade metamorphism appears to have little effect on sulfur
      isotope composition, but does correlate with lower arsenic content in pyrite. New
      groundwater wells drilled in this region should therefore avoid gray and black
      slates and phyllites that contain sedimentary/diagenetic pyrite with heavy
      delta(34)S values.

PMID- 24726514
TI  - Organochlorine pesticides and polychlorinated biphenyls in grass, yak muscle,
      liver, and milk in Ruoergai high altitude prairie, the eastern edge of Qinghai
      Tibet Plateau.
AB  - In highland pastures, where no agricultural and industrial activities exist,
      organochlorine pesticides (OCPs) and polychlorinated biphenyls (PCBs) are
      believed to be mainly coming from water-soil-grass system which is subject to air
      water and air-soil exchanges and atmospheric precipitation. Samples of grass and
      yak muscle, liver, and milk were measured for OCPs and PCBs in the summer and
      winter of 2011. The total concentrations of HCHs, DDTs, endosulfans, HCB, and
      PCBs in grass samples were in the range of 0.53-2.45, 1.6-6.0, 1.10-4.38, 0.30
      1.24, 0.65-2.04 ng g(-1) dw (dry weight), with the means 1.38, 2.86, 2.06, 0.73,
      and 1.19 ng g(-1) dw, respectively. The mean concentrations of HCHs and DDTs in
      yak muscle were 1.65 and 0.55 ng g(-1) fw (fresh weight), respectively; no
      significant seasonal differences. The average total concentrations of HCHs, DDTs,
      HCB, endosulfans, and PCBs in yak milk were 4.46, 0.59, 1.00, 0.27, and 0.097 ng
      g(-1) fat, respectively. Among the POPs investigated, beta-HCH and HCB were
      dominant in yak muscle and liver, whereas beta-HCH dominated the yak milk.
      Consistent with the results of other studies, PCB 153, 138, and 180 were detected
      in yak milk that is in accordance with the case reported for farmed cow milk in
      China and other countries. A human health risk was conducted based on the intake
      of OCPs via consumptions of the yak muscle and milk. Since the daily intake of
      HCHs and DDTs was lower than WHO or USEPA's acceptable daily intake or minimal
      risk level, showing that the consumptions of the yak muscle and milk would not
      pose any immediate risk to local people.

PMID- 24726515
TI  - Field-measured uptake rates of PCDDs/Fs and dl-PCBs using PUF-disk passive air
      samplers in Gyeonggi-do, South Korea.
AB  - The collection of 2,3,7,8-substituted polychlorinated dibenzo-rho-dioxins and
      dibenzo furans (PCDDs/Fs) and dioxin-like polychlorinated biphenyls (dl-PCBs)
      using a polyurethane form (PUF)-disk passive air sampler (PAS) was investigated
      in urban-residential and industrial areas. This was performed to assess the
      feasibility of using this method as an alternative to an active air sampler
      (AAS). The PUF-disk PAS was exposed to ambient air over a period of 37-370 and 57
      173 days in urban and industrial areas, respectively, together with AASs. The sum
      of total toxic equivalent quantity (TEQ) SigmaPCDDs/Fs and Sigmadl-PCB was
      typically high in the industrial area, with values within the range 0.171-0.635
      pg-TEQ/m(3), and 0.037-0.300 pg-TEQ/m(3) in the urban-residential area. To derive
      the time-weighted average (TWA) concentration from the PAS data accurately, it
      was estimated that the PAS deployed for less than 80 days was adequate to
      maintain linear accumulation conditions. PCDDs/Fs are mainly particle bound and
      showed low average uptake rates of 1.4m(3)d(-1), while dl-PCBs were slightly
      higher with 2.0m(3)d(-1) because of its high vapor pressure. Most of the congener
      concentrations measured using the PAS and AAS were within a factor of two,
      indicating that PASs can be used to monitor spatial and temporal variations in
      the concentrations of persistent organic pollutants (POPs) in the atmosphere.

PMID- 24726516
TI  - Migration of PAHs in food industry sludge to the air during removal by UV and
      TiO2.
AB  - This study was conducted to investigate the evaporation ratios of polycyclic
      aromatic hydrocarbons (PAHs) from the food industry treatment sludge. Five PAH
      compounds having different ring numbers were targeted. The effects of
      temperature, UV and TiO2 on PAH evaporation were also studied. All applications
      were performed in a specially designed apparatus. The air in the apparatus was
      vacuumed to collect the evaporated PAHs on the PUF cartridges. Then, these PUF
      cartridges were extracted for determination of PAHs. The PAH concentrations were
      measured by a gas-chromatography mass-spectrometer (GC-MS). 91% of the initial ?5
      PAHs in the sludge was evaporated into the air at the end of the UV application.
      However, this value decreased to 21% when UV was not employed. Initial and final
      PAH levels in the sludge were measured to determine the removed PAHs which refer
      to the addition of degraded and evaporated PAHs. The results indicated that the
      UV-TiO2 application at high temperatures was considered an appropriate PAH
      removal method because it restricted the evaporation of PAHs while it removed
      high levels of PAHs. PAHs were mainly removed from the sludge by degradation
      rather than evaporation with this application. 

PMID- 24726517
TI  - Impact of approach used to determine removal levels of drugs of abuse during
      wastewater treatment.
AB  - In this study the levels of 19 drugs of abuse were estimated throughout a
      wastewater treatment plant using polar organic chemical integrative samplers
      (POCIS), 24h composite samples and grab samples. Overall removal efficiencies and
      removals in between each treatment unit were calculated using load data for each
      sampling technique as well as removals that take into account the hydraulic
      residence time distribution of the treatment plant (time-shifted mass balancing
      approach). Amphetamine-type stimulants, cocaine and its major metabolite,
      benzoylecgonine and opioid levels determined with 24h composite samples were
      generally comparable to those obtained with POCIS and grab samples. Negative mass
      balances resulting from the estimation of overall removal efficiencies by POCIS,
      day-to-day mass balancing of 24h composite and grab sample data did not occur
      when the hydraulic retention time (HRT) distributions of the plant were taken
      into account for calculation. Among the compounds investigated, cocaine exhibited
      the highest overall removal (90%) while codeine had the lowest with 13%,
      respectively. Sampling between the treatment units revealed that highest removal
      occurs during biological treatment as compared to primary or secondary
      clarification. Methylenedioxyamphetamine (MDA), fentanyl, dihydrocodeine and
      heroin were not detected in wastewater at any of the sampling locations at the
      treatment plant regardless of the sampling technique. The study demonstrates the
      benefits of applying the time-shifted mass balancing approach to the calculation
      of removals of drugs of abuse during wastewater treatment. 

PMID- 24726518
TI  - PAH distribution and mass fluxes in the Three Gorges Reservoir after impoundment
      of the Three Gorges Dam.
AB  - Mass fluxes of polycyclic aromatic hydrocarbons (PAHs) were calculated for the
      Three Gorges Reservoir (TGR) in China, based on concentration and discharge data
      from the Yangtze River. Virtual Organisms (VOs) have been applied during four
      campaigns in 2008, 2009 (twice) and 2011 at sampling sites distributed from
      Chongqing to Maoping. The total PAH mass fluxes ranged from 110 to 2,160 mg s(
      1). Highest loads were determined at Chongqing with a decreasing trend towards
      Maoping in all four sampling campaigns. PAH remediation capacity of the TGR was
      found to be high as the mass flux reduced by more than half from upstream to
      downstream. Responsible processes are thought to be adsorption of PAH to
      suspended particles, dilution and degradation. Furthermore, the dependence of PAH
      concentration upon water depth was investigated at Maoping in front of the Three
      Gorges Dam. Although considerable differences could be revealed, there was no
      trend observable. Sampling of water with self-packed filter cartridges confirmed
      more homogenous PAH depth distribution. Moreover, PAH content of suspended
      particles was estimated from water concentrations gathered by VOs based on a
      water-particle separation model and subsequently compared to PAH concentration
      measured in water and in filter cartridges. It could be shown that the modeled
      data predicts the concentration caused by particle-bound PAHs to be about 6 times
      lower than PAHs dissolved in water. Besides, the model estimates the proportions
      of 5- and 6-ring PAHs being higher than in water phase.

PMID- 24726519
TI  - Sibling cannibalism in a web-building spider: effects of density and shared
      environment.
AB  - Sibling cannibalism occurs across diverse taxa and can affect population size and
      structure, as well as the fitness of parents and the cannibal, via density
      effects and variation in individual propensity to cannibalize. We examined these
      effects on sibling cannibalism in juveniles of a web-building spider (Latrodectus
      hasselti, Australian redbacks). Adult redbacks are solitary, but juveniles live
      in clusters of variable density for a week after hatching. We confined newly
      hatched siblings from a singly-mated female to a low or high density treatment in
      a split-clutch design, then left spiderlings unfed for a week. Our results showed
      no effect of density on overall cannibalism levels, but a strong correlation
      between cannibalism counts from the same maternal lines across densities. Unlike
      web-bound sit-and-wait predators, wandering spiders that are active hunters have
      been shown to experience density-dependent cannibalism. In contrast, we suggest
      sibling cannibalism in web-building spiders may be density independent because
      early cohabitation on the web selects for elevated tolerance of conspecifics. We
      conclude that, rather than being linked to density, cannibalism of siblings in
      these species may be controlled more strongly by variation in individual
      propensity to cannibalize. 

PMID- 24726520
TI  - Coactivation of the PI3K/Akt and ERK signaling pathways in PCB153-induced NF
      kappaB activation and caspase inhibition.
AB  - Polychlorinated biphenyls (PCBs) are a group of persistent and widely distributed
      environmental pollutants that have various deleterious effects, e.g.,
      neurotoxicity, endocrine disruption and reproductive abnormalities. In order to
      verify the hypothesis that the PI3K/Akt and MAPK pathways play important roles in
      hepatotoxicity induced by PCBs, Sprague-Dawley (SD) rats were dosed with PCB153
      intraperitoneally at 0, 4, 16 and 32mg/kg for five consecutive days; BRL cells
      (rat liver cell line) were treated with PCB153 (0, 1, 5, and 10MUM) for 24h.
      Results indicated that the PI3K/Akt and ERK pathways were activated in vivo and
      in vitro after exposure to PCB153, and protein levels of phospho-Akt and phospho
      ERK were significantly increased. Nuclear factor-kappaB (NF-kappaB) activation
      and caspase-3, -8 and -9 inhibition caused by PCB153 were also observed.
      Inhibiting the ERK pathway significantly attenuated PCB153-induced NF-kappaB
      activation, whereas inhibiting the PI3K/Akt pathway hardly influenced phospho-NF
      kappaB level. However, inhibiting the PI3K/Akt pathway significantly elevated
      caspase-3, -8 and -9 activities, while the ERK pathway only synergistically
      regulated caspase-9. Proliferating cell nuclear antigen (PCNA), a reliable
      indicator of cell proliferation, was also induced. Moreover, PCB153 led to
      hepatocellular hypertrophy and elevated liver weight. Taken together, PCB153
      leads to aberrant proliferation and apoptosis of hepatocytes through NF-kappaB
      activation and caspase inhibition, and coactivated PI3K/Akt and ERK pathways play
      critical roles in PCB153-induced hepatotoxicity. 

PMID- 24726521
TI  - 1,2-Dibromo-4-(1,2-dibromoethyl)-cyclohexane and tris(methylphenyl) phosphate
      cause significant effects on development, mRNA expression, and circulating bile
      acid concentrations in chicken embryos.
AB  - 1,2-Dibromo-4-(1,2-dibromoethyl)-cyclohexane (DBE-DBCH; formerly abbreviated as
      TBECH) and tris(methylphenyl) phosphate (TMPP; formerly abbreviated as TCP) are
      additive flame retardants that are detected in the environment and biota. A
      recent avian in vitro screening study of 16 flame retardants identified DBE-DBCH
      and TMPP as important chemicals for follow-up in ovo evaluation based on their
      effects on cytotoxicity and mRNA expression in avian hepatocytes. In this study,
      technical mixtures of DBE-DBCH and TMPP were injected into the air cell of
      chicken embryos at concentrations ranging from 0 to 54,900ng/g and from 0 to
      261,400ng/g, respectively, to determine effects on pipping success, development,
      hepatic mRNA expression, thyroid hormone levels, and circulating bile acid
      concentrations. Both compounds were detectable in embryos at pipping and the beta
      DBE-DBCH isomer was depleted more rapidly than the alpha-isomer in tissue
      samples. DBE-DBCH had limited effects on the endpoints measured, with the
      exception of the up-regulation of two phase I metabolizing enzymes, CYP3A37 and
      CYP2H1. TMPP exposure caused embryonic deformities, altered growth, increased
      liver somatic index (LSI) and plasma bile acid concentrations, and altered mRNA
      expression levels of genes associated with xenobiotic and lipid metabolism and
      the thyroid hormone pathway. Overall, TMPP elicited more adverse molecular and
      phenotypic effects than DBE-DBCH albeit at concentrations several orders of
      magnitude greater than those detected in the environment. The increase in plasma
      bile acid concentrations was a useful phenotypic anchor as it was associated with
      a concomitant increase in LSI, discoloration of the liver tissue, and modulation
      of hepatic genes involved with xenobiotic and lipid metabolism. 

PMID- 24726522
TI  - 2-(4-Methoxyphenyl)ethyl-2-acetamido-2-deoxy-beta-d-pyranoside confers
      neuroprotection in cell and animal models of ischemic stroke through
      calpain1/PKA/CREB-mediated induction of neuronal glucose transporter 3.
AB  - Salidroside is proven to be a neuroprotective agent of natural origin, and its
      analog, 2-(4-Methoxyphenyl)ethyl-2-acetamido-2-deoxy-beta-d-pyranoside (named
      SalA-4g), has been synthesized in our lab. In this study, we showed that SalA-4g
      promoted neuronal survival and inhibited neuronal apoptosis in primary
      hippocampal neurons exposed to oxygen and glucose deprivation (OGD) and in rats
      subjected to ischemia by transient middle cerebral artery occlusion (MCAO),
      respectively, and that SalA-4g was more neuroprotective than salidroside. We
      further found that SalA-4g elevated glucose uptake in OGD-injured primary
      hippocampal neurons and increased the expression and recruitment of glucose
      transporter 3 (GLUT3) in ischemic brain. Signaling analysis revealed that SalA-4g
      triggered the phosphorylation of CREB, and increased the expression of PKA RII in
      primary hippocampal neurons exposed to OGD injury, while inhibition of PKA/CREB
      by H-89 alleviated the elevation in glucose uptake and GLUT3 expression, and
      blocked the protective effects of SalA-4g. Moreover, SalA-4g was noted to inhibit
      intracellular Ca(2+) influx and calpain1 activation in OGD-injured primary
      hippocampal neurons. Our results suggest that SalA-4g neuroprotection might be
      mediated by increased glucose uptake and elevated GLUT3 expression through
      calpain1/PKA/CREB pathway. 

PMID- 24726523
TI  - Attenuation of Abeta25-35-induced parallel autophagic and apoptotic cell death by
      gypenoside XVII through the estrogen receptor-dependent activation of Nrf2/ARE
      pathways.
AB  - Amyloid-beta (Abeta) has a pivotal function in the pathogenesis of Alzheimer's
      disease. To investigate Abeta neurotoxicity, we used an in vitro model that
      involves Abeta25-35-induced cell death in the nerve growth factor-induced
      differentiation of PC12 cells. Abeta25-35 (20MUM) treatment for 24h caused
      apoptotic cell death, as evidenced by significant cell viability reduction, LDH
      release, phosphatidylserine externalization, mitochondrial membrane potential
      disruption, cytochrome c release, caspase-3 activation, PARP cleavage, and DNA
      fragmentation in PC12 cells. Abeta25-35 treatment led to autophagic cell death,
      as evidenced by augmented GFP-LC3 puncta, conversion of LC3-I to LC3-II, and
      increased LC3-II/LC3-I ratio. Abeta25-35 treatment induced oxidative stress, as
      evidenced by intracellular ROS accumulation and increased production of
      mitochondrial superoxide, malondialdehyde, protein carbonyl, and 8-OHdG.
      Phytoestrogens have been proved to be protective against Abeta-induced
      neurotoxicity and regarded as relatively safe targets for AD drug development.
      Gypenoside XVII (GP-17) is a novel phytoestrogen isolated from Gynostemma
      pentaphyllum or Panax notoginseng. Pretreatment with GP-17 (10MUM) for 12h
      increased estrogen response element reporter activity, activated PI3K/Akt
      pathways, inhibited GSK-3beta, induced Nrf2 nuclear translocation, augmented
      antioxidant responsive element enhancer activity, upregulated heme oxygenase 1
      (HO-1) expression and activity, and provided protective effects against Abeta25
      35-induced neurotoxicity, including oxidative stress, apoptosis, and autophagic
      cell death. In conclusion, GP-17 conferred protection against Abeta25-35-induced
      neurotoxicity through estrogen receptor-dependent activation of PI3K/Akt
      pathways, inactivation of GSK-3beta and activation of Nrf2/ARE/HO-1 pathways.
      This finding might provide novel insights into understanding the mechanism for
      neuroprotective effects of phytoestrogens or gypenosides. 

PMID- 24726524
TI  - Bleomycin-induced epithelial-mesenchymal transition in sclerotic skin of mice:
      possible role of oxidative stress in the pathogenesis.
AB  - Epithelial-mesenchymal transition (EMT) derived myofibroblasts are partly
      responsible for the increased collagen synthesis and deposition that occur in
      tissue fibrosis; however EMT occurrence in skin fibrosis and its mechanism remain
      unknown. The aim of this study was to investigate whether epithelial cells
      undergo EMT and determine the role of oxidative stress in this process. BALB/c
      mice were subcutaneously injected with bleomycin (BLM) or phosphate buffer saline
      (PBS) into the shaved back daily for 2, 3, and 4weeks. Skin collagen deposition
      was evaluated by histopathology and Western blotting. EMT characteristics in the
      skin were determined by histopathology and immunofluorescent staining for E
      cadherin and vimentin, which were further evaluated by Western blotting and
      reverse transcriptase polymerase chain reaction (RT-PCR). To investigate the role
      of oxidative stress in EMT, the antioxidant N-acetylcysteine (NAC) was
      intraperitoneally (100mg/kg body weight/day) injected daily for 3weeks. The
      epithelial suprabasal cells were detached from the basement membrane zone (BMZ)
      in the sclerotic skin treated with BLM. Immunofluorescent staining indicated
      vimentin-positive epithelial cells frequently occurring in the thickened
      epidermis of BLM-treated mice. Western blotting and RT-PCR showed that the
      expression of E-cadherin was significantly decreased but that of vimentin
      significantly increased in the skin treated with BLM. NAC attenuated BLM induced
      oxidative damage, changes in E-cadherin and vimentin expressions and collagen
      deposition in the sclerotic skin of mice. This study provides the first evidence
      that BLM induces the EMT of the epithelial cells superficial to the basement
      membrane zone in the skin fibrosis. Oxidative stress may contribute, at least in
      part, to BLM induced EMT and skin fibrosis in mice. 

PMID- 24726526
TI  - Protease inhibitors and avascular necrosis: a systematic review and meta
      analysis.
AB  - Avascular necrosis (AVN) is a pathological process associated with many medical
      conditions, including human immunodeficiency virus (HIV) infection. Whether or
      not the use of protease inhibitors (PIs) confers additional risk for AVN to HIV
      infected patients is controversial. Previous epidemiological studies showed an
      increased risk of AVN among PI users, but these studies did not have enough power
      to achieve statistical significance. A meta-analysis of case-control studies
      reporting the odds ratios (ORs) of AVN among HIV-infected patients who were
      exposed to PIs compared with non-exposed patients was conducted. Pooled ORs and
      95% confidence intervals (CIs) were calculated using a fixed-effect Mantel
      Haenszel analysis. Four case-control studies were identified and included for
      data analysis. The meta-analysis demonstrated an increased odds of AVN in
      participants exposed to PIs, with an OR of 2.09 (95% CI 1.01-4.31; P=0.05). The
      statistical heterogeneity of this meta-analysis was determined not to be
      important, with an I(2) of 0%. The meta-analysis revealed a statistically
      significant increased odds of AVN among PI-exposed, HIV-infected patients.
      Physician should be aware of this association as it may help guide potential
      therapeutic options, particularly for patients with other classic risk factors
      for AVN. 

PMID- 24726525
TI  - Peroxisomal membrane channel Pxmp2 in the mammary fat pad is essential for
      stromal lipid homeostasis and for development of mammary gland epithelium in
      mice.
AB  - To understand the functional role of the peroxisomal membrane channel Pxmp2, mice
      with a targeted disruption of the Pxmp2 gene were generated. These mice were
      viable, grew and bred normally. However, Pxmp2(-/-) female mice were unable to
      nurse their pups. Lactating mammary gland epithelium displayed secretory lipid
      droplets and milk proteins, but the size of the ductal system was greatly
      reduced. Examination of mammary gland development revealed that retarded mammary
      ductal outgrowth was due to reduced proliferation of epithelial cells during
      puberty. Transplantation experiments established the Pxmp2(-/-) mammary stroma as
      a tissue responsible for suppression of epithelial growth. Morphological and
      biochemical examination confirmed the presence of peroxisomes in the mammary fat
      pad adipocytes, and functional Pxmp2 was detected in the stroma of wild-type
      mammary glands. Deletion of Pxmp2 led to an elevation in the expression of
      peroxisomal proteins in the mammary fat pad but not in liver or kidney of
      transgenic mice. Lipidomics of Pxmp2(-/-)mammary fat pad showed a decrease in the
      content of myristic acid (C14), a principal substrate for protein myristoylation
      and a potential peroxisomal beta-oxidation product. Analysis of complex lipids
      revealed a reduced concentration of a variety of diacylglycerols and
      phospholipids containing mostly polyunsaturated fatty acids that may be caused by
      activation of lipid peroxidation. However, an antioxidant-containing diet did not
      stimulate mammary epithelial proliferation in Pxmp2(-/-) mice. The results point
      to disturbances of lipid metabolism in the mammary fat pad that in turn may
      result in abnormal epithelial growth. The work reveals impaired mammary gland
      development as a new category of peroxisomal disorders.

PMID- 24726527
TI  - Traversing psychological distance.
AB  - Traversing psychological distance involves going beyond direct experience, and
      includes planning, perspective taking, and contemplating counterfactuals.
      Consistent with this view, temporal, spatial, and social distances as well as
      hypotheticality are associated, affect each other, and are inferred from one
      another. Moreover, traversing all distances involves the use of abstraction,
      which we define as forming a belief about the substitutability for a specific
      purpose of subjectively distinct objects. Indeed, across many instances of both
      abstraction and psychological distancing, more abstract constructs are used for
      more distal objects. Here, we describe the implications of this relation for
      prediction, choice, communication, negotiation, and self-control. We ask whether
      traversing distance is a general mental ability and whether distance should
      replace expectancy in expected-utility theories. 

PMID- 24726528
TI  - Structural functional and folding scenario of an anti platelet and thrombolytic
      enzyme crinumin.
AB  - A folding pattern, conformational stability and therapeutic role of a protein
      helps in developing a suitable drug. Crinumin, a thrombolytic and anti platelet
      agent, has been studied for its functional and conformational properties by
      equilibrium unfolding methods. The crinumin belongs to alpha+beta class of
      protein and exhibits a non native structure and two molten globule states at
      different conditions. Two domains in the molecular structure of the protein with
      altered stability are present that unfold sequentially. The enzyme maintains
      activity as well as structural integrity even in adverse conditions. These
      observations provide an understanding of protein folding as well as facilitate
      the development of a potential drug. 

PMID- 24726529
TI  - Interaction of arabinogalactan with mucins.
AB  - Arabinogalactan is a naturally-occurring, densely branched, polysaccharide mainly
      made-up of galactose and arabinose with variable amounts of uronic acids, which
      received attention for several industrial and biomedical applications. The
      ability of Western Larch arabinogalactan to interact with mucins was assessed by
      both classical gel filtration chromatography and frontal chromatography on
      Sephacryl S300 resin. The shift of arabinogalactan elution volume in classical
      gel filtration chromatography induced by both bovine submaxillary mucin and
      porcine gastric mucin resulted useful for revealing the occurrence of an
      interaction between arabinogalactan and mucins. A frontal gel chromatography, in
      which arabinogalactan is used as eluent, enabled a dissociation constant of 5*10(
      6)M to be measured for the arabinogalactan-bovine submaxillary mucin complex,
      with approximately 50 equivalents of arabinogalactan bound per mucin mole. The
      mucoadhesivity of arabinogalactan may be a relevant feature for its biomedical
      and industrial applications. 

PMID- 24726530
TI  - Micro-structural, linear and nonlinear optical properties of titania
      nanoparticles.
AB  - TiO(2) (titania) nanoparticles were prepared by sol-gel method using titanium
      tetrachloride as precursor and calcined at 500 degrees C (SA1) and 800 degrees C
      (SA2). X-ray diffraction pattern of SA1 has mixed phases of anatase (17%) and
      rutile (83%) whereas SA2 has pure rutile (100%) TiO(2). From the X-ray
      diffraction peak profile analysis, the crystallite size, lattice strain,
      deformation stress and energy density value of TiO(2)nanoparticles were
      determined more precisely by Williamson-Hall method, uniform deformation model,
      uniform stress deformation model, uniform deformation energy density model and
      size-strain plot method. The calculated average crystallite size from uniform
      stress deformation model is 21 and 53nm for SA1 and SA2 respectively. From the
      FTIR spectra Ti-O vibrational frequency is observed at ~530cm(-1). Using Tauc's
      relation the direct bandgap of SA1 and SA2 is calculated from UV-vis spectra as
      2.75 and 2.95eV respectively. The excitation wavelength dependent
      photoluminescence has been investigated for 290 and 330nm as excitation
      wavelengths. It was observed that the band edge emission is decreased with
      respect to excitation wavelengths. The second harmonic generation efficiency
      (SHG) observed for centrosymmetric rutile TiO(2) is more comparable with KDP
      crystal.

PMID- 24726531
TI  - Detection of new psychoactive substance use among emergency room patients:
      results from the Swedish STRIDA project.
AB  - The "STRIDA" project monitors the occurrence and trends of new psychoactive
      substances (NPS; "Internet drugs/designer drugs/legal highs") in Sweden, and
      collects information about their clinical symptoms, toxicity and associated
      health hazards. The initial results of the project documented a widespread use of
      many different NPS by mainly adolescents and young (age range 13-63 years, median
      20), male (79%) adults, among cases of drug intoxications presenting at emergency
      departments and intensive care units across the country. The new substances were
      identified in samples of urine and blood by a multi-component LC-MS/MS method,
      and the severity of clinical symptoms were graded by the Poisoning Severity Score
      (PSS). Of the initial 189 samples submitted for laboratory investigation, 156
      (83%) tested positive for at least one drug. Besides classical substances such as
      ethanol, cannabis and amphetamines, many NPS were detected comprising synthetic
      cannabinoid receptor agonists ("Spice"), piperazines, substituted
      phenethylamines, synthetic cathinones, hallucinogenic tryptamines, piperidines,
      opioid related substances, ketamine and related substances, and GABA analogues
      (in total more than 50 substances). About half of the cases were demonstrated to
      be multiple drug intoxications, sometimes making it hard to associate the
      clinical presentations with one specific substance. In conclusion, the STRIDA
      project has documented use of a broad variety of NPS among mainly young people
      all over Sweden. 

PMID- 24726532
TI  - How important are seabirds in the diet of black rats on islands with a
      superpredator?
AB  - This study assessed the impact of introduced black rats (Rattus rattus) on Cory's
      shearwater (Calonectris diomedea borealis) in a multi-invaded insular ecosystem
      where rats are mesopredators. We hypothesized that black rats should have little
      impact on Cory's shearwaters in the presence of cats as superpredators. Stomach
      contents and stable isotope analysis (SIA) in tissues of black rats were analyzed
      to assess the trophic ecology and the importance of Cory's shearwater in their
      diet. We also studied the isotopic signature in tissues of house mouse (Mus
      domesticus) to confirm previous data showing no predation of this species on
      Cory's shearwaters. For both rodent species, temporal variation in diet
      composition in response to the availability of seabird prey was evaluated, and
      short- and long-term consistency in diet was tested using different tissues from
      the same individual. For black rats a Bayesian isotope mixing model (SIAR) was
      applied to determine the relative contribution of each prey to the individual
      diet. SIA of mouse tissues varied between the Cory's shearwater breeding and non
      breeding periods. However, no significant differences were found in diet and SIA
      for black rats. In contrast, individuals of both species showed a strong
      consistency in diet which apparently benefited their body condition index.
      Although black rats supplement their diet with Cory's shearwater eggs and chicks
      (8.3% in stomach contents and 10.6% in the SIAR model), their current impact on
      the Cory's shearwater population appears to be small, probably due to several
      factors including the small size of the rat population and a high level of rat
      predation by cats.

PMID- 24726533
TI  - The state of the art in European research on reducing social exclusion and stigma
      related to mental health: a systematic mapping of the literature.
AB  - Stigma and social exclusion related to mental health are of substantial public
      health importance for Europe. As part of ROAMER (ROAdmap for MEntal health
      Research in Europe), we used systematic mapping techniques to describe the
      current state of research on stigma and social exclusion across Europe. Findings
      demonstrate growing interest in this field between 2007 and 2012. Most studies
      were descriptive (60%), focused on adults of working age (60%) and were performed
      in Northwest Europe-primarily in the UK (32%), Finland (8%), Sweden (8%) and
      Germany (7%). In terms of mental health characteristics, the largest proportion
      of studies investigated general mental health (20%), common mental disorders
      (16%), schizophrenia (16%) or depression (14%). There is a paucity of research
      looking at mechanisms to reduce stigma and promote social inclusion, or at
      factors that might promote resilience or protect against stigma/social exclusion
      across the life course. Evidence is also limited in relation to evaluations of
      interventions. Increasing incentives for cross-country research collaborations,
      especially with new EU Member States and collaboration across European
      professional organizations and disciplines, could improve understanding of the
      range of underpinning social and cultural factors which promote inclusion or
      contribute toward lower levels of stigma, especially during times of hardship.

PMID- 24726534
TI  - Characterizing early detection of language difficulties in children born preterm.
AB  - BACKGROUND: The optimal age for assessing language difficulties in premature
      children remains unclear. AIMS: To determine the most predictive and earliest
      screening tool for later language difficulties on children born preterm. STUDY
      DESIGN: A prospective population-based study in the Loire Infant Follow-up Team
      LIFT SUBJECTS: All children born <35weeks of gestation between 2003 and 2005 were
      assessed at corrected ages by four screening tools: the Ages & Stages
      Questionnaire (ASQ) communication scale at 18 and 24months, the language items of
      Brunet Lezine test at 24months, and the "Epreuves de Reperage des Troubles du
      Langage" (ERTL) at 4years. OUTCOME MEASURES: After 5years, the kindergarten
      teacher evaluated the vocabulary, grammar and pronunciation capacities of the
      child in comparison with the classroom performances. RESULTS: Among 1957 infants
      enrolled at discharge, 947 were assessed by their teacher with 12.2% (n=116) of
      language difficulties. Full data at all time points were available for 426
      infants. The area under curve of the receiver operator characteristic curve
      obtained for the ASQ communication scale at 18months was significantly lower
      (0.65+/-0.09) than that obtained at 24months (0.77+/-0.08) and the languages
      items of Brunet Lezine test at 24months (0.77+/-0.08), and the ERTL at 4years
      (0.76+/-0.09). The optimal cut-off value for ASQ communication at 24months is
      <=45 [sensitivity of 0.79 (95%CI: 0.70-0.86); specificity of 0.63 (95%CI: 0.59
      0.66)]. CONCLUSIONS: The Ages & Stages Questionnaire communication scale at 24
      corrected months appears as an acceptable test at an early time point to identify
      preterm children at risk of later language difficulties.

PMID- 24726535
TI  - Ultrasmall superparamagnetic iron oxide nanoparticle prelabelling of human neural
      precursor cells.
AB  - Stem cells prelabelled with iron oxide nanoparticles can be visualised using
      magnetic resonance imaging (MRI). This technique allows for noninvasive long-term
      monitoring of migration, integration and stem cell fate following transplantation
      into living animals. In order to determine biocompatibility, the present study
      investigated the biological impact of introducing ultrasmall superparamagnetic
      iron oxide nanoparticles (USPIOs) into primary human fetal neural precursor cells
      (hNPCs) in vitro. USPIOs with a mean diameter of 10-15 nm maghemite iron oxide
      core were sterically stabilised by 95% methoxy-poly(ethylene glycol) (MPEG) and
      either 5% cationic (NH2) end-functionalised, or 5% Rhodamine B end
      functionalised, polyacrylamide. The stabilising polymer diblocks were synthesised
      by reversible addition-fragmentation chain transfer (RAFT) polymerisation. Upon
      loading, cellular viability, total iron capacity, differentiation, average
      distance of migration and changes in intracellular calcium ion concentration were
      measured to determine optimal loading conditions. Taken together we demonstrate
      that prelabelling of hNPCs with USPIOs has no significant detrimental effect on
      cell biology and that USPIOs, when utilised at an optimised dosage, are an
      effective means of noninvasively tracking prelabelled hNPCs. 

PMID- 24726537
TI  - Sorafenib resistance and JNK signaling in carcinoma during extracellular matrix
      stiffening.
AB  - Tumor progression is coincident with mechanochemical changes in the extracellular
      matrix (ECM). We hypothesized that tumor stroma stiffening, alongside a shift in
      the ECM composition from a basement membrane-like microenvironment toward a dense
      network of collagen-rich fibers during tumorigenesis, confers resistance to
      otherwise powerful chemotherapeutics. To test this hypothesis, we created a high
      throughput drug screening platform based on our poly(ethylene glycol)
      phosphorylcholine (PEG-PC) hydrogel system, and customized it to capture the
      stiffness and integrin-binding profile of in vivo tumors. We report that the
      efficacy of a Raf kinase inhibitor, sorafenib, is reduced on stiff, collagen-rich
      microenvironments, independent of ROCK activity. Instead, sustained activation of
      JNK mediated this resistance, and combining a JNK inhibitor with sorafenib
      eliminated stiffness-mediated resistance in triple negative breast cancer cells.
      Surprisingly, neither ERK nor p38 appears to mediate sorafenib resistance, and
      instead, either ERK or p38 inhibition rescued sorafenib resistance during JNK
      inhibition, suggesting negative crosstalk between these signaling pathways on
      stiff, collagen-rich environments. Overall, we discovered that beta1 integrin and
      its downstream effector JNK mediate sorafenib resistance during tumor stiffening.
      These results also highlight the need for more advanced cell culture platforms,
      such as our high-throughput PEG-PC system, with which to screen
      chemotherapeutics. 

PMID- 24726536
TI  - Bone regeneration using an alpha 2 beta 1 integrin-specific hydrogel as a BMP-2
      delivery vehicle.
AB  - Non-healing bone defects present tremendous socioeconomic costs. Although
      successful in some clinical settings, bone morphogenetic protein (BMP) therapies
      require supraphysiological dose delivery for bone repair, raising treatment costs
      and risks of complications. We engineered a protease-degradable poly(ethylene
      glycol) (PEG) synthetic hydrogel functionalized with a triple helical,
      alpha2beta1 integrin-specific peptide (GFOGER) as a BMP-2 delivery vehicle.
      GFOGER-functionalized hydrogels lacking BMP-2 directed human stem cell
      differentiation and produced significant enhancements in bone repair within a
      critical-sized bone defect compared to RGD hydrogels or empty defects. GFOGER
      functionalization was crucial to the BMP-2-dependent healing response.
      Importantly, these engineered hydrogels outperformed the current clinical carrier
      in repairing non-healing bone defects at low BMP-2 doses. GFOGER hydrogels
      provided sustained in vivo release of encapsulated BMP-2, increased
      osteoprogenitor localization in the defect site, enhanced bone formation and
      induced defect bridging and mechanically robust healing at low BMP-2 doses which
      stimulated almost no bone regeneration when delivered from collagen sponges.
      These findings demonstrate that GFOGER hydrogels promote bone regeneration in
      challenging defects with low delivered BMP-2 doses and represent an effective
      delivery vehicle for protein therapeutics with translational potential. 

PMID- 24726538
TI  - Osseointegration of dental implants in 3D-printed synthetic onlay grafts
      customized according to bone metabolic activity in recipient site.
AB  - Onlay grafts made of monolithic microporous monetite bioresorbable bioceramics
      have the capacity to conduct bone augmentation. However, there is heterogeneity
      in the graft behaviour in vivo that seems to correlate with the host anatomy. In
      this study, we sought to investigate the metabolic activity of the regenerated
      bone in monolithic monetite onlays by using positron emission tomography-computed
      tomography (PET-CT) in rats. This information was used to optimize the design of
      monetite onlays with different macroporous architecture that were then fabricated
      using a 3D-printing technique. In vivo, bone augmentation was attempted with
      these customized onlays in rabbits. PET-CT findings demonstrated that bone
      metabolism in the calvarial bone showed higher activity in the inferior and
      lateral areas of the onlays. Histological observations revealed higher bone
      volume (up to 47%), less heterogeneity and more implant osseointegration (up to
      38%) in the augmented bone with the customized monetite onlays. Our results
      demonstrated for the first time that it is possible to achieve osseointegration
      of dental implants in bone augmented with 3D-printed synthetic onlays. It was
      also observed that designing the macropore geometry according to the bone
      metabolic activity was a key parameter in increasing the volume of bone augmented
      within monetite onlays. 

PMID- 24726539
TI  - Conditions of lateral surface confinement that promote tissue-cell integration
      and inhibit biofilm growth.
AB  - Surfaces with cell adhesiveness modulated at micro length scales can exploit
      differences between tissue/bacterial cell size, membrane/wall plasticity, and
      adhesion mechanisms to differentially control tissue-cell/material and
      bacteria/material interactions. This study explores the short-term interactions
      of Staphylococcus aureus and osteoblast-like cells with surfaces consisting of
      cell-adhesive circular patches (1-5 MUm diameter) separated by non-adhesive
      electron-beam patterned poly(ethylene glycol) hydrogel thin films at inter-patch
      distances of 0.5-10 MUm. Osteoblast-like U2OS cells both bind to and spread on
      the modulated surfaces, in some cases when the cell-adhesive area comprises only
      9% of the total surface and in several cases at least as well as on the
      continuously adhesive control surfaces. In contrast, S. aureus adhesion rates are
      7-20 times less on the modulated surfaces than on the control surfaces.
      Furthermore, the proliferation of those bacteria that do adhere is inhibited by
      the lateral confinement imposed by the non-adhesive boundaries surrounding each
      patch. These findings suggest a new approach to create biomaterial surfaces that
      may promote healing while simultaneously reducing the probability of infection. 

PMID- 24726540
TI  - Severe neonatal hyperbilirubinemia and UGT1A1 promoter polymorphism.
AB  - OBJECTIVE: To assess whether UGT1A1 promoter polymorphisms associated with
      Gilbert Syndrome (GS) occur with a greater frequency in neonates with severe
      hyperbilirubinemia. STUDY DESIGN: In a case-control study performed at a single
      hospital center in Italy, 70 case subjects with severe hyperbilirubinemia
      (defined as bilirubin level >=20 mg/dL or 340 MUmol/L) and 70 controls (bilirubin
      level <12 mg/dL or 210 MUmol/L) were enrolled. Both case and control subjects
      were full term newborns. Polymerase chain reaction analysis on blood spot was
      performed to determine the frequency of UGTA1A1 promoter polymorphisms in cases
      and controls. RESULTS: No statistical difference in the prevalence of UGTA1A1
      gene variants was found between cases and controls (P = 1). Thirteen infants
      homozygous for (TA)7 polymorphism associated with GS were in the case group
      (18.6%) and 14 in the control group (20.0%). A heterozygous group was also
      equally distributed between cases (44.3%) and controls (42.9%). No (TA)8 repeat
      was found in the 2 groups. CONCLUSIONS: In our study population, GS polymorphism
      alone does not appear to play a major role in severe neonatal hyperbilirubinemia
      in neonates without signs of hemolysis.

PMID- 24726541
TI  - Relationship of gastrointestinal symptoms and psychosocial distress to gastric
      retention in children.
AB  - OBJECTIVES: To determine whether gastrointestinal (GI) symptoms (abdominal pain,
      nonpain GI symptoms, nausea) and/or psychosocial distress differ between children
      with/without gastroparesis and whether the severity of GI symptoms and/or
      psychosocial distress is related to the degree of gastroparesis. STUDY DESIGN:
      Children aged 7-18 years (N = 100; 63 female patients) undergoing a 4-hour
      gastric emptying scintigraphy study completed questionnaires evaluating GI
      symptoms, anxiety, and somatization for this prospective study. Spearman
      correlation, Mann-Whitney, t-test, and chi(2) tests were used as appropriate for
      statistical analysis. RESULTS: Children with gastroparesis (n = 25) were younger
      than those with normal emptying (12.6 +/- 3.5 vs 14.3 +/- 2.6 years, P = .01).
      Because questionnaire responses from 7- to 10-year-old children were
      inconsistent, only patient-reported symptoms from 11- to 18-year-olds were used.
      Within this older group (n = 83), children with gastroparesis (n = 17) did not
      differ from children with normal emptying in severity of GI symptoms or
      psychosocial distress. In children with gastroparesis, gastric retention at 4
      hours was related inversely to vomiting (r = -0.506, P = .038), nausea (r = 
      0.536, P = .019), difficulty finishing a meal (r = -0.582, P = .014), and
      Children's Somatization Inventory score (r = -0.544, P = .024) and positively
      correlated with frequency of waking from sleep with symptoms (r = 0.551, P =
      .022). CONCLUSIONS: The severity of GI symptoms and psychosocial distress do not
      differ between children with/without gastroparesis who are undergoing gastric
      emptying scintigraphy. In those with gastroparesis, gastric retention appears to
      be inversely related to dyspeptic symptoms and somatization and positively
      related to waking from sleep with symptoms.

PMID- 24726542
TI  - Trade-off between lower or higher oxygen saturations for extremely preterm
      infants: the first benefits of oxygen saturation targeting (BOOST) II trial
      reports its primary outcome.

PMID- 24726543
TI  - Skeletal surveys and head computed tomographies in the evaluation of child abuse:
      refining practice patterns.

PMID- 24726544
TI  - Maintenance fluid therapy: what's next.

PMID- 24726545
TI  - A 5-year-old with connective tissue nevi: Buschke-Ollendorff syndrome.

PMID- 24726546
TI  - Wood and humus decay strategies by white-rot basidiomycetes correlate with two
      different dye decolorization and enzyme secretion patterns on agar plates.
AB  - During several forays for ligninolytic fungi in different Spanish native forests,
      35 white-rot basidiomycetes growing on dead wood (16 species from 12 genera) and
      leaf litter (19 species from 10 genera) were selected for their ability to
      decolorize two recalcitrant aromatic dyes (Reactive Blue 38 and Reactive Black 5)
      added to malt extract agar medium. In this study, two dye decolorization patterns
      were observed and correlated with two ecophysiological groups (wood and humus
      white-rot basidiomycetes) and three taxonomical groups (orders Polyporales,
      Hymenochaetales and Agaricales). Depending on the above groups, different
      decolorization zones were observed on the dye-containing plates, being restricted
      to the colony area or extending to the surrounding medium, which suggested two
      different decay strategies. These two strategies were related to the ability to
      secrete peroxidases and laccases inside (white-rot wood Polyporales,
      Hymenochaetales and Agaricales) and outside (white-rot humus Agaricales) of the
      fungal colony, as revealed by enzymatic tests performed directly on the agar
      plates. Similar oxidoreductases production patterns were observed when fungi were
      grown in the absence of dyes, although the set of enzyme released was different.
      All these results suggest that the decolorization patterns observed could be
      related with the existence of two decay strategies developed by white-rot
      basidiomycetes adapted to wood and leaf litter decay in the field. 

PMID- 24726547
TI  - The role of initial neck dissection for patients with node-positive oropharyngeal
      squamous cell carcinomas.
AB  - BACKGROUND: The current study sought to assess the role of initial neck
      dissection (ND) for patients with node-positive oropharyngeal squamous cell
      carcinomas (OPSCC). METHODS: The data for 202 patients with previously untreated
      node-positive OPSCC were gathered from 12 institutions belonging to the Head and
      Neck Cancer Study Group in the Japan Clinical Oncology Group. These patients were
      categorized into two groups, consisting of the initial ND group and the wait-and
      see group, according to treatment policy. RESULTS: Regional recurrence was
      observed in 17 of 93 patients undergoing initial ND, whereas, recurrent or
      persistent diseases were observed in 40 of 109 patients who did not undergo
      initial ND. The 4-year overall survival rates (OS) for the wait-and-see group and
      initial ND groups were 74.0% and 78.7%, respectively, and the 4-year regional
      control rates (RC) for each group were 77.6% and 84.9%. There were no significant
      differences in either OS or RC (p=0.3440 and p=0.2382, respectively). However,
      for patients with N3 disease, the 4-year OS of the initial ND group (100%) was
      favorable. For patients with N2a disease, the 4-year RC of the initial ND group
      was higher than that of the wait-and-see group statistically (100% vs 62.5%,
      p=0.0156). CONCLUSIONS: The role of initial ND was limited in patients with node
      positive OPSCC. The treatment strategy not involving initial ND is considered
      feasible and acceptable when nodal evaluation after definitive radiotherapy or
      chemoradiotherapy is applied adequately. However, it is possible that initial ND
      improves outcomes in patients with resectable large-volume nodal disease.

PMID- 24726548
TI  - Intertypic modular exchanges of genomic segments by homologous recombination at
      universally conserved segments in human adenovirus species D.
AB  - Human adenovirus species D (HAdV-D), which is composed of clinically and
      epidemiologically important pathogens worldwide, contains more taxonomic "types"
      than any other species of the genus Mastadenovirus, although the mechanisms
      accounting for the high level of diversity remain to be disclosed. Recent studies
      of known and new types of HAdV-D have indicated that intertypic recombination
      between distant types contributes to the increasing diversity of the species.
      However, such findings raise the question as to how homologous recombination
      events occur between diversified types since homologous recombination is
      suppressed as nucleotide sequences diverge. In order to address this question, we
      investigated the distribution of the recombination boundaries in comparison with
      the landscape of intergenomic sequence conservation assessed according to the
      synonymous substitution rate (dS). The results revealed that specific genomic
      segments are conserved between even the most distantly related genomes; we call
      these segments "universally conserved segments" (UCSs). These findings suggest
      that UCSs facilitate homologous recombination, resulting in intergenomic
      segmental exchanges of UCS-flanking genomic regions as recombination modules.
      With the aid of such a mechanism, the haploid genomes of HAdV-Ds may have been
      reshuffled, resulting in chimeric genomes out of diversified repertoires in the
      HAdV-D population analogous to the MHC region reshuffled via crossing over in
      vertebrates. In addition, some HAdVs with chimeric genomes may have had the
      opportunity to avoid host immune responses thereby causing epidemics. 

PMID- 24726549
TI  - Expression profiling and ontology analysis of long noncoding RNAs in post
      ischemic heart and their implied roles in ischemia/reperfusion injury.
AB  - Long noncoding RNAs (lncRNAs) play important regulatory roles in cellular
      physiology. The contributions of lncRNAs to ischemic heart disease remain largely
      unknown. The aim of this study was to investigate the profile of myocardial
      lncRNAs and their potential roles at early stage of reperfusion. lncRNAs and
      mRNAs were profiled by microarray and the expression of some highly-dysregulated
      lncRNAs was further validated using polymerase chain reaction. Our results
      revealed that 64 lncRNAs were up-regulated and 87 down-regulated, while 50 mRNAs
      were up-regulated and 60 down-regulated in infarct region at all reperfusion
      sampled. Gene ontology analysis indicated that dysregulated transcripts were
      associated with immune response, spermine catabolic process, taxis, chemotaxis,
      polyamine catabolic process, spermine metabolic process, chemokine activity and
      chemokine receptor binding. Target gene-related pathway analysis showed
      significant changes in cytokine-cytokine receptor interaction, the chemokine
      signaling pathway and nucleotide oligomerization domain (NOD)-like receptor
      signaling pathway which have a close relationship with myocardial
      ischemia/reperfusion injury (MI/RI). Besides, a gene co-expression network was
      constructed to identify correlated targets of 10 highly-dysregulated lncRNAs.
      These lncRNAs may play their roles by this network in post-ischemic heart. Such
      results provide a foundation for understanding the roles and mechanisms of
      myocardial lncRNAs at early stage of reperfusion. 

PMID- 24726550
TI  - Investigation of JAK1 and STAT3 polymorphisms and their gene-gene interactions in
      nonspecific digestive disorder of rabbits.
AB  - Acting in a cellular signaling pathway, Janus kinase 1 (JAK1) and signal
      transducer and activator of transcription 3 (STAT3) play critical roles in
      several kinds of physiological and pathological responses, including inflammatory
      response. In this study, we detected three coding single nucleotide polymorphisms
      (cSNPs) of JAK1 and four cSNPs of STAT3 in New Zealand White rabbits. We analyzed
      their association with genetic resistance to nonspecific digestive disorder
      (NSDD) based on a case-control study (253 cases and 227 controls). The rabbits
      were genotyped for c.1421 C>T and c.3036 G>A in JAK1 using restriction fragment
      length polymorphisms and for c.831 T>C and c.399 G>A of STAT3 using high
      resolution melting technology. The frequencies of the alleles and genotypes
      differed significantly between the case and control groups (P<0.05). The case
      control association analysis revealed that in JAK1, allele C increased the risk
      of NSDD (OR: 1.60, 95% CI 1.166-2.185, P=0.003), whereas allele A played a
      potentially protective role against NSDD (OR: 0.74, 95% CI 0.572-0.952, P=0.019).
      We used five inheritance models to evaluate the importance of the associated
      genotypes. Under the dominant inheritance model, the association analysis
      suggested that the CT/TT genotype increased the risk of NSDD (OR: 1.65, 95% CI
      1.13-2.40, P=0.009). A haplotype analysis showed that allele H2 (the two cSNPs:
      CG; OR: 1.354, 95% CI 1.050-1.747, P=0.019) markedly increased the risk of the
      disorder. The association analysis revealed that in STAT3, allele G played a
      potentially protective role against NSDD (OR: 0.74; 95% CI 0.569-0.951; P=0.019),
      whereas allele C increased the risk of NSDD (OR: 1.37; 95% CI 1.059-1.760;
      P=0.016). Recessive inheritance was shown to be the best fitting model for c.399
      and c.831. Under the recessive inheritance model, the association analysis
      suggested that the G/G genotype increased the risk of NSDD (OR: 1.73; 95% CI 1.07
      2.80; P=0.025). A haplotype analysis showed that H1' (the two cSNPs: AC; OR:
      1.365; CI 1.059-1.760; P=0.016) significantly increased the risk of the disorder.
      The CATMOD program (SAS 9.2) and the multifactor dimensionality reduction method
      were used to analyze the genetic interactions between JAK1 and STAT3. Data on the
      genetic interactions revealed that the JAK1 and STAT3 risk alleles described
      above contribute to NSDD susceptibility in combination with each other, and that
      model (c1421, c3036, c831) was the best model (OR: 2.7262; 95% CI: 4.7408-5.1986;
      P<0.0001). To our knowledge, this is the first report of the genetic
      polymorphisms of the JAK1 and STAT3 genes and their associations with the
      incidence of NSDD in rabbits. 

PMID- 24726551
TI  - Molecular cloning, characterization, and expression analysis of a heat shock
      protein (HSP) 70 gene from Paphia undulata.
AB  - In this study, a full-length HSP70 cDNA from Paphia undulata was cloned using
      reverse transcriptase polymerase chain reaction (RT-PCR) coupled with rapid
      amplification of cDNA ends (RACE). The full-length cDNA is 2,351 bp, consisting
      of a 5'-untranslated region (UTR) of 83 bp, a 3'-UTR of 315 bp, and an open
      reading frame (ORF) of 1,953 bp. This cDNA encodes 650 amino acids with an
      estimated molecular weight of 71.3 kDa and an isoelectric point of 5.51. Based on
      the amino acid sequence analysis and phylogenetic analysis, this HSP70 gene was
      identified as a member of the cytoplasmic HSP70 family, being the constitutive
      expression, and it was designated as PuHSC70. The distribution of PuHSC70 mRNA in
      the mantle, digestive gland, adductor muscle, gonad, gill, heart, and hemocytes
      suggested that PuHSC70 is ubiquitously expressed. The mRNA levels of PuHSC70
      under high temperature and high salinity stresses were analyzed by real-time PCR.
      Under high temperature stress of 32 degrees C, PuHSC70 mRNA in the mantle,
      digestive gland, gill, and heart was significantly up-regulated at 1h and 2h, and
      it was then progressively down-regulated. In the adductor muscle, the level of
      PuHSC70 mRNA gradually increased throughout the study period; the mRNA levels in
      the gonad and hemocytes increased significantly at 4h and 8h (P<0.05) and then
      decreased at 8h and 14 h, respectively, however they increased again afterwards,
      reaching the highest levels at 50h. Under high salinity (32 0/00) stress, the
      mRNA levels of PuHSC70 in the mantle and gonad were increased significantly only
      at 24h and 48 h (P<0.05), and at the rest of the study period they were slightly
      elevated. Compared with the pretreatment level, the levels of expression in the
      digestive gland and gill were unchanged or reduced throughout the study period.
      The levels of PuHSC70 mRNA in the adductor muscle, hemocytes, and heart were
      significantly increased, reaching a maximum at 24h, and then they gradually
      decreased; moreover, in the heart, the mRNA expression recovered to the
      pretreatment level at 50h; while in the adductor muscle and hemocytes, the
      expression level remained higher than that of the control. The cloning and
      expression analyses of PuHSC70 provide theoretical basis to further study the
      mechanism of physiological response to thermal and high salinity stresses.

PMID- 24726552
TI  - Radionuclide release from simulated waste material after biogeochemical leaching
      of uraniferous mineral samples.
AB  - Biogeochemical mineral dissolution is a promising method for the released of
      metals in low-grade host mineralization that contain sulphidic minerals. The
      application of biogeochemical mineral dissolution to engineered leach heap piles
      in the Elliot Lake region may be considered as a promising passive technology for
      the economic recovery of low grade Uranium-bearing ores. In the current
      investigation, the decrease of radiological activity of uraniferous mineral
      material after biogeochemical mineral dissolution is quantified by gamma
      spectroscopy and compared to the results from digestion/ICP-MS analysis of the
      ore materials to determine if gamma spectroscopy is a simple, viable alternative
      quantification method for heavy nuclides. The potential release of Uranium (U)
      and Radium-226 ((226)Ra) to the aqueous environment from samples that have been
      treated to represent various stages of leaching and passive closure processes are
      assessed. Dissolution of U from the solid phase has occurred during
      biogeochemical mineral dissolution in the presence of Acidithiobacillus
      ferrooxidans, with gamma spectroscopy indicating an 84% decrease in Uranium-235
      ((235)U) content, a value in accordance with the data obtained by dissolution
      chemistry. Gamma spectroscopy data indicate that only 30% of the (226)Ra was
      removed during the biogeochemical mineral dissolution. Chemical inhibition and
      passivation treatments of waste materials following the biogeochemical mineral
      dissolution offer greater protection against residual U and (226)Ra leaching.
      Pacified samples resist the release of (226)Ra contained in the mineral phase and
      may offer more protection to the aqueous environment for the long term, compared
      to untreated or inhibited residues, and should be taken into account for future
      decommissioning. 

PMID- 24726553
TI  - Early orthopaedic challenges in haemophilia patients and therapeutic approach.
AB  - INTRODUCTION: There is growing evidence that subclinical joint bleeding early in
      life may lead to subtle changes in joint function, gait, and muscle development
      in young children with haemophilia. The early identification of such changes
      provides an opportunity for clinicians to intervene before irreversible
      structural changes occur. MATERIALS AND METHODS: We have undertaken motion
      analysis of the knee in 273 children (mean age 9.8 years) with haemophilia A,
      haemophilia B, or von Willebrand disease and compared the results with those from
      200 healthy age- and sex-matched controls (mean age 10.3 years). We have also
      completed detailed orthopaedic assessments and evaluated overall fitness in most
      of these children. RESULTS: There was a clear correlation between total motion
      score and age: r(2)=0.47 for the healthy children and r(2)=0.69 for the
      haemophilic children. The differences were most striking in children aged 3-4
      years. Significant between-group differences were also observed in the comparison
      of knee bends, gait scores, and rhythmicity. Orthopaedic examinations revealed
      previously clinically silent pressure pains in the ligaments of the knee joints
      of 38% of children and in the ligaments and capsule of the ankle joints of 60% of
      children. The five-item fitness check showed significant deficits relative to
      controls in overall fitness, endurance, coordination, and flexibility.
      CONCLUSIONS: Children and adolescents with haemophilia show significant
      functional impairments relative to normal controls. Early comprehensive
      assessments of the musculoskeletal system should be made so that individualized
      physical, physiotherapy, and sports therapy programmes can be developed.

PMID- 24726554
TI  - Relationship between haemophilia and social status.
AB  - The impact of haemophilia and its treatment on social status has not been well
      studied, although research into the quality of life of patients with haemophilia
      has shed some light on aspects of social and role functioning. Studies conducted
      before the advent of safe and effective coagulation factor replacement therapy
      suggest that the haemophilia population was predominantly of low socioeconomic
      status with many social disadvantages, including high rates of disability and
      unemployment and low rates of marriage. Since the availability of purified factor
      VIII concentrates that could be used in a home-care setting and as prophylaxis,
      most research suggests that social status and well-being amongst children,
      adolescents, and adults with haemophilia is not compromised, and is comparable to
      that of the general population. Children and adolescents with haemophilia do not
      generally feel disadvantaged, although haemophilia-related issues at school and
      amongst peer groups do arise. Recent studies in adults show higher than average
      rates of marriage and cohabitation and the attainment of a generally good
      educational status, but, as in the past, employment rates remain comparatively
      lower. Social status amongst the elderly with haemophilia who may have developed
      severe disability as a result of their condition is poorly defined and has never
      been formally studied. Additional research is recommended. 

PMID- 24726555
TI  - Pathogen safety of Beriate(r).
AB  - Plasma-derived factor VIII (FVIII) concentrates have been used successfully to
      treat haemophilia A since the late 1960s. To ensure the pathogen safety of the
      plasma-derived FVIII concentrate, Beriate((r)) (formerly Beriate((r)) P), donors
      of blood/plasma are carefully selected and all donations are screened for
      hepatitis B virus surface antigen (HBsAg), antibodies against HIV types 1 and 2
      (HIV-1/HIV-2) and hepatitis C virus (HCV), and genomic material of hepatitis A
      virus (HAV), hepatitis B virus (HBV), HCV, and for high titres of parvovirus B19
      (B19V). As additional quality control, plasma pools for fractionation are only
      released for further processing when non-reactivity has been demonstrated in
      serological and genome amplification assays. The manufacturing process for
      Beriate((r)) comprises dedicated virus reduction steps such as pasteurization and
      the recently introduced virus filtration step, resulting in effective
      inactivation of various enveloped and non-enveloped viruses and effective removal
      of viruses and prion material larger than the mean pore size of the virus filter
      (19 nm). The effectiveness of these production steps has been demonstrated in
      virus and prion validation studies using a range of different viruses and prion
      preparations. The multiple precautionary measures inherent to the overall
      production process for Beriate((r)) (and its predecessor Beriate((r)) P) are
      reflected in an excellent safety record documented during 20 years of clinical
      use with no proven record of virus transmission, even before the introduction of
      the virus filtration step. Continued improvement of safety measures according to
      scientific knowledge and regulatory guidance maintains and even enhances the
      excellent safety profile of Beriate((r)).

PMID- 24726556
TI  - Anti-inflammatory effects of diethylcarbamazine: a review.
AB  - Diethylcarbamazine (DEC) interferes with cyclooxygenase and lipoxygenase
      pathways, reducing the production of thromboxane, prostacyclin, prostaglandin and
      leukotrienes. Recent studies using different experimental models of inflammation
      have indicated that DEC, in addition to inhibiting cyclooxygenase and
      lipoxygenase pathways, also inhibits nuclear transcription factor kappa B (NF
      kappaB) activation, which is a key regulator of proinflammatory genes such as TNF
      alpha, IL-1beta, inducible nitric oxide synthase (iNOS) and even cyclooxygenase 2
      (COX-2). The aim of the present study is to provide a comprehensive summary of
      DEC, including a description of filaricidal action, inhibition of synthesis and
      secretory pathways, immunomodulatory activity, and specific inhibition of
      lipoxygenase and cyclooxygenase pathways. 

PMID- 24726557
TI  - Protective effects of gallic acid against chronic cerebral hypoperfusion-induced
      cognitive deficit and brain oxidative damage in rats.
AB  - Free radical-induced neural damage is implicated in cerebral hypoperfusion
      disorders and antioxidants have protective effects. In the present study, we
      examined the effect of gallic acid (GA; 100mg/kg, p.o. for 10 days) on cognitive
      deficit and cerebral oxidative stress induced by permanent bilateral common
      carotid artery occlusion (2VO) as an animal model of vascular dementia (VD). The
      results showed that 2VO significantly reduced the spatial memory performance in
      Morris water maze as well as non-enzymatic (total thiol) and enzymatic
      [glutathione peroxidase (GPx)] antioxidant contents and increased the level of
      malondialdehyde (MDA) in the hippocampus and frontal cortex of vehicle-treated
      group as compared to sham-operated rats. Furthermore, chronic administration of
      GA significantly restored the spatial memory, total thiol and GPx contents and
      also decreased MDA levels in these tissues. GA alone did not show any change
      neither in the status of various antioxidants nor behavioral tests over sham
      values. The results demonstrate that GA has beneficial activity against 2VO
      induced cognitive deficits via enhancement of cerebral antioxidant defense. Taken
      together, the present study suggested that GA might be useful in the treatment of
      VD. 

PMID- 24726558
TI  - Different effects of local anesthetics on extracellular signal-regulated kinase
      phosphorylation in rat dorsal horn neurons.
AB  - Local anesthetics, which are widely known to be neuronal voltage-gated Na(+)
      channel blockers, also affect a variety of other ion channels, N-methyl-d
      asparate (NMDA) receptors and alpha-amino-3-hydroxy-5-methyl-4-izoxazolepropionic
      acid (AMPA) receptors. Glutamate, which is released from presynaptic fibers,
      activates extracellular signal-regulated kinase (ERK) through NMDA and AMPA
      receptors in spinal dorsal horn neurons. ERK plays a key role in central
      sensitization, which contributes to the chronicity of pain. We investigated the
      effects of four representative local anesthetics, lidocaine, tetracaine,
      levobupivacaine, and ropivacaine on ERK phosphorylation induced by capsaicin,
      which releases glutamate from presynaptic neurons, NMDA, AMPA, or ionomycin, a
      calcium ionophore, in dorsal neurons. We observed capsaicin-induced
      phosphorylation of ERK, which was suppressed by lidocaine, tetracaine, or
      ropivacaine, but not by levobupivacaine. NMDA-induced phosphorylation of ERK was
      suppressed by lidocaine, tetracaine, or levobupivacaine, but not by ropivacaine.
      AMPA-induced phosphorylation of ERK was suppressed by lidocaine or tetracaine,
      but not by levobupivacaine or ropivacaine. Finally, ionomycin-induced ERK
      phosphorylation was suppressed by lidocaine, tetracaine, or ropivacaine, but not
      by levobupivacaine. Our results suggest that local anesthetics contribute to the
      prevention of the incidence of persistent postsurgical pain with varying
      intensities and through different mechanisms of action. 

PMID- 24726559
TI  - (S)-amisulpride as a discriminative stimulus in C57BL/6 mice and its comparison
      to the stimulus effects of typical and atypical antipsychotics.
AB  - Amisulpride, a substituted benzamide derivative, exerts atypical antipsychotic
      and antidepressant clinical effects and its (S)-stereoisomer is thought to
      underlie these actions. In the present study, male C57BL/6 mice were trained to
      discriminate (S)-amisulpride (10mg/kg, s.c.) from vehicle in a two-lever drug
      discrimination task for food reward. The (S)-amisulpride stimulus was rapidly
      acquired and was shown to be dose-related, time dependent (effective between 30
      and 120min) and stereoselective: (S)-amisulpride (ED50=1.77mg/kg; 4.2umol/kg) was
      about three times more potent than rac-amisulpride (ED50=4.94mg/kg; 13.4umol/kg)
      and ten times more potent than (R)-amisulpride (ED50=15.84mg/kg; 42.9umol/kg). In
      tests of stimulus generalization, the (S)-amisulpride stimulus generalized
      completely to sulpiride (ED50=12.67mg/kg; 37.1umol/kg), a benzamide analog that
      also is purported to be an atypical antipsychotic, but did not fully generalize
      to the typical antipsychotic drug haloperidol (maximum of 45% drug-lever
      responding) nor to the atypical antipsychotic drugs clozapine (partial
      substitution of 65% drug-lever responding) or aripiprazole (~30% drug-lever
      responding). These results demonstrated that (S)-amisulpride appears to exert a
      unique discriminative stimulus effect that is similar to other benzamides, but
      which differs from other structural classes of antipsychotic drugs. 

PMID- 24726560
TI  - Theories about evolutionary origins of human hepatitis B virus in primates and
      humans.
AB  - INTRODUCTION: The human hepatitis B virus causes acute and chronic hepatitis and
      is considered one of the most serious human health issues by the World Health
      Organization, causing thousands of deaths per year. There are similar viruses
      belonging to the Hepadnaviridae family that infect non-human primates and other
      mammals as well as some birds. The majority of non-human primate virus isolates
      were phylogenetically close to the human hepatitis B virus, but like the human
      genotypes, the origins of these viruses remain controversial. However, there is a
      possibility that human hepatitis B virus originated in primates. Knowing whether
      these viruses might be common to humans and primates is crucial in order to
      reduce the risk to humans. OBJECTIVE: To review the existing knowledge about the
      evolutionary origins of viruses of the Hepadnaviridae family in primates.
      METHODS: This review was done by reading several articles that provide
      information about the Hepadnaviridae virus family in non-human primates and
      humans and the possible origins and evolution of these viruses. RESULTS: The
      evolutionary origin of viruses of the Hepadnaviridae family in primates has been
      dated back to several thousand years; however, recent analyses of genomic fossils
      of avihepadnaviruses integrated into the genomes of several avian species have
      suggested a much older origin of this genus. CONCLUSION: Some hypotheses about
      the evolutionary origins of human hepatitis B virus have been debated since the
      '90s. One theory suggested a New World origin because of the phylogenetic co
      segregation between some New World human hepatitis B virus genotypes F and H and
      woolly monkey human hepatitis B virus in basal sister-relationship to the Old
      World non-human primates and human hepatitis B virus variants. Another theory
      suggests an Old World origin of human hepatitis B virus, and that it would have
      been spread following prehistoric human migrations over 100,000 years ago. A
      third theory suggests a co-speciation of human hepatitis B virus in non-human
      primate hosts because of the proximity between the phylogeny of Old and New World
      non-human primate and their human hepatitis B virus variants. The importance of
      further research, related to the subject in South American wild fauna, is
      paramount and highly relevant for understanding the origin of human hepatitis B
      virus.

PMID- 24726561
TI  - A preliminary study to identify locomotor-cognitive dual tasks that reveal
      persistent executive dysfunction after mild traumatic brain injury.
AB  - OBJECTIVE: To identify different combinations of physical (level, obstacle
      avoidance, stepping down) and cognitive (visual, mental) demands within a
      locomotor navigational context that best discriminates between persons with mild
      traumatic brain injury (MTBI) and control subjects for an eventual clinical tool
      to assess residual executive dysfunction. DESIGN: Group comparison study.
      SETTING: Rehabilitation facility. PARTICIPANTS: Volunteer sample (N=14) of
      persons with MTBI (n=7) (6 women; age, 20+/-1.6 y) and a comparison group (n=7)
      of subjects without neurologic problems (6 women; age, 22.4+/-1.4 y).
      INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Gait speed (m/s) and dual
      task cost calculated as the relative change in gait speed from single (no
      cognitive task) to dual tasks for the same gait condition. RESULTS: There were
      significant interactions between groups and cognitive tasks and between groups
      and cognitive and physical tasks for gait speed. Specifically, the MTBI group
      walked slower than control subjects in the dual-task conditions when stepping
      over an obstacle combined with each cognitive task. When gait speed was measured
      as dual-task costs, group differences were more evident, except for stepping
      down. CONCLUSIONS: These preliminary results suggest that both absolute gait
      speed and calculated dual-task costs during the combination of stepping over an
      obstacle with a simultaneous cognitive task are sensitive to revealing executive
      dysfunction in persons with MTBI. Gait speed can be easily measured in the clinic
      to provide important information to make diagnoses and decide about return to
      play or function. Continued work building on these preliminary results is needed
      toward the development of a clinical tool.

PMID- 24726562
TI  - The drain game: abdominal drains for deep inferior epigastric perforator breast
      reconstruction.
AB  - INTRODUCTION: The deep inferior epigastric perforator (DIEP) flap is often
      preferred for breast reconstruction as it allows for autologous reconstruction
      with less donor site morbidity versus transverse rectus abdominis myocutaneous
      (TRAM) flap reconstruction. Our group has presented and published data for the
      duration of donor site back drain use in latissimus dorsi (LD) flap breast
      reconstruction due to insufficient evidence and a requirement for further
      investigation in the literature; this evidence is still lacking for DIEP
      reconstruction. AIM: To compare inpatient hospital stay, drainage parameters and
      donor-site complications associated with closed suction abdominal drain removal
      by post-operative day (POD) 3 regardless of output (early group), with removal
      after POD 3 where instructions were by drainage volume/24 h+/-output consistency
      (late group), in post-mastectomy DIEP reconstruction donor sites. METHOD: A
      retrospective review of DIEP breast reconstructions, between January 2011 and
      July 2012, was undertaken to facilitate 1 year minimum follow-up per patient.
      RESULTS: Of 78 patients who underwent DIEP breast reconstructions, 74 hospital
      records contained complete documentation. There were 41 patients in the late, and
      33 in the early removal group; both groups were matched for age and number of
      donor site drains (2 per patient). Mean drain removal day (4.32+/-0.10 days vs.
      2.87+/-0.06 days, p<0.0001), total drainage (518.90+/-41.53 mls vs. 283.79+/
      18.06 mls; p<0.0001) and hospital inpatient stay were greater for patients in the
      late versus early group. There were no differences in total complications (21.95%
      (9/41) vs. 12.12% (5/33); p=0.46), seroma (4.88% (2/41) vs. 0% (0/33); p=0.20),
      dehiscence (4.88% (2/41) vs. 9.09% (3/33); p=0.47) or haematoma (7.32% (3/41) vs.
      3.0% (1/33); p=0.42) rates between the late and early groups. DISCUSSION: These
      data suggest significant advantages for patients who have abdominal drains
      removed early by POD 3, without increased post-operative complications including
      seroma rates; these data are in keeping with our LD data. We recommend drain
      removal and patient discharge by POD 3.

PMID- 24726563
TI  - Superficial temporal artery aneurysm: beware of the lump with a thump.

PMID- 24726564
TI  - "Windmill flap": a novel technique of abdominal wall reconstruction.

PMID- 24726565
TI  - Asymmetrical control of fixation durations in scene viewing.
AB  - In two experiments we investigated the control of fixation durations in
      naturalistic scene viewing. Empirical evidence from the scene onset delay
      paradigm and numerical simulations of such data with the CRISP model
      [Psychological Review 117 (2010) 382-405] have suggested that processing related
      difficulties may lead to prolonged fixation durations. Here, we ask whether
      processing related facilitation may lead to comparable decreases to fixation
      durations. Research in visual search and reading have reported only uni
      directional shifts. To address the question of unidirectional (slow down) as
      opposed to bidirectional (slow down and speed up) adjustment of fixation
      durations in the context of scene viewing, we used a saccade-contingent display
      change method to either reduce or increase the luminance of the scene during
      prespecified critical fixations. Degrading the stimulus by shifting luminance
      down resulted in an immediate increase to fixation durations. However, clarifying
      the stimulus by shifting luminance upwards did not result in a comparable
      decrease to fixation durations. These results suggest that the control of
      fixation durations in scene viewing is asymmetric, as has been reported for
      visual search and reading. 

PMID- 24726566
TI  - Addition of an iliac/obturator lymph node dissection does not improve nodal
      recurrence or survival in melanoma.
AB  - BACKGROUND: Controversy exists regarding the value and indications for inguinal
      dissection alone or in combination with an iliac/obturator lymph node dissection
      for melanoma. STUDY DESIGN: We reviewed patients from a multicenter prospective
      clinical trial and a single center who underwent inguinal dissection alone or
      combined with an iliac/obturator dissection for cutaneous melanoma. Analyses were
      stratified and compared by microscopic or macroscopic (palpable or detected by
      imaging) disease. RESULTS: The study was composed of 134 patients with a median
      follow-up of 39 months. Indications for inguinal dissection were microscopic
      disease in 94 (70%) patients and macroscopic nodal disease in 40 (30%) patients.
      An iliac/obturator dissection yielded tumor-positive pelvic nodes in 25% vs 55%
      in the microscopic vs macroscopic groups, respectively (p = 0.10). No risk
      factors for positive pelvic nodes were identified. For both microscopic and
      macroscopic disease, addition of an iliac/obturator dissection to an inguinal
      dissection did not significantly reduce the risk of pelvic nodal recurrence. Five
      year overall survival rates for 4 groups were compared: microscopic disease,
      inguinal dissection alone (72%); microscopic disease, iliac/obturator dissection
      (68%); macroscopic disease, inguinal dissection alone (51%); and macroscopic
      disease, iliac/obturator dissection (44%) (p = 0.0163). On survival analysis,
      addition of an iliac/obturator dissection in either microscopic or macroscopic
      disease did not affect disease-free survival or regional lymph node recurrence
      free survival. CONCLUSIONS: The addition of an iliac/obturator dissection to an
      inguinal dissection for both microscopic and macroscopic nodal disease did not
      significantly affect lymph node recurrence rates, disease-free survival, or
      overall survival.

PMID- 24726567
TI  - BIT: Biosignal Igniter Toolkit.
AB  - The study of biosignals has had a transforming role in multiple aspects of our
      society, which go well beyond the health sciences domains to which they were
      traditionally associated with. While biomedical engineering is a classical
      discipline where the topic is amply covered, today biosignals are a matter of
      interest for students, researchers and hobbyists in areas including computer
      science, informatics, electrical engineering, among others. Regardless of the
      context, the use of biosignals in experimental activities and practical projects
      is heavily bounded by the cost, and limited access to adequate support materials.
      In this paper we present an accessible, albeit versatile toolkit, composed of low
      cost hardware and software, which was created to reinforce the engagement of
      different people in the field of biosignals. The hardware consists of a modular
      wireless biosignal acquisition system that can be used to support classroom
      activities, interface with other devices, or perform rapid prototyping of end
      user applications. The software comprehends a set of programming APIs, a
      biosignal processing toolbox, and a framework for real time data acquisition and
      postprocessing. 

PMID- 24726568
TI  - Severe scoliosis in a patient with severe methylenetetrahydrofolate reductase
      deficiency.
AB  - Severe methylenetetrahydrofolate reductase (MTHFR) deficiency is a rare autosomal
      recessively inherited inborn error of folate metabolism. We report a new patient
      with severe MTHFR deficiency who presented at age 4 months with early onset
      severe scoliosis associated with severe hypotonia. Markedly decreased MTHFR
      enzyme activity (0.3 nmoles CHO/mg protein/h; reference range>9) and compound
      heterozygous mutations (c. 1304T>C; p.Phe435Ser and c.1539dup; p.Glu514Argfs*24)
      in the MTHFR gene confirmed the diagnosis. She was treated with vitamin B12,
      folic acid and betaine supplementation and showed improvements in her
      developmental milestones and hypotonia. To the best of our knowledge, this is the
      first patient with MTHFR deficiency reported with severe early onset scoliosis.
      Despite the late diagnosis and treatment initiation, she showed favorable short
      term neurodevelopmental outcome. This case suggests that homocysteine measurement
      should be included in the investigations of patients with developmental delay,
      hypotonia and scoliosis within first year of life prior to organizing genetic
      investigations.

PMID- 24726569
TI  - Airflow limitations in pregnant women suspected of sleep-disordered breathing.
AB  - BACKGROUND AND AIM: Pregnancy physiology may predispose women to the development
      of airflow limitations during sleep. The goal of this study was to evaluate
      whether pregnant women suspected of sleep-disordered breathing (SDB) are more
      likely to have airflow limitations compared to non-pregnant controls. METHODS: We
      recruited pregnant women referred for polysomnography for a diagnosis of SDB. Non
      pregnant female controls matched for age, body mass index (BMI), and apnoea
      hypopnoea index (AHI) were identified from a database. We examined airflow
      tracings for changes in amplitude and shape. We classified airflow limitation by
      (a) amplitude criteria defined as decreased airflow of > or =10 s without
      desaturation or arousal (FL 10), or decreased airflow of any duration combined
      with either 1-2% desaturation or arousal, (FL 1-2%); and (b) shape criteria
      defined as the presence of flattening or oscillations of the inspiratory flow
      curve. RESULTS: We identified 25 case-control pairs. Mean BMI was 44.0+/-6.9 in
      cases and 44.1+/-7.3 in controls. Using shape criteria, pregnant women had
      significantly more flow-limited breaths throughout total sleep time (32.4+/-35.8
      vs. 9.4+/-17.9, p<0.0001) and in each stage of sleep (p<0.0001) than non-pregnant
      controls. In a subgroup analysis, pregnant women without a diagnosis of
      obstructive sleep apnoea (OSA) who had an AHI <5 had similar findings (p<0.0001).
      There was no difference in airflow limitation by amplitude criteria between
      pregnant women and controls (p=0.22). CONCLUSIONS: Pregnant women suspected of
      OSA have more frequent shape-defined airflow limitations than non-pregnant
      controls, even when they do not meet polysomnographic OSA criteria.

PMID- 24726570
TI  - Contextualised urinary biomarker analysis facilitates diagnosis of paediatric
      obstructive sleep apnoea.
AB  - BACKGROUND: Intrinsic variance of the urine proteome limits the discriminative
      power of proteomic analysis and complicates potential biomarker detection in the
      context of paediatric sleep disorders. METHODS AND RESULTS: Using a rigorous
      workflow for proteomic analysis of urine, we demonstrate that gender and diurnal
      effects constitute two important sources of variability in healthy children. In
      the context of disease, complex pathophysiological perturbations magnify these
      proteomic differences and therefore require contextualised biomarker analysis.
      Indeed, by performing biomarker discovery in a gender- and diurnal-dependent
      manner, we identified ~30-fold more candidate biomarkers of paediatric
      obstructive sleep apnoea (OSA), a highly prevalent condition in children
      characterised by repetitive episodes of intermittent hypoxia and hypercapnia, and
      sleep fragmentation in the context of recurrent upper airway obstructive events
      during sleep. Remarkably, biomarkers were highly specific for gender and sampling
      time as poor overlap (~3%) was observed in the proteins identified in boys and
      girls across morning and bedtime samples. CONCLUSIONS: As no clinical basis to
      explain gender-specific effects in OSA or healthy children is apparent, we
      propose that implementation of contextualised biomarker strategies will be
      applicable to a broad range of human diseases, and may be specifically applicable
      to paediatric OSA.

PMID- 24726571
TI  - Predictors of shorter sleep in early childhood.
AB  - OBJECTIVE: The aim of this study was to identify socio-demographic and home
      environmental predictors of shorter sleep in early childhood, and to examine
      whether effects were mediated by the timing of bedtime or wake time. METHODS:
      Participants were from Gemini, a British birth cohort of twins, and included 1702
      children; one randomly selected from each twin pair. Parents reported night-time
      sleep duration at an average age of 15.8 months (range 14-27 months) using a
      modified version of the Brief Infant Sleep Questionnaire. Multiple logistic
      regression models were used to identify predictors of shorter sleep for this
      study. RESULTS: Using a cut-off of <11 h a night, shorter sleep was reported in
      14.1% of children. Lower maternal education, non-white ethnic background, being
      male, low birth weight, living in a home with >1 older child and watching >1 h of
      TV in the evening were independently associated with shorter sleep. Mediation
      analyses showed that associations between education, ethnicity, evening TV
      viewing and sleep were driven predominantly by later bedtimes, while sex
      differences were driven predominantly by earlier wake times in boys. CONCLUSION:
      In this sample, multiple environmental factors were associated with shorter sleep
      in young children, with several operating predominantly through later bedtime. An
      emphasis on the importance of an early and consistent bedtime could help promote
      healthy sleep and reduce inequalities in child health.

PMID- 24726572
TI  - Sleep-related disturbances among adolescents with cancer: a systematic review.
AB  - The purpose of this systematic review was to examine the evidence for sleep
      related disturbances among adolescents with cancer, particularly the types of
      disturbances reported, using single and mixed paediatric oncology samples.
      METHODS: Electronic searches of Medline, PubMed, and the Cochrane Database of
      Systematic Reviews since inception to September 2013 were conducted to identify
      all relevant studies. Search terms included sleep, a second term including
      adolescent, juvenile, youth, child, or childhood, and a third term including
      cancer, leukaemia, or brain tumour. A total of 41 articles met inclusion criteria
      and were included in the review. Of these, 32 included patients with leukaemia
      and 21 included patients with brain tumours. Sleep-related disturbances included
      difficulty initiating sleep, fragmented sleep, disordered breathing, parasomnias,
      napping, daytime sleepiness/fatigue, and unspecified disturbances. Adolescents
      with cancer experience many problems related to sleep. Given the increase in
      survival rates of the youth diagnosed with leukaemia or brain tumours, symptom
      management is an essential area of research in order to continue improving
      quality of life.

PMID- 24726573
TI  - The problem with value.
AB  - Neural correlates of value have been extensively reported in a diverse set of
      brain regions. However, in many cases it is difficult to determine whether a
      particular neural response pattern corresponds to a value-signal per se as
      opposed to an array of alternative non-value related processes, such as outcome
      identity coding, informational coding, encoding of autonomic and skeletomotor
      consequences, alongside previously described "salience" or "attentional" effects.
      Here, I review a number of experimental manipulations that can be used to test
      for value, and I identify the challenges in ascertaining whether a particular
      neural response is or is not a value signal. Finally, I emphasize that some non
      value related signals may be especially informative as a means of providing
      insight into the nature of the decision-making related computations that are
      being implemented in a particular brain region. 

PMID- 24726575
TI  - Aging and motor inhibition: a converging perspective provided by brain
      stimulation and imaging approaches.
AB  - The ability to inhibit actions, one of the hallmarks of human motor control,
      appears to decline with advancing age. Evidence for a link between changes in
      inhibitory functions and poor motor performance in healthy older adults has
      recently become available with transcranial magnetic stimulation (TMS). Overall,
      these studies indicate that the capacity to modulate intracortical (ICI) and
      interhemispheric (IHI) inhibition is preserved in high-performing older
      individuals. In contrast, older individuals exhibiting motor slowing and a
      declined ability to coordinate movement appear to show a reduced capability to
      modulate GABA-mediated inhibitory processes. As a decline in the integrity of the
      GABA-ergic inhibitory processes may emerge due to age-related loss of white and
      gray matter, a promising direction for future research would be to correlate
      individual differences in structural and/or functional integrity of principal
      brain networks with observed changes in inhibitory processes within cortico
      cortical, interhemispheric, and/or corticospinal pathways. Finally, we underscore
      the possible links between reduced inhibitory functions and age-related changes
      in brain activation patterns. 

PMID- 24726576
TI  - Disability in multiple sclerosis: when synaptic long-term potentiation fails.
AB  - Clinical expression of brain damage varies over time and among individuals. This
      is particularly evident in Multiple Sclerosis (MS) where the expression clinico
      radiological paradox has been coined to indicate the weak association between
      common neuroradiological markers of MS and clinical disability. Here we will
      review available data suggesting a possible role of adaptive synaptic long-term
      potentiation (LTP) in the clinical course of MS. We propose that the capacity of
      the brain to potentiate synaptic excitability in a long-lasting way is the
      brain's core adaptive property to bridge neuronal damage and clinical expression
      in multiple sclerosis. LTP, in fact, consists in the strengthening of synaptic
      communication between two connected neurons, and is virtually able therefore to
      restore membrane excitability of neurons that have lost part of their synaptic
      inputs. Recent studies have shown that cortical LTP reserve, explored through
      transcranial magnetic stimulation (TMS), contrasts disability progression in MS.
      Furthermore, promotion of cortical LTP through TMS induces acute cortical
      remapping and ameliorates motor symptoms in MS and in other neurological
      disorders. 

PMID- 24726574
TI  - Lifelong opioidergic vulnerability through early life separation: a recent
      extension of the false suffocation alarm theory of panic disorder.
AB  - The present paper is the edited version of our presentations at the "First World
      Symposium On Translational Models Of Panic Disorder", in Vitoria, E.S., Brazil,
      on November 16-18, 2012. We also review relevant work that appeared after the
      conference. Suffocation-False Alarm Theory (Klein, 1993) postulates the existence
      of an evolved physiologic suffocation alarm system that monitors information
      about potential suffocation. Panic attacks maladaptively occur when the alarm is
      erroneously triggered. The expanded Suffocation-False Alarm Theory (Preter and
      Klein, 2008) hypothesizes that endogenous opioidergic dysregulation may underlie
      the respiratory pathophysiology and suffocation sensitivity in panic disorder.
      Opioidergic dysregulation increases sensitivity to CO2, separation distress and
      panic attacks. That sudden loss, bereavement and childhood separation anxiety are
      also antecedents of "spontaneous" panic requires an integrative explanation. Our
      work unveiling the lifelong endogenous opioid system impairing effects of
      childhood parental loss (CPL) and parental separation in non-ill, normal adults
      opens a new experimental, investigatory area. 

PMID- 24726577
TI  - Modulation of defensive behavior by Transient Receptor Potential Vanilloid Type-1
      (TRPV1) channels.
AB  - The Transient Receptor Potential Vanilloid Type-1 (TRPV1) was first characterized
      in primary afferent fibers as a receptor for capsaicin (the pungent ingredient of
      chili peppers). Later on, this cation-permeable ion channel was also described in
      the central nervous system, where its main putative endogenous ligand is N
      arachidonoyl ethanolamide (an endocannabinoid, also known as anandamide). Recent
      results employing genetic, pharmacological and histochemical techniques indicate
      that TRPV1 tonically modulate anxiety, fear and panic responses in brain regions
      related to defensive responses, such as the dorsal periaqueductal gray, the
      hippocampus and the medial prefrontal cortex. Genetic deletion or antagonism of
      this ion channel induces anxiolytic-like effects in several animal models. The
      main mechanism responsible for TRPV1-mediated effects on anxiety seems to involve
      facilitation of glutamatergic neurotransmission. In addition, there is evidence
      for interactions with other neurotransmitter systems, such as nitric oxide and
      endocannabinoids. 

PMID- 24726578
TI  - Ultrasonic vocalizations in Shank mouse models for autism spectrum disorders:
      detailed spectrographic analyses and developmental profiles.
AB  - Autism spectrum disorders (ASD) are a class of neurodevelopmental disorders
      characterized by persistent deficits in social behavior and communication across
      multiple contexts, together with repetitive patterns of behavior, interests, or
      activities. The high concordance rate between monozygotic twins supports a strong
      genetic component. Among the most promising candidate genes for ASD is the SHANK
      gene family, including SHANK1, SHANK2 (ProSAP1), and SHANK3 (ProSAP2). SHANK
      genes are therefore important candidates for modeling ASD in mice and various
      genetic models were generated within the last few years. As the diagnostic
      criteria for ASD are purely behaviorally defined, the validity of mouse models
      for ASD strongly depends on their behavioral phenotype. Behavioral phenotyping is
      therefore a key component of the current translational approach and requires
      sensitive behavioral test paradigms with high relevance to each diagnostic
      symptom category. While behavioral phenotyping assays for social deficits and
      repetitive patterns of behavior, interests, or activities are well-established,
      the development of sensitive behavioral test paradigms to assess communication
      deficits in mice is a daunting challenge. Measuring ultrasonic vocalizations
      (USV) appears to be a promising strategy. In the first part of the review, an
      overview on the different types of mouse USV and their communicative functions
      will be provided. The second part is devoted to studies on the emission of USV in
      Shank mouse models for ASD. Evidence for communication deficits was obtained in
      Shank1, Shank2, and Shank3 genetic mouse models for ASD, often paralleled by
      behavioral phenotypes relevant to social deficits seen in ASD. 

PMID- 24726579
TI  - Effect of antipsychotic medication on overall life satisfaction among individuals
      with chronic schizophrenia: findings from the NIMH CATIE study.
AB  - The field of schizophrenia is redefining optimal outcome, moving beyond clinical
      remission to a more comprehensive model including functional recovery and
      improved subjective well-being. Although numerous studies have evaluated
      subjective outcomes within the domain of subjective quality of life in patients
      with schizophrenia, less is known about global evaluations of subjective well
      being. This study examined the effects of antipsychotic medication on overall
      life satisfaction in patients with chronic schizophrenia. Data were drawn from
      the Clinical Antipsychotic Trial of Intervention Effectiveness (CATIE) study,
      where participants with a DSM-IV diagnosis of schizophrenia were randomized to
      receive olanzapine, perphenazine, quetiapine, risperidone or ziprasidone under
      double-blind conditions (N=753). The primary outcome measure was prospective
      change in subjectively evaluated overall life satisfaction scores following 12
      months of antipsychotic treatment. Psychopathology, medication side effects and
      functional status were also evaluated, among other variables. Patients
      experienced modest improvements in overall life satisfaction (d=0.22, p<0.001),
      with no differences between antipsychotic medications (all tests, p>0.05). Change
      in severity of positive, negative, and depressive symptoms as well as functional
      status each demonstrated a small, albeit statistically significant, association
      with change in life satisfaction (r=0.10-0.21, p's<0.01). In a multivariate
      regression model, change in clinical symptoms and functional status had limited
      independent predictive value for change in life satisfaction scores (explained
      variance <3%). These data suggest that despite antipsychotic medications being
      effective for symptom-based psychopathology, such clinical effectiveness does not
      necessarily translate to improved general satisfaction with life. Clinicians
      should be aware that these two domains are not inextricably linked. 

PMID- 24726580
TI  - Connectomics: a new paradigm for understanding brain disease.
AB  - In recent years, pathophysiological models of brain disorders have shifted from
      an emphasis on understanding pathology in specific brain regions to
      characterizing disturbances of interconnected neural systems. This shift has
      paralleled rapid advances in connectomics, a field concerned with comprehensively
      mapping the neural elements and inter-connections that constitute the brain.
      Magnetic resonance imaging (MRI) has played a central role in these efforts, as
      it allows relatively cost-effective in vivo assessment of the macro-scale
      architecture of brain network connectivity. In this paper, we provide a brief
      introduction to some of the basic concepts in the field and review how recent
      developments in imaging connectomics are yielding new insights into brain
      disease, with a particular focus on Alzheimer's disease and schizophrenia.
      Specifically, we consider how research into circuit-level, connectome-wide and
      topological changes is stimulating the development of new aetiopathological
      theories and biomarkers with potential for clinical translation. The findings
      highlight the advantage of conceptualizing brain disease as a result of
      disturbances in an interconnected complex system, rather than discrete pathology
      in isolated sub-sets of brain regions. 

PMID- 24726581
TI  - The effect of prolonged exposure to morphine on canine cerebral 5-HT2A receptors
      measured with (123)I-R91150 SPECT.
AB  - Down-stream neuronal alterations, including changes in the 5-HT-2A receptor
      system, play an important role in the etiology and treatment of depression. The
      present study examined the effect of prolonged opioid treatment on cerebral 5
      HT2A receptors. Cerebral 5-HT2A receptor availability was estimated in seven
      healthy five-year-old female neutered Beagle dogs pre and post 10-day morphine
      treatment (oral sustained release morphine 20mg twice daily for 10 days) with
      (123)I-R-91150, a 5-HT2A selective radioligand, and SPECT. 5-HT2A receptor
      binding indices (BI) for the frontal, parietal, temporal and occipital cortex and
      the subcortical region were calculated. Statistical analysis was performed using
      a linear mixed-effect model with treatment as fixed effect and dog as random
      effect. Morphine treatment significantly (P<=0.05) lowered 5-HT2A BIs in the
      right and left frontal cortex, the right and left temporal cortex, the right and
      left parietal cortex, and the subcortical region. The decreased cerebral 5-HT2A
      receptor availability following prolonged morphine exposure provides further
      evidence for an interaction between the opioid and serotonergic system. 

PMID- 24726582
TI  - Brain imaging in type 2 diabetes.
AB  - Type 2 diabetes mellitus (T2DM) is associated with cognitive dysfunction and
      dementia. Brain imaging may provide important clues about underlying processes.
      This review focuses on the relationship between T2DM and brain abnormalities
      assessed with different imaging techniques: both structural and functional
      magnetic resonance imaging (MRI), including diffusion tensor imaging and magnetic
      resonance spectroscopy, as well as positron emission tomography and single-photon
      emission computed tomography. Compared to people without diabetes, people with
      T2DM show slightly more global brain atrophy, which increases gradually over time
      compared with normal aging. Moreover, vascular lesions are seen more often,
      particularly lacunar infarcts. The association between T2DM and white matter
      hyperintensities and microbleeds is less clear. T2DM has been related to
      diminished cerebral blood flow and cerebrovascular reactivity, particularly in
      more advanced disease. Diffusion tensor imaging is a promising technique with
      respect to subtle white matter involvement. Thus, brain imaging studies show that
      T2DM is associated with both degenerative and vascular brain damage, which
      develops slowly over the course of many years. The challenge for future studies
      will be to further unravel the etiology of brain damage in T2DM, and to identify
      subgroups of patients that will develop distinct progressive brain damage and
      cognitive decline. 

PMID- 24726583
TI  - The dark side of social support: understanding the role of social support,
      drinking behaviors and alcohol outlets for child physical abuse.
AB  - The purpose of this study is to examine how parental drinking behavior, drinking
      locations, alcohol outlet density, and types of social support (tangible,
      emotional, and social companionship) may place children at greater risk for
      physical abuse. Data on use of physical abuse, drinking behaviors, types of
      social support, social networks, and demographic information were collected via
      telephone interviews with 3,023 parent respondents in 50 cities in California.
      Data on alcohol outlet density were obtained by the California Department of
      Alcoholic Beverage Control. Multilevel Poisson models were used to analyze data
      for the drinking levels in the entire sample and dose-response drinking models
      for drinkers. Social companionship support was related to more frequent use of
      physical abuse. Having a higher percentage of social companionship support
      network living within the neighborhood was related to more frequent physical
      abuse in the full sample. This relationship was moderated by on-premise alcohol
      outlet density. With regards to drinking behaviors, drinking behaviors from ex
      drinkers to frequent heavy drinkers used physically abusive parenting practices
      more often than lifetime abstainers. The dose-response models show that each
      additional drinking event at a bar or home/party was related to more frequent use
      of physical abuse. Practitioners working with parents who abuse their children
      should be aware that not all social support is beneficial. Findings build
      evidence that child maltreatment is influenced by the interaction between
      individual and ecological factors. 

PMID- 24726584
TI  - Engaging religious communities to protect children from abuse, neglect, and
      exploitation: partnerships require analysis of religious virtues and harms.

PMID- 24726585
TI  - Diagnosis of mitochondrial neurogastrointestinal encephalomyopathy: proposal of a
      clinical algorithm.

PMID- 24726586
TI  - Hepatic ischemia/reperfusion injury is diminished by atorvastatin in Wistar rats.
AB  - BACKGROUND AND AIMS: Temporal occlusion of the hepatoduodenal ligament (HDL) is
      often used during liver surgeries in order to reduce blood loss, resulting in
      ischemia/reperfusion injury (I/R). The aim of the study was to investigate the
      effects of atorvastatin (ATOR) on hepatic I/R injury and on serum levels of tumor
      necrosis factor-alpha (TNF-alpha), endothelin-1 (ET-1), antithrombin III (ATIII)
      and intracellular adhesion molecule-1 (ICAM-1). METHODS: Liver ischemia was
      induced in Wistar rats by clamping the HDL for 60 min, followed by either 60 or
      180 min reperfusion. Rats received either vehicle or 10 mg/kg ATOR before hepatic
      I/R. Control group received sham surgery. Livers were examined for histological
      damage and serum AST, ALT, TNF-alpha, ET-1, ATIII and ICAM-1 concentrations were
      measured. RESULTS: After I/R, AST and ALT were significantly elevated, ATIII
      levels were significantly depleted, both TNF-alpha and ICAM-1 levels increased
      and ET-1 was significantly elevated (at 180 min). ATOR pretreatment attenuated
      these alterations and diminished histological injury scores. CONCLUSIONS: Our
      results show that ATOR protects the liver from I/R injury.

PMID- 24726587
TI  - Comparison of polymerization shrinkage of pattern resins.
AB  - STATEMENT OF PROBLEM: The dimensional stability, in particular polymerization
      shrinkage, of pattern resins affects the accuracy of implant prosthesis
      fabrication. Recently introduced photopolymerizing pattern resins are easy to
      use, but their shrinkage needs to be determined and compared with traditional
      autopolymerizing pattern resins. PURPOSE: The purpose of the study was to compare
      the polymerization shrinkage of photopolymerizing pattern resins with
      autopolymerizing pattern resins. MATERIAL AND METHODS: Two autopolymerizing
      (DuraLay, GC Pattern resin) and 2 photopolymerizing (Primopattern LC Gel,
      Primopattern LC Paste) pattern resins were tested. The sample size was 10 for
      each group. Polymerization shrinkage was determined by measuring the change in
      area dimensions with image analysis. The percentage of volumetric shrinkage was
      calculated, and the results were statistically analyzed with ANOVA, followed by
      the Student-Newman-Keuls post hoc test (alpha=.05). RESULTS: The volumetric
      shrinkage values (%; mean +/- standard deviation) for Duralay were [corrected]
      5.72 +/- 0.89; for GC pattern resin, [corrected] 5.07 +/- 1.36; for Primopattern
      LC Gel, 5.42 +/- 1.83; and for Primopattern LC Paste, 7.43 +/- 0.62. The
      volumetric shrinkage of the Primopattern LC Paste was significantly higher than
      that of the other 3 materials. CONCLUSIONS: The photopolymerizing pattern resin
      in gel form (Primopattern LC Gel) had a similar shrinkage value to the
      autopolymerizing pattern resins (DuraLay and GC Pattern Resin). However, the
      photopolymerizing pattern resin in paste form (Primopattern LC Paste) shrank
      significantly more than the other 3 materials tested.

PMID- 24726588
TI  - A correlation between bone (B), insertion torque (IT), and implant stability (S):
      BITS score.
AB  - STATEMENT OF PROBLEM: Although criteria for assessing bone quality have been
      reported, an overall score that correlates bone quality with the primary
      stability and secondary stability of implants is not yet available. PURPOSE: The
      purpose of this article was to propose a scoring index that will establish a
      correlation among the bone density values from computed tomography, maximum
      insertion torque values, and resonance frequency analysis in different phases of
      implant treatment. MATERIAL AND METHODS: In this study, 60 implant sites were
      evaluated to assess bone density (Hounsfield units), insertion torque values
      (Ncm), and primary stability and secondary stability (implant stability quotient
      values obtained by using resonance frequency analysis). On the basis of computed
      tomography data, the bone was classified as D1 to D4. The insertion torque was
      noted and classified into 2 groups, A and B. The implant stability quotient
      values obtained from resonance frequency analysis depicting primary stability and
      secondary stability were classified into 5 groups. The primary score noted was a
      result of the values obtained for the 3 parameters at the time of implant
      placement. The secondary score was obtained by considering the values of the bone
      density and resonance frequency analysis recorded at different time intervals.
      RESULTS: Bone densities of D2, D3, and D4 were noted, dividing the bone type into
      3 groups. The maximum torque noted in the study was 40 Ncm. The difference
      between various insertion torque values and bone types was found to be
      statistically nonsignificant. Higher mean implant stability quotient values were
      obtained for primary and secondary stability for the D2 bone than for D3 and D4
      bone. When analyzed according to the time of insertion, the mean values increased
      at second stage surgery in all bone types. The difference in mean values among
      all bone types was found to be statistically significant (P<.001). A comparison
      of primary and secondary implant stability quotient values in all bone types did
      not find any statistical significance (P=.780). A score was recorded at the time
      of implant placement and at the time of second stage surgery, and the prosthetic
      treatment was planned accordingly. CONCLUSIONS: The score highlights the
      importance of considering the association of bone quality, insertion torque
      values, and stability as denoted by implant stability quotient throughout
      treatment. Based on the variation in the score noted at recall visits,
      alterations in the treatment plan can be made with respect to the healing period
      and prosthetic design.

PMID- 24726589
TI  - Effect of restoration volume on stresses in a mandibular molar: a finite element
      study.
AB  - STATEMENT OF PROBLEM: There can be significant disagreement among dentists when
      planning treatment for a tooth with a failing medium-to-large--sized restoration.
      The clinician must determine whether the restoration should be replaced or
      treated with a crown, which covers and protects the remaining weakened tooth
      structure during function. PURPOSE: The purpose of this study was to evaluate the
      stresses generated in different sized amalgam restorations via a computational
      modeling approach and reveal whether a predictable pattern emerges. MATERIAL AND
      METHODS: A computer tomography scan was performed of an extracted mandibular
      first molar, and the resulting images were imported into a medical imaging
      software package for tissue segmentation. The software was used to separate the
      enamel, dentin, and pulp cavity through density thresholding and surface
      rendering. These tissue structures then were imported into 3-dimensional computer
      aided design software in which material properties appropriate to the tissues in
      the model were assigned. A static finite element analysis was conducted to
      investigate the stresses that result from normal occlusal forces. Five models
      were analyzed, 1 with no restoration and 4 with increasingly larger restoration
      volume proportions: a normal-sized tooth, a small-sized restoration, 2 medium
      sized restorations, and 1 large restoration as determined from bitewing
      radiographs and occlusal surface digital photographs. RESULTS: The resulting von
      Mises stresses for dentin-enamel of the loaded portion of the tooth grew
      progressively greater as the size of the restoration increased. The average
      stress in the normal, unrestored tooth was 4.13 MPa, whereas the smallest
      restoration size increased this stress to 5.52 MPa. The largest restoration had a
      dentin-enamel stress of 6.47 MPa. A linear correlation existed between
      restoration size and dentin-enamel stress, with an R(2) of 0.97. CONCLUSIONS: A
      larger restoration volume proportion resulted in higher dentin-enamel stresses
      under static loading. A comparison of the von Mises stresses to the yield
      strengths of the materials revealed a relationship between a tooth's restoration
      volume proportion and the potential for failure, although factors other than
      restoration volume proportion may also impact the stresses generated in moderate
      sized restorations.

PMID- 24726590
TI  - Three-dimensional repositioning accuracy of semiadjustable articulator cast
      mounting systems.
AB  - STATEMENT OF PROBLEM: In spite of its importance in prosthesis precision and
      quality, the 3-dimensional repositioning accuracy of cast mounting systems has
      not been reported in detail. PURPOSE: The purpose of this study was to quantify
      the 3-dimensional repositioning accuracy of 6 selected cast mounting systems.
      Five magnetic mounting systems were compared with a conventional screw-on system.
      MATERIAL AND METHODS: Six systems on 3 semiadjustable articulators were
      evaluated: Denar Mark II with conventional screw-on mounting plates (DENSCR) and
      magnetic mounting system with converter plates (DENCON); Denar Mark 330 with in
      built magnetic mounting system (DENMAG) and disposable mounting plates; and Artex
      CP with blue (ARTBLU), white (ARTWHI), and black (ARTBLA) magnetic mounting
      plates. Test casts with 3 high-precision ceramic ball bearings at the mandibular
      central incisor (Point I) and the right and left second molar (Point R; Point L)
      positions were mounted on 5 mounting plates (n=5) for all 6 systems. Each cast
      was repositioned 10 times by 4 operators in random order. Nine linear (Ix, Iy,
      Iz; Rx, Ry, Rz; Lx, Ly, Lz) and 3 angular (anteroposterior, mediolateral,
      twisting) displacements were measured with a coordinate measuring machine. The
      mean standard deviations of the linear and angular displacements defined
      repositioning accuracy. RESULTS: Anteroposterior linear repositioning accuracy
      ranged from 23.8 +/-3.7 MUm (DENCON) to 4.9 +/-3.2 MUm (DENSCR). Mediolateral
      linear repositioning accuracy ranged from 46.0 +/-8.0 MUm (DENCON) to 3.7 +/-1.5
      MUm (ARTBLU), and vertical linear repositioning accuracy ranged from 7.2 +/-9.6
      MUm (DENMAG) to 1.5 +/-0.9 MUm (ARTBLU). Anteroposterior angular repositioning
      accuracy ranged from 0.0084 +/-0.0080 degrees (DENCON) to 0.0020 +/-0.0006
      degrees (ARTBLU), and mediolateral angular repositioning accuracy ranged from
      0.0120 +/-0.0111 degrees (ARTWHI) to 0.0027 +/-0.0008 degrees (ARTBLU). Twisting
      angular repositioning accuracy ranged from 0.0419 +/-0.0176 degrees (DENCON) to
      0.0042 +/-0.0038 degrees (ARTBLA). One-way ANOVA found significant differences
      (P<.05) among all systems for Iy, Ry, Lx, Ly, and twisting. CONCLUSIONS:
      Generally, vertical linear displacements were less likely to reach the threshold
      of clinical detectability compared with anteroposterior or mediolateral linear
      displacements. The overall repositioning accuracy of DENSCR was comparable with 4
      magnetic mounting systems (DENMAG, ARTBLU, ARTWHI, ARTBLA). DENCON exhibited the
      worst repositioning accuracy for Iy, Ry, Lx, Ly, and twisting.

PMID- 24726591
TI  - A simplified pocket reduction procedure around a stud attachment without
      suturing.
AB  - Plaque accumulation on the implant titanium surface plays a critical role in the
      initiation and progression of periimplant disease. Removing plaque and calculus
      deposits, and reducing the periimplant probing depth, therefore, are important.
      The reduction of the periimplant probing depth in periimplant disease by using a
      cord and a surgical dressing pack has not been previously reported. This
      procedure is useful for periimplant mucositis and mild periimplantitis before a
      surgical intervention and can maintain a narrow keratinized mucosa with less pain
      than surgical intervention. 

PMID- 24726592
TI  - Laypersons' esthetic perception of various computer-generated diastemas: a pilot
      study.
AB  - STATEMENT OF PROBLEM: Managing excess anterior spacing is a common problem in
      dental practice. During orthodontic or restorative treatment planning, clinicians
      must decide how to distribute this space. However, few reports are available in
      the dental literature about the attractiveness and esthetic impact of anterior
      spaces other than midline diastemas. PURPOSE: The purpose of this study was to
      compare the esthetic perception of 4 different anterior diastemas, including
      simian diastemas (symmetrical diastemas between lateral incisor and canine),
      diastemas suggested by Frush and Fisher (asymmetrical diastemas between lateral
      incisor and canine and between central and lateral incisor), and by Lombardi
      (slight midline diastema and 2 larger diastemas between central and lateral
      incisors), and a midline diastema. MATERIAL AND METHODS: A picture of a young
      woman's smiling face was modified by using photoediting software to create the 4
      previously mentioned diastemas. The resulting pictures were presented to
      laypersons questioned in French public places. The participants were asked to
      rank the pictures from most to least attractive, then to rate them with a mark
      from 1 to 10. RESULTS: One hundred and five participants completed the
      questionnaire. The median ranks and scores attributed to the pictures from most
      to least attractive were as follows: simian diastemas, 1 and 8; Frush and Fisher
      diastemas, 2 and 7; Lombardi diastemas, 3 and 5; and midline diastemas, 4 and 4,
      respectively. The hierarchy (simian diastemas>Frush and Fisher diastemas>Lombardi
      diastemas>midline diastemas) could be established statistically for the scores
      (P=.03, P<.001, and P<.001, respectively) but not for the ranks when adjusting on
      subjects' sex and age (P=.11, P=.03, and P=.06, respectively). CONCLUSIONS: The
      results showed an esthetic hierarchy of anterior diastemas. The negative
      perception of anterior diastemas seems to mainly be related to the presence and
      width of a midline diastema. These results can guide clinical decisions for
      patients with excess anterior spacing.

PMID- 24726593
TI  - Biofilm development by blastospores and hyphae of Candida albicans on abraded
      denture acrylic resin surfaces.
AB  - STATEMENT OF PROBLEM: Candida albicans is a known etiologic agent of denture
      stomatitis. Candida hyphae exhibit the ability to respond directionally to
      environmental stimuli. This characteristic is thought to be important in the
      penetration of substrata such as resilient denture liners and host epithelium. It
      has been suggested that hyphal production also enhances adhesion and survival of
      Candida on host and denture surfaces. Surface roughness, in addition, can enhance
      adhesion where stronger interactions occur between cells and surface features of
      similar dimensions. PURPOSE: The purpose of this study was to assess the
      development of hyphal and blastospore biofilms on abraded denture acrylic resin
      specimens and measure the ease of removal of these biofilms. MATERIAL AND
      METHODS: Biofilms were grown for 48 hours on abraded 1-cm2 denture acrylic resin
      specimens from adhered hyphal phase C albicans or from adhered blastospores.
      Subsequently, all specimens were stained with Calcofluor White and examined with
      confocal scanning laser microscopy. Biofilms were removed by vortex mixing in
      sterile phosphate buffered saline solution. Removed cells were filtered (0.2-MUm
      pore size). Filters were dried at 37 degrees C for 24 hours for dry weight
      measurements. Any cells that remained on the acrylic resin specimens were stained
      with 0.03% acridine orange and examined with epifluorescence microscopy. RESULTS:
      Biofilms grown from both cell types contained all morphologic forms of C
      albicans. Although the underlying surface topography did not affect the amount of
      biofilm produced, biofilms grown from hyphal phase Candida were visibly thicker
      and had greater biomass (P<.05). These biofilms were less easily removed from the
      denture acrylic resin, especially in the case of rougher surfaces, evidenced by
      the higher numbers of retained cells (P<=.05). CONCLUSION: The presence of hyphae
      in early Candida biofilms increased biofilm mass and resistance to removal.
      Increased surface roughness enhances retention of hyphae and yeast cells, and,
      therefore, will facilitate plaque regrowth. Therefore, minimization of denture
      abrasion during cleaning is desirable.

PMID- 24726594
TI  - Effect of surface treatments on the bond strength of soft denture lining
      materials to an acrylic resin denture base.
AB  - STATEMENT OF PROBLEM: Adhesive failure between acrylic resin and resilient liner
      material is commonly encountered in clinical practice. PURPOSE: The purpose of
      this study was to evaluate the effect of different surface treatments on the bond
      strength of 2 different resilient lining materials to an acrylic resin denture
      base. MATERIAL AND METHODS: Ninety-six dumbbell-shaped specimens were fabricated
      from heat-polymerized acrylic resin, and 3 mm of the material was cut from the
      thin midsection. The specimens were divided into 6 groups according to their
      surface treatments: no surface treatment (control group), 36% phosphoric acid
      etching (acid group), erbium:yttrium-aluminum-garnet (Er:YAG) laser (laser
      group), airborne-particle abrasion with 50-MUm Al2O3 particles (abrasion group),
      an acid+laser group, and an abrasion+laser group. The specimens in each group
      were divided into 2 subgroups according to the resilient lining material used:
      heat-polymerized silicone based resilient liner (Molloplast B) and
      autopolymerized silicone-based resilient liner (Ufi Gel P). After all of the
      specimens had been polymerized, they were stored in distilled water at 37 degrees
      C for 1 week. A tensile bond strength test was then performed. Data were analyzed
      with a 2-way ANOVA, and the Sidak multiple comparison test was used to identify
      significant differences (alpha=.05). The effects of the surface treatments and
      resilient lining materials on the surface of the denture base resin were examined
      with scanning electron microscopy. RESULTS: The tensile bond strength was
      significantly different between Molloplast B and Ufi Gel P (P<.001). The
      specimens of the acid group had the highest tensile bond strength, whereas those
      of the abrasion group had the lowest tensile bond strength. The scanning electron
      microscopy observations showed that the application of surface treatments
      modified the surface of the denture base resin. CONCLUSIONS: Molloplast B
      exhibited significantly higher bond strength than Ufi Gel P. Altering the surface
      of the acrylic resin denture base with 36% phosphoric acid etching increased bond
      strength.

PMID- 24726595
TI  - Measurement of total occlusal convergence of 3 different tooth preparations in 4
      different planes by dental students.
AB  - STATEMENT OF PROBLEM: Total occlusal convergence of crown preparation is an
      important didactic and clinical concept in dental education. PURPOSE: The purpose
      of this study was to compare the discrepancy between the total occlusal
      convergence of dental students' typodont crown preparations and the ideal range
      (4 to 10 degrees) in 3 different regions of the mouth and in 4 different planes
      of the teeth. MATERIAL AND METHODS: The dental students of the Class of 2012 at
      Harvard School of Dental Medicine were asked to prepare typodont teeth for crowns
      on 3 different teeth, the maxillary left central incisor (ceramic), mandibular
      left first molar (complete metal), and mandibular left first premolar (metal
      ceramic), during their third year preclinical summative examination and the
      Comprehensive Clinical Examination in their fourth year. Eighteen students
      prepared 3 teeth in their third and fourth years, whereas 19 students
      participated only in their fourth year, for a total of 55 sets of 3 teeth. By
      using custom fit die bases to reproduce the position, a novel procedure of
      measuring each tooth was accomplished in 4 different planes: the faciolingual,
      mesiodistal, mesiofacial-distolingual, and mesiolingual-distofacial. The total
      occlusal convergence of each image was measured with a computer screen
      protractor. The gingival 2 mm of the axial wall was used to determine the taper
      of each wall. Linear mixed model analysis was used to estimate and compare the
      total occlusal convergences of different teeth and planes (alpha=.05). Bonferroni
      corrections were used to adjust for post hoc multiple comparisons. RESULTS: The
      mean total occlusal convergence varied by tooth and plane (2-way interaction;
      P<.001). For the first molar, dental students excessively tapered in all 4
      planes; the model-predicted 99% CIs for the total occlusal convergence were as
      follows: faciolingual (12.7, 19.4), mesiodistal (14.0, 19.3), mesiofacial
      distolingual (13,4, 19.4), and mesiolingual-distofacial (13.7, 19.1). For the
      central incisor, 99% CIs for the total occlusal convergence were (15.9, 24.4) for
      the faciolingual measurement, providing strong evidence of excessive tapering,
      and (4.1, 8.0) for the mesiodistal measurement, which was within the ideal total
      occlusal convergence range. The mesiofacial-distolingual and mesiolingual
      distofacial planes in the central incisor and all 4 planes in the first premolar
      had mean total occlusal convergences that exceeded 10 degrees; however, excessive
      tapering could not be statistically established, because their CIs included
      values within the ideal range. CONCLUSIONS: The present study found significant
      evidence of excessive tapering in a study comparing the total occlusal
      convergence values of crown preparations with those of the ideal preparation for
      3 different teeth in 4 different planes. The total occlusal convergence for the
      molar preparations had the highest mean values.

PMID- 24726596
TI  - Influence of oscillating and rotary cutting instruments with electric and turbine
      handpieces on tooth preparation surfaces.
AB  - STATEMENT OF THE PROBLEM: Rotary and nonrotary cutting instruments are used to
      produce specific characteristics on the axial and marginal surfaces of teeth
      being prepared for fixed restorations. Oscillating instruments have been
      suggested for tooth preparation, but no comparative surface roughness data are
      available. PURPOSE: To compare the surface roughness of simulated tooth
      preparations produced by oscillating instruments versus rotary cutting
      instruments with turbine and electric handpieces. MATERIAL AND METHODS: Different
      grit rotary cutting instruments were used to prepare Macor specimens (n=36) with
      2 handpieces. The surface roughness obtained with rotary cutting instruments was
      compared with that produced by oscillating cutting instruments. The instruments
      used were as follows: coarse, then fine-grit rotary cutting instruments with a
      turbine (group CFT) or an electric handpiece (group CFE); coarse, then medium
      grit rotary cutting instruments with a turbine (group CMT) or an electric
      handpiece (group CME); coarse-grit rotary cutting instruments with a turbine
      handpiece and oscillating instruments at a low-power (group CSL) or high-power
      setting (group CSH). A custom testing apparatus was used to test all instruments.
      The average roughness was measured for each specimen with a 3-dimensional optical
      surface profiler and compared with 1-way ANOVA and the Tukey honestly significant
      difference post hoc test for multiple comparisons (alpha=.05). RESULTS:
      Oscillating cutting instruments produced surface roughness values similar to
      those produced by similar grit rotary cutting instruments with a turbine
      handpiece. The electric handpiece produced smoother surfaces than the turbine
      regardless of rotary cutting instrument grit. CONCLUSION: Rotary cutting
      instruments with electric handpieces produced the smoothest surface, whereas the
      same instruments used with a turbine and oscillating instruments achieved similar
      surface roughness.

PMID- 24726597
TI  - Impact of Blalock-Taussig shunt size on tricuspid regurgitation in hypoplastic
      left heart syndrome.
AB  - BACKGROUND: The prognosis for hypoplastic left heart syndrome (HLHS) has greatly
      improved over the past years, but there is still a significant risk of interstage
      mortality. Tricuspid valve regurgitation (TR) is known to be a risk factor for
      interstage mortality. We hypothesized that a modified Blalock-Taussig (BT) shunt
      with a smaller diameter would lead to a reduction in ventricular volume loading
      with a consequent reduction in TR. METHODS: A retrospective review of all
      patients with HLHS who had a Norwood procedure in our institution between 2006
      and 2011 was performed. Patient demographic, echocardiographic, cardiac magnetic
      resonance imaging, and operative data were reviewed. The impact of BT shunt
      diameter on severity of TR at the time of bidirectional cavopulmonary connection
      (BCPC) was analyzed. RESULTS: Sixty-four neonates with HLHS underwent a Norwood
      procedure with a BT shunt. Thirty-two had a 3.5-mm BT shunt (3.5-mm group), and
      32 had a 3.0-mm BT shunt (3.0-mm group). Survival to BCPC was 53 of 64 patients
      (83%) overall, with 25 of 32 patients (78%) in the 3.5-mm group and 28 of 32
      (88%) in the 3.0-mm group (p = 0.51). The prevalence of significant TR (moderate
      or higher) before BCPC was 9 of 25 patients (36%) in the 3.5-mm group and 2 of 28
      patients (7%) in the 3.0-mm group (odds ratio = 7.3; 95% confidence interval: 1.4
      38; p = 0.018). Tricuspid valve repair was performed in 4 of 25 patients (16%) in
      the 3.5-mm group and 2 of 28 patients (7%) in the 3.0-mm group (p = 0.21).
      CONCLUSIONS: A smaller-diameter BT shunt reduces the prevalence of significant TR
      at the time of BCPC. Further investigation and long-term follow-up are required
      to determine potential complications of this surgical strategy.

PMID- 24726598
TI  - Extrapleural pneumonectomy for malignant mesothelioma: an Italian multicenter
      retrospective study.
AB  - BACKGROUND: This study assessed perioperative outcome and long-term survival in a
      large series of patients with malignant pleural mesothelioma who underwent
      extrapleural pneumonectomy (EPP) to identify prognostic factors allowing better
      patient selection. METHODS: We retrospectively collected data from nine referral
      centers for thoracic surgery in Italy. Perioperative outcome and survival data
      were available for 518 malignant pleural mesothelioma patients (84.4% with
      epithelial tumors, 68.0% with pathologic stage 3 disease) who underwent EPP with
      intention-to-treat (R0/R1) between 2000 and 2010. Induction chemotherapy was
      administered in 271 patients (52.3%) and adjuvant therapy in 373 patients
      (72.0%), including radiotherapy in 213 patients (41.1%), adjuvant chemotherapy in
      43 patients (8.3%), and both in 117 patients (22.6%). RESULTS: In all, 136
      patients (26.3%) had major complications after EPP, and 36 (6.9%) died within 90
      days after surgery. The median overall survival was 18 months, with a 1-, 2-, and
      3-year overall survival of 65%, 41%, and 27%, respectively. At multivariable
      analysis adjusted for age and disease stage, male sex (hazard ratio [HR] 1.47,
      95% confidence interval [CI]: 1.12 to 1.92), nonepithelial histology (HR 1.96,
      95% CI: 1.48 to 2.58), and trimodality treatment using induction chemotherapy (HR
      0.61, 95% CI: 0.43 to 0.85) were significantly associated with survival.
      Development of a major complication also significantly worsened outcome (HR 1.85,
      95% CI: 1.37 to 2.50). CONCLUSIONS: The success of EPP in the context of a
      multimodality treatment depends on a series of patient characteristics. Female
      patients, patients with epithelial tumors, and patients who received induction
      chemotherapy will best benefit from EPP.

PMID- 24726600
TI  - Initial multicenter community robotic lobectomy experience: comparisons to a
      national database.
AB  - BACKGROUND: In pulmonary lobectomy, video-assisted thoracoscopic surgery (VATS)
      offers advantages compared with open thoracotomy. However, various issues have
      limited its adoption, especially in community settings. Single surgeon studies
      suggest that completely portal robotic lobectomy (CPRL) may address such
      limitations. This multicenter study evaluates early CPRL experience in 6
      community cardiothoracic surgeons' practices. METHODS: Perioperative data from
      each surgeon's initial 20, consecutive and unselected cases of CPRL were
      retrospectively gathered (total n = 120) and compared with the 2009 and 2010
      Society of Thoracic Surgeons database for VATS (n = 4,612) and open (n = 5,913)
      lobectomy. The chi(2) and t test procedures were used and significance was
      defined at the 95% confidence level (p < 0.05). RESULTS: One hundred sixteen
      lobectomies (96.7%) were completed robotically with a conversion rate of 3.3%.
      Preoperative patient characteristics were comparable across the CPRL, VATS, and
      open groups. The CPRL was equivalent to VATS on all intraoperative and
      postoperative outcomes, and resulted in significantly lower postoperative blood
      transfusion rates (0.9% vs 7.8%; p = 0.002), air leaks greater than 5 days (5.2%
      vs 10.8%; p = 0.05), chest tube duration (3.2 days vs 4.8 days; p < 0.001), and
      length of stay (4.7 days vs 7.3 days; p < 0.001) when compared with open. For
      these outcomes, results trended favorably for CPRL over VATS. CONCLUSIONS: This
      early CPRL experience reveals a minimally invasive lobectomy technique that is
      safe and reproducible in varied practice settings. Outcomes were equivalent
      between CPRL and VATS, trending in favor of robotics. The CPRL was superior in
      several measures compared with open. The absence of patient selection and low
      conversion rates suggest a broad applicability of this technique.

PMID- 24726599
TI  - Detailed analysis of prognostic factors in primary esophageal small cell
      carcinoma.
AB  - BACKGROUND: Primary small cell carcinoma of the esophagus (SCCE) is characterized
      as highly aggressive with a poor prognosis. To identify potential prognostic
      factors and to assess the role of surgical procedures, chemotherapy, and
      radiotherapy for SCCE, we retrospectively analyzed patients with SCCE from three
      large institutions in China. METHODS: All of the SCCE patients between 1998 and
      2012 were identified from three clinical databases of the Sun Yat-Sen University
      Cancer Center, Peking Union Cancer Hospital and Shantou Cancer Hospital.
      Potential prognostic factors were analyzed with univariate analysis and a Cox
      regression model. Subgroup analysis based on the 2002 American Joint Committee on
      Cancer staging system for esophageal cancer was applied to examine the effect of
      treatment on survival. RESULTS: In patients with stage I/II SCCE, 85% underwent
      operations and showed improved survival (median survival time [MST] 29 vs 17.4
      months, p = 0.082). However, chemotherapy did not further improve survival. In
      patients with stage IIB/III SCCE, chemotherapy, instead of operation, improved
      survival (MST 13.0 vs 6.1 months, p = 0.003), and radiotherapy resulted in
      improved survival. In stage IV patients, chemotherapy improved survival (MST 12.5
      vs 4.0 months, p < 0.001), and chemotherapy combined with radiotherapy was
      superior to chemotherapy alone (MST 13.2 vs 8.9 months, p = 0.014). CONCLUSIONS:
      Surgical procedures alone can be recommended for stage I/IIA patients. In
      patients with stage IIB disease or above, chemotherapy should be the main
      treatment approach, and chemotherapy combined with radiotherapy tended to improve
      survival.

PMID- 24726601
TI  - A propensity-matched comparison of pleurodesis or tunneled pleural catheter for
      heart failure patients with recurrent pleural effusion.
AB  - BACKGROUND: Patients with severe heart failure often have recurrent pleural
      effusions that produce dyspnea and shortness of breath. It is unclear whether
      chemical pleurodesis or the placement of a tunneled pleural catheter that can be
      used for intermittent pleural drainage produces superior palliation, a shorter
      hospital stay, and less morbidity. This investigation compares these two
      treatments. METHODS: Patients with a recurrent, symptomatic, pleural effusion
      secondary to advanced heart failure who had undergone at least two unilateral
      thoracenteses were identified. Two patient groups were formed by propensity
      matching patients who received either talc pleurodesis or a tunneled pleural
      catheter. Patient demographics, length of stay, need for further intervention for
      the pleural effusion, and procedural morbidity and mortality were collected and
      compared. Patients who had undergone ventricular assist device placement or
      cardiac transplant were excluded. RESULTS: Over a 5-year period, 80 patients
      undergoing treatment were identified and propensity matched. All 80 patients were
      classified as having class III or IV heart failure. No significant differences in
      palliation from their effusion were identified. However, the group treated with a
      tunneled pleural catheter realized a significantly shorter hospital stay as well
      as a lower rate of operative morbidity and readmissions than patients undergoing
      talc pleurodesis. CONCLUSIONS: This investigation found that a tunneled pleural
      catheter provided palliation of patients' pleural effusions and freedom from
      reintervention equal to that of talc pleurodesis using thoracoscopy while
      resulting in a shorter mean length of hospital stay. Lower rates of operative
      morbidity and readmission related to the pleural effusion were also seen in the
      tunneled catheter treatment group. This method of palliation of recurrent pleural
      effusion should be considered for symptomatic patients with advanced heart
      failure.

PMID- 24726602
TI  - The impact of acute renal failure on early and late outcomes after thoracic
      aortic endovascular repair.
AB  - BACKGROUND: The incidence of acute kidney injury (AKI) after thoracic aortic
      endovascular repair (TEVAR) is variably reported at 1% to 34%. This study
      utilized the RIFLE (risk, injury, failure) criteria to evaluate the incidence,
      risk factors, and late implications of AKI after TEVAR. METHODS: In all, 350
      patients without prior dialysis requirement underwent TEVAR (1993 to 2013). The
      mean age was 68.7 years (54% male). The mean preoperative glomerular filtration
      rate was 76.5 +/- 37.6 mL/min, with 39 patients (11.7%) in chronic kidney stage 3
      or 4. The TEVAR was performed for rupture in 20.6%. The mean contrast volume
      administered was 95.7 +/- 52.9 mL. RESULTS: Early mortality was seen in 17
      patients (4.9%). Acute kidney injury defined as RIFLE classes risk, injury, or
      failure was seen in 59 patients (17%; risk = 36, injury = 14, failure = 9).
      Independent predictors of AKI included history of saccular aneurysm, presentation
      with rupture, or need for arch repair or red blood cell transfusion (all p <
      0.05). Only 2 patients (0.6%) needed dialysis, with none requiring permanent
      dialysis. Importantly, 10-year freedom from dialysis was 97.7%. Development of
      AKI predicted early mortality (p < 0.001, odds ratio 9.8). Ten-year survival was
      38.1%. Both injury and failure AKI classes independently predicted late mortality
      (p < 0.05). CONCLUSIONS: The prevalence of AKI after TEVAR as assessed by RIFLE
      criteria is higher than seen in previous reports. Despite its infrequent
      progression to permanent dialysis dependence, AKI remains an important risk
      factor for both early and late mortality. Future studies should evaluate
      strategies to reduce the incidence of AKI after TEVAR to improve both early and
      late outcomes.

PMID- 24726603
TI  - The prevalence of nodal upstaging during robotic lung resection in early stage
      non-small cell lung cancer.
AB  - BACKGROUND: Pathologic nodal upstaging can be considered a surrogate for
      completeness of nodal evaluation and quality of surgery. We sought to determine
      the rate of nodal upstaging and disease-free and overall survival with a robotic
      approach in clinical stage I NSCLC. METHODS: We retrospectively reviewed patients
      with clinical stage I NSCLC after robotic lobectomy or segmentectomy at three
      centers from 2009 to 2012. Data were collected primarily based on Society of
      Thoracic Surgeons database elements. RESULTS: Robotic anatomic lung resection was
      performed in 302 patients. The majority were right sided (192; 63.6%) and of the
      upper lobe (192; 63.6%). Most were clinical stage IA (237; 78.5%). Pathologic
      nodal upstaging occurred in 33 patients (10.9% [pN1 20, 6.6%; pN2 13, 4.3%]).
      Hilar (pN1) upstaging occurred in 3.5%, 8.6%, and 10.8%, respectively, for cT1a,
      cT1b, and cT2a tumors. Comparatively, historic hilar upstage rates of video
      assisted thoracoscopic surgery (VATS) versus thoracotomy for cT1a, cT1b, and cT2a
      were 5.2%, 7.1%, and 5.7%, versus 7.4%, 8.8%, and 11.5%, respectively. Median
      follow-up was 12.3 months (range, 0 to 49). Forty patients (13.2%) had disease
      recurrence (local 11, 3.6%; regional 7, 2.3%; distant 22, 7.3%). The 2-year
      overall survival was 87.6%, and the disease-free survival was 70.2%. CONCLUSIONS:
      The rate of nodal upstaging for robotic resection appears to be superior to VATS
      and similar to thoracotomy data when analyzed by clinical T stage. Both disease
      free and overall survival were comparable to recent VATS and thoracotomy data. A
      larger series of matched open, VATS and robotic approaches is necessary.

PMID- 24726604
TI  - Neurodevelopmental outcomes after infant cardiac surgery with circulatory arrest
      and intermittent perfusion.
AB  - BACKGROUND: Optimal perfusion strategies for neuroprotection during infant
      cardiac surgery remain undefined. Despite encouraging experimental data,
      neurodevelopmental (ND) outcomes after cardiac surgery in neonates and infants
      using deep hypothermic circulatory arrest (DHCA) with a period of intermittent
      perfusion have not been reported, and it is not known whether DHCA can be
      extended while preserving ND outcomes. METHODS: Cross-sectional ND evaluation
      with the Bayley Scales of Infant and Toddler Development, Third Edition was
      conducted at 24 months of age. Retrospective clinical data were extracted from
      the electronic medical record. RESULTS: Forty patients underwent cardiac surgery
      during the first year of life using a period of uninterrupted DHCA (24 patients)
      or DHCA interrupted by a period of intermittent perfusion (16 patients). Total
      duration of DHCA ranged from 5 to 74 minutes and did not predict ND scores.
      Despite a longer exposure to DHCA in the intermittent perfusion group (55 minutes
      [1,3 interquartile [IQ] 45.3 to 65.5] versus 38 minutes [1,3 IQ 32 to 40.8]), no
      differences in ND scores were detected. Significant comorbidities, duration of
      intensive care unit and hospital stay, as well as multiple procedures with DHCA
      were independent predictors of ND outcomes at 24 months of age. CONCLUSIONS:
      Despite extended duration of total DHCA, the use of a period of intermittent
      perfusion to limit uninterrupted DHCA periods to less than 45 minutes could lead
      to ND outcomes similar to those of patients exposed to brief periods of DHCA.
      Deep hypothermic circulatory arrest with intermittent perfusion may facilitate
      implementation of prospective studies to identify the optimal cerebral perfusion
      strategy.

PMID- 24726605
TI  - Incidence of postoperative stroke using the Heartstring device in 1,380 coronary
      artery bypass graft patients with mild to severe atherosclerosis of the ascending
      aorta.
AB  - BACKGROUND: Atherosclerotic disease of the ascending aorta during coronary artery
      bypass graft surgery (CABG) increases the risk for postoperative stroke. The
      objective of this study was to examine the incidence of postoperative stroke in
      CABG utilizing the Heartstring (Maquet Cardiovascular, San Jose, CA) proximal
      anastomotic device. METHODS: Intraoperative epiaortic ultrasonography was used to
      grade atherosclerosis in CABG patients at Emory University from April 2003 to
      December 2012. The Heartstring device was utilized in 1,380 patients: 407 (29.5%)
      grade I (minimal atherosclerosis), 367 (26.6%) grade II, 437 (31.7%) grade III,
      110 (8.0%) grade IV, and 59 (4.3%) grade V (severe atherosclerosis). Logistic
      regression analysis was used to estimate the effect of aortic grade on outcomes
      adjusted for Society of Thoracic Surgeons predicted risk of mortality and
      predicted risk of stroke scores. RESULTS: The mean age of all patients was 66.7
      +/- 10.5 years, and 31.9% were female. An increasing risk profile was apparent
      with rising aortic grade. Most CABG was done off pump (n = 1,277, 92.5%). There
      was no significant association between aortic grade and frequency of
      postoperative stroke (p = 0.83). In all patients, use of the Heartstring device
      reduced the predicted risk of stroke by 44% (O:E risk 0.56). The benefit for
      postoperative stroke was least apparent in the grade I aorta patients (O:E 0.8)
      compared with patients having grade II and greater. There were no strokes among
      patients with severe atherosclerosis using the Heartstring device. CONCLUSIONS:
      Compared with the Society of Thoracic Surgeons predicted risk for stroke, the
      Heartstring proximal anastomotic device can be safely used with all aortic
      grades. The most prominent benefit appears to be for patients with grade II
      disease and greater.

PMID- 24726606
TI  - Assessing the energetic costs and trade-offs of a PHA-induced inflammation in the
      subterranean rodent Ctenomys talarum: immune response in growing tuco-tucos.
AB  - A traditional approach used to assess whether immune defense is costly is to
      explore the existence of trade-offs between immunity and other functions;
      however, quantitative studies of the energetic costs associated with the
      activation of the immune system are scarce. We assessed the magnitude of a PHA
      triggered immune response and the associated energetic costs in 60-day old
      Ctenomys talarum. We expected that the magnitude of the macroscopic inflammatory
      response to PHA is lower in young tuco-tucos compared with that of adults, given
      the allocation of substantial energy to growth, and that the magnitude of the
      inflammation is lower in male pups compared to females, due to the higher
      investment in growth of the larger sex. Concomitantly, we expected that the pups
      challenged with PHA show an increase in oxygen consumption compared to control
      animals and that a positive association exists between magnitude of the PHA
      induced inflammation and oxygen consumption. Contrary to what was expected, young
      tuco-tucos mounted a higher inflammatory response compared with adults and there
      were no differences in the magnitude of this response between sexes. The
      inflammatory response induced by a PHA injection did not represent a significant
      energetic cost for young tuco-tucos. There were no differences in oxygen
      consumption between PHA-injected and control animals, and tuco-tucos that mounted
      a higher inflammatory response to PHA did not show higher oxygen consumption.
      Energy expenditure, however, is not the only physiological cost involved in trade
      offs between immune response and various functions of the organism, and other
      currencies are discussed. 

PMID- 24726607
TI  - Adenosinergic regulation of the cardiovascular system in the red-eared slider
      Trachemys scripta.
AB  - Few studies have investigated adenosinergic regulation of the cardiovascular
      system in reptiles. The haemodynamic effect of a bolus intra-arterial adenosine
      injection (2.5 MUM kg-1) was investigated in nine anaesthetised red-eared sliders
      (Trachemys scripta). Adenosine caused a transient bradycardia, which was
      accompanied by systemic vasodilatation as evidenced by an increase in systemic
      flow and a decrease in systemic pressure. Meanwhile, pulmonary flow fell
      significantly. Both the bradycardia and increase in systemic conductance were
      significantly attenuated by theophylline (4 mg kg-1), demonstrating an
      involvement of P1 receptors. These results suggest that adenosine is likely to
      play a significant role in reptile cardiovascular physiology. In turtles
      specifically, adenosinergic regulation may be particularly relevant during
      periods of apnoea.

PMID- 24726608
TI  - Determinants of institutional childbirth service utilisation among women of
      childbearing age in urban and rural areas of Tsegedie district, Ethiopia.
AB  - BACKGROUND: despite receiving greater attention, optimal maternal health remains
      a challenge in developing countries such as Ethiopia. Evidence from various
      studies shows that skilled attendance during childbirth is among the key
      strategies to reduce maternal mortality. However, in Ethiopia, the use of
      institutional childbirth services is very low. In Ethiopia, studies dealing with
      factors affecting women's use of institutional childbirth services are scarce and
      generally focus on urban settings. As such, this study aimed to explore the
      determinants of institutional childbirth service utilisation among urban and
      rural women who gave birth in the previous two years in Tsegedie district,
      Ethiopia. METHODS: a community-based cross-sectional study was performed from 20
      November 2012 to 30 June 2013 on 485 mothers. The participants were selected
      systematically using a multistage sampling technique. A pre-tested structured
      questionnaire, administered by an interviewer, was used to collect quantitative
      data. Focus group discussions and in-depth interviews were used to triangulate
      the evidence from the quantitative study. Bivariate and multivariate data
      analysis was performed using Statistical Package for the Social Sciences Version
      17.0. FINDING: this study found that 31.5% of the respondents used institutional
      childbirth services. The main reason for home birth was close attention from
      family (47%). Women's educational status [adjusted odds ratio (AOR) 5.3, 95%
      confidence interval (CI) 1.59-17.87], time taken to reach the nearest health
      facility (AOR 3.3, 95% CI 1.15-9.52), ultimate decision maker regarding the place
      of childbirth (AOR 3.7, 95% CI 1.08-12.63) and receipt of maternal and child
      health care information (AOR 9.4, 95% CI 2.4-36.38) were significantly associated
      with the use of institutional childbirth services. CONCLUSION: the proportion of
      births attended in health facilities was low in the study district. Women's
      educational status, distance to the nearest health facility, women's decision
      making power and receipt of maternal and child health care information were
      important predictors of institutional childbirth service utilisation. This
      implies that women still lack physical and effective access to maternal health
      care services. Thus, improving community awareness about skilled providers and
      institutional childbirth, targeting women who prefer to give birth at home, is
      encouraged. Safe motherhood education using communication networks in rural and
      urban communities is crucial. Furthermore, it is recommended that essential
      obstetric care facilities (health centres) should be established within a
      reasonable distance of homes, women should be empowered and community midwives
      should be deployed.

PMID- 24726609
TI  - Heterologous overexpression of a monotopic glucosyltransferase (MGS) induces
      fatty acid remodeling in Escherichia coli membranes.
AB  - The membrane protein monoglucosyldiacylglycerol synthase (MGS) from Acholeplasma
      laidlawii is responsible for the creation of intracellular membranes when
      overexpressed in Escherichia coli (E. coli). The present study investigates time
      dependent changes in composition and properties of E. coli membranes during 22h
      of MGS induction. The lipid/protein ratio increased by 38% in MGS-expressing
      cells compared to control cells. Time-dependent screening of lipids during this
      period indicated differences in fatty acid modeling. (1) Unsaturation levels
      remained constant for MGS cells (~62%) but significantly decreased in control
      cells (from 61% to 36%). (2) Cyclopropanated fatty acid content was lower in MGS
      producing cells while control cells had an increased cyclopropanation activity.
      Among all lipids, phosphatidylethanolamine (PE) was detected to be the most
      affected species in terms of cyclopropanation. Higher levels of unsaturation,
      lowered cyclopropanation levels and decreased transcription of the gene for
      cyclopropane fatty acid synthase (CFA) all indicate the tendency of the MGS
      protein to force E. coli membranes to alter its usual fatty acid composition.

PMID- 24726610
TI  - Isolation of a hemidesmosome-rich fraction from a human squamous cell carcinoma
      cell line.
AB  - Hemidesmosomes are cell-to-matrix adhesion complexes anchoring keratinocytes to
      basement membranes. For the first time, we present a method to prepare a fraction
      from human cultured cells that are highly enriched in hemidesmosomal proteins.
      Using DJM-1 cells derived from human squamous cell carcinoma, accumulation of
      hemidesmosomes was observed when these cells were cultured for more than 10 days
      in a commercial serum-free medium without supplemental calcium. Electron
      microscopy demonstrated that numerous electron-dense adhesion structures were
      present along the basal cell membranes of DJM-1 cells cultured under the
      aforementioned conditions. After removing cellular materials using an ammonia
      solution, hemidesmosomal proteins and deposited extracellular matrix were
      collected and separated by electrophoresis. There were eight major polypeptides,
      which were determined to be plectin, BP230, BP180, integrin alpha6 and beta4
      subunits, and laminin-332 by immunoblotting and mass spectrometry. Therefore, we
      designated this preparation as a hemidesmosome-rich fraction. This fraction
      contained laminin-332 exclusively in its unprocessed form, which may account for
      the promotion of laminin deposition, and minimal amounts of Lutheran blood group
      protein, a nonhemidesmosomal transmembrane protein. This hemidesmosome-rich
      fraction would be useful not only for biological research on hemidesmosomes but
      also for developing a serum test for patients with blistering skin diseases. 

PMID- 24726611
TI  - Trunk response to sudden forward perturbations - effects of preload and sudden
      load magnitudes, posture and abdominal antagonistic activation.
AB  - Unexpected loading of the spine is a risk factor for low back pain. The trunk
      neuromuscular and kinematics responses are likely influenced by the perturbation
      itself as well as initial trunk conditions. The effect of four parameters
      (preload, sudden load, initial trunk flexed posture, initial abdominal
      antagonistic activity) on trunk kinematics and back muscles reflex response were
      evaluated. Twelve asymptomatic subjects participated in sudden forward
      perturbation tests under six distinct conditions. Preload did not change the
      reflexive response of back muscles and the trunk displacement; while peak trunk
      velocity and acceleration as well as the relative load peak decreased. Sudden
      load increased reflex response of muscles, trunk kinematics and loading
      variables. When the trunk was initially flexed, back muscles latency was delayed,
      trunk velocity and acceleration increased; however, reflex amplitude and relative
      trunk displacement remained unchanged. Abdominal antagonistic preactivation
      increased reflexive response of muscles but kinematics variables were not
      affected. Preload, initial flexed posture and abdominal muscles preactivation
      increased back muscles preactivity. Both velocity and acceleration peaks of the
      trunk movement decreased with preload despite greater total load. In contrast,
      they increased in the initial flexed posture and to some extent when abdominal
      muscles were preactivated demonstrating the distinct effects of pre-perturbation
      variables on trunk kinematics and risk of injury. 

PMID- 24726612
TI  - [Resistant hypertension and chronic kidney disease: epidemiology and prognosis].
AB  - The emergence of new effective therapeutic strategies for the treatment of
      resistant hypertension such as renal sympathetic denervation technique has lead
      to a renewed interest in the screening and assessment of prognosis of this
      specific entity which constitutes a subset of uncontrolled hypertension. Its
      prevalence is unknown, but estimated between 12 and 15% among hypertensive
      subjects from the general population. Several factors have been associated with
      the development of resistant hypertension, four of which are essential: age,
      diabetes, chronic kidney disease and vascular structural alteration. Excessive
      salt intake is also a risk factor for poorly controlled hypertension in patients
      with salt-dependent hypertension, and may participate to the genesis of resistant
      hypertension. Because of population ageing and increasing prevalence of diabetes,
      obesity and chronic kidney disease, the prevalence of resistant hypertension is
      expected to rise. A better understanding of its determinants and associated risks
      (such as chronic kidney disease) would identify high-risk groups that may benefit
      from extensive diagnosis work up and more specific treatments.

PMID- 24726613
TI  - Is it possible to define an optimal time for chemotherapy after surgery for
      ovarian cancer?
AB  - OBJECTIVE: The aims of this study are to investigate the actual time from primary
      surgery for epithelial ovarian cancer (OC) to initiation of chemotherapy (TI)
      amongst Danish women in 2005-2006, and to compare the survival for groups with
      early initiation (<=median TI) and late initiation of adjuvant chemotherapy
      (>median TI). METHODS: All Danish women who underwent surgery for OC in the
      period 1 January 2005 to 31 December 2006 and recorded in the Danish
      Gynaecological Cancer Database (DGCD) were included. The five-year survival was
      estimated overall and by TI exposure. The Cox proportional hazard regression
      analysis was used to compute the adjusted hazard ratio (HR). RESULTS: The median
      TI was 32days (25-75% quartile: 24days; 41days). The strongest prognostic factors
      for death were residual tumour and the International Federation of Obstetrics and
      Gynecology (FIGO) stage. The unadjusted HR for death in patients with TI>32days
      compared with TI<=32days was 0.85 (95% CI: 0.70; 1.04), p-value 0.12. When
      adjusted for residual tumour and FIGO-stage the HR was 1.13 (95% CI: 0.92; 1.39),
      p-value 0.26. The overall five-year survival was 42.8%, (95% CI: 38.9%; 46.5%).
      CONCLUSIONS: This nationwide population-based cohort study revealed a non
      significant increased risk of death for patients with TI>32days compared with the
      reference TI<=32days. The strongest prognostic factors were residual tumour after
      surgery and FIGO-stage. The overall five-year survival was 42.8% (95% CI: 38.9%;
      46.5%).

PMID- 24726614
TI  - Dynamic modeling in ovarian cancer: an original approach linking early changes in
      modeled longitudinal CA-125 kinetics and survival to help decisions in early drug
      development.
AB  - OBJECTIVE: Early prediction of the expected benefit of treatment in recurrent
      ovarian cancer (ROC) patients may help in drug development decisions. The actual
      value of 50% CA-125 decrease is being reconsidered. The main objective of the
      present study was to quantify the links between longitudinal assessments of CA
      125 kinetics and progression-free survival (PFS) in treated recurrent ovarian
      cancer (ROC) patients. METHODS: The CALYPSO randomized phase III trial database
      comparing two platinum-based regimens in ROC patients was randomly split into a
      "learning dataset" and a "validation dataset". A parametric survival model was
      developed to associate longitudinal modeled CA-125 changes (DeltaCA125),
      predictive factors, and PFS. The predictive performance of the model was
      evaluated with simulations. RESULTS: The PFS of 534 ROC patients were properly
      characterized by a parametric mathematical model. The modeled DeltaCA125 from
      baseline to week 6 was a better predictor of PFS than the modeled fractional
      change in tumor size. Simulations confirmed the model's predictive performance.
      CONCLUSIONS: We present the first parametric survival model quantifying the
      relationship between PFS and longitudinal CA-125 kinetics in treated ROC
      patients. The model enabled calculation of the increase in DeltaCA125 required to
      observe a predetermined benefit in PFS to compare therapeutic strategies in
      populations. Therefore, DeltaCA125 may be a predictive marker of the expected
      gain in PFS and an early predictive tool in drug development decisions.

PMID- 24726615
TI  - Preoperative quality of life and surgical outcomes in gynecologic oncology
      patients: a new predictor of operative risk?
AB  - OBJECTIVE: Quality of life (QoL) for women with gynecologic malignancies is
      predictive of chemotherapy related toxicity and overall survival but has not been
      studied in relation to surgical outcomes and hospital readmissions. Our goal was
      to evaluate the association between baseline, pre-operative QoL measures and 30
      day post-operative morbidity and health resource utilization by gynecologic
      oncology patients. METHODS: We analyzed prospectively collected survey data from
      an institution-wide cohort study. Patients were enrolled from 8/2012 to 6/2013
      and medical record data was abstracted (demographics, comorbid conditions, and
      operative outcomes). Responses from several validated health-related QoL
      instruments were collected. Bivariate tests and multivariable linear and logistic
      regression models were used to evaluate factors associated with QoL scores.
      RESULTS: Of 182 women with suspected gynecologic malignancies, 152 (84%) were
      surveyed pre-operatively and 148 (81%) underwent surgery. Uterine (94; 63.5%),
      ovarian (26; 17.5%), cervical (15; 10%), vulvar/vaginal (8; 5.4%), and other (5;
      3.4%) cancers were represented. There were 37 (25%) cases of postoperative
      morbidity (PM), 18 (12%) unplanned ER visits, 9(6%) unplanned clinic visits, and
      17 (11.5%) hospital readmissions (HR) within 30days of surgery. On adjusted
      analysis, lower functional well-being scores resulted in increased odds of PM (OR
      1.07, 95%CI 1.01-.1.21) and HR (OR 1.11, 95%CI 1.03-1.19). A subjective global
      assessment score was also strongly associated with HR (OR 1.89, 95%CI 1.14,
      3.16). CONCLUSION: Lower pre-operative QoL scores are significantly associated
      with post-operative morbidity and hospital readmission in gynecologic cancer
      patients. This relationship may be a novel indicator of operative risk.

PMID- 24726616
TI  - Temporal changes in human skeletal muscle and blood lipid composition with fish
      oil supplementation.
AB  - The aim of this study was to examine changes in the lipid profile of red blood
      cells and muscle tissue along with the expression of anabolic signalling proteins
      in human skeletal muscle. Following a 2-week control period, 10 healthy male
      participants consumed 5 g d(-1) of fish oil (FO) for 4 weeks. Muscle biopsies and
      venous blood samples were collected in the fasted state 2 weeks prior (W-2) and
      immediately before (W0) the initiation of FO supplementation for internal
      control. Muscle biopsies and venous blood samples were again obtained at week 1
      (W1), 2 (W2) and 4 (W4) during FO supplementation for assessment of changes in
      lipid composition and expression of anabolic signalling proteins. There was no
      change in the composition of any lipid class between W-2 and W0 confirming
      control. Following FO supplementation n-3 polyunsaturated fatty acid (n-3 PUFA)
      muscle lipid composition was increased from W0 to W2 and continued to rise at W4.
      n-3 PUFA blood lipid composition was increased from W0 to W1 and remained
      elevated for the remaining time points. Total protein content of focal adhesion
      kinase (FAK) increased from W0 to W4 whereas total mechanistic target of
      rapamycin (mTOR) was increased from W0 at W1 with no further significant
      increases at W2 and W4. These data show that FO supplementation results in
      discordant changes in the n-3 PUFA composition of skeletal muscle compared to
      blood that is associated with increases in total FAK content.

PMID- 24726617
TI  - Imatinib inhibits the expression of SCO2 and FRATAXIN genes that encode
      mitochondrial proteins in human Bcr-Abl+ leukemia cells.
AB  - Imatinib mesylate (IM/Gleevec(r)), a selective inhibitor of chimeric Bcr-Abl
      tyrosine kinase, was developed as a first line drug to treat CML and ALL Ph(+)
      patients. Earlier studies have shown that hemin counteracts the IM-induced cell
      killing in human K-562 CML cells. In this study, we investigated whether IM
      disrupts the heme-dependent Cytochrome c Oxidase (COX) Biosynthesis and Assembly
      Pathway (HDCBAP) in Bcr-Abl(+) and Bcr-Abl(-) cells by affecting the expression
      of key-genes. Cells were exposed to IM and evaluated at time intervals for cell
      growth, cell death, expression of various genes by RT-PCR analysis as well as
      Sco2 mature protein levels by western blot analysis and COX enzymatic activity.
      IM at 1 MUM induced extensive cell growth inhibition and cell death as well as
      marked suppression of the expression of SCO2 and FRATAXIN (FXN) genes in human K
      562 and KU-812 Bcr-Abl(+) CML cells. IM also reduced the protein level of mature
      Sco2 mitochondrial protein as well as COX activity in these cell lines. However,
      treatment of human MOLT-4 Bcr-Abl(-) cells with 1MUM and even with higher
      concentrations (4*10(-5)M) of IM neither reduced the expression of SCO2 and FXN
      genes nor suppressed the protein level of mature Sco2 protein and COX activity.
      Our findings indicate that SCO2 and FXN genes, involved in HDCBAP, are repressed
      by IM in human Bcr-Abl(+) CML cells and may represent novel target sites in
      leukemia therapy.

PMID- 24726618
TI  - Risk factors for repeat abortion and implications for addressing unintended
      pregnancy in Vietnam.
AB  - OBJECTIVE: To determine predictors of repeat abortion in 3 provinces in Vietnam.
      METHODS: In a cross-sectional study between August and December 2011, women who
      underwent abortion were interviewed after the procedure in 62 public health
      facilities in Hanoi, Khanh Hoa, and Ho Chi Minh City (HCMC). Information on
      sociodemographic factors, contraceptive and reproductive history and intentions,
      and opinions and experience of abortion services was collected. The primary
      outcome was repeat (>=2) abortions. RESULTS: Overall, 1224 women were
      interviewed: 534 from Hanoi, 163 from Khanh Hoa, and 527 from HCMC. The mean age
      and parity of the respondents were 29 years and 1.8, respectively, and 79.6% were
      married. Approximately half of the respondents were not using contraception
      before pregnancy. The prevalence of repeat abortion was 31.7%. In multivariate
      models, significant predictors of repeat abortion included living in Hanoi,
      higher parity, age 35 years or older, and having 2 or more daughters (versus 1)
      or no sons (versus 1) after controlling for parity (all P < 0.05). CONCLUSION:
      Repeat abortion remains high in Vietnam, fueled partly by inadequate
      contraceptive use. Son preference seems to be an important predictor of repeat
      abortion. Strengthening post-abortion contraceptive counseling and promoting long
      acting contraceptive methods are essential to reduce repeat abortion.

PMID- 24726619
TI  - Long-term follow-up and recurrence rate after mesorectum-sparing bowel resection
      among women with rectovaginal endometriosis.
AB  - OBJECTIVE: To demonstrate the quality of a combined vaginal-abdominal surgical
      approach to rectovaginal endometriosis by analyzing long-term outcome and
      recurrence rates. METHODS: In a prospective cohort study in Berlin, Germany,
      women with endometriosis of the rectovaginal septum were enrolled between
      September 2004 and December 2012. Bowel infiltration was verified
      intraoperatively and treated by a nerve-sparing, mesentery-preserving vaginal
      abdominal operative approach. Operative results were evaluated by assessing short
      and long-term complications and recurrence rates. RESULTS: During the study
      period, 110 women underwent surgery. For 71 (64.5%) patients, bowel infiltration
      was confirmed intraoperatively. Overall, 15% of the patients had peri- or
      postoperative complications. No long-term complications occurred. After a median
      follow-up of 64 months, no recurrence in the rectovaginal septum was observed
      among the study patients. The recurrence of pelvic endometriosis was 15%.
      CONCLUSION: The surgical nerve-sparing approach to rectovaginal endometriosis was
      confirmed to facilitate precise diagnosis and treatment with minimal morbidity
      and a long-term complication rate of 0%.

PMID- 24726620
TI  - Risk factors for human papillomavirus persistence among women undergoing cold
      knife conization for treatment of high-grade cervical intraepithelial neoplasia.
AB  - OBJECTIVE: To investigate the risk factors potentially associated with high-risk
      human papillomavirus (HPV) persistence in women undergoing cold-knife conization
      (CKC) for treatment of high-grade cervical intraepithelial neoplasia (CIN).
      METHODS: Medical records of women who underwent CKC for treatment of CIN 2/3
      between 2007 and 2012 at a tertiary hospital in Ankara, Turkey, were
      retrospectively analyzed. Cases involving persistent HPV infection after 1 year
      of follow-up were identified. Using univariate and multivariate analyses, the
      impact of various factors such as patient age, menopausal status, parity, high
      risk HPV type, excised cone dimensions (width, height, and depth), and surgical
      margin status on high-risk HPV persistence was assessed. RESULTS: A total of 292
      women underwent CKC for treatment of CIN 2/3 within the study period. After women
      with a subsequent diagnosis of cervical cancer, subsequent total hysterectomy,
      and inadequate follow-up data were eliminated, 113 women were eligible for final
      analysis. High-risk HPV persistence was detected in 24 (21.2%) women, and
      multivariate analysis revealed that patient age and cone depth were significant
      independent predictors (P < 0.05). CONCLUSION: High-risk HPV persistence may be
      encountered after CKC procedures. It is important to evaluate persistent HPV
      infections after treatment because affected women are at increased risk for
      disease persistence, recurrence, and progression.

PMID- 24726622
TI  - Purification and characterization of 6-phosphogluconate dehydrogenase from the
      wing-polymorphic cricket, Gryllus firmus, and assessment of causes of morph
      differences in enzyme activity.
AB  - Considerable information exists on the physiological correlates of life history
      adaptation, while molecular data on this topic are rapidly accumulating. However,
      much less is known about the enzymological basis of life history adaptation in
      outbred populations. In the present study, we compared developmental profiles of
      fat body specific activity, kinetic constants of homogeneously purified and
      unpurified enzyme, and fat body enzyme concentration of the pentose-shunt enzyme,
      6-phosphogluconate dehydrogenase (6PGDH, E.C.1.1.1.44) between the dispersing
      [long-winged, LW(f)] and flightless [short-winged, SW] genotypes of the cricket
      Gryllus firmus. Neither kcat nor the Michaelis constant for 6-phosphogluconate
      differed between 6PGDH from LW(f) versus SW morphs for either homogeneously
      purified or unpurified enzyme. Purified enzyme from the LW(f) morph exhibited
      reduced KM for NADP(+), but this was not observed for multiple KM(NADP+)
      estimates for unpurified enzyme. A polyclonal antibody was generated against
      6PGDH which was used to develop a chemiluminescence assay to quantify 6PGDH
      concentration in fat body homogenates. Elevated enzyme concentration accounted
      for all of the elevated 6PGDH specific activity in the LW(f) morph during the
      juvenile and adult stages. Finally, activity of another pentose-shunt enzyme,
      glucose-6-phosphate dehydrogenase, strongly covaried with 6PGDH activity
      suggesting that variation in 6PGDH activity gives rise to variation in pentose
      shunt flux. This is one of the first life-history studies and one of the few
      studies of intraspecific enzyme adaptation to identify the relative importance of
      evolutionary change in enzyme concentration vs. kinetic constants to adaptive
      variation in enzyme activity in an outbred population. 

PMID- 24726621
TI  - Cytokine gene variations associated with subsyndromal depressive symptoms in
      patients with breast cancer.
AB  - PURPOSE: This study explored the relationships between variations in cytokines
      genes and depressive symptoms in a sample of patients who were assessed prior to
      and for six months following breast cancer surgery. Phenotypic differences
      between Resilient (n = 155) and Subsyndromal (n = 180) depressive symptom
      classes, as well as variations in cytokine genes were evaluated. METHOD: Patients
      were recruited prior to surgery and followed for six months. Growth mixture
      modeling was used to identify distinct latent classes based on Center for
      Epidemiological Studies Depression (CES-D) Scale scores. Eighty-two single
      nucleotide polymorphisms and 35 haplotypes among 15 candidate cytokine genes were
      evaluated. RESULTS: Patients in the Subsyndromal class were significantly
      younger, more likely to be married or partnered, and reported a significantly
      lower functional status. Variation in three cytokine genes (i.e., interferon
      gamma receptor 1 (IFNGR1 rs9376268), interleukin 6 (IL6 rs2069840), tumor
      necrosis factor alpha (TNFA rs1799964)), as well as age and functional status
      predicted membership in the Subsyndromal versus the Resilient class. CONCLUSIONS:
      A variation in TNFA that was associated with Subsyndromal depressive symptoms in
      a sample of patients and their family caregivers was confirmed in this sample.
      Variations in cytokine genes may place these patients at higher risk for the
      development of Subsyndromal levels of depressive symptoms.

PMID- 24726623
TI  - Two arginine kinases of Tetrahymena pyriformis: characterization and
      localization.
AB  - Two cDNAs, one coding a typical 40-kDa arginine kinase (AK1) and the other coding
      a two-domain 80-kDa enzyme (AK2), were isolated from ciliate Tetrahymena
      pyriformis, and their recombinant enzymes were successfully expressed in
      Escherichia coli. Both enzymes had an activity comparable to those of typical
      invertebrate AKs. Interestingly, the amino acid sequence of T. pyriformis AK1,
      but not AK2, had a distinct myristoylation signal sequence at the N-terminus,
      suggesting that 40-kDa AK1 targets the membrane. Moreover, Western blot analysis
      showed that the AK1 is mainly localized in the ciliary fraction. Based on these
      results, we discuss the phosphoarginine shuttle, which enables a continuous
      energy flow to dynein for ciliary movement in T. pyriformis, and the role of AK1
      in this model. 

PMID- 24726624
TI  - Enhancing food safety management in Taiwan.

PMID- 24726625
TI  - A training platform for many-dimensional prosthetic devices using a virtual
      reality environment.
AB  - Brain machine interfaces (BMIs) have the potential to assist in the
      rehabilitation of millions of patients worldwide. Despite recent advancements in
      BMI technology for the restoration of lost motor function, a training environment
      to restore full control of the anatomical segments of an upper limb extremity has
      not yet been presented. Here, we develop a virtual upper limb prosthesis with 27
      independent dimensions, the anatomical dimensions of the human arm and hand, and
      deploy the virtual prosthesis as an avatar in a virtual reality environment (VRE)
      that can be controlled in real-time. The prosthesis avatar accepts kinematic
      control inputs that can be captured from movements of the arm and hand as well as
      neural control inputs derived from processed neural signals. We characterize the
      system performance under kinematic control using a commercially available motion
      capture system. We also present the performance under kinematic control achieved
      by two non-human primates (Macaca Mulatta) trained to use the prosthetic avatar
      to perform reaching and grasping tasks. This is the first virtual prosthetic
      device that is capable of emulating all the anatomical movements of a healthy
      upper limb in real-time. Since the system accepts both neural and kinematic
      inputs for a variety of many-dimensional skeletons, we propose it provides a
      customizable training platform for the acquisition of many-dimensional neural
      prosthetic control. 

PMID- 24726626
TI  - [Bioaccumulation of Giardia and Cryptosporidium coproantigen in a child's human
      environment].

PMID- 24726627
TI  - [Cerebral oximetry in the management of ductus arteriosus].

PMID- 24726628
TI  - Identification of incident CKD stage 3 in research studies.
AB  - BACKGROUND: In epidemiologic research, incident chronic kidney disease (CKD)
      commonly is determined by laboratory tests performed at planned study visits.
      Given the morbidity and mortality associated with CKD, persons with incident
      disease may be less likely to attend scheduled visits, affecting observed
      associations. The objective of this study was to quantify loss to follow-up by
      CKD status and determine whether supplementation with diagnostic code data
      improves capture of incident CKD. STUDY DESIGN: Prospective cohort study. SETTING
      & PARTICIPANTS: 11,560 participants in the Atherosclerosis Risk in Communities
      (ARIC) Study underwent continuous surveillance for hospitalizations and death
      from baseline visit (1996-1999) to follow-up visit (2011-2013). A subset of
      hospitalizations in Washington County, MD, was used in diagnostic code validation
      (n=2,540). PREDICTOR: Baseline demographics and comorbid conditions. OUTCOMES:
      Incident CKD stage 3 ascertained by follow-up visit (visit-based definition) or
      hospitalization surveillance (hospitalization-based definition). MEASUREMENTS:
      Visit-based definition: >=25% decline from baseline estimated glomerular
      filtration rate to <60 mL/min/1.73 m2 at follow-up visit; hospitalization-based
      definition: hospitalization CKD diagnostic code. RESULTS: Of 11,560 participants,
      5,951 attended the follow-up visit and 9,264 were hospitalized. Never
      hospitalized participants were younger, more often female, and had fewer comorbid
      conditions; 73.5% attended the follow-up visit. Incident CKD stage 3 occurred in
      1,172 participants by the visit-based definition (251 were never hospitalized)
      and 1,078 participants by the hospitalization-based definition (237 attended the
      follow-up study visit). Sensitivity of the hospitalization-based CKD definition
      was 35.5% (95% CI, 31.6%-39.7%); specificity was 95.7% (95% CI, 94.2%-96.8%).
      Sensitivity was higher with later time period, older participant age, and
      baseline prevalent diabetes and CKD. LIMITATIONS: A subset of hospitalizations
      was used for validation; 15-year gap between study visits. CONCLUSIONS: The
      sensitivity of diagnostic code-identified CKD is low and varies by certain
      factors; however, supplementing a visit-based definition with hospitalization
      information can increase disease identification during periods of follow-up
      without study visits.

PMID- 24726630
TI  - Bone disease in CKD: a focus on osteoporosis diagnosis and management.
AB  - Osteoporosis is defined as a condition of impairment in bone strength due to low
      bone mineral density and poor bone quality and predisposes individuals to an
      increased risk of fractures. Osteoporosis may coexist with chronic kidney disease
      mineral and bone disorder (CKD-MBD) and osteoporotic fractures occur in all
      stages of CKD. Management of osteoporosis in CKD should consider the
      pathophysiology of both disorders. Diagnosis and management of osteoporosis in
      patients with stages 1-3 CKD and patients without CKD are similar, but diagnosis
      and management decisions differ greatly once patients have stages 4-5 CKD.
      Discriminating between osteoporosis and CKD-MBD is best accomplished with
      quantitative bone histomorphometry. Biochemical markers, especially intact
      parathyroid hormone and bone-specific alkaline phosphatase, also may be helpful.
      When the diagnosis of osteoporosis is established, management in stages 4-5 CKD
      may include antiresorptive or anabolic agents, though evidence for efficacy is
      marginal in advanced CKD. 

PMID- 24726629
TI  - Serum testosterone levels and mortality in men with CKD stages 3-4.
AB  - BACKGROUND: Hypogonadism in men (total testosterone <350 ng/dL) is associated
      with higher risk of cardiovascular disease and mortality in men on dialysis
      therapy. We evaluated the association of hypogonadism with all-cause mortality in
      men with non-dialysis-dependent chronic kidney disease (CKD). STUDY DESIGN:
      Retrospective, cohort study. SETTING & PARTICIPANTS: 2,419 men with CKD stages 3
      4 (estimated glomerular filtration rate, 15-59 mL/min/1.73 m2) who had total
      testosterone measured for cause between January 1, 2005, and October 31, 2011, at
      a tertiary-care center in Cleveland, OH. PREDICTORS: Total testosterone measured
      using an immunoassay measurement in 3 forms: (1) categorized as low or
      testosterone replacement therapy versus normal, (2) continuous log testosterone,
      and (3) quintiles (100-226, 227-305, 306-392, 393-511, and 512-3,153 ng/dL).
      OUTCOMES: Factors associated with low total testosterone level and the
      association between low total testosterone level and all-cause mortality were
      evaluated using logistic regression, Cox proportional hazard models, and Kaplan
      Meier survival curves. RESULTS: Hypogonadism was found in 1,288 of 2,419 (53%)
      men. In a multivariable logistic regression analysis, African American ethnicity
      and higher estimated glomerular filtration rate were associated with lower odds
      of having hypogonadism. Diabetes and higher body mass index were associated with
      higher odds of having hypogonadism. 357 of 2,419 (15%) patients died during a
      median follow-up of 2.3 years. In the multivariate Cox model, testosterone level
      <350 ng/dL or testosterone replacement therapy was not associated with mortality.
      In a multivariable model also adjusted for testosterone supplementation, higher
      log testosterone was associated with significantly lower mortality (HR per 1 log
      unit, 0.70; 95% CI, 0.55-0.89). When compared to the highest quintile, the second
      lowest quintile of testosterone was associated with higher mortality (HR, 1.53;
      95% CI, 1.09-2.16). LIMITATIONS: Single-center study, timing of testosterone
      testing, lack of adjustment for proteinuria, and sampling bias. CONCLUSIONS: Low
      total testosterone level may be associated with higher mortality in men with CKD
      stages 3-4, but more studies are needed.

PMID- 24726631
TI  - Do cyclodextrins bound to dextran microspheres act as sustained delivery systems
      of drugs?
AB  - The use of cyclodextrins (CDs) for controlled delivery of drugs is largely
      presented in the literature. However, the question of whether CDs themselves
      linked to a polymeric network are able to sustain the release of drugs still
      persists. Here, CD immobilization within dextran microspheres is reported, and CD
      dextran complexes were packed in a glass column and then, the retention time of
      different drugs and drug model compounds was determined by liquid chromatography.
      The release profiles of drugs and of drug model compounds (indole, 3-nitrophenol,
      p-hydroxybenzoic acid, diclofenac), characterized by different values of the
      retention time (high, moderate or low), were investigated. The release rates were
      quite high even for drugs that exhibit very high retention time (high association
      equilibrium constant). Moreover, the volume of the release fluid strongly
      influences the rate of drug release. As a whole, "the sink conditions" must be
      continuously maintained, since at each drug concentration in the release medium,
      equilibrium occurs between the free and the CD-bound drug. 

PMID- 24726632
TI  - Quantifying the release of lactose from polymer matrix tablets with an
      amperometric biosensor utilizing cellobiose dehydrogenase.
AB  - The release of lactose (hydrophilic) from polymer tablets made with
      hydrophobically modified poly(acrylic acid) (HMPAA) have been studied and
      compared to the release of ibuprofen, a hydrophobic active substance. Lactose is
      one of the most used excipients for tablets, but lactose release has not been
      widely studied. One reason could be a lack of good analytical tools. A novel
      biosensor with cellobiose dehydrogenase (CDH) was used to detect the lactose
      release, which has a polydiallyldimethylammonium chloride (PDADMAC) layer that
      increases the response. A sample treatment using polyethylenimine (PEI) was
      developed to eliminate possible denaturants. The developed methodology provided a
      good approach to detect and quantify the released lactose. The release was
      studied with or without the presence of a model amphiphilic substance, sodium
      dodecyl sulphate (SDS), in the release medium. Ibuprofen showed very different
      release rates in the different media, which was attributed to hydrophobic
      interactions between the drug, the HMPAA and the SDS in the release medium. The
      release of hydrophilic lactose, which did not associate to any of the other
      components, was rapid and showed only minor differences. The new methodology
      provides a useful tool to further evaluate tablet formulations by a relatively
      simple set of experiments. 

PMID- 24726633
TI  - NMR cryoporometry characterisation studies of the relation between drug release
      profile and pore structural evolution of polymeric nanoparticles.
AB  - PLGA/PLA polymeric nanoparticles could potentially enhance the effectiveness of
      convective delivery of drugs, such as carboplatin, to the brain, by enabling a
      more sustained dosage over a longer time than otherwise possible. However, the
      link between the controlled release nanoparticle synthesis route, and the
      subsequent drug release profile obtained, is not well-understood, which hinders
      design of synthesis routes and availability of suitable nanoparticles. In
      particular, despite pore structure evolution often forming a key aspect of past
      theories of the physical mechanism by which a particular drug release profile is
      obtained, these theories have not been independently tested and validated against
      pore structural information. Such validation is required for intelligent
      synthesis design, and NMR cryoporometry can supply the requisite information.
      Unlike conventional pore characterisation techniques, NMR cryoporometry permits
      the investigation of porous particles in the wet state. NMR cryoporometry has
      thus enabled the detailed study of the evolving, nanoscale structure of
      nanoparticles during drug release, and thus related pore structure to drug
      release profile in a way not done previously for nanoparticles. Nanoparticles
      with different types of carboplatin drug release profiles were compared,
      including burst release, and various forms of delayed release. ESEM and TEM
      images of these nanoparticles also provided supporting data showing the rapid
      initial evolution of some nanoparticles. Different stages, within a complex,
      varying drug release profile, were found to be associated with particular types
      of changes in the nanostructure which could be distinguished by NMR. For a core
      coat nanoparticle formulation, the development of smaller nanopores, following an
      extended induction period with no structural change, was associated with the
      onset of substantial drug release. This information could be used to
      independently validate the rationale for a particular synthesis method. Hence,
      the specific reasons for the effectiveness of the synthesis route, for obtaining
      core-coat nanoparticles with delayed release, have been elucidated. 

PMID- 24726634
TI  - Evaluating optimal combination of clodronate and bioactive glass for dental
      application.
AB  - Both clodronate and bioactive glass are mostly used alone as treatment in various
      bone diseases but, they are also known to have beneficial effects in dental
      application. The same processes that lead to loss of bone can also result in
      alveolar bone loss. The object of this study was to define the optimal
      combination of clodronate and bioactive glass (BAG) to be used locally in
      dentistry. The evaluation was based on measurements and solid state properties
      obtained with pH, scanning electron microscopy (SEM), differential scanning
      calorimetric (DSC), X-ray powder diffraction (XRPD), Fourier transform infrared
      spectroscopy (FTIR) and Focused-ion beam (FIB) and energy dispersive X-ray
      spectroscopic (EDS) mapping. The results indicate that if too much calcium
      clodronate precipitation is formed, the activity of BAG is affected negatively.
      As there is more reaction surface to form calcium clodronate, similar to the
      amount of clodronate present, this reduces the bioactivity of BAG. Therefore, in
      dental treatment the most suitable BAG and clodronate combination product would
      have apatite (HA, hydroxyapatite) formation ability and amount of clodronate
      enough to enhance the bioactivity of BAG allowing HA formation. Based on
      combinations investigated, the one with 200mg clodronate and 1 g BAG with
      particle size 0.5-0.8 mm was chosen to be the most promising for local dental
      application.

PMID- 24726635
TI  - Impact of perioperative blood pressure variability on health resource utilization
      after cardiac surgery: an analysis of the ECLIPSE trials.
AB  - OBJECTIVE: To examine the impact of blood pressure control on hospital health
      resource utilization using data from the ECLIPSE trials. DESIGN: Post-hoc
      analysis of data from 3 prospective, open-label, randomized clinical trials
      (ECLIPSE trials). SETTING: Sixty-one medical centers in the United States.
      PARTICIPANTS: Patients 18 years or older undergoing cardiac surgery.
      INTERVENTIONS: Clevidipine was compared with nitroglycerin, sodium nitroprusside,
      and nicardipine. MEASUREMENTS AND MAIN RESULTS: The ECLIPSE trials included 3
      individual randomized open-label studies comparing clevidipine to nitroglycerin,
      sodium nitroprusside, and nicardipine. Blood pressure control was assessed as the
      integral of the cumulative area under the curve (AUC) outside specified systolic
      blood pressure ranges, such that lower AUC represents less variability. This
      analysis examined surgery duration, time to extubation, as well as intensive care
      unit (ICU) and hospital length of stay (LOS) in patients with AUC<=10 mmHg*min/h
      compared to patients with AUC>10 mmHg*min/h. One thousand four hundred ten
      patients were included for analysis; 736 patients (52%) had an AUC<=10
      mmHg*min/h, and 674 (48%) had an AUC>10 mmHg*min/h. The duration of surgery and
      ICU LOS were similar between groups. Time to extubation and postoperative LOS
      were both significantly shorter (p = 0.05 and p<0.0001, respectively) in patients
      with AUC<=10. Multivariate analysis demonstrates AUC<=10 was significantly and
      independently associated with decreased time to extubation (hazard ratio 1.132, p
      = 0.0261) and postoperative LOS (hazard ratio 1.221, p = 0.0006). CONCLUSIONS:
      Based on data derived from the ECLIPSE studies, increased perioperative BP
      variability is associated with delayed time to extubation and increased
      postoperative LOS.

PMID- 24726636
TI  - Iron deficiency in Crohn's disease: iron supplementation or disease control?

PMID- 24726637
TI  - Reduction of seclusion on a hospital-wide level: successful implementation of a
      less restrictive policy.
AB  - PURPOSE: Change of treatment policy from closed to open ward settings has been
      shown to reduce coercive measures. The aim of the current study was to examine
      the effects of the change from closed to open wards on the frequency of seclusion
      and forced medication in a hospital-wide setting. SUBJECTS AND METHODS: 2-year,
      longitudinal observational study with 2838 inpatient cases. RESULTS: On a
      hospital-wide level, the percentage of patients with at least one seclusion was
      decreased significantly (chi(2)(1) = 5.8; p = .016), while there was no
      significant change in forced medication (chi(2)(1) = .08; p = .775). The
      frequency of seclusions and forced medication decreased significantly on newly
      opened wards, and there were no significant changes regarding seclusion on
      permanently closed or open wards, while the number of forced medications
      increased significantly on closed wards. The decrease in seclusions on newly
      opened wards remained statistically significant after controlling for diagnoses
      and severity of illness. DISCUSSION: Our results indicate that a reduction of
      overall seclusion can be successfully attained, and that, in particular, the
      frequency of seclusion and forced medication on newly opened wards was decreased
      significantly. These changes were not accompanied by a significant increase in
      seclusion on other wards. CONCLUSION: Open ward treatment was successfully
      implemented and was associated with a significant decrease of coercive measures
      in our study. It might therefore provide a good care model, strengthening the
      patient's right to autonomy and leading to a reduction of coercive measures.

PMID- 24726638
TI  - Prenatal and perinatal risk factors in a twin study of autism spectrum disorders.
AB  - INTRODUCTION: Multiple studies associate prenatal and perinatal complications
      with increased risks for autism spectrum disorders (ASDs). The objectives of this
      study were to utilize a twin study design to 1) Investigate whether shared
      gestational and perinatal factors increase concordance for ASDs in twins, 2)
      Determine whether individual neonatal factors are associated with the presence of
      ASDs in twins, and 3) Explore whether associated factors may influence males and
      females differently. METHODS: Data from medical records and parent response
      questionnaires from 194 twin pairs, in which at least one twin had an ASD, were
      analyzed. RESULTS: Shared factors including parental age, prenatal use of
      medications, uterine bleeding, and prematurity did not increase concordance risks
      for ASDs in twins. Among the individual factors, respiratory distress
      demonstrated the strongest association with increased risk for ASDs in the group
      as a whole (OR 2.11, 95% CI 1.27-3.51). Furthermore, respiratory distress (OR
      2.29, 95% CI 1.12-4.67) and other markers of hypoxia (OR 1.99, 95% CI 1.04-3.80)
      were associated with increased risks for ASDs in males, while jaundice was
      associated with an increased risk for ASDs in females (OR 2.94, 95% CI 1.28
      6.74). CONCLUSIONS: Perinatal factors associated with respiratory distress and
      other markers of hypoxia appear to increase risk for autism in a subgroup of
      twins. Future studies examining potential gender differences and additional
      prenatal, perinatal and postnatal environmental factors are required for
      elucidating the etiology of ASDs and suggesting new methods for treatment and
      prevention.

PMID- 24726639
TI  - Neurophysiologic predictors of response to atomoxetine in young adults with
      attention deficit hyperactivity disorder: a pilot project.
AB  - Atomoxetine is a non-stimulant medication with sustained benefit throughout the
      day, and is a useful pharmacologic treatment option for young adults with
      Attention-Deficit/Hyperactivity Disorder (ADHD). It is difficult to determine,
      however, those patients for whom atomoxetine will be both effective and
      advantageous. Patients may need to take the medication for several weeks before
      therapeutic benefit is apparent, so a biomarker that could predict atomoxetine
      effectiveness early in the course of treatment could be clinically useful. There
      has been increased interest in the study of thalamocortical oscillatory activity
      using quantitative electroencephalography (qEEG) as a biomarker in ADHD. In this
      study, we investigated qEEG absolute power, relative power, and cordance, which
      have been shown to predict response to reuptake inhibitor antidepressants in
      Major Depressive Disorder (MDD), as potential predictors of response to
      atomoxetine. Forty-four young adults with ADHD (ages 18-30) enrolled in a multi
      site, double-blind placebo-controlled study of the effectiveness of atomoxetine
      and underwent serial qEEG recordings at pretreatment baseline and one week after
      the start of medication. qEEG measures were calculated from a subset of the
      sample (N = 29) that provided useable qEEG recordings. Left temporoparietal
      cordance in the theta frequency band after one week of treatment was associated
      with ADHD symptom improvement and quality of life measured at 12 weeks in
      atomoxetine-treated subjects, but not in those treated with placebo. Neither
      absolute nor relative power measures selectively predicted improvement in
      medication-treated subjects. Measuring theta cordance after one week of treatment
      could be useful in predicting atomoxetine treatment response in adult ADHD. 

PMID- 24726640
TI  - Genomic aberrations of BRCA1-mutated fallopian tube carcinomas.
AB  - Intraepithelial carcinomas of the fallopian tube are putative precursors to high
      grade serous carcinomas of the ovary and peritoneum. Molecular characterization
      of these early precursors is limited but could be the key to identifying tumor
      biomarkers for early detection. This study presents a genome-wide copy number
      analysis of occult fallopian tube carcinomas identified through risk-reducing
      prophylactic oophorectomy from three women with germline BRCA1 mutations,
      demonstrating that extensive genomic aberrations are already established at this
      early stage. We found no indication of a difference in the level of genomic
      aberration observed in fallopian tube carcinomas compared with high-grade serous
      ovarian carcinomas. These findings suggest that spread to the peritoneal cavity
      may require no or very little further tumor evolution, which raises the question
      of what is the real window of opportunity to detect high-grade serous peritoneal
      carcinoma arising from the fallopian tube before it spreads. Nonetheless, the
      similarity of the genomic aberrations to those observed in high-grade serous
      ovarian carcinomas suggests that genetic biomarkers identified in late-stage
      disease may be relevant for early detection. 

PMID- 24726641
TI  - Differential muscle hypertrophy is associated with satellite cell numbers and Akt
      pathway activation following activin type IIB receptor inhibition in Mtm1 p.R69C
      mice.
AB  - X-linked myotubular myopathy is a congenital myopathy caused by deficiency of
      myotubularin. Patients often present with severe perinatal weakness, requiring
      mechanical ventilation to prevent death from respiratory failure. We recently
      reported that an activin receptor type IIB inhibitor produced hypertrophy of type
      2b myofibers and modest increases of strength and life span in the severely
      myopathic Mtm1delta4 mouse model of X-linked myotubular myopathy. We have now
      performed a similar study in the less severely symptomatic Mtm1 p.R69C mouse in
      hopes of finding greater treatment efficacy. Activin receptor type IIB inhibitor
      treatment of Mtm1 p.R69C animals produced behavioral and histological evidence of
      hypertrophy in gastrocnemius muscles but not in quadriceps or triceps. The
      ability of the muscles to respond to activin receptor type IIB inhibitor
      treatment correlated with treatment-induced increases in satellite cell number
      and several muscle-specific abnormalities of hypertrophic signaling. Treatment
      responsive Mtm1 p.R69C gastrocnemius muscles displayed lower levels of
      phosphorylated ribosomal protein S6 and higher levels of phosphorylated
      eukaryotic elongation factor 2 kinase than were observed in Mtm1 p.R69C
      quadriceps muscle or in muscles from wild-type littermates. Hypertrophy in the
      Mtm1 p.R69C gastrocnemius muscle was associated with increased levels of
      phosphorylated ribosomal protein S6. Our findings indicate that muscle-, fiber
      type-, and mutation-specific factors affect the response to hypertrophic
      therapies that will be important to assess in future therapeutic trials. 

PMID- 24726642
TI  - TLR9 agonist regulates angiogenesis and inhibits corneal neovascularization.
AB  - Myeloid cells are highly adaptable and may positively or negatively regulate
      angiogenesis dependent on the cognate and soluble signals they receive. Toll-like
      receptors (TLRs) initiate immune responses, orchestrate adaptive immune
      responses, and regulate vascular endothelial growth factor (VEGF)-mediated
      angiogenesis during wound healing. We investigated the possible role of TLR
      ligands in attenuation of new vessel growth via regulation of expression of VEGF
      or soluble fms-like tyrosine kinase-1 (sFlt-1) in both an aortic ring assay and a
      model of suture-induced corneal angiogenesis. The TLR3 ligand [poly(I:C)]
      markedly suppressed VEGF secretion and stimulated sFlt-1 release from
      macrophages. The aortic ring assay demonstrated that new vessels were promoted by
      the TLR2 ligand (heat killed Listeria monocytogenes) and the TLR4 ligand
      (lipopolysaccharide), concomitant with increased VEGF and matrix
      metalloproteinase 9 secretion. In contrast, the TLR9 ligand [oligodeoxynucleotide
      (ODN)1826] stimulated sFlt-1 secretion from macrophages and reduced the number of
      aortic ring vessel sprouts. ODN1826 also significantly reduced the length and
      volume of both hemangiogenesis and lymphangiogenesis in the suture-induced
      corneal angiogenesis model. Furthermore, 53 angiogenic factors were examined via
      protein array and compared between ODN1826- and water-treated corneas to
      interrogate the pathway of ODN1826 inhibition, demonstrating an up-regulation of
      Serpin E1 signal. Further clinical and IHC analyses of the aortic ring assay
      indicated that TLR9 suppressed tip cell migration and recruitment of mural cells
      and adventitial macrophages. 

PMID- 24726643
TI  - Methuosis: nonapoptotic cell death associated with vacuolization of macropinosome
      and endosome compartments.
AB  - Apoptosis is the most widely recognized form of physiological programmed cell
      death. During the past three decades, various nonapoptotic forms of cell death
      have gained increasing attention, largely because of their potential importance
      in pathological processes, toxicology, and cancer therapy. A recent addition to
      the panoply of cell death phenotypes is methuosis. The neologism is derived from
      the Greek methuo (to drink to intoxication) because the hallmark of this form of
      cell death is displacement of the cytoplasm by large fluid-filled vacuoles
      derived from macropinosomes. The demise of the cell resembles many forms of
      necrosis, insofar as there is a loss of metabolic capacity and plasma membrane
      integrity, without the cell shrinkage and nuclear fragmentation associated with
      apoptosis. Methuosis was initially defined in glioblastoma cells after ectopic
      expression of activated Ras, but recent reports have described small molecules
      that can induce the features of methuosis in a broad spectrum of cancer cells,
      including those that are resistant to conventional apoptosis-inducing drugs. This
      review summarizes the available information about the distinguishing
      morphological characteristics and underlying mechanisms of methuosis. We compare
      and contrast methuosis with other cytopathological conditions in which
      accumulation of clear cytoplasmic vacuoles is a prominent feature. Finally, we
      highlight key questions that need to be answered to determine whether methuosis
      truly represents a unique form of regulated cell death. 

PMID- 24726644
TI  - IRF-3, IRF-7, and IPS-1 promote host defense against acute human metapneumovirus
      infection in neonatal mice.
AB  - Human metapneumovirus (hMPV) is a leading cause of respiratory tract disease in
      children and is associated with acute bronchiolitis, pneumonia, and asthma
      exacerbations, yet the mechanisms by which the host immune response to hMPV is
      regulated are poorly understood. By using gene-deleted neonatal mice, we examined
      the contributions of the innate receptor signaling molecules interferon (IFN)
      beta promoter stimulator 1 (IPS-1), IFN regulatory factor (IRF) 3, and IRF7.
      Viral load in the lungs was markedly greater in IPS-1(-/-) > IRF3/7(-/-) > IRF3(
      /-), but not IRF7(-/-), mice compared with wild-type mice. IFN-beta and IFN
      lambda2/3 (IL-28A/B) production was attenuated in the bronchoalveolar lavage
      fluid in all factor-deficient mice compared with wild-type mice at 1 day after
      infection, although IFN-lambda2/3 was greater in IRF3/7(-/-) mice at 5 days after
      infection. IRF7(-/-) and IRF3/7(-/-) mice presented with airway eosinophilia,
      whereas only IRF3/7(-/-) mice developed an exaggerated type 1 and 17 helper T
      cell response, characterized by natural killer T-cell and neutrophilic
      inflammation. Despite having the highest viral load, IPS-1(-/-) mice did not
      develop a proinflammatory cytokine or granulocytic response to hMPV infection.
      Our findings demonstrate that IFN-beta, but not IFN-lambda2/3, produced via an
      IPS-1-IRF3 signaling pathway, is important for hMPV clearance. In the absence of
      a robust type I IFN-alpha/beta response, targeting the IPS-1 signaling pathway
      may limit the overexuberant inflammatory response that occurs as a consequence of
      viral persistence. 

PMID- 24726645
TI  - RB tumor suppressive function in response to xenobiotic hepatocarcinogens.
AB  - Diverse etiologic events are associated with the development of hepatocellular
      carcinoma. During hepatocarcinogenesis, genetic events likely occur that
      subsequently cooperate with long-term exposures to further drive the progression
      of hepatocellular carcinoma. In this study, the frequent loss of the
      retinoblastoma (RB) tumor suppressor in hepatocellular carcinoma was modeled in
      response to diverse hepatic stresses. Loss of RB did not significantly affect the
      response to a steatotic stress as driven by a methionine- and choline-deficient
      diet. In addition, RB status did not significantly influence the response to
      peroxisome proliferators that can drive hepatomegaly and tumor development in
      rodents. However, RB loss exhibited a highly significant effect on the response
      to the xenobiotic1,4-Bis-[2-(3,5-dichloropyridyloxy)] benzene. Loss of RB yielded
      a unique proliferative response to this agent, which was distinct from both
      regenerative stresses and genotoxic carcinogens. Long-term exposure to 1,4-Bis-[2
      (3,5-dichloropyridyloxy)] benzene yielded profound tumor development in RB
      deficient livers that was principally absent in RB-sufficient tissue. These data
      demonstrate the context specificity of RB and the key role RB plays in the
      suppression of hepatocellular carcinoma driven by xenobiotic stress. 

PMID- 24726647
TI  - Activation of Notch1 promotes development of human CD8(+) single positive T cells
      in humanized mice.
AB  - Notch1 mutations are found in more than 50% of human T cell acute lymphoblastic
      leukemia (T-ALL) cells. However, the functions of Notch1 for human T cell
      development and leukemogenesis are not well understood. To examine the role of
      Notch1, human hematopoietic stem cells (HSCs), which had been transduced with a
      constitutively active form of Notch1 (ICN1), were transplanted into severely
      immunodeficient NOD/Shi-scid-IL2rgamma(null) (NOG) mice. We found that the great
      majority of the ICN1-expressing hematopoietic cells in the bone marrow expressed
      surface markers for T cells, such as CD3, CD4, and CD8, and that this T cell
      development was independent of the thymus. Accordingly, phenotypically mature
      CD8(+) single positive (SP) T cells were observed in the spleen. Furthermore, T
      ALL developed in one NOG recipient mouse out of 26 that had been secondary
      transferred with the T cells developed in the first NOG mice. These results
      indicate that Notch1 signaling in HSCs promotes CD8(+) SP T cell development, and
      that T cell leukemogenesis may require additional oncogenic factors other than
      Notch1 activation. 

PMID- 24726646
TI  - Neutrophil dependence of vascular remodeling after Mycoplasma infection of mouse
      airways.
AB  - Vascular remodeling is a feature of sustained inflammation in which capillaries
      enlarge and acquire the phenotype of venules specialized for plasma leakage and
      leukocyte recruitment. We sought to determine whether neutrophils are required
      for vascular remodeling in the respiratory tract by using Mycoplasma pulmonis
      infection as a model of sustained inflammation in mice. The time course of
      vascular remodeling coincided with the influx of neutrophils during the first few
      days after infection and peaked at day 5. Depletion of neutrophils with antibody
      RB6-8C5 or 1A8 reduced neutrophil influx and vascular remodeling after infection
      by about 90%. Similarly, vascular remodeling after infection was suppressed in
      Cxcr2(-/-) mice, in which neutrophils adhered to the endothelium of venules but
      did not extravasate into the tissue. Expression of the venular adhesion molecule
      P-selectin increased in endothelial cells from day 1 to day 3 after infection, as
      did expression of the Cxcr2-receptor ligands Cxcl1 and Cxcl2. Tumor necrosis
      factor alpha (TNFalpha) expression increased more than sixfold in the trachea of
      wild-type and Cxcr2(-/-) mice, but intratracheal administration of TNFalpha did
      not induce vascular remodeling similar to that seen in infection. We conclude
      that neutrophil influx is required for remodeling of capillaries into venules in
      the airways of mice with Mycoplasma infection and that TNFalpha signaling is
      necessary but not sufficient for vascular remodeling.

PMID- 24726648
TI  - Integrin alphav in the mechanical response of osteoblast lineage cells.
AB  - Although osteoblast lineage cells, especially osteocytes, are thought to be a
      primary mechanosensory cell in bone, the identity of the mechano-receptor and
      downstream mechano-signaling pathways remain largely unknown. Here we show using
      osteoblastic cell model of mechanical stimulation with fluid shear stress that in
      the absence of integrin alphav, phosphorylation of the Src substrate p130Cas and
      JNK was impaired, culminating in an inhibition of nuclear translocation of
      YAP/TAZ and subsequent transcriptional activation of target genes. Targeted
      deletion of the integrin alphav in osteoblast lineage cells results in an
      attenuated response to mechanical loading in terms of Sost gene expression,
      indicative of a role for integrin alphav in mechanoreception in vivo. Thus,
      integrin alphav may be integral to a mechanosensing machinery in osteoblastic
      cells and involved in activation of a Src-JNK-YAP/TAZ pathway in response to
      mechanical stimulation. 

PMID- 24726649
TI  - Multiple sclerosis: Benefits of q-space imaging in evaluation of normal-appearing
      and periplaque white matter.
AB  - INTRODUCTION: Diffusion tensor imaging (DTI) reveals white matter pathology in
      patients with multiple sclerosis (MS). A recent non-Gaussian diffusion imaging
      technique, q-space imaging (QSI), may provide several advantages over
      conventional MRI techniques in regard to in vivo evaluation of the disease
      process in patients with MS. The purpose of this study is to investigate the use
      of root mean square displacement (RMSD) derived from QSI data to characterize
      plaques, periplaque white matter (PWM), and normal-appearing white matter (NAWM)
      in patients with MS. METHODS: We generated apparent diffusion coefficient (ADC)
      and fractional anisotropy (FA) maps by using conventional DTI data from 21 MS
      patients; we generated RMSD maps by using QSI data from these patients. We used
      the Steel-Dwass test to compare the diffusion metrics of regions of interest in
      plaques, PWM, and NAWM. RESULTS: ADC differed (P<0.05) between plaques and PWM
      and between plaques and NAWM. FA differed (P<0.05) between plaques and NAWM. RMSD
      differed (P<0.05) between plaques and PWM, plaques and NAWM, and PWM and NAWM.
      CONCLUSION: RMSD values from QSI may reflect microstructural changes and white
      matter damage in patients with MS with higher sensitivity than do conventional
      ADC and FA values.

PMID- 24726650
TI  - Hypereosinophilic syndrome.
AB  - OBJECTIVE: To summarize the identified molecular and cellular mechanisms relevant
      to clinicians evaluating patients with hypereosinophilic syndrome (HES). DATA
      SOURCES: Review of relevant peer-reviewed literature. STUDY SELECTIONS: Studies
      on the pathogenesis of HES in relation to consensus definitions, disease
      classification, mechanisms of disease, and diagnosis and treatment are included.
      RESULTS: Changes to the definition of HES have been proposed based on recent
      studies identifying specific cellular and molecular disease phenotypes.
      Identification of specific mechanisms of disease may have clinical and
      therapeutic significance. Despite recent advances, in most cases the molecular
      pathogenesis of HES remains unknown. CONCLUSION: Identification of specific HES
      disease mechanisms empowers the practicing clinician to offer specific mechanism
      based treatment options to patients with HES in their clinical practice.

PMID- 24726651
TI  - Changes in cat specific IgE and IgG antibodies with decreased cat exposure.
AB  - BACKGROUND: Current understanding of the effects of reducing exposure to cat
      allergens is limited. It has also become clear that there are different forms of
      immune response to cat allergens. OBJECTIVE: To investigate changes in skin tests
      and cat specific IgG and IgE antibodies when students from a home with a cat move
      to a college dormitory. METHODS: Ninety-seven college students participated in a
      prospective study that consisted of allergy skin prick testing and serum
      measurement of IgE and IgG antibodies to cat at the beginning and end of one
      academic year in college. A subgroup returned for follow-up at the end of 2
      years. RESULTS: Among 97 students, 33% had IgG antibodies to Fel d 1 but no
      evidence of sensitization, 25% had positive skin test results and/or serum IgE
      antibodies, and 42% had negative skin test results and no detectable serum
      antibodies. Among the non-cat sensitized students with IgG antibodies, the titers
      decreased during 8 months (P = .002). Titers of IgG4 to Fel d 1 also decreased (P
      < .001). Among the sensitized students, no change in IgE antibodies to cat
      occurred in 8 months (P = .20), whereas Fel d 1 specific IgG antibodies decreased
      (P < .001). Thus, ratios of IgG to IgE decreased highly significantly (P = .007).
      Among the students with negative skin test results who returned for follow-up (n
      = 56), none developed positive skin test results or serum IgE antibodies.
      CONCLUSION: Under conditions of marked decrease in exposure, no participants
      developed new-onset sensitization. Among the individuals sensitized at study
      entry, there were major decreases in the ratio of IgG to IgE.

PMID- 24726652
TI  - Microbial transglutaminase: a new and emerging occupational allergen.

PMID- 24726653
TI  - Is echogenicity a viable metric for evaluating tendon properties in vivo?
AB  - Material properties of tissue in vivo present an opportunity for clinical
      analysis of healing progression and pathologies as well as provide an excellent
      research tool yielding quantified data for longitudinal and cross population
      studies. Echogenicity is a material's ability to reflect sound and, using
      ultrasound, it has been shown to increase with tendon tension in vitro, though
      this non-invasive measurement technique for determining mechanical properties has
      not been tested in vivo. The aim of this study was to establish if echogenicity,
      seen by the increase in image brightness, could be correlated to stress within a
      tissue. 18 Achilles tendons were imaged in the sagittal and transverse planes
      while producing a series of isometric contractions starting from rest and
      producing the torque equivalent of 0.5, 1.0, 1.5, and 2.0* body weights. Manual
      tracing identified the tendon in each of the images. The cross-sectional area
      determined from the transverse plane images in conjunction with the tendon force
      yielded the tendon stress. The echogenicity of the tendon was determined from the
      mean brightness change from rest to each of the contraction cases, measured from
      the sagittal plane images. A weak correlation existed between the echogenicity
      and stress (R=0.25) but it was found that there was no significant change in
      axial area during contraction (p=0.683) establishing the tendon as
      incompressible. Echogenicity proved to be non-functional for measuring the
      mechanical properties of the Achilles tendon due to the additional factors
      included with in vivo testing e.g. tendon twist and multi-axial loading. 

PMID- 24726654
TI  - Optimal cycling time trial position models: aerodynamics versus power output and
      metabolic energy.
AB  - The aerodynamic drag of a cyclist in time trial (TT) position is strongly
      influenced by the torso angle. While decreasing the torso angle reduces the drag,
      it limits the physiological functioning of the cyclist. Therefore the aims of
      this study were to predict the optimal TT cycling position as function of the
      cycling speed and to determine at which speed the aerodynamic power losses start
      to dominate. Two models were developed to determine the optimal torso angle: a
      'Metabolic Energy Model' and a 'Power Output Model'. The Metabolic Energy Model
      minimised the required cycling energy expenditure, while the Power Output Model
      maximised the cyclists' power output. The input parameters were experimentally
      collected from 19 TT cyclists at different torso angle positions (0-24 degrees ).
      The results showed that for both models, the optimal torso angle depends strongly
      on the cycling speed, with decreasing torso angles at increasing speeds. The
      aerodynamic losses outweigh the power losses at cycling speeds above 46km/h.
      However, a fully horizontal torso is not optimal. For speeds below 30km/h, it is
      beneficial to ride in a more upright TT position. The two model outputs were not
      completely similar, due to the different model approaches. The Metabolic Energy
      Model could be applied for endurance events, while the Power Output Model is more
      suitable in sprinting or in variable conditions (wind, undulating course, etc.).
      It is suggested that despite some limitations, the models give valuable
      information about improving the cycling performance by optimising the TT cycling
      position. 

PMID- 24726655
TI  - Defined serum-free media for in vitro expansion of adipose-derived mesenchymal
      stem cells.
AB  - BACKGROUND: There is a growing interest in mesenchymal stem cells (MSCs) because
      they are regarded as good candidates for cell therapy. Adipose tissue represents
      an easily accessible source to derive mesenchymal stem cells (Ad-MSCs) non
      invasively in large numbers. The aim of this study was to evaluate a defined
      serum-free medium for in vitro expansion of MSCs as a prerequisite for their
      clinical use. METHODS: Adipose tissue was isolated from healthy donors. Cells
      were isolated and expanded for five passages in serum-free medium (Mesencult-XF)
      and Dulbecco's modified Eagle's medium supplemented with 10% fetal bovine serum
      (DMEM-FBS). MSC morphology, marker expression, viability, population doubling
      time and differentiation potential toward osteogenic and adipogenic lineages were
      evaluated. Bone marrow MSCs were included as controls. RESULTS: Ad-MSCs cultured
      in Mesencult-XF had shorter population doubling time (33.3 +/- 13.7 h) compared
      with those cultured in DMEM-FBS (54.3 +/- 41.0 h, P < 0.05). Ad-MSCs cultured in
      Mesencult-XF displayed a stable morphology and surface marker expression and a
      higher differentiation potential in comparison to Ad-MSCs cultured in DMEM-FBS.
      CONCLUSIONS: The defined serum-free and xeno-free Mesencult-XF media appear to be
      a good choice for Ad-MSCs, but it is not as good in supporting culture of bone
      marrow MSCs when the cells are to be used for clinical purposes.

PMID- 24726656
TI  - Age influence on stromal vascular fraction cell yield obtained from human
      lipoaspirates.
AB  - BACKGROUND AIMS: The adipose stromal vascular fraction (SVF) is a heterogeneous
      population of mononuclear cells that includes approximately 1-10% mesenchymal
      stromal cells. These SVF cells can be freshly obtained from human lipo-aspirates
      and represent and ideal candidate for regenerative medicine applications. In the
      present study, we analyzed the SVF yield as a function of the patient's age.
      METHODS: Adipose tissue samples from 52 informed subjects (all women) were
      processed by means of an innovative point-of-care technology for SVF isolation
      (GID platform). After enzymatic dissociation of adipose tissue and SVF pellet
      resuspension, we measured the concentration of mononucleated cells as well as
      other cell quality analyses on the cell suspension obtained. We then calculated
      the cell yield as total nucleated cells per milliliter of dry adipose processed.
      RESULTS: The mean SVF yield obtained was 7.19 * 10(5) +/- 2.11 * 10(5) total
      nucleated cells per milliliter of adipose tissue. Our results show that there is
      a clear statistically significant decline in SVF cell yield with increasing age.
      CONCLUSIONS: Because all samples were obtained from the same donor area and the
      isolation technique used was the same in all cases, we conclude that the SVF cell
      yield in women is affected by patient age. Specific age-related factors should be
      analyzed in the future to explain these results.

PMID- 24726657
TI  - Efficient manufacturing of therapeutic mesenchymal stromal cells with the use of
      the Quantum Cell Expansion System.
AB  - BACKGROUND: The use of bone marrow-derived mesenchymal stromal cells (MSCs) as a
      cellular therapy for various diseases, such as graft-versus-host disease,
      diabetes, ischemic cardiomyopathy and Crohn's disease, has produced promising
      results in early-phase clinical trials. However, for widespread application and
      use in later phase studies, manufacture of these cells must be cost-effective,
      safe and reproducible. Current methods of manufacturing in flasks or cell
      factories are labor-intensive, involve a large number of open procedures and
      require prolonged culture times. METHODS: We evaluated the Quantum Cell Expansion
      System for the expansion of large numbers of MSCs from unprocessed bone marrow in
      a functionally closed system and compared the results with a flask-based method
      currently in clinical trials. RESULTS: After only two passages, we were able to
      expand a mean of 6.6 * 10(8) MSCs from 25 mL of bone marrow reproducibly. The
      mean expansion time was 21 days, and cells obtained were able to differentiate
      into all three lineages: chondrocytes, osteoblasts and adipocytes. The Quantum
      was able to generate the target cell number of 2.0 * 10(8) cells in an average of
      9 fewer days and in half the number of passages required during flask-based
      expansion. We estimated that the Quantum would involve 133 open procedures versus
      54,400 in flasks when manufacturing for a clinical trial. Quantum-expanded MSCs
      infused into an ischemic stroke rat model were therapeutically active.
      CONCLUSIONS: The Quantum is a novel method of generating high numbers of MSCs in
      less time and at lower passages when compared with flasks. In the Quantum, the
      risk of contamination is substantially reduced because of the substantial
      decrease in open procedures.

PMID- 24726658
TI  - Low oxygen atmosphere facilitates proliferation and maintains undifferentiated
      state of umbilical cord mesenchymal stem cells in an hypoxia inducible factor
      dependent manner.
AB  - BACKGROUND AIMS: As we approach the era of mesenchymal stem cell (MSC)
      application in the medical clinic, the standarization of their culture conditions
      are of the particular importance. We re-evaluated the influences of oxygens
      concentration on proliferation, stemness and differentiation of human umbilical
      cord Wharton Jelly-derived MSCs (WJ-MSCs). METHODS: Primary cultures growing in
      21% oxygen were either transferred into 5% O2 or continued to grow under standard
      21% oxygen conditions. Cell expansion was estimated by WST1/enzyme-linked
      immunosorbent assay or cell counting. After 2 or 4 weeks of culture, cell
      phenotypes were evaluated using microscopic, immunocytochemical, fluorescence
      activated cell-sorting and molecular methods. Genes and proteins typical of
      mesenchymal cells, committed neural cells or more primitive stem/progenitors
      (Oct4A, Nanog, Rex1, Sox2) and hypoxia inducible factor (HIF)-1alpha-3alpha were
      evaluated. RESULTS: Lowering O2 concentration from 21% to the physiologically
      relevant 5% level substantially affected cell characteristics, with induction of
      stemness-related-transcription-factor and stimulation of cell proliferative
      capacity, with increased colony-forming unit fibroblasts (CFU-F) centers exerting
      OCT4A, NANOG and HIF-1alpha and HIF-2alpha immunoreactivity. Moreover, the
      spontaneous and time-dependent ability of WJ-MSCs to differentiate into neural
      lineage under 21% O2 culture was blocked in the reduced oxygen condition.
      Importantly, treatment with trichostatin A (TSA, a histone deacetylase inhibitor)
      suppressed HIF-1alpha and HIF-2alpha expression, in addition to blockading the
      cellular effects of reduced oxygen concentration. CONCLUSIONS: A physiologically
      relevant microenvironment of 5% O2 rejuvenates WJ-MSC culture toward less
      differentiated, more primitive and faster-growing phenotypes with involvement of
      HIF-1alpha and HIF-2alpha-mediated and TSA-sensitive chromatin modification
      mechanisms. These observations add to the understanding of MSC responses to
      defined culture conditions, which is the most critical issue for adult stem cells
      translational applications.

PMID- 24726659
TI  - Determining heavy metals in spent compact fluorescent lamps (CFLs) and their
      waste management challenges: some strategies for improving current conditions.
AB  - From environmental viewpoint, the most important advantage of compact fluorescent
      lamps (CFLs) is reduction of green house gas emissions. But their significant
      disadvantage is disposal of spent lamps because of containing a few milligrams of
      toxic metals, especially mercury and lead. For a successful implementation of any
      waste management plan, availability of sufficient and accurate information on
      quantities and compositions of the generated waste and current management
      conditions is a fundamental prerequisite. In this study, CFLs were selected among
      20 different brands in Iran. Content of heavy metals including mercury, lead,
      nickel, arsenic and chromium was determined by inductive coupled plasma (ICP).
      Two cities, Tehran and Tabriz, were selected for assessing the current waste
      management condition of CFLs. The study found that waste generation amount of
      CFLs in the country was about 159.80, 183.82 and 153.75 million per year in 2010,
      2011 and 2012, respectively. Waste generation rate of CFLs in Iran was determined
      to be 2.05 per person in 2012. The average amount of mercury, lead, nickel,
      arsenic and chromium was 0.417, 2.33, 0.064, 0.056 and 0.012 mg per lamp,
      respectively. Currently, waste of CFLs is disposed by municipal waste stream in
      waste landfills. For improving the current conditions, we propose by considering
      the successful experience of extended producer responsibility (EPR) in other
      electronic waste management. The EPR program with advanced recycling fee (ARF) is
      implemented for collecting and then recycling CFLs. For encouraging consumers to
      take the spent CFLs back at the end of the products' useful life, a proportion of
      ARF (for example, 50%) can be refunded. On the other hand, the government and
      Environmental Protection Agency should support and encourage recycling companies
      of CFLs both technically and financially in the first place.

PMID- 24726660
TI  - Ultrafine particle emission of waste incinerators and comparison to the exposure
      of urban citizens.
AB  - On the basis of the growing interest on the impact of airborne particles on human
      exposure as well as the strong debate in Western countries on the emissions of
      waste incinerators, this work reviewed existing literature to: (i) show the
      emission factors of ultrafine particles (particles with a diameter less than 100
      nm) of waste incinerators; and (ii) assess the contribution of waste incinerators
      in terms of ultrafine particles to exposure and dose of people living in the
      surrounding areas of the plants in order to estimate eventual risks. The review
      identified only a limited number of studies measuring ultrafine particle
      emissions, and in general they report low particle number concentrations at the
      stack (the median value was equal to 5.5*10(3) part cm(-3)), in most cases higher
      than the outdoor background value. The lowest emissions were achieved by
      utilization of the bag-house filter which has an overall number-based filtration
      efficiency higher than 99%. Referring to reference case, the corresponding
      emission factor is equal to 9.1*10(12) part min(-1), that is lower than one
      single high-duty vehicle. Since the higher particle number concentrations found
      in the most contributing microenvironments to the exposure (indoor home,
      transportation, urban outdoor), the contribution of the waste incinerators to the
      daily dose can be considered as negligible.

PMID- 24726662
TI  - Towards a method for determining age ranges from faces of juveniles on
      photographs.
AB  - The steady increase in the distribution of juvenile pornographic material in
      recent years strongly required valid methods for estimating the age of the
      victims. At the present in fact forensic experts still commonly use the
      assessment of sexual characteristics by Tanner staging, although they have proven
      to be too subjective and deceiving for age estimation. The objective of this
      study, inspired by a previous EU project involving Italy, Germany and Lithuania,
      is to verify the applicability of certain anthropometric indices of faces in
      order to determine age and to create a database of facial measurements on a
      population of children in order to improve face ageing techniques. In this study,
      1924 standardized facial images in frontal view and 1921 in lateral view of
      individuals from 7 age groups (3-5 years, 6-8 years, 9-11 years, 12-14 years, 15
      17 years, 18-20 years, 21-24 years) underwent metric analysis. Individuals were
      all of Caucasoid ancestry and Italian nationality. Eighteen anthropometric
      indices in the frontal view and five in the lateral view were then calculated
      from the obtained measurements. Indices showing a correlation with age were ch
      ch/ex-ex, ch-ch/pu-pu, en-en/ch-ch and se-sto/ex-ex in the frontal view, se
      prn/se-sn, se-prn/se-sto and se-sn/se-sto in the lateral view. All the indices
      increased with age except for en-en/ch-ch, without relevant differences between
      males and females. These results provide an interesting starting point not only
      for placing a photographed face in an age range but also for refining the
      techniques of face ageing and personal identification. 

PMID- 24726663
TI  - Fungal infection in patients with end-stage liver disease: low frequency or low
      index of suspicion.
AB  - BACKGROUND: End-stage liver disease (ESLD) is associated with dysregulation of
      the immune system and increased susceptibility to infections. Although invasive
      fungal infection (IFI) is a growing public health problem, studies of IFI in ESLD
      are lacking. The aims of this study were to screen for IFI in ESLD and to assess
      risk factors and serum interleukin 17 (IL-17) as a marker of the cellular immune
      response. METHODS: Both blood and ascitic fluid samples were collected from 46
      patients with ESLD for fungal culture and PCR. Serum IL-17 levels were
      determined. RESULTS: Seven patients had isolated IFI (four had spontaneous fungal
      peritonitis, two had fungemia, and one had a disseminated fungal infection) and
      five cases had combined fungal and bacterial infections. Spontaneous fungal
      peritonitis was attributed to Candida species, while fungemia was caused by
      Aspergillus species. Patients with IFI had higher serum IL-17 levels and
      increased mortality compared to patients without IFI. A history of antibiotic use
      (p = 0.002), higher model for end-stage liver disease (MELD) scores (p = 0.04),
      and hepatorenal syndrome (p = 0.006) were risk factors for IFI. CONCLUSIONS:
      Patients with ESLD had a low frequency of IFI; however, in patients with these
      infections, delayed diagnosis and treatment may contribute to a high fatality
      rate. Thus, clinicians should have a high index of suspicion for this unusual but
      lethal entity, as prompt detection and appropriate treatment can improve the
      outcome.

PMID- 24726664
TI  - A retrospective analysis of carbapenem-resistant Acinetobacter baumannii-mediated
      nosocomial pneumonia and the in vitro therapeutic benefit of
      cefoperazone/sulbactam.
AB  - BACKGROUND: Acinetobacter baumannii has been reported increasingly as a
      significant causative organism of various nosocomial infections, including
      hospital-acquired pneumonia (HAP). The aim of this study was to investigate the
      clinical characteristics of HAP induced by carbapenem-resistant A. baumannii
      (CRAB) in elderly patients and the in vitro antimicrobial effects of
      cefoperazone/sulbactam combination therapy. METHODS: Seventy-one elderly patients
      in the geriatric ward of the General Hospital of the People's Liberation Army
      (PLAGH) with CRAB-induced HAP were analyzed retrospectively. The checkerboard
      method was used to determine the in vitro drug sensitivity of 60 CRAB strains to
      antimicrobial combinations (cefoperazone/sulbactam with meropenem, minocycline,
      or levofloxacin). The occurrence of carbapenemase genes was detected by PCR.
      RESULTS: CRAB-induced HAP occurred mostly in patients with underlying diseases.
      Prior to onset, most patients had received antimicrobial therapies including
      broad-spectrum beta-lactams, invasive mechanical ventilation, and
      catheterization. The 30-day survival rate was 95.1% in patients using
      cefoperazone/sulbactam, with or without combination with antimicrobial drugs, and
      73.3% in patients not using cefoperazone/sulbactam (p<0.05). When
      cefoperazone/sulbactam was used in combination with minocycline, levofloxacin,
      and meropenem, minimum inhibitory concentrations MIC50 and MIC90 were reduced for
      each drug. The genes OXA-23 and OXA-51 were amplified in 96.7% of the strains,
      but the genes OXA-24, OXA-58, SIM, VIM, and IMP were not amplified. CONCLUSIONS:
      CRAB-induced HAP occurred mostly in patients with anemia or decreased levels of
      serum albumin, but with elevated levels of C-reactive protein and creatinine.
      Cefoperazone/sulbactam in combination with minocycline, meropenem, and
      levofloxacin had a synergistic and additive in vitro bacteriostatic action on
      CRAB.

PMID- 24726665
TI  - Galanin promotes neuronal differentiation from neural progenitor cells in vitro
      and contributes to the generation of new olfactory neurons in the adult mouse
      brain.
AB  - Galanin is a pleiotropic neuropeptide widely expressed in the nervous system. It
      plays a role in many diverse physiological functions - including nociception,
      cognition and metabolism regulation - and acts as neurotrophic/neuroprotective
      factor for several neuronal populations. In this article we sought to determine
      the role of galanin on neural stem cell function and its contribution to the
      plasticity of the nervous system. Here we show that galanin and its receptors are
      expressed in neural progenitor cells (NPCs) isolated from the developing
      striatum. Stimulation with galanin results in upregulation of Bcl-Xl, Bcl-2, Mash
      1 and Olig-2 that are part of well known pro-survival/pro-neuronal signalling
      pathways. Accordingly, treatment with galanin increases the number of neurons
      upon differentiation from these progenitors. We then show that these effects are
      recapitulated in NPCs isolated from the adult subventricular zone (SVZ), where
      galanin increases the total number of neurons and the number of newly-generated
      neurons upon differentiation in vitro. The significance of these findings is
      highlighted in the adult brain where loss of galanin leads to a marked decrease
      in the rate of adult SVZ neurogenesis and a reduction in the number of newly
      generated cells in the olfactory bulb. Interestingly, Gal-KO mice display normal
      performances in simple tasks of olfactory detection and discrimination, which
      points to the existence of a certain degree of redundancy in SVZ neurogenesis.
      Our findings establish the role of galanin as a modulator of neural stem cell
      function and support the importance of galanin for brain plasticity and repair. 

PMID- 24726666
TI  - Sex differences in behavioral outcome following neonatal hypoxia ischemia:
      Insights from a clinical meta-analysis and a rodent model of induced hypoxic
      ischemic injury.

PMID- 24726661
TI  - Sex differences in stress-related psychiatric disorders: neurobiological
      perspectives.
AB  - Stress is associated with the onset and severity of several psychiatric disorders
      that occur more frequently in women than men, including posttraumatic stress
      disorder (PTSD) and depression. Patients with these disorders present with
      dysregulation of several stress response systems, including the neuroendocrine
      response to stress, corticolimbic responses to negatively valenced stimuli, and
      hyperarousal. Thus, sex differences within their underlying circuitry may explain
      sex biases in disease prevalence. This review describes clinical studies that
      identify sex differences within the activity of these circuits, as well as
      preclinical studies that demonstrate cellular and molecular sex differences in
      stress responses systems. These studies reveal sex differences from the molecular
      to the systems level that increase endocrine, emotional, and arousal responses to
      stress in females. Exploring these sex differences is critical because this
      research can reveal the neurobiological underpinnings of vulnerability to stress
      related psychiatric disorders and guide the development of novel
      pharmacotherapies. 

PMID- 24726667
TI  - [Brain imaging in early onset anorexia].
AB  - Structural and functional brain alterations in the structures involved in taste
      processing, emotions regulation and the reward system have been described in
      anorexia nervosa. The neurodevelopmental origin of this disorder has been
      recently discussed. In this article, brain-imaging data in early onset anorexia
      nervosa will be recalled and the relationship between clinical symptoms, normal
      brain maturation and brain imaging data in adolescents and adults will be
      discussed. 

PMID- 24726668
TI  - [Severe nutritional deficiencies in young infants with inappropriate plant milk
      consumption].
AB  - Over the past few years, we have observed increasing consumption of inappropriate
      plant milks as an alternative to infant milk formula. Some families believe that
      foods labeled as natural are the most healthy and an appropriate nutritional
      choice. However, their composition does not respect European recommendations.
      They are always hypocaloric and protein, vitamin, and mineral concentrations are
      inadequate. The aim of this study was to report severe nutritional complications
      after inappropriate plant milk consumption. Between 2008 and 2011, we studied
      severe nutritional deficiencies caused by consumption of plant milks bought in
      health food stores or online shops. Infants were identified in our centers and
      examined through medical history, physical examination, and laboratory testing.
      Nine cases of infants aged from 4 to 14 months were observed. In all cases, these
      milks were used as an alternative to milk formulas for supposed cow's milk
      allergy. At diagnosis, four patients were aged 6 months or less. They had
      received plant milk exclusively for 1-3 months. The beverages consumed were rice,
      soya, almond and sweet chestnut milks. In three cases, infants presented severe
      protein-calorie malnutrition with substantial hypoalbuminemia (<20 g/L) and
      diffuse edema. In the other cases, the nutritional disorders were revealed by a
      refractory status epilepticus related to severe hypocalcemia (one case), growth
      arrest of both height and weight secondary to insufficient caloric intake (five
      cases), and severe cutaneous involvement (one case). Five children had severe
      iron deficiency anemia (<70 g/L), three children had a very low 25-hydroxy
      vitamin D level (nutritional rickets), and two had severe hyponatremia (<130
      mmoL/L). Milk alternative beverages expose infants to severe nutritional
      deficiencies. Serious complications can occur. Early, exclusive, and extended use
      is riskier. These diseases are preventable, and parental education should be
      provided. Statutory measures forbidding their use in young infants should be
      organized to slow down the progress of this social trend.

PMID- 24726669
TI  - [Acute cough in infants: impact on families and pharmacists of contraindications
      of the Agence nationale de securite du medicament et des produits de sante
      (ANSM)].
AB  - CONTEXT AND OBJECTIVE: Although commonplace and usually not serious, acute cough
      in the context of upper respiratory tract infection is a frequent reason for
      consultation and generates significant parental anxiety. Parents often request
      active drug intervention. Following the contraindications in infants of
      mucolytics, Helicidine((r)), antihistamines, and terpene-based suppositories,
      issued between 2010 and 2011 by the Agence nationale de securite du medicament et
      des produits de sante (ANSM), we wished to assess whether these contraindications
      were known by parents and applied in pharmacies. MATERIALS AND METHODS: An
      assessment of compliance with these contraindications was made by a double
      declarative prospective observational study in Nice, first with 29 pharmacists
      and pharmacy technicians (4-25 August 2012) and then with 289 parents of infants
      (December 2011 to April 2012). RESULTS: The rate of noncompliance with
      contraindications was 23.8 % for parents and 34.5 % of pharmacists and pharmacy
      technicians. Consumption of cough medicines was inversely correlated to the
      ability to perform a correct nasal wash (OR=2.3). Only 21 % of parents used nasal
      wash properly. Full-time work was a risk factor for noncompliance with
      contraindications (OR=1.91). CONCLUSION: ANSM contraindications still have a
      limited impact on pharmacists and families. Therefore, efforts must be pursued to
      stop delivering cough medicines for infants. The information and educational
      campaigns should also involve parents and help to improve nasal wash use.

PMID- 24726670
TI  - [Hypothalamic hamartoma revealing gelastic seizures].

PMID- 24726672
TI  - [Implementation of a specific premedication protocol for tracheal intubation in
      the delivery room. Practice in two level-III hospitals].
AB  - Tracheal intubation in neonates is a painful procedure performed daily in the
      delivery room despite the widespread development of noninvasive ventilation.
      Specific analgesia is not commonly performed. The objective of this observational
      study was to compare practices between two level-III centers: one with a specific
      protocol for premedication before tracheal intubation of newborns in the delivery
      room, the other without. RESULTS: One hundred and fifteen neonates were intubated
      in the delivery room and included over a 4-month period: 25% of them received
      specific premedication before intubation, exclusively in the center with the
      protocol. None of the extreme premature neonates (age<=28 gestational weeks)
      received analgosedation before the procedure. Nalbuphine, midazolam, and
      sufentanil were mainly used, via the intravenous or intrarectal route. Infants
      receiving a premedication were significantly heavier and had a greater
      gestational age than the others (1500 g [range, 1180-2260 g] vs. 1170 [range, 860
      1680 g] P=0.003, and 31 GW [range, 29-34 GW] vs. 29 [range, 27-32 GW] P=0.014,
      respectively). Most pediatricians (85-100%) favored a specific protocol for
      sedation before tracheal intubation. Implementation of a specific protocol allows
      specific analgesia to be implemented for newborns undergoing tracheal intubation.
      Further studies should be conducted to determine the best strategies for pain
      management during tracheal intubation of neonates, especially in the delivery
      room.

PMID- 24726673
TI  - Easy performance of 6-color confocal immunofluorescence with 4-laser line
      microscopes.
AB  - Confocal laser scanning microscopy is an advanced technique for imaging tissue
      samples in vitro and in vivo at high optical resolution. The development of new
      fluorochrome variants do not only make it possible to perform multicolor flow
      cytometry of single cells, but in combination with high resolution laser scanning
      systems also to investigate the distribution of cells in lymphoid tissues by
      confocal immunofluorescence analyses, thus allowing the distinction of various
      cell populations directly in the tissue. Here, we provide a protocol for the
      visualization of at least six differently fluorochrome-labeled antibodies at the
      same time using a conventional confocal laser scanning microscope with four laser
      lines (405 nm, 488 nm, 555 nm, and 639 nm laser wavelength) in both murine and
      human tissue samples. We further demonstrate that compensation correction
      algorithms are not necessary to reduce spillover of fluorochromes into other
      channels when the used fluorochromes are combined according to their specific
      emission bands and the varying Stokes shift for co-excited fluorochromes with the
      same laser line.

PMID- 24726674
TI  - The characteristics, management, and aftercare of patients with suicide attempts
      who attended the emergency department of a general hospital in northern Taiwan.
AB  - BACKGROUND: Suicide is a serious public health problem worldwide. The emergency
      department (ED) is often the first place of contact with medical and mental
      health care for suicidal patients. This study aimed to determine the
      characteristics, management, and aftercare of patients who attempted suicide and
      then were taken to the ED of a general hospital in Taipei, Taiwan. METHODS: Our
      study was a cross-sectional retrospective study that consecutively recruited
      patients with suicide attempts attended to the ED of a general hospital from June
      2004 to May 2005. The patients' medical information and records pertaining to
      their emergency visit were subsequently reviewed. RESULTS: Overall, 481 persons
      were recruited into our study. The male:female ratio of total surviving
      attempters was approximately 1:4 and the average age was 33.6 [standard deviation
      (SD) 12.3] years. The most frequently observed general characteristics from which
      participants suffered were mental illness (73.1%) and interpersonal problems
      (76.1%). Nearly all patients (91.7%) received ED on-site psychosocial assessments
      from social workers (SWs) and psychiatrists in 84.2% and 53.4% of cases,
      respectively. Less than half of patients (45.1%) were referred to psychiatric
      outpatient aftercare, and only 26.1% contacted the psychiatric outpatient clinics
      after discharge from the ED. The stated reasons for psychiatric outpatient
      referral were associated with interpersonal problems, current psychiatric
      illness, the ED on-site psychiatrist consultation, and admission to medical,
      surgical, or psychiatric wards. However, individuals with interpersonal problems,
      previous psychiatric intervention, and ED on-site psychiatrist consultation were
      significantly more likely to attend outpatient psychiatric aftercare. CONCLUSION:
      Individuals who harmed themselves had a high rate of psychiatric morbidity and
      interpersonal problems. However, their adherence to psychiatric outpatient
      aftercare was low. Improved identification of the needs of patients with suicidal
      tendencies who did not attend outpatient services will have implications for
      future services provided to this patient population, and will better enable
      medical personnel to most effectively assist in suicide attempt interventions.

PMID- 24726675
TI  - Unusual computed tomography features of ruptured sarcomatous hepatocellular
      carcinoma.
AB  - Sarcomatous change in hepatocellular carcinoma (HCC) is an uncommon histologic
      variant of HCC, characterized by the proliferation of spindle cells or bizarre
      giant cells. Poor outcome has been reported in most cases after diagnosis. Here,
      we report the first case of a sarcomatous HCC with complete central necrosis and
      rupture of the liver capsule. The patient received target therapy with sorafenib,
      but died of progressive intra-abdominal carcinomatosis 3 months after treatment.
      We reviewed the published reports of 13 patients with sarcomatous HCC that
      included computed tomography features and found that our patient was the only one
      to have received sorafenib. It appears that this patient's life span was not
      significantly prolonged with the use of sorafenib. 

PMID- 24726676
TI  - Application of an ultrasound-guided low-approach insertion technique in three
      types of totally implantable access port.
AB  - BACKGROUND: Totally implantable access ports (TIAPs) are alternatives to central
      venous catheters for patients requiring chemotherapy. Since January 2003, we have
      used a central approach two-point incision technique to insert TIAPs. Following
      advances in ultrasound technique and clinical experience for tunneled dialysis
      catheter placement, we modified the central approach to a low-approach technique.
      METHODS: From January 2009 to June 2010, patients consulted for TIAP insertion in
      our department were enrolled in our study. Different brands and materials of
      central venous catheters of TIAPs were inserted by the low-approach two-point
      incision technique (Phase I) or the low-approach one-point incision technique
      (Phase II). The insertion time, failure rate, procedural and late complications,
      degree of satisfaction, and cosmetic scores were recorded. RESULTS: Ninety-seven
      patients and 107 patients were implanted via the two-point and one-point low
      approach techniques, respectively, with different kinds of TIAP. No matter which
      type of TIAP was used, the success rate in both phases was 100% without
      procedural complications using the low-approach technique. The average time for
      device insertion was 30 minutes for the two-point incision technique used during
      Phase I and 26-28 minutes for the one-point incision technique used during Phase
      II. Satisfaction and cosmetic scores were high. CONCLUSION: Our study highlights
      a revised technique for placement of TIAP systems of differing types of material
      or size. Not only was the curvature of the device catheter smooth, but patients
      were satisfied with the cosmetic appearance.

PMID- 24726677
TI  - Sesamin reduces acute hepatic injury induced by lead coupled with
      lipopolysaccharide.
AB  - BACKGROUND: In this study, we investigated the potential anti-inflammatory and
      antioxidative effects of sesamin on acute liver injury. Lead (Pb) causes
      oxidative damage and enhances the effects of low-dose lipopolysaccharide (LPS),
      inducing acute hepatic injury in rats. METHODS: Male Sprague-Dawley rats were
      given intraperitoneal injections of Pb acetate (5 mg/kg) and LPS (50 MUg/kg) to
      induce liver injury, and we tested the effects of oral administration of sesamin
      (10 mg/kg) on liver damage. To assess the extent of acute hepatic injury in the
      rats, we measured the anti-inflammatory and antioxidant markers and relevant
      signaling pathways: serum aspartate aminotransferase (AST), alanine
      aminotransferase (ALT), C-reactive protein (CRP), reactive oxygen species (ROS),
      tumor necrosis factor (TNF)-alpha, interleukin (IL)-1, IL-6, nitric oxide (NO),
      and cyclooxygenase-2 (COX-2), inducible NO synthase (iNOS) levels, mitogen
      activated protein kinases (MAPKs), c-Fos, and GADD45beta. RESULTS: Sesamin
      significantly decreased the serum AST, ALT, and CRP levels in the rat model. In
      the Pb and LPS-stressed rats, sesamin administration reduced the serum levels of
      TNF-alpha, IL-1, IL-6, NO, and ROS generation, and liver tissue expressions of c
      Jun N-terminal kinase (JNK), p38 MAPK, GADD45beta, COX-2, and iNOS. CONCLUSION:
      Collectively, these results demonstrate that sesamin is associated with
      antioxidant and anti-inflammatory activity. The observed effect of scavenging of
      ROS and NO and inhibiting the production of proinflammatory cytokines may be
      achieved through the suppression of COX-2, iNOS, and MAPK pathways in the acute
      hepatic injury rats.

PMID- 24726678
TI  - Hyperbaric oxygen therapy as an effective adjunctive treatment for chronic Lyme
      disease.
AB  - Lyme disease is the most commonly reported vector-borne illness in the United
      States, but it is relatively rare in Taiwan. Lyme disease can be treated with
      antibiotic agents, but approximately 20% of these patients experience persistent
      or intermittent subjective symptoms, so-called chronic Lyme disease (CLD). The
      mechanisms of CLD remain unclear and the symptoms related to CLD are difficult to
      manage. Hyperbaric oxygen therapy (HBOT) was applied in CLD therapy in the 1990s.
      However, reported information regarding the effectiveness of HBOT for CLD is
      still limited. Here, we present a patient with CLD who was successfully treated
      with HBOT.

PMID- 24726679
TI  - Performance and clinical validation of the RealStar MERS-CoV Kit for detection of
      Middle East respiratory syndrome coronavirus RNA.
AB  - BACKGROUND: A highly pathogenic human coronavirus causing respiratory disease
      emerged in the Middle East region in 2012. In-house molecular diagnostic methods
      for this virus termed Middle East respiratory syndrome coronavirus (MERS-CoV)
      allowed sensitive MERS-CoV RNA detection in patient samples. Fast diagnosis is
      important to manage human cases and trace possible contacts. OBJECTIVES: The aim
      of this study was to improve the availability of existing nucleic acid
      amplification-based diagnostic methods for MERS-CoV infections by providing a
      real-time RT-PCR kit, including an internal control and two target regions
      recommended by the World Health Organization (WHO). And to validate this kit
      (RealStar MERS-CoV RT-PCR kit 1.0, Altona Diagnostics GmbH, Hamburg, Germany)
      using clinical samples of one MERS-CoV case from Munich and respiratory samples
      of patients with other respiratory diseases. STUDY DESIGN: An internal
      amplification control was included into the RT-PCR assays targeting the genomic
      region upstream of the Envelope gene (upE) and within open reading frame (ORF)
      1A. Based on these assays, a ready-to-use real-time RT-PCR kit featuring both the
      upE and ORF1A assays was developed, validated and compared to the established in
      house versions. RESULTS: The performance of both RT-PCR assays included in the
      kit is comparable to the in-house assays. They show high analytical sensitivity
      (upE: 5.3 copies/reaction; ORF1A: 9.3 copies/reaction), no cross-reactivity with
      other respiratory pathogens and detected MERS-CoV RNA in patient samples in
      almost the same manner as the in-house versions. CONCLUSION: The kit is a
      valuable tool for assisting in the rapid diagnosis, patient management and
      epidemiology of suspected MERS-CoV cases.

PMID- 24726680
TI  - Effects of hydrochlorothiazide on the pharmacokinetics, pharmacodynamics, and
      tolerability of canagliflozin, a sodium glucose co-transporter 2 inhibitor, in
      healthy participants.
AB  - BACKGROUND: Many patients with type 2 diabetes mellitus (T2DM) also have
      hypertension, which is commonly treated with thiazide diuretics, including
      hydrochlorothiazide (HCTZ). Canagliflozin, a sodium glucose cotransporter 2
      inhibitor developed for the treatment of T2DM, lowers plasma glucose by
      inhibiting renal glucose reabsorption, thereby increasing urinary glucose
      excretion and mild osmotic diuresis. Because patients with T2DM are likely to
      receive concurrent canagliflozin and HCTZ, potential interactions were evaluated.
      OBJECTIVE: This study evaluated the effects of HCTZ on the pharmacokinetic and
      pharmacodynamic properties and tolerability of canagliflozin in healthy
      participants. METHODS: This Phase I, single-center, open-label, fixed-sequence, 2
      period study was conducted in healthy participants. During period 1, participants
      received canagliflozin 300 mg once daily for 7 days, followed by a 14-day washout
      period. During period 2, participants received HCTZ 25 mg once daily for 28 days,
      followed by canagliflozin 300 mg + HCTZ 25 mg once daily for 7 days. Blood
      samples were taken before and several times after administration on day 7 of
      period 1 and on days 28 and 35 of period 2 for canagliflozin and HCTZ
      pharmacokinetic analyses using LC-MS/MS. Blood and urine samples were collected
      for up to 24 hours after canagliflozin administration on day 1 of period 1 and
      day 35 of period 2 for pharmacodynamic glucose assessment. Tolerability was also
      evaluated. RESULTS: Thirty participants were enrolled (16 men, 14 women; all
      white; mean age, 43.7 years). Canagliflozin AUC during a dosing interval (T) at
      steady state (AUCtau,ss) and Cmax at steady state (Cmax,ss) were increased when
      canagliflozin was coadministered with HCTZ, with geometric mean ratios (90% CI)
      of 1.12 (1.08-1.17) and 1.15 (1.06-1.25), respectively. AUCtau,ss and Cmax,ss for
      HCTZ were similar with and without canagliflozin coadministration. The 24-hour
      mean renal threshold for glucose and mean plasma glucose were comparable for
      canagliflozin alone and coadministered with HCTZ. The change in 24-hour urine
      volume from baseline was -0.1 L with canagliflozin alone and 0.4 L with HCTZ
      alone and with canagliflozin + HCTZ. The overall incidence of adverse events
      (AEs) was higher with canagliflozin + HCTZ (69%) than with canagliflozin (47%) or
      HCTZ (50%) alone; most AEs were of mild severity. Overall, minimal changes in
      serum electrolytes (eg, sodium, potassium) were observed after coadministration
      of canagliflozin + HCTZ compared with individual treatments. CONCLUSIONS: Adding
      canagliflozin treatment to healthy participants on HCTZ treatment had no notable
      pharmacokinetic or pharmacodynamic effects; canagliflozin coadministered with
      HCTZ was generally well tolerated, with no unexpected tolerability concerns.
      ClinicalTrials.gov identifier: NCT01294631.

PMID- 24726681
TI  - Deconvolution of overlapping spectral polymer signals in size exclusion
      separation-diode array detection separations by implementing a multivariate curve
      resolution method optimized by alternating least square.
AB  - Peaks eluting from a size exclusion separation (SEC) are often not completely
      baseline-separated due to the inherent dispersity of the polymer. Lowering the
      flow rate is sometimes a solution to obtain a better physical separation, but
      results in a longer retention time, which is often not desirable. The
      chemometrical deconvolution method discussed in this work provides the
      possibility of calculating the contribution of each peak separately in the total
      chromatogram of overlapping peaks. An in-house-developed MATLAB script
      differentiates between compounds based on their difference in UV-spectrum and
      retention time, using the entire 3D retention time UV-spectrum. Consequently, the
      output of the script offers the calculated chromatograms of the separate
      compounds as well as their respective UV-spectrum, of which the latter can be
      used for peak identification. This approach is of interest to quantitate
      contributions of different polymer types with overlapping UV-spectra and
      retention times, as is often the case in, for example, copolymer or polymer blend
      analysis. The applicability has been proven on mixtures of different polymer
      types: polystyrene, poly(methyl methacrylate) and poly(ethoxyethyl acrylate).
      This paper demonstrates that both qualitative and quantitative analyses are
      possible after deconvolution and that alternating concentrations of adjacent
      peaks do not significantly influence the obtained accuracy. 

PMID- 24726682
TI  - Short-term mechanical circulatory support for recovery from acute right
      ventricular failure: clinical outcomes.
AB  - BACKGROUND: Acute right ventricular failure (ARVF) refractory to optimal medical
      management may require rescue therapy with mechanical circulatory support (MCS).
      The RV exhibits a greater capacity for rapid recovery than the left ventricle,
      making devices designed specifically for temporary RV MCS attractive. We report
      our experience with the Impella Right Direct (RD) and Right Peripheral (RP)
      temporary ventricular assist devices (Abiomed, Danvers, MA) in patients with
      ARVF. METHODS: We conducted a retrospective cohort study examining the clinical
      outcomes of consecutive patients supported with the Impella RD or RP at 2
      institutions during a 6-year period. RESULTS: During the study period, 18
      patients (67% men; mean age 57 +/- 10 years) received MCS, 15 with the Impella RD
      and 3 with the Impella RP. Before RV MCS, all patients required intravenous
      inotropes, 7 (39%) required inhaled nitric oxide, 7 (39%) required intra-aortic
      balloon counterpulsation, and 2 (11%) had experienced a cardiac arrest. Device
      implantation resulted in an improvement in cardiac index (2.1 +/- 0.1
      liters/min/m(2) pre-implant vs 2.6 +/- 0.2 liters/min/m(2) post-implant, p =
      0.04) and reduced central venous pressure (22 +/- 5 vs 15 +/- 4 mm Hg, p < 0.01).
      Fourteen (78%) patients recovered sufficient RV function to facilitate device
      explanation after 7 days (range, 2-19 days) of support, and 4 (22%) patients died
      on support after 6 days (range 1-11 days). Survival to 30 days was 72% and to 1
      year was 50%. At 1-year follow-up, the mean New York Heart Association functional
      classification was 1.3 +/- 0.5, and only 1 patient demonstrated severe RV
      dysfunction on echocardiography. CONCLUSIONS: Most patients with ARVF rapidly
      recover sufficient RV function to facilitate device explantation, highlighting an
      expanding role for minimally invasive temporary RV assist devices optimized for
      the treatment of recoverable ARVF.

PMID- 24726683
TI  - Delayed chest closure after lung transplantation: techniques, outcomes, and
      strategies.
AB  - BACKGROUND: Delayed chest closure (DCC) after lung transplantation is a viable
      option to be taken in the cases of prolonged cardiopulmonary bypass time,
      prolonged ischemic time, coagulopathic problems or oversized donor lung grafts.
      Decision-making for DCC in the operating room remains challenging to surgeons,
      because the impact of DCC on outcomes after lung transplantation has not yet been
      fully elucidated. METHODS: We performed a retrospective review of 90 lung
      transplantations with DCC and 783 cases with primary chest closure to clarify the
      reasons for DCC, complications of DCC, and the risk factors for adverse outcomes.
      RESULTS: The 30- and 90-day mortality in the DCC group was 7.8% and 9.9%,
      respectively. Early post-operative bleeding and severe primary graft dysfunction
      (PGD) were higher in the DCC group (p<0.05). In multivariate analysis, prolonged
      cardiopulmonary bypass use (>4 hours), post-operative extracorporeal oxygen
      requirement and use of a DCC technique with open skin and retracted ribs were
      significantly associated with mortality (p<0.05), whereas prolonged duration of
      DCC was not. In a matched cohort study to compare the results of a DCC technique
      with skin closure to similarly matched controls with primary closure, DCC
      contributed to significantly decreased incidence of severe PGD (9.6% vs. 26%,
      p<0.05), leading to an improved post-transplant survival and functional status as
      compared with primary closure. CONCLUSIONS: Our technical approaches to prevent
      possible problems in DCC cases are described. DCC can be safely performed with
      acceptable procedure-related risks. DCC should not be considered a sub-optimal
      option after lung transplantation.

PMID- 24726684
TI  - Lower-leg Kinesio tape reduces rate of loading in participants with medial tibial
      stress syndrome.
AB  - CONTEXT: Medial tibial stress syndrome (MTSS) is an overuse injury occurring
      among the physically active. Linked to increased strain on the medial tendons of
      the ankle, studies emphasize controlling medial foot loading in the management of
      this condition. Kinesio taping (KT) has gained popularity for treating
      musculoskeletal pathologies; however, its effect on MTSS remains uninvestigated.
      This study aimed to determine if healthy participants and patients with current
      or previous history of MTSS differ in the rate of loading, and if KT affects
      plantar pressures in these participants. METHODS: Twenty healthy participants and
      20 participants with current or previous history of MTSS were recruited and
      walked across a plantar pressure mat prior to KT application, immediately after
      application, and after 24-h of continued use. Time-to-peak force was measured in
      6 foot areas and compared across groups and conditions. RESULTS: ANOVA revealed a
      significant interaction between group, condition, and foot area (F = 1.990, p =
      0.033). MTSS participants presented with lower medial midfoot time-to-peak force
      before tape application (95%CI: 0.014-0.160%, p = 0.021) that significantly
      increased following tape application (p < 0.05). CONCLUSIONS: These results
      suggest that KT decreases the rate of medial loading in MTSS patients. Future
      research might assess mechanisms by which this effect is achieved.

PMID- 24726685
TI  - Chemical composition, antimicrobial activity against Staphylococcus aureus and a
      pro-apoptotic effect in SGC-7901 of the essential oil from Toona sinensis (A.
      Juss.) Roem. leaves.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Leaves of Toona sinensis (A. Juss.) Roem. (TSL),
      a popular vegetable in China, have anti-inflammatory, antidoting, and worm
      killing effects and are used in folk medicine for the treatment of enteritis,
      dysentery, carbuncles, boils, and especially abdominal tumors. Our aim was to
      investigate the in vitro antimicrobial activity against Staphylococcus aureus and
      anticancer property of the essential oil from TSL (TSL-EO), especially the pro
      apoptotic effect in SGC-7901. MATERIALS AND METHODS: TSL-EO obtained by
      hydrodistillation was analyzed by GC/MS and was tested in vitro against twenty
      clinically isolated strains of Staphylococcus aureus (SA 1-20), which were either
      methicillin-sensitive Staphylococcus aureus (MSSA) or methicillin-resistant
      Staphylococcus aureus (MRSA) and two standard strains viz. ATCC 25923 and ATCC
      43300. The anticancer activity of TSL-EO was evaluated in vitro against HepG2,
      SGC7901, and HT29 through MTT assay. Moreover, the apoptosis-inducing activity of
      TSL-EO in SGC7901 cells was determined by Hoechst 33324 staining and flow
      cytometry methods. Also, the apoptosis-related proteins viz. Bax, Bcl-2 and
      caspase-3 were detected by western-blotting. RESULTS: GC-MS analysis showed that
      TSL-EO contained a high amount of sesquiterpenes (84.64%), including copaene
      (8.27%), beta-caryophyllene (10.16%), caryophyllene (13.18%) and beta-eudesmene
      (5.06%). TSL-EO inhibited the growth of both MSSA and MRSA, with the lowest MIC
      values of 0.125 and 1mg/ml, respectively. Treatment with TSL-EO for 24h could
      significantly suppress the viability of three different cancer cell lines
      (P<0.05). Furthermore, the apoptosis-inducing activity of TSL-EO in SGC7901 cells
      increased in a dose-dependent manner, potentially resulting from the up-regulated
      expression of Bax, caspase-3 and down-regulated expression of Bcl-2. CONCLUSIONS:
      TSL-EO possessed antibacterial activity against Staphylococcus aureus and
      significant cytotoxicity against cancer cells and particularly prominent pro
      apoptotic activity in SGC7901 cells. These bioactivities were probably due to the
      high content of sesquiterpenes. Our results suggested that TSL-EO possessed
      potential health benefits and could serve as a promising natural food addictive.

PMID- 24726686
TI  - Multi-drug resistant oral Candida species isolated from HIV-positive patients in
      South Africa and Cameroon.
AB  - Candida species are a common cause of infection in immune-compromised HIV
      positive individuals, who are usually treated with the antifungal drug,
      fluconazole, in public hospitals in Africa. However, information about the
      prevalence of drug resistance to fluconazole and other antifungal agents on
      Candida species is very limited. This study examined 128 Candida isolates from
      South Africa and 126 Cameroonian Candida isolates for determination of species
      prevalence and antifungal drug susceptibility. The isolates were characterized by
      growth on chromogenic and selective media and by their susceptibility to 9
      antifungal drugs tested using the TREKTM YeastOne9 drug panel (Thermo Scientific,
      USA). Eighty-three percent (82.8%) of South African isolates were Candida
      albicans (106 isolates), 9.4% were Candida glabrata (12 isolates), and 7.8% were
      Candida dubliniensis (10 isolates). Of the Cameroonian isolates, 73.02% were C.
      albicans (92 isolates); 19.05% C. glabrata (24 isolates); 3.2% Candida tropicalis
      (4 isolates); 2.4% Candida krusei (3 isolates); 1.59% either Candida kefyr,
      Candida parapsilopsis, or Candida lusitaneae (2 isolates); and 0.79% C.
      dubliniensis (1 isolate). Widespread C. albicans resistance to azoles was
      detected phenotypically in both populations. Differences in drug resistance were
      seen within C. glabrata found in both populations. Echinocandin drugs were more
      effective on isolates obtained from the Cameroon than in South Africa. A multiple
      drug resistant C. dubliniensis strain isolated from the South African samples was
      inhibited only by 5-flucytosine in vitro on the YO9 panel. Drug resistance among
      oral Candida species is common among African HIV patients in these 2 countries.
      Regional surveillance of Candida species drug susceptibility should be undertaken
      to ensure effective treatment for HIV-positive patients. 

PMID- 24726687
TI  - The African variant of BKV in a Turkish renal transplant patient.
AB  - In renal transplant recipients, BK polyomavirus (BKV) is linked to nephropathy.
      BK virus genotypes have a strong geographic component. This paper presents the
      African variant of BKV in a Turkish renal transplant patient, which is a rare
      cause of infection in the Northern Hemisphere and, to our knowledge, the first
      case from Turkey. 

PMID- 24726688
TI  - Social network predictors of latrine ownership.
AB  - Poor sanitation, including the lack of clean functioning toilets, is a major
      factor contributing to morbidity and mortality from infectious diseases in the
      developing world. We examine correlates of latrine ownership in rural India with
      a focus on social network predictors. Participants from 75 villages provided the
      names of their social contacts as well as their own relevant demographic and
      household characteristics. Using these measures, we test whether the latrine
      ownership of an individual's social contacts is a significant predictor of
      individual latrine ownership. We also investigate whether network centrality
      significantly predicts latrine ownership, and if so, whether it moderates the
      relationship between the latrine ownership of the individual and that of her
      social contacts. Our results show that, controlling for the standard predictors
      of latrine ownership such as caste, education, and income, individuals are more
      likely to own latrines if their social contacts own latrines. Interaction models
      suggest that this relationship is stronger among those of the same caste, the
      same education, and those with stronger social ties. We also find that more
      central individuals are more likely to own latrines, but the correlation in
      latrine ownership between social contacts is strongest among individuals on the
      periphery of the network. Although more data is needed to determine how much the
      clustering of latrine ownership may be caused by social influence, the results
      here suggest that interventions designed to promote latrine ownership should
      consider focusing on those at the periphery of the network. The reason is that
      they are 1) less likely to own latrines and 2) more likely to exhibit the same
      behavior as their social contacts, possibly as a result of the spread of latrine
      adoption from one person to another. 

PMID- 24726690
TI  - Comparative analysis of immunization schedules using a novel adenovirus-based
      immunotherapeutic targeting hepatitis B in naive and tolerant mouse models.
AB  - Development of active targeted immunotherapeutics is a rapid developing field in
      the arena of chronic infectious diseases. The question of repeated, closely
      spaced administration of immunotherapeutics to achieve a rapid impact on the
      replicating agent is an important one. We analyzed here, using a prototype
      adenovirus-based immunotherapeutic encoding Core and Polymerase from the
      hepatitis B virus (Ad-HBV), the influence of closely spaced repeated
      immunizations on the level and quality of induced HBV-specific and vector
      specific immune responses in various mouse models. Ad-HBV, whether injected once
      or multiple times, was able to induce HBV- and adeno-specific T cells both in HBV
      free mice and in a HBV tolerant mouse model. Adenovirus-specific T cell responses
      and titers of neutralizing anti-Ad5 antibodies increased from time of the 3rd
      injection. Interestingly, single or multiple Ad-HBV injections resulted in
      detection of Polymerase-specific functional T cells in HBV tolerant mice. Overall
      no modulation of the levels of HBV-specific cytokine-producing
      (IFNgamma/TNFalpha) and cytolytic T cells was observed following repeated
      administrations (3 or 6 weekly injections) when compared with levels detected
      after a single injection with the exception of two markers: 1. the proportion of
      HBV-specific IFNgamma-producing cells bearing the CD27+/CD43+ phenotype appeared
      to be sustained in C57BL/6J mice following 6 weekly injections; 2. the percentage
      of IFNgamma/TNFalpha Core-specific producing cells observed in spleens of HLA-A2
      mice as well as of that specific of Polymerase observed in livers of HBV tolerant
      mice was maintained. In addition, percentage of HBV-specific T cells expressing
      PD-1 was not increased by multiple injections. Overall these data show that,
      under experimental conditions used, rapid, closely spaced administrations of an
      adenovirus-based HBV immunotherapeutics does not inhibit induced T-cell responses
      including in a HBV-tolerant environment. 

PMID- 24726691
TI  - Effects of resveratrol and other wine polyphenols on the proliferation, apoptosis
      and androgen receptor expression in LNCaP cells.
AB  - PURPOSE: To address the effect of resveratrol and other red wine polyphenols on
      cell proliferation, apoptosis and androgen receptor (AR) expression in human
      prostate cancer LNCaP cells. MATERIALS AND METHODS: LNCaP cells (5 * 102) were
      cultured in microtiter plate modules and treated with gallic acid, tannic acid
      and quercetin (1, 5 and 10 MUM), rutin and morin (25, 50 and 75 MUM) and
      resveratrol (5, 10 and 25 MUM). To address the extent of proliferation at 24, 48,
      72 and 96 hours, a colorimetric immunoassay method was used. An activity caspase
      3/7 detection assay was used to disclose apoptosis at 24, 48 and 72 hours. AR
      mARN levels were determined by real time RT-PCR. RESULTS: All polyphenols studied
      significantly inhibited (P<.05) cell proliferation compared to control. However,
      there were moderate differences between them. Resveratrol was the strongest
      inhibitor at different times and doses. Also, caspase-3 and caspase-7 activity
      was significantly higher (P<.05) than control in the presence of all the
      compounds, but the earlier response was achieved by resveratrol. Resveratrol,
      quercetin and morin were the only nutrients that significantly inhibited AR mRNA
      expression. Again resveratrol produced the highest inhibition (90-250 times less
      than control), followed by morin (67-100 times) and quercetin (55-91 times).
      CONCLUSIONS: All polyphenols studied showed important antiproliferative effects
      and induced apoptosis when added to LNCaP cells culture. We confirm that
      resveratrol, morin and quercetin may achieve such effect through reduced
      expression of AR. The synergistic effects of these compounds and their potential
      to prevent progression of hormone-dependent prostate cancer merit further study.

PMID- 24726692
TI  - Usefulness of pH monitoring in predicting the survival status of patients with
      scleroderma awaiting lung transplantation.
AB  - BACKGROUND: Patients with scleroderma and end-stage lung disease (ESLD) have a
      very high prevalence of gastroesophageal reflux disease (GERD). Because GERD has
      been associated with aspiration in those with ESLD, and because those with
      scleroderma are particularly prone to develop severe GERD, there is some concern
      that GERD may contribute to shorten survival in patients with scleroderma
      awaiting lung transplantation. Therefore, we hypothesized that esophageal pH
      monitoring could predict survival of those with scleroderma and ESLD awaiting
      lung transplantation and that the severity of reflux can impact survival.
      METHODS: We conducted a retrospective analysis of all scleroderma patients
      referred for lung transplantation who underwent esophageal manometry and pH
      monitoring since August 2008. We identified 10 patients in whom we calculated and
      compared the area under the curve for each receiver operating characteristic
      curve of the following variables: DeMeester score, forced expiratory volume in 1
      s (FEV1), %predicted FEV1, forced vital capacity (FVC), %predicted FVC, diffusion
      capacity for carbon monoxide (DLco), and %predicted DLco. RESULTS: The DeMeester
      score nominally outperformed FEV1, FVC, and DLco. Receiver operating
      characteristic curve analysis was also used to define the optimal DeMeester score
      (65.2) in differentiating survival status, as determined by maximizing
      sensitivity and specificity. Based on this value, we calculated the 1-y survival
      from the time of the esophageal function testing, which was 100% in seven
      patients with a DeMeester score of <65.2, and 33% in three patients with a score
      >65.2 (P = 0.01). The latter patients had greater total time pH < 4, greater time
      pH < 4 in the supine position, greater total episodes of reflux, and higher
      prevalence of absent peristalsis. The single survivor with a DeMeester score >70
      had also proximal reflux, underwent antireflux surgery, and is alive 1201 d after
      transplant. CONCLUSIONS: Our study shows that esophageal pH monitoring can
      predict survival status in patients with scleroderma awaiting lung
      transplantation and that the severity of reflux can impact the 1-y survival rate.
      Therefore, esophageal pH monitoring should be considered early in patients with
      scleroderma and ESLD, as this test could appropriately identify those in whom
      laparoscopic antireflux surgery should be performed quicker to prevent GERD and
      its detrimental effects in patients awaiting lung transplantation.

PMID- 24726693
TI  - Healing of two microarterial anastomoses with diameter mismatch.
AB  - BACKGROUND: The use of fascial perforating vessels as recipients for
      microvascular composite tissue autotransplants has led to vessel diameter
      discrepancy becoming an increasingly common finding. Little evidence, however, is
      available to direct the choice of anastomotic technique where a discrepancy
      exists. We have been studying two methods of anastomosing arteries where a small
      to-large discrepancy exists-a 45 degrees  section of the smaller vessel, and
      invaginating the smaller vessel inside the larger. As part of this work, this
      study examines intimal hyperplasia and healing of the two methods. MATERIALS AND
      METHODS: A previously described paired Wistar rat femoral axis model was used.
      Anastomoses were performed, one on each side, and specimens were harvested in
      groups at 24 h, 1 wk, 6 wk, and 8 mo. Inflammation, necrosis, and fibrosis in
      each layer of the vessel wall and intimal hyperplasia were each scored by an
      assessor blinded to the group and anastomotic technique. RESULTS: Significant
      differences in healing were found. The invagination technique induced less
      inflammation, and caused less endothelial and medial necrosis than the oblique
      cut end-to-end method. Intimal hyperplasia was most pronounced at 6 wk, but no
      evidence of a difference in the severity of intimal hyperplasia between the two
      methods was found. CONCLUSIONS: The invaginating anastomosis causes less
      inflammation and less vessel wall necrosis than the oblique end-to-end method in
      this model. This finding, alongside results from previous work, suggests that
      this is the better method to deal with a small-to-large microarterial diameter
      discrepancy in the range 1:1.5 to 1:2.5.

PMID- 24726694
TI  - Incidence of pyometra in Swedish insured cats.
AB  - Pyometra is a clinically relevant problem in intact female cats and dogs. The
      etiology is similar in both animal species, with the disease caused by bacterial
      infection of a progesterone-sensitized uterus. Here, we studied pyometra in cats
      with the aim to describe the incidence and probability of developing pyometra
      based on age and breed. The data used were reimbursed claims for veterinary care
      insurance or life insurance claims or both in cats insured in a Swedish insurance
      database from 1999 to 2006. The mean incidence rate (IR) for pyometra was about
      17 cats per 10,000 cat years at risk (CYAR). Cats with pyometra were diagnosed at
      a median age of 4 years and a significant breed effect was observed. The breed
      with the highest IR (433 cats per 10,000 CYAR) was the Sphynx, and other breeds
      with IR over 60 cats per 10,000 CYAR were Siberian cat, Ocicat, Korat, Siamese,
      Ragdoll, Maine coon, and Bengal. Pyometra was more commonly diagnosed with
      increasing age, with a marked increase in cats older than 7 years. The mean case
      fatality rate in all cats was 5.7%, which is slightly higher than corresponding
      reports in dogs of 3% to 4%. Geographical location (urban or rural) did not
      affect the risk of developing the disease. The present study provides information
      of incidence and probability of developing pyometra based on age, breed, and
      urban or rural geographical location. These data may be useful for designing cat
      breeding programs in high-risk breeds and for future studies of the genetic
      background of the disease. 

PMID- 24726695
TI  - Results of the 4th scientific workshop of the ECCO (Group II): markers of
      intestinal fibrosis in inflammatory bowel disease.
AB  - The fourth scientific workshop of the European Crohn's and Colitis Organization
      (ECCO) focused on intestinal fibrosis in inflammatory bowel disease (IBD). The
      objective was to better understand basic mechanisms and markers of intestinal
      fibrosis as well as to suggest new therapeutic targets to prevent or treat
      fibrosis. The results of this workshop are presented in three separate
      manuscripts. This section describes markers of fibrosis in IBD, identifies
      unanswered questions in the field and provides a framework for future studies
      addressing the unmet needs in the field of intestinal fibrosis. 

PMID- 24726697
TI  - Bioassay guided isolation and identification of anti-Acanthamoeba compounds from
      Tunisian olive leaf extracts.
AB  - Pathogenic Acanthamoeba strains are causative agents of Granulomatous Amoebic
      Encephalitis (GAE) and Acanthamoeba keratitis (AK) worldwide. The existence of
      the cyst stage complicates Acanthamoeba therapy as it is highly resistant to
      antibiotics and physical agents. The aim of this study was to investigate the
      activity of Limouni olive leaf cultivar against the trophozoite stage of
      Acanthamoeba. The ethyl acetate and methanol extracts of this variety were tested
      against Acanthamoeba castellanii Neff. The ethyl acetate extract of olive leaf
      was the most active showing an IC50 of 5.11+/-0.71MUg/ml of dry extract. Bio
      guided fractionation of this extract was conducted and led to the identification
      of three active compounds namely oleanolic and maslinic acids and oleuropein
      which could be used for the development of novel therapeutic approaches against
      Acanthamoeba infections. 

PMID- 24726698
TI  - Encystment in Acanthamoeba castellanii: a review.
AB  - Differentiation of Acanthamoeba castellanii trophozoites involves massive
      turnover of cellular components and remodelling of organelle structure and
      function so as to produce a cryptobiotic cell, resistant to desiccation, heat,
      freezing, and chemical treatments. This review presents a summary of a decade of
      research on the most studied aspects of the biochemistry of this process, with
      emphasis on problems of biocide and drug resistances, putative new targets,
      molecular and cell biology of the process of encystment, and the characteristics
      of the encysted state. As well as the intrinsic pathogenicity of the organism
      towards the cornea, and the ability of related species to invade the human brain,
      its propensity for harbouring and transmitting pathogenic bacteria and viruses is
      considerable and leads to increasing concerns. The long-term survival and
      resistance of cysts to drugs and biocides adds another layer of complexity to the
      problem of their elimination. 

PMID- 24726696
TI  - Risk of colectomy in patients with ulcerative colitis under thiopurine treatment.
AB  - BACKGROUND AND AIMS: Little is known about the risk factors of colectomy in
      patients with ulcerative colitis (UC) under thiopurine treatment. The aim of the
      study was to determine the prevalence and the predictive risk factors of
      colectomy in an extensive cohort of patients with UC treated with thiopurines in
      Spain. METHODS: Among 5753 UC patients, we identified those diagnosed between
      1980 and 2009 and treated with azathioprine or mercaptopurine (AZA/MP). We
      analyzed the age at diagnosis, familial history of IBD, extraintestinal
      manifestations (EIMs), disease extent, smoking status and treatment requirements
      (AZA/MP, cyclosporine (CsA) or anti-TNFalpha). Colectomies for dysplasia or
      cancer were excluded. Survival analysis and Cox proportional hazard regression
      were performed. Results were reported as hazard ratios (HR) with 95% CI. RESULTS:
      Among the 1334 cases included, 119 patients (8.9%) required colectomy after a
      median time of 26 months (IQR 12-42) after AZA/MP initiation. Independent
      predictors of colectomy were: Extensive UC (HR 1.7, 95% CI: 1.1-2.6), EIMs (HR
      1.5, 95% CI: 1.0-2.4), need for antiTNFalpha (HR 2.3, 95% CI: 1.5-3.4) and need
      for CsA (HR 2.4, 95% CI: 1.6-3.7). Patients requiring early introduction of
      AZA/MP had an increased risk of colectomy with a HR of 4.9 (95% CI: 3.2-7.8) when
      AZA/MP started in the first 33 months after UC diagnosis. CONCLUSIONS: Nearly one
      tenth of patients with UC under thiopurines require colectomy. Extensive UC,
      EIMs, need for CsA or anti-TNFalpha ever and an early need for AZA/MP treatment
      were associated with a higher risk of colectomy. These risk factors of colectomy
      could help to stratify risk in further controlled studies in UC.

PMID- 24726699
TI  - Combined drug therapy in the management of granulomatous amoebic encephalitis due
      to Acanthamoeba spp., and Balamuthia mandrillaris.
AB  - Granulomatous amoebic encephalitis (GAE) is caused by two protist pathogens,
      Acanthamoeba spp., and Balamuthia mandrillaris. Although rare, it almost always
      results in death. In the present study, amoebae were treated with various
      combinations of clinically-approved drugs, targeting vital cellular receptors and
      biochemical pathways. The results revealed that among the seven different
      combinations tested, three proved highly effective against both Acanthamoeba
      castellanii as well as B. mandrillaris at a concentration of 100MUM. These
      combinations included (i) prochlorperazine plus loperamide; (ii) prochlorperazine
      plus apomorphine; and (iii) procyclidine plus loperamide. In viability assays,
      none of the drug-treated amoebae emerged as viable trophozoites, suggesting
      irreversible amoebicidal effects. Four combinations of drugs tested showed varied
      potency against A. castellanii and B. mandrillaris at 100MUM. The combination of
      haloperidol and loperamide was highly effective against A. castellanii at 100MUM,
      but potent effects against B. mandrillaris were observed only at 250MUM. Digoxin
      and amlodipine were effective against A. castellanii and B. mandrillaris at
      100MUM and 250MUM, respectively. In contrast, the combination of apomorphine and
      haloperidol was effective against B. mandrillaris and A. castellanii at 100MUM
      and 250MUM, respectively. At 100MUM, the combination of procyclidine and
      amiodarone was effective against neither A. castellanii nor B. mandrillaris. In
      this case, amoebicidal properties were observed at 750MUM for A. castellanii, and
      950MUM for B. mandrillaris. As these drugs are used clinically against non
      communicable diseases, the findings reported here have the potential to be tested
      in a clinical setting against amoebic encephalitis caused by A. castellanii and
      B. mandrillaris. 

PMID- 24726700
TI  - Single amino acid substitutions on the needle tip protein IpaD increased Shigella
      virulence.
AB  - Infection of colonic epithelial cells by Shigella is associated with the type III
      secretion system, which serves as a molecular syringe to inject effectors into
      host cells. This system includes an extracellular needle used as a conduit for
      secreted proteins. Two of these proteins, IpaB and IpaD, dock at the needle tip
      to control secretion and are also involved in the insertion of a translocation
      pore into host cell membrane allowing effector delivery. To better understand the
      function of IpaD, we substituted thirteen residues conserved among homologous
      proteins in other bacterial species. Generated variants were tested for their
      ability to surface expose IpaB and IpaD, to control secretion, to insert the
      translocation pore, and to invade host cells. In addition to a first group of
      seven ipaD variants that behaved similarly to the wild-type strain, we identified
      a second group with mutations V314D and I319D that deregulated secretion of all
      effectors, but remained fully invasive. Moreover, we identified a third group
      with mutations Y153A, T161D, Q165L and Y276A, that exhibited increased levels of
      translocators secretion, pore formation, and cell entry. Altogether, our results
      offer a better understanding of the role of IpaD in the control of Shigella
      virulence. 

PMID- 24726701
TI  - Segmentation precision of abdominal anatomy for MRI-based radiotherapy.
AB  - The limited soft tissue visualization provided by computed tomography, the
      standard imaging modality for radiotherapy treatment planning and daily
      localization, has motivated studies on the use of magnetic resonance imaging
      (MRI) for better characterization of treatment sites, such as the prostate and
      head and neck. However, no studies have been conducted on MRI-based segmentation
      for the abdomen, a site that could greatly benefit from enhanced soft tissue
      targeting. We investigated the interobserver and intraobserver precision in
      segmentation of abdominal organs on MR images for treatment planning and
      localization. Manual segmentation of 8 abdominal organs was performed by 3
      independent observers on MR images acquired from 14 healthy subjects. Observers
      repeated segmentation 4 separate times for each image set. Interobserver and
      intraobserver contouring precision was assessed by computing 3-dimensional
      overlap (Dice coefficient [DC]) and distance to agreement (Hausdorff distance
      [HD]) of segmented organs. The mean and standard deviation of intraobserver and
      interobserver DC and HD values were DC(intraobserver) = 0.89 +/- 0.12,
      HD(intraobserver) = 3.6mm +/- 1.5, DC(interobserver) = 0.89 +/- 0.15, and
      HD(interobserver) = 3.2mm +/- 1.4. Overall, metrics indicated good
      interobserver/intraobserver precision (mean DC > 0.7, mean HD < 4mm). Results
      suggest that MRI offers good segmentation precision for abdominal sites. These
      findings support the utility of MRI for abdominal planning and localization, as
      emerging MRI technologies, techniques, and onboard imaging devices are beginning
      to enable MRI-based radiotherapy.

PMID- 24726702
TI  - Neonatal necrotizing enterocolitis adversely affects neural conduction of the
      rostral brainstem in preterm babies.
AB  - OBJECTIVE: Necrotizing enterocolitis (NEC) is a devastating neonatal disease,
      often leading to long term neurodevelopmental impairment. The effect of NEC on
      the immature brain remains not fully understood. We test the hypothesis that NEC
      adversely affects functional integrity, particularly neural conduction, of the
      preterm brainstem. METHODS: Thirty-two preterm NEC babies (30-36weeks gestation)
      were recruited at term age. Maximum length sequence brainstem auditory evoked
      response was recorded and analysed with click rates 91-910/s at term age. The
      results were compared with normal term babies and age-matched healthy preterm
      babies. RESULTS: Wave V latency, I-V and III-V intervals, and III-V/I-III
      interval ratio differed significantly among the three groups of babies at all
      click rates 91-910/s. Compared with normal term babies, preterm NEC babies showed
      significant increase in all these MLS BAER variables at all rates, with no
      apparent abnormalities in wave I and III latencies and I-III interval. All these
      abnormalities were more significant at higher than at lower click rates. No
      notable abnormalities were seen in wave amplitudes. Compared with age-matched
      healthy preterm babies, NEC babies showed similar abnormalities, although the
      abnormalities were relatively less significant. CONCLUSIONS: MLS BAER components
      that mainly reflect neural conduction in the more central regions of the auditory
      brainstem were abnormal in preterm NEC babies, although those components that
      mainly reflect peripheral function were generally normal. SIGNIFICANCE: Neonatal
      NEC adversely affects myelination of the more rostral or central regions of the
      immature brainstem, resulting in delayed or impaired neural conduction, but
      spares the more peripheral regions.

PMID- 24726703
TI  - Field evaluation of Abbott Real Time HIV-1 Qualitative test for early infant
      diagnosis using dried blood spots samples in comparison to Roche COBAS
      Ampliprep/COBAS TaqMan HIV-1 Qual test in Kenya.
AB  - Timely diagnosis and treatment of infants infected with HIV are critical for
      reducing infant mortality. High-throughput automated diagnostic tests like Roche
      COBAS AmpliPrep/COBAS TaqMan HIV-1 Qual Test (Roche CAPCTM Qual) and the Abbott
      Real Time HIV-1 Qualitative (Abbott Qualitative) can be used to rapidly expand
      early infant diagnosis testing services. In this study, the performance
      characteristics of the Abbott Qualitative were evaluated using two hundred dried
      blood spots (DBS) samples (100 HIV-1 positive and 100 HIV-1 negative) collected
      from infants attending the antenatal facilities in Kisumu, Kenya. The Abbott
      Qualitative results were compared to the diagnostic testing completed using the
      Roche CAPCTM Qual in Kenya. The sensitivity and specificity of the Abbott
      Qualitative were 99.0% (95% CI: 95.0-100.0) and 100.0% (95% CI: 96.0-100.0),
      respectively, and the overall reproducibility was 98.0% (95% CI: 86.0-100.0). The
      limits of detection for the Abbott Qualitative and Roche CAPCTM Qual were 56.5
      and 6.9copies/mL at 95% CIs (p=0.005), respectively. The study findings
      demonstrate that the Abbott Qualitative test is a practical option for timely
      diagnosis of HIV in infants. 

PMID- 24726704
TI  - Diagnostic accuracy evaluation of the ImmunoFlow HCV rapid immunochromatographic
      test for the detection of hepatitis C antibodies.
AB  - 2% of the world's population lives with a hepatitis C virus (HCV) infection with
      highest rates in developing countries. The most common mode of transmission takes
      place via unsafe blood transfusions and unsafe therapeutic injections. Thus,
      screening potential blood donors for hepatitis C infection is a must to ensure
      safe blood transfusions. Rapid immunochromatographic tests are the best suitable
      test format to be used for screening for blood donors in resource-limited
      settings. The ImmunoFlow HCV from Core Diagnostics was evaluated at the Paul
      Ehrlich-Institute, Germany for its test accuracy on three seropanels. Panel 1
      consisted of 26 HCV positive and 55 negative samples, panel 2 of 193 HCV positive
      samples. Panel 3 contained 116 samples of 10 patients during seroconversion
      period. 39 of these 116 samples were characterized as HCV positive. The HCV
      ImmunoFlow had a sensitivity of 100% (95% CI: 93.5-100) and a specificity of 100%
      (95% CI: 86.8-100) when samples of panel 1 were tested. 191 samples of the 193
      samples in panel 2 were correctly by the HCV Immunoflow, resulting in a
      sensitivity of 99.0%. 9 of 10 HCV infections were detected by the HCV ImmunoFlow
      when panel 3 was used. This evaluation revealed good sensitivity of the HCV
      ImmunoFlow test from and compares favorably with the results from the WHO
      evaluation and a systematic review conducted of field evaluations of Hepatitis C
      rapid diagnostic and other point of care tests. 

PMID- 24726705
TI  - Intrathecal injection of selected peptide Myr-RC-13 attenuates bone cancer pain
      by inhibiting KIF17 and NR2B expression.
AB  - Although bone cancer pain is a common intractable clinical symptom, its
      underlying mechanisms are still elusive. Accumulating evidence reveals that the N
      methyl-D-aspartate (NMDA) receptor containing a 2B subunit (NR2B) in the spinal
      cord contributes to bone cancer pain. Our preliminary study demonstrated that
      intrathecal injection of fusion peptide Myr-RC-13 could disrupt spinal
      KIF17/mLin10 interaction, which is an essential component of KIF17-mediated NR2B
      transport. Here we report a means by infusion of the selected peptide Myr-RC-13
      intrathecally to attenuate bone cancer pain. The results showed that inoculation
      of fibrosarcoma NCTC 2472 cells into the femur cavity of C3H/HeJ mice induced
      progressive bone cancer pain and resulted in up-regulation of KIF17 and NR2B in
      the spinal cord. In addition, repetitive spinal delivery of Myr-RC-13 relieved
      bone cancer-related mechanical allodynia and spontaneous pain behaviors, and down
      regulated expression of spinal KIF17 and NR2B. Finally, our results demonstrated
      that selected peptide Myr-RC-13 was able to attenuate bone cancer pain via
      decreasing spinal KIF17 and NR2B expressions. Therefore, selected peptide Myr-RC
      13 might be a potential analgesic strategy for bone cancer pain.

PMID- 24726706
TI  - Neuroprotective effects of the andrographolide analogue AL-1 in the MPP+/MPTP
      induced Parkinson's disease model in vitro and in mice.
AB  - The andrographolide-lipoic acid conjugate AL-1 is a newly synthesized molecule by
      covalently linking andrographolide (Andro) with alpha-lipoic acid (LA). In the
      present work, the neuroprotective effect of AL-1 was investigated in vitro and in
      a mouse model of the Parkinson's disease (PD). We found that AL-1 significantly
      prevented 1-methyl-4-phenylpyridinium (MPP(+))-induced neurotoxicity in SH-SY5Y
      cells and primary cerebellar granule neurons. In a mouse model of Parkinson's
      disease, AL-1 rescued 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP)
      induced loss of tyrosine hydroxylase (TH)-positive neurons, improved the
      behavioral impairment, and elevated the striatal levels of dopamine and its
      metabolites 3,4-dihydroxyphenylacetic acid. Furthermore, AL-1 remarkably lowered
      the nitric oxide and malondialdehyde levels while increased the superoxide
      dismutase level in the substantial nigra of MPTP-treated mice. The immunoblotting
      data showed that AL-1 significantly ameliorated the decreased expression of TH
      protein in the substantial nigra and inhibited the up-regulation of
      phosphorylated NF-kappaB p65 in vitro and in vivo. Taken together, AL-1 exerted
      neuroprotective effect in vitro and in animal model of PD through anti-oxidation
      and inhibition of NF-kappaB activation. 

PMID- 24726707
TI  - Antiallodynic and antihyperalgesic activity of 3-[4-(3-trifluoromethyl-phenyl)
      piperazin-1-yl]-dihydrofuran-2-one compared to pregabalin in chemotherapy-induced
      neuropathic pain in mice.
AB  - BACKGROUND: Anticancer drugs - oxaliplatin (OXPT) and paclitaxel (PACLI) cause
      painful peripheral neuropathy activating Transient Receptor Potential (TRP)
      channels. Here we investigated the influence of 3-[4-(3-trifluoromethyl-phenyl)
      piperazin-1-yl]-dihydrofuran-2-one (LPP1) and pregabalin on nociceptive
      thresholds in neuropathic pain models elicited by these drugs. Pharmacokinetics
      of LPP1 and its ability to attenuate neurogenic pain caused by TRP agonists:
      capsaicin and allyl isothiocyanate (AITC) were also investigated. METHODS:
      Antiallodynic and antihyperalgesic effects of intraperitoneally administered LPP1
      and pregabalin were tested in the von Frey, hot plate and cold water tests. The
      influence of LPP1 on locomotor activity and motor coordination was assessed using
      actimeters and rotarod. Serum and tissue concentrations of LPP1 were measured
      using the HPLC method with fluorimetric detection. RESULTS: In OXPT-treated mice
      LPP1 and pregabalin dose-dependently reduced tactile allodynia (41-106% and 6
      122%, respectively, p<0.01). At the dose of 10mg/kg LPP1 attenuated cold
      allodynia. In PACLI-treated mice LPP1 and pregabalin reduced tactile allodynia by
      12-63% and 8-50%, respectively (p<0.01). Both drugs did not affect cold
      allodynia, whereas pregabalin (30 mg/kg) attenuated heat hyperalgesia (80% vs.
      baseline latency time; p<0.01). No motor impairments were observed in LPP1 or
      pregabalin-treated neuropathic mice in the rotarod test, while severe sedation
      was noted in the locomotor activity test. LPP1 reduced pain induced by capsaicin
      (51%; p<0.01) and AITC (41%; p<0.05). The mean serum concentration of LPP1
      measured 30 min following i.p. administration was 7904.6 +/- 1066.1 ng/ml.
      Similar levels were attained in muscles, whereas brain concentrations were 62%
      lower. Relatively high concentrations of LPP1 were also determined in the
      cerebrospinal fluid and the sciatic nerve. CONCLUSIONS: LPP1 and pregabalin
      reduce pain in OXPT and PACLI-treated mice. This activity of LPP1 might be in
      part attributed to the inhibition of TRPV1 and TRPA1 channels, but also central
      mechanisms of action cannot be ruled out.

PMID- 24726708
TI  - Acute intraperitoneal injection of caffeine improves endurance exercise
      performance in association with increasing brain dopamine release during
      exercise.
AB  - The purpose of this study was to examine changes of thermoregulation,
      neurotransmitters in the preoptic area and anterior hypothalamus (PO/AH), which
      is the thermoregulatory center, and endurance exercise performance after the
      intraperitoneal injection of caffeine in rats. Core body temperature (Tcore),
      oxygen consumption (VO2) and tail skin temperature (Ttail) were measured. A
      microdialysis probe was inserted in the PO/AH, and samples for the measurements
      of extracellular dopamine (DA), noradrenaline (NA) and serotonin (5-HT) levels
      were collected. During the rest experiment, 1 h after baseline collections in the
      chamber (23  degrees C), the rats were intraperitoneally injected with saline, or
      3 mg kg(-1) or 10 mg kg(-1) caffeine. The duration of the test was 4 h. During
      the exercise experiment, baseline collections on the treadmill were obtained for
      1 h. One hour before the start of exercise, rats were intraperitoneally injected
      with either 10 mg kg(-1) caffeine (CAF) or saline (SAL). Animals ran until
      fatigue at a speed of 18 m min(-1), at a 5% grade, on the treadmill in a normal
      environment (23  degrees C). At rest, 3 mg kg(-1) caffeine did not influence
      Tcore, Ttail, VO2, extracellular DA, NA and 5-HT. 10 mg kg(-1) caffeine caused
      significant increases in Tcore, VO2, Ttail and extracellular DA in the PO/AH. In
      addition, 10 mg kg(-1) caffeine increased the run time to fatigue (SAL: 104.4 +/-
      30.9 min, CAF: 134.0 +/- 31.1 min, p<0.05). The combination of caffeine and
      exercise increased Tcore, VO2, Ttail and extracellular DA in the PO/AH. NA
      increased during exercise, while neither caffeine nor exercise changed 5-HT.
      These results indicate that caffeine has ergogenic and hyperthermic effects, and
      these effects may be related to changes of DA release in the brain.

PMID- 24726709
TI  - 5-HT1A receptor activation reduces fear-related behavior following social defeat
      in Syrian hamsters.
AB  - Social defeat leads to selective avoidance of familiar opponents as well as
      general avoidance of novel, non-threatening intruders. Avoidance of familiar
      opponents represents a fear-related memory whereas generalized social avoidance
      indicates anxiety-like behavior. We have previously shown that serotonin
      signaling alters responses to social defeat in Syrian hamsters, although it is
      unclear whether serotonin modulates defeat-induced fear, anxiety, or both. In
      this study we focus on 5-HT1A receptors, in part, because their activation had
      been linked to the acquisition of conditioned fear. We hypothesized that
      pharmacological activation of 5-HT1A receptors prior to social defeat would
      reduce avoidance of familiar opponents and impair Arc expression in the
      basolateral amygdala (BLA), but not alter anxiety-like behavior. We administered
      8-OH-DPAT, a 5-HT1A receptor agonist, prior to 3, 5-minute social defeats and 24h
      later exposed hamsters to a social interaction test to measure the conditioned
      defeat response immediately followed by either a Y-maze test or an open field
      test. In a separate experiment, we administered 8-OH-DPAT prior to 3, 5-minute
      social defeats and later removed the brains for Arc immunohistochemistry. Social
      defeat increased the number of Arc immunopositive cells in the central amygdala
      (CeA), prelimbic cortex (PL), and BLA, and 8-OH-DPAT treatment reduced Arc
      immunoreactivity in the PL. These results suggest that 5-HT1A receptor activation
      impairs the fear memory associated with social defeat, but does not alter defeat
      induced anxiety. Overall, 5-HT1A receptor activation may impair Arc expression in
      select brain regions such as the PL and thereby disrupt the development of a fear
      memory essential for the conditioned defeat response. 

PMID- 24726710
TI  - Refined biokinetic model for humans exposed to cobalt dietary supplements and
      other sources of systemic cobalt exposure.
AB  - An updated biokinetic model for human exposures to cobalt (Co) was developed
      based on a comprehensive set of human pharmacokinetics data collected from five
      male and five female volunteers who ingested ~1 mg Co/day of a Co supplement for
      3 months. Three key experimental observations from the human dosing studies were
      incorporated into the model: (1) an increase in the measured fraction of large
      molecular serum protein bound Co from 95% during dosing to 99% after dosing; (2)
      a linear decrease in Co red blood cell concentration after dosing; and (3) Co
      renal clearance consistent with estimated glomerular filtration rates and free
      Co2+ concentration. The model was refined by adding compartments accounting for
      (1) albumin bound Co in intravascular fluid (serum); (2) albumin bound Co in
      extravascular fluid with physiologic exchange rates of albumin bound Co between
      extravascular and intravascular fluid; and (3) a novel sequential cascade of
      compartments representing red blood cell ages between 1 and 120 days. Reasonable
      agreement between the modeled and measured urine, serum, and whole blood
      concentrations were observed (r>0.84, slope=0.79-1.0) with gastrointestinal
      absorption rates between 9% and 66%. In addition, model predictions agreed well
      with data from several external studies representing healthy human volunteers,
      dialysis patients, anephric patients, a Co-poisoning incident and whole body
      retention studies. Our revised model considerably improves the state of knowledge
      on human Co kinetics, and should be helpful for evaluating elevated blood Co
      concentrations in currently exposed populations, such as metal-on-metal (MoM) hip
      implant patients.

PMID- 24726711
TI  - Leg actigraphy to quantify periodic limb movements of sleep: a systematic review
      and meta-analysis.
AB  - Periodic limb movements of sleep (PLMS) are repetitive, stereotyped movements
      that can disrupt sleep and result in insomnia, non-restorative sleep, and/or
      daytime sleepiness. Currently, polysomnography is the gold standard and only
      clinically acceptable means of quantifying PLMS. Leg-worn actigraphy is an
      alternative method of measuring PLMS, which may circumvent many of the economic
      and technical limitations of polysomnography to quantify nocturnal leg movements.
      However, the use of leg actigraphy as a diagnostic means of assessing PLMS has
      not been systematically evaluated. In this review, the use of leg-worn actigraphy
      to measure PLMS is systematically evaluated, using both qualitative and
      quantitative assessment. Findings demonstrate significant heterogeneity among a
      limited number of studies in terms of type of actigraph utilized, position of the
      device on the lower extremity, and methods employed to count PLMS. In general,
      common accelerometers vary in their sensitivity and specificity to detect PLMS,
      which is likely related to the technical specifications of a given device. A
      current limitation in the ability to combine data from actigraphs placed on both
      legs is also a significant barrier to their use in clinical settings. Further
      research is required to determine the optimal methods to quantify PLMS using leg
      actigraphy, as well as specific clinical situations in which these devices may
      prove most useful. 

PMID- 24726712
TI  - Brain magnetic resonance imaging of infants with bacterial meningitis.
AB  - OBJECTIVES: To describe the results of brain magnetic resonance imaging (MRI) of
      infants with bacterial meningitis and how the findings affected clinical
      management. STUDY DESIGN: This retrospective study included all infants <12
      months of age who were hospitalized at Children's Medical Center, Dallas and had
      culture-confirmed bacterial meningitis and a brain MRI from January 1, 2001 to
      December 1, 2011. Infants were identified by review of all positive bacterial
      cultures of cerebrospinal fluid (CSF) from the Children's Medical Center
      Microbiology Laboratory. Demographic, clinical, laboratory, and neuroimaging data
      were reviewed. Infants with ventriculoperitoneal shunt or whose CSF culture
      yielded skin commensals were excluded. A neuroradiologist blinded to clinical
      information reviewed all MRI studies. RESULTS: Of the 440 infants who had a
      positive CSF culture result, 111 (25%) had a pathogen isolated from CSF and were
      enrolled in the study. Of these, 68% (75/111) had a brain MRI performed during
      the hospitalization; abnormalities included leptomeningeal enhancement (57%),
      cerebral infarct (43%), subdural empyema (52%), cerebritis (26%), hydrocephalus
      (20%), and abscess (11%). By multiple logistic regression analysis, infants with
      late seizures and an abnormal neurologic examination were more likely to have an
      abnormal MRI (P < .05). MRI results led to neurosurgical intervention in 23% of
      infants; a positive bacterial culture of CSF obtained >48 hours after initiation
      of antibiotic therapy was associated with neurosurgical intervention (P = .01).
      Fourteen (19%) infants with bacterial meningitis had a normal brain MRI.
      CONCLUSIONS: Brain MRIs were performed frequently and often were abnormal in
      infants with bacterial meningitis, leading to changes in clinical management.

PMID- 24726713
TI  - Strategies for reducing unnecessary in-hospital formula supplementation and
      increasing rates of exclusive breastfeeding.

PMID- 24726714
TI  - Vulnerability in HIV prevention research with adolescents, reconsidered.

PMID- 24726715
TI  - Bioconversion of natural gas to liquid fuel: opportunities and challenges.
AB  - Natural gas is a mixture of low molecular weight hydrocarbon gases that can be
      generated from either fossil or anthropogenic resources. Although natural gas is
      used as a transportation fuel, constraints in storage, relatively low energy
      content (MJ/L), and delivery have limited widespread adoption. Advanced
      utilization of natural gas has been explored for biofuel production by
      microorganisms. In recent years, the aerobic bioconversion of natural gas (or
      primarily the methane content of natural gas) into liquid fuels (Bio-GTL) by
      biocatalysts (methanotrophs) has gained increasing attention as a promising
      alternative for drop-in biofuel production. Methanotrophic bacteria are capable
      of converting methane into microbial lipids, which can in turn be converted into
      renewable diesel via a hydrotreating process. In this paper, biodiversity,
      catalytic properties and key enzymes and pathways of these microbes are
      summarized. Bioprocess technologies are discussed based upon existing literature,
      including cultivation conditions, fermentation modes, bioreactor design, and
      lipid extraction and upgrading. This review also outlines the potential of Bio
      GTL using methane as an alternative carbon source as well as the major challenges
      and future research needs of microbial lipid accumulation derived from methane,
      key performance index, and techno-economic analysis. An analysis of raw material
      costs suggests that methane-derived diesel fuel has the potential to be
      competitive with petroleum-derived diesel. 

PMID- 24726716
TI  - Tight relationships between B lymphocytes and the skeletal system.
AB  - Mounting evidence indicates that the immune system and the skeletal system share
      several regulatory nodes. B lymphocytes, which play key roles in immune
      homeostasis, are uniquely endowed with osteointeractive properties. From their
      early development to the plasma cell stage, they are in close proximity with the
      skeletal system and produce factors important for bone maintenance. Not
      surprisingly, perturbation of B lymphopoiesis affects bone mass. Reciprocally,
      inactivation of bone cell functions results in B cell development blocks. This
      new understanding is refining our insights into the pathogenesis of several
      diseases such as periodontitis and rheumatoid arthritis. 

PMID- 24726717
TI  - Foreword-The 17th European Carbohydrate Symposium-EuroCarb17.

PMID- 24726718
TI  - Abadie's sign in adrenomyeloneuropathy.

PMID- 24726719
TI  - Acute-onset chronic inflammatory demyelinating polyneuropathy with focal
      segmental glomerulosclerosis.
AB  - Inflammatory neuropathies have been reported to occur in association with
      nephrotic syndrome. Their underlying immuno-pathogenic mechanisms remain unknown.
      A 50-year-old woman concurrently presented with acute-onset chronic inflammatory
      demyelinating polyneuropathy and nephrotic syndrome secondary to focal segmental
      glomerulosclerosis. Both neuropathy and proteinuria improved after plasma
      exchange and steroids. Literature review of cases of concurrent inflammatory
      neuropathies and nephrotic syndrome revealed similar neuro-renal presentations.
      This neuro-renal condition may be mediated by autoantibodies targeting myelin and
      podocytes. 

PMID- 24726720
TI  - Caspr2 antibody limbic encephalitis is associated with Hashimoto thyroiditis and
      thymoma.
AB  - BACKGROUND: Contactin-associated protein 2 (Caspr2) antibody is a neuronal
      surface antibody (NSAb) capable of causing disorders involving central and
      peripheral nervous systems (PNS). Thymoma can be found in patients with Caspr2
      antibodies and is most frequently associated with PNS symptoms. Myasthenia gravis
      can be found in these patients, but Hashimoto thyroiditis (HT) has not been
      reported. METHODS: A 76-year-old woman presented with sub-acute-onset changes in
      mental status. Further investigations revealed thymoma and HT. The presence of
      NSAb was tested by immunofluorescence on human embryonic kidney-293 cells.
      Treatment included corticosteroids, azathioprine, thyroxine, plasmapheresis, and
      thymectomy. RESULTS: Caspr2 antibody was positive in serum but absent in CSF.
      Brain magnetic resonance imaging (MRI) showed diffuse cortical atrophy, but did
      not change significantly after treatments. Brain positron emission tomography
      (PET) revealed diffuse hypometabolism over the cerebral cortex. The patient's
      mental status only partially improved. CONCLUSIONS: In Caspr2 antibody-associated
      syndromes, thymoma can occur in patients presenting only with LE, and HT can be
      an accompanying disease. Brain MRI and PET may not show specific lesions in
      limbic area. Patients with Caspr2 antibodies and thymoma may not have good
      prognosis.

PMID- 24726721
TI  - [It was not my usual visit (II). Neither was mine].

PMID- 24726722
TI  - Standardised packaging and tobacco-industry-funded research.

PMID- 24726724
TI  - Recent applications of fluorescence correlation spectroscopy in live systems.
AB  - Fluorescence correlation spectroscopy (FCS) is a widely used technique in
      biophysics and has helped address many questions in the life sciences. It
      provides important advantages compared to other fluorescence and biophysical
      methods. Its single molecule sensitivity allows measuring proteins within
      biological samples at physiological concentrations without the need of
      overexpression. It provides quantitative data on concentrations, diffusion
      coefficients, molecular transport and interactions even in live organisms. And
      its reliance on simple fluorescence intensity and its fluctuations makes it
      widely applicable. In this review we focus on applications of FCS in live
      samples, with an emphasis on work in the last 5 years, in the hope to provide an
      overview of the present capabilities of FCS to address biologically relevant
      questions.

PMID- 24726723
TI  - Elevated mitochondrial biogenesis in skeletal muscle is associated with
      testosterone-induced body weight loss in male mice.
AB  - Androgen reduces fat mass, although the underlying mechanisms are unknown. Here,
      we examined the effect of testosterone on heat production and mitochondrial
      biogenesis. Testosterone-treated mice exhibited elevated heat production.
      Treatment with testosterone increased the expression level of peroxisome
      proliferator-activated receptor-gamma coactivator-1alpha (PGC1alpha), ATP5B and
      Cox4 in skeletal muscle, but not that in brown adipose tissue and liver. mRNA
      levels of genes involved in mitochondrial biogenesis were elevated in skeletal
      muscle isolated from testosterone-treated male mice, but were down-regulated in
      androgen receptor deficient mice. These results demonstrated that the
      testosterone-induced increase in energy expenditure is derived from elevated
      mitochondrial biogenesis in skeletal muscle. 

PMID- 24726725
TI  - Wild type p53 reactivation: from lab bench to clinic.
AB  - The p53 tumor suppressor is the most frequently inactivated gene in cancer.
      Several mouse models have demonstrated that the reconstitution of the p53
      function suppresses the growth of established tumors. These facts, taken
      together, promote the idea of p53 reactivation as a strategy to combat cancer.
      This review will focus on recent advances in the development of small molecules
      which restore the function of wild type p53 by blocking its inhibitors Mdm2 and
      MdmX or their upstream regulators and discuss the impact of different p53
      functions for tumor prevention and tumor eradication. Finally, the recent
      progress in p53 research will be analyzed concerning the role of p53 cofactors
      and cellular environment in the biological response upon p53 reactivation and how
      this can be applied in clinic. 

PMID- 24726727
TI  - Protein arginine methyltransferase 7 has a novel homodimer-like structure formed
      by tandem repeats.
AB  - Protein arginine methyltransferase 7 (PRMT7) is a member of a family of enzymes
      that catalyze the transfer of methyl groups from S-adenosyl-l-methionine to
      nitrogen atoms on arginine residues. Here, we describe the crystal structure of
      Caenorhabditis elegans PRMT7 in complex with its reaction product S-adenosyl-L
      homocysteine. The structural data indicated that PRMT7 harbors two tandem
      repeated PRMT core domains that form a novel homodimer-like structure. S-adenosyl
      L-homocysteine bound to the N-terminal catalytic site only; the C-terminal
      catalytic site is occupied by a loop that inhibits cofactor binding. Mutagenesis
      demonstrated that only the N-terminal catalytic site of PRMT7 is responsible for
      cofactor binding.

PMID- 24726728
TI  - Mutant p53 exerts oncogenic effects through microRNAs and their target gene
      networks.
AB  - MicroRNAs are potent regulators of gene expression and modulate multiple cellular
      processes including proliferation, differentiation and apoptosis. A number of
      microRNAs have been shown to be regulated by p53, the most frequently mutated
      gene in human cancer. It is has been demonstrated that some mutant p53 proteins
      not only lose tumor suppressor activity, but also acquire novel oncogenic
      functions that are independent of wild-type p53. In this review, we highlight
      recent evidences suggesting that some mutant p53 proteins regulate the expression
      of specific microRNAs to gain oncogenic functions and identify a gene network
      regulated by the microRNAs downstream of mutant p53. 

PMID- 24726726
TI  - Molecular insights into NF2/Merlin tumor suppressor function.
AB  - The FERM domain protein Merlin, encoded by the NF2 tumor suppressor gene,
      regulates cell proliferation in response to adhesive signaling. The growth
      inhibitory function of Merlin is induced by intercellular adhesion and
      inactivated by joint integrin/receptor tyrosine kinase signaling. Merlin
      contributes to the formation of cell junctions in polarized tissues, activates
      anti-mitogenic signaling at tight-junctions, and inhibits oncogenic gene
      expression. Thus, inactivation of Merlin causes uncontrolled mitogenic signaling
      and tumorigenesis. Merlin's predominant tumor suppressive functions are
      attributable to its control of oncogenic gene expression through regulation of
      Hippo signaling. Notably, Merlin translocates to the nucleus where it directly
      inhibits the CRL4(DCAF1) E3 ubiquitin ligase, thereby suppressing inhibition of
      the Lats kinases. A dichotomy in NF2 function has emerged whereby Merlin acts at
      the cell cortex to organize cell junctions and propagate anti-mitogenic
      signaling, whereas it inhibits oncogenic gene expression through the inhibition
      of CRL4(DCAF1) and activation of Hippo signaling. The biochemical events
      underlying Merlin's normal function and tumor suppressive activity will be
      discussed in this Review, with emphasis on recent discoveries that have greatly
      influenced our understanding of Merlin biology. 

PMID- 24726729
TI  - Arginine methylation of the cellular nucleic acid binding protein does not affect
      its subcellular localization but impedes RNA binding.
AB  - Cellular nucleic acid binding protein (CNBP) contains seven zinc finger (ZF)
      repeats and an arginine and glycine (RG) rich sequence between the first and the
      second ZF. CNBP interacts with protein arginine methyltransferase PRMT1. Full
      length but not RG-deleted or mutated CNBP can be methylated. Treatment with a
      methylation inhibitor AdOx reduced CNBP methylation, but did not affect the
      concentrated nuclear localization of CNBP. Nevertheless, arginine methylation of
      CNBP appeared to interfere with its RNA binding activity. Our findings show that
      arginine methylation of CNBP in the RG motif did not change the subcellular
      localization, but regulated its RNA binding activity.

PMID- 24726730
TI  - Weak pulling forces exerted on Nin-orientated transmembrane segments during co
      translational insertion into the inner membrane of Escherichia coli.
AB  - Transmembrane helices (TMHs) in membrane proteins can be orientated with their N
      terminus towards the cytoplasm (Nin), or facing the non-cytoplasmic side (Nout).
      Most membrane proteins are inserted co-translationally into membranes, aided by
      Sec-type translocons. Since the final orientation of Nin- and Nout-orientated
      TMHs differs, they could also interact differently with the translocon and the
      surrounding membrane during insertion. We measured pulling forces exerted on Nin
      orientated TMHs during co-translational insertion into the inner membrane of
      Escherichia coli. Our results demonstrate that Nin-orientated TMHs experience a
      weaker pulling force but retain the overall biphasic force profile seen
      previously for Nout-orientated TMHs (Ismail et al., 2012 [1]). 

PMID- 24726731
TI  - The cytochrome c peroxidase and cytochrome c encounter complex: the other side of
      the story.
AB  - Formation of an encounter complex is important for efficient protein complex
      formation. The encounter state consists of an ensemble of orientations of two
      proteins in the complex. Experimental description of such ensembles inherently
      suffers from insufficient data availability. We have measured paramagnetic
      relaxation enhancements (PRE) on cytochrome c peroxidase (CcP) caused by its
      partner cytochrome c (Cc) carrying a spin label. The data complement earlier PRE
      data of spin labelled CcP, identifying several new interactions. This work
      demonstrates the need of obtaining as many independent data sets as possible to
      achieve the most accurate description of an encounter complex. 

PMID- 24726732
TI  - MIR146A inhibits JMJD3 expression and osteogenic differentiation in human
      mesenchymal stem cells.
AB  - Chromatin remodeling is important for cell differentiation. Histone
      methyltransferase EZH2 and histone demethylase JMJD3 (KDM6B) modulate levels of
      histone H3 lysine 27 trimethylation (H3K27me3). Interplay between the two
      modulators influence lineage specification in stem cells. Here, we identified
      microRNA MIR146A to be a negative regulator of JMJD3. In the osteogenic
      differentiation of human mesenchymal stem cells (hMSCs), we observed an
      upregulation of JMJD3 and a downregulation of MIR146A. Blocking JMJD3 activity in
      differentiating hMSCs reduced transcript levels of osteogenic gene RUNX2.
      H3K27me3 levels decreased at the RUNX2 promoter during cell differentiation.
      Modulation of MIR146A levels in hMSCs altered JMJD3 and RUNX2 expression and
      affected osteogenic differentiation. We conclude that JMJD3 promotes osteogenesis
      in differentiating hMSCs, with MIR146A regulating JMJD3. 

PMID- 24726733
TI  - High density of S100A9 positive inflammatory cells in prostate cancer stroma is
      associated with poor outcome.
AB  - PURPOSE: To elucidate if the density of inflammatory cells expressing S100A9 in
      malignant and surrounding non-malignant prostate tissues is a prognostic marker
      for outcome in prostate cancer patients. EXPERIMENTAL DESIGN: Tissue was obtained
      from 358 men diagnosed with prostate cancer at transurethral resection of the
      prostate due to obstructive voiding problems, of which 260 were then followed
      with watchful waiting. Tissue microarrays of both malignant and non-malignant
      tissues were stained with an antibody against S100A9. The number of stained
      inflammatory cells was scored and related to clinical outcome and
      histopathological parameters of known prognostic value. RESULTS: A high number of
      inflammatory cells expressing S100A9 in both malignant and surrounding non
      malignant tissues were associated with significantly shorter cancer-specific
      survival. This association remained significant when Gleason score and local
      tumour stage were analysed together with S100A9 in a Cox regression model. Low
      number of S100A9 positive cells in non-malignant stroma was correlated to
      significantly longer cancer-specific survival also in patients with Gleason score
      8-10 tumours. S100A9 positive cells in tumour stroma were correlated with Gleason
      score, hyaluronan, platelet-derived growth factor receptor beta (PDGFR-beta), and
      androgen receptor (inverse correlation) in tumour stroma. S100A9 positive cells
      in non-malignant stroma correlated with androgen receptor in this tissue
      compartment (inverse correlation). CONCLUSIONS: A high number of S100A9 positive
      inflammatory cells in tumour stroma and in non-malignant stroma were associated
      with shorter cancer-specific survival in prostate cancer patients.

PMID- 24726734
TI  - The components of progression as explanatory variables for overall survival in
      the Response Evaluation Criteria in Solid Tumours 1.1 database.
AB  - PURPOSE: Progressive disease (PD) per Response Evaluation Criteria in Solid
      Tumours (RECIST) 1.1 is defined as growth of measurable target lesions, presence
      of new lesions or unequivocal progression of non-target disease. In this
      manuscript we explored whether a more refined categorisation of tumour response
      and/or these components of progression, varying over time, can improve prediction
      of overall survival (OS) in the RECIST database. METHODS: Data were randomly
      selected from 13 randomised clinical trials (3758 patients with breast, lung or
      colorectal cancer). A maximum of five target lesions contributed to the sum of
      longest diameters. At each measurement time we determined: best target response
      as best % improvement from baseline; tumour growth of target lesions as worst %
      change and worst rate of increase (mm/week) from nadir; presence of new lesions
      and occurrence of non-target PD. OS was analysed by tumour type using Cox
      regression, adjusting for baseline sum and including these parameters as time
      dependent covariates. RESULTS: 36% of patients had new lesions, 28% non-target PD
      and 49% experienced target lesion growth (median strongest growth 1.5mm/week).
      Regardless of tumour type, presence of new lesions (hazard ratio (HR) ranging 1.5
      2.3) and non-target PD (HR 1.5-2.0) were strongly associated with worse OS. The
      explanatory value of tumour growth for OS was low compared to the other
      components. CONCLUSION: Modelling target lesion tumour growth did not show a
      marked improvement in OS prediction over and above the other components. These
      analyses enable a better understanding of the role of each component in PD
      evaluation. Work is ongoing to incorporate this information into an updated
      version of RECIST with enhanced prediction of subsequent survival.

PMID- 24726736
TI  - Falsely elevated chloride during treatment with sodium thiosulfate.

PMID- 24726735
TI  - Completeness and registration bias in PROCARE, a Belgian multidisciplinary
      project on cancer of the rectum with participation on a voluntary basis.
AB  - BACKGROUND: PROCARE, a Belgian multidisciplinary project on rectal cancer,
      started in 2006 with participation on a voluntary basis. Completeness and bias of
      registration in PROCARE were assessed. METHODS: Data from 6353 patients with
      rectal cancer were extracted from the population based Belgian Cancer Registry
      for the period 2006-2008. Registration bias was studied by comparing patient,
      tumour and treatment characteristics of cases registered and non-registered in
      PROCARE. Relative survival (RS) of patient subgroups was analysed. RESULTS:
      PROCARE included 37% of all Belgian rectal cancer patients. Registration was
      highly variable between participating centres which recorded on average 56% of
      their patients. Significant differences in patient, tumour and treatment related
      characteristics were observed between registered and non-registered patients. The
      5-year RS was 77% (95% confidence interval (CI): 74-80%) for registered patients
      and 56% (95% CI: 53-59%) for non-registered patients. After adjustment for
      patient, tumour characteristics and volume of centre, the relative excess risk of
      dying (RER) between registered and non-registered patients was 2.15 (95% CI: 1.85
      2.50, p<0.001). The 5-year RS of patients treated in centres that never
      participated in the project was 59% (95% CI: 55-63%) and, after adjustment, the
      RER was 1.16 (95% CI: 1.00-1.35, p<0.050) compared to patients of the
      participating centres. CONCLUSION: Registration of PROCARE patient data was
      incomplete, biased and variable between centres. Participation on a voluntary
      basis should be avoided for further projects. Quality assurance on a centre level
      requires compulsory and complete registration with a minimal but relevant data
      set for all patients treated in all centres.

PMID- 24726737
TI  - Recombinant BCG coexpressing Ag85B, ESAT-6 and Rv3620c elicits specific Th1
      immune responses in C57BL/6 mice.
AB  - Tuberculosis (TB) remains to be an enormous global health problem. The
      inconsistent protection efficacy of Bacille Calmette-Guerin (BCG) calls for new
      vaccines for TB. One choice to improve the efficacy of BCG vaccine is recombinant
      BCG (rBCG). Experimental evidences have revealed that Ag85B, ESAT-6 and Rv3620c
      are important immunodominant antigens of Mycobacterium tuberculosis. In this
      study, we have constructed a novel rBCG expressing fusion protein Ag85B-ESAT6
      Rv3620c and evaluated the immunogenicity of this rBCG in C57BL/6 mice. Results
      show that there is a strong TB-specific CD4(+) and CD8(+) T lymphocytes
      proliferation in mice immunized with this rBCG vaccine. A single dose
      immunization of rBCG could induce a significantly strong Th1 immune response
      characterized by an increasing ratio of antigen-specific IgG2b/IgG1 as well as a
      high expression level of Th1 cytokines such as IFN-gamma, TNF-alpha and IL-2.
      This conclusion was confirmed by a decreased secretion of Th2 cytokine IL-10.
      Moreover, this rBCG induced a strong humoral response in mice with an increasing
      antigen-specific IgG titer. Therefore, we concluded that this rBCG could
      significantly increase both Th1 type cellular immune response and antigen
      specific humoral response compared with BCG. The above observations demonstrated
      that rBCG::Ag85B-ESAT6-Rv3620c is a potential candidate vaccine against M.
      tuberculosis for further study. 

PMID- 24726738
TI  - Reversal, maintenance or progression: what happens to the liver after a virologic
      cure of hepatitis C?
AB  - A sustained virological response (SVR) from HCV (synonymous with virological
      cure) leads to decreased mortality, morbidity and improved quality of life, as
      well as a reduced incidence of liver disease progression, including liver
      failure, cirrhosis and hepatocellular carcinoma. Large clinical trials comparing
      pre- and post-treatment liver biopsies demonstrate improvements in inflammation
      as well as fibrosis score following SVR. However, a small subset of patients
      display persistent hepatic inflammation and/or progress to cirrhosis despite SVR.
      In addition to conferring a risk of fibrosis progression, advanced fibrosis pre
      treatment is a major risk factor for post-SVR hepatocellular carcinoma. In this
      review, we discuss the mechanisms of fibrosis regression uncovered using
      experimental fibrosis models and highlight potential mechanisms in those few
      patients with fibrosis progression despite SVR. We also introduce current
      concepts of fibrosis-dependent tumorigenesis post-SVR in patients with advanced
      disease. This article forms part of a symposium in Antiviral Research on
      "Hepatitis C: next steps toward global eradication." 

PMID- 24726740
TI  - Patients at elevated risk of melanoma: individual predictors of non-compliance to
      GP referral for a dermatologist consultation.
AB  - OBJECTIVE: The aim of this study is to assess whether patients at elevated risk
      of melanoma attended a dermatologist consultation after a General Practitioner
      referral and to determine individual predictors of non-compliance. METHOD: This
      survey included 1506 high-risk French patients (selected using the Self
      Assessment Melanoma Risk Score) referred to a dermatologist between April and
      October 2011. Compliance was evaluated from January to April 2012, based on
      attendance at a dermatologist consultation (or scheduling an appointment).
      Demographic data and factors mapping the Health Belief Model were tested as
      correlates using a multivariate logistic regression. RESULTS: Compliance with
      referral was 58.4%. The top seven factors associated with non-compliance were as
      follows: GP advice to consult was unclear (OR=13.22; [7.66-23.56]); no previous
      participation in cancer screenings, including smear tests (OR=5.03; [2.23-11.83])
      and prostate screening (OR=2.04; [1.06-3.97]); lack of knowledge that melanoma
      was a type of cancer (OR=1.94; [1.29-2.92]); and reporting no time to make an
      appointment (OR=2.08; [1.82-2.38]), forgetting to make an appointment (OR=1.26;
      [1.08-1.46]), long delays in accessing an appointment (OR=1.25; [1.12-1.41]), not
      being afraid of detecting something abnormal (OR=1.54; [1.35-1.78]), no need to
      consult a dermatologist to feel secure (OR=1.28; [1.09-1.51]). CONCLUSION:
      Physicians should be aware of the factors predicting patient compliance with
      referrals for dermatologist consultations; better General Practitioner counseling
      might enhance compliance in high-risk populations.

PMID- 24726739
TI  - Linsitinib (OSI-906) antagonizes ATP-binding cassette subfamily G member 2 and
      subfamily C member 10-mediated drug resistance.
AB  - In this study we investigated the effect of linsitinib on the reversal of
      multidrug resistance (MDR) mediated by the overexpression of the ATP-binding
      cassette (ABC) subfamily members ABCB1, ABCG2, ABCC1 and ABCC10. Our results
      indicate for the first time that linsitinib significantly potentiate the effect
      of anti-neoplastic drugs mitoxantrone (MX) and SN-38 in ABCG2-overexpressing
      cells; paclitaxel, docetaxel and vinblastine in ABCC10-overexpressing cells.
      Linsitinib moderately enhanced the cytotoxicity of vincristine in cell lines
      overexpressing ABCB1, whereas it did not alter the cytotoxicity of substrates of
      ABCC1. Furthermore, linsitinib significantly increased the intracellular
      accumulation and decreased the efflux of [(3)H]-MX in ABCG2-overexpressing cells
      and [(3)H]-paclitaxel in ABCC10-overexpressing cells. However, linsitinib, at a
      concentration that reversed MDR, did not significantly alter the expression
      levels of either the ABCG2 or ABCC10 transporter proteins. Furthermore,
      linsitinib did not significantly alter the intracellular localization of ABCG2 or
      ABCC10. Moreover, linsitinib stimulated the ATPase activity of ABCG2 in a
      concentration-dependent manner. Overall, our study suggests that linsitinib
      attenuates ABCG2- and ABCC10-mediated MDR by directly inhibiting their function
      as opposed to altering ABCG2 or ABCC10 protein expression. 

PMID- 24726742
TI  - Sex differences in early outcomes after lung cancer resection: analysis of the
      Society of Thoracic Surgeons General Thoracic Database.
AB  - OBJECTIVES: Women with lung cancer have superior long-term survival outcomes
      compared with men, independent of stage. The cause of this disparity is unknown.
      For patients undergoing lung cancer resection, these survival differences could
      be due, in part, to relatively better perioperative outcomes for women. This
      study was undertaken to determine differences in perioperative outcomes after
      lung cancer surgery on the basis of sex. METHODS: The Society of Thoracic
      Surgeons' General Thoracic Database was queried for all patients undergoing
      resection of lung cancer between 2002 and 2010. Postoperative complications were
      analyzed with respect to sex. Univariable analysis was performed, followed by
      multivariable modeling to determine significant risk factors for postoperative
      morbidity and mortality. RESULTS: A total of 34,188 patients (16,643 men and
      17,545 women) were considered. Univariable analysis demonstrated statistically
      significant differences in postoperative complications favoring women in all
      categories of postoperative complications. Women also had lower in-hospital and
      30-day mortality (odds ratio, 0.56; 95% confidence interval, 0.44-0.71; P <
      .001). Multivariable analysis demonstrated that several preoperative conditions
      independently predicted 30-day mortality: male sex, increasing age, lower
      diffusion capacity, renal insufficiency, preoperative radiation therapy, cancer
      stage, extent of resection, and thoracotomy as surgical approach. Coronary artery
      disease was an independent predictor of mortality in women but not in men.
      Thoracotomy as the surgical approach and preoperative radiation therapy were
      predictive of mortality for men but not for women. Postoperative prolonged air
      leak and empyema predicted mortality in men but not in women. CONCLUSIONS: Women
      have lower postoperative morbidity and mortality after lung cancer surgery. Some
      risk factors are sex-specific with regard to mortality. Further study is
      warranted to determine the cause of these differences and to determine their
      effect on survival.

PMID- 24726741
TI  - The monocyte-macrophage axis in the intestine.
AB  - Macrophages are one of the most abundant leucocytes in the intestinal mucosa
      where they are essential for maintaining homeostasis. However, they are also
      implicated in the pathogenesis of disorders such as inflammatory bowel disease
      (IBD), offering potential targets for novel therapies. Here we discuss the
      function of intestinal monocytes and macrophages during homeostasis and describe
      how these populations and their functions change during infection and
      inflammation. Furthermore, we review the current evidence that the intestinal
      macrophage pool requires continual renewal from circulating blood monocytes,
      unlike most other tissue macrophages which appear to derive from primitive
      precursors that subsequently self-renew. 

PMID- 24726743
TI  - Transapical JenaValve in a degenerated Freedom SOLO bioprosthesis.

PMID- 24726744
TI  - Malignant pleural mesothelioma and the Society of Thoracic Surgeons Database: an
      analysis of surgical morbidity and mortality.
AB  - BACKGROUND: To date, reported surgical morbidity and mortality for
      pleurectomy/decortication and extrapleural pneumonectomy performed for malignant
      pleural mesothelioma primarily represent the experience of a few specialized
      centers. For comparison, we examined early outcomes of pleurectomy/decortication
      and extrapleural pneumonectomy from a broader group of centers/surgeons
      participating in the Society of Thoracic Surgeons-General Thoracic Database.
      METHODS: All patients in the Society of Thoracic Surgeons-General Thoracic
      Database (version 2.081, representing 2009-2011) who underwent
      pleurectomy/decortication or extrapleural pneumonectomy for malignant pleural
      mesothelioma were identified. Patient characteristics, morbidity, mortality,
      center volume, and procedure were examined using univariable and multivariable
      analyses. RESULTS: A total of 225 patients underwent pleurectomy/decortication (n
      = 130) or extrapleural pneumonectomy (n = 95) for malignant pleural mesothelioma
      at 48 centers. Higher volumes of procedures (>=5/y) were performed at 3
      pleurectomy/decortication and 2 extrapleural pneumonectomy centers. Patient
      characteristics were statistically equivalent between pleurectomy/decortication
      and extrapleural pneumonectomy groups, except those undergoing extrapleural
      pneumonectomy were younger (63.2 +/- 7.8 years vs 68.3 +/- 9.5 years; P < .001)
      and more likely to have received preoperative chemotherapy (30.1% vs 17.8%; P =
      .036). Major morbidity was greater after extrapleural pneumonectomy, including
      acute respiratory distress syndrome (8.4% vs 0.8%; P = .005), reintubation (14.7%
      vs 2.3%; P = .001), unexpected reoperation (9.5% vs 1.5%; P = .01), and sepsis
      (4.2% vs 0%; P = .03), as was mortality (10.5% vs 3.1%; P = .03). Multivariate
      analyses revealed that extrapleural pneumonectomy was an independent predictor of
      major morbidity or mortality (odds ratio, 6.51; P = .001). Compared with high
      volume centers, increased acute respiratory distress syndrome was seen in low
      volume centers performing extrapleural pneumonectomy (0% vs 12.5%; P = .05).
      CONCLUSIONS: Extrapleural pneumonectomy is associated with greater morbidity and
      mortality compared with pleurectomy/decortication when performed by participating
      surgeons of the Society of Thoracic Surgeons-General Thoracic Database. Effects
      of center volume require further study.

PMID- 24726745
TI  - Right hemicolectomy plus pancreaticoduodenectomy vs partial duodenectomy in
      treatment of locally advanced right colon cancer invading pancreas and/or only
      duodenum.
AB  - INTRODUCTION: Pancreatic or duodenal invasion by locally advanced right colon
      cancer is an unusual event whose management still represents a surgical
      challenge. This review aims to compare results of limited vs. extended resection
      in case of primary right colon cancer invading pancreas and/or duodenum. METHODS:
      A systematic search in Medline, Embase and Cochrane Central Register of
      Controlled Trials (CENTRAL) was performed. All trials describing the surgical
      treatment of right colon cancer invading pancreas and/or duodenum were
      considered. A data extraction sheet was developed, based on the Cochrane
      Consumers and Communication Review Group's data extraction template. RESULTS: 5
      years overall survival was 52% after en bloc pancreaticoduodenectomy plus right
      hemicolectomy vs. 0 and 25% in case of duodenal resection with correction by
      direct suture or pedicled ileal flap, respectively. 30-day postoperative
      morbidity rate was slightly higher after en block resections (12.8%) with respect
      to duodenal local resection and direct suture or pedicled ileal flap repair (0
      and 12.2%, respectively). After extended resection the rate of pancreatico
      jejunal anastomotic leakage was 7.7%. CONCLUSIONS: In patients with right colon
      cancer extended to the pancreas and/or duodenum surgical multivisceral resection
      is suggested when complete tumour removal (R0) is achievable. Even though no
      significant differences in postoperative morbidity and mortality have been shown,
      5 y OS has improved in extended resections as compared to duodenal local
      resection with defect repair either by direct suture or by a pedicled ileal flap.

PMID- 24726746
TI  - Effect of biodegradability on CXCR4 antagonism, transfection efficacy and
      antimetastatic activity of polymeric Plerixafor.
AB  - Chemokine receptor CXCR4 and its sole ligand SDF-1 are key players in regulating
      cancer cell invasion and metastasis. Plerixafor (AMD3100) is a small-molecule
      CXCR4 antagonist that prevents binding of SDF-1 to CXCR4 and has potential in
      prevention of cancer metastasis. This study investigates the influence of
      biodegradability of a recently reported polymeric Plerixafor (PAMD) on CXCR4
      antagonism, antimetastatic activity, and transfection efficacy of PAMD polyplexes
      with plasmid DNA. We show that PAMD exhibits CXCR4 antagonism and inhibition of
      cancer cell invasion in vitro regardless of its biodegradability. Biodegradable
      PAMD showed considerably enhanced transfection efficiency and decreased
      cytotoxicity when compared with the non-degradable PAMD. Despite similar CXCR4
      antagonism in vitro, only biodegradable PAMD displayed antimetastatic activity in
      experimental lung metastasis model in vivo. 

PMID- 24726747
TI  - Combined mTOR inhibitor rapamycin and doxorubicin-loaded cyclic octapeptide
      modified liposomes for targeting integrin alpha3 in triple-negative breast
      cancer.
AB  - A novel therapeutic strategy combining mTOR inhibitor rapamycin (RAPA) and
      doxorubicin (DOX)-loaded cyclic octapeptide liposomes for targeting integrin
      alpha3 was expected to combat the triple-negative breast cancer (TNBC). RAPA was
      loaded into PEG-PCL polymer micelles (M-RAPA) to realize solubilization. Flow
      cytometry analysis and laser confocal microscopy were used to evaluate the in
      vitro cellular uptake. The in vivo tumor targeting and bio-distribution were
      investigated by living fluorescence imaging. As the results, LXY modification
      significantly enhanced the cellular uptake of liposomal DOX in integrin alpha3
      overexpressed TNBC cells (MDA-MB-231) in vitro and accordingly improved the tumor
      accumulation of liposomes in vivo. When used alone or in combination with LXY-LS
      DOX, M-RAPA could greatly inhibit the expression of HIF-1alpha protein, which is
      always highly expressed in malignant cancers and involved in tumor angiogenesis,
      proliferation, therapeutic resistance and poor prognosis. Meanwhile, the improved
      efficacy of combined targeted therapy with LXY-LS-DOX and M-RAPA was demonstrated
      by the in vitro cytotoxicity against model TNBC cells and in vivo anti-tumor
      activity against mouse bearing TNBC model. These results suggested that the
      targeted combinational therapy based on LXY-LS-DOX and M-RAPA systems may provide
      a rational strategy to improve therapeutic outcomes of TNBC. 

PMID- 24726748
TI  - Label-free dendrimer-like silica nanohybrids for traceable and controlled gene
      delivery.
AB  - To create advanced functional nanocarriers for achieving excellent gene delivery
      performance, fluorescence label-free hybridized dendrimer-like silica
      nanocarriers (HPSNs-AC-PEI) were developed by using the endosomal pH and
      cytoplasmic glutathione (GSH) responsive autofluorescent acetaldehyde-modified
      cystine (AC) to link non-toxic low molecular weight branched polyethyleneimine
      (PEI) onto amino-functionalized dendrimer-like silica nanoparticles with
      hierarchical pores (HPSNs-NH2). The specific microstructure of this hybridized
      nanocarrier makes it not only show low cytotoxicity and high gene loading
      capability, but also display high gene transfection efficiency. The cleavage of
      disulfide bonds caused by GSH facilitates plasmid DNA (pDNA) release. Moreover,
      the pH and GSH controlled gene delivery profile can be real-time tracked using
      the autofluorescence of HPSNs-AC-PEI. 

PMID- 24726749
TI  - Multifunctional liposomes loaded with paclitaxel and artemether for treatment of
      invasive brain glioma.
AB  - Invasive brain glioma is the most lethal type of cancer and is highly
      infiltrating. This leads to an extremely poor prognosis and makes complete
      surgical removal of the tumor virtually impossible. Non-penetration of
      therapeutic drugs across the blood-brain barrier (BBB), brain cancer stem cells
      (CSCs), and brain cancer vasculogenic mimicry (VM) results in relapse after
      surgical and radio therapy. We developed a functional targeting chemotherapy for
      transporting drugs across the BBB, destroying VM channels, and eliminating CSCs
      and cancer cells in the brain. The studies were undertaken on brain glioma cells
      in vitro and in brain glioma-bearing rats. Using paclitaxel as the anticancer
      drug and artemether as the regulator of apoptosis and inhibitor of VM channels, a
      kind of functional targeting paclitaxel plus artemether liposomes was developed
      by modifying two new functional materials: a mannose-vitamin E derivative
      conjugate (MAN-TPGS1000) and a dequalinium-lipid derivative conjugate (DQA
      PEG2000-DSPE). The transport mechanism across the BBB was associated with
      receptor-mediated endocytosis by MAN-TPGS1000 conjugate via glucose transporters
      and adsorptive-mediated endocytosis by DQA-PEG2000-DSPE conjugate via electric
      charge-based interactions. The efficacy was related to the destruction of VM
      channels by regulating VM indicators, as well as the induction of apoptosis in
      brain cancer cells and CSCs by activating apoptotic enzymes and pro-apoptotic
      proteins and inhibiting anti-apoptotic proteins. These data suggest that the
      chemotherapy using functional targeting paclitaxel plus artemether liposomes
      could provide a new strategy for treating invasive brain glioma. 

PMID- 24726750
TI  - Spontaneous intramedullary hematoma initially mimicking myocardial infarction.
AB  - Spontaneous intramedullary hematoma (IMH) is a rare condition. The initial
      clinical manifestations are variable. Early symptoms of high thoracic IMH include
      thoracocervical pain that can be mistaken for emergent cardiopulmonary conditions
      such as myocardial infarction, pulmonary embolus, and aortic dissection. We
      report on a 34-year-old man who presented initially with chest pain and radiating
      pain in both shoulders. He was initially misdiagnosed as having a myocardial
      infarction and treated with heparin. Two hours after admission, correct diagnosis
      of IMH was based on the repeated neurologic examination and spine magnetic
      resonance imaging study. The patient underwent emergency surgical decompression
      and hematoma removal.We draw the misdiagnosis to the attention of the emergency
      physicians because early recognition of spontaneous IMH is very important for
      early surgical decompression to improve the prognosis.

PMID- 24726751
TI  - Descriptive epidemiology of cancer of unknown primary site in Scotland, 1961
      2010.
AB  - BACKGROUND: Cancers of unknown primary site (CUP) pose problems for diagnosis,
      treatment, and accurate prediction of prognosis. However, there are limited
      published data describing the epidemiology of this disease entity. Our aim was to
      describe the epidemiology of CUP in Scotland. METHODS: Anonymised data, covering
      the period 1961-2010, were extracted from the Scottish Cancer Registry database,
      based on the following ICD-10 diagnostic codes: C26.0, C26.8, C26.9, C39, and C76
      C80. Age-standardised incidence rates were calculated by direct standardisation
      to the World Standard Population. Estimates of observed survival were calculated
      by the Kaplan-Meier method. RESULTS: Between 1961 and 2010, there were 50,941
      registrations of CUP, representing 3.9% of all registrations of invasive cancers.
      Age-standardised rates increased to a peak in the early to mid-1990s, followed by
      a steeper decrease in rates. During 2001-2010, age-standardised rates of CUP were
      higher in the most compared with the least deprived fifth of the population.
      Observed survival was marginally higher in patients diagnosed during 2001-2010
      (median 5.6 weeks) compared with those diagnosed in the previous two decades.
      During the most recent decade, survival decreased with age at diagnosis, and was
      higher in patients with squamous cell carcinoma and with lymph node metastases.
      CONCLUSION: Patterns of CUP in Scotland are largely consistent with those
      reported from the few other countries that have published data. However, in
      comparing studies, it is important to note that there is heterogeneity in terms
      of definition of CUP, as well as calendar period of diagnosis or death. Variation
      in the definition of CUP between different epidemiological studies suggests that
      there would be merit in seeking international agreement on guidelines for the
      registration of CUP as well as a standard grouping of diagnostic codes for
      analysis.

PMID- 24726752
TI  - A large scale (N=102) functional neuroimaging study of error processing in a
      Go/NoGo task.
AB  - We report a functional magnetic resonance imaging (fMRI) study of 102 healthy
      participants who completed a demanding Go/NoGo task. The primary purpose of this
      study was to delineate the neural systems underlying responses to errors in a
      large sample. We identified a number of regions engaged during error processing
      including the anterior cingulate, left lateral prefrontal areas and bilateral
      inferior frontal gyrus, and the subthalamic nucleus. The power afforded by the
      large cohort enabled identification of regions not consistently measured during
      Go/NoGo tasks thus helping to incrementally refine our understanding of the
      neural correlates of error processing. With the present fMRI results, in
      combination with our previous exploration of response inhibition (Steele et al.),
      we outline a comprehensive set of regions associated with both response
      inhibition and error processing. 

PMID- 24726753
TI  - Sox2 promotes malignancy in glioblastoma by regulating plasticity and astrocytic
      differentiation.
AB  - The high-mobility group-box transcription factor sex-determining region Y-box 2
      (Sox2) is essential for the maintenance of stem cells from early development to
      adult tissues. Sox2 can reprogram differentiated cells into pluripotent cells in
      concert with other factors and is overexpressed in various cancers. In
      glioblastoma (GBM), Sox2 is a marker of cancer stemlike cells (CSCs) in
      neurosphere cultures and is associated with the proneural molecular subtype.
      Here, we report that Sox2 expression pattern in GBM tumors and patient-derived
      mouse xenografts is not restricted to a small percentage of cells and is
      coexpressed with various lineage markers, suggesting that its expression extends
      beyond CSCs to encompass more differentiated neoplastic cells across molecular
      subtypes. Employing a CSC derived from a patient with GBM and isogenic
      differentiated cell model, we show that Sox2 knockdown in the differentiated
      state abolished dedifferentiation and acquisition of CSC phenotype. Furthermore,
      Sox2 deficiency specifically impaired the astrocytic component of a biphasic
      gliosarcoma xenograft model while allowing the formation of tumors with
      sarcomatous phenotype. The expression of genes associated with stem cells and
      malignancy were commonly downregulated in both CSCs and serum-differentiated
      cells on Sox2 knockdown. Genes previously shown to be associated with
      pluripontency and CSCs were only affected in the CSC state, whereas embryonic
      stem cell self-renewal genes and cytokine signaling were downregulated, and the
      Wnt pathway activated in differentiated Sox2-deficient cells. Our results
      indicate that Sox2 regulates the expression of key genes and pathways involved in
      GBM malignancy, in both cancer stemlike and differentiated cells, and maintains
      plasticity for bidirectional conversion between the two states, with significant
      clinical implications. 

PMID- 24726754
TI  - Loss of CD28 expression by liver-infiltrating T cells contributes to pathogenesis
      of primary sclerosing cholangitis.
AB  - BACKGROUND & AIMS: T-cell-mediated biliary injury is a feature of primary
      sclerosing cholangitis (PSC). We studied the roles of CD28(-) T cells in PSC and
      their regulation by vitamin D. METHODS: Peripheral and liver-infiltrating
      mononuclear cells were isolated from blood or fresh liver tissue. We analyzed
      numbers, phenotypes, functions, and localization patterns of CD28(-) T cells,
      along with their ability to activate biliary epithelial cells. We measured levels
      of tumor necrosis factor (TNF)alpha in liver tissues from patients with PSC and
      the effects of exposure to active vitamin D (1,25[OH]2D3) on expression of CD28.
      RESULTS: A significantly greater proportion of CD4(+) and CD8(+) T cells that
      infiltrated liver tissues of patients with PSC were CD28(-), compared with
      control liver tissue (CD4(+): 30.3% vs 2.5%, P < .0001; and CD8(+): 68.5% vs
      31.9%, P < .05). The mean percentage of CD4(+)CD28(-) T cells in liver tissues
      from patients with PSC was significantly higher than from patients with primary
      biliary cirrhosis or nonalcoholic steatohepatitis (P < .05). CD28(-) T cells were
      activated CD69(+)CD45RA(-) C-C chemokine receptor (CCR)7(-) effector memory and
      perforin(+) granzyme B(+) cytotoxic cells, which express CD11a, CX3CR1, C-X3-C
      motif receptor 6 (CXCR6), and CCR10-consistent with their infiltration of liver
      and localization around bile ducts. Compared with CD28(+) T cells, activated
      CD28(-) T cells produced significantly higher levels of interferon gamma and
      TNFalpha (P < .05), and induced up-regulation of intercellular cell adhesion
      molecule-1, HLA-DR, and CD40 by primary epithelial cells (3.6-fold, 1.5-fold, and
      1.2-fold, respectively). Liver tissue from patients with PSC contained high
      levels of TNFalpha; TNFalpha down-regulated the expression of CD28 by T cells in
      vitro (P < .01); this effect was prevented by administration of 1,25(OH)2D3 (P <
      .05). CONCLUSIONS: Inflammatory CD28(-) T cells accumulate in livers of patients
      with PSC and localize around bile ducts. The TNFalpha-rich microenvironment of
      this tissue promotes inflammation; these effects are reversed by vitamin D in
      vitro.

PMID- 24726755
TI  - Loss of syntaxin 3 causes variant microvillus inclusion disease.
AB  - Microvillus inclusion disease (MVID) is a disorder of intestinal epithelial
      differentiation characterized by life-threatening intractable diarrhea. MVID can
      be diagnosed based on loss of microvilli, microvillus inclusions, and
      accumulation of subapical vesicles. Most patients with MVID have mutations in
      myosin Vb that cause defects in recycling of apical vesicles. Whole-exome
      sequencing of DNA from patients with variant MVID showed homozygous truncating
      mutations in syntaxin 3 (STX3). STX3 is an apical receptor involved in membrane
      fusion of apical vesicles in enterocytes. Patient-derived organoid cultures and
      overexpression of truncated STX3 in Caco-2 cells recapitulated most
      characteristics of variant MVID. We conclude that loss of STX3 function causes
      variant MVID. 

PMID- 24726756
TI  - Risk of osteoarthritis secondary to partial or total arthrodesis of the subtalar
      and midtarsal joints after a minimum follow-up of 10 years.
AB  - INTRODUCTION: The goal of this retrospective, multicentre study was to evaluate
      the long-term outcomes in patients who have undergone partial or total
      arthrodesis of the subtalar and midtarsal joints. HYPOTHESIS: Secondary
      osteoarthritis of the adjacent joints can negatively affect the outcomes more
      than 10 years after these fusion procedures. MATERIAL AND METHODS: The outcomes
      of 72 fusions (total: 22; partial: 50) performed between 1981 and 2002 were
      evaluated using the Maryland Foot Score (MFS), self-evaluation questionnaire and
      three weight-bearing X-ray views (Meary's with cerclage wire around heel, lateral
      and dorsoplantar). The average follow-up was 15 +/- 5 years (range 10-31).
      RESULTS: There were two deep infections that resolved after lavage and
      antibiotics therapy. There were 21 early complications (10 complex regional pain
      syndrome, 7 delayed wound healing, 2 superficial infections, 2 venous thrombosis)
      that all resolved. There were five cases of non-union (6.9%) that healed after
      being re-operated. After five years, secondary osteoarthritis led to the fusion
      being extended to the tibotalar joint (1 case) and midtarsal joint (1 case). At
      the last follow-up, the average MFS was 71.5 (range 25-100). Patient deemed the
      result as either excellent (10%), very good (9%), good (55%), poor (19%) or bad
      (7%). Pain at the last follow-up was present in 84% of cases. The rear-foot was
      normally aligned in 45% of cases, varus aligned in 22% and valgus aligned in 33%.
      The MFS was significantly better in patients with normal alignment. Patients with
      neurological foot disorders had significantly more preoperative (80% cavovarus)
      and postoperative foot deformity (P<0.05). At the last follow-up, the rate of
      secondary osteoarthritis in the surrounding joints was elevated: 73% tibiotalar,
      58.3% subtalar, 65.8% talonavicular, 53.5% calaneocuboid. The presence of
      osteoarthritis was not correlated with pain or lower MFS. However there was
      significantly more pain at last follow-up than at 12 months postoperative and two
      fusions were required in patients with secondary osteoarthritis. CONCLUSION:
      Although partial or total arthrodesis of the subtalar and midtarsal joints is a
      reliable procedure, it induces secondary osteoarthritis. Even though it seems to
      be well tolerated more than 10 years after the initial procedure, this
      possibility must be discussed with young, active patients. LEVEL OF EVIDENCE: IV,
      retrospective study.

PMID- 24726757
TI  - Diversity of immunoglobulin lambda light chain gene usage over developmental
      stages in the horse.
AB  - To further studies of neonatal immune responses to pathogens and vaccination, we
      investigated the dynamics of B lymphocyte development and immunoglobulin (Ig)
      gene diversity. Previously we demonstrated that equine fetal Ig VDJ sequences
      exhibit combinatorial and junctional diversity levels comparable to those of
      adult Ig VDJ sequences. Herein, RACE clones from fetal, neonatal, foal, and adult
      lymphoid tissue were assessed for Ig lambda light chain combinatorial,
      junctional, and sequence diversity. Remarkably, more lambda variable genes (IGLV)
      were used during fetal life than later stages and IGLV gene usage differed
      significantly with time, in contrast to the Ig heavy chain. Junctional diversity
      measured by CDR3L length was constant over time. Comparison of Ig lambda
      transcripts to germline revealed significant increases in nucleotide diversity
      over time, even during fetal life. These results suggest that the Ig lambda light
      chain provides an additional dimension of diversity to the equine Ig repertoire. 

PMID- 24726758
TI  - Urinary concentrations of acrylamide (AA) and N-acetyl-S-(2-carbamoylethyl)
      cysteine (AAMA) and associations with demographic factors in the South Korean
      population.
AB  - Acrylamide (AA) and N-acetyl-S-(2-carbamoylethyl)-cysteine (AAMA) are important
      urinary biomarkers of acrylamide exposure in human biomonitoring, because AA is
      classified as a probable carcinogen in humans. In this study, urinary AA and AAMA
      were assessed in the South Korean adult population aged 18-69, based on the
      Korean National Human Biomonitoring Survey conducted in 2009. Urinary metabolites
      in samples were analyzed with LC-MS/MS system. Relying on data from 1873
      representative South Korean adults, the population-weighted geometric means of
      urinary AA and AAMA concentrations were 6.8 ng/ml (95% CI: 6.4-7.3), and 30.0
      ng/ml (95% confidence interval (CI): 28.2-31.8), respectively. The creatinine
      adjusted geometric means of AA and AAMA were 6.2 MUg/g creatinine (95% CI: 5.8
      6.7) and 26.4MUg/g creatinine (95% CI: 24.9-28.0), respectively. When covariates
      for predictors of urinary metabolites were adjusted simultaneously in a log
      linear multiple regressions, the strongest predictors of urinary AA were
      education (OR=1.08-1.28; 95% CI: 1.11-1.48; p=0.0024) and age (OR=0.66-0.84; 95%
      CI: 0.54-0.97; p=0.0003), and those of urinary AAMA were smoking status (OR=1.16
      2.63; 95% CI: 0.98-3.08; p=0.001) and education (OR=1.12-1.19; 95% CI: 1.02-1.38;
      p=0.0425). The ratio of current/never smokers for urinary AA was 1.3, whereas the
      same ratio for urinary AAMA was 3.0. These findings suggested that most South
      Koreans had detectable levels of AA and AAMA (98.7% and 99.4%, respectively) in
      their urine and that the body burden of AA and AAMA varied according to
      demographic, geographic, and lifestyle (smoking) factors.

PMID- 24726759
TI  - Prescription opioid misuse among ED patients discharged with opioids.
AB  - STUDY OBJECTIVES: The purposes of this study were to determine the prevalence of
      prescription opioid misuse in a cohort of discharged emergency department (ED)
      patients who received prescription opioids and to examine factors predictive of
      misuse. METHODS: This prospective observational study enrolled a sample of ED
      patients aged 18 to 55 years who were discharged with a prescription opioid.
      Participants completed surveys at baseline in the ED, then 3 and 30 days later.
      Follow-up surveys contained questions about opioid use and misuse, including
      screening questions from the National Epidemiologic Survey on Alcohol and Related
      Conditions. Patients were categorized as misusers if they (1) self-escalated
      their dose, (2) obtained additional prescription opioids without a prescription,
      or (3) used for a reason besides pain. RESULTS: Of the 85 patients who completed
      follow-ups, 36 (42%) reported misuse at either 3 or 30 days. There was no
      difference in demographic variables, pain scores, analgesic treatment, or
      discharge diagnoses between misusers and nonmisusers. Self-escalation of dose was
      the most common category of misuse (33/36; 92%). Taking prescription opioids
      without a doctor's prescription was reported by 39% (14/36), and taking pain
      medications for a reason other than pain was reported by 36% (13/36). The
      presence of disability, chronic pain, preexisting prescription opioid use,
      oxycodone use, and past 12-month risk of substance abuse were associated with
      misuse. CONCLUSIONS: Prescription opioid misuse was prevalent among this cohort
      of ED patients. A heterogeneous mixture of behaviors was captured. Future
      research should focus on the etiologies of misuse with directed screening and
      interventions to decrease misuse.

PMID- 24726760
TI  - Documented electronic medical record-based pain intensity scores at a tertiary
      pediatric medical center: a cohort analysis.
AB  - CONTEXT: Previous surveys have suggested that pain in hospitalized patients
      remains undertreated. However, little is known about those with persistently high
      pain scores. OBJECTIVES: To document the distribution of scores and analyze the
      clinical characteristics of outliers with persistently high pain scores. METHODS:
      With institutional review board approval, a retrospective cohort analysis of more
      than 1.5 million documented scores was completed in a tertiary pediatric medical
      center during a three-year period. Patients with persistently high pain scores
      were identified for subgroup analysis. RESULTS: The median score was 0 (all
      years), and the means were 1.46, 1.34, and 1.3 in 2010, 2011, and 2012,
      respectively. Approximately 68% of admissions had at least one score of 4 or
      greater, although this level did not persist. Only 9% had mean scores of 4 or
      greater, and 1% (n = 492) had mean scores of 7 or greater. Scores remained high
      in patients within identifiable groups, that is, those with chronic pain (n =
      311), sickle cell vaso-occlusive episodes (n = 52), and pain in children with
      developmental and neuromuscular disorders (n = 32). Few had persistently high
      scores with acute pain but without known comorbidities (n = 56). CONCLUSION:
      Detailed review of clinical characteristics of patients with persistently high
      scores led to the strong impression that, in most cases, persistently high pain
      was not simply because of inadequate administration of opioids. Instead, the
      first step in improving pain management of hospitalized children may be the
      identification of outliers with high pain scores to direct efforts on the
      development of interventions for patient groups with mechanistically similar
      pain.

PMID- 24726761
TI  - Identifying the barriers and enablers to palliative care nurses' recognition and
      assessment of delirium symptoms: a qualitative study.
AB  - CONTEXT: Delirium is underrecognized by nurses, including those working in
      palliative care settings where the syndrome occurs frequently. Identifying
      contextual factors that support and/or hinder palliative care nurses' delirium
      recognition and assessment capabilities is crucial, to inform development of
      clinical practice and systems aimed at improving patients' delirium outcomes.
      OBJECTIVES: The aim of the study was to identify nurses' perceptions of the
      barriers and enablers to recognizing and assessing delirium symptoms in
      palliative care inpatient settings. METHODS: A series of semistructured
      interviews, guided by critical incident technique, were conducted with nurses
      working in Australian palliative care inpatient settings. A hypoactive delirium
      vignette prompted participants' recall of delirium and identification of the
      perceived factors (barriers and enablers) that impacted on their delirium
      recognition and assessment capabilities. Thematic content analysis was used to
      analyze the qualitative data. RESULTS: Thirty participants from nine palliative
      care services provided insights into the barriers and enablers of delirium
      recognition and assessment in the inpatient setting that were categorized as
      patient and family, health professional, and system level factors. Analysis
      revealed five themes, each reflecting both identified barriers and current and/or
      potential enablers: 1) value in listening to patients and engaging families, 2)
      assessment is integrated with care delivery, 3) respecting and integrating
      nurses' observations, 4) addressing nurses' delirium knowledge needs, and 5)
      integrating delirium recognition and assessment processes. CONCLUSION: Supporting
      the development of palliative care nursing delirium recognition and assessment
      practice requires attending to a range of barriers and enablers at the patient
      and family, health professional, and system levels.

PMID- 24726763
TI  - Priapism associated with iloperidone: a case report.
AB  - Priapism is a known side effect of antipsychotics. The causal mechanism seems to
      be mediated through alpha1-adrenergic receptor blockade which many antipsychotics
      are known to possess. We present the first detailed case of iloperidone-induced
      priapism in a patient with bipolar disorder with psychotic features. His case
      highlights some of the important risk factors clinicians should consider when
      using iloperidone, as it may be the highest-risk antipsychotic for causing
      priapism given it is a very potent blocker of the alpha-adrenergic receptor. 

PMID- 24726764
TI  - Hospital admission and community treatment of mental disorders in England from
      1998 to 2012.
AB  - OBJECTIVE: The number of psychiatric hospital beds in England has declined since
      the 1950s. Since the early 2000s, mental health staff increasingly work in
      community treatment teams. We analysed recent trends in hospital and community
      treatment in England for eight mental health diagnoses. METHOD: We obtained data
      from the UK Government Health and Social Care Information Centre covering the
      period 1998 to 2012. We analysed hospital admissions and length of stay for each
      diagnosis each year using linear regression. We studied associations among
      admissions, community treatment and hospital bed availability each year using
      structural equation modeling. RESULTS: The number of mental health beds fell 39%,
      from 37,000 in 1998 to 22,300 in 2012. Hospital admissions for five diagnoses
      declined significantly (depression, bipolar disorder, schizophrenia, dementia and
      obsessive compulsive disorder, P<.01 or P<.001). The strongest decline for
      depression involved 1000 fewer admissions each year. Admissions for three
      disorders increased significantly (posttraumatic stress disorder, eating
      disorders and alcohol-related disorders, P<.01 or P<.001). Alcohol-related
      admissions increased most strongly, by more than 1700 a year, and were
      significantly associated with increasing liver fibrosis and cirrhosis admissions
      (Pearson's r=0.89, P<.001) across the National Health Service (NHS) and the
      affordability of alcohol (Pearson's r=0.76, P<.01). The median length of stay
      declined significantly for four diagnoses (P<.001); the other four diagnoses did
      not change significantly. Depression had the steepest decline of almost 1 less
      day in hospital per admission per year. Almost 300 more patients were sectioned
      under the Mental Health Act each year. Community activity had relatively little
      effect on admissions, and its direct effect was not significantly different from
      zero. Years with more psychiatric beds had more admissions. CONCLUSIONS: Mental
      health bed numbers have declined significantly in England. Annual admissions and
      lengths of stay declined for a range of severe mental disorders including
      schizophrenia, bipolar disorder and depression. The fall in available beds can
      account for much of the decline in admissions. National reports of crisis team
      activity are not associated with declines in hospital admissions. There may be
      significant needs, especially of depressive patients, not being met by secondary
      community services, such as 24-hour observation and care. This calls for policy
      review and further epidemiological study of morbidity, mortality and health needs
      associated with mental disorder in the community.

PMID- 24726762
TI  - An analytical framework for delirium research in palliative care settings:
      integrated epidemiologic, clinician-researcher, and knowledge user perspectives.
AB  - CONTEXT: Delirium often presents difficult management challenges in the context
      of goals of care in palliative care settings. OBJECTIVES: The aim was to
      formulate an analytical framework for further research on delirium in palliative
      care settings, prioritize the associated research questions, discuss the inherent
      methodological challenges associated with relevant studies, and outline the next
      steps in a program of delirium research. METHODS: We combined multidisciplinary
      input from delirium researchers and knowledge users at an international delirium
      study planning meeting, relevant literature searches, focused input of
      epidemiologic expertise, and a meeting participant and coauthor survey to
      formulate a conceptual research framework and prioritize research questions.
      RESULTS: Our proposed framework incorporates three main groups of research
      questions: the first was predominantly epidemiologic, such as delirium occurrence
      rates, risk factor evaluation, screening, and diagnosis; the second covers
      pragmatic management questions; and the third relates to the development of
      predictive models for delirium outcomes. Based on aggregated survey responses to
      each research question or domain, the combined modal ratings of "very" or
      "extremely" important confirmed their priority. CONCLUSION: Using an analytical
      framework to represent the full clinical care pathway of delirium in palliative
      care settings, we identified multiple knowledge gaps in relation to the
      occurrence rates, assessment, management, and outcome prediction of delirium in
      this population. The knowledge synthesis generated from adequately powered,
      multicenter studies to answer the framework's research questions will inform
      decision making and policy development regarding delirium detection and
      management and thus help to achieve better outcomes for patients in palliative
      care settings.

PMID- 24726765
TI  - High-mobility group box 1 exacerbates CCl4-induced acute liver injury in mice.
AB  - High-mobility group box 1 (HMGB1) is a nuclear factor that can also serve as an
      imflammatory mediator once released into extracellular milieu. Therefore, HMGB1
      has been recognized to play a pivotal role in inflammatory diseases such as
      sepsis, acute lung injury, ischemia reperfusion injury and type 1 diabetes.
      Nevertheless, its impact on carbon tetrachloride (CCl4)-induced hepatic injury is
      yet to be elucidated. In the present report, we demonstrated evidence indicating
      that high levels of HMGB1 were not only present in the necrotic area of liver but
      also in the serum after CCl4 challenge. In line with these observations,
      administration of exogenous recombinant HMGB1 exacerbated CCl4-induced hepatic
      injury, while HMGB1 blocking antibody provided protection for mice against CCl4
      induced acute liver injury as evidenced by the decrease of serum transaminase and
      reduction of hepatic tissues necrosis. Mechanistic studies revealed that blockade
      of HMGB1 attenuated CCl4-induced MDA accumulation along with improved SOD and GSH
      activity. Treatment of mice with HMGB1 neutralizing antibody also significantly
      inhibited the production of proinflammatory mediators TNF-alpha and IL-6 along
      with attenuated HMGB1 expression and its extracellular release. Together, our
      data suggest an essential role for HMGB1 in CCl4-induced acute liver injury,
      while HMGB1 neutralizing antibody could be served as an effective regimen for
      preventing CCl4-induced acute liver injury.

PMID- 24726767
TI  - Effects of long-term exposure of 3,4-methylenedioxymethamphetamine (MDMA;
      "ecstasy") on neuronal transmitter transport, brain immuno-regulatory systems and
      progression of experimental periodontitis in rats.
AB  - The present study was designed to investigate the effects of long-term exposure
      (4 weeks) to the widely used narcotic drug and putative neurotoxicant 3,4
      methylenedioxymetamphetamine (MDMA; "ecstasy") on neuronal transmitter transport
      and progression of experimental periodontitis in male Wistar rats. The rats were
      exposed to MDMA (10mg/kg/day i.p.) or saline five days a week for four
      consecutive weeks. Exposure to MDMA induced a significant reduction in the
      synaptosomal reuptake of serotonin, while the uptake of dopamine was
      significantly increased 24h after the last injection of MDMA. In contrast, the
      synaptosomal uptake of noradrenaline and the vesicular uptake through the
      vesicular monoamine transporter 2 were not affected. In the experiments of
      periodontitis development, ligature-induced periodontitis was induced three days
      prior to MDMA administration. Compared to controls, MDMA-treated rats developed
      significantly more periodontitis. In conclusion, our results show that long-term
      exposure to MDMA affects the serotonergic and dopaminergic transport systems in
      the rat brain and increased the susceptibility to the psychosomatic ailment
      periodontitis following disturbances of brain immune-regulatory systems. These
      results are interesting with respect to recent research showing that changes in
      neurotransmitter signalling may alter the reactivity of brain-controlled
      immunoregulatory systems controlling pathogenic microorganisms colonizing mucosal
      surfaces.

PMID- 24726766
TI  - Identification of target antigens of anti-endothelial cell antibodies in patients
      with anti-neutrophil cytoplasmic antibody-associated vasculitides: a proteomic
      approach.
AB  - Anti-endothelial cell antibodies (AECAs) have been reported to cause endothelial
      cell dysfunction, but their specific targets have never been identified in anti
      neutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAVs). Proteins
      from human umbilical vein endothelial cells (HUVECs) were separated by 2
      dimensional electrophoresis (2-DE). 2-D immunoblots were used to compare serum
      IgG reactivities from 30 patients with AAV and 12 healthy controls (HCs).
      Proteins identified as target antigens by MALDI- TOF-TOF mass spectrometry
      included lamin A/C, vimentin, alpha-enolase, far upstream binding protein 2
      (FUBP2) and protein disulfide-isomerase A3 precursor (PDIA3). Antibodies
      targeting lamin A, vimentin, alpha-enolase, FUBP2 and PDIA3 were identified in
      57.1%, 64.3%, 35.7%, 50% and 0% of patients with microscopic polyangiitis and 8%,
      3.3%, 7.2%, 0% and 6.7% of HCs respectively. IgG from patients with microscopic
      polyangiitis had stronger reactivity against HUVEC than other groups and HCs and
      induced stronger Erk phosphorylation in HUVECs than IgG from HCs.

PMID- 24726768
TI  - Analysis of smoking and LPO in ALS.
AB  - Smoking has been suggested as one of the risk factor for amyotrophic lateral
      sclerosis (ALS) development. In order to investigate whether adverse effects of
      cigarette smoke in ALS have any association with increase in oxidative stress,
      disease severity, lipid hydroperoxides (LPO) and superoxide dismutase-1 (SOD1)
      levels were measured in biofluids of smoker and never smoker ALS patients and
      clinically correlated. Serum and CSF from sporadic ALS patients (n=50) diagnosed
      with El Escorial criteria were collected in the study. Serum (n=50) and CSF
      (n=42) were also collected from normal healthy controls. The LPO levels were
      estimated using commercially available kits. Enzyme-linked immunosorbent assays
      (ELISAs) were used to quantitate SOD1. Their levels were further analyzed among
      smoker and never smoker subjects. Significantly elevated LPO in sera and CSF of
      ALS patients were observed (p<0.05). There was considerably increased LPO in sera
      and CSF of smoker ALS subjects matched with disease severity as compared to never
      smoker ALS (p<0.05). ALS group did not show any alteration in SOD1 when compared
      to controls (p>0.05). In addition, no change has been observed in SOD1 levels in
      ALS subjects who smoke (p>0.05). Increased LPO and unaltered SOD1 in ALS patients
      may suggest the neuro-pathological association of LPO with ALS disease
      independent of SOD1. With current findings, it may be proposed that LPO levels
      might constitute as probable biomarker for smoker ALS patients, however, it
      cannot be concluded without larger gender matched studies. Additional
      investigations are needed to determine whether LPO upregulation is primary or
      secondary to motor neuron degeneration in ALS.

PMID- 24726769
TI  - GABA release provoked by disturbed Na(+), K(+) and Ca(2+) homeostasis in
      cerebellar nerve endings: roles of Ca(2+) channels, Na(+)/Ca(2+) exchangers and
      GAT1 transporter reversal.
AB  - GABA release provoked by ion dysregulations typical of some neuropathological
      conditions was analyzed in purified cerebellar synaptosomes pre-labeled with
      [(3)H]GABA and exposed in superfusion to KCl, 4-aminopyridine (4-AP) or
      veratridine. The overflows caused by relatively low concentrations of the
      releasers were almost totally external Ca(2+)-dependent. Higher concentrations of
      KCl or veratridine, but not 4-AP, involved also external Ca(2+)-independent
      mechanisms. The GABA overflows evoked by veratridine and, less so, the overflow
      evoked by high K(+), occurred in part by reversal of the GAT1 transporter. None
      of the depolarizing agents activated store-operated or transient receptor
      potential or L-type Ca(2+) channels. Only the overflow caused by 4-AP occurred in
      part by N- and P/Q-type voltage-sensitive calcium channel-dependent exocytosis.
      Significant portions of the external Ca(2+)-dependent overflows evoked by the
      three releasers involved reversal of plasmalemmal Na(+)/Ca(2+) exchangers. The
      overflows evoked by high K(+) or veratridine, but not by 4-AP were evoked by
      Ca(2+) originated through mitochondrial Na(+)/Ca(2+) exchangers. Ca(2+)-induced
      Ca(2+) release mediated by inositoltrisphosphate receptors participated
      exclusively in the GABA release stimulated by high KCl which also occurred in a
      modest portion through anion channels. Important differences could be observed
      between the release mechanisms of GABA here described and those previously
      reported for glycine, in spite of the abundant vesicular co-localization of the
      two transmitters in cerebellar interneurons. 

PMID- 24726770
TI  - Peripheral administration of an anti-TNF-alpha receptor fusion protein
      counteracts the amyloid induced elevation of hippocampal TNF-alpha levels and
      memory deficits in mice.
AB  - Alzheimer's disease has long been associated with increased inflammation in the
      brain. Activated microglia and increased production of the inflammatory cytokines
      such as TNF-alpha, have been proposed to contribute to the onset and progression
      of the disease. We investigated if systemic administration of an anti-tumor
      necrosis factor (TNF) biologic medication clinically validated for rheumatoid
      arthritis (RA), TNF receptor 2 fused to a Fc domain (TNFR2:Fc), could ameliorate
      the behavioral symptoms and decrease neuroinflammation in a non-transgenic mouse
      model mimicking some hallmarks of the disease. Seven days after a single
      intracebroventricular (icv) injection of aggregated amyloid beta25-35 (9nmoles),
      mice displayed significant cognitive deficit in spontaneous alternation (working
      memory) and inhibitory avoidance (long-term memory) tasks. Alternation percentage
      decreased from 72.4%+/-1.3 to chance level (52.6%+/-1.7); step-through retention
      latency decreased from 247s to 144s. Subcutaneous administration of 30mg/kg
      TNFR2:Fc every second day post amyloid beta25-35 icv administration counteracted
      the amyloid-induced decrease in alternation percentage (66.4s+/-1.8) and the
      decreased step-through retention latency (248s+/-9). Measurement of hippocampal
      TNF-alpha levels by ELISA after behavioral assessment showed significant
      elevation in animals injected with amyloid beta25-35 relative to animals injected
      with control peptide. In animals treated with 30mg/kg TNFR2:Fc, TNF-alpha levels
      in the hippocampus were reduced and were similar to control animals. These data
      suggest that peripheral administration of TNFR2:Fc counteracts amyloid-induced
      memory impairment and normalizes increased TNF-alpha levels in hippocampus of a
      non-transgenic mouse model of amyloid induced cognitive deficit. 

PMID- 24726771
TI  - Assessment of heavy metal impact on sediment quality of the Xiaoqinghe estuary in
      the coastal Laizhou Bay, Bohai Sea: inconsistency between two commonly used
      criteria.
AB  - Surface sediments in the Xiaoqinghe estuary, southwestern coastal Laizhou Bay,
      were examined to assess the bio-toxic risk of heavy metals (Cd, Cu, Ni, Pb and
      Zn) with the effects range-low and effects range-median guidelines (ERL-ERMs) and
      the concentration ratio of simultaneously extractable metals to acid volatile
      sulfides ([SEM]/[AVS]). Based on the ERL-ERM guidelines, bio-toxic effect caused
      by Cu, Ni, Pb and Zn could be expected in the riverine surface sediments of the
      Xiaoqinghe estuary; and the surface sediments in the marine area were in good
      quality and only Ni might cause bio-toxic effect occasionally. The AVS-SEM
      guidelines revealed that no bio-toxic effect could be caused by any of the
      studied metals in both the riverine and marine sediments, since there were excess
      sulfides in surface sediments which could form water-insoluble substances with
      free metal ions and reduce the bioavailability of heavy metals. 

PMID- 24726772
TI  - Seagrass importance for a small-scale fishery in the tropics: the need for
      seascape management.
AB  - Small-scale fisheries (SSF) in tropical seascapes (mosaics of interconnected
      mangroves, seagrasses and corals) are crucial for food and income. However,
      management is directed mostly to corals and mangroves. This research analyzes the
      importance of seagrasses compared to adjacent ecosystems in Chwaka Bay, Zanzibar,
      Tanzania. Using fish landings; the study investigated: location of fishing
      effort, fish production (biomass and species), and monetary benefits (aggregated
      value and per capita income). Seagrasses were the most visited grounds providing
      highest community benefits. Per capita benefits were equivalent to those from
      corals and mangroves. All three habitats provided income just above extreme
      poverty levels; however catches from seagrass appeared more stable. Seagrass are
      key ecosystems supporting SSF and protection and management are urgently needed.
      Adoption of a seascape approach considering all ecosystems underpinning SSF and
      the social aspects of fishing and a shift in emphasis from pure conservation to
      sustainable resource management would be desirable. 

PMID- 24726773
TI  - Simultaneous nitrification/denitrification and trace organic contaminant (TrOC)
      removal by an anoxic-aerobic membrane bioreactor (MBR).
AB  - Simultaneous nitrification/denitrification and trace organic contaminant (TrOC)
      removal during wastewater treatment by an integrated anoxic-aerobic MBR was
      examined. A set of 30 compounds was selected to represent TrOCs that occur
      ubiquitously in domestic wastewater. The system achieved over 95% total organic
      carbon (TOC) and over 80% total nitrogen (TN) removal. In addition, 21 of the 30
      TrOCs investigated here were removed by over 90%. Low oxidation reduction
      potential (i.e., anoxic/anaerobic) regimes were conducive to moderate to high
      (50% to 90%) removal of nine TrOCs. These included four pharmaceuticals and
      personal care products (primidone, metronidazole, triclosan, and amitriptyline),
      one steroid hormone (17beta-estradiol-17-acetate), one industrial chemical (4
      tert-octylphenol) and all three selected UV filters (benzophenone, oxybenzone,
      and octocrylene). Internal recirculation between the anoxic and aerobic
      bioreactors was essential for anoxic removal of remaining TrOCs. A major role of
      the aerobic MBR for TOC, TN, and TrOC removal was observed. 

PMID- 24726774
TI  - Influence of headspace composition on product diversity by sulphate reducing
      bacteria biocathode.
AB  - Mixed culture of sulphate reducing bacteria named TERI-MS-003 was used for
      development of biocathode on activated carbon fabric fastened to stainless steel
      mesh for conversion of volatile fatty acids to reduced organic compounds under
      chronoamperometric conditions of -0.85V vs. Ag/AgCl (3.5M KCl). A range of
      chemicals were bioelectrosynthesized, however the gases present in headspace
      environment of the bioelectrochemical reactor governed the product profile.
      Succinate, ethanol, hydrogen, glycerol and propionate were observed to be the
      predominant products when the reactor was hermetically sealed. On the other hand,
      acetone, propionate, isopropanol, propanol, isobutyrate, isovalerate and
      heptanoate were the predominant products when the reactor was continuously
      sparged with nitrogen. This study highlights the importance of head space
      composition in order to manoeuvre the final product profile desired during a
      microbial electro-synthesis operation and the need for simultaneously developing
      effective separation and recovery strategies from an economical and practical
      standpoint. 

PMID- 24726775
TI  - Preliminary studies on cryopreservation of snakehead (Channa striata) embryos.
AB  - This paper reports the findings of the ongoing studies on cryopreservation of the
      snakehead, Channa striata embryos. The specific objective of this study was to
      collect data on the sensitivity of C. striata embryo hatching rate to low
      temperatures at two different developmental stages in the presence of four
      different cryoprotectants. Embryos at morula and heartbeat stages were selected
      and incubated in 1M dimethyl sulfoxide (Me2SO), 1M ethylene glycol (EG), 1M
      methanol (MeOH) and 0.1M sucrose solutions at different temperatures for a period
      of time. Embryos were kept at 24  degrees C (control), 15  degrees C, 4  degrees
      C and -2  degrees C for 5 min, 1h and 3h. Following these treatments, the embryos
      were then transferred into a 24  degrees C water bath until hatch to evaluate the
      hatching rate. The results showed that there was a significant decrease of
      hatching rate in both developmental stages following exposure to 4  degrees C and
      -2  degrees C at 1h and 3h exposure in each treatment. Heartbeat stage was more
      tolerant against chilling at -2  degrees C for 3h exposure in Me2SO followed by
      MeOH, sucrose and EG. Further studies will be conducted to find the best method
      to preserve embryos for long term storage.

PMID- 24726776
TI  - Explaining trends in addictive behaviour policy--the role of policy coherence.
AB  - This article analyses addictive behaviour policy regimes - focusing on illegal
      drugs and gambling - in 19 countries over a period of 50 years. It compares how
      these countries have combined rules on the consumption and possession of cannabis
      and on the participation in sports betting with sanctions for violations of these
      rules. While theories of policy convergence can explain dominant trends in the
      way the combination of these policy instruments have changed, they cannot account
      for all of the empirical variation observed. Turning to Portugal, a case which
      deviates in both illegal drug and gambling policy from the expected trend, we
      show that explanations of policy change improve substantially when taking the
      concept of policy coherence into account. Specifically, we argue that changes of
      the policy status quo are facilitated when policy entrepreneurs succeed in
      shaping a perception of policy incoherence. In turn, when relevant actors are
      able to maintain a perception of policy coherence, the policy status quo is
      stabilized. 

PMID- 24726777
TI  - Locking plates and their effects on healing conditions and stress distribution: A
      femoral neck fracture study in cadavers.
AB  - BACKGROUND: Implants are used to stabilize femoral neck fractures to achieve
      successful fracture healing, but there is still a high rate of fracture non
      unions. We compared micromotions in femurs with fractured femoral necks
      stabilized with three screws with or without a locking plate. We also
      investigated whether osteoporosis was associated with micromotion magnitudes, and
      explored the influence of implants on load distribution in the upper femur.
      METHODS: Twelve pairs of human cadaver femurs with femoral neck fractures (AO/OTA
      31-B1) were allocated to fracture fixation by three locked screws or three
      individual screws. All femurs underwent dual energy X-ray absorptiometry.
      Physiological subject-specific axial load and torque was applied for
      10,000cycles. Micromotion of the head fragment was measured every 100cycles with
      high-resolution optical motion detection. Load distribution was measured with
      strain-gauge rosettes attached to the lateral and medial proximal diaphysis.
      FINDINGS: The locking plate group showed reduced micromotion about the femoral
      neck axis (P=0.035, effect size=0.62). No differences were found in valgus-varus
      or antegrade-retrograde rotations, or in the three translations. Micromotion
      magnitudes were not associated with osteoporosis. The overall micromotions of the
      upper femur and the load distribution in the proximal diaphysis were not
      influenced by fixation type. INTERPRETATION: The locking plate group showed
      increased resistance to shear forces compared with the screw group. This effect
      was not associated with a diagnosis of osteoporosis. The locking plate did not
      affect the load distribution in the proximal femur.

PMID- 24726778
TI  - In vitro biomechanical evaluation of fibular movement in below knee amputations.
AB  - BACKGROUND: In below knee amputations, the remaining fibula may be subjected to
      abnormal forces resulting in problematic tibia-fibular movement. The purpose of
      the current work was to examine the effect of amputation length and interosseous
      membrane integrity on fibular movement when subjected to unopposed biceps femoris
      muscle tension. METHODS: Forty embalmed cadaveric specimens were subjected to a
      below knee amputation with fibular lengths of 5cm and 10cm. A subset of specimens
      (n=20) was further modified by sectioning the interosseous membrane. The tibias
      were mounted in a material testing machine and the biceps femoris was sutured to
      the actuator. Position-controlled tensile cyclic loading was applied (initial
      displacement of 4mm for 100 cycles at 0.5Hz with increments of 2mm up to 20mm) to
      the biceps femoris. The kinematics of the fibula with respect to the tibia was
      analyzed for three degrees of freedom: abduction, flexion and rotation. FINDINGS:
      There was no interaction between below knee amputation length and interosseous
      membrane integrity on the degree of abduction, flexion, and rotation. However,
      below knee amputations with a sectioned interosseous membrane are abducted to a
      significantly greater degree than intact interosseous membrane below knee
      amputations. Furthermore, although embalmed specimens were tested here, embalming
      was consistent across specimens and it is unlikely that this confounded the
      findings. INTERPRETATION: Understanding the cause of fibular abduction in below
      knee amputation will lead to recommendations for preventive surgical and
      rehabilitative measures.

PMID- 24726779
TI  - On the use of continuous relative phase: Review of current approaches and outline
      for a new standard.
AB  - BACKGROUND: In this paper we review applications of continuous relative phase and
      commonly reported methods for calculating the phase angle. Signals with known
      properties as well as empirical data were used to compare methods for calculating
      the phase angle. FINDINGS: Our results suggest that the most valid, robust and
      intuitive results are obtained from the following steps: 1) centering the
      amplitude of the original signals around zero, 2) creating analytic signals from
      the original signals using the Hilbert transform, 3) calculating the phase angle
      using the analytic signal and 4) calculating the continuous relative phase.
      INTERPRETATIONS: The resulting continuous relative phase values are free of
      frequency artifacts, a problem associated with most normalization techniques, and
      the interpretation remains intuitive. We propose these methods for future
      research using continuous relative phase in studies and analyses of human
      movement coordination.

PMID- 24726780
TI  - Hip abductor function in individuals with medial knee osteoarthritis:
      Implications for medial compartment loading during gait.
AB  - BACKGROUND: Hip abductor muscles generate moments of force that control lower
      extremity frontal plane motion. Strengthening these muscles has been a recent
      trend in therapeutic intervention studies for knee osteoarthritis. The current
      study investigated the relationship between hip abductor muscle function
      (strength and activation) and the net external knee adduction moment during gait
      in those with medial compartment knee osteoarthritis. METHODS: 54 individuals
      with moderate knee osteoarthritis walked at their self-selected velocity while
      gluteus medius electromyograms, segment motions and ground reaction forces were
      recorded. Net external knee adduction moment (KAM) and linear enveloped
      electromyographic profiles were calculated. Peak KAM was determined and then
      principal component analyses (PCA) were applied to KAM and electromyographic
      profiles. Isometric hip abductor strength, anthropometrics and gait velocity were
      measured. Multiple regression models evaluated the relationship between walking
      velocity, hip abductor strength, electromyographic variables recorded during gait
      and KAM waveform characteristics. FINDINGS: Minimal peak KAM variance was
      explained by abductor strength (R(2)=9%, P=0.027). PCA-based KAM waveform
      characteristics were not explained by abductor strength. Overall gluteus medius
      amplitude (PP1-scores) was related to a reduction in the bi-modal KAM (PP3
      scores) pattern (R(2)=16%, P=0.003). INTERPRETATION: There was no clear
      relationship between hip abductor muscle strength and specific amplitude and
      temporal KAM characteristics. Higher overall gluteus medius activation amplitude
      was related to a sustained KAM during mid-stance. 84 to 90% of the variance in
      KAM waveform characteristics was not explained by hip abductor muscle function
      showing hip abductor muscle function has minimal association to KAM
      characteristics.

PMID- 24726781
TI  - Role of genotype-based approach in the clinical management of adult acute myeloid
      leukemia with normal cytogenetics.
AB  - Acute myeloid leukemia (AML) is the most common form of acute leukemia affecting
      adults. Although it is a complex disease driven by numerous genetic and
      epigenetic abnormalities, nearly 50% of patients exhibit a normal karyotype (CN
      AML) with an intermediate cytogenetic risk. However, a widespread genomic
      analysis has recently shown the recurrence of genomic aberrations in this
      category (mutations of FLT3, CEBPA, NPM1, RUNX1, TET2, IDH1/2, DNMT3A, ASXL1, MLL
      and WT1) thus revealing its marked genomic heterogeneity. In this perspective, a
      global gene expression analysis of AML patients provides an independent
      prognostic marker to categorize each patient into clinic-pathologic subgroups
      based on its molecular genetic defects. Consistently such classification, taking
      into account the uniqueness of each AML patient, furnishes an individualized
      treatment approach leading a step closer to personalized medicine. Overall the
      genome-wide analysis of AML patients, by providing novel insights into biology of
      this tumor, furnishes accurate prognostic markers as well as useful tools for
      selecting the most appropriate treatment option. Moreover it provides novel
      therapeutic targets useful to enhance efficacy of the current anti-AML
      therapeutics. Here we describe the prognostic relevance of such new genetic data
      and discuss how this approach can be used to improve survival and treatment of
      AML patients. 

PMID- 24726782
TI  - VEGF in chronic myeloid leukemia treated with interferon and imatinib.

PMID- 24726783
TI  - Survey of pediatric urologists on the preoperative use of testosterone in the
      surgical correction of hypospadias.
AB  - OBJECTIVE: To better characterize the current state of testosterone use in the
      surgical correction of hypospadias among pediatric urologists. METHODS: An email
      was sent via the pedsurology research listserv through the American Academy of
      Pediatrics, inviting members to participate in an anonymous survey regarding
      their use of preoperative testosterone in hypospadias correction. RESULTS: Twenty
      seven responses were obtained for a response rate of 53%. Almost all responders
      practiced in North America, had exclusively pediatric patients in their practice,
      and had been in practice for 30 years or less. 55% were classified as high-volume
      surgeons, completing >50 cases yearly, 87% of whom use preoperative androgen
      therapy currently, compared with 67% of low-volume surgeons. Testosterone was
      prescribed primarily for a small appearing penis, reduced glans circumference,
      reduced urethral plate width, and/or proximal hypospadias. The effect of
      testosterone was determined primarily by evaluating penile appearance (59%).
      However, the majority (56%) of physicians stopped giving testosterone when they
      completed a predetermined regimen. CONCLUSIONS: While many pediatric urologists
      use testosterone prior to hypospadias repair, the practice patterns are variable.
      It appears that the use of testosterone is primarily limited to patients with
      proximal hypospadias, small appearing penis, reduced glans circumference or
      reduced urethral plate.

PMID- 24726784
TI  - Motivations, aims and communication around advance directives: a mixed-methods
      study into the perspective of their owners and the influence of a current
      illness.
AB  - OBJECTIVE: What are motivations of owners of an advance directive (AD) to draft
      an AD, what do they aim for with their AD and do they communicate about their AD?
      METHODS: Written questionnaires were sent to a cohort of people owning different
      types of ADs (n=5768). A purposive sample of people suffering from an illness was
      selected from the cohort for an in-depth interview (n=29). RESULTS: About half of
      our population had no direct motivation to draft their AD. Most mentioned
      motivation for the other half was an illness of a family member or friend. Many
      different and specific aims for drafting an AD were mentioned. An often mentioned
      more general aim in people with different ADs was to prevent unnecessary
      lengthening of life or treatment (14-16%). Most respondents communicated about
      having an AD with close-ones (63-88%) and with their GP (65-79%). In the
      interviews people gave vivid examples of experiences of what they hoped to
      prevent at the end of life. Some mentioned difficulties foreseeing the future and
      gave examples of response shift. CONCLUSION: ADs can give directions to
      caregivers about what people want at the end of life. PRACTICE IMPLICATIONS: ADs
      have to be discussed in detail by their owners and caregivers, since owners often
      have specific aims with their AD.

PMID- 24726785
TI  - The effects of a transtheoretical model-based exercise stage-matched intervention
      on exercise behavior in patients with coronary heart disease: a randomized
      controlled trial.
AB  - OBJECTIVE: To determine whether a transtheoretical model-based exercise stage
      matched intervention (ESMI) has positive effects on the exercise behavior of
      sedentary patients with coronary heart disease (CHD). METHODS: The study was a
      randomized controlled trial with a repeated measures design. Participants (N=196)
      were randomly allocated to either a conventional (C) group, a patient education
      (PE) group, or an ESMI group. Exercise behavior was measured by exercise stages
      of change, exercise self-efficacy, exercise decisional balance, and duration of
      moderate exercise at baseline, immediate post-intervention, and at 3- and 6-month
      follow-up. RESULTS: Our results showed that the ESMI group demonstrated a more
      positive shift in exercise stages of change (p<0.01), higher exercise self
      efficacy (p<0.01), greater exercise benefits (p<0.01), fewer exercise barriers
      (p<0.01), and longer moderate exercise duration (minutes/week) (p<0.01) after
      completion of the 8-week intervention compared with the C and PE groups. These
      significantly positive effects were maintained at 3- and 6-month follow-up.
      CONCLUSION: The transtheoretical model-based ESMI had significantly positive
      effects on the exercise behavior of sedentary CHD patients. PRACTICE
      IMPLICATIONS: It is important to provide a structured education program for CHD
      patients, preferably guided by the transtheoretical model.

PMID- 24726786
TI  - Contamination risk for operators performing semi-closed HIPEC procedure using
      cisplatin.
AB  - AIMS: Aim of this study was to assess operators' safety while performing a semi
      closed HIPEC procedure for peritoneal carcinomatosis using cisplatin drugs.
      METHODS: Environmental air, theater personnel urine, operators' gloves and hand
      skin contamination were assessed during two non-consecutive working days. Six
      operating surgeons, two anesthesiologists and two theater nurses were included in
      the study. Glove samples were collected from the inner surface of the external
      glove and from the external surface of the inner glove from operating surgeons
      wearing a double pair of gloves. Personnel urine samples were collected before,
      after and 24 h from the procedure. RESULTS: Air and urine samples permanently
      resulted below detectable levels for cisplatin presence on all the tested sources
      and sessions. Cisplatin contamination was detected on the inner surface of the
      external gloves and on the outer surface of the inner gloves, but in a lower
      concentration for the latter. Skin wipe samples were below detectable levels for
      platinum presence. CONCLUSION: The results suggest that two pairs of gloves are
      adequate to protect the skin from antiblastic drugs. No sign of direct contact or
      systemic absorption of drugs was ever detected from the inspected samples. Semi
      closed HIPEC technique appears to be a safe procedure for operators.

PMID- 24726787
TI  - Acquisition and biosynthesis of saturated and unsaturated fatty acids by
      trypanosomatids.
AB  - As components of phospholipids and glycosylphosphatidylinositol anchors, fatty
      acids are responsible for forming the core of biological membranes and the
      correct localization of proteins within membranes. They also contribute to
      anchoring proteins by direct acylation of specific amino acids. Fatty acids can
      be used as energy sources and serve as signaling molecules or precursors for
      their synthesis. All these processes highlight the important role of fatty acids
      in cell physiology, justifying the diverse strategies for their acquisition
      evolved by different organisms. This review describes several recent findings in
      the salvage and biosynthesis of fatty acids by parasitic protists belonging to
      the class Kinetoplastea. They include two biosynthetic routes, the mitochondrial
      one and a peculiar membrane-associated pathway, the synthesis of polyunsaturated
      fatty acids, and the scavenging of lysophospholipids and lipoproteins from host
      plasma. These different processes are also explored as putative targets for
      chemotherapy. 

PMID- 24726788
TI  - Progesterone protects normative anxiety-like responding among ovariectomized
      female mice that conditionally express the HIV-1 regulatory protein, Tat, in the
      CNS.
AB  - Increased anxiety is co-morbid with human immunodeficiency virus (HIV) infection.
      Actions of the neurotoxic HIV-1 regulatory protein, Tat, may contribute to
      affective dysfunction. We hypothesized that Tat expression would increase anxiety
      like behavior of female GT-tg bigenic mice that express HIV-1 Tat protein in the
      brain in a doxycycline-dependent manner. Furthermore, given reports that HIV
      induced anxiety may occur at lower rates among women, and that the neurotoxic
      effects of Tat are ameliorated by sex steroids in vitro, we hypothesized that
      17beta-estradiol and/or progesterone would ameliorate Tat-induced anxiety-like
      effects. Among naturally-cycling proestrous and diestrous mice, Tat-induction via
      7days of doxycycline treatment significantly increased anxiety-like responding in
      an open field, elevated plus maze and a marble-burying task, compared to
      treatment with saline. Proestrous mice demonstrated less anxiety-like behavior
      than diestrous mice in the open field and elevated plus maze, but these effects
      did not significantly interact with Tat-induction. Among ovariectomized mice,
      doxycycline-induced Tat protein significantly increased anxiety-like behavior in
      an elevated plus maze and a marble burying task compared to saline-treated mice,
      but not an open field (where anxiety-like responding was already maximal). Co
      administration of progesterone (4mg/kg), but not 17beta-estradiol (0.09mg/kg),
      with doxycycline significantly ameliorated anxiety-like responding in the
      elevated plus maze and marble burying tasks. When administered together, 17beta
      estradiol partially antagonized the protective effects of progesterone on Tat
      induced anxiety-like behavior. These findings support evidence of steroid
      protection over HIV-1 proteins, and extend them by demonstrating the protective
      capacity of progesterone on Tat-induced anxiety-like behavior of ovariectomized
      female mice. 

PMID- 24726790
TI  - Patient education after amputation: systematic review and experts' opinions.
AB  - OBJECTIVE: To perform a systematic review of the literature regarding amputee
      self-care, and analyze current experts' opinions. METHOD: The research in Medline
      and Cochrane Library databases was performed using the keywords "amputee self
      care", "amputee health care", "amputee education", and "amputee health
      management". The methodological quality of the articles was assessed using four
      levels of evidence and three guideline grades (A: strong; B: moderate; C: poor).
      RESULT: One prospective randomized controlled study confirm the level of evidence
      of self-care amputee persons with grade B, which is similar others chronic
      diseases self-care. Self-care of amputee persons contributes to improve
      functional status, depressive syndrome, and also health-related quality of life.
      A review of the patients' needs and expectations in self-care amputee persons has
      been established thanks to the presence of qualitative focus group study.
      CONCLUSION: A multidisciplinary self-care of amputee persons can be recommended.
      Regarding literature date, the level of evidence of self-care amputee persons is
      moderate (grade B). Experts groups are currently working on a self-care amputee
      persons guideline book in order to standardize practicing and programs in the
      physical medicine and rehabilitation departments.

PMID- 24726789
TI  - Beyond physiological hypoarousal: the role of life stress and callous-unemotional
      traits in incarcerated adolescent males.
AB  - The development of antisocial behavior in youth has been examined with
      neurobiological theories that suggest that adolescents who are less responsive to
      their environments are less likely to develop empathy in the absence of extant
      physiological arousal. However, little attention is paid to these individuals'
      social context. Individuals with adverse early experiences can also exhibit
      attenuated physiological arousal. The current investigation examines whether
      psychopathic symptoms or life stress exposure is associated with cortisol and its
      diurnal rhythm within 50 incarcerated adolescent boys (14-18years old). Ten
      saliva cortisol samples were collected 1-2weeks after admission to a maximum
      security juvenile facility. Hierarchical Linear Modeling distinguished waking
      cortisol levels, the awakening response (CAR) and the diurnal rhythm. Multiple
      interviews and self-report measures of CU traits and stressor exposure were
      collected. Boys with higher levels of CU traits or greater life stress exposure
      had flat diurnal rhythms and a steeper awakening response in analyses with
      lifetime stress exposure specifically. Nonetheless, boys who were elevated on
      both CU traits and prior stress exposure had steeper diurnal rhythms. These
      results extend neurobiological theories of cortisol and illustrate that boys with
      the combination of severe stress with CU traits have a unique physiological
      profile. 

PMID- 24726791
TI  - Acrylamide alters neurotransmitter induced calcium responses in murine ESC
      derived and primary neurons.
AB  - Stem cell-derived specialized cell types are of interest as an alternative cell
      system to identify and research neurotoxic effects and modes of action.
      Developmental toxicity may be studied during differentiation, while organ
      specific toxicity may be assessed in fully functional cells, such as neurons. In
      this study we tested if fully differentiated neurons derived from murine
      embryonic stem cells (ESCN) could be used to investigate the effects of the well
      characterized neurotoxic model compound acrylamide (ACR) and if ESCN behave
      similar to murine primary cortical neurons (pCN) from 16 days old embryos. We
      characterized the differentiation process of cryopreserved ESC-derived neural
      precursor cells (NPC) differentiating to ESCN. During the differentiation process
      (days 11-20) a strong increase in calcium responses to glutamate, acetylcholine
      and GABA were observed. Moreover, neuron specific marker proteins, beta-III
      tubulin, MAP2, Tau, Rbfox3 and synaptophysin showed similar patterns to pCN. In
      ESCN and pCN the neuronal structure, e.g. neurites, was not affected by low
      concentrations of ACR [0.5-1.6mM]. However, 24h incubation periods with 0.5-1.6mM
      ACR led to a reduction of acetylcholine and glutamate induced calcium responses.
      In conclusion, we show that non-cytotoxic concentrations of ACR alter
      neurotransmission in ESCN as well as pCN. 

PMID- 24726792
TI  - Airborne manganese as dust vs. fume determining blood levels in workers at a
      manganese alloy production plant.
AB  - The appropriate exposure metrics for characterizing manganese (Mn) exposure
      associated with neurobehavioral effects have not been established. Blood levels
      of Mn (B-Mn) provide a potentially important intermediate marker of Mn airborne
      exposures. Using data from a study of a population of silicon- and ferro
      manganese alloy production workers employed between 1973 and 1991, B-Mn levels
      were modeled in relation to prior Mn exposure using detailed work histories and
      estimated respirable Mn concentrations from air-sampling records. Despite wide
      variation in exposure levels estimated for individual jobs, duration of
      employment (exposure) was itself a strong predictor of B-Mn levels and strongest
      when an 80-day half-life was applied to contributions over time (t=6.95, 7.44,
      respectively; p<10(-5)). Partitioning exposure concentrations based on process
      origin into two categories: (1) "large" respirable particulate (Mn-LRP) derived
      mainly from mechanically generated dust, and (2) "small" respirable particulate
      (Mn-SRP) primarily electric furnace condensation fume, revealed that B-Mn levels
      largely track the small, fume exposures. With a half-life of 65 days applied in a
      model with cumulative exposure terms for both Mn-LRP (t=-0.16, p=0.87) and Mn-SRP
      (t=6.45, p<10(-5)), the contribution of the large-size fraction contribution was
      negligible. Constructing metrics based on the square root of SRP exposure
      concentrations produced a better model fit (t=7.87 vs. 7.44, R(2)=0.2333 vs.
      0.2157). In a model containing both duration (t=0.79, p=0.43) and (square root)
      fume (t=2.47, p=0.01) metrics, the duration term was a weak contributor. Furnace
      derived, small respirable Mn particulate appears to be the primary contributor to
      B-Mn levels, with a dose-rate dependence in a population chronically exposed to
      Mn, with air-concentrations declining in recent years. These observations may
      reflect the presence of homeostatic control of Mn levels in the blood and other
      body tissues and be useful in assessing Mn exposures for evaluating neurotoxic
      effects. 

PMID- 24726793
TI  - Expression of Toll-Like Receptors in peripheral blood mononuclear cells and
      response to cognitive-behavioral therapy in major depressive disorder.
AB  - In recent years, increased attention has been paid to the inflammatory mechanisms
      of major depressive disorder (MDD). The aim of the present study was to
      investigate pro-inflammatory pathways related to the "leaky gut" hypothesis of
      MDD, which is based on the putative intestinal translocation of Gram-negative
      bacteria and a subsequent abnormal immune response mediated by the Toll-Like
      Receptor-4 (TLR-4) pathway. 50 patients with first-episode MDD and 30 healthy
      control subjects participated in the study. Real-time quantitative PCR was used
      to measure TLR-4 and TLR-2 RNA from peripheral mononuclear blood cells, as well
      as the expression of NF-kappabeta, a key transcription factor of the pro
      inflammatory response. TLR-4 protein expression was determined by using flow
      cytometry. TLR-2 served as a control molecule. Low-grade inflammation was
      characterized by the measurement of interleukin-6 (IL-6) and C-reactive protein
      (CRP). Bacterial translocation was investigated by the measurement of the 16S
      rRNA subunit (16S rDNA) of intestinal microbiota in the blood plasma of the
      participants. We performed these analyses before (t1) and after (t2) cognitive
      behavioral therapy (CBT) in MDD. The healthy control subjects were also assessed
      two times. We found significantly elevated expressions of all three markers (TLR
      4 RNA and protein, NF-kappabeta RNA) and 16S rDNA in MDD at t1 relative to
      healthy control subjects. These markers showed a significant decrease during CBT
      (t1>t2 in MDD). We observed no between-group differences and changes in the case
      of TLR-2. Greater reduction of pro-inflammatory markers during CBT was associated
      with more pronounced clinical improvement. IL-6 and CRP displayed a moderately
      elevated level in MDD and did not change during CBT. In conclusion, TLR-4
      signaling is up-regulated in newly diagnosed patients with MDD, which may be
      related to bacterial translocation or to the presence of various damage
      associated molecular patterns. Clinical improvement during psychotherapy is
      associated with decreased expression of pro-inflammatory markers. 

PMID- 24726794
TI  - Successful salvage of complicated calcaneal blastomycosis in disseminated disease
      with staged surgical reconstruction and local-systemic antifungal therapy.
AB  - Disseminated blastomycosis can be a devastating disease, affecting multiple organ
      systems, including the musculoskeletal system. Osteomyelitis from disseminated
      disease can be difficult to eradicate but is particularly important to
      successfully manage in the load-bearing bones of the lower extremity. We present
      a staged protocol for salvage of blastomycotic calcaneal osteomyelitis in the
      presence of disseminated disease. 

PMID- 24726795
TI  - Glomangiomatosis concentrated in the ankle with varied appearances: a case
      report.
AB  - Glomangiomatosis is an exceedingly rare condition. This report details a case of
      multiple glomangiomas concentrated in the ankle of a 59-year-old male. Despite
      identical histological findings, the lesions displayed varied clinical features
      at physical examination, at magnetic resonance imaging, and upon further
      examination after excision. Unlike solitary glomus tumors, glomangiomas can vary
      widely in clinical appearance. 

PMID- 24726796
TI  - Experimental observation of cumulative second-harmonic generation of lamb waves
      propagating in long bones.
AB  - The experimental observation of cumulative second-harmonic generation of
      fundamental Lamb waves in long bones is reported. Based on the modal expansion
      approach to waveguide excitation and the dispersion characteristics of Lamb waves
      in long bones, the mechanism underlying the generation and accumulation of second
      harmonics by propagation of the fundamental Lamb waves was investigated. An
      experimental setup was established to detect the second-harmonic signals of Lamb
      wave propagation in long bones in vitro. Through analysis of the group velocities
      of the received signals, the appropriate fundamental Lamb wave modes and the
      duration of the second-harmonic signals could be identified. The integrated
      amplitude of the time-domain second-harmonic signal was introduced and used to
      characterize the efficiency of second-harmonic generation by fundamental Lamb
      wave propagation. The results indicate that the second-harmonic signal generated
      by fundamental Lamb waves propagating in long bones can be observed clearly, and
      the effect was cumulative with propagation distance when the fundamental Lamb
      wave mode and the double-frequency Lamb wave mode had the same phase velocities.
      The present results may be important in the development of a new method to
      evaluate the status of long bones using the cumulative second harmonic of
      ultrasonic Lamb waves.

PMID- 24726797
TI  - Performance of phalangeal quantitative ultrasound parameters in the evaluation of
      reduced bone mineral density assessed by DX in patients with 21 hydroxylase
      deficiency.
AB  - The purpose of this study was to verify the performance of quantitative
      ultrasound (QUS) parameters of proximal phalanges in the evaluation of reduced
      bone mineral density (BMD) in patients with congenital adrenal hyperplasia due to
      21-hydroxylase deficiency (21 OHD). Seventy patients with 21 OHD (41 females and
      29 males), aged between 6-27 y were assessed. The QUS measurements, amplitude
      dependent speed of sound (AD-SoS), bone transmission time (BTT), and ultrasound
      bone profile index (UBPI) were obtained using the BMD Sonic device (IGEA, Carpi,
      Italy) on the last four proximal phalanges in the non-dominant hand. BMD was
      determined by dual energy X-ray (DXA) across the total body and lumbar spine
      (LS). Total body and LS BMD were positively correlated to UBPI, BTT and AD-SoS
      (correlation coefficients ranged from 0.59-0.72, p < 0.001). In contrast, when
      comparing patients with normal and low (Z-score < -2) BMD, no differences were
      found in the QUS parameters. Furthermore, UBPI, BTT and AD-SoS measurements were
      not effective for diagnosing patients with reduced BMD by receiver operator
      characteristic curve parameters. Although the AD-SoS, BTT and UBPI showed
      significant correlations with the data obtained by DXA, they were not effective
      for diagnosing reduced bone mass in patients with 21 OHD.

PMID- 24726798
TI  - Measurement of corneal elasticity with an acoustic radiation force elasticity
      microscope.
AB  - To investigate the role of collagen structure in corneal biomechanics,
      measurement of localized corneal elasticity with minimal destruction to the
      tissue is necessary. We adopted the recently developed acoustic radiation force
      elastic microscopy (ARFEM) technique to measure localize biomechanical properties
      of the human cornea. In ARFEM, a low-frequency, high-intensity acoustic force is
      used to displace a femtosecond laser-generated microbubble, while high-frequency,
      low-intensity ultrasound is used to monitor the position of the microbubble
      within the cornea. Two ex vivo human corneas from a single donor were dehydrated
      to physiologic thickness, embedded in gelatin and then evaluated using the ARFEM
      technique. In the direction perpendicular to the corneal surface, ARFEM
      measurements provided elasticity values of E = 1.39 +/- 0.28 kPa for the central
      anterior cornea and E = 0.71 +/- 0.21 kPa for the central posterior cornea in
      pilot studies. The increased value of corneal elasticity in the anterior cornea
      correlates with the higher density of interweaving lamellae in this region.

PMID- 24726799
TI  - Reproducibility of two 3-D ultrasound carotid plaque quantification methods.
AB  - Compared with single 2-D images, emerging 3-D ultrasound technologies hold the
      promise of reducing variability and increasing sensitivity in the quantification
      of carotid plaques for individual cardiovascular risk stratification. Inter- and
      intra-observer agreement between a manual, cross-sectional, 2-D freehand sweep
      and a mechanical 3-D ultrasound investigation of 62 carotid artery plaques is
      reported with intra-class correlation coefficients (with 95% confidence
      intervals). Inter-observer agreement was 0.60 (0.29-0.77) for the freehand method
      and 0.89 (0.83-0.93) for the mechanical 3-D acquisition. The use of semi
      automated computerized planimetric measurements of plaque burden has high intra
      observer repeatability, but is vulnerable to systematic inter-observer
      differences. For the 2-D freehand sweep, a considerable contribution to variation
      is introduced by the scanning procedure itself, that is, the lack of controlled
      motion along the third dimension. Future implementation of 3-D ultrasound
      quantification in large-scale studies of inter-individual cardiovascular risk
      assessment seems justified using the methods described.

PMID- 24726800
TI  - Scatterer number density considerations in reference phantom-based attenuation
      estimation.
AB  - Attenuation estimation and imaging have the potential to be a valuable tool for
      tissue characterization, particularly for indicating the extent of thermal
      ablation therapy in the liver. Often the performance of attenuation estimation
      algorithms is characterized with numerical simulations or tissue-mimicking
      phantoms containing a high scatterer number density (SND). This ensures an
      ultrasound signal with a Rayleigh distributed envelope and a signal-to-noise
      ratio (SNR) approaching 1.91. However, biological tissue often fails to exhibit
      Rayleigh scattering statistics. For example, across 1647 regions of interest in
      five ex vivo bovine livers, we obtained an envelope SNR of 1.10 +/- 0.12 when the
      tissue was imaged with the VFX 9L4 linear array transducer at a center frequency
      of 6.0 MHz on a Siemens S2000 scanner. In this article, we examine attenuation
      estimation in numerical phantoms, tissue-mimicking phantoms with variable SNDs
      and ex vivo bovine liver before and after thermal coagulation. We find that
      reference phantom-based attenuation estimation is robust to small deviations from
      Rayleigh statistics. However, in tissue with low SNDs, large deviations in
      envelope SNR from 1.91 lead to subsequently large increases in attenuation
      estimation variance. At the same time, low SND is not found to be a significant
      source of bias in the attenuation estimate. For example, we find that the
      standard deviation of attenuation slope estimates increases from 0.07 to 0.25
      dB/cm-MHz as the envelope SNR decreases from 1.78 to 1.01 when estimating
      attenuation slope in tissue-mimicking phantoms with a large estimation kernel
      size (16 mm axially * 15 mm laterally). Meanwhile, the bias in the attenuation
      slope estimates is found to be negligible (<0.01 dB/cm-MHz). We also compare
      results obtained with reference phantom-based attenuation estimates in ex vivo
      bovine liver and thermally coagulated bovine liver.

PMID- 24726802
TI  - Discovery and SAR of novel tetrahydropyrrolo[3,4-c]pyrazoles as inhibitors of the
      N-type calcium channel.
AB  - A novel series of substituted tetrahydropyrrolo[3,4-c]pyrazoles were investigated
      as blockers of the N-type calcium channel (Cav2.2 channels), a chronic pain
      target. 

PMID- 24726801
TI  - Cloning of circadian rhythmic pathway genes and perturbation of oscillation
      patterns in endocrine disrupting chemicals (EDCs)-exposed mangrove killifish
      Kryptolebias marmoratus.
AB  - To investigate the effect of endocrine disrupting chemicals (EDCs) on the
      circadian rhythm pathway, we cloned clock and circadian rhythmic pathway
      associated genes (e.g. Per2, Cry1, Cry2, and BMAL1) in the self-fertilizing
      mangrove killifish Kryptolebias marmoratus. The promoter region of Km-clock had 1
      aryl hydrocarbon receptor element (AhRE, GTGCGTGACA) and 8 estrogen receptor (ER)
      half-sites, indicating that the AhRE and ER half sites would likely be associated
      with regulation of clock protein activity during EDCs-induced cellular stress.
      The Km-clock protein domains (bHLH, PAS1, PAS2) were highly conserved in five
      additional fish species (zebrafish, Japanese medaka, Southern platyfish, Nile
      tilapia, and spotted green pufferfish), suggesting that the fish clock protein
      may play an important role in controlling endogenous circadian rhythms. The
      promoter regions of Km-BMAL1, -Cry1, -Cry2, and -Per2 were found to contain
      several xenobiotic response elements (XREs), indicating that EDCs may be able to
      alter the expression of these genes. To analyze the endogenous circadian rhythm
      in K. marmoratus, we measured expression of Km-clock and other circadian rhythmic
      genes (e.g. Per2, Cry1, Cry2, and BMAL1) in different tissues, and found
      ubiquitous expression, although there were different patterns of transcript
      amplification during different developmental stages. In an estrogen (E2)-exposed
      group, Km-clock expression was down-regulated, however, a hydroxytamoxifen (TMX,
      nonsteroid estrogen antagonist)-exposed group showed an upregulated pattern of Km
      clock expression, suggesting that the expression of Km-clock is closely
      associated with exposure to EDCs. In response to the exposure of bisphenol A
      (BPA) and 4-tert-octyphenol (OP), Km-clock expression was down-regulated in the
      pituitary/brain, muscle, and skin in both gender types (hermaphrodite and
      secondary male). In juvenile K. marmoratus liver tissue, expression of Km-clock
      and other circadian rhythmic pathway-associated genes showed a regular
      oscillation pattern over a period of approximately 24h during a 12L:12D cycle.
      However, the circadian rhythm of BPA-exposed juvenile K. marmoratus liver tissue
      was perturbed over a 12L:12D period. This study will aid in our understanding of
      how EDCs perturb endogenous circadian rhythms, particularly in BPA-exposed fish
      liver tissue. 

PMID- 24726803
TI  - Discovery and SAR of a novel series of 2,4,5,6-tetrahydrocyclopenta[c]pyrazoles
      as N-type calcium channel inhibitors.
AB  - A novel series of substituted 2,4,5,6-tetrahydrocyclopenta[c]pyrazoles were
      investigated as N-type calcium channel blockers (Cav2.2 channels), a chronic pain
      target. One compound was active in vivo in the rat CFA pain model.

PMID- 24726804
TI  - Design, synthesis, ADME characterization and antileishmanial evaluation of novel
      substituted quinoline analogs.
AB  - In vitro ADME characterization of the lead compound 1 identified for visceral
      leishmaniasis was undertaken and further structural analogs were synthesized for
      antileishmanial screening. Compound 1 was highly permeable in intestinal PAMPA
      model (31 * 10(-6)cm/s) and was moderately bound to mouse and human plasma
      proteins (% bound 85-95%), its blood to plasma concentration ratio was less than
      1, but the compound was unstable in blood. Compound 1 was found to have no CYP450
      liability with CYP2C9, 2C19, 2D6 and 3A4. It showed inhibition with CYP1A2 with
      an IC50 value of 0.50 MUM. Analogs of 1 were synthesized and subsequently
      characterized for in vitro activity against the intracellular form of Leishmania
      donovani. Resulting quinolines were found to have similar efficacy as 1 against
      the parasite. Compounds 8b and 8f were found to be the most active with IC50
      values of 0.84 MUM and 0.17 MUM, respectively compared to 0.22 MUM for compound
      1. Of all the analogs tested, 8d was stable in hamster, mouse and human liver
      microsomes but lost the efficacy with an IC50 of 6.42 MUM. Based on the in vitro
      efficacy and DMPK profile, compounds 8b and 8f seem the best candidates to be
      screened in further assays.

PMID- 24726805
TI  - Identification and optimization of indolo[2,3-c]quinoline inhibitors of IRAK4.
AB  - IRAK4 is responsible for initiating signaling from Toll-like receptors (TLRs) and
      members of the IL-1/18 receptor family. Kinase-inactive knock-ins and targeted
      deletions of IRAK4 in mice cause reductions in TLR induced pro-inflammatory
      cytokines and these mice are resistant to various models of arthritis. Herein we
      report the identification and optimization of a series of potent IRAK4
      inhibitors. Representative examples from this series showed excellent selectivity
      over a panel of kinases, including the kinases known to play a role in TLR
      mediated signaling. The compounds exhibited low nM potency in LPS- and R848
      induced cytokine assays indicating that they are blocking the TLR signaling
      pathway. A key compound (26) from this series was profiled in more detail and
      found to have an excellent pharmaceutical profile as measured by predictive
      assays such as microsomal stability, TPSA, solubility, and clogP. However, this
      compound was found to afford poor exposure in mouse upon IP or IV administration.
      We found that removal of the ionizable solubilizing group (32) led to increased
      exposure, presumably due to increased permeability. Compounds 26 and 32, when
      dosed to plasma levels corresponding to ex vivo whole blood potency, were shown
      to inhibit LPS-induced TNFalpha in an in vivo murine model. To our knowledge,
      this is the first published in vivo demonstration that inhibition of the IRAK4
      pathway by a small molecule can recapitulate the phenotype of IRAK4 knockout
      mice.

PMID- 24726806
TI  - Syk inhibitors with high potency in presence of blood.
AB  - We describe two series of Syk inhibitors which potently abrogate Syk kinase
      function in enzymatic assays, cellular assays and in primary cells in the
      presence of blood. Introduction of a 7-aminoindole substituent led to derivatives
      with good kinase selectivity and little or no hERG channel inhibition (3b, 10c). 

PMID- 24726807
TI  - Scaffold hopping approach to a new series of smoothened antagonists.
AB  - The hedgehog (Hh) signaling pathway is a key regulator during embryonic
      development, while in adults, it has limited functions such as stem cell
      maintenance and tissue repair. The aberrant activity of the Hh signaling in
      adults has been linked to numerous human cancers. Inhibition of Hh signaling
      therefore represents a promising approach toward novel anticancer therapies. The
      Smoothened (Smo) receptor mediates Hh signaling. Here we report a new series of
      Smo antagonists which were obtained by a scaffold hopping strategy. Compounds
      from this new scaffold demonstrated decent inhibition of Hh pathway signaling.
      The new scaffold can serve as a starting point for further optimization. 

PMID- 24726808
TI  - Novel synthesis of nitro-quinoxalinone derivatives as aldose reductase
      inhibitors.
AB  - A novel, non-acid series of nitroquinoxalinone derivatives was synthesized and
      tested for their inhibitory activity against aldose reductase as targeting
      enzyme. All active compounds displayed an 8-nitro group, and showed significant
      activity in IC50 values ranging from 1.54 to 18.17 MUM. Among them 6,7-dichloro
      5,8-dinitro-3-phenoxyquinoxalin-2(1H)-one (7e), exhibited the strongest aldose
      reductase activity with an IC50 value of 1.54 MUM and a good SAR (structure
      activity relationship) profile.

PMID- 24726809
TI  - Design, synthesis and biological evaluation of benzylisoquinoline derivatives as
      multifunctional agents against Alzheimer's disease.
AB  - A novel series of benzylisoquinoline derivatives were designed, synthesized, and
      evaluated as multifunctional agents against Alzheimer's disease (AD). The
      screening results showed that most of the compounds significantly inhibited
      cholinesterases (ChEs), human cholinesterases (h-ChEs) and self-induced beta
      amyloid (Abeta) aggregation. In particular, compound 9k showed the strongest
      acetylcholinesterase (AChE) inhibitory activity, being 1000-fold and 3-fold more
      potent than its precursor benzylisoquinoline (10) and the positive control
      galanthamine, respectively. In addition, 9k was a moderately potent inhibitor for
      h-ChEs. Compared with precursor benzylisoquinoline (36.0% at 20MUM), 9k (78.4% at
      20MUM) could further inhibit Abeta aggregation. Moreover, 9k showed low cell
      toxicity in human SH-SY5Y neuroblastoma cells. Therefore, compound 9k might be a
      promising lead compound for AD treatment. 

PMID- 24726810
TI  - Combined mechanism of refractory shock in primary cardiac lymphoma: a rare
      dilemma.
AB  - Primary cardiac lymphoma is very rare, and usually manifests after the fifth
      decade of life. The lack of typical manifestations makes it difficult to diagnose
      at an early stage that can be discovered only by echocardiography. The location
      of the tumour often results in cardiac compromise, which prevents the delivery of
      potentially curative therapies. Clinical presentations may depend on flow
      obstruction, infiltration of adjacent tissues, tumour embolisation, and
      atrioventricular (AV) disturbances. We report a rare case of primary cardiac
      lymphoma that presented with clinical signs of shock from two distinct
      mechanisms. The first mechanism was intermittent complete AV block that was
      caused by disruption of the electrical conduction system from tumour infiltration
      in addition to direct mechanical compression of the atrioventricular node by the
      tumour. The second mechanism, subtotal RV inflow obstruction from the bulky mass
      contributed to compromising venous return, which played a major role of
      refractory shock in this case. 

PMID- 24726811
TI  - Casting a wider fish net on animal models in neuropsychiatric research.
AB  - Neuropsychiatric disorders, such as schizophrenia, are associated with abnormal
      brain development. In this review, we discuss how studying dimensional components
      of these disorders, or endophenotypes, in a wider range of animal models will
      deepen our understanding of how interactions between biological and environmental
      factors alter the trajectory of neurodevelopment leading to aberrant behavior. In
      particular, we discuss some of the advantages of incorporating studies of brain
      and behavior using a range of teleost fish species into current neuropsychiatric
      research. From the perspective of comparative neurobiology, teleosts share a
      fundamental pattern of neurodevelopment and functional brain organization with
      other vertebrates, including humans. These shared features provide a basis for
      experimentally probing the mechanisms of disease-associated brain abnormalities.
      Moreover, incorporating information about how behaviors have been shaped by
      evolution will allow us to better understand the relevance of behavioral
      variation to determine their physiological underpinnings. We believe that
      exploiting the conservation in brain development across vertebrate species, and
      the rich diversity of fish behavior in lab and natural populations will lead to
      significant new insights and a holistic understanding of the neurobiological
      systems implicated in neuropsychiatric disorders. 

PMID- 24726812
TI  - A preliminary study of functional connectivity of medication naive children with
      obsessive-compulsive disorder.
AB  - BACKGROUND: Evidence suggests that obsessive-compulsive disorder (OCD) is
      associated with a dysfunction in the cortico-striatal-thalamic-cortical (CSTC)
      circuitry. Resting state functional connectivity magnetic resonance imaging (rs
      fcMRI) allows measurements of resting state networks (RSNs), brain networks that
      are present at 'rest'. However, although OCD has a typical onset during childhood
      or adolescence, only two other studies have performed rs-fcMRI comparisons of
      RSNs in children and adolescents with OCD against healthy controls. METHODS: In
      the present study, we performed resting state functional magnetic resonance
      imaging using a 3 Tesla MRI, in 11 medication-naive children and adolescents with
      OCD and 9 healthy controls. In contrast to previous studies that relied on a
      priori determination of RSNs, we determined resting state functional connectivity
      with a data-driven independent component analysis (ICA). RESULTS: Consistent with
      previous reports in healthy adults, we identified 13 RSNs. Case-control un
      adjusted statistical significance (p<0.05) was found for two networks. Firstly,
      increased connectivity (OCD>control) in the right section of Brodmann area 43 of
      the auditory network; Secondly, decreased connectivity in the right section of
      Brodmann area 8 and Brodmann area 40 in the cingulate network. CONCLUSIONS: Our
      preliminary findings of case-control differences in RSNs lend further support to
      the CSTC hypothesis of OCD, as well as implicating other regions of the brain
      outside of the CSTC.

PMID- 24726814
TI  - Mental health utilization of new-to-care Iraq and Afghanistan Veterans following
      suicidal ideation assessment.
AB  - We evaluated the impact of brief structured suicidal ideation (SI) assessments on
      mental health care among new-to-care Operations Enduring Freedom and Iraqi
      Freedom (OEF/OIF) veterans. National datasets provided military, demographic, and
      clinical information. For all new-to-care OEF/OIF veterans administered
      depression screens (PHQ-2: Patient Health Questionnaire-2) and structured SI
      assessments in primary care or ambulatory mental health settings of three
      Veterans Affairs (VA) Medical Centers between April 2008 and September 2009
      (N=465), generalized estimating equations were used to examine associations
      between SI and number of subsequent-year specialty mental health visits and
      antidepressant prescriptions. Approximately one-third of the veterans reported
      SI. In multivariate models, PTSD and anxiety diagnoses, severe depression
      symptoms, being married, and SI assessment by a mental health clinician were
      associated with more mental health visits in the subsequent year. Depression,
      PTSD, and anxiety diagnoses, and SI assessment by a mental health clinician were
      associated with receiving antidepressants. Presence of SI did not significantly
      affect subsequent year mental health utilization when adjusting for diagnostic
      and clinician variables, but inaugural visits involving mental health clinicians
      were consistently associated with subsequent mental health care. 

PMID- 24726813
TI  - Circulating alanine transaminase (ALT) and gamma-glutamyl transferase (GGT), but
      not fetuin-A, are associated with metabolic risk factors, at baseline and at two
      year follow-up: the prospective Cyprus Metabolism Study.
AB  - OBJECTIVE: To comparatively evaluate traditional liver tests and fetuin A as
      predictors of cardiometabolic risk, we studied associations between serum alanine
      transaminase (ALT), gamma-glutamyl transferase (GGT), aspartate aminotransferase
      (AST) and fetuin-A and anthropometric, metabolic, and cardiovascular parameters
      cross-sectionally at baseline, and prospectively, after 2-years of follow-up.
      RESEARCH DESIGN AND METHODS: 616 randomly enrolled young healthy participants in
      the Cyprus Metabolism Study, including all 93 subjects who participated in the
      follow-up study 2 years after baseline assessment, were included in this study.
      RESULTS: In the cross-sectional study, serum ALT and GGT were strongly correlated
      with anthropometric, cardiovascular, and metabolic variables, while serum AST was
      only correlated with waist circumference and waist-to-hip ratio. Fetuin-A was
      correlated with anthropometric variables, systolic blood pressure (SBP), insulin,
      and homeostasis model of assessment-insulin resistance (HOMA-IR) in the
      unadjusted model. In the fully adjusted model, both serum ALT and GGT levels
      remained positively correlated with total and low-density lipoprotein (LDL)
      cholesterol. GGT levels also remained correlated with triglycerides. ALT levels
      remained strongly positively correlated with insulin (r=0.17, p<.0001) and HOMA
      IR (r=0.16, p=0.0001). Serum fetuin-A levels were no longer significantly
      correlated with any variables. Prospectively, ALT and GGT were predictors of
      anthropometric variables and LDL cholesterol, while baseline levels of AST and
      fetuin-A were not predictors of any variables at 2-year follow-up. CONCLUSIONS:
      We confirmed associations of ALT and GGT levels but failed to demonstrate an
      independent association between fetuin-A and cardiometabolic risk factors in
      young healthy men. Traditional liver tests (LFTs) are thus better than fetuin-A
      predictors of metabolic risk factors cross-sectionally and prospectively in young
      healthy adults.

PMID- 24726815
TI  - What is the contribution of different cognitive biases and stressful childhood
      events to the presence and number of previous depressive episodes?
AB  - Negative cognitive biases as well as stressful childhood events are well-known
      risk factors for depression. Few studies have compared the association of
      different types of biases and events with depression. The current study examined
      whether different cognitive biases and stressful childhood events variables were
      associated with depression and recurrence. Three types of childhood events were
      assessed in 83 never-depressed and 337 formerly depressed individuals: trauma
      within the family, trauma outside the family, and adverse events. Furthermore,
      after a sad mood induction procedure, participants executed a Dot Probe task
      (selective attentional bias), an Emotional Stroop task (attentional interference
      bias) and an incidental learning task (memory bias). The association of these
      measures with case status and recurrence status (one or multiple past episodes)
      was examined. Negative memory bias and traumatic childhood events within the
      family were associated with case status, whereas none of the bias measures or
      childhood events variables were associated with recurrence status. The results
      indicate that memory bias as well as the experience of aggression and/or abuse
      within the family during childhood are independently associated with depression.
      Biases and stressful childhood events did not offer differentiation between
      individuals with one or multiple past episodes. 

PMID- 24726816
TI  - The probability of association between response inhibition and compulsive
      symptoms of obsessive-compulsive disorder: response to Abramovitch and
      Abramowitz.

PMID- 24726817
TI  - Depression in first episode psychosis: the role of subordination and shame.
AB  - Depression in early psychosis is linked to poor outcome, relapse and risk of
      suicide, yet remains poorly understood. This article aims to examine the
      development of depression in acute and post psychotic phases of first episode
      psychosis (FEP), and its relationship to persecutors, voices, insight, and
      recovery. Data were gathered on 92 patients with acute FEP on depression course,
      severity and experience of positive symptoms, insight and appraisals of illness
      using validated semi-structured interviews and questionnaires. Measures were
      repeated at 12 months. Malevolent voices, use of safety behaviours and
      subordination to persecutors were associated with depression and suicidal
      behaviour in acute FEP. Loss, Shame, low level continuing positive symptoms and
      longer duration of untreated psychosis were associated with post psychotic
      depression. Negative appraisals remained stable despite recovery in other symptom
      domains. Thus, depression and risk in early psychosis may be propagated by the
      personal significance and content of positive symptoms experienced. When in
      recovery, low level symptoms, longer period of illness and negative appraisals
      are significant factors. 

PMID- 24726818
TI  - Associations between specific psychotic symptoms and specific childhood
      adversities are mediated by attachment styles: an analysis of the National
      Comorbidity Survey.
AB  - Accumulated evidence over the past decade consistently demonstrates a
      relationship between childhood adversity and psychosis in adulthood. There is
      some evidence of specific associations between childhood sexual abuse and
      hallucinations, and between insecure attachment and paranoia. Data from the
      National Comorbidity Survey were used in assessing whether current attachment
      styles influenced the association between adverse childhood experiences and
      psychotic symptoms in adulthood. Hallucinations and paranoid beliefs were
      differentially associated with sexual abuse (rape and sexual molestation) and
      neglect, respectively. Sexual abuse and neglect were also associated with
      depression. The relationship between neglect and paranoid beliefs was fully
      mediated via anxious and avoidant attachment. The relationship between sexual
      molestation and hallucinations was independent of attachment style. The
      relationship between rape and hallucinations was partially mediated via anxious
      attachment; however this effect was no longer present when depression was
      included as a mediating variable. The findings highlight the importance of
      addressing and understanding childhood experiences within the context of current
      attachment styles in clinical interventions for patients with psychosis. 

PMID- 24726819
TI  - A systematic review of the ability of urine concentration to distinguish
      antipsychotic- from psychosis-induced hyponatremia.
AB  - Life-threatening hyponatremia in psychotic patients is common and typically is
      attributable to either antipsychotic medication or to acute psychosis in those
      with the polydipsia-hyponatremia syndrome. The preferred treatment for one
      situation may worsen the hyponatremia if caused by the other situation. Hence it
      is critical to distinguish between these two possibilities. Case reports and
      series were identified through electronic databases. Fifty-four cases of
      hyponatremia without recognized causes in psychotic patients were divided into
      those with dilute (<plasma osmolality) or concentrated (>plasma osmolality)
      urine. The distribution of urine concentration and measures likely to be
      associated with psychotic illness and its treatment were compared in both groups.
      Naranjo's scale was utilized to determine the probability hyponatremia was drug
      induced. Urine osmolality fit a bimodal distribution (intersection 219mOsm/kg)
      better than a unimodal distribution. 'Probable' drug-induced cases occurred 6.8
      (95%CI=1.6-28.9) times more often in those with concentrated urine. Acute
      psychotic exacerbations occurred 4.5 (95%CI=0.4-54.1) times more often in those
      with dilute urine. These findings, as well as several other trends in the data,
      indicate that measures of urine concentration can help distinguish between
      antipsychotic-induced and psychosis-induced hyponatremia. 

PMID- 24726821
TI  - Evaluating the toxicity of food processing wastes as co-digestion substrates with
      dairy manure.
AB  - Studies have shown that including food waste as a co-digestion substrate in the
      anaerobic digestion of livestock manure can increase energy production. However,
      the type and inclusion rate of food waste used for co-digestion need to be
      carefully considered in order to prevent adverse conditions in the digestion
      environment. This study determined the effect of increasing the concentration
      (2%, 5%, 15% and 30%, by volume) of four food-processing wastes (meatball,
      chicken, cranberry and ice cream processing wastes) on methane production.
      Anaerobic toxicity assay (ATA) and specific methanogenic activity (SMA) tests
      were conducted to determine the concentration at which each food waste became
      toxic to the digestion environment. Decreases in methane production were observed
      at concentrations above 5% for all four food waste substrates, with up to 99%
      decreases in methane production at 30% food processing wastes (by volume). 

PMID- 24726822
TI  - Recycling of non-metallic fractions from waste electrical and electronic
      equipment (WEEE): a review.
AB  - The world's waste electrical and electronic equipment (WEEE) consumption has
      increased incredibly in recent decades, which have drawn much attention from the
      public. However, the major economic driving force for recycling of WEEE is the
      value of the metallic fractions (MFs). The non-metallic fractions (NMFs), which
      take up a large proportion of E-wastes, were treated by incineration or landfill
      in the past. NMFs from WEEE contain heavy metals, brominated flame retardant
      (BFRs) and other toxic and hazardous substances. Combustion as well as landfill
      may cause serious environmental problems. Therefore, research on resource
      reutilization and safe disposal of the NMFs from WEEE has a great significance
      from the viewpoint of environmental protection. Among the enormous variety of
      NMFs from WEEE, some of them are quite easy to recycle while others are
      difficult, such as plastics, glass and NMFs from waste printed circuit boards
      (WPCBs). In this paper, we mainly focus on the intractable NMFs from WEEE.
      Methods and technologies of recycling the two types of NMFs from WEEE, plastics,
      glass are reviewed in this paper. For WEEE plastics, the pyrolysis technology has
      the lowest energy consumption and the pyrolysis oil could be obtained, but the
      containing of BFRs makes the pyrolysis recycling process problematic.
      Supercritical fluids (SCF) and gasification technology have a potentially smaller
      environmental impact than pyrolysis process, but the energy consumption is
      higher. With regard to WEEE glass, lead removing is requisite before the
      reutilization of the cathode ray tube (CRT) funnel glass, and the recycling of
      liquid crystal display (LCD) glass is economically viable for the containing of
      precious metals (indium and tin). However, the environmental assessment of the
      recycling process is essential and important before the industrialized production
      stage. For example, noise and dust should be evaluated during the glass cutting
      process. This study could contribute significantly to understanding the recycling
      methods of NMFs from WEEE and serve as guidance for the future technology
      research and development.

PMID- 24726820
TI  - Cell signaling during development of Dictyostelium.
AB  - Continuous communication between cells is necessary for development of any
      multicellular organism and depends on the recognition of secreted signals. A wide
      range of molecules including proteins, peptides, amino acids, nucleic acids,
      steroids and polylketides are used as intercellular signals in plants and
      animals. They are also used for communication in the social ameba Dictyostelium
      discoideum when the solitary cells aggregate to form multicellular structures.
      Many of the signals are recognized by surface receptors that are seven
      transmembrane proteins coupled to trimeric G proteins, which pass the signal on
      to components within the cytoplasm. Dictyostelium cells have to judge when
      sufficient cell density has been reached to warrant transition from growth to
      differentiation. They have to recognize when exogenous nutrients become limiting,
      and then synchronously initiate development. A few hours later they signal each
      other with pulses of cAMP that regulate gene expression as well as direct
      chemotactic aggregation. They then have to recognize kinship and only continue
      developing when they are surrounded by close kin. Thereafter, the cells diverge
      into two specialized cell types, prespore and prestalk cells, that continue to
      signal each other in complex ways to form well proportioned fruiting bodies. In
      this way they can proceed through the stages of a dependent sequence in an
      orderly manner without cells being left out or directed down the wrong path.

PMID- 24726823
TI  - Alzheimer's disease, enzyme targets and drug discovery struggles: from natural
      products to drug prototypes.
AB  - Alzheimer's disease (AD) is an incapacitating neurodegenerative disease that
      slowly destroys brain cells. This disease progressively compromises both memory
      and cognition, culminating in a state of full dependence and dementia. Currently,
      AD is the main cause of dementia in the elderly and its prevalence in the
      developed world is increasing rapidly. Classic drugs, such as
      acetylcholinesterase inhibitors (AChEIs), fail to decline disease progression and
      display several side effects that reduce patient's adhesion to pharmacotherapy.
      The past decade has witnessed an increasing focus on the search for novel AChEIs
      and new putative enzymatic targets for AD, like beta- and gamma-secretases,
      sirtuins, caspase proteins and glycogen synthase kinase-3 (GSK-3). In addition,
      new mechanistic rationales for drug discovery in AD that include autophagy and
      synaptogenesis have been discovered. Herein, we describe the state-of-the-art of
      the development of recent enzymatic inhibitors and enhancers with therapeutic
      potential on the treatment of AD. 

PMID- 24726824
TI  - Cancer patient survival in Estonia 1995-2009: time trends and data quality.
AB  - BACKGROUND: Survival from most cancers in Estonia has been consistently below
      European average. The objective of this study was to examine recent survival
      trends in Estonia and to quantify the effect on survival estimates of the
      temporary disruption of the Estonian Cancer Registry (ECR) practices in 2001-2007
      when death certificates could not be used for case ascertainment. PATIENTS AND
      METHODS: ECR data on all adult cases of 16 common cancers diagnosed in Estonia
      during 1995-2008 and followed up for vital status until 2009 were used to
      estimate relative survival ratios (RSR). We used cohort analysis for patients
      diagnosed in 1995-1999 and 2000-2004; and period hybrid approach to obtain the
      most recent estimates (2005-2009). We compared five-year RSRs calculated from
      data sets with and without death certificate initiated (DCI) cases. RESULTS: A
      total of 64328 cancer cases were included in survival analysis. Compared with
      1995-1999, five-year age-standardized RSR increased 20 percent units for prostate
      cancer, reaching 76% in 2005-2009. A rise of 10 percent units or more was also
      seen for non-Hodgkin lymphoma (five-year RSR 51% in 2005-2009), and cancers of
      rectum (49%), breast (73%) and ovary (37%). The effect of including/excluding DCI
      cases from survival analysis was small except for lung and pancreatic cancers.
      CONCLUSIONS: Relative survival continued to increase in Estonia during the first
      decade of the 21st century, although for many cancers, a gap between Estonia and
      more affluent countries still exists. Cancer control efforts should aim at the
      reduction of risk factors amenable to primary prevention, but also at the
      improvement of early diagnosis and ensuring timely and optimal care to all cancer
      patients.

PMID- 24726825
TI  - Total body fat and the risk of Barrett's oesophagus - a bioelectrical impedance
      study.
AB  - BACKGROUND: Body mass index is associated with the risk of Barrett's oesophagus
      (BO). It is uncertain whether this is related to total body fat or other factors
      that correlate with body mass index. We aimed to quantify the association between
      total body fat (measured by bioelectrical impedance) and risk of BO and examine
      if this association was modified by gastro-oesophageal reflux (GOR) and abdominal
      obesity. METHODS: In 2007-2009, we surveyed 235 cases (69% Males, Mean age 62.1
      years) and 244 age and sex matched population controls from a population based
      case-control study of BO. We conducted structured interviews, standard
      anthropometry and bioimpedance analysis of total body fat. Odds ratios (OR) and
      95% confidence intervals (CI) were estimated using multivariable logistic
      regression analysis. RESULTS: There was a significantly increased risk of BO
      among those in the highest tertile of total body fat weight (OR 2.01; 95%CI 1.26
      3.21) and total body fat percentage (OR 1.86; 95%CI 1.10-3.15). These risks were
      largely attenuated after adjustment for GOR and waist circumference. There was a
      significantly increased risk of BO among those in the highest tertile of waist
      circumference (OR 2.21; 95%CI 1.39-3.51) and this was minimally attenuated after
      adjustment for total body fat and moderately attenuated after adjustment for GOR.
      CONCLUSIONS: Total body fat is associated with an increased risk of BO but this
      appears to be mediated via both abdominal obesity and GOR. These findings provide
      evidence that abdominal obesity is more important than total body fat in the
      development of BO.

PMID- 24726826
TI  - Novel experimental model of enlarging abdominal aortic aneurysm in rabbits.
AB  - OBJECTIVE: This study tested the hypothesis that an experimental model of
      abdominal aortic aneurysm in rabbits results in progressive enlargement when
      induced by a combination of periaortic elastase administration and aortic
      coarctation. METHODS: Male New Zealand white rabbits were randomly divided into
      four groups: (A) stenosis (n = 12), (B) elastase (n = 12), (C) aneurysm (n = 15),
      and (D) control (n = 12). The stenosis group received an extrinsic coarctation
      below the right renal artery, the elastase group received a 10-minute
      administration of 60 MUL elastase (1 U/MUL) in a 1.5-cm aortic segment, the
      aneurysm group received stenosis and elastase, and a sham operation was performed
      in the control group. The aortic diameter was measured after 1, 2, 4, 8, and 16
      weeks, and animals were subsequently euthanized for histopathologic and
      immunohistochemical studies. RESULTS: All animals in the aneurysm group developed
      aneurysm by 2 weeks after treatment, with average diameters of 5.21 +/- 0.74 mm
      by 2 weeks, 6.23 +/- 1.10 mm by 4 weeks, 7.87 +/- 0.50 mm by 8 weeks, and 9.40 +/
      0.36 mm by 16 weeks. Aortic diameter dilated progressively, and all aneurysms
      developed by 4 weeks in the stenosis group (4.17 +/- 0.22 mm). Only one aneurysm
      was seen in the elastase group by week 1 (3.60 +/- 0.64 mm), and no aneurysm
      formed in the control group by week 8 (2.47 +/- 0.38 mm). The aneurysm group
      exhibited less media thickness, elastin content, and endothelial recovery, but
      stronger expression of matrix metalloproteinase 2 and 9 and rabbit macrophage
      compared with the control group. CONCLUSIONS: This novel rabbit abdominal aortic
      aneurysm model with a gradually enlarging diameter is simply and reliably
      induced, appropriately mimicking human aortic aneurysm disease.

PMID- 24726827
TI  - Predictive scoring model of mortality after surgical or endovascular
      revascularization in patients with critical limb ischemia.
AB  - OBJECTIVE: The latest guideline points to life expectancy of <2 years as the main
      determinant in revascularization modality selection (bypass surgery [BSX] or
      endovascular therapy [EVT]) in patients with critical limb ischemia (CLI). This
      study examined predictors and a predictive scoring model of 2-year mortality
      after revascularization. METHODS: We performed Cox proportional hazards
      regression analysis of data in a retrospective database, the Bypass and
      Endovascular therapy Against Critical limb ischemia from Hyogo (BEACH) registry,
      of 459 consecutive CLI patients who underwent revascularization (396 EVT and 63
      BSX cases between January 2007 and December 2011) to determine predictors of 2
      year mortality. The predictive performance of the score was assessed with the
      area under the time-dependent receiver operating characteristic curve. RESULTS:
      Of 459 CLI patients (mean age, 72 +/- 10 years; 64% male; 49% nonambulatory
      status, 68% diabetes mellitus, 47% on regular dialysis, and 18% rest pain and 82%
      tissue loss as treatment indication), 84 died within 2 years after
      revascularization. In a multivariate model, age >75 years (hazard ratio [HR],
      1.77; 95% confidence interval [CI], 1.10-2.85), nonambulatory status (HR, 5.32;
      95% CI, 2.96-9.56), regular dialysis (HR, 1.90; 95% CI, 1.10-3.26), and ejection
      fraction <50% (HR, 2.49; 95% CI, 1.48-4.20) were independent predictors of 2-year
      mortality. The area under the time-dependent receiver operating characteristic
      curve for the developed predictive BEACH score was 0.81 (95% CI, 0.76-0.86).
      CONCLUSIONS: Predictors of 2-year mortality after EVT or BSX in CLI patients
      included age >75 years, nonambulatory status, regular dialysis, and ejection
      fraction <50%. The BEACH score derived from these predictors allows risk
      stratification of CLI patients undergoing revascularization.

PMID- 24726828
TI  - Divergent signaling mechanisms for venous versus arterial contraction as revealed
      by endothelin-1.
AB  - OBJECTIVE: Venous function is underappreciated in its role in blood pressure
      determination, a physiologic parameter normally ascribed to changes in arterial
      function. Significant evidence points to the hormone endothelin-1 (ET-1) as being
      important to venous contributions to blood pressure. We hypothesized that the
      artery and vein should similarly depend on the signaling pathways stimulated by
      ET-1, specifically phospholipase C (PLC) activation. This produces two functional
      arms of signaling: diacylglycerol (DAG; protein kinase C [PKC] activation) and
      inositol trisphosphate (IP3) production (intracellular calcium release). METHODS:
      The model was the male Sprague-Dawley rat. Isolated tissue baths were used to
      measure isometric contraction. Western blot and immunocytochemical analyses
      measured the magnitude of expression and site of expression, respectively, of IP3
      receptors in smooth muscle/tissue. Pharmacologic methods were used to modify PLC
      activity and signaling elements downstream of PLC (IP3 receptors, PKC). RESULTS:
      ET-1-induced contraction was PLC dependent in both tissues as the PLC inhibitor U
      73122 significantly reduced contraction in aorta (86% +/- 4% of control; P < .05)
      and vena cava (49% +/- 11% of control; P < .05). However, ET-1-induced
      contraction was not significantly inhibited by the IP3 receptor inhibitor 2
      aminoethoxydiphenylborane (100 MUM) in vena cava (82% +/- 8% of control; P = .23)
      but was in the aorta (55% +/- 4% of control; P < .05). All three IP3 receptor
      isoforms were located in venous smooth muscle. IP3 receptors were functional in
      both tissues as the novel membrane-permeable IP3 analogue (Bt-IP3; 10 MUM)
      contracted aorta and vena cava. Similarly, whereas the PKC inhibitor
      chelerythrine (10 MUM) attenuated ET-1-induced contraction in vena cava and aorta
      (5% +/- 2% and 50% +/- 5% of control, respectively; P < .05), only the vena cava
      contracted to the DAG analogue 1-oleoyl-2-acetyl-sn-glycerol. CONCLUSIONS: These
      findings suggest that ET-1 activates PLC in aorta and vena cava, but vena cava
      contraction to ET-1 may be largely IP3 independent. Rather, DAG-not IP3-may
      contribute to contraction to ET-1 in vena cava, in part by activation of PKC.
      These studies outline a fundamental difference between venous and arterial smooth
      muscle and further reinforce a heterogeneity of vascular smooth muscle function
      that could be taken advantage of for therapeutic development.

PMID- 24726829
TI  - Predictive value of negative initial postoperative imaging after endovascular
      aortic aneurysm repair.
AB  - OBJECTIVE: The risk of endoleak and reintervention after endovascular abdominal
      aortic aneurysm repair necessitates lifelong surveillance, which has associated
      costs, radiation exposure, and risk of nephrotoxicity. The best imaging method
      and timing of surveillance remain controversial. We sought to determine if a
      negative result of first postoperative imaging by computed tomography (CT) scan
      was predictive of decreased need for reintervention. We hypothesized that initial
      negative postoperative imaging could identify a low-risk cohort of patients who
      could be observed less frequently. METHODS: Retrospective review of prospectively
      collected institutional outcomes data (2004-2009) included stratification
      according to postoperative imaging results. Baseline characteristics and aneurysm
      morphology were compared between the two groups. Cox regression analysis was used
      to identify risk factors predictive for endoleak-related reintervention. Kaplan
      Meier survival curves were used to plot freedom from all-cause reintervention and
      endoleak-related reintervention for the two groups. RESULTS: A total of 134
      patients were included in the analysis. A total of 107 patients (80%) had
      negative initial postoperative imaging, whereas 27 patients (20%) had evidence of
      an endoleak. There were no significant differences between the two groups in
      terms of comorbidities or anticoagulation status. Kaplan-Meier survival curves
      showed that there was a significant difference between those patients who had a
      negative initial CT scan and those who had a positive scan for endoleak in terms
      of both overall reintervention rates and leak-related reintervention rates.
      Endoleak on the first postoperative CT scan was associated with a hazard ratio of
      6.37 (confidence interval, 2.02-20.10; P = .002) for leak-related reintervention
      and a hazard ratio of 6.01 (confidence interval, 2.24-16.17; P < .001) for all
      cause reintervention. CONCLUSIONS: Patients with negative initial postoperative
      imaging were significantly less likely to require repeated interventions. These
      data suggest that these patients are candidates for less rigorous screening
      protocols.

PMID- 24726830
TI  - Synthetic interaction between the TipN polarity factor and an AcrAB-family efflux
      pump implicates cell polarity in bacterial drug resistance.
AB  - Quinolone antibiotics are clinically important drugs that target bacterial DNA
      replication and chromosome segregation. Although the AcrAB-family efflux pumps
      generally protect bacteria from such drugs, the physiological role of these
      efflux systems and their interplay with other cellular events are poorly
      explored. Here, we report an intricate relationship between antibiotic resistance
      and cell polarity in the model bacterium Caulobacter crescentus. We show that a
      polarity landmark protein, TipN, identified by virtue of its ability to direct
      flagellum placement to the new cell pole, protects cells from toxic misregulation
      of an AcrAB efflux pump through a cis-encoded nalidixic acid-responsive
      transcriptional repressor. Alongside the importance of polarity in promoting the
      inheritance and activity of virulence functions including motility, we can now
      ascribe to it an additional role in drug resistance that is distinct from
      classical efflux mechanisms. 

PMID- 24726831
TI  - VX-809 and related corrector compounds exhibit secondary activity stabilizing
      active F508del-CFTR after its partial rescue to the cell surface.
AB  - The most common mutation causing cystic fibrosis (CF), F508del, impairs
      conformational maturation of CF transmembrane conductance regulator (CFTR),
      thereby reducing its functional expression on the surface of epithelia. Corrector
      compounds including C18 (VRT-534) and VX-809 have been shown to partially rescue
      misfolding of F508del-CFTR and to enhance its maturation and forward trafficking
      to the cell surface. Now, we show that there is an additional action conferred by
      these compounds beyond their role in improving the biosynthetic assembly. In
      vitro studies show that these compounds bind directly to the metastable, full
      length F508del-CFTR channel. Cell culture and patient tissue-based assays confirm
      that in addition to their cotranslational effect on folding, certain corrector
      compounds bind to the full-length F508del-CFTR after its partial rescue to the
      cell surface to enhance its function. These findings may inform the development
      of alternative compounds with improved therapeutic efficacy. 

PMID- 24726832
TI  - Reprogramming acyl carrier protein interactions of an Acyl-CoA promiscuous trans
      acyltransferase.
AB  - Protein interactions between acyl carrier proteins (ACPs) and trans-acting
      acyltransferase domains (trans-ATs) are critical for regioselective extender unit
      installation by many polyketide synthases, yet little is known regarding the
      specificity of these interactions, particularly for trans-ATs with unusual
      extender unit specificities. Currently, the best-studied trans-AT with nonmalonyl
      specificity is KirCII from kirromycin biosynthesis. Here, we developed an assay
      to probe ACP interactions based on leveraging the extender unit promiscuity of
      KirCII. The assay allows us to identify residues on the ACP surface that
      contribute to specific recognition by KirCII. This information proved sufficient
      to modify a noncognate ACP from a different biosynthetic system to be a substrate
      for KirCII. The findings form a foundation for further understanding the
      specificity of trans-AT:ACP protein interactions and for engineering modular
      polyketide synthases to produce analogs. 

PMID- 24726833
TI  - Regulation of the ROS response dynamics and organization to PDGF motile stimuli
      revealed by single nanoparticle imaging.
AB  - Although reactive oxygen species (ROS) are better known for their harmful
      effects, more recently, H2O2, one of the ROS, was also found to act as a
      secondary messenger. However, details of spatiotemporal organization of specific
      signaling pathways that H2O2 is involved in are currently missing. Here, we use
      single nanoparticle imaging to measure the local H2O2 concentration and reveal
      regulation of the ROS response dynamics and organization to platelet-derived
      growth factor (PDGF) signaling. We demonstrate that H2O2 production is controlled
      by PDGFR kinase activity and EGFR transactivation, requires a persistent
      stimulation, and is regulated by membrane receptor diffusion. This temporal
      filtering is impaired in cancer cells, which may determine their pathological
      migration. H2O2 subcellular mapping reveals that an external PDGF gradient
      induces an amplification-free asymmetric H2O2 concentration profile. These
      results support a general model for the control of signal transduction based only
      on membrane receptor diffusion and second messenger degradation. 

PMID- 24726834
TI  - Hepatitis C virus present in the sera of infected patients interferes with the
      autophagic process of monocytes impairing their in-vitro differentiation into
      dendritic cells.
AB  - Autophagy has a pivotal role in the in-vitro monocyte differentiation into
      macrophages and dendritic cells (DCs), the most powerful antigen presenting cells
      (APC) with the unique capacity to initiate an adaptive immune response. Autophagy
      is also a mechanism by which these cells of innate immunity may degrade
      intracellular pathogens and mediate the antigen processing and presentation,
      essential to clear an infection. For these reasons, pathogens have learned how to
      manipulate autophagy for their own survival. In this study we found that
      hepatitis C virus (HCV), derived from sera of infected patients, blocked the
      autophagic process in differentiating monocytes, seen as LC3 II and p62
      expression levels. The suppression of autophagy correlated with a reduction of
      cathepsins D, B and proteolytic activity, and resulted in impairment of monocyte
      differentiation into DCs, as indicated by the reduction of CD1a acquirement.
      These data suggest that the block of autophagy might be one of the underlying
      mechanisms of the HCV-mediated immune subversion that frequently leads to viral
      persistence and chronic hepatitis. 

PMID- 24726835
TI  - Emotional regulatory function of receptor interacting protein 140 revealed in the
      ventromedial hypothalamus.
AB  - Receptor-interacting protein (RIP140) is a transcription co-regulator highly
      expressed in macrophages to regulate inflammatory and metabolic processes.
      However, its implication in neurological, cognitive and emotional conditions, and
      the cellular systems relevant to its biological activity within the central
      nervous system are currently less clear. A transgenic mouse line with macrophage
      specific knockdown of RIP140 was generated (MPhiRIPKD mice) and brain-region
      specific RIP140 knockdown efficiency evaluated. Mice were subjected to a battery
      of tests, designed to evaluate multiple behavioral domains at naive or following
      site-specific RIP140 re-expression. Gene expression analysis assessed TNF-alpha,
      IL-1beta, TGF-1beta, IL1-RA and neuropeptide Y (NPY) expression, and in vitro
      studies examined the effects of macrophage's RIP140 on astrocytes' NPY
      production. We found that RIP140 expression was dramatically reduced in
      macrophages within the ventromedial hypothalamus (VMH) and the cingulate cortex
      of MPhiRIPKD mice. These animals exhibited increased anxiety- and depressive-like
      behaviors. VMH-targeted RIP140 re-expression in MPhiRIPKD mice reversed its
      depressive- but not its anxiety-like phenotype. Analysis of specific
      neurochemical changes revealed reduced astrocytic-NPY expression within the
      hypothalamus of MPhiRIPKD mice, and in vitro analysis confirmed that conditioned
      medium of RIP140-silnenced macrophage culture could no longer stimulate NPY
      production from astrocytes. The current study revealed an emotional regulatory
      function of macrophage-derived RIP140 in the VMH, and secondary dysregulation of
      NPY within hypothalamic astrocyte population, which might be associated with the
      observed behavioral phenotype of MPhiRIPKD mice. This study highlights RIP140 as
      a novel target for the development of potential therapeutic and intervention
      strategies for emotional regulation disorders. 

PMID- 24726836
TI  - Programming of metabolic effects in C57BL/6JxFVB mice by exposure to bisphenol A
      during gestation and lactation.
AB  - The global rise in prevalence of obesity is not fully explained by genetics or
      life style factors. The developmental origins of health and disease paradigm
      suggests that environmental factors during early life could play a role. In this
      perspective, perinatal exposure to bisphenol A (BPA) has been indicated as a
      programming factor for obesity and related metabolic disorders later in life.
      Here we study early life programming by BPA using an experimental design that is
      relevant for human exposure. C57BL/6JxFVB hybrid mice were exposed during
      gestation and lactation via maternal feed to 8 non-toxic doses (0-3000 MUg/kg
      body weight/day (MUg/kg bw/d)) of BPA. After weaning, offspring were followed for
      20 weeks without further exposure. Adult male offspring showed dose-dependent
      increases of body and liver weights, no effects on fat pad weights and a dose
      dependent decrease in circulating glucagon. Female offspring showed a dose
      dependent decrease in body weight, liver, muscle and fat pad weights, adipocyte
      size, serum lipids, serum leptin and adiponectin. Physical activity was decreased
      in exposed males and suggested to be increased in exposed females. Brown adipose
      tissue showed slightly increased lipid accumulation in males and lipid depletion
      in females, and ucp1 expression was dose-dependently increased in females. The
      effects in females were more reliable and robust than in males due to wide
      confidence intervals and potential confounding by litter size for male data. The
      lowest derived BMDL (lower bound of the (two-sided) 90%-confidence interval for
      the benchmark dose) of 233 MUg/kg bw/d (for interscapular weight in females) was
      below the proposed BMDL of 3633 MUg/kg bw/d as a basis for tolerable daily
      intake. Although these results suggest that BPA can program for an altered
      metabolic phenotype, the sexual dimorphism of effects and diversity of outcomes
      among studies similar in design as the present study do not mark BPA as a
      specific obesogen. The consistency within the complex of observed metabolic
      effects suggests that upstream key element(s) in energy homeostasis are modified.
      Sex-dependent factors contribute to the final phenotypic outcome.

PMID- 24726837
TI  - Detection of sentinel lymph node in breast cancer recurrence may change adjuvant
      treatment decision in patients with breast cancer recurrence and previous
      axillary surgery.
AB  - Use of sentinel lymph node dissection in patients with ipsilateral breast cancer
      recurrence is still controversial. The objective of this study is to evaluate the
      feasibility of the sentinel lymph node in breast cancer recurrence (SLNBR) and
      whether the positivity had impact in the adjuvant treatment. Between 2008 and
      2012 we performed SLNBR in patients with ipsilateral breast tumor recurrence. We
      included 53 patients in a prospective study. Forty-three patients (81%) had a
      previous axillary lymph node dissection (ALND) and ten (19%) had a previous
      sentinel lymph node biopsy (SLNB). Identification rate after SLNB was 50% and
      after ALND was 60.5% (p = 0.4). Nine patients (26%) had a positive SLNBR.
      Adjuvant systemic treatment was given to all the patients with a positive SLNBR
      and to 23 (85%) with a negative SLNBR (p = 0.29). Six patients (66%) with
      positive SLNBR and 4 patients (14%) with negative SLNBR underwent radiation
      therapy (p < 0.01). As conclusions of our study we conclude that sentinel lymph
      node biopsy in breast tumor recurrence is feasible and significant differences
      were found in the use of radiation therapy in patients with a positive SLNBR.

PMID- 24726838
TI  - Microtubule dynamics regulates Akt signaling via dynactin p150.
AB  - Following activation at the plasma membrane, Akt is subsequently deactivated in
      the cytoplasm. Although activation and deactivation of Akt must sometimes be
      separated in order to elicit and control cellular responses, the exact details of
      the spatiotemporal organization of Akt signaling are incompletely understood.
      Here we show that microtubule dynamics specifically modulate the deactivation
      phase of Akt signaling. Localization of Akt to microtubules sustains its
      activity, while disruption of microtubules attenuates Akt signaling independent
      of its initial activation. Conversely, stabilization of microtubules elevates Akt
      signaling both in vitro and in muscle tissues in vivo. Localization of Akt to
      microtubules is mediated by the microtubule binding protein dynactin p150, which
      is shown to be a direct target of Akt. Finally, microtubule disruption-induced
      Akt deactivation contributes to delayed cell cycle progression and accelerated
      cell death. Taken together, we revealed that, after initiation, the overall
      intensity and duration of oncogenic Akt signaling are determined by microtubule
      dynamics, a mechanism that could be exploited for therapeutic purposes. 

PMID- 24726839
TI  - Downregulation of LAT1 expression suppresses cholangiocarcinoma cell invasion and
      migration.
AB  - Currently, there is no effective treatment for cholangiocarcinoma (CCA), which is
      the most prevalent in the northeastern part of Thailand. A new molecular target
      for the treatment of CCA is, therefore, urgently needed. Although L-type amino
      acid transporter 1 (LAT1) is highly expressed in CCA cells, its role in malignant
      phenotypes of CCA cells remains unclear. This study aimed to investigate the
      impact of LAT1 on proliferation, migration, and invasion of KKU-M213 cells, the
      CCA cells derived from Thai patients with intrahepatic cholangiocarcinoma.
      Results showed that KKU-M213 cells expressed all LAT isoforms (LAT1, LAT2, LAT3
      and LAT4). The expressions of LAT1 and its associated protein 4F2hc were highest
      whereas those of LAT2 and LAT4 were extremely low. Treatment with 2-aminobicyclo
      (2,2,1)-heptane-2-carboxylic acid (BCH) reduced L-leucine uptake concomitant with
      an inhibition of cell motility and, to a lesser extent, on cell proliferation. It
      also induced a time dependent up-regulation of LAT1 and 4F2hc expressions.
      Similarly, cell migration and invasion, but not proliferation, were reduced in
      LAT1 knockdown KKU-M213 cells. In addition, silencing of LAT1 inhibited the
      expressions of 4F2hc mRNA and protein whereas the expression of microRNA-7, the
      4F2hc down-regulator, was increased. Furthermore, the phosphorylation levels of
      ERK1/2 and p70S6K were reduced after LAT1 knockdown. Collectively, these results
      suggest that suppression of cell invasion and migration in LAT1 knockdown KKU
      M213 cells may be partly mediated through the inhibition of the 4F2hc-signaling
      pathway by the up-regulation of microRNA-7. Based on this finding, LAT1 may be a
      potential therapeutic target for treating CCA.

PMID- 24726840
TI  - Reduced phosphorylation of Stat3 at Ser-727 mediated by casein kinase 2 - protein
      phosphatase 2A enhances Stat3 Tyr-705 induced tumorigenic potential of glioma
      cells.
AB  - Signal transducer and activator of transcription 3 (Stat3) is a transcription
      factor that is involved in cell survival and proliferation and has been found to
      be persistently activated in most human cancers mainly through its
      phosphorylation at Tyr-705. However, the role and regulation of Stat3 Ser-727
      phosphorylation in cancer cells have not been clearly evaluated. In our findings,
      correlation studies on the expression of CK2 and Stat3 Ser-727 phosphorylation
      levels in human glioma patient samples as well as rat orthotopic tumor model show
      a degree of negative correlation. Moreover, brain tumor cell lines were treated
      with various pharmacological inhibitors to inactivate the CK2 pathway. Here,
      increased Stat3 Ser-727 phosphorylation upon CK2 inhibition was observed.
      Overexpression of CK2 (alpha, alpha' or beta subunits) by transient transfection
      resulted in decreased Stat3 Ser-727 phosphorylation. Stat3 Tyr-705 residue was
      conversely phosphorylated in similar situations. Interestingly, we found PP2A, a
      protein phosphatase, to be a mediator in the negative regulation of Stat3 Ser-727
      phosphorylation by CK2. In vitro assays prove that Ser-727 phosphorylation of
      Stat3 affects the transcriptional activity of its downstream targets like SOCS3,
      bcl-xl and Cyclin D1. Stable cell lines constitutively expressing Stat3 S727A
      mutant showed increased survival, proliferation and invasion which are
      characteristics of a cancer cell. Rat tumor models generated with the Stat3 S727A
      mutant cell line formed more aggressive tumors when compared to the Stat3 WT
      expressing stable cell line. Thus, in glioma, reduced Stat3 Ser-727
      phosphorylation enhances tumorigenicity which may be regulated in part by CK2
      PP2A pathway. 

PMID- 24726841
TI  - Competitor suppresses neuronal representation of food reward in the nucleus
      accumbens/medial striatum of domestic chicks.
AB  - To investigate the role of social contexts in controlling the neuronal
      representation of food reward, we recorded single neuron activity in the medial
      striatum/nucleus accumbens of domestic chicks and examined whether activities
      differed between two blocks with different contexts. Chicks were trained in an
      operant task to associate light-emitting diode color cues with three trial types
      that differed in the type of food reward: no reward (S-), a small reward/short
      delay option (SS), and a large reward/long-delay alternative (LL). Amount and
      duration of reward were set such that both of SS and LL were chosen roughly
      equally. Neurons showing distinct cue-period activity in rewarding trials (SS and
      LL) were identified during an isolation block, and activity patterns were
      compared with those recorded from the same neuron during a subsequent pseudo
      competition block in which another chick was allowed to forage in the same area,
      but was separated by a transparent window. In some neurons, cue-period activity
      was lower in the pseudo-competition block, and the difference was not ascribed to
      the number of repeated trials. Comparison at neuronal population level revealed
      statistically significant suppression in the pseudo-competition block in both SS
      and LL trials, suggesting that perceived competition generally suppressed the
      representation of cue-associated food reward. The delay- and reward-period
      activities, however, did not significantly different between blocks. These
      results demonstrate that visual perception of a competitive forager per se
      weakens the neuronal representation of predicted food reward. Possible functional
      links to impulse control are discussed. 

PMID- 24726842
TI  - VN/14-1 induces ER stress and autophagy in HP-LTLC human breast cancer cells and
      has excellent oral pharmacokinetic profile in female Sprague Dawley rats.
AB  - Resistance to aromatase inhibitors is a major concern in the treatment of breast
      cancer. Long-term letrozole cultured (LTLC) cells represent a model of resistance
      to aromatase inhibitors. The LTLC cells were earlier generated by culturing MCF
      7Ca, the MCF-7 human breast cancer cell line stably transfected with human
      placental aromatase gene for a prolonged period in the presence of letrozole. In
      the present study the effect of RAMBA, VN/14-1 on the sensitivity of LTLC cells
      upon multiple passaging and the mechanisms of action of VN/14-1 in such high
      passage LTLC (HP-LTLC) cells was investigated. We report that multiple passaging
      of LTLC cells (HP-LTLC cell clones) led to profound decrease in their sensitivity
      to VN/14-1. Additionally, microarray studies and protein analysis revealed that
      VN/14-1 induced marked endoplasmic reticulum (ER) stress and autophagy in HP-LTLC
      cells. We further report that VN/14-1 in combination with thapsigargin exhibited
      synergistic anti-cancer effect in HP-LTLC cells. Preliminary pharmacokinetics in
      rats revealed that VN/14-1 reached a peak plasma concentration (Cmax) within
      0.17h after oral dosing. Its absolute oral bioavailability was >100%. Overall
      these results indicate potential of VN/14-1 for further clinical development as a
      potential oral agent for the treatment of breast cancer. 

PMID- 24726843
TI  - Promising anti-diabetes mellitus activity in rats of beta-amyrin palmitate
      isolated from Hemidesmus indicus roots.
AB  - While evaluating the toxicity of the tuberous root extracts of Hemidesmus
      indicus, a traditional medicinal plant, the glucose lowering property of the root
      was observed by the investigators. Therefore, it was thought of interest to
      isolate the anti-hyperglycemic principle from the root and determine its utility
      to develop an anti-diabetes mellitus medicine. The active principle was isolated
      from H. indicus root extract by anti-hyperglycemic activity guided
      chromatographic techniques. Glucose tolerance test in rats was used to evaluate
      the anti-hyperglycenic property. Anti-diabetes mellitus property was evaluated in
      alloxan-induced diabetic rats as well as streptozotocin-induced (type-2 model)
      diabetic rats. The active principle was isolated and identified with spectral
      data as beta-amyrin palmitate. Although it is a known compound, its presence in
      H. indicus is not known previously. It was observed for the first time that beta
      amyrin palmitate has remarkable anti-hyperglycemic activity in orally glucose
      loaded rats. Further, interestingly, it exhibited excellent anti-diabetes
      mellitus activity in both alloxan-diabetic and streptozotocin-diabetic rats at a
      very low concentration (50ug/kg body weight). One of the mechanisms of action of
      beta-amyrin palmitate appears to be blocking the entry of glucose from the
      intestine. beta-Amyrin palmitate is very promising to develop a medicine for
      diabetes for combination therapy and/or mono-therapy. 

PMID- 24726844
TI  - Opioid/NMDA receptors blockade reverses the depressant-like behavior of foot
      shock stress in the mouse forced swimming test.
AB  - Opioid and glutamatergic receptors have a key role in depression following
      stress. In this study, we assessed opioid and glutamatergic receptors interaction
      with the depressant-like behavior of acute foot-shock stress in the mouse forced
      swimming test. Stress was induced by intermittent foot shock stimulation during
      30min and swim periods were afterwards conducted by placing mice in separated
      glass cylinders filled with water for 6min. The immobility time during the last
      4min of the test was considered. Acute foot-shock stress significantly increased
      the immobility time of mice compared to non-stressed control group (P<=0.01).
      Administration of non-selective opioid receptors antagonist, naltrexone (1 and
      2mg/kg, i.p.), and the selective non-competitive NMDA receptor antagonist, MK-801
      (0.05mg/kg, i.p.), and the selective serotonin reuptake inhibitor, fluoxetine
      (5mg/kg), significantly reduced the immobility time in stressed animals
      (P<=0.01). Lower doses of MK-801 (0.01mg/kg), naltrexone (0.3mg/kg), NMDA
      (75mg/kg) and morphine(5mg/kg) had no effect on foot-shock stressed mice.
      Combined treatment of sub-effective doses of naltrexone and MK-801 significantly
      showed an antidepressant-like effect (P<=0.001). On the other hand, co
      administration of non-effective doses of NMDA and morphine with effective doses
      of naltrexone and MK-801 reversed the anti-immobility effect of these drugs.
      Taken together, we have for the first time demonstrated the possible role of
      opioid/NMDA receptors signaling in the depressant-like effect of foot-shock
      stress, and proposed the use of drugs that act like standard anti-depressants in
      stress-induced depression. 

PMID- 24726845
TI  - 13F-1, a novel 5-fluorouracil prodrug containing an Asn-Gly-Arg (NO2) COOCH3
      tripeptide, inhibits human colonic carcinoma growth by targeting Aminopeptidase N
      (APN/CD13).
AB  - 13F-1 is a 5-fluorouracil prodrug containing an Asn-Gly-Arg (NO2) COOCH3
      tripeptide. 13F-1 might possess the activity against cancer growth by targeting
      Aminopeptidase N (APN/CD13). Our goal in this study was to evaluate the
      inhibitory effect of 13F-1 on the growth of human colonic carcinoma by both in
      vitro and in vivo studies. Experiments were performed in colonic carcinoma
      Colo205 cells, which highly express APN/CD13 on cell surface. The inhibition of
      13F-1 on cancer cell growth was estimated by the colorimetric and clonogenic
      assays. The assays of Annexin V-FITC/PI and JC-1 fluorescence probe were employed
      to determine the apoptotic cells. Further experiment was performed in mice
      bearing Colo205 xenografts. 13F-1 was injected for three consecutive weeks. The
      specimens of Colo205 xenografts were removed for TUNEL staining and western
      blotting analysis. The expressions of APN/CD13 were analyzed by immunofluorescent
      flow cytometry and western blotting assays. 13F-1 significantly inhibited Colo205
      cell proliferation. 13F-1 by injection delayed the expansion of Colo205
      xenografts without significant toxicity to mice. The inhibitory effect of 13F-1
      might arise from its role in apoptotic induction. Further analysis indicated that
      13F-1 strongly inhibited APN/CD13 expression on cancer cell surface. In contrast,
      5-FU did not affect APN/CD13 expression. These results indicated the mechanism of
      13F-1 action that 13F-1's effect was associated with its role in suppression of
      APN/CD13 expression. Conclusion, 13F-1 could be developed as a promising agent
      for treatment of cancers with high expression of APN/CD13. 

PMID- 24726846
TI  - K+ channels as potential targets for the treatment of gastrointestinal motor
      disorders.
AB  - K(+) channels play important functional roles in excitable cells, as neurons and
      muscle cells. The activation or inhibition of K(+) channels hyperpolarizes or
      depolarizes the cell membrane, respectively. These effects determine in the
      smooth muscle decrease or increase in Ca(2+) influx through voltage-gated Ca(2+)
      (CaV1.2) channels and relaxation or contraction, respectively. Recent studies
      highlight the importance of voltage-dependent type 7 K(+) (KV7 or KCNQ) channels
      in regulating muscle tone and contractility in stomach and colon. KV7 channels,
      that include 5 subtypes (KV7.1-7.5), are activated at relatively negative
      potential values, close to those of the resting membrane potential for the smooth
      muscle cells of some segments of the gastrointestinal tract. Thus, they
      contribute to set the resting membrane potential and their blockade induces
      increase in smooth muscle contractility in stomach and colon. In addition, KV7
      channel activation produces profound relaxations of gastric and colonic smooth
      muscle. Therefore, KV7 channel activators could be used to relax the smooth
      muscle and relieve symptoms in diseases such as functional dyspepsia and
      irritable bowel syndrome with prevalent diarrhea. The discovery of activators
      selective for the channel subtypes present in the smooth muscle, mainly KV7.4 and
      7.5, would allow avoiding adverse cardiac and nervous system effects. A further
      step forward would be characterizing putative differences among the KV7 channel
      subtypes expressed in the various smooth muscles and synthesizing molecules
      specific for the gastrointestinal smooth muscle. 

PMID- 24726847
TI  - Dimebon, an antihistamine drug, inhibits glutamate release in rat cerebrocortical
      nerve terminals.
AB  - The excessive release of glutamate is a critical element in the neuropathology of
      acute and chronic brain disorders. The purpose of the present study was to
      investigate the effect and possible mechanism of dimebon, an antihistamine with a
      neuroprotective profile, on endogenous glutamate release in the nerve terminals
      (synaptosomes) of the rat cerebral cortex. Dimebon inhibited the release of
      glutamate that was evoked by exposing the synaptosomes to the K(+) channel
      blocker 4-aminopyridine, and this effect was prevented by chelating extracellular
      Ca(2+) ions, and the vesicular transporter inhibitor bafilomycin A1. Dimebon
      inhibited depolarization-evoked increase in cytosolic free Ca(2+) concentration,
      and the dimebon-mediated inhibition of glutamate release was prevented by the
      Cav2.2 (N-type) and Cav2.1 (P/Q-type) channel blocker omega-conotoxin MVIIC. The
      inhibitory action of dimebon on glutamate release was not due to its decreasing
      synaptosomal excitability, because dimebon did not alter the resting synaptosomal
      membrane potential or 4-aminopyridine-mediated depolarization. Furthemore, the
      dimebon effect on 4-aminopyridine-evoked glutamate release was prevented by the
      protein kinase C inhibitor, and dimebon substantially reduced the 4-AP-induced
      phosphorylation of protein kinase C. However, the dimebon-mediated inhibition of
      glutamate release was unaffected by the N-methyl-d-aspartate receptor agonist or
      antagonist. These results suggest that dimebon inhibits glutamate release from
      rat cortical synaptosomes by suppressing presynaptic voltage-dependent Ca(2+)
      entry and protein kinase C activity. This implies that the inhibition of
      glutamate release is an additional pharmacological activity of dimebon that may
      play a critical role in the apparent clinical efficacy of this compound. 

PMID- 24726848
TI  - Face-to-face comparison of the predictive validity of two models of neuropathic
      pain in the rat: analgesic activity of pregabalin, tramadol and duloxetine.
AB  - We compared the preclinical analgesic activity of three marketed drugs with
      different pharmacological properties, pregabalin, tramadol and duloxetine,
      described as effective against neuropathic pain in the clinic. These drugs were
      tested against evoked pain in two different neuropathic models in the rat, the
      Bennett (CCI) and the Chung (SNL) models. The selected endpoints were tactile
      allodynia, tactile hyperalgesia, heat hyperalgesia and cold allodynia. Although
      all three drugs displayed analgesic activity, the effects observed varied
      according to the behavioral evaluation. Pregabalin showed clear analgesic effects
      against cold allodynia and tactile hyperalgesia in both the CCI and Chung models.
      Tramadol was active against all four endpoints in the Chung model with similar
      effects in the CCI model, apart from tactile allodynia. Duloxetine inhibited
      tactile allodynia and heat hyperalgesia in both neuropathic pain models. It also
      displayed efficacy against tactile hyperalgesia in the CCI model and against cold
      allodynia in the Chung model. These data confirm that the CCI and the Chung
      models of neuropathic pain do not detect the activity of analgesics with the same
      sensitivity. Furthermore, the mode of stimulation (tactile or thermal) and the
      type of endpoint (allodynia or hyperalgesia) can further influence the observed
      efficacy of gold standards as well as novel compounds developed for treating
      neuropathic pain symptoms. 

PMID- 24726850
TI  - The effects of nitroglycerin during cardiopulmonary resuscitation.
AB  - The outcome for both in-hospital and out-of hospital cardiac arrest remains
      dismal. Vasopressors are used to increase coronary perfusion pressure and thus
      facilitate return of spontaneous circulation during cardiopulmonary
      resuscitation. However, they are associated with a number of potential adverse
      effects and may decrease endocardial and cerebral organ blood flow. Nitroglycerin
      has a favourable haemodynamic profile which promotes forward blood flow. Several
      studies suggest that combined use of nitroglycerin with vasopressors during
      resuscitation, is associated with increased rates of resuscitation and improved
      post-resuscitation outcome. This article reviews the effects of nitroglycerin
      during cardiopulmonary resuscitation and postresuscitation period, as well as the
      beneficial outcomes of a combination regimen consisting of a vasopressor and a
      vasodilator, such as nitroglycerin. 

PMID- 24726849
TI  - Farrerol regulates occludin expression in hydrogen peroxide-induced EA.hy926
      cells by modulating ERK1/2 activity.
AB  - Endothelial tight junction is a crucial intracellular junctional structure that
      controls paracellular permeability across vascular endothelium. Oxidative stress
      mediated elevation in endothelial permeability is associated with pathogenesis of
      several cardiovascular diseases. In the present research, the regulation of
      farrerol on occludin, a transmembrane proteins associated with endothelial tight
      junction, was investigated in hydrogen peroxide-induced human endothelium-derived
      EA.hy926 cells. Western blot analysis demonstrated that H2O2 exposure caused a
      significant decrease in occludin expression, but had little effect on ZO-1
      expression, and the decrease of occludin expression was significantly attenuated
      by farrerol in a dose-dependent manner. Meanwhile, immunofluorescent staining
      assay also demonstrated that the loss of occludin expression induced by H2O2
      exposure was restored by farrerol pretreatment. Further investigations showed
      that farrerol prevented H2O2-induced activation of extracellular signal-regulated
      kinase (ERK) 1/2 in a dose-dependent manner. The use of U0126, a specific
      inhibitor of MEK1/2, proved that H2O2-induced decrease of occludin in EA.hy926
      cells was likely associated with activation of ERK1/2, which indicated that the
      regulation of farrerol on occludin expression in H2O2-induced EA.hy926 cells was
      likely related to the modulation of ERK1/2 activation. In conclusion, the present
      study demonstrates for the first time that farrerol has potential effects on
      oxidative stress-induced endothelial tight junction disruption and suggests that
      farrerol is a potential candidate for the intervention of endothelial
      permeability-associated cardiovascular diseases. 

PMID- 24726851
TI  - Aorta pathology and pregnancy.
AB  - In addition to the haemodynamic changes in pregnancy, hormones also induce
      changes in the aortic wall. Women with diseases like Marfan syndrome, Ehlers
      Danlo syndrome, or other aortic abnormalities, have an increased risk of
      complications during pregnancy. Counselling and risk assessment before pregnancy
      is mandatory for all women with known aortic disease. Proper information should
      be provided about the risks of morbidity and mortality during pregnancy and
      information on the risks for the fetus, including the potential recurrence of
      disease in the offspring. Evaluation of past medical and family history, the
      aortic size before conception, and any increase in size before and during
      pregnancy, is essential to try and estimate the risk of aortic dissection. If the
      aorta is dilated, prophylactic repair before pregnancy may be indicated. In some
      cases, elective surgery during pregnancy may be warranted. In women with a
      severely dilated ascending aorta, caesarean section is, at present, the advised
      mode of delivery. 

PMID- 24726852
TI  - Risk stratification and hierarchy of antenatal care.
AB  - Cardiac disease is the leading cause of maternal death in the UK. The triennial
      maternal mortality reports have repeatedly highlighted failure to recognise the
      level of risk as a major contributing factor to the deaths of these women. Once
      the level of risk has been recognised, services then need to be organised in a
      way that supports the needs of the highest risk women, but avoids unnecessary
      intervention for women at lower risk. Risk scoring systems and lesion-specific
      indicators may help predict maternal and neonatal outcomes. Care can then be
      planned accordingly, to optimise the outcome for the woman and her baby. 

PMID- 24726853
TI  - Predicting patient acuity from electronic patient records.
AB  - BACKGROUND: The ability to predict acuity (patients' care needs), would provide a
      powerful tool for health care managers to allocate resources. Such estimations
      and predictions for the care process can be produced from the vast amounts of
      healthcare data using information technology and computational intelligence
      techniques. Tactical decision-making and resource allocation may also be
      supported with different mathematical optimization models. METHODS: This study
      was conducted with a data set comprising electronic nursing narratives and the
      associated Oulu Patient Classification (OPCq) acuity. A mathematical model for
      the automated assignment of patient acuity scores was utilized and evaluated with
      the pre-processed data from 23,528 electronic patient records. The methods to
      predict patient's acuity were based on linguistic pre-processing, vector-space
      text modeling, and regularized least-squares regression. RESULTS: The
      experimental results show that it is possible to obtain accurate predictions
      about patient acuity scores for the coming day based on the assigned scores and
      nursing notes from the previous day. Making same-day predictions leads to even
      better results, as access to the nursing notes for the same day boosts the
      predictive performance. Furthermore, textual nursing notes allow for more
      accurate predictions than previous acuity scores. The best results are achieved
      by combining both of these information sources. The developed model achieves a
      concordance index of 0.821 when predicting the patient acuity scores for the
      following day, given the scores and text recorded on the previous day.
      CONCLUSIONS: By applying language technology to electronic patient documents it
      is possible to accurately predict the value of the acuity scores of the coming
      day based on the previous days assigned scores and nursing notes.

PMID- 24726854
TI  - Dysanapsis ratio as a predictor for expiratory flow limitation.
AB  - To determine the efficacy of the dysanapsis ratio (DR) in predicting expiratory
      flow limitation during exercise, 146 subjects (73 men, 73 women) performed
      standard pulmonary function and maximal incremental exercise tests. Tidal flow
      volume loops were recorded at maximal exercise with maximal flow-volume loops
      measured pre- and post-exercise. Men had larger (p<0.05) lung volumes, flow
      rates, and VO2max compared to women, but DR was similar (0.21+/-0.05 vs. 0.20+/
      0.06, respectively, p>0.05). VO2max was not different (p>0.05) between the EFL
      subjects compared to the non-EFL subjects for both men and women. Men with EFL
      compared to non-EFL men had smaller FVC (5.16+/-0.89L vs. 5.67+/-0.86L, p<0.05)
      and DR (0.19+/-0.05 vs. 0.23+/-0.04, p<0.05). Similarly, women with EFL compared
      to non-EFL had significantly smaller DR (0.18+/-0.05 vs. 0.24+/-0.05), but
      similar FVC (3.88+/-0.52 vs. 4.12+/-0.64, p>0.05). A DR threshold was not
      determined; however, a DR continuum exists with increasing DR leading to
      decreased prevalence of EFL. In conclusion, DR is effective in determining the
      likelihood of EFL at maximal exercise. 

PMID- 24726855
TI  - Reply from authors re: Bertrand Tombal. Zometa European Study (ZEUS): another
      failed crusade for the holy grail of prostate cancer bone metastases prevention?
      Eur Urol 2015;67:492-4: ZEUS: the quest for the holy grail of prostate cancer
      bone metastases prevention continues.

PMID- 24726856
TI  - A prospective and comparative study between stapled hemorrhoidopexy and
      hemorrhoidal artery ligation with mucopexy.
AB  - AIM: The aim of this study was to compare the efficacy between stapled
      hemorrhoidopexy (Longo technique) and transanal hemorrhoidal artery ligation with
      mucopexy (THDm) in the treatment of hemorrhoidal disease. PATIENTS AND METHODS:
      From June 2009 to January 2011, 81 patients having grade II or III hemorrhoidal
      disease underwent prospective evaluation followed by surgery at two centers (27
      Longo and 54 THDm). Symptoms (bleeding, tenesmus, prolapse, fecal incontinence,
      pain) and the satisfaction score were compared on the first post-operative day
      and at 1, 6, 12, and 24 months thereafter. The follow-up was 24 months. RESULTS:
      There was no difference in mean length of stay. One complication (recto-vaginal
      fistula) was observed after Longo. The prolapse score was significantly lower
      after THDm than after Longo on the first post-operative day (P < 0.0015).
      Bleeding score after THDm was significantly lower on the first post-operative day
      (P = 0.04), but higher thereafter (P = 0.03 and P = 0.04). Tenesmus score after
      THDm was significantly lower for the first three months (P < 0.06 and 0.001). On
      the first post-operative day and at one month, the visual analog pain score was
      significantly lower after THDm than that after Longo (P < 0.0003 et P < 0.01). On
      the first post-operative day and at one month, the satisfaction score was higher
      after THDm than after Longo (P < 0.001). CONCLUSION: THDm was safe and effective.
      Short-term outcomes after THDm were better than after Longo but long-term results
      seemed to be similar.

PMID- 24726857
TI  - The essential role of infection-detection technologies for malaria elimination
      and eradication.
AB  - Recent emphasis on malaria elimination and eradication (E&E) goals is changing
      the way that experts evaluate malaria diagnostic tools and tactics. As prevalence
      declines, the focus of malaria management is pivoting toward low-density,
      subclinical infections and geographically and demographically concentrated
      reservoirs. These and other changes present challenges and opportunities for
      innovations in malaria diagnostics aimed at meeting the needs of malaria
      elimination programs. Developing such technologies requires a review of the
      operational approaches to detecting malaria infections in areas of declining
      prevalence. Here we review recent research on epidemiology and biology related to
      malaria elimination and operational factors that influence E&E strategies. We
      further propose use-scenarios and a target product profile framework to define
      and prioritize the required attributes of infection-detection technologies. 

PMID- 24726858
TI  - The role of bovine gammadelta T cells and their WC1 co-receptor in response to
      bacterial pathogens and promoting vaccine efficacy: a model for cattle and
      humans.
AB  - gammadelta T cells are critical to immune surveillance and protection since they
      are found as resident cells in many organs and tissues, including in humans and
      ruminants, and circulate at substantial numbers in the blood. It is known that
      gammadelta T cells contribute to cellular immunity and protection against
      important pathogens including organizing granulomas in response to Mycobacteria.
      We have shown that IFNgamma-producing bovine gammadelta T cells bearing the WC1
      co-receptor are the major cell population responding in recall responses to
      Leptospira during the first month following priming by vaccination against
      serovar Hardjo. To date, successful vaccines largely include those to diseases
      that only require antibody responses for protection and attempts at creating
      subunit peptide vaccines to stimulate conventional alphabeta T cells for cellular
      immune responses have been mostly unsuccessful. However, activation of
      nonconventional T cells, such as gammadelta T cells that direct adaptive T cell
      responses, has received little attention for improving vaccines because it is not
      clear how best to prime gammadelta T cells for recall responses. Annotation of
      the bovine genome showed there were 13 WC1 molecules coded for by individual
      genes. This gene number is conserved among breeds and individuals and expression
      of the WC1 molecules are distributed among cells to form a number of gammadelta T
      cell subsets. Using RNA silencing, we have shown that the WC1 co-receptor
      contributes to the ability of gammadelta T cells to respond to Leptospira spp.
      The Leptospira-responsive gammadelta T cells are found within a subset of the
      serologically defined WC1.1(+) gammadelta T cell subpopulation and our data
      indicate that the WC1 molecules expressed act as pattern recognition receptors
      interacting directly with bacterial components. We are now extending this work to
      Mycobacteria bovis. 

PMID- 24726859
TI  - Cytokines transcript levels in lung and lymphoid organs during genotype 1 Porcine
      Reproductive and Respiratory Syndrome Virus (PRRSV) infection.
AB  - Porcine Reproductive and Respiratory Syndrome (PRRS) is one of the most
      economically important diseases of swine. PRRS virus (PRRSV) infection in the pig
      is characterized by a weak or absent host innate immune response. The underlying
      mechanisms of PRRSV pathogenesis are still unclear. The analysis of transcript
      levels represents an alternative to immunoassays for the detection of cytokines
      that sometimes are difficult to detect due to their low amounts. This study sets
      out to determine the differences in pathogenesis and the immune response between
      lung, tonsil, tracheobronchial lymph node (Tb-LN) and retropharyngeal LN (Rf-LN)
      of PRRSV 2982 strain infected pigs. PRRSV strain 2982 avoided the onset of an
      effective innate immune response, especially in PRRSV main target (lung) and
      reservoir (tonsil) organs. PRRSV lead to an impaired expression of IFN-alpha and
      TNF-alpha gene expression, which finally induced a weak and delayed adaptive
      immune response through an inefficient IL-12 and IFN-gamma expression. Finally,
      PRRSV replication favored the expression of the anti-inflammatory IL-10 cytokine
      in infected pigs. 

PMID- 24726860
TI  - Day 3 Poly (I:C)-activated dendritic cells generated in CellGro for use in cancer
      immunotherapy trials are fully comparable to standard Day 5 DCs.
AB  - BACKGROUND: Dendritic cells (DCs) are professional antigen-presenting cells that
      are capable of inducing immune responses. DC-based vaccines are normally
      generated using a standard 5- to 7-day protocol. To shorten the DC-based vaccine
      production for use in cancer immunotherapy, we have developed a fast DC protocol
      by comparing standard DCs (Day 5 DCs) and fast DCs (Day 3 DCs). METHODS: We
      tested the generation of Day 5 versus Day 3 DCs using CellGro media and
      subsequent activation by two activation stimuli: Poly (I:C) and LPS. We evaluated
      DC morphology, viability, phagocyte activity, cytokine production and ability to
      stimulate antigen-specific T cells. RESULTS: Day 5 and Day 3 DCs exhibited
      similar phagocytic capacity. Poly (I:C)-activated Day 5 DCs expressed higher
      levels of the costimulatory and surface molecules CD80, CD86 and HLA-DR compared
      to Poly (I:C)-activated Day 3 DCs. Nevertheless, LPS-activated Day 5 and Day 3
      DCs were phenotypically similar. Cytokine production was generally stronger when
      LPS was used as the maturation stimulus, and there were no significant
      differences between Day 5 and Day 3 DCs. Importantly, Day 5 and Day 3 DCs were
      able to generate comparable numbers of antigen-specific CD8(+) T cells. The
      number of Tregs induced by Day 5 and Day 3 DCs was also comparable. CONCLUSION:
      We identified monocyte-derived DCs generated in CellGro for 3 days and activated
      using Poly (I:C) similarly potent in most functional aspects as DCs produced by
      the standard 5 day protocol. These results provide the rationale for the
      evaluation of faster protocols for DC generation in clinical trials.

PMID- 24726862
TI  - Oxidative stress induces claudin-2 nitration in experimental type 1 diabetic
      nephropathy.
AB  - Renal complications in diabetes are severe and may lead to renal insufficiency.
      Early alterations in tight junction (TJ) proteins in diabetic nephropathy (DN)
      have not been explored and the role of oxidative stress in their disassembly has
      been poorly characterized. We investigated the expression and distribution of TJ
      proteins: claudin-5 in glomeruli (GL), occludin and claudin-2 in proximal tubules
      (PTs), and ZO-1 and claudin-1, -4, and -8 in distal tubules (DTs) of rats 21 days
      after streptozotocin injection. Redox status along the nephron segments was
      evaluated. Diabetes increased kidney injury molecule-1 expression. Expression of
      sodium glucose cotransporters (SGLT1 and SGLT2) and facilitative glucose
      transporter (GLUT2) was induced. Increased oxidative stress was present in GL and
      PTs and to a lesser extent in DTs (measured by superoxide production and PKCbeta2
      expression), owing to NADPH oxidase activation and uncoupling of the endothelial
      nitric oxide synthase-dependent pathway. Claudin-5, occludin, and claudin-2
      expression was decreased, whereas claudin-4 and -8 expression increased. ZO-1 was
      redistributed from membrane to cytosol. Increased nitration of tyrosine residues
      in claudin-2 was found, which might contribute to decrement of this protein in
      proximal tubule. In contrast, occludin was not nitrated. We suggest that loss of
      claudin-2 is associated with increased natriuresis and that loss of glomerular
      claudin-5 might explain early presence of proteinuria. These findings suggest
      that oxidative stress is related to alterations in TJ proteins in the kidney that
      are relevant to the pathogenesis and progression of DN and for altered sodium
      regulation in diabetes. 

PMID- 24726861
TI  - Peroxiredoxin VI oxidation in cerebrospinal fluid correlates with traumatic brain
      injury outcome.
AB  - Traumatic brain injury (TBI) patients would benefit from the identification of
      reliable biomarkers to predict outcomes and treatment strategies. In our study,
      cerebrospinal fluid (CSF) from patients with severe TBI was evaluated for oxidant
      stress-mediated damage progression after hospital admission and subsequent
      ventriculostomy placement. Interestingly, substantial levels of peroxiredoxin VI
      (Prdx6), a major antioxidant enzyme normally found in astrocytes, were detected
      in CSF from control and TBI patients and were not associated with blood
      contamination. Functionally, Prdx6 and its associated binding partner glutathione
      S-transferase Pi (GSTP1-1, also detected in CSF) act in tandem to detoxify lipid
      peroxidation damage to membranes. We found Prdx6 was fully active in CSF of
      control patients but becomes significantly inactivated (oxidized) in TBI.
      Furthermore, significant and progressive oxidation of "buried" protein thiols in
      CSF of TBI patients (compared to those of nontrauma controls) was detected over a
      24-h period after hospital admission, with increased oxidation correlating with
      severity of trauma. Conversely, recovery of Prdx6 activity after 24h indicated
      more favorable patient outcome. Not only is this the first report of an
      extracellular form of Prdx6 but also the first report of its detection at a
      substantial level in CSF. Taken together, our data suggest a meaningful
      correlation between TBI-initiated oxidation of Prdx6, its specific phospholipid
      hydroperoxide peroxidase activity, and severity of trauma outcome. Consequently,
      we propose that Prdx6 redox status detection has the potential to be a biomarker
      for TBI outcome and a future indicator of therapeutic efficacy. 

PMID- 24726863
TI  - Interaction of plasma glutathione redox and folate deficiency on arsenic
      methylation capacity in Bangladeshi adults.
AB  - Inorganic arsenic(As) is metabolized through a series of methylation reactions
      catalyzed by arsenic(III)-methyltransferase (AS3MT), resulting in the generation
      of monomethylarsonic (MMAs) and dimethylarsinic acids (DMAs). AS3MT activity
      requires the presence of the methyl donor S-adenosylmethionine, a product of
      folate-dependent one-carbon metabolism, and a reductant. Although glutathione
      (GSH), the primary endogenous antioxidant, is not required for As methylation,
      GSH stimulates As methylation rates in vitro. However, the relationship between
      GSH redox and As methylation capacity in humans is unknown. We wished to test the
      hypothesis that a more oxidized plasma GSH redox status is associated with
      decreased As methylation capacity and examine whether these associations are
      modified by folate nutritional status. Concentrations of plasma GSH and GSSG,
      plasma folate, total blood As (bAs), total urinary As (uAs), and uAs metabolites
      were assessed in a cross-sectional study of n=376 Bangladeshi adults who were
      chronically exposed to As in drinking water. We observed that a decreased plasma
      GSH/GSSG ratio (reflecting a more oxidized redox state) was significantly
      associated with increased urinary %MMA, decreased urinary %DMA, and increased
      total bAs in folate-deficient individuals (plasma folate <= 9.0 nmol/L).
      Concentrations of plasma GSH and GSSG were independently associated with
      increased and decreased As methylation capacity, respectively. No significant
      associations were observed in folate-sufficient individuals, and interactions by
      folate status were statistically significant. Our findings suggest that GSH/GSSG
      redox regulation might contribute to the large interindividual variation in As
      methylation capacity observed in human populations.

PMID- 24726865
TI  - Epitope distribution in ordered and disordered protein regions. Part B - Ordered
      regions and disordered binding sites are targets of T- and B-cell immunity.
AB  - Intrinsically disordered proteins exist in highly flexible conformational states
      linked to different protein functions. In this work, we have presented evidence
      that HLA class-I- and class-II-binding T-cell epitopes, experimentally verified
      in several tumor-associated antigens and nuclear systemic autoantigens, are
      predominantly located in ordered protein regions or at disorder/order
      borderlines, defined by the majority of analyzed publicly available disorder
      predictors. We have also observed the overlapping of secondary structural
      elements and prevalently hydrophobic regions with T-cell epitopes in Epstein Barr
      Virus (EBV) nuclear antigen 1 (EBNA-1), cancer/testis antigen MAGE-A4, and Sm
      B/B', U1 snRNPA (U1A) and U1-70kDa autoantigens. The results are in accordance
      with the clustering of the predicted HLA class-I and class-II epitopes in protein
      parts which encompass the consensus of ordered regions, determined by individual
      disorder predictors. Some HLA class-II epitopes and linear B-cell epitopes were
      located near the segments predicted to have elevated crystallographic B factor in
      EBNA-1, Sm-B/B' and U1 snRNP A proteins, suggesting that protein flexibility
      could influence the structural availability of epitopes. Naturally processed T
      cell epitopes and linear B-cell epitopes could also be found within putative
      disordered binding sites, determined by "dips" in the prevalently disordered
      parts of prediction profiles of the majority of disorder predictors, and peaks in
      ANCHOR-prediction profile. Two minor antigenic regions within EBNA-1, mapped to
      the residues 58-85 and 398-458, encompassing putative disordered binding sites,
      contain epitopes connected with anti-Ro 60kDa and anti-Sm B/B' autoimmunity in
      systemic lupus erythematosus. One of these regions overlaps residues 395-450,
      identified as the binding site of USP7 (HAUSP), which regulates the EBNA-1
      replication function. In Sm-B/B', one of the putative disordered binding sites
      (residues 114-165) encompasses the T-cell epitope 136-153, while another,
      residues 200-216, flanks two proline-rich B-cell epitopes (residues 190-198 and
      216-222), overlapping the preferred CD2BP2-GYF-binding motif (R/K/G)XXPPGX(R/K),
      characteristic of splicosomal proteins. We have noticed that the same motif
      (residues 397-403) is mimicked in EBNA-1 and overlaps epitope 398-404, involved
      in anti-Sm B/B' autoimmunity. The majority of recognized T- and B-cell epitopes
      in analyzed autoantigens or tumor-associated antigens appertain to the ordered or
      transient protein structures. The congruence between certain B- and T-cell
      epitopes and predicted disordered binding sites or protein-binding eukaryotic
      motifs in the antigens participating in molecular complexes might influence the
      capture of antigens, their processing and subsequent presentation and
      immunodominance. 

PMID- 24726866
TI  - Skeletal-related events and mortality among older men with advanced prostate
      cancer.
AB  - OBJECTIVE: Skeletal-related events (SREs) are defined as a cluster of events
      including clinical diagnoses and treatment. Using claims data, the burden of SREs
      as a group has been reported among patients with cancer. We investigate the
      mortality impact of subcomponents of SREs, a topic that has received limited
      attention among older men. MATERIALS AND METHODS: We analyzed prostate cancer
      (PCa) and all-cause mortality among men diagnosed with metastatic PCa from 2000
      to 2007 using Surveillance, Epidemiology, and End Results data linked with 1999
      2009 Medicare data. We created three measures of pathological fracture (PF),
      spinal cord compression (SCC), and bone surgery (BS) that differed in the use of
      claims-based bone metastasis information. We reported covariate-adjusted hazard
      ratios (HRs) using the full sample and a propensity score-matched sample (PSMS).
      RESULTS: Application of inclusion/exclusion criteria resulted in 7062 men in the
      full sample (1776 in the PSMS). PCa-specific (all-cause mortality) was 54% (80%)
      at a median follow-up of 609days. SRE prevalence ranged from 9.7% to 17.1% across
      the measures. In a PCa mortality model, the HR associated with an SRE ranged from
      1.07 (0.98-1.16) to 1.31 (1.18-1.45). The HRs for SCC and PF were statistically
      significant and positively associated with PCa-specific mortality. The results
      for BS depended on the measure. Results for SCC and BS, but not for PF, were
      preserved using a PSMS. CONCLUSIONS: The relationship between SREs and mortality
      among older men with metastatic PCa was driven by SCC and depended on the
      definition used to measure SREs.

PMID- 24726867
TI  - Do age and quality of life of patients with cancer influence quality of life of
      the caregiver?
AB  - OBJECTIVE: There are significant burdens associated with providing care for loved
      ones with cancer. However, caregiver quality of life (QOL) is often overlooked.
      With the increasing number of older adults with cancer, it is important to
      determine whether a patient's age and QOL have any association with the
      caregiver's QOL. The objective of our study was to describe caregiver QOL and
      explore whether patient age and other psychosocial factors impact caregiver QOL.
      MATERIALS AND METHODS: Baseline information from patients with advanced cancer
      undergoing radiation and their caregivers, who were enrolled in a randomized,
      controlled clinical trial to test the effectiveness of a structured,
      multidisciplinary QOL intervention, was analyzed for this study. Caregivers
      completed the Caregiver Quality of Life Index-Cancer (CQOLC) Scale. Both patients
      and caregivers completed the Linear Analogue Self-Assessment (LASA) to measure
      QOL, and Profile of Mood States (POMS) to measure mood states. RESULTS: Overall,
      131 patient-caregiver pairs participated in the study. At baseline, caregivers of
      older adults (>=65years) had higher mental (P=0.01), emotional (P=0.003),
      spiritual (P<0.01), and social support (P=0.03) LASA QOL scores. Caregivers of
      older adults also had higher baseline QOL (CQOLC, P=0.003) and mood (POMS,
      P=0.04) than caregivers of younger adults. Caregivers of patients with higher
      LASA QOL scores had higher overall (P=0.02), mental (P=0.006), physical (P=0.02),
      emotional (P=0.002), and spiritual LASA QOL scores (P=0.047). CONCLUSIONS:
      Caregivers of older adults with advanced cancer demonstrated better QOL and fewer
      mood disturbances compared to caregivers of younger patients. When patients have
      good QOL, caregivers also had good QOL.

PMID- 24726868
TI  - Italian Expert Panel on the management of patients with coexisting
      spondyloarthritis and inflammatory bowel disease.
AB  - Spondyloarthritis (SpA) is a group of diseases with similar clinical, radiologic
      and serologic features, including SpA associated with inflammatory bowel disease
      (IBD-associated SpA). Several studies have estimated the occurrence of SpA in IBD
      patients as ranging from 17% to 39%, confirming that SpA is the most frequent
      extra-intestinal manifestation in patients with IBD. In this paper, the expert
      panel presents some red flags to guide clinicians - both rheumatologists and
      gastroenterologists - to make a correct diagnosis of IBD-associated SpA in
      clinical practice. IBD-associated SpA classification, clinical presentation and
      diagnostic work-up are also presented. From the therapeutic point of view, only
      separate recommendations/guidelines are currently available for the treatment of
      Crohn's disease, ulcerative colitis and for both axial and peripheral SpA.
      However, when IBD and SpA coexist, the therapeutic strategy should be modulated
      to take into account the variable manifestations of IBD in terms of intestinal
      and extra-intestinal features, and the clinical manifestations of SpA, with
      particular attention to peripheral enthesitis, dactylitis and anterior uveitis.
      To our knowledge, this is the first attempt to define therapeutic algorithms for
      the integrated management of different IBD-associated SpA clinical scenarios. 

PMID- 24726864
TI  - Physiology and pathophysiology of iron in hemoglobin-associated diseases.
AB  - Iron overload and iron toxicity, whether because of increased absorption or iron
      loading from repeated transfusions, can be major causes of morbidity and
      mortality in a number of chronic anemias. Significant advances have been made in
      our understanding of iron homeostasis over the past decade. At the same time,
      advances in magnetic resonance imaging have allowed clinicians to monitor and
      quantify iron concentrations noninvasively in specific organs. Furthermore,
      effective iron chelators are now available, including preparations that can be
      taken orally. This has resulted in substantial improvement in mortality and
      morbidity for patients with severe chronic iron overload. This paper reviews the
      key points of iron homeostasis and attempts to place clinical observations in
      patients with transfusional iron overload in context with the current
      understanding of iron homeostasis in humans. 

PMID- 24726869
TI  - A novel in vitro co-culture system allows the concurrent analysis of mature
      biofilm and planktonic bacteria with human lung epithelia.
AB  - Pseudomonas aeruginosa establishes chronic infections by forming biofilms;
      however studies of the virulence have focused on the planktonic form. Few in
      vitro co-culture models exist to study biofilm infections. We present a novel in
      vitro co-culture method examining the interactions between mature P. aeruginosa
      biofilms and human lung epithelial cells. 

PMID- 24726870
TI  - Strain development and optimized fermentation conditions for blood meal using
      Aspergillus niger and Aspergillus oryzae.
AB  - To hydrolyze blood meal (BM) effectively, two mutants were generated using ultra
      violet mutagenesis. Single-factor experiments, the Plackett-Burman technique and
      response surface methodology were used to optimize the fermentation conditions.
      This study successfully generated a mutant and innovatively provided important
      parameters for utilizing BM by fermentation, which could be of industrial value. 

PMID- 24726871
TI  - Staphylococcus epidermidis biofilm quantification: effect of different solvents
      and dyes.
AB  - Staphylococcus epidermidis biofilm formed in the presence of the solvents DMSO,
      ethanol or methanol was quantified using safranin or crystal violet staining
      protocols. We found that biofilm quantification was the most accurate when
      safranin protocol was applied. Moreover, both DMSO and ethanol stimulated biofilm
      formation. 

PMID- 24726872
TI  - Evidence for the participation of peripheral alpha5 subunit-containing GABAA
      receptors in GABAA agonists-induced nociception in rats.
AB  - The activation of GABAA receptor by gamma-amino butyric acid (GABA) in primary
      afferent fibers produces depolarization. In normal conditions this depolarization
      causes a reduction in the release of neurotransmitters. Therefore, this
      depolarization remains inhibitory. However, previous studies have suggested that
      in inflammatory pain, GABA shifts its signaling from inhibition to excitation by
      an increased GABA-induced depolarization. The contribution of peripheral alpha5
      subunit-containing GABAA receptors to the inflammatory pain is unknown. The
      purpose of this study was to investigate the possible pronociceptive role of
      peripheral alpha5 subunit-containing GABAA receptors in the formalin test.
      Formalin (0.5%) injection into the dorsum of the right hind paw produced
      flinching behavior in rats. Ipsilateral local peripheral pre-treatment (-10min)
      with exogenous GABA (0.003-0.03ug/paw) or common GABAA receptor agonists muscimol
      (0.003-0.03ug/paw), diazepam (0.017-0.056ug/paw) or phenobarbital (1-100ug/paw)
      significantly increased 0.5% formalin-induced nociceptive behavior. The
      pronociceptive effects of GABA (0.03ug/paw), muscimol (0.03ug/paw), diazepam
      (0.056ug/paw) and phenobarbital (100ug/paw) were prevented by either the GABAA
      receptor antagonist bicuculline (0.01-0.1ug/paw) or selective alpha5 subunit
      containing GABAA receptor inverse agonist L-655,708 (0.017-0.17ug/paw). The
      alpha5 subunit-containing GABAA receptor protein was expressed in dorsal root
      ganglion (DRG) and dorsal spinal cord of naive rats. The formalin injection did
      not modify alpha5 subunit-containing GABAA receptor expression. Overall, these
      results suggest that peripheral alpha5 subunit-containing GABAA receptors play a
      pronociceptive role in the rat formalin test. 

PMID- 24726873
TI  - R-268712, an orally active transforming growth factor-beta type I receptor
      inhibitor, prevents glomerular sclerosis in a Thy1 nephritis model.
AB  - R-268712 is a novel and specific inhibitor of activin receptor-like kinase 5
      (ALK5), a transforming growth factor beta (TGF-beta) type I receptor. Evaluation
      of in vitro inhibition indicated that R-268712 is a potent and selective
      inhibitor of ALK5 with an IC50 of 2.5nM, an approximately 5000-fold more
      selectivity for ALK5 than p38 mitogen-activated protein kinase (MAPK). Oral
      administration of R-268712 at doses of 1, 3 and 10mg/kg also inhibited the
      development of renal fibrosis in a dose-dependent manner in a unilateral ureteral
      obstruction (UUO) model. Additionally, we evaluated the efficacy of R-268712 in a
      heminephrectomized anti-Thy1 glomerulonephritis model at doses of 0.3 and 1mg/kg.
      R-268712 reduced proteinuria and glomerulosclerosis significantly with
      improvement of renal function. Collectively, these results suggested that R
      268712 and other ALK5 inhibitors could suppress glomerulonephritis as well as
      glomerulosclerosis by an inhibitory mechanism that involves suppression of TGF
      beta signaling. 

PMID- 24726874
TI  - Aspirin-induced inhibition of adipogenesis was p53-dependent and associated with
      inactivation of pentose phosphate pathway.
AB  - Obesity has become a major public health problem of global significance. Today,
      aspirin remains the most commonly used medication for the treatment of pyrexia,
      pain, inflammation and antiplatelet. The present study aims at evaluating the
      possible existence of a putative p53-dependent pathway underlying the aspirin
      induced inhibition of adipogenesis. Cell migration assay was identified by the
      ability to migrate through Transwell insert. Oil Red O staining was employed to
      quantify adipose accumulation. The concentration of glucose and triglyceride were
      measured by using assay kits. The expression levels of several master regulatory
      molecules controlling various signal pathways were monitored using the
      immunoblotting techniques. Aspirin significantly inhibited preadipocyte migration
      and adipose accumulation. The p53-p21 signaling and the expression of
      differentiation marker glycerol-3-phosphate dehydrogenase were increased in a
      dose-dependent manner. It indicated that aspirin induced adipocyte
      differentiation through p53-p21 pathway. The oncogenic ERK 1/2 MAPK signaling was
      induced, whereas, the expression of adipogenic markers peroxisome proliferator
      activated receptor gamma (PPARgamma), adipocyte fatty acid-binding protein (A
      FABP) and inflammatory factors cyclooxygenase-2 (Cox-2), tumor necrosis factor
      alpha (TNFalpha) and inducible nitric oxide synthase (iNOS) were inhibited.
      Aspirin negatively regulated the pentose phosphate pathway (PPP) by inhibiting
      the expression of rate-limiting enzyme glucose-6-phosphate dehydrogenase.
      Knockdown the expression of oncogenic ERK 1/2 MAPK by using 10 MUM PD98059
      significantly increased triglyceride synthesis, adipose accumulation and
      activated PPP, however, decreased glucose uptake. Diverted the glucose flux to
      PPP, rather than increased glucose uptake, was associated with adipogenesis. Down
      regulated the expression of tumor suppressor p53 by 10 MUM pifithrin-alpha
      (PFTalpha) alone had no effect on adipose accumulation. However, administration
      of aspirin accompanied with PFTalpha abolished aspirin-induced inhibition of
      adipogenesis. We demonstrated that aspirin-induced inhibition of adipogenesis was
      p53-dependent and associated with inactivation of PPP. Blockade PPP may be a
      novel strategy for obesity prevention and therapy. Moreover, when use aspirin in
      therapeutic strategy, the p53 status should be considered.

PMID- 24726875
TI  - Heme oxygenase suppresses markers of heart failure and ameliorates cardiomyopathy
      in L-NAME-induced hypertension.
AB  - Heart failure and related cardiac complications remains a great health challenge.
      We investigated the effects of upregulating heme-oxygenase (HO) on myocardial
      histo-pathological lesions, proinflammatory cytokines/chemokines, oxidative
      mediators and important markers of heart failure such as osteopontin and
      osteoprotergerin in N(omega)-nitro-l-arginine methyl ester (L-NAME)-induced
      hypertension. Treatment with the HO-inducer, heme-arginate improved myocardial
      morphology in L-NAME hypertensive rats by attenuating subendocardial injury,
      interstitial fibrosis, mononuclear-cell infiltration and cardiomyocyte
      hypertrophy. These were associated with the reduction of several
      inflammatory/oxidative mediators including chemokines/cytokines such as
      macrophage inflammatory protein-1 alpha (MIP-1alpha), macrophage chemoattractant
      protein-1 (MCP-1), tumor necrosis factor alpha (TNF-alpha), interleukin (IL)-6,
      IL-1beta, endothelin-1, 8-isoprostane, nitrotyrosine, and aldosterone. Similarly,
      heme-arginate abated the elevated levels of extracellular matrix/remodeling
      proteins including transforming-growth factor beta (TGF-beta1) and collagen-IV in
      the myocardium. These were accompanied by significant reduction of proteins of
      heart failure such as osteopontin and osteoprotegerin. Interestingly, the cardio
      protective effects of heme-arginate were associated with the potentiation of
      adiponectin, atrial-natriuretic peptide (ANP), HO-1, HO-activity, cyclic
      gnanosine monophosphate (cGMP) and the total-anti-oxidant capacity, whereas the
      HO-inhibitor, chromium-mesoporphyrin nullified the effects of heme-arginate,
      exacerbating inflammatory injury and oxidative insults. We conclude that heme
      arginate therapy protects myocardial damage by potentiating the HO-adiponectin
      ANP axis, which in turn suppressed the elevated levels of aldosterone, pro
      inflammatory chemokines/cytokines, mononuclear-cell infiltration and oxidative
      stress, with concomitant reduction of extracellular matrix/remodeling proteins
      and heart failure proteins. These data suggest a cardio-protective role of the HO
      system against L-NAME-induced hypertension that could be explored in the design
      of novel strategies against cardiomyopathy. 

PMID- 24726876
TI  - Recruitment of phosphatase PP2A by RACK1 adaptor protein deactivates
      transcription factor IRF3 and limits type I interferon signaling.
AB  - The transcription factor IRF3 is a central regulator of type I interferon (IFN)
      signaling. The mechanisms underlying deactivation of IRF3 are poorly understood
      although many studies suggest that IRF3 activity is terminated through
      degradation after viral infection. Here we report that IRF3 is deactivated via
      dephosphorylation mediated by the serine and threonine phosphatase PP2A and its
      adaptor protein RACK1. The PP2A-RACK1 complex negatively regulated the IRF3
      pathway after LPS or poly(I:C) stimulation or Sendai virus (SeV) infection. After
      challenge with LPS, poly(I:C), or low-titer SeV, activated IRF3 was
      dephosphorylated and returned to resting state without being degraded, although
      high-titer SeV infection triggered the degradation of IRF3. Furthermore, PP2A
      deficient macrophages showed enhanced type I IFN signaling upon LPS, poly(I:C),
      and SeV challenge and protected mice from lethal vesicular stomatitis virus
      infection. Therefore, dephosphorylation of IRF3 is a deactivation mechanism that
      contributes to termination of IRF3-type I IFN signaling.

PMID- 24726877
TI  - Targeted prostaglandin E2 inhibition enhances antiviral immunity through
      induction of type I interferon and apoptosis in macrophages.
AB  - Aspirin gained tremendous popularity during the 1918 Spanish Influenza virus
      pandemic, 50 years prior to the demonstration of their inhibitory action on
      prostaglandins. Here, we show that during influenza A virus (IAV) infection,
      prostaglandin E2 (PGE2) was upregulated, which led to the inhibition of type I
      interferon (IFN) production and apoptosis in macrophages, thereby causing an
      increase in virus replication. This inhibitory role of PGE2 was not limited to
      innate immunity, because both antigen presentation and T cell mediated immunity
      were also suppressed. Targeted PGE2 suppression via genetic ablation of
      microsomal prostaglandin E-synthase 1 (mPGES-1) or by the pharmacological
      inhibition of PGE2 receptors EP2 and EP4 substantially improved survival against
      lethal IAV infection whereas PGE2 administration reversed this phenotype. These
      data demonstrate that the mPGES-1-PGE2 pathway is targeted by IAV to evade host
      type I IFN-dependent antiviral immunity. We propose that specific inhibition of
      PGE2 signaling might serve as a treatment for IAV.

PMID- 24726878
TI  - The enzyme Cyp26b1 mediates inhibition of mast cell activation by fibroblasts to
      maintain skin-barrier homeostasis.
AB  - Mast cells (MCs) mature locally, thus possessing tissue-dependent phenotypes for
      their critical roles in both protective immunity against pathogens and the
      development of allergy or inflammation. We previously reported that MCs highly
      express P2X7, a receptor for extracellular ATP, in the colon but not in the skin.
      The ATP-P2X7 pathway induces MC activation and consequently exacerbates the
      inflammation. Here, we identified the mechanisms by which P2X7 expression on MCs
      is reduced by fibroblasts in the skin, but not in the other tissues. The retinoic
      acid-degrading enzyme Cyp26b1 is highly expressed in skin fibroblasts, and its
      inhibition resulted in the upregulation of P2X7 on MCs. We also noted the
      increased expression of P2X7 on skin MCs and consequent P2X7- and MC-dependent
      dermatitis (so-called retinoid dermatitis) in the presence of excessive amounts
      of retinoic acid. These results demonstrate a unique skin-barrier homeostatic
      network operating through Cyp26b1-mediated inhibition of ATP-dependent MC
      activation by fibroblasts.

PMID- 24726879
TI  - Plastic surgery for breast conservation therapy: how to define the volume of the
      tumor bed for the boost?
AB  - PURPOSE: To describe the procedure of definition of the boost volume using pre-
      and post-operative computed tomography (CT) and surgical clips in the tumor bed
      after oncoplastic surgical procedure. PATIENTS AND METHODS: Thirty-one
      consecutive breast cancer patients who underwent simple lumpectomy or oncoplastic
      surgery were studied. All of them underwent pre- and post-operative CT scan in
      treatment position to evaluate the planning target volume (PTV) boost volume and
      define the primary tumor (gross tumor volume (GTV)) and tumor bed zones (CTV),
      with an overall margin of 5 mm in lateral and 10 mm in craniocaudal directions,
      corresponding to localization and setup uncertainties. RESULTS: Thirteem patients
      underwent simple lumpectomy and 18 oncoplastic surgery. The volumetric analysis
      showed that the intersection between GTV and CTV clips was significantly higher
      in patients with three and more clips (28.4% vs 3.14%; p < 0.001). In the case of
      patients with oncoplastic surgery, more than three clips were needed to define
      the tumor bed volume with accuracy. The number of clips was directly related to
      the exact definition of the boost volume. CONCLUSIONS: The use of more than three
      clips allows better definition of the PTV boost volume after oncoplastic surgical
      procedure.

PMID- 24726880
TI  - Effects of prenatal propofol exposure on postnatal development in rats.
AB  - Preclinical studies suggest that propofol may cause damage to immature neurons.
      However, the effect of maternal propofol exposure on the neuronal development of
      the offspring is largely unknown. In this study, pregnant rats were assigned to
      receive continuous infusion of saline (control) or propofol for 1 h (1HP) or 2 h
      (2HP) on gestational day 18. An additional group (lipid) was assigned to receive
      continuous infusion of intralipid fat emulsion (vehicle of propofol) for 2 h.
      Pups were then tested on the appearance and progression of sensory and physical
      motor abilities between postnatal day 1 (P1) and P28. The brain and body weights
      of pups from 2HP group on P10 were significantly lower than those from the saline
      control group, although they were the same in all four groups at birth (P0). Pups
      from 1HP and 2HP groups, but not lipid group, showed slower maturation of eyes
      (delayed opening) and several neurological reflexes (hindlimb reflex, righting
      reflex); they also showed delayed improvement in execution on gait reflex and
      inclined board tests. The forelimb reflex and negative geotaxis were also delayed
      in 2HP group. All parameters examined except body weight of 2HP pups recovered to
      normal levels by P28. We conclude that administration of propofol to pregnant
      rats leads to retardation in physical and neurological reflex development in
      their offspring.

PMID- 24726881
TI  - Overexpression of N-acetylglucosaminyltransferases III and V in human melanoma
      cells. Implications for MCAM N-glycosylation.
AB  - An important role in cancer pathogenesis is attributed to N-glycans with
      "bisecting" N-acetylglucosamine and beta1-6 branches but the exact mechanisms
      still remain to be elucidated. Two structures are formed by Golgi beta-1,4
      mannosyl-glycoprotein 4-beta-N-acetylglucosaminyltransferase (EC = 2.4.1.144, GnT
      III) and alpha-1,6-mannosylglycoprotein 6-beta-N-acetylglucosaminyltransferase A
      (EC = 2.4.1.155, GnT-V) respectively. The enzymes are encoded by MGAT3 and MGAT5
      genes. The aim of this study was to establish two human melanoma cell lines with
      induced overexpression of GnT-III or GnT-V and to perform a preliminary
      functional characterization. WM-266-4 cells were stably transfected with human
      MGAT3 or MGAT5 cDNAs. GnT-III and GnT-V activities were assayed with a novel HPLC
      method based on labeling of N-glycan acceptor with 2-aminobenzamide (adapted from
      Taniguchi et al., 1989). Higher expression and activities of glycosyltransferases
      were detected. Increased amounts of "bisected" and beta1-6 branched N-glycans
      were present on melanoma cell adhesion molecule (known as MCAM/MUC18). However,
      cells did not display significant differences in viability and capabilities to
      migrate through an endothelial layer. To the best of our knowledge, the result of
      our study is the first to demonstrate that "bisected" N-glycans can be carried by
      MCAM. Moreover, increased modification of this protein by the two
      glycosyltransferases in WM-266-4-GnT-III cells was the consequence of the
      overexpression of only one enzyme. The obtained model can be useful for studying
      mechanisms of N-glycans branching and better understanding of their role in
      cancer progression. The proposed modification of the glycosyltransferase activity
      assay has shown to be a good alternative for 2-aminopyridine based HPLC systems.

PMID- 24726882
TI  - Induction of ATM/ATR pathway combined with Vgamma2Vdelta2 T cells enhances
      cytotoxicity of ovarian cancer cells.
AB  - Many ovarian cancer cells express stress-related molecule MICA/B on their surface
      that is recognized by Vgamma2Vdelta2 T cells through their NKG2D receptor, which
      is transmitted to downstream stress-signaling pathway. However, it is yet to be
      established how Vgamma2Vdelta2 T cell-mediated recognition of MICA/B signal is
      transmitted to downstream stress-related molecules. Identifying targeted
      molecules would be critical to develop a better therapy for ovarian cancer cells.
      It is well established that ATM/ATR signal transduction pathways, which is
      modulated by DNA damage, replication stress, and oxidative stress play central
      role in stress signaling pathway regulating cell cycle checkpoint and apoptosis.
      We investigated whether ATM/ATR and its down stream molecules affect
      Vgamma2Vdelta2 T cell-mediated cytotoxicity. Herein, we show that ATM/ATR pathway
      is modulated in ovarian cancer cells in the presence of Vgamma2Vdelta2 T cells.
      Furthermore, downregulation of ATM pathway resulted downregulation of MICA, and
      reduced Vgamma2Vdelta2 T cell-mediated cytotoxicity. Alternately, stimulating ATM
      pathway enhanced expression of MICA, and sensitized ovarian cancer cells for
      cytotoxic lysis by Vgamma2Vdelta2 T cells. We further show that combining
      currently approved chemotherapeutic drugs, which induced ATM signal transduction,
      along with Vgamma2Vdelta2 T cells enhanced cytotoxicity of resistant ovarian
      cancer cells. These findings indicate that ATM/ATR pathway plays an important
      role in tumor recognition, and drugs promoting ATM signaling pathway might be
      considered as a combination therapy together with Vgamma2Vdelta2 T cells for
      effectively treating resistant ovarian cancer cells. 

PMID- 24726883
TI  - Fatty acids are novel nutrient factors to regulate mTORC1 lysosomal localization
      and apoptosis in podocytes.
AB  - Podocyte apoptosis is a potent mechanism of proteinuria in diabetic nephropathy.
      More detailed mechanistic insight into podocyte apoptosis is needed to better
      understand the pathogenesis of diabetic nephropathy. An elevated level of serum
      free fatty acid (FFA), as well as hyperglycemia, is a clinical characteristic in
      diabetes, although its causal role in podocyte apoptosis remains unclear. This
      study examined the effect of three types of FFAs, saturated, monounsaturated and
      polyunsaturated FFAs, on podocyte apoptosis. Palmitate, a saturated FFA, induced
      endoplasmic reticulum (ER) stress-dependent apoptosis in podocytes. Oleate, a
      monounsaturated FFA, and eicosapentaenoic acid (EPA), an omega-3 polyunsaturated
      FFA did not induce apoptosis; rather, they antagonized palmitate-induced
      apoptosis. Palmitate activated mammalian target of rapamycin (mTOR) complex 1
      (mTORC1), a nutrient-sensing kinase regulating a wide range of cell biology.
      Furthermore, inhibition of mTORC1 activity by rapamycin or siRNA for Raptor, a
      component of mTORC1, ameliorated palmitate-induced ER stress and apoptosis in
      podocytes. Activity of mTORC1 is regulated by upstream kinases and Rag/Ragulator
      dependent recruitment of mTOR onto lysosomal membranes. Palmitate activated
      mTORC1 by enhancing recruitment of mTOR onto lysosomal membranes, which was
      inhibited by co-incubation with oleate or EPA. Inhibition of mTOR translocation
      onto lysosomes by transfection with dominant-negative forms of Rag ameliorated
      palmitate-induced apoptosis. This study suggests that saturated and unsaturated
      FFAs have opposite effects on podocyte apoptosis by regulating mTORC1 activity
      via its translocation onto lysosomal membranes, and the results provide a better
      understanding of the pathogenesis in diabetic nephropathy and a novel role of
      mTORC1 in cell apoptosis. 

PMID- 24726885
TI  - Dual contribution of MAPK and PI3K in epidermal growth factor-induced
      destabilization of thyroid follicular integrity and invasion of cells into
      extracellular matrix.
AB  - Normal thyrocytes grown as reconstituted follicles in collagen gel were evaluated
      for drug effects of small molecule kinase inhibitors on growth factor-induced
      cell migration in a 3D context. MEK inhibition by U0126 only partially
      antagonized EGF/serum-induced cell migration from the basal follicular surface
      into the matrix. Combined treatment with U0126 and LY294002, a PI3K blocker, was
      necessary to abolish migration. However, exposure to only LY294002 facilitated
      the response to EGF by breakdown of the original follicular structure. In the
      same time EGF promoted thyroid cell survival that was compromised by LY294002 in
      absence of EGF. Cells treated with EGF and LY294002 retained the ability to form
      follicles. The findings indicate that dual inhibition of MAPK and PI3K/AKT
      pathways is required to fully block matrix invasion of EGF-stimulated thyroid
      cells. Conversely, single drug treatment with PI3K inhibitor adversely promotes
      invasiveness probably by destabilizing the follicular epithelium. 

PMID- 24726884
TI  - DNA damage response in renal ischemia-reperfusion and ATP-depletion injury of
      renal tubular cells.
AB  - Renal ischemia-reperfusion leads to acute kidney injury (AKI) that is
      characterized pathologically by tubular damage and cell death, followed by
      tubular repair, atrophy and interstitial fibrosis. Recent work suggested the
      possible presence of DNA damage response (DDR) in AKI. However, the evidence is
      sketchy and the role and regulation of DDR in ischemic AKI remain elusive. In
      this study, we demonstrated the induction of phosphorylation of ATM, H2AX, Chk2
      and p53 during renal ischemia-reperfusion in mice, suggesting DDR in kidney
      tissues. DDR was also induced in vitro during the recovery or "reperfusion" of
      renal proximal tubular cells (RPTCs) after ATP depletion. DDR in RPTCs was
      abrogated by supplying glucose to maintain ATP via glycolysis, indicating that
      the DDR depends on ATP depletion. The DDR was also suppressed by the general
      caspase inhibitor z-VAD and the overexpression of Bcl-2, supporting a role of
      apoptosis-associated DNA damage in the DDR. N-acetylcysteine (NAC), an
      antioxidant, suppressed the phosphorylation of ATM and p53 and, to a less extent,
      Chk2, but NAC increased the phosphorylation and nuclear foci formation of H2AX.
      Interestingly, NAC increased apoptosis, which may account for the observed H2AX
      activation. Ku55933, an ATM inhibitor, blocked ATM phosphorylation and
      ameliorated the phosphorylation of Chk2 and p53, but it increased H2AX
      phosphorylation and nuclear foci formation. Ku55933 also increased apoptosis in
      RPTCs following ATP depletion. The results suggest that DDR occurs during renal
      ischemia-reperfusion in vivo and ATP-depletion injury in vitro. The DDR is
      partially induced by apoptosis and oxidative stress-related DNA damage. ATM, as a
      sensor in the DDR, may play a cytoprotective role against tubular cell injury and
      death. 

PMID- 24726886
TI  - Therapeutic efficacy of improved alpha-fetoprotein promoter-mediated tBid
      delivered by folate-PEI600-cyclodextrin nanopolymer vector in hepatocellular
      carcinoma.
AB  - SNPs in human AFP promoter are associated with serum AFP levels in hepatocellular
      carcinoma (HCC), suggesting that AFP promoter variants may generate better
      transcriptional activities while retaining high specificity to AFP-producing
      cells. We sequenced human AFP promoters, cloned 15 different genotype promoters
      and tested their reporter activities in AFP-producing and non-producing cells.
      Among various AFP variant fragments tested, EA4D exhibited the highest reporter
      activity and thus was selected for the further study. EA4D was fused with tBid
      and coupled with nano-particle vector (H1) to form pGL3-EA4D-tBid/H1. pGL3-EA4D
      tBid/H1 could express a high level of tBid while retain the specificity to AFP
      producing cells. In a HCC tumor model, application of pGL3-EA4D-tBid/H1
      significantly inhibited the growth of AFP-producing-implanted tumors with minimal
      side-effects, but had no effect on non-AFP-producing tumors. Furthermore, pGL3
      EA4D-tBid/H1 could significantly sensitize HCC cells to sorafenib, an approved
      anti-HCC agent. Collectively, pGL3-EA4D-tBid/H1, a construct with the AFP
      promoter EA4D and the novel H1 delivery system, can specifically target and
      effectively suppress the AFP-producing HCC. This new therapeutic tool shows
      little toxicity in vitro and in vivo and it should thus be safe for further
      clinical tests. 

PMID- 24726888
TI  - Identification of new synthetic PDE-5 inhibitors analogues found as minor
      components in a dietary supplement.
AB  - A dietary supplement sold in erotic shops was analysed. It contains
      dithiodesmethylcarbodenafil as the major component, which was already reported as
      an adulterant in dietary supplements. Additionally three more compounds were
      found and their structures were elucidated after isolation using NMR and mass
      spectroscopy. They were designated as isonitrosoprodenafil,
      dithiodesethylcarbodenafil and norcarbodenafil. 

PMID- 24726887
TI  - Ventricular myosin modifies in vitro step-size when phosphorylated.
AB  - Cardiac and skeletal muscle myosins have the central role in contraction
      transducing ATP free energy into the mechanical work of moving actin. Myosin has
      a motor domain containing ATP and actin binding sites and a lever-arm that
      undergoes rotation impelling bound actin. The lever-arm converts torque generated
      in the motor into the linear displacement known as step-size. The myosin lever
      arm is stabilized by bound essential and regulatory light chains (ELC and RLC).
      RLC phosphorylation at S15 is linked to modified lever-arm mechanical
      characteristics contributing to myosin filament based contraction regulation and
      to the response of the muscle to disease. Myosin step-size was measured using a
      novel quantum dot (Qdot) assay that previously confirmed a 5nm step-size for fast
      skeletal myosin and multiple unitary steps, most frequently 5 and 8nm, and a rare
      3nm displacement for beta cardiac myosin (betaMys). S15 phosphorylation in
      betaMys is now shown to change step-size distribution by advancing the 8nm step
      frequency. After phosphorylation, the 8nm step is the dominant myosin step-size
      resulting in significant gain in the average step-size. An increase in myosin
      step-size will increase the amount of work produced per ATPase cycle. The results
      indicate that RLC phosphorylation modulates work production per ATPase cycle
      suggesting the mechanism for contraction regulation by the myosin filament. 

PMID- 24726889
TI  - Degradation pathways study of the natriuretic and beta-adrenoceptor antagonist
      tienoxolol using liquid chromatography-electrospray ionization multistage mass
      spectrometry.
AB  - Tienoxolol is a pharmacologically active molecule designed with the functional
      groups ketothiophene, alkyl benzoate and arylpropanolamine so as to combine a
      diuretic and a beta-adrenoreceptor antagonist into a single molecule. Its
      degradation products generated in several stress media have been determined by
      high-pressure liquid chromatography (HPLC) coupled to a hybrid mass spectrometer
      with a triple quadrupole-linear trap. A Polaris((r)) column with a C18-A
      stationary phase and a linear gradient mobile phase composed of a mixture of
      trifluoroacetic acid 1% (v/v) and acetonitrile allowed for optimal separation.
      Structural elucidation of the degradation products has been based on MS/MS
      techniques, by comparing their fragmentation patterns to the precursor's data. Up
      to seven degradation products of the active ingredient, resulting from
      hydrolysis, oxidation, dehydration and transamidation have been identified,
      covering a range of possible degradation pathways for derivatives with such
      functional groups. Kinetics have been studied to assess the molecule's shelf life
      and to identify the most important degradation factor. 

PMID- 24726890
TI  - Adropin: a new regulatory peptide in cardiovascular endocrinology.

PMID- 24726891
TI  - The diagnostic and grading value of diffusion tensor imaging in patients with
      carpal tunnel syndrome.
AB  - RATIONALE AND OBJECTIVES: In this study, we investigated the diagnostic and
      grading value of diffusion tensor imaging (DTI) in patients with carpal tunnel
      syndrome (CTS). MATERIALS AND METHODS: Of the 120 subjects included in the
      present study, 72 were in the CTS group and 48 were in the healthy control group.
      In addition, the patients with CTS were further divided into three subgroups
      based on severity (mild, moderate, and severe) according to electrophysiological
      studies (EPS). DTI-derived parameters (fractional anisotropy [FA] and apparent
      diffusion coefficient [ADC]) were evaluated at four median nerve levels. The mean
      FA and ADC values of the CTS groups and healthy controls were compared
      separately. Correlations and possible relationships between DTI parameters and
      EPS results were analyzed. Receiver operating characteristics analysis was used
      to calculate the FA and ADC cutoff values for CTS diagnosis and grading. RESULTS:
      Statistically significant differences were observed in mean FA and ADC between
      the normal and mild, mild and moderate, and moderate and severe subgroups.
      Significant correlations were found between DTI parameters and EPS measurements
      based on severity. FA and ADC threshold values, as well as the sensitivity and
      specificity levels, for diagnosing and grading CTS were determined. CONCLUSIONS:
      DTI parameters can provide helpful information for CTS. The correlations of FA
      and ADC measurements versus EPS measurements based on severity were significant.
      Moreover, FA and ADC threshold values were sufficient for the diagnosis and
      grading of CTS.

PMID- 24726892
TI  - Neurophobia: a global and under-recognized phenomenon.

PMID- 24726893
TI  - The primary cilium influences interleukin-1beta-induced NFkappaB signalling by
      regulating IKK activity.
AB  - The primary cilium is an organelle acting as a master regulator of cellular
      signalling. We have previously shown that disruption of primary cilia assembly,
      through targeting intraflagellar transport, is associated with muted nitric oxide
      and prostaglandin responses to the inflammatory cytokine interleukin-1beta (IL
      1beta). Here, we show that loss of the primary cilium disrupts specific molecular
      signalling events in cytosolic NFkappaB signalling. The induction of
      cyclooxygenase 2 (COX2) and inducible nitrous oxide synthase (iNOS) protein is
      abolished. Cells unable to assemble cilia exhibit unaffected activation of
      IkappaB kinase (IKK), but delayed and reduced degradation of IkappaB, due to
      diminished phosphorylation of inhibitor of kappa B (IkappaB) by IKK. This results
      in both delayed and reduced NFkappaB p65 nuclear translocation and nuclear
      transcript binding. We also demonstrate that heat shock protein 27 (hsp27), an
      established regulator of IKK, is localized to the ciliary axoneme and cellular
      levels are dramatically disrupted with loss of the primary cilium. These results
      suggest that the primary cilia compartment exerts influence over NFkappaB
      signalling. We propose that the cilium is a locality for regulation of the
      molecular events defining NFkappaB signalling events, tuning signalling as
      appropriate. 

PMID- 24726894
TI  - The prolyl isomerase Pin1 regulates hypoxia-inducible transcription factor (HIF)
      activity.
AB  - Hypoxia-inducible transcription factor-1 (HIF-1) plays a decisive role in cell
      survival and adaptation to hypoxic stress by controlling the expression of genes
      involved in oxygen homeostasis. HIF-1 activity is fine-tuned through specific
      post-translational modifications of its essential HIF-1alpha subunit. Among these
      modifications, phosphorylation is important for HIF-1 transcriptional activity.
      Studies have shown that the mitogen-activated protein kinases, p42/p44 MAPKs,
      directly phosphorylate HIF-1alpha and increase HIF-1-mediated transcription.
      Pin1, a peptidyl-prolyl cis/trans isomerase, targets a number of proteins
      containing a phosphorylated Ser/Thr-Pro motif. Pin1 isomerization causes a change
      in target protein conformation which can modify their activity. Here, we identify
      Pin1 as an important HIF-1alpha partner. Immunoprecipitation and pull-down
      studies show that Pin1 interacts with HIF-1alpha. We demonstrate that the
      interaction between Pin1 and HIF-1alpha is regulated through p42/p44 MAPK pathway
      activation. By performing proteolysis studies, our results indicate that Pin1
      catalytic activity generates a conformational change in HIF-1alpha. Finally, our
      work shows that Pin1 is required for gene-specific HIF-1 transcriptional
      activity. Our results indicate that the prolyl isomerase Pin1 regulates HIF-1
      transcriptional activity by interacting with HIF-1alpha and promoting
      conformational changes in a p42/p44 MAPK phosphorylation-dependent manner. 

PMID- 24726897
TI  - AAG8 promotes carcinogenesis by activating STAT3.
AB  - Dysregulation of signalling pathways by changes of gene expression contributes to
      hallmarks of cancer. The ubiquitously expressed chaperone protein AAG8 (aging
      associated gene 8 protein, encoded by the SIGMAR1 gene) is often found to be
      overexpressed in various cancers. AAG8 is involved in ER (endoplasmic reticulum)
      associated degradation and has been intensively elaborated in neuroscience.
      However, its rationale in carcinogenesis has rarely been noticed. In this study,
      we explored the intrinsic oncogenetic roles of AAG8 in cancer cells and found
      that AAG8 promoted carcinogenesis both in vitro and in vivo. We further
      characterized AAG8, for the first time to our knowledge, as a STAT3 activator and
      elucidated that it alternatively activated STAT3 in addition to IL6/JAK pathway.
      Based on these findings and a drug screening study, we demonstrated that combined
      inhibition of AAG8 and IL6/JAK signalling synergistically limits cancer cell
      growth. Taken together, our findings shed light on the fundamental evidences for
      identification of AAG8 as an oncoprotein and potential target for cancer
      prevention, as well as highlight the importance of ER proteins in contributing to
      JAK/STAT signaling and carcinogenesis.

PMID- 24726896
TI  - Ubiquitination-dependent CARM1 degradation facilitates Notch1-mediated podocyte
      apoptosis in diabetic nephropathy.
AB  - Podocyte apoptosis induced by hyperglycemia is considered a critical factor in
      the development of diabetic nephropathy. Recent studies have implicated Notch
      signaling in podocyte apoptosis; however, its regulatory mechanisms are not fully
      understood. In this study, we found that high-glucose treatment increased Notch1
      and Jagged-1 expression, the transcriptional activity of Hes, and podocyte
      apoptosis, and decreased the expression of coactivator-associated arginine
      methyltransferase 1 (CARM1) in rat podocytes. Transient transfection of CARM1
      reversed high-glucose-induced Notch1 expression, the transcriptional activity of
      Hes, and podocyte apoptosis. Moreover, the silencing of CARM1 using siRNA
      increased Notch1 expression, the transcriptional activity of Hes, and podocyte
      apoptosis. However, the Glu(266)-mediated enzymatic activity of CARM1 was not
      necessary for Notch signaling activation and podocyte apoptosis. Here, we
      demonstrate that AMP-activated protein kinase alpha (AMPKalpha) and cannabinoid
      receptor 1 (CB1R) are regulated by CARM1 and that high-glucose-induced podocyte
      apoptosis is mediated by a CARM1-AMPKalpha-Notch1-CB1R signaling axis. We also
      show that high-glucose-induced CARM1 downregulation is due to ubiquitination
      dependent CARM1 degradation. Finally, we demonstrate that CARM1 expression in
      podocytes was diminished in rats with streptozotocin-induced diabetes compared to
      vehicle-treated rats. Together, our data provide evidence that ubiquitination
      dependent CARM1 degradation in podocytes in diabetes promotes podocyte apoptosis
      via Notch1 activation. Strategies to preserve CARM1 expression or reduce the
      enzymatic activity of a ubiquitin ligase specific for CARM1 could be used to
      prevent podocyte loss in diabetic nephropathy.

PMID- 24726895
TI  - Activation of AMPK and inactivation of Akt result in suppression of mTOR-mediated
      S6K1 and 4E-BP1 pathways leading to neuronal cell death in in vitro models of
      Parkinson's disease.
AB  - Parkinson's disease (PD) is a neurodegenerative disorder characterized by loss of
      dopaminergic neurons. Dysregulation of mammalian target of rapamycin (mTOR) has
      been implicated in the pathogenesis of PD. However, the underlying mechanism is
      incompletely elucidated. Here, we show that PD mimetics (6-hydroxydopamine, N
      methyl-4-phenylpyridine or rotenone) suppressed phosphorylation of mTOR, S6K1 and
      4E-BP1, reduced cell viability, and activated caspase-3 and PARP in PC12 cells
      and primary neurons. Overexpression of wild-type mTOR or constitutively active
      S6K1, or downregulation of 4E-BP1 in PC12 cells partially prevented cell death in
      response to the PD toxins, revealing that mTOR-mediated S6K1 and 4E-BP1 pathways
      due to the PD toxins were inhibited, leading to neuronal cell death. Furthermore,
      we found that the inhibition of mTOR signaling contributing to neuronal cell
      death was attributed to suppression of Akt and activation of AMPK. This is
      supported by the findings that ectopic expression of constitutively active Akt or
      dominant negative AMPKalpha, or inhibition of AMPKalpha with compound C partially
      attenuated inhibition of phosphorylation of mTOR, S6K1 and 4E-BP1, activation of
      caspase-3, and neuronal cell death triggered by the PD toxins. The results
      indicate that PD stresses activate AMPK and inactivate Akt, causing neuronal cell
      death via inhibiting mTOR-mediated S6K1 and 4E-BP1 pathways. Our findings suggest
      that proper co-manipulation of AMPK/Akt/mTOR signaling may be a potential
      strategy for prevention and treatment of PD. 

PMID- 24726899
TI  - Pathology of human plaque vulnerability: mechanisms and consequences of
      intraplaque haemorrhages.
AB  - Atherothrombotic diseases are still major causes of inability and mortality and
      fighting atherothrombosis remains a public health priority. The involvement of
      repeated intraplaque haemorrhages (IPH) in the evolution of atherothrombotic
      lesions towards complications was proposed as early as 1936. This important topic
      has been recently revisited and reviewed. Histological observations have been
      corroborated by magnetic resonance imaging (MRI) of human carotid atheroma,
      identifying IPH as the main determinant of plaque evolution towards rupture.
      Beside the intimal integration of asymptomatic luminal coagulum, inward sprouting
      of neovessels from the adventitia towards the plaque, is one source of IPH in
      human atheroma. We recently described that directed neo-angiogenesis from the
      adventitia towards the plaque, across the media, is initiated by lipid mediators
      generated by the plaque on the luminal side, outwardly convected to the medial
      VSMCs. Subsequent stimulation of VSMC PPAR-gamma receptors induces VEGF
      expression which causes centripetal sprouting of adventitial vessels. However,
      this neovascularization is considered to be immature and highly susceptible to
      leakage. The main cellular components of IPH are Red Blood Cells (RBCs), which
      with their haemoglobin content and their cell membrane components, particularly
      enriched in unesterified cholesterol, participate in both the oxidative process
      and cholesterol accumulation. The presence of iron, glycophorin A and ceroids
      provides evidence of RBCs. IPH also convey blood leukocytes and platelets and are
      sites prone to weak pathogen contamination. Therefore prevention and treatment of
      the biological consequences of IPH pave the way to innovative preventive
      strategies and improved therapeutic options in human atherothrombotic diseases.

PMID- 24726898
TI  - Inhibition of human insulin gene transcription and MafA transcriptional activity
      by the dual leucine zipper kinase.
AB  - Insulin biosynthesis is an essential beta-cell function and inappropriate insulin
      secretion and biosynthesis contribute to the pathogenesis of diabetes mellitus
      type 2. Previous studies showed that the dual leucine zipper kinase (DLK) induces
      beta-cell apoptosis. Since beta-cell dysfunction precedes beta-cell loss, in the
      present study the effect of DLK on insulin gene transcription was investigated in
      the HIT-T15 beta-cell line. Downregulation of endogenous DLK increased whereas
      overexpression of DLK decreased human insulin gene transcription. 5'- and 3'
      deletion human insulin promoter analyses resulted in the identification of a DLK
      responsive element that mapped to the DNA binding-site for the beta-cell specific
      transcription factor MafA. Overexpression of DLK wild-type but not its kinase
      dead mutant inhibited MafA transcriptional activity conferred by its
      transactivation domain. Furthermore, in the non-beta-cell line JEG DLK inhibited
      MafA overexpression-induced human insulin promoter activity. Overexpression of
      MafA and DLK or its kinase-dead mutant into JEG cells revealed that DLK but not
      its mutant reduced MafA protein content. Inhibition of the down-stream DLK kinase
      c-Jun N-terminal kinase (JNK) by SP600125 attenuated DLK-induced MafA loss.
      Furthermore, mutation of the serine 65 to alanine, shown to confer MafA protein
      stability, increased MafA-dependent insulin gene transcription and prevented DLK
      induced MafA loss in JEG cells. These data suggest that DLK by activating JNK
      triggers the phosphorylation and degradation of MafA thereby attenuating insulin
      gene transcription. Given the importance of MafA for beta-cell function, the
      inhibition of DLK might preserve beta-cell function and ultimately retard the
      development of diabetes mellitus type 2.

PMID- 24726900
TI  - The trees and the forest: Characterization of complex brain networks with minimum
      spanning trees.
AB  - In recent years there has been a shift in focus from the study of local, mostly
      task-related activation to the exploration of the organization and functioning of
      large-scale structural and functional complex brain networks. Progress in the
      interdisciplinary field of modern network science has introduced many new
      concepts, analytical tools and models which allow a systematic interpretation of
      multivariate data obtained from structural and functional MRI, EEG and MEG.
      However, progress in this field has been hampered by the absence of a simple,
      unbiased method to represent the essential features of brain networks, and to
      compare these across different conditions, behavioural states and
      neuropsychiatric/neurological diseases. One promising solution to this problem is
      to represent brain networks by a minimum spanning tree (MST), a unique acyclic
      subgraph that connects all nodes and maximizes a property of interest such as
      synchronization between brain areas. We explain how the global and local
      properties of an MST can be characterized. We then review early and more recent
      applications of the MST to EEG and MEG in epilepsy, development, schizophrenia,
      brain tumours, multiple sclerosis and Parkinson's disease, and show how MST
      characterization performs compared to more conventional graph analysis. Finally,
      we illustrate how MST characterization allows representation of observed brain
      networks in a space of all possible tree configurations and discuss how this may
      simplify the construction of simple generative models of normal and abnormal
      brain network organization.

PMID- 24726901
TI  - Steroid-induced oocyte maturation in Indian shad Tenualosa ilisha (Hamilton,
      1822) is dependent on phosphatidylinositol 3 kinase but not MAP kinase
      activation.
AB  - Fully grown fish and amphibian oocytes exposed to a maturation-inducing steroid
      (MIS) activates multiple signal transduction pathways, leading to formation and
      activation of maturation-promoting factor (MPF) and induction of germinal vesicle
      breakdown (GVBD). The present study was to investigate if phosphatidylinositol 3
      kinase (PI3 kinase) and mitogen-activated protein kinase (MAP kinase) activation
      are required for naturally occurring MIS, 17alpha,20beta-dihydroxy-4-pregnen-3
      one (17,20beta-P)-induced cdc2 activation and oocyte maturation (OM) in Tenualosa
      ilisha. We observed that 17,20beta-P-induced OM was significantly inhibited by
      PI3 kinase inhibitors Wortmannin and LY29400. 17,20 beta-P was shown to activate
      PI3 kinase maximally at 90 min and cdc2 kinase at 16 h of treatment. Relative
      involvement of PI3 kinase, MAP kinase and cdc2 kinase in 17,20beta-P-induced OM
      was examined. MAP kinase was rapidly phosphorylated and activated (60-120 min)
      after MIS treatment and this response preceded the activation of cdc2 kinase by
      several hours. A selective inhibitor of MAP kinase (MEK), PD98059, sufficiently
      blocked the phosphorylation and activation of MAP kinase. Inhibition of MAP
      kinase activity using PD98059 however, had no effect on MIS-induced cdc2 kinase
      activation and GVBD. These results demonstrate that activation of the PI3 kinase
      is required for 17,20beta-P-induced cdc2 kinase activation and OM in T. ilisha.
      MAP kinase although was activated in response to 17,20beta-P and PI3 kinase
      activation, it is not necessary for cdc2 activation and OM in this species.

PMID- 24726902
TI  - Identification of naive HVC-4 patients who may be treated with pegylated
      interferon and ribavirin according to IL28B polymorphisms.
AB  - BACKGROUND: The current treatment of HCV-4 patients is dual therapy with PEG-IFN
      and ribavirin; however, new drugs against this genotype will be available within
      few months. Despite the evidenced good virological response in IFN-free regimens,
      the high cost of these new therapies will require patient selection. In our paper
      we propose the use of both rs8099917 and rs12979860 IL28-B polymorphisms, in
      order to identify potentially categories of SVR, null-responder and relapse and
      consequently to choose the dual therapy or novel approach. METHODS: One hundred
      and sixty-nine patients with chronic hepatitis C and genotype 4 treated with
      pegylated interferon and ribavirin for 48weeks were retrospectively studied. All
      patients were genotyped for rs8099917 and rs12979860 interleukin-28B
      polymorphisms. RESULTS: 80 patients with SVR (88.8%) had the TT/CC or TT/TC
      (rs8099917/rs12979860) (p<0.001) genotypes; the null-responders (n=13), 9 (69.2%)
      showed the GG/TT allelic distribution (p<0.001); relapsers showed a prevalent
      distribution of the TG/TC genotype (83.3%) (p<0.001). The 6 (100%) breakthrough
      patients showed TT/TC genotype, while the partial responders patients did not
      show any particular IL-28B genetic profile. Genetic profiles different from TT/CC
      showed 94.9% negative predictive value for SVR, with 92.6% of sensitivity and
      65.2% of specificity. Insulin-resistance, diabetes and liver fibrosis were not
      relevant in our multivariate analysis. CONCLUSIONS: The combination of both
      rs8099917/rs12979860 polymorphisms is useful for early identification of SVR,
      null-responders and relapsers. This could be used to chose between standard dual
      therapy or novel approach with IFN-free regimens.

PMID- 24726903
TI  - Ultraweak photon emission and proteomics analyses in soybean under abiotic
      stress.
AB  - Biophotons are ultraweak photon emissions that are closely related to various
      biological activities and processes. In mammals, biophoton emissions originate
      from oxidative bursts in immunocytes during immunological responses. Biophotons
      emitted from plant organs provide novel information about the physiological state
      of plant under in vivo condition. In this review, the principles and recent
      advances in the measurement of biophoton emissions in plants are described.
      Furthermore, examples of biophoton emission and proteomics in soybean under
      abiotic stress are reviewed and discussed. Finally, this review suggests that the
      application of proteomics should provide a better interpretation of plant
      response to biophoton emission and allow the identification of genes that will
      allow the screening of crops able to produce maximal yields, even in stressful
      environments. 

PMID- 24726904
TI  - Are patients with inflammatory bowel diseases at increased risk for
      cardiovascular disease?

PMID- 24726905
TI  - The taller they come: height and esophageal adenocarcinoma.

PMID- 24726906
TI  - Proton pump inhibitors reduce the size and acidity of the acid pocket in the
      stomach.
AB  - BACKGROUND & AIMS: The gastric acid pocket is believed to be the reservoir from
      which acid reflux events originate. Little is known about how changes in
      position, size, and acidity of the acid pocket contribute to the therapeutic
      effect of proton pump inhibitors (PPIs) in patients with gastroesophageal reflux
      disease (GERD). METHODS: Thirty-six patients with GERD (18 not taking PPIs, 18
      taking PPIs; 19 men; age, 55 +/- 2.1 y) were analyzed by concurrent high
      resolution manometry and pH-impedance monitoring after a standardized meal. The
      acid pocket was visualized using scintigraphy after intravenous administration of
      (99m)technetium-pertechnetate. The size of the acid pocket was measured and its
      position was determined, relative to the diaphragm, using radionuclide markers on
      a high-resolution manometry catheter. At the end of the study, the acid pocket
      was aspirated, and its pH level was measured. RESULTS: The number of reflux
      episodes was comparable between patients on and off PPIs, but the number of acid
      reflux episodes was reduced significantly in patients on PPIs. In patients on
      PPIs, the acid pocket was smaller and more frequently located below the
      diaphragm. The mean pH of the acid pocket was significantly lower in patients not
      taking PPIs (n = 6) than in those who were (n = 16) (0.9; range, 0.7-1.2 vs 4.0;
      range, 1.6-5.9; P < .001). The pH of acid pockets correlated significantly with
      the lowest pH values measured for refluxate (r = 0.72; P < .01). CONCLUSIONS:
      Based on analyses of acid pockets in patients with GERD, the acid pocket appears
      to be a reservoir from which reflux occurs when patients are receiving PPIs. PPIs
      might affect the size, acidity, or position of the acid pocket, which contributes
      to the efficacy in patients with GERD.

PMID- 24726907
TI  - Effects of inflammatory bowel disease on students' adjustment to college.
AB  - BACKGROUND & AIMS: Successful adjustment to college is required for academic
      success. We investigated whether inflammatory bowel disease (IBD) activity
      affects this adjustment process. METHODS: We created an online survey that
      included a Student Adaptation to College Questionnaire (SACQ), a general quality
      of life survey (SF-12), a disease-specific short IBD quality of life survey
      (SIBDQ), and disease activity indices. Undergraduate students across the United
      States were recruited via social media. RESULTS: Surveys were completed by 65
      students with Crohn's disease (CD), 28 with ulcerative colitis, and 214 healthy
      students (controls). Disease-specific quality of life (SIBDQ results) correlated
      with IBD disease activity (rho = -0.79; P < .0001). High college adjustment
      scores (SACQ results) were associated with high SIBDQ scores. Students with IBD
      had lower mean SACQ scores than controls (307 vs 290; P < .0001). There was a
      modest inverse correlation between CD activity and SACQ (rho = -0.24; P < .04).
      Disease activity in students with CD was associated strongly with their self
      reported ability to keep up with academic work (P < .0089) and confidence in
      their ability to meet future academic challenges (P < .0015). Students with
      active IBD reported feeling as if they were not academically successful (P <
      .018), and students with ulcerative colitis reported irregular class attendance
      (P < .043). CONCLUSIONS: Students with IBD do not adjust to college as well as
      healthy students. Disease activity affects their adjustment and attitudes about
      academics-especially among students with CD. Successful adjustment is important
      for academic success, affecting graduation rates and future economic success.
      Strategies to increase disease control and provide social and emotional support
      during college could improve adjustment to college and academic performance, and
      increase patients' potential.

PMID- 24726908
TI  - Increased incidence of critical illness among patients with inflammatory bowel
      disease: a population-based study.
AB  - BACKGROUND & AIMS: Little is known about how often, and for what reasons,
      patients with inflammatory bowel diseases (IBD) are admitted to the intensive
      care unit (ICU). We compared incidences of ICU admission, characteristics of
      critical illness, and mortality after ICU admission between patients with IBD and
      the general population. METHODS: We identified all persons with IBD in the
      province of Manitoba using a validated administrative definition of IBD for the
      period from 1984 to 2010. Cases were considered incident for IBD if their first
      health system contact for IBD was in 1989 or later. We identified a population
      based control group, matched by age, sex, and geography (based on postal code).
      Case and control cohorts were linked to the Manitoba ICU database. We compared
      outcomes between groups using age- and sex-standardized rates, Cox proportional
      hazards models, and logistic regression models, adjusting for age, sex,
      comorbidity, and socioeconomic status. RESULTS: There were 8224 prevalent and
      4580 incident cases of IBD. After adjustment, the risk for ICU admission was
      higher for patients with IBD than controls (hazard ratio [HR], 1.79; 95%
      confidence interval [CI], 1.58-2.02). The risk of ICU admission was higher for
      patients with Crohn's disease (HR, 2.31; 95% CI, 1.95-2.75) than ulcerative
      colitis (HR, 1.37; 95% CI, 1.13-1.65). From 2000 through 2010, age- and sex
      standardized annual incidence rates for ICU admission in the prevalent IBD cohort
      ranged from 0.55% to 1.12%. Compared with controls admitted to ICUs, 1 year after
      ICU admission, mortality was 32% among patients with IBD. CONCLUSIONS: Patients
      with IBD have a higher risk for admission to the ICU than the general population,
      and increased mortality 1 year after admission. These findings underscore the
      potential severity of IBD.

PMID- 24726909
TI  - Evaluation of antibacterial photodynamic therapy effects on human dental pulp
      cell cultures.
AB  - BACKGROUND: The antibacterial photodynamic therapy (aPDT) has been used in
      dentistry against oral microorganisms because of its excellent biocide effect.
      However, for carious lesions applications, there is little evidence that this
      therapy is safe for the pulp tissue. OBJECTIVE: This study evaluates the effects
      of an aPDT protocol on human pulp cells in vitro. METHODS: Pulp cells isolated
      from dental pulp were exposed to an aPDT protocol associating methylene blue (MB)
      at concentrations of 0.0125, 0.025 and 0.050mg/ml and red laser irradiation using
      a continuous-wave indium-gallium-aluminum-phosphide (InGaAlP) diode laser
      (lambda=660nm, 40mW, 2.4J, 60J/cm(2) for 1min). Pre-irradiation time was 5min for
      each MB concentration. Cell viability was determined by MTT assay and activity of
      alkaline phosphatase was assessed by BCIP-NBT assay. Type of aPDT-induced cell
      death was assessed by flow cytometry. Data was statistically compared (ANOVA
      followed by Tukey' or Bonferroni's post hoc tests). RESULTS: aPDT was able to
      kill pulp cells in a dye concentration-dependent manner. The cellular viability
      was significantly reduced when used MB at 0.025 or 0.050mg/ml concentrations
      (p<0.0001). At these concentrations, aPDT-induced cell death occurred mostly by
      necrosis. Alkaline phosphatase activity was significantly reduced in all
      experimental groups (p<0.001). Pulp cells showed suitable viability when MB at
      0.0125mg/ml was exposed to laser irradiation. CONCLUSIONS: aPDT with MB at
      0.0125mg/ml may represent a low-risk therapy for restorative dentistry
      applications. aPDT protocol using concentrations above 0.025mg/ml of MB
      associating red laser irradiation may be harmful for dental pulp cells.

PMID- 24726910
TI  - Detecting interaural time differences and remodeling their representation.
AB  - Interaural time differences (ITDs) represent an important cue in sound
      localization and auditory scene analysis. To assess this cue the auditory system
      internally delays binaural inputs to compensate for the outer delay, before
      neurons in the brainstem detect the coincident arrival of the inputs from the two
      ears. Different origins of internal delays have been controversially discussed
      and have given rise to conflicting interpretations of the ITD representation
      ensuing from coincidence detection. Yet, recent findings indicate that ITD
      representations undergo substantial transformations or remodeling after the
      detection step. Here we treat the detection step separately from remodeling, and
      explain why a similar representation of ITD across species may exist in the
      forebrain despite differences in detection and representation in the midbrain. 

PMID- 24726911
TI  - Breaching the dykes: bringing the best out of joined up public health.

PMID- 24726912
TI  - Influence of interferon-alpha on the expression of the cancer stem cell markers
      in pancreatic carcinoma cells.
AB  - The cytokine interferon-alpha (IFNalpha) belongs to the group of type I
      interferons already used in cancer therapy. This drug possesses radio- and chemo
      sensitizing, and shows anti-angiogenic properties. Cancer stem cells (CSC) are a
      unique population of tumor cells that initiate secondary tumors, and are
      responsible for metastasis formation. Patients with pancreatic ductal
      adenocarcinoma (PDAC) have an especially poor prognosis, with 5-year survival
      rates of only ~1% and median survival of 4-6 months. PDAC is characterized by the
      presence of CSC. In this work we demonstrate for the first time that IFNalpha up
      regulates the expression of the CSC markers CD24, CD44 and CD133 in in vitro and
      in vivo models of PDAC. We showed the IFNalpha effects on the migration and
      invasion of PDAC cells, which is associated with the level of the CSC marker
      expression. In vivo, this drug inhibits tumor growth but promotes metastasis
      formation in the early stage of tumor growth. We propose that IFNalpha may
      enhance the enrichment of CSC in PDAC tumors. Additionally we also suggest that
      in combination therapy of solid tumors with IFNalpha, this drug should be given
      to patients prior to chemotherapy to achieve the CSC activation. 

PMID- 24726913
TI  - Cytoplasmic domain of NCAM140 interacts with ubiquitin-fold modifier-conjugating
      enzyme-1 (Ufc1).
AB  - The neural cell adhesion molecule NCAM is implicated in different
      neurodevelopmental processes and in synaptic plasticity in adult brain. The
      cytoplasmic domain of NCAM interacts with several cytoskeletal proteins and
      signaling molecules. To identify novel interaction partners of the cytosolic
      domain of NCAM a protein macroarray has been performed. We identified the
      ubiquitin-fold modifier-conjugating enzyme-1 (Ufc1) as an interaction partner of
      NCAM140. Ufc1 is one of the enzymes involved in modification of proteins with the
      ubiquitin-like molecule ubiquitin-fold modifier-1 (Ufm1). We also observed a
      partial co-localization of NCAM140 with Ufc1 and Ufm1 and increased endocytosis
      of NCAM140 in the presence of Ufm1 suggesting a possible ufmylation of NCAM140
      and a potential novel function of Ufm1 for cell surface proteins. 

PMID- 24726914
TI  - SULF1/SULF2 splice variants differentially regulate pancreatic tumour growth
      progression.
AB  - This study highlights the highly dynamic nature of SULF1/SULF2 splice variants in
      different human pancreatic cancers that regulate the activities of multiple cell
      signalling pathways in development and disease. Most pancreatic tumours expressed
      variable levels of both SULF1 and SULF2 variants including some expression during
      inflammation and pancreatitis. Many ductal and centro-acinar cell-derived
      pancreatic tumours are known to evolve into lethal pancreatic ductal
      adenocarcinomas but the present study also detected different stages of such
      tumour progression in the same tissue biopsies of not only acinar cell origin but
      also islet cell-derived cancers. The examination of caerulein-induced pancreatic
      injury and tumorigenesis in a Kras-driven mouse model confirmed the activation
      and gradual increase of SULF1/SULF2 variants during pancreatitis and
      tumorigenesis but with reduced levels in Stat3 conditional knockout mice with
      reduced inflammation. The significance of differential spatial and temporal
      patterns of specific SULF1/SULF2 splice variant expression during cancer growth
      became further apparent from their differential stimulatory or inhibitory effects
      on growth factor activities, tumour growth and angiogenesis not only during in
      vitro but also in vivo growth thus providing possible novel therapeutic targets. 

PMID- 24726915
TI  - ANKHD1, a novel component of the Hippo signaling pathway, promotes YAP1
      activation and cell cycle progression in prostate cancer cells.
AB  - ANKHD1 is a multiple ankyrin repeat containing protein, recently identified as a
      novel member of the Hippo signaling pathway. The present study aimed to
      investigate the role of ANKHD1 in DU145 and LNCaP prostate cancer cells. ANKHD1
      and YAP1 were found to be highly expressed in prostate cancer cells, and ANKHD1
      silencing decreased cell growth, delayed cell cycle progression at the S phase,
      and reduced tumor xenograft growth. Moreover, ANKHD1 knockdown downregulated YAP1
      expression and activation, and reduced the expression of CCNA2, a YAP1 target
      gene. These findings indicate that ANKHD1 is a positive regulator of YAP1 and
      promotes cell growth and cell cycle progression through Cyclin A upregulation. 

PMID- 24726916
TI  - Carcinoembryonic antigen promotes colorectal cancer progression by targeting
      adherens junction complexes.
AB  - Oncomarkers play important roles in the detection and management of human
      malignancies. Carcinoembryonic antigen (CEA, CEACAM5) and epithelial cadherin (E
      cadherin) are considered as independent tumor markers in monitoring metastatic
      colorectal cancer. They are both expressed by cancer cells and can be detected in
      the blood serum. We investigated the effect of CEA production by MIP101
      colorectal carcinoma cell lines on E-cadherin adherens junction (AJ) protein
      complexes. No direct interaction between E-cadherin and CEA was detected;
      however, the functional relationships between E-cadherin and its AJ partners:
      alpha-, beta- and p120 catenins were impaired. We discovered a novel interaction
      between CEA and beta-catenin protein in the CEA producing cells. It is shown in
      the current study that CEA overexpression alters the splicing of p120 catenin and
      triggers the release of soluble E-cadherin. The influence of CEA production by
      colorectal cancer cells on the function of E-cadherin junction complexes may
      explain the link between the elevated levels of CEA and the increase in soluble E
      cadherin during the progression of colorectal cancer. 

PMID- 24726917
TI  - Role of PFC during retrieval of recognition memory in rodents.
AB  - One of the challenges for memory researches is the study of the neurobiology of
      episodic memory which is defined by the integration of all the different
      components of experiences that support the conscious recollection of events. The
      features of episodic memory includes a particular object or person ("what"), the
      context in which the experience took place ("where") and the particular time at
      which the event occurred ("when"). Although episodic memory has been mainly
      studied in humans, there are many studies that demonstrate these features in non
      human animals. Here, we summarize a set of studies that employ different versions
      of recognition memory tasks in animals to study the role of the medial prefrontal
      cortex in episodic memory. 

PMID- 24726918
TI  - A mutation in the catalytic loop of Hsp90 specifically impairs ATPase stimulation
      by Aha1p, but not Hch1p.
AB  - Heat shock protein 90 (Hsp90) is a molecular chaperone that plays a central role
      in maintaining cellular homeostasis by facilitating activation of a large number
      of client proteins. ATP-dependent client activation by Hsp90 is tightly regulated
      by a host of co-chaperone proteins that control progression through the
      activation cycle. ATPase stimulation of Hsp90 by Aha1p requires a conserved RKxK
      motif that interacts with the catalytic loop of Hsp90. In this study, we explore
      the role of this RKxK motif in the biological and biochemical properties of
      Hch1p. We found that this motif is required for Hch1p-mediated ATPase stimulation
      in vitro, but mutations that block stimulation do not impair the action of Hch1p
      in vivo. This suggests that the biological function of Hch1p is not directly
      linked to ATPase stimulation. Moreover, a mutation in the catalytic loop of Hsp90
      specifically impairs ATPase stimulation by Aha1p but not by Hch1p. Our work here
      suggests that both Hch1p and Aha1p regulate Hsp90 function through interaction
      with the catalytic loop but do so in different ways. 

PMID- 24726919
TI  - Elucidating the mechanism of substrate recognition by the bacterial Hsp90
      molecular chaperone.
AB  - Hsp90 is a conformationally dynamic molecular chaperone known to promote the
      folding and activation of a broad array of protein substrates ("clients"). Hsp90
      is believed to preferentially interact with partially folded substrates, and it
      has been hypothesized that the chaperone can significantly alter substrate
      structure as a mechanism to alter the substrate functional state. However,
      critically testing the mechanism of substrate recognition and remodeling by Hsp90
      has been challenging. Using a partially folded protein as a model system, we find
      that the bacterial Hsp90 adapts its conformation to the substrate, forming a
      binding site that spans the middle and C-terminal domains of the chaperone. Cross
      linking and NMR measurements indicate that Hsp90 binds to a large partially
      folded region of the substrate and significantly alters both its local and long
      range structure. These findings implicate Hsp90's conformational dynamics in its
      ability to bind and remodel partially folded proteins. Moreover, native-state
      hydrogen exchange indicates that Hsp90 can also interact with partially folded
      states only transiently populated from within a thermodynamically stable, native
      state ensemble. These results suggest a general mechanism by which Hsp90 can
      recognize and remodel native proteins by binding and remodeling partially folded
      states that are transiently sampled from within the native ensemble. 

PMID- 24726921
TI  - Effect of amniotic fluid on the in vitro culture of human corneal endothelial
      cells.
AB  - The present study was designed to evaluate the effects of human amniotic fluid
      (HAF) on the growth of human corneal endothelial cells (HCECs) and to establish
      an in vitro method for expanding HCECs. HCECs were cultured in DMEM-F12
      supplemented with 20% fetal bovine serum (FBS). Confluent monolayer cultures were
      trypsinized and passaged using either FBS- or HAF-containing media. Cell
      proliferation and cell death ELISA assays were performed to determine the effect
      of HAF on cell growth and viability. The identity of the cells cultured in 20%
      HAF was determined using immunocytochemistry (ICC) and real-time reverse
      transcription polymerase chain reaction (RT-PCR) techniques to evaluate the
      expression of factors that are characteristic of HCECs, including Ki-67,
      Vimentin, Na+/K+-ATPase and ZO-1. HCEC primary cultures were successfully
      established using 20% HAF-containing medium, and these cultures demonstrated
      rapid cell proliferation according to the cell proliferation and death ELISA
      assay results. The ICC and real time RT-PCR results indicated that there was a
      higher expression of Na+/K+-ATPase and ZO-1 in the 20% HAF cell cultures compared
      with the control (20% FBS) (P < 0.05). The 20% HAF-containing medium exhibited a
      greater stimulatory effect on HCEC growth and could represent a potential
      enriched supplement for HCEC regeneration studies. 

PMID- 24726920
TI  - All-trans-retinal induces Bax activation via DNA damage to mediate retinal cell
      apoptosis.
AB  - The current study investigates the cellular events which trigger activation of
      proapoptotic Bcl-2-associated * protein (Bax) in retinal cell death induced by
      all-trans-retinal (atRAL). Cellular events which activate Bax, such as DNA damage
      by oxidative stress and phosphorylation of p53, were evaluated by immunochemical
      and biochemical methods using ARPE-19 cells, 661 W cells, cultured neural retinas
      and a retinal degeneration model, Abca4(-/-)Rdh8(-/-) mice. atRAL-induced Bax
      activation in cultured neural retinas was examined by pharmacological and genetic
      methods. Other Bax-related cellular events were also evaluated by pharmacological
      and biochemical methods. Production of 8-OHdG, a DNA damage indicator, and the
      phosphorylation of p53 at Ser46 were detected prior to Bax activation in ARPE-19
      cells incubated with atRAL. Light exposure to Abca4(-/-)Rdh8(-/-) mice also
      caused the above mentioned events in conditions of short term intense light
      exposure and regular room lighting conditions. Incubation with Bax inhibiting
      peptide and deletion of the Bax gene partially protected retinal cells from atRAL
      toxicity in cultured neural retina. Necrosis was demonstrated not to be the main
      pathway in atRAL mediated cell death. Bcl-2-interacting mediator and Bcl-2
      expression levels were not altered by atRAL in vitro. atRAL-induced oxidative
      stress results in DNA damage leading to the activation of Bax by phosphorylated
      p53. This cascade is closely associated with an apoptotic cell death mechanism
      rather than necrosis.

PMID- 24726922
TI  - Decoding grasp force profile from electrocorticography signals in non-human
      primate sensorimotor cortex.
AB  - The relatively low invasiveness of electrocorticography (ECoG) has made it a
      promising candidate for the development of practical, high-performance neural
      prosthetics. Recent ECoG-based studies have shown success in decoding hand and
      finger movements and muscle activity in reaching and grasping tasks. However,
      decoding of force profiles is still lacking. Here, we demonstrate that lateral
      grasp force profile can be decoded using a sparse linear regression from 15 and
      16 channel ECoG signals recorded from sensorimotor cortex in two non-human
      primates. The best average correlation coefficients of prediction after 10-fold
      cross validation were 0.82+/-0.09 and 0.79+/-0.15 for our monkeys A and B,
      respectively. These results show that grasp force profile was successfully
      decoded from ECoG signals in reaching and grasping tasks and may potentially
      contribute to the development of more natural control methods for grasping in
      neural prosthetics. 

PMID- 24726923
TI  - Tryptase-PAR2 axis in experimental autoimmune prostatitis, a model for chronic
      pelvic pain syndrome.
AB  - Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) affects up to 15% of
      the male population and is characterized by pelvic pain. Mast cells are
      implicated in the murine experimental autoimmune prostatitis (EAP) model as key
      to chronic pelvic pain development. The mast cell mediator tryptase-beta and its
      cognate receptor protease-activated receptor 2 (PAR2) are involved in mediating
      pain in other visceral disease models. Prostatic secretions and urines from
      CP/CPPS patients were examined for the presence of mast cell degranulation
      products. Tryptase-beta and PAR2 expression were examined in murine EAP. Pelvic
      pain and inflammation were assessed in the presence or absence of PAR2 expression
      and upon PAR2 neutralization. Tryptase-beta and carboxypeptidase A3 were elevated
      in CP/CPPS compared to healthy volunteers. Tryptase-beta was capable of inducing
      pelvic pain and was increased in EAP along with its receptor PAR2. PAR2 was
      required for the development of chronic pelvic pain in EAP. PAR2 signaling in
      dorsal root ganglia led to extracellular signal-regulated kinase (ERK)1/2
      phosphorylation and calcium influx. PAR2 neutralization using antibodies
      attenuated chronic pelvic pain in EAP. The tryptase-PAR2 axis is an important
      mediator of pelvic pain in EAP and may play a role in the pathogenesis of
      CP/CPPS. 

PMID- 24726924
TI  - Cost-effectiveness of different strategies to manage patients with sciatica.
AB  - The aim of this paper is to estimate the relative cost-effectiveness of treatment
      regimens for managing patients with sciatica. A deterministic model structure was
      constructed based on information from the findings from a systematic review of
      clinical effectiveness and cost-effectiveness, published sources of unit costs,
      and expert opinion. The assumption was that patients presenting with sciatica
      would be managed through one of 3 pathways (primary care, stepped approach,
      immediate referral to surgery). Results were expressed as incremental cost per
      patient with symptoms successfully resolved. Analysis also included incremental
      cost per utility gained over a 12-month period. One-way sensitivity analyses were
      used to address uncertainty. The model demonstrated that none of the strategies
      resulted in 100% success. For initial treatments, the most successful regime in
      the first pathway was nonopioids, with a probability of success of 0.613. In the
      second pathway, the most successful strategy was nonopioids, followed by
      biological agents, followed by epidural/nerve block and disk surgery, with a
      probability of success of 0.996. Pathway 3 (immediate surgery) was not cost
      effective. Sensitivity analyses identified that the use of the highest cost
      estimates results in a similar overall picture. While the estimates of cost per
      quality-adjusted life year are higher, the economic model demonstrated that
      stepped approaches based on initial treatment with nonopioids are likely to
      represent the most cost-effective regimens for the treatment of sciatica.
      However, development of alternative economic modelling approaches is required. 

PMID- 24726925
TI  - RReACT goes global: perils and pitfalls of constructing a global open-access
      database of registered analgesic clinical trials and trial results.
AB  - Eliminating publication bias requires ensuring public awareness of studies and
      access to results. Clinical trial registries provide basic trial information, but
      access to unbiased trial results is inadequate. Nearly all studies of trial
      registration and results reporting have been limited to the ClinicalTrials.gov
      registry. We analyzed trial registration, registry functionality, cross-registry
      harmonization, and results reporting on all 15 primary registries in the World
      Health Organization International Clinical Trials Registry Platform (ICTRP) for
      postherpetic neuralgia, painful diabetic neuropathy, and fibromyalgia. A total of
      447 unique trials were identified, with 86 trials listed on more than one
      registry. A comprehensive search algorithm was used to find trial results in the
      peer-reviewed literature and the grey literature. Creating a global database of
      registered trials and trial results proved surprisingly difficult for several
      reasons: (1) ICTRP does not reliably identify trials listed on multiple
      registries, manual searches are necessary; (2) Searching ICTRP yields different
      results than searching individual registries; (3) Outcome measure descriptions
      for multiply registered trials vary between registries; (4) Registry-publication
      pairings are often inaccurate or incomplete; (5) Grey literature results are not
      permanent. Overall, only 46% of all trials had results available. Trials
      registered on ClinicalTrials.gov were significantly more likely to have results
      (52% vs. 18%, P<0.001), partly due to the ability to post results directly to the
      registry. In addition to the simple remedy of including trial registration
      numbers on all meeting abstracts and peer-reviewed papers, specific strategies
      are offered to facilitate identifying multiply registered studies and ensuring
      accurate pairing of results and publications.

PMID- 24726926
TI  - Prevalence of type III secretion system in effective biocontrol pseudomonads.
AB  - Functional type III secretion system (T3SS) genes are needed for effective
      biocontrol of Pythium damping-off of cucumber by Pseudomonas fluorescens KD, but
      whether biocontrol Pseudomonas strains with T3SS genes display overall a higher
      plant-protecting activity is unknown. The assessment of 198 biocontrol
      fluorescent pseudomonads originating from 60 soils worldwide indicated that 32%
      harbour the ATPase-encoding T3SS gene hrcN, which was most often found in tomato
      isolates. The hrcN(+) biocontrol strains (and especially those also producing 2,4
      diacetylphloroglucinol and displaying 1-aminocyclopropane-1-carboxylate deaminase
      activity) displayed higher plant-protecting ability in comparison with hrcN(-)
      biocontrol strains, both in the Pythium/cucumber and Fusarium/cucumber
      pathosystems.

PMID- 24726927
TI  - Preface to special issue on protein trafficking and secretion in bacteria.

PMID- 24726928
TI  - Neurotoxic evaluation of two organobromine model compounds and natural AOBr
      containing surface water samples by a Caenorhabditis elegans test.
AB  - Brominated organic compounds are known as disinfection byproducts. Very recently,
      however, even natural brominated organic compounds (analyzed as adsorbable
      organic bromine; AOBr) have been found in decaying freshwater cyanobacteria
      blooms. Among the identified compounds was dibromoacetic acid (DBAA), which has
      proven to be neurotoxic at rather high concentrations in mammalian assays.
      Currently it is open how single compounds as well as complex mixtures impact
      organisms at environmentally realistic concentrations. Furthermore, it is also
      unclear how natural organic matter, mainly humic substances (HS), which are
      present in all freshwater systems, modulates the toxic impact of AOBr. Therefore,
      two AOBr compounds (DBAA and tetrabromobisphenol-A; TBBP-A) and AOBr-containing
      water samples were tested using a Caenorhabditis elegans neurotoxicity assay that
      measured autonomic and sensory functions. TBBP-A had an impact on three response
      variables of C. elegans and can be classified neurotoxic. In contrast to our
      expectations, DBAA led to neurostimulation of two autonomic functions, but had a
      temporary impact on the defecation interval. All surface water samples contained
      measurable amounts of AOBr. Exposure of C. elegans to concentrated water samples 
      one in particular - increased three of the four locomotion traits and left
      defecation activity and both sensory variables unchanged. This stimulation might
      be due to unidentified compounds in the samples or to a hormetic effect of the
      AOBr compounds. Thermotactic behavior was characterized by a temporary preference
      for the colder environment, indicating a temporary mild neurotoxicity. Overall,
      the set of relative simple phenotypic tests used in the current study revealed a
      meaningful neurotoxic or neurostimulative profile in response to chemical
      compounds or natural samples. Furthermore, it shows that the resulting response
      to natural AOBr compounds at environmentally realistic concentrations was not
      necessarily adverse, but instead, that the mixtures of natural AOBr were
      neurostimulatory. 

PMID- 24726930
TI  - Acute effects of cadmium and copper on survival, oxygen consumption, ammonia-N
      excretion, and metal accumulation in juvenile Exopalaemon carinicauda.
AB  - Ridgetail white prawn (Exopalaemon carinicauda), a commercially important species
      in China, is a potential candidate for evaluating impairments caused by
      environmental pollutants in coastal and estuarine areas. The main purpose of the
      present study was to investigate the acute effects of cadmium (Cd) and copper
      (Cu) on survival, oxygen consumption, ammonia-N excretion, and metal accumulation
      in E. carinicauda. The feasibility of using this species for pollution monitoring
      was also evaluated. Results showed that the median lethal concentrations (LC50)
      for 24h, 48h, 72h, and 96h were 0.66mg/L, 0.379mg/L, 0.343mg/L, and 0.258mg/L for
      Cd, and 0.932mg/L, 0.748mg/L, 0.725mg/L, and 0.712mg/L for Cu. Cd exposure
      (0.66mg/L) caused an inhibition in oxygen consumption of 21.1 percent and an
      increase in ammonia-N excretion of 47.1 percent, thereby decreasing the atomic
      ratio of oxygen consumed to nitrogen consumed (O:N ratio) of 46.32 percent
      relative to the control. Cu exposure (0.932mg/L) also resulted in an inhibition
      in oxygen consumption of 34.8 percent and a decrease in the O:N ratio of 23.9
      percent in relation to the control, but the ammonia-N excretion was not
      influenced by the Cu exposure. Concentration-depended accumulation was observed
      in the experimental animals, which a maximum of 244.8 folds and 1.1 folds
      increase of mental concentration was measured upon exposure to 24h LC50 of Cd and
      Cu for 24h, respectively. The change in O:N ratio indicated an alteration in
      energy utilization. Based on its sensitivity to heavy metals and its availability
      all year round, E. carinicauda can be used as a test organism to monitor for
      metal pollution. 

PMID- 24726929
TI  - Exogenous jasmonic acid can enhance tolerance of wheat seedlings to salt stress.
AB  - Jasmonic acid (JA) is regarded as endogenous regulator that plays an important
      role in regulating stress responses, plant growth and development. To investigate
      the physiological mechanisms of salt stress mitigated by exogenous JA, foliar
      application of 2mM JA was done to wheat seedlings for 3days and then they were
      subjected to 150mM NaCl. Our results showed that 150mM NaCl treatment
      significantly decreased plant height, root length, shoot dry weight, root dry
      weight, the concentration of glutathione (GSH), chlorophyll b (Chl b) and
      carotenoid (Car), the activities of superoxide dismutase (SOD), peroxidase (POD),
      catalase (CAT), ascorbate peroxidase (APX), enhanced the concentration of
      malondialdehyde (MDA), hydrogen peroxide (H2O2) and the rate of superoxide
      radical (O2*-) generation in the wheat seedlings when compared with the control.
      However, treatments with exogenous JA for 3 days significantly enhanced salt
      stress tolerance in wheat seedlings by decreasing the concentration of MDA and
      H2O2, the production rate of O2*- and increasing the transcript levels and
      activities of SOD, POD, CAT and APX and the contents of GSH, Chl b and Car,
      which, in turn, enhanced the growth of salt stressed seedlings. These results
      suggested that JA could effectively protect wheat seedlings from salt stress
      damage by enhancing activities of antioxidant enzymes and the concentration of
      antioxidative compounds to quench the excessive reactive oxygen species caused by
      salt stress and presented a practical implication for wheat cultivation in salt
      affected soils.

PMID- 24726931
TI  - Determination of 33 elements in scalp hair samples from inhabitants of a mountain
      village of Tonglu city, China.
AB  - Hair samples from 190 relatively healthy 20- to 98-year-old volunteers from a
      mountain village of Tonglu city (Zhejiang province, China) were analyzed to
      determine the contents of 33 chemical elements (Ag, Al, As, Au, B, Ba, Be, Ca,
      Cd, Co, Cr, Cs, Cu, Fe, Ga, Hg, Li, Mg, Mn, Mo, Ni, Pb, Rb, Sb, Se, Sr, Th, Ti,
      Tl, U, V, Zn, and Zr) with the aim of assessing preliminary reference values.
      Mean values, median values, ranges and selected percentiles of all element
      concentrations in scalp hair are presented. By comparing data from different
      countries, it was determined that the mean concentrations of the majority of
      elements in our study clearly differed from the mean levels reported in the
      literature. The effects of gender and age on element concentrations were also
      investigated. Significant differences that were correlated with age and gender
      were determined for certain elements. For example, Fe exhibited a mean value of
      11.26mg/kg for males and 4.37mg/kg for females. An age-dependent pattern for Fe
      was also apparent when the two age subgroups of 20-59 and 60-98 years were
      compared. 

PMID- 24726932
TI  - Concurrent degradation of tetrabromobisphenol A by Ochrobactrum sp. T under
      aerobic condition and estrogenic transition during these processes.
AB  - The effect of concurrent degradation of tetrabromobisphenol A (TBBPA) by the
      strain Ochrobactrum sp. T under aerobic condition was investigated. The results
      demonstrated that four extra energy source-addition systems still followed pseudo
      first order kinetics. The addition of ethanol or glucose could promote the
      biodegradation ability of Ochrobactrum sp. T to TBBPA, and 90.1 percent and 77.5
      percent of TBBPA (5mg L(-1)) could be removed with corresponding TBBPA half-lives
      of 26 and 36h, respectively, after 96h reaction. Comparatively, the degradation
      efficiency of the sole TBBPA system was only 72.9 percent under the same
      condition. In contrast, two other co-substrates 2,4,6-tribromophenol (TBP) and
      bisphenol A (BPA) showed a negative effect on the TBBPA biodegradation, and the
      degradation efficiencies of TBBPA were achieved as 44.7 percent and 67.4 percent,
      respectively. For the TBBPA+TBP system, the competitive inhibition for the TBBPA
      debromination was less than the inhibition of the toxicity to the bacterium.
      While for the TBBPA+BPA system, the degradation of TBBPA could be promoted at the
      beginning of the reaction, and was then inhibited slightly with further
      prolonging of reaction time. This is probably due to the substrates being
      oxidized, and BPA can consume partial oxygen and provide the electrons during the
      concurrent biodegradation process. In addition, although higher estrogenic
      activity could be detected for the debrominated intermediates in TBBPA co
      degradation process than the original TBBPA, the estrogenicity of the whole
      system still decreased finally after 96h degradation.

PMID- 24726933
TI  - Development of a biopolymer nanoparticle-based method of oral toxicity testing in
      aquatic invertebrates.
AB  - Aquatic toxicity testing generally focuses on the water absorption/dermal route
      of exposure to potential toxic chemicals, while much less work has been done on
      the oral route of exposure. This is due in part to the difficulties of applying
      traditional oral toxicity testing to aquatic environments, including the tendency
      for test chemicals to dissolve into water. The use of biopolymer nanoparticles to
      encapsulate test chemicals onto food to prevent dissolution is one solution
      presented herein. The biopolymers zein and chitosan were explored for their
      previously known nanoparticle-forming abilities. Nanoparticles containing the
      test chemical rhodamine B were formed, applied as films to coat food, and then
      fed to the test organism, the freshwater amphipod Hyalella azteca. In feeding
      trials both zein and chitosan nanoparticles showed a significantly lower release
      rate of rhodamine B into water than food dyed with rhodamine B without biopolymer
      nanoparticles. Zein nanoparticles also showed better retention ability than
      chitosan nanoparticles. Both kinds of nanoparticles showed no significant effect
      on the survival, growth, or feeding behavior of H. azteca. Thus these biopolymers
      may be an effective system to encapsulate and deliver chemicals to aquatic
      invertebrates without interfering with common toxicity assessment endpoints like
      survival and growth. 

PMID- 24726934
TI  - Effect of water quality on mercury toxicity to Photobacterium phosphoreum: Model
      development and its application in natural waters.
AB  - Mercury (Hg) compounds are widely distributed toxic environmental and industrial
      pollutants and they may bring danger to growth and development of aquatic
      organisms. The distribution of Hg species in the 3 percent NaCl solution was
      calculated using the chemical equilibrium model Visual MINTEQ, which demonstrated
      that Hg was mainly complexed by chlorides in the pH range 5.0-9.0 and the
      proportions of HgCl4(2-), HgCl3(-) and HgCl2(aq) reached to 95 percent of total
      Hg. Then the effects of cations (Ca(2+), Mg(2+), K(+) and H(+)), anions (HCO3(-),
      NO3(-), SO4(2-) and HPO4(2-)) and complexing agents (ethylene diamine tetraacetic
      acid (EDTA) and dissolved organic matter (DOM)) on Hg toxicity to Photobacterium
      phosphoreum were evaluated in standardized 15min acute toxicity tests. The
      significant increase of 6.3-fold in EC50 data with increasing pH was observed
      over the tested pH range of 5.0-8.0, which suggested the possible competition
      between hydroxyl and the negatively charged chloro-complex. By contrast, it was
      found that major cations (Ca(2+), Mg(2+) and K(+)) have little effect on Hg
      toxicity to P. phosphoreum. An interesting finding was that the addition of
      HPO4(2-) significantly increased Hg toxicity, which may imply that the addition
      of phosphate increased the soluble Hg-chloro complex species. Additions of
      complexing agents (EDTA and DOM) into the exposure water increased Hg
      bioavailability via complexation of Hg. Finally, a model which incorporated the
      effect of pH, HPO4(2-), HCO3(-), SO4(2-) and DOM on Hg toxicity was developed to
      predict acute Hg toxicity for P. phosphoreum, which may be a useful tool in
      setting realistic water quality criteria for different types of water. 

PMID- 24726935
TI  - Novel approach to ecotoxicological risk assessment of sediments cores around the
      shipwreck by the use of self-organizing maps.
AB  - Marine and coastal pollution plays an increasingly important role due to recent
      severe accidents which drew attention to the consequences of oil spills causing
      widespread devastation of marine ecosystems. All these problems cannot be solved
      without conducting environmental studies in the area of possible oil spill and
      performing chemometric evaluation of the data obtained looking for similar
      patterns among pollutants and optimize environmental monitoring during eventual
      spills and possible remediation actions - what is the aim of the work presented.
      Following the chemical and ecotoxicological studies self-organising maps
      technique has been applied as a competitive learning algorithm based on
      unsupervised learning process. Summarizing it can be stated that biotests enable
      assessing the impact of complex chemical mixtures on the organisms inhabiting
      particular ecosystems. Short and simple application of biotests cannot easily
      explain the observable toxicity without more complex chemometric evaluation of
      datasets obtained describing dependence between xenobiotics and toxicological
      results. 

PMID- 24726936
TI  - Ecotoxicological evaluation of selected pharmaceuticals to Vibrio fischeri and
      Daphnia magna before and after photooxidation process.
AB  - The aim of the research was the determination of the toxicity of
      photocatalytically treated water contaminated by different pharmaceuticals:
      chloramphenicol (CPL), diclofenac (DCF) or metoprolol (MT). Daphtoxkit FTM with
      Dapnia magna and Microtox((r)) with Vibrio fischeri were used to evaluate the
      toxicity of the water before and after treatment. D. magna showed higher
      sensitivity to the presence of pharmaceuticals than V. fischeri. Generally, both
      tested organisms revealed the greatest sensitivity to the presence of CPL. The
      application of photocatalytic oxidation has resulted in decreased toxicity. It
      may confirm the reduction of high toxic parent compounds to less toxic
      metabolites. The toxicity was reduced in the range from 30% to 100% depending on
      pharmaceutical tested. The highest reduction of toxicity to V. fischeri and D.
      magna was observed to MT and CPL respectively. Depending on bioassay the toxicity
      decrease as follows: CPL>DCF>MT for D. magna and CPL>MT>DCF for V. fischeri.

PMID- 24726937
TI  - Preparation of Enteromorpha prolifera-based cetyl trimethyl ammonium bromide
      doped activated carbon and its application for nickel(II) removal.
AB  - Activated carbon was prepared from Enteromorpha prolifera (EP) by H3PO4
      activation in the presence of doped cetyl trimethyl ammonium bromide (CTAB),
      producing EPAC-CTAB. The thermal decomposition process of the activated carbon
      substrate was identified by thermo-gravimetric analysis. Scanning electron
      microscope (SEM), N2 adsorption/desorption, Fourier transform infrared
      spectroscopy (FTIR), Boehm titration, and X-ray Photoelectron Spectroscopy (XPS)
      were employed to characterize the physicochemical properties of native EPAC and
      EPAC-CTAB. EPAC-CTAB exhibited smaller surface area (689.0m(2)/g) and lower total
      pore volume (0.361cm(3)/g) than those of EPAC (1045.8m(2)/g and 1.048cm(3)/g),
      while the number of acidic groups, oxygen and nitrogen groups on the surface of
      EPAC-CTAB increased through CTAB doping. The batch kinetics and isotherm
      adsorption studies of nickel(II) onto the adsorbents were examined and agreed
      well with the pseudo-second-order model and the Langmuir model. The maximum
      adsorption capacity determined from the Langmuir model was 16.9mg/g for EPAC and
      49.8mg/g for EPAC-CTAB. Under acidic condition, the adsorption of nickel(II) onto
      EPAC and EPAC-CTAB was hindered due to ion competition and electrostatic
      repulsion. The results indicated that using CTAB as a dopant for EPAC
      modification could markedly enhance the nickel(II) removal. 

PMID- 24726938
TI  - Cholinesterase activity in the caddisfly Sericostoma vittatum: Biochemical enzyme
      characterization and in vitro effects of insecticides and psychiatric drugs.
AB  - Sericostoma vittatum is a caddisfly species, endemic to the Iberian Peninsula,
      proposed as a biomonitor species for lotic ecosystems. Since inhibition of
      cholinesterases' (ChE) activity has been used to evaluate the exposure of
      macroinvertebrates to organophosphates and carbamate pesticides, this work
      intended to characterize the ChE present in this species so their activity can be
      used as a potential biomarker of exposure. Biochemical and pharmacological
      properties of ChE were characterized in this caddisfly species using different
      substrates (acetylthiocholine iodide, propionylthiocholine iodide, and
      butyrylthiocholine iodide) and selective inhibitors (eserine sulfate, BW284c51,
      and iso-OMPA). Also, the in vitro effects of two insecticides (carbaryl and
      chlorantraniliprole) and two psychiatric drugs (fluoxetine and carbamazepine) on
      ChE activity were investigated. The results suggest that S. vittatum possess
      mainly AChE able to hydrolyze both substrates acetylthiocholine and
      propionylthiocholine since: (1) it hydrolyzes the substrate acetylthiocholine and
      propionylcholine at similar rates and butyrylthiocholine at a much lower rate;
      (2) it is highly sensitive to eserine sulfate and BW284c51, but not to iso-OMPA;
      and (3) its activity is inhibited by excess of substrate, a characteristic of
      typical AChE. in vitro inhibitions were observed only for carbaryl exposure while
      exposure to chlorantraniliprole and to relevant environmental concentrations of
      psychiatric drugs did not cause any significant effect on AChE activity. This
      study suggests that AChE activity in caddisflies can indeed be used to
      discriminate the effects of specific insecticides in monitoring programs. The use
      of non-target species such as caddisflies in ecotoxicological research in lotic
      ecosystems is also discussed. 

PMID- 24726939
TI  - Developmental toxicity in rare minnow (Gobiocypris rarus) embryos exposed to Cu,
      Zn and Cd.
AB  - Using rare minnow (Gobiocypris rarus) embryos as experimental model, the
      developmental toxicity of Cu, Zn and Cd were investigated following exposure to
      0.001-1.000mg/L for 72h, and the toxicity effects were evaluated by larval
      malformation rate, heart rate, pericardial area, spontaneous movements, tail
      length, enzyme activities and biomarker genes. Our results revealed that
      increased malformation rate provide a gradual dose-response relationship, and the
      most pronounced morphological alteration was heart and body malformations. Values
      of 72h EC50 with their 95 percent confidence intervals on G. rarus embryos were
      0.103 (0.072-0.149)mg/L for Cu, 0.531 (0.330-1.060)mg/L for Zn, 0.219 (0.147
      0.351)mg/L for Cd. Enzyme activities can be regard as a type of low-dose
      stimulation and high-dose inhibition. Stress and metabolism-related genes (hsp70,
      cyp1a and mt) were significantly up-regulated, development-related genes (wnt8a,
      vezf1 and mstn) were significantly down-regulated after the treatment by Cu, Zn
      and Cd. Overall, the present study points out Cu, Zn and Cd are highly toxic to
      G. rarus embryos. The information presented in this study will be helpful in
      fully understanding the toxicity induced by Cu, Zn and Cd in fish embryos. 

PMID- 24726940
TI  - Physiological responses of biomass allocation, root architecture, and invertase
      activity to copper stress in young seedlings from two populations of Kummerowia
      stipulacea (maxim.) Makino.
AB  - In the current study, we hypothesize that mine (metallicolous) populations of
      metallophytes form a trade-off between the roots and shoots when under copper
      (Cu) stress to adapt themselves to heavy metal contaminated habitats, and thus,
      differ from normal (non-metallicolous) populations in biomass allocation. To test
      the hypothesis, two populations of the metallophyte Kummerowia stipulacea, one
      from an ancient Cu mine (MP) and the other from a non-contaminated site (NMP),
      were treated with Cu(2+) in hydroponic conditions. The results showed that MP
      plants had higher root/shoot biomass allocation and more complicated root system
      architecture compared to those of the NMP plants when under Cu stress. The net
      photosynthetic capacity was more inhibited in the NMP plants than in the MP
      plants when under Cu stress. The sugar (sucrose and hexose) contents and acid
      invertase activities of MP plants were elevated while those in NMP plants were
      inhibited after Cu treatment. The neutral/alkaline invertase activities and
      sucrose synthase level showed no significant differences between the two
      populations when under Cu stress. The results showed that acid invertase played
      an important role in biomass allocation and that the physiological responses were
      beneficial for the high root/shoot biomass allocation, which were advantageous
      during adaptive evolution to Cu-enriched mine soils. 

PMID- 24726941
TI  - Influence of Pseudomonas aeruginosa as PGPR on oxidative stress tolerance in
      wheat under Zn stress.
AB  - Plant Growth Promoting Rhizobacteria (PGPR), whose role is still underestimated,
      plays an important (or perhaps essential) role in improving plant growth. The
      comprehensive understanding of bacterial plant growth promoting mechanism helps
      to get sustainable agriculture production under biotic and abiotic stresses. In
      the present study, plant growth promoting (PGP) bacterial strain Pseudomonas
      aeruginosa having maximum inhibitory concentration of 1500mg kg(-1) against Zn
      was isolated from arable land, irrigated with industrial effluent and evaluated
      to determine it bioremediation potential. The study was mainly focused on plant
      biomass production, nutrient uptake and oxidative stress tolerance in relation to
      the activities of antioxidative enzymes and the content of non-enzymatic
      antioxidants. The oxidative stress tolerance was measured by estimating the MDA
      accumulation as well as H2O2 production in wheat plants under Zn (1000mg kg(-1))
      stress and inoculation of soil with Zn resistant Pseudomonas aeruginosa. Zn in
      rooting medium reduced the plant growth, leaf photosynthetic pigments as well as
      uptake of N and P. However, content of MDA and H2O2 increased at higher
      concentration of Zn. Inoculation of P. aeruginosa improved the uptake of P and N
      in wheat plants with an increase in leaf chlorophyll, total soluble protein and
      plant biomass production. Analysis of plant root and shoot disclosed that Zn
      concentration was significantly lowered in P. aeruginosa inoculated zinc stressed
      plants as compare to the plants grown under Zn stress only. The amelioration of
      adverse effects of Zn stress on biomass production due to P. aeruginosa
      inoculation was related with enhanced antioxidative enzyme activities (SOD, POD
      and CAT), and the contents of non-enzymatic components such as ascorbic acid and
      total phenolics (TPC) as compare to Zn-treated plants. The up-gradation in
      antioxidative defense mechanism, resulted a reduction in H2O2 and MDA content due
      to the scavenging of ROS by antioxidants. It was concluded that P. aeruginosa is
      an ideal candidate for bioremediation and wheat growth promotion against Zn
      induced oxidative stress by improving the availability of necessary nutrient,
      eliciting antioxidant defense system as well as by lowering the Zn metal uptake.

PMID- 24726942
TI  - ROI-scavenging enzyme activities as toxicity biomarkers in three species of
      marine microalgae exposed to model contaminants (copper, Irgarol and atrazine).
AB  - There is a need to develop efficient tools to prevent damage to marine ecosystems
      due to pollution. Since microalgae play a key role in marine ecosystems, they are
      considered potentially useful for quick and sensitive toxicity bioassays. In this
      study an integrative analysis has been carried out of the anti-oxidant enzyme
      activities of marine microalgae species. Three marine microalgae species
      (Cylindrotheca closterium, a benthic diatom; Phaeodactylum tricornutum, a diatom
      which has been used as model organism in toxicity bioassays; and Rhodomonas
      salina, a cryptophyceae which is considered to present a certain level of
      heterotrophy) were exposed to selected concentrations of three model pollutants:
      copper (5 and 10ug L(-1)), atrazine (25 and 50ug L(-1)) and Irgarol (0.5 and
      1.0ug L(-1)). These pollutant concentrations are environmentally relevant for
      coastal ecosystems, and have been selected for checking the efficiency of the
      reactive oxygen intermediate (ROI) scavenging enzyme system of these organisms.
      Superoxide dismutase (SOD), catalase (CAT), ascorbate peroxidase (APx) and
      glutathione peroxidase (GPx) activities were measured at the end of 24h exposure.
      The integrated biomarker response (IBR) index - in our case for oxidative stress 
      has been employed to evaluate the ROI-scavenging enzyme system for each species
      and each treatment. In general, the SOD and CAT enzyme activities measured were
      higher in exposed populations than in controls, whereas APx and GPx activities
      showed the opposite trend. These microalgae showed significant responses of
      oxidative stress biomarkers at environmentally relevant concentrations for the
      assayed pollutants and short exposure periods, conditions that most other model
      organisms cannot match. Therefore microalgae present clear advantages over other
      species for their prospective employment in an "early warning system".

PMID- 24726943
TI  - Effect of silver nanoparticles on rice (Oryza sativa L. cv. KDML 105) seed
      germination and seedling growth.
AB  - With the advances in nanotechnology, silver nanoparticles (AgNPs) have been
      applied in many industries, increasing their potential exposure level in the
      environment, yet their environmental safety remains poorly evaluated. The
      possible effects of different sized AgNPs (20, 30-60, 70-120 and 150nm diameter)
      on jasmine rice, Oryza sativa L. cv. KDML 105, were investigated at different
      concentrations (0.1, 1, 10, 100 and 1000mg/L) upon seed germination and seedling
      growth. The results revealed that the level of seed germination and subsequent
      growth of those seedlings that germinated were both decreased with increasing
      sizes and concentrations of AgNPs. Based on the analysis of AgNPs accumulation in
      plant tissues, it implied that the higher uptake was found when the seeds were
      treated with the smaller AgNPs, 20nm diameter AgNPs, but it was trapped in the
      roots rather than transported to the leaves. These resulted in the less negative
      effects on seedling growth, when compared to the seed soaking with the larger
      AgNPs with 150nm diameter. The negative effects of AgNPs were supported by leaf
      cell deformation when rice seeds were treated with 150-nm-diameter AgNP at the
      concentration of 10 or 100mg/L during seed germination. These results further
      strengthen our understanding of environmental safety information with respect to
      nanomaterials. 

PMID- 24726944
TI  - Chronic effects of environmentally-relevant concentrations of lead in Pelophylax
      nigromaculata tadpoles: Threshold dose and adverse effects.
AB  - Lead (Pb) is a common heavy metal in the natural environment, but its
      concentration has been increasing alongside widespread industrial and
      agricultural development in China. The dark-spotted frog Pelophylax (formerly
      Rana) nigromaculata (Anura: Ranidae) is distributed across East Asia and inhabits
      anthropogenic habitats such as farmland. Here, P. nigromaculata tadpoles (Gosner
      stage 19-46) were exposed to Pb at different concentrations (0, 40, 80, 160, 320,
      640 and 1280ug/L) and Pb-induced survival, metamorphosis time, development,
      malformations, mobility and gonad structure were monitored. The results showed
      that above the threshold concentration of Pb, adverse effects were obvious. As
      the concentration of Pb increased, the adverse effects on different traits
      followed different patterns: the effects on hindlimb length, survival rate,
      metamorphosis rate, total malformation rate, swimming speed and jumping speed
      largely exhibited a linear pattern; the effects on snout-vent length, body mass
      and forelimb length largely exhibited a bimodal pattern. Sex ratio and gonadal
      histology were not affected by Pb, suggesting that Pb is not strongly estrogenic
      in P. nigromaculata. 

PMID- 24726945
TI  - Regulation of lead toxicity by heat shock protein 90 (daf-21) is affected by
      temperature in Caenorhabditis elegans.
AB  - In the nematode Caenorhabditis elegans, stress resistance can be regulated by
      dauer formation (daf) genes. In the present study, regulation of heavy metal lead
      (Pb) toxicity by the 90-kDa heat shock proteins (Hsp90; daf-21) was investigated
      in both wild-type C. elegans and daf-21/Hsp90 mutants by focusing on the effects
      of varied temperatures below (15 degrees C) or above (25 and 30 degrees C) the
      presumptive optimum growth temperature (20 degrees C). More acute toxicity of Pb,
      indicated by the 24-h median lethal concentrations (LC50), was observed in wild
      type adults than in the daf-21 mutant adults at 15, 20 and 25 degrees C; however,
      the daf-21 mutant adults showed more sensitivity at 30 degrees C. Enhanced Pb
      sensitivity (e.g., decrease LC50) in both types of C. elegans was observed with
      both increased and decreased temperatures when compared to that at 20 degrees C.
      Additional examined endpoints included time course of toxicity at LC50s,
      pharyngeal pumping, reproduction, life span, and Hsp90 expression. Collective
      results showed that temperatures both above and below 20 degrees C exacerbated Pb
      toxicity, and that the protein level of daf-21/Hsp90 was one of the most
      sensitive indicators of Pb toxicity in wild-type C. elegans, while pharyngeal
      pumping was more Pb sensitive in daf-21 mutants. Therefore, the expression of daf
      21/Hsp90 has apparent utility for the prediction and assessment of Pb-induced
      toxicity in nematodes. Further, the stress responses related to Hsp90 expression
      in C. elegans may have considerable potential as sensitive biomarkers for the
      monitoring of environmental Pb contamination. 

PMID- 24726946
TI  - Serum lactate as a novel potential biomarker in multiple sclerosis.
AB  - Multiple sclerosis (MS) is a primary inflammatory demyelinating disease
      associated with a probably secondary progressive neurodegenerative component.
      Impaired mitochondrial functioning has been hypothesized to drive
      neurodegeneration and to cause increased anaerobic metabolism in MS. The aim of
      our multicentre study was to determine whether MS patients had values of
      circulating lactate different from those of controls. Patients (n=613) were
      recruited, assessed for disability and clinically classified (relapsing
      remitting, secondary progressive, primary progressive) at the Catholic University
      of Rome, Italy (n=281), at the MS Centre Amsterdam, The Netherlands (n=158) and
      at the S. Camillo Forlanini Hospital, Rome, Italy (n=174). Serum lactate levels
      were quantified spectrophotometrically with the analyst being blinded to all
      clinical information. In patients with MS serum lactate was three times higher
      (3.04+/-1.26mmol/l) than that of healthy controls (1.09+/-0.25mmol/l, p<0.0001)
      and increased across clinical groups, with higher levels in cases with a
      progressive than with a relapsing-remitting disease course. In addition, there
      was a linear correlation between serum lactate levels and the expanded disability
      scale (EDSS) (R(2)=0.419; p<0.001). These data support the hypothesis that
      mitochondrial dysfunction is an important feature in MS and of particular
      relevance to the neurodegenerative phase of the disease. Measurement of serum
      lactate in MS might be a relative inexpensive test for longitudinal monitoring of
      "virtual hypoxia" in MS and also a secondary outcome for treatment trials aimed
      to improve mitochondrial function in patients with MS. 

PMID- 24726947
TI  - Cerebellar ataxia and functional genomics: Identifying the routes to cerebellar
      neurodegeneration.
AB  - Cerebellar ataxias are progressive neurodegenerative disorders characterized by
      atrophy of the cerebellum leading to motor dysfunction, balance problems, and
      limb and gait ataxia. These include among others, the dominantly inherited
      spinocerebellar ataxias, recessive cerebellar ataxias such as Friedreich's
      ataxia, and X-linked cerebellar ataxias. Since all cerebellar ataxias display
      considerable overlap in their disease phenotypes, common pathological pathways
      must underlie the selective cerebellar neurodegeneration. Therefore, it is
      important to identify the molecular mechanisms and routes to neurodegeneration
      that cause cerebellar ataxia. In this review, we discuss the use of functional
      genomic approaches including whole-exome sequencing, genome-wide gene expression
      profiling, miRNA profiling, epigenetic profiling, and genetic modifier screens to
      reveal the underlying pathogenesis of various cerebellar ataxias. These
      approaches have resulted in the identification of many disease genes, modifier
      genes, and biomarkers correlating with specific stages of the disease. This
      article is part of a Special Issue entitled: From Genome to Function.

PMID- 24726948
TI  - Rebuttal: Relationship of left ventricular hypertrophy, age, and renal artery
      stenosis.

PMID- 24726949
TI  - Diagnosis and treatment of stage 1 hypertension: which guidelines should we
      follow?

PMID- 24726950
TI  - Use of complementary and alternative medicine in an urban county hospital
      epilepsy clinic.
AB  - We examined self-reported complementary and alternative medicine (CAM) use among
      a largely indigent population with epilepsy. Overall CAM use was 70%, with the
      most frequently reported complementary and alternative medicines (CAMs) being
      medical marijuana (33%), prayer/spirituality (31%), meditation (19%), vitamins
      (19%), and stress management (16%). Forty-four percent of patients reported
      improved seizure control with CAMs. Stress management accounted for perceived
      seizure reduction in 74%, followed by marijuana (54%), prayer (49%), and yoga
      (42%). Among the most commonly used and helpful CAMs, stress management was not
      associated with specific demographic or clinical variables; marijuana use was
      significantly associated with lower age (users=35.2+/-10 years vs.
      nonusers=41.6+/-12; p<0.01) and lower income (under $15,000 40% use vs. 14% over
      $15,000; p<0.05); and prayer was significantly associated with female gender
      (male=21% vs. female=45%; p<0.01) and Black ethnicity (Black=55% vs. Hispanic=30%
      vs. White=23%; p<0.05). Taken together, our study was notable for the high rate
      of CAM utilization in a largely indigent population, with high rates of perceived
      efficacy among several CAM modalities.

PMID- 24726951
TI  - Diagnostic yield of inpatient video-electroencephalographic monitoring:
      experience from a Chinese comprehensive epilepsy center.
AB  - Video-electroencephalographic monitoring (VEEG) is useful in the diagnosis of
      seizure disorders; however, its diagnostic yield in developing countries is not
      well known. The current study retrospectively reviewed the charts of 484
      consecutive patients who were admitted to our center between July 2012 and
      September 2013. Of these patients, 298 (61.6%) were admitted for diagnostic
      clarification and underwent VEEG for a mean duration of 1.3days (range=1-9days).
      The patients were divided into two groups: those whose diagnosis was changed and
      those whose diagnosis was not changed as a result of VEEG. A patient with a
      preadmission diagnosis of epilepsy who was discharged with a diagnosis of
      nonepileptic events (NEEs) or who was further classified as focal/generalized
      epilepsy on discharge was included in the "change in diagnosis" group. A patient
      admitted with an uncertain diagnosis and discharged with a diagnosis of NEEs or
      epilepsy (including focal epilepsy and generalized epilepsy) was also included in
      the "change in diagnosis" group. Video-electroencephalographic monitoring
      recorded typical ictal events (epileptic events or nonepileptic events) in 147
      (49.3%) of the patients admitted for diagnostic clarification. In total, 181
      (60.7%) patients had a change in diagnosis after VEEG. Among them, 103 (56.9%)
      patients had a preadmission diagnosis of epilepsy, which was further classified
      as focal epilepsy (88 patients) or generalized epilepsy (15 patients); the
      diagnosis of NEEs and epilepsy was clarified in 78 (43.1%) patients. The number
      of patients diagnosed with NEEs increased from 31 (10.4%) on admission to 88
      (29.5%) on discharge. Among all the patients admitted for diagnostic
      clarification, therapeutic plans were changed for 104 (57.5%) patients. In 117
      (39.3%) patients with no diagnostic change, VEEG evaluation provided confirmative
      diagnostic information in 47 (15.8%) patients and no additional diagnostic
      information in 70 (23.5%) patients. The study indicates that VEEG is useful in
      terms of clarifying seizure diagnoses and evaluating seizure frequency. In our
      cohort study, VEEG of a relatively short mean duration produced a comparable
      diagnostic yield as that reported in other studies. 

PMID- 24726952
TI  - Matricellular proteins in development: perspectives from the Drosophila heart.
AB  - The Drosophila model represents an attractive system in which to study the
      functional contribution of specific genes to organ development. Within the
      embryo, the heart tube serves as an informative developmental paradigm to analyze
      functional aspects of matricellular proteins. Here, we describe two essential
      extracellular matricellular proteins, Multiplexin (Mp) and Lonely heart (Loh).
      Each of these proteins contributes to the development and morphogenesis of the
      heart tube by regulating the activity/localization of essential extracellular
      proteins. Mp, which is secreted by heart cardioblasts and is specifically
      distributed in the lumen of the heart tube, binds to the signaling protein Slit,
      and facilitates its local signaling at the heart's luminal domain. Loh is an
      ADAMTS-like protein, which serves as an adapter protein to Pericardin (a collagen
      like protein), promoting its specific localization at the abluminal domain of the
      heart tube. We also introduce the Drosophila orthologues of matricellular
      proteins present in mammals, including Thrombospondin, and SPARC, and discuss a
      possible role for Teneurins (Ten-A and Ten-M) in the heart. Understanding the
      role of these proteins provides a novel developmental perspective into the
      functional contribution of matricellular proteins to organ development. 

PMID- 24726954
TI  - Use of a Google Map Tool Embedded in an Internet Survey Instrument: Is it a Valid
      and Reliable Alternative to Geocoded Address Data?
AB  - BACKGROUND: Men who have sex with men (MSM) in the United States are at high risk
      for human immunodeficiency virus (HIV) and poor HIV related outcomes. Maps can be
      used to identify, quantify, and address gaps in access to HIV care among HIV
      positive MSM, and tailor intervention programs based on the needs of patients
      being served. OBJECTIVE: The objective of our study was to assess the usability
      of a Google map question embedded in a Web-based survey among Atlanta-based, HIV
      positive MSM, and determine whether it is a valid and reliable alternative to
      collection of address-based data on residence and last HIV care provider.
      METHODS: Atlanta-based HIV-positive MSM were recruited through Facebook and from
      two ongoing studies recruiting primarily through venue-based sampling or peer
      referral (VBPR). Participants were asked to identify the locations of their
      residence and last attended HIV care provider using two methods: (1) by entering
      the street address (gold standard), and (2) "clicking" on the locations using an
      embedded Google map. Home and provider addresses were geocoded, mapped, and
      compared with home and provider locations from clicked map points to assess
      validity. Provider location error values were plotted against home location error
      values, and a kappa statistic was computed to assess agreement in degree of error
      in identifying residential location versus provider location. RESULTS: The median
      home location error across all participants was 0.65 miles (interquartile range,
      IQR, 0.10, 2.5 miles), and was lower among Facebook participants (P<.001), whites
      (P<.001), and those reporting higher annual household income (P=.04). Median home
      location error was lower, although not statistically significantly, among older
      men (P=.08) and those with higher educational attainment (P=.05). The median
      provider location error was 0.32 miles (IQR, 0.12, 1.2 miles), and did not vary
      significantly by age, recruitment method, race, income, or level of educational
      attainment. Overall, the kappa was 0.20, indicating poor agreement between the
      two error measures. However, those recruited through Facebook had a greater level
      of agreement (kappa=0.30) than those recruited through VBPR methods (kappa=0.16),
      demonstrating a greater level of consistency in using the map question to
      identify home and provider locations for Facebook-recruited individuals.
      CONCLUSIONS: Most participants were able to click within 1 mile of their home
      address and their provider's office, and were not always able to identify the
      locations on a map consistently, although some differences were observed across
      recruitment methods. This map tool may serve as the basis of a valid and reliable
      tool to identify residence and HIV provider location in the absence of geocoded
      address data. Further work is needed to improve and compare map tool usability
      with the results from this study.

PMID- 24726953
TI  - Fat depot-specific gene signature and ECM remodeling of Sca1(high) adipose
      derived stem cells.
AB  - Stem cell antigen-1 (Sca1 or Ly6A/E) is a cell surface marker that is widely
      expressed in mesenchymal stem cells, including adipose-derived stem cells (ASCs).
      We hypothesized that the fat depot-specific gene signature of Sca1(high) ASCs may
      play the major role in defining adipose tissue function and extracellular matrix
      (ECM) remodeling in a depot-specific manner. Herein we aimed to characterize the
      unique gene signature and ECM remodeling of Sca1(high) ASCs isolated from
      subcutaneous (inguinal) and visceral (epididymal) adipose tissues. Sca1(high)
      ASCs are found in the adventitia and perivascular areas of adipose tissues.
      Sca1(high) ASCs purified with magnetic-activated cell sorting (MACS) demonstrate
      dendrite or round shape with the higher expression of cytokines and chemokines
      (e.g., Il6, Cxcl1) and the lower expression of a glucose transporter (Glut1).
      Subcutaneous and visceral fat-derived Sca1(high) ASCs particularly differ in the
      gene expressions of adhesion and ECM molecules. While the expression of the major
      membrane-type collagenase (MMP14) is comparable between the groups, the
      expressions of secreted collagenases (MMP8 and MMP13) are higher in visceral
      Sca1(high) ASCs than in subcutaneous ASCs. Consistently, slow but focal MMP
      dependent collagenolysis was observed with subcutaneous adipose tissue-derived
      vascular stromal cells, whereas rapid and bulk collagenolysis was observed with
      visceral adipose tissue-derived cells in MMP-dependent and -independent manners.
      These results suggest that the fat depot-specific gene signatures of ASCs may
      contribute to the distinct patterns of ECM remodeling and adipose function in
      different fat depots. 

PMID- 24726955
TI  - Selenoprotein W enhances skeletal muscle differentiation by inhibiting TAZ
      binding to 14-3-3 protein.
AB  - Selenoprotein W (SelW) is expressed in various tissues, particularly in skeletal
      muscle. We have previously reported that SelW is up-regulated during C2C12
      skeletal muscle differentiation and inhibits binding of 14-3-3 to its target
      proteins. 14-3-3 reduces myogenic differentiation by inhibiting nuclear
      translocation of transcriptional co-activator with PDZ-binding motif (TAZ).
      Phosphorylation of TAZ at Ser89 is required for binding to 14-3-3, leading to
      cytoplasmic retention of TAZ and a delay in myogenic differentiation. Here, we
      show that myogenic differentiation was delayed in SelW-knockdown C2C12 cells.
      Down-regulation of SelW also increased TAZ binding to 14-3-3, which eventually
      resulted in decreasing translocation of TAZ to the nucleus. However,
      phosphorylation of TAZ at Ser89 was not affected. Although phosphorylation of TAZ
      at Ser89 was sustained by the phosphatase inhibitor okadaic acid, nuclear
      translocation of TAZ was increased by ectopic expression of SelW. This result was
      due to decreased binding of TAZ to 14-3-3. We also found that the interaction
      between TAZ and MyoD was increased by ectopic expression of SelW. Taken together,
      these findings strongly demonstrate that SelW enhances C2C12 cell differentiation
      by inhibiting TAZ binding to 14-3-3. 

PMID- 24726957
TI  - The biological and electrical trade-offs related to the thickness of conducting
      polymers for neural applications.
AB  - Poly(3,4-ethylenedioxythiophene) (PEDOT) films have attracted substantial
      interest as coatings for platinum neuroprosthetic electrodes due to their
      excellent chemical stability and electrical properties. This study systematically
      examined PEDOT coatings formed with different amounts of charge and dopant ions,
      and investigated the combination of surface characteristics that were optimal for
      neural cell interactions. PEDOT samples were fabricated by varying the
      electrodeposition charge from 0.05 to 1 C cm(-2). Samples were doped with either
      poly(styrenesulfonate), tosylate (pTS) or perchlorate. Scanning electron
      micrographs revealed that both thickness and nodularity increased as the charge
      used to produce the sample was increased, and larger dopants produced smoother
      films across all thicknesses. X-ray photoelectron spectroscopy confirmed that the
      amount of charge directly corresponded to the thickness and amount of dopant in
      the samples. Additionally, with increased thickness and nodularity, the
      electrochemical properties of all PEDOT coatings improved. However, neural cell
      adhesion and outgrowth assays revealed that there is a direct biological tradeoff
      related to the thickness and nodularity. Cell attachment, growth and
      differentiation was poorer on the thicker, rougher samples, but thin, less
      nodular PEDOT films exhibited significant improvements over bare platinum.
      PEDOT/pTS fabricated with a charge density of <0.1Ccm(-2) provided superior
      electrochemical and biological properties over conventional platinum electrodes
      and would be the most suitable conducting polymer for neural interface
      applications.

PMID- 24726956
TI  - Development of optical probes for in vivo imaging of polarized macrophages during
      foreign body reactions.
AB  - Plasticity of macrophage (MPhi) phenotypes exist in a spectrum from classically
      activated (M1) cells, to alternatively activated (M2) cells, contributing to both
      the normal healing of tissues and the pathogenesis of implant failure. Here,
      folate- and mannose-based optical probes were fabricated to simultaneously
      determine the degree of MPhi polarization. In vitro tests show the ability of
      these probes to specifically target M1 and M2 cells. In an in vivo murine model,
      they were able to distinguish between the M1-dominated inflammatory response to
      infection and the M2-dominated regenerative response to particle implants.
      Finally, the probes were used to assess the inflammatory/regenerative properties
      of biomaterial implants. Our results show that these probes can be used to
      monitor and quantify the dynamic processes of MPhi polarization and their role in
      cellular responses in real time. 

PMID- 24726958
TI  - In vitro response of macrophage polarization to a keratin biomaterial.
AB  - Macrophage response to biomaterials is emerging as a major focus in tissue repair
      and wound healing. Macrophages are able to differentiate into two distinct
      states, eliciting divergent effects. The M1 phenotype is considered pro
      inflammatory and up-regulates activity related to tissue destruction, whereas the
      M2 phenotype is considered anti-inflammatory and supports tissue remodeling. Both
      are necessary but a fine balance must be maintained as dysregulation of naive
      macrophages to M1 or M2 polarization has been implicated in several disease and
      injury models, and has been suggested as a potential cause for poor outcomes.
      Keratin biomaterials have been shown using different animal models to promote
      regeneration in several tissues. A potential common mechanism may be the general
      capability for keratin biomaterials to elicit beneficial inflammatory responses
      during the early stages of regeneration. In the present study, a keratin
      biomaterial was utilized in vitro to examine its effects on polarization toward
      one of these two macrophage phenotypes, and thus its role in inflammation.
      Exposure of a monocytic cell line to keratin biomaterial substrates was shown to
      bias macrophages toward an M2 phenotype, while a collagen control surface
      produced both M1 and M2 macrophages. Furthermore, keratin treatment was similar
      to the M2 positive control and was similarly effective at down-regulating the M1
      response. Keratin biomaterial influenced greater production of anti-inflammatory
      cytokines and decreased amounts of pro-inflammatory cytokines. The use of a
      keratin biomaterial in regenerative medicine may therefore provide additional
      benefit by regulating a positive remodeling response. 

PMID- 24726959
TI  - Development of an arginine-based cationic hydrogel platform: Synthesis,
      characterization and biomedical applications.
AB  - A series of biodegradable and biocompatible cationic hybrid hydrogels was
      developed from water-soluble arginine-based unsaturated polymer (Arg-AG) and
      poly(ethylene glycol) diacrylate (PEG-DA) by a photocrosslinking method. The
      physicochemical, mechanical and biological properties of these hydrogels were
      intensively examined. The hydrogels were characterized in terms of equilibrium
      swelling ratio (Qeq), compression modulus and interior morphology. The effects of
      the chemical structure of the two Arg-AG precursors and the feed ratio of these
      precursors on the properties of resulting hybrid hydrogels were investigated. The
      crosslinking density and mechanical strength of the hybrid hydrogels increased
      with an increase in allylglycine (AG) content in the Arg-AG precursor, as the
      gelation efficiency (Gf) increased from 80% to 90%, but the swelling and pore
      size of the hybrid hydrogels decreased as the equilibrium swelling weight (Qeq)
      decreased from 1890% to 1330% and the pore size from 28 to 22 MUm. The short-term
      in vitro biodegradation properties of hydrogels were investigated as a function
      of Arg-AG chemical structures and enzymes. Hybrid hydrogels showed faster
      biodegradation in an enzyme solution than in a phosphate-buffered saline
      solution. Bovine serum albumin and insulin release profiles indicated that this
      cationic hydrogel system could significantly improve the sustained release of the
      negatively charged proteins. The cellular response of the hybrid hydrogels was
      preliminarily evaluated by cell attachment, encapsulation and proliferation tests
      using live-dead and MTT assay. The results showed that the hybrid hydrogels
      supported cell attachment well and were nontoxic to the cells.

PMID- 24726960
TI  - Molecular identification of four phenotypes of human Demodex in China.
AB  - Traditional classification of Demodex mites by hosts and phenotypic
      characteristics is defective because of environmental influences. In this study,
      we proposed molecular identification of four phenotypes of two human Demodex
      species based on mitochondrial cox1 fragments for the first time. Mites collected
      from sufferers' facial skin were classified into four phenotypes: phenotype A-C
      with finger-like terminus, and phenotype D with cone-like terminus. The results
      of molecular data showed that cox1 sequences were all 429 bp. Divergences,
      genetic distances and transition/transversion ratios among the three phenotypes
      with finger-like terminus were 0.0-3.0%, 0.000-0.031, and 6/3-5/0, respectively,
      in line with intraspecific differences. However, those measures between the
      phenotype with cone-like terminus and phenotypes with finger-like terminus were
      19.6-20.5%, 0.256-0.271, and 0.58 (31/53)-0.66 (35/53), respectively, reaching
      interspecific level. Phylogenetic trees also showed that the three phenotypes
      with finger-like terminus clustered as one clade, and the phenotype with cone
      like terminus formed another one. Therefore, we conclude that mitochondrial cox1
      sequence is a good marker for identification of two human Demodex species.
      Molecular data indicate no subspecies differentiation. Terminus is an effective
      character for species identification. Mites with finger-like terminus are Demodex
      folliculorum, and those with cone-like terminus are Demodex brevis.

PMID- 24726961
TI  - Effective management for acidic pollution in the canal network of the Mekong
      Delta of Vietnam: a modeling approach.
AB  - Acidic pollution can cause severe environmental consequences annually in coastal
      areas overlain with acid sulfate soils (ASS). A water quality model was used as
      an analytical tool for exploring the effects of water management options and
      other interventions on acidic pollution and salinity in Bac Lieu, a coastal
      province of the Mekong Delta. Fifty eight percent of the provincial area is
      covered by ASS, and more than three-fourths (approximately 175,000 ha) are used
      for brackish-water shrimp culture. Simulations of acid water propagation in the
      canal network indicate that the combination of opening the two main sluices along
      the East Sea of the study area at high tide for one day every week in May and
      June and widening the canals that connect these sluices to the West Sea allows
      for adequate saline water intake and minimizes the acidic pollution in the study
      area. On the other hand, canal dredging in the freshwater ASS area should be done
      properly as it can create severe acidic pollution.

PMID- 24726962
TI  - NH3 biofiltration of piggery air.
AB  - An aboveground pilot-scale biofilter filled with wood chips was tested to treat
      ammonia emissions from a piggery located in Brittany (France). Two long-term
      tests ("summer" and "autumn" experiments) were carried out to improve biofilter
      applications for agriculture. The influence of climatic conditions on biofilter
      performance was taken into account. During summer 2012, the biofilter was
      operated for 74 days at different empty bed residence times (EBRTs) from 6 to 15
      s. Inlet NH3 concentrations were relatively constant (around 15 mg m(-3)).
      Significant NH3 reductions were achieved at EBRT = 12 s (removal efficiencies,
      RE, ranged between 90 and 100% for loading rates, LR, of around 4 g m(-3) h(-1)).
      At a lower EBRT (6 s), RE dropped to roughly 30-50%. This was due to the dramatic
      increase in the loading rate (LR up to 12 g m(-3) h(-1)) but the results showed
      that the change in atmospheric conditions (temperature and relative humidity)
      also had a significant influence on biofilter performance. It was evidenced that
      the use of a humidifier upstream of the biofilter must be taken into account for
      large-scale biofilter design, but only for specific conditions (the spraying of
      the biofilter having to be carried out exceptionally). During autumn 2012, the
      biofilter was operated for 116 days at EBRT = 12 s. RE were around 80% for LR of
      around 3 g m(-3) h(-1). In such autumnal atmospheric conditions, a demister
      system should be installed upstream of the biofilter in order to avoid water
      accumulation in the bed material. Although biofiltration was suitable for NH3
      treatment of piggery air, the need to control accurately the medium moisture
      content implies that biofilters would not be easily managed by a pig farmer.

PMID- 24726963
TI  - Chemometrics quality assessment of wastewater treatment plant effluents using
      physicochemical parameters and UV absorption measurements.
AB  - Chemometric techniques like Principal Component Analysis (PCA) and Partial Least
      Squares Regression (PLS) are used to explore, analyze and model relationships
      among different water quality parameters in wastewater treatment plants (WWTP).
      Different data sets generated by laboratory analysis and by an automatic multi
      parametric monitoring system with a new designed optical device have been
      investigated for temporal variations on water quality parameters measured in the
      water influent and effluent of a WWTP over different time scales. The obtained
      results allowed the discovery of the more important relationships among the
      monitored parameters and of their cyclic dependence on time (daily, monthly and
      annual cycles) and on different plant management procedures. This study intended
      also the modeling and prediction of concentrations of several water components
      and parameters, especially relevant for water quality assessment, such as
      Dissolved Organic Matter (DOM), Total Organic Carbon (TOC) nitrate, detergent,
      and phenol concentrations. PLS models were built to correlate target
      concentrations of these constituents with UV spectra measured in samples
      collected at (1) laboratory conditions (in synthetic water mixtures); and at (2)
      WWTP conditions (in real water samples from the plant). Using synthetic water
      mixtures, specific wavelengths were selected with the aim to establish simple and
      reliable prediction models, which gave good relative predictions with errors of
      around 3-4% for nitrates, detergent and phenols concentrations and of around 15%
      for the DOM in external validation. In the case of nitrate and TOC concentrations
      modeling in real water samples from the effluent of the WWTP using the reduced
      spectral data set, results were also promising with low prediction errors (less
      than 20%).

PMID- 24726964
TI  - Accelerated ageing of an EAF black slag by carbonation and percolation for long
      term behaviour assessment.
AB  - The efficient reuse of industrial by-products, such as the electric arc furnace
      (EAF) black slag, is still hindered by concern over their long-term behaviour in
      outdoor environments. The aim of this study was to develop an accelerated ageing
      method to simulate the long-term natural carbonation of EAF slag exposed to the
      elements. The degree of carbonation achieved in a freshly produced slag after
      accelerated ageing and in a slag used on a fifteen-year-old unpaved road was very
      similar. The influence of particle size on accelerated carbonation was assessed,
      with it being concluded that the slag sample with a particle size bigger than 5-6
      mm underwent slight carbonation over time when it was exposed to CO2. The
      accelerated ageing procedure based on percolating a previously carbonated water
      solution through the slag column allowed gradual leaching with simulated acid
      rain, as well as providing information about the gradual and total chemical
      release from the slag. Three classification groups were established according to
      the release rate of the determined elements. The joint use of the accelerated
      carbonation method and the percolation test is proposed as a useful tool for
      environmental risk assessment concerning the long-term air exposure of EAF black
      slag.

PMID- 24726965
TI  - A Risk Assessment Model for Water Resources: releases of dangerous and hazardous
      substances.
AB  - Many dangerous and hazardous substances are used, transported and handled daily
      in diverse situations, from domestic use to industrial processing, and during
      those operations, spills or other anomalous situations may occur that can lead to
      contaminant releases followed by contamination of surface water or groundwater
      through direct or indirect pathways. When dealing with this problem, rapid,
      technically sound decisions are desirable, and the use of complex methods may not
      be able to deliver information quickly. This work describes a simple conceptual
      model established on multi-criteria based analysis involving a strategic
      appraisal for contamination risk assessment to support local authorities on rapid
      technical decisions. The model involves a screening for environmental risk
      sources, focussing on persistent, bioaccumulative and toxic (PBT) substances that
      may be discharged into water resources. It is a simple tool that can be used to
      follow-up actual accident scenarios in real time and to support daily activities,
      such as site-inspections.

PMID- 24726966
TI  - Environmental life cycle assessment of different domestic wastewater streams:
      policy effectiveness in a tropical urban environment.
AB  - To enhance local water security, the Singapore government promotes two water
      conservation policies: the use of eco-friendly toilets to reduce yellow water
      (YW) disposal and the installation of water efficient devices to minimize gray
      water (GW) discharge. The proposed water conservation policies have different
      impacts on the environmental performance of local wastewater management. The main
      purpose of this study is to examine and compare the impacts of different domestic
      wastewater streams and the effectiveness of two water conservation policies by
      means of life cycle assessment (LCA). LCA is used to compare three scenarios,
      including a baseline scenario (BL), YW-reduced scenario (YWR) and GW-reduced
      scenario (GWR). The BL is designed based on the current wastewater management
      system, whereas the latter two scenarios are constructed according to the two
      water conservation policies that are proposed by the Singapore government. The
      software SIMPARO 7.3 with local data and an eco-invent database is used to build
      up the model, and the functional unit is defined as the daily wastewater disposal
      of a Singapore resident. Due to local water supply characteristics, the system
      boundary is extended to include the sewage sludge management and tap water
      production processes. The characterization results indicate that the GWR has a
      significant impact reduction (22-25%) while the YWR has only a 2-4% impact
      reduction compared with the BL. The contribution analysis reveals that the GW
      dominates many impact categories except eutrophication potential. The tap water
      production is identified as the most influential process due to its high embodied
      energy demand in a local context. Life cycle costing analysis shows that both YWR
      and GWR are financially favorable. It is also revealed that the current water
      conservation policies could only achieve Singapore's short-term targets.
      Therefore, two additional strategies are recommended for achieving long-term
      goals. This study provides a comprehensive and reliable environmental profile of
      Singapore's wastewater management with the help of extended system boundary and
      local data. This work also fills the research gap of previous studies by
      identifying the contribution of different wastewater streams, which would serve
      as a good reference for source-separating sanitation system design.

PMID- 24726967
TI  - Desalination feasibility study of an industrial NaCl stream by bipolar membrane
      electrodialysis.
AB  - The industrial implementation of alternative technologies in the processing of
      saline effluent streams is a topic of growing importance. In this technical
      feasibility study, the desalination of an industrial saline stream containing
      about 75 g L(-1) NaCl contaminated with some organic matter using bipolar
      membrane electrodialysis (EDBM) was investigated on lab-scale. Bipolar membranes
      of two different manufacturers (PCA - PolymerChemie Altmeier GmbH and FuMA-Tech
      GmbH) were tested and compared in terms of electrical resistance, current
      efficiency and purity of the produced acid and base stream. In both cases, almost
      complete desalination (>99%) was achieved and simultaneously HCl and NaOH were
      produced with a concentration between 1.5 and 2 M with a relatively good purity.
      The Fumasep bipolar membranes scored slightly better for electrical resistance
      and current efficiency. On the other hand, slightly higher current densities were
      achieved with PCA bipolar membranes. Simultaneously, some information was
      obtained on the transport behavior of the organic matter present in the saline
      stream. It was observed that a transport competition occurred between the organic
      matter and the accompanying chlorides. From this lab-scale study it was concluded
      that EDBM is a promising and attractive technology in the area of saline effluent
      reclamation and reuse.

PMID- 24726968
TI  - Improvement of mesophilic anaerobic co-digestion of agri-food waste by addition
      of glycerol.
AB  - Anaerobic co-digestion is a promising alternative to manage agri-food waste
      rather than landfilling, composting or incineration. But improvement of methane
      yield and biodegradability is often required to optimize its economic viability.
      Biomethanization of agri-food solid waste presents the disadvantage of a slow
      hydrolytic phase, which might be enhanced by adding a readily digestible
      substrate such as glycerol. In this study, strawberry extrudate, fish waste and
      crude glycerol derived from biodiesel manufacturing are mixed at a proportion of
      54:5:41, in VS (VS, total volatile solids), respectively. The mesophilic
      anaerobic co-digestion at lab-scale of the mixture was stable at loads lower than
      1.85 g VS/L, reaching a methane yield coefficient of 308 L CH4/kg VS (0  degrees
      C, 1 atm) and a biodegradability of 96.7%, in VS. Moreover, the treatment
      capacity of strawberry and fish waste was increased 16% at adding the crude
      glycerol. An economic assessment was also carried out in order to evaluate the
      applicability of the proposed process. Even in a pessimistic scenario, the net
      balance was found to be positive. The glycerol adding implied a net saving in a
      range from 25.5 to 42.1 ?/t if compared to landfill disposal.

PMID- 24726969
TI  - Using CV-GLUE procedure in analysis of wetland model predictive uncertainty.
AB  - This study develops a procedure that is related to Generalized Likelihood
      Uncertainty Estimation (GLUE), called the CV-GLUE procedure, for assessing the
      predictive uncertainty that is associated with different model structures with
      varying degrees of complexity. The proposed procedure comprises model
      calibration, validation, and predictive uncertainty estimation in terms of a
      characteristic coefficient of variation (characteristic CV). The procedure first
      performed two-stage Monte-Carlo simulations to ensure predictive accuracy by
      obtaining behavior parameter sets, and then the estimation of CV-values of the
      model outcomes, which represent the predictive uncertainties for a model
      structure of interest with its associated behavior parameter sets. Three commonly
      used wetland models (the first-order K-C model, the plug flow with dispersion
      model, and the Wetland Water Quality Model; WWQM) were compared based on data
      that were collected from a free water surface constructed wetland with paddy
      cultivation in Taipei, Taiwan. The results show that the first-order K-C model,
      which is simpler than the other two models, has greater predictive uncertainty.
      This finding shows that predictive uncertainty does not necessarily increase with
      the complexity of the model structure because in this case, the more simplistic
      representation (first-order K-C model) of reality results in a higher uncertainty
      in the prediction made by the model. The CV-GLUE procedure is suggested to be a
      useful tool not only for designing constructed wetlands but also for other
      aspects of environmental management.

PMID- 24726970
TI  - Demonstrating a new framework for the comparison of environmental impacts from
      small- and large-scale hydropower and wind power projects.
AB  - Climate change and the needed reductions in the use of fossil fuels call for the
      development of renewable energy sources. However, renewable energy production,
      such as hydropower (both small- and large-scale) and wind power have adverse
      impacts on the local environment by causing reductions in biodiversity and loss
      of habitats and species. This paper compares the environmental impacts of many
      small-scale hydropower plants with a few large-scale hydropower projects and one
      wind power farm, based on the same set of environmental parameters; land
      occupation, reduction in wilderness areas (INON), visibility and impacts on red
      listed species. Our basis for comparison was similar energy volumes produced,
      without considering the quality of the energy services provided. The results show
      that small-scale hydropower performs less favourably in all parameters except
      land occupation. The land occupation of large hydropower and wind power is in the
      range of 45-50 m(2)/MWh, which is more than two times larger than the small-scale
      hydropower, where the large land occupation for large hydropower is explained by
      the extent of the reservoirs. On all the three other parameters small-scale
      hydropower performs more than two times worse than both large hydropower and wind
      power. Wind power compares similarly to large-scale hydropower regarding land
      occupation, much better on the reduction in INON areas, and in the same range
      regarding red-listed species. Our results demonstrate that the selected four
      parameters provide a basis for further development of a fair and consistent
      comparison of impacts between the analysed renewable technologies.

PMID- 24726971
TI  - The economics of roadside bear viewing.
AB  - Viewing bears along roadside habitats is a popular recreational activity in
      certain national parks throughout the United States. However, safely managing
      visitors during traffic jams that result from this activity often requires the
      use of limited park resources. Using unique visitor survey data, this study
      quantifies economic values associated with roadside bear viewing in Yellowstone
      National Park, monetary values that could be used to determine whether this
      continued use of park resources is warranted on economic grounds. Based on
      visitor expenditure data and results of a contingent visitation question, it is
      estimated that summer Park visitation would decrease if bears were no longer
      allowed to stay along roadside habitats, resulting in a loss of 155 jobs in the
      local economy. Results from a nonmarket valuation survey question indicate that
      on average, visitors to Yellowstone National Park are willing to pay around $41
      more in Park entrance fees to ensure that bears are allowed to remain along roads
      within the Park. Generalizing this value to the relevant population of visitors
      indicates that the economic benefits of allowing this wildlife viewing
      opportunity to continue could outweigh the costs of using additional resources to
      effectively manage these traffic jams. 

PMID- 24726972
TI  - Paced QT interval is a better predictor of mortality than the intrinsic QT
      interval: long-term follow-up study.
AB  - BACKGROUND: Prolongation of the corrected QT (QTc) interval on 12-lead
      electrocardiogram is related to total mortality and sudden cardiac death. The
      value of the paced QTc interval in predicting mortality has not been
      investigated. OBJECTIVE: To evaluate the relationship between the paced QTc
      interval and mortality. METHODS: Of 1440 patients who underwent pacemaker
      implantation from January 1990 to March 2010, 766 had a recorded intrinsic and
      ventricular paced rhythm and were included in this study. The intrinsic and paced
      QTc intervals were measured on 12-lead electrocardiogram before and 1-month after
      implantation. RESULTS: During a mean follow-up period of 7 +/- 5 years, 189
      (24.4%) patients died, of which 63 (8.1%) were cardiac deaths. Compared with
      patients in the first tertile of the paced QTc interval (<484 ms), patients in
      the third tertile (>511 ms) were significantly more likely to die (19% vs 29%; P
      < .05). A comparison of the third and first tertiles of the QTc interval showed
      that a prolonged paced QTc interval was a significant independent predictor of
      all-cause mortality (adjusted hazard ratio 2.08; 95% confidence interval 1.44
      3.01; P < .001) and cardiac mortality (adjusted hazard ratio 2.53; 95% confidence
      interval 1.29-4.95; P = .007) and a better predictor than was a prolonged
      intrinsic QTc interval. When treated as a continuous variable, a prolonged paced
      QTc interval predicted increased total mortality and cardiac mortality.
      CONCLUSION: The paced QTc interval appears to be a more useful marker in
      predicting bad prognosis than does the intrinsic QTc interval in patients with
      indications for a permanent pacemaker.

PMID- 24726974
TI  - EP News: Allied Professionals.

PMID- 24726973
TI  - EP News: Basic and Translational.

PMID- 24726975
TI  - Reply to the editor.

PMID- 24726976
TI  - To the editor--Spontaneous conversion of a long RP to short RP tachycardia: what
      is the mechanism?

PMID- 24726977
TI  - Effects of tricalcium silicate cements on osteogenic differentiation of human
      bone marrow-derived mesenchymal stem cells in vitro.
AB  - Tricalcium silicate cements have been successfully employed in the biomedical
      field as bioactive bone and dentin substitutes, with widely acclaimed osteoactive
      properties. This research analyzed the effects of different tricalcium silicate
      cement formulations on the temporal osteoactivity profile of human bone marrow
      derived mesenchymal stem cells (hMW-MSCs). These cells were exposed to four
      commercially available tricalcium silicate cement formulations in osteogenic
      differentiation medium. After 1, 3, 7 and 10 days, quantitative real-time
      polymerase chain reaction and Western blotting were performed to detect
      expression of the target osteogenic markers ALP, RUNX2, OSX, OPN, MSX2 and OCN.
      After 3, 7, 14 and 21 days, alkaline phosphatase assay was performed to detect
      changes in intracellular enzyme level. An Alizarin Red S assay was performed
      after 28 days to detect extracellular matrix mineralization. In the presence of
      tricalcium silicate cements, target osteogenic markers were downregulated at the
      mRNA and protein levels at all time points. Intracellular alkaline phosphatase
      enzyme levels and extracellular mineralization of the experimental groups were
      not significantly different from the untreated control. Quantitative polymerase
      chain reaction results showed increases in downregulation of RUNX2, OSX, MSX2 and
      OCN with increasing time of exposure to the tricalcium silicate cements, while
      ALP showed peak downregulation at day 7. For Western blotting, OSX, OPN, MSX2 and
      OCN showed increased downregulation with increased exposure time to the tested
      cements. Alkaline phosphatase enzyme levels generally declined after day 7. Based
      on these results, it is concluded that tricalcium silicate cements do not induce
      osteogenic differentiation of hBM-MSCs in vitro.

PMID- 24726978
TI  - The surface charge of liposomal adjuvants is decisive for their interactions with
      the Calu-3 and A549 airway epithelial cell culture models.
AB  - One of the main reasons for the unmet medical need for mucosal vaccines is the
      lack of safe and efficacious mucosal adjuvants. The cationic liposome-based
      adjuvant system composed of dimethyldioctadecylammonium (DDA) bromide and
      trehalose 6,6'-dibehenate (TDB) is a versatile adjuvant that has shown potential
      for mucosal vaccination via the airways. The purpose of this study was to
      investigate the importance of the liposomal surface charge on the interaction
      with lung epithelial cells. Thus, the cationic DDA in the liposomes was subjected
      to a step-wise replacement with the zwitterionic distearoylphosphatidylcholine
      (DSPC). The liposomes were tested with the model protein antigen ovalbumin for
      the mucosal deposition, the effect on cellular viability and the epithelial
      integrity by using the two cell lines A549 and Calu-3, representing cells from
      the alveolar and the bronchiolar epithelium, respectively. The Calu-3 cells were
      cultured under different conditions, resulting in epithelia with a low and a high
      mucus secretion, respectively. A significantly larger amount of lipid and
      ovalbumin was deposited in the epithelial cell layer and in the mucus after
      incubation with the cationic liposomes, as compared to incubation with the
      neutral liposomes, which suggests that the cationic charge is important for the
      delivery. The integrity and the viability of the cells without a surface-lining
      mucus layer were decreased upon incubation with the cationic formulations,
      whereas the mucus appeared to retain the integrity and viability of the mucus
      covered Calu-3 cells. Our in vitro results thus indicate that DDA/TDB liposomes
      might be efficiently and safely used as an adjuvant system for vaccines targeting
      the mucus-covered epithelium of the upper respiratory tract and the conducting
      airways. 

PMID- 24726979
TI  - Azoxystrobin, a mitochondrial complex III Qo site inhibitor, exerts beneficial
      metabolic effects in vivo and in vitro.
AB  - BACKGROUND: Several anti-diabetes drugs exert beneficial effects against
      metabolic syndrome by inhibiting mitochondrial function. Although much progress
      has been made toward understanding the role of mitochondrial function inhibitors
      in treating metabolic diseases, the potential effects of these inhibitors on
      mitochondrial respiratory chain complex III remain unclear. METHODS: We
      investigated the metabolic effects of azoxystrobin (AZOX), a Qo inhibitor of
      complex III, in a high-fat diet-fed mouse model with insulin resistance in order
      to elucidate the mechanism by which AZOX improves glucose and lipid metabolism at
      the metabolic cellular level. RESULTS: Acute administration of AZOX in mice
      increased the respiratory exchange ratio. Chronic treatment with AZOX reduced
      body weight and significantly improved glucose tolerance and insulin sensitivity
      in high-fat diet-fed mice. AZOX treatment resulted in decreased triacylglycerol
      accumulation and down-regulated the expression of genes involved in liver
      lipogenesis. AZOX increased glucose uptake in L6 myotubes and 3T3-L1 adipocytes
      and inhibited de novo lipogenesis in HepG2 cells. The findings indicate that AZOX
      mediated alterations to lipid and glucose metabolism may depend on AMP-activated
      protein kinase (AMPK) signaling. CONCLUSIONS: AZOX, a Qo inhibitor of
      mitochondrial respiratory complex III, exerts whole-body beneficial effects on
      the regulation of glucose and lipid homeostasis in high-fat diet-fed mice.
      GENERAL SIGNIFICANCE: These findings provide evidence that a Qo inhibitor of
      mitochondrial respiratory complex III could represent a novel approach for the
      treatment of obesity.

PMID- 24726980
TI  - Review on statistical methods for gene network reconstruction using expression
      data.
AB  - Network modeling has proven to be a fundamental tool in analyzing the inner
      workings of a cell. It has revolutionized our understanding of biological
      processes and made significant contributions to the discovery of disease
      biomarkers. Much effort has been devoted to reconstruct various types of
      biochemical networks using functional genomic datasets generated by high
      throughput technologies. This paper discusses statistical methods used to
      reconstruct gene regulatory networks using gene expression data. In particular,
      we highlight progress made and challenges yet to be met in the problems involved
      in estimating gene interactions, inferring causality and modeling temporal
      changes of regulation behaviors. As rapid advances in technologies have made
      available diverse, large-scale genomic data, we also survey methods of
      incorporating all these additional data to achieve better, more accurate
      inference of gene networks. 

PMID- 24726982
TI  - Primary motor cortex and ipsilateral control: a TMS study.
AB  - In this transcranial magnetic stimulation study, we assessed motor cortex
      excitability in the resting hemisphere while the homologous side was active
      during a voluntary unimanual task. Data acquired from left- and right-handers
      showed that cortical excitability varied as a function of isometric task demands
      and hand dominance. In particular, facilitation of the motor-evoked potentials
      was observed across task requirements in left-handers, independent of which
      hemisphere was active. In right-handers, facilitation was present when the right
      hemisphere was active whereas this effect was largely reduced when the left
      hemisphere was active, suggesting pronounced inhibitory interactions from the
      left (dominant) to the right (non-dominant) hemisphere. The distinct scaling of
      motor cortex excitability indicates the importance of the left hemisphere in
      guiding manual control in right-handers whereas both hemispheres are functionally
      relevant in left-handers. Overall, the results underline the asymmetrical
      organization of the motor system in right-handers with an important role of the
      dominant hemisphere whereas symmetrical functional abilities of both hemispheres
      characterize left-handers. 

PMID- 24726983
TI  - Timing of light pulses and photoperiod on the diurnal rhythm of hippocampal
      neuronal morphology of Siberian hamsters.
AB  - Rapid remodeling of neurons provides the brain with flexibility to adjust to
      environmental fluctuations. In Siberian hamsters, hippocampal dendritic
      morphology fluctuates across the day. To reveal the regulatory mechanism of
      diurnal remodeling of hippocampal neurons, we investigated the effects of light
      signals applied under different photoperiodic conditions on dendritic morphology.
      A 4-h dark pulse during the morning of long days (LD) increased basilar dendritic
      length, as well as complexity of basilar dendrites of neurons in the CA1. A light
      pulse during the late night in short days (SD) reduced basilar dendrite branching
      and increased primary apical dendrites of CA1 neurons. Spine density of dentate
      gyrus (DG) dendrites was increased by a dark pulse in LD and spine density of CA1
      basilar dendrites was decreased by a light pulse in SD. These results indicate
      that light signals induce rapid remodeling of dendritic morphology in a
      hippocampal subregion-specific manner. A light pulse in SD decreased hippocampal
      expression of fetal liver kinase 1 (Flk1), a receptor for vascular endothelial
      growth factor (VEGF), raising the possibility that VEGF-FLK1 signaling might be
      involved in the rapid decrease of branching or spine density of CA1 basilar
      dendrites by light. 

PMID- 24726981
TI  - Administration of S-methyl-L-thiocitrulline protects against brain injuries after
      intracerebral hemorrhage.
AB  - Although intracerebral hemorrhage (ICH) increases the level of glutamate in the
      perihematomal area and cerebral spinal fluid (CSF) in the ICH acute phase, it is
      unclear whether elevated glutamate activates neuronal nitric oxide synthase
      (nNOS) in the ICH brain and whether nNOS is an important target for ICH
      treatment. Here, we assessed the role of the nNOS inhibitor S-methyl-l
      thiocitrulline (SMTC) in the activity of NADPH-d and ICH-induced brain injuries.
      An autologous blood intracerebral infusion model in male rats was used. All of
      the rats were sacrificed 24h after ICH. ICH increased NADPH-d activity in the
      striatum. Administering SMTC 3h after ICH decreased the activity of NADH-d
      (p<0.05 vs. the ICH group). The activation of gelatinolytic enzymes in the
      perihematomal region of the striatum was reduced by SMTC treatment (p<0.01, vs.
      the ICH group). The loss of laminin- and occludin-stained vessels was significant
      in perihematomal regions after 24h of ICH and was significantly attenuated by the
      administration of SMTC (p<0.01 for laminin, p<0.05 for occluding, compared with
      the ICH group). Neuronal death and neurological deficits after ICH were also
      decreased in SMTC treatment rats (p<0.01, vs. the ICH group). The results suggest
      that the administration of the nNOS inhibitor SMTC after ICH protects against ICH
      induced brain injuries and improves neurological function.

PMID- 24726984
TI  - Caffeine triggers behavioral and neurochemical alterations in adolescent rats.
AB  - Caffeine is the psychostimulant most consumed worldwide but concerns arise about
      the growing intake of caffeine-containing drinks by adolescents since the effects
      of caffeine on cognitive functions and neurochemical aspects of late brain
      maturation during adolescence are poorly known. We now studied the behavioral
      impact in adolescent male rats of regular caffeine intake at low (0.1mg/mL),
      moderate (0.3mg/mL) and moderate/high (1.0mg/mL) doses only during their active
      period (from 7:00 P.M. to 7:00 A.M.). All tested doses of caffeine were devoid of
      effects on locomotor activity, but triggered anxiogenic effects. Caffeine (0.3
      and 1mg/mL) improved the performance in the object recognition task, but the
      higher dose of caffeine (1.0mg/mL) decreased the habituation to an open-field
      arena, suggesting impaired non-associative memory. All tested doses of caffeine
      decreased the density of glial fibrillary acidic protein and synaptosomal
      associated protein-25, but failed to modify neuron-specific nuclear protein
      immunoreactivity in the hippocampus and cerebral cortex. Caffeine (0.3-1mg/mL)
      increased the density of brain-derived neurotrophic factor (BDNF) and proBDNF
      density as well as adenosine A1 receptor density in the hippocampus, whereas the
      higher dose of caffeine (1mg/mL) increased the density of proBDNF and BDNF and
      decreased A1 receptor density in the cerebral cortex. These findings document an
      impact of caffeine consumption in adolescent rats with a dual impact on anxiety
      and recognition memory, associated with changes in BDNF levels and decreases of
      astrocytic and nerve terminal markers without overt neuronal damage in
      hippocampal and cortical regions. 

PMID- 24726985
TI  - Self-assembling gelling formulation based on a crystalline-phase liquid as a non
      viral vector for siRNA delivery.
AB  - Liquid crystalline systems (LCSs) form interesting drug delivery systems. These
      include in situ gelling delivery systems, which present several advantages for
      use as self-assembling systems for local drug delivery. The aim of this study was
      to develop and characterize in situ gelling delivery systems for local siRNA
      delivery. The influence of the components that form the systems was investigated,
      and the systems were characterized by polarized light microscopy, Small Angle X
      ray Scattering (SAXS), swelling studies, assays of their ability to form a
      complex with genes and of the stability of the genes in the system, as well as
      assays of in situ gelling formation and local toxicity using an animal model. The
      system containing a mixture of monoglycerides (MO), oleylamine (OAM), propylene
      glycol (PG) and tris buffer (8.16:0.34:76.5:15, w/w/w/w) was considered the most
      appropriate for local siRNA delivery purposes. The molecular structure was
      characterized as hexagonal phase; the swelling studies followed a second order
      kinetic model and the water absorption was a fast process reaching equilibrium at
      2 h. The system formed a complex with siRNA and remained in a stable form. The
      gel was formed in vivo after subcutaneous administration of a precursor fluid
      formulation in mice and was biodegradable in 30 days. The inflammatory process
      that took place was considered normal. Therefore, the developed liquid
      crystalline delivery system shows the appropriate characteristics for use as a
      local siRNA delivery method for gene therapy.

PMID- 24726986
TI  - Differential expression of aromatase, estrogen receptor alpha and 17beta-HSD
      associated with the processes of total testicular regression and recrudescence in
      the bat Myotis nigricans (Chiroptera: Vespertilionidae).
AB  - Despite the worldwide distribution and many unique reproductive adaptations that
      bats present, many aspects of their reproductive hormonal regulation have not
      been adequately studied, especially in species that presented patterns of total
      testicular regression. Thus, this study aimed to evaluate the testicular
      expression of 17beta-HSD type 1, aromatase and ERalpha in the bat Myotis
      nigricans, during the four periods of its reproductive cycle. Immunoreactivity
      for ERalpha was detected only in the cytoplasm of elongated spermatids and in the
      nuclei of spermatogonia and Sertoli cells. Expression of aromatase was observed
      in round and elongated spermatids and in Sertoli and Leydig cells.
      Immunoreactivity for 17beta-HSD was restricted to the cytoplasm of Leydig cells.
      The three expression patterns varied significantly during the four periods of the
      reproductive cycle. Expression of ERalpha and aromatase in spermatids was
      continuous, while expression of ERalpha in spermatogonia occurred only in initial
      types (Ap). Expression of ERalpha and aromatase in Sertoli cells varied, with
      expression only in periods of spermatogenetic activities; and the same variation
      was observed for the expression of aromatase and 17beta-HSD in Leydig cells. We,
      therefore, propose that the processes of total testicular regression and
      posterior recrudescence suffered by M. nigricans from September to January in the
      northwest of the Sao Paulo State of Brazil, are directly regulated by
      testosterone and estrogen. This occurs via the production of testosterone by
      17beta-HSD, its conversion into estrogen by aromatase, and
      activation/deactivation of Sertoli cells' AR and spermatogonia's ERalpha.

PMID- 24726988
TI  - Endocrinology: advances through omics and related technologies.
AB  - The rapid development of new omics technologies to measure changes at genetic,
      transcriptomic, proteomic, and metabolomics levels together with the evolution of
      methods to analyze and integrate the data at a systems level are revolutionizing
      the study of biological processes. Here we discuss how new approaches using omics
      technologies have expanded our knowledge especially in nontraditional models. Our
      increasing knowledge of these interactions and evolutionary pathway conservation
      facilitates the use of nontraditional species, both invertebrate and vertebrate,
      as new model species for biological and endocrinology research. The increasing
      availability of technology to create organisms overexpressing key genes in
      endocrine function allows manipulation of complex regulatory networks such as
      growth hormone (GH) in transgenic fish where disregulation of GH production to
      produce larger fish has also permitted exploration of the role that GH plays in
      testis development, suggesting that it does so through interactions with insulin
      like growth factors. The availability of omics tools to monitor changes at nearly
      any level in any organism, manipulate gene expression and behavior, and integrate
      data across biological levels, provides novel opportunities to explore endocrine
      function across many species and understand the complex roles that key genes play
      in different aspects of the endocrine function. 

PMID- 24726987
TI  - Establishing regional specificity of neuroestrogen action.
AB  - The specificity of estrogen signaling in brain is defined at one level by the
      types and distributions of receptor molecules that are activated by estrogens. At
      another level, as our understanding of the neurobiology of the estrogen synthetic
      enzyme aromatase has grown, questions have emerged as to how neuroactive
      estrogens reach specific target receptors in functionally relevant
      concentrations. Here we explore the spatial specificity of neuroestrogen
      signaling with a focus on studies of songbirds to provide perspective on some as
      yet unresolved questions. Studies conducted in both male and female songbirds
      have helped to clarify these interesting facets of neuroestrogen physiology. 

PMID- 24726989
TI  - Analysis of the pharmacological properties of chicken melanocortin-2 receptor
      (cMC2R) and chicken melanocortin-2 accessory protein 1 (cMRAP1).
AB  - The chicken (Gallus gallus) melanocortin-2 receptor (cMC2R) can be functionally
      expressed in CHO cells when chicken melanocortin-2 receptor accessory protein 1
      (cMRAP1) is co-expressed. The transiently transfected CHO cells responded in a
      robust manner to stimulation by hACTH(1-24) (EC50 value=2.7 * 10(-12)M +/- 1.3 *
      10(-12)), but the transfected CHO cells could not be stimulated by NDP-MSH at
      concentrations as high as 10(-7)M. Incubation of cMC2R/cMRAP1 transfected cells
      with alanine substituted analogs of hACTH(1-24) at amino acid positions F(7) or
      W(9) completely blocked stimulation of the transfected cells. Similarly,
      incubation of cMC2R/cMRAP1 transfected cells with an analog of hACTH(1-24) with
      alanine substitutions at amino acid positions R(17)R(18)P(19) resulted in a 276
      fold shift in EC50 value relative to the positive control (p<0.004). Collectively
      these observations suggest that cMC2R has binding sites for the HFRW motif and
      KKRRP motif of hACTH(1-24), and both motifs are required for full activation of
      the receptor. While previous studies had shown that Anolis carolinensis MC2R and
      Xenopus tropicalis MC2R could be functionally expressed in CHO cells that co
      expressed mouse MRAP1, co-expression of these non-mammalian tetrapod MC2Rs with
      cMRAP1 resulted in a significant increase in sensitivity to hACTH(1-24), as
      measured by EC50 value, for A. carolinensis MC2R (p<0.005) and X. tropicalis MC2R
      (p<0.007). The implications of these observations are discussed.

PMID- 24726990
TI  - VDR primary targets by genome-wide transcriptional profiling.
AB  - There is growing evidence that 1alpha,25-dihydroxyvitamin D3 (1alpha,25(OH)2D3)
      plays a role in breast cancer prevention and survival. It elicits a variety of
      antitumor activities like controlling cellular differentiation, proliferation and
      angiogenesis. Most of its biological effects are exerted via its nuclear receptor
      which acts as a transcriptional regulator. Here, we carried out a genome-wide
      investigation of the primary transcriptional targets of 1alpha,25(OH)2D3 in
      breast epithelial cancer cells using RNA-Seq technology. We identified early
      transcriptional targets of 1alpha,25(OH)2D3 involved in adhesion, growth
      regulation, angiogenesis, actin cytoskeleton regulation, hexose transport,
      inflammation and immunomodulation, apoptosis, endocytosis and signaling.
      Furthermore, we found several transcription factors to be regulated by
      1alpha,25(OH)2D3 that subsequently amplify and diversify the transcriptional
      output driven by 1alpha,25(OH)2D3 leading finally to a growth arrest of the
      cells. Moreover, we could show that 1alpha,25(OH)2D3 elevates the trimethylation
      of histone H3 lysine 4 at several target gene promoters. Our present
      transcriptomic analysis of differential expression after 1alpha,25(OH)2D3
      treatment provides a resource of primary 1alpha,25(OH)2D3 targets that might
      drive the antiproliferative action in breast cancer epithelial cells. 

PMID- 24726991
TI  - Simple, rapid and effective preservation and reactivation of anaerobic ammonium
      oxidizing bacterium "Candidatus Brocadia sinica".
AB  - It is still the biggest challenge to secure enough seeding biomass for rapid
      start-up of full-scale (anaerobic ammonium oxidation) anammox processes due to
      slow growth. Preservation of active anammox biomass could be one of the
      solutions. In this study, biomass of anammox bacterium, "Candidatus Brocadia
      sinica", immersed in various nutrient media were preserved at -80  degrees C, 4 
      degrees C and room temperature. After 45, 90 and 150 days of preservation,
      specific anammox activity (SAA) of the preserved anammox biomass was determined
      by measuring (29)N2 production rate and transcription levels of hzsA gene
      encoding hydrazine synthase alpha subunit. Storage in nutrient medium containing
      3 mM of molybdate at room temperature with periodical (every 45 days) supply of
      NH4(+) and NO2(-) was proved to be the most effective storage technique for "Ca.
      Brocadia sinica" biomass. Using this preservation condition, 96, 92 and 65% of
      the initial SAA was sustained after 45, 90 and 150 days of storage, respectively.
      Transcription levels of hzsA gene in biomass correlated with the SAA (R(2) =
      0.83), indicating it can be used as a genetic marker to evaluate the anammox
      activity of preserved biomass. Furthermore, the 90-day-stored biomass was
      successfully reactivated by immobilizing in polyvinyl alcohol (6%, w/v) and
      sodium alginate (2%, w/v) gel and then inoculated to up-flow column reactors.
      Total nitrogen removal rates rapidly increased to 7 kg-N m(-3) d(-1) within 35
      days of operation. Based on these results, the room temperature preservation with
      molybdate addition is simple, cost-effective and feasible at a practical scale,
      which will accelerate the practical use of anammox process for wastewater
      treatment. 

PMID- 24726992
TI  - Impact of spacer thickness on biofouling in forward osmosis.
AB  - Forward osmosis (FO) indirect desalination systems integrate wastewater recovery
      with seawater desalination. Niche applications for FO systems have been reported
      recently, due to the demonstrated advantages compared to conventional high
      pressure membrane processes such as nanofiltration (NF) and reverse osmosis (RO).
      Among them, wastewater recovery has been identified to be particularly suitable
      for practical applications. However, biofouling in FO membranes has rarely been
      studied in applications involving wastewater effluents. Feed spacers separating
      the membrane sheets in cross-flow systems play an important role in biofilm
      formation. The objective of this study was to determine the influence of feed
      spacer thickness (28, 31 and 46 mil) on biofouling development and membrane
      performance in a FO system, using identical cross-flow cells in parallel studies.
      Flux development, biomass accumulation, fouling localization and composition were
      determined and analyzed. For all spacer thicknesses, operated at the same feed
      flow and the same run time, the same amount of biomass was found, while the flux
      reduction decreased with thicker spacers. These observations are in good
      agreement with biofouling studies for RO systems, considering the key differences
      between FO and RO. Our findings contradict previous cross-flow studies on
      particulate/colloidal fouling, where higher cross-flow velocities improved system
      performance. Thicker spacers reduced the impact of biofouling on FO membrane
      flux. 

PMID- 24726993
TI  - Efficiency of source control systems for reducing runoff pollutant loads:
      feedback on experimental catchments within Paris conurbation.
AB  - Three catchments, equipped with sustainable urban drainage systems (SUDS:
      vegetated roof, underground pipeline or tank, swale, grassed detention pond) for
      peak flow mitigation, have been compared to a reference catchment drained by a
      conventional separate sewer system in terms of hydraulic behaviour and discharged
      contaminant fluxes (organic matter, organic micropollutants, metals). A runoff
      and contaminant emission model has been developed in order to overcome land use
      differences. It has been demonstrated that the presence of peak flow control
      systems induces flow attenuation even for frequent rain events and reduces water
      discharges at a rate of about 50% depending on the site characteristics. This
      research has also demonstrated that this type of SUDS contributes to a
      significant reduction of runoff pollutant discharges, by 20%-80%. This level of
      reduction varies depending on the considered contaminant and on the design of the
      drainage system but is mostly correlated with the decrease in runoff volume. It
      could be improved if the design of these SUDS focused not only on the control of
      exceptional events but also targeted more explicitly the interception of frequent
      rain events. 

PMID- 24726994
TI  - Influence of temperature and pretreatments on the anaerobic digestion of
      wastewater grown microalgae in a laboratory-scale accumulating-volume reactor.
AB  - This laboratory-scale study investigated the performance of a low-cost anaerobic
      digester for microalgae. Low (~2%) solids content wastewater-grown microalgal
      biomass (MB) was digested in an unmixed, accumulating-volume reactor (AVR) with
      solid and liquid separation that enabled a long solids retention time. AVRs (2 or
      20 L) were operated at 20  degrees C, 37  degrees C or ambient temperature (8-21 
      degrees C), and the influence of two pretreatments - low-temperature thermal (50
      57  degrees C) and freeze-thaw - on algal digestion were studied. The highest
      methane yield from untreated MB was in the 37  degrees C AVR with 225 L CH4 kg
      volatile solids (VS)(-1), compared with 180 L CH4 kg VS(-1)added in a
      conventional, 37  degrees C completely stirred tank reactor (CSTR), and 101 L CH4
      kg VS(-1)added in the 20  degrees C AVR. Freeze-thaw and low-temperature thermal
      pretreatments promoted protein hydrolysis and increased methane yields by 32-50%
      at 20  degrees C, compared with untreated MB. Pretreatments also increased the
      mineralisation of nitrogen (41-57%) and phosphorus (76-84%) during digestion. MB
      digestion at ambient temperature was comparable with digestion at 20  degrees C,
      until temperature dropped below 16  degrees C. 

PMID- 24726995
TI  - Methodology for profiling anti-androgen mixtures in river water using multiple
      passive samplers and bioassay-directed analyses.
AB  - The identification of endocrine disrupting chemicals in surface waters is
      challenging as they comprise a variety of structures which are often present at
      nanomolar concentrations and are temporally highly variable. Hence, a holistic
      passive sampling approach can be an efficient technique to overcome these
      limitations. In this study, a combination of 4 different passive samplers used
      for sampling polar (POCIS Apharm and POCIS Bpesticide) and apolar compounds (LDPE
      low density polyethylene membranes, and silicone strips) were used to profile
      anti-androgenic activity present in river water contaminated by a wastewater
      effluent. Extracts of passive samplers were analysed using HPLC fractionation in
      combination with an in vitro androgen receptor antagonist screen (YAS). Anti
      androgenic activity was detected in extracts from silicone strips and POCIS A/B
      at (mean +/- SD) 1.1 +/- 0.1 and 0.55 +/- 0.06 mg flutamide standard
      equivalents/sampler respectively, but was not detected in LDPE sampler extracts.
      POCIS samplers revealed higher selectivity for more polar anti-androgenic HPLC
      fractions compared with silicone strips. Over 31 contaminants were identified
      which showed inhibition of YAS activity and were potential anti-androgens, and
      these included fungicides, germicides, flame retardants and pharmaceuticals. This
      study reveals that passive sampling, using a combination of POCIS A and silicone
      samplers, is a promising tool for screening complex mixture of anti-androgenic
      contaminants present in surface waters, with the potential to identify new and
      emerging structures with endocrine disrupting activity. 

PMID- 24726996
TI  - Response surface modeling of Carbamazepine (CBZ) removal by Graphene-P25
      nanocomposites/UVA process using central composite design.
AB  - Graphene-P25 (Gr-P25) nanocomposites were synthesized by a simple microwave
      hydrothermal method. The nanocomposites with different graphene loading were
      evaluated for the degradation of an important pharmaceutical water pollutant,
      Carbamazepine (CBZ) under UVA irradiation in a batch reactor. Response surface
      methodology (RSM) was used to optimize three key independent operating
      parameters, namely Gr-P25 nanocomposites dose (X1), CBZ initial concentration
      (X2) and UV light intensity (X3), for photocatalytic degradation of CBZ. The
      central composite design (CCD) consisting of 20 experiments determined by 2(3)
      full factorial designs with six axial points and six center points was used to
      conduct experiments. The results showed that CBZ removal was significantly
      affected by the synergistic effect of linear term of Gr-P25 dose (X1) and UV
      intensity (X3). However, the quadratic terms of Gr-P25 (X1(2)) and UV intensity
      (X3(2)) had an antagonistic effect on CBZ removal. The obtained RSM model (R(2) =
      0.9206) showed a satisfactory correlation between experimental and predicted
      values of CBZ removal. The optimized conditions for achieving 100% CBZ removal
      with 5 min UVA irradiation were 25.14 mg/L, 167.68 ppb and 1.35 mW/cm(2) for Gr
      P25 dose, initial concentration of CBZ and UV intensity, respectively. 

PMID- 24726997
TI  - The origin of the PB1 segment of swine influenza A virus subtype H1N2 determines
      viral pathogenicity in mice.
AB  - Swine appear to be a key species in the generation of novel human influenza
      pandemics. Previous pandemic viruses are postulated to have evolved in swine by
      reassortment of avian, human, and swine influenza viruses. The human pandemic
      influenza viruses that emerged in 1957 and 1968 as well as swine viruses
      circulating since 1998 encode PB1 segments derived from avian influenza viruses.
      Here we investigate the possible role in viral replication and virulence of the
      PB1 gene segments present in two swine H1N2 influenza A viruses,
      A/swine/Sweden/1021/2009(H1N2) (sw 1021) and A/swine/Sweden/9706/2010(H1N2) (sw
      9706), where the sw 1021 virus has shown to be more pathogenic in mice. By using
      reverse genetics, we swapped the PB1 genes of these two viruses. Similar to the
      sw 9706 virus, chimeric sw 1021 virus carrying the sw 9706 PB1 gene was not
      virulent in mice. In contrast, replacement of the PB1 gene of the sw 9706 virus
      by that from sw 1021 virus resulted in increased pathogenicity. Our study
      demonstrated that differences in virulence of swine influenza virus subtype H1N2
      are attributed at least in part to the PB1 segment.

PMID- 24726999
TI  - Evaluation of partner collaboration to improve community-based mental health
      services for low-income minority children and their families.
AB  - This paper describes a mixed methods evaluation of partner agency collaboration
      within a system of care implemented from 2010 to 2012 in a historically
      underserved minority community in Houston, Texas. The first section describes the
      project and the framework for evaluating partner agency collaboration. The second
      section describes the evaluation methods and presents the baseline and follow-up
      results of the evaluation. The third section includes a discussion of the
      evaluation findings, the conclusion, and the lessons learned. 

PMID- 24726998
TI  - Disturbances in affective touch in hereditary sensory & autonomic neuropathy type
      III.
AB  - Hereditary sensory and autonomic neuropathy type III (HSAN III, Riley-Day
      syndrome, Familial Dysautomia) is characterised by elevated thermal thresholds
      and an indifference to pain. Using microelectrode recordings we recently showed
      that these patients possess no functional stretch-sensitive mechanoreceptors in
      their muscles (muscle spindles), a feature that may explain their lack of stretch
      reflexes and ataxic gait, yet patients have apparently normal low-threshold
      cutaneous mechanoreceptors. The density of C-fibres in the skin is markedly
      reduced in patients with HSAN III, but it is not known whether the C-tactile
      afferents, a distinct type of low-threshold C fibre present in hairy skin that is
      sensitive to gentle stroking and has been implicated in the coding of pleasant
      touch are specifically affected in HSAN III patients. We addressed the
      relationship between C-tactile afferent function and pleasant touch perception in
      15 patients with HSAN III and 15 age-matched control subjects. A soft make-up
      brush was used to apply stroking stimuli to the forearm and lateral aspect of the
      leg at five velocities: 0.3, 1, 3, 10 and 30 cm/s. As demonstrated previously,
      the control subjects rated the slowest and highest velocities as less pleasant
      than those applied at 1-10 cm/s, which fits with the optimal velocities for
      exciting C-tactile afferents. Conversely, for the patients, ratings of
      pleasantness did not fit the profile for C-tactile afferents. Patients either
      rated the higher velocities as more pleasant than the slow velocities, with the
      slowest velocities being rated unpleasant, or rated all velocities equally
      pleasant. We interpret this to reflect absent or reduced C-tactile afferent
      density in the skin of patients with HSAN III, who are likely using tactile cues
      (i.e. myelinated afferents) to rate pleasantness of stroking or are attributing
      pleasantness to this type of stimulus irrespective of velocity.

PMID- 24727001
TI  - Consultant who ran car export and property business through NHS computer is
      struck off.

PMID- 24727000
TI  - Cationic lipid guided short-hairpin RNA interference of annexin A2 attenuates
      tumor growth and metastasis in a mouse lung cancer stem cell model.
AB  - The role of side populations (SP) or cancer stem-like cells (CSC) in promoting
      the resistance phenotype presents a viable anticancer target. Human-derived H1650
      SP cells over-express annexin A2 (AnxA2) and SOX2, and are resistant to
      conventional cytotoxic chemotherapeutics. AnxA2 and SOX2 bind to proto-oncogenes,
      c-Myc and c-Src, and AnxA2 forms a functional heterotetramer with S100A10 to
      promote tumor motility. However, the combined role of AnxA2, S100A10 and SOX2 in
      promoting the resistant phenotype of SP cells has not been investigated. In the
      current studies, we examined for the first time a possible role of AnxA2 in
      regulating SA100A10 and SOX2 in promoting a resistant phenotype of lung tumors
      derived from H1650 SP cells. The resistance of H1650 SP cells to chemotherapy
      compared to H1650 MP cells was investigated by cell viability studies. A short
      hairpin RNA targeting AnxA2 (shAnxA2) was formulated in a liposomal (cationic
      ligand-guided, CLG) carrier and characterized for size, charge and entrapment and
      loading efficiencies; CLG carrier uptake by H1650 SP cells was demonstrated by
      fluorescence microscopy, and knockdown of AnxA2 confirmed by qRT-PCR and Western
      blot. Targeting of xenograft and orthotopic lung tumors was demonstrated with
      fluorescent (DiR) CLG carriers in mice. The therapeutic efficacy of CLG-AnxA2,
      compared to that of placebo, was investigated after 2 weeks of treatment in terms
      of tumor weights and tumor burden in vivo. Compared to mixed population cells,
      H1650 SP cells showed exponential resistance to docetaxel (15-fold), cisplatin
      (13-fold), 5-fluorouracil (31-fold), camptothecin (7-fold), and gemcitabine (16
      fold). CLG carriers were nanoparticulate (199nm) with a slight positive charge
      (21.82mV); CLG-shAnx2 was of similar size (217nm) with decreased charge
      (12.11mV), and entrapment and loading efficiencies of 97% and 6.13% respectively.
      Fluorescence microscopy showed high uptake of CLG-shAnxA2 in H1650 SP cells after
      2h resulting in a 6-fold reduction in AnxA2 mRNA expression and 92% decreased
      protein expression. Fluorescence imaging confirmed targeting of tumors and lungs
      by DiR-CLG carriers with sustained localization up to 4h in mice. CLG-shAnxA2
      treatment of mice significantly reduced the weights of lung tumors derived from
      H1650 SP cells and tumor burden was reduced to only 19% of controls. The loss in
      tumor weights in response to CLG-shAnxA2 was associated with a significant loss
      in the relative levels of AnxA2, SOX2, total beta-catenin and S100A10, both at
      the RNA and protein levels. These results suggest the intriguing possibility that
      AnxA2 may directly or indirectly regulate relative levels of beta-catenin,
      S100A10 and SOX2, and that the combination of these factors may contribute to the
      resistant phenotype of H1650 SP cells. Thus down-regulating AnxA2 using RNAi
      methods may provide a useful method for targeting cancer stem cells and help
      advance therapeutic efficacy against lung cancers.

PMID- 24727002
TI  - Current concepts of pheochromocytoma.
AB  - Pheochromocytoma (PCC), a rare neuroendocrine tumor, shows a prevalence ranging
      between 0.1% and 0.6% in individuals suffering from hypertension. To date, an
      increasing number of patients with hereditary forms or subclinical PCCs have been
      diagnosed. We reviewed the main controversies and the most recent updates,
      especially inheritance genetics and surgical management. According to the "rule
      of 10", in 1/10 patients with pheochromocytoma it is malignant, in 1/10 of cases
      the tumor is bilateral, in 1/10 extra-adrenal and in 1/10 familial. Surgical
      resection, the only curative treatment, carries a high risk of hypertensive
      crises due to massive catecholamine release. Alpha 1 blocker therapy, alone or in
      combination with beta blockers, calcium antagonists, and plasma volume expansion,
      is the most commonly used preoperative treatment protocol. Minimally invasive
      adrenalectomy (laparoscopic and retro-peritoneoscopic) allows earlier
      mobilization and recovery, reducing the risk of pulmonary infections and thromb
      oembolic complications, and is associated with lower morbidity and mortality
      rates than traditional surgery; it is currently considered the gold standard for
      the treatment of adrenal tumors <=6 cm in diameter and weighing < 100 g. Genetic
      testing will increasingly be the key factor in estimating the life-long risk for
      development of recurrent disease, contralateral disease or malignant
      dedifferentiation, thus influencing follow-up protocols.

PMID- 24727003
TI  - Combinatorial effects of amoxicillin and metronidazole on selected periodontal
      bacteria and whole plaque samples.
AB  - OBJECTIVE: The aim of the present study was to analyze in vitro the combinatorial
      effects of the antibiotic combination of amoxicillin plus metronidazole on
      subgingival bacterial isolates. DESIGN: Aggregatibacter (Actinobacillus)
      actinomycetemcomitans, Prevotella intermedia/nigrescens, Fusobacterium nucleatum
      and Eikenella corrodens from our strain collection and subgingival bacteria
      isolated from patients with periodontitis were tested for their susceptibility to
      amoxicillin and metronidazole using the Etest. The fractional inhibitory
      concentration index (FICI), which is commonly used to describe drug interactions,
      was calculated. RESULTS: Synergy, i.e. FICI values <= 0.5, between amoxicillin
      and metronidazole was shown for two A. actinomycetemcomitans (FICI: 0.3), two F.
      nucleatum (FICI: 0.3 and 0.5, respectively) and one E. corrodens (FICI: 0.4)
      isolates. Indifference, i.e. FIC indices of >0.5 but <=4, occurred for other
      isolates and the 14 P. intermedia/nigrescens strains tested. Microorganisms
      resistant to either amoxicillin or metronidazole were detected in all samples by
      Etest. CONCLUSION: Combinatorial effects occur between amoxicillin and
      metronidazole on some strains of A. actinomycetemcomitans, F. nucleatum and E.
      corrodens. Synergy was shown for a few strains only.

PMID- 24727005
TI  - Effect of experimental mouthrinses containing the combination of NaF and TiF4 on
      enamel erosive wear in vitro.
AB  - OBJECTIVE: This study analysed the anti-erosive effect of experimental solutions
      containing TiF4 and NaF. METHODS: Bovine enamel samples (n=15) were treated with:
      (1) commercial solution with SnCl2/NaF (Erosion Protection((r))); (2)
      experimental solution with 0.0815% TiF4; (3) 0.105% NaF; (4) 0.042% NaF + 0.049%
      TiF4; (5) 0.063% NaF + 0.036% TiF4 or (6) control. The samples were submitted to
      pH cycles and daily fluoride applications for seven days. The enamel wear was
      measured using a contact profilometer and analysed by ANOVA (p < 0.05). RESULTS:
      The best anti-erosive effect was found for experimental solution with 0.0815%
      TiF4 (99% reduction in enamel wear), followed by SnCl2/NaF (78%) and 0.049% TiF4
      + 0.042% NaF solution (41%). CONCLUSIONS: The experimental solution containing a
      specific combination of TiF4 + NaF has the ability to partially reduce enamel
      erosion.

PMID- 24727004
TI  - Quantitative analysis of survival of hypoglossal neurons in neonatally nerve
      injured rats: Correlation with milk intake.
AB  - INTRODUCTION: Tongue movement innervated by the hypoglossal (XII) nerve is
      essential for the survival of neonatal rats. The pups with bilateral XII nerve
      resection failed to suckle milk and did not survive, and the pups with unilateral
      XII nerve resection showed disturbed suckling capability and lower survival
      rates. The present study was performed to investigate the relation between
      neuronal population and milk intake of developing rats that had received various
      degrees of crush injuries to the unilateral XII nerve during the neonatal period.
      METHODS: The right XII nerve of postnatal day 1 (P1) pups was crushed and milk
      intake was estimated at 3 days and 6 days after the nerve injury. As nerve injury
      at the neonatal stage results in death of axotomized neurons, varying degrees of
      crushing was estimated by the number of survived motor neurons. RESULTS: In nerve
      crushed rats, the populations of XII motor neurons and amounts of milk intake
      were reduced in a varied manner. Statistically significant positive correlations
      were observed between increasing XII neuron survival and increasing milk intake
      at 3 (r=0.62) and 6 (r=0.71) days after the nerve injury. CONCLUSION: The results
      indicate that there is a strong relationship between the number of XII motor
      neurons and the amount of milk intake in neonatally XII nerve-injured rats.

PMID- 24727006
TI  - An unusual double supernumerary maxillary mesiodens in a Middle Iron Age skeleton
      from South Uist, Western Isles, Scotland.
AB  - OBJECTIVE: Bilaterally occurring and fully erupted mesiodens occur infrequently
      in the modern population and have been little documented from past populations.
      This research presents an unusual case of a double maxillary mesiodens in the
      permanent dentition occurring in skeletal remains dating to the Middle Iron Age
      (250-410 AD) from South Uist, Western Isles of Scotland. METHODS: Osteological
      analysis of an adult male included the inventory of teeth present/absent and
      analysis of dental pathologies (caries, calculus, periodontal disease, ante
      mortem tooth loss, periapical abscesses), developmental defects and orthodontic
      anomalies (enamel hypoplastic defects, malposition, rotation, crowding, agenesis
      and supernumerary teeth). RESULTS: An unusual expression of double, fully
      erupted, mesiodens in the anterior permanent maxillary dentition representing
      supernumerary central incisors exists. The complete eruption had contributed to
      anterior displacement of one central incisor alveolar socket similar to
      documented modern clinical cases. Shallow sockets also implied an associated
      stunted development of the original central maxillary incisor roots. Occlusal
      enamel wear indicated the mesiodens had been abraded during mastication.
      CONCLUSION: Current clinical data suggest there is a much higher tendency for
      single mesiodens to exist rather than double and examples often fail to fully
      erupt into the dentition. This relative rarity may account for the few previous
      reports of this dental anomaly from past human remains and especially of this
      date. The fully erupted double example from South Uist contributes to the known
      evidence for orthodontic anomalies in the past.

PMID- 24727007
TI  - Early caffeine exposure: transient and long-term consequences on brain
      excitability.
AB  - The influence of pre- and postnatal caffeine treatment on brain excitability
      during development and adulthood is reviewed. Pre- and postnatal exposure to
      caffeine induces sex- and age-specific long-term neurochemical alterations in the
      brain and the behavior of rodents. Because adenosine neuromodulation is closely
      related to the regulation of brain excitability the increased expression in
      adenosine receptor system due to neonatal caffeine treatment should cause
      transient and permanent changes in seizure susceptibility. So far, findings have
      been focused on primarily developmental changes of the brain adenosine modulatory
      system and have demonstrated that the alterations are not restricted to a single
      brain region. Neurobehavioral changes and the anticonvulsant effect of early
      caffeine exposure are dependent on the caffeine dose, developmental stage of
      exposure and age of testing. Although outcomes of caffeine treatment are still a
      matter of debate, our review raise questions concerning the impact of early
      caffeine treatment on regulation of seizure susceptibility during development and
      adulthood. 

PMID- 24727008
TI  - Understanding evaporation characteristics of a drop of distilled sulfur mustard
      (HD) chemical agent from stainless steel and aluminum substrates.
AB  - We report herein the evaporation rates and mechanism of a drop of distilled
      sulfur mustard (HD) agent from stainless steel and aluminum substrates. For
      systematic analysis, we used a laboratory-sized wind tunnel, thermal desorption
      (TD) connected to gas chromatograph/mass spectrometry (GC/MS) and drop shape
      analysis (DSA). We found that the evaporation rates of HD from stainless steel
      and aluminum increased with temperature. The rates were also linearly
      proportional to drop size. The time-dependent contact angle measurement showed
      that the evaporation of the drop of HD proceeded only by constant contact area
      mechanism from stainless steel surface. On the other hand, the evaporation of HD
      from aluminum proceeded by a combined mechanism of constant contact area mode and
      constant contact angle mode. Our experimental data sets and analysis could be
      used to predict vapor and contact hazard persistence of chemical warfare agents
      (CWAs) in the air and on exterior surfaces with chemical releases, which assists
      the military decision influencing personnel safety and decontamination of the
      site upon a chemical attack event. 

PMID- 24727009
TI  - Removal of acidic pharmaceuticals within a nitrifying recirculating biofilter.
AB  - The fate of pharmaceutically active compounds (PhACs) in wastewater treatment
      systems is an area of increasing concern. Little research has been done to
      understand this issue in rural or decentralized communities. The objective of
      this research was to examine the ability of a bench scale nitrifying
      recirculating biofilter (RBF) to remove four acidic PhACs: gemfibrozil, naproxen,
      ibuprofen and diclofenac from secondary treated municipal wastewater at
      concentrations of 20 and 200MUg/L. The average removals in this study were
      between 92 and 99% for ibuprofen, 89 and 99% for naproxen, 62 and 92% for
      gemfibrozil and 40 and 76% for diclofenac, which is consistent with literature.
      Ibuprofen and naproxen were largely removed through biological transformation;
      whereas gemfibrozil and diclofenac showed more variable removal, likely due to
      both biological transformation and sorption processes. PhAC removal in the RBFs
      was repeatable between trials, robust and responsive to system upsets, and the
      presence of PhACs as a single compound versus mixtures had no impact on PhAC
      removal efficiency. In summary, this study indicates that RBFs as a nitrifying
      stage of a multi-stage filtration process could be a viable technology for
      removal of some acidic pharmaceuticals in small onsite wastewater treatment
      facilities. 

PMID- 24727010
TI  - Removal of Pb(II) ions from aqueous solution using water hyacinth root by fixed
      bed column and ANN modeling.
AB  - Hyacinth root was used as a biosorbent for generating adsorption data in fixed
      bed glass column. The influence of different operating parameters like inlet
      Pb(II) ion concentration, liquid flow rate and bed height on the breakthrough
      curves and the performance of the column was studied. The result showed that the
      adsorption efficiency increased with increase in bed height and decreased with
      increase in inlet Pb(II) ion concentration and flow rate. Increasing the flow
      rate resulted in shorter time for bed saturation. The result showed that as the
      bed height increased the availability of more number of adsorption sites in the
      bed increased, hence the throughput volume of the aqueous solution also
      increased. The adsorption kinetics was analyzed using different models. It was
      observed that maximum adsorption capacity increased with increase in flow rate
      and initial Pb(II) ion concentration but decreased with increase in bed height.
      Applicability of artificial neural network (ANN) modeling for the prediction of
      Pb(II) ion removal was also reported by using multilayer perceptron with
      backpropagation, Levenberg-Marquardt and scaled conjugate algorithms and four
      different transfer functions in a hidden layer and a linear output transfer
      function. 

PMID- 24727011
TI  - Individual or synchronous biodegradation of di-n-butyl phthalate and phenol by
      Rhodococcus ruber strain DP-2.
AB  - The bacterial strain DP-2, identified as Rhodococcus ruber, is able to
      effectively degrade di-n-butyl phthalate (DBP) and phenol. Degradation kinetics
      of DBP and phenol at different initial concentrations revealed DBP and phenol
      degradation to fit modified first-order models. The half-life of DBP degradation
      ranged from 15.81 to 27.75h and phenol degradation from 14.52 to 45.52h under the
      initial concentrations of 600-1200mg/L. When strain DP-2 was cultured with a
      mixture of DBP (800mg/L) and phenol (700mg/L), DBP degradation rate was found to
      be only slightly influenced; however, phthalic acid (PA) accumulated, and phenol
      degradation was clearly inhibited during synchronous degradation. Transcriptional
      levels of degradation genes, phenol hydroxylase (pheu) and phthalate 3,4
      dioxygenase (pht), decreased significantly more during synchronous degradation
      than during individual degradation. Quantitative estimation of individual or
      synchronous degradation kinetics is essential to manage mixed hazardous compounds
      through biodegradation in industrial waste disposal. 

PMID- 24727012
TI  - Hexavalent chromium damages chamomile plants by alteration of antioxidants and
      its uptake is prevented by calcium.
AB  - Toxicity of low (3MUM) and high (60 and 120MUM) concentrations of hexavalent
      chromium/Cr(VI) in chamomile plants was studied. Fluorescence staining confirmed
      reduction of Cr(VI) to Cr(III). Cr was mainly accumulated in the roots with
      translocation factor <0.007. Notwithstanding this, both shoots and roots revealed
      increase in oxidative stress and depletion of glutathione, total thiols, ascorbic
      acid and activities of glutathione reductase and partially ascorbate peroxidase
      mainly at 120MUM Cr. Though some protective mechanisms were detected (elevation
      of nitric oxide, enhancement of GPX activity and increase in phenols and lignin),
      this was not sufficient to counteract the oxidative damage. Consequently, soluble
      proteins, tissue water content and biomass production were considerably depleted.
      Surprising increase in some mineral nutrients in roots (Ca, Fe, Zn and Cu) was
      also detected. Subsequent experiment confirmed that exogenous calcium suppressed
      oxidative symptoms and Cr uptake but growth of chamomile seedlings was not
      improved. Alteration of naturally present reductants could be a reason for
      Cr(III) signal detected using specific fluorescence reagent: in vitro assay
      confirmed disappearance of ascorbic acid in equimolar mixture with dichromate
      (>96% at pH 4 and 7) while such response of glutathione was substantially less
      visible. 

PMID- 24727013
TI  - Removal of cadmium ions from wastewater using innovative electronic waste-derived
      material.
AB  - Cadmium is a highly toxic heavy metal even at a trace level. In this study, a
      novel material derived from waste PCBs has been applied as an adsorbent to remove
      cadmium ions from aqueous solutions. The effects of various factors including
      contact time, initial cadmium ion concentration, pH and adsorbent dosage have
      been evaluated. The maximum uptake capacity of the newly derived material for
      cadmium ions has reached 2.1mmol/g at an initial pH 4. This value shows that this
      material can effectively remove cadmium ions from effluent. The equilibrium
      isotherm has been analyzed using several isotherm equations and is best described
      by the Redlich-Peterson model. Furthermore, different commercial adsorbent resins
      have been studied for comparison purposes. The results further confirm that this
      activated material is highly competitive with its commercial counterparts. 

PMID- 24727014
TI  - Comments on "Heavy metals and polycyclic aromatic hydrocarbons: pollution and
      ecological risk assessment in street dust of Tehran".

PMID- 24727015
TI  - Synthesis of magnetic activated carbon/alpha-Fe2O3 nanocomposite and its
      application in the removal of acid yellow 17 dye from water.
AB  - The adsorption of acid yellow 17 dye on activated carbon/alpha-Fe2O3
      nanocomposite prepared by simple pyrolytic method using iron(II) gluconate was
      investigated by batch technique. The composite was characterized by Fourier
      transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD), scanning
      electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDX),
      transmission electron microscopy (TEM), and vibrating sample magnetometry (VSM).
      The size of iron oxide nanoparticles formed from iron(II) gluconate precursor is
      in the range 5-17nm. The saturation magnetization (Ms), remanence (Mr) and
      coercivity (Hc) of the magnetic carbon nanocomposite is 5.6emu/g, 1.14emu/g and
      448Oe, respectively. The adsorption data are found to fit well with Langmuir and,
      fairly well with Freundlich and Tempkin isotherms at higher concentration of dye
      (40-100mg/L). Kinetics data indicate that the adsorption of dye follows pseudo
      second order kinetics model. 

PMID- 24727016
TI  - Environment-oriented low-cost porous mullite ceramic membrane supports fabricated
      from coal gangue and bauxite.
AB  - Porous mullite ceramic supports for filtration membrane were successfully
      fabricated via recycling of coal gangue and bauxite at sintering temperatures
      from 1100 to 1500 degrees C with corn starch as pore-forming agent. The dynamic
      sintering behaviors, phase evolution, shrinkage, porosity and pore size, gas
      permeation flux, microstructure and mechanical property were systematically
      studied. A unique volume-expansion stage was observed at increased temperatures
      from 1276 to 1481 degrees C caused by a mullitization-crystal-growth process.
      During this stage, open porosity increases and pore size distributions broaden,
      which result in a maximum of nitrogen gas flux at 1400 degrees C. The X-ray
      diffraction results reveal that secondary mullitization took place from 1100
      degrees C and the major phase is mullite with a content of ~84.7wt.% at 1400
      degrees C. SEM images show that the as-fabricated mullite supports have a porous
      microstructure composed of sintered glassy particles embedded with inter-locked
      mullite crystals, which grew gradually with increasing temperature from rod-like
      into blocky-like morphologies. To obtain mullite membrane supports with
      sufficient porosity and acceptable mechanical strength, the relationship between
      porosity and mechanical strength was investigated, which was fitted using a
      parabolic equation. 

PMID- 24727017
TI  - Development of high efficiency silica coated beta-cyclodextrin polymeric
      adsorbent for the removal of emerging contaminants of concern from water.
AB  - This article reports the removal of several emerging contaminants (ECs) from
      water using novel adsorbent comprising of beta-cyclodextrin (beta-CD) coated on
      silica. Fourteen different adsorbents were synthesized under different
      experimental conditions using two different crosslinking agents (hexamethylene
      diisocyanate (HMDI) and epichlorohydrin (EPI)) and co-polymers (glycidoxypropyl
      trimethoxysilane (GPTS) and aminopropyl triethoxysilane (APTES). The adsorption
      capacities of the synthesized adsorbents were initially evaluated using 17beta
      estradiol, perfluorooctanoic acid (PFOA), and bisphenol-A (BPA) as adsorbates.
      The adsorbent prepared by using HMDI as crosslinking agent with DMSO as solvent
      was observed to perform the best, and removed more than 90% of 17beta-estradiol,
      PFOA, and BPA. Furthermore, the beta-CD loading on the ECs removal was studied
      which showed that the adsorbate removal increases with increase in loading of
      beta-CD on the substrate. The best adsorbent was resynthesized in seven batches
      and its performance was reproducible for the removal of ten steroid hormones. The
      adsorbent showed very good regeneration potential for four successive adsorption
      regeneration cycles to remove steroid hormones and PFOA. A plausible mechanism of
      adsorption is proposed. The synthesized best adsorbent is characterized using
      FTIR, HR-TEM, TGA and nitrogen adsorption analysis. The TGA results showed that
      the adsorbent has thermal stability of upto 300 degrees C. 

PMID- 24727019
TI  - Host plant-specific remodeling of midgut physiology in the generalist insect
      herbivore Trichoplusia ni.
AB  - Species diversity in terrestrial ecosystems is influenced by plant defense
      compounds that alter the behavior, physiology, and host preference of insect
      herbivores. Although it is established that insects evolved the ability to
      detoxify specific allelochemicals, the mechanisms by which polyphagous insects
      cope with toxic compounds in diverse host plants are not well understood. Here,
      we used defended and non-defended plant genotypes to study how variation in
      chemical defense affects midgut responses of the lepidopteran herbivore
      Trichoplusia ni, which is a pest of a wide variety of native and cultivated
      plants. The genome-wide midgut transcriptional response of T. ni larvae to
      glucosinolate-based defenses in the crucifer Arabidopsis thaliana was
      characterized by strong induction of genes encoding Phase I and II detoxification
      enzymes. In contrast, the response of T. ni to proteinase inhibitors and other
      jasmonate-regulated defenses in tomato (Solanum lycopersicum) was dominated by
      changes in the expression of digestive enzymes and, strikingly, concomitant
      repression of transcripts encoding detoxification enzymes. Unbiased proteomic
      analyses of T. ni feces demonstrated that tomato defenses remodel the complement
      of T.ni digestive enzymes, which was associated with increased amounts of serine
      proteases and decreased lipase protein abundance upon encountering tomato defense
      chemistry. These collective results indicate that T. ni adjusts its gut
      physiology to the presence of host plant-specific chemical defenses, and further
      suggest that plants may exploit this digestive flexibility as a defensive
      strategy to suppress the production of enzymes that detoxify allelochemicals. 

PMID- 24727018
TI  - Distribution and phytoavailability of heavy metal chemical fractions in
      artificial soil on rock cut slopes alongside railways.
AB  - Artificial soil is often sprayed onto cut slopes alongside railroad tracks to
      promote revegetation. This study evaluated the heavy metal content and the
      distribution of heavy metal chemical fractions in the soil, as well as the uptake
      of heavy metals by plants. The soil at four sites was determined to be
      considerably contaminated with Cd and Pb. The concentrations of Cd and Pb
      increased with the length of time the railway had been in use and decreased
      further away from the railway tracks. Pb primarily existed in reducible form but
      as residual fractions, whereas Cd was predominantly in exchangeable form. A
      correlation analysis indicated that pH, organic matter, and total phosphorus
      levels were important factors affecting the distribution of the heavy metal
      chemical fractions. The amounts of exchangeable Pb and Cd in the soil were highly
      correlated with their amounts in the plants sampled, indicating that the
      exchangeable fraction is a better indication of heavy metal phytoavailability
      than the total amount of heavy metals in the soil. Bioaccumulation and
      translocation factors indicated that Indigofera amblyantha had moderate tolerance
      and bioaccumulation capability for Pb, as did Leucaena leucocephala for Cd. These
      two plant species can serve as ideal slope remediation plants. 

PMID- 24727020
TI  - Bacterial origin of a diverse family of UDP-glycosyltransferase genes in the
      Tetranychus urticae genome.
AB  - UDP-glycosyltransferases (UGTs) catalyze the conjugation of a variety of small
      lipophilic molecules with uridine diphosphate (UDP) sugars, altering them into
      more water-soluble metabolites. Thereby, UGTs play an important role in the
      detoxification of xenobiotics and in the regulation of endobiotics. Recently, the
      genome sequence was reported for the two-spotted spider mite, Tetranychus
      urticae, a polyphagous herbivore damaging a number of agricultural crops.
      Although various gene families implicated in xenobiotic metabolism have been
      documented in T. urticae, UGTs so far have not. We identified 80 UGT genes in the
      T. urticae genome, the largest number of UGT genes in a metazoan species reported
      so far. Phylogenetic analysis revealed that lineage-specific gene expansions
      increased the diversity of the T. urticae UGT repertoire. Genomic distribution,
      intron-exon structure and structural motifs in the T. urticae UGTs were also
      described. In addition, expression profiling after host-plant shifts and in
      acaricide resistant lines supported an important role for UGT genes in xenobiotic
      metabolism. Expanded searches of UGTs in other arachnid species (Subphylum
      Chelicerata), including a spider, a scorpion, two ticks and two predatory mites,
      unexpectedly revealed the complete absence of UGT genes. However, a centipede
      (Subphylum Myriapoda) and a water flea and a crayfish (Subphylum Crustacea)
      contain UGT genes in their genomes similar to insect UGTs, suggesting that the
      UGT gene family might have been lost early in the Chelicerata lineage and
      subsequently re-gained in the tetranychid mites. Sequence similarity of T.
      urticae UGTs and bacterial UGTs and their phylogenetic reconstruction suggest
      that spider mites acquired UGT genes from bacteria by horizontal gene transfer.
      Our findings show a unique evolutionary history of the T. urticae UGT gene family
      among other arthropods and provide important clues to its functions in relation
      to detoxification and thereby host adaptation. 

PMID- 24727023
TI  - At the crossroads of physiology and ecology: food supply and the timing of avian
      reproduction.
AB  - This article is part of a Special Issue "Energy Balance". The decision of when to
      breed is crucial to the reproductive success and fitness of seasonally breeding
      birds. The availability of food for adults prior to breeding has long been
      thought to play a critical role in timing the initiation of seasonal reproductive
      events, in particular laying. However, unequivocal evidence for such a role
      remains limited and the physiological mechanisms by which an increase in food
      availability results in seasonal activation of the reproductive system are
      largely speculative. This lack of mechanistic information partly reflects a lack
      of integration of ecological and physiological approaches to study seasonal
      reproduction. Indeed, most work pertaining to the role of food availability for
      adults on the timing of avian reproduction has been ecological and has focused
      almost exclusively on female traits associated with reproductive timing (e.g.,
      lay date and clutch size). By contrast, most work on the physiological bases of
      the relationship between food availability and the timing of reproduction has
      investigated male traits associated with reproductive development (e.g.,
      reproductive hormones and gonadal development). To advance our understanding of
      these topics, we review the role of proximate factors including food
      availability, social factors, and ambient temperature in the control of breeding
      decisions, and discuss the role of three potential candidates (leptin,
      glucocorticoids, and GnIH-neuropeptide Y) that may mediate the effects of food
      availability on these decisions. We emphasize that future progress in this area
      is heavily contingent upon the use of physiology-based approaches and their
      integration into current ecological frameworks.

PMID- 24727021
TI  - Copper metabolism domain-containing 1 represses genes that promote inflammation
      and protects mice from colitis and colitis-associated cancer.
AB  - BACKGROUND & AIMS: Activation of the transcription factor nuclear factor-kappaB
      (NF-kappaB) has been associated with the development of inflammatory bowel
      disease (IBD). Copper metabolism MURR1 domain containing 1 (COMMD1), a regulator
      of various transport pathways, has been shown to limit NF-kappaB activation. We
      investigated the roles of COMMD1 in the pathogenesis of colitis in mice and IBD
      in human beings. METHODS: We created mice with a specific disruption of Commd1 in
      myeloid cells (Mye-knockout [K/O] mice); we analyzed immune cell populations and
      functions and expression of genes regulated by NF-kappaB. Sepsis was induced in
      Mye-K/O and wild-type mice by cecal ligation and puncture or intraperitoneal
      injection of lipopolysaccharide (LPS), colitis was induced by administration of
      dextran sodium sulfate, and colitis-associated cancer was induced by
      administration of dextran sodium sulfate and azoxymethane. We measured levels of
      COMMD1 messenger RNA in colon biopsy specimens from 29 patients with IBD and 16
      patients without (controls), and validated findings in an independent cohort (17
      patients with IBD and 22 controls). We searched for polymorphisms in or near
      COMMD1 that were associated with IBD using data from the International IBD
      Genetics Consortium and performed quantitative trait locus analysis. RESULTS: In
      comparing gene expression patterns between myeloid cells from Mye-K/O and wild
      type mice, we found that COMMD1 represses expression of genes induced by LPS. Mye
      K/O mice had more intense inflammatory responses to LPS and developed more severe
      sepsis and colitis, with greater mortality. More Mye-K/O mice with colitis
      developed colon dysplasia and tumors than wild-type mice. We observed a reduced
      expression of COMMD1 in colon biopsy specimens and circulating leukocytes from
      patients with IBD. We associated single-nucleotide variants near COMMD1 with
      reduced expression of the gene and linked them with increased risk for ulcerative
      colitis. CONCLUSIONS: Expression of COMMD1 by myeloid cells has anti-inflammatory
      effects. Reduced expression or function of COMMD1 could be involved in the
      pathogenesis of IBD.

PMID- 24727022
TI  - The combination of MK-5172, peginterferon, and ribavirin is effective in
      treatment-naive patients with hepatitis C virus genotype 1 infection without
      cirrhosis.
AB  - BACKGROUND & AIMS: MK-5172 is an inhibitor of the hepatitis C virus (HCV)
      nonstructural protein 3/4A protease; MK-5172 is taken once daily and has a higher
      potency and barrier to resistance than licensed protease inhibitors. We
      investigated the efficacy and tolerability of MK-5172 with peginterferon and
      ribavirin (PR) in treatment-naive patients with chronic HCV genotype 1 infection
      without cirrhosis. METHODS: We performed a multicenter, double-blind, randomized,
      active-controlled, dose-ranging, response-guided therapy study. A total of 332
      patients received MK-5172 (100, 200, 400, or 800 mg) once daily for 12 weeks in
      combination with PR. Patients in the MK-5172 groups received PR for an additional
      12 or 36 weeks, based on response at week 4. Patients in the control group (n =
      66) received a combination of boceprevir and PR, dosed in accordance with
      boceprevir's US product circular. RESULTS: At 24 weeks after the end of therapy,
      sustained virologic responses were achieved in 89%, 93%, 91%, and 86% of the
      patients in the groups given the combination of PR and MK-5172 (100, 200, 400, or
      800 mg), respectively, vs 61% of controls. In the MK-5172 group receiving 100 mg,
      91% of patients had undetectable levels of HCV RNA at week 4 and qualified for
      the short duration of therapy. The combination of MK-5172 and PR generally was
      well tolerated. Transient increases in transaminase levels were noted in the MK
      5172 groups given 400 and 800 mg, at higher frequencies than in the MK-5172
      groups given 100 or 200 mg, or control groups. CONCLUSIONS: Once-daily MK-5172
      (100 mg) with PR for 24 or 48 weeks was highly effective and well tolerated among
      treatment-naive patients with HCV genotype 1 infection without cirrhosis. Studies
      are underway to evaluate interferon-free MK-5172-based regimens.
      ClinicalTrials.gov number: NCT01353911.

PMID- 24727024
TI  - Exposure to perceived male rivals raises men's testosterone on fertile relative
      to nonfertile days of their partner's ovulatory cycle.
AB  - The challenge hypothesis posits that male testosterone levels increase in the
      presence of fertile females to facilitate mating and increase further in the
      presence of male rivals to facilitate male-male competition. This hypothesis has
      been supported in a number of nonhuman animal species. We conducted an experiment
      to test the challenge hypothesis in men. Thirty-four men were randomly assigned
      to view high-competitive or low-competitive male rivals at high and low fertility
      within their partner's ovulatory cycle (confirmed by luteinizing hormone tests).
      Testosterone was measured upon arrival to the lab and before and after the
      manipulation. Based on the challenge hypothesis, we predicted that a) men's
      baseline testosterone would be higher at high relative to low fertility within
      their partner's cycle, and b) men's testosterone would be higher in response to
      high-competitive rivals, but not in response to low-competitive rivals, at high
      relative to low fertility within their partner's cycle. Contrary to the first
      prediction, men's baseline testosterone levels did not differ across high and low
      fertility. However, consistent with the second prediction, men exposed to high
      competitive rivals showed significantly higher post-test testosterone levels at
      high relative to low fertility, controlling for pre-test testosterone levels. Men
      exposed to low-competitive rivals showed no such pattern (though the fertility by
      competition condition interaction fell short of statistical significance). This
      preliminary support for the challenge hypothesis in men builds on a growing
      empirical literature suggesting that men possess mating adaptations sensitive to
      fertility cues emitted by their female partners. 

PMID- 24727026
TI  - Transcriptional regulation of de novo biosynthesis of cyanogenic glucosides
      throughout the life-cycle of the burnet moth Zygaena filipendulae (Lepidoptera).
AB  - The six-spotted burnet moth Zygaena filipendulae (Lepidoptera) utilize the two
      cyanogenic glucosides (CNglcs) linamarin and lotaustralin as deterrents against
      predators throughout the entire life cycle. CNglcs can be hydrolyzed and
      bioactivated by beta-glucosidases, resulting in the release of toxic hydrogen
      cyanide. CNglcs are retained through metamorphosis, probably involved in mating
      communication, and transferred during mating from the male to the female as a
      nuptial gift. CNglcs can be biosynthesized de novo by Z. filipendulae larvae, but
      may also be sequestered from their food plant Lotus corniculatus (Fabaceae).
      These two strategies are tightly linked and adjusted according to the CNglc
      content and composition of the food plant in order to balance CNglc homeostasis
      in the larva. In this study, the amounts of CNglcs and transcript levels of the
      biosynthetic genes were monitored in all life-stages and tissues of Z.
      filipendulae. During pupation, transcription of the biosynthetic genes is turned
      off and the CNglc content slowly declines. In females but not males,
      transcription of the biosynthetic genes is re-activated at the end of pupation.
      Eggs and embryos do not biosynthesize CNglcs de novo, but are endowed with CNglcs
      following eclosion of the female. Similarly to larvae, de novo biosynthesis in
      female adults takes place in the integument from which CNglcs are then
      transported to other organs. This study demonstrates that Z. filipendulae has
      evolved the ability to adjust the production of CNglcs throughout its life-cycle
      for optimal utilization in defense and possibly other metabolic functions, while
      at the same time avoiding intoxication. 

PMID- 24727025
TI  - Postintegration stability of the silkworm piggyBac transposon.
AB  - The piggyBac transposon is the most widely used vector for generating transgenic
      silkworms. The silkworm genome contains multiple piggyBac-like sequences that
      might influence the genetic stability of transgenic lines. To investigate the
      postintegration stability of piggyBac in silkworms, we used random insertion of
      the piggyBac [3 * p3 EGFP afm] vector to generate a W chromosome-linked
      transgenic silkworm, named W-T. Results of Southern blot and inverse PCR revealed
      the insertion of a single copy in the W chromosome of W-T at a standard TTAA
      insertion site. Investigation of 11 successive generations showed that all W-T
      females were EGFP positive and all males were EGFP negative; PCR revealed that
      the insertion site was unchanged in W-T offspring. These results suggested that
      endogenous piggyBac-like elements did not affect the stability of piggyBac
      inserted into the silkworm genome. 

PMID- 24727027
TI  - Functional analysis of the glycogen binding subunit CG9238/Gbs-70E of protein
      phosphatase 1 in Drosophila melanogaster.
AB  - The product of the CG9238 gene that we termed glycogen binding subunit 70E (Gbs
      70E) was characterized by biochemical and molecular genetics methods. The
      interaction between Gbs-70E and all catalytic subunits of protein phosphatase 1
      (Pp1-87B, Pp1-9C, Pp1-96A and Pp1-13C) of Drosophila melanogaster was confirmed
      by pairwise yeast two-hybrid tests, co-immunoprecipitation and pull down
      experiments. The binding of Gbs-70E to glycogen was demonstrated by sedimentation
      analysis. With RT-PCR we found that the mRNAs coding for the longer Gbs-70E PB/PC
      protein were expressed in all developmental stages of the fruit flies while the
      mRNA for the shorter Gbs-70E PA was restricted to the eggs and the ovaries of the
      adult females. The development specific expression of the shorter splice variant
      was not conserved in different Drosophila species. The expression level of the
      gene was manipulated by P-element insertions and gene deletion to analyze the
      functions of the gene product. A small or moderate reduction in the gene
      expression resulted in no significant changes, however, a deletion mutant
      expressing very low level of the transcript lived shorter and exhibited reduced
      glycogen content in the imagos. In addition, the gene deletion decreased the
      fertility of the fruit flies. Our results prove that Gbs-70E functions as the
      glycogen binding subunit of protein phosphatase 1 that regulates glycogen content
      and plays a role in the development of eggs in D. melanogaster. 

PMID- 24727029
TI  - Two decades of proteomics in Latin America: a personal view.
AB  - Proteomics is the charming young daughter of classical protein chemistry. It was
      conceived in 1975, year of invention of the first proteomic technique, the
      procedure to separate Escherichia coli and mouse tissue proteins in a two
      dimensional polyacrylamide gel. Pregnancy, however, lasted for over 10years and
      deliverance occurred together with sister protein mass spectrometry. Jointly, the
      two techniques changed protein chemistry moving it from the study of single
      molecular entities to whole cell extracts and fluids. This review does not
      propose to report state-of-the art in proteomics in Latin America but rather to
      describe its development with emphasis on leading Brazil and Cuba as well as
      discuss proteomic research in these and other countries exposing the history and
      stories of researchers and selected laboratories that contributed to its
      establishment and development in the last 20years. BIOLOGICAL SIGNIFICANCE: This
      manuscript accounts for the fact that proteomics was present in Latin America
      since its birth. However, because the political and the economic situation in the
      region during the eighties and nineties were not favorable for science expansion,
      its beginning was shy. This changed at the dawn of the 21st century in such a way
      that a Latin American country, Brazil, became number 10 in manuscripts published
      in high impact journals as the Journal of Proteomics and Proteomics in 2012/2013.
      Interestingly, actual prevailing research themes come from centenary protein
      areas of study - e.g. neglected diseases - that quickly migrated from classical
      protein chemistry to proteomics, especially human parasites and snake, scorpion
      and spider venoms. This article is part of a Special Issue entitled: "20years of
      Proteomics" in memory of Viatliano Pallini" Guest Editors: Luca Bini, Juan J.
      Calvete, Natacha Turck, Denis Hochstrasser and Jean-Charles Sanchez.

PMID- 24727028
TI  - Fli1 acts downstream of Etv2 to govern cell survival and vascular homeostasis via
      positive autoregulation.
AB  - RATIONALE: Cardiovascular health depends on proper development and integrity of
      blood vessels. Ets variant 2 (Etv2), a member of the E26 transforming-specific
      family of transcription factors, is essential to initiate a transcriptional
      program leading to vascular morphogenesis in early mouse embryos. However,
      endothelial expression of the Etv2 gene ceases at midgestation; therefore,
      vascular development past this stage must continue independent of Etv2.
      OBJECTIVE: To identify molecular mechanisms underlying transcriptional regulation
      of vascular morphogenesis and homeostasis in the absence of Etv2. METHODS AND
      RESULTS: Using loss- and gain-of-function strategies and a series of molecular
      techniques, we identify Friend leukemia integration 1 (Fli1), another E26
      transforming-specific family transcription factor, as a downstream target of
      Etv2. We demonstrate that Etv2 binds to conserved Ets-binding sites within the
      promoter region of the Fli1 gene and governs Fli1 expression. Importantly, in the
      absence of Etv2 at midgestation, binding of Etv2 at Ets-binding sites in the Fli1
      promoter is replaced by Fli1 protein itself, sustaining expression of Fli1 as
      well as selective Etv2-regulated endothelial genes to promote endothelial cell
      survival and vascular integrity. Consistent with this, we report that Fli1 binds
      to the conserved Ets-binding sites within promoter and enhancer regions of other
      Etv2-regulated endothelial genes, including Tie2, to control their expression at
      and beyond midgestation. CONCLUSIONS: We have identified a novel positive feed
      forward regulatory loop in which Etv2 activates expression of genes involved in
      vasculogenesis, including Fli1. Once the program is activated in early embryos,
      Fli1 then takes over to sustain the process in the absence of Etv2.

PMID- 24727030
TI  - Effects of peritoneal ropivacaine nebulization for pain control after
      laparoscopic gynecologic surgery.
AB  - STUDY OBJECTIVE: To evaluate the effects of peritoneal cold nebulization of
      ropivacaine on pain control after gynecologic laparoscopy. DESIGN: Evidence
      obtained from a properly designed, randomized, double-blind, placebo-controlled
      trial (Canadian Task Force classification I). SETTING: Tertiary care center.
      PATIENTS: One hundred thirty-five women with American Society of
      Anesthesiologists disease classified as ASA I-III who were scheduled to undergo
      operative laparoscopy. INTERVENTION: Patients were randomized to receive either
      nebulization of 30 mg ropivacaine before surgery (preoperative group),
      nebulization of 30 mg ropivacaine after surgery (postoperative group),
      instillation of 100 mg ropivacaine before surgery (instillation group), or
      instillation of saline solution (control group). Nebulization was performed using
      the Aeroneb Pro device. MEASUREMENT AND MAIN RESULTS: Pain scores, morphine
      consumption, and ambulation time were collected in the post-anesthesia care unit
      and at 4, 6, and 24 hours postoperatively. One hundred eighteen patients
      completed the study. Patients in the preoperative group reported lower pain
      Numeric Ranking Scale values compared with those in the control group (net
      difference 2 points; 95% confidence interval [CI], 0.3-3.1 at 4 hours, 1-3 at 6
      hours, and 0.7-3 at 24 hours; p = .01) Patients in the preoperative group
      consumed significantly less morphine than did those in the control group (net
      difference 7 mg; 95% CI, 0.7-13; p = .02). More patients who received
      nebulization walked without assistance within 12 hours after awakening than did
      those in the instillation and control groups (net difference 15%; 95% CI, 6%-24%;
      p = .001). CONCLUSIONS: Cold nebulization of ropivacaine before surgery reduced
      postoperative pain and morphine consumption and was associated with earlier
      walking without assistance.

PMID- 24727031
TI  - Effect of surgery for endometrioma on ovarian function: a different point of
      view.
AB  - Recent evidence in the literature suggests that surgical excision of the
      endometrioma wall may reduce ovarian reserve, which may have a negative effect on
      subsequent reproductive function. However, because of inconsistent results and
      methodologic flaws of anti-mullerian hormone (AMH) as a marker of ovarian
      reserve, antral follicle count may be a more accurate noninvasive marker than
      AMH. Evaluating ovarian reserve using antral follicle count rather than AMH may
      yield different conclusions insofar as postsurgical damage to the ovary. Surgery
      should be performed only by experienced surgeons, and the stripping technique
      currently is still the only one supported by strong scientific evidence. The dual
      function of surgery, that is, to improve fertility and reduce pain, cannot be
      minimized or undervalued. 

PMID- 24727032
TI  - Differentiating between septate and bicornuate uterus: bi-dimensional and 3
      dimensional power Doppler findings.
AB  - STUDY OBJECTIVE: To assess if any difference could be found in uterine
      vascularization between septate and bicornuate uterus. DESIGN: Pilot study
      (Canadian Task Force classification II-2). SETTING: University hospital
      infertility clinic. PATIENTS: One hundred nine women with complete duplication of
      the uterine cavity. All had already received the final diagnosis of the type of
      uterine malformation, either septate uterus or bicornuate uterus, via diagnostic
      hysteroscopy and laparoscopy. Another group of 10 patients with uterine anomalies
      and affected by ovarian mass were also evaluated via intravenous contrast medium
      enhanced ultrasound examination. INTERVENTIONS: Patients were evaluated using 2
      dimensional and 3-dimensional power Doppler imaging of the uterus. MEASUREMENTS
      AND MAIN RESULTS: Seventy-three patients with septate uterus, with or without
      cervical and vaginal duplication, and 36 patients with bicornuate uterus were
      selected for inclusion in the study. Irregular vascular networks were detected
      between the 2 hemicavities in the patients with septate uterus. All bicornuate
      uteri showed a peculiar vascular network between the 2 hemicavities: the main
      recognizable vessels formed a network depicting the Greek letter gamma at the
      level of the uterine midline. Detection of the gamma sign can be used to
      differentiate septate from bicornuate uterus. This finding was also confirmed in
      patients who underwent intravenous contrast medium-enhanced ultrasound
      examination. CONCLUSIONS: power Doppler provides a new and uninvasive tool for
      differentiation of septate from bicornuate uterus.

PMID- 24727033
TI  - The role of matricellular proteins in glaucoma.
AB  - Glaucoma is an optic neuropathy affecting approximately 60million people
      worldwide and is the second most common cause of irreversible blindness. Elevated
      intraocular pressure (IOP) is the main risk factor for developing glaucoma and is
      caused by impaired aqueous humor drainage through the trabecular meshwork (TM)
      and Schlemm's canal (SC). In primary open angle glaucoma (POAG), this elevation
      in IOP in turn leads to deformation at the optic nerve head (ONH) specifically at
      the lamina cribrosa (LC) region where there is also a deposition of extracellular
      matrix (ECM) molecules such as collagen and fibronectin. Matricellular proteins
      are non-structural secreted glycoproteins that help cells communicate with their
      surrounding ECM. This family of proteins includes connective tissue growth factor
      (CTGF), also known as CCN2, thrombospondins (TSPs), secreted protein acidic and
      rich in cysteine (SPARC), periostin, osteonectin, and Tenascin-C and -X and other
      ECM proteins. All members appear to play a role in fibrosis and increased ECM
      deposition. Most are widely expressed in tissues particularly in the TM and ONH
      and deficiency of TSP1 and SPARC have been shown to lower IOP in mouse models of
      glaucoma through enhanced outflow facility. The role of these proteins in
      glaucoma is emerging as some have an association with the pathophysiology of the
      TM and LC regions and might therefore be potential targets for therapeutic
      intervention in glaucoma. 

PMID- 24727034
TI  - Modulated growth, stability and interactions of liquid-like coacervate assemblies
      of elastin.
AB  - Elastin self-assembles from monomers into polymer networks that display
      elasticity and resilience. The first major step in assembly is a liquid-liquid
      phase separation known as coacervation. This process represents a continuum of
      stages from initial phase separation to early growth of droplets by coalescence
      and later "maturation" leading to fiber formation. Assembly of tropoelastin-rich
      globules is on pathway for fiber formation in vivo. However, little is known
      about these intermediates beyond their size distribution. Here we investigate the
      contribution of sequence and structural motifs from full-length tropoelastin and
      a set of elastin-like polypeptides to the maturation of coacervate assemblies,
      observing their growth, stability and interaction behavior, and polypeptide
      alignment within matured globules. We conclude that maturation is driven by
      surface properties, leading to stabilization of the interface between the
      hydrophobic interior and aqueous solvent, potentially through structural motifs,
      and discuss implications for droplet interactions in fiber formation. 

PMID- 24727036
TI  - A wintertime investigation of atmospheric deposition of metals and polycyclic
      aromatic hydrocarbons in the Athabasca Oil Sands Region, Canada.
AB  - With planned expansion of oil sands facilities, there is interest in being able
      to characterize the magnitude and extent of deposition of metals and polycyclic
      aromatic hydrocarbons (PAH) in the Athabasca Oil Sands Region (AOSR) of Alberta.
      A study was undertaken using a bulk collection system to characterize wintertime
      atmospheric deposition of selected inorganic and organic contaminants in the
      AOSR. The study was carried out from January to March 2012 at two sampling sites
      near (within a 20 km circle of oil sands development) and two sampling sites
      distant (>45 km) to oil sands development. Triplicate bulk samplers were used to
      estimate precision of the method at one distant site. Monthly deposition samples
      were analyzed for 36 metals, ultra-low mercury, and 25 PAHs (including alkylated,
      and parent PAH). At the two sites located within 20 km of oil sands development,
      3-month wintertime integrated deposition for some priority metals, alkylated and
      parent PAH were higher compared to distant sites. Deposition fluxes of metals and
      PAH were compared to other available bulk deposition studies worldwide. Median
      bulk measurement uncertainties of metals and both PAH classes were 26% and within
      +/-15%, respectively suggesting that the bulk sampling method is a potential
      alternative for obtaining future direct measures of wintertime metals and PAH
      deposition at locations without access to power in the AOSR.

PMID- 24727035
TI  - Reprint of: A rapid increase in macrophage-derived versican and hyaluronan in
      infectious lung disease.
AB  - The goals of this study were to characterize the changes in chondroitin sulfate
      proteoglycans and hyaluronan in lungs in acute response to gram-negative
      bacterial infection and to identify cellular components responsible for these
      changes. Mice were treated with intratracheal (IT) live Escherichia coli, E. coli
      lipopolysaccharide (LPS), or PBS. Both E. coli and LPS caused rapid selective
      increases in mRNA expression of versican and hyaluronan synthase (Has) isoforms 1
      and 2 associated with increased immunohistochemical and histochemical staining
      for versican and hyaluronan in the lungs. Versican was associated with a subset
      of alveolar macrophages. To examine whether macrophages contribute to versican
      and hyaluronan accumulation, in vitro studies with primary cultures of bone
      marrow-derived and alveolar macrophages were performed. Unstimulated macrophages
      expressed very low levels of versican and hyaluronan synthase mRNA, with no
      detectible versican protein or hyaluronan product. Stimulation with LPS caused
      rapid increases in versican mRNA and protein, a rapid increase in Has1 mRNA, and
      concomitant inhibition of hyaluronidases 1 and 2, the major hyaluronan degrading
      enzymes. Hyaluronan could be detected following chloroquine pre-treatment,
      indicating rapid turnover and degradation of hyaluronan by macrophages. In
      addition, the effects of LPS, the M1 macrophage classical activation agonist,
      were compared to those of IL-4/IL-13 or IL-10, the M2a and M2c alternative
      activation agonists, respectively. Versican and Has1 increased only in response
      to M1 activation. Finally, the up-regulation of versican and Has1 in the whole
      lungs of wild-type mice following IT LPS was completely abrogated in TLR-4(-/-)
      mice. These findings suggest that versican and hyaluronan synthesis may play an
      important role in the innate immune response to gram-negative lung infection. 

PMID- 24727037
TI  - Simulation of the fate of selected pharmaceuticals and personal care products in
      a highly impacted reach of a Canadian watershed.
AB  - Municipal wastewater treatment plants (WWTPs) dispose of numerous trace organic
      contaminants in the receiving waters that can impact biological function in
      aquatic organisms. However, the complex nature of WWTP effluent mixtures and a
      wide variety of potential mechanisms that can alter physiological and
      reproductive development of aquatic organisms make it difficult to assess the
      linkages and severity of the effects associated with trace organic contaminants.
      This paper describes a surface water quality modeling exercise that was performed
      to understand the relevant contaminant fate and transport processes necessary to
      accurately predict the concentrations of trace organic compounds present in the
      aquatic environment. The target compounds modeled include a known antiandrogenic
      personal care product (triclosan) and selected pharmaceuticals (venlafaxine,
      naproxen, and carbamazepine). The WASP 7.5 model was adapted and calibrated to
      reflect approximately ten kilometers of reach of the Grand River watershed that
      is highly influenced by a major urban WWTP. Simulation of the fate and transport
      of the target compounds revealed that flow-driven transport processes (advection
      and dispersion) greatly influenced the behavior of the target contaminants in the
      aquatic environment. However, fate mechanisms such as photolysis and
      biodegradation can play an important role in the attenuation of some compounds.
      The exception was carbamazepine where it was shown to act as a conservative
      tracer compound for wastewater specific contaminants in the water phase. The
      calibrated water quality model can now be employed in a number of future
      applications. Prediction of fate and transport of other trace organic
      contaminants across the watershed and assessment of the performance of WWTP
      infrastructure upgrades in the removal of these compounds are just a few
      examples. 

PMID- 24727038
TI  - Sedimentary records of delta(13)C, delta(15)N and organic matter accumulation in
      lakes receiving nutrient-rich mine waters.
AB  - Organic C and total N concentrations, C/N ratios, delta(15)N and delta(13)C
      values in (210)Pb-dated sediment cores were used to reconstruct historical
      changes in organic matter (OM) accumulation in three Swedish lakes receiving
      nutrient-rich mine waters. Ammonium-nitrate-based explosives and sodium cyanide
      (NaCN) used in gold extraction were the major N sources, while lesser amounts of
      P originated from apatite and flotation chemicals. The software IsoSource was
      used to model the relative contribution of soil, terrestrial and littoral
      vegetation, and phytoplankton detritus in the lake sediments. In one lake the
      IsoSource modelling failed, suggesting the presence of additional, unknown OM
      sources. In two of the lakes sedimentary detritus of littoral vegetation and
      phytoplankton had increased by 15-20% and 20-35%, respectively, since ~1950, when
      N- and P-rich mine waters began to reach the lakes. Today, phytoplankton is the
      dominating OM component in these lake sediments, which appears to be a
      eutrophication effect related to mining operations. Changes in the N isotopic
      composition of biota, lake water, and sediments related to the use of ammonium
      nitrate-based explosives and NaCN were evident in the two studied systems.
      However, N isotope signals in the receiving waters (delta(15)N~+90/00 to +190/00)
      were clearly shifted from the primary signal in explosives (delta(15)N-NO3=+3.4+/
      0.30/00; delta(15)N-NH4=-8.0+/-0.30/00) and NaCN (delta(15)N=+1.1+/-0.50/00), and
      direct tracing of the primary N isotope signals in mining chemicals was not
      possible in the receiving waters. Systems where mine waters with a well known
      discharge history are a major point source of N with well-defined isotopic
      composition should, however, be suitable for further studies of processes
      controlling N isotope signatures and their transformation in aquatic systems
      receiving mine waters.

PMID- 24727039
TI  - Estrogenic activity and cytotoxicity of six anticancer drugs detected in water
      systems.
AB  - The aim of the present study was to investigate the in vitro estrogenic and the
      cytotoxic activity of six cytostatics (5-fluorouracil, capecitabine, cisplatin,
      doxorubicin, etoposide, and imatinib) belonging to the five classes of Anatomical
      Therapeutic Classification (ATC) detected in wastewater systems. The estrogenic
      activity was assessed by YES-assay on Saccharomyces cerevisiae-RMY326 and E
      screen on MCF-7 cells. The cytotoxic activity was assessed by MTT Cell
      Proliferation Assay on the MCF-7 and the MDA-MB-231 cells. The results of
      estrogenic activity, detected by E-screen and expressed as EC50, showed a high
      potential of imatinib (10(-7) MUM) followed by cisplatin and 5-fluorouracil.
      Capecitabine was poorly estrogenic while etoposide and doxorubicin EC50 values
      were not possible to determine. Cytotoxicity was found at concentrations far from
      those detected in effluents. The potential endocrine activity of the most active
      drugs could be associated with human and wildlife risk when considering their
      occurrence in the environment.

PMID- 24727040
TI  - Cadmium and other heavy metal concentrations in bovine kidneys in the Republic of
      Ireland.
AB  - In Ireland, an estimated 15% of Irish soils exceed the EU threshold limit for
      soil Cd of 1mg/kg. The aim was to determine the concentrations of Cd and other
      heavy metals (As, Hg and Pb) in kidneys collected from cattle at slaughter.
      Systematic sampling of eligible animals (animals that were born and reared until
      slaughter in the same Irish county) at the time of slaughter was conducted, until
      a threshold number of animals from all 26 counties and 6 age categories was
      reached. A predictive surface of soil Cd was generated, by kriging the Cd values
      of 1310 previously reported soil samples. A linear regression weighted model was
      developed to model kidney Cd concentration, using the risk factors of age, sex,
      breed, province and estimated soil Cd concentration. Kidney Cd (n=393)
      concentrations varied between 0.040 and 8.630 mg/kg wet weight; while
      concentrations of As, Hg and Pb were low. The estimated weighted proportion of
      animals with a high (>=1 mg/kg) kidney Cd concentration was 11.25% (95% CI: 8.63
      14.53%). Key predictors for high kidney Cd concentration were soil Cd, animal age
      and province. At a soil Cd concentration of 1.5 mg/kg, it was predicted that an
      age threshold to avoid exceeding a kidney Cd concentration of 1 mg/kg in most
      animals would be ~3 y in Connacht, >4 y in Ulster, and >5 y in Leinster and
      Munster. In naturally occurring areas of high Cd levels in soils in Ireland, the
      Cd level in bovine kidneys can exceed the current EU ML of 1mg/kg in older
      animals. Kidneys of most cattle under three years of age will conform with EU
      requirements.

PMID- 24727041
TI  - Exchangeable and secondary mineral reactive pools of aluminium in coastal lowland
      acid sulfate soils.
AB  - The use of coastal floodplain sulfidic sediments for agricultural activities has
      resulted in the environmental degradation of many areas worldwide. The generation
      of acidity and transport of aluminium (Al) and other metals to adjacent aquatic
      systems are the main causes of adverse effects. Here, a five-step sequential
      extraction procedure (SEP) was applied to 30 coastal lowland acid sulfate soils
      (CLASS) from north-eastern New South Wales, Australia. This enabled
      quantification of the proportion of aluminium present in 'water-soluble',
      'exchangeable', 'organically-complexed', 'reducible iron(III)
      (oxyhydr)oxide/hydroxysulfate-incorporated' and 'amorphous Al mineral' fractions.
      The first three extractions represented an average of 5% of 'aqua regia'
      extractable Al and their cumulative concentrations were extremely high, reaching
      up to 4000 mg.kg(-1). Comparison of Al concentrations in the final two
      extractions indicated that 'amorphous Al minerals' are quantitatively a much more
      important sink for the removal of aqueous Al derived from the acidic weathering
      of these soils than reducible Fe(III) minerals. Correlations were observed
      between soil pH, dissolved and total organic carbon (DOC and TOC) and Al
      concentrations in organic carbon-rich CLASS soil horizons. These results suggest
      that complexation of Al by dissolved organic matter significantly increases
      soluble Al concentrations at pH values >5.0. As such, present land management
      practices would benefit with redefinition of an 'optimal' soil from pH >=5.5 to
      ~4.8 for the preservation of aquatic environments adjacent to organic-rich CLASS
      where Al is the sole or principle inorganic contaminant of concern. Furthermore,
      it was observed that currently-accepted standard procedures (i.e. 1 M KCl
      extraction) to measure exchangeable Al concentrations in these types of soils
      severely underestimate exchangeable Al and a more accurate representation may be
      obtained through the use of 0.2 M CuCl2.

PMID- 24727042
TI  - Compiling and using input-output frameworks through collaborative virtual
      laboratories.
AB  - Compiling, deploying and utilising large-scale databases that integrate
      environmental and economic data have traditionally been labour- and cost
      intensive processes, hindered by the large amount of disparate and misaligned
      data that must be collected and harmonised. The Australian Industrial Ecology
      Virtual Laboratory (IELab) is a novel, collaborative approach to compiling large
      scale environmentally extended multi-region input-output (MRIO) models. The
      utility of the IELab product is greatly enhanced by avoiding the need to lock in
      an MRIO structure at the time the MRIO system is developed. The IELab advances
      the idea of the "mother-daughter" construction principle, whereby a regionally
      and sectorally very detailed "mother" table is set up, from which "daughter"
      tables are derived to suit specific research questions. By introducing a third
      tier - the "root classification" - IELab users are able to define their own
      mother-MRIO configuration, at no additional cost in terms of data handling.
      Customised mother-MRIOs can then be built, which maximise disaggregation in
      aspects that are useful to a family of research questions. The second innovation
      in the IELab system is to provide a highly automated collaborative research
      platform in a cloud-computing environment, greatly expediting workflows and
      making these computational benefits accessible to all users. Combining these two
      aspects realises many benefits. The collaborative nature of the IELab development
      project allows significant savings in resources. Timely deployment is possible by
      coupling automation procedures with the comprehensive input from multiple teams.
      User-defined MRIO tables, coupled with high performance computing, mean that MRIO
      analysis will be useful and accessible for a great many more research
      applications than would otherwise be possible. By ensuring that a common set of
      analytical tools such as for hybrid life-cycle assessment is adopted, the IELab
      will facilitate the harmonisation of fragmented, dispersed and misaligned raw
      data for the benefit of all interested parties. 

PMID- 24727043
TI  - Tracing sources of organic matter in adjacent urban streams having different
      degrees of channel modification.
AB  - Urbanization and stream-channel modifications affect organic matter
      concentrations and quality in streams, by altering allochthonous organic matter
      input and in-stream transformation. This study uses multiple tracers (delta(13)C,
      delta(15)N, C/N ratio, and chlorophyll-a) to track sources of organic matter in
      two highly urbanized bayous in Houston (Texas, USA). Wastewater treatment plants
      (WWTPs) are located in headwaters of both bayous and contribute more than 75% to
      water flow. Low isotopic relatedness to natural end-members and enriched
      delta(15)N values suggest the influence of WWTPs on the composition of all
      organic matter fractions. The two bayous differ in degree of channel improvement
      resulting in different responses to hydrological conditions. During high flow
      conditions, the influence of terrestrial organic matter and sediment resuspension
      was much more pronounced in the Buffalo Bayou than in the concrete-lined White
      Oak Bayou. Particulate organic matter (POM) in White Oak Bayou had similar values
      of enriched delta(15)N in all subsegments, whereas in Buffalo Bayou, the degree
      of delta(15)N enrichment was less in the subsegments of the lower watershed. The
      difference in riparian zone contributions and interactions with sediments/soils
      was likely responsible for the compositional differences between the two bayous.
      Phytoplankton inputs were significantly higher in the bayous, especially in slow
      flowing sections, relative to the reference sites, and elevated phytoplankton
      inputs accounted for the observed stable C isotope differences between FPOM and
      high molecular weight dissolved organic matter (HMW DOM). Relative to POM, HMW
      DOM in the bayous was similar to WWTP effluents and showed minor longitudinal
      variability in both streams suggesting that WWTPs contribute much of the DOM in
      the systems. Urbanization has a major influence on organic matter sources and
      quality in these urban water bodies and these changes seem further enhanced by
      stream channel modifications. 

PMID- 24727044
TI  - Photocatalytic degradation of carbamazepine in wastewater by using a new class of
      whey-stabilized nanocrystalline TiO2 and ZnO.
AB  - Nanoscale photocatalysts have attracted much attention due to their high surface
      area to volume ratios. However, due to extremely high reactivity, TiO2 and ZnO
      nanoparticles prepared using different methods tend to either react with
      surrounding media or agglomerate, resulting in the formation of much larger flocs
      and significant loss in reactivity. This work investigates the photocatalytic
      degradation of carbamazepine (CBZ), a persistent pharmaceutical compound from
      wastewater (WW) using TiO2 and ZnO nanoparticles prepared in the presence of a
      water-soluble whey powder as stabilizer. The TiO2 and ZnO nanoparticles prepared
      in the presence of whey stabilizer displayed much less agglomeration and greater
      degradation power than those prepared without a stabilizer. Higher photocatalytic
      degradation of carbamazepine was observed (100%) by using whey stabilized TiO2
      nanoparticles with 55 min irradiation time as compared to ZnO nanoparticles
      (92%). The higher degradation of CBZ in wastewater by using TiO2 nanoparticles as
      compared to ZnO nanoparticles was due to formation of higher photo-generated
      holes with high oxidizing power of TiO2. The photocatalytic capacity of ZnO
      anticipated as similar to that of TiO2 as it has the same band gap energy (3.2
      eV) as TiO2. However, in the case of ZnO, photocorrosion frequently occurs with
      the illumination of UV light and this phenomenon is considered as one of the main
      reasons for the decrease of ZnO photocatalytic activity in aqueous solutions.
      Further, the estrogenic activity of photocatalyzed WW sample with CBZ and its by
      products was carried out by yeast estrogen screen (YES) assay method. Based upon
      the YES test results, none of the samples showed estrogenic activity.

PMID- 24727045
TI  - Natural and anthropogenic sources and processes affecting water chemistry in two
      South Korean streams.
AB  - Acid mine drainage (AMD) in a watershed provides potential sources of pollutants
      for surface and subsurface waters that can deteriorate water quality. Between
      March and early August 2011, water samples were collected from two streams in
      South Korea, one dominantly draining a watershed with carbonate bedrock affected
      by coal mines and another draining a watershed with silicate bedrock and a
      relatively undisturbed catchment area. The objective of the study was to identify
      the sources and processes controlling water chemistry, which was dependent on
      bedrock and land use. In the Odae stream (OS), the stream in the silicate
      dominated catchment, Ca, Na, and HCO3 were the dominant ions and total dissolved
      solids (TDS) was low (26.1-165 mg/L). In the Jijang stream (JS), in the carbonate
      dominated watershed, TDS (224-434 mg/L) and ion concentrations were typically
      higher, and Ca and SO4 were the dominant ions due to carbonate weathering and
      oxidation of pyrite exposed at coal mines. Dual isotopic compositions of sulfate
      (delta(34)SSO4 and delta(18)OSO4) verified that the SO4 in JS is derived mainly
      from sulfide mineral oxidation in coal mines. Cl in JS was highest upstream and
      decreased progressively downstream, which implies that pollutants from
      recreational facilities in the uppermost part of the catchment are the major
      source governing Cl concentrations within the discharge basin. Dual isotopic
      compositions of nitrate (delta(15)NNO3 and delta(18)ONO3) indicated that NO3 in
      JS is attributable to nitrification of soil organic matter but that NO3 in OS is
      derived mostly from manure. Additionally, the contributions of potential
      anthropogenic sources to the two streams were estimated in more detail by using a
      plot of delta(34)SSO4 and delta(15)NNO3. This study suggests that the dual
      isotope approach for sulfate and nitrate is an excellent additional tool for
      elucidating the sources and processes controlling the water chemistry of streams
      draining watersheds having different lithologies and land-use patterns.

PMID- 24727046
TI  - Changes in acidity and metal geochemistry in soils, groundwater, drain and river
      water in the Lower Murray River after a severe drought.
AB  - Acid sulfate soils with sulfuric material (pH<4) can have significant impacts on
      surface water quality and aquatic ecosystems due to low pH and high soluble metal
      concentrations in runoff and drainage discharges. There has been limited research
      on the complex geochemical transformations that occur along flow pathways from
      the soil acidity source to receiving waters. We studied the integrated
      geochemistry of metals in acid sulfate soils with sulfuric material, groundwater,
      drain and river water in the Lower Murray River (South Australia) over a 2 year
      period. The oxidation of an estimated 3500 ha of acid sulfate soils with sulfidic
      material (pH>4) underlying this former floodplain occurred due to falling river
      and groundwater levels during the 2006-2010 extreme "millennium" drought. A low
      pH (<4.5) soil layer was found approximately 1-2.5m below ground level with
      substantial amounts (up to 0.2 mol H(+)/kg dry weight) of available/soluble
      acidity and retained acidity in the form of the Fe oxyhydroxy sulfate mineral
      jarosite. The jarosite appears to be dissolving over time and buffering the sub
      surface soil layers at pH~4. Metal (Fe, Al, Mn) and metalloid (As) lability was
      greatly increased in the acidic soil layer. Highly acidic and metal rich
      groundwater (median pH 4.3, Fe, Al, Mn of 0.04-0.52 mmol/L) was observed at the
      same depths as the acidic soil layers. Nearly all of the dissolved Fe in the
      groundwater was present as Fe(2+). In the drains, increases in pH and redox
      potential promoted formation of the Fe oxyhydroxysulfate mineral schwertmannite.
      This mineral precipitation transferred a portion of the dissolved acidity to the
      drain sediments. Upon discharge to, and dilution of, the acid drainage in the
      river, pH neutralisation and rapid oxidation, hydrolysis, and precipitation of
      solid Al and Fe phases occurred in a localised area. Acidity is persisting (>3
      years) following a return to pre-drought water levels.

PMID- 24727047
TI  - Finite mixture models to characterize and refine air quality monitoring networks.
AB  - BACKGROUND: Existing air quality monitoring programs are, on occasion, not
      updated according to local, varying conditions and as such the monitoring
      programs become non-informative over time, under-detecting new sources of
      pollutants or duplicating information. Furthermore, inadequate maintenance may
      cause the monitoring equipment to be utterly deficient in providing information.
      To deal with these issues, a combination of formal statistical methods is used to
      optimize resources for monitoring and to characterize the monitoring networks,
      introducing new criteria for their refinement. METHODS: Monitoring data were
      obtained on key pollutants such as carbon monoxide (CO), nitrogen dioxide (NO2),
      ozone (O3), particulate matter (PM10) and sulfur dioxide (SO2) from 12 air
      quality monitoring sites in Seville (Spain) during 2012. A total of 49 data sets
      were fit to mixture models of Gaussian distribution using the expectation
      maximization (EM) algorithm. To summarize these 49 models, the mean and
      coefficient of variation were calculated for each mixture and carried out a
      hierarchical clustering analysis (HCA) to study the grouping of the sites
      according to these statistics. To handle the lack of observational data from the
      sites with unmonitored pollutants, the missing statistical values were imputed by
      applying the random forests technique and then later, a principal component
      analysis (PCA) was carried out to better understand the relationship between the
      level of pollution and the classification of monitoring sites. All of the
      techniques were applied using free, open-source, statistical software. RESULTS
      AND CONCLUSION: One example of source attribution and contribution is analyzed
      using mixture models and the potential for mixture models is posed in
      characterizing pollution trends. The mixture statistics have proven to be a
      fingerprint for every model and this work presents a novel use of them and
      represents a promising approach to characterizing mixture models in the air
      quality management discipline. The imputation technique used is allowed for
      estimating the missing information from key unmonitored pollutants to gather
      information about unknown pollution levels and to suggest new possible monitoring
      configurations for this network. Posterior PCA confirmed the misclassification of
      one site detected with HCA. The authors consider the stepwise approach used in
      this work to be promising and able to be applied to other air monitoring network
      studies.

PMID- 24727048
TI  - Behaviour of nonsteroidal anti-inflammatory drugs and eight of their metabolites
      during wastewater treatment studied by hollow fibre liquid phase microextraction
      and liquid chromatography mass spectrometry.
AB  - In this work hollow fibre liquid phase microextraction combined with liquid
      chromatography mass spectrometry was applied for the determination of the
      nonsteroidal anti-inflammatory drugs (NSAIDs) ketoprofen, naproxen, diclofenac
      and ibuprofen as well as eight of their known human metabolites in wastewater
      samples. Extraction time and addition of tri-n-octylphosphine oxide (TOPO) to the
      liquid membrane were evaluated resulting in a method with an optimal extraction
      time of 5h and 5% (w/V) TOPO addition to the membrane liquid (di-n-hexyl ether).
      With the optimized method, enrichment factors ranged between 778 and 4830. The
      method was applied for analysis of samples collected from Kallby wastewater
      treatment plant in the city of Lund, Sweden. Samples were collected from the
      influent, water entering as well as exiting the conventional activated sludge
      treatment and the effluent to study the behaviour of these compounds during the
      treatment process. All twelve substances were found in the influent and for all
      four drugs, higher concentrations were detected of the metabolites than the
      parent compounds. Highest concentrations were detected of o-desmethylnaproxen, 2
      hydroxyibuprofen and carboxyibuprofen (average influent concentrations of 45, 35
      and 63 MUg/L respectively). The study showed only partial removal during the
      primary treatment whereas both parent compounds and metabolites were efficiently
      removed during the activated sludge process. In the effluent all analytes were
      detected in concentrations below 1 MUg/L thus showing that either the
      investigated metabolites do not belong to the NSAID transformation products
      formed during the activated sludge treatment or they are also quickly further
      transformed within the treatment.

PMID- 24727050
TI  - Flaxseed oil during lactation changes milk and body composition in male and
      female suckling pups rats.
AB  - We have reported several changes in neonate or adult offspring after the maternal
      use of whole flaxseed or its components. However, it is unknown the use of higher
      oil intake in the neonatal period. Here we evaluated the effects of high maternal
      intake of flaxseed oil during lactation upon milk and body composition in male
      and female offspring. Lactating rats were divided into: (1) control (C, n=10), 7%
      soybean oil; (2) hyper 19% soybean oil (HS, n=10); and (3) hyper 17% flaxseed
      oil+2% soybean oil (HF, n=10). Dams and offspring were killed at weaning. HS and
      HF dams, male and female offspring presented lower body weight during lactation.
      HF mothers presented lower body and visceral fat masses. HF male offspring
      presented lower body and subcutaneous fat masses. HS and HF milk presented lower
      triglycerides (TG) and cholesterol. HF male and female offspring showed lower
      triglyceridemia and insulinemia, but no changes in glycemia and leptinemia. The
      higher intake of flaxseed oil during lactation reduced the body weight of mothers
      and offspring, decreases milk lipids and apparently increases insulin sensitivity
      in this critical period of life. Those changes may explain the previously
      reported programming effect of maternal flaxseed intake during lactation. 

PMID- 24727049
TI  - Evaluation of human health risks posed by carcinogenic and non-carcinogenic
      multiple contaminants associated with consumption of fish from Taihu Lake, China.
AB  - The present study estimated the human daily intake and uptake of organochlorine
      pesticides (OCPs), polychlorinated biphenyls (PCBs), polybrominated diphenyl
      ethers (PBDEs), polycyclic aromatic hydrocarbons (PAHs), and toxic trace elements
      [mercury (Hg), chromium (Cr), cadmium (Cd), and arsenic (As)] due to consumption
      of fish from Taihu Lake, China, and the associated potential health risks posed
      by these contaminants. The health risks posed by the contaminants were assessed
      using a risk quotient of the fish consumption rate to the maximum allowable fish
      consumption rate considering the contaminants for carcinogenic and non
      carcinogenic effect endpoints. The results showed that fish consumption would not
      pose non-cancer risks. However, some species would cause a cancer risk. Relative
      risks of the contaminants were calculated to investigate the contaminant which
      posed the highest risk to humans. As a result, in view of the contaminants for
      carcinogenic effects, As was the contaminant which posed the highest risk to
      humans. However, when non-carcinogenic effects of the contaminants were
      considered, Hg posed the highest risk. The risk caused by PBDEs was negligible.
      The results demonstrated that traditional contaminants, such as As, Hg, DDTs
      (dichlorodiphenyltrichloroethane and its metabolites), and PCBs, require more
      attention in Taihu Lake than the other target contaminants. 

PMID- 24727051
TI  - Effects of melatonin on aluminium-induced neurobehavioral and neurochemical
      changes in aging rats.
AB  - This study aimed to investigate the potential protective effects of melatonin
      (Mel) against aluminium-induced neurodegenerative changes in aging Wistar rats
      (24-28months old). Herein, aluminium chloride (AlCl3) (50mg/kg BW/day) was
      administered by gavage, and melatonin (Mel) was co-administered to a group of Al
      treated rats by an intra-peritoneal injection at a daily dose of 10mg/kg BW for
      four months. The findings revealed that aluminium administration induced a
      significant decrease in body weight associated with marked mortality for the old
      group of rats, which was more pronounced in old Al-treated rats. Behavioural
      alterations were assessed by 'open fields', 'elevated plus maze' and 'Radial 8
      arms maze' tests. The results demonstrated that Mel co-administration alleviated
      neurobehavioral changes in both old and old Al-treated rats. Melatonin was noted
      to play a good neuroprotective role, reducing lipid peroxidation (TBARs), and
      enhancing enzymatic (SOD, CAT and GPx) activities in the brain organs of old
      control and old Al-treated rats. Mel treatment also reversed the decrease of AChE
      activity in the brain tissues, which was confirmed by histological sections.
      Overall, the results showed that Mel administration can induce beneficial effects
      for the treatment of Al-induced neurobehavioral and neurochemical changes in the
      central nervous system (CNS). 

PMID- 24727052
TI  - Evaluation of circulating cathodic antigen (CCA) urine-cassette assay as a survey
      tool for Schistosoma mansoni in different transmission settings within Bugiri
      District, Uganda.
AB  - Diagnosis of schistosomiasis at the point-of-care (POC) is a growing topic in
      neglected tropical disease research. There is a need for diagnostic tests which
      are affordable, sensitive, specific, user-friendly, rapid, equipment-free and
      delivered to those who need it, and POC is an important tool for disease mapping
      and guiding mass deworming. The aim of present study was to evaluate the relative
      diagnostic performance of two urine-circulating cathodic antigen (CCA) cassette
      assays, one commercially available and the other in experimental production,
      against results obtained using the standard Kato-Katz faecal smear method (six
      thick smears from three consecutive days), as a 'gold-standard', for Schistosoma
      mansoni infection in different transmission settings in Uganda. Our study was
      conducted among 500 school children randomly selected across 5 schools within
      Bugiri district, adjacent to Lake Victoria in Uganda. Considering results from
      the 469 pupils who provided three stool samples for the six Kato-Katz smears, 293
      (76%) children had no infection, 109 (23%) were in the light intensity category,
      while 42 (9%) and 25 (5%) were in the moderate and heavy intensity categories
      respectively. Following performance analysis of CCA tests in terms of
      sensitivity, specificity, negative and positive predictive values, overall
      performance of the commercially available CCA test was more informative than
      single Kato-Katz faecal smear microscopy, the current operational field standard
      for disease mapping. The current CCA assay is therefore a satisfactory method for
      surveillance of S. mansoni in an area where disease endemicity is declining due
      to control interventions. With the recent resolution on schistosomiasis
      elimination by the 65th World Health Assembly, the urine POC CCA test is an
      attractive tool to augment and perhaps replace the Kato-Katz sampling within
      ongoing control programmes. 

PMID- 24727053
TI  - High prevalence of PfCRT K76T mutation in Plasmodium falciparum isolates in
      Ghana.
AB  - Plasmodium falciparum has successfully developed resistance to almost all
      currently used antimalarials. A single nucleotide polymorphism in the P.
      falciparum chloroquine resistance transporter (Pfcrt) gene at position 76
      resulting in a change in coding from lysine to threonine (K76T) has been
      implicated to be the corner stone of chloroquine resistance. Widespread
      resistance to chloroquine in endemic regions led to its replacement with other
      antimalarials. In some areas this replacement resulted in a reversion of the
      mutant T76 allele to the wild-type K76 allele. This study was conducted to
      determine the prevalence of the K76T mutation of the Pfcrt gene eight years after
      the ban on chloroquine sales and use. A cross-sectional study was conducted in 6
      regional hospitals in Ghana. PCR-RFLP was used to analyse samples collected to
      determine the prevalence of Pfcrt K76T mutation. Of the 1318 participants
      recruited for this study, 246 were found to harbour the P. falciparum parasites,
      of which 60.98% (150/246) showed symptoms for malaria. The prevalence of the
      Pfcrt T76 mutant allele was 58.54% (144/246) and that of the K76 wild-type allele
      was 41.46% (102/246). No difference of statistical significance was observed in
      the distribution of the alleles in the symptomatic and asymptomatic participants
      (P=0.632). No significant association was, again, observed between the alleles
      and parasite density (P=0.314), as well as between the alleles and Hb levels of
      the participants (P=0.254). Notwithstanding the decline in the prevalence of the
      Pfcrt T76 mutation since the antimalarial policy change in 2004, the 58.54%
      prevalence recorded in this study is considered high after eight years of the
      abolishment of chloroquine usage in Ghana. This is in contrast to findings from
      other endemic areas where the mutant allele significantly reduced in the
      population after a reduction chloroquine use. 

PMID- 24727054
TI  - Mosaicism for c.431_454dup in ARX causes a mild Partington syndrome phenotype.
AB  - A common in frame duplication in ARX (c.431_454dup24) was found in a five year
      old boy who presented with mild Partington syndrome. The duplication was detected
      by PCR amplification followed by fragment length analysis and was located in exon
      2 spanning the two polyalanine tracts commonly seen to expand. Detection of the
      duplication by DNA sequencing was difficult due to preferential sequencing of the
      normal allele, demonstrating the superiority of fragment length analysis in
      mosaic cases. The clinical symptoms were mild to moderate developmental delay
      with only the hand dystonia to suggest Partington syndrome. This patient is the
      first male reported to be mosaic for the duplication, and his clinical features
      are subtle. This study shows that in males with a phenotype of mild Partington
      syndrome and in heterozygous females fragment length analysis should be preferred
      over DNA sequencing.

PMID- 24727055
TI  - LEC1-LIKE paralog transcription factor: how to survive extinction and fit in NF-Y
      protein complex.
AB  - Transcription factor function is crucial for eukaryotic systems. The presence of
      transcription factor families in genomes represents a significant technical
      challenge for functional studies. To understand their function, we must
      understand how they evolved and maintained by organisms. Based on genome scale
      searches for homologs of LEAFY COTYLEDON-LIKE (L1L; AtNF-YB6), NF-YB
      transcription factor, we report the discovery and annotation of a complete
      repertoire of thirteen novel genes that belong to the L1L paralogous gene family
      of Solanum lycopersicum. Gene duplication events within the species resulted in
      the expansion of the L1L family. Sequence and structure-based phylogenetic
      analyses revealed two distinct groups of L1Ls in tomato. Natural selection
      appears to have contributed to the asymmetric evolution of paralogs. Our results
      point to key differences among SlL1L paralogs in the presence of motifs,
      structural features, cysteine composition and expression patterns during plant
      and fruit development. Furthermore, differences in the binding domains of L1L
      members suggest that some of them evolved new binding specificities. These
      results reveal dramatic functional diversification of L1L paralogs for their
      maintenance in tomato genome. Our comprehensive insights on tomato L1L family
      should provide the basis for further functional and genetic experimentation.

PMID- 24727056
TI  - PLIN1 deficiency affects testicular gene expression at the meiotic stage in the
      first wave of spermatogenesis.
AB  - PLIN1, a lipid droplet associated protein, has been implicated in playing a key
      role in the regulation of lipolysis and lipid storage in adipocytes. PLIN1 is
      found to be highly expressed in Leydig cells of testis, suggesting a potential
      role in steroidogenesis and spermatogenesis. In this study, we showed that PLIN1
      was expressed in testis and that its mRNA levels declined significantly with
      development. To investigate the role of PLIN1, we take advantage of PLIN1-null
      mice. We found that the number of seminiferous tubules containing round
      spermatids was significantly increased at P21 (postnatal day 21). Furthermore,
      microarray analysis showed that there were 538 differentially expressed genes
      between PLIN1-null and wild-type mice at P21. The up-regulated genes in knockout
      mice were enriched in spermatogenesis by Gene Ontology classification. Among
      them, Prm1 and Wbp2nl are important for spermatogenesis which were confirmed by
      real-time PCR. Unexpectedly, the levels of serum testosterone and serum 17beta
      estradiol as well as steroidogenic genes are not altered in the PLIN1-null mice.
      Compared to the wild-type mice, no significant difference of fertility was found
      in the PLIN1-null mice. Therefore, these findings indicated that PLIN1 disruption
      leads to the increase of round spermatid-containing seminiferous tubules at the
      meiotic stage of the first wave of spermatogenesis through regulating
      spermatogenic related genes.

PMID- 24727058
TI  - Penetration of normal, damaged and diseased skin--an in vitro study on dendritic
      core-multishell nanotransporters.
AB  - A growing intended or accidental exposure to nanoparticles asks for the
      elucidation of potential toxicity linked to the penetration of normal and
      lesional skin. We studied the skin penetration of dye-tagged dendritic core
      multishell (CMS) nanotransporters and of Nile red loaded CMS nanotransporters
      using fluorescence microscopy. Normal and stripped human skin ex vivo as well as
      normal reconstructed human skin and in vitro skin disease models served as test
      platforms. Nile red was delivered rapidly into the viable epidermis and dermis of
      normal skin, whereas the highly flexible CMS nanotransporters remained solely in
      the stratum corneum after 6h but penetrated into deeper skin layers after 24h
      exposure. Fluorescence lifetime imaging microscopy proved a stable dye-tag and
      revealed striking nanotransporter-skin interactions. The viable layers of
      stripped skin were penetrated more efficiently by dye-tagged CMS nanotransporters
      and the cargo compared to normal skin. Normal reconstructed human skin reflected
      the penetration of Nile red and CMS nanotransporters in human skin and both, the
      non-hyperkeratotic non-melanoma skin cancer and hyperkeratotic peeling skin
      disease models come along with altered absorption in the skin diseases. 

PMID- 24727057
TI  - Genes involved in the regulation of vascular homeostasis determine renal survival
      rate in patients with chronic glomerulonephritis.
AB  - Chronic glomerulonephritis (CGN) is one of the most severe kidney diseases. Genes
      of vascular reactivity are thought to play an important role in development and
      progression of CGN. In this study, we analyzed association of genes of vascular
      homeostasis with hypertension and renal survival of CGN patients. The study
      sample included 238 patients with CGN and 304 healthy subjects of population
      control. Ten polymorphisms of ten genes of vascular homeostasis were genotyped
      through polymerase chain reaction (PCR), restriction fragment length polymorphism
      (RFLP) analysis and TaqMan assays. Association of the genotypes with renal
      survival was analyzed by the Kaplan-Meier estimator. Genotypes 311SC and 311SS of
      the PON2 gene, (-1166)AC and (-1166)CC of the AGTR1 gene, (+46)AA of the ADRB2
      gene, and 198KK and 198KN of the EDN1 gene were associated with decreased rate of
      renal survival of the patients. Polymorphisms S311C PON2, (-1166)A/C AGTR1,
      (+46)G/A ADRB2, and K198N EDN1 were associated with the accelerated decline in
      kidney function in the CGN patients.

PMID- 24727059
TI  - Poly(lactide-co-glycolide) microspheres for MRI-monitored transcatheter delivery
      of sorafenib to liver tumors.
AB  - The multi-kinase inhibitor (MKI) sorafenib can be an effective palliative therapy
      for patients with hepatocellular carcinoma (HCC). However, patient tolerance is
      often poor due to common systemic side effects following oral administration.
      Local transcatheter delivery of sorafenib to liver tumors has the potential to
      reduce systemic toxicities while increasing the dose delivered to targeted
      tumors. We developed sorafenib-eluting PLG microspheres for delivery by intra
      hepatic transcatheter infusion in an orthotropic rodent HCC model. The particles
      also encapsulated iron-oxide nanoparticles permitting magnetic resonance imaging
      (MRI) of intra-hepatic biodistributions. The PLG microspheres (diameter~1MUm)
      were loaded with 18.6% (w/w) sorafenib and 0.54% (w/w) ferrofluid and 65.2% of
      the sorafenib was released within 72h of media exposure. In vitro studies
      demonstrated significant reductions in HCC cell proliferation with increasing
      doses of the sorafenib-eluting microspheres, where the estimated IC50 was a
      29MUg/mL dose of microspheres. During in vivo studies, MRI permitted intra
      procedural visualization of intra-hepatic microsphere delivery. At 72h after
      microsphere infusion, microvessel density was significantly reduced in tumors
      treated with the sorafenib-eluting microspheres compared to both sham control
      tumors (by 35%) and controls (by 30%). These PLG microspheres offer the potential
      to increase the efficacy of molecularly targeted MKI therapies while reducing
      systemic exposures via selective catheter-directed delivery to HCC. 

PMID- 24727060
TI  - A new adjuvant delivery system 'cyclic di-GMP/YSK05 liposome' for cancer
      immunotherapy.
AB  - Cyclic dinucleotides are of importance in the field of microbiology and
      immunology. They function as second messengers and are thought to participate in
      the signal transduction of cytosolic DNA immune responses. One such dinucleotide,
      cyclic di-GMP (c-di-GMP), stimulates the immune system. It is thought that c-di
      GMP is recognized by ATP dependent RNA helicase (DDX41) in the cytosol, forms a
      complex with the Stimulator of interferon genes protein (STING), triggers a
      signal via the tank binding kinase 1-interferon regulatory factor 3 (TBK1-IRF3)
      pathway and induces the production of type I interferons. Therefore c-di-GMP can
      be thought of as a new class of adjuvant. However, because c-di-GMP contains two
      phosphate groups, this prevents its use as an adjuvant because it cannot pass
      through the cell membrane, even though the target molecule of c-di-GMP is located
      in the cytoplasm. Our group has been developing a series of liposomal drug
      delivery systems and recently investigated YSK05 which is a synthetic, pH
      sensitive lipid that has a high fusogenicity. We utilized this lipid as a carrier
      to transport c-di-GMP into the cytosol to then use c-di-GMP as an adjuvant. Based
      on screening experiments, YSK05/POPE/cholesterol=40/25/35 was found to induce IFN
      beta in Raw264.7 cells. The induction of IFN-beta from c-di-GMP liposomes was
      inhibited by adding BX795, a TBK1 inhibitor, indicating that the production of
      IFN-beta caused the activation of the STING-TBK1 pathway. C-di-GMP liposomes also
      showed significantly higher levels of expression of CD80, CD86 and MHC class I.
      The c-di-GMP/YSK05 liposome facilitated antigen specific cytotoxic T cell
      activity and the inhibition of tumor growth in a mouse model. These findings
      indicate that c-di-GMP/YSK05 liposomes could be used, not only to transfer c-di
      GMP to the cytosol and induce an innate immune system but also as a platform for
      investigating the mechanism of immune sensing with cyclic dinucleotides in vitro
      and in vivo. 

PMID- 24727061
TI  - Pneumoperitoneum in the presence of acute and chronic kidney injury: an
      experimental model in rats.
AB  - PURPOSE: There is evidence that pneumoperitoneum induces transient changes in
      renal function in healthy individuals. Its effect on malfunctioning kidneys is
      not well known. We investigated effects caused by pneumoperitoneum in animals
      with impaired renal function. MATERIALS AND METHODS: Male Wistar rats underwent
      subtotal (5/6) nephrectomy in 2 sequential steps to induce renal failure. Two and
      10 weeks postoperatively rats were classified with acute and chronic kidney
      injury, respectively. At those time points all rats were exposed to 0, 5 and 8 mm
      Hg pneumoperitoneum for 60 minutes. Changes in creatinine, blood urea nitrogen
      and creatinine clearance were measured. Histopathological changes and apoptosis
      were also evaluated in the subgroups. RESULTS: A total of 18 rats with acute and
      18 with chronic kidney injury completed the study. Creatinine and blood urea
      nitrogen did not change after applying pneumoperitoneum in the different pressure
      subgroups but creatinine clearance significantly decreased in the 5 and 8 mm Hg
      subgroups in rats with acute and chronic kidney injury. Histopathological
      findings in the acute kidney injury subgroups that underwent 5 and 8 mm Hg
      pressure revealed ischemic changes while compensatory hypertrophy was noticed in
      the chronic injury pressurized subgroups. The apoptotic count was significantly
      higher in the chronic injury subgroups compared to their acute injury pressurized
      counterparts. CONCLUSIONS: Pneumoperitoneum seems feasible in rats with impaired
      baseline renal function. Particularly chronic cases should not be considered a
      contraindication to pneumoperitoneum while in acute cases pneumoperitoneum might
      be detrimental.

PMID- 24727062
TI  - How should continence and incontinence after radical prostatectomy be evaluated?
      A prospective study of patient ratings and changes with time.
AB  - PURPOSE: We examined prevalence rates, and changes in continence and incontinence
      before and after radical prostatectomy for prostate cancer by comparing different
      definitions. We also studied the descriptive validity of the grading system of
      Ellison et al for post-prostatectomy incontinence and baseline predictors of post
      prostatectomy incontinence at 12 months. MATERIALS AND METHODS: This national
      prospective study included 844 patients treated with radical prostatectomy
      between 2005 and 2009. Adverse effects, including urinary dysfunction and bother,
      were reported by 735 patients (88%) using the EPIC-50 and UCLA-PCI validated
      questionnaires at baseline and 12-month followup. Linear regression analysis was
      done to examine baseline predictors and the degree of post-prostatectomy
      incontinence at followup. RESULTS: At 12 months after radical prostatectomy 74%
      of patients reported post-prostatectomy incontinence, of whom 40% used pads
      daily, 34% reported occasional dribbling without pads and 26% had total urinary
      control. When defined as total incontinence/no urinary control, severe post
      prostatectomy incontinence was reported by 3% of the men but 25% had severe post
      prostatectomy incontinence according to the stratification of Ellison et al. Of
      patients with preoperative incontinence 14% improved postoperatively. Predictors
      of post-prostatectomy incontinence were age 65 years or greater, not working,
      sexual dysfunction and incontinence preoperatively. The latter 2 remained the
      strongest predictors on multivariate analysis. Prostate cancer related variables
      were not associated with post-prostatectomy incontinence. CONCLUSIONS: The
      prevalence of post-prostatectomy incontinence varied considerably according to
      the definition applied. In our opinion incontinence may be reported as any
      leakage and not only as pad use with grading done on a symptom scale.
      Preoperative sexual dysfunction and urinary incontinence were the strongest
      predictors of post-prostatectomy incontinence at 12-month followup.

PMID- 24727063
TI  - Highly sensitive determination of methotrexate at poly (l-lysine) modified
      electrode in the presence of sodium dodecyl benzene sulfonate.
AB  - A simple and sensitive electrochemical sensor based on poly (l-lysine) modified
      glassy carbon electrode (PLL/GCE) was developed to sensitively detect
      methotrexate (MTX) in the presence of sodium dodecyl benzene sulfonate (SDBS).
      Fourier transform infrared spectroscopy, electrochemical impedance spectroscopy
      and cyclic voltammetry were carried out to characterize PLL film which exhibits
      excellent electrocatalytic activity toward the oxidation of MTX in 0.1M phosphate
      buffer solution. In addition, the oxidation peak of MTX remained stable at
      PLL/GCE in the presence of SDBS and its current increased 8 times compared with
      that at bare GCE without SDBS. Experimental parameters were optimized with regard
      to pH, electro-polymerization segment, accumulation time and concentration of
      SDBS. Under optimum conditions, the square wave voltammograms exhibited that the
      oxidation peak current was linearly proportional to the concentration of MTX in
      the range of 5nM - 0.2MUM with detection limit of 1.7 (+/-0.06) nM (S/N=3).
      Moreover, this method was applied to detect MTX in medicinal tablets with
      satisfying results. 

PMID- 24727064
TI  - The C. elegans lifespan assay toolkit.
AB  - Since the discovery of single gene mutations that double its lifespan, the
      nematode Caenorhabditis elegans has provided remarkable insights into the biology
      of aging. The precisely measurable lifespan of worms has proven to be an
      efficient tool to assess the impact of various genetic, physiological and
      environmental factors on organismal aging. In this article, we describe methods
      to set up and monitor experiments to determine worm lifespan. We include
      procedures used for classical, small-scale lifespan assays that are generally
      performed on solid media, and review recent advances in high-throughput,
      automated longevity experiments conducted in liquid culture and microfluidic
      devices. In addition, tools that help analyze this data to obtain survival
      statistics are summarized, and C. elegans strains that offer particular
      advantages for lifespan studies are listed. 

PMID- 24727065
TI  - The C. elegans healthspan and stress-resistance assay toolkit.
AB  - A wealth of knowledge on the genetic mechanisms that govern aging has emerged
      from the study of mutants that exhibit enhanced longevity and exceptional
      resilience to adverse environmental conditions. In these studies, lifespan has
      been an excellent proxy for establishing the rate of aging, but it is not always
      correlated with qualitative measures of healthy aging or 'healthspan'. Although
      the attributes of healthspan have been challenging to define, they share some
      universal features that are increasingly being incorporated into aging studies.
      Here we describe methods used to determine Caenorhabditis elegans healthspan.
      These include assessments of tissue integrity and functionality and resistance to
      a variety of biotic and abiotic stressors. We have chosen to include simple,
      rapid assays in this collection that can be easily undertaken in any C. elegans
      laboratory, and can be relied on to provide a preliminary but thorough insight
      into the healthspan of a population. 

PMID- 24727066
TI  - Bioaccumulation and biomagnification of emerging and classical flame retardants
      in bird eggs of 14 species from Donana Natural Space and surrounding areas (South
      western Spain).
AB  - The occurrence of classical (polybrominated diphenyl ethers, PBDEs) and emerging
      FRs (dechloranes, hexabromobenzene (HBB), pentabromoethyl benzene (PBEB) and
      decabromodiphenyl ethane (DBDPE)) in unborn eggs of 14 different species from
      Donana Natural Space and surrounding areas was studied. PBDEs, Dec-602, Dec-603
      and DP were detected in all the species, whereas HBB, PBEB, DBDPE and Dec-604
      were not detected in any sample. SigmaPBDE and SigmaDechlorane levels ranged from
      1.40 to 90.7, and from 0.77 to 260 ng/g lw, respectively. BDE-209 was the most
      abundant BDE congener in almost all the species, whereas Dec-602 was the
      predominant among dechloranes. In general, levels of PBDEs and dechloranes were
      similar and even higher for dechloranes, probably indicating the increasing use
      of dechloranes as a result of legal restrictions on PBDEs. In both cases, the
      most contaminated specie was the white stork. Using stable isotope
      characterization, differences among species and possible biomagnification
      processes were also evaluated. PBDE levels increased as the trophic position
      increased, showing biomagnification capacity. The same behavior was observed for
      Dec-602 and Dec-603; however, DP levels were not linearly correlated with trophic
      level. These results show that more attention should be given to emerging FRs
      such as dechloranes since they show similar environmental behavior as PBDEs.

PMID- 24727067
TI  - Population variation in biomonitoring data for persistent organic pollutants
      (POPs): an examination of multiple population-based datasets for application to
      Australian pooled biomonitoring data.
AB  - BACKGROUND: Australian national biomonitoring for persistent organic pollutants
      (POPs) relies upon age-specific pooled serum samples to characterize central
      tendencies of concentrations but does not provide estimates of upper bound
      concentrations. This analysis compares population variation from biomonitoring
      datasets from the US, Canada, Germany, Spain, and Belgium to identify and test
      patterns potentially useful for estimating population upper bound reference
      values for the Australian population. METHODS: Arithmetic means and the ratio of
      the 95th percentile to the arithmetic mean (P95:mean) were assessed by survey for
      defined age subgroups for three polychlorinated biphenyls (PCBs 138, 153, and
      180), hexachlorobenzene (HCB), p,p-dichlorodiphenyldichloroethylene (DDE),
      2,2',4,4' tetrabrominated diphenylether (PBDE 47), perfluorooctanoic acid (PFOA)
      and perfluorooctane sulfonate (PFOS). RESULTS: Arithmetic mean concentrations of
      each analyte varied widely across surveys and age groups. However, P95:mean
      ratios differed to a limited extent, with no systematic variation across ages.
      The average P95:mean ratios were 2.2 for the three PCBs and HCB; 3.0 for DDE; 2.0
      and 2.3 for PFOA and PFOS, respectively. The P95:mean ratio for PBDE 47 was more
      variable among age groups, ranging from 2.7 to 4.8. The average P95:mean ratios
      accurately estimated age group-specific P95s in the Flemish Environmental Health
      Survey II and were used to estimate the P95s for the Australian population by age
      group from the pooled biomonitoring data. CONCLUSIONS: Similar population
      variation patterns for POPs were observed across multiple surveys, even when
      absolute concentrations differed widely. These patterns can be used to estimate
      population upper bounds when only pooled sampling data are available.

PMID- 24727068
TI  - Short term variability in urinary bisphenol A in Australian children.
AB  - Used frequently in food contact materials, bisphenol A (BPA) has been studied
      extensively in recent years, and ubiquitous exposure in the general population
      has been demonstrated worldwide. Characterizing within- and between-individual
      variability of BPA concentrations is important for characterizing exposure in
      biomonitoring studies, and this has been investigated previously in adults, but
      not in children. The aim of this study was to characterize the short-term
      variability of BPA in spot urine samples in young children. Children aged >=2-<4
      years (n=25) were recruited from an existing cohort in Queensland, Australia, and
      donated four spot urine samples each over a two day period. Samples were analysed
      for total BPA using isotope dilution online solid phase extraction-liquid
      chromatography-tandem mass spectrometry, and concentrations ranged from 0.53 to
      74.5 ng/ml, with geometric mean and standard deviation of 2.70 ng/ml and 2.94
      ng/ml, respectively. Sex and time of sample collection were not significant
      predictors of BPA concentration. The between-individual variability was
      approximately equal to the within-individual variability (ICC=0.51), and this ICC
      is somewhat higher than previously reported literature values. This may be the
      result of physiological or behavioural differences between children and adults or
      of the relatively short exposure window assessed. Using a bootstrapping
      methodology, a single sample resulted in correct tertile classification
      approximately 70% of the time. This study suggests that single spot samples
      obtained from young children provide a reliable characterization of absolute and
      relative exposure over the short time window studied, but this may not hold true
      over longer timeframes.

PMID- 24727069
TI  - The human health effects of Florida red tide (FRT) blooms: an expanded analysis.
AB  - Human respiratory and digestive illnesses can be caused by exposures to
      brevetoxins from blooms of the marine alga Karenia brevis, also known as Florida
      red tide (FRT). K. brevis requires macro-nutrients to grow; although the sources
      of these nutrients have not been resolved completely, they are thought to
      originate both naturally and anthropogenically. The latter sources comprise
      atmospheric depositions, industrial effluents, land runoffs, or submerged
      groundwater discharges. To date, there has been only limited research on the
      extent of human health risks and economic impacts due to FRT. We hypothesized
      that FRT blooms were associated with increases in the numbers of emergency room
      visits and hospital inpatient admissions for both respiratory and digestive
      illnesses. We sought to estimate these relationships and to calculate the costs
      of associated adverse health impacts. We developed environmental exposure
      response models to test the effects of FRT blooms on human health, using data
      from diverse sources. We estimated the FRT bloom-associated illness costs, using
      extant data and parameters from the literature. When controlling for resident
      population, a proxy for tourism, and seasonal and annual effects, we found that
      increases in respiratory and digestive illnesses can be explained by FRT blooms.
      Specifically, FRT blooms were associated with human health and economic effects
      in older cohorts (>=55 years of age) in six southwest Florida counties. Annual
      costs of illness ranged from $60,000 to $700,000 annually, but these costs could
      exceed $1.0 million per year for severe, long-lasting FRT blooms, such as the one
      that occurred during 2005. Assuming that the average annual illness costs of FRT
      blooms persist into the future, using a discount rate of 3%, the capitalized
      costs of future illnesses would range between $2 and 24 million.

PMID- 24727070
TI  - Application of biochar to soil reduces cancer risk via rice consumption: a case
      study in Miaoqian village, Longyan, China.
AB  - Consumption of rice contaminated with potentially toxic elements (PTEs) is a
      major pathway for human exposure to PTEs. This is particularly true in China's so
      called "Cancer Villages". In this study, sewage sludge biochar (SSBC) was applied
      to soil (at 5% and 10%) to suppress PTE phytoavailability and as a consequence to
      reduce PTE levels in rice grown in mining impacted paddy soils. Risk assessment
      indicated that SSBC addition (10%) markedly (P<=0.05) decreased the daily intake,
      associated with the consumption of rice, of PTEs (As, Cd, Co, Cu, Mn, Pb and Zn
      by: 68, 42, 55, 29, 43, 38 and 22%, respectively). In treatments containing SSBC
      (10%) the health quotient (HQ) indices for PTEs (except for As, Cu and Mn) were
      <1, indicating that SSBC suppressed the health risk associated with PTEs in rice.
      The addition of SSBC (10%) markedly (P<=0.01) reduced AsIII (72%),
      dimethylarsinic acid (DMA) (74%) and AsV (62%) concentrations in rice.
      Consequentially, following SSBC application (10%), the incremental lifetime
      cancer (ILTR) value for iAs (AsIII+AsV) associated with the consumption of rice
      was significantly (P<=0.01) reduced by 66%. These findings suggest that SSBC
      could be a useful soil amendment to mitigating PTE exposure, through rice
      consumption, in China's "Cancer Villages". 

PMID- 24727071
TI  - Pollution: a global threat.
AB  - Over the past several decades, several large-scale seemingly unrelated events
      have unfolded in all corners of the world. Within the oceans, coral reef systems
      have been facing unprecedented mass bleaching episodes, sea turtles worldwide are
      currently experiencing an epidemic in the form of fibropapilloma, and global
      phytoplankton populations have declined by 40%. Within the Earth's terrestrial
      systems, similar phenomena have appeared in the form of colony collapse disorder
      (CCD) currently devastating honey bee colonies, White Nose Syndrome decimating
      bat populations, and the chytrid fungus plaguing amphibian populations. On the
      surface these events appear to be unrelated yet at the root of each phenomenon
      there appears an underlying threat - pollution. This paper will investigate the
      commonality of these occurrences as well as investigate the current and potential
      solutions to the threat. 

PMID- 24727072
TI  - Hypertensive disorders of pregnancy and gestational diabetes mellitus among
      French Caribbean women chronically exposed to chlordecone.
AB  - Few studies have explored the consequences of environmental exposure to
      organochlorine pesticides for gestational hypertension (GH), preeclampsia (PE)
      and gestational diabetes mellitus (GDM). Chlordecone is a persistent
      organochlorine pesticide that was used intensively, and almost exclusively, in
      the French West Indies until 1993. We investigated the impact of prenatal
      exposure to chlordecone on the occurrence of GDM, GH and PE by studying 779
      pregnant women enrolled in a prospective mother-child cohort (Timoun Study) in
      Guadeloupe between 2004 and 2007. Chlordecone exposure was determined by assaying
      maternal plasma and information about pregnancy complications was obtained from
      midwives, pediatricians and hospital medical records after delivery. The risks of
      GH (n=65), PE (n=31) and GDM (n=71) were estimated by multiple logistic
      regression including potential confounders. Levels of chlordecone plasma
      concentration in the third (OR=0.2; 95% confidence interval (CI): 0.1, 0.5) and
      fourth quartiles (OR=0.3; 95% CI: 0.2, 0.7) were associated with a statistically
      significant decrease in the risk of GH. A log10 increase in chlordecone
      concentration was significantly associated with lower risk of GH (OR=0.4; 95% CI:
      0.2, 0.6). No significant associations were observed between the chlordecone
      exposure and the risk of PE or GDM. This study suggests an inverse association
      between chlordecone exposure during pregnancy and GH. Further studies are
      required to determine the underlying mechanism, or the potential unknown
      confounding factors, resulting in this association. 

PMID- 24727073
TI  - A look inside an alkaloid multisite plant: the Catharanthus logistics.
AB  - Environmental pressures forced plants to diversify specialized metabolisms to
      accumulate noxious molecules such as alkaloids constituting one of the largest
      classes of defense metabolites. Catharanthus roseus produces monoterpene indole
      alkaloids via a highly elaborated biosynthetic pathway whose characterization
      greatly progressed with the recent expansion of transcriptomic resources. The
      complex architecture of this pathway, sequentially distributed in at least four
      cell types and further compartmentalized into several organelles, involves
      partially identified inter-cellular and intra-cellular translocation events
      acting as potential key-regulators of metabolic fluxes. The description of this
      spatial organization and the inherent secretion and sequestration of metabolites
      not only provide new insight into alkaloid cell biology and its involvement in
      plant defense processes but also present new biotechnological challenges for
      synthetic biology. 

PMID- 24727074
TI  - The chemical logic of plant natural product biosynthesis.
AB  - Understanding the logic of plant natural product biosynthesis is important for
      three reasons: it guides the search for new natural products and pathways,
      illuminates the function of existing pathways in the context of host biology, and
      builds an enabling 'parts list' for plant and microbial metabolic engineering. In
      this review, we highlight the chemical themes that underlie a broad range of
      plant pathways, dividing pathways into two parts: scaffold-generating steps that
      draw on a limited set of chemistries, and tailoring reactions that produce a wide
      range of end products from a small number of common scaffolds. 

PMID- 24727075
TI  - B cell-intrinsic toll-like receptor 7 is responsible for the enhanced anti-PEG
      IgM production following injection of siRNA-containing PEGylated lipoplex in
      mice.
AB  - Recently, we reported that immunostimulatory siRNA-containing PEGylated lipoplex
      (PEGylated siRNA-lipoplex) activates the immune system, resulting in the enhanced
      production of anti-PEG IgM. However, the enhancing mechanism upon anti-PEG IgM
      production has not been fully elucidated. In this study, we employed toll-like
      receptor 7 knock out (TLR7 KO) mice, and showed how PEGylated siRNA-lipoplex
      activates the innate immune system through TLR7 and consequently enhances anti
      PEG IgM production. In addition, we showed that SCID mice reconstituted with TLR7
      deficient B cells failed to enhance anti-PEG IgM production following the
      injection of PEGylated siRNA-lipoplex, but that SCID mice reconstituted with wild
      type B cells did enhance anti-PEG IgM production. These results suggest that
      immune activation via B cell-intrinsic TLR7, but not other TLR7-expressing cells,
      contributes predominantly to an enhanced anti-PEG IgM production in response to
      the intravenous injection of PEGylated siRNA-lipoplexes. A strategy to evade B
      cell-intrinsic TLR7 activation by siRNA, such as chemical modification, may
      overcome immunological barriers to PEGylated liposome-based siRNA therapeutics. 

PMID- 24727076
TI  - Cationic amphiphilic macromolecule (CAM)-lipid complexes for efficient siRNA gene
      silencing.
AB  - The accumulated evidence has shown that lipids and polymers each have distinct
      advantages as carriers for siRNA delivery. Composite materials comprising both
      lipids and polymers may present improved properties that combine the advantage of
      each. Cationic amphiphilic macromolecules (CAMs) containing a hydrophobic
      alkylated mucic acid segment and a hydrophilic poly(ethylene glycol) (PEG) tail
      were non-covalently complexed with two lipids, 1,2-dioleoyl-sn-glycero-3
      phosphoethanolamine (DOPE) and 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP),
      to serve as a siRNA delivery vehicle. By varying the weight ratio of CAM to
      lipid, cationic complexes with varying compositions were obtained in aqueous
      media and their properties evaluated. CAM-lipid complex sizes were relatively
      independent of composition, ranging from 100 to 200nm, and zeta potentials varied
      from 10 to 30mV. Transmission electron microscopy confirmed the spherical
      morphology of the complexes. The optimal N/P ratio was 50 as determined by
      electrophoretic mobility shift assay. The ability to achieve gene silencing was
      evaluated by anti-luciferase siRNA delivery to a U87-luciferase cell line.
      Several weight ratios of CAM-lipid complexes were found to have similar delivery
      efficiency compared to the gold standard, Lipofectamine. Isothermal titration
      calorimetry revealed that siRNA binds more tightly at pH=7.4 than pH=5 to CAM
      lipid (1:10 w/w). Further intracellular trafficking studies monitored the siRNA
      escape from the endosomes at 24h following transfection of cells. The findings in
      the paper indicate that CAM-lipid complexes can serve as a novel and efficient
      siRNA delivery vehicle. 

PMID- 24727077
TI  - Prolonged presence of VEGF promotes vascularization in 3D bioprinted scaffolds
      with defined architecture.
AB  - Timely vascularization is essential for optimal performance of bone regenerative
      constructs. Vascularization is efficiently stimulated by vascular endothelial
      growth factor (VEGF), a substance with a short half-life time. This study
      investigates the controlled release of VEGF from gelatin microparticles (GMPs) as
      a means to prolong VEGF activity at the preferred location within 3D bioprinted
      scaffolds, and the effects on subsequent vascularization. The release of VEGF
      from GMPs was continuous for 3 weeks during in vitro studies, and bioactivity was
      confirmed using human endothelial progenitor cells (EPCs) in migration assays.
      Traditional and real-time migration assays showed immediate and efficient EPC
      migration in the presence of GMP-released VEGF, indistinguishable from VEGF
      solution that was added to the medium. Matrigel scaffolds containing EPCs and
      VEGF, which was released either in a fast or sustained fashion by application of
      GMPs, were investigated for their in vivo vasculogenic capacity. Implantation in
      subcutaneous pockets in nude mice for one week demonstrated that vessel formation
      was significantly higher in the VEGF sustained-release group compared to the fast
      release group. In addition, regional differences with respect to VEGF release
      were introduced in 3D bioprinted EPC-laden scaffolds and their influence on
      vasculogenesis was investigated in vivo. The different regions were retained and
      vessel formation occurred analogous with the results seen in the Matrigel plugs.
      We conclude that GMPs are suitable to generate sustained release profiles of
      bioactive VEGF, and that they can be used to create defined differentiation
      regions in 3D bioprinted heterogeneous constructs, allowing a new generation of
      smart scaffold design. The prolonged presence of VEGF led to a significant
      increase in scaffold vascularization when applied in vivo.

PMID- 24727078
TI  - An effectiveness study of individual vs. group cognitive behavioral therapy for
      anxiety disorders in youth.
AB  - OBJECTIVE: Conducted a randomized controlled trial to investigate the
      effectiveness of cognitive behavioral therapy (CBT), and compared the relative
      effectiveness of individual (ICBT) and group (GCBT) treatment approaches for
      anxiety disorders in children and adolescents. METHODS: Referred youth (N = 182,
      M age = 11.5 years, range 8-15 years, 53% girls) with separation anxiety, social
      phobia, or generalized anxiety disorder were randomly assigned to ICBT, GCBT or a
      waitlist control (WLC) in community clinics. Pre-, post-, and one year follow-up
      assessments included youth and parent completed diagnostic interview and symptom
      measures. After comparing CBT (ICBT and GCBT combined) to WLC, ICBT and GCBT were
      compared along diagnostic recovery rates, clinically significant improvement, and
      symptom measures scores using traditional hypothesis tests, as well as
      statistical equivalence tests. RESULTS: Significantly more youth lost all anxiety
      disorders after CBT compared to WLC. Full diagnostic recovery rate was 25.3% for
      ICBT and 20.5% in GCBT, which was not significantly different. There was
      continued lack of significant differences between ICBT and GCBT at one year
      follow-up. However, equivalence between GCBT and ICBT could only be demonstrated
      for clinical severity rating of the principal anxiety disorder and child reported
      anxiety symptoms post-treatment. CONCLUSION: Findings support the effectiveness
      of CBT compared to no intervention for youth with anxiety disorders, with no
      significant differences between ICBT and GCBT. However, the relatively low
      recovery rates highlight the need for further improvement of CBT programs and
      their transportability from university to community settings.

PMID- 24727079
TI  - Development of food intake controls: neuroendocrine and environmental regulation
      of food intake during early life.
AB  - This article is part of a Special Issue "Energy Balance". The development of
      neuroendocrine regulation of food intake during early life has been shaped by
      natural selection to allow for optimal growth and development rates needed for
      survival. In vertebrates, neonates or early larval forms typically exhibit
      "feeding drive," characterized by a developmental delay in 1) responsiveness of
      the hypothalamus to satiety signals (e.g., leptin, melanocortins) and 2)
      sensitivity to environmental cues that suppress food intake. Homeostatic
      regulation of food intake develops once offspring transition to later life
      history stages when growth is slower, neuroendocrine systems are more mature, and
      appetite becomes more sensitive to environmental or social cues. Across
      vertebrate groups, there is a tremendous amount of developmental plasticity in
      both food intake regulation and stress responsiveness depending on the
      environmental conditions experienced during early life history stages or by
      pregnant/brooding mothers. This plasticity is mediated through the organizing
      effects of hormones acting on the food intake centers of the hypothalamus during
      development, which alter epigenetic expression of genes associated with ingestive
      behaviors. Research is still needed to reveal the mechanisms through which
      environmental conditions during development generate and maintain these
      epigenetic modifications within the lifespan or across generations. Furthermore,
      more research is needed to determine whether observed patterns of plasticity are
      adaptive or pathological. It is clear, however, that developmental programming of
      food intake has important effects on fitness, and therefore, has ecological and
      evolutionary implications. 

PMID- 24727081
TI  - Unexpected variation of the codeine/morphine ratio following fatal heroin
      overdose.
AB  - Postmortem samples from 14 cases of suspected heroin overdose were subjected to a
      preliminary systematic toxicological analysis in order to highlight the presence
      of unknown exogenous compounds (e.g., drugs of abuse, alcohol) that may have
      played a role in the mechanism of death. This analysis unveiled histories of poly
      drug use in seven of the cases under investigation. Moreover, the concentrations
      of morphine and codeine in the brain were also investigated, and the results were
      compared with the data obtained from the blood specimens. The concentration of
      morphine in blood ranged from 33 to 688 ng/mL, while the concentration of codeine
      ranged from 0 to 193 ng/mL. However, in the brain, the concentration of morphine
      was found to be between 85 and 396 ng/g, while the levels of codeine ranged from
      11 to 160 ng/g. The codeine/morphine ratio in the blood ranged from 0.043 to
      0.619; however, in the brain, the same ratio was found to be between 0.129 and
      0.552. In most cases, a significantly higher codeine/morphine ratio was found in
      the brain, suggesting the accumulation of codeine in brain tissue due its high
      lipophilicity as compared with morphine. 

PMID- 24727083
TI  - Antimalarial diterpene alkaloids from the seeds of Caesalpinia minax.
AB  - Two new diterpene alkaloids, caesalminines A (1) and B (2), possessing a
      tetracyclic cassane-type furanoditerpenoid skeleton with gamma-lactam ring, were
      isolated from the seeds of Caesalpinia minax. Their structures were determined by
      different spectroscopic methods and ECD calculation. The plausible biosynthetic
      pathway of caesalminines A and B was proposed. The anti-malarial activity of
      compounds 1 and 2 is presented with IC50 values of 0.42 and 0.79 MUM,
      respectively.

PMID- 24727082
TI  - Investigating the interactions of yeast prions: [SWI+], [PSI+], and [PIN+].
AB  - Multiple prion elements, which are transmitted as heritable protein conformations
      and often linked to distinct phenotypes, have been identified in the budding
      yeast, Saccharomyces cerevisiae. It has been shown that overproduction of a prion
      protein Swi1 can promote the de novo conversion of another yeast prion [PSI(+)]
      when Sup35 is co-overproduced. However, the mechanism underlying this Pin(+)
      ([PSI(+)] inducible) activity is not clear. Moreover, how the Swi1 prion
      ([SWI(+)]) interacts with other yeast prions is unknown. Here, we demonstrate
      that the Pin(+) activity associated with Swi1 overproduction is independent of
      Rnq1 expression or [PIN(+)] conversion. We also show that [SWI(+)] enhances the
      appearance of [PSI(+)] and [PIN(+)]. However, [SWI(+)] significantly compromises
      the Pin(+) activity of [PIN(+)] when they coexist. We further demonstrate that a
      single yeast cell can harbor three prions, [PSI(+)], [PIN(+)], and [SWI(+)],
      simultaneously. However, under this condition, [SWI(+)] is significantly
      destabilized. While the propensity to aggregate underlies prionogenesis, Swi1 and
      Rnq1 aggregates resulting from overproduction are usually nonheritable.
      Conversely, prion protein aggregates formed in nonoverexpressing conditions or
      induced by preexisting prion(s) are more prionogenic. For [PSI(+)] and [PIN(+)]
      de novo formation, heterologous "facilitators," such as preexisting [SWI(+)]
      aggregates, colocalize only with the newly formed ring-/rod-shaped Sup35 or Rnq1
      aggregates, but not with the dot-shaped mature prion aggregates. Their
      colocalization frequency is coordinated with their prion inducibility, indicating
      that prion-prion interactions mainly occur at the early initiation stage. Our
      results provide supportive evidence for the cross-seeding model of prionogenesis
      and highlight a complex interaction network among prions in yeast.

PMID- 24727084
TI  - New triterpenic acids from Uncaria rhynchophylla: chemistry, NO-inhibitory
      activity, and tandem mass spectrometric analysis.
AB  - Five new oleanane and ursane type triterpenes, namely uncarinic acids F-J (1-5),
      together with six known triterpenic acids (6-11) were isolated from the stems and
      hooks of Uncaria rhynchophylla. Structure elucidation of 1-5 was based on the
      integrated analyses of high-resolution MS data, 1D ((1)H NMR, (13)C NMR, DEPT)
      and 2D (HSQC, HMBC, ROESY) NMR spectra. Compounds 4, 10, and 11 exhibited weak
      inhibitory effects on LPS-induced NO production in RAW264.7 cells (with IC50
      1.48, 7.01, and 1.89 MUM, respectively) with dexamethasone (IC50 0.04 MUM) and
      quercetin (IC50 0.86 MUM) as the positive controls. 19-OH substituted oleanane
      triterpenic acids (1, 2, 5, 8) were prone to eliminate CH2O3, whereas those
      ursane-type encompassing 19-OH (3, 6, 7, 9, 4) were featured by preferred
      cleavage of H2O while performing the negative collision-induced MS/MS
      fragmentation on an LTQ/Orbitrap mass spectrometer.

PMID- 24727080
TI  - Understanding the control of ingestive behavior in primates.
AB  - This article is part of a Special Issue "Energy Balance". Ingestive behavior in
      free-ranging populations of nonhuman primates is influenced by resource
      availability and social group organization and provides valuable insight on the
      evolution of ecologically adaptive behaviors and physiological systems. As
      captive populations were established, questions regarding proximate mechanisms
      that regulate food intake in these animals could be more easily addressed. The
      availability of these captive populations has led to the use of selected species
      to understand appetite control or metabolic physiology in humans. Recognizing the
      difficulty of quantitating food intake in free-ranging groups, the use of
      captive, singly-housed animals provided a distinct advantage though, at the same
      time, produced a different social ecology from the animals' natural habitat.
      However, the recent application of novel technologies to quantitate caloric
      intake and energy expenditure in free-feeding, socially housed monkeys permits
      prospective studies that can accurately define how food intake changes in
      response to any number of interventions in the context of a social environment.
      This review provides an overview of studies examining food intake using captive
      nonhuman primates organized into three areas: a) neurochemical regulation of food
      intake in nonhuman primates; b) whether exposure to specific diets during key
      developmental periods programs differences in diet preferences or changes the
      expression of feeding related neuropeptides; and c) how psychosocial factors
      influence appetite regulation. Because feeding patterns are driven by more than
      just satiety and orexigenic signals, appreciating how the social context
      influences pattern of feeding in nonhuman primates may be quite informative for
      understanding the biological complexity of feeding in humans. 

PMID- 24727085
TI  - The laxative effect of emodin is attributable to increased aquaporin 3 expression
      in the colon of mice and HT-29 cells.
AB  - Emodin (1,3,8-trihydroxy-6-methylanthraquinone) is a stimulant laxative and used
      to treat constipation. Aquaporin 3 (AQP3) plays an important role in regulating
      water transfer in the colon. In the study, we investigated whether the laxative
      effect of emodin is associated with the regulation of AQP3 in the colon. Our
      results showed that treatment with emodin increased the fecal water content in
      the colon of mice and evaluation index of defecation in a dose-dependent manner.
      More interestingly, emodin significantly increased the AQP3 protein and mRNA
      expression both in the colon of mice and in human intestinal epithelial cells (HT
      29). Mechanistically, emodin obviously up-regulated the cyclic adenosine
      monophosphate (cAMP)-dependent protein kinase A catalytic subunits alpha (PKA C
      alpha) and phosphorylated cAMP response element-binding protein (p-CREB Ser133)
      expression in HT-29 cells. These results suggest that the laxative effect of
      emodin is associated with the increased expression of AQP3 by up-regulating PKA/p
      CREB signal pathway. 

PMID- 24727086
TI  - Antibacterial activity of essential oils, their blends and mixtures of their main
      constituents against some strains supporting livestock mastitis.
AB  - Ten of the most known and used commercial essential oils (Cinnamomum zeylanicum
      L., Citrus bergamia Risso, Eucalyptus globulus Labill., Foeniculum vulgare Mill.,
      Origanum majorana L., Origanum vulgare L., Rosmarinus officinalis L., Satureja
      montana L., Thymus vulgaris L. ct. carvacrol, Thymus vulgaris L. ct. thymol) were
      tested against six bacteria strains Staphylococcus aureus, Staphylococcus
      chromogenes, Staphylococcus sciuri, Staphylococcus warneri, Staphylococcus
      xylosus and Escherichia coli, responsible for mastitis in animals. The best
      results were achieved by S. montana, T. vulgaris ct. thymol and O. vulgare. Two
      binary mixtures of essential oils (EOs) were prepared of S. montana and T.
      vulgaris ct. thymol (ST) and of S. montana and O. vulgare (SO). The ST mixture
      exhibited the best inhibitory activity against all the tested bacterial strains.
      Two artificial mixtures of carvacrol/thymol (AB) and carvacrol/thymol/p-cymene
      (CD) were prepared and tested against all of the bacterial strains used. The
      results exhibited a general reduction of the inhibitory activity of mixture AB,
      although not reaching the inhibition of the ST and SO mixtures. However the
      mixture CD presented an apparent strong inhibition against S. aureus and S.
      sciuri. The EO mixtures and the mixture CD represent promising phytotherapic
      approaches against bacteria strains responsible for environmental mastitis. 

PMID- 24727087
TI  - Role of budesonide in liver transplantation.

PMID- 24727088
TI  - Expression of the tissue inhibitor of metalloproteinase-3 by transplanted VSMCs
      modifies heart structure and function after myocardial infarction.
AB  - OBJECTIVES: Extracellular matrix (ECM) remodelling is a critical aspect of
      cardiac remodelling following myocardial infarction. Tissue inhibitors of
      metalloproteinases (TIMPs) are physiological inhibitors of matrix
      metalloproteinases (MMPs) that degrade the ECM proteins. TIMP-3 is highly
      expressed in the heart and is markedly downregulated in patients with ischaemic
      cardiomyopathy. Cell-based gene therapy can enhance the effects of cell
      transplantation by temporally and spatially regulating the release of the gene
      product. The purpose of this study was to investigate the role of TIMP-3 gene
      transfected vascular smooth muscle cells (VSMCs) in modifying heart structure and
      function in rats when transplanted 3days after myocardial infarction (MI).
      METHODS: Anesthetised rats were subjected to coronary artery ligation followed
      3days later by thoracotomy and transplantation of TIMP-3 gene-transfected VSMCs,
      untransfected VSMCs or medium injected directly into the ischaemic myocardium. We
      assessed left ventricular structure and function by echocardiography and
      morphometry, and measured the levels of myocardial matrix metalloproteinase-2 and
      -9 (MMP-2, MMP-9), TIMP-3 and tumour necrosis factor-alpha (TNF-alpha) at 4weeks
      post-myocardial infarction. RESULTS: Transplantation of TIMP-3 gene-transfected
      VSMCs and untransfected VSMCs significantly decreased scar expansion and
      ventricular dilatation 25days post-transplantation (4weeks after MI). MMPs and
      TNF-alpha levels were reduced in the transplantation groups when compared to the
      group that was given an injection of medium only. Transplantation of TIMP-3 gene
      transfected VSMCs was more effective in preventing progressive cardiac
      dysfunction, ventricular dilatation and in reducing MMP-2, MMP-9 and TNF-alpha
      levels when compared to the transplantation of untransfected VSMCs. CONCLUSIONS:
      TIMP-3 gene transfection was associated with attenuated left ventricular dilation
      and recovery of systolic function after MI compared with the control. TIMP-3
      transfection enhanced the effects of transplanted VSMCs in rats by inhibiting
      matrix degradation and inflammatory cytokine expression, leading to improved
      myocardial remodelling.

PMID- 24727089
TI  - Rabbit anti-T-lymphocyte globulin (ATG) persists with differential reactivity in
      patients' sera after full hematopoetic regeneration from allogeneic stem cell
      transplantation.
AB  - BACKGROUND: Rabbit polyclonal anti-T-lymphocyte Globulin (ATG-F(r), Fresenius) is
      widely used for GvHD prophylaxis in allogeneic stem cell transplantation (SCT).
      ATG has a wide epitope spectrum and has been shown to react with all compartments
      of peripheral blood mononuclear cells (PBMNCs). ATG induces apoptosis in all
      cellular compartments. In this study we investigated the binding of ATG in sera
      from ten patients treated with rabbit ATG to PBMNCs and subcellular compartments
      after full hematopoetic regeneration on day 21 post SCT. METHODS: Sera from ten
      patients treated with unrelated donor allogeneic SCT for hematologic malignancy
      were collected after full hematopoetic regeneration on day 21 post SCT and
      incubated with healthy donor PBMNCs. Rabbit ATG on PBMNCs was detected by
      staining with fluorochrome labeled anti-rabbit IgG antibody. PBMNC compartments
      were investigated by counterstaining with lineage markers CD4, CD8, CD14 CD20 and
      CD56. Positive control was the fresh ATG preparation. RESULTS: We found that
      patient's' sera retained activity towards PBMNCs in all patients, yet at reduced
      intensity. When cell compartments were analyzed we found a differential pattern
      of ATG reactivity within sera. The mean percentage of total cells reacting with
      serum ATG from ten patients compared to fresh ATG (100%) was 44% of CD4 positive
      and 58% of CD8 positive T-lymphocytes, 41% of CD56 positive NK-cells, 83% of CD20
      positive B-lymphocytes and 98% of CD14 positive monocytes. However, inter
      individual variations were high with a wide spread around the mean especially for
      T-lymphocytes. CONCLUSION: We conclude that upon PBMNC regeneration following SCT
      and immunosuppressive treatment with ATG subpopulations of T-lymphocytes (CD4,
      CD8) and NK cells (CD56) are selected that lose epitopes recognized by ATG while
      B-lymphocytes (CD20) and monocytes (CD14) maintain a homogeneity with respect to
      epitopes recognized by ATG. This may be due to loss of idiotypes reacting with
      subpopulations of high frequency and turnover. Further studies should investigate
      the subphenotype of these populations and functional effects of extremely high or
      low reactivity with one or more compartments in some patients on GvHD and disease
      outcome.

PMID- 24727090
TI  - Population genetics of Cryptosporidium meleagridis in humans and birds: evidence
      for cross-species transmission.
AB  - Population genetic studies have been used to understand the transmission of
      pathogens in humans and animals, especially the role of zoonotic infections and
      evolution and dispersal of virulent subtypes. In this study, we analysed the
      genetic diversity and population structure of Cryptosporidium meleagridis, the
      only known Cryptosporidium species that infects both avian and mammalian hosts
      and is responsible for approximately 10% of human cryptosporidiosis in some
      areas. A total of 62 C. meleagridis specimens from children, AIDS patients, and
      birds in Lima, Peru were characterised by sequence analysis of the ssrRNA gene
      and five minisatellite, microsatellite and polymorphic markers in chromosome 6,
      including the 60 kDa glycoprotein (gp60), 47 kDa glycoprotein (CP47), a serine
      repeat antigen (MSC6-5), retinitis pigmentosa GTPase regulator (RPGR) and
      thrombospondin protein 8 (TSP8). The multilocus sequence analysis identified
      concurrent infections with Cryptosporidium hominis in four AIDS patients and
      three children. Unique subtypes of C. meleagridis ranged from eight at the gp60
      locus (gene diversity -Hd=0.651), three at the RPGR (Hd=0.556), three at the MSC6
      5 locus (Hd=0.242), two at TSP8 (Hd=0.198), to one at CP47 (monomorphic), much
      lower than that of C. hominis in the same area. Intragenic linkage disequilibrium
      was strong and complete at all gene loci. Intergenic linkage disequilibrium was
      highly significant (P<0.001) for all pairs of polymorphic loci. Two major groups
      of subtypes were seen, with most subtypes belonging to group 1. Within group 1,
      there was no clear population segregation, and two of the 14 multilocus subtypes
      of C. meleagridis were found in both AIDS patients and birds. We believe that
      these results provide the first evidence of a clonal population structure of C.
      meleagridis and the likely occurrence of cross-species transmission of C.
      meleagridis between birds and humans.

PMID- 24727091
TI  - Natural killer cell intrinsic toll-like receptor MyD88 signaling contributes to
      IL-12-dependent IFN-gamma production by mice during infection with Toxoplasma
      gondii.
AB  - Myeloid differentiation factor 88 (MyD88)-dependent IL-12 secretion by dendritic
      cells is critical for natural killer cell-mediated IFN-gamma production and
      innate resistance to Toxoplasma gondii. Although MyD88(-/-) mice challenged with
      T. gondii have defective IL-12 responses and succumb to infection, administration
      of IL-12 to MyD88(-/-) mice fails to prevent acute mortality, suggesting that
      MyD88 may mediate signals within natural killer cells important for IL-12
      dependent IFN-gamma production and innate resistance to this parasite. In this
      study, we found that T. gondii antigens and IL-12 could synergistically trigger
      IFN-gamma secretion by natural killer cells, which was dependent on toll-like
      receptor-MyD88 signaling. Further analysis showed that p38 mitogen-activated
      protein kinase, extracellular signal-regulated kinase, c-Jun N-terminal kinase
      and NF-kappaB multiple pathways downstream of MyD88 contributed to IFN-gamma
      production by natural killer cells. Moreover, the well-established toll-like
      receptor agonists, T. gondii profilin (Tgprofilin) and T. gondii heat shock
      protein 70 (TgHSP70) could evoke a similar IFN-gamma secretory response in
      natural killer cells to that evoked by T. gondii antigens. In vivo adoptive
      transfer experiments showed that, upon challenge with T. gondii, NOD/SCID-beta2
      microglobulin null (NOD/SCID-beta2m(-/-)) mice injected i.v. with MyD88(-/-)
      natural killer cells had reduced serum IFN-gamma levels and increased splenic
      tachyzoite burdens compared with those injected i.v. with wild-type natural
      killer cells. Taken together, these findings demonstrate a critical role for
      natural killer cell intrinsic toll-like receptor-MyD88 signaling in IL-12
      dependent early IFN-gamma production and innate resistance to T. gondii. 

PMID- 24727092
TI  - MicroRNAs as regulators and mediators of c-MYC function.
AB  - In the past ten years microRNAs (miRNAs) have been widely implicated as
      components of tumor suppressive and oncogenic pathways. Also the proto-typic
      oncogene c-MYC has been connected to miRNAs. The c-MYC gene is activated in
      approximately half of all tumors, and its product, the c-MYC transcription
      factor, regulates numerous processes e.g. cell cycle progression, metabolism,
      epithelial-mesenchymal transition (EMT), metastasis, stemness, and angiogenesis,
      thereby facilitating tumor initiation and progression. c-MYC target-genes, which
      mediate these functions of c-MYC, represent a complex network of protein- and non
      coding RNAs, including numerous miRNAs. For example, c-MYC directly regulates
      expression of the miR-17-92 cluster, miR-34a, miR-15a/16-1 and miR-9. Moreover,
      the expression and activity of c-MYC itself are under the control of miRNAs.
      Here, we survey how these networks mediate and regulate c-MYC functions. In the
      future, miRNAs connected to c-MYC may be used for diagnostic and therapeutic
      approaches. This article is part of a Special Issue entitled: Myc proteins in
      cell biology and pathology. 

PMID- 24727093
TI  - Single-molecule studies of riboswitch folding.
AB  - The folding dynamics of riboswitches are central to their ability to modulate
      gene expression in response to environmental cues. In most cases, a structural
      competition between the formation of a ligand-binding aptamer and an expression
      platform (or some other competing off-state) determines the regulatory outcome.
      Here, we review single-molecule studies of riboswitch folding and function,
      predominantly carried out using single-molecule FRET or optical trapping
      approaches. Recent results have supplied new insights into riboswitch folding
      energy landscapes, the mechanisms of ligand binding, the roles played by divalent
      ions, the applicability of hierarchical folding models, and kinetic vs.
      thermodynamic control schemes. We anticipate that future work, based on improved
      data sets and potentially combining multiple experimental techniques, will enable
      the development of more complete models for complex RNA folding processes. This
      article is part of a Special Issue entitled: Riboswitches.

PMID- 24727094
TI  - Early results of Massachusetts healthcare reform on racial, ethnic, and
      socioeconomic disparities in cardiovascular care.
AB  - BACKGROUND: Insured adults receive invasive cardiovascular procedures more
      frequently than uninsured adults. We examined the impact of healthcare reform in
      Massachusetts on use of coronary revascularization procedures and in-hospital and
      1-year mortality by race/ethnicity, education, and sex. METHODS AND RESULTS:
      Using hospital claims data, we compared differences in coronary revascularization
      rates (coronary artery bypass grafting or percutaneous coronary intervention) and
      in-hospital mortality by race/ethnicity, education, and sex among Massachusetts
      residents aged 21 to 64 years hospitalized with a principal discharge diagnosis
      of ischemic heart disease before (November 1, 2004, to July 31, 2006) and after
      (December 1, 2006, to September 30, 2008) reform; 1-year mortality was calculated
      for those undergoing revascularization. Adjusted logistic regression assessed 24
      216 discharges before reform and 20 721 discharges after reform. Blacks had 30%
      lower odds of receiving coronary revascularization than whites in the prereform
      period. Compared with whites in the postreform period, blacks (odds ratio=0.73;
      95% confidence interval, 0.63-0.84) and Hispanics (odds ratio= 0.84; 95%
      confidence interval, 0.74-0.97) were less likely and Asians (odds ratio=1.29; 95%
      confidence interval, 1.01-1.65) were more likely to receive coronary
      revascularization. Patients living in more educated communities, men, and persons
      with private insurance were more likely to receive coronary revascularization
      before and after reform. Compared with the prereform period, the adjusted odds of
      in-hospital mortality were higher in patients living in less-educated communities
      in the postreform period. No differences in 1-year mortality by race/ethnicity,
      education, or sex for revascularized patients were observed before or after
      reform. CONCLUSIONS: Reducing insurance barriers to receipt of coronary
      revascularization procedures has not yet eliminated preexisting demographic and
      educational disparities in access to these procedures.

PMID- 24727095
TI  - Alterations in cerebellar physiology are associated with a stiff-legged gait in
      Atcay(ji-hes) mice.
AB  - Recent evidence suggests that dystonia, a movement disorder characterized by
      sustained involuntary muscle contractions, can be associated with cerebellar
      abnormalities. The basis for how functional changes in the cerebellum can cause
      dystonia is poorly understood. Here we identify alterations in physiology in
      Atcay(ji-hes) mice which in addition to ataxia, have an abnormal gait with hind
      limb extension and toe walking, reminiscent of human dystonic gait. No
      morphological abnormalities in the brain accompany the dystonia, but partial
      cerebellectomy causes resolution of the stiff-legged gait, suggesting that
      cerebellar dysfunction contributes to the dystonic gait of Atcay(ji-hes) mice.
      Recordings from Purkinje and deep cerebellar nuclear (DCN) neurons in acute brain
      slices were used to determine the physiological correlates of dystonia in the
      Atcay(ji-hes) mice. Approximately 50% of cerebellar Purkinje neurons fail to
      display the normal repetitive firing characteristic of these cells. In addition,
      DCN neurons exhibit increased intrinsic firing frequencies with a subset of
      neurons displaying bursts of action potentials. This increased intrinsic
      excitability of DCN neurons is accompanied by a reduction in after
      hyperpolarization currents mediated by small-conductance calcium-activated
      potassium (SK) channels. An activator of SK channels reduces DCN neuron firing
      frequency in acute cerebellar slices and improves the dystonic gait of Atcay(ji
      hes) mice. These results suggest that a combination of reduced Purkinje neuron
      activity and increased DCN intrinsic excitability can result in a combination of
      ataxia and a dystonia-like gait in mice.

PMID- 24727096
TI  - Multiple system atrophy: a prototypical synucleinopathy for disease-modifying
      therapeutic strategies.
AB  - Despite active fundamental, translational and clinical research, no therapeutic
      intervention has yet shown convincing effects on disease progression in
      Parkinson's disease (PD) patients. Indeed, several disease-modification trials
      failed or proved to be inconclusive due to lack of consistency between clinical
      rating scales and putative surrogate markers of disease progression, or
      confounding symptomatic effects of the tested compound. Multiple system atrophy
      (MSA) is a rapidly progressing orphan disorder leading to severe motor disability
      within a few years. Together with PD and dementia with Lewy bodies (DLB), MSA
      belongs to the synucleinopathies, a group of neurodegenerative disorders
      characterized by the abnormal accumulation of alpha-synuclein. Crucial milestones
      have been reached for successfully conducting clinical intervention trials in a
      large number of patients with MSA. In this personal view, we will review
      evidence, and discuss why MSA could prove the most relevant clinical model for
      assessing treatments that target mechanisms operating in all synucleinopathies.

PMID- 24727097
TI  - Peptidomic analysis of the neurolysin-knockout mouse brain.
AB  - A large number of intracellular peptides are constantly produced following
      protein degradation by the proteasome. A few of these peptides function in cell
      signaling and regulate protein-protein interactions. Neurolysin (Nln) is a
      structurally defined and biochemically well-characterized endooligopeptidase, and
      its subcellular distribution and biological activity in the vertebrate brain have
      been previously investigated. However, the contribution of Nln to peptide
      metabolism in vivo is poorly understood. In this study, we used quantitative mass
      spectrometry to investigate the brain peptidome of Nln-knockout mice. An
      additional in vitro digestion assay with recombinant Nln was also performed to
      confirm the identification of the substrates and/or products of Nln. Altogether,
      the data presented suggest that Nln is a key enzyme in the in vivo degradation of
      only a few peptides derived from proenkephalin, such as Met-enkephalin and
      octapeptide. Nln was found to have only a minor contribution to the intracellular
      peptide metabolism in the entire mouse brain. However, further studies appear
      necessary to investigate the contribution of Nln to the peptide metabolism in
      specific areas of the murine brain. BIOLOGICAL SIGNIFICANCE: Neurolysin was first
      identified in the synaptic membranes of the rat brain in the middle 80's by
      Frederic Checler and colleagues. Neurolysin was well characterized biochemically,
      and its brain distribution has been confirmed by immunohistochemical methods. The
      neurolysin contribution to the central and peripheral neurotensin-mediated
      functions in vivo has been delineated through inhibitor-based pharmacological
      approaches, but its genuine contribution to the physiological inactivation of
      neuropeptides remains to be firmly established. As a result, the main
      significance of this work is the first characterization of the brain peptidome of
      the neurolysin-knockout mouse. This article is part of a Special Issue entitled:
      Proteomics, mass spectrometry and peptidomics, Cancun 2013. Guest Editors: Cesar
      Lopez-Camarillo, Victoria Pando-Robles and Bronwyn Jane Barkla.

PMID- 24727098
TI  - Preventive and therapeutic potential of peptides from cereals against cancer.
AB  - Epidemiological studies have shown that regular consumption of food based on
      whole-grain cereals and their products is associated with reduced risks of
      various types of degenerative chronic diseases. Food proteins are considered an
      important source of nutraceutical peptides and amino acids that can exert
      biological functions to promote health and prevent disease, including cancer.
      There have been several reports on peptides with anti-tumour activity in recent
      years. Plant-derived peptides, such as rapeseed, amaranth and soybean lunasin
      have received main attention. In this review, we extend this vision to analyse
      the evidence of current advances in peptides in cereals such as wheat, maize,
      rice, barley, rye and pseudocereals compared with soybean. We also show evidence
      of several mechanisms through which bioactive peptide exerts anti-tumour
      activity. Finally, we report the current status of major strategies for the
      fractionation, isolation and characterisation of bioactive peptides in cereals.
      BIOLOGICAL SIGNIFICANCE: In recent reports, it has been shown that peptides are
      an interesting alternative in the search for new treatments for cancer. One of
      the most studied sources of these peptides is food proteins; however, a review
      that includes more recent findings for cereals as a potential source of bioactive
      peptides in the treatment of cancer, the techniques for their isolation and
      characterisation and the assays used to prove their bioactivity is not available.
      This review can be used as a tool in the search for new sources of anti-cancer
      peptides. The authors have no conflicts of interest, financial or otherwise.

PMID- 24727099
TI  - The mitochondrial lysine acetylome of Arabidopsis.
AB  - Posttranslational modifications are essential regulators of protein functions as
      they can modify enzyme activities or protein-molecule interactions by changing
      the charge state or chemical properties of their target amino acid. The acetyl
      moiety of the central energy metabolite acetyl-CoA can be transferred to the
      epsilon-amino group of lysine, a process known as lysine acetylation which is
      implicated in the regulation of key metabolic enzymes in various organisms. Since
      plant mitochondria are of great importance for plant growth and development and
      as they house key enzymes of oxidative phosphorylation and photorespiration, it
      is essential to investigate the occurrence of lysine acetylation in this
      organelle. Here we characterised the plant mitochondrial acetylome of Arabidopsis
      mitochondria by LC-MS/MS analysis. In total 120 lysine-acetylated mitochondrial
      proteins containing 243 acetylated sites were identified. These proteins were
      mapped into functional categories showing that many proteins with essential
      functions from the tricaboxylic cycle and the respiratory chain are lysine
      acetylated, as well as proteins involved in photorespiration, amino acid and
      protein metabolism, and redox regulation. Immuno-detection of mitochondrial
      proteins revealed that many lysine-acetylated proteins reside in native protein
      complexes. Furthermore, in vitro experiments demonstrated that lysine acetylation
      can occur non-enzymatically in Arabidopsis mitochondria at physiological matrix
      pH. 

PMID- 24727100
TI  - Overcoming challenges to effectiveness of mobile markets in US food deserts.
AB  - The purpose of this research is to investigate whether mobile food markets may be
      effective in facilitating healthy food choices in food deserts. We investigate
      who does and does not use mobile food markets and why, and whether mobile markets
      have the potential to alter attitudes and food choices, and if so, how? We use a
      focus group study at four sites in the US to ask groups of mobile market shoppers
      and non-shoppers about their shopping, cooking, and eating attitudes and
      behaviors. We find that mobile market shoppers eat significantly more servings of
      fruits and vegetables, however, both shoppers and non-shoppers perceive fruits
      and vegetables as luxury items, and both groups lack knowledge about what is a
      serving and what is the recommended number of servings per day. Both groups
      identified the following needs for mobile markets to be more successful:
      increased awareness and advertising; affordability; improved convenience by
      offering more stops and hours, as well as greater variety of items for one-stop
      shopping; emphasis on value and service; and building trust within communities. 

PMID- 24727101
TI  - Food parenting practices and child dietary behavior. Prospective relations and
      the moderating role of general parenting.
AB  - Research on parenting practices has focused on individual behaviors while largely
      failing to consider the context of their use, i.e., general parenting. We
      examined the extent to which food parenting practices predict children's dietary
      behavior (classified as unhealthy: snacking, sugar-sweetened beverage; and
      healthy: water and fruit intake). Furthermore, we tested the moderating role of
      general parenting on this relationship. Within the KOALA Birth Cohort Study, in
      the Netherlands, questionnaire data were collected at 6 and 8 years (N = 1654).
      Correlations were computed to assess the association between food parenting
      practices and general parenting (i.e., nurturance, behavioral control, structure,
      coercive control, and overprotection). Linear regression models were fitted to
      assess whether food parenting practices predict dietary behavior. Instrumental
      and emotional feeding, and pressure to eat were found to have associations with
      undesirable child dietary behavior (increased unhealthy intake/decreased healthy
      intake), whereas associations were in the desirable direction for covert control,
      encouragement and restriction. Moderation analyses were performed by evaluating
      interactions with general parenting. The associations of encouragement and covert
      control with desirable child dietary behaviors were found to be stronger for
      children who were reared in a positive parenting context. Future research should
      assess the influence of contextual parenting factors moderating the relationships
      between food parenting and child dietary behavior as the basis for the
      development of more effective family-based interventions.

PMID- 24727102
TI  - Efforts to overcome vegetarian-induced dissonance among meat eaters.
AB  - Meat eaters face dissonance whether it results from inconsistency ("I eat meat; I
      don't like to hurt animals"), aversive consequences ("I eat meat; eating meat
      harms animals"), or threats to self image ("I eat meat; compassionate people
      don't hurt animals"). The present work proposes that there are a number of
      strategies that omnivores adopt to reduce this dissonance including avoidance,
      dissociation, perceived behavioral change, denial of animal pain, denial of
      animal mind, pro-meat justifications, reducing perceived choice, and actual
      behavioral change. The presence of vegetarians was speculated to cause meat
      eating to be a scrutinized behavior, remind meat eaters of their discomfort, and
      undermine the effectiveness of these strategies. It was therefore hypothesized
      that exposure to a description of a vegetarian would lead omnivores to embrace
      dissonance-reducing strategies. Supporting this hypothesis, participants who read
      a vignette about a vegetarian denied animal mind more than participants who read
      about a gluten-free individual. It was also hypothesized that omnivores would be
      sensitive to individual differences between vegetarians and would demonstrate
      using dissonance-reducing strategies more when the situation failed to provide
      cognitions consonant with eating meat or to reduce dissonant cognitions. Four
      experiments supported this prediction and found that authentic vegetarians,
      vegetarians freely making the decision to abandon meat, consistent vegetarians,
      and anticipating moral reproach from vegetarians produced greater endorsement of
      dissonance-reducing strategies than their counterpart conditions. 

PMID- 24727105
TI  - Body image for pelvic organ prolapse - a new important questionnaire has come.

PMID- 24727104
TI  - GSPE is superior to NAC in the prevention of contrast-induced nephropathy: might
      this superiority be related to caspase 1 and calpain 1?
AB  - AIMS: Our study was intended to evaluate the role of inducible nitric oxide
      synthase (iNOS), endothelial nitric oxide synthase (eNOS), caspases 1 and 3 and
      calpain 1 in the pathogenesis of contrast-induced nephropathy (CIN) and to
      compare the protective effects of N acetyl cysteine (NAC) and grape seed
      proanthocyanidin extract (GSPE) against the development of CIN. MAIN METHODS: 32
      rats were divided into four groups; control, contrast media (CM), CM+NAC and
      CM+GSPE. CIN was induced by administration of 7 ml/kg diatrizoate. The experiment
      was discontinued on the ninth day. Blood was collected for blood urea nitrogen
      (BUN) and creatinine measurement. Rat kidney tissues were removed for
      histopathological evaluation and the investigation of caspases 1 and 3, iNOS,
      eNOS, TUNEL and calpain 1. KEY FINDINGS: A significant increase in BUN,
      creatinine, renal histopathological injury, TUNEL, caspases 1, 3, calpain 1, iNOS
      and eNOS was observed in the CM group compared to the control group. There was
      amelioration in all these parameters in the CM+GSPE group, while there was no
      significant amelioration in BUN, creatinine and renal histopathological injury in
      the CM+NAC group. In addition, calpain 1 staining and creatinine were
      significantly lower in the CM+GSPE group compared to the CM+NAC group.
      SIGNIFICANCE: Our study showed, for the first time in the literature, that GSPE
      has a greater renoprotective effect compared with NAC and that this effective
      protection may be related to decrease in calpain 1 levels.

PMID- 24727103
TI  - Nouns, verbs, objects, actions, and abstractions: local fMRI activity indexes
      semantics, not lexical categories.
AB  - Noun/verb dissociations in the literature defy interpretation due to the confound
      between lexical category and semantic meaning; nouns and verbs typically describe
      concrete objects and actions. Abstract words, pertaining to neither, are a
      critical test case: dissociations along lexical-grammatical lines would support
      models purporting lexical category as the principle governing brain organisation,
      whilst semantic models predict dissociation between concrete words but not
      abstract items. During fMRI scanning, participants read orthogonalised word
      categories of nouns and verbs, with or without concrete, sensorimotor meaning.
      Analysis of inferior frontal/insula, precentral and central areas revealed an
      interaction between lexical class and semantic factors with clear category
      differences between concrete nouns and verbs but not abstract ones. Though the
      brain stores the combinatorial and lexical-grammatical properties of words, our
      data show that topographical differences in brain activation, especially in the
      motor system and inferior frontal cortex, are driven by semantics and not by
      lexical class. 

PMID- 24727106
TI  - Reply: To PMID 24631437.

PMID- 24727107
TI  - Structure of the O-polysaccharide from the lipopolysaccharide of Providencia
      alcalifaciens O33.
AB  - Mild acid degradation of the lipopolysaccharide from Providencia alcalifaciens
      O33 resulted in an O-polysaccharide along with core and O-unit-bearing core
      oligosaccharides. Composition of the oligosaccharides was inferred by ESI mass
      spectrometry. Based on sugar and methylation analyses, Smith degradation and (1)H
      and (13)C NMR spectroscopy data, the following structure of the tetrasaccharide O
      unit of the O-polysaccharide was established: Another O-polysaccharide structure
      has been reported earlier for Providencia stuartii O33 but later found to belong
      to a P. stuartii O52 strain. 

PMID- 24727108
TI  - Contributions of South American research centers to Carbohydrate Research.
AB  - The present article shows the objective figures of the contributions of South
      American research centers to Carbohydrate Research during its 50years of history,
      measured in terms of members of the Editorial Board, number of articles and
      citations to them, together with a country-based comparison, and the progression
      of these contributions with time. In addition, it also shows the subjective
      feelings of the author toward the same journal.

PMID- 24727109
TI  - Spicing up the military: Use and effects of synthetic cannabis in substance
      abusing army personnel.
AB  - Synthetic cannabis (SC) use has been increasing within the United States. Due to
      difficulties with its detection through standard testing, it may be an attractive
      substance of abuse for military personnel. However, few studies have examined the
      consequences of its use in this population, including evidence for its potential
      for abuse and dependence. Participants included 368 active-duty Army personnel
      who expressed interest in participating in a "check-up" around their alcohol or
      substance use, of whom 294 (80%) met DSM-IV criteria for substance abuse or
      dependence (including alcohol, illicit drugs, and prescription medications) and
      were not engaged in substance abuse treatment. Forty-one participants (11%)
      reported using SC in the last 90 days. Of those, 27 listed SC as their drug of
      choice. There were no significant differences in race, ethnicity, deployment
      history, or religion between SC users and others. Users of SC were generally
      younger and had less education and income than those who used only alcohol. Among
      SC users, 12% met criteria for drug abuse and 68% for dependence. Participants
      perceived SC use to be significantly more prevalent among military personnel than
      among civilians. Results suggest that SC is prevalent among substance-using
      soldiers and that DSM-IV criteria for abuse and dependence apply to SC. In
      addition, results highlight the importance of assessing and treating SC use among
      active-duty military personnel.

PMID- 24727110
TI  - Smoking, nicotine dependence and nicotine intake by socio-economic status and
      marital status.
AB  - INTRODUCTION: Low socio-economic status (SES) is strongly related to smoking, but
      studies examining the association of SES with nicotine dependence (ND) are
      scarce. The aim of this study was to examine the associations of SES and marital
      status with smoking, multiple measures of ND, and cotinine as a nicotine intake
      biomarker. METHODS: The sample comprised 1746 ever smokers, sampled from the
      National FINRISK 2007 Study, who had completed a tobacco specific questionnaire
      in addition to the standard clinical examination. The Fagerstrom Test for
      Nicotine Dependence (FTND), the Heaviness of Smoking Index (HSI), the Nicotine
      Dependence Syndrome Scale (NDSS), and the Hooked On Nicotine Checklist (HONC)
      were assessed, while plasma cotinine was measured as a biomarker of nicotine
      exposure in daily smokers. Univariate and multivariate associations were assessed
      by linear regression and multinomial logistic regression. RESULTS: In
      multivariate models, lower education was associated with higher FTND and HSI,
      income with HSI, and occupation with HSI (men only), FTND, HONC and NDSS scores.
      Lower education was related to higher cotinine levels among daily smokers,
      although the association diminished slightly after adjusting for daily smoking
      amount. Living without a spouse was associated with daily smoking and higher ND.
      CONCLUSION: In this cross-sectional study low SES was linked with higher ND among
      current smokers, while low SES was associated with higher cotinine levels among
      daily smokers. Living alone was linked with higher ND. Longitudinal studies are
      warranted to further explore these associations. As lower SES smokers are more
      addicted they may need more targeted cessation services to succeed in quitting
      smoking.

PMID- 24727111
TI  - Development of a self-report format of ASSIST with university students.
AB  - The Alcohol, Smoking and Substance Involvement Screening Test (ASSIST) is a
      reliable and valid tool to early detection in the harmful and hazardous drug use
      in primary care settings when administered by interview in the general
      population. As the risk of substance related problems in university students is
      high, it is necessary to have screening instruments that can be used beyond the
      health care settings. Thus, we compared a self-report adaptation of ASSIST with
      the validated interview format in a convenience sample of university students. A
      counter-balance design was chosen with students alternating between the interview
      and the self-report formats. Both formats were completed by all students (n=170)
      over 30 days. The scores for total involvement, tobacco, alcohol, cannabis and
      cocaine obtained from the two formats demonstrated good intra-class correlation
      coefficient (ICC >0.60). The agreement assessed by kappa between questions of the
      two formats was considered moderate for tobacco (0.76) and cannabis (0.69) and
      discrete for alcohol (0.47). The consistency of the self-report questionnaire was
      also good to moderate (Cronbach's alpha of 0.90 for tobacco, 0.71 for alcohol,
      0.86 for cannabis and 0.89 for cocaine) and showed acceptable sensitivity (66.7
      100%) and specificity (83.5-97.1%) for tobacco, alcohol, cannabis and cocaine
      when compared to the ASSIST interview format (gold standard). The findings
      suggest that self-report version is as acceptable as the interview and that the
      scores on the two formats are comparable. However, the participants reported more
      motivation for change behavior and more concern about substance use when they
      were interviewed.

PMID- 24727112
TI  - The role of personality variables in drinking game participation.
AB  - Drinking games are prevalent among college student and associated with increased
      risk of experiencing negative alcohol-related consequences. Personality
      variables, and specifically impulsivity and sensation seeking, have been linked
      to increased alcohol consumption and related negative consequences, but research
      on the relationship between personality and drinking game participation is
      limited. The current study used path analysis to assess the impact of sensation
      seeking and impulsivity on frequency of drinking game participation and related
      consequences in a sample of undergraduate college students. Findings suggest that
      sensation seeking and impulsivity are positively associated with frequency of
      drinking game participation. Both impulsivity and sensation seeking had a direct
      effect on negative consequences associated with drinking games, and both had an
      indirect relationship when controlling for the frequency of drinking game
      participation. The results are largely consistent with previous studies in
      suggesting that impulsivity and sensation seeking play a role in predicting risky
      alcohol use and related negative consequences. Understanding the relationship
      between personality variables and negative drinking game consequences may better
      inform the treatment of hazardous drinking among college students.

PMID- 24727113
TI  - Do ethnicity and gender moderate the influence of posttraumatic stress disorder
      on time to smoking lapse?
AB  - BACKGROUND: Following a smoking cessation attempt, smokers with posttraumatic
      stress disorder (PTSD) experience smoking relapse at a higher and faster rate.
      Black ethnicity and female gender are also associated with lower success rates
      following smoking cessation. No study to date has prospectively examined how
      ethnicity and gender may moderate the effect of PTSD on smoking relapse. It was
      hypothesized that female gender and Black ethnicity would significantly predict
      early lapse after quitting; further, it was predicted that ethnicity and gender
      would moderate the effect of PTSD on relapse rate. METHODS: Smokers with PTSD
      (n=48) and without PTSD (n=56) completed ecological momentary assessment (EMA)
      the week after a quit date, and self-initiated EMA entries after smoking lapse.
      Smoking abstinence was biologically verified. The sample included Black (62%) and
      White (38%) participants, and was 50% female. Study hypotheses were tested with
      Cox proportional hazards regression modeling time to first smoking lapse.
      RESULTS: Study results confirmed the main hypothesis, with a significant PTSD *
      Ethnicity interaction emerging. The effect of PTSD on smoking relapse was
      significant for White participants but not for Black participants. No significant
      gender moderation was found. CONCLUSION: Taken together, study results support
      previous research, and suggest that the relationship between smoking and PTSD is
      stronger for White smokers than for minorities. This study has significant
      implications for research in smoking and mental disease, as well as for smoking
      cessation treatments for Black smokers.

PMID- 24727115
TI  - Pathological gambling subtypes: A comparison of treatment-seeking and non
      treatment-seeking samples from Brazil and Canada.
AB  - BACKGROUND: Pathological gambling (PG) is a heterogeneous disorder. The
      identification and characterization of PG subtypes could lead to tailored
      treatment approaches, which may, in turn, improve treatment outcomes. OBJECTIVE:
      To investigate PG subtypes based on personality traits across two different
      cultural and clinical settings. Consistent with the Pathways Model, we
      hypothesized the presence of three subtypes (behaviorally conditioned - BC,
      emotionally vulnerable - EV, and antisocial impulsivist - AI). METHODS: 140 PG
      adults from Sao Paulo, Brazil (SP sample) and 352 adults with PG (n=214) or sub
      clinical PG (n=138) from Toronto, Canada (TO sample) completed the Temperament
      and Character Inventory (TCI). Latent-class analysis was used to investigate
      subtypes. RESULTS: A 2-class solution was the best model for the pooled SP and TO
      samples. Class 1 presented a normative personality profile and was composed
      exclusively of participants from Toronto (BC subtype). Class 2 was characterized
      by high novelty seeking, high harm avoidance, and low self-directedness, and
      included participants from both SP and TO (EV subtype). When sub-clinical PGs
      were excluded from the analysis, a single-class solution better characterized the
      SP and TO samples. CONCLUSIONS: Our results suggest that PG severity, rather than
      community or clinical settings, may have an effect on PG subtypes. The
      generalizability of the results is limited by the demographic and clinical
      features of the selected samples. Future neurobiological studies may contribute
      to the categorization of subjects into PG subtypes based on different underlying
      biological pathways.

PMID- 24727114
TI  - Children's exposure to parental conflict after father's treatment for alcoholism.
AB  - OBJECTIVE: This study investigated children of alcoholics' (COAs) exposure to
      inter-parental conflict before and after their fathers received alcohol treatment
      and compared exposure levels to a community comparison sample. METHOD: This study
      included 67 couples with a treatment-seeking male alcoholic partner and children
      aged 4-16. The alcoholic fathers and their relationship partners provided data at
      baseline and at six and twelve month follow-ups. A community comparison sample of
      78 couples with children in the target age range completed similar longitudinal
      assessments. It was hypothesized that treatment of paternal alcoholism would be
      associated with a decrease in COAs' exposure to conflict, and that among remitted
      patients exposure to conflict would decrease to the level found in the community
      sample. RESULTS: Prior to the father's alcohol treatment, the children of the
      treatment sample were exposed to significantly more conflict between their
      parents than in the community comparison sample. After the fathers received
      alcohol treatment, COAs' exposure to conflict significantly decreased at both the
      six and twelve month follow-ups compared to baseline. Children of remitted
      alcoholics did not differ significantly in levels of exposure to conflict at six
      months follow-up compared to the community sample as predicted. However, at
      twelve months remitted alcoholics reported significantly more exposure to
      conflict compared to the community sample. CONCLUSIONS: Decreased child exposure
      to parental conflict is a benefit associated with the father's treatment for
      alcoholism, and it may lead to improvements in COAs' functioning after parental
      treatment.

PMID- 24727116
TI  - Formation of carbonated hydroxyapatite films on metallic surfaces using
      dihexadecyl phosphate-LB film as template.
AB  - Hydroxyapatite serves as a bioactive material for biomedical purposes, because it
      shares similarities with the inorganic part of the bone. However, how this
      material deposits on metallic surfaces using biomimetic matrices remains unclear.
      In this study, we deposited dihexadecyl phosphate, a phospholipid that bears a
      simple chemical structure, on stainless steel and titanium surfaces using the
      Langmuir-Blodgett (LB) technique; we employed the resulting matrix to grow
      carbonated hydroxyapatite. We obtained the calcium phosphate coating via a two
      step process: we immersed the surfaces modified with the LB films into phosphate
      buffer, and then, we exposed the metal to a solution that simulated the
      concentration of ions in the human plasma. The latter step generated carbonated
      hydroxyapatite, the same mineral existing in the bone. The free energy related to
      the surface roughness and composition increased after we modified the supports.
      We investigated the film morphology by scanning electron and atomic force
      microscopies and determined surface composition by infrared spectroscopy and
      energy dispersive X-ray. We also studied the role of the surface roughness and
      the surface chemistry on cell viability. The surface-modified Ti significantly
      increased osteoblastic cells proliferation, supporting the potential use of these
      surfaces as osteogenic materials. 

PMID- 24727117
TI  - Electrophoretic deposition of cellulose nanocrystals (CNs) and CNs/alginate
      nanocomposite coatings and free standing membranes.
AB  - This study presents the electrophoretic deposition (EPD) of cellulose
      nanocrystals (CNs) and CNs-based alginate composite coatings for biomedical
      applications. The mechanism of anodic deposition of CNs and co-deposition of
      CNs/alginate composites was analyzed based on the results of zeta-potential,
      Fourier transform infrared spectroscopy and scanning electron microscopy (SEM)
      analyses. The capability of the EPD technique for manipulating the orientation of
      CNs and for the preparation of multilayer CNs coatings was demonstrated. The
      nanotopographic surface roughness and hydrophilicity of the deposited coatings
      were measured and discussed. Electrochemical testing demonstrated that a
      significant degree of corrosion protection of stainless steel could be achieved
      when CNs-containing coatings were present. Additionally, the one-step EPD-based
      processing of free-standing CNs/alginate membranes was demonstrated confirming
      the versatility of EPD to fabricate free-standing membrane structures compared to
      a layer-by-layer deposition technique. CNs and CNs/alginate nanocomposite
      coatings produced by EPD are potential candidates for biomedical, cell technology
      and drug delivery applications. 

PMID- 24727118
TI  - alphas-Casein-PE6400 mixtures: surface properties, miscibility and self-assembly.
AB  - Surface properties, miscibility and self-assembly of mixtures of a food-grade
      alphas-casein and the triblock copolymer PE6400 (PEO13-PPO30-PEO13) were
      examined. The properties at the surface were determined by surface pressure
      measurements for a 1:1 molar mixture. Comparison of the measured with the
      calculated isotherms show attractive interactions at surface pressures above
      9mN/m. The miscibility gaps of solutions containing 0.004-0.2mmol/l alphas-casein
      and 0.02-0.1mol/l polymer were examined. It was found that a one-phase region
      exists at distinct mixing ratios and temperatures. Comparison of the cloud points
      of mixtures of alphas-casein and PE6400 with pure alphas-casein showed that the
      presence of the triblock copolymer enhanced the solubility of the protein. The
      zeta-potential of the alphas-casein solution decreased by addition of PE6400 to
      zero. Our results thus suggest that alphas-casein and PE6400 are miscible. The
      results of the cloud point and zeta-potential measurements were explained by
      formation of a mixed aggregate where the PPO chains are anchored inside the
      hydrophobic part of the alphas-casein while the PEO chains cover the charged
      hydrophilic part of the alphas-casein thereby leading to an increase of the cloud
      point and a decrease in zeta-potential. This is in agreement with the attractive
      interactions between alphas-casein and PE6400 as observed via surface pressure
      measurements at the surface. 

PMID- 24727119
TI  - Effects of the application sequence of calcium-containing desensitising pastes
      during etch-and-rinse adhesive restoration.
AB  - OBJECTIVES: To evaluate the effects of different application sequence of calcium
      containing desensitising pastes on bonding effectiveness and tubule occlusion
      during etch-and-rinse (E&R) adhesive restoration. METHODS: Seventy molars were
      sectioned parallel to the occlusal plane, polished and randomly divided into
      seven groups (n=10). Group 1 was etched with 35% phosphoric acid for 15s. Groups
      2-4 were treated with different calcium-containing desensitisers, including an
      arginine-calcium carbonate (Arg-CaCO3)-containing paste, a casein phosphopeptide
      amorphous calcium phosphate (CPP-ACP)-containing paste and a calcium-sodium
      phosphosilicate (Novamin)-containing paste, respectively. Afterward, these groups
      were etched with 35% phosphoric acid for 15s. Groups 5-7 were initially etched
      and then treated with Arg-CaCO3-, CPP-ACP- and Novamin-containing desensitisers,
      respectively. In each group, samples were equally distributed into two subgroups
      (n=5) to bond with either a two-step E&R adhesive Adper SingleBond 2 (SB) or a
      three-step E&R adhesive Adper ScotchBond Multi-Purpose (SBMP). The microtensile
      bond strengths (MTBS) were tested and fracture modes were analyzed by
      stereomicroscopy and field-emission scanning electron microscopy (FESEM). Eight
      additional dentine disks were prepared to evaluate tubule occlusion prior to
      bonding using FESEM. RESULTS: The application sequence of calcium-containing
      desensitising pastes did not significantly affect MTBS irrespective of two-step
      SB (P>0.05) or three-step SBMP E&R adhesives (P>0.05). Effective dentinal tubule
      occlusion was observed in the mode of etching-desensitising. CONCLUSIONS:
      Applying calcium-containing desensitisers (particularly Arg-CaCO3- and Novamin
      based) after etching during E&R adhesive restoration could achieve effective
      tubule occlusion without affecting the bonding strength.

PMID- 24727121
TI  - When specific gut microbes reveal a possible link between hepatic steatosis and
      adipose tissue.

PMID- 24727122
TI  - TACE vs. surgical resection for BCLC stage B HCC.

PMID- 24727120
TI  - Hc-daf-2 encodes an insulin-like receptor kinase in the barber's pole worm,
      Haemonchus contortus, and restores partial dauer regulation.
AB  - Infective L3s (iL3s) of parasitic nematodes share common behavioural,
      morphological and developmental characteristics with the developmentally arrested
      (dauer) larvae of the free-living nematode Caenorhabditis elegans. It is proposed
      that similar molecular mechanisms regulate entry into or exit from the dauer
      stage in C. elegans, and the transition from free-living to parasitic forms of
      parasitic nematodes. In C. elegans, one of the key factors regulating the dauer
      transition is the insulin-like receptor (designated Ce-DAF-2) encoded by the gene
      Ce-daf-2. However, nothing is known about DAF-2 homologues in most parasitic
      nematodes. Here, using a PCR-based approach, we identified and characterised a
      gene (Hc-daf-2) and its inferred product (Hc-DAF-2) in Haemonchus contortus (a
      socioeconomically important parasitic nematode of ruminants). The sequence of Hc
      DAF-2 displays significant sequence homology to insulin receptors (IR) in both
      vertebrates and invertebrates, and contains conserved structural domains. A
      sequence encoding an important proteolytic motif (RKRR) identified in the
      predicted peptide sequence of Hc-DAF-2 is consistent with that of the human IR,
      suggesting that it is involved in the formation of the IR complex. The Hc-daf-2
      gene was transcribed in all life stages of H. contortus, with a significant up
      regulation in the iL3 compared with other stages. To compare patterns of
      expression between Hc-daf-2 and Ce-daf-2, reporter constructs fusing the Ce-daf-2
      or Hc-daf-2 promoter to sequence encoding GFP were microinjected into the N2
      strain of C. elegans, and transgenic lines were established and examined. Both
      genes showed similar patterns of expression in amphidial (head) neurons, which
      relate to sensation and signal transduction. Further study by heterologous
      genetic complementation in a daf-2-deficient strain of C. elegans (CB1370) showed
      partial rescue of function by Hc-daf-2. Taken together, these findings provide a
      first insight into the roles of Hc-daf-2/Hc-DAF-2 in the biology and development
      of H. contortus, particularly in the transition to parasitism. 

PMID- 24727123
TI  - Simeprevir with peginterferon/ribavirin for treatment-naive hepatitis C genotype
      1 patients in Japan: CONCERTO-1, a phase III trial.
AB  - BACKGROUND & AIMS: In a Japanese Phase II study, the hepatitis C virus NS3/4A
      protease inhibitor simeprevir demonstrated potent antiviral activity and
      significantly improved sustained virologic response rates when added to
      peginterferon alpha-2a/ribavirin in treatment-naive patients infected with
      hepatitis C virus genotype 1. METHODS: CONCERTO-1 was a Phase III, randomized,
      double-blind, placebo-controlled trial. Treatment-naive adults (? 70 years) with
      chronic hepatitis C virus genotype 1 infection (hepatitis C virus RNA ? 5 log10
      IU/ml) were randomized (2:1) to simeprevir 100mg once-daily with peginterferon
      alpha-2a/ribavirin for 12 weeks then response-guided therapy with peginterferon
      alpha-2a/ribavirin for 12 or 36 weeks, or to placebo with peginterferon alpha
      2a/ribavirin for 12 weeks then peginterferon alpha-2a/ribavirin for 36 weeks.
      RESULTS: Overall, 183 patients were treated. Sustained virologic response 12
      weeks after treatment end (primary efficacy endpoint) was achieved in 88.6% of
      simeprevir- and 61.7% of placebo-treated patients (p<0.0001 for stratum-adjusted
      between-group difference). Overall, 91.9% of simeprevir-treated patients met
      response-guided therapy criteria and completed treatment at week 24; sustained
      virologic response rate at 12 weeks in these patients was 92.0%. One simeprevir-
      (0.8%) and two placebo-treated patients (3.3%) experienced viral breakthrough;
      respective viral relapse rates were 7.6% and 30.6%. Overall adverse event profile
      in simeprevir-treated patients was comparable to that in patients who received
      peginterferon alpha-2a/ribavirin alone. CONCLUSIONS: Simeprevir once daily with
      peginterferon alpha-2a/ribavirin significantly improved sustained virologic
      response rate 12 weeks after treatment end in treatment-naive patients with
      chronic hepatitis C virus genotype 1 infection, with a shorter 24-week treatment
      duration in most patients.

PMID- 24727125
TI  - The crystal structure of the anti-sigma factor CnrY in complex with the sigma
      factor CnrH shows a new structural class of anti-sigma factors targeting
      extracytoplasmic function sigma factors.
AB  - Gene expression in bacteria is regulated at the level of transcription
      initiation, a process driven by sigma factors. The regulation of sigma factor
      activity proceeds from the regulation of their cytoplasmic availability, which
      relies on specific inhibitory proteins called anti-sigma factors. With anti-sigma
      factors regulating their availability according to diverse cues, extracytoplasmic
      function sigma factors (sigma(ECF)) form a major signal transduction system in
      bacteria. Here, structure:function relationships have been characterized in an
      emerging class of minimal-size transmembrane anti-sigma factors, using CnrY from
      Cupriavidus metallidurans CH34 as a model. This study reports the 1.75-A
      resolution structure of CnrY cytosolic domain in complex with CnrH, its cognate
      sigma(ECF), and identifies a small hydrophobic knob in CnrY as the major
      determinant of this interaction in vivo. Unsuspected structural similarity with
      the molecular switch regulating the general stress response in alpha
      proteobacteria unravels a new class of anti-sigma factors targeting sigma(ECF).
      Members of this class carry out their function via a 30-residue stretch that
      displays helical propensity but no canonical structure on its own. 

PMID- 24727124
TI  - Towards predictive models of the human gut microbiome.
AB  - The intestinal microbiota is an ecosystem susceptible to external perturbations
      such as dietary changes and antibiotic therapies. Mathematical models of
      microbial communities could be of great value in the rational design of
      microbiota-tailoring diets and therapies. Here, we discuss how advances in
      another field, engineering of microbial communities for wastewater treatment
      bioreactors, could inspire development of mechanistic mathematical models of the
      gut microbiota. We review the state of the art in bioreactor modeling and current
      efforts in modeling the intestinal microbiota. Mathematical modeling could
      benefit greatly from the deluge of data emerging from metagenomic studies, but
      data-driven approaches such as network inference that aim to predict microbiome
      dynamics without explicit mechanistic knowledge seem better suited to model these
      data. Finally, we discuss how the integration of microbiome shotgun sequencing
      and metabolic modeling approaches such as flux balance analysis may fulfill the
      promise of a mechanistic model. 

PMID- 24727126
TI  - Identification of active VQ motif-containing genes and the expression patterns
      under low nitrogen treatment in soybean.
AB  - Plant VQ motif-containing protein family plays crucial roles in plant growth,
      seed development, and defense responses in Arabidopsis. However, its function in
      soybean is still not well defined. We aim to identify the VQ gene family, and
      explore the genetic variation of active GmVQ genes in soybean and their
      expression patterns under low nitrogen stresses. A total of 74 VQ motif
      containing genes were identified in soybean genome, and were clustered into five
      distinct subfamilies (GmVQI-V) with each gene having two or three copies except
      GmVQ55 (GmVQIV) with single copy. Fourteen genes with relatively high expression
      level, at least in one tissue, were defined as active GmVQ genes. Most of these
      active GmVQ genes specifically expressed in soybean pod shell (7/74), root (9/74)
      and/or nodule (10/74) respectively. Single nucleotide polymorphism (SNP) analysis
      in cultivated and wild soybeans revealed there were selected site(s) in GmVQ6,
      GmVQ7, GmVQ10, GmVQ26 and GmVQ61, which means that these genes have undergone
      artificial selection during soybean domestication. After low nitrogen treatment,
      enhanced expression of VQ genes was noticed in specific tissues, such as GmVQ53,
      GmVQ26, GmVQ58, GmVQ61, GmVQ70 and GmVQ6 in shoot, and GmVQ53, GmVQ58, GmVQ48 in
      root. On the contrary, suppressed expression of GmVQ57, GmVQ21 and GmVQ1 genes
      was noticed in root after the treatment. Duplicated copy of the active GmVQ genes
      showed similar expression pattern, suggesting that these genes might be complete
      copies. The results suggested that soybean VQ-motif containing genes may act as
      positive or negative regulators in soybean growth, development and nitrogen
      metabolism. Taken together, our results provided useful information for
      functional characterization of soybean GmVQ genes to unravel their biological
      roles.

PMID- 24727127
TI  - Nucleoside monophosphorothioates as the new hydrogen sulfide precursors with
      unique properties Pharmacological Research, 81, 2014, Pages 34-43.

PMID- 24727129
TI  - Unprotected carotid artery stenting in symptomatic elderly patients: a single
      center experience.
AB  - BACKGROUND AND PURPOSE: Surgery is known to have fewer adverse events in patients
      aged >75 years with carotid stenosis, but some are not candidates due to
      comorbidity. Stenting using protection devices is the most accepted endovascular
      technique. Our aim is to show the safety and efficacy of carotid stenting without
      any protection device in these patients. MATERIAL AND METHODS: All patients older
      than 75 years with carotid stenosis treated in our center between January 2002
      and December 2012 were included in this prospective study. All were treated by
      carotid stenting without protection devices. Angiographic results, neurologic
      complications and Doppler ultrasound were collected during the procedure and
      within 30 days. RESULTS: 49 patients were included (mean age 78.2 years, range 75
      86). The average degree of stenosis was 88.2%. During the procedure there were
      two cases of transient ischemic attack and one intraparenchymal hemorrhage. At 30
      days there was a non-disabling stroke. The combined rate of disabling stroke plus
      myocardial infarction plus death was 6% at 30 days and the rate of any stroke was
      4% during the procedure and 2% at 30 days. CONCLUSIONS: Endovascular treatment of
      carotid stenosis without protection devices in symptomatic patients aged >75
      years is an alternative to endovascular treatment with protection devices.
      Complications and mortality rates are similar to studies that used protection
      devices in lower risk patients.

PMID- 24727130
TI  - A novel model of large vessel ischemic stroke in rabbits: microcatheter occlusion
      of the posterior cerebral artery.
AB  - BACKGROUND AND PURPOSE: The rabbit small clot embolic model for large vessel
      occlusion (LVO) is well established, yet has limitations. Blind introduction of
      autologous thrombus often fails to completely occlude a target vessel and, when
      successful, the precise timing of occlusion and revascularization is difficult to
      control. Studies of cellular biology and neuroimaging of acute reversible
      cerebral ischemia (ie, penumbral tissue) would benefit from a rabbit model in
      which LVO can be reliably induced, easily confirmed, and in which the time of
      occlusion and revascularization can be precisely controlled. METHODS:
      Transfemoral 1.5 F microcatheterization of the posterior cerebral artery (PCA)
      was performed in anesthetized rabbits (n=7) using fluoroscopic guidance. LVO with
      the wedged microcatheter was maintained for 30-210 min followed by reperfusion.
      Diffusion-weighted and T2 fluid-attenuated inversion recovery (FLAIR) MRI was
      performed 3 h after catheter removal on a 3 T scanner. Post-mortem
      histopathologic analysis of brain tissue was performed using triphenyltetrazolium
      chloride (TTC). RESULTS: Placing of the 1.5 F microcatheter tip in the PCA was
      successful in all seven animals. Infarct size on matched diffusion-weighted and
      TTC sections was strongly correlated (r(2)=0.86). Transient PCA occlusion of 30
      60 min resulted in infarction of the ipsilateral hippocampus and thalamus,
      sparing the cortex, while more prolonged occlusion (180-210 min) resulted in
      cortical infarction as well. CONCLUSIONS: Image-guided microcatheter induction of
      PCA occlusion in rabbits can consistently produce time-dependent infarction of
      cortical and subcortical structures that is reliably detected by diffusion
      weighted MRI, and thus may be a useful model for therapeutic studies in acute
      ischemic stroke.

PMID- 24727128
TI  - Towards understanding methyllysine readout.
AB  - BACKGROUND: Lysine methylation is the most versatile covalent posttranslational
      modification (PTM) found in histones and non-histone proteins. Over the past
      decade a number of methyllysine-specific readers have been discovered and their
      interactions with histone tails have been structurally and biochemically
      characterized. More recently innovative experimental approaches have emerged that
      allow for studying reader interactions in the context of the full nucleosome and
      nucleosomal arrays. SCOPE OF REVIEW: In this review we give a brief overview of
      the known mechanisms of histone lysine methylation readout, summarize progress
      recently made in exploring interactions with methylated nucleosomes, and discuss
      the latest advances in the development of small molecule inhibitors of the
      methyllysine-specific readers. MAJOR CONCLUSIONS: New studies reveal various
      reader-nucleosome contacts outside the methylated histone tail, thus offering a
      better model for association of histone readers to chromatin and broadening our
      understanding of the functional implications of these interactions. In addition,
      some progress has been made in the design of antagonists of these interactions.
      GENERAL SIGNIFICANCE: Specific lysine methylation patterns are commonly
      associated with certain chromatin states and genomic elements, and are linked to
      distinct biological outcomes such as transcription activation or repression.
      Disruption of patterns of histone modifications is associated with a number of
      diseases, and there is tremendous therapeutic potential in targeting histone
      modification pathways. Thus, investigating binding of readers of these
      modifications is not only important for elucidating fundamental mechanisms of
      chromatin regulation, but also necessary for the design of targeted therapeutics.
      This article is part of a Special Issue entitled: Molecular mechanisms of histone
      modification function.

PMID- 24727131
TI  - Extracranial carotid artery stenting followed by intracranial stent-based
      thrombectomy for acute tandem occlusive disease.
AB  - OBJECTIVE: Acute tandem occlusions of the extracranial internal carotid artery
      (ICA) and a major intracranial artery respond poorly to intravenous tissue
      plasminogen activator (tPA) and present an endovascular challenge. We describe
      our experience with emergency stent-assisted ICA angioplasty and intracranial
      stent-based thrombectomy of tandem occlusions. METHODS: Procedures were performed
      from March 2010 to December 2013. National Institutes of Health Stroke Score
      (NIHSS) and Alberta Stroke Program Early CT Score (ASPECTS), occlusion sites,
      collateral supply, procedural details, and outcomes were retrospectively reviewed
      with IRB waiver of informed consent. RESULTS: 24 patients, mean age 66 years,
      mean admission NIHSS 20.4, and mean ASPECTS 9 were included. Occlusion sites were
      proximal ICA-middle cerebral artery (MCA) trunk in 17 patients, proximal ICA-ICA
      terminus in six, and ICA-MCA-anterior cerebral artery in one. Stent-assisted
      cervical ICA recanalization was achieved in all patients, with unprotected pre
      angioplasty in 24/24, unprotected stenting in 16/24 (67%), and protected stenting
      in 8/24 (33%), followed by stent-thrombectomy in 25 intracranial occlusions.
      There was complete recanalization/complete perfusion in 19/24 (79%), complete
      recanalization/partial perfusion in 3/24 (13%), and partial
      recanalization/partial perfusion in 2/24 (8%) with no procedural
      morbidity/mortality. Mean time to therapy was 3.8 h (range 2-5.5) and mean time
      to recanalization was 51 min (range 38-69). At 3-month follow-up, among 17/22
      surviving patients (77%), 13/17 (76%) were modified Rankin Scale (mRS) 0-2 and
      3/17 (18%) were mRS 3. CONCLUSIONS: In acute tandem ICA-MCA/distal ICA
      occlusions, extracranial stenting followed by intracranial stent-based
      thrombectomy appears feasible, effective, and safe. Further evaluation of this
      treatment strategy is warranted.

PMID- 24727132
TI  - Identification of the chemical form of sulfur compounds in the Japanese pink
      coral (Corallium elatius) skeleton using MU-XRF/XAS speciation mapping.
AB  - The distributions and chemical forms of sulfur compounds in the skeleton of
      Japanese pink coral (Corallium elatius) were investigated using X-ray
      spectroscopic techniques combined with micro-focused soft X-ray radiation.
      Microscopic X-ray fluorescence/soft X-ray photoabsorption (MU-XRF/XAS) speciation
      mapping clarified that sulfate is the primary species in the coral skeleton, with
      minor amounts of organic sulfur, whereas both sulfate and organic sulfur coexist
      in coenenchyme. Analysis of the post-edge region of the XAS spectra confirmed
      that sulfate ions in the coral skeleton are mainly in the form of gypsum-like
      inorganic sulfate substituting for the carbonate ions in the calcite skeleton.
      The sulfate concentration was negatively correlated with the magnesium
      concentration and positively correlated with that of phosphorus. Speciation
      mapping of sulfate in the coral skeleton showed clear fluctuations with sulfate
      concentrations being higher at dark bands, whereas the small amount of organic
      sulfur had unclear dark/bright bands. These results suggest that the little
      organic sulfur that is present is contained in the organic matter embedded in the
      biocrystal of coral skeleton. 

PMID- 24727134
TI  - Are APLS formulae for estimating weight appropriate for use in children admitted
      to PICU?
AB  - AIM: To determine if the revised APLS UK formulae for estimating weight are
      appropriate for use in the paediatric intensive care population in the United
      Kingdom. METHODS: A retrospective observational study involving 10,081 children
      (5622 male, 4459 female) between the age of term corrected and 15 years, who were
      admitted to Paediatric Intensive Care Units in the United Kingdom over a five
      year period between 2006 and 2010. Mean weight was calculated using retrospective
      data supplied by the 'Paediatric Intensive Care Audit Network' and this was
      compared to the estimated weight generated using age appropriate APLS UK
      formulae. RESULTS: The formula 'Weight=(0.5*age in months)+4' significantly
      overestimates the mean weight of children under 1 year admitted to PICU by
      between 10% and 25.4%. While the formula 'Weight=(2*age in years)+8' provides an
      accurate estimate for 1-year-olds, it significantly underestimates the mean
      weight of 2-5 year olds by between 2.8% and 4.9%. The formula 'Weight=(3*age in
      years)+7' significantly overestimates the mean weight of 6-11 year olds by
      between 8.6% and 20.7%. Simple linear regression was used to produce novel
      formulae for the prediction of the mean weight specifically for the PICU
      population. CONCLUSIONS: The APLS UK formulae are not appropriate for estimating
      the weight of children admitted to PICU in the United Kingdom. Relying on mean
      weight alone will result in significant error as the standard deviation for all
      age groups are wide.

PMID- 24727133
TI  - A method for 3D-reconstruction of a muscle thick filament using the tilt series
      images of a single filament electron tomogram.
AB  - Myosin interacting-heads (MIH) motifs are visualized in 3D-reconstructions of
      thick filaments from striated muscle. These reconstructions are calculated by
      averaging methods using images from electron micrographs of grids prepared using
      numerous filament preparations. Here we propose an alternative method to
      calculate the 3D-reconstruction of a single thick filament using only a tilt
      series images recorded by electron tomography. Relaxed thick filaments, prepared
      from tarantula leg muscle homogenates, were negatively stained. Single-axis tilt
      series of single isolated thick filaments were obtained with the electron
      microscope at a low electron dose, and recorded on a CCD camera by electron
      tomography. An IHRSR 3D-recontruction was calculated from the tilt series images
      of a single thick filament. The reconstruction was enhanced by including in the
      search stage dual tilt image segments while only single tilt along the filament
      axis is usually used, as well as applying a band pass filter just before the back
      projection. The reconstruction from a single filament has a 40 A resolution and
      clearly shows the presence of MIH motifs. In contrast, the electron tomogram 3D
      reconstruction of the same thick filament - calculated without any image
      averaging and/or imposition of helical symmetry - only reveals MIH motifs
      infrequently. This is - to our knowledge - the first application of the IHRSR
      method to calculate a 3D reconstruction from tilt series images. This single
      filament IHRSR reconstruction method (SF-IHRSR) should provide a new tool to
      assess structural differences between well-ordered thick (or thin) filaments in a
      grid by recording separately their electron tomograms.

PMID- 24727135
TI  - Reply to letter: Requirement for a structured algorithm in cardiac arrest
      following major trauma: epidemiology, management errors, and preventability of
      traumatic deaths in Berlin.

PMID- 24727137
TI  - Predictors of long-term survival after out-of-hospital cardiac arrest: the impact
      of Activities of Daily Living and Cerebral Performance Category scores.
AB  - BACKGROUND: Current focus on immediate survival from out-of-hospital cardiac
      arrest (OHCA) has diverted attention away from the variables potentially
      affecting long-term survival. AIM: To determine the relationship between
      neurological and functional status at hospital discharge and long-term survival
      after OHCA. METHODS: Prospective data collection for all OHCA patients aged >18
      years in the Jerusalem district (n=1043, 2008-2009). PRIMARY OUTCOME MEASURE:
      Length of survival after OHCA. Potential predictors: Activities of Daily Living
      (ADL) and Cerebral Performance Category (CPC) scores at hospital discharge, age
      and sex. RESULTS: There were 52/279 (18.6%) survivors to hospital discharge.
      Fourteen were discharged on mechanical ventilation (27%). Interviews with
      survivors and/or their legal guardians were sought 2.8+/-0.6 years post-arrest.
      Eighteen died before long-term follow-up (median survival 126 days, IQR 94-740).
      Six improved their ADL and CPC scores between discharge and follow-up. Long-term
      survival was positively related with lower CPC scores (p=0.002) and less
      deterioration in ADL from before the arrest to hospital discharge (p=0.001). For
      each point increment in ADL at hospital discharge, the hazard ratio of death was
      1.31 (95%CI 1.12, 1.53, p=0.001); this remained unchanged after adjustment for
      age and sex (HR 1.26, 95%CI 0.07, 1.48, p=0.005). CONCLUSIONS: One-third of the
      patients discharged from hospital after OHCA died within 30 months of the event.
      Long-term survival was associated both with better neurological and functional
      level at hospital discharge and a smaller decrease in functional limitation from
      before to after the arrest, yet some patients with a poor neurological outcome
      survived prolonged periods after hospital discharge.

PMID- 24727136
TI  - Global and regional differences in cerebral blood flow after asphyxial versus
      ventricular fibrillation cardiac arrest in rats using ASL-MRI.
AB  - Both ventricular fibrillation cardiac arrest (VFCA) and asphyxial cardiac arrest
      (ACA) are frequent causes of CA. However, only isolated reports compared cerebral
      blood flow (CBF) reperfusion patterns after different types of CA, and even fewer
      reports used methods that allow serial and regional assessment of CBF. We
      hypothesized that the reperfusion patterns of CBF will differ between individual
      types of experimental CA. In a prospective block-randomized study, fentanyl
      anesthetized adult rats were subjected to 8min VFCA or ACA. Rats were then
      resuscitated with epinephrine, bicarbonate, manual chest compressions and
      mechanical ventilation. After the return of spontaneous circulation, CBF was then
      serially assessed via arterial spin-labeling magnetic resonance imaging (ASL-MRI)
      in cortex, thalamus, hippocampus and amygdala/piriform complex over 1h
      resuscitation time (RT). Both ACA and VFCA produced significant temporal and
      regional differences in CBF. All regions in both models showed significant
      changes over time (p<0.01), with early hyperperfusion and delayed hypoperfusion.
      ACA resulted in early hyperperfusion in cortex and thalamus (both p<0.05 vs.
      amygdala/piriform complex). In contrast, VFCA induced early hyperperfusion only
      in cortex (p<0.05 vs. other regions). Hyperperfusion was prolonged after ACA,
      peaking at 7min RT (RT7; 199% vs. BL, Baseline, in cortex and 201% in thalamus,
      p<0.05), then returning close to BL at ~RT15. In contrast, VFCA model induced
      mild hyperemia, peaking at RT7 (141% vs. BL in cortex). Both ACA and VFCA showed
      delayed hypoperfusion (ACA, ~30% below BL in hippocampus and amygdala/piriform
      complex, p<0.05; VFCA, 34-41% below BL in hippocampus and amygdala/piriform
      complex, p<0.05). In conclusion, both ACA and VFCA in adult rats produced
      significant regional and temporal differences in CBF. In ACA, hyperperfusion was
      most pronounced in cortex and thalamus. In VFCA, the changes were more modest,
      with hyperperfusion seen only in cortex. Both insults resulted in delayed
      hypoperfusion in all regions. Both early hyperperfusion and delayed hypoperfusion
      may be important therapeutic targets. This study was approved by the University
      of Pittsburgh IACUC 1008816-1. 

PMID- 24727138
TI  - The association between personal sun exposure, serum vitamin D and global
      methylation in human lymphocytes in a population of healthy adults in South
      Australia.
AB  - BACKGROUND: There is a positive association between solar UV exposure and
      micronucleus frequency in peripheral blood lymphocytes (PBL) and this association
      may be stronger when serum vitamin D (25(OH)D) levels are insufficient (<50
      nmol/L). Micronucleus formation can result from global hypomethylation of DNA
      repeat sequences. The aim of this analysis was to evaluate the relationship
      between solar UV exposure and methylation pattern in LINE-1 repetitive elements
      in PBL DNA and to see if serum 25(OH)D levels modify it. METHOD: Personal solar
      UV exposure was estimated from hours of outdoor exposure over 6 weeks recalled at
      the time of blood collection in 208 male and female participants living in South
      Australia. Methylation in LINE-1 repetitive elements was assessed in PBL using
      pyrosequencing. RESULTS: Methylation in LINE-1 decreased with increasing solar UV
      exposure (% decrease = 0.5% per doubling of sUV; 95%CI: -0.7 to -0.2 p(value) =
      0.00003). Although there was no correlation between LINE-1 methylation and
      micronucleus frequency, there was a 4.3% increase (95%CI: 0.6-8.1 p-value = 0.02)
      in nucleoplasmic bridges and a 4.3% increase in necrosis (CI: 1.9-6.8 p-value =
      0.0005) for every 1% increase in LINE-1 methylation. Serum 25(OH)D was not
      associated with DNA methylation; or did it modify the association of solar UV
      with DNA methylation. CONCLUSION: Exposure to solar UV radiation may reduce DNA
      methylation in circulating lymphocytes. This association does not appear to be
      influenced or mediated by vitamin D status.

PMID- 24727139
TI  - Unique molecular alteration patterns in von Hippel-Lindau (VHL) gene in a cohort
      of sporadic renal cell carcinoma patients from Pakistan.
AB  - BACKGROUND: Renal cell carcinoma (RCC) is the most frequent form of kidney cancer
      in adults. Somatic mutations that inactivate the von Hippel-Lindau (VHL) gene are
      the most common cause of RCC. The frequencies of molecular changes in the VHL
      gene in RCCs vary among different populations. So far, a single chromosomal-based
      study has been reported from a South Asian population. This report presents, for
      the first time, the somatic changes and promoter hypermethylation in VHL in a
      cohort of 300 RCC patients from Pakistan. METHODS: To identify mutations in the
      VHL gene, direct DNA sequencing was carried out. Epigenetic silencing was
      investigated by using methylation-specific polymerase chain reaction. RESULTS:
      Our data showed molecular alterations in the VHL gene in 163 (54%) renal cell
      carcinoma patients. Somatic mutations were found in 87 (29%) patients and 35
      novel mutations were identified. VHL promoter hyper-methylation analysis showed
      epigenetic changes in 106 (35%) out of 300 patients. Patients who had no evidence
      of molecular alterations in the VHL gene were significantly younger than patients
      who carried some molecular change. Molecular alterations in the VHL gene were not
      restricted to clear-cell RCCs (ccRCCs). CONCLUSIONS: This is the first report
      that identifies molecular aberrations in the VHL gene from a South Asian
      population. The frequency of somatic mutation is lower and that of promoter
      hypermethylation is higher when compared with data from other parts of the world.
      The data has important implications in the population-specific application of
      tailored preventive and therapeutic regimens in non-familial RCCs.

PMID- 24727140
TI  - Stability and activity of hydroxyethyl starch-coated polyplexes in frozen
      solutions or lyophilizates.
AB  - Despite their great potential, gene delivery polyplexes have a number of
      limitations, including their tendency for aggregation in vivo or upon storage. In
      previous studies, we could show that hydroxyethyl starch (HES)-decoration of
      polyplexes reduces aggregation in vitro and in vivo. The current study
      investigates the ability of HES-decoration to improve the stability of polyplexes
      upon storage as frozen-liquid or lyophilizate, and uses naked polyplexes or
      PEGylated ones as controls. For this purpose, freeze-thaw (FT) experiments of the
      polyplexes were conducted in the presence of standard excipients (glucose,
      sucrose or trehalose). Dynamic light scattering (DLS) measurements showed that
      HES-decoration imparted better stability when glucose was used, while both HES
      and PEG were effective in inhibiting aggregation in the presence of trehalose or
      sucrose. In contrast, the lyophilized HES-coated polyplexes were more stable than
      the PEGylated ones as shown by DLS, even after storage for 10 weeks at an
      elevated temperature. Evaluation of the gene transfer efficiency of the stored
      samples showed no negative effect of storage, except for the lyophilized naked
      polyplexes. In general, this study shows that, while both HES- or PEG-coats could
      prevent aggregation under frozen-liquid storage, the HES-coat resulted in
      superior protective effect upon lyophilization, with possible advantages for in
      vivo application. In summary, our developed HES-coats provided effective cryo-
      and lyoprotection to the DNA polyplexes. 

PMID- 24727141
TI  - Accelerating the dissolution of enteric coatings in the upper small intestine:
      evolution of a novel pH 5.6 bicarbonate buffer system to assess drug release.
AB  - Despite rapid dissolution in compendial phosphate buffers, gastro resistant
      (enteric coated) products can take up to 2 h to disintegrate in the human small
      intestine, which clearly highlights the inadequacy of the in vitro test method to
      predict in vivo behaviour of these formulations. The aim of this study was to
      establish the utility of a novel pH 5.6 bicarbonate buffer, stabilized by an Auto
      pHTM System, as a better surrogate of the conditions of the proximal small
      intestine to investigate the dissolution behaviour of standard and accelerated
      release enteric double coating formulations. Prednisolone tablets were coated
      with 3 or 5 mg/cm(2) of partially neutralized EUDRAGIT((r)) L 30 D-55, HP-55 or
      HPMC adjusted to pH 6 or 8. An outer layer of EUDRAGIT((r)) L 30 D-55 was applied
      at 5mg/cm(2). For comparison purposes, a standard single layer of EUDRAGIT((r)) L
      30 D-55 was applied to the tablets. Dissolution was carried out using USP II
      apparatus in 0.1 M HCl for 2 h, followed by pH 5.6 bicarbonate buffer.
      EUDRAGIT((r)) L 30 D-55 single-coated tablets showed a slow drug release with a
      lag time of 75 min in buffer, whereas release from the EUDRAGIT((r)) L 30 D-55
      double-coated tablets was accelerated. These in vitro lag times closely match the
      in vivo disintegration times for these coated tablets reported previously. Drug
      release was further accelerated from modified double coatings, particularly in
      the case of coatings with a thinner inner layer of HP-55 or HPMC (pH 8 and
      KH2PO4). This study confirms that the pH 5.6 bicarbonate buffer system offers
      significant advantages during the development of dosage forms designed to release
      the drug in the upper small intestine.

PMID- 24727142
TI  - A comparative ex vivo drug permeation study of beta-blockers through porcine
      buccal mucosa.
AB  - Apparent permeability coefficients (kp) of a series of beta-blockers: acebutolol,
      atenolol, labetalol, metoprolol, oxprenolol and propranolol, through porcine
      buccal mucosa were determined. The aim of the study was to determine the
      permeation parameters (apparent permeability coefficient, kp; flux, J; and lag
      time, TL) as a measure of the intrinsic permeability of porcine buccal mucosa to
      these drugs, in order to predict the efficacy of their possible administration
      through human buccal mucosa. A positive linear correlation was observed between
      the apparent permeability coefficient, kpand the partition coefficient, P.
      Oxprenolol and propranolol are the drugs that presented the highest values of kp:
      0.3231*10(2) cm/h and 0.5666*10(2) cm/h, respectively. Multiple linear regression
      (MLR) using least square estimation was performed on the data set with logkpas
      dependent variable and the descriptors as predictor variables. The potential
      systemic capacity after a buccal administration was predicted by estimating the
      plasma concentrations at steady-stated (Css). Considering the entire process of
      permeation ex vivo, propranolol and oxprenolol would seem to be the best
      candidates for administration through the buccal mucosa.

PMID- 24727143
TI  - Setting objective thresholds for rare event detection in flow cytometry.
AB  - The accurate identification of rare antigen-specific cytokine positive cells from
      peripheral blood mononuclear cells (PBMC) after antigenic stimulation in an
      intracellular staining (ICS) flow cytometry assay is challenging, as cytokine
      positive events may be fairly diffusely distributed and lack an obvious
      separation from the negative population. Traditionally, the approach by flow
      operators has been to manually set a positivity threshold to partition events
      into cytokine-positive and cytokine-negative. This approach suffers from
      subjectivity and inconsistency across different flow operators. The use of
      statistical clustering methods does not remove the need to find an objective
      threshold between between positive and negative events since consistent
      identification of rare event subsets is highly challenging for automated
      algorithms, especially when there is distributional overlap between the positive
      and negative events ("smear"). We present a new approach, based on the Fbeta
      measure, that is similar to manual thresholding in providing a hard cutoff, but
      has the advantage of being determined objectively. The performance of this
      algorithm is compared with results obtained by expert visual gating. Several ICS
      data sets from the External Quality Assurance Program Oversight Laboratory
      (EQAPOL) proficiency program were used to make the comparisons. We first show
      that visually determined thresholds are difficult to reproduce and pose a problem
      when comparing results across operators or laboratories, as well as problems that
      occur with the use of commonly employed clustering algorithms. In contrast, a
      single parameterization for the Fbeta method performs consistently across
      different centers, samples, and instruments because it optimizes the
      precision/recall tradeoff by using both negative and positive controls. 

PMID- 24727144
TI  - Validated detection of human anti-chimeric immune responses in serum of
      neuroblastoma patients treated with ch14.18/CHO.
AB  - Human/mouse chimeric monoclonal antibody (mAb) ch14.18/CHO is directed against
      disialoganglioside GD2. Activity and efficacy of this mAb are currently
      determined in ongoing clinical Phase II and -III studies in high-risk
      neuroblastoma (NB). Based on the chimeric nature of this mAb, some patients may
      develop a human anti-chimeric immune response (Mirick et al., 2004) which impacts
      on pharmacokinetics and may induce anti-anti-idiotype (Id) mAb with a potential
      survival benefit. Therefore, a validated method of quantitative detection of
      human anti-chimeric antibodies (HACA) in serum samples of NB patients treated
      with ch14.18/CHO is an important tool for monitoring of clinical trials. Here, we
      report a validated sandwich enzyme-linked immunosorbent assay (ELISA) according
      to the one arm binding principle using ch14.18/CHO as a capture mAb and
      biotinylated ch14.18/CHO mAb for detection. Ganglidiomab, a monoclonal anti-Id Ab
      to ch14.18/CHO (Lode et al., 2013), was used as a standard for assay validation
      and HACA quantification. Systematic evaluation of the established ELISA procedure
      revealed an optimal serum sample dilution factor of 1:160. Assay validation was
      accomplished with a set of tailored quality controls (QC) containing distinct
      concentrations of ganglidiomab (3 and 15MUg/ml). The coefficients of variation
      (CV) for all within-assay and inter-assay measurements using QCs were under 20%
      and the limit of detection (LOD) was 1.1MUg/ml. Three patients (P1, P2, P3)
      treated with a 10day continuous infusion of 100mg/m(2) of ch14.18/CHO were
      selected for analysis with this assay. Selection was based on ch14.18/CHO drug
      level on day 8 in cycle 2 of >10MUg/ml (expected) (P1) and of <2MUg/ml
      (unexpected) (P2 and P3). Both patients with unexpected low ch14.18/CHO levels
      revealed a strong signal in the HACA ELISA. Interestingly, ch14.18/CHO-mediated
      complement-dependent cytotoxicity (CDC) could not be detected in P2 in contrast
      to P3 suggesting anti-NB activity even in the presence of HACA. We showed that
      neither eight freeze-thaw cycles nor storage at room temperature for up to 168h
      affected HACA stability in serum. In summary, we describe a validated ELISA
      method suitable for the assessment of HACA in NB patients treated with
      ch14.18/CHO. 

PMID- 24727145
TI  - Development of four sandwich ELISAs for quantitation of capsular polysaccharides
      from Neisseria meningitidis serogroups A, C, W and Y in multivalent vaccines.
AB  - Neisseria meningitidis is a Gram negative bacterium that has been classified in
      13 serogroups according to the biochemical composition of the capsular
      polysaccharide (CP). However, invasive infections are most frequently caused by
      six of these serogroups: A, B, C, W, X and Y (MenA, MenB, MenC, MenW, MenX,
      MenY). Individual CP quantitation in multivalent meningococcal CP-based vaccines
      is required for quality control testing of these products. In this regard, four
      sandwich enzyme-linked immunosorbent assays (ELISAs) were developed for the
      quantitation of CP. The quantitation and detection limits of the four ELISAs were
      below 1ng/mL. The assays showed good reproducibility and repeatability as
      calculated for each point of the standard curve (CV<15%). In addition, five
      multivalent meningococcal CP-based vaccines were evaluated and the proposed
      ELISAs showed that these vaccines were found into the accepted range (+/-30%) of
      CP content. These assays are suitable for screening multiple plain or conjugated
      meningococcal CP-based vaccines and could be useful for monitoring lot-to-lot
      consistency and stability analysis. 

PMID- 24727146
TI  - Quantification of peripapillary total retinal volume in pseudopapilledema and
      mild papilledema using spectral-domain optical coherence tomography.
AB  - PURPOSE: To distinguish differences in retinal nerve fiber layer (RNFL) thickness
      and peripapillary total retinal volume between eyes with papilledema,
      pseudopapilledema, and normal findings. DESIGN: Cohort study. METHODS: Forty-two
      eyes with mild papilledema, 37 eyes with congenitally elevated optic disc
      (pseudopapilledema), and 34 normal eyes met the inclusion criteria at 1 academic
      institution (in Iran) and underwent neuro-ophthalmic examination. Spectral-domain
      optical coherence tomography scans surrounding the optic disc were performed in
      each eye of patients and subjects. Main outcome measures were mean RNFL thickness
      and peripapillary total retinal volume measurements (inner and outer ring
      volumes) that were compared between groups, using the generalized estimating
      equation approach. Area under receiver operating characteristic curves were also
      calculated. RESULTS: A statistically significant difference was found in mean
      RNFL thickness between both groups of patients with papilledema and
      pseudopapilledema and normal subjects. Average inner peripapillary total retinal
      volume in the papilledema, pseudopapilledema, and control groups were 1.95 +/-
      0.24 mm(3), 1.81 +/- 0.23 mm(3), and 1.06 +/- 0.10 mm(3), respectively. Average
      outer peripapillary total retinal volume in the papilledema and pseudopapilledema
      groups were 2.68 +/- 0.49 mm(3) and 2.03 +/- 0.24 mm(3), respectively (P < .001).
      However, the outer ring peripapillary total retinal volume was not different
      between pseudopapilledema and normal (1.90 +/- 0.11 mm(3)) eyes (P = .17). Area
      under the curve to discriminate pseudopapilledema vs papilledema eyes for average
      RNFL thickness and inner and outer peripapillary total retinal volumes was 0.82,
      0.68, and 0.88, respectively. CONCLUSION: Outer peripapillary total retinal ring
      volumes might be useful in differentiating papilledema from pseudopapilledema.

PMID- 24727147
TI  - Methods to assess Drosophila heart development, function and aging.
AB  - In recent years the Drosophila heart has become an established model for many
      different aspects of human cardiac disease. This model has allowed identification
      of disease-causing mechanisms underlying congenital heart disease and
      cardiomyopathies and has permitted the study of underlying genetic, metabolic and
      age-related contributions to heart function. In this review we discuss methods
      currently employed in the analysis of the Drosophila heart structure and
      function, such as optical methods to infer heart function and performance,
      electrophysiological and mechanical approaches to characterize cardiac tissue
      properties, and conclude with histological techniques used in the study of heart
      development and adult structure. 

PMID- 24727148
TI  - Ursolic acid protects mouse liver against CCl4-induced oxidative stress and
      inflammation by the MAPK/NF-kappaB pathway.
AB  - Ursolic acid (UA), a natural pentacyclic triterpenoid, has been reported to have
      many benefits and medicinal properties. However, its protective effects against
      carbon tetrachloride (CCl(4)) induced hepatotoxicity have not been clarified. The
      aim of the present study was to investigate the effects of UA on oxidative stress
      and inflammation in liver of CCl(4) treated mice. Male ICR mice were injected
      with CCl(4) with or without UA co-administration (25 and 50 mg/kg
      intragastrically once daily) for one week. Our data showed that UA significantly
      prevented CCl(4)-induced hepatotoxicity in a dose-dependent manner, indicated by
      both diagnostic indicators of liver damage (serum aminotransferase activities)
      and histopathological analysis. Moreover, CCl(4)-induced profound elevation of
      reactive oxygen species (ROS) production and oxidative stress, as evidenced by
      increasing of lipid peroxidation level and depleting of the total antioxidant
      capacity (TAC) level in liver, were suppressed by treatment with UA. Furthermore,
      western blot analysis showed that UA significantly decreased CYP2E1 expression
      levels and production of pro-inflammatory markers including TNF-alpha, IL-1beta
      and COX-2 in CCl(4)-treated mouse liver. In exploring the underlying mechanisms
      of UA action, we found that UA decreased the activation of mitogen-activated
      protein kinases (JNK, p38 MAPK, ERK), which in turn inactivated the
      immunoregulatory transcription factor nuclear factor kappa B (NF-kappaB) in liver
      of CCl(4) treated mice. In conclusion, these results suggested that the
      inhibition of CCl(4)-induced inflammation by UA is due at least in part to its
      anti-oxidant activity and its ability to modulate the MAPK and NF-kappaB
      signaling pathway.

PMID- 24727149
TI  - Transcriptional expression analysis of ABC efflux transporters and xenobiotic
      metabolizing enzymes in the Chinese rare minnow.
AB  - In the present study, the cDNA fragments of five ABC transporter genes (ABCB1,
      ABCB11, ABCC1, ABCC2, and ABCG2) in the rare minnow were cloned, and their tissue
      specific expression patterns were evaluated across eight rare minnow tissues
      (liver, gill, intestine, kidney, spleen, brain, skin, and muscle). Furthermore,
      the transcriptional effects on these ABC transporter genes and five xenobiotic
      metabolizing enzyme genes (CYP1A, GSTm, GSTp1, GCLC, and UGT1a) were determined
      in the rare minnow liver after 12 days of pyrene exposure. Basal expression
      analysis showed that the tissues with high expression of the ABC transporters
      included the liver, kidney, and intestine. Moreover, the most highly expressed of
      the ABC genes were ABCB1 and ABCC2 in all eight of the tissues tested. The ABCB11
      gene was almost exclusively expressed in the liver of the rare minnow, whereas
      ABCC1 and ABCG2 showed weak expression in all eight tissues compared to ABCB1 and
      ABCC2. Our results provide the first thorough examination of the expression
      patterns of toxicologically relevant ABC transporters in the rare minnow and
      serve as a necessary basis for further studies of these ABC transporters in fish.
      Furthermore, synergistic up-regulation of CYP1A, GSTp1, GCLC, UGT1a, and ABCC2
      was observed in the rare minnow liver following pyrene exposure, while GSTm,
      ABCB1, ABCB11, ABCC1, and ABCG2 were not significantly affected (p < 0.05). The
      synergistic up-regulation of the xenobiotic-metabolizing enzymes and ABC
      transporters by pyrene suggests a possible involvement and cooperation of these
      genes in the detoxification process in rare minnows.

PMID- 24727151
TI  - Susac's syndrome--pathogenesis, clinical variants and treatment approaches.
AB  - Susac's syndrome is a rare disease that is characterised by the clinical triad of
      encephalopathy, branch retinal artery occlusion, and sensorineural hearing loss.
      It was first described as a distinctive syndrome by Susac in 1979. There have
      been 304 reported individual patients with Susac's syndrome. Etiopathogenesis is
      not clear, although it is now thought that it is an immune-mediated
      endotheliopathy that affects the microvasculature of the brain, retina, and inner
      ear. Antiendothelial cell antibodies (AECAs) play an important role in mediating
      the endothelial cell injury with consequent deposition of thrombotic material in
      the lumen of the small vessel. In biopsies of the brain, microinfarcts with
      atrophy of the white and grey matter could be detected. These microinfarcts are
      caused by a microangiopathic process with arteriolar wall proliferation,
      lymphocytic infiltration and basal lamina thickening. At clinical onset, the most
      common manifestation was central nervous system symptoms, followed by visual
      symptoms and hearing disturbances. Diagnosis is based on Magnetic Resonance
      Imaging (MRI), retinal fluorescein angiography, and audiometry; these are
      considered crucial tests to enable diagnosis. Antiendothelial cell antibodies
      (AECAs) are also of diagnostic relevance. Based on the hypothesis of being an
      autoimmune disease, treatment has to be immunosuppressive. In addition,
      anticoagulation measures, antiplatelet agents and antivasospastic agents should
      be considered. The majority of patients did not initially present with the
      complete triad of symptoms. An appropriate approach would be to perform a search
      for absent components of the triad if the clinical presentation is suggestive of
      Susac's syndrome. Improved understanding of the presentation of Susac's syndrome
      will prevent misdiagnosis and ensure that patients receive the best possible
      care. 

PMID- 24727150
TI  - Commensal bacteria mediated defenses against pathogens.
AB  - Commensal bacterial communities residing within the intestinal lumen of mammals
      have evolved to flourish in this microenvironment. To preserve this niche,
      commensal bacteria act with the host to prevent colonization by invasive
      pathogens that induce inflammation and disrupt the intestinal niche commensal
      bacteria occupy. Thus, it is mutually beneficial to the host and commensal
      bacteria to inhibit a pathogen's ability to establish an infection. Commensal
      bacteria express factors that support colonization, maximize nutrient uptake, and
      produce metabolites that confer a survival advantage over pathogens. Further,
      commensal bacteria stimulate the host's immune defenses and drive tonic
      expression of anti-microbial factors. In combination, these mechanisms preserve
      the niche for commensal bacteria and assist the host in preventing infection. 

PMID- 24727153
TI  - Molecular cloning, tissue distribution and expression analysis of a manganese
      superoxide dismutase in blunt snout bream Megalobrama amblycephala.
AB  - The full-length mitochondrial manganese superoxide dismutase cDNA of blunt snout
      bream Megalobrama amblycephala (denoted as MamMnSOD) was identified in liver
      using homology cloning and rapid amplification of cDNA ends. The full-length cDNA
      of MamMnSOD consisted of 986 bp, with an open reading frame encoding 224 amino
      acids, a 58-bp 5' untranslated region and a 256-bp 3' untranslated region. The
      deduced amino acid sequences of MamMnSOD showed high sequence homology to
      mitochondrial MnSODs from crustaceans. Several motifs, including three
      mitochondrial MnSOD signatures, amino acid residues responsible for coordinating
      the manganese, and the putative active center, were almost completely conserved
      in the deduced amino acid sequences of MamMnSOD. The mRNA expression of MamMnSOD
      in the tissues of heart, liver, spleen, kidney, muscle, intestine, and gill was
      examined by quantitative real-time PCR; the highest expression was in the liver.
      Transcription of MamMnSOD was kinetically modulated in response to nitrite stress
      in liver and gill tissues. The purified recombinant MamMnSOD showed potent
      antioxidant activity. Polyclonal antibodies generated from the recombinant
      product of MamMnSOD were used to specifically identify the native protein in
      liver of M. amblycephala. Collectively, the findings of this study strongly
      suggested that MamMnSOD combats oxidative stress and cellular damage induced by
      nitrite, by detoxifying harmful reactive oxygen species in M. amblycephala. 

PMID- 24727154
TI  - Circulating levels of neuropeptide proenkephalin A predict outcome in patients
      with aneurysmal subarachnoid hemorrhage.
AB  - High plasma proenkephalin A level has been associated with ischemic stroke
      severity and clinical outcomes. This study aimed to assess the relationship
      between proenkephalin A and disease severity as well as to investigate its
      ability to predict long-term clinical outcome in patients with aneurysmal
      subarachnoid hemorrhage. Plasma proenkephalin A concentrations of one hundred and
      eighty patients and 180 sex- and age-matched healthy controls were measured by
      chemoluminescence sandwich immunoassay. Plasma proenkephalin A level was
      substantially higher in patients than in healthy controls (205.5+/-41.6 pmol/L
      vs. 90.8+/-21.1 pmol/L, P<0.001), was highly associated with World Federation of
      Neurological Surgeons (WFNS) score (r=0.470, P<0.001) and Fisher score (r=0.488,
      P<0.001), was an independent predictor for 6-month mortality [odds ratio (OR),
      1.183; 95% confidence interval (CI), 1.067-1.339; P=0.004] and unfavorable
      outcome (Glasgow Outcome Scale score of 1-3) (OR, 1.119; 95% CI, 1.046-1.332;
      P=0.005) using multivariate analysis, and had high area under receiver operating
      characteristic curve (AUC) for prediction of 6-month mortality (AUC, 0.831; 95%
      CI, 0.768-0.883) and unfavorable outcome (AUC, 0.821; 95% CI, 0.757-0.874). The
      predictive value of the plasma proenkephalin A concentration was also similar to
      those of WFNS score and Fisher score (both P>0.05). In a combined logistic
      regression model, proenkephalin A improved the AUCs of WFNS score and Fisher
      score, but the differences were not significant (both P>0.05). Thus,
      proenkephalin A level may be a useful, complementary tool to predict mortality
      and functional outcome at 6 months after aneurysmal subarachnoid hemorrhage.

PMID- 24727155
TI  - A novel self-cleavage system for production of soluble recombinant protein in
      Escherichia coli.
AB  - Many approaches for generating large quantities of recombinant protein in
      Escherichia coli fuse the protein of interest to a protein tag to enhance
      solubility and improve recovery. However, the fusion tags can confound downstream
      applications, as the fusion partner can alter the structure and biological
      activity of the recombinant protein and proteolytic removal of the fusion tags
      can be expensive. Here we describe a new system for production of native proteins
      in E. coli that allows for removal of the fusion tag via intracellular self
      cleavage by the human rhinovirus 3C (HRV3C) protease. This system allows for
      parallel cloning of target protein coding sequences into six different expression
      vectors, each with a different fusion partner tag to enhance solubility during
      induction. Temperature-regulated expression of the HRV3C protease allows for
      intracellular removal of the fusion tag following induction, and the liberated
      recombinant protein can be purified by affinity chromatography by virtue of a
      short six-histidine tag. This system will be an attractive approach for the
      expression and purification of recombinant proteins free of solubility-enhancing
      fusion tags, and should be amenable to high-throughput applications. 

PMID- 24727156
TI  - Efficient production and purification of extracellular domain of human FGFR-Fc
      fusion proteins from Chinese hamster ovary cells.
AB  - The family of fibroblast growth factor receptors (FGFRs) plays an important role
      in cell growth, survival, differentiation and angiogenesis. The three
      immunoglobulin-like extracellular domains of FGFR (D1, D2, and D3) are critical
      for ligand binding and specificity towards fibroblast growth factor and heparan
      sulfate. Fibroblast growth factor receptors are overexpressed in a wide variety
      of tumors, such as breast, bladder, and prostate cancer, and therefore they are
      attractive targets for different types of anticancer therapies. In this study, we
      have cloned, expressed in CHO cells and purified Fc-fused extracellular domains
      of different types of FGFRs (ECD_FGFR1a-Fc, ECD_FGFR1b-Fc, ECD_FGFR2a-Fc,
      ECD_FGFR2b-Fc, ECD_FGFR3a-Fc, ECD_FGFR3b-Fc, ECD_FGFR4a-Fc, ECD_FGFR4b-Fc), which
      could be used as molecular targets for the selection of specific antibodies. The
      fusion proteins were analyzed using gel electrophoresis, Western blotting and
      mass spectrometry. To facilitate their full characterization, the fusion proteins
      were deglycosylated using PNGase F enzyme. With an optimized transient
      transfection protocol and purification procedure we were able to express the
      proteins at a high level and purify them to homogeneity. 

PMID- 24727157
TI  - Transglutaminase 2 on the surface of dendritic cells is proposed to be involved
      in dendritic cell-T cell interaction.
AB  - Transglutaminase 2 (TG2) is a ubiquitous enzyme involved in diverse biological
      processes. Recently, its function in adaptive immune responses has begun to
      emerge. Its presence and functions in B cells and T cells, for example, have been
      reported. However, those in dendritic cells (DCs), the principal antigen
      presenting cells, are as yet unexplored in murine system. In this study, we first
      investigated the expression of TG2 in murine bone marrow-derived DCs, and then
      compared the functioning of these cells in the presence or absence of this enzyme
      using wild-type (WT) and TG2(-/-) mice. We found that the WT DCs expressed TG2
      both in the cytoplasm and on the cell surface, both of which were elevated after
      LPS stimulation. Unexpectedly, between WT and TG2(-/-) DCs, there were no
      remarkable differences in cytokine secretion, IL-10 and IL-12, and neither in the
      expression of surface molecules CD80, CD86, and MHC II, excepting a moderate
      decrease of CD40 expression on the TG2(-/-) DCs. However, when T cells were
      stimulated with TG2(-/-) DCs, they showed decreased levels of proliferation, CD69
      and CD25 expression, and IFN-gamma secretion. The addition of anti-TG2 antibody
      to the WT DC-T cell co-culture resulted in decreased T cell activation. By
      immunofluorescence staining, TG2 was observed at DC-T cell interface (contact
      point). Taken together, we propose that TG2 on the surface of DCs modulates the
      DC-T cell interaction. 

PMID- 24727158
TI  - Telomeres and telomerase in T cells of tumor immunity.
AB  - Telomeres are specific nucleoprotein structures at the end of a eukaryotic
      chromosomes characterized by repeats of the sequence TTAGGG and regulated by the
      enzyme telomerase which prevents their degradation, loss, rearrangement and end
      to-end fusion. During activation, T lymphocytes actively divide, albeit through
      only a finite number of cell divisions due to shortening of telomeres. However,
      studies have demonstrated that human telomerase reverse transcriptase (hTERT),
      thought to be the major component regulating telomerase activity, can enhance the
      proliferation of T cells when overexpressed. There are many treatments for
      cancers, most of which are targeting the telomere and telomerase of tumor cells.
      However, the hTERT-transduced T cells improve their potential for proliferation,
      making them an appropriate cell resource for tumor adoptive immunotherapy, a
      procedure whereby T cells are isolated from patients, expanded ex vivo and
      eventually delivered back into the patients, provides a new approach for tumor
      therapy through improved overall survival rates in cancer patients. In this
      review, we will focus on the telomerase activity in T cells, the regulation of
      telomerase activity, and hTERT-transduced T cells used in adoptive immunotherapy
      for cancer. 

PMID- 24727159
TI  - Infant cynomolgus monkeys exposed to denosumab in utero exhibit an osteoclast
      poor osteopetrotic-like skeletal phenotype at birth and in the early postnatal
      period.
AB  - RANKL is a key regulator of bone resorption and osteoclastogenesis. Denosumab is
      a fully human IgG2 monoclonal antibody that inhibits bone resorption by binding
      and inhibiting the activity of RANKL. To determine the effects of denosumab on
      pre- and postnatal skeletal growth and development, subcutaneous injections of 0
      (control) or 50 mg/kg/month denosumab were given to pregnant cynomolgus monkeys
      from approximately gestation day (GD) 20 until parturition (up to 6 doses). For
      up to 6 months postpartum (birth day [BD] 180/181), evaluation of the infants
      included skeletal radiographs, bone biomarkers, and oral examinations for
      assessment of tooth eruption. Infant bones were collected at necropsy for
      densitometry, biomechanical testing, and histopathologic evaluation from control
      and denosumab-exposed infants on BD1 (or within 2 weeks of birth) and BD181, and
      from infants that died or were euthanized moribund from BD5 to BD69. In all
      denosumab-exposed infants, biomarkers of bone resorption and formation were
      markedly decreased at BD1 and BD14 and slightly greater at BD91 vs. control, then
      similar to control values by BD181. Spontaneous long bone fractures were detected
      clinically or radiographically in 4 denosumab-exposed infants at BD28 and BD60,
      with evidence of radiographic healing at >=BD60. In BD1 infants exposed to
      denosumab in utero, radiographic evaluations of the skeleton revealed decreased
      long bone length; a generalized increased radio-opacity of the axial and
      appendicular skeleton and bones at the base of the skull with decreased or absent
      marrow cavities, widened growth plates, flared/club-shaped metaphysis, altered
      jaw/skull shape, and reduced jaw length; and delayed development of secondary
      ossification centers. Densitometric evaluations in these infants demonstrated a
      marked increase in bone mineral density at trabecular sites, but cortical bone
      mineral density was decreased. Histologically, long bone cortices were attenuated
      and there was an absence of osteoclasts. Bones with active endochondral
      ossification consisted largely of a dense network of retained primary spongiosa
      with reduced marrow space consistent with an osteopetrotic phenotype. A minimal
      increase in growth plate thickness largely due to the expansion of the
      hypertrophic zone was present. Retained woven bone was observed in bones formed
      by intramembranous ossification, consistent with absence of bone remodeling.
      These changes in bone tissue composition and geometry were reflected in reduced
      biomechanical strength and material properties of bones from denosumab-exposed
      infants. Material property changes were characterized by increased tissue
      brittleness reflected in reductions in calculated material toughness at the femur
      diaphysis and lack of correlation between energy and bone mass at the vertebra;
      these changes were likely the basis for the increased skeletal fragility
      (fractures). Although tooth eruption was not impaired in denosumab-exposed
      infants, the reduced growth and increased bone density of the mandible resulted
      in dental abnormalities consisting of tooth malalignment and dental dysplasia.
      Radiographic changes at BD1 persisted at BD28, with evidence of resumption of
      bone resorption and remodeling observed in most infants at BD60 and/or BD90. In 2
      infants euthanized on BD60 and BD69, there was histologic and radiographic
      evidence of subphyseal/metaphyseal bone resorption accompanied by multiple foci
      of ossification in growth plates that were markedly increased in thickness. In
      infants necropsied at BD181, where systemic exposure to denosumab had been below
      limits of quantitation for approximately 3months, there was largely full recovery
      from all bone-related changes observed earlier postpartum, including tissue
      brittleness. Persistent changes included dental dysplasia, decreased bone length,
      reduced cortical thickness, and decreased peak load and ultimate strength at the
      femur diaphysis. In conclusion, the skeletal and secondary dental effects
      observed in infant monkeys exposed in utero to denosumab are consistent with the
      anticipated pharmacological activity of denosumab as a monoclonal antibody
      against RANKL and inhibitor of osteoclastogenesis. The resulting inhibition of
      resorption impaired both bone modeling and remodeling during skeletal development
      and growth. The skeletal phenotype of these infant monkeys resembles human
      infants with osteoclast-poor osteopetrosis due to inactivating mutations of RANK
      or RANKL.

PMID- 24727160
TI  - The effects of once-weekly teriparatide on hip geometry assessed by hip
      structural analysis in postmenopausal osteoporotic women with high fracture risk.
AB  - Weekly administration of teriparatide has been shown to reduce the risk of
      vertebral and non-vertebral fractures in patients with osteoporosis at higher
      fracture risk in Japan. However, its efficacy for hip fracture has not been
      established. To gain insight into the effect of weekly teriparatide on the hip,
      hip structural analysis (HSA) based on dual-energy X-ray absorptiometry (DXA) was
      performed using the data of 209 postmenopausal osteoporotic women who had
      participated in the original randomized, multicenter, double-blind, placebo
      controlled trial assessing the effects of once-weekly 56.5 MUg teriparatide for
      72 weeks. The DXA scans, obtained at baseline, 48 weeks and 72 weeks, were
      analyzed to extract bone mineral density (BMD) and cross-sectional geometrical
      indices at the narrowest point on the neck (NN), the intertrochanteric region
      (IT), and the proximal shaft. Compared with placebo after 72 weeks, the
      teriparatide group showed significantly higher BMD, average cortical thickness,
      bone cross-sectional area, and section modulus, and lower buckling ratio at both
      the NN and IT regions. No significant expansion of periosteal diameter was
      observed at these regions. There were no significant differences in BMD and HSA
      indices at the shaft region. The results indicate that overall structural
      strength in the proximal femur increased compared to placebo, suggesting that
      once-weekly teriparatide effectively reverses changes in hip geometry and
      strength with aging.

PMID- 24727161
TI  - Peroxisomal dysfunction is associated with up-regulation of apoptotic cell death
      via miR-223 induction in knee osteoarthritis patients with type 2 diabetes
      mellitus.
AB  - Recent increasing evidences showing the interconnection between mitochondria and
      peroxisome in performing metabolic functions imply that peroxisome dysfunction
      could lead to a wide variety of human diseases including cancer and
      osteoarthritis (OA) as mitochondria dysfunction. Even though there is a higher
      incidence and development of OA in diabetes mellitus (DM) patients, there is not
      much evidential mechanism study in this inter-regulation between OA and OA with
      DM in a new view of peroxisome. In this study, we analyzed the alteration of
      peroxisomal gene expression that could responsible for pathological difference
      between OA chondrocytes and OA/DM chondrocytes. To discriminate responsible genes
      in the OA/DM pathogenesis, the expressions of three hundred sixty-two genes
      reported to differentially relate to peroxisome were analyzed with OA
      chondrocytes in OA cartilage and OA/DM chondrocytes in the cartilage of OA with
      DM patient. Among them, PEX-16, a component of peroxisome, was significantly down
      regulated in OA/DM chondrocytes and this down-regulation of PEX-16 increased the
      miR-223 induction. Knockdown studies using PEX-16 null cell line and PEX-16
      specific siRNA showed the significant increase in apoptotic cell death. Moreover,
      over-expression of miR-223 stimulates apoptotic cell death in human articular
      chondrocytes and induced severe cartilage destruction in db/db mice. In
      conclusion, our study showed the differential peroxisomal gene expression
      profiles for OA/DM chondrocytes from OA chondrocytes and suggests the possibility
      that peroxisomal dysfunction in OA/DM could be responsible for early incidence
      and development of OA in DM patients. 

PMID- 24727162
TI  - Effect of combined teriparatide and monthly minodronic acid therapy on cancellous
      bone mass in ovariectomized rats: a bone histomorphometry study.
AB  - The purpose of the present study was to determine whether teriparatide and
      monthly minodronic acid would have an additive effect on cancellous bone mass in
      ovariectomized rats. Seven-week-old female Sprague-Dawley rats were randomized
      into five groups of 10 animals each, including a sham-operation+vehicle group, an
      ovariectomy (OVX)+vehicle group, an OVX+minodronic acid (6 MUg/kgs.c., every 4
      weeks) group, an OVX+teriparatide (20 MUg/kgs.c., daily) group, and an
      OVX+minodronic acid+teriparatide group. After the 12-week experimental period,
      static and dynamic histomorphometric analyses were performed on the cancellous
      bone of the tibial proximal metaphysis. OVX decreased the bone volume per total
      volume (BV/TV) and the trabecular number (Tb.N) and increased the trabecular
      separation (Tb.Sp) as a result of increased bone remodeling. Minodronic acid
      prevented the OVX-induced decreases in BV/TV, while teriparatide increased the
      BV/TV and trabecular width (Tb.Wi) beyond the values of the sham controls.
      Minodronic acid prevented, but teriparatide only mitigated, the OVX-induced
      decrease in Tb.N, although both drugs similarly prevented the OVX-induced
      increase in Tb.Sp. A combination of teriparatide and minodronic acid further
      increased the BV/TV and Tb.N and decreased the Tb.Sp as a result of the
      suppression of bone remodeling, compared with teriparatide alone. These results
      suggest the differential effect of teriparatide and monthly minodronic acid on
      cancellous bone structure and the additive effect of the two drugs on cancellous
      bone mass in OVX rats.

PMID- 24727163
TI  - Quantum chemical computations, vibrational spectroscopic studies, NLO and
      NBO/NLMO analysis of o-chlorobenzohydrazide.
AB  - The molecular vibrations of o-chlorobenzohydrazide (OCBH) have been investigated
      in polycrystalline sample, at room temperature, by recording Fourier transform
      infrared (FT-IR) and FT-Raman spectroscopies. The complete vibrational assignment
      and analysis of the fundamental modes was carried out using the experimental data
      and quantum chemical studies. The observed vibrational data were compared with
      the wavenumbers derived theoretically for the optimized geometry of the compound
      from the HF and DFT/B3LYP calculations employing 6-311++G(d,p) basis set. The
      (1)H and (13)C NMR chemical shifts have been simulated. Thermodynamic properties
      have been calculated at different temperatures. HOMO-LUMO energy gap has been
      calculated. The intramolecular contacts have been interpreted using Natural Bond
      Orbital (NBO) and Natural Localized Molecular Orbital (NLMO) analysis. 

PMID- 24727164
TI  - DFT study of conformational and vibrational characteristics of 2-(2
      hydroxyphenyl)benzothiazole molecule.
AB  - The conformational and IR and Raman spectral studies of 2-(2
      hydroxyphenyl)benzothiazole have been carried out by using the DFT method at the
      B3LYP/6-311++G(**) level. The detailed vibrational assignments have been done on
      the basis of calculated potential energy distributions. Comparative studies of
      molecular geometries, atomic charges and vibrational fundamentals of all the
      conformers have been made. There are four possible conformers for this molecule.
      The optimized geometrical parameters obtained by B3LYP/6-311++G(**) method showed
      good agreement with the experimental X-ray data. The atomic polar tensor (APT)
      charges, Mulliken atomic charges, natural bond orbital (NBO) analysis and HOMO
      LUMO energy gap of HBT and its conformers were also computed. 

PMID- 24727165
TI  - DFT calculation and vibrational spectroscopic studies of 2-(tert-butoxycarbonyl
      (Boc) -amino)-5-bromopyridine.
AB  - The molecular structure of 2-(tert-butoxycarbonyl (Boc) -amino)-5-bromopyridine
      (BABP) was optimized by the DFT/B3LYP method with 6-311G (d,p), 6-311++G (d,p)
      and cc-pVTZ basis sets using the Gaussian 09 program. The most stable optimized
      structure of the molecule was predicted by the DFT/B3LYP method with cc-pVTZ
      basis set. The vibrational frequencies, Mulliken atomic charge distribution,
      frontier molecular orbitals and thermodynamical parameters were calculated. These
      calculations were done at the ground state energy level of BABP without applying
      any constraint on the potential energy surface. The vibrational spectra were
      experimentally recorded using Fourier Transform-Infrared (FT-IR) and micro-Raman
      spectrometer. The computed vibrational frequencies were scaled by scale factors
      to yield a good agreement with observed experimental vibrational frequencies. The
      complete theoretically calculated and experimentally observed vibrational
      frequencies were assigned on the basis of Potential Energy Distribution (PED)
      calculation using the VEDA 4.0 program. The vibrational modes assignments were
      performed by using the animation option of GaussView 05 graphical interface for
      Gaussian program. The Mulliken atomic charge distribution was calculated for BABP
      molecule. The molecular reactivity and stability of BABP were also studied by
      frontier molecular orbitals (FMOs) analysis. 

PMID- 24727166
TI  - Analytical studies on the charge transfer complexes of loperamide hydrochloride
      and trimebutine drugs. Spectroscopic and thermal characterization of CT
      complexes.
AB  - Charge transfer complexes of loperamide hydrochloride (LOP.HCl) and trimebutine
      (TB) drugs as electron donor with 2,3-dichloro-5,6-dicyano-p-benzoquinone (DDQ),
      tetracyanoethylene (TCNE) and 7,7,8,8-tetracyanoquinodimethane (TCNQ) as pi
      acceptors in acetonitrile were investigated spectrophotometrically to determine
      the cited drugs in pure and dosage forms. The reaction gives highly coloured
      complex species which are measured spectrophotometrically at 460, 415 and 842nm
      in case of LOP.HCl and at 455, 414 and 842nm in case of TB using DDQ, TCNE and
      TCNQ reagents, respectively. The optimum experimental conditions have been
      studied carefully and optimized. Beer's law was obeyed over the concentration
      ranges of 47.70-381.6, 21.50-150.5 and 10.00-100.0MUgmL(-1) for LOP.HCl and 37.85
      264.9, 38.75-310.0 and 7.75-155.0MUgmL(-1) for TB using DDQ, TCNE and TCNQ
      reagents, respectively. Sandell sensitivity, standard deviation, relative
      standard deviation, limit of detection and quantification were calculated. The
      obtained data refer to high accuracy and precision of the proposed method. These
      results are also confirmed by inter and intra-day precision with percent recovery
      of 99.18-101.1% and 99.32-101.4% in case of LOP.HCl and 98.00-102.0% and 97.50
      101.4% in case of TB using DDQ, TCNE and TCNQ reagents for intra- and inter-day,
      respectively. These data were compared with those obtained using official methods
      for the determination of the cited drugs. The stability constants of the CT
      complexes were determined. The final products of the reaction were isolated and
      characterized using FT-IR, (1)H NMR, elemental analysis and thermogravimetric
      analysis (TG). The stoichiometry and apparent formation constant of the complexes
      formed were determined by applying the conventional spectrophotometric molar
      ratio method. 

PMID- 24727167
TI  - Synthesis, characterization and antibacterial activity of a Schiff base derived
      from cephalexin and sulphathiazole and its transition metal complexes.
AB  - Metal(II) coordination compounds of a cephalexin Schiff base (HL) derived from
      the condensation of cephalexin antibiotic with sulphathiazole were synthesized.
      The Schiff base ligand, mononuclear [ML(OAc)(H2O)2] (M(II)=Mn, Co, Ni, Zn)
      complexes and magnetically diluted trinuclear copper(II) complex [Cu3L(OH)5] were
      characterized by several techniques, including elemental and thermal analysis,
      molar conductance and magnetic susceptibility measurements, electronic, FT-IR,
      EPR and (1)H NMR spectral studies. The analytical and molar conductance values
      indicated that the acetate ions coordinate to the metal ions. The Schiff base
      ligand HL behaves as a monoanionic tridentate NNO and tetradentate NNOO chelating
      agent in the mono and trinuclear complexes respectively. 

PMID- 24727168
TI  - Synthesis, characterization and reactivity of trinuclear Cu(II) complexes derived
      from disalicylaldehyde malonoyldihydrazone.
AB  - Three new homotrinuclear copper(II) complexes [Cu3(slmh)(MU
      Cl)2(CH3OH)3]?0.5CH3OH (1), [Cu3(slmh)(NO3)2(CH3OH)5]?1.5CH3OH (2) and
      [Cu3(slmh)(MU-ClO4)2(CH3OH)3]?2CH3OH (3) from disalicylaldehyde
      malonoyldihydrazone have been synthesized and characterized. The composition of
      the complexes has been established on the basis of data obtained from analytical
      and thermoanalytical data. The structure of the complexes has been discussed in
      the light of molar conductance, electronic, FT-IR and far-IR spectral data,
      magnetic moment and EPR spectral studies. The molar conductance values for the
      complexes in DMSO solution indicate that all of them are non-electrolyte. The
      magnetic moment values for the complexes suggest considerable metal-metal
      intramolecular interaction between metal ions in the structural unit of the
      complexes. The EPR spectral features reveal that at RT, the ground state for the
      complexes is a mixture of the quartet state (S=3/2) and doublet state (S=1/2). At
      lower temperature, the ground state for the complexes is dx(2)-y(2) with
      considerable contribution from dz(2) orbital. Dihydrazone ligand is present in
      enol form in all of the complexes. The complexes have distorted square pyramidal
      stereochemistry. The electron transfer reactions of the complexes have been
      investigated by cyclic voltammetry. Hydrogen peroxide mediated oxidation of
      benzyl alcohol catalyzed by complex 1 has been studied.

PMID- 24727169
TI  - Investigations on the vibrational modes and non-linear optical properties of 4
      Fluoro Chalcone crystal.
AB  - Organic Nonlinear Optical (NLO) crystals of 4-fluorochalcone (4FC) were
      synthesized and grown by slow evaporation solution growth method. The grown
      crystals have been characterised by powder X-ray diffraction, factor group
      analysis, FTIR, FT-Raman, UV-Vis Spectroscopy, powder SHG and Vickers
      microhardness tests. Theoretical quantum chemical analysis were performed to
      determine the first order hyperpolarizability (beta) and HOMO-LUMO analysis of
      the title compound were computed by GAUSSIAN 03 package. 

PMID- 24727170
TI  - Biosynthesis, characterization and antibacterial studies of silver nanoparticles
      using pods extract of Acacia auriculiformis.
AB  - The present study reports an environmental friendly method for the synthesis of
      silver nanoparticles (Ag NPs) using an aqueous extract of Acacia auriculiformis
      that acts as reducing agent as well as capping agent. The obtained NPs were
      characterized by UV-vis absorption spectroscopy and showed a sharp surface
      plasmon absorption band at ~400 nm. Fourier transform infrared spectroscopy
      (FTIR) showed nanoparticles were capped with plant compounds. Transmission
      electron microscopy (TEM) showed that the particles were spherical in nature with
      diameter ranging from 20 to 150 nm depending on the pH of the solution. The as
      synthesized Ag NPs showed antibacterial activity against both Gram negative and
      Gram positive bacteria with more efficacy against Gram negative bacteria.

PMID- 24727172
TI  - Experimental Raman and IR spectral and theoretical studies of vibrational
      spectrum and molecular structure of Pantothenic acid (vitamin B5).
AB  - Vibrational spectrum of Pantothenic acid has been investigated using experimental
      IR and Raman spectroscopies and density functional theory methods available with
      the Gaussian 09 software. Vibrational assignments of the observed IR and Raman
      bands have been proposed in light of the results obtained from computations. In
      order to assign the observed IR and Raman frequencies the potential energy
      distributions (PEDs) have also been computed using GAR2PED software. Optimized
      geometrical parameters suggest that the overall symmetry of the molecule is C1.
      The molecule is found to possess eight conformations. Conformational analysis was
      carried out to obtain the most stable configuration of the molecule. In the
      present paper the vibrational features of the lowest energy conformer C-I have
      been studied. The two methyl groups have slightly distorted symmetries from C3V.
      The acidic OH bond is found to be the smallest one. To investigate molecular
      stability and bond strength we have used natural bond orbital analysis (NBO).
      Charge transfer occurs in the molecule have been shown by the calculated highest
      occupied molecular orbital-lowest unoccupied molecular orbital (HOMO-LUMO)
      energies. The mapping of electron density iso-surface with electrostatic
      potential (ESP), has been carried out to get the information about the size,
      shape, charge density distribution and site of chemical reactivity of the
      molecule. 

PMID- 24727171
TI  - Synthesis, crystal structures, luminescence properties of two metal coordination
      polymers derived from 5-substituted isophthalate and flexible bis (triazole)
      ligands.
AB  - Two new metal complexes, [Ni(btx)(nip)(H2O)]n (1), {[Cd(btx)(mip)(H2O)].H2O}n (2)
      (btx=1,4-bis(1,2,4-triazol-1-ylmethyl)benzene, H2nip=5-nitroisophthalic acid,
      H2mip=5-methyisophthalic acid) were synthesized under hydrothermal conditions and
      characterized by single-crystal X-ray diffraction methods, IR spectroscopy, TGA
      and elemental analysis. Complex 1 features a 3D metal-organic framework with
      three-fold interpenetrating CdSO4-type topology. Complex 2 exhibits a 2D network
      with square grid units, which is further extended into a rare 3,5T1 three
      dimensional supramolecular network via three modes of classical OH?O hydrogen
      bonds. In addition, luminescence properties of 1 and 2 have also been
      investigated in the solid state. 

PMID- 24727173
TI  - The investigation on the pressure-induced phase transition in linoleic acid by in
      situ Raman spectroscopy.
AB  - With diamond anvil cell as a high-pressure apparatus, the in situ Raman spectra
      of linoleic acid from normal pressure to 1.29 GPa were measured to investigate
      the effect of pressure on the structural changes. In the pressure ranges of 0.07
      0.12 GPa and 0.31-0.53 GPa, the significant changes in Raman spectra show that
      linoleic acid undergoes two pressure-induced phase transitions. Spectral analysis
      indicates that the polymethylene chain of linoleic acid molecule transforms from
      the disordered gauche conformation to the ordered trans conformation in the range
      of 0.07-0.12 GPa. And the polymethylene chain of linoleic acid molecule remains
      the ordered trans conformation whereas the conformation of the olefin group
      significantly changes and the degree of conformational order increases in the
      range of 0.31-0.53 GPa. The pressure-induced phase transitions in linoleic acid
      are reversible.

PMID- 24727174
TI  - Rotational isomerism of some chloroacetamides: theoretical and experimental
      studies through calculations, infrared and NMR.
AB  - The geometries involved in the conformational equilibria of 2,2-dichloro-N
      cyclohexyl-N-methyl-acetamide (DCCMA) and 2-chloro-N,N-dicyclohexylacetamide
      (CDCA) were investigated. Theoretical calculations at the B3LYP/cc-pVDZ level of
      theory showed that gauche forms (ClCCO) are the most stable and the predominant
      conformers in isolated phase. Both compounds had the conformational behavior in
      solvents of different polarities estimated from theoretical calculations with the
      PCM (Polarizable Continuum Model), at the same level of theory, using infrared
      data from deconvolution of the carbonyl absorption bands and (13)C NMR spectra.
      Their IR spectra showed two carbonyl absorptions and that the conformer with the
      highest dipole moment had its population increased when the most polar solvents
      were used, in accordance with the theoretical calculation in solution. (1)JCH
      coupling constants were obtained from their NMR spectra, and revealed that there
      was population variation of conformers with solvent exchange. Experimental data
      (NMR and IR) as well as calculations including the solvent effects followed the
      same trend. 

PMID- 24727175
TI  - Supramolecular aggregates formed by sulfadiazine and sulfisomidine inclusion
      complexes with alpha- and beta-cyclodextrins.
AB  - Sulfadiazine (SDA) and sulfisomidine (SFM) inclusion complexes with two
      cyclodextrins (alpha-CD and beta-CD) are studied in aqueous as well as in solid
      state. The inclusion complexes are characterized by UV-visible, fluorescence,
      time correlated single photon counting, FTIR, DSC, PXRD and (1)H NMR techniques.
      The self assembled SDA/CD and SFM/CD inclusion complexes form different types of
      nano and microstructures. The self assembled nanoparticle morphologies are
      studied using SEM and TEM techniques. SDA/alpha-CD complex is formed hierarchal
      morphology, SDA/beta-CD and SFM/beta-CD complexes form the nanosheet self
      assembly. However, SFM/alpha-CD complex forms nanoporous sheet self assembly. van
      der Waals, hydrophobic and hydrogen bonding interaction play a vital role in the
      self assembling process. 

PMID- 24727176
TI  - Synthesis, spectral characterization and biological evaluation of Mn(II), Co(II),
      Ni(II), Cu(II), Zn(II) and Cd(II) complexes with thiosemicarbazone ending by
      pyrazole and pyridyl rings.
AB  - Here we present the synthesis of the new Mn(II), Co(II), Ni(II), Cu(II), Zn(II)
      and Cd(II) complexes with chelating ligand (Z)-(2-((1,3-diphenyl-1H-pyrazol-4
      yl)methylene) hydrazinyl)(pyridin-2-ylamino)methanethiol. All the complexes were
      characterized by elemental analysis, IR, (1)H NMR, UV-vis, magnetic
      susceptibility measurements and EPR spectral studies. IR spectra of complexes
      showed that the ligand behaves as NN neutral bidentate, NSN mononegative
      tridentate and NSNN mononegative tetradentate. The electronic spectra and the
      magnetic measurements suggested the octahedral geometry for all complexes as well
      as the EPR confirmed the tetragonal distorted octahedral for Cu(II) complex.
      Cd(II) complex showed the highest inhibitory antioxidant activity either using
      ABTS method. The SOD-like activity exhibited those Cd(II) and Zn(II) complexes
      have strong antioxidative properties. We tested the synthesized compounds for
      antitumor activity and showed that the ability to kill liver (HePG2) and breast
      (MCF-7) cancer cells definitely. 

PMID- 24727177
TI  - On the origins of the absorption spectroscopy of pterin and Re(CO)3(pterin)(H2O)
      aqueous solutions. A combined theoretical and experimental study.
AB  - The origins of the absorption spectroscopy of pterin and Re(CO)3(pterin)(H2O)
      complex as a function of pH is studied using the hybrid functional B3LYP and PBE0
      in combination with 6-311++G(d,p) and LanL2TZ(f) basis sets. A natural bond
      analysis was performed to the principal molecular orbitals involved in the
      electronic transitions of the studied compounds. The low energy band of pterin,
      which is described as a H->L electronic transition, can be interpreted as an
      admixture of pi->pi(*), n->pi(*) and n->n electronic transitions involving pi(C2
      N1, C6-N5, C9-C10) and n(C2) orbitals of the HOMO and pi(*)(C6-N5, C7-N8) and
      n(C4) orbitals of the LUMO. The low energy band of Re(CO)3(pterin)(H2O) can be
      described as a combination of different MLLCT transitions where electron density
      residing on different pi orbitals of carbonyl-Re bonds and lone pairs of Re is
      transferred to pterin moiety. Besides MLLCT transitions, IL, LLCT and LLMCT
      transitions contribute the absorptions of the Re(I) complex in the wavelength
      region corresponding to the high energy bands. The calculated electronic spectra
      of the acid and base forms of pterin and Re(CO)3(pterin)(H2O) were simulated from
      the theoretical results and compared to the experimental absorption spectra with
      great accuracy both in position and relative intensities of the absorption bands.

PMID- 24727178
TI  - Application of thermogravimetry-differential thermal analysis (TG-DTA) technique
      to study the ancient potteries from Vellore dist, Tamilnadu, India.
AB  - The characterization of archeological ceramic and pottery can be studied for the
      determination of firing temperature and the presence of raw materials by thermal
      analysis. Clay minerals are the main material for the production of ceramic and
      pottery and show some characteristic reactions such as dehydration,
      dehydroxylation and transformation. This is key point of criteria for the
      elucidation of firing temperature and raw material analysis. In the present work,
      DTA-TG, XRD and EDXRF technique are applied on representative potsherds from
      Vellore dist., Tamilnadu, India to derive the information about the production
      technology, raw materials and firing temperature. From the analysis, all the
      samples were considered to be fired from 800 degrees C to 900 degrees C and
      organic material might be added intestinally as a binder in the preparation of
      pottery. 

PMID- 24727179
TI  - New way to call time on high strength, cheap alcohol.

PMID- 24727180
TI  - BMJ Awards 2014. Gastroenterology team of the year.

PMID- 24727181
TI  - Woman challenges NHS refusal to fund egg freezing before treatment that may make
      her infertile.

PMID- 24727182
TI  - Inducing hypothermia after out of hospital cardiac arrest.

PMID- 24727183
TI  - Antiparasitic activities of novel ruthenium/lapachol complexes.
AB  - The present study describes the synthesis, characterization, antileishmanial and
      antiplasmodial activities of novel diimine/(2,2'-bipyridine (bipy), 1,10
      phenanthroline (phen), 4,4'-methylbipyridine (Me-bipy) and 4,4'-methoxybipyridine
      (MeO-bipy)/phosphine/ruthenium(II) complexes containing lapachol (Lap, 2-hydroxy
      3-(3-33 methyl-2-buthenyl)-1,4-naphthoquinone) as bidentate ligand. The
      [Ru(Lap)(PPh3)2(bipy)]PF6 (1), [Ru(Lap)(PPh3)2(Me-bipy)]PF6 (2),
      [Ru(Lap)(PPh3)2(MeO-bipy)]PF6(3) and[Ru(Lap)(PPh3)2(phen)]PF6 (4) complexes,
      PPh3=triphenylphospine, were synthesized from the reactions of cis
      [RuCl2(PPh3)2(X-bipy)] or cis-[RuCl2(PPh3)2(phen)], with lapachol. The
      [RuCl2(Lap)(dppb)] (5) [dppb=1,4-bis(diphenylphosphine)butane] was synthesized
      from the mer-[RuCl3(dppb)(H2O)] complex. The complexes were characterized by
      elemental analysis, molar conductivity, infrared and UV-vis spectroscopy,
      (31)P{(1)H} and (1)H NMR, and cyclic voltammetry. The Ru(III) complex,
      [RuCl2(Lap)(dppb)], was also characterized by the EPR technique. The structure of
      the complexes [Ru(Lap)(PPh3)2(bipy)]PF6 and [RuCl2(Lap)(dppb)] was elucidated by
      X-ray diffraction. The evaluation of the antiparasitic activities of the
      complexes against Leishmania amazonensis and Plasmodium falciparum demonstrated
      that lapachol-ruthenium complexes are more potent than the free lapachol. The
      [RuCl2(Lap)(dppb)] complex is the most potent and selective antiparasitic
      compound among the five new ruthenium complexes studied in this work, exhibiting
      an activity comparable to the reference drugs. 

PMID- 24727184
TI  - The ARUBA study: what is the evidence?

PMID- 24727185
TI  - Impact of visitors and hospital staff on nosocomial transmission and spread to
      community.
AB  - We develop a deterministic meta-population model to qualitatively capture some
      key features of disease transmission between a community and its healthcare
      facility. We consider the disease transmission dynamics within a healthcare
      facility and between the healthcare facility and its community. The focus of this
      study is to quantify the roles of the healthcare workers at and visitors to this
      healthcare facility in shaping the transmission dynamics during a disease
      outbreak. We stratify the total population into the general population in the
      community and the healthcare workers and visitors in the healthcare facility, to
      account for nosocomial transmission in the case when an individual in the
      community may be exposed to an infection due to a visit to the healthcare
      facility. Equilibrium stability analysis is carried out to inform long-term
      outcomes of disease dynamics in the coupled community-health care facility
      system. The basic reproduction number is calculated and its dependence on the
      waiting time and various disease transmission rates is analyzed. Numerical
      simulations are performed with pertussis as the disease in question. The results
      show that waiting time only affects the peak number of infections in the waiting
      reception area. The results also indicate that transmission rate of infective
      residents in the community and the transmission rate of the infective visitors at
      the healthcare facility have decisive impact on disease eradication/persistence
      of the coupled system; while other modes of transmissions are less important,
      affecting the peak number of infections at best. 

PMID- 24727186
TI  - Coaction versus reciprocity in continuous-time models of cooperation.
AB  - Cooperating animals frequently show closely coordinated behaviours organized by a
      continuous flow of information between interacting partners. Such real-time
      coaction is not captured by the iterated prisoner's dilemma and other discrete
      time reciprocal cooperation games, which inherently feature a delay in
      information exchange. Here, we study the evolution of cooperation when
      individuals can dynamically respond to each other's actions. We develop
      continuous-time analogues of iterated-game models and describe their dynamics in
      terms of two variables, the propensity of individuals to initiate cooperation
      (altruism) and their tendency to mirror their partner's actions (coordination).
      These components of cooperation stabilize at an evolutionary equilibrium or show
      oscillations, depending on the chosen payoff parameters. Unlike reciprocal
      altruism, cooperation by coaction does not require that those willing to initiate
      cooperation pay in advance for uncertain future benefits. Correspondingly, we
      show that introducing a delay to information transfer between players is
      equivalent to increasing the cost of cooperation. Cooperative coaction can
      therefore evolve much more easily than reciprocal cooperation. When delays
      entirely prevent coordination, we recover results from the discrete-time
      alternating prisoner's dilemma, indicating that coaction and reciprocity are
      connected by a continuum of opportunities for real-time information exchange.

PMID- 24727188
TI  - Eco-hydrology driven fire regime in savanna.
AB  - Fire is an important evolutionary force and ecosystem consumer that shapes
      savanna composition. However, ecologists have not comprehensively explained the
      functioning and maintenance of flammable savannas. A new minimal model accounting
      for the interdependence between soil saturation, biomass growth, fuel
      availability and fire has been used to predict the increasing tree density and
      fire frequency along a Mean Annual Rainfall (MAR) gradient for a typical savanna.
      Cyclic fire recurrence is reproduced using a predator prey approach in which fire
      is the "predator" and vegetation is the "prey". For the first time, fire
      frequency is not defined a priori but rather arises from the composition of
      vegetation, which determines fuel availability and water limitation. Soil aridity
      affects fuel production and fuel composition, thus indirectly affecting the
      ecosystem vulnerability to fire and fire frequency. The model demonstrates that
      two distinct eco-hydrological states correspond to different fire frequencies:
      (i) at low MAR, grass is abundant and the impact of fire on the environment is
      enhanced by the large fuel availability, (ii) at higher MAR, tree density
      progressively increases and provides less fuel for fire, leading to more frequent
      and less destructive fires, and (iii) the threshold MAR that determines the
      transition between the two states and the fire frequency at high MAR are affected
      by the vulnerability of trees to grass fire. The eco-hydrology-driven predator
      prey model originally predicts that the transition between dry and wet savanna is
      characterized by a shift in wildfire frequency driven by major differences in
      soil moisture available for plants and savanna structure. The shift and the role
      of fire in conserving savanna ecosystems could not have been predicted if fire
      was considered as an external forcing rather than an intrinsic property of the
      ecosystem. 

PMID- 24727187
TI  - Who mixes with whom among men who have sex with men? Implications for modelling
      the HIV epidemic in southern India.
AB  - In India, the identity of men who have sex with men (MSM) is closely related to
      the role taken in anal sex (insertive, receptive or both), but little is known
      about sexual mixing between identity groups. Both role segregation (taking only
      the insertive or receptive role) and the extent of assortative (within-group)
      mixing are known to affect HIV epidemic size in other settings and populations.
      This study explores how different possible mixing scenarios, consistent with
      behavioural data collected in Bangalore, south India, affect both the HIV
      epidemic, and the impact of a targeted intervention. Deterministic models
      describing HIV transmission between three MSM identity groups (mostly insertive
      Panthis/Bisexuals, mostly receptive Kothis/Hijras and versatile Double Deckers),
      were parameterised with behavioural data from Bangalore. We extended previous
      models of MSM role segregation to allow each of the identity groups to have both
      insertive and receptive acts, in differing ratios, in line with field data. The
      models were used to explore four different mixing scenarios ranging from
      assortative (maximising within-group mixing) to disassortative (minimising within
      group mixing). A simple model was used to obtain insights into the relationship
      between the degree of within-group mixing, R0 and equilibrium HIV prevalence
      under different mixing scenarios. A more complex, extended version of the model
      was used to compare the predicted HIV prevalence trends and impact of an HIV
      intervention when fitted to data from Bangalore. With the simple model, mixing
      scenarios with increased amounts of assortative (within-group) mixing tended to
      give rise to a higher R0 and increased the likelihood that an epidemic would
      occur. When the complex model was fit to HIV prevalence data, large differences
      in the level of assortative mixing were seen between the fits identified using
      different mixing scenarios, but little difference was projected in future HIV
      prevalence trends. An oral pre-exposure prophylaxis (PrEP) intervention was
      modelled, targeted at the different identity groups. For intervention strategies
      targeting the receptive or receptive and versatile MSM together, the overall
      impact was very similar for different mixing patterns. However, for PrEP
      scenarios targeting insertive or versatile MSM alone, the overall impact varied
      considerably for different mixing scenarios; more impact was achieved with
      greater levels of disassortative mixing. 

PMID- 24727189
TI  - A novel biophysical model on calcium and voltage dual dependent gating of calcium
      activated chloride channel.
AB  - Ca(2+)-activated Cl(-) channels (CaCCs) are anion-selective channels and involved
      in physiological processes such as electrolyte/fluid secretion, smooth muscle
      excitability, and olfactory perception which critically depend on the Ca(2+) and
      voltage dual-dependent gating of channels. However, how the Ca(2+) and voltage
      regulate the gating of CaCCs still unclear. In this work, the authors constructed
      a biophysical model to illustrate the dual-dependent gating of CaCCs. For
      validation, we applied our model on both native CaCCs and exogenous TMEM16A which
      is thought to be the molecular basis of CaCCs. Our data show that the native
      CaCCs may share universal gating mechanism. We confirmed the assumption that by
      binding with the channel, Ca(2+) decreases the energy-barrier to open the
      channel, but not changes the voltage-sensitivity. For TMEM16A, our model
      indicates that the exogenous channels show different Ca(2+) dependent gating
      mechanism from the native ones. These results advance the understanding of
      intracellular Ca(2+) and membrane potential regulation in CaCCs, and shed new
      light on its function in aspect of physiology and pharmacology. 

PMID- 24727190
TI  - Anti-inflammatory effects of Bryophyllum pinnatum (Lam.) Oken ethanol extract in
      acute and chronic cutaneous inflammation.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Bryophyllum pinnatum (Lam.) Oken (Crassulaceae),
      popularly known in Brazil as "folha-da-fortuna", is a plant species used in folk
      medicine for the external and internal treatment of inflammation, infection,
      wound, burn, boil, ulcers and gastritis, and several other diseases. The present
      study aimed to perform the chemical characterization and the evaluation of the
      topical anti-inflammatory effect of the ethanol extract of Bryophyllum pinnatum
      leaves (EEBP) in acute and chronic mice ear edema models induced by different
      irritant agents. MATERIALS AND METHODS: The EEBP chemical characterization was
      performed by HPLC-UV DAD. Ear edema on Swiss mice was induced by the topical
      application of Croton oil (single and multiple applications), arachidonic acid,
      phenol, capsaicin and ethyl phenylpropiolate (EPP). The topical anti-inflammatory
      effect of EEBP was evaluated by measuring the ear weight (acute inflammation
      models) and thickness (chronic inflammation model). Histopathological analyses of
      ear tissue samples sensitized with Croton oil (single and multiple applications)
      were also performed. RESULTS: The flavonoids rutin, quercetin, luteolin and
      luteolin7-O-beta-d-glucoside were detected in EEBP. Topical application of EEBP
      significantly (P<0.001) inhibited the ear edema induced by Croton oil single
      application (inhibition of 57%), arachidonic acid (inhibition of 67%), phenol
      (inhibition of 80%), capsaicin (inhibition of 72%), EPP (inhibition of 75%) and
      Croton oil multiple application (55% after 9 days). Histopathological analyses
      confirmed the topical anti-inflammatory effect of EEBP since it was observed
      reduction of edema, epidermal hyperplasia, inflammatory cells infiltration and
      vasodilation. CONCLUSIONS: The results suggest that EEBP is effective as a
      topical anti-inflammatory agent in acute and chronic inflammatory processes
      possibly due to inhibition of arachidonic acid pathway, which justify the
      traditional use of Bryophyllum pinnatum as a remedy for skin disorders.

PMID- 24727191
TI  - Therapeutic effect of Soshiho-tang, a traditional herbal formula, on liver
      fibrosis or cirrhosis in animal models: a systematic review and meta-analysis.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Liver fibrosis has been recognized as a major
      lesion of the liver that leads to liver cirrhosis at the end stage. Soshiho-tang
      (SST) has been used to improve liver fibrosis/cirrhosis by ameliorating fibrosis
      specific markers. This study aimed to assess the efficacy of SST on liver
      fibrosis/cirrhosis through a systematic review of the literature and meta
      analysis using animal models. MATERIALS AND METHODS: Studies of SST treatment in
      liver fibrosis/cirrhosis-induced animal models were searched by electronic data
      bases. The quality of the studies included was assessed and the efficacy of SST
      was evaluated based on markers from liver tissues and serum. RESULTS: Among the
      838 studies identified in the literature search, 20 studies that met the
      inclusion criteria were included in the analysis. SST significantly reduced the
      elevated levels of fibrosis markers, such as the degree of fibrosis,
      hydroxyproline, hyaluronic acid, transforming growth factor-beta1, and
      procollagen III in liver tissues, and aspartate aminotransferase, alanine
      aminotransferase, procollagen III, tissue inhibitor of metalloproteinase-1, and
      type IV collagen in the serum. CONCLUSIONS: SST was effective in decreasing
      pathologically increased markers in animal models of liver fibrosis/cirrhosis. A
      larger-scale of animals, well-designed animal study is expected to improve the
      methodological quality, heterogeneity, and potential biases of the meta-analysis.

PMID- 24727192
TI  - Gochnatia polymorpha ssp. floccosa: bioprospecting of an anti-inflammatory
      phytotherapy for use during pregnancy.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Gochnatia polymorpha ssp. floccosa is used in
      folk medicine to treat inflammation and infections. Non-steroidal anti
      inflammatory drugs (NSAIDs) are the most commonly consumed medications during
      pregnancy in women with inflammatory diseases. However, the relationship between
      the use of NSAIDs and the risk of miscarriage and birth defects and/or benefits
      is not fully understood. Thus, an investigation regarding the use of Gochnatia
      polymorpha during gestation is of relevance for developing safe anti-inflammatory
      drugs for use during pregnancy. MATERIALS AND METHODS: The pregnant females were
      randomly divided into 5 groups. Control group received a hydroalcoholic solution
      (1.2%), via gavage, for at least 15 days prior to mating and throughout the
      gestational period. The pre-treatment group received Gochnatia polymorpha ethanol
      extract (GPEE), via gavage, at a dose of 100mg/kg body weight (b.w.) for at least
      15 days prior to mating and up to the appearance of the vaginal plug. The
      organogenesis group received GPEE at a dose of 100mg/kg (b.w.), via gavage, on
      the 5-15th gestacional day. The pregnancy group received GPEE at a dose of
      100mg/kg (b.w.), via gavage, throughout the gestational period (from the 1st to
      the 18th day of pregnancy). The pre+pregnancy group received GPEE at a dose of
      100mg/kg (b.w.), via gavage, for at least 15 days prior to mating and throughout
      the entire gestational period. The clinical signals of maternal toxicity and
      teratogenesis were evaluated. Additional assays to evaluate chronic inflammation,
      antigenotoxicity and immunomodolatory activity were performed. RESULTS AND
      CONCLUSIONS: The results indicated that GPEE does not interfere with reproductive
      performance or embryo-fetal development but does correlate with reduced weight
      and fetal length. The extract was not teratogenic or mutagenic or an
      immunomodulator. However, GPEE did exhibit effective anti-inflammatory activity.
      Based on this study, it can be inferred that GPEE is an important, safe anti
      inflammatory agent for use during pregnancy according to the experimental design
      we utilized, which opens up possibilities for the bioprospecting of a new anti
      inflammatory phytotherapy for use during pregnancy.

PMID- 24727193
TI  - Effect of low levels of Bacillus thuringiensis exposure on the growth, food
      consumption and digestion efficiencies of Trichoplusia ni resistant and
      susceptible to Bt.
AB  - It is becoming increasingly clear that the impact of low doses of an
      environmental stressor, such as Bacillus thuringiensis, can often not be
      predicted from high dose experiments, and the impact of these effects on the
      evolution of resistance has received little attention. In the present study, we
      examined the effect of low levels of B. thuringiensis exposure on the growth,
      food consumption and digestion efficiencies of Trichoplusia ni resistant and
      susceptible to Bt. Larvae were fed on specified Bt concentrations continually for
      3 days. Resistant larvae exhibited increases in diet consumption, weight gain and
      conversion of ingested food to biomass in response to feeding continually on some
      of the Bt concentrations. The positive effect of feeding on low levels of Bt on
      the growth of resistant larvae was modulated by initial larval size and the
      amount of food consumed. In contrast, susceptible larvae exhibited reductions in
      growth and frass production at all tested Bt concentrations. Further studies are
      needed to determine the role of accelerated growth on the evolution of Bt
      resistance in T. ni populations and to evaluate the importance of life-history
      responses to sublethal concentrations in the context of insecticide resistance
      management.

PMID- 24727194
TI  - Recovery in psychosis: a Delphi study with experts by experience.
AB  - This study aimed to establish consensus about the meaning of recovery among
      individuals with experience of psychosis. A Delphi approach was utilized to allow
      a large sample of service users to be anonymously consulted about their views on
      recovery. Service users were invited to take part in a 3-stage consultation
      process. A total of 381 participants gave their views on recovery in the main
      stage of this study, with 100 of these taking part in the final review stage. The
      final list of statements about recovery included 94 items, which were rated as
      essential or important by >80% of respondents. These statements covered items
      which define recovery, factors which help recovery, factors which hinder
      recovery, and factors which show that someone is recovering. As far as we are
      aware, it is the first study to identify areas of consensus in relation to
      definitions of recovery from a service user perspective, which are typically
      reported to be an idiosyncratic process. Implications and recommendations for
      clinical practice and future research are discussed. 

PMID- 24727195
TI  - Complementary roles of benzylpiperazine and iodine 'vapor' in the strong
      enhancement of orange photoluminescence from CuI(1 1 1) thin film.
AB  - We have employed density functional theory, corrected by the on-site electron
      electron repulsion energy U, to clarify the mechanism behind the enhanced orange
      photoluminescence (PL) of a CuI(1 1 1) thin film conjugated with a
      benzylpiperazine (BZP) molecule in the presence of an iodine 'vapor' atom. Our
      results demonstrated that the adsorbed molecule and the 'vapor' atom play
      complementary roles in producing the PL. The latter, in attaching to the film
      surface, creates a hole-trapping surface state located ~0.25 eV above the valence
      band-edge of the film, in good agreement with ~0.2 eV reported in experiments.
      Upon photo-excitation of the BZP/CuI(1 1 1) system in the presence of surface
      iodine 'vapor' atoms, excited electrons are transferred into the conduction band
      of CuI, and holes are trapped by the 'vapor' atoms. These holes, in turn, quickly
      relax into the HOMO state of the BZP molecule, owing to the fact that the
      molecule adsorbs on the film surface in the immediate vicinity of a 'vapor' atom.
      Relaxed holes subsequently recombine with excited electrons in the conduction
      band of the CuI film, thereby producing a luminescence peak at ~2.1 eV, in
      qualitative agreement with experimental findings.

PMID- 24727196
TI  - Function of shrimp STAT during WSSV infection.
AB  - JAK/STAT signaling pathway plays key roles in the antiviral immunity of mammals,
      fish and insect. However, limited knowledge is known about the function of
      JAK/STAT signaling pathway in the antiviral immunity of shrimp although virus
      disease has caused severe mortality in shrimp aquaculture. In order to understand
      the function of JAK/STAT signaling pathway in the antiviral immunity of shrimp,
      dsRNA interfering technique was used to silence the expression of STAT gene in
      Litopenaeus vannamei, and the mortality of shrimp was detected after WSSV
      infection. Furthermore, the expressions of some potential target genes regulated
      by STAT or genes related to RNA interfering pathway were detected in STAT
      silenced shrimp during WSSV infection. The WSSV copy number in STAT silenced
      shrimp was 10(2)-10(3) copies/ng DNA which was much lower than that in the
      control. The mortality in STAT silenced shrimp caused by WSSV infection decreased
      very significantly compared to their controls. The function of STAT was verified
      in vitro cultured cells of hematopoietic tissue of crayfish Cherax
      quadricarinatus by adding specific inhibitor of STAT3(S3I-201), and the cultured
      cells treated with S3I-201 showed much less WSSV copy number than their controls,
      which further suggested that STAT might be helpful for the replication of WSSV.
      Expression analysis on the potential STAT target genes and genes in RNA
      interfering pathway provide important information for understanding the
      functional mechanism of STAT in antiviral immunity of shrimp. 

PMID- 24727197
TI  - Molecular characterization and functional analysis of two distinct liver
      expressed antimicrobial peptide 2 (LEAP-2) genes in large yellow croaker
      (Larimichthys crocea).
AB  - Liver-expressed antimicrobial peptide 2 (LEAP-2) plays a vital role in the host
      innate immune system. In the present study, two LEAP-2 genes (LcLEAP-2A and
      LcLEAP-2C) from large yellow croaker (Larimichthys crocea) were cloned, both of
      which consist of 3 exons and 2 introns. The LcLEAP-2A transcripts were expressed
      in a wide range of tissues, with the highest mRNA levels found in the liver and
      intestine, while LcLEAP-2C transcripts showed obvious lower mRNA levels in all
      tested tissues compared to LcLEAP-2A. Upon infection by Vibrio alginolyticus,
      LcLEAP-2A transcripts were significantly up-regulated in liver, trunk kidney,
      spleen, head kidney, and gill, but down-regulated in intestine. In addition,
      significant up-regulation of LcLEAP-2C transcripts were also detected in all
      tissues tested, including intestine. The LcLEAP-2A and LcLEAP-2C mature peptides
      were chemically synthesized and found to exhibit selective antimicrobial activity
      in vitro against various species of bacteria. LcLEAP-2C, but not LcLEAP-2A, had
      antimicrobial activity against V. alginolyticus. Moreover, LcLEAP-2C treatment at
      low concentrations was evaluated and found to improve survival rate in V.
      alginolyticus-infected large yellow croaker, resulting in a decrease in bacterial
      load and expression of inflammatory cytokines. These results suggest that LcLEAP
      2 isoforms play an important role in innate immunity by killing bacteria and
      inhibiting early inflammatory response in large yellow croaker. 

PMID- 24727198
TI  - Effect of intestinal autochthonous probiotics isolated from the gut of sea
      cucumber (Apostichopus japonicus) on immune response and growth of A. japonicus.
AB  - The study isolated 224 bacteria from the intestine of Apostichopus japonicus,
      then selected and identified three of the bacteria (HS1, HS7, and HS10) which
      demonstrated amylase, lipase, and protease production capacity as candidate
      probiotics for sea cucumbers. The three potential probiotics showed no
      pathogenicity both in hemolytic assays on sheep blood agar plates and after
      immersing sea cucumbers in a suspension of the bacteria. To reveal the effects of
      these three potential probiotics on the innate immunity of sea cucumbers, total
      coelomocyte counts, respiratory burst activity, superoxide dismutase activity,
      lysozyme activity, acid phosphatase activity, and phagocytic activity by
      coelomocytes were examined after feeding with four different diets for up to 28
      days. Also the specific growth rate and survival rate were investigated after a
      60-day feeding trial. Sea cucumbers were fed with 4 diets: one control, three
      diets supplemented with 1 * 10(9) cell g(-1) of HS1, HS7, and HS10 for 28-60
      days. Results showed that sea cucumbers fed diets containing HS1, HS7, and HS10
      had led to an enhanced cellular and humoral immune response, notably higher total
      coelomocytes counts, respiratory burst activity, lysozyme activity, acid
      phosphatase activity, and phagocytic activity, as recorded during the four weeks
      of probiotics administration. On the other hand, the survival rate among dietary
      treatments ranged from 90.71 to 97.97% with significant improvement (P < 0.05)
      compared to that of the control; and the growth rate observed in the sea
      cucumbers fed HS1 and HS7 showed sharp increases after 60 days feeding. The
      present study confirmed the potential beneficial effects of Pseudoalteromonas
      elyakovii HS1, Shewanella japonica HS7, and Vibrio tasmaniensis HS10 as dietary
      probiotics in A. japonicus. 

PMID- 24727199
TI  - Evolution of the viral hemorrhagic septicemia virus: divergence, selection and
      origin.
AB  - Viral hemorrhagic septicemia virus (VHSV) is an economically significant
      rhabdovirus that affects an increasing number of freshwater and marine fish
      species. Extensive studies have been conducted on the molecular epizootiology,
      genetic diversity, and phylogeny of VHSV. However, there are discrepancies
      between the reported estimates of the nucleotide substitution rate for the G gene
      and the divergence times for the genotypes. Herein, Bayesian coalescent analyses
      were conducted to the time-stamped entire coding sequences of the six VHSV genes.
      Rate estimates based on the G gene indicated that the marine genotypes/subtypes
      might not all evolve slower than their major European freshwater counterpart. Age
      calculations on the six genes revealed that the first bifurcation event of the
      analyzed isolates might have taken place within the last 300 years, which was
      much younger than previously thought. Selection analyses suggested that two
      codons of the G gene might be positively selected. Surveys of codon usage bias
      showed that the P, M and NV genes exhibited genotype-specific variations.
      Furthermore, we proposed that VHSV originated from the Pacific Northwest of North
      America.

PMID- 24727200
TI  - Effective stiffness of qPlus sensor and quartz tuning fork.
AB  - Quartz tuning forks (QTFs) have been extensively employed in scanning probe
      microscopy. For quantitative measurement of the interaction in nanoscale using
      QTF as a force sensor, we first measured the effective stiffness of qPlus sensors
      as well as QTFs and then compared the results with the cantilever beam theory
      that has been widely used to estimate the stiffness. Comparing with the stiffness
      and the resonance frequency in our measurement, we found that those calculated
      based on the beam theory are considerably overestimated. For consistent analysis
      of experimental and theoretical results, we present the formula to calculate the
      stiffness of qPlus sensor or QTF, based on the resonance frequency. We also
      demonstrated that the effective stiffness of QTF is twice that of qPlus sensor,
      which agrees with the recently suggested model. Our study demonstrates the use of
      QTF for quantitative measurement of interaction force at the nanoscale in
      scanning probe microscopy. 

PMID- 24727201
TI  - Planar Hall magnetoresistive aptasensor for thrombin detection.
AB  - The use of aptamer-based assays is an emerging and attractive approach in disease
      research and clinical diagnostics. A sensitive aptamer-based sandwich-type sensor
      is presented to detect human thrombin using a planar Hall magnetoresistive (PHR)
      sensor in cooperation with superparamagnetic labels. A PHR sensor has the great
      advantages of a high signal-to-noise ratio, a small offset voltage and linear
      response in the low-field region, allowing it to act as a high-resolution
      biosensor. In the system presented here, the sensor has an active area of 50 um *
      50 um with a 10-nm gold layer deposited onto the sensor surface prior to the
      binding of thiolated DNA primary aptamer. A polydimethylsiloxane well of 600-um
      radius and 1-mm height was prepared around the sensor surface to maintain the
      same specific area and volume for each sensor. The sensor response was traced in
      real time upon the addition of streptavidin-functionalized magnetic labels on the
      sensor. A linear response to the thrombin concentration in the range of 86 pM-8.6
      uM and a lower detection limit down to 86 pM was achieved by the proposed present
      method with a sample volume consumption of 2 ul. The proposed aptasensor has a
      strong potential for application in clinical diagnosis.

PMID- 24727202
TI  - An efficient biosensor made of an electromagnetic trap and a magneto-resistive
      sensor.
AB  - Magneto-resistive biosensors have been found to be useful because of their high
      sensitivity, low cost, small size, and direct electrical output. They use super
      paramagnetic beads to label a biological target and detect it via sensing the
      stray field. In this paper, we report a new setup for magnetic biosensors,
      replacing the conventional "sandwich" concept with an electromagnetic trap. We
      demonstrate the capability of the biosensor in the detection of E. coli. The trap
      is formed by a current-carrying microwire that attracts the magnetic beads into a
      sensing space on top of a tunnel magneto-resistive sensor. The sensor signal
      depends on the number of beads in the sensing space, which depends on the size of
      the beads. This enables the detection of biological targets, because such targets
      increase the volume of the beads. Experiments were carried out with a 6 um wide
      microwire, which attracted the magnetic beads from a distance of 60 MUm, when a
      current of 30 mA was applied. A sensing space of 30 um in length and 6 um in
      width was defined by the magnetic sensor. The results showed that individual E.
      coli bacterium inside the sensing space could be detected using super
      paramagnetic beads that are 2.8 um in diameter. The electromagnetic trap setup
      greatly simplifies the device and reduces the detection process to two steps: (i)
      mixing the bacteria with magnetic beads and (ii) applying the sample solution to
      the sensor for measurement, which can be accomplished within about 30 min with a
      sample volume in the ul range. This setup also ensures that the biosensor can be
      cleaned easily and re-used immediately. The presented setup is readily integrated
      on chips via standard microfabrication techniques.

PMID- 24727203
TI  - Missense variants of the alanine:glyoxylate aminotransferase 2 gene are not
      associated with Japanese schizophrenia patients.
AB  - Alanine:glyoxylate aminotransferase 2 (AGXT2) is the only enzyme that degrades D
      3-aminoisobutyrate (D-AIB), which is an intermediate product of thymine, and 30
      40% of Japanese lack AGXT2 activity genetically and excrete high amounts of D-AIB
      in their urine. Recently, AGXT2 is reported to metabolize asymmetric dimethyl
      arginine (ADMA), a competitive inhibitor of nitric oxide (NO) synthase. Since
      AGXT2 is expressed in the central nervous system, the loss of AGXT2 activity will
      be related to the vulnerability for neuropsychiatric disorders related to the NO
      system. In this study, we recruited 85 Japanese subjects to discover loss
      variants of the AGXT2 gene with the amount of D-AIB excretion in their urine.
      From the statistical relevance between them, we found three missense
      polymorphisms (rs37370, rs37369, and rs180749) independently related to AGXT2
      activity (P<0.0001). Then, we performed a case-control association analysis of
      its missense polymorphisms with 1136 schizophrenia and 1908 control subjects
      because the NO system may be involved in the vulnerability of schizophrenia
      processes. We could not find any associations of three functional SNPs with
      schizophrenia pathogenesis in the analyses of either genotypic or allelic models.
      We concluded that the AGXT2 gene is not associated with schizophrenia in Japanese
      subjects. 

PMID- 24727204
TI  - Methodology to develop crash modification functions for road safety treatments
      with fully specified and hierarchical models.
AB  - Crash modification factors (CMFs) for road safety treatments are developed as
      multiplicative factors that are used to reflect the expected changes in safety
      performance associated with changes in highway design and/or the traffic control
      features. However, current CMFs have methodological drawbacks. For example,
      variability with application circumstance is not well understood, and, as
      important, correlation is not addressed when several CMFs are applied
      multiplicatively. These issues can be addressed by developing safety performance
      functions (SPFs) with components of crash modification functions (CM-Functions),
      an approach that includes all CMF related variables, along with others, while
      capturing quantitative and other effects of factors and accounting for cross
      factor correlations. CM-Functions can capture the safety impact of factors
      through a continuous and quantitative approach, avoiding the problematic
      categorical analysis that is often used to capture CMF variability. There are two
      formulations to develop such SPFs with CM-Function components - fully specified
      models and hierarchical models. Based on sample datasets from two Canadian
      cities, both approaches are investigated in this paper. While both model
      formulations yielded promising results and reasonable CM-Functions, the
      hierarchical model was found to be more suitable in retaining homogeneity of
      first-level SPFs, while addressing CM-Functions in sub-level modeling. In
      addition, hierarchical models better capture the correlations between different
      impact factors. 

PMID- 24727205
TI  - The prevalence of malnutrition and fat-soluble vitamin deficiencies in chronic
      pancreatitis.
AB  - BACKGROUND: Patients with chronic pancreatitis are at risk of malnutrition and
      nutrient deficiency due to malabsorption, pain, and poor diet. We sought to
      examine fat-soluble vitamin levels and malnutrition parameters in patients with
      chronic pancreatitis. MATERIALS AND METHODS: In a prospective controlled cohort
      study, 128 subjects (62 chronic pancreatitis patients and 66 age-/sex-matched
      controls) were recruited. Body mass index (BMI), handgrip strength (measure of
      functional capacity), fat stores (triceps skin fold), muscle stores (mid-arm
      muscle circumference), exocrine function, and serum levels of fat-soluble
      vitamins (A, D, E) were measured. RESULTS: Half of patients in the chronic
      pancreatitis group were overweight or obese, although the mean BMI was lower in
      patients than in controls (P = .007). Handgrip strength (P = .048), fat stores (P
      = .000), and muscle stores (P = .001) were lower in patients than in controls. Of
      the patients, 14.5% and 24.2% were deficient in vitamins A and E, respectively.
      Nineteen percent of patients had excess serum vitamin A levels. CONCLUSIONS:
      Despite the prevalence of overweight and obesity, patients had lower muscle
      stores, strength, and abnormal vitamin levels. Detailed nutrition assessment
      including anthropometry and vitamin status is warranted in chronic pancreatitis.

PMID- 24727206
TI  - Use of wing morphometrics to identify populations of the Old World screwworm fly,
      Chrysomya bezziana (Diptera: Calliphoridae): a preliminary study of the utility
      of museum specimens.
AB  - The Old World screwworm (OWS) fly, Chrysomya bezziana (Diptera: Calliphoridae),
      is a major economic and welfare problem for humans and animals in the Old World
      tropics. Using a bootstrapped log likelihood ratio test of the output of
      Procrustes principal components and canonical variates analyses for a small
      sample of museum specimens from which 19 2D wing landmarks had been collected:
      (1) a consistent and statistically significant difference exists between landmark
      configurations derived from wings of pinned specimens and those removed from the
      body and mounted on slides; (2) a highly statistically significant sexual
      dimorphism in wing morphometry was identified; and (3) a highly statistically
      significant difference in wing morphometry between populations of the OWS fly
      from Africa (Tanzania, South Africa Sudan, Zaire, Zimbabwe,) and Asia (Sumba,
      Indonesia) exists. These results show that wing orientation and gender must be
      considered when conducting morphometric investigations of OWS fly wings. The
      latter result is also consistent with results from previous molecular and
      morphological studies, which indicate there are two distinct genetic lineages
      within this species. Wing morphometry holds great promise as a practical tool to
      aid in identification of the geographical origin of introductions of this
      important pest species, by providing diagnostic markers to distinguish
      geographical populations and complement molecular diagnostics. 

PMID- 24727207
TI  - Intussusception secondary to a carcinoid tumor in an adult patient.
AB  - INTRODUCTION: Intussusception in adult patients represents 5% of all
      intussusceptions and 1-5% of bowel obstructions in adults. In contrast to
      pediatric patients, 90% of the time, in adults, it's caused by well-established
      pathologic mechanisms, such as carcinoma, polyps, diverticula, Meckel
      diverticula, stenosis, or benign neoplasms. Small intestine intussusceptions are
      more frequent, but colonic intussusceptions are caused 50% of the time by
      malignant neoplasms, especially adenocarcinoma. PRESENTATION OF CASE: We present
      a 70-year-old woman, with no relevant familial history, who presented with a 3
      day symptomatology consisting of epigastric, colic, diffuse, abdominal pain of
      moderate intensity, which progressed till reaching a severe intensity, also
      referring abdominal distension, nausea, and gastrointestinal-content vomits.
      DISCUSSION: In adult patients, the exact mechanism of intussusception is unknown
      in 8-20% of the cases, however, secondary intussusception can occur with any
      lesion of the intestinal wall or any irritant factor in its lumen that alters
      normal peristaltic activity and that could serve as a trigger to start an
      intussusception of one bowel segment over another the most common site is the
      small intestine. CONCLUSION: Intussusception represents an unusual problem in
      adult patients; it requires a high clinical suspicion, mainly as a differential
      diagnosis in patients with intestinal obstruction, and it clinically presents as
      a subacute or chronic illness. CT represents the most useful diagnostic tool. An
      attempt to perform reduction procedures in small intestine intussusceptions can
      be done, however, in ileocolic or colonic intussusceptions, a formal resection of
      the segment is recommended.

PMID- 24727208
TI  - Adenomatoid hyperplasia of the minor salivary glands on the buccal mucosa: A rare
      case report.
AB  - INTRODUCTION: Adenomatoid hyperplasia of the minor salivary glands is a
      hyperplastic oral lesion which may be seen on minor salivary gland bearing areas
      on all oral mucosa, especially on soft and hard palate. This study reports a rare
      case of buccal adenomatoid hyperplasia of the minor salivary glands and discusses
      the clinical significance. PRESENTATION OF CASE: 48 year old male patient
      presented with a complaint of a swelling on his left cheek. Clinical examination
      revealed a bluish mass on the buccal mucosa. A provisional diagnosis of salivary
      gland neoplasm was made and the lesion was excised under local anesthesia. The
      histological diagnosis was adenomatoid hyperplasia of the minor salivary glands.
      DISCUSSION: Buccal localization of the adenomatoid hyperplasia of the minor
      salivary glands is quite uncommon in the literature. There are two cases in the
      English literature for our knowledge. In the clinical examination, the nodular
      and protuberated appearance of the lesion resembles buccal minor salivary gland
      tumors and vascular lesions. Histological analysis is fundamental to achieve
      correct diagnosis. CONCLUSION: The differential diagnosis of buccal nodular,
      exophytic and colored mucosal lesions should include adenomatoid hyperplasia of
      the minor salivary glands.

PMID- 24727209
TI  - Segmental neck of femur fractures: A unique case report of an ipsilateral
      subcapital, greater trochanteric and intertrochanteric fracture and proposed
      management algorithm.
AB  - INTRODUCTION: Neck of femur fractures are now increasingly common in an ageing
      population. The management is well known and has been described in great detail.
      Concomitant ipsilateral segmental fractures of the neck of femur (SFNOF) however
      are rare and their investigation and management is poorly described. PRESENTATION
      OF CASE: We present the surgical management of a unique and complex case of an
      ipsilateral subcapital, greater trochanteric and intertrochanteric fracture
      sustained in an 87-year-old female following a low trauma injury. This fracture
      configuration has not been described in the literature to date, neither has our
      method of reconstruction for this fracture, namely hemiarthorplasty, trochanteric
      stabilising plate and cerclage wires. DISCUSSION: 15 cases from 1989 to 2011
      managed by 8 different fixation devices and followed up for an average of 17
      months (2-58 months). There was an initial mortality rate of 13% (n=2). All
      associated with low energy trauma occurred in female (n=8), and most with high
      energy trauma occurred in males (83%; n=5). The diagnosis was delayed or missed
      in 20% of cases, and the most common pattern was a concomitant undisplaced
      subcapital and intertrochanteric fracture (37.5%, n=6). The overall risk of
      avascular necrosis was 20%, with a greater risk in patients greater than 65 years
      of age (33%). CONCLUSION: Ipsilateral SFNOF are rare injuries with a bimodal
      distribution, and carry a greater risk of AVN. We advise that all SFNOF should
      have pre-operative CT planning and propose an algorithm to treat these patients
      with a standardised surgical approach.

PMID- 24727210
TI  - Psychostimulants, antidepressants and neurokinin-1 receptor antagonists ('motor
      disinhibitors') have overlapping, but distinct, effects on monoamine
      transmission: the involvement of L-type Ca2+ channels and implications for the
      treatment of ADHD.
AB  - Both psychostimulants and antidepressants target monoamine transporters and, as a
      consequence, augment monoamine transmission. These two groups of drugs also
      increase motor activity in preclinical behavioural screens for antidepressants.
      Substance P-preferring receptor (NK1R) antagonists similarly increase both motor
      activity in these tests and monoamine transmission in the brain. In this article,
      the neurochemical and behavioural responses to these three groups of drugs are
      compared. It becomes evident that NK1R antagonists represent a distinct class of
      compounds ('motor disinhibitors') that differ substantially from both
      psychostimulants and antidepressants, especially during states of heightened
      arousal or stress. Also, all three groups of drugs influence the activation of
      voltage-gated Ca(v)1.2 and Ca(v)1.3 L-type channels (LTCCs) in the brain, albeit
      in different ways. This article discusses evidence that points to disruption of
      these functional interactions between NK1R and LTCCs as a contributing factor in
      the cognitive and behavioural abnormalities that are prominent features of
      Attention Deficit Hyperactivity Disorder (ADHD). Arising from this is the
      interesting possibility that the hyperactivity and impulsivity (as in ADHD) and
      psychomotor retardation (as in depression) reflect opposite poles of a
      behavioural continuum. A better understanding of this pharmacological network
      could help explain why psychostimulants augment motor behaviour during stress
      (e.g., in preclinical screens for antidepressants) and yet reduce locomotor
      activity and impulsivity in ADHD. This article is part of the Special Issue
      entitled 'CNS Stimulants'. 

PMID- 24727211
TI  - Reduction of glutamate release probability and the number of releasable vesicles
      are required for suppression of glutamatergic transmission by beta1-adrenoceptors
      in the medial prefrontal cortex.
AB  - The prefrontal cortex (PFC) plays a critical role in cognitive functions,
      including working memory, attention regulation and behavioral inhibition.
      Microinjection of beta1-adrenoceptor (beta1-AR) agonist into the PFC has been
      shown to impair PFC cognitive function. However, the underlying cellular and
      molecular mechanisms have not been determined yet. In the present study, we
      tested the hypothesis that beta1-AR mediated modulation of excitatory synaptic
      transmission contributes to PFC dysfunction. We found that 1) the beta1-AR
      agonist Dobutamine (Dobu) suppressed the amplitude evoked excitatory postsynaptic
      currents (eEPSCs). 2) Dobu induced a significant suppression of the frequency and
      amplitude of miniature EPSCs (mEPSCs). 3) Dobu-suppressed glutamate release was
      mediated via decreasing release probability and the number of releasable
      vesicles. 4) Dobu suppressed inward currents evoked by puff application of
      glutamate or NMDA via postsynaptic PKA-dependent pathway. The present study
      indicates that beta1-AR activation suppresses excitatory synaptic transmission in
      medial PFC (mPFC) via both pre- and post-synaptic PKA-dependent mechanisms. Our
      results may provide a cellular and molecular mechanism that helps explain beta1
      AR-induced PFC dysfunction. 

PMID- 24727212
TI  - A regulatory perspective on the abuse potential evaluation of novel stimulant
      drugs in the United States.
AB  - In the United States of America (USA), the abuse potential assessment of a drug
      is performed as part of the safety evaluation of a drug under development, and to
      evaluate if the drug needs to be subject to controls that would minimize the
      abuse of the drug once on the market. The assessment of the abuse potential of
      new drugs consists of a scientific and medical evaluation of all data related to
      abuse of the drug. This paper describes the regulatory framework for evaluating
      the abuse potential of new drugs, in general, including novel stimulants. The
      role of the United States Food and Drug Administration (FDA) in the evaluation of
      the abuse potential of drugs, and its role in drug control are also discussed. A
      definition of abuse potential, an overview of the currently accepted approaches
      to evaluating the abuse potential of a drug, as well as a description of the
      criteria that applies when recommending a specific level of control (i.e., a
      Schedule) for a drug under the Controlled Substances Act (CSA). This article is
      part of the Special Issue entitled 'CNS Stimulants'. 

PMID- 24727213
TI  - Effects of copper exposure on the energy metabolism in juveniles of the marine
      clam Mesodesma mactroides.
AB  - In freshwater osmoregulating mollusks, Cu can cause toxicity by inducing
      ionoregulatory disturbances. In mussels, it inhibits the activity of key enzymes
      involved in Na(+) uptake and consequently induces ionic and osmotic disturbances.
      In snails, Cu induces disruption of the Ca(2+) homeostasis leading to effects in
      shell deposition and snail growth. However, the mechanisms involved in Cu
      toxicity in osmoconforming sweater mollusks remain unclear. Recent findings from
      our laboratory have suggested that Cu toxicity in marine invertebrates can be
      associated with both ionic and respiratory disturbances. In the present study,
      metabolic changes induced by waterborne Cu exposure were evaluated in the
      osmoconforming clam Mesodesma mactroides, a bivalve species widely distributed
      along the South American sandy beaches. Juvenile clams were kept under control
      conditions (no Cu addition in the water) or acutely (96h) exposed to Cu (96-h
      LC10=150MUgL(-1)) in artificial seawater (30ppt). ATP, protein, lipid, glycogen
      and glucose contents were analyzed in gills, digestive gland, pedal muscle and
      hemolymph. Dinucleotide (NAD(+) and NADH) content was also analyzed in gills,
      digestive gland and pedal muscle while pyruvate and lactate content was
      determined in pedal muscle and hemolymph. In all tissues analyzed, Cu exposure
      did not affect ATP content and NAD(+)/NADH ratio, except in the hemolymph, where
      a decrease in ATP content was observed. These findings indicate that clam cells,
      except those from hemolymph, were able to maintain a constant level of free
      energy. A significant increase in total protein content was observed in the
      digestive gland, which could be a compensatory mechanism to counteract the higher
      level of protein oxidation previously observed in M. mactroides exposed to Cu
      under the same experimental conditions. Finally, reduced glucose content in the
      pedal muscle paralleled by increased lactate content in the pedal muscle and
      hemolymph was observed in Cu-exposed clams. Overall, these findings indicate that
      Cu exposure is leading to an increased reliance upon the anaerobic energy
      production to maintain the overall cellular ATP production in the clam M.
      mactroides. 

PMID- 24727214
TI  - Physiologically-based toxicokinetic models help identifying the key factors
      affecting contaminant uptake during flood events.
AB  - As a consequence of global climate change, we will be likely facing an increasing
      frequency and intensity of flood events. Thus, the ecotoxicological relevance of
      sediment re-suspension is of growing concern. It is vital to understand
      contaminant uptake from suspended sediments and relate it to effects in aquatic
      biota. Here we report on a computational study that utilizes a physiologically
      based toxicokinetic model to predict uptake, metabolism and excretion of sediment
      borne pyrene in rainbow trout (Oncorhynchus mykiss). To this end, data from two
      experimental studies were compared with the model predictions: (a) batch re
      suspension experiments with constant concentration of suspended particulate
      matter at two different temperatures (12 and 24 degrees C), and (b) simulated
      flood events in an annular flume. The model predicted both the final
      concentrations and the kinetics of 1-hydroxypyrene secretion into the gall
      bladder of exposed rainbow trout well. We were able to show that exhaustive
      exercise during exposure in simulated flood events can lead to increased levels
      of biliary metabolites and identified cardiac output and effective respiratory
      volume as the two most important factors for contaminant uptake. The results of
      our study clearly demonstrate the relevance and the necessity to investigate
      uptake of contaminants from suspended sediments under realistic exposure
      scenarios. 

PMID- 24727216
TI  - Bioavailability of the imidazole antifungal agent clotrimazole and its effects on
      key biotransformation genes in the common carp (Cyprinus carpio).
AB  - Clotrimazole (CTZ) is a persistent imidazole antifungal agent which is frequently
      detected in the aquatic environment and predicted to bio-concentrate in fish.
      Common carp (Cyprinus carpio) were exposed to mean measured concentrations of
      either 1.02 or 14.63MUgl(-1) CTZ for 4 and 10 days, followed by a depuration
      period of 4 days in a further group of animals. Following each exposure regimen,
      plasma and liver CTZ concentrations were measured. Mean measured plasma
      concentrations of CTZ in animals exposed to the lower concentration of CTZ were
      30 and 44MUgl(-1) on days 4 and 10, respectively, and in the higher concentration
      were 318 and 336MUgl(-1). Mean measured liver levels in the same animals were
      514, 1725, 2111 and 7017MUgl(-1) suggesting progressive hepatic accumulation.
      Measurement of CTZ in plasma after depuration suggested efficient elimination
      within 4 days, but appreciable levels of CTZ remained in the liver after
      depuration suggesting a degree of persistence in this tissue. In addition we
      measured responses of a number of key hepatic detoxification gene targets in the
      liver associated with the transcription factor pregnane X receptor (PXR); namely
      cyp450s 2k and 3a, glutathione-S-transferases a and p (gsta and p), and drug
      transporters multidrug resistance protein1 (mdr1), and MDR-related protein2
      (mrp2). CTZ is a potent ligand of the PXR in humans and there is some evidence of
      PXR activation following exposure to CTZ in fish. The highest concentration of
      CTZ was adopted to explore the potential for alterations to detoxification gene
      expression in fish at a pharmacologically relevant dose level, and the lower
      concentration is within the range reported in effluents from waste water
      treatment works (WWTW). The genes for all biotransformation enzymes were up
      regulated after exposure to the higher concentration of CTZ for 10 days, and
      alterations in expression occurred for the drug transporter genes mdr1 and mrp2
      following exposure to the lower concentration of 1.02MUgl(-1) CTZ (mean measured
      concentration). These data support the potential for CTZ to induce alterations in
      biotransformation and drug transporter genes associated with PXR in fish at
      concentrations measured in some WWTW effluents. 

PMID- 24727215
TI  - Characterization and transcription studies of a phytochelatin synthase gene from
      the solitary tunicate Ciona intestinalis exposed to cadmium.
AB  - The major thiol-containing molecules involved in controlling the level of
      intracellular ROS in eukaryotes, acting as a nonenzymatic detoxification system,
      are metallothioneins (MTs), glutathione (GSH) and phytochelatins (PCs). Both MTs
      and GSH are well-known in the animal kingdom. PC was considered a prerogative of
      the plant kingdom but, in 2001, a phytochelatin synthase (PCS) gene was described
      in the nematode Caenorhabditis elegans; additional genes encoding this enzyme
      were later described in the earthworm Eisenia fetida and in the parasitic
      nematode Schistosoma mansoni but scanty data are available, up to now, for
      Deuterostomes. Here, we describe the molecular characteristics and transcription
      pattern, in the presence of Cd, of a PCS gene from the invertebrate chordate
      Ciona intestinalis, a ubiquitous solitary tunicate and demonstrate the presence
      of PCs in tissue extracts. We also studied mRNA localization by in situ
      hybridization. In addition, we analyzed the behavior of hemocytes and tunic cells
      consequent to Cd exposure as well as the transcription pattern of the Ciona
      orthologous for proliferating cell nuclear antigen (PCNA), usually considered a
      proliferation marker, and observed that cell proliferation occurs after 96h of Cd
      treatment. This matches the hypothesis of Cd-induced cell proliferation, as
      already suggested by previous data on the expression of a metallothionein gene in
      the same animal. 

PMID- 24727217
TI  - Pharmacological options to protect the aged heart from ischemia and reperfusion
      injury by targeting the PKA-BK(Ca) signaling pathway.
AB  - The beneficial effects of many cardioprotective strategies including ischemic or
      pharmacological conditioning are reduced in the aged heart. The underlying
      reason(s) for the age-dependent loss of cardioprotection is unclear. Recently, we
      demonstrated that protein kinase A (PKA) dependent cardioprotection is lost in
      the aged heart. However, activation of large-conductance Ca(2+)-sensitive K(+)
      (BK(Ca)) channels, a putative PKA downstream target, initiated cardioprotection
      also in the aged heart. Therefore, we aimed to investigate whether 1) BK(Ca)
      channels are critically involved in PKA activation induced cardioprotection and
      2) the age-dependent loss of cardioprotection is caused by differences in PKA
      regulation. Using an in vivo rat model with regional myocardial ischemia, we
      treated young (2-4 months) and aged (22-24 months) Wistar rats with PKA activator
      forskolin, BK(Ca) channel activator NS1619 and/or BK(Ca) channel blocker
      iberiotoxin. Forskolin induced infarct size reduction was 1) age-dependent and 2)
      prevented by iberiotoxin. The effect of forskolin on myocardial PKA activity was
      comparable in young and aged animals. In addition, NS1619 initiated
      cardioprotection also in the aged heart both when administered before ischemia
      and during early reperfusion phase. Activation of BK(Ca) channels is critically
      involved in forskolin induced cardioprotection. The age-dependency of forskolin
      induced cardioprotection is not caused by age-dependent differences in PKA
      activation. Pharmacological targeting of BK(Ca) channels before or after
      myocardial ischemia is a promising therapeutic strategy to protect the aged heart
      from ischemia and reperfusion injury.

PMID- 24727218
TI  - An assessment of firework particle persistence on the hands and related police
      force practices in relation to GSR evidence.
AB  - In a previous study by Grima et al. Sci. Justice 52 (1) (2012) 49, it was shown
      that background particles can aid in the exclusion of firework particles which
      are indistinguishable from GSR. Issues relating to the persistence of such
      particle populations were presented. The scope of this project was to examine
      persistence on the hands in the context of possible post-display scene
      contamination and how this can affect GSR evidence, especially in light of
      possible GSR/firework mixtures. Persistence was investigated by recovering
      firework residues eight hours post-display following contact of the hands with
      bedding. In addition, particle profiling was carried out using SEM-EDX. Firework
      particle populations exhibited strong persistence in all displays, with not less
      than 667 particles persisting in each scenario. This factor challenges GSR
      evidence, especially if personnel stationed at display sites enter scenes of
      crime or come into contact with suspects after a display. A survey of UK police
      force practices following firework displays showed that authorities are not aware
      of the impact particle transfer may have on GSR evidence. Recommendations for the
      implementation of basic hygiene practices for particle transfer control have also
      been made. 

PMID- 24727219
TI  - Profiling the approach to the investigation of viral infections in cases of
      sudden unexpected death in infancy in the Western Cape Province, South Africa.
AB  - BACKGROUND: Sudden unexpected death in infancy is one of the main contributory
      factors to high infant mortality rates world-wide. Several risk factors,
      including viral infection, have been implicated in SUDI cases, but no single
      factor has been confirmed as the main cause of death. At the Tygerberg Medico
      legal Laboratory, Cape Town, South Africa, investigation of lung tissue for viral
      infection forms part of an institutional protocol for the examination of cases of
      sudden unexpected death in infancy. METHODS: Lung tissue from 82 cases of sudden
      unexpected death in infancy was collected over a 10 month period. Routine shell
      vial cultures and histological examination of the tissue were performed according
      to the standard institutional protocol on fresh and formalin-fixed tissue,
      respectively. In addition, real-time polymerase chain reactions and
      immunohistochemical staining for adenovirus, cytomegalovirus and respiratory
      syncytial virus were done on fresh and formalin-fixed lung tissue, respectively.
      RESULTS: Huge variation was found in the number of positive cases confirmed by
      shell vial culture, real-time polymerase chain reaction and immunohistochemistry
      (0, 2 and 0 for adenovirus; 3, 29 and 2 for cytomegalovirus; and 0, 0 and 4 for
      respiratory syncytial virus, respectively). CONCLUSIONS: In the absence of a
      National Protocol for investigation of sudden unexpected death in infancy, we
      conclude that the selection of viruses and routine diagnostic technique included
      in the institutional investigation protocol might be suboptimal and should be re
      evaluated.

PMID- 24727220
TI  - Child sexual abuse--Medical statement conclusions in criminal legal process.
AB  - OBJECTIVES: To evaluate medical statement conclusions in the criminal-legal
      process in suspected cases of child sexual abuse (CSA). STUDY DESIGN: An
      observational study of a random sample of 130 medically examined, police reported
      CSA suspected cases during 2001-2009. Medical statements were evaluated and their
      conclusions were analyzed with an end-point in the legal process. The data
      consists of official investigation documents from the University Hospital
      records, the Police, crime laboratories, the State Prosecutor, and the Courts of
      Law. RESULTS: The median age of the children was 5.3 years (range 11 months-17.3
      years) at the time of the suspected sexual abuse. In most cases (76.2%, 99/130)
      medical statement conclusions neither supported nor excluded the suspicion of
      CSA. Twenty-one (16.2%) medical statements supported and in 10 cases (7.7%) the
      conclusion did not support the suspected CSA. Of the suspected CSA cases a
      hundred (76.9%) proceeded to the Prosecutor. The charge filing rate was 41.5%
      (54/130). The final conviction rate was 30.8% (40/130) and 74% in the charged
      cases. Medical statements were mentioned as evidence in the Prosecutor's decision
      to file charges in 18 (33.3%) of suspected CSA cases and in 15 (36%) of verdicts.
      A child's clear disclosure of CSA (p<0.001) and medical statements (p=0.037) had
      a significant role in decision making on convictions. CONCLUSION: In medical
      statement conclusions, physical findings with proper documentation and
      interpretation are needed to avoid misunderstandings in the legal process. The
      present study supports a routine medical statement peer review to minimize the
      risk of neglect caused by lack of knowledge among authorities working with
      sexually abused children.

PMID- 24727221
TI  - Introduction to the special issue of Neurobiology of Learning and Memory on fear
      extinction.

PMID- 24727222
TI  - Adaptation of iron homeostasis pathways by a Pseudomonas aeruginosa pyoverdine
      mutant in the cystic fibrosis lung.
AB  - Cystic fibrosis (CF) patients suffer from chronic bacterial lung infections, most
      notably by Pseudomonas aeruginosa, which persists for decades in the lungs and
      undergoes extensive evolution. P. aeruginosa requires iron for virulence and uses
      the fluorescent siderophore pyoverdine to scavenge and solubilize ferric iron
      during acute infections. Pyoverdine mutants accumulate in the lungs of some CF
      patients, however, suggesting that the heme and ferrous iron acquisition pathways
      of P. aeruginosa are more important in this environment. Here, we sought to
      determine how evolution of P. aeruginosa in the CF lung affects iron acquisition
      and regulatory pathways through the use of longitudinal CF isolates. These
      analyses demonstrated a significant reduction of siderophore production during
      the course of CF lung infection in nearly all strains tested. Mass spectrometry
      analysis of one of these strains showed that the later CF isolate has streamlined
      the metabolic flux of extracellular heme through the HemO heme oxygenase,
      resulting in more-efficient heme utilization. Moreover, gene expression analysis
      shows that iron regulation via the PrrF small RNAs (sRNAs) is enhanced in the
      later CF isolate. Finally, analysis of P. aeruginosa gene expression in the lungs
      of various CF patients demonstrates that both PrrF and HemO are consistently
      expressed in the CF lung environment. Combined, these results suggest that heme
      is a critical source of iron during prolonged infection of the CF lung and that
      changes in iron and heme regulatory pathways play a crucial role in adaptation of
      P. aeruginosa to this ever-changing host environment. 

PMID- 24727223
TI  - Construction and characterization of tetH overexpression and knockout strains of
      Acidithiobacillus ferrooxidans.
AB  - Acidithiobacillus ferrooxidans is a major participant in consortia of
      microorganisms used for bioleaching. It can obtain energy from the oxidation of
      Fe(2+), H2, S(0), and various reduced inorganic sulfur compounds (RISCs).
      Tetrathionate is a key intermediate during RISC oxidation, hydrolyzed by
      tetrathionate hydrolase (TetH), and used as sole energy source. In this study, a
      tetH knockout (DeltatetH) mutant and a tetH overexpression strain were
      constructed and characterized. The tetH overexpression strain grew better on
      sulfur and tetrathionate and possessed a higher rate of tetrathionate utilization
      and TetH activity than the wild type. However, its cell yields on tetrathionate
      were much lower than those on sulfur. The DeltatetH mutant could not grow on
      tetrathionate but could proliferate on sulfur with a lower cell yield than the
      wild type's, which indicated that tetrathionate hydrolysis is mediated only by
      TetH, encoded by tetH. The DeltatetH mutant could survive in ferrous medium with
      an Fe(2+) oxidation rate similar to that of the wild type. For the tetH
      overexpression strain, the rate was relatively higher than that of the wild type.
      The reverse transcription-quantitative PCR (qRT-PCR) results showed that tetH and
      doxD2 acted synergistically, and doxD2 was considered important in thiosulfate
      metabolism. Of the two sqr genes, AFE_0267 seemed to play as important a role in
      sulfide oxidation as AFE_1792. This study not only provides a substantial basis
      for studying the function of the tetH gene but also may serve as a model to
      clarify other candidate genes involved in sulfur oxidation in this organism. 

PMID- 24727224
TI  - Arginine deiminase in Staphylococcus epidermidis functions to augment biofilm
      maturation through pH homeostasis.
AB  - Allelic replacement mutants were constructed within arginine deiminase (arcA1 and
      arcA2) to assess the function of the arginine deiminase (ADI) pathway in organic
      acid resistance and biofilm formation of Staphylococcus epidermidis 1457. A
      growth-dependent acidification assay (pH ~5.0 to ~5.2) determined that strain
      1457 devoid of arginine deiminase activity (1457 DeltaADI) was significantly less
      viable than the wild type following depletion of glucose and in the presence of
      arginine. However, no difference in viability was noted for individual 1457
      DeltaarcA1 (native) or DeltaarcA2 (arginine catabolic mobile element [ACME]
      derived) mutants, suggesting that the native and ACME-derived ADIs are
      compensatory in S. epidermidis. Furthermore, flow cytometry and electron
      paramagnetic resonance spectroscopy results suggested that organic acid stress
      resulted in oxidative stress that could be partially rescued by the iron chelator
      dipyridyl. Collectively, these results suggest that formation of hydroxyl
      radicals is partially responsible for cell death via organic acid stress and that
      ADI-derived ammonia functions to counteract this acid stress. Finally, static
      biofilm assays determined that viability, ammonia synthesis, and pH were reduced
      in strain 1457 DeltaADI following 120 h of growth in comparison to strain 1457
      and the arcA1 and arcA2 single mutants. It is hypothesized that ammonia synthesis
      via the ADI pathway is important to reduce pH stress in specific microniches that
      contain high concentrations of organic acids. 

PMID- 24727225
TI  - CugP is a novel ubiquitous non-GalU-type bacterial UDP-glucose pyrophosphorylase
      found in cyanobacteria.
AB  - UDP-glucose pyrophosphorylase synthesizes UDP-glucose from UTP and glucose 1
      phosphate and exists in almost all species. Most bacteria possess a GalU-type UDP
      glucose pyrophosphorylase, whereas many cyanobacteria species do not. In certain
      cyanobacteria, UDP-glucose is used as a substrate for synthesis of
      exopolysaccharide cellulose in spite of the absence of GalU-type UDP-glucose
      pyrophosphorylase. Therefore, there should be an uncharacterized UDP-glucose
      pyrophosphorylase in cyanobacteria. Here, we show that all cyanobacteria possess
      a non-GalU-type bacterial UDP-glucose pyrophosphorylase, i.e., CugP, a novel
      family in the nucleotide triphosphate transferase superfamily. The expressed
      recombinant Synechocystis sp. strain PCC 6803 CugP had pyrophosphorylase activity
      that was highly specific for UTP and glucose 1-phosphate. The fact that the CugP
      gene cannot be deleted completely in Synechocystis sp. PCC 6803 suggests its
      central role as the substrate supplier for galactolipid synthesis. Galactolipids
      are major constituents of the photosynthetic thylakoid membrane and important for
      photosynthetic activity. Based on phylogenetic analysis, this CugP-type UDP
      glucose pyrophosphorylase may have recently been horizontally transferred to
      certain noncyanobacteria. 

PMID- 24727226
TI  - Identification and characterization of a gene cluster required for proper rod
      shape, cell division, and pathogenesis in Clostridium difficile.
AB  - Little is known about cell division in Clostridium difficile, a strict anaerobe
      that causes serious diarrheal diseases in people whose normal intestinal
      microbiome has been perturbed by treatment with broad-spectrum antibiotics. Here
      we identify and characterize a gene cluster encoding three cell division proteins
      found only in C. difficile and a small number of closely related bacteria. These
      proteins were named MldA, MldB, and MldC, for midcell localizing division
      proteins. MldA is predicted to be a membrane protein with coiled-coil domains and
      a peptidoglycan-binding SPOR domain. MldB and MldC are predicted to be
      cytoplasmic proteins; MldB has two predicted coiled-coil domains, but MldC lacks
      obvious conserved domains or sequence motifs. Mutants of mldA or mldB had
      morphological defects, including loss of rod shape (a curved cell phenotype) and
      inefficient separation of daughter cells (a chaining phenotype). Fusions of cyan
      fluorescent protein (CFP) to MldA, MldB, and MldC revealed that all three
      proteins localize sharply to the division site. This application of CFP was
      possible because we discovered that O2-dependent fluorescent proteins produced
      anaerobically can acquire fluorescence after cells are fixed with cross-linkers
      to preserve native patterns of protein localization. Mutants lacking the Mld
      proteins are severely attenuated for pathogenesis in a hamster model of C.
      difficile infection. Because all three Mld proteins are essentially unique to C.
      difficile, they might be exploited as targets for antibiotics that combat C.
      difficile without disrupting the intestinal microbiome. 

PMID- 24727227
TI  - Involvement of rppH in thermoregulation in Pseudomonas syringae.
AB  - Temperature, among other environmental factors, influences the incidence and
      severity of many plant diseases. Likewise, numerous traits, including the
      expression of virulence factors, are regulated by temperature. Little is known
      about the underlying genetic determinants of thermoregulation in plant-pathogenic
      bacteria. Previously, we showed that the expression of both fliC (encoding
      flagellin) and syfA (encoding a nonribosomal polypeptide synthetase) was
      suppressed at high temperatures in Pseudomonas syringae. In this work, we used a
      high-throughput screen to identify mutations that conferred overexpression of
      syfA at elevated temperatures (28 degrees C compared to 20 degrees C). Two genes,
      Psyr_2474, encoding an acyl-coenzyme A (CoA) dehydrogenase, and Psyr_4843,
      encoding an ortholog of RppH, which in Escherichia coli mediates RNA turnover,
      contribute to thermoregulation of syfA. To assess the global role of rppH in
      thermoregulation in P. syringae, RNA sequencing was used to compare the
      transcriptomes of an rppH deletion mutant and the wild-type strain incubated at
      20 degrees C and 30 degrees C. The disruption of rppH had a large effect on the
      temperature-dependent transcriptome of P. syringae, affecting the expression of
      569 genes at either 20 degrees C or 30 degrees C but not at both temperatures.
      Intriguingly, RppH is involved in the thermoregulation of ribosome-associated
      proteins, as well as of RNase E, suggesting a prominent role of rppH on the
      proteome in addition to its effect on the transcriptome. 

PMID- 24727229
TI  - Metabolic disposition and excretion of quinocetone in rats, pigs, broilers, and
      carp.
AB  - Excretion, disposition, and metabolism of [(3)H]-quinocetone in rats, pigs,
      broilers, and carp following oral administration were investigated. After a
      single p.o. dose, total radioactivity was rapidly excreted, with ?94% in all
      species within 14 days. Fecal excretion of radioactivity was 68% and 65% of the
      administered dose in rats and pigs, respectively, with the remainder excreted in
      the urine. Six hours after the last of seven daily oral administrations of (3)H
      labeled QCT, radioactivity was found to be distributed throughout all tissues,
      with the majority of radioactivity cleared within 7 days, and elimination was the
      slowest from the liver and kidney. QCT was extensively metabolized in all of the
      species, and the primary changes included N-O group reduction, carbonyl group
      reduction, double bond reduction, and hydroxylation. The major tissue metabolites
      of QCT were Q2, Q4, Q5, Q8, and Q9 in rats; Q1, Q2, Q3, Q4, and Q5 in pigs; Q1,
      Q2, Q3, Q4, and Q7 in broilers; and Q1, Q2 in carp. This confirmed the potential
      link between QCT metabolism through N-O group reduction and its organ toxicity.
      The results of the present study provide important data that could help
      understand the relationship between the toxicities and metabolic disposition of
      QCT.

PMID- 24727228
TI  - The SdiA-regulated gene srgE encodes a type III secreted effector.
AB  - Salmonella enterica serovar Typhimurium is a food-borne pathogen that causes
      severe gastroenteritis. The ability of Salmonella to cause disease depends on two
      type III secretion systems (T3SSs) encoded in two distinct Salmonella
      pathogenicity islands, 1 and 2 (SPI1 and SPI2, respectively). S. Typhimurium
      encodes a solo LuxR homolog, SdiA, which can detect the acyl-homoserine lactones
      (AHLs) produced by other bacteria and upregulate the rck operon and the srgE
      gene. SrgE is predicted to encode a protein of 488 residues with a coiled-coil
      domain between residues 345 and 382. In silico studies have provided conflicting
      predictions as to whether SrgE is a T3SS substrate. Therefore, in this work, we
      tested the hypothesis that SrgE is a T3SS effector by two methods, a beta
      lactamase activity assay and a split green fluorescent protein (GFP)
      complementation assay. SrgE with beta-lactamase fused to residue 40, 100, 150, or
      300 was indeed expressed and translocated into host cells, but SrgE with beta
      lactamase fused to residue 400 or 488 was not expressed, suggesting interference
      by the coiled-coil domain. Similarly, SrgE with GFP S11 fused to residue 300, but
      not to residue 488, was expressed and translocated into host cells. With both
      systems, translocation into host cells was dependent upon SPI2. A phylogenetic
      analysis indicated that srgE is found only within Salmonella enterica subspecies.
      It is found sporadically within both typhoidal and nontyphoidal serovars,
      although the SrgE protein sequences found within typhoidal serovars tend to
      cluster separately from those found in nontyphoidal serovars, suggesting
      functional diversification. 

PMID- 24727230
TI  - The effect of oxidized cholesterol on barrier functions and IL-10 mRNA expression
      in human intestinal epithelium co-cultured with dendritic cells in the transwell
      system.
AB  - The intestinal epithelium is exposed to oxygenated cholesterol products present
      in foodstuffs. In vitro studies demonstrate the effect of oxysterols on cytokine
      release by intestinal cells cultured alone. However, physiologically, the
      response of the intestinal epithelium to external agents occurs in the presence
      of dendritic cells (DCs). The aim of the study was to analyze the effect of 7
      ketocholesterol on the barrier functions and IL-10 mRNA expression of Caco-2
      cells in the presence of DCs, and secondly, on IL-10 mRNA expression in DCs. Caco
      2 cells were co-cultured with monocyte-derived dendritic cells and induced with 7
      ketocholesterol in a transwell system. DCs did not affect the transepithelial
      electrical resistance (TER) of the Caco-2 cell monolayer, but increased IL-10
      mRNA expression in Caco-2 cells. 7-ketocholesterol decreased the TER of Caco-2
      cells co-cultured with DCs and diminished IL-10 mRNA expression in Caco-2 cells
      induced by the presence of DCs. IL-10 mRNA expression fell in DCs co-cultured
      with Caco-2 cells after treatment with 7-ketocholesterol. Oxidized cholesterols
      present in gut mucosa may contribute to the decrease of epithelial barrier
      functions and the inappropriate development of an inflammatory response to food
      compounds. 

PMID- 24727231
TI  - Electronic structure and magnetic properties of iridate superlattice
      SrIrO(3)/SrTiO(3).
AB  - Motivated by an experimental report of iridate superlattices, we performed first
      principle electronic structure calculations for SrIrO3/SrTiO3. Heterostructuring
      causes SrIrO3 to become Sr2IrO4-like, and the system has the well-defined jeff =
      1/2 states near the Fermi level as well as a canted antiferromagnetic order
      within the quasi-two-dimensional IrO2 plane. In response to a larger tensile
      strain, the band gap is increased due to the resulting increase in bond length
      and the bandwidth reduction. The ground state magnetic properties are discussed
      in comparison to the metastable collinear antiferromagnetic state. Our work sheds
      new light on understanding the recent experimental results on the iridate
      heterostructures. 

PMID- 24727232
TI  - Comments on "OARSI guidelines for the non-surgical management of knee
      osteoarthritis".

PMID- 24727233
TI  - Dietary fats and cardiovascular disease: putting together the pieces of a
      complicated puzzle.
AB  - Dietary fatty acids play significant roles in the cause and prevention of
      cardiovascular disease (CVD). Trans fatty acids from partially hydrogenated
      vegetable oils have well-established adverse effects and should be eliminated
      from the human diet. CVD risk can be modestly reduced by decreasing saturated
      fatty acids (SFA) and replacing it by a combination of polyunsaturated fatty
      acids (PUFA) and monounsaturated fatty acids (MUFA). Although the ideal type of
      unsaturated fat for this replacement is unclear, the benefits of PUFA appear
      strongest. Both n-6 and n-3 PUFA are essential and reduce CVD risk. However,
      additional research is needed to better define the optimal amounts of both and to
      discern the patients and/or general population that would benefit from
      supplemental n-3 fatty acid intake. Furthermore, consumption of animal products,
      per se, is not necessarily associated with increased CVD risk, whereas nut and
      olive oil intake is associated with reduced CVD risk. In conclusion, the total
      matrix of a food is more important than just its fatty acid content in predicting
      the effect of a food on CVD risk, and a healthy diet should be the cornerstone of
      CVD prevention.

PMID- 24727234
TI  - Comparison of effects of pioglitazone and glimepiride on plasma soluble RAGE and
      RAGE expression in peripheral mononuclear cells in type 2 diabetes: randomized
      controlled trial (PioRAGE).
AB  - OBJECTIVE: The receptor for advanced glycation end-products (RAGE) is involved in
      vascular complications in diabetic patients. Pioglitazone, in contrast to
      glimepiride, has been shown to be protective against atherosclerotic disorders.
      In this study, we directly compared the effects of those drugs on RAGE system.
      METHODS: Sixty-three type 2 diabetic patients (age 20-80 years, hemoglobin A1c
      6.4-10.3%) being treated with sulfonylurea (glimepiride 0.5-2.0 mg/day,
      glyclazide 20-80 mg/day, glibenclamide 1.25-5.0 mg/day), or with nateglinide or
      metiglynide were randomly assigned to receive either pioglitazone (n = 31) or
      glimepiride (n = 32). Levels in plasma of soluble RAGE (sRAGE) and endogenous
      secretory RAGE (esRAGE), and RAGE expression in peripheral mononuclear cells were
      determined at 0, 12, and 24 weeks. RESULTS: Twenty-seven patients in the
      pioglitazone group (15-30 mg) and 30 in the glimepiride group (0.5-4 mg)
      completed the 24-week trial. Increases in plasma esRAGE were significantly
      greater in the pioglitazone group (12 weeks: 55 +/- 15 pg/mL, p = 0.018; 24
      weeks: 90 +/- 14 pg/mL, p = 0.003) as compared to the glimepiride group (12
      weeks: 12 +/- 9 pg/mL; 24 weeks: 29 +/- 14 pg/mL). Increases in plasma sRAGE were
      also significantly (p = 0.037) higher in the pioglitazone group at 24 weeks (170
      +/- 166 vs.74 +/- 171 pg/mL). Furthermore, RAGE expression in mononuclear cells
      was significantly (p = 0.008) decreased to a greater degree in the pioglitazone
      group at 24 weeks (-7.39 +/- 5.18 vs. -3.39 +/- 5.72 MFI). Changes in HbA1c, IRI,
      and insulin resistance index (HOMA) at 24 weeks were not significantly different
      between the groups. CONCLUSION: Pioglitazone suppresses RAGE expression and
      increases circulating sRAGE/esRAGE, and those activities are not necessarily
      dependent on plasma glucose or insulin resistance levels. CLINICAL TRIAL NO:
      UMIN000002055.

PMID- 24727236
TI  - Cholecalciferol (vitamin D 3) improves cognitive dysfunction and reduces
      inflammation in a rat fatty liver model of metabolic syndrome.
AB  - AIM: The aim of this study was to examine the effects of cholecalciferol on
      systemic inflammation and memory in the setting of fatty liver disease in rats.
      MATERIALS AND METHODS: To induce the development of fatty liver disease, the rats
      were fed a 35% fructose solution over 8 weeks. Group I (n=6) was designated as
      the control group and fed with standard rat chow. Group II (n=6) was provided
      with, standard rat chow, and 0.3 MUg/kg/day of oral cholecalciferol over a
      duration of 2 weeks. In addition to standard rat chow, group III (n=6) and group
      IV (n=6) were given 4 mL of the 35% fructose solution per day via oral gavage for
      8 weeks. However, group IV was also given 0.3 MUg/kg/day of oral cholecalciferol
      over 2 weeks. After the treatment period, passive avoidance tasks were performed
      by all groups. The liver and brain were harvested for subsequent biochemical and
      histopathologic analyses. KEY FINDINGS: The development of fatty liver extends
      the memory latency period of passively avoiding tasks after 1 trial. Moreover,
      there were increases in brain TNF-alpha and plasma MDA levels according to two
      way analysis of variance. Cholecalciferol supplementation decreased the latency
      period of passively avoiding tasks in rats with hepatosteatosis, and also
      significantly reduced brain TNF-alpha and plasma MDA levels. SIGNIFICANCE: Fatty
      liver may contribute to the development of systemic inflammation, which affects
      cognition and causes deficits in memory; however, the anti-inflammatory and
      antioxidant properties of vitamin D may improve the cognitive function of rats
      with hepatosteatosis.

PMID- 24727235
TI  - Damage of the endothelial glycocalyx in chronic kidney disease.
AB  - BACKGROUND AND OBJECTIVES: The endothelial glycocalyx (eGC), a mesh of anionic
      biopolymers covering the luminal surface of endothelial cells, is considered as
      an intravascular compartment that protects the vessel wall against pathogenic
      insults in cardiovascular disease. We hypothesized that chronic kidney disease
      (CKD) is associated with reduced eGC integrity and subsequent endothelial
      dysfunction. METHODS & RESULTS: Shedding of two major components of the eGC,
      namely syndecan-1 (Syn-1) and hyaluronan (HA), was measured by ELISA in 95
      patients with CKD (stages 3-5) and 31 apparently healthy controls. Plasma levels
      of Syn-1 and HA increased steadily across CKD stages (5- and 5.5-fold,
      respectively P < 0.001) and were independently associated with impaired renal
      function after multivariate adjustment. Furthermore, Syn-1 and HA correlated
      tightly with plasma markers of endothelial dysfunction such as soluble fms-like
      tyrosine kinase-1 (sFlt-1), soluble vascular adhesion molecule-1 (sVCAM-1), von
      Willebrand-Factor (vWF) and angiopoietin-2 (P < 0.001). Experimentally, excessive
      shedding of the eGC, evidenced by 11-fold increased Syn-1 plasma levels, was also
      observed in an established rat model of CKD, the 5/6-nephrectomized rats.
      Consistently, an atomic force microscopy-based approach evidenced a significant
      decrease in eGC thickness (360 +/- 79 vs. 157 +/- 29 nm, P = 0.001) and stiffness
      (0.33 +/- 0.02 vs. 0.22 +/- 0.01 pN/nm, P < 0.001) of aorta endothelial cell
      explants isolated from CKD rats. CONCLUSION: Our findings provide evidence for
      damage of the atheroprotective eGC as a consequence of CKD and potentially open a
      new avenue to pathophysiology and treatment of cardiovascular disease in renal
      patients.

PMID- 24727237
TI  - Effects of intrathecal opioids combined with low-dose naloxone on motilin and its
      receptor in a rat model of postoperative pain.
AB  - AIMS: To investigate the effects of intrathecal morphine and fentanyl combined
      with low-dose naloxone on the expression of motilin and its receptor in a rat
      model of postoperative pain. MAIN METHODS: An intrathecal catheter was implanted,
      and saline, opioids (morphine and fentanyl) and naloxone were intrathecally
      administered 7 days later. An incisional pain model was established to induce
      pain behaviors in rats by unilateral plantar incision. Thermal hyperalgesia and
      mechanical allodynia were measured by using a radiant heat and electronic Von
      Frey filament, respectively. The expression of motilin in the hippocampus,
      stomach, duodenum, and plasma was determined by ELISA; and the expression of
      motilin receptor in the hippocampus was detected by Western blot assay. KEY
      FINDINGS: Motilin and its receptor were detected in the hippocampus. Acute
      incisional pain increased the motilin expression in the hippocampus and duodenum,
      while decreasing its expression in the gastric body and plasma. Postoperative
      analgesia with morphine+fentanyl upregulated the expression of motilin in the
      hippocampus; however, motilin was downregulated in peripheral sites. Naloxone at
      1 ng/kg restored motilin to baseline levels. Acute pain, morphine+fentanyl, and
      naloxone all induced the expression of motilin receptor in the hippocampus.
      SIGNIFICANCE: Acute pain, postoperative analgesia with opioids, and naloxone
      significantly impacted the expression of hippocampal and peripheral motilin.
      Variation trends in all sites were not identical. Intrathecal injection of low
      dose naloxone upregulated paw withdrawal thermal latency and enhanced the
      analgesic effects of opioids. The findings presented here provide a new basis for
      central and peripheral regulations in GI motility, clinical postoperative
      analgesia, and management of analgesic complications.

PMID- 24727238
TI  - Evaluation of mutagenic and genotoxic activities of lobeline and its modulation
      on genomic instability induced by ethanol.
AB  - AIM: Lobeline is a natural alkaloid derived from Lobelia inflata that has been
      investigated as a clinical candidate for the treatment of alcoholism. In a pre
      clinical trial, lobeline decreased the preference for and consumption of ethanol,
      due to the modulation of the nicotinic acetylcholine receptor. However, the
      interaction between lobeline and ethanol is poorly known and thus there are
      safety concerns. The present study was conducted to evaluate the mutagenic and
      genotoxic effects of lobeline and assess its modulation of ethanol-induced
      toxicological effects. MAIN METHODS: CF-1 male mice were divided into five
      groups. Groups received an intraperitoneal injection of saline solution, lobeline
      (5 or 10mg/kg), ethanol (2.5 g/kg), or lobeline plus ethanol, once a day for
      three consecutive days. Genotoxicity was evaluated in peripheral blood using the
      alkaline comet assay. The mutagenicity was evaluated using both
      Salmonella/microsome assay in TA1535, TA97a, TA98, TA100, and TA102 Salmonella
      typhimurium strains and the micronucleus test in bone marrow. Possible liver and
      kidney injuries were evaluated using biochemical analysis. KEY FINDINGS: Lobeline
      did not show genotoxic or mutagenic effects and did not increase the ethanol
      induced genotoxic effects in blood. Lobeline also protected blood cells against
      oxidative damage induced by hydrogen peroxide. Biochemical parameters were not
      altered, indicating no liver or kidney injuries or alterations in lipid and
      carbohydrate metabolisms. SIGNIFICANCE: These findings suggest that lobeline does
      not induce gene or chromosomal mutations, and that this lack of genetic toxicity
      is maintained in the presence of ethanol, providing further evidence of the
      safety of this drug to treat alcohol dependence.

PMID- 24727239
TI  - Expression of microRNAs, CYP1A1 and CYP2B1 in the livers and ovaries of female
      rats treated with DDT and PAHs.
AB  - AIMS: In this study, we determined the expression level of miRNAs and the
      induction of CYP1A1 and CYP2B1 in the livers and ovaries of female Wistar rats
      treated with DDT, benzo[a]pyrene (BP), and 3-methylcholanthrene (MC). This study
      compared CYP1A/2B induction and miRNA expression levels to cast light on a
      possible role of miRNA in the tissue-specific induction of CYPs. MAIN METHODS:
      The induction of CYP1A1/2B1 enzymes was detected by ethoxy-, pentoxyresorufin O
      dealkylation and Western blot analysis. The CYP1A1/2B1 gene expression was
      determined by RT-real time PCR. Relative levels of expression for selected in
      silico miR species were determined by real time PCR with small nuclear U6 RNA
      employed as a reference gene. KEY FINDINGS: After bioinformatic analysis, miR-21,
      221, 222, and 429 were chosen as potential post-transcriptional regulators of rat
      CYP1A and CYP2B. It was shown that miR-21, 221, 222, and 429 expression levels
      decreased in the liver of DDT-, BP-, and MC-treated rats, whereas increases were
      observed in CYP1A1 and CYP2B1 mRNA expression levels and protein content, and
      EROD and PROD activities. Conversely, a tendency for elevated levels of miRNAs in
      the ovaries of inducer-treated female rats was observed. In the ovaries, a high
      level of CYP1A1 and CYP2B1 mRNA expression was observed, although protein content
      and enzyme activity were not visible. SIGNIFICANCE: These data suggest a
      potential involvement of miRNA in the post-transcriptional regulation of CYP1A
      and CYP2B in the livers and ovaries of chemically induced rats.

PMID- 24727240
TI  - Neuroprotective role of quercetin in locomotor activities and cholinergic
      neurotransmission in rats experimentally demyelinated with ethidium bromide.
AB  - AIM: The purpose of this study was to investigate whether the flavonoid quercetin
      can prevent alterations in the behavioral tests and of cholinergic
      neurotransmission in rats submitted to the ethidium bromide (EB) experimental
      demyelination model during events of demyelination and remyelination. MAIN
      METHODS: Wistar rats were randomly distributed into four groups (20 animals per
      group): Control (pontine saline injection and treatment with ethanol), Querc
      (pontine saline injection and treatment with quercetin), EB (pontine 0.1% EB
      injection and treatment with ethanol), and EB+Querc (pontine 0.1% EB injection
      and treatment with quercetin). The groups Querc and Querc+EB were treated once
      daily with quercetin (50mg/kg) diluted in 25% ethanol solution (1ml/kg) and the
      animals of the control and EB groups were treated once daily with 25% ethanol
      solution (1ml/kg). Two stages were observed: phase of demyelination (peak on day
      7) and phase of remyelination (peak on day 21 post-injection). Behavioral tests
      (beam walking, foot fault and inclined plane test), acetylcholinesterase (AChE)
      activity and lipid peroxidation in pons, cerebellum, hippocampus, hypothalamus,
      striatum and cerebral cortex were measured. KEY FINDINGS: The quercetin promoted
      earlier locomotor recovery, suggesting that there was demyelination prevention or
      further remyelination velocity as well as it was able to prevent the inhibition
      of AChE activity and the increase of lipidic peroxidation, suggesting that this
      compound can protect cholinergic neurotransmission. SIGNIFICANCE: These results
      may contribute to a better understanding of the neuroprotective role of quercetin
      and the importance of an antioxidant diet in humans to provide benefits in
      neurodegenerative diseases such as MS.

PMID- 24727241
TI  - Synthesis, antiproliferative and anti-dengue virus evaluations of 2-aroyl-3
      arylquinoline derivatives.
AB  - A number of 2-aroyl-3-arylquinoline derivatives was synthesized and evaluated for
      their anti-Dengue virus activity. Both 2-(hydroxyphenylmethyl)-3-(4
      methoxyphenyl)quinoline (13a) and 2-(4-hydroxybenzoyl)-3-(4
      hydroxyphenyl)quinoline (17) were found to significantly inhibit the DENV2 RNA
      expression in Huh-7-DV-Fluc cells with a potency approximately equal to that of
      ribavirin and the inhibition is in a dose-dependent manner. Compounds 13a and 17
      reduced DENV replication in both viral protein and mRNA levels, and no
      significant cell cytotoxicity was detected, with greater than 50% viability of
      Huh-7-DV-Fluc cells at a concentration of 100 MUM. However, significant
      cytotoxicity was detected for the positive ribavirin. In addition, we performed
      infectious assay to further verify the inhibitory activity of 13a and 17 on DENV
      replication in protein and RNA levels. On the other hand, compounds 19a-19c
      exhibited IC50 values ranged from 4.47 to 8.68 MUM against A549, H1299, MCF-7,
      and Huh-7 which were approximately equal potent to the positive topotecan.
      Structural optimization of lead compounds, 13a and 17, and their detailed
      molecular mechanism of action are ongoing. 

PMID- 24727242
TI  - Development of fluorescent double-strand probes labeled with 8-(p-CF3-cinnamyl)
      adenosine for the detection of cyclin D1 breast cancer marker.
AB  - Fluorescent nucleoside analogs replacing natural DNA bases in an oligonucleotide
      have been widely used for the detection of genetic material. Previously, we have
      described 2-((4-(trifluoromethyl) phenyl)-trans-vinyl)-2'-deoxy-adenosine, 6, a
      nucleoside analog with intrinsic fluorescence (NIF). Analog 6 exhibits a quantum
      yield 3115-fold higher than that of adenosine (phi 0.81) and maximum emission
      which is 120 nm red shifted (lambdaem 439 nm). Here, we incorporated this analog
      in one or several positions of cyclin D1-targeting 15-mer oligonucleotides (ONs).
      The fluorescence of 6 was quenched upon incorporation into an oligonucleotide
      (ca. 1.5-22 fold), and was further reduced upon duplex formation. Specifically,
      ON7 exhibited a fluorescence decrease of ca. 2- or 3-fold upon duplex formation
      with complementary DNA or RNA strand, respectively. We determined the kinetics of
      dehybridization/rehybridization process in the presence of ssDNA or ssRNA targets
      to optimize our probes length and established the probes' selectivity towards a
      specific target. Furthermore, we proved specificity of our probe to the target
      vs. singly mismatched targets. Our most promising ds-NIF-probe, ON7:RNA, was used
      for the detection of cyclin D1 mRNA marker in cancerous cells total RNA extracts.
      The ds-probe specifically recognized the target as observed by a 2-fold
      fluorescence increase within 30 s at RT. These findings illustrate the potential
      of ds-NIF-probes for the diagnosis of breast cancer. 

PMID- 24727243
TI  - Novel metronidazole-chalcone conjugates with potential to counter drug resistance
      in Trichomonas vaginalis.
AB  - Trichomoniasis is the most prevalent, curable sexually transmitted disease (STD),
      which increases risk of viral STDs and HIV. However, drug resistance has been
      developed by some strains of Trichomonas vaginalis against Metronidazole (MTZ),
      the FDA approved drug against trichomoniasis. In the present study twenty two
      chalcone hybrids of metronidazole have been synthesized in a quest to get new
      molecules with higher potential against metronidazole-resistant T. vaginalis. All
      new hybrid molecules were found active against T. vaginalis with varying levels
      of activity against MTZ-susceptible and resistant strains. Eight compounds (4a,
      4c, 4d, 4e, 4f, 4h, 4q and 4s) were found as active as the standard drug with an
      MIC of 1.56 MUg/ml against MTZ-susceptible strain. However, compounds 4e, 4h and
      4m were 4-times more active than MTZ against drug-resistant T. vaginalis, amongst
      which 4e and 4h were most promising against both susceptible and resistant
      strains. 

PMID- 24727244
TI  - HDAC signaling in neuronal development and axon regeneration.
AB  - The development and repair of the nervous system requires the coordinated
      expression of a large number of specific genes. Epigenetic modifications of
      histones represent an essential principle by which neurons regulate
      transcriptional responses and adapt to environmental cues. The post-translational
      modification of histones by chromatin-modifying enzymes histone
      acetyltransferases (HATs) and histone deacetylases (HDACs) shapes chromatin to
      adjust transcriptional profiles during neuronal development. Recent observations
      also point to a critical role for histone acetylation and deacetylation in the
      response of neurons to injury. While HDACs are mostly known to attenuate
      transcription through their deacetylase activity and their interaction with co
      repressors, these enzymes are also found in the cytoplasm where they display
      transcription-independent activities by regulating the function of diverse
      proteins. Here we discuss recent studies that go beyond the traditional use of
      HDAC inhibitors and have begun to dissect the roles of individual HDAC isoforms
      in neuronal development and repair after injury. 

PMID- 24727245
TI  - Signaling regulations of neuronal regenerative ability.
AB  - Different from physiological axon growth during development, a major limiting
      factor for successful axon regeneration is the poor intrinsic regenerative
      capacity in mature neurons in the adult mammalian central nervous system (CNS).
      Recent studies identified several molecular pathways, including PTEN/mTOR,
      Jak/STAT, DLK/JNK, providing important probes in investigating the mechanisms by
      which the regenerative ability is regulated. This review will summarize these
      recent findings and speculate their implications. 

PMID- 24727246
TI  - Rab'ing tumor cell migration and invasion: focal adhesion disassembly driven by
      Rab5.
AB  - The small GTPase Rab5 has been extensively studied in the context of endocytic
      trafficking because it is critical in the regulation of early endosome dynamics.
      In addition to this canonical role, evidence obtained in recent years implicates
      Rab5 in the regulation of cell migration. This novel role of Rab5 is based not
      only on an indirect relationship between cell migration and endosomal trafficking
      as separate processes, but also on the direct regulation of signaling proteins
      implicated in cell migration. However, the precise mechanisms underlying this
      connection have remained elusive. Recent studies have shown that the activation
      of Rab5 is a critical event for maintaining the dynamics of focal adhesions,
      which is fundamental in regulating not only cell migration but also tumor cell
      invasion. 

PMID- 24727247
TI  - The Multifunctional Protein Kinase C-epsilon in Cancer Development and
      Progression.
AB  - The protein kinase C (PKC) family proteins are important signal transducers and
      have long been the focus of cancer research. PKCE, a member of this family, is
      overexpressed in most solid tumors and plays critical roles in different
      processes that lead to cancer development. Studies using cell lines and animal
      models demonstrated the transforming potential of PKCE. While earlier research
      established the survival functions of PKCE, recent studies revealed its role in
      cell migration, invasion and cancer metastasis. PKCE has also been implicated in
      epithelial to mesenchymal transition (EMT), which may be the underlying mechanism
      by which it contributes to cell motility. In addition, PKCE affects cell
      extracellular matrix (ECM) interactions by direct regulation of the cytoskeletal
      elements. Recent studies have also linked PKCE signaling to cancer stem cell
      functioning. This review focuses on the role of PKCE in different processes that
      lead to cancer development and progression. We also discussed current literatures
      on the pursuit of PKCE as a target for cancer therapy. 

PMID- 24727249
TI  - Appropriateness of primary prevention implantable cardioverter-defibrillators at
      the time of generator replacement: are indications still met?
AB  - OBJECTIVES: This study sought to determine how often patients with primary
      prevention implantable cardioverter-defibrillators (ICDs) meet guideline-derived
      indications at the time of generator replacement. BACKGROUND: Professional
      societies have developed guideline criteria for the appropriate implantation of
      an ICD for the primary prevention of sudden cardiac death. It is unknown whether
      patients continue to meet criteria when their devices need replacement for
      battery depletion. METHODS: We performed a retrospective chart review of patients
      undergoing replacement of primary prevention ICDs at 2 tertiary Veterans Affairs
      Medical Centers. Indications for continued ICD therapy at the time of generator
      replacement included a left ventricular ejection fraction (LVEF) <=35% or receipt
      of appropriate device therapy. RESULTS: In our cohort of 231 patients, 59 (26%)
      no longer met guideline-driven indications for an ICD at the time of generator
      replacement. An additional 79 patients (34%) had not received any appropriate ICD
      therapies and had not undergone reassessment of their LVEF. Patients with an
      initial LVEF of 30% to 35% were less likely to meet indications for ICD therapy
      at the time of replacement (odds ratio: 0.52; 95% confidence interval: 0.30 to
      0.88; p = 0.01). Patients without ICD indications subsequently received
      appropriate ICD therapies at a significantly lower rate than patients with
      indications (2.8% vs. 10.7% annually, p < 0.001). If ICD generator explantations
      were performed instead of replacements in the patients without ICD indications,
      the cost savings would be $1.6 million. CONCLUSIONS: Approximately 25% of
      patients who receive primary prevention ICDs may no longer meet guideline
      indications for ICD use at the time of generator replacement, and these patients
      receive subsequent ICD therapies at a significantly lower rate.

PMID- 24727248
TI  - Heterosynaptic plasticity: multiple mechanisms and multiple roles.
AB  - Plasticity is a universal property of synapses. It is expressed in a variety of
      forms mediated by a multitude of mechanisms. Here we consider two broad kinds of
      plasticity that differ in their requirement for presynaptic activity during the
      induction. Homosynaptic plasticity occurs at synapses that were active during the
      induction. It is also called input specific or associative, and it is governed by
      Hebbian-type learning rules. Heterosynaptic plasticity can be induced by episodes
      of strong postsynaptic activity also at synapses that were not active during the
      induction, thus making any synapse at a cell a target to heterosynaptic changes.
      Both forms can be induced by typical protocols used for plasticity induction and
      operate on the same time scales but have differential computational properties
      and play different roles in learning systems. Homosynaptic plasticity mediates
      associative modifications of synaptic weights. Heterosynaptic plasticity
      counteracts runaway dynamics introduced by Hebbian-type rules and balances
      synaptic changes. It provides learning systems with stability and enhances
      synaptic competition. We conclude that homosynaptic and heterosynaptic plasticity
      represent complementary properties of modifiable synapses, and both are necessary
      for normal operation of neural systems with plastic synapses. 

PMID- 24727250
TI  - Safety of dronedarone in routine clinical care.
AB  - OBJECTIVES: The aim of this study was to examine mortality and liver disease
      among patients exposed to dronedarone. BACKGROUND: There has been concern about
      the safety of dronedarone, especially for patients with heart failure and
      permanent atrial fibrillation (AF). There have also been suspicions about liver
      toxicity. METHODS: All 174,995 patients with a diagnosis of AF during 2010 to
      2012 were identified in the Swedish Patient Register. Of these, 4,856 patients
      had received dronedarone according to the Swedish Drug Register, and 170,139
      patients who had not were used as a control population. Mean follow-up was 1.6
      years, with a minimal follow-up of 6 months. RESULTS: Patients prescribed
      dronedarone were younger (age 65.5 years vs. 75.7 years, p < 0.0001) and
      healthier than control patients. The annual mortality rate among patients who
      received dronedarone was 1.3% compared with 14.0% in the control population.
      There were no sudden cardiac deaths and no deaths related to liver failure among
      patients who received treatment with dronedarone. After propensity score matching
      and adjustment for cofactors, patients who received dronedarone had lower
      mortality than other AF patients (hazard ratio [HR]: 0.41; 95% confidence
      interval [CI]: 0.33 to 0.51). Dronedarone patients with heart failure had lower
      mortality than other heart failure patients (HR: 0.40; 95% CI: 0.30 to 0.53).
      They also had lower mortality than expected from the general population
      (standardized mortality ratio: 0.67; 95% CI: 0.55 to 0.78), which indicates the
      selection of low-risk patients. The risk of liver disease was not increased (HR:
      0.57; 95% CI: 0.34 to 0.92). CONCLUSIONS: Dronedarone, as prescribed to AF
      patients in Sweden, has not exposed patients to increased risks of death or liver
      disease.

PMID- 24727251
TI  - Is it time for a new approach to implantable cardioverter-defibrillator
      replacement?

PMID- 24727252
TI  - Dronedarone: "real-world" data vis-a-vis data from randomized clinical trials.

PMID- 24727253
TI  - Reply: Cardiac positron emission tomography as a prognostic indicator of cardiac
      sarcoidosis.

PMID- 24727255
TI  - Cardiac positron emission tomography as a prognostic indicator of cardiac
      sarcoidosis.

PMID- 24727256
TI  - Benefits of statins in healthy elderly subjects: what is the number needed to
      treat?

PMID- 24727254
TI  - Fibroblast growth factor-23, cardiovascular prognosis, and benefit of angiotensin
      converting enzyme inhibition in stable ischemic heart disease.
AB  - OBJECTIVES: This study sought to test 2 hypotheses: 1) fibroblast growth factor
      (FGF)-23 identifies patients with stable ischemic heart disease (SIHD) at high
      risk of cardiovascular events independent of clinical factors, renal function,
      and established cardiovascular biomarkers; and 2) FGF-23 identifies patients who
      derive greater clinical benefit from angiotensin-converting enzyme inhibitor
      therapy. BACKGROUND: FGF-23 is an endocrine regulator of mineral metabolism and
      markedly elevated levels are associated with cardiovascular events in patients
      with chronic kidney disease. Data in patients with SIHD are more sparse. METHODS:
      FGF-23 levels were measured in 3,627 patients with SIHD randomly assigned to
      trandolapril or placebo within the PEACE (Prevention of Events With Angiotensin
      Converting Enzyme) trial and followed up for a median of 5.1 years. RESULTS:
      After adjustment for clinical risk predictors, left ventricular ejection
      fraction, markers of renal function, and established cardiovascular biomarkers,
      FGF-23 concentration was independently associated with an increased risk of
      cardiovascular death or heart failure among patients allocated to placebo
      (quartile 4 hazard ratio: 1.73; 95% confidence interval, 1.09 to 2.74; p = 0.02)
      and significantly improved metrics of discrimination. Furthermore, among patients
      in the top quartile of FGF-23 levels, trandolapril significantly reduced
      cardiovascular death or incident heart failure (hazard ratio: 0.45; 95%
      confidence interval: 0.28 to 0.72), whereas there was no clinical benefit in the
      remaining patients (hazard ratio: 1.07; 95% confidence interval: 0.75 to 1.52; p
      interaction = 0.0039). This interaction was independent of and additive to
      stratification based on renal function. CONCLUSIONS: Elevated levels of FGF-23
      are associated with cardiovascular death and incident heart failure in patients
      with SIHD and identify patients who derive significant clinical benefit from
      angiotensin-converting enzyme inhibitor therapy regardless of renal function.
      (Prevention of Events With Angiotensin-Converting Enzyme Inhibitor Therapy
      [PEACE]: NCT00000558).

PMID- 24727257
TI  - Reply: benefits of statins in healthy elderly subjects: what is the number needed
      to treat?

PMID- 24727258
TI  - Use of the 6-min walk distance to identify variations in treatment benefits from
      implantable cardioverter-defibrillator and amiodarone: results from the SCD-HeFT
      (Sudden Cardiac Death in Heart Failure Trial).
AB  - OBJECTIVES: The purpose of this study was to determine if 6-min walk test data
      assists in treatment decisions for patients with heart failure. BACKGROUND: In
      the SCD-HeFT (Sudden Cardiac Death in Heart Failure Trial), a pre-specified
      subgroup analysis showed that patients with New York Heart Association functional
      class III symptoms did not benefit from implantable cardioverter-defibrillator
      (ICD) therapy and appeared to be harmed by amiodarone, whereas New York Heart
      Association functional class II patients obtained significant survival benefit
      from ICD. We postulated that a more objective measure of functional capacity,
      such as 6-min walk (6MW) distance, might provide a better tool for selecting
      these preventive therapies. METHODS: A 6MW test was performed before
      randomization in 2,397 patients. Median follow-up was 45.5 months. All-cause
      mortality was the primary endpoint, with cause-specific mortality (heart failure,
      arrhythmic) examined in secondary analyses. RESULTS: The hazard ratios (HRs) for
      ICD therapy compared to placebo were estimated within tertiles of baseline 6MW
      distance: HR: 0.42 (95% confidence interval [CI]: 0.26 to 0.66) for 6MW distance
      >386 m (top tertile); HR: 0.57 (95% CI: 0.39 to 0.83) for 6MW distance 288 to 386
      m (middle tertile); and HR: 1.02 (95% CI: 0.75 to 1.39) for 6MW distance <288 m
      (bottom tertile). The corresponding HRs for amiodarone compared to placebo were
      0.68 (95% CI: 0.46 to 1.02) for the top, 0.86 (95% CI: 0.61 to 1.21) for the
      middle, and 1.56 (95% CI: 1.17 to 2.09) for the bottom tertile. The 6MW distance
      was inversely related to heart failure-related mortality but not to arrhythmic
      mortality. ICD therapy reduced arrhythmic mortality in the top 2 tertiles of 6MW,
      but had no effect on heart failure mortality. CONCLUSIONS: A baseline 6MW
      distance <288 m identified a subgroup of SCD-HeFT patients who were harmed by
      amiodarone therapy and did not benefit from ICD. (Sudden Cardiac Death in Heart
      Failure Trial [SCD-HeFT]; NCT00000609).

PMID- 24727259
TI  - Strabismus in childhood eyelid ptosis.
AB  - PURPOSE: To report the prevalence and causes of strabismus in children with
      eyelid ptosis diagnosed in a well-defined population over a 40-year period.
      DESIGN: Retrospective, population-based cohort study. METHODS: We retrospectively
      reviewed the charts of 107 patients (<19 years) for the prevalence and causes of
      strabismus in children who were diagnosed with childhood eyelid ptosis as
      residents of Olmsted County, Minnesota, from January 1, 1965, through December
      31, 2004. RESULTS: Strabismus was diagnosed in 20 (18.7%) of the 107 patients
      with childhood ptosis. Of the 81 patients, 8 (9.9%) were diagnosed with simple
      congenital ptosis and had strabismus, of which there were 4 (4.9%) cases of
      exotropia and 4 (4.9%) cases of esotropia. There were no cases of isolated
      vertical deviation. CONCLUSIONS: Strabismus occurred in 1 of 5 children diagnosed
      with any form of childhood ptosis in this population-based cohort. Strabismus
      affected approximately 1 of 10 patients diagnosed with simple congenital ptosis,
      and a predominance of isolated horizontal deviations was equally divided between
      esotropia and exotropia.

PMID- 24727260
TI  - Choroidal changes associated with Bruch membrane pathology in pseudoxanthoma
      elasticum.
AB  - PURPOSE: To investigate the impact of Bruch membrane pathology on the choroid in
      pseudoxanthoma elasticum (PXE). DESIGN: Monocenter cross-sectional prospective
      case series. METHODS: The study included 61 eyes of 51 patients with PXE and 54
      eyes of 54 normal subjects. The diagnosis of PXE was based on skin biopsy,
      genetic analysis or both. Eyes with PXE were subdivided into 3 groups: eyes
      without choroidal neovascularization (CNV) or chorioretinal atrophy (Group 1);
      eyes with active or fibrotic CNV (Group 2); and eyes with chorioretinal atrophy
      only (Group 3). Choroidal thickness was measured using enhanced-depth imaging
      optical coherence tomography (EDI-OCT). RESULTS: Compared to controls (331 MUm +/
      24; mean +/- 95% CI), mean subfoveal choroidal thickness in eyes of patients
      with PXE was significantly reduced within all 3 groups (Group 1: 243 MUm +/- 29;
      Group 2: 184 MUm +/- 28; Group 3: 104 MUm +/- 28; P < 0.001). Associated
      structural changes included apparent loss of small choroidal vessels. The
      difference of PXE compared to control eyes was largest close to the optic disc
      and approximated the level of controls toward the periphery. Within the PXE
      subgroups, eyes without CNV or chorioretinal atrophy (Group 1) showed the least
      reduction of choroidal thickness, while it was most pronounced in Group 3.
      CONCLUSIONS: The results indicate that changes of Bruch membrane can be
      associated with choroidal alterations, which are most pronounced in the presence
      of advanced disease. A role of Bruch membrane in choroidal homeostasis may
      reflect a possible contribution of Bruch membrane alterations to CNV and
      geographic atrophy development in age-related macular degeneration.

PMID- 24727262
TI  - Visual field improvement in the collaborative initial glaucoma treatment study.
AB  - PURPOSE: To evaluate critically visual field (VF) improvement in participants in
      the Collaborative Initial Glaucoma Treatment Study (CIGTS). DESIGN: Prospective,
      comparative case series from a randomized clinical trial comparing trabeculectomy
      and topical medications in treating open-angle glaucoma (OAG). METHODS: A total
      of 607 subjects with newly diagnosed OAG were identified for study. Baseline and
      follow-up VF tests were obtained and mean deviation (MD) change from baseline
      over follow-up was analyzed. Clinically substantial change (loss or improvement)
      was defined as change from baseline of >= 3 decibels in MD. Baseline factors were
      inspected to determine their association with VF improvement in repeated measures
      regression models. RESULTS: The percentage of participants showing substantial VF
      improvement over time was similar to that showing VF loss through 5 years after
      initial treatment, after which VF loss became more frequent. Measures of better
      intraocular pressure (IOP) control during treatment were significantly predictive
      of VF improvement, including a lower mean IOP, a lower minimum IOP, and lower
      sustained levels of IOP over follow-up. Other predictive factors included female
      sex (odds ratio [OR] = 1.73), visits 1 year prior to cataract extraction (OR =
      0.11), and an interaction between treatment and baseline MD wherein surgically
      treated subjects with worse baseline VF loss were more likely to show VF
      improvement. CONCLUSIONS: In the CIGTS, substantial VF loss and improvement were
      comparable through 5 years of follow-up, after which VF loss became more
      frequent. Predictive factors for VF improvement included several indicators of
      better IOP control, which supports the postulate that VF improvement was real.

PMID- 24727263
TI  - Association between the percent tissue altered and post-laser in situ
      keratomileusis ectasia in eyes with normal preoperative topography.
AB  - PURPOSE: To investigate the association of a novel metric, percent tissue
      altered, with the occurrence of ectasia after laser in situ keratomileusis
      (LASIK) in eyes with normal corneal topography and to compare this metric with
      other recognized risk factors. DESIGN: Retrospective case-control study. METHODS:
      The study included 30 eyes from 16 patients with bilateral normal preoperative
      Placido-based corneal topography that developed ectasia after LASIK (ectasia
      group) and 174 eyes from 88 consecutive patients with uncomplicated LASIK and at
      least 3 years of postoperative follow-up. The following metrics were evaluated:
      age, preoperative central corneal thickness, residual stromal bed, Ectasia Risk
      Score System scores, and percent tissue altered, derived from [PTA = (FT +
      AD)/CCT], where FT = flap thickness, AD = ablation depth, and CCT = preoperative
      central corneal thickness. RESULTS: In the ectasia group, percent tissue altered
      >=40 was the most prevalent factor (97%), followed by age <30 years (63%),
      residual stromal bed <=300 MUm (57%), and ectasia risk score >= 3 (43%) (P < .001
      for all). Percent tissue altered >= 40 had the highest odds ratio (223), followed
      by residual stromal bed <= 300 MUm (74) and ectasia risk score >= 4 (8). Stepwise
      logistic regression revealed percent tissue altered >= 40 as the single most
      significant independent variable (P < .0001). CONCLUSIONS: Percent tissue altered
      at the time of LASIK was significantly associated with the development of ectasia
      in eyes with normal preoperative topography and was a more robust indicator of
      risk than all other variables in this patient population.

PMID- 24727264
TI  - VCMM: a visual tool for continuum molecular modeling.
AB  - This paper describes the design and function of a visualization tool, VCMM, for
      visualizing and analyzing data, and interfacing solvers for generic continuum
      molecular modeling. In particular, an emphasis of the program is to treat the
      data set based on unstructured mesh as used in finite/boundary element
      simulations, which largely enhances the capabilities of current visualization
      tools in this area that only support structured mesh. VCMM is segmented into
      molecular, meshing and numerical modules. The capabilities of molecular module
      include molecular visualization and force field assignment. Meshing module
      contains mesh generation, analysis and visualization tools. Numerical module
      currently provides a few finite/boundary element solvers of continuum molecular
      modeling, and contains several common visualization tools for the numerical
      result such as line and plane interpolations, surface probing, volume rendering
      and stream rendering. Three modules can exchange data with each other and carry
      out a complete process of modeling. Interfaces are also designed in order to
      facilitate usage of other mesh generation tools and numerical solvers. We develop
      a technique to accelerate data retrieval and have combined many graphical
      techniques in visualization. VCMM is highly extensible, and users can obtain more
      powerful functions by introducing relevant plug-ins. VCMM can also be useful in
      other fields such as computational quantum chemistry, image processing, and
      material science.

PMID- 24727265
TI  - Impact of UV and peracetic acid disinfection on the prevalence of virulence and
      antimicrobial resistance genes in uropathogenic Escherichia coli in wastewater
      effluents.
AB  - Wastewater discharges may increase the populations of pathogens, including
      Escherichia coli, and of antimicrobial-resistant strains in receiving waters.
      This study investigated the impact of UV and peracetic acid (PAA) disinfection on
      the prevalence of virulence and antimicrobial resistance genes in uropathogenic
      Escherichia coli (UPEC), the most abundant E. coli pathotype in municipal
      wastewaters. Laboratory disinfection experiments were conducted on wastewater
      treated by physicochemical, activated sludge, or biofiltration processes; 1,766
      E. coli isolates were obtained for the evaluation. The target disinfection level
      was 200 CFU/100 ml, resulting in UV and PAA doses of 7 to 30 mJ/cm(2) and 0.9 to
      2.0 mg/liter, respectively. The proportions of UPECs were reduced in all samples
      after disinfection, with an average reduction by UV of 55% (range, 22% to 80%)
      and by PAA of 52% (range, 11% to 100%). Analysis of urovirulence genes revealed
      that the decline in the UPEC populations was not associated with any particular
      virulence factor. A positive association was found between the occurrence of
      urovirulence and antimicrobial resistance genes (ARGs). However, the changes in
      the prevalence of ARGs in potential UPECs were different following disinfection,
      i.e., UV appears to have had no effect, while PAA significantly reduced the ARG
      levels. Thus, this study showed that both UV and PAA disinfections reduced the
      proportion of UPECs and that PAA disinfection also reduced the proportion of
      antimicrobial resistance gene-carrying UPEC pathotypes in municipal wastewaters.

PMID- 24727266
TI  - Fluorescence-based quasicontinuous and in situ monitoring of biofilm formation
      dynamics in natural marine environments.
AB  - Analyzing the dynamics of biofilm formation helps to deepen our understanding of
      surface colonization in natural environments. While methods for screening biofilm
      formation in the laboratory are well established, studies in marine environments
      have so far been based upon destructive analysis of individual samples and
      provide only discontinuous snapshots of biofilm establishment. In order to
      explore the development of biofilm over time and under various biotic and abiotic
      conditions, we applied a recently developed optical biofilm sensor to
      quasicontinuously analyze marine biofilm dynamics in situ. Using this technique
      in combination with microscope-assisted imaging, we investigated biofilm
      formation from its beginning to mature multispecies biofilms. In contrast to
      laboratory studies on biofilm formation, a smooth transition from initial
      attachment to colony formation and exponential growth could not be observed in
      the marine environment. Instead, initial attachment was followed by an adaptation
      phase of low growth and homogeneously distributed solitary bacterial cells.
      Moreover, we observed a diurnal variation of biofilm signal intensity, suggesting
      a transient state of biofilm formation of bacteria. Overall, the biofilm
      formation dynamics could be modeled by three consecutive development stages
      attributed to initial bacterial attachment, bacterial growth, and attachment and
      growth of unicellular eukaryotic microorganisms. Additional experiments showed
      that the presence of seaweed considerably shortened the adaptation phase in
      comparison with that on control surfaces but yielded similar growth rates. The
      outlined examples highlight the advantages of a quasicontinuous in situ detection
      that enabled, for the first time, the exploration of the initial attachment phase
      and the diurnal variation during biofilm formation in natural ecosystems.

PMID- 24727267
TI  - Evolved osmotolerant Escherichia coli mutants frequently exhibit defective N
      acetylglucosamine catabolism and point mutations in cell shape-regulating protein
      MreB.
AB  - Biocatalyst robustness toward stresses imposed during fermentation is important
      for efficient bio-based production. Osmotic stress, imposed by high osmolyte
      concentrations or dense populations, can significantly impact growth and
      productivity. In order to better understand the osmotic stress tolerance
      phenotype, we evolved sexual (capable of in situ DNA exchange) and asexual
      Escherichia coli strains under sodium chloride (NaCl) stress. All isolates had
      significantly improved growth under selection and could grow in up to 0.80 M (47
      g/liter) NaCl, a concentration that completely inhibits the growth of the
      unevolved parental strains. Whole genome resequencing revealed frequent mutations
      in genes controlling N-acetylglucosamine catabolism (nagC, nagA), cell shape
      (mrdA, mreB), osmoprotectant uptake (proV), and motility (fimA). Possible
      epistatic interactions between nagC, nagA, fimA, and proV deletions were also
      detected when reconstructed as defined mutations. Biofilm formation under osmotic
      stress was found to be decreased in most mutant isolates, coupled with
      perturbations in indole secretion. Transcriptional analysis also revealed
      significant changes in ompACGL porin expression and increased transcription of
      sulfonate uptake systems in the evolved mutants. These findings expand our
      current knowledge of the osmotic stress phenotype and will be useful for the
      rational engineering of osmotic tolerance into industrial strains in the future. 

PMID- 24727268
TI  - Correlating microbial diversity patterns with geochemistry in an extreme and
      heterogeneous environment of mine tailings.
AB  - Recent molecular surveys have advanced our understanding of the forces shaping
      the large-scale ecological distribution of microbes in Earth's extreme habitats,
      such as hot springs and acid mine drainage. However, few investigations have
      attempted dense spatial analyses of specific sites to resolve the local diversity
      of these extraordinary organisms and how communities are shaped by the harsh
      environmental conditions found there. We have applied a 16S rRNA gene-targeted
      454 pyrosequencing approach to explore the phylogenetic differentiation among 90
      microbial communities from a massive copper tailing impoundment generating acidic
      drainage and coupled these variations in community composition with geochemical
      parameters to reveal ecological interactions in this extreme environment. Our
      data showed that the overall microbial diversity estimates and relative
      abundances of most of the dominant lineages were significantly correlated with
      pH, with the simplest assemblages occurring under extremely acidic conditions and
      more diverse assemblages associated with neutral pHs. The consistent shifts in
      community composition along the pH gradient indicated that different taxa were
      involved in the different acidification stages of the mine tailings. Moreover,
      the effect of pH in shaping phylogenetic structure within specific lineages was
      also clearly evident, although the phylogenetic differentiations within the
      Alphaproteobacteria, Deltaproteobacteria, and Firmicutes were attributed to
      variations in ferric and ferrous iron concentrations. Application of the
      microbial assemblage prediction model further supported pH as the major factor
      driving community structure and demonstrated that several of the major lineages
      are readily predictable. Together, these results suggest that pH is primarily
      responsible for structuring whole communities in the extreme and heterogeneous
      mine tailings, although the diverse microbial taxa may respond differently to
      various environmental conditions.

PMID- 24727269
TI  - In situ analysis of metabolic characteristics reveals the key yeast in the
      spontaneous and solid-state fermentation process of Chinese light-style liquor.
AB  - The in situ metabolic characteristics of the yeasts involved in spontaneous
      fermentation process of Chinese light-style liquor are poorly understood. The
      covariation between metabolic profiles and yeast communities in Chinese light
      style liquor was modeled using the partial least square (PLS) regression method.
      The diversity of yeast species was evaluated by sequence analysis of the 26S
      ribosomal DNA (rDNA) D1/D2 domains of cultivable yeasts, and the volatile
      compounds in fermented grains were analyzed by gas chromatography (GC)-mass
      spectrometry (MS). Eight yeast species and 58 volatile compounds were identified,
      respectively. The modulation of 16 of these volatile compounds was associated
      with variations in the yeast population (goodness of prediction [Q(2)]>20%). The
      results showed that Pichia anomala was responsible for the characteristic aroma
      of Chinese liquor, through the regulation of several important volatile
      compounds, such as ethyl lactate, octanoic acid, and ethyl tetradecanoate.
      Correspondingly, almost all of the compounds associated with P. anomala were
      detected in a pure culture of this yeast. In contrast to the PLS regression
      results, however, ethyl lactate and ethyl isobutyrate were not detected in the
      same pure culture, which indicated that some metabolites could be generated by P.
      anomala only when it existed in a community with other yeast species.
      Furthermore, different yeast communities provided different volatile patterns in
      the fermented grains, which resulted in distinct flavor profiles in the resulting
      liquors. This study could help identify the key yeast species involved in
      spontaneous fermentation and provide a deeper understanding of the role of
      individual yeast species in the community.

PMID- 24727270
TI  - High prevalence of Enterocytozoon bieneusi in asymptomatic pigs and assessment of
      zoonotic risk at the genotype level.
AB  - Enterocytozoon bieneusi is an emerging and clinically significant enteric
      parasite infecting humans and animals and can cause life-threatening diarrhea in
      immunocompromised people. Pigs are considered to be one of the main reservoir
      hosts of E. bieneusi based on their high prevalence rates and zoonotic genotypes
      in pigs. As an opportunistic pathogen, E. bieneusi infection of pigs can be
      inapparent, which leads to neglect in detecting this parasite in pigs and
      assessing the epidemiological role of pigs in the transmission of human
      microsporidiosis. In the present study, 95 healthy pigs aged 2 or 3 months were
      randomly selected from three areas in Heilongjiang Province, China. E. bieneusi
      isolates were identified and genotyped based on the small-subunit (SSU) rRNA and
      internal transcribed spacer (ITS) regions of the rRNA gene by PCR and sequencing.
      A high prevalence of E. bieneusi was observed, 83.2% (79/95) at the SSU rRNA
      locus versus 89.5% (85/95) at the ITS locus. Ten ITS genotypes were obtained,
      comprising six known genotypes-EbpA (n = 30), D (n = 19), H (n = 18), O (n = 11),
      CS-1 (n = 1), and LW1 (n = 1)-and four novel genotypes named HLJ-I to HLJ-IV;
      70.6% (60/85) of E. bieneusi genotypes were zoonotic (genotypes EbpA, D, and O).
      The findings of a high prevalence of E. bieneusi in pigs and a large percentage
      of zoonotic genotypes indicate that pigs may play a role in the transmission of
      E. bieneusi to humans and may become an important source of water contamination
      in our investigated areas.

PMID- 24727271
TI  - Verrucomicrobia are candidates for polysaccharide-degrading bacterioplankton in
      an arctic fjord of Svalbard.
AB  - In Arctic marine bacterial communities, members of the phylum Verrucomicrobia are
      consistently detected, although not typically abundant, in 16S rRNA gene clone
      libraries and pyrotag surveys of the marine water column and in sediments. In an
      Arctic fjord (Smeerenburgfjord) of Svalbard, members of the Verrucomicrobia,
      together with Flavobacteria and smaller proportions of Alpha- and
      Gammaproteobacteria, constituted the most frequently detected bacterioplankton
      community members in 16S rRNA gene-based clone library analyses of the water
      column. Parallel measurements in the water column of the activities of six endo
      acting polysaccharide hydrolases showed that chondroitin sulfate, laminarin, and
      xylan hydrolysis accounted for most of the activity. Several Verrucomicrobia
      water column phylotypes were affiliated with previously sequenced, glycoside
      hydrolase-rich genomes of individual Verrucomicrobia cells that bound
      fluorescently labeled laminarin and xylan and therefore constituted candidates
      for laminarin and xylan hydrolysis. In sediments, the bacterial community was
      dominated by different lineages of Verrucomicrobia, Bacteroidetes, and
      Proteobacteria but also included members of multiple phylum-level lineages not
      observed in the water column. This community hydrolyzed laminarin, xylan,
      chondroitin sulfate, and three additional polysaccharide substrates at high
      rates. Comparisons with data from the same fjord in the previous summer showed
      that the bacterial community in Smeerenburgfjord changed in composition, most
      conspicuously in the changing detection frequency of Verrucomicrobia in the water
      column. Nonetheless, in both years the community hydrolyzed the same
      polysaccharide substrates.

PMID- 24727272
TI  - Development and evaluation of a novel multicopy-element-targeting triplex PCR for
      detection of Mycobacterium avium subsp. paratuberculosis in feces.
AB  - The enteropathy called paratuberculosis (PTB), which mainly affects ruminants and
      has a worldwide distribution, is caused by Mycobacterium avium subsp.
      paratuberculosis. This disease significantly reduces the cost-effectiveness of
      ruminant farms, and therefore, reliable and rapid detection methods are needed to
      control the spread of the bacterium in livestock and in the environment. The aim
      of this study was to identify a specific and sensitive combination of DNA
      extraction and amplification to detect M. avium subsp. paratuberculosis in feces.
      Negative bovine fecal samples were inoculated with increasing concentrations of
      two different bacterial strains (field and reference) to compare the performance
      of four extraction and five amplification protocols. The best results were
      obtained using the JohnePrep and MagMax extraction kits combined with an in-house
      triplex real-time PCR designed to detect IS900, ISMap02 (an insertion sequence of
      M. avium subsp. paratuberculosis present in 6 copies per genome), and an internal
      amplification control DNA simultaneously. These combinations detected 10 M. avium
      subsp. paratuberculosis cells/g of spiked feces. The triplex PCR detected 1 fg of
      genomic DNA extracted from the reference strain K10. The performance of the
      robotized version of the MagMax extraction kit combined with the IS900 and
      ISMap02 PCR was further evaluated using 615 archival fecal samples from the first
      sampling of nine Friesian cattle herds included in a PTB control program and
      followed up for at least 4 years. The analysis of the results obtained in this
      survey demonstrated that the diagnostic method was highly specific and sensitive
      for the detection of M. avium subsp. paratuberculosis in fecal samples from
      cattle and a very valuable tool to be used in PTB control programs.

PMID- 24727273
TI  - Brine assemblages of ultrasmall microbial cells within the ice cover of Lake
      Vida, Antarctica.
AB  - The anoxic and freezing brine that permeates Lake Vida's perennial ice below 16 m
      contains an abundance of very small (<=0.2-MUm) particles mixed with a less
      abundant population of microbial cells ranging from >0.2 to 1.5 MUm in length.
      Fluorescent DNA staining, electron microscopy (EM) observations, elemental
      analysis, and extraction of high-molecular-weight genomic DNA indicated that a
      significant portion of these ultrasmall particles are cells. A continuous
      electron-dense layer surrounding a less electron-dense region was observed by EM,
      indicating the presence of a biological membrane surrounding a cytoplasm. The
      ultrasmall cells are 0.192 +/- 0.065 MUm, with morphology characteristic of
      coccoid and diplococcic bacterial cells, often surrounded by iron-rich capsular
      structures. EM observations also detected the presence of smaller unidentified
      nanoparticles of 0.020 to 0.140 MUm among the brine cells. A 16S rRNA gene clone
      library from the brine 0.1- to 0.2-MUm-size fraction revealed a relatively low
      diversity assemblage of Bacteria sequences distinct from the previously reported
      >0.2-MUm-cell-size Lake Vida brine assemblage. The brine 0.1- to 0.2-MUm-size
      fraction was dominated by the Proteobacteria-affiliated genera Herbaspirillum,
      Pseudoalteromonas, and Marinobacter. Cultivation efforts of the 0.1- to 0.2-MUm
      size fraction led to the isolation of Actinobacteria-affiliated genera
      Microbacterium and Kocuria. Based on phylogenetic relatedness and microscopic
      observations, we hypothesize that the ultrasmall cells in Lake Vida brine are
      ultramicrocells that are likely in a reduced size state as a result of
      environmental stress or life cycle-related conditions.

PMID- 24727274
TI  - Long-term monitoring of waterborne pathogens and microbial source tracking
      markers in paired agricultural watersheds under controlled and conventional tile
      drainage management.
AB  - Surface waters from paired agricultural watersheds under controlled tile drainage
      (CTD) and uncontrolled tile drainage (UCTD) were monitored over 7 years in order
      to determine if there was an effect of CTD (imposed during the growing season) on
      occurrences and loadings of bacterial and viral pathogens, coliphages, and
      microbial source tracking markers. There were significantly lower occurrences of
      human, ruminant, and livestock (ruminant plus pig) Bacteroidales markers in the
      CTD watershed in relation to the UCTD watershed. As for pathogens, there were
      significantly lower occurrences of Salmonella spp. and Arcobacter spp. in the CTD
      watershed. There were no instances where there were significantly higher
      quantitative loadings of any microbial target in the CTD watershed, except for F
      specific DNA (F-DNA) and F-RNA coliphages, perhaps as a result of fecal inputs
      from a hobby farm independent of the drainage practice treatments. There was
      lower loading of the ruminant marker in the CTD watershed in relation to the UCTD
      system, and results were significant at the level P = 0.06. The odds of
      Salmonella spp. occurring increased when a ruminant marker was present relative
      to when the ruminant marker was absent, yet for Arcobacter spp., the odds of this
      pathogen occurring significantly decreased when a ruminant marker was present
      relative to when the ruminant marker was absent (but increased when a wildlife
      marker was present relative to when the wildlife marker was absent).
      Interestingly, the odds of norovirus GII (associated with human and swine)
      occurring in water increased significantly when a ruminant marker was present
      relative to when a ruminant marker was absent. Overall, this study suggests that
      fecal pollution from tile-drained fields to stream could be reduced by CTD
      utilization.

PMID- 24727275
TI  - Production of proteasome inhibitor syringolin A by the endophyte Rhizobium sp.
      strain AP16.
AB  - Syringolin A, the product of a mixed nonribosomal peptide synthetase/polyketide
      synthase encoded by the syl gene cluster, is a virulence factor secreted by
      certain Pseudomonas syringae strains. Together with the glidobactins produced by
      a number of beta- and gammaproteobacterial human and animal pathogens, it belongs
      to the syrbactins, a structurally novel class of proteasome inhibitors. In
      plants, proteasome inhibition by syringolin A-producing P. syringae strains leads
      to the suppression of host defense pathways requiring proteasome activity, such
      as the ones mediated by salicylic acid and jasmonic acid. Here we report the
      discovery of a syl-like gene cluster with some unusual features in the
      alphaproteobacterial endophyte Rhizobium sp. strain AP16 that encodes a putative
      syringolin A-like synthetase whose components share 55% to 65% sequence identity
      (72% to 79% similarity) at the amino acid level. As revealed by average
      nucleotide identity (ANI) calculations, this strain likely belongs to the same
      species as biocontrol strain R. rhizogenes K84 (formely known as Agrobacterium
      radiobacter K84), which, however, carries a nonfunctional deletion remnant of the
      syl-like gene cluster. Here we present a functional analysis of the syl-like gene
      cluster of Rhizobium sp. strain AP16 and demonstrate that this endophyte
      synthesizes syringolin A and some related minor variants, suggesting that
      proteasome inhibition by syrbactin production can be important not only for
      pathogens but also for endophytic bacteria in the interaction with their hosts.

PMID- 24727276
TI  - hypD as a marker for [NiFe]-hydrogenases in microbial communities of surface
      waters.
AB  - Hydrogen is an important trace gas in the atmosphere. Soil microorganisms are
      known to be an important part of the biogeochemical H2 cycle, contributing 80 to
      90% of the annual hydrogen uptake. Different aquatic ecosystems act as either
      sources or sinks of hydrogen, but the contribution of their microbial communities
      is unknown. [NiFe]-hydrogenases are the best candidates for hydrogen turnover in
      these environments since they are able to cope with oxygen. As they lack
      sufficiently conserved sequence motifs, reliable markers for these enzymes are
      missing, and consequently, little is known about their environmental
      distribution. We analyzed the essential maturation genes of [NiFe]-hydrogenases,
      including their frequency of horizontal gene transfer, and found hypD to be an
      applicable marker for the detection of the different known hydrogenase groups.
      Investigation of two freshwater lakes showed that [NiFe]-hydrogenases occur in
      many prokaryotic orders. We found that the respective hypD genes cooccur with
      oxygen-tolerant [NiFe]-hydrogenases (groups 1 and 5) mainly of Actinobacteria,
      Acidobacteria, and Burkholderiales; cyanobacterial uptake hydrogenases (group 2a)
      of cyanobacteria; H2-sensing hydrogenases (group 2b) of Burkholderiales,
      Rhizobiales, and Rhodobacterales; and two groups of multimeric soluble
      hydrogenases (groups 3b and 3d) of Legionellales and cyanobacteria. These
      findings support and expand a previous analysis of metagenomic data (M. Barz et
      al., PLoS One 5:e13846, 2010, http://dx.doi.org/10.1371/journal.pone.0013846) and
      further identify [NiFe]-hydrogenases that could be involved in hydrogen cycling
      in aquatic surface waters.

PMID- 24727277
TI  - Bacterial symbionts of a devastating coffee plant pest, the stinkbug Antestiopsis
      thunbergii (Hemiptera: Pentatomidae).
AB  - Stinkbugs of the genus Antestiopsis, so-called antestia bugs or variegated coffee
      bugs, are notorious pests of coffee plants in Africa. We investigated the
      symbiotic bacteria associated with Antestiopsis thunbergii, a major coffee plant
      pest in Rwanda. PCR, cloning, sequencing, and phylogenetic analysis of bacterial
      genes identified four distinct bacterial lineages associated with A. thunbergii:
      a gammaproteobacterial gut symbiont and symbionts representing the genera
      Sodalis, Spiroplasma, and Rickettsia. In situ hybridization showed that the gut
      symbiont densely occupied the lumen of midgut crypts, whereas the Sodalis
      symbiont, the Spiroplasma symbiont, and the Rickettsia symbiont sparsely and
      sporadically infected various cells and tissues. Diagnostic PCR survey of 154 A.
      thunbergii individuals collected at 8 localities in Rwanda revealed high
      infection frequencies (100% for the gut symbiont, 51.3% for the Sodalis symbiont,
      52.6% for the Spiroplasma symbiont, and 24.0% for the Rickettsia symbiont). These
      results suggest that the gut symbiont is the primary symbiotic associate of
      obligate nature for A. thunbergii, whereas the Sodalis symbiont, the Spiroplasma
      symbiont, and the Rickettsia symbiont are the secondary symbiotic associates of
      facultative nature. We observed high coinfection frequencies, i.e., 7.8% of
      individuals with quadruple infection with all the symbionts, 32.5% with triple
      infections with the gut symbiont and two of the secondary symbionts, and 39.6%
      with double infections with the gut symbiont and any of the three secondary
      symbionts, which were statistically not different from the expected coinfection
      frequencies and probably reflected random associations. The knowledge of
      symbiotic microbiota in A. thunbergii will provide useful background information
      for controlling this devastating coffee plant pest.

PMID- 24727261
TI  - Sporadic visual acuity loss in the Comparison of Age-Related Macular Degeneration
      Treatments Trials (CATT).
AB  - PURPOSE: To evaluate transient, large visual acuity (VA) decreases, termed
      sporadic vision loss, during anti-vascular endothelial growth factor treatment
      for neovascular age-related macular degeneration (AMD). DESIGN: Cohort within a
      randomized clinical trial. METHODS: setting: Comparison of Age-Related Macular
      Degeneration Treatments Trials (CATT). study population: Total of 1185 CATT
      patients. main outcome measures: Incidence of sporadic vision loss and odds ratio
      (OR) for association with patient and ocular factors. Sporadic vision loss was a
      decline of >=15 letters from the previous visit, followed by a return at the next
      visit to no more than 5 letters worse than the visit before the VA loss. RESULTS:
      There were 143 sporadic vision loss events in 122 of 1185 patients (10.3%). Mean
      VA at 2 years for those with and without sporadic vision loss was 58.5 (~20/63)
      and 68.4 (~20/40) letters, respectively (P < .001). Among patients treated pro re
      nata, no injection was given for 27.6% (27/98) of sporadic vision loss events.
      Multivariate analysis demonstrated that baseline predictors for sporadic vision
      loss included worse baseline VA (OR 2.92, 95% confidence interval [CI]:1.65-5.17
      for <=20/200 compared with >=20/40), scar (OR 2.21, 95% CI:1.22-4.01),
      intraretinal foveal fluid on optical coherence tomography (OR 1.80, 95% CI:1.11
      2.91), and medical history of anxiety (OR 1.90, 95% CI:1.12-3.24) and syncope (OR
      2.75, 95% CI:1.45-5.22). Refraction decreased the likelihood of sporadic vision
      loss (OR 0.62, 95%CI: 0.42-0.91). CONCLUSIONS: Approximately 10% of CATT patients
      had sporadic vision loss. Baseline predictors included AMD-related factors and
      factors independent of AMD. These data are relevant for clinicians in practice
      and those involved in clinical trials.

PMID- 24727279
TI  - Molecular design and synthesis of 1,4-disubstituted piperazines as alpha(1)
      adrenergic receptor blockers.
AB  - A new series of 4,5,6,7-tetrahydrothieno[2,3-c]pyridine-3-carboxylic acid amide
      and 3,5,6,8-tetrahydropyrido[4',3':4,5]thieno[2,3-d]pyrimidin-4-one derivatives
      were designed, synthesized, their binding and functional properties as alpha1
      adrenoreceptors blockers were evaluated. A new validated alpha1-adrenoreceptor
      blocker pharmacophore model (hypothesis) was generated using Discovery Studio
      2.5. The compare-fit study for the designed molecules with the generated
      hypothesis was fulfilled and several compounds showed significant high fit
      values. Compounds IVa-c, VIIa-d, VIIIa-c, Xa-c, XIa-d have shown blocking
      activity ranging from 46.73% up to 94.74% compared to 99.17% for prazosin. 

PMID- 24727278
TI  - Trends in medical use, diversion, and nonmedical use of prescription medications
      among college students from 2003 to 2013: Connecting the dots.
AB  - OBJECTIVES: To examine trends in the lifetime and past-year prevalence of medical
      use, diversion, and nonmedical use of four prescription medication classes (i.e.,
      sedative/anxiety, opioid, sleeping, and stimulant) among college students between
      2003 and 2013; and to identify demographic and background characteristics
      associated with trends in past-year nonmedical use of prescription medications.
      METHODS: A self-administered, cross-sectional Web survey was conducted in 2003,
      2005, 2007, 2009, 2011, and 2013 at a large public four-year university in the
      Midwest United States. RESULTS: Approximately one in every five individuals
      reported nonmedical use of at least one prescription medication class in their
      lifetime. The past-year prevalence of medical use, diversion and nonmedical use
      of prescription stimulants increased significantly between 2003 and 2013 while
      the past-year prevalence of medical use, diversion and nonmedical use of
      prescription opioids decreased significantly over this same time period. The odds
      of past-year nonmedical use of each prescription medication class were generally
      greater among males, Whites, members of social fraternities and sororities, and
      those with a lifetime history of medical use of prescription medications or a
      past-year history of being approached to divert their prescription medications.
      CONCLUSIONS: The present study represents the first investigation to demonstrate
      that trends in medical use of controlled medications parallel changes in
      diversion and nonmedical use of the same medication class among college students.
      The findings reinforce the importance of continued monitoring of prescription
      medication use at colleges to help guide prevention and intervention efforts.

PMID- 24727280
TI  - Reactor performance of a 750 m(3) anaerobic digestion plant: varied substrate
      input conditions impacting methanogenic community.
AB  - A 750 m(3) anaerobic digester was studied over a half year period including a
      shift from good reactor performance to a reduced one. Various abiotic parameters
      like volatile fatty acids (VFA) (formic-, acetic-, propionic-, (iso-)butyric-,
      (iso-)valeric-, lactic acid), total C, total N, NH4 -N, and total proteins, as
      well as the organic matter content and dry mass were determined. In addition
      several process parameters such as temperature, pH, retention time and input of
      substrate and the concentrations of CH4, H2, CO2 and H2S within the reactor were
      monitored continuously. The present study aimed at the investigation of the
      abundance of acetogens and total cell numbers and the microbial methanogenic
      community as derived from PCR-dHPLC analysis in order to put it into context with
      the determined abiotic parameters. An influence of substrate quantity on the
      efficiency of the anaerobic digestion process was found as well as a shift from a
      hydrogenotrophic in times of good reactor performance towards an acetoclastic
      dominated methanogenic community in times of reduced reactor performance. After
      the change in substrate conditions it took the methano-archaeal community about 5
      6 weeks to be affected but then changes occurred quickly. 

PMID- 24727281
TI  - Investigation of a new core-shell particle column for ion-pair reversed-phase
      liquid chromatography analysis of oligonucleotides.
AB  - A new core-shell particle column showed excellent performance and durability for
      separation of short (~21-mer) ribonucleic acid (RNA) oligonucleotides by ion-pair
      reversed-phase liquid chromatography (IP-RPLC). Previously investigated core
      shell C18 columns showed excellent peak shapes and separations of closely eluting
      impurities by IP-RPLC. However, these columns showed only modest long-term
      stability at the neutral pH and elevated column temperatures of >=60 degrees C,
      typically used for IP-RPLC analysis of oligonucleotides. The newly introduced
      SunShell C18 column provided separations comparable to the previously evaluated
      core-shell columns, but with significantly improved long-term column stability
      when operated at neutral pH and elevated column temperature. 

PMID- 24727282
TI  - Investigation of active pharmaceutical ingredient loss in pharmaceutical
      compounding of capsules.
AB  - Pharmaceutical compounding of capsules is still an important corner stone in
      today's health care. It allows for a more patient specific treatment plan as
      opposed to the "one size fits all"-approach, used by the pharmaceutical industry
      when producing fixed dose finished drug products. However, loss of active
      pharmaceutical ingredient (API) powder during pharmaceutical capsule compounding
      can lead to under-dosed finished drug products and annul the beneficiary
      therapeutic effects for the patient. The amount and location of API loss was
      experimentally determined during capsule compounding of five different
      preparations: 10 and 20mg hydrocortisone capsules, 4mg triamcinolone capsules and
      0.25mg dexamethasone capsules, using a 10% m/m self-made or commercial
      trituration. The total API amount present in the five capsule preparations varied
      between 90.8% and 96.6%, demonstrating that for certain preparations, significant
      API mass loss occurred during the pharmaceutical compounding of capsules.
      Swabbing results of the different compounding equipment and working areas
      indicated the mortar surface as the largest API loss location. An agate mortar
      accounted for the least amount of API loss, whereas an extensively used porcelain
      mortar accounted for the highest amount of API loss. Optical microscopy and
      roughness (Ra) determination by profilometry of the different mortar surfaces
      revealed a significant influence of the mortar surface wear and tear on the
      observed API loss. This observation can be explained by physical deformation, or
      scratch formation, of the relatively soft porcelain mortar surface, in which the
      API particles can become adsorbed. Furthermore, a small effect of the capsulation
      device material on the API loss was also observed. The presence of a chemical
      molecule effect on the API loss was demonstrated through data mining using a set
      of assay results containing 17 different molecules and 1922 assay values. The 17
      median assay values were modeled in function of corresponding molecular
      descriptors, using stepwise multiple linear regression. The obtained MLR model,
      containing RDF060m, R6e(+) and R3m(+) variables, explained 92.5% of the observed
      variability between the 17 median assay values. 

PMID- 24727283
TI  - Two-dimensional correlation infrared spectroscopy applied to analyzing and
      identifying the extracts of Baeckea frutescens medicinal materials.
AB  - Baeckea frutescens or locally known as Cucur atap is used as antibacterial,
      antidysentery, antipyretic and diuretic agent. In Malaysia and Indonesia, they
      are used as an ingredient of the traditional medicine given to mothers during
      confinement. A three-steps infra-red (IR) macro-fingerprinting method combining
      conventional IR spectra, and the secondary derivative spectra with two
      dimensional infrared correlation spectroscopy (2D-IR) have been proved to be
      effective methods to examine a complicated mixture such as herbal medicines. This
      study investigated the feasibility of employing multi-steps IR spectroscopy in
      order to study the main constituents of B. frutescens and its different extracts
      (extracted by chloroform, ethyl acetate, methanol and aqueous in turn). The
      findings indicated that FT-IR and 2D-IR can provide many holistic variation rules
      of chemical constituents. The structural information of the samples indicated
      that B. frutescens and its extracts contain a large amount of flavonoids, since
      some characteristic absorption peaks of flavonoids, such as ~1600cm(-1), ~1500cm(
      1), ~1450cm(-1), and ~1270cm(-1) can be observed. The macroscopical fingerprint
      characters of FT-IR and 2D-IR spectra can not only provide the information of
      main chemical constituents in medicinal materials and their different extracts,
      but also compare the components differences among the similar samples. In
      conclusion, the multi-steps IR macro-fingerprint method is rapid, effective,
      visual and accurate for pharmaceutical research. 

PMID- 24727285
TI  - Tunnel diode oscillator measurements of the upper critical magnetic field of
      FeTe(0.5)Se(0.5).
AB  - Temperature dependence of the upper critical magnetic field (Hc2) of single
      crystalline FeTe0.5Se0.5(Tc = 14.5 K) have been determined by tunnel diode
      oscillator-based measurements in magnetic fields of up to 55 T and temperatures
      down to 1.6 K. The Werthamer-Helfand-Hohenberg model accounts for the data for
      magnetic field applied both parallel (H || ab) and perpendicular (H || c) to the
      iron conducting plane, in line with a single band superconductivity. Whereas
      Pauli pair breaking is negligible for H || c, Pauli contribution is evidenced for
      H || ab with Maki parameter alpha = 1.4, corresponding to Pauli field HP = 79 T.
      As a result, the Hc2 anisotropy [Formula: see text] which is already rather small
      at Tc (gamma = 1.6) further decreases as the temperature decreases and becomes
      smaller than 1 at liquid helium temperatures.

PMID- 24727284
TI  - Breast cancer stem cells: Multiple capacities in tumor metastasis.
AB  - Breast cancer is the leading cause of cancer death among women worldwide.
      Accumulating evidence indicates that the local recurrent and/or distant
      metastatic tumors, the major causes of lethality in the clinic, are related to
      the aggressive phenotype of a small fraction of cancer cells loosely termed as
      cancer stem cells (CSCs), tumor initiating cells (TICs), or cancer metastasis
      initiating cells (CMICs). Breast cancer stem cells (BCSCs) are shown to exhibit
      unique growth abilities including self-renewal, differentiation potential, and
      resistance to most anti-cancer agents including chemo- and/or radiotherapy, all
      of which are believed to contribute to the development and overall aggressiveness
      of the recurrent or metastatic lesions. It is in the urgent need not only to
      further define the nature of heterogeneity in each tumor but also to characterize
      the precise mechanisms governing tumor-host cross-talk which is assumed to be
      initiated by BCSCs. In this review, we will focus on recently identified key
      factors, including the BCSCs among circulating tumor cells, interaction of BCSCs
      with the host, epithelial mesenchymal transition (EMT), tumor microenvironment,
      the intrinsic resistance due to HER2 expression, potential biomarkers of BCSCs
      and cancer cell immune signaling. We believe that new evidence coming from both
      bench and clinical research will help to develop more effective approaches to
      control or significantly reduce the aggressiveness of metastatic tumors.

PMID- 24727286
TI  - Genetics and evolution: an iOS application to supplement introductory courses in
      transmission and evolutionary genetics.
AB  - Students in college courses struggle to understand many concepts fundamental to
      transmission and evolutionary genetics, including multilocus inheritance,
      recombination, Hardy-Weinberg, and genetic drift. These students consistently ask
      for more demonstrations and more practice problems. With this demand in mind, the
      "Genetics and Evolution" app was designed to help students (and their
      instructors) by providing a suite of tools granting them the ability to: (1)
      simulate genetic crosses with varying numbers of genes and patterns of
      inheritance, (2) simulate allele frequency changes under natural selection and/
      or genetic drift, (3) quiz themselves to reinforce terminology (customizable by
      any instructor for their whole classroom), *4) solve various problems
      (recombination fractions, Hardy-Weinberg, heritability, population growth), and
      (5) generate literally an infinite number of practice problems in all of these
      areas to try on their own. Although some of these functions are available
      elsewhere, the alternatives do not have the ability to instantly generate new
      practice problems or achieve these diverse functions in devices that students
      carry in their pockets every day. 

PMID- 24727288
TI  - Rapid evolution of phenotypic plasticity and shifting thresholds of genetic
      assimilation in the nematode Caenorhabditis remanei.
AB  - Many organisms can acclimate to new environments through phenotypic plasticity, a
      complex trait that can be heritable, subject to selection, and evolve. However,
      the rate and genetic basis of plasticity evolution remain largely unknown. We
      experimentally evolved outbred populations of the nematode Caenorhabditis remanei
      under an acute heat shock during early larval development. When raised in a
      nonstressful environment, ancestral populations were highly sensitive to a 36.8
      degrees  heat shock and exhibited high mortality. However, initial exposure to a
      nonlethal high temperature environment resulted in significantly reduced
      mortality during heat shock (hormesis). Lines selected for heat shock resistance
      rapidly evolved the capacity to withstand heat shock in the native environment
      without any initial exposure to high temperatures, and early exposure to high
      temperatures did not lead to further increases in heat resistance. This loss of
      plasticity would appear to have resulted from the genetic assimilation of the
      heat induction response in the noninducing environment. However, analyses of
      transcriptional variation via RNA-sequencing from the selected populations
      revealed no global changes in gene regulation correlated with the observed
      changes in heat stress resistance. Instead, assays of the phenotypic response
      across a broader range of temperatures revealed that the induced plasticity was
      not fixed across environments, but rather the threshold for the response was
      shifted to higher temperatures over evolutionary time. These results demonstrate
      that apparent genetic assimilation can result from shifting thresholds of
      induction across environments and that analysis of the broader environmental
      context is critically important for understanding the evolution of phenotypic
      plasticity. 

PMID- 24727287
TI  - A recent global selective sweep on the age-1 phosphatidylinositol 3-OH kinase
      regulator of the insulin-like signaling pathway within Caenorhabditis remanei.
AB  - The discovery that genetic pathways can be manipulated to extend lifespan has
      revolutionized our understanding of aging, yet their function within natural
      populations remains poorly characterized. In particular, evolutionary theories of
      aging predict tradeoffs in resource investment toward somatic maintenance vs.
      reproductive output that should impose strong natural selection on genetic
      components that influence this balance. To explore such selective pressure at the
      molecular level, we examine population genetic variation in the insulin-like
      signaling pathway of the nematode Caenorhabditis remanei. We document a recent
      global selective sweep on the phosphoinositide-3-kinase pathway regulator, age-1,
      the first life-extension gene to have been identified. In particular, we find
      that age-1 has 5-20 times less genetic variation than any other insulin-like
      signaling pathway components and that evolutionary signatures of selection center
      on the age-1 locus within its genomic environment. These results demonstrate that
      critical components of aging-related pathways can be subject to shifting patterns
      of strong selection, as predicted by theory. This highly polymorphic outcrossing
      species offers high-resolution, population-level analyses of molecular variation
      as a complement to functional genetic studies within the self-reproducing C.
      elegans model system. 

PMID- 24727289
TI  - Parametric and nonparametric statistical methods for genomic selection of traits
      with additive and epistatic genetic architectures.
AB  - Parametric and nonparametric methods have been developed for purposes of
      predicting phenotypes. These methods are based on retrospective analyses of
      empirical data consisting of genotypic and phenotypic scores. Recent reports have
      indicated that parametric methods are unable to predict phenotypes of traits with
      known epistatic genetic architectures. Herein, we review parametric methods
      including least squares regression, ridge regression, Bayesian ridge regression,
      least absolute shrinkage and selection operator (LASSO), Bayesian LASSO, best
      linear unbiased prediction (BLUP), Bayes A, Bayes B, Bayes C, and Bayes Cpi. We
      also review nonparametric methods including Nadaraya-Watson estimator,
      reproducing kernel Hilbert space, support vector machine regression, and neural
      networks. We assess the relative merits of these 14 methods in terms of accuracy
      and mean squared error (MSE) using simulated genetic architectures consisting of
      completely additive or two-way epistatic interactions in an F2 population derived
      from crosses of inbred lines. Each simulated genetic architecture explained
      either 30% or 70% of the phenotypic variability. The greatest impact on estimates
      of accuracy and MSE was due to genetic architecture. Parametric methods were
      unable to predict phenotypic values when the underlying genetic architecture was
      based entirely on epistasis. Parametric methods were slightly better than
      nonparametric methods for additive genetic architectures. Distinctions among
      parametric methods for additive genetic architectures were incremental.
      Heritability, i.e., proportion of phenotypic variability, had the second greatest
      impact on estimates of accuracy and MSE. 

PMID- 24727290
TI  - In Aspergillus nidulans the suppressors suaA and suaC code for release factors
      eRF1 and eRF3 and suaD codes for a glutamine tRNA.
AB  - In Aspergillus nidulans, after extensive mutagenesis, a collection of mutants was
      obtained and four suppressor loci were identified genetically that could suppress
      mutations in putative chain termination mutations in different genes. Suppressor
      mutations in suaB and suaD have a similar restricted spectrum of suppression and
      suaB111 was previously shown to be an alteration in the anticodon of a gln tRNA.
      We have shown that like suaB, a suaD suppressor has a mutation in the anticodon
      of another gln tRNA allowing suppression of UAG mutations. Mutations in suaA and
      suaC had a broad spectrum of suppression. Four suaA mutations result in
      alterations in the coding region of the eukaryotic release factor, eRF1, and
      another suaA mutation has a mutation in the upstream region of eRF1 that prevents
      splicing of the first intron within the 5'UTR. Epitope tagging of eRF1 in this
      mutant results in 20% of the level of eRF1 compared to the wild-type. Two
      mutations in suaC result in alterations in the eukaryotic release factor, eRF3.
      This is the first description in Aspergillus nidulans of an alteration in eRF3
      leading to suppression of chain termination mutations.

PMID- 24727291
TI  - A genome-wide screen for sporulation-defective mutants in Schizosaccharomyces
      pombe.
AB  - Yeast sporulation is a highly regulated developmental program by which diploid
      cells generate haploid gametes, termed spores. To better define the genetic
      pathways regulating sporulation, a systematic screen of the set of ~3300
      nonessential Schizosaccharomyces pombe gene deletion mutants was performed to
      identify genes required for spore formation. A high-throughput genetic method was
      used to introduce each mutant into an h(90) background, and iodine staining was
      used to identify sporulation-defective mutants. The screen identified 34 genes
      whose deletion reduces sporulation, including 15 that are defective in forespore
      membrane morphogenesis. In S. pombe, the total number of sporulation-defective
      mutants is a significantly smaller fraction of coding genes than in S.
      cerevisiae, which reflects the different evolutionary histories and biology of
      the two yeasts. 

PMID- 24727292
TI  - Modelling crash propensity of carshare members.
AB  - Carshare systems are considered a promising solution for sustainable development
      of cities. To promote carsharing it is imperative to make them cost effective,
      which includes reduction in costs associated to crashes and insurance. To achieve
      this goal, it is important to characterize carshare users involved in crashes and
      understand factors that can explain at-fault and not-at fault drivers. This study
      utilizes data from GoGet carshare users in Sydney, Australia. Based on this study
      it was found that carshare users who utilize cars less frequently, own one or
      more cars, have less number of accidents in the past ten years, have chosen a
      higher insurance excess and have had a license for a longer period of time are
      less likely to be involved in a crash. However, if a crash occurs, carshare users
      not needing a car on the weekend, driving less than 1000km in the last year,
      rarely using a car and having an Australian license increases the likelihood to
      be at-fault. Since the dataset contained information about all members as well as
      not-at-fault drivers, it provided a unique opportunity to explore some aspects of
      quasi-induced exposure. The results indicate systematic differences in the
      distribution between the not-at-fault drivers and the carshare members based on
      the kilometres driven last year, main mode of travel, car ownership status and
      how often the car is needed. Finally, based on this study it is recommended that
      creating an incentive structure based on training and experience (based on
      kilometres driven), possibly tagged to the insurance excess could improve safety,
      and reduce costs associated to crashes for carshare systems. 

PMID- 24727293
TI  - Mercury exposure in a large subantarctic avian community.
AB  - Mercury (Hg) contamination poses potential threats to ecosystems worldwide. In
      order to study Hg bioavailability in the poorly documented southern Indian Ocean,
      Hg exposure was investigated in the large avian community of Kerguelen Islands.
      Adults of 27 species (480 individuals) showed a wide range of feather Hg
      concentrations, from 0.4 +/- 0.1 to 16.6 +/- 3.8 MUg g(-1) dry weight in Wilson's
      storm petrels and wandering albatrosses, respectively. Hg concentrations
      increased roughly in the order crustacean- < fish- <= squid- <= carrion
      consumers, confirming that diet, rather than taxonomy, is an important driver of
      avian Hg exposure. Adults presented higher Hg concentrations than chicks, due to
      a longer duration of exposure, with the only exception being the subantarctic
      skua, likely because of feeding habits' differences of the two age-classes in
      this species. High Hg concentrations were reported for three species of the
      poorly known gadfly petrels, which merit further investigation. 

PMID- 24727294
TI  - Astrocytic plasticity as a possible mediator of the cognitive improvements after
      environmental enrichment in aged rats.
AB  - Currently, little is known about the effect of environmental enrichment (EE) on
      astrocytic plasticity, especially during aging. Given the newly discovered role
      of the astrocytes in regulating the synaptic transmission and thereby, the
      cognitive functions, we aimed to study the impact of EE on the performance in a
      spatial memory task and on the number and morphology of GFAP immunopositive cells
      in the dorsal hippocampus. After two months of EE (3 h/per day), the animals were
      tested in the Radial-Arm Water Maze (RAWM) for four days, with six daily trials.
      Next, we analyzed the changes in the GFAP immunopositive cells in CA1, CA3 and
      Dentate Gyrus (DG). Behavioral results showed that, even in advanced ages, EE
      improved the performance in a spatial memory task. Also, we found that aged rats
      submitted to EE had more GFAP immunopositive cells in the DG and more complex
      astrocytes, revealed by Sholl analysis, in all hippocampal subfields with respect
      to the other experimental conditions. Interestingly, the learning of a spatial
      memory task produced more morphological complexity and higher levels of GFAP
      immunopositive cells with regard to a standard control group, but not at the same
      level of the enriched groups. Thus, it is possible that the plastic changes found
      in the hippocampal astrocytes after EE are involved in a brain reserve to cope
      with age-related cognitive impairments.

PMID- 24727295
TI  - Children's skepticism: developmental and individual differences in children's
      ability to detect and explain distorted claims.
AB  - The current study examined some key developmental and individual differences in
      how elementary school-aged children evaluate sources of information. A sample of
      130 children ages 6 to 9 years participated in a task designed to measure
      children's understanding of ways that claims can be distorted (i.e., biased
      decisions, skewed self-reports, and misleading persuasive claims). Children also
      completed several individual difference measures, including a brief intelligence
      task and an advanced social cognition measure (interpretive theory of mind).
      Overall, older children were less trusting and better than younger children at
      explaining the reasons to doubt sources that might provide distorted claims.
      Crucially, the results also suggest that beyond age, both general intelligence
      and advanced social cognitive skills play roles in children's ability to
      understand when and why they must doubt sources of distortion.

PMID- 24727296
TI  - Is selective attention the basis for selective imitation in infants? An eye
      tracking study of deferred imitation with 12-month-olds.
AB  - Infants and children do not blindly copy every action they observe during
      imitation tasks. Research demonstrated that infants are efficient selective
      imitators. The impact of selective perceptual processes (selective attention) for
      selective deferred imitation, however, is still poorly described. The current
      study, therefore, analyzed 12-month-old infants' looking behavior during
      demonstration of two types of target actions: arbitrary versus functional
      actions. A fully automated remote eye tracker was used to assess infants' looking
      behavior during action demonstration. After a 30-min delay, infants' deferred
      imitation performance was assessed. Next to replicating a memory effect, results
      demonstrate that infants do imitate significantly more functional actions than
      arbitrary actions (functionality effect). Eye-tracking data show that whereas
      infants do not fixate significantly longer on functional actions than on
      arbitrary actions, amount of fixations and amount of saccades differ between
      functional and arbitrary actions, indicating different encoding mechanisms. In
      addition, item-level findings differ from overall findings, indicating that
      perceptual and conceptual item features influence looking behavior. Looking
      behavior on both the overall and item levels, however, does not relate to
      deferred imitation performance. Taken together, the findings demonstrate that, on
      the one hand, selective imitation is not explainable merely by selective
      attention processes. On the other hand, notwithstanding this reasoning, attention
      processes on the item level are important for encoding processes during target
      action demonstration. Limitations and future studies are discussed.

PMID- 24727298
TI  - Ireland considers compulsory health insurance for all and subsidised premiums for
      least well off.

PMID- 24727299
TI  - Italy drops ban on infertile couples using donated eggs or sperm.

PMID- 24727297
TI  - Psychostimulant addiction treatment.
AB  - Treatment of psychostimulant addiction has been a major, and not fully met,
      challenge. For opioid addiction, there is strong evidence for the effectiveness
      of several medications. For psychostimulants, there is no corresponding form of
      agonist maintenance that has met criteria for regulatory approval or generally
      accepted use. Stimulant-use disorders remain prevalent and can result in both
      short-term and long-term adverse consequences. The mainstay of treatment remains
      behavioral interventions. In this paper, we discuss those interventions and some
      promising candidates in the search for pharmacological interventions. This
      article is part of the Special Issue entitled 'CNS Stimulants'. 

PMID- 24727300
TI  - Law to broaden access to contraception gets green light in Philippines.

PMID- 24727301
TI  - Florida ophthalmologist received almost $21m from Medicare in one year.

PMID- 24727302
TI  - US website is launched to share cancer trial data.

PMID- 24727303
TI  - RCGP is cleared of ethnic discrimination in clinical skills assessment.

PMID- 24727305
TI  - Improving the evidence base in palliative care to inform practice and policy:
      thinking outside the box.
AB  - The adoption of evidence-based hierarchies and research methods from other
      disciplines may not completely translate to complex palliative care settings. The
      heterogeneity of the palliative care population, complexity of clinical
      presentations, and fluctuating health states present significant research
      challenges. The aim of this narrative review was to explore the debate about the
      use of current evidence-based approaches for conducting research, such as
      randomized controlled trials and other study designs, in palliative care, and
      more specifically to (1) describe key myths about palliative care research; (2)
      highlight substantive challenges of conducting palliative care research, using
      case illustrations; and (3) propose specific strategies to address some of these
      challenges. Myths about research in palliative care revolve around evidence
      hierarchies, sample heterogeneity, random assignment, participant burden, and
      measurement issues. Challenges arise because of the complex physical,
      psychological, existential, and spiritual problems faced by patients, families,
      and service providers. These challenges can be organized according to six general
      domains: patient, system/organization, context/setting, study design, research
      team, and ethics. A number of approaches for dealing with challenges in
      conducting research fall into five separate domains: study design, sampling,
      conceptual, statistical, and measures and outcomes. Although randomized
      controlled trials have their place whenever possible, alternative designs may
      offer more feasible research protocols that can be successfully implemented in
      palliative care. Therefore, this article highlights "outside the box" approaches
      that would benefit both clinicians and researchers in the palliative care field.
      Ultimately, the selection of research designs is dependent on a clearly
      articulated research question, which drives the research process.

PMID- 24727304
TI  - Assembly, heterogeneity, and breaching of the basement membranes.
AB  - Basement membranes are thin sheets of self-assembled extracellular matrices that
      are essential for embryonic development and for the homeostasis of adult tissues.
      They play a role in structuring, protecting, polarizing, and compartmentalizing
      cells, as well as in supplying them with growth factors. All basement membranes
      are built from laminin and collagen IV networks stabilized by nidogen/perlecan
      bridges. The precise composition of basement membranes, however, varies between
      different tissues. Even though basement membranes represent physical barriers
      that delimit different tissues, they are breached in many physiological or
      pathological processes, including development, the immune response, and tumor
      invasion. Here, we provide a brief overview of the molecular composition of
      basement membranes and the process of their assembly. We will then illustrate the
      heterogeneity of basement membranes using two examples, the epithelial basement
      membrane in the gut and the vascular basement membrane. Finally, we examine the
      different strategies cells use to breach the basement membrane. 

PMID- 24727306
TI  - Does the working environment influence health care professionals' values, meaning
      in life and religiousness? Palliative care units compared with maternity wards.
AB  - CONTEXT: Increased altruism, self-transcendence, and quests for meaning in life
      (MiL) have been found in palliative care (PC) patients and their families who
      experience the finiteness of life. Similar changes were observed in healthy
      subjects who were experimentally confronted with their mortality. OBJECTIVES: The
      study investigated how daily experiences of the transitoriness of life influence
      PC health care professionals' (HCPs) values, MiL, and religiousness. METHODS: In
      a cross-sectional study, the Schwartz Value Survey, the Schedule for Meaning in
      Life Evaluation, and the Idler Index of Religiosity were used to investigate
      personal values, MiL, and private religiousness. HCPs working in PC (confronted
      with death) were compared with a control group of HCPs working at maternity wards
      (MWs) using multivariate models. Differences were considered to be statistically
      significant at P < 0.05. RESULTS: Seventy PC- and 70 MW-HCPs took part in the
      study (response rate 74.0%). No differences between the groups were found in
      overall MiL satisfaction scores. PC-HCPs were significantly more religious than
      MW-HCPs; they listed spirituality and nature experience more often as areas in
      which they experience MiL. Furthermore, hedonism was more important for PC-HCPs,
      and they had higher scores in openness-to-change values (stimulation and self
      direction). MW-HCPs were more likely to list family as a MiL area. They assigned
      more importance to health and scored higher in conservation values (conformity
      and security). Duration of professional experience did not influence these
      results. CONCLUSION: Basic differences in values, MiL, and religiousness between
      PC-HCPs and MW-HCPs might have influenced the choice of working environment
      because no effect of job duration was observed. Longitudinal research is needed
      to confirm this hypothesis.

PMID- 24727308
TI  - Comment: Awareness in partial seizures--implications for patients and therapies.

PMID- 24727307
TI  - Polygenic scores predict alcohol problems in an independent sample and show
      moderation by the environment.
AB  - Alcohol problems represent a classic example of a complex behavioral outcome that
      is likely influenced by many genes of small effect. A polygenic approach, which
      examines aggregate measured genetic effects, can have predictive power in cases
      where individual genes or genetic variants do not. In the current study, we first
      tested whether polygenic risk for alcohol problems-derived from genome-wide
      association estimates of an alcohol problems factor score from the age 18
      assessment of the Avon Longitudinal Study of Parents and Children (ALSPAC; n =
      4304 individuals of European descent; 57% female)-predicted alcohol problems
      earlier in development (age 14) in an independent sample (FinnTwin12; n = 1162;
      53% female). We then tested whether environmental factors (parental knowledge and
      peer deviance) moderated polygenic risk to predict alcohol problems in the
      FinnTwin12 sample. We found evidence for both polygenic association and for
      additive polygene-environment interaction. Higher polygenic scores predicted a
      greater number of alcohol problems (range of Pearson partial correlations 0.07
      0.08, all p-values <= 0.01). Moreover, genetic influences were significantly more
      pronounced under conditions of low parental knowledge or high peer deviance
      (unstandardized regression coefficients (b), p-values (p), and percent of
      variance (R2) accounted for by interaction terms: b = 1.54, p = 0.02, R2 = 0.33%;
      b = 0.94, p = 0.04, R2 = 0.30%, respectively). Supplementary set-based analyses
      indicated that the individual top single nucleotide polymorphisms (SNPs)
      contributing to the polygenic scores were not individually enriched for gene
      environment interaction. Although the magnitude of the observed effects are
      small, this study illustrates the usefulness of polygenic approaches for
      understanding the pathways by which measured genetic predispositions come
      together with environmental factors to predict complex behavioral outcomes. 

PMID- 24727309
TI  - Venous thromboembolism in amyotrophic lateral sclerosis: a prospective study.
AB  - OBJECTIVE: To prospectively assess the incidence of both symptomatic and
      asymptomatic venous thromboembolism (VTE) in patients with amyotrophic lateral
      sclerosis (ALS) and to identify risk factors. METHODS: Fifty outpatients with ALS
      were recruited consecutively and prospectively evaluated with bilateral venous
      duplex ultrasonography (VDU) of the proximal leg veins at enrollment and 6 and 12
      months. The primary outcome measure was clinically important VTE, defined as
      asymptomatic proximal deep vein thrombosis (DVT) by screening VDU,
      symptomatically proven DVT or pulmonary embolism (PE), or fatal PE. For each
      patient, person-days of follow-up were recorded from enrollment until the date of
      VTE, death, loss to follow-up, or final 12-month visit. RESULTS: During the 1
      year follow-up period, VTE was detected in 4 patients (1 symptomatic DVT, 1
      symptomatic PE, and 2 asymptomatic DVTs) over 13,011 person-days of follow-up,
      representing an 11.2% 1-year incidence. Subjects with leg-onset ALS or
      significant leg weakness had a 1-year VTE incidence rate of 35.8% and 35.5%,
      respectively. VTE risk was significantly increased for those patients with
      decreased lower extremity Revised ALS Functional Rating Scale subscore (p =
      0.03), decreased Lower Extremity Activity Scale score (p = 0.02), and decreased
      average lower limb Medical Research Council scale strength score (p = 0.03).
      CONCLUSIONS: Our data suggest that clinically important VTE is common in patients
      with ALS, particularly those with leg weakness and reduced mobility. Given these
      results, the potential benefits of routine VTE screening and primary prophylaxis
      in high-risk patients with ALS with leg weakness should be explored in future
      studies. In the meantime, physicians should have a low threshold for considering
      VTE in patients with ALS with leg weakness.

PMID- 24727310
TI  - Reevaluating the risk of DVT in people with ALS: weak in the knees and DVTs.

PMID- 24727311
TI  - Impaired consciousness in partial seizures is bimodally distributed.
AB  - OBJECTIVE: To investigate whether impaired consciousness in partial seizures can
      usually be attributed to specific deficits in the content of consciousness or to
      a more general decrease in the overall level of consciousness. METHODS:
      Prospective testing during partial seizures was performed in patients with
      epilepsy using the Responsiveness in Epilepsy Scale (n = 83 partial seizures, 30
      patients). Results were compared with responsiveness scores in a cohort of
      patients with severe traumatic brain injury evaluated with the JFK Coma Recovery
      Scale-Revised (n = 552 test administrations, 184 patients). RESULTS: Standardized
      testing during partial seizures reveals a bimodal scoring distribution, such that
      most patients were either fully impaired or relatively spared in their ability to
      respond on multiple cognitive tests. Seizures with impaired performance on
      initial test items remained consistently impaired on subsequent items, while
      other seizures showed spared performance throughout. In the comparison group, we
      found that scores of patients with brain injury were more evenly distributed
      across the full range in severity of impairment. CONCLUSIONS: Partial seizures
      can often be cleanly separated into those with vs without overall impaired
      responsiveness. Results from similar testing in a comparison group of patients
      with brain injury suggest that the bimodal nature of Responsiveness in Epilepsy
      Scale scores is not a result of scale bias but may be a finding unique to partial
      seizures. These findings support a model in which seizures either propagate or do
      not propagate to key structures that regulate overall arousal and thalamocortical
      function. Future investigations are needed to relate these behavioral findings to
      the physiology underlying impaired consciousness in partial seizures.

PMID- 24727312
TI  - Carotid plaque inflammation in stroke assessed by PET: a burning issue?

PMID- 24727313
TI  - Serum lipids associated with inflammation-related PET-FDG uptake in symptomatic
      carotid plaque.
AB  - OBJECTIVE: We hypothesized that serum lipids, which experimental data suggest may
      be key initiators of carotid plaque inflammation, would be associated with plaque
      inflammation on (18)fluorodeoxyglucose (FDG)-PET in patients with acutely
      symptomatic carotid stenosis. METHODS: In this cohort study, consecutive patients
      with acute symptomatic internal carotid artery (ICA) stenosis (>=50%) underwent
      carotid PET-CT. We quantified plaque FDG uptake as follows: (1) average maximum
      standardized uptake values (SUVmax) across 10 regions of interest (ROI); (2)
      highest single ROI SUV measure (SUVROImax); (3) averaged mean SUV across 10 ROIs
      (SUVmean). RESULTS: Sixty-one patients were included. Plaque inflammatory FDG
      SUVmax was associated with increasing tertiles of low-density lipoprotein (LDL)
      (trend p = 0.004), total cholesterol (p = 0.009), and triglycerides (p = 0.01),
      and with lower high-density lipoprotein (HDL) (p = 0.005). When analyzed as a
      continuous variable, LDL was associated with symptomatic ICA SUVmean (Spearman
      rho 0.44, p = 0.009), SUVROImax (rho 0.33, p = 0.01), and SUVmax (rho 0.35, p =
      0.06). Total cholesterol was associated with SUVmean (rho 0.33, p = 0.009), with
      trends for SUVmax (rho 0.24, p = 0.059) and SUVROImax (rho 0.23, p = 0.08).
      Triglycerides were associated with SUVmax (rho 0.32, p = 0.01) and SUVROImax (rho
      0.35, p = 0.005). HDL was associated with lower SUVmax (rho -0.37, p = 0.004) and
      SUVROImax (rho -0.44, p = 0.0004). On multivariable linear regression analysis
      adjusting for age, sex, degree of carotid stenosis, statins, and smoking, LDL (p
      = 0.008) and total cholesterol (p = 0.04) were independently associated with
      SUVmax. CONCLUSION: Serum LDL and total cholesterol were associated with acutely
      symptomatic carotid plaque FDG uptake, supporting experimental data suggesting
      lipids may promote plaque inflammation, mediating rupture and clinical events.

PMID- 24727314
TI  - Progression types after antiangiogenic therapy are related to outcome in
      recurrent glioblastoma.
AB  - OBJECTIVE: This retrospective study analyzed whether the type of radiologic
      progression, classified according to contrast enhancement on MRI T1-weighted
      sequences and changes in T2-hyperintense signal, is relevant for outcome in
      patients with progressive glioblastoma (pGB) treated with bevacizumab. METHODS:
      MRI scans of 83 patients with pGB treated with bevacizumab were evaluated prior
      to and at disease progression. Based on initial decrease in and subsequent flare
      up of contrast enhancement in T1 and 2 patterns of T2-hyperintense tumor
      progression, progression types (PTs) were categorized as cT1 flare-up, T2
      diffuse, T2-circumscribed, or primary nonresponder. Overall survival (OS),
      survival from start of bevacizumab therapy (OS_Bev), survival after bevacizumab
      failure (OS_PostBev), time from initial diagnosis until initiation of bevacizumab
      therapy (StartBevT), and time to bevacizumab progression were evaluated using
      Kaplan-Meier curves, log-rank test, and Cox regression analyses. RESULTS: The
      time observed for development of a T2-diffuse (n = 15) or a cT1 flare-up (n = 35)
      progression was longer than for progression in primary nonresponders (n = 16) or
      T2-circumscribed progression (n = 17). The T2-diffuse PT showed longer OS,
      OS_Bev, OS_PostBev, and StartBevT compared to the other PTs. Postprogression
      therapy tended to be relevant only for patients with a T2-circumscribed PT.
      CONCLUSIONS: Radiologic PTs following bevacizumab treatment failure show
      differences in time to development and are related to outcome. We therefore
      hypothesize that these PTs reflect a different glioma biology, including
      differential resistance mechanisms to bevacizumab, and may be associated with
      different responses to postprogression therapy.

PMID- 24727315
TI  - Nonverbal oral apraxia in primary progressive aphasia and apraxia of speech.
AB  - OBJECTIVE: The goal of this study was to explore the prevalence of nonverbal oral
      apraxia (NVOA), its association with other forms of apraxia, and associated
      imaging findings in patients with primary progressive aphasia (PPA) and
      progressive apraxia of speech (PAOS). METHODS: Patients with a degenerative
      speech or language disorder were prospectively recruited and diagnosed with a
      subtype of PPA or with PAOS. All patients had comprehensive speech and language
      examinations. Voxel-based morphometry was performed to determine whether atrophy
      of a specific region correlated with the presence of NVOA. RESULTS: Eighty-nine
      patients were identified, of which 34 had PAOS, 9 had agrammatic PPA, 41 had
      logopenic aphasia, and 5 had semantic dementia. NVOA was very common among
      patients with PAOS but was found in patients with PPA as well. Several patients
      exhibited only one of NVOA or apraxia of speech. Among patients with apraxia of
      speech, the severity of the apraxia of speech was predictive of NVOA, whereas
      ideomotor apraxia severity was predictive of the presence of NVOA in those
      without apraxia of speech. Bilateral atrophy of the prefrontal cortex anterior to
      the premotor area and supplementary motor area was associated with NVOA.
      CONCLUSIONS: Apraxia of speech, NVOA, and ideomotor apraxia are at least
      partially separable disorders. The association of NVOA and apraxia of speech
      likely results from the proximity of the area reported here and the premotor
      area, which has been implicated in apraxia of speech. The association of
      ideomotor apraxia and NVOA among patients without apraxia of speech could
      represent disruption of modules shared by nonverbal oral movements and limb
      movements.

PMID- 24727316
TI  - Bevacizumab for glioblastoma: what can we learn from patterns of progression?

PMID- 24727317
TI  - Clinical import of Horner syndrome in internal carotid and vertebral artery
      dissection.
AB  - OBJECTIVE: To study the prognostic importance of Horner syndrome (HS) in patients
      with internal carotid artery dissection (ICAD) or vertebral artery dissection
      (VAD). METHODS: In this observational study, characteristics and outcome of
      patients with ICAD or VAD from the CADISP (Cervical Artery Dissection and
      Ischemic Stroke Patients) database were analyzed. The presence of HS was
      systematically assessed using a standardized questionnaire. Patients with HS
      (HS+) were compared with HS- patients. Crude odds ratios (ORs) with 95%
      confidence intervals and ORs adjusted for age, sex, center, arterial occlusion,
      bilateral dissection, stroke severity, and type of antithrombotic treatment were
      calculated. RESULTS: We analyzed 765 patients (n = 496 with ICAD, n = 269 with
      VAD, n = 303 prospective, n = 462 retrospective). HS was present in 191 (38.5%)
      of the patients with ICAD and 36 (13.4%) of the patients with VAD (p < 0.001).
      HS+ ICAD patients presented less often with stroke or TIA (p < 0.001), less often
      had bilateral (p = 0.019) or occlusive (p = 0.001) dissections, and had fewer
      severe strokes (p = 0.041) than HS- ICAD patients. HS+ ICAD patients had a better
      functional 3-month outcome than those without HS (ORcrude = 4.0 [2.4-6.7]), and
      also after adjustment for outcome-relevant covariates (ORadjusted = 2.0 [1.1
      4.0]). HS+ ICAD patients were less likely to have new strokes than HS- ICAD
      patients (p = 0.039). HS+ VAD patients more often had vessel occlusion (p =
      0.014) than HS- patients but did not differ in any of the other aforementioned
      variables. CONCLUSION: In patients with ICAD, HS is an easily assessable marker
      that might indicate a more benign clinical course. HS had no prognostic meaning
      in patients with VAD.

PMID- 24727318
TI  - Second-eye cataract surgery: valuable investment or unaffordable luxury?

PMID- 24727319
TI  - Phase transition of the uniaxial disordered ferroelectric
      Sr(0.61)Ba(0.39)Nb(2)O(6).
AB  - We report a neutron scattering study of a ferroelectric phase transition in
      Sr0.61Ba0.39Nb2O6 (SBN-61). The ferroelectric polarization is along the
      crystallographic c-axis but the transverse acoustic branch propagating along the
      <1, 1, 0> direction does not show any anomaly associated with this transition. We
      find no evidence for a soft transverse optic phonon. We do, however, observe
      elastic diffuse scattering. The intensity of this scattering increases as the
      sample is cooled from a temperature well above the phase transition. The
      susceptibility associated with this diffuse scattering follows the anomaly of the
      dielectric permittivity of SBN-61 well. Below Tc the shape of this scattering is
      consistent with the scattering expected from ferroelectric domain walls. Our
      results suggest that despite apparent chemical disorder SBN-61 behaves as a
      classic order-disorder uniaxial ferroelectric with critical fluctuations in the
      range <10(-11) s. 

PMID- 24727320
TI  - Druggable oncogene fusions in invasive mucinous lung adenocarcinoma.
AB  - PURPOSE: To identify druggable oncogenic fusions in invasive mucinous
      adenocarcinoma (IMA) of the lung, a malignant type of lung adenocarcinoma in
      which KRAS mutations frequently occur. EXPERIMENTAL DESIGN: From an IMA cohort of
      90 cases, consisting of 56 cases (62%) with KRAS mutations and 34 cases without
      (38%), we conducted whole-transcriptome sequencing of 32 IMAs, including 27 cases
      without KRAS mutations. We used the sequencing data to identify gene fusions, and
      then performed functional analyses of the fusion gene products. RESULTS: We
      identified oncogenic fusions that occurred mutually exclusively with KRAS
      mutations: CD74-NRG1, SLC3A2-NRG1, EZR-ERBB4, TRIM24-BRAF, and KIAA1468-RET. NRG1
      fusions were present in 17.6% (6/34) of KRAS-negative IMAs. The CD74-NRG1 fusion
      activated HER2:HER3 signaling, whereas the EZR-ERBB4 and TRIM24-BRAF fusions
      constitutively activated the ERBB4 and BRAF kinases, respectively. Signaling
      pathway activation and fusion-induced anchorage-independent growth/tumorigenicity
      of NIH3T3 cells expressing these fusions were suppressed by tyrosine kinase
      inhibitors approved for clinical use. CONCLUSIONS: Oncogenic fusions act as
      driver mutations in IMAs without KRAS mutations, and thus represent promising
      therapeutic targets for the treatment of such IMAs.

PMID- 24727321
TI  - Aggressive variants of castration-resistant prostate cancer.
AB  - A subset of patients with advanced castration-resistant prostate cancer may
      eventually evolve into an androgen receptor (AR)-independent phenotype, with a
      clinical picture associated with the development of rapidly progressive disease
      involving visceral sites and hormone refractoriness, often in the setting of a
      low or modestly rising serum prostate-specific antigen level. Biopsies performed
      in such patients may vary, ranging from poorly differentiated carcinomas to mixed
      adenocarcinoma-small cell carcinomas to pure small cell carcinomas. These
      aggressive tumors often demonstrate low or absent AR protein expression and, in
      some cases, express markers of neuroendocrine differentiation. Because tumor
      morphology is not always predicted by clinical behavior, the terms "anaplastic
      prostate cancer" or "neuroendocrine prostate cancer" have been used descriptively
      to describe these rapidly growing clinical features. Patients meeting clinical
      criteria of anaplastic prostate cancer have been shown to predict for poor
      prognosis, and these patients may be considered for platinum-based chemotherapy
      treatment regimens. Therefore, understanding variants within the spectrum of
      advanced prostate cancer has important diagnostic and treatment implications.

PMID- 24727323
TI  - CADM1 expression and stepwise downregulation of CD7 are closely associated with
      clonal expansion of HTLV-I-infected cells in adult T-cell leukemia/lymphoma.
AB  - PURPOSE: Cell adhesion molecule 1 (CADM1), initially identified as a tumor
      suppressor gene, has recently been reported to be ectopically expressed in
      primary adult T-cell leukemia-lymphoma (ATL) cells. We incorporated CADM1 into
      flow-cytometric analysis to reveal oncogenic mechanisms in human T-cell
      lymphotrophic virus type I (HTLV-I) infection by purifying cells from the
      intermediate stages of ATL development. EXPERIMENTAL DESIGN: We isolated CADM1-
      and CD7-expressing peripheral blood mononuclear cells of asymptomatic carriers
      and ATLs using multicolor flow cytometry. Fluorescence-activated cell sorted
      (FACS) subpopulations were subjected to clonal expansion and gene expression
      analysis. RESULTS: HTLV-I-infected cells were efficiently enriched in CADM1(+)
      subpopulations (D, CADM1(pos)CD7(dim) and N, CADM1(pos)CD7(neg)). Clonally
      expanding cells were detected exclusively in these subpopulations in asymptomatic
      carriers with high proviral load, suggesting that the appearance of D and N could
      be a surrogate marker of progression from asymptomatic carrier to early ATL.
      Further disease progression was accompanied by an increase in N with a reciprocal
      decrease in D, indicating clonal evolution from D to N. The gene expression
      profiles of D and N in asymptomatic carriers showed similarities to those of
      indolent ATLs, suggesting that these subpopulations represent premalignant cells.
      This is further supported by the molecular hallmarks of ATL, that is, drastic
      downregulation of miR-31 and upregulation of abnormal Helios transcripts.
      CONCLUSION: The CADM1 versus CD7 plot accurately reflects disease progression in
      HTLV-I infection, and CADM1(+) cells with downregulated CD7 in asymptomatic
      carriers have common properties with those in indolent ATLs.

PMID- 24727322
TI  - P-glycoprotein, CYP3A, and plasma carboxylesterase determine brain and blood
      disposition of the mTOR Inhibitor everolimus (Afinitor) in mice.
AB  - PURPOSE: To clarify the role of ABCB1, ABCG2, and CYP3A in blood and brain
      exposure of everolimus using knockout mouse models. EXPERIMENTAL DESIGN: We used
      wild-type, Abcb1a/1b(-/-), Abcg2(-/-), Abcb1a/1b;Abcg2(-/-), and Cyp3a(-/-) mice
      to study everolimus oral bioavailability and brain accumulation. RESULTS:
      Following everolimus administration, brain concentrations and brain-to-liver
      ratios were substantially increased in Abcb1a/1b(-/-)and Abcb1a/1b;Abcg2(-/-),
      but not Abcg2(-/-)mice. The fraction of everolimus located in the plasma
      compartment was highly increased in all knockout strains. In vitro, everolimus
      was rapidly degraded in wild-type but not knockout plasma. Carboxylesterase 1c
      (Ces1c), a plasma carboxylesterase gene, was highly upregulated (~80-fold) in the
      liver of knockout mice relative to wild-type mice, and plasma Ces1c likely
      protected everolimus from degradation by binding and stabilizing it. This binding
      was prevented by preincubation with the carboxylesterase inhibitor BNPP. In vivo
      knockdown experiments confirmed the involvement of Ces1c in everolimus
      stabilization. Everolimus also markedly inhibited the hydrolysis of irinotecan
      and p-nitrophenyl acetate by mouse plasma carboxylesterase and recombinant human
      CES2, respectively. After correcting for carboxylesterase binding, Cyp3a(-/-),
      but not Abcb1a/1b(-/-), Abcg2(-/-), or Abcb1a/1b;Abcg2(-/-)mice, displayed highly
      (>5-fold) increased oral availability of everolimus. CONCLUSIONS: Brain
      accumulation of everolimus was restricted by Abcb1, but not Abcg2, suggesting the
      use of coadministered ABCB1 inhibitors to improve brain tumor treatment. Cyp3a,
      but not Abcb1a/1b, restricted everolimus oral availability, underscoring drug
      drug interaction risks via CYP3A. Upregulated Ces1c likely mediated the tight
      binding and stabilization of everolimus, causing higher plasma retention in
      knockout strains. This Ces upregulation might confound other pharmacologic
      studies.

PMID- 24727324
TI  - A phase I trial of LY2510924, a CXCR4 peptide antagonist, in patients with
      advanced cancer.
AB  - PURPOSE: Overexpression of C-X-C motif receptor 4 (CXCR4) is implicated in tumor
      progression. LY2510924 is a peptide antagonist, which blocks stromal cell-derived
      factor-1 (SDF1) from CXCR4 binding. EXPERIMENTAL DESIGN: This phase I study
      included two parts: a 3+3 dose escalation (part A) and dose confirmation (part
      B). LY2510924 was administered as a daily subcutaneous injection on a 28-day
      cycle. The primary objective was to determine the recommended phase II dose.
      Secondary objectives included safety, pharmacokinetics, efficacy, and
      pharmacodynamic response, including mobilization of CD34(+) hematopoietic stem
      cells into the peripheral blood. RESULTS: Forty-five patients were enrolled, 25
      in part A and 20 in part B. Patients were administered increasing doses of
      LY2510924: 1.0, 2.5, 5.0, 10, 20, and 30 mg/day for part A and 2.5 or 20 mg/day
      for part B. Two patients (30-mg/day cohort) experienced dose-limiting toxicities
      of grade 3 increased neutrophil count. The maximum tolerated dose (MTD) was 20
      mg/day. The most common drug-related treatment-emergent adverse events were
      fatigue (9%), injection-site reaction (9%), injection site pruritus (7%), and
      nausea (7%). The best response was stable disease for nine patients (20%). At the
      end of cycle 1, mean peak LY2510924 plasma concentration and the 24-hour area
      under the plasma concentration versus time curve increased slightly more than
      dose proportionally. LY2510924 dose dependently increased CD34(+) cell counts in
      peripheral blood up to 18-fold. CONCLUSIONS: LY2510924 demonstrated CD34(+) cell
      mobilization at doses >=2.5 mg/day with a tolerable safety profile up to an MTD
      of 20 mg/day.

PMID- 24727325
TI  - Association study of the let-7 miRNA-complementary site variant in the 3'
      untranslated region of the KRAS gene in stage III colon cancer (NCCTG N0147
      Clinical Trial).
AB  - PURPOSE: A let-7 microRNA-complementary site (LCS6) polymorphism in the 3'
      untranslated region of the KRAS gene has been shown to disrupt let-7 binding and
      upregulate KRAS expression. We evaluated the LCS6 genotype and its association
      with KRAS mutation status, clinicopathologic features, and disease-free survival
      (DFS) in patients with stage III colon cancer who enrolled in a phase III
      clinical trial (NCCTG N0147). EXPERIMENTAL DESIGN: The LCS6 genotype was assayed
      by real-time PCR in DNA extracted from whole blood (n = 2,834) and compared with
      paired tumor tissue (n = 977). chi(2) and two-sample t tests were used to compare
      baseline factors and KRAS mutation status between patients defined by LCS6
      variant status. Log-rank tests and multivariate Cox models assessed associations
      between LCS6 status and DFS, respectively. RESULTS: We identified 432 (15.2%)
      blood samples and 143 (14.6%) tumor samples heterozygous or homozygous for the
      LCS6 G-allele, and 2,402 of 2,834 (84.8%) blood samples and 834 of 977 (85.4%)
      tumor samples homozygous for the LCS6 T-allele. Genotype results were highly
      concordant (99.8%) in cases with paired blood and tumor tissue (n = 977). G
      allele carriers were significantly more frequent in Caucasians versus other races
      (chi(2) test, P < 0.0001). The LCS6 genotype was not associated with KRAS
      mutation status, clinicopathologic features (all P > 0.2), or DFS (log-rank P =
      0.49; HR, 0.929; 95% confidence interval, 0.76-1.14), even after combining LCS6
      genotype with KRAS mutation status. CONCLUSIONS: In the largest association study
      investigating the LCS6 polymorphism in colon cancers, the germline LCS6 genotype
      was not associated with KRAS mutation status or with clinical outcome in patients
      with stage III tumors.

PMID- 24727326
TI  - Ganitumab (AMG 479) inhibits IGF-II-dependent ovarian cancer growth and
      potentiates platinum-based chemotherapy.
AB  - PURPOSE: Insulin-like growth factor 1 receptor (IGF-IR) has been implicated in
      the pathogenesis of ovarian cancer. Ganitumab is an investigational, fully human
      monoclonal antibody against IGF-IR. Here, we explore the therapeutic potential of
      ganitumab for the treatment of ovarian cancer. EXPERIMENTAL DESIGN: The effects
      of ganitumab were tested in vitro against a panel of 23 established ovarian
      cancer cell lines. The ability of ganitumab to inhibit IGF-I-, IGF-II-, and
      insulin-mediated signaling was examined in vitro and in tumor xenografts using
      ovarian cancer models displaying IGF-IR/PI3K/AKT pathway activation by two
      distinct mechanisms, PTEN loss and IGF-II overexpression. Drug interactions
      between ganitumab and cisplatin, carboplatin, or paclitaxel were studied in vitro
      and in vivo. RESULTS: In vitro, growth inhibition varied significantly among
      individual ovarian cancer cell lines. IGF-II mRNA and phospho-IGF-IR protein
      expression were quantitatively correlated with response to ganitumab, and PTEN
      mutations conferred resistance to ganitumab. Ganitumab potently inhibited
      baseline and IGF-I-, IGF-II-, and insulin-induced IGF-IR and IGF-IR/insulin
      hybrid receptor signaling in vitro and in vivo. Synergistic and additive drug
      interactions were seen for ganitumab and carboplatin or paclitaxel in vitro.
      Furthermore, ganitumab significantly increased the efficacy of cisplatin in
      ovarian cancer xenograft models in vivo. CONCLUSIONS: These observations provide
      a biologic rationale to test ganitumab as a single agent or in combination with
      carboplatin/cisplatin and paclitaxel in patients with ovarian cancer. Moreover,
      assessment of tumor expression of IGF-II, phospho-IGF-IR, or PTEN status may help
      select patients with ovarian cancer who are most likely to benefit from
      ganitumab. Clin Cancer Res; 20(11); 2947-58. (c)2014 AACR.

PMID- 24727327
TI  - Small-molecule RA-9 inhibits proteasome-associated DUBs and ovarian cancer in
      vitro and in vivo via exacerbating unfolded protein responses.
AB  - PURPOSE: Ovarian cancer is the deadliest of the gynecologic malignancies.
      Carcinogenic progression is accompanied by upregulation of ubiquitin-dependent
      protein degradation machinery as a mechanism to compensate with elevated
      endogenous proteotoxic stress. Recent studies support the notion that
      deubiquitinating enzymes (DUB) are essential factors in proteolytic degradation
      and that their aberrant activity is linked to cancer progression and
      chemoresistance. Thus, DUBs are an attractive therapeutic target for ovarian
      cancer. EXPERIMENTAL DESIGN: The potency and selectivity of RA-9 inhibitor for
      proteasome-associated DUBs was determined in ovarian cancer cell lines and
      primary cells. The anticancer activity of RA-9 and its mechanism of action were
      evaluated in multiple cancer cell lines in vitro and in vivo in immunodeficient
      mice bearing an intraperitoneal ES-2 xenograft model of human ovarian cancer.
      RESULTS: Here, we report the characterization of RA-9 as a small-molecule
      inhibitor of proteasome-associated DUBs. Treatment with RA-9 selectively induces
      onset of apoptosis in ovarian cancer cell lines and primary cultures derived from
      donors. Loss of cell viability following RA-9 exposure is associated with an
      unfolded protein response as mechanism to compensate for unsustainable levels of
      proteotoxic stress. In vivo treatment with RA-9 retards tumor growth, increases
      overall survival, and was well tolerated by the host. CONCLUSIONS: Our
      preclinical studies support further evaluation of RA-9 as an ovarian cancer
      therapeutic.

PMID- 24727328
TI  - Pattern of CD14+ follicular dendritic cells and PD1+ T cells independently
      predicts time to transformation in follicular lymphoma.
AB  - PURPOSE: Transformation of follicular lymphoma is a critical event associated
      with a poor prognosis. The role of the tumor microenvironment in previous
      transformation studies has yielded conflicting results. EXPERIMENTAL DESIGN: To
      define cell subtypes associated with transformation, we examined tissue specimens
      at diagnosis from patients with follicular lymphoma that later transformed and,
      using immunohistochemistry (IHC), stained for CD68, CD11c, CD21, CXCL13, FOXP3,
      PD1, and CD14. Cell content and the pattern of expression were evaluated. Those
      identified as significantly associated with time to transformation (TTT) and
      overall survival (OS) were further characterized by flow cytometry and multicolor
      IHC. RESULTS: Of note, 58 patients were analyzed with median TTT of 4.7 years.
      The pattern of PD1(+) and CD14(+) cells rather than the quantity of cells was
      predictive of clinical outcomes. On multivariate analysis, including the
      follicular lymphoma international prognostic index score, CD14(+) cells localized
      in the follicle were associated with a shorter TTT (HR, 3.0; P = 0.004). PD1(+)
      cells with diffuse staining were associated with a shorter TTT (HR, 1.9; P =
      0.045) and inferior OS (HR, 2.5; P = 0.012). Multicolor IHC and flow cytometry
      identified CD14(+) cells as follicular dendritic cells (FDC), whereas PD1(+)
      cells represented two separate populations, TFH and exhausted T cells.
      CONCLUSION: These results identify the presence of PD1(+) T cells and CD14(+) FDC
      as independent predictors of transformation in follicular lymphoma. Clin Cancer
      Res; 20(11); 2862-72. (c)2014 AACR.

PMID- 24727330
TI  - High serum level of antithymocyte globulin immediately before graft infusion is
      associated with a low likelihood of chronic, but not acute, graft-versus-host
      disease.
AB  - Rabbit antithymocyte globulin (ATG) is administered during transplant
      conditioning to decrease the risk of both acute graft-versus-host disease (aGVHD)
      and chronic graft-versus-host disease (cGVHD). Here we evaluated the relationship
      between the serum concentration of ATG (capable of binding to lymphocytes)
      immediately before graft infusion (day 0) or on day +7 or +28 post
      transplantation and the development of aGVHD or cGVHD. We studied 180 patients
      whose conditioning included 4.5 mg/kg antithymocyte globulin (ATG;
      Thymoglobulin). For aGVHD, we found no association with ATG levels on day 0.
      Nevertheless, high day +7 and +28 ATG levels were associated with a low
      likelihood of aGVHD. For cGVHD, high ATG levels at all 3 time points (days 0, +7,
      and +28) were associated with a low likelihood of cGVHD. In conclusion, high-dose
      ATG administration at the time of graft infusion appears to inhibit the
      development of cGVHD, but not aGVHD; however, higher ATG levels on days +7 and
      +28 are associated with lower rates of both aGVHD and cGVHD. 

PMID- 24727331
TI  - The optimal donor source for acute myeloid leukemia: do we know the answer?

PMID- 24727329
TI  - Erlotinib, erlotinib-sulindac versus placebo: a randomized, double-blind, placebo
      controlled window trial in operable head and neck cancer.
AB  - PURPOSE: The EGF receptor (EGFR) and COX2 pathways are upregulated in head and
      neck squamous cell carcinoma (HNSCC). Preclinical models indicate synergistic
      antitumor activity from dual blockade. We conducted a randomized, double-blind,
      placebo-controlled window trial of erlotinib, an EGFR inhibitor; erlotinib plus
      sulindac, a nonselective COX inhibitor; versus placebo. EXPERIMENTAL DESIGN:
      Patients with untreated, operable stage II-IVb HNSCC were randomized 5:5:3 to
      erlotinib, erlotinib-sulindac, or placebo. Tumor specimens were collected before
      and after seven to 14 days of treatment. The primary endpoint was change in Ki67
      proliferation index. We hypothesized an ordering effect in Ki67 reduction:
      erlotinib-sulindac > erlotinib > placebo. We evaluated tissue microarrays by
      immunohistochemistry for pharmacodynamic modulation of EGFR and COX2 signaling
      intermediates. RESULTS: From 2005-2009, 47 patients were randomized for the
      target 39 evaluable patients. Thirty-four tumor pairs were of sufficient quality
      to assess biomarker modulation. Ki67 was significantly decreased by erlotinib or
      erlotinib-sulindac (omnibus comparison, two-sided Kruskal-Wallis, P = 0.04).
      Wilcoxon pairwise contrasts confirmed greater Ki67 effect in both erlotinib
      groups (erlotinib-sulindac vs. placebo, P = 0.043; erlotinib vs. placebo, P =
      0.027). There was a significant trend in ordering of Ki67 reduction: erlotinib
      sulindac > erlotinib > placebo (two-sided exact Jonckheere-Terpstra, P = 0.0185).
      Low baseline pSrc correlated with greater Ki67 reduction (R(2) = 0.312, P =
      0.024). CONCLUSIONS: Brief treatment with erlotinib significantly decreased
      proliferation in HNSCC, with additive effect from sulindac. Efficacy studies of
      dual EGFR-COX inhibition are justified. pSrc is a potential resistance biomarker
      for anti-EGFR therapy, and warrants investigation as a molecular target.

PMID- 24727332
TI  - Increasing chimerism after allogeneic stem cell transplantation is associated
      with longer survival time.
AB  - Donor chimerism after allogeneic stem cell transplantation (allo-SCT) is commonly
      used to predict overall survival (OS) and disease-free survival (DFS). Because
      chimerism is observed at 1 or more times after allo-SCT and not at baseline, if
      chimerism is in fact associated with OS or DFS, then the occurrence of either
      disease progression or death informatively censors (terminates) the observed
      chimerism process. This violates the assumptions underlying standard statistical
      regression methods for survival analysis, which may lead to biased conclusions.
      To assess the association between the longitudinal post-allo-SCT donor chimerism
      process and OS or DFS, we analyzed data from 195 patients with acute myelogenous
      leukemia (n = 157) or myelodysplastic syndrome (n = 38) who achieved complete
      remission after allo-SCT following a reduced-toxicity conditioning regimen of
      fludarabine/intravenous busulfan. Median follow-up was 31 months (range, 1.1 to
      105 months). Fitted joint longitudinal-survival time models showed that a binary
      indicator of complete (100%) donor chimerism and increasing percent of donor T
      cells were significantly associated with longer OS, whereas decreasing percent of
      donor T cells was highly significantly associated with shorter OS. Our analyses
      illustrate the usefulness of modeling repeated post-allo-SCT chimerism
      measurements as individual longitudinal processes jointly with OS and DFS to
      estimate their relationships. 

PMID- 24727333
TI  - Randomized double-blind clinical trial comparing clobetasol and dexamethasone for
      the topical treatment of symptomatic oral chronic graft-versus-host disease.
AB  - Patients who undergo allogeneic stem cell transplantation frequently develop an
      immunologic disease caused by the reactivation of the graft to the host tissues.
      This disease is called graft-versus-host disease (GVHD) and it is usually a
      systemic disorder. In a large proportion of cases, oral disorders that are
      related to a chronic phase of GVHD (cGVHD) occur, and their treatment involves
      the use of topical immunosuppressive drugs. Several medications have been studied
      for this purpose, but only a small number of clinical trials have been published.
      The present study is a randomized, double-blind clinical trial that compares
      topical clobetasol and dexamethasone for the treatment of symptomatic oral cGVHD.
      Patients were randomly assigned to treatment with clobetasol propionate .05% or
      dexamethasone .1 mg/mL for 28 days. In both arms, nystatin 100,000 IU/mL was
      administered with the corticosteroid. Oral lesions were evaluated by the modified
      oral mucositis rating scale (mOMRS) and symptoms were registered using a visual
      analogue scale. Thirty-five patients were recruited, and 32 patients were
      randomized into the study groups: 18 patients (56.3%) to the dexamethasone group
      and 14 patients (43.8%) to the clobetasol group. The use of clobetasol resulted
      in a significant reduction in mOMRS total score (P = .04) and in the score for
      ulcers (P = .03). In both groups, there was significant symptomatic improvement
      but the response was significantly greater in the clobetasol group (P = .02). In
      conclusion, clobetasol was significantly more effective than dexamethasone for
      the amelioration of symptoms and clinical aspects of oral lesions in cGVHD. 

PMID- 24727334
TI  - Outcomes of lung transplantation after allogeneic hematopoietic stem cell
      transplantation.
AB  - Other than lung transplantation (LT), no specific therapies exist for end-stage
      lung disease resulting from hematopoietic stem cell transplantation (HCT)-related
      complications, such as bronchiolitis obliterans syndrome (BOS). We report the
      indications and outcomes in patients who underwent LT after HCT for hematologic
      disease from a retrospective case series at our institution and a review of the
      medical literature. We identified a total of 70 cases of LT after HCT, including
      9 allogeneic HCT recipients from our institution who underwent LT between 1990
      and 2010. In our cohort, the median age was 16 years (range, 10 to 35 years) at
      the time of HCT and 34 years (range, 17 to 44 years) at the time of LT, with a
      median interval between HCT and LT of 10 years (range, 2.9 to 27 years).
      Indications for LT-included pulmonary fibrosis (n = 4), BOS (n = 3), interstitial
      pneumonitis related to graft-versus-host disease (GVHD) (n = 1), and primary
      pulmonary hypertension (n = 1). Median survival was 49 months (range, 2 weeks to
      87 months), and 1 patient remains alive at more than 3 years after LT. Survival
      at 1 year and 5 years after LT was 89% and 37%, respectively. In the medical
      literature between 1992 and July 2013, we identified 20 articles describing 61
      cases of LT after HCT from various centers in the United States, Europe, and
      Asia. Twenty-six of the 61 cases (43%) involved patients age <18 years at the
      time of LT. BOS and GVHD of the lung were cited as the indication for LT in the
      majority of cases (80%; n = 49), followed by pulmonary fibrosis and interstitial
      lung disease (20%; n = 12). In publications reporting 3 or more cases with a
      follow-up interval ranging from the immediate postoperative period to 16 years,
      the survival rate was 71% (39 of 55). Most deaths were attributed to long-term
      complications of the lung allograft, including infections and BOS. Two deaths
      were related to recurrent or relapsed hematologic malignancy. LT can prolong
      survival in some patients who suffer from end-stage pulmonary complications after
      HCT. Patient factors that likely improve the chances of a good long-term outcome
      include young age, at least 2 years post-HCT free of relapse from the original
      hematologic malignancy, and lack of other end-organ dysfunction or manifestations
      of chronic GVHD that require treatment with immunosuppressive agents. 

PMID- 24727335
TI  - Comparable long-term outcome of unrelated cord blood transplantation with related
      bone marrow or peripheral blood stem cell transplantation in patients aged 45
      years or older with hematologic malignancies after myeloablative conditioning.
AB  - We investigated whether bone marrow or peripheral blood stem cells from older
      sibling donors or cord blood from unrelated donors provided a better outcome in
      allogeneic hematopoietic stem cell transplantation for relatively older patients
      who were candidates for myeloablative conditioning. Clinical outcomes of 97
      patients aged 45 years or older with hematologic malignancies who received
      unrelated cord blood transplantation (CBT) (n = 66) or bone marrow
      transplantation (BMT) or peripheral blood stem cell transplantation (PBSCT) from
      related donors (n = 31) were compared. The cumulative incidences of grades III to
      IV acute and extensive chronic graft-versus-host diseases were similar between
      both groups. Although transplant-related mortality was significantly lower after
      CBT compared with BMT/PBSCT from related donors (hazard ratio [HR], .29, P =
      .04), overall mortality (HR, .72, P = .47) and relapse (HR, 2.02, P = .23) were
      not significantly different after CBT and BMT/PBSCT from related donors. These
      data suggest that CBT could be as safe and effective as BMT/PBSCT from older
      related donors for relatively older patients when it is used as a primary
      unrelated stem cell source. 

PMID- 24727336
TI  - Bloodstream infection after stem cell transplantation in children with idiopathic
      aplastic anemia.
AB  - Bloodstream infection (BSI) is the most common infectious complication of
      hematopoietic stem cell transplantation (HSCT) and can cause substantial
      morbidity and mortality. Identification of risk factors for BSI might be helpful
      in efforts to reduce transplantation-related death. This study analyzed the
      incidence of BSI and risk factors for BSI after HSCT in pediatric patients with
      aplastic anemia (AA). BSI occurred in 39 of the 351 patients with AA (11.1%).
      Onset of BSI occurred at a median of 8 days after HSCT (range, 0 to 92 days). The
      5-year overall survival rate was lower in patients with BSI than in patients
      without BSI (63.32% +/- 7.90% versus 93.35% +/- 1.44%; P < .0001). Univariate
      analysis identified the following variables as associated with BSI: history of
      immunosuppressive therapy with antithymocyte globulin (ATG), transplantation from
      an unrelated donor, frequent blood transfusion before transplantation, major or
      major plus minor ABO type mismatch, graft-versus-host disease prophylaxis with
      tacrolimus and without cyclosporine, and long interval from diagnosis to
      transplantation. Among these factors, long interval from diagnosis to
      transplantation was the sole statistically significant risk factor for BSI on
      multivariate analysis. In patients who underwent HSCT from a related donor, age
      >=14 years at transplantation was risk factor for BSI. In contrast, history of
      immunosuppressive therapy with ATG, frequent blood transfusion before HSCT, graft
      failure, and major or major plus minor ABO type mismatch were risk factors for
      BSI in patients who underwent HSCT from an unrelated donor. Because the overall 5
      year survival rate without BSI was >90%, even in patients who were received a
      transplant from an unrelated donor, control of BSI is very important for
      successful HSCT in pediatric patients with AA. 

PMID- 24727337
TI  - Pharmacokinetic and pharmacodynamic analysis of inosine monophosphate
      dehydrogenase activity in hematopoietic cell transplantation recipients treated
      with mycophenolate mofetil.
AB  - A novel approach to personalizing postgrafting immunosuppression in hematopoietic
      cell transplantation (HCT) recipients is evaluating inosine monophosphate
      dehydrogenase (IMPDH) activity as a drug-specific biomarker of mycophenolic acid
      (MPA)-induced immunosuppression. This prospective study evaluated total MPA,
      unbound MPA, and total MPA glucuronide plasma concentrations and IMPDH activity
      in peripheral blood mononuclear cells (PMNCs) at 5 time points after the morning
      dose of oral mycophenolate mofetil (MMF) on day +21 in 56 nonmyeloablative HCT
      recipients. Substantial interpatient variability in pharmacokinetics and
      pharmacodynamics was observed and accurately characterized by the population
      pharmacokinetic-dynamic model. IMPDH activity decreased with increasing MPA
      plasma concentration, with maximum inhibition coinciding with maximum MPA
      concentration in most patients. The overall relationship between MPA
      concentration and IMPDH activity was described by a direct inhibitory maximum
      effect model with an IC50 of 3.23 mg/L total MPA and 57.3 ng/mL unbound MPA. The
      day +21 IMPDH area under the effect curve (AUEC) was associated with
      cytomegalovirus reactivation, nonrelapse mortality, and overall mortality. In
      conclusion, a pharmacokinetic-dynamic model was developed that relates plasma MPA
      concentrations with PMNC IMPDH activity after an MMF dose in HCT recipients.
      Future studies should validate this model and confirm that day +21 IMPDH AUEC is
      a predictive biomarker. 

PMID- 24727338
TI  - Circadian rhythm disruption by a novel running wheel: roles of exercise and
      arousal in blockade of the luteinizing hormone surge.
AB  - Exposure of proestrous Syrian hamsters to a new room, cage, and novel running
      wheel blocks the luteinizing hormone (LH) surge until the next day in ~75% of
      hamsters [1]. The studies described here tested the hypotheses that 1) exercise
      and/or 2) orexinergic neurotransmission mediate novel wheel blockade of the LH
      surge and circadian phase advances. Female hamsters were exposed to a 14L:10D
      photoperiod and activity rhythms were monitored with infra-red detectors. In
      Expt. 1, to test the effect of exercise, hamsters received jugular cannulae and
      on the next day, proestrus (Day 1), shortly before zeitgeber time 5 (ZT 5, 7h
      before lights-off) the hamsters were transported to the laboratory. After
      obtaining a blood sample at ZT 5, the hamsters were transferred to a new cage
      with a novel wheel that was either freely rotating (unlocked), or locked until ZT
      9, and exposed to constant darkness (DD). Blood samples were collected hourly for
      2days from ZT 5-11 under red light for determination of plasma LH levels by
      radioimmunoassay. Running rhythms were monitored continuously for the next 10
      14days. The locked wheels were as effective as unlocked wheels in blocking LH
      surges (no Day 1 LH surge in 6/9 versus 8/8 hamsters, P>0.05) and phase advances
      in the activity rhythms did not differ between the groups (P=0.28), suggesting
      that intense exercise is not essential for novel wheel blockade and phase advance
      of the proestrous LH surge. Expt. 2 tested whether orexin neurotransmission is
      essential for these effects. Hamsters were treated the same as those in Expt. 1
      except that they were injected (i.p.) at ZT 4.5 and 5 with either the orexin 1
      receptor antagonist SB334867 (15mg/kg per injection) or vehicle (25% DMSO in 2
      hydroxypropyl-beta-cyclodextrin (HCD)). SB-334867 inhibited novel wheel blockade
      of the LH surge (surges blocked in 2/6 SB334867-injected animals versus 16/18
      vehicle-injected animals, P<0.02) and also inhibited wheel running and circadian
      phase shifts, indicating that activation of orexin 1 receptors is necessary for
      these effects. Expt. 3 tested the hypothesis that novel wheel exposure activates
      orexin neurons. Proestrous hamsters were transferred at ZT 5 to a nearby room
      within the animal facility and were exposed to a new cage with a locked or
      unlocked novel wheel or left in their home cages. At ZT 8, the hamsters were
      anesthetized, blood was withdrawn, they were perfused with fixative and brains
      were removed for immunohistochemical localization of Fos, GnRH, and orexin.
      Exposure to a wheel, whether locked or unlocked, suppressed circulating LH
      concentrations at ZT 8, decreased the proportion of Fos-activated GnRH neurons,
      and increased Fos-immunoreactive orexin cells. Unlocked wheels had greater
      effects than locked wheels on all three endpoints. Thus in a familiar
      environment, exercise potentiated the effect of the novel wheel on Fos expression
      because a locked wheel was not a sufficient stimulus to block the LH surge. In
      conclusion, these studies indicate that novel wheel exposure activates orexin
      neurons and that blockade of orexin 1 receptors prevents novel wheel blockade of
      the LH surge. These findings are consistent with a role for both exercise and
      arousal in mediating novel wheel blockade of the LH surge. 

PMID- 24727339
TI  - Tickling during adolescence alters fear-related and cognitive behaviors in rats
      after prolonged isolation.
AB  - Social interactions during adolescence are important especially for neuronal
      development and behavior. We recently showed that positive emotions induced by
      repeated tickling could modulate fear-related behaviors and sympatho-adrenal
      stress responses. In the present study, we examined whether tickling during early
      to late adolescence stage could reverse stress vulnerability induced by socially
      isolated rearing. Ninety-five male Fischer rats were reared under different
      conditions from postnatal day (PND) 21 to 53: group-housed (three rats/cage),
      isolated-nontickled (one rat/cage) and isolated-tickled (received tickling
      stimulation for 5min a day). Auditory fear conditioning was then performed on the
      rats at PND 54. Isolated-tickled rats exhibited significantly lower freezing
      compared with group-housed rats in the first retention test performed 48h after
      conditioning and compared with isolated-nontickled rats in the second retention
      test performed 96h after conditioning. Moreover, group-housed and isolated
      tickled rats tended to show a significant decrease in freezing responses in the
      second retention test; however, isolated-nontickled rats did not. In the Morris
      water maze task that was trained in adulthood (PND 88), but not in adolescence
      (PND 56), isolated-nontickled rats showed slower decrease of escape latency
      compared to group-housed rats; however, tickling treatment significantly improved
      this deficit. These results suggest that tickling stimulation can alleviate the
      detrimental effects of isolated rearing during adolescence on fear responses and
      spatial learning. 

PMID- 24727340
TI  - Naloxone treatment alters gene expression in the mesolimbic reward system in
      'junk food' exposed offspring in a sex-specific manner but does not affect food
      preferences in adulthood.
AB  - We have previously reported that the opioid receptor blocker, naloxone, is less
      effective in reducing palatable food intake in offspring exposed to a maternal
      cafeteria diet during the perinatal period, implicating a desensitization of the
      central opioid pathway in the programming of food preferences. The present study
      aimed to investigate the effect of a maternal cafeteria diet and naloxone
      treatment on the development of the mesolimbic reward pathway and food choices in
      adulthood. We measured mRNA expression of key components of the reward pathway
      (mu-opioid receptor, proenkephalin, tyrosine hydroxylase, D1 and D2 receptors and
      the dopamine active transporter (DAT)) in the nucleus accumbens (NAc) and ventral
      tegmental area (VTA) of the offspring of control and cafeteria fed (JF) dams at
      weaning and after a 10-day naloxone treatment post-weaning and determined food
      preferences in adulthood in the remaining offspring. Naloxone treatment decreased
      the expression of DAT by 8.2 fold in female control offspring but increased it by
      4.3 fold in female offspring of JF dams relative to the saline-injected reference
      groups. Proenkephalin mRNA expression was higher in the NAc of female JF
      offspring compared to controls, independent of naloxone treatment (P<0.05). There
      was no effect of naloxone treatment on food preferences in adulthood in either
      control or JF offspring. These data indicate that prenatal exposure to a
      cafeteria diet alters the impact of opioid signaling blockade in the early post
      weaning period on gene expression in the central reward pathway in a sex specific
      manner, but that these changes in gene expression do not appear to have any
      persistent impact on food preferences in adulthood. 

PMID- 24727341
TI  - Attentional modulation by reward and punishment cues in relation to depressive
      symptoms.
AB  - BACKGROUND AND OBJECTIVES: Research indicates that individuals at-risk for
      depression are characterized by high sensitivity to loss and reduced sensitivity
      to reward. Moreover, it has been shown that attentional bias plays an important
      role in depression vulnerability. The current study aimed to examine the
      interplay between these risk factors for depression by examining the development
      of attentional bias toward reward and loss signals in dysphoric participants
      (individuals with elevated levels of depressive symptoms). METHODS: Shapes were
      conditioned to reward and loss and subsequently presented in a dot probe task in
      a sample of dysphoric and nondysphoric participants. RESULTS: Nondysphoric
      individuals oriented towards reward-related signals whereas dysphoric individuals
      failed to develop a reward-related attentional bias. This attentional effect was
      observed in the absence of group differences in motivational factors. No group
      differences were found for attentional bias for loss-related signals, despite the
      fact that dysphoric individuals performed worse in response to losing.
      LIMITATIONS: The current sample is not clinical thus generalization to clinical
      depression is not warranted. CONCLUSIONS: We argue that impaired early
      attentional processing of rewards are an important cognitive risk factor for
      anhedonic symptoms in persons with dysphoria.

PMID- 24727342
TI  - Emotion regulation, physiological arousal and PTSD symptoms in trauma-exposed
      individuals.
AB  - OBJECTIVES: Retrospective studies suggest a link between PTSD and difficulty
      regulating negative emotions. This study investigated the relationship between
      PTSD symptoms and the ability to regulate negative emotions in real-time using a
      computerised task to assess emotion regulation. METHOD: Trauma-exposed ambulance
      workers (N = 45) completed self-report measures of trauma exposure, PTSD symptoms
      and depression. Participants then completed a computer task requiring them to
      enhance, decrease or maintain their negative emotions in response to unpleasant
      images. Skin conductance responses (SCR) were recorded and participants also made
      ratings of emotion intensity. Immediately after the computer task, participants
      were asked to describe the strategies they had used to regulate their negative
      emotions during the task and recorded spontaneous intrusions for the unpleasant
      images they had seen throughout the following week. RESULTS: PTSD symptoms were
      associated with difficulty regulating (specifically, enhancing) negative
      emotions, greater use of response modulation (i.e., suppression) and less use of
      cognitive change (i.e., reappraisal) strategies to down-regulate their negative
      emotions during the task. More intrusions developed in participants who had
      greater reductions in physiological arousal whilst decreasing their negative
      emotions. LIMITATIONS: PTSD was measured by self-report rather than by a
      clinician administered interview. The results suggest a relationship between
      emotion regulation ability and PTSD symptoms rather than emotion regulation and
      PTSD. CONCLUSIONS: Difficulty regulating negative emotions may be a feature of
      trauma-exposed individuals with PTSD symptoms, which may be linked to the types
      of strategies they employ to regulate negative emotions.

PMID- 24727343
TI  - Testing the degradation effects of three reagents on various antineoplastic
      compounds.
AB  - OBJECTIVE: Studies for decontamination of antineoplastic compounds have been
      conducted for decades. Nevertheless, recent studies indicate the contamination of
      work place in hospitals, and the exposure of workers. In this study, to develop
      an effective cleaning method for contaminated environments, the degradation
      efficacies of antineoplastic compounds by reagents were evaluated. METHODS: The
      degradation efficacies of various combinations of three reagents (sodium
      hypochlorite, sodium thiosulfate, and sodium hydroxide) were evaluated with four
      antineoplastic compounds (cyclophosphamide, epirubicin, cisplatin, and
      carboplatin). The residues of antineoplastic compounds were measured with high
      performance liquid chromatography. RESULTS: Of the three reagents, sodium
      hypochlorite was the most effective to all antineoplastic compounds used in this
      study. Although sodium hypochlorite degraded 86.6% of cyclophosphamide, it
      degraded other three antineoplastic compounds completely. The combination with
      sodium hypochlorite and sodium thiosulfate degraded only 3.3% of
      cyclophosphamide, since sodium thiosulfate inhibited the degradation ability of
      sodium hypochlorite. Similarly, the combinations used in all three reagents
      failed to degrade cyclophosphamide. CONCLUSION: Although three of four
      antineoplastic compounds were degraded successfully, any combinations of three
      reagents could not degrade cyclophosphamide completely. However, the addition of
      sodium thiosulfate which inhibits the corrosion of metal by sodium hypochlorite
      is essential for daily cleaning. Therefore, the evaluation of reaction time
      before the addition of sodium thiosulfate may be required. We will continue to
      investigate the reagents for degradation.

PMID- 24727344
TI  - Claims analysis of hypertension occurrence, severity changes and patterns of
      antihypertensive use in cancer patients receiving vascular endothelial growth
      factor inhibitors.
AB  - BACKGROUND: Vascular endothelial growth factor inhibitors such as bevacizumab,
      sorafenib, and sunitinib are utilized in the treatment of multiple cancers.
      Although these agents are associated with hypertension, there is a lack of
      evidence describing patterns of antihypertensive use in patients with vascular
      endothelial growth factor inhibitor-associated hypertension in a non-trial, "real
      world" setting. OBJECTIVE: To describe the occurrence and severity of vascular
      endothelial growth factor inhibitor-associated hypertension, patterns of
      antihypertensive use and occurrence of cardiovascular complications in a non
      trial population, and to describe patterns of initial antihypertensive therapy in
      patients developing hypertension during treatment with a vascular endothelial
      growth factor inhibitor. METHODS: This retrospective cohort study utilized claims
      data from the Medstat MarketScan Commercial Claims and Encounter database to
      identify patients with claims for a vascular endothelial growth factor inhibitor
      and a diagnosis of cancer using International Classification of Diseases, 9th
      Revision, Clinical Modification codes, Healthcare Common Procedure Coding System
      J-codes and National Drug Codes. The study period encompassed claims from one
      year before the patient's first claim for a vascular endothelial growth factor
      inhibitor, and continued through one year after the initial vascular endothelial
      growth factor inhibitor claim. Patients meeting study criteria were classified
      into cohorts A1, patients with no hypertension throughout the study period; A2,
      patients without hypertension at baseline who developed hypertension after
      starting a vascular endothelial growth factor inhibitor; and cohort B, patients
      with hypertension prior to receiving a vascular endothelial growth factor
      inhibitor. We utilized medical and pharmacy claims data to describe the presence
      of hypertension, its severity, and the occurrence of cardiovascular complications
      throughout the study period. Initial antihypertensive use in cohort A2 was
      described. RESULTS: In all, 2177 patients met study criteria and were categorized
      into cohorts A1 (n = 708), A2 (n = 333) and B (n = 1136). Approximately 32% of
      patients without hypertension at baseline had claims suggestive for hypertension
      during the study period. Life-threatening (Grade 4) hypertension increased
      throughout the study period for cohorts A1, A2, and B, to 3.4%, 10.2%, and 16.4%,
      respectively (p < 0.001 for all). Claims suggestive of Grade 3 hypertension
      occurred in more patients in cohort B (45.8%) than in cohort A2 (32.7%, p <
      0.001). Cardiovascular complications occurred in 4.7%, 15.6%, and 22.7% of
      patients in cohorts A1, A2, and B, respectively. Initial antihypertensive agent
      selection did not impact the occurrence of cardiovascular complications in cohort
      A2. CONCLUSION: Our study provides valuable insight into non-trial patterns of
      vascular endothelial growth factor inhibitor-associated hypertension occurrence
      and severity, and is consistent with prior claims analysis. Identification of
      optimal strategies to manage vascular endothelial growth factor inhibitor
      associated hypertension remain to be clarified with the advent of more
      comprehensive data sets.

PMID- 24727345
TI  - Interdisciplinary rehabilitation of patients with chronic widespread pain:
      primary endpoint of the randomized, nonblinded, parallel-group IMPROvE trial.
AB  - This study examined the functional and psychological outcomes of a 2-week, group
      based multicomponent treatment course that targeted patients with chronic
      widespread pain. Patients (192 included in the intention-to-treat population),
      all fulfilling the 1990 American College of Rheumatology classification criteria
      for fibromyalgia, were consecutively recruited from a tertiary care setting and
      randomized (1:1) to either the treatment course or a waiting list control group.
      Co-primary outcomes were the Assessment of Motor and Process Skills (AMPS) and SF
      36 Mental Composite Score (MCS) evaluated at 6-month follow-up. Primary endpoints
      were partly achieved with a statistically significant improvement in AMPS
      activities of daily living motor (group mean difference: 0.20 [95% confidence
      interval (CI): 0.09 to 0.31] logits; P=.0003) and AMPS activities of daily living
      process (0.20 [95% CI: 0.12 to 0.27] logits, P<.0001) ability measures, whereas
      no difference in the SF-36 MCS (1.14 [95% CI: -1.52 to 3.81], P=.40) was
      observed. Individual patient responses varied, and the proportion of patients
      achieving a clinically meaningful change of at least 0.3 logits on the AMPS
      seemed influenced by the reporting of a pending social welfare application at the
      time of enrollment. We conclude that even in fibromyalgia patients presenting
      with a substantial disability established over many years, the 2-week
      multicomponent treatment course resulted in observable improvement of functional
      ability in a subgroup of patients at 6-month follow-up. This improvement,
      however, was not reflected in secondary patient reported outcomes, including
      scores of self-reported functional ability on standardized questionnaires. We
      suggest including observation-based assessments in future clinical trials
      focusing on functional outcomes in patients with fibromyalgia. 

PMID- 24727347
TI  - Analgesic drug consumption increases after knee arthroplasty: a
      pharmacoepidemiological study investigating postoperative pain.
AB  - Knee arthroplasty remains the gold standard in the treatment of severe
      osteoarthritis. Chronic postoperative pain has been reported with a prevalence
      ranging from 15% to 47%. The aim of this study was to compare analgesic drug
      consumption before and after surgery as an indicator of pain after knee surgery.
      A pharmacoepidemiological method comparing analgesics and antineuropathic issues
      1 year before and 1 year after surgery was used. All patients who underwent knee
      arthroplasty in the Midi-Pyrenees region (2.5 million inhabitants) were
      identified through the Health Insurance System Database. Increase of drug issues
      (all analgesics, antineuropathic drugs, strong opioids) was calculated and
      compared between several periods surrounding the surgery (12 months, 2 months,
      and 10 months before and after the knee arthroplasty). A multivariate logistic
      regression model was used to identify factors associated with chronic
      postoperative pain. The study included 1939 patients. An increase in analgesic,
      antineuropathic, and opioid drug consumption was observed the year after the
      surgery in 47.3%, 8.6%, and 5.6% of patients, respectively. Multivariate analysis
      found a significant association between type of surgery (total knee vs
      unicompartmental arthroplasty) and analgesic consumption 1 year after surgery,
      and between preoperative pain and psychiatric vulnerability and increase in
      neuropathic drug dispensing. Conversely, older age was considered as a protective
      factor. This study revealed that an increase in the issue of different analgesic
      drugs is present in half of patients 1 year after knee arthroplasty. Several
      associated factors of drug consumption (preoperative pain, type of surgery, and
      psychiatric disorder) were identified.

PMID- 24727346
TI  - beta2- and beta3-adrenergic receptors drive COMT-dependent pain by increasing
      production of nitric oxide and cytokines.
AB  - Decreased activity of catechol-O-methyltransferase (COMT), an enzyme that
      metabolizes catecholamines, contributes to pain in humans and animals.
      Previously, we demonstrated that development of COMT-dependent pain is mediated
      by both beta2- and beta3-adrenergic receptors (beta2ARs and beta3ARs). Here we
      investigated molecules downstream of beta2- and beta3ARs driving pain in animals
      with decreased COMT activity. Based on evidence linking their role in pain and
      synthesis downstream of beta2- and beta3AR stimulation, we hypothesized that
      nitric oxide (NO) and proinflammatory cytokines drive COMT-dependent pain. To
      test this, we measured plasma NO derivatives and cytokines in rats receiving the
      COMT inhibitor OR486 in the presence or absence of the beta2AR antagonist
      ICI118,551+beta3AR antagonist SR59320A. We also assessed whether the NO synthase
      inhibitor L-N(G)-nitroarginine methyl ester (L-NAME) and cytokine-neutralizing
      antibodies block the development of COMT-dependent pain. Results showed that
      animals receiving OR486 exhibited higher levels of NO derivatives, tumor necrosis
      factor alpha (TNFalpha), interleukin-1beta (IL-1beta), interleukin-6 (IL-6), and
      chemokine (C-C motif) ligand 2 (CCL2) in a beta2- and beta3AR-dependent manner.
      Additionally, inhibition of NO synthases and neutralization of the innate
      immunity cytokines TNFalpha, IL-1beta, and IL-6 blocked the development of COMT
      dependent pain. Finally, we found that NO influences TNFalpha, IL-1beta, IL-6,
      and CCL2 levels, whereas TNFalpha and IL-6 influence NO levels. Altogether, these
      results demonstrate that beta2- and beta3ARs contribute to COMT-dependent pain,
      at least partly, by increasing NO and cytokines. Furthermore, they identify beta2
      and beta3ARs, NO, and proinflammatory cytokines as potential therapeutic targets
      for pain patients with abnormalities in COMT physiology.

PMID- 24727348
TI  - Does liberalizing cannabis laws increase cannabis use?
AB  - A key question in the ongoing policy debate over cannabis' legal status is
      whether liberalizing cannabis laws leads to an increase in cannabis use. This
      paper provides new evidence on the impact of a specific type of liberalization,
      decriminalization, on initiation into cannabis use. Our identification strategy
      exploits variation in the timing of cannabis policy reforms and our estimation
      framework marries a difference-in-difference approach with a discrete time
      duration model. Our results reveal evidence of both heterogeneity and dynamics in
      the response of cannabis uptake to decriminalization. Overall, we find that the
      impact of decriminalization is concentrated amongst minors, who have a higher
      rate of uptake in the first five years following its introduction. 

PMID- 24727351
TI  - Colorimetric detection of melamine in milk by citrate-stabilized gold
      nanoparticles.
AB  - Here, we report a simple and sensitive colorimetric method for detection of
      melamine in milk using gold nanoparticles (AuNPs). AuNPs of 21-nm size were
      synthesized by the citrate reduction method. The method is based on the principle
      that the melamine causes the aggregation of AuNPs and, hence, the wine red color
      of AuNPs changes to blue or purple. This change in color can be visualized with
      the naked eye or an ultraviolet-visible (UV-Vis) spectrometer. Under optimized
      conditions, AuNPs are highly specific for melamine and can detect melamine down
      to a concentration of 0.05 mg L(-1).

PMID- 24727352
TI  - Profiling and classification of illicit heroin by ICP-MS analysis of inorganic
      elements.
AB  - Nineteen inorganic elements (Ag, As, Ba, Cd, Co, Cr, Cu, Mn, Mo, Ni, P, Pb, Se,
      Sb, Th, Tl, U, V and Zn) in heroin samples were determined using inductive
      coupled plasma mass spectrometry (ICP-MS). After Wilcoxon-Mann-Whitney test and
      correlation analysis, 10 element contents (P, V, Cr, Ni, Cu, Zn, As, Se, Pb, U)
      and 7 element ratios (U/Ba, Ba/Pb, Cd/Mn, Co/Ni, V/Cr, P/V, Cd/V) were found to
      be evidently different between heroin samples from "Golden Crescent" and "Golden
      Triangle". Based on the data set of these 17 variables in 150 authentic heroin
      samples, classification of origins was successfully achieved utilizing principal
      component analysis (PCA) and partial least squares discriminant analysis (PLS
      DA). By comparison experiment on 907 unknown samples, the developed discriminant
      model was proven to be consistent with the widely used organic profiling method,
      and meanwhile the time consumed per sample was markedly saved, which facilitates
      high throughput screening in routine analysis. 

PMID- 24727349
TI  - Role of non-receptor protein tyrosine kinases in spermatid transport during
      spermatogenesis.
AB  - Non-receptor protein tyrosine kinases are cytoplasmic kinases that activate
      proteins by phosphorylating tyrosine residues, which in turn affect multiple
      functions in eukaryotic cells. Herein, we focus on the role of non-receptor
      protein tyrosine kinases, most notably, FAK, c-Yes and c-Src, in the transport of
      spermatids across the seminiferous epithelium during spermatogenesis. Since
      spermatids, which are formed from spermatocytes via meiosis, are immotile haploid
      cells, they must be transported by Sertoli cells across the seminiferous
      epithelium during the epithelial cycle of spermatogenesis. Without the timely
      transport of spermatids across the epithelium, the release of sperms at
      spermiation fails to occur, leading to infertility. Thus, the molecular event
      pertinent to spermatid transport is crucial to spermatogenesis. We provide a
      critical discussion based on recent findings in this review. We also provide a
      hypothetical model on spermatid transport, and the role of non-receptor protein
      tyrosine kinases in this event. We also highlight areas of research that deserve
      attention by investigators in the field. 

PMID- 24727353
TI  - Hydrothermal conversion of urban food waste to chars for removal of textile dyes
      from contaminated waters.
AB  - Hydrothermal carbonization of urban food waste was carried out to prepare
      hydrochars for removal of Acridine Orange and Rhodamine 6G dyes from contaminated
      water. The chemical composition and microstructure properties of the synthesized
      hydrochars were investigated in details. Batch adsorption experiments revealed
      that hydrochars with lower degree of carbonization were more efficient in
      adsorption of dyes. Operational parameters such as pH and temperature had a
      strong influence on the dye uptake process. The adsorption equilibrium data
      showed excellent fit to the Langmuir isotherm. The pseudo-second-order kinetic
      model provided a better correlation for the experimental kinetic data in
      comparison to the pseudo-first-order kinetic model. Thermodynamic investigations
      suggested that dye adsorption onto hydrochars was spontaneous and endothermic.
      The mechanism of dye removal appears to be associated with physisorption. An
      artificial neural network (ANN)-based modelling was further carried out to
      predict the dye adsorption capacity of the hydrochars. 

PMID- 24727350
TI  - The role of the cytoskeleton and molecular motors in endosomal dynamics.
AB  - The endocytic pathway is essential for processes that define how cells interact
      with their environment, including receptor signalling, cell adhesion and
      migration, pathogen entry, membrane protein turnover and nutrient uptake. The
      spatial organisation of endocytic trafficking requires motor proteins that tether
      membranes or transport them along the actin and microtubule cytoskeletons.
      Microtubules, actin filaments and motor proteins also provide force to deform and
      assist in the scission of membranes, thereby facilitating endosomal sorting and
      the generation of transport intermediates. 

PMID- 24727354
TI  - Microbial lipid produced by Yarrowia lipolytica QU21 using industrial waste: a
      potential feedstock for biodiesel production.
AB  - This study aimed to evaluate the effect of medium composition and culture
      conditions on lipid content, fatty acid profile and biomass production by the
      yeast Yarrowia lipolytica QU21. Lipid production by the yeast growing on
      glycerol/(NH4)2SO4 (10%/0.1%) reached 1.48g/L (30.1% according to total cell dry
      weight). When glycerol was replaced by crude glycerol (industrial waste), the
      lipid yield was 1.27g/L, with no significant difference. Some particular fatty
      acids were found when crude glycerol was combined with fresh yeast extract (FYE,
      brewery waste), as linolenic acid (C18:3n3), eicosadienoic acid (C20:2),
      eicosatrienoic acid (C20:3n3) and eicosapentaenoic acid (C20:5n3). In addition,
      the FYE promoted an increase of more than 300% on polyunsaturated fatty acid
      content (PUFA), which is an undesirable feature for biodiesel production. The
      fatty acid composition of the oil produced by Y. lipolytica QU21 growing on crude
      glycerol/(NH4)2SO4 presented a potential use as biodiesel feedstock, with low
      PUFA content. 

PMID- 24727355
TI  - Engineered hydrochar composites for phosphorus removal/recovery: Lanthanum doped
      hydrochar prepared by hydrothermal carbonization of lanthanum pretreated rice
      straw.
AB  - Engineered hydrochar composites (EHC) were synthesized by hydrothermal
      carbonization (HTC) of lanthanum pretreated rice straw. The as-prepared composite
      with about 30% lanthanum content showed greater P removal potential than La(OH)3,
      indicating the synergistic effect of hydrochar and lanthanum in P removal. The
      adsorption results showed that EHC showed great P adsorption capacities (>50mgPg(
      1)) in the pH range of 2.5-10.5, and the presence of competing anions had little
      negative effects on P adsorption on EHC. The equilibrium time for P adsorption on
      EHC was considerably reduced under acid condition (12h) compared to alkaline
      condition (48h). The maximum adsorption capacity was 61.57mgPg(-1) according to
      Langmuir isotherms. These results suggested that EHC was highly effective in P
      adsorption in a wide range of pH and the presence of competing anions, thus EHC
      could be a promising adsorbent for phosphorus removal/recovery from wastewater. 

PMID- 24727356
TI  - Dietary pattern and its association with the prevalence of obesity, hypertension
      and other cardiovascular risk factors among Chinese older adults.
AB  - AIM: This article examined the association between dietary patterns and
      cardiovascular risk factors in Chinese older adults. METHODS: For this study,
      older adults with one or more cardiovascular risk factors or a history of
      cardiovascular disease were randomly selected using health check medical records
      from the Changshu and Beijing Fangshan Centers for Disease Control and
      Prevention. Exploratory factor analysis and cluster analysis was used to extract
      dietary pattern factors. Log binomial regression analysis was used to analyse the
      association between dietary patterns and chronic disease related risk factors.
      RESULTS: Four factors were found through factor analysis. A high level of
      internal consistency was obtained, with a high Cronbach's alpha coefficient of
      0.83. Cluster analysis identified three dietary patterns: healthy diet, Western
      diet, and balanced diet. Findings in this sample of Chinese adults correspond to
      those reported in previous studies, indicating that a Western diet is
      significantly related to likelihood of having obesity, hypertension and the
      metabolic syndrome. The identification of distinct dietary patterns among Chinese
      older adults and the nutritional status of people with chronic diseases suggest
      that the three dietary patterns have a reasonable level of discriminant validity.
      CONCLUSIONS: This study provides evidence that a FFQ is a valid and reliable tool
      to assess the dietary patterns of individuals with chronic diseases in small- to
      medium-size urban and rural settings in China. It also validates the significant
      association between dietary pattern and cardiovascular disease risk factors,
      including body mass index, blood pressure, triglycerides, and metabolic
      conditions. Clinical diagnosis of chronic disease further confirmed this
      relationship in Chinese older adults.

PMID- 24727357
TI  - Perceived stress scores among Saudi students entering universities: a prospective
      study during the first year of university life.
AB  - In this prospective study we wanted to determine whether perceived stress over
      time among students in the Preparatory Year of King Saud University (KSU)
      predisposes them to cardiometabolic abnormalities. A total of 110 apparently
      healthy Saudi students (35 men and 75 women enrolled during the 2010-2011
      academic year) were included. Perceived stress was determined at baseline and 1
      year later. Anthropometrics were obtained and morning fasting serum glucose,
      lipid profile and cortisol were measured at both times. Perceived stress was
      noted among 48.2% of subjects at baseline and was not significantly different
      after follow-up, with 45.4% scoring high. In men, the prevalence of perceived
      stress was 48.6% at baseline (13 out of 35) and 37.1% at follow-up (13 out of
      35), while in women it was 48% at baseline and 49.3% at follow-up. Interestingly,
      significant improvements in the blood pressure and lipid profiles, with the
      exception of HDL-cholesterol, were observed in both men and women, while fasting
      glucose also improved in women. Serum cortisol was inversely associated to
      fasting glucose, and total- and LDL-cholesterol (p-values 0.007, 0.04 and 0.04,
      respectively). These data are opposite to findings in students entering Western
      universities, in whom increasing stress and a deteriorating cardiometabolic
      profile have been repeatedly noted. Perceived stress and morning cortisol levels
      among students of the Preparatory Year in KSU remained constant for both genders
      over time, yet an improved cardiometabolic profile was observed, suggesting good
      adaptation among our pre-college students in their first year of university life.

PMID- 24727358
TI  - MRI to X-ray mammography intensity-based registration with simultaneous
      optimisation of pose and biomechanical transformation parameters.
AB  - Determining corresponding regions between an MRI and an X-ray mammogram is a
      clinically useful task that is challenging for radiologists due to the large
      deformation that the breast undergoes between the two image acquisitions. In this
      work we propose an intensity-based image registration framework, where the
      biomechanical transformation model parameters and the rigid-body transformation
      parameters are optimised simultaneously. Patient-specific biomechanical modelling
      of the breast derived from diagnostic, prone MRI has been previously used for
      this task. However, the high computational time associated with breast
      compression simulation using commercial packages, did not allow the optimisation
      of both pose and FEM parameters in the same framework. We use a fast explicit
      Finite Element (FE) solver that runs on a graphics card, enabling the FEM-based
      transformation model to be fully integrated into the optimisation scheme. The
      transformation model has seven degrees of freedom, which include parameters for
      both the initial rigid-body pose of the breast prior to mammographic compression,
      and those of the biomechanical model. The framework was tested on ten clinical
      cases and the results were compared against an affine transformation model,
      previously proposed for the same task. The mean registration error was 11.6+/
      3.8mm for the CC and 11+/-5.4mm for the MLO view registrations, indicating that
      this could be a useful clinical tool. 

PMID- 24727359
TI  - Systolic blood pressure and outcomes in stage 3-4 chronic kidney disease
      patients: evidence from a Taiwanese cohort.
AB  - BACKGROUND: Systolic blood pressure (SBP) goal for chronic kidney disease (CKD)
      patients is <=140mm Hg. However, the SBP target provides no suggested lower
      limit, and some studies indicate that a lower SBP target may be harmful. We aimed
      to investigate the J-shaped relationship between SBP and clinical outcomes in CKD
      patients and the factors that modify this relationship. METHODS: This prospective
      observational study enrolled 2,144 CKD stage 3-4 patients between November 2002
      and May 2009 and followed them until July 2010 or death. Patients included were
      also enrolled within the Integrated CKD Care Program for Delaying Dialysis in a
      medical center and its branch hospital. Demographic, clinical, laboratory, and
      disease variables at baseline and end of observation were measured. RESULTS: In
      diabetic CKD patients, the hazard ratio (HR) at SBP 96-110mm Hg vs. 111-120mm Hg
      was 2.52 (95% confidence interval (CI) = 1.13-5.58) for cardiovascular outcomes
      and was 3.14 (95% CI = 1.16-8.49) for renal outcomes. In nondiabetic CKD
      patients, this J-shaped relationship was not seen. Heavy proteinuria was further
      found to modify the J-shaped relationship in diabetic CKD patients. The HR for
      renal outcomes at SBP 96-110mm Hg vs. 111-120mm Hg was 4.07 (95% CI = 1.18-13.99)
      in diabetic CKD patients with heavy proteinuria vs. 1.72 (95% CI = 0.13-22.5) in
      those without heavy proteinuria. CONCLUSIONS: Diabetic CKD patients have a J
      shaped relationship between SBP and cardiovascular or renal outcomes, but
      nondiabetic CKD patients do not. The optimal SBP range might be narrower in the
      diabetic CKD patients.

PMID- 24727360
TI  - Understanding the role of embarrassment in gynaecological screening: a
      qualitative study from the ASPIRE cervical cancer screening project in Uganda.
AB  - OBJECTIVE: To define embarrassment and develop an understanding of the role of
      embarrassment in relation to cervical cancer screening and self-collected human
      papillomavirus (HPV) DNA testing in Uganda. DESIGN: Cross-sectional, qualitative
      study using semistructured one-to-one interviews and focus groups. PARTICIPANTS:
      6 key-informant health workers and 16 local women, purposively sampled. Key
      informant inclusion criteria: Ugandan members of the project team. Focus group
      inclusion criteria: woman age 30-69 years, Luganda or Swahili speaking, living or
      working in the target Ugandan community. EXCLUSION CRITERIA: unwillingness to
      sign informed consent. SETTING: Primary and tertiary low-resource setting in
      Kampala, Uganda. RESULTS: In Luganda, embarrassment relating to cervical cancer
      is described in two forms. 'Community embarrassment' describes discomfort based
      on how a person may be perceived by others. 'Personal embarrassment' relates to
      shyness or discomfort with her own genitalia. Community embarrassment was
      described in themes relating to place of study recruitment, amount of privacy in
      dwellings, personal relationship with health workers, handling of the vaginal
      swab and misunderstanding of HPV self-collection as HIV testing. Themes of
      personal embarrassment related to lack of knowledge, age and novelty of the self
      collection swab. Overall, embarrassment was a barrier to screening at the outset
      and diminished over time through education and knowledge. Fatalism regarding
      cervical cancer diagnosis, worry about results and stigma associated with a
      cervical cancer diagnosis were other psychosocial barriers described. Overcoming
      psychosocial barriers to screening can include peer-to-peer education, drama and
      media campaigns. CONCLUSIONS: Embarrassment and other psychosocial barriers may
      play a large role at the onset of a screening programme, but over time as
      education and knowledge increase, and the social norms around screening evolve,
      its role diminishes. The role of peer-to-peer education and community authorities
      on healthcare cannot be overlooked and can have a major impact in overcoming
      psychosocial and social barriers to screening.

PMID- 24727361
TI  - Database of normalised computed tomography dose index for retrospective CT
      dosimetry.
AB  - Volumetric computed tomography dose index (CTDIvol) is an important dose
      descriptor to reconstruct organ doses for patients combined with the organ dose
      calculated from computational human phantoms coupled with Monte Carlo transport
      techniques. CTDIvol can be derived from weighted CTDI (CTDIw) normalised to the
      tube current-time product (mGy/100 mAs), using knowledge of tube current-time
      product (mAs), tube potential (kVp), type of CTDI phantoms (head or body), and
      pitch. The normalised CTDIw is one of the characteristics of a CT scanner but not
      readily available from the literature. In the current study, we established a
      comprehensive database of normalised CTDIw values based on multiple data sources:
      the ImPACT dose survey from the United Kingdom, the CT-Expo dose calculation
      program, and surveys performed by the US Food and Drug Administration (FDA) and
      the National Lung Screening Trial (NLST). From the sources, the CTDIw values for
      a total of 68, 138, 30, and 13 scanner model groups were collected, respectively.
      The different scanner groups from the four data sources were sorted and merged
      into 162 scanner groups for eight manufacturers including General Electric (GE),
      Siemens, Philips, Toshiba, Elscint, Picker, Shimadzu, and Hitachi. To fill in
      missing CTDI values, a method based on exponential regression analysis was
      developed based on the existing data. Once the database was completed, two
      different analyses of data variability were performed. First, we averaged CTDI
      values for each scanner in the different data sources and analysed the
      variability of the average CTDI values across the different scanner models within
      a given manufacturer. Among the four major manufacturers, Toshiba and Philips
      showed the greatest coefficient of variation (COV) (=standard deviation/mean) for
      the head and body normalised CTDIw values, 39% and 54%, respectively. Second, the
      variation across the different data sources was analysed for CT scanners where
      more than two data sources were involved. The CTDI values for the scanners from
      Siemens showed the greatest variation across the data sources, being about four
      times greater than the variation of Toshiba scanners. The established CTDI
      database will be used for the reconstruction of CTDIvol and then the estimation
      of individualised organ doses for retrospective patient cohorts in epidemiologic
      studies. 

PMID- 24727362
TI  - Improving access to psychological therapies and older people: findings from the
      Eastern Region.
AB  - BACKGROUND: Evaluations of the Improving Access to Psychological Therapies (IAPT)
      scheme have not yet focused on minority subgroups. This paper aims to evaluate
      accessibility, waiting times and clinical outcomes of IAPT for older adults.
      METHODS: All referrals from six Primary Care Trusts (PCT) in the East of England
      were used in this analysis. During each session, the therapist recorded
      information on anxiety symptoms using the Generalised Anxiety Disorder
      Questionnaire (GAD-7) and depressive symptoms with the Patient Health
      Questionnaire (PHQ-9). Waiting times, type of referrals and reliable recovery
      rates were investigated. RESULTS: Older adults accounted for only 4% of all the
      IAPT referrals made between September 2008 and July 2010 in the Eastern Region.
      Waiting times for both IAPT assessment and treatment were slightly lower for
      older adult. In all centres, reliable recovery rates were higher in older adults
      compared to younger adults post-treatment, however these differences were not
      significant, with the exception of a difference in anxiety scores (chi(2)(1) =
      18.6, p < 0.001). In multivariate analyses, being an older adult was associated
      with recovery for depression (OR = 1.30, 95% CI 1.10-1.53), anxiety (OR = 1.42,
      95% CI 1.21-1.66), and overall recovery (OR = 1.31, 95% CI 1.10-1.54) after
      adjustment for gender, PCT region, baseline score, maximum treatment step during
      treatment, dropping out, and number of sessions. CONCLUSIONS: The IAPT services
      were shown to be beneficial to older patients, however, access to these services
      in later life has been lower than expected. The service pathway for older
      populations needs to be better researched in order to eliminate possible
      obstacles in accessing services.

PMID- 24727363
TI  - An examination of avoidance in major depression in comparison to social anxiety
      disorder.
AB  - The construct of avoidance has begun to receive attention in theoretical models
      and empirical investigations of depression. However, little is known about
      relative levels of avoidance across diagnostic categories or about the
      relationships between avoidance and other correlates of depression. The present
      study compared levels of avoidance across groups of depressed women without
      social anxiety disorder (MDD without SAD), depressed women with social anxiety
      disorder (MDD with SAD), women with social anxiety disorder (SAD), and
      nonclinical women, and investigated the relationships among avoidance, and
      sociotropy and autonomy, rumination, and negative and positive problem
      orientations within the clinically depressed group. Avoidance was found to be
      significantly higher in all clinical groups relative to the nonclinical group of
      women, and highest in the comorbid MDD with SAD group. Avoidance showed
      significant positive relationships with sociotropy, autonomy, rumination, and
      negative problem orientation, and a significant negative relationship with
      positive problem orientation within the overall sample of depressed women. These
      results suggest that avoidance should be given greater consideration in
      psychosocial models of depression and point to several important directions for
      future research. 

PMID- 24727364
TI  - Predictors and moderators of outcome for severe and enduring anorexia nervosa.
AB  - Few of the limited randomized controlled trials (RCTs) for adults with anorexia
      nervosa (AN) have explored predictors and moderators of outcome. This study aimed
      to identify predictors and moderators of outcome at end of treatment (EOT) and 6-
      and 12-month follow-up for adults with AN (N = 63). All participants met criteria
      for severe and enduring AN (duration of illness >= 7 years) and participated in
      an RCT of cognitive-behavioral therapy (CBT-AN) and specialist supportive
      clinical management (SSCM). General linear models were utilized and included all
      available outcome data at all time points. Outcome was assessed across three
      domains: eating disorder quality of life (EDQOL), mental health (MCS), and
      depressive symptoms (BDI). Predictors of better outcome included: lower age,
      shorter duration of illness, having AN-R, being employed, not taking psychotropic
      medication, and better social adjustment. Four moderators of treatment outcome
      emerged: eating disorder psychopathology (EDE Global), depression (BDI), age, and
      AN subtype. Participants with higher baseline scores on these measures, older
      age, or binge eating/purging subtype benefited more from CBT-AN than SSCM. Older
      patients with more severe eating-related psychopathology and depression have
      better outcomes in a behaviorally targeted treatment such as CBT-AN rather than a
      supportive treatment such as SSCM. 

PMID- 24727365
TI  - Obesity and neuroinflammation: a pathway to cognitive impairment.
AB  - Obesity is a growing problem worldwide and is associated with a range of
      comorbidities, including cognitive dysfunction. In this review we will address
      the evidence that obesity and high fat feeding can lead to cognitive dysfunction.
      We will also examine the idea that obesity-associated systemic inflammation leads
      to inflammation within the brain, particularly the hypothalamus, and that this is
      partially responsible for these negative cognitive outcomes. Thus, obesity, and
      high fat feeding, lead to systemic inflammation and excess circulating free fatty
      acids. Circulating cytokines, free fatty acids and immune cells reach the brain
      at the level of the hypothalamus and initiate local inflammation, including
      microglial proliferation. This local inflammation likely causes synaptic
      remodeling and neurodegeneration within the hypothalamus, altering internal
      hypothalamic circuitry and hypothalamic outputs to other brain regions. The
      result is disruption to cognitive function mediated by regions such as
      hippocampus, amygdala, and reward-processing centers. Central inflammation is
      also likely to affect these regions directly. Thus, central inflammation in
      obesity leads not just to disruption of hypothalamic satiety signals and
      perpetuation of overeating, but also to negative outcomes on cognition. 

PMID- 24727366
TI  - 'In silico expression analysis', a novel PathoPlant web tool to identify abiotic
      and biotic stress conditions associated with specific cis-regulatory sequences.
AB  - Using bioinformatics, putative cis-regulatory sequences can be easily identified
      using pattern recognition programs on promoters of specific gene sets. The
      abundance of predicted cis-sequences is a major challenge to associate these
      sequences with a possible function in gene expression regulation. To identify a
      possible function of the predicted cis-sequences, a novel web tool designated 'in
      silico expression analysis' was developed that correlates submitted cis-sequences
      with gene expression data from Arabidopsis thaliana. The web tool identifies the
      A. thaliana genes harbouring the sequence in a defined promoter region and
      compares the expression of these genes with microarray data. The result is a
      hierarchy of abiotic and biotic stress conditions to which these genes are most
      likely responsive. When testing the performance of the web tool, known cis
      regulatory sequences were submitted to the 'in silico expression analysis'
      resulting in the correct identification of the associated stress conditions. When
      using a recently identified novel elicitor-responsive sequence, a WT-box
      (CGACTTTT), the 'in silico expression analysis' predicts that genes harbouring
      this sequence in their promoter are most likely Botrytis cinerea induced.
      Consistent with this prediction, the strongest induction of a reporter gene
      harbouring this sequence in the promoter is observed with B. cinerea in
      transgenic A. thaliana. DATABASE URL:
      http://www.pathoplant.de/expression_analysis.php.

PMID- 24727367
TI  - Temporal and spatial regulation of eukaryotic DNA replication: from regulated
      initiation to genome-scale timing program.
AB  - Replication origins are where pre-replication complexes are assembled during G1
      phase. However, only a subset of the origins is actually "fired" to initiate DNA
      synthesis during S phase. Whereas factors involved in these steps are relatively
      well understood now, the mechanisms behind the origin specification, the choice
      of origins to be fired and determination of their timing are still under active
      investigation. Recent data show that the origin positions as well as the
      selection of those to be fired may be determined by multiple factors including
      sequences, chromatin context, epigenetic information, and some specific genomic
      features, but that the choice is surprisingly plastic and opportunistic. Timing
      regulation of firing, on the other hand, appears to be related to cell type
      specific intrinsic chromatin architecture in nuclei. The conserved Rif1 protein
      appears to be a major global regulator of the genome-wide replication timing.
      Replication timing is regulated also by other factors including checkpoint
      signals, local chromatin structures, timing and quantity of pre-RC formation, and
      availability of limiting initiation factors. 

PMID- 24727368
TI  - Flavin-containing monooxygenase S-oxygenation of a series of thioureas and
      thiones.
AB  - Mammalian flavin-containing monooxygenase (FMO) is active towards many drugs with
      a heteroatom having the properties of a soft nucleophile. Thiocarbamides and
      thiones are S-oxygenated to the sulfenic acid which can either react with
      glutathione and initiate a redox-cycle or be oxygenated a second time to the
      unstable sulfinic acid. In this study, we utilized LC-MS/MS to demonstrate that
      the oxygenation by hFMO of the thioureas under test terminated at the sulfenic
      acid. With thiones, hFMO catalyzed the second reaction and the sulfinic acid
      rapidly lost sulfite to form the corresponding imidazole. Thioureas are often
      pulmonary toxicants in mammals and, as previously reported by our laboratory, are
      excellent substrates for hFMO2. This isoform is expressed at high levels in the
      lung of most mammals, including non-human primates. Genotyping to date indicates
      that individuals of African (up to 49%) or Hispanic (2-7%) ancestry have at least
      one allele for functional hFMO2 in lung, but not Caucasians nor Asians. In this
      study the major metabolite formed by hFMO2 with thioureas from Allergan, Inc. was
      the sulfenic acid that reacted with glutathione. The majority of thiones were
      poor substrates for hFMO3, the major form in adult human liver. However, hFMO1,
      the major isoform expressed in infant and neonatal liver and adult kidney and
      intestine, readily S-oxygenated thiones under test, with Kms ranging from 7 to
      160 MUM and turnover numbers of 30-40 min(-1). The product formed was identified
      by LC-MS/MS as the imidazole. The activities of the mouse and human FMO1 and FMO3
      orthologs were in good agreement with the exception of some thiones for which
      activity was much greater with hFMO1 than mFMO1.

PMID- 24727369
TI  - Exploring the "active ingredients" of an online smoking intervention: a
      randomized factorial trial.
AB  - INTRODUCTION: Research needs to systematically identify which components increase
      online intervention effectiveness (i.e., active ingredients). This study explores
      the effects of 4 potentially important design features in an Internet-based,
      population-level smoking intervention. METHODS: Smokers (n = 1,865) were
      recruited from a large health care organization, regardless of readiness to quit.
      Using a full factorial design, participants were randomized to 1 of the 2 levels
      of each experimental factor (message tone [prescriptive vs. motivational],
      navigation autonomy [dictated vs. not], e-mail reminders [yes vs. no], and
      receipt of personally tailored testimonials [yes vs. no]) and provided access to
      the online intervention. Primary outcomes were self-reported 7-day point
      prevalent smoking abstinence and confirmed utilization of adjunct treatment
      (pharmacotherapy or phone counseling) available through the health plan at 1
      year. Outcomes were also assessed at 2 and 6 months and were examined among all
      enrolled participants (intent-to-treat [ITT]) and all who viewed the intervention
      (modified ITT). RESULTS: At 1 year, 13.7% were abstinent and 26.0% utilized
      adjunct treatment. None of the contrasting factor levels differentially
      influenced abstinence or treatment utilization at 12 months. In the modified ITT
      sample, smokers receiving testimonials were less likely to use adjunct treatment
      at 6 months (odds ratio = 0.54, 95% confidence interval = 0.30-0.98, p = .04).
      CONCLUSIONS: None of the design features enhanced treatment outcome. The negative
      effect observed for testimonials is provocative, but it should be viewed with
      caution. This study offers a model for future research testing the "active
      ingredients" of online interventions.

PMID- 24727370
TI  - A longitudinal study of the correlates of persistent smoking among sexual
      minority women.
AB  - INTRODUCTION: We conducted a longitudinal evaluation of factors associated with
      persistent smoking behaviors among sexual minority women (SMW; lesbians and
      bisexual women). METHODS: Structured interview data were collected as part of a
      larger longitudinal study of SMW's health: the Chicago Health and Life
      Experiences of Women study. We conducted multivariate analyses to evaluate the
      influence of 4 groups of predictor variables on smoking: (a) demographic, (b)
      childhood victimization, (c) other substance use, and (d) health variables.
      RESULTS: At Wave 1, 30.9% (n = 138) of participants reported current smoking,
      with substance-use and demographic factors having the strongest relationships to
      smoking status. The majority (84.9%) of Wave 1 smokers were also smoking at Wave
      2. Among demographic variables, level of education was inversely associated with
      continued smoking. With respect to substance use, hazardous drinking and
      cocaine/heroin use were significantly associated with continued smoking. None of
      the victimization or health variables predicted smoking status. CONCLUSIONS:
      Consistent with previous studies, smoking rates in this sample of SMW were
      elevated. Despite intensive efforts to reduce smoking in the general population,
      84% of SMW smokers continued smoking from Wave 1 to Wave 2. Findings suggest that
      the majority of SMW will continue to smoke over time. Additional research is
      needed to increase motivation and access to smoking cessation resources.

PMID- 24727371
TI  - Coupling between acto-adhesive machinery and ECM degradation in invadosomes.
AB  - Invadosomes have two main functions represented by their actin-rich and adhesive
      components and their polarized secretory pathways controlling the delivery of
      metalloproteases necessary to degrade extracellular matrix (ECM). Invadosomes
      include invadopodia and podosomes, which have subtle differences in molecular
      composition, dynamics, and structure. These differences could reflect different
      stages of invadosome maturation. This review will outline current knowledge on
      the coupling between the acto-adhesive machinery and the ECM degradation activity
      in invadosome diversity. Multiple works support that these two functions are not
      automatically linked but seem to be finely regulated to allow different functions
      of invadosomes. We will explore the paradigmatic aspect of invadosomes, which are
      able to interact with ECM to degrade it so as to better control their own
      dynamics. Understanding the fine-tuning between these two functions could serve
      to understand the link between the different types of invadosomes from
      invadopodia to podosomes. 

PMID- 24727372
TI  - The activity of nodules of the supernodulating mutant Mtsunn is not limited by
      photosynthesis under optimal growth conditions.
AB  - Legumes match the nodule number to the N demand of the plant. When a mutation in
      the regulatory mechanism deprives the plant of that ability, an excessive number
      of nodules are formed. These mutants show low productivity in the fields, mainly
      due to the high carbon burden caused through the necessity to supply numerous
      nodules. The objective of this study was to clarify whether through optimal
      conditions for growth and CO2 assimilation a higher nodule activity of a
      supernodulating mutant of Medicago truncatula (M. truncatula) can be induced.
      Several experimental approaches reveal that under the conditions of our
      experiments, the nitrogen fixation of the supernodulating mutant, designated as
      sunn (super numeric nodules), was not limited by photosynthesis. Higher specific
      nitrogen fixation activity could not be induced through short- or long-term
      increases in CO2 assimilation around shoots. Furthermore, a whole plant P
      depletion induced a decline in nitrogen fixation, however this decline did not
      occur significantly earlier in sunn plants, nor was it more intense compared to
      the wild-type. However, a distinctly different pattern of nitrogen fixation
      during the day/night cycles of the experiment indicates that the control of N2
      fixing activity of the large number of nodules is an additional problem for the
      productivity of supernodulating mutants. 

PMID- 24727374
TI  - Asymmetric dimethylarginine in chronic obstructive pulmonary disease (ADMA in
      COPD).
AB  - L-arginine metabolism including the nitric oxide (NO) synthase and arginase
      pathways is important in the maintenance of airways function. We have previously
      reported that accumulation of asymmetric dimethylarginine (ADMA) in airways,
      resulting in changes in L-arginine metabolism, contributes to airways obstruction
      in asthma and cystic fibrosis. Herein, we assessed L-arginine metabolism in
      airways of patients with chronic obstructive pulmonary disease (COPD). Lung
      function testing, measurement of fractional exhaled NO (FeNO) and sputum NO
      metabolites, as well as quantification of L-arginine metabolites (L-arginine, L
      ornithine, L-citrulline, ADMA and symmetric dimethylarginine) using liquid
      chromatography-mass spectrometry (LC-MS) were performed. Concentrations of L
      ornithine, the product of arginase activity, correlated directly with L-arginine
      and ADMA sputum concentrations. FeNO correlated directly with pre- and post
      bronchodilator forced expiratory volume in one second (FEV1). Sputum arginase
      activity correlated inversely with total NO metabolite (NOx) and nitrite
      concentrations in sputum, and with pre- and post-bronchodilator FEV1. These
      findings suggest that ADMA in COPD airways results in a functionally relevant
      shift of L-arginine breakdown by the NO synthases towards the arginase pathway,
      which contributes to airway obstruction in these patients.

PMID- 24727373
TI  - PSMA, EpCAM, VEGF and GRPR as imaging targets in locally recurrent prostate
      cancer after radiotherapy.
AB  - In this retrospective pilot study, the expression of the prostate-specific
      membrane antigen (PSMA), the epithelial cell adhesion molecule (EpCAM), the
      vascular endothelial growth factor (VEGF) and the gastrin-releasing peptide
      receptor (GRPR) in locally recurrent prostate cancer after brachytherapy or
      external beam radiotherapy (EBRT) was investigated, and their adequacy for
      targeted imaging was analyzed. Prostate cancer specimens were collected of 17
      patients who underwent salvage prostatectomy because of locally recurrent
      prostate cancer after brachytherapy or EBRT. Immunohistochemistry was performed.
      A pathologist scored the immunoreactivity in prostate cancer and stroma. Staining
      for PSMA was seen in 100% (17/17), EpCAM in 82.3% (14/17), VEGF in 82.3% (14/17)
      and GRPR in 100% (17/17) of prostate cancer specimens. Staining for PSMA, EpCAM
      and VEGF was seen in 0% (0/17) and for GRPR in 100% (17/17) of the specimens'
      stromal compartments. In 11.8% (2/17) of cases, the GRPR staining intensity of
      prostate cancer was higher than stroma, while in 88.2% (15/17), the staining was
      equal. Based on the absence of stromal staining, PSMA, EpCAM and VEGF show high
      tumor distinctiveness. Therefore, PSMA, EpCAM and VEGF can be used as targets for
      the bioimaging of recurrent prostate cancer after EBRT to exclude metastatic
      disease and/or to plan local salvage therapy. 

PMID- 24727375
TI  - Comparative pulmonary toxicity of two ceria nanoparticles with the same primary
      size.
AB  - Ceria nanoparticles (nano-ceria) have recently gained a wide range of
      applications, which might pose unwanted risks to both the environment and human
      health. The greatest potential for the environmental discharge of nano-ceria
      appears to be in their use as a diesel fuel additive. The present study was
      designed to explore the pulmonary toxicity of nano-ceria in mice after a single
      exposure via intratracheal instillation. Two types of nano-ceria with the same
      distribution of a primary size (3-5 nm), but different redox activity, were used:
      Ceria-p, synthesized by a precipitation route, and Ceria-h, synthesized by a
      hydrothermal route. Both Ceria-p and Ceria-h induced oxidative stress,
      inflammatory responses and cytotoxicity in mice, but their toxicological profiles
      were quite different. The mean size of Ceria-p agglomerates was much smaller
      compared to Ceria-h, thereby causing a more potent acute inflammation, due to
      their higher number concentration of agglomerates and higher deposition rate in
      the deep lung. Ceria-h had a higher reactivity to catalyzing the generation of
      reactive oxygen species (ROS), and caused two waves of lung injury:
      bronchoalveolar lavage (BAL) inflammation and cytotoxicity in the early stage and
      redox-activity-evoked lipid peroxidation and pro-inflammation in the latter
      stage. Therefore, the size distribution of ceria-containing agglomerates in the
      exhaust, as well as their surface chemistry are essential characteristics to
      assess the potential risks of using nano-ceria as a fuel additive. 

PMID- 24727376
TI  - DNA comet Giemsa staining for conventional bright-field microscopy.
AB  - This study was undertaken to evaluate the compatibility of Giemsa staining
      protocol with the comet assay. We showed, for the first time, that DNA comets can
      be visualized and analyzed using Giemsa staining. We generated DNA damage dose
      response curves for human peripheral blood lymphocytes exposed to X-ray radiation
      using the comet assay with either SybrGreen I or Giemsa stain. The dose response
      curves were fitted by linear regressions (R2>0.977). The SybrGreen I results
      showed only ~1.2-fold higher slope coefficient (method sensitivity) compared to
      the Giemsa results. The unexpectedly high sensitivity of Giemsa staining for the
      comet assay is due to the Romanowsky-Giemsa effect, the stain photo-stability and
      the higher resolution of bright-field imaging compared to fluorescence imaging.
      Our results demonstrate that Giemsa staining can effectively be used for
      measuring DNA damage by the comet assay. The low cost and availability of Giemsa
      stain makes this method affordable for any low budget research and will
      facilitate new applications of the comet assay in biology and medicine.

PMID- 24727377
TI  - Human adipose-derived mesenchymal stem cells are resistant to HBV infection
      during differentiation into hepatocytes in vitro.
AB  - The therapeutic methods for chronic hepatitis B are limited. The shortage of
      organ donors and hepatitis B virus (HBV) reinfection obstruct the clinical
      application of orthotopic liver transplantation (OLT). In the present study,
      adipose-derived mesenchymal stem cells (AD-MSCs) and bone marrow-derived
      mesenchymal stem cells (BM-MSCs) were isolated from chronic hepatitis B patients
      and characterized for morphology, growth potency, surface phenotype and the
      differentiation potential. The results showed that both MSCs had adipogenic,
      osteogenic and neuron differentiation potential, and nearly all MSCs expressed
      CD105, CD44 and CD29. Compared with AD-MSCs, BM-MSCs of chronic hepatitis B
      patients proliferated defectively. In addition, the ability of AD-MSCs to
      differentiate into hepatocyte was evaluated and the susceptibility to HBV
      infection were assessed. AD-MSCs could differentiate into functional hepatocyte
      like cells. These cells express the hepatic-specific markers and have glycogen
      production and albumin secretion function. AD-MSCs and hepatic differentiation AD
      MSCs were not susceptible to infection by HBV in vitro. Compared with BM-MSCs, AD
      MSCs may be alternative stem cells for chronic hepatitis B patients. 

PMID- 24727378
TI  - Molecular imprinted polymer of methacrylic acid functionalised beta-cyclodextrin
      for selective removal of 2,4-dichlorophenol.
AB  - This work describes methacrylic acid functionalized beta-cyclodextrin (MAA
      betaCD) as a novel functional monomer in the preparation of molecular imprinted
      polymer (MIP MAA-betaCD) for the selective removal of 2,4-dichlorophenol (2,4
      DCP). The polymer was characterized using Fourier Transform Infrared (FTIR)
      spectroscopy, Brunauer-Emmett-Teller (BET) and Field Emission Scanning Electron
      Microscopy (FESEM) techniques. The influence of parameters such as solution pH,
      contact time, temperature and initial concentrations towards removal of 2,4-DCP
      using MIP MAA-betaCD have been evaluated. The imprinted material shows fast
      kinetics and the optimum pH for removal of 2,4-DCP is pH 7. Compared with the
      corresponding non-imprinted polymer (NIP MAA-betaCD), the MIP MAA-betaCD
      exhibited higher adsorption capacity and outstanding selectivity towards 2,4-DCP.
      Freundlich isotherm best fitted the adsorption equilibrium data of MIP MAA-betaCD
      and the kinetics followed a pseudo-second-order model. The calculated
      thermodynamic parameters showed that adsorption of 2,4-DCP was spontaneous and
      exothermic under the examined conditions. 

PMID- 24727379
TI  - Crystal structure of HIV-1 Tat complexed with human P-TEFb and AFF4.
AB  - Developing anti-viral therapies targeting HIV-1 transcription has been hampered
      by the limited structural knowledge of the proteins involved. HIV-1 hijacks the
      cellular machinery that controls RNA polymerase II elongation through an
      interaction of HIV-1 Tat with the positive transcription elongation factor P
      TEFb, which interacts with an AF4 family member (AFF1/2/3/4) in the super
      elongation complex (SEC). Because inclusion of Tat*P-TEFb into the SEC is
      critical for HIV transcription, we have determined the crystal structure of the
      Tat*AFF4*P-TEFb complex containing HIV-1 Tat (residues 1-48), human Cyclin T1 (1
      266), human Cdk9 (7-332), and human AFF4 (27-69). Tat binding to AFF4*P-TEFb
      causes concerted structural changes in AFF4 via a shift of helix H5' of Cyclin T1
      and the alpha-3 10 helix of AFF4. The interaction between Tat and AFF4 provides
      structural constraints that explain tolerated Tat mutations. Analysis of the Tat
      binding surface of AFF4 coupled with modeling of all other AF4 family members
      suggests that AFF1 and AFF4 would be preferred over AFF2 or AFF3 for interaction
      with Tat*P-TEFb. The structure establishes that the Tat-TAR recognition motif
      (TRM) in Cyclin T1 interacts with both Tat and AFF4, leading to the exposure of
      arginine side chains for binding to TAR RNA. Furthermore, modeling of Tat Lys28
      acetylation suggests that the acetyl group would be in a favorable position for H
      bond formation with Asn257 of TRM, thereby stabilizing the TRM in Cyclin T1, and
      provides a structural basis for the modulation of TAR RNA binding by acetylation
      of Tat Lys28. 

PMID- 24727380
TI  - Developing a new assessment procedure of social information processing in
      adolescents within secure residential care.
AB  - The purpose of the present study was to develop a new assessment procedure of
      social information processing (SIP) for adolescents, to explore its validity and
      to examine whether it differentiated between IQ groups. Ninety-four adolescents
      within secure residential care were administered the SIP instrument, the Youth
      Self Report and two subtests of the WISC/WAIS. Results showed that the constructs
      underlying the items of the instrument were associated with profiles from the SIP
      theory, the subsequent SIP steps were correlated, and several SIP steps were
      correlated to self-reported behavior. No differences were found between IQ
      groups. These first results have implications for adjustment of the instrument.
      Further research should confirm construct validity and psychometric qualities of
      the scales. 

PMID- 24727381
TI  - The prevalence and impact of Fusarium head blight pathogens and mycotoxins on
      malting barley quality in UK.
AB  - Fusarium head blight (FHB) caused by Fusarium and Microdochium species can
      significantly affect the yield of barley grain as well as the quality and safety
      of malt and beer. The present study provides new knowledge on the impacts of the
      FHB pathogen complex on the malting and brewing quality parameters of naturally
      infected barley. Quantitative real-time PCR and liquid chromatography double mass
      spectrometry were used to quantify the predominant FHB pathogens and Fusarium
      mycotoxins, respectively, in commercially grown UK malting barley samples
      collected between 2007 and 2011. The predominant Fusarium species identified
      across the years were F. poae, F. tricinctum and F. avenaceum. Microdochium majus
      was the predominant Microdochium species in 2007, 2008, 2010 and 2011 whilst
      Microdochium nivale predominated in 2009. Deoxynivalenol and zearalenone
      quantified in samples collected between 2007 and 2009 were associated with F.
      graminearum and F. culmorum, whilst HT-2 and T-2, and nivalenol in samples
      collected between 2010 and 2011 correlated positively with F. langsethiae and F.
      poae, respectively. Analysis of the regional distribution and yearly variation in
      samples from 2010 to 2011 showed significant differences in the composition of
      the FHB species complex. In most regions (Scotland, the South and North of
      England) the harvest in 2010 had higher concentrations of Fusarium spp. than in
      2011, although no significant difference was observed in the Midlands between the
      two years. Microdochium DNA was significantly higher in 2011 and in the North of
      England and Scotland compared to the South or Midlands regions. Pathogens of the
      FHB complex impacted negatively on grain yield and quality parameters. Thousand
      grain weight of malting barley was affected significantly by M. nivale and M.
      majus whilst specific weight correlated negatively with F. avenaceum and F.
      graminearum. To determine the impact of sub-acute infections of the identified
      Fusarium and Microdochium species on malting and brewing quality of naturally
      infected samples, selected malting barley cultivars (Optic, Quench and Tipple)
      were micromalted and subjected to malt and wort analysis of key quality
      parameters. F. poae and M. nivale decreased germinative energy and increased
      water sensitivity of barley. The fungal biomass of F. poae and F. langsethiae
      correlated with increased wort free amino nitrogen and with decreased extract of
      malt. DNA of M. nivale correlated with increased malt friability as well as
      decreased wort filtration volume. The findings of this study indicate that the
      impact of species such as the newly emerging F. langsethiae, as well as F. poae
      and the two non-toxigenic Microdochium species should be considered when
      evaluating the quality of malting barley. 

PMID- 24727382
TI  - Fate of Vibrio parahaemolyticus on shrimp after acidic electrolyzed water
      treatment.
AB  - The objective of this study was to investigate the fate of Vibrio
      parahaemolyticus on shrimp after acidic electrolyzed water (AEW) treatment during
      storage. Shrimp, inoculated with a cocktail of four strains of V.
      parahaemolyticus, were stored at different temperatures (4-30  degrees C) after
      AEW treatment. Experimental data were fitted to modified Gompertz and Log-linear
      models. The fate of V. parahaemolyticus was determined based on the growth and
      survival kinetics parameters (lag time, lambda; the maximum growth rate, MUmax;
      the maximum growth concentration, D; the inactivation value, K) depending on the
      respective storage conditions. Moreover, real-time PCR was employed to study the
      population dynamics of this pathogen during the refrigeration temperature storage
      (10, 7, 4  degrees C). The results showed that AEW treatment could markedly
      (p<0.05) decrease the growth rate (MUmax) and extend the lag time (lambda) during
      the post-treatment storage at 30, 25, 20 and 15  degrees C, while it did not
      present a capability to lower the maximum growth concentration (D). AEW treatment
      increased the sensitivity of V. parahaemolyticus to refrigeration temperatures,
      indicated by a higher (p<0.05) inactivation value (K) of V. parahaemolyticus,
      especially for 10  degrees C storage. The results also revealed that AEW
      treatment could completely suppress the proliferation of V. parahaemolyticus in
      combination with refrigeration temperature. Based on above analysis, the present
      study demonstrates the potential of AEW in growth inhibition or death
      acceleration of V. parahaemolyticus on seafood, hence to greatly reduce the risk
      of illness caused by this pathogen during post-treatment storage.

PMID- 24727383
TI  - Trichothecene genotypes and production profiles of Fusarium graminearum isolates
      obtained from barley cultivated in Argentina.
AB  - Fusarium graminearum is one of the most important pathogens isolated from small
      cereal grains with Fusarium Head Blight symptoms. The presence of this fungus is
      often linked to the occurrence of several mycotoxins in barley and wheat. The aim
      of our study was to characterize trichothecene genotypes and production profiles
      of F. graminearum sensu stricto isolates obtained from barley grains in
      Argentina. A total of 110 F. graminearum s.s. isolates were analyzed by PCR
      assays to predict deoxynivalenol (DON), 15-acetyldeoxynivalenol (15-ADON), 3
      acetyldeoxynivalenol (3-ADON) and nivalenol (NIV) production, and all isolates
      were found to belong to the same molecular 15-ADON genotype. Trichothecene
      production in autoclaved rice was analyzed by using gas chromatography (GC) and
      confirmed by GC-MS. Of the 110 isolates, 95% were able to produce DON, 71%
      produced 15-ADON, 63% 3-ADON and 52% NIV. With the exception of a single isolate,
      all isolates that produced NIV, also produced DON. However, the NIV production
      was very low, ranging from 0.13 to 0.30 MUg/g. Six different production profiles
      of DON and its acetyl-derivatives were detected, the predominant being
      simultaneous production of DON, 3-ADON and 15-ADON, followed by DON production,
      and DON and 15-ADON co-production. This work is the first attempt to characterize
      the trichothecene genotypes and production profiles of F. graminearum s.s.
      isolates from Argentinean barley.

PMID- 24727384
TI  - Prostate-specific antigen and other serum and urine markers in prostate cancer.
AB  - Prostate-specific antigen (PSA) is one of the most widely used tumor markers, and
      strongly correlates with the risk of harboring from prostate cancer (PCa). This
      risk is visible already several years in advance but PSA has severe limitations
      for PCa detection with its low specificity and low negative predictive value.
      There is an urgent need for new biomarkers especially to detect clinically
      significant and aggressive PCa. From all PSA-based markers, the FDA-approved
      Prostate Health Index (phi) shows improved specificity over percent free and
      total PSA. Other serum kallikreins or sarcosine in serum or urine show more
      diverging data. In urine, the FDA-approved prostate cancer gene 3 (PCA3) has also
      proven its utility in the detection and management of early PCa. However, some
      aspects on its correlation with aggressiveness and the low sensitivity at very
      high values have to be re-examined. The detection of a fusion of the androgen
      regulated TMPRSS2 gene with the ERG oncogene (from the ETS family), which acts as
      transcription factor gene, in tissue of ~50% of all PCa patients was one
      milestone in PCa research. When combining the urinary assays for TMPRSS2:ERG and
      PCA3, an improved accuracy for PCa detection is visible. PCA3 and phi as the best
      available PCa biomarkers show an equal performance in direct comparisons. 

PMID- 24727386
TI  - Opportunities for translation: targeting DNA repair pathways in pancreatic
      cancer.
AB  - Pancreatic ductal adenocarcinoma (PDAC) remains one of the poorest prognosis
      neoplasms. It is typified by high levels of genomic aberrations and copy-number
      variation, intra-tumoural heterogeneity and resistance to conventional
      chemotherapy. Improved therapeutic options, ideally targeted against cancer
      specific biological mechanisms, are urgently needed. Although induction of DNA
      damage and/or modulation of DNA damage response pathways are associated with the
      activity of a number of conventional PDAC chemotherapies, the effectiveness of
      this approach in the treatment of PDAC has not been comprehensively reviewed.
      Here, we review chemotherapeutic agents that have shown anti-cancer activity in
      PDAC and whose mechanisms of action involve modulation of DNA repair pathways. In
      addition, we highlight novel potential targets within these pathways based on the
      emerging understanding of PDAC biology and their exploitation as targets in other
      cancers. 

PMID- 24727388
TI  - ESCMID postgraduate technical workshop on intracellular bacteria: from biology to
      clinic.
AB  - Infection by intracellular bacteria can lead to several diseases in both
      veterinary and human medicine. Unfortunately, the biology of these intracellular
      bacteria is highly complex due to their interactions with their host cells. Thus,
      it is very important to develop several tools in order to better understand the
      complex intracellular life of these pathogens, so allowing to improve the
      diagnosis options and the treatments of infectious diseases that they are
      causing. The workshop organised in Villars-sur-Ollon (Switzerland) by the ESCMID
      Study group on intracellular bacteria was a good opportunity to enhance our
      knowledge on these fastidious pathogens. During 5 days, 15 speakers gave 41
      talks, covering all fields, from biology to clinic of different intracellular
      bacteria such as Bartonella, Chlamydia, Coxiella, Ehrlichia, Listeria,
      Parachlamydia, Rickettsia, and Waddlia. The format of this postgraduate course,
      which took place in the Swiss mountains, allowed interactive sessions and living
      discussions between the participants coming from all around the world. One of the
      major strength was to gather epidemiologists, clinical microbiologists,
      infectious diseases specialists, entomologists, veterinarians as well as
      bioinformaticians, biochemists and biologists to deliver a unique "one-health
      science" on intracellular bacteria. Here, we summarise the main take-home
      messages delivered during this meeting.

PMID- 24727389
TI  - Real-time 3D radiation risk assessment supporting simulation of work in nuclear
      environments.
AB  - This paper describes the latest developments at the Institute for Energy
      Technology (IFE) in Norway, in the field of real-time 3D (three-dimensional)
      radiation risk assessment for the support of work simulation in nuclear
      environments. 3D computer simulation can greatly facilitate efficient work
      planning, briefing, and training of workers. It can also support communication
      within and between work teams, and with advisors, regulators, the media and
      public, at all the stages of a nuclear installation's lifecycle. Furthermore, it
      is also a beneficial tool for reviewing current work practices in order to
      identify possible gaps in procedures, as well as to support the updating of
      international recommendations, dissemination of experience, and education of the
      current and future generation of workers.IFE has been involved in research and
      development into the application of 3D computer simulation and virtual reality
      (VR) technology to support work in radiological environments in the nuclear
      sector since the mid 1990s. During this process, two significant software tools
      have been developed, the VRdose system and the Halden Planner, and a number of
      publications have been produced to contribute to improving the safety culture in
      the nuclear industry.This paper describes the radiation risk assessment
      techniques applied in earlier versions of the VRdose system and the Halden
      Planner, for visualising radiation fields and calculating dose, and presents new
      developments towards implementing a flexible and up-to-date dosimetric package in
      these 3D software tools, based on new developments in the field of radiation
      protection. The latest versions of these 3D tools are capable of more accurate
      risk estimation, permit more flexibility via a range of user choices, and are
      applicable to a wider range of irradiation situations than their predecessors. 

PMID- 24727385
TI  - Signaling pathways involved in MDSC regulation.
AB  - The immune system has evolved mechanisms to protect the host from the deleterious
      effects of inflammation. The generation of immune suppressive cells like myeloid
      derived suppressor cells (MDSCs) that can counteract T cell responses represents
      one such strategy. There is an accumulation of immature myeloid cells or MDSCs in
      bone marrow (BM) and lymphoid organs under pathological conditions such as
      cancer. MDSCs represent a population of heterogeneous myeloid cells comprising of
      macrophages, granulocytes and dendritic cells that are at early stages of
      development. Although, the precise signaling pathways and molecular mechanisms
      that lead to MDSC generation and expansion in cancer remains to be elucidated. It
      is widely believed that perturbation of signaling pathways involved during normal
      hematopoietic and myeloid development under pathological conditions such as
      tumorogenesis contributes to the development of suppressive myeloid cells. In
      this review we discuss the role played by key signaling pathways such as PI3K,
      Ras, Jak/Stat and TGFb during myeloid development and how their deregulation
      under pathological conditions can lead to the generation of suppressive myeloid
      cells or MDSCs. Targeting these pathways should help in elucidating mechanisms
      that lead to the expansion of MDSCs in cancer and point to methods for
      eliminating these cells from the tumor microenvironment. 

PMID- 24727390
TI  - Briarane diterpenoids isolated from gorgonian corals between 2011 and 2013.
AB  - The structures, names, bioactivities and references of 138 briarane-type
      diterpenoids, including 87 new compounds, are summarized in this review. All the
      briarane-type compounds mentioned in this review article were obtained from
      gorgonian corals including the genus Briareum, Dichotella, Junceella and
      Verrucella. Some of these compounds showed potential bioactivities. 

PMID- 24727391
TI  - Pelagia noctiluca (Scyphozoa) crude venom injection elicits oxidative stress and
      inflammatory response in rats.
AB  - Cnidarian toxins represent a rich source of biologically active compounds. Since
      they may act via oxidative stress events, the aim of the present study was to
      verify whether crude venom, extracted from the jellyfish Pelagia noctiluca,
      elicits inflammation and oxidative stress processes, known to be mediated by
      Reactive Oxygen Species (ROS) production, in rats. In a first set of experiments,
      the animals were injected with crude venom (at three different doses 6, 30 and 60
      ug/kg, suspended in saline solution, i.v.) to test the mortality and possible
      blood pressure changes. In a second set of experiments, to confirm that Pelagia
      noctiluca crude venom enhances ROS formation and may contribute to the
      pathophysiology of inflammation, crude venom-injected animals (30 ug/kg) were
      also treated with tempol, a powerful antioxidant (100 mg/kg i.p., 30 and 60 min
      after crude venom). Administration of tempol after crude venom challenge, caused
      a significant reduction of each parameter related to inflammation. The potential
      effect of Pelagia noctiluca crude venom in the systemic inflammation process has
      been here demonstrated, adding novel information about its biological activity. 

PMID- 24727392
TI  - Simple and rapid quality control of sulfated glycans by a fluorescence sensor
      assay--exemplarily developed for the sulfated polysaccharides from red algae
      Delesseria sanguinea.
AB  - Sulfated polysaccharides (SP) from algae are of great interest due to their
      manifold biological activities. Obstacles to commercial (especially medical)
      application include considerable variability and complex chemical composition
      making the analysis and the quality control challenging. The aim of this study
      was to evaluate a simple microplate assay for screening the quality of SP. It is
      based on the fluorescence intensity (FI) increase of the sensor molecule Polymer
      H by SP and was originally developed for direct quantification of SP.
      Exemplarily, 65 SP batches isolated from the red alga Delesseria sanguinea (D.s.
      SP) and several other algae polysaccharides were investigated. Their FI increase
      in the Polymer-H assay was compared with other analytical parameters. By testing
      just one concentration of a D.s.-SP sample, quality deviations from the reference
      D.s.-SP and thus both batch-to-batch variability and stability can be detected.
      Further, structurally distinct SP showed to differ in their concentration
      dependent FI profiles. By using corresponding reference compounds, the Polymer-H
      assay is therefore applicable as identification assay with high negative
      predictability. In conclusion, the Polymer-H assay showed to represent not only a
      simple method for quantification, but also for characterization identification
      and differentiation of SP of marine origin. 

PMID- 24727393
TI  - Maritime halophyte species from southern Portugal as sources of bioactive
      molecules.
AB  - Extracts of five halophytes from southern Portugal (Arthrocnemum macrostachyum,
      Mesembryanthemum edule, Juncus acutus, Plantago coronopus and Halimione
      portulacoides), were studied for antioxidant, anti-inflammatory and in vitro
      antitumor properties. The most active extracts towards the 1,1-diphenyl-2
      picrylhydrazyl (DPPH) radical were the methanol extracts of M. edule (IC50 = 0.1
      mg/mL) and J. acutus (IC50 = 0.4 mg/mL), and the ether extracts of J. acutus
      (IC50 = 0.2 mg/mL) and A. macrostachyum (IC50 = 0.3 mg/mL). The highest radical
      scavenging activity (RSA) against the 2,2'-azino-bis (3-ethylbenzothiazoline-6
      sulphonic acid) (ABTS) radical was obtained in the ether extract of J. acutus
      (IC50 = 0.4 mg/mL) and H. portulacoides (IC50 = 0.9 mg/mL). The maximum total
      phenolic content (TPC) was found in the methanol extract of M. edule (147 mg
      gallic acid equivalents (GAE)/g) and in the ether extract of J. acutus (94 mg
      GAE/g). Significant decreases in nitric oxide (NO) production were observed after
      incubation of macrophages with lipopolysaccharide (LPS) and the chloroform
      extract of H. portulacoides (IC50 = 109 ug/mL) and the hexane extract of P.
      coronopus (IC50 = 98.0 ug/mL). High in vitro cytotoxic activity and selectivity
      was obtained with the ether extract of J. acutus. Juncunol was identified as the
      active compound and for the first time was shown to display selective in vitro
      cytotoxicity towards various human cancer cells.

PMID- 24727394
TI  - Modification of chitin with kraft lignin and development of new biosorbents for
      removal of cadmium(II) and nickel(II) ions.
AB  - Novel, functional materials based on chitin of marine origin and lignin were
      prepared. The synthesized materials were subjected to physicochemical, dispersive
      morphological and electrokinetic analysis. The results confirm the effectiveness
      of the proposed method of synthesis of functional chitin/lignin materials.
      Mechanism of chitin modification by lignin is based on formation of hydrogen
      bonds between chitin and lignin. Additionally, the chitin/lignin materials were
      studied from the perspective of waste water treatment. The synthetic method
      presented in this work shows an attractive and facile route for producing low
      cost chitin/lignin biosorbents with high efficiency of nickel and cadmium
      adsorption (88.0% and 98.4%, respectively). The discovery of this facile method
      of synthesis of functional chitin/lignin materials will also have a significant
      impact on the problematic issue of the utilization of chitinous waste from the
      seafood industry, as well as lignin by-products from the pulp and paper industry.

PMID- 24727395
TI  - Effects of chitin and sepia ink hybrid hemostatic sponge on the blood parameters
      of mice.
AB  - Chitin and sepia ink hybrid hemostatic sponge (CTSH sponge), a new biomedical
      material, was extensively studied for its beneficial biological properties of
      hemostasis and stimulation of healing. However, studies examining the safety of
      CTSH sponge in the blood system are lacking. This experiment aimed to examine
      whether CTSH sponge has negative effect on blood systems of mice, which were
      treated with a dosage of CTSH sponge (135 mg/kg) through a laparotomy. CTSH
      sponge was implanted into the abdominal subcutaneous and a laparotomy was used
      for blood sampling from abdominal aortic. Several kinds of blood parameters were
      detected at different time points, which were reflected by coagulation parameters
      including thrombin time (TT), prothrombin time (PT), activated partial
      thromboplatin time (APTT), fibrinogen (FIB) and platelet factor 4 (PF4);
      anticoagulation parameter including antithrombin III (AT-III); fibrinolytic
      parameters including plasminogen (PLG), fibrin degradation product (FDP) and D
      dimer; hemorheology parameters including blood viscosity (BV) and plasma
      viscosity (PV). Results showed that CTSH sponge has no significant effect on the
      blood parameters of mice. The data suggested that CTSH sponge can be applied in
      the field of biomedical materials and has potential possibility to be developed
      into clinical drugs of hemostatic agents. 

PMID- 24727396
TI  - Sex differences in theory-based predictors of leisure time physical activity in a
      population-based sample of adults with spinal cord injury.
AB  - OBJECTIVE: To examine sex differences in theory-based predictors of leisure time
      physical activity (LTPA) among men and women with spinal cord injury, and
      secondarily, to identify factors that might explain any sex differences in social
      cognitions. DESIGN: A secondary analysis of Study of Health and Activity in
      People with Spinal Cord Injury survey data. SETTING: Community. PARTICIPANTS:
      Community-dwelling men (n=536) and women (n=164) recruited from 4 rehabilitation
      and research centers. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES:
      Subjective norms, attitudes, barrier self-efficacy, perceived controllability
      (PC), and intentions. RESULTS: Men had stronger PC and barrier self-efficacy than
      women. Hierarchical regression analyses revealed that social support
      significantly predicted PC for both sexes, and health, pain, and physical
      independence also significantly predicted PC for men. Social support, health, and
      pain significantly predicted barrier self-efficacy for men. Social support was
      the only significant predictor of barrier self-efficacy for women. CONCLUSIONS:
      Women felt significantly less control over their physical activity behavior and
      had lower confidence to overcome barriers to physical activity than did men.
      Although social support predicted PC and barrier self-efficacy in both men and
      women, men seemed to take additional factors into consideration when formulating
      their control beliefs for LTPA.

PMID- 24727397
TI  - Outcome of endovascular treatment in postthrombotic syndrome.
AB  - BACKGROUND: The postthrombotic syndrome (PTS) is a chronic complication of deep
      venous thrombosis (DVT) that is characterized by leg swelling and ulceration.
      METHODS: Sixty-seven cases of PTS underwent attempted endovascular treatment with
      success in 63 between June 2005 and June 2012. Thirty-six cases underwent
      endovascular treatment only and 18 cases combined with temporary femoral
      arteriovenous fistula, 5 cases great saphenous vein ligation and stripping
      whereas 4 cases with communicating branch ligation around ulcers. RESULTS:
      Stenting was successfully performed in 63 of 67 patients. The technical success
      rate was 94% with no mortality. Fifty-eight cases were followed up from 1 to 84
      months. Stent occlusion or restenosis occurred in 17 patients. The primary and
      secondary patency rates were 87.9% and 93.1%, respectively, at 12 months and
      70.7% and 82.8%, respectively, at 36 months. CONCLUSIONS: Endovascular treatment
      of PTS is safe and effective. It can alleviate symptoms and prevent further
      deterioration of patients with PTS.

PMID- 24727398
TI  - Determining the life cycle energy efficiency of six biofuel systems in China: a
      Data Envelopment Analysis.
AB  - This aim of this study was to use Data Envelopment Analysis (DEA) to assess the
      life cycle energy efficiency of six biofuels in China. DEA can differentiate
      efficient and non-efficient scenarios, and it can identify wasteful energy losses
      in biofuel production. More specifically, the study has examined the efficiency
      of six approaches for bioethanol production involving a sample of wheat, corn,
      cassava, and sweet potatoes as feedstocks and "old," "new," "wet," and "dry"
      processes. For each of these six bioethanol production pathways, the users can
      determine energy inputs such as the embodied energy for seed, machinery,
      fertilizer, diesel, chemicals and primary energy utilized for manufacturing, and
      outputs such as the energy content of the bioethanol and byproducts. The results
      indicate that DEA is a novel and feasible method for finding efficient bioethanol
      production scenarios and suggest that sweet potatoes may be the most energy
      efficient form of ethanol production for China. 

PMID- 24727399
TI  - The myosin motor domain-containing chitin synthase PdChsVII is required for
      development, cell wall integrity and virulence in the citrus postharvest pathogen
      Penicillium digitatum.
AB  - Chitin is an essential component of the fungal cell wall and a potential target
      in the development of new antifungal compounds, due to its presence in fungi and
      not in plants or vertebrates. Chitin synthase genes (chs) constitute a complex
      family in filamentous fungi and are involved in fungal development,
      morphogenesis, pathogenesis and virulence. In this study, additional chs genes in
      the citrus postharvest pathogen Penicillium digitatum have been identified.
      Comparative analyses included each PdChs in each one of the classes I to VII
      previously established, and support the grouping of these into three divisions.
      Disruption of the gene coding PdChsVII, which contains a short version of a
      myosin motor domain, has been achieved by using Agrobacterium tumefaciens
      mediated transformation and revealed its role in the life cycle of the fungus.
      Disruption strains were viable but showed reduced growth and conidia production.
      Moreover, Pdchs mutants developed morphological defects as balloon-like enlarged
      cells and increased chitin content, indicative of an altered cell wall structure.
      Gene disruption also increased susceptibility to antifungal compounds such as
      calcofluor white (CFW), sodium dodecyl sulfate (SDS), hydroxide peroxide (H2O2)
      and commercial fungicides, but significantly no change was observed in the
      sensitivity to antifungal peptides. The PdchsVII mutants were able to infect
      citrus fruit and produced tissue maceration, although had reduced virulence and
      most importantly were greatly impaired in the production of visible mycelium and
      conidia on the fruit. 

PMID- 24727400
TI  - Role of iNOS-NO-cGMP signaling in modulation of inflammatory and myelination
      processes.
AB  - Nitric oxide (NO) is the main activator of the soluble guanylate cyclase (sGC)
      guanosine 3'5' cyclic monophosphate (cGMP) pathway. The level of cGMP is
      regulated by phosphodiesterases (PDEs), which break down cGMP. It has been
      reported that levels of NO in the central nervous system (CNS) can greatly
      increase during demyelination and/or neuroinflammation. Controversially, in
      demyelination models, mice without iNOS may develop more severe cases of disease.
      Furthermore, cGMP accumulation caused by PDE inhibitors has an anti
      inflammatory/neuroprotective effect in MS-models. The role of the NO-cGMP pathway
      in the nervous tissue is, therefore, complex and not fully understood. The aim of
      the present study was to contribute to existing knowledge of the role of this
      pathway in the CNS. Wild type (WT - C57BL/6) and iNOS(-/-) animals were treated
      with sildenafil (25mg/kg) for 8 weeks. Control animals were not treated. VCAM and
      ICAM (adhesion proteins), GFAP and Iba-1 (astrocyte and microglia markers,
      respectively), PKG (cGMP-dependent protein kinase), sGC, eNOS (constitutive
      endothelial NO sinthase) and GSTpi (a marker of mature oligodendrocytes) were
      evaluated in the cerebellum using immunohistochemistry or western blotting.
      Myelin was assessed by luxol fast blue staining and electron transmission
      microscopy. Treatment with sildenafil reduced ICAM and VCAM levels (anti
      inflammatory effect) and increased GFAP and Iba-1 expression (clearance
      phenotype) in WT animals. The expression of VCAM, ICAM, GFAP, PKG and sGC was
      lower in iNOS(-/-) mice than in WT control animals. The treatment of iNOS(-/-)
      animals with sildenafil resulted in an increase of all proteins (pro-inflammatory
      effect). There was overexpression of eNOS in untreated iNOS(-/-) mice. The myelin
      structure of iNOS(-/-) animals was damaged in comparison with WT control.
      Sildenafil increased GSTpi and resulted in an improved myelin structure in iNOS(
      /-) mice. In conclusion, NO-cGMP signaling plays a role in the regulation of
      inflammation and myelination processes. The accumulation of cGMP produced
      opposite effects in WT and iNOS(-/-) mice. This can be explained by the
      overexpression of eNOS in iNOS(-/-) mice, unbalancing cGMP signaling, or cGMP has
      a dual role in inflammation. Drugs that modulate the NO-sGC-cGMP pathway may be
      clinically beneficial in the treatment of neuroinflammatory/demyelinating
      disorders, but further studies of the regulation of this pathway are required. 

PMID- 24727401
TI  - Optogenetics to study the circuits of fear- and depression-like behaviors: a
      critical analysis.
AB  - In recent years, the development and extensive use of optogenetics resulted in
      impressive findings on the neurobiology of anxiety and depression in animals.
      Indeed, it permitted to depict precisely the role of specific cell populations in
      various brain areas, including the amygdala nuclei, the auditory cortex, the
      anterior cingulate, the hypothalamus, the hippocampus and the bed nucleus of
      stria terminalis in specific aspects of fear and anxiety behaviors. Moreover,
      these findings emphasized the involvement of projections from the ventral
      tegmental area to the nucleus accumbens and the medial prefrontal cortex in
      eliciting depressive-like behaviors in stress-resilient mice or in inhibiting the
      expression of such behaviors in stress-vulnerable mice. Here we describe the
      optogenetic toolbox, including recent developments, and then review how the use
      of this technique contributed to dissect further the circuit underlying anxiety-
      and depression-like behaviors. We then point to some drawbacks of the current
      studies, particularly a) the sharp contrast between the sophistication of the
      optogenetic tools and the rudimentary aspect of the behavioral assays used, b)
      the fact that the studies were generally undertaken using normal rodents, that is
      animals that have not been subjected to experimental manipulations shifting them
      to a state relevant for pathologies and c) that the opportunity to explore the
      potential of these techniques to develop innovative therapeutics has been fully
      ignored yet. Finally, we discuss the point that these findings frequently ignore
      the complexity of the circuitry, as they focus only on a particular subpart of
      it. We conclude that users of this cutting edge technology could benefit from
      dialog between behavioral neuroscientists, psychiatrists and pharmacologists to
      further improve the impact of the findings. 

PMID- 24727402
TI  - Positive emotional arousal increases duration of memory traces: different role of
      dopamine D1 receptor and beta-adrenoceptor activation.
AB  - We investigated the effects of post-training administration of dopamine D1
      receptor antagonist SCH 23390 and beta-adrenergic receptor antagonist Propranolol
      on memory retention of an object sampled in a state of positive emotional
      arousal. Saline-treated mice trained and tested under high emotional/motivational
      arousal (High) showed discrimination of a novel object both 24 and 96 h post
      training. Instead, mice trained and tested under low motivational arousal (Low)
      were unable to discriminate the novel object 96 h post-training. Both a high (2
      mg/kg) and a low (1 mg/kg) dose of Propranolol reduced object discrimination in
      High mice tested 24 h post-training, whereas neither dose was effective in Low
      mice. A high dose of SCH 23390 (0.025 mg/kg) reduced discrimination of the novel
      object in High mice tested both 24 and 96 h post-training, whereas a low dose of
      the D1 antagonist (0.01 mg/kg) reduced discrimination in High mice tested 96 h
      post-training and abolished discrimination in Low mice tested 24h after training.

PMID- 24727403
TI  - Development of a FTIR-ATR based model for typing clinically relevant
      Acinetobacter baumannii clones belonging to ST98, ST103, ST208 and ST218.
AB  - In this work we developed and validated a FTIR-ATR (Fourier transform infrared
      spectroscopy with attenuated total reflectance) based model for typing
      Acinetobacter baumannii clinical isolates belonging to ST98, ST208 and ST218
      included into the worldwide spread clonal complex (CC) 92 and ST103. FTIR-ATR
      spectra of seventy-seven previously characterized isolates (Multi Locus Sequence
      Type-MLST, Pulsed-Field Gel Electrophoresis-PFGE and carbapenem-hydrolyzing class
      D beta-lactamase-CHDL) were acquired and modeled by partial least squares
      discriminant analysis (PLSDA). The model was tested and successfully validated
      with a diverse collection of isolates (n=148) recovered from different countries
      and periods of time belonging to modeled and non-modeled STs. 

PMID- 24727404
TI  - Anti-photoaging potential of Botulinum Toxin Type A in UVB-induced premature
      senescence of human dermal fibroblasts in vitro through decreasing senescence
      related proteins.
AB  - This study was aimed to evaluate the anti-photoaging effects of Botulinum Toxin
      Type A (BoNTA) in Ultraviolet B-induced premature senescence (UVB-SIPS) of human
      dermal fibroblasts (HDFs) in vitro and the underlying mechanism. We established a
      stress-induced premature senescence model by repeated subcytotoxic exposures to
      Ultraviolet B (UVB) irradiation. The aging condition was determined by
      cytochemical staining of senescence-associated beta-galactosidase (SA-beta-gal).
      The tumor suppressor and senescence-associated protein levels of p16(INK-4a),
      p21(WAF-1), and p53 were estimated by Western blotting. The G1 phase cell growth
      arrest was analyzed by flow cytometry. The mRNA expressions of p16, p21, p53,
      COL1a1, COL3a1, MMP1, and MMP3 were determined by real-time PCR. The level of Col
      1, Col-3, MMP-1, and MMP-3 were determined by ELISA. Compared with the UVB
      irradiated group, we found that the irradiated fibroblasts additionally treated
      with BoNTA demonstrated a decrease in the expression of SA-beta-gal, a decrease
      in the level of tumor suppressor and senescence-associated proteins, a decrease
      in the G1 phase cell proportion, an increase in the production of Col-1 and Col
      3, and a decrease in the secretion of MMP-1 and MMP-3, in a dose-dependent
      manner. Taken together, these results indicate that BoNTA significantly
      antagonizes premature senescence induced by UVB in HDFs in vitro, therefore
      potential of intradermal BoNTA injection as anti-photoaging treatment still
      remains a question. 

PMID- 24727406
TI  - Spectroscopical study of bacteriopurpurinimide-naphthalimide conjugates for
      fluorescent diagnostics and photodynamic therapy.
AB  - Two novel bis(chromophoric) dyads ABPI-NI1 and ABPI-NI2 containing 1,8
      naphthalimide and bacteriopurpurinimide units linked by p-phenylene-methylene
      (ABPI-NI1) and pentamethylene (ABPI-NI2) spacers were prepared to test their
      ability to be used in the design of effective agents for both photodynamic
      therapy (PDT) and fluorescent tumor imaging. Photophysical studies revealed that
      the emission from the naphthalimide chromophore in both conjugates was partially
      quenched due to resonance energy transfer between the photoactive components.
      Compound ABPI-NI2 with more sterically flexible oligomethylene group demonstrated
      higher fluorescence intensity as compared with that for ABPI-NI1. 

PMID- 24727405
TI  - Nano-sized layered Mn oxides as promising and biomimetic water oxidizing
      catalysts for water splitting in artificial photosynthetic systems.
AB  - One challenge in artificial photosynthetic systems is the development of
      artificial model compounds to oxidize water. The water-oxidizing complex of
      Photosystem II which is responsible for biological water oxidation contains a
      cluster of four Mn ions bridged by five oxygen atoms. Layered Mn oxides as
      efficient, stable, low cost, environmentally friendly and easy to use,
      synthesize, and manufacture compounds could be considered as functional and
      structural models for the site. Because of the related structure of these Mn
      oxides and the catalytic centre of the active site of the water oxidizing complex
      of Photosystem II, the study of layered Mn oxides may also help to understand
      more about the mechanism of water oxidation by the natural site. This review
      provides an overview of the current status of layered Mn oxides in artificial
      photosynthesis and discuss the sophisticated design strategies for Mn oxides as
      water oxidizing catalysts. 

PMID- 24727407
TI  - Assessment of radiation doses in the UK from the Fukushima Daiichi Nuclear
      accident.
AB  - PHE has undertaken a simple dose assessment for members of the public living in
      the UK at the time of the accident at the Fukushima Daiichi nuclear power station
      in March 2011. PHE reported that there was no public health risk to the UK from
      the release of material from the accident in a statement made on 29 March 2013.
      This assessment confirms the initial estimate of the doses which were about the
      same as a person in the UK would receive in an hour from natural background. 

PMID- 24727408
TI  - Intimate partner violence in rural U.S. areas: what every nurse should know.
AB  - Intimate partner violence is a major health care issue, affecting nearly 6% of
      U.S. women annually. Multiple mental and physical health problems are associated
      with intimate partner violence, and billions of health care dollars are spent in
      trying to address the consequences. Although prevalence rates of intimate partner
      violence are roughly the same in rural and nonrural areas, rural survivors face
      distinct barriers in obtaining help and services. Because rural women routinely
      access health care services in nonrural as well as rural settings, it's essential
      that all providers understand the issues specific to rural survivors. Routine
      screening for intimate partner violence would create opportunities for women to
      disclose abuse and for providers to help victims obtain assistance and support
      that may keep them safer. This in turn would likely decrease serious health
      sequelae and lower health care costs. This article describes the unique aspects
      of intimate partner violence in rural populations. It also describes a simple
      screening tool that can be used in all settings, discusses ways to approach the
      topic and facilitate disclosure, and addresses interventions; relevant resources
      are also provided.

PMID- 24727409
TI  - CE: Responding to the cholera epidemic in Haiti.
AB  - OVERVIEW: While Haiti was still recovering from the January 12, 2010, magnitude-7
      earthquake, an outbreak of cholera spread throughout the nation, soon reaching
      epidemic proportions. Working through the faith-based nongovernmental
      organization Samaritan's Purse, an NP, an epidemiologist, and a physician joined
      the effort to prevent the spread of disease and treat those affected. Here they
      describe the prevention and intervention campaigns their organization initiated,
      how they prepared for each, and the essential elements of their operations.

PMID- 24727410
TI  - Enabled clinical use of an HIV-1 attachment inhibitor through drug delivery.
AB  - The clinical advancement of HIV-1 attachment inhibitors was hindered initially by
      poor bioavailability. Attempts to identify improved candidates revealed that
      solubility and dissolution-rate-limited absorption are barriers to achieving
      adequate antiviral plasma levels. This was mitigated by forming nanosized drugs
      or by creating stabilised amorphous drug-polymer composites. In further improving
      drug potency and mitigating solubility-limited bioavailability, a candidate based
      on a phosphate ester prodrug was identified that, although having excellent
      bioavailability, exhibited unacceptable pharmacokinetics. Based on in silico
      modelling and a site of absorption study it was confirmed that creating an
      extended release formulation could provide the desired pharmacokinetic profile.
      The optimised formulation showed good antiviral activity when dosed employing a
      once or twice a day regimen. 

PMID- 24727411
TI  - Efferent projections of the suprachiasmatic nucleus based on the distribution of
      vasoactive intestinal peptide (VIP) and arginine vasopressin (AVP) immunoreactive
      fibers in the hypothalamus of Sapajus apella.
AB  - The suprachiasmatic nucleus (SCN), which is considered to be the master circadian
      clock in mammals, establishes biological rhythms of approximately 24 h that
      several organs exhibit. One aspect relevant to the study of the neurofunctional
      features of biological rhythmicity is the identification of communication
      pathways between the SCN and other brain areas. As a result, SCN efferent
      projections have been investigated in several species, including rodents and a
      few primates. The fibers originating from the two main intrinsic fiber
      subpopulations, one producing vasoactive intestinal peptide (VIP) and the other
      producing arginine vasopressin (AVP), exhibit morphological traits that
      distinguish them from fibers that originate from other brain areas. This
      distinction provides a parameter to study SCN efferent projections. In this
      study, we mapped VIP (VIP-ir) and AVP (AVP-ir) immunoreactive (ir) fibers and
      endings in the hypothalamus of the primate Sapajus apella via immunohistochemical
      and morphologic study. Regarding the fiber distribution pattern, AVP-ir and VIP
      ir fibers were identified in regions of the tuberal hypothalamic area,
      retrochiasmatic area, lateral hypothalamic area, and anterior hypothalamic area.
      VIP-ir and AVP-ir fibers coexisted in several hypothalamic areas; however, AVP-ir
      fibers were predominant over VIP-ir fibers in the posterior hypothalamus and
      medial periventricular area. This distribution pattern and the receiving
      hypothalamic areas of the VIP-ir and AVP-ir fibers, which shared similar
      morphological features with those found in SCN, were similar to the patterns
      observed in diurnal and nocturnal animals. This finding supports the conservative
      nature of this feature among different species. Morphometric analysis of SCN
      intrinsic neurons indicated homogeneity in the size of VIP-ir neurons in the SCN
      ventral portion and heterogeneity in the size of two subpopulations of AVP-ir
      neurons in the SCN dorsal portion. The distribution of fibers and morphometric
      features of these neuronal populations are described and compared with those of
      other species in the present study.

PMID- 24727412
TI  - Regulation of brain-type creatine kinase by AMP-activated protein kinase:
      interaction, phosphorylation and ER localization.
AB  - AMP-activated protein kinase (AMPK) and cytosolic brain-type creatine kinase
      (BCK) cooperate under energy stress to compensate for loss of adenosine
      triphosphate (ATP) by either stimulating ATP-generating and inhibiting ATP
      consuming pathways, or by direct ATP regeneration from phosphocreatine,
      respectively. Here we report on AMPK-dependent phosphorylation of BCK from
      different species identified by in vitro screening for AMPK substrates in mouse
      brain. Mass spectrometry, protein sequencing, and site-directed mutagenesis
      identified Ser6 as a relevant residue with one site phosphorylated per BCK dimer.
      Yeast two-hybrid analysis revealed interaction of active AMPK specifically with
      non-phosphorylated BCK. Pharmacological activation of AMPK mimicking energy
      stress led to BCK phosphorylation in astrocytes and fibroblasts, as evidenced
      with a highly specific phospho-Ser6 antibody. BCK phosphorylation at Ser6 did not
      affect its enzymatic activity, but led to the appearance of the phosphorylated
      enzyme at the endoplasmic reticulum (ER), close to the ER calcium pump, a
      location known for muscle-type cytosolic creatine kinase (CK) to support Ca2+
      pumping.

PMID- 24727413
TI  - Pharmacological evaluation of total alkaloids from nux vomica: effect of reducing
      strychnine contents.
AB  - The aim of the study was to investigate the possibility of improving the
      therapeutic efficacy of the total alkaloid fraction (TAF) extracted from
      processed nux vomica by reducing the strychnine contents. Most strychnine was
      removed from TAF to obtain the modified total alkaloid fraction (MTAF). The
      toxicity and pharmacokinetics of TAF and MTAF were further investigated and
      compared besides their antitumor, analgesic and anti-inflammatory activities. The
      results showed that the ratios of brucine to strychnine were 1:2.05 and 2.2:1 for
      TAF and MTAF, respectively, and the toxicity of TAF was about 3.17-fold higher
      than that of MTAF. Compared to brucine alone, the elimination of brucine was
      found to be inhibited by other alkaloids in TAF or MTAF except strychnine.
      Significantly increased pharmacological activities when administered by the oral
      route were obtained with MTAF in comparison to TAF and nux vomica powder (NVP).
      In summary, MTAF might replace NVP and TAF in the clinical application of Chinese
      medicine to obtain much higher efficacy. 

PMID- 24727414
TI  - HPLC-DPPH screening method for evaluation of antioxidant compounds extracted from
      Semen Oroxyli.
AB  - Semen Oroxyli, derived from the seed of Oroxylum indicum L., is a commonly used
      Traditional Chinese Medicine with beneficial effects against several respiratory
      disorders. Antioxidative flavonoids may be partly responsible for its medicinal
      functions. The aim of this study was to rapidly determine the antioxidants in
      Semen Oroxyli based on a HPLC-DPPH method. Four major flavonoids, baicalein-7-O
      gentiobioside, baicalein-7-O-glucoside, baicalein, and baicalin, were identified
      as the active components against DPPH free radicals, which is in accord with the
      results of our former traditional activity-guided phytochemical study. The
      oxidative products of the four antioxidant flavonoids were studied in the DPPH
      spiking HPLC assay, it was suggested that the three active flavonoid glycosides
      were converted into 5,6-dihydroxy-7-methoxyflavone, which implied that an
      additional hydroxyl at C-6 in 5,7-dihydroxyflavones plays an important role in
      the DPPH assay. 

PMID- 24727415
TI  - Synthesis of regiospecifically fluorinated conjugated dienamides.
AB  - Modular synthesis of regiospecifically fluorinated 2,4-diene Weinreb amides, with
      defined stereochemistry at both double bonds, was achieved via two sequential
      Julia-Kocienski olefinations. In the first step, a Z-a-fluorovinyl Weinreb amide
      unit with a benzothiazolylsulfanyl substituent at the allylic position was
      assembled. This was achieved via condensation of two primary building blocks,
      namely 2-(benzo[d]thiazol-2-ylsulfonyl)-2-fluoro-N-methoxy-N-methylacetamide (a
      Julia-Kocienski olefination reagent) and 2-(benzo[d]thiazol-2-ylthio)acetaldehyde
      (a bifunctional building block). This condensation was highly Z-selective and
      proceeded in a good 76% yield. Oxidation of benzothiazolylsulfanyl moiety
      furnished a second-generation Julia-Kocienski olefination reagent, which was used
      for the introduction of the second olefinic linkage via DBU-mediated
      condensations with aldehydes, to give (2Z,4E/Z)-dienamides in 50%-74% yield.
      Although olefinations were 4Z-selective, (2Z,4E/Z)-2-fluoro-2,4-dienamides could
      be readily isomerized to the corresponding 5-substituted (2Z,4E)-2-fluoro-N
      methoxy-N-methylpenta-2,4-dienamides in the presence of catalytic iodine. 

PMID- 24727416
TI  - The effect of chitin size, shape, source and purification method on immune
      recognition.
AB  - The animal immune response to chitin is not well understood and needs to be
      investigated further. However, this is a challenging topic to study because of
      the technical difficulties in purifying chitin, and because this material usually
      comes associated with contaminating components that can activate the immune
      system. In this study, improvements to previously described purification
      protocols were investigated for chitin obtained from different sources, including
      commercial shellfish, Candida albicans yeast and hyphal cell walls, as well as
      cell walls of the filamentous fungi Aspergillus fumigatus and Mucor
      circinelloides. The immune response to these different chitin preparations was
      tested using human peripheral blood mononuclear cells. In agreement with previous
      literature, small chitin particles of an average size of 0.2 um were not
      immunogenic. On the other hand, bigger chitin particles induced in some cases a
      pro-inflammatory response. The results of this work suggest that not only the
      purity and size of the chitin particles, but also their shape can influence
      immune recognition. 

PMID- 24727417
TI  - Multielemental composition of suet oil based on quantification by ultrawave/ICP
      MS coupled with chemometric analysis.
AB  - Suet oil (SO) has been used commonly for food and medicine preparation. The
      determination of its elemental composition has became an important challenge for
      human safety and health owing to its possible contents of heavy metals or other
      elements. In this study, ultrawave single reaction chamber microwave digestion
      (Ultrawave) and inductively coupled plasma-mass spectrometry (ICP-MS) analysis
      was performed to determine 14 elements (Pb, As, Hg, Cd, Fe, Cu, Mn, Ti, Ni, V,
      Sr, Na, Ka and Ca) in SO samples. Furthermore, the multielemental content of 18
      SO samples, which represented three different sources in China: Qinghai, Anhui
      and Jiangsu, were evaluated and compared. The optimal ultrawave digestion
      conditions, namely, the optimal time (35 min), temperature (210  degrees C) and
      pressure (90 bar), were screened by Box-Behnken design (BBD). Eighteen samples
      were successfully classified into three groups by principal component analysis
      (PCA) according to the contents of 14 elements. The results showed that all SO
      samples were rich in elements, but with significant differences corresponding to
      different origins. The outliers and majority of SO could be discriminated by PCA
      according to the multielemental content profile. The results highlighted that the
      element distribution was associated with the origins of SO samples. The proposed
      ultrawave digestion system was quite efficient and convenient, which could be
      mainly attributed to its high pressure and special high-throughput for the sample
      digestion procedure. Our established method could be useful for the quality
      control and standardization of elements in SO samples and products. 

PMID- 24727418
TI  - Quantitative analysis of the flavonoid glycosides and terpene trilactones in the
      extract of Ginkgo biloba and evaluation of their inhibitory activity towards
      fibril formation of beta-amyloid peptide.
AB  - The standard extract of Ginkgo biloba leaves (EGb761) is used clinically in
      Europe for the symptomatic treatment of impaired cerebral function in primary
      degenerative dementia syndromes, and the results of numerous in vivo and in vitro
      studies have supported such clinical use. The abnormal production and aggregation
      of amyloid beta peptide (Abeta) and the deposition of fibrils in the brain are
      regarded as key steps in the onset of Alzheimer's Disease (AD), and the
      inhibition of Abeta aggregation and destabilization of the preformed fibrils
      represent viable approaches for the prevention and treatment of AD. Flavonoid
      glycosides and terpene trilactones (TTLs) are the two main components of EGb761
      which represent 24 and 6% of the overall content, respectively. In our research,
      seven abundant flavonoid glycosides 1-7 were isolated from the extract of Ginkgo
      biloba leaves and characterized by spectroscopic analysis. Furthermore, an ultra
      high performance liquid chromatography method was established for the
      simultaneous quantification of these seven flavonoids. The inhibitory activities
      of these flavonoids, as well as four TTLs, i.e., ginkgolides A, B, and C and
      bilobalide (compounds 8-11), were evaluated towards Abeta42 fibril formation
      using a thioflavin T fluorescence assay. It was found that three flavonoids 1, 3
      and 4 exhibited moderate inhibitory activities, whereas the other four flavonoids
      2, 5, 6 and 7, as well as the four terpene trilactones, showed poor activity.
      This is the first report of the inhibition of Abeta fibril formation of two
      characteristic acylated flavonoid glycosides 6, 7 in Ginkgo leaves, on the basis
      of which the structure-activity relationship of these flavonoids 1-7 was
      discussed. 

PMID- 24727419
TI  - Studies on the bioactive flavonoids isolated from Pithecellobium clypearia Benth.
AB  - One new flavonoid named (2R,3R)-7-O-galloylplumbocatechin A (1) and three known
      flavonoids, (-)-5,3',4',5'-tetrahydroxyflavan-7-gallate (2), (+)-3,5,3',4',5'
      penta-hydroxyflavan-7-gallate (3), and (-)-7,4'-di-O-galloyltricetiflavan (4),
      were isolated from Pithecellobium clypearia Benth. Their structures were
      elucidated based on spectroscopic analysis, including homonuclear and
      heteronuclear correlation NMR (HSQC and HMBC) experiments. In vitro assays,
      compounds 1 and 2 showed moderate inhibitory effects against influenza H1N1 virus
      neuraminidase (NA). Compounds 1-4 were all found to inhibit the expression of
      proinflammatory cytokines IL-6 or MCP-1 induced by influenza H1N1 virus in human
      A549 lung carcinoma cells. 

PMID- 24727420
TI  - Inhibition and biochemical characterization of methicillin-resistant
      Staphylococcus aureus shikimate dehydrogenase: an in silico and kinetic study.
AB  - Methicillin-resistant Staphylococcus auerus (MRSA) strains are having a major
      impact worldwide, and due to their resistance to all beta-lactams, an urgent need
      for new drugs is emerging. In this regard, the shikimate pathway is considered to
      be one of the metabolic features of bacteria and is absent in humans. Therefore
      enzymes involved in this route, such as shikimate dehydrogenase (SDH), are
      considered excellent targets for discovery of novel antibacterial drugs. In this
      study, the SDH from MRSA (SaSDH) was characterized. The results showed that the
      enzyme is a monomer with a molecular weight of 29 kDa, an optimum temperature of
      65  degrees C, and a maximal pH range of 9-11 for its activity. Kinetic studies
      revealed that SDH showed Michaelis-Menten kinetics toward both substrates
      (shikimate and NADP+). Initial velocity analysis suggested that SaSDH catalysis
      followed a sequential random mechanism. Additionally, a tridimensional model of
      SaSDH was obtained by homology modeling and validated. Through virtual screening
      three inhibitors of SaSDH were found (compounds 238, 766 and 894) and their
      inhibition constants and mechanism were obtained. Flexible docking studies
      revealed that these molecules make interactions with catalytic residues. The data
      of this study could serve as starting point in the search of new chemotherapeutic
      agents against MRSA. 

PMID- 24727421
TI  - Different accumulation profiles of multiple components between pericarp and seed
      of Alpinia oxyphylla capsular fruit as determined by UFLC-MS/MS.
AB  - Plant secondary metabolites are known to not only play a key role in the
      adaptation of plants to their environment, but also represent an important source
      of active pharmaceuticals. Alpinia oxyphylla capsular fruits, made up of seeds
      and pericarps, are commonly used in traditional East Asian medicines. In clinical
      utilization of these capsular fruits, inconsistent processing approaches (i.e.,
      hulling pericarps or not) are employed, with the potential of leading to
      differential pharmacological effects. Therefore, an important question arises
      whether the content levels of pharmacologically active chemicals between the
      seeds and pericarps of A. oxyphylla are comparable. Nine secondary metabolites
      present in A. oxyphylla capsular fruits, including flavonoids (e.g.,
      tectochrysin, izalpinin, chrysin, apigenin-4',7-dimethylether and kaempferide),
      diarylheptanoids (e.g., yakuchinone A and B and oxyphyllacinol) and
      sesquiterpenes (e.g., nootkatone), were regarded as representative constituents
      with putative pharmacological activities. This work aimed to investigate the
      abundance of the nine constituents in the seeds and pericarps of A. oxyphylla.
      Thirteen batches of A. oxyphylla capsular fruits were gathered from different
      production regions. Accordingly, an ultra-fast high performance liquid
      chromatography/quadrupole tandem mass spectrometry (UFLC-MS/MS) method was
      developed and validated. We found that: (1) the nine secondary metabolites were
      differentially concentrated in seeds and fruit capsules; (2) nootkatone is
      predominantly distributed in the seeds; in contrast, the flavonoids and
      diarylheptanoids are mainly deposited in the capsules; and (3) the content levels
      of the nine secondary metabolites occurring in the capsules varied greatly among
      different production regions, although the nootkatone levels in the seeds were
      comparable among production regions. These results are helpful to evaluating and
      elucidating pharmacological activities of A. oxyphylla capsular fruits.
      Additionally, it may be of interest to elucidate the mechanisms involved in the
      distinct accumulation profiles of these secondary metabolites between seeds and
      pericarps. 

PMID- 24727422
TI  - Comparative study of tributyltin adsorption onto mesoporous silica functionalized
      with calix[4]arene, p-tert-butylcalix[4]arene and p-sulfonatocalix[4]arene.
AB  - The adsorption of tributyltin (TBT), onto three mesoporous silica adsorbents
      functionalized with calix[4]arene, p-tert-butylcalix[4]arene and p
      sulfonatocalix[4]arene (MCM-TDI-C4, MCM-TDI-PC4 and MCM-TDI-C4S, respectively)
      has been compared. Batch adsorption experiments were carried out and the effect
      of contact time, initial TBT concentration, pH and temperature were studied. The
      Koble-Corrigan isotherm was the most suitable for data fitting. Based on a
      Langmuir isotherm model, the maximum adsorption capacities were 12.1212, 16.4204
      and 7.5757 mg/g for MCM-TDI-C4, MCM-TDI-PC4 and MCM-TDI-C4S, respectively. The
      larger uptake and stronger affinity of MCM-TDI-PC4 than MCM-TDI-C4 and MCM-TDI
      C4S probably results from van der Waals interactions and the pore size
      distribution of MCM-TDI-PC4. Gibbs free energies for the three adsorption
      processes of TBT presented a negative value, reflecting that TBT/surface
      interactions are thermodynamic favorable and spontaneous. The interaction
      processes were accompanied by an increase of entropy value for MCM-TDI-C4 and MCM
      TDI-C4S (43.7192 and 120.7609 J/mol K, respectively) and a decrease for MCM-TDI
      PC4 (-37.4704 J/mol K). It is obviously observed that MCM-TDI-PC4 spontaneously
      adsorbs TBT driven mainly by enthalpy change, while MCM-TDI-C4 and MCM-TDI-C4S do
      so driven mainly by entropy changes. 

PMID- 24727423
TI  - Motor coordination uses external spatial coordinates independent of developmental
      vision.
AB  - The constraints that guide bimanual movement coordination are informative about
      the processing principles underlying movement planning in humans. For example,
      symmetry relative to the body midline benefits finger and hand movements
      independent of hand posture. This symmetry constraint has been interpreted to
      indicate that movement coordination is guided by a perceptual code. Although it
      has been assumed implicitly that the perceptual system at the heart of this
      constraint is vision, this relationship has not been tested. Here, congenitally
      blind and sighted participants made symmetrical and non-symmetrical (that is,
      parallel) bimanual tapping and finger oscillation movements. For both groups,
      symmetrical movements were executed more correctly than parallel movements,
      independent of anatomical constraints like finger homology and hand posture. For
      the blind, the reliance on external spatial factors in movement coordination
      stands in stark contrast to their use of an anatomical reference frame in
      perceptual processing. Thus, the externally coded symmetry constraint evident in
      bimanual coordination can develop in the absence of the visual system, suggesting
      that the visual system is not critical for the establishment of an external
      spatial reference frame in movement coordination. 

PMID- 24727424
TI  - Memory retrieval as a self-propagating process.
AB  - Retrieval of a subset of studied items and the presentation of those items as
      retrieval cues typically impair retrieval of the other items. Previous research
      on this self-limiting property of memory retrieval has relied heavily on short
      retention intervals and similar context between encoding and test. Here, we
      examined retrieval dynamics also after a prolonged retention interval with
      different spatial and social context between encoding and test, conditions that
      mimic people's remembering in many situations of daily life. For both unrelated
      word lists and more integrated prose material, we found retrieval and cuing to
      impair recall of other studied items after a short retention interval, but to
      improve recall in the prolonged retention interval condition. The results
      demonstrate that retrieval dynamics depend critically on situation, indicating
      that quite often in daily life, retrieval may be a self-propagating, rather than
      a self-limiting process. 

PMID- 24727425
TI  - Acute intermittent porphyria causes hepatic mitochondrial energetic failure in a
      mouse model.
AB  - Acute intermittent porphyria (AIP), an inherited hepatic disorder, is due to a
      defect of hydroxymethylbilane synthase (HMBS), an enzyme involved in heme
      biosynthesis. AIP is characterized by recurrent, life-threatening attacks at
      least partly due to the increased hepatic production of 5-aminolaevulinic acid
      (ALA). Both the mitochondrial enzyme, ALA synthase (ALAS) 1, involved in the
      first step of heme biosynthesis, which is closely linked to mitochondrial
      bioenergetic pathways, and the promise of an ALAS1 siRNA hepatic therapy in
      humans, led us to investigate hepatic energetic metabolism in Hmbs KO mice
      treated with phenobarbital. The mitochondrial respiratory chain (RC) and the
      tricarboxylic acid (TCA) cycle were explored in the Hmbs(-/-) mouse model. RC and
      TCA cycle were significantly affected in comparison to controls in mice treated
      with phenobarbital with decreased activities of RC complexes I (-52%,
      (**)p<0.01), II (-50%, (**)p<0.01) and III (-55%, (*)p<0.05), and decreased
      activity of alpha-ketoglutarate dehydrogenase (-64%, (*)p<0.05), citrate synthase
      (-48%, (**)p<0.01) and succinate dehydrogenase (-53%, (*)p<0.05). Complex II
      driven succinate respiration was also significantly affected. Most of these
      metabolic alterations were at least partially restored after the phenobarbital
      arrest and heme arginate administration. These results suggest a cataplerosis of
      the TCA cycle induced by phenobarbital, caused by the massive withdrawal of
      succinyl-CoA by ALAS induction, such that the TCA cycle is unable to supply the
      reduced cofactors to the RC. This profound and reversible impact of AIP on
      mitochondrial energetic metabolism offers new insights into the beneficial effect
      of heme, glucose and ALAS1 siRNA treatments by limiting the cataplerosis of TCA
      cycle. 

PMID- 24727426
TI  - Understanding how cystic fibrosis mutations disrupt CFTR function: from single
      molecules to animal models.
AB  - Defective epithelial ion transport is the hallmark of the life-limiting genetic
      disease cystic fibrosis (CF). This abnormality is caused by mutations in the
      cystic fibrosis transmembrane conductance regulator (CFTR), the ATP-binding
      cassette transporter that functions as a ligand-gated anion channel. Since the
      identification of the CFTR gene, almost 2000 disease-causing mutations associated
      with a spectrum of clinical phenotypes have been reported, but the majority
      remain poorly characterised. Studies of a small number of mutations including the
      most common, F508del-CFTR, have identified six general mechanisms of CFTR
      dysfunction. Here, we review selectively progress to understand how CF mutations
      disrupt CFTR processing, stability and function. We explore CFTR structure and
      function to explain the molecular mechanisms of CFTR dysfunction and highlight
      new knowledge of disease pathophysiology emerging from large animal models of CF.
      Understanding CFTR dysfunction is crucial to the development of transformational
      therapies for CF patients.

PMID- 24727427
TI  - Associations between primary healthcare and unplanned medical admissions in
      Norway: a multilevel analysis of the entire elderly population.
AB  - OBJECTIVE: To examine if individual risk of unplanned medical admissions (UMAs)
      was associated with municipality general practitioner (GP) or long-term care
      (LTC) volume among the entire Norwegian elderly population. DESIGN: Cross
      sectional population-based study. SETTING: 428 of 430 Norwegian municipalities in
      2009. PARTICIPANTS: All Norwegians aged >=65 years (n=721 915; 56% women-15% of
      the total population). MAIN OUTCOME MEASURE: Individual risk of UMA. RESULTS:
      Using a multilevel analytical framework, consisting of individuals (N=722 464)
      nested within municipalities (N=428), nested within local hospital areas (N=52)
      we found no association between municipality GP or LTC volume and UMAs. However,
      we found that higher LTC levels of provision were associated with fewer
      hospitalisations among the older age groups. A modest geographical variability
      was observed for UMA in adjusted analysis. CONCLUSIONS: A higher primary
      healthcare volume was only associated with fewer UMAs among the oldest old in a
      universally accessible healthcare system.

PMID- 24727428
TI  - Collaborative care for comorbid depression and diabetes: a systematic review and
      meta-analysis.
AB  - OBJECTIVE: The collaborative care model is recommended for depression in adults
      with a chronic physical health problem like diabetes. We sought to systematically
      assess the effect of collaborative care on depression and glycaemia in adults
      with comorbid depression and diabetes to inform guidelines and practice. DESIGN:
      Systematic review and meta-analysis. DATA SOURCES: We searched PubMed, Scopus,
      Cochrane Library, CINAHL, Health Source Nursing, MEDLINE, PsychINFO and reference
      lists of retrieved articles published before August 2013. INCLUSION CRITERIA:
      Randomised controlled trials (RCTs) on collaborative care (ie, coordinated
      multidisciplinary model of care) for depression that reported the effects on
      depression and glycaemic outcomes in adults with comorbid clinically relevant
      depression and diabetes were eligible. DATA EXTRACTION AND ANALYSIS: Data on the
      mean difference in depression and glycaemic outcomes were extracted and pooled
      using random effects meta-analysis. RESULTS: Seven RCTs included for review
      reported effects on depression outcomes in 1895 participants, and glycated
      haemoglobin (HbA1c) level in 1556 participants. Collaborative care significantly
      improved the depression score (standardised mean difference was -0.32 (95% CI 
      0.53 to -0.11); I(2)=79%) and HbA1c level (weighted mean difference was -0.33%
      (95% CI -0.66% to -0.00%); I(2)=72.9%) compared with control conditions.
      Depression remission did not predict better glycaemic control across studies.
      CONCLUSIONS: Limited evidence from short-to-medium term RCTs predominantly
      conducted in the USA suggests that collaborative care for depression
      significantly improves both depression and glycaemia outcomes, independently, in
      people with comorbid depression and diabetes.

PMID- 24727429
TI  - Isolation and identification of age-related DNA methylation markers for forensic
      age-prediction.
AB  - Age-prediction is an important part of forensic science. There is no available
      method of individual age-prediction for general forensic biological samples at
      crime scenes. Accumulating evidence indicates that aging resembles a
      developmentally regulated process tightly controlled by specific age-associated
      methylation exists in human genome. This study isolated and identified eight gene
      fragments in which the degree of cytosine methylation is significantly correlated
      with age in blood of 40 donors. Furthermore, we validated two CpG sites of each
      gene fragment and replicated our results in a general population sample of 40
      males and 25 females with a wide age-range (11-72 years). The methylation of
      these fragments is linear with age over a range of six decades (Fragment P1 (r=
      0.64), P2 (r=-0.58), P3 (r=-0.79), R1 (r=0.82), R2 (r=0.63), R3 (r=0.59), R4
      (r=0.63) and R5 (r=0.62)). Using average methylation of two CpG sites from each
      fragment, we built a regression model that explained 95% of the variance in age
      and is able to predict the age of an individual with great accuracy (R(2)=0.918).
      The predicted values are highly correlated with the observed age in the sample
      (r=0.91). This study implicates that DNA methylation will be an available
      biological marker of age-prediction. Furthermore, measurement of relevant sites
      in the genome could be a tool in routine forensic screening to predict age of
      biological samples. 

PMID- 24727430
TI  - Modelling PowerPlex(r) Y stutter and artefacts.
AB  - We have investigated the suitability of models used to predict expected stutter
      ratios and their variance developed for autosomal STR markers for application to
      Y STR markers. Models for expected back stutter, double back stutter, and forward
      stutter ratios for all loci in the PowerPlex((r)) Y multiplex and the heights of
      stutter-like artefacts at DYS19 and DYS385 are proposed. The longest
      uninterrupted stretch of repeats within an allele (LUS), marker and parent allele
      height was investigated as explanatory variables for stutter ratio and artefact
      height. The models are intended to be used within an expert system employing a
      continuous method of DNA interpretation. 

PMID- 24727431
TI  - DNA fingerprinting secondary transfer from different skin areas: Morphological
      and genetic studies.
AB  - The correct identification of the biological samples under analysis is crucial in
      forensic investigation in that it represents the pivotal issue attesting that the
      resulting genetic profiles are fully reliable in terms of weight of the evidence.
      The study reported herein shows that "touch DNA" secondary transfer is indeed
      possible from person to person and, in turn, from person to object depending on
      the specific sebaceous or non-sebaceous skin area previously touched. In
      addition, we demonstrate the presence of fragmented single stranded DNA
      specifically immunodetected in the vast majority of cells forming the sebaceous
      gland but not in the epidermis layers, strongly indicating that sebaceous fluid
      represents an important vector responsible for DNA transfer. In view of our
      results, forensic investigations need to take into account that the propensity to
      leave behind genetic material through contact could depend from the individual
      ability to shed sebaceous fluid on the skin surface. 

PMID- 24727432
TI  - Using continuous DNA interpretation methods to revisit likelihood ratio
      behaviour.
AB  - Continuous DNA interpretation systems make use of more information from DNA
      profiles than analysts have previously been able to with binary, threshold based
      systems. With these new continuous DNA interpretation systems and a new, more
      powerful, DNA profiling kit (GlobalFiler) there is an opportunity to re-examine
      the behaviour of a commonly used statistic in forensic science, the likelihood
      ratio (LR). The theoretical behaviour of the LR has been known for some time,
      although in many instances the behaviour has not been able to be thoroughly
      demonstrated due to limitations of the biological and mathematical models being
      used. In this paper the effects of profile complexity, replicate amplifications,
      assuming contributors, adding incorrect information, and adding irrelevant
      information to the calculation of the LR are explored. The empirical results are
      compared to theoretical expectations and explained. The work finishes with the
      results being used to dispel common misconceptions around reliability, accuracy,
      informativeness and reproducibility. 

PMID- 24727434
TI  - Nutritional knowledge of UK coaches.
AB  - Athletes obtain nutritional information from their coaches, yet their competency
      in this area is lacking. Currently, no research exists in the UK which has a
      different coach education system to many other countries. Therefore, the aim of
      this study was to evaluate the sports nutrition knowledge of UK coaching
      certificate (UKCC) level 2 and 3, hockey and netball qualified coaches. All
      coaches (n = 163) completed a sports nutrition questionnaire to identify: (a) if
      they provided nutritional advice; (b) their level of sport nutrition knowledge;
      and (c) factors that may have contributed to their level of knowledge. Over half
      the coaches provided advice to their athletes (n = 93, 57.1%), even though they
      were not competent to do so. Coaches responded correctly to 60.3 +/- 10.5% of all
      knowledge questions with no differences between those providing advice and those
      who did not (p > 0.05). Those coaches who had undertaken formal nutrition
      training achieved higher scores than those who had not (p < 0.05). In conclusion,
      UK sports coaches would benefit from continued professional development in sports
      nutrition to enhance their coaching practice. 

PMID- 24727433
TI  - The effects of alpha-tocopherol on bone: a double-edged sword?
AB  - Recent studies have found conflicting evidence on the role of alpha-tocopherol
      (alphaTF) on bone health. This nonsystematic review aimed to summarize the
      current evidence on the effects of alphaTF on bone health from cell culture,
      animal, and human studies in order to clarify the role of alphaTF on bone health.
      Our review found that alphaTF exerted beneficial, harmful or null effects on bone
      formation cells. Animal studies generally showed positive effects of alphaTF
      supplementation on bone in various models of osteoporosis. However, high-dose
      alphaTF was possibly detrimental to bone in normal animals. Human studies mostly
      demonstrated a positive relationship between alphaTF, as assessed using high
      performance liquid chromatography and/or dietary questionnaire, and bone health,
      as assessed using bone mineral density and/or fracture incidence. Three possible
      reasons high dosage of alphaTF can be detrimental to bone include its
      interference with Vitamin K function on bone, the blocking of the entry of other
      Vitamin E isomers beneficial to bone, and the role of alphaTF as a prooxidant.
      However, these adverse effects have not been shown in human studies. In
      conclusion, alphaTF may have a dual role in bone health, whereby in the
      appropriate doses it is beneficial but in high doses it may be harmful to bone.

PMID- 24727435
TI  - Activation of hindbrain neurons is mediated by portal-mesenteric vein
      glucosensors during slow-onset hypoglycemia.
AB  - Hypoglycemic detection at the portal-mesenteric vein (PMV) appears mediated by
      spinal afferents and is critical for the counter-regulatory response (CRR) to
      slow-onset, but not rapid-onset, hypoglycemia. Since rapid-onset hypoglycemia
      induces Fos protein expression in discrete brain regions, we hypothesized that
      denervation of the PMV or lesioning spinal afferents would suppress Fos
      expression in the dorsal medulla during slow-onset hypoglycemia, revealing a
      central nervous system reliance on PMV glucosensors. Rats undergoing PMV
      deafferentation via capsaicin, celiac-superior mesenteric ganglionectomy (CSMG),
      or total subdiaphragmatic vagotomy (TSV) were exposed to hyperinsulinemic
      hypoglycemic clamps where glycemia was lowered slowly over 60-75 min. In response
      to hypoglycemia, control animals demonstrated a robust CRR along with marked Fos
      expression in the area postrema, nucleus of the solitary tract, and dorsal motor
      nucleus of the vagus. Fos expression was suppressed by 65-92% in capsaicin
      treated animals, as was epinephrine (74%), norepinephrine (33%), and glucagon
      (47%). CSMG also suppressed Fos expression and CRR during slow-onset
      hypoglycemia, whereas TSV failed to impact either. In contrast, CSMG failed to
      impact upon Fos expression or the CRR during rapid-onset hypoglycemia. Peripheral
      glucosensory input from the PMV is therefore required for activation of hindbrain
      neurons and the full CRR during slow-onset hypoglycemia. 

PMID- 24727436
TI  - The siting of UK nuclear reactors.
AB  - Choosing a suitable site for a nuclear power station requires the consideration
      and balancing of several factors. Some 'physical' site characteristics, such as
      the local climate and the potential for seismic activity, will be generic to all
      reactors designs, while others, such as the availability of cooling water, the
      area of land required and geological conditions capable of sustaining the weight
      of the reactor and other buildings will to an extent be dependent on the
      particular design of reactor chosen (or alternatively the reactor design chosen
      may to an extent be dependent on the characteristics of an available site).
      However, one particularly interesting tension is a human and demographic one. On
      the one hand it is beneficial to place nuclear stations close to centres of
      population, to reduce transmission losses and other costs (including to the local
      environment) of transporting electricity over large distances from generator to
      consumer. On the other it is advantageous to place nuclear stations some distance
      away from such population centres in order to minimise the potential human
      consequences of a major release of radioactive materials in the (extremely
      unlikely) event of a major nuclear accident, not only in terms of direct exposure
      but also concerning the management of emergency planning, notably evacuation.This
      paper considers the emergence of policies aimed at managing this tension in the
      UK. In the first phase of nuclear development (roughly speaking 1945-1965) there
      was a highly cautious attitude, with installations being placed in remote rural
      locations with very low population density. The second phase (1965-1985) saw a
      more relaxed approach, allowing the development of AGR nuclear power stations
      (which with concrete pressure vessels were regarded as significantly safer)
      closer to population centres (in 'semi-urban' locations, notably at Hartlepool
      and Heysham). In the third phase (1985-2005) there was very little new nuclear
      development, Sizewell B (the first and so far only PWR power reactor in the UK)
      being colocated with an early Magnox station on the rural Suffolk coast. Renewed
      interest in nuclear new build from 2005 onward led to a number of sites being
      identified for new reactors before 2025, all having previously hosted nuclear
      stations and including the semi-urban locations of the 1960s and 1970s. Finally,
      some speculative comments are made as to what a 'fifth phase' starting in 2025
      might look like. 

PMID- 24727437
TI  - Contact inhibition modulates intracellular levels of miR-223 in a p27kip1
      dependent manner.
AB  - MicroRNAs (miRs) are a large class of small regulatory RNAs that function as
      nodes of signaling networks. This implicates that miRs expression has to be
      finely tuned, as observed during cell cycle progression. Here, using an
      expression profiling approach, we provide evidence that the CDK inhibitor p27Kip1
      regulates miRs expression following cell cycle exit. By using wild type and p27KO
      cells harvested in different phases of the cell cycle we identified several miRs
      regulated by p27Kip1 during the G1 to S phase transition. Among these miRs, we
      identified miR-223 as a miR specifically upregulated by p27Kip1 in G1 arrested
      cells. Our data demonstrate that p27Kip1 regulated the expression of miR-223, via
      two distinct mechanisms. p27Kip1 directly stabilized mature miR-223 expression,
      acting as a RNA binding protein and it controlled E2F1 expression that, in turn,
      regulated miR-223 promoter activity. The resulting elevated miR-223 levels
      ultimately participated to arresting cell cycle progression following contact
      inhibition. Importantly, this mechanism of growth control was conserved in human
      cells and deranged in breast cancers. Here, we identify a novel and conserved
      function of p27Kip1 that, by modulating miR-223 expression, contributes to proper
      regulation of cell cycle exit following contact inhibition. Thus we propose a new
      role for miR-223 in the regulation of breast cancer progression. 

PMID- 24727438
TI  - Two distinct arginine kinases in Neocaridina denticulate: psychrophilic and
      mesophilic enzymes.
AB  - The small shrimp Neocaridina denticulata has two types of arginine kinases (AKs):
      AK1 and AK2. We determined the full kinetic parameters for the forward reaction
      of the AKs at temperatures between 15 and 35 degrees C. The catalytic
      efficiencies, determined by kcat/(Ka(ATP).Kia(ARG)), of the two enzymes showed a
      marked difference in temperature dependence. The efficiency of AK2 decreased
      markedly with decreasing temperature, while that of AK1 did not decrease with
      decreasing temperature, suggesting that AK1 is a cold-adapted enzyme. This
      unusual characteristic of AK1 was attributable to the remarkable decrease in
      Kia(ARG) with decreasing temperature, which enlarges its catalytic efficiency.
      Criterion with the values of Delta(DeltaH(o?))p-m and Delta(TDeltaS(o?))p-m also
      indicate that AK1 is a psychrophilic enzyme and AK2 is mesophilic. 

PMID- 24727439
TI  - Efficacy and safety of selenium nanoparticles administered intraperitoneally for
      the prevention of growth of cancer cells in the peritoneal cavity.
AB  - Peritoneal implantation of cancer cells, particularly postoperative seeding
      metastasis, frequently occurs in patients with primary tumors in the stomach,
      colon, liver, and ovary. Peritoneal carcinomatosis is associated with poor
      prognosis. In this work, we evaluated the prophylactic effect of intraperitoneal
      administration of selenium (Se), an essential trace element and a putative
      chemopreventive agent, on peritoneal implantation of cancer cells. Elemental Se
      nanoparticles were injected into the abdominal cavity of mice, into which highly
      malignant H22 hepatocarcinoma cells had previously been inoculated. Se
      concentrations in the cancer cells and tissues, as well as the efficacy of
      proliferation inhibition and safety, were evaluated. Se was mainly concentrated
      in cancer cells compared to Se retention in normal tissues, showing at least an
      order of magnitude difference between the drug target cells (the H22 cells) and
      the well-recognized toxicity target of Se (the liver). Such a favorable selective
      distribution resulted in strong proliferation suppression without perceived host
      toxicity. The mechanism of action of the Se nanoparticle-triggered cytotoxicity
      was associated with Se-mediated production of reactive oxygen species, which
      impaired the glutathione and thioredoxin systems. Our results suggest that
      intraperitoneal administration of Se is a safe and effective means of preventing
      growth of cancer cells in the peritoneal cavity for the above-mentioned high-risk
      populations. 

PMID- 24727441
TI  - The connection of protein O-mannosyltransferase family to the biocontrol
      potential of Beauveria bassiana, a fungal entomopathogen.
AB  - O-Mannosylation dependent on the protein O-mannosyltransferase (Pmt) family is an
      essential post-translational modification process in eukaryotes, but their
      connection to the biocontrol potential of a filamentous entomopathogen against
      arthropod pests is not understood. Here, we characterized the functions of three
      Pmt orthologues (Pmt1, Pmt2 and Pmt4) in the Pmt family of Beauveria bassiana and
      found that they were positive, but differential, regulators of the fungal growth,
      conidiation, multi-stress tolerance and virulence. Three Pmt2 knockdown mutants
      (DeltaPmt2 was lethal), DeltaPmt1 and DeltaPmt4 grew 20-79% slower on nutrition
      rich and limited media. Their conidial yields on a standard medium were reduced
      by 17-62%, accompanied with delayed germination. All the mutants became
      significantly less tolerant to most stresses of cell wall perturbation, high
      osmolarity, oxidation, wet heat and UV-B irradiation during colony growth and
      conidial germination and lost virulence by 53-62% via cuticle infection, although
      their virulence via hemocoel injection was not affected. Strikingly, these
      phenotypic defects were accompanied with remarkable cell wall damage, including
      thinner cell wall, lower conidial hydrophobicity and altered cell wall
      composition. All the changes were well restored to wild-type levels by targeted
      Pmt1 or Pmt4 complementation. Our results indicate for the first time that Pmt1,
      Pmt2 and Pmt4 are all required for the full biocontrol potential of B. bassiana
      despite differential contributions. 

PMID- 24727440
TI  - Immunization with recombinantly expressed glycan antigens from Schistosoma
      mansoni induces glycan-specific antibodies against the parasite.
AB  - Schistosomiasis caused by infection with parasitic helminths of Schistosoma spp.
      is a major global health problem due to inadequate treatment and lack of a
      vaccine. The immune response to schistosomes includes glycan antigens, which
      could be valuable diagnostic markers and vaccine targets. However, no precedent
      exists for how to design vaccines targeting eukaryotic glycoconjugates. The di-
      and tri-saccharide motifs LacdiNAc (GalNAcbeta1,4GlcNAc; LDN) and fucosylated
      LacdiNAc (GalNAcbeta1,4(Fucalpha1-3)GlcNAc; LDNF) are the basis for several
      important schistosome glycan antigens. They occur in monomeric form or as
      repeating units (poly-LDNF) and as part of a variety of different
      glycoconjugates. Because chemical synthesis and conjugation of such antigens is
      exceedingly difficult, we sought to develop a recombinant expression system for
      parasite glycans. We hypothesized that presentation of parasite glycans on the
      cell surface would induce glycan-specific antibodies. We generated Chinese
      hamster ovary (CHO) Lec8 cell lines expressing poly-LDN (L8-GT) and poly-LDNF (L8
      GTFT) abundantly on their membrane glycoproteins. Sera from Schistosoma mansoni
      infected mice were highly cross-reactive with the cells and with cell-surface N
      glycans. Immunizing mice with L8-GT and L8-GTFT cells induced glycan-specific
      antibodies. The L8-GTFT cells induced a sustained booster response, with
      antibodies that bound to S. mansoni lysates and recapitulated the exquisite
      specificity of the anti-parasite response for particular presentations of LDNF
      antigen. In summary, this recombinant expression system promotes successful
      generation of antibodies to the glycans of S. mansoni, and it can be adapted to
      study the role of glycan antigens and anti-glycan immune responses in many other
      infections and pathologies. 

PMID- 24727443
TI  - The Psychosexual Impact of Partial and Total Breast Reconstruction: A Prospective
      One-Year Longitudinal Study.
AB  - BACKGROUND: This prospective trial sought to explore patients' satisfaction and
      expectations for surgery in the areas of sexuality and body image and to evaluate
      outcomes pertaining to sexual well-being after total and partial breast
      reconstruction (BR). METHODS: Patients who underwent mastectomy and immediate
      total BR (group 1; n = 60) or lumpectomy and reduction mammoplasty (group 2; n =
      10) completed a questionnaire preoperatively and 1 year postoperatively to assess
      their satisfaction with their sex life and body image, perceptions of breasts as
      a source of sexuality, and expectations of surgery in these areas. Surveys were
      scored on a 5-point Likert scale, with 5 indicating strongly agree. Change scores
      were evaluated in the 2 groups (P = 0.05). RESULTS: In group 1, satisfaction with
      sex life and body image was unchanged. Pursuit of sexual attractiveness (from
      3.78 to 3.31, P = 0.02) and an improved body image (from 3.89 to 3.33, P < 0.01)
      were cited as expectations for surgery but were achieved less often. When
      stratified by different types of reconstruction, there were no discernible
      differences in responses. In group 2, the patients reported an unexpected
      increase in their partner's perception of them as womanly (from 1.33 to 2.50, P =
      0.01) and greater gains in the ability to wear sexually provocative clothing
      (from 1.78 to 3.11, P < 0.01).Preoperative expectations for improved body image
      were more often met in group 2 than group 1 (from 3.60 to 4.00 vs from 3.89 to
      3.33, P = 0.02). Group 2 experienced greater improvement in body image
      satisfaction (from 2.80 to 3.80 vs from 3.37 to 3.44, P = 0.03). CONCLUSIONS:
      Overall satisfaction with sex life and body image was preserved for both groups;
      however, the oncoplastic approach achieved significantly larger gains in body
      image perception.

PMID- 24727444
TI  - How Does Volume of Resection Relate to Symptom Relief for Reduction Mammaplasty
      Patients?
AB  - BACKGROUND: Reduction mammaplasty surgery is well known to produce improvement in
      a wide range of symptoms associated with macromastia. Health care insurers
      frequently stipulate a minimum resection volume to qualify for coverage, limiting
      access to surgery for many. The authors aimed to identify whether small volume
      resections do produce symptomatic improvement, comparing preoperative and
      postoperative experience of symptoms across a range of tissue resection volumes.
      METHODS: Reduction mammaplasty patients were given a custom-designed
      questionnaire at routine postoperative follow-up appointments, asking them to
      rate their preoperative and postoperative experience of 9 symptoms related to
      macromastia. Results were compiled and analyzed alongside data from patient case
      notes. Of 661 patients identified as being eligible for inclusion in the study,
      410 had sufficiently complete data to proceed to statistical analysis. Patients
      were divided into 6 groups based on volume of breast tissue resected. A Schnur
      sliding scale percentile was also calculated for all patients. Statistical
      analysis of preoperative symptom prevalence and postoperative symptom change was
      carried out. Further analysis to examine for evidence of trend in symptom
      improvement across groups was implemented using the Jonckheere-Terpstra test for
      ordered alternatives. RESULTS: Patients who go on to have larger volumes of
      breast tissue resected were found to experience back pain, shoulder grooves,
      breast pain, rashes under the breast, exercise intolerance, and poor posture more
      frequently than those who go on to have smaller resections (P < 0.0005 for all).
      However, across the range of resection volumes, preoperatively symptomatic
      patients experienced significant improvement in several symptoms. Results
      suggested that a larger resection volume may correspond with greater improvement
      in back pain, neck pain, and poor posture. CONCLUSIONS: We found that reduction
      mammaplasty has a positive impact on a range of symptoms, even with lower volume
      resections and regardless of body surface area-calculated adjustments. This adds
      further weight to the argument that patients should not be denied access to the
      surgery based on arbitrary volume restrictions. We advocate freedom for the
      surgeon to make a decision on potential benefits of surgery based around the
      needs of each individual patient.

PMID- 24727442
TI  - Differential expression of anti-glycan antibodies in schistosome-infected humans,
      rhesus monkeys and mice.
AB  - Schistosomiasis is a debilitating parasitic disease of humans, endemic in
      tropical areas, for which no vaccine is available. Evidence points to glycan
      antigens as being important in immune responses to infection. Here we describe
      our studies on the comparative humoral immune responses to defined schistosome
      type glycan epitopes in Schistosoma mansoni-infected humans, rhesus monkeys and
      mice. Rhesus anti-glycan responses over the course of infection were screened on
      a defined glycan microarray comprising semi-synthetic glycopeptides terminating
      with schistosome-associated or control mammalian-type glycan epitopes, as well as
      a defined glycan microarray of mammalian-type glycans representing over 400
      glycan structures. Infected rhesus monkeys generated a high immunoglobulin G
      (IgG) antibody response to the core xylose/core alpha3 fucose epitope of N
      glycans, which peaked at 8-11 weeks post infection, coinciding with maximal
      ability to kill schistosomula in vitro. By contrast, infected humans generated
      low antibody levels to this epitope. At 18 months following praziquantel therapy
      to eliminate the parasite, antibody levels were negligible. Mice chronically
      infected with S. mansoni generated high levels of anti-fucosylated LacdiNAc
      (GalNAcbeta1, 4(Fucalpha1, 3)GlcNAc) IgM antibodies, but lacked a robust response
      to the core xylose/core alpha3 fucose N-glycan antigens compared with other
      species studied, and their sera demonstrated an intermediate level of
      schistosomula killing in vitro. These differential responses to parasite glycan
      antigens may be related to the ability of rhesus monkeys to self-cure in contrast
      to the chronic infection seen in humans and mice. Our results validate defined
      glycan microarrays as a useful technology to evaluate diagnostic and vaccine
      antigens for schistosomiasis and perhaps other infections. 

PMID- 24727445
TI  - Modeling fade patterns of nipple areola complex tattoos following breast
      reconstruction.
AB  - BACKGROUND: Nipple-areolar complex (NAC) tattoos are an effective cosmetic
      solution for creating a finished look following breast reconstruction procedures.
      NAC tattoos are prone to significant fading, leading patients to seek revisions.
      This study was designed to quantify changes in NAC tattoo appearance over time.
      METHODS: A total of 71 images of 39 patients were analyzed for NAC tattoo color
      and shape by 5 blinded medical student graders using a customized scoring system.
      Subsequently, each image was analyzed using ColorPic software (Iconico, New York,
      NY). Red/green/blue and hue/saturation/value color parameters were collected.
      Color quantities were normalized to the individual patient's skin tone to control
      for variability in lighting. Spearman correlations and nonlinear regressions were
      calculated utilizing GraphPad Prism 6.0 (GraphPad, La Jolla, CA). RESULTS: The
      length of time after tattoo placement inversely correlated with color score (P <
      0.0001) and shape score (P = 0.0007). The time following tattoo placement was
      also inversely correlated with all quantitative color parameters. Each color
      parameter fit a 1-phase exponential decay model. CONCLUSIONS: The decline in
      qualitative color and shape score agrees with clinical experience of tattoo
      quality declining over time. The color qualities of the tattoo approach those of
      the patient's skin over time, ultimately reaching a plateau. This can be modeled
      using a 1-phase decay equation. In practice, tattoo colors may be selected that
      compensate for the predictable changes that will occur. The results of this study
      will help optimize tattoo color and may alleviate the need for NAC tattoo
      revisions.

PMID- 24727446
TI  - Ankle Plantar-Flexion Contracture Complication After Aesthetic Calf Volume
      Reduction Procedure.
AB  - Minimally invasive, aesthetic calf volume reduction procedures are considered to
      be relatively safe. Published complications are mostly transient, with minimal
      functional loss. We hereby report debilitating ankle plantar-flexion contracture
      after aesthetic calf volume reduction procedure by selective neurectomy, with
      magnetic resonance imaging analysis and surgical treatment outcomes of this
      complication. From 2009 to 2010, 11 patients (17 lower legs) were surgically
      treated for this complication. The average preoperative ankle contracture angle
      of all involved lower legs was -22 degrees (range, -5 to -30 degrees). Magnetic
      resonance imaging performed in 14 lower legs showed lesions indicative of
      denervation atrophy, with fibrotic lesions causing longitudinal shortening of the
      gastrocnemius muscle. Of the 17 ankle contractures, 15 Silfverskiold test
      positive cases received miniopen gastrocnemius release, whereas 2 Silfverskiold
      test-negative cases received Achilles tendon lengthening by percutaneous triple
      hemiresection. At last follow-up, the dorsiflexion angle of all ankles improved
      to an average of 25 degrees (range, 20-30 degrees) with full plantar flexion in
      all patients, whereas the American Orthopaedic Foot and Ankle Society Ankle
      Hindfoot Scale scores improved from an average of 59.2 to 94.2. Surgeons and
      patients alike should be aware of debilitating ankle planter flexion contractures
      after aesthetic calf volume reduction procedures. Using minimally invasive
      gastrocnemius and Achilles tendon release, we were able to provide symptomatic
      and functional relief from this complication with minimal cosmetic sacrifice. 

PMID- 24727447
TI  - Venous thromboembolism prophylaxis in the massive weight loss patient: relative
      risk of bleeding.
AB  - BACKGROUND: Measures that can reduce the incidence of venous thromboembolism
      (VTE) are of great clinical importance. In addition to the use of sequential
      compression devices (SCDs), chemoprophylaxis with low-molecular-weight heparin
      (LMWH) has been recommended by the American College of Chest Physicians for major
      general surgery procedures. There remains inconclusive evidence to support
      guidelines for the plastic surgery population, and some surgeons hesitate to use
      anticoagulation due to concerns about bleeding in broad planes of dissection. The
      purpose of this study was to evaluate the risk of postoperative complications
      secondary to chemical thromboprophylaxis in massive weight loss patients.
      METHODS: Five hundred forty-six surgical cases were enrolled in an institutional
      review board-approved prospective clinical database in the 2 years before and
      after routine LMWH use was initiated. Inclusion required weight loss of greater
      than 50 lb. Group 1 had SCDs only (n = 334), whereas group 2 had SCDs and LMWH 6
      hours postoperatively (n = 212). Risk of VTE was calculated and complications of
      LMWH administration were analyzed. RESULTS: The overall risk of deep venous
      thrombosis and pulmonary embolism was 0.18%. There was no statistical difference
      between the groups (P > 0.05). Overall risk of hematoma was 5.4%, in concordance
      with the literature. There was no difference in hematoma risk between the groups
      (4.6% before and 6.6% after LMWH; P = 0.3). The transfusion rate was 8.5% before
      use of LMWH (group 1) and 7.6% after (group 2; P = 0.7). CONCLUSIONS: Strategies
      to reduce VTE rates remain important in all areas of plastic surgery. We have
      demonstrated no increased risk of transfusion or hematoma and a low overall
      incidence of VTE after implementing a chemoprophylaxis regimen. Postoperative
      LMWH can provide an excellent balance between VTE prophylaxis and the risk of
      bleeding complications.

PMID- 24727448
TI  - Differences in FOXP3 and CD127 expression in Treg-like cells in patients with
      IPEX syndrome.

PMID- 24727449
TI  - DDX4 (DEAD box polypeptide 4) colocalizes with cancer stem cell marker CD133 in
      ovarian cancers.
AB  - DDX4 (DEAD box polypeptide 4), characterized by the conserved motif Asp-Glu-Ala
      Asp (DEAD), is an RNA helicase which is implicated in various cellular processes
      involving the alteration of RNA secondary structure, such as translation
      initiation, nuclear and mitochondrial splicing, and ribosome and spliceosome
      assembly. DDX4 is known to be a germ cell-specific protein and is used as a
      sorting marker of germline stem cells for the production of oocytes. A recent
      report about DDX4 in ovarian cancer showed that DDX4 is overexpressed in
      epithelial ovarian cancer and disrupts a DNA damage-induced G2 checkpoint. We
      investigated the relationship between DDX4 and ovarian cancer stem cells by
      analyzing the expression patterns of DDX4 and the cancer stem cell marker CD133
      in ovarian cancers via tissue microarray. Both DDX4 and CD133 were significantly
      increased in ovarian cancer compared to benign tumors, and showed similar
      patterns of expression. In addition, DDX4 and CD133 were mostly colocalized in
      various types of ovarian cancer tissues. Furthermore, almost all CD133 positive
      ovarian cancer cells also express DDX4 whereas CD133-negative cells did not
      possess DDX4, suggesting a strong possibility that DDX4 plays an important role
      in cancer stem cells, and/or can be used as an ovarian cancer stem cell marker. 

PMID- 24727450
TI  - Secreted type of amyloid precursor protein induces glial differentiation by
      stimulating the BMP/Smad signaling pathway.
AB  - Alzheimer's disease (AD) is one of the most common neurodegenerative diseases
      leading to dementia. Although cytotoxicity of amyloid beta peptides has been
      intensively studied within pathophysiology of AD, the physiological function of
      amyloid precursor protein (APP) still remains unclarified. We have shown
      previously that secreted APPalpha (sAPPalpha) is associated with glial
      differentiation of neural stem cells. To elucidate specific mechanisms underlying
      sAPPalpha-induced gliogenesis, we examined the potential involvement of bone
      morphogenic proteins (BMPs). BMPs are one of the factors involved in glial
      differentiation of neural progenitor cells. When expressions of BMP-2, -4, and -7
      were examined, upregulation of BMP-4 expression was solely observed as a result
      of treatment with sAPPalpha in a time and dose-dependent manner. Furthermore, the
      treatment of sAPPalpha promoted phosphorylation of Smad1/5/8, a downstream
      signaling mediator of BMP receptors. Interestingly, N-terminal domain of APP (1
      205) was sufficient to elevate BMP4 expression, resulting in an increase of glial
      fibrillary acidic protein (GFAP) expression and phosphorylation of Smad1/5/8.
      However, the application of APP neutralizing antibody and anti-BMP4 antibody
      significantly suppressed expression of BMP-4 as well as phosphorylation of
      Smad1/5/8. Thus, our results indicate that sAPPalpha-induced gliogenesis is in
      part mediated by the BMP-4 signaling pathway. We also observed upregulation of
      BMP-4 and phosphorylation of Smad1/5/8 in APP transgenic mice. It is imperative
      to unravel the mechanisms underlying the role of BMP-4 during APPalpha-induced
      glial differentiation in hope of providing novel prevention or treatment for AD.

PMID- 24727451
TI  - EGFR trans-activation mediates pleiotrophin-induced activation of Akt and Erk in
      cultured osteoblasts.
AB  - Pleiotrophin (Ptn) plays an important role in bone growth through regulating
      osteoblasts' functions. The underlying signaling mechanisms are not fully
      understood. In the current study, we found that Ptn induced heparin-binding
      epidermal growth factor (HB-EGF) release to trans-activate EGF-receptor (EGFR) in
      both primary osteoblasts and osteoblast-like MC3T3-E1 cells. Meanwhile, Ptn
      activated Akt and Erk signalings in cultured osteoblasts. The EGFR inhibitor
      AG1478 as well as the monoclonal antibody against HB-EGF (anti-HB-EGF)
      significantly inhibited Ptn-induced EGFR activation and Akt and Erk
      phosphorylations in MC3T3-E1 cells and primary osteoblasts. Further, EGFR siRNA
      depletion or dominant negative mutation suppressed also Akt and Erk activation in
      MC3T3-E1 cells. Finally, we observed that Ptn increased alkaline phosphatase
      (ALP) activity and inhibited dexamethasone (Dex)-induced cell death in both MC3T3
      E1 cells and primary osteoblasts, such effects were alleviated by AG1478 or anti
      HB-EGF. Together, these results suggest that Ptn-induced Akt/Erk activation and
      some of its pleiotropic functions are mediated by EGFR trans-activation in
      cultured osteoblasts.

PMID- 24727452
TI  - Polyethyleneimine-coating enhances adenoviral transduction of mesenchymal stem
      cells.
AB  - Mesenchymal stem cells (MSCs) are non-hematopoietic cells with multi-lineage
      potential, which makes them attractive targets for regenerative medicine
      applications. Efficient gene transfer into MSCs is essential for basic research
      in developmental biology and for therapeutic applications involving gene
      modification in regenerative medicine. Adenovirus vectors (Advs) can efficiently
      and transiently introduce an exogenous gene into many cell types via their
      primary receptors, the coxsackievirus and adenovirus receptors (CARs), but not
      into MSCs, which lack CAR expression. To overcome this problem, an Adv coated
      with cationic polymer polyethyleneimine (PEI) was developed. In this study, we
      demonstrated that PEI coating with an optimal ratio can enhance adenoviral
      transduction of MSCs without cytotoxicity. We also investigated the
      physicochemical properties and internalization mechanisms of the PEI-coated Adv.
      These results could help to evaluate the potentiality of the PEI-coated Adv as a
      prototype vector for efficient and safe transduction into MSCs. 

PMID- 24727453
TI  - The E3 ligase RNF185 negatively regulates osteogenic differentiation by targeting
      Dvl2 for degradation.
AB  - Osteoblast plays a pivotal role in bone metabolism and bone remodeling by
      mediating bone formation and regulating the activity of osteoclast. Clarifying
      the regulators and regulation mechanisms of osteogenic differentiation of
      mesenchymal stem cells (MSCs) and pre-osteoblasts will provide tremendous promise
      for bone repair and bone regeneration. RNF185 was identified as a candidate of
      endogenous suppressors of osteogenic specification in human mesenchymal stem
      cells (hMSCs). Here we show that RNF185 down regulates osteogenic differentiation
      of mouse calvaria-derived MC3T3-E1 cells, confirmed by quantitative real-time-PCR
      (qRT-PCR) and alkaline phosphatase (ALP) activity. Further we confirm that RNF185
      interacts with dishevelled2 (Dvl2), a key mediator of Wnt signaling pathway.
      Overexpression of RNF185 decreases the exogenous and endogenous level of Dvl2,
      promotes the ubiquitination and degradation of Dvl2 and inhibits Wnt signaling,
      which is evident from the down-regulation of beta-catenin mediated
      transcriptional activity. And Dvl2 reverses the effect of RNF185 on osteogenic
      differentiation of MC3T3-E1 cells. Taken together, our results indicate that
      RNF185 negatively regulates osteogenesis through the degradation of Dvl2 and down
      regulation of canonical Wnt signaling pathway and suggest a possible therapeutic
      target in osteoporosis.

PMID- 24727454
TI  - 3D microenvironment of collagen hydrogel enhances the release of neurotrophic
      factors from human umbilical cord blood cells and stimulates the neurite
      outgrowth of human neural precursor cells.
AB  - The umbilical cord blood (UCB) cells have been reported to secrete therapeutic
      signals, including a series of neurotrophic factors. This suggests the cell
      source provides suitable therapeutic environments for nerve regeneration that
      ultimately finds a possible cell therapy for nerve tissue. In this study, we
      observe a collagen hydrogel provides human UCB cells a proper 3D environment that
      stimulates the release of various neurotrophic factors. When compared to 2D
      culture, the 3D hydrogel culture significantly enhanced the expression of a
      series of neurotrophic factors, including neurotrophins, nerve growth factor,
      brain-derived neurotrophic factor, and ciliary neurotrophic factor as verified by
      the gene and protein analysis. To confirm the effects of neurotrophic factors
      secretion, we allowed an indirect interaction of the UCB-environment with human
      neural precursor cells (hNPCs). Results showed significantly enhanced neurite
      outgrowth of hNPCs. Collectively, our findings demonstrate that the collagen
      based 3D hydrogel provides excellent environment for UCB-derived cells to release
      neurotrophic factors that will be ultimately useful for the neural repair and
      regeneration purposes. 

PMID- 24727455
TI  - Identification of a genetic interaction between the tumor suppressor EAF2 and the
      retinoblastoma protein (Rb) signaling pathway in C. elegans and prostate cancer
      cells.
AB  - The tumor suppressor EAF2 is regulated by androgen signaling and associated with
      prostate cancer. While EAF2 and its partner ELL have been shown to be members of
      protein complexes involved in RNA polymerase II transcriptional elongation, the
      biologic roles for EAF2 especially with regards to the development of cancer
      remains poorly understood. We have previously identified the eaf-1 gene in
      Caenorhabditiselegans as the ortholog of EAF2, and shown that eaf-1 interacts
      with the ELL ortholog ell-1 to control development and fertility in worms. To
      identify genetic pathways that interact with eaf-1, we screened RNAi libraries
      consisting of transcription factors, phosphatases, and chromatin-modifying
      factors to identify genes which enhance the effects of eaf-1(tm3976) on
      fertility. From this screen, we identified lin-53, hmg-1.2, pha-4, ruvb-2 and set
      6 as hits. LIN-53 is the C. elegans ortholog of human retinoblastoma binding
      protein 4/7 (RBBP 4/7), which binds to the retinoblastoma protein and inhibits
      the Ras signaling pathway. We find that lin-53 showed a synthetic interaction
      with eaf-1(tm3976) where knockdown of lin-53 in an eaf-1(tm3976) mutant resulted
      in sterile worms. This phenotype may be due to cell death as the treated worms
      contain degenerated embryos with increased expression of the ced-1:GFP cell death
      marker. Further we find that the interaction between eaf-1 and lin-53/RBBP4/7
      also exists in vertebrates, which is reflected by the formation of a protein
      complex between EAF2 and RBBP4/7. Finally, overexpression of either human EAF2 or
      RBBP4 in LNCaP cells induced the cell death while knockdown of EAF2 in LNCaP
      enhanced cell proliferation, indicating an important role of EAF2 in controlling
      the growth and survival of prostate cancer cells. Together these findings
      identify a novel physical and functional interaction between EAF2 and the Rb
      pathway. 

PMID- 24727456
TI  - Adenosine induces apoptosis in human liver cancer cells through ROS production
      and mitochondrial dysfunction.
AB  - Mitochondria are the most important sensor for apoptosis. Extracellular adenosine
      is well reported to induce apoptosis of tumor cells. Here we found that
      extracellular adenosine suppresses the cell growth by induction of apoptosis in
      BEL-7404 liver cancer cells, and identified a novel mechanism that extracellular
      adenosine triggers apoptosis by increasing Reactive Oxygen Species (ROS)
      production and mitochondrial membrane dysfunction in the cells. We observed that
      adenosine increases ROS production, activates c-Caspase-8 and -9 and Caspase
      effectors, c-Caspase-3 and c-PARP, induces accumulation of apoptosis regulator
      Bak, decreases Bcl-xL and Mcl-1, and causes the mitochondrial membrane
      dysfunction and the release of DIABLO, Cytochrome C, and AIF from mitochondria to
      cytoplasm in the cells; ROS inhibitor, NAC significantly reduces adenosine
      induced ROS production; it also shows the same degree of blocking adenosine
      induced loss of mitochondrial membrane potential (MMP) and apoptosis. Our study
      first observed that adenosine increases ROS production in tumor cells and
      identified the positive feedback loop for ROS-mediated mitochondrial membrane
      dysfunction which amplifies the death signals in the cells. Our findings
      indicated ROS production and mitochondrial dysfunction play a key role in
      adenosine-induced apoptosis of 7404 cells.

PMID- 24727457
TI  - SUMO-modification and elimination of the active DNA demethylation enzyme TDG in
      cultured human cells.
AB  - Thymine DNA glycosylase (TDG) is a base excision repair enzyme that interacts
      with the small ubiquitin-related modifier (SUMO)-targeted ubiquitin E3 ligase
      RNF4 and functions in the active DNA demethylation pathway. Here we showed that
      both SUMOylated and non-modified forms of endogenous TDG fluctuated during the
      cell cycle and in response to drugs that perturbed cell cycle progression,
      including hydroxyurea and nocodazole. Additionally, we detected a SUMOylation
      independent association between TDG and RNF4 in vitro as well as in vivo, and
      observed that both forms of TDG were efficiently degraded in RNF4-depleted cells
      when arrested at S phase. Our findings provide insights into the in vivo dynamics
      of TDG SUMOylation and further clarify the TDG-RNF4 interaction.

PMID- 24727458
TI  - BAFF-R mutations in Good's syndrome.

PMID- 24727459
TI  - Amino Acid Prodrugs: An Approach to Improve the Absorption of HIV-1 Protease
      Inhibitor, Lopinavir.
AB  - Poor systemic concentrations of lopinavir (LPV) following oral administration
      occur due to high cellular efflux by P-glycoprotein (P-gp) and multidrug
      resistance-associated proteins (MRPs) and extensive metabolism by CYP3A4 enzymes.
      In this study, amino acid prodrugs of LPV were designed and investigated for
      their potential to circumvent efflux processes and first pass effects. Three
      amino acid prodrugs were synthesized by conjugating isoleucine, tryptophan and
      methionine to LPV. Prodrug formation was confirmed by the LCMS/MS and NMR
      technique. Interaction of LPV prodrugs with efflux proteins were carried out in P
      gp (MDCK-MDR1) and MRP2 (MDCK-MRP2) transfected cells. Aqueous solubility studies
      demonstrated that prodrugs generate higher solubility relative to LPV. Prodrugs
      displayed higher stability under acidic conditions and degraded significantly
      with rise in pH. Uptake and transport data suggested that prodrugs carry
      significantly lower affinity towards P-gp and MRP2 relative to LPV. Moreover,
      prodrugs exhibited higher liver microsomal stability relative to LPV. Hence,
      amino acid prodrug modification might be a viable approach for enhancing LPV
      absorption across intestinal epithelial and brain endothelial cells which
      expresses high levels of P-gp and MRP2. 

PMID- 24727460
TI  - Mitigating the risk of radiation-induced cancers: limitations and paradigms in
      drug development.
AB  - The United States radiation medical countermeasures (MCM) programme for
      radiological and nuclear incidents has been focusing on developing mitigators for
      the acute radiation syndrome (ARS) and delayed effects of acute radiation
      exposure (DEARE), and biodosimetry technologies to provide radiation dose
      assessments for guiding treatment. Because a nuclear accident or terrorist
      incident could potentially expose a large number of people to low to moderate
      doses of ionising radiation, and thus increase their excess lifetime cancer risk,
      there is an interest in developing mitigators for this purpose. This article
      discusses the current status, issues, and challenges regarding development of
      mitigators against radiation-induced cancers. The challenges of developing
      mitigators for ARS include: the long latency between exposure and cancer
      manifestation, limitations of animal models, potential side effects of the
      mitigator itself, potential need for long-term use, the complexity of human
      trials to demonstrate effectiveness, and statistical power constraints for
      measuring health risks (and reduction of health risks after mitigation) following
      relatively low radiation doses (<0.75 Gy). Nevertheless, progress in the
      understanding of the molecular mechanisms resulting in radiation injury, along
      with parallel progress in dose assessment technologies, make this an opportune,
      if not critical, time to invest in research strategies that result in the
      development of agents to lower the risk of radiation-induced cancers for
      populations that survive a significant radiation exposure incident. 

PMID- 24727461
TI  - Hydroxytyrosol ameliorates oxidative stress and mitochondrial dysfunction in
      doxorubicin-induced cardiotoxicity in rats with breast cancer.
AB  - Oxidative stress is involved in several processes including cancer, aging and
      cardiovascular disease, and has been shown to potentiate the therapeutic effect
      of drugs such as doxorubicin. Doxorubicin causes significant cardiotoxicity
      characterized by marked increases in oxidative stress and mitochondrial
      dysfunction. Herein, we investigate whether doxorubicin-associated chronic
      cardiac toxicity can be ameliorated with the antioxidant hydroxytyrosol in rats
      with breast cancer. Thirty-six rats bearing breast tumors induced chemically were
      divided into 4 groups: control, hydroxytyrosol (0.5mg/kg, 5days/week),
      doxorubicin (1mg/kg/week), and doxorubicin plus hydroxytyrosol. Cardiac
      disturbances at the cellular and mitochondrial level, mitochondrial electron
      transport chain complexes I-IV and apoptosis-inducing factor, and oxidative
      stress markers have been analyzed. Hydroxytyrosol improved the cardiac
      disturbances enhanced by doxorubicin by significantly reducing the percentage of
      altered mitochondria and oxidative damage. These results suggest that
      hydroxytyrosol improve the mitochondrial electron transport chain. This study
      demonstrates that hydroxytyrosol protect rat heart damage provoked by doxorubicin
      decreasing oxidative damage and mitochondrial alterations. 

PMID- 24727462
TI  - Synthesis of 6-cinnamoyl-2H-benzo[b][1,4]oxazin-3(4H)-ones and their effects on
      A549 lung cancer cell growth.
AB  - A series of novel 6-cinnamoyl-2H-benzo[b][1,4]oxazin-3(4H)-one derivatives was
      synthesized. The structures of compounds were characterized by (1)H NMR, IR, and
      MS. Moreover, representative crystal structure was determined by X-ray
      diffraction analysis. The preliminary biological evaluation of all these
      compounds showed that compounds 3a-3d would suppress the growth of A549 lung
      cells effectively by inducing autophagy and cell cycle arrest. 

PMID- 24727463
TI  - In-vitro anti-proliferative and anti-oxidant activity of galangin, fisetin and
      quercetin: role of localization and intermolecular interaction in model membrane.
AB  - Flavonols are an important class of naturally occurring molecules and are known
      for their pharmacological activity. The activity is associated with the ability
      of flavonols to influence membrane-dependent processes. We have investigated the
      in-vitro anti-proliferative and anti-oxidant activity of galangin (GLN), fisetin
      (FTN) and quercetin (QTN), which possess variable number of phenolic hydroxyl
      groups. An attempt has been made to correlate the biological activity of these
      molecules with their interaction and localization in dipalmitoyl phosphatidyl
      choline (DPPC) bilayers, using differential dcanning calorimetry (DSC) and
      nuclear magnetic resonance (NMR) methods. Results indicate that GLN interacts to
      the alkyl chains of the lipid bilayer involving hydrophobic interactions. FTN and
      QTN interact with head region and sn-1-glycero region involving hydrogen bonding.
      Ring current induced chemical shifts of lipid protons, due to intermolecular
      interaction indicate that GLN acquires a parallel orientation with respect to the
      bilayer normal whereas FTN and QTN resume a mixed orientation. The membrane
      binding constants of these molecules are in the order GLN > QTN > FTN. It has
      been shown that the number and position of hydroxyl groups in these molecules
      play an important role in membrane binding and thereby in biological activity. 

PMID- 24727464
TI  - Novel R-(+)-limonene-based thiosemicarbazones and their antitumor activity
      against human tumor cell lines.
AB  - In an attempt to develop potent and selective antitumor agents, a series of novel
      thiosemicarbazones derived from a natural monoterpene R-(+)-limonene was
      synthesized and their antitumor activity was evaluated. Overall, the majority of
      tested compounds exhibited considerable inhibitory effects on the growth of a
      wide range of cancer cell lines. Almost all of tested thiosemicarbazones were
      especially sensitive to prostate cells (PC-3). Derivatives 5, 6, 8, 9, 10, 11 and
      13 presented the most potent antitumor activity against PC-3 cells. These
      compounds showed lower value of GI50 (0.04-0.05 MUM) than the reference drug
      paclitaxel, besides a high selectivity for the same cell line. The 4
      fluorobenzaldehyde derivative 10 was the most selective compound for prostate
      cells, while 2-hydroxybenzaldehyde derivative 8 was the most active compound,
      with potent antitumor activity against all tested cell lines. 

PMID- 24727465
TI  - Picolinic acid based Cu(II) complexes with heterocyclic bases--crystal structure,
      DNA binding and cleavage studies.
AB  - In view of the importance of picolinic acid (PA) in preventing cell growth and
      arresting cell cycle, new PA based metallonucleases were designed with a view to
      study their DNA binding and cleavage abilities. Three new Cu(II) complexes
      [Cu(II)(DPPA)].4H2O (1),[Cu(II)(DPPA)(bpy)].5H2O (2) and
      [Cu(II)(DPPA)(phen)].5H2O (3), were synthesized using a picolinic acid based
      bifunctional ligand (DPPA) and heterocyclic bases (where DPPA: Pyridine-2
      carboxylic acid {2-phenyl-1-[(pyridin-2-ylmethyl)-carbonyl]-ethyl}-amide; bpy: 2,
      2'-bipyridine and phen: 1, 10-phenanthroline). DPPA was obtained by coupling 2
      picolinic acid and 2-picolyl amine with l-phenylalanine through amide bond??.
      Complexes were structurally characterized by a single crystal X-ray
      crystallography. The molecular structure of 1 shows Cu(II) center essentially in
      a square planar coordination geometry, while complex 2 shows an approximate five
      coordinated square-pyramidal geometry. Eventhough we could not isolate single
      crystal for complex (3), its structure was established based on other techniques.
      The complex (3) also exhibits five coordinate square pyramidal geometry. The
      complexes show good binding affinity towards CT-DNA. The binding constants (Kb)
      decrease in the order 1.35 +/- 0.01 * 10(5) (3) > 1.23 +/- 0.01 * 10(5) (2) > 8.3
      +/- 0.01 * 10(4) (1) M(-1). They also exhibit efficient nuclease activity towards
      supercoiled pUC19 DNA both in the absence and presence of external agent (H2O2).
      The kinetic studies reveal that the hydrolytic cleavage reactions follow the
      pseudo first-order rate constant and the hydrolysis rates are in the range of
      (5.8-8.0) * 10(7) fold rate enhancement compared to non-catalyzed double stranded
      DNA (3.6 * 10(-8) h(-1)). 

PMID- 24727466
TI  - Diagnostic accuracy of microEEG: a miniature, wireless EEG device.
AB  - Measuring the diagnostic accuracy (DA) of an EEG device is unconventional and
      complicated by imperfect interrater reliability. We sought to compare the DA of a
      miniature, wireless, battery-powered EEG device ("microEEG") to a reference EEG
      machine in emergency department (ED) patients with altered mental status (AMS).
      Two hundred twenty-five ED patients with AMS underwent 3 EEGs. Two EEGs, EEG1
      (Nicolet Monitor, "reference") and EEG2 (microEEG) were recorded simultaneously
      with EEG cup electrodes using a signal splitter. The remaining study, EEG3, was
      recorded with microEEG using an electrode cap immediately before or after
      EEG1/EEG2. The official EEG1 interpretation was considered the gold standard
      (EEG1-GS). EEG1, 2, and 3 were de-identified and blindly interpreted by two
      independent readers. A generalized mixed linear model was used to estimate the
      sensitivity and specificity of these interpretations relative to EEG1-GS and to
      compute a diagnostic odds ratio (DOR). Seventy-nine percent of EEG1-GS were
      abnormal. Neither the DOR nor the kappaf representing interrater reliabilities
      differed significantly between EEG1, EEG2, and EEG3. The mean setup time was 27
      min for EEG1/EEG2 and 12 min for EEG3. The mean electrode impedance of EEG3
      recordings was 12.6 kOmega (SD: 31.9 kOmega). The diagnostic accuracy of microEEG
      was comparable to that of the reference system and was not reduced when the EEG
      electrodes had high and unbalanced impedances. A common practice with many
      scientific instruments, measurement of EEG device DA provides an independent and
      quantitative assessment of device performance.

PMID- 24727467
TI  - Evaluation of health-care utilization in patients with Dravet syndrome and on
      adjunctive treatment with stiripentol and clobazam.
AB  - Dravet syndrome (DS) is a rare, severe childhood epilepsy syndrome that imposes a
      substantial burden on patients and their caregivers. This study evaluated health
      care utilization over a 2-year period in patients with DS at an outpatient clinic
      of a German epilepsy center. Data on the course of epilepsy, anticonvulsant
      treatment, and direct costs were recorded using the electronic seizure diary
      Epivista and patients' files. We enrolled 13 patients with DS (6 females, mean
      age: 12.3+/-7.5 years) between 2007 and 2010 and evaluated them during a 1-year
      baseline. All patients had drug-resistant epilepsy and their seizures failed to
      improve with a mean number of 6.7+/-3.4 anticonvulsants. They had an overall mean
      seizure frequency of 102.1 seizures per year (median: 31, range: 3-538) with 43.2
      GTCSs per year (median: 14, range: 0-228). We estimated the annual total direct
      costs at ?6506+/-3974 (range: ?1174-11,783) per patient with hospitalization
      (68.9% of total direct costs) as the major cost factor ahead of costs for
      anticonvulsants (24.0%). For the 1-year follow-up period, less severely affected
      patients were continued on conventional anticonvulsants (n=4) or switched to
      adjunctive treatment with stiripentol and clobazam (n=9). In the latter group,
      six patients (67%) were long-term responders, with between 25% and 100% seizure
      reduction with respect to either GTCSs or the overall seizure frequency. This
      reduction in seizure frequency was associated with a shift in the distribution of
      cost components towards higher medication costs and decreased hospitalization
      costs. The total direct costs increased by 42.7%, mainly due to the newly
      introduced stiripentol, with an annual cost of ?6610. This study showed that
      direct costs of patients with DS were above the average European costs of drug
      resistant epilepsy in children. Treatment with new anticonvulsants resulted in
      reduction of seizures and inpatient admissions.

PMID- 24727468
TI  - Treatment of dyslipidemia and cardiovascular outcomes: the journey so far--is
      this the end for statins?
AB  - Dyslipidemia is common and is associated with the highest population-attributable
      risk for cardiovascular disease. Of various cardiovascular preventive therapies,
      the evidence from randomized controlled trials supporting the importance of
      aggressive lipid lowering is the most robust, particularly for statins. Despite
      the use of proven therapies, cardiovascular disease event rates remain relatively
      high, underpinning the development of novel therapies. In addition to testing new
      drugs to reduce low-density-lipoprotein cholesterol, there has been a major focus
      on treatments that can favorably influence high-density-lipoprotein cholesterol
      and triglyceride levels. This review provides an overview of the important
      relationship between lipids and cardiovascular disease, the lipid-modifying
      therapeutic approaches to reducing cardiovascular disease, new guidelines and
      recommendations, and the challenges ahead for the treatment of dyslipidemia,
      particularly whether statins will remain at the forefront of recommended
      therapies.

PMID- 24727469
TI  - An overview of the new frontiers in the treatment of atherogenic dyslipidemias.
AB  - Cardiovascular diseases (CVDs) are the leading cause of morbidity/mortality
      worldwide. Dyslipidemia is a major risk factor for premature atherosclerosis and
      CVD. Lowering low-density-lipoprotein cholesterol (LDL-C) levels is well
      established as an intervention for the reduction of CVDs. Statins are the first
      line drugs for treatment of dyslipidemia, but they do not address all CVD risk.
      Development of novel therapies is ongoing and includes the following: (i)
      reduction of LDL-C concentrations using antibodies to proprotein convertase
      subtilisin/kexin-9, antisense oligonucleotide inhibitors of apolipoprotein B
      production, microsomal transfer protein (MTP) inhibitors, and acyl-coenzyme A
      cholesterol acyl transferase inhibitors; (ii) reduction in levels of triglyceride
      rich lipoproteins with omega-3 fatty acids, MTP inhibitors, and diacylglycerol
      acyl transferase-1 inhibitors; and (iii) increase of high-density-lipoprotein
      (HDL) cholesterol levels, HDL particle numbers, and/or HDL functionality using
      cholesteryl ester transfer protein inhibitors, HDL-derived agents, apolipoprotein
      AI mimetic peptides, and microRNAs. Large prospective outcome trials of several
      of these emerging therapies are under way, and thrilling progress in the field of
      lipid management is anticipated. 

PMID- 24727470
TI  - A current approach to statin intolerance.
AB  - Statins are the first-line pharmacotherapy for cholesterol reduction. Use of
      these drugs in large randomized clinical trials has consistently shown
      significant reductions in major vascular events, including death, myocardial
      infarction, stroke, and coronary revascularization. The updated guidelines for
      the treatment of high blood cholesterol from the American College of
      Cardiology/American Heart Association (ACC/AHA), will lead to an increase in the
      number of patients taking statins. Hence, the number of cases of statin
      intolerance may subsequently increase, emphasizing the need to understand and
      treat this important problem. 

PMID- 24727471
TI  - LMTK2-mediated phosphorylation regulates CFTR endocytosis in human airway
      epithelial cells.
AB  - Cystic fibrosis transmembrane conductance regulator (CFTR) is a Cl(-)-selective
      ion channel expressed in fluid-transporting epithelia. Lemur tyrosine kinase 2
      (LMTK2) is a transmembrane protein with serine and threonine but not tyrosine
      kinase activity. Previous work identified CFTR as an in vitro substrate of LMTK2,
      suggesting a functional link. Here we demonstrate that LMTK2 co
      immunoprecipitates with CFTR and phosphorylates CFTR-Ser(737) in human airway
      epithelial cells. LMTK2 knockdown or expression of inactive LMTK2 kinase domain
      increases cell surface density of CFTR by attenuating its endocytosis in human
      airway epithelial cells. Moreover, LMTK2 knockdown increases Cl(-) secretion
      mediated by the wild-type and rescued DeltaF508-CFTR. Compared with the wild-type
      CFTR, the phosphorylation-deficient mutant CFTR-S737A shows increased cell
      surface density and decreased endocytosis. These results demonstrate a novel
      mechanism of the phospho-dependent inhibitory effect of CFTR-Ser(737) mediated by
      LMTK2 via endocytosis and inhibition of the cell surface density of CFTR Cl(-)
      channels. These data indicate that targeting LMTK2 may increase the cell surface
      density of CFTR Cl(-) channels and improve stability of pharmacologically rescued
      DeltaF508-CFTR in patients with cystic fibrosis. 

PMID- 24727472
TI  - Functional significance of K+ channel beta-subunit KCNE3 in auditory neurons.
AB  - The KCNE3 beta-subunit interacts with and regulates the voltage-dependent gating,
      kinetics, and pharmacology of a variety of Kv channels in neurons. Because a
      single neuron may express multiple KCNE3 partners, it is impossible to predict
      the overall functional relevance of the single transmembrane domain peptide on
      the pore-forming K(+) channel subunits with which it associates. In the inner
      ear, the role of KCNE3 is undefined, despite its association with Meniere disease
      and tinnitus. To gain insights on the functional significance of KCNE3 in
      auditory neurons, we examined the properties of spiral ganglion neurons (SGNs) in
      Kcne3 null mutant neurons relative to their age-matched controls. We demonstrate
      that null deletion of Kcne3 abolishes characteristic wide variations in the
      resting membrane potentials of SGNs and yields age-dependent alterations in
      action potential and firing properties of neurons along the contour of the
      cochlear axis, in comparison with age-matched wild-type neurons. The properties
      of basal SGNs were markedly altered in Kcne3(-/-) mice compared with the wild
      type controls; these include reduced action potential latency, amplitude, and
      increased firing frequency. Analyses of the underlying conductance demonstrate
      that null mutation of Kcne3 results in enhanced outward K(+) currents, which is
      sufficient to explain the ensuing membrane potential changes. Additionally, we
      have demonstrated that KCNE3 may regulate the activity of Kv4.2 channels in SGNs.
      Finally, there were developmentally mediated compensatory changes that occurred
      such that, by 8 weeks after birth, the electrical properties of the null mutant
      neurons were virtually indistinguishable from the wild-type neurons, suggesting
      that ion channel remodeling in auditory neurons progresses beyond hearing onset. 

PMID- 24727473
TI  - Multiple glycosaminoglycan-binding epitopes of monocyte chemoattractant protein
      3/CCL7 enable it to function as a non-oligomerizing chemokine.
AB  - The interaction of chemokines with glycosaminoglycans (GAGs) facilitates the
      formation of localized chemokine gradients that provide directional signals for
      migrating cells. In this study, we set out to understand the structural basis and
      impact of the differing oligomerization propensities of the chemokines monocyte
      chemoattractant protein (MCP)-1/CCL2 and MCP-3/CCL7 on their ability to bind
      GAGs. These chemokines provide a unique comparison set because CCL2 oligomerizes
      and oligomerization is required for its full in vivo activity, whereas CCL7
      functions as a monomer. To identify the GAG-binding determinants of CCL7, an
      unbiased hydroxyl radical footprinting approach was employed, followed by a
      focused mutagenesis study. Compared with the size of the previously defined GAG
      binding epitope of CCL2, CCL7 has a larger binding site, consisting of multiple
      epitopes distributed along its surface. Furthermore, surface plasmon resonance
      (SPR) studies indicate that CCL7 is able to bind GAGs with an affinity similar to
      CCL2 but higher than the non-oligomerizing variant, CCL2(P8A), suggesting that,
      in contrast to CCL2, the large cluster of GAG-binding residues in CCL7 renders
      oligomerization unnecessary for high affinity binding. However, the affinity of
      CCL7 is more sensitive than CCL2 to the density of heparan sulfate on the SPR
      surfaces; this is likely due to the inability of CCL7 to oligomerize because
      CCL2(P8A) also binds significantly less tightly to low than high density heparan
      sulfate surfaces compared with CCL2. Together, the data suggest that CCL7 and
      CCL2 are non-redundant chemokines and that GAG chain density may provide a
      mechanism for regulating the accumulation of chemokines on cell surfaces. 

PMID- 24727474
TI  - A method for activation of endogenous acid-sensing ion channel 1a (ASIC1a) in the
      nervous system with high spatial and temporal precision.
AB  - Protons activate acid-sensing ion channel 1a (ASIC1a) in the central nervous
      system (CNS) although the impact of such activation on brain outputs remains
      elusive. Progress elucidating the functional roles of ASIC1a in the CNS has been
      hindered by technical difficulties of achieving acidification with spatial and
      temporal precision. We have implemented a method to control optically the opening
      of ASIC1a in brain slices and also in awake animals. The light-driven H(+) pump
      ArchT was expressed in astrocytes of mouse cortex by injection of adenoviral
      vectors containing a strong and astrocyte-specific promoter. Illumination with
      amber light acidified the surrounding interstitium and led to activation of
      endogenous ASIC1a channels and firing of action potentials in neurons localized
      in close proximity to ArchT-expressing astrocytes. We conclude that this
      optogenetic method offers a minimally invasive approach that enables examining
      the biological consequences of ASIC1a currents in any structure of the CNS and in
      the modulation of animal behaviors. 

PMID- 24727475
TI  - Endothelial dysfunction in tristetraprolin-deficient mice is not caused by
      enhanced tumor necrosis factor-alpha expression.
AB  - Cardiovascular events are important co-morbidities in patients with chronic
      inflammatory diseases like rheumatoid arthritis. Tristetraprolin (TTP) regulates
      pro-inflammatory processes through mRNA destabilization and therefore TTP
      deficient mice (TTP(-/-) mice) develop a chronic inflammation resembling human
      rheumatoid arthritis. We used this mouse model to evaluate molecular signaling
      pathways contributing to the enhanced atherosclerotic risk in chronic
      inflammatory diseases. In the aorta of TTP(-/-) mice we observed elevated mRNA
      expression of known TTP targets like tumor necrosis factor-alpha (TNF-alpha) and
      macrophage inflammatory protein-1alpha, as well as of other pro-atherosclerotic
      mediators, like Calgranulin A, Cathepsin S, and Osteopontin. Independent of
      cholesterol levels TTP(-/-) mice showed a significant reduction of acetylcholine
      induced, nitric oxide-mediated vasorelaxation. The endothelial dysfunction in
      TTP(-/-) mice was associated with increased levels of reactive oxygen and
      nitrogen species (RONS), indicating an enhanced nitric oxide inactivation by RONS
      in the TTP(-/-) animals. The altered RONS generation correlates with increased
      expression of NADPH oxidase 2 (Nox2) resulting from enhanced Nox2 mRNA stability.
      Although TNF-alpha is believed to be a central mediator of inflammation-driven
      atherosclerosis, genetic inactivation of TNF-alpha neither improved endothelial
      function nor normalized Nox2 expression or RONS production in TTP(-/-) animals.
      Systemic inflammation caused by TTP deficiency leads to endothelial dysfunction.
      This process is independent of cholesterol and not mediated by TNF-alpha solely.
      Thus, other mediators, which need to be identified, contribute to enhanced
      cardiovascular risk in chronic inflammatory diseases. 

PMID- 24727476
TI  - Two dipolar alpha-helices within hormone-encoding regions of proglucagon are
      sorting signals to the regulated secretory pathway.
AB  - Proglucagon is expressed in pancreatic alpha cells, intestinal L cells, and some
      hypothalamic and brainstem neurons. Tissue-specific processing of proglucagon
      yields three major peptide hormones as follows: glucagon in the alpha cells and
      glucagon-like peptides (GLP)-1 and -2 in the L cells and neurons. Efficient
      sorting and packaging into the secretory granules of the regulated secretory
      pathway in each cell type are required for nutrient-regulated secretion of these
      proglucagon-derived peptides. Our previous work suggested that proglucagon is
      directed into granules by intrinsic sorting signals after initial processing to
      glicentin and major proglucagon fragment (McGirr, R., Guizzetti, L., and
      Dhanvantari, S. (2013) J. Endocrinol. 217, 229-240), leading to the hypothesis
      that sorting signals may be present in multiple domains. In the present study, we
      show that the alpha-helices within glucagon and GLP-1, but not GLP-2, act as
      sorting signals by efficiently directing a heterologous secretory protein to the
      regulated secretory pathway. Biophysical characterization of these peptides
      revealed that glucagon and GLP-1 each encode a nonamphipathic, dipolar alpha
      helix, whereas the helix in GLP-2 is not dipolar. Surprisingly, glicentin and
      major proglucagon fragment were sorted with different efficiencies, thus
      providing evidence that proglucagon is first sorted to granules prior to
      processing. In contrast to many other prohormones in which sorting is directed by
      ordered prodomains, the sorting determinants of proglucagon lie within the
      ordered hormone domains of glucagon and GLP-1, illustrating that each prohormone
      has its own sorting "signature." 

PMID- 24727478
TI  - Solution NMR structure of the DNA-binding domain from Scml2 (sex comb on midleg
      like 2).
AB  - Scml2 is a member of the Polycomb group of proteins involved in epigenetic gene
      silencing. Human Scml2 is a part of a multisubunit protein complex, PRC1
      (Polycomb repressive complex 1), which is responsible for maintenance of gene
      repression, prevention of chromatin remodeling, preservation of the "stemness" of
      the cell, and cell differentiation. Although the majority of PRC1 subunits have
      been recently characterized, the structure of Scml2 and its role in PRC1-mediated
      gene silencing remain unknown. In this work a conserved protein domain within
      human Scml2 has been identified, and its structure was determined by solution NMR
      spectroscopy. This module was named Scm-like embedded domain, or SLED.
      Evolutionarily, the SLED domain emerges in the first multicellular organisms,
      consistent with the role of Scml2 in cell differentiation. Furthermore, it is
      exclusively found within the Scm-like family of proteins, often accompanied by
      malignant brain tumor domain (MBT) and sterile alpha motif (SAM) domains. The
      domain adopts a novel alpha/beta fold with no structural analogues found in the
      Protein Data Bank (PDB). The ability of the SLED to bind double-stranded DNA was
      also examined, and the isolated domain was shown to interact with DNA in a
      sequence-specific manner. Because PRC1 complexes localize to the promoters of a
      specific subset of developmental genes in vivo, the SLED domain of Scml2 may
      provide an important link connecting the PRC1 complexes to their target genes. 

PMID- 24727479
TI  - Patient and public involvement in research and the Cancer Experiences
      Collaborative: benefits and challenges.
AB  - AIMS AND OBJECTIVES: The involvement of patients in the design and conduct of
      research is increasingly promoted by policy and research bodies. The experiences
      of individuals who become involved in research in this way are not well
      understood. This study aims to describe the experiences of people's participation
      in patient and public involvement (PPI) in supportive and palliative care
      research, specifically with respect to the benefits and challenges of
      participation for the individuals and the broader research support structures.
      METHODS: In this qualitative exploratory study, semistructured interviews were
      undertaken with individuals who had a cancer diagnosis and were involved in a
      supportive and palliative care research collaborative over a period of 6 years.
      Recruitment was through the host university organisations involved in the
      research collaborative. A thematic analysis was undertaken to identify
      commonalities and differences across their experiences. FINDINGS: The eight
      participants in the study were highly motivated and undertook PPI in research
      alongside other voluntary activities. They identified a number of research and
      personal benefits: bringing a lay perspective into research, making a difference
      and personal gains. Personal gains concerned support, new knowledge and skills
      and greater confidence. The challenges to participation that were identified
      included the emotional and practical nature of the work, issues of language and
      identifying the difference made. CONCLUSIONS: Involvement in supportive and
      palliative care research is valued by people with a cancer diagnosis, but there
      are ongoing issues of emotional support and good communication through the use of
      appropriate language in documentation.

PMID- 24727477
TI  - Mediator, TATA-binding protein, and RNA polymerase II contribute to low histone
      occupancy at active gene promoters in yeast.
AB  - Transcription by RNA polymerase II (Pol II) in eukaryotes requires the Mediator
      complex, and often involves chromatin remodeling and histone eviction at active
      promoters. Here we address the role of Mediator in recruitment of the Swi/Snf
      chromatin remodeling complex and its role, along with components of the
      preinitiation complex (PIC), in histone eviction at inducible and constitutively
      active promoters in the budding yeast Saccharomyces cerevisiae. We show that
      recruitment of the Swi/Snf chromatin remodeling complex to the induced CHA1
      promoter, as well as its association with several constitutively active
      promoters, depends on the Mediator complex but is independent of Mediator at the
      induced MET2 and MET6 genes. Although transcriptional activation and histone
      eviction at CHA1 depends on Swi/Snf, Swi/Snf recruitment is not sufficient for
      histone eviction at the induced CHA1 promoter. Loss of Swi/Snf activity does not
      affect histone occupancy of several constitutively active promoters; in contrast,
      higher histone occupancy is seen at these promoters in Mediator and PIC component
      mutants. We propose that an initial activator-dependent, nucleosome remodeling
      step allows PIC components to outcompete histones for occupancy of promoter
      sequences. We also observe reduced promoter association of Mediator and TATA
      binding protein in a Pol II (rpb1-1) mutant, indicating mutually cooperative
      binding of these components of the transcription machinery and indicating that it
      is the PIC as a whole whose binding results in stable histone eviction. 

PMID- 24727480
TI  - Exploring the associations between drug side-effects and therapeutic indications.
AB  - Drug therapeutic indications and side-effects are both measurable patient
      phenotype changes in response to the treatment. Inferring potential drug
      therapeutic indications and identifying clinically interesting drug side-effects
      are both important and challenging tasks. Previous studies have utilized either
      chemical structures or protein targets to predict indications and side-effects.
      In this study, we compared drug therapeutic indication prediction using various
      information including chemical structures, protein targets and side-effects. We
      also compared drug side-effect prediction with various information sources
      including chemical structures, protein targets and therapeutic indication.
      Prediction performance based on 10-fold cross-validation demonstrates that drug
      side-effects and therapeutic indications are the most predictive information
      source for each other. In addition, we extracted 6706 statistically significant
      indication-side-effect associations from all known drug-disease and drug-side
      effect relationships. We further developed a novel user interface that allows the
      user to interactively explore these associations in the form of a dynamic
      bipartitie graph. Many relationship pairs provide explicit repositioning
      hypotheses (e.g., drugs causing postural hypotension are potential candidates for
      hypertension) and clear adverse-reaction watch lists (e.g., drugs for heart
      failure possibly cause impotence). All data sets and highly correlated disease
      side-effect relationships are available at
      http://astro.temple.edu/~tua87106/druganalysis.html. 

PMID- 24727481
TI  - Identifying and mitigating biases in EHR laboratory tests.
AB  - Electronic health record (EHR) data show promise for deriving new ways of
      modeling human disease states. Although EHR researchers often use numerical
      values of laboratory tests as features in disease models, a great deal of
      information is contained in the context within which a laboratory test is taken.
      For example, the same numerical value of a creatinine test has different
      interpretation for a chronic kidney disease patient and a patient with acute
      kidney injury. We study whether EHR research studies are subject to biased
      results and interpretations if laboratory measurements taken in different
      contexts are not explicitly separated. We show that the context of a laboratory
      test measurement can often be captured by the way the test is measured through
      time. We perform three tasks to study the properties of these temporal
      measurement patterns. In the first task, we confirm that laboratory test
      measurement patterns provide additional information to the stand-alone numerical
      value. The second task identifies three measurement pattern motifs across a set
      of 70 laboratory tests performed for over 14,000 patients. Of these, one motif
      exhibits properties that can lead to biased research results. In the third task,
      we demonstrate the potential for biased results on a specific example. We conduct
      an association study of lipase test values to acute pancreatitis. We observe a
      diluted signal when using only a lipase value threshold, whereas the full
      association is recovered when properly accounting for lipase measurements in
      different contexts (leveraging the lipase measurement patterns to separate the
      contexts). Aggregating EHR data without separating distinct laboratory test
      measurement patterns can intermix patients with different diseases, leading to
      the confounding of signals in large-scale EHR analyses. This paper presents a
      methodology for leveraging measurement frequency to identify and reduce
      laboratory test biases. 

PMID- 24727482
TI  - Review of Dscam-mediated immunity in shrimp and other arthropods.
AB  - Although true adaptive immunity is only found in vertebrates, there is increasing
      evidence that shrimp and other arthropods exhibit immune specificity and immune
      memory. The invertebrate immune response is now called "innate immunity with
      specificity" or "immune priming", and its underlying mechanisms are still
      unclear. However, while vertebrate antibodies have no invertebrate homolog, the
      Down syndrome cell adhesion molecule (Dscam), which is a hypervariable protein
      created by alternative splicing, can function as a pathogen-specific recognizing
      molecule in arthropods. Here we review our current understanding of the Dscam
      mediated immune responses in arthropods, especially in shrimp, and show that
      Dscam may be involved in both general innate immunity and the pathogen-specific
      immune response. 

PMID- 24727485
TI  - Hardcore adolescent smokers? An examination of the hardening hypothesis by using
      survey data from two Norwegian samples collected eight years apart.
AB  - INTRODUCTION: The hardening hypothesis states that with the declining prevalence
      and growing social disapproval of smoking, remaining smokers are more unwilling
      and unable to quit as well as increasingly characterized by low socioeconomic
      status and psychiatric comorbidity. However, few studies have examined whether
      such characteristics do in fact change in tandem with substantially decreased
      smoking prevalence. METHODS: Two nationwide population-based surveys of 16- to 17
      year-old Norwegian adolescents were conducted according to identical procedures
      in 2002 and 2010. In 2002, 3,438 students participated while 2,813 did so in
      2010, yielding response rates of 91.0% and 83.2%, respectively. Data on smoking
      behavior and a variety of psychosocial variables were obtained. RESULTS: The
      prevalence of daily smoking dropped from 23.7% in 2002 to 7.0% in 2010. The
      association between smoking and parental characteristics, adjustment to school,
      and social integration also shifted, indicating smokers to be more socially
      disadvantaged in 2010 than 2002. However, no changes in the relationship between
      smoking and mental health or use of substances such as alcohol and cannabis were
      found, nor did the number of cigarettes smoked by daily smokers differ between
      2002 and 2010. CONCLUSIONS: The results support the hardening hypothesis, as
      smokers became increasingly socially disadvantaged with decreasing smoking
      prevalence. However, despite reduced prevalence of smoking and growing
      stigmatization, neither greater psychological distress nor increased substance
      use among adolescent daily smokers was observed.

PMID- 24727483
TI  - Smoking cessation outcomes among sexual and gender minority and nonminority
      smokers in extended smoking treatments.
AB  - INTRODUCTION: Sexual and gender minority individuals (i.e., lesbian, gay,
      bisexual, and transgender [LGBT]) have a higher smoking prevalence than
      nonminority individuals. There is limited evidence of smoking abstinence success
      in nontailored smoking treatments among LGBT smokers. METHODS: This study is a
      secondary data analysis comparing the efficacy of extended, nontailored
      treatments among sexual and gender minority and nonminority smokers. Data from
      two clinical trials were combined to increase power and generalizability of the
      findings. Trials began with 12 weeks of counseling, nicotine replacement, and
      bupropion, after which participants were randomized to an extended treatment.
      RESULTS: Follow-up occurred at weeks 12, 24, 52, 64, and 104. Of the sample (n =
      777), 17% identified as sexual and gender minority and 83% as nonminority. The
      sample was 75% non-Hispanic White, with 86% completing at least some college, and
      68% were employed. Sexual and gender minorities were younger and indicated a
      greater desire to quit smoking than nonminority smokers. No other differences
      emerged on demographic, smoking, or mood variables. The average Fagerstrom Test
      for Nicotine Dependence score was 4.8, and mean daily cigarettes was 19.8. The
      generalized estimating equations model revealed no significant differences in
      abstinence between sexual and gender minority smokers and nonminority smokers at
      all follow-up assessments. CONCLUSIONS: Sexual and gender minority smokers appear
      as likely to quit or abstain as nonminority smokers in extended, nontailored
      interventions. However, these findings may not generalize to other geographic
      areas, where access to treatment is limited or a higher stigma of sexual
      orientation exists.

PMID- 24727484
TI  - CHRNA5 variant predicts smoking cessation in patients with acute myocardial
      infarction.
AB  - INTRODUCTION: While smoking is a major modifiable risk factor for secondary
      prevention of myocardial infarction (MI), active smoking is common among patients
      hospitalized with acute MI. Recent studies suggest that nicotinic receptor
      variants, and specifically the high-risk CHRNA5 rs16969968 A allele, are
      associated with cessation failure among noncardiac patients. This study
      investigates the association between CHRNA5 rs16969968 and smoking cessation in
      patients hospitalized with acute MI. METHODS: Using data from the TRIUMPH study,
      we ascertained smoking status at the time of index hospitalization for acute MI
      and 1 year after hospitalization. After adjusting for age and sex, we used
      logistic regression to model the association between smoking cessation and CHRNA5
      rs16969968. RESULTS: At index admission, 752 Caucasian subjects were active
      smokers and 699 were former smokers. Among these ever-smokers, the A allele was
      associated with significantly decreased abstinence (45.0% abstinence for A allele
      carriers vs. 51.7% for GG homozygotes; odds ratio [OR] = 0.70, 95% confidence
      interval [CI] = 0.56-0.88, p = .0027). The A allele was also significantly
      associated with decreased abstinence at 1 year (69.1% abstinence for A allele
      carriers vs. 76.0% for GG homozygotes; OR = 0.70, 95% CI = 0.53-0.94, p = .0185).
      CONCLUSIONS: Among patients who have smoked and who are hospitalized with acute
      MI, the high-risk CHRNA5 allele was associated with lower likelihood of quitting
      before hospitalization and significantly less abstinence 1 year after
      hospitalization with MI. The CHRNA5 rs16969968 genotype may therefore identify
      patients who would benefit from aggressive, personalized smoking cessation
      intervention.

PMID- 24727486
TI  - 1-Aminobenzotriazole modulates oral drug pharmacokinetics through cytochrome P450
      inhibition and delay of gastric emptying in rats.
AB  - The simultaneous effects of the cytochrome P450 inhibitor 1-aminobenzotriazole
      (ABT) on inhibition of in vivo metabolism and gastric emptying were evaluated
      with the test compound 7-(3,5-dimethyl-1H-1,2,4-triazol-1-yl)-3-(4-methoxy-2
      methylphenyl)-2,6-dimethylpyrazolo[5,1-b]oxazole(NVS-CRF38), a novel
      corticotropin releasing factor receptor 1 (CRF1) antagonist with low water
      solubility, and the reference compound midazolam with high water solubility in
      rats. Pretreatment of rats with 100 mg/kg oral ABT administered 2 hours before a
      semisolid caloric test meal markedly delayed gastric emptying. ABT increased
      stomach weights by 2-fold; this is likely attributable to a prosecretory effect
      because stomach concentrations of bilirubin were comparable in ABT and control
      groups. ABT administration decreased the initial systemic exposure of orally
      administered NVS-CRF38 and increased Tmax 40-fold, suggesting gastric retention
      and delayed oral absorption. ABT increased the initial systemic exposure of
      midazolam, however for orally (but not subcutaneously) administered midazolam,
      extensive variability in plasma-concentration time profiles was apparent. Careful
      selection of administration routes is recommended for ABT use in vivo, variable
      oral absorption of coadministered compounds can be expected due to a disturbance
      of gastrointestinal transit. 

PMID- 24727487
TI  - Increased colonic bile acid exposure: a relevant factor for symptoms and
      treatment in IBS.
AB  - OBJECTIVE: Bile acids may play a role in the pathogenesis of IBS. We investigated
      the potential effects of bile acids entering the colon and its role in the
      symptom pattern in IBS. DESIGN: We measured 75Se-labelled homocholic acid-taurine
      (75SeHCAT) retention, and serum levels of 7alpha-hydroxy-4-cholesten-3-one (C4)
      and fibroblast growth factor (FGF) 19 in patients with IBS (n=141) and control
      subjects (75SeHCAT n=29; C4 and FGF19 n=435). In patients with IBS stool
      frequency and form, as well as GI symptom severity were registered, and in a
      proportion of patients colonic transit time and rectal sensitivity were measured
      (n=66). An 8-week open-label treatment with colestipol was offered to patients
      with 75SeHCAT <20%, and the effect of treatment was evaluated with IBS severity
      scoring system and adequate relief of IBS symptoms. RESULTS: Compared with
      controls, patients with IBS had lower 75SeHCAT values (p=0.005), higher C4c
      levels (C4 corrected for cholesterol) (p<0.001), but similar FGF19 levels.
      Abnormal 75SeHCAT retention (<10%) was seen in 18% of patients, whereas 23% had
      elevated C4c levels. Patients with IBS with 75SeHCAT retention <10% had more
      frequent stools, accelerated colonic transit time, rectal hyposensitivity, a
      higher body mass index, higher C4c and lower FGF19 levels. Colestipol treatment
      improved IBS symptoms (IBS severity scoring system 220+/-109 vs. 277+/-106;
      p<0.01), and 15/27 patients fulfilled criteria for treatment response (adequate
      relief >=50% of weeks 5-8). CONCLUSIONS: Increased colonic bile acid exposure
      influences bowel habit and colonic transit time in patients with IBS. A high
      response rate to open label treatment with colestipol supports this, but placebo
      controlled studies are warranted.

PMID- 24727488
TI  - Small sum privacy and large sum utility in data publishing.
AB  - While the study of privacy preserving data publishing has drawn a lot of
      interest, some recent work has shown that existing mechanisms do not limit all
      inferences about individuals. This paper is a positive note in response to this
      finding. We point out that not all inference attacks should be countered, in
      contrast to all existing works known to us, and based on this we propose a model
      called SPLU. This model protects sensitive information, by which we refer to
      answers for aggregate queries with small sums, while queries with large sums are
      answered with higher accuracy. Using SPLU, we introduce a sanitization algorithm
      to protect data while maintaining high data utility for queries with large sums.
      Empirical results show that our method behaves as desired. 

PMID- 24727489
TI  - Pyrazole-5-carboxamides, novel inhibitors of receptor for advanced glycation end
      products (RAGE).
AB  - In an effort to develop novel inhibitors of receptor for advanced glycation end
      products (RAGE) for the treatment of Alzheimer's disease, a series of pyrazole-5
      carboxamides were designed, synthesized and biologically evaluated. Analyses of
      the extensive structure-activity relationship (SAR) led us to identify a 4
      fluorophenoxy analog (40) that exhibited improved in vitro RAGE inhibitory
      activity and more favorable aqueous solubility than the parent 2-aminopyrimidine,
      1. Surface plasmon resonance (SPR) and molecular docking study strongly supported
      the RAGE inhibitory activity of pyrazole-5-carboxamides. The brain Abeta-lowering
      effect of 40 is also described. 

PMID- 24727490
TI  - Round window stimulation with the floating mass transducer at constant
      pretension.
AB  - OBJECTIVE: Mechanical stimulation of the round window (RW) of the cochlea is
      successfully done with the Vibrant Soundbridge (Med-El), but clinical outcomes
      show a substantial degree of variability. One source of variability is variation
      in the static force applied by the stimulator to the round window (Maier et al.,
      2013). In this study we investigated other sources of variability by maintaining
      a constant pre-load testing the effect of a coupler device and the interposition
      of soft tissue between the stimulator and the RW. STUDY DESIGN: Experimental.
      METHODS: The stapes footplate displacement produced by stimulation of the round
      window was determined in fresh human temporal bones. The response to sound and
      actuator stimulation was measured with a Laser Doppler Velocimeter at the stapes
      footplate. The RW was stimulated by a Floating Mass Transducer (FMT) with/without
      (1) an additional RW coupler (supplied by the manufacturer), and (2) the
      interposition of TUTOPATCH between the stimulator and the RW, while maintaining a
      pre-load of ~1.96 mN. RESULTS: In 8 temporal bones with normal stapes footplate
      response to sound, we found an average 11.9 dB increase (500 Hz-2 kHz) under
      controlled conditions by using the coupler together with the interposition. The
      increase was statistically significant at 500 Hz (p < 0.01). Additionally, the
      coupler/interposition combination reduced the variability between experiments
      (FMT alone SD = 10.9 dB; FMT with TUTOPATCH & coupler: SD = 3.4 dB @ 500 Hz) and
      increased the repeatability. CONCLUSION: At controlled static force an improved
      output level, inter-subject variability and repeatability were found by using a
      coupler/TUTOPATCH combination in RW stimulation with the FMT. The high
      variability found in clinical experience is not solely due to inter-subject
      variability, but to coupling conditions and can be optimized further.

PMID- 24727491
TI  - Modeling the utility of binaural cues for underwater sound localization.
AB  - The binaural cues used by terrestrial animals for sound localization in azimuth
      may not always suffice for accurate sound localization underwater. The purpose of
      this research was to examine the theoretical limits of interaural timing and
      level differences available underwater using computational and physical models. A
      paired-hydrophone system was used to record sounds transmitted underwater and
      recordings were analyzed using neural networks calibrated to reflect the auditory
      capabilities of terrestrial mammals. Estimates of source direction based on
      temporal differences were most accurate for frequencies between 0.5 and 1.75 kHz,
      with greater resolution toward the midline (2 degrees ), and lower resolution
      toward the periphery (9 degrees ). Level cues also changed systematically with
      source azimuth, even at lower frequencies than expected from theoretical
      calculations, suggesting that binaural mechanical coupling (e.g., through bone
      conduction) might, in principle, facilitate underwater sound localization.
      Overall, the relatively limited ability of the model to estimate source position
      using temporal and level difference cues underwater suggests that animals such as
      whales may use additional cues to accurately localize conspecifics and predators
      at long distances.

PMID- 24727493
TI  - Pioglitazone reduces angiotensin II-induced COX-2 expression through inhibition
      of ROS production and ET-1 transcription in vascular cells from spontaneously
      hypertensive rats.
AB  - Glitazones have anti-inflammatory properties by interfering with the
      transcription of proinflammatory genes, such as cyclooxygenase (COX)-2, and with
      ROS production, which are increased in hypertension. This study analyzed whether
      pioglitazone modulates COX-2 expression in hypertension by interfering with ROS
      and endothelin (ET)-1. In vivo, pioglitazone (2.5 mg.kg(-1).day(-1), 28 days)
      reduced the greater levels of COX-2, pre-pro-ET-1, and NADPH oxidase (NOX)
      expression and activity as well as O2 (.-) production found in aortas from
      spontaneously hypertensive rats (SHRs). ANG II increased COX-2 and pre-pro-ET-1
      levels more in cultured vascular smooth muscle cells from hypertensive rats
      compared with normotensive rats. The ETA receptor antagonist BQ-123 reduced ANG
      II-induced COX-2 expression in SHR cells. ANG II also increased NOX-1 expression,
      NOX activity, and superoxide production in SHR cells; the selective NOX-1
      inhibitor ML-171 and catalase reduced ANG II-induced COX-2 and ET-1
      transcription. ANG II also increased c-Jun transcription and phospho-JNK1/2,
      phospho-c-Jun, and p65 NF-kappaB subunit nuclear protein expression. SP-600125
      and lactacystin, JNK and NF-kappaB inhibitors, respectively, reduced ANG II
      induced ET-1, COX-2, and NOX-1 levels and NOX activity. Pioglitazone reduced the
      effects of ANG II on NOX activity, NOX-1, pre-pro-ET-1, COX-2, and c-Jun mRNA
      levels, JNK activation, and nuclear phospho-c-Jun and p65 expression. In
      conclusion, ROS production and ET-1 are involved in ANG II-induced COX-2
      expression in SHRs, explaining the greater COX-2 expression observed in this
      strain. Furthermore, pioglitazone inhibits ANG II-induced COX-2 expression likely
      by interfering with NF-kappaB and activator protein-1 proinflammatory pathways
      and downregulating ROS production and ET-1 transcription, thus contributing to
      the anti-inflammatory properties of glitazones. 

PMID- 24727492
TI  - Chronic inhibition of phosphodiesterase 5 with tadalafil attenuates mitochondrial
      dysfunction in type 2 diabetic hearts: potential role of NO/SIRT1/PGC-1alpha
      signaling.
AB  - Enhanced nitric oxide (NO) production is known to activate silent information
      regulator 1 (SIRT1), which is a histone deacetylase that regulates PGC-1alpha, a
      regulator of mitochondrial biogenesis and coactivator of transcription factors
      impacting energy homeostasis. Since phosphodiesterase-5 inhibitors potentiate NO
      signaling, we hypothesized that chronic treatment with phosphodiesterase-5
      inhibitor tadalafil would activate SIRT1-PGC-1alpha signaling and protect against
      metabolic stress-induced mitochondrial dysfunction in diabetic hearts. Diabetic
      db/db mice (n = 32/group; 40 wk old) were randomized to receive DMSO (10%, 0.2 ml
      ip) or tadalafil (1 mg/kg ip in 10% DMSO) for 8 wk. Wild-type C57BL mice served
      as nondiabetic controls. The hearts were excised and homogenized to study SIRT1
      activity and downstream protein targets. Mitochondrial function was determined by
      measuring oxidative phosphorylation (OXPHOS), and reactive oxygen species
      generation was studied in isolated mitochondria. Tadalafil-treated diabetic mice
      demonstrated significantly improved left ventricular function, which is
      associated with increased cardiac SIRT1 activity. Tadalafil also enhanced plasma
      NO oxidation levels, myocardial SIRT1, PGC-1alpha expression, and phosphorylation
      of eNOS, Akt, and AMPK in the diabetic hearts. OXPHOS with the complex I
      substrate glutamate was decreased by 50% in diabetic hearts compared with the
      nondiabetic controls. Tadalafil protected OXPHOS with an improved glutamate state
      3 respiration rates. The increased reactive oxygen species production from
      complex I was significantly decreased by tadalafil treatment. In conclusion,
      chronic treatment with tadalafil activates NO-induced SIRT1-PGC-1alpha signaling
      and attenuates mitochondrial dysfunction in type 2 diabetic hearts. 

PMID- 24727494
TI  - A novel adipocytokine, omentin, inhibits platelet-derived growth factor-BB
      induced vascular smooth muscle cell migration through antioxidative mechanism.
AB  - Omentin is a novel adipocytokine expressed in visceral adipose tissue. Secretion
      and blood concentration of omentin decrease in the obese subjects. We previously
      demonstrated that omentin is anti-inflammatory in vascular smooth muscle cells
      (SMCs). While vascular remodeling via migration of SMCs is also important for
      hypertension development, it remains to be clarified whether omentin affects this
      process. Here we examined whether omentin controls SMC migration. Omentin (300
      ng/ml, 2 h) significantly inhibited platelet-derived growth factor (PDGF)-BB (10
      ng/ml, 6 h)-induced migration of rat mesenteric arterial SMCs, as determined by
      Boyden chamber assay. Omentin (300 ng/ml, 2 h) significantly inhibited PDGF-BB
      (10 ng/ml, 30 min)-induced phosphorylation of p38 and heat shock protein (HSP)
      27. Omentin (300 ng/ml, 2 h) significantly inhibited PDGF-BB (10 ng/ml, 30 min)
      induced NADPH oxidase (NOX) activation as determined by lucigenin assay. Omentin
      (300 ng/ml, 24 h) significantly inhibited fetal bovine serum (5%, 4 days)-induced
      SMC outgrowth from rat isolated mesenteric artery. In vivo, omentin significantly
      inhibited carotid intimal hyperplasia in mouse ligation model. In summary, we for
      the first time demonstrate that omentin prevents PDGF-BB-induced SMC migration by
      preventing NOX/O2(-)/p38/HSP27 pathways, which might be at least partly
      responsible for the preventive effects on neointimal hyperplasia. Our data
      suggest that omentin may be protective against hypertension development by
      inhibiting vascular structural remodeling.

PMID- 24727495
TI  - Endostatin and kidney fibrosis in aging: a case for antagonistic pleiotropy?
AB  - A recurring theme of a host of gerontologic studies conducted in either
      experimental animals or in humans is related to documenting the functional
      decline with age. We hypothesize that elevated circulating levels of a powerful
      antiangiogenic peptide, endostatin, represent one of the potent systemic causes
      for multiorgan microvascular rarefaction and functional decline due to fibrosis.
      It is possible that during the life span of an organism there is an accumulation
      of dormant transformed cells producing antiangiogenic substances (endostatin)
      that maintain the dormancy of such scattered malignant cells. The proof of this
      postulate cannot be obtained by physically documenting these scattered cells, and
      it rests exclusively on the detection of sequelae of shifted pro- and
      antiangiogenic balance toward the latter. Here we compared circulating levels of
      endostatin in young and aging mice of two different strains and showed that
      endostatin levels are elevated in the latter. Renal expression of endostatin
      increased ~5.6-fold in aging animals. This was associated with microvascular
      rarefaction and progressive tubulointerstitial fibrosis. In parallel, the levels
      of sirtuins 1 and 3 were significantly suppressed in aging mice in conjunction
      with the expression of markers of senescence. Treating young mice with endostatin
      for 28 days showed delayed recovery of circulation after femoral artery ligation
      and reduced patency of renal microvasculature but no fibrosis. In conclusion, the
      findings are consistent with the hypothesis on elevation of endostatin levels and
      parallel microvascular rarefaction and induction of renal fibrosis in aging mice.

PMID- 24727496
TI  - ATP-binding cassette transporter Abcg2 lineage contributes to the cardiac
      vasculature after oxidative stress.
AB  - Due to their specialized location, stem and progenitor cells are often exposed to
      oxidative stress. Although ATP-binding cassette transporter subfamily G member 2
      (Abcg2)-expressing cells have been implicated in cardiac protective mechanisms
      involving oxidative stress, there remains a lack of understanding regarding the
      behavior of cardiac Abcg2-expressing cells when exposed to ROS. The aim of the
      present study was to characterize the response of the cardiac Abcg2 lineage to
      oxidative stress. In vitro analysis demonstrated that the antioxidant program
      regulated by Abcg2 is dependent on a functional transporter. Delivery of paraquat
      dichloride (PQ), a systemic oxidative stress-inducing agent, to mice confirmed
      that Abcg2 provides a survival benefit. When exposed to PQ, reporter mice showed
      an increase in the Abcg2 lineage. Transcriptional and immunohistochemical
      analysis of Abcg2 lineage-positive cells revealed an enhanced vascular commitment
      after stress. Finally, preconditioning with PQ demonstrated a reduction in scar
      size and an increase in angiogenesis after permanent left coronary artery
      ligation. In conclusion, the data suggest that Abcg2 plays a cytoprotective role
      in response to in vivo oxidative stress. The contribution of the Abcg2 lineage to
      the vasculature in the heart is increased after PQ delivery.

PMID- 24727497
TI  - Molecular and structural characterization of dissolved organic matter during and
      post cyanobacterial bloom in Taihu by combination of NMR spectroscopy and FTICR
      mass spectrometry.
AB  - Seasonal molecular changes in dissolved organic matter (DOM) isolated from Tai
      Lake (Taihu) both during (June) and following (November) an algal bloom event in
      2007 were characterized by nuclear magnetic resonance spectroscopy (NMR) and
      Fourier transform ion cyclotron resonance (FTICR) mass spectrometry. Considerable
      biosignatures were present in summer DOM, yet with a near absence of algal
      extract compounds. Extensive molecular alteration resulting from multistep and
      massively parallel biotic and subordinated abiotic transformations of algal
      biomass to DOM included loss and synthesis of carbohydrates, fundamental changes
      of aromatic compounds and progressive formation of carboxyl-rich alicyclic
      compounds (CRAM). The DOM transformation from summer to fall resulted in smaller
      molecules, increased abundance of CHNO continuous molecular series and overall
      molecular diversity. Analysis of MS-derived compositional networks placed summer
      DOM in-between the algal extract and fall DOM. Metabolic pathway annotation by
      means of high-resolution mass analysis provided a wide range of pathways
      associated with secondary metabolites in DOM and more basic ones like
      carbohydrate metabolism characteristic of algal extract compounds. Overall, the
      time-dependent molecular signature of Taihu DOM was likely dominated by microbial
      metabolism rather than abiotic chemical transformations. Results from this study
      indicate that high-resolution organic structural spectroscopy resolves meaningful
      structural detail out of complex environmental mixtures and has the potential to
      contribute significantly to future functional biodiversity studies. 

PMID- 24727498
TI  - Efficient immobilization of mushroom tyrosinase utilizing whole cells from
      Agaricus bisporus and its application for degradation of bisphenol A.
AB  - A simple and efficient procedure for preparation and immobilization of tyrosinase
      enzyme was developed utilizing whole cells from the edible mushroom Agaricus
      bisporus, without the need for enzyme purification. Tyrosinase activity in the
      cell preparation remained constant during storage at 21  degrees C for at least
      six months. The cells were entrapped in chitosan and alginate matrix capsules and
      characterized with respect to their resulting tyrosinase activity. A modification
      of the alginate with colloidal silica enhanced the activity due to retention of
      both cells and tyrosinase from fractured cells, which otherwise leached from
      matrix capsules. The observed activity was similar to the activity that was
      obtained with immobilized isolated tyrosinase in the same material. Mushroom
      cells in water were susceptible to rapid inactivation, whereas the immobilized
      cells maintained 73% of their initial activity after 30 days of storage in water.
      Application in repeated batch experiments resulted in almost 100% conversion of
      endocrine disrupting bisphenol A (BPA) for 11 days, under stirring conditions,
      and 50-60% conversion after 20 days, without stirring under continuous usage. The
      results represent the longest yet reported application of immobilized tyrosinase
      for degradation of BPA in environmental water samples. 

PMID- 24727499
TI  - A framework for the next generation of risk science.
AB  - OBJECTIVES: In 2011, the U.S. Environmental Protection Agency initiated the
      NexGen project to develop a new paradigm for the next generation of risk science.
      METHODS: The NexGen framework was built on three cornerstones: the availability
      of new data on toxicity pathways made possible by fundamental advances in basic
      biology and toxicological science, the incorporation of a population health
      perspective that recognizes that most adverse health outcomes involve multiple
      determinants, and a renewed focus on new risk assessment methodologies designed
      to better inform risk management decision making. RESULTS: The NexGen framework
      has three phases. Phase I (objectives) focuses on problem formulation and
      scoping, taking into account the risk context and the range of available risk
      management decision-making options. Phase II (risk assessment) seeks to identify
      critical toxicity pathway perturbations using new toxicity testing tools and
      technologies, and to better characterize risks and uncertainties using advanced
      risk assessment methodologies. Phase III (risk management) involves the
      development of evidence-based population health risk management strategies of a
      regulatory, economic, advisory, community-based, or technological nature, using
      sound principles of risk management decision making. CONCLUSIONS: Analysis of a
      series of case study prototypes indicated that many aspects of the NexGen
      framework are already beginning to be adopted in practice.

PMID- 24727500
TI  - Thermal-infrared pedestrian ROI extraction through thermal and motion information
      fusion.
AB  - This paper investigates the robustness of a new thermal-infrared pedestrian
      detection system under different outdoor environmental conditions. In first place
      the algorithm for pedestrian ROI extraction in thermal-infrared video based on
      both thermal and motion information is introduced. Then, the evaluation of the
      proposal is detailed after describing the complete thermal and motion information
      fusion. In this sense, the environment chosen for evaluation is described, and
      the twelve test sequences are specified. For each of the sequences captured from
      a forward-looking infrared FLIR A-320 camera, the paper explains the weather and
      light conditions under which it was captured. The results allow us to draw firm
      conclusions about the conditions under which it can be affirmed that it is
      efficient to use our thermal-infrared proposal to robustly extract human ROIs. 

PMID- 24727501
TI  - An upper-limb power-assist exoskeleton using proportional myoelectric control.
AB  - We developed an upper-limb power-assist exoskeleton actuated by pneumatic
      muscles. The exoskeleton included two metal links: a nylon joint, four size
      adjustable carbon fiber bracers, a potentiometer and two pneumatic muscles. The
      proportional myoelectric control method was proposed to control the exoskeleton
      according to the user's motion intention in real time. With the feature
      extraction procedure and the classification (back-propagation neural network), an
      electromyogram (EMG)-angle model was constructed to be used for pattern
      recognition. Six healthy subjects performed elbow flexion-extension movements
      under four experimental conditions: (1) holding a 1-kg load, wearing the
      exoskeleton, but with no actuation and for different periods (2-s, 4-s and 8-s
      periods); (2) holding a 1-kg load, without wearing the exoskeleton, for a fixed
      period; (3) holding a 1-kg load, wearing the exoskeleton, but with no actuation,
      for a fixed period; (4) holding a 1-kg load, wearing the exoskeleton under
      proportional myoelectric control, for a fixed period. The EMG signals of the
      biceps brachii, the brachioradialis, the triceps brachii and the anconeus and the
      angle of the elbow were collected. The control scheme's reliability and power
      assist effectiveness were evaluated in the experiments. The results indicated
      that the exoskeleton could be controlled by the user's motion intention in real
      time and that it was useful for augmenting arm performance with neurological
      signal control, which could be applied to assist in elbow rehabilitation after
      neurological injury. 

PMID- 24727502
TI  - Optimization of dengue immunoassay by label-free interferometric optical
      detection method.
AB  - In this communication we report a direct immunoassay for detecting dengue virus
      by means of a label-free interferometric optical detection method. We also
      demonstrate how we can optimize this sensing response by adding a blocking step
      able to significantly enhance the optical sensing response. The blocking reagent
      used for this optimization is a dry milk diluted in phosphate buffered saline.
      The recognition curve of dengue virus over the proposed surface sensor
      demonstrates the capacity of this method to be applied in Point of Care
      technology. 

PMID- 24727503
TI  - Immune responses during gestational malaria: a review of the current knowledge
      and future trend of research.
AB  - Women pregnant with their first child are susceptible to severe P. falciparum
      disease from placental malaria because they lack immunity to placenta-specific
      cytoadherence proteins. In subsequent pregnancies, as immunity against placental
      parasites is acquired, there is a reduced risk of adverse effects of malaria on
      the mother and fetus and asymptomatic parasitaemia is common. In the case of
      vivax malaria, with increasing reports of severe cases in Asia and South America,
      the effects of infection by this species during pregnancy remain to be
      elucidated. This review summarized the main aspects involved in the acquisition
      of specific antimalarial immune responses during pregnancy with emphasis in
      research carried out in America and Asia, in order to offer a framework of
      interpretation for studies on pregnant women with malaria which are recently
      being produced in these regions. The authors conclude that (1) Effective humoral
      responses during gestational malaria are mainly directed against variant surface
      antigens codified by genes of the var2Csa family of P. falciparum; (2)
      Acquisition of immunity against these variant antigens depends on the degree and
      intensity of transmission, and the chance increases with age and successive
      pregnancies; (3) Antibody development is guided by specific cellular immune
      responses in cases of placental and maternal infection, and (4) The study of the
      significance of acquisition of specific immunity against both P. falciparum and
      P. vivax in America, should be performed. 

PMID- 24727504
TI  - Sexual and vertical transmission of visceral leishmaniasis.
AB  - Visceral leishmaniasis (VL) is an important zoonosis caused by Leishmania
      infantum, which has in the domestic dog its principal vertebrate host. VL is
      usually transmitted by phlebotomine sand flies, however atypical routes of
      transmission have been described. In this review we discuss the the role of
      sexual and vertical transmissions, and their role in the maintenance of VL in
      canine populations. 

PMID- 24727505
TI  - Comparative evaluation of six phenotypic methods for detecting extended-spectrum
      beta-lactamase-producing Enterobacteriaceae.
AB  - INTRODUCTION: Various conventional phenotypic methods and automated systems have
      been evaluated for extended-spectrum beta-lactamase (ESBL) detection. There is a
      paucity of data comparing these methods using the same clinical isolates in
      eastern and north-eastern parts of India. The present study was designed to
      compare the capacity of six phenotypic methods to detect ESBLs in clinical
      isolates of Enterobacteriaceae. METHODOLOGY: A total of 206 non-duplicate clini
      cal isolates of Enterobacteriaceae, obtained over a period of six months (July to
      December, 2012), were tested by the Vitek 2, double disk synergy tests (30 mm, 20
      mm, and modified method), combined disk test, and ESBL Etest to evaluate their
      ability to detect ESBLs. Minimal inhibitory concentration (MIC) by the agar
      dilution method was used as the reference method. RESULTS: The reference method
      detected ESBLs in 57 (27.7%) isolates. Among the six methods, the combined disk
      test demonstrated an overall agreement of 100% with the MIC. The Vitek 2 showed a
      sensitivity and specificity of 91.8% and 97.24%, respectively, with a positive
      predictive value of 93.33%. The sensitivities of the conventional methods ranged
      from 83% to 94%. The highest sensitivity and specificity were shown by combined
      disk (93.44%) and double disk synergy (100%) techniques, respectively.
      CONCLUSION: In our setting, Vitek 2 showed an acceptable capacity to detect ESBL
      isolates as it improved the turnover time (6 to 8 hours) in comparison to
      conventional phenotypic methods, which took a minimum of 24 hours. However, the
      combined disk test achieved the highest sensitivity.

PMID- 24727506
TI  - Characterization of antibiotic resistance in Listeria spp. isolated from
      slaughterhouse environments, pork and human infections.
AB  - INTRODUCTION: Listeria species are susceptible to most antibiotics. However, over
      the last decade, increasing reports of multidrug-resistant Listeria spp. from
      various sources have prompted public health concerns. The objective of this study
      was to characterize the antibiotic susceptibility of Listeria spp. and the
      genetic mechanisms that confer resistance. METHODOLOGY: Forty-six Listeria spp.
      isolates were studied, and their minimal inhibitory concentrations of antibiotics
      were determined by microdilution using Sensititre standard susceptibility MIC
      plates. The isolates were screened for the presence of gyrA, parC, lde, lsa(A),
      lnu(A), and mprF by PCR, and the amplified genes were sequenced. RESULTS: All
      isolates were susceptible to penicillin, ampicillin, tetracycline, erythromycin,
      and carbapenems. Resistance to clindamycin, daptomycin, and oxacillin was found
      among L. monocytogenes and L. innocua, and all species possessed at least
      intermediate resistance to fluoroquinolones. GyrA, parC, and mprF were detected
      in all isolates; however, mutations were found only in gyrA sequences. A high
      daptomycin MIC, as reported previously, was observed, suggesting an intrinsic
      resistance of Listeria spp. to daptomycin. CONCLUSIONS: These results are
      consistent with reports of emerging resistance in Listeria spp. and emphasize the
      need for further genotypic characterization of antibiotic resistance in this
      genus.

PMID- 24727507
TI  - Antibiotic use and knowledge in the community of Yemen, Saudi Arabia, and
      Uzbekistan.
AB  - INTRODUCTION: Inappropriate use of antibiotics has resulted in a dramatic
      increase of antimicrobial resistance in developing countries. We examined
      knowledge, attitudes, and practices of antibiotic use in three Asian countries.
      METHODOLOGY: A nationwide cross-sectional study of teachers in large cities of
      Yemen, Saudi Arabia, and Uzbekistan was conducted. A random sample of 1,200
      teachers was selected in each country. Data were collected through a
      questionnaire-based survey and then analyzed using descriptive and multivariate
      statistical methods. RESULTS: The prevalence of non-prescription antibiotic use
      ranged from 48% in Saudi Arabia to 78% in Yemen and Uzbekistan. Pharmacies were
      the main source of non-prescribed antibiotics. The most common reasons for
      antibiotic use were cough (40%) and influenza (34%). Forty-nine percent of
      respondents discontinued antibiotics when they felt better. Although awareness of
      the dangers of antibiotic use correlated inversely with self-medication,
      understanding of the appropriate use of antibiotics was limited. CONCLUSIONS: The
      prevalence of antibiotic self-medication in the educated adult population in the
      studied countries was found to be alarmingly high. Effective strategies involving
      regulatory enforcement prohibiting sales of antibiotics without prescription
      should be implemented along with educational interventions for health
      professionals and the public.

PMID- 24727508
TI  - Genetic diversity of TLR2, TLR4, and VDR loci and pulmonary tuberculosis in
      Moroccan patients.
AB  - INTRODUCTION: Toll-like receptors (TLRs) 2, 4, and the vitamin D receptor (VDR)
      are central components of the innate and adaptive immunity against Mycobacterium
      tuberculosis (Mtb). TLR2, TLR4, and VDR polymorphisms were previously associated
      with tuberculosis (TB) and were here investigated as candidates for pulmonary TB
      (PTB) susceptibility in a Moroccan population group. METHODOLOGY: Genomic DNA
      from 343 PTB patients and 203 healthy controls were analyzed for 12 single
      nucleotide polymorphisms (SNPs) located in TLR2, TLR4, and VDR genes using
      polymerase chain reaction-based restriction fragment length polymorphism and
      TaqMan SNP genotyping assays. RESULTS: The TLR2 +597 CT genotype was associated
      with protection against PTB (corrected p [pc] = 0.04; odds ratio (OR) = 0.65; 95%
      confidence interval (CI) = 0.45 - 0.94), and the TLR4 +7263 C allele was
      significantly associated with PTB susceptibility (pc = 0.04; OR = 1.63; CI = 1.06
      - 2.57). The VDR [f,b,a,T] haplotype was found to confer protection (pc <
      0.00001; OR = 0.18; CI = 0.09 - 0.35), while the TLR2 [-16934T,+597C,+1349T]
      haplotype seemed to be at risk (p = 0.03; OR = 1.52; CI = 1.01 - 2.30), but
      statistical significance was not reached. Finally, cross-analysis between
      polymorphisms of the three studied genes revealed significant interaction between
      TLR2 +597 and TLR4 +4434 SNPs towards protection against PTB (pc = 0.036),
      suggesting that the functionally relevant TLR4 +4434 SNP may act synergistically
      with TLR2 SNPs. CONCLUSIONS: TLR2 and TLR4 interaction and a specific VDR
      haplotype influence protection against PTB in Moroccans patients.

PMID- 24727509
TI  - Molecular typing of Staphylococcus aureus collected from a Major Hospital in
      Amman, Jordan.
AB  - INTRODUCTION: Over the past decade methicillin-resistant Staphylococcus aureus
      (MRSA) has been recognized as a major cause of healthcare associated infections.
      Recently, however, epidemiology of this pathogen has changed drastically with the
      emergence of new clones in the community. Efficient epidemiological typing
      methods are essential to monitor and limit the occurrence and spread of epidemic
      clones. METHODOLOGY: A total of sixty S. aureus isolates were collected from the
      Jordan University hospital in Amman-Jordan. All isolates were characterized using
      Staphylococcus protein A (spa) typing and pulsed-field gel electrophoresis
      (PFGE). Samples were tested for their susceptibility patterns against seven
      antimicrobial agents and for their potential to form biofilms. RESULTS: spa
      typing showed that spa type t044 was the most common representing 28% of the
      isolates studied and 38% of the MRSA population. PFGE revealed fourty-six
      pulsotypes among the sixty tested isolates clustering similar spa types together.
      The predominant resistance was detected against levofloxacin, chloramphenicol and
      clindamycin. One MSSA isolate typed as spa t955 showed biofilm formation
      potential through protein deposition.. CONCLUSION: The study results are based on
      one hospital, but the findings of this and other studies conducted in the region
      indicate that there is an urgent need for standardized surveillances combined
      with the application of well-validated typing methods to assess the occurrence of
      MRSA and to control its spread.

PMID- 24727510
TI  - Helicobacter pylori associated with breastfeeding, nutritional status and
      recurrent abdominal pain in healthy Nigerian children.
AB  - INTRODUCTION: There is limited knowledge about the associations of Helicobacter
      pylori (H. pylori) infections in developing countries. This study aimed to
      determine the current prevalence and associations of H. pylori infection with
      breastfeeding practices, nutritional status, and recurrent abdominal pain (RAP)
      in a group of apparently healthy children and adolescents in Lagos, Nigeria.
      METHODOLOGY: This was a prospective hospital-based study conducted at the Lagos
      State University Teaching Hospital that involved 118 children who came to the
      hospital for routine pediatric care. Seroprevalence status of the children was
      determined by measuring immunoglobulin G antibodies against H. pylori using
      enzyme-linked immunosorbent assay (ELISA). RESULTS: Seventy-five (63.6%) children
      were seropositive for H. pylori. The prevalence of H. pylori infection increased
      significantly from 40.4% in children less than five years of age to 85.1% at six
      to ten years of age (chi(2) = 20.9, p < 0.001). H. pylori infection was
      associated with low social class (OR = 3.24; 95% CI = 1.20-8.23, p = 0.016) and
      with RAP (OR = 3.47; 95% CI = 1.55-7.79, p = 0.002), but no association was
      observed with exclusive breastfeeding, duration of breastfeeding, and under
      nutrition. CONCLUSIONS: The prevalence of H. pylori infection is high,
      particularly among children from low socioeconomic backgrounds in Lagos, Nigeria.
      It is associated with RAP. The effect of this infection on children's health
      requires further studies.

PMID- 24727511
TI  - Emergence and clonal dissemination of Salmonella enterica serovar Enteritidis
      causing salmonellosis in Mauritius.
AB  - INTRODUCTION: For decades, Salmonella enterica serovar Enteritidis has been among
      the most prevalent serovars reported worldwide. However, it was rarely
      encountered in Mauritius until 2007; since then the number of non-typhoidal
      Salmonella serogroup O:9 (including serovar Enteritidis) increased. A study was
      conducted to investigate the genetic relatedness between S. Enteritidis isolates
      recovered in Mauritius from food and clinical specimens (stool, blood, and
      exudate). METHODOLOGY: Forty-seven isolates of S. Enteritidis obtained in 2009
      from human stools, blood cultures and exudates, and from food specimens were
      characterized by antimicrobial susceptibility testing and Multiple-Locus Variable
      number tandem repeat Analysis (MLVA). RESULTS: With the exception of a single
      isolate which demonstrated intermediate susceptibility to streptomycin, all
      isolates were pansusceptible to the 14 antimicrobials tested. Thirty seven out of
      the 47 isolates (78.7%) exhibited an indistinguishable MLVA profile which
      included isolates from ready-to-eat food products, chicken, and human clinical
      isolates from stool, blood and exudate. CONCLUSIONS: The presence of highly
      related strains in both humans and raw chicken, and the failure to isolate the
      serovar from other foods, suggests that poultry is the main reservoir of S.
      Enteritidis in Mauritius and that the majority of human cases are associated with
      chicken consumption which originated from one major producer. Stool isolates were
      indistinguishable or closely related to blood and exudate isolates, indicating
      that, besides gastroenteritis, the same strain caused invasive infections.
      Control of S.Enteritidis by poultry breeders would lower the financial burden
      associated with morbidity in humans caused by this organism in Mauritius.

PMID- 24727512
TI  - Identification of the most common pathogenic bacteria in patients with suspected
      sepsis by multiplex PCR.
AB  - INTRODUCTION: Staphylococcus aureus, coagulase-negative staphylococci,
      Enterococcus spp., Enterobacteriaceae, Pseudomonas aeruginosa, and Acinetobacter
      baumanii have been found to be the most prevalent bacteremia-causing bacteria in
      patients with septicemia. Early detection of bloodstream infection (BSI) is
      crucial in the clinical setting. A multiplex PCR method for identification of
      these agents in clinical samples has been developed in parallel by conventional
      microbiological methods. METHODOLOGY: The target genes selected for each of the
      organisms were very specific for designing primers. Design of primers was done
      using Mega4, Allel ID6, Oligo6, and Oligo analyzer software. The test comprises a
      universal PCR from the 16S rDNA gene and multiplex PCR from the rpoB, gyrA, sss,
      and chromosome X (as an internal control). RESULTS: The sensitivity and
      specificity for universal PCR and multiplex PCR in comparison with BC were 83.87%
      and 91.58%, and 74.19% and 91.58%, respectively. The positive predictive value
      (PPV) and the negative predictive value (NPV) for these two PCRs were 76.47% and
      94.57%, and 74.19% and 91.58%, respectively. PCR failed to identify bacteria
      which were found conventionally in only 3.96% and 6.34% of the cases by universal
      and multiplex PCR (mostly bacteria not included in the PCR cassette). In 6.34% of
      the cases, multiplex PCR afforded identification of bacteria, but BC showed no
      bacteria in the sample. CONCLUSIONS: The multiplex PCR approach facilitates the
      detection of bacteremia in blood samples within a few hours. Rapid detection of
      bacteria by multiplex PCR appears to be a valuable tool, allowing earlier
      pathogen-adopted antimicrobial therapy in critically ill patients.

PMID- 24727513
TI  - PCR deduction of invasive and colonizing pneumococcal serotypes from Venezuela: a
      critical appraisal.
AB  - INTRODUCTION: Serotype surveillance of Streptococcus pneumoniae is indispensable
      for evaluating the potential impact of pneumococcal conjugate vaccines.
      Serotyping by the standard Quellung reaction is technically demanding, time
      consuming, and expensive. A simple and economical strategy is multiplex PCR-based
      serotyping. We evaluated the cost effectiveness of a modified serial multiplex
      PCR (mPCR), resolving 24 serotypes in four PCR reactions and optimally targeting
      the most prevalent invasive and colonizing pneumococcal serotypes found in
      Venezuela. METHODOLOGY: A total of 223 pneumococcal isolates, 140 invasive and 83
      carriage isolates, previously serotyped by the Quellung reaction and representing
      the 18 most common serotypes/groups identified in Venezuela, were serotyped with
      the adapted mPCR. RESULTS: The mPCR serotyped 76% of all the strains in the first
      two PCR reactions and 91% after four reactions, correctly identifying 17
      serotypes/groups. An isolate could be serotyped with mPCR in less than 2 minutes
      versus 15 minutes for the Quellung reaction, considerably lowering labor costs. A
      restrictive weakness of mPCR was found for the detection of 19F strains. Most
      Venezuelan 19F strains were not typeable using the mPCR, and two 19F cps serotype
      variants were identified. CONCLUSIONS: The mPCR assay is an accurate, rapid, and
      economical method for the identification of the vast majority of the serotypes
      from Venezuela and can be used in place of the standard Quellung reaction. An
      exception is the identification of serotype 19F. In this setting, most 19F
      strains were not detectable with mPCR, demonstrating a need of serology-based
      quality control for PCR-based serotyping.

PMID- 24727514
TI  - Expression of ompR gene in the acid adaptation and thermal resistance of
      Salmonella Enteritidis SE86.
AB  - INTRODUCTION: The objective of this study was to evaluate the involvement of the
      ompR gene in the acid adaptation and thermal resistance of S. Enteritidis SE86,
      responsible agent of more than 95 % of investigated food-borne diseases,
      throughout the last decade in Southern Brazil. In this study, we constructed a
      mutant strain of S. Enteritidis SE86 (DeltaompR) that was attenuated by a
      knockout technique. The OmpR protein expression was determined in a tagged
      (3XFLAG) strain of S. Enteritidis SE86. METHODOLOGY: The mutant strains were
      cultivated separately in nutrient broth and nutrient broth supplemented with 1%
      glucose (NBG) to induce acid adapted cells. The organisms were exposed to
      different temperature such as 37 oC, 52 oC, and 60oC. The survival of the SE86
      wild type (WT) and attenuated strain was determined by bacterial count, and the
      tagged protein (ompR::3XFLAG cat::FLAG) was detected by SDS-PAGE and
      immunoblotting with anti-FLAG antibodies. RESULTS: Results showed that when
      exposed at 52oC, the acid-adapted SE86 WT cells were completely inactivated after
      300 minutes; however, non-adapted cells (WT and DeltaompR) and acid-adapted
      DeltaompR demonstrated higher thermal sensitivity, since they were completely
      inactivated in 240 minutes. At 60oC, the acid-adapted SE86 DeltaompR also
      demonstrated higher sensitivity that SE86 WT, being totally inactivated after 15
      minutes, while the WT cells were inactivated in 20 minutes. CONCLUSION: The acid
      adapted cells showed increased expression of OmpR when exposed to 52 oC and 60oC,
      this confirmed the requirement of acid adaptation  for S. Enteritidis SE86 to
      resist elevated temperatures.

PMID- 24727515
TI  - Glycemic control in the infectious diseases ward; role of clinical pharmacist
      interventions.
AB  - INTRODUCTION: Hyperglycemia is one of the most frequent metabolic complications
      in hospitalized patients. Increased risk of infection following hyperglycemia has
      been reported in hospitalized patients and infections may also cause insulin
      resistance which complicates the control of blood glucose level. In this study
      the impact of the clinical pharmacist interventions on the glycemic control in
      patients admitted to infectious diseases ward has been evaluated. METHODOLOGY: We
      conducted a prospective, pre-post interventional study among patients with
      hyperglycemia. The clinical pharmacist-led multidisciplinary team managed the
      glycemic profile of patients according to an established insulin protocol
      commonly used in internal wards. Clinical pharmacists reviewed patients' medical
      charts for proper insulin administration, evaluated nurses' technique for insulin
      injection and blood glucose measurement, and educated patients about symptoms of
      hypoglycemia and the importance of adherence to different aspects of their
      glycemic management. RESULTS: The percentage of controlled random blood sugar
      increased from 13.8% in the pre-intervention to 22.3% in the post-intervention
      group (p value < 0.01). On the other hand, the percentage of controlled fasting
      blood sugars in the post-intervention group was non-significantly higher than in
      the pre-intervention group. CONCLUSION: Pharmacists and additional health care
      providers from other departments such as nursing and dietary departments need to
      be devoted to glycemic control service. Collaborative practice agreement between
      physicians is necessary to promote this service and help to increase the use of
      such services in different settings for diabetes control.

PMID- 24727516
TI  - Vaginal infections among pregnant women at Omdurman Maternity Hospital in
      Khartoum, Sudan.
AB  - INTRODUCTION: Microbial infections of the vagina in pregnant women are health
      problems that lead to serious medical complications and consequences. This study
      aimed to investigate and determine antimicrobial susceptibilities of the
      causative agents of vaginal infections in pregnant women. METHODOLOGY: A cross
      sectional study of pregnant women (n = 200) was conducted between August and
      December 2008 at Omdurman Maternity Hospital, Khartoum, Sudan. Vaginal and
      cervical swabs were obtained from each subject and processed for isolation and
      identification of pathogenic microorganisms using standard methods of wet mount
      preparation, direct Gram smear, Nugent scoring system, direct immunofluorescence,
      and cultural techniques. Antimicrobial susceptibility testing of bacterial
      isolates was performed using standard procedures. Statistical analysis was done
      using SPSS program version 12.0.1. A p value < 0.05 was considered statistically
      significant. RESULTS: Of the 200 pregnant women enrolled, BV was detected in
      49.8%, followed by Chlamydia trachomatis (31.3%) and Candida albicans (16.6%),
      with low frequencies of Neisseria gonorrhoeae (1.8%) and Trichomonas vaginalis
      (0.5%). Higher infection rates were recorded among subjects in the third
      trimester (71.6%) than in the second trimester of gestation (28.4%). No
      significant association (p = 0.7) between history of abortions and C. trachomatis
      infections was found. Gentamicin was the most active agent against Gram-positive
      and Gram-negative bacteria. Clarythromycin was the most active against Mycoplasma
      species. CONCLUSIONS: Pregnant women with vaginal complaints revealed various
      positive microbiology results. Such cases may require specific medication.
      Routine culture of vaginal and cervical samples should be performed on all
      pregnant women during prenatal visits.

PMID- 24727517
TI  - Next-generation sequencing and bioinformatic approaches to detect and analyze
      influenza virus in ferrets.
AB  - INTRODUCTION: Conventional methods used to detect and characterize influenza
      viruses in biological samples face multiple challenges due to the diversity of
      subtypes and high dissimilarity of emerging strains. Next-generation sequencing
      (NGS) is a powerful technique that can facilitate the detection and
      characterization of influenza, however, the sequencing strategy and the
      procedures of data analysis possess different aspects that require careful
      consideration. METHODOLOGY: The RNA from the lungs of ferrets infected with
      influenza A/California/07/2009 was analyzed by next-generation sequencing (NGS)
      without using specific PCR amplification of the viral sequences. Several
      bioinformatic approaches were used to resolve the viral genes and detect viral
      quasispecies. RESULTS: The genomic sequences of influenza virus were
      characterized to a high level of detail when analyzing the short-reads with
      either the fast aligner Bowtie2, the general purpose aligner BLASTn or de novo
      assembly with Abyss. Moreover, when using distant viral sequences as reference,
      these methods were still able to resolve the viral sequences of a biological
      sample. Finally, direct sequencing of RNA samples did not provide sufficient
      coverage of the viral genome to study viral quasispecies, and, therefore, prior
      amplification of the viral segments by PCR would be required to perform this type
      of analysis. CONCLUSIONS: the introduction of NGS for virus research allows
      routine full characterization of viral isolates; however, careful design of the
      sequencing strategy and the procedures for data analysis are still of critical
      importance.

PMID- 24727518
TI  - Bacterial and viral etiology in hospitalized community acquired pneumonia with
      molecular methods and clinical evaluation.
AB  - INTRODUCTION: Polymerase chain reaction (PCR) method has improved the diagnosis
      rates for patients with community-acquired pneumonia (CAP). We aimed to evaluate
      the bacterial and viral etiology of hospitalized CAP cases and compare clinical
      and laboratory findings of patients with pure bacterial and bacterial and viral
      (mixed) infections. METHODOLOGY: A total of 55 patients hospitalized with CAP
      were enrolled into the prospective study between February 2010 and December 2010.
      Clinical and laboratory follow-up were performed on days 0, 7 and 14. Deep
      tracheal aspiration samples were examined for bacterial and viral pathogens by
      multiplex PCR, and standard bacteriological culture method. RESULTS: The
      etiological identification rate in 50 patients for bacteria, viruses and mixed
      virus-bacteria combination by PCR were 62%, 4%, 32%, respectively and 60% in 55
      patients by bacterial culture method. Streptococcus pneumoniae concomitant with
      Haemophilus influenzae (36%) and rhinovirus (16%) was very common, whereas
      atypical pathogens (only Mycoplasma pneumoniae) were rare (6%). Rhinovirus was
      the most common viral agent (20%). Recently identified viruses, human coronavirus
      HKU1 and human bocavirus were not detected except for human metapneumovirus (one
      case). There was no significant difference in terms of mean age, immune status,
      leukocyte count, C-reactive protein (CRP) values, hospitalization duration and
      CURB-65 score between bacterial and mixed viral-bacterial detections. Advanced
      age (p < 0.01) and higher CURB-65 score (p = 0.01) were found to be associated
      with increased mortality. CONCLUSION: Concomitance of bacterial and viral agents
      is frequent and resemble with bacterial infections alone. Further studies are
      needed for the clinical significance of mixed detections.

PMID- 24727519
TI  - Clinical manifestations and treatment outcomes in HIV-1-infected children
      receiving antiretroviral therapy in Karachi, Pakistan.
AB  - INTRODUCTION: The impact of antiretroviral (ARV) therapy on immunological and
      growth parameters in HIV-positive children in Pakistan has not been reported to
      date. METHODOLOGY: A retrospective chart review of children diagnosed with HIV at
      the Sindh AIDS Control Proigramme (SACP) and registered at the Aga Khan
      University, Karachi, between January 2005 and 2013 was conducted, evaluating
      clinical and laboratory profiles of HIV+ ARV+ children for ARV impact (serial
      height and weight CD4 and viral counts). RESULTS: Twenty-four children were
      diagnosed and registered as HIV positive over five years, and 20 were started on
      ARV. Six were excluded from analysis (ARV duration < 6 months). Nine (64.3%) of
      14 fulfilled WHO criteria for treatment failure at a median duration of 25 weeks
      (IQR 18-32) on ARV and underwent resistance genotyping. All nine had NNRTI
      resistance, two had high-grade NRTI resistance (>= 4 thymidine analog mutations).
      Median age at start of ARV was 71.5 weeks (IQR 37.5-119). Median baseline weight
      for age (WAZ) and height for age (HAZ) z-scores changed from -1.94 to 1.69 and 
      1.99 to -1.59, respectively, after six months of therapy. Median CD4 percentage
      and viral load at baseline changed from 13.8 to 17.8, while viral load changed
      from 285 * 104 copies to zero at six months. CONCLUSIONS: ARV improved absolute
      CD4 and viral counts. Weight and height did not  improve significantly,
      highlighting the need for aggressive nutritional rehabilitation. Early
      development of ARV resistance in these children requires formal assessment.

PMID- 24727520
TI  - Comparison of behaviors regarding live poultry exposure among rural residents in
      Vietnam and Thailand.
AB  - INTRODUCTION: Live poultry exposure and risk behaviors are more prevalent in
      rural communities, increasing the risk of influenza A/H5N1 infection. We examined
      the economic and socio-cultural influences on poultry-related practices by
      comparing the poultry-related practices among Vietnamese and Thai rural residents
      by family income and consumption preference. METHODS: Stratified cluster sampling
      was performed to select households. Within each household, one adult was randomly
      selected for a face-to-face interview in five Vietnamese and five Thai rural
      districts. Using a standardized questionnaire to assess domestic poultry
      husbandry, live poultry purchase, and demographics, logistic regression enabled
      comparisons of behaviors related to live poultry exposure and examination of
      associated factors. RESULTS: Among 994 Vietnamese and 907 Thai rural residents,
      live poultry exposure (prevalence of raising poultry, improper handling of sick
      or dead poultry, touching live poultry before buying, and slaughtering poultry at
      home) was more prevalent among Vietnamese than Thai respondents. After adjusting
      for other demographics, respondents with higher family incomes were less likely
      to rear backyard poultry in both Vietnam and Thailand, and with more likely to
      buy live poultry in Vietnam, but not in Thailand. Consumption preference for live
      poultry was associated with being more likely to rear backyard poultry in Vietnam
      and Thailand, and with being more likely to buy live poultry in Thailand, but not
      in Vietnam. CONCLUSION: The findings suggest important roles of economic
      imperatives and cultural preference for live poultry for consumption in
      supporting poultry rearing and live poultry purchase among rural residents.

PMID- 24727521
TI  - Knowledge and practice of universal precautions among health care workers in four
      national hospitals in Kabul, Afghanistan.
AB  - INTRODUCTION: This study aimed to assess the knowledge and practice of health
      care workers (HCWs) towards universal precautions (UPs) and to look into any
      associations between knowledge and practice. METHODOLOGY: A cross-sectional study
      was undertaken between August and October 2012, involving 300 HCWs from four
      national public hospitals in Kabul, Afghanistan. A self-administered
      questionnaire assessing the knowledge and practice of UPs was used. RESULTS:
      Among the 300 respondents, the mean knowledge score was 5.2 with a standard
      deviation (SD) of 1.5. On the practice score, the mean was 8.7 (SD = 2.2). A
      total of 90.6% and 70.8% of HCWs believed that UPs were necessary in contact with
      urine/feces and tears, respectively, although UPs are not necessary in these
      cases. On the other hand, 57.8% reported that they always recapped the needle
      after giving an injection, and 31.8% did not always change gloves in between
      patients. There were no associations between the knowledge and self-reported
      practice of UPs. CONCLUSIONS: The HCWs in Kabul had inadequate knowledge and poor
      practice of UPs. Training for HCWs is needed to encourage them to adhere to
      practice based on improved knowledge.

PMID- 24727522
TI  - Seroprevalence and molecular diagnosis of Toxoplasma gondii infection among blood
      donors in southern Iran.
AB  - INTRODUCTION: Toxoplasma gondii is a protozoan parasite which can be transmitted
      to human through a variety of routes including blood transfusion. This cross
      sectional study aimed to evaluate the seroprevalence of Toxoplasma infection and
      related epidemiological features among healthy blood donors. METHODOLOGY: A total
      of 1,480 healthy blood donors from five blood service centers in Fars province
      were analyzed for anti-Toxoplasma antibodies. Blood samples were tested for anti
      T. gondii IgG and IgM antibodies by enzyme immunoassay. IgM-positive samples were
      also tested for the presence of Toxoplasma DNA by Polymerase Chain Reaction
      (PCR). Demographic characteristics of participants were also recorded during
      samples collection. RESULTS: Anti T. gondii antibodies were detected in sera of
      286 out of 1,480 blood donors corresponding to an overall seroprevalence of 19.3%
      in this population.  From these, 182 (12.3%) were seropositive only for IgG, 81
      (5.47%) were seropositive only for IgM and 23 (1.6%) were positive for both IgG
      and IgM. PCR detected active parasitemia in two (1.9%) of the IgM-positive
      subjects. Age, place of residence and level of education were statistically
      significant (p < 0.05) with seropositivity to Toxoplasma. CONCLUSIONS: Our
      results highlighted that asymptomatic blood donors, especially those with active
      parasitemia, may constitute a significant risk of transmitting toxoplasmosis to
      susceptible recipients.

PMID- 24727523
TI  - Infective endocarditis due to Granulicatella adiacens: a case report and review.
AB  - Infective endocarditis (IE) caused by nutritionally variant Streptococci (NVS) is
      associated with high bacteriologic and treatment failure and mortality rates
      compared to endocarditis caused by other Streptococci. With automated blood
      culture systems, the rates of NVS-associated IE accounts for 5%-6% cases. We
      report a case of IE caused by NVS in an elderly female patient with no risk
      factors. The patient was successfully treated with combination antimicrobial
      therapy. 

PMID- 24727524
TI  - Hepatic encephalomyelopathy: a complication following liver cirrhosis caused by
      Budd-Chiari syndrome and HBV.
AB  - Progressive encephalomyelopathy is a rare neurological complication of chronic
      liver disease, even manifesting progressive spastic paraparesis. Few reports
      detailing the clinical and diagnostic aspects of this uncommon cause of
      neurological deterioration in patients with hepatic insufficiency have been
      published. Early recognition of this disorder will become more important in the
      future as patients with liver disease survive longer due to medical advances,
      including liver transplantation. The case of a patient with hepatic
      encephalomyelopathy associated with Budd-Chiari syndrome and HBV-related
      cirrhosis is presented. 

PMID- 24727525
TI  - Plasmodium ovale malaria in Brazil: report of an imported case with a prolonged
      incubation period.
AB  - We report the first case of imported Plasmodium ovale in Brazil, confirmed using
      both conventional microscopy and PCR-based protocols. The patient was a 36-year
      old Brazilian male who had been working as a miner in Cabinda Province, Angola.
      Based on his travel history, the parasite was dormant for at least two years. The
      relatively long period of incubation of P. ovale may obscure the link between
      exposure and disease. The recent increase in the number of people travelling to
      regions where P. ovale is endemic, suggests that a PCR-based protocol should be
      included as a complementary tool for malaria reference laboratories. 

PMID- 24727526
TI  - Vancomycin minimum inhibitory concentrations using different susceptibility
      methods in Staphylococcus aureus isolates.

PMID- 24727527
TI  - Controlled charged amino acids of Ti-binding peptide for surfactant-free
      selective adsorption.
AB  - The adsorption mechanism of titanium-binding peptide (TBP) on metal oxide
      substrates was investigated by evaluating the adsorption behavior of ferritins
      with various alanine-substituted TBPs. Results revealed that (a) a positively
      charged amino acid, lysine (K) or arginine (R), in TBP can anchor ferritin to
      negative zeta-potential substrates, (b) the adsorption force of K is stronger
      than R, and (c) local electrostatic interactions and flexibility of TBP directly
      affect adsorption. Based on these findings, selective ferritin adsorption on SiO2
      with TiOX patterned surfaces in a surfactant-free condition was demonstrated.
      Alanine-substituted TBP with one positively charged amino acid (K) and one
      negatively charged amino acid (D), achieved ferritin-selective adsorption without
      a surfactant. The importance of controlled electrostatic forces between TBP and a
      substrate for selective adsorption without a surfactant was clearly demonstrated.

PMID- 24727528
TI  - Mechanism of immonoglobulin G adsorption on mica-AFM and electrokinetic studies.
AB  - Adsorption of immunoglobulin G (IgG) from aqueous NaCl solutions of the
      concentration 10(-3)-0.15M on mica was studied. Initially, the kinetics was
      evaluated at pH 3.5 by direct AFM imaging. A monotonic increase in the maximum
      coverage of IgG with NaCl concentration was observed. These results were
      interpreted in terms of the theoretical model postulating an irreversible
      adsorption of the protein governed by the random sequential adsorption (RSA)
      model. Additionally, IgG adsorption and desorption was studied under in situ
      conditions, with streaming potential measurements. These measurements revealed
      that the maximum coverage of irreversibly adsorbed IgG varies from 0.37mgm(-2)
      for 10(-3)M, NaCl to 1.2mgm(-2) for 0.15M, NaCl. The significant role of ionic
      strength was attributed to the lateral electrostatic repulsion among adsorbed IgG
      molecules, positively charged at this pH value. These experimental results
      confirmed that monolayers of irreversibly bound IgG can be produced by adjusting
      ionic strength of the protein solution. In further experiments the stability and
      acid base properties of such monolayers were studied using the streaming
      potential method. It revealed that the monolayers were stable against pH cycling
      for the range from 3.5 to 9.5. The isoelectric point of mica supported IgG
      monolayers was 5.9, similar to derived from the micro-electrophoretic
      measurements in the bulk (5.8). Beside significance for basic sciences, the
      results indicate that thorough characteristics of IgG can be acquired via
      streaming potential measurements using microgram quantities of the protein. 

PMID- 24727529
TI  - Design and in vitro evaluation of a novel poly(methacrylic acid)/metronidazole
      antibacterial nanogel as an oral dosage form.
AB  - To overcome the undesirable side-effects of metronidazole (MTZ), ethylene glycol
      dimethacrylate is used as the cross-linker, and a series of poly(methacrylic
      acid) (PMAA) nanogels were prepared to load the MTZ. We investigated the
      morphology, size, in vitro release property in the simulated gastrointestinal
      medium, long-term antibacterial performance against Bacteroides fragilis,
      cytotoxicity, stability and activity of this novel MTZ/PMAA nanogel. The results
      indicate that the MTZ/PMAA nanogel sustained the release of MTZ in long-term
      antibacterial activity in the simulated gastrointestinal medium. This MTZ/PMAA
      nanogel exhibits less cytotoxicity than MTZ alone, suggesting that MTZ/PMAA
      nanogel is a more useful dosage form than MTZ for mild-to-moderate Clostridium
      difficile infections. The novel aspects of this study include the synthesis of a
      nanogel and the three-phase study of the release profile, which might be useful
      for other researchers in this field. 

PMID- 24727530
TI  - Effects of exposure to an extremely low frequency electromagnetic field on
      hippocampal long-term potentiation in rat.
AB  - Modern lifestyle exposes nearly all humans to electromagnetic fields,
      particularly to extremely low frequency electromagnetic fields (ELF-EMFs).
      Prolonged exposure to ELF-EMFs induces persistent changes in neuronal activity.
      However, the modulation of synaptic efficiency by ELF-EMFs in vivo is still
      unclear. In the present study, we investigated whether ELF-EMFs can change
      induction of long-term potentiation (LTP) and paired-pulse ratio (PPR) in the rat
      hippocampal area. Twenty-nine adult male Wistar rats were divided into 3 groups
      (ELF-EMF exposed, sham and control groups). The ELF-EMF group was exposed to a
      magnetic field for 90 consecutive days (2h/day). ELF-EMFs were produced by a
      circular coil (50Hz, 100 micro Tesla). The sham-exposed controls were placed in
      an identical chamber with no electromagnetic field. After this period, rats were
      deeply anesthetized with urethane (2.0mg/kg) and then a bipolar stimulating and
      recording electrode was implanted into the perforant pathway (PP) and dentate
      gyrus (DG), respectively. LTP in hippocampal area was induced by high-frequency
      stimulation (HFS). Prolonged exposure to ELF-EMFs increased LTP induction. There
      was a significant difference in the slope of EPSP and amplitude of PS between the
      ELF-EMF group and other groups. In conclusion, our data suggest that exposure to
      ELF-EMFs produces a marked change in the synaptic plasticity generated in
      synapses of the PP-DG. No significant difference in PPR of ELF-EMF group before
      and after HFS suggests a postsynaptic expression site of LTP. 

PMID- 24727531
TI  - Oligonucleotide-based therapy for neurodegenerative diseases.
AB  - Molecular genetics insight into the pathogenesis of several neurodegenerative
      diseases, such as Alzheimer's disease, Parkinson's disease, Huntington's disease
      and amyotrophic lateral sclerosis, encourages direct interference with the
      activity of neurotoxic genes or the molecular activation of neuroprotective
      pathways. Oligonucleotide-based therapies are recently emerging as an efficient
      strategy for drug development and these can be employed as new treatments of
      neurodegenerative states. Here we review advances in this field in recent years
      which suggest an encouraging assessment that oligonucleotide technologies for
      targeting of RNAs will enable the development of new therapies and will
      contribute to preservation of brain integrity.

PMID- 24727532
TI  - The breast-cancer-ization of cancer survivorship: implications for experiences of
      the disease.
AB  - Numerous observers have commented on the cultural prominence of breast cancer in
      North America. However, although popular and biomedical conceptions of cancer
      survivorship have been influenced to an inordinate degree by breast cancer, few
      researchers have examined the impact of dominant discourses on people diagnosed
      with other forms of cancer. Drawing on interviews with 32 Canadian men and women
      with a history of cancer conducted between 2010 and 2013, I demonstrate that
      breast cancer became central to their own experiences of cancer, providing an
      important lens through which to understand the effects of the disease. The
      effects of these comparisons were diverse, leading some participants to want to
      differentiate themselves from this implicit norm, leading others to downplay the
      seriousness of their own forms of suffering, and amplifying a sense of shame and
      stigma in yet others. 

PMID- 24727533
TI  - Assessing access to care for transgender and gender nonconforming people: a
      consideration of diversity in combating discrimination.
AB  - Transgender and gender nonconforming people face stigma and discrimination from a
      wide variety of sources and through numerous social realms. Stigma and
      discrimination originating from biomedicine and health care provision may impact
      this group's access to primary care. Such stigma and discrimination may originate
      not only from direct events and past negative experiences, but also through
      medicine's role in providing treatments of transitioning, the development of
      formal diagnoses to provide access to such treatments, and the medical language
      used to describe this diverse group. This paper examines the postponement of
      primary curative care among this marginalized group of people by drawing from the
      National Transgender Discrimination Survey, one of the largest available datasets
      for this underserved group. This paper also proposes an innovate categorization
      system to account for differences in self-conceptualization and identity, which
      has been of considerable concern for transgender and gender nonconforming
      communities but remains underexplored in social and health research. Results
      suggest that experience, identity, state of transition, and disclosure of
      transgender or gender nonconforming status are associated with postponement due
      to discrimination. Other findings suggest that postponement associated with
      primary place of seeking care and health insurance has ties to both
      discrimination and affordability. These findings highlight the importance of
      combating stigma and discrimination generated from within or experienced at sites
      of biomedicine or health care provision in improving access to care for this
      group of people. Improving access to care for all gender variant people requires
      a critical evaluation of existing research practices and health care provision to
      ensure that care is tailored as needed to each person's perspective in relation
      to larger social processes. 

PMID- 24727534
TI  - Examining regional variation in the use of cancer screening in Germany.
AB  - The detection of cancer in its early latent stages can improve a patient's
      chances of recovery and thereby reduce the overall burden of the disease. Cancer
      screening services are, however, only used by a small part of the population and
      utilization rates vary widely amongst the 402 German districts. This study
      examines to which extent geographic variation in the use of cancer screening can
      be explained by accessibility of these services and by spillover effects between
      adjacent areas, while controlling for a wide range of covariates. District level
      data on cancer screening utilization rates were calculated for breast, cervical,
      prostate, skin, and colorectal cancers using German data provided by the National
      Association of Statutory Health Insurance Physicians (Kassenarztliche
      Bundesvereinigung - KBV) between 2008 and 2011. We estimated the impact of health
      service variables on cancer screening utilization using spatial and non-spatial
      regression models. Spatial autocorrelation in the residuals was estimated using
      Moran's I statistic. After controlling for socioeconomic and other regional
      covariates, screening rates for breast, prostate, skin, and colorectal cancers
      are significantly higher in areas with higher physician density. The utilization
      of Pap-tests, skin cancer screening and colonoscopies is inversely related with
      average travel time to physicians. The coefficients for the spatial lag are
      significant and positive in all models. The positive spatial lags indicate that
      screening utilization rates are determined by knowledge spillovers between
      neighboring districts. In terms of public policy, our study demonstrates the
      potential to increase the use of cancer screening services through improving
      knowledge regarding cancer screening and by ensuring patient access to cancer
      screening services. 

PMID- 24727535
TI  - Comparison of biventricular and left ventricular assist devices for the
      management of severe right ventricular dysfunction in patients with end-stage
      heart failure.
AB  - Right ventricular failure (RVF) exposes ventricular assist device (VAD)
      recipients to a high risk of death, but its management has not yet been
      standardized. We report three separate management strategies used for VAD
      recipients that present with RVF at a single center: 1) Thoratec paracorporeal
      biventricular VAD implantation, 2) left ventricular assist device (LVAD)
      implantation with temporary CentriMag right ventricular assist device (RVAD), and
      3) LVAD combined with inotropic therapy. We retrospectively compared the
      preoperative data, the clinical outcomes, and the rates of adverse events in 84
      biventricular assist device (BiVAD) recipients and 89 LVAD recipients presenting
      with postoperative RVF (57 were treated with a temporary RVAD and 32 were managed
      medically). Risk factors for death were analyzed. The BiVAD recipients were
      significantly younger, more critically ill at the time of device implantation,
      and required extracorporeal membrane oxygenation, an intraaortic balloon pump,
      mechanical ventilation, inotropes, or cardiopulmonary resuscitation significantly
      more often (at the time of device implant) than the LVAD recipients with RVF. The
      6 month mortality was comparable in the two groups: 44 BiVAD patients (52%) and
      38 LVAD patients (43%). Age, previous cardiac surgery, low platelet count,
      increased creatinine levels, the use of preoperative mechanical ventilation, and
      the need for a temporary RVAD were associated with 6 month mortality. The
      occurrence of RVF at the time of device implantation is a severe situation; it is
      associated with excess mortality, even if it is managed using a BiVAD or a LVAD
      with a temporary RVAD, probably because of the high preoperative risk profiles of
      the patients. In all cases, RVF must be managed quickly. 

PMID- 24727536
TI  - The use of regional citrate anticoagulation continuous venovenous hemofiltration
      in extracorporeal membrane oxygenation.
AB  - Patients on extracorporeal membrane oxygenation (ECMO) frequently requires
      continuous renal replacement therapy (CRRT). Additional anticoagulation for the
      CRRT circuit is usually not employed, but this may increases the risk of clot
      embolization, which shortens oxygenator lifespan and increases patient's risk. We
      report our experience on the use of regional citrate anticoagulation continuous
      venovenous hemofiltration (RCA-CVVH) connected to an ECMO circuit, which could be
      useful during low heparin or heparin-free ECMO situations. Regional citrate
      anticoagulation continuous venovenous hemofiltration was performed using AK200US
      machine with a blood flow of 150 ml/min, Acid Citrate Dextrose Solution prefilter
      infusion at 240 ml/hr, ultrafiltration rate of 2,040 ml/hr, and postdilutional
      online generated replacement fluid infused as appropriate. The circuit was aimed
      to run for 30 hrs. From May 2009 to May 2013, 63 patients received ECMO and 29
      received RCA-CVVH. The median total CVVH time was 131 hrs (interquartile range
      [IQR]: 61-224 hrs), and hemofilter life was 27.2 hrs (IQR: 25.7-28.5 hrs). No
      hemofilter or oxygenator was changed because of clotting. Their hospital
      mortality was 27.6%. There were eight patients, who were judged to be too sick
      for anticoagulation, received predilution CRRT during the same period. Their
      hospital mortality was 75%. In conclusion, online postdilutional RCA-CVVH
      connected to an ECMO circuit is a feasible, safe, and effective CRRT technique. 

PMID- 24727537
TI  - von Willebrand factor multimers in pediatric extracorporeal membrane oxygenation
      support.
AB  - Acquired von Willebrand factor (vWF) disease is associated with a decrease in the
      amount of circulating high molecular weight (HMW) vWF multimers. vWF has not been
      previously investigated in children on extracorporeal membrane oxygenation (ECMO)
      support. We hypothesized that HMW vWF multimers and vWF activity decrease over
      the course of ECMO support in these patients. This prospective, single center,
      observational, cohort pilot study was carried out between December 2010 and April
      2011 and included patients 0 to 18 years old requiring ECMO support at our
      institution. Blood samples were tested for various aspects of vWF. Mean and
      standard deviation were estimated for vWF activity and multimers, whereas a
      generalized linear model was developed to estimate multimer changes over time.The
      study included six pediatric patients. The mean age of the patients was 54.9 +/-
      55.3 (mean +/- standard deviation) months. The mean HMW vWF multimer percentage
      was 23.4 +/- 7.3 in the pre-ECMO samples and significantly decreased over time
      (p<0.003). There was no significant change in low molecular weight vWF multimer
      percentage. An immediate decrease in vWF HMW multimers as a percentage of all
      multimers once ECMO is initiated was noted and persisted across the study period.

PMID- 24727538
TI  - Experience of Treatments of Amanita phalloides-Induced Fulminant Liver Failure
      with Molecular Adsorbent Recirculating System and Therapeutic Plasma Exchange.
AB  - Ingestion of the mushroom containing Amanita phalloides can induce fulminant
      liver failure and death. There are no specific antidotes. Blood purifications,
      such as molecular adsorbent recirculating system (MARS) and therapeutic plasma
      exchange (TPE), are potential therapies. However, the extent to which these
      technologies avert the deleterious effects of amatoxins remains controversial;
      the optimal intensity, duration, and initiation criteria have not been determined
      yet. This study aimed to retrospectively observe the effects of MARS and TPE on
      nine patients with A. phalloides-induced fulminant liver failure. The survival
      rate for the nine patients was 66.7%. Both TPE and MARS might remove toxins and
      improve liver functions. However, a single session of TPE produced immediately
      greater improvements in alanine aminotransferase (-60% vs. -16.3%), aspartate
      aminotransferase (-47.6% vs. -15.4%), and total bilirubin (-37.3% vs. -17.1%)
      (compared with the values of pretreatment, all p < 0.05) than MARS compared with
      MARS. Early intervention may be more effective than delayed therapy.
      Additionally, the presence of severe liver failure and renal failure indicated
      worse outcome. Although these findings are promising, additional case-controlled,
      randomized studies are required to confirm our results. 

PMID- 24727539
TI  - Total Artificial Heart as Bridge to Transplantation for Severe Culture-Negative
      Prosthetic Valve Endocarditis Due to Gemella haemolysans.
AB  - We report a rare case of a patient with prosthetic valve endocarditis (PVE)
      requiring implantation of a total artificial heart (TAH) as a bridge to heart
      transplantation. Gemella haemolysans, an unusual cause of PVE, was identified as
      the organism responsible only by 16s rRNA polymerase chain reaction analysis of
      surgical tissue samples. We also describe one of the first uses of combined TAH
      and veno-venous extracorporeal membrane oxygenation therapy in the setting of
      severe respiratory and cardiac failure. Implantation of a TAH may be considered
      in situations where more traditional reconstructive methods are not feasible. 

PMID- 24727540
TI  - Thrombus Formation Patterns in HeartMate II Continuous-Flow Left Ventricular
      Assist Devices: A Multifactorial Phenomenon Involving Kounis Syndrome?
AB  - Metallic devices are increasingly used in contemporary cardiological practice.
      They include coronary stents, artificial cardiac valves, bioprostheses for
      transcatheter aortic valve replacement, closure devices for patent foramen ovale
      and atrial septal defects, pacemakers, defibrillators, and left ventricular
      assist devices. Metals constitute the main components of these devices. Metal
      anions eluted from the components attached to circulating proteins can act as
      sensitizers able to induce hypersensitivity inflammation and thrombosis. Allergy
      to nickel occurs in up to one fourth of the population in several areas of the
      world and is the most frequent cause of allergic contact dermatitis. The
      HeartMate II device is made from titanium with ruby bearing. Titanium metal ions
      from HeartMate II are eluted through the action of blood, saline, proteins, and
      mechanical stress that can induce hypersensitivity and immune dysfunctions
      rendering titanium no longer biologically inert. An unexpected high rate of
      thrombosis with substantial morbidity and mortality has been observed with the
      use of this device, making the search of causality of thrombosis mandatory to
      predict and prevent this daunting complication. Although the cause of thrombosis
      seems to be multifactorial, careful history-taking regarding hypersensitivities,
      monitoring of inflammatory mediators, and lymphocyte transformation studies
      should be always performed in sensitive patients. 

PMID- 24727541
TI  - Prognoses of patients with acute-on-chronic hepatitis B liver failure are closely
      associated with altered SOCS1 mRNA expression and cytokine production following
      glucocorticoid treatment.
AB  - Suppressor of cytokine signaling (SOCS) 1 plays a crucial role in the immune
      response and might contribute to the prognoses of liver failure treated with
      glucocorticoid. We recruited 47 acute-on-chronic hepatitis B liver failure
      (ACHBLF) patients receiving glucocorticoid treatment and 30 healthy controls to
      determine the potential effects of glucocorticoid on the transcriptional level of
      SOCS1 in peripheral blood mononuclear cells. On the third and twenty-eighth days
      of glucocorticoid treatment, SOCS1 expression was negatively correlated with
      model for end-stage liver disease (MELD) score. Interleukin-6 (IL-6) and tumor
      necrosis factor-alpha (TNF-alpha) levels were statistically lower, while the
      SOCS1 transcription level was higher in survivors than non-survivors both in pre-
      and post-treatment ACHBLF patients. The methylation rate of the SOCS1 promoter in
      ACHBLF patients was higher than in healthy control patients as determined by
      methylation-specific polymerase chain reaction. The mRNA level of SOCS1 in
      methylated promoters was significantly lower than from patients with unmethylated
      SOCS1 promoters. interferon (IFN)-gamma-responsive and STAT1-dependent gene
      expression was higher in survivors and was dramatically decreased with rising
      expression of SOCS1 after glucocorticoid treatment. Mortality rates were
      significantly higher in methylated patients than for those without methylation at
      the end of a 90-day follow-up. Furthermore, we found that five in six surviving
      patients displayed demethylated SOCS1 on the twenty-eighth day after treatment,
      while that number was 3 in 10 in the non-survivors. These findings suggested that
      ACHBLF patients without SOCS1 methylation may have a favorable response to
      corticosteroid treatment. 

PMID- 24727543
TI  - Development of a doxycycline-inducible lentiviral plasmid with an instant
      regulatory feature.
AB  - Lentiviruses provide highly efficient gene delivery vehicles in both dividing and
      non-dividing cells. Inducible gene expression systems often employ a specific
      cell line that constitutively expresses a regulatory protein for transgene
      expression. As one of such inducible expression systems the Tet-On system uses a
      cell line expressing reverse tetracycline-responsive transcriptional activator
      (rtTA). The rtTA protein binds to the tetracycline-responsive element (TRE) in
      the promoter and activates transcription of a transgene in a doxycycline
      dependent manner. To establish a universal and instant regulatory system without
      generating Tet-On cell lines, the cDNAs of rtTA and a testing target gene (PPM1B)
      were cloned in the bi-directional TRE-containing promoters. Here, we examined
      whether a basal leaky expression of rtTA allows instantly inducible expression of
      both rtTA itself and the target gene, PPM1B in a single plasmid using the two
      mini-CMV promoters. Transient transfection of the lentiviral plasmids into human
      embryonic kidney HEK293T cells showed a significant induction of PPM1B expression
      in response to doxycycline, suggesting that these lentiviral plasmids can be used
      as an instantly inducible mammalian expression vector. However, the expression of
      rtTA by lentiviral transduction shows a minimal expression without a consistent
      response to doxycycline, suggesting that the utility of these lentiviral vectors
      is limited. A potential solution to overcome lentiviral transgene inactivation is
      proposed. 

PMID- 24727542
TI  - Chemerin aggravates DSS-induced colitis by suppressing M2 macrophage
      polarization.
AB  - Chemerin is present in various inflammatory sites and is closely involved in
      tissue inflammation. Recent studies have demonstrated that chemerin treatment can
      cause either anti-inflammatory or pro-inflammatory effects according to the
      disease model being investigated. Elevated circulating chemerin was recently
      found in patients with inflammatory bowel disease (IBD); however, the role of
      chemerin in intestinal inflammation remains unknown. In this study, we
      demonstrated that the administration of exogenous chemerin (aa17-156) aggravated
      the severity of dextran sulfate sodium (DSS)-induced colitis, which was
      characterized by higher clinical scores, extensive mucosal damage and
      significantly increased local and systemic production of pro-inflammatory
      cytokines, including IL-6, TNF-alpha and interferon (IFN-gamma). Interestingly,
      chemerin did not appear to influence the magnitudes of inflammatory infiltrates
      in the colons, but did result in significantly decreased colonic expression of M2
      macrophage-associated genes, including Arginase 1 (Arg-1), Ym1, FIZZ1 and IL-10,
      following DSS exposure, suggesting an impaired M2 macrophage skewing in vivo.
      Furthermore, an in vitro experiment showed that the addition of chemerin directly
      suppressed M2 macrophage-associated gene expression and STAT6 phosphorylation in
      IL-4-stimulated macrophages. Significantly elevated chemerin levels were found in
      colons from DSS-exposed mice and from ulcerative colitis (UC) patients and
      appeared to positively correlate with disease severity. Moreover, the in vivo
      administration of neutralizing anti-chemerin antibody significantly improved
      intestinal inflammation following DSS exposure. Taken together, our findings
      reveal a pro-inflammatory role for chemerin in DSS-induced colitis and the
      ability of chemerin to suppress the anti-inflammatory M2 macrophage response. Our
      study also suggests that upregulated chemerin in inflamed colons may contribute
      to the pathogenesis of IBD. 

PMID- 24727544
TI  - An unusual case of abdominal distension.

PMID- 24727545
TI  - Reply: To PMID 24216467.

PMID- 24727546
TI  - Motif-independent prediction of a secondary metabolism gene cluster using
      comparative genomics: application to sequenced genomes of Aspergillus and ten
      other filamentous fungal species.
AB  - Despite their biological importance, a significant number of genes for secondary
      metabolite biosynthesis (SMB) remain undetected due largely to the fact that they
      are highly diverse and are not expressed under a variety of cultivation
      conditions. Several software tools including SMURF and antiSMASH have been
      developed to predict fungal SMB gene clusters by finding core genes encoding
      polyketide synthase, nonribosomal peptide synthetase and dimethylallyltryptophan
      synthase as well as several others typically present in the cluster. In this
      work, we have devised a novel comparative genomics method to identify SMB gene
      clusters that is independent of motif information of the known SMB genes. The
      method detects SMB gene clusters by searching for a similar order of genes and
      their presence in nonsyntenic blocks. With this method, we were able to identify
      many known SMB gene clusters with the core genes in the genomic sequences of 10
      filamentous fungi. Furthermore, we have also detected SMB gene clusters without
      core genes, including the kojic acid biosynthesis gene cluster of Aspergillus
      oryzae. By varying the detection parameters of the method, a significant
      difference in the sequence characteristics was detected between the genes
      residing inside the clusters and those outside the clusters. 

PMID- 24727548
TI  - Prevalence of the sickle cell trait in Gabon: a nationwide study.
AB  - Sickle Cell Disease (SCD) is an important cause of death in young children in
      Africa, which the World Health Organization has declared a public health
      priority. Although SCD has been studied at the continental scale and at the local
      scale, a picture of its distribution at the scale of an African country has never
      been given. The aim of this study is to provide such a picture for the Republic
      of Gabon, a country where precisely the epidemiology of SCD has been poorly
      investigated. To this effect, 4250 blood samples from persons older than 15 were
      collected between June 2005 and September 2008 in 210 randomly selected villages
      from the nine administrative provinces of Gabon. Two methods were used to screen
      Sickle Cell Trait (SCT) carriers: isoelectric focusing (IEF) and high-performance
      liquid chromatography (HPLC). SCT prevalence in Gabon was 21.1% (895/4249). SCT
      prevalence was significantly larger for the Bantu population (21.7%, n=860/3959)
      than for the Pygmy population (12.1%, n=35/290), (p=0.00013). In addition, the
      presence of Plasmodium sp. was assessed via thick blood examination. Age was
      positively associated with SCT prevalence (odds-ratio for an increase of 10 years
      in age=1.063, p=0.020). Sex was not associated with SCT prevalence. The study
      reveals the absence of homozygous sickle-cell patients, and marked differences in
      SCT prevalence between the Gabonese provinces, and also between population groups
      (Bantu vs Pygmy). These findings could be used by the public health authorities
      to allocate medical resources and target prevention campaigns.

PMID- 24727547
TI  - Glutaredoxin-2 is required to control oxidative phosphorylation in cardiac muscle
      by mediating deglutathionylation reactions.
AB  - Glutaredoxin-2 (Grx2) modulates the activity of several mitochondrial proteins in
      cardiac tissue by catalyzing deglutathionylation reactions. However, it remains
      uncertain whether Grx2 is required to control mitochondrial ATP output in heart.
      Here, we report that Grx2 plays a vital role modulating mitochondrial energetics
      and heart physiology by mediating the deglutathionylation of mitochondrial
      proteins. Deletion of Grx2 (Grx2(-/-)) decreased ATP production by complex I
      linked substrates to half that in wild type (WT) mitochondria. Decreased
      respiration was associated with increased complex I glutathionylation diminishing
      its activity. Tissue glucose uptake was concomitantly increased. Mitochondrial
      ATP output and complex I activity could be recovered by restoring the redox
      environment to that favoring the deglutathionylated states of proteins. Grx2(-/-)
      hearts also developed left ventricular hypertrophy and fibrosis, and mice became
      hypertensive. Mitochondrial energetics from Grx2 heterozygotes (Grx2(+/-)) were
      also dysfunctional, and hearts were hypertrophic. Intriguingly, Grx2(+/-) mice
      were far less hypertensive than Grx2(-/-) mice. Thus, Grx2 plays a vital role in
      modulating mitochondrial metabolism in cardiac muscle, and Grx2 deficiency leads
      to pathology. As mitochondrial ATP production was restored by the addition of
      reductants, these findings may be relevant to novel redox-related therapies in
      cardiac disease. 

PMID- 24727549
TI  - Biosorption of uranium on Bacillus sp. dwc-2: preliminary investigation on
      mechanism.
AB  - In this paper, the biosorption mechanisms of uranium on an aerobic Bacillus sp.
      dwc-2, isolated from a potential disposal site for (ultra-) low uraniferous
      radioactive waste in Southwest China, was explored by transmission electron
      microscopy (TEM), energy dispersive X-ray (EDX) analysis, FT-IR spectroscopy,
      proton induced X-ray emission (PIXE) and enhanced proton backscattering
      spectrometry (EPBS). The biosorption experiments for uranium were carried out at
      a low pH (pH 3.0), where the uranium solution speciation is dominated by highly
      mobile uranyl ions. The bioaccumulation was found to be the potential mechanism
      involved in uranium biosorption by Bacillus sp. dwc-2, and the bioaccumulated
      uranium was deposited in the cell interior as needle shaped particles at pH 3.0,
      as revealed by TEM analysis as well as EDX spectra. FTIR analysis further
      suggested that the absorbed uranium was bound to amino, phosphate and carboxyl
      groups of bacterial cells. Additionally, PIXE and EPBS results confirmed that ion
      exchange also contributed to the adsorption process of uranium. All the results
      implied that the biosorption mechanism of uranium on Bacillus sp. is complicated
      and at least involves bioaccumulation, ion exchange and complexation process. 

PMID- 24727550
TI  - Shipboard determination of radiocesium in seawater after the Fukushima accident:
      results from the 2011-2012 Russian expeditions to the Sea of Japan and western
      North Pacific Ocean.
AB  - A total of 88 seawater samples were collected during two Russian research
      expeditions (April-May 2011 and August-September 2012) to the Sea of Japan, the
      Oyashio Current region near Kuril Islands and the Kuroshio-Oyashio transition
      area in the western North Pacific Ocean. The observations were made aboard the
      R/V Pavel Gordienko and Akademik Shokalsky in order to study the impact of the
      Fukushima accident on radioactive contamination of the marine environment. On the
      board of a ship, the water samples were passed through filters to retain
      particles with the size of >1 micron. Cesium was extracted from the large volumes
      (100-3000 L) of the filtrated water using a selective fiber chemisorbent
      impregnated with copper ferrocyanide. Measurements of (134)Cs and (137)Cs
      activities in 83 samples of sorbents and 21 samples of filters were performed in
      the ship-based laboratory with a semiconductor HP-Ge detector. The quantified
      activity concentrations of dissolved radiocesium ranged from 1 Bq m(-3) to 34 Bq
      m(-3) for (137)Cs and from 0.2 Bq m(-3) to 29 Bq m(-3) for (134)Cs. Activity
      concentrations of (137)Cs and (134)Cs were strongly correlated with each other (r
      = 0.993, n = 59). The (137)Cs/(134)Cs activities ratio in the Fukushima-derived
      radiocesium inventory for the study areas was deduced to be 0.99 +/- 0.03 (on 15
      March 2011) and the pre-Fukushima background level of (137)Cs in seawater was
      estimated as 1.3 +/- 0.3 Bq m(-3). The lowest activities of both isotopes were
      determined in the western part of the Sea of Japan near the Russian coast, while
      the maximal levels were observed in the open Pacific Ocean, some 500-800 km
      offshore the Fukushima Dai-ichi Nuclear Power Plant. Contamination with (134)Cs
      at a level of 0.3-2.6 Bq m(-3) was registered in seawater samples collected in
      2011 near the Kuril Islands and Kamchatka in the Oyashio Current region. During
      the period from April-May 2011 to August-September 2012, activity concentrations
      of (137)Cs and (134)Cs in surface waters had decreased for all seven stations
      repeatedly sampled in the study. A detailed observation of radiocesium
      distribution within the water column down to the depth of 200 m at nine stations
      from the Kuroshio-Oyashio Interfrontal Zone and Kuroshio Extension in 2012
      revealed maximal activity concentrations of both cesium radionuclides in the 100
      200 m depth layer. The average inventory of Fukushima-derived (137)Cs in the top
      200 m of the water column for the nine stations was estimated as 1.19 kBq m(-2)
      (decay corrected to 15 March 2011) which is 4.6 times higher than the background
      value of 0.26 kBq m(-2) expected for this depth. The monitoring results obtained
      in the study and relevant data published by others show that following the
      Fukushima accident, the Oyashio current acts as a provider of low-contaminated
      subarctic waters to the heavily contaminated Kuroshio-Oyashio mixed water region.

PMID- 24727551
TI  - Clerodendrum serratum (L.) Moon. - a review on traditional uses, phytochemistry
      and pharmacological activities.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Clerodendrum serratum (L.) Moon. (Verbenaceae) is
      an important medicinal plant growing in the tropical and warm temperate regions
      like Africa, Southern Asia; Malaysia and distributed throughout in forests of
      India and Sri Lanka. It is traditionally valued and reported for treating pain,
      inflammation, rheumatism, respiratory disorders, fever and malarial fever in
      India with a long history. To provide a comprehensive overview of the traditional
      and ethno medicinal uses, phytochemistry and biological activities of C. serratum
      with clinical and toxicity data and possibly make recommendations for further
      research. MATERIALS AND METHODS: All relevant worldwide accepted databases were
      searched for the terms "Clerodendrum", "Clerodendrum serratum", "Bharangi" and
      "Cheruthekku" along with the other literature from Indian classical texts and
      pharmacopoeias. There was no specific timeline set for the search. The accessible
      literatures available on C. serratum were collected via electronic search using
      Pubmed, Scopus, Science Direct and traditional books reports on ethnopharmacology
      and traditional medicines. RESULTS: C. serratum has played an important role in
      Indian system of medicine. In addition to the common local use in respiratory
      diseases, other ethnomedicinal uses include treatment of pain, inflammation,
      rheumatism and fever especially malarial fever. Scientific studies on extracts
      and formulations revealed anti-asthmatic, mast cell stabilization and anti
      allergic effects of roots of C. serratum. Reported data on pharmacological
      activities also includes hepatoprotective, anti-oxidant, anti-inflammatory and
      anticancer potential of the drug. Saponins (terpenoids and steroids), flavonoids
      and phenolics isolated from roots have been the focus of phytochemical
      investigations as the biological activity has been ascribed to the saponins,
      which are known to possess anti-inflammatory and anti-cancer activity. Isolated
      bioactives from roots like icosahydropicenic acid and ursolic acid have been
      claimed to offer anti-allergic and hepatoprotective activity. CONCLUSIONS:
      Therapeutic potential of roots and leaves of C. serratum has been demonstrated in
      the conditions like asthma, allergy, fever, inflammation and liver disorders
      attributed to the presence of various flavonoids, phenolics and saponins present
      in the drug. Many ethnobotanical claims have been confirmed through modern in
      vitro and in-vivo pharmacological studies of different extracts and isolates from
      plant; however, additional studies on the biomarkers are needed to establish
      mechanism of action and to validate the traditional use of this drug in clinical
      practices after proper safety assessment.

PMID- 24727552
TI  - Influence of sulfate and phosphate on the deposition of plasmid DNA on silica and
      alumina-coated surfaces.
AB  - The influence of sulfate and phosphate on the deposition kinetics of plasmid DNA
      on solid surfaces was examined at a constant 300mM ionic strength in both NaCl
      Na2SO4 and NaCl-NaH2PO4-Na2HPO4 mixing solutions with varied sulfate and
      phosphate concentrations at pH 6.0 by utilizing a quartz crystal microbalance
      with dissipation (QCM-D). Two representative solid surfaces, both silica and
      alumina-coated surfaces, were concerned in this study. To better understand the
      effects of sulfate and phosphate on plasmid DNA deposition, QCM-D data were
      complemented by diffusion coefficients and zeta potentials of DNA as a function
      of examined solution conditions. The presence of sulfate and phosphate in
      solutions decreased the deposition efficiencies of plasmid DNA on both silica and
      alumina-coated surfaces. Moreover, the deposition efficiencies decreased with
      increasing concentrations of sulfate/phosphate. With sulfate/phosphate ions
      present in solutions, the deposition kinetics of plasmid DNA on both silica and
      alumina-coated surfaces were mainly controlled by classic Derjaguin-Landau-Verwey
      Overbeek (DLVO) interactions. 

PMID- 24727553
TI  - Further aspects of ochratoxin A-cation interactions: complex formation with zinc
      ions and a novel analytical application of ochratoxin A-magnesium interaction in
      the HPLC-FLD system.
AB  - Ochratoxin A (OTA) is a mycotoxin produced by different Aspergillus and
      Penicillium species. Since its mechanism of action is not fully understood yet,
      it is important to gain further insight into different interactions of OTA at the
      molecular level. OTA is found worldwide in many foods and drinks. Moreover, it
      can also be detected in human and animal tissues and body fluids, as well.
      Therefore, the development of highly sensitive quantitative methods for the
      determination of OTA is of utmost importance. OTA most likely forms complexes
      with divalent cations, both in cells and body fluids. In the present study, the
      OTA-zinc interaction was investigated and compared to OTA-magnesium complex
      formation using fluorescence spectroscopy and molecular modeling. Our results
      show that zinc(II) ion forms a two-fold higher stable complex with OTA than
      magnesium(II) ion. In addition, based on the enhanced fluorescence emission of
      OTA in its magnesium-bound form, a novel RP-HPLC-fluorescence detector (FLD)
      method was also established. Our results highlight that the application of
      magnesium chloride in alkaline eluents results in an approximately two-fold
      increase in sensitivity using the HPLC-FLD technique. 

PMID- 24727554
TI  - Systemic growth of F. graminearum in wheat plants and related accumulation of
      deoxynivalenol.
AB  - Fusarium head blight (FHB) is an important disease of wheat worldwide caused
      mainly by Fusarium graminearum (syn. Gibberella zeae). This fungus can be highly
      aggressive and can produce several mycotoxins such as deoxynivalenol (DON), a
      well known harmful metabolite for humans, animals, and plants. The fungus can
      survive overwinter on wheat residues and on the soil, and can usually attack the
      wheat plant at their point of flowering, being able to infect the heads and to
      contaminate the kernels at the maturity. Contaminated kernels can be sometimes
      used as seeds for the cultivation of the following year. Poor knowledge on the
      ability of the strains of F. graminearum occurring on wheat seeds to be
      transmitted to the plant and to contribute to the final DON contamination of
      kernels is available. Therefore, this study had the goals of evaluating: (a) the
      capability of F. graminearum causing FHB of wheat to be transmitted from the
      seeds or soil to the kernels at maturity and the progress of the fungus within
      the plant at different growth stages; (b) the levels of DON contamination in both
      plant tissues and kernels. The study has been carried out for two years in a
      climatic chamber. The F. gramineraum strain selected for the inoculation was
      followed within the plant by using Vegetative Compatibility technique, and
      quantified by Real-Time PCR. Chemical analyses of DON were carried out by using
      immunoaffinity cleanup and HPLC/UV/DAD. The study showed that F. graminearum
      originated from seeds or soil can grow systemically in the plant tissues, with
      the exception of kernels and heads. There seems to be a barrier that inhibits the
      colonization of the heads by the fungus. High levels of DON and F. graminearum
      were found in crowns, stems, and straw, whereas low levels of DON and no
      detectable levels of F. graminearum were found in both heads and kernels.
      Finally, in all parts of the plant (heads, crowns, and stems at milk and vitreous
      ripening stages, and straw at vitreous ripening), also the accumulation of
      significant quantities of DON-3-glucoside (DON-3G), a product of DON
      glycosylation, was detected, with decreasing levels in straw, crown, stems and
      kernels. The presence of DON and DON-3G in heads and kernels without the
      occurrence of F. graminearum may be explained by their water solubility that
      could facilitate their translocation from stem to heads and kernels. The presence
      of DON-3G at levels 23 times higher than DON in the heads at milk stage without
      the occurrence of F. graminearum may indicate that an active glycosylation of DON
      also occurs in the head tissues. Finally, the high levels of DON accumulated in
      straws are worrisome since they represent additional sources of mycotoxin for
      livestock. 

PMID- 24727556
TI  - Urgent announcement of article retraction.

PMID- 24727555
TI  - Maternal exposure to criteria air pollutants and congenital heart defects in
      offspring: results from the national birth defects prevention study.
AB  - BACKGROUND: Epidemiologic literature suggests that exposure to air pollutants is
      associated with fetal development. OBJECTIVES: We investigated maternal exposures
      to air pollutants during weeks 2-8 of pregnancy and their associations with
      congenital heart defects. METHODS: Mothers from the National Birth Defects
      Prevention Study, a nine-state case-control study, were assigned 1-week and 7
      week averages of daily maximum concentrations of carbon monoxide, nitrogen
      dioxide, ozone, and sulfur dioxide and 24-hr measurements of fine and coarse
      particulate matter using the closest air monitor within 50 km to their residence
      during early pregnancy. Depending on the pollutant, a maximum of 4,632 live-birth
      controls and 3,328 live-birth, fetal-death, or electively terminated cases had
      exposure data. Hierarchical regression models, adjusted for maternal demographics
      and tobacco and alcohol use, were constructed. Principal component analysis was
      used to assess these relationships in a multipollutant context. RESULTS: Positive
      associations were observed between exposure to nitrogen dioxide and coarctation
      of the aorta and pulmonary valve stenosis. Exposure to fine particulate matter
      was positively associated with hypoplastic left heart syndrome but inversely
      associated with atrial septal defects. Examining individual exposure-weeks
      suggested associations between pollutants and defects that were not observed
      using the 7-week average. Associations between left ventricular outflow tract
      obstructions and nitrogen dioxide and between hypoplastic left heart syndrome and
      particulate matter were supported by findings from the multipollutant analyses,
      although estimates were attenuated at the highest exposure levels. CONCLUSIONS:
      Using daily maximum pollutant levels and exploring individual exposure-weeks
      revealed some positive associations between certain pollutants and defects and
      suggested potential windows of susceptibility during pregnancy.

PMID- 24727557
TI  - N-Hydroxycinnamide derivatives of osthole inhibit cell migration and invasion by
      suppressing Smad2 and Akt pathways in human colorectal adenocarcinoma cells.
AB  - WJ1376-1 and WJ1398-1 are new synthetic compounds developed based on the
      structure of the Chinese herbal medicine osthole. Previously, we reported that
      WJ1376-1 and WJ1398-1 can induce cell-cycle arrest by activating ATR kinase
      (ataxia telangiectasia and rad3 related kinase) and inhibiting the
      phosphorylation of Aurora A kinase. In this study, we determined that WJ1376-1
      and WJ1398-1 strongly inhibited the migration and invasion in human colorectal
      cancer cells at concentrations as low as 1MUM. In the transforming growth factor
      (TGF)-beta-induced epithelial-mesenchymal transition model, WJ1376-1 and WJ1398-1
      potently downregulated the transcription factor Snail1, the mesenchymal protein
      vimentin, and matrix metalloprotease-9, but upregulated the epithelial protein E
      cadherin. WJ1376-1 and WJ1398-1 also inhibited the TGF-beta-induced
      phosphorylation of Smad2 and of Akt at Ser 473, and the nuclear translocation of
      Smad2 was substantially lower in WJ1376-1- and WJ1398-1-treated cells than it was
      in control cells. In transient transfection experiments, we observed that WJ1376
      1 and WJ1398-1 strongly inhibited TGF-beta-stimulated activity of a Smad
      reporter. Finally, WJ1376-1 and WJ1398-1 blocked TGF-beta-induced phosphorylation
      of the TGF-beta Type I receptor (TGF-betaRI). These results suggest that WJ1376-1
      and WJ1398-1 inhibit cell migration and invasion by suppressing TGF-betaRI
      phosphorylation and subsequently hindering both Smad2 and phosphatidylinositol 3
      kinase/Akt signaling pathways. 

PMID- 24727558
TI  - New chiral 4-substituted 2-cyanoethyl-oxazolines: synthesis and assessment of
      some biological activities.
AB  - This paper describes the synthesis of new enantiomerically pure 2-cyanoethyl
      oxazolines in one step starting from a wide range of amino alcohols and 4-ethoxy
      4-iminobutanenitrile with high to good yields (73-96%) via an appropriate
      procedure which can be used for a selective synthesis of mono-oxazolines. A
      simple operation as well as a practical separation is additional eco-friendly
      attributes of this method. All the synthesized compounds were identified and
      characterized with their physicochemical features and their spectral data ((1)H
      NMR, (13)C NMR and TOFMS ES(+)). Among the prepared mono-oxazolines, the mono
      oxazoline (3a) [3-[(4S)-4-benzyl-4,5-dihydro-1,3-oxazol-2-yl] propanenitrile] was
      tested to detect some biological activities. This compound was studied in vitro
      given the various types of pharmacological properties characterizing these
      compounds such as antioxidant, antimicrobial and analgesic activities. The
      antioxidant activity and mechanism of (3a) were identified using various in vitro
      antioxidant assays including 1,1-diphenyl-2-picryl-hydrazyl (DPPH), and
      superoxide anion radicals (O2(-)) scavenging activity. In addition, compared to
      Quercetin, the tested synthetic product reveals a relatively-strong antiradical
      activity towards the DPPH (activity percentage of 81.22%) free radicals and
      significantly decreased the reactive oxygen species such as (O2(-)) formation
      evaluated by the non-enzymatic (nitroblue tetrazolium/riboflavine) and the
      enzymatic (xanthine/xanthine oxidase) systems. Related activity values were,
      respectively, 66% and 60.30%. The oxazoline (3a) showed a high ability to reduce
      the O2(-) generation and proved to be a very potent radical scavenger. On the
      other hand, the analgesic property of the 3[(4S)-benzyl-4,5-dihydro-1,3-oxazol-2
      yl] propanenitrile (3a) was demonstrated. The subcutaneous administration of (3a)
      produced a significant reduction in the number of abdominal constrictions
      amounting to 73.81% in the acetic acid writhing test in mice. In addition to
      these advances, the oxazoline (3a) has been investigated as an antimicrobial
      agent. Our results showed that this molecule exhibited various levels of
      antibacterial effect against all the tested bacterial strains. 

PMID- 24727559
TI  - Motor planning in Parkinson's disease patients experiencing freezing of gait: the
      influence of cognitive load when approaching obstacles.
AB  - Freezing of gait (FOG) in Parkinson's disease (PD) is typically assumed to be a
      pure motor deficit, although it is important to consider how an abrupt loss of
      gait automaticity might be associated with an overloaded central resource
      capacity. If resource capacity limits are a factor underlying FOG, then obstacle
      crossing may be particularly sensitive to dual task effects in eliciting FOG.
      Participants performed a dual task (auditory digit monitoring) in order to
      increase cognitive load during obstacle crossing. Forty-two non-demented
      participants (14 PD patients with FOG, 13 PD who do not freeze, and 14 age
      matched healthy control participants) were required to walk and step over a
      horizontal obstacle set at 15% of the participants' height. Kinematic data were
      split into two phases of their approach: early (farthest away from the obstacle),
      and late (just prior to the obstacle). Interestingly, step length variability and
      step time variability increased when PD patients with FOG performed the dual
      task, but only in the late phase prior to the obstacle (i.e. when closest to the
      obstacle). Additionally, immediately after crossing, freezers landed the lead
      foot abnormally close to the obstacle regardless of dual task condition, and also
      contacted the obstacle more frequently (planning errors). Strength of the dual
      task effect was associated with low general cognitive status, declined executive
      function, and inappropriate spatial planning, but only in the PD-FOG group. This
      study is the first to demonstrate that cognitive load differentially impacts
      planning of the final steps needed to avoid an obstacle in PD patients with
      freezing, but not non-freezers or healthy controls, suggesting specific neural
      networks associated with FOG behaviours. 

PMID- 24727560
TI  - Effect of unemployment on cardiovascular risk factors and mental health.
AB  - BACKGROUND: Following the economic changes in Poland, increasing health
      discrepancies were observed during a period of 20 years, which may be partly
      attributable to the consequences of unemployment. AIMS: To assess the association
      between unemployment, major cardiovascular risk factors and mental health.
      METHODS: A cross-sectional study in which data were collected between 2009 and
      2010 during preventive health examinations by an occupational medicine service in
      Gdansk, Poland. Data on blood pressure, resting heart rate, information about
      smoking habits, body mass index and history of use of mental health services were
      collected during these assessments. Multiple logistic regression was used during
      data analysis to adjust for age, gender, education and length of employment.
      RESULTS: Study participants comprised 3052 unemployed and 2059 employed
      individuals. After adjustment for age, gender, education and number of previous
      employments, the odds ratio (OR) for hypertension in relation to unemployment was
      1.02 [95% confidence interval (95% CI) 0.84-1.23]. There was a statistically
      significant negative association between being overweight and unemployment (OR =
      0.81, 95% CI: 0.66-0.99). Smoking was positively associated with unemployment
      after adjustment for age and sex (OR = 1.45, 95% CI: 1.25-1.67). There was a
      positive relationship between mental ill-health and unemployment among study
      participants (OR = 2.05, 95% CI: 0.91-4.65), but this was not statistically
      significant. CONCLUSIONS: The patterns of major cardiovascular risk factors
      differed between unemployed and employed individuals in Poland. Our observations
      suggest employment status is a predictor of specific disease risk profiles;
      consequently, specific preventive measures are needed in unemployed individuals.

PMID- 24727561
TI  - Psycho-behavioural risks of low back pain in railway workers.
AB  - BACKGROUND: Low back pain (LBP) is the most costly ailment in the work force.
      Risky work behaviour and psychological stress are established risk factors. AIMS:
      To explore the associations between workplace risk factors, psychological stress
      and LBP among Malaysian railway workers. METHODS: A cross-sectional study was
      carried out on railway workers in Malaysia. Socio-demographics, workplace risk
      factors for LBP, perceived psychological stress and history of LBP over the
      previous month were obtained by direct interviews using a structured closed-ended
      questionnaire. Descriptive, bivariate and logistic regression analyses were
      conducted. RESULTS: There were 513 study participants (70% response rate). The
      prevalence of LBP in the previous month was 69%. Multivariate analysis yielded
      four significant predictors of LBP: employment of >= 10 years, lifting and
      lowering heavy loads, prolonged standing posture and psychological stress.
      CONCLUSIONS: The high prevalence of LBP and its significant associations with
      physical and psychological stress factors in railway workers points to an urgent
      need for preventive measures, particularly among workers in high-risk
      occupations.

PMID- 24727562
TI  - Workforce coverage by GB occupational physicians and disease incidence rates.
AB  - BACKGROUND: In various countries, reports from occupational physicians (OPs) are
      an important source of work-related illness (WRI) data. In Great Britain (GB),
      this is undertaken through the Occupational Physicians Reporting Activity (OPRA)
      surveillance scheme. Because access to an OP is uneven in GB applying the GB
      workforce as the denominator could lead to bias when calculating incidence rates.
      To improve the validity and utility of OP-derived data, it is important to
      improve the quality of the underlying denominator data. AIMS: To estimate the
      proportion of the GB workforce covered by OPRA participants and subsequently to
      calculate OP-derived incidence rates. METHODS: OPRA participants were surveyed
      once in each triennial period (2005-07 and 2008-10) about the workforce they
      covered. Numbers of GB employees within each major industrial division covered by
      the OPRA reporters' occupational health (OH) services were calculated and
      compared with Labour Force Survey data. Incidence rates were calculated for all
      industry and for selected sectors. RESULTS: OPRA reporters' OH services covered
      ~13% of the GB workforce in 2005-07 and 9% in 2008-10. This increased to 34% if
      adjusted to represent all GB OPs. Annual average incidence rates (2005-07 and
      2008-10) were 301 and 336 (total WRI), 150 and 199 (mental ill-health), 103 and
      99 (musculoskeletal), 23 and 24 (skin), and 11 and 9 (respiratory), per 100 000
      employed. CONCLUSIONS: Estimating the workforce covered by OP reporters can
      strengthen the quality of the information source, enabling comparisons between OP
      data and information from other sources, as shown by OPRA in GB.

PMID- 24727563
TI  - Deep vein thrombosis following prolonged kneeling: a case report.
AB  - This report describes a fibreglass mould maker in the yacht building industry who
      developed a deep vein thrombosis (DVT) after 6 weeks of working in a kneeling
      position. We propose that his prolonged kneeling combined with constrictive knee
      pad straps caused vascular compression, precipitating his DVT. A
      hypercoagulability diathesis was suspected but not confirmed. Operator and
      employer education, modified work practices and strapless knee pads are suggested
      as possible preventive measures.

PMID- 24727564
TI  - Cobalt asthma in metalworkers from an automotive engine valve manufacturer.
AB  - BACKGROUND: Cobalt asthma has previously been described in cobalt production
      workers, diamond polishers and glassware manufacturers. AIMS: To describe a case
      series of occupational asthma (OA) due to cobalt, identified at the Birmingham
      Heartlands Occupational Lung Disease Unit, West Midlands, UK. METHODS: Cases of
      cobalt asthma from a West Midlands' manufacturer of automotive engine valves,
      diagnosed between 1996 and 2005, were identified from the SHIELD database of OA.
      Case note data on demographics, employment status, asthma symptoms and diagnostic
      tests, including spirometry, peak expiratory flow (PEF) measurements, skin prick
      testing (SPT) and specific inhalational challenge (SIC) tests to cobalt chloride,
      were gathered, and descriptive statistics used to illustrate the data. RESULTS:
      The natural history of presentations has been described in detail, as well as a
      case study of one of the affected workers. Fourteen metalworkers (86% male; mean
      age 44.9 years) were diagnosed with cobalt asthma between 1996 and 2005. Workers
      were principally stellite grinders, stellite welders or machine setter-operators.
      All workers had positive Occupational Asthma SYStem analyses of serial PEF
      measurements, and sensitization to cobalt chloride was demonstrated in nine
      workers, by SPT or SIC. CONCLUSIONS: We have described a series of 14 workers
      with cobalt asthma from the automotive manufacturing industry, with objective
      evidence for sensitization. Health care workers should remain vigilant for cobalt
      asthma in the automotive manufacturing industry.

PMID- 24727565
TI  - Development and evaluation of an algorithm for computer analysis of maternal
      heart rate during labor.
AB  - BACKGROUND: Maternal heart rate (MHR) recordings are morphologically similar and
      sometimes coincident with fetal heart rate (FHR) recordings and may be useful for
      maternal-fetal monitoring if appropriately interpreted. However, similarly to
      FHR, visual interpretation of MHR features may be poorly reproducible. METHODS: A
      computer algorithm for on-line MHR analysis was developed based on a previously
      existing version for FHR analysis. Inter-observer and computer-observer agreement
      and reliability were assessed in 40 one-hour recordings obtained from 20 women
      during the last 2h of labor. Agreement and reliability were evaluated for the
      detection of basal MHR, long-term variability (LTV), accelerations and
      decelerations, using proportions of agreement (PA) and Kappa statistic (K), with
      95% confidence intervals (95% CI). Changes in MHR characteristics between the
      first and the second hour of the tracings were also evaluated. RESULTS: There was
      a statistically significant inter-observer and computer-observer agreement and
      reliability in estimation of basal MHR, accelerations, decelerations and LTV,
      with PA values ranging from 0.72 (95% CI: 0.62-0.79) to 1.00 (95% CI: 0.99-1.00),
      and K values ranging from 0.44 (95% CI: 0.28-0.60) to 0.89 (95% CI: 0.82-0.96).
      Moreover, basal MHR, number of accelerations and LTV were significantly higher in
      the last hour of labor, when compared to the initial hour. DISCUSSION: The
      developed algorithm for on-line computer analysis of MHR recordings provided good
      to excellent computer-observer agreement and reliability. Moreover, it allowed an
      objective detection of MHR changes associated with labor progression, providing
      more information about the interpretation of maternal-fetal monitoring during
      labor.

PMID- 24727566
TI  - Reply: Congenital mirror movements: lack of decussation of pyramids Mirror
      movement: from physiopathology to treatment perspectives.

PMID- 24727568
TI  - Reply: Thrombolysis in acute ischaemic stroke.

PMID- 24727567
TI  - Deoxynucleoside stress exacerbates the phenotype of a mouse model of
      mitochondrial neurogastrointestinal encephalopathy.
AB  - Balanced pools of deoxyribonucleoside triphosphate precursors are required for
      DNA replication, and alterations of this balance are relevant to human
      mitochondrial diseases including mitochondrial neurogastrointestinal
      encephalopathy. In this disease, autosomal recessive TYMP mutations cause severe
      reductions of thymidine phosphorylase activity; marked elevations of the
      pyrimidine nucleosides thymidine and deoxyuridine in plasma and tissues, and
      somatic multiple deletions, depletion and site-specific point mutations of
      mitochondrial DNA. Thymidine phosphorylase and uridine phosphorylase double
      knockout mice recapitulated several features of these patients including
      thymidine phosphorylase activity deficiency, elevated thymidine and deoxyuridine
      in tissues, mitochondrial DNA depletion, respiratory chain defects and white
      matter changes. However, in contrast to patients with this disease, mutant mice
      showed mitochondrial alterations only in the brain. To test the hypothesis that
      elevated levels of nucleotides cause unbalanced deoxyribonucleoside triphosphate
      pools and, in turn, pathogenic mitochondrial DNA instability, we have stressed
      double knockout mice with exogenous thymidine and deoxyuridine, and assessed
      clinical, neuroradiological, histological, molecular, and biochemical
      consequences. Mutant mice treated with exogenous thymidine and deoxyuridine
      showed reduced survival, body weight, and muscle strength, relative to untreated
      animals. Moreover, in treated mutants, leukoencephalopathy, a hallmark of the
      disease, was enhanced and the small intestine showed a reduction of smooth muscle
      cells and increased fibrosis. Levels of mitochondrial DNA were depleted not only
      in the brain but also in the small intestine, and deoxyribonucleoside
      triphosphate imbalance was observed in the brain. The relative proportion, rather
      than the absolute amount of deoxyribonucleoside triphosphate, was critical for
      mitochondrial DNA maintenance. Thus, our results demonstrate that stress of
      exogenous pyrimidine nucleosides enhances the mitochondrial phenotype of our
      knockout mice. Our mouse studies provide insights into the pathogenic role of
      thymidine and deoxyuridine imbalance in mitochondrial neurogastrointestinal
      encephalopathy and an excellent model to study new therapeutic approaches. 

PMID- 24727569
TI  - Combined suppression of CASP2 and CASP6 protects retinal ganglion cells from
      apoptosis and promotes axon regeneration through CNTF-mediated JAK/STAT
      signalling.
AB  - We have previously shown that crushing the optic nerve induces death of retinal
      ganglion cells by apoptosis, but suppression of CASP2, which is predominantly
      activated in retinal ganglion cells, using a stably modified short interfering
      RNA CASP2, inhibits retinal ganglion cell apoptosis. Here, we report that
      combined delivery of short interfering CASP2 and inhibition of CASP6 using a
      dominant negative CASP6 mutant activates astrocytes and Muller cells, increases
      CNTF levels in the retina and leads to enhanced retinal ganglion cell axon
      regeneration. In dissociated adult rat mixed retinal cultures, dominant negative
      CASP6 mutant + short interfering CASP2 treatment also significantly increases
      GFAP+ glial activation, increases the expression of CNTF in culture, and
      subsequently increases the number of retinal ganglion cells with neurites and the
      mean retinal ganglion cell neurite length. These effects are abrogated by the
      addition of MAB228 (a monoclonal antibody targeted to the gp130 component of the
      CNTF receptor) and AG490 (an inhibitor of the JAK/STAT pathway downstream of CNTF
      signalling). Similarly, in the optic nerve crush injury model, MAB228 and AG490
      neutralizes dominant negative CASP6 mutant + short interfering CASP2-mediated
      retinal ganglion cell axon regeneration, Muller cell activation and CNTF
      production in the retina without affecting retinal ganglion cell survival. We
      therefore conclude that axon regeneration promoted by suppression of CASP2 and
      CASP6 is CNTF-dependent and mediated through the JAK/STAT signalling pathway.
      This study offers insights for the development of effective therapeutics for
      promoting retinal ganglion cell survival and axon regeneration.

PMID- 24727570
TI  - Narcolepsy is a common phenotype in HSAN IE and ADCA-DN.
AB  - We report on the extensive phenotypic characterization of five Italian patients
      from four unrelated families carrying dominant heterozygous DNMT1 mutations
      linked to two distinct autosomal dominant diseases: hereditary sensory and
      autonomic neuropathy with dementia and hearing loss type IE (HSAN IE) and
      autosomal dominant cerebellar ataxia, deafness and narcolepsy (ADCA-DN). Patients
      underwent genetic analysis of DNMT1 gene, neurophysiological tests investigating
      sleep, auditory functions and peripheral nervous system, ophthalmological studies
      including optical coherence tomography, lymphoscintigraphy, brain magnetic
      resonance and nuclear imaging, cerebrospinal fluid hypocretin-1, total tau,
      phosphorylated tau, amyloid-beta1-42 and 14-3-3 proteins measurement, skin,
      muscular and sural nerve biopsies. Exome and direct sequencing studies disclosed
      two different point mutations affecting exon 21 of DNMT1 gene in patients with
      ADCA-DN, a novel heterozygous point mutation in exon 20 in two affected HSAN IE
      siblings, and a trinucleotide deletion in exon 20 in the latter patient with HSAN
      IE. Phenotypic characterization pinpoints that ADCA-DN and HSAN IE represent two
      discrete clinical entities belonging to the same disease spectrum, with variable
      degree of overlap. Remarkably, narcolepsy with or without cataplexy with
      low/intermediate or normal cerebrospinal fluid hypocretin-1 is present in both
      diseases. The human leukocyte antigen DQB1*06:02 was absent in all patients.
      Other common symptoms and features observed in our cases, involving the central
      and peripheral nervous system, include deafness, optic neuropathy-previously not
      reported in HSAN IE-large and small fibres polyneuropathy and lower limbs oedema.
      Overall, the two syndromes share more characteristics than previously recognized
      and narcolepsy is common to both. HSAN IE and ADCA-DN are two extreme phenotypic
      manifestations of a DNMT1 methylopathy. 

PMID- 24727572
TI  - Durability evaluation of biopolymer coating on titanium alloy substrate.
AB  - For this study, a commercially available phosphorylcholine (PC) polymer was
      applied to Ti6Al4V ELI. A multivariate approach to design a statistically
      significant array of experiments was employed to evaluate and estimate
      optimization of PC-immobilization process factors. The seven process factors
      analyzed were (1) power level for RFGD plasma treatment, (2) duration of plasma
      treatment, (3) concentration of PC solution used to coat samples, (4) rate at
      which samples were dipped in/out of the solution, (5) temperature for curing, (6)
      relative humidity level during curing, and (7) duration of curing. Imaging and
      analysis of the coating were done via fluorescence microscopy (FM), confirming
      the uniform coverage of PC polymer on titanium substrate. The process factors
      were evaluated by three measured responses: initial thickness, coating durability
      and degree of cross-linked coating, which were assessed by FM, a spray test and
      extraction in IPA, respectively. Variations in PC solution concentration showed
      no impact on fouling resistance of the resultant coating. It was hypothesized
      that the PC-application process factors could be optimized to yield favorable
      outcomes in durability and degree of cross-linked coating responses. The
      resulting statistical model indicates that PC solution concentration, dip rate,
      and cure temperature are the three greatest singular effects on both durability
      and degree of cross-linking. In addition, plasma treatment of the substrate with
      O2 was effective in enhancing the degree of cross-linking of the polymer surface.

PMID- 24727571
TI  - Mutations in the SPG7 gene cause chronic progressive external ophthalmoplegia
      through disordered mitochondrial DNA maintenance.
AB  - Despite being a canonical presenting feature of mitochondrial disease, the
      genetic basis of progressive external ophthalmoplegia remains unknown in a large
      proportion of patients. Here we show that mutations in SPG7 are a novel cause of
      progressive external ophthalmoplegia associated with multiple mitochondrial DNA
      deletions. After excluding known causes, whole exome sequencing, targeted Sanger
      sequencing and multiplex ligation-dependent probe amplification analysis were
      used to study 68 adult patients with progressive external ophthalmoplegia either
      with or without multiple mitochondrial DNA deletions in skeletal muscle. Nine
      patients (eight probands) were found to carry compound heterozygous SPG7
      mutations, including three novel mutations: two missense mutations c.2221G>A;
      p.(Glu741Lys), c.2224G>A; p.(Asp742Asn), a truncating mutation c.861dupT;
      p.Asn288*, and seven previously reported mutations. We identified a further six
      patients with single heterozygous mutations in SPG7, including two further novel
      mutations: c.184-3C>T (predicted to remove a splice site before exon 2) and
      c.1067C>T; p.(Thr356Met). The clinical phenotype typically developed in mid-adult
      life with either progressive external ophthalmoplegia/ptosis and spastic ataxia,
      or a progressive ataxic disorder. Dysphagia and proximal myopathy were common,
      but urinary symptoms were rare, despite the spasticity. Functional studies
      included transcript analysis, proteomics, mitochondrial network analysis, single
      fibre mitochondrial DNA analysis and deep re-sequencing of mitochondrial DNA.
      SPG7 mutations caused increased mitochondrial biogenesis in patient muscle, and
      mitochondrial fusion in patient fibroblasts associated with the clonal expansion
      of mitochondrial DNA mutations. In conclusion, the SPG7 gene should be screened
      in patients in whom a disorder of mitochondrial DNA maintenance is suspected when
      spastic ataxia is prominent. The complex neurological phenotype is likely a
      result of the clonal expansion of secondary mitochondrial DNA mutations
      modulating the phenotype, driven by compensatory mitochondrial biogenesis. 

PMID- 24727573
TI  - The mechanical properties of the ultra high molecular weight polyethylene grafted
      with 3-dimethy (3-(N-methacryamido) propyl) ammonium propane sulfonate.
AB  - Ultra-high molecular weight polyethylene (UHMWPE) powder was modified with a
      zwitterion monomer with good biocompatibility of MPDSAH (3-dimethy (3-(N
      methacryamido) propyl) ammonium propane sulfonate) by UV irradiation and then hot
      pressed. The microstructure and mechanical properties of modified UHMWPE are
      investigated. The results show that the structure of powder and bulk materials
      has been changed. The modified powders have more filaments than that of
      untreated. The surface of modified bulk materials is more rough and displays the
      granular protuberances which have the random loose arrangement compared with
      untreated UHMWPE. The crystallinity, uniaxial tensile and compressive properties
      decreased after grafting. Ultimate elongations decrease with the increase of the
      monomer concentration and are higher than 300% which is recommended by ASTM and
      ISO except the sample with 0.45mol/L MPDSAH. The friction coefficient of modified
      UHMWPE is lower than that of the untreated UHMWPE and it decreases gradually with
      the increase of monomer concentration. The wear rates have been decreased and the
      wear resistance has been improved under saline and distilled water lubrication. 

PMID- 24727574
TI  - Biomechanical fatigue analysis of an advanced new carbon fiber/flax/epoxy plate
      for bone fracture repair using conventional fatigue tests and thermography.
AB  - The current study is part of an ongoing research program to develop an advanced
      new carbon fiber/flax/epoxy (CF/flax/epoxy) hybrid composite with a "sandwich
      structure" as a substitute for metallic materials for orthopedic long bone
      fracture plate applications. The purpose of this study was to assess the fatigue
      properties of this composite, since cyclic loading is one of the main types of
      loads carried by a femur fracture plate during normal daily activities.
      Conventional fatigue testing, thermographic analysis, and scanning electron
      microscopy (SEM) were used to analyze the damage progress that occurred during
      fatigue loading. Fatigue strength obtained using thermography analysis (51% of
      ultimate tensile strength) was confirmed using the conventional fatigue test (50
      55% of ultimate tensile strength). The dynamic modulus (E(*)) was found to stay
      almost constant at 47GPa versus the number of cycles, which can be related to the
      contribution of both flax/epoxy and CF/epoxy laminae to the stiffness of the
      composite. SEM images showed solid bonding at the CF/epoxy and flax/epoxy
      laminae, with a crack density of only 0.48% for the plate loaded for 2 million
      cycles. The current composite plate showed much higher fatigue strength than the
      main loads experienced by a typical patient during cyclic activities; thus, it
      may be a potential candidate for bone fracture plate applications. Moreover, the
      fatigue strength from thermographic analysis was the same as that obtained by the
      conventional fatigue tests, thus demonstrating its potential use as an alternate
      tool to rapidly evaluate fatigue strength of composite biomaterials. 

PMID- 24727575
TI  - Changes in the spinopelvic parameters of elite weight lifters.
AB  - OBJECTIVE: To describe the changes in the spinopelvic parameters in weight
      lifters and evaluate the factors leading to spinal anatomical changes (eg,
      spondylolysis and listhesis). DESIGN: Case-control study. SETTING: Tertiary,
      institutional. PARTICIPANTS: The study group participants were practicing weight
      lifters in the athletes' village of the 2012 London Olympics. A total of 21 elite
      weight lifters were enrolled. Their data were compared with those of 45 healthy
      volunteers in the control group. INTERVENTIONS: Comparative radiological
      evaluations were performed among the 21 elite weight lifters. Spinopelvic
      parameters (radiographic analysis), including total (TLL), upper (ULL), and lower
      (LLL) lumbar lordoses, sacral slope, pelvic tilt (PT) and incidence, lumbar
      index, and disc angles, were assessed. MAIN OUTCOME MEASURES: The proportional
      ratio of ULL and LLL to TLL (ULL/TLL and LLL/TLL) was measured to describe the
      proportion effect. These values were compared with those of the control group.
      Weight lifters with and those without anatomical changes were subdivided into a
      deformed and nondeformed group, respectively, and further analyzed for
      differences. The correlation between these spinal parameters and the amount and
      duration of weight lifting training was also analyzed. RESULTS: Anatomical
      changes in the lumbar spine were seen in 6 weight lifters (28.6%, P = 0.01). The
      mean TLL, ULL, and LLL values (59.8, 22.6, and 37.2 degrees, respectively) were
      increased, whereas PT (10.3 degrees) was decreased in the athletes compared with
      the volunteers (P = 0.001, 0.005, 0.07, and 0.018, respectively). The ULL/TLL was
      higher in the deformed group than in the nondeformed group (P = 0.036). The
      duration and amount of weight lifting training were not correlated with the
      spinopelvic parameters measured in this study. CONCLUSIONS: The elite weight
      lifters had increased lumbar lordosis and decreased PT compared with the healthy
      volunteers. The ULL/TLL ratio may be used as a predictive marker for lumbar
      deformation.

PMID- 24727576
TI  - Evaluation of a simple test of reaction time for baseline concussion testing in a
      population of high school athletes.
AB  - OBJECTIVE: A common sequela of concussions is impaired reaction time.
      Computerized neurocognitive tests commonly measure reaction time. A simple
      clinical test for reaction time has been studied previously in college athletes;
      whether this test is valid and reliable when assessing younger athletes remains
      unknown. Our study examines the reliability and validity of this test in a
      population of high school athletes. DESIGN: Cross-sectional study. SETTING: Two
      American High Schools. PARTICIPANTS: High school athletes (N = 448) participating
      in American football or soccer during the academic years 2011 to 2012 and 2012 to
      2013. INTERVENTIONS: All study participants completed a computerized baseline
      neurocognitive assessment that included a measure of reaction time (RT comp), in
      addition to a clinical measure of reaction time that assessed how far a standard
      measuring device would fall prior to the athlete catching it (RT clin). MAIN
      OUTCOME MEASURES: Validity was assessed by determining the correlation between RT
      clin and RT comp. Reliability was assessed by measuring the intraclass
      correlation coefficients (ICCs) between the repeated measures of RT clin and RT
      comp taken 1 year apart. RESULTS: In the first year of study, RT clin and RT comp
      were positively but weakly correlated (rs = 0.229, P < 0.001). In the second
      year, there was no significant correlation between RT clin and RT comp (rs =
      0.084, P = 0.084). Both RT clin [ICC = 0.608; 95% confidence interval (CI), 0.434
      0.728] and RT comp (ICC = 0.691; 95% CI, 0.554-0.786) had marginal reliability.
      CONCLUSIONS: In a population of high school athletes, RT clin had poor validity
      when compared with RT comp as a standard. Both RT clin and RT comp had marginal
      test-retest reliability. Before considering the clinical use of RT clin in the
      assessment of sport-related concussions sustained by high school athletes, the
      factors affecting reliability and validity should be investigated further.
      CLINICAL RELEVANCE: Reaction time impairment commonly results from concussion and
      is among the most clinically important measures of the condition. The device
      evaluated in this study has previously been investigated as a reaction time
      measure in college athletes. This study investigates the clinical
      generalizability of the device in a younger population. VIDEO ABSTRACT: A video
      abstract showing how the RT clin device is used in practice is available as
      Supplemental Digital Content 1, http://links.lww.com/JSM/A43.

PMID- 24727577
TI  - Nuclear NF-kappaB contributes to chlorpyrifos-induced apoptosis through p53
      signaling in human neural precursor cells.
AB  - Chlorpyrifos (CPF) is one of the most widely used organophosphate insecticides
      with several harmful effects, including neurotoxicity. Although many studies have
      addressed the neurotoxicity induced by CPF, most data on neurodevelopmental
      damage was obtained from animal models. We are the first group to use human
      neural precursor cells (hNPCs) derived from human embryonic stem cells (hESCs) as
      a developing neuron model to evaluate the mechanisms involved in CPF-induced
      neurotoxicity. CPF was cytotoxic to these cells in a concentration-dependent
      manner, as shown by decreased cell viability and increased lactate dehydrogenase
      release. Furthermore, CPF reduced the expression of AKT and ERK proteins which
      are involved in intracellular survival pathways. Exposure of hNPCs to CPF led to
      the production of reactive oxygen species (ROS), and the antioxidant N-acetyl
      cystein (NAC) attenuated ROS production induced by CPF. In addition, CPF
      increased cytochrome c release into the cytosol and activated caspase-9 and -3,
      indicating that cell death induced by CPF was due to apoptosis in hNPCs.
      Consistent with these findings, CPF treatment reduced the level of Bcl-2 protein
      and increased the level of Bax protein. Especially, CPF increased the
      translocation of BAX into the mitochondria. CPF also induced nuclear accumulation
      of NF-kappaB and p53 proteins in a concentration-dependent manner, and their
      inhibitors attenuated CPF-induced cytotoxicity. In addition, an inhibitor of NF
      kappaB nuclear translocation blocked the increase of p53 in CPF-treated hNPCs.
      These findings show that CPF induced hNPCs death in part through NF-kappaB
      activation via ROS generation, enabling the interaction of p53 with Bcl-2 and Bax
      and subsequent release of cytochrome c. Collectively, these results represent a
      unique molecular characterization of CPF-induced cytotoxicity in hNPCs. These
      data suggest that CPF may affect neurodevelopment in a manner similar to that of
      several known and suspected neurotoxicants. 

PMID- 24727579
TI  - Measuring diaphragm shortening using ultrasonography to predict extubation
      success.

PMID- 24727578
TI  - Loss of pons-to-hypothalamic white matter tracks in brainstem obesity.
AB  - Hyperphagia and obesity have been reported following damage to the hypothalamus
      in humans. Other brain sites are also postulated to be involved in the control of
      food intake and body weight regulation, such as the amygdala and brainstem. The
      brainstem, however, is thought to primarily integrate short-term meal-related
      signals but not affect long-term alterations in body weight, which is controlled
      by higher centers. The objective of this study was to identify structural
      pathways damaged in a patient with a brainstem cavernoma who experienced sudden
      onset of hyperphagia and >50 kg weight gain in <1 year following surgical
      drainage via a midline suboccipital craniotomy. Diffusion tensor imaging revealed
      loss of nerve fiber connections between her brainstem, hypothalamus and higher
      brain centers with preservation of motor tracks. Imaging and endocrine testing
      confirmed normal hypothalamic structure and function. Gastric bypass surgery
      restored normal appetite and body weight to baseline. This is the first report of
      'brainstem obesity' and adds to the brain regions that can determine the long
      term body weight set point in humans.

PMID- 24727582
TI  - Development and validation of a novel algorithm based on the ECG magnet response
      for rapid identification of any unknown pacemaker.
AB  - BACKGROUND: Pacemaker (PM) interrogation requires correct manufacturer
      identification. However, an unidentified PM is a frequent occurrence, requiring
      time-consuming steps to identify the device. OBJECTIVE: The purpose of this study
      was to develop and validate a novel algorithm for PM manufacturer identification,
      using the ECG response to magnet application. METHODS: Data on the magnet
      responses of all recent PM models (<=15 years) from the 5 major manufacturers
      were collected. An algorithm based on the ECG response to magnet application to
      identify the PM manufacturer was subsequently developed. Patients undergoing ECG
      during magnet application in various clinical situations were prospectively
      recruited in 7 centers. The algorithm was applied in the analysis of every ECG by
      a cardiologist blinded to PM information. A second blinded cardiologist analyzed
      a sample of randomly selected ECGs in order to assess the reproducibility of the
      results. RESULTS: A total of 250 ECGs were analyzed during magnet application.
      The algorithm led to the correct single manufacturer choice in 242 ECGs (96.8%),
      whereas 7 (2.8%) could only be narrowed to either 1 of 2 manufacturer
      possibilities. Only 2 (0.4%) incorrect manufacturer identifications occurred. The
      algorithm identified Medtronic and Sorin Group PMs with 100% sensitivity and
      specificity, Biotronik PMs with 100% sensitivity and 99.5% specificity, and St.
      Jude and Boston Scientific PMs with 92% sensitivity and 100% specificity. The
      results were reproducible between the 2 blinded cardiologists with 92% concordant
      findings. CONCLUSION: Unknown PM manufacturers can be accurately identified by
      analyzing the ECG magnet response using this newly developed algorithm.

PMID- 24727583
TI  - What makes the heart rhythm so intricate?

PMID- 24727584
TI  - Lung volume quantified by MRI reflects extracellular-matrix deposition and
      altered pulmonary function in bleomycin models of fibrosis: effects of SOM230.
AB  - Idiopathic pulmonary fibrosis is a progressive and lethal disease, characterized
      by loss of lung elasticity and alveolar surface area, secondary to alveolar
      epithelial cell injury, reactive inflammation, proliferation of fibroblasts, and
      deposition of extracellular matrix. The effects of oropharyngeal aspiration of
      bleomycin in Sprague-Dawley rats and C57BL/6 mice, as well as of intratracheal
      administration of ovalbumin to actively sensitized Brown Norway rats on total
      lung volume as assessed noninvasively by magnetic resonance imaging (MRI) were
      investigated here. Lung injury and volume were quantified by using nongated or
      respiratory-gated MRI acquisitions [ultrashort echo time (UTE) or gradient-echo
      techniques]. Lung function of bleomycin-challenged rats was examined additionally
      using a flexiVent system. Postmortem analyses included histology of collagen and
      hydroxyproline assays. Bleomycin induced an increase of MRI-assessed total lung
      volume, lung dry and wet weights, and hydroxyproline content as well as collagen
      amount. In bleomycin-treated rats, gated MRI showed an increased volume of the
      lung in the inspiratory and expiratory phases of the respiratory cycle and a
      temporary decrease of tidal volume. Decreased dynamic lung compliance was found
      in bleomycin-challenged rats. Bleomycin-induced increase of MRI-detected lung
      volume was consistent with tissue deposition during fibrotic processes resulting
      in decreased lung elasticity, whereas influences by edema or emphysema could be
      excluded. In ovalbumin-challenged rats, total lung volume quantified by MRI
      remained unchanged. The somatostatin analog, SOM230, was shown to have
      therapeutic effects on established bleomycin-induced fibrosis in rats. This work
      suggests MRI-detected total lung volume as readout for tissue-deposition in small
      rodent bleomycin models of pulmonary fibrosis.

PMID- 24727585
TI  - Interaction of caveolin-1 with ATG12-ATG5 system suppresses autophagy in lung
      epithelial cells.
AB  - Autophagy plays a pivotal role in cellular homeostasis and adaptation to adverse
      environments, although the regulation of this process remains incompletely
      understood. We have recently observed that caveolin-1 (Cav-1), a major
      constituent of lipid rafts on plasma membrane, can regulate autophagy in
      cigarette smoking-induced injury of lung epithelium, although the underlying
      molecular mechanisms remain incompletely understood. In the present study we
      found that Cav-1 interacted with and regulated the expression of ATG12-ATG5, an
      ubiquitin-like conjugation system crucial for autophagosome formation, in lung
      epithelial Beas-2B cells. Deletion of Cav-1 increased basal and starvation
      induced levels of ATG12-ATG5 and autophagy. Biochemical analyses revealed that
      Cav-1 interacted with ATG5, ATG12, and their active complex ATG12-ATG5.
      Overexpression of ATG5 or ATG12 increased their interactions with Cav-1, the
      formation of ATG12-ATG5 conjugate, and the subsequent basal levels of autophagy
      but resulted in decreased interactions between Cav-1 and another molecule.
      Knockdown of ATG12 enhanced the ATG5-Cav-1 interaction. Mutation of the Cav-1
      binding motif on ATG12 disrupted their interaction and further augmented
      autophagy. Cav-1 also regulated the expression of ATG16L, another autophagy
      protein associating with the ATG12-ATG5 conjugate during autophagosome formation.
      Altogether these studies clearly demonstrate that Cav-1 competitively interacts
      with the ATG12-ATG5 system to suppress the formation and function of the latter
      in lung epithelial cells, thereby providing new insights into the molecular
      mechanisms by which Cav-1 regulates autophagy and suggesting the important
      function of Cav-1 in certain lung diseases via regulation of autophagy
      homeostasis. 

PMID- 24727586
TI  - Applying metabolomics to uncover novel biology in ARDS.
AB  - A better understanding of the pathogenesis and the resolution of the acute
      respiratory distress syndrome (ARDS) is needed. Although some progress has been
      made with the use of protein biomarkers and candidate gene studies in
      understanding the pathobiology of ARDS, we propose that new studies that measure
      the chemical breakdown products of cellular metabolism (metabolomics) may provide
      new insights into ARDS, in part because metabolomics targets a later point in the
      genomics cascade than is possible with studies of DNA, RNA, and protein
      biomarkers. Technological advances have made large-scale metabolomic profiling
      increasingly feasible. Metabolomic approaches have already achieved novel
      insights in nonpulmonary diseases such as diabetes mellitus and malignancy, as
      well as in sepsis, a major risk factor for developing ARDS. Metabolomic profiling
      is a promising approach to identify novel pathways in both patients at risk for
      developing ARDS as well as in the early phase of established ARDS. 

PMID- 24727587
TI  - Uptake, localization and clearance of quantum dots in ciliated protozoa
      Tetrahymena thermophila.
AB  - Protozoa as phagocytizing cells have been shown to integrate engineered
      nanoparticles (NPs), while the mechanism, dynamics and extent of such uptake are
      unclear. Here our fluorescence microscopy data showed that CdSe/ZnS quantum dots
      (QDs) with primary size of 12 nm were readily phagocytized into the food vacuoles
      of Tetrahymena thermophila in a time- and dose-dependent manner. Twenty hours
      after the exposure to QDs in sublethal concentration the clearance of the QDs
      from the cells was incomplete suggesting that phagocytosis of QDs into food
      vacuoles was not the only pathway of uptake by T. thermophila. This was further
      proven by the results that the inhibition of phagocytosis did not block the
      internalization of QDs into protozoans. This study provides a new insight into
      uptake and cellular trafficking of subtoxic concentrations of nanoparticles that
      may, due to prolonged retention times in the cells, pose risks by potentially
      becoming available to higher trophic levels. 

PMID- 24727588
TI  - Spatial variability of methane: attributing atmospheric concentrations to
      emissions.
AB  - Atmospheric methane concentrations were quantified along transects in
      Switzerland, using a mobile laser spectrometer combined with a GPS, to identify
      their spatio-temporal patterns and their controlling factors. Based on these
      measurements in complex terrain dominated by agriculture, three main factors were
      found to be responsible for the diurnal and regional patterns of atmospheric
      methane: (1) magnitude and distribution of methane sources within the region, (2)
      efficiency of vertical exchange, and (3) local wind patterns within the complex
      topography. An autocorrelation analysis of measured methane concentrations showed
      that nighttime measurements close to the ground provide information about
      regional sources (up to 8.3 km), while daytime measurements only carry
      information about sources located up to 240 m away in the upwind fetch. Compared
      to daytime concentrations, nighttime methane concentrations do also better
      reflect emissions obtained from a spatially explicit methane emission inventory
      and allowed the investigation of inconsistencies in this emission inventory. 

PMID- 24727590
TI  - Chemosignalling, mechanotransduction and ciliary behaviour in the embryonic node:
      Computational evaluation of competing theories.
AB  - Precise specification of left-right asymmetry is essential for patterning the
      internal organs of vertebrates. Within the embryonic node, posteriorly polarised
      cilia rotate, causing a leftward fluid flow (nodal flow) that establishes left
      right asymmetry. The mechanism by which an embryo senses nodal flow remains
      uncertain. Existing hypotheses argue that either nodal flow carries morphogen(s)
      or lipid-bounded vesicles towards the left, thereby generating an asymmetric
      signal, and/or that mechano-sensory cilia sense this unidirectional flow,
      stimulating left-sided intracellular calcium signalling. To date, direct and
      definitive evidence supporting these hypotheses has been lacking. In this study,
      we conduct a multi-scale study to simulate the nodal cilia and the fluidic
      environment, analysing left-right signal transmission. By employing computational
      simulation techniques and solving the relevant three-dimensional unsteady
      transport equations, we study the flow pattern produced by the rotation of active
      cilia. By importing dilute species and particles into the computational domain,
      we investigate the transport of morphogens and nodal vesicular parcels,
      respectively. Furthermore, by extending the analysis to include the solid
      mechanics of passive deformable cilia and the coupling of their structural
      behaviour with the emerging fluid mechanics, we study the response of passive
      cilia to the nodal flow. Our results reproduce the unidirectional nodal flow,
      allowing us to evaluate the plausibility of both chemo- and mechano-sensing
      hypotheses. The quantitative measurements of the flow rate, the molecular
      transport and distribution provide guidance regarding the necessary morphogen
      molecular weights to break signalling symmetry. The passive sensory ciliary
      deformation gives indications regarding the plausibility of this mechano
      signalling mechanism.

PMID- 24727591
TI  - Assessing asymmetry using reflection and rotoinversion in biomedical engineering
      applications.
AB  - Symmetry is a trait that has been extensively reviewed, especially clinically, as
      an indication of ideal geometry and health. Many geometric symmetry assessment
      techniques rely on two-dimensional measurements that do not account for the three
      dimensional nature of the object. In this article, two methods, reflection and a
      process termed rotoinversion, a combination of reflection and rotation, are
      presented as potential methods to assess an object's deviation from symmetry.
      With reflection, the geometric models are reflected about a calculated best plane
      of symmetry. With rotoinversion, the models are reflected about an arbitrary
      plane and then rigidly translated and rotated to best align the translated and
      original models. The methods give the same results for bilaterally symmetric
      objects, but different results for bilaterally and rotationally symmetric
      objects. The two methods are applied to assess asymmetry in adolescent idiopathic
      scoliosis torso geometric models, producing similar results. There was an angle
      of 0.408 degrees  between the normal to the plane of reflection from the
      reflection process and the normal from the rotoinversion process and average
      rotation of 0.067 degrees  from rotoinversion. The most appropriate method
      depends on the purpose of the symmetry assessment and must be determined on a
      case-by-case basis.

PMID- 24727589
TI  - Transcriptional regulation of seprase in invasive melanoma cells by transforming
      growth factor-beta signaling.
AB  - The tumor invasive phenotype driven by seprase expression/activity has been
      widely examined in an array of malignant tumor cell types; however, very little
      is known about the transcriptional regulation of this critical protease. Seprase
      (also named fibroblast activation protein-alpha, antiplasmin-cleaving enzyme, and
      dipeptidyl prolyl peptidase 5) is expressed at high levels by stromal fibroblast,
      endothelial, and tumor cells in a variety of invasive tumors but is undetectable
      in the majority of normal adult tissues. To examine the transcriptional
      regulation of the gene, we cloned the human seprase promoter and demonstrated
      that endogenous seprase expression and exogenous seprase promoter activity are
      high in invasive melanoma cells but not in non-invasive melanoma cells/primary
      melanocytes. In addition, we identified a crucial TGF-beta-responsive cis
      regulatory element in the proximal seprase promoter region that enabled robust
      transcriptional activation of the gene. Treatment of metastatic but not
      normal/non-invasive cells with TGF-beta1 caused a rapid and profound up
      regulation of endogenous seprase mRNA, which coincided with an abolishment of the
      negative regulator c-Ski, and an increase in binding of Smad3/4 to the seprase
      promoter in vivo. Blocking TGF-beta signaling in invasive melanoma cells through
      overexpression of c-Ski, chemically using SB-431542, or with a neutralizing
      antibody against TGF-beta significantly reduced seprase mRNA levels. Strikingly,
      RNAi of seprase in invasive cells greatly diminished their invasive potential in
      vitro as did blocking TGF-beta signaling using SB-431542. Altogether, we found
      that seprase is transcriptionally up-regulated in invasive melanoma cells via the
      canonical TGF-beta signaling pathway, supporting the roles of both TGF-beta and
      seprase in tumor invasion and metastasis. 

PMID- 24727592
TI  - Unified quantification of variation in passive knee joint constraint.
AB  - The interrelationship that exists between multiple degrees of freedom to produce
      a net constraint across the range of passive motion of the knee is not fully
      understood. Manual joint laxity assessments were performed on 28 cadaveric
      specimens and used to develop a unified description of the passive laxity
      envelope that incorporated multiple degrees of freedom into a single analysis
      using radial basis functions. The unified envelopes were then included in a
      principal component analysis to identify the primary modes of variation. The
      first three modes of variation constituted 82% of the variation. The first
      principal component (36.5% explained variation) correlated with changes to the
      relationship between varus-valgus and internal-external rotation and had the
      largest impact on internal-external laxity. The second principal component (27.2%
      explained variation) correlated with a shift in the internal-external envelope.
      The third principal component (18.3% explained variation) correlated with a shift
      in the varus-valgus envelope and a change in varus-valgus laxity. This research
      presents a novel methodology for quantifying complex changes to passive knee
      constraint, which may be used as a means for objectively scoring joint laxity and
      evaluating complex relationships between degrees of freedom in a single analysis.

PMID- 24727593
TI  - Proteasome-mediated quality control of S-nitrosylated mitochondrial proteins.
AB  - Accumulating low level mitochondrial insults are thought to be key to aging
      processes and neurodegeneration. Among other stressors, protein damage due to
      nitrosative stress negatively impacts mitochondrial function and is linked to
      neurodegeneration. Using biotin switch technique, we show that mitochondrial
      proteins are S-nitrosylated not only in the presence but also in the absence of
      exogenous nitrosative stress. In addition, we revealed a role for the ubiquitin
      proteasome system and the outer mitochondrial membrane associated degradation
      (OMMAD)-component p97 in the quality control of S-nitrosylated mitochondrial.
      Taken together, constant proteasome-mediated clearance of nitrosatively-damaged
      proteins from mitochondria is likely important for maintaining organelle
      function. 

PMID- 24727594
TI  - Mitochondrial biogenesis in plants during seed germination.
AB  - Mitochondria occupy a central role in the eukaryotic cell. In addition to being
      major sources of cellular energy, mitochondria are also involved in a diverse
      range of functions including signalling, the synthesis of many essential organic
      compounds and a role in programmed cell death. The active proliferation and
      differentiation of mitochondria is termed mitochondrial biogenesis and
      necessitates the coordinated communication of mitochondrial status within an
      integrated cellular network. Two models of mitochondrial biogenesis have been
      defined previously, the growth and division model and the maturation model. The
      former describes the growth and division of pre-existing mature organelles
      through a form of binary fission, while the latter describes the propagation of
      mitochondria from structurally and biochemically simple promitochondrial
      structures that upon appropriate stimuli, mature into fully functional
      mitochondria. In the last decade, a number of studies have utilised seed
      germination in plants as a platform for the examination of the processes
      occurring during mitochondrial biogenesis. These studies have revealed many new
      aspects of the tightly regulated procession of events that define mitochondrial
      biogenesis during this period of rapid development. A model for mitochondrial
      biogenesis that supports the maturation of mitochondria from promitochondrial
      structures has emerged, where mitochondrial signalling plays a crucial role in
      the early steps of seed germination. 

PMID- 24727595
TI  - Physical exercise prevents and mitigates non-alcoholic steatohepatitis-induced
      liver mitochondrial structural and bioenergetics impairments.
AB  - Exercise is considered a non-pharmacological tool against several lifestyle
      disorders in which mitochondrial dysfunction is involved. The present study aimed
      to analyze the preventive (voluntary physical activity-VPA) and therapeutic
      (endurance training-ET) role of exercise against non-alcoholic steatohepatitis
      (NASH)-induced liver mitochondrial dysfunction. Sixty male Sprague-Dawley rats
      were divided into standard-diet sedentary (SS, n=20), standard-diet VPA (SVPA,
      n=10), high-fat diet sedentary (HS, n=20) and high-fat diet VPA (HVPA, n=10).
      After 9weeks of diet-treatment, half of SS and HS animals were engaged in an ET
      program (SET and HET) for 8weeks, 5days/week and 60min/day. Liver mitochondrial
      oxygen consumption and transmembrane-electric potential (DeltaPsi) were evaluated
      in the presence of glutamate-malate (G/M), palmitoyl-malate (P/M) and succinate
      (S/R). Mitochondrial enzymes activity, lipid and protein oxidation, oxidative
      phosphorylation (OXPHOS) subunits, cytochrome c, adenine nucleotide translocator
      (ANT) and uncoupling protein-2 (UCP2) content were assessed. HS groups show the
      histological features of NASH in parallel with decreased DeltaPsi and respiratory
      control (RCR) and ADP/O ratios (G/M and P/M). A state 3 decrease (G/M and S/R),
      FCCP-induced uncoupling respiration (S/R) and ANT content were also observed.
      Both exercise types counteracted oxygen consumption (RCR, ADP/O and FCCP
      uncoupling state) impairments and improved DeltaPsi (lag-phase). In conclusion,
      exercise prevented or reverted (VPA and ET, respectively) the bioenergetic
      impairment induced by NASH, but only ET positively remodeled NASH-induced liver
      structural damage and abnormal mitochondria. It is possible that alterations in
      inner membrane integrity and fatty acid oxidation may be related to the observed
      phenotypes induced by exercise. 

PMID- 24727596
TI  - Association between hypoglycemia and the type of insulin in diabetic patients
      treated with multiple injections: an observational study.
AB  - INTRODUCTION: Hypoglycemia may have serious health consequences; therefore, it is
      important to expand knowledge on the factors that increase its prevalence.
      OBJECTIVES: The aim of the study was to evaluate the effect of the type of
      insulin-human vs. analogue-on the incidence of mild and severe hypoglycemia, body
      weight, and hemoglobin A1c (HbA1c) levels. PATIENTS AND METHODS: A total of 203
      diabetic patients treated with intensive insulin therapy completed the
      questionnaire on hypoglycemia at baseline and at 3 and 6 months of the follow-up.
      Body weight and HbA1c levels were measured at baseline and at 6 months. Incidence
      of mild and severe hypoglycemia, body weight, and HbA1c levels were compared
      between patients treated with short-acting analogue and those treated with short
      acting human insulin (regardless of the type of long-acting insulin used) and
      between patients receiving short- and long-acting analogue insulin and those
      receiving short- and long-acting human insulin. A multiple logistic regression
      analysis was used to find independent risk factors of severe hypoglycemia.
      RESULTS: At baseline, mild hypoglycemia was more common in patients receiving
      insulin analogue. There were no differences between the subgroups in the
      incidence of severe hypoglycemia, HbA1c levels, and body weight. Male sex, older
      age, and the dose of long-acting insulin were independently associated with a
      higher incidence of severe hypoglycemia. Type 2 diabetes and higher body weight
      were associated with a lower risk of severe hypoglycemia. CONCLUSIONS: Our
      results suggest that use of insulin analogues may predispose to more frequent
      episodes of mild hypoglycemia, but it does not increase the incidence of severe
      hypoglycemia in patients on intensive insulin therapy. Insulin analogues are not
      different from human insulin in terms of the effects on HbA1c levels and body
      mass.

PMID- 24727597
TI  - Importance of heterogeneous aggregation for NP fate in natural and engineered
      systems.
AB  - The growing interest in nanoparticles (NP) is inevitably translating into an
      increase of their emissions in the environment. On the other hand, the necessary
      knowledge about the fate and transport of these NPs in the environment remains
      limited. In particular it is critically important to understand how the
      interactions of NPs with the particles already present in environmental matrices
      affect their fate, transport, and eventually persistence in the environment. In
      this study we present a computer model that expands upon the existing simple
      homogeneous aggregation models to account for heterogeneous aggregation between
      NPs and the distribution of natural particles already present in environmental
      waters. The model follows the concentrations of purely nanoparticle aggregates,
      purely background particles aggregates, and mixed aggregates, as well as the
      composition of mixed aggregates. After analytical evaluation, we ran simulations
      to illustrate the complexity of heterogeneous aggregation and its impact on the
      fate of NPs. The model predicts that the impact of NP size on their persistence
      in the environment is accentuated for low affinity between NPs and background
      particles, and for low background particle concentration. 

PMID- 24727598
TI  - Future trends in soil cadmium concentration under current cadmium fluxes to
      European agricultural soils.
AB  - The gradual increase of soil cadmium concentrations in European soils during the
      20th century has prompted environmental legislation to limit soil cadmium (Cd)
      accumulation. Mass balances (input-output) reflecting the period 1980-1995
      predicted larger Cd inputs via phosphate (P) fertilizers and atmospheric
      deposition than outputs via crop uptake and leaching. This study updates the Cd
      mass balance for the agricultural top soils of EU-27+Norway (EU-27+1). Over the
      past 15 years, the use of P fertilizers in the EU-27+1 has decreased by 40%. The
      current mean atmospheric deposition of Cd in EU is 0.35 g Cd ha(-1) yr(-1), this
      is strikingly smaller than values used in the previous EU mass balances (~3 g Cd
      ha(-1) yr(-1)). Leaching of Cd was estimated with most recent data of soil
      solution Cd concentrations in 151 soils, which cover the range of European soil
      properties. No significant time trends were found in the data of net applications
      of Cd via manure, compost, sludge and lime, all being small sources of Cd at a
      large scale. Modelling of the future long-term changes in soil Cd concentrations
      in agricultural top soils under cereal or potato culture predicts soil Cd
      concentrations to decrease by 15% over the next 100 years in an average scenario,
      with decreasing trends in some scenarios being more prevalent than increasing
      trends in other scenarios. These Cd balances have reverted from the general
      positive balances estimated 10 or more years ago. Uncertainty analysis suggests
      that leaching is the most uncertain relative to other fluxes.

PMID- 24727599
TI  - Front gardens to car parks: changes in garden permeability and effects on flood
      regulation.
AB  - This study addresses the consequences of widespread conversion of permeable front
      gardens to hard standing car parking surfaces, and the potential consequences in
      high-risk urban flooding hotspots, in the city of Southampton. The last two
      decades has seen a trend for domestic front gardens in urban areas to be
      converted for parking, driven by the lack of space and increased car ownership.
      Despite media and political attention, the effects of this change are unknown,
      but increased and more intense rainfall, potentially linked to climate change,
      could generate negative consequences as runoff from impermeable surfaces
      increases. Information is limited on garden permeability change, despite the
      consequences for ecosystem services, especially flood regulation. We focused on
      eight flooding hotspots identified by the local council as part of a wider urban
      flooding policy response. Aerial photographs from 1991, 2004 and 2011 were used
      to estimate changes in surface cover and to analyse permeability change within a
      digital surface model in a GIS environment. The 1, 30 and 100 year required
      attenuation storage volumes were estimated, which are the temporary storage
      required to reduce the peak flow rate given surface permeability. Within our
      study areas, impermeable cover in domestic front gardens increased by 22.47% over
      the 20-year study period (1991-2011) and required attenuation storage volumes
      increased by 26.23% on average. These increases suggest that a consequence of the
      conversion of gardens to parking areas will be a potential increase in flooding
      frequency and severity - a situation which is likely to occur in urban locations
      worldwide.

PMID- 24727600
TI  - Silicon nanograss based impedance biosensor for label free detection of rare
      metastatic cells among primary cancerous colon cells, suitable for more accurate
      cancer staging.
AB  - Detection of rare metastatic cells within a benign tumor is a key challenge to
      diagnose the cancerous stage of the patients tested by clinical human biopsy or
      pap smear samples. We have fabricated and tested a nanograssed silicon based
      bioelectronic device with the ability of detecting a few human colon invasive
      cancer cells (SW48) in a mixed cell culture of primary cancerous colon cells
      (HT29) without any biochemical labels. A discernible impedance change was
      elicited after the presence of 5% metastatic cells in the whole benign sample.
      The electric field penetration as well as current flow to metastatic cells is
      different from benign ones due to their different membrane dielectric parameters.
      Beta dispersion as one of intrinsic bioelectrical properties of the cell membrane
      in blocking the stimulating current flow in the range of kHz is the specific
      parameter involved in our diagnosis approach. It can reflect in-depth information
      about the dielectric properties and the pathological condition of a cell before
      and after metastatic transformation. Electrically active doped silicon nanograss
      structures owing to their superior nanocontacts with cell membrane can detect any
      slight variations in current being originated from the presence of rare
      metastatic cells on the surface of the sensing electrode. The experimental
      results revealed that bare doped silicon microelectrodes are incapable of
      resolving different grades of attached cells.

PMID- 24727601
TI  - Electrochemical evaluation of troponin T imprinted polymer receptor.
AB  - The selective detection and quantification of macromolecular targets is a
      fundamental biological mechanism in nature. Molecularly imprinted polymers (MIPs)
      have been identified as one of the most promising synthetic alternatives to
      bioreceptors. However, expanding this methodology towards selective recognition
      of bulky templates such as proteins appears to be extremely challenging due to
      problems associated with removal of the template from the polymeric network. In
      this study, polymer imprinted with troponin T (TnT) was assessed using
      electrochemical methods and the influence of various extraction methods,
      including conventional immersion extraction, thermal annealing and ultrasonic
      assisted extraction, on the binding characteristics of the troponin-to-imprinted
      polymer receptor was elucidated. Cyclic voltammetric deposition of o
      phenylenediamine (o-PD) film in the presence of TnT as a template was performed
      in acetate buffer (0.5 M, pH 5.2) on a gold substrate. Solvent extraction of the
      target molecule was optimised and followed by subsequent washing with water. The
      electrochemistry of a ferro/ferricyanide probe was used to characterise the TnT
      MIP receptor film. The incubation of the TnT MIP receptor-modified electrode with
      respect to TnT concentration resulted in a suppression of the ferro/ferricyanide
      redox current. The dissociation constant (KD) was calculated using a two-site
      model of template affinity for the TnT MIP receptor. The synthetic TnT MIP
      receptor had high affinity for TnT with a KD of 2.3*10(-13) M.

PMID- 24727602
TI  - Facile and rapid generation of 3D chemical gradients within hydrogels for high
      throughput drug screening applications.
AB  - We propose a novel application of dielectrophoresis (DEP) to make three
      dimensional (3D) methacrylated gelatin (GelMA) hydrogels with gradients of micro-
      and nanoparticles. DEP forces were able to manipulate micro- and nanoparticles of
      different sizes and materials (i.e., C2C12 myoblasts, polystyrene beads, gold
      microparticles, and carbon nanotubes) within GelMA hydrogels in a rapid and
      facile way and create 3D gradients of these particles in a microchamber.
      Immobilization of drugs, such as fluorescein isothiocyanate-dextran (FITC
      dextran) and 6-hydroxydopamine (6-OHDA), on gold microparticles allowed us to
      investigate the high-throughput release of these drugs from GelMA-gold
      microparticle gradient systems. The latter gradient constructs were incubated
      with C2C12 myoblasts for 24h to examine the cell viability through the release of
      6-OHDA. The drug was released from the microparticles in a gradient manner,
      inducing a cell viability gradient. This novel approach to create 3D chemical
      gradients within hydrogels is scalable to any arbitrary length scale. It is
      useful for making anisotropic biomimetic materials and high-throughput platforms
      to investigate cell-microenvironment interactions in a rapid, simple, cost
      effective, and reproducible manner. 

PMID- 24727603
TI  - Membrane assembly of the functional KcsA potassium channel in a vesicle-based
      eukaryotic cell-free translation system.
AB  - The potassium channel KcsA was heterologously expressed in a eukaryotic cell-free
      system. Both, the expression yields and functional analysis of the protein were
      reported. Qualitative and quantitative analyses of KcsA expression were performed
      by using (14)C-labeled leucine as one of the amino acids supplemented in the cell
      free reaction mixture. There was a time dependent increase in the protein yield
      as well as the intensity of the native tetramer band in insect cell derived
      microsomes. Electrophysiology measurements demonstrated the functional activity
      of the microsomes harboring KcsA showing single-channel currents with the typical
      biophysical characteristics of the ion channel. The channel behavior was
      asymmetric and showed positive rectification with larger currents towards
      positive voltages. KcsA channel currents were effectively blocked by potassium
      selective barium (Ba(2+)). This functional demonstration of an ion channel in
      eukaryotic cell-free system has a large potential for future applications
      including drug screening, diagnostic applications and functional assessment of
      complex membrane proteins like GPCRs by coupling them to ion channels in cell
      free systems. Furthermore, membrane proteins can be expressed directly from
      linear DNA templates within 90 min, eliminating the need for additional cloning
      steps, which makes this cell-free system fast and efficient.

PMID- 24727604
TI  - Biofuel cell for generating power from methanol substrate using alcohol oxidase
      bioanode and air-breathed laccase biocathode.
AB  - We report here an alcohol oxidase (AOx) based third generation bioanode for
      generating power from methanol substrate in a fuel cell setup using air breathed
      laccase biocathode. A composite three dimensional microporous matrix containing
      multiwalled carbon nanotubes, carbon paste and nafion was used as electroactive
      support for immobilization of the enzymes on toray carbon paper as supporting
      electrode in the fabrication of the bioelectrodes. Polyethylenimine was used to
      electrostatically stabilize the AOx (pI 4.3) on the anode operating on direct
      electrochemistry principle. Osmium tetroxide on poly (4-vinylpyridine) was used
      to wire the laccase for electron transfer in the biocathode. The enzymatic
      biofuel cell (EFC) generated an open circuit potential of 0.61 (+/-0.02) V with a
      maximum power density of 46 (+/-0.002) uW cm(-2) at an optimum of 1M methanol, 25
      degrees C and an internal resistance of 0.024 uOmega. The operation and storage
      half life (t1/2) of the EFC were 17.22 h and 52 days, respectively at a fixed
      load of 1.85 Omega. The findings have demonstrated the feasibility of developing
      EFC using AOx based bioanode and laccase based biocathode without applying any
      toxic free mediator and metal electrode supports for generating electricity.

PMID- 24727606
TI  - Flower-like ZnO nanostructure based electrochemical DNA biosensor for bacterial
      meningitis detection.
AB  - Zinc oxide (ZnO) nanostructures possessing flower-like morphology have been
      synthesised onto platinized silicon substrate by simple and economical
      hydrothermal method. The interaction of physically immobilized single stranded
      thiolated DNA (ss th-DNA) probe of N. meningitides onto the nanostructured ZnO
      (ZNF) matrix surface have been investigated using cyclic voltammetry (CV) and
      electrochemical impeadance spectroscopy (EIS). The electrochemical sensing
      response behaviour of the DNA bioelectrode (ss th-DNA/ZNF/Pt/Si) has been studied
      by both differential pulse voltammetric (DPV) as well as impedimetric techniques.
      The fabricated DNA biosensor can quantify wide range of the complementary target
      ss th-DNA in the range 5-240 ng MUl(-1) with good linearity (R=0.98), high
      sensitivity (168.64 MUA ng(-1) MUl cm(-2)) and low detection limit of about 5 ng
      MUl(-1). Results emphasise that the fabricated flower-like ZnO nanostructures
      offer a useful platform for the immobilization of DNA molecules and could be
      exploited for efficient detection of complementary target single stranded DNA
      corresponding to N. meningitides.

PMID- 24727605
TI  - Real-time analysis of the effects of toxic, therapeutic and sub-therapeutic
      concentrations of digitoxin on lung cancer cells.
AB  - Digitoxin belongs to a naturally occurring class of cardiac glycosides (CG);
      digitoxin is clinically approved for heart failure and known for its anti-cancer
      effects against non-small lung cancer cells (NSCLC). However, concerns associated
      with its narrow therapeutic index and its concentration-dependent mechanism of
      action are rising. Thus, before digitoxin implementation in designing and
      developing safer and more effective CG-based anti-cancer therapies, its
      pharmacological and safety profiles need to be fully elucidated. In this research
      we used a combinatorial approach to evaluate the anti-cancer mechanisms of
      digitoxin in real-time. Our approach employed a non-invasive electric cell
      impedance sensing technique as a proxy to monitor NSCLC behavior post-exposure to
      toxic, therapeutic and sub-therapeutic concentrations of the drug. By developing
      structure-function combinatorial relations we showed that digitoxin targets
      cancer cells in a time and dose-dependant manner by activating pro-apoptotic and
      anti-proliferative signaling cascades that results in strengthening cellular
      adhesion and sequestration of key regulatory proliferation protein from the
      nucleus. 

PMID- 24727607
TI  - Bioplasmonic calligraphy for multiplexed label-free biodetection.
AB  - Printable multi-marker biochips that enable simultaneous quantitative detection
      of multiple target biomarkers in point-of-care and resource-limited settings are
      a holy grail in the field of biodiagnostics. However, preserving the
      functionality of biomolecules, which are routinely employed as recognition
      elements, during conventional printing approaches remains challenging. In this
      article, we introduce a simple yet powerful approach, namely plasmonic
      calligraphy, for realizing multiplexed label-free bioassays. Plasmonic
      calligraphy involves a regular ballpoint pen filled with biofunctionalized gold
      nanorods as plasmonic ink for creating isolated test domains on paper substrates.
      Biofriendly plasmonic calligraphy approach serves as a facile method to
      miniaturize the test domain size to few mm(2), which significantly improves the
      sensitivity of the plasmonic biosensor compared to bioplasmonic paper fabricated
      using immersion approach. Furthermore, plasmonic calligraphy also serves as a
      simple and efficient means to isolate multiple test domains on a single test
      strip, which facilitates multiplexed biodetection and multi-marker biochips.
      Plasmonic calligraphy, which can be potentially automated by implementing with a
      robotic arm, serves as an alternate path forward to overcome the limitations of
      conventional ink-jet printing. 

PMID- 24727608
TI  - Dithiothreitol-capped fluorescent gold nanoclusters: an efficient probe for
      detection of copper(II) ions in aqueous solution.
AB  - We report here a Green method for the synthesis of fluorescent gold nanoclusters
      using dithiothreitol (DTT) as both a capping agent and reducing agent at 22 
      degrees C and pH 8. The physical and chemical properties of the synthesized
      AuNCs@DTT were studied by TEM and UV-vis absorption, fluorescence, and X-ray
      photoelectron spectroscopy. AuNCs@DTT recognizes cupric ions with high
      selectivity and sensitivity, which allows this material to act as a copper(II)
      sensor in aqueous solution. A linear relationship was observed between the
      fluorescence intensity of the DTT capped gold nanoclusters and the concentration
      of copper(II) ions, in the range of 0-60 MUM with a detection limit of 80 nM. The
      copper content in serum was also analyzed by using this copper sensor. It was
      shown that data obtained using the proposed method was comparable to values
      obtained by the traditional colorimetric method. This technique represents an
      alternative method for the determination of serum copper in clinical diagnosis
      especially for those laboratories which lack expensive analytical facilities.

PMID- 24727609
TI  - High loading Pt nanoparticles on functionalization of carbon nanotubes for
      fabricating nonenzyme hydrogen peroxide sensor.
AB  - A very efficient, simple approach was developed to fabricate a high Pt
      nanoparticles-loading multiwall carbon nanotube (MWCNTs) amperometric sensor for
      hydrogen peroxide (H2O2) determination. In this strategy, MWCNTs were first
      functionalized with an anionic surfactant, sodium dodecyl sulfate (SDS); then the
      Pt nanoparticles (NPs) were loaded on MWCNTs-SDS by electrodepositing. The large
      amounts of Pt nanoparticles could be well deposited on the surface of the MWCNTs
      SDS modified electrode, as revealed by scanning electron microscopy (SEM). In
      addition, the PtNPs/MWCNTs-SDS composite was also characterized by
      electrochemical methods including cyclic voltammetry (CV) and electrochemical
      impedance spectroscopy (EIS). The experimental results demonstrated that the
      constructed electrode exhibited good catalytic activity toward the hydrogen
      peroxide, and obtained a wide linear range from 5.8*10(-9) to 1.1*10(-3) M with a
      limit of detection (LOD) of 1.9*10(-9) M, which was superior to that obtained
      with other H2O2 electrochemical sensors reported previously. Moreover, it can
      also be applied to real samples analysis. The excellent performance of hydrogen
      peroxide sensor was ascribed to the MWCNTs-SDS composites being used as effective
      load matrix for the deposition of PtNPs and the synergistic amplification effect
      of the two kinds of nanomaterials-PtNPs and MWCNTs.

PMID- 24727610
TI  - Osmotic parameters of red blood cells from umbilical cord blood.
AB  - The transfusion of red blood cells from umbilical cord blood (cord RBCs) is
      gathering significant interest for the treatment of fetal and neonatal anemia,
      due to its high content of fetal hemoglobin as well as numerous other potential
      benefits to fetuses and neonates. However, in order to establish a stable supply
      of cord RBCs for clinical use, a cryopreservation method must be developed. This,
      in turn, requires knowledge of the osmotic parameters of cord RBCs. Thus, the
      objective of this study was to characterize the osmotic parameters of cord RBCs:
      osmotically inactive fraction (b), hydraulic conductivity (Lp), permeability to
      cryoprotectant glycerol (Pglycerol), and corresponding Arrhenius activation
      energies (Ea). For Lp and Pglycerol determination, RBCs were analyzed using a
      stopped-flow system to monitor osmotically-induced RBC volume changes via
      intrinsic RBC hemoglobin fluorescence. Lp and Pglycerol were characterized at 4
      degrees C, 20 degrees C, and 35 degrees C using Jacobs and Stewart equations with
      the Ea calculated from the Arrhenius plot. Results indicate that cord RBCs have a
      larger osmotically inactive fraction compared to adult RBCs. Hydraulic
      conductivity and osmotic permeability to glycerol of cord RBCs differed compared
      to those of adult RBCs with the differences dependent on experimental conditions,
      such as temperature and osmolality. Compared to adult RBCs, cord RBCs had a
      higher Ea for Lp and a lower Ea for Pglycerol. This information regarding osmotic
      parameters will be used in future work to develop a protocol for cryopreserving
      cord RBCs.

PMID- 24727611
TI  - Medetomidine suppresses cardiac and gastric sympathetic nerve activities but
      selectively activates cardiac vagus nerve.
AB  - BACKGROUND: To identify a pharmacological agent that can selectively activate
      cardiac vagus nerve for potential use in vagal activation therapy against heart
      failure, the effects of medetomidine on autonomic nerve activities in both the
      heart and stomach were examined. METHODS AND RESULTS: In anesthetized rabbits,
      microdialysis probes were implanted into both the right atrial and gastric walls.
      Dialysate acetylcholine (ACh) and norepinephrine (NE) concentrations were
      measured by high-performance liquid chromatography. First, the effects of
      100MUg/kg of intravenous medetomidine on vagal ACh and sympathetic NE releases
      were examined. Medetomidine significantly increased cardiac ACh release (4.7+/
      1.1 to 7.8+/-0.9nmol/L, P<0.05), but suppressed gastric ACh release (8.0+/-2.6 to
      3.5+/-1.5nmol/L, P<0.01). In contrast, medetomidine suppressed both cardiac and
      gastric NE releases. Second, the effects of medetomidine on ACh releases induced
      by electrical vagus nerve stimulation (VNS; 10Hz) were examined. Electrical VNS
      significantly increased both cardiac (6.7+/-1.2 to 14.8+/-1.8nmol/L, P<0.01) and
      gastric (3.8+/-0.8 to 181.3+/-65.6nmol/L, P<0.01) ACh releases. Medetomidine did
      not alter the VNS-induced increases in ACh release. CONCLUSIONS: Medetomidine
      suppresses both cardiac and gastric sympathetic nerve activities. In contrast,
      medetomidine activates cardiac vagus nerve but inhibits gastric vagal activity.
      Medetomidine might be one of the potential pharmacological agents for vagal
      activation therapy against heart failure without the risk of gastric adverse
      effects.

PMID- 24727612
TI  - The present and future of fractional flow reserve.
AB  - Revascularization of coronary artery stenosis should be based on objective
      evidence of ischemia. Fractional flow reserve (FFR) is an invasive physiologic
      index that can be easily measured in the cardiac catheterization laboratory to
      assess the functional significance of coronary stenosis. FFR-guided
      revascularization strategy has been proven to be better than angiography-guided
      strategy in patients with coronary artery disease. Recent development of more
      convenient ways to induce hyperemia will reduce the barrier to measuring FFR and
      further expand its clinical applicability. Invasive physiologic indices without
      hyperemia are also under active investigation. Moreover, a novel noninvasive FFR
      measurement based on coronary CT angiography and computational fluid dynamics has
      been developed and will soon be incorporated into clinical practice. Given the
      rapid adoption of invasive and noninvasive physiologic indices in daily practice,
      a review of the current status of FFR and future perspectives is presented.

PMID- 24727613
TI  - Catheter ablation for atrial fibrillation in the real world--insights from the J
      CARAF registry.

PMID- 24727614
TI  - Protein tyrosine phosphatase PTPN9 regulates erythroid cell development through
      STAT3 dephosphorylation in zebrafish.
AB  - Protein tyrosine phosphatases (PTPs) are involved in hematopoiesis, but the
      function of many PTPs is not well characterized in vivo. Here, we have identified
      Ptpn9a, an ortholog of human PTPN9, as a crucial regulator of erythroid cell
      development in zebrafish embryos. ptpn9a, but not ptpn9b, was expressed in the
      posterior lateral plate mesoderm and intermediate cell mass - two primitive
      hematopoietic sites during zebrafish embryogenesis. Morpholino-mediated knockdown
      of ptpn9a caused erythrocytes to be depleted by inhibiting erythroid cell
      maturation without affecting erythroid proliferation and apoptosis. Consistently,
      both dominant-negative PTPN9 (with mutation C515S) and siRNA against PTPN9
      inhibited erythroid differentiation in human K562 cells. Mechanistically,
      depletion of ptpn9 in zebrafish embryos in vivo or in K562 cells in vitro
      increased phosphorylated STAT3, and the hyper-phosphorylated STAT3 entrapped and
      prevented the transcription factors GATA1 and ZBP-89 (also known as ZNF148) from
      regulating erythroid gene expression. These findings imply that PTPN9 plays an
      important role in erythropoiesis by disrupting an inhibitory complex of
      phosphorylated STAT3, GATA1 and ZBP-89, providing new cellular and molecular
      insights into the role of ptpn9a in developmental hematopoiesis. 

PMID- 24727616
TI  - The Medical Council of India: need for a total overhaul.

PMID- 24727617
TI  - The prevention of Parent-to-child Transmission Programme: is it fair to women?

PMID- 24727615
TI  - Loss of p27 upregulates MnSOD in a STAT3-dependent manner, disrupts intracellular
      redox activity and enhances cell migration.
AB  - Cell migration is a dynamic process that is central to a variety of physiological
      functions as well as disease pathogenesis. The modulation of cell migration by
      p27 (officially known as CDKN1B) has been reported, but the exact mechanism(s)
      whereby p27 interacts with downstream effectors that control cell migration have
      not been elucidated. By systematically comparing p27(+/+) mouse embryonic
      fibroblasts (MEFs) with genetically ablated p27(-/-) MEFs using wound-healing,
      transwell and time-lapse microscopic analyses, we provide direct evidence that
      p27 inhibits both directional and random cell migration. Identical results were
      obtained with normal and cancer epithelial cells using complementary knockdown
      and overexpression approaches. Additional studies revealed that overexpression of
      manganese superoxide dismutase (MnSOD, officially known as SOD2) and reduced
      intracellular oxidation played a key role in increased cell migration in p27
      deficient cells. Furthermore, we identified signal transducer and activator of
      transcription 3 (STAT3) as the transcription factor responsible for p27-regulated
      MnSOD expression, which was further mediated by ERK- and ATF1-dependent
      transactivation of the cAMP response element (CRE) within the Stat3 promoter.
      Collectively, our data strongly indicate that p27 plays a crucial negative role
      in cell migration by inhibiting MnSOD expression in a STAT3-dependent manner. 

PMID- 24727618
TI  - Ethical challenges in biobanking: moving the agenda forward in India.
AB  - There is no agreement on the typology and definition of biobanks.The present
      regulations across countries, including India, focus ongenomic and genetic
      databases and DNA and cell line biobanking.It is unclear how the range of the
      holdings of biological samples in diagnostic and research laboratories fall under
      these regulatory frameworks. Biobank-related research has become very attractive
      because of advances in sample storage and data processing, a better understanding
      of the human genome, and high throughput laboratory assays. There is extensive
      literature and much debate on the subject, especially on the ethical and
      regulatory dilemmas, in the developed countries, but this is hardly the casein
      developing countries. This paper is based on a review of the published documents
      and data, and aims at evaluating the ethical frameworks for biobanking in the
      Indian context. The issues of"'broad consent; commercialisation of samples, and
      extended sample use are discussed. The governance of biobanks emerges as an
      integral part of the ethical responsibilities of institutions. It also makes the
      implementation of national guidelines possible, and helps to enhance the trust
      and confidence of local contributors in biobank research.

PMID- 24727619
TI  - Unmodified electroconvulsive therapy: a false dilemma.
AB  - A recent statement commissioned by the Indian Association of Private Psychiatry
      recommends that unmodified electroconvulsive therapy (ECT) should still be used
      in some settings in India, invoking the principle of beneficence. This paper
      critically analyses the IAPP statement in terms of both scientific accuracy and
      ethical principles. It is found that the statement falls short of the ethical
      principles of beneficence, non-maleficence and justice. It is the duty of
      psychiatrists and psychiatric associations to offer the best available care to
      their patients, both on scientific and ethical grounds. 

PMID- 24727620
TI  - A degree in bioethics: an "introspective" analysis from Pakistan.
AB  - The success of degree-level bioethics programmes, a recent development across the
      world, is generally evaluated on the basis of their quantifiable impact; for
      instance, the number of publications graduates produce. The author conducted a
      study of Pakistani graduates who had pursued a higher qualification in bioethics,
      and on the basis of the respondents' written and verbal narratives, this paper
      presents an analysis of their perceptions of the internal impact of bioethics
      degree programmes. Using these narratives, the paper also analyses the reactions
      of their colleagues to their new qualification.The respondents reported
      significant changes in their thinking and actions following their education in
      bioethics. They exhibited more empathy towards their patients and research
      subjects, and became better "listeners~ They also reported changes in
      practices,the most significant being the discontinuation of the linkages they had
      established with pharmaceutical firms to seek support,because of concerns related
      to conflict of interest. Although some respondents believed that their new
      qualification was generally welcomed by their colleagues, who considered them
      aesthetics resources, others reported that their colleagues harboured
      unreasonable and impractical expectations from them, and that these were
      impossible to fulfil. They also got the feeling of being ostracized and regarded
      as "ethics watchdogs~ Whereas the internalisation of bioethics is an encouraging
      finding in this cohort, the mixed reception that bioethics and those involved in
      it received indicates a Jack of understanding of the field and is a source of
      concern.

PMID- 24727621
TI  - Knowledge, attitudes and practices related to healthcare ethics among medical and
      dental postgraduate students in south India.
AB  - BACKGROUND: Conventional medical training offers students little help in
      resolving the ethical dilemmas they will encounter as healthcare professionals.
      OBJECTIVE: This article aims to assess the knowledge of, practices in and
      attitudes to healthcare ethics among postgraduate medical and dental students.
      METHODOLOGY: A questionnaire-based, cross-sectional study was carried out at two
      medical and dental schools in south India. A total of 209 medical and dental
      students were contacted and at least three were selected from each subspecialty
      of medicine and dentistry.One hundred and ninety-nine consented to participate
      and 7 72 returned the questionnaire (response rate 83%). The questionnaire,which
      was a 35-item pre-tested, self-administered questionnaire,included both closed
      and open-ended questions. The proposal for the study was approved by the
      institutional review board (IRB)and the permission of the respective heads of
      department was obtained. Written consent was obtained from each participant.The
      returned questionnaires were analysed using SPSS version 7 7 .5. Descriptive
      analysis was carried out for all the data. The attitudes of the postgraduates of
      different courses towards practical ethical problems were compared using a Chi
      square test. RESULTS: Medical and dental postgraduates had obtained their
      knowledge of bioethics from "other sources such as the Internet,newspapers, etc~
      followed by their "undergraduate training" and"experience at work': Nearly 68% of
      the postgraduates had not undergone any bioethics training. Nearly 98% of the
      medical postgraduates, as compared to 79% of the dental postgraduates,knew that
      their institution had an ethics committee. There was a difference between the
      medical and dental students in terms of their attitude to and knowledge of
      healthcare ethics, with the former having a superior knowledge of the subject and
      a better attitude. CONCLUSIONS: The medical and dental postgraduates come across
      ethical issues during their training, but are not equipped to resolve the ethical
      dilemmas they encounter. The dental postgraduates have less of an appreciation of
      healthcare ethics than their medical counterparts. The incorporation of a
      bioethics curriculum in the initial period of the postgraduate programme would be
      beneficial.

PMID- 24727622
TI  - Publication misconduct among medical professionals in India.
AB  - This study was planned as an exploratory study to determine the extent of
      occurrence of misconduct in publication (gift-authorship,ghost-authorship,
      falsification of data, fabrication of data,plagiarism, and duplication) amongst
      biomedical researchers.It was a questionnaire-based study, conducted at 9
      institutions;6 medical colleges (4 government-run and 2 private), 7 non teaching
      government hospital, and 2 corporate hospitals, located in northern, central and
      southern India. The study was conducted between August 2072 and March 2073. 755
      senior residents (<3 years after post-graduation) and young faculty members (< 70
      years after post-graduation) with at least five previous publications were
      administered a structured questionnaire, in which no identifying information was
      collected. In addition to personal characteristics, the information collected
      included their knowledge of publication ethics, their opinions about the
      prevalence of these practices among their colleagues, and details of any first
      hand information on publication misconduct. 7 55 responses were included for
      analysis. 7 4 7 (9 7 %) respondents agreed that they had some knowledge of
      publication ethics; but only 29% believed it was adequate. The most commonly
      observed misconduct was offering gift authorship, reported by 707 (65%); followed
      by alteration of data reported by 88 (56%). Plagiarism was observed by 83
      respondents (53%); while 52 (33.5%) respondents had observed a colleague's name
      being omitted from a paper to which she/he had significantly contributed. A
      majority of respondents in the present study reported witnessing publication
      misconduct,thereby revealing the common occurrence of this problem among Indian
      biomedical researchers.

PMID- 24727623
TI  - Identifying beneficiaries for user fee waivers: ethical challenges in public
      health.

PMID- 24727624
TI  - Corruption in healthcare: a problem in Germany, too.

PMID- 24727625
TI  - Professional misconduct or criminal negligence: when does the balance tilt?

PMID- 24727626
TI  - The 10th Brazilian Congress on Bioethics.

PMID- 24727627
TI  - Hysterectomy and other "hard" software (sensitive) questions.

PMID- 24727628
TI  - How Hindi films tarnish the image of psychiatrists.

PMID- 24727629
TI  - Organ donation: awareness a must.

PMID- 24727630
TI  - Scientific sanctions: a catastrophe for the civilized world.

PMID- 24727631
TI  - How anchoring proteins shape pain.
AB  - Cellular responsiveness to external stimuli can be altered by extracellular
      mediators which activate membrane receptors, in turn signalling to the
      intracellular space via calcium, cyclic nucleotides, membrane lipids or enzyme
      activity. These signalling events trigger a cascade leading to an effector which
      can be a channel, an enzyme or a transcription factor. The effectiveness of these
      intracellular events is enhanced when they are maintained in close proximity by
      anchoring proteins, which assemble complexes of signalling molecules such as
      kinases together with their targets, and in this way enhance both the speed and
      the precision of intracellular signalling. The A kinase anchoring protein (AKAP)
      family are adaptor proteins originally named for their ability to associate
      Protein Kinase A and its targets, but several other enzymes bound by AKAPs have
      now been found and a wide variety of target structures has been described. This
      review provides an overview of anchoring proteins involved in pain signalling.
      The key anchoring proteins and their ion channel targets in primary sensory
      neurons responding to painful stimuli (nociceptors) are discussed. 

PMID- 24727632
TI  - Mechanistic elements and critical factors of cellular reprogramming revealed by
      stepwise global gene expression analyses.
AB  - A better understanding of the cellular and molecular mechanisms involved in the
      reprogramming of somatic cells is essential for further improvement of induced
      pluripotent stem (iPS) cell technology. In this study, we enriched for cells
      actively undergoing reprogramming at different time points by sorting the cells
      stained with a stem cell-selective fluorescent chemical probe CDy1 for their
      global gene expression analysis. Day-to-day comparison of differentially
      expressed genes showed highly dynamic and transient gene expressions during
      reprogramming, which were largely distinct from those of fully-reprogrammed
      cells. An unbiased analysis of functional regulation indicated robust modulation
      of concurrent programs at critical junctures. Globally, transcriptional programs
      involved in cell proliferation, morphology and signal transduction were instantly
      triggered as early as 3 days-post-infection to prepare the cell for reprogramming
      but became somewhat muted in the final iPS cells. On the other hand, the highly
      coordinated metabolic reprogramming process was more gradually activated.
      Subsequent network analysis of differentially expressed genes indicated PDGF-BB
      as a core player in reprogramming which was verified by our gain- and loss-of
      function experiments. As such, our study has revealed previously-unknown insights
      into the mechanisms of cellular reprogramming.

PMID- 24727633
TI  - Corneal wound healing promoted by 3 blood derivatives: an in vitro and in vivo
      comparative study.
AB  - PURPOSE: The aim of this study was to compare the effect on corneal wound healing
      of 3 differently manufactured blood derivatives [autologous serum (AS), platelet
      rich plasma, and serum derived from plasma rich in growth factors (s-PRGF)].
      METHODS: Scratch wound-healing assays were performed on rabbit primary corneal
      epithelial cultures and human corneal epithelial cells. Additionally, mechanical
      debridement of rabbit corneal epithelium was performed. Wound-healing progression
      was assessed by measuring the denuded areas remaining over time after treatment
      with each of the 3 blood derivatives or a control treatment. RESULTS: In vitro
      data show statistically significant differences in the healing process with all
      the derivatives compared with the control, but 2 of them (AS and s-PRGF) induced
      markedly faster wound healing. In contrast, although the mean time required to
      complete in vivo reepithelization was similar to that of AS and s-PRGF treatment,
      only wounds treated with s-PRGF were significantly smaller in size from 2.5 days
      onward with respect to the control treatment. CONCLUSIONS: All 3 blood
      derivatives studied are promoters of corneal reepithelization. However, the
      corneal wound-healing progresses differently with each derivative, being faster
      in vitro under AS and s-PRGF treatment and producing in vivo the greatest
      decrease in wound size under s-PRGF treatment. These findings highlight that the
      manufacturing process of the blood derivatives may modulate the efficacy of the
      final product.

PMID- 24727634
TI  - Phenotypic heterogeneity of corneal endothelium in iridocorneal endothelial
      syndrome by in vivo confocal microscopy.
AB  - PURPOSE: To present a case of iridocorneal endothelial (ICE) syndrome showing
      phenotypic heterogeneity of endothelial morphology between the 2 eyes of a
      patient as visualized by in vivo confocal microscopy (IVCM). METHODS: Confocal
      microscopy using the Heidelberg Retina Tomograph (HRT)-3 with Rostock Cornea
      Module was performed bilaterally during routine follow-up on a 60-year-old lady
      being managed as a case of ICE syndrome with secondary glaucoma in the right eye.
      RESULTS: IVCM revealed endothelial changes in both eyes, which however varied in
      morphology. Endothelium of the right eye showed a "total ICE" pattern with "ICE
      type of cells," that is, diffuse involvement with enlarged, pleomorphic
      "epithelioid" cells having hyper-reflective nuclei and no intervening areas of
      the normal endothelium. The left endothelium had broad areas of normal hexagonal
      endothelial mosaic interspersed with different types of ICE cells showing nipple
      shaped evaginations, light dark reversal and central craters with hyper
      reflective rims. CONCLUSIONS: This report with the help of IVCM demonstrates that
      though ICE syndrome is a clinical entity which classically has been considered
      predominantly unilateral, the endothelial changes can be bilateral and
      heterogeneous. The apparent heterogeneity in the present case may represent 2
      different stages of the disease process at the level of the corneal endothelium
      advanced disease OD and presymptomatic disease OS.

PMID- 24727635
TI  - Algorithm for the estimation of the corneal power in eyes with previous myopic
      laser refractive surgery.

PMID- 24727636
TI  - CorneaJ: an imageJ Plugin for semi-automated measurement of corneal endothelial
      cell viability.
AB  - PURPOSE: A reliable experimental measurement of endothelial cell (EC) viability
      is paramount in the assessment of new drugs, devices, and surgical processes
      liable to damage the corneal endothelium, as well as during endothelial
      bioengineering. We previously used triple Hoechst-Ethidium-Calcein-AM labeling
      coupled with image analysis to determine the viability and mortality of ECs on
      the whole cornea, thus defining the new notion of viable EC density. To make it
      accessible to all, and for improved reproducibility, we have now developed an
      ImageJ plugin with improved thresholding algorithms. METHODS: The CorneaJ plugin
      comprised contrast improvement, regional selection of pixels with similar gray
      levels, simplified thresholding facilitated by a user-friendly images display,
      and the option of manual touch-up to increase accuracy. After Hoechst-Ethidium
      Calcein-AM labeling, the endothelium of 10 human corneas was observed with a
      fluorescent microscope with motorized stage. The performance of CorneaJ was
      compared with standard manual thresholding: accuracy was determined by comparison
      with fully manual selection of viable ECs by an expert; and reproducibility, by
      calculating the intraclass coefficient and coefficient of variation (100 *
      SD/mean) of 7 independent observers. RESULTS: CorneaJ was more accurate than the
      standard thresholding, with a deviation from the expected value of -1.8% [95%
      confidence interval (CI), -2.7 to -0.9] versus 6.0% (95% CI, 2.8-9.3),
      respectively, P < 0.001. It was also more reproducible, with an intraclass
      coefficient of 0.98 (95% CI, 0.954-0.994) versus 0.81 (95% CI, 0.628-0.937) and a
      mean coefficient of variation of 2.6 (1.4-7.4) and 5.7 (3.4-19.8), P = 0.005.
      CONCLUSIONS: CorneaJ is a new, fast, and reproducible free image analysis tool
      that could help standardize experimental measurement of corneal EC viability.

PMID- 24727637
TI  - Dry eye predisposes to corneal neovascularization and lymphangiogenesis after
      corneal injury in a murine model.
AB  - PURPOSE: Dry eye disease is becoming recognized as an immune-inflammation
      mediated disorder. Surgical insults such as corneal incision or suture can
      aggravate dry eye. We sought to determine whether underlying dry eye aggravates
      corneal inflammatory infiltration, hemangiogenesis, and lymphangiogenesis (LY)
      induced by surgical injury in a murine model. METHODS: We used treatment arms;
      one, normal eye (non-dry eye) and the other, a scopolamine-induced dry eye model.
      We first compared the corneas of both groups on which no surgery was performed
      with confocal and fluorescent microscopy. In subgroups of each treatment arm, we
      made a corneal incision followed by 2 corneal sutures to approximate the wound.
      After harvesting the cornea on postoperative day 9 and immunohistochemical
      staining, we compared corneal neovascularization (NV), LY, and CD11b inflammatory
      cell infiltration between non-dry eye and dry eye groups. RESULTS: In corneas in
      which no surgery was performed, the dry eye group showed more CD11b cell
      infiltration than did the non-dry eye group (P < 0.05). With respect to corneas
      after injury, there was significantly more hemangiogenesis, LY, and inflammatory
      infiltration in the dry eye group than in the non-dry eye group (all P < 0.05).
      CONCLUSIONS: The underlying status of the cornea, whether it is dry or not, plays
      a significant role in the development of NV, LY, and inflammation after corneal
      injury. Dry eye can aggravate post-injury NV, LY, and inflammation.

PMID- 24727638
TI  - Keratoconus and age association: a possible age cohort effect.

PMID- 24727639
TI  - Decline of ambient air pollution levels due to measures to control automobile
      emissions and effects on the prevalence of respiratory and allergic disorders
      among children in Japan.
AB  - BACKGROUND: In Japan, air pollution due to nitrogen oxides (NOx) and particulate
      matter (PM) has been gradually reduced since control measures based on the
      Automobile NOx/PM law were enforced beginning in 2001. The effects of decrease in
      air pollutants due to the control measures during the past decade on the
      prevalence of respiratory and allergic disorders such as asthma in children were
      evaluated. METHODS: Using data of 618,973 children collected in 28 regions of
      Japan from 1997 to 2009, we evaluated whether reductions in the concentrations of
      nitrogen dioxide (NO2) and suspended particulate matter (SPM) contribute to the
      decrease in the prevalence of asthma, wheezing, bronchitis, allergic rhinitis,
      and atopic dermatitis by multiple linear regression analysis, including
      adjustments for related factors. RESULTS: The annual rates of decrease in air
      pollution in the PM-law-enforced areas were 2.0 and 2.5 times higher for NO2 and
      SPM, respectively, compared with those in the non-enforced areas. The prevalence
      of asthma decreased significantly at -0.073% per year in the areas in which
      measures based on the Automobile NOx/PM law were taken but not in area where such
      measures were not applied. Multiple linear regression analysis showed a reduction
      in the ambient air pollution was significantly associated with a reduction in the
      prevalence of asthma, with a rate of 0.118% [95% confidence interval (CI): 0.012
      0.225] per 1 ppb for NO2, and 0.050% [95% CI: 0.020-0.080] per 1 MUg/m(3) for
      SPM. An increase in the ambient air pollution was associated with an increase in
      the prevalence of atopic dermatitis of 0.390% [95% CI: 0.107-0.673] per 1 ppb for
      NO2, 0.141% [95% CI: 0.058-0.224] per 1 MUg/m(3) for SPM. The changes in the
      prevalence of wheezing and allergic rhinitis were not significantly correlated
      with changes in air pollutant concentrations. CONCLUSIONS: The enforcement of
      measures to control automobile emissions based on the Automobile NOx/PM law was
      shown to have reduced air pollution and contributed to decreases in the
      prevalence of respiratory and allergic disorders in 3-year-old children.

PMID- 24727640
TI  - Heavy metals in fish from the Aleutians: interspecific and locational
      differences.
AB  - The objectives of this study were to examine levels of arsenic, cadmium, lead,
      mercury and selenium in edible tissue of seven species of marine fish collected
      from several Aleutian islands (in 2004) to determine: (1) interspecific
      differences, (2) locational differences (among Aleutian Islands), (3) size
      related differences in any metal levels within a species, and (4) potential risk
      to the fish or to predators on the fish, including humans. We also compared
      metals levels to those of three other fish species previously examined in detail,
      as well as examining metals in the edible tissue of octopus (Octopus dofleini).
      Octopus did not have the highest levels of any metal. There were significant
      interspecific differences in all metal levels among the fish species, although
      the differences were less than an order of magnitude, except for arsenic (mean of
      19,500 ppb in Flathead sole, Hippoglossoides elassodon). Significant intraisland
      variation occurred among the four sites on Amchitka, but there was not a
      consistent pattern. There were significant interisland differences for some
      metals and species. Mercury levels increased significantly with size for several
      species; lead increased significantly for only one fish species; and cadmium and
      selenium decreased significantly with size for halibut (Hippoglossus stenolepis).
      The Alaskan Department of Health and Social Services supports unrestricted
      consumption of most Alaskan fish species for all people, including pregnant
      women. Most mean metal concentrations were well below the levels known to
      adversely affect the fish themselves, or predators that consume them (including
      humans), except for mercury in three fish species (mean levels just below 0.3
      ppm), and arsenic in two fish species. However, even at low mercury levels,
      people who consume fish almost daily will exceed guideline values from the
      Centers for Disease Control and the Environmental Protection Agency.

PMID- 24727641
TI  - Drought as a mental health exposure.
AB  - The mental health impact of drought is poorly quantified and no previous research
      has demonstrated a relationship between distress and explicit environmentally
      based measures of drought. With continuing climate change, it is important to
      understand what drought is and how it may affect the mental health. We quantified
      drought in terms of duration and intensity of relative dryness and identified
      drought characteristics associated with poor mental health to evaluate any
      vulnerability in rural and urban communities. Our methods involved analysis of
      100-year longitudinal records of monthly rainfall linked to one wave (2007-2008)
      of the Household, Income and Labour Dynamics in Australia Survey. Cluster
      analysis was used to characterise different patterns of dryness and linear
      regression analysis was used to examine associations with participant distress,
      as well as the moderating role of rural locality. The results showed that, during
      a seven-year period of major and widespread drought, one pattern of relative
      dryness (extreme cumulative number of months in drought culminating in a recent
      period of dryness lasting a year or more) was associated with increased distress
      for rural but not urban dwellers. The increase in distress was estimated to be
      6.22%, based on 95% confidence intervals. Thus, we show that it is possible to
      quantitatively identify an association between patterns of drought and distress. 

PMID- 24727642
TI  - Hazard identification of the potential for dieldrin carcinogenicity to humans.
AB  - Although dieldrin's use in the U.S. was partially banned in the 1970s and its use
      was completely eliminated in 1987, dieldrin continues to be a common contaminant
      at hazardous waste sites. The USEPA's current cancer potency estimate for
      dieldrin was derived in 1987 and is based on the production of mouse liver
      tumors. Because of its environmental persistence and its relatively high USEPA
      cancer potency estimate, dieldrin functions as a cleanup "driver" in many
      hazardous site remediations. Since 1987, new risk assessment perspectives and new
      data on dieldrin's carcinogenic potential have arisen. This review presents a
      reassessment of dielrin's human cancer potential in light of these new data and
      new perspectives. Based on this reassessment, dieldrin may be carcinogenic
      through multiple modes of action. These modes of action may operate within the
      same tissue, or may be specific to individual tissues. Of the several possible
      carcinogenic modes of action for dieldrin, one or more may be more relevant to
      human cancer risk than others, but the relative importance of each is unknown. In
      addition, neither the details of the possible modes of action, nor the shape of
      the tumor dose-response curves associated with each are sufficiently well known
      to permit quantitative cancer dose-response modeling. Thus, the mouse liver tumor
      data used by the USEPA in its 1987 assessment remain the only quantitative data
      available for cancer dose-response modeling. 

PMID- 24727643
TI  - Visual mental imagery in psychopathology--implications for the maintenance and
      treatment of depression.
AB  - Negative mental images are a common feature in a range of mental disorders as
      well as in healthy subjects. Intrusive negative mental images have only recently
      become a focus of attention in clinical research on depression. Research so far
      indicates that they can be an important factor regarding the onset and chronicity
      of affective disorders. This article is the first to provide an extensive
      overview of the current state of research in the field of visual mental images in
      depression. It aims to investigate disorder-specific characteristics, as well as
      the role of imagery as a maintaining factor. A detailed definition and
      description of empirical results about mental images in depressive disorders is
      followed by a presentation and analysis of treatment studies using imagery
      techniques in depressed samples. Additionally, methodological issues like small
      sample sizes and the lack of control groups are pointed out and implications for
      future research are discussed. Case vignettes are included in the appendix to
      exemplify the importance of negative mental images in patients suffering from
      depression. 

PMID- 24727644
TI  - Tabanids: neglected subjects of research, but important vectors of disease
      agents!
AB  - Tabanids are nuisance pests for people and livestock because of their painful and
      irritating bite, persistent biting behavior, and blood ingestion. About 4400
      tabanid species have been described; they are seasonally present in all kinds of
      landscapes, latitudes, and altitudes. High populations have a significant
      economic impact on outdoor activities, tourism, and livestock production.
      Tabanids are also vectors of animal disease agents, including viruses, bacteria
      and parasites. However, tabanids have received little attention in comparison
      with other hematophagous Diptera. Here, we highlight the many direct and indirect
      impacts of tabanids and provide a brief summary of tabanid morphology, biology,
      and life cycle. Impacts include pathogen transmission, parasite transportation
      (Dermatobia hominis), biological transmission (Loa loa), and mechanical
      transmission of viruses, such as equine infectious anemia virus, protozoa, such
      as Trypanosoma evansi and Besnotia besnoiti, and bacteria, such as Bacillus
      anthracis and Anaplasma marginale. We discuss parameters of mechanical
      transmission and its mathematical modeling. Control methods for tabanid
      populations are also summarized; these include trapping, the use of insecticides,
      repellents, and livestock protection. Lastly recommendations are provided for the
      direction of future research. 

PMID- 24727645
TI  - Trypanosoma cruzi: Genome characterization of phosphatidylinositol kinase gene
      family (PIK and PIK-related) and identification of a novel PIK gene.
AB  - Chagas disease is caused by the protozoan Trypanosoma cruzi which affects 10
      million people worldwide. Very few kinases have been characterized in this
      parasite, including the phosphatidylinositol kinases (PIKs) that are at the heart
      of one of the major pathways of intracellular signal transduction. Recently, we
      have classified the PIK family in T. cruzi using five different models based on
      the presence of PIK conserved domains. In this study, we have mapped PIK genes to
      the chromosomes of two different T. cruzi lineages (G and CL Brener) and
      determined the cellular localization of two PIK members. The kinases have crucial
      roles in metabolism and are assumed to be conserved throughout evolution. For
      this reason, they should display a conserved localization within the same
      eukaryotic species. In spite of this, there is an extensive polymorphism
      regarding PIK localization at both genomic and cellular levels, among different
      T. cruzi isolates and between T. cruzi and Trypanosomabrucei, respectively. We
      showed in this study that the cellular localization of two PIK-related proteins
      (TOR1 and 2) in the T. cruzi lineage is distinct from that previously observed in
      T. brucei. In addition, we identified a new PIK gene with peculiar feature, that
      is, it codes for a FYVE domain at N-terminal position. FYVE-PIK genes are
      phylogenetically distant from the groups containing exclusively the FYVE or PIK
      domain. The FYVE-PIK architecture is only present in trypanosomatids and in virus
      such as Acanthamoeba mimivirus, suggesting a horizontal acquisition. Our Bayesian
      phylogenetic inference supports this hypothesis. The exact functions of this FYVE
      PIK gene are unknown, but the presence of FYVE domain suggests a role in
      membranous compartments, such as endosome. Taken together, the data presented
      here strengthen the possibility that trypanosomatids are characterized by
      extensive genomic plasticity that may be considered in designing drugs and
      vaccines for prevention of Chagas disease. 

PMID- 24727646
TI  - Comparison of a quantitative Real-Time PCR assay and droplet digital PCR for copy
      number analysis of the CCL4L genes.
AB  - The controversy surrounding the findings that copy number variation, of the CCL3
      encoding genes, influences HIV-1 infection and disease progression has been in
      part attributed to the variable results obtained from methods used for copy
      number evaluation. Like CCL3, the genes encoding the CC chemokine CCL4, also a
      natural ligand of the CCR5 receptor, are found to occur in population-specific
      multiple copy number and have been shown to play a protective role against HIV-1.
      This study evaluated the standard method of quantitative Real-Time PCR (qPCR) and
      droplet digital PCR (ddPCR) for CCL4L gene copy number determination. The CCL4
      encoding genes are CCL4, occurring in two copies per diploid genome (pdg), and
      the non-allelic CCL4L genes, comprised of CCL4L1 and CCL4L2, which are both found
      in multiple copies pdg. Copy number of CCL4L, CCL4L1 and CCL4L2 was determined in
      a cohort of HIV-1-uninfected individuals from the South African Black (n=23) and
      Caucasian (n=32) population groups using qPCR and ddPCR. A stronger correlation
      between the number of CCL4L copies and the sum of CCL4L1 and CCL4L2 copies
      generated by ddPCR (r=0.99, p<0.0001) compared to qPCR (r=0.87, p<0.0001) was
      observed. Real-Time qPCR exhibited greater inaccuracy at higher copy numbers
      which is particularly relevant to our cohort of Black individuals who have a
      higher range of CCL4L copies (3-6) compared to Caucasians (0-4) and a higher
      population median (4 and 2, respectively). Medians and ranges of CCL4L1 (Black:
      2, 0-4, Caucasian: 0, 0-2) and CCL4L2 (Black: 2, 1-5, Caucasian: 2, 0-3) were
      also higher in the Black population. Droplet digital PCR was shown to be a far
      superior method to qPCR for assessment of CCL4 gene copy number variation, the
      accuracy of which is essential for studies of the contribution of variable gene
      copy number to phenotypic outcomes of host infection and disease course. 

PMID- 24727647
TI  - Effects of niacin on Staphylococcus aureus internalization into bovine mammary
      epithelial cells by modulating NF-kappaB activation.
AB  - Niacin is a precursor of coenzymes NAD and NADP and plays a critical role in
      electron transfer during the metabolic process. In addition to its nutrimental
      function, niacin has long been used for the treatment of lipid disorders and
      cardiovascular disease. However, the effect of niacin on Staphylococcus aureus
      (S. aureus) internalization into bovine mammary epithelial cells (bMEC) remains
      unclear. Here we sought to examine the effect of niacin on S. aureus
      internalization into bovine mammary epithelial cells (bMEC) and to investigate
      the potential mechanism. In this study, the growth of S. aureus supplemented with
      niacin (0.5-2 mM) was monitored turbidimetrically at 600 nm for 24 h and cell
      viability was measured by MTT assay. Gentamicin protection assay was carried out
      to determine the effect of niacin on S. aureus internalization into bMEC. To
      determine the potential mechanism, tracheal antimicrobial peptide (TAP) and beta
      defensin (BNBD5) expressions were detected by quantitative real-time polymerase
      chain reaction (qRT-PCR). The activation of nuclear factor-kappa B (NF-kappaB)
      was determined by Western blotting. The results showed that niacin (0.5-2 mM) did
      not affect S. aureus growth and bMEC viability, whereas it inhibits S. aureus
      internalization ranging from 13% to 42% and down-regulated the mRNA expression of
      TAP and BNBD5 compared to the control group. No exactly relationship was
      discovered between S. aureus internalization into bMEC and antimicrobial peptide
      expression, while niacin inhibited S. aureus-induced NF-kappaB activation in a
      dose manner. These dates suggest that inhibiting NF-kappaB activation may be the
      potential mechanism of niacin on modulating S. aureus internalization into bMEC. 

PMID- 24727649
TI  - 'Vape shops' and 'E-Cigarette lounges' open across the USA to promote ENDS.

PMID- 24727648
TI  - Latest progress in tyrosine kinase inhibitors.
AB  - Here we discuss the latest progress in development of some kinase inhibitors such
      as inhibitors of c-MET, LIM and Bcr-Abl kinases. Importantly, many oncogenic
      kinases signal via the mTOR pathway, suggesting a common target for drug
      combinations.

PMID- 24727650
TI  - Rising hospitalization rates for inflammatory bowel disease in Poland.
AB  - INTRODUCTION: The incidence and prevalence of inflammatory bowel disease (IBD) in
      Poland is unknown. OBJECTIVES: We aimed to define the rates of hospitalization
      for IBD and time trends in the past 2 decades. PATIENTS AND METHODS: Data were
      obtained from the database of the National Institute of Public Health (1991-1996
      and 2003-2007). Data on hospitalizations for Crohn's disease (CD) and ulcerative
      colitis (UC) were extracted. Age-, sex-, and disease-specific rates of
      hospitalization per 100,000 population were calculated. RESULTS: During the years
      1991-1996 and 2003-2007, the rate of hospitalization for IBD increased each year,
      rising from 12.50 to 30.61 per 100,000 population. Rising time trends were
      observed in both sexes. The hospitalization rate increased from 3.53 to 9.35 per
      100,000 population for CD and from 8.97 to 21.26 per 100,000 population for UC. A
      rising time trend was observed in hospitalizations for CD in men aged from 0 to
      39 years. A rising time trend for CD in women was observed between the years 2003
      and 2007. The hospitalization rate for UC was higher in men (9.18 to 23.29 per
      100,000) than in women (8.77 to 19.37 per 100,000). Rising time trends for UC
      were observed in the years from 2003 to 2007 in all men and women except for
      those aged from 40 to 64 years. CONCLUSIONS: Hospitalization rates for IBD in
      Poland increased from 1991 to 1996 and from 2003 to 2007, with rising time trends
      in both sexes. For CD, the rising time trend in men was limited to younger age
      groups. The hospitalization rate for UC was significantly higher in men than in
      women.

PMID- 24727651
TI  - Single-molecule analysis of cell surface dynamics in Caenorhabditis elegans
      embryos.
AB  - We describe a general, versatile and minimally invasive method to image single
      molecules near the cell surface that can be applied to any GFP-tagged protein in
      Caenorhabditis elegans embryos. We exploited tunable expression via RNAi and a
      dynamically exchanging monomer pool to achieve fast, continuous single-molecule
      imaging at optimal densities with signal-to-noise ratios adequate for robust
      single-particle tracking (SPT). We introduce a method called smPReSS, single
      molecule photobleaching relaxation to steady state, that infers exchange rates
      from quantitative analysis of single-molecule photobleaching kinetics without
      using SPT. Combining SPT and smPReSS allowed for spatially and temporally
      resolved measurements of protein mobility and exchange kinetics. We used these
      methods to (i) resolve distinct mobility states and spatial variation in exchange
      rates of the polarity protein PAR-6 and (ii) measure spatiotemporal modulation of
      actin filament assembly and disassembly. These methods offer a promising avenue
      to investigate dynamic mechanisms that pattern the embryonic cell surface. 

PMID- 24727652
TI  - Multiscale representation of genomic signals.
AB  - Genomic information is encoded on a wide range of distance scales, ranging from
      tens of bases to megabases. We developed a multiscale framework to analyze and
      visualize the information content of genomic signals. Different types of signals,
      such as G+C content or DNA methylation, are characterized by distinct patterns of
      signal enrichment or depletion across scales spanning several orders of
      magnitude. These patterns are associated with a variety of genomic annotations.
      By integrating the information across all scales, we demonstrated improved
      prediction of gene expression from polymerase II chromatin immunoprecipitation
      sequencing (ChIP-seq) measurements, and we observed that gene expression
      differences in colorectal cancer are related to methylation patterns that extend
      beyond the single-gene scale. Our software is available at
      https://github.com/tknijnen/msr/. 

PMID- 24727653
TI  - Rapid adaptive optical recovery of optimal resolution over large volumes.
AB  - Using a descanned, laser-induced guide star and direct wavefront sensing, we
      demonstrate adaptive correction of complex optical aberrations at high numerical
      aperture (NA) and a 14-ms update rate. This correction permits us to compensate
      for the rapid spatial variation in aberration often encountered in biological
      specimens and to recover diffraction-limited imaging over large volumes (>240 mm
      per side). We applied this to image fine neuronal processes and subcellular
      dynamics within the zebrafish brain. 

PMID- 24727656
TI  - SSVEP recognition using common feature analysis in brain-computer interface.
AB  - BACKGROUND: Canonical correlation analysis (CCA) has been successfully applied to
      steady-state visual evoked potential (SSVEP) recognition for brain-computer
      interface (BCI) application. Although the CCA method outperforms the traditional
      power spectral density analysis through multi-channel detection, it requires
      additionally pre-constructed reference signals of sine-cosine waves. It is likely
      to encounter overfitting in using a short time window since the reference signals
      include no features from training data. NEW METHOD: We consider that a group of
      electroencephalogram (EEG) data trials recorded at a certain stimulus frequency
      on a same subject should share some common features that may bear the real SSVEP
      characteristics. This study therefore proposes a common feature analysis (CFA)
      based method to exploit the latent common features as natural reference signals
      in using correlation analysis for SSVEP recognition. RESULTS: Good performance of
      the CFA method for SSVEP recognition is validated with EEG data recorded from ten
      healthy subjects, in contrast to CCA and a multiway extension of CCA (MCCA).
      COMPARISON WITH EXISTING METHODS: Experimental results indicate that the CFA
      method significantly outperformed the CCA and the MCCA methods for SSVEP
      recognition in using a short time window (i.e., less than 1s). CONCLUSIONS: The
      superiority of the proposed CFA method suggests it is promising for the
      development of a real-time SSVEP-based BCI.

PMID- 24727657
TI  - Introducing the reporting system for thyroid fine-needle aspiration cytology
      according to the new guidelines of the Japan Thyroid Association.
AB  - The Japan Thyroid Association (JTA) recently published new guidelines for
      clinical management of thyroid nodules. This paper introduces their diagnostic
      system for reporting thyroid fine-needle aspiration cytology. There are two
      points where the new reporting system that differs from existing internationally
      accepted ones. The first is the subclassification of the so-called indeterminate
      category, which is divided into 'follicular neoplasm' and 'others'. The second is
      the subclassification of follicular neoplasm into 'favor benign', 'borderline'
      and 'favor malignant'. It is characterized by self-explanatory terminologies as
      to histological type and probability of malignancy to establish further risk
      stratification as well as to facilitate communication between clinicians and
      cytopathologists. The different treatment strategies adopted for thyroid nodules
      is deeply influenced by the particular diagnostic system used for thyroid
      cytology. In Western countries all patients with follicular neoplasms are advised
      to have immediate diagnostic surgery while patients in Japan often undergo
      further risk stratification without immediate surgery. The JTA diagnostic system
      of reporting thyroid cytology is designed for further risk stratification of
      patients with indeterminate cytology. If a surgeon applies diagnostic lobectomy
      to all patients with follicular neoplasm unselectively, this subclassification of
      follicular neoplasm has no practical meaning and is unnecessary. Cytological risk
      stratification of follicular neoplasms is optional and cytopathologists can
      choose either a simple 6-tier system without stratification of follicular
      neoplasm or a complicated 8-tier system depending on their experience in thyroid
      cytology and clinical management. 

PMID- 24727655
TI  - Comparison of leaf proteomes of cassava (Manihot esculenta Crantz) cultivar NZ199
      diploid and autotetraploid genotypes.
AB  - Cassava polyploid breeding has drastically improved our knowledge on increasing
      root yield and its significant tolerance to stresses. In polyploid cassava
      plants, increases in DNA content highly affect cell volumes and anatomical
      structures. However, the mechanism of this effect is poorly understood. The
      purpose of the present study was to compare and validate the changes between
      cassava cultivar NZ199 diploid and autotetraploid at proteomic levels. The
      results showed that leaf proteome of cassava cultivar NZ199 diploid was clearly
      differentiated from its autotetraploid genotype using 2-DE combined MS technique.
      Sixty-five differential protein spots were seen in 2-DE image of autotetraploid
      genotype in comparison with that of diploid. Fifty-two proteins were identified
      by MALDI-TOF-MS/MS, of which 47 were up-regulated and 5 were down-regulated in
      autotetraploid genotype compared with diploid genotype. The classified functions
      of 32 up-regulated proteins were associated with photosynthesis, defense system,
      hydrocyanic acid (HCN) metabolism, protein biosynthesis, chaperones, amino acid
      metabolism and signal transduction. The remarkable variation in photosynthetic
      activity, HCN content and resistance to salt stress between diploid and
      autotetraploid genotypes is closely linked with expression levels of proteomic
      profiles. The analysis of protein interaction networks indicated there are direct
      interactions between the 15 up-regulation proteins involved in the pathways
      described above. This work provides an insight into understanding the protein
      regulation mechanism of cassava polyploid genotype, and gives a clue to improve
      cassava polyploidy breeding in increasing photosynthesis and resistance
      efficiencies. 

PMID- 24727658
TI  - Hydroxyectoine ameliorates preservation injury in deceased after cardiac death
      donors in experimental liver grafts.
AB  - BACKGROUND: Due to the drastic shortage of organ donors, clinicians are
      increasingly considering the use of deceased after cardiac death donors (DCD).
      Compatible solutes like Ectoine and Hydroxyectoine are produced by extremophilic
      bacteria as a cell protectant to survive in harsh environments. We hypothesized
      that the addition of Hydroxyectoine to Histidine-Tryptophan-Ketoglutarate
      solution (HTK) could ameliorate cold ischemic preservation injury of DCD livers.
      MATERIAL AND METHODS: Rat livers were harvested from male Wistar rats weighing
      250-300 g. Three experimental groups (n=5 per group) were studied: (1) CONTROLS:
      cold static storage in HTK for 24 h, (2) DCD: 30-min warm ischemia time and 24-h
      cold static storage in HTK, and (3) DCD+Hydroxyectoine: like DCD, but with 24-h
      cold static storage in HTK+Hydroxyectoine. Viability of the livers was assessed
      after 24 h of preservation by isolated perfusion for 45 min with oxygenated Krebs
      Henseleit buffer solution. RESULTS: (mean +/-SEM, Control vs. DCD vs.
      DCD+Hydroxyectoine) Parenchymal enzyme release was significantly lower in
      DCD+Hydroxyectoine compared to DCD (AST: 9+/-0.54; 56.8+/-2.05; 32.2+/-7.25 U/L,
      ALT: 9.5+/-0.5; 37.75+/-9.6; 17.5+/-4.17 U/L). Bile production at the end of 45
      min reperfusion was significantly higher in DCD+Hydroxyectoine (5.16+/-1.32;
      1.36+/-0.34; 10.75+/-2.24 uL/g liver weight/45 min). Malondialdehyde values were
      significantly lower in DCD+Hydroxyectoine (0.8+/-0.09, 1.14+/-0.18, 0.77+/-0.08
      nmol/mL). Intercellular adhesion molecule-1 showed significantly lower values in
      DCD+Hydroxyectoine (219.07+/-51.79, 431.9+/-35.70, 205.2+/-37.71 pg/mL) and the
      portal venous pressure at 45 min was lower compared to DCD (20.41+/-0.12, 27.47+/
      0.45, 22.08+/-0.78 mmHg). CONCLUSIONS: Our data provide evidence for the
      beneficial role of Hydroxyectoine-modified HTK solution for the preservation of
      DCD livers compared to HTK.

PMID- 24727659
TI  - Identification of novel genomic aberrations in AML-M5 in a level of array CGH.
AB  - To assess the possible existence of unbalanced chromosomal abnormalities and
      delineate the characterization of copy number alterations (CNAs) of acute myeloid
      leukemia-M5 (AML-M5), R-banding karyotype, oligonucelotide array CGH and FISH
      were performed in 24 patients with AML-M5. A total of 117 CNAs with size ranging
      from 0.004 to 146.263 Mb was recognized in 12 of 24 cases, involving all
      chromosomes other than chromosome 1, 4, X and Y. Cryptic CNAs with size less than
      5 Mb accounted for 59.8% of all the CNAs. 12 recurrent chromosomal alterations
      were mapped. Seven out of them were described in the previous AML studies and
      five were new candidate AML-M5 associated CNAs, including gains of 3q26.2-qter
      and 13q31.3 as well as losses of 2q24.2, 8p12 and 14q32. Amplication of 3q26.2
      qter was the sole large recurrent chromosomal anomaly and the pathogenic
      mechanism in AML-M5 was possibly different from the classical recurrent 3q21q26
      abnormality in AML. As a tumor suppressor gene, FOXN3, was singled out from the
      small recurrent CNA of 14q32, however, it is proved that deletion of FOXN3 is a
      common marker of myeloid leukemia rather than a specific marker for AML-M5
      subtype. Moreover, the concurrent amplication of MLL and deletion of CDKN2A were
      noted and it might be associated with AML-M5. The number of CNA did not show a
      significant association with clinico-biological parameters and CR number of the
      22 patients received chemotherapy. This study provided the evidence that array
      CGH served as a complementary platform for routine cytogenetic analysis to
      identify those cryptic alterations in the patients with AML-M5. As a subtype of
      AML, AML-M5 carries both common recurrent CNAs and unique CNAs, which may harbor
      novel oncogenes or tumor suppressor genes. Clarifying the role of these genes
      will contribute to the understanding of leukemogenic network of AML-M5. 

PMID- 24727662
TI  - AACE/ACE disease state commentary: molecular diagnostic testing of thyroid
      nodules with indeterminate cytopathology.
AB  - * Approximately 10 to 25% of fine-needle aspiration (FNA) biopsies yield an
      indeterminate result often labeled as atypia of undetermined significance or
      follicular lesion of undetermined significance (AUS/FLUS) or follicular
      neoplasm/suspicious for follicular neoplasm (FN/SFN). The risk of malignancy
      typically varies between 15 and 30% for these categories. * Although many markers
      are in development and have been studied in a research setting, 2 principal tests
      are currently marketed for use to improve the malignancy risk assessment of
      "indeterminate" thyroid nodules. "Rule In" and "Rule Out" tests attempt to
      confirm or exclude the presence of cancer within a thyroid nodule by means of
      robust positive (PPV) or negative predictive values (NPV), respectively. * The
      Rule In tests determine the presence of single gene point mutations (BRAFV600E or
      RAS) or gene rearrangements (RET/PTC, PAX8/PPARgamma) that have been shown to
      increase the ability to predict cancer, while the Rule Out test (Afirma(r) gene
      expression classifier, GEC) utilizes a proprietary gene expression classifier
      (RNA expression) specifically designed to maximize the ability to define a
      process as benign. * Among the presently available tests, only the BRAFV600E and
      RET/PTC rearrangement are associated with a PPV that approaches 100%. * The
      category of cytologically "indeterminate" nodule (AUS/FLUS, FN/SFN),
      cytopathology practice patterns, and the prevalence of malignancy within the
      population being tested all impact the NPVs and PPVs for the tests in question. *
      At present, molecular testing is meant to complement and not replace clinical
      judgment, sonographic assessment, and visual cytopathology interpretation. * As
      molecular testing is new and advances in the field are regularly occurring,
      clinicians need to stay informed, as recommendations for use within practice are
      expected to evolve.

PMID- 24727660
TI  - Endothelin A receptor antagonism enhances inhibitory effects of anti-ganglioside
      GD2 monoclonal antibody on invasiveness and viability of human osteosarcoma
      cells.
AB  - Endothelin-1 (ET-1)/endothelin A receptor (ETAR) signaling is important for
      osteosarcoma (OS) progression. Monoclonal antibodies (mAbs) targeting ganglioside
      GD2 reportedly inhibit tumor cell viability independent of the immune system. A
      recent study suggests that ganglioside GD2 may play an important role in OS
      progression. In the present study, we for the first time explored the effects of
      anti-GD2 mAb alone or in combination with ETAR antagonist on OS cell invasiveness
      and viability. Human OS cell lines Saos-2, MG-63 and SJSA-1 were treated with
      control IgG (PK136 mAb, 50 ug/mL), anti-GD2 14G2a mAb (50 ug/mL), selective ETAR
      antagonist BQ123 (5 uM), or 14G2a (50 ug/mL)+BQ123 (5 uM). Cells with knockdown
      of ETAR (ETAR-shRNA) with or without 14G2a mAb treatment were also tested. Cells
      treated with selective phosphatidylinositide 3-kinase (PI3K) inhibitor BKM120 (50
      uM) were used as a positive control. Our results showed that BQ123, ETAR-shRNA
      and 14G2a mAb individually decreased cell invasion and viability, matrix
      metalloproteinase-2 (MMP-2) expression and activity, PI3k activity, and
      phosphorylation at serine 473 (ser473) of Akt in OS cells. 14G2a mAb in
      combination with BQ123 or ETAR-shRNA showed significantly stronger inhibitory
      effects compared with each individual treatment. In all three cell lines tested,
      14G2a mAb in combination with BQ123 showed the strongest inhibitory effects. In
      conclusion, we provide the first in vitro evidence that anti-ganglioside GD2
      14G2a mAb effectively inhibits cell invasiveness, MMP-2 expression and activity,
      and cell viability in human OS cells. ETAR antagonist BQ123 significantly
      enhances the inhibitory effects of 14G2a mAb, likely mainly through inhibiting
      the PI3K/Akt pathway. This study adds novel insights into OS treatment, which
      will serve as a solid basis for future in vivo studies on the effects of combined
      treatment of OS with anti-ganglioside GD2 mAbs and ETAR antagonists. 

PMID- 24727664
TI  - Correction.

PMID- 24727663
TI  - TSH threshold for all women undergoing controlled ovarian stimulation.

PMID- 24727665
TI  - Cultures of resistance? A Bourdieusian analysis of doctors' antibiotic
      prescribing.
AB  - The prospect of an 'antimicrobial perfect storm' in the coming decades through
      the emergence and proliferation of multi-resistant organisms has become an urgent
      public health concern. With limited drug discovery solutions foreseeable in the
      immediate future, and with evidence that resistance can be ameliorated by
      optimisation of prescribing, focus currently centres on antibiotic use. In
      hospitals, this is manifest in the development of stewardship programs that aim
      to alter doctors' prescribing behaviour. Yet, in many clinical contexts, doctors'
      antibiotic prescribing continues to elude best practice. In this paper, drawing
      on qualitative interviews with 30 Australian hospital-based doctors in mid-2013,
      we draw on Bourdieu's theory of practice to illustrate that 'sub-optimal'
      antibiotic prescribing is a logical choice within the habitus of the social world
      of the hospital. That is, the rules of the game within the field are heavily
      weighted in favour of the management of immediate clinical risks, reputation and
      concordance with peer practice vis-a-vis longer-term population consequences.
      Antimicrobial resistance is thus a principal of limited significance in the
      hospital. We conclude that understanding the habitus of the hospital and the
      logics underpinning practice is a critical step toward developing governance
      practices that can respond to clinically 'sub-optimal' antibiotic use. 

PMID- 24727666
TI  - Individual and spousal unemployment as predictors of smoking and drinking
      behavior.
AB  - The effects of unemployment on health behaviors, and substance use in particular,
      is still unclear despite substantial existing research. This study aimed to
      assess the effects of individual and spousal unemployment on smoking and alcohol
      consumption. The study was based on eight waves of geocoded Framingham Heart
      Study Offspring Cohort data (US) from 1971 to 2008 that contained social network
      information. We fit three series of models to assess whether lagged 1)
      unemployment, and 2) spousal unemployment predicted odds of being a current
      smoker or drinks consumed per week, adjusting for a range of socioeconomic and
      demographic covariates. Compared with employment, unemployment was associated
      with nearly twice the subsequent odds of smoking, and with increased cigarette
      consumption among male, but not female, smokers. In contrast, unemployment
      predicted a one drink reduction in weekly alcohol consumption, though effects
      varied according to intensity of consumption, and appeared stronger among women.
      While spousal unemployment had no effect on substance use behaviors among men,
      wives responded to husbands' unemployment by reducing their alcohol consumption.
      We conclude that individual, and among women, spousal unemployment predicted
      changes in substance use behaviors, and that the direction of the change was
      substance-dependent. Complex interactions among employment status, sex, and
      intensity and type of consumption appear to be at play and should be investigated
      further. 

PMID- 24727667
TI  - Rapid patterning of 1-D collagenous topography as an ECM protein fibril platform
      for image cytometry.
AB  - Cellular behavior is strongly influenced by the architecture and pattern of its
      interfacing extracellular matrix (ECM). For an artificial culture system which
      could eventually benefit the translation of scientific findings into therapeutic
      development, the system should capture the key characteristics of a physiological
      microenvironment. At the same time, it should also enable standardized, high
      throughput data acquisition. Since an ECM is composed of different fibrous
      proteins, studying cellular interaction with individual fibrils will be of
      physiological relevance. In this study, we employ near-field electrospinning to
      create ordered patterns of collagenous fibrils of gelatin, based on an acetic
      acid and ethyl acetate aqueous co-solvent system. Tunable conformations of micro
      fibrils were directly deposited onto soft polymeric substrates in a single step.
      We observe that global topographical features of straight lines, beads-on
      strings, and curls are dictated by solution conductivity; whereas the finer
      details such as the fiber cross-sectional profile are tuned by solution
      viscosity. Using these fibril constructs as cellular assays, we study EA.hy926
      endothelial cells' response to ROCK inhibition, because of ROCK's key role in the
      regulation of cell shape. The fibril array was shown to modulate the cellular
      morphology towards a pre-capillary cord-like phenotype, which was otherwise not
      observed on a flat 2-D substrate. Further facilitated by quantitative analysis of
      morphological parameters, the fibril platform also provides better dissection in
      the cells' response to a H1152 ROCK inhibitor. In conclusion, the near-field
      electrospun fibril constructs provide a more physiologically-relevant platform
      compared to a featureless 2-D surface, and simultaneously permit statistical
      single-cell image cytometry using conventional microscopy systems. The patterning
      approach described here is also expected to form the basics for depositing other
      protein fibrils, seen among potential applications as culture platforms for drug
      screening. 

PMID- 24727668
TI  - Canonical Wnt signaling regulates the proliferative expansion and differentiation
      of fibrocytes in the murine inner ear.
AB  - Otic fibrocytes tether the cochlear duct to the surrounding otic capsule but are
      also critically involved in maintenance of ion homeostasis in the cochlea, thus,
      perception of sound. The molecular pathways that regulate the development of this
      heterogenous group of cells from mesenchymal precursors are poorly understood.
      Here, we identified epithelial Wnt7a and Wnt7b as possible ligands of Fzd
      mediated beta-catenin (Ctnnb1)-dependent (canonical) Wnt signaling in the
      adjacent undifferentiated periotic mesenchyme (POM). Mice with a conditional
      deletion of Ctnnb1 in the POM exhibited a complete failure of fibrocyte
      differentiation, a severe reduction of mesenchymal cells surrounding the cochlear
      duct, loss of pericochlear spaces, a thickening and partial loss of the bony
      capsule and a secondary disturbance of cochlear duct coiling shortly before
      birth. Analysis at earlier stages revealed that radial patterning of the POM in
      two domains with highly condensed cartilaginous precursors and more loosely
      arranged inner mesenchymal cells occurred normally but that proliferation in the
      inner domain was reduced and cytodifferentiation failed. Cells with
      mis/overexpression of a stabilized form of Ctnnb1 in the entire POM mesenchyme
      sorted to the inner mesenchymal compartment and exhibited increased
      proliferation. Our analysis suggests that Wnt signals from the cochlear duct
      epithelium are crucial to induce differentiation and expansion of fibrocyte
      precursor cells. Our findings emphasize the importance of epithelial-mesenchymal
      signaling in inner ear development.

PMID- 24727669
TI  - Ecdysone differentially regulates metamorphic timing relative to 20
      hydroxyecdysone by antagonizing juvenile hormone in Drosophila melanogaster.
AB  - In insects, a steroid hormone, 20-hydroxyecdysone (20E), plays important roles in
      the regulation of developmental transitions by initiating signaling cascades via
      the ecdysone receptor (EcR). Although 20E has been well characterized as the
      molting hormone, its precursor ecdysone (E) has been considered to be a
      relatively inactive compound because it has little or no effect on classic EcR
      mediated responses. I found that feeding E to wild-type third instar larvae of
      Drosophila melanogaster accelerates the metamorphic timing, which results in
      elevation of lethality during metamorphosis and reduced body size, while 20E has
      only a minor effect. The addition of a juvenile hormone analog (JHA) to E impeded
      their precocious pupariation and thereby rescued the reduced body size. The
      ability of JHA impeding the effect of E was not observed in the Methoprene
      tolerant (Met) and germ-cell expressed (gce) double mutant animals lacking JH
      signaling, indicating that antagonistic action of JH against E is transduced via
      a primary JH receptor, Met, or a product of its homolog, Gce. I also found that
      L3 larvae are susceptible to E around the time when they reach their minimum
      viable weight. These results indicate that E, and not just 20E, is also essential
      for proper regulation of developmental timing and body size. Furthermore, the
      precocious pupariation triggered by E is impeded by the action of JH to ensure
      that animals attain body size to survive metamorphosis.

PMID- 24727670
TI  - Tbx18 is essential for normal development of vasculature network and glomerular
      mesangium in the mammalian kidney.
AB  - Tbx18 has been shown to be essential for ureteral development. However, it
      remains unclear whether it plays a direct role in kidney development. Here we
      addressed this by focusing on examining the pattern and contribution of Tbx18+
      cells in the kidney and its role in kidney vascular development. Expression
      studies and genetic lineage tracing revealed that Tbx18 is expressed in renal
      capsule, vascular smooth muscle cells and pericytes and glomerular mesangial
      cells in the kidney and that Tbx18-expressing progenitors contribute to these
      cell types. Examination of Tbx18(-/-) kidneys revealed large reduction in
      vasculature density and dilation of glomerular capillary loops. While SMA+ cells
      were reduced in the mutant, PDGFRbeta+ cells were seen in early capillary loop
      renal corpuscles in the mutant, but fewer than in the controls, and further
      development of the mesangium failed. Analysis of kidney explants cultured from
      E12.5 excluded the possibility that the defects observed in the mutant were
      caused by ureter obstruction. Reduced proliferation in glomerular tuft and
      increased apoptosis in perivascular mesenchyme were observed in Tbx18(-/-)
      kidneys. Thus, our analyses have identified a novel role of Tbx18 in kidney
      vasculature development.

PMID- 24727671
TI  - Interaction of a partially disordered antisigma factor with its partner, the
      signaling domain of the TonB-dependent transporter HasR.
AB  - Bacteria use diverse signaling pathways to control gene expression in response to
      external stimuli. In Gram-negative bacteria, the binding of a nutrient is sensed
      by an outer membrane transporter. This signal is then transmitted to an antisigma
      factor and subsequently to the cytoplasm where an ECF sigma factor induces
      expression of genes related to the acquisition of this nutrient. The molecular
      interactions involved in this transmembrane signaling are poorly understood and
      structural data on this family of antisigma factor are rare. Here, we present the
      first structural study of the periplasmic domain of an antisigma factor and its
      interaction with the transporter. The study concerns the signaling in the heme
      acquisition system (Has) of Serratia marcescens. Our data support unprecedented
      partially disordered periplasmic domain of an anti-sigma factor HasS in contact
      with a membrane-mimicking environment. We solved the 3D structure of the
      signaling domain of HasR transporter and identified the residues at the HasS-HasR
      interface. Their conservation in several bacteria suggests wider significance of
      the proposed model for the understanding of bacterial transmembrane signaling. 

PMID- 24727672
TI  - Vegetation response and landscape dynamics of Indian Summer Monsoon variations
      during Holocene: an eco-geomorphological appraisal of tropical evergreen forest
      subfossil logs.
AB  - The high rainfall and low sea level during Early Holocene had a significant
      impact on the development and sustenance of dense forest and swamp-marsh cover
      along the southwest coast of India. This heavy rainfall flooded the coastal
      plains, forest flourishing in the abandoned river channels and other low-lying
      areas in midland.The coastline and other areas in lowland of southwestern India
      supply sufficient evidence of tree trunks of wet evergreen forests getting buried
      during the Holocene period under varying thickness of clay, silty-clay and even
      in sand sequences. This preserved subfossil log assemblage forms an excellent
      proxy for eco-geomorphological and palaeoclimate appraisal reported hitherto from
      Indian subcontinent, and complements the available palynological data. The bulk
      of the subfossil logs and partially carbonized wood remains have yielded age
      prior to the Holocene transgression of 6.5 k yrs BP, suggesting therein that
      flooding due to heavy rainfall drowned the forest cover, even extending to parts
      of the present shelf. These preserved logs represent a unique palaeoenvironmental
      database as they contain observable cellular structure. Some of them can even be
      compared to modern analogues. As these woods belong to the Late Pleistocene and
      Holocene, they form a valuable source of climate data that alleviates the lack of
      contemporaneous meteorological records. These palaeoforests along with pollen
      proxies depict the warmer environment in this region, which is consistent with a
      Mid Holocene Thermal Maximum often referred to as Holocene Climate Optimum. Thus,
      the subfossil logs of tropical evergreen forests constitute new indices of Asian
      palaeomonsoon, while their occurrence and preservation are attributed to eco
      geomorphology and hydrological regimes associated with the intensified Asian
      Summer Monsoon, as recorded elsewhere. 

PMID- 24727673
TI  - Risk of myeloid neoplasms after solid organ transplantation.
AB  - Solid organ transplant recipients have elevated cancer risks, owing in part to
      pharmacologic immunosuppression. However, little is known about risks for
      hematologic malignancies of myeloid origin. We linked the US Scientific Registry
      of Transplant Recipients with 15 population-based cancer registries to ascertain
      cancer occurrence among 207 859 solid organ transplants (1987-2009). Solid organ
      transplant recipients had a significantly elevated risk for myeloid neoplasms,
      with standardized incidence ratios (SIRs) of 4.6 (95% confidence interval 3.8
      5.6; N=101) for myelodysplastic syndromes (MDS), 2.7 (2.2-3.2; N=125) for acute
      myeloid leukemia (AML), 2.3 (1.6-3.2; N=36) for chronic myeloid leukemia and 7.2
      (5.4-9.3; N=57) for polycythemia vera. SIRs were highest among younger
      individuals and varied by time since transplantation and organ type (Poisson
      regression P<0.05 for all comparisons). Azathioprine for initial maintenance
      immunosuppression increased risk for MDS (P=0.0002) and AML (2-5 years after
      transplantation, P=0.0163). Overall survival following AML/MDS among transplant
      recipients was inferior to that of similar patients reported to US cancer
      registries (log-rank P<0.0001). Our novel finding of increased risks for specific
      myeloid neoplasms after solid organ transplantation supports a role for immune
      dysfunction in myeloid neoplasm etiology. The increased risks and inferior
      survival should heighten clinician awareness of myeloid neoplasms during follow
      up of transplant recipients. 

PMID- 24727674
TI  - Should persons with acute myeloid leukemia have a transplant in first remission?
AB  - Despite more than 40 years of extensive study, it remains uncertain which
      individuals, if any, with acute myelogenous leukemia (AML) in first remission
      should receive a blood cell or bone marrow transplant versus post-remission
      chemotherapy (or both). Nevertheless, there is a recent trend toward recommending
      more transplants in this setting. We consider four myths underlying this
      recommendation: (1) only individuals achieving second remission benefit from a
      transplant; (2) there is no effective therapy for relapse other than an
      allotransplant; (3) we can accurately predict which individuals with AML in first
      remission need a transplant; and (4) detection of minimal residual disease in
      first remission will resolve this controversy. We discuss these misconceptions
      and suggest approaches to resolve this issue. 

PMID- 24727675
TI  - An aberrant microRNA signature in childhood T-cell lymphoblastic lymphoma
      affecting CDKN1B expression, NOTCH1 and growth factor signaling pathways.

PMID- 24727676
TI  - Notch and NF-kB signaling pathways regulate miR-223/FBXW7 axis in T-cell acute
      lymphoblastic leukemia.
AB  - Notch signaling deregulation is linked to the onset of several tumors including T
      cell acute lymphoblastic leukemia (T-ALL). Deregulated microRNA (miRNA)
      expression is also associated with several cancers, including leukemias. However,
      the transcriptional regulators of miRNAs, as well as the relationships between
      Notch signaling and miRNA deregulation, are poorly understood. To identify miRNAs
      regulated by Notch pathway, we performed microarray-based miRNA profiling of
      several Notch-expressing T-ALL models. Among seven miRNAs, consistently regulated
      by overexpressing or silencing Notch3, we focused our attention on miR-223, whose
      putative promoter analysis revealed a conserved RBPjk binding site, which was
      nested to an NF-kB consensus. Luciferase and chromatin immunoprecipitation assays
      on the promoter region of miR-223 show that both Notch and NF-kB are novel
      coregulatory signals of miR-223 expression, being able to activate cooperatively
      the transcriptional activity of miR-223 promoter. Notably, the Notch-mediated
      activation of miR-223 represses the tumor suppressor FBXW7 in T-ALL cell lines.
      Moreover, we observed the inverse correlation of miR-223 and FBXW7 expression in
      a panel of T-ALL patient-derived xenografts. Finally, we show that miR-223
      inhibition prevents T-ALL resistance to gamma-secretase inhibitor (GSI)
      treatment, suggesting that miR-223 could be involved in GSI sensitivity and its
      inhibition may be exploited in target therapy protocols. 

PMID- 24727678
TI  - Nurse practitioners as primary care providers: creating favorable practice
      environments in New York State and Massachusetts.
AB  - BACKGROUND: Policy makers, health care organizations, and health professionals
      are calling for the expansion of the nurse practitioner (NP) workforce in primary
      care to ensure access to high-quality, cost-effective care. However, to date,
      little is known about NP practice environments in primary care settings and how
      they may affect the expansion of this workforce and their practice. PURPOSES: The
      aims of this study were to investigate NP practice environments in two states,
      Massachusetts (MA) and New York State (NY), and determine the impact of state and
      organization on NP practice environment. METHODOLOGY: A cross-sectional survey
      design was used. Practice environments were measured using the Nurse Practitioner
      Primary Care Organizational Climate Questionnaire in terms of NP-physician
      relations, NP-administration relations, support, NP role comprehension, and NP
      independent practice. In MA, 291 NPs were recruited from the Massachusetts
      Provider Database through mail surveys. In NY, 278 NPs were recruited from the NY
      Nurse Practitioner Association membership list through online surveys. Data were
      collected from May through September 2012. Descriptive statistics were computed.
      Multivariate analysis of variance was conducted to investigate the effect of
      state and organization type on NP practice environments. FINDINGS: Nurse
      practitioners reported favorable relationships with physicians, deficiencies in
      their relationships with administrators, and lack of support. Nurse practitioners
      from MA reported better practice environments. Nurse practitioners from hospital
      affiliated practices perceived poorer practice environments than did NPs
      practicing in physician offices and community health centers. PRACTICE
      IMPLICATIONS: Optimal working relations with physicians and administration,
      access to resources, and clarity in NP role are necessary to create practice
      environments where NPs can function effectively as primary care providers.

PMID- 24727677
TI  - Silencing AML1-ETO gene expression leads to simultaneous activation of both pro
      apoptotic and proliferation signaling.
AB  - The t(8;21)(q22;q22) rearrangement represents the most common chromosomal
      translocation in acute myeloid leukemia (AML). It results in a transcript
      encoding for the fusion protein AML1-ETO (AE) with transcription factor activity.
      AE is considered to be an attractive target for treating t(8;21) leukemia.
      However, AE expression alone is insufficient to cause transformation, and thus
      the potential of such therapy remains unclear. Several genes are deregulated in
      AML cells, including KIT that encodes a tyrosine kinase receptor. Here, we show
      that AML cells transduced with short hairpin RNA vector targeting AE mRNAs have a
      dramatic decrease in growth rate that is caused by induction of apoptosis and
      deregulation of the cell cycle. A reduction in KIT mRNA levels was also observed
      in AE-silenced cells, but silencing KIT expression reduced cell growth but did
      not induce apoptosis. Transcription profiling of cells that escape cell death
      revealed activation of a number of signaling pathways involved in cell survival
      and proliferation. In particular, we find that the extracellular signal-regulated
      kinase 2 (ERK2; also known as mitogen-activated protein kinase 1 (MAPK1)) protein
      could mediate activation of 23 out of 29 (79%) of these upregulated pathways and
      thus may be regarded as the key player in establishing the t(8;21)-positive
      leukemic cells resistant to AE suppression.

PMID- 24727679
TI  - Organizational and environmental correlates of the adoption of a focus strategy
      in U.S. hospices.
AB  - BACKGROUND: The hospice industry has experienced rapid growth in the last decade
      and has become a prominent component of the U.S. health care delivery system. In
      recent decades, the number of hospices serving nursing facility residents has
      increased. However, there is paucity of research on the organizational and
      environmental determinants of this strategic behavior. PURPOSE: The aim of this
      study was to empirically identify the factors associated with the adoption of a
      nursing facility focus strategy in U.S. hospices. A nursing facility focus
      strategy was defined in this study as a strategic choice to target the provision
      of hospice services to skilled nursing facility or nursing home residents.
      METHODOLOGY/APPROACH: This study employed a longitudinal study design with lagged
      independent variables in answering its research questions. Data for the study's
      dependent variables are obtained for the years 2005-2008, whereas data for the
      independent variables are obtained for the years 2004-2007, representing a 1-year
      lag. Mixed effects regression models were used in the multivariate regression
      analyses. FINDINGS: Using a resource dependence framework, the findings from this
      study indicate that organizational size, community wealth, competition, and
      ownership type are important predictors of the adoption of a nursing facility
      focus strategy. PRACTICE IMPLICATIONS: Hospices may be adopting a nursing
      facility focus strategy in response to increasing competition. The decision to
      focus the provision of care to nursing facility residents may be driven by the
      need to secure stability in referrals. Further empirical exploration of the
      performance implications of adopting a nursing facility focus strategy is
      warranted.

PMID- 24727680
TI  - Peptidoglycan inhibits progesterone and androstenedione production in bovine
      ovarian theca cells.
AB  - Uterine bacterial infection perturbs uterine and ovarian functions in postpartum
      dairy cows. Peptidoglycan (PGN) produced by gram-positive bacteria has been shown
      to disrupt the ovarian function in ewes. The aim of this study was to determine
      the effect of PGN on steroid production in bovine theca cells at different stages
      of follicular development. Bovine theca cells isolated from pre- and post
      selection ovarian follicles (<8.5mm and >8.5mm in diameter, respectively) were
      cultured in vitro and challenged with PGN. Steroid production was evaluated by
      measuring progesterone (P4) and androstenedione (A4) concentration in culture
      media after 48 h or 96 h of culture. Bovine theca cells expressed PGN receptors
      including Toll-like receptor 2 and nucleotide-binding oligomerization domain 1
      and 2. Treatment with PGN (1, 10, or 50 MUg/ml) led to a decrease in P4 and A4
      production by theca cells in both pre- and post-selection follicles. The mRNA
      expression of steroidogenic enzymes were decreased by PGN treatment. Moreover, A4
      production was further suppressed when theca cells of post-selection follicles
      were simultaneously treated by PGN and lipopolysaccharide (0.1, 1, or 10 MUg/ml).
      These findings indicate that bacterial toxins may act locally on ovarian
      steroidogenic cells and compromise follicular development in postpartum dairy
      cows.

PMID- 24727681
TI  - Association between ADAM17 promoter polymorphisms and ischemic stroke in a
      Chinese population.
AB  - AIM: Stroke is a leading cause of death and disability worldwide. Most ischemic
      strokes (IS) are caused by atherosclerosis. Recently, the pivotal role of ADAM17
      in atherosclerosis has been thoroughly addressed. However, the association
      between ADAM17 and IS has not yet been thoroughly explored. The present study
      therefore aimed to investigate the association between disintegrin and
      metalloproteinase 17 (ADAM17) gene polymorphisms and the risk of ischemic stroke
      (IS). METHODS: The associations between five ADAM17 promoter polymorphisms and
      the risk of IS were assessed in 342 patients with IS and 296 age-matched healthy
      individuals in a case-control study. RESULTS: The allele and genotype frequencies
      of the ADAM17 polymorphisms (rs11684747, rs11689958, rs12692386, rs55790676 and
      rs1524668) did not differ significantly between the IS patients and healthy
      control group subjects. In addition, no significant associations were detected
      between the ADAM17 haplotypes and IS. The mean intima-media thickness in the IS
      patients was not associated with the ADAM17 polymorphisms. When the IS patients
      were stratified according to their OCSP classification, the genotype frequencies
      of the ADAM17-rs1524668 polymorphism exhibited a significant association with the
      PACI subtype of IS. Moreover, the ADAM17-rs12692386 A>G polymorphism was found to
      be associated with a higher ADAM17 mRNA expression. CONCLUSIONS: The SNPs in the
      ADAM17 promoter region do not appear to be major contributors to the pathogenesis
      of IS. However, the rs12692386 G ADAM17 allele is correlated with a higher
      expression of ADAM17 mRNA, which may play a role in increasing inflammation in IS
      patients. Furthermore, the ADAM17-rs1524668 polymorphism is linked to a higher
      risk of PACI-type stroke, confirming the role of ADAM17 in the pathophysiology of
      PACI, with potentially important therapeutic implications.

PMID- 24727682
TI  - Effects of the consumption of fish meals on the carotid IntimaMedia thickness in
      patients with hypertension: a prospective study.
AB  - AIM: The composition of dietary fat affects various modifiable cardiovascular
      risk factors and cardiovascular outcomes in the general population. We
      investigated the effects of the regular consumption of fish meals on the fatty
      acid composition of red blood cell (RBC) membranes and the relationship of this
      parameter with the carotid intima-media thickness (IMT), an early marker of
      atherosclerosis. METHODS: In 56 hypertensive patients, we measured the carotid
      IMT using ultrasound imaging and the RBC membrane fatty acid composition using
      gas-chromatography and calculated the polyunsaturated to saturated fatty acid
      (PUFA/SFA) ratio. The patients received intensive nutritional counseling and
      three weekly meals of fish containing elevated amounts of PUFA, in order to
      increase the membrane PUFA content. The RBC membrane fatty acid composition and
      IMT were reassessed after one year. RESULTS: At baseline, the membrane PUFA/SFA
      ratio was inversely related to the carotid IMT, and the relationship was
      independent of all major cardiovascular risk factors. At follow-up, the PUFA/SFA
      ratio increased in the RBC membranes of 25 (45%) of 56 patients. The regular
      consumption of fish meals resulted in a decreased carotid IMT only in the
      patients with an increased membrane PUFA/SFA ratio. Changes in the PUFA/SFA ratio
      induced by the dietary intervention were inversely related to the changes in the
      IMT, independent of variations in body mass, blood pressure and plasma lipids.
      CONCLUSIONS: In hypertensive patients, a low RBC membrane PUFA/SFA ratio is
      associated with more prominent vascular damage, and the regular consumption of
      fish reduces the carotid IMT in patients in whom dietary intervention affects the
      membrane fatty acid composition.

PMID- 24727683
TI  - Aryl hydrocarbon receptor mediates indoxyl sulfate-induced cellular senescence in
      human umbilical vein endothelial cells.
AB  - AIM: Vascular senescence, which is accelerated in individuals with chronic kidney
      disease (CKD), contributes to the development of cardio-renal syndrome, and
      various uremic toxins may play important roles in the mechanisms underlying this
      phenomenon. We recently reported that indoxyl sulfate (IS), a uremic toxin,
      directly activates aryl hydrocarbon receptor (AhR) and generates oxidative stress
      through NADPH oxidase-4 in human umbilical vein endothelial cells (HUVECs). In
      the current study, we sought to examine whether IS regulates sirtuin 1 (Sirt1)
      and affects endothelial senescence via AhR activation. METHODS: HUVECs were
      incubated with 500 MUmol/L of IS for the indicated time periods. In order to
      evaluate changes in the senescence of the HUVECs, the number of senescence
      associated beta-galactosidase (SA beta-gal)-positive cells was determined using
      an image analysis software program. The intracellular nicotinamide
      phosphoribosyltransferase (iNampt) activity, cellular NAD(+)/NADPH ratio and
      Sirt1 activity were analyzed according to a colorimetric assay to determine the
      mechanism of cellular senescence. Furthermore, we evaluated the involvement of
      AhR in the senescence-related changes induced by IS using AhR antagonists.
      RESULTS: IS decreased the iNampt activity, NAD(+)/NADPH ratio and Sirt1 activity,
      resulting in an increase in the percentage of SA beta-gal-positive cells. On the
      other hand, the AhR antagonists restored the IS-induced decrease in the NAD(+)
      content in association with an improvement in the iNampt activity and ameliorated
      the senescence-related changes. Taken together, these results indicate that IS
      impairs the iNampt-NAD(+)-Sirt1 system via AhR activation, which in turn promotes
      endothelial senescence. CONCLUSIONS: The IS-AhR pathway induces endothelial
      senescence. Therefore, blocking the effects of AhR in the endothelium may provide
      a new therapeutic tool for treating cardio-renal syndrome.

PMID- 24727684
TI  - Statements.

PMID- 24727685
TI  - Monkey adrenal chromaffin cells express alpha6beta4* nicotinic acetylcholine
      receptors.
AB  - Nicotinic acetylcholine receptors (nAChRs) that contain alpha6 and beta4 subunits
      have been demonstrated functionally in human adrenal chromaffin cells, rat dorsal
      root ganglion neurons, and on noradrenergic terminals in the hippocampus of
      adolescent mice. In human adrenal chromaffin cells, alpha6beta4* nAChRs (the
      asterisk denotes the possible presence of additional subunits) are the
      predominant subtype whereas in rodents, the predominant nAChR is the alpha3beta4*
      subtype. Here we present molecular and pharmacological evidence that chromaffin
      cells from monkey (Macaca mulatta) also express alpha6beta4* receptors. PCR was
      used to show the presence of transcripts for alpha6 and beta4 subunits and
      pharmacological characterization was performed using patch-clamp
      electrophysiology in combination with alpha-conotoxins that target the
      alpha6beta4* subtype. Acetylcholine-evoked currents were sensitive to inhibition
      by BuIA[T5A,P6O] and MII[H9A,L15A]; alpha-conotoxins that inhibit alpha6
      containing nAChRs. Two additional agonists were used to probe for the expression
      of alpha7 and beta2-containing nAChRs. Cells with currents evoked by
      acetylcholine were relatively unresponsive to the alpha7-selctive agonist choline
      but responded to the agonist 5-I-A-85380. These studies provide further insights
      into the properties of natively expressed alpha6beta4* nAChRs. 

PMID- 24727686
TI  - Spin blockade and exchange in Coulomb-confined silicon double quantum dots.
AB  - Electron spins confined to phosphorus donors in silicon are promising candidates
      as qubits because of their long coherence times, exceeding seconds in
      isotopically purified bulk silicon. With the recent demonstrations of
      initialization, readout and coherent manipulation of individual donor electron
      spins, the next challenge towards the realization of a Si:P donor-based quantum
      computer is the demonstration of exchange coupling in two tunnel-coupled
      phosphorus donors. Spin-to-charge conversion via Pauli spin blockade, an
      essential ingredient for reading out individual spin states, is challenging in
      donor-based systems due to the inherently large donor charging energies (~45
      meV), requiring large electric fields (>1 MV m(-1)) to transfer both electron
      spins onto the same donor. Here, in a carefully characterized double donor-dot
      device, we directly observe spin blockade of the first few electrons and measure
      the effective exchange interaction between electron spins in coupled Coulomb
      confined systems.

PMID- 24727687
TI  - Photoinduced doping in heterostructures of graphene and boron nitride.
AB  - The design of stacks of layered materials in which adjacent layers interact by
      van der Waals forces has enabled the combination of various two-dimensional
      crystals with different electrical, optical and mechanical properties as well as
      the emergence of novel physical phenomena and device functionality. Here, we
      report photoinduced doping in van der Waals heterostructures consisting of
      graphene and boron nitride layers. It enables flexible and repeatable writing and
      erasing of charge doping in graphene with visible light. We demonstrate that this
      photoinduced doping maintains the high carrier mobility of the graphene/boron
      nitride heterostructure, thus resembling the modulation doping technique used in
      semiconductor heterojunctions, and can be used to generate spatially varying
      doping profiles such as p-n junctions. We show that this photoinduced doping
      arises from microscopically coupled optical and electrical responses of
      graphene/boron nitride heterostructures, including optical excitation of defect
      transitions in boron nitride, electrical transport in graphene, and charge
      transfer between boron nitride and graphene. 

PMID- 24727688
TI  - Selective uptake of single-walled carbon nanotubes by circulating monocytes for
      enhanced tumour delivery.
AB  - In cancer imaging, nanoparticle biodistribution is typically visualized in living
      subjects using 'bulk' imaging modalities such as magnetic resonance imaging,
      computerized tomography and whole-body fluorescence. Accordingly, nanoparticle
      influx is observed only macroscopically, and the mechanisms by which they target
      cancer remain elusive. Nanoparticles are assumed to accumulate via several
      targeting mechanisms, particularly extravasation (leakage into tumour). Here, we
      show that, in addition to conventional nanoparticle-uptake mechanisms, single
      walled carbon nanotubes are almost exclusively taken up by a single immune cell
      subset, Ly-6C(hi) monocytes (almost 100% uptake in Ly-6C(hi) monocytes, below 3%
      in all other circulating cells), and delivered to the tumour in mice. We also
      demonstrate that a targeting ligand (RGD) conjugated to nanotubes significantly
      enhances the number of single-walled carbon nanotube-loaded monocytes reaching
      the tumour (P < 0.001, day 7 post-injection). The remarkable selectivity of this
      tumour-targeting mechanism demonstrates an advanced immune-based delivery
      strategy for enhancing specific tumour delivery with substantial penetration.

PMID- 24727689
TI  - Observation of the magnetic flux and three-dimensional structure of skyrmion
      lattices by electron holography.
AB  - Skyrmions are nanoscale spin textures that are viewed as promising candidates as
      information carriers in future spintronic devices. Skyrmions have been observed
      using neutron scattering and microscopy techniques. Real-space imaging using
      electrons is a straightforward way to interpret spin configurations by detecting
      the phase shifts due to electromagnetic fields. Here, we report the first
      observation by electron holography of the magnetic flux and the three-dimensional
      spin configuration of a skyrmion lattice in Fe(0.5)Co(0.5)Si thin samples. The
      magnetic flux inside and outside a skyrmion was directly visualized and the
      handedness of the magnetic flux flow was found to be dependent on the direction
      of the applied magnetic field. The electron phase shifts phi in the helical and
      skyrmion phases were determined using samples with a stepped thickness t (from 55
      nm to 510 nm), revealing a linear relationship (phi = 0.00173 t). The phase
      measurements were used to estimate the three-dimensional structures of both the
      helical and skyrmion phases, demonstrating that electron holography is a useful
      tool for studying complex magnetic structures and for three-dimensional, real
      space mapping of magnetic fields.

PMID- 24727690
TI  - Single nucleotide polymorphism (SNP)-strings: an alternative method for assessing
      genetic associations.
AB  - BACKGROUND: Genome-wide association studies (GWAS) identify disease-associations
      for single-nucleotide-polymorphisms (SNPs) from scattered genomic-locations.
      However, SNPs frequently reside on several different SNP-haplotypes, only some of
      which may be disease-associated. This circumstance lowers the observed odds-ratio
      for disease-association. METHODOLOGY/PRINCIPAL FINDINGS: Here we develop a method
      to identify the two SNP-haplotypes, which combine to produce each person's SNP
      genotype over specified chromosomal segments. Two multiple sclerosis (MS)
      associated genetic regions were modeled; DRB1 (a Class II molecule of the major
      histocompatibility complex) and MMEL1 (an endopeptidase that degrades both
      neuropeptides and beta-amyloid). For each locus, we considered sets of eleven
      adjacent SNPs, surrounding the putative disease-associated gene and spanning ~200
      kb of DNA. The SNP-information was converted into an ordered-set of eleven
      numbers (subject-vectors) based on whether a person had zero, one, or two copies
      of particular SNP-variant at each sequential SNP-location. SNP-strings were
      defined as those ordered-combinations of eleven-numbers (0 or 1), representing a
      haplotype, two of which combined to form the observed subject-vector. Subject
      vectors were resolved using probabilistic methods. In both regions, only a small
      number of SNP-strings were present. We compared our method to the SHAPEIT-2
      phasing-algorithm. When the SNP-information spanning 200 kb was used, SHAPEIT-2
      was inaccurate. When the SHAPEIT-2 window was increased to 2,000 kb, the
      concordance between the two methods, in both of these eleven-SNP regions, was
      over 99%, suggesting that, in these regions, both methods were quite accurate.
      Nevertheless, correspondence was not uniformly high over the entire DNA-span but,
      rather, was characterized by alternating peaks and valleys of concordance.
      Moreover, in the valleys of poor-correspondence, SHAPEIT-2 was also inconsistent
      with itself, suggesting that the SNP-string method is more accurate across the
      entire region. CONCLUSIONS/SIGNIFICANCE: Accurate haplotype identification will
      enhance the detection of genetic-associations. The SNP-string method provides a
      simple means to accomplish this and can be extended to cover larger genomic
      regions, thereby improving a GWAS's power, even for those published previously.

PMID- 24727691
TI  - Establishment of quantitative severity evaluation model for spinal cord injury by
      metabolomic fingerprinting.
AB  - Spinal cord injury (SCI) is a devastating event with a limited hope for recovery
      and represents an enormous public health issue. It is crucial to understand the
      disturbances in the metabolic network after SCI to identify injury mechanisms and
      opportunities for treatment intervention. Through plasma 1H-nuclear magnetic
      resonance (NMR) screening, we identified 15 metabolites that made up an "Eigen
      metabolome" capable of distinguishing rats with severe SCI from healthy control
      rats. Forty enzymes regulated these 15 metabolites in the metabolic network. We
      also found that 16 metabolites regulated by 130 enzymes in the metabolic network
      impacted neurobehavioral recovery. Using the Eigen-metabolome, we established a
      linear discrimination model to cluster rats with severe and mild SCI and control
      rats into separate groups and identify the interactive relationships between
      metabolic biomarkers in the global metabolic network. We identified 10 clusters
      in the global metabolic network and defined them as distinct metabolic
      disturbance domains of SCI. Metabolic paths such as retinal, glycerophospholipid,
      arachidonic acid metabolism; NAD-NADPH conversion process, tyrosine metabolism,
      and cadaverine and putrescine metabolism were included. In summary, we presented
      a novel interdisciplinary method that integrates metabolomics and global
      metabolic network analysis to visualize metabolic network disturbances after SCI.
      Our study demonstrated the systems biological study paradigm that integration of
      1H-NMR, metabolomics, and global metabolic network analysis is useful to
      visualize complex metabolic disturbances after severe SCI. Furthermore, our
      findings may provide a new quantitative injury severity evaluation model for
      clinical use. 

PMID- 24727692
TI  - Pretreatment of biomass by torrefaction and carbonization for coal blend used in
      pulverized coal injection.
AB  - To evaluate the utility potential of pretreated biomass in blast furnaces, the
      fuel properties, including fuel ratio, ignition temperature, and burnout, of
      bamboo, oil palm, rice husk, sugarcane bagasse, and Madagascar almond undergoing
      torrefaction and carbonization in a rotary furnace are analyzed and compared to
      those of a high-volatile coal and a low-volatile one used in pulverized coal
      injection (PCI). The energy densities of bamboo and Madagascar almond are
      improved drastically from carbonization, whereas the increase in the calorific
      value of rice husk from the pretreatment is not obvious. Intensifying
      pretreatment extent significantly increases the fuel ratio and ignition
      temperature of biomass, but decreases burnout. The fuel properties of pretreated
      biomass materials are superior to those of the low-volatile coal. For biomass
      torrefied at 300 degrees C or carbonized at temperatures below 500 degrees C, the
      pretreated biomass can be blended with coals for PCI. 

PMID- 24727693
TI  - Impacts of sludge retention time on sludge characteristics and membrane fouling
      in a submerged osmotic membrane bioreactor.
AB  - Sludge retention time (SRT) is a feasible method to alleviate the salt
      accumulation in the osmotic membrane bioreactor (OMBR) by discharging the waste
      activated sludge. In this study, effects of SRT on sludge characteristics and
      membrane fouling were investigated using a submerged OMBR under two SRTs of 10
      and 15d. The results showed that the lower SRT was helpful for alleviating the
      salt accumulation and flux decline. Besides that, the removal of NH3-N was
      significantly influenced by SRT. SRT also had a strong effect on soluble
      microbial products (SMP) and microbial activity due to the variation of salinity.
      Microbial diversity analysis indicated that the high salinity environment in the
      OMBR significantly affected the microbial communities. The flux decline in the
      OMBR was mainly attributed to the reduced driving force resulting from the salt
      accumulation, and the reversible fouling was the dominant forward osmosis (FO)
      membrane fouling in the OMBR. 

PMID- 24727694
TI  - Production of reducing sugar from Enteromorpha intestinalis by hydrothermal and
      enzymatic hydrolysis.
AB  - In this work, to evaluate the efficacy of marine macro-algae Enteromorpha
      intestinalis as a potential bioenergy resource, the effects of reaction
      conditions (solid-to-liquid ratio, reaction temperature, and reaction time) on
      sugars produced by a combined process of hydrothermal and enzymatic hydrolysis
      were investigated. As a result of the hydrothermal hydrolysis, a 7.3g/L (8%
      yield) total reducing sugar was obtained under conditions including solid-to
      liquid ratio of 1:10, reaction temperature of 170 degrees C, and reaction time of
      60min. By subsequent (post-hydrothermal) enzymatic hydrolysis of samples treated
      at 170 degrees C for 30min, a 20.1g/L (22% yield) was achieved. 

PMID- 24727695
TI  - Sequentially alternating pollutant scenarios of phenolic compounds in a
      continuous aerobic granular sludge reactor performing simultaneous partial
      nitritation and o-cresol biodegradation.
AB  - Industrial wastewater treatment plants must operate properly during the transient
      state conditions often found in the industrial production. This study presents
      the performance of simultaneous partial nitritation and o-cresol biodegradation
      in a continuous aerobic granular reactor under sequentially alternating pollutant
      (SAP) scenarios. Three SAP scenarios were imposed during the operation of the
      granular reactor. In each one, a secondary recalcitrant compound (either p
      nitrophenol (PNP), phenol or 2-chlorophenol (2CP)) were added for a short period
      of time to the regular influent containing only ammonium and o-cresol. Partial
      nitritation and o-cresol biodegradation were not inhibited by the presence of PNP
      or phenol and both compounds were fully biodegraded. On the contrary, the
      presence of 2CP strongly inhibited both processes within 2days. However, the
      reactor was recovered in a few days. These findings demonstrate that treatment of
      complex industrial wastewaters with variable influent composition is feasible in
      a continuous aerobic granular reactor. 

PMID- 24727696
TI  - Response of bacterial community structure to seasonal fluctuation and
      anthropogenic pollution on coastal water of Alang-Sosiya ship breaking yard,
      Bhavnagar, India.
AB  - Bacterial community structure was analyzed from coastal water of Alang-Sosiya
      ship breaking yard (ASSBY), world's largest ship breaking yard, near Bhavnagar,
      using 16S rRNA gene sequencing (cultured dependent and culture independent). In
      clone libraries, total 2324 clones were retrieved from seven samples (coastal
      water of ASSBY for three seasons along with one pristine coastal water) which
      were grouped in 525 operational taxonomic units. Proteobacteria was found to be
      dominant in all samples. In pristine samples, Gammaproteobacteria was found to be
      dominant, whereas in polluted samples dominancy of Gammaproteobacteria has
      shifted to Betaproteobacteria and Epsilonproteobacteria. Richness and diversity
      indices also indicated that bacterial community in pristine sample was the most
      diverse followed by summer, monsoon and winter samples. To the best of knowledge,
      this is the first study describing bacterial community structure from coastal
      water of ASSBY, and it suggests that seasonal fluctuation and anthropogenic
      pollutions alters the bacterial community structure. 

PMID- 24727697
TI  - Novel integration strategy for enhancing chalcopyrite bioleaching by
      Acidithiobacillus sp. in a 7-L fermenter.
AB  - An integrated strategy (additional energy substrate-three stage pH control-fed
      batch) was firstly proposed for efficiently improving chalcopyrite bioleaching by
      Acidithiobacillus sp. in a 7-L fermenter. The strain adaptive-growing phase was
      greatly shortened from 8days into 4days with the supplement of additional 2g/L
      Fe(2+)+2g/L S(0). Jarosite passivation was effectively weakened basing on higher
      biomass via the three-stage pH-stat control (pH 1.3-1.0-0.7). The mineral
      substrate inhibition was attenuated by fed-batch fermentation. With the
      integrated strategy, the biochemical reaction was promoted and achieved a better
      balance. Meanwhile, the domination course of A. thiooxidans in the microbial
      community was shortened from 14days to 8days. As the results of integrated
      strategy, the final copper ion and productivity reached 89.1mg/L and 2.23mg/(Ld),
      respectively, which was improved by 52.8% compared to the uncontrolled batch
      bioleaching. The integrated strategy could be further exploited for industrial
      chalcopyrite bioleaching. 

PMID- 24727698
TI  - Inhibitors removal from bio-oil aqueous fraction for increased ethanol
      production.
AB  - Utilization of 1,6-anhydro-beta-d-glucopyranose (levoglucosan) present (11% w/v)
      in the water fraction of bio-oil for ethanol production will facilitate
      improvement in comprehensive utilization of total carbon in biomass. One of the
      major challenges for conversion of anhydrous sugars from the bio-oil water
      fraction to bio-ethanol is the presence of inhibitory compounds that slow or
      impede the microbial fermentation process. Removal of inhibitory compounds was
      first approached by n-butanol extraction. Optimal ratio of n-butanol and bio-oil
      water fraction was 1.8:1. Removal of dissolved n-butanol was completed by
      evaporation. Concentration of sugars in the bio-oil water fraction was performed
      by membrane filtration and freeze drying. Fermentability of the pyrolytic sugars
      was tested by fermentation of hydrolyzed sugars with Saccharomyces pastorianus
      lager yeast. The yield of ethanol produced from pyrolytic sugars in the bio-oil
      water fraction reached a maximum of 98% of the theoretical yield. 

PMID- 24727699
TI  - Techno-economic analysis of wastewater sludge gasification: a decentralized urban
      perspective.
AB  - The successful management of wastewater sludge for small-scale, urban wastewater
      treatment plants, (WWTPs), faces several financial and environmental challenges.
      Common management strategies stabilize sludge for land disposal by microbial
      processes or heat. Such approaches require large footprint processing facilities
      or high energy costs. A new approach considers converting sludge to fuel which
      can be used to produce electricity on-site. This work evaluated several
      thermochemical conversion (TCC) technologies from the perspective of small urban
      WWTPs. Among TCC technologies, air-blown gasification was found to be the most
      suitable approach. A gasification-based generating system was designed and
      simulated in ASPEN Plus(r) to determine net electrical and thermal outputs. A
      technical analysis determined that such a system can be built using currently
      available technologies. Air-blown gasification was found to convert sludge to
      electricity with an efficiency greater than 17%, about triple the efficiency of
      electricity generation using anaerobic digester gas. This level of electricity
      production can offset up to 1/3 of the electrical demands of a typical WWTP.
      Finally, an economic analysis concluded that a gasification-based power system
      can be economically feasible for WWTPs with raw sewage flows above 0.093m(3)/s
      (2.1 million gallons per day), providing a profit of up to $3.5 million over an
      alternative, thermal drying and landfill disposal. 

PMID- 24727700
TI  - Anaerobic digestion of food waste for volatile fatty acids (VFAs) production with
      different types of inoculum: effect of pH.
AB  - Food waste anaerobic fermentation was carried out under acidic conditions using
      inocula based on aerobic activated sludge (Inoculum AE) or anaerobic activated
      sludge (Inoculum AN) for volatile fatty acids (VFAs) production. The results
      showed that food waste hydrolysis increased obviously when Inoculum AN was used
      relative to Inoculum AE at any pH investigated. Hydrolysis at pH 4.0 and
      uncontrolled pH was higher than that at other pHs when either inoculum was used.
      Additionally, VFAs production at pH 6.0 was the highest, regardless of the
      inoculum used. The optimum VFA yields were 0.482g/gVSSremoval with Inoculum AE
      and 0.918g/gVSSremoval with Inoculum AN, which were observed after 4d and 20d of
      fermentation, respectively. VFAs composition analysis showed that butyrate acid
      was the prevalent acid at pH 6.0, followed by acetate acid and propionic acid. 

PMID- 24727701
TI  - NaCl as an effective inducer for lipid accumulation in freshwater microalgae
      Desmodesmus abundans.
AB  - In order to evaluate the efficiency and potential of salt addition-based two
      stage cultivation technology, on the basis of urea as nitrogen source, we
      compared four types of salts (NaCl, NaHCO3, NaS2O3 and NaAc) as inducers for
      lipid production in Desmodesmus abundans. The maximum biomass productivity
      (270.08mgL(-1)d(-1)) was obtained by using 0.25gL(-1) urea. The highest lipid
      productivity (67.08mgL(-1)d(-1)) and better biodiesel quality were realized by
      addition of 20gL(-1) NaCl, and the optimal time point for salt addition was
      determined at 1.79gL(-1) of biomass density. Further cost analysis demonstrated
      this cultivation process was relatively economical. Above results suggest that
      NaCl addition is an economical and applicable strategy for lipid enhancement and
      can be extended for microalgae-based biodiesel production. 

PMID- 24727702
TI  - Two-step sequential liquefaction of lignocellulosic biomass by crude glycerol for
      the production of polyols and polyurethane foams.
AB  - A two-step sequential biomass liquefaction process was developed to produce bio
      based polyols and polyurethane (PU) foams using crude glycerol as a liquefaction
      solvent. The first step, acid-catalyzed liquefaction, was highly effective in
      liquefying biomass, while the second step, base-catalyzed liquefaction, featured
      extensive condensation reactions. By using the developed two-step liquefaction
      process, the polyols produced from lignocellulosic biomass and crude glycerol
      containing 26-40% organic impurities showed hydroxyl numbers ranging from 536 to
      936mgKOH/g, viscosities from 20.6 to 28.0Pas, and molecular weights (Mw) from 444
      to 769g/mol. The PU foams produced had densities ranging from 0.04 to
      0.05g/cm(3), compressive strengths from 223 to 420kPa, and thermal conductivities
      from 32.2 to 38.9mW/mK. Polyols and PU foams produced from the two-step
      liquefaction process had improved properties over their analogs derived from a
      one-step biomass liquefaction by crude glycerol process catalyzed by acid or
      base. 

PMID- 24727703
TI  - Sustained attention to spontaneous thumb sensations activates brain somatosensory
      and other proprioceptive areas.
AB  - The present experiment was designed to test if sustained attention directed to
      the spontaneous sensations of the right or left thumb in the absence of any
      external stimuli is able to activate corresponding somatosensory brain areas.
      After verifying in 34 healthy volunteers that external touch stimuli to either
      thumb effectively activate brain contralateral somatosensory areas, and after
      subtracting attention mechanisms employed in both touch and spontaneous-sensation
      conditions, fMRI evidence was obtained that the primary somatosensory cortex
      (specifically left BA 3a/3b) becomes active when an individual is required to
      attend to the spontaneous sensations of either thumb in the absence of external
      stimuli. In addition, the left superior parietal cortex, anterior cingulate
      gyrus, insula, motor and premotor cortex, left dorsolateral prefrontal cortex,
      Broca's area, and occipital cortices were activated. Moreover, attention to
      spontaneous-sensations revealed an increased connectivity between BA 3a/3b,
      superior frontal gyrus (BA 9) and anterior cingulate cortex (BA 32), probably
      allowing top-down activations of primary somatosensory cortex. We conclude that
      specific primary somatosensory areas in conjunction with other left parieto
      frontal areas are involved in processing proprioceptive and interoceptive bodily
      information that underlies own body-representations and that these networks and
      cognitive functions can be modulated by top-down attentional processes. 

PMID- 24727704
TI  - EuroSCORE II and N-terminal pro-B-type natriuretic peptide for risk evaluation:
      an observational longitudinal study in patients undergoing coronary artery bypass
      graft surgery.
AB  - BACKGROUND: Postoperative heart failure remains the major cause of death after
      cardiac surgery. As N-terminal pro-B-type natriuretic peptide (NT-proBNP) is a
      predictor for postoperative heart failure, the aim was to evaluate if
      preoperative NT-proBNP could provide additional prognostic information to the
      recently launched EuroSCORE II. METHODS: A total of 365 patients with acute
      coronary syndrome (ACS) undergoing isolated coronary artery bypass graft (CABG)
      surgery were studied prospectively. Preoperative NT-proBNP and EuroSCORE II were
      evaluated with regard to severe circulatory failure after operation according to
      prespecified criteria. To assess what clinical outcomes are indicated by NT
      proBNP levels in different risk categories, the patients were stratified
      according to EuroSCORE II. Based on receiver operating characteristics analysis,
      these cohorts were assessed with regard to preoperative NT-proBNP below or above
      1028 ng litre(-1). The follow-up time averaged 4.4 (0.7) yr. RESULTS:
      Preoperative NT-proBNP>=1028 ng litre(-1) [odds ratio (OR) 9.9, 95% confidence
      interval (CI) 1.01-98.9; P=0.049] and EuroSCORE II (OR 1.24, 95% CI 1.06-1.46;
      P=0.008) independently predicted severe circulatory failure after operation. In
      intermediate-risk patients (EuroSCORE II 2.0-10.0), NT-proBNP>=1028 ng litre(-1)
      was associated with a higher incidence of severe circulatory failure (6.6% vs 0%;
      P=0.007), renal failure (14.8% vs 5.4%; P=0.03), stroke (6.6% vs 0.7%; P=0.03),
      longer intensive care unit stay [37 (35) vs 27 (38) h; P=0.002], and worse long
      term survival. CONCLUSIONS: Combining EuroSCORE II and preoperative NT-proBNP
      appears to improve risk prediction with regard to severe circulatory failure
      after isolated CABG for ACS. NT-proBNP may be particularly useful in patients at
      intermediate risk according to EuroSCORE II. CLINICAL TRIAL REGISTRATION:
      NCT00489827.

PMID- 24727705
TI  - Reliability of the American Society of Anesthesiologists physical status scale in
      clinical practice.
AB  - BACKGROUND: Previous studies, which relied on hypothetical cases and chart
      reviews, have questioned the inter-rater reliability of the ASA physical status
      (ASA-PS) scale. We therefore conducted a retrospective cohort study to evaluate
      its inter-rater reliability and validity in clinical practice. METHODS: The
      cohort included all adult patients (>=18 yr) who underwent elective non-cardiac
      surgery at a quaternary-care teaching institution in Toronto, Ontario, Canada,
      from March 2010 to December 2011. We assessed inter-rater reliability by
      comparing ASA-PS scores assigned at the preoperative assessment clinic vs the
      operating theatre. We also assessed the validity of the ASA-PS scale by measuring
      its association with patients' preoperative characteristics and postoperative
      outcomes. RESULTS: The cohort included 10 864 patients, of whom 5.5% were
      classified as ASA I, 42.0% as ASA II, 46.7% as ASA III, and 5.8% as ASA IV. The
      ASA-PS score had moderate inter-rater reliability (kappa 0.61), with 67.0% of
      patients (n=7279) being assigned to the same ASA-PS class in the clinic and
      operating theatre, and 98.6% (n=10 712) of paired assessments being within one
      class of each other. The ASA-PS scale was correlated with patients' age
      (Spearman's rho, 0.23), Charlson comorbidity index (rho=0.24), revised cardiac
      risk index (rho=0.40), and hospital length of stay (rho=0.16). It had moderate
      ability to predict in-hospital mortality (receiver-operating characteristic curve
      area 0.69) and cardiac complications (receiver-operating characteristic curve
      area 0.70). CONCLUSIONS: Consistent with its inherent subjectivity, the ASA-PS
      scale has moderate inter-rater reliability in clinical practice. It also
      demonstrates validity as a marker of patients' preoperative health status.

PMID- 24727707
TI  - Update on enterovirus 71 infection.
AB  - Human enterovirus type 71 (EV71) has emerged as a major cause of viral
      encephalitis in children worldwide. The identified EV71 receptors provide useful
      information for understanding EV71replication and tissue tropism. Host factors
      interact with the internal ribosome entry site (IRES) of EV71 to regulate viral
      translation. However, the specific molecular features of the EV71 genome that
      determine virulence remain unclear. The EV71 capsid protein VP1 region might
      contribute to virulence and neurotropism. Transgenic mice expressing the EV71
      receptor that were infected with the virus exhibited a disease similar to that
      observed in infected humans. Antiviral drug and vaccine development is urgently
      required to prevent EV71 epidemics. Delineating viral host interactions and
      identifying specific mechanisms that might control the neural tropism of EV71
      pathogenesis would be substantial advances. 

PMID- 24727706
TI  - Ascertaining regions affected by GC-biased gene conversion through weak-to-strong
      mutational hotspots.
AB  - A major objective for evolutionary biology is to identify regions affected by
      positive selection. High dN/dS values for proteins and accelerated lineage
      specific substitution rates for non-coding regions are considered classic
      signatures of positive selection. However, these could also be the result of non
      adaptive phenomena, such as GC-biased gene conversion (gBGC), which favors the
      fixation of strong (C/G) over weak (A/T) nucleotides. Recent estimates indicate
      that gBGC affected up to 20% of regions with signatures of positive selection.
      Here we evaluate the impact of gBGC through its molecular signature of weak-to
      strong mutational hotspots. We implemented specific modifications to the test
      proposed by Tang and Lewontin (1999) for identifying regions of differential
      variability and applied it to regions previously investigated for the influence
      of gBGC. While we found significant agreement with previous reports, our results
      suggest a smaller influence of gBGC than previously estimated, warranting further
      development of methods for its detection. 

PMID- 24727708
TI  - The acute effect of smoking a single cigarette on vascular status, SpO2, and
      stress level.
AB  - BACKGROUND: Tobacco use is a major cause of cardiovascular and respiratory
      disease and cancer. It is controversial whether smoking helps relieve stress.
      This study investigated the acute effect of smoking a single cigarette on
      vascular status, SpO2, and stress level. MATERIAL AND METHODS: 38 non-smokers and
      29 smokers were selected as subjects to measure BVOP (Blood Vessel Output Power),
      BVT (Blood Vessel Tension), RBV (Remained Blood Volume), BVAL (Blood Vessel Aging
      Level), SpO2, resistance to stress, and stress score. Pre- and post-experiment
      changes were recorded during a 20-min interval, with smokers being recorded 5 min
      after smoking for the post-experiment. RESULTS: The smoker group showed a
      significant decrease in vascular status (BVOP, RBV, BVAL) compared with the non
      smoker group. SpO2 showed no difference between the smoker group and the non
      smoker group. Smoking showed no effect on stress reduction compared to non
      smoking. CONCLUSIONS: The results of the study indicate that smoking causes a
      negative effect on vascular status and is not beneficial to stress reduction.
      Therefore, quitting smoking is encouraged for better physical and mental health.

PMID- 24727709
TI  - Web-based virtual patients in nursing education: development and validation of
      theory-anchored design and activity models.
AB  - BACKGROUND: Research has shown that nursing students find it difficult to
      translate and apply their theoretical knowledge in a clinical context. Virtual
      patients (VPs) have been proposed as a learning activity that can support nursing
      students in their learning of scientific knowledge and help them integrate theory
      and practice. Although VPs are increasingly used in health care education, they
      still lack a systematic consistency that would allow their reuse outside of their
      original context. There is therefore a need to develop a model for the
      development and implementation of VPs in nursing education. OBJECTIVE: The aim of
      this study was to develop and evaluate a virtual patient model optimized to the
      learning and assessment needs in nursing education. METHODS: The process of
      modeling started by reviewing theoretical frameworks reported in the literature
      and used by practitioners when designing learning and assessment activities. The
      Outcome-Present State Test (OPT) model was chosen as the theoretical framework.
      The model was then, in an iterative manner, developed and optimized to the
      affordances of virtual patients. Content validation was performed with faculty
      both in terms of the relevance of the chosen theories but also its applicability
      in nursing education. The virtual patient nursing model was then instantiated in
      two VPs. The students' perceived usefulness of the VPs was investigated using a
      questionnaire. The result was analyzed using descriptive statistics. RESULTS: A
      virtual patient Nursing Design Model (vpNDM) composed of three layers was
      developed. Layer 1 contains the patient story and ways of interacting with the
      data, Layer 2 includes aspects of the iterative process of clinical reasoning,
      and finally Layer 3 includes measurable outcomes. A virtual patient Nursing
      Activity Model (vpNAM) was also developed as a guide when creating VP-centric
      learning activities. The students perceived the global linear VPs as a relevant
      learning activity for the integration of theory and practice. CONCLUSIONS:
      Virtual patients that are adapted to the nursing paradigm can support nursing
      students' development of clinical reasoning skills. The proposed virtual patient
      nursing design and activity models will allow the systematic development of
      different types of virtual patients from a common model and thereby create
      opportunities for sharing pedagogical designs across technical solutions.

PMID- 24727710
TI  - Migraine is a marker for risk of both ischaemic and haemorrhagic stroke.

PMID- 24727711
TI  - Mailed invitations for colorectal screening are effective in increasing screening
      participation in uninsured adults with faecal immunochemical testing: the
      preferred screening modality.

PMID- 24727712
TI  - First trimester fetal size is inversely and modestly associated with
      cardiovascular risk factors in childhood.

PMID- 24727713
TI  - An intensive outpatient lifestyle modification programme improves measures of
      glycaemia in obese youth.

PMID- 24727714
TI  - Quantitative analysis of RNA-protein interactions on a massively parallel array
      reveals biophysical and evolutionary landscapes.
AB  - RNA-protein interactions drive fundamental biological processes and are targets
      for molecular engineering, yet quantitative and comprehensive understanding of
      the sequence determinants of affinity remains limited. Here we repurpose a high
      throughput sequencing instrument to quantitatively measure binding and
      dissociation of a fluorescently labeled protein to >10(7) RNA targets generated
      on a flow cell surface by in situ transcription and intermolecular tethering of
      RNA to DNA. Studying the MS2 coat protein, we decompose the binding energy
      contributions from primary and secondary RNA structure, and observe that
      differences in affinity are often driven by sequence-specific changes in both
      association and dissociation rates. By analyzing the biophysical constraints and
      modeling mutational paths describing the molecular evolution of MS2 from low- to
      high-affinity hairpins, we quantify widespread molecular epistasis and a long
      hypothesized, structure-dependent preference for G:U base pairs over C:A
      intermediates in evolutionary trajectories. Our results suggest that quantitative
      analysis of RNA on a massively parallel array (RNA-MaP) provides generalizable
      insight into the biophysical basis and evolutionary consequences of sequence
      function relationships. 

PMID- 24727716
TI  - Personality predicts time to remission and clinical status in hypochondriasis
      during a 6-year follow-up.
AB  - We aimed to investigate whether personality characteristics predict time to
      remission and psychiatric status. The follow-up was at most 6 years and was
      performed within the scope of a randomized controlled trial that investigated the
      efficacy of cognitive behavioral therapy, paroxetine, and placebo in
      hypochondriasis. The Life Chart Interview was administered to investigate for
      each year if remission had occurred. Personality was assessed at pretest by the
      Abbreviated Dutch Temperament and Character Inventory. Cox's regression models
      for recurrent events were compared with logistic regression models. Sixteen
      (36.4%) of 44 patients achieved remission during the follow-up period. Cox's
      regression yielded approximately the same results as the logistic regression.
      Being less harm avoidant and more cooperative were associated with a shorter time
      to remission and a remitted state after the follow-up period. Personality
      variables seem to be relevant for describing patients with a more chronic course
      of hypochondriacal complaints. 

PMID- 24727715
TI  - Proteome labeling and protein identification in specific tissues and at specific
      developmental stages in an animal.
AB  - Identifying the proteins synthesized at specific times in cells of interest in an
      animal will facilitate the study of cellular functions and dynamic processes.
      Here we introduce stochastic orthogonal recoding of translation with
      chemoselective modification (SORT-M) to address this challenge. SORT-M involves
      modifying cells to express an orthogonal aminoacyl-tRNA synthetase/tRNA pair to
      enable the incorporation of chemically modifiable analogs of amino acids at
      diverse sense codons in cells in rich media. We apply SORT-M to Drosophila
      melanogaster fed standard food to label and image proteins in specific tissues at
      precise developmental stages with diverse chemistries, including cyclopropene
      tetrazine inverse electron demand Diels-Alder cycloaddition reactions. We also
      use SORT-M to identify proteins synthesized in germ cells of the fly ovary
      without dissection. SORT-M will facilitate the definition of proteins synthesized
      in specific sets of cells to study development, and learning and memory in flies,
      and may be extended to other animals. 

PMID- 24727717
TI  - How does addressing patient's defenses help to repair alliance ruptures in
      psychodynamic psychotherapy?: An exploratory study.
AB  - Interpreting or addressing defenses is an important aspect of psychoanalytic
      technique. Previous research has shown that therapist addressing defenses (TADs)
      can produce a positive effect on alliance. The potential value of TADs during the
      process of alliance rupture and resolution has not yet been documented. We
      selected patients (n = 17) undertaking a short-term dynamic psychotherapy in
      which the therapeutic alliance, measured with the Helping Alliance Questionnaire
      and monitored after each session, showed a pattern of rupture and resolution. Two
      control sessions (5 and 15) were also selected. Presence of TADs was examined in
      each therapist interpretation. Compared with control sessions, rupture sessions
      were characterized by fewer TADs and especially fewer TADs addressing
      specifically intermediate-essentially neurotic-defenses. Resolution sessions were
      characterized by more TADs addressing specifically intermediate defenses. This
      confirms the link between therapist technique and alliance process in
      psychodynamic psychotherapy. 

PMID- 24727718
TI  - Relationship between SWAP-200 patient personality characteristics and patient
      rated alliance early in treatment.
AB  - Research on the therapeutic alliance suggests patient personality characteristics
      to be plausible correlates of alliance formation. To date, research has largely
      focused on the relationship between the alliance and facets of patient
      personality measured via patient self-report, versus personality syndromes.In the
      present study, we assess patient personality using a clinician-rated measure-the
      Shedler-Westen Assessment Procedure-200 (SWAP-200; Shedler and Westen [Assessment
      5:335-355, 1998; Am J Psychiatry 161:1350-1365, 2004; Am J Psychiatry 161:1743
      1754, 2004]; Westen and Shedler [Am J Psychiatry 156:258-272, 1999; Am J
      Psychiatry 156:273-285, 1999])-and investigate the extent to which empirically
      derived personality configurations correlate with patient-rated alliance. The
      study sample consisted of 94 patients receiving psychodynamic psychotherapy at an
      outpatient clinic.The SWAP-200 Dependent Clinical Prototype and Dysphoric:
      Dependent-Masochistic Q-Factors were found to significantly correlate with early
      alliance. Also identified were specific SWAP-200 items that independently
      correlated with early alliance scores.The results of the present study
      demonstrate a relation between patient personality characteristics and
      therapeutic alliance that may serve to further a conceptual understanding of the
      alliance. 

PMID- 24727719
TI  - Does humor influence the stigma of mental illnesses?
AB  - Public stigma is a barrier for people with mental illness. Humor may have the
      potential to decrease stigmatizing attitudes in the context of disclosure.
      Participants completed measures on stigmatizing attitudes and humor style and
      were then randomized to one of three conditions (self-disclosure comedy sketch,
      the same comedy sketch with no disclosure, and a control comedy sketch). After
      reviewing the comedy sketch, the participants repeated the attitude measures and
      provided perceptions of the comic. Humor styles and perceptions significantly
      interacted with condition to reduce stigma. Perceptions of the self-disclosed
      comic were associated with reduced stigma. People exhibiting affiliative humor
      style (i.e., they enjoy making others laugh) were shown to have significantly
      greater stigma changes in the disclosed condition compared with the nondisclosed
      and control conditions. Affiliative humor endorsers also interacted with the
      nondisclosed condition, suggesting that mental health comedy might generally
      reduce stigma in people who use humor to improve relationships. 

PMID- 24727720
TI  - A multivariate twin study of the dimensions of religiosity and common psychiatric
      and substance use disorders.
AB  - The authors sought to decompose the covariance between seven dimensions of
      religiosity and two internalizing psychiatric disorders (major depression and
      phobia) and two externalizing substance use disorders (alcohol dependence and
      nicotine dependence). Significant negative correlations, accounted for by shared
      additive genetic effects, were found between alcohol dependence and six of the
      seven religiosity factors. Additive genetic effects accounted for significant
      negative correlations between nicotine dependence and one religiosity factor,
      social religiosity, and between phobia and unvengefulness. Common environmental
      effects accounted for a significant positive correlation between phobia and the
      factor God as judge. No statistically significant covariance due to genetic or
      environmental effects was found for major depression and any of the seven
      religiosity factors. Overall, although several statistically significant
      bivariate relationships were found, the estimates of covariance due to additive
      genetic effects were modest. 

PMID- 24727721
TI  - Interventions to reduce the consequences of stress in physicians: a review and
      meta-analysis.
AB  - A significant proportion of physicians and medical trainees experience stress
      related anxiety and burnout resulting in increased absenteeism and disability,
      decreased patient satisfaction, and increased rates of medical errors. A review
      and meta-analysis was conducted to examine the effectiveness of interventions
      aimed at addressing stress, anxiety, and burnout in physicians and medical
      trainees. Twelve studies involving 1034 participants were included in three meta
      analyses. Cognitive, behavioral, and mindfulness interventions were associated
      with decreased symptoms of anxiety in physicians (standard differences in means
      [SDM], -1.07; 95% confidence interval [CI], -1.39 to -0.74) and medical students
      (SDM, -0.55; 95% CI, -0.74 to -0.36). Interventions incorporating
      psychoeducation, interpersonal communication, and mindfulness meditation were
      associated with decreased burnout in physicians (SDM, -0.38; 95% CI, -0.49 to 
      0.26). Results from this review and meta-analysis provide support that cognitive,
      behavioral, and mindfulness-based approaches are effective in reducing stress in
      medical students and practicing physicians. There is emerging evidence that these
      models may also contribute to lower levels of burnout in physicians. 

PMID- 24727722
TI  - The essential features of personality disorder in DSM-5: the relationship between
      criteria A and B.
AB  - The essential features of the general criteria for personality disorder in the
      Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), are
      based on impairments in self and interpersonal functioning (criterion A) and
      pathological personality traits (criterion B). The current study investigated the
      relationship between criteria A and B in a German psychiatric sample (N = 149).
      Criterion A was measured by the General Assessment of Personality Disorder
      (GAPD); criterion B, by the Dimensional Assessment of Personality Pathology
      (DAPP) and the Revised NEO Personality Inventory (NEO-PI-R). There was a
      significant relationship between the GAPD, the DAPP, and the NEO-PI-R. The DAPP
      and NEO-PI-R domains increased the predictive validity of the GAPD (by 7.5% and
      14.6%, respectively). The GAPD increased the variance explained by the DAPP by
      1.5% and by the NEO-PI-R by 6.5%. The results suggest a substantial relationship
      between criteria A and B. Criterion B shows incremental validity over criterion A
      but criterion A only in part over criterion B. Future research should investigate
      whether it is possible to assess functional impairment apart from personality
      traits. 

PMID- 24727723
TI  - A study of psychotic symptoms in borderline personality disorder.
AB  - Patients with borderline personality disorder (BPD) report psychotic symptoms,
      but it has been questioned whether they are intrinsic to BPD. Thirty patients
      meeting Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition
      (DSM-IV), criteria for BPD were drawn from a specialist personality disorder
      service. Exclusion criteria included a preexisting clinical diagnosis of
      nonaffective psychotic disorder. Participants underwent structured psychiatric
      interview using the Present State Examination (PSE), lifetime version.
      Approximately 60% of the patients reported psychotic symptoms unrelated to drugs
      or affective disorder. Auditory hallucinations were the most common symptom
      (50%), which were persistent in the majority of cases. A fifth of the patients
      reported delusions, half of whom (three patients) also met DSM-IV criteria for
      schizophrenia, who were previously undiagnosed. The form of auditory
      hallucinations was similar to that in schizophrenia; the content was
      predominantly negative and critical. Persistent auditory hallucinations are
      intrinsic symptoms of BPD. This may inform current diagnostic criteria and have
      implications for approaches to treatment, both pharmacological and psychological.
      The presence of delusions may indicate a comorbid axis I disorder. 

PMID- 24727724
TI  - Longitudinal associations of obesity with affective disorders and suicidality in
      the Baltimore epidemiologic catchment area follow-up study.
AB  - Our aim was to examine the longitudinal associations between obesity and mental
      health variables (psychiatric diagnoses and suicidal behaviors). Data were from
      waves 3 and 4 of the Baltimore Epidemiologic Catchment Area study (N = 1071).
      Participants were aged 30 to 86 years at wave 3 (mean, 47.6 years; SD, 12.8). The
      prevalence of obesity increased from 27.6% to 39.1% during the follow-up.
      Logistic regression analyses revealed no associations between baseline obesity
      and onset of mental disorders or suicidal behaviors between waves 3 and 4 in
      fully adjusted models; however, baseline obesity predicted new-onset suicide
      attempts in models adjusted for sociodemographics and mental disorders. Baseline
      depression predicted weight gain during the 11-year follow-up period (F = 4.014,
      p < 0.05), even after controlling for important confounders. Overall, most mental
      health variables were not associated with obesity, suggesting that clinicians and
      others should be wary of "weight-ism" and avoid making the assumption that higher
      body weight relates to mental health problems. 

PMID- 24727725
TI  - Psychodynamic techniques related to outcome for anxiety disorder patients at
      different points in treatment.
AB  - Although psychodynamic therapy has a well-articulated model of therapeutic change
      for anxiety, few empirical studies have examined specific treatment interventions
      related to symptom improvement. We examined the degree of adherence to a
      psychodynamic model of therapy (Blagys and Hilsenroth [Clin Psychol 7:167-188,
      2000) related to changes in anxiety symptoms across early treatment process.
      Secondary analyses also examined the use of specific psychodynamic techniques
      across early treatment process in relation to symptom change. The current study
      sought to extend the findings of , who found a relationship between the use of
      psychodynamic techniques in the third session (independent clinical ratings) and
      reduction in anxiety symptoms at posttreatment (r = 0.46, p = 0.04). Using the
      same sample of anxiety disorder patients (N = 20), we found a significant
      relationship between psychodynamic technique and posttreatment change in anxiety
      symptoms at the ninth session (r = 0.49, p = 0.03) and the mean levels of
      psychodynamic technique across both third and ninth sessions (r = 0.53, p =
      0.02). In addition, specific psychodynamic techniques demonstrated significant
      relationships or moderate to large effects with posttreatment changes in anxiety
      symptoms at the third and ninth sessions as well as mean ratings across early
      treatment (third and ninth sessions). These findings indicate that therapist
      focus on cyclical intrapersonal patterns in patient actions, feelings, or
      experience as well as suggestions of alternative ways to understand these
      experiences or events not previously recognized by the patient (i.e.,
      interpretation) in the early treatment process were particularly helpful in
      reducing posttreatment anxiety symptoms. Clinical implications and areas for
      future research will be discussed. 

PMID- 24727726
TI  - The reliability of self-assessment of affective state in different phases of
      bipolar disorder.
AB  - Some studies have indicated that the capacity of self-assessment of affective
      state is more compromised during mania than during depression. In the present
      study, we investigated whether the reliability of self-assessment in bipolar
      disorder varies as a function of actual affective state (i.e., euthymia, mania,
      or depression). Sixty-five patients with a diagnosis of type I and type II
      bipolar disorder were evaluated with regard to the occurrence of an affective
      syndrome using the Clinical Global Impressions Scale for use in bipolar illness,
      the Positive and Negative Syndrome Scale, and the Global Assessment of
      Functioning scale. In parallel, we applied the Analog Visual Mood Scale, a self
      assessment tool to evaluate mood changes. The same individual prospectively
      completed the self-assessment scale in different affective states. During
      depression, the patients' evaluation was significantly different from when they
      were in manic or euthymic mood states. However, when in mania, the patients
      evaluated their mood state similarly to when they were euthymic. The bipolar
      patients in mania but not in depression did not reliably evaluate themselves with
      regard to their affective state. 

PMID- 24727727
TI  - Personality traits of patients with multiple sclerosis and their relationship
      with clinical characteristics.
AB  - Few studies have investigated personality characteristics in people with multiple
      sclerosis (MS), and little is known about the relationship between personality
      and clinical characteristics in these patients. We aimed to investigate the
      personality traits of MS patients and their relationship with clinical
      characteristics. The study population consisted of 74 MS patients and age
      matched, sex-matched, and education level-matched healthy controls. All
      participants were instructed to complete the self-administered 240-item
      Temperament and Character Inventory and the Beck Depression Inventory. The MS
      patients exhibited higher harm avoidance (HA) and lower self-directedness scores
      than the control group, although these differences disappeared after controlling
      for depression. Duration of the disease was positively correlated with HA and
      negatively correlated with novelty-seeking scores. Expanded Disability Status
      Scale scores were negatively correlated with reward dependence. Our results
      suggest a possible relationship between personality characteristics and the stage
      of the disease or the degree of damage in MS patients. 

PMID- 24727728
TI  - Interrelated cathepsin S-lowering and LDL subclass profile improvements induced
      by atorvastatin in the plasma of stable angina patients.
AB  - AIM: We hypothesized that, in stable angina patients, atorvastatin therapy lowers
      the cathepsin S (CTSS) concentrations, as assessed non-invasively according to a
      plasma analysis. In addition, the low-density lipoprotein (LDL) and high-density
      lipoprotein (HDL) size and subclasses in the plasma were analysed to establish
      the association between CTSS and lipoprotein metabolism and determine whether
      this association is atorvastatin-sensitive. METHODS: A total of 43 patients with
      stable angina received atorvastatin therapy (20 mg/day, 10 weeks). The plasma
      CTSS mRNA levels, CTSS protein concentrations and CTSS activity, as well as LDL
      and HDL size and subclasses, were analysed before and after treatment. RESULTS:
      Atorvastatin treatment did not change the plasma CTSS mRNA levels, although it
      lowered the plasma CTSS concentrations and activity. An increased plasma CTSS
      concentration and activity were found to be associated with a more atherogenic
      LDL subclass profile (a decreased dominant LDL size and increased percentage of
      small, dense LDL particles). The atorvastatin-induced CTSS-loweringeffect was
      concomitant with an improvement in the LDL subclass profile, and the changes were
      found to be interrelated. Concomitant, interrelated changes in the CTSS levels
      and LDL subclass profiles were found in the LDL phenotype B patients only (a
      dominant LDL diameter of <= 25.5 nm at the start of the study). In this subgroup,
      lowering of the plasma CTSS mRNA level also correlated with lowering of the
      proportion of small, dense LDL particles. CONCLUSIONS: Atorvastatin-induced CTSS
      lowering and LDL subclass profile improvements in the plasma of LDL phenotype B
      patients with stable angina are concomitant and interrelated.

PMID- 24727729
TI  - A low ankle brachial index is associated with an increased risk of cardiovascular
      disease: the Hisayama study.
AB  - AIM: Peripheral artery disease (PAD), defined as a decreased ankle brachial index
      (ABI), is a risk factor for cardiovascular disease; however, few studies have
      assessed the relationship between a low ABI and cardiovascular risks in Asian
      populations. We herein examined the relationship between the ABI and the
      development of cardiovascular disease in a Japanese community. METHODS: A total
      of 2,954community-dwelling Japanese individuals without prior cardiovascular
      disease >= 40years of age were followed up for an average of 7.1years. The
      subjects' ABIs were categorized into the three groups: low (<=0.90), borderline
      (0.91-0.99) and normal (1.00-1.40). We estimated the relationship between the ABI
      and cardiovascular risk using a Cox proportional hazards model. RESULTS: During
      the follow-up period, 134subjects experienced cardiovascular events. The
      incidence of cardiovascular disease across the ABI values was significantly
      different (p<0.001). After adjusting for confounding factors, namely age, sex,
      systolic blood pressure, use of anti-hypertensive drugs, diabetes, total
      cholesterol, high-density lipoprotein cholesterol, obesity, smoking, alcohol
      intake and regular exercise, individuals with a low ABI were at 2.40-fold (95%
      confidence interval [CI] 1.14-5.06) greater risk of cardiovascular disease and
      4.13-fold (95% CI 1.62-10.55) greater risk of coronary heart disease.
      CONCLUSIONS: Our findings suggest that individuals with an ABI of <= 0.90 have an
      increased risk of cardiovascular events, independent from traditional risk
      factors, in the general Japanese population.

PMID- 24727730
TI  - Major soybean maturity gene haplotypes revealed by SNPViz analysis of 72
      sequenced soybean genomes.
AB  - In this Genomics Era, vast amounts of next-generation sequencing data have become
      publicly available for multiple genomes across hundreds of species. Analyses of
      these large-scale datasets can become cumbersome, especially when comparing
      nucleotide polymorphisms across many samples within a dataset and among different
      datasets or organisms. To facilitate the exploration of allelic variation and
      diversity, we have developed and deployed an in-house computer software to
      categorize and visualize these haplotypes. The SNPViz software enables users to
      analyze region-specific haplotypes from single nucleotide polymorphism (SNP)
      datasets for different sequenced genomes. The examination of allelic variation
      and diversity of important soybean [Glycine max (L.) Merr.] flowering time and
      maturity genes may provide additional insight into flowering time regulation and
      enhance researchers' ability to target soybean breeding for particular
      environments. For this study, we utilized two available soybean genomic datasets
      for a total of 72 soybean genotypes encompassing cultivars, landraces, and the
      wild species Glycine soja. The major soybean maturity genes E1, E2, E3, and E4
      along with the Dt1 gene for plant growth architecture were analyzed in an effort
      to determine the number of major haplotypes for each gene, to evaluate the
      consistency of the haplotypes with characterized variant alleles, and to identify
      evidence of artificial selection. The results indicated classification of a small
      number of predominant haplogroups for each gene and important insights into
      possible allelic diversity for each gene within the context of known causative
      mutations. The software has both a stand-alone and web-based version and can be
      used to analyze other genes, examine additional soybean datasets, and view
      similar genome sequence and SNP datasets from other species. 

PMID- 24727731
TI  - Smoking and mental illness in the U.S. population.
AB  - OBJECTIVES: Those with any psychiatric diagnosis have substantially greater rates
      of smoking and are less likely to quit smoking than those with no diagnosis.
      Using nationally representative data, we sought to provide estimates of smoking
      and longitudinal cessation rates by specific psychiatric diagnoses and mental
      health service use. DESIGN AND PARTICIPANTS: Data were analysed from a two-wave
      cohort survey of a U.S. nationally representative sample (non-institutionalised
      adults): the National Epidemiologic Survey on Alcohol and Related Conditions
      (NESARC; 2001-2002, n=43,093; 2004-2005, n=34,653). MAIN OUTCOME MEASURES: We
      examined smoking rates (lifetime, past year and past year heavy) and cross
      sectional quit rates among those with any lifetime or past year psychiatric
      diagnosis (DSM-IV). Importantly, we examined longitudinal quit rates and
      conducted analyses by gender and age categories. RESULTS: Those with any current
      psychiatric diagnosis had 3.23 (95% CI 3.11 to 3.35) times greater odds of
      currently smoking than those with no diagnosis, and were 25% less likely to have
      quit by follow-up (95% CI 20% to 30%). Prevalence varied by specific diagnoses
      (32.4% to 66.7%) as did cessation rates (10.3% to 17.9%). Comorbid disorders were
      associated with higher proportions of heavy smoking. Treatment use was associated
      with greater prevalence of smoking and lower likelihood of cessation.
      CONCLUSIONS: Those with psychiatric diagnoses remained much more likely to smoke
      and less likely to quit, with rates varying by specific diagnosis. Our findings
      highlight the need to improve our ability to address smoking and psychiatric
      comorbidity both within and outside of healthcare settings. Such advancements
      will be vital to reducing mental illness-related disparities in smoking and
      continuing to decrease tobacco use globally.

PMID- 24727732
TI  - Alterations in reward, fear and safety cue discrimination after inactivation of
      the rat prelimbic and infralimbic cortices.
AB  - Accurate discrimination of environmental cues predicting reward, fear, or safety
      is important for survival. The prelimbic and infralimbic cortices are implicated
      in regulating reward-seeking and fear behaviors; however, no studies have
      examined their roles in discriminating among reward, fear, and safety cues. Using
      a discriminative conditioning task that includes presentations of a reward cue
      (paired with a reward pellet), fear cue (paired with footshock), and a compound
      fear+safety cue (no footshock) within the same sessions allowed us to assess the
      flexibility and precision of fear and reward-seeking behaviors to these cues. We
      found that fear behavior was appropriately limited to the fear cue in untreated
      rats, but during infralimbic cortical inactivation, similar levels of fear were
      seen to the fear and compound fear+safety cues. Reward-seeking behavior was also
      appropriately limited to the reward cue in untreated rats. Inactivating the
      prelimbic cortex altered discriminative reward seeking as rats with prelimbic
      inactivation did not increase their reward seeking behavior during the reward cue
      to the same degree as saline controls. Our results imply dissociable roles of the
      two cortical regions: the prelimbic cortex in precise discriminative reward
      seeking and the infralimbic cortex in discriminating between fear and safety
      cues. These data suggest that alterations in the balance of activity between
      areas homologous to the prelimbic and infralimbic cortices may be involved in the
      processes that go awry in anxiety and addiction disorders. 

PMID- 24727733
TI  - Aromatic amino acid activation of signaling pathways in bone marrow mesenchymal
      stem cells depends on oxygen tension.
AB  - The physiologic oxygen pressures inside the bone marrow environment are much
      lower than what is present in the peripheral circulation, ranging from 1-7%,
      compared to values as high as 10-13% in the arteries, lungs and liver. Thus,
      experiments done with bone marrow mesenchymal stem cells (BMMSCs) using standard
      culture conditions may not accurately reflect the true hypoxic bone marrow
      microenvironment. However, since aging is associated with an increased generation
      of reactive oxygen species, experiments done under 21%O2 conditions may actually
      more closely resemble that of the aging bone marrow environment. Aromatic amino
      acids are known to be natural anti-oxidants. We have previously reported that
      aromatic amino acids are potent agonists for stimulating increases in
      intracellular calcium and phospho-c-Raf and in promoting BMMSC differentiation
      down the osteogenic pathway. Our previous experiments were performed under
      normoxic conditions. Thus, we next decided to compare a normoxic (21% O2) vs. a
      hypoxic environment (3% O2) alone or after treatment with aromatic amino acids.
      Reverse-phase protein arrays showed that 3% O2 itself up-regulated proliferative
      pathways. Aromatic amino acids had no additional effect on signaling pathways
      under these conditions. However, under 21%O2 conditions, aromatic amino acids
      could now significantly increase these proliferative pathways over this
      "normoxic" baseline. Pharmacologic studies are consistent with the aromatic amino
      acids activating the extracellular calcium-sensing receptor. The effects of
      aromatic amino acids on BMMSC function in the 21% O2 environment is consistent
      with a potential role for these amino acids in an aging environment as functional
      anti oxidants. 

PMID- 24727734
TI  - Q-FISH measurement of hepatocyte telomere lengths in donor liver and graft after
      pediatric living-donor liver transplantation: donor age affects telomere length
      sustainability.
AB  - Along with the increasing need for living-donor liver transplantation (LDLT), the
      issue of organ shortage has become a serious problem. Therefore, the use of
      organs from elderly donors has been increasing. While the short-term results of
      LDLT have greatly improved, problems affecting the long-term outcome of
      transplant patients remain unsolved. Furthermore, since contradictory data have
      been reported with regard to the relationship between donor age and LT/LDLT
      outcome, the question of whether the use of elderly donors influences the long
      term outcome of a graft after LT/LDLT remains unsettled. To address whether
      hepatocyte telomere length reflects the outcome of LDLT, we analyzed the telomere
      lengths of hepatocytes in informative biopsy samples from 12 paired donors and
      recipients (grafts) of pediatric LDLT more than 5 years after adult-to-child LDLT
      because of primary biliary atresia, using quantitative fluorescence in situ
      hybridization (Q-FISH). The telomere lengths in the paired samples showed a
      robust relationship between the donor and grafted hepatocytes (r = 0.765, p =
      0.0038), demonstrating the feasibility of our Q-FISH method for cell-specific
      evaluation. While 8 pairs showed no significant difference between the telomere
      lengths for the donor and the recipient, the other 4 pairs showed significantly
      shorter telomeres in the recipient than in the donor. Multiple regression
      analysis revealed that the donors in the latter group were older than those in
      the former (p = 0.001). Despite the small number of subjects, this pilot study
      indicates that donor age is a crucial factor affecting telomere length
      sustainability in hepatocytes after pediatric LDLT, and that the telomeres in
      grafted livers may be elongated somewhat longer when the grafts are
      immunologically well controlled. 

PMID- 24727735
TI  - Pesticide use and incident diabetes among wives of farmers in the Agricultural
      Health Study.
AB  - OBJECTIVE: To estimate associations between use of specific agricultural
      pesticides and incident diabetes in women. METHODS: We used data from the
      Agricultural Health Study, a large prospective cohort of pesticide applicators
      and their spouses in Iowa and North Carolina. For comparability with previous
      studies of farmers, we limited analysis to 13 637 farmers' wives who reported
      ever personally mixing or applying pesticides at enrolment (1993-1997), who
      provided complete data on required covariates and diabetes diagnosis and who
      reported no previous diagnosis of diabetes at enrolment. Participants reported
      ever-use of 50 specific pesticides at enrolment and incident diabetes at one of
      two follow-up interviews within an average of 12 years of enrolment. We fit Cox
      proportional hazards models with age as the time scale and adjusting for state
      and body mass index to estimate HRs and 95% CIs for each of the 45 pesticides
      with sufficient users. RESULTS: Five pesticides were positively associated with
      incident diabetes (n=688; 5%): three organophosphates, fonofos (HR=1.56, 95% CI
      1.11 to 2.19), phorate (HR=1.57, 95% CI 1.14 to 2.16) and parathion (HR=1.61, 95%
      CI 1.05 to 2.46); the organochlorine dieldrin (HR=1.99, 95% CI 1.12 to 3.54); and
      the herbicide 2,4,5-T/2,4,5-TP (HR=1.59, 95% CI 1.00 to 2.51). With phorate and
      fonofos together in one model to account for their correlation, risks for both
      remained elevated, though attenuated compared with separate models. CONCLUSIONS:
      Results are consistent with previous studies reporting an association between
      specific organochlorines and diabetes and add to growing evidence that certain
      organophosphates also may increase risk.

PMID- 24727736
TI  - A structural approach to address the healthy-worker survivor effect in
      occupational cohorts: an application in the trucking industry cohort.
AB  - BACKGROUND: Occupational cohort studies are often challenged by the Healthy
      Worker Survivor Effect, which may bias standard methods of analysis. G-estimation
      of structural failure time models is an approach for reducing this type of bias.
      Accelerated failure time models have recently been applied in an occupational
      cohort but cumulative failure time models have not. METHODS: We used g-estimation
      of a cumulative failure time model to assess the effect of working as a long-haul
      driver on ischaemic heart disease mortality in a cohort of 30 448 men employed in
      the unionised US trucking industry in 1985. Exposure was defined by job title and
      based on work records. We also applied g-estimation of an accelerated failure
      time model as a sensitivity analysis and approximated HRs from both models to
      compare them. RESULTS: The risk ratio (RR) obtained from the cumulative failure
      time model, comparing the observed risk under no intervention to the risk had
      nobody ever been exposed as a long-haul driver, was 1.09 (95% CI 1.02 to 1.16).
      The RR comparing the risk had everyone been exposed as long-haul driver for 8
      years to the risk had nobody ever been exposed was 1.20 (95% CI 1.04 to 1.46).
      After HR approximations, accelerated failure time model results were similar.
      CONCLUSIONS: The cumulative failure time model can effectively control time
      varying confounding by Healthy Worker Survivor Effect, and provides an easily
      interpretable effect estimate. RRs estimated from the cumulative failure time
      model indicate an elevated ischaemic heart disease mortality risk for long-haul
      drivers in the US trucking industry.

PMID- 24727737
TI  - Individual-level and plant-level predictors of acute, traumatic occupational
      injuries in a manufacturing cohort.
AB  - OBJECTIVES: Workplace and contextual factors that may affect risk for worker
      injury are not well described. This study used results from an employee job
      satisfaction survey to construct aggregate indicators of the work environment and
      estimate the relative contribution of those factors to injury rates in a
      manufacturing cohort. METHODS: Principal components analysis was used to
      construct four plant-level factors from responses to a 32 question survey of the
      entire workforce, administered in 2006. Multilevel Poisson regression was used to
      evaluate the relationship between injury rate, individual-level and plant-level
      risk factors, unionisation and plant type. RESULTS: Plant-level 'work stress'
      (incident rate ratio (IRR)=0.50, 95% CI 0.28 to 0.90) was significant in the
      multilevel model, indicating the rate of injury for an average individual in that
      plant was halved (conditional on plant) when job stress decreased by a tertile.
      'Overall satisfaction', 'work environment' and 'perception of supervisor' showed
      the same trend but were not significant. Unionisation was protective (IRR=0.40,
      95% CI 0.17 to 0.95) as was any plant type compared with smelter. CONCLUSIONS: We
      demonstrated utility of data from a human resources survey to construct
      indicators of the work environment. Our research suggests that aspects of the
      work environment, particularly work stress and unionisation, may have a
      significant effect on risk for occupational injury, emphasising the need for
      further multilevel studies. Our work would suggest monitoring of employee
      perceptions of job stress and the possible inclusion of stress management as a
      component of risk reduction programmes.

PMID- 24727738
TI  - The IncRNAs PCGEM1 and PRNCR1 are not implicated in castration resistant prostate
      cancer.
AB  - Long noncoding RNAs (IncRNAs) are increasingly implicated in cancer biology,
      contributing to essential cancer cell functions such as proliferation, invasion,
      and metastasis. In prostate cancer, several lncRNAs have been nominated as
      critical actors in disease pathogenesis. Among these, expression of PCGEM1 and
      PRNCR1 has been identified as a possible component in disease progression through
      the coordination of androgen receptor (AR) signaling (Yang et al., Nature 2013,
      see ref. [1]). However, concerns regarding the robustness of these findings have
      been suggested. Here, we sought to evaluate whether PCGEM1 and PRNCR1 are
      associated with prostate cancer. Through a comprehensive analysis of RNA
      sequencing data (RNA-seq), we find evidence that PCGEM1 but not PRNCR1 is
      associated with prostate cancer. We employ a large cohort of >230 high-risk
      prostate cancer patients with long-term outcomes data to show that, in contrast
      to prior reports, neither gene is associated with poor patient outcomes. We
      further observe no evidence that PCGEM1 nor PRNCR1 interact with AR, and neither
      gene is a component of AR signaling. Thus, we conclusively demonstrate that
      PCGEM1 and PRNCR1 are not prognostic lncRNAs in prostate cancer and we refute
      suggestions that these lncRNAs interact in AR signaling. 

PMID- 24727739
TI  - Association of sepsis-related mortality with early increase of TIMP-1/MMP-9
      ratio.
AB  - OBJECTIVE: Higher circulating levels of tissue inhibitor of matrix
      metalloproteinases (TIMP)-1 at the time of severe sepsis diagnosis have been
      reported in nonsurviving than in surviving patients. However, the following
      questions remain unanswered: 1) Does TIMP-1/MMP-9 ratio differ throughout the
      first week of intensive care between surviving and non-surviving patients? 2) Is
      there an association between TIMP-1/MMP-9 ratio and sepsis severity and mortality
      during such period? 3) Could TIMP-1/MMP-9 ratio during the first week be used as
      an early biomarker of sepsis outcome? 4) Is there an association between TIMP
      1/MMP-9 ratio and coagulation state and circulating cytokine levels during the
      first week of intensive care in these patients? The present study sought to
      answer these questions. METHODS: Multicenter, observational and prospective study
      carried out in six Spanish Intensive Care Units (ICUs) of 295 patients with
      severe sepsis. Were measured circulating levels of TIMP-1, MMP-9, tumour necrosis
      factor (TNF)-alpha, interleukin (IL)-10 and plasminogen activator inhibitor (PAI)
      1 at day 1, 4 and 8. End-point was 30-day mortality. RESULTS: We found higher
      TIMP-1/MMP-9 ratio during the first week in non-surviving (n = 98) than in
      surviving patients (n = 197) (p<0.01). Logistic regression analyses showed that
      TIMP-1/MMP-9 ratio at days 1, 4 and 8 was associated with mortality. Receiver
      operating characteristic (ROC) curves showed that TIMP-1/MMP-9 ratio at days 1, 4
      and 8 could predict mortality. There was an association between TIMP-1/MMP-9
      ratio and TNF-alpha, IL-10, PAI-1 and lactic acid levels, SOFA score and platelet
      count at days 1, 4 and 8. CONCLUSIONS: The novel findings of our study were that
      non-surviving septic patients showed persistently higher TIMP-1/MMP-9 ratio than
      survivors ones during the first week, which was associated with severity,
      coagulation state, circulating cytokine levels and mortality; thus representing a
      new biomarker of sepsis outcome.

PMID- 24727740
TI  - Platysma myocutaneous flap interposition in surgical management of large acquired
      post-traumatic tracheoesophageal fistula: A case report.
AB  - INTRODUCTION: Acquired post-traumatic tracheoesophageal fistula (TEF) is an
      uncommon entity requiring early diagnosis. Among the many strategies in surgical
      management, we report a case successfully treated with a single-stage tracheal
      resection and esophageal repair with platysma myocutaneous interposition flap.
      PRESENTATION OF CASE: A 24-year-old man had a motor vehicle accident with head
      injury and cerebral contusion who required mechanical ventilation support. Three
      weeks later, he developed hypersecretion, and recurrent episodes of aspiration
      pneumonia. The chest computed tomography, esophagogastroduodenoscopy, and
      bronchoscopy revealed a large TEF diameter of 3cm at 4.5cm from carina. Single
      stage tracheal resection with primary end-to-end anastomosis and esophageal
      repair with platysma myocutaneous interposition flap was performed. A contrast
      esophagography was done on post-operative day 7 and revealed no leakage. He was
      discharged on post-operative day 10. Esophagogastroduodenoscopy at 1 month
      revealed patient esophageal lumen. At present he is doing well without any
      evidence of complications such as esophageal stricture or fistula. DISCUSSION:
      There are many choices of myocutaneous muscle flaps in trachea and esophageal
      closure or reinforcement. The platysma myocutaneous flap interposition is simple
      with the advantage of reduced bulkiness. Concern on the vascular supply is that
      flap should be elevated with the deep adipofascial tissue under the platysma to
      ensure that the flap survival is not threatened. CONCLUSION: The treatment of
      acquired TEF with platysma myocutaneous flap is an alternative procedure for a
      large uncomplicated TEF as it is effective, technically ease, minimal donor site
      defect and yields good surgical results.

PMID- 24727741
TI  - Coexpression of EpCAM, CD44 variant isoforms and claudin-7 in anaplastic thyroid
      carcinoma.
AB  - BACKGROUND: Anaplastic thyroid cancer is considered to be one of the most
      aggressive human malignancies, and the mean survival time after diagnosis is
      approximately six months, regardless of treatments. This study aimed to examine
      how EpCAM and its related molecules are involved in the characteristics of
      anaplastic thyroid carcinoma. METHODOLOGY/PRINCIPAL FINDINGS: Two differentiated
      thyroid cancer cell lines (TPC-1 and FTC-133), and two anaplastic thyroid cancer
      cell lines (FRO, ACT-1) were analyzed for expression of CD44 standard isoform
      (CD44s), CD44 variant isoforms, and EpCAM, and human aldehyde dehydrogenase-1
      (ALDH1) enzymatic activity using flow cytometry. CD44s expression was higher in
      TPC-1 and FTC-133 than in the FRO and ACT-1, whereas ALDH1 activities were higher
      in FRO and ACT-1 than in TPC-1 and FTC-133. An inverse correlation between CD44s
      expression and ALDH1 activity was observed in all thyroid cancer cell lines. As
      for the expressions of CD44 variant isoforms, ACT-1 showed higher and FRO showed
      moderate CD44v6 expressions, whereas either TPC-1 or FTC-133 showed negative
      CD44v6 expression. EpCAM expressions in FRO and ACT-1 were higher than those in
      TPC-1 and FTC-133, and EpCAM expressions inversely correlated with those of
      CD44s. A positive correlation was observed between EpCAM expression and ALDH1
      activity in thyroid cancer cell lines. In the RT-PCR analysis, the expression
      levels of EpCAM, caludin-7 and ALDH1 in FRO and ATC-1 cells were significantly
      higher than those in TPC-1 and FTC-133 cells. In clinical specimens of thyroid
      cancers, nuclear expression of EpCAM and high expression of CD44v6 were detected
      significantly more frequently in anaplastic carcinomas. CONCLUSIONS/SIGNIFICANCE:
      Our study suggests the possibility that EpCAM, together with CD44v6 and claudin-7
      as well as ALDH1, may be involved in the development of the aggressive phenotype
      of anaplastic thyroid carcinoma. Our findings may suggest a novel therapeutic
      strategy for treatment of anaplastic thyroid carcinoma.

PMID- 24727742
TI  - Would you tell everyone this? Facebook conversations as health promotion
      interventions.
AB  - BACKGROUND: Health promotion interventions on social networking sites can
      communicate individually tailored content to a large audience. User-generated
      content helps to maximize engagement, but health promotion websites have had
      variable success in supporting user engagement. OBJECTIVE: The aim of our study
      was to examine which elements of moderator and participant behavior stimulated
      and maintained interaction with a sexual health promotion site on Facebook.
      METHODS: We examined the pattern and content of posts on a Facebook page. Google
      analytics was used to describe the number of people using the page and viewing
      patterns. A qualitative, thematic approach was used to analyze content. RESULTS:
      During the study period (January 18, 2010, to June 27, 2010), 576 users
      interacted 888 times with the site through 508 posts and 380 comments with 93% of
      content generated by users. The user-generated conversation continued while new
      participants were driven to the site by advertising, but interaction with the
      site ceased rapidly after the advertising stopped. Conversations covered key
      issues on chlamydia and chlamydia testing. Users endorsed testing, celebrated
      their negative results, and modified and questioned key messages. There was
      variation in user approach to the site from sharing of personal experience and
      requesting help to joking about sexually transmitted infection. The moderator
      voice was reactive, unengaged, tolerant, simplistic, and was professional in
      tone. There was no change in the moderator approach throughout the period
      studied. CONCLUSIONS: Our findings suggest this health promotion site provided a
      space for single user posts but not a self-sustaining conversation. Possible
      explanations for this include little new content from the moderator, a definition
      of content too narrow to hold the interest of participants, and limited
      responsiveness to user needs. Implications for health promotion practice include
      the need to consider a life cycle approach to online community development for
      health promotion and the need for a developing moderator strategy to reflect
      this. This strategy should reflect two facets of moderation for online health
      promotion interventions: (1) unengaged and professional oversight to provide a
      safe space for discussion and to maintain information quality, and (2) a more
      engaged and interactive presence designed to maintain interest that generates new
      material for discussion and is responsive to user requests.

PMID- 24727744
TI  - Disruptive patterns of eating behaviors and associated lifestyles in males with
      ADHD.
AB  - BACKGROUND: Attention deficit hyperactivity disorder (ADHD) is a
      neurological/behavioral disorder characterized by inattention or hyperactivity
      and impulsivity, or combined symptomatology. Children with ADHD are predisposed
      to irregular and/or impulsive eating patterns often leading to compromised
      physical condition. The goal of the present study was to statistically evaluate
      parental scoring of patterned eating behaviors and associated lifestyles within a
      cohort of 100 boys diagnosed with ADHD in comparison to age-matched male
      controls. MATERIAL AND METHODS: The study population consisted of 100 boys aged 6
      10 years diagnosed with mixed type ADHD by DSM-IV criteria and 100 aged-matched
      healthy male control subjects. Patterns of eating behaviors and associated
      lifestyles were scored by structured parental interviews using a nominal rating
      scale. RESULTS: Interview scores indicated statistically significant differences
      in patterned eating behaviors in subjects with ADHD in comparison to healthy
      controls. Notably, subjects diagnosed with ADHD exhibited markedly diminished
      adherence to a traditional breakfast, lunch, and dinner schedule, which was
      linked to a significantly higher frequency (>5/day) of irregular eating times. In
      the ADHD cohort, disruptive patterns of eating behaviors were associated with
      diminished nutritional value of ingested food (expressed as lowered content of
      fruits and vegetables) and increased consumption of sweetened beverages.
      CONCLUSIONS: Disruptive patterns of eating behaviors, metabolically unfavorable
      nutritional status, and diminished physical activities of male children diagnosed
      with ADHD are linked to compromised growth and development and appearance of
      metabolic diseases in adulthood.

PMID- 24727743
TI  - Cognitive control in opioid dependence and methadone maintenance treatment.
AB  - BACKGROUND: Substance misuse is associated with cognitive dysfunction. We used a
      stop signal task to examine deficits in cognitive control in individuals with
      opioid dependence (OD). We examined how response inhibition and post-error
      slowing are compromised and whether methadone maintenance treatment (MMT),
      abstinence duration, and psychiatric comorbidity are related to these measures in
      individuals with OD. METHODS: Two-hundred-and-sixty-four men with OD who were
      incarcerated at a detention center and abstinent for up to 2 months (n = 108) or
      at a correctional facility and abstinent for approximately 6 months (n = 156), 65
      OD men under MMT at a psychiatric clinic, and 64 age and education matched
      healthy control (HC) participants were assessed. We computed the stop signal
      reaction time (SSRT) to index the capacity of response inhibition and post-error
      slowing (PES) to represent error-related behavioral adjustment, as in our
      previous work. We examined group effects with analyses of variance and covariance
      analyses, followed by planned comparisons. Specifically, we compared OD and HC
      participants to examine the effects of opioid dependence and MMT and compared OD
      sub-groups to examine the effects of abstinence duration and psychiatric
      comorbidity. RESULTS: The SSRT was significantly prolonged in OD but not MMT
      individuals, as compared to HC. The extent of post-error slowing diminished in OD
      and MMT, as compared to HC (trend; p = 0.061), and there was no difference
      between the OD and MMT groups. Individuals in longer abstinence were no less
      impaired in these measures. Furthermore, these results remained when psychiatric
      comorbidities including misuse of other substances were accounted for.
      CONCLUSIONS: Methadone treatment appears to be associated with relatively intact
      cognitive control in opioid dependent individuals. MMT may facilitate public
      health by augmenting cognitive control and thereby mitigating risky behaviors in
      heroin addicts.

PMID- 24727745
TI  - Species-independent down-regulation of leaf photosynthesis and respiration in
      response to shading: evidence from six temperate tree species.
AB  - The ability to down-regulate leaf maximum net photosynthetic capacity (Amax) and
      dark respiration rate (Rdark) in response to shading is thought to be an
      important adaptation of trees to the wide range of light environments that they
      are exposed to across space and time. A simple, general rule that accurately
      described this down-regulation would improve carbon cycle models and enhance our
      understanding of how forest successional diversity is maintained. In this paper,
      we investigated the light response of Amax and Rdark for saplings of six
      temperate forest tree species in New Jersey, USA, and formulated a simple model
      of down-regulation that could be incorporated into carbon cycle models. We found
      that full-sun values of Amax and Rdark differed significantly among species, but
      the rate of down-regulation (proportional decrease in Amax or Rdark relative to
      the full-sun value) in response to shade was not significantly species- or taxon
      specific. Shade leaves of sun-grown plants appear to follow the same pattern of
      down-regulation in response to shade as leaves of shade-grown plants. Given the
      light level above a leaf and one species-specific number (either the full-sun
      Amax or full-sun Rdark), we provide a formula that can accurately predict the
      leaf's Amax and Rdark. We further show that most of the down regulation of per
      unit area Rdark and Amax is caused by reductions in leaf mass per unit area
      (LMA): as light decreases, leaves get thinner, while per unit mass Amax and Rdark
      remain approximately constant. 

PMID- 24727746
TI  - Critical importance of long-term adherence to care in HIV infected patients in
      the cART era: new insights from Pneumocystis jirovecii pneumonia cases over 2004
      2011 in the FHDH-ANRS CO4 cohort.
AB  - OBJECTIVE: To describe characteristics and outcomes of HIV-infected patients with
      Pneumocystis jirovecii pneumonia (PCP) over 2004-2011 in France, in particular in
      those previously enrolled (PE) in the French Hospital Database on HIV (FHDH).
      METHODS: PE patients with an incident PCP were compared with patients with an
      inaugural PCP revealing HIV infection (reference). Adequate adherence to care was
      defined as a CD4 measurement at least every 6 months. Immune reconstitution
      (CD4>=200/mm3) and risk of death were studied using Kaplan-Meier estimates and
      multivariable Cox proportional hazards models. RESULTS: In a context of a
      decreasing incidence of PCP, 1259 HIV-infected patients had a PCP diagnosis, and
      593 (47%) were PE patients of whom 161 (27%) have had a prior history of AIDS
      defining clinical illness (prior ADI). Median time since enrolment was 8 years
      for PE patients; 74% had received cART. Median proportion of time with adequate
      adherence to care was 85% (IQR, 66-96) for all FHDH enrollees, but only 45% (IQR,
      1-81) for PE patients during the 2 years before PCP. Median CD4 cell count
      (38/mm3) and HIV viral load (5.2 log10 copies/ml) at PCP diagnosis did not differ
      between PE patients and the reference group. Three year mortality rate of 25% was
      observed for PE prior ADI group, higher than in PE non-prior ADI group (8%) and
      the reference group (9%) (p<0.0001). In the PE prior ADI group, poor prognosis
      remained even after adjustment for virological control and immune reconstitution
      (HR, 2.4 [95%CI, 1.5-3.7]). CONCLUSION: Almost 50% of PCP diagnoses in HIV
      infected patients occurred presently in patients already in care, mainly with a
      previous cART prescription but with waning adherence to care. Having repeated ADI
      is contributing to the risk of death beyond its impact on immune reconstitution
      and viral suppression: special efforts must be undertaken to maintain those
      patients in care.

PMID- 24727748
TI  - Inhibition effect of secondary metabolites accumulated in a pervaporation
      membrane bioreactor on ethanol fermentation of Saccharomyces cerevisiae.
AB  - The secondary metabolites accumulated in a pervaporation membrane bioreactor
      during ethanol fermentation were mostly composed of acetic acid, lactic acid,
      propionic acid, citric acid, succinic acid and glycerol. The inhibition effect of
      these compounds at a broad concentration range was studied through ethanol
      fermentation by Saccharomyces cerevisiae. An increasing concentration of the
      secondary metabolites led to longer lag time and a reduction of cell growth. The
      specific cell growth rate, cell yield, ethanol productivity were only 0.061 h(
      1), 0.024, 0.47 g L(-1) h(-1) respectively, when the medium contained 3.12 g of
      acetic acid, 10.23 g of lactic acid, 2.72 g of propionic acid, 1.35 g of citric
      acid, 2.26 g of succinic acid and 49.25 g of glycerol per liter (a concentration
      level in pervaporation membrane bioreactor at later fermentation period). By
      increasing pH of the medium to 6.0-8.0, the inhibition of these secondary
      metabolites could be greatly relieved.

PMID- 24727749
TI  - PTSD perpetuates pain in children with traumatic brain injury.
AB  - OBJECTIVE: This study tested theoretical models of the relationship between pain
      and posttraumatic stress disorder (PTSD) in children with traumatic brain injury
      (TBI). METHODS: Participants consisted of 195 children aged 6-15 years presenting
      to 1 of 3 Australian hospitals following a mild-severe TBI. Children were
      assessed at 3, 6, and 18 months after their accident for PTSD (via the Clinician
      Administered PTSD Scale for Children and Adolescents [CAPS-CA] clinical
      interview) as well as physical pain (via the Child Health Questionnaire, 50-item
      version [CHQ-PF50]). Trained clinicians administered the CAPS-CA at home visits,
      and the CHQ-PF50 was collected through questionnaires. RESULTS: Structural
      equation modeling found the data supported the mutual maintenance model and also
      the nested perpetual avoidance model. CONCLUSIONS: Both models indicate PTSD is
      driving the presence of pain, and not vice versa. A fourth model stating this was
      proposed. Therefore, it may be useful to address PTSD symptoms in treating child
      pain for expediting recovery.

PMID- 24727750
TI  - Achievement of developmental milestones in emerging and young adults with and
      without pediatric chronic illness--a meta-analysis.
AB  - OBJECTIVE: The objective of the meta-analysis is to integrate results on the
      achievement of developmental milestones in emerging and young adults with chronic
      pediatric physical illness. METHODS: Through electronic databases and cross
      referencing, 165 comparative studies were identified. Random-effects meta
      analysis was computed. RESULTS: Emerging and young adults with chronic pediatric
      illness had lower rates of finishing advanced education, finding employment,
      leaving the parental home, marrying, and becoming parents than healthy peers;
      between-group differences ranged from 22 to 38%. They also had lower income
      levels than healthy peers. Stronger differences were found for respondents with
      neurological illnesses and sensory impairment than in individuals with other
      chronic diseases. Lower success rates were also observed if the
      illness/disability is highly visible to others and in the case of longer illness
      duration. CONCLUSIONS: Interventions are recommended aimed at preventing and
      reducing lower rates of mastering the adult milestones of individuals with
      pediatric chronic illness.

PMID- 24727751
TI  - Temporal-spatial neural activation patterns linked to perceptual encoding of
      emotional salience.
AB  - It is well known that we continuously filter incoming sensory information,
      selectively allocating attention to what is important while suppressing
      distracting or irrelevant information. Yet questions remain about spatiotemporal
      patterns of neural processes underlying attentional biases toward emotionally
      significant aspects of the world. One index of affectively biased attention is an
      emotional variant of an attentional blink (AB) paradigm, which reveals enhanced
      perceptual encoding for emotionally salient over neutral stimuli under conditions
      of limited executive attention. The present study took advantage of the high
      spatial and temporal resolution of magnetoencephalography (MEG) to investigate
      neural activation related to emotional and neutral targets in an AB task. MEG
      data were collected while participants performed a rapid stimulus visual
      presentation task in which two target stimuli were embedded in a stream of
      distractor words. The first target (T1) was a number and the second (T2) either
      an emotionally salient or neutral word. Behavioural results replicated previous
      findings of greater accuracy for emotionally salient than neutral T2 words. MEG
      source analyses showed that activation in orbitofrontal cortex, characterized by
      greater power in the theta and alpha bands, and dorsolateral prefrontal
      activation were associated with successful perceptual encoding of emotionally
      salient relative to neutral words. These effects were observed between 250 and
      550 ms, latencies associated with discrimination of perceived from unperceived
      stimuli. These data suggest that important nodes of both emotional salience and
      frontoparietal executive systems are associated with the emotional modulation of
      the attentional blink. 

PMID- 24727754
TI  - Is this really the RNAissance?

PMID- 24727752
TI  - Association between serum levels of carotenoids and serum asymmetric
      dimethylarginine levels in Japanese subjects.
AB  - BACKGROUND: Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of
      endothelium nitric oxide synthase (NOS). ADMA binds to a substrate-binding site
      of NOS and then inhibits nitric oxide production from vascular endothelial cells.
      Elevated ADMA levels are a risk factor for cardiovascular disease. Recently, it
      was reported that plasma ADMA levels were negatively correlated with vegetable
      and fruit consumption. The purpose of this study was to examine the association
      between serum levels of carotenoids and serum ADMA levels in Japanese subjects.
      METHODS: We conducted a cross-sectional study of 470 subjects (203 men and 267
      women) who attended a health examination in August 2011. Serum levels of several
      carotenoids were separately measured by high-performance liquid chromatography.
      Serum ADMA levels were determined by using an enzyme-linked immunosorbent assay
      kit. RESULTS: In women, the multivariate-adjusted odds ratios (ORs) of elevated
      serum ADMA levels were significantly decreased in the highest tertile for beta
      cryptoxanthin (OR 0.47, 95% CI 0.23-0.95), alpha-carotene (OR 0.39, 95% CI 0.18
      0.79), and beta-carotene (OR 0.36, 95% CI 0.17-0.73) compared to the lowest
      tertile. In men, significantly decreased ORs were observed in the highest
      tertiles of serum zeaxanthin/lutein (OR 0.23, 95% CI 0.06-0.69) and alpha
      carotene (OR 0.26, 95% CI 0.07-0.82), and in the middle and the highest tertiles
      of serum beta-carotene (OR 0.27, 95% CI 0.09-0.74 and OR 0.20, 95% CI 0.03-0.88,
      respectively) when the tertile cutoff points of women were extrapolated to men.
      CONCLUSIONS: Higher serum levels of carotenoids, such as alpha-carotene and beta
      carotene, may help to prevent elevated serum ADMA levels in Japanese subjects.

PMID- 24727755
TI  - Markets, venture investors and big pharma interest in RNAi soars.

PMID- 24727753
TI  - Self-reported snoring and carotid atherosclerosis in middle-aged and older
      adults: the Korean Multi-Rural Communities Cohort Study.
AB  - BACKGROUND: We investigated the relation of self-reported snoring with carotid
      intima-media thickness (IMT) and plaque in community-dwelling middle-aged and
      older adults. METHODS: In total, 7330 community-dwelling subjects in the Korean
      Multi-Rural Communities Cohort Study were included in the analysis. Common
      carotid artery IMT (CCA-IMT) and plaque were evaluated by high-resolution B-mode
      ultrasonography. Snoring status was evaluated using a structured interview.
      RESULTS: Snorers had a significantly greater average CCA-IMT than non-snorers
      (0.726 vs 0.713 mm; P < 0.001), after adjusting for age and gender. The odds
      ratios (OR) for high CCA-IMT (fifth quintile) were significantly higher for
      snorers than for non-snorers in multivariate-adjusted analysis (OR 1.25, 95%
      confidence interval [CI] 1.10-1.42). However, there was no significant
      relationship between snoring and carotid plaques. CONCLUSIONS: Our data suggest
      that self-reported snoring is significantly associated with increased IMT, but
      not with the presence of plaques. These findings suggest that early screening and
      intervention for snoring in the general population are needed to prevent adverse
      cardiovascular events.

PMID- 24727756
TI  - First integrin inhibitor since Tysabri nears approval for IBD.

PMID- 24727759
TI  - Amgen and Regeneron push for a genetic renaissance in drug discovery.

PMID- 24727761
TI  - First recombinant Factor XIII approved.

PMID- 24727763
TI  - Myriad diversifies, fights rearguard action on patents.

PMID- 24727766
TI  - Roche bets on alpha-synuclein for Parkinson's.

PMID- 24727767
TI  - Acquiring orphans.

PMID- 24727768
TI  - Startups on the menu: Circuit Therapeutics.

PMID- 24727769
TI  - Interactive visualization and analysis of large-scale sequencing datasets using
      ZENBU.

PMID- 24727770
TI  - OpenSWATH enables automated, targeted analysis of data-independent acquisition MS
      data.

PMID- 24727772
TI  - From the analyst's couch: The outlook for biotech exits.

PMID- 24727771
TI  - ProteomeXchange provides globally coordinated proteomics data submission and
      dissemination.

PMID- 24727773
TI  - Nature Biotechnology's academic spinouts of 2013.

PMID- 24727775
TI  - Casting light on pain.

PMID- 24727776
TI  - E. coli network upgrade.

PMID- 24727777
TI  - You are what you eat.

PMID- 24727783
TI  - Profiling the reform-era life sciences executive.

PMID- 24727785
TI  - Incivility in the hospital environment: the nurse educator-staff nurse
      relationship.
AB  - Occurrences of incivility in nurse educator-staff nurse relationship studies are
      limited. A qualitative methodology (n = 6) was used to investigate nurse
      educators' perceptions of the main stressors for nurses during educational
      experiences. Identification of uncivil traits as seen by nurse educators and
      perceived role of nursing leaders in addressing incivility in the workplace were
      also identified.

PMID- 24727787
TI  - Invasive leader cells: metastatic oncotarget.

PMID- 24727786
TI  - Evolution of the F-box gene family in Euarchontoglires: gene number variation and
      selection patterns.
AB  - F-box proteins are substrate adaptors used by the SKP1-CUL1-F-box protein (SCF)
      complex, a type of E3 ubiquitin ligase complex in the ubiquitin proteasome system
      (UPS). SCF-mediated ubiquitylation regulates proteolysis of hundreds of cellular
      proteins involved in key signaling and disease systems. However, our knowledge of
      the evolution of the F-box gene family in Euarchontoglires is limited. In the
      present study, 559 F-box genes and nine related pseudogenes were identified in
      eight genomes. Lineage-specific gene gain and loss events occurred during the
      evolution of Euarchontoglires, resulting in varying F-box gene numbers ranging
      from 66 to 81 among the eight species. Both tandem duplication and
      retrotransposition were found to have contributed to the increase of F-box gene
      number, whereas mutation in the F-box domain was the main mechanism responsible
      for reduction in the number of F-box genes, resulting in a balance of expansion
      and contraction in the F-box gene family. Thus, the Euarchontoglire F-box gene
      family evolved under a birth-and-death model. Signatures of positive selection
      were detected in substrate-recognizing domains of multiple F-box proteins, and
      adaptive changes played a role in evolution of the Euarchontoglire F-box gene
      family. In addition, single nucleotide polymorphism (SNP) distributions were
      found to be highly non-random among different regions of F-box genes in 1092
      human individuals, with domain regions having a significantly lower number of non
      synonymous SNPs. 

PMID- 24727788
TI  - The nodule conductance to O2 diffusion increases with phytase activity in N2
      fixing Phaseolus vulgaris L.
AB  - To understand the relationship between phosphorus use efficiency (PUE) and
      respiration for symbiotic nitrogen fixation (SNF) in legume nodules, six
      recombinant inbred lines of common bean (RIL Phaseolus vulgaris L.), contrasting
      in PUE for SNF, were inoculated with Rhizobium tropici CIAT899, and grown under
      hydroaeroponic culture with sufficient versus deficient P supply (250 versus 75
      MUmol P plant(-1) week(-1)). At the flowering stage, the biomass of plants and
      phytase activity in nodules were analyzed after measuring O2 uptake by nodulated
      roots. Our results show that the P-deficiency significantly increased the phytase
      activity in nodules of all RILs though with highest extent for RILs 147, 29 and
      83 (ca 45%). This increase in phytase activity was associated with an increase in
      nodule respiration (ca 22%) and in use of the rhizobial symbiosis (ca 21%). A
      significant correlation was found under P-deficiency between nodule O2
      permeability and phytase activity in nodules for RILs 104, 34 and 115. This
      observation is to our knowledge the first description of a correlation between O2
      permeability and phytase activity of a legume nodule. It is concluded that the
      variation of phytase activity in nodules can increase the internal utilization of
      P and might be involved in the regulation of nodule permeability for the
      respiration linked with SNF and the adaptation to P-deficiency.

PMID- 24727789
TI  - Expression of flavonoid biosynthesis genes and accumulation of flavonoid in wheat
      leaves in response to drought stress.
AB  - Flavonoids are the low molecular weight polyphenolic secondary metabolic
      compounds, and have various functions in growth, development, reproduction, and
      stress defense. However, little is known about the roles of the key enzymes in
      the flavonoids biosynthesis pathway in response to drought stress in winter
      wheat. Here, we investigated the expression pattern of flavonoids biosynthesis
      genes and accumulation of flavonoids in wheat leaves under drought stress.
      Quantitative real-time PCR analysis showed that there were a rapid increase in
      expression levels of TaCHS, TaCHI, TaF3H, TaFNS, TaFLS, TaDFR, and TaANS under
      drought stress in two wheat cultivars Aikang 58 (AK) and Chinese Spring (CS). The
      cultivar CS exhibited higher genes expression levels of TaCHS, TaCHI, TaF3H,
      TaFLS, TaDFR, and TaANS, and the cultivar AK showed a higher expression level of
      TaFNS gene during drought treatment. The increase rates of genes expression were
      superior in AK compared to CS. Total phenolics content, total flavonoids content,
      anthocyanin content, and schaftoside content in wheat leaves were enhanced during
      drought treatment and cultivar CS had a relative higher accumulation. These
      results suggest that the flavonoids pathway genes expression and accumulation of
      flavonoids compounds may be closely related to drought tolerant in wheat.
      Further, flavonoids response mechanism may be different between wheat cultivars.

PMID- 24727790
TI  - Alleviation of salt-induced photosynthesis and growth inhibition by salicylic
      acid involves glycinebetaine and ethylene in mungbean (Vigna radiata L.).
AB  - The influence of salicylic acid (SA) in alleviation of salt stress in mungbean
      (Vigna radiata L.) through modulation of glycinebetaine (GB) and ethylene was
      studied. SA application at 0.5 mM increased methionine (Met) and GB accumulation
      in plants concomitant with the suppression of ethylene formation by inhibiting 1
      aminocyclopropane carboxylic acid synthase (ACS) activity more conspicuously
      under salt stress than no stress. The increased GB accumulation together with
      reduced ethylene under salt stress by SA application was associated with
      increased glutathione (GSH) content and lower oxidative stress. These positive
      effects on plant metabolism induced by SA application led to improved
      photosynthesis and growth under salt stress. These results suggest that SA
      induces GB accumulation through increased Met and suppresses ethylene formation
      under salt stress and enhances antioxidant system resulting in alleviation of
      adverse effects of salt stress on photosynthesis and growth. These effects of SA
      were substantiated by the findings that application of SA-analogue, 2, 6,
      dichloro-isonicotinic acid (INA) and ethylene biosynthesis inhibitor,
      aminoethoxyvinylglycine (AVG) resulted in similar effects on Met, GB, ethylene
      production, photosynthesis and growth under salt stress. Future studies on the
      interaction between SA, GB and ethylene could be exploited for adaptive responses
      of plants under salt stress.

PMID- 24727791
TI  - Effects of exogenous 24-epibrassinolide on the photosynthetic membranes under non
      stress conditions.
AB  - In the present work the effects of exogenous 24-epibrassinolide (EBR) on
      functional and structural characteristics of the thylakoid membranes under non
      stress conditions were evaluated 48 h after spraying of pea plants with different
      concentrations of EBR (0.01, 0.1 and 1.0 mg.L(-1)). The results show that the
      application of 0.1 mg.L(-1) EBR has the most pronounced effect on the studied
      characteristics of the photosynthetic membranes. The observed changes in 540 nm
      light scattering and in the calorimetric transitions suggest alterations in the
      structural organization of the thylakoid membranes after EBR treatment, which in
      turn influence the kinetics of oxygen evolution, accelerate the electron
      transport rate, increase the effective quantum yield of photosystem II and the
      photochemical quenching. The EBR-induced changes in the photosynthetic membranes
      are most probably involved in the stress tolerance of plants.

PMID- 24727792
TI  - Expression of peanut Iron Regulated Transporter 1 in tobacco and rice plants
      confers improved iron nutrition.
AB  - Iron (Fe) limitation is a widespread agricultural problem in calcareous soils and
      severely limits crop production. Iron Regulated Transporter 1 (IRT1) is a key
      component for Fe uptake from the soil in dicot plants. In this study, the peanut
      (Arachis hypogaea L.) AhIRT1 was introduced into tobacco and rice plants using an
      Fe-deficiency-inducible artificial promoter. Induced expression of AhIRT1 in
      tobacco plants resulted in accumulation of Fe in young leaves under Fe deficient
      conditions. Even under Fe-excess conditions, the Fe concentration was also
      markedly enhanced, suggesting that the Fe status did not affect the uptake and
      translocation of Fe by AhIRT1 in the transgenic plants. Most importantly, the
      transgenic tobacco plants showed improved tolerance to Fe limitation in culture
      in two types of calcareous soils. Additionally, the induced expression of AhIRT1
      in rice plants also resulted in high tolerance to low Fe availability in
      calcareous soils.

PMID- 24727793
TI  - Photophysical and structural characterisation of in situ formed quantum dots.
AB  - Conjugated polymer-semiconductor quantum dot (QD) composites are attracting
      increasing attention due to the complementary properties of the two classes of
      materials. We report a convenient method for in situ formation of QDs, and
      explore the conditions required for light emission of nanocomposite blends. In
      particular we explore the properties of nanocomposites of the blue emitting
      polymer poly[9,9-bis(3,5-di-tert-butylphenyl)-9H-fluorene] together with cadmium
      sulphide (CdS) and cadmium selenide (CdSe) precursors. We show the formation of
      emissive quantum dots of CdSe from thermally decomposed precursor. The dots are
      formed inside the polymer matrix and have a photoluminescence quantum yield of
      7.5%. Our results show the importance of appropriate energy level alignment, and
      are relevant to the application of organic-inorganic systems in optoelectronic
      devices. 

PMID- 24727794
TI  - Natural killer cells induce eosinophil activation and apoptosis.
AB  - Eosinophils are potent inflammatory cells with numerous immune functions,
      including antigen presentation and exacerbation of inflammatory responses through
      their capacity to release a range of largely preformed cytokines and lipid
      mediators. Thus, timely regulation of eosinophil activation and apoptosis is
      crucial to develop beneficial immune response and to avoid tissue damage and
      induce resolution of inflammation. Natural Killer (NK) cells have been reported
      to influence innate and adaptive immune responses by multiple mechanisms
      including cytotoxicity against other immune cells. In this study, we analyzed the
      effect of the interaction between NK cells and eosinophils. Co-culture
      experiments revealed that human NK cells could trigger autologous eosinophil
      activation, as shown by up-regulation of CD69 and down-regulation of CD62L, as
      well as degranulation, evidenced by increased CD63 surface expression, secretion
      of eosinophil cationic protein (ECP) and eosinophil derived neurotoxin (EDN).
      Moreover, NK cells significantly and dose dependently increased eosinophil
      apoptosis as shown by annexin V and propidium iodide (PI) staining. Direct
      contact was necessary for eosinophil degranulation and apoptosis. Increased
      expression of phosphorylated extracellular signal-regulated kinase (ERK) in
      cocultured eosinophils and inhibition of eosinophil CD63 expression by
      pharmacologic inhibitors suggest that MAPK and PI3K pathways are involved in NK
      cell-induced eosinophil degranulation. Finally, we showed that NK cells increased
      reactive oxygen species (ROS) expression by eosinophils in co-culture and that
      mitochondrial inhibitors (rotenone and antimycin) partially diminished NK cell
      induced eosinophil apoptosis, suggesting the implication of mitochondrial ROS in
      NK cell-induced eosinophil apoptosis. Pan-caspase inhibitor (ZVAD-FMK) only
      slightly decreased eosinophil apoptosis in coculture. Altogether, our results
      suggest that NK cells regulate eosinophil functions by inducing their activation
      and their apoptosis. 

PMID- 24727795
TI  - Clinical and angiographic outcomes after intracoronary bare-metal stenting.
AB  - BACKGROUND: Data from a large patient population regarding very long-term
      outcomes after BMS implantation are inadequate. This study aimed to evaluate the
      very long-term (8-17 years) clinical and long-term (3-5 years) angiographic
      outcomes after intracoronary bare-metal stenting (BMS). METHODS AND RESULTS: From
      the Cardiovascular Atherosclerosis and Percutaneous TrAnsluminal INterventions
      (CAPTAIN) registry, a total of 2391 patients with 2966 lesions treated with 3190
      BMSs between November 1995 and May 2004 were evaluated. In total, 1898 patients
      with 2364 lesions, and 699 patients with 861 lesions underwent 6-month and 3- to
      5- year angiographic follow-up, respectively. During a mean follow-up period of
      149 +/- 51 months, 18.6% of the patients died (including 10.8% due to cardiac
      death), 6.1% developed reinfarction, 16.2% had target lesion revascularization
      (including 81% of the patients within the first year), 14.5% underwent new lesion
      stenting (including 72% of the patients after 3 years), 2.4% underwent coronary
      bypass surgery, and 1.6% had definite stent thrombosis. The overall
      cardiovascular event-free survival rate was 58.5%. The 6-month angiographic study
      indicated a 20% restenosis rate. The minimal luminal diameter increased from 0.65
      +/- 0.44 mm to 3.02 +/- 0.46 mm immediately after stenting, decreased to 2.06 +/-
      0.77 mm at the 6-month follow-up, and increased to 2.27 +/- 0.68 mm at the 3- to
      5-year follow-up. CONCLUSIONS: This study provides clinical and angiographic
      results from a large population of patients who underwent BMS implantations after
      a long-term follow-up period (149 +/- 51 months). The progression of coronary
      atherosclerosis developed over time, and presented with new lesion required stent
      implantation. The follow-up angiographic findings reconfirmed the late and
      sustained improvement in luminal diameter between 6 months and 3-5 years.

PMID- 24727796
TI  - FMRP regulates miR196a-mediated repression of HOXB8 via interaction with the AGO2
      MID domain.
AB  - Fragile X syndrome (FXS) is caused by the loss of expression of fragile X mental
      retardation protein (FMRP), a selective RNA-binding protein that negatively
      regulates mRNA substrates. FMRP can regulate the translation via the cross-talk
      with the miRNA machinery, but the functional association among FMRP, miRNAs and
      mutual target mRNAs has rarely been studied. In this research, we find that HOXB8
      mRNA is a target of FMRP associated with miR-196a-induced silencing, and discover
      that phosphorylation of FMRP promotes the miR-196a-mediated repression of HOXB8
      without affecting the interaction between FMRP and mRNA. We further identify that
      the FMRP-binding site involved in the miR-196a-mediated repression of HOXB8
      locates in the downstream neighbourhood of the miR-196a recognition element in
      the 3'UTR of HOXB8. Importantly, we reveal that FMRP faces toward the MID domain
      of AGO2 and interacts with a specific binding pocket (coordination with T544,
      K533 and K570) in the domain. Our research might provide new insights into both
      the cross-talk between FMRP and miRNA-mediated regulation of mRNA translation and
      the molecular pathogenesis of FXS.

PMID- 24727797
TI  - Dynamic and static measurement of interfacial capillary forces by a hybrid
      nanomechanical system.
AB  - The forces resulting from the presence of interfacial liquids have mechanical
      importance under ambient conditions. For holistic understanding of the liquid
      mediated interactions, we combine the force-gradient sensitivity of an atomic
      force microscope (AFM) with the force measuring capability of a micro
      electromechanical force sensor. Simultaneous measurement of the viscoelasticity
      of the water nanomeniscus and the absolute capillary force shows excellent
      agreement in its entire length, which justifies the validity of the widely used
      AFM results. We apply the hybrid system to measure the stress and strain, whose
      hysteretic response provides the intrinsic quantities of the liquid nanocluster. 

PMID- 24727798
TI  - A {0001} faceted single crystal NiS nanosheet electrocatalyst for dye-sensitised
      solar cells: sulfur-vacancy induced electrocatalytic activity.
AB  - Hydrothermally synthesised single crystal NiS nanosheets with an exposed (0001)
      surface exhibited a light conversion efficiency of 8.62% as an electrocatalyst
      for dye-sensitised solar cells (DSSCs), significantly higher than that of Pt
      based DSSCs (7.36%). The theoretical calculations revealed the exposed (0001)
      surface with superior catalytic activity owing to the existence of sulfur
      vacancies. 

PMID- 24727799
TI  - The long-term follow up of large-diameter Dacron(r) vascular grafts in surgical
      practice: a review.
AB  - Synthetic grafts have been widely used in cardiac and vascular surgery since the
      mid1970s. Considering the relative lack of randomized clinical trials or
      systematic analyses in the field of prosthetic large vessel diameter replacement,
      we reviewed the literature on the longterm performance and surgical management of
      complications of Dacron(r) grafts in both thoracic and abdominal aorta
      reconstruction and in the pediatric population. MedLine, Embase and Cochrane
      Library databases were searched for metaanalyses, reviews, clinical trials, and
      case reports pertinent to the study object.Aortic replacement with Dacron(r)
      prostheses is widely performed with acceptable outcome and a relatively low rate
      of graftrelated and postimplantation complications, such as rupture, infection
      and fistulization. However, progressive dilation and mechanical failure of the
      grafts represent the most worrisome complication in all the districts analyzed.
      The emerging concept of the mismatch in the biomechanical properties between the
      prosthetic material and native aorta is thought to be at the root of these
      complications leading to even more daunting consequences when the ascending aorta
      is involved. Indeed introduction of a noncompliant prosthesis in place of the
      native ascending aorta can exert detrimental effects not only at the level of the
      anastomosis, leading to pseudoaneurysm, but also can influence the optimal
      performance of the aortic root complex with consequent valve dysfunction and
      ventricular hypertrophy. Albeit confirming their overall successful performance,
      this review launches a warning on the current liberal use of noncompliant grafts
      in aortic position, remarking the need for alternative vascular conduits
      mimicking the native artery compliance.

PMID- 24727800
TI  - A streamlined system for species diagnosis in Caenorhabditis (Nematoda:
      Rhabditidae) with name designations for 15 distinct biological species.
AB  - The rapid pace of species discovery outstrips the rate of species description in
      many taxa. This problem is especially acute for Caenorhabditis nematodes, where
      the naming of distinct species would greatly improve their visibility and usage
      for biological research, given the thousands of scientists studying
      Caenorhabditis. Species description and naming has been hampered in
      Caenorhabditis, in part due to the presence of morphologically cryptic species
      despite complete biological reproductive isolation and often enormous molecular
      divergence. With the aim of expediting species designations, here we propose and
      apply a revised framework for species diagnosis and description in this group.
      Our solution prioritizes reproductive isolation over traditional morphological
      characters as the key feature in delineating and diagnosing new species,
      reflecting both practical considerations and conceptual justifications. DNA
      sequence divergence criteria help prioritize crosses for establishing patterns of
      reproductive isolation among the many species of Caenorhabditis known to science,
      such as with the ribosomal internal transcribed spacer-2 (ITS2) DNA barcode. By
      adopting this approach, we provide new species name designations for 15 distinct
      biological species, thus increasing the number of named Caenorhabditis species in
      laboratory culture by nearly 3-fold. We anticipate that the improved
      accessibility of these species to the research community will expand the
      opportunities for study and accelerate our understanding of diverse biological
      phenomena. 

PMID- 24727801
TI  - Whole-exome sequencing in familial atrial fibrillation.
AB  - AIMS: Positional cloning and candidate gene approaches have shown that atrial
      fibrillation (AF) is a complex disease with familial aggregation. Here, we
      employed whole-exome sequencing (WES) in AF kindreds to identify variants
      associated with familial AF. METHODS AND RESULTS: WES was performed on 18
      individuals in six modestly sized familial AF kindreds. After filtering very rare
      variants by multiple metrics, we identified 39 very rare and potentially
      pathogenic variants [minor allele frequency (MAF) <=0.04%] in genes not
      previously associated with AF. Despite stringent filtering >1 very rare variants
      in the 5/6 of the kindreds were identified, whereas no plausible variants
      contributing to familial AF were found in 1/6 of the kindreds. Two candidate AF
      variants in the calcium channel subunit genes (CACNB2 and CACNA2D4) were
      identified in two separate families using expression data and predicted function.
      CONCLUSION: By coupling family data with exome sequencing, we identified multiple
      very rare potentially pathogenic variants in five of six families, suggestive of
      a complex disease mechanism, whereas none were identified in the remaining AF
      pedigree. This study highlights some important limitations and challenges
      associated with performing WES in AF including the importance of having large
      well-curated multi-generational pedigrees, the issue of potential AF
      misclassification, and limitations of WES technology when applied to a complex
      disease.

PMID- 24727802
TI  - Light and electron microscopy of the European beaver (Castor fiber) stomach
      reveal unique morphological features with possible general biological
      significance.
AB  - Anatomical, histological, and ultrastructural studies of the European beaver
      stomach revealed several unique morphological features. The prominent attribute
      of its gross morphology was the cardiogastric gland (CGG), located near the
      oesophageal entrance. Light microscopy showed that the CGG was formed by
      invaginations of the mucosa into the submucosa, which contained densely packed
      proper gastric glands comprised primarily of parietal and chief cells. Mucous
      neck cells represented <0.1% of cells in the CGG gastric glands and 22-32% of
      cells in the proper gastric glands of the mucosa lining the stomach lumen. These
      data suggest that chief cells in the CGG develop from undifferentiated cells that
      migrate through the gastric gland neck rather than from mucous neck cells.
      Classical chief cell formation (i.e., arising from mucous neck cells) occurred in
      the mucosa lining the stomach lumen, however. The muscularis around the CGG
      consisted primarily of skeletal muscle tissue. The cardiac region was rudimentary
      while the fundus/corpus and pyloric regions were equally developed. Another
      unusual feature of the beaver stomach was the presence of specific mucus with a
      thickness up to 950 um (in frozen, unfixed sections) that coated the mucosa. Our
      observations suggest that the formation of this mucus is complex and includes the
      secretory granule accumulation in the cytoplasm of pit cells, the granule
      aggregation inside cells, and the incorporation of degenerating cells into the
      mucus. 

PMID- 24727803
TI  - The outcome of ipsilateral hemihepatectomy in mucin-producing bile duct tumors.
AB  - BACKGROUND: Mucin-producing bile duct tumors (MPBTs) are unusual, and we present
      our experience with nine surgically proven cases. METHODS: Between November 2002
      and November 2012, 9 patients with surgically proven MPBTs (including history of
      relevant hepatobiliary surgery in 6 patients) were encountered. Their clinical,
      imaging, and surgical findings were reviewed. RESULTS: The most common symptom is
      intermittent jaundice, which occurs in seven patients. The diagnostic specificity
      was 77.8% by preoperative Magnetic Resonance Cholangiopancreatography (MRCP). All
      the patients underwent ipsilateral hemihepatectomy or remnant hemihepatectomy,
      accompanied caudate lobectomy in one case and concomitant Roux-en-Y
      choledochojejunostomy in four cases. Postoperative course was uneventful. One
      patient, who had intra-abdominal recurrence 59 months after surgery, was received
      reoperation without recurrence at the last follow-up. The remaining eight
      patients were alive without disease recurrence. CONCLUSION: Based on our follow
      up of 9 cases that were surgically treated for MPBTs, we conclude that
      ipsilateral hemihepatectomy is a safe surgical procedure with an observed
      recurrence risk of 11.1% and all long-term survival.

PMID- 24727805
TI  - Dogaru et al. respond to "Does breastfeeding protect against 'asthma'?".

PMID- 24727804
TI  - Fusion transcript discovery in formalin-fixed paraffin-embedded human breast
      cancer tissues reveals a link to tumor progression.
AB  - The identification of gene fusions promises to play an important role in
      personalized cancer treatment decisions. Many rare gene fusion events have been
      identified in fresh frozen solid tumors from common cancers employing next
      generation sequencing technology. However the ability to detect transcripts from
      gene fusions in RNA isolated from formalin-fixed paraffin-embedded (FFPE) tumor
      tissues, which exist in very large sample repositories for which disease outcome
      is known, is still limited due to the low complexity of FFPE libraries and the
      lack of appropriate bioinformatics methods. We sought to develop a bioinformatics
      method, named gFuse, to detect fusion transcripts in FFPE tumor tissues. An
      integrated, cohort based strategy has been used in gFuse to examine single-end 50
      base pair (bp) reads generated from FFPE RNA-Sequencing (RNA-Seq) datasets
      employing two breast cancer cohorts of 136 and 76 patients. In total, 118 fusion
      events were detected transcriptome-wide at base-pair resolution across the 212
      samples. We selected 77 candidate fusions based on their biological relevance to
      cancer and supported 61% of these using TaqMan assays. Direct sequencing of 19 of
      the fusion sequences identified by TaqMan confirmed them. Three unique fused gene
      pairs were recurrent across the 212 patients with 6, 3, 2 individuals harboring
      these fusions respectively. We show here that a high frequency of fusion
      transcripts detected at the whole transcriptome level correlates with poor
      outcome (P<0.0005) in human breast cancer patients. This study demonstrates the
      ability to detect fusion transcripts as biomarkers from archival FFPE tissues,
      and the potential prognostic value of the fusion transcripts detected. 

PMID- 24727806
TI  - Recapture or precapture? Fallibility of standard capture-recapture methods in the
      presence of referrals between sources.
AB  - Capture-recapture methods, largely developed in ecology, are now commonly used in
      epidemiology to adjust for incomplete registries and to estimate the size of
      difficult-to-reach populations such as problem drug users. Overlapping lists of
      individuals in the target population, taken from administrative data sources, are
      considered analogous to overlapping "captures" of animals. Log-linear models,
      incorporating interaction terms to account for dependencies between sources, are
      used to predict the number of unobserved individuals and, hence, the total
      population size. A standard assumption to ensure parameter identifiability is
      that the highest-order interaction term is 0. We demonstrate that, when
      individuals are referred directly between sources, this assumption will often be
      violated, and the standard modeling approach may lead to seriously biased
      estimates. We refer to such individuals as having been "precaptured," rather than
      truly recaptured. Although sometimes an alternative identifiable log-linear model
      could accommodate the referral structure, this will not always be the case.
      Further, multiple plausible models may fit the data equally well but provide
      widely varying estimates of the population size. We demonstrate an alternative
      modeling approach, based on an interpretable parameterization and driven by
      careful consideration of the relationships between the sources, and we make
      recommendations for capture-recapture in practice. 

PMID- 24727807
TI  - Breastfeeding and childhood asthma: systematic review and meta-analysis.
AB  - Asthma and wheezing disorders are common chronic health problems in childhood.
      Breastfeeding provides health benefits, but it is not known whether or how
      breastfeeding decreases the risk of developing asthma. We performed a systematic
      review and meta-analysis of studies published between 1983 and 2012 on
      breastfeeding and asthma in children from the general population. We searched the
      PubMed and Embase databases for cohort, cross-sectional, and case-control
      studies. We grouped the outcomes into asthma ever, recent asthma, or recent
      wheezing illness (recent asthma or recent wheeze). Using random-effects meta
      analyses, we estimated pooled odds ratios of the association of breastfeeding
      with the risk for each of these outcomes. We performed meta-regression and
      stratified meta-analyses. We included 117 of 1,464 titles identified by our
      search. The pooled odds ratios were 0.78 (95% confidence interval: 0.74, 0.84)
      for 75 studies analyzing "asthma ever," 0.76 (95% confidence interval: 0.67,
      0.86) for 46 studies analyzing "recent asthma," and 0.81 (95% confidence
      interval: 0.76, 0.87) for 94 studies analyzing recent wheezing illness. After
      stratification by age, the strong protective association found at ages 0-2 years
      diminished over time. We found no evidence for differences by study design or
      study quality or between studies in Western and non-Western countries. A positive
      association of breastfeeding with reduced asthma/wheezing is supported by the
      combined evidence of existing studies.

PMID- 24727808
TI  - Invited commentary: Does breastfeeding protect against "asthma"?
AB  - Dogaru et al. have provided the best systematic review and meta-analysis to date
      of published studies of the association between breastfeeding and childhood
      asthma. Despite careful analysis of the reviewed studies' designs and
      methodological quality features, the authors are unable to explain the enormous
      heterogeneity (I(2) = 71%-92%) among the reported findings. This heterogeneity
      likely stems from the fact that "asthma" is a term used to denote a highly
      variable phenotype. The reasons for the protective association between
      breastfeeding and such a heterogeneous phenotype remain unclear, but may reflect
      nonblinding of feeding histories among observers who assess the outcome, as well
      as residual confounding, particularly by daycare attendance. The absence of a
      dose-response relationship based on breastfeeding duration or exclusivity also
      raises questions about the causal nature of the observed association. Future
      epidemiologic studies of asthma will require better and finer phenotyping to
      understand its etiology, including the potential protective effect of
      breastfeeding. 

PMID- 24727809
TI  - Me After You: Partner Influence and Individual Effort Predict Rejection of Self
      Aspects and Self-Concept Clarity After Relationship Dissolution.
AB  - Individuals in ongoing romantic relationships incorporate attributes from their
      partner into their own self-concepts. However, little research has investigated
      what happens to these attributes should the relationship end. Across three
      studies, the present research sought to examine factors that predicted whether
      individuals retain or reject attributes from their self-concept that they
      initially gained during a relationship. We predicted that individuals would be
      more likely to reject attributes from their self post-dissolution if their ex
      partner was influential in them adding those attributes to the self in the first
      place. However, we expected this effect to be moderated such that individuals who
      exerted greater, versus lesser, effort in maintaining relevant attributes would
      retain them as part of the self, regardless of whether the attribute originated
      from the partner. In addition, in two of our three studies, we explored the roles
      of partner influence, effort, and attribute rejection on individuals' post
      dissolution self-concept clarity.

PMID- 24727810
TI  - Attitude Certainty and Conflict Style: Divergent Effects of Correctness and
      Clarity.
AB  - Little research has examined the properties of people's attitudes that predict
      how they will respond to conflict with others whose opinions differ. We propose
      that one aspect of attitude certainty-attitude correctness, or the perception
      that one's attitude is the "right" attitude to have-will predict more competitive
      conflict styles. This hypothesis was tested across five data sets comprising four
      studies. In Studies 1a and 1b, perceptions of attitude correctness (but not
      another form of attitude certainty, attitude clarity) predicted participants'
      tendencies to send competitive messages to an ostensible partner who held the
      opposite opinion. In Studies 2 to 4, manipulations of attitude correctness, but
      not attitude clarity (Study 3), also increased competitiveness in conflict, and
      perceived correctness mediated the effect of the correctness manipulation on
      conflict style (Study 4). The present research has implications for both the
      predictors of conflict style and the consequences of different forms of attitude
      certainty.

PMID- 24727811
TI  - Fluctuation in Relationship Quality Over Time and Individual Well-Being: Main,
      Mediated, and Moderated Effects.
AB  - This study examined how the degree of within-person variation (or temporal
      fluctuation) in relationship quality over time was associated with well-being
      (psychological distress and life satisfaction). A national sample of 18- to 34
      year-old men and women in unmarried, opposite-sex relationships completed six
      waves of surveys every 4 months (N = 748). Controlling for initial levels of and
      linear changes in relationship quality, greater temporal fluctuation in
      relationship quality over time was associated with increasing psychological
      distress and decreasing life satisfaction over time. Decreased confidence in
      one's relationship partially mediated these associations. Moderation analyses
      revealed that the association between fluctuations in relationship quality and
      change in life satisfaction was stronger for women, participants cohabiting with
      their partners, and those with greater anxious attachment, whereas the
      association between fluctuations in relationship quality and change in
      psychological distress was stronger for people with greater avoidant attachment.

PMID- 24727812
TI  - My Mother and Me: Why Tiger Mothers Motivate Asian Americans But Not European
      Americans.
AB  - "Tiger Mother" Amy Chua provoked a culture clash with her claim that controlling
      parenting in Asian American (AA) contexts produces more successful children than
      permissive parenting in European American (EA) contexts. At the heart of this
      controversy is a difference in the normative models of self that guide behavior.
      Ideas and practices prevalent in AA contexts emphasize that the person is and
      should be interdependent with one's close others, especially one's mother. In
      contrast, EA contexts emphasize the person as independent, even from one's
      mother. We find that AA compared with EA high school students experience more
      interdependence with their mothers and pressure from them, but that the pressure
      does not strain their relationship with their mothers. Furthermore, following
      failure, AAs compared with EAs are more motivated by their mothers, and AAs are
      particularly motivated by pressure from their mothers when it conveys
      interdependence.

PMID- 24727813
TI  - Bone marrow mesenchymal stem cells from patients with aplastic anemia maintain
      functional and immune properties and do not contribute to the pathogenesis of the
      disease.
AB  - Aplastic anemia is a life-threatening bone marrow failure disorder characterized
      by peripheral pancytopenia and marrow hypoplasia. The majority of cases of
      aplastic anemia remain idiopathic, although hematopoietic stem cell deficiency
      and impaired immune responses are hallmarks underlying the bone marrow failure in
      this condition. Mesenchymal stem/stromal cells constitute an essential component
      of the bone marrow hematopoietic microenvironment because of their
      immunomodulatory properties and their ability to support hematopoiesis, and they
      have been involved in the pathogenesis of several hematologic malignancies. We
      investigated whether bone marrow mesenchymal stem cells contribute, directly or
      indirectly, to the pathogenesis of aplastic anemia. We found that mesenchymal
      stem cell cultures can be established from the bone marrow of aplastic anemia
      patients and display the same phenotype and differentiation potential as their
      counterparts from normal bone marrow. Mesenchymal stem cells from aplastic anemia
      patients support the in vitro homeostasis and the in vivo repopulating function
      of CD34(+) cells, and maintain their immunosuppressive and anti-inflammatory
      properties. These data demonstrate that bone marrow mesenchymal stem cells from
      patients with aplastic anemia do not have impaired functional and immunological
      properties, suggesting that they do not contribute to the pathogenesis of the
      disease. 

PMID- 24727814
TI  - Hepcidin levels in Diamond-Blackfan anemia reflect erythropoietic activity and
      transfusion dependency.

PMID- 24727815
TI  - Dexamethasone (6 mg/m2/day) and prednisolone (60 mg/m2/day) were equally
      effective as induction therapy for childhood acute lymphoblastic leukemia in the
      EORTC CLG 58951 randomized trial.
AB  - Dexamethasone could be more effective than prednisolone at similar anti
      inflammatory doses in the treatment of childhood acute lymphoblastic leukemia. In
      order to check if this "superiority" of dexamethasone might be dose-dependent, we
      conducted a randomized phase III trial comparing dexamethasone (6 mg/m(2)/day) to
      prednisolone (60 mg/m(2)/day) in induction therapy. All newly diagnosed children
      and adolescents with acute lymphoblastic leukemia in the 58951 EORTC trial were
      randomized on prephase day 1 or day 8. The main endpoint was event-free survival;
      secondary endpoints were overall survival and toxicity. A total of 1947 patients
      with acute lymphoblastic leukemia were randomized. At a median follow-up of 6.9
      years, the 8-year event-free survival rate was 81.5% in the dexamethasone arm and
      81.2% in the prednisolone arm; the 8-year overall survival rates were 87.2% and
      89.0% respectively. The 8-year incidences of isolated or combined central nervous
      system relapse were 2.9% and 4.5% in the dexamethasone and prednisolone arms,
      respectively. The incidence of grade 3-4 toxicities during induction and the
      frequency of osteonecrosis were similar in the two arms. In conclusion,
      dexamethasone and prednisolone, used respectively at the doses of 6 and 60
      mg/m(2)/day during induction, were equally effective and had a similar toxicity
      profile. Dexamethasone decreased the 8-year central nervous system relapse
      incidence by 1.6%. This trial was registered at www.clinicaltrials.gov as
      #NCT00003728. 

PMID- 24727816
TI  - Connective tissue growth factor is expressed in bone marrow stromal cells and
      promotes interleukin-7-dependent B lymphopoiesis.
AB  - Hematopoiesis occurs in a complex bone marrow microenvironment in which bone
      marrow stromal cells provide critical support to the process through direct cell
      contact and indirectly through the secretion of cytokines and growth factors. We
      report that connective tissue growth factor (Ctgf, also known as Ccn2) is highly
      expressed in murine bone marrow stromal cells. In contrast, connective tissue
      growth factor is barely detectable in unfractionated adult bone marrow cells.
      While connective tissue growth factor has been implicated in hematopoietic
      malignancies, and is known to play critical roles in skeletogenesis and
      regulation of bone marrow stromal cells, its role in hematopoiesis has not been
      described. Here we demonstrate that the absence of connective tissue growth
      factor in mice results in impaired hematopoiesis. Using a chimeric fetal liver
      transplantation model, we show that absence of connective tissue growth factor
      has an impact on B-cell development, in particular from pro-B to more mature
      stages, which is linked to a requirement for connective tissue growth factor in
      bone marrow stromal cells. Using in vitro culture systems, we demonstrate that
      connective tissue growth factor potentiates B-cell proliferation and promotes pro
      B to pre-B differentiation in the presence of interleukin-7. This study provides
      a better understanding of the functions of connective tissue growth factor within
      the bone marrow, showing the dual regulatory role of the growth factor in
      skeletogenesis and in stage-specific B lymphopoiesis. 

PMID- 24727817
TI  - Detection and outcome of occult leptomeningeal disease in diffuse large B-cell
      lymphoma and Burkitt lymphoma.
AB  - The benefit of intrathecal therapy and systemic rituximab on the outcome of
      diffuse large B-cell lymphoma at risk of central nervous system disease is
      controversial. Furthermore, the effect of intrathecal treatment and rituximab in
      diffuse large B-cell and Burkitt lymphoma with occult leptomeningeal disease
      detected by flow cytometry at diagnosis is unknown. Untreated diffuse large B
      cell (n=246) and Burkitt (n=80) lymphoma at clinical risk of central nervous
      system disease and having had pre-treatment cerebrospinal fluid were analyzed by
      flow cytometry and cytology. Spinal fluid involvement was detected by flow
      cytometry alone (occult) in 33 (13%) diffuse large B-cell and 9 (11%) Burkitt
      lymphoma patients, and detected by cytology in 11 (4.5%) and 5 (6%) patients,
      respectively. Diffuse large B-cell lymphoma with occult spinal fluid involvement
      had poorer survival (P=0.0001) and freedom from central nervous system relapse
      (P<0.0001) compared to negative cases. Burkitt lymphoma with occult spinal fluid
      involvement had an inferior freedom from central nervous system relapse (P=0.026)
      but not survival. The amount of intrathecal chemotherapy was quantitatively
      associated with survival in diffuse large B-cell lymphoma with (P=0.02) and
      without (P=0.001) occult spinal fluid involvement. However, progression of
      systemic disease and not control of central nervous system disease was the
      principal cause of treatment failure. In diffuse large B-cell lymphoma, systemic
      rituximab was associated with improved freedom from central nervous system
      relapse (P=0.003) but not with survival. Our results suggest that patients at
      risk of central nervous system disease should be evaluated by flow cytometry and
      that intrathecal prophylaxis/therapy is beneficial. 

PMID- 24727818
TI  - Pediatric posttransplant relapsed/refractory B-precursor acute lymphoblastic
      leukemia shows durable remission by therapy with the T-cell engaging bispecific
      antibody blinatumomab.
AB  - We report on posttransplant relapsed pediatric patients with B-precursor acute
      lymphoblastic leukemia with no further standard of care therapy who were treated
      with the T-cell engaging CD19/CD3-bispecific single-chain antibody construct
      blinatumomab on a compassionate use basis. Blast load was assessed prior to,
      during and after blinatumomab cycle using flow cytometry to detect minimal
      residual disease, quantitative polymerase chain reaction for rearrangements of
      the immunoglobulin or T-cell receptor genes, and bcr/abl mutation detection in
      one patient with Philadelphia chromosome-positive acute lymphoblastic leukemia.
      Blinatumomab was administered as a 4-week continuous intravenous infusion at a
      dosage of 5 or 15 MUg/m(2)/day. Nine patients received a total of 18 cycles. Four
      patients achieved complete remission after the first cycle of treatment; 2
      patients showed a complete remission from the second cycle after previous
      reduction of blast load by chemotherapy. Three patients did not respond, of whom
      one patient proceeded to a second cycle without additional chemotherapy and again
      did not respond. Four patients were successfully retransplanted in molecular
      remission from haploidentical donors. After a median follow up of 398 days, the
      probability of hematologic event-free survival is 30%. Major toxicities were
      grade 3 seizures in one patient and grade 3 cytokine release syndrome in 2
      patients. Blinatumomab can induce molecular remission in pediatric patients with
      posttransplant relapsed B-precursor acute lymphoblastic leukemia and facilitate
      subsequent allogeneic hematopoietic stem cell transplantation from haploidentical
      donor with subsequent long-term leukemia-free survival. 

PMID- 24727819
TI  - Investigating the real role of HIF-1 and HIF-2 in iron recycling by macrophages.

PMID- 24727820
TI  - Age is a prognostic factor even among patients with multiple myeloma younger than
      66 years treated with high-dose melphalan: the IFM experience on 2316 patients.
AB  - Age is a strong prognostic factor in multiple myeloma. The overall survival is
      shorter in patients older than 66 years, and even shorter in those older than 75
      years. Whether age is also a prognostic parameter in patients younger than 66
      years treated homogeneously with intensive approaches is unknown. To address this
      issue, we retrospectively analyzed a series of 2316 patients treated
      homogeneously with 3-4 cycles of induction chemotherapy followed by a high-dose
      melphalan course, without any consolidation or maintenance. We show that patients
      older than 60 years have a statistically significant shorter overall survival.
      The analysis of prognostic parameters did not show a higher incidence of high
      risk cytogenetics, but a higher incidence of International Staging System (ISS)
      stages 2 and 3, mainly due to higher beta2-microglobulin levels. This study is
      the first to demonstrate the impact of age in the outcome of 'young' patients
      with multiple myeloma, and suggests that this parameter should be included in the
      stratification factors for future prospective clinical trials. 

PMID- 24727821
TI  - Red blood cell immunization in sickle cell disease: evidence of a large responder
      group and a low rate of anti-Rh linked to partial Rh phenotype.

PMID- 24727822
TI  - Choroidal thickness, age, and refractive error in healthy Korean subjects.
AB  - PURPOSE: To investigate choroidal thickness (CT) in healthy Korean subjects
      measured by enhanced depth imaging optical coherence tomography and its
      association with age, axial length, and refractive error. METHODS: Choroidal
      scans using enhanced depth imaging optical coherence tomography in each eye of
      286 healthy eyes were obtained at the macula. Choroidal thickness was measured at
      the fovea. Two separate line scans were obtained (one horizontal and one
      vertical). RESULTS: The mean (+/-SD) age was 40.18 (+/-17.89) years (range, 13 to
      75 years). The mean (+/-SD) subfoveal CT was 307.26 (+/-95.18) MUm. Multivariable
      linear regression suggested that age and refractive error were the most
      significant factors associated with subfoveal CT (all p < 0.0001) with an
      adjusted R = 0.181. In subjects younger than 60 years, refractive error or axial
      length and age retained statistically significant correlation with subfoveal CT,
      whereas such a relationship was lost in subjects older than 60 years.
      CONCLUSIONS: The mean subfoveal CT measurement showed the most significant
      positive correlation with refractive error and the most significant negative
      correlation with age. For patients younger than 60 years, there was a significant
      correlation of subfoveal CT with age and refractive error or axial length,
      whereas such significant association was not observed in subjects older than 60
      years.

PMID- 24727823
TI  - Squinting and photophobia in intermittent exotropia.
AB  - PURPOSE: To report factors associated with preoperative squinting, defined as
      transient eye closure in bright light, and photophobia and the factors affecting
      improvement of these symptoms postoperatively in intermittent exotropia. METHODS:
      In this retrospective study, patients (N = 99) were divided into groups according
      to the presence (n = 54) or absence (n = 45) of preoperative squinting and the
      presence (n = 64) or absence (n = 35) of photophobia. Clinical characteristics,
      including overaction or underaction of the oblique muscle and fundus intorsion
      and extorsion, were compared between the two groups. The squinting and
      photophobia groups were further categorized into two subgroups each according to
      postoperative improvement. The extended list of characteristics, including the
      duration from onset to surgery, postoperative angle of deviation, and fusion, was
      compared between the two subgroups. RESULTS: Preoperatively, 54 (54.5%) and 64
      (64.6%) patients had squinting and photophobia, respectively. The coincidence of
      squinting and photophobia was marginally significant (p = 0.05). Postoperatively,
      squinting and photophobia disappeared in 64.8 and 59.4% of the patients,
      respectively. The photophobia group had a younger onset age of strabismus than
      the nonphotophobia group (39.3 vs. 56.4 months; p = 0.03). Good fusional status
      at the near range was more common in the nonsquinting group than in the squinting
      group (74.3 vs. 47.6%; p = 0.02). Superior oblique overaction was significantly
      more common in the squinting group than in the nonsquinting group (11.1 vs. 0%; p
      = 0.03). Early surgical correction and successful outcomes were associated with
      squinting improvement (p = 0.001 and p = 0.02, respectively). CONCLUSIONS: More
      than 50% of patients with intermittent exotropia had squinting or photophobia,
      and approximately 60% of symptomatic patients experienced improvement
      postoperatively. The onset of strabismus, near fusion, superior oblique
      overaction, and fundus intorsion were related to these symptoms. Early surgery
      and successful eye position realignment were beneficial for improving squinting
      postoperatively.

PMID- 24727824
TI  - Relationship between macular bending and foveoschisis in myopic patients.
AB  - PURPOSE: To investigate factors associated with myopic foveoschisis and macular
      bending and to determine how the presence of macular bending affects the
      development of myopic foveoschisis. METHODS: In a prospective study of 194 eyes
      of 105 patients with high myopia, we performed complete ophthalmic examinations,
      optical coherence tomography (OCT), and A-scan ultrasounds. Patients were divided
      into three groups according to the OCT results. Group 1 consisted of 25 eyes (17
      patients) with myopic foveoschisis; group 2 consisted of 36 eyes (20 patients)
      with macular bending; and group 3 consisted of 135 eyes (68 patients) without
      macular bending, foveoschisis, or other diseases. Macular bending was defined as
      a smooth macular elevation observed upon OCT in patients with pathologic myopia.
      Age, sex, spherical equivalence, axial length (AXL), and OCT findings were
      obtained and compared to identify factors that are related to myopic foveoschisis
      and macular bending. Moreover, using the whole data set, we evaluated and
      correlated myopic foveoschisis with the presence or absence of macular bending to
      determine whether this bulge in the macular area influences the development of
      myopic foveoschisis. RESULTS: In group 1, all eyes presented posterior staphyloma
      and two factors were independently associated with a higher risk of having myopic
      foveoschisis: internal limiting membrane detachment (p < 0.001) and retinal
      arteriolar traction (p < 0.001). In group 2, only retinal arteriolar traction (p
      < 0.009) was independently associated with macular bending. Furthermore, macular
      bending was significantly correlated as a protective factor against myopic
      foveoschisis (adjusted odds ratio, 0.116; 95% confidence interval, 0.019 to
      0.701; p < 0.019); the AXL of patients with the same spherical equivalence and
      macular bending was significantly shorter than that of patients without macular
      bending (p = 0.005). CONCLUSIONS: Intraocular and extraocular wall factors were
      associated with myopic traction maculopathy, which plays an important role in its
      pathogenesis. Moreover, macular bending might be a key factor in preventing
      myopic foveoschisis by decreasing AXL.

PMID- 24727826
TI  - Between-subject variability in asymmetry analysis of macular thickness.
AB  - PURPOSE: To investigate the use of asymmetry analysis to reduce between-subject
      variability of macular thickness measurements using spectral domain optical
      coherence tomography. METHODS: Sixty-three volunteers (33 young subjects [aged 21
      to 35 years] and 30 older subjects [aged 45 to 85 years]) free of eye disease
      were recruited. Macular images were gathered with the Spectralis optical
      coherence tomography. An overlay 24- by 24-degree grid was divided into five
      zones per hemifield, and asymmetry analysis was computed as the difference
      between superior and inferior zone thicknesses. We hypothesized that the lowest
      variation and the highest density of ganglion cells will be found approximately 3
      to 6 degrees from the foveola, corresponding to zones 1 and 2. For each zone and
      age group, between-subject SDs were compared for retinal thickness versus
      asymmetry analysis using an F test. To account for repeated comparisons, p <
      0.0125 was required for statistical significance. Axial length and corneal
      curvature were measured with an IOLMaster. RESULTS: For OD, asymmetry analysis
      reduced between-subject variability in zones 1 and 2 in both groups (F > 3.2, p <
      0.001). Standard deviation for zone 1 dropped from 12.0 to 3.0 MUm in the young
      group and from 11.7 to 2.6 MUm in the older group. Standard deviation for zone 2
      dropped from 13.6 to 5.3 MUm in the young group and from 11.1 to 5.8 MUm in the
      older group. Combining all subjects, neither retinal thickness nor asymmetry
      analysis showed a strong correlation with axial length or corneal curvature (R2 <
      0.01). Analysis for OS yielded the same pattern of results, as did asymmetry
      analyses between eyes (F > 3.8, p < 0.0001). CONCLUSIONS: Asymmetry analysis
      reduced between-subject variability in zones 1 and 2. Combining the five zones
      together produced a higher between-subject variation of the retinal thickness
      asymmetry analysis; thus, we encourage clinicians to be cautious when
      interpreting the asymmetry analysis printouts.

PMID- 24727827
TI  - Visual field coordinates of pupillary circular axis and optical axis.
AB  - PURPOSE: We term the visual field position from which the pupil appears most
      nearly circular as the pupillary circular axis (PCAx). The aim was to determine
      and compare the horizontal and vertical coordinates of the PCAx and optical axis
      from pupil shape and refraction information for only the horizontal meridian of
      the visual field. METHODS: The PCAx was determined from the changes with visual
      field angle in the ellipticity and orientation of pupil images out to +/-90
      degrees from fixation along the horizontal meridian for the right eyes of 30
      people. This axis was compared with the optical axis determined from the changes
      in the astigmatic components of the refractions for field angles out to +/-35
      degrees in the same meridian. RESULTS: The mean estimated horizontal and vertical
      field coordinates of the PCAx were -5.3 (+/-1.9) and -3.2 (+/-1.5) degrees
      compared with -4.8 (+/-5.1) and -1.5 (+/-3.4) degrees for the optical axis,
      respectively. The vertical coordinates of the two axes were just significantly
      different (p = 0.03), but there was no significant correlation between them. Only
      the horizontal coordinate of the PCAx was significantly related to the refraction
      in the group. CONCLUSIONS: On average, the PCAx is displaced from the line-of
      sight by about the same angle as the optical axis, but there is more intersubject
      variation in the position of the optical axis. When modeling the optical
      performance of the eye, it appears reasonable to assume that the pupil is
      circular when viewed along the line-of-sight.

PMID- 24727825
TI  - Risk factors for astigmatism in the Vision in Preschoolers Study.
AB  - PURPOSE: To determine demographic and refractive risk factors for astigmatism in
      the Vision in Preschoolers Study. METHODS: Three- to 5-year-old Head Start
      preschoolers (N = 4040) from five clinical centers underwent comprehensive eye
      examinations by study-certified optometrists and ophthalmologists, including
      monocular visual acuity testing, cover testing, and cycloplegic retinoscopy.
      Astigmatism was defined as the presence of greater than or equal to +1.5 diopters
      (D) cylinder in either eye, measured with cycloplegic refraction. The
      associations of risk factors with astigmatism were evaluated using the odds ratio
      (OR) and its 95% confidence interval (CI) from logistic regression models.
      RESULTS: Among 4040 Vision in Preschoolers Study participants overrepresenting
      children with vision disorders, 687 (17%) had astigmatism, and most (83.8%) had
      with-the-rule astigmatism. In multivariate analyses, African American (OR, 1.65;
      95% CI, 1.22 to 2.24), Hispanic (OR, 2.25; 95% CI, 1.62 to 3.12), and Asian (OR,
      1.76; 95% CI, 1.06 to 2.93) children were more likely to have astigmatism than
      non-Hispanic white children, whereas American Indian children were less likely to
      have astigmatism than Hispanic, African American, and Asian children (p <
      0.0001). Refractive error was associated with astigmatism in a nonlinear manner,
      with an OR of 4.50 (95% CI, 3.00 to 6.76) for myopia (<=-1.0 D in spherical
      equivalent) and 1.55 (95% CI, 1.29 to 1.86) for hyperopia (>=+2.0 D) when
      compared with children without refractive error (>-1.0 D, <+2.0 D). There was a
      trend of an increasing percentage of astigmatism among older children (linear
      trend p = 0.06). The analysis for risk factors of with-the-rule astigmatism
      provided similar results. CONCLUSIONS: Among Head Start preschoolers, Hispanic,
      African American, and Asian race as well as myopic and hyperopic refractive error
      were associated with an increased risk of astigmatism, consistent with findings
      from the population-based Multi-ethnic Pediatric Eye Disease Study and the
      Baltimore Pediatric Eye Disease Study. American Indian children had lower risk of
      astigmatism.

PMID- 24727828
TI  - High-frequency jet ventilation shortened the duration of gas embolization during
      laparoscopic liver resection in a porcine model.
AB  - BACKGROUND: Positive pressure mechanical ventilation causes rhythmic changes in
      thoracic pressure and central blood flow. If entrainment occurs, it could be
      easier for carbon dioxide to enter through a wounded vein during laparoscopic
      liver lobe resection (LLR). High-frequency jet ventilation (HFJV) is a
      ventilating method that does not cause pronounced pressure or blood flow changes.
      This study aimed to investigate whether HFJV could influence the frequency,
      severity, or duration of gas embolism (GE) during LLR. METHODS: Twenty-four
      anaesthetized piglets underwent lobe resection and were randomly assigned to
      either normal frequency ventilation (NFV) or HFJV (n=12 per group). During
      resection, a standardized injury to the left hepatic vein was created to increase
      the risk of GE. Haemodynamic and respiratory variables were monitored. Online
      blood gas monitoring and transoesophageal echocardiography were used. GE
      occurrence and severity were graded as 0 (none), 1 (minor), or 2 (major),
      depending on the echocardiography results. RESULTS: GE duration was shorter in
      the HFJV group (P=0.008). However, no differences were found between the two
      groups in the frequency or severity of embolism. Incidence of Grade 2 embolism
      was less than that found in previous studies and physiological responses to
      embolism were variable. CONCLUSION: HFJV shortened the mean duration of GE during
      LLR and was a feasible ventilation method during the procedure. Individual
      physiological responses to GE were unpredictable.

PMID- 24727829
TI  - Systematic review and meta-analysis of the effect of intraoperative alpha2
      adrenergic agonists on postoperative behaviour in children.
AB  - Undergoing general anaesthesia is distressing for children, with up to two-thirds
      demonstrating abnormal behaviours after their procedure, such as emergence
      delirium (ED) and post-hospitalization behaviour change. The aim of this
      systematic review was to determine the effect of intraoperative i.v. alpha2
      adrenergic agonists on postoperative behaviour in children. We included published
      full-text reports of randomized controlled trials involving children who received
      i.v. clonidine or dexmedetomidine after induction of general anaesthesia, who
      were assessed for postoperative behavioural disturbance. After screening of
      references identified by the search strategy, a data collection form was
      developed and piloted. Data extraction was performed by one reviewer and checked
      by a second. Twelve randomized trials met the inclusion criteria. Ten studies
      (n=669) reported dichotomous data that were included in the pooled analysis of
      alpha2-adrenergic agonists vs placebo. There was strong evidence that i.v. alpha2
      adrenergic agonists reduced postoperative ED (overall summary odds ratio 0.28,
      95% confidence interval 0.19-0.40, P<0.001). No studies examined post
      hospitalization negative behaviour changes. There was evidence that alpha2
      adrenergic agonists prolonged time in the recovery room. No adverse haemodynamic
      events were reported in any arm of any study. This meta-analysis provides
      evidence that intraoperative i.v. alpha2-adrenergic agonists reduce the incidence
      of emergency delirium in children. The prolongation of time in recovery is
      unlikely to be clinically relevant. The absence of data regarding the effect on
      post-hospitalization behavioural changes provides an opportunity for future
      research.

PMID- 24727831
TI  - Nonvolatile memory effects in an orthoconic smectic liquid crystal mixture doped
      with polymer-capped gold nanoparticles.
AB  - Promising applications of liquid crystal nanocomposites have driven extensive
      efforts to achieve non-volatile memory effects for the realization of electronic
      storage devices. In this context, non-volatile memory effects in an orthoconic
      smectic liquid crystal mixture, with and without polymer capped gold
      nanoparticles, were investigated. The dielectric spectroscopy technique was
      performed by applying a d.c. bias during the measurement or a d.c. potential
      before the start of the measurement in order to obtain pre-conditioning of the
      sample. Both techniques showed the presence of non-volatile memory effects in the
      pure orthoconic smectic liquid crystal mixture similar to the doped one. The
      results demonstrate that the addition of gold nanoparticles enhances the memory
      effect making it permanent. Our experimental evidence underlines the importance
      of the structure of the host liquid crystal and clearly suggests that the
      prolonged time memory effect, observed in the doped liquid crystal, is due to the
      electric field inducing charge transfer from the liquid crystal molecules to the
      gold nanoparticles, thanks to the polymer-capping which acts as an ionic charge
      trapper. Such an ionic trap effect is also responsible for strong reduction of
      total conductivity of the doped system. 

PMID- 24727830
TI  - Structural mechanism of the dynein power stroke.
AB  - Dyneins are large microtubule motor proteins required for mitosis, intracellular
      transport and ciliary and flagellar motility. They generate force through a power
      stroke mechanism, which is an ATP-consuming cycle of pre- and post-power-stroke
      conformational changes that cause relative motion between different dynein
      domains. However, key structural details of dynein's force generation remain
      elusive. Here, using cryo-electron tomography of intact, active (that is,
      beating), rapidly frozen sea urchin sperm flagella, we determined the in situ
      three-dimensional structures of all domains of both pre- and post-power-stroke
      dynein, including the previously unresolved linker and stalk of pre-power-stroke
      dynein. Our results reveal that the rotation of the head relative to the linker
      is the key action in dynein movement, and that there are at least two distinct
      pre-power-stroke conformations: pre-I (microtubule-detached) and pre-II
      (microtubule-bound). We provide three-dimensional reconstructions of native
      dyneins in three conformational states, in situ, allowing us to propose a
      molecular model of the structural cycle underlying dynein movement.

PMID- 24727832
TI  - Severe acute otitis media caused by mucoid Streptococcus pyogenes in a previously
      healthy adult.
AB  - Streptococcus (S.) pyogenes is well recognized as the most common pathogen
      causing pharyngotonsillitis in school-age children. In Japan, mucoid
      Streptococcus pneumoniae is well known as a causative agent of severe acute
      otitis media (AOM); however, mucoid S. pyogenes has rarely been reported. To the
      best of our knowledge, this is the first report of an AOM patient caused by
      mucoid S. pyogenes in Japan. A 36-year-old previously healthy female was referred
      to our hospital with suspicion of cerebrospinal otorrhea due to increasing
      otalgia accompanied by headache following myringotomy. Bacterial cultures of
      middle ear secretions were performed, and mucoid-form colonies surrounded by
      zones of complete beta-hemolysis were produced on sheep's blood agar. Antigen
      agglutination test results were positive for S. pyogenes, and thus the patient
      received treatment with panipenem-betamipron 2.0 g/day for 10 days, which
      resolved nearly all symptoms. The bacteriological features of this strain were
      then investigated. The M-protein genotype encoded by the emm gene, the major
      virulence factor of S. pyogenes, was determined to be emm75. Generally, S.
      pyogenes forms colonies having non-mucoid matt appearances based on beta
      hemolysis of sheep's blood agar. The mucoid phenotype results from abundant
      production of hyaluronic acid capsular polysaccharide, a key virulence
      determinant. emm75 is common in noninvasive, but less common in invasive disease.
      In conclusion, mucoid S. pyogenes can cause severe infection even in previously
      healthy persons. Emergence of mucoid S. pyogenes and drug resistance trends
      should be monitored in the future. 

PMID- 24727833
TI  - Three-dimensional in vitro cancer models: a short review.
AB  - The re-creation of the tumor microenvironment including tumor-stromal
      interactions, cell-cell adhesion and cellular signaling is essential in cancer
      related studies. Traditional two-dimensional (2D) cell culture and animal models
      have been proven to be valid in some areas of explaining cancerous cell behavior
      and interpreting hypotheses of possible mechanisms. However, a well-defined three
      dimensional (3D) in vitro cancer model, which mimics tumor structures found in
      vivo and allows cell-cell and cell-matrix interactions, has gained strong
      interest for a wide variety of diagnostic and therapeutic applications. This
      communication attempts to provide a representative overview of applying 3D in
      vitro biological model systems for cancer related studies. The review compares
      and comments on the differences in using 2D models, animal models and 3D in vitro
      models for cancer research. Recent technologies to construct and develop 3D in
      vitro cancer models are summarized in aspects of modeling design, fabrication
      technique and potential application to biology, pathogenesis study and drug
      testing. With the help of advanced engineering techniques, the development of a
      novel complex 3D in vitro cancer model system will provide a better opportunity
      to understand crucial cancer mechanisms and to develop new clinical therapies.

PMID- 24727834
TI  - Strategies for high-performance resource-efficient compression of neural spike
      recordings.
AB  - Brain-machine interfaces (BMIs) based on extracellular recordings with
      microelectrodes provide means of observing the activities of neurons that
      orchestrate fundamental brain function, and are therefore powerful tools for
      exploring the function of the brain. Due to physical restrictions and risks for
      post-surgical complications, wired BMIs are not suitable for long-term studies in
      freely behaving animals. Wireless BMIs ideally solve these problems, but they
      call for low-complexity techniques for data compression that ensure maximum
      utilization of the wireless link and energy resources, as well as minimum heat
      dissipation in the surrounding tissues. In this paper, we analyze the
      performances of various system architectures that involve spike detection, spike
      alignment and spike compression. Performance is analyzed in terms of spike
      reconstruction and spike sorting performance after wireless transmission of the
      compressed spike waveforms. Compression is performed with transform coding, using
      five different compression bases, one of which we pay special attention to. That
      basis is a fixed basis derived, by singular value decomposition, from a large
      assembly of experimentally obtained spike waveforms, and therefore represents a
      generic basis specially suitable for compressing spike waveforms. Our results
      show that a compression factor of 99.8%, compared to transmitting the raw
      acquired data, can be achieved using the fixed generic compression basis without
      compromising performance in spike reconstruction and spike sorting. Besides
      illustrating the relative performances of various system architectures and
      compression bases, our findings show that compression of spikes with a fixed
      generic compression basis derived from spike data provides better performance
      than compression with downsampling or the Haar basis, given that no optimization
      procedures are implemented for compression coefficients, and the performance is
      similar to that obtained when the optimal SVD based basis is used. 

PMID- 24727836
TI  - Maternal pre-pregnancy BMI and intelligence quotient (IQ) in 5-year-old children:
      a cohort based study.
AB  - BACKGROUND: An association between maternal pre-pregnancy BMI and childhood
      intelligence quotient (IQ) has repeatedly been found but it is unknown if this
      association is causal or due to confounding caused by genetic or social factors.
      METHODS: We used a cohort of 1,783 mothers and their 5-year-old children sampled
      from the Danish National Birth Cohort. The children participated between 2003 and
      2008 in a neuropsychological assessment of cognitive ability including IQ tests
      taken by both the mother and the child. Linear regression analyses were used to
      estimate the associations between parental BMI and child IQ adjusted for a
      comprehensive set of potential confounders. Child IQ was assessed with the
      Wechsler Primary and Preschool Scales of Intelligence--Revised (WPPSI-R).
      RESULTS: The crude association between maternal BMI and child IQ showed that BMI
      was adversely associated with child IQ with a reduction in IQ of -0.40 point for
      each one unit increase in BMI. This association was attenuated after adjustment
      for social factors and maternal IQ to a value of -0.27 (-0.50 to -0.03). After
      mutual adjustment for the father's BMI and all other factors except maternal IQ,
      the association between paternal BMI and child IQ yielded a regression
      coefficient of -0.26 (-0.59 to 0.07), which was comparable to that seen for
      maternal BMI (-0.20 (-0.44 to 0.04)). CONCLUSION: Although maternal pre-pregnancy
      BMI was inversely associated with the IQ of her child, the similar association
      with paternal BMI suggests that it is not a specific pregnancy related adiposity
      effect.

PMID- 24727835
TI  - Crystal structure of ATP-bound Get3-Get4-Get5 complex reveals regulation of Get3
      by Get4.
AB  - Correct localization of membrane proteins is essential to all cells. Chaperone
      cascades coordinate the capture and handover of substrate proteins from the
      ribosomes to the target membranes, yet the mechanistic and structural details of
      these processes remain unclear. Here we investigate the conserved GET pathway, in
      which the Get4-Get5 complex mediates the handover of tail-anchor (TA) substrates
      from the cochaperone Sgt2 to the Get3 ATPase, the central targeting factor. We
      present a crystal structure of a yeast Get3-Get4-Get5 complex in an ATP-bound
      state and show how Get4 primes Get3 by promoting the optimal configuration for
      substrate capture. Structure-guided biochemical analyses demonstrate that Get4
      mediated regulation of ATP hydrolysis by Get3 is essential to efficient TA
      protein targeting. Analogous regulation of other chaperones or targeting factors
      could provide a general mechanism for ensuring effective substrate capture during
      protein biogenesis.

PMID- 24727838
TI  - Does rituximab help patients with primary Sjogren syndrome?

PMID- 24727837
TI  - Comparable ascertainment of newly-diagnosed atrial fibrillation using active
      cohort follow-up versus surveillance of centers for medicare and medicaid
      services in the atherosclerosis risk in communities study.
AB  - OBJECTIVE: Increasingly, epidemiologic studies use administrative data to
      identify atrial fibrillation (AF). Capture of incident AF is not well documented.
      We examined incidence rates and concordance of AF diagnosis based on active
      cohort follow-up versus surveillance of Centers for Medicare and Medicaid
      Services data in the Atherosclerosis Risk in Communities study. METHODS:
      Atherosclerosis Risk in Communities cohort participants without prevalent AF
      enrolled in fee-for-service Medicare, with inpatient and outpatient coverage, for
      at least 12 continuous months between 1991 and 2009 were included. In active
      Atherosclerosis Risk in Communities study follow-up, annual telephone calls
      captured hospitalizations and deaths with incident AF diagnosis codes. For
      Centers for Medicare and Medicaid Services data, incident AF was defined by
      billed inpatient and outpatient diagnoses. RESULTS: Of 10,134 eligible cohort
      participants, 738 developed AF according to both Atherosclerosis Risk in
      Communities and Centers for Medicare and Medicaid Services data; an additional 93
      and 288 incident cases were identified using only Atherosclerosis Risk in
      Communities and Centers for Medicare and Medicaid Services data, respectively.
      Incidence rates per 1,000 person-years were 10.8 (95% confidence interval: 10.1
      11.6) and 13.6 (95% confidence interval: 12.8-14.4) in Atherosclerosis Risk in
      Communities and Centers for Medicare and Medicaid Services, respectively;
      agreement was 96%; kappa was 0.77 (95% confidence interval: 0.75-0.80). Earlier
      AF ascertainment by one system versus the other was not associated with any
      cardiovascular disease risk factors, after accounting for sociodemographic
      factors. Additional Centers for Medicare and Medicaid Services events did not
      alter observed associations between risk factors and AF. CONCLUSION: Among fee
      for-service enrollees, AF incidence rates were slightly lower for active cohort
      follow-up than for Centers for Medicare and Medicaid Services surveillance,
      because the latter included outpatient atrial fibrillation. Concordance was high
      and combining the two approaches could provide a more complete picture of newly
      diagnosed AF.

PMID- 24727839
TI  - Microsporidiosis acquired through solid organ transplantation: a public health
      investigation.
AB  - BACKGROUND: Encephalitozoon cuniculi, a microsporidial species most commonly
      recognized as a cause of renal, respiratory, and central nervous system
      infections in immunosuppressed patients, was identified as the cause of a
      temporally associated cluster of febrile illness among 3 solid organ transplant
      recipients from a common donor. OBJECTIVE: To confirm the source of the illness,
      assess donor and recipient risk factors, and provide therapy recommendations for
      ill recipients. DESIGN: Public health investigation. SETTING: Two transplant
      hospitals and community interview with the deceased donor's family. PATIENTS:
      Three transplant recipients and the organ donor. MEASUREMENTS: Specimens were
      tested for microsporidia by using culture, immunofluorescent antibody, polymerase
      chain reaction,immunohistochemistry, and electron microscopy. Donor medical
      records were reviewed and a questionnaire was developed to assess for
      microsporidial infection. RESULTS: Kidneys and lungs were procured from the
      deceased donor and transplanted to 3 recipients who became ill with fever 7 to 10
      weeks after the transplant. Results of urine culture, serologic,and polymerase
      chain reaction testing were positive for E. cuniculi of genotype III in each
      recipient; the organism was also identified in biopsy or autopsy specimens in all
      recipients. The donor had positive serologic test results for E. cuniculi.
      Surviving recipients received albendazole. Donor assessment did not identify
      factors for suspected E. cuniculi infection. LIMITATION: Inability to detect
      organism by culture or polymerase chain reaction in donor due to lack of autopsy
      specimens. CONCLUSION: Microsporidiosis is now recognized as an emerging
      transplant-associated disease and should be considered in febrile transplant
      recipients when tests for routinely encountered agents are unrevealing. Donor
      derived disease is critical to assess when multiple recipients from a common
      donor are ill.

PMID- 24727840
TI  - Cost-effectiveness of genotype-guided and dual antiplatelet therapies in acute
      coronary syndrome.
AB  - BACKGROUND: The choice of antiplatelet therapy after acute coronary syndrome
      (ACS) is complicated: Ticagrelor and prasugrel are novel alternatives to
      clopidogrel, patients with some genotypes may not respond to clopidogrel, and low
      cost generic formulations of clopidogrel are available. OBJECTIVE: To determine
      the most cost-effective strategy for dual antiplatelet therapy after percutaneous
      coronary intervention for ACS. DESIGN: Decision-analytic model. DATA SOURCES:
      Published literature, Medicare claims, and life tables. TARGET POPULATION:
      Patients having percutaneous coronary intervention for ACS. TIME HORIZON:
      Lifetime. PERSPECTIVE: Societal. INTERVENTION: Five strategies were examined:
      generic clopidogrel, prasugrel, ticagrelor, and genotyping for polymorphisms of
      CYP2C19 with carriers of loss-of-function alleles receiving either ticagrelor
      (genotyping with ticagrelor) or prasugrel (genotyping with prasugrel) and
      noncarriers receiving clopidogrel. OUTCOME MEASURES: Direct medical costs,
      quality-adjusted life years(QALYs), and incremental cost-effectiveness ratios
      (ICERs). RESULTS OF BASE-CASE ANALYSIS: The clopidogrel strategy produced$179 301
      in costs and 9.428 QALYs. Genotyping with prasugrel was superior to prasugrel
      alone, with an ICER of $35 800 per QALY relative to clopidogrel. Genotyping with
      ticagrelor was more effective than genotyping with prasugrel ($30 200 per QALY
      relative to clopidogrel). Ticagrelor was the most effective strategy($52 600 per
      QALY relative to genotyping with ticagrelor). RESULTS OF SENSITIVITY ANALYSIS:
      Stronger associations between genotype and thrombotic outcomes rendered
      ticagrelor substantially less cost-effective ($104 800 per QALY). Genotyping with
      prasugrel was the preferred therapy among patients who could not tolerate
      ticagrelor. LIMITATION: No randomized trials have directly compared genotyping
      strategies or prasugrel with ticagrelor. CONCLUSION: Genotype-guided
      personalization may improve the cost-effectiveness of prasugrel and ticagrelor
      after percutaneous coronary intervention for ACS, but ticagrelor for all patients
      may bean economically reasonable alternative in some settings.

PMID- 24727841
TI  - Treatment of primary Sjogren syndrome with rituximab: a randomized trial.
AB  - BACKGROUND: Primary Sjogren syndrome (pSS) is an autoimmune disorder
      characterized by ocular and oral dryness or systemic manifestations. OBJECTIVE:
      To evaluate efficacy and harms of rituximab in adults with recent-onset or
      systemic pSS. DESIGN: Randomized, placebo-controlled, parallel-group trial
      conducted between March 2008 and January 2011. Study personnel (except
      pharmacists), investigators, and patients were blinded to treatment group.
      (ClinicalTrials.gov: NCT00740948). SETTING: 14 university hospitals in France.
      PATIENTS: 120 patients with scores of 50 mm or greater on at least 2 of 4 visual
      analogue scales (VASs) (global disease, pain, fatigue, and dryness) and recent
      onset (< 10 years) biologically active or systemic pSS. INTERVENTION:
      Randomization (1:1 ratio) to rituximab (1 g at weeks 0 and 2) or placebo.
      MEASUREMENTS: Primary end point was improvement of at least 30 mm in 2 of 4 VASs
      by week 24. RESULTS: No significant difference between groups in the primary end
      point was found (difference, 1.0% [95% CI, -16.7% to 18.7%]). The proportion of
      patients with at least 30-mm decreases in at least two of the four VAS scores was
      higher in the rituximab group at week 6 (22.4% vs. 9.1%; P = 0.036). An
      improvement of at least 30 mm in VAS fatigue score was more common with rituximab
      at weeks 6 (P < 0.001) and 16 (P = 0.012), and improvement in fatigue from
      baseline to week 24 was greater with rituximab. Adverse events were similar
      between groups except for a higher rate of infusion reactions with rituximab.
      LIMITATION: Low disease activity at baseline and a primary outcome that may have
      been insensitive to detect clinically important changes. CONCLUSION: Rituximab
      did not alleviate symptoms or disease activity in patients with pSS at week 24,
      although it alleviated some symptoms at earlier time points.

PMID- 24727843
TI  - Random-effects meta-analysis of inconsistent effects: a time for change.
AB  - A primary goal of meta-analysis is to improve the estimation of treatment effects
      by pooling results of similar studies. This article explains how the most widely
      used method for pooling heterogeneous studies--the Der Simonian-Laird (DL)
      estimator--can produce biased estimates with falsely high precision. A classic
      example is presented to show that use of the DL estimator can lead to erroneous
      conclusions. Particular problems with the DL estimator are discussed, and several
      alternative methods for summarizing heterogeneous evidence are presented. The
      authors support replacing universal use of the DL estimator with analyses based
      on a critical synthesis that recognizes the uncertainty in the evidence,focuses
      on describing and explaining the probable sources of variation in the evidence,
      and uses random-effects estimates that provide more accurate confidence limits
      than the DL estimator.

PMID- 24727842
TI  - Functional status and quality of life after transcatheter aortic valve
      replacement: a systematic review.
AB  - BACKGROUND: The functional and quality-of-life benefits of transcatheter aortic
      valve replacement (TAVR) have not been established. PURPOSE: To evaluate the
      changes in functional status and quality of life after TAVR. DATA SOURCES:
      MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials from 1
      January 2002 to 30 September 2013. STUDY SELECTION: Studies of TAVR that reported
      the New York Heart Association (NYHA) class, Short Form-12/36 Health Survey
      physical and mental component summary (points), or other measures of functional
      status. DATA EXTRACTION: Two reviewers independently extracted the mean change
      (follow-up minus baseline) in primary outcomes. Because of substantial
      heterogeneity, data were not pooled; the range of mean change was summarized.
      DATA SYNTHESIS: We identified 60 observational studies (56 pre-post comparison
      and 4 head-to-head comparative studies) and 2 randomized, controlled trials (11
      205 patients). Most studies showed a clinically important decrease in NYHA class
      at 6 to 11 months (range, -0.8 to -2.1 classes) and 12 to 23 months (range, -0.8
      to -2.1 classes). The improvement in the Short Form-12/36 Health Survey physical
      component score was clinically important over 12 months (range, 4.9 to 26.9
      points), and the change in mental component score was smaller (range, 1.0 to 8.9
      points).Clinically important improvements were seen in other disease-specific
      measures but were less consistently seen in general health measures. LIMITATIONS:
      Comparative evidence is limited by few head-to-head studies. Survivor bias may
      have overestimated the benefits. CONCLUSION: Transcatheter aortic valve
      replacement provides clinically important benefits in physical function and
      disease-specific measures of quality of life but modest benefits in psychological
      and general health measures. More comparative studies on functional status and
      quality of life are needed for informed treatment decision making.

PMID- 24727844
TI  - Life-saving organ transplants accompanied by stealthy and unexpected pathogens.

PMID- 24727845
TI  - Evidence-based medicine, pharmacogenetics, and antiplatelet therapy decision
      making for acute coronary syndrome.

PMID- 24727847
TI  - Low-level laser liposuction and hypertriglyceridemia.

PMID- 24727846
TI  - On being a doctor again.

PMID- 24727849
TI  - The sign.

PMID- 24727848
TI  - Pituitary adenoma as an incidental finding in dental radiology: a case report.

PMID- 24727851
TI  - Correction: rilonacept for colchicine-resistant or -intolerant familial
      mediterranean Fever.

PMID- 24727850
TI  - Correction: taking the bite out of rabies, putting teeth into "one health".

PMID- 24727852
TI  - No matter.

PMID- 24727853
TI  - Using unplanned fires to help suppressing future large fires in Mediterranean
      forests.
AB  - Despite the huge resources invested in fire suppression, the impact of wildfires
      has considerably increased across the Mediterranean region since the second half
      of the 20th century. Modulating fire suppression efforts in mild weather
      conditions is an appealing but hotly-debated strategy to use unplanned fires and
      associated fuel reduction to create opportunities for suppression of large fires
      in future adverse weather conditions. Using a spatially-explicit fire-succession
      model developed for Catalonia (Spain), we assessed this opportunistic policy by
      using two fire suppression strategies that reproduce how firefighters in extreme
      weather conditions exploit previous fire scars as firefighting opportunities. We
      designed scenarios by combining different levels of fire suppression efficiency
      and climatic severity for a 50-year period (2000-2050). An opportunistic fire
      suppression policy induced large-scale changes in fire regimes and decreased the
      area burnt under extreme climate conditions, but only accounted for up to 18-22%
      of the area to be burnt in reference scenarios. The area suppressed in adverse
      years tended to increase in scenarios with increasing amounts of area burnt
      during years dominated by mild weather. Climate change had counterintuitive
      effects on opportunistic fire suppression strategies. Climate warming increased
      the incidence of large fires under uncontrolled conditions but also indirectly
      increased opportunities for enhanced fire suppression. Therefore, to shift fire
      suppression opportunities from adverse to mild years, we would require a
      disproportionately large amount of area burnt in mild years. We conclude that the
      strategic planning of fire suppression resources has the potential to become an
      important cost-effective fuel-reduction strategy at large spatial scale. We do
      however suggest that this strategy should probably be accompanied by other fuel
      reduction treatments applied at broad scales if large-scale changes in fire
      regimes are to be achieved, especially in the wider context of climate change. 

PMID- 24727854
TI  - Clinical utility of 18F-FDG positron emission tomography in malignant peritoneal
      mesothelioma.
AB  - BACKGROUND: The purpose of this study was to determine the utility of 18F-FDG-PET
      for evaluating the presence and the extent of malignant peritoneal mesothelioma
      (MPM), for disease surveillance/recurrence detection and for evaluating response
      to therapy. METHODS: We retrospectively analyzed clinical and imaging data of 60
      MPM patients (34 women and 26 men, mean age 53.6 y, range 18-80 y) who had
      multiple 18F-FDG-PET/CT or PET scans (18F-FDG scans) at various stages of the
      disease. RESULTS: Eleven patients had baseline pretreatment scans and all 11
      scans showed 18F-FDG avid diffuse, nodular or mixed disease distribution patterns
      characteristic of MPM. Four patients out of eleven had an early post-treatment
      18F-FDG scan (<6 months) and all scans were accurate in determining response to
      treatment. Forty-nine patients with a history of treated MPM without baseline
      scans had multiple disease surveillance 18F-FDG scans. Their initial 18F-FDG
      scans had an accuracy of 82% and positive predictive value of 83% and negative
      predictive value of 80% for the detection of disease presence and disease-free
      state, respectively. For fifteen patients with a true negative 18F-FDG scan, a
      second follow-up scan accurately detected disease recurrence or absence of
      recurrence in all cases. Metastatic or remote nodal disease was more common in
      the biphasic histopathologic subtype group while pleural disease was
      predominantly seen in the epithelial MPM group. No relationship was found between
      the uptake pattern and the histopathologic subtype. CONCLUSION: 18F-FDG-PET is a
      valuable imaging modality in the pre-surgical evaluation and management of MPM
      and further prospective studies are warranted.

PMID- 24727855
TI  - A gram-scale route to phlegmarine alkaloids: rapid total synthesis of (-)
      cermizine B.
AB  - The synthesis of the Lycopodium alkaloid (-)-cermizine B (1), which establishes
      its absolute configuration, is achieved by combining asymmetric organocatalysis
      and an uninterrupted eight-step reaction sequence, followed by a final reduction
      step. This "pot-economy" strategy provides access to the cis-phlegmarine
      stereoparent embedded in 1 for the first time, rapidly and on a gram-scale.

PMID- 24727856
TI  - The water-soluble triptolide derivative PG490-88 protects against cisplatin
      induced acute kidney injury.
AB  - Triptolide, a traditional Chinese medicine, has anti-inflammatory,
      antiproliferative, and proapoptotic properties. As interstitial inflammation and
      tubular apoptosis are features of cisplatin-induced acute kidney injury (AKI), we
      determined the effect of the water-soluble triptolide derivative 14-succinyl
      triptolide sodium salt (PG490-88) in a mouse model of cisplatin-induced AKI.
      PG490-88 resulted in a significant decrease in blood urea nitrogen (BUN), serum
      creatinine, and acute tubular necrosis (ATN) score, and a nonsignificant increase
      in tubular apoptosis score in AKI. The mitogen-activated protein kinase (MAPK)
      pathway is activated in AKI. On immunoblot analysis, phosphoextracellular signal
      regulated kinase (p-ERK) was increased 3.6-fold in AKI and 2.0-fold inhibited by
      PG490-88. Phospho-c-Jun N-terminal kinase (p-JNK) was increased in AKI. PG490-88
      resulted in a nonsignificant decrease in p-JNK. Phospho-p38 was not affected by
      cisplatin or PG490-88. MAPK phosphatase-1 (MKP-1) that negatively regulates MAPK
      signaling has not previously been studied in AKI. MKP-1 activity was not affected
      by cisplatin or PG490-88. Changes in p-ERK, p-JNK, and MKP-1 were confirmed on
      reverse protein phase analysis. The ERK inhibitor U0126 resulted in lower BUN and
      serum creatinine, suggesting a mechanistic role of ERK in AKI. The increase in
      interleukin-1alpha (IL-1alpha), IL-1beta, IL-6, CXCL1, and IL-33 in the kidney in
      AKI was unaffected by PG490-88. In summary, PG490-88 protects against AKI and ATN
      despite no decrease in tubular apoptosis. The protection of PG490-88 against AKI
      was associated with a decrease in p-ERK and was independent of MKP-1 and
      proinflammatory cytokines. In conclusion, PG490-88 protects against cisplatin
      induced AKI possibly by decreasing p-ERK. 

PMID- 24727857
TI  - Orientation-tuning in self-assembled heterostructures induced by a buffer layer.
AB  - Anisotropic nano-plate structures in self-assembled perovskite-spinel thin films,
      BiFeO3-NiFe2O4 and BiFeO3-CoFe2O4, which were deposited on (001)c SrRuO3/SrTiO3
      and DyScO3 substrates, respectively, have been demonstrated using transmission
      electron microscopy combined with strain analysis. Unlike the unitary cube-on
      cube orientation relationship reported widely, the growth direction of the
      CoFe2O4 and NiFe2O4 plates was tuned to [011]c while the BiFeO3 matrix kept
      [001]c in both systems. In particular, a thin stress-sensitive BiFeO3 buffer
      layer between the spinel nanostructure and the substrate was introduced for
      providing a complex strain state in both film systems. The novel orientation
      tuning and the pattern configuration of the heterostructures are mainly
      attributed to the strain imposed on the films and the anisotropic ledge growth
      mechanism of spinels. 

PMID- 24727858
TI  - Bisphenol AF-induced endogenous transcription is mediated by ERalpha and ERK1/2
      activation in human breast cancer cells.
AB  - Bisphenol AF (BPAF)-induced transcriptional activity has been evaluated by
      luciferase reporter assay. However, the molecular mechanism of BPAF-induced
      endogenous transcription in human breast cancer cells has not been fully
      elucidated. In the present study, we investigated the effect and mechanism of
      BPAF-induced endogenous transcription detected by real-time PCR in human breast
      cancer cells. We found that BPAF stimulated transcription of estrogen responsive
      genes, such as trefoil factor 1 (TFF1), growth regulation by estrogen in breast
      cancer 1 (GREB1) and cathepsin D (CTSD), through dose-dependent and time
      dependent manners in T47D and MCF7 cells. Gene-silencing of ERalpha, ERbeta and G
      protein-coupled estrogen receptor 1 (GPER) by small interfering RNA revealed that
      BPAF-induced endogenous transcription was dependent on ERalpha and GPER, implying
      both genomic and nongenomic pathways might be involved in the endogenous
      transcription induced by BPAF. ERalpha-mediated gene transcription was further
      confirmed by inhibition of ER activity using ICI 182780 in ERalpha-positive T47D
      and MCF7 cells as well as overexpression of ERalpha in ERalpha-negative MDA-MB
      231 breast cancer cells. Moreover, we utilized Src tyrosine kinase inhibitor PP2
      and two MEK inhibitors PD98059 and U0126 to elucidate the rapid nongenomic
      activation of Src/MEK/ERK1/2 cascade on endogenous transcription. Our data showed
      that BPAF-induced transcription could be significantly blocked by PP2, PD98059
      and U0126, suggesting activation of ERK1/2 was also required to regulate
      endogenous transcription. Taken together, these results indicate that BPAF
      induced endogenous transcription of estrogen responsive genes is mediated through
      both genomic and nongenomic pathways involving the ERalpha and ERK1/2 activation
      in human breast cancer cells. 

PMID- 24727859
TI  - A time resolved metabolomics study: the influence of different carbon sources
      during growth and starvation of Bacillus subtilis.
AB  - In its natural environment, the soil, the Gram-positive model bacterium Bacillus
      subtilis frequently encounters nutrient limitation and other stress factors.
      Efficient adaptation mechanisms are necessary to cope with this wide range of
      environmental challenges. The ability to utilize diverse carbon sources
      represents a key adaptation process that allows B. subtilis to thrive in its
      natural habitat. To gain a comprehensive insight into the metabolism of B.
      subtilis, global metabolite analyses were performed during growth with glucose
      alone or glucose with either malate, fumarate or citrate as carbon/energy
      sources. Furthermore, to achieve a comprehensive coverage of a wide range of
      chemically different metabolites, complementary GC-MS, LC-MS and (1)H-NMR
      analyses were applied. This study reveals that the availability of different
      carbon sources results in different extracellular metabolite profiles whereas a
      regulated intracellular metabolite equilibrium was observed. In addition, the
      typical energy-starvation induced activation of the general stress sigma factor
      sigma(B) was only observed upon entry into the stationary phase with glucose or
      glucose and malate as carbon sources.

PMID- 24727860
TI  - The reaction mechanism of FeSb(2) as anode for sodium-ion batteries.
AB  - The electrochemical reaction of FeSb2 with Na is reported for the first time. The
      first discharge (sodiation) potential profile of FeSb2 is characterized by a
      gentle slope centered at 0.25 V. During charge (Na removal) and the subsequent
      discharge, the main reaction takes place near 0.7 V and 0.4 V, respectively. The
      reversible storage capacity amounts to 360 mA h g(-1), which is smaller than the
      theoretical value of 537 mA h g(-1). The reaction, studied by ex situ and in situ
      X-ray diffraction, is found to proceed by the consumption of crystalline FeSb2 to
      form an amorphous phase. Upon further sodiation, the formation of nanocrystalline
      Na3Sb domains is evidenced. During desodiation, Na3Sb domains convert into an
      amorphous phase. The chemical environment of Fe, probed by (57)Fe Mossbauer
      spectroscopy, undergoes significant changes during the reaction. During
      sodiation, the well-resolved doublet of FeSb2 with an isomer shift around 0.45 mm
      s(-1) and a quadrupole splitting of 1.26 mm s(-1) is gradually converted into a
      doublet line centered at about 0.15 mm s(-1) along with a singlet line around 0
      mm s(-1). The former signal results from the formation of a Fe-rich FexSb alloy
      with an estimated composition of 'Fe4Sb' while the latter signal corresponds to
      superparamagnetic Fe due to the formation of nanosized pure Fe domains.
      Interestingly the signal of 'Fe4Sb' remains unaltered during desodiation. This
      mechanism is substantially different than that observed during the reaction with
      Li. The irreversible formation of a Fe-rich 'Fe4Sb' alloy and the absence of full
      desodiation of Sb domains explain the lower than theoretical practical storage
      capacity. 

PMID- 24727862
TI  - A robust post-processing workflow for datasets with motion artifacts in diffusion
      kurtosis imaging.
AB  - PURPOSE: The aim of this study was to develop a robust post-processing workflow
      for motion-corrupted datasets in diffusion kurtosis imaging (DKI). MATERIALS AND
      METHODS: The proposed workflow consisted of brain extraction, rigid registration,
      distortion correction, artifacts rejection, spatial smoothing and tensor
      estimation. Rigid registration was utilized to correct misalignments. Motion
      artifacts were rejected by using local Pearson correlation coefficient (LPCC).
      The performance of LPCC in characterizing relative differences between artifacts
      and artifact-free images was compared with that of the conventional correlation
      coefficient in 10 randomly selected DKI datasets. The influence of rejected
      artifacts with information of gradient directions and b values for the parameter
      estimation was investigated by using mean square error (MSE). The variance of
      noise was used as the criterion for MSEs. The clinical practicality of the
      proposed workflow was evaluated by the image quality and measurements in regions
      of interest on 36 DKI datasets, including 18 artifact-free (18 pediatric
      subjects) and 18 motion-corrupted datasets (15 pediatric subjects and 3 essential
      tremor patients). RESULTS: The relative difference between artifacts and artifact
      free images calculated by LPCC was larger than that of the conventional
      correlation coefficient (p<0.05). It indicated that LPCC was more sensitive in
      detecting motion artifacts. MSEs of all derived parameters from the reserved data
      after the artifacts rejection were smaller than the variance of the noise. It
      suggested that influence of rejected artifacts was less than influence of noise
      on the precision of derived parameters. The proposed workflow improved the image
      quality and reduced the measurement biases significantly on motion-corrupted
      datasets (p<0.05). CONCLUSION: The proposed post-processing workflow was reliable
      to improve the image quality and the measurement precision of the derived
      parameters on motion-corrupted DKI datasets. The workflow provided an effective
      post-processing method for clinical applications of DKI in subjects with
      involuntary movements.

PMID- 24727861
TI  - Similar replicative fitness is shared by the subtype B and unique BF recombinant
      HIV-1 isolates that dominate the epidemic in Argentina.
AB  - The HIV-1 epidemic in South America is dominated by pure subtypes (mostly B and
      C) and more than 7 BF and BC recombinant forms. In Argentina, circulating
      recombinant forms (CRFs) comprised of subtypes B and F make up more than 50% of
      HIV infections. For this study, 28 HIV-1 primary isolates were obtained from
      patients in Buenos Aires, Argentina and initially classified into subtype B (n =
      9, 32.1%), C (n = 1, 3.6%), and CRFs (n = 18, 64.3%) using partial pol and vpu
      env sequences, which proved to be inconsistent and inaccurate for these
      phylogenetic analyses. Near full length genome sequences of these primary HIV-1
      isolates revealed that nearly all intersubtype BF recombination sites were unique
      and countered previous "CRF" B/F classifications. The majority of these
      Argentinean HIV-1 isolates were CCR5-using but 4 had a dual/mixed tropism as
      predicted by both phenotypic and genotypic assays. Comparison of the replicative
      fitness of these BF primary HIV-1 isolates to circulating B, F, and C HIV-1 using
      pairwise competitions in peripheral blood mononuclear cells (PBMCs) indicated a
      similarity in fitness of these BF recombinants to subtypes B and F HIV-1 (of the
      same co-receptor usage) whereas subtype C HIV-1 was significantly less fit than
      all as previously reported. These results suggest that the multitude of BF HIV-1
      strains present within the Argentinean population do not appear to have gained
      replicative fitness following recent B and F recombination events. 

PMID- 24727863
TI  - Microwave assisted synthesis of pyrido[2,3-a]carbazoles; investigation of in
      vitro DNA binding/cleavage, antioxidant and cytotoxicity studies.
AB  - We have developed an effective microwave assisted p-TsOH catalyzed synthesis of
      pyrido[2,3-a]carbazoles via a one pot reaction of ethanolamine and 1-chloro-2
      formyl carbazoles. The structure has been characterized by spectroscopic methods.
      The electronic spectroscopic experimental evidence strongly showed that the
      compounds could interact with calf thymus DNA (CT-DNA) through intercalation with
      a binding constant value of 1.2-3.0*10(4)M(-)(1). All the compounds showed weak
      to moderate capacity of scavenging with DPPH. The cytotoxicity has been evaluated
      by MTT assay against MCF-7 cell line and compared with standard drug cisplatin. 

PMID- 24727864
TI  - Effect of APCD and APCF subunits depletion on phycobilisome fluorescence of the
      cyanobacterium Synechocystis PCC 6803.
AB  - Long-wavelength allophycocyanin (APC) subunits in cyanobacteria (APCD, APCE, and
      APCF) are required for phycobilisome (PBS) assembly, stability, and energy
      transfer to photosystems. Here we studied fluorescence properties of PBS in vivo,
      using Synechocystis PCC 6803 mutant cells deficient in both photosystems and/or
      long-wavelength APC subunits. At room temperature, an absence of APCD and APCF
      subunits resulted in ~2-fold decrease of long-wavelength APC (APC680)
      fluorescence. In 77K fluorescence spectra, we observed only a slight shift of
      long-wavelength emission. However, 77K fluorescence of a PSI/PSII/APCF-less
      mutant was also characterized by increased emission from short-wavelength APC,
      which suggested the importance of this subunit in energy transfer from APC660 to
      APC680. Under blue-green actinic light, all mutants showed significant non
      photochemical fluorescence quenching of up to 80% of the initial dark
      fluorescence level. Based on the mutants' quenching spectra, we determined
      quenching to originate from the pool of short-wavelength APC, while the spectral
      data alone was not sufficient to make unambiguous conclusion on the involvement
      of long-wavelength APC in non-photochemical quenching. Using a model of quenching
      center formation, we determined interaction rates between PBS and orange
      carotenoid protein (OCP) in vivo. Absence of APCD or APCF subunits had no effect
      on the rates of quenching center formation confirming the data obtained for
      isolated OCP-PBS complexes. Thus, although APCD and APCF subunits were required
      for energy transfer in PBS in vivo, their absence did not affect rates of OCP-PBS
      binding. 

PMID- 24727865
TI  - Comparison of validity of mapping between drug indications and ICD-10. Direct and
      indirect terminology based approaches.
AB  - BACKGROUND: Mapping of drug indications to ICD-10 was undertaken in Korea by a
      public and a private institution for their own purposes. A different mapping
      approach was used by each institution, which presented a good opportunity to
      compare the validity of the two approaches. OBJECTIVES: This study was undertaken
      to compare the validity of a direct mapping approach and an indirect terminology
      based mapping approach of drug indications against the gold standard drawn from
      the results of the two mapping processes. METHODS: Three hundred and seventy-five
      cardiovascular reference drugs were selected from all listed cardiovascular drugs
      for the study. In the direct approach, two experienced nurse coders mapped the
      free text indications directly to ICD-10. In the indirect terminology based
      approach, the indications were extracted and coded in the Korean Standard
      Terminology of Medicine. These terminology coded indications were then manually
      mapped to ICD-10. The results of the two approaches were compared to the gold
      standard. A kappa statistic was calculated to see the compatibility of both
      mapping approaches. Recall, precision and F1 score of each mapping approach were
      calculated and analyzed using a paired t-test. RESULTS: The mean number of
      indications for the study drugs was 5.42. The mean number of ICD-10 codes that
      matched in direct approach was 46.32 and that of indirect terminology based
      approach was 56.94. The agreement of the mapping results between the two
      approaches were poor (kappa = 0.19). The indirect terminology based approach
      showed higher recall (86.78%) than direct approach (p < 0.001). However, there
      was no difference in precision and F1 score between the two approaches.
      CONCLUSIONS: Considering no differences in the F1 scores, both approaches may be
      used in practice for mapping drug indications to ICD-10. However, in terms of
      consistency, time and manpower, better results are expected from the indirect
      terminology based approach.

PMID- 24727866
TI  - An attractor-based complexity measurement for Boolean recurrent neural networks.
AB  - We provide a novel refined attractor-based complexity measurement for Boolean
      recurrent neural networks that represents an assessment of their computational
      power in terms of the significance of their attractor dynamics. This complexity
      measurement is achieved by first proving a computational equivalence between
      Boolean recurrent neural networks and some specific class of omega-automata, and
      then translating the most refined classification of omega-automata to the Boolean
      neural network context. As a result, a hierarchical classification of Boolean
      neural networks based on their attractive dynamics is obtained, thus providing a
      novel refined attractor-based complexity measurement for Boolean recurrent neural
      networks. These results provide new theoretical insights to the computational and
      dynamical capabilities of neural networks according to their attractive
      potentialities. An application of our findings is illustrated by the analysis of
      the dynamics of a simplified model of the basal ganglia-thalamocortical network
      simulated by a Boolean recurrent neural network. This example shows the
      significance of measuring network complexity, and how our results bear new
      founding elements for the understanding of the complexity of real brain circuits.

PMID- 24727867
TI  - Impact of hyperaemic microvascular resistance on fractional flow reserve
      measurements in patients with stable coronary artery disease: insights from
      combined stenosis and microvascular resistance assessment.
AB  - BACKGROUND: Fractional flow reserve (FFR) aims to identify the extent of
      epicardial disease, but may be obscured by involvement of the coronary
      microvasculature. We documented the impact of hyperaemic stenosis resistance
      (HSR) and hyperaemic microvascular resistance (HMR) on FFR, and its relationship
      with myocardial ischaemia in patients with stable coronary artery disease.
      METHODS AND RESULTS: We evaluated 255 coronary arteries with stenoses of
      intermediate severity by means of intracoronary pressure and flow measurements to
      determine FFR, HSR and HMR. Myocardial perfusion scintigraphy (MPS) was performed
      to identify inducible myocardial ischaemia. In 178 patients, HMR was additionally
      determined in a reference coronary artery. Target vessel HMR was stratified
      according to reference vessel HMR tertiles. The diagnostic OR for inducible
      ischaemia on MPS of a positive compared with a negative FFR was significantly
      higher only in the presence of a high HMR (at the 0.75 and 0.80 FFR cut-off).
      Among stenoses with a positive FFR, the prevalence of ischaemia was significantly
      higher when HMR was high despite equivalent FFR across the HMR groups. This was
      paralleled by a concomitant significant increase in HSR with increasing HMR
      across groups. The relation between FFR and HSR (r(2)=0.54, p<0.001) was
      modulated by the magnitude of HMR, and improved substantially after adjustment
      for HMR (adjusted-r(2)=0.73, p<0.001), where, for epicardial disease of
      equivalent severity, FFR increased with increasing HMR. CONCLUSIONS:
      Identification of epicardial disease severity by FFR is partly obscured by the
      microvascular resistance, which illustrates the necessity of combined pressure
      and flow measurements in daily practice.

PMID- 24727868
TI  - Does it Matter if we get it right? Impact of appropriateness of empiric
      antimicrobial therapy among surgical patients.
AB  - Previous studies have shown conflicting evidence regarding the impact of
      inappropriate, initial antibiotic therapy. The purpose of this study was to
      evaluate the impact of inappropriate empiric antimicrobial therapy for the
      treatment of infection among surgical patients. We hypothesized that
      inappropriate empiric antimicrobial therapy would predict increased mortality
      risk compared with appropriate therapy. This was a retrospective analysis of a
      prospectively maintained database of all surgical patients admitted to a tertiary
      care center from 1996 to 2007 and treated for sepsis. "Appropriate" empiric
      antibiotic treatment was determined by sensitivity testing. Demographics and
      comorbidities, infection sites, infection organisms, and outcomes were compared
      between inappropriately and appropriately treated groups. Multivariable log
      binomial regression was performed. There were 2,855 patients (7,158 infectious
      episodes) identified by culture analysis as either appropriately or
      inappropriately treated. Three hundred seventeen (15%) inappropriately treated
      infectious episodes resulted in death compared with 718 (14%) of the
      appropriately treated infectious episodes. After adjusting for statistically
      significant variables, inappropriately treated episodes of infection were not
      found to be associated with an increased risk for mortality compared with
      appropriately treated episodes of infection (relative risk, 1.0; 95% confidence
      interval, 0.99 - 1.02; P = 0.36). Our study observed no difference in mortality
      between appropriately and inappropriately treated infections within a surgical
      population. 

PMID- 24727869
TI  - Direct molecular detection of pathogens in blood as specific rule-in diagnostic
      biomarker in patients with presumed sepsis: our experience on a heterogeneous
      cohort of patients with signs of infective systemic inflammatory response
      syndrome.
AB  - The practical value of blood cultures in the diagnosis of sepsis is impaired by a
      delay in the turnaround time to result and by the fact that blood culture
      positive can be found for only about 30% of these patients. Conventional
      laboratory signs of sepsis and acute phase protein biomarkers are sensitive and
      easy to use, but often also very nonspecific. Molecular diagnostic reflects
      currently the most promising avenue to decrease time to result and to influence
      decision making for antibiotic therapy in the septic host. In this study, we wish
      to highlight the impact of the LightCycler SeptiFast, a multipathogen probe-based
      real-time polymerase chain reaction, in the rapid etiological diagnosis of sepsis
      in patients with clinical and laboratory signs of bloodstream infections. We have
      evaluated prospectively 830 adult patients with suspected bloodstream infection
      and at least two criteria of systemic inflammatory response syndrome. In more
      than 50% of critically ill patients strongly suspected of having sepsis, we
      arrived to an etiological diagnosis only by the molecular method in a median time
      of 15 h, with specificity and predictive positive values of 96% and 94%,
      respectively. We highlight the role of DNAemia as time-critical, high
      specificity, etiological, non-culture-based rule-in diagnostic biomarker in
      patients with presumed sepsis. 

PMID- 24727870
TI  - Plasma angiopoietin 2 concentrations are related to impaired lung function and
      organ failure in a clinical cohort receiving high-dose interleukin 2 therapy.
AB  - INTRODUCTION: The pathophysiology and therapeutic options in sepsis-induced lung
      injury remain elusive. High-dose interleukin 2 therapy (HDIL-2) is an important
      protocol for advanced malignancies but is limited by systemic inflammation and
      pulmonary edema that is indistinguishable from sepsis. In preclinical models, IL
      2 stimulates angiopoietin 2 (AngP-2) secretion, which increases endothelial
      permeability and causes pulmonary edema. However, these relationships have not
      been fully elucidated in humans. Furthermore, the relevance of plasma AngP-2 to
      organ function is not clear. We hypothesized that plasma AngP-2 concentrations
      increase during HDIL-2 and are relevant to clinical pathophysiology. METHODS: We
      enrolled 13 subjects with metastatic melanoma or renal cell carcinoma admitted to
      receive HDIL-2 and collected blood and spirometry data daily. The plasma
      concentrations of AngP-2 and IL-6 were measured with enzyme-linked immunosorbent
      assay. RESULTS: At baseline, the mean AngP-2 concentration was 2.5 (SD, 1.0)
      ng/mL. Angiopoietin 2 concentrations increased during treatment: the mean
      concentration on the penultimate day was 16.0 (SD, 4.5) ng/mL and increased
      further to 18.6 (SD, 4.9) ng/mL (P < 0.05 vs. penultimate) during the last day of
      therapy. The forced expiratory volume in 1 s decreased during treatment.
      Interestingly, plasma AngP-2 concentrations correlated negatively with forced
      expiratory volume in 1 s (Spearman r = -0.78, P < 0.0001). Plasma AngP-2
      concentrations also correlated with plasma IL-6 concentrations (r = 0.61, P <
      0.0001) and Sequential Organ Failure Assessment scores (r = 0.68, P < 0.0001).
      CONCLUSIONS: Plasma AngP-2 concentrations increase during HDIL-2 administration
      and correlate with pulmonary dysfunction. High-dose IL-2 may serve as a clinical
      model of sepsis and acute lung injury. Further investigation is warranted.

PMID- 24727871
TI  - Off-pump CABG surgery reduces systemic inflammation compared with on-pump surgery
      but does not change systemic endothelial responses: a prospective randomized
      study.
AB  - Coronary artery bypass graft (CABG) surgery can result in severe postoperative
      organ failure. During CABG surgery, cardiopulmonary bypass (CPB) with cardiac
      arrest is often used (on-pump CABG), which often results in a systemic
      inflammatory response. To reduce this inflammatory response, off-pump CABG was
      reintroduced, thereby avoiding CPB. There is increasing evidence that the
      endothelium plays an important role in the pathophysiology of organ failure after
      CABG surgery. In this study, 60 patients who were scheduled for elective CABG
      surgery were randomized to have surgery for on-pump or off-pump CABG. Blood was
      collected at four time points: start, end, 6 h, and 24 h postoperatively. Levels
      of inflammatory cytokines, soluble adhesion molecules, and angiogenic factors and
      their receptors were measured in the plasma. No differences were found in
      preoperative characteristics between the patient groups. The levels of tumor
      necrosis factor-alpha, interleukin 10, and myeloperoxidase, but not interleukin
      6, were increased to a greater extent in the on-pump CABG compared with off-pump
      CABG after sternum closure. The soluble endothelial adhesion molecules E
      selectin, vascular cell adhesion molecule 1, and intracellular adhesion molecule
      1 were not elevated in the plasma during and after CABG surgery in both on-pump
      and off-pump CABG. Angiopoietin 2 was only increased 24 h after surgery in both
      on-pump and off-pump CABG. Higher levels of sFlt-1 were found after sternum
      closure in off-pump CABG compared with on-pump CABG. Avoiding CPB and aortic
      cross clamping in CABG surgery reduces the systemic inflammatory response. On
      pump CABG does not lead to an increased release of soluble endothelial adhesion
      molecules in the circulation compared with off-pump CABG. 

PMID- 24727872
TI  - Utility of vital signs, heart rate variability and complexity, and machine
      learning for identifying the need for lifesaving interventions in trauma
      patients.
AB  - To date, no studies have attempted to utilize data from a combination of vital
      signs, heart rate variability and complexity (HRV, HRC), as well as machine
      learning (ML), for identifying the need for lifesaving interventions (LSIs) in
      trauma patients. The objectives of this study were to examine the utility of the
      above for identifying LSI needs and compare different LSI-associated models, with
      the hypothesis that an ML model would be superior in performance over
      multivariate logistic regression models. One hundred four patients transported
      from the injury scene via helicopter were selected for the study. A wireless
      vital signs monitor was attached to the patient's arm and used to capture
      physiologic data, including HRV and HRC. The power of vital sign measurements,
      HRV, HRC, and Glasgow Coma Scale score (GCS) to identify patients requiring LSIs
      was estimated using multivariate logistic regression and ML. Receiver operating
      characteristic (ROC) curves were also obtained. Thirty-two patients underwent 75
      LSIs. After logistic regression, ROC curves demonstrated better identification
      for LSIs using heart rate (HR) and HRC (area under the curve [AUC] of 0.81) than
      using HR alone (AUC of 0.73). Likewise, ROC curves demonstrated better
      identification for LSIs using GCS and HRC (AUC of 0.94) than using GCS and HR
      (AUC of 0.92). Importantly, ROC curves demonstrated that an ML model using HR,
      GCS, and HRC (AUC of 0.99) had superior performance over multivariate logistic
      regression models for identifying the need for LSIs in trauma patients.
      Development of computer decision support systems should utilize vital signs, HRC,
      and ML in order to achieve more accurate diagnostic capabilities, such as
      identification of needs for LSIs in trauma patients. 

PMID- 24727873
TI  - Cholesterol rather than procalcitonin or C-reactive protein predicts mortality in
      patients with infection.
AB  - Serum cholesterol procalcitonin (PCT) and C-reactive protein (CRP) levels were
      measured consecutively in 76 critically ill patients at admission to the
      intensive care unit. The presence of infection was defined according to the CDC
      (Centers for Disease Control and Prevention) criteria; in-house mortality,
      underlying diseases, and severity of sepsis were monitored. Nonsurvivors had
      significantly lower cholesterol levels compared with survivors (69 mg/dL [range,
      37-88 mg/dL] vs. 96 mg/dL [range, 71-132 mg/dL], P = 0.006) whereas no
      significant differences were noted for serum PCT and CRP levels. In a cohort of
      patients with cholesterol levels of 50 mg/dL or less, 82% did not survive as
      compared with patients with cholesterol levels of 100 mg/dL or greater
      (mortality, 21%). In a control group without infection, no difference of
      cholesterol, PCT, or CRP was found between survivors and nonsurvivors. Our data
      show that low cholesterol levels in patients with infectious disease have a
      prognostic value and may be useful markers to identify high-risk patients already
      at admission. 

PMID- 24727874
TI  - Preoperative biliary drainage for pancreatic cancer.
AB  - This review is to summarize the current knowledge about preoperative biliary
      drainage (PBD) in patients with biliary obstruction caused by pancreatic cancer.
      Most patients with pancreatic carcinoma (85%) will present with obstructive
      jaundice. The presence of toxic substances as bilirubin and bile salts, impaired
      liver function and altered nutritional status due to obstructive jaundice have
      been characterized as factors for development of complications after surgery.
      Whereas PBD was to yield beneficial effects in the experimental setting,
      conflicting results have been observed in clinical studies. The meta-analysis
      from relative older studies as well as more importantly a recent clinical trial
      showed that PBD should not be performed routinely. PBD for patients with a distal
      biliary obstruction is leading to more serious complications compared with early
      surgery. Arguments for PBD have shifted from a potential therapeutic benefit
      towards a logistic problem such as patients suffering from cholangitis and severe
      jaundice at admission or patients who need extra diagnostic tests, or delay in
      surgery due to a referral pattern or waiting list for surgery as well as
      candidates for neoadjuvant chemo(radio)therapy. If drainage is indicated in these
      patients it should be performed with a metal stent to reduce complications after
      the drainage procedure such as stent occlusion and cholangitis. Considering a
      change towards more neoadjuvant therapy regimes improvement of the quality of the
      biliary drainage concept is still important. 

PMID- 24727875
TI  - Current concept, diagnosis and pathogenesis of autoimmune pancreatitis as IgG4
      related disease.
AB  - Recently, autoimmune pancreatitis, a pancreatic manifestation of IgG4-related
      disease (IgG4-RD) has been recognized as a novel clinical entity associated with
      massive infiltration of IgG4-positive cells. The first international symposium on
      IgG4-RD endorsed the comprehensive nomenclature as IgG4-RD, which the Japanese
      research committee supported by the Ministry of Health, Labor and Welfare of
      Japan proposed in 2009, and proposed the individual nomenclatures for each organ
      system manifestations and the international pathologic consensus in 2011. In
      addition to the pathological consensus, the Japanese comprehensive diagnostic
      criteria (CDC) for IgG4-RD for general use, and several organ specific criteria
      for the organ specified physicians have been proposed; the International
      Consensus Diagnostic Criteria and the revised clinical diagnostic criteria in
      2011 by Japan Pancreas Society (JPS-2011) for type1 AIP, the Clinical Diagnostic
      Criteria 2012 for IgG4-sclerosing cholangitis (IgG4-SC-2012), the diagnostic
      criteria for IgG4-positive Mikulicz's disease by the Japanse Society for
      Sjogren's syndrome, and Diagnostic criteria for IgG4-related kidney disease by
      the Japanese Society of Nephrology. Although the pathogenic mechanism still
      remains unclear, we have proposed a hypothesis of the pathogenic mechanism;
      abnormal innate and acquired immunity, regulatory T cells, and B cells on
      abnormal genetic backgrounds may be involved in the development of IgG4
      cholangiopathy. Further studies are necessary to clarify the pathogenesis
      including genetic backgrounds, disease specific antigens, and the role of IgG4. 

PMID- 24727876
TI  - Endoscopic ultrasonography for diagnosis and staging of pancreatic
      adenocarcinoma: key messages for clinicians.
AB  - Endoscopic ultrasound (EUS) is a technique that combines the potential of
      endoscopy, which enables the visual examination of the mucosal surface of any
      gastrointestinal (GI) tract, with ultrasonography. Despite diagnostic and
      therapeutic advance, pancreatic cancer (PC), in particular ductal adenocarcinoma,
      remains the most deadly of all GI malignancies, with a 5-years survival rate less
      than 1.8%. Moreover its incidence appears to be increasing and most patients
      present with advanced cancer either locally or with metastatic spread. Thus, all
      efforts must be oriented towards the need of an early diagnosis and to reliably
      identify patients who really can benefit from major surgical interventions. To
      date the most accurate imaging techniques for PC diagnosis and staging remain
      contrast-enhanced computed tomography and EUS. While the former should be the
      first choice in patients with suspected PC, EUS has the highest accuracy in
      detecting small lesions, in assessing tumor size and lymph nodes involvement. The
      possibility to obtain samples from suspicious lesions or lymph nodes, by means of
      EUS-guided fine-needle aspiration, makes this procedure an ideal staging modality
      for PC. Since an accurate preoperative evaluation is essential to choose the
      correct management strategy, EUS role is crucial. 

PMID- 24727877
TI  - Prevention of post-ERCP pancreatitis.
AB  - Over the last 10-15 years there have been refinements in the understanding of
      risk factors for development of acute post-ERCP pancreatitis (PEP). These risk
      factors can be divided into patient risks and procedural risks. The most basic
      way to prevent PEP is avoidance of purely diagnostic ERCP and low-probability
      ERCP for bile duct stones by use of non-invasive or less-invasive imaging
      procedures. Improvement in cannulation techniques has led to a reduction in PEP.
      Placement of prophylactic pancreatic stents and, more recently, use of rectally
      administered non-steroidal anti-inflammatory agents (NSAIDs) has further reduced
      the risk of PEP in high-risk patients and/or following high-risk procedures. In
      this review the methods for prevention of PEP will be discussed. 

PMID- 24727878
TI  - Identification of candidate serum biomarkers for small cell lung cancer by
      proteomics analysis.
AB  - AIM: Detection of novel tumor biomarker will aid in diagnosis of early-stage
      small cell lung cancer (SCLC). The purpose of this study was to identify novel
      tumor biomarker in serum from patients with SCLC using a proteomics-based
      approach. METHODS: Sera were analyzed before the initiation of chemotherapy.
      Serum proteins of SCLC patients and healthy controls were collected and separated
      by 2-D fluorescence differential gel electrophoresis (2-D DIGE). Positive spots
      were analyzed by LC-MS/MS. Different expression of identified biomarker was
      verified by immunohistochemical method in wax specimen from 40 patients. RESULTS:
      A total of 86 proteins were shown to be differentially abundant between the serum
      of SCLC patients and normal subjects by 2-D DIGE. Fifteen proteins were
      identified by LC-MS/MS. According to the bioinformatic analysis, these proteins
      are mainly involved in development and carcinogenesis. Some of them have been
      previously demonstrated to be important prognostic factors. Differential
      expression of 5 proteins between the normal tissue and cancerious tissue was
      confirmed by immunochemistry of SCLC patients. CONCLUSION: We have identified
      different serum proteins between SCLC patients and healthy controls. These
      proteins may be potential serum biomarkers for early detection of SCLC and play a
      role in the development and metastasis of SCLC.

PMID- 24727879
TI  - Comparison of laboratory findings in patients with glomerulonephritis classified
      according to histopathologic diagnosis.
AB  - AIM: The aim of the present study was to assess whether laboratory investigations
      have predictional values for histopathological diagnosis of glomerulonephritis
      before performing renal biopsy. METHODS: The study enrolled 452 patients, who
      underwent kidney biopsy and were examined retrospectively; 128 patients with the
      histopathological diagnosis of glomerulonephritis were included in the study.
      Serum CRP, albumin, uric acid levels, 24 hour urine protein presence, leucocyte
      count, C3, C4, IgG, IgA and IgM levels were assessed. RESULTS: The most common
      diagnosis of glomerulonephritis was IgAN with the percentage of 29.7% within the
      groups. Male gender was predominant except lupus group. Only the ones with
      crescentic glomerulonephritis had higher CRP levels. In 20% of patients with
      IgAN, in 8.3% of the ones with MN, in 35% of crescentic group, in 42% of FSGS
      group, in 30% of patients with MPGN and in 33% of the ones with lupus nephritis
      uric acid levels were found as elevated. In IgAN, FSGS and lupus nephritis
      normoalbuminemia and nephritic proteinuria, in MN and crescentic
      glomerulonephritis hypoalbuminemia, nephrotic proteinuria, in MPGN
      hypoalbuminemia, nephritic proteinuria were established. Serum Ig G levels were
      lower in MN and MPGN. Serum IgA levels were found as elevated in IgAN. Serum C4
      levels were found as lower in lupus nephritis and MPGN. CONCLUSION: In patients
      admitted in clinical picture of glomerulopathy, since measurements of serum CRP,
      albumin, uric acid, C3, C4,IgG, IgA, IgM levels, leucocyte count and 24 hour
      urine protein amount can lead to predict the histopathological diagnosis, their
      significance in routine investigations has been suggested also in our study.

PMID- 24727880
TI  - Automated 3D segmentation of hippocampus based on active appearance model of
      brain MR images for the early diagnosis of Alzheimer's disease.
AB  - AIM: To investigate the hippocampal regional deformation modes by means of a
      novel method of automatic segmentation for discriminating between Alzheimer's
      disease (AD) and normal aging; and to further provide the effective evidence for
      the early diagnosis of AD. METHODS: Twenty AD patients and sixty healthy
      volunteers were included in this retrospective study. High-resolution structural
      volumetric images were obtained on a 3.0 T MR imaging system. Data were processed
      to create three-dimensional (3D) active appearance model (AAM) of hippocampus.
      Automatic recognition and 3D segmentation were carried out on both sides of the
      hippocampus in brain MR images of individuals with this model, and the
      hippocampal statistical shape model was established for AD group and control
      group. Student's t test was used to identify whether there was difference between
      AD group and control group in the hippocampal regional deformation detected by
      automatic segmentation, and to compare whether there was difference between the
      automated segmentation and the manual tracing for quantifying hippocampal volumes
      on left/right side of the same sex group of healthy volunteers and if there was
      genderwise difference. Pearson's Correlation test was employed to determine
      whether there was a correlation between automated segmentation and manual tracing
      for quantifying hippocampal volumes. RESULTS: No significant difference was
      detected between automated segmentation and manual tracing for quantifying
      hippocampal volumes on left/right side of the same sex group of healthy
      volunteers (P>0.05). Further there was no significant genderwise difference
      (P>0.05). A very strong positive correlation existed between both methods for
      quantifying hippocampal volumes (denoted R(2) near 1.0, P<0.001). Noticeable
      atrophy of bilateral hippocampal head was found among twenty patients with AD
      through statistical shape model compared with control group (P<0.05), especially
      on the left where inward-deformation was significantly found. CONCLUSION: This
      novel method of automated segmentation of the hippocampus based on AAM has been
      found to be reliable and accurate in our study, which may be an alternative to
      manual segmentation. The featured atrophy of hippocampal head can be regarded as
      an important biomarker for the early diagnosis of AD.

PMID- 24727881
TI  - [Effect of AChE and BuChE inhibition by rivastigmin in a group of old-old elderly
      patients with cerebrovascular impairment (SIVD type)].
AB  - AIM: Vascular dementia (VaD) is defined as a loss of cognitive function resulting
      from ischemic, hypoperfusive, or hemorrhagic brain lesions due to cerebrovascular
      disease or cardiovascular pathology. The main types of VaD are: Small Vessel
      Disease Dementia (sVAD), Large vessel disease dementia, hypoperfusive-ischemic
      dementia and hemorragic dementia. The sVAD is divided into two main categories:
      subcortical ischemic vascular dementia (SIVD) and cortical dementia. Currently,
      no drugs are approved for the treatment of VaD. This study aimed to determine
      whether rivastigmine, a second generation cholinesterase inhibitor with
      selectivity for the CNS, with capacity to inhibit both acetylcholinesterase
      (AChE) and butyryl-cholinesterase (BuChE), slows the rate of cognitive decline
      associated with VaD. METHODS: Study subjects were 27 male and 43 female
      outpatients aged 80.03+/-6.53 years, with Mini-Mental State Examination (MMSE)
      score ranging batween 22 and 12, affected by VaD. They were included in the study
      if they were undergoing pharmacological treatment with acetylsalicylic acid 100
      mg for at least six months. Patients were divided into two groups: one group was
      treated with ASA 100 mg and rivastigmine patch 9.5 mg (Rivastigmine group), the
      other just with ASA 100 mg (ASA group). All patients were followed for 6 months,
      with a first evaluation (T0) and a second examination after six mounths of
      treatment (T1). RESULTS: Statistically data proved as the Rivastigmine group
      showed constant values at MMSE, compared with patients of the ASA group who
      experienced decline of their cognitive performances. The same result was found in
      CDR, ADL, GDS and NPI scales. It is remarkable to underline as Rivastigmine
      treated patients had a mean improvement in GDS scales, in comparison with
      patients of the ASA group who showed a worsening of mood. CONCLUSION:
      Rivastigmine-therapy improves cognitive performance in elderly with SIVD.

PMID- 24727882
TI  - Low 25-hydroxyvitamin D3 serum levels and non-alcoholic fatty liver disease.

PMID- 24727883
TI  - Assessment of microRNAs in patients with unstable angina pectoris.
AB  - AIMS: While cardiac troponin measurements have significantly improved the early
      diagnosis of myocardial infarction, the timely biomarker-based diagnosis of
      unstable angina pectoris (UAP) remains a major unmet clinical challenge. The aim
      of this study was to assess levels of circulating microRNAs (miRNAs) as possible
      novel biomarkers in patients with UAP. METHODS AND RESULTS: A three-phase
      approach was conducted, comprising (i) profiling of miRNAs in patients with UAP
      and controls groups; (ii) replication of significant miRNAs in an independent
      patient cohort, (iii) validation of a multi-miRNAs panel in a third cohort. Out
      of 25 miRNAs selected for replication, 8 miRNAs remained significantly associated
      with UAP. In a validation phase, a miRNA panel including miR-132, miR-150, and
      miR-186 showed the highest discriminatory power [area under the receiver
      operating-characteristic curve (AUC): 0.91; CI: 0.84-0.98]. CONCLUSION: Using a
      profiling-replication-validation model, we identified eight miRNAs, which may
      facilitate the diagnosis of UAP.

PMID- 24727889
TI  - Central hemodynamics and target organ damage in hypertension.
AB  - Recent advances in technology have enabled the noninvasive evaluation of
      pulsatile hemodynamics in the central aorta; namely, central pressure and flow
      measurements. The central blood pressure represents the true load imposed on the
      heart, kidney and brain, and the central blood flow influences the local flow
      into these vital organs. An elevation of the central blood pressure has a direct,
      adverse impact on the target organ and, thus, the cardiovascular prognosis in
      patients with hypertension. A decrease in the central blood flow can cause organ
      dysfunction and failure. The central pressure and flow dynamics were
      conventionally regarded as unidirectional from the heart to the periphery.
      However, current evidence suggests that it should be recognized as a
      bidirectional interplay between the central and peripheral arteries.
      Specifically, the pressure pulse wave is not only transmitted forward to the
      periphery but also reflected backward to the central aorta. The flow pulse wave
      is also composed of the forward and reverse components. Aortic stiffening and
      arteriolar remodeling due to hypertension not only augment the central pressure
      by increasing the wave reflection but also may alter the central bidirectional
      flow, inducing hemodynamic damage/dysfunction in susceptible organs. Therefore,
      central hemodynamic monitoring has the potential to provide a diagnostic and
      therapeutic basis for preventing systemic target organ damage and for offering
      personalized therapy suitable for the arterial properties in each patient with
      hypertension. This brief review will summarize hypothetical mechanisms for the
      association between the central hemodynamics and hypertensive organ damage in the
      heart, kidney and brain. 

PMID- 24727884
TI  - Ticagrelor vs. clopidogrel in patients with non-ST-elevation acute coronary
      syndrome with or without revascularization: results from the PLATO trial.
AB  - AIMS: The optimal platelet inhibition strategy for ACS patients managed without
      revascularization is unknown. We aimed to evaluate efficacy and safety of
      ticagrelor vs. clopidogrel in the non-ST-elevation acute coronary syndrome (NSTE
      ACS) subgroup of the PLATO trial, in the total cohort, and in the subgroups
      managed with and without revascularization within 10 days of randomization.
      METHODS AND RESULTS: We performed a retrospective analysis of the primary
      endpoint of cardiovascular death/myocardial infarction/stroke. Among 18 624 PLATO
      patients, 11 080 (59%) were categorized as NSTE-ACS at randomization. During the
      initial 10 days, 74% had angiography, 46% PCI, and 5% CABG. In NSTE-ACS patients,
      the primary endpoint was reduced with ticagrelor vs. clopidogrel [10.0 vs. 12.3%;
      hazard ratio (HR) 0.83; 95% confidence interval (CI) = 0.74-0.93], as was
      myocardial infarction (6.6 vs. 7.7%; HR 0.86; 95% CI = 0.74-0.99), cardiovascular
      death (3.7 vs. 4.9%; HR 0.77; 95% CI = 0.64-0.93), and all-cause death (4.3 vs.
      5.8%; HR 0.76; 95% CI = 0.64-0.90). Major bleeding rate was similar between
      treatment groups (13.4 vs. 12.6%; HR 1.07; 95% CI = 0.95-1.19), but ticagrelor
      was associated with an increase in non-CABG major bleeding (4.8 vs. 3.8%; HR
      1.28; 95% CI = 1.05-1.56). Within the first 10 days, 5366 (48.4%) patients were
      managed without revascularization. Regardless of revascularization or not,
      ticagrelor consistently reduced the primary outcome (HR 0.86 vs. 0.85,
      interaction P = 0.93), and all-cause death (HR 0.75 vs. 0.73, interaction P =
      0.89) with no significant increase in overall major bleeding. CONCLUSION: In
      patients with NSTE-ACS, benefit of ticagrelor over clopidogrel in reducing
      ischaemic events and total mortality was consistent with the overall PLATO trial,
      independent of actually performed revascularization during the initial 10 days.

PMID- 24727890
TI  - Acute Basilar Artery Occlusion with Underlying High-Grade Basilar Artery
      Stenosis: Multimodal Endovascular Therapy in a Series of Seven Patients.
AB  - PURPOSE: Acute basilar artery occlusion is associated with high rates of major
      morbidity and mortality. In rare cases, the underlying pathology is a high-grade
      stenosis of the basilar artery. We report on a series of seven cases with
      occluded high-grade basilar artery stenosis who received endovascular therapy at
      our center. MATERIAL AND METHODS: Our prospective database since October 2009
      until September 2013 was screened for patients with acute basilar artery
      occlusion and underlying high-grade stenosis who underwent endovascular therapy.
      Case files were retrospectively reviewed for clinical, outcome, and technical
      data. RESULTS: Seven patients were identified who suffered from an acute basilar
      artery occlusion based on a high-grade stenosis between October 2009 and
      September 2013. These patients were treated with an acute stenting of the basilar
      artery with or without a preceding mechanical thrombectomy. Median age was 75 (53
      83) years; median prethrombectomy National Institute of Health Stroke scale score
      was 19 (7-28). A successful recanalization result defined as modified
      Thrombolysis In Cerebral Infarction grade 2b or higher was achieved in all cases.
      Two of the seven patients had a procedural complication consisting of a vessel
      dissection after angioplasty. A good clinical outcome according to the Solitaire
      flow restoration device versus the Merci Retriever in patients with acute
      ischaemic stroke (SWIFT) study criteria was achieved in three of the seven
      patients. One patient died during hospitalization in the acute phase. CONCLUSION:
      Mechanical thrombectomy combined with acute stenting of the basilar artery is
      technically feasible and may be an effective therapeutic option in the rare case
      of an acutely occluded high-grade stenosis of the basilar artery in patients with
      an otherwise poor prognosis.

PMID- 24727891
TI  - Semaphorin 3A upregulates FOXO 3a-dependent MelCAM expression leading to
      attenuation of breast tumor growth and angiogenesis.
AB  - Semaphorin 3A (Sema 3A), a member of semaphorin family, serves as a guidance clue
      during embryonic development and is known as a candidate tumor suppressor that
      attenuates breast tumor progression by binding with its co-receptor, neuropilin-1
      (NRP-1). However, the underlying mechanism by which Sema 3A suppresses breast
      tumor growth is still unexplored. In this study, we report that Sema 3A regulates
      phosphorylation and nuclear translocation of phosphatase and tensin homolog
      (PTEN) and FOXO 3a. Moreover, Sema 3A controls NRP-1-mediated PTEN-dependent FOXO
      3a activation. Overexpression of PTEN and FOXO 3a enhances Sema 3A-induced
      attenuation of breast cancer cell migration. Chromatin immunoprecipitation and
      electrophoretic mobility shift assay data revealed that FOXO 3a regulates MelCAM
      at the transcriptional level. Furthermore, Sema 3A induces NRP-1-mediated MelCAM
      expression through PTEN and FOXO 3a. The data also showed that vascular
      endothelial growth factor-induced angiogenesis is inhibited by Sema 3A. Loss of
      or gain in function study revealed that Sema 3A modulates phosphorylation of PTEN
      and FOXO 3a and expression of MelCAM, leading to suppression of tumor growth and
      angiogenesis using in vivo mice model. Clinical specimen analysis revealed that
      reduced expression of Sema 3A and p-PTEN are correlated with enhanced breast
      cancer progression, further strengthening our in vitro and in vivo findings.
      Correlation of relapse-free survival of breast cancer patients (n=2878) with
      expression levels of Sema 3A, NRP-1, FOXO 3a and MelCAM were studied by Kaplan
      Meier analysis. Statistical analysis revealed a close association between reduced
      expression of Sema 3A and MelCAM with that of poor patient's survival. Our study
      demonstrated a novel mechanism of regulation of tumor suppression by Sema 3A in
      coordination with a chain of tumor-suppressor genes, which in turn inhibits
      breast cancer cell migration, tumor growth and angiogenesis. 

PMID- 24727892
TI  - CD58, a novel surface marker, promotes self-renewal of tumor-initiating cells in
      colorectal cancer.
AB  - Colorectal tumor-initiating cells (CT-ICs) have self-renewal capabilities and
      have an important role in tumorigenesis, metastasis, recurrence and treatment
      resistance in colorectal cancer. Multiple cell-surface molecules targeting CT
      ICs, possibly representing different CT-IC subpopulations, have been reported.
      However, whether new surface markers exist, as well as the mechanisms by which
      the markers regulate self-renewal, remain unclear. In this study, we enriched a
      CT-IC population through a serum-free low-adhesion system in vitro. Within this
      population, we found that CD58 and CD44 were upregulated using a cDNA GeneChip,
      and CD44(high)CD58(high) cancer cells, the common existence of which was
      demonstrated by flow cytometry in multiple colon cancer cell lines and primary
      specimens, exhibited enhanced self-renewal ability, epithelial-mesenchymal
      transition ability and tumorigenicity, both in vitro and in vivo. Furthermore,
      activated CD58 upregulated the Wnt/beta-catenin pathway and thus promoted self
      renewal of CT-ICs; conversely, knockdown of CD58 significantly impaired sphere
      formation and tumor growth. With immunoprecipitation and western blotting
      approaches, CD58 was found to upregulate the Wnt pathway by degradation of
      Dickkopf 3. These results indicate that CD58 is a novel cell-surface marker that
      functionally regulates self-renewal of CT-ICs, which may provide an intriguing
      therapeutic target for the efficient killing and elimination of CT-ICs. 

PMID- 24727893
TI  - Molecular mechanisms of cell death: central implication of ATP synthase in
      mitochondrial permeability transition.
AB  - The term mitochondrial permeability transition (MPT) is commonly used to indicate
      an abrupt increase in the permeability of the inner mitochondrial membrane to low
      molecular weight solutes. Widespread MPT has catastrophic consequences for the
      cell, de facto marking the boundary between cellular life and death. MPT results
      indeed in the structural and functional collapse of mitochondria, an event that
      commits cells to suicide via regulated necrosis or apoptosis. MPT has a central
      role in the etiology of both acute and chronic diseases characterized by the loss
      of post-mitotic cells. Moreover, cancer cells are often relatively insensitive to
      the induction of MPT, underlying their increased resistance to potentially lethal
      cues. Thus, intense efforts have been dedicated not only at the understanding of
      MPT in mechanistic terms, but also at the development of pharmacological MPT
      modulators. In this setting, multiple mitochondrial and extramitochondrial
      proteins have been suspected to critically regulate the MPT. So far, however,
      only peptidylprolyl isomerase F (best known as cyclophilin D) appears to
      constitute a key component of the so-called permeability transition pore complex
      (PTPC), the supramolecular entity that is believed to mediate MPT. Here, after
      reviewing the structural and functional features of the PTPC, we summarize recent
      findings suggesting that another of its core components is represented by the c
      subunit of mitochondrial ATP synthase. 

PMID- 24727895
TI  - Differential involvement of gp130 signalling pathways in modulating tobacco
      carcinogen-induced lung tumourigenesis.
AB  - Interleukin (IL)-6 family cytokines signal exclusively via the gp130 coreceptor,
      and are implicated in smoking-associated lung cancer, the most lethal cancer
      worldwide. However, the role of gp130 signalling pathways in transducing the
      carcinogenic effects of tobacco-related compounds is ill-defined. Here, we report
      that lung tumourigenesis induced by the potent tobacco carcinogen 4
      (methylnitrosamino)-1-(3-pyridyl)-1-butanone (Nicotine-derived Nitrosamine
      Ketone; NNK) is suppressed in gp130(F/F) knock-in mice characterized by the
      contrasting gp130-dependant hypoactivation of extracellular signal-regulated
      kinase mitogen-activated protein kinase (ERK MAPK) and phosphatidylinositol 3
      kinase/Akt, and hyperactivation of signal transducer and activator of
      transcription (STAT)3 signalling cascades. Specifically, in response to NNK, the
      absolute number and size of lung lesions in gp130(F/F) mice were significantly
      reduced compared with gp130(+/+) littermate controls, and associated with lower
      cellular proliferation without any alteration to the level of apoptosis in
      gp130(F/F) lung tumours. At the molecular level, reduced activation of ERK MAPK,
      but not Akt, was observed in lung tumours of gp130(F/F) mice, and corresponded
      with impaired expression of several tumour suppressor genes (for example, Trp53,
      Tsc2). Notably, STAT3 was not activated in the lungs of gp130(+/+) mice by NNK,
      and genetic normalization of STAT3 activation in gp130(F/F):Stat3(-/+) mice had
      no effect on NNK-induced tumourigenesis. The expression of tumour suppressor
      genes was reduced in tumours from current versus never-smoking lung cancer
      patients, and in vitro pharmacological inhibition of ERK MAPK signalling in human
      lung cancer cells abrogated NNK-induced downmodulation of tumour suppressor gene
      expression. Among IL-6 cytokine family members, IL-6 gene expression was
      specifically upregulated by NNK in vitro and in vivo, and inversely correlated
      with tumour suppressor gene expression. Collectively, our data reveal that a key
      molecular mechanism by which NNK promotes tumour cell proliferation during
      tobacco carcinogen-induced lung carcinogenesis is via upregulation of IL-6 and
      the preferential usage of gp130-dependant ERK MAPK signalling to downmodulate
      tumour suppressor gene expression. 

PMID- 24727894
TI  - delta-Catenin, a Wnt/beta-catenin modulator, reveals inducible mutagenesis
      promoting cancer cell survival adaptation and metabolic reprogramming.
AB  - Mutations of Wnt/beta-catenin signaling pathway has essential roles in
      development and cancer. Although beta-catenin and adenomatous polyposis coli
      (APC) gene mutations are well established and are known to drive tumorigenesis,
      discoveries of mutations in other components of the pathway lagged, which hinders
      the understanding of cancer mechanisms. Here we report that delta-catenin (gene
      designation: CTNND2), a primarily neural member of the beta-catenin superfamily
      that promotes canonical Wnt/beta-catenin/LEF-1-mediated transcription, displays
      exonic mutations in human prostate cancer and promotes cancer cell survival
      adaptation and metabolic reprogramming. When overexpressed in cells derived from
      prostate tumor xenografts, delta-catenin gene invariably gives rise to mutations,
      leading to sequence disruptions predicting functional alterations. Ectopic delta
      catenin gene integrating into host chromosomes is locus nonselective. delta
      Catenin mutations promote tumor development in mouse prostate with probasin
      promoter (ARR2PB)-driven, prostate-specific expression of Myc oncogene, whereas
      mutant cells empower survival advantage upon overgrowth and glucose deprivation.
      Reprogramming energy utilization accompanies the downregulation of glucose
      transporter-1 and poly (ADP-ribose) polymerase cleavage while preserving tumor
      type 2 pyruvate kinase expression. delta-Catenin mutations increase beta-catenin
      translocation to the nucleus and hypoxia-inducible factor 1alpha (HIF-1alpha)
      expression. Therefore, introducing delta-catenin mutations is an important
      milestone in prostate cancer metabolic adaptation by modulating beta-catenin and
      HIF-1alpha signaling under glucose shortage to amplify its tumor-promoting
      potential. 

PMID- 24727896
TI  - High performance Si nanowire field-effect-transistors based on a CMOS inverter
      with tunable threshold voltage.
AB  - We successfully fabricated nanowire-based complementary metal-oxide semiconductor
      (NWCMOS) inverter devices by utilizing n- and p-type Si nanowire field-effect
      transistors (NWFETs) via a low-temperature fabrication processing technique. We
      demonstrate that NWCMOS inverter devices can be operated at less than 1 V, a
      significantly lower voltage than that of typical thin-film based complementary
      metal-oxide semiconductor (CMOS) inverter devices. This low-voltage operation was
      accomplished by controlling the threshold voltage of the n-type Si NWFETs through
      effective management of the nanowire (NW) doping concentration, while realizing
      high voltage gain (>10) and ultra-low static power dissipation (<=3 pW) for high
      performance digital inverter devices. This result offers a viable means of
      fabricating high-performance, low-operation voltage, and high-density digital
      logic circuits using a low-temperature fabrication processing technique suitable
      for next-generation flexible electronics. 

PMID- 24727897
TI  - A promising approach to effectively reduce cramp susceptibility in human muscles:
      a randomized, controlled clinical trial.
AB  - BACKGROUND: To investigate if the cramp threshold frequency (CTF) can be altered
      by electrical muscle stimulation in a shortened position. METHODS: A total of 15
      healthy male sport students were randomly allocated to an intervention (IG, n =
      10) and a non-treatment control group (CG, n = 5). Calf muscles of both legs in
      the IG were stimulated equally twice a week over 6 weeks. The protocol was 3*5 s
      on, 10 s off, 150 us impulse width, 30 Hz above the individual CTF, and was at
      85% of the maximal tolerated stimulation energy. One leg was stimulated in a
      shortened position, inducing muscle cramps (CT), while the opposite leg was
      fixated in a neutral position at the ankle, hindering muscle cramps (nCT). CTF
      tests were performed prior to the first and 96 h after the 6(th) (3 w) and 12(th)
      (6 w) training session. RESULTS: After 3 w, the CTF had significantly (p<0.001)
      increased in CT calves from 23.3+/-5.7 Hz to 33.3+/-6.9 Hz, while it remained
      unchanged in nCT (pre: 23.6+/-5.7 Hz, mid: 22.3+/-3.5 Hz) and in both legs of the
      CG (pre: 21.8+/-3.2 Hz, mid: 22.0+/-2.7 Hz). Only CT saw further insignificant
      increases in the CTF. The applied stimulation energy (mA2 * us) positively
      correlated with the effect on the CTF (r = 0.92; p<0.001). CONCLUSIONS: The
      present study may be useful for developing new non-pharmacological strategies to
      reduce cramp susceptibility. TRIAL REGISTRY: German Clinical Trials Register
      DRKS00005312.

PMID- 24727898
TI  - Estimating abundances of interacting species using morphological traits, foraging
      guilds, and habitat.
AB  - We developed a statistical model to estimate the abundances of potentially
      interacting species encountered while conducting point-count surveys at a set of
      ecologically relevant locations - as in a metacommunity of species. In the model
      we assume that abundances of species with similar traits (e.g., body size) are
      potentially correlated and that these correlations, when present, may exist among
      all species or only among functionally related species (such as members of the
      same foraging guild). We also assume that species-specific abundances vary among
      locations owing to systematic and stochastic sources of heterogeneity. For
      example, if abundances differ among locations due to differences in habitat, then
      measures of habitat may be included in the model as covariates. Naturally, the
      quantitative effects of these covariates are assumed to differ among species. Our
      model also accounts for the effects of detectability on the observed counts of
      each species. This aspect of the model is especially important for rare or
      uncommon species that may be difficult to detect in community-level surveys.
      Estimating the detectability of each species requires sampling locations to be
      surveyed repeatedly using different observers or different visits of a single
      observer. As an illustration, we fitted models to species-specific counts of
      birds obtained while sampling an avian community during the breeding season. In
      the analysis we examined whether species abundances appeared to be correlated due
      to similarities in morphological measures (body mass, beak length, tarsus length,
      wing length, tail length) and whether these correlations existed among all
      species or only among species of the same foraging guild. We also used the model
      to estimate the effects of forested area on species abundances and the effects of
      sound power output (as measured by body size) on species detection probabilities.

PMID- 24727899
TI  - Engineering the product profile of a polysialyltransferase.
AB  - Oligo- and polysaccharides have myriad applications as therapeutic reagents from
      glycoconjugate vaccines to matrices for tissue engineering. Polysaccharide length
      may vary over several orders of magnitude and is a critical determinant of both
      their physical properties and biological activities. Therefore, the tailored
      synthesis of oligo- and polysaccharides of defined size is a major goal for
      glycoengineering. By mutagenesis and screening of a bacterial
      polysialyltransferase (polyST), we identified a single-residue switch that
      controls the size distribution of polymeric products. Specific substitutions at
      this site yielded distributive enzymes that synthesize polysaccharides with
      narrow size distribution ideal for glycoengineering applications. Mechanistic
      investigation revealed that the wild-type enzyme has an extended binding site
      that accommodates at least 20 residues of the growing polymer; changes in
      affinity along this binding site allow fine-tuning of the enzyme's product
      distribution. 

PMID- 24727900
TI  - The role of distant mutations and allosteric regulation on LovD active site
      dynamics.
AB  - Natural enzymes have evolved to perform their cellular functions under complex
      selective pressures, which often require their catalytic activities to be
      regulated by other proteins. We contrasted a natural enzyme, LovD, which acts on
      a protein-bound (LovF) acyl substrate, with a laboratory-generated variant that
      was transformed by directed evolution to accept instead a small free acyl
      thioester and no longer requires the acyl carrier protein. The resulting 29
      mutant variant is 1,000-fold more efficient in the synthesis of the drug
      simvastatin than the wild-type LovD. This is to our knowledge the first nonpatent
      report of the enzyme currently used for the manufacture of simvastatin as well as
      the intermediate evolved variants. Crystal structures and microsecond-scale
      molecular dynamics simulations revealed the mechanism by which the laboratory
      generated mutations free LovD from dependence on protein-protein interactions.
      Mutations markedly altered conformational dynamics of the catalytic residues,
      obviating the need for allosteric modulation by the acyl carrier LovF. 

PMID- 24727901
TI  - Dynamics and hydration explain failed functional transformation in dehalogenase
      design.
AB  - We emphasize the importance of dynamics and hydration for enzymatic catalysis and
      protein design by transplanting the active site from a haloalkane dehalogenase
      with high enantioselectivity to nonselective dehalogenase. Protein
      crystallography confirms that the active site geometry of the redesigned
      dehalogenase matches that of the target, but its enantioselectivity remains low.
      Time-dependent fluorescence shifts and computer simulations revealed that
      dynamics and hydration at the tunnel mouth differ substantially between the
      redesigned and target dehalogenase. 

PMID- 24727902
TI  - Glycobiology: drifting toward polymer perfection.
AB  - The addition of polysialic acid to proteins and cells is emerging as a promising
      therapeutic strategy. Polysialyltransferases synthesize polymers of widely
      varying lengths not optimal for therapeutic reagents, but the development of
      enzyme variants using neutral genetic drift offers a new way to overcome this
      problem.

PMID- 24727904
TI  - Completing the results of the 2013 Boston marathon.
AB  - The 2013 Boston marathon was disrupted by two bombs placed near the finish line.
      The bombs resulted in three deaths and several hundred injuries. Of lesser
      concern, in the immediate aftermath, was the fact that nearly 6,000 runners
      failed to finish the race. We were approached by the marathon's organizers, the
      Boston Athletic Association (BAA), and asked to recommend a procedure for
      projecting finish times for the runners who could not complete the race. With
      assistance from the BAA, we created a dataset consisting of all the runners in
      the 2013 race who reached the halfway point but failed to finish, as well as all
      runners from the 2010 and 2011 Boston marathons. The data consist of split times
      from each of the 5 km sections of the course, as well as the final 2.2 km (from
      40 km to the finish). The statistical objective is to predict the missing split
      times for the runners who failed to finish in 2013. We set this problem in the
      context of the matrix completion problem, examples of which include imputing
      missing data in DNA microarray experiments, and the Netflix prize problem. We
      propose five prediction methods and create a validation dataset to measure their
      performance by mean squared error and other measures. The best method used local
      regression based on a K-nearest-neighbors algorithm (KNN method), though several
      other methods produced results of similar quality. We show how the results were
      used to create projected times for the 2013 runners and discuss potential for
      future application of the same methodology. We present the whole project as an
      example of reproducible research, in that we are able to make the full data and
      all the algorithms we have used publicly available, which may facilitate future
      research extending the methods or proposing completely different approaches. 

PMID- 24727906
TI  - Oxamato-based coordination polymers: recent advances in multifunctional magnetic
      materials.
AB  - The design and synthesis of novel examples of multifunctional magnetic materials
      based on the so-called coordination polymers (CPs) have become very attractive
      for chemists and physicists due to their potential applications in nanoscience
      and nanotechnology. However, their preparation is still an experimental
      challenge, which requires a deep knowledge of coordination chemistry and large
      skills in organic chemistry. The recent advances in this field using a molecular
      programmed approach based on rational self-assembly methods which fully exploit
      the versatility of the coordination chemistry of the barely explored and
      evergreen family of N-substituted aromatic oligo(oxamato) ligands are presented
      in this feature article. These exploratory studies have revealed a wide variety
      of interesting multifunctional magnetic materials such as optically-active chiral
      and luminescent magnets or dynamic porous magnets as candidates for chemical
      sensing. Our feeling, however, is that we have only scratched the surface of the
      topic and that there are many more exciting brand-new molecule-based materials
      waiting to be discovered. 

PMID- 24727905
TI  - An fMRI study of nicotine-deprived smokers' reactivity to smoking cues during
      novel/exciting activity.
AB  - Engaging in novel/exciting ("self-expanding") activities activates the mesolimbic
      dopamine pathway, a brain reward pathway also associated with the rewarding
      effects of nicotine. This suggests that self-expanding activities can potentially
      substitute for the reward from nicotine. We tested this model among nicotine
      deprived smokers who, during fMRI scanning, played a series of two-player
      cooperative games with a relationship partner. Games were randomized in a 2 (self
      expanding vs. not) x 2 (cigarette cue present vs. absent) design. Self-expansion
      conditions yielded significantly greater activation in a reward region (caudate)
      than did non-self-expansion conditions. Moreover, when exposed to smoking cues
      during the self-expanding versus the non-self-expanding cooperative games,
      smokers showed less activation in a cigarette cue-reactivity region, a priori
      defined [temporo-parietal junction (TPJ)] from a recent meta-analysis of cue
      reactivity. In smoking cue conditions, increases in excitement associated with
      the self-expanding condition (versus the non-self-expanding condition) were also
      negatively correlated with TPJ activation. These results support the idea that a
      self-expanding activity promoting reward activation attenuates cigarette cue
      reactivity among nicotine-deprived smokers. Future research could focus on the
      parameters of self-expanding activities that produce this effect, as well as test
      the utility of self-expansion in clinical interventions for smoking cessation. 

PMID- 24727903
TI  - Vitamin d deficiency in a multiethnic healthy control cohort and altered immune
      response in vitamin D deficient European-American healthy controls.
AB  - OBJECTIVE: In recent years, vitamin D has been shown to possess a wide range of
      immunomodulatory effects. Although there is extensive amount of research on
      vitamin D, we lack a comprehensive understanding of the prevalence of vitamin D
      deficiency or the mechanism by which vitamin D regulates the human immune system.
      This study examined the prevalence and correlates of vitamin D deficiency and the
      relationship between vitamin D and the immune system in healthy individuals.
      METHODS: Healthy individuals (n = 774) comprised of European-Americans (EA, n =
      470), African-Americans (AA, n = 125), and Native Americans (NA, n = 179) were
      screened for 25-hydroxyvitamin D [25(OH)D] levels by ELISA. To identify the most
      noticeable effects of vitamin D on the immune system, 20 EA individuals with
      severely deficient (<11.3 ng/mL) and sufficient (>24.8 ng/mL) vitamin D levels
      were matched and selected for further analysis. Serum cytokine level measurement,
      immune cell phenotyping, and phosphoflow cytometry were performed. RESULTS:
      Vitamin D sufficiency was observed in 37.5% of the study cohort. By multivariate
      analysis, AA, NA, and females with a high body mass index (BMI, >30) demonstrate
      higher rates of vitamin D deficiency (p<0.05). Individuals with vitamin D
      deficiency had significantly higher levels of serum GM-CSF (p = 0.04), decreased
      circulating activated CD4+ (p = 0.04) and CD8+ T (p = 0.04) cell frequencies than
      individuals with sufficient vitamin D levels. CONCLUSION: A large portion of
      healthy individuals have vitamin D deficiency. These individuals have altered T
      and B cell responses, indicating that the absence of sufficient vitamin D levels
      could result in undesirable cellular and molecular alterations ultimately
      contributing to immune dysregulation.

PMID- 24727907
TI  - Biofuel purification in zeolitic imidazolate frameworks: the significant role of
      functional groups.
AB  - A molecular simulation study is reported for biofuel purification in six zeolitic
      imidazolate frameworks (ZIF-8, -25, -71, -90, -96 and -97) with different
      functional groups. For pure ethanol and water, the predicted adsorption isotherms
      agree fairly well with experimental data. Hydrogen bonding has an important
      effect on the adsorption of ethanol and water. In hydrophilic ZIFs (ZIF-90, -96
      and -97) with polar groups, adsorption capacities are higher than in hydrophobic
      counterparts (ZIF-8, -25 and -71). The atomic charges in symmetrically
      functionalized ZIF-8, -25, and -71 are found to have an indiscernible effect on
      adsorption, in remarkable contrast to asymmetrically functionalized ZIF-90, -96
      and -97. For ethanol-water mixtures representing the biofuel, the selectivity of
      ethanol-water drops with increasing ethanol in mixtures. It is revealed that the
      selectivity is determined primarily by framework hydrophobicity as well as the
      cage size. Among the six ZIFs, ZIF-8 exhibits the highest selectivity. This
      simulation study provides a microscopic insight into the adsorption of ethanol
      and water in various ZIFs, reveals the significant role of functional groups in
      governing biofuel purification, and would facilitate the development of new
      nanoporous materials for high-efficacy liquid separation. 

PMID- 24727908
TI  - Monte Carlo simulation of light transport in turbid medium with embedded object-
      spherical, cylindrical, ellipsoidal, or cuboidal objects embedded within
      multilayered tissues.
AB  - Monte Carlo modeling of light transport in multilayered tissue (MCML) is modified
      to incorporate objects of various shapes (sphere, ellipsoid, cylinder, or cuboid)
      with a refractive-index mismatched boundary. These geometries would be useful for
      modeling lymph nodes, tumors, blood vessels, capillaries, bones, the head, and
      other body parts. Mesh-based Monte Carlo (MMC) has also been used to compare the
      results from the MCML with embedded objects (MCML-EO). Our simulation assumes a
      realistic tissue model and can also handle the transmission/reflection at the
      object-tissue boundary due to the mismatch of the refractive index. Simulation of
      MCML-EO takes a few seconds, whereas MMC takes nearly an hour for the same
      geometry and optical properties. Contour plots of fluence distribution from MCML
      EO and MMC correlate well. This study assists one to decide on the tool to use
      for modeling light propagation in biological tissue with objects of regular
      shapes embedded in it. For irregular inhomogeneity in the model (tissue), MMC has
      to be used. If the embedded objects (inhomogeneity) are of regular geometry
      (shapes), then MCML-EO is a better option, as simulations like Raman scattering,
      fluorescent imaging, and optical coherence tomography are currently possible only
      with MCML.

PMID- 24727909
TI  - Excitation-scanning hyperspectral imaging microscope.
AB  - Hyperspectral imaging is a versatile tool that has recently been applied to a
      variety of biomedical applications, notably live-cell and whole-tissue signaling.
      Traditional hyperspectral imaging approaches filter the fluorescence emission
      over a broad wavelength range while exciting at a single band. However, these
      emission-scanning approaches have shown reduced sensitivity due to light
      attenuation from spectral filtering. Consequently, emission scanning has limited
      applicability for time-sensitive studies and photosensitive applications. In this
      work, we have developed an excitation-scanning hyperspectral imaging microscope
      that overcomes these limitations by providing high transmission with short
      acquisition times. This is achieved by filtering the fluorescence excitation
      rather than the emission. We tested the efficacy of the excitation-scanning
      microscope in a side-by-side comparison with emission scanning for detection of
      green fluorescent protein (GFP)-expressing endothelial cells in highly
      autofluorescent lung tissue. Excitation scanning provided higher signal-to-noise
      characteristics, as well as shorter acquisition times (300  ms/wavelength band
      with excitation scanning versus 3  s/wavelength band with emission scanning).
      Excitation scanning also provided higher delineation of nuclear and cell borders,
      and increased identification of GFP regions in highly autofluorescent tissue.
      These results demonstrate excitation scanning has utility in a wide range of time
      dependent and photosensitive applications.

PMID- 24727910
TI  - Fast vascular component of cortical spreading depression revealed in rats by
      blood pulsation imaging.
AB  - Cortical spreading depression (CSD) is a slowly propagating wave of
      depolarization of neurons and glia and has a less characterized vascular
      component. CSD is a commonly used phenomenon to test new methods of live brain
      imaging. Application of a blood pulsations imaging (BPI) technique to study of
      CSD induced with high-potassium solution in rat cortex allowed us to visualize
      for the first time the novel vascular component of a CSD wave. In our study, this
      wave component propagated in the limited part of the cortex along the bow-shaped
      trajectory in sharp contrast with concentric development of CSD measured by
      concurrently applied optical intrinsic signal (OIS) imaging technique. It was
      associated with a significant increase of the blood pulsations amplitude (BPA),
      started with a delay of 20 to 90 s comparing to signal measured with OIS, and
      propagated 40% faster than OIS signal. These findings suggest that the BPA and
      slower change of the cerebral blood volume are not directly related to each other
      even though both characterize the same vascular system. Our study indicates that
      the BPI technique could be used for characterization of the new pulsatile
      vascular component of CSDs in animal models of migraine, stroke, and brain
      trauma.

PMID- 24727911
TI  - Germline variation in colorectal risk Loci does not influence treatment effect or
      survival in metastatic colorectal cancer.
AB  - BACKGROUND: Colorectal cancer (CRC) risk is partly conferred by common, low
      penetrance single nucleotide polymorphisms (SNPs). We hypothesized that these
      SNPs are associated with outcomes in metastatic CRC. METHODS: Six candidate SNPs
      from 8q24, 10p14, 15q13, 18q21 were investigated for their association with
      response rate (RR), time to progression (TTP) and overall survival (OS) among 524
      patients treated on a phase III clinical trial of first-line chemotherapy for
      metastatic CRC. RESULTS: rs10795668 was weakly associated with TTP (p = 0.02),
      but not RR or OS. No other SNPs carried statistically significant HRs for any of
      the primary outcomes (RR, TTP or OS). CONCLUSION: Common low-penetrance CRC risk
      SNPs were not associated with outcomes among patients with metastatic CRC.

PMID- 24727931
TI  - A complementary graphical method for reducing and analyzing large data sets. Case
      studies demonstrating thresholds setting and selection.
AB  - OBJECTIVES: Graphical displays can make data more understandable; however, large
      graphs can challenge human comprehension. We have previously described a
      filtering method to provide high-level summary views of large data sets. In this
      paper we demonstrate our method for setting and selecting thresholds to limit
      graph size while retaining important information by applying it to large single
      and paired data sets, taken from patient and bibliographic databases. METHODS:
      Four case studies are used to illustrate our method. The data are either patient
      discharge diagnoses (coded using the International Classification of Diseases,
      Clinical Modifications [ICD9-CM]) or Medline citations (coded using the Medical
      Subject Headings [MeSH]). We use combinations of different thresholds to obtain
      filtered graphs for detailed analysis. The thresholds setting and selection, such
      as thresholds for node counts, class counts, ratio values, p values (for diff
      data sets), and percentiles of selected class count thresholds, are demonstrated
      with details in case studies. The main steps include: data preparation, data
      manipulation, computation, and threshold selection and visualization. We also
      describe the data models for different types of thresholds and the considerations
      for thresholds selection. RESULTS: The filtered graphs are 1%-3% of the size of
      the original graphs. For our case studies, the graphs provide 1) the most heavily
      used ICD9-CM codes, 2) the codes with most patients in a research hospital in
      2011, 3) a profile of publications on "heavily represented topics" in MEDLINE in
      2011, and 4) validated knowledge about adverse effects of the medication of
      rosiglitazone and new interesting areas in the ICD9-CM hierarchy associated with
      patients taking the medication of pioglitazone. CONCLUSIONS: Our filtering method
      reduces large graphs to a manageable size by removing relatively unimportant
      nodes. The graphical method provides summary views based on computation of usage
      frequency and semantic context of hierarchical terminology. The method is
      applicable to large data sets (such as a hundred thousand records or more) and
      can be used to generate new hypotheses from data sets coded with hierarchical
      terminologies.

PMID- 24727912
TI  - Lack of clinical manifestations in asymptomatic dengue infection is attributed to
      broad down-regulation and selective up-regulation of host defence response genes.
AB  - OBJECTIVES: Dengue represents one of the most serious life-threatening vector
      borne infectious diseases that afflicts approximately 50 million people across
      the globe annually. Whilst symptomatic infections are frequently reported,
      asymptomatic dengue remains largely unnoticed. Therefore, we sought to
      investigate the immune correlates conferring protection to individuals that
      remain clinically asymptomatic. METHODS: We determined the levels of neutralizing
      antibodies (nAbs) and gene expression profiles of host immune factors in
      individuals with asymptomatic infections, and whose cognate household members
      showed symptoms consistent to clinical dengue infection. RESULTS: We observed
      broad down-regulation of host defense response (innate, adaptive and matrix
      metalloprotease) genes in asymptomatic individuals as against symptomatic
      patients, with selective up-regulation of distinct genes that have been
      associated with protection. Selected down-regulated genes include: TNF alpha
      (TNF), IL8, C1S, factor B (CFB), IL2, IL3, IL4, IL5, IL8, IL9, IL10 and IL13,
      CD80, CD28, and IL18, MMP8, MMP10, MMP12, MMP15, MMP16, and MMP24. Selected up
      regulated genes include: RANTES (CCL5), MIP-1alpha (CCL3L1/CCL3L3), MIP-1beta
      (CCL4L1), TGFbeta (TGFB), and TIMP1. CONCLUSION: Our findings highlight the
      potential association of certain host genes conferring protection against
      clinical dengue. These data are valuable to better explore the mysteries behind
      the hitherto poorly understood immunopathogenesis of subclinical dengue
      infection.

PMID- 24727932
TI  - The structure of ferricytochrome c552 from the psychrophilic marine bacterium
      Colwellia psychrerythraea 34H.
AB  - Approximately 40% of all proteins are metalloproteins, and approximately 80% of
      Earth's ecosystems are at temperatures <=5  degrees C, including 90% of the
      global ocean. Thus, an essential aspect of marine metallobiochemistry is an
      understanding of the structure, dynamics, and mechanisms of cold adaptation of
      metalloproteins from marine microorganisms. Here, the molecular structure of the
      electron-transfer protein cytochrome c552 from the psychrophilic marine bacterium
      Colwellia psychrerythraea 34H has been determined by X-ray crystallography (PDB:
      ). The structure is highly superimposable with that of the homologous cytochrome
      from the mesophile Marinobacter hydrocarbonoclasticus. Based on structural
      analysis and comparison of psychrophilic, psychrotolerant, and mesophilic
      sequences, a methionine-based ligand-substitution mechanism for psychrophilic
      protein stabilization is proposed.

PMID- 24727933
TI  - Major and Minor League Baseball Hamstring Injuries: Epidemiologic Findings From
      the Major League Baseball Injury Surveillance System.
AB  - BACKGROUND: Hamstring strains are a recognized cause of disability for athletes
      in many sports, but no study exists that reports the incidence and circumstances
      surrounding these injuries in professional baseball. HYPOTHESIS: Professional
      baseball players have a high incidence of hamstring strains, and these injuries
      are influenced by multiple factors including history of hamstring injury, time
      period within the season, and activity of base running. STUDY DESIGN: Descriptive
      epidemiologic study. METHODS: For the 2011 season, injury data were prospectively
      collected for every Major League Baseball (MLB) major and minor league team and
      recorded in the MLB's Injury Surveillance System. Data collected for this study
      included date of injury, activity in which the player was engaged at the time of
      injury, and time loss. Injury rates were reported in injuries per athlete
      exposure (A-E). Athlete-exposures were defined as the average number of players
      on a team who were participating in a game multiplied by the number of games.
      RESULTS: In the major leagues, 50 hamstring strains were reported for an injury
      rate (IR) of 0.7 per 1000 A-Es and averaged 24 days missed. In the minor leagues,
      218 hamstring strains were reported for an IR of 0.7 per 1000 A-Es and averaged
      27 days missed. Base running, specifically running to first base, was the top
      activity for sustaining a hamstring strain in both major and minor leagues,
      associated with almost two-thirds of hamstring strains. Approximately two-thirds
      of these injuries in both the major and minor leagues resulted in more than 7
      days of time loss. Approximately 25% of these injuries kept the player out for 1
      month or longer. History of a previous hamstring strain in the prior year, 2010,
      was found in 20% of the major league players and 8% of the minor league players.
      In the major leagues, the month of May had a statistically significant higher
      frequency of hamstring injuries than any other month in the season (P = .0153).
      CONCLUSION: Hamstring strains are a considerable cause of disability in
      professional baseball and are affected by history of hamstring strain, seasonal
      timing, and running to first base.

PMID- 24727934
TI  - Age-Related Differences in Anterior Cruciate Ligament Remnant Vascular-Derived
      Cells.
AB  - BACKGROUND: The anterior cruciate ligament (ACL) does not heal spontaneously
      after injury, and patients of different ages respond differently to treatment.
      CD34+ stem/progenitor cells derived from the ACL remnant and associated tissues
      contribute to tendon-bone healing, but the relationship between age and the ACL's
      healing potential has not been clarified. HYPOTHESIS: The ACL remnant and
      associated tissues from adolescent patients have more CD34+ cells, and this
      population of cells from younger patients exhibits a higher potential for
      proliferation and differentiation in vitro. STUDY DESIGN: Descriptive laboratory
      study. METHODS: Ruptured ACL remnants and associated tissues were harvested from
      28 patients (mean age, 24.6 +/- 1.6 years) who had undergone primary arthroscopic
      ACL reconstruction. Patients were divided into 3 patient groups by age: 10-19
      years (teens group; n = 10), 20-29 years (20s group; n = 10), and >=30 years (30s
      group; n = 8). The ACL remnant cells were characterized using fluorescence
      activated cell sorting (FACS). Expansion potential was evaluated using population
      doubling (PD), and multilineage differentiation potential was assessed and
      compared. RESULTS: The FACS analysis showed numerous CD34+ cells in the teens
      group compared with the 30s group (mean, 25.4% +/- 7.9% vs 16.9% +/- 3.9%,
      respectively; P = .044). The PD results indicated that the teens group had a
      significantly higher expansion potential than the 30s group at passage 3 (mean,
      3.3 +/- 0.2 vs 2.8 +/- 0.2, respectively; P = .039). Young ACL remnant cells had
      a higher potential for osteogenic differentiation according to alkaline
      phosphatase activity (teens group, 169.5 +/- 37.9 * 10 ng/mL vs 30s group, 64.9
      +/- 14.6 * 10 ng/mL; P = .029) and osteocalcin gene expression (teens group, 1.0
      +/- 0.25 vs 30s group, 0.39 +/- 0.01; P = .01). In addition, the teens group
      displayed a higher differentiation potential to angiogenic lineages (acetylated
      low-density lipoprotein/Ulex europaeus lectin-stained cell counts) than other
      groups (teens group, 15.9 +/- 1.9 vs 20s group, 8.9 +/- 1.3 [P = .04]; teens
      group, 15.9 +/- 1.9 vs 30s group, 7.2 +/- 1.5 [P = .008]) and also tube length
      (teens group, 6939 +/- 470 MUm vs 30s group, 4119 +/- 507 MUm; P = .009).
      CONCLUSION: The ACL remnants of adolescent patients had more CD34+ cells, and
      those cells had a higher potential for proliferation and multilineage
      differentiation in vitro. CLINICAL RELEVANCE: During remnant-preserving or
      remnant-transplanted ACL reconstruction, surgeons should consider the patient's
      age when predicting the healing potential.

PMID- 24727935
TI  - Recovery of donor hearts after circulatory death with normothermic extracorporeal
      machine perfusion.
AB  - OBJECTIVES: A severe donor organ shortage leads to the death of a substantial
      number of patients who are listed for transplantation. The use of hearts from
      donors after circulatory death could significantly expand the donor organ pool,
      but due to concerns about their viability, these are currently not used for
      transplantation. We propose short-term ex vivo normothermic machine perfusion
      (MP) to improve the viability of these ischaemic donor hearts. METHODS: Hearts
      from male Lewis rats were subjected to 25 min of global in situ warm ischaemia
      (WI) (37 degrees C), explanted, reconditioned for 60 min with normothermic (37
      degrees C) MP with diluted autologous blood and then stored for 4 h at 0-4
      degrees C in Custodiol cold preservation solution. Fresh and ischaemic hearts
      stored for 4 h in Custodiol were used as controls. Graft function was assessed in
      a blood-perfused Langendorff circuit. RESULTS: During reconditioning, both the
      electrical activity and contractility of the ischaemic hearts recovered rapidly.
      Throughout the Langendorff reperfusion, the reconditioned ischaemic hearts had a
      higher average heart rate and better contractility compared with untreated
      ischaemic controls. Moreover, the reconditioned ischaemic hearts had higher
      tissue adenosine triphosphate levels and a trend towards improved tissue redox
      state. Perfusate levels of troponin T, creatine kinase and lactate dehydrogenase
      were not significantly lower than those of untreated ischaemic controls. The
      micro- and macroscopic appearance of the reconditioned ischaemic hearts were
      improved compared with ischaemic controls, but in both groups myocardial damage
      and oedema were evident. CONCLUSIONS: Our results indicate that functional
      recovery from global WI is possible during short-term ex vivo reperfusion,
      allowing subsequent cold storage without compromising organ viability. We expect
      that once refined and validated, this approach may enable safe transplantation of
      hearts obtained from donation after circulatory death.

PMID- 24727936
TI  - Ribosomal RNA gene repeats, their stability and cellular senescence.
AB  - The ribosomal RNA gene (rDNA) repeats form a historically well-researched region
      in the chromosome. Their highly repetitive structure can be identified easily
      which has enabled studies on DNA replication, recombination, and transcription.
      The region is one of the most unstable regions in the genome because of
      deleterious recombination among the repeats. The ribosomal RNA gene repeats use a
      unique gene amplification system to restore the copy number after this has been
      reduced due to recombination. It has been shown that unstable features in the
      genome can accelerate cellular senescence that restricts the lifespan of a cell.
      Here, I will introduce a study by our group that shows how the stability of rDNA
      is maintained and affects lifespan. I propose that the ribosomal RNA gene repeats
      constitute a center from which the stability of the whole genome is regulated and
      the lifespan of the cell is controlled. 

PMID- 24727938
TI  - Joint estimation of phase and phase diffusion for quantum metrology.
AB  - Phase estimation, at the heart of many quantum metrology and communication
      schemes, can be strongly affected by noise, whose amplitude may not be known, or
      might be subject to drift. Here we investigate the joint estimation of a phase
      shift and the amplitude of phase diffusion at the quantum limit. For several
      relevant instances, this multiparameter estimation problem can be effectively
      reshaped as a two-dimensional Hilbert space model, encompassing the description
      of an interferometer phase probed with relevant quantum states--split single
      photons, coherent states or N00N states. For these cases, we obtain a trade-off
      bound on the statistical variances for the joint estimation of phase and phase
      diffusion, as well as optimum measurement schemes. We use this bound to quantify
      the effectiveness of an actual experimental set-up for joint parameter estimation
      for polarimetry. We conclude by discussing the form of the trade-off relations
      for more general states and measurements.

PMID- 24727937
TI  - Biosynthesis and deficiencies of glycosylphosphatidylinositol.
AB  - At least 150 different human proteins are anchored to the outer leaflet of the
      plasma membrane via glycosylphosphatidylinositol (GPI). GPI preassembled in the
      endoplasmic reticulum is attached to the protein's carboxyl-terminus as a post
      translational modification by GPI transamidase. Twenty-two PIG (for Phosphatidyl
      Inositol Glycan) genes are involved in the biosynthesis and protein-attachment of
      GPI. After attachment to proteins, both lipid and glycan moieties of GPI are
      structurally remodeled in the endoplasmic reticulum and Golgi apparatus. Four
      PGAP (for Post GPI Attachment to Proteins) genes are involved in the remodeling
      of GPI. GPI-anchor deficiencies caused by somatic and germline mutations in the
      PIG and PGAP genes have been found and characterized. The characteristics of the
      26 PIG and PGAP genes and the GPI deficiencies caused by mutations in these genes
      are reviewed. 

PMID- 24727939
TI  - Ginsenoside compound K suppresses the abnormal activation of T lymphocytes in
      mice with collagen-induced arthritis.
AB  - AIM: To investigate the anti-arthritis and immunomodulatory activities of
      ginsenoside compound K (C-K) in mice with collagen-induced arthritis (CIA).
      METHODS: DBA/1 mice with CIA were treated with C-K (28, 56 or 112 mg.kg(-1).d(
      1), ig) or the positive control methotrexate (2 mg/kg, ig, every 3 d) for 34 d.
      Splenic T and B lymphocytes were positively isolated using anti-CD3-coated
      magnetic beads or a pan B cell isolation kit. T lymphocyte subsets, and CD28, T
      cell receptor (TCR), cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) and
      programmed death-1 (PD-1) expression in purified splenic T lymphocytes were
      analyzed using flow cytometry, Western blotting and laser confocal microscopy.
      RESULTS: C-K treatment significantly ameliorated the pathologic manifestations of
      CIA mice, remarkably inhibited T lymphocyte proliferation, and marginally
      inhibited the proliferation of B lymphocytes. C-K treatment significantly
      suppressed TNF-alpha and anti-CII antibody levels, and increased IFN-gamma level
      in the joints of CIA mice, but did not alter IL-4 production. Treatment of CIA
      mice with C-K significantly decreased the percentages of activated T cells, co
      stimulatory molecule-expressing T cells and effector memory T cells, and
      increased the frequencies of naive T cells and regulatory T cells. Furthermore, C
      K treatment significantly decreased the expression of CD28 and TCR, whereas it
      increased the expression of CTLA-4 and PD-1 on T lymphocytes of CIA mice.
      Methotrexate treatment exerted comparable effects in all these experiments.
      CONCLUSION: C-K suppresses the progression of CIA through regulating TCR, CD28,
      CTLA-4 and PD-1 expression, thus inhibiting the abnormal activation and
      differentiation of T lymphocytes.

PMID- 24727940
TI  - Human umbilical cord blood mesenchymal stem cell transplantation suppresses
      inflammatory responses and neuronal apoptosis during early stage of focal
      cerebral ischemia in rabbits.
AB  - AIM: Human umbilical cord blood mesenchymal stem cells (hUCB-MSCs) have been
      shown to ameliorate cerebral ischemia in animal models. In this study we
      investigated the effects of hUCB-MSCs on inflammatory responses and neuronal
      apoptosis during the early stage of focal cerebral ischemia in rabbits. METHODS:
      Focal cerebral ischemia was induced in male New Zealand rabbits by occlusion of
      MCA for 2 h. The blood samples were collected at different time points prior and
      during MCAO-reperfusion. The animals were euthanized 3 d after MCAO, and the
      protein levels of IL-1beta, IL-6, IL-10 and TNF-alpha in the serum and peri
      ischemic brain tissues were detected using Western blot and ELISA, respectively.
      Inflammatory cell infiltration, neuronal apoptosis and neuronal density were
      measured morphologically. hUCB-MSCs (5 * 10(6)) were iv injected a few minutes
      after MCAO. RESULTS: The serum levels of IL-1beta, IL-6 and TNF-alpha were
      rapidly increased, and peaked at 2 h after the start of MCAO. hUCB-MSC
      transplantation markedly and progressively suppressed the ischemia-induced
      increases of serum IL-1beta, IL-6 and TNF-alpha levels within 6 h MCAO
      reperfusion. Focal cerebral ischemia decreased the serum level of IL-10, which
      was prevented by hUCB-MSC transplantation. The expression of IL-1beta, IL-6, IL
      10 and TNF-alpha in the peri-ischemic brain tissues showed similar changes as in
      the serum. hUCB-MSC transplantation markedly suppressed the infiltration of
      inflammatory cells, and increased the neuronal density around the ischemic
      region. Furthermore, hUCB-MSC transplantation significantly decreased the
      percentage of apoptosis around the ischemic region. CONCLUSION: hUCB-MSCs
      transplantation suppresses inflammatory responses and neuronal apoptosis during
      the early stage focal cerebral ischemia in rabbits.

PMID- 24727942
TI  - Ultrasound cardiac calcium assessment.

PMID- 24727943
TI  - Slow excited state phototautomerization in 3-hydroxyisoquinoline.
AB  - In the present work we report the spectral and photophysical properties of 3
      hydroxyisoquinoline in various protic/aprotic solvents. Our steady state and time
      resolved fluorescence data indicates that in the monomer form of 3HIQ
      phototautomerization can take place in the excited state through excited state
      intramolecular proton, while as per earlier suggestions phototautomerization in
      3HIQ occurs in dimer or complex (in the presence of acetic acid) form. Moreover,
      we find rather slow tautomerization (occurring on the nanosecond scale). It is
      found that proton transfer occurs both in the ground as well as excited states
      and is controlled by the polarity of the solvent. 

PMID- 24727941
TI  - Chloroquine potentiates the anti-cancer effect of lidamycin on non-small cell
      lung cancer cells in vitro.
AB  - AIM: To assess the synergistic actions of lidamycin (LDM) and chloroquine (CQ), a
      lysosomal enzyme inhibitor, in human non-small cell lung cancer (NSCLC) cells,
      and to elucidate the potential mechanisms. METHODS: Human NSCLC cell lines A549
      and H460 were treated with CQ and/or LDM. Cell proliferation was analyzed using
      MTT assay, and apoptosis was quantified using flow cytometry. Western blotting
      was used to detect the protein levels of caspase 3, PARP, Bcl-2, Bax, p53, LC3-I
      and LC3-II. A H460 cell xenograft model in BALB/c nude mice was used to evaluate
      the anticancer efficacy of CQ and LDM in vivo. RESULTS: Both LDM and CQ
      concentration-dependently suppressed the proliferation of A549 and H460 cells in
      vitro (the IC50 values of LDM were 1.70 +/- 0.75 and 0.043 +/- 0.026 nmol/L,
      respectively, while the IC50 values of CQ were 71.3 +/- 6.1 and 55.6 +/- 12.5
      MUmol/L, respectively). CQ sensitized both NSCLC cell lines to LDM, and the
      majority of the coefficients of drug interaction (CDIs) for combination-doses
      were less than 1. The ratio of apoptosis of H460 cells induced by a combined
      treatment of CQ and LDM (77.0% +/- 5.2%) was significantly higher than those
      caused by CQ (23.1% +/- 4.2%) or by LDM (65.1% +/- 4.1%) alone. Furthermore, the
      combined treatment markedly increased the cleaved PARP and cleaved caspase 3 in
      H460 cells, which were partly reversed by pretreatment with the caspase inhibitor
      zVAD.fmk. zVAD.fmk also partially reversed the inhibitory effect of the
      combination treatment on the proliferation of H460 cells. The combination therapy
      group had a notable increase in expression of Bax and a very slight decrease in
      expression of Bcl-2 and p53 protein. LDM alone scarcely affected the level of LC3
      II in H460 cells, but slightly reduced CQ-induced LC3-II expression. 3-MA, an
      autophagy inhibitor also sensitized H460 cells to LDM. In nude mice bearing H460
      cell xenograft, administration of LDM (25 MUg/kg, iv) and CQ (60 mg/kg, ip)
      suppressed tumor growth by 57.14% and 73.02%, respectively. CONCLUSION: The
      synergistic anticancer effect of LDM and CQ in vitro results from activation of a
      caspase-dependent and p53-independent apoptosis pathway as well as inhibition of
      cytoprotective autophagy.

PMID- 24727944
TI  - Temporally and spatially constrained ICA of fMRI data analysis.
AB  - Constrained independent component analysis (CICA) is capable of eliminating the
      order ambiguity that is found in the standard ICA and extracting the desired
      independent components by incorporating prior information into the ICA contrast
      function. However, the current CICA method produces constraints that are based on
      only one type of prior information (temporal/spatial), which may increase the
      dependency of CICA on the accuracy of the prior information. To improve the
      robustness of CICA and to reduce the impact of the accuracy of prior information
      on CICA, we proposed a temporally and spatially constrained ICA (TSCICA) method
      that incorporated two types of prior information, both temporal and spatial, as
      constraints in the ICA. The proposed approach was tested using simulated fMRI
      data and was applied to a real fMRI experiment using 13 subjects who performed a
      movement task. Additionally, the performance of TSCICA was compared with the ICA
      method, the temporally CICA (TCICA) method and the spatially CICA (SCICA) method.
      The results from the simulation and from the real fMRI data demonstrated that
      TSCICA outperformed TCICA, SCICA and ICA in terms of robustness to noise.
      Moreover, the TSCICA method displayed better robustness to prior temporal/spatial
      information than the TCICA/SCICA method. 

PMID- 24727945
TI  - Maternal inflammation modulates infant immune response patterns to viral lung
      challenge in a murine model.
AB  - BACKGROUND: Chorioamnionitis, an inflammatory gestational disorder, commonly
      precedes preterm delivery. Preterm infants may be at particular risk for
      inflammation-related morbidity related to infection, although the pathogenic
      mechanisms are unclear. We hypothesized that maternal inflammation modulates
      immune programming to drive postnatal inflammatory processes. METHODS: We used a
      novel combined murine model to treat late gestation dams with low-dose
      lipopolysaccharide (LPS) and to secondarily challenge exposed neonates or
      weanlings with Sendai virus (SeV) lung infection. Multiple organs were analyzed
      to characterize age-specific postnatal immune and inflammatory responses.
      RESULTS: Maternal LPS treatment enhanced innate immune populations in the lungs,
      livers, and/or spleens of exposed neonates or weanlings. Secondary lung SeV
      infection variably affected neutrophil, macrophage, and dendritic cell
      proportions in multiple organs of exposed pups. Neonatal lung infection induced
      brain interleukin (IL)-4 expression, although this response was muted in LPS
      exposed pups. Adaptive immune cells, including lung, lymph node, and thymic
      lymphocytes and lung CD4 cells expressing FoxP3, interferon (IFN)-gamma, or IL
      17, were variably prominent in LPS-exposed pups. CONCLUSION: Maternal
      inflammation modifies postnatal immunity and augments systemic inflammatory
      responses to viral lung infection in an age-specific manner. We speculate that
      inflammatory modulation of the developing immune system contributes to chronic
      morbidity and mortality in preterm infants.

PMID- 24727946
TI  - Aquaporin-4 polymorphisms and brain/body weight ratio in sudden infant death
      syndrome (SIDS).
AB  - BACKGROUND: Failure in the regulation of homeostatic water balance in the brain
      is associated with severe cerebral edema and increased brain weights and may also
      play an important role in the pathogenesis of sudden infant death syndrome
      (SIDS). We genotyped three single-nucleotide polymorphisms in the aquaporin-4
      water channel-encoding gene (AQP4), which were previously shown to be associated
      with (i) SIDS in Norwegian infants (rs2075575), (ii) severe brain edema
      (rs9951307), and (iii) increased brain water permeability (rs3906956). We also
      determined whether the brain/body weight ratio is increased in SIDS infants
      compared with sex- and age-matched controls. METHODS: Genotyping of the three
      AQP4 single-nucleotide polymorphisms was performed in 160 Caucasian SIDS infants
      and 181 healthy Swiss adults using a single-base extension method. Brain and body
      weights were measured during autopsy in 157 SIDS and 59 non-SIDS infants.
      RESULTS: No differences were detected in the allelic frequencies of the three
      AQP4 single-nucleotide polymorphisms between SIDS and adult controls. The
      brain/body weight ratio was similarly distributed in SIDS and non-SIDS infants.
      CONCLUSION: Variations in the AQP4 gene seem of limited significance as
      predisposing factors in Caucasian SIDS infants. Increased brain weights may only
      become evident in conjunction with environmental or other genetic risk factors.

PMID- 24727947
TI  - Maternal tobacco smoke increased visceral adiposity and serum corticosterone
      levels in adult male rat offspring.
AB  - BACKGROUND: Maternal tobacco smoke (MTS) predisposes human and rat offspring to
      visceral obesity in early adulthood. Glucocorticoid excess also causes visceral
      obesity. We hypothesized that in utero MTS would increase visceral adiposity and
      alter the glucocorticoid pathway in young adult rats. METHODS: We developed a
      novel model of in utero MTS exposure in pregnant rats by exposing them to
      cigarette smoke from E11.5 to term. Neonatal rats were cross-fostered to control
      dams and weaned to standard rat chow through young adulthood (postnatal day 60).
      RESULTS: We demonstrated increased visceral adiposity (193%)*, increased visceral
      adipose 11-beta hydroxysteroid dehydrogenase 1 mRNA (204%)*, increased serum
      corticosterone (147%)*, and no change in glucocorticoid receptor protein in adult
      male MTS rat offspring. Female rats exposed to MTS in utero demonstrated no
      change in visceral or subcutaneous adiposity, decreased serum corticosterone
      (60%)*, and decreased adipose glucocorticoid receptor protein (66%)*. *P < 0.05.
      CONCLUSION: We conclude that in utero MTS exposure increased visceral adiposity
      and altered in the glucocorticoid pathway in a sex-specific manner. We speculate
      that in utero MTS exposure programs adipose dysfunction in adult male rat
      offspring via alteration in the glucocorticoid pathway.

PMID- 24727948
TI  - High-dose IgG therapy mitigates bile duct-targeted inflammation and obstruction
      in a mouse model of biliary atresia.
AB  - BACKGROUND: A proposed etiology of biliary atresia (BA) entails a virus-induced,
      progressive immune-mediated injury of the biliary system. Intravenous Ig (IVIg)
      has demonstrated clinical benefit in several inflammatory diseases. The aim of
      this study was to determine the therapeutic effects of high-dose IgG treatment in
      the rhesus rotavirus (RRV)-induced mouse model of BA. METHODS: Newborn mice were
      infected with RRV, and jaundiced mice were given high-dose IgG or albumin
      control. Survival, histology, direct bilirubin, liver immune cell subsets, and
      cytokine production were analyzed. RESULTS: There was no difference in overall
      survival between RRV-infected groups, however high-dose IgG resulted in decreased
      bilirubin, bile duct inflammation, and increased extrahepatic bile duct patency.
      High-dose IgG decreased vascular cell adhesion molecule-1, resulting in limited
      migration of immune cells to portal tracts. High-dose IgG significantly decreased
      CD4(+) T cell production of interleukin (IL)-2, interferon (IFN)-gamma, and tumor
      necrosis factor (TNF)-alpha and CD8(+) T cell production of IFN-gamma, as well as
      increased levels of regulatory T cells. CONCLUSION: High-dose IgG therapy in
      murine BA dramatically decreased Th1 cell-mediated inflammation and biliary
      obstruction. This study lends support for consideration of IVIg clinical trials
      in infants with BA, to diminish the progressive intrahepatic bile duct injury.

PMID- 24727950
TI  - Coexistence of multiple silicene phases in silicon grown on Ag(1 1 1).
AB  - Silicene, the silicon equivalent of graphene, is attracting increasing scientific
      and technological attention in view of the exploitation of its exotic electronic
      properties. This novel material has been theoretically predicted to exist as a
      free-standing layer in a low-buckled, stable form, and can be synthesized by the
      deposition of Si on appropriate crystalline substrates. By employing low-energy
      electron diffraction and microscopy, we have studied the growth of Si on Ag(1 1
      1) and observed a rich variety of rotationally non-equivalent silicene
      structures. Our results highlight a very complex formation diagram, reflecting
      the coexistence of different and nearly degenerate silicene phases, whose
      relative abundance can be controlled by varying the Si coverage and growth
      temperature. At variance with other studies, we find that the formation of single
      phase silicene monolayers cannot be achieved on Ag(1 1 1). 

PMID- 24727949
TI  - Intrinsic disorder in the BK channel and its interactome.
AB  - The large-conductance Ca2+-activated K+ (BK) channel is broadly expressed in
      various mammalian cells and tissues such as neurons, skeletal and smooth muscles,
      exocrine cells, and sensory cells of the inner ear. Previous studies suggest that
      BK channels are promiscuous binders involved in a multitude of protein-protein
      interactions. To gain a better understanding of the potential mechanisms
      underlying BK interactions, we analyzed the abundance, distribution, and
      potential mechanisms of intrinsic disorder in 27 BK channel variants from mouse
      cochlea, 104 previously reported BK-associated proteins (BKAPS) from cytoplasmic
      and membrane/cytoskeletal regions, plus BK beta- and gamma-subunits. Disorder was
      evaluated using the MFDp algorithm, which is a consensus-based predictor that
      provides a strong and competitive predictive quality and PONDR, which can
      determine long intrinsically disordered regions (IDRs). Disorder-based binding
      sites or molecular recognition features (MoRFs) were found using MoRFpred and
      ANCHOR. BKAP functions were categorized based on Gene Ontology (GO) terms. The
      analyses revealed that the BK variants contain a number of IDRs. Intrinsic
      disorder is also common in BKAPs, of which ~ 5% are completely disordered.
      However, intrinsic disorder is very differently distributed within BK and its
      partners. Approximately 65% of the disordered segments in BK channels are long
      (IDRs) (>50 residues), whereas >60% of the disordered segments in BKAPs are short
      IDRs that range in length from 4 to 30 residues. Both alpha and gamma subunits
      showed various amounts of disorder as did hub proteins of the BK interactome. Our
      analyses suggest that intrinsic disorder is important for the function of BK and
      its BKAPs. Long IDRs in BK are engaged in protein-protein and protein-ligand
      interactions, contain multiple post-translational modification sites, and are
      subjected to alternative splicing. The disordered structure of BK and its BKAPs
      suggests one of the underlying mechanisms of their interaction.

PMID- 24727953
TI  - Is the age of eponymous diseases in rheumatology over?

PMID- 24727951
TI  - A high resolution computer tomography scoring system to predict culture-positive
      pulmonary tuberculosis in the emergency department.
AB  - This study evaluated the use of high-resolution computed tomography (HRCT) to
      predict the presence of culture-positive pulmonary tuberculosis (PTB) in adult
      patients with pulmonary lesions in the emergency department (ED). The study
      included a derivation phase and validation phase with a total of 8,245 patients
      with pulmonary disease. There were 132 patients with culture-positive PTB in the
      derivation phase and 147 patients with culture-positive PTB in the validation
      phase. Imaging evaluation of pulmonary lesions included morphology and segmental
      distribution. The post-test probability ratios between both phases in three
      prevalence areas were analyzed. In the derivation phase, a multivariate analysis
      model identified cavitation, consolidation, and clusters/nodules in right or left
      upper lobe (except anterior segment) and consolidation of the superior segment of
      the right or left lower lobe as independent positive factors for culture-positive
      PTB, while consolidation of the right or left lower lobe (except superior
      segment) were independent negative factors. An ideal cutoff point based on the
      receiver operating characteristic (ROC) curve analysis was obtained at a score of
      1. The sensitivity, specificity, positivity predictive value, and negative
      predictive value from derivation phase were 98.5% (130/132), 99.7% (3997/4008),
      92.2% (130/141), and 99.9% (3997/3999). Based on the predicted positive
      likelihood ratio value of 328.33 in derivation phase, the post-test probability
      was observed to be 91.5% in the derivation phase, 92.5% in the validation phase,
      94.5% in a high TB prevalence area, 91.0% in a moderate prevalence area, and
      76.8% in moderate-to-low prevalence area. Our model using HRCT, which is feasible
      to perform in the ED, can promptly diagnose culture-positive PTB in moderate and
      moderate-to-low prevalence areas. 

PMID- 24727952
TI  - MiR-942 mediates hepatitis C virus-induced apoptosis via regulation of ISG12a.
AB  - The interaction between hepatitis C virus (HCV) and human hepatic innate
      antiviral responses is unclear. The aim of this study was to examine how human
      hepatocytes respond to HCV infection. An infectious HCV isolate, JFH1, was used
      to infect a newly established human hepatoma cell line HLCZ01. Viral RNA or NS5A
      protein was examined by real-time PCR or immunofluorescence respectively. The
      mechanisms of HCV-induced IFN-beta and apoptosis were explored. Our data showed
      that HLCZ01 cells supported the entire HCV lifecycle and IFN-beta and interferon
      stimulated genes (ISGs) were induced in HCV-infected cells. Viral infection
      caused apoptosis of HLCZ01 cells. Silencing of RIG-I, IRF3 or TRAIL inhibited
      ISG12a expression and blocked apoptosis of viral-infected HLCZ01 cells. Knockdown
      ISG12a blocked apoptosis of viral-infected cells. MiR-942 is a candidate negative
      regulator of ISG12a predicted by bioinformatics search. Moreover, HCV infection
      decreased miR-942 expression in HLCZ01 cells and miR-942 was inversely correlated
      with ISG12a expression in both HCV-infected cells and liver biopsies. MiR-942
      forced expression in HLCZ01 cells decreased ISG12a expression and subsequently
      suppressed apoptosis triggered by HCV infection. Conversely, silencing of miR-942
      expression by anti-miR-942 increased ISG12a expression and enhanced apoptosis in
      HCV-infected cells. Induction of Noxa by HCV infection contributed to ISG12a
      mediated apoptosis. All the data indicated that innate host response is intact in
      HCV-infected hepatocytes. MiR-942 regulates HCV-induced apoptosis of human
      hepatocytes by targeting ISG12a. Our study provides a novel mechanism by which
      human hepatocytes respond to HCV infection. 

PMID- 24727954
TI  - Statutory and mandatory training for medical staff in the NHS.

PMID- 24727956
TI  - The septic obstructed kidney: a urological emergency.

PMID- 24727957
TI  - HIV and the kidney: a UK perspective.

PMID- 24727958
TI  - Finding the perfect match: the living donor paired exchange system.

PMID- 24727959
TI  - How to write a case report.

PMID- 24727960
TI  - Total hip arthroplasty consent process: current evidence for junior doctors.

PMID- 24727961
TI  - Persistent auditory hallucinations and treatment challenges.

PMID- 24727962
TI  - Allergy: a risk factor for cardiovascular diseases?

PMID- 24727963
TI  - Optimizing knee arthroscopy documentation using a new template.
AB  - INTRODUCTION: The purpose of the study was to assess the quality of documentation
      of knee arthroscopy and evaluate the implementation of a novel operative
      template. METHOD: A 34-point assessment was undertaken based on published
      national guidelines. A retrospective study of 50 operative notes of patients
      (group A) undergoing knee arthroscopy was completed. A new operative note
      template was devised to include important criteria and assessed in 49 patients
      (group B) for its efficacy in providing appropriately detailed findings. RESULTS:
      Group A was lacking the minimum essential documentation standards expected. Some
      essential criteria for arthroscopic procedures were as low as 4%. Group B showed
      a statistically significant increase (P<0.001) in documentation accuracy
      throughout the essential criteria compared to the findings in group A.
      CONCLUSIONS: The authors conclude that the use of an evidence-based operative
      template for knee arthroscopy significantly improves the quality and accuracy of
      documentation compared to conventional free-hand operative notes.

PMID- 24727964
TI  - Gerhard Domagk: a Nobel laureate pioneer of chemotherapy.

PMID- 24727965
TI  - Bladder scanner pitfalls: beware ovarian cysts.

PMID- 24727966
TI  - Overwhelming infection causing takotsubo syndrome.

PMID- 24727967
TI  - Emphysematous pyelonephritis in a diabetic patient with autosomal dominant
      polycystic kidney disease.

PMID- 24727968
TI  - 'Fluid-wise route-foolish': intravenous vs enteral fluid administration.

PMID- 24727970
TI  - Should we be undertaking routine combined spinal epidural anaesthesia for
      elective caesarean sections?

PMID- 24727972
TI  - The Positive Consequences of Pain: A Biopsychosocial Approach.
AB  - Pain is mostly thought of as a problem-as debilitating or harmful. Despite its
      unpleasantness, however, under some conditions pain can be associated with
      positive consequences. In this review, we explore these positive biological,
      psychological, and social consequences of pain. We highlight three different
      domains in which pain may be considered to have positive consequences. First,
      pain facilitates pleasure by providing an important contrast for pleasurable
      experiences, increasing sensitivity to sensory input, and facilitating self
      rewarding behavior. Second, pain augments self-regulation and enhancement by
      increasing cognitive control, reducing rumination, and demonstrating virtue.
      Third, pain promotes affiliation by arousing empathy from others, motivating
      social connection, and enhancing group formation. Drawing on evidence scattered
      across a range of academic fields, we provide for reflection on how pain is
      represented, generate insights into pain-seeking behavior, and draw attention to
      the role of painful experiences in maximizing positive outcomes.

PMID- 24727971
TI  - Cerebral activity to opposite-sex voices reflected by event-related potentials.
AB  - Human voice is a gender discriminating cue and is important to mate selection.
      This study employed electrophysiological recordings to examine whether there is
      specific cerebral activity when presented with opposite-sex voices as compared to
      same-sex voices. Male voices and female voices were pseudo-randomly presented to
      male and female participants. In Experiment 1, participants were instructed to
      determine the gender of each voice. A late positivity (LP) response around 750 ms
      after voice onset was elicited by opposite-sex voices, as reflected by a positive
      deflection of the ERP to opposite-sex voices than that to same-sex voices. This
      LP response was prominent around parieto-occipital recording sites, and it
      suggests an opposite-sex specific process, which may reflect emotion- and/or
      reward-related cerebral activity. In Experiment 2, participants were instructed
      to press a key when hearing a non-voice pure tone and not give any response when
      they heard voice stimuli. In this task, no difference were found between the ERP
      to same-sex voices and that to opposite-sex voices, suggesting that the cerebral
      activity to opposite-sex voices may disappear without gender-related attention.
      These results provide significant implications on cognitive mechanisms with
      regard to opposite-sex specific voice processing. 

PMID- 24727973
TI  - Evil acts and malicious gossip: a multiagent model of the effects of gossip in
      socially distributed person perception.
AB  - Although person perception is central to virtually all human social behavior, it
      is ordinarily studied in isolated individual perceivers. Conceptualizing it as a
      socially distributed process opens up a variety of novel issues, which have been
      addressed in scattered literatures mostly outside of social psychology. This
      article examines some of these issues using a series of multiagent models.
      Perceivers can use gossip (information from others about social targets) to
      improve their ability to detect targets who perform rare negative behaviors. The
      model suggests that they can simultaneously protect themselves against being
      influenced by malicious gossip intended to defame specific targets. They can
      balance these potentially conflicting goals by using specific strategies
      including disregarding gossip that differs from a personally obtained impression.
      Multiagent modeling demonstrates the outcomes produced by different combinations
      of assumptions about gossip, and suggests directions for further research and
      theoretical development. 

PMID- 24727974
TI  - Depression and Social Identity: An Integrative Review.
AB  - Social relationships play a key role in depression. This is apparent in its
      etiology, symptomatology, and effective treatment. However, there has been little
      consensus about the best way to conceptualize the link between depression and
      social relationships. Furthermore, the extensive social-psychological literature
      on the nature of social relationships, and in particular, research on social
      identity, has not been integrated with depression research. This review presents
      evidence that social connectedness is key to understanding the development and
      resolution of clinical depression. The social identity approach is then used as a
      basis for conceptualizing the role of social relationships in depression,
      operationalized in terms of six central hypotheses. Research relevant to these
      hypotheses is then reviewed. Finally, we present an agenda for future research to
      advance theoretical and empirical understanding of the link between social
      identity and depression, and to translate the insights of this approach into
      clinical practice.

PMID- 24727975
TI  - Changes in adult attachment styles in American college students over time: a meta
      analysis.
AB  - The current article examines changes over time in a commonly used measure of
      adult attachment style. A cross-temporal meta-analysis was conducted on 94
      samples of American college students (total N = 25,243, between 1988 and 2011)
      who chose the most representative description of four possible attachment styles
      (Secure, Dismissing, Preoccupied, and Fearful) on the Relationship Questionnaire.
      The percentage of students with Secure attachment styles has decreased in recent
      years (1988: 48.98%; 2011: 41.62%), whereas the percentage of students with
      Insecure attachment styles (sum of Dismissing, Preoccupied, Fearful) has
      increased in recent years (1988: 51.02%; 2011: 58.38%). The percentage of
      students with Dismissing attachment styles has increased over time (1988: 11.93%;
      2011: 18.62%), even after controlling for age, gender, race, and publication
      status. Positive views of others have declined across the same time period. We
      discuss possible implications and explanations for these changes. 

PMID- 24727976
TI  - Particle aggregation mechanisms in ionic liquids.
AB  - Aggregation of sub-micron and nano-sized polystyrene latex particles was studied
      in room temperature ionic liquids (ILs) and in their water mixtures by time
      resolved light scattering. The aggregation rates were found to vary with the IL
      to-water molar ratio in a systematic way. At the water side, the aggregation rate
      is initially small, but increases rapidly with increasing IL content, and reaches
      a plateau value. This behaviour resembles simple salts, and can be rationalized
      by the competition of double-layer and van der Waals forces as surmised by the
      classical theory of Derjaguin, Landau, Verwey, and Overbeek (DLVO). At the IL
      side, aggregation slows down again. Two generic mechanisms could be identified to
      be responsible for the stabilization in ILs, namely viscous stabilization and
      solvation stabilization. Viscous stabilization is important in highly viscous
      ILs, as it originates from the slowdown of the diffusion controlled aggregation
      due to the hindrance of the diffusion in a viscous liquid. The solvation
      stabilization mechanism is system specific, but can lead to a dramatic slowdown
      of the aggregation rate in ILs. This mechanism is related to repulsive solvation
      forces that are operational in ILs due to the layering of the ILs close to the
      surfaces. These two stabilization mechanisms are suspected to be generic, as they
      both occur in different ILs, and for particles differing in surface
      functionalities and size. 

PMID- 24727977
TI  - Jellyfish as prey: frequency of predation and selective foraging of Boops boops
      (Vertebrata, Actinopterygii) on the mauve stinger Pelagia noctiluca (Cnidaria,
      Scyphozoa).
AB  - In recent years, jellyfish blooms have attracted considerable scientific interest
      for their potential impacts on human activities and ecosystem functioning, with
      much attention paid to jellyfish as predators and to gelatinous biomass as a
      carbon sink. Other than qualitative data and observations, few studies have
      quantified direct predation of fish on jellyfish to clarify whether they may
      represent a seasonally abundant food source. Here we estimate predation frequency
      by the commercially valuable Mediterranean bogue, Boops boops on the mauve
      stinger jellyfish, Pelagia noctiluca, in the Strait of Messina (NE Sicily). A
      total of 1054 jellyfish were sampled throughout one year to quantify predation by
      B. boops from bite marks on partially eaten jellyfish and energy density of the
      jellyfish. Predation by B. boops in summer was almost twice that in winter, and
      they selectively fed according to medusa gender and body part. Calorimetric
      analysis and biochemical composition showed that female jellyfish gonads had
      significantly higher energy content than male gonads due to more lipids and that
      gonads had six-fold higher energy content than the somatic tissues due to higher
      lipid and protein concentrations. Energetically, jellyfish gonads represent a
      highly rewarding food source, largely available to B. boops throughout spring and
      summer. During the remainder of the year, when gonads were not very evident, fish
      predation switched towards less-selective foraging on the somatic gelatinous
      biomass. P. noctiluca, the most abundant jellyfish species in the Mediterranean
      Sea and a key planktonic predator, may represent not only a nuisance for human
      leisure activities and a source of mortality for fish eggs and larvae, but also
      an important resource for fish species of commercial value, such as B. boops. 

PMID- 24727979
TI  - A masked diboron in Cu-catalysed borylation reaction: highly regioselective
      formal hydroboration of alkynes for synthesis of branched alkenylborons.
AB  - The use of a masked diboron as a boron source in the presence of a Cu-N
      heterocyclic carbene (NHC) catalyst enables alkyl-, aryl-, heteroatom- and silyl
      substituted terminal alkynes to undergo alpha-selective formal hydroboration to
      give diverse branched alkenylboron compounds exclusively. Synthetic potential of
      this alpha-selective hydroboration has been demonstrated by total synthesis of
      pharmaceutically significant bexarotene and LG100268. 

PMID- 24727978
TI  - A cannabigerol derivative suppresses immune responses and protects mice from
      experimental autoimmune encephalomyelitis.
AB  - Phytocannabinoids that do not produce psychotropic effects are considered of
      special interest as novel therapeutic agents in CNS diseases. A cannabigerol
      quinone, the compound VCE-003, has been shown to alleviate symptoms in a viral
      model of multiple sclerosis (MS). Hence, we studied T cells and macrophages as
      targets for VCE-003 and its efficacy in an autoimmune model of MS. Proliferation,
      cell cycle, expression of activation markers was assessed by FACs in human
      primary T cells, and cytokine and chemokine production was evaluated.
      Transcription was studied in Jurkat cells and RAW264.7 cells were used to study
      the effects of VCE-003 on IL-17-induced macrophage polarization to a M1
      phenotype. Experimental autoimmune encephalomyelitis (EAE) was induced by myelin
      oligodendrocyte glycoprotein (MOG35-55) immunization and spinal cord pathology
      was assessed by immunohistochemistry. Neurological impairment was evaluated using
      disease scores. We show here that VCE-003 inhibits CD3/CD28-induced
      proliferation, cell cycle progression and the expression of the IL-2Ralpha and
      ICAM-1 activation markers in human primary T cells. VCE-003 inhibits the
      secretion of Th1/Th17 cytokines and chemokines in primary murine T cells, and it
      reduces the transcriptional activity of the IL-2, IL-17 and TNFalpha promoters
      induced by CD3/CD28. In addition, VCE-003 and JWH-133, a selective CB2 agonist,
      dampened the IL-17-induced polarization of macrophages to a pro-inflammatory M1
      profile. VCE-003 also prevented LPS-induced iNOS expression in microglia. VCE-003
      ameliorates the neurological defects and the severity of MOG-induced EAE in mice
      through CB2 and PPARgamma receptor activation. A reduction in cell infiltrates,
      mainly CD4+ T cells, was observed, and Th1 and Th17 responses were inhibited in
      the spinal cord of VCE-003-treated mice, accompanied by weaker microglial
      activation, structural preservation of myelin sheets and reduced axonal damage.
      This study highlights the therapeutic potential of VCE-003 as an agent for the
      treatment of human immune diseases with both inflammatory and autoimmune
      components.

PMID- 24727980
TI  - A pictorial schema for a comprehensive user-oriented identification of medical
      Apps.
AB  - OBJECTIVES: The huge amount of released medical apps prevents medical app users
      from believing that medical scientific societies and other accreditation bodies
      as well, have the resources and the power for assigning to any medical app a
      quality score. By the time being, any medical app user has to take the risks
      related to the frequently insufficient accreditation of that app. Providing clear
      user-oriented schemas, to be adopted both when putting a medical App on the
      market and when an App comes to be evaluated by a cohort or single users, becomes
      crucial. The aim of our research was to define a pictorial identification one
      shot schema for a comprehensive user-oriented identification of medical apps.
      METHODS: Adopting a pictorial approach is common in software design modeling. To
      build up our identification schema we started from the limited number of Apps
      already available on a web site of app reviews (iMedicalApps.com), and we
      identified an appropriately large set of attributes for describing medical apps.
      We arranged the attributes in six main families. We organized them in a one-shot
      comprehensive pictorial schema. We adopted a traffic light color code for
      assessing each attribute, that was sufficient to provide simple elements of
      alerts and alarms regarding a single App. Then, we considered apps from
      iMedicalApps.com web site belonging to three medical specialties: cardiology,
      oncology, and pharma and analyzed them according to the proposed pictorial
      schema. RESULTS: A pictorial schema having the attributes grouped in the families
      related to "Responsible Promoters", "Offered Services", "Searching Methods",
      "Applications Domains", "Envisaged Users", and "Qualifiers and Quantifiers" has
      been identified. Furthermore, we produced a one-shot pictorial schema for each
      considered app, and for each medical specialty, we produced it also in an
      aggregated form. CONCLUSIONS: The one-shot pictorial schema provides a useful
      perception of when and where to use a considered app. It fits positively the
      expectations of potential but different user's profiles. It can be a first step
      towards a systematic assessment of apps from the user viewpoint.

PMID- 24727981
TI  - Glycolytic genes are targets of the nuclear receptor Ad4BP/SF-1.
AB  - Genetic deficiencies in transcription factors can lead to the loss of certain
      types of cells and tissue. The steroidogenic tissue-specific nuclear receptor
      Ad4BP/SF-1 (NR5A1) is one such gene, because mice in which this gene is disrupted
      fail to develop the adrenal gland and gonads. However, the specific role of
      Ad4BP/SF-1 in these biological events remains unclear. Here we use chromatin
      immunoprecipitation sequencing to show that nearly all genes in the glycolytic
      pathway are regulated by Ad4BP/SF-1. Suppression of Ad4BP/SF-1 by small
      interfering RNA reduces production of the energy carriers ATP and nicotinamide
      adenine dinucleotide phosphate, as well as lowers expression of genes involved in
      glucose metabolism. Together, these observations may explain tissue dysgenesis as
      a result of Ad4BP/SF-1 gene disruption in vivo. Considering the function of
      estrogen-related receptor alpha, the present study raises the possibility that
      certain types of nuclear receptors regulate sets of genes involved in metabolic
      pathways to generate energy carriers. 

PMID- 24727983
TI  - Targeting oncogenic drivers.
AB  - Cancer is a genetic disease caused by a series of somatic and/or germline
      mutations. The roles of oncogenes and tumor suppressors in cancer molecular
      origin have been well established. Targeting oncogene products has become an
      attractive therapeutic strategy with great clinical success, whereas tumor
      suppressors are considered 'undruggable' because current technology is not able
      to restore tumor suppressor function in metastatic disease. Although systematic
      approaches to discover genetic alterations have become available to individual
      patients, differentiating driver from passenger mutations and identifying and
      validating drug targets remain challenging. Protein tyrosine kinases play crucial
      roles in virtually all cellular processes and possess structural features that
      render them 'druggable'. Monoclonal antibodies and small-molecule inhibitors
      represent two major classes of targeted therapeutic agents, each possessing its
      own strength and weakness. Although initial successes have been achieved,
      targeted therapy faces many challenges that need to be addressed and hurdles to
      overcome.

PMID- 24727982
TI  - Neuronal activity promotes oligodendrogenesis and adaptive myelination in the
      mammalian brain.
AB  - Myelination of the central nervous system requires the generation of functionally
      mature oligodendrocytes from oligodendrocyte precursor cells (OPCs). Electrically
      active neurons may influence OPC function and selectively instruct myelination of
      an active neural circuit. In this work, we use optogenetic stimulation of the
      premotor cortex in awake, behaving mice to demonstrate that neuronal activity
      elicits a mitogenic response of neural progenitor cells and OPCs, promotes
      oligodendrogenesis, and increases myelination within the deep layers of the
      premotor cortex and subcortical white matter. We further show that this neuronal
      activity-regulated oligodendrogenesis and myelination is associated with improved
      motor function of the corresponding limb. Oligodendrogenesis and myelination
      appear necessary for the observed functional improvement, as epigenetic blockade
      of oligodendrocyte differentiation and myelin changes prevents the activity
      regulated behavioral improvement. 

PMID- 24727984
TI  - Successes and limitations of targeted cancer therapy in breast cancer.
AB  - Breast cancer is not a single disease. Specific biological processes and distinct
      genetic pathways are associated with prognosis and sensitivity to chemotherapy
      and targeted agents in different subtypes of breast cancers. As a consequence,
      breast cancer can be classified by molecular events. A primary challenge for
      future drug development in breast cancer will be to distinguish genes and
      pathways that 'drive' cancer proliferation (drivers) from genes and pathways that
      have no role in the development of cancer (passengers). The identification of
      functional pathways that are enriched for mutated genes will select subpopulation
      of patients likely to be sensitive to biology-driven targeted agents. The
      selection of driver pathways in resistant tumors will permit to discover a
      biology-driven platform for new drug development to overcome resistance. We are
      moving in the era of stratified and personalized therapy. Personalized cancer
      therapy is based on the precept that detailed molecular characterization of the
      patient's tumor and its microenvironment will enable tailored therapies to
      improve outcomes and decrease toxicity. However, there are numerous challenges we
      need to overcome before delivering on the promise of personalized cancer therapy.
      These include tumor heterogeneity and molecular evolution, costs and potential
      morbidity of biopsies, lack of effective drugs against most genomic aberrations,
      technical limitations of molecular tests, and reimbursement and regulatory
      hurdles. Critically, successes and limitations surrounding personalized cancer
      therapy must be tempered with realistic expectations, which, today, encompass
      increased survival times for only a portion of patients.

PMID- 24727985
TI  - Successes and limitations of targeted cancer therapy in colon cancer.
AB  - Constant development of chemotherapy and more recently the introduction of VEGF-
      and epidermal growth factor receptor (EGFR)-directed agents have improved
      significantly the treatment of patients with colorectal cancer. In the adjuvant
      setting, especially for UICC stage III colon cancer patients, fluoropyrimidine in
      combination with oxaliplatin is usually the standard of care. With some surprise,
      both VEGF inhibitors (for all patients) and EGFR (for patients with KRAS exon 2
      mutant tumors) have failed to improve adjuvant chemotherapy. Also, adding an EGFR
      antibody to FOLFOX as perioperative treatment in patients with resectable exon 2
      KRAS wild-type liver metastases was not successful. However, patients with
      metastatic disease harboring a RAS wild-type tumor are with no doubt candidates
      for combination chemotherapy plus an EGFR antibody. In patients with liver
      limited disease, metastases may become resectable following intensive
      chemotherapy (including an EGFR antibody for RAS wild-type disease), which may
      result in cure or significantly prolonged survival. In the case of RAS wild-type
      tumors, median survival in patients with unresectable metastases approaches now 3
      years if EGFR antibodies are used in the first line. There is little evidence for
      VEGF inhibitors in patients with RAS wild-type or mutant disease in first-line
      chemotherapy if combination chemotherapy is considered. VEGF inhibitors, however,
      are very potent drugs to be combined with chemotherapy for second-line treatment.

PMID- 24727986
TI  - Successes and limitations of targeted cancer therapy in gastrointestinal stromal
      tumors.
AB  - In gastrointestinal stromal tumors (GIST), molecularly targeted therapies,
      starting with imatinib, are directed against an activating mutation of KIT or
      PDGFRA, which drives the disease. Their efficacy has brought the median survival
      from one to at least 5 years in the metastatic setting. Tumor response patterns
      may include tumor shrinkage or not, but are marked by pathologic and radiological
      changes in tumor tissue. Tumor sensitivity to imatinib can be precisely predicted
      by the mutational status. However, the metastatic disease has not been truly
      converted into a chronic condition since secondary resistance to imatinib remains
      a major limiting factor occurring after a median of 2 years at least in most
      patients. Further-line therapies are available, i.e. with sunitinib and
      regorafenib, which can prolong progression-free survival for limited time
      intervals. Resistance is due to secondary mutations. These give rise to a
      molecular heterogeneity, which represents a formidable therapeutic challenge.
      However, the scenario has aspects of a 'liquid resistance'. In fact, resistance
      may spread in a stepwise fashion throughout the tumor: focal progression may be
      one possible clinical presentation, and tyrosine kinase inhibitors may impact
      tumor growth even beyond conventional progression. In addition, sensitive and
      resistant clones may expand and shrink depending on the selective pressure of
      tyrosine kinase inhibitors, with be possible responses on rechallenge with drugs.
      In the adjuvant treatment of high-risk molecularly sensitive GIST, imatinib is
      able to substantially delay relapses, if due to occur, with a limited survival
      benefit, though, apparently, without impacting the cure rate.

PMID- 24727987
TI  - Successes and limitations of targeted cancer therapy in lung cancer.
AB  - Human cancers usually evolve through multistep processes. These processes are
      driven by the accumulation of abundant genetic and epigenetic abnormalities.
      However, some lung cancers depend on a single activated oncogene by somatic
      mutation, termed 'driver oncogenic mutations', for their proliferation and
      survival. EGFR(epidermal growth factor receptor) mutations and ALK(anaplastic
      lymphoma kinase) rearrangement are typical examples of such driver oncogenic
      mutations found in lung adenocarcinomas. EGFR-tyrosine kinase inhibitors (TKIs)
      or ALK-TKIs significantly improved treatment outcomes compared with conventional
      cytotoxic chemotherapy in patients with lung cancers harboring EGFR mutations or
      ALK rearrangement, respectively. Therefore, treatment strategies for lung cancers
      have dramatically changed from a 'general and empiric' to a 'personalized and
      evidence-based' approach according to the driver oncogenic mutation. Several
      novel driver oncogenic mutations, which are candidates as novel targets, such as
      ERBB2, BRAF, ROS1, and RET, have been discovered. Despite these successes,
      several limitations have arisen. One example is that some lung cancers do not
      respond to treatments targeting driver oncogenic mutations, as exemplified in
      KRAS-mutated lung cancers. Another is resistance to molecular-targeted drugs.
      Such resistance includes de novo resistance and acquired resistance. A number of
      molecular mechanisms underlying such resistance have been reported. These
      mechanisms can be roughly divided into three categories: alteration of the
      targeted oncogenes themselves by secondary mutations or amplification, activation
      of an alternative oncogenic signaling track, and conversion of cellular
      characteristics. Overcoming resistance is a current area of urgent clinical
      research.

PMID- 24727988
TI  - Successes and limitations of targeted cancer therapy in melanoma.
AB  - The treatment of stage IV melanoma has witnessed a very impressive pace of
      innovation in recent years, to a point where the management of these patients has
      very little in common to what was standard practice 5 years ago. If the gain in
      overall survival, the high response rates or the induction of a significant
      fraction of long survivors are all very exciting news for our patients and their
      families, the path that led to these discoveries is as important. Rather than
      empirical, the development of these new strategies has been extremely rational,
      based on state-of-the-art basic biology and immunology, exemplary translational
      research and, finally, hypothesis-driven targeted trials that led to rapid
      approval. In this review, we will cover all the new targeted therapies that have
      emerged as the results of these translational programs, focusing mainly on
      signaling pathway- and immune checkpoint-targeted therapies. Taken collectively,
      these new developments set the bar for a new paradigm in future translational and
      clinical research in both melanoma as well as other tumor types.

PMID- 24727989
TI  - Successes and limitations of targeted cancer therapy in ovarian cancer.
AB  - In ovarian cancer, the clinical development of anticancer agents targeting DNA
      repair has been associated with significant results because of the elucidation of
      the different types of damages and repair systems, including PARP. The discovery
      of the BRCA mutation and its role in ovarian cancer and the clinical application
      of the concept of synthetic lethality have been the rationale for the successful
      testing of PARP inhibitors in BRCA mutated ovarian cancer patients. The recent
      knowledge of the molecular features of low grade ovarian cancer and the
      application of the concept of synthetic lethality also in this well-defined
      pathological entity have prompted the clinical evaluation of a combination of
      PI3K/MEK inhibitors, the first results of which have been already reported.

PMID- 24727990
TI  - Successes and limitations of targeted therapies in renal cell carcinoma.
AB  - Until recently, the standard treatment for metastatic renal cell carcinoma (RCC)
      was nonspecific immunotherapy based on interleukin-2 or interferon-alpha. This
      was associated with a modest survival benefit and with significant clinical
      toxicities. The understanding of numerous molecular pathways in RCC, including
      HIF, VEGF, mTOR, and the consecutive use of targeted therapies since the
      beginning of 2005 have significantly improved outcomes for patients with
      metastatic RCC with an overall survival greater than 2 years. At present, at
      least 7 targeted agents are approved for first and consecutive lines of treatment
      of clear cell metastatic RCC. Long-term benefit and extended survival may be
      achieved through the optimal use of targeted therapies: optimal dosing, adverse
      event management and treatment duration and compliance. Advances in the finding
      of prognostic factors highlight the potential for personalizing treatment for
      patients with metastatic RCC. Data regarding the best sequencing of targeted
      therapies, predictive biomarkers, best timing of surgery, patient risk profiles,
      understanding of resistance mechanisms and safety of targeted therapies are
      growing and will provide a further step ahead in the management of advanced RCC.
      In parallel, a new class of therapeutics is emerging in RCC: immunotherapy; in
      particular check-point blockade antibodies are showing very promising results.

PMID- 24727991
TI  - Effect of Si doping on the electronic properties of BN monolayer.
AB  - The effect of Si doping on the stability, electronic structure, and electron
      transport properties of boron nitride (BN) monolayer has been investigated by
      density functional theory method. Unique features in the electron transport
      characteristics consisting of a significant enhancement of current at the Si
      site, diode-like asymmetric current-voltage response, and negative differential
      resistance are noted for the doped BN monolayer. These features are found to
      result from new "tunnel" channels induced by the substitutional Si atom near
      Fermi level in the band gap. The calculated position-projected tunneling currents
      providing scanning tunneling micrograph clearly discern the site-dependence of
      the Si atom and can be used to distinguish substitutional sites of atomic dopants
      in the monolayer. 

PMID- 24727992
TI  - [First-line therapy of advanced or metastasized renal cell carcinoma: phase III,
      open, randomized sequence study to examine efficacy and tolerance of sorafenib
      followed by pazopanib versus pazopanib followed by sorafenib in the first-line
      treatment of patients with advanced or metastasized renal cell carcinoma (SWITCH
      2 - AN 33/11)].

PMID- 24727993
TI  - [Regional for residents: German Society of Residents in Urology programs at
      regional urology congresses].

PMID- 24727994
TI  - [Uretero(reno)scopy: management of complications].
AB  - Rigid and flexible uretero(reno)scopy (URS) are safe and effective methods in
      interventional calculus therapy. Complications are rare and can be avoided in
      advance in many cases. In ureteroliths, URS has in many cases replaced
      extracorporeal shock wave lithotripsy (ESWL) as the method of first choice.
      However, it is important to describe in detail the advantages and disadvantages
      as well as the risks of the procedure to the patient. 

PMID- 24727995
TI  - Cytotoxic response of human regulatory T cells upon T-cell receptor-mediated
      activation: a matter of purity.

PMID- 24727997
TI  - Non-replicating rhabdovirus-derived particles (NRRPs) eradicate acute leukemia by
      direct cytolysis and induction of antitumor immunity.

PMID- 24727996
TI  - The evolution of clinical trials for infant acute lymphoblastic leukemia.
AB  - Acute lymphoblastic leukemia (ALL) in infants has a significantly inferior
      outcome in comparison with older children. Despite initial improvements in
      survival of infants with ALL since establishment of the first pediatric
      cooperative group ALL trials, the poor outcome has plateaued in recent years.
      Historically, infants were treated on risk-adapted childhood ALL protocols. These
      studies were pivotal in identifying the need for infant-specific protocols,
      delineating prognostic categories and the requirement for a more unified approach
      between study groups to overcome limitations in accrual because of low incidence.
      This subsequently led to the development of collaborative infant-specific
      studies. Landmark outcomes have included the elimination of cranial radiotherapy
      following the discovery of intrathecal and high-dose systemic therapy as a
      superior and effective treatment strategy for central nervous system disease
      prophylaxis, with improved neurodevelopmental outcome. Universal prospective
      identification of independent adverse prognostic factors, including presence of a
      mixed lineage leukemia rearrangement and young age, has established the basis for
      risk stratification within current trials. The infant-specific trials have
      defined limits to which conventional chemotherapeutic agents can be intensified
      to optimize the balance between treatment efficacy and toxicity. Despite
      variations in therapeutic intensity, there has been no recent improvement in
      survival due to the equilibrium between relapse and toxicity. Ultimately, to
      improve the outcome for infants with ALL, key areas still to be addressed include
      identification and adaptation of novel prognostic markers and innovative
      therapies, establishing the role of hematopoietic stem cell transplantation in
      first complete remission, treatment strategies for relapsed/refractory disease
      and monitoring and timely intervention of late effects in survivors. This would
      be best achieved through a single unified international trial. 

PMID- 24727998
TI  - Vorinostat in combination with lenalidomide and dexamethasone in patients with
      relapsed or refractory multiple myeloma.

PMID- 24727999
TI  - Separating bedtime rest from activity using waist or wrist-worn accelerometers in
      youth.
AB  - Recent interest in sedentary behavior and technological advances expanded use of
      watch-size accelerometers for continuous monitoring of physical activity (PA)
      over extended periods (e.g., 24 h/day for 1 week) in studies conducted in natural
      living environment. This approach necessitates the development of new methods
      separating bedtime rest and activity periods from the accelerometer recordings.
      The goal of this study was to develop a decision tree with acceptable accuracy
      for separating bedtime rest from activity in youth using accelerometer placed on
      waist or wrist. Minute-by-minute accelerometry data were collected from 81 youth
      (10-18 years old, 47 females) during a monitored 24-h stay in a whole-room
      indirect calorimeter equipped with a force platform covering the floor to detect
      movement. Receiver Operating Characteristic (ROC) curve analysis was used to
      determine the accelerometer cut points for rest and activity. To examine the
      classification differences, the accelerometer bedtime rest and activity
      classified by the algorithm in the development group (n = 41) were compared with
      actual bedtime rest and activity classification obtained from the room
      calorimeter-measured metabolic rate and movement data. The selected optimal
      bedtime rest cut points were 20 and 250 counts/min for the waist- and the wrist
      worn accelerometer, respectively. The selected optimal activity cut points were
      500 and 3,000 counts/min for waist and wrist-worn accelerometers, respectively.
      Bedtime rest and activity were correctly classified by the algorithm in the
      validation group (n = 40) by both waist- (sensitivity: 0.983, specificity: 0.946,
      area under ROC curve: 0. 872) and wrist-worn (0.999, 0.980 and 0.943)
      accelerometers. The decision tree classified bedtime rest correctly with higher
      accuracy than commonly used automated algorithm for both waist- and wrist-warn
      accelerometer (all p<0.001). We concluded that cut points developed and validated
      for waist- and wrist-worn uniaxial accelerometer have a good power for accurate
      separation of time spent in bedtime rest from activity in youth. 

PMID- 24728000
TI  - Simulating of the measurement-device independent quantum key distribution with
      phase randomized general sources.
AB  - We present a model on the simulation of the measurement-device independent
      quantum key distribution (MDI-QKD) with phase randomized general sources. It can
      be used to predict experimental observations of a MDI-QKD with linear channel
      loss, simulating corresponding values for the gains, the error rates in different
      basis, and also the final key rates. Our model can be applicable to the MDI-QKDs
      with arbitrary probabilistic mixture of different photon states or using any
      coding schemes. Therefore, it is useful in characterizing and evaluating the
      performance of the MDI-QKD protocol, making it a valuable tool in studying the
      quantum key distributions. 

PMID- 24728001
TI  - Nonmetallic substrates for growth of silicene: an ab initio prediction.
AB  - By means of first-principles calculations we predict the stability of silicene
      layers as buckled honeycomb lattices on Cl-passivated Si(1 1 1) and clean CaF2(1
      1 1) surfaces. The van der Waals interaction between silicene and the inert
      substrate stabilizes the adsorbate system while not destroying the Si pz-derived
      linear bands forming Dirac cones at the Brillouin zone corners. Only small gaps
      of about 3 and 52 meV are opened. 

PMID- 24728002
TI  - Label-free identification and characterization of murine hair follicle stem cells
      located in thin tissue sections with Raman micro-spectroscopy.
AB  - Stem cells offer tremendous opportunities for regenerative medicine. Over the
      past decade considerable research has taken place to identify and characterize
      the differentiation states of stem cells in culture. Raman micro-spectroscopy has
      emerged as an ideal technology since it is fast, nondestructive, and does not
      require potentially toxic dyes. Raman spectroscopy systems can also be
      incorporated into confocal microscope imaging systems allowing spectra to be
      obtained from below the tissue surface. Thus there is significant potential for
      monitoring stem cells in living tissue. Stem cells that reside in hair follicles
      are suitable for testing this possibility since they are close to the skin
      surface, and typically clustered around the bulge area. One of the first steps
      needed would be to obtain Raman micro-spectra from stem cells located in thin
      sections of tissue, and then see whether these spectra are clearly different from
      those of the surrounding differentiated cells. To facilitate this test, standard
      5 MUm thick sections of murine skin tissue were stained to identify the location
      of hair follicle stem cells and their progeny. Raman spectra were then obtained
      from adjacent cells in a subsequent unstained 10 MUm thick section. The spectra
      revealed significant differences in peak intensities associated with nucleic
      acids, proteins, lipids and amino acids. Statistical analyses of the Raman micro
      spectra identified stem cells with 98% sensitivity and 94% specificity, as
      compared with a CD34 immunostaining gold standard. Furthermore analyses of the
      spectral variance indicated differences in cellular dynamics between the two cell
      groups. This study shows that Raman micro-spectroscopy has a potential role in
      identifying adult follicle stem cells, laying the groundwork for future
      applications of hair follicle stem cells and other somatic stem cells in situ. 

PMID- 24728003
TI  - Assessing trait covariation and morphological integration on phylogenies using
      evolutionary covariance matrices.
AB  - Morphological integration describes the degree to which sets of organismal traits
      covary with one another. Morphological covariation may be evaluated at various
      levels of biological organization, but when characterizing such patterns across
      species at the macroevolutionary level, phylogeny must be taken into account. We
      outline an analytical procedure based on the evolutionary covariance matrix that
      allows species-level patterns of morphological integration among structures
      defined by sets of traits to be evaluated while accounting for the phylogenetic
      relationships among taxa, providing a flexible and robust complement to related
      phylogenetic independent contrasts based approaches. Using computer simulations
      under a Brownian motion model we show that statistical tests based on the
      approach display appropriate Type I error rates and high statistical power for
      detecting known levels of integration, and these trends remain consistent for
      simulations using different numbers of species, and for simulations that differ
      in the number of trait dimensions. Thus, our procedure provides a useful means of
      testing hypotheses of morphological integration in a phylogenetic context. We
      illustrate the utility of this approach by evaluating evolutionary patterns of
      morphological integration in head shape for a lineage of Plethodon salamanders,
      and find significant integration between cranial shape and mandible shape.
      Finally, computer code written in R for implementing the procedure is provided. 

PMID- 24728005
TI  - Amplicon-based metagenomic analysis of mixed fungal samples using proton release
      amplicon sequencing.
AB  - Next generation sequencing technology has revolutionised microbiology by allowing
      concurrent analysis of whole microbial communities. Here we developed and
      verified similar methods for the analysis of fungal communities using a proton
      release sequencing platform with the ability to sequence reads of up to 400 bp in
      length at significant depth. This read length permits the sequencing of amplicons
      from commonly used fungal identification regions and thereby taxonomic
      classification. Using the 400 bp sequencing capability, we have sequenced
      amplicons from the ITS1, ITS2 and LSU fungal regions to a depth of approximately
      700,000 raw reads per sample. Representative operational taxonomic units (OTUs)
      were chosen by the USEARCH algorithm, and identified taxonomically through
      nucleotide blast (BLASTn). Combination of this sequencing technology with the
      bioinformatics pipeline allowed species recognition in two controlled fungal
      spore populations containing members of known identity and concentration. Each
      species included within the two controlled populations was found to correspond to
      a representative OTU, and these OTUs were found to be highly accurate
      representations of true biological sequences. However, the absolute number of
      reads attributed to each OTU differed among species. The majority of species were
      represented by an OTU derived from all three genomic regions although in some
      cases, species were only represented in two of the regions due to the absence of
      conserved primer binding sites or due to sequence composition. It is apparent
      from our data that proton release sequencing technologies can deliver a
      qualitative assessment of the fungal members comprising a sample. The fact that
      some fungi cannot be amplified by specific "conserved" primer pairs confirms our
      recommendation that a multi-region approach be taken for other amplicon-based
      metagenomic studies. 

PMID- 24728004
TI  - Histone deacetylase inhibitors sensitize lung cancer cells to hyperthermia:
      involvement of Ku70/SirT-1 in thermo-protection.
AB  - This study describes the sensitization mechanism to thermal stress by histone
      deacetylase inhibitors (HDACIs) in lung cancer cells and shows that Ku70, based
      on its acetylation status, mediates the protection of lung cancer from
      hyperthermia (42.5 degrees C, 1-6 hrs). Ku70 regulates apoptosis by sequestering
      pro-apoptotic Bax. However, its role in thermal stress is not fully understood.
      The findings showed that, pre-treating lung cancer cells with HDACIs,
      nicotinamide (NM) or Trichostatin A (TsA) or both significantly enhanced
      hyperthermia-induced Bax-dependent apoptosis in PC-10 cells. We found that
      hyperthermia induces SirT-1, Sirtuin, upregulation but not HDAC6 or SirT-3,
      therefore transfection with dominant negative SirT-1 (Y/H) also eliminated the
      protection and resulted in more cell death by hyperthermia, in H1299 cells
      through Bax activation. Hyperthermia alone primed lung cancer cells to apoptosis
      without prominent death. After hyperthermia Bax was upregulated, Bcl-2 was
      downregulated, the Bax/Bcl-2 ratio was inversed and Bax/Bcl-2 heterodimer was
      dissociated. Although hyperthermia did not affect total Ku70 expression level, it
      stimulated Ku70 deacetylation, which in turn could bind more Bax in the PC-10
      cells. These findings suggest an escape mechanism from hyperthermia-induced Bax
      activation. To verify the role of Ku70 in this protection mechanism, Ku70 was
      silenced by siRNA. Ku70 silencing significantly sensitized the lung cancer cells
      to hyperthermia. The Ku70 KD cells underwent cytotoxic G1 arrest and caspase
      dependant apoptosis when compared to scrambled transfectants which showed only
      G2/M cytostatic arrest in the cell lines investigated, suggesting an additional
      cell cycle-dependent, novel, role of Ku70 in protection from hyperthermia. Taken
      together, our data show a Ku70-dependent protection mechanism from hyperthermia.
      Targeting Ku70 and/or its acetylation during hyperthermia may represent a
      promising therapeutic approach for lung cancer. 

PMID- 24728006
TI  - Self-powered ultraviolet photodetectors based on selectively grown ZnO nanowire
      arrays with thermal tuning performance.
AB  - A self-powered Schottky-type ultraviolet photodetector with Al-Pt interdigitated
      electrodes has been fabricated based on selectively grown ZnO nanowire arrays. At
      zero bias, the fabricated photodetector exhibited high sensitivity and excellent
      selectivity to UV light illumination with a fast response time of 81 ms. By
      tuning the Schottky barrier height through the thermally induced variation of the
      interface chemisorbed oxygen, an ultrahigh sensitivity of 3.1 * 10(4) was
      achieved at 340 K without an external power source, which was 82% higher than
      that obtained at room temperature. According to the thermionic emission-diffusion
      theory and the solar cell theory, the changes in the photocurrent of the
      photodetector at zero bias with various system temperatures were calculated,
      which agreed well with the experimental data. This work demonstrates a promising
      approach to modulating the performance of a self-powered photodetector by heating
      and provides theoretical support for studying the thermal effect on the future
      photoelectric device. 

PMID- 24728007
TI  - Identification of a novel G2073A mutation in 23S rRNA in amphenicol-selected
      mutants of Campylobacter jejuni.
AB  - OBJECTIVES: This study was conducted to examine the development and molecular
      mechanisms of amphenicol resistance in Campylobacter jejuni by using in vitro
      selection with chloramphenicol and florfenicol. The impact of the resistance
      development on growth rates was also determined using in vitro culture. METHODS:
      Chloramphenicol and florfenicol were used as selection agents to perform in vitro
      stepwise selection. Mutants resistant to the selective agents were obtained from
      the selection process. The mutant strains were compared with the parent strain
      for changes in MICs and growth rates. The 23S rRNA gene and the L4 and L22
      ribosomal protein genes in the mutant strains and the parent strain were
      amplified and sequenced to identify potential resistance-associated mutations.
      RESULTS: C. jejuni strains that were highly resistant to chloramphenicol and
      florfenicol were obtained from in vitro selection. A novel G2073A mutation in all
      three copies of the 23S rRNA gene was identified in all the resistant mutants
      examined, which showed resistance to both chloramphenicol and florfenicol. In
      addition, all the mutants selected by chloramphenicol also exhibited the G74D
      modification in ribosomal protein L4, which was previously shown to confer a low
      level erythromycin resistance in Campylobacter species. The mutants selected by
      florfenicol did not have the G74D mutation in L4. Notably, the amphenicol
      resistant mutants also exhibited reduced susceptibility to erythromycin,
      suggesting that the selection resulted in cross resistance to macrolides.
      CONCLUSIONS: This study identifies a novel point mutation (G2073A) in 23S rRNA in
      amphenicol-selected mutants of C. jejuni. Development of amphenicol resistance in
      Campylobacter likely incurs a fitness cost as the mutant strains showed slower
      growth rates in antibiotic-free media.

PMID- 24728009
TI  - Centimeter-scale-homogeneous SERS substrates with seven-order global enhancement
      through thermally controlled plasmonic nanostructures.
AB  - Highly homogeneous surface-enhanced Raman scattering (SERS) substrates were
      produced on the centimeter scale by annealing solution-processed gold
      nanoparticles into plasmonic nanoislands. The average size and separation of the
      nanoislands are controlled by tuning the annealing temperature. SERS measurements
      yield a global enhancement factor as large as 10(7) over an area of 2 * 2 cm(2)
      for samples annealed at temperatures ranging from 150 to 200  degrees C. Spectral
      "mapping" of the SERS signal shows a homogeneous distribution of hotspots with
      high contrast over the entire substrate. The relative standard deviation of the
      SERS signal is less than 5.4% over an area of 50 * 50 MUm(2). Theoretical
      simulations show strong dependence of the near-field electromagnetic enhancement
      on the size and the separation gap of the gold nanoislands. Both average gap size
      and average nanoisland size increase with an increase in annealing temperature.
      Intensive plasmonic coupling between the adjacent gold nanoislands leads to
      broadband resonance for samples annealed at 150 and 200  degrees C; thus, the
      laser excitation within the spectrum of plasmon resonance at 633 or 785 nm
      produced significantly enhanced SERS for 4-mercaptopyridine molecules modified on
      the gold nanoislands. 

PMID- 24728008
TI  - Redefining the PF06864 Pfam family based on Burkholderia pseudomallei PilO2(Bp) S
      SAD crystal structure.
AB  - Type IV pili are surface-exposed filaments and bacterial virulence factors,
      represented by the Tfpa and Tfpb types, which assemble via specific machineries.
      The Tfpb group is further divided into seven variants, linked to heterogeneity in
      the assembly machineries. Here we focus on PilO2(Bp), a protein component of the
      Tfpb R64 thin pilus variant assembly machinery from the pathogen Burkholderia
      pseudomallei. PilO2(Bp) belongs to the PF06864 Pfam family, for which an improved
      definition is presented based on newly derived Hidden Markov Model (HMM)
      profiles. The 3D structure of the N-terminal domain of PilO2(Bp) (N-PilO2(Bp)),
      here reported, is the first structural representative of the PF06864 family. N
      PilO2(Bp) presents an actin-like ATPase fold that is shown to be present in BfpC,
      a different variant assembly protein; the new HMM profiles classify BfpC as a
      PF06864 member. Our results provide structural insight into the PF06864 family
      and on the Type IV pili assembly machinery.

PMID- 24728011
TI  - An AIE active monoimidazolium skeleton: high selectivity and fluorescence turn-on
      for H2PO4- in acetonitrile and ClO4- in water.
AB  - We disclose herein a monoimidazolium skeleton 1 with an aggregation-induced
      emission (AIE) characteristic. This fluorogenic skeleton exhibited high
      selectivity and fluorescence turn-on for H2PO4(-) in acetonitrile and ClO4(-) in
      water.

PMID- 24728010
TI  - Incidence of active pulmonary tuberculosis in patients with coincident filarial
      and/or intestinal helminth infections followed longitudinally in South India.
AB  - BACKGROUND: Filarial (and other helminth) infections are known to modulate
      mycobacteria-specific pro-inflammatory cytokine responses necessary for
      maintaining latency in tuberculosis (TB). We sought to address whether helminth
      co-infection alters progression to active pulmonary TB in a co-endemic area of
      South India. METHODS/PRINCIPAL FINDINGS: Incidence of active pulmonary TB was
      assessed in 5096 subjects from five villages among helminth-infected (hel+) and 
      uninfected (hel-) groups. Baseline stool examinations, circulating filarial
      antigen, and tuberculin skin testing (PPD) were performed along with chest
      radiographs, sputum microscopy, and culture. During three follow-up visits each
      2.5 years, patients were assessed using PPD tests and questionnaires and--for
      those with potential symptoms of TB--sputum microscopy and culture. Of the 5096
      subjects, 1923 were found to be hel+ and 3173 were hel-. Follow up interval stool
      examination could not be performed. In each group, 21 developed active TB over
      the course of the study. After adjusting for sex, age, BCG vaccination status,
      and PPD positivity, no difference was seen in active TB incidence between hel+
      and hel- groups either at baseline (relative risk (RR) 1.60; 95% confidence
      interval (CI): 0.69, 3.71, P = 0.27), or when followed prospectively (RR 1.24;
      95% CI: 0.48, 3.18, P = 0.66). CONCLUSIONS/SIGNIFICANCE: Our findings suggest
      that, despite the immunomodulatory effects of helminth infection, baseline co
      morbid infection with these parasites had little effect on the clinical
      progression from latent to active pulmonary TB.

PMID- 24728012
TI  - Timescales for detecting a significant acceleration in sea level rise.
AB  - There is observational evidence that global sea level is rising and there is
      concern that the rate of rise will increase, significantly threatening coastal
      communities. However, considerable debate remains as to whether the rate of sea
      level rise is currently increasing and, if so, by how much. Here we provide new
      insights into sea level accelerations by applying the main methods that have been
      used previously to search for accelerations in historical data, to identify the
      timings (with uncertainties) at which accelerations might first be recognized in
      a statistically significant manner (if not apparent already) in sea level records
      that we have artificially extended to 2100. We find that the most important
      approach to earliest possible detection of a significant sea level acceleration
      lies in improved understanding (and subsequent removal) of interannual to
      multidecadal variability in sea level records. 

PMID- 24728013
TI  - Clinical oxygen enhancement ratio of tumors in carbon ion radiotherapy: the
      influence of local oxygenation changes.
AB  - The effect of carbon ion radiotherapy on hypoxic tumors has recently been
      questioned because of low linear energy transfer (LET) values in the spread-out
      Bragg peak (SOBP). The aim of this study was to investigate the role of hypoxia
      and local oxygenation changes (LOCs) in fractionated carbon ion radiotherapy.
      Three-dimensional tumors with hypoxic subvolumes were simulated assuming
      interfraction LOCs. Different fractionations were applied using a clinically
      relevant treatment plan with a known LET distribution. The surviving fraction was
      calculated, taking oxygen tension, dose and LET into account, using the
      repairable-conditionally repairable (RCR) damage model with parameters for human
      salivary gland tumor cells. The clinical oxygen enhancement ratio (OER) was
      defined as the ratio of doses required for a tumor control probability of 50% for
      hypoxic and well-oxygenated tumors. The resulting OER was well above unity for
      all fractionations. For the hypoxic tumor, the tumor control probability was
      considerably higher if LOCs were assumed, rather than static oxygenation. The
      beneficial effect of LOCs increased with the number of fractions. However, for
      very low fraction doses, the improvement related to LOCs did not compensate for
      the increase in total dose required for tumor control. In conclusion, our results
      suggest that hypoxia can influence the outcome of carbon ion radiotherapy because
      of the non-negligible oxygen effect at the low LETs in the SOBP. However, if LOCs
      occur, a relatively high level of tumor control probability is achievable with a
      large range of fractionation schedules for tumors with hypoxic subvolumes, but
      both hyperfractionation and hypofractionation should be pursued with caution. 

PMID- 24728014
TI  - Re-evaluation of the inheritance for root-knot nematode resistance in the Upland
      cotton germplasm line M-120 RNR revealed two epistatic QTLs conferring
      resistance.
AB  - KEY MESSAGE: We report a second major QTL for root-knot nematode resistance in
      the highly resistant Upland cotton line M-120RNR and show epistasis between two
      resistant QTLs with different mechanisms conferring resistance. In an earlier
      study, we identified a major QTL on Chromosome 11 associated with resistance to
      root-knot nematode in the M-120 RNR Upland cotton line (Gossypium hirsutum L.) of
      the Auburn 623 RNR source. Herein, we re-evaluated the genetics of the resistance
      to root-knot nematode in the M-120 RNR * Pima S-6 population by linkage mapping
      using recently published SSR markers. The QTL analysis detected two regions
      significantly associated with the resistance phenotype. In addition to the QTL
      previously identified on Chromosome 11 (qMi-C11), a major QTL was identified on
      Chromosome 14 (qMi-C14). The resistance locus on qMi-C11 originated from the
      Clevewilt parent, while the qMi-C14 locus originated from the other resistant
      parent, Mexico Wild Jack Jones. The qMi-C14 locus had logarithms of odds score of
      17 and accounted for 45 % of the total phenotype variation in egg production. It
      was also associated with galling index, but the percent variation explained was
      only 6 %, suggesting that the qMi-C11 locus had a much stronger effect on root
      gall suppression than egg production, while the qMi-C14 locus had a stronger
      effect on egg production than galling. The results also suggest that the
      transgressive segregation observed in the development of Auburn 623 RNR was due
      to the pyramiding of at least two main effect QTLs as well as an additive-by
      additive epistatic effects between the two resistant loci. The SSRs markers
      tightly linked to the qMi-C11 and qMi-C14 loci will greatly facilitate the
      improvement of RKN resistance in cotton via marker-assisted breeding.

PMID- 24728023
TI  - The utility of imputed matched sets. Analyzing probabilistically linked databases
      in a low information setting.
AB  - OBJECTIVE: To compare results from high probability matched sets versus imputed
      matched sets across differing levels of linkage information. METHODS: A series of
      linkages with varying amounts of available information were performed on two
      simulated datasets derived from multiyear motor vehicle crash (MVC) and hospital
      databases, where true matches were known. Distributions of high probability and
      imputed matched sets were compared against the true match population for occupant
      age, MVC county, and MVC hour. Regression models were fit to simulated log
      hospital charges and hospitalization status. RESULTS: High probability and
      imputed matched sets were not significantly different from occupant age, MVC
      county, and MVC hour in high information settings (p > 0.999). In low information
      settings, high probability matched sets were significantly different from
      occupant age and MVC county (p < 0.002), but imputed matched sets were not (p >
      0.493). High information settings saw no significant differences in inference of
      simulated log hospital charges and hospitalization status between the two
      methods. High probability and imputed matched sets were significantly different
      from the outcomes in low information settings; however, imputed matched sets were
      more robust. CONCLUSIONS: The level of information available to a linkage is an
      important consideration. High probability matched sets are suitable for high to
      moderate information settings and for situations involving case-specific
      analysis. Conversely, imputed matched sets are preferable for low information
      settings when conducting population-based analyses.

PMID- 24728015
TI  - Spatiotemporal path discontinuities of wavepackets propagating across a meta
      atom.
AB  - The realization of phase discontinuities across metasurfaces has led to a new
      class of reflection and refraction. Here we present theory and experiment on the
      discontinuous propagation of wavepackets across subwavelength-thickness meta
      atoms. Using acoustic waves, we observe the process of wavepackets traversing a
      meta-atom with abrupt displacements, which appear as path discontinuities on a
      space-time diagram. We construct a tunable meta-atom from two coupled resonators
      at ~500 Hz, map the spatiotemporal trajectories of individual sonic pulses, and
      reveal discontinuities at the meta-atom where the pulses exit at a time ~50 ms
      ahead or behind their arrivals. Applications include thin acoustic metasurface
      lenses.

PMID- 24728027
TI  - Fibromyalgia and non-celiac gluten sensitivity: a description with remission of
      fibromyalgia.
AB  - Fibromyalgia (FM) syndrome is a disabling clinical condition of unknown cause,
      and only symptomatic treatment with limited benefit is available. Gluten
      sensitivity that does not fulfill the diagnostic criteria for celiac disease (CD)
      is increasingly recognized as a frequent and treatable condition with a wide
      spectrum of manifestations that overlap with the manifestations of FM, including
      chronic musculoskeletal pain, asthenia, and irritable bowel syndrome. The aim of
      this report was to describe 20 selected patients with FM without CD who improved
      when placed on a gluten-free diet. An anti-transglutaminase assay, duodenal
      biopsy, and HLA typing were performed in all cases. CD was ruled out by negative
      anti-transglutaminase assay results and absence of villous atrophy in the
      duodenal biopsy. All patients had intraepithelial lymphocytosis without villous
      atrophy. Clinical response was defined as achieving at least one of the following
      scenarios: remission of FM pain criteria, return to work, return to normal life,
      or the discontinuation of opioids. The mean follow-up period was 16 months (range
      5-31). This observation supports the hypothesis that non-celiac gluten
      sensitivity may be an underlying cause of FM syndrome.

PMID- 24728028
TI  - Assessment of the effectiveness of interferential current therapy and TENS in the
      management of carpal tunnel syndrome: a randomized controlled study.
AB  - We assessed the effectiveness of interferential current (IFC) and transcutaneous
      electrical nerve stimulation (TENS) therapies in the management of carpal tunnel
      syndrome (CTS) compared with splint therapy, a standard treatment modality for
      CTS. This was a prospective, single-blinded, single-center, randomized, three
      group parallel intervention study of 3 weeks duration. Efficacy was examined in
      the third week after the end of treatments. Subjects were assigned randomly to
      one of three groups: group I patients received splint therapy, group II patients
      received TENS applied on the palmar surface of the hand and the carpal tunnel,
      and group III patients underwent IFC therapy applied on the palmar surface of the
      hand and the volar surface of the forearm. TENS and ICF treatments were applied
      five times weekly for a total of 15 sessions. Group 1 patients were stabilized
      with volar wrist splints for 3 weeks. The efficacy of the therapies was assessed
      before initiation of therapy and at 3 weeks after completion of therapy using a
      visual analog scale (VAS), a symptom severity scale, the functional capacity
      scale of the BCTQ, and measurement of median nerve motor distal latency (mMDL)
      and median sensory nerve conduction velocity (mSNCV). Groups were compared
      pairwise using the Mann-Whitney U test to identify the source of differences
      between groups. The Wilcoxon test was used to analyze changes in variables over
      time within a group. In the VAS, BCTQ, MDL, and mSNCV, no significant difference
      was observed between the groups (p > 0.05). In the VAS, BCTQ, and mSNCV,
      statistically significant improvements were detected in all groups (p < 0.05).
      There was no statistically significant difference between TENS and splint therapy
      with respect to improvement in clinical scores, whereas IFC therapy provided a
      significantly greater improvement in VAS, mMDL, and mSNCV values than splint
      therapy (VAS: 4.80 +/- 1.18 and 6.37 +/- 1.18; p = 0.001, mMDL: 3.89 +/- 0.88 and
      4.06 +/- 0.61; p = 0.001, mSNCV: 41.80 +/- 1.76 and 40.75 +/- 1.48; p = 0.010).
      IFC therapy provided a significantly greater improvement in VAS, symptom
      severity, functional capacity, and mMDL and mSNCV values than TENS therapy (VAS:
      4.80 +/- 1.18 and 6.68 +/- 1.42; p < 0.001, symptom severity: 2.70 +/- 1.03 and
      3.37 +/- 1.21; p = 0.015, functional capacity: 1.90 +/- 1.21 and 2.50 +/- 0.78; p
      = 0.039, mMDL: 3.89 +/- 0.88 and 4.06 +/- 0.88; p = 0.003, and mSNCV: 41.80 +/-
      1.76 and 41.38 +/- 1.78; p = 0.021). IFC may be considered a new and safe
      therapeutic option for the treatment of CTS.

PMID- 24728029
TI  - Genital aphthosis in Behcet's disease: is it associated with less eye
      involvement?
AB  - Behcet's disease (BD) is a multisystem disease classified among the vasculitides
      with various clinical features. Genital aphthosis (GA) is one of the major
      manifestations of BD. The aim of this study was to evaluate the characteristics
      of BD patients with GA. A cross-sectional sample of BD patients registered in 37
      years was selected. We determined clinical and laboratory features of BD patients
      with GA (GA cases) and compared them with the patients who never developed GA
      (non-GA cases). The comparisons were performed by the chi-square test and
      logistic regression analysis. Odds ratios (ORs) with 95 % confidence intervals
      were calculated to estimate the precision of ORs. Among 6,935 BD patients, 4,489
      cases (64.7 %) were ascribed to GA cases. Male to female ratio (1.11:1.00 vs.
      1.48:1.00 OR 0.753, P value <0.001) and mean age of disease onset (OR = 0.9, P
      value <0.001) were lower in GA subset. In GA cases, oral aphthosis (OA) was a
      more common onset manifestation (OR 2.250, P value <0.001), while uveitis (OR
      0.140, P value <0.001) and retinal vasculitis (OR 0.077, P value <0.001) were
      less common at the disease onset. In the whole course of disease, eye involvement
      was less common in GA cases (OR 0.215, P value <0.001). On the contrary, OA (OR
      19.698, P value <0.001), skin (OR 1.762, P value <0.001), joint (OR 1.257, P
      value = 0.001), gastrointestinal (OR 1.302, P value = 0.009), neurological (OR
      1.624, P value <0.001) and vascular involvements (OR 1.362, P value <0.001),
      epididymitis (OR 1.596, P value <0.001), positive pathergy test (OR 1.209, P
      value <0.001) and positive familial history of OA (OR 1.325, P value <0.001) were
      more common in GA subset. This study showed that GA subset of BD is associated
      with less eye involvement but higher rates of other BD manifestations.

PMID- 24728030
TI  - Longitudinal practice patterns of prophylaxis of glucocorticoid-induced
      osteoporosis in patients with polymyalgia rheumatica.
AB  - The aim of this study was to analyze the longitudinal practice patterns of
      prophylaxis of glucocorticoid-induced osteoporosis in patients with polymyalgia
      rheumatica (PMR). Patients diagnosed with PMR were collected retrospectively in
      two rheumatology departments. In addition to demographic and diagnostic criteria,
      the chart review included the following information at baseline and at follow-up:
      doses of prednisone, prescription of calcium, vitamin D and bisphosphonates, bone
      mass measurement (BMD) and fragility fractures. We analyzed the percentage of
      patients undergoing BMD and were prescribed a bisphosphonate over the years. We
      evaluated 158 patients: 117 of them were women, mean age was 73 years, and they
      had an average follow-up of 4.8 years. 104 patients (66 %) received osteoporosis
      medication during the first visit, 44 of them were given bisphosphonate. During
      follow-up, another 30 treatments with bisphosphonate were added (46 % overall)
      while 37 cases (23 %) received no treatment with calcium or bisphosphonate. BMD
      was performed in 111 patients (69 %; 53 % of males and 76 % of females). Factors
      associated with the use of bisphosphonates were female sex (OR 4.4, 95 % CI 4.02
      4.86), BMD (OR 2.4, 95 % CI 2.05-2.78) and commencement of treatment after the
      year 2005 (54 vs 37 %, OR 1.93, 95 % CI 1.60-2.26). No significant differences
      were found with age, initial doses of prednisone or the hospital. According to
      recent prevention guidelines, treatment with biphosphonate should have been
      administered in more than 90 % of patients. Although prophylaxis of
      glucocorticoid-induced osteoporosis in patients with PMR has increased in the
      recent years, many patients do not receive prophylaxis with bisphosphonate during
      the first visit.

PMID- 24728031
TI  - Functional FCGR3A 158 V/F and IL-6 -174 C/G polymorphisms predict response to
      biologic therapy in patients with rheumatoid arthritis: a meta-analysis.
AB  - The aim of this study was to investigate whether the Fc gamma receptor 3A
      (FCGR3A) 158 V/F and interleukin-6 (IL-6) promoter -174 G/C polymorphisms can
      predict the response to biologic-based therapy in patients with rheumatoid
      arthritis (RA). We conducted a meta-analysis of studies on the association
      between the FCGR3A V/F polymorphism or the IL-6 -174 C/G polymorphism and non
      responsiveness to biologic therapy in RA patients. A total of 10 studies
      involving 1,427 patients were considered. These studies consisted of seven
      studies on the FCGR3A polymorphism and three studies on the IL-6 polymorphism.
      Meta-analysis showed no association between the FCGR3A VV+VF genotype and non
      responders to biologic therapy [odds ratio (OR) 0.881, 95 % confidence interval
      (CI) 0.505-1.537, p = 0.655]. However, stratification by biologic type indicated
      an association between the FCGR3A VV+VF genotype and non-responders to rituximab
      (OR 0.566, 95 % CI 0.373-0.857, p = 0.007), but no association was found in non
      responders to tumor necrosis factor (TNF)-blockers (OR 1.337, 95 % CI 0.869
      2.056, p = 0.186). Meta-analysis revealed no association between the IL-6 CC+CG
      genotype and non-responders to the biologics (OR 3.233, 95 % CI 0.766-13.64, p =
      0.110). However, an association was found between the IL-6 CC+CG genotype and non
      responders to anti-TNF therapy (OR 8.030, 95 % CI 1.807-33.68, p = 0.006). This
      meta-analysis demonstrates that FCGR3A V allele carriers show a better response
      to rituximab, and individuals carrying the IL-6 -174 C allele show a poorer
      response to anti-TNF therapy for RA. Genotyping for these polymorphisms may be a
      useful tool for predicting the response to biologics with respect to personalized
      medicine.

PMID- 24728032
TI  - Role of the work-unit environment in the development of new shoulder pain among
      hospital workers: a longitudinal analysis.
AB  - OBJECTIVE: This study aimed to test longitudinal associations linking the work
      unit-level psychosocial and organizational work environment and biomechanical
      constraints to workers' shoulder pain in the French multi-centre cohort ORSOSA
      study of registered nurses (RN) and nursing assistants (NA). METHODS: We analyzed
      1896 female RN and NA, who were free of shoulder pain in 2006 and in the same
      position and work unit in 2008. Incident shoulder pain (SP) was defined as self
      reported pain that persists for >= 4 days and/or increases during a lateral
      movement of the arm away from the midline of the body (abduction). Both cross
      sectional and longitudinal models were built to test if work-unit-level features
      or their influences on both work tasks and individual perception of the work
      environment directly influence the risk of developing incident SP. RESULTS: RN in
      work units with understaffing issues or poor relationships reported higher levels
      of biomechanical constraints in movements and postures and a lower level of
      perceived job security and stability. NA who experienced such issues reported
      higher levels of biomechanical constraints in indirect patient-handling
      activities only. The exposure to these latter factors was associated with higher
      two-year incident SP among workers. CONCLUSION: This study shows that the work
      unit-level organizational characteristics may impact workers' musculoskeletal
      disorders by conditioning both work-task-related biomechanical exposures and
      individual perception of the working environment. In healthcare settings, primary
      prevention programs to reduce MSD would benefit from a focus on work unit level
      exposures.

PMID- 24728033
TI  - Assessing the contribution of marine protected areas to the trophic functioning
      of ecosystems: a model for the Banc d'Arguin and the Mauritanian shelf.
AB  - Most modelling studies addressed the effectiveness of marine protected areas
      (MPA) for fisheries sustainability through single species approach. Only a few
      models analysed the potential benefits of MPAs at the ecosystem level, estimating
      the potential export of fish biomass from the reserve or analysing the trophic
      relationships between organisms inside and outside the MPA. Here, we propose to
      use food web models to assess the contribution of a MPA to the trophic
      functioning of a larger ecosystem. This approach is applied to the Banc d'Arguin
      National Park, a large MPA located on the Mauritanian shelf. The ecosystem was
      modeled using Ecopath with Ecosim, a model that accounts for fisheries, food web
      structure, and some aspects of the spatial distribution of species, for the
      period 1991-2006. Gaps in knowledge and uncertainty were taken into account by
      building three different models. Results showed that the Banc d'Arguin
      contributes about 9 to 13% to the total consumption, is supporting about 23% of
      the total production and 18% of the total catch of the Mauritanian shelf
      ecosystem, and up to 50% for coastal fish. Of the 29 exploited groups, 15 depend
      on the Banc for more than 30% of their direct or indirect consumptions. Between
      1991 and 2006, the fishing pressure increased leading to a decrease in biomass
      and the catch of high trophic levels, confirming their overall overexploitation.
      Ecosim simulations showed that adding a new fleet in the Banc d'Arguin would have
      large impacts on the species with a high reliance on the Banc for food, resulting
      in a 23% decrease in the current outside MPA catches. We conclude on the
      usefulness of food web models to assess MPAs contribution to larger ecosystem
      functioning. 

PMID- 24728034
TI  - Growth and structural properties of silicene at multilayer coverage.
AB  - At monolayer coverage, silicene on Ag(1 1 1) may present different structural
      phases depending on the growth conditions. At multilayer coverage, only one
      structural phase has been reported: the [Formula: see text] phase. However, no
      link between the structural arrangement of the monolayer and that of the
      multilayer has been addressed. In this paper, reporting experimental work based
      on low-energy electron diffraction and scanning tunneling microscopy, we focus on
      the structural aspects of a multilayer film of silicene. We demonstrate that it
      exhibits one structural arrangement, namely the [Formula: see text] form, but
      with different domain orientations resulting from the structural properties of
      the initial wetting monolayer. 

PMID- 24728036
TI  - Oral arsenic trioxide-based regimen as salvage treatment for relapsed or
      refractory mantle cell lymphoma.
AB  - BACKGROUND: Mantle cell lymphoma (MCL) is aggressive, and relapsed/refractory
      disease has poor outcomes. PATIENTS AND METHODS: Thirty-nine patients (men = 34,
      women = 5) at 64 (41-82) years of age with relapsed/refractory MCL, ineligible
      for high-dose chemotherapy and had received 2 (1-5) prior regimens, were treated
      with a continuous oral regimen, comprising oral arsenic trioxide (oral-As2O3),
      chlorambucil and ascorbic acid. RESULTS: Overall response rate was 49% (complete
      response, CR = 28%; partial response, PR = 21%). Only grade 1/2 toxicities were
      observed (hematologic: 56%, hepatic: 8%). Response was maintained in 11 patients
      (CR = 8; PR = 3), after a median of 24 (2-108) months. Independent prognostic
      factors for response were increased lactate dehydrogenase (P = 0.04) and
      unfavorable MCL international prognostic index (P = 0.04). At a median follow-up
      of 21 (1-118) months, the median progression-free survival (PFS) was 16 months,
      and overall survival (OS) 38 months. Independent prognostic factors for PFS were
      female gender (P = 0.002), and Eastern Cooperative Oncology Group (ECOG)
      performance score of 2 (P = 0.009). Independent prognostic factors for OS were
      female gender (P < 0.001), ECOG performance score of 2 (P = 0.03), non-response
      (P < 0.001), and disease progression after initial response (P = 0.05).
      CONCLUSION: An oral regimen of oral-As2O3, chlorambucil and ascorbic acid was
      active with minimal toxicity in relapsed/refractory MCL, achieving durable
      responses in ~30% of cases.

PMID- 24728038
TI  - TGFBI (betaIG-H3) is a diabetes-risk gene based on mouse and human genetic
      studies.
AB  - Transforming growth factor beta-induced (TGFBI/betaIG-H3), also known as betaig
      H3, is a protein inducible by TGFbeta1 and secreted by many cell types. It binds
      to collagen, forms part of the extracellular matrix and interacts with integrins
      on the cell surface. Recombinant TGFBI and transgenic TGFBI overexpression can
      promote both islet survival and function. In this study, we generated TGFBI KO
      mice and further assessed TGFBI function and signaling pathways in islets. Islets
      from KO mice were of normal size and quantity, and these animals were
      normoglycemic. However, KO islet survival and function was compromised in vitro.
      In vivo, KO donor islets became inferior to wild-type donor islets in achieving
      normoglycemia when transplanted into KO diabetic recipients. TGFBI KO mice were
      more prone to straptozotocin-induced diabetes than the wild-type counterpart.
      Phosphoprotein array analysis established that AKT1S1, a molecule linking the AKT
      and mTORC1 signaling pathways, was modulated by TGFBI in islets. Phosphorylation
      of four molecules in the AKT and mTORC1 signaling pathway, i.e. AKT, AKT1S1, RPS6
      and EIF4EBP1, was upregulated in islets upon TGFBI stimulation. Suppression of
      AKT activity by a chemical inhibitor, or knockdown of AKT1S1, RPS6 and EIF4EBP1
      expression by small interfering RNA, modulated islet survival, proving the
      relevance of these molecules in TGFBI-triggered signaling. Human genetic studies
      revealed that in the TGFBI gene and its vicinity, three single-nucleotide
      polymorphisms were significantly associated with type 1 diabetes risks, and one
      with type 2 diabetes risks. Our study suggests that TGFBI is a potential risk
      gene for human diabetes. 

PMID- 24728040
TI  - Anode modification with capacitive materials for a microbial fuel cell: an
      increase in transient power or stationary power.
AB  - Extensive efforts have been devoted to improve the anode performance of a
      microbial fuel cell (MFC) by using modified carbon-based anode materials, but
      most of them did not recognize that the power performance measured by the
      commonly-used varying circuit resistance (VCR) or linear sweep voltammetry (LSV)
      method was overestimated due to the effect of anode capacitance. Here, we
      examined and compared the transient power and the stationary power of a series of
      MFCs equipped with the polypyrrole-graphene oxide (PPy-GO)-modified graphite felt
      anodes. It was found that noticeable transient power was recorded when the VCR or
      LSV method was chosen for power measurements. Calculations on the contribution of
      different sources to the measured maximum power density showed that the discharge
      of bio-electrons stored in the high-capacitance anode was a dominant contributor,
      especially when the time duration (for the VCR method) was not sufficiently long
      or the scan rate (for the LSV method) was not sufficiently low. Although anode
      modification with capacitive materials can result in the increased stationary
      power obtained from the fed-batch cycle test, owing to the increases in the anode
      surface area and the number of bacteria attached to anode, the increase in the
      transient power was more remarkable. 

PMID- 24728039
TI  - Microchip electrophoresis with amperometric detection method for profiling
      cellular nitrosative stress markers.
AB  - The overproduction of nitric oxide (NO) in cells results in nitrosative stress
      due to the generation of highly reactive species such as peroxynitrite and N2O3.
      These species disrupt the cellular redox processes through the oxidation,
      nitration, and nitrosylation of important biomolecules. Microchip electrophoresis
      (ME) is a fast separation method that can be used to profile cellular nitrosative
      stress through the separation of NO and nitrite from other redox-active
      intracellular components such as cellular antioxidants. This paper describes a ME
      method with electrochemical detection (ME-EC) for the separation of intracellular
      nitrosative stress markers in macrophage cells. The separation of nitrite, azide
      (interference), iodide (internal standard), tyrosine, glutathione, and hydrogen
      peroxide (neutral marker) was achieved in under 40 s using a run buffer
      consisting of 7.5 to 10 mM NaCl, 10 mM boric acid, and 2 mM TTAC at pH 10.3 to
      10.7. Initially, NO production was monitored by the detection of nitrite (NO2(-))
      in cell lysates. There was a 2.5- to 4-fold increase in NO2(-) production in
      lipopolysaccharide (LPS)-stimulated cells. The concentration of NO2(-) inside a
      single unstimulated macrophage cell was estimated to be 1.41 mM using the method
      of standard additions. ME-EC was then used for the direct detection of NO and
      glutathione in stimulated and native macrophage cell lysates. NO was identified
      in these studies based on its migration time and rapid degradation kinetics. The
      intracellular levels of glutathione in native and stimulated macrophages were
      also compared, and no significant difference was observed between the two
      conditions. 

PMID- 24728035
TI  - Randomized trial on adjuvant treatment with FOLFIRI followed by docetaxel and
      cisplatin versus 5-fluorouracil and folinic acid for radically resected gastric
      cancer.
AB  - BACKGROUND: Some trial have demonstrated a benefit of adjuvant fluoropirimidine
      with or without platinum compounds compared with surgery alone. ITACA-S study was
      designed to evaluate whether a sequential treatment of FOLFIRI [irinotecan plus 5
      fluorouracil/folinic acid (5-FU/LV)] followed by docetaxel plus cisplatin
      improves disease-free survival in comparison with 5-FU/LV in patients with
      radically resected gastric cancer. PATIENTS AND METHODS: Patients with resectable
      adenocarcinoma of the stomach or gastroesophageal junction were randomly assigned
      to either FOLFIRI (irinotecan 180 mg/m(2) day 1, LV 100 mg/m(2) as 2 h infusion
      and 5-FU 400 mg/m(2) as bolus, days 1 and 2 followed by 600 mg/m(2)/day as 22 h
      continuous infusion, q14 for four cycles) followed by docetaxel 75 mg/m(2) day 1,
      cisplatin 75 mg/m(2) day 1, q21 for three cycles (sequential arm) or De Gramont
      regimen (5-FU/LV arm). RESULTS: From February 2005 to August 2009, 1106 patients
      were enrolled, and 1100 included in the analysis: 562 in the sequential arm and
      538 in the 5-FU/LV arm. With a median follow-up of 57.4 months, 581 patients
      recurred or died (297 sequential arm and 284 5-FU/LV arm), and 483 died (243 and
      240, respectively). No statistically significant difference was detected for both
      disease-free [hazard ratio (HR) 1.00; 95% confidence interval (CI): 0.85-1.17; P
      = 0.974] and overall survival (OS) (HR 0.98; 95% CI: 0.82-1.18; P = 0.865). Five
      year disease-free and OS rates were 44.6% and 44.6%, 51.0% and 50.6% in the
      sequential and 5-FU/LV arm, respectively. CONCLUSIONS: A more intensive regimen
      failed to show any benefit in disease-free and OS versus monotherapy. CLINICAL
      TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01640782.

PMID- 24728037
TI  - Estimation and partitioning of (co)heritability of inflammatory bowel disease
      from GWAS and immunochip data.
AB  - As custom arrays are cheaper than generic GWAS arrays, larger sample size is
      achievable for gene discovery. Custom arrays can tag more variants through denser
      genotyping of SNPs at associated loci, but at the cost of losing genome-wide
      coverage. Balancing this trade-off is important for maximizing experimental
      designs. We quantified both the gain in captured SNP-heritability at known
      candidate regions and the loss due to imperfect genome-wide coverage for
      inflammatory bowel disease using immunochip (iChip) and imputed GWAS data on
      61,251 and 38.550 samples, respectively. For Crohn's disease (CD), the iChip and
      GWAS data explained 19 and 26% of variation in liability, respectively, and SNPs
      in the densely genotyped iChip regions explained 13% of the SNP-heritability for
      both the iChip and GWAS data. For ulcerative colitis (UC), the iChip and GWAS
      data explained 15 and 19% of variation in liability, respectively, and the dense
      iChip regions explained 10 and 9% of the SNP-heritability in the iChip and the
      GWAS data. From bivariate analyses, estimates of the genetic correlation in risk
      between CD and UC were 0.75 (SE 0.017) and 0.62 (SE 0.042) for the iChip and GWAS
      data, respectively. We also quantified the SNP-heritability of genomic regions
      that did or did not contain the previous 163 GWAS hits for CD and UC, and SNP
      heritability of the overlapping loci between the densely genotyped iChip regions
      and the 163 GWAS hits. For both diseases, over different genomic partitioning,
      the densely genotyped regions on the iChip tagged at least as much variation in
      liability as in the corresponding regions in the GWAS data, however a certain
      amount of tagged SNP-heritability in the GWAS data was lost using the iChip due
      to the low coverage at unselected regions. These results imply that custom arrays
      with a GWAS backbone will facilitate more gene discovery, both at associated and
      novel loci.

PMID- 24728043
TI  - Catalytic production of cyclic carbonates mediated by lanthanide phenolates under
      mild conditions.
AB  - Readily available lanthanide complexes stabilized by a bridged poly(phenolate)
      ligand have been used for the first time as efficient catalysts for the insertion
      of CO2 into epoxides to generate cyclic carbonates with high activity, high
      selectivity, and a wide substrate scope under mild conditions. 

PMID- 24728042
TI  - Resistance to systemic inflammation and multi organ damage after global
      ischemia/reperfusion in the arctic ground squirrel.
AB  - INTRODUCTION: Cardiac arrest (CA) and hemorrhagic shock (HS) are two clinically
      relevant situations where the body undergoes global ischemia as blood pressure
      drops below the threshold necessary for adequate organ perfusion. Resistance to
      ischemia/reperfusion (I/R) injury is a characteristic of hibernating mammals. The
      present study sought to determine if arctic ground squirrels (AGS) are protected
      from systemic inflammation and multi organ damage after CA- or HS-induced global
      I/R and if, for HS, this protection is dependent upon their hibernation season.
      METHODS: For CA, rats and summer euthermic AGS (AGS-EU) were asphyxiated for 8
      min, inducing CA. For HS, rats, AGS-EU, and winter interbout arousal AGS (AGS
      IBA) were subject to HS by withdrawing blood to a mean arterial pressure of 35
      mmHg and maintaining that pressure for 20 min before reperfusion with Ringers.
      For both I/R models, body temperature (Tb) was kept at 36.5-37.5 degrees C. After
      reperfusion, animals were monitored for seven days (CA) or 3 hrs (HS) then
      tissues and blood were collected for histopathology, clinical chemistries, and
      cytokine level analysis (HS only). For the HS studies, additional groups of rats
      and AGS were monitored for three days after HS to access survival and
      physiological impairment. RESULTS: Rats had increased serum markers of liver
      damage one hour after CA while AGS did not. For HS, AGS survived 72 hours after
      I/R whereas rats did not survive overnight. Additionally, only rats displayed an
      inflammatory response after HS. AGS maintained a positive base excess, whereas
      the base excess in rats was negative during and after hemorrhage. CONCLUSIONS:
      Regardless of season, AGS are resistant to organ damage, systemic inflammation,
      and multi organ damage after systemic I/R and this resistance is not dependent on
      their ability to become decrease Tb during insult but may stem from an altered
      acid/base and metabolic response during I/R.

PMID- 24728044
TI  - Chlamydia trachomatis and risk of cervical intraepithelial neoplasia grade 3 or
      worse in women with persistent human papillomavirus infection: a cohort study.
AB  - OBJECTIVES: Some studies suggest that Chlamydia trachomatis (CT) enhances
      cervical carcinogenesis; however, a possible confounding effect of persistent
      human papillomavirus (HPV) infection was not addressed. We examined the potential
      role of CT infection in the development of subsequent cervical intraepithelial
      neoplasia grade 3 or worse (CIN3+) in women with prevalent HPV infection and in a
      subgroup of women with persistent HPV infection. METHODS: Participants in this
      population-based cohort study underwent a structured interview, including history
      of CT infection, and subsequently cervical exfoliated cells were obtained for HPV
      DNA and CT DNA testing. Women with high-risk HPV DNA infection and no prevalent
      cervical disease constituted the overall study population (n=1390). A subgroup of
      women with persistent HPV infection (n=320) was also identified. All women were
      passively followed for development of cervical lesions in the national Pathology
      Data Bank. HRs and 95% CIs for CIN3+ during follow-up (up to 19 years) were
      estimated in an accelerated failure time model. RESULTS: Women who reported more
      than one CT infection had a statistically significantly increased risk of CIN3+
      (high-risk HPV-positive, HR=2.51, 95% CI 1.44 to 4.37) (persistent HPV infection,
      HR=3.65, 95% CI 1.53 to 8.70). We found no association between CT DNA and
      subsequent risk of CIN3+ among women who were HPV-positive or had a persistent
      HPV infection at baseline. CONCLUSIONS: Repeated CT infections increased the risk
      of CIN3+ among women with prevalent as well as persistent high-risk HPV
      infection.

PMID- 24728046
TI  - Water-soluble multidentate polymers compactly coating Ag2S quantum dots with
      minimized hydrodynamic size and bright emission tunable from red to second near
      infrared region.
AB  - Hydrodynamic size-minimized quantum dots (QDs) have outstanding physicochemical
      properties for applications in multicolor molecular and cellular imaging at the
      level of single molecules and nanoparticles. In this study, we have reported the
      aqueous synthesis of Ag2S QDs by using thiol-based multidentate polymers as
      capping reagents. By regulating the composition of the precursors (AgNO3 and
      sulfur-N2H4.H2O complex) and multidentate polymers (poly(acrylic acid)-graft
      cysteamine-graft-ethylenediamine), as well as the reaction time, Ag2S QDs (2.6
      3.7 nm) are prepared, displaying tunable photoluminescence (PL) emission from red
      to the second near-infrared region (687-1096 nm). The small hydrodynamic
      thickness (1.6-1.9 nm) of the multidentate polymers yields a highly compact
      coating for the QDs, which results in the bright fluorescent QDs with high PL
      quantum yields (QYs: 14.2-16.4%). Experimental results confirm that the QDs have
      high PL stability and ultralow cytotoxicity, as well as high PLQYs and small
      hydrodynamic sizes (4.5-5.6 nm) similar to fluorescent proteins (27-30 kDa),
      indicating the feasibility of highly effective PL imaging in cells and living
      animals. 

PMID- 24728045
TI  - 3D non-woven polyvinylidene fluoride scaffolds: fibre cross section and
      texturizing patterns have impact on growth of mesenchymal stromal cells.
AB  - Several applications in tissue engineering require transplantation of cells
      embedded in appropriate biomaterial scaffolds. Such structures may consist of 3D
      non-woven fibrous materials whereas little is known about the impact of mesh
      size, pore architecture and fibre morphology on cellular behavior. In this study,
      we have developed polyvinylidene fluoride (PVDF) non-woven scaffolds with round,
      trilobal, or snowflake fibre cross section and different fibre crimp patterns
      (10, 16, or 28 needles per inch). Human mesenchymal stromal cells (MSCs) from
      adipose tissue were seeded in parallel on these scaffolds and their growth was
      compared. Initial cell adhesion during the seeding procedure was higher on non
      wovens with round fibres than on those with snowflake or trilobal cross sections.
      All PVDF non-woven fabrics facilitated cell growth over a time course of 15 days.
      Interestingly, proliferation was significantly higher on non-wovens with round or
      trilobal fibres as compared to those with snowflake profile. Furthermore,
      proliferation increased in a wider, less dense network. Scanning electron
      microscopy (SEM) revealed that the MSCs aligned along the fibres and formed
      cellular layers spanning over the pores. 3D PVDF non-woven scaffolds support
      growth of MSCs, however fibre morphology and mesh size are relevant:
      proliferation is enhanced by round fibre cross sections and in rather wide-meshed
      scaffolds. 

PMID- 24728047
TI  - Ostwald's dilution law challenge.

PMID- 24728048
TI  - Solution to blue garlic challenge.

PMID- 24728049
TI  - Sensitive detection of T4 polynucleotide kinase activity based on coupled
      exonuclease reaction and nicking enzyme-assisted fluorescence signal
      amplification.
AB  - As a prominent member of the 5'-kinase family, T4 polynucleotide kinase (PNK)
      plays an important role in gene function regulations, and the study of PNK
      activity and its potential inhibitors is significant for research related to the
      DNA phosphorylation process. Here, we proposed a novel strategy for the detection
      of PNK activity and its inhibition, which combines exonuclease enzyme reaction
      and nicking enzyme-assisted fluorescence signal amplification. Through recycling
      cleavage of DNA fluorescence probe for signal amplification, a highly sensitive
      PNK sensing platform is developed, and a very low detection limit of 0.05 mU/mL
      is achieved, which is better than or comparable to that of the previously
      reported PNK assays. The present approach adopts a simple separation-free
      procedure in which the enzyme assay is conducted in homogeneous solutions.
      Additionally, the inhibitory effects of several known kinase inhibitors on PNK
      have been successfully detected. Since the proposed assay exhibits the advantages
      of high sensitivity and simplicity, it holds great potential in providing a
      promising platform for convenient and highly sensitive detection of PNK activity
      and its inhibitors. 

PMID- 24728051
TI  - IPCA-CMI: an algorithm for inferring gene regulatory networks based on a
      combination of PCA-CMI and MIT score.
AB  - Inferring gene regulatory networks (GRNs) is a major issue in systems biology,
      which explicitly characterizes regulatory processes in the cell. The Path
      Consistency Algorithm based on Conditional Mutual Information (PCA-CMI) is a well
      known method in this field. In this study, we introduce a new algorithm (IPCA
      CMI) and apply it to a number of gene expression data sets in order to evaluate
      the accuracy of the algorithm to infer GRNs. The IPCA-CMI can be categorized as a
      hybrid method, using the PCA-CMI and Hill-Climbing algorithm (based on MIT
      score). The conditional dependence between variables is determined by the
      conditional mutual information test which can take into account both linear and
      nonlinear genes relations. IPCA-CMI uses a score and search method and defines a
      selected set of variables which is adjacent to one of X or Y. This set is used to
      determine the dependency between X and Y. This method is compared with the method
      of evaluating dependency by PCA-CMI in which the set of variables adjacent to
      both X and Y, is selected. The merits of the IPCA-CMI are evaluated by applying
      this algorithm to the DREAM3 Challenge data sets with n variables and n samples
      (n = 10, 50, 100) and to experimental data from Escherichia coil containing 9
      variables and 9 samples. Results indicate that applying the IPCA-CMI improves the
      precision of learning the structure of the GRNs in comparison with that of the
      PCA-CMI.

PMID- 24728052
TI  - Expression of the EGF family in gastric cancer: downregulation of HER4 and its
      activating ligand NRG4.
AB  - Gastric cancer is a major cause of cancer-related deaths in both men and women.
      The epidermal growth factor receptors are EGFR, HER2, HER3 and HER4. Of the four
      epidermal growth factor receptors, EGFR and HER2 are well-known oncogenes
      involved in gastric cancer. Little, however, is known about the role played by
      HER3 and HER4 in this disease. We obtained paired samples from the tumor and the
      adjacent normal tissue from the same patient undergoing surgery for gastric
      cancer. Using RT-qPCR, we quantified the mRNA expression of the four receptors
      including the HER4 splicing isoforms and all the ligands activating these
      receptors. Using immunohistochemistry, the protein expression of HER4 was also
      quantified. We found that HER2 mRNA expression was upregulated in the tumor
      tissue compared to the matched normal tissue (p = 0.0520). All ligands with
      affinity for EGFR were upregulated, whereas the expression of EGFR was unchanged.
      Interestingly, we found the mRNA expression of HER4 (p = 0.0002) and its ligand
      NRG4 (p = 0.0009) to be downregulated in the tumor tissue compared to the matched
      normal tissue. HER4 downregulation was demonstrated for all the alternatively
      spliced isoforms of this receptor. These results support the involvement of EGFR
      and HER2 in gastric cancer and suggest an interesting association of reduced HER4
      expression with development of gastric cancer. 

PMID- 24728068
TI  - Treatment of psoriatic arthritis with anti-TNF agents: a systematic review and
      meta-analysis of efficacy, effectiveness and safety.
AB  - We did a systematic review and meta-analysis on the efficacy and safety of the
      anti-TNF drugs adalimumab, etanercept, golimumab and infliximab used in psoriatic
      arthritis (PsA) adult treatment. Additionally, we present results of anti-TNF use
      in real life settings. We searched Embase, Medline, Cochrane Central and LILACS,
      from inception to 11/08/2013, for studies comparing anti-TNFs with each other or
      with controls. We included nine randomized controlled trials and six
      observational studies. ACR20, ACR50, PsARC and PASI75 responses were achieved by
      more users of anti-TNF than control after up to 24 weeks of treatment. More
      participants who used etanercept and infliximab achieved ACR70. After all
      patients originally randomized to anti-TNF or placebo had used anti-TNF for at
      least 24 weeks, we observed difference only with regard to ACR70 response.
      Radiographic end points were achieved by more patients in anti-TNF group, and
      they seem to be time dependent-the longer patients use the drug the better the
      results. Etanercept and infliximab had worse results on application site
      reactions, but in general anti-TNF drugs in the regimens studied were as safe as
      control/placebo. There seems to be no difference in efficacy and effectiveness
      among anti-TNFs, but superiority head-to-head studies are still needed.
      Meanwhile, other factors should be taken into account in the choice of
      medication, such as costs and patient convenience.

PMID- 24728070
TI  - Potential role of PTPN22 in ankylosing spondylitis, comment on: associations of
      the PTPN22 and CTLA-4 genetic polymorphisms with Taiwanese ankylosing
      spondylitis.

PMID- 24728041
TI  - Automatic ROI selection in structural brain MRI using SOM 3D projection.
AB  - This paper presents a method for selecting Regions of Interest (ROI) in brain
      Magnetic Resonance Imaging (MRI) for diagnostic purposes, using statistical
      learning and vector quantization techniques. The proposed method models the
      distribution of GM and WM tissues grouping the voxels belonging to each tissue in
      ROIs associated to a specific neurological disorder. Tissue distribution of
      normal and abnormal images is modelled by a Self-Organizing map (SOM), generating
      a set of representative prototypes, and the receptive field (RF) of each SOM
      prototype defines a ROI. Moreover, the proposed method computes the relative
      importance of each ROI by means of its discriminative power. The devised method
      has been assessed using 818 images from the Alzheimer's disease Neuroimaging
      Initiative (ADNI) which were previously segmented through Statistical Parametric
      Mapping (SPM). The proposed algorithm was used over these images to parcel ROIs
      associated to the Alzheimer's Disease (AD). Additionally, this method can be used
      to extract a reduced set of discriminative features for classification, since it
      compresses discriminative information contained in the brain. Voxels marked by
      ROIs which were computed using the proposed method, yield classification results
      up to 90% of accuracy for controls (CN) and Alzheimer's disease (AD) patients,
      and 84% of accuracy for Mild Cognitive Impairment (MCI) and AD patients. 

PMID- 24728071
TI  - Adjudicated morbidity and mortality outcomes by age among individuals with HIV
      infection on suppressive antiretroviral therapy.
AB  - BACKGROUND: Non-AIDS conditions such as cardiovascular disease and non-AIDS
      defining cancers dominate causes of morbidity and mortality among persons with
      HIV on suppressive combination antiretroviral therapy. Accurate estimates of
      disease incidence and of risk factors for these conditions are important in
      planning preventative efforts. METHODS: With use of medical records, serious non
      AIDS events, AIDS events, and causes of death were adjudicated using pre
      specified criteria by an Endpoint Review Committee in two large international
      trials. Rates of serious non-AIDS which include cardiovascular disease, end-stage
      renal disease, decompensated liver disease, and non-AIDS cancer, and other
      serious (grade 4) adverse events were determined, overall and by age, over a
      median follow-up of 4.3 years for 3,570 participants with CD4+ cell count >=300
      cells/mm3 who were taking antiretroviral therapy and had an HIV RNA level <=500
      copies/mL. Cox models were used to examine the effect of age and other baseline
      factors on risk of a composite outcome of all-cause mortality, AIDS, or serious
      non-AIDS. RESULTS: Five-year Kaplan-Meier estimates of the composite outcome,
      overall and by age were 8.3% (overall), 3.6% (<40), 8.7% (40-49) and 16.1%
      (>=50), respectively (p<0.001). In addition to age, smoking and higher levels of
      interleukin-6 and D-dimer were significant predictors of the composite outcome.
      The composite outcome was dominated by serious non-AIDS events (overall 65% of
      277 participants with a composite event). Most serious non-AIDS events were due
      to cardiovascular disease and non-AIDS cancers. CONCLUSIONS: To date, few large
      studies have carefully collected data on serious non-AIDS outcomes. Thus,
      reliable estimates of event rates are scarce. Data cited here, from a
      geographically diverse cohort, will be useful for planning studies of
      interventions aimed at reducing rates of serious non-AIDS events among people
      with HIV.

PMID- 24728072
TI  - A novel allele of the P-starvation tolerance gene OsPSTOL1 from African rice
      (Oryza glaberrima Steud) and its distribution in the genus Oryza.
AB  - KEY MESSAGE: We have developed allele-specific markers for molecular breeding to
      transfer the PSTOL1 gene from Kasalath to African mega-varieties, including
      NERICAs, to improve their tolerance to P-deficient soil. The deficiency of
      phosphorus (P) in soil is a major problem in Sub-Saharan Africa due to general
      nutrient depletion and the presence of P-fixing soils. Developing rice cultivars
      with enhanced P efficiency would, therefore, represent a sustainable strategy to
      improve the livelihood of resource-poor farmers. Recently the Pup1 locus, a major
      QTL for tolerance to P deficiency in soil, was successfully narrowed-down to a
      major gene, the protein kinase OsPSTOL1 (P-starvation tolerance), which was found
      to be generally absent from modern irrigated rice varieties. Our target is to
      improve the tolerance of African mega-varieties to P deficiency through marker
      assisted introgression of PSTOL1. As a first step, we have determined the Pup1
      haplotype and surveyed the presence or absence of PSTOL1 and other genes of the
      Pup1 locus in African mega-varieties, NERICAs (New Rice for Africa) and their
      Oryza glaberrima parents. Here, we report the presence of a novel PSTOL1 allele
      in upland NERICAs that was inherited from the O. glaberrima parent CG14. This
      allele showed a 35 base-pair substitution when aligned to the Kasalath allele,
      but maintained a fully conserved kinase domain, and is present in most O.
      glaberrima accessions evaluated. In-silico and marker analysis indicated that
      many other genes of the Kasalath Pup1 locus were missing in the O. glaberrima
      genome, including the dirigent-like gene OsPupK20-2, which was shown to be
      downstream of PSTOL1. We have developed several allele-specific markers for the
      use for molecular breeding to transfer the PSTOL1 gene from Kasalath to African
      mega-varieties, including NERICAs.

PMID- 24728073
TI  - Prognostic significance of cyclin D1 expression in colorectal cancer: a meta
      analysis of observational studies.
AB  - OBJECTIVE: Cyclin D1 plays a vital role in cancer cell cycle progression and is
      overexpressed in many human cancers, including colorectal cancer (CRC). However,
      the prognostic value of cyclin D1 overexpression in colorectal cancer is
      conflicting and heterogeneous. We conducted a meta-analysis to more precisely
      evaluate its prognostic significance. METHODS: A comprehensive literature search
      for relevant studies published up to January 2014 was performed using PubMed,
      EMBASE, and ISI Web of Science. The pooled hazard ratio (HR) with 95% confidence
      intervals (CI) was used to estimate the effects. RESULTS: 22 studies with 4150
      CRC patients were selected to evaluate the association between cyclin D1 and
      overall survival (OS), disease-free survival (DFS) and clinicopathological
      parameters. In a random-effects model, the results showed that cyclin D1
      overexpression in CRC was significantly associated with both poor OS (HR = 0.73,
      95% CI: 0.63-0.85, P<0.001) and DFS (HR = 0.60, 95% CI: 0.44-0.82, P = 0.001).
      Additionally, cyclin D1 overexpression was significantly associated with more
      relative older patients (>= 60 years) (OR 0.62, 95% CI 0.44-0.89, P = 0.009),
      T3,4 tumor invasion (OR 0.70, 95% CI 0.57-0.85, P<0.001), N positive (OR 0.75,
      95% CI 0.60-0.95, P = 0.016) and distant metastasis (OR 0.60, 95% CI 0.36-0.99, P
      = 0.047) of CRC. CONCLUSION: The meta-analysis results indicated that cyclin D1
      is an unfavorable prognostic factor for CRC. Cyclin D1 overexpression might be
      associated with poor clinical outcome and some clinicopathological factors such
      as age, T category, N category and distant metastasis in CRC patients.

PMID- 24728074
TI  - Enhanced prediction of Src homology 2 (SH2) domain binding potentials using a
      fluorescence polarization-derived c-Met, c-Kit, ErbB, and androgen receptor
      interactome.
AB  - Many human diseases are associated with aberrant regulation of phosphoprotein
      signaling networks. Src homology 2 (SH2) domains represent the major class of
      protein domains in metazoans that interact with proteins phosphorylated on the
      amino acid residue tyrosine. Although current SH2 domain prediction algorithms
      perform well at predicting the sequences of phosphorylated peptides that are
      likely to result in the highest possible interaction affinity in the context of
      random peptide library screens, these algorithms do poorly at predicting the
      interaction potential of SH2 domains with physiologically derived protein
      sequences. We employed a high throughput interaction assay system to empirically
      determine the affinity between 93 human SH2 domains and phosphopeptides
      abstracted from several receptor tyrosine kinases and signaling proteins. The
      resulting interaction experiments revealed over 1000 novel peptide-protein
      interactions and provided a glimpse into the common and specific interaction
      potentials of c-Met, c-Kit, GAB1, and the human androgen receptor. We used these
      data to build a permutation-based logistic regression classifier that performed
      considerably better than existing algorithms for predicting the interaction
      potential of several SH2 domains. 

PMID- 24728075
TI  - Tumor hypomethylation at 6p21.3 associates with longer time to recurrence of high
      grade serous epithelial ovarian cancer.
AB  - To reveal biologic mechanisms underlying clinical outcome of high-grade serous
      (HGS) epithelial ovarian carcinomas (EOC), we evaluated the association between
      tumor epigenetic changes and time to recurrence (TTR). We assessed methylation at
      approximately 450,000 genome-wide CpGs in tumors of 337 Mayo Clinic (Rochester,
      MN) patients. Semi-supervised clustering of discovery (n=168) and validation
      (n=169) sets was used to determine clinically relevant methylation classes.
      Clustering identified two methylation classes based on 60 informative CpGs, which
      differed in TTR in the validation set [R vs. L class, P=2.9*10(-3), HR=0.52; 95%
      confidence interval (CI), 0.34-0.80]. Follow-up analyses considered genome-wide
      tumor mRNA expression (n=104) and CD8 T-cell infiltration (n=89) in patient
      subsets. Hypomethylation of CpGs located in 6p21.3 in the R class associated with
      cis upregulation of genes enriched in immune response processes (TAP1, PSMB8,
      PSMB9, HLA-DQB1, HLA-DQB2, HLA-DMA, and HLA-DOA), increased CD8 T-cell tumor
      infiltration (P=7.6*10(-5)), and trans-regulation of genes in immune-related
      pathways (P=1.6*10(-32)). This is the most comprehensive assessment of clinical
      outcomes with regard to epithelial ovarian carcinoma tumor methylation to date.
      Collectively, these results suggest that an epigenetically mediated immune
      response is a predictor of recurrence and, possibly, treatment response for HGS
      EOC.

PMID- 24728076
TI  - Separating Tumorigenicity from Bile Acid Regulatory Activity for Endocrine
      Hormone FGF19.
AB  - Hepatocellular carcinoma (HCC), one of the leading causes of cancer-related
      death, develops from premalignant lesions in chronically damaged livers. Although
      it is well established that FGF19 acts through the receptor complex FGFR4-beta
      Klotho (KLB) to regulate bile acid metabolism, FGF19 is also implicated in the
      development of HCC. In humans, FGF19 is amplified in HCC and its expression is
      induced in the liver under cholestatic and cirrhotic conditions. In mice, ectopic
      overexpression of FGF19 drives HCC development in a process that requires FGFR4.
      In this study, we describe an engineered FGF19 (M70) that fully retains bile acid
      regulatory activity but does not promote HCC formation, demonstrating that
      regulating bile acid metabolism is distinct and separable from tumor-promoting
      activity. Mechanistically, we show that FGF19 stimulates tumor progression by
      activating the STAT3 pathway, an activity eliminated by M70. Furthermore, M70
      inhibits FGF19-dependent tumor growth in a rodent model. Our results suggest that
      selectively targeting the FGF19-FGFR4 pathway may offer a tractable approach to
      improve the treatment of chronic liver disease and cancer.

PMID- 24728079
TI  - Vegard's law-like behavior for Mn(m)Tc(n) alloy clusters: a first-principles
      prediction.
AB  - With a view to gaining an understanding of the alloying tendency of bimetallic
      nanoalloy clusters of isoelectronic constituents, we studied the structural and
      mixing behavior of MnmTcn alloy clusters with m + n = 13 for all possible
      compositions, using first-principles electronic structure calculations. Our study
      reports a favorable mixing tendency for the alloy clusters. The average bond
      lengths of the minimum energy structures show an overall linear variation with
      concentration, indicating a Vegard's law-like variation for the nanoalloy
      clusters, though the optimized structures undergo a structural transition from a
      closed and compact structure for the Mn-rich alloy clusters to an open layered
      like structure for the Tc-rich alloy clusters. We work out a continuous and
      smooth interplay between hybridization and magnetization properties of the alloy
      clusters, which plays a vital role in the Vegard's law-like variation in their
      average bond lengths.

PMID- 24728077
TI  - Accumulation of memory precursor CD8 T cells in regressing tumors following
      combination therapy with vaccine and anti-PD-1 antibody.
AB  - Immunosuppression in the tumor microenvironment blunts vaccine-induced immune
      effectors. PD-1/B7-H1 is an important inhibitory axis in the tumor
      microenvironment. Our goal in this study was to determine the effect of blocking
      this inhibitory axis during and following vaccination against breast cancer. We
      observed that using anti-PD-1 antibody and a multipeptide vaccine (consisting of
      immunogenic peptides derived from breast cancer antigens, neu, legumain, and beta
      catenin) as a combination therapy regimen for the treatment of breast cancer
      bearing mice prolonged the vaccine-induced progression-free survival period. This
      prolonged survival was associated with increase in number of Tc1 and Tc2 CD8 T
      cells with memory precursor phenotype, CD27+IL-7RhiT-betlo, and decrease in
      number of PD-1+ dendritic cells (DC) in regressing tumors and enhanced antigen
      reactivity of tumor-infiltrating CD8 T cells. It was also observed that blockade
      of PD-1 on tumor DCs enhanced IL-7R expression on CD8 T cells. Taken together,
      our results suggest that PD-1 blockade enhances breast cancer vaccine efficacy by
      altering both CD8 T cell and DC components of the tumor microenvironment. Given
      the recent success of anti-PD-1 monotherapy, our results are encouraging for
      developing combination therapies for the treatment of patients with cancer in
      which anti-PD-1 monotherapy alone may be ineffective (i.e., PD-L1-negative
      tumors).

PMID- 24728080
TI  - A physical operation of hydrodynamic orientation of an azobenzene supramolecular
      assembly with light and sound.
AB  - Photoisomerizations of a newly designed azobenzene derivative reversibly change
      its self-assembly in a solution to form twisted supramolecular nanofibers and
      amorphous aggregates, respectively. When irradiating the sample solution with
      audible sound, the former assembly exhibits a LD response due to its hydrodynamic
      orientation, but the latter one is LD silent, in the sound-induced fluid flows. 

PMID- 24728078
TI  - Increased STAT1 signaling in endocrine-resistant breast cancer.
AB  - Proteomic profiling of the estrogen/tamoxifen-sensitive MCF-7 cell line and its
      partially sensitive (MCF-7/LCC1) and fully resistant (MCF-7/LCC9) variants was
      performed to identify modifiers of endocrine sensitivity in breast cancer.
      Analysis of the expression of 120 paired phosphorylated and non-phosphorylated
      epitopes in key oncogenic and tumor suppressor pathways revealed that STAT1 and
      several phosphorylated epitopes (phospho-STAT1(Tyr701) and phospho-STAT3(Ser727))
      were differentially expressed between endocrine resistant and parental controls,
      confirmed by qRT-PCR and western blotting. The STAT1 inhibitor EGCG was a more
      effective inhibitor of the endocrine resistant MCF-7/LCC1 and MCF-7/LCC9 lines
      than parental MCF-7 cells, while STAT3 inhibitors Stattic and WP1066 were equally
      effective in endocrine-resistant and parental lines. The effects of the STAT
      inhibitors were additive, rather than synergistic, when tested in combination
      with tamoxifen in vitro. Expression of STAT1 and STAT3 were measured by
      quantitative immunofluorescence in invasive breast cancers and matched lymph
      nodes. When lymph node expression was compared to its paired primary breast
      cancer expression, there was greater expression of cytoplasmic STAT1 (~3.1 fold),
      phospho-STAT3(Ser727) (~1.8 fold), and STAT5 (~1.5 fold) and nuclear phospho
      STAT3(Ser727) (~1.5 fold) in the nodes. Expression levels of STAT1 and STAT3
      transcript were analysed in 550 breast cancers from publicly available gene
      expression datasets (GSE2990, GSE12093, GSE6532). When treatment with tamoxifen
      was considered, STAT1 gene expression was nearly predictive of distant metastasis
      free survival (DMFS, log-rank p = 0.067), while STAT3 gene expression was
      predictive of DMFS (log-rank p<0.0001). Analysis of STAT1 and STAT3 protein
      expression in a series of 546 breast cancers also indicated that high expression
      of STAT3 protein was associated with improved survival (DMFS, p = 0.006). These
      results suggest that STAT signaling is important in endocrine resistance, and
      that STAT inhibitors may represent potential therapies in breast cancer, even in
      the resistant setting. 

PMID- 24728081
TI  - Assessing older adults' perceptions of sensor data and designing visual displays
      for ambient environments. An exploratory study.
AB  - INTRODUCTION: This article is part of the Focus Theme of Methods of Information
      in Medicine on "Using Data from Ambient Assisted Living and Smart Homes in
      Electronic Health Records". OBJECTIVES: Our objectives were to: 1) characterize
      older adult participants' perceived usefulness of in-home sensor data and 2)
      develop novel visual displays for sensor data from Ambient Assisted Living
      environments that can become part of electronic health records. METHODS: Semi
      structured interviews were conducted with community-dwelling older adult
      participants during three and six-month visits. We engaged participants in two
      design iterations by soliciting feedback about display types and visual displays
      of simulated data related to a fall scenario. Interview transcripts were analyzed
      to identify themes related to perceived usefulness of sensor data. RESULTS:
      Thematic analysis identified three themes: perceived usefulness of sensor data
      for managing health; factors that affect perceived usefulness of sensor data and;
      perceived usefulness of visual displays. Visual displays were cited as
      potentially useful for family members and health care providers. Three novel
      visual displays were created based on interview results, design guidelines
      derived from prior AAL research, and principles of graphic design theory.
      CONCLUSIONS: Participants identified potential uses of personal activity data for
      monitoring health status and capturing early signs of illness. One area for
      future research is to determine how visual displays of AAL data might be utilized
      to connect family members and health care providers through shared understanding
      of activity levels versus a more simplified view of self-management. Connecting
      informal and formal caregiving networks may facilitate better communication
      between older adults, family members and health care providers for shared
      decision-making.

PMID- 24728082
TI  - Crystal structure of the shrimp proliferating cell nuclear antigen: structural
      complementarity with WSSV DNA polymerase PIP-box.
AB  - DNA replication requires processivity factors that allow replicative DNA
      polymerases to extend long stretches of DNA. Some DNA viruses encode their own
      replicative DNA polymerase, such as the white spot syndrome virus (WSSV) that
      infects decapod crustaceans but still require host replication accessory factors.
      We have determined by X-ray diffraction the three-dimensional structure of the
      Pacific white leg shrimp Litopenaeus vannamei Proliferating Cell Nuclear Antigen
      (LvPCNA). This protein is a member of the sliding clamp family of proteins, that
      binds DNA replication and DNA repair proteins through a motif called PIP-box
      (PCNA-Interacting Protein). The crystal structure of LvPCNA was refined to a
      resolution of 3 A, and allowed us to determine the trimeric protein assembly and
      details of the interactions between PCNA and the DNA. To address the possible
      interaction between LvPCNA and the viral DNA polymerase, we docked a theoretical
      model of a PIP-box peptide from the WSSV DNA polymerase within LvPCNA crystal
      structure. The theoretical model depicts a feasible model of interaction between
      both proteins. The crystal structure of shrimp PCNA allows us to further
      understand the mechanisms of DNA replication processivity factors in non-model
      systems. 

PMID- 24728083
TI  - Dichloroacetate enhances adriamycin-induced hepatoma cell toxicity in vitro and
      in vivo by increasing reactive oxygen species levels.
AB  - A unique bioenergetic feature of cancer, aerobic glycolysis is considered an
      attractive therapeutic target for cancer therapy. Recently, dichloroacetate
      (DCA), a small-molecule metabolic modulator, was shown to reverse the glycolytic
      phenotype, induce reactive oxygen species (ROS) generation, and trigger apoptosis
      in various tumor cells. In this work, the capacity of DCA to enhance Adriamycin
      (ADM) efficacy in hepatoma cells by modulating glucose metabolism and redox
      status was evaluated. Two human hepatoma (HCC-LM3 and SMMC-7721) and a normal
      liver (LO2) cell lines were treated with DCA or ADM alone, or in combination.
      Exposure of hepatoma cells to DCA/ADM combination resulted in significantly
      decreased cell viability and increased percentage of apoptotic cells as well as
      intracellular ROS levels, in comparison with treatment with DCA or ADM alone.
      However, simultaneous treatment with the thiol antioxidant N-acetylcysteine (NAC,
      10 mmol/L) reduced the elevated ROS levels and protected hepatoma cells from the
      cytotoxic effects of DCA/ADM combination. L-buthionine-[S,R]-sulfoximine, an
      inhibitor of glutathione synthesis, enhanced hepatoma cell sensitivity to DCA/ADM
      combination. Interestingly, treatment with DCA/ADM combination did not
      significantly increase cytotoxicity in normal hepatocytes in comparison with the
      drugs administered individually. Finally, DCA reduced tumor growth and enhanced
      ADM efficacy on HCC-LM3 hepatoma in mice. Overall, our data suggest that DCA
      enhances ADM cytotoxicity in hepatoma cells by increasing intracellular ROS
      levels and provide a strong biochemical rationale for the use of DCA in
      combination with ADM for treatment of hepatoma. 

PMID- 24728084
TI  - Sex differences in the rapid detection of emotional facial expressions.
AB  - BACKGROUND: Previous studies have shown that females and males differ in the
      processing of emotional facial expressions including the recognition of emotion,
      and that emotional facial expressions are detected more rapidly than are neutral
      expressions. However, whether the sexes differ in the rapid detection of
      emotional facial expressions remains unclear. METHODOLOGY/PRINCIPAL FINDINGS: We
      measured reaction times (RTs) during a visual search task in which 44 females and
      46 males detected normal facial expressions of anger and happiness or their anti
      expressions within crowds of neutral expressions. Anti-expressions expressed
      neutral emotions with visual changes quantitatively comparable to normal
      expressions. We also obtained subjective emotional ratings in response to the
      facial expression stimuli. RT results showed that both females and males detected
      normal expressions more rapidly than anti-expressions and normal-angry
      expressions more rapidly than normal-happy expressions. However, females and
      males showed different patterns in their subjective ratings in response to the
      facial expressions. Furthermore, sex differences were found in the relationships
      between subjective ratings and RTs. High arousal was more strongly associated
      with rapid detection of facial expressions in females, whereas negatively
      valenced feelings were more clearly associated with the rapid detection of facial
      expressions in males. CONCLUSION: Our data suggest that females and males differ
      in their subjective emotional reactions to facial expressions and in the
      emotional processes that modulate the detection of facial expressions.

PMID- 24728086
TI  - Retraction: Polymorphism of 9p21.3 locus is associated with 5-year survival in
      high-risk patients with myocardial infarction.

PMID- 24728085
TI  - Ca2+ binding enhanced mechanical stability of an archaeal crystallin.
AB  - Structural topology plays an important role in protein mechanical stability.
      Proteins with beta-sandwich topology consisting of Greek key structural motifs,
      for example, I27 of muscle titin and (10)FNIII of fibronectin, are mechanically
      resistant as shown by single-molecule force spectroscopy (SMFS). In proteins with
      beta-sandwich topology, if the terminal strands are directly connected by
      backbone H-bonding then this geometry can serve as a "mechanical clamp". Proteins
      with this geometry are shown to have very high unfolding forces. Here, we set out
      to explore the mechanical properties of a protein, M-crystallin, which belongs to
      beta-sandwich topology consisting of Greek key motifs but its overall structure
      lacks the "mechanical clamp" geometry at the termini. M-crystallin is a Ca(2+)
      binding protein from Methanosarcina acetivorans that is evolutionarily related to
      the vertebrate eye lens beta and gamma-crystallins. We constructed an octamer of
      crystallin, (M-crystallin)8, and using SMFS, we show that M-crystallin unfolds in
      a two-state manner with an unfolding force ~ 90 pN (at a pulling speed of 1000
      nm/sec), which is much lower than that of I27. Our study highlights that the beta
      sandwich topology proteins with a different strand-connectivity than that of I27
      and (10)FNIII, as well as lacking "mechanical clamp" geometry, can be
      mechanically resistant. Furthermore, Ca(2+) binding not only stabilizes M
      crystallin by 11.4 kcal/mol but also increases its unfolding force by ~ 35 pN at
      the same pulling speed. The differences in the mechanical properties of apo and
      holo M-crystallins are further characterized using pulling speed dependent
      measurements and they show that Ca(2+) binding reduces the unfolding potential
      width from 0.55 nm to 0.38 nm. These results are explained using a simple two
      state unfolding energy landscape.

PMID- 24728087
TI  - alpha-Melanocyte stimulating hormone treatment in pigs does not improve early
      graft function in kidney transplants from brain dead donors.
AB  - Delayed graft function and primary non-function are serious complications
      following transplantation of kidneys derived from deceased brain dead (DBD)
      donors. alpha-melanocyte stimulating hormone (alpha-MSH) is a pleiotropic
      neuropeptide and its renoprotective effects have been demonstrated in models of
      acute kidney injury. We hypothesized that alpha-MSH treatment of the recipient
      improves early graft function and reduces inflammation following DBD kidney
      transplantation. Eight Danish landrace pigs served as DBD donors. After four
      hours of brain death both kidneys were removed and stored for 18 hours at 4
      degrees C in Custodiol preservation solution. Sixteen recipients were randomized
      in a paired design into two treatment groups, transplanted simultaneously. alpha
      MSH or a vehicle was administered at start of surgery, during reperfusion and two
      hours post-reperfusion. The recipients were observed for ten hours following
      reperfusion. Blood, urine and kidney tissue samples were collected during and at
      the end of follow-up. alpha-MSH treatment reduced urine flow and impaired
      recovery of glomerular filtration rate (GFR) compared to controls. After each
      dose of alpha-MSH, a trend towards reduced mean arterial blood pressure and
      increased heart rate was observed. alpha-MSH did not affect expression of
      inflammatory markers. Surprisingly, alpha-MSH impaired recovery of renal function
      in the first ten hours following DBD kidney transplantation possibly due to
      hemodynamic changes. Thus, in a porcine experimental model alpha-MSH did not
      reduce renal inflammation and did not improve short-term graft function following
      DBD kidney transplantation. 

PMID- 24728088
TI  - The relationship between reversed masked priming and the tri-phasic pattern of
      the lateralised readiness potential.
AB  - One of the potential explanations for negative compatibility effects (NCE) in
      subliminal motor priming tasks has been perceptual prime-target interactions.
      Here, we investigate whether the characteristic tri-phasic LRP pattern associated
      with the NCE is caused by these prime-target interactions. We found that both the
      prime-related phase and the critical reversal phase remain present even on trials
      where the target is omitted, confirming they are elicited by the prime and mask,
      not by prime-target interactions. We also report that shape and size of the
      reversal phase are associated with response speed, consistent with a causal role
      for the reversal for the subsequent response latency. Additionally, we analysed
      sequential modulation of the NCE by previous conflicting events, even though such
      conflict is subliminal. In accordance with previous literature, this modulation
      is small but significant. 

PMID- 24728089
TI  - Long-term effects of liming on health and growth of a Masson pine stand damaged
      by soil acidification in Chongqing, China.
AB  - In the last decades, the Masson pine (Pinus massoniana) forests in Chongqing,
      southwest China, have increasingly declined. Soil acidification was believed to
      be an important cause. Liming is widely used as a measure to alleviate soil
      acidification and its damage to trees, but little is known about long-term
      effects of liming on the health and growth of declining Masson pine forests. Soil
      chemical properties, health condition (defoliation and discoloration), and growth
      were evaluated following application of limestone powder (0 (unlimed control), 1,
      2, 3, and 4 t ha(-1)) in an acidified and declining Masson pine stand at
      Tieshanping (TSP) of Chongqing. Eight years after liming, in the 0-20 cm and 20
      40 cm mineral soil layers, soil pH values, exchangeable calcium (Ca) contents,
      and Ca/Al molar ratios increased, but exchangeable aluminum (Al) levels
      decreased, and as a result, length densities of living fine roots of Masson pine
      increased, with increasing dose. Mean crown defoliation of Masson pines
      (dominant, codominant and subdominant pines, according to Kraft classes 1-3)
      decreased with increasing dose, and it linearly decreased with length densities
      of living fine roots. However, Masson pines (Kraft classes 1-3) in all treatments
      showed no symptoms of discoloration. Mean current-year twig length, twig dry
      weight, needle number per twig, needle length per twig, and needle dry weight per
      twig increased with increasing dose. Over 8 years, mean height increment of
      Masson pines (Kraft classes 1-3) increased from 5.5 m in the control to 5.8, 6.9,
      8.3, and 9.5 m in the 1, 2, 3, and 4 t ha(-1) lime treatments, and their mean DBH
      (diameter at breast height) increment increased from 3.1 to 3.2, 3.8, 4.9, and
      6.2 cm, respectively. The values of all aboveground growth parameters linearly
      increased with length densities of living fine roots. Our results show that
      liming improved tree health and growth, and these effects increased with
      increasing dose.

PMID- 24728091
TI  - Diradical character from the local spin analysis.
AB  - Diradical species are analyzed in light of the local spin analysis. The atomic
      and diatomic contributions to the overall <S(2)> value are used to detect the
      diradical character of a number of molecular species mostly in their singlet
      state, for which no spin density exists. A general procedure for the
      quantification of diradical character for both singlet and triplet states is
      achieved by using a recently introduced index that measures the deviation of an
      actual molecule from an ideal system of perfectly localized spin centers. The
      index is of general applicability and can be easily determined in equal footing
      from a multireference or an open-shell single-determinant wave function. 

PMID- 24728093
TI  - A novel integrated biosensor based on co-immobilizing the mediator and
      microorganism for water biotoxicity assay.
AB  - A novel integrated biosensor for biotoxicity assay has been developed by co
      immobilizing microorganisms and mediators within a novel redox hydrogel. The
      proposed redox hydrogel acts as an immobilizing matrix both for microorganism E.
      coli and redox mediator, which was prepared by grafting the benzoquinone (BQ)
      redox mediator with gelatin/silica hybrid hydrogel (GSH). This redox hydrogel was
      characterized by UV-Vis, CV and EIS. The feasibility of the novel integrated
      biosensor for biotoxicity assay was demonstrated by measuring the heavy metal
      ions Hg(2+), Cu(2+) and Cd(2+) polluted water as the model toxicants. The results
      showed that the integrated biosensor was able to evaluate the water biotoxicity
      and the corresponding 50% inhibiting concentrations (IC50) are determined to be
      21.2 MUg mL(-1), 44 MUg mL(-1) and 79 MUg mL(-1), respectively. This integrated
      biosensor could achieve real-time monitoring of water quality and evaluation of
      biotoxicity. Moreover it avoids the waste and contamination of mediators, and
      also simplifies the assay process. 

PMID- 24728092
TI  - Selected lactic acid-producing bacterial isolates with the capacity to reduce
      Salmonella translocation and virulence gene expression in chickens.
AB  - BACKGROUND: Probiotics have been used to control Salmonella
      colonization/infection in chickens. Yet the mechanisms of probiotic effects are
      not fully understood. This study has characterized our previously-selected lactic
      acid-producing bacterial (LAB) isolates for controlling Salmonella infection in
      chickens, particularly the mechanism underlying the control.
      METHODOLOGY/PRINCIPAL FINDINGS: In vitro studies were conducted to characterize
      14 LAB isolates for their tolerance to low pH (2.0) and high bile salt (0.3-1.5%)
      and susceptibility to antibiotics. Three chicken infection trials were
      subsequently carried out to evaluate four of the isolates for reducing the burden
      of Salmonella enterica serovar Typhimurium in the broiler cecum. Chicks were
      gavaged with LAB cultures (10(6-7) CFU/chick) or phosphate-buffered saline (PBS)
      at 1 day of age followed by Salmonella challenge (10(4) CFU/chick) next day.
      Samples of cecal digesta, spleen, and liver were examined for Salmonella counts
      on days 1, 3, or 4 post-challenge. Salmonella in the cecum from Trial 3 was also
      assessed for the expression of ten virulence genes located in its pathogenicity
      island-1 (SPI-1). These genes play a role in Salmonella intestinal invasion.
      Tested LAB isolates (individuals or mixed cultures) were unable to lower
      Salmonella burden in the chicken cecum, but able to attenuate Salmonella
      infection in the spleen and liver. The LAB treatments also reduced almost all SPI
      1 virulence gene expression (9 out of 10) in the chicken cecum, particularly at
      the low dose. In vitro treatment with the extracellular culture fluid from a LAB
      culture also down-regulated most SPI-1 virulence gene expression.
      CONCLUSIONS/SIGNIFICANCE: The possible correlation between attenuation of
      Salmonella infection in the chicken spleen and liver and reduction of Salmonella
      SPI-1 virulence gene expression in the chicken cecum by LAB isolates is a new
      observation. Suppression of Salmonella virulence gene expression in vivo can be
      one of the strategies for controlling Salmonella infection in chickens.

PMID- 24728094
TI  - Hypoxia, blackwater and fish kills: experimental lethal oxygen thresholds in
      juvenile predatory lowland river fishes.
AB  - Hypoxia represents a growing threat to biodiversity in freshwater ecosystems.
      Here, aquatic surface respiration (ASR) and oxygen thresholds required for
      survival in freshwater and simulated blackwater are evaluated for four lowland
      river fishes native to the Murray-Darling Basin (MDB), Australia. Juvenile stages
      of predatory species including golden perch Macquaria ambigua, silver perch
      Bidyanus bidyanus, Murray cod Maccullochella peelii, and eel-tailed catfish
      Tandanus tandanus were exposed to experimental conditions of nitrogen-induced
      hypoxia in freshwater and hypoxic blackwater simulations using dried river red
      gum Eucalyptus camaldulensis leaf litter. Australia's largest freshwater fish, M.
      peelii, was the most sensitive to hypoxia but given that we evaluated tolerances
      of juveniles (0.99 +/- 0.04 g; mean mass +/-SE), the low tolerance of this
      species could not be attributed to its large maximum attainable body mass
      (>100,000 g). Concentrations of dissolved oxygen causing 50% mortality (LC50) in
      freshwater ranged from 0.25 +/- 0.06 mg l(-1) in T. tandanus to 1.58 +/- 0.01 mg
      l(-1) in M. peelii over 48 h at 25-26  degrees C. Logistic models predicted that
      first mortalities may start at oxygen concentrations ranging from 2.4 mg l(-1) to
      3.1 mg l(-1) in T. tandanus and M. peelii respectively within blackwater
      simulations. Aquatic surface respiration preceded mortality and this behaviour is
      documented here for the first time in juveniles of all four species. Despite the
      natural occurrence of hypoxia and blackwater events in lowland rivers of the MDB,
      juvenile stages of these large-bodied predators are vulnerable to mortality
      induced by low oxygen concentration and water chemistry changes associated with
      the decomposition of organic material. Given the extent of natural flow regime
      alteration and climate change predictions of rising temperatures and more severe
      drought and flooding, acute episodes of hypoxia may represent an underappreciated
      risk to riverine fish communities.

PMID- 24728096
TI  - The interrupted power law and the size of shadow banking.
AB  - Using public data (Forbes Global 2000) we show that the asset sizes for the
      largest global firms follow a Pareto distribution in an intermediate range, that
      is "interrupted" by a sharp cut-off in its upper tail, where it is totally
      dominated by financial firms. This flattening of the distribution contrasts with
      a large body of empirical literature which finds a Pareto distribution for firm
      sizes both across countries and over time. Pareto distributions are generally
      traced back to a mechanism of proportional random growth, based on a regime of
      constant returns to scale. This makes our findings of an "interrupted" Pareto
      distribution all the more puzzling, because we provide evidence that financial
      firms in our sample should operate in such a regime. We claim that the missing
      mass from the upper tail of the asset size distribution is a consequence of
      shadow banking activity and that it provides an (upper) estimate of the size of
      the shadow banking system. This estimate-which we propose as a shadow banking
      index-compares well with estimates of the Financial Stability Board until 2009,
      but it shows a sharper rise in shadow banking activity after 2010. Finally, we
      propose a proportional random growth model that reproduces the observed
      distribution, thereby providing a quantitative estimate of the intensity of
      shadow banking activity. 

PMID- 24728095
TI  - Ribosomal protein S29 regulates metabolic insecticide resistance through binding
      and degradation of CYP6N3.
AB  - BACKGROUND: Many diseases are transmitted by mosquitoes, including malaria,
      dengue fever, yellow fever, filariasis, and West Nile fever. Chemical control
      plays a major role in managing mosquito-borne diseases. However, excessive and
      continuous application of insecticides has caused the development of insecticide
      resistance in many species including mosquito, and this has become the major
      obstacle to controlling mosquito-borne diseases. Insecticide resistance is the
      result of complex polygenic inheritance, and the mechanisms are not well
      understood. Ribosomal protein RPS29 was found to be associated with DM resistance
      in our previous study. In this study, we aim to further investigate the
      involvement of RPS29 in deltamethrin resistance. METHODOLOGY AND PRINCIPAL
      FINDINGS: In this study, tandem affinity purification was used to identify
      proteins that can interact with RPS29. Among the candidate proteins, CYP6N3, a
      member of the CYP450 superfamily, was identified, and binding to RPS29 was
      confirmed in vitro and in vivo by GST pull-down and immunofluorescence. CCK-8
      assay was used to investigate the RPS29-CTP6N3 interaction in relation to DM
      resistance. CYP6N3 overexpression significantly enhanced DM resistance and insect
      cell viability, but this was reversed by RPS29 overexpression. Western blot was
      used to study the mechanism of interaction between RPS29 and CYP6N3. RPS29
      increases CYP6N3 protein degradation through the proteasome. CONCLUSIONS AND
      SIGNIFICANCE: These observations indicate that CYP6N3, a novel RPS29-interacting
      partner, could stimulate deltamethrin resistance in mosquito cells and RPS29
      overexpression targeted CYP6N3 for proteosomal degradation, abrogating the CYP6N3
      associated resistence to deltamethrin. Our findings provide a novel mechanism
      associated with CYP450s mediated DM resistance.

PMID- 24728098
TI  - Virtuous and vicious virtual water trade with application to Italy.
AB  - The current trade of agricultural goods, with connections involving all
      continents, entails for global exchanges of "virtual" water, i.e. water used in
      the production process of alimentary products, but not contained within. Each
      trade link translates into a corresponding virtual water trade, allowing
      quantification of import and export fluxes of virtual water. The assessment of
      the virtual water import for a given nation, compared to the national
      consumption, could give an approximate idea of the country's reliance on external
      resources from the food and the water resources point of view. A descriptive
      approach to the understanding of a nation's degree of dependency from overseas
      food and water resources is first proposed, and indices of water trade
      virtuosity, as opposed to inefficiency, are devised. Such indices are based on
      the concepts of self-sufficiency and relative export, computed systematically on
      all products from the FAOSTAT database, taking Italy as the first case study.
      Analysis of time series of the self-sufficiency and relative export can
      demonstrate effects of market tendencies and influence water-related policies at
      the international level. The goal of this approach is highlighting incongruent
      terms in the virtual water balances by the viewpoint of single products. Specific
      products, which are here referred to as "swap products", are in fact identified
      as those that lead to inefficiencies in the virtual water balance due to their
      contemporaneously high import and export. The inefficiencies due to the exchanges
      of the same products between two nations are calculated in terms of virtual water
      volumes. Furthermore, the cases of swap products are investigated by computing
      two further indexes denoting the ratio of virtual water exchanged in the swap and
      the ratio of the economic values of the swapped products. The analysis of these
      figures can help examine the reasons behind the swap phenomenon in trade. 

PMID- 24728097
TI  - Association between serum tissue inhibitor of matrix metalloproteinase-1 levels
      and mortality in patients with severe brain trauma injury.
AB  - OBJECTIVE: Matrix metalloproteinases (MMPs) and tissue inhibitors of matrix
      metalloproteinases (TIMPs) play a role in neuroinflammation after brain trauma
      injury (TBI). Previous studies with small sample size have reported higher
      circulating MMP-2 and MMP-9 levels in patients with TBI, but no association
      between those levels and mortality. Thus, the aim of this study was to determine
      whether serum TIMP-1 and MMP-9 levels are associated with mortality in patients
      with severe TBI. METHODS: This was a multicenter, observational and prospective
      study carried out in six Spanish Intensive Care Units. Patients with severe TBI
      defined as Glasgow Coma Scale (GCS) lower than 9 were included, while those with
      Injury Severity Score (ISS) in non-cranial aspects higher than 9 were excluded.
      Serum levels of TIMP-1, MMP-9 and tumor necrosis factor (TNF)-alpha, and plasma
      levels of tissue factor (TF) and plasminogen activator inhibitor (PAI)-1 plasma
      were measured in 100 patients with severe TBI at admission. Endpoint was 30-day
      mortality. RESULTS: Non-surviving TBI patients (n = 27) showed higher serum TIMP
      1 levels than survivor ones (n = 73). We did not find differences in MMP-9 serum
      levels. Logistic regression analysis showed that serum TIMP-1 levels were
      associated 30-day mortality (OR = 1.01; 95% CI = 1.001-1.013; P = 0.03). Survival
      analysis showed that patients with serum TIMP-1 higher than 220 ng/mL presented
      increased 30-day mortality than patients with lower levels (Chi-square = 5.50; P
      = 0.02). The area under the curve (AUC) for TIMP-1 as predictor of 30-day
      mortality was 0.73 (95% CI = 0.624-0.844; P<0.001). An association between TIMP-1
      levels and APACHE-II score, TNF- alpha and TF was found. CONCLUSIONS: The most
      relevant and new findings of our study, the largest series reporting data on TIMP
      1 and MMP-9 levels in patients with severe TBI, were that serum TIMP-1 levels
      were associated with TBI mortality and could be used as a prognostic biomarker of
      mortality in TBI patients.

PMID- 24728099
TI  - Climate driven life histories: the case of the Mediterranean storm petrel.
AB  - Seabirds are affected by changes in the marine ecosystem. The influence of
      climatic factors on marine food webs can be reflected in long-term seabird
      population changes. We modelled the survival and recruitment of the Mediterranean
      storm petrel (Hydrobates pelagicus melitensis) using a 21-year mark-recapture
      dataset involving almost 5000 birds. We demonstrated a strong influence of
      prebreeding climatic conditions on recruitment age and of rainfall and breeding
      period conditions on juvenile survival. The results suggest that the juvenile
      survival rate of the Mediterranean subspecies may not be negatively affected by
      the predicted features of climate change, i.e., warmer summers and lower
      rainfall. Based on considerations of winter conditions in different parts of the
      Mediterranean, we were able to draw inferences about the wintering areas of the
      species for the first time. 

PMID- 24728100
TI  - Grating-structured metallic microsprings.
AB  - We fabricate grating-structured metallic microsprings with well-defined helical
      angles and diameters, which are self-rolled from strained nanomembranes patterned
      with gratings. The grating structures on the metal membrane, replicated from the
      imprinted polymer layer beneath, give rise to the controlled rolling direction
      after selective etching of the underlying sacrificial layer. The rolling
      direction of the grating-structured thin metal film is always perpendicular to
      the long side edge of gratings, offering a good way to roll up strained strips
      into well controlled three-dimensional (3D) microsprings simply by altering the
      dimension and orientation of the structured strips. The mechanical elasticity of
      these grating-structured metallic microsprings is verified for the potential
      application as a flow rate sensor. Our work may stimulate rigorous synthesis of
      highly functional and complex 3D helical micro and nanostructures, and hint a
      broad range of applications such as environmental sensors, micro-/nanoscale
      robots, metamaterials, etc. 

PMID- 24728101
TI  - WISP-1 contributes to fractionated irradiation-induced radioresistance in
      esophageal carcinoma cell lines and mice.
AB  - Cancer cells that survive fractionated irradiation can be radioresistant and
      cause tumor recurrence. However, the molecular mechanisms underlying the
      development of radioresistance in cancer cells remain elusive. The aim of this
      study was to investigate the role of WISP-1 in the development of radioresistance
      in esophageal carcinoma during fractionated irradiation. Radioresistant
      esophageal cancer cells were generated from normal esophageal cancer cells via
      fractionated irradiation, and expression levels of related proteins were
      determined by Western blot. Radiosensitivity of cells was established by
      clonogenic cell survival assays, and cell cycle distribution was evaluated by
      flow cytometry. Protein distributions were determined by immunofluorescence, and
      cell toxicity was evaluated by cell counting kit-8 assays. In vivo validations
      were performed in a xenograft transplantation mouse model. Our data indicate that
      WISP-1 plays an important role in the development of radioresistance in
      esophageal cancer cells during fractionated irradiation. The overexression of
      WISP-1 in esophageal cancer cells was associated with radioresistance. Depletion
      of extracellular WISP-1 by antibody neutralizing reversed radioresistance and
      directly induced mitotic catastrophe resulting in cell death. WISP-1 may be a
      candidate therapeutic target in the treatment of recurrent esophageal carcinoma
      after radiotherapy. 

PMID- 24728102
TI  - IPF fibroblasts are desensitized to type I collagen matrix-induced cell death by
      suppressing low autophagy via aberrant Akt/mTOR kinases.
AB  - Idiopathic pulmonary fibrosis (IPF) is a chronic, lethal interstitial lung
      disease in which the aberrant PTEN/Akt axis plays a major role in conferring a
      survival phenotype in response to the cell death inducing properties of type I
      collagen matrix. The underlying mechanism by which IPF fibroblasts become
      desensitized to polymerized collagen, thereby eluding collagen matrix-induced
      cell death has not been fully elucidated. We hypothesized that the pathologically
      altered PTEN/Akt axis suppresses autophagy via high mTOR kinase activity, which
      subsequently desensitizes IPF fibroblasts to collagen matrix induced cell death.
      We found that the autophagosome marker LC3-2 expression is suppressed, while mTOR
      activity remains high when IPF fibroblasts are cultured on collagen. However, LC3
      2 expression increased in response to IPF fibroblast attachment to collagen in
      the presence of rapamycin. In addition, PTEN over-expression or Akt inhibition
      suppressed mTOR activity, thereby increasing LC3-2 expression in IPF fibroblasts.
      Furthermore, the treatment of IPF fibroblasts over-expressing PTEN or dominant
      negative Akt with autophagy inhibitors increased IPF fibroblast cell death.
      Enhanced p-mTOR expression along with low LC3-2 expression was also found in
      myofibroblasts within the fibroblastic foci from IPF patients. Our data show that
      the aberrant PTEN/Akt/mTOR axis desensitizes IPF fibroblasts from polymerized
      collagen driven stress by suppressing autophagic activity, which produces a
      viable IPF fibroblast phenotype on collagen. This suggests that the aberrantly
      regulated autophagic pathway may play an important role in maintaining a
      pathological IPF fibroblast phenotype in response to collagen rich environment. 

PMID- 24728103
TI  - Out-of-pocket payments, health care access and utilisation in south-eastern
      Nigeria: a gender perspective.
AB  - Out-of-pocket (OOP) payments have severe consequences for health care access and
      utilisation and are especially catastrophic for the poor. Although women comprise
      the majority of the poor in Nigeria and globally, the implications of OOP
      payments for health care access from a gender perspective have received little
      attention. This study seeks to fill this gap by using a combination of
      quantitative and qualitative analysis to investigate the gendered impact of OOPs
      on healthcare utilisation in south-eastern Nigeria. 411 households were surveyed
      and six single-sex Focus Group Discussions conducted. This study confirmed the
      socioeconomic and demographic vulnerability of female-headed households (FHHs),
      which contributed to gender-based inter-household differences in healthcare
      access, cost burden, choices of healthcare providers, methods of funding
      healthcare and coping strategies. FHHs had higher cost burdens from seeking care
      and untreated morbidity than male-headed households (MHHs) with affordability as
      a reason for not seeking care. There is also a high utilisation of patent
      medicine vendors (PMVs) by both households (PMVs are drug vendors that are
      unregulated, likely to offer very low-quality treatment and do not have trained
      personnel). OOP payment was predominantly the means of healthcare payment for
      both households, and households spoke of the difficulties associated with
      repaying health-related debt with implications for the medical poverty trap. It
      is recommended that the removal of user fees, introduction of prepayment schemes,
      and regulating PMVs be considered to improve access and provide protection
      against debt for FHHs and MHHs. The vulnerability of widows is of special concern
      and efforts to improve their healthcare access and broader efforts to empower
      should be encouraged for them and other poor households. 

PMID- 24728104
TI  - Transperineal versus transvaginal ultrasound cervical length measurement and
      preterm labor.
AB  - OBJECTIVE: The aim was to evaluate the agreement between and the reproducibility
      of transperineal and transvaginal ultrasound cervical length measurements
      performed by the duty obstetrical team in case of preterm labor. The
      acceptability of transperineal ultrasonography was also assessed. METHODS:
      Pregnant patients between 25 and 34 weeks of gestation with contractions and a
      clinically modified cervix were included. Order of ultrasonography examination
      (transperineal or transvaginal first) and rank of operator (resident or senior)
      were allocated randomly. Agreement was assessed using the intraclass correlation
      coefficient (ICC) and the Bland and Altman plot. The patient's discomfort and
      preference for either method were assessed with a questionnaire. RESULTS: 62
      patients admitted for preterm labor between 25 and 34 weeks of gestation were
      included. Six seniors and nine residents took part in the study. Among the 51
      patients with an interpretable transperineal ultrasound scan, median cervical
      length measurements with the transperineal and the transvaginal technique were,
      respectively, 25 mm (0-53) and 27 mm (4-51). Concordance was good with an ICC of
      0.83 [IC 95 % = (0.73-0.90)]. Transperineal ultrasonography was preferred in 56.5
      % of cases. CONCLUSION: In case of preterm labor, cervical length measurement
      with transperineal ultrasonography seems reproducible and can be performed by the
      obstetric team on duty.

PMID- 24728105
TI  - Morphological and immunohistochemical analysis in ovaries and fallopian tubes of
      tamoxifen, letrozole and clomiphene-treated rats.
AB  - PURPOSE: Ovarian and tubal dysplasia may be precursors to ovarian cancer. The
      goal of this study was to check whether these histopathological lesions would be
      found after ovulation induction using tamoxifen, clomiphene citrate and
      letrozole. METHODS: Seventy-two rats were divided into four groups. In the first
      group, 24 rats received normal saline. The second group (16 rats) received
      clomiphene citrate for six cycles. The third group, divided into two sub-groups
      of eight rats each, were stimulated with tamoxifen for six cycles, with a dosage,
      respectively, of 0.4 and 0.8 mg/kg/day. In the last group, eight rats received
      letrozole 0.1 mg/kg/day and eight other rats received letrozole 0.5 mg/kg/day,
      for six cycles. Once the six cycles had been completed the rats were killed in
      order to remove ovaries and tubes for histopathological analysis (morphological,
      p53 and Ki67 immunohistochemical assessment). RESULTS: Histopathological lesions
      were found in both ovaries and tubes. The mean ovarian dysplasia score was
      significantly higher in the tamoxifen group whatever the dosage (p = 0.006 and
      0.0002) and in the letrozole group with 0.5 mg/kg/day (p = 0.0002) compared with
      the control group. The mean tubal dysplasia score was significantly higher in all
      groups that received drug treatment compared with the control group, whatever the
      dosage used. The proliferation index (Ki67) was significantly higher in the
      tamoxifen and letrozole groups while no significant difference was found for
      apoptosis marker p53. CONCLUSIONS: Ovulation induction may induce
      histopathological abnormalities in ovaries and tubes with a different
      immunohistochemical profile in comparison with salpingo-oophorectomies for
      genetic risk.

PMID- 24728106
TI  - The association between gestational weight gain and substantial weight retention
      1-year postpartum.
AB  - PURPOSE: Postpartum weight retention contributes to obesity development of women
      in their reproductive age. The studies about the association between gestational
      weight gain (GWG) and substantial weight retention are lacking. This study
      examined the association between GWG and substantial postpartum weight retention
      (SPPWR). METHODS: The participants (n = 1,122) in the study were healthy, mature
      and fed their infants whose ages were 3, 6, 9, 12 months (2010-2012),
      respectively. They self-reported their socio-demographic, clinical prenatal and
      behaviors characteristics via questionnaires. We collected their weight data
      including pre-pregnancy and prior to delivery, as well as weight at 3, 6, 9, and
      12 months postpartum. The major outcomes included weight retention and
      substantial weight gain 1 year postpartum. RESULTS: Of the 1,122 women, the
      median weight retention was 3.0 (IQR = 5.5) kg 12 months postpartum. 35.7 % of
      them reported substantial weight retention (>=4.55 kg). GWG categories were
      established as follows: inadequate weight gain (n = 366, 33 %), adequate weight
      gain (n = 596, 53 %), and excessive weight gain (n = 160, 14 %). Adjusted odds
      ratios of SPPWR were 0.59 (95 % CI 0.43, 0.81) for inadequate weight gain and
      4.05 (95 % CI 2.75, 5.95) for excessive weight gain versus adequate weight gain
      (P < 0.001). CONCLUSIONS: Excessive GWG would increase the risk of substantial
      weight retention 1-year postpartum. The interventions to prevent postpartum
      obesity should consider the strategies how to attain optimal maternal GWG.

PMID- 24728107
TI  - Is uterine myomectomy a safe option during cesarean section?

PMID- 24728109
TI  - Blame, Shame, and Lack of Support: A Multilevel Study on Obesity Management.
AB  - In this research, we examined the experiences of individuals living with obesity,
      the perceptions of health care providers, and the role of social, institutional,
      and political structures in the management of obesity. We used feminist
      poststructuralism as the guiding methodology because it questions everyday
      practices that many of us take for granted. We identified three key themes across
      the three participant groups: blame as a devastating relation of power, tensions
      in obesity management and prevention, and the prevailing medical management
      discourse. Our findings add to a growing body of literature that challenges a
      number of widely held assumptions about obesity within a health care system that
      is currently unsupportive of individuals living with obesity. Our identification
      of these three themes is an important finding in obesity management given the
      diversity of perspectives across the three groups and the tensions arising among
      them.

PMID- 24728110
TI  - Experiencing Wellness Within Illness: Exploring a Mindfulness-Based Approach to
      Chronic Back Pain.
AB  - In this article I explore how mindfulness-based techniques affect perceptions and
      management of back pain and discuss these findings in relation to embodiment
      theory and liminality. Sixteen volunteers attending Breathworks for persistent
      back pain took part in this study. The theme of "embodied awareness" formed the
      core category, as all participants reported a change in their experience of pain.
      Such embodied changes are described in relation to five subthemes: unpacking the
      pain experience, changing relationship to pain, letting go of the label, self
      compassion and acceptance, and wellness within illness. Learning to respond
      rather than react, and living moment by moment enabled participants to replace a
      cycle of suffering with one of acceptance. Rather than fearing pain, participants
      found ways to move through it and live with it. Although some expressed finding a
      sense of wellness despite ongoing pain, all participants reported greater
      acceptance and a better quality of life.

PMID- 24728108
TI  - Designing of promiscuous inhibitors against pancreatic cancer cell lines.
AB  - Pancreatic cancer remains the most devastating disease with worst prognosis.
      There is a pressing need to accelerate the drug discovery process to identify new
      effective drug candidates against pancreatic cancer. We have developed QSAR
      models for predicting promiscuous inhibitors using the pharmacological data. Our
      models achieved maximum Pearson correlation coefficient of 0.86, when evaluated
      on 10-fold cross-validation. Our models have also successfully validated the drug
      to-oncogene relationship and further we used these models to screen FDA approved
      drugs and tested them in vitro. We have integrated these models in a webserver
      named as DiPCell, which will be useful for screening and designing novel
      promiscuous drug molecules. We have also identified the most and least effective
      drugs for pancreatic cancer cell lines. On the other side, we have identified
      resistant pancreatic cancer cell lines, which need investigative scanner on them
      to put light on resistant mechanism in pancreatic cancer. 

PMID- 24728111
TI  - Exploring women's experiences of health and well-being in remote northwest
      Queensland, Australia.
AB  - Rural and remote environments are challenging places in which to achieve health
      and well-being. In this woman-centered, grounded theory study, I explored the
      meaning of health and well-being as well as how it is achieved from the
      perspective of women living in remote inland parts of Australia. The study was
      based on semistructured interviews with 23 women living in geographically remote
      areas. The findings are presented as a model of the capacity to flourish.
      Flourishing describes an optimal achievable state of well-being, delineated by
      four interrelated dimensions of experience: control, connecting, belonging, and
      identity. I identify individual, contextual, and structural factors that enable
      and constrain the capacity to flourish. The findings suggest that approaches to
      understanding and promoting women's health in remote areas should be more
      holistic and contextual. 

PMID- 24728112
TI  - Transposon based activation tagging in diploid strawberry and monoploid
      derivatives of potato.
AB  - KEY MESSAGE: Diploid strawberry and potato transformed with a transposon tagging
      construct exhibited either global (strawberry) or local transposition (potato).
      An activation tagged, compact-sized strawberry mutant overexpressed the gene
      adjacent to Ds. As major fruit and vegetable crops, respectively, strawberry and
      potato are among the first horticultural crops with draft genome sequences. To
      study gene function, we examined transposon-tagged mutant strategies in model
      populations for both species, Fragaria vesca and Solanum tuberosum Group Phureja,
      using the same Activation/Dissociation (Ac/Ds) construct. Early somatic
      transposition during tissue culture occurred at a frequency of 18.5% in
      strawberry but not in potato transformants. Green fluorescent protein under a
      monocot promoter was a more reliable selectable marker in strawberry compared to
      potato. BASTA (gluphosinate herbicide) resistance served as an effective
      selectable marker for both species (80 and 85% reliable in strawberry and potato,
      respectively), although the effective concentration differed (0.5% for strawberry
      and 0.03% for potato). Transposons preferentially reinserted within genes (exons
      and introns) in both species. Real-time quantitative PCR revealed enhanced gene
      expression (670 and 298-fold expression compared to wild type in petiole and leaf
      tissue, respectively) for an activation tagged strawberry mutant with Ds inserted
      about 0.6 kb upstream from a gene coding for an epidermis-specific secreted
      glycoprotein EP1. Our data also suggested that endopolyploid (diploid) cells
      occurring in leaf explants of monoploid potato were the favored targets of T-DNA
      integration during transformation. Mutants obtained in these studies provide a
      useful resource for future genetic studies.

PMID- 24728114
TI  - [Not Available].

PMID- 24728113
TI  - Arabidopsis HRE1alpha, a splicing variant of AtERF73/HRE1, functions as a nuclear
      transcription activator in hypoxia response and root development.
AB  - KEY MESSAGE: HRE1alpha shows transcriptional activation activity in its C
      terminal region via GCC box but not DRE/CRT and plays an important role in root
      development via root meristem cell division regulation. AtERF73/HRE1 protein, a
      member of the Arabidopsis AP2/ERF family, contains a conserved AP2/ERF DNA
      binding domain. Here, we studied the molecular function of HRE1alpha, a splicing
      variant of AtERF73/HRE1, as well as its role in root development. HRE1alpha
      overexpressing transgenic plants (OXs) showed tolerance to submergence. HRE1alpha
      showed transcriptional activation activity via GCC box but not DRE/CRT. The 121
      211 aa region of HRE1alpha was responsible for the transcriptional activation
      activity, and the region was conserved among homologs of other species but was
      not found in other Arabidopsis proteins. HRE1alpha OXs showed increased primary
      root length due to elevated root cell division. Our results suggest that
      HRE1alpha functions as a transcription activator in the nucleus, and plays an
      important role in root development through regulation of root meristem cell
      division.

PMID- 24728115
TI  - [Not Available].
AB  - Rheumatoid Arthritis is a progressive and systemic inflammatory disorder of
      unknown etiology that frequently leads to joint destruction accompanied by multi
      system extra-articular manifestations. No curative therapy is available today.
      Compared to usual Disease Modifying Antirheumatic Drugs (DMARDs), biologicals
      such as tumor necrosis factor (TNF) alpha- and interleukin (IL) 1-inhibitors
      appear to offer greater efficacy and safety, especially in refractory cases. This
      article deals with the new agents infliximab, etanercept, and anakinra as well as
      with additional newly developed cytokine-inhibitors. In order to control their
      use and possible unknown long-term effects, a network of international and
      national committees has been installed. The actual recommendations for the
      treatment of rheumatoid arthritis with biologicals are presented, and the cost
      benefit relation is discussed. 

PMID- 24728116
TI  - [Not Available].
AB  - Ankylosing spondylitis (AS) and psoriatic arthritis (PsA) are common inflammatory
      rheumatic diseases who belong to the spectrum of the spondyloarthritides (SpA).
      The therapeutic options for these conditions have been rather limited in the past
      decades. Standard treatment consists of drug therapy with nonsteroidal anti
      inflammatory agents (NSAIDs), intraarticular steroids and physiotherapy. The
      peripheral symptoms of SpA respond partly to treament with disease modifying anti
      rheumatic drugs (DMARDs). Several findings of the last years have indicated that
      TNFalpha plays a role in the pathogenesis of the SpA. Treatment with TNFalpha
      antagonists (monoclonal antibodies and receptor fusion proteins directed against
      TNFalpha) have been successfully used in patients with rheumatoid arthritis (RA),
      a pathogenetically distinct form of chronic joint inflammation. After stimulating
      pilot studies there is now increasing evidence from randomized controlled trials
      that these antagonists are very efficacious in the treatment of SpA, especially
      of AS and PsA, for both, axial and peripheral symptoms of disease. This therapy
      seems to be even more effective in SpA than in RA being comparable to the
      efficacy of corticosteroid therapy for polymyalgia rheumatica. There is
      international consensus that the availabilitiy of TNFalpha antagonists is a major
      breakthrough in the therapy of rheumatic diseases. 

PMID- 24728117
TI  - [Not Available].
AB  - Juvenile idiopathic arthritis is a chronic inflammatory disease with uncertain
      outcome. Patients may suffer from severe joint damage leading to mutilations as
      well as from extra-articular manifestations. Prognosis is variable and depends in
      part on the number of affected joints and the occurrence of extra-articular
      manifestations. Treatment regimes should take this into account. Pharmacomedical
      treatment strategies include the application of nonsteroidal antirheumatics,
      corticosteroids, sulfasalazine, and immunosuppressive substances. However, of the
      latter only methotrexate has been shown in controlled trials to be effective.
      Other immunosuppressive drugs such as azathioprine, cyclosporine A, and
      leflunomide have not yet been investigated sufficiently. In addition, there is no
      scientific basis for the application of gold salts or (hydroxy)chloroquine. New
      therapeutic biologic agents, notably the tumor necrosis factor inhibitors, have
      achieved dramatic improvements also in patients with severe, as yet intractable
      disease. However, until now randomized, placebo-controlled trials have been
      performed for etanercept only. Dramatic improvement was accompanied by low
      toxicity. Infections as well as the development of autoimmune diseases have been
      shown to be the major potential side effects. Long-term toxicity still has to be
      evaluated. Treatment with other biopharmaceuticals such as infliximab, IL-1Ra,
      anti-IL-6 receptor antibodies, and further cytokine antagonists remains
      experimental. 

PMID- 24728118
TI  - [Not Available].
AB  - Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used to treat pain and
      inflammation in osteoarthritis and rheumatoid arthritis. However, their long-term
      use is often limited by gastrointestinal mucosal injury and complications like
      bleeding, ulceration and perforation. Hence, the hope evolved that selective COX
      2 inhibitors, a newly developed class of anti-inflammatory drugs, may be equally
      effective but better tolerated than nonselective NSAIDs. However, this enthusiasm
      was partly dampened by the fact that the exclusive use of selective COX-2
      inhibitors is probably not justified. Particularly in patients treated with low
      dose of aspirin for cardiovascular prophylaxis, the COX-2 inhibitors seem to have
      no obvious advantages over conventional NSAIDs. Furthermore, use of COX-2
      inhibitors has recently been associated with enhanced cardiovascular risk. There
      is some evidence that COX-2 inhibitors may act via COX independent pathways and
      might be used for indications other than arthritic pain and inflammation. 

PMID- 24728119
TI  - [Not Available].
AB  - Multiple studies in osteoarthritis (OA), rheumatoid arthritis (RA), and several
      acute pain models indicate that the cyclooxygenase-2-specific inhibitors
      celecoxib and rofecoxib are equally effective as the conventional nonsteroidal
      antirheumatic drugs diclofenac, ibuprofen, and naproxen. Both drugs are approved
      for the treatment of OA and RA in a daily dosage of 2*100 mg, 1*200 mg, and 2*200
      mg (celecoxib) or 1*12.5 mg and 1*25 mg (rofecoxib). In addition, rofecoxib has
      also been approved by the FDA for the treatment of postsurgical pain in a dosage
      of 50 mg. Normally celecoxib is used in a dosage of 1*200 mg for OA and 2*200 mg
      for RA, whereas both 12.5 and 25 mg rofecoxib are used for the treatment of OA
      and 25 mg for the treatment of RA. Coxibs might also be used for the treatment of
      seronegative spondarthritides, as is indicated by a successful study using
      celecoxib for the treatment of ankylosing spondylitis. 

PMID- 24728120
TI  - [Not Available].
AB  - On the basis of relevant clinical studies performed so far, selective COX-2
      inhibitors exhibit a therapeutic advantage over conventional NSAIDs with regard
      to the incidence of gastrointestinal (GI) damage such as perforation, ulceration,
      and bleeding (PUBs). The results prove that a risk reduction could be
      demonstrated during long-term treatment (6-9 months); nevertheless, PUBs cannot
      be ruled out under treatment with selective COX-2 inhibitors. In contrast to
      this, dyspeptic symptoms occur very frequently and their incidence is comparable
      to that of conventional NSAIDs. The increased incidence of thromboembolic,
      cardiovascular events documented in the VIGOR study for rofecoxib versus naproxen
      was not confirmed by comparison to placebo and other NSAIDs in additional
      clinical studies. In clinical studies no clear signs of thrombotic effects have
      been described for the therapeutic administration of celecoxib. Based on
      preclinical investigations as well as on the thromboembolic, cardiovascular
      events reported in connection with the therapeutic use of COX-2 inhibitors,
      safety measures are necessary and further investigations are recommended. 

PMID- 24728121
TI  - [Not Available].
AB  - Intestinal infections in Germany due to enterohemorrhagic E. coli bacteria (EHEC)
      between 1998 and 2001 reveal a large scale of biological diversity of their
      pathogens. However, no dramatic increase of their clinical importance and public
      health implications has been observed. As strains of serovar O157:H7 have
      continuously declined as causative agents, other serovars such as O26:H11 and
      O103:H2 have replaced them. The great diversity of the EHEC pathogens might point
      to a great number of various infection routes and sources. Since recently new
      pathogenic factors of EHEC bacteria have been detected (especially by the
      sequencing of the genome of EHEC), it is currently not possible to define a clear
      cut difference between human pathogens and nonhuman pathogens. The enhanced
      surveillance of EHEC pathogens with respect to their biological diversity and
      dynamics, their epidemic spread, and their infection routes and sources remain an
      essential task of the public health authorities. 

PMID- 24728122
TI  - [Not Available].

PMID- 24728123
TI  - [Not Available].

PMID- 24728124
TI  - The novel bladder preservation therapy BOAI-CDDP-radiation (OMC-regimen): a new
      treatment option for invasive bladder cancer patients with lymph node metastasis.
AB  - We have developed a novel bladder preservation therapy for patients with muscle
      invasive bladder cancer and lymph node metastasis: balloon-occluded arterial
      infusion (BOAI) of cisplatin/gemcitabine, with concomitant hemodialysis and
      irradiation [the so-called 'OMC (Osaka Medical College) regimen']. The OMC
      regimen delivers an extremely high concentration of anticancer agent to the site
      of the tumor, as well as the pelvic area, without causing any adverse systemic
      effects. In this study, we investigated the efficiency of the OMC regimen in 34
      patients who underwent BOAI with cisplatin (100, 200 or 300 mg) along with 60 Gy
      of irradiation; patients who failed to achieve CR underwent secondary BOAI with
      gemcitabine (1,600 mg). The overall clinical response was 73.5% (CR: 35.3%; PR:
      17.6%; SD: 20.6%). The 5-year overall and progression-free survival rates were
      54.4% and 52.5%, respectively. For treatment failure, N2 stage was selected as a
      significant risk factor by simple and multiple logistic regression analyses. Cox
      proportional hazards analyses showed that N2 stage, T4 stage and the presence of
      hydronephrosis were significant risk factors for overall survival. Indeed, 55.6%
      of patients with N1 stage achieved a complete response (CR) (vs. 12.5% for N2
      patients, p=0.0151), and 90% (9/10) of the CR patients survived without
      recurrence with an intact bladder after a mean follow-up of 85 (range 7-193)
      weeks. The 3-year progrssion-free survival rate with an intact bladder was 65.8%
      (vs. 37.5% for N2, p=0.034), and the 5-year overall survival rate was 71.8% (vs.
      30.6% for N2, p=0.004). No patients suffered severe toxicities of Grade II or
      more; the oldest patient, aged 85 years, successfully completed this therapy. In
      conclusion, the OMC regimen can be regarded as a new option for patients with
      macroscopic lymph node involvement, especially those at stage N1. Therapy will
      improve the feasibility of radical cure even without the need for cystectomy in
      patients for whom surgery after neoadjuvant chemotherapy would otherwise be
      necessary, and also facilitate potential cure in patients for whom, otherwise,
      merely palliative treatment would seem the only option. 

PMID- 24728125
TI  - Communication architecture for AAL. Supporting patient care by health care
      providers in AAL-enhanced living quarters.
AB  - INTRODUCTION: This article is part of the Focus Theme of Methods of Information
      in Medicine on "Using Data from Ambient Assisted Living and Smart Homes in
      Electronic Health Records". BACKGROUND: Concepts of Ambient Assisted Living (AAL)
      support a long-term health monitoring and further medical and other services for
      multi-morbid patients with chronic diseases. In Germany many AAL and telemedical
      applications exist. Synergy effects by common agreements for essential
      application components and standards are not achieved. OBJECTIVES: It is
      necessary to define a communication architecture which is based on common
      definitions of communication scenarios, application components and communication
      standards. METHODS: The development of a communication architecture requires
      different steps. To gain a reference model for the problem area different AAL and
      telemedicine projects were compared and relevant data elements were generalized.
      The derived reference model defines standardized communication links. RESULTS: As
      a result the authors present an approach towards a reference architecture for AAL
      communication. The focus of the architecture lays on the communication layer. The
      necessary application components are identified and a communication based on
      standards and their extensions is highlighted. CONCLUSION: The exchange of
      patient individual events supported by an event classification model, raw and
      aggregated data from the personal home area over a telemedicine center to health
      care providers is possible.

PMID- 24728126
TI  - Synthesis and derivatization of highly-functionalized lambda5-phospholes.
AB  - A variety of lambda(5)-phosphole derivatives bearing up to three distinct
      peripheral functionalities have been prepared by regiospecific [3+2]
      cycloaddition reactions of the diphosphinoketenimine (PPh2)2C=C=NtBu (1) with
      electron-poor alkenes. Selective derivatization of the exocyclic functional
      groups, including formation of dimetallic complexes with a phosphole core, was
      subsequently accomplished.

PMID- 24728127
TI  - Common genetic variation in the glucokinase gene (GCK) is associated with type 2
      diabetes and rates of carbohydrate oxidation and energy expenditure.
AB  - AIMS/HYPOTHESIS: Glucokinase (GCK) plays a role in glucose metabolism and glucose
      stimulated insulin secretion. Rare mutations in GCK cause MODY. We investigated
      whether common variation (minor allele frequency >=0.01) in GCK is associated
      with metabolic traits and type 2 diabetes. METHODS: Four exonic single-nucleotide
      polymorphisms (SNPs) and three SNPs predicted to cause loss of promoter function
      were identified in whole-genome sequence data from 234 Pima Indians. These seven
      tag SNPs and rs4607517, a type 2 diabetes variant established in other studies,
      were analysed in 415 full-heritage non-diabetic Pima Indians characterised for
      metabolic traits, and 7,667 American Indians who had data on type 2 diabetes and
      BMI. RESULTS: A novel 3' untranslated region (3'UTR) SNP, chr7:44184184-G/A, was
      associated with the rate of carbohydrate oxidation post-absorptively (beta = 0.22
      mg [kg estimated metabolic body size (EMBS)](-1) min(-1), p = 0.005) and during a
      hyperinsulinaemic-euglycaemic clamp (beta = 0.24 mg [kg EMBS](-1) min(-1), p =
      0.0002), the rate of carbohydrate oxidation in a respiratory chamber (beta = 311
      kJ/day, p = 0.03) and 24 h energy expenditure, which was attributable to the
      thermic effect of food (beta = 520 kJ/day, p = 3.39 * 10(-6)). This 3'UTR SNP was
      also associated with diabetes (OR 1.36, 95% CI 1.11, 1.65, p = 0.002), where the
      A allele (allele frequency 0.05) was associated with a lower rate of carbohydrate
      oxidation, lower 24 h energy expenditure and higher risk for diabetes. In a Cox
      proportional hazards model, a rate of insulin-stimulated carbohydrate oxidation
      lower than the mean rate at baseline predicted a higher risk for developing
      diabetes than for those above the mean (hazard rate ratio 2.2, 95% CI 1.3, 3.6, p
      = 0.002). CONCLUSIONS/INTERPRETATION: Common variation in GCK influences the rate
      of carbohydrate oxidation, 24 h energy expenditure and diabetes risk in Pima
      Indians.

PMID- 24728129
TI  - Whether coordinative (soccer) exercise improves executive functioning in
      kindergarten children has yet to be demonstrated.

PMID- 24728128
TI  - Genetic variation in MTNR1B is associated with gestational diabetes mellitus and
      contributes only to the absolute level of beta cell compensation in Mexican
      Americans.
AB  - AIMS/HYPOTHESIS: MTNR1B is a type 2 diabetes susceptibility locus associated with
      cross-sectional measures of insulin secretion. We hypothesised that variation in
      MTNR1B contributes to the absolute level of a diabetes-related trait, temporal
      rate of change in that trait, or both. METHODS: We tested rs10830963 for
      association with cross-sectional diabetes-related traits in up to 1,383
      individuals or with rate of change in the same phenotypes over a 3-5 year follow
      up in up to 374 individuals from the family-based BetaGene study of Mexican
      Americans. RESULTS: rs10830963 was associated cross-sectionally with fasting
      glucose (p = 0.0069), acute insulin response (AIR; p = 0.0013), disposition index
      (p = 0.00078), glucose effectiveness (p = 0.018) and gestational diabetes
      mellitus (OR 1.48; p = 0.012), but not with OGTT 30 min Deltainsulin (the
      difference between the 30 min and fasting plasma insulin concentration) or 30 min
      insulin-based disposition index. rs10830963 was also associated with rate of
      change in fasting glucose (p = 0.043), OGTT 30 min Deltainsulin (p = 0.01) and
      AIR (p = 0.037). There was no evidence for an association with the rate of change
      in beta cell compensation for insulin resistance. CONCLUSIONS/INTERPRETATION: We
      conclude that variation in MTNR1B contributes to the absolute level of insulin
      secretion but not to differences in the temporal rate of change in insulin
      secretion. The observed association with the rate of change in insulin secretion
      reflects the natural physiological response to changes in underlying insulin
      sensitivity and is not a direct effect of the variant.

PMID- 24728130
TI  - Response interference in touch, vision, and crossmodally: beyond the spatial
      dimension.
AB  - To date, tactile distractor processing has primarily been investigated by
      focusing on the spatial characteristics of distractors and the impact of their
      presentation on the orienting of attention. In two experiments, we examined the
      influence of tactile distractors when the location of stimulus presentation was
      kept constant, thus controlling for the effects of spatial attention. A response
      priming paradigm was used in which two stimuli were sequentially presented from
      the same (fixated) direction. Typically, target responses are facilitated when
      the previously presented distractor (i.e., the prime) happens to map on to the
      same response as compared to the distractor maps on to the opposite response.
      Similar response priming effects were observed for tactile and visual distractors
      within a unimodal experimental setting (Experiments 1a and 1b). Interestingly,
      however, when the targets and distractors were presented in different sensory
      modalities, only the visual distractors exerted a crossmodal effect on the
      subsequent processing of vibrotactile targets (Experiment 2). These results
      therefore indicate that visual stimuli automatically trigger their corresponding
      response even when the task at hand is not visual, whereas tactile stimuli are
      only processed up to the level of response generation when the participants' task
      is tactile. 

PMID- 24728132
TI  - Cell directional spread determines accuracy, precision, and length of the
      neuronal population vector.
AB  - The neuronal population vector (NPV) for movement direction is the sum of
      weighted neuronal directional contributions. Based on theoretical considerations,
      we proposed recently that the sharpness of tuning will impact the directional
      precision, accuracy, and length of the NPV, such that sharper tuning will yield
      NPV with higher precision, higher accuracy, and shorter length (Mahan and
      Georgopoulos in Front Neural Circuits 7:92, 2013). Furthermore, we proposed that
      controlling the inhibitory drive in a local network could be the mechanism by
      which the sharpness of directional tuning would be varied, resulting in a
      continuous specification and control of movement's directional precision,
      accuracy, and speed (Mahan and Georgopoulos in Front Neural Circuits 7:92, 2013,
      Fig. 5). As a first step in testing this idea, here we analyzed data from 899
      cells recorded in the motor cortex during performance of a center -> out task.
      There were two major findings. First, directional selectivity varied with cell
      activity, such that it was higher in cells with lower mean discharge rates. And
      second, NPVs calculated from subsets of cells with higher directional selectivity
      (and, correspondingly, lower mean discharge rates) were more accurate (i.e.,
      closer to the movement), precise (i.e., less variable), and shorter (i.e.,
      slower; Schwartz in Science 265:540-542, 1994). These findings confirm our
      predictions above made from modeling (Mahan and Georgopoulos in Front Neural
      Circuits 7:92, 2013) and provide a simple mechanism by which desired attributes
      of the directional motor command can be implemented. We hypothesize that the
      inhibitory drive in a local network is controlled directly and independently of
      recurrent collaterals or common excitatory inputs to other cells. This could be
      achieved by a private excitation/inhibition of key inhibitory interneurons in a
      way similar to that in operation for Renshaw cells in the spinal cord. The
      presence of such a private line of inhibitory control remains to be investigated.

PMID- 24728131
TI  - Understanding individual face discrimination by means of fast periodic visual
      stimulation.
AB  - This paper reviews a fast periodic visual stimulation (FPVS) approach developed
      recently to make significant progress in understanding visual discrimination of
      individual faces. Displaying pictures of faces at a periodic frequency rate leads
      to a high signal-to-noise ratio (SNR) response in the human electroencephalogram,
      at the exact frequency of stimulation, a so-called steady-state visual evoked
      potential (SSVEP, Regan in Electroencephalogr Clin Neurophysiol 20:238-248,
      1966). For fast periodic frequency rates, i.e., between 3 and 9 Hz, this response
      is reduced if the exact same face identity is repeated compared to the
      presentation of different face identities, the largest difference being observed
      over the right occipito-temporal cortex. A 6-Hz stimulation rate (cycle duration
      of ~170 ms) provides the largest difference between different and repeated faces,
      as also evidenced in face-selective areas of the ventral occipito-temporal cortex
      in functional magnetic resonance imaging. This high-level discrimination response
      is reduced following inversion and contrast-reversal of the faces and can be
      isolated without subtraction thanks to a fast periodic oddball paradigm. Overall,
      FPVS provides a response that is objective (i.e., at an experimentally defined
      frequency), implicit, has a high SNR and is directly quantifiable in a short
      amount of time. Although the approach is particularly appealing for understanding
      face perception, it can be generalized to study visual discrimination of complex
      visual patterns such as objects and visual scenes. The advantages of the approach
      make it also particularly well-suited to investigate these functions in
      populations who cannot provide overt behavioral responses and can only be tested
      for short durations, such as infants, young children and clinical populations.

PMID- 24728133
TI  - Quantitative analysis of dynamic association in live biological fluorescent
      samples.
AB  - Determining vesicle localization and association in live microscopy may be
      challenging due to non-simultaneous imaging of rapidly moving objects with two
      excitation channels. Besides errors due to movement of objects, imaging may also
      introduce shifting between the image channels, and traditional colocalization
      methods cannot handle such situations. Our approach to quantifying the
      association between tagged proteins is to use an object-based method where the
      exact match of object locations is not assumed. Point-pattern matching provides a
      measure of correspondence between two point-sets under various changes between
      the sets. Thus, it can be used for robust quantitative analysis of vesicle
      association between image channels. Results for a large set of synthetic images
      shows that the novel association method based on point-pattern matching
      demonstrates robust capability to detect association of closely located vesicles
      in live cell-microscopy where traditional colocalization methods fail to produce
      results. In addition, the method outperforms compared Iterated Closest Points
      registration method. Results for fixed and live experimental data shows the
      association method to perform comparably to traditional methods in colocalization
      studies for fixed cells and to perform favorably in association studies for live
      cells. 

PMID- 24728136
TI  - The epidemiology of eating disorders: genetic, environmental, and societal
      factors.
AB  - BACKGROUND: The aim of this review was to summarize the literature to date
      regarding the sociodemographic, environmental, and genetic correlates of eating
      disorders (EDs) in adults. METHOD: A keyword search was entered into Scopus
      (SciVerse, Elsevier) to identify relevant articles published in English up until
      June 2013. Articles were assessed against a range of a priori inclusion and
      exclusion criteria. RESULTS: A total of 149 full-text articles were found to be
      eligible for the review and included 86 articles with data on sociodemographic
      correlates, 57 on environmental correlates, and 13 on genetic correlates. Female
      sex, younger age, sexual and physical abuse, participation in esthetic or weight
      oriented sports, and heritability were found to be most consistently associated
      with higher ED prevalence and incidence. Conversely, ethnicity, socioeconomic
      status, education, and urbanicity did not appear to have strong associations with
      ED epidemiology. CONCLUSION: More community-based research, with an equal
      representation of males, needs to be conducted to confirm the current findings
      and provide evidence for emerging factors that may be related to EDs.

PMID- 24728135
TI  - Polycomb proteins control proliferation and transformation independently of cell
      cycle checkpoints by regulating DNA replication.
AB  - The ability of PRC1 and PRC2 to promote proliferation is a main feature that
      links polycomb (PcG) activity to cancer. PcGs silence the expression of the
      tumour suppressor locus Ink4a/Arf, whose products positively regulate pRb and p53
      functions. Enhanced PcG activity is a frequent feature of human tumours, and PcG
      inhibition has been proposed as a strategy for cancer treatment. However, the
      recurrent inactivation of pRb/p53 responses in human cancers raises a question
      regarding the ability of PcG proteins to affect cellular proliferation
      independently from this checkpoint. Here we demonstrate that PRCs regulate
      cellular proliferation and transformation independently of the Ink4a/Arf-pRb-p53
      pathway. We provide evidence that PRCs localize at replication forks, and that
      loss of their function directly affects the progression and symmetry of DNA
      replication forks. Thus, we have identified a novel activity by which PcGs can
      regulate cell proliferation independently of major cell cycle restriction
      checkpoints. 

PMID- 24728137
TI  - Cu2O-templated strategy for synthesis of definable hollow architectures.
AB  - The template-strategy is one of the most significant techniques for the
      controllable synthesis of hollow architectures with unique structures,
      morphologies and properties. In this review, we selectively summarize the general
      principles of the Cu2O-templated strategy for the synthesis of definable hollow
      architectures and cover the recent progress in this area. We elaborate on the use
      of low-cost Cu2O templates for synthesizing different types of hollow cages
      (including copper sulfide, metal oxide, and metal) categorized by their chemical
      reaction mechanisms, followed by the challenges and perspective on Cu2O-templated
      strategy and its potential future directions. 

PMID- 24728138
TI  - Prevention or early cure of type 1 diabetes by intranasal administration of
      gliadin in NOD mice.
AB  - Induction of long-term tolerance to beta-cell autoantigens has been investigated
      both in animal models and in human type 1 diabetes (T1D) in order to prevent the
      disease. As regards external compounds, the dietary plant protein fraction has
      been associated with high penetrance of the disease, whereas gluten-free diets
      prevent T1D in animal models. Herewith we investigated whether intranasal (i.n.)
      administration of gliadin or gluten may arrest the diabetogenic process. I.n.
      administration of gliadin to 4-week-old NOD mice significantly reduced the
      diabetes incidence. Similarly, the insulitis was lowered. Intranasal gliadin also
      rescued a fraction of prediabetic 13-week-old NOD mice from progressing to
      clinical onset of diabetes compared to OVA-treated controls. Vaccination with
      i.n. gliadin led to an induction of CD4(+)Foxp3(+) T cells and even more
      significant induction of gammadelta T cells in mucosal, but not in non-mucosal
      lymphoid compartments. This prevention strategy was characterized by an increased
      proportion of IL-10 and a decreased proportion of IL-2, IL-4 and IFN-gamma
      positive CD4(+)Foxp3(+) T cells, and IFN-gamma-positive gammadelta T cells,
      preferentially in mucosal lymphoid organs. In conclusion, i.n. vaccination with
      gliadin, an environmental antigen with possible etiological influence in T1D, may
      represent a novel, safer strategy for prevention or even early cure of T1D.

PMID- 24728139
TI  - DIC score in pregnant women--a population based modification of the International
      Society on Thrombosis and Hemostasis score.
AB  - OBJECTIVES: The objectives of this study were: 1) To determine the component
      needed to generate a validated DIC score during pregnancy. 2) To validate such
      scoring system in the identification of patients with clinical diagnosis of DIC.
      MATERIAL AND METHODS: This is a population based retrospective study, including
      all women who gave birth at the 'Soroka University Medical Center' during the
      study period, and have had blood coagulation tests including complete blood cell
      count, prothrombin time (PT)(seconds), partial thromboplastin time (aPTT),
      fibrinogen, and D-dimers. Nomograms for pregnancy were established, and DIC score
      was constructed based on ROC curve analyses. RESULTS: 1) maternal plasma
      fibrinogen concentrations increased during pregnancy; 2) maternal platelet count
      decreased gradually during gestation; 3) the PT and PTT values did not change
      with advancing gestation; 4) PT difference had an area under the curve (AUC) of
      0.96 (p<0.001), and a PT difference >=1.55 had an 87% sensitivity and 90%
      specificity for the diagnosis of DIC; 5) the platelet count had an AUC of 0.87
      (p<0.001), an 86% sensitivity and 71% specificity for the diagnosis of DIC; 6)
      fibrinogen concentrations had an AUC of 0.95 (p<0.001) and a cutoff point <=3.9
      g/L had a sensitivity of 87% and a specificity of 92% for the development of DIC;
      and 7) The pregnancy adjusted DIC score had an AUC of 0.975 (p<0.001) and at a
      cutoff point of >=26 had a sensitivity of 88%, a specificity of 96%, a LR(+) of
      22 and a LR(-) of 0.125 for the diagnosis of DIC. CONCLUSION: We could establish
      a sensitive and specific pregnancy adjusted DIC score. The positive likelihood
      ratio of this score suggests that a patient with a score of >=26 has a high
      probability to have DIC.

PMID- 24728140
TI  - Implicit and explicit timing in oculomotor control.
AB  - The passage of time can be estimated either explicitly, e.g. before leaving home
      in the morning, or implicitly, e.g. when catching a flying ball. In the present
      study, the latency of saccadic eye movements was used to evaluate differences
      between implicit and explicit timing. Humans were required to make a saccade
      between a central and a peripheral position on a computer screen. The delay
      between the extinction of a central target and the appearance of an eccentric
      target was the independent variable that could take one out of four different
      values (400, 900, 1400 or 1900 ms). In target trials, the delay period lasted for
      one of the four durations randomly. At the end of the delay, a saccade was
      initiated by the appearance of an eccentric target. Cue&target trials were
      similar to target trials but the duration of the delay was visually cued. In
      probe trials, the duration of the upcoming delay was cued, but there was no
      eccentric target and subjects had to internally generate a saccade at the
      estimated end of the delay. In target and cue&target trials, the mean and
      variance of latency distributions decreased as delay duration increased. In
      cue&target trials latencies were shorter. In probe trials, the variance increased
      with increasing delay duration and scalar variability was observed. The major
      differences in saccadic latency distributions were observed between visually
      guided (target and cue&target trials) and internally-generated saccades (probe
      trials). In target and cue&target trials the timing of the response was implicit.
      In probe trials, the timing of the response was internally-generated and
      explicitly based on the duration of the visual cue. Scalar timing was observed
      only during probe trials. This study supports the hypothesis that there is no
      ubiquitous timing system in the brain but independent timing processes active
      depending on task demands. 

PMID- 24728141
TI  - Effects of changes in water intake on mood of high and low drinkers.
AB  - OBJECTIVE: To evaluate the effects of a change in water intake on mood and
      sensation in 22 habitual high-volume (HIGH; 2-4 L/d) and 30 low-volume (LOW; <1.2
      L/d) drinkers who were asked to respectively decrease and increase their daily
      water intake. METHOD: During baseline HIGH consumed 2.5 L and LOW 1 L of
      water/day. During 3 controlled intervention days HIGH's water intake was
      restricted to 1 L/day whereas LOW's was increased to 2.5 L water/day. Several
      mood scales (Bond & Lader Visual Analog Scale (VAS), Profile of Mood States,
      Karolinska Sleepiness Scale, Thirst & Emotional VAS) were administered at
      different time points during the study. ANOVA including intervention, time point
      and intervention by time point as fixed effects on mean values (i.e.; baseline
      data vs. mean of 3 intervention days) for each mood scale was performed. RESULTS:
      At baseline HIGH and LOW were comparable in mood state, except for thirst scores
      (estimate = 17.16, p<0.001) and POMS depression-dejection scores (estimate =
      0.55, p<0.05) which were both higher in the HIGH vs. LOW. In HIGH the restricted
      water intake resulted in a significant increase in thirst (p<0.001) and a
      decrease in contentedness (p<0.05), calmness (p<0.01), positive emotions (p<0.05)
      and vigor/activity (p<0.001). In LOW, increased water consumption resulted in a
      significant decrease in fatigue/inertia (p<0.001), confusion/bewilderment (p =
      0.05) and thirst (p<0.001) and a trend to lower sleepiness (p = 0.07) compared to
      baseline. CONCLUSION: Increasing water intake has beneficial effects in LOW,
      especially sleep/wake feelings, whereas decreasing water intake has detrimental
      effects on HIGH's mood. These deleterious effects in HIGH were observed in some
      sleep/wake moods as well as calmness, satisfaction and positive emotions.

PMID- 24728143
TI  - Atomistic simulation of transport phenomena in nanoelectronic devices.
AB  - Computational chemistry deals with the first-principles calculation of electronic
      and crystal structures, phase diagrams, charge distributions, vibrational
      frequencies, or ion diffusivity in complex molecules and solids. Typically, none
      of these numerical experiments allows for the calculation of electrical currents
      under the influence of externally applied voltages. To address this issue, there
      is an imperative need for an advanced simulation approach capable of treating all
      kind of transport phenomena (electron, energy, momentum) at a quantum mechanical
      level. The goal of this tutorial review is to give an overview of the "quantum
      transport" (QT) research activity, introduce specific techniques such as the Non
      equilibrium Green's Function (NEGF) formalism, describe their basic features, and
      underline their strengths and weaknesses. Three examples from the nanoelectronics
      field have been selected to illustrate the insight provided by quantum transport
      simulations. Details are also given about the numerical algorithms to solve the
      NEGF equations and about strategies to parallelize the workload on
      supercomputers. 

PMID- 24728142
TI  - Systemic and mucosal immune reactivity upon Mycobacterium avium ssp.
      paratuberculosis infection in mice.
AB  - Mycobacterium avium ssp. paratuberculosis (MAP) is the cause of Johne's disease,
      an inflammatory bowel disorder of ruminants. Due to the similar pathology, MAP
      was also suggested to cause Crohn's disease (CD). Despite of intensive research,
      this question is still not settled, possibly due to the lack of versatile mouse
      models. The aim of this study was to identify basic immunologic mechanisms in
      response to MAP infection. Immune compromised C57BL/6 Rag2-/- mice were infected
      with MAP intraperitoneally. Such chronically infected mice were then
      reconstituted with CD4+ and CD8+ T cells 28 days after infection. A systemic
      inflammatory response, detected as enlargement of the spleen and granuloma
      formation in the liver, was observed in mice infected and reconstituted with CD4+
      T cells. Whereby inflammation in infected and CD4+CD45RB(hi) T cell reconstituted
      animals was always higher than in the other groups. Reconstitution of infected
      animals with CD8+ T cells did not result in any inflammatory signs.
      Interestingly, various markers of inflammation were strongly up-regulated in the
      colon of infected mice reconstituted with CD4+CD45RB(lo/int) T cells. We propose,
      the usual non-colitogenic CD4+CD45RB(lo/int) T cells were converted into
      inflammatory T cells by the interaction with MAP. However, the power of such
      cells might be not sufficient for a fully established inflammatory response in
      the colon. Nevertheless, our model system appears to mirror aspects of an
      inflammatory bowel disease (IBD) like CD and Johne's diseases. Thus, it will
      provide an experimental platform on which further knowledge on IBD and the
      involvement of MAP in the induction of CD could be acquired.

PMID- 24728144
TI  - Nano-ceramic support materials for low temperature fuel cell catalysts.
AB  - Low temperature fuel cells (LTFCs) have received broad attention due to their low
      operating temperature, virtually zero emissions, high power density and
      efficiency. However, the limited stability of the catalysts is a critical
      limitation to the large scale commercialization of LTFCs. State of the art carbon
      supports undergo corrosion under harsh chemical and electrochemical oxidation
      conditions, which results in performance degradation of catalysts. Therefore, non
      carbon materials which are highly oxidation resistant under strongly oxidizing
      conditions of LTFCs are ideal alternative supports. This minireview highlights
      the advances and scenarios in using nano-ceramics as supports to enhance the
      stability of catalysts, the solutions to improve electrical conductivity of nano
      ceramic materials, and the synergistic effects between metal catalyst and support
      to help improve the catalytic activity and CO/SO2 tolerance of catalysts. 

PMID- 24728145
TI  - Clinical efficacy of add-back therapy in treatment of endometriosis: a meta
      analysis.
AB  - OBJECTIVE: A meta-analysis was conducted to determine the effectiveness of using
      gonadotropin-releasing hormone analogues (GnRH-a), both with and without hormonal
      add-back therapy, for the management of endometriosis. METHODS: Cochrane library,
      Ovid (Embase) and Pubmed databases were searched between the years 1998 and 2013
      for published, prospective, randomised controlled trials (RCT) that assessed the
      effectiveness of "add-back" therapy for EMs treatment. The meta-analysis was
      performed using RevMan V5.0. The main outcome measures were as follows: lumbar
      spine bone mineral density (BMD) immediately after treatment and after 6 months
      of follow-up; femoral neck BMD; serum estradiol levels; changes in the Kupperman
      index score; the pelvic pain score, including dysmenorrhoea and dyspareunia; and
      pelvic tenderness. RESULTS: A total of 13 RCT, including 945 participants, were
      identified. The evidence suggested that "add-back" therapy was more effective for
      symptom relief than GnRH-a alone. BMD was significantly different when comparing
      "add-back" therapy to GnRH-a alone, both immediately after treatment and at 6
      months. The "add-back" therapy increased serum oestrogen and did not reduce the
      efficacy of GnRH-a for treating dysmenorrhoea and dyspareunia. A variety of add
      back regimens had a same effect for the treatment of endometriosis. CONCLUSIONS:
      "Add-back" therapy, based on the GnRH-a dose, does not reduce the efficacy of
      using GNRH-a for the management of endometriosis. "Add-back" therapy reduced the
      occurrence of side effects that can occur with GnRH-a therapy alone, such as
      osteoporosis and menopausal syndrome. There were no statistically significant
      differences when comparing the effectiveness of a variety of "add-back" regimens
      to each other.

PMID- 24728146
TI  - Electrosurgical bipolar vessel sealing for vaginal hysterectomies.
AB  - BACKGROUND: Vascular clamping of the uterine vessels and the ovarian and broad
      ligaments during vaginal hysterectomies is more difficult than in traditional
      abdominal hysterectomies. We aimed to assess the efficacy of electrosurgical
      bipolar vessel sealing systems (EBVS) as an adequate alternative to traditional
      suturing that could facilitate the accomplishment of securing the vascular
      pedicles. METHODS: We searched MEDLINE (1966-2013), Scopus (2004-2013), POPLINE
      (1973-2013), Cochrane Central (1999-2013) and Google Scholar (2004-2013) search
      engines, along with reference lists from all included studies. RESULTS: Eight
      randomized trials were selected, including 772 patients. We found that operative
      duration did not differ significantly among women treated with EBVS and those
      treated with traditional suture ligation (MD -16.86, 95 % CI -34.77, 1.05).
      Intraoperative blood loss on the other hand was significantly lower in the EBVS
      treated group (MD -49.47, 95 % CI -67.60, -31.35). There were no significant
      differences in intraoperative complication rates (OR 0.96, 95 % CI 0.46, 2.01),
      major postoperative complication rates (OR 0.61, 95 % CI 0.29, 1.32) or minor
      complications (OR 1.63, 95 % CI 0.67, 3.92). CONCLUSION: Our meta-analysis showed
      that EBVS seem to produce less intraoperative blood loss during vascular
      clamping, without significantly lowering intraoperative time or complication
      rate. However, the heterogeneity of included studies preclude firm conclusions.
      Future studies examine consistently their safety, and cost-effectiveness, and
      whether the application of such units will enhance the rates of vaginal
      hysterectomies.

PMID- 24728147
TI  - Evidence and causation in mental capacity assessments PC v City of York Council
      [2013] EWCA CIV 478.
AB  - McFarlane LJ's leading judgment in PC v City of York Council consistently
      stresses the 'plain' statutory language of the Mental Capacity Act 2005. In doing
      so, it reveals how intractably difficult performing an assessment in accord with
      the Act can sometimes be. In particular, it raises questions about the sources of
      evidence upon which a finding of incapacity can be based, illustrates that
      causation under the Act may have been widely neglected, and highlights
      contestable assumptions that underlie the Act's 'decision-specific' approach to
      assessment. 

PMID- 24728148
TI  - In vitro and in vivo effects of a nutrient mixture on breast cancer progression.
AB  - Long-term survival of patients with breast cancer remains poor, due to metastasis
      and recurrence. We investigated the effects of a novel nutrient mixture (NM)
      containing ascorbic acid, lysine, proline and green tea extract in vitro and in
      vivo on 4T1 murine breast cancer, a representative model for metastatic breast
      cancer. After one week of isolation, 5-6-week-old female Balb/C mice were
      inoculated with 5x105 4T1 cells into the mammary pad and randomly divided into
      two groups; the control group was fed a regular diet and the NM group a regular
      diet supplemented with 0.5% NM. After four weeks, the mice were sacrificed and
      their tumors, lungs, livers, kidneys, hearts and spleens were excised and
      processed for histology. Dimensions (length and width) of tumors were measured
      using a digital caliper, and the tumor burden was calculated using the following
      formula: 0.5 x length x width. We also tested the effect of NM in vitro on 4T1
      cells, measuring cell proliferation by MTT assay, MMP secretion by zymography,
      invasion through Matrigel, migration by scratch test and morphology by H&E
      staining. NM inhibited tumor weight and burden of 4T1 tumors by 50% (p=0.02) and
      53.4% (p<=0.0001), respectively. Lung metastasis was profoundly inhibited by NM
      supplementation: mean number of colonies was reduced by 87% (p<0.0001) and mean
      weight of lungs by 60% (p=0.0001) compared to control mice. Metastasis to liver,
      spleen, kidney and heart was significantly reduced with NM supplementation. In
      vitro, NM exhibited 50% toxicity over the control at 250 and 500 ug/ml
      concentrations. Zymography demonstrated MMP-2 and MMP-9 secretion which was
      inhibited by NM in a dose-dependent manner, with virtual total inhibition of both
      at 1,000 ug/ml. Migration by scratch test and invasion through Matrigel were
      inhibited in a dose-dependent manner with total block of invasion at 250 and of
      migration at 1,000 ug/ml. These results suggest that NM has therapeutic potential
      in the treatment of breast cancer.

PMID- 24728149
TI  - miR-34a modulates angiotensin II-induced myocardial hypertrophy by direct
      inhibition of ATG9A expression and autophagic activity.
AB  - Cardiac hypertrophy is characterized by thickening myocardium and decreasing in
      heart chamber volume in response to mechanical or pathological stress, but the
      underlying molecular mechanisms remain to be defined. This study investigated
      altered miRNA expression and autophagic activity in pathogenesis of cardiac
      hypertrophy. A rat model of myocardial hypertrophy was used and confirmed by
      heart morphology, induction of cardiomyocyte autophagy, altered expression of
      autophagy-related ATG9A, LC3 II/I and p62 proteins, and decrease in miR-34a
      expression. The in vitro data showed that in hypertrophic cardiomyocytes induced
      by Ang II, miR-34a expression was downregulated, whereas ATG9A expression was up
      regulated. Moreover, miR-34a was able to bind to ATG9A 3'-UTR, but not to the
      mutated 3'-UTR and inhibited ATG9A protein expression and autophagic activity.
      The latter was evaluated by autophagy-related LC3 II/I and p62 levels, TEM, and
      flow cytometry in rat cardiomyocytes. In addition, ATG9A expression induced
      either by treatment of rat cardiomyocytes with Ang II or ATG9A cDNA transfection
      upregulated autophagic activity and cardiomyocyte hypertrophy in both morphology
      and expression of hypertrophy-related genes (i.e., ANP and beta-MHC), whereas
      knockdown of ATG9A expression downregulated autophagic activity and cardiomyocyte
      hypertrophy. However, miR-34a antagonized Ang II-stimulated myocardial
      hypertrophy, whereas inhibition of miR-34a expression aggravated Ang II
      stimulated myocardial hypertrophy (such as cardiomyocyte hypertrophy-related ANP
      and beta-MHC expression and cardiomyocyte morphology). This study indicates that
      miR-34a plays a role in regulation of Ang II-induced cardiomyocyte hypertrophy by
      inhibition of ATG9A expression and autophagic activity. 

PMID- 24728157
TI  - Biochar and Glomus caledonium influence Cd accumulation of upland kangkong
      (Ipomoea aquatica Forsk.) intercropped with Alfred stonecrop (Sedum alfredii
      Hance).
AB  - Both biochar application and mycorrhizal inoculation have been proposed to
      improve plant growth and alter bioaccumulation of toxic metals. A greenhouse pot
      trial was conducted to investigate growth and Cd accumulation of upland kangkong
      (Ipomoea aquatica Forsk.) intercropped with Alfred stonecrop (Sedum alfredii
      Hance) in a Cd-contaminated soil inoculated with Glomus caledonium and/or applied
      with biochar. Compared with the monocultural control, intercropping with
      stonecrop (IS) decreased kangkong Cd acquisition via rhizosphere competition, and
      also decreased kangkong yield. Gc inoculation (+M) accelerated growth and Cd
      acquisition of stonecrop, and hence resulted in further decreases in kangkong Cd
      acquisition. Regardless of IS and +M, biochar addition (+B) increased kangkong
      yield via elevating soil available P, and decreased soil Cd phytoavailability and
      kangkong Cd concentration via increasing soil pH. Compared with the control, the
      treatment of IS + M + B had a substantially higher kangkong yield (+25.5%) with a
      lower Cd concentration (-62.7%). Gc generated additive effects on soil
      alkalinization and Cd stabilization to biochar, causing lower DTPA-extractable
      (phytoavailable) Cd concentrations and post-harvest transfer risks. 

PMID- 24728158
TI  - Vitamin D and diabetes mellitus: an update 2013.
AB  - Vitamin D deficiency and diabetes mellitus are two common conditions and they are
      widely prevalent across all ages, races, geographical regions, and socioeconomic
      conditions. Epidemiologic studies have shown association of vitamin D deficiency
      and increased risk of chronic diseases, such as cancer, cardiovascular disease,
      type 2 diabetes, and autoimmune diseases, such as multiple sclerosis and type 1
      diabetes mellitus. The identification of 1,25(OH)2D receptors and 1-alpha
      hydroxilase expression in pancreatic beta cells, in cells of the immune system,
      and in various others tissues, besides the bone system support the role of
      vitamin D in the pathogenesis of type 2 diabetes. Observational studies have
      revealed an association between 25(OH) D deficiency and the prevalence of type 1
      diabetes in children and adolescents. This review will focus on the concept of
      vitamin D deficiency, its prevalence, and its role in the pathogenesis and risk
      of diabetes mellitus and cardiovascular diseases.

PMID- 24728159
TI  - Challenges and pitfalls in the diagnosis of hyperprolactinemia.
AB  - The definition of the etiology of hyperprolactinemia often represents a great
      challenge and an accurate diagnosis is paramount before treatment. Although
      prolactin levels > 200-250 ng/mL are highly suggestive of prolactinomas, they can
      occasionally be found in other conditions. Moreover, as much as 25% of patients
      with microprolactinomas may present prolactin levels < 100 ng/mL, which are found
      in most patients with pseudoprolactinomas, drug-induced hyperprolactinemia, or
      systemic diseases. On the other hand, some conditions may lead to falsely low PRL
      levels, particularly the so-called hook effect, that is an assay artifact caused
      by an extremely high level of PRL, and can be confirmed by repeating assay after
      a 1:100 serum sample dilution. The hook effect must be considered in all patients
      with large pituitary adenomas and PRL levels within the normal range or only
      modestly elevated (e.g., < 200 ng/mL). An overlooked hook effect may lead to
      incorrect diagnosis and unnecessary surgical intervention in patients with
      prolactinomas. Another important challenge is macroprolactinemia, a common
      finding that needs to be identified, as it usually requires no treatment.
      Although most macroprolactinemic patients are asymptomatic, many of them may
      present galactorrhea or menstrual disorders, as well as neuroradiological
      abnormalities, due to the concomitance of other diseases. Finally, physicians
      should be aware that pituitary incidentalomas are found in at least 10% of adult
      population.

PMID- 24728161
TI  - The value of red blood cell distribution width in subclinical hypothyroidism.
AB  - OBJECTIVE: Therefore, we evaluated the relationship between the subclinical
      hypothyroidism and red cell distribution width (RDW) levels in a healthy
      population. SUBJECTS AND METHODS: The medical records of 23,343 consecutive
      health subjects were reviewed. Subjects were classified into four thyroid
      stimulating hormone (TSH) groups to determine the correlation between TSH and
      other variables in detail (0.3 to < 2.5 mU/L, 2.5 to < 5 mU/L, 5 to < 7.5 mU/L,
      and >= 7.5 mU/L). RESULTS: In the multivariate linear regression analysis, RDW
      was associated with TSH levels, and e-GFR was inversely associated with TSH
      levels, respectively (standardized beta coefficient = 0.102, -0.019; p < 0.001, p
      < 0.001). After adjusting for age and sex, in the four groups, TSH levels were
      significantly correlated with RDW, estimated glomerular filtration rate (e-GFR),
      and free thyroxine (fT4) levels in all groups. Furthermore in the 4 th group, RDW
      levels were more strongly associated with TSH levels than in the other groups (p
      = 0.006). CONCLUSIONS: RDW levels are correlated with euthyroid and subclinical
      thyroid status. Notably, RDW is more correlated with subclinical hypothyroidism
      than the euthyroid status. This study presents the relationship between the RDW
      levels and thyroid function using TSH level in a large healthy population.

PMID- 24728160
TI  - Comparison between the growth response to growth hormone (GH) therapy in children
      with partial GH insensitivity or mild GH deficiency.
AB  - OBJECTIVES: GH therapy is still controversial, except in severe GH deficiency
      (SGHD). The objective of this study was to compare the response to growth hormone
      (GH) therapy in children with partial GH insensitivity (PGHIS) and mild GH
      deficiency (MGHD) with those with SGHD. SUBJECTS AND METHODS: Fifteen PGHIS, 11
      MGHD, and 19 SGHD subjects, followed up for more than one year in the Brazilian
      public care service, were evaluated regarding anthropometric and laboratory data
      at the beginning of treatment, after one year (1st year) on treatment, and at the
      last assessment (up to ten years in SGHD, up to four years in MGHD, and up to
      eight years in PGHIS). RESULTS: Initial height standard deviation score (SDS) in
      SGHD was lower than in MGHD and PGHIS. Although the increase in 1 st year height
      SDS in comparison to initial height SDS was not different among the groups,
      height-SDS after the first year of treatment remained lower in SGHD than in MGHD.
      There was no difference in height-SDS at the last assessment of the children
      among the three groups. GH therapy, in the entire period of observation, caused a
      trend towards lower increase in height SDS in PGHIS than SGHD but similar
      increases were observed in MGHD and SGHD. CONCLUSION: GH therapy increases height
      in PGHIS and produces similar height effects in MGHD and SGHD.

PMID- 24728162
TI  - Response to sorafenib treatment in advanced metastatic thyroid cancer.
AB  - OBJECTIVE: To investigate the efficacy of sorafenib in progressive radioiodine
      resistant metastatic thyroid carcinoma. SUBJECTS AND METHODS: Off-label
      observational study. Sorafenib 400 mg twice daily was evaluated. Therapy duration
      was 12 +/- 3 months (range 6-16 months). RESULTS: Eight patients were included
      (seven papillary, one insular variant). The eight patients meeting study criteria
      received sorafenib 400 mg orally twice a day until disease progression or
      unacceptable toxicity developed. One patient showed a partial response with tumor
      regression of -35%, six months after the beginning of the treatment; five
      patients exhibited stable disease and two patients had progressive disease and
      died. Thyroglobulin decreased within 4 weeks in all patients by 50% +/- 23%.
      Adverse events: one patient had heart failure, and recovered after sorafenib
      withdrawal. However, she died five months later of sudden death. CONCLUSION:
      These data suggest a possible role for sorafenib in the treatment of progressive
      metastatic DTC. Adverse event are usually manageable, but severe ones may appear
      and these patients should be strictly controlled.

PMID- 24728163
TI  - Impact of metformin treatment and swimming exercise on visfatin levels in high
      fat-induced obesity rats.
AB  - OBJECTIVE: Visfatin is a recently discovered adipocytokine that contributes to
      glucose and obesity-related conditions. Until now, its responses to the insulin
      sensitizing agent metformin and to exercise are largely unknown. We aim to
      investigate the impact of metformin treatment and/or swimming exercise on serum
      visfatin and visfatin levels in subcutaneous adipose tissue (SAT), peri-renal
      adipose tissue (PAT) and skeletal muscle (SM) of high-fat-induced obesity rats.
      MATERIALS AND METHODS: Sprague-Dawley rats were fed a normal diet or a high-fat
      diet for 16 weeks to develop obesity model. The high-fat-induced obesity model
      rats were then randomized to metformin (MET), swimming exercise (SWI), or
      adjunctive therapy of metformin and swimming exercise (MAS), besides high-fat
      obesity control group and a normal control group, all with 10 rats per group.
      Zoometric and glycemic parameters, lipid profile, and serum visfatin levels were
      assessed at baseline and after 6 weeks of therapy. Visfatin levels in SAT, PAT
      and SM were determined by Western Blot. RESULTS: Metformin and swimming exercise
      improved lipid profile, and increased insulin sensitivity and body weight
      reduction were observed. Both metformin and swimming exercise down-regulated
      visfatin levels in SAT and PAT, while the adjunctive therapy conferred greater
      benefits, but no changes of visfatin levels were observed in SM. CONCLUSION: Our
      results indicate that visfatin down-regulation in SAT and PAT may be one of the
      mechanisms by which metformin and swimming exercise inhibit obesity.

PMID- 24728164
TI  - Thyroid autoimmunity in patients with hyperprolactinemia: an observational study.
AB  - OBJECTIVE: To establish whether there is a relationship between
      hyperprolactinemia and primary thyroid disorders, focusing on patients with
      autoimmune features. MATERIALS AND METHODS: The medical records of 100 patients
      with hyperprolactinemia (HPRL) were retrospectively examined. Records of thyroid
      ultrasonography (USG), basal serum levels of thyroid stimulating hormone,
      circulating free thyroxine, free triiodothyronine, antithyroglobulin (anti-Tg),
      and antithyroperoxidase (anti-TPO) antibodies were analyzed. In 100 control
      subjects, matched by age and gender with HPRL patients, thyroid USG, thyroid
      function tests (TFTs), and autoantibody panel were obtained. RESULTS: The median
      PRL in patients was 93 ng/mL (range: 37-470). Twenty-five patients (25%) and 22
      controls (22%) had positive anti-Tg and/or anti-TPO titers (P = 0.739). The
      median serum PRL was 98 (37-470) ng/mL in patients with positive thyroid
      autoantibodies, and 92 (40-470) ng/mL in patients who were negative (P = 0.975).
      Among the individuals with autoantibody positivity TFTs abnormalities were more
      frequent in HPRL patients (60%, out of 25 patients, 14 with subclinical
      hypothyroidism and one with hyperthyroidism) than in controls (9.1%, out of 22
      patients, 2 with subclinical hyperthyroidism) (P < 0.001). Twenty-seven patients
      with HPRL and 31 controls had goiter (27 vs. 31%, P = 0.437). Forty-six patients
      (46%) and 50 (50%) controls had one or more of the features of thyroid disorder,
      which were goiter, positive thyroid autoantibody, and thyroid function
      abnormality (P = 0.888). CONCLUSION: HPRL may be associated with more severe
      thyroid dysfunction in patients with thyroid autoimmunity.

PMID- 24728165
TI  - NR3C1 polymorphisms in Brazilians of Caucasian, African, and Asian ancestry:
      glucocorticoid sensitivity and genotype association.
AB  - OBJECTIVE: The Brazilian population has heterogeneous ethnicity. No previous
      study evaluated NR3C1 polymorphisms in a Brazilian healthy population. MATERIALS
      AND METHODS: We assessed NR3C1 polymorphisms in Brazilians of Caucasian, African
      and Asian ancestry (n = 380). In a subgroup (n = 40), we compared the genotypes
      to glucocorticoid (GC) sensitivity, which was previously evaluated by plasma (PF)
      and salivary (SF) cortisol after dexamethasone (DEX) suppression tests, GC
      receptor binding affinity (K d ), and DEX-50% inhibition (IC 50 ) of concanavalin
      A-stimulated mononuclear cell proliferation. p.N363S (rs6195), p.ER22/23EK
      (rs6189-6190), and BclI (rs41423247) allelic discrimination was performed by Real
      Time PCR (Polymerase Chain Reaction). Exons 3 to 9 and exon/intron boundaries
      were amplified by PCR and sequenced. RESULTS: Genotypic frequencies (%) were:
      rs6195 (n = 380; AA:96.6/AG:3.14/GG:0.26), rs6189-6190 (n = 264; GG:99.6/GA:0.4),
      rs41423247 (n = 264; CC:57.9/CG:34.1/GG:8.0), rs6188 (n = 155;
      GG:69.6/GT:25.7/TT:4.7), rs258751 (n = 150; CC:88.0/CT:10.7/TT:1.3), rs6196 (n =
      176; TT:77.2/TC:20.4/CC:2.4), rs67300719 (n = 137; CC:99.3/CT:0.7), and
      rs72542757 (n = 137; CC:99.3/CG:0.7). The rs67300719 and rs72542757 were found
      only in Asian descendants, in whom p.N363S and p.ER22/23EK were absent. The
      p.ER22/23EK was observed exclusively in Caucasian descendants. Hardy-Weinberg
      equilibrium was observed, except in the Asian for rs6188 and rs258751, and in the
      African for p.N363S. The K d , IC 50 , baseline and after DEX PF or SF did not
      differ between genotype groups. However, the mean DEX dose that suppressed PF or
      SF differed among the BclI genotypes (P = 0.03). DEX dose was higher in GG- (0.7
      +/- 0.2 mg) compared to GC- (0.47 +/- 0.2 mg) and CC-carriers (0.47 +/- 0.1 mg).
      CONCLUSION: The genotypic frequencies of NR3C1 polymorphisms in Brazilians are
      similar to worldwide populations. Additionally, the BclI polymorphism was
      associated with altered pituitary-adrenal axis GC sensitivity.

PMID- 24728166
TI  - Evaluation of effectiveness and outcome of PKU screening and management in the
      State of Sergipe, Brazil.
AB  - OBJECTIVES: Phenylketonuria (PKU) was the first inherited metabolic disease known
      to cause mental retardation for which a newborn screening program (NBS) was
      developed. The objective of this study was to evaluate the effectiveness of PKU
      NBS and the management of cases in the northeastern Brazilian state of Sergipe
      (SE). MATERIALS AND METHODS: We reviewed the phenylalanine concentrations in
      filter-paper collected from the heel (PKUneo) of 43,449 newborns; blood
      concentrations obtained by venipuncture in the subjects with abnormal PKUneo; the
      children's age at several phases of the program, the incidence of the disease
      from January 2007 to June 2008; and metabolic control of the patients. RESULTS:
      The coverage of NBS/SE was 78.93%. The children's age was 10 +/- 7 days at PKUneo
      collection. Twelve children were recalled based on the PKUneo cutoff value at 28
      +/- 13 days. From these, the concentrations of phenylalanine collected by
      venipuncture were normal in five children. The incidence of hyperphenylalaninemia
      was 1/43,449, and of PKU was 1/8,690 (5 cases). One suspected subject died.
      Another death occurred in the cohort, in a confirmed PKU case. PKU treatment
      began within 51 +/- 12 days of life. In the four patients under dietary
      phenylalanine restriction, metabolic control was often difficult. CONCLUSIONS:
      PKU NBS/SE has satisfactory coverage and adequate cutoff for recalling patients
      and diagnosis, but the onset of treatment is delayed, and follow-up metabolic
      control is frequently inadequate.

PMID- 24728167
TI  - Ovarian Leydig cell tumor in a post-menopausal patient with severe
      hyperandrogenism.
AB  - Leydig cell tumors are rare ovarian steroid cell neoplasms. More than 75% of
      patients show signs of virilization due to overproduction of testosterone. We
      report a case of an 81-year-old woman with progressive signs of virilization, and
      presenting vaginal bleeding. Clinical analyses revealed high levels of serum
      testosterone, delta 4-androstenedione and estradiol, and also inappropriate low
      levels of gonadotrophins for a post-menopausal woman. Transvaginal ultrasound
      showed no evidence of ovarian tumor, but pelvic and abdominal computerized axial
      tomography imaging revealed a left ovarian solid nodule, and no evidence of
      alteration in the adrenal glands. Total hysterectomy and bilateral
      salpingoophorectomy were performed. Histopathology and immunohistochemistry
      confirmed the diagnosis of Leydig cell tumor. After surgery, androgen levels
      returned to normal, and there was regression of the signs of virilization.

PMID- 24728168
TI  - [Endogenous hyperinsulinism: two diagnostic challenges].
AB  - Hypoglycemia in apparently healthy adults is a rare finding in clinical practice
      requiring a thorough investigation of the cause. During the investigation,
      identification of hypoglycemia associated with inappropriately high levels of
      insulin and C-peptide should prompt the exclusion of rare causes of hypoglycemia,
      including pancreatic islet-cells disease and autoimmune hypoglycemia. In this
      paper, we describe two cases of hypoglycemia associated with endogenous
      hyperinsulinism, whose causes are uncommon in clinical practice, and review
      important aspects of the diagnosis and treatment of hyperinsulinemic
      hypoglycemia.

PMID- 24728169
TI  - Spontaneous remission of acromegaly: apoplexy mimicking meningitis or meningitis
      as a cause of apoplexy?
AB  - Pituitary apoplexy is a rare but potentially life-threatening clinical syndrome
      characterized by ischemic infarction or hemorrhage into a pituitary tumor. The
      diagnosis of pituitary tumor apoplexy is frequently complicated because of the
      nonspecific nature of its signs and symptoms, which can mimic different
      neurological processes, including meningitis. Several factors have been
      associated with apoplexy, such as dopamine agonists, radiotherapy, or head
      trauma, but meningitis is a rarely reported cause. We describe the case of a 51
      year-old woman with acromegaly due to a pituitary macroadenoma. Before surgical
      treatment, she arrived at Emergency with fever, nausea, vomiting and meningismus.
      Symptoms and laboratory tests suggested bacterial meningitis, and antibiotic
      therapy was initiated, with quick improvement. A computerized tomography (CT)
      scan at admission did not reveal any change in pituitary adenoma, but a few weeks
      later, magnetic resonance imaging (MRI) showed data of pituitary apoplexy with
      complete disappearance of the adenoma. Currently, her acromegaly is cured, but
      she developed hypopituitarism and diabetes insipidus following apoplexy. We
      question whether she really experienced meningitis leading to apoplexy or whether
      apoplexy was misinterpreted as meningitis. In conclusion, the relationship
      between meningitis and pituitary apoplexy may be bidirectional. Apoplexy can
      mimic viral or bacterial meningitis, but meningitis might cause apoplexy, as
      well. This fact highlights the importance of differential diagnosis when
      evaluating patients with pituitary adenomas and acute neurological symptoms.

PMID- 24728170
TI  - [Lipolysis inhibition as therapeutic target in the metabolic syndrome].

PMID- 24728171
TI  - Preproghrelin polymorphism Q90L (rs4684677) in gestational diabetes.

PMID- 24728172
TI  - Thyroid function and autoimmunity in HIV-infected women.

PMID- 24728173
TI  - Evaluation of thyroid function and autoimmunity in HIV-infected women.

PMID- 24728174
TI  - Contact of cis-Golgi with ER exit sites executes cargo capture and delivery from
      the ER.
AB  - Protein transport from the endoplasmic reticulum (ER) to the Golgi apparatus is
      mediated by coat complex II (COPII) vesicles. It has been believed that COPII
      vesicles containing cargo are released from the ER exit sites (ERES) into the
      cytosol and then reach and fuse with the first post-ER compartment, cis-Golgi or
      ER-to-Golgi intermediate compartment (ERGIC). However, it still remains elusive
      how cargo loading to vesicles, vesicle budding, tethering and fusion are
      coordinated in vivo. Here we show, using extremely high speed and high resolution
      confocal microscopy, that the cis-Golgi in the budding yeast Saccharomyces
      cerevisiae approaches and contacts the ERES. The COPII coat cage then collapses
      and the cis-Golgi captures cargo. The cis-Golgi, thus loaded with cargo, then
      leaves the ERES. We propose that this 'hug-and-kiss' behaviour of cis-Golgi
      ensures efficient and targeted cargo transport from the ERES to cis-Golgi. 

PMID- 24728175
TI  - A facile method for the synthesis of the Li(0.3)La(0.57)TiO3 solid state
      electrolyte.
AB  - We report a facile method for the synthesis of Li(0.3)La(0.57)TiO3 by forming a
      coagulated precursor solution which contains Li(+), La(3+), and TiO2
      nanoparticles mixed highly homogeneously. The grain and overall conductivities of
      the synthesized Li(0.3)La(0.57)TiO3 are comparable to the values in literature
      for the material prepared by other methods.

PMID- 24728176
TI  - ATM-mediated Mad1 Serine 214 phosphorylation regulates Mad1 dimerization and the
      spindle assembly checkpoint.
AB  - The spindle assembly checkpoint (SAC), which blocks anaphase onset until all
      chromosomes have bi-oriented, is one of the key self-monitoring systems of the
      eukaryotic cell cycle for genome stability. The mitotic arrest-deficient protein
      1 (Mad1), a critical component of the SAC, is hyperphosphorylated in mitosis.
      However, the kinases responsible for Mad1 phosphorylation and its functional
      significance are not fully understood. Here we report that Mad1 is phosphorylated
      on Serine 214 by the Ataxia-Telangiectasia Mutated (ATM) kinase, a critical DNA
      damage response protein also activated in mitosis and required for the SAC. We
      demonstrate that Mad1 Serine 214 phosphorylation promotes the formation of
      homodimerization of Mad1 and its heterodimerization with Mad2. Further we show
      that Mad1 Serine 214 phosphorylation contribute to activation of the SAC and the
      maintenance of chromosomal stability. Together, these findings reveal an
      important role of ATM-mediated Mad1 Serine 214 phosphorylation in mitosis. 

PMID- 24728177
TI  - Voltage-dependent structural changes of the membrane-bound anion channel hVDAC1
      probed by SEIRA and electrochemical impedance spectroscopy.
AB  - The voltage-dependent anion channel (VDAC) is a transmembrane protein that
      regulates the transfer of metabolites between the cytosol and the mitochondrium.
      Opening and partial closing of the channel is known to be driven by the
      transmembrane potential via a mechanism that is not fully understood. In this
      work, we employed a spectroelectrochemical approach to probe the voltage-induced
      molecular structure changes of human VDAC1 (hVDAC1) embedded in a tethered
      bilayer lipid membrane on a nanostructured Au electrode. The model membrane
      consisted of a mixed self-assembled monolayer of 6-mercaptohexanol and
      (cholesterylpolyethylenoxy)thiol, followed by the deposition of 1-palmitoyl-2
      oleoyl-sn-glycero-3-phosphocholine vesicles including hVDAC1. The stepwise
      assembly of the model membrane and the incorporation of hVDAC1 were monitored by
      surface enhanced infrared absorption and electrochemical impedance spectroscopy.
      Difference spectra allowed for identifying the spectral changes which may be
      associated with the transition from the open to the "closed" states by shifting
      the potential above or below the transmembrane potential determined to be ca. 0.0
      V vs. the open circuit potential. These spectral changes were interpreted on the
      basis of the orientation- and distance-dependent IR enhancement and indicate
      alterations of the inclination angle of the beta-strands as crucial molecular
      events, reflecting an expansion or contraction of the beta-barrel pore. These
      protein structural changes that do not confirm nor exclude the reorientation of
      the alpha-helix are either directly induced by the electric field or a
      consequence of a potential-dependent repulsion or attraction of the bilayer. 

PMID- 24728178
TI  - Postural stability in young adults with Down syndrome in challenging conditions.
AB  - To evaluate postural control and performance in subjects with Down syndrome
      (SwDS), we measured postural sway (COP) in quiet stance in four 20-second tests:
      with eyes open or closed and on hard or foam surface. Ten SwDS and eleven healthy
      subjects participated, aged 29.8 (4.8) and 28.4 (3.9), respectively. The time
      series recorded with the sampling rate of 100 Hz were used to evaluate postural
      performance (COP amplitude and mean velocity) and strategies (COP frequency,
      fractal dimension and entropy). There were no intergroup differences in the
      amplitude except the stance on foam pad with eyes open when SwDS had larger sway.
      The COP velocity and frequency were larger in SwDS than controls in all trials on
      foam pad. During stances on the foam pad SwDS increased fractal dimension showing
      higher complexity of their equilibrium system, while controls decreased sample
      entropy exhibiting more conscious control of posture in comparison to the stances
      on hard support surface. This indicated that each group used entirely different
      adjustments of postural strategies to the somatosensory challenge. It is proposed
      that the inferior postural control of SwDS results mainly from insufficient
      experience in dealing with unpredictable postural stimuli and deficit in motor
      learning. 

PMID- 24728179
TI  - BraX-Ray: an X-ray of the Brazilian computer science graduate programs.
AB  - Research productivity assessment is increasingly relevant for allocation of
      research funds. On one hand, this assessment is challenging because it involves
      both qualitative and quantitative analysis of several characteristics, most of
      them subjective in nature. On the other hand, current tools and academic social
      networks make bibliometric data web-available to everyone for free. Those tools,
      especially when combined with other data, are able to create a rich environment
      from which information on research productivity can be extracted. In this
      context, our work aims at characterizing the Brazilian Computer Science graduate
      programs and the relationship among themselves. We (i) present views of the
      programs from different perspectives, (ii) rank the programs according to each
      perspective and a combination of them, (iii) show correlation between assessment
      metrics, (iv) discuss how programs relate to another, and (v) infer aspects that
      boost programs' research productivity. The results indicate that programs with a
      higher insertion in the coauthorship network topology also possess a higher
      research productivity between 2004 and 2009. 

PMID- 24728181
TI  - The role of T helper 17 cell subsets in Sjogren's syndrome: similarities and
      differences between mouse model and humans.

PMID- 24728180
TI  - A PCNA-derived cell permeable peptide selectively inhibits neuroblastoma cell
      growth.
AB  - Proliferating cell nuclear antigen (PCNA), through its interaction with various
      proteins involved in DNA synthesis, cell cycle regulation, and DNA repair, plays
      a central role in maintaining genome stability. We previously reported a novel
      cancer associated PCNA isoform (dubbed caPCNA), which was significantly expressed
      in a broad range of cancer cells and tumor tissues, but not in non-malignant
      cells. We found that the caPCNA-specific antigenic site lies between L126 and
      Y133, a region within the interconnector domain of PCNA that is known to be a
      major binding site for many of PCNA's interacting proteins. We hypothesized that
      therapeutic agents targeting protein-protein interactions mediated through this
      region may confer differential toxicity to normal and malignant cells. To test
      this hypothesis, we designed a cell permeable peptide containing the PCNA L126
      Y133 sequence. Here, we report that this peptide selectively kills human
      neuroblastoma cells, especially those with MYCN gene amplification, with much
      less toxicity to non-malignant human cells. Mechanistically, the peptide is able
      to block PCNA interactions in cancer cells. It interferes with DNA synthesis and
      homologous recombination-mediated double-stranded DNA break repair, resulting in
      S-phase arrest, accumulation of DNA damage, and enhanced sensitivity to
      cisplatin. These results demonstrate conceptually the utility of this peptide for
      treating neuroblastomas, particularly, the unfavorable MYCN-amplified tumors. 

PMID- 24728182
TI  - Investigation of combined CYP3A4 inductive/inhibitory properties by studying
      statin interactions: a model study with the renin inhibitor ACT-178882.
AB  - PURPOSE: ACT-178882, a direct renin inhibitor, was used as a model compound in an
      elaborate drug-drug interaction study with atorvastatin and simvastatin to
      explore complex CYP3A4 inductive and inhibitory properties. METHODS: Thirty-two
      healthy male subjects received single doses of 20 mg atorvastatin and 20 mg
      simvastatin on days 1, 9, 31, and 41. On days 6 to 33, 500 mg ACT-178882 was
      administered once daily. Plasma concentrations of ACT-178882, simvastatin, and
      atorvastatin were measured by LC-MS/MS. Routine safety assessments were performed
      throughout the study. RESULTS: Exposure (as based on area under the curve) to
      simvastatin and 6beta-hydroxyacid simvastatin increased (90 % confidence
      interval) 4.63-fold (3.90, 5.50) and 3.71-fold (3.19, 4.32), respectively, when
      comparing day 9 and day 1. On day 9, exposure to atorvastatin was similar but
      Cmax decreased, while both variables decreased for ortho-hydroxy atorvastatin
      when compared to day 1. On day 31, after prolonged administration of ACT-178882,
      exposure to atorvastatin, ortho-hydroxy atorvastatin, simvastatin, and 6beta
      hydroxyacid simvastatin decreased by 14, 19, 21, and 27 %, respectively, when
      compared to day 9. However, on this day, exposure to simvastatin and its
      metabolite was still markedly higher when compared to day 1. Effects of ACT
      178882 had largely dissipated on day 41. CONCLUSIONS: This design enabled the
      study of complex time-dependent effects on CYP3A4 activity with clinically
      relevant substrates.

PMID- 24728183
TI  - RUVBL1 directly binds actin filaments and induces formation of cell protrusions
      to promote pancreatic cancer cell invasion.
AB  - We report a novel function of RUVBL1 molecule in pancreatic cancer cells.
      Previous reports describe that RUVBL1 belongs to the family of AAA+ ATPases that
      associate with chromatin-remodelling complexes and have important roles in
      transcriptional regulation, the DNA damage response, telomerase activity and
      cellular transformation. We show that knockdown of RUVBL1 inhibited the motility
      and invasiveness of pancreatic cancer cells. RUVBL1 localized in the cytoplasm
      bound filamentous actin (F-actin) in cell protrusions, and increased
      concentration of monomeric globular-actin (G-actin) in cell protrusions of
      migrating pancreatic cancer cells. Cytoplasmic RUVBL1 functioned in additional
      formation of actin filaments in cell protrusions. Consequently, cytoplasmic
      RUVBL1 contributed to the formation of membrane protrusions by promoting
      peripheral actin polymerization. Our results imply that these RUVBL1-actin
      interactions could enhance the invasive properties of pancreatic cancer cells. 

PMID- 24728184
TI  - Nanoplasmonics.

PMID- 24728187
TI  - The novel Parkinson's disease linked mutation G51D attenuates in vitro
      aggregation and membrane binding of alpha-synuclein, and enhances its secretion
      and nuclear localization in cells.
AB  - A novel mutation in the alpha-Synuclein (alpha-Syn) gene "G51D" was recently
      identified in two familial cases exhibiting features of Parkinson's disease (PD)
      and multiple system atrophy (MSA). In this study, we explored the impact of this
      novel mutation on the aggregation, cellular and biophysical properties of alpha
      Syn, in an attempt to unravel how this mutant contributes to PD/MSA. Our results
      show that the G51D mutation significantly attenuates alpha-Syn aggregation in
      vitro. Moreover, it disrupts local helix formation in the presence of SDS,
      decreases binding to lipid vesicles C-terminal to the site of mutation and
      severely inhibits helical folding in the presence of acidic vesicles. When
      expressed in yeast, alpha-Syn(G51D) behaves similarly to alpha-Syn(A30P), as both
      exhibit impaired membrane association, form few inclusions and are non-toxic. In
      contrast, enhanced secreted and nuclear levels of the G51D mutant were observed
      in mammalian cells, as well as in primary neurons, where alpha-Syn(G51D) was
      enriched in the nuclear compartment, was hyper-phosphorylated at S129 and
      exacerbated alpha-Syn-induced mitochondrial fragmentation. Finally, post-mortem
      human brain tissues of alpha-Syn(G51D) cases were examined, and revealed only
      partial colocalization with nuclear membrane markers, probably due to post-mortem
      tissue delay and fixation. These findings suggest that the PD-linked mutations
      may cause neurodegeneration via different mechanisms, some of which may be
      independent of alpha-Syn aggregation. 

PMID- 24728188
TI  - No large-effect low-frequency coding variation found for myocardial infarction.
AB  - Genome-wide association studies have identified variants, primarily common, that
      are associated with coronary artery disease or myocardial infarction (MI), but
      have not tested the majority of the low frequency and rare variation in the
      genome. We explored the hypothesis that previously untested low frequency (1-5%
      minor allele frequency) and rare (<1% minor allele frequency) coding variants are
      associated with MI. We genotyped 2906 MI cases and 6738 non-MI controls from
      Norway using the Illumina HumanExome Beadchip, allowing for direct genotyping of
      85 972 polymorphic coding variants as well as 48 known GWAS SNPs. We followed-up
      34 coding variants in an additional 2350 MI cases and 2318 controls from Norway.
      We evaluated exome array coverage in a subset of these samples using whole exome
      sequencing (N = 151). The exome array provided successful genotyping for an
      estimated 72.5% of Norwegian loss-of-function or missense variants with frequency
      >1% and 66.2% of variants <1% frequency observed more than once. Despite 80%
      power in the two-stage study (N = 14 312) to detect association with low
      frequency variants with high effect sizes [odds ratio (OR) >1.86 and >1.36 for 1
      and 5% frequency, respectively], we did not identify any novel genes or single
      variants that reached significance. This suggests that low-frequency coding
      variants with large effect sizes (OR >2) may not exist for MI. Larger sample
      sizes may identify coding variants with more moderate effects. 

PMID- 24728189
TI  - The contribution of deleterious germline mutations in BRCA1, BRCA2 and the
      mismatch repair genes to ovarian cancer in the population.
AB  - The aim of this study was to estimate the contribution of deleterious mutations
      in BRCA1, BRCA2, MLH1, MSH2, MSH6 and PMS2 to invasive epithelial ovarian cancer
      (EOC) in the population. The coding sequence and splice site boundaries of all
      six genes were amplified in germline DNA from 2240 invasive EOC cases and 1535
      controls. Barcoded fragment libraries were sequenced using the Illumina GAII or
      HiSeq and sequence data for each subject de-multiplexed prior to interpretation.
      GATK and Annovar were used for variant detection and annotation. After quality
      control 2222 cases (99.2%) and 1528 controls (99.5%) were included in the final
      analysis. We identified 193 EOC cases (8.7%) carrying a deleterious mutation in
      at least one gene compared with 10 controls (0.65%). Mutations were most frequent
      in BRCA1 and BRCA2, with 84 EOC cases (3.8%) carrying a BRCA1 mutation and 94 EOC
      cases (4.2%) carrying a BRCA2 mutation. The combined BRCA1 and BRCA2 mutation
      prevalence was 11% in high-grade serous disease. Seventeen EOC cases carried a
      mutation in a mismatch repair gene, including 10 MSH6 mutation carriers (0.45%)
      and 4 MSH2 mutation carriers (0.18%). At least 1 in 10 women with high-grade
      serous EOC has a BRCA1 or BRCA2 mutation. The development of next generation
      sequencing technologies enables rapid mutation screening for multiple
      susceptibility genes at once, suggesting that routine clinical testing of all
      incidence cases should be considered. 

PMID- 24728190
TI  - Progressive axonal transport and synaptic protein changes correlate with
      behavioral and neuropathological abnormalities in the heterozygous Q175 KI mouse
      model of Huntington's disease.
AB  - A long-term goal of modeling Huntington's disease (HD) is to recapitulate the
      cardinal features of the disease in mice that express both mutant and wild-type
      (WT) huntingtin (Htt), as HD commonly manifests as a heterozygous condition in
      humans, and loss of WT Htt is associated with loss-of-function. In a new
      heterozygous Q175 knock-in (KI) mouse model, we performed an extensive evaluation
      of motor and cognitive functional deficits, neuropathological and biochemical
      changes and levels of proteins involved in synaptic function, the cytoskeleton
      and axonal transport, at 1-16 months of age. Motor deficits were apparent at 6
      months of age in Q175 KI mice and at that time, postmortem striatal gamma
      aminobutyric acid (GABA) levels were elevated and mutant Htt inclusions were
      present throughout the brain. From 6 months of age, levels of proteins associated
      with synaptic function, including SNAP-25, Rab3A and PSD-95, and with axonal
      transport and microtubules, including KIF3A, dynein and dynactin, were altered in
      the striatum, motor cortex, prefrontal cortex and hippocampus of Q175 KI mice,
      compared with WT levels. At 12-16 months of age, Q175 KI mice displayed motor and
      cognitive deficits, which were paralleled at postmortem by striatal atrophy,
      cortical thinning, degeneration of medium spiny neurons, dense mutant Htt
      inclusion formation, decreased striatal dopamine levels and loss of striatal
      brain-derived neurotrophic factor (BDNF). Data from this study indicate that the
      heterozygous Q175 KI mouse represents a realistic model for HD and also provides
      new insights into the specific and progressive synaptic, cytoskeletal and axonal
      transport protein abnormalities that may accompany the disease. 

PMID- 24728191
TI  - Phosphate starvation in fungi induces the replacement of phosphatidylcholine with
      the phosphorus-free betaine lipid diacylglyceryl-N,N,N-trimethylhomoserine.
AB  - Diacylglyceryl-N,N,N-trimethylhomoserine (DGTS) is a phosphorus-free betaine
      lipid analog of phosphatidylcholine (PtdCho) synthesized by many soil bacteria,
      algae, and nonvascular plants. Synthesis of DGTS and other phosphorus-free lipids
      in bacteria occurs in response to phosphorus (P) deprivation and results in the
      replacement of phospholipids by nonphosphorous lipids. The genes encoding DGTS
      biosynthetic enzymes have previously been identified and characterized in
      bacteria and the alga Chlamydomonas reinhardtii. We now report that many fungal
      genomes, including those of plant and animal pathogens, encode the enzymatic
      machinery for DGTS biosynthesis, and that fungi synthesize DGTS during P
      limitation. This finding demonstrates that replacement of phospholipids by
      nonphosphorous lipids is a strategy used in divergent eukaryotic lineages for the
      conservation of P under P-limiting conditions. Mutants of Neurospora crassa were
      used to show that DGTS synthase encoded by the BTA1 gene is solely responsible
      for DGTS biosynthesis and is under the control of the fungal phosphorus
      deprivation regulon, mediated by the NUC-1/Pho4p transcription factor.
      Furthermore, we describe the rational reengineering of lipid metabolism in the
      yeast Saccharomyces cerevisiae, such that PtdCho is completely replaced by DGTS,
      and demonstrate that essential processes of membrane biogenesis and organelle
      assembly are functional and support growth in the engineered strain. 

PMID- 24728192
TI  - The mtfA transcription factor gene controls morphogenesis, gliotoxin production,
      and virulence in the opportunistic human pathogen Aspergillus fumigatus.
AB  - Aspergillus fumigatus is the leading causative agent of invasive aspergillosis
      (IA). The number of cases is on the rise, with mortality rates as high as 90%
      among immunocompromised patients. Molecular genetic studies in A. fumigatus could
      provide novel targets to potentially set the basis for antifungal therapies. In
      the current study, we investigated the role of the transcription factor gene mtfA
      in A. fumigatus. Our results revealed that mtfA plays a role in the growth and
      development of the fungus. Deletion or overexpression of mtfA leads to a slight
      reduction in colony growth, as well as a reduction in conidiation levels, in the
      overexpression strain compared to the wild-type strain. Furthermore, production
      of the secondary metabolite gliotoxin increased when mtfA was overexpressed,
      coinciding with an increase in the transcription levels of the gliotoxin genes
      gliZ and gliP with respect to the wild type. In addition, our study showed that
      mtfA is also necessary for normal protease activity in A. fumigatus; deletion of
      mtfA resulted in a reduction of protease activity compared to wild-type levels.
      Importantly, the absence of mtfA caused a decrease in virulence in the Galleria
      mellonella infection model, indicating that mtfA is necessary for A. fumigatus
      wild-type pathogenesis. 

PMID- 24728193
TI  - Histidine degradation via an aminotransferase increases the nutritional
      flexibility of Candida glabrata.
AB  - The ability to acquire nutrients during infections is an important attribute in
      microbial pathogenesis. Amino acids are a valuable source of nitrogen if they can
      be degraded by the infecting organism. In this work, we analyzed histidine
      utilization in the fungal pathogen of humans Candida glabrata. Hemiascomycete
      fungi, like C. glabrata or Saccharomyces cerevisiae, possess no gene coding for a
      histidine ammonia-lyase, which catalyzes the first step of a major histidine
      degradation pathway in most other organisms. We show that C. glabrata instead
      initializes histidine degradation via the aromatic amino acid aminotransferase
      Aro8. Although ARO8 is also present in S. cerevisiae and is induced by
      extracellular histidine, the yeast cannot use histidine as its sole nitrogen
      source, possibly due to growth inhibition by a downstream degradation product.
      Furthermore, C. glabrata relies only on Aro8 for phenylalanine and tryptophan
      utilization, since ARO8, but not its homologue ARO9, was transcriptionally
      activated in the presence of these amino acids. Accordingly, an ARO9 deletion had
      no effect on growth with aromatic amino acids. In contrast, in S. cerevisiae,
      ARO9 is strongly induced by tryptophan and is known to support growth on aromatic
      amino acids. Differences in the genomic structure of the ARO9 gene between C.
      glabrata and S. cerevisiae indicate a possible disruption in the regulatory
      upstream region. Thus, we show that, in contrast to S. cerevisiae, C. glabrata
      has adapted to use histidine as a sole source of nitrogen and that the aromatic
      amino acid aminotransferase Aro8, but not Aro9, is the enzyme required for this
      process. 

PMID- 24728194
TI  - Identification of obscure yet conserved actin-associated proteins in Giardia
      lamblia.
AB  - Consistent with its proposed status as an early branching eukaryote, Giardia has
      the most divergent actin of any eukaryote and lacks core actin regulators.
      Although conserved actin-binding proteins are missing from Giardia, its actin is
      utilized similarly to that of other eukaryotes and functions in core cellular
      processes such as cellular organization, endocytosis, and cytokinesis. We set out
      to identify actin-binding proteins in Giardia using affinity purification coupled
      with mass spectroscopy (multidimensional protein identification technology
      [MudPIT]) and have identified >80 putative actin-binding proteins. Several of
      these have homology to conserved proteins known to complex with actin for
      functions in the nucleus and flagella. We validated localization and interaction
      for seven of these proteins, including 14-3-3, a known cytoskeletal regulator
      with a controversial relationship to actin. Our results indicate that although
      Giardia lacks canonical actin-binding proteins, there is a conserved set of actin
      interacting proteins that are evolutionarily indispensable and perhaps represent
      some of the earliest functions of the actin cytoskeleton. 

PMID- 24728195
TI  - A new strategy of RNA interference that targets heterologous sequences reveals
      CITFA1 as an essential component of class I transcription factor A in Trypanosoma
      brucei.
AB  - Conditional gene silencing by RNA interference in Trypanosoma brucei can be
      inconclusive if knockdowns are inefficient or have off-target effects. To enable
      efficient, specific silencing of single-copy genes in mammalian-infective,
      bloodstream form trypanosomes, we developed a system that targets the
      heterologous and functional Trypanosoma cruzi U2AF35 3' untranslated region (UTR)
      (Tc3) or, alternatively, the sequence of the PTP tag, which can be fused to any
      mRNA of interest. Two cell lines were created, single-marker Tc3 (smTc3) and
      smPTP, which conditionally express Tc3 and PTP double-stranded RNA (dsRNA),
      respectively. The system depends on manipulating both alleles of the gene of
      interest so that cells exclusively express the target mRNA as a fusion to one of
      these heterologous sequences. We generated allele integration vectors in which
      the C-terminal part of a gene's coding sequence can be fused to either
      heterologous sequence in a single cloning step. We first tested this system with
      CITFA7, which encodes a well-characterized subunit of the class I transcription
      factor A (CITFA), an essential factor for transcription initiation by RNA
      polymerase I. Targeting either Tc3 or PTP fused to the CITFA7 mRNA resulted in
      gene knockdowns that were as efficient and specific as targeting the endogenous
      CITFA7 mRNA. Moreover, application of this system to CITFA1, which could not be
      silenced by established methods, demonstrated that the gene encodes an essential
      CITFA subunit that mediates binding of the transcription factor complex to RNA
      polymerase I promoters. 

PMID- 24728196
TI  - Distinct and redundant roles of protein tyrosine phosphatases Ptp1 and Ptp2 in
      governing the differentiation and pathogenicity of Cryptococcus neoformans.
AB  - Protein tyrosine phosphatases (PTPs) serve as key negative-feedback regulators of
      mitogen-activated protein kinase (MAPK) signaling cascades. However, their roles
      and regulatory mechanisms in human fungal pathogens remain elusive. In this
      study, we characterized the functions of two PTPs, Ptp1 and Ptp2, in Cryptococcus
      neoformans, which causes fatal meningoencephalitis. PTP1 and PTP2 were found to
      be stress-inducible genes, which were controlled by the MAPK Hog1 and the
      transcription factor Atf1. Ptp2 suppressed the hyperphosphorylation of Hog1 and
      was involved in mediating vegetative growth, sexual differentiation, stress
      responses, antifungal drug resistance, and virulence factor regulation through
      the negative-feedback loop of the HOG pathway. In contrast, Ptp1 was not
      essential for Hog1 regulation, despite its Hog1-dependent induction. However, in
      the absence of Ptp2, Ptp1 served as a complementary PTP to control some stress
      responses. In differentiation, Ptp1 acted as a negative regulator, but in a Hog1-
      and Cpk1-independent manner. Additionally, Ptp1 and Ptp2 localized to the cytosol
      but were enriched in the nucleus during the stress response, affecting the
      transient nuclear localization of Hog1. Finally, Ptp1 and Ptp2 played minor and
      major roles, respectively, in the virulence of C. neoformans. Taken together, our
      data suggested that PTPs could be exploited as novel antifungal targets. 

PMID- 24728197
TI  - The basic leucine zipper domain transcription factor Atf1 directly controls Cdc13
      expression and regulates mitotic entry independently of Wee1 and Cdc25 in
      Schizosaccharomyces pombe.
AB  - Progression into mitosis is a major point of regulation in the
      Schizosaccharomyces pombe cell cycle, and its proper control is essential for
      maintenance of genomic stability. Investigation of the G(2)/M progression event
      in S. pombe has revealed the existence of a complex regulatory process that is
      responsible for making the decision to enter mitosis. Newer aspects of this
      regulation are still being revealed. In this paper, we report the discovery of a
      novel mode of regulation of G(2)/M progression in S. pombe. We show that the
      mitogen-activated protein kinase (MAPK)-regulated transcription factor Atf1 is a
      regulator of Cdc13 (mitotic cyclin) transcription and is therefore a prominent
      player in the regulation of mitosis in S. pombe. We have used genetic approaches
      to study the effect of overexpression or deletion of Atf1 on the cell length and
      G(2)/M progression of S. pombe cells. Our results clearly show that Atf1
      overexpression accelerates mitosis, leading to an accumulation of cells with
      shorter lengths. The previously known major regulators of entry into mitosis are
      the Cdc25 phosphatase and the Wee1 kinase, which modulate cyclin-dependent kinase
      (CDK) activity. The significantly striking aspect of our discovery is that Atf1
      mediated G(2)/M progression is independent of both Cdc25 and Wee1. We have shown
      that Atf1 binds to the Cdc13 promoter, leading to activation of Cdc13 expression.
      This leads to enhanced nuclear localization of CDK Cdc2, thereby promoting the
      G(2)/M transition.

PMID- 24728199
TI  - A bio-inspired inner-motile photocatalyst film: a magnetically actuated
      artificial cilia photocatalyst.
AB  - A new type of inner-motile photocatalyst film is explored to enhance
      photocatalytic performance using magnetically actuated artificial cilia. The
      inner-motile photocatalyst film is capable of generating flow and mixing on the
      microscale because it produces a motion similar to that of natural cilia when it
      is subjected to a rotational magnetic field. Compared with traditional
      photocatalyst films, the inner-motile photocatalyst film exhibits the unique
      ability of microfluidic manipulation. It uses an impactful and self-contained
      design to accelerate interior mass transfer and desorption of degradation
      species. Moreover, the special cilia-like structures increase the surface area
      and light absorption. Consequently, the photocatalytic activity of the inner
      motile photocatalyst film is dramatically improved to approximately 3.0 times
      that of the traditional planar film. The inner-motile photocatalyst film also
      exhibits high photocatalytic durability and can be reused several times with
      ease. Furthermore, this feasible yet versatile platform can be extended to other
      photocatalyst systems, such as TiO2, P25, ZnO, and Co3O4 systems, to improve
      their photocatalytic performance. 

PMID- 24728198
TI  - Plasma metabolomic profiling suggests early indications for predisposition to
      latent insulin resistance in children conceived by ICSI.
AB  - BACKGROUND: There have been increasing indications about an epigenetically-based
      elevated predisposition of assisted reproductive technology (ART) offspring to
      insulin resistance, which can lead to an unfavorable cardio-metabolic profile in
      adult life. However, the relevant long-term systematic molecular studies are
      limited, especially for the IntraCytoplasmic Sperm Injection (ICSI) method,
      introduced in 1992. In this study, we carefully defined a group of 42 prepubertal
      ICSI and 42 naturally conceived (NC) children. We assessed differences in their
      metabolic profile based on biochemical measurements, while, for a subgroup,
      plasma metabolomic analysis was also performed, investigating any relevant
      insulin resistance indices. METHODS & RESULTS: Auxological and biochemical
      parameters of 42 6.8+/-2.1 yrs old ICSI-conceived and 42 age-matched controls
      were measured. Significant differences between the groups were determined using
      univariate and multivariate statistics, indicating low urea and low-grade
      inflammation markers (YKL-40, hsCRP) and high triiodothyronine (T3) in ICSI
      children compared to controls. Moreover, plasma metabolomic analysis carried out
      for a subgroup of 10 ICSI- and 10 NC girls using Gas Chromatography-Mass
      Spectrometry (GC-MS) indicated clear differences between the two groups,
      characterized by 36 metabolites linked to obesity, insulin resistance and
      metabolic syndrome. Notably, the distinction between the two girl subgroups was
      accentuated when both their biochemical and metabolomic measurements were
      employed. CONCLUSIONS: The present study contributes a large auxological and
      biochemical dataset of a well-defined group of pre-pubertal ICSI-conceived
      subjects to the research of the ART effect to the offspring's health. Moreover,
      it is the first time that the relevant usefulness of metabolomics was
      investigated. The acquired results are consistent with early insulin resistance
      in ICSI-offspring, paving the way for further systematic investigations. These
      data support that metabolomics may unravel metabolic differences before they
      become clinically or biochemically evident, underlining its utility in the ART
      research.

PMID- 24728200
TI  - A new tubRZ operon involved in the maintenance of the Bacillus sphaericus
      mosquitocidal plasmid pBsph.
AB  - pBsph is a mosquitocidal plasmid first identified from Bacillus sphaericus,
      encoding binary toxins (Bin toxins) that are highly toxic to mosquito larvae.
      This plasmid plays an important role in the maintenance and evolution of the bin
      genes in B. sphaericus. However, little is known about its replication and
      partitioning. Here, we identified a 2.4 kb minimal replicon of pBsph plasmid that
      contained an operon encoding TubR-Bs and TubZ-Bs, each of which was shown to be
      required for plasmid replication. TubR-Bs was shown to be a transcriptional
      repressor of tubRZ-Bs genes and could bind cooperatively to the replication
      origin of eleven 12 bp degenerate repeats in three blocks, and this binding was
      essential for plasmid replication. TubZ-Bs exhibited GTPase activities and
      interacted with TubR-Bs : DNA complex to form a ternary nucleoprotein apparatus.
      Electron and fluorescence microscopy revealed that TubZ-Bs assembled filaments
      both in vitro and in vivo, and two point mutations in TubZ-Bs (T114A and Y260A)
      that severely impaired the GTPase and polymerization activities were found to be
      defective for plasmid maintenance. Further investigation demonstrated that
      overproduction of TubZ-Bs-GFP or its mutant forms significantly reduced the
      stability of pBsph. Taken together, these results suggested that TubR-Bs and TubZ
      Bs are involved in the replication and probably in the partitioning of pBsph
      plasmid, increasing our understanding of the genetic particularity of TubZ
      systems. 

PMID- 24728201
TI  - Analysis of expressed genes of the bacterium 'Candidatus phytoplasma Mali'
      highlights key features of virulence and metabolism.
AB  - 'Candidatus Phytoplasma mali' is a phytopathogenic bacterium of the family
      Acholeplasmataceae assigned to the class Mollicutes. This causative agent of the
      apple proliferation colonizes in Malus domestica the sieve tubes of the plant
      phloem resulting in a range of symptoms such as witches'--broom formation,
      reduced vigor and affecting size and quality of the crop. The disease is
      responsible for strong economical losses in Europe. Although the genome sequence
      of the pathogen is available, there is only limited information on expression of
      selected genes and metabolic key features that have not been examined on the
      transcriptomic or proteomic level so far. This situation is similar to many other
      phytoplasmas. In the work presented here, RNA-Seq and mass spectrometry shotgun
      techniques were applied on tissue samples from Nicotiana occidentalis infected by
      'Ca. P. mali' strain AT providing insights into transcriptome and proteome of the
      pathogen. Data analysis highlights expression of 208 genes including 14 proteins
      located in the terminal inverted repeats of the linear chromosome. Beside a high
      portion of house keeping genes, the recently discussed chaperone GroES/GroEL is
      expressed. Furthermore, gene expression involved in formation of a type IVB and
      of the Sec-dependent secretion system was identified as well as the highly
      expressed putative pathogenicity-related SAP11-like effector protein. Metabolism
      of phytoplasmas depends on the uptake of spermidine/putescine, amino acids, co
      factors, carbohydrates and in particular malate/citrate. The expression of these
      transporters was confirmed and the analysis of the carbohydrate cycle supports
      the suggested alternative energy-providing pathway for phytoplasmas releasing
      acetate and providing ATP. The phylogenetic analyses of malate dehydrogenase and
      acetate kinase in phytoplasmas show a closer relatedness to the Firmicutes in
      comparison to Mycoplasma species indicating an early divergence of the
      Acholeplasmataceae from the Mollicutes.

PMID- 24728203
TI  - Life Support After Brain Death.

PMID- 24728202
TI  - The Barriers to High-Quality Inpatient Pain Management: A Qualitative Study.
AB  - The current literature suggests deficiencies in the quality of acute pain
      management among general medical inpatients. The aim of this qualitative study is
      to identify potential barriers to high-quality acute pain management among
      general medical inpatients at an urban academic medical center during a 2-year
      period. Data are collected using retrospective chart reviews, survey
      questionnaires, and semistructured, open-ended interviews of 40 general medical
      inpatients who have experienced pain during their hospitalization. Our results
      confirm high prevalence and disabling impacts of pain and significant patient-
      and provider-related barriers to high-quality acute pain management. We also
      identify unique system-related barriers such as time delay and pain management
      culture. Efforts to improve the pain management experience of general medical
      inpatients will need to address all these barriers. 

PMID- 24728204
TI  - Pain Management for Persons Living With HIV Disease: Experience With
      Interprofessional Education in Nigeria.
AB  - CONTEXT: Pain management (PM) has not been routinely incorporated into HIV/AIDS
      care and treatment in resource-constrained settings. OBJECTIVES: We describe
      training for multidisciplinary teams tasked with integrating care management into
      HIV clinics to address pain for persons living with HIV in Nigeria. METHODS:
      Education on PM was provided to mixed-disciplinary teams including didactic and
      iterative sessions following home and hospital visits. Participants identified
      challenges and performed group problem solving. RESULTS: HIV trainers identified
      barriers to introducing PM reflecting views of the patient, providers, culture,
      and the health environment. Implementation strategies included (1) building upon
      existing relationships; (2) preliminary advocacy; (3) attention to staff needs;
      and (4) structured data review. CONCLUSION: Implementing PM in Nigerian HIV
      clinics requires recognition of cultural beliefs.

PMID- 24728205
TI  - End-of-Life Issues in UK Medical Schools.
AB  - OBJECTIVE: A descriptive study to determine the current status of end-of-life
      (EOL) issues in UK medical schools. METHODS: A brief questionnaire was mailed to
      the 31 medical schools in the United Kingdom in the spring of 2013. Data analysis
      consisted of frequency distributions. RESULTS: All schools offered some exposure
      to the topic of dying, death and bereavement, and palliative care, although the
      orientation had increased somewhat from an earlier study in 2000. The palliative
      medicine specialist and the nurse specialist in palliative care are the most
      consistent members of the team. Most schools have hospice participation, with
      time spent with a hospice patient increasing over the period. DISCUSSION: Data
      suggest that UK medical schools have addressed EOL issues. These findings should
      have significance for medical schools considering changes in their EOL offerings.

PMID- 24728206
TI  - Atypical stoichiometry for a 3D bimetallic oxalate-based long-range ordered
      magnet exhibiting high proton conductivity.
AB  - The reproducible formation of a 3D oxalate based coordination compound of formula
      (NH4)5[Mn(II)2Cr(III)3(ox)9].10H2O, with an unusual Mn(II)/Cr(III) ratio, is
      presented. The original topology of the anionic network leads to
      antiferromagnetic long-range ordering whereas its guests favour high humidity
      dependent proton conductivity. 

PMID- 24728207
TI  - The spectral diversity of resting-state fluctuations in the human brain.
AB  - In order to assess whole-brain resting-state fluctuations at a wide range of
      frequencies, resting-state fMRI data of 20 healthy subjects were acquired using a
      multiband EPI sequence with a low TR (354 ms) and compared to 20 resting-state
      datasets from standard, high-TR (1800 ms) EPI scans. The spatial distribution of
      fluctuations in various frequency ranges are analyzed along with the spectra of
      the time-series in voxels from different regions of interest. Functional
      connectivity specific to different frequency ranges (<0.1 Hz; 0.1-0.25 Hz; 0.25
      0.75 Hz; 0.75-1.4 Hz) was computed for both the low-TR and (for the two lower
      frequency ranges) the high-TR datasets using bandpass filters. In the low-TR
      data, cortical regions exhibited highest contribution of low-frequency
      fluctuations and the most marked low-frequency peak in the spectrum, while the
      time courses in subcortical grey matter regions as well as the insula were
      strongly contaminated by high-frequency signals. White matter and CSF regions had
      highest contribution of high-frequency fluctuations and a mostly flat power
      spectrum. In the high-TR data, the basic patterns of the low-TR data can be
      recognized, but the high-frequency proportions of the signal fluctuations are
      folded into the low frequency range, thus obfuscating the low-frequency dynamics.
      Regions with higher proportion of high-frequency oscillations in the low-TR data
      showed flatter power spectra in the high-TR data due to aliasing of the high
      frequency signal components, leading to loss of specificity in the signal from
      these regions in high-TR data. Functional connectivity analyses showed that there
      are correlations between resting-state signal fluctuations of distant brain
      regions even at high frequencies, which can be measured using low-TR fMRI. On the
      other hand, in the high-TR data, loss of specificity of measured fluctuations
      leads to lower sensitivity in detecting functional connectivity. This underlines
      the advantages of low-TR EPI sequences for resting-state and potentially also
      task-related fMRI experiments. 

PMID- 24728209
TI  - Mechanisms of charge transfer and redistribution in LaAlO3/SrTiO3 revealed by
      high-energy optical conductivity.
AB  - In condensed matter physics the quasi two-dimensional electron gas at the
      interface of two different insulators, polar LaAlO3 on nonpolar SrTiO3
      (LaAlO3/SrTiO3) is a spectacular and surprising observation. This phenomenon is
      LaAlO3 film thickness dependent and may be explained by the polarization
      catastrophe model, in which a charge transfer of 0.5e(-) from the LaAlO3 film
      into the LaAlO3/SrTiO3 interface is expected. Here we show that in conducting
      samples (>= 4 unit cells of LaAlO3) there is indeed a ~0.5e(-) transfer from
      LaAlO3 into the LaAlO3/SrTiO3 interface by studying the optical conductivity in a
      broad energy range (0.5-35 eV). Surprisingly, in insulating samples (<= 3 unit
      cells of LaAlO3) a redistribution of charges within the polar LaAlO3 sublayers
      (from AlO2 to LaO) as large as ~0.5e(-) is observed, with no charge transfer into
      the interface. Hence, our results reveal the different mechanisms for the
      polarization catastrophe compensation in insulating and conducting LaAlO3/SrTiO3
      interfaces.

PMID- 24728210
TI  - Development and applications of a comprehensive land use classification and map
      for the US.
AB  - Land cover maps reasonably depict areas that are strongly converted by human
      activities, but typically are unable to resolve low-density but widespread
      development patterns. Data products specifically designed to resolve land uses
      complement land cover datasets and likely improve our ability to understand the
      extent and complexity of human modification. Methods for developing a
      comprehensive land use classification system are described, and a map of land use
      for the conterminous United States is presented to reveal what we are doing on
      the land. The comprehensive, detailed and high-resolution dataset was developed
      through spatial analysis of nearly two-dozen publicly-available, national spatial
      datasets--predominantly based on census housing, employment, and infrastructure,
      as well as land cover from satellite imagery. This effort resulted in 79 land use
      classes that fit within five main land use groups: built-up, production,
      recreation, conservation, and water. Key findings from this study are that built
      up areas occupy 13.6% of mainland US, but that the majority of this occurs as low
      density exurban/rural residential (9.1% of the US), while more intensive built-up
      land uses occupy 4.5%. For every acre of urban and suburban residential land,
      there are 0.13 commercial, 0.07 industrial, 0.48 institutional, and 0.29 acres of
      interstates/highways. This database can be used to address a variety of natural
      resource applications, and I provide three examples here: an entropy index of the
      diversity of land uses for smart-growth planning, a power-law scaling of
      metropolitan area population to developed footprint, and identifying potential
      conflict areas by delineating the urban interface.

PMID- 24728211
TI  - Therapeutic concentration of morphine reduces oxidative stress in glioma cell
      line.
AB  - Morphine is a potent analgesic opioid used extensively for pain treatment. During
      the last decade, global consumption grew more than 4-fold. However, molecular
      mechanisms elicited by morphine are not totally understood. Thus, a growing
      literature indicates that there are additional actions to the analgesic effect.
      Previous studies about morphine and oxidative stress are controversial and used
      concentrations outside the range of clinical practice. Therefore, in this study,
      we hypothesized that a therapeutic concentration of morphine (1 MUM) would show a
      protective effect in a traditional model of oxidative stress. We exposed the C6
      glioma cell line to hydrogen peroxide (H2O2) and/or morphine for 24 h and
      evaluated cell viability, lipid peroxidation, and levels of sulfhydryl groups (an
      indicator of the redox state of the cell). Morphine did not prevent the decrease
      in cell viability provoked by H2O2 but partially prevented lipid peroxidation
      caused by 0.0025% H2O2 (a concentration allowing more than 90% cell viability).
      Interestingly, this opioid did not alter the increased levels of sulfhydryl
      groups produced by exposure to 0.0025% H2O2, opening the possibility that
      alternative molecular mechanisms (a direct scavenging activity or the inhibition
      of NAPDH oxidase) may explain the protective effect registered in the lipid
      peroxidation assay. Our results demonstrate, for the first time, that morphine in
      usual analgesic doses may contribute to minimizing oxidative stress in cells of
      glial origin. This study supports the importance of employing concentrations
      similar to those used in clinical practice for a better approximation between
      experimental models and the clinical setting.

PMID- 24728212
TI  - Aspirin plus calcium supplementation to prevent superimposed preeclampsia: a
      randomized trial.
AB  - Preeclampsia is an important cause of maternal and perinatal morbidity and
      mortality. Previous studies have tested calcium supplementation and aspirin
      separately to reduce the incidence of preeclampsia but not the effects of
      combined supplementation. The objective of this study was to investigate the
      effectiveness of aspirin combined with calcium supplementation to prevent
      preeclampsia in women with chronic hypertension. A double-blind, placebo
      controlled randomized clinical trial was carried out at the antenatal clinic of a
      large university hospital in Sao Paulo, SP, Brazil. A total of 49 women with
      chronic hypertension and abnormal uterine artery Doppler at 20-27 weeks gestation
      were randomly assigned to receive placebo (N = 26) or 100 mg aspirin plus 2 g
      calcium (N = 23) daily until delivery. The main outcome of this pilot study was
      development of superimposed preeclampsia. Secondary outcomes were fetal growth
      restriction and preterm birth. The rate of superimposed preeclampsia was 28.6%
      lower among women receiving aspirin plus calcium than in the placebo group (52.2
      vs 73.1%, respectively, P=0.112). The rate of fetal growth restriction was
      reduced by 80.8% in the supplemented group (25 vs 4.8% in the placebo vs
      supplemented groups, respectively; P=0.073). The rate of preterm birth was 33.3%
      in both groups. The combined supplementation of aspirin and calcium starting at
      20-27 weeks of gestation produced a nonsignificant decrease in the incidence of
      superimposed preeclampsia and fetal growth restriction in hypertensive women with
      abnormal uterine artery Doppler.

PMID- 24728213
TI  - Evaluation of Toll-like, chemokine, and integrin receptors on monocytes and
      neutrophils from peripheral blood of septic patients and their correlation with
      clinical outcomes.
AB  - Recognition of pathogens is performed by specific receptors in cells of the
      innate immune system, which may undergo modulation during the continuum of
      clinical manifestations of sepsis. Monocytes and neutrophils play a key role in
      host defense by sensing and destroying microorganisms. This study aimed to
      evaluate the expression of CD14 receptors on monocytes; CD66b and CXCR2 receptors
      on neutrophils; and TLR2, TLR4, TLR5, TLR9, and CD11b receptors on both cell
      types of septic patients. Seventy-seven septic patients (SP) and 40 healthy
      volunteers (HV) were included in the study, and blood samples were collected on
      day zero (D0) and after 7 days of therapy (D7). Evaluation of the cellular
      receptors was carried out by flow cytometry. Expression of CD14 on monocytes and
      of CD11b and CXCR2 on neutrophils from SP was lower than that from HV.
      Conversely, expression of TLR5 on monocytes and neutrophils was higher in SP
      compared with HV. Expression of TLR2 on the surface of neutrophils and that of
      TLR5 on monocytes and neutrophils of SP was lower at D7 than at D0. In addition,
      SP who survived showed reduced expression of TLR2 and TLR4 on the surface of
      neutrophils at D7 compared to D0. Expression of CXCR2 for surviving patients was
      higher at follow-up compared to baseline. We conclude that expression of
      recognition and cell signaling receptors is differentially regulated between SP
      and HV depending on the receptor being evaluated.

PMID- 24728214
TI  - Global microRNA profiles and signaling pathways in the development of cardiac
      hypertrophy.
AB  - Hypertrophy is a major predictor of progressive heart disease and has an adverse
      prognosis. MicroRNAs (miRNAs) that accumulate during the course of cardiac
      hypertrophy may participate in the process. However, the nature of any
      interaction between a hypertrophy-specific signaling pathway and aberrant
      expression of miRNAs remains unclear. In this study, Spague Dawley male rats were
      treated with transverse aortic constriction (TAC) surgery to mimic pathological
      hypertrophy. Hearts were isolated from TAC and sham operated rats (n=5 for each
      group at 5, 10, 15, and 20 days after surgery) for miRNA microarray assay. The
      miRNAs dysexpressed during hypertrophy were further analyzed using a combination
      of bioinformatics algorithms in order to predict possible targets. Increased
      expression of the target genes identified in diverse signaling pathways was also
      analyzed. Two sets of miRNAs were identified, showing different expression
      patterns during hypertrophy. Bioinformatics analysis suggested the miRNAs may
      regulate multiple hypertrophy-specific signaling pathways by targeting the member
      genes and the interaction of miRNA and mRNA might form a network that leads to
      cardiac hypertrophy. In addition, the multifold changes in several miRNAs
      suggested that upregulation of rno-miR-331*, rno-miR-3596b, rno-miR-3557-5p and
      downregulation of rno-miR-10a, miR-221, miR-190, miR-451 could be seen as
      biomarkers of prognosis in clinical therapy of heart failure. This study
      described, for the first time, a potential mechanism of cardiac hypertrophy
      involving multiple signaling pathways that control up- and downregulation of
      miRNAs. It represents a first step in the systematic discovery of miRNA function
      in cardiovascular hypertrophy.

PMID- 24728215
TI  - The expression and phosphorylation of ezrin and merlin in human pancreatic
      cancer.
AB  - Pancreatic carcinoma is the most common pancreatic malignancy and is associated
      with a very poor prognosis. Therefore, new prognostic factors and new treatment
      strategies are clearly needed. In this study, we retrospectively studied the
      levels of phosphorylated ezrin in 19 patients with pancreatic carcinoma by
      immunohistochemical analysis and determined the correlation between protein
      expression, clinicopathological characteristics and prognosis in pancreatic
      adenocarcinoma. We also characterized the phenotype of the overexpression of wild
      type and phosphorylated ezrin and merlin in human pancreatic cancer cell lines. A
      significant correlation between the levels of phosphorylated ezrin 353 and ezrin
      567 and the stage of pancreatic cancer was observed. Moreover, Kaplan-Meier
      analysis revealed that patients with high levels of phosphorylated ezrin had a
      significantly poorer survival rate (P<0.05). In addition, the overexpression of
      wild-type merlin or ezrin inhibited cell proliferation, migration and adhesion.
      However, the overexpression of T567D ezrin, a mutant that mimics permanent
      phosphorylation, promoted the proliferation, adhesion and migration of the
      pancreatic adenocarcinoma cell line SW1990. The overexpression of S518D merlin
      inhibited the growth of SW1990 and did not affect migration or adhesion. These
      results suggest that the phosphorylation of ezrin may contribute to the
      progression of pancreatic carcinoma and that the level of phosphorylated ezrin
      may serve as an adverse prognostic factor for pancreatic carcinoma. 

PMID- 24728216
TI  - Overcautious FDA has lost its way.

PMID- 24728217
TI  - The lighter side.

PMID- 24728218
TI  - The lighter side.

PMID- 24728219
TI  - Peg-interferon plus ribavirin with or without boceprevir or telaprevir for HCV
      genotype 1: a meta-analysis on the role of response predictors.
AB  - BACKGROUND & AIM: To compare the efficacy of pegylated-interferon (Peg-IFN) alpha
      2a or alpha-2b and ribavirin given as dual therapy versus triple therapy (Peg-IFN
      and ribavirin plus boceprevir or telaprevir) in patients with HCV-1 chronic
      hepatitis naive for anti-HCV therapy or relapsers to dual therapy in relation to
      the presence of constitutional, clinical and virological predictors of treatment
      response. METHODS: Included in the meta-analysis were studies meeting these
      criteria: original data from randomized trials on the efficacy of dual versus
      triple therapy in therapy-naive patients or relapsers; at least one primary
      outcome clearly defined: sustained virological response in patients with or
      without rapid virological response (RVR), with genotype 1a or 1b, low or high HCV
      load, IL28-B CC or non-CC genotype, mild or severe fibrosis; odds ratio estimates
      of relative risk (RR) and 95% confidence intervals; English language; and
      published up to the end of June 2013. RESULTS: Seven original studies met the
      inclusion criteria, allowing a meta-analysis on 3,652 patients. Triple therapy
      was more effective than dual, regardless of IL-28B genotype, HCV sub-genotype,
      liver fibrosis, and baseline HCV load. In 1,045 patients who achieved RVR, SVR
      was more frequently achieved with dual therapy (RR = 1.11; p = 0.002) than
      triple. The same results were achieved when only the therapy-naive patients were
      considered. CONCLUSIONS: Triple therapy provides a significantly higher SVR rate
      than dual therapy, but dual therapy obtains a significantly higher SVR rate in
      patients with RVR. The data stress the clinical importance of a 4-week lead-in
      phase in direct-acting antiviral-based treatment.

PMID- 24728220
TI  - [Cutaneous drug reactions imitating dermatoses].
AB  - BACKGROUND: Cutaneous adverse drug reactions are frequent and present with
      heterogenous clinical manifestations. METHODS AND RESULTS: Increasingly, case
      reports describe drug reactions which mimic dermatoses, although exact data on
      prevalence are missing. Psoriasiform, lichenoid and pityriasiform exanthems are
      most frequent. The differentiation of these variants from the respective
      authentic dermatoses is difficult and only a few clinical and histological
      criteria are helpful. Other dermatoses like lupus erythematosus or bullous
      autoimmune dermatoses (pemphigus vulgaris, bullous pemphigoid) can be induced by
      drugs as well. These drug-triggered variations are classified as distinct
      subclasses of the respective dermatosis. CONCLUSIONS: Exact history and
      evaluation of the clinical course are essential for the diagnosis of drug
      reactions mimicking dermatoses and present an important challenge for the
      clinician. A clear-cut differentiation between the genuine dermatosis and its
      drug-driven simulator is not always possible.

PMID- 24728221
TI  - Vanadyl complexes bearing bi-dentate phenoxyimine ligands: synthesis, structural
      studies and ethylene polymerization capability.
AB  - Reaction of [VO(OnPr)3] with the Schiff bases 3,5-(tBu)2-2-OH-C6H2CH(N(x-OR
      C6H4)) (R = Me; x = 2, L(1)H; x = 3, L(2)H; x = 4, L(3)H; R = Et (L(4)H), CF3
      (L(5)H), Ph (L(6)H)) or 4-methyl-3-(R)-2-(OH)-C6H4C[double bond, length as m
      dash]N(2'-(2''-(OR1)C6H4)C6H4) (R = adamantyl, R(1) = Ph (L(7)H) or R = C(Me)2Ph,
      R(1) = Ph (L(8)H)) afforded the bis(chelate) vanadium(iv) complexes [VO(L(n))2]
      (n = 1 (1.2MeCN); n = 2 (2); n = 3 (3.2MeCN); n = 4 (4); n = 5 (5); n = 6 (6); n
      = 6, (7.1.5MeCN); n = 7, (8); n = 8, (9)); in the case of L(6)H, the oxo-bridged
      vanadium(v) complexes [VO(MU-O)(L(6))]2 (10) was also isolated. By contrast,
      interaction of 4-methyl-3-(R)-2-(OH)-C6H4C[double bond, length as m-dash]N(2'
      (2''-(OR1)C6H4)C6H4) (R = adamantyl, R(1) = Me (L(9)H); R = tBu, R(1) = Me
      (L(10)H); R = C(Me)2Ph, R(1) = Me (L(11)H)) with [VO(OnPr)3] led to the isolation
      of the dinuclear complexes [VO(MU-OH)(MU-OnPr)(L(n))]2 (n = 9, (.4MeCN); 10,
      (12); 11, (13)), respectively. The molecular structures of 1 to 13 are reported.
      All complexes have been screened as pre-catalysts for the polymerization of
      ethylene in the presence of the co-catalyst diethylaluminium chloride (DEAC) with
      or without ethyltrichloroacetate (ETA) present at 1 or 10 bar of ethylene. Under
      high pressure, all pre-catalysts exhibited high activity and afforded high
      molecular weight (Mw ~ 200 000 to 675 000 g mol(-1)), linear polyethylene with
      activities (in the presence of ETA) in the range 4960-16 400 g mmol(-1) h(-1); at
      one bar, the products were generally of lower molecular weight. The use of
      methylaluminoxane (MAO) or modified MAO (MMAO) as co-catalyst led to trace or
      poor (<=110 g mmol(-1) h(-1)) activity, respectively.

PMID- 24728222
TI  - Dissecting variation in biomass conversion factors across China's forests:
      implications for biomass and carbon accounting.
AB  - Biomass conversion factors (BCFs, defined as the ratios of tree components (i.e.
      stem, branch, foliage and root), as well as aboveground and whole biomass of
      trees to growing stock volume, Mg m-3) are considered as important parameters in
      large-scale forest biomass carbon estimation. To date, knowledge of possible
      sources of the variation in BCFs is still limited at large scales. Using our
      compiled forest biomass dataset of China, we presented forest type-specific
      values of BCFs, and examined the variation in BCFs in relation to forest type,
      stand development and environmental factors (climate and soil fertility). BCFs
      exhibited remarkable variation across forest types, and also were significantly
      related to stand development (especially growing stock volume). BCFs (except Stem
      BCF) had significant relationships with mean annual temperature (MAT) and mean
      annual precipitation (MAP) (P<0.001). Climatic data (MAT and MAP) collectively
      explained 10.0-25.0% of the variation in BCFs (except Stem BCFs). Moreover,
      stronger climatic effects were found on BCFs for functional components (i.e.
      branch, foliage and root) than BCFs for combined components (i.e. aboveground
      section and whole trees). A general trend for BCFs was observed to decrease and
      then increase from low to high soil fertility. When qualitative soil fertility
      and climatic data (MAT and MAP) were combined, they explained 14.1-29.7% of the
      variation in in BCFs (except Stem BCFs), adding only 4.1-4.9% than climatic data
      used. Therefore, to reduce the uncertainty induced by BCFs in forest carbon
      estimates, we should apply values of BCFs for a specified forest type, and also
      consider climatic and edaphic effects, especially climatic effect, in developing
      predictive models of BCFs (except Stem BCF). 

PMID- 24728223
TI  - Thin film complementary metal oxide semiconductor (CMOS) device using a single
      step deposition of the channel layer.
AB  - We report, for the first time, the use of a single step deposition of
      semiconductor channel layer to simultaneously achieve both n- and p-type
      transport in transparent oxide thin film transistors (TFTs). This effect is
      achieved by controlling the concentration of hydroxyl groups (OH-groups) in the
      underlying gate dielectrics. The semiconducting tin oxide layer was deposited at
      room temperature, and the maximum device fabrication temperature was 350  degrees
      C. Both n and p-type TFTs showed fairly comparable performance. A functional CMOS
      inverter was fabricated using this novel scheme, indicating the potential use of
      our approach for various practical applications.

PMID- 24728228
TI  - Amino group binding peptide aptamers with double disulphide-bridged loops
      selected by in vitro selection using cDNA display.
AB  - Peptide aptamers that specifically bind to the amino group on a solid-phase were
      screened by in vitro selection using the cDNA display method. The identified
      peptides have a unique structure containing two cyclic loops with disulphide
      bonds and a linkage region, which were indispensable for molecular recognition. 

PMID- 24728227
TI  - Functionalized amphipols: a versatile toolbox suitable for applications of
      membrane proteins in synthetic biology.
AB  - Amphipols are amphipathic polymers that stabilize membrane proteins isolated from
      their native membrane. They have been functionalized with various chemical groups
      in the past years for protein labeling and protein immobilization. This large
      toolbox of functionalized amphipols combined with their interesting physico
      chemical properties give opportunities to selectively add multiple
      functionalities to membrane proteins and to tune them according to the needs.
      This unique combination of properties makes them one of the most versatile
      strategies available today for exploiting membrane proteins onto surfaces for
      various applications in synthetic biology. This review summarizes the properties
      of functionalized amphipols suitable for synthetic biology approaches. 

PMID- 24728229
TI  - A comparison of hearing results following stapedotomy under local versus general
      anesthesia.
AB  - Advances in operative technique, instrumentation, and prosthesis design in
      otosclerosis surgery continue since Shea performed the first successful surgery.
      This is the first analysis to specifically compare post-operative hearing
      outcomes following stapedotomy surgery performed under local versus general
      anesthesia. Hearing outcomes were further stratified by comparing conventional
      perforator and Er:YAG laser ablation perforation techniques. Pre- and post
      operative audiograms were retrospectively analyzed together with the method of
      anesthesia and the perforation technique for all patients with otosclerosis who
      underwent stapedotomy between 1998 and 2007. Pre-operative individual standard
      audiometry frequency thresholds (IFTs), air (AC) and bone conduction pure tone
      averages (PTA), and air bone gaps (ABG) were compared against post-operative
      results. Differences between pre- and post-operative PTAs and ABGs were compared
      between patients who received stapedotomy under local versus general anesthesia,
      as well as for patients who underwent conventional versus Er:YAG laser ablation
      perforations. Eighty-six patients were identified of which 24 % (n = 21) received
      local and 76 % (n = 65) received general anesthesia. Post-operative audiograms
      were available for 84 and 48 patients, respectively. Significant improvements
      were seen across all groups for standard 4-frequency AC-PTA and ABG and for IFTs
      up to 3 kHz. No significant difference was seen for IFTs between 4 and 6 kHz. A
      significant decline in post-operative hearing thresholds was seen at 8 kHz.
      Significant improvements in PTA and ABG were seen for all groups. There was a
      trend toward general compared to local anesthesia post-operative hearing results
      furthermore in combination with conventional perforation technique then with
      laser technique.

PMID- 24728231
TI  - Lingua-epiglottis position predicts glossopharyngeal obstruction in patients with
      obstructive sleep apnea hypopnea syndrome.
AB  - The objective of the study was to investigate the relationship between lingua
      epiglottis position and glossopharyngeal obstruction in patients with obstructive
      sleep apnea hypopnea syndrome (OSAHS). One hundred and four patients with OSAHS
      diagnosed by polysomnography (PSG) were enrolled. Lingua-epiglottis position was
      visualized using endoscopy and classified into three types. Spiral CT imaging of
      the upper respiratory tract was performed to measure the cross-sectional area and
      inner diameter of the glossopharyngeal airway. The PSG was repeated after
      nasopharyngeal tube insertion (NPT-PSG). The NPT-PSG results, CT-measured data
      and incidence of stenosis were compared among the different lingua-epiglottis
      position groups. Obstructive sleep apnea hypopnea syndrome patients with
      different lingua-epiglottis positions had similar demographics. As lingua
      epiglottis position type varied from type I to type III, cross-sectional area and
      inner diameter of the glossopharyngeal area decreased, glossopharyngeal airway
      stenosis rate increased, and apnea hypopnea index measured by NPT-PSG increased.
      The lowest oxygen saturation decreased. Lingua-epiglottis position was
      significantly related to glossopharyngeal obstruction. Lingua-epiglottis position
      should be used in clinical practice for the preliminary assessment of
      glossopharyngeal obstruction. 

PMID- 24728230
TI  - Prognostic factors of quality of life after transoral laser microsurgery for
      laryngeal cancer.
AB  - We aimed to evaluate factors influencing quality of life (QOL) after transoral
      laser microsurgery (TLM) of laryngeal cancer. Four hundred and one consecutive
      disease-free patients were evaluated 1 year after treatment using the University
      of Washington-QOL v4, the SF-12 (short form of SF-36), and a questionnaire about
      self-rated health status. The importance of age, gender, tumor location, tumor
      size, tumor stage, neck dissection and adjuvant treatment were evaluated. One
      year after TLM patients had a good QOL, with only 6 % of patients reporting a
      worsening in their health status. Radiation therapy (p = 0.000) and neck
      dissection (p = 0.000) were negative factors for disease-specific QOL, whereas
      age >= 70 (p = 0.01) was a positive independent factor for mental score of SF-12.
      Speech was negatively influenced by tumor size (p = 0.001) as was swallowing by
      age (p = 0.001) and postoperative radiation (p = 0.000). Patients treated with
      TLM present a good QOL 1 year after surgery. Radiation and neck dissection
      negatively impact QOL. Elderly patients cope better with their disabilities.

PMID- 24728232
TI  - Fatigue during an episode of benign paroxysmal positional vertigo.
AB  - Fatigue is characterized by weariness unrelated to exertion levels. It has been
      reported in chronic neurological diseases such as multiple sclerosis, Parkinson
      disease and stroke. Patients with benign paroxysmal positional vertigo (BPPV)
      often complain about fatigue during a vertigo attack. No attention has been paid
      to this symptom in the literature so far. We were interested to evaluate the
      frequency and factors influencing fatigue in BPPV. Patients treated for
      idiopathic BPPV during the years 2011-2012 were prospectively evaluated for the
      presence of fatigue. During the first visit, patients were asked to complete two
      questionnaires based on their experience during the last week: the Fatigue
      severity scale and the Hospital anxiety and depression scale. Patients'
      demographic data and BPPV characteristics were registered. Among 172 patients
      treated for BPPV, 40 (23.2 %) reported fatigue. The mean fatigue score was 4.73
      +/- 1.98 indicating moderate fatigue. No correlation was found between fatigue
      and anxiety or fatigue and depression. Fatigue scores were inversely related to
      age (r = -0.36, p = 0.020) and were not dependent on the type of BPPV, its
      recurrence, background diseases, gender, duration of vertigo or the presence of
      autonomic symptoms. Moderate fatigue is quite common during an attack of BPPV. It
      seems to be a genuine symptom of the entity that might worsen patients' distress.
      For severe or persistent fatigue treatment with fatigue relieving drugs such as
      amantadine, methylphenidate or modafinil could be tried in the future.

PMID- 24728234
TI  - Direct conversion of multilayer molybdenum trioxide to nanorods as
      multifunctional electrodes in lithium-ion batteries.
AB  - In this study we prepared molybdenum trioxide (MoO3) nanorods having average
      lengths of 0.5-1.5 MUm and widths of approximately 100-200 nm through a one-step
      mechanical break-down process involving favorable fracturing along the crystal
      direction. We controlled the dimensions of the as-prepared nanorods by applying
      various imposing times (15-90 min). The nanorods prepared over a reaction time of
      90 min were, on average, much shorter and narrower relative to those obtained
      over 30 min. Evaluations of lithium-ion storage properties revealed that the
      electrochemical performance of these nanorods was much better than that of bulk
      materials. As cathodes, the nanorods could deliver a high specific capacity (>315
      mA h g(-1)) with losses of less than 2% in the first cycle at a rate of 30 mA g(
      1); as anodes, the specific capacity was 800 mA h g(-1) at a rate of 50 mA g(-1).
      Relative to alpha-MoO3 microparticles, these nanorods displayed significantly
      enhanced lithium-ion storage properties with higher reversible capacities and
      better rate performance, presumably because their much shorter diffusion lengths
      and higher specific surface areas allowed more-efficient insertion/deinsertion of
      lithium ions during the charge/discharge process. Accordingly, enhanced physical
      and/or chemical properties can be obtained through appropriate nanostructuring of
      materials. 

PMID- 24728235
TI  - A two-dimensional pooling strategy for rare variant detection on next-generation
      sequencing platforms.
AB  - We describe a method for pooling and sequencing DNA from a large number of
      individual samples while preserving information regarding sample identity. DNA
      from 576 individuals was arranged into four 12 row by 12 column matrices and then
      pooled by row and by column resulting in 96 total pools with 12 individuals in
      each pool. Pooling of DNA was carried out in a two-dimensional fashion, such that
      DNA from each individual is present in exactly one row pool and exactly one
      column pool. By considering the variants observed in the rows and columns of a
      matrix we are able to trace rare variants back to the specific individuals that
      carry them. The pooled DNA samples were enriched over a 250 kb region previously
      identified by GWAS to significantly predispose individuals to lung cancer. All 96
      pools (12 row and 12 column pools from 4 matrices) were barcoded and sequenced on
      an Illumina HiSeq 2000 instrument with an average depth of coverage greater than
      4,000*. Verification based on Ion PGM sequencing confirmed the presence of 91.4%
      of confidently classified SNVs assayed. In this way, each individual sample is
      sequenced in multiple pools providing more accurate variant calling than a single
      pool or a multiplexed approach. This provides a powerful method for rare variant
      detection in regions of interest at a reduced cost to the researcher. 

PMID- 24728233
TI  - Persistence, seasonal dynamics and pathogenic potential of Vibrio communities
      from Pacific oyster hemolymph.
AB  - Bacteria of the genus Vibrio occur at a continuum from free-living to symbiotic
      life forms, including opportunists and pathogens, that can contribute to severe
      diseases, for instance summer mortality events of Pacific oysters Crassostrea
      gigas. While most studies focused on Vibrio isolated from moribund oysters during
      mortality outbreaks, investigations of the Vibrio community in healthy oysters
      are rare. Therefore, we characterized the persistence, diversity, seasonal
      dynamics, and pathogenicity of the Vibrio community isolated from healthy Pacific
      oysters. In a reciprocal transplant experiment we repeatedly sampled hemolymph
      from adult Pacific oysters to differentiate population from site-specific effects
      during six months of in situ incubation in the field. We characterized virulence
      phenotypes and genomic diversity based on multilocus sequence typing in a total
      of 70 Vibrio strains. Based on controlled infection experiments we could show
      that strains with the ability to colonize healthy adult oysters can also have the
      potential to induce high mortality rates on larvae. Diversity and abundance of
      Vibrio varied significantly over time with highest values during and after
      spawning season. Vibrio communities from transplanted and stationary oysters
      converged over time, indicating that communities were not population specific,
      but rather assemble from the surrounding environment forming communities, some of
      which can persist over longer periods. 

PMID- 24728236
TI  - Micro-environment causes reversible changes in DNA methylation and mRNA
      expression profiles in patient-derived glioma stem cells.
AB  - In vitro and in vivo models are widely used in cancer research. Characterizing
      the similarities and differences between a patient's tumor and corresponding in
      vitro and in vivo models is important for understanding the potential clinical
      relevance of experimental data generated with these models. Towards this aim, we
      analyzed the genomic aberrations, DNA methylation and transcriptome profiles of
      five parental tumors and their matched in vitro isolated glioma stem cell (GSC)
      lines and xenografts generated from these same GSCs using high-resolution
      platforms. We observed that the methylation and transcriptome profiles of in
      vitro GSCs were significantly different from their corresponding xenografts,
      which were actually more similar to their original parental tumors. This points
      to the potentially critical role of the brain microenvironment in influencing
      methylation and transcriptional patterns of GSCs. Consistent with this
      possibility, ex vivo cultured GSCs isolated from xenografts showed a tendency to
      return to their initial in vitro states even after a short time in culture,
      supporting a rapid dynamic adaptation to the in vitro microenvironment. These
      results show that methylation and transcriptome profiles are highly dependent on
      the microenvironment and growth in orthotopic sites partially reverse the changes
      caused by in vitro culturing. 

PMID- 24728237
TI  - Morbidity due trauma in children of the community of Paraisopolis, Sao Paulo,
      Brazil.
AB  - OBJECTIVE: To identify the factors that determine unintentional injuries in
      children living in the community of Paraisopolis, in the city of Sao Paulo,
      Brazil. METHODS: A cross-sectional and non-controlled study. Data collected
      during 4 consecutive months through questionnaires filled out for the Einstein
      Program in Paraisopolis Community included identification of the patient and
      his/her family, scholarity level, housing conditions, storage of hazardous
      products, access to the streets and concrete slab ceilings, supervision, and
      trauma mechanism involved. The observed data were treated as absolute and
      relative frequencies; chi(2), Fisher's exact test, Student's t test, and Mann
      Whitney's tests were implemented, with a significance level of 5% (p<0.05).
      RESULTS: A total of 1,490 questionnaires were analyzed. There was a predominance
      of trauma within boys (59.6%) and the medium age was 5.2 years. The predominant
      educational level of the parents was incomplete junior school education. The main
      caregiver identified was the mother (69.4%). Among the children that suffered
      trauma, 56.4% belonged to large families (>= 6 people), lived in houses up to
      three rooms, and a family income up to R$ 1,000.00 (76.6%). Easy access to
      hazardous materials was considerable and free access to concrete slab ceilings
      was reported in 92.8% of the cases. The main trauma mechanisms were falls and
      burns. In this study, the child victim of a fall was aged under 5 years.
      CONCLUSION: Small children that live in a hazardous environment have a
      significant tendency to suffering trauma.

PMID- 24728238
TI  - Oral health promotion in early childhood: age of joining preventive program and
      behavioral aspects.
AB  - OBJECTIVE: To analyze the interference of age in the entrance into a public
      dental care program for infants as well as family behavioral aspects about tooth
      decay experience in children 0 to 4 years old. METHODS: Cross-sectional study
      involving 465 children who were divided into 3 groups: infants whose mothers
      joined the program during pregnancy (n=50); infants enrolled in the program
      during the first year of life (n=230); and infants enrolled in the program
      between 13 and 18 months old (n=185). The chi(2) and Kruskal-Walis tests (95%
      confidence interval) were used to assess the relationship among variables.
      RESULTS: There was an association between the age of entrance in the programs and
      dental caries (p<0.001). A lower prevalence was seen in infants whose mothers
      joined the program during pregnancy, and among those infants enrolled in the
      program during the first year of life. The same low prevalence occurred in
      relation to mothers' commitment to attend follow-up visits with their infants,
      cariogenic diet, nighttime oral care, duration of night feeding and parents'
      educational level (p<0.001). Unfavorable socioeconomic conditions (p>0.05) and
      daily oral care (p=0.214) were common variables in the groups with 99% of
      occurrence. Commitment to attend follow-up visits, nighttime oral care and
      parents' educational level (p>0.05) were considered protective factors for dental
      caries. Cariogenic diet and night feeding were determinant factors to the
      appearance of dental caries. CONCLUSION: To promote children oral health it is
      essential to enroll children in oral health programs and adopt healthy habits as
      early as possible, besides the adherence of the child to their parents' advice.

PMID- 24728239
TI  - Influence of assessment site in measuring transcutaneous bilirubin.
AB  - OBJECTIVE: To investigate the influence of the site of measurement of
      transcutaneous bilirubin (forehead or sternum) in reproducibility of results as
      compared to plasma bilirubin. METHODS: A cohort study including 58 term newborns
      with no hemolytic disease. Transcutaneous measurements were performed on the
      forehead (halfway between the headline and the glabella, from the left toward the
      right side, making consecutive determinations, one-centimeter apart) and the
      sternum (five measurements, from the suprasternal notch to the xiphoid process
      with consecutive determinations, one-centimeter apart) using Bilicheck(r)
      (SpectRx Inc, Norcross, Georgia, USA). The correlation and agreement between both
      methods and plasma bilirubin were calculated. RESULTS: There was a strong linear
      correlation between both determinations of serum bilirubin at the forehead and
      sternum (r=0.704; p<0.01 and r=0.653; p<0.01, respectively). There was
      correspondence of the mean values of transcutaneous bilirubin measured on the
      sternum (9.9 +/- 2.2mg/dL) compared to plasma levels (10.2 +/- 1.7 mg/dL), but
      both differ from the values measured on the forehead (8.6 +/- 2 .0mg/dL), p<0.05.
      CONCLUSION: In newborn term infants with no hemolytic disease, measuring of
      transcutaneous bilirubin on the sternum had higher accuracy as compared to serum
      bilirubin measurement on the forehead.

PMID- 24728240
TI  - Premalignant and malignant lesions in endometrial polyps in patients undergoing
      hysteroscopic polypectomy.
AB  - OBJECTIVE: To evaluate the incidence of premalignant lesions and cancer in
      endometrial polyps, in patients undergoing hysteroscopic polypectomy. METHODS:
      The results of 1,020 pathological examinations of patients submitted to
      hysteroscopic polypectomy were analyzed, as well as their diagnostic and surgical
      hysteroscopy findings. As to their menstrual status, 295 (28.9%) patients were in
      menacme. Of the total, 193 (65.4%) presented abnormal uterine bleeding, and 102
      (34.6%) were asymptomatic with altered endometrial echo on transvaginal
      ultrasound. Out of 725 (71.1%) postmenopausal patients, 171 (23.6%) were
      symptomatic (abnormal uterine bleeding), and 554 (76.4%) were asymptomatic with
      endometrial echo >5.0mm. RESULTS: Twenty-one (2.0%) patients presented
      premalignant lesions in the polyps, 13 had simple glandular hyperplasia, of which
      5 had no atypia, and eight presented atypia. Eight polyps presented focal area of
      complex hyperplasia: 4 with atypia and 4 without lesions. Cancer was diagnosed in
      5 (0.5%) polyps. Of the 21 polyps that harbored premalignant lesions, 12 were
      interpreted as benign in diagnostic and surgical hysteroscopy. Of the polyps with
      cancer, 4 were also histeroscopically interpreted as normal. CONCLUSION:
      Symptomatic polyps in menacme and in all postmenopausal women should be resected
      and submitted to histopathological examination, since they may have a benign
      aspect, even when harboring areas of cellular atypia or cancer.

PMID- 24728241
TI  - Parturient perineal distensibility tolerance assessed by EPI-NO: an observational
      study.
AB  - OBJECTIVE: To determine how parturient women tolerate the use of a perineal
      distensibility assessment technique using the EPI-NO device. METHODS: An
      observational study with a total of 227 full-term parturient women was performed.
      During the evaluation with EPI-NO, parturient patients were asked about their
      sensation of discomfort. The degree of discomfort was measured using the Visual
      Analogue Scale, with a score from zero to 10. The Mann-Whitney test was applied
      to assess perineal distensibility measured by EPI-NO and the degree of discomfort
      caused by the test according to parity. The relation between perineal
      distensibility and discomfort was analyzed by using the Spearman correlation test
      (r). RESULTS: The test with EPI-NO caused only slight discomfort (mean Visual
      Analogue Scale of 3.8), and primiparous women reported significantly greater
      discomfort (mean Visual Analogue Scale of 4.5) than did multiparous (mean Visual
      Analogue Scale=3.1), with p<0.001 women. A negative correlation was observed, in
      other words, the greater the perineal distensibility on the EPI-NO, the lower the
      pain reported by the patients (r=-0.424; p<0.001). CONCLUSION: The assessment of
      perineal distensibility with EPI-NO was well tolerated by the parturient women.

PMID- 24728242
TI  - Implementation of vertical clinical pharmacist service on venous thromboembolism
      prophylaxis in hospitalized medical patients.
AB  - OBJECTIVE: To describe the vertical clinical pharmacist service's interventions
      in prevention of venous thromboembolism. METHODS: This prospective study was done
      at a private hospital. From January to May 2012, the clinical pharmacist
      evaluated medical patients without prophylaxis for thromboembolism. If the
      patient fulfilled criteria for thromboembolism and did not have
      contraindications, the clinical pharmacist suggested inclusion of pharmacologic
      agents and/or mechanical methods for venous thromboembolism prevention. In
      addition, the appropriate dose, route of administration, duplicity and
      replacement of the drug were suggested. RESULTS: We evaluated 9,000 hospitalized
      medical patients and carried out 77 pharmaceutical interventions. A total of 71
      cases (92.21%) adhered to treatment so that non-adherence occurred in 6 cases
      (7.79%). In 25 cases pharmacologic agents were included and in 20 cases
      mechanical prophylaxis. Dose adjustments, route, frequency, duplicity and
      replacement made up 32 cases. CONCLUSION: The vertical clinical pharmacist
      service included the prophylaxis for venous thromboembolism and promotion of
      appropriate use of medicines in the hospital.

PMID- 24728243
TI  - Prevalence of sexually transmitted diseases in female athletes in Sao Paulo,
      Brazil.
AB  - OBJECTIVE: To determine the prevalence of sexually transmitted diseases in female
      athletes. METHODS: An observational, cross-sectional study was conducted
      including 50 female athletes with mean age of 20 +/- 3 years. Colposcopy, pap
      smear, and polymerase chain reaction for Chlamydia trachomatis, human
      papillomavirus and Neisseria gonorrhoeae were performed. Blood samples were
      collected to test for the human immunodeficiency virus, syphilis, hepatitis B and
      C. The athletes presenting clinical diseases or conditions identifiable by
      laboratory tests were treated and followed up in the unit. RESULTS: Forty-six
      percent of the participants were unaware of sexually transmitted diseases. The
      prevalence of sexually transmitted diseases among athletes was 48% (24 cases).
      Human papillomavirus was the most frequent agent (44%). Considering the human
      papillomavirus genotypes, subtype 16 was the most prevalent (53%), followed by 11
      6 (22%) and 18 (13%). Two athletes tested positive for C. trachomatis. There were
      no cases diagnosed of infection by N. gonorrhoeae, syphilis, hepatitis B,
      hepatitis C and human immunodeficiency virus. However, only 26 athletes had been
      vaccinated for hepatitis B. CONCLUSION: The prevalence of sexually transmitted
      diseases in female athletes was high. Primary prevention measures (hepatitis B
      and human papillomavirus vaccination) and secondary (serology, pap smears) must
      be offered to this specific group of women. The matter should be further
      approached in sports.

PMID- 24728244
TI  - Use of rituximab as a treatment for systemic lupus erythematosus: retrospective
      review.
AB  - OBJECTIVE: To report the experience in three Brazilian institutions with the use
      of rituximab in patients with different clinical forms of lupus erythematosus
      systemic in activity. METHODS: The study consisted of a sample of 17 patients
      with LES, who were already being treated, but that at some stage of the disease
      showed refractory symptoms. The patients were subdivided into groups according to
      the clinical manifestation, and the responses for the use of rituximab were rated
      as complete, partial or no response. Data were collected through a spreadsheet,
      and used specific parameters for each group. The treatment was carried on by
      using therapeutic dose of 1g, and repeating the infusion within an interval of 15
      days. RESULTS: The clinical responses to rituximab of the group only
      hematological and of the group only osteoarticular were complete in all cases. In
      the renal group there was a clinical complete response, two partial and one
      absent. In the renal and hematological group complete response, there was one
      death and a missing response. The pulmonary group presented a complete response
      and two partial. CONCLUSION: The present study demonstrated that rituximab can
      bring benefits to patients with lupus erythematosus systemic, with good
      tolerability and mild side effects; it presented, however, variable response
      according to the system affected.

PMID- 24728245
TI  - Analysis of oxybutynin treatment for hyperhidrosis in patients aged over 40
      years.
AB  - OBJECTIVE: Our aim was to analyze the effectiveness of oxybutynin for
      hyperhidrosis treatment in patients over 40 years. METHODS: Eighty-seven patients
      aged over 40 years were divided into two groups. One group consisted of 48
      (55.2%) patients aged between 40 and 49 years, and another was composed of 39
      (44.8%) patients aged over 50 years (50 to 74 years). A comparative analysis of
      Quality of Life and level of hyperhidrosis between the groups was carried out 6
      weeks after a protocol treatment with oxybutynin. A validated clinical
      questionnaire was used for evaluation. RESULTS: In the younger age group, 75% of
      patients referred a "partial" or "great" improvement in level of hyperhidrosis
      after treatment. This number was particularly impressive in patients over 50
      years, in which 87.2% of the cases demonstrated similar levels of improvement.
      Over 77% of patients in both groups demonstrated improvement in Quality of Life.
      Excellent outcomes were observed in older patients, in which 87.1% of patients
      presented "slightly better" (41%) or "much better" (46.1%) improvement.
      CONCLUSION: Patients aged over 40 years with hyperhidrosis presented excellent
      results after oxybutynin treatment. These outcomes were particularly impressive
      in the age group over 50 years, in which most patients had significant
      improvement in Quality of Life and in level of hyperhidrosis.

PMID- 24728246
TI  - Stages of changes for fruit and vegetable intake and their relation to the
      nutritional status of undergraduate students.
AB  - OBJECTIVE: To assess the nutritional and dietetic profile of freshman Nutrition
      undergraduate students, and its association with stages of changes
      (Transtheoretical Model) for fruit and vegetable intake. METHODS: Demographic
      (age and gender), anthropometric (body mass index and waist circumference) and
      nutritional (pattern of fruit and vegetable intake) data were obtained. The
      Transtheoretical Model was used to identify the stages of change for fruit and
      vegetable intake. Food consumption was assessed with a questionnaire developed by
      the Ministry of Health. The significance level considered for all statistical
      tests was 0.05 (p<0.05). RESULTS: From 433 eligible students, anthropometric
      measurements were taken from 219 (50.6%), and 299 (69%) underwent food intake
      evaluation. The sample included undergraduate students with a low frequency of
      adequate fruit and vegetables intake (29.8%), being the majority (64.9%) of them
      classified as at the preparation stage to increase the intake of these food
      groups. Prevalence of adequate fruit and vegetables intake was higher among
      students at the action/maintenance stages (83.3%) compared to those at the
      precontemplation/contemplation (18.3%) and at the preparation stages (32.0%).
      Students at the preparation stage presented the highest medians for body mass
      index (p=0.004) and waist circumference (p=0.039) compared to those at the
      precontemplation/contemplation stages. There was no association between fruit and
      vegetables intake and the presence of overweight or abdominal obesity (p=0.373).
      CONCLUSION: This instrument is effective to predict the food intake and, even
      among aware individuals and ready to change their food behavior, the prevalence
      of nutritional risk is high.

PMID- 24728247
TI  - Effectiveness of exercise at workplace in physical fitness: uncontrolled
      randomized study.
AB  - OBJECTIVE: To investigate the effectiveness of workplace exercise for employee
      health by means of health-related physical activity components. METHODS: A
      randomized uncontrolled study with 20 workers was carried out during three months
      to evaluate a workplace exercise program. The selected outcomes were flexibility,
      body mass, fat percentage, lean mass, blood pressure, and heart rate. For
      statistical analysis, the paired t test and the intent-to-treat analysis were
      used. RESULTS: There was a significant increase in weight, fat percentage, blood
      pressure, and heart rate. However the clinical significance was 10% in the size
      of the effect. CONCLUSION: The changes verified in the outcomes analyzed were not
      significant; the variables are within normality ranges proposed by academic
      organizations.

PMID- 24728248
TI  - Is there any relation between anthropometric indices and decrease in seminal
      parameters?
AB  - OBJECTIVE: To investigate the influence of anthropometric indices on seminal
      parameters. METHODS: Men who underwent treatment for conjugal infertility during
      the period of October, 2011, to March, 2012, were randomly selected. Patients
      with any prior diseases related to sperm alterations were excluded. Patients were
      submitted to an anthropometric evaluation to obtain body mass index, and the
      seminal analysis was made through a spermogram. Two anthropometric methods of
      classification were used: body mass index (normal and altered) and abdominal
      circumference (<94 cm and >94 cm). Data were analyzed by statistical tests.
      RESULTS: The group with the altered body mass index presented lower volumes of
      ejaculated volume and a larger percentage of patients with abdominal
      circumference <94 cm presented with progressive forms of spermatozoa below
      reference values. However, in the statistical tests, there was no significant
      difference. CONCLUSION: No significant difference was found in the sperm quality
      relative to the body mass index or abdominal circumference.

PMID- 24728249
TI  - Coaching leadership: leaders' and followers' perception assessment questionnaires
      in nursing.
AB  - OBJECTIVE: To describe the development, content analysis, and reliability of two
      questionnaires to assess the perception of nurse leaders, nurse technicians, and
      licensed practical nurses - coached in the practice of leadership and the
      relation with the dimensions of the coaching process. METHODS: This was a
      methodological study with a quantitative and qualitative approach, which had the
      goal of instrumentation in reference to the construction and validation of
      measuring instruments. The instrument proposition design was based on the
      literature on leadership, coaching, and assessment of psychometric properties,
      subjected to content validation as to clarity, relevance, and applicability in
      order to validate the propositions through the consensus of judges, using the
      Delphi technique, in 2010. The final version of the questionnaires was
      administered to 279 nurses and 608 nurse technicians and licensed practical
      nurses, at two university hospitals and two private hospitals. RESULTS: The
      Cronbach's alpha value with all items of the self-perception instrument was very
      high (0.911). The team members' instrument of perception showed that for all
      determinants and for each dimension of the coaching process, Cronbach's overall
      alpha value (0.952) was considered quite high, pointing to a very strong
      consistency of the scale. Confirmatory analysis showed that the models were well
      adjusted. CONCLUSION: From the statistical validation we compared the possibility
      of reusing the questionnaires for other study samples, because there was evidence
      of reliability and applicability.

PMID- 24728250
TI  - Low-level laser irradiation induces in vitro proliferation of mesenchymal stem
      cells.
AB  - OBJECTIVE: To evaluate the effect of low-level laser irradiation on the
      proliferation and possible nuclear morphological changes of mouse mesenchymal
      stem cells. METHODS: Mesenchymal stem cells derived from bone marrow and adipose
      tissue were submitted to two applications (T0 and T48 hours) of low-level laser
      irradiation (660 nm; doses of 0.5 and 1.0 J/cm2). The trypan blue assay was used
      to evaluate cell viability, and growth curves were used to analyze proliferation
      at zero, 24, 48, and 72 hours. Nuclear alterations were evaluated by staining
      with DAPI (4'-6-diamidino-2-phenylindole) at 72 hours. RESULTS: Bone marrow
      derived mesenchymal stem cells responded to laser therapy in a dose-dependent
      manner. Higher cell growth was observed when the cells were irradiated with a
      dose of 1.0 J/cm2, especially after 24 hours (p<0.01). Adipose-derived
      mesenchymal stem cells responded better to a dose of 1.0 J/cm2, but higher cell
      proliferation was observed after 48 hours (p<0.05) and 72 hours (p<0.01). Neither
      nuclear alterations nor a significant change in cell viability was detected in
      the studied groups. CONCLUSION: Low-level laser irradiation stimulated the
      proliferation of mouse mesenchymal stem cells without causing nuclear
      alterations. The biostimulation of mesenchymal stem cells using laser therapy
      might be an important tool for regenerative therapy and tissue engineering.

PMID- 24728251
TI  - Effects of different intensities of physical exercise on insulin sensitivity and
      protein kinase B/Akt activity in skeletal muscle of obese mice.
AB  - OBJECTIVE: To investigate the effects of different intensities of acute exercise
      on insulin sensitivity and protein kinase B/Akt activity in skeletal muscle of
      obese mice. METHODS: Swiss mice were randomly divided into four groups, and fed
      either a standard diet (control group) or high fat diet (obese sedentary group
      and obese exercise group 1 and 2) for 12 weeks. Two different exercise protocols
      were used: swimming for 1 hour with or without an overload of 5% body weight. The
      insulin tolerance test was performed to estimate whole-body sensitivity. Western
      blot technique was used to determine protein levels of protein kinase B/Akt and
      phosphorylation by protein Kinase B/Akt in mice skeletal muscle. RESULTS: A
      single bout of exercise inhibited the high fat diet-induced insulin resistance.
      There was increase in phosphorylation by protein kinase B/Akt serine, improve in
      insulin signaling and reduce of fasting glucose in mice that swam for 1 hour
      without overload and mice that swan for 1 hour with overload of 5%. However, no
      significant differences were seen between exercised groups. CONCLUSION:
      Regardless of intensity, aerobic exercise was able to improve insulin sensitivity
      and phosphorylation by protein kinase B/Ak, and proved to be a good form of
      treatment and prevention of type 2 diabetes.

PMID- 24728252
TI  - Analysis of smoke cessation rate and profile of former smokers living in Belo
      Horizonte and Metropolitan Region.
AB  - OBJECTIVE: To estimate the smoking cessation rate and to identify possible
      associated factors. METHODS: Individuals from the Metropolitan Region of Belo
      Horizonte (MG) aged 15 years or more who responded to the smoking supplement of
      the National Household Sample Survey were selected (n=1,297). An estimate was
      made of the tobacco-use cessation rate relative to the 95% confidence interval.
      To verify factors associated with smoking cessation, Pearson's chi2 test or
      Student's t test were used. RESULTS: The general smoking cessation rate was 56.7%
      (95% confidence interval: 52.3-61.1), with 57.7% among men and 55.5% among women.
      The associated factors were higher age and income. Among the 19 individuals who
      had stopped smoking for less than 12 months, 52.6% had been seen by a physician
      or healthcare professional in the previous 12 months, and 60% of them were
      oriented to stop smoking, but only 1 (16.7%) had been oriented at a unit of the
      public national Unified Healthcare System. CONCLUSION: Despite high rates of
      smoking cessation, the methods made available by the Unified Healthcare System
      did not show good results. It is necessary to enhance the healthcare programs
      that aim to reduce the proportion of smokers in the population. Such measures can
      have a positive long-term influence in droping mortality and morbidity rates
      associated with smoking and the costs for healthcare services.

PMID- 24728253
TI  - Successful management of neonatal alloimmune thrombocytopenia in the second
      pregnancy: a case report.
AB  - Neonatal alloimmune thrombocytopenia is a serious disease, in which the mother
      produces antibodies against fetal platelet antigens inherited from the father; it
      is still an underdiagnosed disease. This disease is considered the platelet
      counterpart of the RhD hemolytic disease of the fetus and newborn, yet in
      neonatal alloimmune thrombocytopenia the first child is affected with fetal
      and/or neonatal thrombocytopenia. There is a significant risk of intracranial
      hemorrhage and severe neurological impairment, with a tendency for earlier and
      more severe thrombocytopenia in subsequent pregnancies. This article reports a
      case of neonatal alloimmune thrombocytopenia in the second pregnancy affected and
      discusses diagnosis, management and the clinical importance of this disease. 

PMID- 24728254
TI  - Normalization of lymphocyte count after high ablative dose of I-131 in a patient
      with chronic lymphoid leukemia and secondary papillary carcinoma of the thyroid.
      Case report.
AB  - The authors report the case of a 70-year-old male patient with chronic lymphoid
      leukemia who presented subsequently a papillary carcinoma of the thyroid with
      metastases to regional lymph nodes. The patient was treated with surgical
      thyroidectomy with regional and cervical lymph node excision and radioiodine
      therapy (I-131). The protocolar control scintigraphy 4 days after the radioactive
      dose showed I-131 uptake in both axillae and even in the inguinal regions. PET/CT
      showed faint FDG-F-18 uptake in one lymph node of the left axilla. An ultrasound
      guided fine needle biopsy of this lymph node identified by I-131 SPECT/CT and FDG
      F-18 PET/CT revealed lymphoma cells and was negative for thyroid tissue and
      thyroglobulin content. The sequential blood counts done routinely after radiation
      treatment showed a marked fall until return to normal values of leucocytes and
      lymphocytes (absolute and relative), which were still normal in the last control
      19 months after the radioiodine administration. Chest computed tomography showed
      a decrease in size of axillary and para-aortic lymph nodes. By
      immunohistochemistry, cells of the lymphoid B lineage decreased from 52% before
      radioiodine therapy to 5% after the procedure. The authors speculate about a
      possible sodium iodide symporter expression by the cells of this lymphoma,
      similar to some other non-thyroid tumors, such as breast cancer cells. 

PMID- 24728255
TI  - Submacular hemorrhage secondary to congenital toxoplasmosis.
AB  - We report the case of a patient with congenital toxoplasmosis and submacular
      hemorrhage caused by a neovascular membrane who underwent an intravitreal
      injection of C3F8 and bevacizumab, and had a good visual recovery. 

PMID- 24728256
TI  - Recurrence of acute myeloid leukemia in cryptorchid testis: case report.
AB  - A 23-year-old male with a history of bone marrow transplant for acute myeloid
      leukemia. He presented a large mass in the right inguinal region 5 years ago.
      Upon physical examination, right-sided cryptorchidism was observed. The tumor
      markers alpha-fetoprotein and beta-HCG were within normalcy range and lactate
      dehydrogenase was raised. Computed tomography of the abdomen and pelvis revealed
      right testicular mass in contiguity with the inguinal canal to the ipsilateral
      retroperitoneum, associated with right hydronephrosis. Due to the risk of germ
      cell tumor in undescended testicle, the patient underwent radical right
      orchiectomy. The pathological examination showed recurrence of acute myeloid
      leukemia in the testis. He was referred to oncology for adjuvant therapy. Our
      literature review found no similar cases described. 

PMID- 24728257
TI  - Antiretroviral drugs and acute pancreatitis in HIV/AIDS patients: is there any
      association? A literature review.
AB  - In HIV-seropositive individuals, the incidence of acute pancreatitis may achieve
      40% per year, higher than the 2% found in the general population. Since 1996,
      when combined antiretroviral therapy, known as HAART (highly active
      antiretroviral therapy), was introduced, a broad spectrum of harmful factors to
      the pancreas, such as opportunistic infections and drugs used for
      chemoprophylaxis, dropped considerably. Nucleotide analogues and metabolic
      abnormalities, hepatic steatosis and lactic acidosis have emerged as new
      conditions that can affect the pancreas. To evaluate the role of antiretroviral
      drugs to treat HIV/AIDS in a scenario of high incidence of acute pancreatitis in
      this population, a systematic review was performed, including original articles,
      case reports and case series studies, whose targets were HIV-seropositive
      patients that developed acute pancreatitis after exposure to any antiretroviral
      drugs. This association was confirmed after exclusion of other possible
      etiologies and/or a recurrent episode of acute pancreatitis after re-exposure to
      the suspected drug. Zidovudine, efavirenz, and protease inhibitors are thought to
      lead to acute pancreatitis secondary to hyperlipidemia. Nucleotide reverse
      transcriptase inhibitors, despite being powerful inhibitors of viral replication,
      induce a wide spectrum of side effects, including myelotoxicity and acute
      pancreatitis. Didanosine, zalcitabine and stavudine have been reported as causes
      of acute and chronic pancreatitis. They pose a high risk with cumulative doses.
      Didanosine with hydroxyurea, alcohol or pentamidine are additional risk factors,
      leading to lethal pancreatitis, which is not a frequent event. In addition, other
      drugs used for prophylaxis of AIDS-related opportunistic diseases, such as
      sulfamethoxazole-trimethoprim and pentamidine, can produce necrotizing
      pancreatitis. Despite comorbidities that can lead to pancreatic involvement in
      the HIV/AIDS population, antiretroviral drug-induced pancreatitis should always
      be considered in the diagnosis of patients with abdominal pain and elevated
      pancreatic enzymes. 

PMID- 24728258
TI  - Obesity and lung function: a systematic review.
AB  - Obesity is a chronic disease characterized by the excessive accumulation of body
      fat that is harmful to the individuals. Respiratory disorders are among the
      comorbidities associated with obesity. This study had the objective of
      investigating the alterations in respiratory function that affect obese
      individuals. A systematic review was performed, by selecting publications in the
      science databases MEDLINE and LILACS, using PubMed and SciELO. The articles that
      assessed pulmonary function by plethysmography and/or spirometry in obese
      individuals aged under 18 years were included. The results demonstrated that the
      obese individuals presented with a reduction in lung volume and capacity as
      compared to healthy individuals. Reduction of total lung capacity and reduction
      of forced vital capacity, accompanied by reduction of the forced expiratory
      volume after one second were the most representative findings in the samples. The
      articles analyzed proved the presence of a restrictive respiratory pattern
      associated with obesity. 

PMID- 24728259
TI  - Role of the phosphocreatine system on energetic homeostasis in skeletal and
      cardiac muscles.
AB  - Adenosine triphosphate is the present energy currency in the body, and is used in
      various cellular and indispensable processes for the maintenance of cell
      homeostasis. The regeneration mechanisms of adenosine triphosphate, from the
      product of its hydrolysis - adenosine diphosphate - are therefore necessary.
      Phosphocreatine is known as its quickest form of regeneration, by means of the
      enzyme creatine kinase. Thus, the primary function of this system is to act as a
      temporal energy buffer. Nevertheless, over the years, several other functions
      were attributed to phosphocreatine. This occurs as various isoforms of creatine
      kinase isoforms have been identified with a distinct subcellular location and
      functionally coupled with the sites that generate and use energy, in the
      mitochondria and cytosol, respectively. The present study discussed the central
      and complex role that the phosphocreatine system performs in energy homeostasis
      in muscle cells, as well as its alterations in pathological conditions. 

PMID- 24728260
TI  - Of periauricular pits and sinuses: understanding the masqueraders.

PMID- 24728261
TI  - Cardiac stem cells and their clinical use.
AB  - Stem cells have been used to correct the ravages of atherosclerotic heart disease
      and other diseases that involve acute deficit of myocardial muscle, such as
      myocarditis. Previous attempts at using bone marrow derived from stem cells have
      not been particularly successful. New technologies using cardiac stem cells seem
      to offer a better perspective of obtaining such regeneration. 

PMID- 24728262
TI  - Serial echocardiographic assessment of evolution of ductus arteriosus in preterm
      infants.

PMID- 24728263
TI  - What changes in research ethics in Brazil: resolution no. 466/12 of the National
      Health Council.

PMID- 24728264
TI  - Towards the elucidation of the high oxygen electroreduction activity of PtxY:
      surface science and electrochemical studies of Y/Pt(111).
AB  - We have prepared an yttrium modified Pt(111) single crystal under ultra-high
      vacuum conditions, simulating a bulk alloy. A Pt overlayer is formed upon
      annealing the crystal above 800 K. The annealed structure binds CO weaker than
      Pt(111), with a pronounced peak at 295 K in the temperature programmed desorption
      of CO. When depositing a large amount of yttrium at 1173 K, a (1.88 * 1.88)R30
      degrees  structure relative to Pt(111) was observed by low energy electron
      diffraction. Such an electron diffraction pattern could correspond to a (2 *
      2)R30 degrees  structure under 6% compressive strain. This structure is in
      agreement with the structure of the vacancies in a Pt Kagome layer in Pt5Y
      rotated 30 degrees  with respect to the bulk of the Pt(111). The Pt overlayer is
      relatively stable in air; however, after performing oxygen reduction activity
      measurements in an electrochemical cell, a thick Pt overlayer was measured by the
      angle resolved X-ray photoelectron spectroscopy depth profile. The activity of
      the annealed Y/Pt(111) for the oxygen reduction reaction was similar to that of
      polycrystalline Pt3Y. 

PMID- 24728265
TI  - Urinary bladder mucosal responses to ischemia.
AB  - PURPOSE: The objectives of this study were to examine the expression of various
      cellular proteins within the urothelium (UT) and lamina propria (LP) following
      chronic bladder ischemia in the rat urinary bladder. MATERIALS AND METHODS:
      Urinary bladders were removed from adult Sprague-Dawley rats 8 weeks after
      creation of bladder ischemia and from sham controls. Immunocytochemistry was used
      to examine distribution of LP-vimentin-immunoreactive (IR) cells and connexins
      (Cx26; Cx43), and western immunoblotting or ELISA for proteins involved in UT
      barrier and sensory functions. RESULTS: Ischemia was associated with a
      significant increase in LP-vimentin-IR cells and increased expression of the gap
      junction proteins Cx26 and Cx43 within the bladder UT as compared to sham
      control. Ischemia also resulted in an increased (p < 0.05) expression level of
      the junctional marker (ZO-1) and non-significantly increased expressions of the
      trophic factor nerve growth factor as well as norepinephrine. CONCLUSIONS: Our
      findings reveal that chronic ischemia alters a number of proteins within the UT
      and underlying LP. These proteins are involved in barrier function, remodeling,
      repair as well as intercellular communication. The increased expression of LP
      vimentin-IR cells suggests that changes in cell-cell interactions could play a
      role in ischemia-induced changes in bladder activity.

PMID- 24728266
TI  - Comparison of metal on metal versus polyethylene-ceramic bearing in uncemented
      total hip arthroplasty in patients with haemophilic arthropathy.
AB  - PURPOSE: We report the results of a consecutive series of 12 cases with
      haemophilic hip arthropathy treated with uncemented total hip arthroplasty (THA).
      Our hypothesis was that THA results in the haemophilic group would be inferior to
      those in the nonhaemophilic group. METHODS: The clinical histories of 12
      consecutive THAs in eight patients (all men) with hereditary bleeding disorders
      (haemophilia A and B and von Willebrand disease) were reviewed retrospectively.
      The results were compared with an age- and sex-matched control group without
      haemophilia, with special emphasis on bearing surfaces (Metasul metal-on-metal;
      polyethylene-ceramic articulation). RESULTS: The mean follow-up of the control
      group was 9.7 (range five to 24) years and was similar to the haemophilia group,
      with 10.4. Survival in the Metasul haemophilic group was 22.2 % after 18 years,
      which significantly differed from the Metasul control group (100 % after 24
      years). Survival of the polyethylene-ceramic haemophilic group was similar to the
      control group (100 % after seven years in both groups). CONCLUSIONS: The metal-on
      metal bearing surface in patients with haemophilia gave inferior results compared
      with nonhaemophilic patients. The use of metal-on-metal bearings in haemophilia
      is debatable.

PMID- 24728267
TI  - Implication of sperm RNAs in transgenerational inheritance of the effects of
      early trauma in mice.
AB  - Small non-coding RNAs (sncRNAs) are potential vectors at the interface between
      genes and environment. We found that traumatic stress in early life altered mouse
      microRNA (miRNA) expression, and behavioral and metabolic responses in the
      progeny. Injection of sperm RNAs from traumatized males into fertilized wild-type
      oocytes reproduced the behavioral and metabolic alterations in the resulting
      offspring. 

PMID- 24728268
TI  - Volitional modulation of optically recorded calcium signals during
      neuroprosthetic learning.
AB  - Brain-machine interfaces are not only promising for neurological applications,
      but also powerful for investigating neuronal ensemble dynamics during learning.
      We trained mice to operantly control an auditory cursor using spike-related
      calcium signals recorded with two-photon imaging in motor and somatosensory
      cortex. Mice rapidly learned to modulate activity in layer 2/3 neurons, evident
      both across and within sessions. Learning was accompanied by modifications of
      firing correlations in spatially localized networks at fine scales. 

PMID- 24728269
TI  - Single App knock-in mouse models of Alzheimer's disease.
AB  - Experimental studies of Alzheimer's disease have largely depended on transgenic
      mice overexpressing amyloid precursor protein (APP). These mice, however, suffer
      from artificial phenotypes because, in addition to amyloid beta peptide (Abeta),
      they overproduce other APP fragments. We generated knock-in mice that harbor
      Swedish and Beyreuther/Iberian mutations with and without the Arctic mutation in
      the APP gene. The mice showed typical Abeta pathology, neuroinflammation and
      memory impairment in an age-dependent manner. 

PMID- 24728270
TI  - An individual patient-based meta-analysis of the effects of dronedarone in
      patients with atrial fibrillation.
AB  - AIMS: Dronedarone is a non-iodinated benzofuran derivative with antiarrhythmic
      properties. In placebo-controlled atrial fibrillation (AF) trials, the drug was
      found to have divergent effects on endpoints such as cardiovascular death or
      hospitalization. The objective of this meta-analysis of all placebo-controlled
      studies was to provide insights on possible reasons for these divergent effects.
      METHODS AND RESULTS: Individual data on 9664 patients were used from all AF
      placebo-controlled studies. The primary outcome measure was cardiovascular death.
      Cardiovascular hospitalization and hospitalization for heart failure were
      secondary endpoints. Predefined procedures were used to reduce inter-study
      heterogeneity adjusting for important baseline variables using a Cox model.
      Despite adjustments, a significant inter-trial heterogeneity of the outcome of
      cardiovascular mortality persisted (P-value of 0.005 for the treatment effect *
      study interaction). Further analyses were conducted in subgroups based on
      baseline clinical criteria: digoxin co-prescription, advanced heart failure,
      coronary artery disease, or the presence of permanent AF. These analyses allowed
      the calculation of a global treatment effect in two important patient subgroups,
      those with permanent AF in whom there was harm with respect to cardiovascular
      mortality [hazard ratio (HR) = 2.32; 95% confidence interval (CI) 1.13-4.75] and
      hospitalization for heart failure (HR = 1.674; 95% CI 1.05-2.67); and those with
      non-permanent AF in whom there was benefit in terms of cardiovascular
      hospitalization [HR = 0.751 95% CI (0.68-0.83)]. CONCLUSION: This meta-analysis
      demonstrates significant heterogeneity of dronedarone treatment effects across
      the placebo-controlled randomized trials. The most important predictor of a
      harmful effect of dronedarone on cardiovascular death and heart failure
      hospitalization was the presence of permanent AF.

PMID- 24728272
TI  - A Burkholderia cenocepacia gene encoding a non-functional tyrosine phosphatase is
      required for the delayed maturation of the bacteria-containing vacuoles in
      macrophages.
AB  - Burkholderia cenocepacia infects patients with cystic fibrosis. We have
      previously shown that B. cenocepacia can survive in macrophages within membrane
      vacuoles [B. cenocepacia-containing vacuoles (BcCVs)] that preclude fusion with
      the lysosome. The bacterial factors involved in B. cenocepacia intracellular
      survival are not fully elucidated. We report here that deletion of BCAM0628,
      encoding a predicted low molecular weight protein tyrosine phosphatase (LMW-PTP)
      that is restricted to B. cenocepacia strains of the transmissible ET-12 clone,
      accelerates the maturation of the BcCVs. Compared to the parental strain and
      deletion mutants in other LMW-PTPs that are widely conserved in Burkholderia
      species, a greater proportion of BcCVs containing the DeltaBCAM0628 mutant were
      targeted to the lysosome. Accelerated BcCV maturation was not due to reduced
      intracellular viability since DeltaBCAM0628 survived and replicated in
      macrophages similarly to the parental strain. Therefore, BCAM0628 was referred to
      as dpm (delayed phagosome maturation). We provide evidence that the Dpm protein
      is secreted during growth in vitro and upon macrophage infection. Dpm secretion
      requires an N-terminal signal peptide. Heterologous expression of Dpm in
      Burkholderia multivorans confers to this bacterium a similar phagosomal
      maturation delay to that found with B. cenocepacia. We demonstrate that Dpm is an
      inactive phosphatase, suggesting that its contribution to phagosomal maturation
      arrest must be unrelated to tyrosine phosphatase activity. 

PMID- 24728271
TI  - Inactivation of the antibacterial and cytotoxic properties of silver ions by
      biologically relevant compounds.
AB  - There has been a recent surge in the use of silver as an antimicrobial agent in a
      wide range of domestic and clinical products, intended to prevent or treat
      bacterial infections and reduce bacterial colonization of surfaces. It has been
      reported that the antibacterial and cytotoxic properties of silver are affected
      by the assay conditions, particularly the type of growth media used in vitro. The
      toxicity of Ag+ to bacterial cells is comparable to that of human cells. We
      demonstrate that biologically relevant compounds such as glutathione, cysteine
      and human blood components significantly reduce the toxicity of silver ions to
      clinically relevant pathogenic bacteria and primary human dermal fibroblasts
      (skin cells). Bacteria are able to grow normally in the presence of silver
      nitrate at >20-fold the minimum inhibitory concentration (MIC) if Ag+ and thiols
      are added in a 1:1 ratio because the reaction of Ag+ with extracellular thiols
      prevents silver ions from interacting with cells. Extracellular thiols and human
      serum also significantly reduce the antimicrobial activity of silver wound
      dressings Aquacel-Ag (Convatec) and Acticoat (Smith & Nephew) to Staphylococcus
      aureus, Pseudomonas aeruginosa and Escherichia coli in vitro. These results have
      important implications for the deployment of silver as an antimicrobial agent in
      environments exposed to biological tissue or secretions. Significant amounts of
      money and effort have been directed at the development of silver-coated medical
      devices (e.g. dressings, catheters, implants). We believe our findings are
      essential for the effective design and testing of antimicrobial silver coatings.

PMID- 24728274
TI  - Neocarzinostatin-based hybrid biocatalysts for oxidation reactions.
AB  - An anionic iron(III)-porphyrin-testosterone conjugate 1-Fe has been synthesized
      and fully characterized. It has been further associated with a neocarzinostatin
      variant, NCS-3.24, to generate a new artificial metalloenzyme following the so
      called 'Trojan Horse' strategy. This new 1-Fe-NCS-3.24 biocatalyst showed an
      interesting catalytic activity as it was found able to catalyze the
      chemoselective and slightly enantioselective (ee = 13%) sulfoxidation of
      thioanisole by H2O2. Molecular modelling studies show that a synergy between the
      binding of the steroid moiety and that of the porphyrin macrocycle into the
      protein binding site can explain the experimental results, indicating a better
      affinity of 1-Fe for the NCS-3.24 variant than testosterone and testosterone
      hemisuccinate themselves. They also show that the Fe-porphyrin complex is
      sandwiched between the two subdomains of the protein providing with good
      complementarities. However, the artificial cofactor entirely fills the cavity and
      its metal ion remains widely exposed to the solvent which explains the moderate
      enantioselectivity observed. Some possible improvements in the "Trojan Horse"
      strategy for obtaining better catalysts of selective oxidations are presented.

PMID- 24728273
TI  - ERGO: a pilot study of ketogenic diet in recurrent glioblastoma.
AB  - Limiting dietary carbohydrates inhibits glioma growth in preclinical models.
      Therefore, the ERGO trial (NCT00575146) examined feasibility of a ketogenic diet
      in 20 patients with recurrent glioblastoma. Patients were put on a low
      carbohydrate, ketogenic diet containing plant oils. Feasibility was the primary
      endpoint, secondary endpoints included the percentage of patients reaching
      urinary ketosis, progression-free survival (PFS) and overall survival. The
      effects of a ketogenic diet alone or in combination with bevacizumab was also
      explored in an orthotopic U87MG glioblastoma model in nude mice. Three patients
      (15%) discontinued the diet for poor tolerability. No serious adverse events
      attributed to the diet were observed. Urine ketosis was achieved at least once in
      12 of 13 (92%) evaluable patients. One patient achieved a minor response and two
      patients had stable disease after 6 weeks. Median PFS of all patients was 5
      (range, 3-13) weeks, median survival from enrollment was 32 weeks. The trial
      allowed to continue the diet beyond progression. Six of 7 (86%) patients treated
      with bevacizumab and diet experienced an objective response, and median PFS on
      bevacizumab was 20.1 (range, 12-124) weeks, for a PFS at 6 months of 43%. In the
      mouse glioma model, ketogenic diet alone had no effect on median survival, but
      increased that of bevacizumab-treated mice from 52 to 58 days (p<0.05). In
      conclusion, a ketogenic diet is feasible and safe but probably has no significant
      clinical activity when used as single agent in recurrent glioma. Further clinical
      trials are necessary to clarify whether calorie restriction or the combination
      with other therapeutic modalities, such as radiotherapy or anti-angiogenic
      treatments, could enhance the efficacy of the ketogenic diet. 

PMID- 24728275
TI  - Repetitive and retinotopically restricted activation of the dorsal lateral
      geniculate nucleus with optogenetics.
AB  - Optogenetics allows the control of cellular activity using focused delivery of
      light pulses. In neuroscience, optogenetic protocols have been shown to
      efficiently inhibit or stimulate neuronal activity with a high temporal
      resolution. Among the technical challenges associated with the use of
      optogenetics, one is the ability to target a spatially specific population of
      neurons in a given brain structure. To address this issue, we developed a side
      illuminating optical fiber capable of delivering light to specific sites in a
      target nucleus with added flexibility through rotation and translation of the
      fiber and by varying the output light power. The designed optical fiber was
      tested in vivo in visual structures of ChR2-expressing transgenic mice. To assess
      the spatial extent of neuronal activity modulation, we took advantage of the
      hallmark of the visual system: its retinotopic organization. Indeed, the relative
      position of ganglion cells in the retina is transposed in the cellular topography
      of both the dorsal lateral geniculate nucleus (LGN) in the thalamus and the
      primary visual cortex (V1). The optical fiber was inserted in the LGN and by
      rotating it with a motor, it was possible to sequentially activate different
      neuronal populations within this structure. The activation of V1 neurons by LGN
      projections was recorded using intrinsic optical imaging. Increasing light
      intensity (from 1.4 to 8.9 mW/mm2) led to increasing activation surfaces in V1.
      Optogenetic stimulation of the LGN at different translational and rotational
      positions was associated with different activation maps in V1. The position
      and/or orientation of the fiber inevitably varied across experiments, thus
      limiting the capacity to pool data. With the optogenetic design presented here,
      we demonstrate for the first time a transitory and spatially-concise activation
      of a deep neuronal structure. The optogenetic design presented here thus opens a
      promising avenue for studying the function of deep brain structures.

PMID- 24728276
TI  - Mercury in indigenous, introduced and farmed fish from the semiarid region of the
      Jaguaribe river Basin, NE Brazil.
AB  - Indigenous, introduced and farmed fish species were collected from the Jaguaribe
      Basin, NE Brazil to assess total and methyl mercury concentrations in muscle
      tissue and to determine its relationship with fish origin. The results obtained
      from introduced species were compared to the Hg content of their original area of
      occurrence, which is located in the Amazon region. Farmed and wild individuals of
      Oreochromis niloticus (tilapia) were also compared. Introduced species presented
      lower Hg contents compared to their Amazonian counterparts. Wild individuals of
      O. niloticus also presented higher Hg contents than farmed individuals with
      similar sizes. However, methyl Hg concentrations were not significantly different
      between the two groups. Total Hg and methyl Hg concentrations were higher in
      carnivorous species, especially those from the Amazon region, and surpassed the
      Brazilian guidelines for fish consumption. Based on their Hg content, Jaguaribe
      basin fish do not pose a significant threat to human consumption. 

PMID- 24728277
TI  - Repair of segmental bone defect using Totally Vitalized tissue engineered bone
      graft by a combined perfusion seeding and culture system.
AB  - BACKGROUND: The basic strategy to construct tissue engineered bone graft (TEBG)
      is to combine osteoblastic cells with three dimensional (3D) scaffold. Based on
      this strategy, we proposed the "Totally Vitalized TEBG" (TV-TEBG) which was
      characterized by abundant and homogenously distributed cells with enhanced cell
      proliferation and differentiation and further investigated its biological
      performance in repairing segmental bone defect. METHODS: In this study, we
      constructed the TV-TEBG with the combination of customized flow perfusion
      seeding/culture system and beta-tricalcium phosphate (beta-TCP) scaffold
      fabricated by Rapid Prototyping (RP) technique. We systemically compared three
      kinds of TEBG constructed by perfusion seeding and perfusion culture (PSPC)
      method, static seeding and perfusion culture (SSPC) method, and static seeding
      and static culture (SSSC) method for their in vitro performance and bone defect
      healing efficacy with a rabbit model. RESULTS: Our study has demonstrated that
      TEBG constructed by PSPC method exhibited better biological properties with
      higher daily D-glucose consumption, increased cell proliferation and
      differentiation, and better cell distribution, indicating the successful
      construction of TV-TEBG. After implanted into rabbit radius defects for 12 weeks,
      PSPC group exerted higher X-ray score close to autograft, much greater mechanical
      property evidenced by the biomechanical testing and significantly higher new bone
      formation as shown by histological analysis compared with the other two groups,
      and eventually obtained favorable healing efficacy of the segmental bone defect
      that was the closest to autograft transplantation. CONCLUSION: This study
      demonstrated the feasibility of TV-TEBG construction with combination of
      perfusion seeding, perfusion culture and RP technique which exerted excellent
      biological properties. The application of TV-TEBG may become a preferred
      candidate for segmental bone defect repair in orthopedic and maxillofacial
      fields.

PMID- 24728278
TI  - Novel antibody against a glutamic acid-rich human fibrinogen-like protein 2
      derived peptide near Ser91 inhibits hfgl2 prothrombinase activity.
AB  - Fibrinogen-like protein 2 (fgl2) is highly expressed in microvascular endothelial
      cells in diseases associated with microcirculatory disturbances and plays a
      crucial role in microthrombosis. Previous studies have demonstrated that the
      Ser89 residue is a critical site for mouse fgl2 prothrombinase activity. The aim
      of this study was to investigate the prothrombinase inhibitory ability of
      antibodies against an hfgl2-derived peptide. The peptide was termed NPG-12
      because it is located at the N-terminus of membrane-bound hfgl2, contains 12
      amino acid residues (corresponding to residues 76 to 87), and is rich in Glu.
      This peptide was selected as an antigenic determinant to produce antibodies in
      immunized rabbits using the DNAStar and HomoloGene software program. Abundant
      hfgl2 expression was induced in human umbilical vein endothelial cells through
      treatment with TNF-alpha. The generated anti-NPG-12 antibodies specifically
      recognize fgl2, as determined by ELISA, Western Blot and immunostaining.
      Moreover, one-stage clotting and thrombin generation tests provide evidence that
      the antibodies can reduce the hfgl2 prothrombinase activity without affecting the
      platelet-poor plasma prothrombin time (PT) or the activated partial
      thromboplastin time (APTT). In addition, the antibodies exerted undetectable
      influence on the proliferation or activation of bulk T cell populations. In
      conclusion, the selected peptide sequence NPG-12 may be a critical domain for
      hfgl2 prothrombinase activity, and the development of inhibitors against this
      sequence may be promising for research or management of hfgl2-associated
      microcirculatory disturbances. 

PMID- 24728279
TI  - Modified thyroplasty for unilateral vocal fold paralysis using an adjustable
      titanium implant.
AB  - This study aimed to describe a new titanium thyroplasty implant that can be
      adjusted with a screw. Six Beagle dogs were randomly divided into experimental
      and control groups (n = 3). The titanium screw was implanted in the experimental
      group after the left recurrent laryngeal nerve was cut off under general
      anaesthesia. This procedure caused arytenoid cartilage internal shift, allowing
      the vocal cord to locate at the median and the glottis to close during phonation.
      No other operation was conducted in the control group. Each group, respectively,
      underwent video laryngoscopy, CT scan and histopathology before and after
      operation. After 4 months of follow-up, the video laryngoscopy results showed
      that the left arytenoid cartilage in the experimental group underwent internal
      adduct and shift, whereas the left vocal cords in the control group located at
      the paramedian position and exhibited fissure during phonation. CT scan results
      showed that the adjustable titanium screw was in proper position. Postoperative
      pathological examination showed that, in addition to early local inflammation,
      the laryngeal muscle may atrophy. The adjustable titanium screw requires a simple
      operation and can be significantly adjusted. The effect of the operation can be
      immediately observed without rejection. Therefore, this method is an efficient
      treatment for unilateral vocal cord paralysis.

PMID- 24728284
TI  - Accurate hierarchical control of hollow crossed NiCo2O4 nanocubes for superior
      lithium storage.
AB  - An effective approach of simultaneously coordinating etching and precipitation
      reactions is employed to prepare hollow crossed NiCo2O4 nanocubes as anode
      materials for lithium-ion batteries. Firstly, amorphous hollow (NiCox)O(OH)
      nanoboxes form uniformly, and subsequent calcination results in the formation of
      NiCo2O4 nanocubes that exhibit a stable reversible capacity of 1160 mA h g(-1) at
      constant current density of 200 mA g(-1) with capacity retention of over 91.1%
      after 200 cycles. The unique hollow structure can shorten the Li-ion diffusion
      path, which benefits the rate of performance. Furthermore, the hollow structure
      offers a sufficient void space to alleviate the mechanical stress caused by
      volume change. Additionally, the multi-element characteristics of active
      materials allow the volume change to take place in a stepwise manner. Therefore,
      hollow crossed NiCo2O4 nanocube electrodes exhibit excellent electrochemical
      performance. This method is simple and of low cost, which may open a new avenue
      for fast synthesis of hollow crossed structural nano-functional materials for
      energy storage, catalysts, sensors and other new applications. 

PMID- 24728285
TI  - Auditory cortex activation is modulated by somatosensation in a case of tactile
      tinnitus.

PMID- 24728280
TI  - Dissecting a hidden gene duplication: the Arabidopsis thaliana SEC10 locus.
AB  - Repetitive sequences present a challenge for genome sequence assembly, and highly
      similar segmental duplications may disappear from assembled genome sequences.
      Having found a surprising lack of observable phenotypic deviations and non
      Mendelian segregation in Arabidopsis thaliana mutants in SEC10, a gene encoding a
      core subunit of the exocyst tethering complex, we examined whether this could be
      explained by a hidden gene duplication. Re-sequencing and manual assembly of the
      Arabidopsis thaliana SEC10 (At5g12370) locus revealed that this locus, comprising
      a single gene in the reference genome assembly, indeed contains two paralogous
      genes in tandem, SEC10a and SEC10b, and that a sequence segment of 7 kb in length
      is missing from the reference genome sequence. Differences between the two
      paralogs are concentrated in non-coding regions, while the predicted protein
      sequences exhibit 99% identity, differing only by substitution of five amino acid
      residues and an indel of four residues. Both SEC10 genes are expressed, although
      varying transcript levels suggest differential regulation. Homozygous T-DNA
      insertion mutants in either paralog exhibit a wild-type phenotype, consistent
      with proposed extensive functional redundancy of the two genes. By these
      observations we demonstrate that recently duplicated genes may remain hidden even
      in well-characterized genomes, such as that of A. thaliana. Moreover, we show
      that the use of the existing A. thaliana reference genome sequence as a guide for
      sequence assembly of new Arabidopsis accessions or related species has at least
      in some cases led to error propagation. 

PMID- 24728286
TI  - Lumbosacral transitional vertebra and S1 radiculopathy: the value of coronal MR
      imaging.
AB  - INTRODUCTION: The association of a lumbosacral transitional vertebra with
      accelerated degeneration of the disc above has been described. Lumbosacral
      transitional vertebrae have also been reported as a cause of extraforaminal
      entrapment of the L5 nerve root between the transverse segment of the
      transitional vertebra and the sacral ala optimally demonstrated by coronal MRI.
      The association of the lumbosacral transitional vertebra pseudoarthroses and S1
      nerve root entrapment due to degenerative stenosis of the nerve root canal has
      never been described. METHODS: We present 12 patients with lumbosacral
      transitional vertebrae that were referred for symptoms and signs of S1 nerve root
      radiculopathy in which the sagittal and axial MRI sequences failed to identify a
      plausible cause for the patients' S1 nerve root symptoms. A coronal T1-weighted
      imaging (T1WI) MRI sequence was consequently added to the investigation. RESULTS:
      The coronal T1WI MRI sequence demonstrated hypertrophic degenerative stenosis of
      the S1 nerve root canal at the level of the lumbosacral transitional vertebra
      pseudoarthrosis, with entrapment of the respective S1 nerve root in all patients.
      CONCLUSION: We emphasize the value of coronal T1WI MRI of the lumbosacral
      junction and sacrum if the cause for S1 radicular symptoms was not identified on
      conventional sagittal and axial MRI sequences in patients with lumbosacral
      transitional vertebrae.

PMID- 24728287
TI  - [Astigmatism after keratoplasty: influence of orthotopic transplantation].
AB  - BACKGROUND: Patients undergoing corneal transplantation often suffer from
      postoperative reduced vision due to high astigmatism. This retrospective study
      analyzed the influence of heterotopic or orthotopic transplantation on
      astigmatism and visual outcome. PATIENTS AND METHODS: In this study 373 eyes of
      334 patients were analyzed. Group 1 (OT) contained 186 eyes, which underwent
      orthotopic transplantation (side of recipient and donor corresponded), whereas
      group 2 (HT) included 187 heterotopic keratoplasties (donor cornea placed in the
      recipient's contralateral side). After 1, 3, 6, 12 and 24 months the median of
      keratometric astigmatism, objective astigmatism, topographic astigmatism and best
      corrected visual acuity (BCVA) were assessed and compared between groups.
      RESULTS: The long-term results showed no statistically significant differences
      regarding keratometric and objective astigmatism, whereas topographic astigmatism
      differed significantly (p = 0.04) after 3 months. We observed a lower astigmatism
      of 5.7 dpt (range 3.08-7.78 dpt) in group OT than in the group HT with 7.1 dpt
      (range 3.9-10.7 dpt). No differences were found at the other time points. The
      BCVA showed a significantly better effect after 1 month (p = 0.01) in the OT
      group of 0.2 (0.1-0.3) than in HT group of 0.1 (0.05/0.25). In the postoperative
      course no additional significant dissimilarities were documented. CONCLUSIONS:
      Heterotopic and orthotopic keratoplasty show no significant long-term differences
      in astigmatism and visual outcom.

PMID- 24728288
TI  - Impairments in goal-directed actions predict treatment response to cognitive
      behavioral therapy in social anxiety disorder.
AB  - Social anxiety disorder is characterized by excessive fear and habitual avoidance
      of social situations. Decision-making models suggest that patients with anxiety
      disorders may fail to exhibit goal-directed control over actions. We therefore
      investigated whether such biases may also be associated with social anxiety and
      to examine the relationship between such behavior with outcomes from cognitive
      behavioral therapy. Patients diagnosed with social anxiety and controls completed
      an instrumental learning task in which two actions were performed to earn food
      outcomes. After outcome devaluation, where one outcome was consumed to satiety,
      participants were re-tested in extinction. Results indicated that, as expected,
      controls were goal-directed, selectively reducing responding on the action that
      previously delivered the devalued outcome. Patients with social anxiety, however,
      exhibited no difference in responding on either action. This loss of a
      devaluation effect was associated with greater symptom severity and poorer
      response to therapy. These findings indicate that variations in goal-directed
      control in social anxiety may represent both a behavioral endophenotype and may
      be used to predict individuals who will respond to learning-based therapies. 

PMID- 24728289
TI  - In situ catalytic growth of large-area multilayered graphene/MoS2
      heterostructures.
AB  - Stacking various two-dimensional atomic crystals on top of each other is a
      feasible approach to create unique multilayered heterostructures with desired
      properties. Herein for the first time, we present a controlled preparation of
      large-area graphene/MoS2 heterostructures via a simple heating procedure on Mo
      oleate complex coated sodium sulfate under N2 atmosphere. Through a direct in
      situ catalytic reaction, graphene layer has been uniformly grown on the MoS2 film
      formed by the reaction of Mo species with Species, which is from the carbothermal
      reduction of sodium sulfate. Due to the excellent graphene "painting" on MoS2
      atomic layers, the significantly shortened lithium ion diffusion distance and the
      markedly enhanced electronic conductivity, these multilayered graphene/MoS2
      heterostructures exhibit high specific capacity, unprecedented rate performance
      and outstanding cycling stability, especially at a high current density, when
      used as an anode material for lithium batteries. This work provides a simple but
      efficient route for the controlled fabrication of large-area multilayered
      graphene/metal sulfide heterostructures with promising applications in battery
      manufacture, electronics or catalysis.

PMID- 24728290
TI  - Silver nanoparticle aided self-healing of polyelectrolyte multilayers.
AB  - Self-healing is the ability of a material to repair mechanical damage. The
      lifetime of a coating or film might be lengthened with this capacity. Water
      enabled self-healing of polyelectrolyte multilayers has been reported, using
      systems that grow via the interdiffusion of polyelectrolyte chains. Due to high
      mobility of the polyelectrolyte chains within the assembly, it is possible for
      lateral diffusion to heal over scratches. The influence of metal ions and
      nanoparticles on this property has, however, not been previously studied. Here we
      demonstrate that the incorporation of silver nanoparticles reduced in situ within
      the branched poly(ethyleneimine)-poly(acrylic acid) polyelectrolyte multilayer
      structure speeds the ability of the multilayer assembly to self-heal. This
      enhancement of property seems to not be due to changes in mechanical properties
      but rather in enhanced affinity to water and plasticization that enables the film
      to better swell. 

PMID- 24728291
TI  - Thyroid function and body weight: a community-based longitudinal study.
AB  - OBJECTIVE: Body weight and overt thyroid dysfunction are associated. Cross
      sectional population-based studies have repeatedly found that thyroid hormone
      levels, even within the normal reference range, might be associated with body
      weight. However, for longitudinal data, the association is less clear. Thus, we
      tested the association between serum thyrotropin (TSH) and body weight in a
      community-based sample of adult persons followed for 11 years. METHODS: A random
      sample of 4,649 persons aged 18-65 years from a general population participated
      in the DanThyr study in 1997-8. We included 2,102 individuals who participated at
      11-year follow-up, without current or former treatment for thyroid disease and
      with measurements of TSH and weight at both examinations. Multiple linear
      regression models were used, stratified by sex and adjusted for age, smoking
      status, and leisure time physical activity. RESULTS: Baseline TSH concentration
      was not associated with change in weight (women, P = 0.17; men, P = 0.72), and
      baseline body mass index (BMI) was not associated with change in TSH (women, P =
      0.21; men, P = 0.85). Change in serum TSH and change in weight were significantly
      associated in both sexes. Weight increased by 0.3 kg (95% confidence interval
      [CI] 0.1, 0.4, P = 0.005) in women and 0.8 kg (95% CI 0.1, 1.4, P = 0.02) in men
      for every one unit TSH (mU/L) increase. CONCLUSIONS: TSH levels were not a
      determinant of future weight changes, and BMI was not a determinant for TSH
      changes, but an association between weight change and TSH change was present.

PMID- 24728292
TI  - Heritability and genomics of gene expression in peripheral blood.
AB  - We assessed gene expression profiles in 2,752 twins, using a classic twin design
      to quantify expression heritability and quantitative trait loci (eQTLs) in
      peripheral blood. The most highly heritable genes (~777) were grouped into
      distinct expression clusters, enriched in gene-poor regions, associated with
      specific gene function or ontology classes, and strongly associated with disease
      designation. The design enabled a comparison of twin-based heritability to
      estimates based on dizygotic identity-by-descent sharing and distant genetic
      relatedness. Consideration of sampling variation suggests that previous
      heritability estimates have been upwardly biased. Genotyping of 2,494 twins
      enabled powerful identification of eQTLs, which we further examined in a
      replication set of 1,895 unrelated subjects. A large number of non-redundant
      local eQTLs (6,756) met replication criteria, whereas a relatively small number
      of distant eQTLs (165) met quality control and replication standards. Our results
      provide a new resource toward understanding the genetic control of transcription.

PMID- 24728295
TI  - Plastic and locally adapted phenology in cambial seasonality and production of
      xylem and phloem cells in Picea abies from temperate environments.
AB  - Despite its major economic importance and the vulnerability of Picea abies (L.)
      H. Karst. to climate change, how its radial growth at intra-annual resolution is
      influenced by weather conditions in forest stands with a high production capacity
      has scarcely been explored. Between 2009 and 2011, phenological variation in
      seasonal cambial cell production (CP) was analysed in adult P. abies trees from
      three contrasting sites, differing in altitude and latitude. The results indicate
      that the timing of cambial CP is a highly synchronic process within populations
      since in all cases the cambium simultaneously started and stopped producing xylem
      and phloem cells. Our results also demonstrate that the phenology of cambial CP
      is highly variable and plastic between years, depending on seasonal temperature
      and precipitation variation. Differences among sites, however, are only partially
      explained by different environmental (elevation and altitude) and climatic
      conditions, suggesting that local adaptation may also play a decisive role in the
      strategy of P. abies for adapting wood and phloem increments to function
      optimally under local conditions. 

PMID- 24728293
TI  - Severe osteoarthritis of the hand associates with common variants within the
      ALDH1A2 gene and with rare variants at 1p31.
AB  - Osteoarthritis is the most common form of arthritis and is a major cause of pain
      and disability in the elderly. To search for sequence variants that confer risk
      of osteoarthritis of the hand, we carried out a genome-wide association study
      (GWAS) in subjects with severe hand osteoarthritis, using variants identified
      through the whole-genome sequencing of 2,230 Icelanders. We found two
      significantly associated loci in the Icelandic discovery set: at 15q22 (frequency
      of 50.7%, odds ratio (OR) = 1.51, P = 3.99 * 10(-10)) in the ALDH1A2 gene and at
      1p31 (frequency of 0.02%, OR = 50.6, P = 9.8 * 10(-10)). Among the carriers of
      the variant at 1p31 is a family with several members in whom the risk allele
      segregates with osteoarthritis. The variants within the ALDH1A2 gene were
      confirmed in replication sets from The Netherlands and the UK, yielding an
      overall association of OR = 1.46 and P = 1.1 * 10(-11) (rs3204689). 

PMID- 24728294
TI  - Association of a germline copy number polymorphism of APOBEC3A and APOBEC3B with
      burden of putative APOBEC-dependent mutations in breast cancer.
AB  - The somatic mutations in a cancer genome are the aggregate outcome of one or more
      mutational processes operative through the lifetime of the individual with
      cancer. Each mutational process leaves a characteristic mutational signature
      determined by the mechanisms of DNA damage and repair that constitute it. A role
      was recently proposed for the APOBEC family of cytidine deaminases in generating
      particular genome-wide mutational signatures and a signature of localized
      hypermutation called kataegis. A germline copy number polymorphism involving
      APOBEC3A and APOBEC3B, which effectively deletes APOBEC3B, has been associated
      with modestly increased risk of breast cancer. Here we show that breast cancers
      in carriers of the deletion show more mutations of the putative APOBEC-dependent
      genome-wide signatures than cancers in non-carriers. The results suggest that the
      APOBEC3A-APOBEC3B germline deletion allele confers cancer susceptibility through
      increased activity of APOBEC-dependent mutational processes, although the
      mechanism by which this increase in activity occurs remains unknown. 

PMID- 24728296
TI  - PtrKOR1 is required for secondary cell wall cellulose biosynthesis in Populus.
AB  - KORRIGAN (KOR), encoding an endo-1,4-beta-glucanase, plays a critical role in the
      cellulose synthesis of plant cell wall formation. KOR sequence orthologs are
      duplicated in the Populus genome relative to Arabidopsis. This study reports an
      expression analysis of the KOR genes in Populus. The five PtrKOR genes displayed
      different expression patterns, suggesting that they play roles in different
      developmental processes. Through RNAi suppression, results demonstrated that
      PtrKOR1 is required for secondary cell wall cellulose formation in Populus.
      Together, the results suggest that the PtrKOR genes may play distinct roles in
      association with cell wall formation in different tissues. 

PMID- 24728297
TI  - Morbidity and outcomes of foreign travelers in Zakynthos island, Greece: a
      retrospective study.
AB  - BACKGROUND: Although there is satisfactory recording of diseases affecting
      travelers visiting developing countries, little is known regarding morbidity of
      travelers when visiting developed countries. We sought to evaluate the morbidity
      of foreign travelers in Zakynthos, a popular Greek island attracting large number
      of foreign tourists every summer. METHODS: Data from foreign travelers that
      accommodated in Zakynthos and sought medical services from the private offices of
      Zante Medical Care from May 1 to October 30 2012 were retrospectively analyzed.
      RESULTS: Two thousand six hundred and eighty-eight patients were included in the
      study. The mean age (+/- SD) of the patients whom the age was recorded was 29.6
      (+/- 18.3) and 51.5% of them were from 18 to 40 years old. Disorders of the
      respiratory tract (32.7%), dermatologic conditions (21.1%), musculoskeletal
      injuries (16.4%), and gastrointestinal disorders (16.3%) were the four most
      prevalent clinical categories among patients. Ear disorder was the most common
      syndromic description (14.5%) among which 81.2% were ear infections; otitis
      externa and otitis media were diagnosed in 8.5% and 3.3% patients in total. The
      most common specific diagnosis was gastroenteritis (14.3%). Insect bite and
      sunburn were the most common diagnosis (6.5% and 3.8%, respectively) among
      patients with a dermatologic condition. Ear infection was the most common
      diagnosis in pediatric patients. CONCLUSION: Disorders mainly of the upper
      respiratory tract were the predominant causes of illness among foreign travelers
      in Zakynthos. Traveler's diarrhea was the most common specific diagnosis but the
      prevalence within the total population was not very high.

PMID- 24728298
TI  - Lanthanoid containing phosphotungstates: the syntheses, crystal structure,
      electrochemistry, photoluminescence and magnetic properties.
AB  - A series of ten mononuclear lanthanoid containing phosphotungstate clusters were
      synthesized by the reaction of the dilacunary ligand [P2W19O69(H2O)](14-) with
      Ln(NO3)3.xH2O in a potassium acetate buffer (pH 4.8), leading to the formation of
      Peacock and Weakley type dimers [Ln(PW11O39)2](11-) (Ln = Pr(3+) (1), Nd(3+) (2),
      Eu(3+) (3), Gd(3+) (4), Tb(3+) (5), Dy(3+) (6), Ho(3+) (7), Er(3+) (8), Tm(3+)
      (9), and Yb(3+) (10)). All isostructural molecular clusters were structurally
      characterized using various analytical techniques like FT-IR, (31)P NMR
      spectroscopy, photoluminescence and solid state UV/vis, electrochemistry,
      magnetism and single crystal X-ray diffraction. The compounds crystallize as
      mixed potassium/caesium or potassium salts K11[Ln(PW11O39)2].xH2O (Ln = Pr(3+)
      (1a), Nd(3+) (2a), Eu(3+) (3a), Gd(3+) (4a), Tb(3+) (5a), Dy(3+) (6a), Ho(3+)
      (7a), Er(3+) (8a), and Tm(3+) (9a), in the monoclinic crystal system, space group
      P21/c (14) with the exception of the Gd(4a) and Ho(7a) complexes which
      crystallize in the triclinic system, space group P1[combining macron]. The
      prominent effect of the paramagnetic lanthanoid ion along the group on the
      monolacunary Keggin unit (alpha-PW11O39) was illustrated by FT-IR and (31)P NMR
      spectroscopy. This is attributed to its small size and high charge density
      (lanthanoid contraction). The photoluminescence of the molecular clusters Eu(3a),
      Dy(6a) and Ho(7a) was studied at room temperature at different excitation
      wavelengths and shows interesting photochromic properties. The voltammetric
      patterns associated with the W-centers in the cluster series have enough distinct
      features to allow us to establish the relative basicity of the reduced
      polyoxometalates: {PW11} > Tm(9a) > Eu(4a) ~ Tb(5a) ~ Ho(7a) > Gd(4a) ~ Dy(6a) ~
      Er(8a). Among the lanthanoid cations, just the Eu(3+) centre turned out to be
      electroactive, as expected. The magnetic measurement of Gd(4a) shows the
      paramagnetic behaviour of the material.

PMID- 24728299
TI  - [Update on gonarthritis. Conservative and operative treatment procedures].

PMID- 24728300
TI  - [Operative therapy of isolated patellofemoral arthritis. Biomechanics as a
      guide].
AB  - BACKGROUND: The treatment of patellofemoral arthritis places high demands on
      orthopedists. The exact analysis of the underlying pathobiomechanical
      relationships is the basis for every therapy decision. METHODS: Soft tissue
      procedures, such as medial patellofemoral ligament (MPFL) reconstruction for
      stabilization and bone interventions for alignment optimization (e.g. tuberosity
      transfer and corrective osteotomy) can play a role in treatment. In cases of
      advanced patellofemoral arthrosis these interventions can be used as well as in
      combination with partial joint replacement. For the choice of implant the use of
      anatomical prosthesis types is recommended because with these components the
      number of additional procedures can be reduced. CONCLUSION: The success of
      patellofemoral prosthetics depends mainly on the recognition of biomechanical
      deviations. If these can be corrected the risk of implant failure can be reduced.

PMID- 24728301
TI  - Downregulation of the CXCR4 receptor inhibits cervical carcinoma metastatic
      behavior in vitro and in vivo.
AB  - Cervical carcinoma is frequently diagnosed among women, particularly in low and
      middle income countries. In this study, we investigated the role of the SDF
      1/CXCR4 axis during cervical carcinoma growth and progression in vitro and in
      vivo. Downregulation of CXCR4 receptor using an RNA interference system led to
      almost complete inhibition of the receptor expression, activation and function.
      CXCR4 receptor silencing led to decreased ability to signal, to induce migration
      and to form holoclone-like colonies, with no influence on viability/proliferation
      of the cells. CXCR4-deficient cells had also significantly lower levels of MMP-9.
      Interestingly, downregulation of CXCR4 expression resulted in reduced tumor
      growth in vivo. Tumors generated by CXCR4-deficient cells had also lower
      expression of the proliferation marker Ki-67 and decreased ability to engraft
      into lungs and spleen. Taken together, our results indicate that CXCR4 receptor
      may play an important role during cervical carcinoma invasion. In our study CXCR4
      influenced invasive properties of cervical carcinoma cells both in vitro and in
      vivo. 

PMID- 24728302
TI  - Higher prevalence of migraine in essential tremor: a case-control study.
AB  - BACKGROUND: The existence of an association between migraine and essential tremor
      has long been controversial. The prevalence of migraine in essential tremor
      patients was surveyed to explore the association between the two diseases.
      METHODS: A case-control clinical study was conducted to investigate the
      prevalence of migraine in 150 consecutive essential tremor patients and in 150
      matched controls without tremor. Detailed information about essential tremor and
      migraine was obtained using a structured questionnaire at a face-to-face
      interview. Moreover, a functional variant of the dopamine receptor D3 gene
      (Ser9Gly, rs6280) was studied in 46 essential tremor patients with and without
      migraine using direct sequencing analysis. RESULTS: The prevalence of lifetime
      migraine in essential tremor patients was significantly higher than that in
      controls (22.0% vs. 12.7%; p=0.035; odds ratio=1.95; 95% confidence interval=1.05
      3.60). No significant difference was found in the migraine features between the
      essential tremor and control groups and most tremor characteristics were no
      different in essential tremor patients with and without migraine. A higher male
      prevalence of essential tremor patients without migraine was observed. Moreover,
      44 of 46 (95.7%) essential tremor patients had the dopamine receptor D3 Ser9Gly
      variant, but no significant difference was found in the frequencies of the
      variant between essential tremor patients with and without migraine (87.5% vs.
      100.0%; p=0.22). CONCLUSION: Our data suggest that essential tremor patients have
      a higher risk of lifetime migraine than do controls and the dopamine receptor D3
      Ser9Gly variant may be lower in essential tremor with migraine than the general
      essential tremor patients.

PMID- 24728303
TI  - Movement disorders associated with spontaneous CSF leaks: a case series.
AB  - IMPORTANCE AND OBJECTIVE: Headache is the most common symptom in spontaneous CSF
      leaks, frequently associated with additional manifestations. Herein, attention is
      drawn to movement disorder as a notable manifestation of spontaneous CSF leaks.
      DESIGN: Four women and one man (ages 51-78 years) with spontaneous CSF leaks and
      movement disorders were evaluated clinically and by pertinent neuroimaging
      studies with follow-up of one to seven years (mean 3.2 years). RESULTS: The
      movement disorder consisted of choreiform movements in two patients, torticollis
      in one, mixed tremor in one, and parkinsonism in one. All except the last patient
      had headaches (orthostatic in one, Valsalva maneuver-induced in one, both
      orthostatic and Valsalva-induced in two, lingering low-grade headache in one).
      Diffuse pachymeningeal enhancement and sinking of the brain was noted in all. CT
      myelography showed definite CSF leak in three and equivocal leak in one, while no
      leak could be located in the fifth patient. Two patients improved over time with
      complete resolution of the movement disorder. One responded to epidural blood
      patch with complete resolution of his choreiform movements. Two patients required
      surgery and epidural blood patches. Results were drastic but nondurable in one,
      while complete recovery was achieved in the other. CONCLUSION: Movement disorders
      are uncommon in spontaneous CSF leaks but occasionally can be one of the major
      components of the clinical presentation.

PMID- 24728304
TI  - Thickening of the somatosensory cortex in migraine without aura.
AB  - OBJECTIVE: We aimed to explore cortical thickness abnormalities in a homogeneous
      group of patients with migraine without aura and to delineate possible
      relationships between cortical thickness changes and clinical variables. METHODS:
      Fifty-six female migraine patients without aura and T2-visible white matter
      hyperintensities and 34 female controls were scanned on a 3T magnetic resonance
      imager. Cortical thickness was estimated and compared between patients and
      controls using a whole-brain vertex-by-vertex analysis. Correlation analysis was
      conducted between cortical thickness of significant clusters and clinical
      variables. RESULTS: Compared to controls, migraine patients had cortical
      thickening in left rostral middle frontal gyrus and bilateral post-central gyri.
      Region-of-interest analysis revealed cortical thickening of bilateral post
      central gyri in migraine patients relative to controls. The average thickness of
      bilateral post-central gyri positively correlated with disease duration as well
      as estimated lifetime headache frequency. CONCLUSIONS: We have provided evidence
      for interictal cortical abnormalities of thickened prefrontal cortex and
      somatosensory cortex in female migraine patients without aura. Our findings of
      greater thickening of the somatosensory cortex in relation to increasing disease
      duration and increasing headache frequency suggest that repeated migraine attacks
      over time may lead to structural changes of the somatosensory cortex through
      increased noxious afferent input within the trigemino-thalamo-cortical pathway in
      migraine.

PMID- 24728305
TI  - ADAM33 gene polymorphisms are associated with the risk of idiopathic pulmonary
      fibrosis.
AB  - BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is characterized by progressive
      dyspnea and worsening lung function due to remodeling of the lung, including
      epithelial mesenchymal transition. ADAM33 is a disintegrin and metalloprotease
      domain-containing protein, which may be related to lung fibrosis by exerting
      angiogenesis and remodeling of the lung. Thus, we evaluated the association of
      single-nucleotide polymorphisms (SNPs) of ADAM33 with the risk of IPF. METHODS: A
      total of 237 patients with IPF and 183 healthy subjects participated in the
      present study. Nine polymorphisms were selected. Genotyping was performed by
      single-base extension. Polymorphisms and haplotypes were analyzed for
      associations with the risk of IPF using multiple logistic regression models
      controlling for age, gender, and smoking status as covariates. RESULTS: All SNPs
      were in Hardy-Weinberg equilibrium. The minor allele frequency (MAF) of
      rs628977G>A in intron 21 was significantly lower in subjects with surgical IPF
      than in normal controls in the recessive model [33.2 vs. 38.0 %, p = 0.02, OR =
      0.40 (0.19-0.84)]. When the subjects with clinical IPF were included, the
      difference in MAF persisted with a p value of 0.03 [OR = 0.50 (0.27-0.94)].
      CONCLUSIONS: ADAM33 rs628977G>A was marginally associated with a decreased risk
      of IPF in a recessive model.

PMID- 24728306
TI  - BMPR2 germline mutation in chronic thromboembolic pulmonary hypertension.
AB  - INTRODUCTION: Heterozygous germline mutations of the bone morphogenetic protein
      type II receptor (BMPR2) gene BMPR2 are the most important predisposing factors
      for heritable pulmonary arterial hypertension. BMPR2 mutation was occasionally
      reported in pulmonary veno-occlusive disease, appetite suppressant-related
      pulmonary arterial hypertension (PAH), and PAH with congenital heart disease.
      MATERIALS AND METHODS: In this study we identified a missense mutation (c.2296A >
      G) located in BMPR2 exon 12 in a patient with chronic thromboembolic pulmonary
      hypertension (CTEPH). CONCLUSION: It is the first report of a BMPR2 mutation in
      CTEPH. Our study provides innovative insight into etiology of CTEPH. The genetic
      predisposing factor is an important component in the process of this CTEPH
      patient.

PMID- 24728307
TI  - The versatility of furfuryl alcohols and furanoxonium ions in synthesis.
AB  - Substituted furfuryl alcohols are extraordinarily versatile starting materials in
      synthesis. They are precursors to furanoxonium ion intermediates which are
      implicated in the Piancatelli reaction (leading to 2-cyclopentenones) and in the
      synthesis of novel dihydrofuran-based exo enol ether/cyclic ketal natural
      products. They are also intermediates in a recently discovered (4+3)
      cycloaddition reaction with 1,3-dienes leading to furan ring-fused cycloheptenes.
      Here we provide a perspective on recent developments in these areas of synthesis,
      alongside recent applications of the Achmatowicz reaction and [5+2] cycloaddition
      reactions of the resulting oxidopyrylium ions. 

PMID- 24728309
TI  - Role of dopamine in distal retina.
AB  - Dopamine is the most abundant catecholamine in the vertebrate retina. Despite the
      description of retinal dopaminergic cells three decades ago, many aspects of
      their function in the retina remain unclear. There is no consensus among the
      authors about the stimulus conditions for dopamine release (darkness, steady or
      flickering light) as well as about its action upon the various types of retinal
      cells. Many contradictory results exist concerning the dopamine effect on the
      gross electrical activity of the retina [reflected in electroretinogram (ERG)]
      and the receptors involved in its action. This review summarized current
      knowledge about the types of the dopaminergic neurons and receptors in the retina
      as well as the effects of dopamine receptor agonists and antagonists on the light
      responses of photoreceptors, horizontal and bipolar cells in both nonmammalian
      and mammalian retina. Special focus of interest concerns their effects upon the
      diffuse ERG as a useful tool for assessment of the overall function of the distal
      retina. An attempt is made to reveal some differences between the dopamine
      actions upon the activity of the ON versus OFF channel in the distal retina. The
      author has included her own results demonstrating such differences. 

PMID- 24728308
TI  - B Lymphocyte Stimulator (BLyS) is expressed in human adipocytes in vivo and is
      related to obesity but not to insulin resistance.
AB  - Inflammation and metabolism have been shown to be evolutionary linked and
      increasing evidence exists that pro-inflammatory factors are involved in the
      pathogenesis of obesity and type 2 diabetes. Until now, most data suggest that
      within adipose tissue these factors are secreted by cells of the innate immune
      system, e. g. macrophages. In the present study we demonstrate that B lymphocyte
      stimulator (BLyS) is increased in human obesity. In contrast to several pro
      inflammatory factors, we found the source of BLyS in human adipose tissue to be
      the adipocytes rather than immune cells. In grade 3 obese human subjects,
      expression of BLyS in vivo in adipose tissue is significantly increased
      (p<0.001). Furthermore, BLyS serum levels are elevated in grade 3 human obesity
      (862.5+222.0 pg/ml vs. 543.7+60.7 pg/ml in lean controls, p<0.001) and are
      positively correlated to the BMI (r = 0.43, p<0.0002). In the present study,
      bariatric surgery significantly altered serum BLyS concentrations. In contrast,
      weight loss due to a very-low-calorie-formula-diet (800 kcal/d) had no such
      effect. To examine metabolic activity of BLyS, in a translational research
      approach, insulin sensitivity was measured in human subjects in vivo before and
      after treatment with the human recombinant anti-BLyS antibody belimumab. Since
      BLyS is known to promote B-cell proliferation and immunoglobulin secretion, the
      present data suggest that adipocytes of grade 3 obese human subjects are able to
      activate the adaptive immune system, suggesting that in metabolic inflammation in
      humans both, innate and adaptive immunity, are of pathophysiological relevance.

PMID- 24728311
TI  - [Sexual and reproductive health in the context of the undergraduate medical
      course].

PMID- 24728310
TI  - Percutaneous grafting with bone marrow autologous concentrate for open tibia
      fractures: analysis of forty three cases and literature review.
AB  - PURPOSE: Tibial fractures are the most common lower limb fractures. Some criteria
      such as open fractures and increasing open stage are known to be associated with
      high delayed union and pseudarthrosis rate. In cases of delayed or nonunion,
      classical treatment is autologous cancelous bone graft which is associated with
      high morbidity rate. The ideal treatment would be a percutaneous harvesting and
      grafting technique. As bone marrow autologous concentrate (BMAC) presents both
      advantages, we evaluated this technique from 2002 to 2007. METHODS: This was a
      retrospective study of 43 cases of open tibial fractures with initial surgical
      treatment. The criteria of inclusion were open fracture and nonunion, delayed
      union or suspicion of delayed union. RESULTS: In 23 cases (53.5 %) BMAC was
      successful. The success group had received significantly more CFU-F than the
      failure group (469 vs 153.10(3), p = 0.013). A threshold of 360.10(3) CFU-F
      grafted could be established over which there was 100 % success. BMAC done before
      110 days after fracture had 47 % success and BMAC done since 110 days after
      fracture had 73 % success. BMAC success rate decreased with increasing initial
      fracture skin open stage. There was no BMAC success in cases of a fracture with a
      remaining gap of more than 4 mm. We had no complications with the technique at
      the iliac harvesting zone and tibia injection point. CONCLUSION: BMAC is a
      technique that should be considered as one of the different alternatives for
      management of long-bone delayed and nonunion because of its effectiveness, low
      complication rate, preservation of bone stock and low cost.

PMID- 24728312
TI  - [Microbial etiology and susceptibility of community urinary tract infections
      during pregnancy in the south of Brazil].
AB  - PURPOSE: Urinary tract infection (UTI) is one of the most common conditions
      during pregnancy. The aim of this study was to assess the prevalence of germs and
      the antimicrobial susceptibility profile in urine culture isolates from pregnant
      patients treated at a tertiary maternity hospital in Porto Alegre, Brazil.
      METHODS: A cross-sectional, retrospective and descriptive study was carried out
      at Hospital Femina, a leading institution in prenatal, birth and postnatal
      healthcare in the city of Porto Alegre, Brazil. A total of 482 microbial
      community results were analyzed out of 1,558 positive urine cultures of pregnant
      women in all gestational ages treated at Femina Hospital between January 2007 and
      July 2013. RESULTS: The susceptibility pattern presented in this research shows
      that the choice for UTI treatment during pregnancy should be nitrofurantoin (for
      uncomplicated infections) or second-generation cephalosporins such as cefuroxime
      (for uncomplicated and complicated infections), over ampicillin, first-generation
      cephalosporins and sulfamethoxazole/trimethoprim. CONCLUSION: Empirical treatment
      for UTI in pregnancy should be started according to the susceptibility patterns
      described in the literature and re-analyzed after the results of the urine
      culture.

PMID- 24728313
TI  - [Impact of sexual and reproductive health theme insertion in the undergraduate
      medical].
AB  - PURPOSE: To evaluate the impact of sexual and reproductive health theme insertion
      in the undergraduate medical curriculum at a Brazilian public university.
      METHODS: We developed an instrument for cognitive assessment in sexual and
      reproductive health based on the subjects addressed in the optional curriculum
      component Reproductive Health, resulting in an objective multiple choice test
      containing 27 items. The selected topics were: human, sexual and reproductive
      rights (HSRR), sexuality, institutional violence, gender, sexual violence,
      conception, contraception, abortion/legal interruption of pregnancy, maternal
      mortality and sexually transmitted infections (STIs) - HIV/AIDS. The subjects
      were grouped into three dimensions of knowledge: HSRR, legal/institutional and
      biomedical. Two multivariate models were adjusted in the analysis of covariance.
      RESULTS: The study included 183 students, 127 of the group who took the elective
      curriculum course reproductive health (RH Group) and 56 who did not (Non-RH
      Group). Ninety-six students (52.5%) were males and 87 (47.5%) were females. Mean
      age was 24.7+/-1.9 years for the RH Group and 24.4+/-2.6 for the Non-RH Group.
      The average performance of the SR Group was higher than that of Non-RH subjects
      regarding the following subjects: HSRR, sexuality, institutional violence, sexual
      violence, abortion/legal interruption, and STDs - HIV/AIDS. There was no gender
      difference in performance, except for the theme maternal mortality, in which
      males scored worse than females (6.9+/-0.2 and 7.8+/-0.2, respectively; p<0.05).
      CONCLUSIONS: The participation of students in the elective curriculum component
      Reproductive Health was associated with better performance in some dimensions of
      cognitive assessment, suggesting a positive impact of this initiative on general
      medical education.

PMID- 24728314
TI  - Chromosomal abnormalities in couples with recurrent first trimester abortions.
AB  - PURPOSE: To investigate the prevalence of chromosomal abnormalities in couples
      with two or more recurrent first trimester miscarriages of unknown cause.
      METHODS: The study was conducted on 151 women and 94 partners who had an
      obstetrical history of two or more consecutive first trimester abortions (1-12
      weeks of gestation). The controls were 100 healthy women without a history of
      pregnancy loss. Chromosomal analysis was performed on peripheral blood
      lymphocytes cultured for 72 hours, using Trypsin-Giemsa (GTG) banding. In all
      cases, at least 30 metaphases were analyzed and 2 karyotypes were prepared, using
      light microscopy. The statistical analysis was performed using the Student t-test
      for normally distributed data and the Mann-Whitney test for non-parametric data.
      The Kruskal-Wallis test or Analysis of Variance was used to compare the mean
      values between three or more groups. The software used was Statistical Package
      for the Social Sciences (SPSS), version 17.0. RESULTS: The frequency of
      chromosomal abnormalities in women with recurrent miscarriages was 7.3%,
      including 4.7% with X-chromosome mosaicism, 2% with reciprocal translocations and
      0.6% with Robertsonian translocations. A total of 2.1% of the partners of women
      with recurrent miscarriages had chromosomal abnormalities, including 1% with X
      chromosome mosaicism and 1% with inversions. Among the controls, 1% had
      mosaicism. CONCLUSION: An association between chromosomal abnormalities and
      recurrent miscarriage in the first trimester of pregnancy (OR=7.7; 95%CI 1.2-
      170.5) was observed in the present study. Etiologic identification of genetic
      factors represents important clinical information for genetic counseling and
      orientation of the couple about the risk for future pregnancies and decreases the
      number of investigations needed to elucidate the possible causes of miscarriages.

PMID- 24728315
TI  - [Axillary lymph node aspiration guided by ultrasound is effective as a method of
      predicting lymph node involvement in patients with breast cancer?].
AB  - PURPOSE: To assess the feasibility and diagnostic accuracy of preoperative
      ultrasound combined with ultrasound-guided fine-needle aspiration (US-FNA)
      cytology and clinical examination of axillary lymph node in patients with breast
      cancer. METHODS: In this prospective study, 171 axillae of patients with breast
      cancer were evaluated by clinical examination and ultrasonography (US) with and
      without fine needle aspiration (FNA). Lymph nodes with maximum ultrasonographic
      cortical thickness > 2.3 mm were considered suspicious and submitted to US-FNA.
      RESULTS: Logistic regression analysis showed no statistically significant
      correlation between clinical examination and pathologically positive axillae.
      However, in axillae considered suspicious by ultrasonography, the risk of
      positive anatomopathological findings increased 12.6-fold. Cohen's Kappa value
      was 0.12 for clinical examination, 0.48 for US, and 0.80 for US-FNA. Accuracy was
      61.4% for clinical examination, 73.1% for US and 90.1% for US-FA. Receiver
      Operating Characteristics (ROC) analysis demonstrated that a cortical thickness
      of 2.75 mm corresponded to the highest sensitivity and specificity in predicting
      axillary metastasis (82.7 and 82.2%, respectively). CONCLUSIONS: Ultrasonography
      combined with fine-needle aspiration is more accurate than clinical examination
      in assessing preoperative axillary status in women with breast cancer. Those who
      are US-FNA positive can be directed towards axillary lymph node dissection
      straight away, and only those who are US-FNA negative should be considered for
      sentinel lymph node biopsy.

PMID- 24728316
TI  - [Laparoscopy for diagnosis and treatment of adnexal masses].
AB  - PURPOSE: To assess clinical factors, histopathologic diagnoses, operative time
      and differences in complication rates between women undergoing laparoscopy or
      laparotomy to diagnose and treat an adnexal mass and their association with
      laparoscopy failure. METHODS: In this prospective study, 210 women were invited
      to participate and 133 of them were included. Eighty-eight women underwent
      laparotomy and 45 underwent laparoscopy. Fourteen of the 45 laparoscopies were
      converted to laparotomy intraoperatively. We assessed whether age, body mass
      index (BMI), previous abdominal surgeries, CA-125, Index of Risk of Malignancy
      (IRM), tumor diameter, histological diagnosis, operative time and surgical
      complication rates differed between the laparoscopy group and the group converted
      to laparotomy and whether those factors were associated with conversion of
      laparoscopy to laparotomy. We also assessed surgical logs to evaluate the
      reasons, as stated by the surgeons, to convert a laparoscopy to laparotomy.
      RESULTS: In this research, 30% of the women had malignant tumors. CA-125, IRM,
      tumor diameter and operative times were higher for the laparotomy group than the
      laparoscopy group. Complication rates were similar for both groups and also for
      the successful laparoscopy and unsuccessful laparoscopy groups. The surgical
      complication rate in women with benign tumors was lower for the laparoscopy group
      than for the laparotomy group. The factors associated with conversion to
      laparotomy were tumor diameter and malignancy. During laparoscopy, adhesions a
      large tumor diameter were the principal causes of conversion. CONCLUSION: This
      study suggests that laparoscopy for the diagnosis and treatment of adnexal masses
      is safe and does not increase complication rates even in patients who need
      conversion to laparotomy. However, when doubt about the safety of the procedure
      and about the presence of malignancy persists, consultation with an expert
      gynecology-oncologist with experience in advanced laparoscopy is recommended. A
      large tumor diameter was associated with the necessity of conversion to
      laparotomy.

PMID- 24728317
TI  - [Translation and validation of the Pregnancy and Sexual Function Questionnaire
      (PSFQ)].
AB  - PURPOSE: To adapt the Pregnancy and Sexual Function Questionnaire (PSFQ) for use
      in Brazil and to evaluate its psychometric properties. METHODS: An adaptation and
      validation study was performed with women in the last trimester of pregnancy
      living in Rio Branco, Acre. The questionnaire was translated into Portuguese,
      reviewed and evaluated by specialists, and a pretest was carried out. Construct
      validity was evaluated by factor analysis; internal consistency was estimated by
      Cronbach's alpha coefficient and MacDonald's omega, and reproducibility was
      evaluated by the kappa statistics and test-retest in a sample of pregnant women.
      RESULTS: Factor analysis identified the following six domains: subjectivity, pain
      and discomfort; frequency and receptivity; desirability; satisfaction; orgasm;
      and stimulus. The internal consistency by Cronbach's alpha was 0.6, while
      MacDonald's omega was 0.7. The kappa value was higher than 0.7 in all questions.
      CONCLUSION: The Portuguese version of the PSFQ was considered to be adequate for
      evaluating sexual function during pregnancy.

PMID- 24728318
TI  - Mondor's disease in puerperium: case report.
AB  - Mondor's disease is a rare entity characterized by sclerosing thrombophlebitis
      classically involving one or more of the subcutaneous veins of the breast and
      anterior chest wall. It is usually a self-limited, benign condition, despite of
      rare cases of association to cancer. We present the case of a 32 year-old female,
      breast-feeding, who went to emergency due to left mastalgia for the past week.
      She was taking antibiotics and non-steroidal anti-inflammatory drugs, previously
      prescribed for suspicious of mastitis, for three days, with no clinical
      improvement. Physical examination showed an enlarged left breast, an axillary
      lump and a painful cord-like structure in the upper outer quadrant of the same
      breast. Ultrasound scan showed a markedly dilated superficial vein in the upper
      outer quadrant of left breast. The patient was given a ventropic therapy and was
      kept in anti-inflammatory, with progressive pain improvement. Ultrasound control
      was performed after four weeks, showing reperfusion.

PMID- 24728319
TI  - Synthesis of new anionic carbosilane dendrimers via thiol-ene chemistry and their
      antiviral behaviour.
AB  - A synthetic strategy has been developed for the preparation of anionic
      carbosilane dendrimers bearing sulfonate or carboxylate groups at their periphery
      by means of thiol-ene chemistry. It offers significant advantages, such as milder
      reaction conditions, shorter reaction times and more facile purification methods,
      when compared with other synthetic protocols used previously, e.g.
      hydrosilylation followed by a Michael-type addition or azide-alkyne coupling
      reactions. Molecular dynamics simulations of the second generation anionic
      dendrimers addressing shape and size effects of the terminal groups and
      conformational variability indicated that the core eccentricity and flexibility
      might need to be taken into account for toxicity and interaction with viral
      and/or cellular receptors, respectively. The biocompatibility of anionic
      carbosilane dendrimers has been explored showing differences between silicon
      cored and polyphenoxo-cored dendrimers. In addition, silicon-cored dendrimers
      achieved 85-90% of HIV inhibition without inducing inflammation or vaginal
      irritation in mice, which makes them likely candidates for readily available,
      good and safe topical vaginal microbicides against HIV. 

PMID- 24728320
TI  - Continuous increase of cardiovascular diseases, diabetes, and non-HIV related
      cancers as causes of death in HIV-infected individuals in Brazil: an analysis of
      nationwide data.
AB  - INTRODUCTION: After antiretroviral therapy (ART) became available, there was a
      decline in the number of deaths in persons infected with HIV. Thereafter, there
      was a decrease in the proportion of deaths attributed to opportunistic infections
      and an increase in the proportion of deaths attributed to chronic comorbidities.
      Herein we extend previous observations from a nationwide survey on temporal
      trends in causes of death in HIV-infected patients in Brazil. METHODS: We
      describe temporal trends in causes of death among adults who had HIV/AIDS listed
      in the death certificate to those who did not. All death certificates issued in
      Brazil from 1999 to 2011 and listed in the national mortality database were
      included. Generalized linear mixed-effects logistic models were used to study
      temporal trends in proportions. RESULTS: In the HIV-infected population, there
      was an annual adjusted average increase of 6.0%, 12.0%, 4.0% and 4.1% for cancer,
      external causes, cardiovascular diseases (CVD) and diabetes mellitus (DM),
      respectively, compared to 3.0%, 4.0%, 1.0% and 3.9%, in the non-HIV group. For
      tuberculosis (TB), there was an adjusted average increase of 0.3%/year and a
      decrease of 3.0%/year in the HIV and the non-HIV groups, respectively. Compared
      to 1999, the odds ratio (OR) for cancer, external causes, CVD, DM, or TB in the
      HIV group were, respectively, 2.31, 4.17, 1.76, 2.27 and 1.02, while for the non
      HIV group, the corresponding OR were 1.31, 1.63, 1.14, 1.62 and 0.67.
      Interactions between year as a continuous or categorical variable and HIV were
      significant (p<0.001) for all conditions, except for DM when year was considered
      as a continuous variable (p = 0.76). CONCLUSIONS: Non HIV-related co-morbidities
      continue to increase more rapidly as causes of death among HIV-infected
      individuals than in those without HIV infection, highlighting the need for
      targeting prevention measures and surveillance for chronic diseases among those
      patients.

PMID- 24728321
TI  - COLD-PCR amplification of bisulfite-converted DNA allows the enrichment and
      sequencing of rare un-methylated genomic regions.
AB  - Aberrant hypo-methylation of DNA is evident in a range of human diseases
      including cancer and diabetes. Development of sensitive assays capable of
      detecting traces of un-methylated DNA within methylated samples can be useful in
      several situations. Here we describe a new approach, fast-COLD-MS-PCR, which
      amplifies preferentially un-methylated DNA sequences. By employing an appropriate
      denaturation temperature during PCR of bi-sulfite converted DNA, fast-COLD-MS-PCR
      enriches un-methylated DNA and enables differential melting analysis or bisulfite
      sequencing. Using methylation on the MGMT gene promoter as a model, it is shown
      that serial dilutions of controlled methylation samples lead to the reliable
      sequencing of un-methylated sequences down to 0.05% un-methylated-to-methylated
      DNA. Screening of clinical glioma tumor and infant blood samples demonstrated
      that the degree of enrichment of un-methylated over methylated DNA can be
      modulated by the choice of denaturation temperature, providing a convenient
      method for analysis of partially methylated DNA or for revealing and sequencing
      traces of un-methylated DNA. Fast-COLD-MS-PCR can be useful for the detection of
      loss of methylation/imprinting in cancer, diabetes or diet-related methylation
      changes. 

PMID- 24728322
TI  - Extraordinary absorption of sound in porous lamella-crystals.
AB  - We present the design of a structured material supporting complete absorption of
      sound with a broadband response and functional for any direction of incident
      radiation. The structure which is fabricated out of porous lamellas is arranged
      into a low-density crystal and backed by a reflecting support. Experimental
      measurements show that strong all-angle sound absorption with almost zero
      reflectance takes place for a frequency range exceeding two octaves. We
      demonstrate that lowering the crystal filling fraction increases the wave
      interaction time and is responsible for the enhancement of intrinsic material
      dissipation, making the system more absorptive with less material. 

PMID- 24728325
TI  - A microporous Zn(II)-MOF with open metal sites: structure and selective
      adsorption properties.
AB  - A three-dimensional microporous framework, Zn(II)-MOF [Zn(HPyImDC)(DMA)]n (1)
      (H3PyImDC = 2-(pyridine-4-yl)-1H-4,5-imidazoledicarboxylic, DMA = N,N'
      dimethylacetamide), with open metal sites and small-sized pores, exhibits
      excellent selective capture of CO2 over N2 and CH4 at 273 K, as well as alcohols
      from water. The excellent CO2 adsorption selectivity of 1 allows its potential
      use in the capture of CO2 from industrial flue gas or the removal of CO2 from
      natural gas. More interestingly, compound represents the rare case of porous
      materials separating propanol isomers, which may be caused by the relative
      flexibility of the linear n-propanol considering that both n-propanol and i
      propanol have similar kinetic diameters.

PMID- 24728326
TI  - All-arthroscopic versus mini-open repair of small to large sized rotator cuff
      tears: a meta-analysis of clinical outcomes.
AB  - PURPOSE: The purpose of this study was to compare clinical outcomes of patients
      with full-thickness small to large sized tears undergoing all-arthroscopic versus
      mini-open rotator cuff repair. METHOD: A literature search for electronic
      databases and references for eligible studies was conducted through Medline,
      Embase and Cochrane library between 1969 and 2013. RESULTS: A total of 12
      comparative studies (n = 770 patients) were included. Pooled results showed:
      there were no differences in function outcome, pain scores, retear rate or the
      incidence of adhesive capsulitis between all arthroscopic and mini-open repair
      groups. CONCLUSIONS: There were no differences in outcomes between the
      arthroscopic and mini-open rotator cuff repair techniques, they should be
      considered alternative treatment options. LEVEL OF EVIDENCE: Level IV, Meta
      analysis.

PMID- 24728328
TI  - Exploring the electronic states of iodocarbyne: a theoretical contribution.
AB  - A manifold of electronic states correlating with the two lowest-lying
      dissociation channels of the iodocarbyne (CI) species is theoretically
      characterized for the first time in the literature. A contrast between the Lambda
      + S and the relativistic (Omega) descriptions clearly shows the effect of
      perturbations on electronic states above 20 000 cm(-1) and the potential
      difficulties to detect them experimentally. For the bound states, spectroscopic
      parameters were evaluated, as well as the dipole moment functions. Similarly to
      CO, the polarity predicted for this iodocarbyne is C(delta-)I(delta+); as
      illustrated in the text, this is also the case for the other halocarbynes. As a
      potential mechanism for the experimental spectroscopic characterization of CI, we
      suggest the radiative association between C and I atoms, with light emitted in
      the red region of the visible spectra. Transition probabilities were also
      evaluated predicting very weak intensities. For the states 1/2(II) and 3/2(II),
      we have estimated radiative lifetimes of 7.1 and 714 ms, respectively. 

PMID- 24728327
TI  - Germline variation in cancer-susceptibility genes in a healthy, ancestrally
      diverse cohort: implications for individual genome sequencing.
AB  - Technological advances coupled with decreasing costs are bringing whole genome
      and whole exome sequencing closer to routine clinical use. One of the hurdles to
      clinical implementation is the high number of variants of unknown significance.
      For cancer-susceptibility genes, the difficulty in interpreting the clinical
      relevance of the genomic variants is compounded by the fact that most of what is
      known about these variants comes from the study of highly selected populations,
      such as cancer patients or individuals with a family history of cancer. The
      genetic variation in known cancer-susceptibility genes in the general population
      has not been well characterized to date. To address this gap, we profiled the
      nonsynonymous genomic variation in 158 genes causally implicated in
      carcinogenesis using high-quality whole genome sequences from an ancestrally
      diverse cohort of 681 healthy individuals. We found that all individuals carry
      multiple variants that may impact cancer susceptibility, with an average of 68
      variants per individual. Of the 2,688 allelic variants identified within the
      cohort, most are very rare, with 75% found in only 1 or 2 individuals in our
      population. Allele frequencies vary between ancestral groups, and there are 21
      variants for which the minor allele in one population is the major allele in
      another. Detailed analysis of a selected subset of 5 clinically important cancer
      genes, BRCA1, BRCA2, KRAS, TP53, and PTEN, highlights differences between
      germline variants and reported somatic mutations. The dataset can serve a
      resource of genetic variation in cancer-susceptibility genes in 6 ancestry
      groups, an important foundation for the interpretation of cancer risk from
      personal genome sequences. 

PMID- 24728329
TI  - Head-to-head, randomised, crossover study of oral versus subcutaneous
      methotrexate in patients with rheumatoid arthritis: drug-exposure limitations of
      oral methotrexate at doses >=15 mg may be overcome with subcutaneous
      administration.
AB  - OBJECTIVE: To compare the relative bioavailability, safety and tolerability of
      oral methotrexate (MTX) and subcutaneous (SC) MTX administered via an auto
      injector (MTXAI) in patients with rheumatoid arthritis (RA). METHODS: In this
      randomised, multicenter, open-label, three-way crossover study, patients >=18
      years with adult RA undergoing treatment with MTX for >=3 months were assigned to
      receive MTX 10, 15, 20 and 25 mg weekly in a random sequence of three treatments:
      oral, SC into the abdomen and SC into the thigh. For 24 h after administration of
      each treatment, blood samples were collected for pharmacokinetic analysis and
      injection sites were assessed. RESULTS: Forty-seven patients completed the study.
      Systemic exposure of oral MTX plateaued at doses >=15 mg/week. In contrast, SC
      MTX demonstrated a linear increase in systemic exposure that was greater than
      oral MTX at each dose. No unexpected AEs were noted for either formulation.
      CONCLUSIONS: Unlike oral MTX, the systemic exposure of SC MTX did not plateau
      over the doses studied, particularly at doses >=15 mg/week. In this study, higher
      systemic MTX exposure was not associated with increases in AEs. Patients with an
      inadequate clinical response to oral MTX may benefit from higher drug exposure by
      switching to SC MTX. TRIAL REGISTRATION NUMBER: NCT01618968.

PMID- 24728330
TI  - Overweight/obesity and vitamin D deficiency contribute to the global burden of
      low back pain.

PMID- 24728331
TI  - Predicting the development of clinical arthritis in anti-CCP positive individuals
      with non-specific musculoskeletal symptoms: a prospective observational cohort
      study.
AB  - OBJECTIVES: To monitor progression to inflammatory arthritis (IA) in individuals
      with non-specific musculoskeletal (MSK) symptoms and positive anticyclic
      citrullinated peptide (anti-CCP) antibodies. To develop a pragmatic model to
      predict development of IA in this patient group. METHODS: In this prospective
      observational cohort, patients with new non-specific MSK symptoms and positive
      anti-CCP were recruited from regional primary care and secondary care referrals.
      Clinical, imaging and serological parameters were assessed at baseline. Cox
      regression analysis was performed to identify predictors of progression to IA and
      develop a risk score to stratify patients at presentation. FINDINGS: 100
      consecutive patients (73 women, mean age 51 years) were followed up for median
      19.8 months (range 0.1-69.0); 50 developed IA after a median 7.9 months (range
      0.1-52.4), 34 within 12 months. The majority (43/50) fulfilled the 2010 American
      College of Rheumatology/European League Against Rheumatism criteria for
      rheumatoid arthritis. A model for progression to IA was devised using four
      variables: tenderness of hand or foot joints, early morning stiffness >=30 min,
      high-positive autoantibodies, and positive ultrasonographic power Doppler signal.
      None of the five individuals at low risk (score 0) progressed to IA, compared
      with 31% of 29 at moderate risk (1-2) and 62% of 66 at high risk (>=3). Adding
      shared epitope increased the number at low risk (score 0-1; 0/11 progressed).
      CONCLUSIONS: In patients presenting with non-specific MSK symptoms and anti-CCP,
      the risk of progression to IA could be quantified using data available in
      clinical practice. The proposed risk score may be used to stratify patients for
      early therapeutic intervention. TRIAL REGISTRATION NUMBER: NCT02012764 at
      ClinicalTrials.gov.

PMID- 24728332
TI  - Imaging research results from the osteoarthritis initiative (OAI): a review and
      lessons learned 10 years after start of enrolment.
AB  - The Osteoarthritis Initiative (OAI) is a multicentre, prospective, observational,
      cohort study of knee osteoarthritis (OA) that began recruitment in 2004. The OAI
      provides public access to clinical and image data, enabling researchers to
      examine risk factors/predictors and the natural history of knee OA incidence and
      progression, and the qualification of imaging and other biomarkers. In this
      narrative review, we report imaging findings and lessons learned 10 years after
      enrolment has started. A literature search for full text articles published from
      the OAI was performed up to 31 December 2013 using Pubmed and the OAI web page.
      We summarise the rationale, design and imaging protocol of the OAI, and the
      history of OAI publications. We review studies from early partial, and later full
      OAI public data releases. The latter are structured by imaging method and tissue,
      reviewing radiography and then MRI findings on cartilage morphology, cartilage
      lesions and composition (T2), bone, meniscus, muscle and adipose tissue. Finally,
      analyses directly comparing findings from MRI and radiography are summarised. Ten
      years after the first participants were enrolled and first papers published, the
      OAI has become an invaluable resource to the OA research community. It has
      fuelled novel methodological approaches of analysing images, and has provided a
      wealth of information on OA pathophysiology. Continued collection and public
      release of long-term observations will help imaging measures to gain scientific
      and regulatory acceptance as 'prognostic' or 'efficacy of intervention'
      biomarkers, potentially enabling shorter and more efficient clinical trials that
      can test structure-modifying therapeutic interventions (NCT00080171). 

PMID- 24728333
TI  - Poorly controlled type 2 diabetes mellitus is associated with a decreased risk of
      incident gout: a population-based case-control study.
AB  - OBJECTIVE: The aim of this study was to explore the risk of incident gout in
      patients with type 2 diabetes mellitus (T2DM) in association with diabetes
      duration, diabetes severity and antidiabetic drug treatment. METHODS: We
      conducted a case-control study in patients with T2DM using the UK-based Clinical
      Practice Research Datalink (CPRD). We identified case patients aged >=18 years
      with an incident diagnosis of gout between 1990 and 2012. We matched to each case
      patient one gout-free control patient. We used conditional logistic regression
      analysis to calculate adjusted ORs (adj. ORs) with 95% CIs and adjusted our
      analyses for important potential confounders. RESULTS: The study encompassed 7536
      T2DM cases with a first-time diagnosis of gout. Compared to a diabetes duration
      <1 year, prolonged diabetes duration (1-3, 3-6, 7-9 and >=10 years) was
      associated with decreased adj. ORs of 0.91 (95% CI 0.79 to 1.04), 0.76 (95% CI
      0.67 to 0.86), 0.70 (95% CI 0.61 to 0.86), and 0.58 (95% CI 0.51 to 0.66),
      respectively. Compared to a reference A1C level of <7%, the risk estimates of
      increasing A1C levels (7.0-7.9, 8.0-8.9 and >=9%) steadily decreased with adj.
      ORs of 0.79 (95% CI 0.72 to 0.86), 0.63 (95% CI 0.55 to 0.72), and 0.46 (95% CI
      0.40 to 0.53), respectively. Neither use of insulin, metformin, nor sulfonylureas
      was associated with an altered risk of incident gout. CONCLUSIONS: Increased A1C
      levels, but not use of antidiabetic drugs, was associated with a decreased risk
      of incident gout among patients with T2DM.

PMID- 24728334
TI  - Recurrence or rebound of clinical relapses after discontinuation of natalizumab
      therapy in highly active MS patients.
AB  - A number of studies have reported flare-up of multiple sclerosis (MS) disease
      activity after cessation of natalizumab, increasing to a level beyond the pre
      natalizumab treatment level. Our aim was to describe the development in clinical
      disease activity following cessation of natalizumab therapy in a large unselected
      cohort of highly active patients. We studied 375 highly active patients who had
      suffered at least two significant relapses within 1 year or three relapses within
      2 years, or had been treated with mitoxantrone for highly active disease. All
      patients had discontinued therapy with natalizumab after at least 24 weeks on
      therapy, and had been followed 3-12 months (mean 8.9 months) after cessation of
      natalizumab therapy. The annualised relapse rate before start of natalizumab
      therapy was 0.94 (95 % confidence interval [CI] 0.88-1.00), 0.47 (95 % CI 0.43
      0.52) during natalizumab therapy, 0.63 (95 % CI 0.51-0.76) 1-6 months after
      natalizumab and 0.55 (95 % CI 0.42-0.70) 7-12 months after natalizumab. However,
      83 (22 %) of the patients could be classified as showing rebound of relapses,
      defined as a higher individual relapse rate after cessation of natalizumab than
      before natalizumab. These patients had a higher annualised relapse rate during
      natalizumab therapy. For the whole patient group, the relapse rate after
      discontinuation did not exceed the pre-natalizumab relapse rate at any time, but
      22 % of the patients showed rebound of relapses after discontinuation of
      natalizumab.

PMID- 24728335
TI  - The screening of Alzheimer's patients with CSF biomarkers, modulates the
      distribution of APOE genotype: impact on clinical trials.
AB  - Polymorphism of the apolipoprotein E gene (APOE) plays a role in the level of
      neuropathological lesions and in drug response in Alzheimer's disease (AD). The
      aim of this study was to investigate whether the selection of AD patients based
      on cerebrospinal fluid (CSF) biomarkers assessment may be biased by their APOE
      distribution. We studied the relationships between APOE genotype and CSF
      biomarkers levels in a total of 432 patients (AD, n = 244; non-AD, n = 188)
      explored for cognitive disorders. We studied the distribution of APOE genotypes
      among AD patient subgroups selected by various cut-offs of CSF biomarkers.
      Strategies of screening based on CSF Abeta1-42 lead to overselection of
      epsilon4/epsilon4 patients in the AD group. Screening based on tau levels did not
      change Apoe4 distribution in the AD group. CSF Abeta1-42 discriminated better AD
      patients with at least one epsilon4 than AD patients with no epsilon4. A strong
      allele-effect relationship was detected between APOE genotype and CSF amyloid
      beta (Abeta1-42) in AD patients. Selecting AD patients on CSF amyloid levels only
      may create an overselection of epsilon4/epsilon4 carriers, and might potentially
      bias the population of patients included in clinical trial studies.

PMID- 24728336
TI  - Transient and permanent neuroimaging abnormalities due to partial status
      epilepticus in a patient with corpus callosum agenesis.

PMID- 24728338
TI  - Generalization of entropy based divergence measures for symbolic sequence
      analysis.
AB  - Entropy based measures have been frequently used in symbolic sequence analysis. A
      symmetrized and smoothed form of Kullback-Leibler divergence or relative entropy,
      the Jensen-Shannon divergence (JSD), is of particular interest because of its
      sharing properties with families of other divergence measures and its
      interpretability in different domains including statistical physics, information
      theory and mathematical statistics. The uniqueness and versatility of this
      measure arise because of a number of attributes including generalization to any
      number of probability distributions and association of weights to the
      distributions. Furthermore, its entropic formulation allows its generalization in
      different statistical frameworks, such as, non-extensive Tsallis statistics and
      higher order Markovian statistics. We revisit these generalizations and propose a
      new generalization of JSD in the integrated Tsallis and Markovian statistical
      framework. We show that this generalization can be interpreted in terms of mutual
      information. We also investigate the performance of different JSD generalizations
      in deconstructing chimeric DNA sequences assembled from bacterial genomes
      including that of E. coli, S. enterica typhi, Y. pestis and H. influenzae. Our
      results show that the JSD generalizations bring in more pronounced improvements
      when the sequences being compared are from phylogenetically proximal organisms,
      which are often difficult to distinguish because of their compositional
      similarity. While small but noticeable improvements were observed with the
      Tsallis statistical JSD generalization, relatively large improvements were
      observed with the Markovian generalization. In contrast, the proposed Tsallis
      Markovian generalization yielded more pronounced improvements relative to the
      Tsallis and Markovian generalizations, specifically when the sequences being
      compared arose from phylogenetically proximal organisms. 

PMID- 24728337
TI  - A multimodal approach to understanding motor impairment and disability after
      stroke.
AB  - Many different measures have been found to be related to behavioral outcome after
      stroke. Preclinical studies emphasize the importance of brain injury and neural
      function. However, the measures most important to human outcomes remain
      uncertain, in part because studies often examine one measure at a time or enroll
      only mildly impaired patients. The current study addressed this by performing
      multimodal evaluation in a heterogeneous population. Patients (n = 36) with
      stable arm paresis 3-6 months post-stroke were assessed across 6 categories of
      measures related to stroke outcome: demographics/medical history, cognitive/mood
      status, genetics, neurophysiology, brain injury, and cortical function.
      Multivariate modeling identified measures independently related to an impairment
      based outcome (arm Fugl-Meyer motor score). Analyses were repeated (1)
      identifying measures related to disability (modified Rankin Scale score),
      describing independence in daily functions and (2) using only patients with mild
      deficits. Across patients, greater impairment was related to measures of injury
      (reduced corticospinal tract integrity) and neurophysiology (absence of motor
      evoked potential). In contrast, (1) greater disability was related to greater
      injury and poorer cognitive status (MMSE score) and (2) among patients with mild
      deficits, greater impairment was related to cortical function (greater
      contralesional motor/premotor cortex activation). Impairment after stroke is most
      related to injury and neurophysiology, consistent with preclinical studies. These
      relationships vary according to the patient subgroup or the behavioral endpoint
      studied. One potential implication of these results is that choice of biomarker
      or stratifying variable in a clinical stroke study might vary according to
      patient characteristics.

PMID- 24728339
TI  - The pattern of cytokine production in vitro induced by ancient and modern Beijing
      Mycobacterium tuberculosis strains.
AB  - It is unclear to what extent the host-responses elicited by Beijing versus non
      Beijing strains of Mycobacterium tuberculosis (MTB) contribute to the
      predominance of modern Beijing strains in Taiwan and some other Asian countries.
      The purpose of this study was to compare the expression profiles of virulence
      related genes in human monocyte-derived macrophages infected in vitro with
      Beijing (ancient and modern strains) and non-Beijing strains (EAI strains) of MTB
      that are epidemic in Taiwan. We found that modern Beijing strains induced lower
      levels of pro-inflammatory cytokines, whereas EAI strains induced higher levels.
      Notably, the most prevalent modern Beijing sub-lineage, possessing intact RD150
      and RD142 chromosomal regions, induced very low levels of pro-inflammatory
      cytokines, especially interleukin-1beta. Moreover, in an intracellular growth
      assay, the survival of the same modern Beijing strain in human monocyte-derived
      macrophages was significantly higher than that of an ancient Beijing strain and
      an EAI strain. Taken together, these results may explain why modern Beijing
      strains of MTB predominate in Taiwan. 

PMID- 24728340
TI  - TGF-beta-activated kinase 1 (TAK1) signaling regulates TGF-beta-induced WNT-5A
      expression in airway smooth muscle cells via Sp1 and beta-catenin.
AB  - WNT-5A, a key player in embryonic development and post-natal homeostasis, has
      been associated with a myriad of pathological conditions including malignant,
      fibroproliferative and inflammatory disorders. Previously, we have identified WNT
      5A as a transcriptional target of TGF-beta in airway smooth muscle cells and
      demonstrated its function as a mediator of airway remodeling. Here, we
      investigated the molecular mechanisms underlying TGF-beta-induced WNT-5A
      expression. We show that TGF-beta-activated kinase 1 (TAK1) is a critical
      mediator of WNT-5A expression as its pharmacological inhibition or siRNA-mediated
      silencing reduced TGF-beta induction of WNT-5A. Furthermore, we show that TAK1
      engages p38 and c-Jun N-terminal kinase (JNK) signaling which redundantly
      participates in WNT-5A induction as only simultaneous, but not individual,
      inhibition of p38 and JNK suppressed TGF-beta-induced WNT-5A expression.
      Remarkably, we demonstrate a central role of beta-catenin in TGF-beta-induced WNT
      5A expression. Regulated by TAK1, beta-catenin is required for WNT-5A induction
      as its silencing repressed WNT-5A expression whereas a constitutively active
      mutant augmented basal WNT-5A abundance. Furthermore, we identify Sp1 as the
      transcription factor for WNT-5A and demonstrate its interaction with beta
      catenin. We discover that Sp1 is recruited to the WNT-5A promoter in a TGF-beta
      induced and TAK1-regulated manner. Collectively, our findings describe a TAK1
      dependent, beta-catenin- and Sp1-mediated signaling cascade activated downstream
      of TGF-beta which regulates WNT-5A induction. 

PMID- 24728341
TI  - Accelerated fast spin-echo magnetic resonance imaging of the heart using a self
      calibrated split-echo approach.
AB  - PURPOSE: Design, validation and application of an accelerated fast spin-echo
      (FSE) variant that uses a split-echo approach for self-calibrated parallel
      imaging. METHODS: For self-calibrated, split-echo FSE (SCSE-FSE), extra
      displacement gradients were incorporated into FSE to decompose odd and even echo
      groups which were independently phase encoded to derive coil sensitivity maps,
      and to generate undersampled data (reduction factor up to R = 3). Reference and
      undersampled data were acquired simultaneously. SENSE reconstruction was
      employed. RESULTS: The feasibility of SCSE-FSE was demonstrated in phantom
      studies. Point spread function performance of SCSE-FSE was found to be
      competitive with traditional FSE variants. The immunity of SCSE-FSE for motion
      induced mis-registration between reference and undersampled data was shown using
      a dynamic left ventricular model and cardiac imaging. The applicability of black
      blood prepared SCSE-FSE for cardiac imaging was demonstrated in healthy
      volunteers including accelerated multi-slice per breath-hold imaging and
      accelerated high spatial resolution imaging. CONCLUSION: SCSE-FSE obviates the
      need of external reference scans for SENSE reconstructed parallel imaging with
      FSE. SCSE-FSE reduces the risk for mis-registration between reference scans and
      accelerated acquisitions. SCSE-FSE is feasible for imaging of the heart and of
      large cardiac vessels but also meets the needs of brain, abdominal and liver
      imaging.

PMID- 24728342
TI  - Plant-species diversity correlates with genetic variation of an oligophagous seed
      predator.
AB  - Several characteristics of habitats of herbivores and their food-plant
      communities, such as plant-species composition and plant quality, influence
      population genetics of both herbivores and their host plants. We investigated how
      different ecological and geographic factors affect genetic variation in and
      differentiation of 23 populations of the oligophagous seed predator Lygaeus
      equestris (Heteroptera) in southwestern Finland and in eastern Sweden. We tested
      whether genetic differentiation of the L. equestris populations was related to
      the similarity of vegetation, and whether there was more within-population
      genetic variation in habitats with a high number of plant species or in those
      with a large population of the primary food plant, Vincetoxicum hirundinaria. We
      also tested whether genetic differentiation of the populations was related to the
      geographic distance, and whether location of the populations on islands or on
      mainland, island size, or population size affected within-population genetic
      variation. Pairwise FST ranged from 0 to 0.1 indicating low to moderate genetic
      differentiation of populations. Differentiation increased with geographic
      distance between the populations, but was not related to the similarity of
      vegetation between the habitats. Genetic variation within the L. equestris
      populations did not increase with the population size of the primary food plant.
      However, the more diverse the plant community the higher was the level of genetic
      variation within the L. equestris population. Furthermore, the level of genetic
      variation did not vary significantly between island and mainland populations. The
      effect of the population size on within-population genetic variation was related
      to island size. Usually small populations are susceptible to loss of genetic
      variation, but small L. equestris populations on large islands seemed to maintain
      a relatively high level of within-population genetic variation. Our findings
      suggest that, in addition to geographic and species-specific ecological factors,
      the plant community affects population genetic structure of oligophagous
      herbivores. 

PMID- 24728343
TI  - High-resolution detection of recurrent aberrations in lung adenocarcinomas by
      array comparative genomic hybridization and expression analysis of selective
      genes by quantitative PCR.
AB  - Genomic abnormalities are the hallmark of cancers and may harbor potential
      candidate genes important for cancer development and progression. We performed
      array comparative genomic hybridization (array CGH) on 36 cases of primary lung
      adenocarcinoma (AD) using an array containing 2621 BAC or PAC clones spanning the
      genome at an average interval of 1 Mb. Array CGH identified the commonest
      aberrations consisting of DNA gains within 1p, 1q, 5p, 5q, 7p, 7q, 8q, 11q, 12p,
      13q, 16p, 17q, 20q, and losses with 6q, 9p, 10q and 18q. High-level copy gains
      involved mainly 7p21-p15 and 20q13.3. Dual color fluorescence in situ
      hybridization (FISH) was performed on a selective locus for validation of array
      CGH results. Genomic aberrations were compared with different clinicopathological
      features and a trend of higher number of aberrations in tumors with aggressive
      phenotypes and current tobacco exposure was identified. According to array CGH
      data, 23 candidate genes were selected for quantitative PCR (qPCR) analysis. The
      concordance observed between the genomic and expression changes in most of the
      genes suggested that they could be candidate cancer-related genes that
      contributed to the development of lung AD. 

PMID- 24728345
TI  - Community structure and the evolution of interdisciplinarity in Slovenia's
      scientific collaboration network.
AB  - Interaction among the scientific disciplines is of vital importance in modern
      science. Focusing on the case of Slovenia, we study the dynamics of
      interdisciplinary sciences from 1960 to 2010. Our approach relies on quantifying
      the interdisciplinarity of research communities detected in the coauthorship
      network of Slovenian scientists over time. Examining the evolution of the
      community structure, we find that the frequency of interdisciplinary research is
      only proportional with the overall growth of the network. Although marginal
      improvements in favor of interdisciplinarity are inferable during the 70s and
      80s, the overall trends during the past 20 years are constant and indicative of
      stalemate. We conclude that the flow of knowledge between different fields of
      research in Slovenia is in need of further stimulation.

PMID- 24728346
TI  - Supramolecular tailoring of protein-nanoparticle interactions using cucurbituril
      mediators.
AB  - Supramolecular modification of nanoparticle surfaces through threading of
      cucurbit[7]uril (CB[7]) onto surface ligands is used to regulate protein
      nanoparticle interactions. 

PMID- 24728347
TI  - Regulatory authorities and orthopaedic clinical trials on expanded mesenchymal
      stem cells.
AB  - Skeletal injuries requiring bone augmentation techniques are increasing in the
      context of avoiding or treating difficult cases with bone defects, bone healing
      problems, and bone regeneration limitations. Musculoskeletal severe trauma,
      osteoporosis-related fractures, and conditions where bone defect, bone collapse
      or insufficient bone regeneration occur are prone to disability and serious
      complications. Bone cell therapy has emerged as a promising technique to augment
      and promote bone regeneration. Interest in the orthopaedic community is
      considerable, although many aspects related to the research of this technique in
      specific indications may be insufficiently recognised by many orthopaedic
      surgeons. Clinical trials are the ultimate research in real patients that may
      confirm or refute the value of this new therapy. However, before launching the
      required trials in bone cell therapy towards bone regeneration, preclinical data
      is needed with the cell product to be implanted in patients to ensure safety and
      efficacy. These preclinical studies support the end-points that need to be
      evaluated in clinical trials. Orthopaedic surgeons are the ultimate players that,
      through their research, would confirm in clinical trials the benefit of bone cell
      therapies. To further foster this research, the pathway to eventually obtain
      authorisation from the National Competent Authorities and Research Ethics
      Committees under the European regulation is reviewed, and the experience of the
      REBORNE European project offers information and important clues about the current
      Voluntary Harmonization Procedure and other opportunities that need to be
      considered by surgeons and researchers on the topic. 

PMID- 24728348
TI  - Comparison of the efficacy of a distal clavicular locking plate versus a
      clavicular hook plate in the treatment of unstable distal clavicle fractures and
      a systematic literature review.
AB  - PURPOSE: The purpose of this study was to retrospectively compare and review the
      clinical outcomes between the distal clavicular locking plate and clavicular hook
      plates in the treatment of unstable distal clavicle fractures; moreover, the
      relevant literature of the two fixation methods was reviewed systematically to
      identify the non-union, complications, or functional scores, according to the
      treatment methods and determine which treatment method is better. METHODS: Sixty
      six patients with 66 unstable distal clavicle fractures who underwent open
      reduction and internal fixation with either a distal clavicular locking plate (36
      patients) or a clavicular hook plate (30 patients ) were evaluated. The main
      outcome comparisons included Constant score, rate of non-union, rate of
      complication, and rate of returning to work three months postoperatively.
      RESULTS: No significant difference was found between locking plate and hook plate
      groups in union rate and Constant score (P > 0.05). However, the results
      indicated that the distal clavicular locking plate group had a significantly
      lower rate of complications (P < 0.05) and symptomatic hardware (P < 0.05). In
      addition, the distal clavicular locking plate facilitated the return to work
      better than the clavicular hook plate (P < 0.05). CONCLUSIONS: Both distal
      clavicular locking plate and clavicular hook plate achieved good results in the
      treatment of unstable distal clavicle fractures; however, internal fixation with
      a distal clavicular locking plate had greater ability to return to their previous
      work after surgery in three months and fewer complications than the clavicular
      hook plate.

PMID- 24728349
TI  - Pediatric anemia in rural Ghana: a cross-sectional study of prevalence and risk
      factors.
AB  - OBJECTIVE: To assess anemia prevalence and identify associated parameters in
      children <3 years of age in a rural area of Ghana. METHOD: Univariate and
      multivariate logistic regression of cross-sectional survey results from 861
      children aged <3 years attending routine immunization services in Berekum
      district. RESULTS: Anemia prevalence was 73.1%; most were either mildly (31.2%)
      or moderately (38.7%) affected. Risk factors for anemia (hemoglobin < 11.0 g/dl)
      in multivariate analysis were malaria parasitemia and male sex; these factors and
      younger age were associated with anemia severity. A partial defect in glucose-6
      phosphate dehydrogenase was associated with decreased severity. Height-for-age,
      but not weight-for-age, was associated with anemia and its severity. CONCLUSIONS:
      Malaria parasitemia was strongly associated with anemia and its severity,
      suggesting that malaria control may be the most effective way to reduce the
      burden of anemia in rural Ghanaian children.

PMID- 24728350
TI  - Mechanosensitive physiology of Chlamydomonas reinhardtii under direct membrane
      distortion.
AB  - Cellular membrane distortion invokes variations in cellular physiology. However,
      lack of an appropriate system to control the stress and facilitate molecular
      analyses has hampered progress of relevant studies. In this study, a microfluidic
      system that finely manipulates membrane distortion of Chlamydomonas reinhardtii
      (C. reinhardtii) was developed. The device facilitated a first-time demonstration
      that directs membrane distortion invokes variations in deflagellation, cell
      cycle, and lipid metabolism. C. reinhardtii showed a prolonged G1 phase with an
      extended total cell cycle time, and upregulated Mat3 regulated a cell size and
      cell cycle. Additionally, increased TAG compensated for the loss of cell mass.
      Overall, this study suggest that cell biology that requires direct membrane
      distortion can be realized using this system, and the implication of cell cycle
      with Mat3 expression of C. reinhardtii was first demonstrated. Finally, membrane
      distortion can be an attractive inducer for biodiesel production since it is
      reliable and robust. 

PMID- 24728351
TI  - Inflammation-induced repression of chromatin bound by the transcription factor
      Foxp3 in regulatory T cells.
AB  - The transcription factor Foxp3 is indispensable for the ability of regulatory T
      cells (Treg cells) to suppress fatal inflammation. Here we characterized the role
      of Foxp3 in chromatin remodeling and the regulation of gene expression in
      actively suppressive Treg cells in an inflammatory setting. Although genome-wide
      occupancy of regulatory elements in DNA by Foxp3 was similar in resting Treg
      cells and those activated in vivo, Foxp3-bound enhancer elements in the DNA were
      poised for repression only in activated Treg cells. Following activation, Foxp3
      bound sites showed diminished accessibility of chromatin and selective deposition
      of histone H3 trimethylated at Lys27 (H3K27me3), which was associated with
      recruitment of the histone methyltransferase Ezh2 and downregulation of the
      expression of nearby genes. Thus, Foxp3 poises its targets for repression by
      facilitating the formation of repressive chromatin in Treg cells upon their
      activation in response to inflammatory cues. 

PMID- 24728352
TI  - A regulatory role for TGF-beta signaling in the establishment and function of the
      thymic medulla.
AB  - Medullary thymic epithelial cells (mTECs) are critical in establishing and
      maintaining the appropriate microenvironment for negative selection and
      maturation of immunocompetent T cells with a self-tolerant T cell antigen
      receptor repertoire. Cues that direct proliferation and maturation of mTECs are
      provided by members of the tumor necrosis factor (TNF) superfamily expressed on
      developing thymocytes. Here we demonstrate a negative role of the morphogen TGF
      beta in tempering these signals under physiological conditions, limiting both
      growth and function of the thymic medulla. Eliminating TGF-beta signaling
      specifically in TECs or by pharmacological means increased the size of the mTEC
      compartment, enhanced negative selection and functional maturation of medullary
      thymocytes as well as the production of regulatory T cells, thus reducing the
      autoreactive potential of peripheral T cells. 

PMID- 24728354
TI  - Studies on coccidian oocysts (Apicomplexa: Eucoccidiorida).
AB  - The oocysts of the coccidia are robust structures, frequently isolated from the
      feces or urine of their hosts, which provide resistance to mechanical damage and
      allow the parasites to survive and remain infective for prolonged periods. The
      diagnosis of coccidiosis, species description and systematics, are all dependent
      upon characterization of the oocyst. Therefore, this review aimed to the provide
      a critical overview of the methodologies, advantages and limitations of the
      currently available morphological, morphometrical and molecular biology based
      approaches that may be utilized for characterization of these important
      structures. It has become apparent that no single methodology is sufficient to
      fully characterize these structures and the majority of researchers favor the use
      of combinational or polyphasic approaches. 

PMID- 24728353
TI  - Striatal synaptic dysfunction and hippocampal plasticity deficits in the Hu97/18
      mouse model of Huntington disease.
AB  - Huntington disease (HD) is a fatal neurodegenerative disorder caused by a CAG
      repeat expansion in the gene (HTT) encoding the huntingtin protein (HTT). This
      mutation leads to multiple cellular and synaptic alterations that are mimicked in
      many current HD animal models. However, the most commonly used, well
      characterized HD models do not accurately reproduce the genetics of human
      disease. Recently, a new 'humanized' mouse model, termed Hu97/18, has been
      developed that genetically recapitulates human HD, including two human HTT
      alleles, no mouse Hdh alleles and heterozygosity of the HD mutation. Previously,
      behavioral and neuropathological testing in Hu97/18 mice revealed many features
      of HD, yet no electrophysiological measures were employed to investigate possible
      synaptic alterations. Here, we describe electrophysiological changes in the
      striatum and hippocampus of the Hu97/18 mice. At 9 months of age, a stage when
      cognitive deficits are fully developed and motor dysfunction is also evident,
      Hu97/18 striatal spiny projection neurons (SPNs) exhibited small changes in
      membrane properties and lower amplitude and frequency of spontaneous excitatory
      postsynaptic currents (sEPSCs); however, release probability from presynaptic
      terminals was unaltered. Strikingly, these mice also exhibited a profound
      deficiency in long-term potentiation (LTP) at CA3-to-CA1 synapses. In contrast,
      at 6 months of age we found only subtle alterations in SPN synaptic transmission,
      while 3-month old animals did not display any electrophysiologically detectable
      changes in the striatum and CA1 LTP was intact. Together, these data reveal
      robust, progressive deficits in synaptic function and plasticity in Hu97/18 mice,
      consistent with previously reported behavioral abnormalities, and suggest an
      optimal age (9 months) for future electrophysiological assessment in preclinical
      studies of HD. 

PMID- 24728356
TI  - Molecular and serological detection of Ehrlichia canis in naturally exposed dogs
      in Iran: an analysis on associated risk factors.
AB  - The general aim of this study, which was conducted for the first time in Iran,
      was to evaluate the seroprevalence and geographical distribution of Ehrlichia
      canis in a dog population in Iran, followed by molecular confirmation using PCR
      and sequencing. Blood samples were collected from 240 dogs in different areas of
      Alborz and Tehran Provinces and initially analyzed using the immunofluorescent
      antibody (IFA) test to detect anti-Ehrlichia canis IgG antibodies. Subsequently,
      nested PCR was performed based on a fragment of the 16S rRNA gene of E. canis on
      serologically positive samples. The results showed that 40/240 dogs (16.6%)
      presented anti-Ehrlichia canis IgG antibodies and that nine of the blood samples
      from the 40 seropositive dogs (22.5%) contained E. canis DNA, which was confirmed
      by sequencing. The seroprevalence of E. canis tended to be higher in purebred,
      one to three-year-old male dogs living in the Plain zone, in rural areas;
      however, this difference was not statistically significant. 

PMID- 24728357
TI  - Distribution of bovine fasciolosis and associated factors in south Espirito
      Santo, Brazil: an update.
AB  - The geographical distribution and factors associated with bovine fasciolosis in
      the south of Espirito Santo were updated and the prevalences of this disease and
      of snails of the genus Lymnaea in the municipality of Jeronimo Monteiro were
      calculated. In the first stage, fecal samples were collected from 10% of the
      herds of 115 farms in 23 municipalities and interviews were conducted with
      owners. Generalized linear mixed models were used. In the second stage, in
      Jeronimo Monteiro municipality, feces and mollusks were collected from all farms
      registered in the milk cooperatives in the region. The mollusks were identified
      and examined for infection by Fasciola hepatica. Fasciolosis was diagnosed in 18
      (78%) of the 23 municipalities. Of the 1157 fecal samples examined, 19.01% were
      positive for eggs of F. hepatica. The final model shows statistical evidence of
      associations between positive farms and previous cases of fasciolosis and
      concomitant grazing of cattle with other definitive hosts. In the evaluated farms
      from the studied municipality the prevalence of fasciolosis and Lymnaea was of
      66.7% and 23.8%, respectively. Mollusks were found in flooded areas and the
      animals' drinking water troughs. The wide geographical distribution of bovine
      fasciolosis in the south of Espirito Santo requires control measures to prevent
      its expansion towards the north of this state and other places characterized as
      F. hepatica free-infection. 

PMID- 24728358
TI  - Morphological changes and parasite load of the adrenal from dogs with visceral
      leishmaniasis.
AB  - The objective of this study was to analyze morphological changes and parasite
      loads in the adrenal gland from 45 dogs with visceral leishmaniasis (VL). The
      animals were from the Zoonosis Control Center of Aracatuba, state of Sao Paulo,
      which is an endemic region for the disease. These animals were euthanized due to
      positive diagnoses of VL. The dogs were classified into asymptomatic,
      oligosymptomatic and symptomatic groups. The parasite load was determined by
      immunohistochemistry, using VL-positive dog hyperimmune serum. Nine dogs showed
      an inflammatory infiltrate composed, predominantly, of plasma cells and
      macrophages. However, only eight dogs showed macrophages with amastigote forms of
      the parasite, immunolabeled in the cytoplasm. The medullary and reticular layers
      were the most affected areas, possibly due to a favorable microenvironment
      created by hormones in these regions. The density of parasites in the glandular
      tissue was not associated with clinical signs of VL (P > 0.05). However, the
      presence of the parasite was always associated with the presence of a
      granulomatous inflammatory infiltrate. This gland may not be an ideal place for
      the parasite's multiplication, but the presence of injuries to the glandular
      tissue could influence the dog's immune system, thus favoring the parasite's
      survival in the host's different organs. 

PMID- 24728359
TI  - Comparison of an ELISA assay for the detection of adhesive/invasive Neospora
      caninum tachyzoites.
AB  - Neospora caninum belongs to the phylum Apicomplexa, the causative agent of
      neosporosis, which leads to economic impacts on cattle production. A common
      feature among apicomplexan parasites is the invasive process driven mostly by the
      parasite. As a first evaluation of candidate molecules that play a possible role
      by interfering in this invasive process, the in vitro invasion assay is a fast
      and direct way to screen future agonists or antagonists. This work involved the
      development of a new cell culture ELISA and transient beta-galactosidase activity
      applied to the semi-quantitative detection of N. caninum in Vero cell culture.
      Cell culture ELISA is based on histochemistry and immunology, resulting in a
      colorimetric reaction. The beta-galactosidase activity was obtained by the
      transient transfection of the lacZ gene under control of RPS13 promoter of N.
      caninum. These methods were used to evaluate the effects of temperature (37
      degrees C and 85 degrees C) on the invasion and adhesion of tachyzoites. The
      three tested methods (real time PCR, beta-galactosidase activity and ELISA)
      showed a similar pattern, indicating that different methods may be complementary.

PMID- 24728360
TI  - Parasites of native Cichlidae populations and invasive Oreochromis niloticus
      (Linnaeus, 1758) in tributary of Amazonas River (Brazil).
AB  - This study provides the first investigation on acquisition of parasites in
      invasive O. niloticus by parasite species of native Cichlidae from the Igarape
      Fortaleza basin, Northern Brazil. There were examined 576 specimens of 16 species
      of native cichlids and invasive O. niloticus collected in the main channel and
      the floodplain area of this tributary of Amazon River. The invasive O. niloticus
      was poorly parasitized having only Ichthyophthirius multifiliis, Trichodina
      centrostrigeata, Paratrichodina africana, Trichodina nobilis (Protozoa) and
      Cichlidogyrus tilapiae (Monogenoidea), and this host has not acquired any
      parasite species common to the native ichthyofauna region. In contrast, species
      of native cichlids showed rich fauna of parasites with predominance of
      Monogenoidea species, larvae and adults of Nematoda, Digenea, Cestoidea and
      Acanthocephala, besides four species of Protozoa and four Crustacea. However,
      only T. nobilis was acquired by native fish, the Aequidens tetramerus, which is a
      new host for this exotic Trichodinidae. In O. niloticus, well established in the
      region, the small number of helminth species may be associated with its
      rusticity, good adaptation in the new environment and also the presence of native
      parasites with relative specificity, but without ability to complete its life
      cycle in this invasive host of this ecosystem. 

PMID- 24728361
TI  - Epidemiological survey of Lutzomyia longipalpis infected by Leishmania infantum
      in an endemic area of Brazil.
AB  - The objective of this study was to perform an epidemiological survey to determine
      the areas at risk of visceral leishmaniasis through the detection and
      quantification of natural infection by Leishmania infantum in Lutzomyia
      longipalpis. The sandflies were captured between February 2009 and January 2010,
      at 21 sites in four regions of the Fortaleza municipality. Samples were screened
      for the presence of Leishmania DNA by Real Time PCR (qPCR), amplification of kDNA
      minicircle sequence. Out of the 123 pools of analyzed sandflies, 45 were positive
      for L.infantum, and the minimum infection rate was 3.7%. In the north, south,
      east and west regions, the pool screen assay predicted sand-fly infection
      prevalence of 3.4%, 4.7%, 4.9% and 8.4%, respectively. The parasite load ranged
      from 2.45 +/- 0.96 to 2,820,246 +/- 106,072. No statistical differences were
      found with respect to the frequency of sand-fly infection between the regions
      (P=0.3014), seasons (P = 0.3906) or trap locations (P = 0.8486). Statistical
      differences were found with respect to the frequency of sand-fly infection
      between the two seasons only in the west region (P=0.0152). The qPCR was able to
      detect and quantify L. infantum in L. longipalpis, therefore succeeding in
      identifying the areas of greatest risk of VL transmission. 

PMID- 24728362
TI  - Epidemiological aspects of visceral leishmaniasis in Jaciara, Mato Grosso,
      Brazil, 2003 to 2012.
AB  - Visceral leishmaniasis (VL) is caused by Leishmania (L.) infantum chagasi in the
      Americas. In Brazil, it is transmitted by sandflies of the species Lutzomyia
      longipalpis and L. cruzi, and dogs are the main domestic reservoirs. The aim of
      this study was to analyze data relating to VL transmission in Jaciara, state of
      Mato Grosso, and discuss vector distribution, domestic reservoirs, and human
      cases that occurred between 2003 and 2012. The data for analysis were obtained
      from the Notifiable Diseases Information System (human), the State Health
      Department's Environmental Monitoring Agency (canine data) and the State Health
      Department's Entomology Laboratory (sandfly data). Over this period, Jaciara had
      19 autochthonous human cases (12 males and seven females), with one death 2,273.
      Out of the 7,545 dogs tested by enzyme immunoassay and indirect
      immunofluorescence were positive. The sandflies collected comprised 5,015
      individuals belonging to 24 species, with a predominance of L. whitmani followed
      by L. cruzi. The results showed that the parasite has frequent circulation and
      that the vector L. cruzi is widely distributed over all months, thus suggesting
      that transmission may occur at any time of the year. 

PMID- 24728363
TI  - Geohelminth contamination of public areas and epidemiological risk factors in
      Curitiba, Brazil.
AB  - This study aimed to investigate the frequency of geohelminthic contamination of
      public parks and squares in Curitiba, state of Parana, Brazil, between August and
      December 2010. A total of 345 samples were collected from 69 sandboxes in
      different areas and were tested using the Faust, Lutz and Baermann
      parasitological techniques. Potential risk factors associated with soil
      contamination were also analyzed. A total of 36% of the samples (124/345) were
      positive for helminths and 65.2% of the areas (45/69) were classified as
      contaminated in one or more samples. The most commonly identified parasite eggs
      were Ancylostoma sp. (14.5%; 50/345); followed by Toxocara sp. (9.6%; 33/345) and
      the Strongyloidea superfamily (excluding hookworms) (2.3%; 8/345). The analysis
      on the epidemiological risk factors indicated that the presence of dogs and feces
      in the sandboxes increased the chances of contamination of the site. Use of
      fences had a protective positive impact that reduced soil contamination. Health
      education programs should be applied within the community to minimize the risk of
      human contact with dogs' feces. Use of fencing in these areas is highly
      recommended to prevent or reduce the users' contact with animal excrement. 

PMID- 24728364
TI  - Molecular and morphological characterization of Contracaecum pelagicum (Nematoda)
      parasitizing Spheniscus magellanicus (Chordata) from Brazilian waters.
AB  - Three new sequences of Mitochondrial cytochrome c-oxidase subunit 2 (mtDNA cox-2)
      from C. pelagicum parasite of Spheniscus magellanicus, the Magelanicus penguin,
      were determined from Brazilian waters. The sequences presented 99 and 98% of
      similarity with C. pelagicum sequences from Argentina, deposited on GenBank for
      the same genetic region and with a strong statistical support inferred from the
      phylogenetic tree. The morphological and ultrastructural studies that were
      carried out confirmed the genetic analysis. 

PMID- 24728365
TI  - Nematode infection among ruminants in monsoon climate (Ban-Lahanam, Lao PDR) and
      its role as food-borne zoonosis.
AB  - Trichostrongylids infection has gained significant public health importance since
      Trichostrongylus spp. infections have been reported in humans in Lao PDR. In this
      study, gastrointestinal nematodes were identified and the intensity of infections
      was determined in goats and cattle, which are animals greatly used for meat
      production in Lahanam Village, Lao PDR. The total number of goats and bovines was
      23 and 29, respectively, pertaining to 32 households surveyed in the area. Feacal
      samples were randomly collected from 14 goats and 11 bovines. Ninety three
      percent (13/14) of goats and 36% (3/11) of cattle were infected, with an average
      of 1,728 and 86 eggs per gram of faeces (EPG), respectively. Coproculture showed
      Trichostrongylus spp. (goats 16%; bovines 48%), Haemonchus spp. (goats 69%;
      bovines 37%), Cooperia spp. (bovines 8%) and Oesophagostomum spp. (goats 15%;
      bovines 6%). After performing the necropsy on an adult goat, Trichuris spp. was
      also found. We confirmed the presence of Oesophagostomum spp., H. contortus and
      T. colubriformis by morphology and DNA sequencing analysis of the ITS region of
      rDNA. Due to interactions between humans and goats in Lahanam Village and high
      EPG results, the diagnosis of species and the intensity of gastrointestinal
      nematode infection in these animals are important public-health issues. Other
      ruminant parasites, such as Oesophagostomum and Haemonchus, found in caprines and
      bovines, are reported to be causes of zoonosis and their presence in humans
      should be investigated in future field surveys in this area. 

PMID- 24728366
TI  - Seroprevalence rates of antibodies against Theileria equi in team roping horses
      from central-western region of Parana.
AB  - The purpose of this study was to estimate the prevalence of Theileria equi in
      horses from central western region of Parana state, Brazil. The presence of
      antibodies IgG against T. equi was determined in serum samples obtained from 400
      team roping horses of the district of Guarapuava by the enzyme-linked
      immunosorbent assay (ELISA). Results showed that 242 (61%) animals were positive
      which demonstrates that equine piroplasmosis is widespread and therefore it might
      be a contributing factor for the irregular performance among athletes horses in
      the region studied. No association regarding age and sex were observed (p>0.05).
      To our knowledge, this is the first report describing a serological survey on
      equine piroplasmosis in the state of Parana, Brazil. 

PMID- 24728367
TI  - Seroprevalence of Toxoplasma gondii in cats (Felis catus, Linnaeus 1758) living
      in Lima, Peru.
AB  - The aim of this study was to determine the frequency of infection by T. gondii in
      cats, by examining serum and fecal samples from animals attended at veterinary
      clinics in the Metropolitan Region of Lima, Peru. We collected and analyzed 154
      cat serum samples and 50 fecal samples, regardless of the age, gender or breed.
      In parallel with the sample collections, the owners answered an epidemiological
      questionnaire that investigated the following variables: age group, gender,
      lifestyle (confined, semi-confined or free-living animals), feeding and hunting
      habits. The serum and fecal samples were analyzed using indirect hemagglutination
      (IHA) and coproparasitological tests, respectively. IHA showed that the frequency
      of cat exposure to T. gondii was 11%. Age and gender showed no association with
      exposure to the parasite. Exposure among the cats was associated with hunting (x2
      = 4.98, p = 0.016) and feeding habits (x2 = 13.34, p = 0.001): those fed with raw
      meat were more exposed than those fed with commercial cat food (x2 = 9.50, p =
      0.004) or with homemade food (x2 = 4.1, p = 0.027). The frequency of cats
      diagnosed in the chronic phase of T. gondii infection was 88% (15/17). No T.
      gondii oocysts were found in any of the 50 fecal samples examined. 

PMID- 24728368
TI  - Longevity and viability of Taenia solium eggs in the digestive system of the
      beetle Ammophorus rubripes.
AB  - The present study evaluated the capacity of Ammophorus rubripes beetles to carry
      Taenia solium eggs, in terms of duration and viability of eggs in their digestive
      system. One hundred beetles were distributed into five polyethylene boxes, and
      then they were infected with T. solium eggs. Gravid proglottids of T. solium were
      crushed and then mixed with cattle feces. One gram of this mixture was placed in
      each box for 24 hours, after which each group of beetles was transferred into a
      new clean box. Then, five beetles were dissected every three days. Time was
      strongly associated with viability (r=0.89; P<0.001) and the calculated time to
      cero viability is 36 days. The eggs in the intestinal system of each beetle were
      counted and tested for viability. Taenia solium eggs were present in the beetle's
      digestive system for up to 39 days (13th sampling day out of 20), gradually
      reducing in numbers and viability, which was 0 on day 36 post-infection. Egg
      viability was around 40% up to day 24 post-infection, with a median number of
      eggs of 11 per beetle at this time. Dung beetles may potentially contribute
      towards dispersing T. solium eggs in endemic areas. 

PMID- 24728369
TI  - Seroprevalence and risk factors for Toxoplasma gondii infection in pigs in
      southern Piaui.
AB  - This study is aimed to assess the prevalence and risk factors associated with T.
      gondii infection in pigs. We evaluated 143 pigs, in 10 randomly-chosen farms
      located in Southern Piaui. The pig's blood serum was analyzed through ELISA in
      detection of anti-T. gondii antibodies. A seroprevalence of 25.5% was observed in
      the pigs that reacted against T. gondii antigens. The data from the records
      demonstrated an association with some factors such as: age, diet, type of
      management, breed and presence of cats in the farms with a prevalence of T.
      gondii. With the exception of sex, all others features represent risk factors for
      T. gondii infection. Furthermore, our data contributed to the understanding of
      the T. gondii seroprevalence in pig farms located in Southern Piaui. 

PMID- 24728370
TI  - Occurrence of gastrointestinal parasites in goats from the Western Santa
      Catarina, Brazil.
AB  - This study aims to investigate the occurrence of gastrointestinal parasites in
      goats from the Western Santa Catarina, Brazil. Twenty four farms were analyzed in
      17 different municipalities. Animals (n=217) from different production purposes
      (milk and meat) and age were randomly chosen. Fecal samples were collected from
      the rectum stored in plastic bottles and transported to the laboratory in
      portable coolers at 10  degrees C. The technique of centrifugal flotation with
      saturated sugar solution was carried out in order to investigate the presence of
      eggs, cysts, and oocysts of gastrointestinal parasites. In 88.9% of the
      investigated animals, it was observed that the presence of nematode eggs which
      belongs to the Strongylida order, after cultivation and larvae identification
      were identified as Haemonchus spp., Trichostrongylus spp., Teladorsagia spp.,
      Cooperia spp., and Oesophagostomum spp. Eggs of Thysanosoma, Trichuris, Moniezia,
      and Neoascaris genus were also observed. Additionally, the presence of oocysts of
      Eimeria spp. and Cryptosporidium spp. as well as cysts of Giardia spp., and
      Entamoeba spp. were verified. In all the farms evaluated, the animals showed a
      single or mixed infection, with the highest occurrence of helminths belonging to
      the Haemonchus and Trichostrongylus genus, as well as the protozoan Eimeria. 

PMID- 24728371
TI  - Optimization of a molecular method for the diagnosis of canine babesiosis.
AB  - Babesiosis is a hemolytic disease caused by protozoans of the genus Babesia
      (Apicomplexa). This disease occurs worldwide and is transmitted by ticks to a
      variety of mammals, including humans. The objective of the present study was to
      optimize a molecular approach for the detection of a fragment of 18S rDNA of
      Babesia canis, Babesia vogeli, Babesia rossi or Babesia gibsoni based on a single
      semi-nested Polymerase Chain Reaction (PCR), and compare the efficiency of this
      approach with that of a simple PCR protocol. To this end, 100 blood samples
      collected from dogs with suspected hemoparasite infections were analyzed. A
      comparison of the results of simple PCR and semi-nested PCR indicated a highly
      significant difference (p value = 0.0000). While only five (5%) of the samples
      tested positive using the simple protocol, 22 (22%) were positive using the snPCR
      technique. The results of this study reinforce the findings of previous studies,
      which have demonstrated the greater sensitivity of tests based on nested or semi
      nested PCR. Therefore, to avoid false-negative results due to low levels of
      parasitemia, we suggest the preferential use of this protocol in epidemiological
      studies of canine babesiosis, particularly those that require reliable estimates
      of the prevalence of infection. 

PMID- 24728372
TI  - Dioctophyme renale Goeze, 1782 in a cat with a supernumerary kidney.
AB  - This study reports a case of parasitism by Dioctophyme renale in a supernumerary
      kidney and abdominal cavity of a female cat in Brazil. The three-year-old cat of
      indeterminate breed presented abdominal distension and was taken to the
      University of Contestado Veterinary Hospital in Canoinhas, state of Santa
      Catarina, since the owner suspected pregnancy. An ultrasound scan did not confirm
      pregnancy but revealed parasitism in the kidney. This case is worth reporting
      because domestic cats are rarely hosts of this nematode species. 

PMID- 24728373
TI  - Deep-sequencing method for quantifying background abundances of symbiodinium
      types: exploring the rare symbiodinium biosphere in reef-building corals.
AB  - The capacity of reef-building corals to associate with environmentally
      appropriate types of endosymbionts from the dinoflagellate genus Symbiodinium
      contributes significantly to their success at local scales. Additionally, some
      corals are able to acclimatize to environmental perturbations by shuffling the
      relative proportions of different Symbiodinium types hosted. Understanding the
      dynamics of these symbioses requires a sensitive and quantitative method of
      Symbiodinium genotyping. Electrophoresis methods, still widely utilized for this
      purpose, are predominantly qualitative and cannot guarantee detection of a
      background type below 10% of the total Symbiodinium population. Here, the
      relative abundances of four Symbiodinium types (A13, C1, C3, and D1) in mixed
      samples of known composition were quantified using deep sequencing of the
      internal transcribed spacer of the ribosomal RNA gene (ITS-2) by means of Next
      Generation Sequencing (NGS) using Roche 454. In samples dominated by each of the
      four Symbiodinium types tested, background levels of the other three types were
      detected when present at 5%, 1%, and 0.1% levels, and their relative abundances
      were quantified with high (A13, C1, D1) to variable (C3) accuracy. The potential
      of this deep sequencing method for resolving fine-scale genetic diversity within
      a symbiont type was further demonstrated in a natural symbiosis using ITS-1, and
      uncovered reef-specific differences in the composition of Symbiodinium
      microadriaticum in two species of acroporid corals (Acropora digitifera and A.
      hyacinthus) from Palau. The ability of deep sequencing of the ITS locus (1 and 2)
      to detect and quantify low-abundant Symbiodinium types, as well as finer-scale
      diversity below the type level, will enable more robust quantification of local
      genetic diversity in Symbiodinium populations. This method will help to elucidate
      the role that background types have in maximizing coral fitness across diverse
      environments and in response to environmental change. 

PMID- 24728374
TI  - The relationship between serum insulin-like growth factor I levels and ischemic
      stroke risk.
AB  - OBJECTIVE: The aim of the study was to assess the relationship between insulin
      like growth factor I (IGF-I) serum levels and acute ischemic stroke (AIS) in a
      Chinese population. METHODS: All consecutive patients with first-ever AIS from
      August 1, 2011 to July 31, 2013 were recruited to participate in the study. The
      control group comprised 200 subjects matched for age, gender, and conventional
      vascular risk factors. IGF-I serum levels were determined by chemiluminescence
      immunoassay. The National Institutes of Health Stroke Scale (NIHSS) score was
      assessed on admission blinded to serum IGF-I levels. RESULTS: The median serum
      IGF-1 levels were significantly (P = 0.011) lower in AIS patients (129; IQR, 109
      153 ng/mL) compared with control cases (140; IQR, 125-159 ng/mL). We found that
      an increased risk of AIS was associated with IGF-I levels <=135 ng/mL (unadjusted
      OR: 4.17; 95% CI: 2.52-6.89; P = 0.000). This relationship was confirmed in the
      dose-response model. In multivariate analysis, there was still an increased risk
      of AIS associated with IGF-I levels <=135 ng/mL (OR: 2.16; 95% CI:1.33-3.52; P =
      0.002) after adjusting for possible confounders. CONCLUSION: Lower IGF-I levels
      are significantly related to risk of stroke, independent from other traditional
      and emerging risk factors, suggesting that they may play a role in the
      pathogenesis of AIS. Thus, strokes were more likely to occur in patients with low
      serum IGF-I levels in the Chinese population; further, post-ischemic IGF-I
      therapy may be beneficial for stroke.

PMID- 24728375
TI  - Inverse solvent effects in the heterogeneous and homogeneous epoxidation of cis-2
      heptene with [2-percarboxyethyl]-functionalized silica and meta-chloroperbenzoic
      acid.
AB  - The rate constants for the epoxidation of cis-2-heptene with [2-percarboxyethyl]
      functionalized silica (1a) and meta-chloroperbenzoic acid (mCPBA) (1b) in
      different solvents have been determined at temperatures in the -10 to 40  degrees
      C range. The heterogeneous epoxidation exhibits a dependence of the reaction rate
      on solvent polarity opposite to its homogeneous counterpart and anomalous
      activation parameters in n-hexane, which are interpreted in terms of the surface
      promoted solvent structure at the solid-liquid interface. The results show that
      highly polar solvents can strongly inhibit heterogeneous reactions performed with
      silica-supported reagents or catalysts. 

PMID- 24728376
TI  - Primitive reflexes in amyotrophic lateral sclerosis: prevalence and correlates.
AB  - Identifying frontal impairment in ALS is an important goal albeit disease
      dedicated tools are still scarce. For this reason, we decided to consider
      primitive reflexes (PRs), variably regarded as correlates of frontal release
      and/or of upper motor neuron (UMN) impairment, often in the setting of dementias.
      Specifically, the aims of this work consisted in assessing the exact prevalence
      of the combination of seven PRs in ALS, trying to clarify their role as putative
      proxies of cognitive impairment or of UMN dysfunction. In this cross-sectional
      study, 50 consecutive ALS outpatients were evaluated for the presence of:
      palmomental (PM), corneomandibular (CM), glabella tap (MY), rooting, sucking,
      snout, and grasping reflexes. Cognitive screening was performed by the Frontal
      Assessment Battery (FAB) and the Weigl's Sorting test (WST); UMN dysfunction was
      concomitantly evaluated. PM, CM and MY were more frequently detected (62, 52, and
      44 % of the ALS sample, respectively), while the other reflexes were under
      represented. Patients displaying three or more PRs had significantly lower FAB
      and WST scores. On the other hand, UMN dysfunction was only moderately associated
      to PRs. In conclusion, PRs' assessment is a promising complementary tool for
      screening cognitive impairment in ALS; however, further work will be necessary to
      establish its added value with respect to already existing ALS-dedicated
      screening tools for cognition.

PMID- 24728378
TI  - [Swallowing examination for ENT specialists].
AB  - Dysphagias, together with the diseases resulting therefrom, severely reduce
      patients' quality of life and substantially increase the costs of public health,
      making efficient therapy a prime concern. Among pathophysiologically oriented
      diagnostic procedures, the endoscopic examination of swallowing has emerged
      within the past 20 years as an indispensable standard examination with high
      sensitivity and specificity. Thus, every ears, nose, and throat (ENT) physician
      and phoniatric specialist should be familiar with this procedure, in order to
      ensure widest possible access to it, not only in hospitals but also in outpatient
      settings and in healthcare establishments. In this article, the preconditions,
      execution, and evaluation of the endoscopic examination are described and its
      relevance for immediate or long-term therapeutic treatment is discussed. 

PMID- 24728377
TI  - A meta-analysis of the diagnostic accuracy of two commercial NS1 antigen ELISA
      tests for early dengue virus detection.
AB  - BACKGROUND: Dengue virus (DENV) NS1 antigen detection is regarded as an early
      diagnostic marker. Accordingly, several studies have evaluated the performance of
      tests that utilize NS1 capture, but the results of individual studies may be
      limited due to the restricted sample size of the patients recruited. Therefore,
      our objective was to perform a meta-analysis of the diagnostic accuracy of two
      commercial NS1 ELISAs (Panbio and Platelia). METHODS AND RESULTS: Studies of
      interest were found in PubMed, Embase and Google Scholar databases using defined
      inclusion/exclusion criteria. A total of 30 studies containing 12,105 total
      enrolled patients were included. The results were as follows: 1) Panbio assays
      showed low overall performance, sensitivity 66% (95% confidence interval (CI) 61
      71), specificity 99% (95% CI 96-100), positive likelihood ratio (LR+) 98 (95% CI
      20-464), negative likelihood ratio (LR-) 0.3 (95% CI 0.2-0.4), diagnostic odds
      ratio (DOR) 289 (95% CI 59-1412); 2) Platelia assays showed high overall
      performance, sensitivity 74% (95% CI 63-82), specificity 99% (95% CI 97-100), LR+
      175 (95% CI 28-1099), LR- 0.3 (95% CI 0.2-0.4), DOR 663 (95% CI 98-4478). The
      lowest sensitivity values were for secondary infections (57% [95% CI 47-67] and
      66% [95% CI 53-77] for Panbio and Platelia, respectively) and for the detection
      of DENV4. Regarding clinical manifestations, the sensitivity of Platelia was 69%
      (95% CI 43-86) and 60% (95% CI 48-70) for fever and dengue hemorrhagic fever,
      respectively. In addition, the sensitivity of both tests was slightly lower for
      samples from Southeast Asia and Oceania. CONCLUSION: DENV1 samples gave higher
      sensitivity results for both tests. We observed that factors negatively
      influencing the tests, such as the type of infection, geographical origins of
      samples and viral serotypes, require further investigation to optimize the
      diagnostic accuracy.

PMID- 24728379
TI  - Electrocatalysis on gold.
AB  - This perspective article reviews recent advances in the study of important
      catalytic reactions on gold electrodes. The paper discusses both oxidation and
      reduction reactions: the oxidation of carbon monoxide and alcohols as well as the
      oxygen reduction reaction on gold electrodes and also a brief discussion of other
      interesting reactions on gold electrodes such as the amine borane oxidation and
      the CO2 reduction. A common theme in electrocatalysis on gold is the sensitive
      dependence of various reaction rates on pH and gold surface structure. The
      electrocatalysis of redox reactions on gold is highly pH dependent, often
      preferring alkaline media, due to the prominent role of negatively charged
      reaction intermediates related to the fact that gold does not bind the neutral
      intermediates strongly enough. Gold also tends to be a selective catalyst, again
      due to its weak adsorption properties, as on gold the reaction often stops when a
      difficult bond breaking or making event will be the necessary next step. 

PMID- 24728380
TI  - Response differences of intersegmental auditory neurons recorded close to or far
      away from the presumed spike-generating zone.
AB  - Intracellular recordings may give valuable information about processing of a
      neuron and possibly its input from the network. Impalement with an electrode
      causes injury to the cell and depolarization from intrusion of extracellular
      fluid. Thus, penetration artefacts may contaminate recordings and conceal or even
      alter relevant information. These penetration artefacts may have the strongest
      impact close to the spike-generating zone near the dendrites. Recordings in
      axonal portions might therefore be less vulnerable while providing insufficient
      information about the synaptic input. In this study, we present data of five
      previously identified intersegmental auditory neurons of a bushcricket
      independently recorded in their dendrites (prothorax) and axon (brain).
      Generally, responses to acoustic pulses of the same parameter combination were
      similar within a neuronal class at the two recording sites. However, all neuronal
      classes showed significantly higher response variability and a tendency for
      higher spike activity when recorded in the dendrites. Unexpectedly, the combined
      activity of two neurons (Ascending Neurons 1 and 2) recorded in the brain
      provides a better fit to song recognition than when recorded in the thorax.
      Axonal recordings of T-shaped Neuron 1 revealed graded potentials originating in
      the brain and modulating its output in a potentially behaviourally relevant
      manner. 

PMID- 24728381
TI  - Nitrate reduction functional genes and nitrate reduction potentials persist in
      deeper estuarine sediments. Why?
AB  - Denitrification and dissimilatory nitrate reduction to ammonium (DNRA) are
      processes occurring simultaneously under oxygen-limited or anaerobic conditions,
      where both compete for nitrate and organic carbon. Despite their ecological
      importance, there has been little investigation of how denitrification and DNRA
      potentials and related functional genes vary vertically with sediment depth.
      Nitrate reduction potentials measured in sediment depth profiles along the Colne
      estuary were in the upper range of nitrate reduction rates reported from other
      sediments and showed the existence of strong decreasing trends both with
      increasing depth and along the estuary. Denitrification potential decreased along
      the estuary, decreasing more rapidly with depth towards the estuary mouth. In
      contrast, DNRA potential increased along the estuary. Significant decreases in
      copy numbers of 16S rRNA and nitrate reducing genes were observed along the
      estuary and from surface to deeper sediments. Both metabolic potentials and
      functional genes persisted at sediment depths where porewater nitrate was absent.
      Transport of nitrate by bioturbation, based on macrofauna distributions, could
      only account for the upper 10 cm depth of sediment. A several fold higher
      combined freeze-lysable KCl-extractable nitrate pool compared to porewater
      nitrate was detected. We hypothesised that his could be attributed to
      intracellular nitrate pools from nitrate accumulating microorganisms like
      Thioploca or Beggiatoa. However, pyrosequencing analysis did not detect any such
      organisms, leaving other bacteria, microbenthic algae, or foraminiferans which
      have also been shown to accumulate nitrate, as possible candidates. The
      importance and bioavailability of a KCl-extractable nitrate sediment pool remains
      to be tested. The significant variation in the vertical pattern and abundance of
      the various nitrate reducing genes phylotypes reasonably suggests differences in
      their activity throughout the sediment column. This raises interesting questions
      as to what the alternative metabolic roles for the various nitrate reductases
      could be, analogous to the alternative metabolic roles found for nitrite
      reductases. 

PMID- 24728383
TI  - Nucleophilic addition to N-alkoxyamides.
AB  - An amide group is one of the most abundant functional groups in organic
      synthesis. However, nucleophilic addition to amide carbonyls has received less
      attention than their construction due to their high stability. In this
      Perspective, we describe our recent progress with N-alkoxyamides. Incorporation
      of an N-alkoxy group as a reactivity control element into the nitrogen atom of an
      amide successfully overcomes issues inherent to the nucleophilic addition. The
      reaction can introduce two different nucleophiles in a one-pot process, giving a
      variety of substituted amines. When the Schwartz reagent was used in the first
      reduction step, high chemoselectivity was observed in the presence of sensitive
      functional groups such as esters, which resulted in the concise total synthesis
      of (+/-)-gephyrotoxin. 

PMID- 24728382
TI  - Inhibition of Sp1 functions by its sequestration into PML nuclear bodies.
AB  - Promyelocytic leukemia nuclear bodies (PML NBs) are comprised of PML and a
      striking variety of its associated proteins. Various cellular functions have been
      attributed to PML NBs, including the regulation of gene expression. We report
      here that induced expression of PML recruits Sp1 into PML NBs, leading to the
      reduction of Sp1 transactivation function. Specifically, Chromatin
      immunoprecipitation (ChIP) assay demonstrated that induced expression of PML
      significantly diminishes the amount of Sp1 binding to its target gene promoter,
      immunofluorescence staining showed dramatic increase in the co-localization
      between PML and Sp1 upon induction of PML expression, moreover, PML and Sp1 co
      fractionated in the core nuclear matrix. Our study further showed that PML
      promotes SUMOylation of Sp1 in a RING-motif-dependent manner, SUMOylation of Sp1
      facilitates physical interaction between Sp1 and PML and recruitment of Sp1 into
      the PML NBs, the SUMO binding motif of PML was also important for its interaction
      with Sp1. The results of this study demonstrate a novel mechanism by which PML
      regulates gene expression through sequestration of the transcription factor into
      PML NBs. 

PMID- 24728384
TI  - A splice mutation and mRNA decay of EXT2 provoke hereditary multiple exostoses.
AB  - BACKGROUND: Hereditary multiple exostoses (HME) is an autosomal dominant disease.
      The classical paradigm of mutation screening seeks to relate alterations in the
      exostosin glycosyltransferase genes, EXT1 and EXT2, which are responsible for
      over 70% of HME cases. However, the pathological significance of the majority of
      these mutations is often unclear. METHODS: In a Chinese family with HME, EXT1 and
      EXT2 genes were screened by direct sequencing. The consequence of a detected
      mutant was predicted by in silico analysis and confirmed by mRNA analysis. The
      EXT1 and EXT2 mRNA and protein levels and the HS patterns in the HME patients
      were compared with those in healthy controls. RESULTS: A heterozygous transition
      (c.743+1G>A) in the EXT2 gene, which co-segregated with the HME phenotype in this
      family, was identified. The G residue at position +1 in intron 4 of EXT2 was
      predicted to be a 5' donor splice site. The mRNA analysis revealed an alternative
      transcript with a cryptic splice site 5 bp downstream of the wild-type site,
      which harbored a premature stop codon. However, the predicted truncated protein
      was not detected by western blot analysis. Decay of the mutant mRNA was shown by
      clone sequencing and quantification analysis. The corresponding downregulation of
      the EXT2 mRNA will contribute to the abnormal EXT1/EXT2 ratio and HS pattern that
      were detected in the patients with HME. CONCLUSION: The heterozygous mutation
      c.743+1G>A in the EXT2 gene causes HME as a result of abnormal splicing, mRNA
      decay, and the resulting haploinsufficiency of EXT2.

PMID- 24728385
TI  - Verification of pharmacogenetics-based warfarin dosing algorithms in Han-Chinese
      patients undertaking mechanic heart valve replacement.
AB  - OBJECTIVE: To study the performance of pharmacogenetics-based warfarin dosing
      algorithms in the initial and the stable warfarin treatment phases in a cohort of
      Han-Chinese patients undertaking mechanic heart valve replacement. METHODS: We
      searched PubMed, Chinese National Knowledge Infrastructure and Wanfang databases
      for selecting pharmacogenetics-based warfarin dosing models. Patients with
      mechanic heart valve replacement were consecutively recruited between March 2012
      and July 2012. The predicted warfarin dose of each patient was calculated and
      compared with the observed initial and stable warfarin doses. The percentage of
      patients whose predicted dose fell within 20% of their actual therapeutic dose
      (percentage within 20%), and the mean absolute error (MAE) were utilized to
      evaluate the predictive accuracy of all the selected algorithms. RESULTS: A total
      of 8 algorithms including Du, Huang, Miao, Wei, Zhang, Lou, Gage, and
      International Warfarin Pharmacogenetics Consortium (IWPC) model, were tested in
      181 patients. The MAE of the Gage, IWPC and 6 Han-Chinese pharmacogenetics-based
      warfarin dosing algorithms was less than 0.6 mg/day in accuracy and the
      percentage within 20% exceeded 45% in all of the selected models in both the
      initial and the stable treatment stages. When patients were stratified according
      to the warfarin dose range, all of the equations demonstrated better performance
      in the ideal-dose range (1.88-4.38 mg/day) than the low-dose range (<1.88
      mg/day). Among the 8 algorithms compared, the algorithms of Wei, Huang, and Miao
      showed a lower MAE and higher percentage within 20% in both the initial and the
      stable warfarin dose prediction and in the low-dose and the ideal-dose ranges.
      CONCLUSIONS: All of the selected pharmacogenetics-based warfarin dosing regimens
      performed similarly in our cohort. However, the algorithms of Wei, Huang, and
      Miao showed a better potential for warfarin prediction in the initial and the
      stable treatment phases in Han-Chinese patients undertaking mechanic heart valve
      replacement.

PMID- 24728386
TI  - Preliminary molecular characterizations of Sarcoptes scaibiei (Acari:
      Sarcoptidae) from farm animals in Egypt.
AB  - Little is known about the genetic diversity of Sarcoptes scabiei mites in farm
      animals in Egypt. In this study, we characterized S. scabiei in 25 skin scrapes
      from water buffalo, cattle, sheep, and rabbits at the nuclear marker ITS2 and
      mitochondrial markers COX1 and 16S rRNA. Sequences of the ITS2 showed no host
      segregation or geographical isolation, whereas those of the mitochondrial COX1
      and 16S rRNA genes indicated the presence of both host-adapted and geographically
      segregated populations of S. scabiei. Host adaptation may limit inter-species
      transmission of. S. scabiei, thus restrict gene flow among S. scabiei from
      different hosts. This is the first report on the molecular characterization of
      sarcoptic mites in Egypt. Further genetic studies involving larger numbers of
      specimens, especially those from humans and companion animals, are needed to
      understand the molecular epidemiology of sarcoptic mange in Egypt. 

PMID- 24728388
TI  - [Systematic reviews: a key tool for clinical and health decision making].

PMID- 24728387
TI  - Septicaemia models using Streptococcus pneumoniae and Listeria monocytogenes:
      understanding the role of complement properdin.
AB  - Streptococcus pneumoniae and Listeria monocytogenes, pathogens which can cause
      severe infectious disease in human, were used to infect properdin-deficient and
      wildtype mice. The aim was to deduce a role for properdin, positive regulator of
      the alternative pathway of complement activation, by comparing and contrasting
      the immune response of the two genotypes in vivo. We show that properdin
      deficient and wildtype mice mounted antipneumococcal serotype-specific IgM
      antibodies, which were protective. Properdin-deficient mice, however, had
      increased survival in the model of streptococcal pneumonia and sepsis. Low
      activity of the classical pathway of complement and modulation of FcgammaR2b
      expression appear to be pathogenically involved. In listeriosis, however,
      properdin-deficient mice had reduced survival and a dendritic cell population
      that was impaired in maturation and activity. In vitro analyses of splenocytes
      and bone marrow-derived myeloid cells support the view that the opposing outcomes
      of properdin-deficient and wildtype mice in these two infection models is likely
      to be due to a skewing of macrophage activity to an M2 phenotype in the properdin
      deficient mice. The phenotypes observed thus appear to reflect the extent to
      which M2- or M1-polarised macrophages are involved in the immune responses to S.
      pneumoniae and L. monocytogenes. We conclude that properdin controls the strength
      of immune responses by affecting humoral as well as cellular phenotypes during
      acute bacterial infection and ensuing inflammation. 

PMID- 24728389
TI  - [Development of an Excel spreadsheet for meta-analysis of indirect and mixed
      treatment comparisons].
AB  - Meta-analyses in clinical research usually aimed to evaluate treatment efficacy
      and safety in direct comparison with a unique comparator. Indirect comparisons,
      using the Bucher's method, can summarize primary data when information from
      direct comparisons is limited or nonexistent. Mixed comparisons allow combining
      estimates from direct and indirect comparisons, increasing statistical power.
      There is a need for simple applications for meta-analysis of indirect and mixed
      comparisons. These can easily be conducted using a Microsoft Office Excel
      spreadsheet. We developed a spreadsheet for indirect and mixed effects
      comparisons of friendly use for clinical researchers interested in systematic
      reviews, but non-familiarized with the use of more advanced statistical packages.
      The use of the proposed Excel spreadsheet for indirect and mixed comparisons can
      be of great use in clinical epidemiology to extend the knowledge provided by
      traditional meta-analysis when evidence from direct comparisons is limited or
      nonexistent. 

PMID- 24728390
TI  - [Neuroticism and post-traumatic stress disorder: a meta-analytic study].
AB  - BACKGROUND: There are conflicting results on the role of neuroticism as a risk
      factor for post-traumatic stress disorder (PTSD). The objectives of this study
      were to estimate the magnitude and direction of the association between
      neuroticism and PTSD, and to analyze the influence of different moderator
      variables on effect size. METHODS: A systematic review and a meta-analysis were
      carried out. The search for studies was conducted in Medline, IME, PsycINFO, Trip
      Database, and Google Scholar, until October 2012. A hand search was also carried
      out and main researchers were contacted. INCLUSION CRITERIA: (a) empirical
      studies of the association between neuroticism and PTSD using validated scales or
      diagnostic criteria (DSM, ICD), (b) in participants exposed to a traumatic event
      and (c) written in English or Spanish. Two independent evaluators performed the
      selection and extracted the data following a previously developed protocol. The
      random-effects model was applied to obtain the mean effect size and to explore
      moderators. RESULTS: Out of 96 potential articles, 34 fulfilled the inclusion
      criteria (9,941 participants). The mean effect size was r+ = 0.371 (95%CI: 0.327
      and 0.414). Publication bias was discarded as a threat. A predictive model was
      elaborated with three variables (reporting of ethnicity, age, and type of
      sample). CONCLUSION: Neuroticism can be considered as a risk factor for PTSD in
      people who have been exposed to a traumatic event. These findings are relevant
      for developing preventive interventions and treatments.

PMID- 24728391
TI  - [Risks of dual blockade of the renin-angiotensin system compared with
      monotherapy: a systematic review and cumulative meta-analysis of randomized
      trials and observational studies].
AB  - BACKGROUND: Previous work has suggested that dual blockade using inhibitors of
      the renin-angiotensin system (RAS) would be associated with an increase in side
      effects compared to monotherapy. We reexamined the safety of dual RAS blockade,
      especially in patients at risk, and explored the stability of the evidence
      accumulated over the years. METHOD: Systematic review with random-effects meta
      analyses. We reviewed 15 previously published meta-analyses as the starting
      point. PubMed/Medline was searched for recent evidence from both observational
      and randomized controlled trials. Outcomes measures were: mortality (overall and
      cardiovascular), hyperkalemia, hypotension, renal failure, stroke, and treatment
      withdrawal due to adverse effects. We calculated relative risks (RR) and
      confidence intervals (95% CI) RESULTS: Dual RAS blockade was not associated with
      reduced relative risk (RR) overall mortality (RR:1.00, 0.96-1.05; 21 studies),
      cardiovascular mortality (RR:1.01, 0.94-1.09; 13 studies) or stroke (RR:1.02;
      0.94-1.11; 11 studies) compared to monotherapy. Dual blockade was associated with
      an increased risk of hyperkalemia (RR:1.58, 1.37-1.81; 34 studies), hypotension
      (RR:1.66; 1.41-1.95; 25 studies), renal failure (RR:1.52;1.28-1.81; 29 studies)
      and treatment discontinuation due to adverse events (RR:1.26;1.22-1.30; 37
      studies). These results were consistent in cohorts of patients with diabetes
      mellitus, kidney disease or heart failure. CONCLUSIONS: Dual RAS blockade
      increased (vs monotherapy) the risks of hyperkalemia, hypotension, renal failure
      and treatment discontinuation. Dual RAS blockade did not offer additional benefit
      in reducing overall mortality, cardiovascular mortality or stroke. These findings
      are consistent over time.

PMID- 24728392
TI  - [Evaluation of techniques in vitro immune to the diagnosis of allergy: meta
      analysis 2000-2012].
AB  - BACKGROUND: Allergies have high prevalence, affecting all age groups, generate
      negative impacts on health, educational and economic systems, and they are
      unknown the diagnostic utility of screening tests. The objective of the study was
      to evaluate the validity, performance, safety and diagnostic efficiency of in
      vitro immunological techniques for allergies, 2000-2012. METHODS: Systematic
      review with meta-analysis. We applied a search strategy studies in PubMed,
      Sciencedirect and Wiley, with search terms activation basophil test, lymphocyte
      transformation test, especific IgE immunoassay. We determined the reproducibility
      of the selection, extraction and quality assessment of articles. We calculated
      sensitivity, specificity, likelihood ratios, predictive values, proportion of
      false, accuracy, odds ratio, Youden index J and ROC curve in Meta-DiSc(es) and
      Epidat 3.0. software. RESULTS: We included 18 studies with 3520 individuals, 58%
      patients and 42% healthy. Activation of basophils showed sensitivity of 78% (95%
      CI :74-81), specificity 95% (95% CI: 83-100), positive likelihood ratio 9.9 (95%
      CI: 6.8 to 14.4) and negative of 0.20 (95% CI = 0.13 to 0.30) a diagnostic OR
      70.8 (IC95: 40.2 to 124.8) and area under the curve of 0.97. In specific
      immunoglobulin E sensitivity was 72% (95% CI: 69-75), specificity 90% (95% CI :
      88-92), positive likelihood ratio 12.9 (95% CI = 4.0 to 41.6) negative 0.32 (95%
      CI:0.23-0.43), diagnostic OR 41.6 (95% CI :11.6 to 148.9) and area under the
      curve 0.87. CONCLUSION: We showed that activation of basophils and specific IgE
      are useful tests for diagnosing allergies.

PMID- 24728393
TI  - [Impact of HIV/AIDS on quality of life: meta-analysis 2002-2012].
AB  - BACKGROUND: HIV/AIDS is a chronic infection that transcends the biological domain
      and affects social relations, mental health, financial aspects and quality of
      life. The objective of the study was to assess the perception of Health Related
      Quality Of Life (HRQOL)) in people with HIV / AIDS. METHODS: Systematic review
      with meta-analysis. We applied a research protocol in four multidisciplinary
      databases: Pubmed, Science direct, Lilacs y Scielo; with search terms WHOQOL
      BREF, WHOQOL-HIV-BREF, WHOQOLBREF-HIV. Quality assessment of articles was done by
      two researchers to ensure the completeness and reproducibility. HRQL was measured
      on a scale of 0 (worst outcome) to 100 points. The analysis was based on
      frequencies, summary measures, confidence intervals, and Student t test. RESULTS:
      The study included 19 studies with 3,348 people from 11 countries. The average of
      hrql was between 59 and 64 points, the lowest score was the environmental
      dimension with 59 points and the greater psychological health with 64 points. In
      the sensitivity analysis we found changes of 0 and 5 points between overall score
      and the observed data by excluding each individual study. We found good
      convergent validity on the dimensions common to both instruments evaluated, with
      differences of less than 3 points. CONCLUSION: hrql scores in people with
      HIV/aids were good (greater than 50) which implies that proper management can
      reduce the negative effects on the physical health, psychological health, socials
      relations, the environment, independence level and spirituality.

PMID- 24728394
TI  - [Meta-analysis of group comparison and meta-analysis of reliability
      generalization of the State-Trait Anxiety Inventory Questionnaire (STAI)].
AB  - BACKGROUND: Since its creation the STAI has been cited in more than 14,000
      documents, with more than 60 adaptations in different countries. In some
      adaptations this instrument has no clinical scores. The aim of this work is to
      determine if the State-Trait Anxiety Inventory (STAI) has higher scores in
      patients diagnosed with anxiety than in general population. In addition, we want
      to examine if the internal consistency is adequate in anxious patient samples.
      METHODS: We performed a literature search in Tripdatabase, Cochrane, Web of
      Knowledge, Scopus, PyscINFO and Scholar Google, for documents published between
      2008 y 2012. We selected 131 scientific articles to compare between patients
      diagnosed with anxiety and general population, and 25 for the generalization of
      reliability. For the analysis we used Cohen's d for means comparisons (random
      effects method) and Cronbach's alpha for the reliability generalization (fixed
      effects method). RESULTS: In the groups comparision the differences in state
      anxiety (d=1.39; CI95%: 1.22-1.56) and in the trait anxiety (d=1.74; CI95%:1.56
      1.91) were significants. The reliability for patients of some anxiety disorder
      was between 0.87 and 0.93. CONCLUSIONS: So it seems that the STAI is sensitive to
      the level of anxiety of the individual and reliable for patients with diagnosis
      of panic attack, specific phobia, social phobia, generalized social phobia,
      generalized anxiety disorder, post-traumatic stress disorder, obsessive
      compulsive disorder or acute Stress disorder.

PMID- 24728395
TI  - [Models for primary care and mental health collaboration in the care of people
      with depression: main results and methodological challenges of a systematic
      overview].
AB  - BACKGROUND: Weaknesses in the collaboration between Primary Care (PC) and Mental
      Health (MH) are a relevant problem in the care of depressed patients. It is
      necessary to analyse and appraise the existing models of collaboration to assess
      their applicability to the Spanish Health System. The aim of this study is to
      know the main characteristics of the different models of collaboration between PC
      and MH in the care of patients with depression and the quality of their
      effectiveness evidence. METHODS: Systematic overview of secondary studies
      published from 2001 to 2010 in MEDLINE, PsycINFO, Embase, LILACS, IBECS, IME and
      The Cochrane Library. Assessment of reviews applying the AMSTAR tool.
      Approximative synthesis of the quality of evidences. RESULTS: A total of 69
      studies were assessed. Quality of evidences is generally low or inconclusive due
      to the great variability among contexts and the methodological weaknesses. The
      most effective strategies integrate interventions for assigning responsibility
      for patient follow-up, redesigning management and communication/information
      sharing. Overviews of secondary studies on collaborative models facilitate access
      to published evidence, but entail important methodological challenges.
      CONCLUSION: The quality of evidences on effectiveness of PC-MH collaboration
      models in depression care is mainly low or inconclusive, and the more simplified
      are the analysis of components, processes and implementation conditions, the less
      meaningful and applicable they are.

PMID- 24728396
TI  - [Use of health services for immigrants and native population: a systematic
      review].
AB  - BACKGROUND: Spain was among the top immigration destinations globally between
      1990 and 2005, becoming in 2006 in the European country with the highest net
      migration. As a result of the migration process and the living conditions in the
      host countries, immigrants' health may be affected. Limited research has
      investigated access and use of health services for this population. The aim of
      this study was to describe the scientific evidence on the use of general and
      specialist medical services for the immigrant population compared to the native.
      METHODS: Systematic review. It has carried out a search of the national and
      international scientific literature of comparative studies on the use of general
      and specialist medical services among immigrant and native since 1994-2013. It
      was used the MEDLINE database as well as a manual search, no language limit or
      type of study. The methodological quality of the 29 studies included was
      evaluated. Subject, context, methodological and extrinsic characteristics were
      collected for comparison of the included studies. RESULTS: We selected 29 studies
      on the general practitioners' (9 from Spain) and 15 of specialist physician (7
      from Spain), they mainly used health surveys as a source of information. Analyze
      both the attendance and contact with the general practitioner / specialist by
      nationality or country of birth (among others), mostly by adjusting variables of
      need and / or socioeconomic. CONCLUSION: Overall, the immigrant population in
      Spain have a similar use of general medical services than the native population,
      and less or similar use of the specialist physician services. These results are
      in line with studies in other countries.

PMID- 24728397
TI  - [Effectiveness of different physical therapy in conservative treatment of plantar
      fasciitis: systematic review].
AB  - BACKGROUND: Plantar fasciitis is the most common disease of non-traumatic pain in
      the ankle-foot. It is more common in women aged 40-70 years and diffuse
      progressive start the foot or ankle that gradually worsens preventing progress.
      The aim of this work is to determine whether different physical therapies used in
      the conservative treatment of plantar fasciitis of at least one month duration in
      adults are effective individually and / or in combination. METHODS: A systematic
      review databases in The Cochrane Library, Medline, Lilacs, IBECS, IME, PEDro and
      ENFISPO no date restriction, in Spanish and English languages. Randomized
      controlled trials were included of adult patients diagnosed with plantar
      fasciitis, intervention studies, prospective and systematic reviews. Assessment
      of study eligibility was developed by two reviewers independently and unblinded
      standardized. To classify, we used the PEDro scale critical, form of
      methodological quality plus a critical review of each summary and if this was not
      conclusive assessment of the full text. RESULTS: 32 full-text articles were
      reviewed. Most used techniques are the stretches and shock waves, although the
      best results are obtained by combining several techniques. Shock waves are
      effective when other techniques have failed. CONCLUSION: Physical therapies used
      in the various studies have proven effective to varying degrees either to reduce
      pain or relieve the symptoms of plantar fasciitis.

PMID- 24728398
TI  - Surgeons' aims and pain assessment strategies when managing paediatric post
      operative pain: A qualitative study.
AB  - Children experience moderate to severe pain post-operatively. Nurses have been
      found to have a variety of aims in this context. Surgeons' aims when managing
      post-operative pain have not been explored. This qualitative study set out to
      explore paediatric surgeons' aims when managing post-operative pain in one
      paediatric hospital in Canada. Consultant surgeons (n = 8) across various
      specialities took part in semi-structured interviews. Surgeons' overarching aim
      was to keep the child comfortable. Various definitions of comfortable were given,
      relating to the child's experience of pain itself and their ability to undertake
      activities of daily living. Children's behavioural pain cues seem to be a primary
      consideration when making treatment decisions. Parents' views regarding their
      child's pain were also seen as important, suggesting children may not be seen as
      competent to make decisions on their own behalf. The need to maintain a realistic
      approach was emphasised and pain management described as a balancing act.
      Surgeons may draw on both tacit and explicit knowledge when assessing children's
      pain. There appears to be an expectation among surgeons that some pain is to be
      expected post-operatively and that the diagnostic value of pain may, in some
      cases, supersede concerns for the child's pain experience. 

PMID- 24728402
TI  - High-resolution adsorption analysis of pillared zeolites IPC-3PI and MCM-36.
AB  - The porous structure of pillared zeolites IPC-3PI and MCM-36 and their precursors
      IPC-3P and MCM-22P, respectively, has been investigated by means of a high
      resolution adsorption analysis. The analysis was based on argon adsorption
      isotherms measured at 87 K from the relative pressure of 10(-6). The isotherms
      were processed by means of the t-plot method, which made it possible to
      distinguish adsorption in micropores from adsorption in mesopores. The pore size
      distribution was evaluated from argon isotherms using Non-Local Density
      Functional Theory. The obtained results have shown that the microporous structure
      of the MWW layers is preserved in both pillared zeolites. In contrast to
      precursors IPC-3P and MCM-22P, pillared samples are characterized by the
      formation of a porous structure belonging to the lower mesopore region. The
      distribution of mesopores in the zeolite IPC-3PI is broader and is shifted to
      larger widths in comparison with the zeolite MCM-36. 

PMID- 24728399
TI  - General practice on-the-job training in Chinese urban community: a qualitative
      study on needs and challenges.
AB  - BACKGROUND: On-the-job training is an important strategy for general
      practitioners to deliver appropriately community health services in China. The
      development of basic professional competence for general practitioners is the
      main goal of on-the-job training program. The aim of this study was to explore
      the needs of and the challenges to on-the-job training for general practitioners,
      and to provide advices for policy-makers to carry out this program more
      effectively. METHODS: We conducted 3 nominal group techniques, 17 in-depth
      interviews and 3 focus groups to identify the status of, needs of and challenges
      to on-the-job training for general practitioners in Liaoning, Ningxia, and Fujian
      provinces from September 2011 until December 2011. Audiotapes and transcripts
      were analyzed to identify major themes. Content analysis of the data was
      completed from January 2012 to March 2012. RESULTS: Basic theoretical knowledge
      and clinical skills were the main needs for general practitioners during on-the
      job training. The challenges during training included the time contradiction
      between work and training, deficiencies of qualified preceptors, and lack of
      training funds. Participants gave recommendations how to resolve the above
      problems. CONCLUSIONS: In order to improve the outcomes of general practice on
      the-job training, it is necessary for government officials to resolve the
      contradiction between work and training, train preceptors continuously, and
      increase financial support in the training program.

PMID- 24728403
TI  - Abattoirs as non-hospital source of extended spectrum beta lactamase producers:
      confirmed by the double disc synergy test and characterized by matrix-assisted
      laser desorption/ionization time of flight mass spectrometry.
AB  - In this study, the presence of extended spectrum beta lactamase (ESBL) producing
      organisms in abattoirs, a non-hospital community was investigated. The presence
      of ESBL-producing phenotypes was confirmed by the Double Disc Synergy Test
      (DDST). Out of the 99 isolates screened for ESBL, 28 (28.3%) were confirmed
      positive. The positive isolates were characterised by using Matrix-Assisted Laser
      Desorption/Ionization Time of flight Mass Spectrometry. 50% of the isolates were
      Pseudomonas spp., the rest were different species of Acinetobacter,
      Stenotrophomonas and Achromobacter. Pseudomonas monteilli and Pseudomonas putida
      were the most occurring in the intestine. The entire positive ESBL producers were
      subjected to plasmid curing to ascertain the location of the resistant marker.
      The result of the plasmid curing indicated that the resistant genes were
      chromosomally borne. The findings have therefore established the presence of ESBL
      producing organisms in the gut of animals from abattoirs and the table were the
      meat are sold, and its rate of occurrence is comparable to hospital ICUs.
      Abattoir communities could probably be a source of human infection with ESBL
      expressing pathogens and possible transfer to non-ESBL producers. 

PMID- 24728404
TI  - Correlated fluorine diffusion and ionic conduction in the nanocrystalline F(-)
      solid electrolyte Ba(0.6)La(0.4)F(2.4)-(19)F T1(rho) NMR relaxation vs.
      conductivity measurements.
AB  - Chemical reactions induced by mechanical treatment may give access to new
      compounds whose properties are governed by chemical metastability, defects
      introduced and the size effects present. Their interplay may lead to
      nanocrystalline ceramics with enhanced transport properties being useful to act
      as solid electrolytes. Here, the introduction of large amounts of La into the
      cubic structure of BaF2 served as such an example. The ion transport properties
      in terms of dc-conductivity values of the F(-) anion conductor Ba1-xLaxF2+x (here
      with x = 0.4) considerably exceed those of pure, nanocrystalline BaF2. So far,
      there is only little knowledge about activation energies and jump rates of the
      elementary hopping processes. Here, we took advantage of both impedance
      spectroscopy and (19)F NMR relaxometry to get to the bottom of ion jump diffusion
      proceeding on short-range and long-range length scales in Ba0.6La0.4F2.4. While
      macroscopic transport is governed by an activation energy of 0.55 to 0.59 eV, the
      elementary steps of hopping seen by NMR are characterised by much smaller
      activation energies. Fortunately, we were able to deduce an F(-) self-diffusion
      coefficient by the application of spin-locking NMR relaxometry. 

PMID- 24728405
TI  - Substrate modulation of fatty acid effects on energization and respiration of
      kidney proximal tubules during hypoxia/reoxygenation.
AB  - Kidney proximal tubules subjected to hypoxia/reoxygenation develop a
      nonesterified fatty acid-induced energetic deficit characterized by persistent
      partial mitochondrial deenergization that can be prevented and reversed by citric
      acid cycle substrates. To further assess the role of competition between fatty
      acids and substrates on inner membrane substrate carriers in the deenergization
      and the contribution to deenergization of fatty acid effects on respiratory
      function, digitonin-permeabilized rabbit and mouse tubules were studied using
      either addition of exogenous oleate after control normoxic incubation or
      increases of endogenous fatty acids produced by hypoxia/reoxygenation. The
      results demonstrated major effects of matrix oxaloacetate accumulation on
      succinate-supported energization and respiration and their modification by fatty
      acids. Improvements of energization in the presence of fatty acids by glutamate
      were shown to result predominantly from lowering matrix oxaloacetate rather than
      from amelioration of transmembrane cycling of fatty acids and uncoupling. Mouse
      tubules had 2.5 fold higher rates of succinate utilization, which resulted in
      stronger effects of oxaloacetate accumulation than rabbit tubules.
      Hypoxia/reoxygenation induced respiratory inhibition that was more severe for
      complex I-dependent substrates. Fatty acids themselves did not acutely contribute
      to this respiratory inhibition, but lowering them during 60 min. reoxygenation to
      allow recovery of ATP during that period alleviated it. These data clarify the
      basis for the nonesterified fatty acid-induced mitochondrial energetic deficit in
      kidney proximal tubules that impairs structural and functional recovery and
      provide insight into interactions that need to be considered in the design of
      substrate-based interventions to improve mitochondrial function. 

PMID- 24728406
TI  - Incidence and determinants of nevirapine and efavirenz-related skin rashes in
      West Africans: nevirapine's epitaph?
AB  - Non-nucleoside reverse transcriptase inhibitor (NNRTI) associated rash is common
      and frequently leads to discontinuation of NNRTIs. This study assessed the risk
      of developing rashes and discontinuing NNRTIs and associated factors in a large
      clinic in central Ghana. In this retrospective cohort study, clinical data were
      obtained in patients starting efavirenz or nevirapine between 2004-2010. Factors
      associated with rashes were explored using a multivariate Cox proportional
      hazards regression model. Of 3,999 patients who started NNRTI-based ART, 281
      (7.0%) experienced at least one episode of NNRTI-related rash with an incidence
      of 2.63 events/100 person-years, occurring in 10.2% and 5.6% of patients taking
      nevirapine and efavirenz respectively. Most rashes (94%) were grade 1 or 2 and
      were reported a median of 2 months following initiation of ART. In multivariate
      analysis developing a rash was associated with nevirapine use (aHR 1.67, 95% CI
      1.28-2.10), female gender (aHR of 1.39, 95% CI 1.01-1.92) and lower baseline CD4
      counts (aHR 0.88, 95% CI 0.82-0.95 per 50 cells/mm3 increment). Patients with
      nevirapine-associated rash were 11 times more likely to discontinue treatment as
      patients with efavirenz-associated rash. In contrast to findings in other
      studies, NNRTI-associated rashes in Ghanaians appear more common in patients with
      lower baseline CD4 counts. Given the increased frequency of rashes with
      nevirapine and subsequent discontinuations in many patients, along with other
      treatment-limiting toxicities, this provides further impetus for the replacement
      of nevirapine by efavirenz as the first-line NNRTI treatment of choice in Africa.

PMID- 24728408
TI  - Enhanced cold field emission of large-area arrays of vertically aligned ZnO
      nanotapers via sharpening: experiment and theory.
AB  - Large-area arrays of vertically aligned ZnO-nanotapers with tailored taper angle
      and height are electrodeposited on planar Zn-plate via continuously tuning the
      Zn(NH3)4(NO3)2 concentration in the electrolyte. Experimental measurements reveal
      that the field-emission performance of the ZnO-nanotaper arrays is enhanced with
      the sharpness and height of the ZnO-nanotapers. Theoretically, the ZnO-nanotaper
      is simplified to a "charge disc" model, based on which the characteristic
      macroscopic field enhancement factor (gammaC) is quantified. The theoretically
      calculated gammaC values are in good agreement with the experimental ones
      measured from arrays of ZnO-nanotapers with a series of geometrical parameters.
      The ZnO-nanotaper arrays have promising potentials in field-emission. The
      electrochemical synthetic strategy we developed may be extended to nanotaper
      arrays of other materials that are amenable to electrodeposition, and the "charge
      disc" model can be used for quasi-one-dimensional field emitters of other
      materials with nano-sized diameters. 

PMID- 24728407
TI  - Analysis of plant-bacteria interactions in their native habitat: bacterial
      communities associated with wild tobacco are independent of endogenous jasmonic
      acid levels and developmental stages.
AB  - Jasmonic acid (JA) mediates defense responses against herbivores and necrotrophic
      pathogens but does it influence the recruitment of bacterial communities in the
      field? We conducted field and laboratory experiments with transformed Nicotiana
      attenuata plants deficient in jasmonate biosynthesis (irAOC) and empty vector
      controls (EV) to answer this question. Using both culture-dependent and
      independent techniques, we characterized root and leaf-associated bacterial
      communities over five developmental stages, from rosette through flowering of
      plants grown in their natural habitat. Based on the pyrosequencing results, alpha
      and beta diversity did not differ among EV and irAOC plants or over ontogeny, but
      some genera were more abundant in one of the genotypes. Furthermore, bacterial
      communities were significantly different among leaves and roots. Taxa isolated
      only from one or both plant genotypes and hence classified as 'specialists' and
      'generalists' were used in laboratory tests to further evaluate the patterns
      observed from the field. The putative specialist taxa did not preferentially
      colonize the jasmonate-deficient genotype, or alter the plant's elicited
      phytohormone signaling. We conclude that in N. attenuata, JA signaling does not
      have a major effect on structuring the bacterial communities and infer that
      colonization of plant tissues is mainly shaped by the local soil community in
      which the plant grows. 

PMID- 24728409
TI  - The effects of socioeconomic status, clinical factors, and genetic ancestry on
      pulmonary tuberculosis disease in northeastern Mexico.
AB  - Diverse socioeconomic and clinical factors influence susceptibility to
      tuberculosis (TB) disease in Mexico. The role of genetic factors, particularly
      those that differ between the parental groups that admixed in Mexico, is unclear.
      The objectives of this study are to identify the socioeconomic and clinical
      predictors of the transition from latent TB infection (LTBI) to pulmonary TB
      disease in an urban population in northeastern Mexico, and to examine whether
      genetic ancestry plays an independent role in this transition. We recruited 97
      pulmonary TB disease patients and 97 LTBI individuals from a public hospital in
      Monterrey, Nuevo Leon. Socioeconomic and clinical variables were collected from
      interviews and medical records, and genetic ancestry was estimated for a subset
      of 142 study participants from 291,917 single nucleotide polymorphisms (SNPs). We
      examined crude associations between the variables and TB disease status.
      Significant predictors from crude association tests were analyzed using
      multivariable logistic regression. We also compared genetic ancestry between LTBI
      individuals and TB disease patients at 1,314 SNPs in 273 genes from the TB
      biosystem in the NCBI BioSystems database. In crude association tests, 12
      socioeconomic and clinical variables were associated with TB disease.
      Multivariable logistic regression analyses indicated that marital status,
      diabetes, and smoking were independently associated with TB status. Genetic
      ancestry was not associated with TB disease in either crude or multivariable
      analyses. Separate analyses showed that LTBI individuals recruited from hospital
      staff had significantly higher European genetic ancestry than LTBI individuals
      recruited from the clinics and waiting rooms. Genetic ancestry differed between
      individuals with LTBI and TB disease at SNPs located in two genes in the TB
      biosystem. These results indicate that Monterrey may be structured with respect
      to genetic ancestry, and that genetic differences in TB susceptibility in
      parental populations may contribute to variation in disease susceptibility in the
      region. 

PMID- 24728410
TI  - Immunosuppression in acutely decompensated cirrhosis is mediated by prostaglandin
      E2.
AB  - Liver disease is one of the leading causes of death worldwide. Patients with
      cirrhosis display an increased predisposition to and mortality from infection due
      to multimodal defects in the innate immune system; however, the causative
      mechanism has remained elusive. We present evidence that the cyclooxygenase (COX)
      derived eicosanoid prostaglandin E2 (PGE2) drives cirrhosis-associated
      immunosuppression. We observed elevated circulating concentrations (more than
      seven times as high as in healthy volunteers) of PGE2 in patients with acute
      decompensation of cirrhosis. Plasma from these and patients with end-stage liver
      disease (ESLD) suppressed macrophage proinflammatory cytokine secretion and
      bacterial killing in vitro in a PGE2-dependent manner via the prostanoid type E
      receptor-2 (EP2), effects not seen with plasma from patients with stable
      cirrhosis (Child-Pugh score grade A). Albumin, which reduces PGE2
      bioavailability, was decreased in the serum of patients with acute decompensation
      or ESLD (<30 mg/dl) and appears to have a role in modulating PGE2-mediated immune
      dysfunction. In vivo administration of human albumin solution to these patients
      significantly improved the plasma-induced impairment of macrophage
      proinflammatory cytokine production in vitro. Two mouse models of liver injury
      (bile duct ligation and carbon tetrachloride) also exhibited elevated PGE2,
      reduced circulating albumin concentrations and EP2-mediated immunosuppression.
      Treatment with COX inhibitors or albumin restored immune competence and survival
      following infection with group B Streptococcus. Taken together, human albumin
      solution infusions may be used to reduce circulating PGE2 levels, attenuating
      immune suppression and reducing the risk of infection in patients with acutely
      decompensated cirrhosis or ESLD. 

PMID- 24728411
TI  - REDD1 is essential for stress-induced synaptic loss and depressive behavior.
AB  - Major depressive disorder (MDD) affects up to 17% of the population, causing
      profound personal suffering and economic loss. Clinical and preclinical studies
      have revealed that prolonged stress and MDD are associated with neuronal atrophy
      of cortical and limbic brain regions, but the molecular mechanisms underlying
      these morphological alterations have not yet been identified. Here, we show that
      stress increases levels of REDD1 (regulated in development and DNA damage
      responses-1), an inhibitor of mTORC1 (mammalian target of rapamycin complex-1;
      ref. 10), in rat prefrontal cortex (PFC). This is concurrent with a decrease in
      phosphorylation of signaling targets of mTORC1, which is implicated in protein
      synthesis-dependent synaptic plasticity. We also found that REDD1 levels are
      increased in the postmortem PFC of human subjects with MDD relative to matched
      controls. Mutant mice with a deletion of the gene encoding REDD1 are resilient to
      the behavioral, synaptic and mTORC1 signaling deficits caused by chronic
      unpredictable stress, whereas viral-mediated overexpression of REDD1 in rat PFC
      is sufficient to cause anxiety- and depressive-like behaviors and neuronal
      atrophy. Taken together, these postmortem and preclinical findings identify REDD1
      as a critical mediator of the atrophy of neurons and depressive behavior caused
      by chronic stress exposure. 

PMID- 24728414
TI  - ESSKA from Berlin 1984 to Barcelona 2016: "from a resident to a President".

PMID- 24728412
TI  - Paracrine effects of stem cells in wound healing and cancer progression (Review).
AB  - Stem cells play an important role in tissue repair and cancer development. The
      capacity to self-renew and to differentiate to specialized cells allows tissue
      specific stem cells to rebuild damaged tissue and cancer stem cells to initiate
      and promote cancer. Mesenchymal stem cells, attracted to wounds and cancer,
      facilitate wound healing and support cancer progression primarily by secreting
      bioactive factors. There is now growing evidence that, like mesenchymal stem
      cells, also tissue-specific and cancer stem cells manipulate their environment by
      paracrine actions. Soluble factors and microvesicles released by these stem cells
      have been shown to protect recipient cells from apoptosis and to stimulate
      neovascularization. These paracrine mechanisms may allow stem cells to
      orchestrate wound healing and cancer progression. Hence, understanding these stem
      cell-driven paracrine effects may help to improve tissue regeneration and cancer
      treatment. 

PMID- 24728415
TI  - The correlation between anterior cruciate ligament injury in elite alpine skiers
      and their parents.
AB  - PURPOSE: The aim of this study was to investigate whether a familiar correlation
      with anterior cruciate ligament (ACL) injury exists between competitive alpine
      skiers and their parents. METHODS: All 593 (293 males, 300 females) elite alpine
      skiers who have studied at a Swedish alpine Ski High School during 2006 and 2012
      answered a questionnaire whether they or their parents had suffered an ACL
      injury. A total of 418 skiers (70%) answered the questionnaire. RESULTS: Twenty
      nine per cent (n = 19) out of the 65 ACL-injured skiers reported that they had a
      parent (mother or father) who have had an ACL injury. In skiers without an ACL
      injury (n = 353), the result was 18% (n = 64). An odds ratio of 1.95 (95%
      confidence interval 1.04-3.65) was found to suffer an ACL injury if you have a
      parent who has had an ACL injury compared with if you have a parent without any
      ACL injury. CONCLUSION: The findings of the current study demonstrated a family
      history to tear the ACL between alpine skiers who had studied at a Swedish Ski
      High School and ACL injuries of their parents. LEVEL OF EVIDENCE: III.

PMID- 24728416
TI  - Circulating irisin levels are not affected by coffee intake: a randomized
      controlled trial.
AB  - Irisin, secreted by skeletal muscle and possibly fat, is hypothesized to play an
      important role in modulating energy expenditure, obesity and metabolism. Coffee
      consumption also increases energy expenditure and leads to positive metabolic
      effects, but whether these effects are mediated by irisin remains unknown. The
      objective of this study was to determine the association between baseline irisin
      levels and the metabolic profile in humans and to investigate whether consumption
      of caffeinated coffee alters irisin levels. To this end, a secondary analysis was
      performed investigating irisin levels at baseline and after eight weeks in 32
      healthy, overweight coffee drinkers who were randomized to consumption of 5 cups
      per day of instant caffeinated coffee, decaffeinated coffee, or water. Spearman
      correlation and analysis of covariance analyses were performed to identify
      possible associations. Irisin levels were positively correlated with waist
      circumference (r = 0.41, p = 0.02), fat mass (r = 0.44, p = 0.01) and CRP (r =
      0.47, p = 0.007). Though there was a trend towards increased levels of irisin
      over time in the caffeinated coffee group (+1.8%) when compared to the placebo
      group (24%) this did not reach statistical significance (p = 0.75 for the trend).
      This first randomized trial failed to reveal any effects of coffee consumption on
      irisin levels, but a larger trial, appropriately sized on the basis of data
      provided by this study, is needed to conclusively investigate such a
      relationship. TRIAL REGISTRATION: Clinicaltrials.gov NCT00305097.

PMID- 24728417
TI  - Molecular photo-oscillators based on highly accelerated heterocyclic azo dyes in
      nematic liquid crystals.
AB  - Benzothiazole-pyrrole-based azo dyes greatly enhance their thermal isomerisation
      rate by up to 160 times when they are under the influence of the nematic mean
      field yielding the LC-based photochromic oscillators with the highest oscillation
      frequencies reported so far (2.6 kHz at 298 K). 

PMID- 24728418
TI  - Long QT syndrome type 8: novel CACNA1C mutations causing QT prolongation and
      variant phenotypes.
AB  - AIMS: CACNA1C mutations have been reported to cause LQTS type 8 (LQT8; Timothy
      syndrome), which exhibits severe phenotypes, although the frequency of patients
      with LQT8 exhibiting only QT prolongation is unknown. This study aimed to
      elucidate the frequency of CACNA1C mutations in patients with long QT syndrome
      (LQTS), except those with Timothy syndrome and investigate phenotypic variants.
      METHODS AND RESULTS: CACNA1C gene screening was performed in 278 probands
      negative for LQTS-related gene mutations. Functional analysis of mutant channels
      using a whole-cell patch-clamp technique was also performed. Using genetic
      screening, we identified five novel CACNA1C mutations: P381S, M456I, A582D,
      R858H, and G1783C in seven (2.5%) unrelated probands. Seven mutation carriers
      showed alternative clinical phenotypes. Biophysical assay of CACNA1C mutations
      revealed that the peak calcium currents were significantly larger in R858H mutant
      channels than those of wild-type (WT). In contrast, A582D mutant channels
      displayed significantly slower inactivation compared with WT. The two mutant
      channels exerted different gain-of-function effects on calcium currents.
      CONCLUSION: In patients with LQTS, the frequency of CACNA1C mutations was higher
      than reported. Even without typical phenotypes of Timothy syndrome, CACNA1C
      mutations may cause QT prolongation and/or fatal arrhythmia attacks.

PMID- 24728419
TI  - Author reply: To PMID 24394973.

PMID- 24728420
TI  - Are RYR2 exon-3 deletions truly causative for non-compaction?

PMID- 24728421
TI  - Facile fabrication and enhanced photosensitized degradation performance of the g
      C3N4-Bi2O2CO3 composite.
AB  - Flower-like Bi2O2CO3 and g-C3N4-Bi2O2CO3 microspheres with a high adsorption
      ability were synthesized using a facile method, and their dye-induced
      photosensitized degradation activity under visible light irradiation was
      evaluated. The as-synthesized samples were characterized by XRD, FT-IR, FESEM,
      TEM (HRTEM), UV-vis DRS and nitrogen adsorption-desorption techniques. It was
      found that the activity of Bi2O2CO3 was significantly enhanced due to the
      generation of g-C3N4-Bi2O2CO3 heterostructures. The dye-sensitization and the
      presence of g-C3N4 are beneficial for the visible-light excited process. The
      enhancement of photocatalytic performance is ascribed to the proper matching of
      the energy levels of the dye, Bi2O2CO3 and g-C3N4 that facilitates the separation
      and transfer of photogenerated electrons and holes at the heterojunctions. The
      results of the present study give insights that are beneficial for the design of
      heterostructured materials. 

PMID- 24728422
TI  - Mice lacking mitochondrial ferritin are more sensitive to doxorubicin-mediated
      cardiotoxicity.
AB  - Mitochondrial ferritin is a functional ferritin that localizes in the
      mitochondria. It is expressed in the testis, heart, brain, and cells with active
      respiratory activity. Its overexpression in cultured cells protected against
      oxidative damage and reduced cytosolic iron availability. However, no overt
      phenotype was described in mice with inactivation of the FtMt gene. Here, we used
      the doxorubicin model of cardiac injury in a novel strain of FtMt-null mice to
      investigate the antioxidant role of FtMt. These mice did not show any evident
      phenotype, but after acute treatment to doxorubicin, they showed enhanced
      mortality and altered heart morphology with fibril disorganization and severe
      mitochondrial damage. Signs of mitochondrial damage were present also in mock
      treated FtMt(-/-) mice. The hearts of saline- and doxorubicin-treated FtMt(-/-)
      mice had higher thiobarbituric acid reactive substance levels, heme oxygenase 1
      expression, and protein oxidation, but did not differ from FtMt(+/+) in the
      cardiac damage marker B-type natriuretic peptide (BNP), ATP levels, and
      apoptosis. However, the autophagy marker LC3 was activated. The results show that
      the absence of FtMt, which is highly expressed in the heart, increases the
      sensitivity of heart mitochondria to the toxicity of doxorubicin. This study
      represents the first in vivo evidence of the antioxidant role of FtMt. KEY
      MESSAGE: Mitochondrial ferritin (FtMt) expressed in the heart has a protective
      antioxidant role. Acute treatment with doxorubicin caused the death of all FtMt(
      /-) and only of 60 % FtMt(+/+) mice. The hearts of FtMt(-/-) mice showed fibril
      disorganization and mitochondrial damage. Markers of oxidative damage and
      autophagy were increased in FtMt(-/-) hearts. This is the first in vivo evidence
      of the antioxidant role of FtMt.

PMID- 24728423
TI  - Synthesis and evaluation of monophosphoryl lipid A derivatives as fully synthetic
      self-adjuvanting glycoconjugate cancer vaccine carriers.
AB  - A fully synthetic carbohydrate-based cancer vaccine is an attractive concept, but
      an important topic in the area is to develop proper vaccine carriers that can
      improve the immunogenicity and other immunological properties of tumor-associated
      carbohydrate antigens (TACAs). In this context, four monophosphoryl derivatives
      of Neisseria meningitidis lipid A were synthesized via a highly convergent and
      effective strategy and evaluated as vaccine carriers and adjuvants. The
      conjugates of these monophosphoryl lipid A (MPLA) derivatives with a modified
      form of the sTn antigen were found to elicit high titers of antigen-specific IgG
      antibodies, indicating a T cell-dependent immune response, in the absence of an
      external adjuvant. It was concluded that MPLAs could be utilized as potent
      vaccine carriers and built-in adjuvants to create fully synthetic self
      adjuvanting carbohydrate-based cancer vaccines. The lipid composition and
      structure of MPLA were shown to have a significant influence on its immunological
      activity, and among the MPLAs examined, natural N. meningitidis MPLA exhibited
      the most promising properties. Moreover, Titermax Gold, a conventional vaccine
      adjuvant, was shown to inhibit, rather than promote, the immunological activity
      of MPLA conjugates, maybe via interacting with MPLA. 

PMID- 24728424
TI  - Exercise testing in children with Wolff-Parkinson-White syndrome: what is its
      value?
AB  - This study was conducted to evaluate the accuracy of exercise testing for
      predicting accessory pathway characteristics in children with Wolff-Parkinson
      White (WPW) syndrome. The study enrolled 37 children with WPW syndrome and
      candidates for invasive electrophysiologic study (EPS). Exercise testing was
      performed for all the study participants before the invasive study. Data from the
      invasive EPS were compared with findings from the exercise testing. The sudden
      disappearance of the delta (Delta) wave was seen in 10 cases (27 %). No
      significant correlation was found between the Delta wave disappearance and the
      antegrade effective refractory period of the accessory pathway (AERP-AP) or the
      shortest pre-excited RR interval (SPERRI). The sensitivity, specificity, and
      positive and negative predictive values of Delta wave disappearance, based on
      AERP-AP as gold standard, were respectively 29.4, 80, 71.4, and 40 %. The
      corresponding values with SPERRI as the gold standard were respectively 23.8,
      71.4, 71.4 and 23.8 %. Exercise testing has a medium to low rate of accuracy in
      detecting low-risk WPW syndrome patients in the pediatric age group.

PMID- 24728425
TI  - [Clinical experience with 53 consecutive heart transplants].
AB  - INTRODUCTION: Heart transplantation is the therapy of choice for advance heart
      failure. Our group developed two transplant programs at Instituto Nacional del
      Torax and Clinica Davila. We report our clinical experience based on distinctive
      clinical policies. PATIENTS AND METHODS: Fifty-three consecutive patients were
      transplanted between November 2008 and April 2013, representing 51% of all
      Chilean cases. Distinctive clinical policies include intensive donor management,
      generic immunosuppression and VAD (ventricular assist devices) insertion.
      RESULTS: Ischemic or dilated cardiomyopathy were the main indications (23 (43%)
      each), age 48 +/- 13 years and 48 (91%) were male. Transplant listing Status: IA
      14 (26%) (VAD or 2 inotropes), IB 14 (26%) (1 inotrope) and II25 (47%) (no
      inotrope). Mean waiting time 70 +/- 83 days. Twelve (24%) were transplanted
      during VAD support (median support: 36 days). OPERATIVE TECHNIQUE: orthotopic
      bicaval transplant with ischemia time: 175 +/- 54 min. Operative mortality: 3
      (6%), all due to right ventricular failure. Re-exploration for bleeding 2 (4%),
      stroke 3 (6%), mediastinitis 0 (0%), pneumonia 4 (8%), and transient dialysis 6
      (11%). Mean follow-up was 21 +/- 14 months. Three-year survival was 86 +/- 6%.
      One patient died of Pneumocystis jirovecii pneumonia and the other died suddenly
      (non-compliance). Freedom from rejection requiring specific therapy was 80 +/- 7%
      at 3 years of follow-up. Four hundred eighty four endomyocardial biopsies were
      done: 11 (2.3%) had 2R rejection. All survivors are in NYHA (New York Heart
      Association) functional class I and all but one have normal biventricular
      function. CONCLUSION: Mid-term results are similar to those reported by the
      registry of the International Society for Heart and Lung Transplantation. This
      experience has a higher proportion of VAD support than previous national series.
      Rejection rates are low in spite of generic immunosuppression.

PMID- 24728426
TI  - [Preablative serum thyroglobulin as predictor of disease-free survival in
      differentiated thyroid cancer].
AB  - BACKGROUND: Serum thyroglobulin (sTg) is an excellent marker of persistence or
      recurrence of disease in differentiated thyroid cancer (DTC), however its role as
      prognostic factor has not been fully established. AIM: To assess the value of the
      preablative thyroglobulin (pTg) as predictor of disease-free survival in DTC.
      PATIENTS AND METHODS: Retrospective study of 104 patients with low and
      intermediate risk DTC subjected to total thyroidectomy and 131iodine ablation.
      TSH, pTg and thyroglobulin antibodies (AbTg) were determined by
      chemiluminescence. Patients with distant metastases or presence of AbTg were
      excluded. Results were analyzed using receiving operating characteristic (ROC)
      curves. RESULTS: During the 40 +/- 29 months of follow-up (range 6-132), 14 of
      104 (13%) patients had recurrence of disease. pTg was an independent indicator to
      predict disease-free survival. Using a pTg cutoff of < 10 ng/ml the negative
      predictive value was 99%, sensitivity 93%, specificity 82%, positive likelihood
      ratio (LR) 5.2 and negative LR 0,087. CONCLUSIONS: pTg value is useful as a
      prognostic marker in predicting disease-free survival in DTC patients with low or
      intermediate risk of recurrence.

PMID- 24728427
TI  - [Intensive care admissions due to severe maternal morbidity].
AB  - BACKGROUND: Maternal morbidity is a quality of care indicator. The frequency of
      severe maternal morbidity that requires an intensive care management has
      increased, due to an increase in maternal age. AIM: To describe the severe and
      acute maternal morbidity spectrum that requires an intensive care management in a
      University Hospital. MATERIAL AND METHODS: Review of medical records of 89
      pregnant women with a mean age of 29 years, admitted to an Intensive Care Unit
      (UCI) between 2006 and 2010. RESULTS: Mean gestational age on admission was 32
      weeks. The main comorbidities identified were chronic hypertension (13.5%),
      hypothyroidism (4.5%) and coagulopathies (6.7%). Severe preeclampsia, sepsis and
      obstetric hemorrhage were the main causes of admission. Length of stay ranged
      from 1 to 28 days. Seventy eight percent of patients were admitted in the
      immediate postnatal period. Mechanical ventilation was required in 24% of
      patients for a median of three days. The longer unit lengths of stay were
      observed in patients with preeclampsia and non-obstetric severe sepsis
      (pyelonephritis and pneumonia). Seven abortions and seven perinatal deaths were
      recorded. The latter were mainly secondary to severe preeclampsia/ HELLP
      syndrome. Neonatal morbidity was related to prematurity (19% hyaline membrane,
      18% persistent ductus and 4% cerebral hemorrhage). There were no maternal deaths.
      CONCLUSIONS: Preeclampsia and its complications were the main causes of maternal
      ICU admission. In this series, there were no maternal deaths and the perinatal
      survival rate was 92%.

PMID- 24728428
TI  - Patterns of left ventricular remodeling among patients with essential and
      secondary hypertension.
AB  - BACKGROUND: High blood pressure causes left ventricular hypertrophy, which is a
      negative prognostic factor among hypertensive patients. AIM: To assess left
      ventricular geometric remodeling patterns in patients with essential hypertension
      or with hypertension secondary to parenchymal renal disease. MATERIAL AND
      METHODS: We analyzed data from echocardiograms performed in 250 patients with
      essential hypertension (150 females) and 100 patients with secondary hypertension
      (60 females). The interventricular septum and the left ventricular posterior wall
      thickness were measured in the parasternal long-axis. Left ventricular mass was
      calculated using the Devereaux formula. RESULTS: The most common remodeling type
      in females and males with essential hypertension were eccentric and concentric
      left ventricular hypertrophy (cLVH), respectively. Among patients with secondary
      arterial hypertension, cLVH was most commonly observed in both genders. The
      prevalence of left ventricular hypertrophy was higher among patients with
      secondary hypertension. The left ventricular mass index and the relative left
      ventricular wall thickness were higher in males and also in the secondary
      hypertension group. Age, blood pressure values and the duration of hypertension,
      influenced remodeling patterns. CONCLUSIONS: We documented a higher prevalence of
      LVH among patients with secondary hypertension. The type of ventricular
      remodeling depends on gender, age, type of hypertension, blood pressure values
      and the duration of hypertension.

PMID- 24728429
TI  - [Quality of DNA from archival pathological samples of gallbladder cancer].
AB  - BACKGROUND: The quality of the archival samples stored at pathology services
      could be a limiting factor for molecular biology studies. AIM: To determine the
      quality of DNA extracted from gallbladder cancer samples at different
      institutions. MATERIAL AND METHODS: One hundred ninety four samples coming from
      five medical centers in Chile, were analyzed. DNA extraction was quantified
      determining genomic DNA concentration. The integrity of DNA was determined by
      polymerase chain reaction amplification of different length fragments of a
      constitutive gene (beta-globin products of 110, 268 and 501 base pairs). RESULTS:
      The mean DNA concentration obtained in 194 gallbladder cancer samples was 48 +/-
      43.1 ng/ul. In 22% of samples, no amplification was achieved despite obtaining a
      mean DNA concentration of 58.3 ng/ul. In 81, 67 and 22% of samples, a DNA
      amplification of at least 110, 268 or 501 base pairs was obtained, respectively.
      No differences in DNA concentration according to the source of the samples were
      demonstrated. However, there were marked differences in DNA integrity among
      participating centers. Samples from public hospitals were of lower quality than
      those from private clinics. CONCLUSIONS: Despite some limitations, in 80% of
      cases, the integrity of DNA in archival samples from pathology services in our
      country would allow the use of molecular biology techniques.

PMID- 24728430
TI  - [Characteristics and results of breast cancer in elderly females treated with
      curative intent].
AB  - BACKGROUND: Aging is the main risk factor to acquire breast cancer (BC).
      Nevertheless BC in elderly patients is sub-represented in clinical trials. AIM:
      To describe the clinical characteristics and long term treatment results of
      localized BC in older women. MATERIAL AND METHODS: Review of medical records of
      65 women aged 70 to 88 years, with localized BC, treated with surgery,
      postoperative radiotherapy or systemic therapy at a Clinical Hospital in Chile.
      RESULTS: The presence of symptoms or abnormal findings on physical examination
      were the main reasons for consulting in 65% of cases. Compared with tumors
      detected on physical examination, those detected using screening mammogram were
      smaller and were in stage 1 with a higher frequency (18 and 59% respectively, p <
      0.01). The pathological type was luminal in 80% of cases. Overall survival was
      better for luminal pathological type. All patients completed radiotherapy without
      interruptions developing minor acute toxicity. The most common co-morbidity was
      high blood pressure occurring in 46% of patients. Thirteen percent of patients
      had three or more co-morbidities. After a median follow up of 7 years, 23 (35%)
      patients had died and the cause of death was BC in 43% of cases. Two patients
      died of lung cancer. No patient had a local breast relapse. CONCLUSIONS:
      Screening mammogram in older women detected smaller tumors and it was associated
      with a better survival. BC is the ultimate cause of death in approximately half
      of cases.

PMID- 24728431
TI  - [Association between obstetric factors, hormone levels and nutritional status
      with the development of breast cancer].
AB  - BACKGROUND: Recent studies suggest that the age at first pregnancy, number of
      children and the lapse between births may protect against breast cancer.
      Furthermore, serum levels of estrogen, prolactin and progesterone appear to
      contribute to the development of this tumors in obese women. AIM: To verify
      whether the variables age at first pregnancy, number of children, birth interval,
      hormone levels and nutritional status are associated with the age at diagnosis of
      breast cancer. MATERIAL AND METHODS: Retrospective analysis of medical records of
      550 female patients, diagnosed and treated for breast cancer at a hospital in
      Spain between 2009 and 2012. RESULTS: We found a significant and positive
      association between age at diagnosis of cancer and the variables age at first
      pregnancy, parity and interval between pregnancies. There was also a significant
      correlation (p < 0.000) between serum levels of estrogen, prolactin and
      progesterone and nutritional status of patients. CONCLUSIONS: In this sample, age
      at first pregnancy or number of children, hormone levels and nutritional status
      are related to the age of onset of cancer.

PMID- 24728432
TI  - [Factorial structure of WHOQoL-Bref quality of life questionnaire].
AB  - BACKGROUND: The real value of quality of life instruments must be tested in local
      populations before recommending their widespread use. AIM: To assess the
      factorial structure of the quality of life questionnaire proposed by the World
      Health Organization (WHO), WHOQoL-Bref. MATERIAL AND METHODS: The questionnaire
      was answered by 2016 individuals aged between 20 and 59 years, from diverse
      public and social organizations of a city in Northern Chile. The confidence and
      factorial structure of the instrument were evaluated. RESULTS: The internal
      consistency of the instrument, according to Cronbach's alpha was 0.89. The
      adjustment of values to a model with four factors proposed by the WHO was
      moderate. The root mean square (RMS) and root mean square error of approximation
      (RMSEA) values of0.043 and 0.061, indicate a good adjustment of the model.
      CONCLUSIONS: Although an absolute adjustment for the theoretical four factor
      model is not supported by these results, the WHOQoL-Bref is able to discriminate
      the perception of quality of life and the influence of age, gender and disease on
      this perception.

PMID- 24728433
TI  - [Erectile dysfunction among diabetic patients].
AB  - BACKGROUND: Diabetic microangiopathy is one of the main causes of erectile
      dysfunction. AIM: To study the prevalence of erectile dysfunction among diabetic
      patients. MATERIAL AND METHODS: The "international index of erectile function"
      survey was applied to 120 diabetic men aged 21 to 50 years. Demographic data,
      evolution time of diabetes, a glycosilated hemoglobin measured in the last three
      months, weight, height and treatment received were also recorded. RESULTS: Fifty
      five percent of patients had erectile dysfunction. Patients with an inadequate
      metabolic control had a significantly higher risk of having this condition (odds
      ratio 5.5; 95% confidence intervals 2.3-81). CONCLUSIONS: Erectile dysfunction is
      common among diabetic patients and closely associated with an inadequate
      metabolic control.

PMID- 24728434
TI  - [Clinical usefulness of biomarkers in cardiac failure].
AB  - The assessment of patients with a suspected cardiac failure aims to an early and
      precise diagnosis and risk stratification. Only natriuretic peptides have
      demonstrated to be clinically useful. Brain natriuretic peptide stands out due to
      its diagnostic and prognostic value. However its results should be cautiously
      interpreted in the clinical context, bearing in mind possible confounders. The
      combination of markers can provide a better risk stratification and compensates
      the limitations of individual markers. Each new marker gives a new insight on the
      underlying physiopathology of cardiac failure and proposes new therapeutic
      approaches. 

PMID- 24728435
TI  - [Epigenetics in the pathogenesis and early detection of gastric cancer].
AB  - Gastric cancer is the first cause of death for cancer in Chile. The recently
      identified genetic alterations in these tumors have not yielded new biomarkers
      for the disease. Epigenetics or the study of reversible genomic changes that do
      not affect protein codifying DNA sequences but cause phenotypic disturbances, is
      identifying new cancer biomarkers. Specifically, the loss of expression caused by
      the covalent link of a methyl group to carbon 5 of cytosine (DNA
      hypermethylation) is extensively evaluated. Performing an epigenetic evaluation
      of 24 genes, we have identified eight genes associated to the aggressive signet
      ring cell type gastric cancer, the association between APC hypermethylation and
      worse prognosis and BRCA1 hypermethylation association with early onset of
      gastric cancer. The most interesting findings are the hypermethylation of Reprimo
      gene in plasma as a population biomarker and the tissue over expression of p73
      gene (as a consequence of hypomethylation) as a high risk indicator of
      progression to gastric cancer. All these findings are indicating an important
      role of epigenetics in the pathogenesis and early detection of gastric cancer. 

PMID- 24728436
TI  - [The obligation to inform the patient: issues on the right to be informed].
AB  - This article aims to analyze, from a legal perspective, the boundaries of the
      obligation imposed on health care providers to inform the patient. This
      requirement originated and was developed as an ethical issue. However, with the
      newly approved law regulating the rights and duties of patients, the obligation
      to inform can be viewed from prisms and principles that differ from those
      governing medical ethics. With this purpose, we will focus on the comparative
      experience, which will allow us to evaluate the responsibility of health care
      providers when this duty is breached. We will try to answer the following
      questions: Which medical information must be informed to the patient? When should
      the doctor inform the patient? In which form should this information be
      provided?. 

PMID- 24728437
TI  - [The portrait of medicine and Gustav Klimt (1862-1918)].
AB  - Gustav Klimt was an Austrian Symbolist painter and one of the most important
      representatives of the modernist movement of the Viennese Secession. The most
      notable works carried out at his golden age were the "Portrait of Adele Bloch
      Bauer I" and "The kiss". In 1901 he paints "Medicine" where he returns to the
      entanglement of floating bodies -the lifetime- among which appears the skeleton
      of death; a female figure stands out from the column to represent freedom from
      pain. The figure of Hygeia or Hygieia, daughter of Aesculapius, who personifies
      medicine, is shown in the foreground. In 1911, thanks to "The life and death", a
      picture related to medicine, he was awarded the first prize at the Universal
      Exhibition of Rome. A number of his artworks were confiscated by the Nazi
      dictatorship. During the advance of enemy troops, and fearing that these works
      would become spoils of war, it was decided to burn the castle where they remained
      confiscated. Therefore, countless artworks were lost. The progressive development
      of symbolic or abstract motifs already emphasized the freedom of spirit that
      permeated all the avant-garde of early twentieth century. 

PMID- 24728438
TI  - [Metastatic pulmonary calcification in a patient with a functioning kidney
      allograft. Report of one case].
AB  - In renal transplants patients, metastatic pulmonary calcifications have been
      reported occasionally when the grafts are dysfunctional and rarely when they are
      functioning normally. We report a male who received a renal allograft in 1994 at
      the age of 61 years. Nineteen years later a routine chest X ray showed diffuse
      infiltrates and a CT scan showed diffuse calcifications in both lungs. These were
      interpreted as metastatic pulmonary calcifications. The last available laboratory
      determinations were a serum creatinine of 1.4 mg/dl and urinary protein excretion
      of 255 mg/24 hours. No further studies were done since the patient experienced a
      sudden death due to an acute myocardial infarction. 

PMID- 24728439
TI  - [Asymptomatic left ventricular myxoma incidentally diagnosed by echocardiography.
      Report of one case].
AB  - We report a 50 year-old hypertensive and asymptomatic woman in whom a left
      ventricular tumor was found on a routine two-dimensional transthoracic
      echocardiogram. Complementary 3D echocardiography, cardiac magnetic resonance and
      cardiac computed tomography allowed the diagnosis of a calcified left ventricular
      myxoma. Surgical treatment was performed through a transaortic transvalvular
      approach with tumor resection and implantation of a pericardial bovine patch.
      This case confirms the importance of transthoracic echocardiography in the
      diagnosis of cardiac tumors and the complementary role of 3D echocardiography,
      cardiac magnetic resonance imaging and computed tomography for the differential
      diagnosis before surgery. 

PMID- 24728440
TI  - [Cerebral vein thrombosis secondary to closed head injury. Report of one case].
AB  - Intracranial sinus thrombosis (1ST) after closed head injury is an uncommon but
      potentially serious complication. It has no correlation with the severity of the
      injury. The symptoms and clinical course are highly variable. The most frequent
      but least specific symptom is severe headache. Cerebral lesions and neurologic
      signs develop in half of patients with IST. We report a 29 year-old male who had
      an IST after a severe closed head injury. The patient initially developed
      headache and had later 2 secondarily generalized seizures. The magnetic resonance
      imaging showed a superior sagittal sinus thrombosis. Anticoagulation with
      unfractionated heparin and intravenous phenytoin was started. At the moment of
      this report he is asymptomatic and continues with oral anticoagulants and
      phenytoin. 

PMID- 24728441
TI  - [Liraglutide reduces biomarkers and vascular risk in patients with diabetes
      mellitus type 2].

PMID- 24728442
TI  - [To publish our research: what is stopping us?].

PMID- 24728443
TI  - Gas phase dynamics of triplet formation in benzophenone.
AB  - Benzophenone is a prototype molecule for photochemistry in the triplet state
      through its high triplet yield and reactivity. We have investigated its dynamics
      of triplet formation under the isolated gas phase conditions via femtosecond and
      nanosecond time resolved photoelectron spectroscopy. This represents the complete
      evolution from the excitation in S2 to the final decay of T1 to the ground state
      S0. We have found that the triplet formation can be described almost as a direct
      process in preparing T1, the lowest reacting triplet state, from the S1 state
      after S2 -> S1 internal conversion. The molecule was also deposited by a pick-up
      technique on cold argon clusters providing a soft relaxation medium without
      evaporation of the molecule and the mechanism was identical. This cluster
      technique is a model for medium influenced electronic relaxation and provides a
      continuous transition from the isolated gas phase to the relaxation dynamics in
      solution. 

PMID- 24728444
TI  - Coverage of, and compliance with, mass drug administration under the programme to
      eliminate lymphatic filariasis in India: a systematic review.
AB  - India's mass drug administration (MDA) programme to eliminate lymphatic
      filariasis (PELF) covers all 250 endemic districts, but compliance with treatment
      is not adequate for the programme to succeed in eradicating this neglected
      tropical disease. The objective of our study was to systematically review
      published studies on the coverage of and compliance with MDA under the PELF in
      India. We searched several databases-PubMed/Medline, Google Scholar,
      CINAHL/EBSCO, Web of Knowledge (including Web of Science) and OVID-and by
      applying selection criteria identified a total of 36 papers to include in the
      review. Overall MDA coverage rates varied between 48.8% and 98.8%, while
      compliance rates ranged from 20.8% to 93.7%. The coverage-compliance gap is large
      in many MDA programmes. The effective level of compliance, >=65%, was reported in
      only 10 of a total of 31 MDAs (5 of 20 MDAs in rural areas and 2 of 12 MDAs in
      urban areas). The review has identified a gap between coverage and compliance,
      and potentially correctable causes of this gap. These causes need to be addressed
      if the Indian programme is to advance towards elimination of lymphatic
      filariasis. 

PMID- 24728445
TI  - Rising incidence of paediatric inflammatory bowel disease (PIBD) in Wessex,
      Southern England.
AB  - BACKGROUND: There has been a significant increase in the incidence of paediatric
      inflammatory bowel disease (PIBD) over the last 25 years although there is no
      recent data from England. We aimed to analyse changes in incidence within a
      defined English population over the last decade and compare this to recent and
      historical incidence data from comparable studies. METHODS: The new diagnosis
      incidence of PIBD (age less than or equal to 16 years) was recorded from a
      prospective database for a geographically defined area within Southern England
      (2002-2012). Data were analysed for two separate time periods (cohort 1:2002-2006
      and cohort 2:2008-2012) and compared to data from the British Paediatric
      Surveillance Unit (BPSU) survey in 1998/1999. Data were analysed by age, sex and
      disease type. RESULTS: There has been an increase in incidence of PIBD from
      6.39/100,000/year during cohort 1 to 9.37/100,000/year during cohort 2
      (p=0.0002). This compares with the BPSU incidence data in England (1998-1999) of
      5.2/100,000/year. There was no statistically significant difference in median age
      of diagnosis between cohorts (p=0.46). The incidence of Crohn's disease (CD) was
      3.8/100,000/year in cohort 1 rising to 5.85/100,000/year in cohort 2 (p=0.001).
      The incidence of ulcerative colitis (UC) was 2.01/100,000/year in cohort 1 rising
      to 2.62/100,000/year in cohort 2 (p=0.1458). Overall PIBD incidence is higher in
      males in cohort 1 (male-to-female ratio 1.35:1) and cohort 2 (male-to-female
      ratio 1.5:1). CONCLUSIONS: The incidence of PIBD continues to increase with a
      rise of almost 50% in the last decade in Southern England. The reasons for this
      increase remain unclear.

PMID- 24728446
TI  - Familial haematuria: when to consider genetic testing.
AB  - Haematuria is a common finding in children. It is important to identify the
      underlying cause whenever possible so that appropriate follow-up is organised,
      particularly if the child is at risk of developing renal impairment or renal
      failure in later life. Until recently nephrologists relied on renal biopsy with
      examination under the electron microscope to make a diagnosis, but genetic
      testing can often provide an answer, together with additional information about
      the pattern of inheritance, which is also useful for other family members. 

PMID- 24728447
TI  - Identifying visual difficulty in children with special educational needs: where
      should we look?

PMID- 24728448
TI  - Low incidence of chest wall pain with a risk-adapted lung stereotactic body
      radiation therapy approach using three or five fractions based on chest wall
      dosimetry.
AB  - PURPOSE: To examine the frequency and potential of dose-volume predictors for
      chest wall (CW) toxicity (pain and/or rib fracture) for patients receiving lung
      stereotactic body radiotherapy (SBRT) using treatment planning methods to
      minimize CW dose and a risk-adapted fractionation scheme. METHODS: We reviewed
      data from 72 treatment plans, from 69 lung SBRT patients with at least one year
      of follow-up or CW toxicity, who were treated at our center between 2010 and
      2013. Treatment plans were optimized to reduce CW dose and patients received a
      risk-adapted fractionation of 18 Gy*3 fractions (54 Gy total) if the CW V30 was
      less than 30 mL or 10-12 Gy*5 fractions (50-60 Gy total) otherwise. The
      association between CW toxicity and patient characteristics, treatment parameters
      and dose metrics, including biologically equivalent dose, were analyzed using
      logistic regression. RESULTS: With a median follow-up of 20 months, 6 (8.3%)
      patients developed CW pain including three (4.2%) grade 1, two (2.8%) grade 2 and
      one (1.4%) grade 3. Five (6.9%) patients developed rib fractures, one of which
      was symptomatic. No significant associations between CW toxicity and patient and
      dosimetric variables were identified on univariate nor multivariate analysis.
      CONCLUSIONS: Optimization of treatment plans to reduce CW dose and a risk-adapted
      fractionation strategy of three or five fractions based on the CW V30 resulted in
      a low incidence of CW toxicity. Under these conditions, none of the patient
      characteristics or dose metrics we examined appeared to be predictive of CW pain.

PMID- 24728453
TI  - PDZK1 and NHERF1 regulate the function of human organic anion transporting
      polypeptide 1A2 (OATP1A2) by modulating its subcellular trafficking and
      stability.
AB  - The human organic anion transporting polypeptide 1A2 (OATP1A2) is an important
      membrane protein that mediates the cellular influx of various substances
      including drugs. Previous studies have shown that PDZ-domain containing proteins,
      especially PDZK1 and NHERF1, regulate the function of related membrane
      transporters in other mammalian species. This study investigated the role of
      PDZK1 and NHERF1 in the regulation of OATP1A2 in an in vitro cell model.
      Transporter function and protein expression were assessed in OATP1A2-transfected
      HEK-293 cells that co-expressed PDZK1 or NHERF1. Substrate (estrone-3-sulfate)
      uptake by OATP1A2 was significantly increased to ~1.6- (PDZK1) and ~1.8- (NHERF1)
      fold of control; this was dependent on the putative PDZ-binding domain within the
      C-terminus of OATP1A2. The functional increase of OATP1A2 following PDZK1 or
      NHERF1 over-expression was associated with increased transporter expression at
      the plasma membrane and in the whole cell, and was reflected by an increase in
      the apparent maximal velocity of estrone-3-sulfate uptake (V(max): 138.9+/-4.1
      (PDZK1) and 181.4+/-16.7 (NHERF1) versus 55.5+/-3.2 pmol*(ug*4 min)-1 in control;
      P<0.01). Co-immunoprecipitation analysis indicated that the regulatory actions of
      PDZK1 and NHERF1 were mediated by direct interaction with OATP1A2 protein. In
      further experiments PDZK1 and NHERF1 modulated OATP1A2 expression by decreasing
      its internalization in a clathrin-dependent (but caveolin-independent) manner.
      Additionally, PDZK1 and NHERF1 enhanced the stability of OATP1A2 protein in HEK
      293 cells. The present findings indicated that PDZK1 and NHERF1 regulate the
      transport function of OATP1A2 by modulating protein internalization via a
      clathrin-dependent pathway and by enhancing protein stability.

PMID- 24728454
TI  - Efficient route to high-bandwidth nanoscale magnetometry using single spins in
      diamond.
AB  - Nitrogen-vacancy (NV) center in diamond is a promising quantum metrology tool
      finding applications across disciplines. The spin sensor measures magnetic
      fields, electric fields and temperature with nano-scale precision and is fully
      operable under ambient conditions. Moreover, it achieves precision scaling
      inversely with total measurement time sigmaB ? 1/T (Heisenberg scaling) rather
      than as the inverse of the square root of T, with sigmaB = ?T the Shot-Noise
      limit. This scaling can be achieved by means of phase estimation algorithms
      (PEAs), in combination with single-shot read-out. Despite their accuracy, the
      range of applicability of PEAs is limited to sensing single frequencies with
      negligible temporal fluctuations. Nuclear Magnetic Resonance (NMR) signals from
      molecules often contain multifrequency components and sensing them using PEA is
      ruled out. Here we propose an alternative method for precision magnetometry in
      frequency multiplexed signals via compressive sensing (CS) techniques focusing on
      nanoscale NMR. We show that CS can provide for precision scaling approximately as
      sigmaB ~ 1/T, as well as for a 5-fold increase in sensitivity over dynamic-range
      gain, in addition to reducing the total number of resources required. We
      illustrate our method by taking model solid-state spectra of Glycine acquired
      under Magic Angle Spinning conditions.

PMID- 24728455
TI  - Effect of HDL-raising drugs on cardiovascular outcomes: a systematic review and
      meta-regression.
AB  - BACKGROUND: Substantial residual cardiovascular risk remains after optimal LDL
      lowering in patients of established coronary artery disease. A number of
      therapeutic agents that raise HDL-C have been tested in clinical trials to cover
      this risk. However, the results of clinical trials are conflicting. OBJECTIVES:
      To determine whether raising HDL-C with pharmacologic therapies translates into
      beneficial cardiovascular outcomes and to find out if this change was
      proportional to the percentage change in HDL levels. METHODS: Electronic and
      printed sources were searched up to August, 2013 for randomised controlled trials
      (RCTs) using at least one of the HDL raising therapies for secondary prevention
      of adverse cardiovascular events over optimal LDL levels. Data from eligible
      studies were pooled for the following outcomes: all cause mortality,
      cardiovascular disease mortality, hospitalization for unstable angina, non-fatal
      myocardial infarction, coronary revascularization and ischemic stroke. Mantel
      Haensnzel fixed effect model was used preferentially. Meta-regression was done to
      see the correlation of change in HDL levels and cardiovascular outcomes. Pooled
      odds ratios with 95% confidence interval (CI) were calculated. RESULTS: A total
      of 12 RCTs including 26,858 patients with follow up period ranging from 1 year to
      6.2 years were included in the analysis. Pooled analysis showed no significant
      difference in all-cause mortality between the treatment and control group (Pooled
      OR 1.07; 95% CI 0.98-1.16, p = 0.15). No significant difference was found between
      the groups for any of the secondary outcomes. Similarly no correlation was seen
      between percentage change in HDL and adverse cardiovascular outcomes on meta
      regression analysis. CONCLUSION: Increasing HDL levels via pharmacological
      manipulation beyond optimal lipid lowering therapy for secondary prevention is
      not beneficial.

PMID- 24728462
TI  - Combinatorial development of bulk metallic glasses.
AB  - The identification of multicomponent alloys out of a vast compositional space is
      a daunting task, especially for bulk metallic glasses composed of three or more
      elements. Despite an increasing theoretical understanding of glass formation,
      bulk metallic glasses are predominantly developed through a sequential and time
      consuming trial-and-error approach. Even for binary systems, accurate quantum
      mechanical approaches are still many orders of magnitude away from being able to
      simulate the relatively slow kinetics of glass formation. Here, we present a high
      throughput strategy where ~3,000 alloy compositions are fabricated simultaneously
      and characterized for thermoplastic formability through parallel blow forming.
      Using this approach, we identified the composition with the highest thermoplastic
      formability in the glass-forming system Mg-Cu-Y. The method provides a versatile
      toolbox for unveiling complex correlations of material properties and glass
      formation, and should facilitate a drastic increase in the discovery rate of
      metallic glasses. 

PMID- 24728463
TI  - Vacancy defects and monopole dynamics in oxygen-deficient pyrochlores.
AB  - The idea of magnetic monopoles in spin ice has enjoyed much success at
      intermediate temperatures, but at low temperatures a description in terms of
      monopole dynamics alone is insufficient. Recently, numerical simulations were
      used to argue that magnetic impurities account for this discrepancy by
      introducing a magnetic equivalent of residual resistance in the system. Here we
      propose that oxygen deficiency is the leading cause of magnetic impurities in as
      grown samples, and we determine the defect structure and magnetism in Y2Ti2O7
      delta using diffuse neutron scattering and magnetization measurements. These
      defects are eliminated by oxygen annealing. The introduction of oxygen vacancies
      causes Ti(4+) to transform to magnetic Ti(3+) with quenched orbital magnetism,
      but the concentration is anomalously low. In the spin-ice material Dy2Ti2O7 we
      find that the same oxygen-vacancy defects suppress moments on neighbouring rare
      earth sites, and that these magnetic distortions markedly slow down the long-time
      monopole dynamics at sub-Kelvin temperatures. 

PMID- 24728461
TI  - Hippo/YAP-mediated rigidity-dependent motor neuron differentiation of human
      pluripotent stem cells.
AB  - Our understanding of the intrinsic mechanosensitive properties of human
      pluripotent stem cells (hPSCs), in particular the effects that the physical
      microenvironment has on their differentiation, remains elusive. Here, we show
      that neural induction and caudalization of hPSCs can be accelerated by using a
      synthetic microengineered substrate system consisting of poly(dimethylsiloxane)
      micropost arrays (PMAs) with tunable mechanical rigidities. The purity and yield
      of functional motor neurons derived from hPSCs within 23 days of culture using
      soft PMAs were improved more than fourfold and tenfold, respectively, compared
      with coverslips or rigid PMAs. Mechanistic studies revealed a multi-targeted
      mechanotransductive process involving Smad phosphorylation and nucleocytoplasmic
      shuttling, regulated by rigidity-dependent Hippo/YAP activities and actomyosin
      cytoskeleton integrity and contractility. Our findings suggest that substrate
      rigidity is an important biophysical cue influencing neural induction and subtype
      specification, and that microengineered substrates can thus serve as a promising
      platform for large-scale culture of hPSCs. 

PMID- 24728464
TI  - Universal process-inert encoding architecture for polymer microparticles.
AB  - Polymer microparticles with unique, decodable identities are versatile
      information carriers with a small footprint. Widespread incorporation into
      industrial processes, however, is limited by a trade-off between encoding
      density, scalability and decoding robustness in diverse physicochemical
      environments. Here, we report an encoding strategy that combines spatial
      patterning with rare-earth upconversion nanocrystals, single-wavelength near
      infrared excitation and portable CCD (charge-coupled device)-based decoding to
      distinguish particles synthesized by means of flow lithography. This architecture
      exhibits large, exponentially scalable encoding capacities (>10(6) particles), an
      ultralow decoding false-alarm rate (<10(-9)), the ability to manipulate particles
      by applying magnetic fields, and pronounced insensitivity to both particle
      chemistry and harsh processing conditions. We demonstrate quantitative agreement
      between observed and predicted decoding for a range of practical applications
      with orthogonal requirements, including covert multiparticle barcoding of
      pharmaceutical packaging (refractive-index matching), multiplexed microRNA
      detection (biocompatibility) and embedded labelling of high-temperature-cast
      objects (temperature resistance). 

PMID- 24728465
TI  - Heterozygote loss of ACE2 is sufficient to increase the susceptibility to heart
      disease.
AB  - Angiotensin-converting enzyme 2 (ACE2) metabolizes Ang II into Ang 1-7 thereby
      negatively regulating the renin-angiotensin system. However, heart disease in
      humans and in animal models is associated with only a partial loss of ACE2. ACE2
      is an X-linked gene; and as such, we tested the clinical relevance of a partial
      loss of ACE2 by using female ACE2(+/+) (wildtype) and ACE2(+/-) (heterozygote)
      mice. Pressure overload in ACE2(+/-) mice resulted in greater LV dilation and
      worsening systolic and diastolic dysfunction. These changes were associated with
      increased myocardial fibrosis, hypertrophy, and upregulation of pathological gene
      expression. In response to Ang II infusion, there was increased NADPH oxidase
      activity and myocardial fibrosis resulting in the worsening of Ang II-induced
      diastolic dysfunction with a preserved systolic function. Ang II-mediated
      cellular effects in cultured adult ACE2(+/-) cardiomyocytes and cardiofibroblasts
      were exacerbated. Ang II-mediated pathological signaling worsened in ACE2(+/-)
      hearts characterized by an increase in the phosphorylation of ERK1/2 and JNK1/2
      and STAT-3 pathways. The ACE2(+/-) mice showed an exacerbated pressor response
      with increased vascular fibrosis and stiffness. Vascular superoxide and
      nitrotyrosine levels were increased in ACE2(+/-) vessels consistent with
      increased vascular oxidative stress. These changes occurred with increased renal
      fibrosis and superoxide production. Partial heterozygote loss of ACE2 is
      sufficient to increase the susceptibility to heart disease secondary to pressure
      overload and Ang II infusion. KEY MESSAGE: Heart disease in humans with
      idiopathic dilated cardiomyopathy is associated with a partial loss of ACE2.
      Heterozygote female ACE2 mutant mice showed enhanced susceptibility to pressure
      overload-induced heart disease. Heterozygote female ACE2 mutant mice showed
      enhanced susceptibility to Ang II-induced heart and vascular diseases. Partial
      loss of ACE2 is sufficient to enhance the susceptibility to heart disease.

PMID- 24728468
TI  - Proposal for a modification of the UVI risk scale.
AB  - The standardisation of UV information to the public through the UV Index (UVI)
      has been hugely beneficial since its endorsement by multiple international
      agencies more than 10 years ago. It has now gained widespread acceptance, and UVI
      values are available throughout the world from satellite instruments, ground
      based measurements, and from forecasts based on model calculations. These have
      been useful for atmospheric scientists, health professionals (skin and eye
      specialists), and the general public. But the descriptors and health messages
      associated with the UVI scale are targeted towards European skin types and UV
      regimes, and are not directly applicable to the population living closer to the
      equator, especially for those in the high-altitude Altiplano region of South
      America. This document arose from discussions at the Latin American Society of
      Photobiology and Photomedicine's Congress, which was held in Arequipa, Peru, in
      November 2013. A major outcome of the meeting was the Arequipa Accord, which is
      intended as a unifying document to ensure co-ordination of UV and health research
      decisions in Latin America. A plank of that agreement was the need to tailor the
      UVI scale to make it more relevant to the region and its population. Here we make
      some suggestions to improve the international applicability of the UVI scale. 

PMID- 24728466
TI  - Blockade of the VEGF isoforms in inflammatory corneal hemangiogenesis and
      lymphangiogenesis.
AB  - BACKGROUND: The VEGF-A family plays a crucial role in the induction of
      pathological corneal neovascularization. The role of the different VEGF-A
      isoforms during lymphangiogenesis is only little-known. Current anti-angiogenic
      therapies in the eye and other organs inhibit all VEGF-A isoforms, and have
      effects on both blood and lymphatic vessels. Here we investigate whether
      selective targeting of the isoform VEGF 165 is able to inhibit corneal
      lymphangiogenesis under inflammatory conditions. METHODS: The mouse model of
      suture-induced corneal neovascularization was used to assess the antihem- and
      antilymphangiogenic effect of topically applied pegaptanib. Corneal blood and
      lymph vascularized areas were analyzed morphometrically. Furthermore, we analyzed
      the proliferative effects of VEGF A 121, 165, and 189 on blood and lymphatic
      endothelial cells (BEC/LEC) via a cell-proliferation assay. RESULTS: Pegaptanib
      significantly inhibited inflammatory corneal hemangiogenesis (p < 0.01), but not
      lymphangiogenesis in vivo (p > 0.05), both topically as well as systemically, in
      the inflamed cornea. In vitro, BECs were more susceptible to pegaptanib than
      LECs. CONCLUSIONS: Targeting VEGF-A 165 significantly inhibits hem- but not
      lymphangiogenesis, suggesting VEGF-A 165 to be critical for hem-, but dispensable
      for lymphangiogenesis, at least in the inflamed cornea.

PMID- 24728467
TI  - Efficacy and feasibility of cyclophosphamide combined with intermediate- dose or
      high-dose cytarabine for relapsed and refractory acute myeloid leukemia (AML).
AB  - BACKGROUND: Approximately, 70 % of adult patients with de novo acute myeloid
      leukemia (AML) achieve a complete remission (CR) while 10-20 % of AML are
      refractory to induction chemotherapy. Furthermore, a significant proportion of
      AML patients in CR will relapse during or after consolidation treatment. There is
      no evidence for a standard salvage regimen and most centers use a combination of
      an anthracycline and cytarabine (AraC). The aim of this study was to investigate
      the impact of two age-adjusted regimens containing AraC and cyclophosphamide
      applied for the treatment of relapsed or refractory AML. PATIENTS AND METHODS: We
      retrospectively analyzed 60 patients (24 male, 36 female; median age 56 years)
      with relapsed or refractory AML who were treated with a combination of AraC and
      cyclophosphamide monocentrically between October 2000 and January 2013. Two
      different protocols containing either high-dose (hAC) or intermediate-dose
      cytarabin (iAC) have been applied dependent on age and performance status.
      RESULTS: We demonstrate an overall response rate (CR + PR) induced by hAC and iAC
      of 56.7 %. Importantly, a complete remission rate (CR + CRp) of 52.2 % was found
      in patients who received the hAC regimen while only 8.8 % of patients achieved a
      CR following the iAC protocol (p < 0.001). The rate of refractory disease was
      26.1 and 47.1 %, respectively. High-risk cytogenetics, i.e., a complex aberrant
      or monosomal karyotype had no effect on achievement of CR after hAC. In addition,
      there was no impact of activating FLT3 mutations on response to treatment
      according to the hAC regimen. In the cohort of patients treated with the iAC
      protocol, treatment-related mortality of 11.8 % within 60 days was observed but
      none of the patients who received the hAC regimen died within the first 2 months
      following chemotherapy. The toxicity profile was acceptable at both cytarabine
      dose levels. Importantly, 19 patients (82.6 %) of the hAC cohort underwent
      allogeneic hematopoietic stem cell transplantation (HSCT) as consecutive
      treatment. CONCLUSION: The hAC regimen represents a promising therapeutic
      approach to induce a second CR in younger patients with relapsed or refractory
      AML prior to HSCT without using anthracyclines.

PMID- 24728469
TI  - Zebularine induces prolonged apoptosis effects via the caspase-3/PARP pathway in
      head and neck cancer cells.
AB  - Zebularine, a potent DNA methyltransferase inhibitor, is potentially able to
      influence gene regulation and thereby alters cell behavior. This study
      illustrates the effect of zebularine on human squamous cell carcinoma (SCC-9 and
      SCC-25) in vitro. The results indicated that zebularine significantly (P<0.05)
      reduced viability and DNA synthesis of treated cancer cells, by induction of cell
      cycle arrest at G2/M phase and apoptosis in both tested cell lines. This effect
      was confirmed to be mediated through p21/CHK1- and caspase 3/PARP-dependent
      pathways, respectively. However, no methylation was observed in the promoter
      region of the upregulated p21 and CHK1 genes. This may indicate that the
      alteration of p21 and CHK1 following zebularine administration was not due to
      inhibition of methylation of their promoter. Interestingly, it was observed that
      zebularine continued to influence cell viability for a week following its
      withdrawal. This may indicate feasibility of novel drug administration
      strategies, in which, daily administration of the drug replaced by weekly use,
      leading to improved therapeutic process and cost-effectiveness of the treatment
      in head and neck cancer. 

PMID- 24728470
TI  - Prevalence of HCV infection and associated factors among illicit drug users in
      Breves, State of Para, northern Brazil.
AB  - INTRODUCTION: Illicit drug users (DUs) are vulnerable to hepatitis C virus (HCV)
      infection. The shared use of illicit drugs is the main method of HCV
      transmission. METHODS: A cross-sectional study was conducted in Breves, in
      northern Brazil. We surveyed 187 DUs to determine the prevalence of and factors
      associated with HCV infection. RESULTS: The prevalence of anti-HCV antibodies was
      36.9%, and the prevalence of hepatitis C virus-ribonucleic acid (HCV-RNA) was
      31%. Hepatitis C virus infection was associated with tattoos, intravenous drug
      use, shared use of equipment for drug use, drug use for longer than 3 years, and
      daily drug use. CONCLUSIONS: Strategies for preventing and controlling HCV
      transmission should be implemented among DUs.

PMID- 24728471
TI  - First report of Rhodnius montenegrensis (Hemiptera: Reduviidae: Triatominae)
      infection by Trypanosoma rangeli.
AB  - INTRODUCTION: This study reports for the first time the infection of Rhodnius
      montenegrensis by Trypanosoma rangeli. METHODS: The triatomines were manually
      collected in Attalea speciosa in the municipality of Buritis, Rondonia. The
      identification of the trypanosomatid species was confirmed by multiplex PCR.
      RESULTS: All of the collected triatomines were R. montenegrensis. The analysis
      confirmed that all of the adults were infected with the epimastigote form of T.
      rangeli. CONCLUSIONS: This report of a new vector of T. rangeli raises a warning
      for the State of Rondonia because the simultaneous presence of T. rangeli with T.
      cruzi in the same geographic region enables the occurrence of mixed infections in
      hosts and vectors, which complicates the differential diagnosis.

PMID- 24728472
TI  - Growth in children with chronic kidney disease: a report from the Chronic Kidney
      Disease in Children Study.
AB  - BACKGROUND: Growth failure is common among children with chronic kidney disease
      (CKD). We examined the relationship of growth parameters with glomerular
      filtration rate (GFR), CKD diagnosis, sex and laboratory results in children with
      CKD. METHODS: Baseline data from 799 children (median age 11.0 years, median GFR
      49.9 mL/min/1.73 m(2)) participating in the Chronic Kidney Disease in Children
      Study were examined. Growth was quantified by age-sex-specific height, weight,
      body mass index (BMI-age), and height-age-sex-specific BMI (BMI-height-age)
      standard deviation scores (SDS). RESULTS: Median height and weight SDS were -0.55
      [interquartile range (IQR) -1.35 to 0.19] and 0.03 (IQR -0.82 to 0.97),
      respectively. Girls with non-glomerular CKD were the shortest (median height SDS 
      0.83; IQR -1.62 to -0.02). Compared to those with a serum bicarbonate (CO2) level
      of >= 22 mEq/L, children with CO2 of <18 mEq/L had a height SDS that was on
      average 0.67 lower [95 % confidence interval (CI) -0.31 to -1.03]. Only 23 % of
      children with a height SDS of <=-1.88 were prescribed growth hormone therapy.
      Forty-six percent of children with glomerular CKD were overweight or obese (BMI
      height-age >= 85th percentile). CONCLUSIONS: Growth outcomes in a contemporary
      cohort of children with CKD remain suboptimal. Interventions targeting metabolic
      acidosis and overcoming barriers to recombinant human growth hormone usage may
      improve growth in this population.

PMID- 24728473
TI  - Renal sonography with Doppler - not shown to be adequate as a screening tool for
      renovascular hypertension.

PMID- 24728474
TI  - Reply to Drs. Brown and Karmazyn regarding the adequacy of renal sonography with
      Doppler in pediatric renovascular hypertension.

PMID- 24728475
TI  - The molecular configuration of a DOPA/ST monolayer at the air-water interface: a
      molecular dynamics study.
AB  - In this study, surface pressure-area isotherms for N-stearoyldopamine (DOPA) and
      4-stearylcatechol (ST) monolayers are obtained by means of molecular dynamics
      simulations and compared to experimental isotherms. The difference between DOPA
      and ST is an amide group, which is present in the alkyl tails of DOPA molecules.
      We find a large difference between the isotherms for DOPA and ST monolayers. Upon
      using TIP4P/2005 for water and OPLS force fields for the organic material and a
      relatively large system size, the simulated results are found to be consistent
      with experiments. With molecular dynamics simulations, the configurations of
      molecules in the monolayers can be directly analyzed. When the surface pressure
      is high, a regular molecular orientation is observed for ST molecules, whereas
      regular orientations are only observed in local domains for DOPA molecules. The
      differences between DOPA and ST monolayers are attributed to the amide groups in
      DOPA molecules, which are useful for both steric effects and the formation of
      hydrogen bonds in the DOPA monolayers. This study clearly demonstrates that
      hydrogen bonds, due to the presence of the amide group in DOPA, are the cause of
      the disorder in its Langmuir monolayers. Thus, the conclusion may be helpful in
      making ordered organic monolayers in the future. 

PMID- 24728476
TI  - Controlling nucleation in giant liposomes.
AB  - We introduce giant liposomes to investigate phase transformations in picoliter
      volumes. Precipitation of calcium carbonate in the confinement of DPPC liposomes
      leads to dramatic stabilization of amorphous calcium carbonate (ACC). In
      contrast, amorphous strontium carbonate (ASC) is a transient species, and BaCO3
      precipitation leads directly to the formation of crystalline witherite. 

PMID- 24728477
TI  - The relationship between total bilirubin levels and total mortality in older
      adults: the United States National Health and Nutrition Examination Survey
      (NHANES) 1999-2004.
AB  - OBJECTIVE: Due to its anti-oxidant and anti-inflammatory properties, bilirubin
      has been associated with reduced cardiovascular risk. A recent study demonstrated
      an L-shaped association of pre-treatment total bilirubin levels with total
      mortality in a statin-treated cohort. We therefore investigated the association
      of total bilirubin levels with total mortality in a nationally representative
      sample of older adults from the general population. METHODS: A total of 4,303
      participants aged >= 60 years from the United States National Health and
      Nutrition Examination Survey 1999-2004 with mortality data followed up through
      December 31, 2006 were included in this analysis, with a mean follow-up period of
      4.5 years. RESULTS: Participants with total bilirubin levels of 0.1-0.4 mg/dl had
      the highest mortality rate (19.8%). Compared with participants with total
      bilirubin levels of 0.5-0.7 mg/dl and in a multivariable regression model, a
      lower total bilirubin level of 0.1-0.4 mg/dl was associated with higher risk of
      total mortality (hazard ratios, 1.36; 95% confidence interval, 1.07-1.72; P =
      0.012), while higher levels (>= 0.8 mg/dl) also tended to be associated with
      higher risk of total mortality, but this did not reach statistical significance
      (hazard ratios, 1.24; 95% confidence interval, 0.98-1.56; P = 0.072). CONCLUSION:
      In this nationally representative sample of older adults, the association of
      total bilirubin levels with total mortality was the highest among those with a
      level between 0.1 and 0.4 mg/dl. Further studies are needed to investigate
      whether higher total bilirubin levels could be associated with a higher mortality
      risk, compared to a level of 0.5-0.7 mg/dl.

PMID- 24728478
TI  - A unique 1-amino-1-cyclopropane carboxylate cupric-cryptate hosting sodium.
AB  - The first cluster containing acc was prepared via supramolecular self-assembly.
      This Cu(II) cluster traps Na(+), as shown in the solid state by the crystal
      structure and in solution by ESI-MS. Further characterisations revealed a
      ferromagnetic intracluster exchange and an irreversible reduction with a rapid
      intracluster electron transfer.

PMID- 24728479
TI  - Whole-genome sequencing of Berkshire (European native pig) provides insights into
      its origin and domestication.
AB  - Domesticated organisms have experienced strong selective pressures directed at
      genes or genomic regions controlling traits of biological, agricultural or
      medical importance. The genome of native and domesticated pigs provide a unique
      opportunity for tracing the history of domestication and identifying signatures
      of artificial selection. Here we used whole-genome sequencing to explore the
      genetic relationships among the European native pig Berkshire and breeds that are
      distributed worldwide, and to identify genomic footprints left by selection
      during the domestication of Berkshire. Numerous nonsynonymous SNPs-containing
      genes fall into olfactory-related categories, which are part of a rapidly
      evolving superfamily in the mammalian genome. Phylogenetic analyses revealed a
      deep phylogenetic split between European and Asian pigs rather than between
      domestic and wild pigs. Admixture analysis exhibited higher portion of Chinese
      genetic material for the Berkshire pigs, which is consistent with the historical
      record regarding its origin. Selective sweep analyses revealed strong signatures
      of selection affecting genomic regions that harbor genes underlying economic
      traits such as disease resistance, pork yield, fertility, tameness and body
      length. These discoveries confirmed the history of origin of Berkshire pig by
      genome-wide analysis and illustrate how domestication has shaped the patterns of
      genetic variation. 

PMID- 24728481
TI  - Public health leadership and electronic cigarette users.

PMID- 24728480
TI  - Lower transplacental antibody transport for measles, mumps, rubella and varicella
      zoster in very preterm infants.
AB  - BACKGROUND: Maternal antibodies, transported over the placenta during pregnancy,
      contribute to the protection of infants from infectious diseases during the first
      months of life. In term infants, this protection does not last until the first
      recommended measles-mumps-rubella vaccination at 14 months in the Netherlands,
      while these viruses still circulate. The aim of the study was to investigate the
      antibody concentration against measles, mumps, rubella and varicella (MMRV) in
      mothers and preterm infants or healthy term infants at birth. METHODS: Antibody
      concentrations specific for MMRV were measured in cord blood samples from preterm
      (gestational age <32 weeks and/or birth weight <1500 g) and term infants, and
      matched maternal serum samples, using a fluorescent bead-based multiplex immune
      assay. RESULTS: Due to lower placental transfer ratios of antibodies against MMRV
      in 96 preterm infants (range 0.75-0.87) compared to 42 term infants (range 1.39
      1.65), the preterm infants showed 1.7-2.5 times lower geometric mean
      concentrations at birth compared to term infants. Maternal antibody concentration
      is the most important determinant of infant antibody concentration against MMRV.
      CONCLUSIONS: Preterm infants benefit to a lesser extent from maternal antibodies
      against measles, mumps, rubella and varicella than term infants, posing them even
      earlier at risk for infectious diseases caused by these still circulating
      viruses.

PMID- 24728482
TI  - A new era of therapeutic strategies for chronic thromboembolic pulmonary
      hypertension by two different interventional therapies; pulmonary endarterectomy
      and percutaneous transluminal pulmonary angioplasty.
AB  - BACKGROUND: Pulmonary endarterectomy (PEA) is established for the treatment of
      chronic thromboembolic pulmonary hypertension (CTEPH). Recently, percutaneous
      transluminal pulmonary angioplasty (PTPA) has been added for peripheral-type
      CTEPH, whose lesions exist in segmental, subsegmental, and more distal pulmonary
      arteries. A shift in clinical practice of interventional therapies occurred in
      2009 (first mainly PEA, later PTPA). We examined the latest clinical outcomes of
      patients with CTEPH. METHODS AND RESULTS: This study retrospectively included 136
      patients with CTEPH. Twenty-nine were treated only with drug (Drug-group), and
      the other 107 underwent interventional therapies (Interventions-group) (39
      underwent PEA [PEA-group] and 68 underwent PTPA [PTPA-group]). Total 213 PTPA
      sessions (failures, 0%; mortality rate, 1.47%) was performed in the PTPA-group
      (complications: reperfusion pulmonary edema, 7.0%; hemosputum or hemoptysis,
      5.6%; vessel dissection, 2.3%; wiring perforation, 0.9%). Although baseline
      hemodynamic parameters were significantly more severe in the Interventions-group,
      the outcome after the diagnosis was much better in the Interventions-group than
      in the Drug-group (98% vs. 64% 5-year survival, p<0.0001). Hemodynamic
      improvement in the PEA-group was a 46% decrease in mean pulmonary arterial
      pressure (PAP) and a 49% decrease in total pulmonary resistance (TPR) (follow-up
      period; 74.7 +/- 32.3 months), while those in the PTPA-group were a 40% decrease
      in mean PAP and a 49% decrease in TPR (follow-up period; 17.4 +/- 9.3 months).
      The 2-year survival rate in the Drug-group was 82.0%, and the 2-year survival
      rate, occurrence of right heart failure, and re-vascularization rate in the PEA
      group were 97.4%, 2.6%, and 2.8%, and those in the PTPA-group were 98.5%, 2.9%,
      and 2.9%, respectively. CONCLUSION: The patients who underwent interventional
      therapies had better results than those treated only with drugs. The availability
      of both of these operative and catheter-based interventional therapies leads us
      to expect the dawn of a new era of therapeutic strategies for CTEPH.

PMID- 24728485
TI  - Major clinical features of synostotic occipital plagiocephaly: mechanisms of
      cranial deformations.
AB  - PURPOSE: The clinical diagnosis of most common single-suture craniosynostosis is
      easily set, based on the stereotype of deformities and knowledge of the
      mechanisms of cranial deformations. However, synostosis of unilateral lambdoid
      suture, probably due to its lower incidence and similarity with other non
      synostotic deformities affecting the posterior portion of the skull, makes its
      clinical diagnosis more difficult and imprecise. The aim of this study is to
      evaluate the most easily and accurate clinical characteristics to be recognized
      in the synostotic occipital plagiocephaly. METHODS: This study consisted of
      clinical evaluation of eight patients with synostotic occipital plagiocephaly,
      whose diagnosis was further corroborated by computed tomography. RESULTS: We
      identified the following: unilateral occipital flattening in eight out of eight
      patients (100 %), bulging of ipsilateral mastoid process in eight out of eight
      (100 %), "edge effect" of ipsilateral lambdoid suture in eight out of eight (100
      %), inferior deviation of the ear in eight out of eight (100 %), "Dumbo" ears in
      eight out of eight (100 %), horizontal slant of the bimastoid line in seven out
      of eight (87.5 %), tilt of the head viewed from behind in seven out of eight
      (87.5 %), trapezoidal contour of the skull in top view in six out of eight (75
      %), contralateral parietal bossing in six out of eight (75 %), and bossing of the
      contralateral forehead three out of eight (37.5 %). CONCLUSIONS: The most
      important clinical features specific to the clinical diagnosis of synostotic
      occipital plagiocephaly, not present in the positional posterior plagiocephaly,
      were bulging of the ipsilateral mastoid process, edge effect of the synostotic
      lambdoid suture, tilt of the head, and slant of the bimastoid line viewed from
      behind, inferior deviation of the ear, and contralateral parietal bossing.

PMID- 24728486
TI  - pH-triggered formation of nanoribbons from yeast-derived glycolipid
      biosurfactants.
AB  - In the present paper, we show that the saturated form of acidic sophorolipids, a
      family of industrially scaled bolaform microbial glycolipids, unexpectedly forms
      chiral nanofibers only at pH below 7.5. In particular, we illustrate that this
      phenomenon derives from a subtle cooperative effect of molecular chirality,
      hydrogen bonding, van der Waals forces and steric hindrance. The pH-responsive
      behaviour was shown by Dynamic Light Scattering (DLS), pH-titration and Field
      Emission Scanning Electron Microscopy (FE-SEM) while the nanoscale chirality was
      evidenced by Circular Dichroism (CD) and cryo Transmission Electron Microscopy
      (cryo-TEM). The packing of sophorolipids within the ribbons was studied using
      Small Angle Neutron Scattering (SANS), Wide Angle X-ray Scattering (WAXS) and 2D
      (1)H-(1)H through-space correlations via Nuclear Magnetic Resonance under very
      fast (67 kHz) Magic Angle Spinning (MAS-NMR). 

PMID- 24728487
TI  - Mapping ecological processes and ecosystem services for prioritizing restoration
      efforts in a semi-arid Mediterranean river basin.
AB  - Semi-arid Mediterranean regions are highly susceptible to desertification
      processes which can reduce the benefits that people obtain from healthy
      ecosystems and thus threaten human wellbeing. The European Union Biodiversity
      Strategy to 2020 recognizes the need to incorporate ecosystem services into land
      use management, conservation, and restoration actions. The inclusion of ecosystem
      services into restoration actions and plans is an emerging area of research, and
      there are few documented approaches and guidelines on how to undertake such an
      exercise. This paper responds to this need, and we demonstrate an approach for
      identifying both key ecosystem services provisioning areas and the spatial
      relationship between ecological processes and services. A degraded semi-arid
      Mediterranean river basin in north east Spain was used as a case study area. We
      show that the quantification and mapping of services are the first step required
      for both optimizing and targeting of specific local areas for restoration.
      Additionally, we provide guidelines for restoration planning at a watershed
      scale; establishing priorities for improving the delivery of ecosystem services
      at this scale; and prioritizing the sub-watersheds for restoration based on their
      potential for delivering a combination of key ecosystem services for the entire
      basin. 

PMID- 24728488
TI  - Characterization of the zebrafish Ugt repertoire reveals a new class of drug
      metabolizing UDP glucuronosyltransferases.
AB  - The zebrafish genome contains a gene superfamily of 40 Ugt genes that can be
      divided into Ugt1, Ugt2, and Ugt5 families. Because the encoded zebrafish UDP
      glucuronosyltransferase (UGT) proteins do not display orthologous relationships
      to any of the mammalian and avian UGT enzymes based on molecular phylogeny, it is
      difficult to predict their substrate specificity. Here, we mapped their tissue
      specific expression patterns. We showed that the zebrafish UGT enzymes can be
      glycosylated. We determined their substrate specificity and catalytic activity
      toward diverse aglycone substrates. Specifically, we measured mRNA levels of each
      of the 40 zebrafish Ugt genes in 11 adult tissues and found that they are
      expressed in a tissue-specific manner. Moreover, functional analyses with the
      donor of UDP glucuronic acid (UDPGA) for each of the 40 zebrafish UGT proteins
      revealed their substrate specificity toward 10 important aglycones. In
      particular, UGT1A1, UGT1A7, and UGT1B1 displayed good glucuronidation activities
      toward most phenolic aglycones (4-methylumbelliferone, 4-nitrophenol, 1-naphthol,
      bisphenol A, and mycophenolic acid) and the two carboxylic acids (bilirubin and
      diclofenac). Importantly, some members of the UGT5, a novel UGT family identified
      recently, are capable of glucuronidating multiple aglycones with the donor
      cofactor of UDPGA. In particular, UGT5A5, UGT5B2, and UGT5E1 glucuronidate
      phenols and steroids with high specificity toward steroid hormones of estradiol
      and testosterone and estrogenic alkylphenols 4-tert-octylphenol. These results
      shed new insights into the mechanisms by which fish species defend themselves
      against vast numbers of xenobiotics via glucuronidation conjugations and may
      facilitate the establishment of zebrafish as a model vertebrate in toxicological,
      developmental, and pathologic studies. 

PMID- 24728489
TI  - Disturbed circadian rhythm of the intrarenal renin-angiotensin system: relevant
      to nocturnal hypertension and renal damage.
AB  - BACKGROUND: The intrarenal renin-angiotensin system (RAS) plays an important role
      in the development of hypertension and renal damage. Disruption of diurnal blood
      pressure (BP) variation is an additional risk factor for renal damage. However,
      little is known regarding whether intrarenal RAS circadian rhythm exists or if it
      influences the disruption of diurnal BP and renal damage. METHODS: We
      investigated the circadian rhythm of urinary angiotensinogen (U-AGT) that
      reflects intrarenal RAS activity in 14 individuals without chronic kidney disease
      (CKD) and 36 CKD patients classified according to circadian BP rhythms. RESULTS:
      BP values were higher during the daytime than during the nighttime in both
      individuals without CKD and CKD patients. U-AGT levels were not different between
      the daytime and nighttime in individuals without CKD, but were significantly
      higher in the daytime in CKD patients (log U-AGT/creatinine: daytime, 2.39 +/-
      0.99; nighttime, 2.24 +/- 1.06; p = 0.001). Furthermore, in CKD patients showing
      a riser pattern of circadian BP, U-AGT levels did not decrease during the
      nighttime compared with those in the daytime (log U-AGT/creatinine: daytime, 2.51
      +/- 0.65; nighttime, 2.52 +/- 0.71; p = 0.78). Circadian fluctuation of
      albuminuria and proteinuria occurred parallel to that of the U-AGT levels. U-AGT
      levels were significantly and positively correlated with the levels of BP and
      circadian fluctuation of U-AGT was correlated with diurnal BP changes.
      CONCLUSION: These data suggest that the circadian rhythm of intrarenal RAS
      activation may lead to renal damage and hypertension, which are associated with
      diurnal BP variation.

PMID- 24728490
TI  - Extended-spectrum beta-lactamase and carbapenemase-producing Aeromonas species in
      wild animals from Portugal.

PMID- 24728491
TI  - Small ruminant abortions in The Netherlands during lambing season 2012-2013.

PMID- 24728492
TI  - Schedule-dependent synergistic interaction between docetaxel and gefitinib in
      NSCLC cell lines regardless of the mutation status of EGFR and KRAS and its
      molecular mechanisms.
AB  - BACKGROUND: Tyrosine-kinase inhibitors (TKIs) and chemotherapy had different
      pharmacological mechanisms and therefore combined administration of TKIs and
      chemotherapy agents may have synergy. Our research aimed at exploring the
      cytotoxic interactions between gefitinib and docetaxel with different
      concentrations for non-small-cell lung cancer cell lines, and furthermore, the
      mechanisms underlying the cytotoxic synergism. METHODS: NCI-H1650 [epidermal
      growth factor receptor (EGFR) mutation and KRAS wild-type], NCI-H292 (EGFR wild
      type and KRAS wild-type) and A549 (EGFR wild-type and KRAS mutation) cell lines
      were treated with docetaxel and/or gefitinib. Cytotoxic interactions, cell cycle
      distribution and cell signal pathway were analyzed, respectively. RESULTS:
      Cytotoxic interactions between docetaxel and gefitinib were dose-dependent and
      sequence-dependent in all these three cell lines. Docetaxel followed by gefitinib
      treatment was optimum regimen regardless of the mutation status of EGFR and KRAS.
      KRAS mutation and EGFR wild-type predicted insensitive to gefitinib and docetaxel
      combined treatment as well as gefitinib alone. G1 arrest was inconsistently
      associated with combination index (CI). However, apoptosis induction was schedule
      dependent and can explain the synergism completely. Mitogen-activated protein
      kinase (MAPK) phosphorylation ratio was also schedule-dependent and positively
      correlated with CI. CONCLUSION: Cytotoxic interactions between docetaxel and
      gefitinib were sequence-dependent regardless of the mutation status of EGFR and
      KRAS. Cell characteristic, apoptosis induction and MAPK phosphorylation but not
      cell cycle change may explain the molecular mechanisms of synergism.

PMID- 24728494
TI  - New practical approach against sarcoma.

PMID- 24728493
TI  - Overexpression of epithelial cell adhesion molecule protein is associated with
      favorable prognosis in an unselected cohort of ovarian cancer patients.
AB  - PURPOSE: The aim of this study was to evaluate the prognostic influence of
      epithelial cell adhesion molecule (EpCAM) in an unselected cohort of ovarian
      cancer (OC) patients. METHODS: Expression of EpCAM was determined by
      immunohistochemistry in an unselected cohort of 117 patients with OC. Univariable
      and multivariable Cox regression analyses adjusted for age, tumor stage,
      histological grading, histological subtype, postoperative tumor burden and
      completeness of chemotherapy were performed in order to determine the prognostic
      influence of EpCAM. The Kaplan-Meier method is used to estimate survival rates.
      RESULTS: Univariable Cox regression analysis showed that overexpression of EpCAM
      is associated with favorable prognosis in terms of progression-free survival
      (PFS) (p = 0.011) and disease-specific survival (DSS) (p = 0.003). In
      multivariable Cox regression analysis, overexpression of EpCAM retains its
      significance independent of established prognostic factors for longer PFS [hazard
      ratios (HR) 0.408, 95 % confidence interval (CI) 0.197-0.846, p = 0.003] but not
      for PFS (HR 0.666, 95 % CI 0.366-1.212, p = 0.183). Kaplan-Meier plots
      demonstrate an influence on 5-year PFS rates (0 vs. 27.6 %, p = 0.048) and DSS
      rates (11.8 vs. 54.0 %, p = 0.018). CONCLUSIONS: These findings support the
      hypothesis that the expression of EpCAM is associated with favorable prognosis in
      OC.

PMID- 24728495
TI  - Cyclometalated iridium(III)-beta-carboline complexes as potent autophagy-inducing
      agents.
AB  - Two cyclometalated Ir(III)-beta-carboline complexes were identified as potent
      inducers of autophagic cell death. Autophagy induced by these complexes is ROS
      mediated and caspase-independent.

PMID- 24728497
TI  - Crosstalk between fibroblasts and inflammatory cells.
AB  - Fibroblasts, which are traditionally recognized as a quiescent cell responsible
      for extracellular matrix production, are more and more appreciated as an active
      key player of the immune system. This review describes how fibroblasts and immune
      cells reciprocally influence the pathogenesis of fibrosis. An overview is given
      how fibroblasts are triggered by components of the innate and adaptive immunity
      on the one hand and how fibroblasts modulate immune cell behaviour via
      conditioning the cellular and cytokine microenvironment on the other hand.
      Finally, latest insights into the role of cardiac fibroblasts in the
      orchestration of inflammatory cell infiltration in the heart, and their impact on
      heart failure, are outlined. 

PMID- 24728500
TI  - Gene expression signatures for identifying diffuse-type gastric cancer associated
      with epithelial-mesenchymal transition.
AB  - Epithelial-mesenchymal transition (EMT) is associated with tumor malignancy. The
      hedgehog-EMT pathway is preferentially activated in diffuse-type gastric cancer
      (GC) compared with intestinal-type GC; however, histological typing is currently
      the only method for distinguishing these two major types of GC. We compared the
      gene expression profiles of 12 bone marrow-derived mesenchymal stem cell cultures
      and 5 diffuse-type GC tissue samples. Numerous upregulated or downregulated genes
      were identified in diffuse-type GC, including CDH1, CDH2, VIM, WNT4 and WNT5.
      Among these genes, the mRNA ratio of CDH2 to CDH1 could distinguish the 15
      diffuse-type GC samples from the 17 intestinal-type GC samples. Our results
      suggested that the mesenchymal features were more prominent in diffuse-type GC
      than in intestinal-type GC, but were weaker in diffuse-type GC than in
      mesenchymal stem cells. Diffuse-type GC that has undergone extensive EMT, which
      has a poor prognosis, can be identified by quantitative PCR analysis of only two
      genes. 

PMID- 24728499
TI  - Multi-strain infections and 'relapse' of Leucocytozoon sabrazesi gametocytes in
      domestic chickens in southern China.
AB  - Leucocytozoon parasites infect many species of avian hosts, including domestic
      chicken, and can inflict heavy economic loss to the poultry industry. Although
      the prevalence and distribution of two Leucocytozoon species (L. sabrazesi and L.
      caulleryi) have been reported in China previously, there are many questions
      related to the parasite infection that remain unanswered, including population
      diversity and transmission dynamics in domestic chickens. Here we surveyed
      chicken blood samples from seven sites in four provinces of China to identify
      Leucocytozoon infection, characterized parasite diversity within individual
      infected hosts and between sampling sites, and investigated the dynamics of
      gametocytemia in chickens over time. We found high infection rates in three of
      the seven sites. Clustering parasite sequences of the mitochondrial cytochrome
      oxidase III (coxIII) and cytochrome b (cytb) genes showed lack of grouping
      according to geographic origins and individual hosts carrying large numbers of L.
      sabrazesi strains. Monitoring gametocytemia in blood samples from infected
      chickens over time showed 'relapse' or persistence of low-level gametocytemia for
      4-5 months, which could be explored as an in vivo model for testing drugs against
      liver stages of Apicomplexan parasites. This study provides important information
      on population diversity and transmission dynamics of L. sabrazesi and for disease
      control. 

PMID- 24728501
TI  - Localized vibration of a microtubule surrounded by randomly distributed cross
      linkers.
AB  - Based on finite element simulation, the present work studies free vibration of a
      microtubule surrounded by 3D randomly distributed cross linkers in living cells.
      A basic result of the present work is that transverse vibration modes associated
      with the lowest frequencies are highly localized, in sharp contrast to the
      through-length modes predicted by the commonly used classic elastic foundation
      model. Our simulations show that the deflected length of localized modes
      increases with increasing frequency and approaches the entire length of
      microtubule when frequency approaches the minimum classic frequency given by the
      elastic foundation model. In particular, unlike the length-sensitive classic
      frequencies predicted by the elastic foundation model, the lowest frequencies of
      localized modes predicted by the present model are insensitive to the length of
      microtubules and are at least 50% lower than the minimum classic frequency for
      infinitely long microtubules and could be one order of magnitude lower than the
      minimum classic frequency for shorter microtubules (only a few microns in
      length). These results suggest that the existing elastic foundation model may
      have overestimated the lowest frequencies of microtubules in vivo. Finally, based
      on our simulation results, some empirical relations are proposed for the critical
      (lowest) frequency of localized modes and the associated wave length. Compared to
      the classic elastic foundation model, the localized vibration modes and the
      associated wave lengths predicted by the present model are in better agreement
      with some known experimental observations.

PMID- 24728503
TI  - The interaction of carboxylic acids with aluminium oxides: journeying from a
      basic understanding of alumina nanoparticles to water treatment for industrial
      and humanitarian applications.
AB  - Carboxylic acids are found to react with aluminium oxides via a topotactic
      reaction such that the carboxylate acts as a bridging ligand. This reaction
      allows for carboxylate-functionalized alumina nanoparticles to be prepared
      directly from boehmite (AlOOH). Understanding the structural relationship between
      molecular and surface species allows for the rationalization/prediction of
      suitable alternative ligands as well as alternative oxide surfaces. The identity
      of the carboxylate substituent controls the pH stability of a nanoparticle as
      well as the porosity and processability of ceramics prepared by thermolysis.
      Through the choice of functional groups on the carboxylic acid the properties of
      the alumina surface or alumina nanoparticle can be tailored. For example, the
      solubility/miscibility of nanoparticles can be tuned to the solvent/matrix, and
      the wettability to be varied from hydrophobic to super hydrophilic. The choice
      Zwitter ionic substituents on alumina micro-/ultra-filtration membranes are found
      to enhance the flux and limit fouling while allowing for the facile separation of
      organic compounds from water. Examples are presented of purification of frac and
      flow-back water from oil well production as well as providing drinking water from
      contaminated sources in underdeveloped regions. 

PMID- 24728502
TI  - Multiple exposure and effects assessment of heavy metals in the population near
      mining area in South China.
AB  - The objective of this study was to investigate the levels of Cd, Pb, Cu and Zn in
      the environment and several important food sources grown and consumed in the
      vicinity of Dabaoshan mine in Southern China, and evaluate potential health risks
      among local residents. The Cd, Pb, Cu and Zn concentrations of arable soils and
      well water near the mines exceeded the quality standard values. The
      concentrations of Cd and Pb in some food crops (rice grain, vegetable and
      soybean) samples were significantly higher than the maximum permissible level.
      The Cd and Pb concentrations in half of the chicken and fish meat samples were
      higher than the national standard. The residents living near Dabaoshan mine had
      higher Cd and Pb levels in hair than those of a non-exposed population. The
      intake of rice was identified as a major contributor to the estimated daily
      intake of these metals by the residents. The hazard index values for adults and
      children were 10.25 and 11.11, respectively, with most of the estimated risks
      coming from the intake of home-grown rice and vegetables. This study highlights
      the importance of multiple pathways in studying health risk assessment of heavy
      metal exposure in China. 

PMID- 24728504
TI  - Human peripheral neutrophils express functional IL-21 receptors.
AB  - Neutrophils play key roles in the inflammatory response. The IL-21 cytokine and
      receptor system is known to be involved in various inflammatory diseases.
      However, the direct action of IL-21 on neutrophils has not been reported. Here,
      we show that human neutrophils in peripheral blood express functional IL-21
      receptors (IL-21Rs). Expression of the IL-21Ralpha chain (IL-21Ralpha) was
      reduced following various treatments to remove red blood cells, including
      hypotonic shock, ammonium chloride-mediated lysis, and Percoll density
      centrifugation. Thus, we utilized whole blood flow cytometric assays to
      investigate the neutrophil responses to IL-21. IL-21 upregulated the surface
      expression of CD11b and CD16 on neutrophils and augmented the neutrophils'
      phagocytic ability. Our data indicated that IL-21 has the potential to enhance
      the neutrophil functions. 

PMID- 24728505
TI  - Degradation of dibenzothiophene and its metabolite 3-hydroxy-2
      formylbenzothiophene by an environmental isolate.
AB  - Microbial degradation of dibenzothiophene (DBT) beyond 3-hydroxy-2
      formylbenzothiophene (HFBT), a commonly detected metabolite of the Kodama pathway
      for DBT metabolism, and the catabolic intermediates leading to its mineralization
      are not fully understood. The enrichment cultures cultivated from crude oil
      contaminated soil led to isolation of ERI-11; a natural mixed culture, selected
      for its ability to deplete DBT in basal salt medium (BSM). A bacterial strain
      isolated from ERI-11, and tentatively named A11, degraded more than 90 % of the
      initial DBT (270 uM), present as the sole carbon and sulfur source, in 72 h. Gas
      chromatography-mass spectrophotometry (GC-MS) analyses of the DBT degrading A11
      culture medium extracts led to detection of HFBT. The metabolite HFBT, produced
      using A11, was used in degradation assays to evaluate its metabolism by the
      bacteria isolated in this study. Ultra violet-visible spectrophotometry and high
      performance liquid chromatography analyses established the ability of the strain
      A11 to deplete HFBT, present as the sole sulfur and carbon source in BSM. GC-MS
      analyses showed the presence of 2-mercaptobenzoic acid in the HFBT degrading A11
      culture extracts. The findings in this study establish that the environmental
      isolate A11 possesses the metabolic capacity to degrade DBT beyond the metabolite
      HFBT. The compound 2-mercaptobenzoic acid is an intermediate formed on HFBT
      degradation by A11.

PMID- 24728506
TI  - Phanerochaete chrysosporium inoculation shapes the indigenous fungal communities
      during agricultural waste composting.
AB  - Inoculation with exogenous white-rot fungi has been proven to be an efficient
      method to promote lignocellulose biodegradation during agricultural waste
      composting. Indigenous fungal communities, the most important organisms
      responsible for mineralization and decomposition of lignocellulosic materials in
      composts, can be affected by sample properties and other biotic factors. This
      research was conducted to determine the effects of the Phanerochaete
      chrysosporium inoculation on the indigenous fungal communities during
      agricultural waste composting. Fungal communities in samples with different
      inoculation regimes were investigated by sequencing and quantitative PCR. Results
      showed that P. chrysosporium inoculants produced significant negative effects on
      the indigenous fungal community abundance during the thermophilic stage. Samples
      inoculated during Phase II contained higher proportion of Acremonium chrysogenum
      and Galactomyces geotrichum, while those non-inoculated samples were dominated by
      Coprinopsis cinerea and Scytalidium thermophilum. Moreover, the indigenous fungal
      community abundance was significantly correlated with the C/N ratio, water
      soluble carbon and moisture content (P < 0.05). Redundancy analysis indicated
      that the most variation in distribution of indigenous fungal community structure
      was statistically explained by nitrate, C/N ratio, and moisture content, factors
      which solely explained 29.6 % (F = 30.316, P = 0.002), 25.6 % (F = 26.191, P =
      0.002) and 10.0 % (F = 10.249, P = 0.002) of the variation in the indigenous
      fungal community structure, respectively.

PMID- 24728507
TI  - Structures of ionic liquid-water mixtures investigated by IR and NMR
      spectroscopy.
AB  - Imidazolium-based ionic liquids having different anions 1-butyl-3
      methylimidazolium ([BMIM]X: X = Cl(-), Br(-), I(-), and BF4(-)) and their aqueous
      mixtures were investigated by IR absorption and proton NMR spectroscopy. The IR
      spectra of these ionic liquids in the CHx stretching region differed
      substantially, especially for C-H bonds in the imidazolium ring, and the NMR
      chemical shifts of protons in the imidazolium ring also varied markedly for ILs
      having different anions. Upon the introduction of water to screen the
      electrostatic forces and separate the ions, both IR and NMR spectra of [BMIM]X (X
      = Cl(-), Br(-), I(-)) showed significant changes, while those of [BMIM]BF4 did
      not change appreciably. H-D isotopic exchange rates of C(2)-H in [BMIM]X-D2O
      mixtures exhibited an order: C(2)-HCl > C(2)-HBr > C(2)-HI, while the C(2)-H of
      [BMIM]BF4 was not deuterated at all. These experimental findings, supported by
      DFT calculations, lead to the microscopic bulk configurations in which the anions
      and the protons of the cations in the halide ionic liquids have specific,
      hydrogen-bond type of interaction, while the BF4(-) anion does not participate in
      the specific interaction, but interacts less specifically by positioning itself
      more above the ring plane of the imidazolium cation. This structural change
      dictated by the anion type will work as a key element to build the structure
      property relationship of ionic liquids. 

PMID- 24728509
TI  - Differentiation of human pluripotent stem cells into nephron progenitor cells in
      a serum and feeder free system.
AB  - OBJECTIVES: Kidney disease is emerging as a critical medical problem worldwide.
      Because of limited treatment options for the damaged kidney, stem cell treatment
      is becoming an alternative therapeutic approach. Of many possible human stem cell
      sources, pluripotent stem cells are most attractive due to their self-renewal and
      pluripotent capacity. However, little is known about the derivation of renal
      lineage cells from human pluripotent stem cells (hPSCs). In this study, we
      developed a novel protocol for differentiation of nephron progenitor cells (NPCs)
      from hPSCs in a serum- and feeder-free system. MATERIALS AND METHODS: We designed
      step-wise protocols for differentiation of human pluripotent stem cells toward
      primitive streak, intermediate mesoderm and NPCs by recapitulating normal
      nephrogenesis. Expression of key marker genes was examined by RT-PCR, real time
      RT-PCR and immunocytochemistry. Each experiment was independently performed three
      times to confirm its reproducibility. RESULTS: After modification of culture
      period and concentration of exogenous factors, hPSCs can differentiate into NPCs
      that markedly express specific marker genes such as SIX2, GDNF, HOXD11, WT1 and
      CITED1 in addition to OSR1, PAX2, SALL1 and EYA1. Moreover, NPCs possess the
      potential of bidirectional differentiation into both renal tubular epithelial
      cells and glomerular podocytes in defined culture conditions. In particular,
      approximately 70% of SYN-positive cells were obtained from hPSC-derived NPCs
      after podocytes induction. NPCs can also form in vitro tubule-like structures in
      three dimensional culture systems. CONCLUSIONS: Our novel protocol for hPSCs
      differentiation into NPCs can be useful for producing alternative sources of cell
      replacement therapy and disease modeling for human kidney diseases.

PMID- 24728510
TI  - Stimuli-responsive one-dimensional copolymer nanostructures fabricated by
      metallogel template polymerization and their adsorption of aspirin.
AB  - pH responsive poly(N,N'-methylenebisacrylamide-co-4-vinylpyridine) (P(MBA-4VP))
      one dimensional (1D) nanostructures have been prepared by metallogel template
      copolymerization, which was carried out in an Ag(i)-coordinated organogel with
      benzoyl peroxide (BPO) as the initiator. The product has been characterized using
      infrared spectroscopy, scanning electron microscopy and transmission electron
      microscopy. The experimental results reveal that the gel fiber is a crucial
      template for polymerization. Due to the degradation of the template in
      copolymerization, nanofibers of metallogel were transcribed to copolymer
      nanowires. The introduction of co-monomer 4-vinylpyridine (4VP) imparts to the 1D
      copolymer nanostructures pH sensitivity and the possible use as an adsorption
      material of aspirin. Adsorbed 1D copolymer nanostructures could be regenerated
      using proton solvent, acid medium and salt solution. In addition, silver
      nanoparticle loaded copolymer nanowires have been produced from the reduction of
      silver ions instead of template removal, where silver ions act both as the
      template and as the nanoparticle growth substrate. 

PMID- 24728511
TI  - Influenza vaccination by pharmacists in a health sciences center: A 3-year
      experience.
AB  - OBJECTIVE: To assess the design and implementation of influenza vaccination
      clinics across campus, assess participant satisfaction with the pharmacist-led
      clinics, and educate and increase visibility of the role of pharmacists as
      vaccinators. SETTING: University of Oklahoma Health Sciences Center (OUHSC), a
      comprehensive health sciences center. PRACTICE INNOVATION: The College of
      Pharmacy on the OUHSC campus developed and implemented a vaccination program to
      increase influenza vaccination of OUHSC employees. MAIN OUTCOME MEASURES: Number
      of employees receiving influenza vaccination, employee satisfaction with the
      pharmacist-led clinics, and employee awareness of the pharmacist's role in
      vaccination. RESULTS: Reported OUHSC employee influenza vaccination rates
      increased from approximately 35% before implementation of the pharmacy-based
      program to 54% in 2012 after implementation. The increase was attributed to
      maintaining no out-of-pocket costs for employees, offering various clinic
      locations, and using media resources to educate employees about influenza
      infection and vaccination. Employees reported high satisfaction with the
      influenza vaccination clinics and with receiving vaccinations from pharmacists
      and student pharmacists. In the first 2 years of the program, the percentage of
      surveyed employees "very familiar" with the pharmacist's role in vaccinations
      increased from 23% to 66%. CONCLUSION: A college of pharmacy on a large health
      sciences center developed and successfully implemented an influenza vaccination
      program, providing an accessible and convenient route for influenza prevention to
      employees, as well as enhanced the visibility of pharmacists as vaccination
      providers.

PMID- 24728512
TI  - Afatinib, a lung cancer inhibitor of ErbB family.

PMID- 24728513
TI  - Italian risk-sharing agreements on drugs: are they worthwhile?

PMID- 24728516
TI  - Rare cutaneous manifestations associated with Crohn's disease.

PMID- 24728515
TI  - Influence of CD68+ macrophages and neutrophils on anastomotic healing following
      laparoscopic sigmoid resection due to diverticulitis.
AB  - BACKGROUND: The aim of this prospective study was to evaluate the predictive
      value of a potential preexisting low-grade inflammation regarding the incidence
      of anastomotic leakage in elective laparoscopic sigmoid resection due to
      diverticulitis. METHODS: Patients with either chronically recurrent
      diverticulitis or sigmoid stenosis caused by chronic diverticulitis were included
      in this study. All patients with acute local or systemic inflammation were
      excluded. Detailed patient information (e.g. American Society of
      Anesthesiologists (ASA) grade, comorbidities, duration of hospital stay, and
      anastomotic leakage) was prospectively recorded. CD68(+) macrophages,
      neutrophils, CD3(+) T-lymphocytes, CD11c(+) dendritic cells, MHCII, TNFR1, and NF
      kappaB were evaluated by immunohistochemistry within the acquired sample of
      colonic bowel wall tissue. Clinical and immunohistochemical data was compared
      between groups (leakage vs. no leakage). Additionally, a matched-pair analysis
      was performed due to the widely heterogeneous groups concerning the number of
      patients and to minimize the effect of extraneous variables. RESULTS: A total of
      83 patients were included in the study, of which 7 patients suffered an
      anastomotic leakage. Neither the clinical nor the immunohistochemical parameters
      were significantly different between the groups. The matched-pair analysis
      revealed a nonsignificant increase in mean duration of hospital stay for the
      group with anastomotic leakage and a significantly higher percentage of CD68(+)
      macrophages and neutrophils in the colonic wall obtained at the index operation
      in both the mucosal and submucosal layers for the leakage group. CONCLUSIONS: A
      preexisting low-grade inflammation represented by infiltrates of macrophages and
      neutrophils is a predictor for increased risk of developing colon anastomotic
      leakage.

PMID- 24728517
TI  - Can hyperthermic intraperitoneal chemotherapy efficiency be improved by blocking
      the DNA repair factor COP9 signalosome?
AB  - PURPOSE: A frequently used chemotherapeutic agent in hyperthermic intraperitoneal
      chemotherapy (HIPEC) is mitomycin C (MMC) which induces DNA damage and apoptosis
      in tumor cells. In addition, MMC activates DNA damage response (DDR) leading to
      repair mechanisms counteracting the effect of chemotherapy. COP9 signalosome
      (CSN) positively influences the DDR pathway by its intrinsic deneddylating and
      associated kinase activities. In an in vitro HIPEC model, we studied the impact
      of curcumin, an inhibitor of CSN-associated kinases, and of the microRNA (miRNA)
      let-7a-1, an inhibitor of CSN subunit expression, on the MMC-induced apoptosis in
      human HT29 colon cancer cells. METHODS: Cells were incubated at 37  degrees C and
      indicated concentrations of MMC in a medium preheated to 42  degrees C as under
      HIPEC conditions for 1 or 4 h. HT29 cells were cotreated with 50 MUM curcumin or
      transfected with let-7a-1 miRNA mimic. After incubation, cells were analyzed by
      Western blotting, densitometry, and caspase-3 ELISA. RESULTS: An increase of CSN
      subunits in response to MMC treatment was detected. Apoptosis was only measured
      after 4 h with 50 MUM MMC. MMC-induced apoptosis was elevated by cotreatment with
      curcumin. Transfection of HT29 cells with let-7a-1 reduced the expression of
      tested CSN subunits associated with the accumulation of the pro-apoptotic factors
      p27 and p53. CONCLUSIONS: In response to MMC treatment, the CSN is elevated as a
      regulator of DDR retarding apoptosis in tumor cells. The therapeutic effect of
      HIPEC can be increased by inhibiting CSN-associated kinases via curcumin or by
      blocking CSN expression with let-7a-1 miRNA.

PMID- 24728518
TI  - Sarcocystis schneideri n. sp. (Sarcocystidae) infecting the barber skink Eumeces
      schneideri schneideri (Scincidae) Daudin, 1802. A light and ultrastructural
      study.
AB  - The current study provides the first record of infection with Sarcocystis species
      in the barber skink Eumeces schneideri schneideri (Scincidae) captured from the
      north region of Egypt around the cities of El-Hamam and Al-Dabaa, Mersa Matruh
      Governorate, Egypt. Morphology of the parasite cysts was described using light
      and transmission electron microscopy. Five out of 80 (6.25%) of the examined
      skinks were found to be infected. The infection was recorded firstly by light
      microscopy as spindle-shaped cysts embedded in the muscle tissue. The cysts were
      microscopic and measured 250-900 MUm in length * 50-100 MUm in width (mean, 575 *
      75 MUm). The validity of this species was confirmed by means of ultrastructural
      characteristics of the primary cyst wall (0.28 MUm thick) which revealed the
      presence of irregularly shaped crowded and osmiophilic knob-like projections
      underlined by a thin layer of ground substance measuring 0.15-0.17 MUm (mean,
      0.16 MUm). This layer consisted mainly of fine, dense homogenous granules
      enclosing the developing metrocytes and merozoites that usually contain nearly
      all the structures of the apical complex and fill the interior cavity of the
      cyst. Several septa derived from the ground substance divided the cyst into
      compartments. The merozoites were banana-shaped and measured 3-5 MUm in length
      and 1.5-2.5 in width with centrally or posteriorly located nuclei. The
      morphological and morphometric data obtained during study were compared with
      those recorded previously from organisms within the Scincidae family. It was
      observed that this parasite possessed some distinguishing characteristics from
      the comparable species, which should be considered as a new species of the
      Sarcocystis genus, and the proposed name was Sarcocystis schneideri n. sp. with
      new host and locality records in Egypt.

PMID- 24728519
TI  - Ketanserin, an antidepressant, exerts its antileishmanial action via inhibition
      of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR) enzyme of Leishmania
      donovani.
AB  - Leishmaniasis is one of the major health problems existing globally. The current
      chemotherapy for leishmaniasis presents several drawbacks like toxicity and
      increased resistance to existing drugs, and hence, there is a necessity to look
      out for the novel drug targets and new chemical entities. Current trend in drug
      discovery arena is the "repurposing" of old drugs for the treatment of diseases.
      In the present study, an antidepressant, ketanserin, was found lethal to both
      Leishmania donovani promastigotes and intracellular amastigotes with no apparent
      toxicity to the cells. Ketanserin killed promastigotes and amastigotes with an
      IC50 value of 37 MUM and 28 MUM respectively, in a dose-dependent manner.
      Ketanserin was found to inhibit L. donovani recombinant 3-hydroxy-3
      methylglutaryl coenzyme A reductase (HMGR) enzyme with an IC50 value of 43 MUM.
      Ketanserin treated promastigotes were exogenously supplemented with sterols like
      ergosterol and cholesterol to rescue cell death. Ergosterol could recover the
      inhibition partially, whereas cholesterol supplementation completely failed to
      rescue the inhibited parasites. Further, HMGR-overexpressing parasites were
      generated by transfecting Leishmania promastigotes with an episomal pspalpha
      hygroalpha-HMGR construct. Wild-type and HMGR overexpressors of L. donovani were
      used to study the effect and mode of action of this inhibitor. The HMGR
      overexpressors showed twofold resistance to ketanserin. These observations
      suggest that the lethal effect of ketanserin is due to inhibition of HMGR, the
      rate-limiting enzyme of the ergosterol biosynthetic pathway. Since targeting of
      the sterol biosynthetic pathway enzymes may be useful therapeutically, the
      present study may have implications in treatment of leishmaniasis. 

PMID- 24728520
TI  - Species-specific markers for the differential diagnosis of Trypanosoma cruzi and
      Trypanosoma rangeli and polymorphisms detection in Trypanosoma rangeli.
AB  - Trypanosoma cruzi and Trypanosoma rangeli are kinetoplastid parasites which are
      able to infect humans in Central and South America. Misdiagnosis between these
      trypanosomes can be avoided by targeting barcoding sequences or genes of each
      organism. This work aims to analyze the feasibility of using species-specific
      markers for identification of intraspecific polymorphisms and as target for
      diagnostic methods by PCR. Accordingly, primers which are able to specifically
      detect T. cruzi or T. rangeli genomic DNA were characterized. The use of
      intergenic regions, generally divergent in the trypanosomatids, and the serine
      carboxypeptidase gene were successful. Using T. rangeli genomic sequences for the
      identification of group-specific polymorphisms and a polymorphic AT(n)
      dinucleotide repeat permitted the classification of the strains into two groups,
      which are entirely coincident with T. rangeli main lineages, KP1 (+) and KP1 (-),
      previously determined by kinetoplast DNA (kDNA) characterization. The sequences
      analyzed totalize 622 bp (382 bp represent a hypothetical protein sequence, and
      240 bp represent an anonymous sequence), and of these, 581 (93.3%) are conserved
      sites and 41 bp (6.7%) are polymorphic, with 9 transitions (21.9%), 2
      transversions (4.9%), and 30 (73.2%) insertion/deletion events. Taken together,
      the species-specific markers analyzed may be useful for the development of new
      strategies for the accurate diagnosis of infections. Furthermore, the
      identification of T. rangeli polymorphisms has a direct impact in the
      understanding of the population structure of this parasite.

PMID- 24728521
TI  - Longevity of Sm-p80-specific antibody responses following vaccination with Sm-p80
      vaccine in mice and baboons and transplacental transfer of Sm-p80-specific
      antibodies in a baboon.
AB  - Based on data obtained using vaccine efficacy studies in mice, hamsters, and
      baboons, the credentials of Sm-p80 as a first tier vaccine candidate for
      schistosomiasis have been well established. Sm-p80-based vaccine formulation(s)
      have consistently exhibited potent prophylactic efficacy in reducing adult worm
      burden following cercarial challenge and induce killing of established adult
      worms in chronic infection. This vaccine is protective against both intestinal
      and urinary schistosomiasis. In this study, the longevity of Sm-p80-specific
      antibody responses was studied in mice and in baboons. Robust antibody titers
      were detected in mice for up to 60 weeks following vaccination with Sm-p80
      recombinant vaccine (Sm-p80 + GLA-SE). In the follow-up experiments to our
      published studies, Sm-p80-specific IgG was also detected in baboons 5-8 years
      following the initial vaccination with an Sm-p80 DNA vaccine. In one baboon,
      transfer of Sm-p80-specific antibody was detected in umbilical cord blood and in
      the baby. These long-lasting humoral immune response data coupled with the
      vaccine efficacy data in rodents and nonhuman primates further strengthens the
      case for Sm-p80 to be moved forward through development leading to human clinical
      trials. 

PMID- 24728522
TI  - A scanning electron microscopy study of Argulus vittatus (Rafinesque-Schmaltz,
      1814) (Crustacea: Branchiura) from Algerian coast.
AB  - A study of the Algerian Branchiura, Argulus vittatus (Rafinesque-Schmaltz, 1814)
      was conducted using the scanning electron microscopy (SEM). New morphological
      features are reported for the first time (mouth con, first maxilla, second
      maxilla, structures and ornamentation of thoracic segments, structure of semen
      papillae, etc.). The morphology of small and large female specimens was compared.
      Two new hosts, Pagellus erythrinus L. and Sparus aurata L., are reported for this
      species. Until now, six host species were reported for A. vittatus, and
      stenoxenic specificity for Sparid fishes was observed for Algerian specimens. The
      biogeographical distribution of this species seems to be restricted to the
      eastern coast of Algeria. Additional information about the host specificity,
      ecology, and life cycle of this parasitic species were given. 

PMID- 24728523
TI  - Developmental rate, size, and sexual dimorphism of Megaselia scalaris (Loew)
      (Diptera: Phoridae): its possible implications in forensic entomology.
AB  - Cosmopolitan scuttle fly, Megaselia scalaris (Loew) (Diptera: Phoridae) is one of
      the commonest forensic species recorded colonizing human corpse indoors and in
      concealed environment. The occurrence of this species in such environments
      provides a higher evidential value to assist estimation of postmortem interval
      (PMI) compared to other forensically important dipterans. However, developmental
      and size data of M. scalaris are still lacking and they are derived from a
      limited range of thermal values. The objective of this study is to develop the
      growth model of M. scalaris by emphasizing the size range of larvae and puparia
      at different constant temperatures. This species was reared in six replicates at
      eight varying constant temperatures ranging from 23 to 36  degrees C and cow's
      liver was provided as food source. Larvae and puparia were sampled at set time
      intervals and measured by their length and weight. Because interpretation of
      forensic entomological evidence is subject to application of different
      techniques, development of M. scalaris is expressed herein by using developmental
      table, length/morphological stage diagrams and linear/nonlinear estimation
      methods. From the findings, it is very important to highlight that sexual
      dimorphism of M. scalaris during post feeding larva and pupa stage could be
      observed based on size and developmental periods. Mean length and weight ratios
      of male to female puparia are approximately 0.8 and 0.3-0.5, respectively,
      indicating sexual dimorphism of this species. Developmental period in female are
      4.0-11.4 h (post feeding larval stage), 3.7-24.0 h (pupal stage), and 3.0-20.1 h
      (total developmental period) longer in male. Due to this dimorphism, PMI
      estimation using M. scalaris post feeding larva or puparium specimens must be
      carried out carefully by to avoid inaccuracy and misinterpretation. 

PMID- 24728525
TI  - Lanthanide anilido complexes: synthesis, characterization, and use as highly
      efficient catalysts for hydrophosphonylation of aldehydes and unactivated
      ketones.
AB  - Lanthanide anilido complexes stabilized by the 2,6-diisopropylanilido ligand have
      been synthesized and characterized, and their catalytic activity for
      hydrophosphonylation reaction was explored. A reaction of anhydrous LnCl3 with 5
      equivalents of LiNHPh-(I)Pr2-2,6 in THF generated the heterobimetallic lanthanide
      lithium anilido complexes (2,6-(I)Pr2PhNH)5LnLi2(THF)2 [Ln = Sm(1), Nd(2), Y(3)]
      in good isolated yields. These complexes are well characterized by elemental
      analysis, IR, NMR (for complex ) and single-crystal structure determination.
      Complexes 1 - 3 are isostructural. In these complexes, the lanthanide metal ion
      is five-coordinated by five nitrogen atoms from five 2,6-diisopropylanilido
      ligands to form a distorted trigonal bipyramidal geometry. The lithium ion is
      coordinated by two nitrogen atoms from two 2,6-diisopropylanilido ligands, and
      one oxygen atom from a THF molecule. It was found that these simple lanthanide
      anilido complexes are highly efficient for catalyzing hydrophosphonylation
      reactions of various aldehydes and unactivated ketones to generate alpha
      hydroxyphosphonates in good to excellent yields (up to 99%) within a short time
      (5 min for aldehydes, 20 min for ketones). Furthermore, the mechanism of
      hydrophosphonylation reactions has also been elucidated via(1)H NMR monitoring of
      reaction.

PMID- 24728526
TI  - Arcellacea (testate amoebae) as bio-indicators of road salt contamination in
      lakes.
AB  - Winter deicing operations occur extensively in mid- to high-latitude metropolitan
      regions around the world and result in a significant reduction in road accidents.
      Deicing salts can, however, pose a major threat to water quality and aquatic
      organisms. In this paper, we examine the utility of Arcellacea (testate amoebae)
      for monitoring lakes that have become contaminated by winter deicing salts,
      particularly sodium chloride. We analysed 50 sediment samples and salt-related
      water property variables (chloride concentrations; conductivity) from 15 lakes in
      the Greater Toronto Area and adjacent areas of southern Ontario, Canada. The
      sampled lakes included lakes in proximity to major highways and suburban roads
      and control lakes in forested settings away from road influences. Samples from
      the most contaminated lakes, with chloride concentrations in excess of 400 mg/l
      and conductivities of >800 MUS/cm, were dominated by species typically found in
      brackish and/or inhospitable lake environments and by lower faunal diversities
      (lowest Shannon diversity index values) than samples with lower readings. Q-R
      mode cluster analysis and detrended correspondence analysis (DCA) resulted in the
      recognition of four assemblage groupings. These reflect varying levels of salt
      contamination in the study lakes, along with other local influences, including
      nutrient loading. The response to nutrients can, however, be isolated if the
      planktic eutrophic indicator species Cucurbitella tricuspis is removed from the
      counts. The findings show that the group has considerable potential for
      biomonitoring in salt-contaminated lakes, and their presence in lake sediment
      cores may provide significant insights into long-term benthic community health,
      which is integral for remedial efforts.

PMID- 24728527
TI  - Metabolomic analysis of cooperative adaptation between co-cultured Bacillus
      cereus and Ketogulonicigenium vulgare.
AB  - The cooperative adaptation of subcultivated Bacillus cereus and
      Ketogulonicigenium vulgare significantly increased the productivity of 2-keto-L
      gulonic acid, the precursor of vitamin C. The mechanism of cooperative adaptation
      of the serial subcultivated B. cereus and K. vulgare was investigated in this
      study by culturing the two strains orthogonally on agar plates. It was found that
      the swarming distance of B. cereus along the trace of K. vulgare on the plate
      decreased after 150 days' subcultivation. Metabolomic analysis on these co
      cultured B. cereus and K. vulgare strains showed that their cooperative
      adaptation was accomplished by three key events: (i) the ability of nutrients
      (e.g., amino acids and purines) searching and intaking, and proteins biosynthesis
      is increased in the evolved B. cereus; (ii) the capability of protein degradation
      and amino acids transportation is enhanced in evolved K. vulgare; (iii) the
      evolved B. cereus was found to provide more nutrients (mostly amino acids and
      purines) to K. vulgare, thus strengthening the oxidation and energy generation of
      K. vulgare. Our results provided novel insights into the systems-level
      understanding of the cooperative adaptation between strains in synergistic
      consortium. 

PMID- 24728528
TI  - Anthropological engagements with modern psychotropy.

PMID- 24728529
TI  - Orthodontic treatment with fixed appliances and biofilm formation--a potential
      public health threat?
AB  - OBJECTIVES: Orthodontic treatment is highly popular for restoring functional and
      facial esthetics in juveniles and adults. As a downside, prevalence of biofilm
      related complications is high. Objectives of this review are to (1) identify
      special features of biofilm formation in orthodontic patients and (2) emphasize
      the need for strong concerted action to prevent biofilm-related complications
      during orthodontic treatment. MATERIALS AND METHODS: Literature on biofilm
      formation in the oral cavity is reviewed to identify special features of biofilm
      formation in orthodontic patients. Estimates are made of juvenile and adult
      orthodontic patient population sizes, and biofilm-related complication rates are
      used to indicate the costs and clinical workload resulting from biofilm-related
      complications. RESULTS: Biofilm formation in orthodontic patients is governed by
      similar mechanisms as common in the oral cavity. However, orthodontic appliances
      hamper the maintenance of oral hygiene and provide numerous additional surfaces,
      with properties alien to the oral cavity, to which bacteria can adhere and form a
      biofilm. Biofilm formation may lead to gingivitis and white spot lesions,
      compromising facial esthetics. Whereas gingivitis after orthodontic treatment is
      often transient, white spot lesions may turn into cavities requiring professional
      restoration. Complications requiring professional care develop in 15 % of all
      orthodontic patients, implying an annual cost of over US$500,000,000 and a
      workload of 1,000 full-time dentists in the USA alone. CONCLUSIONS: Improved
      preventive measures and antimicrobial materials are urgently required to prevent
      biofilm-related complications of orthodontic treatment from overshadowing its
      functional and esthetic advantages. CLINICAL RELEVANCE: High treatment demand and
      occurrence of biofilm-related complications requiring professional care make
      orthodontic treatment a potential public health threat.

PMID- 24728531
TI  - Ghrelin gene products in acute and chronic inflammation.
AB  - Ghrelin gene products--the peptides ghrelin, unacylated ghrelin, and obestatin-
      have several actions on the immune system, opening new perspectives within
      neuroendocrinology, metabolism and inflammation. The aim of this review is to
      summarize the available evidence regarding the less known role of these peptides
      in the machinery of inflammation and autoimmunity, outlining some of their most
      promising therapeutic applications.

PMID- 24728530
TI  - [Psychosomatic aspects of chronic pelvic pain syndrome. Psychometric results from
      the pilot phase of an interdisciplinary outpatient clinic].
AB  - BACKGROUND: Chronic pelvic pain syndrome (CPPS) presents as a multicausal
      disorder. Complex interactions of psychological factors with somatic dysfunctions
      are crucial to the development and maintenance of CPPS. AIM: This study
      characterized the patient cohort from a psychosomatic perspective. MATERIAL AND
      METHODS: Subjects with CPPS were recruited from an interdisciplinary CPP
      outpatient clinic. Sociodemographic data, symptoms (National Institutes of Health
      Chronic Prostatitis Symptom Index, NIH-CPSI) and pain-related factors (Short Form
      of the McGill Pain Questionnaire, SF-MPQ) as well as depressive symptoms (Patient
      Health Questionnaire 9, PHQ-9), anxiety [Generalized Anxiety Disorder 7-item (GAD
      7) Scale], the severity of somatic symptoms (PHQ-15) and quality of life (Short
      Form-12, SF-12) were measured. Additional socioeconomic data were obtained.
      RESULTS: A total of 50 men and women with a mean disease duration of 5.8 years
      were included in the study. The disease-related symptom severity and healthcare
      utilization were high. All psychometric scales showed significantly lower values
      compared with the general population. A high symptom burden was associated with
      high psychopathological findings and reduced quality of life. CONCLUSION: The
      psychopathological comorbidities in subjects with CPPS require specific evidence
      based diagnostic and treatment methods to reduce psychopathology and improve
      quality of life.

PMID- 24728532
TI  - Isomer-selective infrared spectroscopy of the cationic trimethylamine dimer to
      reveal its charge sharing and enhanced acidity of the methyl groups.
AB  - Infrared predissociation spectroscopy of the trimethylamine dimer cation
      generated by the vacuum-ultraviolet photoionization is isomer-selectively carried
      out by monitoring two main fragment channels, protonated trimethylamine and the
      trimethylamine monomer cation. The spectral carriers monitored by these two
      channels are assigned to different isomers of the trimethylamine dimer cation.
      One is the charge-shared (hemibond) structure, in which the positive charge is
      intermolecularly delocalized over the dimer through the interaction between the
      nonbonding orbitals of the nitrogen atoms. In the other isomer, a proton of a
      methyl group in the ionized moiety is intermolecularly transferred to the
      nitrogen atom of the neutral moiety and is shared between the carbon and nitrogen
      atoms. The latter isomer shows that the methyl groups of cationic trimethylamine
      are highly acidic. This example demonstrates characteristic properties of radical
      cations with alkyl groups. 

PMID- 24728533
TI  - Phacoemulsification versus peripheral iridotomy in the management of chronic
      primary angle closure: long-term follow-up.
AB  - Primary angle closure occurs as a result of crowded anterior segment anatomy,
      causing appositional contact between the peripheral iris and trabecular meshwork,
      thereby obstructing aqueous outflow. Several studies highlight the role of the
      crystalline lens in its pathogenesis. The objective of this work is to compare
      the long-term efficacy of phacoemulsification versus laser peripheral iridotomy
      (LPI) in the management of chronic primary angle closure (CPAC). Prospective case
      control study with 30 eyes of 30 patients randomly divided in two groups: 15 eyes
      in the LPI group and 15 eyes in the IOL group. Patients in the LPI group
      underwent LPI using argon and Nd:YAG laser. Patients in the IOL group underwent
      phacoemulsification with posterior chamber intraocular lens (IOL) implantation.
      Examinations before and after the procedure included gonioscopy, Goldmann
      applanation tonometry, and anterior chamber evaluation using the Pentacam
      rotating Scheimpflug camera. The mean follow-up time was 31.13 +/- 4.97 months.
      There was a statistically significant reduction in the intraocular pressure (IOP)
      and number of anti-glaucoma medications (p < 0.01) only in the IOL group.
      Anterior chamber depth, angle, and volume were all higher in the IOL group (p <
      0.01) at the end of the follow-up period. Phacoemulsification with posterior
      chamber IOL implantation results in a higher anterior chamber depth, angle, and
      volume, when compared to LPI. Consequently, phacoemulsification has greater
      efficacy in lowering IOP and preventing its long-term increase in patients with
      CPAC and cataract. 

PMID- 24728534
TI  - Sutureless clear corneal DSAEK with a modified approach for preventing pupillary
      block and graft dislocation: case series with retrospective comparative analysis.
AB  - The purpose of this study was to describe a modified technique of sutureless
      DSAEK with continuous pressurized internal air tamponade. This was a prospective
      interventional case series, single-center, institutional study. Twenty-seven
      patients with corneal decompensation without scarring were included. Aphakic
      patients and patients with cataractous lens requiring IOL implantation surgery
      were excluded. Following preparation of the donor tissue, a corneal tunnel was
      made nasally with two side ports. All incisions were kept long enough to be
      overlapped by the peripheral part of the donor tissue. Descemet membrane scoring
      was done using a reverse Sinskey hook, following which it was removed with the
      same instrument or by forceps. The donor lenticule was then inserted using
      Busin's glide. Continuous pressurized internal air tamponade was achieved by
      means of a 30-gauge needle, inserted through the posterior limbus, for 12-14 min.
      At the end of the surgery, air was partially replaced with BSS, leaving a
      moderate-sized mobile air bubble in the anterior chamber. At the 6 month's follow
      up, CDVA improved from counting fingers at half meter-6/24 preoperatively to 6/9
      6/18 postoperatively, and the mean endothelial cell count decreased: to 1,800
      from 2,200 cell/mm(2) preoperatively (18.19 % endothelial cell loss). Donor
      lenticule thickness as documented on AS-OCT was 70-110 u on Day 1 and 50-80 u at
      6 months postoperative. None of the cases had flat AC or peripheral anterior
      synechiae formation. None of the patients required a second intervention. There
      were no cases of primary graft failure, pupillary block glaucomax or donor
      lenticule dislocation postoperatively. Our modified technique is simple and
      effective with reduction in postoperative complications associated with DSAEK,
      thereby maximizing anatomic and functional outcomes associated. 

PMID- 24728535
TI  - Optic neuritis in Hong Kong: a 1-year follow-up study.
AB  - To investigate the etiology and prevalence of optic neuritis in a Chinese
      population. This was a single centre prospective cohort study. Consecutive
      patients with either a first or recurrent attack of optic neuritis from November
      2010 to December 2011 were recruited from a district hospital in Hong Kong
      Special Administrative Region, China. All patients underwent serology testing for
      NMO (neuromyelitis optica) IgG; oligoclonal bands from lumbar puncture; computer
      tomography and contrast magnetic resonance imaging (MRI) of the brain and orbit
      as well as visual field; and optical coherence tomography testing. Patients were
      followed up for 1 year after the initial attack. 30 optic neuritis subjects were
      recruited. 73.3 % (22/30) remain as clinical isolated syndrome (CIS) after 1-year
      follow-up. 10 % (3/30) patients developed multiple sclerosis. 10 % (3/30) were
      diagnosed with NMO and 6.7 % (2/30) with NMO-spectrum disorder. The majority of
      acute unilateral optic neuritis in Chinese was CIS in origin although a fraction
      does progress to develop MS or NMO-related disorders. Clinicians should be aware
      of the associations and offer appropriate systemic workups.

PMID- 24728536
TI  - Surgical treatment of endemic goiter in a nonhospital setting without general
      anesthesia in Africa.
AB  - BACKGROUND: Endemic goiter remains a serious public health problem and 75 % of
      people affected live in underdeveloped countries where treatment is difficult for
      various reasons. The aim of this article is to report our experience in African
      countries with the management and surgical treatment of endemic goiter, performed
      in a nonhospital setting and without general anesthesia in the context of a
      collaborative development project by experienced endocrine surgeons. METHODS:
      Fifty-six black African patients with a goiter were studied. Those in poor
      general health, the elderly, patients with either small goiters or clinical
      hyperthyroidism, and those presenting with an acute episode of malaria were
      excluded from the study. Cervical epidural anesthesia with spontaneous
      ventilation was used and a partial thyroidectomy was performed. The technique
      used, its immediate complications, and early and late follow-up were analyzed.
      RESULTS: Surgery was performed on 31 patients with grades 3 and 4 goiter without
      mortality and a morbidity rate of 11.9 %, with 97 % of all complications being
      minor. There were no instances of dysphonia or symptomatic hypocalcemia and the
      mean stay was 1.57 days (range 1.25-1.93). Follow-up in the first year was 71 %
      and no case of severe or recurrent hypothyroidism was detected. CONCLUSIONS:
      Surgery without general anesthesia performed in a nonhospital setting in
      underdeveloped countries in patients with goiter is a viable option with good
      results and low morbidity.

PMID- 24728538
TI  - The rice restorer Rf4 for wild-abortive cytoplasmic male sterility encodes a
      mitochondrial-localized PPR protein that functions in reduction of WA352
      transcripts.

PMID- 24728539
TI  - On deep history and pyschotropy.

PMID- 24728537
TI  - Relevance of surgery after embolization of gastrointestinal and abdominal
      hemorrhage.
AB  - BACKGROUND: Gastrointestinal and abdominal bleeding can lead to life-threatening
      situations. Embolization is considered a feasible and safe treatment option. The
      relevance of surgery has thus diminished in the past. The aim of the present
      study was to evaluate the role of surgery in the management of patients after
      embolization. METHODS: We performed a retrospective single-center analysis of
      outcomes after transarterial embolization of acute abdominal and gastrointestinal
      hemorrhage between January 2009 and December 2012 at the Sisters of Charity
      Hospital, Linz. Patients were divided into three groups, as follows: upper
      gastrointestinal bleeding (UGIB), lower gastrointestinal bleeding (LGIB), and
      abdominal hemorrhage. RESULTS: Fifty-four patients with 55 bleeding events were
      included. The bleeding source could be localized angiographically in 80 %, and
      the primary clinical success rate of embolization was 81.8 % (45/55 cases). Early
      recurrent bleeding (<30 days) occurred in 18.2 % (10/55) of the patients, and
      delayed recurrent hemorrhage (>30 days) developed in 3.6 % (2/55). The mean
      follow-up was 8.4 months, and data were available for 85.2 % (46/54) of the
      patients. Surgery after embolization was required in 20.4 % of these patients
      (11/54). Failure to localize the bleeding site was identified as predictive of
      recurrent bleeding (p = 0.009). More than one embolization effort increased the
      risk of complications (p = 0.02) and rebleeding (p = 0.07). CONCLUSIONS: Surgery
      still has an important role after embolization in patients with gastrointestinal
      and abdominal hemorrhage. One of five patients required surgery in cases of early
      and delayed rebleeding or because of ischemic complications (2/55 both had
      ischemic damage of the gallbladder) and bleeding consequences.

PMID- 24728540
TI  - Efficient and exceptionally selective semireduction of alkynes using a supported
      gold catalyst under a CO atmosphere.
AB  - A new efficient method for chemo- and regio-selective semireduction of alkynes
      using CO/H2O as the hydrogen source catalyzed by gold supported on high surface
      area TiO2 was developed. A facile and practical synthesis of 1,2
      dideuterioalkenes was also realized by using CO/D2O as the reducing agent. 

PMID- 24728541
TI  - Advancing pharmacy practice through scholarship while engaging student
      pharmacists during early didactic training.

PMID- 24728542
TI  - Cost-effectiveness of modern mTOR inhibitor based immunosuppression compared to
      the standard of care after renal transplantation in Germany.
AB  - OBJECTIVES: Standards of immunosuppression in renal transplantation have changed
      dynamically in recent years. We here provide a refined advanced pharmacoeconomic
      model which uses state-of-the-art methods including a mixed treatment comparison
      (MTC) analysis. The aim was to assess the cost-effectiveness of current
      immunosuppressive therapy regimens (TR): "sirolimus + early withdrawal of
      cyclosporine + steroids" (TR1), "sirolimus-early transition" (TR2), "everolimus
      early transition" (TR3) and "tacrolimus low dose + mycophenolate mofetil (MMF) +
      steroids" (TR4). METHODS: An up-to-date Markov model with current source data was
      employed to assess the cost-effectiveness of modern immunosuppressive regimens
      over 12-month and 10-year time periods. Transition probabilities for the
      occurrence of events for the first year were based on an MTC analysis. The
      robustness of the model was tested in extensive sensitivity analyses. RESULTS:
      Within the 12-month time period TR2 yields the highest life years (0.987 LY),
      generating costs of 17,500 <euro>. In terms of years with functioning graft (FG),
      TR4 yields the best efficacy over the 12-month model duration (0.970 years with
      FG). For the 10-year time period, TR2 yields the lowest costs (107,246 <euro>)
      and dominates both TR3 and TR1, as it is simultaneously more effective. Within
      the 10-year model duration, TR4 reaches slightly higher effects compared with TR2
      (6.493 vs. 6.474 LY) resulting in an incremental cost-effectiveness ratio of
      387,684 <euro> per LY gained. CONCLUSIONS: The early transition to sirolimus
      provides long-term efficiency results comparable with a tacrolimus-based regimen,
      which represents a common treatment standard after kidney transplantation. Both
      are superior to other investigated immunosuppressive regimens.

PMID- 24728543
TI  - The influence of SBR parameters on the sludge toxicity of synthetic wastewater
      containing bisphenol A.
AB  - Synthetic wastewater with bisphenol A (BPA) concentrations of 7.5, 20, and 40
      mg/L was treated with activated sludge sequential batch reactors (SBRs). The
      sludge acute toxicity indicated by the inhibitory ratio to luminous bacteria T3
      was evaluated. The influent COD was controlled at approximately 300 mg/L, and
      aerobic conditions were maintained in the SBR. It was found that the process of
      BPA biodegradation, as opposed to BPA adsorption, contributed to the formation of
      sludge toxicity; there was a positive relationship between sludge toxicity and
      influent BPA concentration, and the toxicity centralized in intracellular regions
      and the intersection of extracellular polymeric substances (EPS) in sludge flocs.
      Since the BPA biodegradation process dedicated to sludge toxicity, the influence
      of key operational parameters such as sludge retention time (SRT) and hydraulic
      retention time (HRT) on sludge toxicity were investigated. It was founded that
      sludge toxicity decreased significantly when SRT and HRT were shortened from 20
      to 10 days and 12 to 8 h, respectively. The results of Pearson correlation
      analysis indicated that the Shannon index H of the bacterial community correlated
      significantly to sludge toxicity. The results from both similarity analysis and
      UPGMA indicated that influent quality characteristic contributes much more to
      bacterial community than operation parameters, and then leads to difference
      between blank and control sludge toxicity. 

PMID- 24728545
TI  - Synthesis and characterization of germa[n]pericyclynes.
AB  - The synthesis and characterization of novel pericyclynes comprising germanium
      atoms and acetylenes, germa[n]pericyclynes, are described. The prepared germa[4]
      , [6]-, and [8]pericyclynes were compared by (13)C NMR spectroscopy, X-ray
      crystallography, cyclic voltammetry, UV-visible spectroscopy, fluorescence
      emission spectroscopy, Raman spectroscopy, and density functional theory
      calculation analyses. 

PMID- 24728544
TI  - Monitoring endocrine disrupting compounds and estrogenic activity in tap water
      from Central Spain.
AB  - The aims of this study are to investigate the presence of 30 substances known or
      thought to act as endocrine disrupting compounds in tap water from the main water
      supply areas for region of Madrid, to determine the total estrogenic activity of
      the samples analysed and to estimate the health risk for the population resulting
      from those compounds found at detectable concentrations. To this end, a one-off
      composite sampling was performed in August 2012 in which six tap water samples
      were collected from private residences in the drinking water supply network of
      the region of Madrid. A total of 14 of the 30 endocrine disruptors analysed were
      found at concentrations ranging from 0.3 to 165 ng/L. The organophosphorus flame
      retardants were detected at the highest concentrations followed by the
      plasticizer bisphenol A, alkylphenols, anticorrosion agents and preservatives.
      Tap water in the region of Madrid is contaminated with traces (ng/L) of compounds
      with endocrine disrupting properties. Although the concentrations of endocrine
      disrupting compounds obtained are too low to be able to confirm a public health
      risk, and no risk has been detected upon evaluation, it should be remembered that
      these compounds act at very low doses and that their effects may only appear in
      the long term. 

PMID- 24728546
TI  - From positive emotionality to internalizing problems: the role of executive
      functioning in preschoolers.
AB  - Temperament and psychopathology are intimately related; however, research on the
      prospective associations between positive emotionality, defined as a child's
      positive mood states and high engagement with the environment, and
      psychopathology is inconclusive. We examined the longitudinal relation between
      positive emotionality and internalizing problems in young children from the
      general population. Furthermore, we explored whether executive functioning
      mediates any observed association. Within a population-based Dutch birth cohort,
      we observed positive emotionality in 802 children using the laboratory
      temperament assessment battery at age 3 years. Child behavior checklist (CBCL)
      internalizing problems (consisting of Emotionally Reactive, Anxious/Depressed,
      and Withdrawn scales) were assessed at age 6 years. Parents rated their
      children's executive functioning at ages 4 years. Children with a lower positive
      emotionality at age 3 had a higher risk of withdrawn problems at age 6 years (OR
      = 1.20 per SD decrease in positive emotionality score, 95 % CI: 1.01, 1.42). This
      effect was not explained by preexisting internalizing problems. This association
      was partly mediated by more problems in the shifting domain of executive
      functioning (p < 0.001). We did not find any relation between positive
      emotionality and the CBCL emotionally reactive or anxious/depressed scales.
      Although the effect sizes were moderate, our results suggest that low levels of
      positive emotionality at preschool age can result in children's inflexibility and
      rigidity later in life. The inflexibility and rigidity are likely to affect the
      child's drive to engage with the environment, and thereby lead to withdrawn
      problems. Further research is needed to replicate these findings.

PMID- 24728547
TI  - Bleeding Complications After PCI and the Role of Transradial Access.
AB  - OPINION STATEMENT: Bleeding events are the most common complications following
      percutaneous coronary intervention (PCI) and are associated with increases in
      short- and long-term mortality, nonfatal myocardial infarction, stroke, hospital
      length of stay, and hospital cost. Over time, there has been a decrease in
      periprocedural bleeding, primarily due to improvements in antithrombotic therapy;
      however, transradial (TR) catheterization has been shown to be an important
      strategy to minimize access site bleeding and potentially improve outcomes among
      patients with ST-segment elevation myocardial infarction. The rate of TR
      catheterization has been increasing significantly over the past few years and now
      accounts for an increasing proportion of procedures performed in the United
      States. Results from the recently published RIVAL Trial have shown comparable
      efficacy between transradial and transfemoral (TF) approaches with significant
      reduction in vascular access complications in the TR group. TR access in the
      STEMI population was prospectively assessed in the RIFLE-STEACS Trial and
      demonstrated significant reduction in the primary outcome of composite
      death/MI/stroke/target vessel revascularization/non-CABG bleeding. More recent
      studies have also demonstrated cost savings with TR access, related primarily to
      decreased hospital length of stay. While previous studies have shown increased
      operator radiation exposure compared to a TF approach, the most recent data
      suggest no significant difference in radiation at higher volume centers.

PMID- 24728548
TI  - Non-invasive assessment of carotid PWV via accelerometric sensors: validation of
      a new device and comparison with established techniques.
AB  - PURPOSE: Carotid pulse wave velocity (PWV) is considered as a surrogate marker
      for carotid stiffness and its assessment is increasingly being used in clinical
      practice. However, at the moment, its estimation needs specific equipment and a
      moderate level of technical expertise; moreover, it is based on a mathematical
      model. The aim of this study was to validate a new system for non-invasive and
      model-free carotid PWV assessment based on accelerometric sensors by comparison
      with currently used techniques. METHODS: Accelerometric PWV (accPWV) values were
      obtained in 97 volunteers free of cardiovascular disease (age 24-85 years) and
      compared with standard ultrasound-based carotid stiffness parameters, such as
      carotid PWV (cPWV), relative distension (relD) and distensibility coefficient
      (DC). Moreover, the comparison between accPWV measurements and carotid-femoral
      PWV (cfPWV) was performed. RESULTS: Accelerometric PWV evaluations showed a
      significant correlation with cPWV measurements (R = 0.67), relD values (R = 0.66)
      and DC assessments (R = 0.64). These values were also significantly correlated
      with cfPWV evaluations (R = 0.46). In addition, the first attempt success rate
      was equal to 76.8 %. CONCLUSIONS: The accelerometric system allows a simple and
      quick local carotid stiffness evaluation and the values obtained with this system
      are significantly correlated with known carotid stiffness biomarkers. Therefore,
      the presented device could provide a concrete opportunity for an easy carotid
      stiffness evaluation even in clinical practice.

PMID- 24728549
TI  - Viscoelasticity of nematic liquid crystals at a glance.
AB  - Polarised microscopy is shown to be a powerful alternative to light scattering
      for the determination of the viscoelasticity of aligned nematic liquid crystals.
      We perform experiments in a wide range of temperatures by using an adapted
      version of the recently introduced differential dynamic microscopy technique,
      which enables us to extract scattering information directly from the microscope
      images. A dynamic analysis of the images acquired in different geometries
      provides the splay, twist and bend viscoelastic ratios. A static analysis allows
      a successful determination of the bend elastic constant. All our results are in
      excellent agreement with those obtained with the far more time-consuming
      depolarised light scattering techniques. Remarkably, a noteworthy extension of
      the investigated temperature-range is observed, owing to the lower sensitivity of
      microscopy to multiple scattered light. Moreover, we show that the unique space
      resolving capacities of our method enable us to investigate nematics in the
      presence of spatial disorder, where traditional light scattering fails. Our
      findings demonstrate that the proposed scattering-with-images approach provides a
      space-resolved probe of the local sample properties, applicable also to other
      optically anisotropic soft materials. 

PMID- 24728550
TI  - [Not Available].

PMID- 24728552
TI  - [Not Available].

PMID- 24728551
TI  - [Not Available].

PMID- 24728553
TI  - [Not Available].

PMID- 24728554
TI  - [Not Available].

PMID- 24728555
TI  - Tree growth response to ENSO in Durango, Mexico.
AB  - The dynamics of forest ecosystems worldwide have been driven largely by climatic
      teleconnections. El Nino-Southern Oscillation (ENSO) is the strongest interannual
      variation of the Earth's climate, affecting the regional climatic regime. These
      teleconnections may impact plant phenology, growth rate, forest extent, and other
      gradual changes in forest ecosystems. The objective of this study was to
      investigate how Pinus cooperi populations face the influence of ENSO and regional
      microclimates in five ecozones in northwestern Mexico. Using standard
      dendrochronological techniques, tree-ring chronologies (TRI) were generated. TRI,
      ENSO, and climate relationships were correlated from 1950-2010. Additionally,
      multiple regressions were conducted in order to detect those ENSO months with
      direct relations in TRI (p < 0.1). The five chronologies showed similar trends
      during the period they overlapped, indicating that the P. cooperi populations
      shared an interannual growth variation. In general, ENSO index showed
      correspondences with tree-ring growth in synchronous periods. We concluded that
      ENSO had connectivity with regional climate in northern Mexico and radial growth
      of P. cooperi populations has been driven largely by positive ENSO values (El
      Nino episodes).

PMID- 24728556
TI  - Prevalence of Rickettsiales (Anaplasma phagocytophilum and Rickettsia spp.) in
      hard ticks (Ixodes ricinus) in the city of Hamburg, Germany.
AB  - To narrow the gap of missing knowledge on Rickettsia spp. and Anaplasma
      phagocytophilum infections in ticks in northwestern Germany and, at the same
      time, to provide first prevalence data on these pathogens in the city of Hamburg,
      a total of 1,400 questing Ixodes ricinus ticks were collected at ten different
      public green areas from April until October 2011. Ticks were examined using probe
      based quantitative real-time PCR. A percentage of 3.6% (51/1,400) ticks were
      tested positive for A. phagocytophilum infections divided into 2.1% (3/141)
      adults [1.7% (1/60) females and 2.5% (2/81) males] and 3.8% (48/1,259) nymphs.
      The percentage of infected ticks per sampling site varied statistically
      significantly from 0.7% (1/140) to 12.1% (17/140), whereas between sampling
      months, no statistically significant differences were observed (2.0-6.5%, 4
      13/140). The overall Rickettsia spp. infection rate was 52.5% (735/1,400). In
      adult ticks, Rickettsia spp. infection rate was 56% (79/141) divided into 61.7%
      (37/60) infected females and 51.9% (42/81) infected males. Nymphs showed an
      infection rate of 52.1% (656/1,259). In contrast to A. phagocytophilum
      infections, no statistically significant differences in Rickettsia spp. infection
      rates among sampling sites (44.3-63.6%, 62-89/140) were observed, whereas
      seasonal variations were obvious: the percentage of Rickettsia-positive ticks was
      significantly lower in April (36.5%, 73/200) and May (29.5%, 59/200) compared to
      the summer and fall months (55.0-64.5%, 110-129/200). Rickettsia species
      differentiation via real-time pyrosequencing revealed Rickettsia helvetica as the
      only occurring species. Co-infections with both Rickettsia spp. and A.
      phagocytophilum were detected in 2.0% (28/1,400) of the ticks. The present study
      revealed that in the city of Hamburg, the tick infection rate with A.
      phagocytophilum is comparable with other German data, whereas the Rickettsia spp.
      infection rate of 52.5% is by far the highest prevalence detected in Germany so
      far. As the city of Hamburg has 1.8 million inhabitants and attracts millions of
      tourists every year, the potential health risk should not be underestimated.

PMID- 24728557
TI  - Molecular characterization of five widespread avian haemosporidian parasites
      (Haemosporida), with perspectives on the PCR-based detection of haemosporidians
      in wildlife.
AB  - Haemosporidians (Haemosporida) are cosmopolitan in birds. Over 250 species of
      these blood parasites have been described and named; however, molecular markers
      remain unidentified for the great majority of them. This is unfortunate because
      linkage between DNA sequences and identifications based on morphological species
      can provide important information about patterns of transmission, virulence, and
      evolutionary biology of these organisms. There is an urgent need to remedy this
      because few experts possess the knowledge to identify haemosporidian species and
      few laboratories are involved in training these taxonomic skills. Here, we
      describe new mitochondrial cytochrome b markers for the polymerase chain reaction
      (PCR)-based detection of four widespread species of avian Haemoproteus
      (Haemoproteus hirundinis, Haemoproteus parabelopolskyi, Haemoproteus pastoris,
      Haemoproteus syrnii) and 1 species of Plasmodium (Plasmodium circumflexum).
      Illustrations of blood stages of the reported species are given, and
      morphological and phylogenetic analyses identify the DNA lineages that are
      associated with these parasites. This study indicates that morphological
      characters, which have been traditionally used in taxonomy of avian
      haemosporidian parasites, have a phylogenetic value. Perspectives on
      haemosporidian diagnostics using microscopic and PCR-based methods are discussed,
      particularly the difficulties in detection of light parasitemia, coinfections,
      and abortive parasite development. We emphasize that sensitive PCR amplifies more
      infections than can be transmitted; it should be used carefully in epidemiology
      studies, particularly in wildlife parasitology research. Because molecular
      studies are describing remarkably more parasite diversity than previously
      expected, the need for traditional taxonomy and traditional biological knowledge
      is becoming all the more crucial. The linkage of molecular and morphological
      approaches is worth more of the attention of researchers because this approach
      provides new knowledge for better understanding insufficiently investigated
      lethal diseases caused by haemosporidian infections, particularly on the
      exoerythrocytic (tissue) and vector stages. That requires close collaboration
      between researchers from different fields with a common interest. 

PMID- 24728558
TI  - Vaccination with Toxoplasma lysate antigen and CpG oligodeoxynucleotides:
      comparison of immune responses in intranasal versus intramuscular
      administrations.
AB  - Toxoplasma gondii (T. gondii) is one of the most successful intracellular
      protozoan parasites on earth and highly prevalent in most warm-blooded
      vertebrates. There are no drugs that target the chronic cyst stage of this
      infection; therefore, development of an effective vaccine would be an important
      advance in disease control. Oligodeoxynucleotides (ODN) which contain
      immunostimulatory CG motifs (CpG ODN) can promote T-helper 1 (Th1) responses, an
      adjuvant activity that is desirable for vaccination against intracellular
      pathogen. In this study, we compare the immune responses of Toxoplasma
      susceptible C57BL/6 mice following intranasal and intramuscular vaccination with
      Toxoplasma lysate antigen (TLA) with or without CpG ODN as adjuvant. Immunized
      and control non-immunized mice were challenged with 85 cyst of the moderately
      virulent Beverley strain of T. gondii. Intranasal vaccination gave significantly
      a higher protection compared to other groups as indicated by prolonged survival
      and significantly reduced brain cyst burden (P < 0.01). Intranasal vaccination
      stimulated cellular immunity towards Th1 response characterized by significant
      INF-gamma production (P < 0.01). Furthermore, fecal IgA antibody levels as an
      indicator of mucosal immune responses were significantly higher (P < 0.05) in
      intranasal vaccinated group before the challenge compared to all other groups.
      Intranasal vaccination was not able to upgrade the Th1 humoral arm. In contrast,
      intramuscular vaccination enhanced humoral immunity towards a type Th1 pattern
      characterized by a significant increase of specific IgG and Ig2a. Our results
      suggest that intranasal administration of CpG/TLA would provide a stable,
      pronounced, and effective vaccine against toxoplasmosis through stimulation of
      Th1 cellular immunity and mucosal IgA. 

PMID- 24728559
TI  - Comparison of calculation methods used for the determination of anthelmintic
      resistance in sheep in a temperate continental climate.
AB  - This study compared results obtained with five different fecal egg count
      reduction (FECR) calculation methods for defining resistance to ivermectin,
      fenbendazole, and levamisole in gastrointestinal nematodes of sheep in a
      temperate continental climate: FECR1 and FECR2 used pre- and posttreatment fecal
      egg count (FEC) means from both treated and control animals, but FECR1 used
      arithmetic means, whereas FECR2 used geometric means; FECR3 used arithmetic means
      for pre- and posttreatment FECs from treated animals only; FECR4 was calculated
      using only arithmetic means for posttreatment FECs from treated and control
      animals; and FECR5 was calculated using mean FEC estimates from a general linear
      mixed model. The classification of farm anthelmintic resistance (AR) status
      varied, depending on which FECR calculation method was used and whether a bias
      correction term (BCT, i.e., half the minimum detection limit) was added to the
      zeroes or not. Overall, agreement between all methods was higher when a BCT was
      used, particularly when levels of resistance were low. FECR4 showed the highest
      agreement with all the other FECR methods. We therefore recommend that small
      ruminant clinicians use the FECR4 formula with a BCT for AR determination, as
      this would reduce the cost of the FECRT, while still minimizing bias and allowing
      for comparisons between different farms. For researchers, we recommend the use of
      FECR1 or FECR2, as the inclusion of both pre- and posttreatment FECs and use of
      randomly allocated animals in treatment and control groups makes these methods
      mathematically more likely to estimate the true anthelmintic efficacy. 

PMID- 24728561
TI  - H(2) production through electro-oxidation of SO(2): identifying the fundamental
      limitations.
AB  - Sulphur dioxide (SO2), a known industrial pollutant and pulmonary irritant, is
      emitted to the atmosphere in excess of 120 Mt per annum. Great strides have been
      taken to reduce SO2 emissions, but with the growth of specifically China, and to
      a lesser extent India, it is on the rise again. The electrolysis of aqueous
      solutions of dissolved SO2 holds huge environmental potential in that SO2 is
      converted to sulphuric acid (H2SO4) and at the same time hydrogen gas is
      produced. A further benefit or incentive is that a sulphur depolarised
      electrolyser (SDE) operates at an applied potential that is about one volt lower
      than that of a regular water electrolyser. In taking this technology forward the
      greatest improvement to be made is in developing a suitable electrocatalyst,
      which is also the 'lowest hanging fruit' in that very limited research and
      development has been conducted on the electrocatalyst for this process. In this
      work, density functional theory is employed to model the electro-oxidation of SO2
      on single crystal planes of the 4d and 5d transition metals. Two reaction
      mechanisms are considered, a HSO3 intermediate pathway and a SO3 intermediate
      pathway. The binding energies of all intermediates are found to scale with the
      surface reactivity (measured as the adsorption of OH). Irrespective of the
      pathway water needs to be activated and reduction of SO2 to elemental sulphur
      must be avoided. This requirement alone calls for an electrode potential of at
      least 0.7-0.8 V for all the investigated transition metals and thus challenges
      the proclaimed goal to operate the SDE at 0.6 V. A high chemical barrier is
      further found to severely limit the oxidation reaction on reactive metals. A much
      higher catalytic activity can be obtained on precious metals but at the cost of
      running the reaction at high overpotentials. 

PMID- 24728560
TI  - The interaction of aurein 2.5 with fungal membranes.
AB  - Aurein 2.5 (GLFDIVKKVVGAFGSL-NH2) is an antimicrobial peptide, which was seen to
      have activity against Stachybotris chartarum, Penicillium roseopurpureum and
      Aspergillus flavus with minimum fungicidal concentrations in the range 250-500
      MUM. S. chartarum showed enhanced susceptibility to lysis as compared to P.
      roseopurpureum and A. flavus, (44, 26 and 28 % respectively). Monolayers formed
      from lipid membrane extracts derived from S. chartarum, P. roseopurpureum and A.
      flavus showed maximal surface pressure changes of 13.5, 10.3 and 10.2 mN m(-1)
      respectively. However, aurein 2.5 adopted similar levels of alpha-helical
      structure (circa 45 %) in the presence of vesicles formed from membrane lipid
      extracts derived from all three fungi. These data imply that differential
      activity is not due to targeting and membrane association but linked to the
      ability of the bound peptide to lyse the cells. At sterol levels mimetic of
      eukaryotic systems, high levels of alpha-helical structure (circa 50 %) were also
      observed and hence similar binding. However, enhanced sterol levels (>0.6) led to
      a reduction in monolayer membrane interaction, suggesting that the sterols
      influence efficacy. Consistent with this suggestion, thermodynamic analysis
      showed that the peptide was able to destabilise model fungal monolayers, as
      indicated by negative values of ?Gmix.

PMID- 24728562
TI  - Tunable light emission from co-assembled structures of benzothiadiazole
      molecules.
AB  - Co-assembled structures possessing tunable light emission from 510-690 nm have
      been prepared using various compositions of two different 4,7-substituted
      benzothiadiazole molecules, 1 and 2. The preferential incorporation and co
      localization of 1 and 2 to produce co-assemblies are possible because of
      structural similarities and allow for tuning of morphology and light emission.

PMID- 24728563
TI  - Pharmacist demand and the need for expanded postgraduate training.

PMID- 24728564
TI  - Association between single nucleotide polymorphisms (SNPs) of XRCC2 and XRCC3
      homologous recombination repair genes and triple-negative breast cancer in Polish
      women.
AB  - XRCC2 and XRCC3 genes involved in homologous recombination repair (HRR) of DNA
      and in the maintenance of the genome integrity play a crucial role in protecting
      against mutations that lead to cancer. The aim of the present work was to
      evaluate associations between the risk of triple-negative breast cancer (TNBC)
      and polymorphisms in the genes, encoding for two key proteins of HRR: XRCC2
      Arg188His (c. 563 G>A; rs3218536, Genbank Accession Number NT 007914) and XRCC3
      Thr241Met (c. 722 C>T; rs861539, Genbank Accession Number NT 026437). The
      polymorphisms of the XRCC2 and XRCC3 were investigated by PCR-RFLP in 70 patients
      with TNBC and 70 age- and sex-matched non-cancer controls. In the present work, a
      relationship was identified between XRCC2 Arg188His polymorphism and the
      incidence of triple-negative breast cancer. The 188His allele and 188His/His
      homozygous variant increased cancer risk. An association was confirmed between
      XRCC2 Arg188His and XRCC3 Thr241Met polymorphisms and TNBC progression, assessed
      by the degree of lymph node metastases and histological grades. In conclusion,
      XRCC2 Arg188His and XRCC3 Thr241Met polymorphisms may be regarded as predictive
      factors of triple-negative breast cancer in female population.

PMID- 24728565
TI  - Uncovering the pathogenesis and identifying novel targets of pancreatic cancer
      using bioinformatics approach.
AB  - Pancreatic cancer is a uniformly lethal disease that can be difficult to diagnose
      at its early stage. Thus, our present study aimed to explore the underlying
      mechanism and identify new targets for this disease. The data GSE16515, including
      36 tumor and 16 normal samples were available from Gene Expression Omnibus.
      Differentially expressed genes (DEGs) were screened out using Robust Multichip
      Averaging and LIMMA package. Moreover, gene ontology and pathway enrichment
      analyses were performed to DEGs. Followed with protein-protein interaction (PPI)
      network construction by STRING and Cytoscape, module analysis was conducted using
      ClusterONE. Finally, based on PubMed, text mining about these DEGs was carried
      out. Total 274 up-regulated and 93 down-regulated genes were identified as the
      common DEGs and these genes were discovered significantly enriched in cell
      adhesion and extracellular region terms, as well as ECM-receptor interaction
      pathway. In addition, five modules were screened out from the up-regulated PPI
      network with none in down-regulated network. Finally, the up-regulated genes,
      including MIA, MET and CEACAMS, and down-regulated genes, such as FGF, INS and
      LAPP, had the most references in text mining analysis. Our findings demonstrate
      that the up- and down-regulated genes play important roles in pancreatic cancer
      development and might be new targets for the therapy. 

PMID- 24728566
TI  - Identification of a novel mutation of the gene for gap junction protein alpha3
      (GJA3) in a Chinese family with congenital cataract.
AB  - Cataract, defined as any opacity of the crystallin lens, can be divided into
      early onset (congenital or infantile) and age-related. It is the leading cause of
      visual disability in children, and mutations in many genes have currently been
      linked with this disorder. In the present study, we identified a genetic defect
      in a Chinese family with congenital cataract. Genomic DNA was extracted from the
      venous blood of the family and 100 normal controls. To screen for the disease
      causing mutation, we sequenced eight candidate genes, and to predict the
      functional consequences of the mutation, a structural model of the protein was
      developed using the Protein Data Bank and PyMOL 1.1r1. We found a novel variant
      (c.163 A > G transition) in the gene for gap junction protein alpha3, or the
      connexin46 gene. This mutation resulted in the substitution of a highly conserved
      asparagine at codon 55 by aspartic acid (p.N55D). There were no nucleotide
      polymorphisms in the other candidate genes sequenced.

PMID- 24728567
TI  - Computational identification of novel microRNAs and targets in Glycine max.
AB  - Plant miRNAs, the endogenous non-coding small RNAs of about 20-24 nucleotides,
      play important roles in multiple biological processes by acting as negative
      regulators of their targeted mRNAs. Soybean (Glycine max (L.) Merr.) is one of
      the important oil crops of the world, in which many miRNAs have been obtained
      through the computational prediction or experiments. However, the miRNA genes
      identified for soybean are still far from saturation, and their biological
      functions are largely unknown. Here, a total of 48 candidates of miRNAs were
      identified following a range of strict filtering criteria. Detailed sequence
      analysis showed that G. max pre-miRNAs vary in length from 47 to 380 nt, embody
      mature miRNAs that differ in their physical location within the pre-miRNAs. In
      this study, twenty miRNAs were confirmed by microarray and three miRNAs were
      further validated by poly(A)-tailed RT-PCR. Comparative sequence analysis of
      soybean miRNA sequences showed that uracil is the dominant base in the first
      position at the 5' end of the mature miRNAs, and the base may have an important
      functional role in miRNA biogenesis and/or miRNA-mediated gene regulation.
      Finally, we predicted potential targets of these miRNAs. These target genes were
      predicted to encode transcription factors, resistance protein, heat shock
      protein, protein kinase, transporter, zinc finger protein and others, which might
      play important roles in soybean development and stress response. 

PMID- 24728568
TI  - Characterization of the expression profile of CRBP1 and CRBP3 gene in chicken.
AB  - In this study, we quantified the expression of CRBP1 and CRBP3 in Roman layer (R)
      and Erlang mountainous chickens (SD02 and SD03), to discern the tissue, breed and
      age-related expression patterns in order to discover potential involvement in egg
      production and other related reproduction traits. Real-time quantitative PCR
      assays were developed for accurate measurement of CRBP1 and CRBP3 mRNA levels in
      different tissues from chickens at four ages (12, 20, 32 and 45 weeks). We found
      that the CRBP1 and CRBP3 were expressed in all six tissues examined in all three
      breeds of chicken at 32 weeks. CRBP1 mRNA levels in SD02 kidneys were slightly
      higher than those in SD03 and R at 12 weeks, whereas, at the other three time
      points, the expression levels of CRBP1 in SD03 were higher than those in SD02 and
      R. In addition, there was higher hepatic expression of CRBP3 mRNA in layers (R)
      compared to broilers (SD02 and SD03) at 20 and 32 weeks. An age-related
      expression pattern of CRBP1 gene was evident in liver (P < 0.01), but not in
      pituitary (P > 0.05). Overall, the expression level of CRBP1 gene in kidney,
      ovary and oviduct at the different ages had a "decline-rise-decline" trend in all
      three breeds. In contrast, in pituitary, hypothalamus, liver and kidney CRBP3
      mRNA expression levels were significantly different at various ages (P < 0.05)
      and exhibited a "rise-decline-rise" pattern in all three breeds. Our results show
      that the expression of CRBP1 and CRBP3 in chicken tissues exhibit specific
      developmental changes and age-related patterns.

PMID- 24728569
TI  - Molecular analysis of testis biopsy and semen pellet as complementary methods
      with histopathological analysis of testis in non-obstructive azoospermia.
AB  - PURPOSE: Non-obstructive azoospermia (NOA) is one the many causes of male
      infertility (10 %) resulting from testicular failure. Multiple testicular
      biopsies fail to find mature sperm in at least 50 % of cases Therefore; hunting
      for sensitive and specific biomarkers of spermatogenesis that could better
      determine the fertility status in NOA can lead to improved management of male
      infertility. Therefore, we evaluated sperm production through analyses of germ
      cell-specific transcripts (DAZ, TSPY1, SPTRX3 and SPTRX1) in semen and testicular
      biopsies of men with azoospermia. METHODS: We collected semen (N=83) and testis
      biopsies (N=31) from men with non-obstructive azoospermia. We later extracted RNA
      and synthesized cDNA using washed semen precipitate and testicular tissues. We
      also performed semi-nested PCR with designed specific primers. Using H&E method,
      an expert pathologist performed the histopathological evaluation. Having
      categorized the patients into three groups based on histopathological results, we
      calculated the agreement between molecular results of semen and tissues with
      histopathological findings for each patient using Kappa statistical test.
      RESULTS: Molecular findings of precipitated semen and testicular tissues were in
      disagreement with histopathological results in most cases. Molecular analysis of
      testis biopsies showed significant difference (Kappa coefficient=0.009, P
      value=0.894) with histopathological results; TSPY1, DAZ, SPTRX3 and SPTRX1 were
      respectively detected in 94 %, 94 %, 17.6 % and 52.9 % of men diagnosed with germ
      cell aplasia. CONCLUSIONS: Molecular analysis of semen does not provide
      sufficient sensitivity and specificity to be used as a screening test at the
      present time, but it is a useful adjunct to histopathological methods in men with
      NOA. Spermatid/sperm specific transcripts indicated the possibility to find
      mature sperm following repeated multiple testicular sperm extraction (TESE) or
      microdisection TESE (mTESE).

PMID- 24728570
TI  - Characterization of carbonaceous aerosols over Delhi in Ganga basin: seasonal
      variability and possible sources.
AB  - The mass concentration of carbonaceous species, organic carbon (OC), and
      elemental carbon (EC) using a semicontinuous thermo-optical EC-OC analyzer, and
      black carbon (BC) using an Aethalometer were measured simultaneously at an urban
      mega city Delhi in Ganga basin from January 2011 to May 2012. The concentrations
      of OC, EC, and BC exhibit seasonal variability, and their concentrations were ~2
      times higher during winter (OC 38.1 +/- 17.9 MUg m(-3), EC 15.8 +/- 7.3 MUg m(
      3), and BC 10.1 +/- 5.3 MUg m(-3)) compared to those in summer (OC 14.1 +/- 4.3
      MUg m(-3), EC 7.5 +/- 1.5 MUg m(-3), and BC 4.9 +/- 1.5 MUg m(-3)). A significant
      correlation between OC and EC (R = 0.95, n = 232) indicate their common emission
      sources with relatively lower OC/EC ratio (range 1.0-3.6, mean 2.2 +/- 0.5)
      suggests fossil fuel emission as a major source of carbonaceous aerosols over the
      station. On average, mass concentration of EC was found to be ~38 % higher than
      BC during the study period. The measured absorption coefficient (babs) was
      significantly correlated with EC, suggesting EC as a major absorbing species in
      ambient aerosols at Delhi. Furthermore, the estimated mass absorption efficiency
      (sigmaabs) values are similar during winter (5.0 +/- 1.5 m(2) g(-1)) and summer
      (4.8 +/- 2.8 m(2) g(-1)). Significantly high aerosol loading of carbonaceous
      species emphasize an urgent need to focus on air quality management and proper
      impact assessment on health perspective in these regions.

PMID- 24728571
TI  - Electrosorption and photocatalytic one-stage combined process using a new type of
      nanosized TiO2/activated charcoal plate electrode.
AB  - In the present study, an activated charcoal (AC) plate was prepared by physical
      activation method. Its surface was coated with TiO2 nanoparticles by
      electrophoretic deposition (EPD) method. The average crystallite size of TiO2
      nanoparticles was determined approximately 28 nm. The nature of prepared
      electrode was characterized by X-ray diffraction (XRD), scanning electron
      microscopy (SEM), and Brunauer-Emmett-Teller (BET) surface area measurement
      before and after immobilization. The electrosorption and photocatalytic one-stage
      combined process was investigated in degradation of Lanasol Red 5B (LR5B), and
      the effect of dye concentration, electrolyte concentration, pH, voltage, and
      contact time was optimized and modeled using response surface methodology (RSM)
      approach. The dye concentration of 30 mg L(-1), Na2SO4 concentration of 4.38 g L(
      1), pH of 4, voltage of 250 mV, and contact time of 120 min were determined as
      optimum conditions. Decolorization efficiency increased in combined process to
      85.65% at optimum conditions compared to 66.03% in TiO2/AC photocatalytic, 20.09%
      in TiO2/AC electrosorption, and 1.91% in AC photocatalytic processes.

PMID- 24728572
TI  - The adsorption process during inorganic phosphorus removal by cultured
      periphyton.
AB  - To explain the detailed process involved in phosphorus removal by periphyton, the
      periphyton dominated by photoautotrophic microorganisms was employed in this
      study to remove inorganic phosphorus (Pi) from wastewater, and the removal
      kinetics and isotherms were then evaluated for the Pi removal process. Results
      showed that the periphyton was capable of effectively removing Pi that could
      completely remove the Pi in 24 h at an initial Pi concentration of 13 mg P L(-1).
      Furthermore, the Pi removal process by the periphyton was dominated by adsorption
      at initial stage (~24 h), which involved physical mechanistic process. However,
      this Pi adsorption process was significantly influenced by environmental
      conditions. This work provides an insight into the understanding of phosphorus
      adsorption by periphyton or similar microbial aggregates.

PMID- 24728573
TI  - Characterization of springtime airborne particulate matter-bound reactive oxygen
      species in Beijing.
AB  - Epidemiologic studies have suggested that particulate matter (PM)-associated
      adverse health effects are related to particle composition. To study the
      toxicological characteristics of dust storm, airborne PM10 was collected at two
      sites in Beijing from March to May 2012. The production of reactive oxygen
      species (ROS), quantified by dithiothreitol (DTT), was used to measure the PM
      induced oxidative potential. Two dust storm (DS) samples were monitored during
      the sampling period: one happened on March 28th (DS1) and the other one was on
      April 28th (DS2). The backward trajectory results showed that both events
      originated from Inner Mongolia and Mongolia, respectively. The increased trends
      of ROS activities during the dust storm episode in PM10 were observed for all the
      dust storms owing to a higher concentration of water-soluble components for all
      the PM10 samples compared to nondust storm ones. Interestingly, the correlations
      between DTT consumption with water-soluble species yield interesting results
      about the spatial variability of redox activity between sites. In particular, a
      tracer of soil suspension, namely Fe, contributed the most fraction to ROS
      variability in the urban background site. Water-soluble organic carbon (WSOC)
      made the highest contribution to ROS variability, suggesting that vehicle
      emission might be important driving factors of the PM-induced oxidative stress in
      the urban site. 

PMID- 24728574
TI  - Carbazole angular dioxygenation and mineralization by bacteria isolated from
      hydrocarbon-contaminated tropical African soil.
AB  - Four bacterial strains isolated from hydrocarbon-contaminated soils in Lagos,
      Nigeria, displayed extensive degradation abilities on carbazole, an N
      heterocyclic aromatic hydrocarbon. Physicochemical analyses of the sampling sites
      (ACPP, MWO, NESU) indicate gross pollution of the soils with a high hydrocarbon
      content (157,067.9 mg/kg) and presence of heavy metals. Phylogenetic analysis of
      the four strains indicated that they were identified as Achromobacter sp. strain
      SL1, Pseudomonas sp. strain SL4, Microbacterium esteraromaticum strain SL6, and
      Stenotrophomonas maltophilia strain BA. The rates of degradation of carbazole by
      the four isolates during 30 days of incubation were 0.057, 0.062, 0.036, and
      0.050 mg L(-1) h(-1) for strains SL1, SL4, SL6, and BA. Gas chromatographic (GC)
      analyses of residual carbazole after 30 days of incubation revealed that 81.3,
      85, 64.4, and 76 % of 50 mg l(-1) carbazole were degraded by strains SL1, SL4,
      SL6, and BA, respectively. GC-mass spectrometry and high-performance liquid
      chromatographic analyses of the extracts from the growing and resting cells of
      strains SL1, SL4, and SL6 cultured on carbazole showed detection of anthranilic
      acid and catechol while these metabolites were not detected in strain BA under
      the same conditions. This study has established for the first time carbazole
      angular dioxygenation and mineralization by isolates from African environment. 

PMID- 24728575
TI  - On the real performance of cation exchange resins in wastewater treatment under
      conditions of cation competition: the case of heavy metal pollution.
AB  - Sorption performance of cation-exchange resins Amberlite(r) IRN77 and AmberliteTM
      IRN9652 toward Cs(I) and Sr(II) has been tested in single-component aqueous
      solutions and simulated waste effluents containing other monovalent (Effluent 1)
      or divalent (Effluent 2) metal cations, as well as nitrate, borate, or carbonate
      anions. The individual sorption isotherms of each main component were measured by
      the solution depletion method. The differential molar enthalpy changes
      accompanying the ion-exchange between Cs+ or Sr2+ ions and protons at the resin
      surface from single-component nitrate solutions were measured by isothermal
      titration calorimetry and they showed a higher specificity of the two resins
      toward cesium. Compared to the retention limits of both resins under such
      idealized conditions, an important depression in the maximum adsorption capacity
      toward each main component was observed in multication systems. The overall
      effect of ion exchange process appeared to be an unpredictable outcome of the
      individual sorption capacities of the two resins toward various cations as a
      function of the cation charge, size, and concentration. The cesium retention
      capacity of the resins was diminished to about 25% of the "ideal" value in
      Effluent 1 and 50% in Effluent 2; a further decrease to about 15% was observed
      upon concomitant strontium addition. The uptake of strontium by the resins was
      found to be less sensitive to the addition of other metal components: the
      greatest decrease in the amount adsorbed was 60% of the ideal value in the two
      effluents for Amberlite(r) IRN77 and 75% for AmberliteTM IRN9652. It was
      therefore demonstrated that any performance tests carried out under idealized
      conditions should be exploited with much caution to predict the real performance
      of cation exchange resins under conditions of cation competition.

PMID- 24728576
TI  - Effects of realistic doses of atrazine, metolachlor, and glyphosate on lipid
      peroxidation and diet-derived antioxidants in caged honey bees (Apis mellifera).
AB  - The decline in the population of pollinators is a worrying phenomenon worldwide.
      In North America, the extensive use of herbicides in maize and soya crops may
      affect the health of nontarget organisms like the honey bee. In this study, caged
      honey bees were exposed to realistic doses of atrazine, metolachlor, and
      glyphosate for 10 days via contaminated syrup. Peroxidation of lipids was
      evaluated using the thiobarbituric acid reactive substance (TBARS) test, and diet
      derived antioxidants-carotenoids, all-trans-retinol (at-ROH) and alpha-tocopherol
      were detected and quantified using reversed-phase HPLC techniques. Significant
      increases in syrup consumption were observed in honey bees exposed to
      metolachlor, and a lower TBARS value was recorded for the highest dose. No
      relationship was observed between the peroxidation of lipids and the levels of
      antioxidants. However, beta-carotene, which was found to be the most abundant
      carotenoid, and at-ROH (derived from beta-carotene) both decreased with
      increasing doses of atrazine and glyphosate. In contrast, metolachlor increased
      levels of at-ROH without any effects on beta-carotene. These results show that
      the honey bee carotenoid-retinoid system may be altered by sublethal field
      realistic doses of herbicides. 

PMID- 24728577
TI  - Clinical and molecular characterization of the BRCA2 p.Asn3124Ile variant reveals
      substantial evidence for pathogenic significance.
AB  - Variants of uncertain clinical significance (VUS) in the high-penetrance breast
      cancer susceptibility genes BRCA1 and BRCA2 represent a major obstacle in genetic
      counseling of high-risk breast cancer families. We analyzed a missense VUS
      located in BRCA2 (p.Asn3124Ile; HGVS: BRCA2 c.9371A > T) present in seven
      independent high-risk breast cancer families that were counseled and genetically
      tested in South-West Germany. The VUS was identified by DNA sequencing. We
      analyzed co-occurrence with deleterious BRCA1/2 mutations, segregation,
      evolutionary conservation, in silico impact prediction, and prevalence in the
      general population. All carriers of the VUS suffered from breast or ovarian
      cancer. In two families, an additional high burden of other cancers such as
      pancreatic, prostate, and gastric cancers was reported, one further family
      included two cases of male breast cancer. The VUS did not co-occur with
      deleterious BRCA1/2 mutations and segregated in two affected individuals of one
      family. In contrast to the 7/1,347 (0,5 %) tested high-risk BC families without
      clearly pathogenic mutations in BRCA1/2, none of 3,126 healthy population
      controls sharing the same ethnic and geographical background were found to carry
      this VUS (p = 0.0002). In-silico prediction revealed strong evolutionary
      conservation of the asparagine residue, residing in the C-terminal
      oligonucleotide-binding-fold-3 region, and a most likely damaging impact of this
      exchange on the protein structure. The BRCA2 p.Asn3124Ile (BRCA2 c.9371A > T)
      variant is a rare mutation with a damaging effect on the BRCA2 protein that is
      strongly associated with familial breast and ovarian cancer risk, indicating its
      most likely pathogenic nature and clinical relevance. 

PMID- 24728578
TI  - Randomized phase II study of weekly paclitaxel with and without carboplatin
      followed by cyclophosphamide/epirubicin/5-fluorouracil as neoadjuvant
      chemotherapy for stage II/IIIA breast cancer without HER2 overexpression.
AB  - Addition of carboplatin to neoadjuvant chemotherapy in HER2-negative breast
      cancer may improve pathological complete response (pCR) rates. We evaluated the
      efficacy and safety of carboplatin and weekly paclitaxel (wPTX) followed by
      cyclophosphamide, epirubicin, and 5-fluorouracil (CEF) as neoadjuvant
      chemotherapy for HER2-negative breast cancer. Patients with stage II/IIIA HER2
      negative breast cancer were randomly assigned to preoperatively receive CP-CEF
      (four 3-week cycles of carboplatin [area under the curve 5 mg/mL/min, day 1] and
      wPTX [80 mg/m(2), day 1, 8, 15] followed by four 3-week cycles of CEF
      [500/100/500 mg/m(2)] or P-CEF (four cycles of wPTX followed by four cycles of
      CEF). The primary objective was pCR rate. Of 181 eligible patients, 89 were
      randomly assigned to the CP-CEF and 92 to the P-CEF. Two patients in each arm
      refused to receive neoadjuvant chemotherapy. Overall 88 patients in the CP-CEF
      and 91 patients in the P-CEF were assessable for efficacy and safety. The pCR
      rate in the CP-CEF was significantly higher than that in the P-CEF (31.8 vs. 17.6
      %, one-sided P = 0.01). Among patients with triple-negative breast cancer, the
      pCR rate in the CP-CEF was significantly higher than that in the P-CEF [61.2
      (23/37) vs. 26.3 % (10/38), P = 0.003]. Grade 3-4 neutropenia was observed in the
      CP-CEF more frequently than in the P-CEF (65.9 vs. 38.5 %). Adding carboplatin to
      neoadjuvant wPTX followed by CEF for HER2-negative breast cancer improved the pCR
      rate and exacerbated hematotoxicity. 

PMID- 24728579
TI  - Partnership for sustainability in cardiac surgery to address critical rheumatic
      heart disease in sub-Saharan Africa: the experience from Rwanda.
AB  - IMPORTANCE: Rheumatic heart disease (RHD) in the developing world results in
      critical disability among children, adolescents, and young adults-marginalizing a
      key population at its peak age of productivity. Few regions in sub-Saharan Africa
      have independently created an effective strategy to detect and treat
      streptococcal infection and mitigate its progression to RHD. OBJECTIVE: We
      describe a unique collaboration, where the Rwanda Ministry of Health, the Rwanda
      Heart Foundation, and an expatriate humanitarian cardiac surgery program have
      together leveraged an innovative partnership as a means to expand Rwanda's
      current capacity to address screening and primary prevention, as well as provide
      life-saving cardiac surgery for patients with critical RHD. EVIDENCE REVIEW:
      Interviews with key personnel and review of administrative records were conducted
      to obtain qualitative and quantitative data on the recruitment of clinical
      personnel, procurement of equipment, and program finances. The number of surgical
      cases completed and the resultant clinical outcomes are reviewed. FINDINGS: From
      2008 to 2013, six annual visits were completed. A total of 128 prosthetic valves
      have been implanted in 86 complex patients in New York Heart Association (NYHA)
      class III or IV heart failure, with excellent clinical outcomes (5 % 30-day
      mortality). Postoperative complications included a cerebrovascular accident (n =
      1) and hemorrhage, requiring reoperation (n = 2). All procedures were performed
      with participation of local personnel. CONCLUSIONS AND RELEVANCE: This strategy
      provides a reliable and consistent model of sophisticated specialty care
      delivery; inclusive of patient-centered cardiac surgery, mentorship, didactics,
      skill transfer, and investment in a sustainable cardiac program to address
      critical RHD in sub-Saharan Africa.

PMID- 24728580
TI  - Ethical issues in surgical innovation.
AB  - Innovation is responsible for most advances in the field of surgery. Innovative
      approaches to solving clinical problems have significantly decreased morbidity
      and mortality for many surgical procedures, and have led to improved patient
      outcomes. While innovation is motivated by the surgeon's expectation that the new
      approach will be beneficial to patients, not all innovations are successful or
      result in improved patient care. The ethical dilemma of surgical innovation lies
      in the uncertainty of whether a particular innovation will prove to be a "good
      thing." This uncertainty creates challenges for surgeons, patients, and the
      healthcare system. By its very nature, innovation introduces a potential risk to
      patient safety, a risk that may not be fully known, and it simultaneously fosters
      an optimism bias. These factors increase the complexity of informed consent and
      shared decision making for the surgeon and the patient. Innovative procedures and
      their associated technology raise issues of cost and resource distribution in the
      contemporary, financially conscious, healthcare environment. Surgeons and
      institutions must identify and address conflicts of interest created by the
      development and application of an innovation, always preserving the best interest
      of the patient above the academic or financial rewards of success. Potential
      strategies to address the challenges inherent in surgical innovation include
      collecting and reporting objective outcomes data, enhancing the informed consent
      process, and adhering to the principles of disclosure and professionalism. As
      surgeons, we must encourage creativity and innovation while maintaining our
      ethical awareness and responsibility to patients. 

PMID- 24728581
TI  - The importance of an ethics curriculum in surgical education.
AB  - The nature of surgical work provides fertile ground in which ethical problems can
      grow. The concept of what it means to be a "good surgeon" includes the ability to
      reason and deliberate about how the surgeon's unique technical capabilities
      integrate with larger society. Ethics education at the resident level is
      important for several reasons. It can ensure that care is delivered in a socially
      and ethically responsible manner through global and emergent effects on
      institutions and traditions. It will prepare residents for leadership positions.
      It can allow residents to confront issues, such as the scientific
      underdetermination of surgical practice, the application of new technologies to
      trusting patients that have been developed by for-profit companies, and a
      surgical environment that is becoming increasingly institutionalized. Resident
      ethics education provides the opportunity for a model of collective deliberation
      to be developed that can be used to make sense of ethical problems as they arise.

PMID- 24728582
TI  - Factors predicting post-thyroidectomy hypoparathyroidism recovery.
AB  - BACKGROUND: Hypoparathyroidism is the most common complication after
      thyroidectomy and the main reason for frequent outpatient visits; however, there
      is a poor understanding of its outcomes and no clear follow-up strategies are
      available. We aimed to predict post-thyroidectomy hypoparathyroidism outcomes and
      identify relevant factors. METHODS: A multicenter, standardized prospective study
      was conducted. The parathyroid hormone level (PTH) was measured preoperatively
      and at the first hour after surgery, then at each outpatient follow-up visit
      after 1 week, 3 weeks, and 1 month, and then every 2 months, until it either
      reached normal values or up to 6 months. Cox proportional hazard modeling was
      used to determine the factors that affect PTH recovery. A Weibull distribution
      model was used to predict time to recovery. Both models were evaluated by
      goodness of fit. RESULTS: A total of 186 patients were enrolled in the study; 53
      (28.5 %) developed hypoparathyroidism, 47 of them (88.6 %) females. Their mean
      age was 41.2 years, and 11.4 % were diabetic. Of these women, 33 (62.3 %)
      recovered within 1 month, 10 (18.9 %) recovered after 1 month but within 6
      months, 7 (13.2 %) did not recover within 6 months, and 3 (5.6 %) missed follow
      up. Factors that are found to affect and predict the speed of recovery were the
      preoperative PTH level, perioperative percent drop in PTH level, diabetes
      mellitus, and gender. CONCLUSIONS: This study provides potentially useful
      information for early prediction of PTH recovery, and it highlights the factors
      that affect the course of hypoparathyroidism recovery, which in turn should be
      reflected in better patient management, improved patient satisfaction, and
      overall cost-effectiveness.

PMID- 24728584
TI  - The impact of radiotherapy on quality of life for cancer patients: a longitudinal
      study.
AB  - PURPOSE: The aim of this study was to assess for changes in quality of life (QOL)
      among cancer patients who undergo radiotherapy (RT) and to identify factors that
      influence QOL in this group. MATERIALS AND METHODS: Three hundred sixty-seven
      cancer patients who received curative RT were investigated using the EORTC QLQ
      C30 questionnaire at the start of RT, end of RT, and 1 and 6 months post-RT.
      RESULTS: The patients were 49 % women, 51 % men, and median age at diagnosis was
      57 years (range, 16-86 years). Compared to pre-RT, at the end of RT, the global
      health status score (p < 0.001), nausea/vomiting (p < 0.001), and apetite loss
      scores (p < 0.001) were significantly poorer. Compared to the end of RT, at 1 and
      6 months post-RT, global health status, all functional, and all symptom scores
      were significantly improved (p < 0.001). Patient sex influenced scores for pain
      (p = 0.036), appetite loss (p = 0.027), and financial difficulty (p = 0.003).
      Performance status influenced scores for global health status (p = 0.006),
      physical functioning (p < 0.001), cognitive functioning (p = 0.001), and role
      functioning (p = 0.021). Comorbidity influenced fatigue score (p < 0.001). Cancer
      stage influenced scores for physical functioning (p = 0.001), role functioning (p
      = 0.010), and fatigue (p < 0.001). Treatment modality (chemoRT vs. RT alone)
      influenced scores for physical functioning (p = 0.016), fatigue (p < 0.001),
      nausea/vomiting (p = 0.009), and appetite loss (p < 0.001); and RT field
      influenced scores for nausea/vomiting (p = 0.001), appetite loss (p = 0.003), and
      diarrhea (p = 0.037). Radiotherapy dose functioning (p < 0.001), cognitive
      functioning (p < 0.001), social functioning (p < 0.001), fatigue (p < 0.001), and
      pain (<60 vs >=60 Gy) had an effect on scores for physical functioning (p <
      0.001), role functioning (p < 0.001), emotional (p < 0.001), insomnia (p <
      0.001), constipation (p < 0.001). CONCLUSION: While RT negatively affects cancer
      patients' QOL, restoration tends to be rapid and patients report significant
      improvement by 1 month post-RT. Various patient- and disease-specific factors and
      RT modality affect QOL in this patient group. We advocate measuring cancer
      patients' QOL regularly as part of routine patient management.

PMID- 24728585
TI  - Mandatory communication skills training for oncologists: enforcement does not
      substantially impact satisfaction.
AB  - PURPOSE: Even though there is evidence that both patients and oncology clinicians
      are affected by the quality of communication and that communication skills can be
      effectively trained, so-called Communication Skills Trainings (CSTs) remain
      heterogeneously implemented. METHODS: A systematic evaluation of the level of
      satisfaction of oncologists with the Swiss CST before (2000-2005) and after (2006
      2012) it became mandatory. RESULTS: Levels of satisfaction with the CST were
      high, and satisfaction of physicians participating on a voluntary or mandatory
      basis did not significantly differ for the majority of the items. CONCLUSIONS:
      The evaluation of physicians' satisfaction over the years and after introduction
      of mandatory training supports recommendations for generalized implementation of
      CST and mandatory training for medical oncologists.

PMID- 24728583
TI  - Regulating the large Sec7 ARF guanine nucleotide exchange factors: the when,
      where and how of activation.
AB  - Eukaryotic cells require selective sorting and transport of cargo between
      intracellular compartments. This is accomplished at least in part by vesicles
      that bud from a donor compartment, sequestering a subset of resident protein
      "cargos" destined for transport to an acceptor compartment. A key step in vesicle
      formation and targeting is the recruitment of specific proteins that form a coat
      on the outside of the vesicle in a process requiring the activation of regulatory
      GTPases of the ARF family. Like all such GTPases, ARFs cycle between inactive,
      GDP-bound, and membrane-associated active, GTP-bound, conformations. And like
      most regulatory GTPases the activating step is slow and thought to be rate
      limiting in cells, requiring the use of ARF guanine nucleotide exchange factor
      (GEFs). ARF GEFs are characterized by the presence of a conserved, catalytic Sec7
      domain, though they also contain motifs or additional domains that confer
      specificity to localization and regulation of activity. These domains have been
      used to define and classify five different sub-families of ARF GEFs. One of
      these, the BIG/GBF1 family, includes three proteins that are each key regulators
      of the secretory pathway. GEF activity initiates the coating of nascent vesicles
      via the localized generation of activated ARFs and thus these GEFs are the
      upstream regulators that define the site and timing of vesicle production.
      Paradoxically, while we have detailed molecular knowledge of how GEFs activate
      ARFs, we know very little about how GEFs are recruited and/or activated at the
      right time and place to initiate transport. This review summarizes the current
      knowledge of GEF regulation and explores the still uncertain mechanisms that
      position GEFs at "budding ready" membrane sites to generate highly localized
      activated ARFs. 

PMID- 24728587
TI  - A strong and tough interpenetrating network hydrogel with ultrahigh compression
      resistance.
AB  - A novel interpenetrating network (IPN) hydrogel with ultrahigh compressive
      strength and fracture strain has been prepared using the copolymer of 2
      acrylamide-2-methylpropane sulfonic acid (AMPS) and acrylamide (AM) [P(AMPS-co
      AM)] or N-isopropylacrylamide (NIPAM) [P(AMPS-co-NIPAM)] as the primary network
      and polyacrylamide (PAM) as the secondary network. The as-prepared IPN hydrogel
      of P(AMPS-co-AM)/PAM has a significantly high compressive strength (91.8 MPa),
      which is 4 times greater than that of the common PAMPS/PAM IPN hydrogel as well
      as the compressively strongest hydrogel reported in the literature. The P(AMPS-co
      AM)/PAM IPN hydrogel is tough enough not to fracture even when the compressive
      strain reaches 98%. Synchrotron radiation small-angle X-ray scattering (SAXS)
      analysis has indicated that the presence of an AM comonomer changes the size of
      the physically cross-linked domains in the IPN hydrogel, which may partially
      account for its unique mechanical properties. This study has presented the
      compressively strongest hydrogel reported to date and also provided a novel and
      feasible method to prepare the highly strong and tough hydrogel. 

PMID- 24728586
TI  - Living with cancer-related uncertainty: associations with fatigue, insomnia, and
      affect in younger breast cancer survivors.
AB  - PURPOSE: Uncertainty in cancer patients and survivors about cancer-related
      symptoms, treatment, and disease course has been related to poorer mental and
      physical health. However, little is known about whether cancer-related
      uncertainty relates with specific disease and treatment-related outcomes such as
      fatigue, insomnia, and affect disruptions. In this paper, we report these
      associations in younger survivors aged 50 years or less, a population increasing
      in prevalence. METHODS: Participants included 313 breast cancer survivors (117
      African-Americans and 196 Caucasians) who were aged 24 to 50 years and were 2 to
      4 years posttreatment. Self-reported cancer-related uncertainty (Mishel
      Uncertainty in Illness Scale-Survivor Version), fatigue (Piper Fatigue Scale
      Revised), insomnia (Insomnia Severity Index), and negative and positive affect
      (Positive and Negative Affect Schedule (PANAS)) measures were collected upon
      study entry. RESULTS: Hierarchical regression analyses controlled for relevant
      sociodemographic variables include the following: race, age, years of education,
      number of children, employment status, marital status, monthly income, smoking
      status, family history of cancer, endorsement of treatment-induced menopause, and
      religiosity. Over and above these factors, higher cancer-related uncertainty was
      significantly associated with more self-reported fatigue (beta = .43), insomnia
      (beta = .34), negative affect (beta = .43), as well as less positive affect (beta
      = -.33), all ps < .01. CONCLUSIONS: Younger breast cancer survivors who are 2-4
      years posttreatment experience cancer-related uncertainty, with higher levels
      associated with more self-reported psychophysiological disruptions. Cancer
      survivors who present in clinical settings with high uncertainty about recurrence
      or management of long-term effects of treatment may thus benefit from assessment
      of fatigue, insomnia, and affect.

PMID- 24728588
TI  - Bridging the gaps in systems biology.
AB  - Systems biology aims at creating mathematical models, i.e., computational
      reconstructions of biological systems and processes that will result in a new
      level of understanding-the elucidation of the basic and presumably conserved
      "design" and "engineering" principles of biomolecular systems. Thus, systems
      biology will move biology from a phenomenological to a predictive science.
      Mathematical modeling of biological networks and processes has already greatly
      improved our understanding of many cellular processes. However, given the massive
      amount of qualitative and quantitative data currently produced and number of
      burning questions in health care and biotechnology needed to be solved is still
      in its early phases. The field requires novel approaches for abstraction, for
      modeling bioprocesses that follow different biochemical and biophysical rules,
      and for combining different modules into larger models that still allow realistic
      simulation with the computational power available today. We have identified and
      discussed currently most prominent problems in systems biology: (1) how to bridge
      different scales of modeling abstraction, (2) how to bridge the gap between
      topological and mechanistic modeling, and (3) how to bridge the wet and dry
      laboratory gap. The future success of systems biology largely depends on bridging
      the recognized gaps. 

PMID- 24728590
TI  - UV-visible absorbance spectroscopy as a proxy for peatland dissolved organic
      carbon (DOC) quantity and quality: considerations on wavelength and absorbance
      degradation.
AB  - Absorbance in the UV or visible spectrum (UV-vis) is commonly used as a proxy for
      DOC concentrations in waters draining upland catchments. To determine the
      appropriateness of different UV-vis measurements we used surface and pore water
      samples from two Welsh peatlands in four different experiments: (i) an assessment
      of single wavelength proxies (1 nm increments between 230-800 nm) for DOC
      concentration demonstrated that 254 nm was more accurate than 400 nm. The highest
      R(2) values between absorbance and DOC concentration were generated using 263 nm
      for one sample set (R(2) = 0.91), and 230 nm for the other three sample sets
      (respective R(2) values of 0.86, 0.81, and 0.93). (ii) A comparison of different
      DOC concentration proxies, including single wavelength proxies, a two wavelength
      model, a proxy using phenolic concentration, and a proxy using the area under a
      UV spectrum at 250-350 nm. It was found that both a single wavelength proxy
      (<=263 nm) and a two wavelength model performed well for both pore water and
      surface water. (iii) An evaluation of the E2 : E3, E2 : E4, E4 : E6 ratios, and
      SUVA (absorbance at 254 nm normalised to DOC concentration) as indicators of DOC
      quality showed that the E4 : E6 ratio was subject to extensive variation over
      time, and was highly correlated between surface water and pore water, suggesting
      that it is a useful metric to determine temporal changes in DOC quality. (iv) A
      repeated weekly analysis over twelve weeks showed no consistent change in UV-vis
      absorbance, and therefore an inferred lack of degradation of total DOC in samples
      that were filtered and stored in the dark at 4  degrees C. 

PMID- 24728589
TI  - Semiconducting polymer dots with monofunctional groups.
AB  - This communication describes an approach for preparing monovalent semiconducting
      polymer dots (mPdots) with a size of 5 nm where each mPdot was composed of
      precisely a single active functional group. 

PMID- 24728591
TI  - The organization of the sphingosine 1-phosphate signaling system.
AB  - The understanding of the role of the sphingosine 1-phosphate signaling system in
      immunology and host defense has deepened exponentially over the past 12 years
      since the discovery that lymphocyte egress was reversibly modulated by
      sphingosine 1-phosphate receptors, and with the development of fingolimod, a
      prodrug of a nonselective S1P receptor agonist, for therapeutic use in the
      treatment of relapsing, remitting multiple sclerosis. Innovative genetic and
      chemical approaches, together with structural biology, now provide a more
      detailed molecular understanding of a regulated lysophospholipid ligand with a
      variety of autocrine, paracrine, and systemic effects in physiology and
      pathology, based upon selective interactions with a high affinity and selective
      evolutionary cluster of G-protein-coupled receptors.

PMID- 24728592
TI  - Structural biology of the S1P1 receptor.
AB  - The sphingosine 1 phosphate receptor family has been studied widely since the
      initial discovery of its first member, endothelium differentiation gene 1. Since
      this initial discovery, the family has been renamed and the primary member of the
      family, the S1P1 receptor, has been targeted for a variety of disease indications
      and successfully drugged for the treatment of patients with relapsing multiple
      sclerosis. Recently, the three-dimensional structure of the S1P1 receptor has
      been determined by X-ray crystallography and the specifics of the sphingosine 1
      phosphate ligand binding pocket mapped. Key structural features for the S1P1
      receptor will be reviewed and the potential binding modes of additional
      pharmacologically active agents against the receptor will be analyzed in an
      effort to better understand the structural basis of important receptor-ligand
      interactions. 

PMID- 24728593
TI  - Chemical and genetic tools to explore S1P biology.
AB  - The zwitterionic lysophospholipid Sphingosine 1-Phosphate (S1P) is a pleiotropic
      mediator of physiology and pathology. The synthesis, transport, and degradation
      of S1P are tightly regulated to ensure that S1P is present in the proper
      concentrations in the proper location. The binding of S1P to five G protein
      coupled S1P receptors regulates many physiological systems, particularly the
      immune and vascular systems. Our understanding of the functions of S1P has been
      aided by the tractability of the system to both chemical and genetic
      manipulation. Chemical modulators have been generated to affect most of the known
      components of S1P biology, including agonists of S1P receptors and inhibitors of
      enzymes regulating S1P production and degradation. Genetic knockouts and
      manipulations have been similarly engineered to disrupt the functions of
      individual S1P receptors or enzymes involved in S1P metabolism. This chapter will
      focus on the development and utilization of these chemical and genetic tools to
      explore the complex biology surrounding S1P and its receptors, with particular
      attention paid to the in vivo findings that these tools have allowed for. 

PMID- 24728595
TI  - Blood, sphingosine-1-phosphate and lymphocyte migration dynamics in the spleen.
AB  - The spleen, the largest secondary lymphoid organ, has long been known to play
      important roles in immunity against blood-borne invaders. Yet how cells migrate
      within the spleen to ensure fast and effective responses is only now coming to
      light. Chemokines and oxysterols guide lymphocytes from sites of release at
      terminal arterioles into the lymphocyte-rich white pulp. Sphingosine-1-phosphate
      (S1P) and S1P-receptor-1 (S1PR1) promote lymphocyte egress from white to red pulp
      and back to circulation. Intravital two-photon microscopy has shown that marginal
      zone (MZ) B cells that are enriched between white and red pulps undergo continual
      oscillatory migration between the MZ and follicles, ferrying antigens. Cycles of
      G-protein-coupled receptor kinase-2 (GRK2) mediated S1PR1 desensitization and
      resensitization underlie this remarkable behavior. The findings discussed in this
      review have implications for understanding how splenic antibody and T-cell
      responses are mounted, how the immunosuppressant drug FTY720 (fingolimod) affects
      the spleen, and how cell shuttling behaviors contribute to immunity. 

PMID- 24728594
TI  - S1P control of endothelial integrity.
AB  - Sphingosine 1-phosphate (S1P), a lipid mediator produced by sphingolipid
      metabolism, promotes endothelial cell spreading, vascular
      maturation/stabilization, and barrier function. S1P is present at high
      concentrations in the circulatory system, whereas in tissues its levels are low.
      This so-called vascular S1P gradient is essential for S1P to regulate much
      physiological and pathophysiological progress such as the modulation of vascular
      permeability. Cellular sources of S1P in blood has only recently begun to be
      identified. In this review, we summarize the current understanding of S1P in
      regulating vascular integrity. In particular, we discuss the recent discovery of
      the endothelium-protective functions of HDL-bound S1P which is chaperoned by
      apolipoprotein M. 

PMID- 24728596
TI  - Cytokine storm plays a direct role in the morbidity and mortality from influenza
      virus infection and is chemically treatable with a single sphingosine-1-phosphate
      agonist molecule.
AB  - Cytokine storm defines a dysregulation of and an excessively exaggerated immune
      response most often accompanying selected viral infections and several autoimmune
      diseases. Newly emerging and re-emerging infections of the respiratory tract,
      especially influenza, SARS, and hantavirus post considerable medical problems.
      Their morbidities and mortalities are often a direct result of cytokine storm.
      This chapter visits primarily influenza virus infection and resultant cytokine
      storm. It provides the compelling evidence that illuminates cytokine storm in
      influenza pathogenesis and the clear findings that cytokine storm is chemically
      tractable by therapy directed toward sphingosine-1-phosphate receptor (S1PR)
      modulation, specifically S1P1R agonist therapy. The mechanism(s) of how S1P1R
      signaling works and the pathways involved are subjects of this review. 

PMID- 24728597
TI  - Sphingosine-1 phosphate and central nervous system.
AB  - The development of fingolimod, an unselective functional antagonist of the
      interactions between sphingosine 1 phosphate (S1P) and sphingosine 1 phosphate
      receptors (S1PRs), as the first oral therapy for multiple sclerosis (MS) has been
      a milestone. The parallel intensive research on the role of S1P, sphingosine
      kinases, and the five known S1PRs, their tissue distribution and expression in
      physiological and pathological conditions have led to a wide range of interesting
      findings. The initial focus of this research in the context of developing
      fingolimod as a treatment of MS has been on its immunological effects. The wide
      distribution and important roles of sphingosine, its metabolites, and their
      receptors in the central nervous system (CNS) in general, in myelin, and in all
      cell types of this organ have spurred interest to examine S1P and its five
      receptors in the brain as well. The present review will concentrate on the latter
      area and give a brief overview of what is known about S1P/S1PR interactions in
      the CNS in physiological and pathological conditions. 

PMID- 24728598
TI  - RORs in autoimmune disease.
AB  - The retinoic acid receptor-related orphan receptor (ROR) subfamily of nuclear
      receptors are transcription factors involved in the maintenance of circadian
      rhythm and are essential for proper immune function. The T cell-specific isoform,
      RORgammat, is required for T helper 17 cells (TH17) development and it has been
      implicated in the pathogenesis of autoimmune diseases including multiple
      sclerosis and rheumatoid arthritis. Thus, pharmacological repression of RORgammat
      may provide a strategy for therapeutic intervention in autoimmune disorders. This
      chapter provides a summary of the current status for target validation and
      development of new chemical entities targeting RORgammat. 

PMID- 24728599
TI  - Genomic analysis of cyclic-di-GMP-related genes in rhizobial type strains and
      functional analysis in Rhizobium etli.
AB  - Rhizobia are soil bacteria that can fix nitrogen in symbiosis with leguminous
      plants or exist free living in the rhizosphere. Crucial to their complex
      lifestyle is the ability to sense and respond to diverse environmental stimuli,
      requiring elaborate signaling pathways. In the majority of bacteria, the
      nucleotide-based second messenger cyclic diguanosine monophosphate (c-di-GMP) is
      involved in signal transduction. Surprisingly, little is known about the
      importance of c-di-GMP signaling in rhizobia. We have analyzed the genome
      sequences of six well-studied type species (Bradyrhizobium japonicum,
      Mesorhizobium loti, Rhizobium etli, Rhizobium leguminosarum, Sinorhizobium
      fredii, and Sinorhizobium meliloti) for proteins possibly involved in c-di-GMP
      signaling based on the presence of four domains: GGDEF (diguanylate cyclase), EAL
      and HD-GYP (phosphodiesterase), and PilZ (c-di-GMP sensor). We find that rhizobia
      possess a high number of these proteins. Conservation analysis suggests that c-di
      GMP signaling proteins modulate species-specific pathways rather than ancient
      rhizobia-specific processes. Two hybrid GGDEF-EAL proteins were selected for
      functional analysis, R. etli RHE_PD00105 (CdgA) and RHE_PD00137 (CdgB).
      Expression of cdgA and cdgB is repressed by the alarmone (p)ppGpp. cdgB is
      significantly expressed on plant roots and free living. Mutation of cdgA, cdgB,
      or both does not affect plant root colonization, nitrogen fixation capacity,
      biofilm formation, motility, and exopolysaccharide production. However,
      heterologous expression of the individual GGDEF and EAL domains of each protein
      in Escherichia coli strongly suggests that CdgA and CdgB are bifunctional
      proteins, possessing both diguanylate cyclase and phosphodiesterase activities.
      Taken together, our results provide a platform for future studies of c-di-GMP
      signaling in rhizobia.

PMID- 24728600
TI  - Expression and purification of cyto-insectotoxin (Cit1a) using silkworm larvae
      targeting for an antimicrobial therapeutic agent.
AB  - Antimicrobial peptides (AMPs), both synthetic and from natural sources, have
      raised interest recently as potential alternatives to antibiotics. Cyto
      insectotoxin (Cit1a) is a 69-amino-acid antimicrobial peptide isolated from the
      venom of the central Asian spider Lachesana tarabaevi. The synthetic gene Cit1a
      fused with the enhanced green fluorescent protein (EGFP) gene was expressed as
      the EGFP-Cit1a fusion protein using a cysteine protease-deleted Bombyx mori
      nucleopolyhedrovirus (BmNPV-CP(-)) bacmid in silkworm larva and pupa. The
      antimicrobial effect of the purified protein was assayed using disk diffusion and
      broth microdilution methods. The minimum inhibitory concentration of EGFP-Cit1a
      was also measured against several bacterial strains and showed similar
      antimicrobial activity to that of the synthetic Cit1a reported earlier. The EGFP
      Cit1a fusion protein showed antibiotic activity toward gram-positive and gram
      negative bacteria at the micromolar concentration level. These results show that
      active Cit1a can be produced and purified in silkworm, although this peptide is
      insecticidal. This study demonstrates the potential of active Cit1a purified from
      silkworms to use as an antimicrobial agent. 

PMID- 24728601
TI  - [Pharmacogenic osteoporosis beyond cortisone. Proton pump inhibitors, glitazones
      and diuretics].
AB  - BACKGROUND: [corrected] There are many drugs which can cause osteoporosis or at
      least favor its initiation. The effect of hormones and drugs with antihormonal
      activity, such as glucocorticoids and aromatase inhibitors, on initiation of
      osteoporosis is well known. In addition, proton pump inhibitors, glitazones and
      diuretics also influence the formation of osteoporosis. MATERIAL AND METHODS: The
      results of currently available studies on the correlation between proton pump
      inhibitors, glitazones and diuretics on formation of osteoporosis were evaluated
      and summarized. RESULTS: Proton pump inhibitors and glitazones increase the risk
      for osteoporotic fractures. Loop diuretics may slightly increase fracture risk,
      whereas thiazides were shown to be osteoprotective by reducing fracture
      probability on a relevant scale. CONCLUSION: Proton pump inhibitors should not be
      prescribed without serious consideration and then only as long as necessary.
      Alternatively, the administration of the less effective H2 antagonists should be
      considered when possible due to the reduction of acid secretion. Because the long
      term intake of thiazides is associated with a clinically relevant reduction in
      the risk of fractures and they are economic and well-tolerated, prescription can
      be thoroughly recommended within the framework of differential diagnostic
      considerations in an appropriate clinical context. The briefly increased risk of
      falling immediately after starting diuretic therapy is the only point which needs
      to be considered.

PMID- 24728602
TI  - Sensorimotor gating is disrupted by acute but not chronic systemic exposure to
      caffeine in mice.
AB  - RATIONALE: Caffeine is a psychostimulant drug that blocks adenosine A1 and A2A
      receptors (A1Rs and A2ARs). However, its ability to disrupt early sensory gating
      as indexed by prepulse inhibition (PPI), which is consistently disrupted by other
      psychostimulant agents, has never been convincingly demonstrated. OBJECTIVES: To
      compare the impact of caffeine on PPI expression in C57BL/6 mice by two dose
      response experiments differing in terms of chronicity, regimen, and route of
      administration. To study separately the acute effect of selective antagonists
      against A1R or A2AR. METHODS: Caffeine (10, 30, 100 mg/kg, intraperitoneal
      (i.p.)) was either administered shortly before testing or via caffeinated
      drinking water (0.3, 1.0, 2 g/l) in home cages over 3 weeks. Two separate dose
      response studies tested the acute effect of the selective A1R antagonist, 1,3
      dipropyl-8 cyclopentyl xanthine (DPCPX), and the selective A2AR antagonist, 5
      amino-7-(2-phenylethyl)-2-(2-furyl)-pyrazolo-[4,3-e]-1,2,4-triazolo[1,5-c] (SCH
      58261) (0.2, 1.0, 5.0 mg/kg, i.p.). The two drugs were combined in a final
      experiment to identify their potential synergistic interaction. RESULTS: While
      the two lower acute doses of caffeine attenuated PPI, the highest dose
      potentiated PPI. By contrast, chronic caffeine exposure did not affect PPI.
      Neither DPCPX nor SCH 58261 altered PPI, and no synergism was observed when the
      two drugs were combined. CONCLUSIONS: This is the first demonstration that acute
      caffeine disrupts PPI, but the relative contribution of A1R and A2AR blockade
      remains unclear, and possible non-adenosinergic mechanisms cannot be ruled out.
      The null effect under chronic caffeine exposure might involve the development of
      tolerance, but the precise receptor subtypes involved also warrant further
      investigation.

PMID- 24728603
TI  - MDMA alters emotional processing and facilitates positive social interaction.
AB  - BACKGROUND: +/-3,4-Methylenedioxymethamphetamine (MDMA, "ecstasy") produces
      "prosocial" effects, such as feelings of empathy and closeness, thought to be
      important to its abuse and its value in psychotherapy. However, it is not fully
      understood how MDMA alters basic emotional processes to produce these effects, or
      whether it produces corresponding changes in actual social behavior. Here, we
      examined how MDMA affects perceptions of and responses to emotional expressions,
      and tested its effects on behavior during a social interaction. We also examined
      whether MDMA's prosocial effects related to a measure of abuse liability.
      METHODS: Over three sessions, 36 healthy volunteers with previous ecstasy use
      received MDMA (0.75, 1.5 mg/kg) and placebo under double-blind conditions. We
      measured (i) mood and cardiovascular effects, (ii) perception of and
      psychophysiological responses to emotional expressions, (iii) use of positive and
      negative words in a social interaction, and (iv) perceptions of an interaction
      partner. We then tested whether these effects predicted desire to take the drug
      again. RESULTS: MDMA slowed perception of angry expressions, increased
      psychophysiological responses to happy expressions, and increased positive word
      use and perceptions of partner empathy and regard in a social interaction. These
      effects were not strongly related to desire to take the drug again. CONCLUSIONS:
      MDMA alters basic emotional processes by slowing identification of negative
      emotions and increasing responses to positive emotions in others. Further, it
      positively affects behavior and perceptions during actual social interaction.
      These effects may contribute to the efficacy of MDMA in psychotherapy, but appear
      less closely related to its abuse potential.

PMID- 24728604
TI  - Transoral parathyroid surgery--a new alternative or nonsense?
AB  - PURPOSE: In recent years, several endoscopic techniques have been explored in
      thyroid and parathyroid surgery, but only few gained acceptance among patients
      and surgeons. Based on extensive human cadaver and animal studies, we developed a
      technique for transoral partial parathyroidectomy (TOPP), which was performed for
      the first time in a patient with primary hyperparathyroidism (pHPT). We now
      report on results and the acceptance of this new technique 2 years after its
      implementation. METHODS: A pilot study was initiated to recruit a total of 10
      patients with benign sporadic pHPT and a preoperatively localized parathyroid
      adenoma eligible for initial parathyroidectomy. The study protocol was approved
      by the ethics committee, and an insurance for unforeseen complications and risks
      was procured. Data of all patients evaluated and operated were prospectively
      collected, and follow-up examinations were carried out for 19 months on average,
      which included clinical examinations; ultrasonography; Ear, Nose, and Throat
      (ENT) investigations; and blood testing. RESULTS: Between January 2010 and May
      2012, 75 patients with pHPT and a preoperative localized parathyroid adenoma were
      eligible for TOPP. After detailed information about the transoral procedure, only
      five (7 %) female patients consent to undergo TOPP. In three patients, a
      parathyroid adenoma could be removed via the transoral access, In two patients,
      the procedure had to be converted to the conventional technique. Median time
      until resection of a parathyroid adenoma was 122 min (range, 45-175). One patient
      had a transient recurrent laryngeal nerve palsy, while one patient suffered from
      a transient palsy of the right hypoglossal nerve and a slight but persisting
      dysgeusia. Three patients developed a hematoma of the mouth floor and swallowing
      problems. In four patients, the visual analog scale (VAS) pain score was high
      (>7) within the first 2 postoperative days. CONCLUSIONS: Although TOPP is
      feasible, it is poorly accepted by patients and its complication rate is high.
      Thus, TOPP is nonsense with currently available devices.

PMID- 24728605
TI  - Provider status and the need for additional qualified residency opportunities-
      response to Kudla.

PMID- 24728606
TI  - Influence of the base and diluent monomer on network characteristics and
      mechanical properties of neat resin and composite materials.
AB  - This study evaluated the effect of the combination of two dimethacrylate-based
      monomers [bisphenol A diglycidyl dimethacrylate (BisGMA) or bisphenol A
      ethoxylated dimethacrylate (BisEMA)] with diluents either derived from ethylene
      glycol dimethacrylate (ethylene glycol dimethacrylate, diethylene glycol
      dimethacrylate, triethylene glycol dimethacrylate, tetraethylene glycol
      dimethacrylate) or 1,10-decanediol dimethacrylate (D3MA) on network
      characteristics and mechanical properties of neat resin and composite materials.
      The degree of conversion, maximum rate of polymerization and water
      sorption/solubility of unfilled resins and the flexural strength and
      microhardness of composites (after 24 h storage in water and 3 months storage in
      a 75 vol% ethanol aqueous solution) were evaluated. Data were analyzed with two
      way ANOVA and Tukey's test (alpha = 0.05). The higher conversion and lower water
      sorption presented by BisEMA co-polymers resulted in greater resistance to
      degradation in ethanol compared with BisGMA-based materials. In general,
      conversion and mechanical properties were optimized with the use of long-chain
      dimethacrylate derivatives of ethylene glycol. D3MA rendered more hydrophobic
      materials, but with relatively low conversion and mechanical properties.

PMID- 24728607
TI  - Genetic variants in loci 1p13 and 9p21 and fatal coronary heart disease in a
      Norwegian case-cohort study.
AB  - Single nucleotide polymorphisms (SNPs) in loci 1p13 and 9p21 have previously been
      found to be associated with incident coronary heart disease (CHD). This study
      aimed to investigate whether these SNPs show associations with fatal CHD in a
      population-based cohort study after adjustment for socioeconomic- and lifestyle
      related CHD risk factors not commonly included in genetic association studies.
      Using the population-based Cohort of Norway (CONOR), a nested case-cohort study
      was set up and DNA from 2,953 subjects (829 cases and 2,124 non-cases) were
      genotyped. The association with fatal CHD was estimated for four SNPs, three from
      locus 1p13 and one from locus 9p21. Multivariable Cox regression was used to
      estimate unstratified and gender-stratified hazard ratios while adjusting for
      major CHD risk factors. The associations between three SNPs from locus 1p13 and
      non-HDL cholesterol levels were also estimated. Men homozygous for the risk
      alleles on rs1333049 (9p21) and rs14000 (1p13) were found to have significantly
      increased hazard ratios in crude and adjusted models, and the hazard ratios
      remained statistically significant when both genders were analyzed together.
      Adjustment for additional socioeconomic- and lifestyle-related CHD risk factors
      influenced the association estimates only slightly. No significant associations
      were observed between the other two SNPs in loci 1p13 (rs599839 and rs646776) and
      CHD mortality in either gender. Both rs599839 and rs646776 showed significant,
      gradual increases in non-HDL cholesterol levels with increasing number of risk
      alleles. This study confirms the association between 9p21 (rs1333049) and fatal
      CHD in a Norwegian population-based cohort. The effect was not influenced by
      several socioeconomic- and lifestyle-related risk factors. Our results show that
      1p13 (rs14000) may also be associated with fatal CHD. SNPs at 1p13 (rs599839 and
      rs646776) were associated with non-HDL cholesterol levels. 

PMID- 24728608
TI  - Microarray analysis of differentially expressed genes engaged in fruit
      development between table and wine grape.
AB  - Microarray analysis of genes can provide individual gene-expression profiles and
      new insights for elucidating biological mechanisms responsible for fruit
      development. To obtain an overall view on expression profiles of metabolism
      related genes involved in fruit development of table and wine grapes, a
      microarray system comprising 15,403 ESTs was used to compare the expressed genes.
      The expression patterns from the microarray analysis were validated with
      quantitative real-time polymerase chain reaction analysis of 18 selected genes of
      interest. During the entire fruit development stage, 2,493 genes exhibited at
      least 2.0-fold differences in expression levels with 1,244 genes being up
      regulated and 1,249 being down-regulated. Following gene ontology analysis, only
      929 differentially expressed (including 403 up-regulated and 526 down-regulated)
      genes were annotated in table and wine grapes. These differentially expressed
      genes were found to be mainly involved in carbohydrate metabolism, biosynthesis
      of secondary metabolites as well as energy, lipid and amino acid metabolism via
      KEGG. Our results provide new insights into the molecular mechanisms and
      expression profiles of genes in the fruit development stage of table and wine
      grapes. 

PMID- 24728609
TI  - Nutrient restriction induces failure of reproductive function and molecular
      changes in hypothalamus-pituitary-gonadal axis in postpubertal gilts.
AB  - People on a diet to lose weight may be at risk of reproductive failure. To
      investigate the effects of nutrient restriction on reproductive function and the
      underlying mechanism, changes of reproductive traits, hormone secretions and gene
      expressions in hypothalamus-pituitary-gonadal axis were examined in postpubertal
      gilts at anestrus induced by nutrient restriction. Gilts having experienced two
      estrus cycles were fed a normal (CON, 2.86 kg/d) or nutrient restricted (NR, 1
      kg/d) food regimens to expect anestrus. NR gilts experienced another three estrus
      cycles, but did not express estrus symptoms at the anticipated fourth estrus.
      Blood samples were collected at 5 days' interval for consecutive three times for
      measurement of hormone concentrations at the 23th day of the fourth estrus cycle.
      Individual progesterone concentrations of NR gilts from three consecutive blood
      samples were below 1.0 ng/mL versus 2.0 ng/mL in CON gilts, which was considered
      anestrus. NR gilts had impaired development of reproductive tract characterized
      by absence of large follicles (diameter >= 6 mm), decreased number of corepus
      lutea and atrophy of uterus and ovary tissues. Circulating concentrations of IGF
      I, kisspeptin, estradiol, progesterone and leptin were significantly lower in NR
      gilts than that in CON gilts. Nutrient restriction down-regulated gene
      expressions of kiss-1, G-protein coupled protein 54, gonadotropin-releasing
      hormone, estrogen receptor alpha, progesterone receptor, leptin receptor,
      follicle-stimulating hormone and luteinizing hormone and insulin-like growth
      factor I in hypothalamus-pituitary-gonadal axis of gilts. Collectively, nutrient
      restriction resulted in impairment of reproductive function and changes of
      hormone secretions and gene expressions in hypothalamus-pituitary-gonadal axis,
      which shed light on the underlying mechanism by which nutrient restriction
      influenced reproductive function.

PMID- 24728611
TI  - Is it ethical for journals to request self-citation?
AB  - By following the recently published paper in Science titled "Coercive Citation in
      Academic Publishing", in this paper, we aim to discuss the demand of some
      journals that request authors to cite recently published papers in that journal
      to increase the impact factor of that journal. It will be mentioned that some of
      these demands are not ethical and consequently will diminish the reputation of
      the journal. 

PMID- 24728610
TI  - Staphylococcus aureus mobile genetic elements.
AB  - Among the bacteria groups, most of them are known to be beneficial to human being
      whereas only a minority is being recognized as harmful. The pathogenicity of
      bacteria is due, in part, to their rapid adaptation in the presence of selective
      pressures exerted by the human host. In addition, through their genomes, bacteria
      are subject to mutations, various rearrangements or horizontal gene transfer
      among and/or within bacterial species. Bacteria's essential metabolic functions
      are generally encoding by the core genes. Apart of the core genes, there are
      several number of mobile genetic elements (MGE) acquired by horizontal gene
      transfer that might be beneficial under certain environmental conditions. These
      MGE namely bacteriophages, transposons, plasmids, and pathogenicity islands
      represent about 15% Staphylococcus aureus genomes. The acquisition of most of the
      MGE is made by horizontal genomic islands (GEI), recognized as discrete DNA
      segments between closely related strains, transfer. The GEI contributes to the
      wide spread of microorganisms with an important effect on their genome plasticity
      and evolution. The GEI are also involve in the antibiotics resistance and
      virulence genes dissemination. In this review, we summarize the mobile genetic
      elements of S. aureus.

PMID- 24728612
TI  - Framework for the analysis of nanotechnologies' impacts and ethical
      acceptability: basis of an interdisciplinary approach to assessing novel
      technologies.
AB  - The genetically manipulated organism (GMO) crisis demonstrated that technological
      development based solely on the law of the marketplace and State protection
      against serious risks to health and safety is no longer a warrant of ethical
      acceptability. In the first part of our paper, we critique the implicitly
      individualist social-acceptance model for State regulation of technology and
      recommend an interdisciplinary approach for comprehensive analysis of the impacts
      and ethical acceptability of technologies. In the second part, we present a
      framework for the analysis of impacts and acceptability, devised-with the goal of
      supporting the development of specific nanotechnological applications-by a team
      of researchers from various disciplines. At the conceptual level, this analytic
      framework is intended to make explicit those various operations required in
      preparing a judgement about the acceptability of technologies that have been
      implicit in the classical analysis of toxicological risk. On a practical level,
      we present a reflective tool that makes it possible to take into account all the
      dimensions involved and understand the reasons invoked in determining impacts,
      assessing them, and arriving at a judgement about acceptability. 

PMID- 24728613
TI  - A phase IIa, nonrandomized study of radium-223 dichloride in advanced breast
      cancer patients with bone-dominant disease.
AB  - Radium-223 dichloride (radium-223) mimics calcium and emits high-energy, short
      range alpha-particles resulting in an antitumor effect on bone metastases. This
      open-label, phase IIa nonrandomized study investigated safety and short-term
      efficacy of radium-223 in breast cancer patients with bone-dominant disease.
      Twenty-three advanced breast cancer patients with progressive bone-dominant
      disease, and no longer candidates for further endocrine therapy, were to receive
      radium-223 (50 kBq/kg IV) every 4 weeks for 4 cycles. The coprimary end points
      were change in urinary N-telopeptide of type 1 (uNTX-1) and serum bone alkaline
      phosphatase (bALP) after 16 weeks of treatment. Exploratory end points included
      sequential (18)F-fluorodeoxyglucose positron emission tomography and computed
      tomography (FDG PET/CT) to assess metabolic changes in osteoblastic bone
      metastases. Safety data were collected for all patients. Radium-223 significantly
      reduced uNTX-1 and bALP from baseline to end of treatment. Median uNTX-1 change
      was -10.1 nmol bone collagen equivalents/mmol creatinine (-32.8 %; P = 0.0124);
      median bALP change was -16.7 ng/mL (-42.0 %; P = 0.0045). Twenty of twenty-three
      patients had FDG PET/CT identifying 155 hypermetabolic osteoblastic bone lesions
      at baseline: 50 lesions showed metabolic decrease (>=25 % reduction of maximum
      standardized uptake value from baseline) after 2 radium-223 injections [32.3 %
      metabolic response rate (mRR) at week 9], persisting after the treatment period
      (41.5 % mRR at week 17). Radium-223 was safe and well tolerated. Radium-223
      targets areas of increased bone metabolism and shows biological activity in
      advanced breast cancer patients with bone-dominant disease. 

PMID- 24728614
TI  - Coyotes, deer, and wildflowers: diverse evidence points to a trophic cascade.
AB  - Spatial gradients in human activity, coyote activity, deer activity, and deer
      herbivory provide an unusual type of evidence for a trophic cascade. Activity of
      coyotes, which eat young mule deer (fawns), decreased with proximity to a remote
      biological field station, indicating that these predators avoided an area of high
      human activity. In contrast, activity of adult female deer (does) and intensity
      of herbivory on palatable plant species both increased with proximity to the
      station and were positively correlated with each other. The gradient in deer
      activity was not explained by availabilities of preferred habitats or plant
      species because these did not vary with distance from the station. Does spent
      less time feeding when they encountered coyote urine next to a feed block,
      indicating that increased vigilance may contribute, along with avoidance of areas
      with coyotes, to lower herbivory away from the station. Judging from two
      palatable wildflower species whose seed crop and seedling recruitment were
      greatly reduced near the field station, the coyote-deer-wildflower trophic
      cascade has the potential to influence plant community composition. Our study
      illustrates the value of a case-history approach, in which different forms of
      ecological data about a single system are used to develop conceptual models of
      complex ecological phenomena. Such an iterative model-building process is a
      common, but underappreciated, way of understanding how ecological systems work.

PMID- 24728616
TI  - Risk of unplanned visits for colorectal cancer outpatients receiving
      chemotherapy: a case-crossover study.
AB  - AIM: This study was conducted to evaluate the impact of chemotherapy on the risk
      of unplanned visit in a cohort of colorectal cancer outpatients. Chief complaints
      for unplanned visits and risk factors for hospital admission were also analyzed.
      PATIENTS AND METHODS: Clinical data of 229 consecutive colorectal cancer patients
      who were unexpectedly presented to our acute oncology clinic between 2006 and
      2009 were reviewed. A case-crossover statistical analysis was applied to study
      the association between exposure to chemotherapy (trigger event) and the
      occurrence of unplanned visit (acute outcome) in three time windows (7, 15, and
      21 days from the closest previous chemotherapy treatment). Cox model was used to
      assess the risk factors for hospitalization. RESULTS: There were 469 unplanned
      visits registered. Most of the patients had Eastern Cooperative Oncology Group
      performance status (ECOG PS) 0-1 (80 %) and advanced cancer stage (78 %). The
      majority of unplanned visits (72 %) occurred within 30 days since last
      chemotherapy. The most frequent presenting complaints were pain, fatigue, and
      anorexia. The two time windows associated with higher risk of visit were 15 and
      21 days from last treatment, both for early (odds ratio [OR] 3.8, CI 1.4-10.2 and
      OR 3.8, CI 1.4-10.2) and advanced disease stage (OR 1.71, CI 1-2.9 and OR 3, CI
      1.5-5.9). Of the unplanned visits, 10 % resulted in hospital admission.
      Presenting with multiple symptoms and with deteriorated PS were both predictors
      for hospitalization. CONCLUSION: Chemotherapy exposition triggers the need for
      unplanned visits over the second and third week after treatment. The prompt and
      effective management of unexpected events may be cost- and time-saving and reduce
      pressure on oncology services.

PMID- 24728617
TI  - Health media use among childhood and young adult cancer survivors who smoke.
AB  - PURPOSE: Promoting healthy behaviors may reduce the risk of co-morbidities among
      childhood and young adult (CYA) cancer survivors. Although behavioral
      interventions are one way to encourage such activities, there is increasing
      evidence that health media use-particularly health information seeking-also may
      influence health knowledge, beliefs, and behaviors. The current study explores
      patterns of health media use among survivors of CYA cancer. Our focus is on
      survivors who smoke and thus are at even greater risk of co-morbidities. METHODS:
      We analyzed data from the Partnership for Health-2 study, a web-based smoking
      cessation intervention, to examine the prevalence of and factors associated with
      health media use (N = 329). RESULTS: Nearly two thirds (65.3 %) of CYA survivors
      who smoke reported infrequent or no online health information seeking. Many
      reported never reading health sections of newspapers or general magazines (46.2
      %) or watching health segments on local television news (32.3 %). Factors
      associated with health media use include education and employment, cancer-related
      distress, and smoking quit attempts. CONCLUSIONS: Health information engagement
      is low among CYA survivors who smoke, particularly active seeking of health
      information online. Population subgroups differ in their media use patterns; some
      of these differences reflect communication inequalities, which have the potential
      to exacerbate health disparities. Clinicians have an opportunity to guide CYA
      survivors towards useful and reliable information sources. This guidance could
      help survivors fulfill their unmet information and support needs and may be
      particularly important for less educated survivors and other underserved
      populations.

PMID- 24728619
TI  - Exploring the role of the partner in couples' sexual recovery after surgery for
      prostate cancer.
AB  - BACKGROUND: Prostate cancer survivors' post-surgery sexual problems are well
      documented and long lasting. Partners' distress in this context leads to
      psychological morbidity which is poorly understood. Given the prevalence of
      prostate cancer diagnoses in older men, partners' distress represents a public
      health concern. This study elucidates an important aspect of partners' distress
      which has hitherto been undocumented. It can lead to further research and health
      care provisions that will support couples in prostate cancer survivorship towards
      improved mental health and health outcomes. PURPOSE: Partner sexual function has
      been viewed as a factor in men's erectile function recovery after prostatectomy
      for prostate cancer. However, patients' and partners' perceptions on the role of
      the partner in couples' sexual recovery has not been studied. We wanted to
      understand those perceptions and to see whether their perceptions were congruent.
      METHODS: Men and partners were recruited from a previous study and interviewed
      separately about the role of the partner. Interview transcripts were analyzed
      using grounded theory with the help of NVivo software. RESULTS: Ten men and nine
      partners participated; most were more than 1 year past surgery. Men were 62, and
      partners were 58 years old on average. Nine men had erectile dysfunction. Six
      female partners were post-menopausal, and a participating male partner had post
      prostatectomy erectile dysfunction. Men and partners agreed that partners provide
      emotional and logistical support. Both perceived the partner's own sexual
      interest, not function, as critical to the couple's sexual recovery. Some men
      felt pressured by partners' initiative, feeling insecure about sexual
      performance. Men were unaware of partners' sexual needs or needs for support.
      Partners expressed those needs but were unsure of what kind of support they
      needed. CONCLUSION: Partners' sexual and support needs during couples' sexual
      recovery after prostatectomy should be acknowledged and addressed as a legitimate
      aspect of research and care for men recovering from prostatectomy.

PMID- 24728618
TI  - A systematic review on chronic oxaliplatin-induced peripheral neuropathy and the
      relation with oxaliplatin administration.
AB  - PURPOSE: The aim of this study was to systematically review the literature on the
      influence of oxaliplatin administration (e.g. cumulative dose, dose intensity,
      number of cycles and combination regimen) on the long-term prevalence of
      oxaliplatin-induced peripheral neuropathy (O-IPN) at least 12 months after
      termination of chemotherapy. METHODS: A computerized search of literature on
      databases PubMed and Cochrane was performed. Published original articles were
      included if they reported about long-term O-IPN and gave concomitant information
      about oxaliplatin therapy given to the patients. All articles were assessed for
      quality. RESULTS: We included 14 articles (n=3,869 patients), and the majority of
      these studies were of high quality. All included patients who were treated for
      colorectal cancer, mainly with oxaliplatin in combination with 5
      fluorouracil/leucovorin. Median cumulative doses and dose intensity varied
      between 676 and 1,449 mg/m2 and 30.8 and 42.6 mg/m2/week, respectively.
      Neuropathy assessment differed between studies, and the National Cancer Institute
      Common Terminology Criteria (NCI-CTC) was used most often. The degree of
      neuropathy ranged from grade 0 to 3. Only six studies directly assessed the
      relationship between oxaliplatin administration and neuropathy. Of these studies,
      five did find a relation between neuropathy and higher cumulative dose, while one
      study did not find a relation. CONCLUSIONS: O-IPN is still present in a great
      amount of patients in >=12 months after termination of therapy. A higher
      cumulative dose is likely to have an influence on the development of long-term O
      IPN. More studies are needed that assess long-term neuropathy and oxaliplatin
      administration by means of validated neuropathy assessments.

PMID- 24728620
TI  - An investigation of the colorectal cancer experience and receptivity to family
      based cancer prevention programs.
AB  - PURPOSE: Cancer is a shared family experience and may provide a "teachable
      moment" to motivate at-risk family members to adopt cancer prevention and health
      promotion behaviors. This study explored how a diagnosis of colorectal cancer
      (CRC) is experienced by family members and may be used to develop a family-based
      CRC prevention program. Preferences regarding content, timing, and modes of
      program delivery were examined. Social cognitive theory provided the conceptual
      framework for the study. METHODS: This study employed mixed methodology (semi
      structured interviews and self-report questionnaires). Participants included 73
      adults (21 patients, 52 family members) from 23 families (two patients were
      deceased prior to being interviewed). Most patients (n = 14; 67 %) were
      interviewed 1-5 years post-diagnosis. Individual interviews were audio-recorded,
      transcribed, and content analyzed. RESULTS: For many, a CRC diagnosis was
      described as a shared family experience. Family members supported each other's
      efforts to prevent CRC through screening, exercising, and maintaining a healthy
      diet. Teachable moments for introducing a family-based program included the time
      of the patient's initial cancer surgery and post-chemotherapy. Reported
      willingness to participate in a family-based program was associated with risk
      perception, self-efficacy, outcome expectancies, and the social/community context
      in which the program would be embedded. Program preferences included cancer
      screening, diet/nutrition, weight management, stress reduction, and exercise.
      Challenges included geographic dispersion, variation in education levels,
      generational differences, and scheduling. CONCLUSIONS: CRC patients and family
      members are receptive to family-based programs. Feasibility concerns, which may
      be mitigated but not eliminated with technological advances, must be addressed
      for successful family-based programs.

PMID- 24728622
TI  - Retraction note to: Aging decreases rate of docosahexaenoic acid synthesis
      secretion from circulating unesterified alpha-linolenic acid by rat liver. Age
      (2012) 35(3): 597-608.

PMID- 24728621
TI  - Levels and correlates of knowledge about Alzheimer's disease among older Chinese
      Americans.
AB  - OBJECTIVE: This study examined knowledge of Alzheimer's disease (AD) and
      correlates of AD knowledge in a sample of Chinese American older adults living in
      the Phoenix metropolitan area of the United States. METHODS: Survey data were
      collected from 385 Chinese Americans age 55 or older (M = 72.43, SD = 8.67)
      recruited from various settings not limited to senior housing facilities, senior
      clubs, senior centers and church groups. RESULTS: Participants responded to a 24
      item true/false AD knowledge scale with 73 % accuracy. Multivariate regression
      analyses found that participants who held more traditional Chinese cultural
      beliefs of AD tended to have less AD knowledge. Older women had more knowledge of
      AD than men when educational differences were controlled. Participants who used
      media to acquire AD information had more AD knowledge than those did not.
      CONCLUSIONS: AD educational programs should target domains (e.g., risk factors,
      symptoms, and caregiving) about which Chinese American elders tend to have less
      knowledge; AD information should be disseminated through appropriate media to
      outreach Chinese American elders more effectively. Addressing the biases in
      elders' cultural beliefs of AD should be incorporated in AD educational programs.

PMID- 24728624
TI  - Combining experiment and theory to elucidate the role of supercritical water in
      sulfide decomposition.
AB  - The cleavage of C-S linkages plays a key role in fuel processing and organic
      geochemistry. Water is known to affect these processes, and several hypotheses
      have been proposed, but the mechanism has been elusive. Here we use both
      experiment and theory to demonstrate that supercritical water reacts with
      intermediates formed during alkyl sulfide decomposition. During hexyl sulfide
      decomposition in supercritical water, pentane and CO + CO2 were detected in
      addition to the expected six carbon products. A multi-step reaction sequence for
      hexyl sulfide reacting with supercritical water is proposed which explains the
      surprising products, and quantum chemical calculations provide quantitative rates
      that support the proposed mechanism. The key sequence is cleavage of one C-S bond
      to form a thioaldehyde via radical reactions, followed by a pericyclic addition
      of water to the C[double bond, length as m-dash]S bond to form a geminal
      mercaptoalcohol. The mercaptoalcohol decomposes into an aldehyde and H2S either
      directly or via a water-catalyzed 6-membered ring transition state. The aldehyde
      quickly decomposes into CO plus pentane by radical reactions. The time is ripe
      for quantitative modelling of organosulfur reaction kinetics based on modern
      quantum chemistry. 

PMID- 24728623
TI  - Effects of acute bouts of endurance exercise on retinal vessel diameters are age
      and intensity dependent.
AB  - Alterations of retinal vessel diameters are associated with increased
      cardiovascular risk. We aimed to investigate changes in retinal vessel diameters
      in response to acute dynamic exercise of different intensities and whether these
      changes are age dependent. Seventeen healthy seniors (median (IQR) age 68 (65,
      69) years) and 15 healthy young adults (median (IQR) age 26 (25, 28) years) first
      performed a maximal treadmill test (MTT) followed by a submaximal treadmill test
      (SMTT) and a resting control condition in randomised order. Central retinal
      arteriolar (CRAE) and central retinal venular (CRVE) diameter equivalents were
      measured before as well as 5 (t5) and 40 (t40) minutes after exercise cessation
      using a static retinal vessel analyser. Both exercise intensities induced a
      significant dilatation in CRAE and CRVE at t5 compared to the control condition
      (P < 0.001). At t40, the mean increase in CRAE and CRVE was greater for MTT
      compared to that for SMTT (CRAE 1.7 MUm (95 % confidence interval (CI) -0.1, 3.6;
      P = 0.061); CRVE 2.2 MUm (95 % CI 0.4, 4.1; P = 0.019)). However, the estimated
      difference at t5 between seniors and young adults in their response to MTT
      compared to SMTT was 5.3 MUm (95 % CI 2.0, 8.5; P = 0.002) for CRAE and 4.1 MUm
      (95 % CI -0.4, 8.6; P = 0.076) for CRVE. Wider arteries and veins after maximal
      versus submaximal exercise for seniors compared to young adults suggest that
      myogenic vasoconstriction in response to exhaustive exercise may be reduced in
      seniors. Age-related loss of vascular reactivity has clinical implications since
      the arteriolar vasoconstriction protects the retinal capillary bed from
      intraluminal pressure peaks.

PMID- 24728625
TI  - Surgical decision-making for managing complex intracranial aneurysms.
AB  - The treatment of complex intracranial aneurysms remains a therapeutic challenge.
      These lesions are frequently not amenable to selective clipping or coiling or
      other endovascular procedures and surgery still has a predominant role.We
      illustrate our "surgical decision making" for managing complex intracranial
      aneurysmal lesions. The best strategy is decided on the basis of pre-operative
      neuroradiological and intra-operative main determinants such as anatomical
      location, peri-aneurysmal angioanatomy (branch vessels, critical perforators),
      broad neck, intraluminal thrombosis, aneurysmal wall atherosclerotic plaques and
      calcifications, absence of collateral circulation, and previous treatment. The
      surgical strategy encompasses one of the following treatment possibilities: (1)
      Direct clip reconstruction; (2) Complete trapping ("classic" or "variant"); (3)
      Partial trapping (proximal "inflow" or distal "outflow" occlusion). Because the
      goal of any aneurysm treatment is both (1) aneurysm exclusion and (2) blood flow
      replacement, cerebral revascularization represents a major management option
      whenever definitive or temporary vessel occlusion is needed.Cerebral
      revascularization can therefore be used temporarily as a "protective" bypass, or
      definitively as a "flow replacement" bypass.Complete and partial trapping
      strategies are associated with flow "replacement" bypass surgery, to preserve
      blood flow into the territory supplied by the permanently trapped vessel. The
      construction of the "ideal" bypass depends on several factors, the most important
      of which are amount of flow needed, recipient vessel, donor vessel, and
      microanastomosis technique.The choice between "complete" or "partial" trapping
      depends on angioanatomical criteria as well. A complete trapping is always
      favored, as it has the advantage of immediate aneurysm exclusion. When
      perforating vessels arise from the aneurysmal segment or when the inspection of
      all the angioanatomy of the aneurysm is considered inadvisable and risky,
      "partial trapping" strategies are of interest. Partial trapping may consist
      either of proximal or distal occlusion. We discuss the rationale behind these
      treatment modalities and illustrate it with a case series of seven patients
      successfully treated for complex intracranial aneurysmal lesions (location: 1
      ICA, 1 ACom, 3 MCA, 2 PICA). 

PMID- 24728626
TI  - Recurrent and incompletely treated aneurysms.
AB  - Endovascular treatment of intracranial aneurysms has become an established
      technique that can provide stable permanent occlusion in over 85 % of the cases.
      Even those aneurysms considered untreatable by endovascular means can now often
      be managed by the use of adjunctive measures, e.g., balloon protection devices,
      intracranial stents, and semipermeable stents, i.e., "flow diverters." In those
      cases, in which relevant aneurysm recurrences are documented upon angiographic
      follow-up, both endovascular and surgical techniques can be employed. In rare
      cases, combined treatment strategies including parent artery occlusion under
      bypass protection can be performed. At our center, the majority of relevant
      aneurysm recurrences after initial coil embolization are managed by a second
      endovascular procedure. In some cases, e.g., aneurysm recurrences not feasible
      for endovascular re-treatment, documented aneurysmal growth, bleeding from a
      previously embolized aneurysm, and acute hemorrhagic or ischemic complications
      during endovascular procedures, surgical management may be necessary. This report
      briefly outlines the most frequent treatment scenarios. 

PMID- 24728627
TI  - The Mini Supra-orbital Approach for Cerebral Aneurysm of the Anterior Portion of
      the Circle of Willis.
AB  - OBJECTIVES: Various mini-invasive approaches have been developed over the last
      decade to expose the suprasellar area. The supraorbital approach takes a
      predominant place in exposing the suprasellar area and the Sylvian fissure.
      OPERATIVE TECHNIQUE: Based on our surgical experience, the technique of
      supraorbital subfrontal approach is described in detail in this article. After an
      eyebrow incision, a small frontal craniotomy was performed. Indications,
      advantages and limitations: This mini-invasive approach was indicated for
      patients with unruptured aneurysm, in patients with aneurysmal SAH without
      intracranial hypertension, and especially in elderly patients. This
      minicraniotomy (1) gave quick and direct access to the aneurysm; (2) provided
      less trauma of the temporal muscle and improved the cosmetic resuilts; and (3)
      reduced the risk of postoperative epidural hematoma thanks to the small
      detachment of the dura mater from the vault. CONCLUSION: We concluded that this
      limited supraorbital approach gave adequate visualization and allows surgical
      manipulation within eloquent structures and can be specifically applied in
      absence of intracranial hypertension.

PMID- 24728628
TI  - Surgical exclusion of unruptured middle cerebral artery aneurysms: experience of
      126 cases.
AB  - A group of 126 surgical patients with 143 unruptured MCA aneurysms was evaluated
      in order to determine the risks of treatment and possible adjuncts for safer
      surgery. The precise location and size of the aneurysms were determined in each
      case; 21 aneurysms were located on the M1 tract, 109 on the main division - which
      consisted of more than two branches in 10 cases and was proximally located in 12
      cases - and 13 were distal; 36 aneurysms were small (<7 mm), 90 standard, and 17
      large or giant (>15 mm); 45 patients harbored multiple aneurysms (12 on the
      ipsilateral MCA). The aneurysms were excluded by clip in most cases, with the
      assistance of intraoperative flowmetry in 78 patients. Temporary proximal vessel
      occlusion was used in 57 patients (>10 min in 8 cases), without significant
      effects on radiological or clinical outcome. After surgery, newly occurring minor
      deficits were observed in 5 patients and significant deficits in 4; one patient
      died from an intractable coagulopathy. The low rate (3.9 %) of unfavorable
      results (modified Rankin Score > 2) linked to surgery justifies serious
      consideration for treatment in these patients, especially when facing the high
      disability rate after the rupture of aneurysms in this anatomical location. 

PMID- 24728629
TI  - Progress in the treatment of unruptured aneurysms.
AB  - Recent technological progress has reduced the complication rate of unruptured
      aneurysm. We treated 128 unruptured aneurysms between April 2006 and March 2012.
      Seventy-six aneurysms (59 %) were clipped and 52 (41 %) were coil embolized.
      After 2010, we applied new instruments, i.e., near-infrared indocyanine-green
      videoangiography (ICG), an intraoperative endoscope, preoperative detailed MRI,
      and a stent-assisted coil embolization. In the results: (1) In 60 aneurysms
      treated before 2009, three patients showed a deterioration of more than two
      points in mRS (5 %). In 68 aneurysms treated after 2010, no patients showed
      deterioration (0 %) (p: n.s.). (2) No patients died and 126 patients (98 %) were
      discharged to home directly. (3) No patients showed rupture after treatment. In
      conclusion, the appropriate selection of treatment and recent technological
      progress have facilitated sophisticated treatment of unruptured aneurysms.
      Recently, the complication rate in surgery and endovascular surgery for
      unruptured aneurysms has become acceptably low. 

PMID- 24728630
TI  - Distal basilar artery aneurysms: conditions for safe and secure clipping.
AB  - In general, vertebro-basilar aneurysms are good indications for endovascular
      treatment. However, basilar artery (BA) bifurcation aneurysms, BA-superior
      cerebellar artery (SCA) aneurysms, and sometimes mid-basilar aneurysms are also
      good indications for clipping. In this paper, conditions for safe and secure
      clipping for distal basilar aneurysms are discussed.There are several tips for
      the clipping of distal BA aneurysms. Among them, the following are very
      important: patency of the perforators, posterior cerebral artery (P1), and SCA
      must always be maintained. Several modalities including micro-Doppler
      ultrasonography and indocyanine green video-angiography (ICGVA) should be used to
      confirm the patency of these vessels. Each confirmation of patency of the vessels
      after clipping must be compared to those from before the clipping. Intra
      operative digital subtraction angiography (DSA) is needed for large or giant
      aneurysms. 

PMID- 24728631
TI  - Role of bypass surgery and balloon occlusion test for the endovascular management
      of fusiform dissecting aneurysms. Report of two cases.
AB  - Fusiform intracranial aneurysm is one of the most difficult pathologies to treat.
      The role and efficacy of recent advanced endovascular technique and conventional
      bypass surgery are discussed. 

PMID- 24728632
TI  - Analysis of combined coiling and neuroendoscopy in the treatment of
      intraventricular hemorrhage due to ruptured aneurysm.
AB  - BACKGROUND: Subarachnoid hemorrhage (SAH) with intraventricular hemorrhage (IVH)
      is associated with poor outcomes. The aim of this study was to evaluate the
      effectiveness of combined coiling and neuroendoscopy to treat severe SAH with
      massive IVH. METHOD: Between April 2008 and March 2012, 13 patients had massive
      IVH with a ruptured aneurysm treated at the Department of Neurosurgery, Fukuoka
      University, Japan. All 13 patients were treated within 2 days of onset by coiling
      and neuroendoscopic removal of the IVH, including the fourth ventricle. RESULTS:
      No rebleeding or acute hydrocephalus were noted. Glasgow Outcome Scale scores
      (GOS) at discharge were: good recovery (two patients), moderate disability (three
      patients), severe disease (one patient), vegetative state (four patients), and
      dead (three patients). A good modified Rankin Scale score (mRS) (0-2) at 6 months
      was observed in six patients and a poor mRS score (3-6) occurred in seven. The
      pre- and post-operative Graeb scores were significantly lower in the good mRS
      group (p = 0.020 and 0.033, respectively, Mann-Whitney U-test). GOS scores at
      discharge were significantly associated with mRS score at 6 months (p = 0.011,
      Fisher's Exact Test). CONCLUSIONS: Combined coiling and neuroendoscopic removal
      of the IVH, including the fourth ventricle, were feasible procedures and achieved
      preferable outcomes in approximately half of the cases.

PMID- 24728633
TI  - Intracranial hypertension in subarachnoid hamorrhage: outcome after decompressive
      craniectomy.
AB  - Intracranial hypertension can occur following aneurysmal subarachnoid haemorrhage
      (SAH). It can be treated with decompressive craniectomy (DC) with the aim of
      reducing intracranial pressure, increasing cerebral perfusion and reducing
      further morbidity and mortality. We studied the outcome of patients undergoing DC
      following SAH at our institution, to ascertain whether the use of this treatment
      can be rationalized. 

PMID- 24728634
TI  - Selective Targeted Cerebral Revascularization via Microscope Integrated
      Indocyanine Green Videoangiography Technology.
AB  - Protective or flow replacement bypass surgery has an important role in the
      management of complex middle cerebral artery (MCA) aneurysms. Protective bypass
      is useful when prolonged temporary arterial occlusion is needed for clip
      reconstruction. Flow replacement bypass is instead important when aneurysmal
      trapping is the treatment of choice in order to supply permanent collateral blood
      flow to the brain distal to the "trapped" vessel. In both cases, the
      identification of the correct recipient artery is an essential surgical step.
      When a superficial (cortical) artery is chosen as recipient, it indeed has to
      represent a distal branch of the involved (temporarily or permanently occluded)
      vessel.Here we describe a technique for selective-targeted revascularization
      based on the use of indocyanine green video angiography (ICG-VA), a microscope
      integrated intraoperative tool nowadays known to provide real-time assessment of
      the cerebral circulation with distinct visualization of arterial, capillary and
      venous angiographic phases. The technique is founded on the analysis of
      differences in the timing of filling of M4 vessels seen on serial ICG-VAs. It
      enables reliable identification of the cortical recipient and eliminates the risk
      of erroneous revascularization of non-involved territories. The surgical decision
      making of two patients treated for complex MCA aneurysms with selective-targeted
      bypass is presented. 

PMID- 24728635
TI  - Combined Bypass Technique for Contemporary Revascularization of Unilateral MCA
      and Bilateral Frontal Territories in Moyamoya Vasculopathy.
AB  - Moyamoya vasculopathy (MMV) leads to chronic hypoperfusion predominantly in the
      middle cerebral artery (MCA) and anterior cerebral artery (ACA) territories. Most
      revascularization techniques focus on revascularization of the MCA territory.
      Augmentation of blood flow in the frontal area is important for neurocognition
      and lower extremity function. In this article we describe a new combined (direct
      and indirect) one-stage bypass technique consisting of a superficial temporal
      artery to middle cerebral artery (STA-MCA) bypass with encephalo-duro-synangiosis
      (EDS) for unilateral MCA revascularization, along with an encephalo-duro
      periosteal-synangiosis (EDPS) for bifrontal blood flow augmentation. The strength
      of this technique is the revascularization of three vascular territories during a
      single surgical intervention: the MCA unilaterally; and the frontal territories
      bilaterally. Bifrontal EDPS may also be considered as a supplementary independent
      procedure for patients who previously underwent revascularization treatment in
      the MCA territory, but develop symptoms due to frontal hypoperfusion. 

PMID- 24728636
TI  - "How I Do It:" Non-occlusive High Flow Bypass Surgery.
AB  - Giant intracranial aneurysms are a formidable challenge for treatment,
      considering their grim prognosis. Until lately, endovascular treatment options
      have been disappointing, and neurosurgical treatment results are by far the most
      promising. In the neurosurgical treatment of giant intracranial aneurysms, the
      non-occlusive nature of the ELANA anastomosis technique is a major advantage in
      flow replacement bypass surgery where large proximal arteries with higher flows
      need to be replaced or reconstructed. The construction of a deep intracranial
      anastomosis using the ELANA technique needs less vessel exposure than when using
      a conventional occlusive technique. This extra advantage facilitates the
      construction of anastomoses even on the ICA, MCA, ACA, P1, P2, SCA or BA, using
      the trans-Sylvian route only, without major skull base surgery. Several different
      types of EC-IC and IC-IC flow replacement bypass are now safely applicable due to
      the non-occlusive character of this technique.Future improvements of the
      technique are focused on sutureless applications, graft improvements and Flow
      Model Simulation. It is clear that not only conventional bypass techniques, but
      also, and even especially, the ELANA bypass technique, are of great value in the
      treatment of giant aneurysms. 

PMID- 24728637
TI  - The Role of MCA-STA Bypass Surgery After COSS and JET: The European Point of
      View.
AB  - The results of the previously published Carotid Occlusion Surgery Study (COSS)
      and the Japanese EC-IC Bypass Trial (JET) seem to influence the position towards
      surgical treatment for ischemic cerebrovascular disease (Ogasawara and Ogawa,
      Nihon Rinsho 64(Suppl 7):524-527, 2006; Powers et al., JAMA 306:1983-1992,
      2011).The goal of this article is to give the European point of view after COSS
      and JET on behalf of the Cerebrovascular Section of the European Association of
      Neurological Surgeons (EANS). 

PMID- 24728638
TI  - STA-MCA/STA-PCA Bypass Using Short Interposition Vein Graft.
AB  - BACKGROUND AND AIMS: Superficial temporal artery (STA) is the mainstay of donor
      vessels for extra-intracranial bypass (EC-IC bypass) in cerebral
      revascularization. However, the typically used STA frontal or parietal branch is
      not always adequate in its flow-carrying capacity. In the present study, we
      provide an update on an alternative strategy: the use of the STA main trunk as a
      donor vessel, with a short vein interposition graft. METHODS: Seven patients in
      whom the STA main trunk was used as a donor site for anastomosis of a short
      interposition vein graft were included. The grafts were implanted into the M2 of
      the middle cerebral artery for adjunctive treatment of IC anterior wall blood
      blister aneurysms in two patients, for revascularization of an internal carotid
      artery occlusion in one patient, into the P2/3 of the posterior cerebral artery
      (PCA) for adjunct treatment of complex PCA aneurysms in three patients and into
      the P3 of PCA for adjunct treatment of basilar artery (BA) trunk giant aneurysm
      in one patient. RESULTS: All the bypasses were patent. Intraoperative flow
      measurements confirmed a moderate flow-carrying capacity of the STA main trunk
      interposition short vein graft (20-50 ml; mean 43 ml/min). CONCLUSION: The STA
      main trunk has a larger diameter than the distal branch; therefore, it would be
      expected to have a significantly higher flow capacity than its branches. STA main
      trunk to proximal MCA/PCA bypass using short interposition vein grafts can
      provide sufficient blood flow, and may be a reasonable alternative to ECA to
      MCA/PCA bypass using long vein grafts.

PMID- 24728639
TI  - Endovascular treatment for intracranial vertebrobasilar artery stenosis.
AB  - PURPOSE: We describe our experience with endovascular treatment for symptomatic
      intracranial vertebrobasilar artery stenosis. MATERIALS AND METHODS: Forty-four
      patients with intracranial vertebrobasilar artery stenosis (37 vertebral
      arteries, 7 basilar arteries) were treated with endovascular surgery. Indication
      criteria for the treatment were (1) medically refractory symptomatic patients;
      (2) angiographic stenosis of more than 60 %; and (3) short lesion (<15 mm). Under
      local anesthesia, balloon angioplasty was first performed in all patients.
      Stenting was performed only in cases with insufficient dilatation, dissection, or
      restenosis after balloon angioplasty. The degree of stenosis, which was 83 %
      before treatment, was reduced to 23 % after treatment. The rate of stroke and
      death within 30 days was 2.3 %. Nine patients (20.5 %) developed restenosis
      within 6 months. Of these, four patients were symptomatic. All symptomatic
      patients with restenosis were successfully treated with balloon angioplasty or
      stenting. CONCLUSION: Endovascular treatment for vertebrobasilar artery stenoses
      is feasible and safe in selected patients. Restenosis may be an important cause
      of recurrent stroke. Therefore, close clinical and neuroradiological follow-ups
      are essential for patients treated with endovascular surgery to improve long-term
      results.

PMID- 24728640
TI  - Carotid Endarterectomy for Pseudo-occlusion of the Cervical Internal Carotid
      Artery.
AB  - OBJECT: This study described clinicopathological characteristics of pseudo
      occlusion (PO) of the internal carotid artery (ICA) with regards to the
      pathological mechanism and the benefit of carotid endarterectomy (CEA). METHODS:
      We retrospectively reviewed 17 PO patients who underwent CEA. Clinical
      presentation, angiographic findings, surgical outcomes and plaque components
      obtained from CEA were investigated. RESULTS: PO plaques had more fibrous and two
      different pathological features, including total occlusion with recanalization
      and severe stenosis. Plaques of the total occlusion with recanalization (8
      patients) were composed of thrombotic total occlusion and lumen recanalization by
      large neovascular channels, whereas those with severe stenosis (9 patients) were
      fibrous or fibroatheromatous plaque with severe stenosis of the original lumen.
      Of all the patients who underwent a carotid angiogram 2 weeks after surgery, 16
      were successfully treated, but one showed complete occlusion of the ICA. At the
      follow-up period, two patients showed restenosis of the ICA. Three patients with
      complete occlusion or restenosis had histologically fibrous sclerotic plaques.
      CONCLUSION: Patients with PO had more fibrous plaques and two different
      histological features, including total occlusion with recanalization or severe
      stenosis. The plaque histology may be related to the pathogenesis and the
      surgical outcome.

PMID- 24728641
TI  - Identification of plaque location using indocyanine green videoangiography during
      carotid endarterectomy.
AB  - BACKGROUND AND AIMS: The aim of the present study was to assess whether surgical
      microscope-based indocyanine green (ICG) videoangiography (ICG-VA) using FLOW 800
      software provides useful evaluation of blood flow during carotid endarterectomy
      (CEA). METHODS: Twenty CEA procedures were performed in 19 patients between July
      2011 and January 2012. ICG was injected intravenously before and after CEA, and
      ICG-VA video sequences were analyzed using FLOW 800. Regions of interest were
      identified in the common carotid artery, plaque, internal carotid artery, and
      external carotid artery, and changes in intensity values were evaluated. RESULTS:
      The distal and proximal ends of the carotid plaque were identified in 87.5 and 75
      % of cases, respectively. After CEA, intensity values in the common carotid
      artery, plaque, internal carotid artery, and external carotid artery had
      increased by 162 +/- 129, 337 +/- 212, 139 +/- 151, and 177 +/- 143,
      respectively. The intensity values in the region of the plaque showed the
      greatest improvement. CONCLUSIONS: ICG-VA can provide information regarding
      plaque location vessel patency during CEA. FLOW 800 software provides
      semiquantitative information regarding blood flow, especially in cases of severe
      stenosis with collapse of the internal carotid artery.

PMID- 24728642
TI  - Surgery after embolization of cerebral arterio-venous malformation: experience of
      123 cases.
AB  - A group of 123 patients with large or critically located arterio-venous
      malformations (AVMs), operated on between 1990 and 2011 and who underwent
      preoperative embolization, was assessed in order to clarify the risks of this
      combined treatment. AVM location, volume, and Spetzler's grade were assessed in
      each case; AVM volume was over 20 cm(3) in 49 % of the cases; Spetzler's grade
      was 3 or above in 76 % of the cases (with 34 cases in grades 4-5). A mean of 2.3
      embolization procedures per patient were carried out, using bucrylate and, more
      recently, Onyx and/or Glubran; a 4.5 % procedure-related complication rate was
      observed. Complications occurring after surgery were classified as hemorrhagic
      (16 cases, 8 requiring surgical evacuation) or ischemic (4 cases); hemorrhagic
      complications were more common for AVMs with volumes >20 cm(3) and/or deep
      feeders. Surgery-related unfavorable results (modified Rankin Score > 2) were
      observed in 6 % of patients in Spetzler's grade 3, and in 20-25 % of patients in
      grades 4-5. More recently, a triple treatment (radiosurgery + embolization +
      surgery) allowed for obtaining favorable results (mRS 0-2) in all patients. It
      has been concluded that a combined treatment with embolization and surgery
      constitutes a reasonable choice for complex cerebral AVMs; the association of
      radiosurgery may improve the patients outcome. 

PMID- 24728643
TI  - Epilepsy and headache after resection of cerebral arteriovenous malformations.
AB  - The therapeutic benefits of microsurgery for cerebral arteriovenous malformations
      (AVM) with regard to headache and epilepsy are not well known. The objective of
      the present review is to discuss the available evidence and our own experience,
      which showed that two-thirds of the patients with preoperative epilepsy
      experienced long-term improvement, one-sixth no significant change, and an equal
      number worsening. New seizures occurred postoperatively in 18 % of the patients
      presenting with hemorrhage. Regarding headache, 40 % of patients with
      preoperative chronic headache reported improvement and 50 % described no change,
      whereas 10 % suffered from deterioration. With regard to epilepsy, the available
      literature suggests, that an epileptological approach with preoperative
      identification of the seizure focus and corresponding resection might improve the
      results. With regard to headache outcome, almost no information is available in
      the literature, suggesting that these complaints of the patients have so far not
      received the necessary attention. In conclusion, the long-term treatment results
      regarding chronic epilepsy and chronic headache need further study and
      optimization. 

PMID- 24728644
TI  - Results of surgery for cavernomas in critical supratentorial areas.
AB  - A total of 121 patients surgically treated between 1991 and 2011 for cavernomas
      in critical supratentorial areas were evaluated. Anatomical location, size and
      the possible association with developmental venous anomalies (DVA) were assessed
      in each case: 43 cavernomas were in the speech area, 39 were rolandic (or peri
      rolandic), 14 insular, 10 nuclear, 9 calcarine and 6 ventricular. In 49 % of the
      cases, the cavernoma was <1.5 cm; in 6 patients, radiological growth was
      documented. A method of intraoperative localization was adopted in 78 cases: B
      mode echography or a stereotactic guide in 22 cases, and a neuronavigation system
      in 56 cases; preoperative angiography was done in 22 cases. Early postoperative
      epilepsy (within 7 days of surgery) was observed in 15 cases. As for clinical
      outcome, 14 patients presented with mild symptoms (modified Rankin Scale 1-2);
      significant deficits occurred ex-novo in 5 patients. The presence of epilepsy at
      follow-up was assessed through the Maraire Scale: 44 % of patients presenting
      with epilepsy were free of seizures and without therapy at a mean follow-up of
      4.6 years, and an additional 55 % had complete control of seizures with therapy.
      It is concluded that surgery is indicated in the management of cavernomas in
      critical supratentorial locations, with a caveat for insula and especially basal
      ganglia. 

PMID- 24728645
TI  - High resolution imaging of cerebral small vessel disease with 7 T MRI.
AB  - Small vessel disease (SVD) refers to all pathological processes that affect the
      small vessels of the brain. SVD is an important cause of acute stroke, but is
      also a leading cause of aging-related cognitive decline and dementia, due to more
      insidious brain parenchymal damage. The introduction of high field strength MRI
      (7 T) is likely to offer important new perspectives on the role of SVD in these
      disorders. In this overview we illustrate the opportunities that 7 T MRI offers
      in high resolution vascular imaging. In particular, we will show the capability
      of 7 T MRI to depict the small arteries and veins in the brain, the vascular wall
      of intracranial arteries, perivascular spaces, and microvascular parenchymal
      lesions, including microbleeds and microinfarcts. 

PMID- 24728646
TI  - Boom-Bust Turnovers of Megabase-Sized Centromeric DNA in Solanum Species: Rapid
      Evolution of DNA Sequences Associated with Centromeres.
AB  - Centromeres are composed of long arrays of satellite repeats in most
      multicellular eukaryotes investigated to date. The satellite repeat-based
      centromeres are believed to have evolved from "neocentromeres" that originally
      contained only single- or low-copy sequences. However, the emergence and
      evolution of the satellite repeats in centromeres has been elusive. Potato
      (Solanum tuberosum) provides a model system for studying centromere evolution
      because each of its 12 centromeres contains distinct DNA sequences, allowing
      comparative analysis of homoeologous centromeres from related species. We
      conducted genome-wide analysis of the centromeric sequences in Solanum
      verrucosum, a wild species closely related to potato. Unambiguous homoeologous
      centromeric sequences were detected in only a single centromere (Cen9) between
      the two species. Four centromeres (Cen2, Cen4, Cen7, and Cen10) in S. verrucosum
      contained distinct satellite repeats that were amplified from retrotransposon
      related sequences. Strikingly, the same four centromeres in potato contain either
      different satellite repeats (Cen2 and Cen7) or exclusively single- and low-copy
      sequences (Cen4 and Cen10). Our sequence comparison of five homoeologous
      centromeres in two Solanum species reveals rapid divergence of centromeric
      sequences among closely related species. We propose that centromeric satellite
      repeats undergo boom-bust cycles before a favorable repeat is fixed in the
      population.

PMID- 24728647
TI  - Efficient Genome-Wide Detection and Cataloging of EMS-Induced Mutations Using
      Exome Capture and Next-Generation Sequencing.
AB  - Chemical mutagenesis efficiently generates phenotypic variation in otherwise
      homogeneous genetic backgrounds, enabling functional analysis of genes. Advances
      in mutation detection have brought the utility of induced mutant populations on
      par with those produced by insertional mutagenesis, but systematic cataloguing of
      mutations would further increase their utility. We examined the suitability of
      multiplexed global exome capture and sequencing coupled with custom-developed
      bioinformatics tools to identify mutations in well-characterized mutant
      populations of rice (Oryza sativa) and wheat (Triticum aestivum). In rice, we
      identified ~18,000 induced mutations from 72 independent M2 individuals.
      Functional evaluation indicated the recovery of potentially deleterious mutations
      for >2600 genes. We further observed that specific sequence and cytosine
      methylation patterns surrounding the targeted guanine residues strongly affect
      their probability to be alkylated by ethyl methanesulfonate. Application of these
      methods to six independent M2 lines of tetraploid wheat demonstrated that our
      bioinformatics pipeline is applicable to polyploids. In conclusion, we provide a
      method for developing large-scale induced mutation resources with relatively
      small investments that is applicable to resource-poor organisms. Furthermore, our
      results demonstrate that large libraries of sequenced mutations can be readily
      generated, providing enhanced opportunities to study gene function and assess the
      effect of sequence and chromatin context on mutations.

PMID- 24728648
TI  - HEAT-INDUCED TAS1 TARGET1 Mediates Thermotolerance via HEAT STRESS TRANSCRIPTION
      FACTOR A1a-Directed Pathways in Arabidopsis.
AB  - Many heat stress transcription factors (Hsfs) and heat shock proteins (Hsps) have
      been identified to play important roles in the heat tolerance of plants. However,
      many of the key factors mediating the heat response pathways remain unknown.
      Here, we report that two genes, which are targets of TAS1 (trans-acting siRNA
      precursor 1)-derived small interfering RNAs that we named HEAT-INDUCED TAS1
      TARGET1 (HTT1) and HTT2, are involved in thermotolerance. Microarray analysis
      revealed that the HTT1 and HTT2 genes were highly upregulated in Arabidopsis
      thaliana seedlings in response to heat shock. Overexpression of TAS1a, whose
      trans-acting small interfering RNAs target the HTT genes, elevated accumulation
      of TAS1-siRNAs and reduced expression levels of the HTT genes, causing weaker
      thermotolerance. By contrast, overexpression of HTT1 and HTT2 upregulated several
      Hsf genes, leading to stronger thermotolerance. In heat-tolerant plants
      overexpressing HsfA1a, the HTT genes were upregulated, especially at high
      temperatures. Meanwhile, HsfA1a directly activated HTT1 and HTT2 through binding
      to their promoters. HTT1 interacted with the heat shock proteins Hsp70-14 and
      Hsp40 and NUCLEAR FACTOR Y, SUBUNIT C2. Taken together, these results suggest
      that HTT1 mediates thermotolerance pathways because it is targeted by TAS1a,
      mainly activated by HsfA1a, and acts as cofactor of Hsp70-14 complexes.

PMID- 24728649
TI  - The benefit of attention is not diminished when distributed over two simultaneous
      cues.
AB  - Recent findings have suggested that transient attention can be triggered at two
      locations simultaneously. However, it is unclear whether doing so reduces the
      effect of attention at each attended location. In two experiments, we explored
      the consequences of dividing attention. In the first experiment, we compared the
      effects of one or two cues against an uncued baseline to determine the
      consequences of dividing attention in a paradigm with four rapid serial visual
      presentation (RSVP) streams. The results indicated that two simultaneous cues
      increase the accuracy of reporting two targets by almost the same amount as a
      single cue increases the report of a single target. These results suggest that
      when attention is divided between multiple locations, the attentional benefit at
      each location is not reduced in proportion to the total number of cues. A
      consequent prediction of this finding is that the identification of two RSVP
      targets should be better when they are presented simultaneously rather than
      sequentially. In a second experiment, we verified this prediction by finding
      evidence of lag-0 sparing: Two targets presented simultaneously in different
      locations were reported more easily than two targets separated by 100 ms. These
      findings argue against a biased-competition theory of attention. We suggest that
      visual attention, as triggered by a cue or target, is better described by a
      convergent gradient-field attention model.

PMID- 24728650
TI  - C(alpha) torsion angles as a flexible criterion to extract secrets from a
      molecular dynamics simulation.
AB  - Given the increasing complexity of simulated molecular systems, and the fact that
      simulation times have now reached milliseconds to seconds, immense amounts of
      data (in the gigabyte to terabyte range) are produced in current molecular
      dynamics simulations. Manual analysis of these data is a very time-consuming
      task, and important events that lead from one intermediate structure to another
      can become occluded in the noise resulting from random thermal fluctuations. To
      overcome these problems and facilitate a semi-automated data analysis, we
      introduce in this work a measure based on C(alpha) torsion angles: torsion angles
      formed by four consecutive C(alpha) atoms. This measure describes changes in the
      backbones of large systems on a residual length scale (i.e., a small number of
      residues at a time). Cluster analysis of individual C(alpha) torsion angles and
      its fuzzification led to continuous time patches representing (meta)stable
      conformations and to the identification of events acting as transitions between
      these conformations. The importance of a change in torsion angle to structural
      integrity is assessed by comparing this change to the average fluctuations in the
      same torsion angle over the complete simulation. Using this novel measure in
      combination with other measures such as the root mean square deviation (RMSD) and
      time series of distance measures, we performed an in-depth analysis of a
      simulation of the open form of DNA polymerase I. The times at which major
      conformational changes occur and the most important parts of the molecule and
      their interrelations were pinpointed in this analysis. The simultaneous
      determination of the time points and localizations of major events is a
      significant advantage of the new bottom-up approach presented here, as compared
      to many other (top-down) approaches in which only the similarity of the complete
      structure is analyzed. 

PMID- 24728651
TI  - Decreased allopregnanolone induced by hormonal contraceptives is associated with
      a reduction in social behavior and sexual motivation in female rats.
AB  - RATIONALE: Allopregnanolone is a neurosteroid involved in depression, memory,
      social, and sexual behavior. We have previously demonstrated that treatment with
      a combination of ethinylestradiol (EE) and levonorgestrel (LNG), two compounds
      frequently used in hormonal contraception, decreased brain allopregnanolone
      concentrations. These changes may contribute to some of the emotional and sexual
      disorders observed in hormonal contraceptive users. OBJECTIVES: We thus examined
      whether the reduction in allopregnanolone concentrations induced by long-term
      EE/LNG administration was associated with altered emotional, learning, social,
      and sexual behaviors. METHODS: Rats were orally treated with a combination of EE
      (0.030 mg) and LNG (0.125 mg) once a day for 4 weeks and were subjected to
      behavioral tests 24 h after the last administration. RESULTS: EE/LNG treatment
      reduced immobility behavior in the forced swim test, without affecting sucrose
      preference and spatial learning and memory. In the resident-intruder test, EE/LNG
      treated rats displayed a decrease in dominant behaviors associated with a
      reduction in social investigation. In the paced mating test, EE/LNG treated rats
      showed a reduction in proceptive behaviors, while the lordosis quotient was not
      affected. Progesterone, but not estradiol, administration to EE/LNG-treated rats
      increased sexual activity and cerebrocortical allopregnanolone concentrations.
      Prior administration of finasteride decreased allopregnanolone concentrations and
      abolished the increase in proceptivity induced by progesterone administration.
      CONCLUSIONS: The decrease in brain allopregnanolone concentrations induced by
      EE/LNG treatment is associated with a reduction in social behavior and sexual
      motivation in female rats. These results might be relevant to the side effects
      sometimes exhibited by women taking hormonal contraceptives.

PMID- 24728652
TI  - Developmental alterations in anxiety and cognitive behavior in serotonin
      transporter mutant mice.
AB  - RATIONALE: A promoter variant of the serotonin transporter (SERT) gene is known
      to affect emotional and cognitive regulation. In particular, the "short" allelic
      variant is implicated in the etiology of multiple neuropsychiatric disorders.
      Heterozygous (SERT(+/-)) and homozygous (SERT(-/-)) SERT mutant mice are valuable
      tools for understanding the mechanisms of altered SERT levels. Although these
      genetic effects are well investigated in adulthood, the developmental trajectory
      of altered SERT levels for behavior has not been investigated. OBJECTIVES: We
      assessed anxiety-like and cognitive behaviors in SERT mutant mice in early
      adolescence and adulthood to examine the developmental consequences of reduced
      SERT levels. Spine density of pyramidal neurons was also measured in
      corticolimbic brain regions. RESULTS: Adult SERT(-/-) mice exhibited increased
      anxiety-like behavior, but these differences were not observed in early
      adolescent SERT(-/-) mice. Conversely, SERT(+/-) and SERT(-/-) mice did display
      higher spontaneous alternation during early adolescence and adulthood. SERT(+/-)
      and SERT(-/-) also exhibited greater neuronal spine densities in the
      orbitofrontal but not the medial prefrontal cortices. Adult SERT(-/-) mice also
      showed an increased spine density in the basolateral amygdala. CONCLUSIONS:
      Developmental alterations of the serotonergic system caused by genetic
      inactivation of SERT can have different influences on anxiety-like and cognitive
      behaviors through early adolescence into adulthood, which may be associated with
      changes of spine density in the prefrontal cortex and amygdala. The altered
      maturation of serotonergic systems may lead to specific age-related
      vulnerabilities to psychopathologies that develop during adolescence.

PMID- 24728653
TI  - Decision-making impairment predicts 3-month hair-indexed cocaine relapse.
AB  - RATIONALE: One of the key outstanding challenges in cocaine dependence research
      is determining who is at risk of relapsing during treatment. OBJECTIVES: We
      examined whether cognitive decision-making profiles predict objectively (hair)
      indexed cocaine relapse at 3-month follow-up. METHODS: Thirty-three cocaine
      dependent patients commencing outpatient treatment in a public clinic performed
      baseline decision-making assessments with the original and variant versions of
      the Iowa Gambling Task, and provided a 3-cm hair sample 3 months afterwards.
      Based on Iowa Gambling Tasks' performance cut-offs, 5 patients had intact
      decision-making skills, 17 patients showed impaired sensitivity to reward or
      punishment (impairment in one of the tasks), and 9 patients showed insensitivity
      to future consequences (impairment in both tasks). Based on a 0.3 ng/mg cocaine
      cut-off, 23 patients were classified as relapsers and 10 as non-relapsers at the
      3-month follow-up. RESULTS: Eighty percent of patients with intact decision
      making were abstinent at follow-up, whereas 90% of patients with insensitivity to
      future consequences had relapsed. The two subgroups (relapsers and non-relapsers)
      showed no significant differences on drug use, comorbidities, or psychosocial
      function, and significantly differed on verbal but not performance IQ. A
      regression model including decision-making scores and verbal IQ predicted
      abstinence status with high sensitivity (95%) and moderately high specificity
      (81%). CONCLUSION: These preliminary findings demonstrate that decision-making
      profiles are associated with cocaine relapse. Moreover, combined decision-making
      and IQ assessments provide optimal predictive values over stimulant relapse,
      yielding significant opportunities for clinical translation.

PMID- 24728655
TI  - Social media as a source of information for patients with chronic obstructive
      pulmonary disease.

PMID- 24728656
TI  - Cardiac management of ventilator-assisted individuals with Duchenne muscular
      dystrophy.
AB  - As life expectancy of patients with Duchenne muscular dystrophy (DMD) has
      increased to the 5th decade, in part due to improved ventilatory support,
      cardiomyopathy is projected to increase as a cause of death. International
      guidelines recommend an annual assessment of cardiac function and initiation of
      appropriate pharmacological treatment. We conducted an audit of the cardiac
      management in patients with DMD requiring ventilatory support and reported a case
      series of the collated cardiac investigations. Patients with DMD requiring
      ventilatory support were included in the study. The date of the last
      electrocardiogram (ECG), echocardiogram (ECHO), cardiology review and
      pharmacological management were retrieved from the medical records. If an annual
      cardiac assessment had not been performed this was requested and the latest ECGs
      and ECHO reports were collated. A total of 30 patients with DMD (29 males, mean
      (SD) age of 30 (7) years) met the inclusion criteria. Although there was ECG and
      ECHO documentation in 24 and 21 individuals, respectively, it was only recent in
      10 and 6 individuals. In all, 60% of patients had been assessed by a
      cardiologist, but only 10% within the last year. Over half of the patients failed
      to attend their new appointments. From the available results, 18 of the 19
      patients had an abnormal ECG, 11 of the 16 patients had left ventricular (LV)
      impairment and 55% of patients had a change in prescription following cardiac
      investigations. There is a need for a coordinated cardiorespiratory approach
      towards adult patients with DMD. Over a third of patients had normal LV function
      suggesting that cardiomyopathy is not inevitable in this group. 

PMID- 24728654
TI  - TTD consensus document on the diagnosis and management of exocrine pancreatic
      cancer.
AB  - Exocrine pancreatic cancer (PC) is a very aggressive and heterogeneous tumor with
      several cellular signaling pathways implicated in its pathogenesis and
      maintenance. Several risk factors increase the risk of developing PC. Therapeutic
      strategies used are dictated by the extent of disease. Supportive treatment is
      critical because of the high frequency of symptoms. For localized disease,
      surgery followed by adjuvant gemcitabine is the standard. Neoadjuvant and new
      adjuvant chemotherapy regimens are being evaluated. Locally advanced disease
      should respond best guided by a multidisciplinary team. Various treatment options
      are appropriate such as chemotherapy alone or chemoradiotherapy with integration
      of rescue surgery if the tumor becomes resectable. In metastatic disease,
      chemotherapy should be reserved for patients with ECOG 0-1 using Folfirinox or
      gemcitabine plus nab-paclitaxel as the most recommended options. Several
      therapeutic strategies targeting unregulated pathways are under evaluation with
      an unmet need for biomarkers to guide management. 

PMID- 24728657
TI  - Geriatric rehabilitation for patients with advanced chronic obstructive pulmonary
      disease: a naturalistic prospective cohort study on feasibility and course of
      health status.
AB  - In view of the worldwide aging population, disease-specific geriatric
      rehabilitation (GR) programs are needed. Therefore, we developed and implemented
      a postacute GR program for patients with advanced chronic obstructive pulmonary
      disease (COPD) (the GR-COPD program). The aim of this study is to investigate the
      feasibility of the GR-COPD program and to present clinical data on patient
      characteristics and course of functional capacity and health status. This is a
      naturalistic prospective cohort study of patients with advanced COPD. A total of
      61 patients entered the GR-COPD program and were eligible to participate in this
      study. All patients suffered from advanced COPD, and comorbidities were frequent.
      On admission, functional capacity and health status were severely limited but
      showed significant and clinically relevant improvement during the GR-COPD
      program. Patients with advanced COPD admitted to hospital for an acute
      exacerbation suffer from severely impaired functional capacity and poor health
      status. Development and implementation of a postacute GR program for these
      patients are feasible and likely to offer substantial improvements. Further
      research is essential and should focus on designing a controlled intervention
      trial to investigate the efficacy of the program. 

PMID- 24728660
TI  - Spicing up the menu: evidence of fruit feeding in Galago moholi.
AB  - The African lesser bushbaby, Galago moholi, is described as a food specialist,
      feeding exclusively on small arthropods and gum primarily from Acacia karroo
      trees. We studied a population of G. moholi in a highly fragmented habitat in the
      southernmost part of its natural distributional range in South Africa. In this
      habitat, we opportunistically observed bushbabies feeding on fruits of the winter
      fruiting tree, Pappea capensis. Plot counts of tree composition revealed that
      although the dominant tree species in the area belonged to the genus Acacia, A.
      karroo trees were widely absent and gum could only be found in small quantities
      on other Acacia species. The analysis of P. capensis fruits showed high levels of
      protein, fat, and energy content, making the fruits a potentially important food
      source for G. moholi during winter when insect availability is low. Our
      observation is the first documented case of fruit feeding in G. moholi,
      suggesting that the species is not a food specialist as previously reported but
      can supplement its diet with fruit when available. 

PMID- 24728659
TI  - State-dependent inter-repeat contacts of exceptionally conserved asparagines in
      the inner helices of sodium and calcium channels.
AB  - Voltage-gated sodium and calcium channels play key roles in the physiology of
      excitable cells. The alpha-1 subunit of these channels folds from a polypeptide
      chain of four homologous repeats. In each repeat, the cytoplasmic halves of the
      pore-lining helices contain exceptionally conserved asparagines. Such
      conservation implies important roles, which are unknown. Mutations of the
      asparagines affect activation and inactivation gating as well as the action of
      pore-targeting ligands, including local anesthetics and steroidal agonists
      batrachotoxin and veratridine. In the absence of the open-channel structures,
      underlying mechanisms are unclear. Here, we modeled the pore module of Cav1.2 and
      Nav1.4 channels and their mutants in the open and closed states using the X-ray
      structures of potassium and sodium channels as templates. The energy of each
      model was Monte Carlo-minimized. The asparagines do not face the pore in the
      modeled states. In the open-channel models, the asparagine residue in a given
      repeat forms an inter-repeat H-bond with a polar residue, which is typically nine
      positions downstream from the conserved asparagine in the preceding repeat. The H
      bonds, which are strengthened by surrounding hydrophobic residues, would
      stabilize the open channel and shape the open-pore geometry. According to our
      calculation, the latter is much more sensitive to mutations of the asparagines
      than the closed-pore geometry. Rearrangement of inter-repeat contacts may explain
      effects of these mutations on the voltage dependence of activation and
      inactivation and action of pore-targeting ligands.

PMID- 24728661
TI  - DFT investigation of the vibrational properties of GC Watson-Crick and Hoogsteen
      base pairs in the presence of Mg2+, Ca2+, and Cu2+ ions.
AB  - The binding effects of Mg2+, Ca2+, and Cu2+ ions on the vibrational properties of
      guanine-cytosine base pairs have been performed using density functional theory
      investigations. Both Watson-Crick and Hoogsteen configurations of the base pairs
      were investigated. In Watson-Crick configuration, the metal was coordinated at N7
      atom of guanine, while in the case of Hoogsteen configuration, the coordination
      is at N3 atom of guanine. We have pointed out the geometric properties of the
      metal-GC base pairs structure, as well as the vibrational bands that can be used
      to detect the presence of metallic ions in the Watson-Crick and Hoogsteen GC
      structures. For the geometric models used by us, the vibrational amplitudes of
      metallic atoms were stronger for wavenumbers lower than 500 cm-1. This suggests
      that in the experimental studies on DNA the presence of the three metallic atoms
      (Mg, Ca, and Cu) can be explicitly detected at low frequencies.

PMID- 24728662
TI  - Undiagnosed vertebral fractures influence quality of life in postmenopausal women
      with reduced ultrasound parameters.
AB  - BACKGROUND: Osteoporosis, a multifactorial systemic skeletal disease
      characterized by low bone mass and microarchitectural deterioration of bone
      tissue leading to increased bone fragility, is a worldwide public health problem.
      Vertebral fractures affect approximately 20% of postmenopausal women and are a
      hallmark of osteoporosis, but they may pass unnoticed, although they may lead to
      long-term immobility and disability. QUESTIONS/PURPOSES: The aims of the present
      study were (1) to determine the prevalence and the severity of vertebral
      fractures in a large cohort of Italian women aged 60 years or older with reduced
      values of quantitative ultrasound parameters; and (2) to assess whether vertebral
      fractures and other variables may be associated with health-related quality of
      life. METHODS: A total of 2450 women without back pain aged 60 years or older,
      after the completion of the Quality of Life Questionnaire of the European
      Foundation for Osteoporosis QUALEFFO, underwent quantitative ultrasound
      evaluation of the calcaneus; in those with a stiffness t-score of <= -2 (n =
      1194), radiographic evaluation of the thoracic and lumbar spine was carried out
      and then quantitative morphometry was performed by dedicated software
      (MorphoXpress). The radiographic analysis was carried out on 885 women who
      presented films of adequate quality. Multivariate regression was used to adjust
      for confounding variables. RESULTS: Of those who underwent radiographic analysis,
      681 had no vertebral fractures, and 204 women (23.1%) had one or more previously
      undiagnosed vertebral fractures. The prevalence of previously undiagnosed
      vertebral fractures increased with advancing age with more than 30% of women
      older than 75 years having at least one fracture. Older age, body mass index, and
      severe vertebral fractures were independently associated with a worse total
      QUALEFFO score. CONCLUSIONS: We found that approximately one in four women showed
      evidence of undiagnosed vertebral fractures, and there was a strong age effect
      trend. Moreover, the severity grade of vertebral fractures, more than the number
      of fractures, was associated with a worsening of health-related quality of life
      as assessed by QUALEFFO. These findings confirm the clinical relevance of an
      early diagnosis of vertebral fractures and seem to support the usefulness of
      quantitative ultrasound measurements in the stratification of postmenopausal
      women at increased fracture risk. LEVEL OF EVIDENCE: Level III, prognostic study.
      See the Guidelines for Authors for a complete description of levels of evidence.

PMID- 24728663
TI  - Revision allograft reconstruction of the lateral collateral ligament complex in
      elbows with previous failed reconstruction and persistent posterolateral rotatory
      instability.
AB  - BACKGROUND: Primary reconstruction of the lateral collateral ligament complex
      (LCLC) using graft tissue restores elbow stability in many, but not all, elbows
      with acute or chronic posterolateral rotatory instability (PLRI). Revision
      reconstruction using a tendon allograft is occasionally considered for persistent
      PLRI, but the outcome of revision ligament reconstruction in this setting is
      largely unknown. QUESTIONS/PURPOSES: We determined whether revision allograft
      ligament reconstruction can (1) restore the stability and (2) result in improved
      elbow scores for patients with persistent PLRI of the elbow after a previous
      failed primary reconstructive attempt and in the context of the diverse pathology
      being addressed. METHODS: Between 2001 and 2011, 160 surgical elbow procedures
      were performed at our institution for the LCLC reconstruction using allograft
      tissue. Only patients undergoing revision allograft reconstruction of the LCLC
      for persistent PLRI with a previous failed primary reconstructive attempt using
      graft tissue and at least I year of followup were included in the study. Eleven
      patients (11 elbows) fulfilled our inclusion criteria and formed our study
      cohort. The cohort consisted of six female patients and five male patients. The
      mean age at the time of revision surgery was 36 years (range, 14-59 years). The
      revision allograft reconstruction was carried out after a mean of 3 years (range,
      2.5 months to 9 years) from a failed attempted reconstruction of the LCLC.
      Osseous deficiency to some extent was identified in the preoperative radiographs
      of eight elbows. Mean followup was 5 years (range, 1-12 years). RESULTS: Revision
      allograft reconstruction of the LCLC restored elbow stability in eight of the 11
      elbows; two of the three elbows with persistent instability were operated on a
      third time (at 6 and 7 months after allograft revision reconstruction). For
      elbows with no persistent instability, the mean Mayo Elbow Performance Score at
      most recent followup was 83 points (range, 60-100 points), and six elbows were
      rated with a good or excellent result. All patients with persistent instability
      had some degree of preoperative bone loss. CONCLUSIONS: Revision allograft
      reconstruction of the LCLC is an option for treating recurrent PLRI, although
      this is a complex and resistant problem, and nearly 1/2 of the patients in this
      cohort either had persistent instability and/or had a fair or poor elbow score.
      LEVEL OF EVIDENCE: Level IV, therapeutic study. See Instructions for Authors for
      a complete description of levels of evidence.

PMID- 24728664
TI  - Early response-based intensification of primary therapy in newly diagnosed
      multiple myeloma patients who are eligible for autologous stem cell
      transplantation: phase II study.
AB  - This phase II study prospectively evaluated the efficacy and tolerability of an
      early change in induction therapy before autologous stem cell transplantation
      (ASCT) in multiple myeloma (MM) patients who failed to achieve more than a
      partial response (PR) after two cycles of a cyclophosphamide, thalidomide, and
      dexamethasone (CTD) regimen. Patients aged 18-65 years received two cycles of CTD
      therapy, and then the patients who achieved more than a PR received two
      additional cycles of CTD therapy, while those who failed to achieve more than a
      PR were given intensified therapy with four cycles of a Vel-CD regimen
      (bortezomib, cyclophosphamide, and dexamethasone). After completing primary
      chemotherapy, the patients underwent ASCT. This study initially enrolled 64
      patients, although four were excluded. Of the patients, 60 were treated with CTD
      regimen and 8 patients also had the intensified Vel-CD regimen, of whom five
      showing improved responses. The overall response rate before ASCT in 59 patients
      was 94.9 %, including 27.1 % with a stringent complete response/complete
      response, 23.7 % with a very good partial response (VGPR), and 44.1 % with a PR.
      The median time to progression (TTP) was 33.2 months (95 % CI, 26.6-34.8).
      Patients who attained a VGPR or better after ASCT tended to have a longer TTP
      than the patients who did not (not reached vs. 24.2 months, P = 0.04). In
      conclusion, early response-adapted intensification with a Vel-CD regimen was a
      well-tolerated, effective strategy for improving the response before ASCT in
      patients with newly diagnosed MM. 

PMID- 24728666
TI  - Is principal component analysis an effective tool to predict face attractiveness?
      A contribution based on real 3D faces of highly selected attractive women,
      scanned with stereophotogrammetry.
AB  - In the literature, several papers report studies on mathematical models used to
      describe facial features and to predict female facial beauty based on 3D human
      face data. Many authors have proposed the principal component analysis (PCA)
      method that permits modeling of the entire human face using a limited number of
      parameters. In some cases, these models have been correlated with beauty
      classifications, obtaining good attractiveness predictability using wrapped 2D or
      3D models. To verify these results, in this paper, the authors conducted a three
      dimensional digitization study of 66 very attractive female subjects using a
      computerized noninvasive tool known as 3D digital photogrammetry. The sample
      consisted of the 64 contestants of the final phase of the Miss Italy 2010 beauty
      contest, plus the two highest ranked contestants in the 2009 competition. PCA was
      conducted on this real faces sample to verify if there is a correlation between
      ranking and the principal components of the face models. There was no correlation
      and therefore, this hypothesis is not confirmed for our sample. Considering that
      the results of the contest are not only solely a function of facial
      attractiveness, but undoubtedly are significantly impacted by it, the authors
      based on their experience and real faces conclude that PCA analysis is not a
      valid prediction tool for attractiveness. The database of the features belonging
      to the sample analyzed are downloadable online and further contributions are
      welcome. 

PMID- 24728667
TI  - The movement of a nerve in a magnetic field: application to MRI Lorentz effect
      imaging.
AB  - Direct detection of neural activity with MRI would be a breakthrough innovation
      in brain imaging. A Lorentz force method has been proposed to image nerve
      activity using MRI; a force between the action currents and the static MRI
      magnetic field causes the nerve to move. In the presence of a magnetic field
      gradient, this will cause the spins to precess at a different frequency,
      affecting the MRI signal. Previous mathematical modeling suggests that this
      effect is too small to explain the experimental data, but that model was limited
      because the action currents were assumed to be independent of position along the
      nerve and because the magnetic field was assumed to be perpendicular to the
      nerve. In this paper, we calculate the nerve displacement analytically without
      these two assumptions. Using realistic parameter values, the nerve motion is <5
      nm, which induced a phase shift in the MRI signal of <0.02 degrees . Therefore,
      our results suggest that Lorentz force imaging is beyond the capabilities of
      current technology. 

PMID- 24728665
TI  - Peretinoin after curative therapy of hepatitis C-related hepatocellular
      carcinoma: a randomized double-blind placebo-controlled study.
AB  - BACKGROUND: Effective prophylactic therapies have not been established for
      hepatocellular carcinoma recurrence. Peretinoin represents one novel option for
      patients with hepatitis C virus-related hepatocellular carcinoma (HCV-HCC), and
      it was tested in a multicenter, randomized, double-blind, placebo-controlled
      study. METHODS: Patients with curative therapy were assigned to one of the
      following regimens: peretinoin 600, 300 mg/day, or placebo for up to 96 weeks.
      The primary outcome was recurrence-free survival (RFS). RESULTS: Of the 401
      patients initially enrolled, 377 patients were analyzed for efficacy. The RFS
      rates in the 600-mg group, the 300-mg group, and the placebo group were 71.9,
      63.6, and 66.0 % at 1 year, and 43.7, 24.9, and 29.3 % at 3 years, respectively.
      The primary comparison of peretinoin (300 and 600-mg) with placebo was not
      significant (P = 0.434). The dose-response relationship based on the hypothesis
      that "efficacy begins to increase at 600 mg/day" was significant (P = 0.023,
      multiplicity-adjusted P = 0.048). The hazard ratios for RFS in the 600-mg group
      vs. the placebo group were 0.73 [95 % confidence interval (CI) 0.51-1.03] for the
      entire study period and 0.27 (95 % CI 0.07-0.96) after 2 years of the
      randomization. Common adverse events included ascites, increased blood pressure,
      headache, presence of urine albumin, and increased transaminases. CONCLUSIONS:
      Although the superiority of peretinoin to placebo could not be validated, 600
      mg/day was shown to be the optimal dose, and treatment may possibly reduce the
      recurrence of HCV-HCC, particularly after 2 years. The efficacy and safety of
      peretinoin 600 mg/day should continue to be evaluated in further studies.

PMID- 24728669
TI  - Associations of daily walking and television viewing time with liver cancer
      mortality: findings from the Japan Collaborative Cohort Study.
AB  - BACKGROUND AND PURPOSE: Several studies have suggested that daily vigorous
      physical activity reduces the risk of liver cancer, whereas sedentary behavior
      increases the risk of several cancers. However, the link between liver cancer and
      low-intensity physical activity (walking) and sedentary behavior is unclear.
      Therefore, we explored the links between liver cancer mortality and daily walking
      time/television (TV) viewing time in Japanese adults aged 40-79 years in a large
      scale nationwide cohort study. METHODS: We excluded participants with a history
      of liver disease, cancer, stroke, or myocardial infarction at baseline (1988
      1990) and those who died within the first 5 years of follow-up. A total of 69,752
      adults (28,642 men and 41,110 women) were enrolled and followed for a median of
      19.4 years. The Cox proportional hazards model was used to calculate hazard
      ratios (HRs) and 95% confidence intervals (CI) for liver cancer mortality
      adjusted for age, sex, and other possible confounding factors. RESULTS: During
      the study period, 267 participants died of liver cancer. The HRs of participants
      who walked for >0.5 h/day and watched TV for 2-4 versus <2 h/day were 0.58 (95%
      CI 0.39-0.89) and 0.58 (95% CI 0.35-0.98), respectively, compared with those who
      walked for <0.5 h/day and watched TV for >4 h/day. CONCLUSIONS: Our findings
      suggest that longer walking times and shorter TV viewing times may reduce the
      risk of liver cancer.

PMID- 24728670
TI  - Occupational exposure and ovarian cancer risk.
AB  - PURPOSE: Relatively little work has been done concerning occupational risk
      factors in ovarian cancer. Although studies conducted in occupational settings
      have reported positive associations, their usefulness is generally limited by the
      lack of information on important confounders. In a population-based case-control
      study, we assessed risk for developing epithelial ovarian cancer (EOC) associated
      with occupational exposure while accounting for important confounders. METHODS:
      Participants were identified through provincial population-based registries.
      Lifetime occupational history and information on potential confounding factors
      were obtained through a self-administered questionnaire. Unconditional logistic
      regression and the likelihood ratio test were used to assess EOC risk with each
      occupation (or industry), relative to all other occupations (or industries),
      adjusting for potential confounders including body mass index, oral contraceptive
      use, menopausal hormone therapy, parity, age at first childbirth, age at
      menarche, age at menopause, family history of breast and ovarian cancer in mother
      and sister(s), tubal ligation, partial oophorectomy, and hysterectomy.
      Occupations and industries were coded according to the Canadian Standard
      Occupational Classification (SOC) and Standard Industrial Classification (SIC).
      RESULTS: Significant excess risk was observed for several groups of teaching
      occupations, including SOC 27, teaching and related (adjusted OR 1.77, 95% CI
      1.15-2.81) and SOC 279, other teaching and related (adjusted OR 3.11, 95% CI 1.35
      8.49). Significant excess was also seen for a four-digit occupational group SOC
      4131, bookkeepers and accounting clerks (adjusted OR 2.80, 95% CI 1.30-6.80).
      Industrial sub-groups showing significant excess risk included SIC 65, other
      retail stores (adjusted OR 2.19, 95 % CI 1.16-4.38); SIC 85, educational service
      (adjusted OR 1.45, 95% CI 1.00-2.13); and SIC 863, non-institutional health
      services (adjusted OR 2.54, 95% CI 1.13-6.52). CONCLUSIONS: Our study found an
      elevated EOC risk for teaching occupations and is the first study to observe such
      an increased risk after adjustment for potential confounders. Further studies
      with more detailed assessment of the work environment and unique lifestyle
      characteristics may be fruitful in elucidating this etiology.

PMID- 24728678
TI  - Central fatigue contributes to the greater reductions in explosive than maximal
      strength with high-intensity fatigue.
AB  - The study aimed to assess the influence of fatigue induced by repeated high-force
      explosive contractions on explosive and maximal isometric strength of the human
      knee extensors and to examine the neural and contractile mechanisms for the
      expected decrement. Eleven healthy untrained males completed 10 sets of voluntary
      maximal explosive contractions (five times 3 s, interspersed with 2 s rest). Sets
      were separated by 5 s, during which supramaximal twitch and octet contractions
      [eight pulses at 300 Hz that elicit the contractile peak rate of force
      development (pRFD)] were evoked. Explosive force, at specific time points, and
      pRFD were assessed for voluntary and evoked efforts, expressed in absolute terms
      and normalized to maximal/peak force. Maximal voluntary contraction force (MVCF)
      and peak evoked forces were also determined. Surface EMG amplitude was measured
      from three superficial agonists and normalized to maximal compound action
      potential area. By set 10, explosive force (47-52%, P < 0.001) and MVCF (42%, P <
      0.001) had declined markedly. Explosive force declined more rapidly than MVCF,
      with lower normalized explosive force at 50 ms (29%, P = 0.038) that resulted in
      reduced normalized explosive force from 0 to 150 ms (11-29%, P <= 0.038). Neural
      efficacy declined by 34%, whilst there was a 15-28% reduction in quadriceps EMG
      amplitude during voluntary efforts (all P <= 0.03). There was demonstrable
      contractile fatigue (pRFD: octet, 27%; twitch, 66%; both P < 0.001). Fatigue
      reduced normalized pRFD for the twitch (21%, P = 0.001) but not the octet (P =
      0.803). Fatigue exerted a more rapid and pronounced effect on explosive force
      than on MVCF, particularly during the initial 50 ms of contraction, which may
      explain the greater incidence of injuries associated with fatigue. Both neural
      and contractile fatigue mechanisms appeared to contribute to impaired explosive
      voluntary performance. 

PMID- 24728679
TI  - Intrinsic properties of rostral ventrolateral medulla presympathetic and
      bulbospinal respiratory neurons of juvenile rats are not affected by chronic
      intermittent hypoxia.
AB  - The presympathetic neurons in the rostral ventrolateral medulla (RVLM) are
      considered to be the source of the sympathetic activity, and there is
      experimental evidence that these cells present intrinsic autodepolarization.
      There is also evidence that an important respiratory neuronal population located
      in the RVLM/Botzinger complex (BotC) corresponds to augmenting expiratory neurons
      (aug-E), which send projections to the phrenic nucleus in the spinal cord.
      However, the pacemaker activity of presympathetic neurons and the intrinsic
      properties of aug-E neurons had not been evaluated in brainstem slices of
      juvenile rats (postnatal day 35). Chronic intermittent hypoxia (CIH) is a
      sympathetic-mediated hypertension model, which seems to produce an associated
      increase in the activity of aug-E neurons. In this study, we evaluated the
      effects of CIH on the intrinsic properties of RVLM/BotC presympathetic and
      phrenic nucleus-projecting neurons (aug-E) in brainstem slices of juvenile rats
      (postnatal day 35). We observed that all presympathetic neurons presented
      spontaneous action potential firing (n = 18), which was not abolished by
      ionotropic receptor antagonism. In addition, exposure to 10 days of CIH produced
      no changes in their intrinsic passive properties, firing pattern or excitability.
      Most aug-E neurons presented spontaneous firing in control conditions (13 of 15
      neurons), and this characteristic was preserved after blocking fast synaptic
      transmission (12 of 15 neurons), clearly demonstrating their intrinsic pacemaker
      activity. Chronic intermittent hypoxia also produced no changes in intrinsic
      passive properties, frequency and pattern of discharge or excitability of the aug
      E neurons. The present study shows that: (i) it is possible to record the
      electrophysiological properties of RVLM/BotC presympathetic and aug-E neurons in
      brainstem slices from juvenile rats; (ii) these neurons present characteristics
      of intrinsic pacemakers; and (iii) their intrinsic properties were not altered by
      chronic intermittent hypoxia. 

PMID- 24728680
TI  - Exercise performance is regulated during repeated sprints to limit the
      development of peripheral fatigue beyond a critical threshold.
AB  - We hypothesized that exercise performance is adjusted during repeated sprints in
      order not to surpass a critical threshold of peripheral fatigue. Twelve men
      randomly performed three experimental sessions on different days, i.e. one single
      10 s all-out sprint and two trials of 10 * 10 s all-out sprints with 30 s of
      passive recovery in between. One trial was performed in the unfatigued state
      (CTRL) and one following electrically induced quadriceps muscle fatigue (FTNMES).
      Peripheral fatigue was quantified by comparing pre- with postexercise changes in
      potentiated quadriceps twitch force (DeltaQtw-pot) evoked by supramaximal
      magnetic stimulation of the femoral nerve. Central fatigue was estimated by
      comparing pre- with postexercise voluntary activation of quadriceps motor units.
      The root mean square (RMS) of the vastus lateralis and vastus medialis EMG
      normalized to maximal M-wave amplitude (RMS.Mmax (-1)) was also calculated during
      sprints. Compared with CTRL condition, pre-existing quadriceps muscle fatigue in
      FTNMES (DeltaQtw-pot = -29 +/- 4%) resulted in a significant (P < 0.05) reduction
      in power output (-4.0 +/- 0.9%) associated with a reduction in RMS.Mmax (-1).
      However, DeltaQtw-pot postsprints decreased by 51% in both conditions, indicating
      that the level of peripheral fatigue was identical and independent of the degree
      of pre-existing fatigue. Our findings show that power output and cycling EMG are
      adjusted during exercise in order to limit the development of peripheral fatigue
      beyond a constant threshold. We hypothesize that the contribution of peripheral
      fatigue to exercise limitation involves a reduction in central motor drive in
      addition to the impairment in muscular function. 

PMID- 24728700
TI  - Predictors of stress among parents in pediatric intensive care unit: a
      prospective observational study.
AB  - OBJECTIVE: To determine the sociodemographic and clinical factors leading to
      stress among parents whose children are admitted in pediatric intensive care unit
      (PICU). METHODS: A prospective observational study was conducted in PICU of a
      tertiary care hospital of north India. Parents of children admitted to PICU for
      at least 48 h duration were eligible for participation. At the end of 48 h,
      parental stress was assessed using parental stress scale (PSS:PICU) questionnaire
      which was administered to the parents. Baseline demographic and clinical
      parameters of children admitted to PICU were recorded. The parental stress was
      compared with demographic and clinical characteristics of children using
      appropriate statistical methods. RESULTS: A total of 49 parents were finally
      eligible for participation. Mean (SD) parental stress scores was highest in
      domains of procedures [1.52 (0.66)] and behavior and emotional [1.32 (0.42)]
      subscales. Mean (SD) total parental stress score among intubated children [1.31
      (0.25)] was significantly more than among non intubated children [0.97 (0.26)] (p
      < 0.001). However, parental stress score were comparable in terms of gender (p =
      0.15) and socioeconomic status (p = 0.32). On subscale analysis, it was found
      that professional communication is a significant stressor in age groups 0-12 mo
      [0.61(0.41)] (p = 0.02). It was observed that parents of intubated children were
      significantly stressed by the physical appearance of their children (p < 0.001),
      procedures performed on them (p = 0.008) and impairment in parental role (p =
      0.002). Total parental stress score had a positive correlation with PRISM score
      (r = 0.308). CONCLUSIONS: Indian parents are stressed maximally with environment
      of PICU. Factor leading to parental stress was intubation status of the child and
      was not affected by gender or socio demographic profile of the parents.

PMID- 24728702
TI  - Intrapericardial immature teratoma with successful treatment in a neonate.
AB  - Intra-pericardial teratoma, most often a benign tumor, is an extremely rare
      condition in a newborn. It can be a diagnostic and therapeutic challenge if it
      presents with massive pericardial effusion. Complete surgical excision of the
      tumor is necessary because of its association with tissues of malignant
      potential. A 16-d-old newborn was diagnosed with intra pericardial immature
      teratoma (IT) and managed successfully with multidisciplinary team approach by
      prompt referral for complete surgical resection followed by adjuvant chemotherapy
      with carboplatin, etoposide and bleomycin (JEB) to prevent recurrence. The infant
      is now on close follow up with monitoring of serum alpha fetoprotein (AFP) levels
      and imaging studies for early diagnosis of recurrence of tumor and chemotherapy
      related complications. 

PMID- 24728701
TI  - Hemophagocytic lymphohistiocytosis syndrome in Dengue hemorrhagic fever.
AB  - Hemophagocytic lymphohistiocytosis (HLH) is a life threatening florid activation
      of macrophages of the lymphoreticular system. It is reported to be associated
      with dengue in children in India and carries a high mortality. Patients present
      with high fever, worsening blood cell counts, splenomegaly, abnormal liver
      enzymes with features of liver failure, coagulopathy and neurological
      complications. The diagnosis is according to "Diagnostic Guidelines for HLH
      2004", based on a triad of clinical, blood parameters and bone marrow cytology.
      In the present study, data of 212 children admitted with dengue were analyzed. Of
      212 children, 31 children were classified as suspect HLH and advised bone marrow
      evaluation; of whom 23 children had marrow evidence of HLH. Worsening of blood
      cell counts were recorded in all children with a mean platelet count of 58,303.03
      cells/cumm, low hematocrit in 95.65 %, low mean hemoglobin level of 8.37 g/dL,
      high erythrocyte sedimentation rate (ESR) and prolonged pro-thrombin
      time/international normalization ratio (PT/INR). Serum triglycerides, ferritin
      and transaminases were high. Of the 23 children, 19 patients received intravenous
      immunoglobulin (IVIG) and all of these children recovered. Dengue with multi
      organ dysfunction is commonly concurrent to HLH in the marrow and hence, an early
      diagnosis based on clinical, laboratory and bone marrow evaluation is
      significant. A bone marrow evaluation confirms the diagnosis of HLH. 

PMID- 24728703
TI  - Mumps infection associated with intravascular hemolysis, acute renal failure and
      pancreatitis.

PMID- 24728705
TI  - Coronary vasospasm causing acute myocardial infarction: an unusual result of wild
      mushroom poisoning.

PMID- 24728704
TI  - Defined morphological criteria allow reliable diagnosis of colorectal serrated
      polyps and predict polyp genetics.
AB  - Criteria for the diagnosis of serrated colorectal lesions (hyperplastic polyp,
      sessile serrated adenoma without or with dysplasia--which we called mixed polyp-
      and traditional serrated adenoma) for which consensus has been reached should be
      validated for applicability in daily practice in terms of inter-observer
      reproducibility and their association with clinical features and (epi)genetic
      events. A study set was created from a consecutive series of colorectal polyps (n
      = 1,926) by selecting all sessile serrated adenomas, traditional serrated
      adenomas and mixed polyps. We added consecutive series of hyperplastic polyps,
      classical adenomas and normal mucosa samples for a total of 200 specimens. With
      this series, we conducted an inter-observer study, encompassing ten pathologists
      with gastrointestinal pathology experience from five European countries, in three
      rounds in which all cases were microscopically evaluated. An assessment of single
      morphological criteria was included, and these were correlated with clinical
      parameters and the mutation status of KRAS, BRAF and PIK3CA and the methylation
      status of MLH1. Gender, age and localisation were significantly associated with
      certain types of lesions. Kappa statistics revealed moderate to good inter
      observer agreement for polyp classification (kappa = 0.56 to 0.63), but for
      single criteria, this varied considerably (kappa = 0.06 to 0.82). BRAF mutations
      were frequently found in hyperplastic polyps (86 %, 62/72) and sessile serrated
      adenomas (80 %, 41/51). KRAS mutations occurred more frequently in traditional
      serrated adenomas (78 %, 7/9) and less so in classical adenomas (20 %, 10/51).
      Single morphological criteria for sessile serrated adenomas showed significant
      correlation with BRAF mutation (all p <= 0.001), and those for classical adenomas
      or traditional serrated adenoma correlated significantly with KRAS mutation (all
      p < 0.001). Therefore, single well-defined morphological criteria are predictive
      for genetic alterations in colorectal polyps.

PMID- 24728706
TI  - Elevated pulmonary artery pressure predicts poor outcome after cardiac
      resynchronization therapy.
AB  - PURPOSE: Pulmonary artery hypertension is correlated with poor clinical prognosis
      in patients with chronic heart failure. However, there is a paucity of data
      concerning the impact of baseline pulmonary artery systolic pressure (PASP) on
      clinical outcome after cardiac resynchronization therapy (CRT). The aim of the
      study is to evaluate the association of baseline PASP with CRT response. METHODS:
      One hundred eighty-seven consecutive patients undergoing CRT were screened for
      retrospective analysis. Patients were stratified into three groups based on
      preoperative PASP which was determined by echocardiogram (group I, PASP < 45
      mmHg; group II, 45 mmHg <= PASP < 70 mmHg; and group III, PASP >= 70 mmHg).
      Clinical and echocardiographic improvements, as well as the response rate, were
      assessed 6 months after CRT. Long-term prognosis, measured as transplantation-
      and hospitalization-free survival, was also compared across the three groups.
      RESULTS: One hundred eighty-three patients were evaluated with a mean age of 60.7
      +/- 11.2 years. At 6-month follow-up, patients in group I demonstrated greater
      clinical improvements (p < 0.05) and higher response rate (p < 0.01) than groups
      II and III. Compared with group I, death or transplantation was significantly
      more often noted in group II (hazard ratio, 4.89; 95% CI, 1.53-15.60; p = 0.007)
      and group III (hazard ratio, 5.91; 95% CI, 1.25-27.94; p = 0.025) as was heart
      failure readmission for group II (hazard ratio, 2.48; 95% CI, 1.24-4.98; p =
      0.011) and group III (hazard ratio, 6.39; 95% CI, 2.26-18.06; p < 0.001).
      CONCLUSIONS: Patients with elevated PASP derive less benefit from CRT. Baseline
      PASP could serve as an independent predictor for long-term prognosis.

PMID- 24728707
TI  - Characteristics of invasive aspergillosis in neutropenic haematology patients
      (Sousse, Tunisia).
AB  - Although scarce, available data suggest that the epidemiology of invasive
      aspergillosis (IA) in North Africa differs from northern countries, where more
      than 80 % is caused by Aspergillus fumigatus. This study aimed at describing the
      epidemiology of IA in the region of Sousse, Tunisia, and at assessing the
      usefulness of the available diagnostic tools. For 2 years, clinical and
      mycological data were prospectively collected from 175 neutropenia episodes of 91
      patients hospitalised in the haematology department at the Farhat Hached hospital
      in Sousse (Tunisia). Screening for galactomannan antigen was positive in 40 % of
      neutropenia episodes; Aspergillus PCR was positive in 42 % of the tested sera.
      Nine patients were classified as probable and two as possible IA according to the
      EORTC/MSG criteria. Twelve patients who prematurely died, had no CT scan and
      could not be classified. Fifty-six Aspergillus spp. were isolated in 53 (6.5 %)
      sputa collected from 35 (20 %) patients. The following species were identified
      with MALDI-TOF mass spectrometry and DNA sequencing: A. niger, 35 %; A. flavus,
      38 %; A. tubingensis, 19 %; A. fumigatus, 4 %; A. westerdijkiae, 2 % and A.
      ochraceus, 2 %. Our findings highlight the epidemiological features of IA in
      Tunisia, which is characterised by the predominance of Aspergillus spp. from
      sections Nigri and Flavi.

PMID- 24728708
TI  - Testing the economic independence hypothesis: the effect of an exogenous increase
      in child support on subsequent marriage and cohabitation.
AB  - We examine the effects of an increase in income on the cohabitation and marriage
      of single mothers. Using data from an experiment that resulted in randomly
      assigned differences in child support receipt for welfare-receiving single
      mothers, we find that exogenous income increases (as a result of receiving all
      child support that was paid) are associated with significantly lower cohabitation
      rates between mothers and men who are not the fathers of their child(ren).
      Overall, these results support the hypothesis that additional income increases
      disadvantaged women's economic independence by reducing the need to be in the
      least stable type of partnerships. Our results also show the potential importance
      of distinguishing between biological and social fathers. 

PMID- 24728709
TI  - The Biosynthetic Pathway of Indole-3-Carbaldehyde and Indole-3-Carboxylic Acid
      Derivatives in Arabidopsis.
AB  - Indolic secondary metabolites play an important role in pathogen defense in
      cruciferous plants. In Arabidopsis (Arabidopsis thaliana), in addition to the
      characteristic phytoalexin camalexin, derivatives of indole-3-carbaldehyde (ICHO)
      and indole-3-carboxylic acid (ICOOH) are synthesized from tryptophan via the
      intermediates indole-3-acetaldoxime and indole-3-acetonitrile. Based on feeding
      experiments combined with nontargeted metabolite profiling, their composition in
      nontreated and silver nitrate (AgNO3)-treated leaf tissue was comprehensively
      analyzed. As major derivatives, glucose conjugates of 5-hydroxyindole-3
      carbaldehyde, ICOOH, and 6-hydroxyindole-3-carboxylic acid were identified.
      Quantification of ICHO and ICOOH derivative pools after glucosidase treatment
      revealed that, in response to AgNO3 treatment, their total accumulation level was
      similar to that of camalexin. ARABIDOPSIS ALDEHYDE OXIDASE1 (AAO1), initially
      discussed to be involved in the biosynthesis of indole-3-acetic acid, and
      Cytochrome P450 (CYP) 71B6 were found to be transcriptionally coexpressed with
      camalexin biosynthetic genes. CYP71B6 was expressed in Saccharomyces cerevisiae
      and shown to efficiently convert indole-3-acetonitrile into ICHO and ICOOH,
      thereby releasing cyanide. To evaluate the role of both enzymes in the
      biosynthesis of ICHO and ICOOH derivatives, knockout and overexpression lines for
      CYP71B6 and AAO1 were established and analyzed for indolic metabolites. The
      observed metabolic phenotypes suggest that AAO1 functions in the oxidation of
      ICHO to ICOOH in both nontreated and AgNO3-treated leaves, whereas CYP71B6 is
      relevant for ICOOH derivative biosynthesis specifically after induction. In
      summary, a model for the biosynthesis of ICHO and ICOOH derivatives is presented.

PMID- 24728710
TI  - Mutational analysis of the helicase domain of a replication initiator protein
      reveals critical roles of Lys 272 of the B' motif and Lys 289 of the beta-hairpin
      loop in geminivirus replication.
AB  - Replication initiator protein (Rep) is indispensable for rolling-circle
      replication of geminiviruses, a group of plant-infecting circular ssDNA viruses.
      However, the mechanism of DNA unwinding by circular ssDNA virus-encoded helicases
      is unknown. To understand geminivirus Rep function, we compared the sequence and
      secondary structure of Rep with those of bovine papillomavirus E1 and employed
      charged residue-to-alanine scanning mutagenesis to generate a set of single
      substitution mutants in Walker A (K227), in Walker B (D261, 262), and within or
      adjacent to the B' motif (K272, K286 and K289). All mutants were asymptomatic and
      viral accumulation could not be detected by Southern blotting in both tomato and
      N. benthamiana plants. Furthermore, the K272 and K289 mutants were deficient in
      DNA binding and unwinding. Biochemical studies and modelling data based on
      comparisons with the known structures of SF3 helicases suggest that the conserved
      lysine (K289) located in a predicted beta-hairpin loop may interact with ssDNA,
      while lysine 272 in the B' motif (K272) located on the outer surface of the
      protein is presumably involved in coupling ATP-induced conformational changes to
      DNA binding. To the best of our knowledge, this is the first time that the roles
      of the B' motif and the adjacent beta-hairpin loop in geminivirus replication
      have been elucidated. 

PMID- 24728711
TI  - Genetic diversity of feline morbilliviruses isolated in Japan.
AB  - Feline morbillivirus (FmoPV) is an emerging virus in domestic cats and considered
      to be associated with tubulointerstitial nephritis. Although FmoPV was first
      described in China in 2012, there has been no report of the isolation of this
      virus in other countries. In this report, we describe the isolation and
      characterization of FmoPV from domestic cats in Japan. By using reverse
      transcription (RT)-PCR, we found that three of 13 urine samples from cats brought
      to veterinary hospitals were positive for FmoPV. FmoPV strains SS1 to SS3 were
      isolated from the RT-PCR-positive urine samples. Crandell-Rees feline kidney
      (CRFK) cells exposed to FmoPV showed cytopathic effects with syncytia formation,
      and FmoPV N protein was detected by indirect immunofluorescence assays. In
      addition, pleomorphic virus particles with apparent glycoprotein envelope spikes
      were observed by electron microscopy. By sequence analysis of FmoPV H and L
      genes, we found that FmoPVs showed genetic diversity; however, signatures of
      positive selection were not identified. 

PMID- 24728712
TI  - A novel approach to propagate flavivirus infectious cDNA clones in bacteria by
      introducing tandem repeat sequences upstream of virus genome.
AB  - Despite tremendous efforts to improve the methodology for constructing flavivirus
      infectious cDNAs, the manipulation of flavivirus cDNAs remains a difficult task
      in bacteria. Here, we successfully propagated DNA-launched type 2 dengue virus
      (DENV2) and Japanese encephalitis virus (JEV) infectious cDNAs by introducing
      seven repeats of the tetracycline-response element (7*TRE) and a minimal
      cytomegalovirus (CMVmin) promoter upstream of the viral genome. Insertion of the
      7*TRE-CMVmin sequence upstream of the DENV2 or JEV genome decreased the cryptic
      E. coli promoter (ECP) activity of the viral genome in bacteria, as measured
      using fusion constructs containing DENV2 or JEV segments and the reporter gene
      Renilla luciferase in an empty vector. The growth kinetics of recombinant viruses
      derived from DNA-launched DENV2 and JEV infectious cDNAs were similar to those of
      parental viruses. Similarly, RNA-launched DENV2 infectious cDNAs were generated
      by inserting 7*TRE-CMVmin, five repeats of the GAL4 upstream activating sequence,
      or five repeats of BamHI linkers upstream of the DENV2 genome. All three tandem
      repeat sequences decreased the ECP activity of the DENV2 genome in bacteria.
      Notably, 7*TRE-CMVmin stabilized RNA-launched JEV infectious cDNAs and reduced
      the ECP activity of the JEV genome in bacteria. The growth kinetics of
      recombinant viruses derived from RNA-launched DENV2 and JEV infectious cDNAs
      displayed patterns similar to those of the parental viruses. These results
      support a novel methodology for constructing flavivirus infectious cDNAs, which
      will facilitate research in virology, viral pathogenesis and vaccine development
      of flaviviruses and other RNA viruses. 

PMID- 24728713
TI  - Growth of osteosarcoma cells in a three-dimensional bone-like matrix alters their
      susceptibility to adeno-associated virus.
AB  - Osteosarcoma cells U2OS are partially susceptible to adeno-associated virus (AAV)
      2 infection, allowing efficient synthesis of Rep proteins and, in a low
      percentage of cells, capsid production. It is not clear if this partial
      susceptibility to infection is due to the bone-cell-like nature of these cells or
      is a result of their transformed properties. Here, we grew osteosarcoma cells in
      a biomimetic three-dimensional bone-like matrix composed of calcium phosphate and
      chitosan, and tested whether this would increase or reduce their permissiveness
      to virus. The osteosarcoma cells grew in the matrix and began to express the
      alkaline phosphatase bone cell differentiation marker. This was accompanied by a
      block to their infection by AAV, as indicated by Rep and capsid production.
      Infection of cells growing in three-dimensional tissue-like matrices could be, in
      a wider context, a practical way to mimic in vivo conditions. 

PMID- 24728714
TI  - Structural and functional studies on a thermostable polyethylene terephthalate
      degrading hydrolase from Thermobifida fusca.
AB  - Bacterial cutinases are promising catalysts for the modification and degradation
      of the widely used plastic polyethylene terephthalate (PET). The improvement of
      the enzyme for industrial purposes is limited due to the lack of structural
      information for cutinases of bacterial origin. We have crystallized and
      structurally characterized a cutinase from Thermobifida fusca KW3 (TfCut2) in
      free as well as in inhibitor-bound form. Together with our analysis of the
      thermal stability and modelling studies, we suggest possible reasons for the
      outstanding thermostability in comparison to the less thermostable homolog from
      Thermobifida alba AHK119 and propose a model for the binding of the enzyme
      towards its polymeric substrate. The TfCut2 structure is the basis for the
      rational design of catalytically more efficient enzyme variants for the
      hydrolysis of PET and other synthetic polyesters. 

PMID- 24728715
TI  - Construction of a constitutively expressed homo-fermentative pathway in
      Lactobacillus brevis.
AB  - Lactobacillus brevis is a promising lactic acid producing strain that
      simultaneously utilizes glucose and xylose from lignocellulosic hydrolysate
      without carbon catabolic repression and inhibition. The production of by-products
      acetic acid and ethanol has been the major drawback of this strain. Two genes,
      pfkA (fructose-6-phosphate kinase [PFK]) and fbaA (fructose-1,6-biphosphate
      aldolase [FBA]), that encode the key enzymes of the EMP/glycolytic pathway from
      Lactobacillus rhamnosus, were fused to the downstream of the strong promoter P32
      and expressed in L. brevis s3f4 as a strategy to minimize the formation of by
      products. By expressing the two enzymes, a homo-fermentative pathway for lactic
      acid production was constructed. The lactic acid yields achieved from glucose in
      the transformants were 1.12 and 1.16 mol/mol, which is higher than that of the
      native strain (0.74 mol/mol). However, the lactic acid yield from xylose in the
      transformants stayed the same as that of the native strain. Enzyme assay
      indicated that the activity of the foreign protein FBA in the transformants was
      much higher than that of the native strains, but was ten times lower than that in
      L. rhamnosus. This result was consistent with the metabolic flux analysis, which
      indicated that the conversion efficiency of the expressed PFK and FBA was
      somewhat low. Less than 20 % of the carbons accumulated in the form of fructose-6
      phosphate were converted into glyceraldehyde-3-phosphate (GAP) by the expressed
      PFK and FBA. Metabolic flux analysis also indicated that the enzyme
      phosphoketolase (XPK) played an important role in splitting the carbon flow from
      the pentose phosphate pathway to the phosphoketolase pathway. This study
      suggested that the lactic acid yield of L. brevis could be improved by
      constructing a homo-fermentative pathway.

PMID- 24728716
TI  - Treatment of metabolic syndrome with ankaflavin, a secondary metabolite isolated
      from the edible fungus Monascus spp.
AB  - Edible fungi of the Monascus species have been used as traditional Chinese
      medicine in eastern Asia for several centuries. Monascus-fermented products
      possess a number of functional secondary metabolites, including anti-inflammatory
      pigments (such as monascin and ankaflavin [AK]), monacolins, and dimerumic acid.
      These secondary metabolites have anti-inflammatory, anti-oxidative, and anti
      tumor activities. We found that AK positively regulates several transcription
      factors associated with the prevention of metabolic syndrome and other diseases,
      including peroxisome proliferator-activated receptor (PPAR)-gamma, PPAR-alpha,
      and nuclear factor (erythroid-derived 2)-like 2 (Nrf2). AK reduced hyperglycemia
      and enhanced pancreatic function via PPAR-gamma activation and increased lipid
      metabolism due to PPAR-alpha activation. The compound also exerted antioxidant
      effects via activation of Nrf2. These results suggest that AK belongs to the
      class of selective peroxisome proliferator-activated receptor modulators
      (SPPARMs), which are associated with a good safety profile when used in patients
      suffering from metabolic syndrome. Together with our studies to determine how AK
      production can be increased during Monascus fermentation, these data demonstrate
      the great potential of AK as a nutraceutical or therapeutic agent. 

PMID- 24728717
TI  - An intermolecular disulfide bond is required for thermostability and
      thermoactivity of beta-glycosidase from Thermococcus kodakarensis KOD1.
AB  - Scientists are interested in understanding the molecular origin of protein
      thermostability and thermoactivity for possible biotechnological applications.
      The enzymes from extremophilic organisms have been of particular interest in the
      last two decades. beta-glycosidase, Tkbetagly is a hyperthermophilic enzyme from
      Thermococcus kodakarensis KOD1. Tkbetagly contains two conserved cysteine
      residues, C88 and C376. The protein tertiary structure obtained through homology
      modeling suggests that the C88 residue is located on the surface whereas C376 is
      inside the protein. To study the role of these cysteine residues, we substituted
      C88 and C376 with serine residues through site-directed mutagenesis. The wild
      type and C376S protein existed in dimeric form and C88S in monomeric form, in an
      SDS-PAGE gel under non-reducing conditions. Optimal temperature experiments
      revealed that the wild-type was active at 100  degrees C whereas the C88S mutant
      exhibited optimal activity at 70  degrees C. The half-life of the enzyme at 70 
      degrees C was drastically reduced from 266 h to less than 1 h. Although C88 was
      not present in the active site region, the kcat/Km of C88S was reduced by 2-fold.
      Based on the structural model and biochemical properties, we propose that C88 is
      crucial in maintaining the thermostability and thermoactivity of the Tkbetagly
      enzyme.

PMID- 24728718
TI  - Biosynthetic trends and future aspects of bimetallic nanoparticles and its
      medicinal applications.
AB  - Recently, in all over the world, nanotechnology plays a major role in various
      applications. Most of the researchers focused their work on bimetallic
      nanoparticles due to their several modes or mechanisms of synthesis such as
      chemical, physical, and biosynthesis methods. These nanoparticles are of great
      interest due to their enormous applications and catalytic activities. Currently,
      syntheses of bimetallic nanoparticles using different sources of natural products
      are focused due to their advantage of being nontoxic to human and environment. To
      our knowledge, there is no report on the review of bimetallic nanoparticles and
      their medicinal applications. Taking this fact into account, we discussed the
      various synthesizing methods of bimetallic nanoparticles and their application
      related to biology. 

PMID- 24728719
TI  - Nociceptin system as a target in sepsis?
AB  - The nociceptin system comprises the nociceptin receptor (NOP) and the ligand
      nociceptin/orphanin FQ (N/OFQ) that binds to the receptor. The archetypal role of
      the system is in pain processing but the NOP receptor is also expressed on immune
      cells. Activation of the NOP receptor is known to modulate inflammatory
      responses, such as mast-cell degranulation, neutrophil rolling, vasodilation,
      increased vascular permeability, adhesion molecule regulation and leucocyte
      recruitment. As there is a loss of regulation of inflammatory responses during
      sepsis, the nociceptin system could be a target for therapies aimed at modulating
      sepsis. This review details the known effects of NOP activation on leucocytes and
      the vascular endothelium and discusses the most recent human and animal data on
      the role of the nociceptin system in sepsis. 

PMID- 24728720
TI  - Pulsed radiofrequency under ultrasound guidance for the tarsal tunnel syndrome:
      two case reports.
AB  - Tarsal tunnel syndrome (TTS) is a compression neuropathy that results from
      entrapment of the posterior tibial nerve or its branches. TTS may be treated
      either by conservative measures, including physical therapy, medications, and
      steroid injections, or by surgical decompression. Despite a variety of
      treatments, a few cases of TTS will relapse, and many cases of recurrent TTS will
      require re-operation. Pulsed radiofrequency (PRF) is known to have a number of
      advantages for pain management, particularly as this technique does not cause
      neural compromise such as motor weakness. Here, we report a new application of
      ultrasound-guided PRF in two cases of intractable TTS. Both patients had a long
      duration of severe foot pain and had been treated with various therapeutic
      modalities without lasting relief. We applied ultrasound-guided PRF to the
      affected posterior tibial nerve in each patient, and both had significantly
      reduced pain intensity scores and analgesic requirements without any
      complications. Ultrasound-guided PRF for intractable TTS relieved severe foot
      pain. It may supersede surgery as a reliable treatment for intractable TTS. 

PMID- 24728721
TI  - In vitro all-trans retinoic acid sensitivity of acute myeloid leukemia blasts
      with NUP98/RARG fusion gene.

PMID- 24728725
TI  - Neutrophil elastase inhibitor reduces ventilation-induced lung injury via nuclear
      factor-kappaB and NF-kappaB repressing factor in mice.
AB  - Mechanical ventilation used in patients with acute lung injury can damage
      pulmonary epithelial cells through production of inflammatory cytokines, oxygen
      radicals, and neutrophil infiltration, termed ventilator-induced lung injury.
      Neutrophil elastase, nuclear factor-kappaB (NF-kappaB), and NF-kappaB repressing
      factor (NRF) have previously been shown to participate in the regulation of
      macrophage inflammatory protein-2 (MIP-2) during airway inflammation. However,
      the mechanisms regulating interactions among mechanical ventilation, neutrophil
      influx, and NF-kappaB/NRF remain unclear. Thus, we hypothesized that neutrophil
      elastase inhibitor attenuated ventilation-induced neutrophil recruitment and MIP
      2 production through inhibition of the NF-kappaB/NRF pathway. Male C57BL/6 mice
      were exposed to low-tidal-volume (6 mL/kg) or high-tidal-volume (30 mL/kg)
      mechanical ventilation using room air with or without 2 ug/g NF-kappaB inhibitor
      SN50 or 6 ug/g NRF short interfering RNA or 100 ug/g neutrophil elastase
      inhibitor administration. Nonventilated mice served as a control group. Evan blue
      dye, lung wet-to-dry weight ratio, free radicals, myeloperoxidase,
      histopathologic grading of lung tissue, inflammatory cytokines, Western blot of
      NF-kappaB and NRF, and gene expression of NRF were measured to establish the
      extent of lung injury. Neutrophil elastase inhibitor ameliorated high-tidal
      volume ventilation-induced lung injury, neutrophil influx, production of MIP-2
      and malondialdehyde, activation of NF-kappaB and NRF, apoptotic epithelial cell
      death, and disruption of bronchial microstructure in mice. Mechanical stretch
      augmented acute lung injury was also attenuated through pharmacological
      inhibition of NF-kappaB activity by SN50 and NRF expression by NRF short
      interfering RNA. Our data suggest that neutrophil elastase inhibitor attenuates
      high-tidal-volume mechanical ventilation-induced neutrophil influx, oxidative
      stress, and production of MIP-2, at least partly, through inhibition of NF
      kappaB/NRF pathway. Understanding the protective effects of neutrophil elastase
      inhibitor associated with the reduction of MIP-2 allow clarification of the
      pathophysiological mechanisms regulating severe lung inflammation and development
      of possible therapeutic strategies involved in acute lung injury.

PMID- 24728724
TI  - Ontogeny of inter-alpha inhibitor proteins in ovine brain and somatic tissues.
AB  - Inter-alpha inhibitor proteins (IAIPs) found in relatively high concentrations in
      human plasma are important in inflammation. IAIPs attenuate brain damage in young
      and adult subjects, decrease during sepsis and necrotizing enterocolitis in
      premature infants, and attenuate sepsis-related inflammation in newborn rats.
      Although a few studies have reported adult organ-specific IAIP expression,
      information is not available on age-dependent IAIP expression. Given evidence
      suggesting IAIPs attenuate brain damage in young and adult subjects, and
      inflammation in newborns, we examined IAIP expression in plasma, cerebral cortex
      (CC), choroid plexus (CP), cerebral spinal fluid (CSF), and somatic organs in
      fetal, newborn, and adult sheep to determine the endogenous expression patterns
      of these proteins during development. IAIPs (enzyme-linked immunosorbent assay)
      were higher in newborn and adult than fetal plasma (P < 0.05). Western immunoblot
      detected 125 kDa PaI (Pre-alpha Inhibitor) and 250 kDa IaI (Inter-alpha
      Inhibitor) in plasma, CNS, and somatic organs. PaI expression in CC and CP was
      higher in fetuses than newborns and adults, but IaI expression was higher in
      adults than fetuses and newborns. Both PaI and IaI were higher in fetal than
      newborn CSF. IAIPs exhibited organ-specific ontogenic patterns in placenta,
      liver, heart, and kidney. These results provide evidence for the first time that
      plasma, brain, placenta, liver, heart, and kidney express IAIPs throughout ovine
      development and that expression patterns are unique to each organ. Although exact
      functions of IAIPs in CNS and somatic tissues are not known, their presence in
      relatively high amounts during development suggests their potential importance in
      brain and organ development.

PMID- 24728727
TI  - Intravascular ultrasound evidence of perivascular trauma during routine
      percutaneous coronary intervention.
AB  - We assessed whether intravascular ultrasound (IVUS) can detect evidence of
      coronary perforation that is not visible by coronary angiography. Approximately
      15,000 consecutive percutaneous coronary interventions (PCI) performed with IVUS
      guidance were reviewed retrospectively, pre- and post-PCI IVUS images were
      compared, and IVUS findings were compared with coronary angiography and in
      hospital outcomes. We detected three distinct patterns that were not present pre
      PCI and that were suggestive of perforation or perivascular trauma: perivascular
      blood speckle in 67 % (51/76), perivascular hematoma in 17 % (13/76), and new
      echolucent perivascular layer in 16 % (12/76). Angiographic appearance included
      perforation in 24 % (18/76), dissection in 33 % (25/76), lumen irregularity in 17
      % (13/76), new stenosis in 5 % (4/76), and no abnormalities in 21 % (16/76). The
      site of a break in arterial wall with communication between the lumen and
      perivascular space could be detected in 61 % (46/76). This extended proximally
      and distally with equal frequency, but was primarily located within the lesion in
      80 % (61/76), although the lumen was rarely compromised. Within 24 h, there were
      four emergent coronary artery bypass grafting procedures, one repeat PCI, and six
      periprocedural myocardial infarctions (defined as CK-MB >=10 times the upper
      limit of normal), but there were no episodes of cardiac tamponade. Although
      infrequent, IVUS detected three distinct patterns of post-PCI perivascular trauma
      suggestive of a perforation that was detected angiographically in only 24 % of
      cases.

PMID- 24728730
TI  - Is it time to validate the prognostic role of F-18-FDG PET/CT scan in thymic
      epithelial tumors?

PMID- 24728731
TI  - Reply to 'Is it time to validate the prognostic role of F-18-FDG PET/CT scan in
      thymic epithelial tumors?'.

PMID- 24728732
TI  - Uncemented metal-back glenoid component in revision of aseptic glenoid loosening:
      a prospective study of 10 cases with a minimum follow-up of 2 years.
AB  - INTRODUCTION: Glenoid component loosening comprises 25 % of all complications
      related to total shoulder arthroplasties (TSA). This prospective study was
      undertaken to assess the accuracy of an uncemented metal-back glenoid component
      in cases of revision of aseptic glenoid loosening. MATERIALS AND METHODS: Between
      September 2007 and January 2010, a total of ten patients with symptomatic glenoid
      loosening after TSA (7 cemented and 3 non-cemented) underwent revision surgery
      with an uncemented metal-back glenoid component (MB). The rotator cuff was
      functional in all cases. The reconstruction of the glenoid was obtained using an
      iliac crest graft (8 patients) or synthetic bone substitute (2 patients). The non
      cemented glenoid component was fixed into the glenoid native bone, thus
      stabilizing the graft reconstruction. A clinical and radiological checkup was
      performed at the long-term follow-up and compared with the preoperative values.
      The patients were also asked to quantify their pain and satisfaction. RESULTS:
      There were no intraoperative complications. In all cases, the radiological
      evaluation showed a good integration of the bone graft with no radiolucency or
      new glenoid loosening. In one patient, the revision surgery was indicated for the
      dissociation between MB and polyethylene. After more than 2 years of follow-up,
      all patients were satisfied or highly satisfied with the outcomes. The pain VAS
      score (0-10) decreased from 5.1 to 0.6 (p < 0.001). The simple shoulder test
      increased from 3.4 to 7.9 points (gain 4.5; p < 0.001). The Constant and Murley
      score increased from 39.4 to 71 points (gain 31.6; p < 0.001). The gain in
      anterior elevation was 31 degrees , from 118 degrees  to 149 degrees  (p <
      0.001). External rotation elbow to the body (ER1) increased from an average of 34
      degrees  preoperatively to 47 degrees  after surgery (p < 0.001) and external
      rotation at 90 degrees  of abduction from 43 degrees  to 66 degrees  (p < 0.001).
      CONCLUSION: This study suggests that revision with a non-cemented glenoid
      component associated with a bone graft can solve the difficult challenge of
      glenoid loosening, provided that the rotator cuff is functional and the glenoid
      is reconstructable. LEVEL OF EVIDENCE AND STUDY TYPE: Cohort studies
      (prospective) without controls, Level IV.

PMID- 24728733
TI  - Early postoperative transtibial articular fistula formation after anterior
      cruciate ligament reconstruction: a review of three cases.
AB  - INTRODUCTION: This is a retrospective case report of three cases with an early
      postoperative transtibial fistula after anterior cruciate ligament reconstruction
      (ACL). MATERIALS AND METHODS: The patients had undergone ACL reconstruction and
      complained of fluid drainage through the not-healed wound or swelling localized
      on the anteromedial aspect of the ipsilateral proximal tibia during the early
      postoperative. Magnetic resonance imaging showed a multilocular fluid-filled cyst
      arising from the distal hole of the tibial bone tunnel. Open resection of the
      fistula and the cyst was performed in all cases and communication between the
      tibial tunnel and the joint space was confirmed. During revision surgery the
      distal hole of the tibial tunnel was covered with a fascio-periosteal flap.
      RESULTS: All wounds healed without complications. There was no recurrence of
      drainage or cyst formation. At 2 years follow-up the knee function was normal and
      was not affected by the complication in any of the patients. Early postoperative
      transtibial fistulae after ACL reconstruction are rare complications that
      clinically present either as anterior tibial cysts or persistent wound drainage.
      Surgical treatment is required, and some delay in the rehabilitation routine is
      required, but the final outcome is not affected.

PMID- 24728734
TI  - Invasive breast carcinomas of no special type with osteoclast-like giant cells
      frequently have a luminal phenotype.
AB  - Invasive carcinoma of no special type (NST) with osteoclast-like giant cells
      (OGCs) represents a unique type of breast neoplasm, characterized by the presence
      of multinucleated OGCs and a vascularized, hemorrhagic stroma. Because of its
      rarity, the literature regarding this tumor remains limited and a detailed
      immunophenotype of this tumor has not been established as yet. We report a
      clinicopathological and immunohistochemical study of 42 patients with invasive
      carcinoma NST with OGCs. Macroscopically, these tumors presented as a well
      delimited red-brown mass. A remarkable feature of the tumor was the presence of
      OGCs in the fibroblastic or hemorrhagic vascular stroma, as well as in the
      adjacent tumor nests or glandular lumina. The number of OGCs varied from 8 to 105
      per 10 high-power fields with an average of 48. The tumors were well to
      moderately differentiated. Cribriform architecture was observed in 27 tumors (63
      %). All of the 36 available tumors were of luminal phenotype, according to the
      Ki67 labeling index 89 % luminal A and 11 % luminal B. With a mean follow-up time
      of 46.4 months, lung metastasis was found in 2 patients (5 %) at 7 and 11 years
      after the operation, respectively. None of the other cases had presented with
      evidence of recurrence or metastasis. To the best of our knowledge, this is the
      largest reported series of invasive carcinoma NST with OGCs as yet. Our study
      revealed that invasive carcinoma NST with OGCs exhibit a luminal phenotype with
      luminal A subtype as the major group. 

PMID- 24728737
TI  - Erythema multiforme associated with Mycoplasma pneumoniae.

PMID- 24728736
TI  - Intrathecal/intraventricular colistin in external ventricular device-related
      infections by multi-drug resistant Gram negative bacteria: case reports and
      review.
AB  - We report three cases of external ventricular derivation infections caused by
      multidrug-resistant Gram-negative rods and treated successfully with
      intraventricular colistin. The intrathecal or intraventricular use of colistin
      have been reported in more than 100 cases without any consensus on dosage,
      duration and type (monotherapy or combination therapy) of treatment. Based on our
      comprehensive review of the relevant literature relating to both clinical and
      pharmacokinetic data, we conclude that the intrathecal/intraventricular
      administration of colistin is a safe and effective option to treat central
      nervous system infections caused by multidrug-resistant Gram-negative bacteria. 

PMID- 24728738
TI  - Nuclear Notch3 expression is associated with tumor recurrence in patients with
      stage II and III colorectal cancer.
AB  - BACKGROUND: The importance of Notch signaling in colorectal cancer (CRC)
      tumorigenesis has been recently recognized. However, the significance of Notch3
      expression and its association with Notch1 expression in CRC is unclear. In the
      present study, we investigated Notch1 and Notch3 expression in Stage II and III
      CRC to assess their association with clinicopathological characteristics.
      METHODS: The protein expression of Notch1 and Notch3 was examined using
      immunohistochemistry in 305 CRC specimens. Nuclear expression of Notch1 and
      Notch3 and their associations with clinicopathological characteristics and
      distant relapse-free survival (dRFS) were evaluated. RESULTS: Nuclear Notch1 was
      overexpressed in 37 % of specimen, and nuclear Notch3 in 38 %. Nuclear Notch3
      expression correlated with tumor differentiation status (P = 0.0099). Nuclear
      expression of Notch1 and Notch3 was associated with tumor recurrence (P = 0.0311
      and P = 0.0053, respectively). In multivariate analysis, nuclear Notch3
      expression [hazard ratio (HR) = 1.71; 95 % confidence interval (CI), 1.06-2.78; P
      = 0.0271), lymph node metastasis, and venous involvement were independently
      correlated with dRFS. In subgroup analysis, nuclear Notch3 expression was
      strongly associated with dRFS in Stage II CRC (HR = 3.47; 95 % CI 1.44-9.22; P =
      0.0055). Both nuclear Notch1 and Notch3 were positive in 67 specimens (22 %) and
      both were negative in 144 specimens (47 %). Coexpression of nuclear Notch1 and
      Notch3 had an additive effect toward poorer dRFS compared with a negative subtype
      (HR = 2.48; 95 % CI, 1.41-4.40; P = 0.0019). CONCLUSIONS: Nuclear Notch3
      expression might be a novel predictive marker for recurrence in Stage II and III
      CRC.

PMID- 24728739
TI  - Impact of bilateral versus unilateral mastectomy on short term outcomes and
      adjuvant therapy, 2003-2010: a report from the National Cancer Data Base.
AB  - BACKGROUND: Rates of bilateral mastectomy (BM) have increased, but the impact on
      length of stay (LOS), readmission rate, 30-day mortality, and time to adjuvant
      therapy is unknown. METHODS: Using the National Cancer Data Base, we selected
      390,712 non-neoadjuvant AJCC stage 0-III breast cancer patients who underwent
      either unilateral mastectomy (UM) or BM from 2003 to 2010 with and without
      reconstruction. We used chi-square and logistic regression models for the
      analysis. RESULTS: A total of 315,278 patients (81 %) had UM, and 75,437 (19 %)
      had BM; 97,031 (25 %) underwent reconstruction. The number of median days from
      diagnosis to UM increased from 19 days in 2003 to 28 days in 2010, and for BM,
      increased from 21 to 31 days (p < 0.001). BM was independently associated with a
      longer time to surgery when adjusting for patient, facility, and tumor factors
      and reconstruction (OR 1.11; 95 % CI 1.07-1.15; p < 0.001). Reconstructed
      patients were twice as likely to have a longer time to surgery (OR 2.07; 95 % CI
      2.01-2.14; p < 0.001). The median LOS was 1 day (range 0-184 days) for UM versus
      2 (range 0-182) for BM (p < 0.001); 30-day mortality and readmission rates were
      not different between BM and UM. The median number of days from diagnosis to
      definitive chemotherapy, hormonal therapy, and radiation therapy was
      significantly greater in the BM group. CONCLUSIONS: Delays to surgical and
      adjuvant treatment are significantly longer for BM irrespective of
      reconstruction, and these delays have increased over the study period. These
      findings can be used by clinicians to counsel patients on BM.

PMID- 24728740
TI  - Comparison of survival of patients with BCLC stage A hepatocellular carcinoma
      after hepatic resection or transarterial chemoembolization: a propensity score
      based analysis.
AB  - BACKGROUND: It is unclear whether hepatic resection (HR) or transarterial
      chemoembolization (TACE) is associated with better outcomes for patients with
      hepatocellular carcinoma (HCC) in Barcelona Clinic Liver Cancer (BCLC) stage A.
      The present study compared survival for patients with BCLC stage A HCC treated by
      HR or TACE. METHODS: Our study examined 360 patients treated by HR and 221
      treated by TACE. To reduce bias in patient selection, 152 pairs of propensity
      score-matched patients were generated, and their long-term survival was compared
      using the Kaplan-Meier method. Independent predictors of survival were identified
      using the Cox proportional hazards model. RESULTS: Among propensity-score-matched
      pairs of patients with Child-Pugh A liver function who were treated by HR or
      TACE, the 1-, 3-, and 5-year overall survival rates were 75.5, 44.8, and 30.2 %
      after HR and 64.5, 24.1, and 13.7 % after TACE (P < 0.001). Serum AST level,
      serum AFP level, tumor size, and TACE independently predicted survival in Cox
      regression analysis. CONCLUSIONS: Our propensity-score-matched study confirmed
      that HR was associated with higher survival rates than was TACE in patients with
      BCLC stage A HCC.

PMID- 24728741
TI  - Insight into mucinous colorectal carcinoma: clues from etiology.
AB  - The prognostic impact of mucinous carcinoma (MC) in colorectal cancer (CRC) has
      been subject to debate ever since the introduction of the classification of
      tumors according to their histological differentiation. MC is a distinct clinical
      and pathological entity within the spectrum of CRC and accounts for approximately
      10-15 % of cases. Factors involved in MC development have not been completely
      understood, but clinical observations may lead to a better insight into the
      etiology of MC. In this article, we provide an in-depth review of the literature
      regarding etiological aspects of MC. We show that there are worldwide differences
      in the prevalence of MC, with low rates in Asian countries and higher rates in
      the western world. Moreover, MC is more commonly diagnosed in patients suffering
      from inflammatory bowel diseases or Lynch syndrome and an increased rate of MC is
      observed in patients with radiotherapy-induced CRCs. These findings are
      suggestive of a different oncogenic development. Identification of conditions
      that are associated with MC generates insight into the etiological pathways
      leading to the development of this special subtype.

PMID- 24728742
TI  - Ultrafine fibrous gelatin scaffolds with deep cell infiltration mimicking 3D ECMs
      for soft tissue repair.
AB  - In this research, ultrafine fibrous scaffolds with deep cell infiltration and
      sufficient water stability have been developed from gelatin, aiming to mimic the
      extracellular matrices (ECMs) as three dimensional (3D) stromas for soft tissue
      repair. The ultrafine fibrous scaffolds produced from the current technologies of
      electrospinning and phase separation are either lack of 3D oriented fibrous
      structure or too compact to be penetrated by cells. Whilst electrospun scaffolds
      are able to emulate two dimensional (2D) ECMs, they cannot mimic the 3D ECM
      stroma. In this work, ultralow concentration phase separation (ULCPS) has been
      developed to fabricate gelatin scaffolds with 3D randomly oriented ultrafine
      fibers and loose structures. Besides, a non-toxic citric acid crosslinking system
      has been established for the ULCPS method. This system could endow the scaffolds
      with sufficient water stability, while maintain the fibrous structures of
      scaffolds. Comparing with electrospun scaffolds, the ULCPS scaffolds showed
      improved cytocompatibility and more importantly, cell infiltration. This research
      has proved the possibility of using gelatin ULCPS scaffolds as the substitutes of
      3D ECMs. 

PMID- 24728743
TI  - Osteoblast attachment to hydroxyapatite micro-tube scaffolds.
AB  - Tissue engineering offers a novel route for repairing damaged or diseased tissue
      by incorporating the patient's own healthy cells or donated cells into temporary
      scaffolds that act as a matrix for cell cultivation. Tissue scaffolds that are
      biocompatible and are porous with interconnected porous channels for cell
      ingrowth with a suitable degradation rate would be advantageous. In this study
      hydroxyapatite micro-tubes produced using the biomimetic coating technique will
      be pressed into a tissue scaffold. A compaction and sintering study will be done
      to observe appropriate pressure and heat treatment to produce a mechanically
      stable scaffold material. The ideal pressure was found to be 2.5 MPa where the
      tube-like structure was maintained, high porosity was achieved and suitable
      strength was possible. Sintering between 1,000 and 1,100  degrees C was found to
      produce good results. The average porosity for the chosen pressure of 2.5 MPa was
      68%. The scaffold was observed with SEM, micro tomography (micro-CT), chemical
      analysis and degradation testing. Porous channels were established using micro-CT
      where the porous channels were roughly 100 um. Chemical analysis showed constant
      release of calcium and phosphorous, and far below toxic levels of heavy metals
      from the die. Degradation testing showed high degradation compared to tested
      commercially available materials. Cell culturing was done on the scaffold to
      characterise the biological performance of the scaffolds. Cell culturing was done
      in a 7 and 24 day cell culture to examine cell morphology and cell ingrowth. The
      results showed cell ingrowth into a micro-tube and cell orientation in a
      longitudinal direction. SEM, confocal microscopy and histology were employed as
      characterisation tools for observing cell ingrowth.

PMID- 24728744
TI  - Association between family history and herpes zoster: a case-control study.
AB  - BACKGROUND: There are many risk factors besides age and immune suppression for
      herpes zoster. Family history as a risk factor is suggested in some recent
      studies. The aim of this study was to evaluate the association between herpes
      zoster and family history. METHODS: This case-control study was undertaken in
      Farshchian Hospital, Hamadan, Iran. "Case group" included patients with confirmed
      diagnosis of herpes zoster. "Control group" was chosen among other dermatologic
      patients or their companions without any history of herpes zoster. Immune
      deficiency was the main excluding criteria. Information about age, gender,
      dermatome involved (only in patient group), history of chronic dermatologic or
      systemic diseases and family history of herpes zoster was asked using special
      questionnaires. RESULTS: Case and control groups included 217 and 200
      participants respectively. Mean age of cases and controls was 49.08+/-15.59 and
      49.96+/-15.54 years old respectively (P=0.936). 53.5% of cases and 54.5% of
      controls were women (P=0.845). Most frequent dermatomes involved in patients were
      thoracic (85/217; 39.25%) and cervical dermatomes (55/217; 25.3%). Frequency of
      herpes zoster in first-degree blood relatives in cases and controls was 65/217
      (30%) and 16/200 (8%) respectively (OR=4.91; 95% CI: 2.73, 8.85; P=0.001).
      CONCLUSIONS: Our findings indicated a significantly higher proportion of patients
      with family history of herpes zoster comparing to controls. This study confirms
      family history as a risk factor for herpes zoster. Therefore, the old patients
      with positive family history of herpes zoster may be appropriate candidates for
      vaccination with Zostavax. However, more evidence based on large cohort studies
      in needed to confirm our findings.

PMID- 24728745
TI  - Global epidemic trend of tuberculosis during 1990-2010: using segmented
      regression model.
AB  - BACKGROUND: Tuberculosis (TB) is a pandemic disease. It is the second leading
      cause of death from infectious diseases after human immunodeficiency virus (HIV)
      in the world.The main objective of this paper was to determine and compare the
      epidemiology of TB incidence rate and its trend changes during 1990-2010 in six
      WHO regions regarding age, gender and income levels. METHODS: The Average Annual
      Percent Change (AAPC) and Annual Percent Change (APC) of TB incidence, mortality,
      treatment-successes, case detection rates, as well as change points of trend was
      estimated using segmented regression model. The number of change points was
      selected by the permutation procedure based on likelihood ratio test. RESULTS:
      Two change points for global TB incidence rate trend with AAPC5years equaling 
      1.4 % was estimated, the maximum AAPC5years of six regions was attributed to the
      American region (-3.5%). AACP of TB treatment-successes rate for Eastern
      Mediterranean (+2.2), the Americas (+1.6), south East Asia (+.8) and Global
      (+1.1) were significant (P<0.05). Moreover AACP5years of TB case detection rate
      for South East Asia (+7.5), Eastern Mediterranean (+4.9), Africa (+2.8) and the
      Americas (+1.7) were significant (P<0.05). Globally, all of income categories had
      descending trend of TB incidence and mortality rate, except the upper-middle
      income level that had ascending incidence trend (AAPC=+0.7%). CONCLUSIONS:
      Globally, TB incidence and mortality rates have downturn trend and TB treatment
      successes and detection rates have upward trend, but their changes rate are
      insufficient to reach the goal of TB stop strategy. The economic levels have
      effect on trend, with no clear pattern, so it seems necessary that evaluation TB
      control programs based on characteristics of countries for reach TB control
      goals.

PMID- 24728746
TI  - Cost-effectiveness of rabies post exposure prophylaxis in Iran.
AB  - BACKGROUND: The rabies is one of the most important officially-known viral
      zoonotic diseases for its global distribution, outbreak, high human and
      veterinary costs, and high death rate and causes high economic costs in different
      countries of the world every year. The rabies is the deadliest disease and if the
      symptoms break out in a person, one will certainly die. However, the deaths
      resulting from rabies can be prevented by post-exposure prophylaxis. To do so, in
      Iran and most of the countries in the world, all the people who are exposed to
      animal bite receive Post-Exposure Prophylaxis (PEP) treatment. The present survey
      aimed to investigate the cost-effectiveness of PEP in southern Iran. METHODS: The
      present study estimated the PEP costs from the government's Perspective with step
      down method for the people exposed to animal bite, estimated the number of DALYs
      prevented by PEP in the individuals using decision Tree model, and computed the
      Incremental cost-effectiveness Ratio. The information collected of all reported
      animal bite cases (n=7111) in Fars Province, who referred rabies registries in
      urban and rural health centers to receive active care. Performing the PEP program
      cost estimated 1,052,756.1 USD for one  year and the estimated cost for the
      treatment of each animal bite case and each prevented death was 148.04 and
      5945.42 USD, respectively. Likewise 4,509.82 DALYs were prevented in southern
      Iran in 2011 by PEP program. RESULTS: The incremental cost-effectiveness ratio
      for each DALY was estimated to be 233.43 USD. In addition to its full
      effectiveness in prophylaxis from rabies, PEP program saves the financial
      resources of the society, as well. CONCLUSIONS: This study showed performing PEP
      to be more cost-effective.

PMID- 24728747
TI  - Seroprevalence of Bordetella pertussis antibody in pregnant women in Iran.
AB  - BACKGROUND: The increasing incidence of pertussis among adolescents and adults in
      recent years is an alarming factor in transmission of the infection to non-immune
      infants and children. Vaccination of pregnant women, immediately after delivery
      and before being discharged from the hospital may help to protect mothers and
      their newborns against the disease. Decision making process, regarding maternal
      immunization, requires credible information and knowledge about seroepidemiology
      of the infection in pregnant women. The aim of this study was to determine the
      seroprevalence of Bordetella pertussis antibody among admitted pregnant women in
      Hamadan, western Iran. METHODS: In this cross-sectional study, 288 pregnant women
      admitted to the Fatemiyeh Hospital, Hamadan, western Iran, were enrolled into the
      study. After obtaining consent from every patient, serum samples were taken from
      patients and were kept frozen until testing. Serum level of B. pertussis antibody
      was measured using ELISA. Level of antibody higher than 24 U/ml was considered
      positive. The obtained data were analyzed using the statistical software SPSS.
      RESULTS: From 288 pregnant women, 126 (43.8%) were in their second trimester.
      Serological results in 103 patients (35.8%) were positive. The mean age of
      mothers with positive serology was 27.5+/-6 years old. Thirty-five percent of
      patients had a valid immunization record, and 1.57% of those with no vaccination
      record had a positive serology. CONCLUSIONS: The level of immunity against B.
      pertussis in pregnant women was low. Immunization before or during pregnancy can
      stimulate newborn's immune response and gives them required protection against
      pertussis infection.

PMID- 24728748
TI  - Designing a new computer mouse and evaluating some of its functional parameters.
AB  - BACKGROUND: This study aimed to design a new mouse and evaluate some of its
      functional parameters. The prototype of an ergonomic mouse was made according to
      design principles. METHODS: The study was conducted from 2011 to 2013 in the
      Department of Ergonomics in Shiraz University of Medical Science. Functional
      parameters including Movement Time (MT) and error rate of the new mouse were
      evaluated by 10 participants based on ISO 9241-9 standard. RESULTS: The
      application of design principles in the new mouse resulted in improving MT and
      error rate so that they could be comparable to those of a standard mouse. MT, in
      both the standard and the new mouse was 0.846 and 0.864 s, respectively. Error
      rate of the standard and the new mouse was reported as 13% and 19%, respectively.
      Statistical analysis showed no significant difference between the two mice from
      these perspectives. CONCLUSIONS: Apparently, the studied functional parameters of
      the new mouse were similar to those of the standard one. The new mouse could be
      an appropriate substitution for the standard mouse without losing its positive
      characteristics.

PMID- 24728749
TI  - Evaluation of IFN-gamma polymorphism in visceral leishmaniasis.
AB  - BACKGROUND: Leishmaniasis is a tropical disease that is endemic in some areas of
      Iran, including East Azerbaijan. IFN-gamma is one of the cytokines that triggers
      cell-mediated immunity, thus initiating elimination of the infection. This case
      control study was performed to investigate the association between the
      polymorphism of the IFN-gamma gene at the +874A/T locus and visceral
      leishmaniasis (VL). METHODS: In this study conducted during 2012-2013, 267
      participants were selected from individuals living in an endemic area of VL.
      Subjects were divided into three groups; 86 patients with VL, 82 seropositive
      individuals without any history of leishmaniasis, and 99 seronegative healthy
      controls. Genotyping of the IFN-gamma +874A/T polymorphism was carried out using
      an Amplification Refractory Mutation System-PCR (ARMS-PCR). RESULTS: The
      frequency of the +874A allele in the patient group (75.5%) was higher than in the
      seropositive individuals (54%). The highest frequency of the +874T/T genotype was
      observed in seropositive individuals, while the patient group had the lowest
      frequency (34.1% vs. 24.5%). However, these differences were not significant.
      CONCLUSIONS: There was no significant association between IFN-gamma +874A/T
      polymorphism and VL.

PMID- 24728750
TI  - Reliability and validity of a safety climate questionnaire.
AB  - BACKGROUND: It is believed that improved safety culture/climate is a fundamental
      element to accident prevention. Therefore, development a scale to assess safety
      climate is a step towards accident control. The purpose of this study was to
      construct a Persian safety climate questionnaire. METHODS: The study took place
      in Tehran and Esfahan oil refineries in Iran in 2010. An initial questionnaire
      was formed from two previous studies. This tool was translated to Persian based
      on back translation. The 61-item questionnaire was tested on operational staffs
      (N=324). Principle component analysis and Varimax with Kaiser Normalization was
      used to extract factors, in statistical software package SPSS 11.0. RESULTS: The
      factors were obtained as Management Commitment to Safety and personnel
      collaboration 23 variables, 17.33 % of the variance, Safety communication five
      items, 6.97% of the variance, Supportive environment five items, 6.245% of the
      variance, Work Environment six items, 5.590% of the variance, Formal Training
      four items, 4.581% of the variance, Priority of Safety five items, 4.177% of the
      variance, Personal Priorities and Need for Safety three items, 3.333% of the
      variance. CONCLUSIONS: Achievement of a valid and reliable safety climate tool
      may bring enormous benefits to the refineries. However, a reliable and valid tool
      to measure safety climate could be useful in other refineries. Moreover, the
      generic nature of the safety climate scale may grant its use for other
      workplaces.

PMID- 24728751
TI  - Comparison of small area techniques for estimating prevalence of mental disorder
      symptoms among Iranian's southern adolescents.
AB  - BACKGROUND: Mental disorders may lead to several complications in adolescents'
      people whose compensation is very difficult and sometime impossible. They are
      prone to emotional problems. Therefore, knowing prevalence of diseases and valid
      statistical technique is necessary to plan for prevention and control of
      diseases. METHODS: In this cross-sectional study; direct, synthetic, and post
      stratified estimation as small area methods were used to compute mental disorder
      symptoms (MDS) prevalence with county-level reference among adolescents in south
      of Iran. We conducted Mental Health Study data (MHS) conducted in Bushehr
      Province, southern Iran in 2005 for individual-level classification of MDS
      (n=2584). Students were in grade 9, 10 and 11, and enrolled with complete
      satisfaction. RESULTS: The synthetic method was superior to the direct and post
      stratified technique with respect to discrepancy statistics such as MSE and width
      95% confidence interval (MSEs(synthetic)~0.001, MSEs(post-stratified)~0.010,
      MSEs(direct)~0.100). In addition, the width range of 95% confidence intervals for
      all county estimates was 9.7% to 65.3% based on in direct methods. Besides, the
      width range of 95% confidence intervals for all county estimates under post
      stratified and synthetic method was 16.7% to 62.2% and 11.8 %-25.1%,
      respectively. Hence, we could categorize prevalence of mental disorder symptoms
      in Bushehr's counties into five categories based-on synthetic methods. Maximum
      and minimum prevalence belongs to Geneveh (0.403) and Dashty (0.398) counties,
      respectively. CONCLUSIONS: The MHS cannot be used as a valid source of county
      level mental health prevalence data and the small-area method such synthetic
      method should be used to estimate prevalence of mental disorder symptoms in
      county-level. Furthermore, the synthetic method improved MDS prevalence more than
      direct and post-stratified methods.

PMID- 24728752
TI  - Health care cost disease as a threat to Iranian aging society.
AB  - BACKGROUND: Because of the rapid aging rate, the share of health expenditure in
      gross domestic product rises irreversibly and increases concern among politicians
      and the general public. The aim of this study was to examine the accuracy of the
      Baumol's model of unbalanced growth in Iran over the period 1981-2010. METHODS:
      This theoretical-analytical study was conducted in 2012 to investigate the
      various determinants of ongoing rise in the health expenditures. To this end, an
      Error Correction Model was derived from the long run cointegrating equation to
      inquire the veracity of Baumol's theory. RESULTS: Estimating the short run and
      long run equations by using time series data shows that the rate of increase in
      health expenditure is aligned with the difference between wage increases in and
      growth of productivity in the health sector. Besides, results show that both the
      per capita income and the inflation rate of health care had significant effects
      on raising the share of health sector in domestic economy. CONCLUSIONS: According
      to rapid population aging and existence of Baumol's cost disease in Iranian
      health sector, we predict much more rise in health expenditure in a few decades.

PMID- 24728753
TI  - Development of a noise prediction model based on advanced fuzzy approaches in
      typical industrial workrooms.
AB  - BACKGROUND: Noise prediction is considered to be the best method for evaluating
      cost-preventative noise controls in industrial workrooms. One of the most
      important issues is the development of accurate models for analysis of the
      complex relationships among acoustic features affecting noise level in workrooms.
      In this study, advanced fuzzy approaches were employed to develop relatively
      accurate models for predicting noise in noisy industrial workrooms. METHODS: The
      data were collected from 60 industrial embroidery workrooms in the Khorasan
      Province, East of Iran. The main acoustic and embroidery process features that
      influence the noise were used to develop prediction models using MATLAB software.
      Multiple regression technique was also employed and its results were compared
      with those of fuzzy approaches. RESULTS: Prediction errors of all prediction
      models based on fuzzy approaches were within the acceptable level (lower than one
      dB). However, Neuro-fuzzy model (RMSE=0.53dB and R2=0.88) could slightly improve
      the accuracy of noise prediction compared with generate fuzzy model. Moreover,
      fuzzy approaches provided more accurate predictions than did regression
      technique. CONCLUSIONS: The developed models based on fuzzy approaches as useful
      prediction tools give professionals the opportunity to have an optimum decision
      about the effectiveness of acoustic treatment scenarios in embroidery workrooms.

PMID- 24728754
TI  - Prevalence of anabolic steroid use and associated factors among body-builders in
      Hamadan, West province of Iran.
AB  - BACKGROUND: Androgenic-anabolic steroids (AAS) are abused by a growing number of
      bodybuilders. This descriptive cross-sectional study was conducted to determine
      prevalence and patterns of AAS use by bodybuilders in Hamadan, western Iran.
      METHODS: In this cross-sectional study, participants were recruited from five gym
      clubs in two area of Hamadan (a total of 10 clubs). Twenty-five bodybuilders from
      each club were administered. Questions investigating demographic information,
      sport history, education level, general knowledge about AAS, and their side
      effects were asked. Statistical analysis was performed using SPSS 16. RESULTS:
      The frequency of AAS use was 28.8% (72/250). Fifty-four percent of users were 25
      years or younger. AAS abuse showed a significant association with duration of
      exercise. The drugs were suggested mostly from peers (43.1%) and coaches (36.1%).
      The most commonly consumed anabolic steroid was testosterone (66.7%). The most
      commonly reported AAS side effect was acne (18.1%). There was not significant
      association between general knowledge about side effects of ASS and their use.
      CONCLUSIONS: The results of current survey indicate that frequency of ASS use is
      high in adolescents and young adult bodybuilders. Well educated bodybuilders have
      a higher prevalence of abuse. Awareness about the side effects of drugs is not
      deterrent factor for their abuse. Iranian Ministry of Sport and the Youth, and
      the National Council for Youth, should be urged to conduct more effective
      prevention strategies.

PMID- 24728755
TI  - Comment on: "Prevalence of diabetes in people aged >30 years: the results of
      screening program of Yazd province, Iran in 2012".

PMID- 24728756
TI  - Expression, purification, and biological activity of the recombinant pramlintide
      precursor.
AB  - Pramlintide is an artificially designed protein which has the same function as
      amylin in human body. This protein is extremely difficult to synthesize through
      prokaryotic expression method because of its two essential active sites,
      intrachain disulfide bond and C-terminal amide group. Since alpha-amidating
      monooxygenase is widely distributed in human and animal, it is possible to use
      pramlintide precursor with an additional C-terminal glycine (PAG), which is the
      potential substrate of alpha-amidating monooxygenase, for in vivo applications.
      The recombinant PAG was expressed in Escherichia coli using the small ubiquitin
      related modifier (SUMO) as the molecular chaperone, and the optimal fusion
      expression level reached to 36.3% of the total supernatant protein. Under optimal
      conditions in a 10-L fermentor, the recombinant PAG was obtained with a purity of
      greater than 95%, and the average expression level was reached to 20 mg/L. The
      authenticity and the intrachain disulfide bridge of PAG were confirmed by Western
      blotting and matrix-assisted laser desorption/ionization coupled to time-of
      flight mass spectrometry (MALDI-TOF MS) as well as N-terminal sequencing of
      protein. Based on an L6 myoblast cell model in vitro and an animal model of
      gastric emptying in vivo, the results of activity revealed that PAG showed a
      lower biological activity in vitro but has almost the same activity as the
      chemically synthesized pramlintide in vivo.

PMID- 24728757
TI  - The prominent role of fungi and fungal enzymes in the ant-fungus biomass
      conversion symbiosis.
AB  - Molecular studies have added significantly to understanding of the role of fungi
      and fungal enzymes in the efficient biomass conversion, which takes place in the
      fungus garden of leaf-cutting ants. It is now clear that the fungal symbiont
      expresses the full spectrum of genes for degrading cellulose and other plant cell
      wall polysaccharides. Since the start of the genomics era, numerous interesting
      studies have especially focused on evolutionary, molecular, and organismal
      aspects of the biological and biochemical functions of the symbiosis between leaf
      cutting ants (Atta spp. and Acromyrmex spp.) and their fungal symbiont
      Leucoagaricus gongylophorus. Macroscopic observations of the fungus-farming ant
      colony inherently depict the ants as the leading part of the symbiosis (the
      myrmicocentric approach, overshadowing the mycocentric aspects). However, at the
      molecular level, it is fungal enzymes that enable the ants to access the
      nutrition embedded in recalcitrant plant biomass. Our hypothesis is that the
      evolutionary events that established fungus-farming practice were predisposed by
      a fascinating fungal evolution toward increasing attractiveness to ants. This
      resulted in the ants allowing the fungus to grow in the nests and began to supply
      plant materials for more fungal growth. Molecular studies also confirm that
      specialized fungal structures, the gongylidia, with high levels of proteins and
      rich blend of enzymes, are essential for symbiosis. Harvested and used as ant
      feed, the gongylidia are the key factor for sustaining the highly complex leaf
      cutting ant colony. This microbial upgrade of fresh leaves to protein-enriched
      animal feed can serve as inspiration for modern biorefinery technology. 

PMID- 24728758
TI  - Improvement of DGGE analysis by modifications of PCR protocols for analysis of
      microbial community members with low abundance.
AB  - Denaturing gradient gel electrophoresis (DGGE) is a powerful technique to reveal
      the community structures and composition of microorganisms in complex natural
      environments and samples. However, positive and reproducible polymerase chain
      reaction (PCR) products, which are difficult to acquire for some specific samples
      due to low abundance of the target microorganisms, significantly impair the
      effective applications of DGGE. Thus, nested PCR is often introduced to generate
      positive PCR products from the complex samples, but one problem is also
      introduced: The total number of thermocycling in nested PCR is usually
      unacceptably high, which results in skewed community structures by generation of
      random or mismatched PCR products on the DGGE gel, and this was demonstrated in
      this study. Furthermore, nested PCR could not resolve the uneven representative
      issue with PCR products of complex samples with unequal richness of microbial
      population. In order to solve the two problems in nested PCR, the general
      protocol was modified and improved in this study. Firstly, a general PCR
      procedure was used to amplify the target genes with the PCR primers without any
      guanine cytosine (GC) clamp, and then, the resultant PCR products were purified
      and diluted to 0.01 MUg ml(-1). Subsequently, the diluted PCR products were
      utilized as templates to amplify again with the same PCR primers with the GC
      clamp for 17 cycles, and the products were finally subjected to DGGE analysis. We
      demonstrated that this is a much more reliable approach to obtain a high quality
      DGGE profile with high reproducibility. Thus, we recommend the adoption of this
      improved protocol in analyzing microorganisms of low abundance in complex samples
      when applying the DGGE fingerprinting technique to avoid biased results.

PMID- 24728760
TI  - Alginate/polyoxyethylene and alginate/gelatin hydrogels: preparation,
      characterization, and application in tissue engineering.
AB  - Hydrogels are attractive biomaterials for three-dimensional cell culture and
      tissue engineering applications. The preparation of hydrogels using alginate and
      gelatin provides cross-linked hydrophilic polymers that can swell but do not
      dissolve in water. In this work, we first reinforced pure alginate by using
      polyoxyethylene as a supporting material. In an alginate/PEO sample that contains
      20 % polyoxyethylene, we obtained a stable hydrogel for cell culture experiments.
      We also prepared a stable alginate/gelatin hydrogel by cross-linking a periodate
      oxidized alginate with another functional component such as gelatin. The
      hydrogels were found to have a high fluid uptake. In this work, preparation,
      characterization, swelling, and surface properties of these scaffold materials
      were described. Lyophilized scaffolds obtained from hydrogels were used for cell
      viability experiments, and the results were presented in detail.

PMID- 24728759
TI  - Elevated CO2 and O3 effects on ectomycorrhizal fungal root tip communities in
      consideration of a post-agricultural soil nutrient gradient legacy.
AB  - Despite the critical role of EMF in nutrient and carbon (C) dynamics, combined
      effects of global atmospheric pollutants on ectomycorrhizal fungi (EMF) are
      unclear. Here, we present research on EMF root-level community responses to
      elevated CO2 and O3. We discovered that belowground EMF community richness and
      similarity were both negatively affected by CO2 and O3, but the effects of CO2
      and O3 on EMF communities were contingent on a site soil pH and cation
      availability gradient. These results contrast with our previous work showing a
      strong direct effect of CO2 and O3 on sporocarp community dynamics and
      production. We discuss the possible role of carbon demand and allocation by EMF
      taxa in the discrepancy of these results. EMF communities were structured by a
      legacy of spatially defined soil properties, changing atmospheric chemistry and
      temporal dynamics. It is therefore necessary to understand global change impacts
      across multiple environmental gradients and spatiotemporal scales. 

PMID- 24728761
TI  - Influence of cell disruption and elution on cellulase release of Clostridium
      straminisolvens (CSK1).
AB  - Clostridium straminisolvens (CSK1) is a novel cellulolytic bacterium isolated
      from a cellulose-degrading bacterial community MC1. In this study, the influence
      of the following cell disruption and elution methods on CSK1cellulase release was
      investigated: (1) freezing-thawing, (2) ultrasonication, (3) elution, (4)
      freezing-thawing following elution, (5) ultrasonication following elution, and
      lastly (6) high-pressure homogenization following elution. The activity of the
      cellulases CMCase, beta-glucosidase, Avicelase, FPase, and xylanase in crude
      extracts increased 81.5, 23.8, 87.7, 46.3, and 51.7 %, respectively, with an
      observed optimal treatment method for each cellulase type. The release of protein
      from CSK1 cells increased following either cell disruption or elution and was
      highest at 88.3 % in the homogenization high pressure following elution
      treatment. A newly observed protein was present following cell elution. The
      performance of cell elution as determined by real time-PCR indicated that the
      first time cell elution removed more than 90 % of the CSK1 cells from the
      substrate. These findings demonstrate that cell disruption and elution are
      effective methods for inducing cellulase release, and elution is the key step for
      CSK1. To our knowledge, this study presents the first evidence of optimal
      treatments for induction of cellulase release of Clostridium straminisolvens.
      This information will be of great value for use in subsequent efforts to better
      understand the cellulase characteristics of CSK1 and cellulose degradation
      mechanisms of the MC1 community.

PMID- 24728762
TI  - Preparation, mass diffusion, and biocompatibility analysis of porous-channel
      controlled calcium-alginate-gelatin hybrid microbeads for in vitro culture of
      NSCs.
AB  - The Ca-alginate/gelatin (CAG) microbeads were prepared and evaluated through
      assays for their mechanical strength, permeability, and the feasibility as a cell
      carrier for in vitro culture of neural stem cells. The effects of different
      concentrations of sodium alginate, gelatin, and calcium chloride on the
      mechanical strength of CAG microbeads were determined using a self-made puncture
      force tester. Following this, the microbeads were immersed in DMEM media for a
      specified period to test its decay resistance. A diffusion model including a
      calculation formula of diffusion coefficient was built to investigate the
      diffusion of glucose and bovine serum albumin (BSA) through the wall of the
      microbeads. Furthermore, the feasibility of the microbeads for in vitro culture
      was identified using neural stem cells from Kunming mouse. Through a systematic
      approach and comprehensive analysis, the optimal gelatin conditions for microbead
      preparation were determined; the final combination of parameters of 1.5 % (wt%)
      sodium alginate (SA), 0.5 % (wt%) gelatin, and 4 % (wt%) CaCl2 were the best
      conditions for NSC cultures. This experiment demonstrated that CAG microbeads had
      good cytocompatibility that made it suitable for the culture and successfully
      maintained stemness of neural stem cells. 

PMID- 24728763
TI  - Optimization of xylanase production by filamentous fungi in solid-state
      fermentation and scale-up to horizontal tube bioreactor.
AB  - Five microorganisms, namely Aspergillus niger CECT 2700, A. niger CECT 2915, A.
      niger CECT 2088, Aspergillus terreus CECT 2808, and Rhizopus stolonifer CECT
      2344, were grown on corncob to produce cell wall polysaccharide-degrading
      enzymes, mainly xylanases, by solid-state fermentation (SSF). A. niger CECT 2700
      produced the highest amount of xylanases of 504 +/- 7 U/g dry corncob (dcc) after
      3 days of fermentation. The optimization of the culture broth (5.0 g/L NaNO3, 1.3
      g/L (NH4)2SO4, 4.5 g/L KH2PO4, and 3 g/L yeast extract) and operational
      conditions (5 g of bed loading, using an initial substrate to moistening medium
      of 1:3.6 (w/v)) allowed increasing the predicted maximal xylanase activity up to
      2,452.7 U/g dcc. However, different pretreatments of materials, including
      destarching, autoclaving, microwave, and alkaline treatments, were detrimental.
      Finally, the process was successfully established in a laboratory-scale
      horizontal tube bioreactor, achieving the highest xylanase activity (2,926 U/g
      dcc) at a flow rate of 0.2 L/min. The result showed an overall 5.8-fold increase
      in xylanase activity after optimization of culture media, operational conditions,
      and scale-up. 

PMID- 24728764
TI  - Characterization of a new 1,3-1,4-beta-glucanase gene from Bacillus tequilensis
      CGX5-1.
AB  - 1,3-1,4-beta-Glucanase received great interest due to its application in brewing
      and feed industries. Application of 1,3-1,4-beta-glucanase in brewing industry
      helps make up for the defect that plant-derived beta-glucanases are heat
      sensitive. A new strain, CGX5-1, exhibited remarkable 1,3-1,4-beta-glucanase, was
      isolated from Asian giant hornet nest and identified Bacillus tequilensis.
      Moreover, a new 1,3-1,4-beta-glucanase gene from B. tequilensis was cloned and
      measured to be 720 bp encoding 239 amino acids, with a predicted molecular weight
      of 26.9 kDa. After expressed in Escherichia coli BL21, active recombinant enzyme
      of 24 kDa was detected in the supernatant of cell culture, with the activity of
      2,978.2 U/mL. The new enzyme was stable in the pH 5.0-7.5 with the highest
      activity measured at pH 6.0. Moreover, it is thermostable within 45 to 60 
      degrees C. The property of the new recombinant enzyme makes this enzyme a broad
      prospect in brewing industry. Moreover, this is the first report on 1,3-1,4-beta
      glucanase produced by B. tequilensis. 

PMID- 24728765
TI  - Sequence-specific flexibility organization of splicing flanking sequence and
      prediction of splice sites in the human genome.
AB  - More and more reported results of nucleosome positioning and histone
      modifications showed that DNA structure play a well-established role in splicing.
      In this study, a set of DNA geometric flexibility parameters originated from
      molecular dynamics (MD) simulations were introduced to discuss the structure
      organization around splice sites at the DNA level. The obtained profiles of
      specific flexibility/stiffness around splice sites indicated that the DNA
      physical-geometry deformation could be used as an alternative way to describe the
      splicing junction region. In combination with structural flexibility as
      discriminatory parameter, we developed a hybrid computational model for
      predicting potential splicing sites. And the better prediction performance was
      achieved when the benchmark dataset evaluated. Our results showed that the
      mechanical deformability character of a splice junction is closely correlated
      with both the splice site strength and structural information in its flanking
      sequences. 

PMID- 24728766
TI  - [Trauma and stressor-related disorders: diagnostic conceptualization in DSM-5].
AB  - The Diagnostic and Statistical Manual of Mental Disorders 5 (DSM-5) includes a
      distinct diagnostic group of trauma and stressor-related disorders that has been
      set apart from anxiety disorders. From a perspective of adult psychiatry this new
      disorder category includes posttraumatic stress disorder (PTSD), acute stress
      disorder (ASD), and adjustment disorders. The PTSD is based on narrower trauma
      criteria that focus on acute life-threatening situations, serious injury, or
      sexual violence by way of direct confrontation, witnessing or indirect
      confrontation. Indirect confrontation, however, is reserved only for violent or
      accidental events that occurred to close family members or friends. The former A2
      criterion of an intense emotional reaction to trauma has been removed. A
      deliberately broad approach to clinical PTSD phenomenology has created an
      empirically driven new cluster of persistent negative alterations in cognition
      and mood due to experiencing traumatic events. The ASD has been reconceptualized
      as an intense stress syndrome with a clear need of acute treatment during the
      early course after traumatic exposure. Adjustment disorders continue to emphasize
      maladaptive emotional and behavioral responses to unspecific, non-traumatic
      stressors in an intensity that is beyond social or cultural norms. Neither
      complex PTSD nor prolonged grief disorders have received an independent
      diagnostic status within DSM-5. With respect to stress-related disorders major
      divergences between DSM-5 and the future International Classification of Diseases
      11 (ICD-11) are to be expected. 

PMID- 24728767
TI  - Complex ventral hernia repair with a human acellular dermal matrix.
AB  - PURPOSE: The ideal approach to complex ventral hernia repair is frequently
      debated. Differences in processing techniques among biologic materials may impact
      hernia repair outcomes. This study evaluates the outcomes of hernia repair with a
      terminally sterilized human acellular dermal matrix (TS-HADM) (AlloMax((r))
      Surgical Graft, by C. R. Bard/Davol, Inc., Warwick, RI, USA) treated with low
      dose gamma irradiation. METHODS: A single-arm multi-center retrospective
      observational study of patients undergoing hernia repair with TS-HADM was
      performed. Data analyses were exploratory only; no formal hypothesis testing was
      pre-specified. RESULTS: Seventy-eight patients (43F, 35M) underwent incisional
      hernia repair with a TS-HADM. Mean follow-up was 20.5 months. Preoperative
      characteristics include age of 56.6 +/- 11.1 years, BMI 36.7 +/- 9.9 kg/m(2), and
      mean hernia defect size 187 cm(2). Sixty-five patients underwent component
      separation technique (CST) with a reinforcing graft. Overall, 21.8% developed
      recurrences. Recurrences occurred in 15% of patients repaired with CST. Major
      wound complications occurred in 31% of patients overall. Based upon CDC surgical
      wound classification, major wound complications were seen in 26, 40, 56, and 50%
      of Class 1, 2, 3, and 4 wounds, respectively. No grafts required removal.
      CONCLUSIONS: Hernia recurrences are not uncommon following complex abdominal wall
      reconstruction. Improved outcomes are seen when a TS-HADM is utilized as
      reinforcement to primary fascial closure.

PMID- 24728768
TI  - A rare case of mechanical bowel obstruction caused by mesh plug migration.
AB  - Tension-free hernia repair with a mesh plug is currently one of the most popular
      techniques for open inguinal hernioplasty. It is well tolerated by most patients
      and is associated with few complications. However, rare mesh migration has been
      reported. We describe a case of a 72-year-old man who had undergone inguinal
      hernioplasty with a mesh plug 2 years previously. He visited the emergency
      department complaining of vomiting. Strangulation ileus was suspected, and an
      emergency operation was performed. The mesh plug had migrated into the intra
      peritoneal cavity, granulation tissue had formed around the plug, and the small
      intestine was involved in the granulation tissue. The small intestine was
      strangulated for more than 13 cm, and obstruction was present at this point.

PMID- 24728770
TI  - Temporal bone borehole accuracy for cochlear implantation influenced by drilling
      strategy: an in vitro study.
AB  - PURPOSE: Minimally invasive cochlear implantation is a surgical technique which
      requires drilling a canal from the mastoid surface toward the basal turn of the
      cochlea. The choice of an appropriate drilling strategy is hypothesized to have
      significant influence on the achievable targeting accuracy. Therefore, a method
      is presented to analyze the contribution of the drilling process and drilling
      tool to the targeting error isolated from other error sources. METHODS: The
      experimental setup to evaluate the borehole accuracy comprises a drill handpiece
      attached to a linear slide as well as a highly accurate coordinate measuring
      machine (CMM). Based on the specific requirements of the minimally invasive
      cochlear access, three drilling strategies, mainly characterized by different
      drill tools, are derived. The strategies are evaluated by drilling into synthetic
      temporal bone substitutes containing air-filled cavities to simulate mastoid
      cells. Deviations from the desired drill trajectories are determined based on
      measurements using the CMM. RESULTS: Using the experimental setup, a total of 144
      holes were drilled for accuracy evaluation. Errors resulting from the drilling
      process depend on the specific geometry of the tool as well as the angle at which
      the drill contacts the bone surface. Furthermore, there is a risk of the drill
      bit deflecting due to synthetic mastoid cells. CONCLUSIONS: A single-flute gun
      drill combined with a pilot drill of the same diameter provided the best results
      for simulated minimally invasive cochlear implantation, based on an experimental
      method that may be used for testing further drilling process improvements.

PMID- 24728771
TI  - ACL double bundle linked cortical-aperture tibial fixation: a technical note.
AB  - INTRODUCTION: The purpose of this technical note is to describe the tibial
      fixation characteristics for an all-inside anatomic anterior cruciate ligament
      (ACL) reconstruction method that links extra-cortical button suspensory and
      aperture fixation replicating double bundle soft tissue graft function in single
      femoral and tibial sockets. MATERIALS AND METHODS: A 55 degrees  drill guide
      aligned guidewires in the ACL footprint center of 8 porcine tibiae (mean apparent
      bone mineral density = 1.15 g/cm(2)). A Flipcutter created 27 mm sockets and 15
      mm guidewire channels. Advancement sutures seated porcine soft tissue graft-PEEK
      implants to achieve both socket aperture and extra-cortical button suspensory
      fixation. Potted specimens were loaded into a 6o of freedom clamp with the
      servohydraulic loading vector in direct socket alignment. Constructs were pre
      loaded to 25 N, underwent 10 pre-conditioning cycles (0-50 N, 0.5 Hz), and 500
      submaximal loading cycles (50-250 N, 1 Hz) prior to load to failure testing (20
      mm/min). Mode of failure was recorded. Descriptive statistical analysis was
      performed. RESULTS: All specimens survived the biomechanical test protocol.
      Displacement during cyclic loading was 2.8 +/- 0.9 mm, yield load was 475.2 +/-
      36 N, ultimate load at failure was 671.4 +/- 98 N, stiffness was 127.5 +/- 15
      N/mm. The most common failure mode was suture pulling through the soft tissue
      graft. CONCLUSIONS: This ACL reconstruction method combines the high ultimate
      load to failure and low graft slippage of extra-cortical button suspensory
      fixation with the high stiffness of aperture fixation. Biomechanical test
      findings were comparable or better to previous reports for displacement during
      submaximal loading, ultimate failure load, and construct stiffness. Based on
      current understanding of soft tissue graft ACL reconstruction biomechanics, this
      fixation method should enhance graft-bone socket integration during healing,
      facilitate long-term graft survival, and improve patient outcomes. Clinical
      studies are needed to confirm in vivo efficacy.

PMID- 24728772
TI  - Examining the feasibility and effectiveness of a community-based organization
      implementing an event-based knowledge mobilization initiative to promote physical
      activity guidelines for people with spinal cord injury among support personnel.
AB  - Community-based organizations (CBOs) and support personnel that serve
      marginalized members of society have the potential to be important partners in
      knowledge mobilization (KM). A CBO in partnership with researchers developed an
      event-based KM initiative to disseminate evidence-based physical activity
      guidelines for people with spinal cord injury. PURPOSE: The purpose of this case
      study is to demonstrate a) how a CBO can implement a KM initiative and b) the
      effectiveness of the initiative for disseminating the guidelines to support
      personnel. METHOD: The KM initiative consisted of 12 events about the new
      guidelines held within the CBO's regional areas. Evaluation of the events was
      guided by the RE-AIM (reach, efficacy or effectiveness, adoption, implementation,
      and maintenance) framework. RESULTS: Adoption of the events was high, with 88% of
      regions hosting an event. Overall fidelity to the event protocol was high among
      researchers (100.00% +/- .00), peers (65% +/- 33.74), and staff (70.00% +/-
      34.96). The events reached 140 support personnel who attended the events.
      Significant increases in support personnel's self-efficacy and intentions to
      promote physical activity to people with spinal cord injury were seen at Time 2
      but not maintained at Time 3. CONCLUSIONS: Event-based KM initiatives may be an
      effective strategy for CBOs to disseminate information to support personnel and
      ensure that KM initiatives are supported by staff and delivered as intended.

PMID- 24728773
TI  - Psychological impact of family history risk assessment in primary care: a mixed
      methods study.
AB  - BACKGROUND: Routine family history risk assessment for chronic diseases could
      enable primary care practitioners to efficiently identify at-risk patients and
      promote preventive management strategies. OBJECTIVES: To investigate patients'
      understanding and responses to family history risk assessment in primary care.
      METHOD: A mixed methods study set in 10 Eastern England general practices.
      Participants in a family history questionnaire validation study were triaged into
      population or increased risk for four chronic diseases (type 2 diabetes,
      cardiovascular disease, breast cancer, colorectal cancer). Questionnaires
      completed immediately prior to the family history consultation (baseline) and 4
      weeks later (follow-up) assessed the psychological impact, including State-Trait
      Anxiety Inventory scores. Semi-structured interviews explored the meaning
      participants gave to their personal familial disease risk. RESULTS: Four hundred
      and fifty-three participants completed both baseline and follow-up questionnaires
      and 30 were interviewed. At follow-up, there was no increase in anxiety among
      either group, or differences between the groups [difference in mean change 0.02,
      95% confidence interval -2.04, 2.08, P = 0.98]. There were no significant changes
      over time in self-rated health in either group. At follow-up, participants at
      increased risk (n = 153) were more likely to have recent changes to behaviour and
      they had stronger intentions to make changes to diet (P = 0.001), physical
      activity (P = 0.006) and to seek further information in the future than those at
      population risk (n = 300; P < 0.001). Using qualitative analysis, five themes
      were developed representing ways in which participants gave meaning to familial
      disease risk ('Being reassured', 'Controlling risk', 'Dealing with it later',
      'Beyond my control', 'Disbelieving the risk'). The meanings they attributed to
      increased risk appeared to shape their intention to undertake behaviour change.
      CONCLUSION: Routine assessment for familial risk of chronic diseases may be
      undertaken in primary care without causing anxiety or reducing self-rated health.
      Patient responses to family history risk assessment may inform promotion of
      preventive management strategies.

PMID- 24728774
TI  - Is screening for AF worthwhile? Stroke risk in a screened population from the
      SAFE study.
AB  - INTRODUCTION: Atrial fibrillation (AF) is an important independent risk factor
      for stroke and oral anticoagulation therapy provides a highly effective treatment
      to reduce this risk. Active screening strategies improve detection of AF in
      comparison with routine care; however, whether screen-detected patients have
      stroke risk profiles favouring anticoagulation is unclear. Using data derived
      from the screening for AF in the elderly (SAFE) study, the aim of this article
      was to determine if patients with AF detected via active screening have stroke
      risk profiles that warrant prophylactic anticoagulation. METHODS: Secondary
      analysis of data derived from 25 general practices within which cohorts of 200
      patients were randomly allocated to opportunistic [pulse and electrocardiogram
      (ECG)] or systematic screening (postal invitation for ECG). Stroke risk
      assessment was undertaken using baseline data extracted from medical records and
      CHADS2 criteria. CHADS2 scores were compared between the screening groups.
      RESULTS: One hundred and forty-nine new cases of AF were detected, 75 via
      opportunistic screening and 74 via systematic screening. CHADS2 scores were >=1
      in 83% [95% confidence interval (CI) 72.6-89.6] of patients detected via
      opportunistic screening and 78% (95% CI 67.7-86.2) detected via systematic
      screening. There were no significant differences in stroke risk profiles of
      patients detected via opportunistic and systematic screenings. CONCLUSION: Stroke
      risk profiles of patients detected via opportunistic and systematic screenings
      were similar. Data derived from the SAFE study suggest that active screening for
      AF in patients aged >=65 years in primary care is a useful screening programme
      with 78-83% of patients identified eligible for anticoagulation treatment
      according to the CHADS2 criteria.

PMID- 24728779
TI  - Adjacent segment degeneration and disease after lumbar fusion compared with
      motion-preserving procedures: a meta-analysis.
AB  - PURPOSE: The purpose of our study was to compare lumbar fusion and motion
      preserving procedures to determine whether lumbar fusion may be associated with a
      higher prevalence of adjacent segment degeneration (ASDeg) or adjacent segment
      disease (ASDis). METHODS: We performed a systematic review and meta-analysis for
      articles published up to July 2013. We included randomized controlled trials and
      cohort studies that reported ASDeg or ASDis after lumbar fusion compared with
      motion-preserving devices. Two authors independently extracted the articles and
      the predefined data. RESULTS: A total of 13 studies with 1,270 patients met our
      inclusion criteria and were included in the final analysis. Our analysis showed
      that the prevalence of ASDeg and ASDis, and adjacent segment reoperation rate in
      the fusion group were higher than those in the motion-preserving devices group (P
      < 0.0001, P = 0.0008, and P < 0.0001, respectively). The prevalence of ASDeg and
      reoperation rate in the motion-preserving devices group were significantly lower
      than that in the fusion group for both short- and long-term follow-up (P = 0.0008
      and P = 0.001 at <5 years of follow-up; P = 0.003 and P = 0.001 at >5 years of
      follow-up). CONCLUSIONS: The current evidence suggests that lumbar fusion may
      result in a higher prevalence of adjacent segment degeneration or disease than
      motion-preserving procedures.

PMID- 24728780
TI  - Effectiveness of three types of lumbar orthosis for restricting extension motion.
AB  - Spinal orthoses are implemented to restrict lumbar motion. Several studies have
      compared the effectiveness of various types of lumbar orthoses on restricting
      motion, but none have compared the effect of different back supports on
      restricting extension. This study sought to evaluate the effectiveness of three
      types of lumbar orthosis in regard to their ability to restrict motion during
      extension. Range of motion was quantified using the Spinal Mouse system to
      measure flexion and extension, and the load distribution of the back support was
      measured using a pressure sensor. Ten subjects (8 men, 2 women) were assessed
      under the following five experimental conditions: custom-made stay (CMS),
      aluminum stay (AS), plastic stay (PS), corset only, and no brace. None of the
      stays changed the flexion angle, and none of the supports prevented flexion
      bending. The mean extension angle after immobilization with the CMS, AS, PS,
      corset only, and no brace was 27.5 degrees  +/- 8.5 degrees , 33.4 degrees  +/-
      11.0 degrees , 34.3 degrees  +/- 9.4 degrees , 37.8 degrees  +/- 10.7 degrees ,
      and 42.6 degrees  +/- 10.5 degrees , respectively. The load in the CMS was
      concentrated at the vertical ends of the stay, with a mean load of 11.5 +/- 2.4 N
      at the top and 8.9 +/- 2.4 N at the bottom. The loads at the top and bottom of
      the support were 7.2 +/- 4.3 and 5.3 +/- 3.1 N with the AS and 5.8 +/- 2.3 and
      4.4 +/- 1.7 N with the PS, respectively. All supports allowed similar flexion
      motion. Although the CMS, AS, and PS all restricted extension compared with no
      brace, the CMS was the most effective for restricting trunk extension motion. 

PMID- 24728781
TI  - The hip fracture best practice tariff: early surgery and the implications for
      MRSA screening and antibiotic prophylaxis.
AB  - BACKGROUND: In April 2010, the Department of Health introduced the hip fracture
      best practice. Among the clinical criteria required to earn remuneration is
      surgery within 36 h of admission. However, early surgery may mean that
      methicillin-resistant Staphylococcus aureus (MRSA) colonisation status is not
      known before surgery, and therefore, appropriate antibiotic prophylaxis may not
      be administered. In view of this, our department's policy is to administer an
      additional dose of teicoplanin to patients with unknown MRSA status along with
      routine antimicrobial prophylaxis. AIM: The purpose of this study was to provide
      a safe and effective antimicrobial prophylaxis for hip fracture patients.
      METHODS: We prospectively collected details of demographics and antimicrobial
      prophylaxis for all patients admitted with a hip fracture in November 2011. This
      was repeated in February 2012 after an educational and advertising drive to
      improve compliance with departmental antimicrobial policy. Microbiology results
      were obtained from the hospital microbiology database. A cost-benefit analysis
      was undertaken to assess this regime. RESULTS: A total of 144 hip fracture
      patients were admitted during the 2 months. The average admission to surgery time
      was 32 h, and the average MRSA swab processing time was 35 h. 86 % of patients
      reached theatre with unknown MRSA status. Compliance with the departmental
      antimicrobial policy improved from 25 % in November 2011 to 76 % in February
      2012. Potential savings of L 40,000 were calculated. CONCLUSION: With best
      practice tariff resulting in 86 % of patients reaching theatre with unknown MRSA
      status, we advocate an additional single dose of teicoplanin to cover against
      possible MRSA colonisation.

PMID- 24728782
TI  - Pediatric displaced radial neck fractures: retrospective results of a modified
      Metaizeau technique.
AB  - Treatment of displaced radial neck fractures is challenging and controversial, as
      the risk of unsatisfactory outcome increases after operative as well non
      operative treatment. Between 2004 and 2012, we treated 14 children with type IV
      fracture of radial neck with mean angulation of 72.8 degrees , using the modified
      Metaizeau technique. The average follow-up was 39 months. Heterotrophic
      ossification and transient posterior interosseous nerve palsy were the only
      complication seen in two patients who had to undergo open reduction. We feel that
      the inability to achieve closed reduction can be attributed to loss of periosteal
      hinge. We obtained 100 % excellent clinical outcome and 79 % excellent
      radiological outcome at final follow-up. The modified closed intramedullary pin
      reduction technique proved to be minimal invasive technique for displaced radial
      neck fractures by allowing stable anatomic reconstruction while avoiding all the
      complications of classical Metaizeau technique.

PMID- 24728783
TI  - Influence of the carbon source on Gordonia alkanivorans strain 1B resistance to 2
      hydroxybiphenyl toxicity.
AB  - The viability of bacteria plays a critical role in the enhancement of fossil
      fuels biodesulfurization efficiency since cells are exposed to toxic compounds
      such as 2-hydroxybiphenyl (2-HBP), the end product of dibenzothiophene (DBT)
      biodesulfurization. The goal of this work was to study the influence of the
      carbon source on the resistance of Gordonia alkanivorans strain 1B to 2-HBP. The
      physiological response of this bacterium, pre-grown in glucose or fructose, to 2
      HBP was evaluated using two approaches: a growth inhibition toxicity test and
      flow cytometry. The results obtained from the growth inhibition bioassays showed
      that the carbon source has an influence on the sensitivity of strain 1B growing
      cells to 2-HBP. The highest IC50 value was obtained for the assay using fructose
      as carbon source in both inoculum growth and test medium (IC50-48 h = 0.464 mM).
      Relatively to the evaluation of 2-HBP effect on the physiological state of
      resting cells by flow cytometry, the results showed that concentrations of 2-HBP
      >1 mM generated significant loss of cell viability. The higher the 2-HBP
      concentration, the higher the toxicity effect on cells and the faster the loss of
      cell viability. In overall, the flow cytometry results highlighted that strain 1B
      resting cells grown in glucose-SO4 or glucose-DBT are physiologically less
      resistant to 2-HBP than resting cells grown in fructose-SO4 or fructose-DBT,
      respectively. 

PMID- 24728784
TI  - Metabolomics coupled with pattern recognition and pathway analysis on potential
      biomarkers in liver injury and hepatoprotective effects of yinchenhao.
AB  - Metabolomics can provide an opportunity to develop the systematic analysis of the
      metabolites in biological samples and has been increasingly applied to
      discovering and identifying biomarkers and perturbed pathways. It enables us to
      better understand the metabolic pathways which can clarify the mechanism of
      traditional Chinese medicines (TCM). Yinchenhao (YCH, Artemisia annua L), a
      famous TCM plant, has been used clinically for more than a thousand years to
      relieve liver diseases in Asia, and its mechanisms are not still completely
      clear. Here, metabolomic techniques may provide additional insight, and our
      investigation was designed to assess the effects and possible mechanisms of YCH
      on alpha-naphthylisothiocyanate (ANIT)-induced liver injury. Metabolite profiling
      was performed by ultra-performance liquid chromatography/electrospray ionization
      quadruple time-of-flight mass spectrometry (UPLC/ESI-Q-TOF/MS) combined with
      pathway analysis and pattern recognition approaches including independent
      component analysis (ICA) and partial least squares-discriminant analysis (PLS
      DA). Biochemistry test was also performed for the liver tissue and plasma
      samples. The changes in metabolic profiling were restored to their baseline
      values after YCH treatment according to the ICA score plots. Of note, YCH has a
      potential pharmacological effect through regulating multiple perturbed pathways
      to normal state, correlating well to the assessment of biochemistry test. Five
      different potential biomarkers in the positive mode contributing to the treatment
      of YCH were discovered. Pathway analysis showed that these metabolites were
      associated with perturbations in pyrimidine metabolism, primary bile acid
      biosynthesis, and propanoate metabolism, which may be helpful to further
      understand the action mechanisms of YCH. It showed that changed biomarkers and
      pathways may provide evidence to insight into drug action mechanisms and drug
      discovery. 

PMID- 24728785
TI  - The role of radiotherapy in the management of progressive glioblastoma : a
      systematic review and evidence-based clinical practice guideline.
AB  - QUESTION: Can re-irradiation (by using conventional radiotherapy, fractionated
      radiosurgery, or single fraction radiosurgery) be used in patients with
      progressive glioblastoma multiforme after the first adjuvant combined
      multimodality treatment with radiation and chemotherapy? TARGET POPULATION: These
      recommendations apply to adult patients with progressive glioblastoma after first
      line combined multimodality treatment with chemotherapy and radiation.
      RECOMMENDATIONS  LEVEL III: When the target tumor is amenable for additional
      radiation, re-irradiation is recommended as it provides improved local tumor
      control, as measured by best imaging response. Such re-irradiation can take the
      form of conventional fractionation radiotherapy, fractionated radiosurgery, or
      single fraction radiosurgery. LEVEL III: Re-irradiation is recommended in order
      to maintain or improve a patient's neurological status and quality of life prior
      to any further tumor progression.

PMID- 24728786
TI  - Occult radiological effects of lipomatosis of the lumbosacral plexus.
AB  - OBJECTIVE: Lipomatosis of nerve (LN) is a condition of massive peripheral nerve
      enlargement frequently associated with hypertrophy within the distribution of the
      nerve, and most commonly affecting the distal limbs. We sought to understand if
      LN of the lumbosacral plexus would be associated with the trophic effects of LN
      on surrounding tissue within the pelvis, which may be clinically occult, but
      present on MRI. MATERIALS AND METHODS: Fifty-one cases of LN, confirmed by
      pathology or pathognomonic appearance on MRI, were reviewed. Patients with LN of
      the sciatic nerve were investigated for radiological signs suggestive of
      overgrowth. RESULTS: Five patients had involvement of the sciatic nerve, 4 of
      whom had MR imaging of the pelvis. Three patients had LN involving the
      lumbosacral plexus, and one patient had isolated involvement of the sciatic
      nerve. All patients with involvement of the lumbosacral plexus demonstrated
      previously unrecognized evidence of nerve territory overgrowth in the pelvis,
      including: LN, profound adipose proliferation, muscle atrophy and fatty
      infiltration, and bone hypertrophy and ankylosis. The patient with LN involving
      the intrapelvic sciatic nerve, but not the lumbosacral plexus did not demonstrate
      any radiological evidence of pelvic overgrowth. CONCLUSION: LN is broader in
      anatomical reach than previously understood. Proximal plexal innervation may be
      involved, with a consequent effect on axial skeleton and intrapelvic structures.

PMID- 24728789
TI  - Cementless total hip arthroplasty with BiCONTACT stem - go od results at long
      term of follow -up.
AB  - BACKGROUND: The aim of our study was an evaluation of long-term clinical and
      radiological results of arthroplasty with BiCONTACT stem. MATERIAL AND METHODS:
      We qualified 115 patients (125 hips) to the retrospective analysis with a minimum
      10-year follow-up period. The mean age of patients on the day of surgery varied
      was 50.7 years. The follow-up period lasted from 126 to 199 months (mean 14
      years). RESULTS: Harris hip score increased from 47.1 before operations to 85.3
      at the last follow-up. Excellent results were recorded in 81 (64.8%) cases, good
      results in 23 (18.4%) and satisfactory results in 10 (8%) cases, while failure
      was noted in 11 cases. In 2 cases, aseptic stem loosening was identified, in 8
      cup and in 2 cases both: cup and stem loosening. The BiCONTACT stem survival,
      assessed with the Kaplan-Meier estimator was 97.6%, while that of the both: cup
      and stem amounted to 91.2%, having taken into account acetabulum or stem
      loosening as end-point, regardless of cause. CONCLUSIONS: 1. In an average 14
      year observations, application of a BiCONTACT stem gives good clinical results.
      2. With no incidental complications and proper operative technique, the risk of
      aseptic loosening is really scarce.

PMID- 24728790
TI  - Success rates for initial eradication of peri-prosthetic knee infection treated
      with a two-stage procedure.
AB  - BACKGROUND: In Germany, rates of primary total knee arthroplasty procedures and
      exchange arthroplasty procedures continue to rise. Late-onset peri-prosthetic
      infection constitutes a serious complication whose management may be dependent
      upon the spectrum of micro-organisms involved. The aim of this study was to
      provide a retrospective analysis of the effectiveness of initial eradication
      measures performed as part of a two-stage procedure. MATERIAL AND METHODS:
      Between 2002 and 2008, a total of 328 patients who had received a first-time
      diagnosis of chronic peri-prosthetic knee infection following total knee
      arthroplasty (TKA) subsequently underwent surgery at our clinic. The surgical
      approach consisted of a two-stage procedure, with the initial procedure
      consisting of the removal of the prosthesis and radical debridement, followed by
      insertion of an antibiotic-loaded static spacer. The effectiveness of the
      procedure was assessed after six weeks, with each patient undergoing a number of
      clinical and laboratory-based tests, including knee joint aspiration. RESULTS:
      Staphylococcus aureus strains were responsible for 68% (n=223) of the total
      number of cases of peri-prosthetic knee infection. 19% of cases (n=62) showed
      evidence of gram-negative bacteria, while MRSA accounted for 15% (n=49) of cases.
      Six weeks after completion of the above-named treatment regimen, eradication of
      infection was considered successful in 289 patients (88.1%). Eradication was
      unsuccessful in 22% of MRSA infections (n=11) and 7% of MSSA infections (n=23).
      CONCLUSION: The treatment regimen outlined in this report is capable of achieving
      satisfactory results in the management of late-onset peri-prosthetic knee
      infection, with one exception: patients with infections caused by MRSA showed
      high failure rates.

PMID- 24728791
TI  - Clinical usefulness of the Staffelstein-Score in the functional assessment in
      knee arthroplasty patients.
AB  - BACKGROUND: The aim of the study was to compare the authors' own modification of
      the Staffelstein-Score against the HSS Knee Score in the assessment of early
      results of knee arthroplasty. MATERIAL AND METHODS: A total of 67 patients
      qualified for knee arthroplasty (average age 68.5 years) were examined. 62
      patients underwent a surgical procedure. A control group comprised 74 healthy
      patients (average age 67.5 years). Muscle strength and knee range of motion were
      measured and HSS Knee Score (HSS) and modified Staffelstein-Score (MSS)
      assessments were performed. The experimental group was assessed at baseline (Test
      1) and at 8 (Test 2) and 100 (Test 3) days postoperatively. The control group was
      examined once. RESULTS: The Staffelstein-Scores on successive examinations were
      67, 59 and 100 pts in the experimental group and 119 pts in the control group.
      Statistically significant differences were noted between the results within the
      experimental group and between the groups. The respective HSS Knee Score results
      were 46, 44 and 73 pts in the experimental group and 96 pts in the control group.
      Statistically significant differences were observed as regards the results,
      except the baseline assessment vs. Test 2. CONCLUSIONS: 1. The sensitivity of the
      HSS Knee Score is insufficient if tests are carried out at short intervals. It
      does not provide a balanced assessment of the functional capability and clinical
      performance of the joint. 2. The modified Staffelstein-Score has a high
      sensitivity to clinical changes, even those occurring a few days following an
      arthroplasty procedure. 3. The MSS is also useful as a balanced assessment of
      pain, joint functional capability and clinical examination results.

PMID- 24728792
TI  - Results of two-stage operative treatment of anteromedial instability of the knee.
AB  - BACKGROUND: Proper treatment of massive knee injuries still constitutes a
      challenge for clinicians. Most often a torsion knee injury results in a rupture
      of the medial collateral ligament and anterior cruciate ligament. There is still
      no consensus on whether total rupture (Grade III) of the medial collateral
      ligament requires surgery, but it is well known that anterior cruciate ligament
      injury will require reconstructive surgery. MATERIAL AND METHODS: A total of 27
      patients treated with two-staged surgery (primary MCL repair and delayed ACL
      reconstruction) were enrolled. Treatment outcomes were evaluated using the IKDC
      scale and Lysholm scale. The range of motion and knee stability was assessed
      during a clinical examination. Radiographs were used to evaluate the placement of
      suture anchors and development of osteoarthritic lesions. Static and dynamic
      ultrasound examinations were also performed to assess the post-operative
      morphology and performance of the medial collateral ligament. RESULTS: The
      patients who had undergone surgery for combined anteromedial instability of the
      knee, achieved good or very good clinical outcome according to the IKDC scale
      (63%, 17 of 27) and the Lysholm scale (74%, 20 of 27). Unsatisfactory functional
      outcomes were more often seen in older patients. Some patients developed
      complications, which significantly worsened the outcome. Those mainly included a
      limited range of movement, arthrofibrosis and Pellegrini-Stieda lesions.
      CONCLUSIONS: 1.Two-stage operative treatment produces good or very good results
      in most patients. Nevertheless, there is a risk of complications in some cases,
      mostly in patients aged 40 years. Accordingly, two-stage treatment is currently
      recommended in younger individuals. 2. A complete MCL tear at the distal
      attachment should be given particular attention. Although such injury is rare,
      due to the anatomical determinants and the risk of Stener-like lesions, i.e.
      unhealed ML, surgery is recommended. Surgery produces good clinical and
      functional results.

PMID- 24728793
TI  - Effectiveness of physiotherapy in the treatment of excessive lateral pressure
      syndrome after anterior cruciate ligament reconstruction - preliminary report.
AB  - BACKGROUND: The excessive lateral pressure syndrome is a common complication
      following anterior cruciate ligament (ACL) reconstruction is. It may lead to
      premature wear of the articular surfaces of the femur and patella. The aim of the
      study was to assess the effectiveness of physiotherapy in the treatment of
      excessive lateral pressure syndrome after ACL reconstruction. MATERIAL AND
      METHODS: A total of 18 patients (4 women, 14 men) after arthroscopic ACL
      reconstruction were enrolled (age: 16 -54 years). The patients were randomly
      divided into two groups: experimental (Group E, 9 people), who attended therapy,
      and control (group C, 9 people). The distance between the lateral edge of the
      patella and the lateral condyle of femur was measured with an ultrasound scanner
      in both extremities. The experimental group patients attended 12 treatment
      sessions of the.Neurac method. A single session lasted 45 minutes. RESULTS: The
      baseline examination of both groups showed statistically significant excessive
      lateral pressure in the operated extremity in relation to the non-operated one in
      every angular position. At the same time, the quadriceps femoris of the operated
      extremity was found to be significantly weaker than its counterpart. On
      completion of the rehabilitation, statistically significant differences in
      quadriceps strength were recorded in the experimental group compared to the
      baseline examination while there were no significant differences in the control
      group. An intergroup comparison did not reveal any significant differences in
      quadriceps strength. There were also no significant differences in the severity
      of lateral pressure syndrome before and after the therapy in either group.
      CONCLUSIONS: 1. Rehabilitation improved quadriceps femoris, strength; it did not,
      however, decrease excessive lateral pressure syndrome. 2. The rehabilitation
      programme is not sufficient in conservative treatment of excessive lateral
      pressure syndrome.

PMID- 24728794
TI  - The effect of migration of instantaneous centre of knee orthosis rotation during
      gait - in vivo displacement measurements in two experimental variants.
AB  - BACKGROUND: The knee joint is a bicondylar hinge two-level joint with six degrees
      of freedom. The location of the functional axis of flexion-extension motion is
      still a subject of research and discussions. During the swing phase, the femoral
      condyles do not have direct contact with the tibial articular surfaces and the
      intra-articular space narrows with increasing weight bearing. The geometry of
      knee movements is determined by the shape of articular surfaces. MATERIAL AND
      METHODS: A digital recording of the gait of a healthy volunteer was analysed. In
      the first experimental variant, the subject was wearing a knee orthosis
      controlling flexion and extension with a hinge-type single-axis joint. In the
      second variant, the examination involved a hinge-type double-axis orthosis.
      Statistical analysis involved mathematically calculated values of displacement P.
      Scatter graphs with a fourth-order polynomial trend line with a confidence
      interval of 0.95 due to noise were prepared for each experimental variant.
      RESULTS: In Variant 1, the average displacement was 15.1 mm, the number of tests
      was 43, standard deviation was 8.761, and the confidence interval was 2.2. The
      maximum value of displacement was 30.9 mm and the minimum value was 0.7 mm. In
      Variant 2, the average displacement was 13.4 mm, the number of tests was 44,
      standard deviation was 7.275, and the confidence interval was 1.8. The maximum
      value of displacement was 30.2 mm and the minimum value was 3.4 mm. An analysis
      of moving averages for both experimental variants revealed that displacement
      trends for both types of orthosis were compatible from the mid-stance to the mid
      swing phase. CONCLUSIONS: 1. The method employed in the experiment allows for
      determining the alignment between the axis of the knee joint and that of shin and
      thigh orthoses. 2. Migration of the single and double-axis orthoses during the
      gait cycle exceeded 3 cm. 3. During weight bearing, the double-axis orthosis was
      positioned more correctly. 4. The study results may be helpful in designing new
      hinge-type knee joints.

PMID- 24728795
TI  - Pathological fracture in osteosarcoma: is it always an indication for amputation?
AB  - BACKGROUND: The presence of a pathological fracture due to osteosarcoma (OS) has
      been considered a high risk factor for dissemination and an indication for
      immediate amputation. With current neoadjuvant chemotherapy regimens there is a
      trend towards limb salvage procedures in selected cases. The aim of this study is
      to assess the outcome of patients treated with amputation versus patients treated
      with limb salvage surgery focusing on local recurrence, mortality rates and
      metastatic dissemination. MATERIAL AND METHODS: A retrospective study of patients
      with OS treated at our institution was performed. Fifteen patients with a mean
      age of 25.6 years (8 to 66) were identified with an average follow up of 7 years
      (2 to 29). Patients were treated either with amputation (8) or limb salvage
      procedure (6). One patient was not treated surgically. RESULTS: Four patients
      developed local recurrence (1 in the amputation group and 3 in the limb salvage
      group, treated with secondary amputation). Six patients developed pulmonary
      metastasis (4 in the amputation group and 2 in the limb salvage) and 3 patients
      died (all of them in the amputation group). CONCLUSIONS: 1. A pathologic fracture
      in an OS is not always a contraindication for limb salvage because the oncologic
      results are acceptable. 2. In selected cases limb salvage has similar success
      rates to amputation.

PMID- 24728796
TI  - Post irradiation myelopathy: from the physiatrists' point of view.
AB  - We describe two patients who developed a severe spinal cord damage long time
      after cessation of irradiation therapy. The various and unique rehabilitation
      medicine aspects are discussed and the literature is surveyed. 

PMID- 24728797
TI  - Osteochondrosis of the capitellum of the humerus (Panner's disease,
      Osteochondritis Dissecans). Case study.
AB  - The article presents a case of an adolescent patient suffering from
      osteochondritis of the humeral capitellum. Early symptoms of this disease
      appeared at an age typically associated with the onset of both Panner's disease
      and Osteochondritis Dissecans (OCD) of the humeral capitellum. About two years
      after the onset of the early symptoms, the patient reported to a specialised
      clinic. He was followed up for almost two years and was hospitalised and
      underwent surgical treatment during that period. Both diseases bear multiple
      similarities, which may entail diagnostic errors. The paper presents differences
      between these two similar clinical entities, in particular in terms of treatment
      and prognosis. Essential details potentially allowing for early diagnosis and
      classification of both conditions are described and discussed. Resolving the
      discussion may significantly contribute to improving performance and quality of
      life of patients suffering from necrosis of the humeral capitellum. 

PMID- 24728798
TI  - Assessment of strength & velocity parameters of hip joint muscles in
      rehabilitation of a patient with lower limb amelia. Case study.
AB  - We studied a 19-year-old patient with congenital partial absence of certain left
      lower limb structures (amelia) with no additional developmental defects. The
      patient had no fibula or foot bones and the tibia was reduced to 3 cm, which made
      it impossible to use a crural prosthesis. The aim of the study was to assess the
      strength capacity of muscles influencing the ipsi- and contralateral hip joint in
      the amelic patient. Compared to healthy individuals, patients with a congenital
      absence of lower limb demonstrate a marked disproportion in muscle peak torque
      between hip flexors and hip extensors, which may lead to damage to the weaker
      muscle group. The disproportions may be reduced with a rehabilitation programme
      aimed to strengthen the hip joint extensors. 

PMID- 24728799
TI  - [Not Available].

PMID- 24728800
TI  - Molecularly targeting the PI3K-Akt-mTOR pathway can sensitize cancer cells to
      radiotherapy and chemotherapy.
AB  - Radiotherapy and chemotherapeutic agents that damage DNA are the current major
      non-surgical means of treating cancer. However, many patients develop resistances
      to chemotherapy drugs in their later lives. The PI3K and Ras signaling pathways
      are deregulated in most cancers, so molecularly targeting PI3K-Akt or Ras-MAPK
      signaling sensitizes many cancer types to radiotherapy and chemotherapy, but the
      underlying molecular mechanisms have yet to be determined. During the multi-step
      processes of tumorigenesis, cancer cells gain the capability to disrupt the cell
      cycle checkpoint and increase the activity of CDK4/6 by disrupting the PI3K, Ras,
      p53, and Rb signaling circuits. Recent advances have demonstrated that PI3K-Akt
      mTOR signaling controls FANCD2 and ribonucleotide reductase (RNR). FANCD2 plays
      an important role in the resistance of cells to DNA damage agents and the
      activation of DNA damage checkpoints, while RNR is critical for the completion of
      DNA replication and repair in response to DNA damage and replication stress.
      Regulation of FANCD2 and RNR suggests that cancer cells depend on PI3K-Akt-mTOR
      signaling for survival in response to DNA damage, indicating that the PI3K
      AktmTOR pathway promotes resistance to chemotherapy and radiotherapy by enhancing
      DNA damage repair.

PMID- 24728815
TI  - Pet ownership among homeless youth: associations with mental health, service
      utilization and housing status.
AB  - As many as 25 % of homeless persons have pets. To our knowledge, pet ownership
      has not been studied quantitatively with homeless youth. This study examined pet
      ownership among 398 homeless youth utilizing two Los Angeles drop-in centers.
      Twenty-three percent of homeless youth had a pet. The majority of pet owners
      reported that their pets kept them company and made them feel loved; nearly half
      reported that their pets made it more difficult to stay in a shelter. Pet owners
      reported fewer symptoms of depression and loneliness than their non-pet owning
      peers. Pet ownership was associated with decreased utilization of housing and job
      finding services, and decreased likelihood of currently staying in a shelter.
      These findings elucidate many of the positive benefits of pet ownership for
      homeless youth, but importantly highlight that pet ownership may negatively
      impact housing options. Housing and other services must be sensitive to the needs
      of homeless youth with pets. 

PMID- 24728816
TI  - Predictive factors for extended-spectrum beta-lactamase producing
      Enterobacteriaceae causing infection among intensive care unit patients with
      prior colonization.
AB  - We investigated the predictive factors for extended-spectrum beta-lactamase
      producing Enterobacteriaceae (ESBL-PE) causing infections among intensive care
      unit patients with prior documented ESBL-PE colonization. Using multivariate
      analysis, referral from medical ward, nursing home or rehabilitation center [Odds
      ratio (OR), 2.5; 95 % confidence interval (CI), [1.3-5.0]; p = 0.007], previous
      fluoroquinolone treatment (OR, 3.4; CI, [1.1-10.5]; p = 0.003), extracorporeal
      membrane oxygenation (OR, 4.6; CI, [1.3-15.9]; p = 0.02), and absence of prior
      positive ESBL-PE rectal swab culture (OR, 5.0; CI, [1.6-10.0]; p = 0.0009) were
      risk factors for ESBL-PE infection. Easily identifiable factors may help with
      targeting carbapenem prescriptions.

PMID- 24728817
TI  - Effects of a novel proteasome inhibitor BU-32 on multiple myeloma cells.
AB  - Proteasome inhibition is associated with substantial antitumor effects in
      preclinical models of multiple myeloma (MM) as well as in patients. However,
      results of recent clinical trials to evaluate the effect of the proteasome
      inhibitor Bortezomib (Velcade((r)), also called PS-341) in MM patients have shown
      limited activity when used as a single agent. This underscores the need to find
      new efficacious and less toxic proteasome inhibitors. Recently, carfilzomib was
      approved for the treatment of refractory/relapsed MM and several new agents have
      been introduced into the clinic, including marizomib and MLN9708, and trials
      investigating these second-generation proteasome inhibitors have demonstrated
      promising results. We have recently synthesized a novel proteasome inhibitor, BU
      32, and tested its growth inhibitory effects in different human MM cells
      including RPMI8226, MM.1S, MM.1R, and U266. In this study, we evaluate the
      efficacy of the novel proteasome inhibitor BU-32 (NSC D750499) using an in vitro
      MM model. BU-32 exhibits strong cytotoxicity in a panel of MM cell lines-
      RPMI8226, MM1S, MM1R, and U266. In addition, we demonstrate by proteasome
      inhibition assay that BU-32 potently inhibits the chymotryptic- and caspase-like
      activities of the 26S proteasome. We further show from Annexin V-FITC binding
      studies that BU-32, like Bortezomib, induces apoptosis in a panel of MM cell
      lines but the effect is more pronounced with BU-32-treated cells. Invasion assay
      with the MM.1S cell line indicates that BU-32 inhibits the invasiveness of
      myeloma cells. Results from our studies using real-time PCR array analyses show
      that BU-32 effectively downregulates an array of angiogenesis and inflammatory
      markers. Our results suggest that BU-32 might be a potential chemotherapeutic
      agent with promising antitumor activity for the treatment of MM.

PMID- 24728818
TI  - Delivering optimal care for inflammatory bowel disease patients in Scotland in
      2014.
AB  - The inflammatory bowel diseases (IBDs), Crohn's disease and ulcerative colitis,
      present an ever increasing burden to the healthcare systems in the Western world.
      Scotland in particular has seen a significant increase in both diseases,
      particularly Crohn's disease. It is thus of paramount importance that secondary
      care services within Scotland are equipped to cope with this increased demand at
      a time when the treatment options are broadening, patients expectations are
      increasing and healthcare budgets face major restriction. This article outlines
      some aspects of optimal delivery of an IBD service in secondary care. 

PMID- 24728819
TI  - Optimal approach to circumferential decompression and reconstruction for thoracic
      spine metastatic disease.
AB  - BACKGROUND: Circumferential decompression has been demonstrated to be the first
      line therapy for patients with metastatic tumors in the thoracic spine requiring
      surgical intervention. However, there is significant debate regarding whether
      these tumors are best accessed anteriorly utilizing a thoracotomy or posteriorly.
      We used decision analysis to determine which approach yields greater health
      related quality of life (QOL). METHODS: We searched Medline, Embase, and the
      Cochrane Library for relevant articles published between 1990 and 2011 on
      anterior and posterior approaches to metastatic disease in the thoracic spine.
      QOL values for major treatment outcomes were determined using the existing
      literature. Separate models were created for ambulatory and nonambulatory
      patients. A Monte Carlo simulation and sensitivity analyses were used to
      determine which treatment strategy resulted in the highest QOL. RESULTS: For
      ambulatory patients, an anterior approach resulted in a slightly higher QOL, and
      for nonambulatory patients, a posterior approach was favored, but these
      differences were not statistically significant. CONCLUSIONS: Using a decision
      analytic model, we found no significant difference in QOL resulting from anterior
      versus posterior approaches to metastatic lesions in the thoracic spine.
      Decisions should instead be based on surgeon comfort, tumor characteristics,
      anatomy of the lesion, patient-related factors, and goals of the operation.

PMID- 24728820
TI  - The usefulness of neoadjuvant chemoradiation therapy for locally advanced
      esophageal cancer with multiple lymph-node metastases.
AB  - BACKGROUND: The prognosis of patients with esophageal squamous-cell cancer (ESCC)
      and multiple lymph-node metastases is quite poor. We examined whether neoadjuvant
      chemoradiation therapy (CRT) has a beneficial effect in such patients. METHODS: A
      total of 50 consecutive patients with T3-4 tumors and without organ metastases
      were prospectively enrolled. Of those patients, 20, who had four or more nodal
      metastases, underwent neoadjuvant CRT (CRT group), and the remaining 30 patients,
      who had three or fewer nodal metastases, underwent surgery alone (surgery group).
      CRT consisted of 5-fluorouracil plus cisplatin and 40 Gy of radiation. The
      groups' clinical outcomes were compared. RESULTS: Surgery was performed in 48
      patients: all enrolled patients except for 2 who had organ metastasis after CRT.
      In the CRT group, the number of patients with pathological complete response was
      observed in 8 patients (44 %), mean nodal metastases number was changed from 8.2
      to 2.6 and 9 patients had pN0. The 3-year survival rate was 76 % in the CRT group
      (4 patients relapsed) and 68 % in the surgery group (8 patients relapsed), which
      is not a statistically significant difference (P = 0.61). CONCLUSIONS:
      Neoadjuvant CRT is beneficial for locally advanced ESCC with four or more lymph
      node metastases.

PMID- 24728821
TI  - Should patients being considered for surgical management in melanoma centers have
      their histology reviewed by specialized pathologists?

PMID- 24728822
TI  - Evaluation of the nodal status in the 7th edition of the UICC-TNM classification
      for esophageal squamous cell carcinoma: proposed modifications for improved
      survival stratification : impact of lymph node metastases on overall survival
      after esophagectomy.
AB  - BACKGROUND: The 7th edition of the Union for International Cancer Control-TNM
      (UICC-TNM) classification for esophageal carcinoma made considerable
      modifications to the definition of N-staging by the number of involved lymph
      nodes and the regional node boundary. There were few validations of the regional
      boundary. We evaluated the nodal status of this classification for esophageal
      squamous cell carcinoma (ESCC). METHODS: There were 665 patients reviewed who had
      ESCC and underwent esophagectomy between 1997 and 2012. We evaluated the impact
      of the location of lymph node metastasis on overall survival. RESULTS: There were
      414 patients (61.7 %) who had lymph node metastases. The overall 5-year survival
      rate was 54.7 %. There were no significant differences in survival among N2, N3,
      and M1 patients. Cox regression analysis revealed that common hepatic or splenic
      node involvements (P = 0.001), pT stage (P = 0.0002), and pN stage (P < 0.0001)
      were independent predictors of survival, but supraclavicular node involvement (P
      = 0.29) was not. We propose a modified nodal status that designates
      supraclavicular node as regional: m-N0 (5-year survival = 79 %; n = 251); m-N1 (5
      year = 56 %; n = 212); m-N2 (5-year = 30 %; n = 114); m-N3 (5-year = 18 %; n =
      52); m-M1 (5-year = 6.2 %; n = 36). This modified nodal staging predicts survival
      better than the current staging system. CONCLUSIONS: The modification of
      supraclavicular lymph node from nonregional to regional in the 7th UICC
      classification of ESCC may allow for better stratification of overall survival.

PMID- 24728823
TI  - Minimum nodal yield in oral squamous cell carcinoma: defining the standard of
      care in a multicenter international pooled validation study.
AB  - PURPOSE: There is evidence to suggest that a nodal yield <18 is an independent
      prognostic factor in patients with clinically node negative (cN0) oral squamous
      cell carcinoma (SCC) treated with elective neck dissection (END). We sought to
      evaluate this hypothesis with external validation and to investigate for
      heterogeneity between institutions. PATIENTS AND METHODS: We analyzed pooled
      individual data from 1,567 patients treated at nine comprehensive cancer centers
      worldwide between 1970 and 2011. Nodal yield was assessed with Cox proportional
      hazard models, stratified by study center, and adjusted for age, sex,
      pathological T and N stage, margin status, extracapsular nodal spread, time
      period of primary treatment, and adjuvant therapy. Two-stage random-effects meta
      analyses were used to investigate for heterogeneity between institutions.
      RESULTS: In multivariable analyses of patients undergoing selective neck
      dissection, nodal yield <18 was associated with reduced overall survival [hazard
      ratio (HR) 1.69; 95 % confidence interval (CI) 1.22-2.34; p = 0.002] and disease
      specific survival (HR 1.88; 95 % CI 1.21-2.91; p = 0.005), and increased risk of
      locoregional recurrence (HR 1.53; 95 % CI 1.04-2.26; p = 0.032). Despite
      significant differences between institutions in terms of patient
      clinicopathological factors, nodal yield, and outcomes, random-effects meta
      analysis demonstrated no evidence of heterogeneity between centers in regards to
      the impact of nodal yield on disease-specific survival (p = 0.663; I (2)
      statistic = 0). CONCLUSION: Our data confirm that nodal yield is a robust
      independent prognostic factor in patients undergoing END for cN0 oral SCC, and
      may be applied irrespective of the underlying patient population and treating
      institution. A minimum adequate lymphadenectomy in this setting should include at
      least 18 nodes.

PMID- 24728824
TI  - Laparoscopic colectomy decreases the time to administration of chemotherapy
      compared with open colectomy.
AB  - BACKGROUND: Minimally invasive colon surgery (MIS) has been shown to minimize
      pain and decrease overall recovery time. No studies have shown a clear oncologic
      benefit. Some literature suggests that the time to administration of chemotherapy
      can be important to improve outcomes for advanced colon cancer. The goal of this
      study is to evaluate the effect of minimally invasive surgery on the timing of
      chemotherapy administration. METHODS: This was a retrospective review of all
      patients undergoing surgery for colon cancer at a tertiary institution between
      2004 and 2013. RESULTS: A total of 668 partial colectomies for cancer were
      performed; 241 were stage III and above and deemed appropriate for chemotherapy.
      Eighty-five patients did not receive chemotherapy (patient's wishes,
      age/comorbidities or lost to follow-up). Of the 156 patients who received
      chemotherapy, 57 underwent MIS and 99 had open colectomy. Average time to
      chemotherapy after MIS colectomy was 42.9 versus 60.3 days for open surgery (p <
      0.001). In the open group, 52 (53 %) people had postoperative complications and
      readmissions versus 24 (39 %) in the MIS group. Postoperative complications
      increased the time to chemotherapy for all patients. However, among patients with
      complications, patients in the MIS group were still able to start chemotherapy
      earlier (p < 0.05) than open colectomy patients. Multivariate analysis revealed
      the MIS approach as the only factor lowering time between surgery and
      chemotherapy. CONCLUSIONS: Laparoscopic colectomy decreases the time interval
      from surgery to the start of chemotherapy compared with open colectomy.
      Postoperative complications increase the time to chemotherapy for both open and
      MIS surgery.

PMID- 24728827
TI  - Treatment with low-temperature atmospheric pressure plasma enhances cutaneous
      delivery of epidermal growth factor by regulating E-cadherin-mediated cell
      junctions.
AB  - The barrier system of the skin not only defends against antigens and harmful
      substances, but also hinders the permeation of medicines and cosmetics into the
      dermis. Several strategies have been developed to enhance the absorption ability
      of skin, including the use of chemicals and skin ablation devices. However, the
      cost and inconvenience of these strategies highlights the need for a novel and
      safe method for increasing skin absorption. In this study, we examined the effect
      of low temperature atmospheric pressure plasma (LTAPP) on the efficiency of drug
      penetration through the skin, as well as its mechanism of action. HaCaT human
      keratinocytes and hairless mice were exposed to LTAPP treatment, and the cellular
      and tissue gene expression, and morphological changes were monitored. We found
      that the LTAPP exposure reduced the expression of E-cadherin in skin cells and
      led to the loss of cell-cell contacts. The exposure of mouse skin to LTAPP also
      reduced the expression of E-cadherin and prevented intercellular junction
      formation within the tissue, leading to enhanced absorption of hydrophilic
      agents, eosin and epidermal growth factor. The reduction in E-cadherin expression
      and reduced skin barrier function recovered completely within 3 h of LTAPP
      exposure. Taken together, these data show that LTAPP can induce a temporal
      decrease in the skin barrier function by regulating E-cadherin-mediated
      intercellular interactions, leading to the enhanced transdermal delivery of drugs
      and cosmetics. 

PMID- 24728830
TI  - Interactions among mitochondrial proteins altered in glioblastoma.
AB  - Mitochondrial dysfunction is putatively central to glioblastoma (GBM)
      pathophysiology but there has been no systematic analysis in GBM of the proteins
      which are integral to mitochondrial function. Alterations in proteins in
      mitochondrial enriched fractions from patients with GBM were defined with label
      free liquid chromatography mass spectrometry. 256 mitochondrially-associated
      proteins were identified in mitochondrial enriched fractions and 117 of these
      mitochondrial proteins were markedly (fold-change >= 2) and significantly altered
      in GBM (p <= 0.05). Proteins associated with oxidative damage (including
      catalase, superoxide dismutase 2, peroxiredoxin 1 and peroxiredoxin 4) were
      increased in GBM. Protein-protein interaction analysis highlighted a reduction in
      multiple proteins coupled to energy metabolism (in particular respiratory chain
      proteins, including 23 complex-I proteins). Qualitative ultrastructural analysis
      in GBM with electron microscopy showed a notably higher prevalence of
      mitochondria with cristolysis in GBM. This study highlights the complex
      mitochondrial proteomic adjustments which occur in GBM pathophysiology.

PMID- 24728831
TI  - Vorinostat as a radiosensitizer for brain metastasis: a phase I clinical trial.
AB  - Perform a phase I study to evaluate the safety, and tolerability of vorinostat,
      an HDAC inhibitor, when combined with whole brain radiation treatment (WBRT) in
      patients with brain metastasis. A multi-institutional phase I clinical trial
      enrolled patients with a histological diagnosis of malignancy and radiographic
      evidence of brain metastasis. WBRT was 37.5 Gy in 2.5 Gy fractions delivered over
      3 weeks. Vorinostat was administrated by mouth, once daily, Monday through
      Friday, concurrently with radiation treatment. The vorinostat dose was escalated
      from 200 to 400 mg daily using a 3+3 trial design. Seventeen patients were
      enrolled, 4 patients were excluded from the analysis due to either incorrect
      radiation dose (n = 1), or early treatment termination due to disease progression
      (n = 3). There were no treatment related grade 3 or higher toxicities in the 200
      and 300 mg dose levels. In the 400 mg cohort there was a grade 3 pulmonary
      embolus and one death within 30 days of treatment. Both events were most likely
      related to disease progression rather than treatment; nonetheless, we
      conservatively classified the death as a dose limiting toxicity. We found
      Vorinostat administered with concurrent WBRT to be well tolerated to a dose of
      300 mg once daily. This is the recommended dose for phase II study.

PMID- 24728832
TI  - Natural variation underlies alterations in Nramp aluminum transporter (NRAT1)
      expression and function that play a key role in rice aluminum tolerance.
AB  - Aluminum (Al) toxicity is a major constraint for crop production on acid soils
      which compose ~ 40% of arable land in the tropics and subtropics. Rice is the
      most Al-tolerant cereal crop and offers a good model for identifying Al tolerance
      genes and mechanisms. Here we investigated natural variation in the rice Nramp
      aluminum transporter (NRAT1) gene encoding a root plasma membrane Al uptake
      transporter previously hypothesized to underlie a unique Al tolerance mechanism.
      DNA sequence variation in the NRAT1 coding and regulatory regions was associated
      with changes in NRAT1 expression and NRAT1 Al transport properties. These
      sequence changes resulted in significant differences in Al tolerance that were
      found to be associated with changes in the Al content of root cell wall and cell
      sap in 24 representative rice lines from a rice association panel. Expression of
      the tolerant OsNRAT1 allele in yeast resulted in higher Al uptake than did the
      sensitive allele and conferred greater Al tolerance when expressed in transgenic
      Arabidopsis. These findings indicate that NRAT1 plays an important role in rice
      Al tolerance by reducing the level of toxic Al in the root cell wall and
      transporting Al into the root cell, where it is ultimately sequestered in the
      vacuole. Given its ability to enhance Al tolerance in rice and Arabidopsis, this
      work suggests that the NRAT1 gene or its orthologs may be useful tools for
      enhancing Al tolerance in a wide range of plant species.

PMID- 24728833
TI  - Diverse mutational pathways converge on saturable chloroquine transport via the
      malaria parasite's chloroquine resistance transporter.
AB  - Mutations in the chloroquine resistance transporter (PfCRT) are the primary
      determinant of chloroquine (CQ) resistance in the malaria parasite Plasmodium
      falciparum. A number of distinct PfCRT haplotypes, containing between 4 and 10
      mutations, have given rise to CQ resistance in different parts of the world. Here
      we present a detailed molecular analysis of the number of mutations (and the
      order of addition) required to confer CQ transport activity upon the PfCRT as
      well as a kinetic characterization of diverse forms of PfCRT. We measured the
      ability of more than 100 variants of PfCRT to transport CQ when expressed at the
      surface of Xenopus laevis oocytes. Multiple mutational pathways led to saturable
      CQ transport via PfCRT, but these could be separated into two main lineages.
      Moreover, the attainment of full activity followed a rigid process in which
      mutations had to be added in a specific order to avoid reductions in CQ transport
      activity. A minimum of two mutations sufficed for (low) CQ transport activity,
      and as few as four conferred full activity. The finding that diverse PfCRT
      variants are all limited in their capacity to transport CQ suggests that
      resistance could be overcome by reoptimizing the CQ dosage. 

PMID- 24728834
TI  - A thermo-halo-tolerant and proteinase-resistant endoxylanase from Bacillus sp.
      HJ14.
AB  - A glycosyl hydrolase family 10 endoxylanase from Bacillus sp. HJ14 was grouped in
      a separated cluster with another six Bacillus endoxylanases which have not been
      characterized. These Bacillus endoxylanases showed less than 52% amino acid
      sequence identity with other endoxylanases and far distance with endoxylanases
      from most microorganisms. Signal peptide was not detected in the endoxylanase.
      The endoxylanase was expressed in Escherichia coli BL21 (DE3), and the purified
      recombinant enzyme (rXynAHJ14) was characterized. rXynAHJ14 was apparent optimal
      at 62.5  degrees C and pH 6.5 and retained more than 55% of the maximum activity
      when assayed at 40-75  degrees C, 23% at 20  degrees C, 16% at 85  degrees C, and
      even 8% at 0  degrees C. Half-lives of the enzyme were more than 60 min,
      approximately 25 and 4 min at 70, 75, and 80  degrees C, respectively. The enzyme
      exhibited more than 62% xylanase activity and stability at the concentration of 3
      30% (w/v) NaCl. No xylanase activity was lost after incubation of the purified
      rXynAHJ14 with trypsin and proteinase K at 37  degrees C for 60 min. Different
      components of oligosaccharides were detected in the time-course hydrolysis of
      beechwood xylan by the enzyme. During the simulated intestinal digestion phase in
      vitro, 11.5-19.0, 15.3-19.0, 21.9-27.7, and 28.2-31.2 MUmol/mL reducing sugar
      were released by the purified rXynAHJ14 from soybean meal, wheat bran, beechwood
      xylan, and rapeseed meal, respectively. The endoxylanase might be an alternative
      for potential applications in the processing of sea food and saline food and in
      aquaculture as agastric fish feed additive.

PMID- 24728835
TI  - The effects of Losartan on abdominal wall fascial healing.
AB  - PURPOSE: Losartan, a commonly used angiotensin II receptor blocker (ARB) for
      blood pressure control, also impairs cutaneous wound healing. Our current study
      will analyze how Losartan affects wound healing in the muscle and fascia from
      both biomechanical and histological aspects. METHODS: A total of 26 Sprague
      Dawley rats were separated into one control group (NS, N = 13) and one
      experimental group (LG, N = 13) to receive normal saline and 40 mg/kg of Losartan
      by way of gastric lavage, respectively. 7 days later, all animals were subjected
      to a 5 cm midline laparotomy. The fascia and skin were then closed with 4-0
      prolene and 5-0 vicryl. 15 days postoperatively, the animals were sacrificed and
      the abdominal wall harvested for wound tensiometric test and histological
      analysis. RESULTS: All 26 rats survived to the time of necropsy. Tensiometry
      detected significantly higher wound tensile strength in the NS group (1.6 +/-
      0.31 N/mm) than in the LG (1.3 +/- 0.28 N/mm) group (p = 0.016). Transection
      histology with trichrome staining demonstrated higher degree of immature
      fibroplasia inside the wound in the LG group than in the NS group (p = <0.0001).
      The LG group also had larger incisional gaps than the NG group. CONCLUSION: The
      antihypertensive drug, Losartan, retards wound healing in the abdominal fascia
      and reduces wound tensile strength in our rat model. Attention should be paid to
      the potential effects of various medications on fascial wound healing to
      guarantee optimal surgical outcomes.

PMID- 24728836
TI  - Abdominal muscle function and incisional hernia: a systematic review.
AB  - PURPOSE: Although ventral incisional hernia (VIH) repair in patients is often
      evaluated in terms of hernia recurrence rate and health-related quality of life,
      there is no clear consensus regarding optimal operative treatment based on these
      parameters. It was proposed that health-related quality of life depends largely
      on abdominal muscle function (AMF), and the present review thus evaluates to what
      extent AMF is influenced by VIH and surgical repair. METHODS: The PubMed and
      EMBASE databases were searched for articles following a systematic strategy for
      inclusion. RESULTS: A total of seven studies described AMF in relation to VIH.
      Five studies examined AMF using objective isokinetic dynamometers to determine
      muscle strength, and two studies examined AMF by clinical examination-based
      muscle tests. CONCLUSION: Both equipment-related and functional muscle tests
      exist for use in patients with VIH, but very few studies have evaluated AMF in
      VIH. There are no randomized controlled studies to describe the impact of VIH
      repair on AMF, and no optimal surgical treatment in relation to AMF after VIH
      repair can be advocated for at this time.

PMID- 24728837
TI  - Diabetes mellitus among outpatients with COPD attending a university hospital.
AB  - Type 2 diabetes mellitus is a common comorbidity of COPD, but there are still
      many doubts about the relation among diabetes and COPD. We retrospectively
      collected data from patients afferent to our Respiratory Diseases outpatient
      clinic at the Tor Vergata University Hospital between 2010 and 2012. The study
      population was analyzed by clusters of age, gender, body mass index (BMI),
      smoking status, lung function, concomitant pharmacologic therapies and
      comorbidities. The values of the association between variables were expressed as
      odds ratio. Data were adjusted for gender, age and possible confounding variables
      by Mantel-Haenszel method. We identified 493 patients with COPD. Ninety-two (18.7
      %) patients were affected by type 2 diabetes mellitus, with no significant gender
      differences. The prevalence distribution was similar among the different age
      clusters, but the association was stronger in patients younger than 65 years. The
      association was present only in obese subjects in whom it was significant only in
      patients with moderate-to-severe COPD, but not mild COPD. The presence of
      cardiovascular diseases was significantly associated with diabetes mellitus in
      patients with COPD. There was a slight association of inhaled corticosteroid
      (ICS) use with the presence of diabetes mellitus in COPD, but the combination of
      an ICS with a beta2-agonist apparently reduced this association. The association
      with type 2 diabetes mellitus was greater in patients with COPD respect to
      general population, and correlated with the increase in BMI and the presence of
      other comorbidities, suggesting that both diseases may be targets of systemic
      inflammation. 

PMID- 24728838
TI  - The reorganization of motor network in hemidystonia from the perspective of deep
      brain stimulation.
AB  - Hemidystonia is usually 'secondary' to structural lesions within the cortico
      striato-pallido-thalamic or the cerebello-thalamo-cortical loops. Globus pallidus
      internus Deep Brain Stimulation (GPi DBS) is a validated technique in the
      treatment of primary dystonia and still under assessment for secondary dystonia.
      Results of DBS in hemidystonia are limited and heterogeneous. Further knowledge
      concerning motor network organization after focal brain lesions might contribute
      to the understanding of this mitigated response to DBS and to the refinement of
      DBS indications and techniques in secondary dystonia. This study aimed to
      identify movement-related functional magnetic resonance imaging (fMRI) activation
      patterns in a group of hemidystonic patients in comparison to healthy controls
      (HC). Further analysis assessed recruitment pattern in different patient
      subgroups defined according to clinical and radiological criteria relevant to GPi
      DBS eligibility (hyperkinetic/hypokinetic and prepallidal/postpallidal). Eleven
      patients and nine HC underwent fMRI with a block-design alternating active and
      rest conditions. The motor paradigm consisted of self-paced elbow flexion
      extension movements. The main results were as follows: single-subject studies
      revealed several activation patterns involving motor-related network regions;
      both ipsilesional and contralesional hemispheres showed abnormal patterns of
      activity; compared with HC, hemidystonic patients showed decreased brain activity
      in ipsilesional thalamus, pallidal and temporal areas during affected arm task
      execution; 'hypokinetic' subgroup was commonly related to widespread bilateral
      overactivity. This study provides additional arguments for case-by-case
      assessment of DBS surgery indication and target selection in hemidystonia. Single
      lead approach might be unable to modulate a highly disorganized network activity
      in certain patients with this clinical syndrome. 

PMID- 24728839
TI  - Verum and sham acupuncture exert distinct cerebral activation in pain processing
      areas: a crossover fMRI investigation in healthy volunteers.
AB  - Although acupuncture is effective for treating pain, its site-specificity is
      questioned. The aim was to compare the cerebral responses of needling applied to
      an acupuncture point to the needling of a sham point, using functional magnetic
      resonance imaging (fMRI). Twenty-one healthy male volunteers were enrolled.
      Manual stimulation of the acupuncture (ST44) and sham points on the dorsum of the
      left foot was applied during fMRI in a crossover manner. fMRI data analysis was
      performed contrasting the ST44 and the sham conditions. Stimulation intensity,
      subjective discrimination of the needling site and the incidence of "Qi"
      sensation were additionally recorded. Stimulation of ST44 acupoint, in comparison
      to the sham procedure, was associated with an increased fMRI-activation in the
      primary somatosensory, the inferior parietal and the prefrontal cortex and the
      posterior insula. Sham needling was associated with increased activation in the
      anterior cingulate cortex and the anterior insula. Verum acupuncture increased
      the activity of discriminative somatosensory and cognitive pain processing areas
      of the brain, whereas sham needling activated the areas responsible for affective
      processing of pain. This may explain favorable effects of verum acupuncture in
      clinical studies about treatment of chronic pain patients. 

PMID- 24728842
TI  - MMN: from immunological cross-talk to conduction block.
AB  - Multifocal motor neuropathy (MMN) is a rare inflammatory neuropathy characterized
      by progressive, asymmetric distal limb weakness and conduction block (CB).
      Clinically MMN is a pure motor neuropathy, which as such can mimic motor neuron
      disease. GM1-specific IgM antibodies are present in the serum of approximately
      half of all MMN patients, and are thought to play a key role in the immune
      pathophysiology. Intravenous immunoglobulin (IVIg) treatment has been shown to be
      effective in MMN in five randomized placebo-controlled trials. Despite long-term
      treatment with intravenous immunoglobulin (IVIg), which is efficient in the
      majority of patients, slowly progressive axonal degeneration and subsequent
      muscle weakness cannot be fully prevented. In this review, we will discuss the
      current understanding of the immune pathogenesis underlying MMN and how this may
      cause CB, available treatment strategies and future therapeutic targets. 

PMID- 24728843
TI  - Role of FcgammaRIIIA (CD16) in IVIg-mediated anti-inflammatory function.
AB  - The mechanism for anti-inflammatory action of intravenous immunoglobulin (IVIg)
      in the treatment of autoimmune and inflammatory diseases involves IgG Fc
      receptors (FcgammaR). Although the inhibitory FcgammaRIIB plays an important role
      in IVIg action, FcgammaRIIIA has recently been identified as another major anti
      inflammatory actor. Interaction of FcgammaRIIIA with uncomplexed IgG1 or IVIg, or
      with bivalent anti-FcgammaRIII F(ab')2 dampened calcium responses, ROS
      production, endocytosis and phagocytosis, induced by heterologous activating
      receptors. This inhibitory action required the inhibitory configuration of the
      ITAM motif (ITAMi) present within the FcgammaRIII-associated FcRgamma subunit.
      This allowed SHP-1 recruitment and formation of intracellular inhibisome clusters
      containing FcgammaRIII and the targeted activating receptor. Therefore, IVIg
      functionally interact with FcgammaRIIIA inducing ITAMi signaling which can
      prevent development of autoimmune and inflammatory disorders independently of
      FcgammaRIIB. This new mechanism of action for IVIg reveals a therapeutic
      potential for FcgammaRIIIA targeting in inflammatory diseases. 

PMID- 24728844
TI  - CHD7, the gene mutated in CHARGE syndrome, regulates genes involved in neural
      crest cell guidance.
AB  - Heterozygous loss of function mutations in CHD7 (chromodomain helicase DNA
      binding protein 7) lead to CHARGE syndrome, a complex developmental disorder
      affecting craniofacial structures, cranial nerves and several organ systems.
      Recently, it was demonstrated that CHD7 is essential for the formation of
      multipotent migratory neural crest cells, which migrate from the neural tube to
      many regions of the embryo, where they differentiate into various tissues
      including craniofacial and heart structures. So far, only few CHD7 target genes
      involved in neural crest cell development have been identified and the role of
      CHD7 in neural crest cell guidance and the regulation of mesenchymal-epithelial
      transition are unknown. Therefore, we undertook a genome-wide microarray
      expression analysis on wild-type and CHD7 deficient (Chd7 (Whi/+) and Chd7
      (Whi/Whi)) mouse embryos at day 9.5, a time point of neural crest cell migration.
      We identified 98 differentially expressed genes between wild-type and Chd7
      (Whi/Whi) embryos. Interestingly, many misregulated genes are involved in neural
      crest cell and axon guidance such as semaphorins and ephrin receptors. By
      performing knockdown experiments for Chd7 in Xenopus laevis embryos, we found
      abnormalities in the expression pattern of Sema3a, a protein involved in the
      pathogenesis of Kallmann syndrome, in vivo. In addition, we detected non
      synonymous SEMA3A variations in 3 out of 45 CHD7-negative CHARGE patients. In
      summary, we discovered for the first time that Chd7 regulates genes involved in
      neural crest cell guidance, demonstrating a new aspect in the pathogenesis of
      CHARGE syndrome. Furthermore, we showed for Sema3a a conserved regulatory
      mechanism across different species, highlighting its significance during
      development. Although we postulated that the non-synonymous SEMA3A variants which
      we found in CHD7-negative CHARGE patients alone are not sufficient to produce the
      phenotype, we suggest an important modifier role for SEMA3A in the pathogenesis
      of this multiple malformation syndrome.

PMID- 24728846
TI  - Extracorporeal shock wave therapy for non-calcific supraspinatus tendinitis - 10
      year follow-up of a randomized placebo-controlled trial.
AB  - Evidence for the efficacy of extracorporeal shock wave therapy (ESWT) in
      supraspinatus tendinopathy without calcification is sparse, and therefore this
      treatment option is often controversial. Patients of a randomized placebo
      controlled study to analyze the effects of ESWT on function and pain were
      revisited 10 years after the initial consultation. The former verum group
      received 6000 impulses (energy flux density, 0.11 mJ/mm2) in three sessions after
      local anesthesia between 1999 and 2000. The placebo group had 6000 impulses of a
      sham ESWT after local anesthesia in the same period. Re-evaluation of the
      patients included a relative Constant score as well as pain measurements (visual
      analogue scale) during activity and at rest. No significant changes (p>0.05) in
      relative Constant scores, pain at rest, or pain during activity could be found
      after a 10-year follow-up between the placebo and verum groups after ESWT. The
      treatment of non-calcific supraspinatus tendinopathy with ESWT does not seem to
      have an effect on function or pain improvement in the long run. The results of
      the present study cannot advise the use of ESWT in cases of non-calcific
      supraspinatus tendinopathy.

PMID- 24728847
TI  - Perinatal outcome of congenital heart disease in a population with high
      consanguinity.
AB  - OBJECTIVE: To report the perinatal pattern and outcome of fetuses with congenital
      heart disease (CHD) in consanguineous marriages. METHODS: Retrospective chart
      review was performed for fetuses undergoing fetal echocardiography (FE) in our
      institution. The primary outcome was survival at 28 days after birth. RESULTS:
      Between 1 January 2005 and 31 December 2010, 1950 pregnant women carrying 2151
      fetuses underwent a total of 2828 FEs. CHD was diagnosed in 152 fetuses (7.1%),
      and perinatal outcome was available in 120, among which 78 (65%) had
      consanguineous parents. Thirteen fetuses died in utero, while 86 (71.7%)
      survived. The most prevalent lesions included left heart obstruction (25.8%),
      conotruncal malformations (21.7%), septal defects (18.3%), and cardiomyopathy
      (15.8%). Correct diagnosis was achieved in 92.2% of the cases. Extracardiac
      malformations occurred in 48.3% of the fetuses and were associated with increased
      mortality regardless of the type of CHD (P<0.001, odds ratio 6.8, 95% confidence
      interval 2.7-17.5). CONCLUSION: Joint FE clinics detect most CHD with high
      accuracy. Consanguinity contributes to a higher prevalence of fetal cardiac and
      non-cardiac malformations. The presence of extracardiac anomalies is associated
      with an increase in perinatal mortality.

PMID- 24728845
TI  - Cannabis use is a better indicator of poor mental health in women than in men: a
      cross-sectional study in young adults from the general population.
AB  - Cannabis use is a known risk factor for a range of mental health problems, but
      less is known on the association with general mental health. We aim to explore
      the relationship between cannabis use and general mental health. We did a cross
      sectional online survey of 1,929 young adults aged 18-30 years. Participants
      reported socio-demographic data, substance use and the Symptom Checklist-90 (SCL
      90). Monthly cannabis use was associated with a higher total score on the SCL-90,
      both in a crude (OR 1.94, 95% CI 1.57-2.38) and fully adjusted model (OR 1.48,
      95% CI 1.07-2.03). The association between cannabis and mental health was
      stronger in women and weekly users, and was independent of age at first use of
      cannabis. We conclude that moderate cannabis use is associated with general
      mental health problems in young adulthood. This relationship is independent of
      age at first use and of other risk factors, and is strongest in women.

PMID- 24728848
TI  - Adverse perinatal outcomes related to the delivery mode in women with
      monochorionic diamniotic twin pregnancies.
AB  - AIMS: The association between the planned delivery mode and adverse perinatal
      outcomes of monochorionic diamniotic (MCDA) twin pregnancies at >=36 weeks'
      gestation was evaluated. METHODS: This retrospective cohort study included
      uncomplicated MCDA twin pregnancies delivered after 36 weeks' gestation during a
      10-year period. Cases were classified into the trial of labor (TOL) or cesarean
      section (CS) group according to the planned delivery mode. The primary outcome
      was a composite of adverse outcomes for at least one twin, including intrauterine
      fetal death (IUFD) after 36 weeks, neonatal death, umbilical artery pH<7.1, 5-min
      Apgar scores<7, hypoxic ischemic encephalopathy (HIE), meconium aspiration
      syndrome (MAS), respiratory distress syndrome (RDS), or acute feto-fetal
      hemorrhage (AFFH). The relationship between outcomes and the planned delivery
      mode was evaluated using a multiple logistic regression analysis. RESULTS: We
      included the 310 pregnancies delivered after 36 weeks' gestation. After excluding
      15 patients, the final analysis included 295 MCDA pregnancies: 63% had delivered
      through TOL and 37% through CS. The incidences of composite adverse outcomes in
      the TOL and CS groups were 4.3% and 1.9%, respectively. No IUFD, neonatal death,
      MAS, RDS, or AFFH was observed; two infants in each group developed HIE. Adverse
      outcomes were not significantly associated with any risk factor, including
      delivery through TOL. CONCLUSION: TOL may not influence the perinatal outcomes of
      MCDA twin pregnancies delivered at >=36 weeks' gestation.

PMID- 24728849
TI  - The factors associated with the failure of transcatheter pelvic arterial
      embolization for intractable postpartum hemorrhage.

PMID- 24728850
TI  - FlashFISHTM: a novel technique for rapid diagnosis of aneuploidies in dysmorphic
      neonates.

PMID- 24728851
TI  - Severe left ventricular systolic dysfunction is independently associated with
      high on-clopidogrel platelet reactivity.
AB  - OBJECTIVE: The purpose of the present study was to investigate the association
      between left ventricular systolic function and the response to clopidogrel.
      METHODS: The efficacy of clopidogrel was measured by the vasodilator-stimulated
      phosphoprotein phosphorylation 20 +/- 4 h after 600 mg of clopidogrel. High on
      clopidogrel platelet reactivity (HCPR) was defined as a platelet reactivity index
      (PRI) >=50%. The 30-day combined incidence of death, non-fatal acute coronary
      syndrome, re-percutaneous coronary intervention (PCI), stent thrombosis, and
      stroke was also investigated. RESULTS: The study group consisted of 519 patients
      undergoing PCI. The values (mean and 95% confidence interval) of the PRI were as
      follows: 40.4% (37.8-43.0) in patients with left ventricular ejection fraction
      (LVEF) >50%, 42.4% (39.3-45.6) in patients with LVEF 35-50%, and 46.7% (40.6
      52.9) in patients with LVEF <35% (p = 0.013). The proportions of patients with
      HCPR were 35.9% in patients with LVEF >=35 and 51.9% in patients with LVEF <35%
      (p = 0.022). After adjustment for variables that significantly influenced
      clopidogrel efficacy, LVEF <35% was found to be independently associated with
      HCPR (p = 0.039). The 30-day combined clinical endpoint occurred in 18% of
      patients with LVEF <35% and in 7.3% of patients with LVEF >=35% (p = 0.026). The
      30-day incidence of all-cause mortality was 14% in patients with LVEF <35 and
      1.0% in patients with LVEF >=35% (p < 0.001). CONCLUSION: An LVEF <35% was found
      to be independently associated with HCPR.

PMID- 24728852
TI  - Direct calculation of elementary flux modes satisfying several biological
      constraints in genome-scale metabolic networks.
AB  - MOTIVATION: The concept of Elementary Flux Mode (EFM) has been widely used for
      the past 20 years. However, its application to genome-scale metabolic networks
      (GSMNs) is still under development because of methodological limitations.
      Therefore, novel approaches are demanded to extend the application of EFMs. A
      novel family of methods based on optimization is emerging that provides us with a
      subset of EFMs. Because the calculation of the whole set of EFMs goes beyond our
      capacity, performing a selective search is a proper strategy. RESULTS: Here, we
      present a novel mathematical approach calculating EFMs fulfilling additional
      linear constraints. We validated our approach based on two metabolic networks in
      which all the EFMs can be obtained. Finally, we analyzed the performance of our
      methodology in the GSMN of the yeast Saccharomyces cerevisiae by calculating EFMs
      producing ethanol with a given minimum carbon yield. Overall, this new approach
      opens new avenues for the calculation of EFMs in GSMNs. AVAILABILITY AND
      IMPLEMENTATION: Matlab code is provided in the supplementary online materials
      CONTACT: fplanes@ceit.es. SUPPLEMENTARY INFORMATION: Supplementary data are
      available at Bioinformatics online.

PMID- 24728853
TI  - Codon Optimization OnLine (COOL): a web-based multi-objective optimization
      platform for synthetic gene design.
AB  - SUMMARY: Codon optimization has been widely used for designing synthetic genes to
      improve their expression in heterologous host organisms. However, most of the
      existing codon optimization tools consider a single design criterion and/or
      implement a rather rigid user interface to yield only one optimal sequence, which
      may not be the best solution. Hence, we have developed Codon Optimization OnLine
      (COOL), which is the first web tool that provides the multi-objective codon
      optimization functionality to aid systematic synthetic gene design. COOL supports
      a simple and flexible interface for customizing various codon optimization
      parameters such as codon adaptation index, individual codon usage and codon
      pairing. In addition, users can visualize and compare the optimal synthetic
      sequences with respect to various fitness measures. User-defined DNA sequences
      can also be compared against the COOL optimized sequences to show the extent by
      which the user's sequences can be further improved. AVAILABILITY AND
      IMPLEMENTATION: COOL is free to academic and non-commercial users and licensed to
      others for a fee by the National University of Singapore. Accessible at
      http://bioinfo.bti.a-star.edu.sg/COOL/ CONTACT: cheld@nus.edu.sg SUPPLEMENTARY
      INFORMATION: Supplementary data are available at Bioinformatics online.

PMID- 24728854
TI  - methylC Track: visual integration of single-base resolution DNA methylation data
      on the WashU EpiGenome Browser.
AB  - SUMMARY: We present methylC track, an efficient mechanism for visualizing single
      base resolution DNA methylation data on a genome browser. The methylC track
      dynamically integrates the level of methylation, the position and context of the
      methylated cytosine (i.e. CG, CHG and CHH), strand and confidence level (e.g.
      read coverage depth in the case of whole-genome bisulfite sequencing data).
      Investigators can access and integrate these information visually at specific
      locus or at the genome-wide level on the WashU EpiGenome Browser in the context
      of other rich epigenomic datasets. AVAILABILITY AND IMPLEMENTATION: The methylC
      track is part of the WashU EpiGenome Browser, which is open source and freely
      available at http://epigenomegateway.wustl.edu/browser/. The most up-to-date
      instructions and tools for preparing methylC track are available at
      http://epigenomegateway.wustl.edu/+/cmtk. CONTACT: twang@genetics.wustl.edu
      SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics
      online.

PMID- 24728855
TI  - geiger v2.0: an expanded suite of methods for fitting macroevolutionary models to
      phylogenetic trees.
AB  - SUMMARY: Phylogenetic comparative methods are essential for addressing
      evolutionary hypotheses with interspecific data. The scale and scope of such data
      have increased dramatically in the past few years. Many existing approaches are
      either computationally infeasible or inappropriate for data of this size. To
      address both of these problems, we present geiger v2.0, a complete overhaul of
      the popular R package geiger. We have reimplemented existing methods with more
      efficient algorithms and have developed several new approaches for accomodating
      heterogeneous models and data types. AVAILABILITY AND IMPLEMENTATION:  This R
      package is available on the CRAN repository http://cran.r
      project.org/web/packages/geiger/. All source code is also available on github
      http://github.com/mwpennell/geiger-v2. geiger v2.0 depends on the ape package.
      CONTACT: mwpennell@gmail.com SUPPLEMENTARY INFORMATION:  Supplementary data are
      available at Bioinformatics online.

PMID- 24728856
TI  - Lossy compression of quality scores in genomic data.
AB  - MOTIVATION: Next-generation sequencing technologies are revolutionizing medicine.
      Data from sequencing technologies are typically represented as a string of bases,
      an associated sequence of per-base quality scores and other metadata, and in
      aggregate can require a large amount of space. The quality scores show how
      accurate the bases are with respect to the sequencing process, that is, how
      confident the sequencer is of having called them correctly, and are the largest
      component in datasets in which they are retained. Previous research has examined
      how to store sequences of bases effectively; here we add to that knowledge by
      examining methods for compressing quality scores. The quality values originate in
      a continuous domain, and so if a fidelity criterion is introduced, it is possible
      to introduce flexibility in the way these values are represented, allowing lossy
      compression over the quality score data. RESULTS: We present existing compression
      options for quality score data, and then introduce two new lossy techniques.
      Experiments measuring the trade-off between compression ratio and information
      loss are reported, including quantifying the effect of lossy representations on a
      downstream application that carries out single nucleotide polymorphism and
      insert/deletion detection. The new methods are demonstrably superior to other
      techniques when assessed against the spectrum of possible trade-offs between
      storage required and fidelity of representation. AVAILABILITY AND IMPLEMENTATION:
      An implementation of the methods described here is available at
      https://github.com/rcanovas/libCSAM. CONTACT: rcanovas@student.unimelb.edu.au
      SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics
      online.

PMID- 24728857
TI  - Computational identification of natural peptides based on analysis of molecular
      evolution.
AB  - MOTIVATION: Many secretory peptides are synthesized as inactive precursors that
      must undergo post-translational processing to become biologically active
      peptides. Attempts to predict natural peptides are limited by the low performance
      of proteolytic site predictors and by the high combinatorial complexity of
      pairing such sites. To overcome these limitations, we analyzed the site-wise
      evolutionary mutation rates of peptide hormone precursors, calculated using the
      Rate4Site algorithm. RESULTS: Our analysis revealed that within their precursors,
      peptide residues are significantly more conserved than the pro-peptide residues.
      This disparity enables the prediction of peptides with a precision of ~60% at a
      recall of 40% [receiver-operating characteristic curve (ROC) AUC 0.79].
      Subsequently, combining the Rate4Site score with additional features and training
      a Random Forest classifier enable the prediction of natural peptides hidden
      within secreted human proteins at a precision of ~90% at a recall of 50% (ROC AUC
      0.96). The high performance of our method allows it to be applied to full
      secretomes and to predict naturally occurring active peptides. Our prediction on
      Homo sapiens revealed several putative peptides in the human secretome that are
      currently unannotated. Furthermore, the unique expression of some of these
      peptides implies a potential hormone function, including peptides that are highly
      expressed in endocrine glands. AVAILABILITY AND IMPLEMENTATION: A pseudocode is
      available in the SUPPLEMENTARY INFORMATION. CONTACT: doron.gerber@biu.ac.il or
      kliger@cgen.com SUPPLEMENTARY INFORMATION: Supplementary data are available at
      Bioinformatics online.

PMID- 24728859
TI  - A comprehensive comparison of association estimators for gene network inference
      algorithms.
AB  - MOTIVATION: Gene network inference (GNI) algorithms enable the researchers to
      explore the interactions among the genes and gene products by revealing these
      interactions. The principal process of the GNI algorithms is to obtain the
      association scores among genes. Although there are several association estimators
      used in different applications, there is no commonly accepted estimator as the
      best one for the GNI applications. In this study, 27 different interaction
      estimators were reviewed and 14 most promising ones among them were evaluated by
      using three popular GNI algorithms with two synthetic and two real biological
      datasets belonging to Escherichia coli bacteria and Saccharomyces cerevisiae
      yeast. Influences of the Copula Transform (CT) pre-processing operation on the
      performance of the interaction estimators are also observed. This study is
      expected to assist many researchers while studying with GNI applications.
      RESULTS: B-spline, Pearson-based Gaussian and Spearman-based Gaussian association
      score estimators outperform the others for all datasets in terms of the
      performance and runtime. In addition to this, it is observed that, when the CT
      operation is used, inference performances of the estimators mostly increase,
      especially for two synthetic datasets. Detailed evaluations and discussions are
      given in the experimental results. CONTACT: gokmen.altay@bahcesehir.edu.tr
      SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics
      online.

PMID- 24728858
TI  - A change-point model for identifying 3'UTR switching by next-generation RNA
      sequencing.
AB  - MOTIVATION: Next-generation RNA sequencing offers an opportunity to investigate
      transcriptome in an unprecedented scale. Recent studies have revealed widespread
      alternative polyadenylation (polyA) in eukaryotes, leading to various mRNA
      isoforms differing in their 3' untranslated regions (3'UTR), through which, the
      stability, localization and translation of mRNA can be regulated. However, very
      few, if any, methods and tools are available for directly analyzing this special
      alternative RNA processing event. Conventional methods rely on annotation of
      polyA sites; yet, such knowledge remains incomplete, and identification of polyA
      sites is still challenging. The goal of this article is to develop methods for
      detecting 3'UTR switching without any prior knowledge of polyA annotations.
      RESULTS: We propose a change-point model based on a likelihood ratio test for
      detecting 3'UTR switching. We develop a directional testing procedure for
      identifying dramatic shortening or lengthening events in 3'UTR, while controlling
      mixed directional false discovery rate at a nominal level. To our knowledge, this
      is the first approach to analyze 3'UTR switching directly without relying on any
      polyA annotations. Simulation studies and applications to two real datasets
      reveal that our proposed method is powerful, accurate and feasible for the
      analysis of next-generation RNA sequencing data. CONCLUSIONS: The proposed method
      will fill a void among alternative RNA processing analysis tools for
      transcriptome studies. It can help to obtain additional insights from RNA
      sequencing data by understanding gene regulation mechanisms through the analysis
      of 3'UTR switching. AVAILABILITY AND IMPLEMENTATION: The software is implemented
      in Java and can be freely downloaded from http://utr.sourceforge.net/. CONTACT:
      zhiwei@njit.edu or hongzhe@mail.med.upenn.edu SUPPLEMENTARY INFORMATION:
      Supplementary data are available at Bioinformatics online.

PMID- 24728860
TI  - Stability and degradation patterns of chemically modified analogs of apelin-13 in
      plasma and cerebrospinal fluid.
AB  - Apelin is the endogenous ligand of APJ, which belongs to the superfamily of G
      protein-coupled receptors. In recent years, the apelin/APJ system has been
      detected in many tissues and emerges as a promising target for the treatment of
      various pathophysiological conditions. Pyr1-apelin-13 is the major isoform of
      apelin in human plasma; however its stability and proteolytic degradation pattern
      remain poorly understood. The aim of the present study was first to identify the
      cleavage sites of Pyr1-apelin-13 in mouse, rat and human plasma and rat
      cerebrospinal fluid, then to determine its stability to proteolytic degradation
      following intravenous administration in rats. Secondly, key residues were
      substituted by natural and unnatural amino acids in order to examine the impact
      on in vitro stability and degradation pattern. The kinetics of degradation
      revealed that the Leu5-Ser6 peptide bond of Pyr1-apelin-13 is the first cleavage
      observed in plasma, independently of the species. Replacement of Phe13 by
      unnatural amino acids showed a 10-fold increase in plasma stability although the
      hydrolysis of Pro12-Phe13 bond, previously described as a site of cleavage by ACE
      2, was not observed. In vivo, this Pro12-Phe13 bond was cleaved yet appears as a
      minor product compared to hydrolysis of the Pro10-Met11 bond. This study
      pinpoints the most critical amino acids targeted by proteases and will be
      instrumental for the design of Pyr1-apelin-13 analogs possessing increased
      stability.

PMID- 24728861
TI  - Aflatoxin B1-Induced Reproductive Toxicity in Male Rats: Possible Mechanism of
      Action.
AB  - Aflatoxin B1 (AFB1), one of the most common mycotoxins found in human foods, is
      principally hepatotoxic; however, it also affects reproduction. The aim of the
      present study was to elucidate the reproductive toxic effects and possible
      mechanism of action of AFB1 in rats. Male Wistar rats were injected
      intramuscularly with doses of 10, 20, or 50 ug AFB1/kg body weight on alternate
      days from 45 to 100 days of age. Significant reductions in body weights, relative
      weights of reproductive organs, daily sperm production, epididymal sperm count,
      viable sperm, motile sperm, and hypoosmotic swelling-tail coiled sperm were
      observed. Significant decreases in testicular steroidogenic enzymes and serum
      testosterone levels were also observed indicating decreased steroidogenesis. In
      silico docking studies illustrated AFB1 binds with steroidogenic acute regulatory
      (StAR) protein thereby affecting the transport of cholesterol into mitochondria
      resulting in decreased steroidogenesis.

PMID- 24728863
TI  - An optimized transformation protocol for Lipomyces starkeyi.
AB  - We report the development of an efficient genetic transformation system for
      Lipomyces starkeyi based on a modified lithium acetate transformation protocol.
      L. starkeyi is a highly lipogenic yeast that grows on a wide range of substrates.
      The initial transformation rate for this species was extremely low, and required
      very high concentrations of DNA. A systematic approach for optimizing the
      protocol resulted in an increase in the transformation efficiency by four orders
      of magnitude. Important parameters included cell density, the duration of
      incubation and recovery periods, the heat shock temperature, and the
      concentration of lithium acetate and carrier DNA within the transformation
      mixture. We have achieved efficiencies in excess of 8,000 transformants/ug DNA,
      which now make it possible to screen libraries in the metabolic engineering of
      this yeast. Metabolic engineering based on this transformation system could
      improve lipogenesis and enable formation of higher value products. 

PMID- 24728862
TI  - Tissue-Specific Induction of Mouse ZIP8 and ZIP14 Divalent Cation/Bicarbonate
      Symporters by, and Cytokine Response to, Inflammatory Signals.
AB  - Mouse Slc39a8 and Slc39a14 genes encode ZIP8 and ZIP14, respectively, which are
      ubiquitous divalent cation/(HCO3-)2 symporters responsible for uptake of Zn2+,
      Fe2+, and Mn2+ into cells. Cd2+ and other toxic nonessential metals can displace
      essential cations, thereby entering vertebrate cells. Whereas Slc39a8 encodes a
      single protein, Slc39a14 has 2 exons 4 which, via alternative splicing, give rise
      to ZIP14A and ZIP14B; why differences exist in cell type-specific expression of
      ZIP14A and ZIP14B remains unknown. Inflammatory stimuli have been associated with
      upregulation of ZIP8 and ZIP14, but a systematic study of many tissues
      simultaneously in a laboratory animal following inflammatory cytokine exposure
      has not yet been reported. Herein, we show that C57BL/6J male mice--treated
      intraperitoneally with lipopolysaccharide or the proinflammatory cytokines tumor
      necrosis factor (TNF) or interleukin-6 (IL6)--exhibited quantatively very
      different, highly tissue-specific, and markedly time-dependent up- and
      downregulation of ZIP8, ZIP14A, and ZIP14B messenger RNA (mRNA) levels in 12
      tissues. The magnitude of inflammatory response was confirmed by measuring the
      proinflammatory cytokine TNF, IL6, and interleukin-1beta mRNA levels in the same
      tissues of these animals. Our data suggest that most if not all tissues use ZIP8,
      ZIP14A, and/or ZIP14B for Zn2+ uptake, some tissues under basal conditions and
      others moreso when inflammatory stressors are present; collectively, this might
      lead to substantial alterations in plasma Zn2+ levels due to Zn2+ redistribution
      not just in liver but across many vital organs. In the context of cadmium
      mediated toxicity, our data suggest that tissues other than liver, kidney, and
      lung should also be considered.

PMID- 24728864
TI  - Measuring subject specific muscle model parameters of the first dorsal
      interosseous in vivo.
AB  - Subject specific musculoskeletal models typically base some or all of their
      parameters on a source other than the subject being modeled. Evidence
      demonstrates that cadaveric measurements do not always scale appropriately to
      every subject, yet many musculoskeletal models still rely heavily on cadaveric
      based data. This study focused on the First Dorsal interosseous (FDI) given its
      unique function as the sole abductor of the second metacarpophalangeal joint.
      There were two purposes to this study: (1) to describe the procedures that can be
      used in vivo to determine the properties of a model of the FDI. (2). To determine
      the model parameters required to characterize the FDI for a group of four
      subjects. Parameters were determined using ultrasound imaging and a custom-built
      finger dynamometer. Some parameters were measured directly while other parameters
      had to be estimated using a least-squares criterion. For example, the parameters
      for the force-length properties were determined by fitting a model to
      experimentally determined data, with maximum isometric force values ranging from
      86 to 102 N, and optimum lengths from 41 to 53 mm. It was shown that full
      characterization is possible for the FDI with parameters that are physiologically
      reasonable, but which showed variability between subjects. This model and
      approach for parameter identification will allow for more detailed analysis of
      the function of the FDI. 

PMID- 24728865
TI  - Validation of algorithms for the estimation of pulse transit time: where do we
      stand today? Response to commentaries by Papaioannou et al.

PMID- 24728866
TI  - Impact of extent of antral resection on surgical outcomes of sleeve gastrectomy
      for morbid obesity (a prospective randomized study).
AB  - BACKGROUND: Laparoscopic sleeve gastrectomy (LSG) is a surgical technique that
      treats morbid obesity. METHODS: Consecutive patients with morbid obesity treated
      by LSG at our department were evaluated. Patients enrolled in the study were
      randomized into group I (LSG begins the division 2 cm from the pylorus) and group
      II (LSG begins the division 6 cm from the pylorus). The primary outcome measure
      was the percent of excess weight loss (% EWL); secondary outcomes included
      postoperative morbidity and mortality and improvement of comorbidity. RESULTS:
      One hundred five patients (79 (75.2 %) were females) were randomized into two
      groups of (GI) 52 patients and (GII) 53 patients. In group I, the mean % EWL was
      51.8 +/- 13.9, 63.8 +/- 16.1 and 71.8 +/- 12; however, in group II, the mean %
      EWL was 38.3 +/- 10.9, 51.9 +/- 13.6 and 61 +/- 11.1 at 6, 12, and 24 months,
      respectively (P = 0.0001, 0.0001, 0.003). There was weight regain after 2 years
      in five patients in group II and only one patient in group I (P = 0.09). There
      was no significant difference between both group as regards gastric leakage,
      vomiting or GER. There was significant improvement in comorbidity after LSG in
      both groups, but no significant difference between them. Hospital mortality
      occurred in group II in one case as a result of gastric leakage. CONCLUSIONS: LSG
      is a safe and effective procedure with good short-term outcome. Increasing the
      size of the resected antrum is associated with better weight loss without
      increasing the rate of complications significantly.

PMID- 24728867
TI  - Sazetidine-A Activates and Desensitizes Native alpha7 Nicotinic Acetylcholine
      Receptors.
AB  - The aim of this study was to investigate the ability of sazetidine-A, a novel
      partial agonist at alpha4beta2 nicotinic acetylcholine receptors (nAChRs), to
      affect the function of native alpha7 nAChRs in SH-SY5Y cells and primary cortical
      cultures. The alpha7-selective positive allosteric modulator PNU-120596 was used
      to reveal receptor activation, measured as an increase in intracellular calcium
      using fluorescent indicators. In the absence of PNU-120596, sazetidine-A elicited
      mecamylamine-sensitive increases in fluorescence in SH-SY5Y cells (EC50 4.2 uM)
      but no responses from primary cortical neurons. In the presence on PNU-120596, an
      additional response to sazetidine-A was observed in SH-SY5Y cells (EC50 0.4 uM)
      and robust responses were recorded in 14 % of cortical neurons. These PNU-120596
      dependent responses were blocked by methyllycaconitine, consistent with the
      activation of alpha7 nAChRs. Preincubtion with sazetidine-A concentration
      dependently attenuated subsequent responses to the alpha7-selective agonist PNU
      282987 in SH-SY5Y cells (IC50 476 nM) and cortical cultures. These findings
      support the ability of sazetidine-A to interact with alpha7 nAChRs, which may
      contribute to sazetidine-A's actions in complex physiological systems.

PMID- 24728870
TI  - Y-P30 promotes axonal growth by stabilizing growth cones.
AB  - The 30-amino acid peptide Y-P30, generated from the N-terminus of the human
      dermcidin precursor protein, has been found to promote neuronal survival, cell
      migration and neurite outgrowth by enhancing the interaction of pleiotrophin and
      syndecan-3. We now show that Y-P30 activates Src kinase and extracellular signal
      regulated kinase (ERK). Y-P30 promotes axonal growth of mouse embryonic stem cell
      derived neurons, embryonic mouse spinal cord motoneurons, perinatal rat retinal
      neurons, and rat cortical neurons. Y-P30-mediated axon growth was dependent on
      heparan sulfate chains. Y-P30 decreased the proportion of collapsing/degenerating
      growth cones of cortical axons in an Src and ERK-dependent manner. Y-P30
      increased for 90 min in axonal growth cones the level of Tyr418-phosphorylated
      Src kinase and the amount of F-actin, and transiently the level of Tyr
      phosphorylated ERK. Levels of total Src kinase, actin, GAP-43, cortactin and the
      glutamate receptor subunit GluN2B were not altered. When exposed to semaphorin
      3a, Y-P30 protected a significant fraction of growth cones of cortical neurons
      from collapse. These results suggest that Y-P30 promotes axonal growth via Src-
      and ERK-dependent mechanisms which stabilize growth cones and confer resistance
      to collapsing factors.

PMID- 24728871
TI  - Combinatorial analysis of calcium-binding proteins in larval and adult zebrafish
      primary olfactory system identifies differential olfactory bulb glomerular
      projection fields.
AB  - In the zebrafish (Danio rerio) olfactory epithelium, the calcium-binding proteins
      (CBPs) calretinin and S100/S100-like protein are mainly expressed in ciliated or
      crypt olfactory sensory neurons (OSNs), respectively. In contrast parvalbumin and
      calbindin1 have not been investigated. We present a combinatorial
      immunohistological analysis of all four CBPs, including their expression in OSNs
      and their axonal projections to the olfactory bulb in larval and adult zebrafish.
      A major expression of calretinin and S100 in ciliated and crypt cells,
      respectively, with some expression of S100 in microvillous cells is confirmed.
      Parvalbumin and calbindin1 are strongly expressed in ciliated and microvillous
      cells, but not in crypt cells. Moreover, detailed combinatorial double-label
      experiments indicate that there are eight subpopulations of zebrafish OSNs: S100
      positive crypt cells (negative for all other three CBPs), parvalbumin only, S100
      and parvalbumin, parvalbumin and calbindin1, and parvalbumin and calbindin1 and
      calretinin-positive microvillous OSNs, as well as a major parvalbumin and
      calbindin1 and calretinin, and minor parvalbumin and calbindin1 and calretinin
      only-positive ciliated OSN populations. CBP-positive projections to olfactory
      bulb are consistent with previous reports of ciliated OSNs projecting to dorsal
      and ventromedial glomerular fields and microvillous OSNs to ventrolateral
      glomerular fields. We newly describe parvalbumin-positive fibers to the
      mediodorsal field which is calretinin free, with its anterior part showing
      additionally calbindin1-positive fibers, but absence thereof in the posterior
      part, indicating an origin from microvillous OSNs in both parts. One singular
      glomerulus (mdG2) exhibits S100 and parvalbumin-positive fibers, apparently
      originating from all crypt cells plus some microvillous OSNs. Arguments for
      various olfactory labeled lines are discussed. 

PMID- 24728868
TI  - Advances in device and formulation technologies for pulmonary drug delivery.
AB  - Inhaled pharmaceuticals are formulated and delivered differently according to the
      therapeutic indication. However, specific device-formulation coupling is often
      fickle, and new medications or indications also demand new strategies. The
      discontinuation of chlorofluorocarbon propellants has seen replacement of older
      metered dose inhalers with dry powder inhaler formulations. High-dose dry powder
      inhalers are increasingly seen as an alternative dosage form for nebulised
      medications. In other cases, new medications have completely bypassed
      conventional inhalers and been formulated for use with unique inhalers such as
      the Staccato(r) device. Among these different devices, integration of software
      and electronic assistance has become a shared trend. This review covers recent
      device and formulation advances that are forming the current landscape of inhaled
      therapeutics. 

PMID- 24728875
TI  - Risk assessment visualization of rubidium compounds: comparison of renal and
      hepatic toxicities, in vivo.
AB  - Rubidium has been considered to be nontoxic. Its use includes thin film on glass
      deposition and as medical contrast medium. Recent technology innovations also
      involve the use of rubidium, but there is limited information about the
      biological effects of its various compounds. In the present risk assessment
      study, a series of rubidium compounds with different counter anions-acetate,
      bromide, carbonate, chloride, and fluoride-were orally administrated in a single
      dose to several groups of rats. Cumulative 24-h urine samples were obtained, and
      the levels of rubidium, fluoride, N-acetyl-beta-D-glucosaminidase and creatinine
      were measured to evaluate possible acute renal effects. Daily samples of serum
      were also obtained to determine the levels of aspartate and alanine
      aminotransferases to assess possible acute hepatic effects. Urinary rubidium
      excretion recovery of 8.0-10.5% shows that urine can be a useful diagnostic tool
      for rubidium exposure. The present results reveal that rubidium shows different
      biological effects depending on the counter anion. A pattern of large significant
      NAG leakage and elevation of ALT observed in rats treated with anhydrous rubidium
      fluoride indicates renal and hepatic toxicities that can be attributed to
      fluoride. The techniques reported in this study will be of help to assess the
      potential risks of toxicity of rubidium compounds with a variety of anions.

PMID- 24728876
TI  - Effect of Physalis peruviana L. on cadmium-induced testicular toxicity in rats.
AB  - Cadmium (Cd) stimulates the production of reactive oxygen species and causes
      tissue damage. We investigated here the protective effect of Physalis peruviana
      L. (family Solanaceae) against cadmium-induced testes toxicity in rats. Twenty
      eight Wistar albino rats were used. They were divided into four groups (n=7).
      Group 1 was used as control. Group 2 was intraperitoneally injected with 6.5
      mg/kg body weight (bwt) of cadmium chloride for 5 days. Group 3 was orally
      treated with 200 mg/kg bwt of methanolic extract of physalis (MEPh). Group 4 was
      pretreated with MEPh before cadmium for 5 days. Changes in body and testes
      weights were determined. Oxidative stress markers, antioxidant enzymes, and
      testosterone level were measured. Histopathological changes of testes were
      examined, and the immunohistochemical staining for the proapoptotic (caspase-3)
      protein was performed. The injection of cadmium caused a significant decrease in
      body weight, while a significant increase in testes weight and testes weight
      index was observed. Pretreatment with MEPh was associated with significant
      reduction in the toxic effects of Cd as shown by reduced testicular levels of
      malondialdehyde, nitric oxide, and caspase-3 expression and increased glutathione
      content, and the activities of superoxide dismutase, catalase, glutathione
      reductase, glutathione peroxidase, and testosterone were also increased.
      Testicular histopathology showed that Cd produced an extensive germ cell
      apoptosis, and the pretreatment of MEPh in Cd-treated rats significantly reduced
      Cd-induced testicular damage. On the basis of the above results, it can be
      hypothesized that P. peruviana L. has a protective effect against cadmium-induced
      testicular oxidative stress and apoptosis in the rat.

PMID- 24728874
TI  - Responsivity to familiar versus unfamiliar social reward in children with autism.
AB  - In autism spectrum disorders (ASD), social motivation theories suggest that the
      core social communication problems seen in children with ASD arise from
      diminished responsiveness to social reward. Although clinical and experimental
      data support these theories, the extent to which the reward deficit in ASD is
      unique for social rewards remains unclear. With the present investigation, we
      aimed to provide insight into the degree to which sociality as well as
      familiarity of reward incentives impact motivated goal-directed behavior in
      children with ASD. To do so, we directly compared the influence of familiar
      versus unfamiliar social reward relative to nonsocial, monetary reward in
      children with ASD relative to age- and IQ-matched typically developing controls
      (TDC) using a visual and auditory incentive go/nogo task with reward
      contingencies for successful response inhibitions. We found that children with
      ASD responded stronger to visual familiar and unfamiliar social reward as well as
      to nonsocial, monetary reward than TDC. While the present data are at odds with
      predictions made by social motivation theories, individual variations beyond
      clinical diagnosis, such as reward exposure across various social settings, help
      explain the pattern of results. The findings of this study stress the necessity
      for additional research on intra-individual as well as environmental factors that
      contribute to social reward responsiveness in individuals with ASD versus other
      neuropsychiatric disorders such as ADHD or conduct disorder. 

PMID- 24728877
TI  - Association between serum level of magnesium and postmenopausal osteoporosis: a
      meta-analysis.
AB  - There are conflicting reports as to the association between serum level of
      magnesium (Mg) and postmenopausal osteoporosis (OP). The purpose of the present
      study is to clarify the association between serum level of Mg and postmenopausal
      OP using a meta-analysis approach. We searched articles indexed in Pubmed and the
      Chinese Journal Full-text Database (CJFD) published as of October 2013 that met
      our predefined criteria. Seven eligible studies involving 1,349 postmenopausal
      women from 12 case-control study arms were identified. Overall, pooled analysis
      indicated that postmenopausal osteoporotic women had a lower serum level of Mg
      than the healthy controls (standardized mean difference [SMD]=-0.55, 95 %
      confidence interval [CI]=-0.83 to -0.26). Further subgroup analysis found a
      similar pattern in Turkey (SMD=-0.66, 95% CI=-0.99 to -0.32) and Belgium (SMD=
      0.98, 95% CI=-1.91 to -0.05), but not in China (SMD=0.02, 95% CI=-0.21 to 0.26).
      And the difference of serum level of Mg between postmenopausal osteoporotic women
      and healthy controls below the age of 60 years (SMD=-0.61, 95% CI=-1.09 to -0.13)
      was similar to that among the population over 60 years (SMD=-0.49, 95% CI=-0.80
      to -0.18).In conclusion, this meta-analysis suggests that the low serum level of
      Mg seems to be a risk factor for OP among the postmenopausal women. However, the
      subgroup analysis found that there was contradiction regarding races and
      geography, like China and Turkey. Thus, this finding needs further confirmation
      by trans-regional multicenter study to obtain better understanding of causal
      relationships between serum Mg and postmenopausal OP.

PMID- 24728878
TI  - "In sickness and in health": the peculiar occurrence of polymyalgia rheumatica in
      married cohabiting couples--a case series and review of the literature.
AB  - Polymyalgia rheumatica (PMR) is an inflammatory rheumatic disorder in elderly
      people. It is frequently associated with giant-cell arteritis (GCA), although it
      is still debated if they are the same disease or two distinct pathologies. The
      etiology of PMR remains challenging, although current knowledge supports the role
      of both genetic and environmental factors. Among these, there is evidence that
      infectious agents could trigger the disease's onset in some cases. We describe
      the peculiar case where PMR occurred in two Italian married and cohabiting
      couples and provide a review of the literature for similar cases. This is the
      first reported occurrence of PMR in two conjugal pairs in Italy. Moreover, in the
      second case, the wife presented PMR associated with GCA. To date, seven cases of
      PMR and two of GCA in married couples are described in the literature. The
      occurrence of PMR in both a husband and a wife supports the pathogenetic role of
      an environmental factor. 

PMID- 24728883
TI  - Anesthetic Management for Cardiopulmonary Bypass: Update for 2014.
AB  - Cardiopulmonary bypass has revolutionized the practice of cardiac surgery and
      allows safe conduct of increasingly complex cardiac surgery. A brief review of
      the bypass circuit is undertaken in this review. A more thorough review of the
      anesthetic management is accomplished including choice of anesthetic medications
      and their effects. The inflammatory response to cardiopulmonary bypass is
      reviewed along with interventions that may help ameliorate the inflammation. 

PMID- 24728879
TI  - Flow cytometry test to screen for HLA-B*58:01-associated allopurinol
      hypersensitivity.
AB  - A strong association between the human leucocyte antigen (HLA)-B*58:01 allele and
      allopurinol-associated severe cutaneous adverse reactions (SCAR) has been
      reported. A screening for HLA-B*58:01 before allopurinol has been suggested in
      guidelines for management of gout. HLA-B*58:01 screening is generally based on
      molecular biology methods that may be not suitable for wide application. We have
      retrospectively evaluated the performance on a rapid flow cytometry (FCM) test,
      based on the use of a monoclonal antibody specific for HLA-B17, an antigen that
      can be split into HLA-B*57 and -B*58 alleles by molecular biology testing, which
      is used to screen for HLA-B*57:01 before prescription of the antiretroviral agent
      abacavir in HIV-positive patients. Among 475 samples that were analysed by FCM
      and by molecular biology test as gold standard, 2 out of 89 false negative tests
      for HLA-B*58:01 were found. The sensitivity was 97.8% and the negative predictive
      value was 98.9%. We have shown that a FCM test can identify almost all HLA
      B*58:01 positive individuals. As FCM laboratories are more widely available than
      molecular biology ones, this approach could be used to reduce the risk for
      allopurinol-induced SCAR. Where both facilities are available, a two-step
      strategy (FCM as screening, molecular biology for confirmation) may reduce the
      cost of the screening.

PMID- 24728880
TI  - The impact of hepatitis screening on diagnosis and treatment in rheumatoid
      arthritis.
AB  - Identification of patients with exposure to viral hepatitis is an important part
      of the care of patients with inflammatory arthritis. This study was conducted to
      assess the extent of hepatitis B and C screening, and the prevalence of viral
      hepatitis in a cohort of patients with established rheumatoid arthritis (RA). The
      medical records of 100 consecutive RA patients were retrospectively analysed for
      screening of hepatitis B surface antigen, surface antibody and core antibody and
      hepatitis C antibody. A teaching session was then conducted with the rheumatology
      team, emphasising the rationale for viral hepatitis testing. We then
      prospectively analysed 100 more RA patients to see if hepatitis screening
      improved. In the initial 100 patients (21 % male, mean age 65 years), 85 % were
      taking methotrexate and 22 % biologic treatments. A complete hepatitis screen was
      present in 8 %, while 12 % had hepatitis B core antibody checked and 53 % had
      been tested for hepatitis C.The second cohort of patients was similar to the
      first in terms of demographics and treatment. A complete hepatitis screen was
      available in 63 %, while 65 % had hepatitis B core antibody checked and 81 % had
      been tested for hepatitis C.In total, we identified 4 new cases of positive
      hepatitis B core antibody, 11 cases of positive hepatitis B surface antibody and
      1 case of positive hepatitis C antibody. Even in populations where hepatitis B or
      C is non-endemic, screening will reveal new cases. Educational initiatives are
      helpful in teaching staff to screen patients.

PMID- 24728884
TI  - A Brief History of Cardiopulmonary Bypass.
AB  - The development and application of cardiopulmonary bypass (CPB) to permit open
      heart surgery is considered among the most important clinical advances in
      medicine during the last half of the 20th century. The birth of CPB for cardiac
      surgery is attributed to its first successful clinical use by John Gibbon Jr, 51
      years ago but its practical clinical use really began in the spring and summer of
      1955 when 2 groups led by John Kirklin at the Mayo Clinic and C Walton Lillehei
      at the University of Minnesota, initiated the routine use of CPB for open heart
      surgery. However, considerable developments were necessary and preceded the
      clinical accomplishment of CPB, and much has followed to make it the remarkably
      safe and effective procedure that it has become today. Many currently practicing
      cardiac anesthesiologists, cardiac surgeons, and perfusionists are unaware of how
      brief its history is and how much the practice of CPB has changed during its
      short existence. The aim of this article is to review this fascinating history
      and the lessons that can be learned from this review, and to indicate the
      opportunities that still exist for advancement. 

PMID- 24728885
TI  - Localisation and activation of the neurokinin 1 receptor in the enteric nervous
      system of the mouse distal colon.
AB  - The substance P neurokinin 1 receptor (NK1R) regulates motility, secretion,
      inflammation and pain in the intestine. The distribution of the NK1R is a key
      determinant of the functional effects of substance P in the gut. Information
      regarding the distribution of NK1R in subtypes of mouse enteric neurons is
      lacking and is the focus of the present study. NK1R immunoreactivity (NK1R-IR) is
      examined in whole-mount preparations of the mouse distal colon by indirect
      immunofluorescence and confocal microscopy. The distribution of NK1R-IR within
      key functional neuronal subclasses was determined by using established
      neurochemical markers. NK1R-IR was expressed by a subpopulation of myenteric and
      submucosal neurons; it was mainly detected in large multipolar myenteric neurons
      and was colocalized with calcitonin gene-related peptide, neurofilament M,
      choline acetyltransferase and calretinin. The remaining NK1R-immunoreactive
      neurons were positive for nitric oxide synthase. NK1R was expressed by most of
      the submucosal neurons and was exclusively co-expressed with vasoactive
      intestinal peptide, with no overlap with choline acetyltransferase. Treatment
      with substance P resulted in the concentration-dependent internalisation of NK1R
      from the cell surface into endosome-like structures. Myenteric NK1R was mainly
      expressed by intrinsic primary afferent neurons, with minor expression by
      descending interneurons and inhibitory motor neurons. Submucosal NK1R was
      restricted to non-cholinergic secretomotor neurons. These findings highlight key
      differences in the neuronal distribution of NK1R-IR between the mouse, rat and
      guinea-pig, with important implications for the functional role of NK1R in
      regulating intestinal motility and secretion. 

PMID- 24728886
TI  - Oleanolic acid derivatives induce apoptosis in human leukemia K562 cell involved
      in inhibition of both Akt1 translocation and pAkt1 expression.
AB  - Oleanolic acid (OA) derivatives exhibit numerous pleiotropic effects in many
      cancers. The present study aimed to investigate the molecular mechanisms of 5'
      amino-oleana-2,12-dieno[3,2-d]pyrimidin-28-oic acid (compound 4) and oleana-2,12
      dieno[2,3-d]isoxazol-28-oic acid (compound 5) inducing apoptosis in human
      leukemia K562 cell. We investigated the effects of the compounds on K562 cell
      growth, apoptosis and cell cycle. The compounds showed strong inhibitory effects
      on K562 cell viability in a dose-dependent manner determined by the 3-(4,5
      dimethylthiazoyl)-2,5-diphenyltetrazolium bromide assay and significantly
      increased chromatin condensation and apoptotic bodies in K562 cells. Flow
      cytometry assay suggested that the compounds induced inhibition of K562 cell
      proliferation associated with G1 phase arrest. In addition, the compounds
      inhibited Akt1 recruiting to membrane in CHO cells which express Akt1-EGFP
      constitutively and down-regulated the expression of pAkt1 in K562 cell. These
      results suggested that the compounds can efficiently inhibit proliferation and
      induce apoptosis perhaps involved in inactivation of Akt1. The OA derivatives may
      be potential chemotherapeutic agents for the treatment of human cancer. 

PMID- 24728887
TI  - An observational study: associations between nurse-reported hospital
      characteristics and estimated 30-day survival probabilities.
AB  - BACKGROUND: There is a growing body of evidence for associations between the work
      environment and patient outcomes. A good work environment may maximise healthcare
      workers' efforts to avoid failures and to facilitate quality care that is focused
      on patient safety. Several studies use nurse-reported quality measures, but it is
      uncertain whether these outcomes are correlated with clinical outcomes. The aim
      of this study was to determine the correlations between hospital-aggregated,
      nurse-assessed quality and safety, and estimated probabilities for 30-day
      survival in and out of hospital. METHODS: In a multicentre study involving almost
      all Norwegian hospitals with more than 85 beds (sample size=30, information about
      nurses' perceptions of organisational characteristics were collected. Subscales
      from this survey were used to describe properties of the organisations: quality
      system, patient safety management, nurse-physician relationship, staffing
      adequacy, quality of nursing and patient safety. The average scores for these
      organisational characteristics were aggregated to hospital level, and merged with
      estimated probabilities for 30-day survival in and out of hospital (survival
      probabilities) from a national database. In this observational, ecological study,
      the relationships between the organisational characteristics (independent
      variables) and clinical outcomes (survival probabilities) were examined. RESULTS:
      Survival probabilities were correlated with nurse-assessed quality of nursing.
      Furthermore, the subjective perception of staffing adequacy was correlated with
      overall survival. CONCLUSIONS: This study showed that perceived staffing adequacy
      and nurses' assessments of quality of nursing were correlated with survival
      probabilities. It is suggested that the way nurses characterise the microsystems
      they belong to, also reflects the general performance of hospitals.

PMID- 24728888
TI  - Computerised provider order entry combined with clinical decision support systems
      to improve medication safety: a narrative review.
AB  - BACKGROUND: Adverse drug events (ADEs) are a major cause of morbidity in
      hospitalised and ambulatory patients. Computerised provider order entry (CPOE)
      combined with clinical decision support systems (CDSS) are being widely
      implemented with the goal of preventing ADEs, but the effectiveness of these
      systems remains unclear. METHODS: We searched the specialised database Agency for
      Healthcare Research and Quality (AHRQ) Patient Safety Net to identify reviews of
      the effect of CPOE combined with CDSS on ADE rates in inpatient and outpatient
      settings. We included systematic and narrative reviews published since 2008 and
      controlled clinical trials published since 2012. RESULTS: We included five
      systematic reviews, one narrative review and two controlled trials. The existing
      literature consists mostly of studies of homegrown systems conducted in the
      inpatient setting. CPOE+CDSS was consistently reported to reduce prescribing
      errors, but does not appear to prevent clinical ADEs in either the inpatient or
      outpatient setting. Implementation of CPOE+CDSS profoundly changes staff
      workflow, and often leads to unintended consequences and new safety issues (such
      as alert fatigue) which limit the system's safety effects. CONCLUSIONS: CPOE+CDSS
      does not appear to reliably prevent clinical ADEs. Despite more widespread
      implementation over the past decade, it remains a work in progress.

PMID- 24728890
TI  - Delayed onset of rotatory self-motion perception, dysdiadochokinesia and
      disturbed eye pursuit caused by low-dose pregabalin.
AB  - A 30-year-old woman with chronic foot pain after an orthopaedic surgery and
      chronic neck pain presented to the emergency department (ED) with a history of
      self-rotatory vertigo with unsteadiness. She had started low-dose pregabalin, 25
      mg two times a day 9 months before experiencing symptoms with the dose gradually
      increased to 150 mg two times a day over this period. Clinical examination
      revealed difficulty performing eye pursuit with left eye and dysdiadochokinesia
      of the left arm. Owing to a suspicion of multiple sclerosis she underwent
      cerebral MRI, which was normal. Pregabalin was tapered over 2 months with a
      complete disappearance of the symptoms. We concluded that symptoms were due to
      pregabalin treatment. 

PMID- 24728889
TI  - Scurvy in an alcoholic patient treated with intravenous vitamins.
AB  - Vitamin C deficiency is rare in developed countries but there is an increased
      prevalence in chronic alcohol abusers. In the UK, it is common practice to treat
      patients with chronic alcoholism who are admitted to hospital with intravenous
      vitamins B1, B2, B3, B6 and C for 2-3 days, followed by oral thiamine and vitamin
      B-compound tablets. This is a case of a 57-year-old man with a history of chronic
      alcoholism and chronic obstructive lung disease who was admitted to the intensive
      care unit for pneumonia requiring ventilatory support. He was given high doses of
      intravenous vitamins B1, B2, B3, B6 and C for 3 days then oral thiamine and
      vitamin B compound tablets but developed scurvy 4 days later. He was restarted on
      oral vitamin C supplementation and showed signs of improvement within 3 days of
      treatment. 

PMID- 24728891
TI  - Parasitic infection of the male breast.
AB  - Breast lumps are commonly seen in clinical practice, yet deeper exploration of
      this particular case presented an unusual diagnostic challenge. 

PMID- 24728893
TI  - A rare obstetric emergency: acute uterine torsion in a 32-week pregnancy.
AB  - Uterine torsion is rare in pregnancy and the cause in most cases is unknown. It
      is associated with fetal compromise, with perinatal mortality reported to be
      around 12%. Our case describes an acute torsion, presenting in pregnancy with
      severe abdominal pain and vomiting with a viable 32-week gestation. Emergency
      caesarean section was performed and the 180 degrees  uterine torsion was
      diagnosed intraoperatively. Posterior hysterotomy was required for delivery prior
      to detorsion of the uterus. This report describes that prompt recognition and
      intraoperative vigilance can achieve a successful maternal and fetal outcome in
      this rare and difficult obstetric scenario. 

PMID- 24728892
TI  - Syringomyelia associated with inappropriate antidiuretic hormone secretion.
AB  - Hyponatraemia is the most common fluid-electrolyte disorder, and the most
      frequent related aetiologies are syndrome of inappropriate secretion of
      antidiuretic hormone (SIADH), which accounts for up to 38%. SIADH has been linked
      to multiple pathologies that affect the central nervous system; these disorders
      generally originate in the brain and, more rarely, in the spinal cord. It is
      often observed in patients undergoing neurosurgery and in patients with head
      injuries or intracranial tumours, and less common in those with spinal
      pathologies, especially traumatic. We describe an SIADH case associated with
      syringomyelia, in a patient admitted for severe, symptomatic hyponatraemia. 

PMID- 24728894
TI  - Can cycles of chills and fever resolve bipolar disorder mania?
AB  - Treatment resistance is common in populations of patients with bipolar disorder
      stressing the need for new therapeutic strategies. Favourable effects of fever on
      mental disease have been noted throughout history. Today there is increasing
      evidence that immunological processes are involved in the pathophysiology of
      mental disorders. We present a case in which a patient with treatment resistant
      bipolar disorder mania seemingly recovered as a result of recurrent fever. This
      indicates that artificial fever might become a last resort therapy for treatment
      resistant mania. 

PMID- 24728895
TI  - An unusual case of gout.

PMID- 24728896
TI  - Pulmonary sarcoidosis shortly after spinal tuberculosis infection: a diagnostic
      challenge.
AB  - Tuberculosis and sarcoidosis share similar histopathological findings. An
      aetiological connection between these diseases has been discussed. We report a
      case of pulmonary sarcoidosis, which occurred shortly after an isoniazid (INH)
      resistant spinal tuberculosis was diagnosed which was suspected to be a miliary
      tuberculosis. This report illustrates the need to sensitise clinicians to two
      possible important causes of lung parenchyma alterations under tuberculostatic
      therapy. 

PMID- 24728897
TI  - Histoplasmosis mimicking primary lung neoplasm.
AB  - A 70-year-old man, ex-smoker with a 3-pack-year smoking history, presented with a
      5-week history of persistent cough. There were no positive findings on clinical
      examination. The patient's chest X-ray showed a nodular density in the right
      lung, initially thought to be malignant. After an extensive workup which included
      CT-guided lung biopsies, bronchoscopies, positron emission tomography scanning,
      among many other investigations, discussion at the respiratory multidisciplinary
      team meeting, and a right upper lobe lung resection, a diagnosis of
      histoplasmosis was performed. 

PMID- 24728898
TI  - A bad shortcut: partial anomalous pulmonary venous return.

PMID- 24728899
TI  - Coexistence of giant cell fibroblastoma and encephalocele.
AB  - Giant cell fibroblastoma (GCF) is a rare soft tissue tumour that occurs almost
      exclusively in children younger than 10 years of age and is mostly located in the
      superficial soft tissues of the back and thighs. We present a rare case of GCF
      with encephalocele in a 1.5-year-old boy who presented with a swelling in the
      occipital area of the scalp since birth. CT scan suggested encephalocele without
      any suspicion of a mass lesion. On histopathology, an ill-defined proliferation
      of fibroblasts in a heavily collagenised and focally myxoid stroma was seen
      containing numerous multinucleated cells having a floret-like appearance along
      with mature glial tissue bordering a cystic space. Immunohistochemically, the
      stromal cells were positive for both, vimentin (diffuse) and CD34 (focal) thereby
      confirming the histological diagnosis of GCF. This case highlights the unusual
      coexistence of GCF with congenital defects and its histogenetic resemblance to
      dermatofibrosarcoma protuberans. 

PMID- 24728900
TI  - Nocturnal lagophthalmos: never seen before in hypernatraemic dehydration.
AB  - We present two cases in which a 10-month-old male infant and another 15-month-old
      female child presented with symptoms of sleeping with their eyes wide open
      (lagophthalmos) with features of gastroenteritis (GE) and dehydration. The first
      child had been seen and discharged the previous day from the paediatric emergency
      department (ED) with a diagnosis of GE. He presented the following day with
      sleeping discomfort with his eyes wide open and ongoing symptoms of GE. The
      second child presented to the ED with features of GE. She was found to be
      sleeping in the ED with her eyes wide open. Investigations of both children
      revealed hypernatraemic dehydration. Correction of the electrolyte imbalance in
      both cases over a period of 48 h led to the resolution of symptoms. 

PMID- 24728901
TI  - Extensive intracranial involvement with multiple dissections in a case of giant
      cell arteritis.
AB  - A 56-year-old man presented with weight loss, articular pain and minor
      neurological symptoms progressing over 1 month. Neurosonological evaluation
      suggested occlusion in intracranial segments of the left vertebral artery (VA)
      and of both internal carotid arteries (ICA) and hypoechoic halo sign in both
      superficial temporal arteries. The diagnosis of giant cell arteritis was
      supported by inflammatory markers and confirmed by biopsy. Despite early steroid
      initiation, he manifested fluctuant vascular deficits and became lethargic. Brain
      MRI indicated watershed infarcts and intracranial dissections of left VA and both
      ICA. The patient was stabilised with the association of prednisolone 2 mg/kg,
      methotrexate and oral anticoagulation. Since then he has been neurologically
      asymptomatic and control imaging showed only residual intracranial left VA
      stenosis, with no signs of temporal artery inflammation or new vascular lesions.
      This is to the best of our knowledge, the first reported clinical case with such
      an extensive intracranial involvement with multiple dissections. 

PMID- 24728902
TI  - Younger females are at greater risk of vasodilation-related adverse symptoms
      caused by dihydropyridine calcium channel blockers: results of a study of 11,918
      Japanese patients.
AB  - BACKGROUND AND OBJECTIVE: Adequate control of blood pressure in younger females
      is of crucial importance, because they are at higher risk of hypertensive target
      organ damage compared with males of similar age. In addition, female sex is a
      risk factor for adverse effects of antihypertensive drugs, especially
      dihydropyridines. This study set out to assess the incidence of adverse reactions
      during dihydropyridine use in a real-life clinical setting, focusing on the
      influence of female sex and age. METHODS: The incidence of adverse reactions to
      dihydropyridine calcium channel blockers were investigated in 11,918 Japanese
      patients who participated in the Drug Event Monitoring project of the Japan
      Pharmaceutical Association conducted in Kumamoto prefecture. A multiple logistic
      regression analysis was used to determine the association between the incidence
      of adverse symptoms and female sex, with adjusted odds ratios (ORs) and 95%
      confidence intervals (95% CIs). RESULTS: Vasodilation-related adverse symptoms
      occurred significantly more often in females than in males (OR 1.87, 95% CI 1.28
      2.71, p=0.001). Furthermore, among females only, the younger age group (<50
      years) complained of vasodilation-related symptoms more frequently (OR 2.39, 95%
      CI 1.02-5.59, p=0.045) and the older age group (>=80 years) complained of
      vasodilation-related symptoms less frequently (OR 0.56, 95% CI 0.33-0.95,
      p=0.030) than the middle age group (50-79 years). CONCLUSION: To the best of our
      knowledge, this is the first report showing that younger females are at high risk
      for vasodilation-related adverse symptoms during dihydropyridine use in a real
      life clinical setting. These results should be verified in clinical studies using
      larger samples of young patients and more parameters.

PMID- 24728904
TI  - Continual naringin treatment benefits the recovery of traumatic brain injury in
      rats through reducing oxidative and inflammatory alterations.
AB  - Naringin is neuroprotective in ischemia and other disease models. However, the
      effects of naringin are unknown after traumatic brain injury (TBI). The present
      study explored the role of naringin for neuroprotection in TBI rats. TBI was
      performed with the weight drop technique, and naringin was given orally at a dose
      of 100 mg/kg/day. The neurological scores, tissue edema, and oxidative
      stress/inflammation parameters [malondialdehyde (MDA), superoxide dismutase,
      nitric oxide, inducible nitric oxide synthase (iNOS), as well as interleukin
      1beta (IL-1beta)] were measured. Compared to sham controls, TBI rats displayed
      obvious sensorimotor dysfunction, significant brain edema, and elevated oxidative
      and inflammatory molecules. Although a 7-day pre-treatment of naringin was unable
      to reverse these pathological changes, a 14-day continual treatment (7 days
      before and 7 days after the TBI) attenuated the increases in MDA and nitric
      oxide; enhanced the activation of superoxide dismutase; depressed the over
      activation of iNOS; down-regulated the over-expression of IL-1beta; and reduced
      the cortex edema. Additionally, the TBI-induced behavioral dysfunction was
      reduced. These results suggest that naringin treatment can attenuate cellular and
      histopathological alterations and improve the sensorimotor dysfunction of TBI
      rats, which may be partly due to the attenuation of oxidative and inflammatory
      damages. 

PMID- 24728906
TI  - The quality of carp (Cyprinus carpio L.) cultured in various Polish regions.
AB  - BACKGROUND: Although environmental factors greatly affect the quality of carp
      meat, no regulations impose labelling the place of cultivation of freshwater
      fish. That is why the purpose of this study was to determine the quality of carp
      meat cultivated in several regions of Poland as well as to assess the necessity
      of implementing such regulations. RESULTS: The influence of the cultivation
      region on colour, nutrition value, health safety and sensory quality of carp meat
      was assessed. The analysis included colour measurement, determination of fatty
      acid profile and sensory evaluation of carp muscle. Moreover, microbiological
      analysis of the fish surface was performed. The results show that the place of
      cultivation does not influence the lightness (L*) of fillet, but has an impact on
      other colour parameters (a*, b*). The microbiological quality of fish from all
      studied farms was satisfactory, since no pathogenic microorganisms were observed
      on the fish surface. The fatty acid profile was fairly varied (P < 0.01),
      depending on the place of cultivation. CONCLUSION: Since final results seem
      ambiguous, further analyses of quality features of carp from various regions and
      cultures should be performed, before any recommendation for the necessity of
      labelling the place and method of cultivation should be suggested.

PMID- 24728905
TI  - Duodenal-Jejunal bypass improves glucose homeostasis in association with
      decreased proinflammatory response and activation of JNK in the liver and adipose
      tissue in a T2DM rat model.
AB  - BACKGROUND: There is accumulating evidence that obesity leads to a
      proinflammatory state, which plays crucial roles in insulin resistance and
      development of type 2 diabetes mellitus (T2DM). Previous studies demonstrated
      that weight loss after bariatric surgery was accompanied by a suppression of the
      proinflammatory state. However, the effect of bariatric surgery on the
      proinflammatory state and associated signaling beyond weight loss is still
      elusive. The objective of this study was to investigate the effect of duodenal
      jejunal bypass (DJB) on glucose homeostasis, the proinflammatory state and the
      involving signaling independently of weight loss. METHODS: A high-fat diet and
      low-dose streptozotocin administration were used to induce T2DM in male Sprague
      Dawley rats. The diabetic rats underwent DJB or sham surgery. The blood glucose,
      glucose tolerance and insulin resistance were determined to evaluate the glucose
      homeostasis. Serum insulin, GLP-1 and hsCRP were detected by ELISA. The gene
      expression of TNF-alpha, IL-6, IL-1beta and MCP-1 in liver and fat was determined
      by quantitative real-time RT-PCR. The JNK activity and serine phosphorylation of
      IRS-1 in liver and adipose tissue were determined by Western blotting. RESULTS:
      Compared to the S-DJB group, DJB induced significant and sustained glycemic
      control with improved insulin sensitivity and glucose tolerance independently of
      weight loss. DJB improved the proinflammatory state indicated by decreased
      circulating hsCRP and proinflammatory gene expression in the liver and adipose
      tissue. The JNK activity and serine phosphorylation of IRS-1 in liver and adipose
      tissue were significantly reduced after DJB. CONCLUSIONS: DJB achieved a rapid
      and sustainable glycemic control independently of weight loss. The data indicated
      that the improved proinflammatory state and decreased JNK activity after DJB may
      contribute to the improved glucose homeostasis.

PMID- 24728903
TI  - Dihydromyricetin ameliorates behavioral deficits and reverses neuropathology of
      transgenic mouse models of Alzheimer's disease.
AB  - Alzheimer's disease (AD) is the leading progressive neurodegenerative disorder
      afflicting 35.6 million people worldwide. There is no therapeutic agent that can
      slow or stop the progression of AD. Human studies show that besides loss of
      cognition/learning ability, neuropsychological symptoms such as anxiety and
      seizures are seen as high as 70 and 17 % respectively in AD patients, suggesting
      dysfunction of GABAergic neurotransmission contributes to pathogenesis of AD.
      Dihydromyricetin (DHM) is a plant flavonoid and a positive allosteric modulator
      of GABAARs we developed recently (Shen et al. in J Neurosci 32(1):390-401, 2012
      [1]). In this study, transgenic (TG2576) and Swedish transgenic (TG-SwDI) mice
      with AD-like pathology were treated with DHM (2 mg/kg) for 3 months.
      Behaviorally, DHM-treated mice show improved cognition, reduced anxiety level and
      seizure susceptibility. Pathologically, DHM has high efficacy to reduce amyloid
      beta (Abeta) peptides in TG-SwDI brain. Further, patch-clamp recordings from
      dentate gyrus neurons in hippocampal slices from TG-SwDI mice showed reduced
      frequency and amplitude of GABAAR-mediated miniature inhibitory postsynaptic
      currents, and decreased extrasynaptic tonic inhibitory current, while DHM
      restored these GABAAR-mediated currents in TG-SwDI. We found that gephyrin, a
      postsynaptic GABAAR anchor protein that regulates the formation and plasticity of
      GABAergic synapses, decreased in hippocampus and cortex in TG-SwDI. DHM treatment
      restored gephyrin levels. These results suggest that DHM treatment not only
      improves symptoms, but also reverses progressive neuropathology of mouse models
      of AD including reducing Abeta peptides, while restoring gephyrin levels,
      GABAergic transmission and functional synapses. Therefore DHM is a promising
      candidate medication for AD. We propose a novel target, gephyrin, for treatment
      of AD. 

PMID- 24728912
TI  - Symbolic extensions applied to multiscale structure of genomes.
AB  - A genome of a living organism consists of a long string of symbols over a finite
      alphabet carrying critical information for the organism. This includes its
      ability to control post natal growth, homeostasis, adaptation to changes in the
      surrounding environment, or to biochemically respond at the cellular level to
      various specific regulatory signals. In this sense, a genome represents a
      symbolic encoding of a highly organized system of information whose functioning
      may be revealed as a natural multilayer structure in terms of complexity and
      prominence. In this paper we use the mathematical theory of symbolic extensions
      as a framework to shed light onto how this multilayer organization is reflected
      in the symbolic coding of the genome. The distribution of data in an element of a
      standard symbolic extension of a dynamical system has a specific form: the
      symbolic sequence is divided into several subsequences (which we call layers)
      encoding the dynamics on various "scales". We propose that a similar structure
      resides within the genomes, building our analogy on some of the most recent
      findings in the field of regulation of genomic DNA functioning. 

PMID- 24728914
TI  - Kinin B1 receptor regulates interactions between neutrophils and endothelial
      cells by modulating the levels of Mac-1, LFA-1 and intercellular adhesion
      molecule-1.
AB  - Kinins are pro-inflammatory peptides that mimic the cardinal features of
      inflammation. We examined the concept that expression levels of endothelial
      intercellular adhesion molecule-1 (ICAM-1) and neutrophil integrins Mac-1 and LFA
      1 are modulated by the kinin B1 receptor (B1R) agonist, Lys-des[Arg(9)]bradykinin
      (LDBK). Stimulation of endothelial cells with LDBK increased the levels of ICAM-1
      mRNA transcripts/protein, and also of E-selectin and platelet endothelial
      adhesion molecule-1. ICAM-1 levels increased in a magnitude comparable with that
      produced by TNF-alpha. This stimulatory effect was reduced when endothelial
      cells, which had been previously transfected with a B1R small interfering RNA,
      were stimulated with LDBK, under comparable conditions. Similarly, LDBK produced
      a significant increase in protein levels of LFA-1 and Mac-1 integrins in human
      neutrophils, an effect that was reversed by pretreatment of cells with 10 ug/ml
      cycloheximide or a B1R antagonist. Functional experiments performed with post
      confluent monolayers of endothelial cells stimulated with LDBK and neutrophils
      primed with TNF-alpha, and vice versa, resulted in enhanced adhesiveness between
      both cells. Neutralizing Abs to ICAM-1 and Mac-1 reduced the adhesion between
      them. Our results indicate that kinin B1R is a novel modulator that promotes
      adhesion of leukocytes to endothelial cells, critically enhancing the movement of
      neutrophils from the circulation to sites of inflammation. 

PMID- 24728915
TI  - The association of idiopathic recurrent early pregnancy loss with polymorphisms
      in folic acid metabolism-related genes.
AB  - The aim of this study was to investigate the association between polymorphisms in
      folic acid metabolism-related genes and idiopathic recurrent early pregnancy loss
      (REPL). A prospective case-control study was performed on a cohort of 82 REPL
      patients and 166 healthy controls. Genotyping of methylenetetrahydrofolate
      reductase (MTHFR) C677T and A1298C was assessed by applying polymerase chain
      reaction for amplification followed by DNA sequencing, for methionine synthase
      reductase A66G, solute carrier family 19, member 1 (SLC19A1) G80A and C696T, and
      genotyping was done by utilizing the Sequenom MassARRAY system. The results
      revealed a significant association between MTHFR A1298C polymorphism and
      idiopathic REPL. Haplotype analysis indicated that the MTHFR 677C-MTHFR 1298C
      allele combination was associated with REPL (P < 0.001). The MTHFR 677C-MTHFR
      1298A and SLC19A1 80G-SLC19A1 696C allele combinations had lower frequencies in
      patients with REPL, but with P > 0.05 (P = 0.093 and P = 0.084, respectively). 

PMID- 24728924
TI  - Human exposure to metals: levels in autopsy tissues of individuals living near a
      hazardous waste incinerator.
AB  - The concentrations of a number of metals were determined in the brain, bone,
      kidney, liver, and lung of 20 autopsied subjects who had lived, at least 10
      years, in the neighborhood of a hazardous waste incinerator (HWI) in Tarragona
      (Catalonia, Spain). Results were compared with those obtained in 1998 (baseline
      survey) and previous surveys (2003 and 2007). Arsenic, Be, Ni, Tl, and V showed
      concentrations below the corresponding detection limits in all tissues. Cadmium
      showed the highest levels in the kidney, with a mean value of 21.15 MUg/g.
      However, Cd was found below the detection limit in the brain and bone. Chromium
      showed similar concentrations in the kidney, brain, and lung (range of mean
      values, 0.57-0.66 MUg/g) and higher in the bone (1.38 MUg/g). In turn, Hg was
      below the detection limit in all tissues with the exception of the kidney, where
      the mean concentration was 0.15 MUg/g (range, <0.05-0.58 MUg/g). On the other
      hand, Mn could be detected in all tissues showing the highest levels in the liver
      and kidney (1.45 and 1.09 MUg/g, respectively). Moreover, Pb showed the highest
      concentrations in bone (mean, 1.39 MUg/g; range, <0.025-4.88 MUg/g). Finally, Sn
      could be detected only in some tissue samples, reaching the highest values in the
      bone (0.17 MUg/g). The current metal levels in human tissues from individuals
      living near the HWI of Tarragona are comparable and of a similar magnitude to
      previously reported results corresponding to general populations, as well as
      those of our previous surveys. 

PMID- 24728925
TI  - Sensing cellular states--signaling to chromatin pathways targeting Polycomb and
      Trithorax group function.
AB  - Cells respond to extra- and intra-cellular signals by dynamically changing their
      gene expression patterns. After termination of the original signal, new
      expression patterns are maintained by epigenetic DNA and histone modifications.
      This represents a powerful mechanism that enables long-term phenotypic adaptation
      to transient signals. Adaptation of epigenetic landscapes is important for
      mediating cellular differentiation during development and allows adjustment to
      altered environmental conditions throughout life. Work over the last decade has
      begun to elucidate the way that extra- and intra-cellular signals lead to changes
      in gene expression patterns by directly modulating the function of chromatin
      associated proteins. Here, we review key signaling-to-chromatin pathways that are
      specifically thought to target Polycomb and Trithorax group complexes, a classic
      example of epigenetically acting gene silencers and activators important in
      development, stem cell differentiation and cancer. We discuss the influence that
      signals triggered by kinase cascades, metabolic fluctuations and cell-cycle
      dynamics have on the function of these protein complexes. Further investigation
      into these pathways will be important for understanding the mechanisms that
      maintain epigenetic stability and those that promote epigenetic plasticity. 

PMID- 24728926
TI  - Salubrinal, ER stress inhibitor, attenuates kainic acid-induced hippocampal cell
      death.
AB  - Kainic acid (KA)-induced neuronal death is closely linked to endoplasmic
      reticulum (ER) and mitochondrial dysfunction. Parkin is an ubiquitin E3 ligase
      that mediates the ubiquitination of the Bcl-2 family of proteins and its
      mutations are associated with neuronal apoptosis in neurodegenerative diseases.
      We investigated the effect of salubrinal, an ER stress inhibitor, on the
      regulation of ER stress and mitochondrial apoptosis induced by KA, in particular,
      by controlling parkin expression. We showed that salubrinal significantly reduced
      seizure activity and increased survival rates of mice with KA-induced seizures.
      We found that salubrinal protected neurons against apoptotic death by reducing
      expression of mitochondrial apoptotic factors and elF2alpha-ATF4-CHOP signaling
      proteins. Interestingly, we showed that salubrinal decreased the KA-induced
      parkin expression and inhibited parkin translocation to mitochondria, which
      suggests that parkin may regulate a cross-talk between ER and mitochondria.
      Collectively, inhibition of ER stress attenuates mitochondrial apoptotic and ER
      stress pathways and controls parkin-mediated neuronal death following KA-induced
      seizures. 

PMID- 24728927
TI  - Interference between concurrent resistance and endurance exercise: molecular
      bases and the role of individual training variables.
AB  - Concurrent training is defined as simultaneously incorporating both resistance
      and endurance exercise within a periodized training regime. Despite the potential
      additive benefits of combining these divergent exercise modes with regards to
      disease prevention and athletic performance, current evidence suggests that this
      approach may attenuate gains in muscle mass, strength, and power compared with
      undertaking resistance training alone. This has been variously described as the
      interference effect or concurrent training effect. In recent years, understanding
      of the molecular mechanisms mediating training adaptation in skeletal muscle has
      emerged and provided potential mechanistic insight into the concurrent training
      effect. Although it appears that various molecular signaling responses induced in
      skeletal muscle by endurance exercise can inhibit pathways regulating protein
      synthesis and stimulate protein breakdown, human studies to date have not
      observed such molecular 'interference' following acute concurrent exercise that
      might explain compromised muscle hypertrophy following concurrent training.
      However, given the multitude of potential concurrent training variables and the
      limitations of existing evidence, the potential roles of individual training
      variables in acute and chronic interference are not fully elucidated. The present
      review explores current evidence for the molecular basis of the specificity of
      training adaptation and the concurrent interference phenomenon. Additionally,
      insights provided by molecular and performance-based concurrent training studies
      regarding the role of individual training variables (i.e., within-session
      exercise order, between-mode recovery, endurance training volume, intensity, and
      modality) in the concurrent interference effect are discussed, along with the
      limitations of our current understanding of this complex paradigm. 

PMID- 24728929
TI  - Functional analysis reveals angiogenic potential of human mesenchymal stem cells
      from Wharton's jelly in dermal regeneration.
AB  - Disorders in skin wound healing are a major health problem that requires the
      development of innovative treatments. The use of biomaterials as an alternative
      of skin replacement has become relevant, but its use is still limited due to poor
      vascularization inside the scaffolds, resulting in insufficient oxygen and growth
      factors at the wound site. In this study, we have developed a cell-based wound
      therapy consisting of the application of collagen-based dermal scaffolds
      containing mesenchymal stem cells from Wharton's jelly (WJ-MSC) in an
      immunocompetent mouse model of angiogenesis. From our comparative study on the
      secretion profile between WJ-MSC and adipose tissue-derived MSC, we found a
      stronger expression of several well-characterized growth factors, such as VEGF-A,
      angiopoietin-1 and aFGF, which are directly linked to angiogenesis, in the
      culture supernatant of WJ-MSC, both on monolayer and 3D culture conditions. WJ
      MSC proved to be angiogenic both in vitro and in vivo, through tubule formation
      and CAM assays, respectively. Moreover, WJ-MSC consistently improved the healing
      response in vivo in a mouse model of human-like dermal repair, by triggering
      angiogenesis and further providing a suitable matrix for wound repair, without
      altering the inflammatory response in the animals. Since these cells can be
      easily isolated, cultured with high expansion rates and cryopreserved, they
      represent an attractive stem cell source for their use in allogeneic cell
      transplant and tissue engineering.

PMID- 24728928
TI  - The efficacy of acute nutritional interventions on soccer skill performance.
AB  - BACKGROUND: The use of nutritional ergogenic aids in team sports such as soccer
      is now commonplace. Aligned with the primary aim of soccer, which is to score
      more goals than the opposition within the allotted time, the quality of
      performance of technical actions (i.e., skills) executed during soccer-specific
      exercise is likely to determine success. However, when seeking to maintain soccer
      skill performance, information about the efficacy of nutritional interventions is
      lacking and factors which might modulate the efficacy of such strategies are
      unclear. OBJECTIVE: This review aimed (i) to systematically evaluate the current
      research that examines the efficacy of nutritional interventions on soccer
      skills, and (ii) to provide a qualitative commentary on factors that have the
      potential to modulate the efficacy of such strategies. DATA SOURCES: Relevant
      databases (PubMed and SPORTDiscus) were searched up to and including 1 July, 2013
      for studies that investigated the efficacy of acute nutritional interventions on
      soccer skill performances. STUDY SELECTION: Overall, 279 records were retrieved.
      Articles were sequentially excluded from the review based on specific criteria,
      being: (A) articles that did not report outcomes directly relating to skilled
      performances in soccer, (B) articles that examined the influence of interventions
      that were not nutritional in origin and/or were nutritional in origin but
      provided >3 hours before skill testing commenced, (C) articles that were review
      papers, and (D) post-acceptance withdrawal of articles methods from database.
      STUDY APPRAISAL AND SYNTHESIS METHODS: Articles were independently assessed for
      the quality of the methods employed based upon the Physiotherapy Evidence
      Database (PEDro) scale. Records achieving a minimum PEDro score of 5 out of 10
      were included in this review. Qualitative appraisal of 13 articles was performed
      after the application of exclusion criteria and quality assurance processes. The
      majority (n = 8) of articles examined the influence of carbohydrates on technical
      performance whereas fewer studies investigated the influence of caffeine
      ingestion (n = 2) and fluid provision (n = 3). RESULTS: Findings were reported
      for a total of 171 participants and all but one of the included articles used
      cross-over study designs. Most participants (94 %) were male, highly trained
      (reported maximal aerobic capacity range 50-59 ml.kg(-1).min(-1)) and exercised
      in temperate environments (reported temperature range 13-25  degrees C). Six of
      the eight studies reported that carbohydrates, consumed in the form of a 6-8 %
      solution of glucose, sucrose or maltodextrin at rates of 30-60 g.h(-1), enhanced
      at least one aspect of skilled performance over the duration of exercise (75-90
      min). Although some evidence exists to support the consumption of caffeine (6
      mg.kg(-1) body mass [BM]) and prescribed fluid to preserve skills performed
      during soccer-specific exercise, findings from the small number of included
      studies were inconsistent. LIMITATIONS: The outcome measures and methods used to
      quantify skilled performance were not consistent across studies; consequently, it
      was not possible to perform meta-analyses to produce pooled effect sizes in this
      review. CONCLUSIONS: The findings from this systematic review suggest that
      nutritional interventions, which provide carbohydrate, caffeine and fluid, have
      potential to preserve skills performed under conditions that induce soccer
      specific fatigue. The weight of current evidence supports the consumption of
      carbohydrate, but is less conclusive with respect to caffeine and fluid
      provision. It is likely that the efficacy of a nutritional intervention will be
      modulated by factors including the dose consumed, the mode of administration,
      individual responsiveness to the intervention and interactions with other
      physiological changes occurring during soccer-specific exercise. Consequently,
      these factors should be considered when using carbohydrates, caffeine and fluid
      provision to maintain skilled performances in soccer. Future research should seek
      to optimise the nutritional strategies employed to maintain technical performance
      throughout match-play.

PMID- 24728931
TI  - Development of an automated multi-injection shotgun lipidomics approach using a
      triple quadrupole mass spectrometer.
AB  - Shotgun lipidomics is a well-suited approach to monitor lipid alterations due to
      its ability to scan for varying lipid types on a global, class and individual
      species level. However, the ability to perform high-throughput shotgun lipidomics
      has remained challenging due to time-consuming data processing and hardware
      limitations. To increase the throughput nature of shotgun lipidomics, an
      automated shotgun lipidomics approach is described utilizing conventional low
      flow gradient liquid chromatography (LC) analysis (post-injection) coupled with
      multiple sample injections per sample (on a lipid scan per injection basis). The
      proposed automated multi-injection approach resulted in a reproducible lipid
      scanning period of 2.5 min (in a 4.5 min total data acquisition period), thereby
      providing a sufficient scanning period for performing either mass spectrometric
      or tandem mass spectrometric analyses. In addition to being simple, robust and
      reproducible, this approach was also constructed to be cost-effective by using
      common LC instrumentation and customizable as the data acquisition period can be
      tailored to perform different scan types, period lengths and scan numbers.
      Combined with a strategy to create multiple lipid-specific aliquots per sample,
      the overall approach provides a simple and efficient platform to perform high
      throughput lipid profiling.

PMID- 24728932
TI  - Protective effect of (-)-epigallocatechin-3-gallate on capsaicin-induced DNA
      damage and oxidative stress in human erythrocyes and leucocytes in vitro.
AB  - The aim of this study is to show that protective effects of the main catechin (-)
      epigallocatechin-3-gallate (EGCG) against capsaicin (CAP) induced oxidative
      stress and DNA damage in human blood in vitro. Superoxide dismutase, catalase,
      glutathione peroxidase and malondialdehyde (MDA) level were studied in
      erythrocytes and leucocytes with increased concentrations of CAP. DNA damage in
      leucocytes was measured by the comet assay. Human blood cells have been
      administered with doses between 0 and 200 MUM of CAP and/or EGCG (20 MUM) for an
      hour at 37  degrees C. Treatment with CAP alone has increased the levels of MDA
      and decreased antioxidant enzymes in human blood cells. A significant increase in
      tail DNA%, mean tail length and tail moment indicating DNA damage has been
      observed at the highest dose of CAP treatment when compared to controls.
      Treatment of cells with CAP plus EGCG prevented CAP-induced changes in
      antioxidant enzyme activities and MDA level and mean tail lenght indicating DNA
      damage. A significant increase in mean tail lenght was observed at high doses of
      CAP. These data suggest that EGCG can prevent toxicity to human erythrocytes and
      leucocytes caused by CAP, only at low doses. 

PMID- 24728933
TI  - Workplace sex composition and ischaemic heart disease: A longitudinal analysis
      using Swedish register data.
AB  - AIMS: The aim of this study is to follow-up on previous research indicating that
      the sex composition of workplaces is related to a number of health outcomes,
      including sickness absenteeism and mortality. We test two hypotheses. The first
      is Kanter's theory of tokenism, which suggests that minority group members suffer
      from an increased risk of stress. Secondly, we test the hypothesis that
      workplaces with a higher proportion of men will have a higher incidence rate of
      ischaemic heart disease (IHD), as men are more likely to engage in negative
      health behaviours, and through peer effects this will result in a workplace
      culture that is detrimental to health over the long term. METHODS: Large-scale,
      longitudinal Swedish administrative register data are used to study the risk of
      overnight hospitalization for IHD amongst 67,763 men over the period 1990 to
      2001. Discrete-time survival analyses were estimated in the form of logistic
      regression models. RESULTS: Men have an elevated risk of suffering from IHD in
      non-gender-balanced workplaces, but this association was only statistically
      significant in workplaces with 61-80% and 81-100% males. However, after adjusting
      for occupation no clear pattern of association could be discerned. No pattern of
      association was observed for women. CONCLUSIONS: This study suggests that the
      gender composition of workplaces is not strongly associated with the risk of
      suffering from IHD.

PMID- 24728934
TI  - Temporal changes in the attitude towards smoking bans in public arenas among
      adults in the Capital Region of Denmark from 2007 to 2010.
AB  - AIM: The population's attitude towards smoking bans in public arenas is important
      for their passing, implementation and compliance. Smoking bans are believed to
      reduce the social acceptability of smoking, and once people experience them,
      public support increases--also among pre-ban sceptics. This study aimed to
      examine the temporal changes in public attitude towards smoking bans in public
      arenas from 2007 to 2010 and whether these changes differed across educational
      attainment, smoking status and intention to quit among smokers. METHODS: Data
      from two surveys among adults (aged 25-79 years) in 2007 and 2010 in the Capital
      Region of Denmark (n=36,472/42,504, response rate = 52.3) was linked with data on
      sex, age and educational attainment from central registers. Age-standardised
      prevalence of supportive attitude towards smoking bans was estimated. Temporal
      changes in supportive attitude were explored in workplaces, restaurants and bars
      using logistic regression models. RESULTS: The prevalence of supportive attitude
      towards smoking bans increased significantly in all arenas from 2007 to 2010.
      Positive temporal changes in supportive attitude towards smoking bans were seen
      across educational attainment, smoking status and intention to quit smoking in
      restaurants and across smoking status for smoking bans in workplaces and bars.
      CONCLUSIONS: The results of this study show that the public's attitude towards
      smoking in public arenas has changed after the implementation of a comprehensive
      smoking ban. This change in attitude can support implementation of future
      legislation on smoking and may lead to positive changes in smoking norms.

PMID- 24728938
TI  - Inflammation and Coagulation as Mediators in the Relationships Between Religious
      Attendance and Functional Limitations in Older Adults.
AB  - OBJECTIVE: The aim of this study was to examine inflammation and coagulation,
      which are positively linked to disability and inversely linked to increased
      religious attendance, as mediators in the cross-sectional relationships between
      religious attendance and functional status. METHOD: Frequency of attendance and
      limitations in basic activities of daily living (ADLs), instrumental activities
      (IADLs), and mobility were assessed in 1,423 elders. RESULTS: More frequent
      attendance was associated with fewer ADL, IADL, and mobility limitations, and
      with lower levels of inflammation and coagulation including interleukin-6,
      soluble vascular cell adhesion molecule, and D-dimer. Inflammation and
      coagulation partially mediated the associations between attendance and function.
      Eight percent of the effect of attendance on ADL (p = .014), 5% of the effect on
      IADL (p = .003), and 8% of the effect on mobility (p = .001) limitations were due
      to inflammation and coagulation. DISCUSSION: Relationships between attendance and
      function may be due in part to lower levels of inflammation and coagulation among
      elders who attend services.

PMID- 24728939
TI  - Establishing a pharmacy presence in the emergency department: opportunities and
      challenges in the French setting.
AB  - Overview of clinical pharmacy practice around the world shows that pharmaceutical
      services in emergency departments (EDs) are far less common in Europe than in
      North America. Reported experiences have shown the impact of a clinical pharmacy
      service on drug utilisation and safety issues. This commentary presents the
      implementation of a pharmacy presence in the ED of a French tertiary care
      hospital. Our experience helps to define the role of the clinical pharmacist in
      the ED, including patient interviewing, providing medication reconciliation,
      promoting drug safety, and supporting specific interventions to improve quality
      of care and patient safety. The role of ED pharmacists in the improvement of
      quality of care is not necessarily limited to drug therapy, e.g. by helping
      outpatients to access care and treatment facilities as best suits their needs.
      Challenges of implementing ED pharmacy services have been identified well, but
      still require developing strategies to be overcome. 

PMID- 24728940
TI  - Viral transduction of primary Schwann cells using a Cre-lox system to regulate
      GDNF expression.
AB  - Glial cell-line-derived neurotrophic factor (GDNF) is a potent neurotrophic
      factor known to enhance motor nerve regeneration following its delivery. However,
      recent studies have determined that extended GDNF delivery to regenerating axons
      can entrap motor axons at the site of GDNF delivery. This entrapment leads to
      reduced motor axons available to reinnervate muscle. To address this issue, we
      designed a cell-based GDNF expression system that can temporally regulate protein
      expression using an inducible gene excision mechanism to prevent entrapment at
      the site of expression. To design this system for regulation of GDNF expression,
      we transduced two lentiviral vectors, one containing a constitutively active GDNF
      transgene flanked by two loxP sites, and the other containing a tetracycline
      inducible cre transgene along with its constitutively active transactivator, into
      Schwann cells (SCs). These SCs over-express GDNF, but expression can be
      suppressed through the administration of tetracycline family antibiotics, such as
      doxycycline. The engineered SCs produced significantly more GDNF as compared to
      untransduced controls, as measured by enzyme-linked immunosorbent assay (ELISA).
      Following doxycycline treatment, these SCs produced significantly lower levels of
      GDNF and induced less neurite extension as compared to untreated SCs. Engineered
      SCs treated with doxycycline showed a marked increase in Cre recombinase
      expression, as visualized by immunohistochemistry (IHC), providing evidence of a
      mechanism for the observed changes in GDNF expression levels and biological
      activity. This cell-based GDNF expression system could have potential for future
      in vivo studies to provide a temporally controlled GDNF source to promote axon
      growth.

PMID- 24728942
TI  - Development of a new wheat germplasm with high anther culture ability by using a
      combination of gamma-ray irradiation and anther culture.
AB  - BACKGROUND: Wheat with high anther culture ability would be beneficial for
      breeding. We aimed to screen a wheat germplasm to with high anther culture
      ability as well as good agronomic characteristics. RESULTS: The F1 young spikes
      of winter wheat cross combination Yanfu188/Jimai37 were irradiated with gamma
      rays at a dose of 1.5 Gy to develop a new germplasm H307 with high anther culture
      ability. The proportion of green plantlets per 100 anthers (GP/100A) of H307 was
      14.50% which was higher than other H2 lines (P < 0.05). Analysis over three
      successive years (2006-2008) revealed that the green plantlet regeneration
      ability of H307 remained high in all 3 years. Reciprocal crosses between H307 and
      Nongda3308 showed no significant differences in their values for calli per 100
      anthers (CA/100A), green plantlets per 100 calli (GP/100C) and GP/100A (P >
      0.05). Five main wheat varieties used in production, namely Yumai68, Yanzhan4110,
      Bainongaikang58, Zhoumai18 and Xinmai18, were selected to cross with the new
      H307. CA/100A, GP/100C and GP/100A were used to assess the anther culture ability
      of F1 hybrids, demonstrating that the anther culture ability of H307 was
      heritable. CONCLUSION: H307 possessed high anther culture ability that was
      heritable, which would be potential germplasm for improving wheat anther breeding
      ability.

PMID- 24728941
TI  - Evolution of bacterial protein-tyrosine kinases and their relaxed specificity
      toward substrates.
AB  - It has often been speculated that bacterial protein-tyrosine kinases (BY-kinases)
      evolve rapidly and maintain relaxed substrate specificity to quickly adopt new
      substrates when evolutionary pressure in that direction arises. Here, we report a
      phylogenomic and biochemical analysis of BY-kinases, and their relationship to
      substrates aimed to validate this hypothesis. Our results suggest that BY-kinases
      are ubiquitously distributed in bacterial phyla and underwent a complex
      evolutionary history, affected considerably by gene duplications and horizontal
      gene transfer events. This is consistent with the fact that the BY-kinase
      sequences represent a high level of substitution saturation and have a higher
      evolutionary rate compared with other bacterial genes. On the basis of similarity
      networks, we could classify BY kinases into three main groups with 14 subgroups.
      Extensive sequence conservation was observed only around the three canonical
      Walker motifs, whereas unique signatures proposed the functional speciation and
      diversification within some subgroups. The relationship between BY-kinases and
      their substrates was analyzed using a ubiquitous substrate (Ugd) and some
      Firmicute-specific substrates (YvyG and YjoA) from Bacillus subtilis. No evidence
      of coevolution between kinases and substrates at the sequence level was found.
      Seven BY-kinases, including well-characterized and previously uncharacterized
      ones, were used for experimental studies. Most of the tested kinases were able to
      phosphorylate substrates from B. subtilis (Ugd, YvyG, and YjoA), despite
      originating from very distant bacteria. Our results are consistent with the
      hypothesis that BY-kinases have evolved relaxed substrate specificity and are
      probably maintained as rapidly evolving platforms for adopting new substrates.

PMID- 24728943
TI  - Divergent ecological strategies determine different impacts on community
      production by two successful non-native seaweeds.
AB  - The consequences of plant introductions into ecosystems are frequently reported
      from terrestrial environments, but little is known about the effects on ecosystem
      functioning caused by non-native primary producers in marine systems. In this
      study we explored the effects of the invasion by the two filamentous red algae
      Heterosiphonia japonica and Bonnemaisonia hamifera on the primary production of
      seaweed communities by using single and mixed cultures of non-native and native
      red algae. The experiments were conducted both in the presence and absence of
      herbivores. Biomass production of the invaded community increased more than four
      times in mixed cultures with H. japonica, while introduction by B. hamifera had
      no significant effect. The different impact on community production could be
      explained by differences in life history strategies between the invaders; H.
      japonica grew considerably faster than the native seaweeds which directly
      increased the community production, while B. hamifera showed a relatively slow
      growth rate and therefore had no effect. From previous studies it is known that
      B. hamifera produces a highly deterrent, but also costly, chemical defence. The
      assessment of survival and growth of a native generalist herbivore further
      corroborated that the biomass produced by B. hamifera constitutes a very low
      quality food, whereas the performance of herbivores on a diet of H. japonica was
      comparable to that on native algal diets. In summary, this study demonstrates
      that successful invaders belonging to the same functional group (filamentous red
      algae) may have distinctly different impacts on productivity in the recipient
      community, depending on their specific life history traits. 

PMID- 24728945
TI  - Retraction. Effects of osteopontin on expression of IL-6 and IL-8 inflammatory
      factors in human knee osteoarthritis chondrocytes.

PMID- 24728944
TI  - A long-term follow-up and comprehensive observation of risk and prognosis factors
      of recurrence and survival after resection of hepatocellular carcinoma.
AB  - Although HBV, liver function and tumor characteristics were proven as
      hepatocellular carcinoma (HCC) prognosis-related, no large-scale and long-term
      follow-up studies have ever given robust evidence about prognosis predictive
      effect and contribution to different stage of postoperation. In this study, we
      evaluated the influence of above index on overall survival (OS) and disease-free
      survival (DFS) and other clinical data in a rather large population and long-term
      follow-up. Our study consisted of 1,326 HCC patients who underwent radical
      resection from 1996 to 2010. Epidemiology, clinical and prognosis data were
      analyzed. Risk factors of OS and DFS were explored. Cumulative survival
      comparison between groups was performed with log-rank. Multivariate analysis for
      independent prognostic factors was determined by Cox proportional hazards model.
      HBsAg status was a universal factor of HCC recurrence, while preoperational
      albumin (ALB) and portal vein tumor thrombus (PVTT) affected survival during the
      whole lifetime. Early stage recurrence was associated with capsule intact [OR (95
      %) = 1.54,1.12-2.12, p = 0.009], preoperational alpha-fetoprotein (AFP), TNM and
      BCLC stages were the most important prognosis factors of recurrence in the early
      5 years and PVTT affected the rest time. Survival was mainly associated with
      tumor characteristic and ALB. Short-time survival was affected with age and AFP,
      while BCLC was related with the long-time survival. We confirmed that during
      different periods after resection, factors affecting prognosis did not remain
      unchanged. Liver function and tumor characteristic affected DFS and OS the whole
      time, especially the early recurrence. However, HBV infection situation was
      associated with later recurrence. PVTT showed an opposite effect between early
      and later recurrence.

PMID- 24728946
TI  - Achyranthes bidentata saponins promote osteogenic differentiation of bone marrow
      stromal cells through the ERK MAPK signaling pathway.
AB  - Achyranthes bidentata, is a herbal plant commonly used in the treatment of
      osteoporosis and bone nonunion in the Traditional Chinese Medicine. Saponins are
      the major compounds extracted from Achyranthes bidentata that have been shown to
      exert various pharmacological activities such as anti-inflammatory, antipyretic,
      antirheumatic, diuretic, and anti-osteoporosis. The Achyranthes bidentata
      saponins (ABS) were found to induce proliferation and differentiation in bone
      marrow stromal cells (BMSCs) as determined by the cell proliferation and alkaline
      phosphatase assays. Also, following the osteogenic induction, cells treated with
      ABS showed increased mRNA levels of rat bone morphogenetic protein-2, runt
      related transcription factor 2, and osterix. Furthermore, ABS stimulated the
      activation of ERK as evidenced by increased phosphorylation of these proteins,
      which was blocked by an inhibitor of ERK (PD98059). Taken together, these results
      suggest that ABS stimulated osteogenic differentiation of BMSCs via activation of
      the ERK signaling pathway.

PMID- 24728947
TI  - Detection of urine C2C and trace element level in patients with knee
      osteoarthritis.
AB  - The objective is to determine the relation between severity of knee
      osteoarthritis (KOA) and levels of Collagen type II metabolite (C2C) and trace
      elements in the urine. The urine sample and knee joint films (anteroposterior and
      lateral) from the KOA patients and control subjects were collected. The KOA
      patients were divided into five groups (controls and grades I-IV) according to
      the Kellgren-Lawrence radiographic grading standards. Urine levels of C2C and
      trace elements were detected by enzyme-linked immunosorbent assay and inductively
      coupled plasma atomic emission spectrometry, respectively. Urine C2C levels in
      the KOA subjects (261.235 +/- 39.944 pg/ml) were higher than those of the control
      group (218.341 +/- 22.270 pg/ml). The Fe content in KOA groups was significantly
      lower than that of control group (group IV > group III > group II > group I or
      controls). The contents of Cu and Zn were also significantly higher in the KOA
      patients than in the control group (p < 0.05). However, Cr, Al, Cd, Ni, and Se
      levels of KOA patients were not significantly different from those of the
      controls (p > 0.05). Determination of the urine levels of C2C and trace elements
      may prove to be informative for an early diagnosis of KOA. It can also assist in
      the prognosis judgment of the disease and selecting an appropriate therapeutic
      regimen.

PMID- 24728948
TI  - Ultrasound-microbubble transplantation of bone marrow stromal cells improves
      neurological function after forebrain ischemia in adult mice.
AB  - In this study, bone marrow stromal cells (MSCs) were transplanted into the brain
      of adult rats after forebrain ischemia induced by 4VO. SD rats (n = 60) were
      randomly divided into three groups: (I) rats (n = 20) were subjected to 4VO and
      transplanted with MSCs into the ischemic region using ultrasound-microbubble
      method, (2) rats (n = 20) were subjected to 4VO and transplanted with MSCs into
      the ischemic region (n = 20), and (3) 4VO alone (n = 20). Rats were sacrificed 28
      days after treatment. Neurological functions of rats were evaluated by Morris
      Water Maze. The current findings suggest that the ultrasound microbubble
      transplanted MSCs survived in the ischemic brain and significantly improved
      functional recovery of adult rats compared to regular transplantation.

PMID- 24728950
TI  - Impact of an alcohol-based hand sanitizer intervention on the spread of viruses
      in homes.
AB  - The objectives of this study were to determine the movement of a virus throughout
      a household and the impact of an alcohol-based hand sanitizer (ABHS) on reducing
      the movement and exposure of the virus to household members. Bacterial virus MS-2
      was used as the surrogate for human enteric and respiratory viruses. Seven
      households with families having at least two children in the age range of 2-18
      living in the home were used in this study. The hands of one adult family member
      were contaminated with 1 * 10(8). MS-2 bacteriophage in each home. After 8 h, the
      hands of each family member (10 fingers) and 20 frequently touched fomites were
      sampled to determine baseline contamination without intervention. Within 8 h, MS
      2 was detected on all of the family member's hands and most of the fomites. The
      intervention consisted of providing the families in all selected homes with
      bottles of an ABHS, which were placed in the kitchen, bathrooms, and nurseries.
      Smaller individual bottles were provided for each family member greater than 12
      years old to place in purses, pockets, backpacks, etc. The families were
      instructed to use the ABHS one time or three times during the day. For one and
      three uses, a statistically significant reduction of virus on un-inoculated and
      inoculated hands of ~99% occurred within 8 h. Similar reductions occurred on
      fomites throughout the households (97-99%). These results demonstrate that the
      use of an ABHS can significantly reduce transfer of a virus to the hands, and to
      the commonly touched surfaces within the household.

PMID- 24728949
TI  - Molecular characterization, expression pattern, and ligand-binding property of
      three odorant binding protein genes from Dendrolimus tabulaeformis.
AB  - Odorant binding proteins (OBPs) play important roles in insect olfactory
      processes. The Chinese pine caterpillar moth, Dendrolimus tabulaeformis
      (Lepidoptera, Lasiocampidae) is a serious economic pest in China, and the
      pheromones of this species have been identified to monitor their presence.
      However, the molecular mechanisms by which D. tabulaeformis perceive pheromones
      and host volatiles remain unknown. In this study, we identified and characterized
      three new OBPs, including one pheromone binding protein (PBP1) and two general
      odor binding proteins (GOBPs), from antennal cDNA of D. tabulaeformis. The
      deduced amino acid sequences of DtabPBP1, DtabGOBP1, and DtabGOBP2 revealed
      mature proteins of 140, 147, and 140 amino acids, respectively. Each has six
      cysteine residues in conserved positions relative to other known OBPs. Amino-acid
      alignments indicated that the two GOBPs are more conserved (DtabGOBP1 is 52.9
      67.4 % identical to orthologs from other Lepidoptera, and DtabGOBP2 is 55.2-81.8
      % identical) than the PBP (32.5-46.0 %). Real-time PCR indicated tissue- and sex
      specific expression patterns of the three genes. DtabPBP1 was mainly expressed in
      the antennae of males, whereas female antennae had only 1.09 % the expression in
      male antennae. Both DtabGOBP1 and DtabGOBP2 were more highly expressed in
      antennae than in other tissues, while DtabGOBP1 was more abundant in male
      antennae and DtabGOBP2 in female antennae. In addition, the binding specificities
      of the three proteins were investigated, and all three OBPs exhibited high
      binding affinities for the pheromone component (5Z,7E)-5,7-dodecadien-1-yl
      propionate (Z5,E7-12:OPr). This suggests a role in binding pheromone for GOBPs,
      as well as PBP1, in D. tabulaeformis. 

PMID- 24728952
TI  - An archived serum sample as a clue for identifying the primary source of a
      nosocomial hepatitis C virus outbreak in a haemodialysis unit.
AB  - Due to an unexpected technical error, patients at a dialysis unit who were
      seronegative for hepatitis C virus (HCV) were temporarily transferred to another
      dialysis unit next to a ward reserved for HCV-seropositive patients. In the
      following 7 months, 17 patients were diagnosed as anti-HCV positive. The aim of
      the study was to reveal the cause of this nosocomial infection. Anti-HCV-positive
      sera were further tested by molecular methods. Data collection and on-site
      epidemiologic inspections were carried out. The source of the nosocomial
      infection proved to be a seropositive patient treated at the unit, who died
      before the outbreak was recognized. The exact date of the infection was
      determined. 

PMID- 24728953
TI  - Berberine and monacolin effects on the cardiovascular risk profile of women with
      oestroprogestin-induced hypercholesterolemia.
AB  - INTRODUCTION: One of the most frequent side effect of oral contraceptives use is
      a stable alteration of the lipid profile. This could be even more relevant in
      women affected by polycystic ovary syndrome (PCOS). AIM: Considering the
      importance of a balanced lipid profile in cardiovascular prevention and that the
      exposure to the drugs could be many years long, our aim was to investigate the
      possible beneficial effect of a largely tested low-dosed combined lipid-lowering
      nutraceutical on dyslipidemias induced by oestroprogestins prescribed to young
      women for different indications. METHODS: We prospectively enrolled 84 patients
      in primary cardiovascular disease prevention, with low estimated cardiovascular
      disease risk (<5 % according to the ESC/EAS guidelines), and LDL-C increased
      above normal value (LDL-C >130 mg/dL) after the use of at least two different
      oral oestroprogestins treatments. Forty-four women were prescribed oral
      oestroprogestins for PCOS, while 40 for pure contraception. The tested
      nutraceutical contained berberine 500 mg/tab and monacolins 3 mg/tab was
      prescribed to all enrolled patients, associated the previously prescribed
      standard lipid-lowering diet. RESULTS: After 3 months of nutraceutical treatment,
      we observed a significant improvement in BMI (-1.5 +/- 0.8 %, p < 0.001), FPG (
      6.9 +/- 5.8 %, p < 0.001), HOMA index (-3.5 +/- 5.6 %, p < 0.001), TC (-20.1 +/-
      6.6 %, p < 0.001), LDL-C (-25.3 +/- 8.9 %, p < 0.001), HDL-C (+14.1 +/- 2.2 %, p
      < 0.001), TG (-29.9 +/- 25.2 %, p < 0.001) and hsCRP (-2.5 +/- 2.4 %, p = 0.019).
      Similar results have been obtained even repeating the analysis by subgroups,
      beyond hsCRP that significantly improved in PCOS patients compared to both the
      baseline and the non-PCOS group. CONCLUSION: It appears that the tested combined
      lipid-lowering nutraceutical is able to equally improve lipid metabolism in oral
      contraceptive induced hypercholesterolemia in women affected or not by PCOS.

PMID- 24728954
TI  - Resident physicians' clinical training and error rate: the roles of autonomy,
      consultation, and familiarity with the literature.
AB  - Resident physicians' clinical training poses unique challenges for the delivery
      of safe patient care. Residents face special risks of involvement in medical
      errors since they have tremendous responsibility for patient care, yet they are
      novice practitioners in the process of learning and mastering their profession.
      The present study explores the relationships between residents' error rates and
      three clinical training methods (1) progressive independence or level of
      autonomy, (2) consulting the physician on call, and (3) familiarity with up-to
      date medical literature, and whether these relationships vary among the
      specialties of surgery and internal medicine and between novice and experienced
      residents. 142 Residents in 22 medical departments from two hospitals
      participated in the study. Results of hierarchical linear model analysis
      indicated that lower levels of autonomy, higher levels of consultation with the
      physician on call, and higher levels of familiarity with up-to-date medical
      literature were associated with lower levels of resident's error rates. The
      associations varied between internal and surgery specializations and novice and
      experienced residents. In conclusion, the study results suggested that the
      implicit curriculum that residents should be afforded autonomy and progressive
      independence with nominal supervision in accordance with their relevant skills
      and experience must be applied cautiously depending on specialization and
      experience. In addition, it is necessary to create a supportive and judgment free
      climate within the department that may reduce a resident's hesitation to consult
      the attending physician. 

PMID- 24728956
TI  - The cerebral palsy transition clinic: administrative chore, clinical
      responsibility, or opportunity for audit and clinical research?
AB  - PURPOSE: The majority of children with orthopaedic conditions in childhood
      survive to adult life, and there is a need for many of them to transition to
      adult services. This includes children with disorders such as club foot or
      developmental dislocation of the hip as well as those with complex syndromic
      conditions, bone dysplasias or neuromuscular disorders such as cerebral palsy and
      myelomeningocele. In many tertiary paediatric centres, transition has become a
      formal process in which clinicians document and communicate the status of
      patients who have been under their care to ensure a smooth transfer to adult
      services. The purpose of this report is to support the need for clear
      communication when children with cerebral palsy transition to adult services and
      to suggest that this transition represents a significant opportunity for audit
      and clinical research. METHODS: Some of the factors to be considered in
      developing a minimum data sheet for the transfer or transition of children with
      cerebral palsy to adult services are described. CONCLUSION: Using the model of
      adolescents with cerebral palsy transitioning to adult services, orthopaedic
      surgeons can be encouraged to develop similar methodology and documentation for
      many other conditions for the purposes of communication, facilitation of
      transition, audit and clinical research.

PMID- 24728957
TI  - Targeted mutagenesis using CRISPR/Cas system in medaka.
AB  - Clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR
      associated (Cas) system-based RNA-guided endonuclease (RGEN) has recently emerged
      as a simple and efficient tool for targeted genome editing. In this study, we
      showed successful targeted mutagenesis using RGENs in medaka, Oryzias latipes.
      Somatic and heritable mutations were induced with high efficiency at the targeted
      genomic sequence on the DJ-1 gene in embryos that had been injected with the
      single guide RNA (sgRNA) transcribed by a T7 promoter and capped RNA encoding a
      Cas9 nuclease. The sgRNAs that were designed for the target genomic sequences
      without the 5' end of GG required by the T7 promoter induced the targeted
      mutations. This suggests that the RGEN can target any sequence adjacent to an NGG
      protospacer adjacent motif (PAM) sequence, which occurs once every 8 bp. The off
      target alterations at 2 genomic loci harboring double mismatches in the 18-bp
      targeting sequences were induced in the RGEN-injected embryos. However, we also
      found that the off-target effects could be reduced by lower dosages of sgRNA.
      Taken together, our results suggest that CRISPR/Cas-mediated RGENs may be an
      efficient and flexible tool for genome editing in medaka. 

PMID- 24728958
TI  - Colchicine-induced degeneration of the micronucleus during conjugation in
      Tetrahymena.
AB  - One of the most dramatic examples of nuclear morphogenesis occurs during
      conjugation in Tetrahymena when the micronucleus elongates to a size longer than
      the cell itself. After contraction to a spherical shape, the nucleus moves
      directly to chromosome separation in the first meiotic division. Here we
      investigate the consequences of interrupting the elongation process. Colchicine,
      a microtubule inhibitor, caused retraction of elongated structures. With time,
      cells began to lose their micronuclei, and by five hours more than half of the
      paired cells had at least one cell missing a micronucleus. After reversing the
      colchicine block, existing micronuclei did not undergo elongation again, nor did
      meiosis occur. These observations indicate that micronuclear elongation is
      critical to subsequent meiotic division. Further, nuclear elimination occurs,
      which could be due to meiotic failure or possibly a problem downstream from
      meiosis. An analysis of the process of colchicine-induced micronuclear
      degeneration indicated that it was regulated by a caspase-dependent mechanism,
      characteristic of apoptosis, and then resorbed by a lysosome-dependent autophagic
      mechanism. Amicronucleate cells failed to grow when returned to nutrient medium,
      likely because of a lesion in the post-conjugation reconstruction of a
      functioning oral apparatus. The ease by which a large number of nuclei are
      induced to "self-destruct" may make this system useful in investigating the link
      between colchicine treatment and nuclear death in Tetrahymena, and in
      investigating how nuclear death could be regulated in living cells more
      generally. Finally, we note that this phenomenon might relate to the evolution of
      amicronucleate species of Tetrahymena. 

PMID- 24728959
TI  - Hmga1/Hmga2 double knock-out mice display a "superpygmy" phenotype.
AB  - The HMGA1 and HMGA2 genes code for proteins belonging to the High Mobility Group
      A family. Several genes are negatively or positively regulated by both these
      proteins, but a number of genes are specifically regulated by only one of them.
      Indeed, knock-out of the Hmga1 and Hmga2 genes leads to different phenotypes:
      cardiac hypertrophy and type 2 diabetes in the former case, and a large reduction
      in body size and amount of fat tissue in the latter case. Therefore, to better
      elucidate the functions of the Hmga genes, we crossed Hmga1-null mice with mice
      null for Hmga2. The Hmga1(-/-)/Hmga2(-/-) mice showed reduced vitality and a very
      small size (75% smaller than the wild-type mice); they were even smaller than
      pygmy Hmga2-null mice. The drastic reduction in E2F1 activity, and consequently
      in the expression of the E2F-dependent genes involved in cell cycle regulation,
      likely accounts for some phenotypic features of the Hmga1(-/-)/Hmga2(-/-) mice. 

PMID- 24728960
TI  - The potential for macitentan, a new dual endothelin receptor antagonist, in the
      treatment of pulmonary arterial hypertension.
AB  - In recent years in the management of pulmonary arterial hypertension (PAH),
      endothelin receptor antagonists (ERAs) represent a well-established class of
      therapeutic agents with clear beneficial effects. Macitentan (Opsumit(r)), a dual
      ERA optimized for efficacy and safety, is the newest drug in the class.
      Macitentan presents a number of key beneficial characteristics, including
      increased in vivo preclinical efficacy versus existing ERAs, resulting from
      sustained receptor binding and physicochemical properties that allow enhanced
      tissue penetration. The clinical pharmacokinetics studies also indicated a low
      predilection of macitentan for drug-drug interactions. In the SERAPHIN trial, a
      phase III long-term study of PAH, macitentan significantly reduced morbidity and
      mortality by 45% versus placebo, providing sustained long-term improvements in
      exercise capacity. No association was found between changes in exercise capacity
      and long-term clinical outcomes, but improved cardiopulmonary hemodynamics were
      recorded in macitentan-treated patients irrespective of baseline background PAH
      therapy or World Health Organization functional class. Based on these favorable
      data, the US Food and Drug Administration approved the 10 mg/day dose in late
      2013 and the same process has recently been concluded by the European Medicines
      Agency.

PMID- 24728961
TI  - Identification of novel biomass-degrading enzymes from genomic dark matter:
      Populating genomic sequence space with functional annotation.
AB  - Although recent nucleotide sequencing technologies have significantly enhanced
      our understanding of microbial genomes, the function of ~35% of genes identified
      in a genome currently remains unknown. To improve the understanding of microbial
      genomes and consequently of microbial processes it will be crucial to assign a
      function to this "genomic dark matter." Due to the urgent need for additional
      carbohydrate-active enzymes for improved production of transportation fuels from
      lignocellulosic biomass, we screened the genomes of more than 5,500
      microorganisms for hypothetical proteins that are located in the proximity of
      already known cellulases. We identified, synthesized and expressed a total of 17
      putative cellulase genes with insufficient sequence similarity to currently known
      cellulases to be identified as such using traditional sequence annotation
      techniques that rely on significant sequence similarity. The recombinant proteins
      of the newly identified putative cellulases were subjected to enzymatic activity
      assays to verify their hydrolytic activity towards cellulose and lignocellulosic
      biomass. Eleven (65%) of the tested enzymes had significant activity towards at
      least one of the substrates. This high success rate highlights that a gene
      context-based approach can be used to assign function to genes that are otherwise
      categorized as "genomic dark matter" and to identify biomass-degrading enzymes
      that have little sequence similarity to already known cellulases. The ability to
      assign function to genes that have no related sequence representatives with
      functional annotation will be important to enhance our understanding of microbial
      processes and to identify microbial proteins for a wide range of applications.

PMID- 24728962
TI  - Respiratory nursing interventions following tracheostomy in acute traumatic
      cervical spinal cord injury.
AB  - Tracheostomy is frequently performed in severe cervical spinal cord injury (SCI)
      patients with the pulmonary dysfunction. A series of respiratory nursing
      interventions are required to plan tracheostomy removal. Tracheostomy was
      performed in 29 patients after acute traumatic cervical SCI. A series of
      respiratory nursing interventions were introduced in these patients after closed
      tracheostomy and decannulation, including closed tracheostomy tube training,
      manually assisted cough. Chacheostomy was successfully removed in 21 patients
      after the respiratory nursing interventions. In contrast, eight patients died
      from associated injuries. The average time from tracheostomy to decannulation was
      40 days (14-104 days), the average time from closed tracheostomy to decannulation
      was 18.80 +/- 13.50 days. Second tracheostomy was performed in one patient after
      29 days' removal due to pulmonary infection. One patient presented with delayed
      incision healing for 29 days. Closed tracheostomy tube training and manually
      assisted cough are key factors for tracheostomy removal, although intensive
      nursing are also needed. The time from tracheostomy to decannulation and from
      closed tracheostomy to decannulation is increased in case of "late" (>24 h)
      tracheostomy and longer mechanical ventilation.

PMID- 24728963
TI  - An anatomic study of the structure and innervation of the pronator quadratus
      muscle.
AB  - The pronator quadratus muscle is composed of the superficial and deep heads.
      However, to date there is no consensus on the variations of each head. To add to
      this enigma, the innervation patterns of each head have not been thoroughly
      studied. The present study was conducted to clarify the structure and innervation
      of the pronator quadratus muscle by minute dissection of 46 forearms from 26
      cadavers. The origin, insertion, shape, and direction of the muscle fascicles in
      each head were observed. The intramuscular distribution and the innervation
      patterns to each head were investigated. The attachment of the deep head was
      examined using Masson's trichrome staining technique. Each head consisted of
      various muscle fascicles which differed in shape and direction. The most distal
      muscle fascicle extended toward the head of the ulna. On microscopic study, this
      most distal fascicle was observed to reach the base of the ulnar styloid process.
      The nerves innervating the superficial head penetrated through the deep head and
      ran on the anterior surface of the radius from medial to lateral. This tendency
      was common to all of the forearms studied. We confirmed that each head of the
      pronator quadratus muscle consisted of various muscle fascicles. The attachment
      to the base of the ulnar styloid process is considered to be an important
      structure that prevents the head of the ulna from impacting against the carpal
      bones. Knowledge of the innervation pattern to each head is critical for
      preserving the function of the pronator quadratus muscle during surgery for
      distal radial fracture. 

PMID- 24728964
TI  - M13 bacteriophage production for large-scale applications.
AB  - Bacteriophage materials have the potential to revolutionize medicine, energy
      production and storage, agriculture, solar cells, optics and many other fields.
      To fulfill these needs, this study examined critical process parameters during
      phage propagation to increase phage production capability. A representative scale
      down system was created in tube spin reactors to allow parallel experimentation
      with single- and multi-variable analysis. Temperature, harvest time, media
      composition, feed regime, bacteriophage, and bacteria concentration were analyzed
      in the scale-down system. Temperature, media composition, and feeding regimens
      were found to affect phage production more than other factors. Temperature
      affected bacterial growth and phage production inversely. Multi-variate analysis
      identified an optimal parameter space which provided a significant improvement
      over the base line method. This method should be useful in scaled production of
      bacteriophage for biotechnology. 

PMID- 24728965
TI  - Investigation of continuous-batch mode of two-stage culture of Nannochloropsis
      sp. for lipid production.
AB  - Microalgal lipid induction through nitrogen stress often suffers from a
      contradiction between biomass productivity and lipid content, i.e., either high
      biomass productivity with low lipid content or vice versa. A two-stage nitrogen
      replete and nitrogen-deplete (NR-ND) culture was suggested to be an option to
      attain high lipid productivity. In this study, the effects of culture conditions
      and modes on biomass productivity and lipid productivity of Nannochloropsis sp.
      in the two stages were comprehensively investigated. The optimal culture
      conditions for the two stages, aiming to high biomass productivity and lipid
      productivity respectively, were consistent, i.e., CO2 content in aeration (1 %),
      phosphorus concentration in medium (181 MUmol/L), incident light intensity (150
      MUE/(m(2)s)), temperature (25  degrees C). Different culture modes of the two
      stages were compared. The overall lipid productivity of the two-stage continuous
      batch mode achieved 0.123 g/(L day), which was 60.3, 48.2, 34.9 and 13.5 % higher
      than that of single nitrogen-replete batch, single nitrogen-limited batch,
      continuous nitrogen-replete culture and two-stage batch-batch culture,
      respectively, and also higher than most reported values. This contribution
      provides fundamental data for the two-stage NR-ND cultivation process design of
      Nannochloropsis sp. 

PMID- 24728966
TI  - An ALTernate interpretation of serum transaminases.

PMID- 24728967
TI  - The role of phospholipase D1 in liver fibrosis induced by dimethylnitrosamine in
      vivo.
AB  - BACKGROUND: Phospholipase D (PLD) has been proved to be involved in regulating
      function of fibroblasts and might play a role in mediating organic fibrosis.
      AIMS: To investigate the role and mechanism of PLD on dimethylnitrosamine (DMN)
      induced rat liver fibrosis. METHODS: Fifty-five male Wistar rats were divided
      into normal control group, DMN model group, N-methylethanolamine (MEA) control
      group, and MEA-intervention group. We observed the effects of MEA, a PLD
      inhibitor on the development and progression of rat liver fibrosis by comparing
      the physical and biochemical indexes, tissue pathology, PLD activity, and typical
      markers and cytokines related to fibrosis in the four groups. RESULTS:
      Accompanied by the down-regulation of PLD1 expression, the MEA-intervention group
      had improved outcomes compared with the DMN model group in terms of spleen
      weight, spleen/weight index, serum and tissue biochemical indexes, tissue
      hydroxyproline, and tissue pathology. The MEA-intervention group had lower TIMP1,
      COL1A1, and higher MMPs expression level than the DMN model group. The activity
      of PLD and PLD1, alpha-SMA expression level in the MEA-intervention group was
      much lower than those in the DMN model group. There was no significant difference
      between the two groups in the expression level of TGF-beta1 and MCP1. Meanwhile,
      there were no significant differences between normal control group and MEA
      control group in the parameters stated above. CONCLUSION: Phospholipase D1 may
      play an important role in the development and progression of rat liver fibrosis.
      Inhibition of PLD may become a new strategy to prevent or alleviate liver
      fibrosis.

PMID- 24728968
TI  - Characteristics and management of patients with chronic hepatitis B in an
      integrated care setting.
AB  - BACKGROUND: Few population-based studies have described characteristics and
      management of patients with chronic hepatitis B (CHB) in the USA. METHODS: We
      retrospectively studied adults with CHB in the Northern California Kaiser
      Permanente Medical Care Program (KPNC) from July 2009 to December 2010 (n =
      12,016). Laboratory tests, treatment patterns, and hepatocellular carcinoma (HCC)
      surveillance were ascertained during a "recent" 18-month study window (July 2009
      December 2010), or as "ever" based on records dating to 1995. RESULTS: The mean
      age was 49 years; 51 % were men, 83 % Asian, and 87 % KPNC members >5 years.
      Overall, 51 % had >= 1 liver-related visit, 14 % with gastroenterology or
      infectious disease specialists, and 37 % with primary care providers (PCP) only.
      Less than 40 % of patients had both hepatitis B virus (HBV) DNA and ALT testing
      conducted recently, while 56 % of eligible patients had received HCC
      surveillance. Recent laboratory testing and HCC surveillance were more frequent
      in patients seen by a specialist versus PCP only (90 vs. 47 % and 92 vs. 73 %,
      respectively, p values <0.001). During the study period, 1,649 (14 %) received
      HBV treatment, while 5 % of untreated patients had evidence of treatment
      eligibility. Among 599 patients newly initiated on HBV therapy, 76 % had
      guideline-based indications for treatment. CONCLUSIONS: Most patients initiated
      on HBV treatment met eligibility, and very few patients with evidence of needing
      treatment were left untreated. However, monitoring of ALT and HBV DNA levels, as
      well as HCC surveillance, were not frequent, underestimating the proportion of
      patients that warranted HBV therapy. Viral monitoring and cancer surveillance are
      therefore important targets for improving the scope of CHB care in the community
      setting.

PMID- 24728971
TI  - Thermoregulatory correlates of nausea in rats and musk shrews.
AB  - Nausea is a prominent symptom and major cause of complaint for patients receiving
      anticancer chemo- or radiation therapy. The arsenal of anti-nausea drugs is
      limited, and their efficacy is questionable. Currently, the development of new
      compounds with anti-nausea activity is hampered by the lack of physiological
      correlates of nausea. Physiological correlates are needed because common
      laboratory rodents lack the vomiting reflex. Furthermore, nausea does not always
      lead to vomiting. Here, we report the results of studies conducted in four
      research centers to investigate whether nausea is associated with any specific
      thermoregulatory symptoms. Two species were studied: the laboratory rat, which
      has no vomiting reflex, and the house musk shrew (Suncus murinus), which does
      have a vomiting reflex. In rats, motion sickness was induced by rotating them in
      their individual cages in the horizontal plane (0.75 Hz, 40 min) and confirmed by
      reduced food consumption at the onset of dark (active) phase. In 100% of rats
      tested at three centers, post-rotational sickness was associated with marked
      (~1.5 degrees C) hypothermia, which was associated with a short-lasting tail-skin
      vasodilation (skin temperature increased by ~4 degrees C). Pretreatment with
      ondansetron, a serotonin 5-HT3 receptor antagonist, which is used to treat nausea
      in patients in chemo- or radiation therapy, attenuated hypothermia by ~30%. In
      shrews, motion sickness was induced by a cyclical back-and-forth motion (4 cm, 1
      Hz, 15 min) and confirmed by the presence of retching and vomiting. In this
      model, sickness was also accompanied by marked hypothermia (~2 degrees C). Like
      in rats, the hypothermic response was preceded by transient tail-skin
      vasodilation. In conclusion, motion sickness is accompanied by hypothermia that
      involves both autonomic and thermoeffector mechanisms: tail-skin vasodilation and
      possibly reduction of the interscapular brown adipose tissue activity. These
      thermoregulatory symptoms may serve as physiological correlates of nausea. 

PMID- 24728972
TI  - Soluble TNFalpha-receptor 1 as a predictor of coronary calcifications in patients
      after long-term cure of Cushing's syndrome.
AB  - PURPOSE: Increased cardiovascular (CV) risk persists in Cushing's syndrome (CS),
      despite remission of hypercortisolism. The aim of this study was to evaluate
      prevalence of coronary artery disease in CS patients and its correlation with
      classical CV risk factors and inflammatory markers. METHODS: Cardiac
      multidetector computed tomography (MDCT) was performed in 41 patients (7 men, 31
      of pituitary origin, 29 cured, mean age: 48.6 +/- 13 years), using 64-slice
      Toshiba Aquilion systems. Coronary atherosclerotic plaques were detected and
      coronary calcifications quantified by the Agatston score (AS). Clinical and
      biochemical parameters were correlated with the AS to identify possible surrogate
      markers of coronary disease. Normal values for clinical and biochemical
      parameters were obtained from a gender- and age-matched normal reference
      population (n = 82). RESULTS: CS patients with calcifications (AS > 0) (N = 13,
      32%) had higher levels of sTNF-R1, homocysteine, triglycerides, blood pressure
      and body mass index than patients without calcifications (AS = 0) and those of
      normal reference population. Both groups of CS patients (AS > 0 and AS = 0) had
      elevated trunk fat mass and IL-6 compared to reference values. Patients with AS >
      0 had less adiponectin and higher insulin, HOMA and fibrinogen than those found
      in normal reference population. sTNF-R1 correlated positively with AS and
      remained significant after adjusting for confounding factors. The same result was
      observed when we considered only cured CS patients. CONCLUSION: In our cohort of
      CS patients sTNF-R1 was a predictor of coronary calcifications. Since MDCT is an
      expensive technique not readily available in daily clinical practice, increased
      sTNF-R1 could be a marker of CV risk even in cured CS.

PMID- 24728974
TI  - Discriminating multiplexed GFP reporters in primary articular chondrocyte
      cultures using image cytometry.
AB  - Flow cytometry has become a standard tool for defining a heterogeneous cell
      population based on surface expressed epitopes or GFP reporters that reflect cell
      types or cellular differentiation. The introduction of image cytometry raised the
      possibility of adaptation to discriminate GFP reporters used to appreciate cell
      heterogeneity within the skeletal lineages. The optical filters and LEDs were
      optimized for the reporters used in transgenic mice expressing various
      fluorescent proteins. In addition, the need for compensation between eGFP and
      surrounding reporters due to optical cross-talk was eliminated by selecting the
      appropriate excitation and emission filters. Bone marrow or articular cartilage
      cell cultures from GFP and RFP reporter mouse lines were established to
      demonstrate the equivalency in functionalities of image to flow cytometry
      analysis. To examine the ability for monitoring primary cell differentiation,
      articular chondrocyte cell cultures were established from mice that were single
      or doubly transgenic (Dkk3eGFP and Col2A1GFPcyan), which identify the progression
      of superficial small articular cell to a mature chondrocyte. The instrument was
      able to rapidly and accurately discriminate cells that were Dkk3eGFP only,
      Dkk3eGFP/Col2A1GFPcyan, and Col2A1GFP, which provides a useful tool for studying
      the impact of culture conditions on lineage expansion and differentiation. 

PMID- 24728976
TI  - Neck hematoma complicating endotracheal extubation.

PMID- 24728975
TI  - Posterior spinal fusion to sacrum in non-ambulatory hypotonic neuromuscular
      patients: sacral rod/bone graft onlay method.
AB  - PURPOSE: A retrospective study involving 65 non-ambulatory patients with
      hypotonic neuromuscular scoliosis has assessed the effectiveness of a sacral
      rod/bone onlay technique for extending spinal fusion to the sacrum. METHODS: To
      extend posterior spinal fusion to the sacrum, we used either 1 Harrington rod and
      1 Luque L rod with sublaminar wires in 14 patients (Group 1) or two rods with
      sublaminar wires in 51 patients (Group 2) along with abundant autograft and
      allograft bone covering the ends of the rods. RESULTS: Diagnoses were Duchenne
      muscular dystrophy 53, spinal muscular atrophy 4, myopathy 3, limb girdle
      muscular dystrophy 2, infantile FSH muscular dystrophy 1, cerebral palsy 1, and
      Friedreich ataxia 1. Mean age at surgery was 14.3 years (+/-2.2, range 10.9
      25.2). Radiographic follow-up (2 years post-surgery or greater) was 6.4 years (+/
      4.4, range 2-25.3). Using the onlay technique, all patients fused with no rod
      breakage or pseudarthrosis. For the entire series, the mean pre-operative
      scoliosis was 54.7 degrees  (+/-31.1, range 0 degrees -120 degrees ) with post
      operative correction to 21.8 degrees  (+/-21.7, range 0 degrees -91 degrees ) and
      long-term follow-up 24 degrees  (+/-22.9, range 0 degrees -94 degrees ). For
      pelvic obliquity, pre-operative deformity was 17.3 degrees  (+/-11.3, range 0
      degrees -51 degrees ) with post-operative correction to 8.9 degrees  (+/-7.8,
      range 0 degrees -35 degrees ) and long-term follow-up 10.1 degrees  (+/-8.1,
      range 0 degrees -27 degrees ). Five required revision at a mean of 3.3 years post
      original surgery involving rod shortening at the distal end. One of these had
      associated infection. CONCLUSION: Lumbosacral stability and long-term sitting
      comfort have been achieved in all patients. Problems can be minimized by
      positioning the rods firmly against the sacrum at the time of surgery with a
      relatively short extension beyond the L5-S1 junction. The procedure is valuable
      in hypotonic non-ambulatory neuromuscular patients whose immobility enhances the
      success rate for fusion due to diminished stress at the lumbosacral junction. It
      is particularly warranted for those with osteoporosis and a small, deformed
      pelvis. Considerable weight loss and lengthy rods not closely apposed to the
      sacrum at the time of surgery played a major role in patients needing revision.

PMID- 24728977
TI  - A unique case of facial burn superinfected with Dermatobia Hominis larvae
      resulting in a bilateral enucleation of the eyes.
AB  - We present a case of a female Ecuadorian patient who presented a deep facial burn
      injury complicated with a severe infestation of Dermatobia Hominis larvae. The
      burn injury was complicated by severe myiasis attributable to the poor management
      of the wound received at home, using tropical plants, which caused a secondary
      infection and severe necrosis of the tissue involving the forehead, cheeks, chin,
      scalp, nose, mouth and the eyes resulting in a bilateral enucleation and long
      inpatient hospital care. 

PMID- 24728978
TI  - NEDD9 crucially regulates TGF-beta-triggered epithelial-mesenchymal transition
      and cell invasion in prostate cancer cells: involvement in cancer
      progressiveness.
AB  - BACKGROUND: NEDD9 is one of the Crk-associated substrate (Cas) family proteins
      that mediate downstream signaling processes including cytoskeletal organization,
      cell-cycle and tumorigenesis. While NEDD9 plays a crucial role in epithelial
      mesenchymal transition (EMT), the functional mechanism underlying NEDD9-mediated
      EMT in prostate cancer (PCa) remains uncertain. METHODS: The expression levels of
      NEDD9 and its downstream molecules in PC-3, LNCaP, and VCaP cells exposed to
      transforming growth factor-beta (TGF-beta) were determined by western blotting.
      The invasion of these cells with ectopic overexpression of NEDD9 or silencing of
      NEDD9 expression was measured by transwell invasion assay. Human tissue samples
      comprising 45 PCa specimens and ten specimens of normal prostatic tissue were
      used for immunohistochemical (IHC) analysis of NEDD9 expression. RESULTS: Both
      NEDD9 and its downstream signaling molecules associated with EMT were strongly
      induced by TGF-beta in PCa cells. PC-3 cells with stable overexpression of NEDD9
      had a mesenchymal phenotype and significantly enhanced cell invasion, despite
      their decreased cell proliferation. Knockdown of endogenous NEDD9 expression
      completely diminished TGF-beta-triggered tumor invasion in several PCa cell
      lines. The IHC data revealed a significant positive correlation between the NEDD9
      staining score and tumor aggressiveness (e.g., Gleason grade, serum PSA level).
      The NEDD9 staining score in primary PCa with bone metastasis was significantly
      higher than that in PCa without metastasis. CONCLUSIONS: NEDD9 may be a key
      mediator involved in TGF-beta-mediated EMT and cell motility in PCa cells and a
      novel target in the treatment of metastatic PCa and prevention of spread of
      localized PCa cells to other organs.

PMID- 24728979
TI  - Random survival forests for competing risks.
AB  - We introduce a new approach to competing risks using random forests. Our method
      is fully non-parametric and can be used for selecting event-specific variables
      and for estimating the cumulative incidence function. We show that the method is
      highly effective for both prediction and variable selection in high-dimensional
      problems and in settings such as HIV/AIDS that involve many competing risks. 

PMID- 24728980
TI  - Identification of manipulated variables for a glycosylation control strategy.
AB  - N-linked glycan distribution affects important end-use characteristics such as
      the bioactivity and efficacy of many therapeutic proteins, (including monoclonal
      antibodies), in vivo. Yet, obtaining desired glycan distributions consistently
      during batch-to-batch production can be challenging for biopharmaceutical
      manufacturers. While an appropriately implemented on-line glycosylation control
      strategy during production can help to ensure a consistent glycan distribution,
      to date no such strategies have been reported. Our goal is to develop and
      validate a comprehensive strategy for effective on-line control of glycosylation,
      the successful achievement of which requires first identifying appropriate
      manipulated variables that can be used to direct the glycan distribution to a
      desired state. While various culture conditions such as bioreactor process
      variables, media type, and media supplements have been shown to affect the glycan
      distribution, in this study we focus on the latter. Specifically, we implemented
      a statistically designed series of experiments to determine the significant main
      effects (as well as interaction effects) of media supplementation with manganese,
      galactose, ammonia and found that each had significant effects on certain
      glycans. We also include data indicating the glycosylation enzyme gene transcript
      levels as well as the intracellular nucleotide sugar concentrations in the
      presence of the media supplements to provide insight into the intracellular
      conditions that may be contributing to the changes in glycan distribution. The
      acquired experimental data sets were then used to identify which glycans can be
      controlled by the media supplements and to what degree. We determined that MnCl2
      can be used as a manipulated variable to increase the relative abundance of M51
      and decrease FA2 simultaneously, and galactose can be used as a manipulated
      variable to increase the relative abundance of FA2G1 and decrease FA2 and A2
      simultaneously.

PMID- 24728981
TI  - Dietary L-arginine modulates immunosuppression in broilers inoculated with an
      intermediate strain of infectious bursa disease virus.
AB  - BACKGROUND: The effects of dietary l-arginine (Arg) on immunosuppression
      following infectious bursal disease virus (IBDV) inoculation in broiler chickens
      were evaluated. The design of this study was a 5 * 2 factorial arrangement (n =
      5) with five Arg concentrations (starter: 9.9, 13.9, 17.6, 21.3 and 25.3 g kg(-1)
      ; grower-finisher: 9.5, 13.5, 17.1, 20.1 and 23.6 g kg(-1) ) with or without IBDV
      inoculation (IBDV or saline inoculation at 14 days). Chickens were sampled at 2,
      4 and 6 days post-inoculation (DPI) and 42 days of age. RESULTS: The IBDV
      inoculation decreased (P = 0.05) CD3(+) , CD4(+) , and CD8(+) T cell counts at 2
      days post-inoculation (DPI) and monocyte counts at 6 DPI; and reduced (P < 0.05)
      bursal interleukin-1beta (IL-1beta) mRNA expression at 2 DPI and serum IL-6
      concentration at 4 DPI. Increasing Arg concentration increased (P < 0.05) CD4(+)
      and CD8(+) T cell counts at 2 DPI, linearly increased (P = 0.05) CD3(+) T cell
      counts in IBDV-inoculated groups and monocyte counts in control groups at 4 DPI;
      increased (P < 0.05) serum IL-6 concentration in IBDV-inoculated groups at 2 DPI;
      and increased (P < 0.05) serum anti-IBDV antibody titres at 42 days of age.
      CONCLUSION: Varying concentrations of Arg supplementation attenuated IBDV
      inoculation induced immunosuppression via modulating circulating T cell sub
      populations.

PMID- 24728984
TI  - Impact of ambient and supplemental ultraviolet-B stress on kidney bean plants: an
      insight into oxidative stress management.
AB  - In the present study, the response of kidney bean (Phaseolus vulgaris L. cv. Pusa
      Komal) plants was evaluated under three different levels of ultraviolet-B (UV-B),
      i.e., excluded UV-B (eUV-B), ambient UV-B (aUV-B; 5.8 kJ m(-2) day(-1)), and
      supplemental UV-B (sUV-B; 280-315 nm; ambient + 7.2 kJ m(-2) day(-1)), under near
      natural conditions. eUV-B treatment clearly demonstrated that both aUV-B and sUV
      B are capable of causing significant changes in the plant's growth, metabolism,
      economic yield, genome template stability, total protein, and antioxidative
      enzyme profiles. The experimental findings showed maximum plant height at eUV-B,
      but biomass accumulation was minimum. Significant reductions in quantum yield
      (Fv/Fm) were observed under both aUV-B and sUV-B, as compared to eUV-B. UV-B
      absorbing flavonoids increased under higher UV-B exposures with consequent
      increments in phenylalanine ammonia lyase (PAL) activities. The final yield was
      significantly higher in plants grown under eUV-B, compared to those under aUV-B
      and sUV-B. Total protein profile through sodium dodecyl sulfate-polyacrylamide
      gel electrophoresis (SDS-PAGE) and analysis of isoenzymes, like superoxide
      dismutase (SOD), peroxidase (POX), catalase (CAT), ascorbate peroxidase (APX),
      guaiacol peroxidase (GPX), and glutathione reductase (GR), through native PAGE
      revealed major changes in the leaf proteome under aUV-B and sUV-B, depicting
      induction of some major stress-related proteins. The random amplified polymorphic
      DNA (RAPD) profile of genomic DNA also indicated a significant reduction of
      genome template stability under UV-B exposure. Thus, it can be inferred that more
      energy is diverted for inducing protection mechanisms rather than utilizing it
      for growth under high UV-B level.

PMID- 24728985
TI  - Pancreatic hyperenzymemia is associated with bacterial culture positivity, more
      severe and right-sided colitis.
AB  - BACKGROUND/AIM: Several studies reported pancreatic hyperenzymemia (PHE) related
      to acute colitis. However, there is no consensus on its clinical significance.
      This study was addressed to find the clinical significance of PHE in acute
      colitis. METHODS: Pancreatic hyperenzymemia was defined as abnormal increase in
      serum concentrations of the pancreatic enzymes by three times of normal upper
      range without definite pancreatic symptoms and evidence of pancreatitis at
      abdominal CT imaging of pancreatic disease. And clinical and laboratory and
      biologic parameters of PHE group and normal pancreatic enzymemia (NPE) group were
      compared. RESULTS: A total of 1,069 patients admitted to hospitals due to acute
      colitis were analyzed. Of these patients, 2.99 % (32/1,069) showed PHE. PHE group
      showed more severe symptoms and had longer hospital stays than the NPE group
      (12.15 vs. 4.59 days; P < 0.001). Multivariable analysis showed that right-sided
      colitis (OR 2.846; 95 % CI 1.122-7.224; P = 0.028) and culture positivity (OR
      3.346; 95 % CI 1.119-10.008; P = 0.031) are associated with PHE during acute
      colitis. Also, PHE group was more common when a microorganism could be identified
      in the cultures (28.1 vs. 7.0 %; P = 0.003), especially blood culture. Among
      patients with positive cultures, Salmonella spp. had a positive correlation with
      the right-sided colitis and PHE (amylase P = 0.002; lipase P = 0.029), Salmonella
      serovar typhimurium (group B) was especially related to increased serum lipase
      but not to increased serum amylase (lipase; P = 0.041: amylase; P = 0.485).
      CONCLUSION: Pancreatic hyperenzymemia is associated with right-sided colitis,
      bacterial culture positivity, and severe acute colitis.

PMID- 24728983
TI  - Modeling neurodevelopmental disorders using human pluripotent stem cells.
AB  - Neurodevelopmental disorders (NDs) are impairments that affect the development
      and growth of the brain and the central nervous system during embryonic and early
      postnatal life. Genetically manipulated animals have contributed greatly to the
      advancement of ND research, but many of them differ considerably from the human
      phenotype. Cellular in vitro models are also valuable, but the availability of
      human neuronal cells is limited and their lifespan in culture is short. Human
      pluripotent stem cells (hPSCs), including embryonic stem cells and induced
      pluripotent stem cells, comprise a powerful tool for studying developmentally
      regulated diseases, including NDs. We reviewed all recent studies in which hPSCs
      were used as in vitro models for diseases and syndromes characterized by
      impairment of neurogenesis or synaptogenesis leading to intellectual disability
      and delayed neurodevelopment. We analyzed their methodology and results, focusing
      on the data obtained following in vitro neural differentiation and gene
      expression and profiling of the derived neurons. Electrophysiological recording
      of action potentials, synaptic currents and response to neurotransmitters is
      pivotal for validation of the neuronal fate as well as for assessing phenotypic
      dysfunctions linked to the disease in question. We therefore focused on the
      studies which included electrophysiological recordings on the in vitro-derived
      neurons. Finally, we addressed specific issues that are critical for the
      advancement of this area of research, specifically in providing a reliable human
      pre-clinical research model and drug screening platform. 

PMID- 24728986
TI  - A novel mechanism for regulating the activity of proliferating cell nuclear
      antigen by a small protein.
AB  - Proliferating cell nuclear antigen (PCNA) forms a trimeric ring that associates
      with and influences the activity of many proteins participating in DNA metabolic
      processes and cell cycle progression. Previously, an uncharacterized small
      protein, encoded by TK0808 in the archaeon Thermococcus kodakarensis, was shown
      to stably interact with PCNA in vivo. Here, we show that this protein, designated
      Thermococcales inhibitor of PCNA (TIP), binds to PCNA in vitro and inhibits PCNA
      dependent activities likely by preventing PCNA trimerization. Using
      hydrogen/deuterium exchange mass spectrometry and site-directed mutagenesis, the
      interacting regions of PCNA and TIP were identified. Most proteins bind to PCNA
      via a PCNA-interacting peptide (PIP) motif that interacts with the inter domain
      connecting loop (IDCL) on PCNA. TIP, however, lacks any known PCNA-interacting
      motif, suggesting a new mechanism for PCNA binding and regulation of PCNA
      dependent activities, which may support the development of a new subclass of
      therapeutic biomolecules for inhibiting PCNA. 

PMID- 24728987
TI  - Rapid kinetics of iron responsive element (IRE) RNA/iron regulatory protein 1 and
      IRE-RNA/eIF4F complexes respond differently to metal ions.
AB  - Metal ion binding was previously shown to destabilize IRE-RNA/IRP1 equilibria and
      enhanced IRE-RNA/eIF4F equilibria. In order to understand the relative importance
      of kinetics and stability, we now report rapid rates of protein/RNA complex
      assembly and dissociation for two IRE-RNAs with IRP1, and quantitatively
      different metal ion response kinetics that coincide with the different iron
      responses in vivo. kon, for FRT IRE-RNA binding to IRP1 was eight times faster
      than ACO2 IRE-RNA. Mn(2+) decreased kon and increased koff for IRP1 binding to
      both FRT and ACO2 IRE-RNA, with a larger effect for FRT IRE-RNA. In order to
      further understand IRE-mRNA regulation in terms of kinetics and stability, eIF4F
      kinetics with FRT IRE-RNA were determined. kon for eIF4F binding to FRT IRE-RNA
      in the absence of metal ions was 5-times slower than the IRP1 binding to FRT IRE
      RNA. Mn(2+) increased the association rate for eIF4F binding to FRT IRE-RNA, so
      that at 50 uM Mn(2+) eIF4F bound more than 3-times faster than IRP1. IRP1/IRE-RNA
      complex has a much shorter life-time than the eIF4F/IRE-RNA complex, which
      suggests that both rate of assembly and stability of the complexes are important,
      and that allows this regulatory system to respond rapidly to change in cellular
      iron.

PMID- 24728988
TI  - Synthetic circuit for exact adaptation and fold-change detection.
AB  - Biological organisms use their sensory systems to detect changes in their
      environment. The ability of sensory systems to adapt to static inputs allows wide
      dynamic range as well as sensitivity to input changes including fold-change
      detection, a response that depends only on fold changes in input, and not on
      absolute changes. This input scale invariance underlies an important strategy for
      search that depends solely on the spatial profile of the input. Synthetic efforts
      to reproduce the architecture and response of cellular circuits provide an
      important step to foster understanding at the molecular level. We report the
      bottom-up assembly of biochemical systems that show exact adaptation and fold
      change detection. Using a malachite green aptamer as the output, a synthetic
      transcriptional circuit with the connectivity of an incoherent feed-forward loop
      motif exhibits pulse generation and exact adaptation. A simple mathematical model
      was used to assess the amplitude and duration of pulse response as well as the
      parameter regimes required for fold-change detection. Upon parameter tuning, this
      synthetic circuit exhibits fold-change detection for four successive rounds of
      two-fold input changes. The experimental realization of fold-change detection
      circuit highlights the programmability of transcriptional switches and the
      ability to obtain predictive dynamical systems in a cell-free environment for
      technological applications. 

PMID- 24728989
TI  - 5-Fluorouracil affects assembly of stress granules based on RNA incorporation.
AB  - The antimetabolite 5-fluorouracil is a widely used chemotherapeutic for the
      treatment of several solid cancers. However, resistance to 5-fluorouracil remains
      a major drawback in its clinical use. In this study we report that treatment of
      HeLa cells with 5-fluorouracil resulted in de novo assembly of stress granules.
      Moreover, we revealed that stress granule assembly under stress conditions as
      well as disassembly is altered in cells treated with 5-fluorouracil. Notably, we
      discovered that RACK1, a protein mediating cell survival and apoptosis, is a
      component of 5-fluorouracil-induced stress granules. To explore the mode of
      action of 5-fluorouracil accountable for de novo stress granule assembly, we
      analyzed 5-fluorouracil metabolites and noticed that stress granule assembly is
      caused by RNA, not DNA incorporating 5-fluorouracil metabolites. Interestingly,
      we observed that other RNA incorporating drugs also cause assembly of stress
      granules. Thus, our results suggest that incorporation of chemotherapeutics into
      RNA may result in stress granule assembly with potential significance in
      chemoresistance. 

PMID- 24728990
TI  - The E3 ubiquitin ligase UBE3A is an integral component of the molecular circadian
      clock through regulating the BMAL1 transcription factor.
AB  - Post-translational modifications (such as ubiquitination) of clock proteins are
      critical in maintaining the precision and robustness of the evolutionarily
      conserved circadian clock. Ubiquitination of the core clock transcription factor
      BMAL1 (brain and muscle Arnt-like 1) has recently been reported. However, it
      remains unknown whether BMAL1 ubiquitination affects circadian pacemaking and
      what ubiquitin ligase(s) is involved. Here, we show that activating UBE3A (by
      expressing viral oncogenes E6/E7) disrupts circadian oscillations in mouse
      embryonic fibroblasts, measured using PER2::Luc dynamics, and rhythms in
      endogenous messenger ribonucleic acid and protein levels of BMAL1. Over
      expression of E6/E7 reduced the level of BMAL1, increasing its ubiquitination and
      proteasomal degradation. UBE3A could bind to and degrade BMAL1 in a ubiquitin
      ligase-dependent manner. This occurred both in the presence and absence of E6/E7.
      We provide in vitro (knockdown/over-expression in mammalian cells) and in vivo
      (genetic manipulation in Drosophila) evidence for an endogenous role of UBE3A in
      regulating circadian dynamics and rhythmic locomotor behaviour. Together, our
      data reveal an essential and conserved role of UBE3A in the regulation of the
      circadian system in mammals and flies and identify a novel mechanistic link
      between oncogene E6/E7-mediated cell transformation and circadian (BMAL1)
      disruption. 

PMID- 24728991
TI  - Pervasive generation of oppositely oriented spacers during CRISPR adaptation.
AB  - During the process of prokaryotic CRISPR adaptation, a copy of a segment of
      foreign deoxyribonucleic acid referred to as protospacer is added to the CRISPR
      cassette and becomes a spacer. When a protospacer contains a neighboring target
      interference motif, the specific small CRISPR ribonucleic acid (crRNA)
      transcribed from expanded CRISPR cassette can protect a prokaryotic cell from
      virus infection or plasmid transformation and conjugation. We show that in
      Escherichia coli, a vast majority of plasmid protospacers generate spacers
      integrated in CRISPR cassette in two opposing orientations, leading to frequent
      appearance of complementary spacer pairs in a population of cells that underwent
      CRISPR adaptation. When a protospacer contains a spacer acquisition motif AAG,
      spacer orientation that generates functional protective crRNA is strongly
      preferred. All other protospacers give rise to spacers oriented in both ways at
      comparable frequencies. This phenomenon increases the repertoire of available
      spacers and should make it more likely that a protective crRNA is formed as a
      result of CRISPR adaptation. 

PMID- 24728992
TI  - Similarity in targets with REST points to neural and glioblastoma related miRNAs.
AB  - There are groups of genes that need coordinated repression in multiple contexts,
      for example if they code for proteins that work together in a pathway or in a
      protein complex. Redundancy of biological regulatory networks implies that such
      coordinated repression might occur at both the pre- and post-transcriptional
      level, though not necessarily simultaneously or under the same conditions. Here,
      we propose that such redundancy in the global regulatory network can be detected
      by the overlap between the putative targets of a transcriptional repressor, as
      identified by a ChIP-seq experiment, and predicted targets of a microRNA (miRNA).
      To test this hypothesis, we used publicly available ChIP-seq data of the neural
      transcriptional repressor RE1 silencing transcription factor (REST) from 15
      different cell samples. We found 20 miRNAs, each of which shares a significant
      amount of predicted targets with REST. The set of predicted associations between
      these 20 miRNAs and the overlapping REST targets is enriched in known miRNA
      targets. Many of the detected miRNAs have functions related to neural identity
      and glioblastoma, which could be expected from their overlap in targets with
      REST. We propose that the integration of experimentally determined transcription
      factor binding sites with miRNA-target predictions provides functional
      information on miRNAs. 

PMID- 24728993
TI  - CDK2-dependent phosphorylation of Suv39H1 is involved in control of
      heterochromatin replication during cell cycle progression.
AB  - Although several studies have suggested that the functions of heterochromatin
      regulators may be regulated by post-translational modifications during cell cycle
      progression, regulation of the histone methyltransferase Suv39H1 is not fully
      understood. Here, we demonstrate a direct link between Suv39H1 phosphorylation
      and cell cycle progression. We show that CDK2 phosphorylates Suv39H1 at Ser391
      and these phosphorylation levels oscillate during the cell cycle, peaking at S
      phase and maintained during S-G2-M phase. The CDK2-mediated phosphorylation of
      Suv39H1 at Ser391 results in preferential dissociation from chromatin.
      Furthermore, phosphorylation-mediated dissociation of Suv39H1 from chromatin
      causes an enhanced occupancy of JMJD2A histone demethylase on heterochromatin and
      alterations in inactive histone marks. Overexpression of phospho-mimic Suv39H1
      induces early replication of heterochromatin, suggesting the importance of
      Suv39H1 phosphorylation in the replication of heterochromatin. Moreover,
      overexpression of phospho-defective Suv39H1 caused altered replication timing of
      heterochromatin and increases sensitivity to replication stress. Collectively,
      our data suggest that phosphorylation-mediated modulation of Suv39H1-chromatin
      association may be an initial step in heterochromatin replication. 

PMID- 24728994
TI  - The DynaMine webserver: predicting protein dynamics from sequence.
AB  - Protein dynamics are important for understanding protein function. Unfortunately,
      accurate protein dynamics information is difficult to obtain: here we present the
      DynaMine webserver, which provides predictions for the fast backbone movements of
      proteins directly from their amino-acid sequence. DynaMine rapidly produces a
      profile describing the statistical potential for such movements at residue-level
      resolution. The predicted values have meaning on an absolute scale and go beyond
      the traditional binary classification of residues as ordered or disordered, thus
      allowing for direct dynamics comparisons between protein regions. Through this
      webserver, we provide molecular biologists with an efficient and easy to use tool
      for predicting the dynamical characteristics of any protein of interest, even in
      the absence of experimental observations. The prediction results are visualized
      and can be directly downloaded. The DynaMine webserver, including instructive
      examples describing the meaning of the profiles, is available at
      http://dynamine.ibsquare.be. 

PMID- 24728995
TI  - Intrinsic stability and oligomerization dynamics of DNA processivity clamps.
AB  - Sliding clamps are ring-shaped oligomeric proteins that are essential for
      processive deoxyribonucleic acid replication. Although crystallographic
      structures of several clamps have been determined, much less is known about clamp
      structure and dynamics in solution. Here, we characterized the intrinsic solution
      stability and oligomerization dynamics of the homodimeric Escherichia coli beta
      and the homotrimeric Saccharomyces cerevisiae proliferating cell nuclear antigen
      (PCNA) clamps using single-molecule approaches. We show that E. coli beta is
      stable in solution as a closed ring at concentrations three orders of magnitude
      lower than PCNA. The trimeric structure of PCNA results in slow subunit
      association rates and is largely responsible for the lower solution stability.
      Despite this large difference, the intrinsic lifetimes of the rings differ by
      only one order of magnitude. Our results show that the longer lifetime of the E.
      coli beta dimer is due to more prominent electrostatic interactions that
      stabilize the subunit interfaces. 

PMID- 24728996
TI  - Telomere length kinetics assay (TELKA) sorts the telomere length maintenance
      (tlm) mutants into functional groups.
AB  - Genome-wide systematic screens in yeast have uncovered a large gene network (the
      telomere length maintenance network or TLM), encompassing more than 400 genes,
      which acts coordinatively to maintain telomere length. Identifying the genes was
      an important first stage; the next challenge is to decipher their mechanism of
      action and to organize then into functional groups or pathways. Here we present a
      new telomere-length measuring program, TelQuant, and a novel assay, telomere
      length kinetics assay, and use them to organize tlm mutants into functional
      classes. Our results show that a mutant defective for the relatively unknown MET7
      gene has the same telomeric kinetics as mutants defective for the ribonucleotide
      reductase subunit Rnr1, in charge of the limiting step in dNTP synthesis, or for
      the Ku heterodimer, a well-established telomere complex. We confirm the epistatic
      relationship between the mutants and show that physical interactions exist
      between Rnr1 and Met7. We also show that Met7 and the Ku heterodimer affect dNTP
      formation, and play a role in non-homologous end joining. Thus, our telomere
      kinetics assay uncovers new functional groups, as well as complex genetic
      interactions between tlm mutants. 

PMID- 24728997
TI  - KDM4C (GASC1) lysine demethylase is associated with mitotic chromatin and
      regulates chromosome segregation during mitosis.
AB  - Various types of human cancers exhibit amplification or deletion of KDM4A-D
      members, which selectively demethylate H3K9 and H3K36, thus implicating their
      activity in promoting carcinogenesis. On this basis, it was hypothesized that
      dysregulated expression of KDM4A-D family promotes chromosomal instabilities by
      largely unknown mechanisms. Here, we show that unlike KDM4A-B, KDM4C is
      associated with chromatin during mitosis. This association is accompanied by a
      decrease in the mitotic levels of H3K9me3. We also show that the C-terminal
      region, containing the Tudor domains of KDM4C, is essential for its association
      with mitotic chromatin. More specifically, we show that R919 residue on the
      proximal Tudor domain of KDM4C is critical for its association with chromatin
      during mitosis. Interestingly, we demonstrate that depletion or overexpression of
      KDM4C, but not KDM4B, leads to over 3-fold increase in the frequency of abnormal
      mitotic cells showing either misaligned chromosomes at metaphase, anaphase
      telophase lagging chromosomes or anaphase-telophase bridges. Furthermore,
      overexpression of KDM4C demethylase-dead mutant has no detectable effect on
      mitotic chromosome segregation. Altogether, our findings implicate KDM4C
      demethylase activity in regulating the fidelity of mitotic chromosome segregation
      by a yet unknown mechanism. 

PMID- 24728998
TI  - Classification and evolution of type II CRISPR-Cas systems.
AB  - The CRISPR-Cas systems of archaeal and bacterial adaptive immunity are classified
      into three types that differ by the repertoires of CRISPR-associated (cas) genes,
      the organization of cas operons and the structure of repeats in the CRISPR
      arrays. The simplest among the CRISPR-Cas systems is type II in which the
      endonuclease activities required for the interference with foreign
      deoxyribonucleic acid (DNA) are concentrated in a single multidomain protein,
      Cas9, and are guided by a co-processed dual-tracrRNA:crRNA molecule. This compact
      enzymatic machinery and readily programmable site-specific DNA targeting make
      type II systems top candidates for a new generation of powerful tools for genomic
      engineering. Here we report an updated census of CRISPR-Cas systems in bacterial
      and archaeal genomes. Type II systems are the rarest, missing in archaea, and
      represented in ~ 5% of bacterial genomes, with an over-representation among
      pathogens and commensals. Phylogenomic analysis suggests that at least three cas
      genes, cas1, cas2 and cas4, and the CRISPR repeats of the type II-B system were
      acquired via recombination with a type I CRISPR-Cas locus. Distant homologs of
      Cas9 were identified among proteins encoded by diverse transposons, suggesting
      that type II CRISPR-Cas evolved via recombination of mobile nuclease genes with
      type I loci.

PMID- 24728999
TI  - Evidence for risk reduction among amphetamine-injecting men who have sex with
      men; results from national HIV behavioral surveillance surveys in the Seattle
      area 2008-2012.
AB  - In the Seattle area men who have sex with men and also inject amphetamines
      (amphetamine-injecting MSM/IDU) are disproportionately likely to be infected with
      HIV. To characterize their distinctive characteristics, we combined data from two
      Seattle-area surveys of men who have sex with men (MSM) and two surveys of
      injection drug users (IDU). Amphetamine-injecting MSM/IDU were compared with:
      male IDU, MSM and other MSM/IDU. Amphetamine-injecting MSM/IDU were older than
      MSM but younger than IDU, more likely to be white than either group, and had an
      educational level higher than IDU but below MSM. They had the highest HIV
      prevalence (56 vs. 4-19 %). However, reported HIV cases among them fell from 92
      in 1990 to 25 in 2012. They were most likely to report ten or more sex partners
      (49 vs. 4-26 %), an STD diagnosis (22 vs. 1-7 %) and be tested for HIV (odds
      ratio 1.00 vs. 0.34-0.52), and least likely to share needles (odds ratio 1.00 vs.
      6.80-10.50). While sexual risk remains high, these data suggest measurable and
      effective risk reduction with respect to sharing injection equipment and HIV
      testing among Seattle-area amphetamine-injecting MSM/IDU.

PMID- 24729001
TI  - Retraction. Intracellular acidification triggered by mitochondrial-derived
      hydrogen peroxide is an effector mechanism for drug-induced apoptosis in tumor
      cells.

PMID- 24729000
TI  - Desirable possible selves and depression in adult women with eating disorders.
AB  - PURPOSE: Possible selves are conceptions of our selves in future states. Previous
      findings indicated that women with anorexia nervosa tended to have more negative
      possible selves than a control group, even when rating future situations normally
      regarded in our society as desirable. The present study investigated whether this
      was a general pattern in women with eating disorders, relating findings on
      possible selves to depression. Possible selves concerning treatment were also
      included. METHODS: Patients with anorexia nervosa (n = 19), bulimia nervosa (n =
      29) or an eating disorder not otherwise specified (EDNOS) (n = 18) and a control
      group (n = 27) rated the valence of five possible selves on Likert's scales.
      Levels of depression were measured among the patients using the Beck Depression
      Inventory. RESULTS: The patients rated the valence of the possible selves
      significantly less positively and more negatively than did the control group. A
      strong correlation between valence and depression was found in patients with
      anorexia nervosa and bulimia nervosa. No such correlation was found in patients
      with EDNOS. Possible selves concerning future treatment were rated even more
      negatively. CONCLUSIONS: The results indicate that, when compared to a non
      patient group, eating disorder patients make more negative evaluations of
      possible selves usually seen as desirable. Depression may be a mediating factor
      in these evaluations for the anorexia and bulimia patients.

PMID- 24729002
TI  - Are rice (Oryza sativa L.) phosphate transporters regulated similarly by
      phosphate and arsenate? A comprehensive study.
AB  - Rice is one of the most important staple foods worldwide, but it often contains
      inorganic arsenic, which is toxic and gives rise to severe health problems. Rice
      plants take up arsenate As(V) via the phosphate transport pathways, though it is
      not known how As(V), as compared to phosphate, modifies the expression of
      phosphate transporters (PTs). Therefore, the impact of As(V) or phosphate (Pi) on
      the gene expression of PTs and several Pi signaling regulators was investigated.
      Rice plants were grown on medium containing different As(V) or Pi concentrations.
      Growth was evaluated and the expression of tested genes was quantified at
      different time points, using quantitative RT-PCR (qPCR). The As and P content in
      plants was determined using inductively coupled plasma mass spectrometry (ICP
      MS). As(V) elicited diverse and opposite responses of different PTs in roots and
      shoots, while Pi triggered a more shallow and uniform transcriptional response in
      several tested genes. Only a restricted set of genes, including PT2, PT3, PT5 and
      PT13 and two SPX-MFS family members, was particularly responsive to As(V).
      Despite some common reactions, the responses of the analyzed genes were
      predominantly ion-specific. The possible reasons and consequences are discussed. 

PMID- 24729003
TI  - Determinants of delay in seeking malaria treatment for children under-five years
      in parts of South Eastern Nigeria.
AB  - One of the components of the current WHO strategy to fight malaria is early
      recognition and prompt and appropriate treatment. We investigated determinants of
      delay in seeking early and appropriate malaria treatment for children (0-5 years)
      in Ohaji/Egbema, South Eastern Nigeria. Data was collected using structured pre
      tested questionnaires elicited in the local language (Igbo) to 738 consenting
      mothers within the child bearing age (15-49 years). About twenty-two percent
      (22%) of the respondents sought treatment within 24 h for their children with
      malaria and were excluded from further investigation. More than half of the
      remaining respondents (51.5%) delayed in seeking treatment because they had to
      watch their children for some days, while 21.4% were due to financial
      difficulties. The age, parity, marital status/type of marriage and educational
      attainment of the mothers including family social-economic status were found to
      be statistically related to delay in seeking appropriate treatment (P < 0.05).
      Wrong first line treatment choices by the respondents also contributed to this
      delay. These results underscore the need to improve awareness of mothers and
      caregivers on the need and ways of seeking early, appropriate and effective
      treatment for their children who have malaria. This is very important if the WHO
      strategy of early recognition, prompt and appropriate treatment is to be
      effective so as to sufficiently reduce mortality and morbidity due to malaria
      among children in endemic rural areas. It will also aid in the proper management
      and treatment of other childhood febrile illnesses.

PMID- 24729005
TI  - Initiation of Breastfeeding and Factors Associated with Prelacteal Feeds in
      Central Nepal.
AB  - BACKGROUND: Prelacteal feeds and delayed initiation of breastfeeding may lead to
      undernutrition of the infant but are still prevalent in many countries.
      OBJECTIVE: A prospective cohort community-based study was conducted in central
      Nepal to ascertain the rate of early breastfeeding initiation and factors
      associated with the introduction of prelacteal feeds. METHODS: Breastfeeding
      information was collected from 639 women who recently gave birth in the Kaski
      district of central Nepal. Backward stepwise logistic regression analysis was
      performed to determine factors associated with the use of prelacteal feeds.
      RESULTS: The incidence of prelacteal feeds was 9.1%, with infant formula being
      the most common prelacteal food. Approximately 67% and 90% of mothers breastfed
      within 1 hour and 4 hours of delivery, respectively. Women who reside in urban
      areas (odds ratio [OR] = 2.68; 95% confidence interval [CI], 1.35-5.39), first
      time mothers (OR = 2.15; 95% CI, 1.15-4.02), and those who underwent cesarean
      section (OR = 10.10; 95% CI, 5.47-18.67) were more likely to give prelacteal
      feeds to their infants. CONCLUSION: The early initiation of breastfeeding with
      colostrum as the first feed was common in the study area. The introduction of
      prelacteal feeds was associated with urban residency, first-time motherhood, and
      cesarean delivery.

PMID- 24729004
TI  - Transcriptional dynamics of bile salt export pump during pregnancy: mechanisms
      and implications in intrahepatic cholestasis of pregnancy.
AB  - Bile salt export pump (BSEP) is responsible for biliary secretion of bile acids,
      a rate-limiting step in the enterohepatic circulation of bile acids and
      transactivated by nuclear receptor farnesoid X receptor (FXR). Intrahepatic
      cholestasis of pregnancy (ICP) is the most prevalent disorder among diseases
      unique to pregnancy and primarily occurs in the third trimester of pregnancy,
      with a hallmark of elevated serum bile acids. Currently, the transcriptional
      regulation of BSEP during pregnancy and its underlying mechanisms and involvement
      in ICP are not fully understood. In this study the dynamics of BSEP transcription
      in vivo in the same group of pregnant mice before, during, and after gestation
      were established with an in vivo imaging system (IVIS). BSEP transcription was
      markedly repressed in the later stages of pregnancy and immediately recovered
      after parturition, resembling the clinical course of ICP in human. The
      transcriptional dynamics of BSEP was inversely correlated with serum 17beta
      estradiol (E2) levels before, during, and after gestation. Further studies showed
      that E2 repressed BSEP expression in human primary hepatocytes, Huh 7 cells, and
      in vivo in mice. Such transrepression of BSEP by E2 in vitro and in vivo required
      estrogen receptor alpha (ERalpha). Mechanistic studies with chromatin
      immunoprecipitation (ChIP), protein coimmunoprecipitation (Co-IP), and
      bimolecular fluorescence complementation (BiFC) assays demonstrated that ERalpha
      directly interacted with FXR in living cells and in vivo in mice. CONCLUSION:
      BSEP expression was repressed by E2 in the late stages of pregnancy through a
      nonclassical E2/ERalpha transrepressive pathway, directly interacting with FXR.
      E2-mediated repression of BSEP expression represents an etiological contributing
      factor to ICP and therapies targeting the ERalpha/FXR interaction may be
      developed for prevention and treatment of ICP.

PMID- 24729006
TI  - A systematic review of transoral robotic surgery and radiotherapy for early
      oropharynx cancer: a systematic review.
AB  - OBJECTIVES/HYPOTHESIS: To demonstrate the comparative effectiveness of transoral
      robotic surgery (TORS) to intensity modulated radiotherapy (IMRT) for early T
      stage oropharyngeal cancer. DATA SOURCES: The search included MEDLINE, EMBASE,
      CENTRAL, PsychInfo, CINAHL, and bibliographies of relevant studies through
      September 2012. METHODS: Studies included patients treated for early T-stage
      oropharynx cancer with TORS or IMRT. Study retrieval and data extraction were
      conducted in duplicate and resolved by consensus. Treatment- specific details, as
      well as recurrence, survival, and adverse events, were collected. Methodologic
      quality for each study was appraised. RESULTS: Twenty case series, including
      eight IMRT studies (1,287 patients) and 12 TORS studies (772 patients), were
      included. Patients receiving definitive IMRT also received chemotherapy (43%) or
      neck dissections for persistent disease (30%), whereas patients receiving TORS
      required adjuvant radiotherapy (26%) or chemoradiotherapy (41%). Two-year overall
      survival estimates ranged from 84% to 96% for IMRT and from 82% to 94% for TORS.
      Adverse events for IMRT included esophageal stenosis (4.8%), osteoradionecrosis
      (2.6%), and gastrostomy tubes (43%)-and adverse events for TORS included
      hemorrhage (2.4%), fistula (2.5%), and gastrostomy tubes at the time of surgery
      (1.4%) or during adjuvant treatment (30%). Tracheostomy tubes were needed in 12%
      of patients at the time of surgery, but most were decannulated prior to
      discharge. CONCLUSION: This review suggests that survival estimates are similar
      between the two modalities and that the differences lie in adverse events.

PMID- 24729010
TI  - The ferric iron chelator 2,2'-dipyridyl attenuates basilar artery vasospasm and
      improves neurological function after subarachnoid hemorrhage in rabbits.
AB  - We investigated the efficacy of the ferrous iron (Fe(2+)) chelator 2,2'-dipyridyl
      (DP) to attenuate cerebral vasospasm after subarachnoid hemorrhage (SAH). Thirty
      six New Zealand white rabbits were randomly assigned to four groups: untreated
      control, SAH, SAH + dimethyl sulfoxide (DMSO) vehicle, and SAH + DP. SAH was
      induced by injection of autologous blood into the cisterna magna and then DP or
      vehicle was infused into the cistern magna for 5 days (20 mg/kg/day or an equal
      volume of DMSO). Neurological deficit score (NDS) was used to assess neurological
      function and cerebral angiography to measure basilar artery (BA) diameter
      following SAH. TUNEL staining was used to detect BA endothelial cell apoptosis,
      and immunohistochemistry and Western blotting to assess changes in caspase-3
      protein levels 5 days post-SAH. The SAH + DP group had a significantly larger
      mean BA diameter and lower mean NDS post-SAH compared to the SAH + DMSO and SAH
      groups (p < 0.05). TUNEL-positive cell numbers and caspase-3 levels were
      significantly reduced in BA endothelial cells of the SAH + DP group as compared
      to the SAH and SAH + DMSO groups (p < 0.05). The iron chelator DP reduced
      vasospasm and neurological sequelae in rabbits, likely by chelating the Fe(2+) in
      oxyhemoglobin and reducing oxidative stress-induced endothelial cell apoptosis.

PMID- 24729011
TI  - Perihaematomal cytokine expression is a crucial component of intracerebral
      haemorrhage pathophysiology.

PMID- 24729012
TI  - Deciphering aggregates, prefibrillar oligomers and protofibrils of cytochrome c.
AB  - Aggregation of protein into insoluble intracellular complexes and inclusion
      bodies underlies the pathogenesis of human neurodegenerative diseases. Importance
      of cytochrome c (cyt c) arises from its involvement in apoptosis, sequence
      homology and for studying molecular evolution. A systemic investigation of
      polyethylene glycol (PEG) and trifluoroethanol (TFE) on the conformational
      stability of cyt c as a model hemeprotein was made using multi-methodological
      approach. Cyt c exists as molten globule (MG) at 60% PEG-400 and 40% TFE as
      confirmed by far-UV CD, attenuated total reflection Fourier transform infrared
      spectroscopy, Trp environment, 8-anilino-1-naphthalene-sulfonic acid (ANS)
      binding and blue shift in the soret band. Q-band splitting in MG states specifies
      conformational changes in the hydrophobic heme-binding pocket. Aggregates were
      detected at 90% PEG-400 and 50% TFE as confirmed by increase thioflavin T and ANS
      fluorescence and shift in Congo red absorbance. Detection of prefibrils and
      protofibrils at 90% PEG-400 and 50% TFE was possible after 72-h incubation.
      Single cell gel electrophoresis of prefibrils and protofibrils showed DNA damage
      confirming their toxicity and potential health hazards. Scanning electron
      microscopy and XRD analysis confirmed prefibrillar oligomers and protofibrils of
      cyt c.

PMID- 24729013
TI  - Insights into the molecular interactions between aminopeptidase and amyloid beta
      peptide using molecular modeling techniques.
AB  - Amyloid beta (Abeta) peptides play a central role in the pathogenesis of
      Alzheimer's disease. The accumulation of Abeta peptides in AD brain was caused
      due to overproduction or insufficient clearance and defects in the proteolytic
      degradation of Abeta peptides. Hence, Abeta peptide degradation could be a
      promising therapeutic approach in AD treatment. Recent experimental report
      suggests that aminopeptidase from Streptomyces griseus KK565 (SGAK) can degrade
      Abeta peptides but the interactive residues are yet to be known in detail at the
      atomic level. Hence, we developed the three-dimensional model of aminopeptidase
      (SGAK) using SWISS-MODEL, Geno3D and MODELLER. Model built by MODELLER was used
      for further studies. Molecular docking was performed between aminopeptidase
      (SGAK) with wild-type and mutated Abeta peptides. The docked complex of
      aminopeptidase (SGAK) and wild-type Abeta peptide (1IYT.pdb) shows more stability
      than the other complexes. Molecular docking and MD simulation results revealed
      that the residues His93, Asp105, Glu139, Glu140, Asp168 and His255 are involved
      in the hydrogen bonding with Abeta peptide and zinc ions. The interactions
      between carboxyl oxygen atoms of Glu139 of aminopeptidase (SGAK) with water
      molecule suggest that the Glu139 may be involved in the nucleophilic attack on
      Ala2-Glu3 peptide bond of Abeta peptide. Hence, amino acid Glu139 of
      aminopeptidase (SGAK) might play an important role to degrade Abeta peptides, a
      causative agent of Alzheimer's disease. 

PMID- 24729014
TI  - Through-and-through wire technique for endovascular damage control in traumatic
      proximal axillary artery transection.
AB  - Repair of blunt shoulder trauma with transection of the subclavian or proximal
      axillary artery poses a surgical challenge, especially in instable patients.
      Endovascular treatment for initial damage control in arterial transection has
      evolved as a promising technique to improve outcome, but technical success can be
      limited in cases of complete transection as the lesion cannot be passed by a
      guidewire. This report describes an endovascular approach using a through-and
      through brachial-femoral wire to control complete traumatic transection of the
      proximal axillary artery in a hemodynamically unstable patient. Endovascular
      therapy is used as a bridging method for open surgical repair three days later
      under optimized conditions with an interdisciplinary team. The brachial-femoral
      guidewire technique helps to overcome limitations in endovascular therapy in
      patients with blunt traumatic transection of thoracic outlet arteries. 

PMID- 24729015
TI  - A systematic review of psychological functioning of children exposed to HIV:
      using evidence to plan for tomorrow's HIV needs.
AB  - Prevention of mother to child transmission of HIV can virtually eliminate
      paediatric HIV infection. Studies are needed to understand child development
      outcomes for children exposed to HIV in utero but born HIV negative (HIV affected
      children). This systematic review examined cognitive, developmental and
      behavioural outcomes for HIV affected children compared to control unexposed and
      uninfected children. Key word searches of electronic databases generated 1,739
      hits and 11 studies with adequate quality design and measures of standardised
      cognitive, behavioural and developmental indices. Cognitive performance,
      behaviour and developmental delay were measured with 15 different standardised
      scales from 650 HIV affected children, 736 control children and 205 HIV positive
      children. Performance scores for HIV affected children were significantly lower
      than controls in at least one measure in 7/11 studies. An emerging pattern of
      delay seems apparent. HIV affected children will grow in number and their
      development needs to be monitored and provided for. 

PMID- 24729016
TI  - Fibroblast growth factor 23 (FGF23) and early chronic kidney disease in the
      elderly.
AB  - BACKGROUND: Better biomarkers of CKD reflecting responses to decreased glomerular
      filtration rate (GFR) are needed. We determined the value of estimated GFR (eGFR)
      as a threshold for the increase of plasma cFGF23 (C-terminal) and intact
      fibroblast growth factor-23 (iFGF23) (intact) concentrations in the course of
      chronic kidney disease (CKD) and compared this eGFR value with values related to
      increased serum intact parathyroid hormone (iPTH) or phosphorus concentrations in
      an elderly population. METHODS: We measured plasma iFGF23, cFGF23, serum
      phosphorus, calcium, albumin, creatinine, urea, cystatin C, iPTH and vitamin 25
      OH-D3 in 3780 population-based study participants aged >= 65 years. RESULTS:
      Serum phosphorus concentrations hardly increased until mean eGFR reached 47.3 +/-
      4.7 mL/min/1.73 m(2) but then increased exponentially. Similarly, both iPTH and
      iFGF23 increased slightly in early CKD but then increased exponentially when eGFR
      reached 55.0 +/- 4.2 mL/min/1.73 m(2) for iPTH and 51.6 +/- 5.7 mL/min/1.73 m(2)
      for iFGF23. The departure point for exponential increases in cFGF23 preceded
      those for iPTH and iFGF23 and occurred at a mean eGFR of 57.7 +/- 7.8 mL/min/1.73
      m(2). The prevalence of increased iFGF23 occurred at a remarkably higher eGFR
      value than that of cFGF23 across the CKD stages. CONCLUSIONS: The increase in
      cFGF23 preceded both the increase in iPTH and iFGF23 as eGFR declined. Increased
      plasma iFGF23 level did not precede the rise in serum iPTH concentrations and did
      not occur before stage-3 CKD in elderly persons. However, cFGF23 was not an early
      marker of CKD in the elderly subjects.

PMID- 24729018
TI  - Effects of NIPAm polymer additives on the enzymatic hydrolysis of Avicel and
      pretreated Miscanthus.
AB  - There is currently much interest in the economic use of cellulosic biomass as a
      source of renewable fuels. This process typically involves the enzymatic
      hydrolysis of plant matter to afford soluble sugars for subsequent fermentation
      steps. The cost of cellulase enzymes presents a critical barrier to the
      commercialization of these processes. In this work, we demonstrate that a new
      family of polymer additives based on NIPAm can increase enzyme performance
      substantially. When applied to an industrially relevant combination of enzymes
      and lignin-containing biomass, polymer additives allow a 60% reduction in enzyme
      loading to achieve the same level of saccharification. Evidence presented herein
      suggests that these polymers function through multiple mechanisms, including (1)
      preventing enzyme denaturation through shear and interfacial interactions, (2)
      preventing non-productive adsorption to lignin, and (3) altering the cellulose
      structure. An advantage of these polymers over other additives is their
      thermoresponsive behavior, enabling their recovery and reuse.

PMID- 24729019
TI  - An evaluation of the Cool 2 Be Safe program: an evidence-based community
      disseminated program to positively impact children's beliefs about injury risk on
      playgrounds.
AB  - Falls from playground equipment during play are a leading cause of injury for
      elementary school children. Changes to playground design and surfacing materials
      can reduce injury risk. However, there is also a need for intervention programs
      to reduce risky play behaviors by children that are associated with falls. The
      Cool 2 Be Safe program was developed based on past research that identified
      effective strategies for targeting injury beliefs that predict risk behaviors on
      playgrounds among individually tested elementary school children. The current
      study evaluated the effectiveness of delivering these activities as an integrated
      program and in a group format in after school programs organized by Boys and
      Girls Clubs of Canada. The clubs were provided all program and extensive training
      materials, and a webinar training session was conducted for facilitators.
      Observations of sessions provided data on fidelity of program delivery. Pre- and
      post-intervention data assessing children's injury beliefs were collected via
      survey, with children participating in four structured activity sessions in small
      groups between premeasures and post-measures. The training materials proved to be
      quite effective; observational data indicated 88 % compliance with the
      procedures. Comparing children's pre- and post-responses revealed positive
      changes in injury-risk beliefs that have been shown to predict reduced risk
      taking on playgrounds. This initial evaluation suggests that the Cool 2 Be Safe
      community program holds much promise as a means for addressing the issue of fall
      risk behaviors by elementary school children on playgrounds.

PMID- 24729021
TI  - A 30-year experience of Millin's retropubic prostatectomy: Has this classic
      operation derived by a President of the College in Ireland stood the test of
      time?
AB  - INTRODUCTION: In patients with large gland volume, open prostatectomy/adenoma
      enucleation remains a valuable surgical option in treating large obstructing
      prostates. We report our series of open prostatectomies spanning 32 years from a
      single institution. PATIENTS AND METHODS: We retrospectively reviewed all
      patients who underwent open prostatectomy between 1980 and 2012. Patient
      demographical, clinical, pre- and postoperative data and final histology were
      retrieved from hospital in-patient enquiry system and chart review. RESULTS: A
      total of 161 patients underwent Millin's prostatectomy by seven surgeons between
      1980 and 2012. The mean blood loss was 1,381 mls (range 300-3,675 mls). One-third
      (34%) of patients (n = 55) received a blood transfusion. The mean weight of
      prostate tissue removed was 119 g (median 112 g, range 17-372 g). 6.6 % of
      pathological specimens revealed incidental prostate cancer, of which 78% were
      well differentiated (Gleason score <= 6). The mean weight of prostate tissue
      removed in patients who received a transfusion was 124 g. Trial of micturition
      (TOM) was performed at a mean of 9 days (median 9 days, range 5-25 days) with 94%
      of patients having a successful trial of voiding. 6% of cases early in the series
      failed to void initially, but did so at later removal of catheter while still in
      hospital. 45 patients (28%) of patients developed peri- or postoperative
      complications. There were three deaths (1.9%). CONCLUSION: Open Millin's
      prostatectomy popularized over half a century ago continues to be a valuable
      option for the surgical treatment of high-volume prostate glands with excellent
      outcomes for patients.

PMID- 24729022
TI  - Incidental detection of haemoglobin (Hb) variants during high performance liquid
      chromatography (HPLC) analysis of HbA1c: is it time for a standardised approach
      to reporting?
AB  - BACK GROUND: Haemoglobin (Hb) variants are genetic variations in the globin genes
      that code for an abnormal globin protein structure. The prevalence of Hb variants
      has increased in Ireland due to the number of emigrants from Africa and Southeast
      Asia. The rate of incidentally detected Hb variants, in laboratories employing
      HPLC to measure HbA1c, has increased in parallel. The presence of a Hb variant
      can compromise HbA1c measurement and interpretation. In such cases, HbA1c cannot
      be used to diagnose diabetes or to assess concordance with glycaemic targets.
      AIM: To establish the number of incidentally identified Hb variants during 10
      months of routine HbA1c analysis, and the percentage of HbA1c reports alerting
      the requesting clinician to the presence of a Hb variant. METHODS: The laboratory
      database was interrogated to extract all records of HbA1c requests and
      incidentally identified Hb variants from March to December 2012. RESULTS: A total
      of 32,636 HbA1c analyses were performed during the evaluation period. Seventy
      three Hb variants were identified in a total of 46 patients. In 32.6% (15 of 46)
      the haemoglobinopathy status was known prior to testing and 97% of HbA1c reports
      communicated the presence of the Hb variant to the requesting clinician.
      CONCLUSION: Hb variants may invalidate the results of HbA1c analysis and could
      result in a missed diagnosis or a misdiagnosis of diabetes or mismanagement of a
      patient with diabetes mellitus. It is, therefore, imperative that a comment
      alerting the requesting clinician to the presence of the Hb variant is appended
      to the HbA1c result.

PMID- 24729020
TI  - Inhibition of Integrin-HER2 signaling by Cucurbitacin B leads to in vitro and in
      vivo breast tumor growth suppression.
AB  - HER2, an oncogenic receptor is overexpressed in about 25-30% of breast cancer
      patients. HER2 has been shown to play role in tumor promotion by having cross
      talk with multiple oncogenic pathways in cancer cells. Our results show that
      Cucurbitacin B (CuB), a triterpenoid steroidal compound inhibited the growth of
      various breast cancer cells with an IC50 ranging from 18-50nM after 48 and 72 h
      of treatment. Our study also revealed the significant inhibitory effects of CuB
      on HER2 and integrin signaling in breast cancer. Notably, CuB inhibited ITGA6 and
      ITGB4 (integrin alpha6 and integrin beta4), which are overexpressed in breast
      cancer. Furthermore, CuB also induced the expression of major ITGB1and ITGB3,
      which are known to cause integrin-mediated cell death. In addition, we observed
      that TGFbeta treatment resulted in the increased association of HER2 with ITGA6
      and this association was inhibited by CuB treatment. Efficacy of CuB was tested
      in vivo using two different orthotopic models of breast cancer. MDA-MB-231 and 4T
      1 cells were injected orthotopically in the mammary fat pad of female athymic
      nude mice or BALB/c mice respectively. Our results showed that CuB administration
      inhibited MDA-MB-231 orthotopic tumors by 55%, and 4T-1 tumors by 40%. The 4T-1
      cells represent stage IV breast cancer and form very aggressive tumors. CuB
      mediated breast tumor growth suppression was associated with the inhibition of
      HER2/integrin signaling. Our results suggest novel targets of CuB in breast
      cancer in vitro and in vivo. 

PMID- 24729023
TI  - Attitudes among junior doctors towards improving the transurethral
      catheterisation process.
AB  - OBJECTIVES: To evaluate the subjective opinions of junior doctors on their
      adequacy of training and confidence levels for performing transurethral
      catheterisation (TUC) and to investigate their subjective interest in a 'safety
      mechanism' that would eliminate the potential for urethral trauma during TUC.
      METHODS: An anonymous online survey was emailed to all interns that had a
      documented email address on the Royal College of Surgeons Ireland registry (2012
      2013). The survey consisted of eight questions pertaining to TUC of male
      patients. RESULTS: The survey was delivered to 252 email addresses and the
      response rate was 52% (130/252). The vast majority (99%; n = 128) of interns felt
      confident inserting a transurethral catheter independently and 73% (n = 95)
      subjectively received appropriate training for catheterising male patients. The
      incidence of trauma after mistakenly inflating the catheter's anchoring balloon
      in the urethra was 3% (n = 4). The majority (90%; n = 116) of respondents were
      interested in a safety mechanism for preventing urethral trauma and 71% (n = 92)
      felt that a safety mechanism for urethral trauma prevention should be compulsory
      for all transurethral catheterisation among male patients. CONCLUSION: Despite
      pre-emptive training programmes, it appears that iatrogenic urethral trauma
      secondary to TUC remains a persistent morbidity in healthcare settings. Designing
      a safer transurethral catheter may be necessary to eliminate the risk of
      unnecessary urethral trauma in patients.

PMID- 24729024
TI  - Design, development and demonstration of an improved bird washing machine.
AB  - Since oil was first extracted, pollution of the seas and oceans or adjacent
      coasts has been an obstacle for the oil industry and environmental activists. The
      major concern is oil discharge into the water which may lead to birds' affliction
      or death, besides putting marine life in jeopardy. This paper presents the first
      description of the design and implementation of a new bird washing machine that
      can be utilized for cleaning of oil-coated birds with the minimum of stress. The
      machine is equipped with a pneumatic system comprised of 19 moving nozzles which
      evenly cover the bird's body and is designed to be used in contaminated
      environments where a vast number of birds are affected. Experimental trials show
      an improvement in operation efficiency compared to other methods in a reduction
      in washing time, energy consumption and a decrease in fatality rate of washed
      birds. 

PMID- 24729025
TI  - Transnational quarantine rhetorics: public mobilization in SARS and in H1N1 flu.
AB  - This essay examines how Chinese governments, local communities, and overseas
      Chinese in North America responded to the perceived health risks of Severe Acute
      Respiratory Syndrome (SARS) and H1N1 flu through the use of public and
      participatory rhetoric about risk and quarantines. Focusing on modes of security
      and quarantine practices, I examine how globalization and the social crises
      surrounding SARS and H1N1 flu operated to regulate differently certain bodies and
      areas. I identify three types of quarantines (mandatory, voluntary, and coerced)
      and conduct a transnational comparative analysis to investigate the relationships
      among quarantines, rhetoric, and public communication. I argue that health
      authorities must openly acknowledge the legitimacy of public input and actively
      seek public support regarding health crises. Only by collaborating with concerned
      communities and citizens and by providing careful guidance for public
      participation can health institutions ensure the efficacy of quarantine orders
      during emerging epidemics. 

PMID- 24729026
TI  - Acute myocardial infarction and 30-year coronary aneurysm follow-up by serial
      angiography in a young adult with Kawasaki disease.
AB  - The number of adult patients with coronary artery disease caused by Kawasaki
      disease (KD) is gradually increasing, but some patients drop out of clinical
      follow-up. However, careful, long-term follow-up and establishment of an optimal
      treatment strategy are needed in these patients, as well as cooperation between
      pediatric and adult cardiologists. We report a case of acute myocardial
      infarction in a young adult patient with KD whose serial coronary angiography was
      followed up for over 30 years. Successful reperfusion therapy was performed with
      thrombus aspiration, rotational atherectomy, and implantation of a drug-eluting
      stent.

PMID- 24729027
TI  - Stent intussusception after thromboaspiration through a platinum chrome stent: a
      particular case of longitudinal stent deformation.
AB  - The need to improve stent deliverability has led to the development of thinner
      and more flexible stents. However, there is concern about decreased longitudinal
      strength. The number of longitudinal stent deformation reports has dramatically
      increased. We report a case of stent longitudinal deformation after
      thromboaspiration through a new generation platinum chrome bare metal stent.
      Images show an "intussusception effect," an extreme form of the previously
      described "concertina deformation," as the mechanism of shortening. Since stent
      technology is constantly evolving, newer devices will probably be designed to
      have less susceptibility to longitudinal stent deformation. 

PMID- 24729028
TI  - Human placental extract reduces allergic inflammation in a murine allergic
      rhinitis model.
AB  - OBJECTIVES/HYPOTHESIS: In this study, we addressed the immunotherapeutic
      potential of human placental extract (HPE) in a murine allergic rhinitis (AR)
      model and explored its immunological mechanisms. STUDY DESIGN: In vivo study
      using an animal model. METHODS: HPE was administered to BALB/c mice before
      sensitization with allergen (Dermatophagoides farinae [Derf]) (pre-S group) or
      after allergen challenge (post-C group). The groups were compared with Derf
      treated mice that received no HPE (Derf group) and phosphate buffered saline
      (PBS)-treated mice (control). Allergic symptom scores, eosinophil counts, and
      serum Derf-specific IgE levels were measured. mRNA expression levels of
      interferon (IFN)-gamma, T-bet, interleukin (IL)-4, GATA-3, and Foxp3 in nasal
      mucosa were determined by real-time polymerase chain reaction. IFN-gamma, T-bet,
      IL-4, and GATA-3 were confirmed by Western blotting analysis. Spleen CD4(+)
      CD25(+) Foxp3(+) T cells were detected using flow cytometry. RESULTS: Rubbing
      motions, serum Derf-specific IgE, GATA-3 mRNA levels, IL-4 mRNA levels, and
      tissue eosinophil counts were decreased in both pre-S and post-C groups (all P <
      0.05). Western blots showed decreased expression of GATA-3 and IL-4 in both pre-S
      and post-C groups as compared to the Derf group. An increased percentage of
      CD4(+) CD25(+) Foxp3(+) T cells and an increased level of Foxp3 mRNA were found
      in pre-S and post-C groups as compared to those in the Derf group (all P < 0.05).
      CONCLUSION: Both prophylactic and therapeutic treatments with HPE significantly
      reduced allergic inflammation in nasal mucosa and had the potential to induce
      regulatory T cells in a murine model of AR.

PMID- 24729030
TI  - Cone photoreceptor definition on adaptive optics retinal imaging.
AB  - AIMS: To quantitatively analyse cone photoreceptor matrices on images captured on
      an adaptive optics (AO) camera and assess their correlation to well-established
      parameters in the retinal histology literature. METHODS: High resolution retinal
      images were acquired from 10 healthy subjects, aged 20-35 years old, using an AO
      camera (rtx1, Imagine Eyes, France). Left eye images were captured at 5 degrees 
      of retinal eccentricity, temporal to the fovea for consistency. In three
      subjects, images were also acquired at 0, 2, 3, 5 and 7 degrees  retinal
      eccentricities. Cone photoreceptor density was calculated following manual and
      automated counting. Inter-photoreceptor distance was also calculated. Voronoi
      domain and power spectrum analyses were performed for all images. RESULTS: At 5
      degrees  eccentricity, the cone density (cones/mm(2) mean+/-SD) was 15.3+/
      1.4*10(3) (automated) and 13.9+/-1.0*10(3) (manual) and the mean inter
      photoreceptor distance was 8.6+/-0.4 MUm. Cone density decreased and inter
      photoreceptor distance increased with increasing retinal eccentricity from 2 to 7
      degrees . A regular hexagonal cone photoreceptor mosaic pattern was seen at 2, 3
      and 5 degrees  of retinal eccentricity. CONCLUSIONS: Imaging data acquired from
      the AO camera match cone density, intercone distance and show the known features
      of cone photoreceptor distribution in the pericentral retina as reported by
      histology, namely, decreasing density values from 2 to 7 degrees  of eccentricity
      and the hexagonal packing arrangement. This confirms that AO flood imaging
      provides reliable estimates of pericentral cone photoreceptor distribution in
      normal subjects.

PMID- 24729031
TI  - Reducing the clinical burden of ranibizumab treatment for neovascular age-related
      macular degeneration using an individually planned regimen.
AB  - AIMS: The purpose of this study was to clinically validate an individually
      planned treatment regimen for neovascular age-related macular degeneration
      (nAMD), termed, observe and plan. This regimen was based on the predictability of
      an individual's need for retreatment and aimed to reduce the clinical burden,
      while obtaining good functional results. METHODS: This was a prospective case
      series that included 104 patients (115 eyes) with treatment-naive nAMD. Following
      three loading doses of ranibizumab, monthly observation visits allowed the
      disease recurrence interval to be determined. The recurrence interval was reduced
      by 2 weeks to give the retreatment interval for the next three injections.
      Periodical control visits (at least every 6 months) allowed the effectiveness of
      the treatment to be assessed and individual intervals adjusted. RESULTS: Mean
      visual acuity (VA) improved by 8.7 and 9.8 letters in months 3 and 12,
      respectively. The mean number of injections during the 12-month study was 7.8,
      while the mean number of ophthalmic examinations between months 3 and 12 was
      3.97. The mean treatment interval after the loading doses was 1.97 months.
      CONCLUSIONS: The observe-and-plan regimen significantly improved VA. This was
      obtained with fewer clinic visits compared with other regimens, which could ease
      the burden of nAMD treatment. TRIAL REGISTRATION NUMBER: Commission cantonale
      (VD) d'ethique de la recherche Clinique, Universite de Lausanne, Protocole
      351/11.

PMID- 24729033
TI  - A novel processing system of sterol regulatory element-binding protein-1c
      regulated by polyunsaturated fatty acid.
AB  - The proteolytic cascade is the key step in transactivation of sterol regulatory
      element-binding proteins (SREBPs), a transcriptional factor of lipid synthesis.
      Proteolysis of SREBP-2 is strictly regulated by sterols, but that of SREBP-1c was
      not strongly sterol-regulated, but inhibited by polyunsaturated fatty acids
      (PUFAs). In this study, the proteolytic processing of SREBP-1 and -2 was examined
      by transfection studies of cDNA-encoding mutants in which all the known cleavage
      sites were disrupted. In cultured cells, sterol-regulated SREBP-2 processing was
      completely eliminated by mutation of cleavage sites. In contrast, the
      corresponding SREBP-1c mutants as well as wild type exhibited large amounts of
      cleaved products in the nuclear extracts from culture cells and murine liver in
      vivo. The nuclear form of the mutant SREBP-1c was induced by delipidated
      condition and suppressed by eicosapentaenoic acid, an n-3 PUFA, but not by
      sterols. This novel processing mechanism was affected by neither SREBP cleavage
      activating protein (SCAP) nor insulin-induced gene (Insig)-1, unlike SREBP-2, but
      abolished by a serine protease inhibitor. Through analysis of deletion mutant, a
      site-2 protease recognition sequence (DRSR) was identified to be involved in this
      novel processing. These findings suggest that SREBP-1c cleavage could be
      subjected to a novel PUFA-regulated cleavage system in addition to the sterol
      regulatory SCAP/Insig system. 

PMID- 24729035
TI  - Splintage in the treatment of sagittal band incompetence and extensor tendon
      subluxation.
AB  - This study assessed the success of splintage for traumatic and atraumatic
      sagittal band incompetence and its relationship to the duration of symptoms
      before treatment. A retrospective review of all patients with sagittal band
      incompetence treated with splintage was performed. All patients had extensor
      tendon subluxation on physical examination. Ninety-two patients were included: 68
      traumatic and 24 atraumatic. Subluxation resolved with splintage in 77 patients.
      Traumatic tendon subluxation resolved in 95% of acute injuries, 100% of subacute
      injuries, and 67% of chronic injures. Atraumatic tendon subluxation resolved in
      100% of patients with acute presentation, 67% of patients with subacute
      presentation, and 57% of patients with chronic presentation. Surgery was rarely
      required. Splintage proved very effective for acute sagittal band incompetence,
      regardless of causation, but decreased in efficiency with chronicity. LEVEL OF
      EVIDENCE: Level 4.

PMID- 24729034
TI  - A pilot study linking reduced fronto-Striatal recruitment during reward
      processing to persistent bingeing following treatment for binge-eating disorder.
AB  - OBJECTIVE: The primary purpose of this study was to examine neurobiological
      underpinnings of reward processing that may relate to treatment outcome for binge
      eating disorder (BED). METHOD: Prior to starting treatment, 19 obese persons
      seeking treatment for BED performed a monetary incentive delay task during
      functional magnetic resonance imaging (fMRI). Analyses examined how the neural
      correlates of reward processing related to binge-eating status after 4-months of
      treatment. RESULTS: Ten individuals continued to report binge-eating (BEpost-tx )
      following treatment and 9 individuals did not (NBEpost-tx ). The groups did not
      differ in body mass index. The BEpost-tx group relative to the NBEpost-tx group
      showed diminished recruitment of the ventral striatum and the inferior frontal
      gyrus during the anticipatory phase of reward processing and reduced activity in
      the medial prefrontal cortex during the outcome phase of reward processing.
      DISCUSSION: These results link brain reward circuitry to treatment outcome in BED
      and suggest that specific brain regions underlying reward processing may
      represent important therapeutic targets in BED.

PMID- 24729036
TI  - Images in endocrine pathology: similar, but not the same!

PMID- 24729037
TI  - Working formulation of neuroendocrine tumors of the skin and breast.
AB  - In the skin and breast, endocrine tumors are composed of a heterogeneous mixture
      of endocrine and exocrine cells. The definition of "pure" endocrine carcinomas is
      a matter for debate, and as a consequence, there is lack of uniform diagnostic
      criteria. There are no significant clinical differences in either overall or
      disease-free survival between matched neoplasms with endocrine and without
      endocrine differentiation nor between the degree of endocrine differentiation and
      tumor size, stage, or prevalence of vascular invasion for both sites (skin and
      breast). Here, endocrine tumors of the skin and breast are grouped respectively
      into three categories that include most of the neuroendocrine tumors of the skin
      and breast as seen in routine practice. It was felt that the number of different
      types of neuroendocrine tumors is so conspicuous that it is impossible to
      organize them in an orderly classification. It has been proposed therefore, for
      practical diagnostic routine purposes, to arrange these neoplasms into a working
      formulation. The latter includes heterogeneous lesions respectively of the skin
      and breast within the same group that have clinical features in common. 

PMID- 24729038
TI  - Biofilms of Candida albicans serotypes A and B differ in their sensitivity to
      photodynamic therapy.
AB  - Candida albicans is classified into different serotypes according to cell wall
      mannan composition and cell surface hydrophobicity. Since the effectiveness of
      photodynamic therapy (PDT) depends on the cell wall structure of microorganisms,
      the objective of this study was to compare the sensitivity of in vitro biofilms
      of C. albicans serotypes A and B to antimicrobial PDT. Reference strains of C.
      albicans serotype A (ATCC 36801) and serotype B (ATCC 36802) were used for the
      assays. A gallium-aluminum-arsenide laser (660 nm) was used as the light source
      and methylene blue (300 MUM) as the photosensitizer. After biofilm formation on
      the bottom of a 96-well microplate for 48 h, each Candida strain was submitted to
      assays: PDT consisting of laser and photosensitizer application (L + P+), laser
      application alone (L + P-), photosensitizer application alone (L-P+), and
      application of saline as control (L-P-). After treatment, biofilm cells were
      scraped off and transferred to tubes containing PBS. The content of the tubes was
      homogenized, diluted, and seeded onto Sabouraud agar plates to determine the
      number of colony-forming units (CFU/mL). The results were compared by analysis of
      variance and Tukey test (p < 0.05). The two strains studied were sensitive to PDT
      (L + P+), with a log reduction of 0.49 for serotype A and of 2.34 for serotype B.
      Laser application alone only reduced serotype B cells (0.53 log), and the use of
      the photosensitizer alone had no effect on the strains tested. It can be
      concluded that in vitro biofilms of C. albicans serotype B were more sensitive to
      PDT.

PMID- 24729039
TI  - Effect of iron status in rats on the absorption of metal ions from plant
      ferritin.
AB  - An isolate of lead-ferritin obtained from soybean seeds sprouted in 25 mM of
      PbNO3 was introduced into the diet of both iron-deficient and iron non-deficient
      male rats. After a 21-day administration period, statistical differences in the
      lead accumulation in the femurs of the rats were noted. Iron-deficient rats
      accumulated more than four times the amount of lead in their bones than rats
      without iron-deficiency. No further decrease was observed in haemoglobin
      concentrations in the groups of animals fed with lead isolates, either iron
      deficient or iron non-deficient. Also, no differences in the mean corpuscular
      haemoglobin (MCH) and mean corpuscular volume (MCV) were observed at the end of
      the experiment in the group of iron non-deficient rats fed with lead-ferritin
      isolate compared to the control group of iron non-deficient rats. In the iron
      deficient group fed with lead-ferritin isolate, a small increase in haemoglobin
      concentrations, MCH, MCV and mean corpuscular haemoglobin concentrations (MCHC)
      was recorded. The results presented in this paper confirm that lead from the
      tested preparation-lead ferritin isolate-was better absorbed by those rats with
      induced iron deficiency anaemia. Additionally, we may also suspect based on the
      obtained results that absorption of ferritin-iron depends on iron status in the
      body. 

PMID- 24729040
TI  - Reference and counter electrode positions affect electrochemical characterization
      of bioanodes in different bioelectrochemical systems.
AB  - The placement of the reference electrode (RE) in various bioelectrochemical
      systems is often varied to accommodate different reactor configurations. While
      the effect of the RE placement is well understood from a strictly
      electrochemistry perspective, there are impacts on exoelectrogenic biofilms in
      engineered systems that have not been adequately addressed. Varying distances
      between the working electrode (WE) and the RE, or the RE and the counter
      electrode (CE) in microbial fuel cells (MFCs) can alter bioanode characteristics.
      With well-spaced anode and cathode distances in an MFC, increasing the distance
      between the RE and anode (WE) altered bioanode cyclic voltammograms (CVs) due to
      the uncompensated ohmic drop. Electrochemical impedance spectra (EIS) also
      changed with RE distances, resulting in a calculated increase in anode resistance
      that varied between 17 and 31 Omega (-0.2 V). While WE potentials could be
      corrected with ohmic drop compensation during the CV tests, they could not be
      automatically corrected by the potentiostat in the EIS tests. The electrochemical
      characteristics of bioanodes were altered by their acclimation to different anode
      potentials that resulted from varying the distance between the RE and the CE
      (cathode). These differences were true changes in biofilm characteristics because
      the CVs were electrochemically independent of conditions resulting from changing
      CE to RE distances. Placing the RE outside of the current path enabled accurate
      bioanode characterization using CVs and EIS due to negligible ohmic resistances
      (0.4 Omega). It is therefore concluded for bioelectrochemical systems that when
      possible, the RE should be placed outside the current path and near the WE, as
      this will result in more accurate representation of bioanode characteristics.

PMID- 24729042
TI  - Quality of care for Medicaid-enrolled youth with bipolar disorders.
AB  - This study examined conformance to clinical practice guidelines for children and
      adolescents with bipolar disorders and identified patient and provider factors
      associated with guideline concordant care. Administrative records were examined
      for 4,047 Medicaid covered youth aged 5-18 years with new episodes of bipolar
      disorder during 2006-2010. Main outcome measures included 5 claims-based quality
      of care measures reflecting national treatment guidelines. Measures addressed
      appropriate pharmacotherapy, therapeutic drug monitoring, and psychosocial
      treatment. The results indicated that current treatment practices for youth
      diagnosed with bipolar disorder typically fall short of recommended practice
      guidelines. Although the majority of affected youth are treated with recommended
      first-line pharmacotherapy, only a minority receive therapeutic drug monitoring
      and/or psychotherapy of recommended duration, underscoring the need for quality
      improvement initiatives. 

PMID- 24729041
TI  - The effect of everolimus on renal angiomyolipoma in patients with tuberous
      sclerosis complex being treated for subependymal giant cell astrocytoma: subgroup
      results from the randomized, placebo-controlled, Phase 3 trial EXIST-1.
AB  - BACKGROUND: Tuberous sclerosis complex (TSC) is characterized by benign tumours
      in multiple organs, including the brain, kidneys, skin, lungs and heart. Our
      objective was to evaluate everolimus, an mTOR inhibitor, in the treatment of
      angiomyolipoma in patients with subependymal giant cell astrocytoma (SEGA)
      associated with TSC. METHODS: EXamining everolimus In a Study of Tuberous
      Sclerosis Complex-1 (NCT00789828), a prospective, double-blind, randomized,
      placebo-controlled, Phase 3 study, examined everolimus in treating SEGA
      associated with TSC. Patients with serial SEGA growth from pre-baseline to
      baseline scans were randomly assigned (2:1) to receive 4.5 mg/m(2)/day everolimus
      (target blood trough: 5-15 ng/mL; n = 78) or placebo (n = 39). Angiomyolipoma
      response rates were analysed in patients (n = 44) with target baseline
      angiomyolipoma lesions (>=1 angiomyolipoma; longest diameter >=1.0 cm). An
      angiomyolipoma response rate, defined as the proportion of patients with
      confirmed angiomyolipoma response, was assessed by kidney CT or MRI screening at
      baseline, at 12, 24 and 48 weeks and annually. RESULTS: Angiomyolipoma response
      rates were 53.3% (16/30) and 0% (0/14) for everolimus- and placebo-treated
      patients, respectively. Angiomyolipoma reductions >=50% in the sum of volumes of
      all target lesions were seen only in everolimus-treated patients (56.5, 78.3 and
      80.0%) compared with placebo-treated patients (0% at each time point) at Weeks
      12, 24 and 48, respectively. Greater percentages of everolimus-treated patients
      had angiomyolipoma reductions >=30% at these same time points (82.6, 100 and 100%
      versus 8.3, 18.2 and 16.7% for everolimus versus placebo, respectively).
      CONCLUSIONS: Everolimus showed efficacy in reducing angiomyolipoma lesion volume
      in patients with SEGA associated with TSC.The trial is registered with
      ClinicalTrials.gov, number NCT00789828;
      http://clinicaltrials.gov/ct2/show/NCT00789828?term=EXIST-1&rank=1.

PMID- 24729043
TI  - A stationary wavelet transform based approach to registration of planning CT and
      setup cone beam-CT images in radiotherapy.
AB  - Image registration between planning CT images and cone beam-CT (CBCT) images is
      one of the key technologies of image guided radiotherapy (IGRT). Current image
      registration methods fall roughly into two categories: geometric features-based
      and image grayscale-based. Mutual information (MI) based registration, which
      belongs to the latter category, has been widely applied to multi-modal and mono
      modal image registration. However, the standard mutual information method only
      focuses on the image intensity information and overlooks spatial information,
      leading to the instability of intensity interpolation. Due to its use of
      positional information, wavelet transform has been applied to image registration
      recently. In this study, we proposed an approach to setup CT and cone beam-CT
      (CBCT) image registration in radiotherapy based on the combination of mutual
      information (MI) and stationary wavelet transform (SWT). Firstly, SWT was applied
      to generate gradient images and low frequency components produced in various
      levels of image decomposition were eliminated. Then inverse SWT was performed on
      the remaining frequency components. Lastly, the rigid registration of gradient
      images and original images was implemented using a weighting function with the
      normalized mutual information (NMI) being the similarity measure, which
      compensates for the lack of spatial information in mutual information based image
      registration. Our experiment results showed that the proposed method was highly
      accurate and robust, and indicated a significant clinical potential in improving
      the accuracy of target localization in image guided radiotherapy (IGRT).

PMID- 24729044
TI  - Selenium-enriched exopolysaccharides improve skeletal muscle glucose uptake of
      diabetic KKAy mice via AMPK pathway.
AB  - Selenium-enriched exopolysaccharides (EPS) produced by Enterobacter cloacae Z0206
      have been proven to possess effect on reducing blood glucose level in diabetic
      mice. To investigate the specific mechanism, we studied the effects of oral
      supply with EPS on skeletal muscle glucose transportation and consumption in high
      fat-diet-induced diabetic KKAy mice. We found that EPS supplementation increased
      expressions of glucose transporter 4 (Glut4), hexokinase 2 (hk2), phosphorylation
      of AMP-activated kinase subunit alpha2 (pAMPKalpha2), and peroxisome proliferator
      activated receptor gamma coactivator 1alpha (PGC-1alpha), and increased
      expression of characteristic protein of oxidative fibers such as troponin I and
      cytochrome c (Cytc). Furthermore, we found that EPS increased glucose uptake and
      expressions of pAMPKalpha2 and PGC-1alpha in palmitic acid (PA)-induced C2C12
      cells. However, while EPS inhibited AMPKalpha2 with interference RNA (iRNA),
      effects of EPS on the improvement of glucose uptake diminished. These results
      indicated that EPS may improve skeletal muscle glucose uptake of diabetic KKAy
      mice through AMPKalpha2-PGC-1alpha pathway. 

PMID- 24729045
TI  - Pica and rumination behavior among individuals seeking treatment for eating
      disorders or obesity.
AB  - OBJECTIVE: Pica and rumination disorder (RD)-formerly classified within DSM-IV
      Feeding and Eating Disorders of Infancy or Early Childhood-are now classified
      within DSM-5 Feeding and Eating Disorders. Though pica and RD have been studied
      in select populations (e.g., pregnant women, intellectually disabled persons),
      their typical features and overall prevalence remain unknown. This study examined
      the clinical characteristics and frequency of DSM-5 pica and RD among individuals
      seeking treatment for eating disorders and obesity. METHOD: We conducted
      structured interviews with adolescent and young adult females from a residential
      eating disorder center (N = 149), and adult males and females with overweight or
      obesity from an outpatient weight-loss clinic (N = 100). RESULTS: Several
      participants reported ingesting non-nutritive substances (e.g., ice) for weight
      control purposes. However, only 1.3% (n = 2; 95% CI: .06% to 5.1%) at the
      residential eating disorder center and 0% at the weight-loss clinic met DSM-5
      criteria for pica, consuming gum and plastic. Although no eating disorder
      participants were eligible for an RD diagnosis due to DSM-5 trumping rules, 7.4%
      (n = 11; 95% CI: 4.0% to 12.9%) endorsed rumination behavior under varying
      degrees of volitional control. At the weight-loss clinic, 2.0% (n = 2; 95% CI:
      0.1% to 7.4%) had RD. DISCUSSION: DSM-5 pica and RD were rare in our sample of
      individuals seeking treatment for eating disorders and obesity, but related
      behaviors were more common. The wide range of pica and rumination presentations
      highlights the challenges of differential diagnosis with other forms of
      disordered eating.

PMID- 24729049
TI  - Occurrence and distribution of organophosphate flame retardants/plasticizers in
      wastewater treatment plant sludges from the Pearl River Delta, China.
AB  - Organophosphate esters (OPs) are widely used as flame retardants or plasticizers
      and are ubiquitously distributed in the environment. In the present study, the
      occurrence and distribution of 7 widely used OPs were analyzed in sludge samples
      collected from 19 municipal wastewater treatment plants in the Pearl River Delta,
      South China. All analytes were detected in these samples, and the total
      concentration of OPs ranged from 96.7 ug/kg to 1312.9 ug/kg dry weight, with a
      mean value of 420.1 ug/kg dry weight. In most sludge samples OPs exhibited a
      similar distribution pattern, for example, tris(2-butoxyethyl) phosphate (TBEP)
      and triphenyl phosphate (TPhP) were identified as the dominant compounds.
      However, the results also indicated significantly higher levels of OPs in
      specific sludges, such as tri-n-butyl phosphate (804.9 ug/kg), TBEP (783.7
      ug/kg), TPhP (656.7 ug/kg), and tritolyl phosphate (265.0 ug/kg), which implied
      different discharge sources in the studied areas.

PMID- 24729046
TI  - Effects of laser irradiation (670-nm InGaP and 830-nm GaAlAs) on burn of second
      degree in rats.
AB  - This study investigated the effects of 670-nm indium gallium phosphide (InGaP)
      and 830-nm gallium aluminum arsenide (GaAlAs) laser therapy on second-degree
      burns induced on the back of Wistar rats. Sixty-three male Wistar rats were
      anesthetized, and second-degree burns were made on their back. The animals were
      then divided randomly into three groups: control (C), animals treated with 670-nm
      InGaP laser (LIn), and animals treated with 830-nm GaAlAs laser (LGa). The wound
      areas were removed after 2, 6, 10, 14, and 18 days of treatment and submitted to
      structural and morphometric analysis. The following parameters were studied:
      total number of granulocytes and fibroblasts, number of newly formed blood
      vessels, and percentage of birefringent collagen fibers in the repair area.
      Morphometric analysis showed that different lasers 670-nm InGaP and 830-nm GaAlAs
      reduced the number of granulocytes and an increase of newly formed vessels in
      radiated lesions. The 670-nm InGaP laser therapy was more effective in increasing
      the number of fibroblasts. The different treatments modified the expression of
      VEGF and TGF-beta1, when compared with lesions not irradiated. The different
      types of light sources showed similar effects, improved the healing of second
      degree burns and can help for treating this type of injury. Despite the large
      number of studies with LLTI application in second-degree burns, there is still
      divergence about the best irradiation parameters to be used. Further studies are
      needed for developing a protocol effective in treating this type of injury.

PMID- 24729050
TI  - The EQ-5D: a new tool for studying clinical outcomes in chronic rhinosinusitis.
AB  - OBJECTIVES/HYPOTHESIS: To describe the role and applicability of the EuroQol 5
      Dimension, 5-Level (EQ-5D-5L) questionnaire for the assessment of general health
      related quality of life in patients with chronic rhinosinusitis. STUDY DESIGN:
      Prospective cohort study. METHODS: The EQ-5D-5L was administered to 462 patients
      with refractory chronic rhinosinusitis before and 3 months after sinus surgery.
      Preoperative and postoperative scores across each of five health dimensions were
      analyzed and the results compared to those obtained from two widely used chronic
      rhinosinusitis outcomes instruments: the Chronic Sinusitis Survey (CSS) and
      SinoNasal Outcomes Test-22 (SNOT-22). RESULTS: Three hundred and fifty patients
      completed the five questions and visual analog scale (VAS) of the EQ-5D at
      baseline and at 3 months for a response rate of 75.8%. There were no incomplete
      questionnaires. The frequency of patients reporting problems in the EQ-5D domains
      of pain/discomfort, anxiety/depression, and usual activities decreased following
      sinus surgery (74.3% vs. 34.4%, 48.6% vs. 31.4%, and 30.6% vs. 19.4%,
      respectively; all P < 0.001). The domains of mobility and self-care did not
      demonstrate statistically significant change. EQ-5D VAS (standard deviation)
      improved from 73.4 (16.9) before surgery to 82.0 (14.4) after surgery (P <
      0.001). Preoperative VAS correlated with SNOT-22 scores (Pearson coefficient of
      0.50; P < 0.01). Postoperative change in VAS and SNOT-22 scores demonstrated
      moderate correlation (Pearson coefficient of 0.36, P < 0.01). CONCLUSION: The EQ
      5D is a general health measure with sensitivity to clinical change in
      rhinosinusitis that support its use for monitoring patient outcomes. The limited
      response burden and ability to directly calculate health utility make it an
      attractive tool for rhinosinusitis outcomes research.

PMID- 24729052
TI  - Dust from Zambian smelters: mineralogy and contaminant bioaccessibility.
AB  - Metal smelting is often responsible for local contamination of environmental
      compartments. Dust materials escaping from the smelting facilities not only
      settle in the soil, but can also have direct effects on populations living close
      to these operations (by ingestion or inhalation). In this particular study, we
      investigate dusts from Cu-Co metal smelters in the Zambian Copperbelt, using a
      combination of mineralogical techniques (XRD, SEM/EDS, and TEM/EDS), in order to
      understand the solid speciation of the contaminants, as well as their
      bioaccessibility using in vitro tests in simulated gastric and lung fluids to
      assess the exposure risk for humans. The leaching of metals was mainly dependent
      on the contaminant mineralogy. Based on our results, a potential risk can be
      recognized, particularly from ingestion of the dust, with bioaccessible fractions
      ranging from 21 to 89% of the total contaminant concentrations. In contrast,
      relatively low bioaccessible fractions were observed for simulated lung fluid
      extracts, with values ranging from 0.01% (Pb) up to 16.5% (Co) of total
      contaminant concentrations. Daily intakes via oral exposure, calculated for an
      adult (70 kg, ingestion rate 50 mg dust per day), slightly exceeded the tolerable
      daily intake limits for Co (1.66* for fly ash and 1.19* for slag dust) and
      occasionally also for Pb (1.49*, fly ash) and As (1.64*, electrostatic
      precipitator dust). Cobalt has been suggested as the most important pollutant,
      and the direct pathways of the population's exposures to dust particles in the
      industrial parts of the Zambian Copperbelt should be further studied in
      interdisciplinary investigations.

PMID- 24729051
TI  - Foliar uptake and metal(loid) bioaccessibility in vegetables exposed to
      particulate matter.
AB  - At the global scale, high concentrations of particulate matter (PM) enriched with
      metal(loid)s are currently observed in the atmosphere of urban areas. Foliar lead
      uptake was demonstrated for vegetables exposed to airborne PM. Our main objective
      here was to highlight the health risk associated with the consumption of
      vegetables exposed to foliar deposits of PM enriched with the various
      metal(loid)s frequently observed in the atmosphere of urban areas (Cd, Sb, Zn and
      Pb). Leaves of mature cabbage and spinach were exposed to manufactured mono
      metallic oxide particles (CdO, Sb2O3 and ZnO) or to complex process PM mainly
      enriched with lead. Total and bioaccessible metal(loid) concentrations were then
      measured for polluted vegetables and the various PM used as sources. Finally,
      scanning electronic microscopy coupled with energy dispersive X-ray microanalysis
      was used to study PM-phyllosphere interactions. High quantities of Cd, Sb, Zn and
      Pb were taken up by the plant leaves. These levels depended on both the plant
      species and nature of the PM, highlighting the interest of acquiring data for
      different plants and sources of exposure in order to better identify and manage
      health risks. A maximum of 2% of the leaf surfaces were covered with the PM.
      However, particles appeared to be enriched in stomatal openings, with up to 12%
      of their area occupied. Metal(loid) bioaccessibility was significantly higher for
      vegetables compared to PM sources, certainly due to chemical speciation changes.
      Taken together, these results confirm the importance of taking atmospheric PM
      into account when assessing the health risks associated with ingestion of
      vegetables grown in urban vegetable crops or kitchen gardens.

PMID- 24729053
TI  - Health risk estimates for groundwater and soil contamination in the Slovak
      Republic: a convenient tool for identification and mapping of risk areas.
AB  - We undertook a quantitative estimation of health risks to residents living in the
      Slovak Republic and exposed to contaminated groundwater (ingestion by adult
      population) and/or soils (ingestion by adult and child population). Potential
      risk areas were mapped to give a visual presentation at basic administrative
      units of the country (municipalities, districts, regions) for easy discussion
      with policy and decision-makers. The health risk estimates were calculated by US
      EPA methods, applying threshold values for chronic risk and non-threshold values
      for cancer risk. The potential health risk was evaluated for As, Ba, Cd, Cu, F,
      Hg, Mn, NO3 (-), Pb, Sb, Se and Zn for groundwater and As, B, Ba, Be, Cd, Cu, F,
      Hg, Mn, Mo, Ni, Pb, Sb, Se and Zn for soils. An increased health risk was
      identified mainly in historical mining areas highly contaminated by geogenic
      anthropogenic sources (ore deposit occurrence, mining, metallurgy). Arsenic and
      antimony were the most significant elements in relation to health risks from
      groundwater and soil contamination in the Slovak Republic contributing a
      significant part of total chronic risk levels. Health risk estimation for soil
      contamination has highlighted the significance of exposure through soil ingestion
      in children. Increased cancer risks from groundwater and soil contamination by
      arsenic were noted in several municipalities and districts throughout the country
      in areas with significantly high arsenic levels in the environment. This approach
      to health risk estimations and visualization represents a fast, clear and
      convenient tool for delineation of risk areas at national and local levels. 

PMID- 24729054
TI  - Assessing quality of life in young adult cancer survivors: development of the
      Survivorship-Related Quality of Life scale.
AB  - PURPOSE: Scientific advances in treatments and outcomes for those diagnosed with
      cancer in late adolescence and early adulthood depend, in part, on the
      availability of adequate assessment tools to measure health-related quality of
      life (HRQOL) for survivors in this age group. Domains especially relevant to late
      adolescence and young adulthood (LAYA; e.g., education and career, committed
      romantic relationships, worldview formation) are typically overlooked in studies
      assessing the impact of cancer, usually more appropriate for middle-aged or older
      survivors. Current HRQOL measures also tend to assess issues that are salient
      during or shortly after treatment rather than reflecting life years after
      treatment. METHODS: To develop a new measure to better capture the experience of
      LAYA cancer survivors in longer-term survivorship (the LAYA Survivorship-Related
      Quality of Life measure, LAYA-SRQL), we completed an extensive measure
      development process. After a literature review and focus groups with LAYA cancer
      survivors, we generated items and ran confirmatory factor and reliability
      analyses using a sample of 292 LAYA cancer survivors. We then examined validity
      using existing measures of physical and mental health, quality of life, and
      impact of cancer. RESULTS: The final model consisted of two domains (satisfaction
      and impact), each consisting of ten factors: existential/spirituality, coping,
      relationship, dependence, vitality, health care, education/career, fertility,
      intimacy/sexuality, and cognition/memory. Confirmatory factor analysis and
      validity analyses indicated that the LAYA-SRQL is a psychometrically sound
      instrument with good validity. CONCLUSION: The LAYA-SRQL fills an important need
      in survivorship research, providing a way to assess HRQOL in LAYAs in a
      developmentally informed way.

PMID- 24729055
TI  - Conceptualizing global health-related quality of life in bladder cancer.
AB  - PURPOSE: Patients' values for health outcomes are central to treatment decisions
      in bladder cancer (BCa). An instrument incorporating the expressed preferences of
      BCa patients, as measured by utility, can inform clinical guidelines, resource
      allocation and policy decisions. Developing this instrument requires a formal
      conceptual framework summarizing the important domains comprising global health
      related quality of life (HRQOL) in BCa. METHODS: We performed a systematic
      literature search on the HRQOL effects of BCa and its treatments to generate
      initial items in Medline, Embase, CINAHL and PsychInfo up to January 2013.
      Thematic synthesis was used to group related items into overarching themes
      (domains) and create a provisional conceptual framework. In focus groups, 12 BCa
      experts and 47 BCa patients with diverse clinical histories generated further
      items to inform the final conceptual framework. RESULTS: We retrieved 1,275
      citations and reviewed 170 full-text publications. One hundred and sixty-nine
      items were extracted into 12 domains. Study investigators used the findings from
      the focus groups to confirm the domains and condense the list to 83 clinically
      important items. Functional limitations in work, travel, social interaction and
      sleep lowered HRQOL in many domains. The final conceptual framework included BCa
      specific (urinary, sexual, bowel, body image) and generic domains (pain, vigor,
      social, psychological, sleep, functional, family relationship, medical care
      relationship). CONCLUSIONS: A conceptual framework including 12 domains can serve
      as the foundation for the development of an instruments measuring global HRQOL in
      BCa and in particular, one that can measure patient preferences and generate
      utilities.

PMID- 24729056
TI  - Longitudinal changes in health-related quality of life in normal glucose
      tolerance, prediabetes and type 2 diabetes: results from the KORA S4/F4 cohort
      study.
AB  - PURPOSE: The aim of this study was to examine how transition between normal
      glucose tolerance, prediabetes and diabetes over a 7 year period is associated
      with change in health-related quality of life (HRQL) in an elder German
      population-based cohort. METHODS: We used data from 1,046 participants of the
      KORA S4/F4 cohort study aged 55-74 years at baseline. Based on an oral glucose
      tolerance test, prediabetes was defined as impaired fasting glucose and/or
      impaired glucose tolerance. HRQL was assessed with the SF-12 questionnaire. Using
      linear regression, we estimated mean change in HRQL over time, depending on
      glucose status at baseline and follow-up, adjusted by demographic and lifestyle
      variables. RESULTS: Individuals progressing to prediabetes or diabetes
      experienced a greater loss in the physical component score than patients with
      persistent normal glucose tolerance (-2.31 and -7.44 vs. -1.08), but the
      difference was only significant for subjects converting to diabetes. Subjects
      with prediabetes at baseline and diabetes at follow-up had a significant loss in
      mental health compared to subjects with persistent prediabetes. CONCLUSIONS:
      There is first evidence that worsening of glucose metabolism over time is
      associated with deteriorating HRQL, however, further and larger longitudinal
      studies are needed to confirm these findings.

PMID- 24729060
TI  - Active digital microfluidic paper chips with inkjet-printed patterned electrodes.
AB  - Active, paper-based, microfluidic chips driven by electrowetting are fabricated
      and demonstrated for reagent transport and mixing. Instead of using the passive
      capillary force on the pulp to actuate a flow of a liquid, a group of digital
      drops are transported along programmed trajectories above the electrodes printed
      on low-cost paper, which should allow point-of-care production and diagnostic
      activities in the future. 

PMID- 24729065
TI  - Homicide or suicide? Xylophagia: a possible explanation for extraordinary autopsy
      findings.
AB  - Determining the cause of death and differentiating self-inflicted injuries from
      non-self-inflicted injuries is a primary goal in legal medicine. Especially with
      unidentified decedents, autopsy findings alone are often not sufficient; there is
      no knowledge of pre-existing conditions and only circumstantial evidence is
      available from the scene of death. In our case, radiological, histological, and
      toxicological examinations provided an explanatory model for extraordinary
      autopsy findings consistent with pica, a rare eating disorder. In cases of pica,
      variable and potentially lethal complications emerge, depending on the type and
      amount of material ingested. Our case is of an apparently uncontrolled intake of
      wooden objects (xylophagia). The resulting mechanical damage to the
      gastrointestinal tract and subsequent soft tissue damage supports that this
      behavioral disorder is not only of medical concern, but also identifies it as a
      mental disease with medico-legal relevance. 

PMID- 24729066
TI  - What is the standard regimen for patients with acute promyelocytic leukemia?
AB  - Modern guidelines based on a large international consensus indicate that
      treatment of newly diagnosed acute promyelocytic leukemia (APL) requires
      distinguishing at presentation low-intermediate (<10 * 10(9)/L WBC) from high
      risk (>10 * 10(9)/L WBC) disease. The concomitant use of all-trans retinoic acid
      (ATRA) and anthracycline based chemotherapy, with inclusion of AraC in
      consolidation for hyperleucocytic patients, has remained the standard of care for
      the past two decades. The advent of arsenic trioxide (ATO) and results from a
      large randomized trial, have recently challenged the standard ATRA-chemotherapy
      approach suggesting that at least patients in the low-intermediate category may
      be cured without chemotherapy using the ATRA-ATO combination. 

PMID- 24729067
TI  - Effect of granular activated carbon concentration on the content of organic
      matter and salt, influencing E. coli activity and survival in fluidized bed
      disinfection reactor.
AB  - Granular activated carbon (GAC) is used in water treatment systems, typically to
      remove pollutants such as natural organic matter, volatile organic compounds,
      chlorine, taste, and odor. GAC is also used as a key component of a new
      technology that combines a fluidized bed reactor with radio frequency electric
      fields for disinfection. So far, the effects of GAC on bacteria in these
      fluidized bed reactors are unclear. This paper describes a systematic study of
      the physico-chemical changes in five microbial media compositions caused by
      different concentrations (23-350 g/L) of GAC, and the effects of these physico
      chemical changes on the metabolic activity and survival of a model microorganism
      (Escherichia coli YMc10) in a fluidized bed reactor. The chemical adsorption
      taking place in suspensions with specific GAC changed nutritional, osmotic, and
      pH conditions in the investigated microbial media (LB, diluted LB, PBS, diluted
      PBS, and tap water), leading to a decay of the metabolic activity and survival of
      E. coli. Especially media that are poor in organic and mineral compounds (e.g.,
      PBS) with suspended GAC showed a concentration decay of 3.5 Log CFU/mL E. coli
      after 6 h. Organic compounds depletion and severe pH variation were enhanced in
      the presence of higher GAC concentrations.

PMID- 24729068
TI  - The effect of driven exercise on treatment outcomes for adolescents with anorexia
      and bulimia nervosa.
AB  - OBJECTIVE: This study investigated the prevalence of driven exercise (DE) and its
      role in treatment outcome for adolescents with bulimia nervosa (BN) and anorexia
      nervosa (AN). METHOD: Participants were 201 adolescents with an eating disorder
      (ED) (80 with BN and 121 with AN) presenting for outpatient treatment at two
      specialist clinics. All adolescents participated in one of two randomized
      controlled trials. Descriptive statistics were conducted to evaluate the presence
      and frequency of baseline DE. Exploratory hierarchical regressions were used to
      evaluate the effect of baseline DE on treatment outcomes. RESULTS: About 66.3% of
      adolescents with BN and 23.1% of adolescents with AN presented with baseline DE.
      The presence of baseline DE predicted significantly worse outcomes for
      adolescents with AN in terms of ED symptom severity (ps < .004); however,
      baseline DE did not significantly predict any of the evaluated outcomes for
      adolescents with BN (ps < .05). DISCUSSION: The results of this secondary
      exploratory data suggest that DE is prevalent for adolescents with BN and AN.
      However, DE may be related to different constructs for adolescents with AN than
      those with BN, suggesting differences in treatment needs.

PMID- 24729070
TI  - Heat shock protein peptide complex-96 (HSPPC-96) vaccination for recurrent
      glioblastoma: a phase II, single arm trial.

PMID- 24729069
TI  - Immune response induced by candidate Sarcoptes scabiei var. cuniculi DNA vaccine
      encoding paramyosin in mice.
AB  - Sarcoptes scabiei is the causal agent of the highly contagious disease sarcoptic
      mange (scabies) that affects animals and humans worldwide. An increasing number
      of cases of treatment failure is being reported because of drug resistance. The
      development of a specific vaccine would be a sustainable option for control of
      this disease. In this study, we cloned and expressed a S. scabiei gene encoding
      paramyosin (PAR) and investigated the immune response elicited by DNA encoding
      PAR in mice. The ability of the DNA vaccine to express antigen in COS-7 cells was
      confirmed by RT-PCR and IFA. The immune response induced by DNA vaccine was
      investigated by ELISA, splenocyte proliferation assay, and cytokine production
      assay. Compared to the pVAX1 control group, the PAR DNA vaccination group showed
      the higher levels of IgG, IgG1, IgG2a, IgE, IgM, stronger lymphocyte
      proliferation in mouse spleen, and larger production of IL-2, IL-4, IL-5, and IFN
      gamma in the supernatant of cultures from splenocytes. These results indicated
      that the PAR DNA vaccine induced a mixed Th1/Th2 response in mice. In conclusion,
      our results revealed that the S. scabiei PAR DNA vaccine induced both a humoral
      and cellular immune response, which would provide basic data for the further
      study to develop an effective vaccine against sarcoptic mange.

PMID- 24729071
TI  - Eastern Caribbean Physicians' Responses to Providing HIV/AIDS Care in Resource
      Limited Settings: We've Come a Long Way, but We're Not There Yet.
AB  - Physicians' ability to provide care to patients living with HIV/AIDS (PLWHA) in
      the Eastern Caribbean is influenced by economic constraints, sociocultural norms
      that govern interpersonal interactions, and the pervasive stigma linked to the
      disease. Although the economic environment determines national capacity to
      acquire various treatment and monitoring technologies, Eastern Caribbean
      physicians respond to practicing in a resource-limited setting by making choices
      that are influenced by the collectivist ethos that governs interpersonal
      relationships. Through qualitative interviews, the study finds that the social
      stigma associated with the disease requires physicians to "go the extra mile" to
      provide care in ways that allow PLWHA to protect their privacy in small, closely
      networked societies.

PMID- 24729072
TI  - Patient Access to Online Visit Notes: Perceptions of Doctors and Patients at an
      Urban HIV/AIDS Clinic.
AB  - Patients living with HIV/AIDS face large societal and medical challenges.
      Inviting patients to read their doctors' visit notes via secure electronic
      portals may empower patients and improve health. We investigated whether
      utilization and perceptions about access to doctors' notes differed among doctors
      and patients in an HIV/AIDS clinic versus primary care setting. We analyzed pre-
      and 1-year postintervention data from 99 doctors and 3819 patients. HIV clinic
      patients did not report differences in perceived risks and benefits compared to
      primary care clinic patients, however, they were more likely to share notes with
      friends (33% versus 9%, P=.002), other health professionals (24% versus 8%,
      P=.03), or another doctor (38% versus 9%, P<.0001). HIV clinic doctors were less
      likely than primary care doctors to change the level of candor in visit notes
      (P<.04). Our findings suggest that HIV clinic patients and doctors are ready to
      share visit notes online.

PMID- 24729074
TI  - Computed tomography utilization rates after the placement of a scanner in an
      emergency department: a single-center experience.
AB  - The convenience of a computed tomography (CT) scanner in the emergency department
      (ED) may impact utilization rates. Our primary aim was to determine the rate of
      utilization before and after the placement of an ED CT scanner. Secondary aims
      were to determine the rate of utilization by anatomic region and during a 5-month
      period when the ED scanner was unavailable. We performed an electronic chart
      review of our ED with an annual census of 70,000 patients. We identified all
      patients over the age of 21 who had a CT scan performed from January 2008 to
      October 2010. Predetermined data elements were extracted by trained, hypothesis
      blinded abstractors. Comparisons overall and within scan subtype were performed
      using seasonal matching. We found a CT utilization rate of 114 per 1,000 patient
      visits before and 139 per 1,000 patient visits after the placement of a CT
      scanner in the ED (p<0.0001). Linear regression analysis found a line with a
      slope of beta=0.114 (95 % CI=0.107-0.121) and an R2 of 0.508. CT rates increased
      in the following regions: head CTs by 14 per 1,000 visits (p<0.0001); neck CTs by
      3 per 1,000 visits (p<0.0001); abdomen/pelvis CTs by 4 per 1,000 visits
      (p=0.0015); "other" CTs by 2 per 1,000 visits (p<0.0001). Increased rates of
      chest and facial CTs approached significance with p values of 0.05. During the 5
      month downtime, utilization remained unchanged at 141 per 1,000 visits (p=0.38).
      Overall CT utilization increased after the placement of a scanner in the ED. Most
      subtypes of scan increased. Utilization was unchanged during a period of ED
      scanner unavailability, suggesting that increased utilization may be difficult to
      reverse.

PMID- 24729075
TI  - Arsenic partitioning among particle-size fractions of mine wastes and stream
      sediments from cinnabar mining districts.
AB  - Tailings from abandoned mercury mines represent an important pollution source by
      metals and metalloids. Mercury mining in Asturias (north-western Spain) has been
      carried out since Roman times until the 1970s. Specific and non-specific arsenic
      minerals are present in the paragenesis of the Hg ore deposit. As a result of
      intensive mining operations, waste materials contain high concentrations of As,
      which can be geochemically dispersed throughout surrounding areas. Arsenic
      accumulation, mobility and availability in soils and sediments are strongly
      affected by the association of As with solid phases and granular size
      composition. The objective of this study was to examine phase associations of As
      in the fine grain size subsamples of mine wastes (La Soterrana mine site) and
      stream sediments heavily affected by acid mine drainage (Los Rueldos mine site).
      An arsenic-selective sequential procedure, which categorizes As content into
      seven phase associations, was applied. In spite of a higher As accumulation in
      the finest particle-size subsamples, As fractionation did not seem to depend on
      grain size since similar distribution profiles were obtained for the studied
      granulometric fractions. The presence of As was relatively low in the most mobile
      forms in both sites. As was predominantly linked to short-range ordered Fe
      oxyhydroxides, coprecipitated with Fe and partially with Al oxyhydroxides and
      associated with structural material in mine waste samples. As incorporated into
      short-range ordered Fe oxyhydroxides was the predominant fraction at sediment
      samples, representing more than 80% of total As.

PMID- 24729076
TI  - Relative bioavailability of soil-bound chlordecone in growing lambs.
AB  - The pollution of soil with the pesticide chlordecone (CLD) is a problem for the
      use of agricultural surfaces even years after its use has been forbidden.
      Therefore, the exposure of free-ranged animals such as ruminants needs to be
      investigated in order to assess the risk of contamination of the food chain.
      Indeed, measured concentrations could be integrated in a lowered extent if the
      soil binding would reduce the bioavailability of the pesticide. This
      bioavailability of soil-bound CLD in a heavily polluted andosol has been
      investigated relatively of CLD given via spiked oil. Twenty-four weaned lambs
      were exposed to graded doses of 2, 4 or 6 MUg CLD/kg body weight during 15 days
      via the contaminated soil in comparison to spiked oil. The concentration of this
      pesticide has been determined in two target tissues: blood serum and kidney fat.
      The relative bioavailability (RBA) corresponds to the slope ratio between the
      test matrix-contaminated soil- in comparison to the reference matrix oil. The RBA
      of the soil-bound CLD was not found to significantly differ from the reference
      matrix oil in lambs meaning that the pesticide ingested by grazing ruminants
      would not be sequestered by soil binding. Therefore, CLD from soil gets
      bioavailable within the intestinal level and exposure to contaminated soil has to
      be integrated in risk assessments.

PMID- 24729073
TI  - Diversity of the metal-transporting P1B-type ATPases.
AB  - The P1B-ATPases are integral membrane proteins that couple ATP hydrolysis to
      metal cation transport. Widely distributed across all domains of life, these
      enzymes have been previously shown to transport copper, zinc, cobalt, and other
      thiophilic heavy metals. Recent data suggest that these enzymes may also be
      involved in nickel and/or iron transport. Here we have exploited large amounts of
      genomic data to examine and classify the various P1B-ATPase subfamilies.
      Specifically, we have combined new methods of data partitioning and network
      visualization known as Transitivity Clustering and Protein Similarity Networks
      with existing biochemical data to examine properties such as length, speciation,
      and metal-binding motifs of the P1B-ATPase subfamily sequences. These data reveal
      interesting relationships among the enzyme sequences of previously established
      subfamilies, indicate the presence of two new subfamilies, and suggest the
      existence of new regulatory elements in certain subfamilies. Taken together,
      these findings underscore the importance of P1B-ATPases in homeostasis of nearly
      every biologically relevant transition metal and provide an updated framework for
      future studies.

PMID- 24729077
TI  - Platinum in PM2.5 of the metropolitan area of Mexico City.
AB  - The increase in platinum (Pt) in the airborne particulate matter with size <=2.5
      um (PM2.5) in urban environments may be interpreted as result of the abrasion and
      deterioration of automobile catalyst. Nowadays, about four million vehicles in
      Mexico City use catalytic converters, which means that their impact should be
      considered. In order to evaluate the contribution of Pt to environmental
      pollution of the metropolitan area of Mexico City (MAMC), airborne PM2.5 was
      collected at five different sites in the urban area (NW, NE, C, SW, SE) in 2011
      during April (dry-warm season), August (rainy season) and December (dry-cold
      season). Analytical determinations were carried out using a ICP-MS with a
      collision cell and kinetic energy discrimination. The analytical and instrument
      performance was evaluated with standard road dust reference material (BCR-723).
      Median Pt concentration in the analyzed particulate was is 38.4 pg m(-3) (minimal
      value 1 pg m(-3) maximal value 79 pg m(-3)). Obtained Pt concentrations are
      higher than those reported for other urban areas. Spatial variation shows that SW
      had Pt concentration significantly higher than NW and C only. Seasonal variation
      shows that Pt median was higher in rainy season than in both dry seasons. A
      comparison of these results with previously reported data of PM10 from 1991 and
      2003 in the same studied area shows a worrying increase in the concentration of
      Pt in the air environment of MAMC. 

PMID- 24729078
TI  - Topical antibiotics for the management of bacterial keratitis: an evidence-based
      review of high quality randomised controlled trials.
AB  - BACKGROUND: Severe bacterial keratitis (BK) typically requires intensive
      antimicrobial therapy. Empiric therapy is usually with a topical fluoroquinolone
      or fortified aminoglycoside-cephalosporin combination. Trials to date have not
      reached any consensus as to which antibiotic regimen most effectively treats BK.
      METHODS: A systematic review and meta-analysis using Cochrane methodology was
      undertaken to evaluate the effectiveness of topical antibiotics in the management
      of BK. Outcomes included treatment success, time to cure, serious complications
      of infection and adverse effects. RESULTS: A comprehensive search for trials
      resulted in 27 956 abstracts for review. This eventually resulted in 16 high
      quality trials involving 1823 participants included in the review. Treatment
      success, time to cure and serious complications of infection were comparable
      among all antibiotic treatments included in the review. Furthermore, there was no
      evidence of difference in the risk of corneal perforation with any included
      antibiotics or antibiotic classes. Fluoroquinolones significantly reduced risk of
      ocular discomfort and chemical conjunctivitis but increased the risk of white
      precipitate formation compared with aminoglycoside-cephalosporin. Fortified
      tobramycin-cefazolin was approximately three times more likely to cause ocular
      discomfort than other topical antibiotics. CONCLUSIONS: Results of this review
      suggest no evidence of difference in comparative effectiveness between
      fluoroquinolones and aminoglycoside-cephalosporin treatment options in the
      management of BK. There were differences in safety profile, however.
      Fluoroquinolones decreased the risk of ocular discomfort and chemical
      conjunctivitis while ciprofloxacin increased the risk of white corneal
      precipitate compared with aminoglycoside-cephalosporin.

PMID- 24729079
TI  - Retinal vascular oximetry during ranibizumab treatment of central retinal vein
      occlusion.
AB  - PURPOSE: To investigate the effect of intravitreal injections of the vascular
      endothelial growth factor inhibitor ranibizumab on retinal oxygenation in
      patients with central retinal vein occlusion (CRVO). METHODS: Retinal oxygen
      saturation in patients with CRVO was analysed using the Oxymap Retinal Oximeter
      P3, before and during 6 months of treatment with intravitreal injections of
      ranibizumab. RESULTS: At presentation, retinal venous oxygen saturation was lower
      in eyes with CRVO than in the healthy fellow eyes (32+/-13% vs 59+/-10%,
      respectively, p=0.001) whereas retinal arterial saturation was higher in eyes
      with CRVO than in the fellow eyes (95%+/-8% and 91%+/-3%, p=0.04). Mean visual
      acuity increased from 51+/-24 letters ETDRS at baseline to 66+/-24 and 69+/-20
      letters ETRDS, respectively, at 3 months and 6 months treatment (mean+/-SD,
      p<0.0001, repeated measures analysis of variance) and central retinal thickness
      was reduced from 697+/-139 um to 368+/-113 um and 340+/-96 um, respectively, from
      baseline to 3 months and 6 months treatment (p<0.0001). Venous saturation
      increased during treatment (from 35.5%+/-13.8% at baseline to 43.1%+/-10.8% and
      43.5%+/-13.7% after 3 months and 6 months treatment, respectively, p=0.012),
      while no significant change was found in arterial saturation (p=0.24).
      CONCLUSIONS: Retinal venous oxygen saturation was markedly reduced in untreated
      CRVO and was roughly halfway normalised during intravitreal ranibizumab
      treatment. Retinal artery oxygen saturation was not reduced in CRVO. TRIAL
      REGISTRATION NUMBER: NCT01360385.

PMID- 24729083
TI  - Ecological factors contributing to variability of persistent organic pollutant
      bioaccumulation within forage fish communities of the Detroit River, Ontario,
      Canada.
AB  - Understanding variability of contaminant bioaccumulation within and among fish
      populations is critical for distinguishing between the chemical and biological
      mechanisms that contribute to food web biomagnification and quantifying
      contaminant exposure risks in aquatic ecosystems. The present study examined the
      relative contributions of chemical hydrophobicity (octanol-water partition
      coefficient [KOW ]) and habitat use as factors regulating variability in
      polychlorinated biphenyl (PCB) congener bioaccumulation in 3 lower trophic level
      cyprinid species across spatial and temporal scales. Bluntnose minnows
      (Pimephales notatus), spottail shiners (Notropis hudsonius), and emerald shiners
      (Notropis atherinoides) were sampled at 3 locations in the Detroit River,
      Ontario, Canada. Variability in PCB concentration was evaluated with respect to
      several factors, including chemical hydrophobicity, site, season, species, and
      weight using sum of squares and Levene's test of homogeneity of variance.
      Individual variability in bioaccumulated congener-specific residues depended on
      chemical hydrophobicity with mid- and high-range KOW congeners (log KOW  >6.0),
      demonstrating the highest amount of variance compared with low KOW congeners.
      Different feeding strategies also contributed to the variance observed for mid
      range KOW congeners among species. In the present study, benthic feeding
      specialists exhibited lower variance in PCB concentrations compared with the 2
      generalist species. The results indicate that chemical hydrophobicity and feeding
      ecology not only contribute to differences in the biomagnification potentials of
      fish, but also regulate between-individual variation in PCB concentrations both
      across and within fish species.

PMID- 24729084
TI  - Analyzing 395,793 samples shows significant association between rs999737
      polymorphism and breast cancer.
AB  - Large-scale genome-wide association studies (GWAS) have been conducted and
      reported the association between rs999737 polymorphism at 14q24.1 (RAD51L1) and
      breast cancer risk. Following studies investigated rs999737 polymorphism in
      European and Asian populations. However, some of these studies reported weak and
      no significant association. Here, we reevaluated this association using large
      scale samples from previous 11 studies (n=395,793; 162,261 cases and 233,532
      controls) from the PubMed database. We evaluated the genetic heterogeneity among
      the selected studies. The pooled odds ratio (OR) is calculated by the fixed
      effect model. All statistical tests for heterogeneity and meta-analysis were
      computed using R package. We did not identify significant heterogeneity among the
      included studies using the allele model (P=0.1314 and I (2)=33.4 %). We observed
      significant association between rs999737 and breast cancer using the allele model
      (P=2.47E - 35, OR=0.92, 95 % confidence interval (CI) 0.91-0.93). Our analysis
      further supports previous findings that the rs999737 polymorphism contributes to
      breast cancer susceptibility. We believe that our finding will be very useful for
      future genetic studies in breast cancer.

PMID- 24729085
TI  - In memory of Garry Abelev 1928-2013.

PMID- 24729086
TI  - The association between the GSTP1 A313G and GSTM1 null/present polymorphisms and
      the treatment response of the platinum-based chemotherapy in non-small cell lung
      cancer (NSCLC) patients: a meta-analysis.
AB  - The relationship between the GSTP1 A313G and GSTM1 null/present polymorphisms and
      the treatment response (TR) of platinum-based chemotherapy in non-small cell lung
      cancer (NSCLC) patients have been extensively investigated by many studies, but
      the results were inconsistent and inconclusive. The aim of this meta-analysis was
      to further explore the predictive value of the GSTP1 and GSTM1 polymorphisms by
      collecting currently available evidence. Relevant studies were searched in
      PubMed, Embase, and CNKI. Inclusion criteria were NSCLC patients receiving
      platinum-based treatment, evaluated GSTP1 A313G or GSTM1 null/present
      polymorphisms, and TR. Odds ratio (OR) with 95 % confidence interval (CI) was
      calculated to assess the strength of the associations. Subgroup analysis by race
      was also conducted to explore the source of heterogeneity. A total of nine
      studies including 961 NSCLC patients were qualified for analysis. We found that
      GSTM1 null/present but not GSTP1 A313G polymorphism was associated with platinum
      based TR (for GSTM1, null vs present: OR = 1.77, 95% CI = 1.19-2.62). When
      subgroup analysis by race was done, both GSTP1 and GSTM1 polymorphisms were
      significantly associated with TR in East-Asian patients, but not in Caucasians.
      In addition, the heterogeneity disappeared in Asian and Caucasian patients when
      subgroup analysis by race was done. Our study suggested that the GSTP1 A313G and
      GSTM1 null/present polymorphisms could predict the treatment response of the
      platinum-based chemotherapy in NSCLC patients, especially in East-Asian patients.

PMID- 24729087
TI  - CD 152 gene polymorphisms and risk of osteosarcoma in Chinese population.
AB  - Osteosarcoma has become a health threat for adolescents and young adults. To
      identify the genetic risk factor for the malignancy is in urgent need. Several
      studies have investigated the role of CD 152 polymorphisms in osteosarcoma in a
      sample of Chinese population. However, the association is poorly defined due to
      lack of a sufficiently large sample. In this study, we performed a meta-analysis
      of all CD 152 polymorphisms that had been implicated in osteosarcoma to examine
      the association. We searched the electronic MEDLINE database until December 31,
      2013, to identify the studies regarding the association between CD 152
      polymorphisms and osteosarcoma. Inclusion criteria were followed in the selection
      of eligible study. The genotypic and allelic data were collected from all studies
      included to evaluate the risk of osteosarcoma (odds ratio, OR). We found
      statistically significant evidence of the studied CD 152 polymorphisms and
      increased risk of osteosarcoma in homozygous (OR = 1.79, 95 % CI = 1.40-2.29, P =
      0.958), recessive (OR = 1.77, 95 % CI = 1.40-2.25, P = 0.899), and allele model
      (OR = 1.21, 95 % CI = 1.09-1.34, P = 1.000). This increased risk was also
      revealed in single nucleotide polymorphism (SNP) +49G>A and SNP 326G>A. Our meta
      analysis indicates that there may be an association between CD 152 polymorphisms
      and risk of osteosarcoma in Chinese population. Further validation of the
      observation is necessary.

PMID- 24729088
TI  - Aberrant promoter methylation of the vimentin gene may contribute to colorectal
      carcinogenesis: a meta-analysis.
AB  - This meta-analysis of published cohort studies was conducted to evaluate how
      closely the promoter methylation of the vimentin gene is correlated with the
      pathogenesis of colorectal carcinogenesis (CRC). The Web of Science (1945 ~
      2013), Cochrane Library Database (issue 12, 2013), PubMed (1966 ~ 2013), EMBASE
      (1980 ~ 2013), CINAHL (1982 ~ 2013), and Chinese Biomedical Database (CBM) (1982
      ~ 2013) were searched without language restrictions. Meta-analyses were conducted
      using Stata software (Version 12.0, Stata Corporation, College Station, TX, USA).
      Odds ratios (ORs) and 95 % confidence intervals (95 %CI) were calculated. Seven
      clinical cohort studies with a total of 467 CRC subjects met our inclusion
      criteria. Our meta-analysis results demonstrated that the frequency of vimentin
      promoter methylation in cancer tissues was significantly higher than in normal
      and benign tissues (cancer tissues vs. normal tissues: OR = 32.41, 95 %CI = 21.04
      ~ 49.93, P < 0.001; cancer tissues vs. benign tissues: OR = 1.60, 95 %CI 1.05 ~
      2.42, P = 0.028). Ethnicity-stratified analysis indicated that the frequency of
      aberrant vimentin promoter methylation was correlated with the pathogenesis of
      CRC in both Asians and Caucasians. The findings of our meta-analysis confirm that
      vimentin methylation may play a crucial role in the pathogenesis of CRC.

PMID- 24729089
TI  - Influence of different hypoxia models on metastatic potential of SGC-7901 gastric
      cancer cells.
AB  - Gastric cancers are one of the most common gastrointestinal tumors with
      proclivity to metastasis. Hypoxia is an important feature in solid tumor
      microenvironment; accumulating evidence suggests that chronic and repetitive
      exposure to hypoxia and reoxygenation seems to provide an advantage to tumor
      growth. However, mechanisms of intermittent hypoxia regulating gastric cancer
      metastatic potential remain to be elucidated. In the present study, we
      established the continuous and intermittent gastric cancer hypoxia models, and we
      compared the effects of these models on gastric cancer cell metastatic potential.
      Hypoxia-inducible factor-1alpha (HIF-1alpha) and hypoxia target protein/genes
      expression in response to different hypoxia models were analyzed by Western blot,
      immunofluorescence, and real-time PCR assays. Gastric cancer cell migration and
      invasion ability were analyzed by wound healing and Boyden chamber assay. Colony
      formation and tumor spheroid formation assays were used to assess the ability of
      self-renewal. Stem-related protein OCT4 and HIF-1alpha expression were also
      analyzed by confocal immunofluorescence in single tertiary generation spheroid.
      We demonstrated that the intermittent hypoxia model upregulated expression of
      both HIF-1alpha and hypoxia target protein/genes in a time-dependent manner
      compared with that of SGC-7901 cells cultured under normoxia. Remarkably, HIF
      1alpha protein was more prone to being located in the nucleus of SGC-7901 cells
      under conditions of intermittent hypoxia. Gastric cancer cells' migration and
      invasion ability were significantly enhanced after hypoxic culture; moreover,
      intermittent hypoxia-conditioned SGC-7901 cells exhibited higher invasiveness
      than the continuous hypoxia-conditioned SGC-7901 cells. Gastric cancer
      stem/progenitor cell subpopulation was also enlarged which indicated an enhanced
      self-renewal ability in hypoxic cultured SGC-7901 cells. Our study emphasizes the
      significance of hypoxia in regulating gastric cancer cell metastasis potential.
      Compared with continuous hypoxia, intermittent hypoxia is a more effective and
      potent hypoxic stimulus. These results provide a new insight to investigate the
      hypoxic microenvironment within solid tumors. 

PMID- 24729090
TI  - Abnormal FHIT protein expression may be correlated with poor prognosis in gastric
      cancer: a meta-analysis.
AB  - Our current meta-analysis is aimed to investigate the relationships between
      fragile histidine triad (FHIT) protein expression and prognosis in gastric cancer
      patients. We searched 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) without any
      language restrictions. The meta-analysis was conducted using the STATA 12.0
      software. Crude hazard ratios (HR) with its 95 % confidence interval (95 % CI)
      were calculated. Eight clinical cohort studies with a total of 1,361 gastric
      cancer patients were involved in our meta-analysis. Our results revealed that
      FHIT-negative patients exhibited a shorter overall survival (OS) time than FHIT
      positive patients (HR = 1.23, 95 % CI = 1.01 ~ 1.44, P < 0.001). Ethnicity
      stratified analysis demonstrated that FHIT-negative patients have significantly
      poorer prognosis than FHIT-positive patients among both Caucasians and Asians
      (all P < 0.05). In conclusion, our meta-analysis provides evidences that negative
      expression of FHIT protein may be correlated with poor prognosis in patients with
      gastric cancer. Thus, FHIT expression level may be utilized as an independent
      prognostic marker for gastric cancer.

PMID- 24729092
TI  - Shared governance: a way to improve the care in an inpatient rehabilitation
      facility.
AB  - BACKGROUND: Rehabilitation care is specialized and individualized requiring
      effective and efficient communication to achieve optimal patient outcomes.
      PURPOSE: To examine how effective implementation of shared governance could
      improve care delivery, promote patient-centered care, and improve patient
      outcomes. DESIGN: The shared governance approach included all members of the
      rehabilitation team (i.e., physical therapist, occupational therapist, speech
      therapist, registered nurse and nurse aide) and was implemented over 6 months.
      FINDINGS/CONCLUSIONS: The major end products of this shared governance effort
      were improved staff communication, problem solving, patient outcomes, and staff
      satisfaction on our stroke and brain injury unit. CLINICAL RELEVANCE: When
      effectively implemented and sustained, shared governance between all
      rehabilitation team stakeholders can increase the effectiveness of communication
      along with more positive patient and staff outcomes.

PMID- 24729093
TI  - Silencing of Hsp70 intensifies 6-OHDA-induced apoptosis and Hsp90 upregulation in
      PC12 cells.
AB  - By the current study, we tried to find out the interactive mechanisms enrolled by
      Hsp70 and Hsp90 following the 6-hydroxydopamine (6-OHDA)-induced oxidative
      stress. Of heat shock protein (Hsp) family, we have previously evaluated the
      effects of Hsp90 gene silencing on in vitro model of Parkinson's disease and its
      influence on controlling the mechanisms of cell survival. Here, we extended our
      study to Hsp70 silencing short interfering RNA (siRNA) oligonucleotides,
      transfected into Pheochromocytoma (PC12) cells with/without exposure to 6-OHDA
      stress. In order to determine the probable effects of Hsp70 silencing on
      apoptotic factors, we assessed Bcl2/Bax ratio, nuclear level of PARP, and
      cleavage of caspase-3 under 6-OHDA stress condition. The results showed
      deteriorated effect of Hsp70 siRNA on apoptosis in cells exposed to only 6-OHDA.
      This is, at least in part, in consequence of upregulation of Hsp90, both at
      messenger RNA (mRNA) and protein levels. These data highlight the critical role
      of Hsp70 for cell survival under 6-OHDA stress condition. It could be a
      suggestive issue for supervision of caspase cascades by survival roles of Hsps as
      Hsp70 silencing resulted in apoptosis phenomenon. Convergence of Hsp70 anti
      apoptotic and 6-OHDA pro-apoptotic pathways may explain intensified apoptosis
      following Hsp70 silencing. In addition, nuclear factor erythroid-2-related factor
      2 (Nrf2), a transcription factor, has been previously studied in detoxification
      of oxidative stress. For this issue, we tried to elucidate Hsp70 silencing impact
      on Nrf2, which has been shown to regulate the transcription of Hsp70,
      unspecifically. Besides, our investigations revealed that Hsp70 siRNA did not
      affect the level of Nrf2 during 6-OHDA exposure. But, it is still a dealing
      question and other investigations are needed to have a comprehensive perception
      of Hsp family signaling functions. 

PMID- 24729095
TI  - Intratympanic gentamicin as a treatment for drop attacks in patients with
      Meniere's disease.
AB  - OBJECTIVES/HYPOTHESIS: Vertigo attacks in most cases of Meniere's disease (MD)
      are successfully treated with lifestyle changes and medication. However,
      approximately 6% of patients with MD develop drop attacks (DAs), a potentially
      life-threatening condition. Traditional treatment for DAs has been surgical
      labyrinthectomy. The objective of this study was to assess the effectiveness of
      intratympanic gentamicin for DAs in patients with MD. STUDY DESIGN: Retrospective
      charts review. METHODS: All charts were reviewed from Meniere DA patients at our
      hospital during the 10-year period from 2002 to 2012 who had been treated with
      intratympanic gentamicin and had been followed for at least 1 year afterward.
      RESULTS: Twenty-four ears fulfilled inclusion criteria. The time for
      manifestation of DAs varied from 1 to 20 years after diagnosis (mean 10 years). A
      total of 83.3% of ears with intractable MD and DA achieved complete symptom
      control of DAs after the first intratympanic gentamicin cycle and 95.8% after the
      further injections. Among patients with no DA recurrence by the end of the study
      follow-up, the symptom-free interval varied from 12 to 120 months (mean: 43.5
      months). All 15 patients with >= 24 months follow-up were still free of DAs.
      Elevated or absent vestibular evoked myogenic potential thresholds were more
      common in DA than in contralateral ears, and hearing loss was not a major
      complication of the treatment. CONCLUSION: Intratympanic gentamicin treatment
      appears to be a long-lasting and effective treatment for MD with DAs.

PMID- 24729094
TI  - Understanding HIV compartments and reservoirs.
AB  - The spectrum of HIV-1 cellular reservoirs is highly diversified, and their role
      varies according to the milieu of the anatomical sites in which the virus
      replicates. In this light, mechanisms underlying HIV-1 persistence in anatomical
      compartments may be profoundly different from what is observed in peripheral
      blood. This scenario is further complicated by sub-optimal drug penetration in
      tissues allowing persistent and cryptic HIV-1 replication in body districts
      despite undetectable viremia. On this basis, this review aims at providing recent
      insights regarding the critical role of HIV-1 cellular reservoirs in different
      anatomical compartments, and their relationship with the pathogenesis of HIV-1
      infection. A comprehensive definition of the complex interplay between the virus
      and its reservoir is critical in order to set up prophylactic and therapeutic
      strategies aimed at achieving the maximal virological suppression and hopefully
      in the near future the cure of HIV-1 infection (either functional or biological).

PMID- 24729096
TI  - Segmented flow is controlling growth of catalytic biofilms in continuous
      multiphase microreactors.
AB  - Biofilm reactors are often mass transfer limited due to excessive biofilm growth,
      impeding reactor performance. Fluidic conditions play a key role for biofilm
      structural development and subsequently for overall reactor performance.
      Continuous interfacial forces generated by aqueous-air segmented flow are
      controlling biofilm structure and diminish mass transfer limitations in biofilm
      microreactors. A simple three step method allows the formation of robust biofilms
      under aqueous-air segmented flow conditions: a first-generation biofilm is
      developing during single phase flow, followed by the introduction of air segments
      discarding most of the established biofilm. Finally, a second-generation, mature
      biofilm is formed in the presence of aqueous-air segments. Confocal laser
      scanning microscopy experiments revealed that the segmented flow supports the
      development of a robust biofilm. This mature biofilm is characterized by a three
      to fourfold increase in growth rate, calculated from an increase in thickness, a
      faster spatial distribution (95% surface coverage in 24 h), and a significantly
      more compact structure (roughness coefficient <1), as compared to biofilms grown
      under single phase flow conditions. The applicability of the concept in a
      segmented flow biofilm microreactor was demonstrated using the epoxidation of
      styrene to (S)-styrene oxide (ee > 99.8%) catalyzed by Pseudomonas sp. strain
      VLB120DeltaC cells in the mono-species biofilm. The limiting factor affecting
      reactor performance was oxygen transfer as the volumetric productivity rose from
      11 to 46 g L tube (-1) day(-1) after increasing the air flow rate. In summary,
      different interfacial forces can be applied for separating cell attachment and
      adaptation resulting in the development of a robust catalytic biofilm in
      continuous microreactors.

PMID- 24729097
TI  - Do sleep disorders play a role in pre-eclampsia?

PMID- 24729098
TI  - BWH emergency radiology-surgical correlation: omental hematoma with active
      extravasation: a rare diagnosis.
AB  - We describe the radiological and intraoperative correlation of a large omental
      hematoma with active intra-abdominal bleeding secondary to omental lacerations in
      a 75-year-old man following blunt trauma from a motor vehicle accident. The
      purpose of this article is to emphasize the importance of recognizing omental and
      mesenteric injuries in trauma patients, as these injuries are rare and can be
      overlooked on CT. 

PMID- 24729099
TI  - Effects of Religious Behavior on Health-Related Lifestyles of Muslims in
      Malaysia.
AB  - Religion has become more prominent in shaping attitudes and behavior, but little
      empirical information is available on the impact of religious behavior in shaping
      individual Muslims' health-related lifestyle behaviors in developing countries.
      The present study explores the relationship between religious behavior and the
      health-related practices of Malaysian Muslims. A convenience sample of 176
      Malaysian Muslims was collected through a self-administered questionnaire.
      Structural equation modeling was used to develop the model. Result shows that
      health-related actions are strongly influenced, both directly and indirectly, by
      the health-related lifestyle choices consumers engaging in on a daily basis in
      accordance with Islamic teachings. 

PMID- 24729100
TI  - Piperlongumine, an alkaloid causes inhibition of PI3 K/Akt/mTOR signaling axis to
      induce caspase-dependent apoptosis in human triple-negative breast cancer cells.
AB  - The phosphatidylinositol 3-kinase (PI3 K)/Akt/mammalian target of rapamycin
      (mTOR) signaling axis plays a central role in cell proliferation, growth and
      survival under physiological conditions. However, aberrant PI3 K/Akt/mTOR
      signaling has been implicated in many human cancers, including human triple
      negative breast cancer. Therefore, dual inhibitors of PI3 K/Akt and mTOR
      signaling could be valuable agents for treating breast cancer. The objective of
      this study was to investigate the effect of piperlongumine (PPLGM), a natural
      alkaloid on PI3 K/Akt/mTOR signaling, Akt mediated regulation of NF-kB and
      apoptosis evasion in human breast cancer cells. Using molecular docking studies,
      we found that PPLGM physically interacts with the conserved domain of PI3 K and
      mTOR kinases and the results were comparable with standard dual inhibitor
      PF04691502. Our results demonstrated that treatment of different human triple
      negative breast cancer cells with PPLGM resulted in concentration- and time
      dependent growth inhibition. The inhibition of cancer cell growth was associated
      with G1-phase cell cycle arrest and down-regulation of the NF-kB pathway leads to
      activation of the mitochondrial apoptotic pathway. It was also found that PPLGM
      significantly decreased the expression of p-Akt, p70S6K1, 4E-BP1, cyclin D1, Bcl
      2, p53 and increased expression of Bax, cytochrome c in human triple-negative
      breast cancer cells. Although insulin treatment increased the phosphorylation of
      Akt (Ser473), p70S6K1, 4E-BP1, PPLGM abolished the insulin mediated
      phosphorylation, it clearly indicates that PPLGM acts through PI3 k/Akt/mTOR
      axis. Our results suggest that PPLGM may be an effective therapeutic agent for
      the treatment of human triple negative breast cancer. 

PMID- 24729101
TI  - Vancomycin iontophoresis of allograft bone.
AB  - OBJECTIVES: The most concerning infection of allografts and operative procedures
      is methicillin resistant Staphylococcus aureus (MRSA) and no current
      iontophoresed antibiotics effectively combat this microbe. It was initially
      hypothesised that iontophoresis of vancomycin through bone would not be effective
      due to its large molecular size and lack of charge. The aim of this study was to
      determine whether this was a viable procedure and to find the optimum conditions
      for its use. METHODS: An iontophoresis cell was set up with varying
      concentrations of Vancomycin within the medulla of a section of sheep tibia,
      sealed from an external saline solution. The cell was run for varying times,
      Vancomycin concentrations and voltages, to gain information on optimisation of
      conditions for impregnating the graft. Each graft was then sectioned and dust
      ground from the exposed surface. The dust was serially washed to extract the
      Vancomycin and concentrations measured and plotted for all variables tested.
      RESULTS: Vancomycin was successfully delivered and impregnated to the graft using
      the iontophoresis technique. The first order fit to the whole data set gave a
      significant result (p = 0.0233), with a significant concentration (p = 0.02774)
      component. The time component was the next most significant (p = 0.0597), but did
      not exceed the 95% confidence level. CONCLUSIONS: Iontophoresis is an effective
      method for delivering Vancomycin to allograft bone. The concentrations of the
      vancomycin solution affected the bone concentration, but results were highly
      variable. Further study should be done on the effectiveness of delivering
      different antibiotics using this method. Cite this article: Bone Joint Res
      2014;3:101-7.

PMID- 24729102
TI  - Effects of alpha lipoic acid supplementation on serum levels of IL-8 and TNF
      alpha in patient with ESRD undergoing hemodialysis.
AB  - BACKGROUND: Chronic renal failure is a progressive and irreversible loss of
      kidney function, and the hemodialysis (HD) is one of the most common modalities
      in this regard. Oxidative stresses [like interleukin-8 (IL-8) and tumor necrosis
      factor-alpha (TNF-alpha)] and inflammation are the main risk factors associated
      with cardiovascular diseases and other complications in many organs in
      hemodialysis patients; meanwhile, antioxidants like alpha lipoic acid (ALA) may
      reduce the oxidative stress markers and the levels of inflammatory cytokines, so
      can improve of the patient's quality of life. METHODS: In this randomized
      clinical trial study, 60 HD patients were randomly categorized in two case and
      control groups. Case group received a daily capsule of 600 mg of ALA
      supplementation for 8 weeks, and the control group received placebo capsules
      daily. The serum level of IL-8 and TNF-alpha was measured in both groups before
      and after the intervention. RESULTS: There were no significant differences in
      age, gender, duration of dialysis, and causative factor for dialysis between both
      groups (P > 0.05). The mean of IL-8 and TNF-alpha after the intervention in case
      group was 26.20 +/- 15.34 and 21.25 +/- 9.61, respectively; the difference
      between both groups was not statistically significant (P > 0.05). CONCLUSION:
      Based on the better feeling and other beneficial effects of ALA were found in our
      study; we can conclude that it is a beneficial and recommended supplement,
      especially, for diabetic and dialysis patients.

PMID- 24729103
TI  - Novel technique for the treatment of large subcapsular renal hematoma: combined
      use of percutaneous drainage and urokinase injection.
AB  - PURPOSE: To evaluate the efficacy and safety of combined use of percutaneous
      drainage and urokinase injection to treat patients with large subcapsular renal
      hematoma. METHODS: We retrospectively analyzed the data of 20 patients with large
      subcapsular renal hematoma who were treated with percutaneous drainage and
      urokinase at our institutes between 2002 and 2010. Percutaneous drainage of the
      hematoma was performed after bleeding stopped. Then, urokinase was injected into
      the hematoma cavity per our protocol every 3 days. During the treatment and
      follow-up period, the diameter of hematoma was assessed by ultrasonography and
      enhanced computed tomography (CT) in all cases. Complete blood count, serum
      creatinine and blood pressure were evaluated as well. Follow-up periods ranged
      from 12 to 60 months (mean 24.1 +/- 11.5 months). RESULTS: Percutaneous renal
      hematoma drainage combined with urokinase injection was successfully performed in
      all the patients. After sufficient drainage, all of the patients were free from
      their symptoms. The average time to pain relief was 10.8 +/- 2.1 days after
      percutaneous drainage, and the total duration of drainage was 28 +/- 5.1 days.
      Relative to baseline, there was reduction in the diameter of hematoma evaluated
      by the enhanced CT scan after treatment (from 11.7 +/- 3.1 to 2.8 +/- 1.0 cm).
      During long-term follow-up, active bleeding, hypertension, renal function
      impairment or infectious complications were not found. CONCLUSIONS: This study
      revealed that combined use of percutaneous drainage and urokinase injection was a
      safe and effective treatment for patient with large subcapsular renal hematoma.

PMID- 24729104
TI  - Resistance exercise: a strategy to attenuate inflammation and protein-energy
      wasting in hemodialysis patients?
AB  - PURPOSE: Patients undergoing hemodialysis (HD) present persistent inflammation
      and protein-energy wasting (PEW), which contributes to high rates of mortality.
      This study aimed to assess the effects of a resistance exercise training program
      (RETP) on inflammation and PEW in HD patients. METHODS: Thirty-seven patients
      (56.7 % men, 45.9 +/- 14.1 years, 23.5 +/- 3.9 kg/m(2)) performed 6 months of
      intradialytic RETP. Plasma adhesion molecules levels (ICAM-1 and VCAM-1) were
      measured using the enzyme immunometric assay, and interleukin-6 (IL-6), C
      reactive protein, and tumor necrosis factor-alpha by ELISA. Anthropometric,
      physical capacity, and PEW (simultaneously presence of: BMI <23 kg/m(2), serum
      albumin <3.8 g/dL, and reduced arm muscle area) were analyzed. RESULTS: There was
      a reduction of ICAM-1 [(1,934.1 pg/mL (1,031.8-2,875.0) vs. 1,571.1 pg/mL (447.1
      2,985.5), p < 0.05], VCAM-1 [5,259.51 pg/mL (3,967.4-6,682.4) vs. 3,062.11 pg/mL
      (2,034.0-5,034.4), p < 0.05], and CRP levels (2.3 +/- 0.9 to 1.6 +/- 0.6 pg/mL, p
      < 0.001) after 6 months of RETP. Body composition improved, albumin increased
      (3.7 +/- 0.3 to 3.9 +/- 0.2, p < 0.05), and the number of patients presenting PEW
      was decreased (p = 0.005). CONCLUSIONS: Resistance exercise program for 6 months
      seems to be effective in reducing inflammation and PEW of HD patients. The
      universal trial number of this study is U1111-1139-1326.

PMID- 24729105
TI  - Personalised medicine, disease prevention, and the inverse care law: more harm
      than benefit?

PMID- 24729106
TI  - Invisibility of moving objects: a core symptom of motion blindness.
AB  - Although the higher brain mechanisms of seeing moving objects have been deeply
      investigated, motion blindness remains a rare and enigmatic symptom. Very few
      case reports well describe the detailed symptoms and the lesions. We report a
      case of a patient who presented with invisibility of moving objects, that is,
      motion blindness resulting from a unilateral right hemispheric lesion. This man,
      in his 60s, suffered persistent motion blindness from a unilateral right
      temporoparietal subcortical haemorrhage. He could not see the moving objects,
      just felt the objects 'disapper' when they began moving. The symptom was observed
      not only in his daily life but also during investigations in the hospital. To the
      best of our knowledge, this is the first report of a patient who showed
      persistent motion blindness with a right unilateral lesion, and only the second
      one with clinically apparent motion blindness, whose symptoms were similar to
      those of the first reported case. 

PMID- 24729107
TI  - Recurrent fevers in children: TRAPS for young players.
AB  - We present the case of an 11-month-old girl who presented with recurrent febrile
      episodes and was found to have tumour necrosis factor receptor-associated
      periodic syndrome due to a novel mutation in the TNFRSF1A gene. The concept of
      autoinflammatory diseases is discussed and the management of this condition
      reviewed. 

PMID- 24729108
TI  - Self-inflicted herpetic whitlow.
AB  - A 25-year-old dental radiographer reported to the outpatient department with
      lesions at the lower and upper lips which had later spread to his finger. On the
      basis of the given history and clinical features, a diagnosis of primary herpetic
      infection on the mouth followed by secondary infection on the finger was made and
      the patient was advised systemic and topical antiviral therapy following which
      his lesions healed uneventfully. 

PMID- 24729109
TI  - An erupted compound odontoma.
AB  - Odontomas are familiar entities but their eruption into the oral cavity is an
      extraordinary occurrence, which may be associated with pain, infection,
      malocclusion, etc. Not many cases of erupted odontomas have been reported in the
      literature. This paper puts forth a case of erupting odontoma in an attempt to
      add to the list of reported cases of this unique pathology. 

PMID- 24729110
TI  - Primary low-grade diffuse small lymphocytic lymphoma of the central nervous
      system.
AB  - A 45-year-old Indian woman presented in neurosurgery outpatient with seizures,
      headache and vomiting for the past 1 month. MRI of the brain was suggestive of a
      malignant central nervous system (CNS) tumour. Histological and
      immunohistochemical examinations of stereotactic biopsy of the tumour were
      diagnostic of a low-grade diffuse small lymphocytic lymphoma of the CNS. No
      evidence of any occult systemic lymphoma was observed, confirming its 'primary'
      origin in the CNS. The diagnosis of a low-grade primary CNS lymphoma (PCNSL) is
      difficult as clinical and neuroradiological features are wide and variable. The
      clinical course is more indolent than a high-grade PCNSL and thus, a less
      aggressive and localised targeted treatment could be sufficient rather than the
      high dose, neurotoxic methotrexate-based chemotherapeutic treatment, recommended
      for high-grade PCNSL. Histological and immunohistological confirmation is
      therefore mandatory for early, appropriate treatment and prognostic implications.

PMID- 24729111
TI  - Amiodarone-induced myxoedema coma.
AB  - A 62-year-old man was found to have bradycardia, hypothermia and respiratory
      failure 3 weeks after initiation of amiodarone therapy for atrial fibrillation.
      Thyroid-stimulating hormone was found to be 168 MUIU/mL (nl. 0.3-5 MUIU/mL) and
      free thyroxine (FT4) was <0.2 ng/dL (nl. 0.8-1.8 ng/dL). He received intravenous
      fluids, vasopressor therapy and stress dose steroids; he was intubated and
      admitted to the intensive care unit. He received 500 MUg of intravenous
      levothyroxine in the first 18 h of therapy, and 150 ug intravenous daily
      thereafter. Haemodynamic improvement, along with complete recovery of mental
      status, occurred after 48 h. Twelve hours after the initiation of therapy, FT4
      was 0.96 ng/dL. The patient was maintained on levothyroxine 175 (g POorally
      daily. A thyroid ultrasound showed diffuse heterogeneity. The 24 hour excretion
      of iodine was 3657 (mcg (25-756 ( mcg). The only two cases of amiodarone-induced
      myxoedema coma in the literature report patient death despite supportive therapy
      and thyroid hormone replacement. This case represents the most thoroughly
      investigated case of amiodarone-induced myxoedema coma with a history significant
      for subclinical thyroid disease. 

PMID- 24729112
TI  - QT prolongation in a child with thyroid storm.
AB  - A 12-year-old girl presented with an acute confusional state and a 2-year history
      of weight loss, anxiety, agitation and recurrent fever. Thyroid function tests
      confirmed severe hyperthyroidism, and a diagnosis of thyroid storm was made
      (Burch and Wartofsky score=75). ECG showed a prolonged QTc interval of 506 ms.
      Acute treatment for thyroid storm consisted of Lugol's iodine, prednisolone,
      carbimazole and propranolol. She made a steady recovery and by 3 months her
      thyroid function had normalised; a repeat ECG showed a QTc within the normal
      range (430 ms). There was no relevant family history. This is a case of QTc
      prolongation with hyperthyroidism and normalisation with euthyroidism. It is not
      commonly recognised that hyperthyroidism in children may be associated with QTc
      prolongation. QTc measurement should be incorporated into management protocols
      for hyperthyroidism. 

PMID- 24729113
TI  - Metastatic bone lesion due to methotrexate and etanercept 24 years after breast
      cancer treatment.
AB  - A 72-year-old woman with rheumatoid arthritis presented with lumbar vertebral
      bone metastasis 24 years after mammectomy and radiotherapy for breast cancer. She
      was treated with prednisolone and methotrexate (MTX) for 11 months to which 10 mg
      of etanercept twice a week was added for a further 8 months. On the basis of this
      result, the possibility of a metastatic bone lesion appearing many years after
      cancer treatment should be considered when planning MTX and etanercept therapy. 

PMID- 24729114
TI  - Osseous haemophilic pseudotumour and concurrent primary hyperparathyroidism: a
      diagnostic conundrum.
AB  - Pseudotumours are rare, occurring in 1-2% of severe haemophiliacs. Osseous
      locations are far less frequent than soft tissue location. We report a case of a
      43-year-old man with haemophilia A, who presented with a gradually enlarging left
      thigh mass for 8 months. There were no constitutional symptoms. Plain radiograph
      showed an expansile lytic lesion with 'soap-bubble' appearance arising from the
      left femur diaphysis. On MRI, it appeared as a non-enhancing, multilobulated
      lesion expanding the medullary and subperiosteal spaces. The mass exhibited
      concentric ring sign with heterogeneous intermediate signal intensity in the core
      lesion, reflective of chronic haematoma with blood degradation products of
      different stages. A diagnosis of haemophilic pseudotumour was made.
      Hypercalcaemia, however, raised a diagnostic dilemma as bone malignancy needed to
      be considered. An open excisional biopsy and subsequent amputation confirmed the
      diagnosis of osseous haemophilic pseudotumour. Nuclear medicine study later
      revealed a concurrent parathyroid adenoma. 

PMID- 24729115
TI  - Acute double flexor tendon ruptures following injection of collagenase
      clostridium histolyticum (Xiapex) for Dupuytren's contracture.
AB  - We report a case of acute (24 h) double flexor tendon rupture of the little
      finger after a single injection of collagenase clostridium histolyticum into a
      palmar Dupuytren's contracture cord which caused metacarpophalangeal joint
      contracture. Tendon surgery was performed 48 h postinjury with primary repair and
      standard rehabilitation but it resulted in poor active flexion due to adhesions.
      Previous papers have suggested that a needle inserted into the flexor tendon can
      be detected prior to the injection of collagenase by asking the patient to
      actively move the finger, but our test on an awake patient showed that when a 27
      gauge needle was inserted into the flexor tendons through a thick palmar cord,
      the syringe did not move significantly when the patient moved the finger, and
      therefore this test does not minimise the risk of iatrogenic tendon injury when
      using collagenase (Xiapex) for Dupuytren's contracture. 

PMID- 24729116
TI  - Pituitary metastasis from breast cancer presenting as diabetes insipidus.
AB  - An 83-year-old woman developed pituitary metastasis while being treated for
      metastatic breast cancer. She presented with visual disturbance and headache
      followed by thirst, nocturia and polyuria. A visual field defect was present. MRI
      revealed a sellar mass consistent with metastasis to the pituitary gland. She was
      successfully treated with radiotherapy to the sella and had improvement of her
      visual symptoms and visual field defect. She then required ongoing treatment for
      diabetes insipidus. Her symptoms had not shown any sign of recurring up to 9
      months after treatment. Pituitary metastases are rare but should be suspected in
      patients with metastatic cancer who present with features similar to those seen
      here. With improvements in survival in metastatic breast cancer, pituitary
      metastases may be seen more commonly and active local treatment is warranted
      given the possibility of resolution of symptoms related to the pituitary
      metastases. 

PMID- 24729117
TI  - Acute myocardial infarction following honeybee sting.
AB  - The occurrence of acute myocardial infarction following a honeybee sting has been
      very rarely reported in the previous literature. Possible pathogenetic mechanisms
      include severe hypotension, rarely hypertension and coronary vasospasm with
      subsequent thrombosis of coronary vessels developed after the release of
      vasoactive, inflammatory and thrombogenic substances contained in the bee venom.
      This syndrome is also known as Kounis syndrome. We report a case of a 32-year-old
      man who presented with acute inferior wall myocardial infarction within 3 h of
      honeybee sting. He was treated with thrombolytic therapy. Coronary angiogram
      revealed normal coronary arteries. 

PMID- 24729118
TI  - Haematological complete remission by ponatinib and bortezomib in a patient with
      relapsed, Ph+ pre-B acute lymphoblastic leukaemia.
AB  - A 74-year-old man was previously diagnosed with BCR-ABL1-positive pre-B cell
      acute lymphoblastic leukaemia (pre-B ALL) based on bone marrow cytology, flow
      cytometry, cytogenetics and fluorescent in situ hybridisation findings. Following
      a highly complicated hospital course, the patient achieved cytogenetic remission
      by consolidated chemotherapy and the tyrosine kinase inhibitor dasatinib. He
      subsequently presented with relapsed pre-B ALL after 3 years in remission. In
      consideration of his challenging clinical history, he was started on concurrent
      ponatinib (45 mg daily) and bortezomib (1.3 mg/m(2) intravenous weekly). The
      major molecular response was achieved (<0.0893% BCR-ABL1 transcripts) after 3
      months. Bone marrow now demonstrates a BCR-ABL1-negative, complete cytogenetic
      response. The patient continues to do well with mild thrombocytopenia and
      improved anaemia on bortezomib and 30 mg daily ponatinib. Our experience with a
      single patient suggests the feasibility of combined targeted therapy with
      ponatinib and bortezomib. This novel treatment approach achieved clinical
      remission with a manageable toxicity profile. 

PMID- 24729119
TI  - Amelanotic malignant melanoma of the cervical oesophagus.
AB  - We report the case of a young woman who presented with progressive dysphagia and
      swelling in the anterior aspect of the neck of short duration. On evaluation, she
      was diagnosed with amelanotic malignant melanoma of the cervical oesophagus. She
      underwent total laryngopharyngo-oesophagectomy with gastric transposition with
      bilateral modified radical neck dissection with feeding jejunostomy and a
      permanent tracheostomy with postoperative combined chemoradiation therapy.
      However, in spite of aggressive treatment, the patient expired 8 months after
      initial presentation with distant metastasis. 

PMID- 24729120
TI  - Adolescent right axillary accessory breast with galactorrhoea.

PMID- 24729122
TI  - Pitfalls of single lung transplantation (SLT) for chronic obstructive pulmonary
      disease.

PMID- 24729121
TI  - Hydatid cyst: unusual presentation as 'breast lump'.
AB  - Hydatid cyst in the breast is rare. We report a case of hydatid cyst in the
      breast in a 30-year-old Indian rural woman who presented with a lump in her left
      breast. MRI findings showed a cystic lesion in the breast. Histopathological
      examination showed features consistent with hydatid cyst with surrounding
      adherent pericystic breast tissue showing fibrocollagenisation and inflammatory
      response. ELISA for echinococcal antigen was also found to be positive. This case
      emphasises that preoperative diagnosis of hydatid cyst in the breast is difficult
      and often missed as the breast is a rare site of echinococcal infection and
      clinical and imaging findings are wide and non-specific. Cytological diagnosis by
      fine-needle aspiration may not always be possible. Therefore, hydatid cyst in the
      breast should always be considered in the differential diagnosis of a breast lump
      and histopathological confirmation is necessary for early and appropriate
      treatment. 

PMID- 24729123
TI  - Resistance training in hemodialysis patients: a review.
AB  - PURPOSE: Few studies have examined the role of resistance training (RT) in
      chronic kidney patients on hemodialysis (HD). This study reviews the literature
      about resistance exercise for patients on HD and describes protocols and clinical
      outcomes. METHODS: A search of the MEDLINE database found 21 eligible
      publications, of which 14 studies applied only RT and 7 combined RT and aerobic
      training. FINDINGS: Regarding the period of exercise training, 14 studies applied
      intradialytic exercise. The main outcome reported was muscle strength, which was
      assessed through knee strength and handgrip measures. CONCLUSIONS: All studies
      reviewed presented at least one significant result in relation to biochemical
      parameters, physical capacity, strength, body composition, or quality of life.
      CLINICAL RELEVANCE: This review demonstrates that RT improves muscle strength,
      some biochemical parameters, and quality of life of the HD patients.

PMID- 24729124
TI  - Deficiency in asparagine synthetase expression in rectal cancers receiving
      concurrent chemoradiotherapy: negative prognostic impact and therapeutic
      relevance.
AB  - Locally advanced rectal cancers are currently treated with neoadjuvant concurrent
      chemoradiotherapy (CCRT) followed by surgery, but risk stratification and final
      outcomes remain suboptimal. In this study, we identify and validate targetable
      metabolic drivers relevant to the prognosis of patients with rectal cancer
      treated with CCRT. Using a published transcriptome of rectal cancers, we found
      that asparagine synthetase (ASNS) gene significantly predicted the response to
      CCRT. From 172 patients with rectal cancer, the expression levels of ASNS, using
      immunohistochemistry assays, were further evaluated in tumor specimens initially
      obtained by using colonoscopy. Expression levels of ASNS were further correlated
      with major clinicopathological features and clinical survivals in this valid
      cohort. ASNS deficiency was significantly related to advanced posttreatment tumor
      (T3, T4; P = .015) and nodal status (N1, N2; P = .004) and inferior tumor
      regression grade (P < .001). In survival analyses, ASNS deficiency was
      significantly associated with shorter local recurrence-free survival (LRFS; P =
      .0039), metastasis-free survival (MeFS; P = .0001), and disease-specific survival
      (DSS; P = .0006). Furthermore, ASNS deficiency was independently predictive of
      worse outcomes for MeFS (P = .012, hazard ratio = 3.691) and DSS (P = .022,
      hazard ratio = 2.845), using multivariate analysis. ASNS deficiency is correlated
      with poor therapeutic response and worse survivals in patients with rectal cancer
      receiving neoadjuvant CCRT. These findings indicate that ASNS is a prognostic
      factor with therapeutic potential for treating rectal cancer.

PMID- 24729126
TI  - Obesity and the risk of cholangiocarcinoma: a meta-analysis.
AB  - A number of studies have shown that obesity is implicated in the susceptibility
      to several cancers. However, the association between obesity and
      cholangiocarcinoma remains unclear. This meta-analysis aimed to quantitatively
      assess the association between overweight or obesity and the incidence of
      cholangiocarcinoma. A literature search was performed for cohort and case-control
      studies published from 1996 to 2013 using PubMed, Cochrane, and EMBASE databases.
      Studies were included if they reported odds ratios (ORs) and corresponding 95 %
      confidence intervals (CIs) of cholangiocarcinoma with respect to obesity or
      overweight. Normal weight, overweight, and obesity were defined when the body
      mass index (BMI) was 18.5-24.9, 25-29.9, and >= 30 kg/m(2), respectively. Excess
      body weight was defined as BMI >= 25 kg/m(2). Ten studies met the inclusion
      criteria, which included five cohort and five case-control studies. Compared with
      normal weight, being overweight (pooled OR 1.30, 95 % CI 1.13-1.49), obesity
      (pooled OR 1.52, 95 % CI 1.13-1.89), and excess body weight (pooled OR 1.37, 95
      %CI 1.22-1.55) were significantly associated with cholangiocarcinoma. The funnel
      plot revealed no evidence for publication bias. Obesity is associated with the
      increased risk of cholangiocarcinoma, which needs to be confirmed by long-term
      cohort studies.

PMID- 24729125
TI  - Running for time: circadian rhythms and melanoma.
AB  - Circadian timing system includes an input pathway transmitting environmental
      signals to a core oscillator that generates circadian signals responsible for the
      peripheral physiological or behavioural events. Circadian 24-h rhythms regulate
      diverse physiologic processes. Deregulation of these rhythms is associated with a
      number of pathogenic conditions including depression, diabetes, metabolic
      syndrome and cancer. Melanoma is a less common type of skin cancer yet more
      aggressive often with a lethal ending. However, little is known about circadian
      control in melanoma and exact functional associations between core clock genes
      and development of melanoma skin cancer. This paper, therefore, comprehensively
      analyses current literature data on the involvement of circadian clock components
      in melanoma development. In particular, the role of circadian rhythm deregulation
      is discussed in the context of DNA repair mechanisms and influence of UV
      radiation and artificial light exposure on cancer development. The role of
      arylalkylamine N-acetyltransferase (AANAT) enzyme and impact of melatonin, as a
      major output factor of circadian rhythm, and its protective role in melanoma are
      discussed in details. We hypothesise that further understanding of clock genes'
      involvement and circadian regulation might foster discoveries in the field of
      melanoma diagnostics and treatment. 

PMID- 24729127
TI  - Changing trends of speech outcomes after total laryngectomy in the 21st century:
      a single-center study.
AB  - OBJECTIVES/HYPOTHESIS: To describe the speech rehabilitation outcomes of patients
      undergoing total laryngectomy (TL) in the 21st century. STUDY DESIGN:
      Retrospective chart review. SETTING: Tertiary academic center SUBJECTS AND
      METHODS: Retrospective review of 167 patients who underwent TL from June 2000 to
      February 2012. Demographics, disease variables, and surgical factors were
      reviewed. Primary alaryngeal speech modality, speech outcome, and
      tracheoesophageal puncture (TEP) complication rates were assessed. RESULTS:
      Overall TEP speech success rate (primary or secondary) was 72%. Overall TEP
      speech success rate was 76% for those with primary TEP and was 68% for those with
      secondary TEP. TEP speech success rates at first, second, and beyond second year
      were 75%, 72%, and 70%, respectively. Success rates for primary TL, salvage TL,
      primary TL with pharyngeal reconstruction, or salvage TL with pharyngeal
      reconstruction groups were 71%, 72%, 73%, and 71%, respectively. TEP-related
      complications occurred in 43% of patients, with no difference in complication
      rates between primary versus salvage TL or primary versus secondary TEP. For
      those with complications, TEP success rate was 65%. CONCLUSION: This study showed
      TEP speech-outcome success rates lower than what has been historically reported.
      There was no significant difference in TEP speech outcome between primary versus
      salvage TL or primary versus secondary TEP. Patients with TEP-related
      complications had TEP speech-outcome success rates comparable to those without
      any complication. TEP may continue to be a superior option as a mode of speech in
      patients with TL, including those undergoing salvage TL. LEVEL OF EVIDENCE: 4.

PMID- 24729129
TI  - The harm of male-on-female rape: a response to David Benatar.
AB  - This article attacks David Benatar's claim made in his 2012 book, The Second
      Sexism: Discrimination Against Men and Boys, that when an individual is the
      victim of violence it does not matter whether his or her perpetrator is of the
      same or a different sex. By exploring two related yet distinct phenomena, well
      documented in the empirical psychological literature, that I call "shattering"
      and "fragmentation," I argue that when a woman is raped, it does matter that her
      rapist is male, given that her situation as a woman under patriarchy is partly
      constitutive of the harm that she suffers. 

PMID- 24729130
TI  - Using propensity score matching to estimate an "unbiased effect-size" between
      women's employment and partner violence in Tanzania.
AB  - Estimates of the effect of employment on women's risk of partner violence in
      cross-sectional studies are subject to potential "self-selection bias." Women's
      personal choice of whether to pursue employment or not may create fundamental
      differences between the group of women who are employed and those who are not
      employed that standard regression methods cannot account for even after adjusting
      for confounding. The aim of this study is to demonstrate the utility of
      propensity score matching (PSM), a technique used widely in econometrics, to
      address this bias in cross-sectional studies. We use PSM to estimate an unbiased
      effect-size of women's employment on their risk of experiencing partner violence
      in urban and rural Tanzania using data from the 2010 Tanzania Demographic and
      Health Survey (DHS). Three different measures of women's employment were
      analyzed: whether they had engaged in any productive work outside of the home in
      the past year, whether they received payment in cash for this productive work,
      and whether their employment was stable. Women who worked outside of the home
      were significantly different from those who did not. In both urban and rural
      Tanzania, women's risk of violence appears higher among women who worked in the
      past year than among those who did not, even after using PSM to account for
      underlying differences in these two groups of women. Being paid in cash reversed
      this effect in rural areas whereas stability of employment reduced this risk in
      urban centers. The estimated size of effect varied by type of matching estimator,
      but the direction of the association remained largely consistent. This study's
      findings suggest substantial self-selection into employment. PSM methods, by
      compensating for this bias, appear to be a useful tool for estimating the
      relationship between women's employment and partner violence in cross-sectional
      studies. 

PMID- 24729128
TI  - Intriguing roles of hippocampus-synthesized 17beta-estradiol in the modulation of
      hippocampal synaptic plasticity.
AB  - Accumulated studies have shown that 17beta-estradiol (E2) can be de novo
      synthesized in the hippocampus, and its role in the regulation of hippocampal
      synaptic plasticity, which is the basis of learning and memory, has long been
      exploring. Steroidogenic enzymes (e.g., aromatase) that are essential to the
      hippocampus-synthesized synthesis of E2 have been detected in the hippocampus.
      Inhibition of E2 synthesis by aromatase inhibitors significantly reduces the
      density of hippocampal spine synapses, levels of some synaptic proteins such as
      spinopholin and synaptophysin. Moreover, the electrophysiological properties of
      hippocampal neurons are also changed in response to this inhibition. The
      influences of gonadal and hippocampal E2 on synaptic plasticity may exist some
      differences, since some reports showed that gonadal (or circulating) estrogens
      have no obvious effects in the modulation of hippocampal synaptic proteins as
      evidenced in some ovariectomized animals and postmenopausal women who suffered
      from Alzheimer's disease (AD). These evidences leads to a hypothesis that
      hippocampal E2 may play a more important role in modulation of synaptic
      plasticity than gonadal E2. The signaling pathways, whereby hippocampal E2
      modulates synaptic plasticity, insist of classical chronic genomic pathway and
      rapid nongenomic pathway, which mediated by nonnuclear estrogen receptor (GPER)
      and/or nuclear or nonnuclear estrogen receptors, which require coactivators for
      their transcription activity. Among which steroid receptor coactivator-1 (SRC-1)
      is the predominant coactivator p160 family members in the brain. Several clues
      have shown that SRC-1 is expressed in hippocampus and is highly correlated with
      some key synaptic proteins developmentally or after orchidectomy but not
      ovariectomy, indicating SRC-1 may be regulated by hippocampus-synthesized E2 and
      profoundly involved in the mediation of hippocampal E2 regulation of hippocampal
      synaptic plasticity. Further studies about the exact roles of hippocampus
      synthesized E2 and therefore SRC-1 are urgently needed in order to facilitate our
      understanding of hippocampal E2, which will be very important to the development
      of novel strategies of estrogen replacement therapy against neurodegenerative
      deficits such as Alzheimer's disease (AD). 

PMID- 24729131
TI  - Homeostasis and dynamic stability of the phenotype link robustness and
      plasticity.
AB  - Phenotypes are remarkably robust to genetic and environmental variation. Although
      the general control principles of robustness are well understood in simple
      systems, the actual mechanisms that convey robustness in realistically complex
      systems have been little studied. We have studied the origins and properties of
      robustness in a complex metabolic system that is relevant to human health: folate
      mediated one-carbon metabolism (FOCM). The FOCM network consists of several
      interlocking cycles, and reactions in the system contain the rate-limiting steps
      for DNA synthesis, the reactions for DNA methylation, and the synthesis of
      glutathione, the primary endogenous anti-oxidant. Defects in FOCM can arise from
      mutations in enzymes, or from nutritional deficiencies such as folic acid and
      vitamins B6 and B12, and are associated with birth defects, anemia,
      cardiovascular disease, and cancer. We show that this metabolic network has
      evolved as diverse homeostatic mechanisms that stabilize critical reactions
      against genetic and environmental variation. These mechanisms achieve stability
      dynamically, by continually altering some reaction rates in order to keep
      critical reactions stable. Robustness is a systems property and exists only in
      restricted regions of genotype space, and we show that natural standing genetic
      variation in human populations is concentrated in these regions. We show how
      genetic perturbations and/or environmental shifts that disrupt the homeostatic
      regime can increase phenotypic variation and the correlation between standing
      genetic variation and phenotypic variation. Robustness and stability are never
      perfect and, because they are maintained dynamically, can be readily perturbed by
      both genetic and environmental factors. The tightrope between stability and
      change sways easily and, through the release of genetic variation, may be an
      important enabler of rapid phenotypic evolution. Although we use examples from a
      metabolic system in which quantification of mechanism is particularly accessible,
      we note that the same principles obtain in other homeostatic systems in
      physiology and development. 

PMID- 24729133
TI  - Adolescents' beliefs about forced sex in KwaZulu-Natal, South Africa.
AB  - Gender-based violence has serious consequences for the psychological, physical,
      and sexual well-being of both men and women. Various gender roles, attitudes, and
      practices in South Africa create an environment that fosters submission and
      silence in females and hegemony and coercion in males. One of the expressions of
      this power inequity is a high prevalence of forced sex, which in its turn is
      associated with higher risk of HIV infection. This study therefore assessed
      potential gender differences in beliefs about forced sex and in prevalence of
      reported forced sex among high school students (N = 764) in KwaZulu-Natal.
      Results showed that significantly more boys were sexually active (26 %) than
      girls (12 %) and that boys experienced earlier sexual debut by over a year. Boys
      also held a more positive view about forced sex than girls since they associated
      it more often with signs of love, as an appropriate way to satisfy sexual urges,
      and as acceptable if the girl was financially dependent on the boy. The
      perception that peers and friends considered forced sex to be an effective way to
      punish a female partner was also more common among boys. On the other hand, boys
      were less knowledgeable about the health and legal consequences of forced sex,
      but no significant differences were found for other sociocognitive items, such as
      self-efficacy and behavioral intention items. Consequently, health education
      programs are needed to inform both boys and girls about the risks of forced sex,
      to convince boys and their friends about its inappropriateness and girls to
      empower themselves to avoid forced sex. 

PMID- 24729134
TI  - Experimental effects of exposure to pornography: the moderating effect of
      personality and mediating effect of sexual arousal.
AB  - Using a randomly selected community sample of 200 Danish young adult men and
      women in a randomized experimental design, the study investigated the effects of
      a personality trait (agreeableness), past pornography consumption, and
      experimental exposure to non-violent pornography on attitudes supporting violence
      against women (ASV). We found that lower levels of agreeableness and higher
      levels of past pornography consumption significantly predicted ASV. In addition,
      experimental exposure to pornography increased ASV but only among men low in
      agreeableness. This relationship was found to be significantly mediated by sexual
      arousal with sexual arousal referring to the subjective assessment of feeling
      sexually excited, ready for sexual activities, and/or bodily sensations
      associated with being sexually aroused. In underscoring the importance of
      individual differences, the results supported the hierarchical confluence model
      of sexual aggression and the media literature on affective engagement and priming
      effects. 

PMID- 24729132
TI  - Increasing the affinity of selective bZIP-binding peptides through surface
      residue redesign.
AB  - The coiled-coil dimer is a prevalent protein interaction motif that is important
      for many cellular processes. The basic leucine-zipper (bZIP) transcription
      factors are one family of proteins for which coiled-coil mediated dimerization is
      essential for function, and misregulation of bZIPs can lead to disease states
      including cancer. This makes coiled coils attractive protein-protein interaction
      targets to disrupt using engineered molecules. Previous work designing peptides
      to compete with native coiled-coil interactions focused primarily on designing
      the core residues of the interface to achieve affinity and specificity. However,
      folding studies on the model bZIP GCN4 show that coiled-coil surface residues
      also contribute to binding affinity. Here we extend a prior study in which
      peptides were designed to bind tightly and specifically to representative members
      of each of 20 human bZIP families. These "anti-bZIP" peptides were designed with
      an emphasis on target-binding specificity, with contributions to design-target
      specificity and affinity engineered considering only the coiled-coil core
      residues. High-throughput testing using peptide arrays indicated many successes.
      We have now measured the binding affinities and specificities of anti-bZIPs that
      bind to FOS, XBP1, ATF6, and CREBZF in solution and tested whether redesigning
      the surface residues can increase design-target affinity. Incorporating residues
      that favor helix formation into the designs increased binding affinities in all
      cases, providing low-nanomolar binders of each target. However, changes in
      surface electrostatic interactions sometimes changed the binding specificity of
      the designed peptides.

PMID- 24729135
TI  - "Bareback" pornography consumption and safe-sex intentions of men having sex with
      men.
AB  - Men having sex with men (MSM) commonly consume "bareback" pornography, which
      includes scenes of unprotected anal intercourse. Prior research on human
      imitative behavior suggests that these media might counteract efforts to promote
      safe-sex behaviors. To date, no studies have demonstrated a causal link between
      bareback pornography consumption and reduced safe-sex intentions. Study 1
      utilized a correlational design conducted as an online survey. Study 2 was set in
      an actual MSM sex club, using a 2 * 2 mixed-factorial design to compare type of
      pornography (unprotected vs. protected anal intercourse) and age of actors
      (younger vs. older). As the main dependent variable in both studies, participants
      self-reported their inclinations toward unprotected versus protected intercourse,
      using a 100-point sliding scale (1 = unprotected, 100 = protected). In Study 1,
      more attention to unprotected sex acts on actual DVD film covers predicted lower
      safe-sex intentions, as compared to other elements of the film cover. In Study 2,
      safe-sex intentions after viewing unprotected-sex films were lower than after
      viewing protected-sex films. The results provide novel and ecologically valid
      evidence that "bareback" pornography consumption impacts viewer's inclinations
      toward sexual risk-taking by lowering their intentions to use protected sex
      measures. Suggestions are given as to how these findings can be utilized for
      purposes of intervention and prevention of STI and HIV infections.

PMID- 24729136
TI  - Semicompeting risks in aging research: methods, issues and needs.
AB  - A semicompeting risks problem involves two-types of events: a nonterminal and a
      terminal event (death). Typically, the nonterminal event is the focus of the
      study, but the terminal event can preclude the occurrence of the nonterminal
      event. Semicompeting risks are ubiquitous in studies of aging. Examples of
      semicompeting risk dyads include: dementia and death, frailty syndrome and death,
      disability and death, and nursing home placement and death. Semicompeting risk
      models can be divided into two broad classes: models based only on observables
      quantities (class [Formula: see text]) and those based on potential (latent)
      failure times (class [Formula: see text]). The classical illness-death model
      belongs to class [Formula: see text]. This model is a special case of the
      multistate models, which has been an active area of methodology development.
      During the past decade and a half, there has also been a flurry of methodological
      activity on semicompeting risks based on latent failure times ([Formula: see
      text] models). These advances notwithstanding, the semicompeting risks
      methodology has not penetrated biomedical research, in general, and
      gerontological research, in particular. Some possible reasons for this lack of
      uptake are: the methods are relatively new and sophisticated, conceptual problems
      associated with potential failure time models are difficult to overcome, paucity
      of expository articles aimed at educating practitioners, and non-availability of
      readily usable software. The main goals of this review article are: (i) to
      describe the major types of semicompeting risks problems arising in aging
      research, (ii) to provide a brief survey of the semicompeting risks methods,
      (iii) to suggest appropriate methods for addressing the problems in aging
      research, (iv) to highlight areas where more work is needed, and (v) to suggest
      ways to facilitate the uptake of the semicompeting risks methodology by the
      broader biomedical research community. 

PMID- 24729137
TI  - Current state-of-the-art and future perspectives of robotic technology in
      neurosurgery.
AB  - Neurosurgery is one of the most demanding surgical specialties in terms of
      precision requirements and surgical field limitations. Recent advancements in
      robotic technology have generated the possibility of incorporating advanced
      technological tools to the neurosurgical operating room. Although previous
      studies have addressed the specific details of new robotic systems, there is very
      little literature on the strengths and drawbacks of past attempts, currently
      available platforms and prototypes in development. In this review, the authors
      present a critical historical analysis of the development of robotic technology
      in neurosurgery as well as a comprehensive summary of the currently available
      systems that can be expected to be incorporated to the neurosurgical
      armamentarium in the near future. Finally, the authors present a critical
      analysis of the main technical challenges in robotic technology development at
      the present time (such as the design of improved systems for haptic feedback and
      the necessity of incorporating intraoperative imaging data) as well as the
      benefits which robotic technology is expected to bring to specific neurosurgical
      subspecialties in the near future. 

PMID- 24729138
TI  - Optical coherence tomography characteristics of the iris in Cogan-Reese syndrome.
AB  - PURPOSE: To describe the characteristic optical coherence tomography (OCT)
      findings of the iris in Cogan-Reese syndrome. METHODS: A 63-year-old woman was
      referred for consultation due to diffuse pigmentation of the iris and elevated
      intraocular pressure (IOP) in the left eye. The clinical examination revealed
      Cogan-Reese syndrome with pedunculated iris outcroppings on the entire iris
      surface, and no peripheral anterior synechia. The right eye was normal with
      normal IOP. RESULTS: Imaging the left iris with the CAM-L cornea lens adapter of
      the Optovue Fourier-domain OCT (RTVue-OCT) showed a folded iris surface, an
      increased total iris thickness, and an increased distance between the anterior
      and posterior iris layers, compared to those of the healthy right eye.
      CONCLUSIONS: Traction by the pathological endothelial cell layer that covers the
      iris surface in Cogan-Reese syndrome causes characteristic OCT signs in the iris.
      Detection of the folded iris surface, increase of iris thickness, and increase of
      the distance between the anterior and posterior iris layers with RTVue-OCT
      anterior segment examination may promote the correct diagnosis and may help the
      clinician to discriminate Cogan-Reese syndrome from true iris nevi or iris
      melanoma.

PMID- 24729139
TI  - Comparison of intralesional corticosteroid and propranolol treatment of
      periorbital infantile hemangiomas: an outcome study of 61 cases.
AB  - PURPOSE: To compare intralesional corticosteroid (IC) injections with oral
      propranolol in children with periorbital infantile hemangioma (IH). METHODS:
      Children were diagnosed with IH and treated with IC (n = 29) or propranolol (n =
      14). In cases in which no further improvement was seen, treatment was stopped and
      the outcome measured. Type, duration, and complications of treatment and
      supportive or additional therapies were scored, along with outcomes of visual
      measurements, at the start and end of therapy. RESULTS: Twenty-one of the 29
      children (72%) treated with IC injections were given a second injection and 16
      (55%) were given more than two. Median duration of IC therapy was 15.9 months
      (interquartile range (IQR) 10.28), compared with 6.5 months (IQR 4.87) for
      propranolol (p<0.001). The complications reported after IC injections were
      bleeding (n = 9) and ulceration (n = 7). No complications were noted in the
      propranolol group. Additional therapy consisting of oral prednisolone therapy was
      applied in one child from the steroid-treated group. The levels of amblyopia and
      the median absolute improvement did not significantly differ between the groups.
      CONCLUSIONS: The IC injections and oral propranolol medication equally improved
      amblyopia in children with IH of the periorbital and cheek region; however,
      propranolol was associated with fewer complications and additional or supportive
      treatment was not indicated. We prefer oral propranolol medication over IC
      injections in cases in which IH threatens to hamper visual acuity.

PMID- 24729140
TI  - Aggressive skull base metastasis from uveal melanoma: a clinicopathologic study.
AB  - PURPOSE: We present the clinical, pathologic, and genetic findings of the first
      reported case of choroidal melanoma that developed a late recurrence and
      aggressive metastasis to the skull base without evidence of hepatic involvement.
      METHODS: Retrospective chart review and clinicopathologic correlation of ocular
      and brain tissue, including sequencing of BAP1 for mutations. RESULTS: A 55-year
      old woman was diagnosed with choroidal melanoma and treated with proton
      radiotherapy. Six years later, she developed a rapidly growing local recurrence
      involving the ciliary body and iris. Upon enucleation, histopathology revealed an
      iris and ciliary body epithelioid melanoma that was contiguous with the
      previously treated, regressed spindle cell choroidal melanoma. Imaging was
      initially negative for brain involvement. Two months later, she developed cranial
      neuropathies and was found to have a large skull base lesion that required
      surgical debulking for pain palliation. Histopathology confirmed the lesion to be
      metastatic melanoma. Both ocular and brain tumor specimens were wild-type for
      BAP1. Throughout her course, she developed no hepatic metastases. CONCLUSIONS:
      Uveal melanoma may metastasize to the skull base. The present case was
      characterized by delayed onset and unusual aggressiveness of the metastatic
      disease, and lack of BAP1 mutation. The unusual course highlights a unique
      phenotype that may reflect an alternate molecular mechanism for metastatic
      disease.

PMID- 24729141
TI  - Donor Descemet-off versus Descemet-on deep anterior lamellar keratoplasty: a
      confocal scan study.
AB  - PURPOSE: To compare confocal features of grafts following deep anterior lamellar
      keratoplasty (DALK) using a donor without Descemet membrane (DM) versus a full
      thickness donor with intact DM and endothelium. METHODS: This retrospective
      comparative study examined 45 eyes from patients with keratoconus who underwent
      DALK using the big-bubble technique. The big-bubble technique yielded a bared DM
      in all keratoconic eyes. Twenty-seven eyes received tissue from a donor without
      DM (group 1), while 18 received tissue from a full-thickness donor with an intact
      DM and endothelium (group 2). A group of normal eyes (n = 28, group 3) served as
      controls. Confocal microscopy was used to determine keratocyte density, explore
      the donor-recipient interface including clarity and reflectivity, evaluate
      endothelial cell density and morphology, as well as measure interface depth and
      central corneal thickness. RESULTS: Mean follow-up duration was 20.2 +/- 8.6
      months and 29.6 +/- 17.0 months in groups 1 and 2, respectively (p = 0.13).
      Confocal scan demonstrated that the keratocyte profiles and distribution were
      more similar to normal corneas in group 2. Significantly more severe interface
      haziness was observed when donor DM and endothelium was retained (mean interface
      reflectivity value of 102.7 +/- 22.1 versus 161.7 +/- 30.0 light reflectance
      units in groups 1 and 2, respectively, p<0.001). CONCLUSIONS: Graft cellular
      profiles and healing response at the donor-recipient interface can be profoundly
      affected depending on whether donor DM and endothelium is removed or retained.

PMID- 24729142
TI  - Scleral shield: primary results of a new surgical technique in augmenting porous
      orbital implant protection.
AB  - PURPOSE: To evaluate the value of using an additional scleral shield in providing
      further protection of inserted Medpor(r) implants in eviscerated globes. METHODS:
      This was a prospective interventional case series that included 30 patients with
      blind and/or disfiguring globe that warranted evisceration. Cases with
      intraocular masses, retained intraocular foreign bodies, as well as secondary
      ball implantation were excluded. All patients underwent regular evisceration with
      porous polyethylene ball (Medpor(r)) implantation. The sutured wound was further
      covered by scleral patch graft followed by closure of Tenon capsule and
      conjunctiva in separate layers. Patients were evaluated for implant exposure and
      all of them completed at least 4 years of follow-up. RESULTS: The study involved
      26 male and 4 female participants with age ranging from 16 to 65 years (mean
      40.74 +/- 15.86 years). The Medpor sizes varied from 16 to 22 mm in diameter. It
      is a simple extra step with no reported exposure, infection, or granulomas during
      the 4 years of follow-up. CONCLUSIONS: Scleral shield is a simple surgical
      technique that provides an extra layer of autogenous tissue to cover inserted
      orbital implant following evisceration with promising results in preventing their
      exposure.

PMID- 24729143
TI  - Choroidal thinning in pseudoexfoliation syndrome detected by enhanced depth
      imaging optical coherence tomography.
AB  - PURPOSE: To measure choroidal thickness in patients with pseudoexfoliation (PEX)
      syndrome and to compare the values with control eyes using enhanced depth imaging
      optical coherence tomography (EDI-OCT). METHODS: Thirty-four patients with PEX
      syndrome and 30 age- and sex-matched healthy subjects were included in this
      study. Only one eye of each of the patients was included. Choroidal thickness was
      measured manually from the outer border of the retinal pigment epithelium to the
      inner scleral border at the subfovea, 3 mm temporal to the fovea, and 3 mm nasal
      to the fovea using EDI-OCT. RESULTS: A total of 34 eyes from 34 consecutive
      patients with PEX syndrome (19 women and 15 men; mean age 75.3 +/- 6.6 years)
      were included in the analysis. The mean subfoveal, temporal, and nasal choroidal
      thickness was significantly thinner in the PEX syndrome group compared with the
      control group (p<0.05, at all points). The mean choroidal thickness in the PEX
      syndrome group was as follows: 259 +/- 33 um, 211 +/- 29 um, and 106 +/- 24 um,
      subfoveal, temporal, and nasal to the fovea, respectively. In comparison, the
      mean choroidal thickness in the control group was 274 +/- 23 um, 225 +/- 17 um,
      and 117 +/- 17 um, at the subfovea, 3 mm temporal to the fovea, and nasal to the
      fovea, respectively. CONCLUSIONS: In PEX syndrome, there is choroidal thinning
      subfoveal, temporal, and nasal to the fovea on EDI-OCT. Decreased choroidal
      thickness, probably due to increased vascular resistance, and reduced blood flow,
      is seen in PEX syndrome.

PMID- 24729144
TI  - Management of recurrent corneal ulcers: use of amniotic membrane.
AB  - PURPOSE: Amniotic membrane (AM), or amnion, is a thin membrane on the inner side
      of the fetal placenta; it completely surrounds the embryo/fetus and delimits the
      amniotic cavity, which is filled by amniotic liquid. In recent years, the
      structure and function of the amnion have been investigated due to its
      pluripotent properties, which are an attractive source for tissue transplantation
      and reconstructive surgery. The pioneering use of AM in skin transplantation by
      Davis dates back to 1910; in 1913, Sabella and Stern employed it in the treatment
      of burns and superficial scars. Certain characteristics make the AM ideally
      suited to its application in ocular surface reconstruction. It can be easily
      obtained and its availability is nearly unlimited. We report a case of AM
      transplantation to treat ocular surface abnormality. METHODS: A 28-year-old man
      came to our attention for persistent foreign body feeling and pain in his right
      eye. Because of progressive clinical worsening, we decided to perform surgical
      apposition of AM. RESULTS: Clinical and instrumental follow-up was conducted with
      periodic complete checkups. At 1 year follow-up, best-corrected visual acuity was
      4/10. CONCLUSIONS: Characteristics of AM make it potentially useful to treat
      ocular surface abnormalities.

PMID- 24729145
TI  - Vascularization of conjunctival autografts in pterygium surgery: comparison of
      fibrin glue with sutures.
AB  - PURPOSE: To monitor the development of graft vascularization after pterygium
      excision with conjunctival autograft transplantation (CAT) using indocyanine
      green angiography (ICGA) and to compare the graft vascularization between 2
      different fixation techniques (fibrin glue and sutures). METHODS: A total of 26
      eyes of 26 patients with primary pterygium were randomly assigned after pterygium
      excision as having either fibrin glue (13 eyes) or Vicryl sutures (13 eyes) for
      CAT. Anterior segment ICGA findings were evaluated postoperatively at 1, 7, and
      15 days and the percentages of graft vascularization in both groups were compared
      using pixel analysis software program. RESULTS: The mean +/- SD age of patients
      in the suture and fibrin glue groups was 52.1 +/- 12.7 years and 57.1 +/- 9.82
      years, respectively. There was no statistically significant difference between
      the groups regarding age, sex, or follow-up (p<0.05 for all). Also, the mean
      intraoperative defect size was not significantly different between the groups,
      which was measured as 20.11 +/- 10.44 mm2 in the suture group and 23.44 +/- 12.34
      mm2 in the fibrin glue group (p = 0.343). The mean percentage of vascularized
      graft area at postoperative day 1 and 7 was 18.1 +/- 7.8% and 25.3 +/- 8.6% in
      the suture group and 34.8 +/- 10.2% and 66.1 +/- 17.8% in the fibrin glue group.
      The difference between the groups was statistically significant (p<0.01 for
      both). At postoperative day 15, all grafts were 100% perfused in both groups.
      CONCLUSIONS: Fibrin glue fixation of conjunctival autografts led to more
      vascularization in the early postoperative period than suture fixated grafts,
      which in turn may have significance in terms of graft health and pterygium
      recurrence.

PMID- 24729146
TI  - "Pushed" stent intubation for treatment of complex congenital nasolacrimal duct
      obstruction.
AB  - PURPOSE: To assess the success rate of pushed stent intubation in children with
      complex congenital nasolacrimal duct obstruction (CNLDO). METHODS: This
      prospective study was performed in a single academic center. Forty-four eyes with
      complex CNLDO were treated with pushed stent intubation. Outcome measures
      included clinical signs plus a parental history of residual symptoms at 6 months
      after surgery. Relative risk with 95% confidence intervals (CI) for outcomes was
      reported. RESULTS: The mean follow-up after surgery was 9.0 months (range 6.5-13
      months). Complete resolution was achieved in 26 of 44 eyes (59.1%; 95% CI 43.3%
      73.3%) after pushed stent. Sex (odds ratio [OR] 2.9; 95% CI 0.4-18.9), age (OR
      0.9; 95% CI 0.5-1.5), previous history of probing (OR 1.1; 95% CI 0.1-8.1), and
      presence of mucopurulent discharge (OR 1.1; 95% CI 0.1-7.8) did not have
      significant impact on the failure rate in all subjects. CONCLUSIONS: In patients
      with complex CNLDO, treatment with a pushed stent intubation alleviated the
      clinical signs and symptoms of CNLDO. Pushed stent has the advantage of reduced
      operating time and easy placement.

PMID- 24729147
TI  - The economic impact of nocturia.
AB  - Sleep disturbances associated with nocturia cause direct, indirect, and
      intangible costs. Direct costs are primarily associated with injuries from
      falling. Indirect costs are associated with loss of work productivity. Intangible
      costs include emotional distress, behavioral modifications, feelings of loss of
      control, poor mood, and cancellation of planned activities. A study that compared
      the number of falls for patients with varying numbers of voids per night
      demonstrated that the incremental risk (population attributable risk [PAR]) of
      falling as a result of nocturia (>= 2 voids compared with <= 1 void) was 16.2%.
      Using the 16.2% PAR, the annual direct cost of nocturia in the USA was estimated
      at $1.5 billion. An analysis in the EU-15 countries estimated the total annual
      cost of hospitalizations for hip fracture due to severe nocturia to be
      approximately ? 1 billion. Studies have shown that periods of sick leave are
      significantly greater in both men and women who have more nocturnal voids, with
      an estimated annual indirect cost of nocturia of $61 billion in the USA. A
      similar European analysis showed an estimated annual cost of lost work
      productivity due to nocturia of ? 29 billion in the EU-15. The intangible
      personal costs of nocturia are related to diminished quality of life and overall
      health status. High-quality articles on the cost of illness associated with
      nocturia, as well as cost-benefit analyses of nocturia treatment, are generally
      lacking.

PMID- 24729148
TI  - Impact of nocturia on sleep and quality of life: a brief, selected review for the
      International Consultation on Incontinence Research Society (ICI-RS) nocturia
      think tank.
AB  - Nocturia, the need to awaken at night to void, is a highly prevalent disorder
      that negatively affects nocturnal sleep, increases daytime tiredness, and
      adversely impacts quality of life. In this selective review, we provide the
      reader an overview of current work in this area. From the perspective of
      disturbed sleep, two divergent perspectives have emerged from the literature when
      discussing nocturia. The first is that a patient awakens because of an urge to
      urinate. The second is that a patient awakens during the night for some reason
      unrelated to urinary urge (e.g., an awakening from an environmental source or
      from intrinsic lightening of sleep) and then decides to void while awake. In the
      few studies that have inquired about nocturia as a cause of awakenings, nocturia
      often ranks above the traditional psychological or physical factors. Not only is
      nocturia likely to disrupt sleep, but it may impact waking quality of life as
      well. A number of generic and nocturia-related questionnaires have been used to
      quantify the effect of nocturia on quality of life. In this short paper, we
      introduce the reader to several key studies in these important areas.

PMID- 24729149
TI  - Management of nocturia: the role of antidiuretic pharmacotherapy.
AB  - Strategies to manage nocturia include lifestyle modifications and treatment with
      alpha-blockers, antimuscarinic therapies, and antidiuretics. The concept of
      achieving success should not be limited to reduction of nighttime voids; it
      should ideally include proof of improvement of conditions generally associated
      with nocturia, such as falls, quality of life, and overall health. Few studies
      have looked specifically at parameters other than nocturnal voids, such as sleep
      latency, first undisturbed sleep period (FUSP), and total sleep time, including
      their clinical relevance to patient well-being. Lifestyle modifications, such as
      voiding before bedtime, limiting caffeine and alcohol, and adjusting medication
      timing, may be initially effective in mild cases of nocturia. Statistically
      significant reductions in voiding have been reported with antimuscarinic agents
      and alpha-blockers as initial therapy, but these reductions generally are not
      clinically relevant. The antidiuretic therapy desmopressin acetate, a selective
      vasopressin receptor 2 agonist, is effective in adults with nocturia associated
      with nocturnal polyuria; however, hyponatremia can occur. The newest formulation
      desmopressin orally disintegrating sublingual tablet (ODST)--has greater
      bioavailability; thus, lower doses can be used, potentially reducing hyponatremia
      risk. A phase 3 study demonstrated statistically significant reductions in
      nocturnal voids for desmopressin ODST 50 and 100 ug versus placebo (-1.18 and 
      1.43 vs. -0.86; P = 0.02 and P < 0.0001, respectively) in patients with nocturia.
      Treatment was well-tolerated, and low-dose desmopressin ODST was associated with
      statistically significant increases in duration of FUSP. Development of a
      validated composite endpoint may help clinicians identify and compare strategies
      for treating nocturia.

PMID- 24729150
TI  - Terminology, epidemiology, etiology, and pathophysiology of nocturia.
AB  - Nocturia, awaking from sleep to void, has a negative impact on health and well
      being. Nocturia affects men and women and is more prevalent among the elderly.
      More than two nocturnal voids is considered to be a clinically meaningful
      threshold associated with significant negative outcomes for health and well
      being, and the timing of awakening has a significant bearing on the negative
      consequences of nocturia. Several serious underlying pathophysiologic conditions
      may be associated with nocturia. A thorough history and assessment of number and
      times of voids, void volume, and fluid intake is essential for determining the
      etiology of a patient's nocturia. With data obtained from the frequency-volume
      chart (FVC), which is used to collect quantitative voiding data, a patient's
      nocturia may be classified as global polyuria, nocturnal polyuria, reduced
      bladder capacity, or a combination of these categories. Global polyuria is
      defined as 24-hr urinary output that exceeds 40 ml/kg body weight and results in
      increased 24-hr urinary frequency. Nocturnal polyuria is defined as more than 20%
      of daily urine output at night in young patients and more than 33% in elderly
      patients. Reduced bladder capacity may be a result of idiopathic or neurogenic
      detrusor overactivity, bladder outlet obstruction, or reduced nocturnal bladder
      capacity. The pathophysiology underlying the findings of the FVC falls into five
      main categories: global polyuria, nocturnal polyuria, reduced bladder capacity,
      sleep disorders, and circadian clock disorders. This review discusses the
      epidemiology, etiology, and pathophysiology of nocturia.

PMID- 24729151
TI  - Renal physiology of nocturia.
AB  - Renal function, diurnal fluctuations in arginine vasopressin (AVP) secretion,
      sex, and advanced age affect urine formation and may contribute to nocturia.
      Renal effects of AVP are mediated by AVP V2 receptors in the kidney collecting
      duct. Changes in AVP concentration have the greatest relative effects on urine
      volume when AVP levels are low; therefore small changes can have a large effect
      on renal water excretion. AVP is the major regulator of water excretion by the
      kidneys, and AVP levels have been shown to affect nocturnal voiding. Results of
      several studies show that patients with nocturia had no significant variation in
      plasma AVP, whereas patients without nocturia had significant diurnal variation
      in plasma AVP. The V2 receptor gene is located on the X chromosome, which has
      important sex-specific consequences. For example, mutations in the V2 gene can
      cause nephrogenic diabetes insipidus, predominantly in men. Age-related changes
      in water metabolism are associated with overall body composition, kidney, and
      brain. Older people generally experience decreased extracellular fluid and plasma
      volume, which leads to increased adverse consequences from net body water gain or
      loss. Renal function declines with age, and the ability to concentrate urine and
      conserve sodium is reduced in the elderly. Thirst perception is also decreased in
      the elderly, who, compared with younger people, tend to hypersecrete AVP in
      response to higher plasma osmolality, possibly resulting in hyponatremia. These
      aspects of renal physiology should be considered when antidiuretic drugs are
      prescribed for the treatment of nocturia.

PMID- 24729152
TI  - All-cause mortality as an outcome in epidemiologic studies: proceed with caution.

PMID- 24729153
TI  - Diagnosis and treatment of snoring in adults-S2k Guideline of the German Society
      of Otorhinolaryngology, Head and Neck Surgery.
AB  - OBJECTIVES: This guideline aims to promote high-quality care by medical
      specialists for subjects who snore and is designed for everyone involved in the
      diagnosis and treatment of snoring in an in- or outpatient setting. DISCUSSION:
      To date, a satisfactory definition of snoring is lacking. Snoring is caused by a
      vibration of soft tissue in the upper airway induced by respiration during sleep.
      It is triggered by relaxation of the upper airway dilator muscles that occurs
      during sleep. Multiple risk factors for snoring have been described and snoring
      is of multifactorial origin. The true incidence of snoring is not clear to date,
      as the incidence differs throughout literature. Snoring is more likely to appear
      in middle age, predominantly in males. Diagnostic measures should include a sleep
      medical history, preferably involving an interview with the bed partner, and may
      be completed with questionnaires. Clinical examination should include examination
      of the nose to evaluate the relevant structures for nasal breathing and may be
      completed with nasal endoscopy. Evaluation of the oropharynx, larynx, and
      hypopharynx should also be performed. Clinical assessment of the oral cavity
      should include the size of the tongue, the mucosa of the oral cavity, and the
      dental status. Furthermore, facial skeletal morphology should be evaluated. In
      select cases, technical diagnostic measures may be added. Further objective
      measures should be performed if the medical history and/or clinical examination
      suggest sleep-disordered breathing, if relevant comorbidities are present, and if
      the subject requests treatment for snoring. According to current knowledge,
      snoring is not associated with medical hazard, and generally, there is no medical
      indication for treatment. Weight reduction should be achieved in every overweight
      subject who snores. In snorers who snore only in the supine position, positional
      treatment can be considered. In suitable cases, snoring can be treated
      successfully with intraoral devices. Minimally invasive surgery of the soft
      palate can be considered as long as the individual anatomy appears suitable.
      Treatment selection should be based on individual anatomic findings. After a
      therapeutic intervention, follow-up visits should take place after an appropriate
      time frame to assess treatment success and to potentially indicate further
      intervention.

PMID- 24729155
TI  - A systematic review of the quality of randomized controlled trials in head and
      neck oncology surgery.
AB  - OBJECTIVES/HYPOTHESIS: To determine the quality of randomized controlled trials
      (RCTs) in head and neck surgery in which surgery was a primary intervention. DATA
      SOURCES: Potential articles were identified in PubMed without publication date
      restrictions. REVIEW METHODS: Articles were scored using the CONSORT checklist
      and the relationship between the checklist score and whether the first and/or
      last authors were surgeons was investigated. Differences in the checklist score
      based on how many surgeons were among the first and last authors of the study
      were analyzed using the Kruskal-Wallis test. Fisher's exact test was used to
      examine if there was a significant difference of the reporting of individual
      items from the checklist between surgeons and nonsurgeons. A nonparametric trend
      test was used to determine whether there was a difference in the reporting of
      individual items based on whether there were none, one, or two surgeons among
      first and last authors. RESULTS: A total of 38 publications satisfied the
      inclusion criteria. There was a trend toward lower quality for studies in which
      surgeons were either first, last, or both first and last authors compared to
      studies that were first-authored and last-authored by nonsurgeons (P = 0.068).
      Nonsurgeons were more likely to report on critical elements regarding hypothesis,
      sample size determination, randomization, and eligibility of centers (P = 0.023
      0.058). CONCLUSION: The quality of RCTs in head and neck surgery is poor.
      Improved training in conducting and reporting clinical research is needed in
      otolaryngology residencies.

PMID- 24729156
TI  - Private sector involvement and competition have not improved healthcare in
      England, report shows.

PMID- 24729157
TI  - The SGLT2 Inhibitor Empagliflozin for the Treatment of Type 2 Diabetes Mellitus:
      a Bench to Bedside Review.
AB  - INTRODUCTION: The treatment of type 2 diabetes mellitus (T2DM) continues to pose
      challenges for clinicians and patients. The dramatic rise in T2DM prevalence,
      which has paralleled the rise in obesity, has strained the healthcare system and
      prompted the search for therapies that not only effectively treat hyperglycemia,
      but are also weight neutral or promote weight loss. In most clinical situations
      after diagnosis, patients are advised to adopt lifestyle changes and metformin is
      initiated to help control blood glucose levels. However, metformin may not be
      tolerated, or may not be sufficient for those with higher glucose levels at
      diagnosis. Even among those who have initial success with metformin, the majority
      eventually require one or more additional agents to achieve their treatment
      goals. Because T2DM is a progressive disease, the requirement for combination
      treatment escalates over time, driving the need for therapies with complementary
      mechanisms of action. METHODS AND RESULTS: Online public resources were searched
      using "empagliflozin", identifying 32 articles in PubMed, and 12 abstracts
      presented at the 2013 American Diabetes Association meeting. Peer-reviewed
      articles and abstracts describing preclinical studies and clinical trials were
      retrieved, and relevant publications included in this review. Trials registered
      on clinicaltrials.gov were searched for ongoing empagliflozin studies.
      CONCLUSION: The sodium-glucose co-transporter 2 (SGLT2) inhibitors are of great
      interest since they provide a novel, insulin-independent mechanism of action. The
      SGLT2 inhibitor empagliflozin has demonstrated promising pharmacodynamic and
      pharmacokinetic properties. In clinical trials, empagliflozin has demonstrated a
      good efficacy and safety profile in a broad range of patients with T2DM, and
      appears to be an attractive adjunct therapeutic option for the treatment of T2DM.
      Ongoing trials, including patients with T2DM and comorbidities such as
      hypertension, are expected to provide important additional data, which will
      further define the role of empagliflozin in a growing movement toward
      individualized approaches to diabetes care.

PMID- 24729158
TI  - Use of Vildagliptin in Management of Type 2 Diabetes: Effectiveness, Treatment
      Persistence and Safety from the 2-Year Real-Life VILDA Study.
AB  - INTRODUCTION: There is an increasing interest for real-life data on drug use in
      many countries. Reimbursement authorities more and more request observational
      studies to assess the conditions of use of the products but also to improve
      knowledge about efficacy and safety in the real world and on a longer term than
      in clinical trials. AIM: To evaluate the effectiveness, treatment persistence and
      tolerability of vildagliptin in clinical practice. METHODS: This observational, 2
      year prospective cohort study was conducted in France on request of the Health
      Authorities [Haute Autorite de Sante (HAS)]. Type 2 diabetic mellitus (T2DM)
      patients initiating vildagliptin (including the fixed combination vildagliptin
      metformin) or treated for <6 months were recruited through a national
      representative sample of general practitioners (GPs) (n = 482) and diabetologists
      (n = 84) between March 2010 and December 2011. At inclusion and each follow-up
      visit at ~ 6, 12, 18 and 24 months, a questionnaire was completed by the
      physician collecting information on socio-demographic, clinical and biological
      data, treatments and adverse events. RESULTS: 1,700 patients were included: 60%
      were males, aged 63 +/- 11 years, with diabetes duration 7 +/- 6 years and body
      mass index (BMI) 30 +/- 6 kg/m(2). 45% were obese, 70% treated for hypertension
      and 66% for dyslipidemia. 64% of the patients received vildagliptin in dual
      therapy with metformin. 82% of patients completed the 2-year follow-up.
      Glycosylated hemoglobin (HbA1c) decreased from a mean baseline of 7.8 +/- 1.2%
      when vildagliptin was started, to 7.0 +/- 1.1% at 6 months and remained stable
      thereafter over 2 years. Mean weight, glomerular filtration rate, liver enzymes,
      and lipid parameters were unchanged over the study period. Eight patients (0.5%),
      all concomitantly treated with insulin and/or sulphonylureas, reported one severe
      hypoglycemia and 47 (2.9%) patients reported 64 non-severe symptomatic
      hypoglycemia (59% occurred when patients were treated with insulin and/or
      sulphonylureas). At 6 months, 44.9% of vildagliptin-treated patients reached an
      HbA1c <7% without hypoglycemia and no weight gain, and this percentage increased
      to 49.7% at 24 months. Vildagliptin treatment maintenance at 2 years was 88.8%
      [95% CI (87.2%; 90.4%)], with 4% of patients discontinuing for adverse events.
      CONCLUSIONS: In everyday conditions of care, vildagliptin efficacy was in line
      with existing data from randomized clinical trials, sustained over 2 years, with
      low discontinuation rate and low hypoglycemia risk.

PMID- 24729159
TI  - EYA1 expression in gastric carcinoma and its association with clinicopathological
      characteristics: a pilot study.
AB  - As the second most frequent cause of cancer death, gastric cancer is a common
      disease worldwide. Most of the patients are being diagnosed in the stage that
      conventional treatments are not effective, and invasion and metastases lead to
      death. So, identification of novel molecular markers to improve early diagnosis,
      prognosis and treatment of the gastric cancer is a necessity. EYA1 is a member of
      EYA family which their deregulation has been demonstrated in several types of
      cancer. The aim of this study was to assess EYA1 gene expression in tissues of
      the gastric cancer patients and to investigate its correlation with
      clinicopathological parameters. A total of 60 tumor and non-tumor gastric
      specimens were evaluated for EYA1 gene expression using quantitative real-time
      PCR. The EYA1 expression decreased significantly in gastric tumor tissues
      compared with adjacent normal tissues. We further showed that there was a
      negative correlation between the EYA1 gene expression levels, tumor size,
      lymphatic invasion and distant metastasis. In conclusion, EYA1 might be used as a
      potential biomarker for monitoring gastric carcinoma progression rate. Further
      studies to determine the mechanism of action of EYA1 is needed to unravel the
      role of this gene in gastric cancer pathogenesis. 

PMID- 24729160
TI  - On the status of beta-cell dysfunction and insulin resistance of breast cancer
      patient without history of diabetes after systemic treatment.
AB  - To estimate the status of beta-cell dysfunction and insulin resistance of breast
      cancer (BC) patient without history of diabetes mellitus (DM) after systemic
      treatment through an oral glucose tolerance test (OGTT) and insulin releasing
      test (IRT). All the 128 BC patients without history of DM after systemic
      treatment underwent OGTT and IRT test. Fasting and 2-h glucose levels were
      measured to confirm undiagnosed DM and prediabetes. Insulin sensitivity was
      estimated by homeostasis model assessment of insulin resistance (HOMA-IR) and
      Matsuda index and disposition index (IGI/HOMA-IR). Insulin secretion was
      estimated by the insulinogenic index (IGI) [Delta insulin/Delta glucose (30-0
      min)]. Insulin concentrations during the OGTT and IRT at baseline were used to
      derive the patterns of insulin secretion curve (pattern 1, pattern 2, pattern 3,
      pattern 4 and pattern 5), which were used to estimate the risk of developing DM.
      Of 128 BC patients without history of DM after systemic treatment, there were 46
      cases (35.9%) of NGT, 60 cases (46.9%) of prediabetes and 22 cases (17.2%) of DM.
      The BMI of prediabetes and DM were higher than NGT groups with statistical
      significance. After adjusted for BMI, IGI was significantly lower in DM group but
      not significantly different between NGT group and prediabetes group. HOMA-IR,
      Matsuda index and disposition index were significantly different in DM group
      compared with NGT group and prediabetes and also significantly different between
      NGT and prediabetes groups. The total rates of patterns 4 and 5 in NGT and
      prediabetes groups were 15.3% (10.9 and 4.4%) and 48.3% (31.6 and 16.7%),
      respectively. beta-Cell dysfunction and insulin resistance may appear in BC
      patients after systemic treatment. BC patients have high risk in development of
      DM even in NGT and prediabetes groups confirmed by OGTT.

PMID- 24729154
TI  - Developmental and contextual considerations for adrenal and gonadal hormone
      functioning during adolescence: Implications for adolescent mental health.
AB  - Substantial research has implicated the hypothalamic-pituitary-adrenal (HPA) and
      hypothalamic-pituitary-gonadal (HPG) axes independently in adolescent mental
      health problems, though this literature remains largely inconclusive. Given the
      cross-talk between the HPA and HPG axes and their increased activation in
      adolescence, a dual-axis approach that examines both axes simultaneously is
      proposed to predict the emergence and persistence of adolescent mental health
      problems. After briefly orienting readers to HPA and HPG axis functioning, we
      review the literature examining associations between hormone levels and changes
      with behavior during adolescence. Then, we provide a review of the literature
      supporting examination of both axes simultaneously and present the limited
      research that has taken a dual-axis approach. We propose future directions
      including consideration of between-person and within-person approaches to address
      questions of correlated changes in HPA and HPG hormones. Potential moderators are
      considered to increase understanding of the nuanced hormone-behavior associations
      during key developmental transitions.

PMID- 24729161
TI  - Facile synthesis of brush poly(phosphoamidate)s via one-pot tandem ring-opening
      metathesis polymerization and atom transfer radical polymerization.
AB  - Poly(2-(dimethylamino)ethyl methacrylate) (PDMAEMA)-based brush
      poly(phosphoamidate)s are successfully synthesized by a combination of ring
      opening metathesis polymerization (ROMP) and atom transfer radical polymerization
      (ATRP) following either a commutative two-step procedure or a straightforward one
      pot process using Grubbs ruthenium-based catalysts for tandem catalysis. Compared
      with the traditional polymerization method, combining ROMP and ATRP in a one-pot
      process allows the preparation of brush copolymers characterized by a relatively
      moderate molecular weight distribution and quantitative conversion of monomer.
      Moreover, the surface morphologies and aggregation behaviors of these polymers
      are studied by AFM and TEM measurements. 

PMID- 24729166
TI  - METMAVI-VIth International Workshop on Spatio-Temporal Modelling.

PMID- 24729171
TI  - Snapshot of antidepressants at work: the structure of neurotransmitter
      transporter proteins.
AB  - In the sweet spot: Cocrystal structures of engineered neurotransmitter
      transporters reveal the binding mode of commonly prescribed antidepressants,
      providing a basis for a rational drug design for this class of proteins. The
      picture shows the structure of the dopamine transporter of Drosophila
      melanogaster in complex with the antidepressant nortriptyline. 

PMID- 24729172
TI  - The Richness of Task-Evoked Hemodynamic Responses Defines a Pseudohierarchy of
      Functionally Meaningful Brain Networks.
AB  - Functional magnetic resonance imaging can measure distributed and subtle
      variations in brain responses associated with task performance. However, it is
      unclear whether the rich variety of responses observed across the brain is
      functionally meaningful and consistent across individuals. Here, we used a
      multivariate clustering approach that grouped brain regions into clusters based
      on the similarity of their task-evoked temporal responses at the individual
      level, and then established the spatial consistency of these individual clusters
      at the group level. We observed a stable pseudohierarchy of task-evoked networks
      in the context of a delayed sequential motor task, where the fractionation of
      networks was driven by a gradient of involvement in motor sequence preparation
      versus execution. In line with theories about higher-level cognitive functioning,
      this gradient evolved in a rostro-caudal manner in the frontal lobe. In addition,
      parcellations in the cerebellum and basal ganglia matched with known anatomical
      territories and fiber pathways with the cerebral cortex. These findings
      demonstrate that subtle variations in brain responses associated with task
      performance are systematic enough across subjects to define a pseudohierarchy of
      task-evoked networks. Such networks capture meaningful functional features of
      brain organization as shaped by a given cognitive context. 

PMID- 24729175
TI  - Continuous self-healing life cycle in vascularized structural composites.

PMID- 24729173
TI  - Role of angiotensin modulation in primary headaches.
AB  - The renin-angiotensin system (RAS) is a major regulatory system controlling many
      different homeostatic mechanisms both within the brain and in the periphery.
      While it is primarily associated with blood pressure and salt/water regulation,
      increasing evidence points to the involvement of the RAS in both headache
      disorders specifically and pain regulation in general. Several publications have
      indicated that drugs blocking various elements of the renin-angiotensin system
      lead to a reduction in migraine. Additionally, interventions on different
      angiotensin peptides or their receptors have been shown to both reduce and
      increase pain in animal models. As such, modulation of the renin-angiotensin
      system is a promising approach to the treatment of headaches and other pain
      conditions. 

PMID- 24729176
TI  - Hydrogen sulfide delays nicotinamide-induced premature senescence via
      upregulation of SIRT1 in human umbilical vein endothelial cells.
AB  - The present study was designed to investigate the effect of hydrogen sulfide on
      cellular senescence of human umbilical vascular endothelial cells (HUVECs CC
      2517) and its underlying mechanism. The premature senescence-like phenotype
      HUVECs (the fourth passage) was induced by treatment with nicotinamide (NAM, an
      inhibitor of SIRT1, 5 mmol/L, 12 h). Cells were cultured with sodium hydrosulfide
      (NaHS, 12.5, 25, 50 and 100 MUmol/L) for 48 h in premature senescence-like
      phenotype HUVECs. The fourth passage of HUVECs was considered as young group.
      Senescence-associated (SA)-beta-galactosidase activities were detected to
      evaluate cell senescence, and the expression of SA heterochromatin foci (SAHF)
      was visualized by DAPI DNA staining. The mRNA and protein levels of SIRT1 were
      detected using RT-PCR and western blotting analysis, respectively. The results
      showed that beta-galactosidase positive cells and the formation of SAHF were
      markedly increased after treatment with NAM (5 mmol/L) for 12 h. We also found
      that NaHS (12.5 MUmol/L) had no effect on the percentage of SA beta-gal positive
      cells and the expression of SAHF, and the hallmarks decreased at the
      concentration of 25 and 50 MUmol/L, reaching the minimum at 50 MUmol/L, while the
      percentage of SA beta-gal positive cells and the expression of SAHF increased at
      the concentration of 100 MUmol/L. Furthermore, we found that both on protein and
      mRNA levels of SIRT1 in the Y+N+S50 group was significantly increased compared
      with that in Y+N group. In conclusion, NaHS delays senescence of HUVECs induced
      by NAM via upregulation of SIRT1 expression.

PMID- 24729177
TI  - A comparative study on mesozooplankton abundance and diversity between a
      protected and an unprotected coastal area of Andaman Islands.
AB  - The study was carried out to understand the variability in phytoplankton
      production (Chlorophyll a) and mesozooplankton diversity from two different
      shallow coastal regions of south Andaman viz. Port Blair Bay (PBB), the only real
      urban area among the islands and Mahatma Gandhi Marine National Park, a Marine
      Protected Area (MPA) at Wandoor. Seasonal sampling was carried out during the
      Northeast monsoon (NEM--November 2005), Intermonsoon (IM--April 2006), and
      Southwest monsoon (SWM--August 2006). Significant (P < 0.05) seasonal variation
      was observed in the environmental variables at both the regions. Higher average
      chlorophyll a (Chl. a) and mesozooplankton standing stock were observed at PBB
      compared to MPA, but the seasonal variation observed was marginal at both the
      study areas. Chl. a showed a steep increasing gradient from outer to the inner
      regions of the PBB. The number of zooplankton taxa recorded at both areas was
      quite similar, but marked differences were noticed in their relative contribution
      to the total abundance. Eventhough the Copepoda dominated at both the areas, the
      non-copepod taxa differed significantly between the regions. Dominance of
      carnivores such as siphonophores and chaetognaths were noticed at PBB, while
      filter feeders such as appendicularians and decapod larvae were more abundant at
      MPA. A total of 20 and 21 copepod families was recorded from PBB and MPA,
      respectively. Eleven species of chaetognaths were observed as common at both
      areas. Larval decapods were found to be predominant at MPA with 20 families;
      whereas, at PBB, only 12 families were recorded. In the light of the recent
      reports on various changes occurring in the coastal waters of the Andaman
      Islands, it is suspected that the difference in Chl. a as well as the
      mesozooplankton standing stock and community structure observed between the two
      study areas may be related to the various anthropogenic events influencing the
      coastal waters.

PMID- 24729178
TI  - Oak decline analyzed using intraannual radial growth indices, delta(13)C series
      and climate data from a rural hemiboreal landscape in southwesternmost Finland.
AB  - Decline of pedunculate oak (Quercus robur L.) was studied in SW Finland. This is
      a region where the species is growing near its northern distributional limit
      globally and a recent decline of mature trees has been described regionally. Tree
      rings of declining oaks were compared to the chronologies of healthy and oaks
      that died, climate series and stable isotope discrimination of carbon
      (delta(13)C) of comparable mature trees. The radial growth (earlywood, latewood,
      and annual ring width) of declining oaks was clearly deteriorated in comparison
      to healthy oaks, but recuperated, compared to oaks that died, through all index
      types. Comparison of climate relationships between growth and delta(13)C,
      expected to reflect oaks' intrinsic water use efficiency, indicated enhancing
      resistance to droughts through the growing season. The growth and the climatic
      growth response was differentiated in declining oaks as compared with the healthy
      and oaks that died revealing that: (1) declining oaks exhibited decreasing
      competitive strength as indicated by reduced overall growth relative to healthy
      oaks, (2) the growth of declining oaks was more sensitive to winter conditions,
      but less restricted by summer droughts than the growth of other oaks, and (3)
      healthy oaks were seen having benefitted from the ongoing lengthening of the
      growing season. Lack of correlativity between growth and delta(13)C became
      evident as their responses to temperature and precipitation variations deviated
      drastically during the other but summer months. Our results indicate that several
      different ecological factors, rather than a single climatic factor (e.g.,
      drought), are controlling the oak decline in the studied environment. 

PMID- 24729179
TI  - Lichens as a useful mapping tool?--an approach to assess atmospheric N loads in
      Germany by total N content and stable isotope signature.
AB  - To assess whether nitrogen (N) content and delta(15)N ratios in nitrophytic
      lichen species (Xanthoria parietina (L.) Th. Fr. (1860) and Physcia spp.
      (Schreb.) Michaux (1803)) reflect the quantity and quality of atmospheric N
      loads, 348 lichen samples from 174 sampling grid cells were investigated in the
      western part of Germany. The analysed lichen N content ranged between 0.98 and
      4.28 % and delta(15)N ratios between -15.2 and -1.3 0/00. Based on the N
      concentrations and the delta(15)N ratios of lichens, different landscape
      categories and coupled N deposition rates could be inferred for different regions
      of Germany. By analysing environmental variables like altitude, ammonia emission
      density, livestock unit and different defined deposition types, a direct
      relationship was found between lichen chemistry and N compounds produced from
      agricultural activity. The results support the development of a monitoring method
      which could be used nationally or even internationally to support current N
      deposition measurements, by providing reliable information on the quantity and
      quality of N deposition in high N environments. 

PMID- 24729180
TI  - The distribution and extent of heavy metal accumulation in song sparrows along
      Arizona's upper Santa Cruz River.
AB  - Heavy metals are persistent environmental contaminants, and transport of metals
      into the environment poses a threat to ecosystems, as plants and wildlife are
      susceptible to long-term exposure, bioaccumulation, and potential toxicity. We
      investigated the distribution and cascading extent of heavy metal accumulation in
      southwestern song sparrows (Melospiza melodia fallax), a resident riparian bird
      species that occurs along the US/Mexico border in Arizona's upper Santa Cruz
      River watershed. This study had three goals: (1) quantify the degree of heavy
      metal accumulation in sparrows and determine the distributional patterns among
      study sites, (2) compare concentrations of metals found in this study to those
      found in studies performed prior to a 2009 international wastewater facility
      upgrade, and (3) assess the condition of song sparrows among sites with differing
      potential levels of exposure. We examined five study sites along with a reference
      site that reflect different potential sources of contamination. Body mass
      residuals and leukocyte counts were used to assess sparrow condition. Birds at
      our study sites typically had higher metal concentrations than birds at the
      reference site. Copper, mercury, nickel, and selenium in song sparrows did exceed
      background levels, although most metals were below background concentrations
      determined from previous studies. Song sparrows generally showed lower heavy
      metal concentrations compared to studies conducted prior to the 2009 wastewater
      facility upgrade. We found no cascading effects as a result of metal exposure. 

PMID- 24729181
TI  - Assessing organic contaminant fluxes from contaminated sediments following dam
      removal in an urbanized river.
AB  - In this study, methods and approaches were developed and tested to assess changes
      in contaminant fluxes resulting from dam removal in a riverine system. Sediment
      traps and passive samplers were deployed to measure particulate and dissolved
      polycyclic aromatic hydrocarbons (PAHs) and polychlorinated biphenyls (PCBs) in
      the water column prior to and following removal of a small, low-head dam in the
      Pawtuxet River, an urbanized river located in Cranston, RI, USA. During the
      study, concentrations of particulate and dissolved PAHs ranged from 21.5 to 103
      MUg/g and from 68 to 164 ng/L, respectively. Overall, temporal trends of PAHs
      showed no increases in either dissolved or particulate phases following removal
      of the dam. Dissolved concentrations of PCBs were very low, remaining below 1.72
      ng/L at all sites. Particulate PCB concentrations across sites and time showed
      slightly greater variability, ranging from 80 to 469 ng/g, but with no indication
      that dam removal influenced any increases. Particulate PAHs and PCBs were sampled
      continuously at the site located below the dam and did not show sustained
      increases in concentration resulting from dam removal. The employment of passive
      sampling technology and sediment traps was highly effective in monitoring the
      concentrations and flux of contaminants moving through the river system.
      Variations in river flow had no effect on the concentration of contaminants in
      the dissolved or particulate phases, but did influence the flux rate of
      contaminants exiting the river. Overall, dam removal did not cause measurable
      sediment disturbance or increase the concentration or fluxes of dissolved or
      particulate PAHs and PCBs. This is due in large part to low volumes of impounded
      sediment residing above the dam and highly armored sediments in the river
      channel, which limited erosion. Results from this study will be used to improve
      methods and approaches that assess the short- and long-term impacts ecological
      restoration activities such as dam removal have on the release and transport of
      sediment-bound contaminants. 

PMID- 24729182
TI  - Estimation of spatial distrubition of groundwater level and risky areas of
      seawater intrusion on the coastal region in Carsamba Plain, Turkey, using
      different interpolation methods.
AB  - Groundwater level plays a significant role in coastal plains. Heavy pumping and
      excessive use of near-coast groundwater can increase the intrusion of seawater
      into the aquifers. In the present study, groundwater levels were measured at 59
      groundwater wells at different times during pre- and post-irrigation seasons
      (April and September of the year 2012) in Carsamba Plain, Turkey. To select the
      best method, two deterministic interpolation methods (inverse distance weighing
      (IDW) with the weights of 1, 2, and 3 and radial basis function (RBF) with spline
      with tension (SPT) and completely regularized spline (CRS)) and two stochastic
      methods (ordinary kriging (OK) with spherical, exponential, and Gaussian
      variograms) and cokriging (COK)) were compared and then the best interpolation
      method was used to evaluate the spatial distribution of groundwater levels in
      different seasons and seasonal changes. A total of nine different techniques were
      tested. Also, risky areas of seawater intrusion in coastal area were determined
      using the best methods for two periods. The performance of these interpolation
      methods is evaluated by using a validation test method. Statistical indices of
      correlation (R (2)), mean absolute error (MAE), and root-mean-square error (RMSE)
      were used to select and validate the best methods. Comparisons between predicted
      and observed values indicated RBF as the optimal method for groundwater level
      estimation in April and September. When the best method RBF and the worst method
      IDW were compared, significant differences were observed in the spatial
      distribution of groundwater. Results of the study also revealed that excessive
      groundwater withdrawals during the post-irrigation season dropped the groundwater
      levels up to 2.0 m in some sections. With regard to seawater intrusion, 9,103 ha
      of land area was determined to be highly risky and risky. 

PMID- 24729183
TI  - Editorial Comment: Re: Hanno, P., Malykhina, A. (2014) How are we going to make
      progress treating bladder pain syndrome? ICI-RS 2013. Neurourol Urodyn.

PMID- 24729184
TI  - Sulpiride versus placebo for schizophrenia.
AB  - BACKGROUND: Sulpiride is a relatively old antipsychotic drug reputed to have a
      low incidence of adverse effects and an effect on the negative symptoms of
      schizophrenia. This relatively inexpensive antipsychotic drug has a similar
      neuropharmacological profile to several novel atypical drugs. OBJECTIVES: To
      evaluate the effects of sulpiride for schizophrenia and other similar serious
      mental illnesses in comparison with placebo. SEARCH METHODS: We searched the
      Cochrane Schizophrenia Group Trials Register (September 2008) and references of
      all identified studies for further trial citations. We contacted pharmaceutical
      companies and authors of trials for additional information. We updated this
      search 7th November 2012. SELECTION CRITERIA: We included all randomised
      controlled trials (RCTs) comparing sulpiride with placebo for people with
      schizophrenia and other types of schizophrenia-like psychoses. The primary
      outcome of interest was clinically significant response in global state. DATA
      COLLECTION AND ANALYSIS: We independently inspected citations and abstracts,
      ordered papers, re-inspected and quality-assessed these. IMO and JW extracted
      data. We analysed dichotomous data using a random-effects risk ratio (RR) and
      estimated the 95% confidence interval (CI) around this. Where continuous data
      were included, we analysed these data using random-effects mean difference (MD)
      with a 95% CI. MAIN RESULTS: No new trials were included from the 2012 search.
      The review still includes two trials of short duration comparing sulpiride with
      placebo (total n = 113). No study reported our primary outcome of interest of
      'global state: clinically significant response', nor our secondary outcomes of
      interest of 'quality of life', 'severe adverse effects', and 'safety
      assessments'. As regards mental state, there were no clear differences between
      groups for either positive or negative symptoms; measured positive symptoms using
      the Manchester scale were skewed and therefore not included in meta-analysis (n =
      18, 1 RCT, very low quality evidence). Measured negative symptoms using the
      Manchester scale also demonstrated no clear difference (n = 18, 1 RCT, MD -3.0 CI
      -1.66 to 1.06, very low quality evidence). Few people left these studies by three
      months (n = 113, 2 RCTs, RR 1.00 CI 0.25 to 4.00). One subscore finding
      demonstrated a significant improvement in social behaviour using the Current
      Behaviour Schedule (CBS) when receiving placebo (n = 18, 1 RCT, MD -2.90 CI -5.60
      to -0.20). There were no data for many important outcomes such as global
      outcomes, service use or adverse effects. AUTHORS' CONCLUSIONS: Sulpiride may be
      an effective antipsychotic drug but evidence of its superiority over placebo from
      randomised trials is very limited. Practice will have to use evidence from
      sources other than trials until better evidence is generated.

PMID- 24729185
TI  - Incidence of second metachronous head and neck cancers: population-based outcomes
      over 25 years.
AB  - OBJECTIVES/HYPOTHESIS: The primary objective was to determine the incidence of
      second metachronous head and neck cancers (HNC) following an index HNC and
      estimate their overall survival. STUDY DESIGN: Retrospective cohort study.
      METHODS: A total of 1,658 consecutive primary HNC patients diagnosed in 1986 to
      1990 were identified through the prospectively maintained provincial BC Cancer
      Registry database. They were followed up for a period of 25 years. Survival
      analysis and second cancer estimates were performed with standard Kaplan-Meier &
      Cox regression analysis. RESULTS: Out of a total of 443 (27%) second cancers, 89
      (5%) second HNC occurred in 1,658 HNC patients, with an actuarial metachronous
      HNC incidence rate at 5, 10, 15, 20, and 25 years that was 3.9%, 8.1%, 10.4%,
      13.2%, and 14.5%, respectively. Second primary cancer (SPC) in lung and esophagus
      occurred in 155 (9%) and 32 (2%) patients, respectively. The median follow-up
      time for all patients and alive patients was 4.05 years (range, 0.2-25.0 years)
      and 23.2 years (range, 20.76-25.0 years), respectively. Of second HNC, 83 (93%)
      were metachronous. Oral cavity (P < 0.001) and oropharyngeal (P < 0.002) index
      cancers were more likely to develop a metachronous HNC. The overall survival rate
      for the metachronous HNC patients at 5 years is 15%. SPCs in esophagus and lung
      had lower overall survival compared to second HNC (P < 0.001). CONCLUSION: Oral
      cavity and oropharyngeal cancers carry the highest risk of a subsequent
      metachronous HNC. Given the incidence and prognosis of second HNC, future
      research should address the frequency and duration of screening the head and neck
      region for a second cancer.

PMID- 24729186
TI  - Circulating levels of soluble Fas ligand reflect disease progression in multiple
      myeloma.
AB  - Multiple myeloma (MM) plasma cells are apoptosis resistant. The system of Fas
      with its ligand (Fas-L) participates actively in the extrinsic apoptotic system.
      In oncology, its role is controversial, since it has been reported both to
      suppress and promote tumor growth. The aim of this study was to measure serum
      levels of soluble Fas-L (sFas-L) in patients with active MM and to correlate them
      with markers of disease activity. We studied 57 patients with active MM, along
      with 22 healthy controls. We measured serum levels of sFas-L and interleukin-6
      (IL-6) by enzyme-linked immunosorbent assays, as well of beta-2 microglobulin
      (B2M), C-reactive protein (CRP) and lactate dehydrogenase (LDH). We also measured
      the degree of bone marrow infiltration. All parameters were increased in
      patients, compared with controls (p < 0.001 for all cases) and also in parallel
      with disease stage (p < 0.001 for all cases). Positive correlations were noted
      between serum levels of sFas-L with IL-6, infiltration (p < 0.001 for both cases)
      and LDH (p < 0.04), but not with CRP and B2M. We suggest that the system of
      Fas/Fas-L participates actively in MM progression in a complex manner and that
      serum levels of sFas-L may reflect disease progression. Further studies are
      needed to determine its usefulness as a marker of disease activity.

PMID- 24729187
TI  - Rapid hybridization of chitosan-gold-antibodies via metal-free click in water
      based systems: a model approach for naked-eye detectable antigen sensors.
AB  - A surface plasmon resonance (SPR) expression after hybridization of chitosan-gold
      nanoparticle-antibody (CS-AuNPs-Ab) based on: i) metal-free click chemistry, and,
      ii) in water system as an approach for a rapid antigen sensing, is proposed. The
      chitosan-hydroxybenzyl triazole complex enables us to carry out the conjugation
      of mPEG and trifluoromethylated oxanorbornadiene (OND) in water. CS-mPEG-OND
      further allows metal-free click to hybridize chitosan (CS) with azido-modified
      gold nanoparticles (azido-AuNPs) in aqueous solution at room temperature. The CS
      mPEG-OND conjugated with LipL32 antibody (Ab) not only effectively binds with
      LipL32 antigen (Ag) but also performs the cycloaddition with azido-AuNPs to
      display a change in color within 2 min. The phenomenon leads to a simple and
      efficient naked-eye antigen detection technique. 

PMID- 24729188
TI  - Gas chromatographic detection of some nitro explosive compounds in soil samples
      after solid-phase microextraction with carbon ceramic copper nanoparticle fibers.
AB  - In this research, a new solid-phase microextraction fiber based on carbon ceramic
      composites with copper nanoparticles followed by gas chromatography with flame
      ionization detection was applied for the extraction and determination of some
      nitro explosive compounds in soil samples. The proposed method provides an
      overview of trends related to synthesis of solid-phase microextraction sorbents
      and their applications in preconcentration and determination of nitro explosives.
      The sorbents were prepared by mixing of copper nanoparticles with a ceramic
      composite produced by mixture of methyltrimethoxysilane, graphite, methanol, and
      hydrochloric acid. The prepared sorbents were coated on copper wires by dip
      coating method. The prepared nanocomposites were evaluated statistically and
      provided better limits of detection than the pure carbon ceramic. The limit of
      detection of the proposed method was 0.6 MUg/g with a linear response over the
      concentration range of 2-160 MUg/g and square of correlation coefficient >0.992.
      The new proposed fiber has been demonstrated to be a suitable, inexpensive, and
      sensitive candidate for extraction of nitro explosive compounds in contaminated
      soil samples. The constructed fiber can be used more than 100 times without the
      need for surface generation. 

PMID- 24729189
TI  - Nature-inspired nanoformulations for contrast-enhanced in vivo MR imaging of
      macrophages.
AB  - Magnetic resonance imaging (MRI) of macrophages in atherosclerosis requires the
      use of contrast-enhancing agents. Reconstituted lipoprotein particles that mimic
      native high-density lipoproteins (HDL) are a versatile delivery platform for Gd
      based contrast agents (GBCA) but require targeting moieties to direct the
      particles to macrophages. In this study, a naturally occurring methionine
      oxidation in the major HDL protein, apolipoprotein (apo) A-I, was exploited as a
      novel way to target HDL to macrophages. We also tested if fully functional GBCA
      HDL can be generated using synthetic apo A-I peptides. The fluorescence and MRI
      studies reveal that specific oxidation of apo A-I or its peptides increases the
      in vitro macrophage uptake of GBCA-HDL by 2-3 times. The in vivo imaging studies
      using an apo E-deficient mouse model of atherosclerosis and a 3.0 T MRI system
      demonstrate that this modification significantly improves atherosclerotic plaque
      detection using GBCA-HDL. At 24 h post-injection of 0.05 mmol Gd kg(-1) GBCA-HDL
      containing oxidized apo A-I or its peptides, the atherosclerotic wall/muscle
      normalized enhancement ratios were 90 and 120%, respectively, while those of GBCA
      HDL containing their unmodified counterparts were 35 and 45%, respectively.
      Confocal fluorescence microscopy confirms the accumulation of GBCA-HDL containing
      oxidized apo A-I or its peptides in intraplaque macrophages. Together, the
      results of this study confirm the hypothesis that specific oxidation of apo A-I
      targets GBCA-HDL to macrophages in vitro and in vivo. Furthermore, our
      observation that synthetic peptides can functionally replace the native apo A-I
      protein in HDL further encourages the development of these contrast agents for
      macrophage imaging.

PMID- 24729190
TI  - Effects of cations on protein and peptide charging in electrospray ionization
      from aqueous solutions.
AB  - The effects of eight different cations with ionic radii between 69 and 337 pm on
      the charging of peptides and proteins with electrospray ionization from aqueous
      acetate salt solutions are reported. Significant adduction occurs for all cations
      except NH4(+), and the average protein charge is lower when formed from solutions
      containing salts compared with solutions without salts added. Circular dichroism
      and ion mobility results show the protein conformations are different in pure
      water compared with salt solutions, which likely affects the extent of charging.
      The average charge of protein and peptide ions formed from solutions with Li(+)
      and Cs(+), which have Gibbs solvation free energies (GSFEs) that differ by 225
      kJ/mol, is similar. Lower charge states are typically formed from solutions with
      tetramethylammonium and tetraethylammonium that have lower GSFE values. Loss of
      the larger cations that have the lowest GSFEs is facile when adducted protein
      ions are collisionally activated, resulting in the formation of lower analyte
      charge states. This reaction pathway provides a route to produce abundant singly
      protonated protein ions under native mass spectrometry conditions. The average
      protein and peptide charge with NH4(+) is nearly the same as that with Rb(+) and
      K(+), cations with similar GSFE and ionic radii. This indicates that proton
      transfer from NH4(+) to proteins plays an insignificant role in the extent of
      protein charging in native mass spectrometry.

PMID- 24729191
TI  - Mass accuracy and isotopic abundance measurements for HR-MS instrumentation:
      capabilities for non-targeted analyses.
AB  - The development of automated non-targeted workflows for small molecule analyses
      is highly desirable in many areas of research and diagnostics. Sufficient mass
      and chromatographic resolution is necessary for the detectability of compounds
      and subsequent componentization and interpretation of ions. The mass accuracy and
      relative isotopic abundance are critical in correct molecular formulae generation
      for unknown compounds. While high-resolution instrumentation provides accurate
      mass information, sample complexity can greatly influence data quality and the
      measurement of compounds of interest. Two high-resolution instruments, an
      Orbitrap and a Q-TOF, were evaluated for mass accuracy and relative isotopic
      abundance with various concentrations of a standard mixture in four complex
      sample matrices. The overall average +/- standard deviation of the mass accuracy
      was 1.06 +/- 0.76 ppm and 1.62 +/- 1.88 ppm for the Orbitrap and the Q-TOF,
      respectively; however, individual measurements were +/- 5 ppm for the Orbitrap
      and greater than 10 ppm for the Q-TOF. Relative isotopic abundance measurements
      for A + 1 were within 5% of the theoretical value if the intensity of the
      monoisotopic peak was greater than 1E7 for the Orbitrap and 1E5 for the Q-TOF,
      where an increase in error is observed with a decrease in intensity. Furthermore,
      complicating factors were found in the data that would impact automated data
      analysis strategies, including coeluting species that interfere with
      detectability and relative isotopic abundance measurements. The implications of
      these findings will be discussed with an emphasis on reasonable expectations from
      these instruments, guidelines for experimental workflows, data analysis
      considerations, and software design for non-targeted analyses. 

PMID- 24729192
TI  - A novel poly(amido amine)-dendrimer-based hydrogel as a mimic for the
      extracellular matrix.
AB  - The extracellular matrix is mimicked by a novel dendrimer-based hydrogel, which
      exhibits a highly interconnected porous network, enhanced mechanical stiffness,
      and a low swelling ratio. The hydrogel system supports the proliferation and
      differentiation of mesenchymal stem cells without any cytotoxic effects. This
      dendrimer-based hydrogel may serve as a model for developing new advanced
      materials with applications in tissue engineering. 

PMID- 24729193
TI  - Binge eating in interview versus self-report: different diagnoses show different
      divergences.
AB  - OBJECTIVE: Binge eating (BE) is diagnostically important for eating disorders
      (EDs) but difficult to measure validly and reliably. The study compared interview
      and questionnaire formats regarding the proportion of patients in each diagnostic
      group who reported BE. METHOD: Data came from the clinical Stepwise ED database
      (N=3508 adults and 1354 children/adolescents), representing the full range of ED
      diagnoses. Methods used were the Structured ED Interview and the ED Examination
      Questionnaire. RESULTS: Opposite discrepancies were observed between methods
      depending on ED diagnosis, such that a higher number of restrictive patients
      reported BE on the questionnaire than the interview, whereas the opposite was
      true for bulimic patients. DISCUSSION: The findings have important clinical and
      theoretical implications and suggest that BE assessment is more complex than
      previously believed.

PMID- 24729194
TI  - The prevalence of binge eating disorder in a sample of college students in the
      north of Portugal.
AB  - Binge eating disorder (BED) has important associated comorbidities and has been
      recently considered as a diagnostic category in the Diagnostic and Statistical
      Manual of Mental Disorders - Fifth Edition. This study investigates the
      prevalence of BED in a sample of college students using a two-stage design.
      Between October 2008 and July 2009, 805 students attending a public college
      campus completed the Questionnaire on Eating and Weight Patterns - Revised to
      screen for possible cases. Eighty-five students meeting key criteria for BED were
      invited for a second stage interview using the Eating Disorder Examination. At
      stage 1, 9.6% of the subjects reported binge eating episodes. At stage 2, a
      prevalence rate of 0.5% for BED was found, and 1% if the criterion for large
      amount of food was excluded.

PMID- 24729196
TI  - Chronic myeloid leukemia: 2014 update on diagnosis, monitoring, and management.
AB  - DISEASE OVERVIEW: Chronic Myeloid Leukemia (CML) is a myeloproliferative neoplasm
      with an incidence of 1-2 cases per 100,000 adults, and accounts for ~15% of newly
      diagnosed cases of leukemia in adults. DIAGNOSIS: CML is characterized by a
      balanced genetic translocation, t(9;22)(q34;q11.2), involving a fusion of the
      Abelson oncogene (ABL) from chromosome 9q34 with the breakpoint cluster region
      (BCR) gene on chromosome 22q11.2. This rearrangement is known as the Philadelphia
      chromosome. The molecular consequence of this translocation is the generation of
      a BCR-ABL fusion oncogene, which in turn translates into a Bcr-Abl oncoprotein.
      FRONTLINE THERAPY: Three tyrosine kinase inhibitors (TKIs), imatinib, nilotinib,
      and dasatinib have been approved by the US Food and Drug Administration for the
      first-line treatment of patients with newly diagnosed CML in chronic phase (CML
      CP). Clinical trials with second generation TKIs reported significantly deeper
      and faster responses; their impact on long-term survival remains to be
      determined. SALVAGE THERAPY: For patients who fail frontline therapy, second-line
      options include second and third generation TKIs. Although second and third
      generation TKIs are potent and specific BCR-ABL TKIs, they exhibit unique
      pharmacological profiles and response patterns relative to different patient
      characteristics, such as patients comorbidities, disease stage, and BCR-ABL
      mutational status. Patients who develop the T315I "gatekeeper" mutation display
      resistance to all currently available TKIs except ponatinib. Allogeneic
      transplantation remains an important therapeutic option for CML-CP who have
      failed at least 2 TKIs, and for all patients in advanced phase disease.

PMID- 24729197
TI  - Terminal imido rhodium complexes.
AB  - Compounds of the late transition metals with M=X multiple bonds (X=CR2, NR, O)
      represent a synthetic challenge, partly overcome by preparative chemists, but
      with noticeable gaps in the second- and third-row elements. For example, there
      are no isolated examples of terminal imido rhodium complexes known to date.
      Described herein is the isolation, characterization, and some preliminary
      reactivity studies of the first rhodium complexes [Rh(PhBP3)(NR)]
      (PhBP3=PhB{CH2PPh2}3) with a multiple and terminal Rh=N bond. These imido
      compounds result from reactions of organic azides with the corresponding
      rhodium(I) complex having a labile ligand, and display a pseudo-tetrahedral core
      geometry with an almost linear Rh-N-C arrangement [177.5(2) degrees ] and a short
      Rh-N bond [1.780(2) A]. We also show that the Rh=N bond undergoes protonation at
      the nitrogen atom or addition of H2 , and also engages in nitrene-group transfer
      and cycloaddition reactions.

PMID- 24729198
TI  - Non-invasive brain stimulation techniques for chronic pain.
AB  - BACKGROUND: This is an updated version of the original Cochrane review published
      in 2010, Issue 9. Non-invasive brain stimulation techniques aim to induce an
      electrical stimulation of the brain in an attempt to reduce chronic pain by
      directly altering brain activity. They include repetitive transcranial magnetic
      stimulation (rTMS), cranial electrotherapy stimulation (CES), transcranial direct
      current stimulation (tDCS) and reduced impedance non-invasive cortical
      electrostimulation (RINCE). OBJECTIVES: To evaluate the efficacy of non-invasive
      brain stimulation techniques in chronic pain. SEARCH METHODS: We searched CENTRAL
      (2013, Issue 6), MEDLINE, EMBASE, CINAHL, PsycINFO, LILACS and clinical trials
      registers. The original search for the review was run in November 2009 and
      searched all databases from their inception. To identify studies for inclusion in
      this update we searched from 2009 to July 2013. SELECTION CRITERIA: Randomised
      and quasi-randomised studies of rTMS, CES, tDCS or RINCE if they employed a sham
      stimulation control group, recruited patients over the age of 18 with pain of
      three months duration or more and measured pain as a primary outcome. DATA
      COLLECTION AND ANALYSIS: Two authors independently extracted and verified data.
      Where possible we entered data into meta-analyses. We excluded studies judged as
      being at high risk of bias from the analysis. We used the GRADE system to
      summarise the quality of evidence for core comparisons. MAIN RESULTS: We included
      an additional 23 trials (involving 773 participants randomised) in this update,
      making a total of 56 trials in the review (involving 1710 participants
      randomised). This update included a total of 30 rTMS studies, 11 CES, 14 tDCS and
      one study of RINCE(the original review included 19 rTMS, eight CES and six tDCS
      studies). We judged only three studies as being at low risk of bias across all
      criteria.Meta-analysis of studies of rTMS (involving 528 participants)
      demonstrated significant heterogeneity. Pre-specified subgroup analyses suggest
      that low-frequency stimulation is ineffective (low-quality evidence) and that
      rTMS applied to the dorsolateral prefrontal cortex is ineffective (very low
      quality evidence). We found a short-term effect on pain of active high-frequency
      stimulation of the motor cortex in single-dose studies (low-quality evidence,
      standardised mean difference (SMD) 0.39 (95% confidence interval (CI) -0.27 to 
      0.51 P < 0.01)). This equates to a 12% (95% CI 8% to 15%) reduction in pain,
      which does not exceed the pre-established criteria for a minimal clinically
      important difference (>= 15%). Evidence for multiple-dose studies was
      heterogenous but did not demonstrate a significant effect (very low-quality
      evidence).For CES (six studies, 270 participants) no statistically significant
      difference was found between active stimulation and sham (low-quality
      evidence).Analysis of tDCS studies (11 studies, 193 people) demonstrated
      significant heterogeneity and did not find a significant difference between
      active and sham stimulation (very low-quality evidence). Pre-specified subgroup
      analysis of tDCS applied to the motor cortex (n = 183) did not demonstrate a
      statistically significant effect and this lack of effect was consistent for
      subgroups of single or multiple-dose studies.One small study (n = 91) at unclear
      risk of bias suggested a positive effect of RINCE over sham stimulation on pain
      (very low-quality evidence).Non-invasive brain stimulation appears to be
      frequently associated with minor and transient side effects, though there were
      two reported incidences of seizure related to active rTMS in the included
      studies. AUTHORS' CONCLUSIONS: Single doses of high-frequency rTMS of the motor
      cortex may have small short-term effects on chronic pain. It is likely that
      multiple sources of bias may exaggerate this observed effect. The effects do not
      meet the predetermined threshold of minimal clinical significance and multiple
      dose studies do not consistently demonstrate effectiveness. The available
      evidence suggests that low-frequency rTMS, rTMS applied to the pre-frontal
      cortex, CES and tDCS are not effective in the treatment of chronic pain. While
      the broad conclusions for rTMS and CES have not changed substantially, the
      addition of this new evidence and the application of the GRADE system has
      modified some of our interpretation and the conclusion regarding the
      effectiveness of tDCS has changed. We recommend that previous readers should re
      read this update. There is a need for larger, rigorously designed studies,
      particularly of longer courses of stimulation. It is likely that future evidence
      may substantially impact upon the presented results.

PMID- 24729199
TI  - The role of patient's profile and allogeneic blood transfusion in development of
      post-cardiac surgery infections: a retrospective study.
AB  - OBJECTIVES: We aimed to investigate the association of patient characteristics
      and allogeneic blood transfusion products in development of post-cardiac surgery
      nosocomial infections. METHODS: This retrospective study was conducted in 7888
      patients undergoing cardiac surgery with median sternotomy and cardiopulmonary
      bypass. Multivariable logistic regression analysis was used for independent
      effect of variables on infections. RESULTS: A total of 970 (12.3%) patients
      developed one or several types of postoperative infections. Urinary (n = 351,
      4.4%) and pulmonary tract infections (n = 478, 6.1%) occurred more frequently
      than sternal wound infections (superficial: n = 102, 1.3%, deep: n = 72, 0.9%)
      and donor site infections (n = 61, 0.8%). Interventions, including valve
      replacement (P = 0.002) and coronary artery bypass grafting combined with valve
      replacement (P = 0.012), were associated with increased risk of several types of
      postoperative infections. Patients' profiles changed substantially over the
      years; morbid obesity (P = 0.019), smoking (P = 0.001) and diabetes mellitus (P =
      0.001) occur more frequently nowadays. Furthermore, surgical site infections
      showed to be related to morbid obesity (P < 0.001) and higher risk stratification
      (P = 0.031). Smoking (P < 0.001) and chronic obstructive pulmonary disease (P <
      0.001) were related to pulmonary tract infections. In addition, diabetic patients
      developed more sepsis (P = 0.003) and advanced age was associated with
      development of urinary tract infections (P < 0.001). Even after correcting for
      other factors, blood transfusion was associated with all types of postoperative
      infection (P < 0.001). This effect remained present in both leucocyte-depleted
      and non-leucocyte-depleted transfusion. CONCLUSIONS: Our data showed that post
      cardiac surgery infections occur more frequently in patients with predetermined
      risk factors. The amount of blood transfusions was integrally related to every
      type of postoperative infection.

PMID- 24729200
TI  - Strangulation of aberrant artery in extralobar pulmonary sequestration on video
      imaging.
AB  - We report a case of an 18-year old female patient with symptomatic extralobar
      pulmonary sequestration. The initial symptom was sudden-onset right lateral
      abdominal pain. Enhanced computed tomography showed a 5 cm in diameter, spindle
      shaped mass located in the costophrenic sinus with no aberrant artery.
      Exploratory thoracoscopy showed a haemorrhagic mass caused by strangulation of an
      aberrant vessel originating from the intercostal artery. Pathological findings
      revealed pulmonary sequestration with haemorrhagic infarction. The strangulated
      aberrant artery was clearly demonstrated by video imaging. 

PMID- 24729201
TI  - Does endovascular treatment of infra-inguinal arterial disease with drug-eluting
      stents offer better results than angioplasty with or without bare metal stents?
AB  - A best evidence topic in vascular and endovascular surgery was developed
      according to a structured protocol. The question addressed was whether treatment
      of infra-inguinal arterial occlusive disease with drug-eluting stents (DESs)
      provides improved outcomes compared with bare metal stents (BMSs) or percutaneous
      balloon angioplasty (PTA) alone. Altogether, 136 papers were found using the
      reported searches, of which 5 provided the best evidence to answer the question.
      All papers represent either level 1 or 2 evidence. The authors, journal, date,
      country of publication, patient group studied, study type, relevant outcomes and
      results of these papers are tabulated. Main outcome measures varied among the
      studies, and included patency, in-stent restenosis, target lesion
      revascularization, major adverse events, clinical improvement and limb salvage.
      Evidence on the comparative efficacy of DESs in femoro-popliteal arterial disease
      is mainly based on two randomized, controlled trials. Paclitaxel-eluting stents
      were evaluated in the Zilver PTX trial and demonstrated superior 2-year results
      to either BMSs or PTA, as indicated/shown by patency (DES vs PTA, 74.8 vs 26.5%,
      P < 0.01), clinical benefit (DES vs PTA, P < 0.01) and event-free survival (DES
      vs PTA, 86.6 vs 77.9%, P = 0.02). However, the SIROCCO trial found that the
      sirolimus-eluting stent did not exhibit statistically significant differences in
      2-year in-stent restenosis (22.9 vs 21.1%) and target lesion revascularization (6
      vs 13%) compared with the BMS. Treatment of infra-politeal arterial disease with
      DESs was related with superior outcomes to those of BMSs, as indicated/shown by
      patency, freedom from target lesion revascularization and freedom from major
      adverse events. Furthermore, the ACHILLES trial, the only published trial
      comparing the infra-popliteal DES with PTA, revealed lower angiographic
      restenosis (22.4 vs 41.9%, P = 0.019) and greater vessel patency (75 vs 57.1%, P
      = 0.025) in the DES group at 1 year. However, data related to clinical parameters
      in patients with critical limb ischaemia secondary to infrageniculate arterial
      disease, such as limb salvage and ulcer healing, are insufficient. In conclusion,
      treatment of infra-inguinal arterial disease with DES is safe and seems to be
      superior to treatment with PTA alone or BMS. The role of DES in sustained
      improvement in clinical outcome end-points, such as limb salvage, remains to be
      elucidated. 

PMID- 24729202
TI  - Intrapericardial bronchogenic duplication cyst.
AB  - Bronchogenic cysts arise from an abnormal budding of the ventral diverticulum of
      the foregut or the tracheobronchial tree, during embryogenesis. Intrapericardial
      cysts are rare, accounting for 27% of bronchogenic cysts. In this case report, we
      present a young woman with a symptomatic intrapericardial bronchogenic cyst
      compressing the superior vena cava. The cyst was resected via median sternotomy,
      alleviating the patients' preoperative symptoms. 

PMID- 24729203
TI  - Capillary electrophoresis for the analysis of the effect of sample preparation on
      early stages of Abeta1-40 aggregation.
AB  - Aggregation of the amyloid-beta protein (Abeta) contributes to the
      neurodegeneration characteristic of Alzheimer's disease. Of particular importance
      are the early stages of aggregation, which involve the formation of soluble
      oligomers and protofibrils. In these studies, we demonstrate the potential for CE
      with UV detection using a polyethylene oxide separation matrix to identify the
      evolution of various oligomeric species of Abeta1-40 . To demonstrate the
      efficacy of this technique, UV-CE was utilized to compare two methods commonly
      used to prepare Abeta for aggregation experiments and their effect on the
      formation of early aggregates. SEC-purified Abeta1-40 initially contained more
      small species, including monomer, than did freshly dissolved Abeta1-40 pretreated
      with hexafluoroisopropanol. Strikingly, the lag time to oligomer formation for
      SEC-isolated Abeta1-40 samples was ~23 h shorter compared to freshly dissolved
      Abeta1-40 samples. Furthermore, oligomers formed from the aggregation of SEC
      purified Abeta1-40 persisted within solution for a longer period of time. These
      results indicate that the initial sample preparation has a drastic influence on
      the early stages of Abeta1-40 aggregation. This is the first report of the use of
      UV-CE with a separation matrix to study the effect of sample preparation on early
      aggregation of Abeta1-40 . UV-CE was also used in parallel with dot blot analysis
      and inhibitory compounds to discern structural characteristics of individual
      oligomer peaks, demonstrating the capacity of UV-CE as a complimentary technique
      to further understand the aggregation process.

PMID- 24729204
TI  - Copper-catalyzed C-2 arylation or vinylation of indole derivatives with iodonium
      salts.
AB  - Copper-catalyzed C-2 arylation and vinylation of indole derivatives with iodonium
      salts have been realized. This method, featuring a simple operational procedure,
      mild reaction conditions, and a wide substrate scope, provided versatile indole
      derivatives with direct and selective functionalization at the C-2 position of
      the indole core. In the presence of excess amounts of iodonium salts, cascade C-2
      arylation and dearomatization through the C-3 arylation reaction also proceeded
      smoothly. 

PMID- 24729208
TI  - Mitochondrial genetic abnormalities after radiation exposure.
AB  - Because mitochondria are prone to oxidative stress, damage to their DNA might
      provide a record of radiation exposure. We measured the effect of gamma radiation
      on mitochondrial DNA (mtDNA) copy number and common deletion (mito-CD) mutations
      using Beas-2B and HFL-1 cells lines and C3H/HeJ mice exposed to total-body
      irradiation (TBI) and sub-TBI. DNA was extracted 5 days after cell irradiation or
      12 months after animal exposure. We found that: (1) natural ratios of mtDNA/nDNA
      and mito-CD/mtDNA varied between cell lines; (2) mtDNA copy number decreased in
      Beas-2B and increased in HFL-1 following 2 Gy; (3) mito-CD in both cell lines
      increased after 2 Gy; (4) in aged mice, the natural ratios of mtDNA/nDNA varied
      from 0.723 to 8.146 in different tissues; (5) in kidney tissue, TBI and sub-TBI
      mildly increased mtDNA copy number but substantially increased mtDNA-CD; and (6)
      in liver tissue, TBI and sub-TBI induced a slight increase in mtDNA copy number
      and a larger increase in mtDNA-CD. These findings indicate that mtDNA copy number
      varies in time by cell type, but there is a substantial and sustained increase in
      mtDNA mutations that occurs to different degrees in different tissues and cells
      following irradiation. 

PMID- 24729207
TI  - Intimate partner violence: associations with low infant birthweight in a South
      African birth cohort.
AB  - Violence against women is a global public health problem. Exposure to intimate
      partner violence (IPV) during pregnancy has been associated with a number of
      adverse maternal and fetal outcomes, including delivery of a low birthweight
      (LBW) infant. However, there is a paucity of data from low-middle income
      countries (LMIC). We examined the association between antenatal IPV and
      subsequent LBW in a South African birth cohort. This study reports data from the
      Drakenstein Child Lung Health Study (DCLHS), a multidisciplinary birth cohort
      investigation of the influence of a number of antecedent risk factors on maternal
      and infant health outcomes over time. Pregnant women seeking antenatal care were
      recruited at two different primary care clinics in a low income, semi-rural area
      outside Cape Town, South Africa. Antenatal trauma exposure was assessed using the
      Childhood Trauma Questionnaire (CTQ) and an IPV assessment tool specifically
      designed for the purposes of this study. Potential confounding variables
      including maternal sociodemographics, pregnancy intention, partner support,
      biomedical and mental illness, substance use and psychosocial risk were also
      assessed. Bivariate and multiple regression analyses were performed to determine
      the association between IPV during pregnancy and delivery of an infant with LBW
      and/or low weight-for-age z (WAZ) scores. The final study sample comprised 263
      mother-infant dyads. In multiple regression analyses, the model run was
      significant [r2  = 0.14 (adjusted r2  = 0.11, F(8, 212) = 4.16, p = 0.0001].
      Exposure to physical IPV occurring during the past year was found to be
      significantly associated with LBW [t = -2.04, p = 0.0429] when controlling for
      study site (clinic), maternal height, ethnicity, socioeconomic status, substance
      use and childhood trauma. A significant association with decreased WAZ scores was
      not demonstrated. Exposure of pregnant women to IPV may impact newborn health.
      Further research is needed in this field to assess the relevant underlying
      mechanisms, to inform public health policies and to develop appropriate trauma
      IPV interventions for LMIC settings.

PMID- 24729209
TI  - Crediting six discoverers of oxygen.
AB  - Recent events have called long-overdue attention to one of the first
      investigators to discover the roles of something in air changing the color of the
      pulmonary blood flowing through the lung. 

PMID- 24729210
TI  - Hypoxia in tumors: pathogenesis-related classification, characterization of
      hypoxia subtypes, and associated biological and clinical implications.
AB  - Hypoxia is a hallmark of tumors leading to (mal-)adaptive processes, development
      of aggressive phenotypes and treatment resistance. Based on underlying mechanisms
      and their duration, two main types of hypoxia have been identified, coexisting
      with complex spatial and temporal heterogeneities. Chronic hypoxia is mainly
      caused by diffusion limitations due to enlarged diffusion distances and adverse
      diffusion geometries (e.g., concurrent vs. countercurrent microvessels, Krogh-
      vs. Hill-type diffusion geometry) and, to a lesser extent, by hypoxemia (e.g., in
      anemic patients, HbCO formation in heavy smokers), and a compromised perfusion or
      flow stop (e.g., due to disturbed Starling forces or intratumor solid stress).
      Acute hypoxia mainly results from transient disruptions in perfusion (e.g.,
      vascular occlusion by cell aggregates), fluctuating red blood cell fluxes or
      short-term contractions of the interstitial matrix. In each of these hypoxia
      subtypes oxygen supply is critically reduced, but perfusion-dependent nutrient
      supply, waste removal, delivery of anticancer or diagnostic agents, and repair
      competence can be impaired or may not be affected. This detailed differentiation
      of tumor hypoxia may impact on our understanding of tumor biology and may aid in
      the development of novel treatment strategies, tumor detection by imaging and
      tumor targeting, and is thus of great clinical relevance. 

PMID- 24729211
TI  - Heterogeneity in tissue oxygenation: from physiological variability in normal
      tissues to pathophysiological chaos in malignant tumours.
AB  - Heterogeneity is a feature of both normal oxygen supply to tissue and of a supply
      that is disturbed due to a wide range of different pathologies. Here, the
      physiological importance of heterogeneity of tissue oxygenation is revisited. The
      anatomical and functional basis for heterogeneity of blood flow, local and
      regional regulatory mechanisms in normal tissues and the pathophysiology of the
      failure of regulation will be examined.Under physiological conditions, regulation
      of blood flow distributions at global, regional and microregional levels play
      coordinated roles in ensuring adequate O2 supply to all tissue cells. How this is
      achieved may be organ-/organ layer-specific, depending on its function and
      priorities to match local O2 delivery to consumption. Examples where these
      regulatory mechanisms break down under conditions of ischaemia and shock will
      also be given.In contrast, pathologic heterogeneity in tissue oxygenation
      resulting from uncontrolled, chaotic growth as seen in malignant tumours
      represents a pathophysiological status that is not predictable which, in general,
      is associated with chronic and acute hypoxia. This can have fatal consequences
      due to hypoxia- induced (mal-)adaptive processes, malignant tumour progression
      and treatment resistance. 

PMID- 24729212
TI  - Oxygen diffusion: an enzyme-controlled variable parameter.
AB  - Previous oxygen microelectrode studies have shown that the oxygen diffusion
      coefficient (DO2) increases during extracellular PO2 decreases, while
      intracellular PO2 remained unchanged and thus cell function (spike activity of
      neurons). Oxygen dependency of complex multicellular organisms requires a stable
      and adequate oxygen supply to the cells, while toxic concentrations have to be
      avoided. Oxygen brought to the tissue by convection diffuses through the
      intercellular and cell membranes, which are potential barriers to diffusion. In
      gerbil brain cortex, PO2 and DO2 were measured by membrane-covered and by bare
      gold microelectrodes, as were also spike potentials. Moderate respiratory hypoxia
      was followed by a primary sharp drop of tissue PO2 that recovered to higher
      values concomitant with an increase of DO2. A drop in intracellular PO2 recovered
      immediately. Studies on the abdominal ganglion of aplysia californica showed
      similar results.Heterogeneity is a feature of both normal oxygen supply to tissue
      and supply due to a wide range of disturbances in oxygen supply. Oxygen diffusion
      through membranes is variable thereby ensuring adequate intracellular PO2. Cell
      derived glucosamine oxidase seems to regulate the polymerization/depolymerisation
      ratio of membrane mucopolysaccharides and thus oxygen diffusion.Variability of
      oxygen diffusion is a decisive parameter for regulating the supply/demand ratio
      of oxygen supply to the cell; this occurs in highly developed animals as well as
      in species of a less sophisticated nature. Autoregulation of oxygen diffusion is
      as important as the distribution/perfusion ratio of the capillary meshwork and as
      the oxygen extraction ratio in relation to oxygen consumption of the cell. Oxygen
      diffusion resistance is the cellular protection against luxury oxygen supply
      (which can result in toxic oxidative species leading to mutagenesis).

PMID- 24729213
TI  - Role of microvascular shunts in the loss of cerebral blood flow autoregulation.
AB  - Historically, determination of the critical cerebral perfusion pressure (CPP) was
      done in animals by a progressive lowering of arterial pressure yielding a nominal
      critical CPP of 60 mmHg. Subsequently, it was shown that if the CPP was decreased
      by increasing intracranial pressure (ICP), critical CPP fell to 30 mmHg. This
      discrepancy was unexplained. We recently provided evidence that the decrease in
      critical CPP was due to microvascular shunting resulting in maintained cerebral
      blood flow (CBF) at a lower CPP. We demonstrated by a progressive increase in ICP
      in rats using two-photon laser scanning microscopy (2PLSM) that the transition
      from capillary to microvascular shunt flow is a pathological process. We surmise
      that the loss of CBF autoregulation revealed by decreasing arterial pressure
      occurs by dilation of normal cerebral blood vessels whereas that which occurs by
      increasing ICP is due to microvascular shunting. Our observations indicate that
      the loss of CBF autoregulation we observed in brain injured patients that changes
      on an hourly or daily basis reflects an important pathophysiological process
      impacting on outcome that remains to be determined. 

PMID- 24729214
TI  - Impact of hypoxia-related tumor acidosis on cytotoxicity of different
      chemotherapeutic drugs in vitro and in vivo.
AB  - Extracellular acidosis in tumors leads to an activation of the p-glycoprotein
      (Pgp) drug transporter. In the present study the cytotoxicity of different
      chemotherapeutic drugs and its dependence on the Pgp activity during acidosis
      were analyzed in vitro and in vivo. Treating R3327-AT1, Pgp-positive tumor cells
      at pH 7.4 with daunorubicin, cisplatin or docetaxel led to marked apoptosis
      induction and cell death. Under acidic (pH 6.6) conditions cytotoxicity of
      daunorubicin or docetaxel was significantly reduced whereas cisplatin-induced
      cell death was almost pH-independent. Inhibiting Pgp with verapamil reversed the
      acidosis-induced chemoresistance against daunorubicin and docetaxel. The Pgp
      expression was unaffected by pH. In vivo the cytotoxicity of daunorubicin and
      docetaxel was also pH dependent. When acidifying the tumors by forcing glycolytic
      metabolism, apoptosis induction decreased significantly indicating a reduced
      chemosensitivity. The cytotoxic effect of cisplatin in vivo was unaffected by the
      tumor pH. Since daunorubicin and docetaxel (but not cisplatin) are substrates of
      the Pgp, these results underline the influence of the tumor acidosis on the Pgp
      mediated chemoresistance which can be counteracted by inhibition of the drug
      transporter. 

PMID- 24729215
TI  - The founding of ISOTT: the Shamattawa of engineering science and medical science.
AB  - The founding of ISOTT was based upon the blending of Medical and Engineering
      sciences. This occurrence is portrayed by the Shamattawa, the joining of the
      Chippewa and Flambeau rivers. Beginning with Carl Scheele's discovery of oxygen,
      the medical sciences advanced the knowledge of its importance to physiological
      phenomena. Meanwhile, engineering science was evolving as a mathematical
      discipline used to define systems quantitatively from basic principles. In
      particular, Adolf Fick's employment of a gradient led to the formalization of
      transport phenomena. These two rivers of knowledge were blended to found ISOTT at
      Clemson/Charleston, South Carolina, USA, in 1973.The establishment of our society
      with a mission to support the collaborative work of medical scientists,
      clinicians and all disciplines of engineering was a supporting step in the
      evolution of bioengineering. Traditional engineers typically worked in areas not
      requiring knowledge of biology or the life sciences. By encouraging collaboration
      between medical science and traditional engineering, our society became one of
      the forerunners in establishing bioengineering as the fifth traditional
      discipline of engineering. 

PMID- 24729216
TI  - A tale of two methods: combining near-infrared spectroscopy with MRI for studies
      of brain oxygenation and metabolism.
AB  - Combining magnetic resonance imaging (MRI) with near-infrared spectroscopy (NIRS)
      leads to excellent synergies which can improve the interpretation of either
      method and can provide novel data with respect to measuring brain oxygenation and
      metabolism. MRI has good spatial resolution, can detect a range of physiological
      parameters and is sensitive to changes in deoxyhemoglobin content. NIRS has lower
      spatial resolution, but can detect, and with specific technologies, quantify,
      deoxyhemoglobin, oxyhemoglobin, total hemoglobin and cytochrome oxidase. This
      paper reviews the application of both methods, as a multimodal technology, for
      assessing changes in brain oxygenation that may occur with changes in functional
      activation state or metabolic rate. Examples of hypoxia and ischemia are shown.
      Data support the concept of reduced metabolic rate resulting from
      hypoxia/ischemia and that metabolic rate in brain is not close to oxygen
      limitation during normoxia. We show that multimodal MRI and NIRS can provide
      novel information for studies of brain metabolism. 

PMID- 24729217
TI  - Advances in probes and methods for clinical EPR oximetry.
AB  - EPR oximetry, which enables reliable, accurate, and repeated measurements of the
      partial pressure of oxygen in tissues, provides a unique opportunity to
      investigate the role of oxygen in the pathogenesis and treatment of several
      diseases including cancer, stroke, and heart failure. Building on significant
      advances in the in vivo application of EPR oximetry for small animal models of
      disease, we are developing suitable probes and instrumentation required for use
      in human subjects. Our laboratory has established the feasibility of clinical EPR
      oximetry in cancer patients using India ink, the only material presently approved
      for clinical use. We now are developing the next generation of probes, which are
      both superior in terms of oxygen sensitivity and biocompatibility including an
      excellent safety profile for use in humans. Further advances include the
      development of implantable oxygen sensors linked to an external coupling loop for
      measurements of deep-tissue oxygenations at any depth, overcoming the current
      limitation of 10 mm. This paper presents an overview of recent developments in
      our ability to make meaningful measurements of oxygen partial pressures in human
      subjects under clinical settings. 

PMID- 24729218
TI  - Real-time, in vivo determination of dynamic changes in lung and heart tissue
      oxygenation using EPR oximetry.
AB  - The use of electron paramagnetic resonance (EPR) oximetry for oxygen measurements
      in deep tissues (>1 cm) is challenging due to the limited penetration depth of
      the microwave energy. To overcome this limitation, implantable resonators, having
      a small (0.5 mm diameter) sensory loop containing the oxygen-sensing paramagnetic
      material connected by a pair of twisted copper wire to a coupling loop (8-10 mm
      diameter), have been developed, which enable repeated measurements of deep-tissue
      oxygen levels (pO2, partial pressure of oxygen) in the brain and tumors of
      rodents. In this study, we have demonstrated the feasibility of measuring dynamic
      changes in pO2 in the heart and lung of rats using deep-tissue implantable oxygen
      sensors. The sensory loop of the resonator contained lithium octa-n
      butoxynaphthalocyanine (LiNc-BuO) crystals embedded in polydimethylsiloxane
      (PDMS) polymer and was implanted in the myocardial tissue or lung pleura. The
      external coupling loop was secured subcutaneously above chest. The rats were
      exposed to different breathing gas mixtures while undergoing EPR measurements.
      The results demonstrated that implantable oxygen sensors provide reliable
      measurements of pO2 in deep tissues such as heart and lung under adverse
      conditions of cardiac and respiratory motions. 

PMID- 24729219
TI  - Modulation of hypoxia by magnetic nanoparticle hyperthermia to augment
      therapeutic index.
AB  - A hypoxic microenvironment in solid tumors has been known to cause resistance to
      standard therapies and to increase the malignant potential of tumors. The
      utilization of magnetic nanoparticle hyperthermia (mNPH) has shown promise in
      improving therapeutic outcome by (1) killing of hypoxic tumor cells directly and
      (2) increasing tumor oxygenation and therefore susceptibility to therapies. In
      this study, the interaction of a hypoxic microenvironment with mNPH efficacy was
      investigated in a human breast cancer orthotopic xenograft model. Using electron
      paramagnetic resonance (EPR) to assess in vivo oxygen concentration in tumors
      repeatedly and non-invasively, we found that mNPH increased tumor pO2 from 3.5 to
      68.8 mmHg on average for up to 10 days. Tumors treated once with mNPH showed
      growth delay. On Transmission Electron Microscopy, magnetic nanoparticles (mNPs)
      were localized intracellularly in multiple vesicles in the cytoplasm of cells
      within tumors 48 h after incubation of mNP. In conclusion, mNPH increased tumor
      oxygenation in vivo and resulted in decreased growth of hypoxic tumors. Future
      studies will establish tumor pO2-guided multimodal therapies, such as mNPH and
      radiation, to improve therapeutic efficacy.

PMID- 24729220
TI  - Skeletal muscle and glioma oxygenation by carbogen inhalation in rats: a
      longitudinal study by EPR oximetry using single-probe implantable oxygen sensors.
AB  - The feasibility of EPR oximetry using a single-probe implantable oxygen sensor
      (ImOS) was tested for repeated measurement of pO2 in skeletal muscle and ectopic
      9L tumors in rats. The ImOS (50 mm length) were constructed using nickel-chromium
      alloy wires, with lithium phthalocyanine (LiPc, oximetry probe) crystals loaded
      in the sensor loop and coated with AF 2400((r)) Teflon. These ImOS were implanted
      into the skeletal muscle in the thigh and subcutaneous 9L tumors. Dynamic changes
      in tissue pO2 were assessed by EPR oximetry at baseline, during tumor growth, and
      repeated hyperoxygenation with carbogen breathing. The mean skeletal muscle pO2
      of normal rats was stable and significantly increased during carbogen inhalation
      in experiments repeated for 12 weeks. The 9L tumors were hypoxic with a tissue
      pO2 of 12.8 +/- 6.4 mmHg on day 1; however, the response to carbogen inhalation
      varied among the animals. A significant increase in the glioma pO2 was observed
      during carbogen inhalation on day 9 and day 14 only. In summary, EPR oximetry
      with ImOS allowed direct and longitudinal oxygen measurements in deep muscle
      tissue and tumors. The heterogeneity of 9L tumors in response to carbogen
      highlights the need to repeatedly monitor pO2 to confirm tumor oxygenation so
      that such changes can be taken into account in planning therapies and
      interpreting results.

PMID- 24729221
TI  - Recurrent low-dose chemotherapy to inhibit and oxygenate head and neck tumors.
AB  - A lack of strategy to counteract hypoxia (pO2 < 10-15 mmHg) and technique to
      repeatedly measure tumor pO2 has restricted therapeutic optimization. We report
      the results obtained with an innovative anti-angiogenic strategy of recurrent low
      dose (metronomic) chemotherapy to modulate hypoxia and growth of the Head and
      Neck tumor xenografts.The FaDu tumors were established in the flank of immune
      deficient mice and EPR oximetry with lithium phthalocyanine crystals was used to
      follow the temporal changes in tumor pO2 on treatment with gemcitabine including
      controls for three weeks. The FaDu tumors were hypoxic with a baseline (pre
      treatment) pO2 of 2-8 mmHg. A transient increase in the tumor pO2 was evident on
      day 3 on treatment with a conventional schedule of gemcitabine (150 mg/kg, d1,
      d8, d15). No significant change in the tumor pO2 on treatment with metronomic
      gemcitabine (25 mg/kg on d1, d3, d5 for 3 weeks) was observed. However, tumor pO2
      increased significantly on d15-d18 during treatment with a metronomic schedule of
      15 mg/kg gemcitabine (d1, d3, d5 for 3 weeks). A modest decrease in the tumor
      growth was evident on treatment with conventional gemcitabine. Notably, tumor
      growth was significantly inhibited by metronomic (25 and 15 mg/kg) gemcitabine
      treatment. The immunohistochemistry (IHC) analyses of the tumor samples indicate
      a decrease in HIF-1alpha and TSP-1 on treatment with metronomic gemcitabine.In
      conclusion, a significant inhibition of tumor growth on treatment with metronomic
      gemcitabine was observed; however, the increase in pO2 was dose dependent. EPR
      oximetry can be used to follow the temporal changes in tumor pO2 to identify a
      therapeutic window on treatment with metronomic chemotherapy for potential
      combination with radiotherapy.

PMID- 24729222
TI  - How in vivo EPR measures and images oxygen.
AB  - The partial pressure of oxygen (pO2) in tissues plays an important role in the
      pathophysiology of many diseases and influences outcome of cancer therapy,
      ischemic heart and cerebrovascular disease treatments and wound healing. Over the
      years a suite of EPR techniques for reliable oxygen measurements has been
      developed. This is a mini-review of pulse EPR in vivo oxygen imaging methods that
      utilize soluble spin probes. Recent developments in pulse EPR imaging technology
      have brought an order of magnitude increase in image acquisition speed,
      enhancement of sensitivity and considerable improvement in the precision and
      accuracy of oxygen measurements.

PMID- 24729223
TI  - What we learn from in vivo EPR oxygen images.
AB  - Distributions of oxygen concentration (pO2) are a critical determinant of normal
      tissue health as well as tumor aggressiveness and response to therapy. A number
      of studies show the value of normal tissue and tumor tissue oxygenation images
      and some of these will be discussed here. A strong correlation between tumor
      hypoxic fraction as measured with electron paramagnetic resonance oxygen imaging
      and radiation treatment success or failure has been found in two separate cancer
      types. Oxygen images of the torso of wild type mice show initial reduction of
      lung, liver, visceral, and muscle pO2 with cyclic halving of fraction of inspired
      oxygen (FiO2), but variation is blunted over an hour. Spontaneous breast cancers
      in Mouse Mammary Tumor Viral (MMTV) promoted-polyoma middle T antigen (PyMT) mice
      with BNIP3, a major factor in promotion of mitochondrial autophagy, knocked out
      will be compared with wild type animals. Preliminary studies for the BNIP3 knock
      out animals show extremely low pO2. The wide variety of studies, in which oxygen
      images can play an integral role, serve to demonstrate the importance of oxygen
      images.

PMID- 24729224
TI  - EPR image based oxygen movies for transient hypoxia.
AB  - Chronic hypoxia strongly affects the malignant state and resistance to therapy
      for tumors. Transient hypoxia has been hypothesized, but not proven to be more
      deleterious. Electron paramagnetic resonance imaging (EPRI) provides non
      invasive, quantitative imaging of static pO2 in vivo. Dynamic EPRI produces pO2
      movies, enabling non-invasive assessment of in vivo pO2 changes, such as
      transient hypoxia. Recent developments have been made to enable Dynamic EPRI.
      Maximally spaced projection sequencing has been implemented to allow for more
      accurate and versatile acquisition of EPRI data when studying dynamic systems.
      Principal component analysis filtering has been employed to enhance SNR. Dynamic
      EPRI studies will provide temporally resolved oxygen movies necessary to perform
      in vivo studies of physiologically relevant pO2 changes in tumors. These oxygen
      movies will allow for the localization/quantification of transient hypoxia and
      will therefore help to disentangle the relationship between chronic and transient
      hypoxia, in order to better understand their roles in therapeutic optimization
      and outcome.

PMID- 24729225
TI  - Repetitive measurements of intrarenal oxygenation in vivo using L band electron
      paramagnetic resonance.
AB  - Intrarenal oxygenation is heterogeneous with oxygen levels normally being highest
      in the superficial cortex and lowest in the inner medulla. Reduced intrarenal
      oxygenation has been implied in the pathology of several kidney diseases.
      However, there is currently no method available to repetitively monitor regional
      renal oxygenation using minimally invasive procedures. We therefore evaluated
      implantable lithium phthalocyanine (LiPc) probes, which display a close
      correlation between EPR line width and oxygen availability.LiPc probes were
      implanted in the kidney cortex and medulla in the same mouse and EPR spectra were
      acquired using a L band scanner during inhalation of air (21 % oxygen) or a
      mixture of air and nitrogen (10 % oxygen). In order to separate the signals from
      the two probes, a 1 G/cm gradient was applied and the signals were derived from
      40 consecutive sweeps. Peak-to-peak comparison of the EPR line was used to
      convert the signal to an approximate oxygen tension in MATLAB. Kidney cortex as
      well as medullary oxygenation was stable over the 45 day period (cortex 56 +/- 7
      mmHg and medulla 43 +/- 6 mmHg). However, 10 % oxygen inhalation significantly
      reduced oxygenation in both cortex (56 +/- 6 to 34 +/- 2 mmHg n = 15 p < 0.05)
      and medulla (42 +/- 5 to 29 +/- 3 mmHg n = 7 p < 0.05).In conclusion, L band EPR
      using LiPc probes implanted in discrete intrarenal structures can be used to
      repetitively monitor regional renal oxygenation. This minimally invasive method
      is especially well suited for conditions of reduced intrarenal oxygenation since
      this increases the signal intensity which facilitates the quantification of the
      EPR signal to absolute oxygenation values. 

PMID- 24729226
TI  - Quantitative hypoxia imaging for treatment planning of radiotherapy.
AB  - Tumour oxygenation is an important determinant of radiotherapy outcome as it
      could modulate cellular radiation sensitivity. Advanced PET imaging able to
      characterise this microenvironmental aspect in vivo might be used to devise
      counteracting therapies as it could provide information on the severity and the
      spatial distribution of the hypoxic regions. This study reviews the advantages
      and limitations of PET for imaging and quantifying tumour hypoxia and proposes a
      novel approach to obtain absolute levels of hypoxia from PET images through the
      use of EPR oximetry. This would offer a significant advantage over proposals
      based on empirical conversions of the intensities in the PET images to relative
      radiosensitivities. Thus, tumour hypoxia must be taken into account at the stage
      of treatment planning for photons and particle therapy by accounting for its
      extent and severity through the use of PET imaging combined with absolute EPR
      measurements. 

PMID- 24729227
TI  - A new flavonoid regulates angiogenesis and reactive oxygen species production.
AB  - The tumor vascular system, which is critical to the survival and growth of solid
      tumors, has been an attractive target for anticancer research. Building on
      studies that show that some flavonoids have anticancer vascular effects, we
      developed and analyzed the flavonoid derivative R24 [3, 6-bis (2-oxiranylmethoxy)
      9H-xanthen-9-one]. A CAM assay revealed that R24 disrupted neovascular formation;
      fewer dendrites were detected and overall dendritic length was shorter in the R24
      treated chicken embryos. The antiproliferative effect of R24 was measured by MTT
      assay in A549 (lung cancer), AsPC-1 (pancreatic cancer), HCT-116 (colorectal
      cancer), and PC-3 (prostate cancer) cell lines. R24 reduced proliferation with an
      IC50 of 3.44, 3.59, 1.22, and 11.83 MUM, respectively. Cell-cycle analysis and
      Annexin-V/propidium iodide staining showed that R24 induced apoptosis. In
      addition, R24 regulated intracellular ROS production in a dose-dependent manner.
      CM-H2DCFDA staining indicated that intracellular ROS production increased with
      the R24 dose. In summary, we found that R24 exhibits potent antiangiogenic and
      antiproliferative effects, induces apoptosis, and promotes ROS production. 

PMID- 24729228
TI  - Angiotensin II reduces transport-dependent oxygen consumption but increases
      transport-independent oxygen consumption in immortalized mouse proximal tubular
      cells.
AB  - Oxidative stress is closely associated with renal dysfunction following diabetes
      and hypertension. Angiotensin II (Ang II) can activate the NADPH-oxidase,
      increasing oxidative stress that is thought to blunt proximal tubular electrolyte
      transport and thereby oxygen consumption (QO2). We investigated the effect of Ang
      II on QO2 in immortalized mouse proximal tubular cells over-expressing the NADPH
      oxidase subunit p22(phox); a model of increased oxidative stress. Cultured cells
      were exposed to either Ang II or H2O2 for 48 h. QO2 was determined during
      baseline (113 mmol/l NaCl; transport-dependent QO2) and during sodium-free
      conditions (transport-independent QO2). Ang II reduced transport-dependent QO2 in
      wild-types, but not in p22(phox) which also displayed increased QO2 at baseline.
      Transport-independent QO2 was increased in p22(phox) and Ang II had no additional
      effect, whereas it increased QO2 in wild-type. Addition of H2O2 reduced transport
      dependent QO2 in wild-types, but not in p22(phox). Transport-independent QO2 was
      unaffected by H2O2. The similar effects of Ang II and H2O2 to reduce transport
      dependent QO2 suggest a direct regulatory role of oxidative stress. In
      accordance, the transport-dependent QO2 was reduced in p22(phox) already during
      baseline. The effects of Ang II on transport-independent QO2 was not replicated
      by H2O2, indicating direct regulation via Ang II-receptors independently of
      oxidative stress. However, the Ang II effect was absent in p22(phox), suggesting
      that oxidative stress also modulates normal Ang II signaling. In conclusion, Ang
      II affects both transport-dependent and transport-independent QO2 in proximal
      tubular cells and may be an important pathway modulating renal QO2.

PMID- 24729229
TI  - Investigation of cerebral autoregulation in the newborn piglet during anaesthesia
      and surgery.
AB  - The relationship between cerebral autoregulation (CA) and the neurotoxic effects
      of anaesthesia with and without surgery is investigated. Newborn piglets were
      randomly assigned to receive either 6 h of anaesthesia (isoflurane) or the same
      with an additional hour of minor surgery. The effect of the spontaneous changes
      in mean arterial blood pressure (MABP) on the cerebral haemodynamics (oxy- and
      deoxy-haemoglobin, HbO2 and Hb) was measured using transverse broadband near
      infrared spectroscopy (NIRS). A marker for impaired CA, concordance between MABP
      and intravascular oxygenation (HbD = HbO2 - Hb) in the ultra-low frequency domain
      (0.0018-0.0083 Hz), was assessed using coherence analysis. Presence of CA
      impairment was not significant but found to increase with surgical exacerbation.
      The impairment did not correlate with histological outcome (presence of cell
      death, apoptosis and microglial activation in the brain). 

PMID- 24729230
TI  - Influence of the maternal use of labetalol on the neurogenic mechanism for
      cerebral autoregulation assessed by means of NIRS.
AB  - Labetalol is a drug used in the treatment of hypertensive disorders of pregnancy
      (HDP). In a previous study we investigated the influence of the maternal use of
      labetalol on the cerebral autoregulation (CA) mechanism of neonates. In that
      study, we found that labetalol induces impaired CA during the first day of life,
      with CA returning to a normal status by the third day after birth. This effect
      was hypothesized to be caused by labetalol-induced vasodilation. However, no
      strong evidence for this claim was found. In this study we aim to find stronger
      evidence for the vasodilation effect caused by labetalol, by investigating its
      effect on the neurogenic mechanism (NM) involved in CA. The status of the NM was
      assessed by means of transfer function analysis between the low frequency content
      of the autonomic control activity (LFA), obtained by processing of the heart rate
      (HR), and the regional cerebral oxygen saturation (rScO2). We found that neonates
      from mothers treated with labetalol presented a lower LFA and an impaired NM
      response during the first day of life, with values returning to normal by the end
      of the third day. These results reflect a vasodilation effect caused by
      labetalol, and indicate that the impaired CA observed in the previous study is
      caused by vasodilation.

PMID- 24729231
TI  - Development of a near infrared multi-wavelength, multi-channel, time-resolved
      spectrometer for measuring brain tissue haemodynamics and metabolism.
AB  - We present a novel time domain functional near infrared spectroscopy system using
      a supercontinuum laser allowing us to measure the coefficient of absorption and
      scattering of up to 16 multiplexed wavelengths in the near infrared region. This
      is a four detector system that generates up to 3 mW of light for each wavelength
      with a narrow 2-3 nm FWHM bandwidth between 650 and 890 nm; each measurement of
      16 wavelengths per channel can be performed up to a rate of 1 Hz. We can
      therefore quantify absolute haemoglobin changes in tissue and are currently
      investigating which and how many wavelengths are needed to resolve additional
      chromophores in tissue, such as water and the oxidation state of cytochrome-c
      oxidase. 

PMID- 24729232
TI  - Simulating NIRS and MRS measurements during cerebral hypoxia-ischaemia in piglets
      using a computational model.
AB  - We present a group analysis of the changes in cerebral haemodynamics, and the
      oxidation state of cytochrome-c-oxidase measured using broadband near-infrared
      spectroscopy (NIRS) and intracellular pH measured by phosphorous ((31)P) magnetic
      resonance spectroscopy (MRS) during and after cerebral hypoxia-ischaemia (HI) in
      15 piglets. We use a previously published computational model of cerebral
      metabolism in the piglet [1] to integrate these measurements and simulate HI. We
      successfully simulate changes in cellular metabolism including shifts in
      intracellular pH observed in the piglet brain during HI. In this process, we
      optimise physiological parameters in the model identified through sensitivity
      analysis (such as the rate of glucose metabolism and intracellular lactate
      concentration), to fit simulated and measured data. The model fits the data
      reasonably and suggests a 20 % drop in glucose consumption, a ~65 % increase in
      lactate concentration and ~35 % drop in the cerebral metabolic rate of oxygen
      (CMRO2) during HI.

PMID- 24729233
TI  - Analysis of slow wave oscillations in cerebral haemodynamics and metabolism
      following subarachnoid haemorrhage.
AB  - Aneurysmal subarachnoid haemorrhage (SAH) causes the greatest loss of productive
      life years of any form of stroke. Emerging concepts of pathophysiology highlight
      early abnormalities of microvascular function, including impaired autoregulation
      of cerebral blood flow and flow-metabolism coupling, as key causes of cerebral
      ischaemia and poor outcome. Near infrared spectroscopy (NIRS) is a non-invasive
      optical technique which may help identify cerebral microvascular dysfunction. The
      aim of this research is to investigate the status of flow-metabolism coupling by
      examining phase relationships between NIRS-derived concentrations of oxy
      haemoglobin ([HbO2]), deoxy-haemoglobin ([HHb]) and cytochrome c oxidase
      oxidation ([oxCCO]). Eight sedated ventilated patients with SAH were
      investigated. A combined NIRS broadband and frequency domain spectroscopy system
      was used to measure [HbO2], [HHb] and [oxCCO] alongside other multimodal
      neuromonitoring. Wavelet analysis of phase relationships revealed antiphase
      [HbO2]-[oxCCO] and in-phase [HbO2]-[HHb] oscillations between 0.1Hz-0.01Hz
      consistent with compromised flow-metabolism coupling. NIRS derived variables
      might offer unique insights into microvascular and metabolic dysfunction
      following SAH, and in the future identify therapeutic windows or targets.

PMID- 24729234
TI  - Effects of enriched environment on hippocampal neuronal cell death and
      neurogenesis in rat global ischemia.
AB  - Enriched environments reportedly show neuroprotective effects. Here, we evaluated
      the effect of an enriched environment prior to cerebral ischemia on neuronal cell
      death and neurogenesis in rats. Male SD rats were housed under standard
      conditions (SC) or in an enriched environment (EE), then subjected to global
      ischemia. The Y-maze test and novel object cognition test were used to evaluate
      cognitive function before and after ischemia. At 7 days post-ischemia, we
      evaluated hippocampal neuronal cell death with Fluoro-Jade B staining and
      neurogenesis with BrdU staining. Phosphorylated cAMP response element-binding
      protein (phospho-CREB) was also evaluated immunohistochemically. The EE +
      ischemia group showed a significant decrease of cell death post-ischemia compared
      with the SC + ischemia group. There was no difference in neurogenesis post
      ischemia between SC + ischemia and EE + ischemia. The EE + ischemia group showed
      a significant increase of performance before and after ischemia compared with the
      SC + ischemia group. Phospho-CREB-positive cells were significantly increased
      post-ischemia in EE + ischemia compared with SC + ischemia. EE suppressed
      hippocampal cell death due to global ischemia. Additionally, enhancement of
      cognitive function before and after ischemia and prevention of cognitive
      impairment associated with ischemia were observed compared with the controls
      (rats housed in SC without ischemia). The CREB pathway may play an important role
      in protection of cognitive ability. 

PMID- 24729235
TI  - Automated image analysis for diameters and branching points of cerebral
      penetrating arteries and veins captured with two-photon microscopy.
AB  - The present study was aimed to characterize 3-dimensional (3D) morphology of the
      cortical microvasculature (e.g., penetrating artery and emerging vein), using two
      photon microscopy and automated analysis for their cross-sectional diameters and
      branching positions in the mouse cortex. We observed that both artery and vein
      had variable cross-sectional diameters across cortical depths. The mean diameter
      was similar for both artery (17 +/- 5 MUm) and vein (15 +/- 5 MUm), and there
      were no detectable differences over depths of 50-400 MUm. On the other hand, the
      number of branches was slightly increased up to 400-MUm depth for both the artery
      and vein. The mean number of branches per 0.1 mm vessel length was 1.7 +/- 1.2
      and 3.8 +/- 1.6 for the artery and vein, respectively. This method allows for
      quantification of the large volume data of microvascular images captured with two
      photon microscopy. This will contribute to the morphometric analysis of the
      cortical microvasculature in functioning brains. 

PMID- 24729236
TI  - Cerebral hemodynamic change and metabolic alteration in severe hemorrhagic shock.
AB  - Understanding the biological mechanism and identifying biomarkers of hemorrhagic
      shock is important for diagnosis and treatment. We aim to use optical imaging to
      study how the cerebral blood circulation and metabolism change during the
      progression of severe hemorrhagic shock, especially the decompensatory stage. We
      used a multi-parameter (blood pressure (BP), cerebral blood flow (CBF),
      functional vascular density (FVD), blood oxygenation and mitochondrial NADH
      signal) cerebral cortex optical imaging system to observe brain hemodynamic
      change and metabolic alteration of rats in vivo for 4 h. Cerebral circulation and
      mitochondrial metabolism could be well preserved in the compensatory stage but
      impaired during the decompensatory stage. The changes of brain hemodynamics and
      metabolism may provide sensitive indicators for various shock stages including
      the transition from compensatory stage to decompensatory stage. Our novel imaging
      observations of hemodynamic and metabolic signals in vivo indicated that the rat
      brains under hemorrhagic shock suffered irreversible damage which could not be
      compensated by the autoregulation mechanism, probably due to injured
      mitochondria. 

PMID- 24729237
TI  - Physiological mechanism of increase in deoxy-hemoglobin concentration during
      neuronal activation in patients with cerebral ischemia: a simulation study with
      the balloon model.
AB  - Patients with cerebral ischemia or brain tumor have been reported to exhibit an
      increase of deoxygenated hemoglobin (deoxy-Hb) together with an increase of
      oxygenated hemoglobin (oxy-Hb). However, the physiological mechanisms underlying
      this hemodynamic response pattern are unclear. In this study, we performed a
      simulation using the balloon model (Buxton et al., Magn Reson Med 39:855-864,
      1998). We hypothesized that the oxygen extraction rate during the rest period (E
      0) in the patients is larger than in normal subjects, because the cerebral blood
      flow and the speed at which the blood passes through the brain tissues are lower
      in the patients. The simulation result showed an increase of deoxy-Hb as well as
      oxy-Hb, especially when E 0 is extremely high. Thus, the results of our
      simulation suggest that the increase of deoxy-Hb during activation in patients
      with ischemia or brain tumor is caused by an increased oxygen extraction rate at
      rest, compared with that of healthy adults. 

PMID- 24729238
TI  - Effect of blood in the cerebrospinal fluid on the accuracy of cerebral
      oxygenation measured by near infrared spectroscopy.
AB  - Near infrared spectroscopy (NIRS) is an optical technique used to examine the
      oxygenation state of tissues such as the brain in patients, including those with
      brain injury. We have examined the effect of a cerebrospinal fluid (CSF)
      contaminant, specifically haemoglobin, on the sensitivity of cerebral NIRS
      signals through computer simulation. Previous models of light transport in the
      head have shown that the clear CSF layer has a profound effect on the sensitivity
      profile of the NIRS signal due to its low absorbing, low scattering qualities. In
      subarachnoid haemorrhage, which may accompany brain injury, the principal near
      infrared chromophore, haemoglobin, is released into the CSF. Sensitivity was
      measured through forward modeling and the presence of haemoglobin within the CSF
      was modeled by increasing the absorption coefficient of the layer, with
      sensitivity quantified in terms of the partial pathlength of light within the
      brain. The model demonstrated that increases in the CSF absorption led to a
      marked decrease in the sensitivity to changes in the brain layer. This suggests
      that blood or other contaminants in the CSF may have a significant effect on the
      utility of NIRS for measurement of cerebral oxygenation, and merits further
      investigation. 

PMID- 24729239
TI  - Vessel specific imaging of glucose transfer with fluorescent glucose analogue in
      anesthetized mouse cortex.
AB  - The present study examined glucose transfer in the cellular scale of mouse brain
      microvasculature in vivo using two-photon microscopy and fluorescent glucose
      analogue (2-NBDG). The 2-NBDG was intravenously injected (0.04 mL/min) in the
      anesthetized Tie2-GFP mice in which the vascular endothelium expressed
      fluorescent protein. Time-lapse imaging was conducted on the cortical parenchyma,
      while the time-intensity change of the injected 2-NBDG was analysed in respective
      vascular compartments (artery, capillary, and vein). We observed that 2-NBDG
      signal increased monotonically in the vasculature during the period of the
      injection, and rapidly declined following its cessation. In tissue compartment,
      however, the signal intensity gradually increased even after cessation of the
      injection. Spatiotemporal analysis of the 2-NBDG intensity over the cross
      sections of the vessels further showed distinct change of the 2-NBDG intensity
      across the vessel wall (endothelium), which may represents a regulation site of
      tissue glucose influx. 

PMID- 24729240
TI  - Ischemic pretreatment delays ischemic brain vasospasm injury in gerbils.
AB  - Three experiments were conducted for the present study. First, to elucidate the
      mechanism and functional significance underlying ischemic vasoconstriction, we
      investigated the relationship between arteriolar constriction and tissue energy
      metabolism during bilateral common carotid artery occlusion in gerbils. Second,
      to identify differences in the postischemic recovery of physiologic parameters
      between short and prolonged brain ischemia, we measured changes in regional
      cerebral blood flow, microvessel diameter, brain temperature, and
      electrophysiologic response. Third, to explore the physiological mechanism of
      ischemic tolerance, we studied vascular response and intracerebral oxygenation
      states after acute global ischemia with and without pretreatment by mild ischemic
      stress. Here, we identify one of the physiologic mechanisms of the ischemic
      tolerance caused by brief ischemic pretreatment. 

PMID- 24729241
TI  - Changes in cerebral blood oxygenation induced by active standing test in children
      with POTS and NMS.
AB  - Orthostatic dysregulation (OD) has been classified into subtypes by heart rate
      and blood pressure; however, the hemodynamics of brains have not yet been
      revealed. Therefore, we investigated changes in cerebral blood flow and
      oxygenation during an active standing test to clarify the pathophysiology of two
      subtypes: postural tachycardia syndrome (POTS) and neurally mediated syncope
      (NMS). We studied 31 children (15 boys, 16 girls; mean age, 14.0 +/- 1.7 years)
      who presented with OD at the Department of Pediatrics and Child Health, Nihon
      University School of Medicine between 2009 and 2011. OD was diagnosed using the
      Japanese clinical guidelines for juvenile orthostatic dysregulation. After a 10
      min resting period in the supine position, patients were asked to quickly stand
      up and keep upright for 10 min. Cerebral blood flow and cerebral oxygenation were
      measured using transcranial Doppler sonography and near-infrared spectroscopy.
      POTS showed a significant decrease of oxy-Hb and resistance index (RI),
      suggesting transient ischemia with maintainable cerebral autoregulation. NMS
      showed a decrease of oxy-Hb and an increase of RI, suggesting ischemia and
      impairment of autoregulation. 

PMID- 24729243
TI  - Asymmetrical changes in cerebral blood oxygenation induced by an active standing
      test in children with postural tachycardia syndrome.
AB  - Near-infrared spectroscopy enables recognition of various brain conditions based
      on certain factors, such as oxygenated hemoglobin (oxy-Hb). Since July 2012, we
      have been trying to determine the mechanisms of autonomic function in Japanese
      children with orthostatic intolerance (also called orthostatic dysregulation) in
      Nihon University Itabashi Hospital in Tokyo, Japan. A total of 23 children aged 7
      16 years diagnosed with postural tachycardia syndrome (POTS), a subtype of
      orthostatic dysregulation, were enrolled in the study. We evaluated the relation
      between asymmetry in frontal cortex activity and the automatic nervous system and
      compared oxy-Hb changes in the right and left frontal cortices during an active
      standing test. We observed that during active standing oxy-Hb decreased in the
      frontal cortex. The oxy-Hb changes were asymmetrical, with a significantly larger
      decrease in the left frontal cortex than in the right frontal cortex, suggesting
      that tachycardia during active standing in POTS patients might be caused by
      activation of the right frontal cortex, which induces sympathetic nervous system
      activity. 

PMID- 24729242
TI  - Optical imaging of brain activation in Gambian infants.
AB  - We used optical topography (OT) to investigate cognitive function in infants in
      rural Gambia. Images of changes in oxyhaemoglobin and deoxyhaemoglobin
      concentrations were reconstructed using a multispectral algorithm which uses the
      finite element method (FEM) to model the propagation of light through scattering
      tissue using the diffusion equation. High quality OT data enabled us to
      reconstruct images with robust representation of haemodynamic changes. OT is a
      feasible neuroimage technology for this resource-poor setting. 

PMID- 24729244
TI  - Changes of cerebral tissue oxygen saturation at sleep transitions in adolescents.
AB  - In adults, cerebral oxy-([O2Hb]) and deoxyhemoglobin concentrations ([HHb])
      change characteristically at transitions of sleep stages. The aims were to assess
      these changes in adolescents and additionally to measure tissue oxygen saturation
      (StO2) by near infrared spectroscopy (NIRS). Previously it was reported that in
      adults [O2Hb] increased and [HHb] decreased at the transition from non-rapid eye
      movement sleep (NREMS) to REMS and wakefulness. Transitions to NREMS from
      REMS/wakefulness led to a decrease in [O2Hb] and an increase in [HHb]. We
      measured [O2Hb], [HHb] and tissue oxygenation (StO2) with NIRS approximately
      above the left prefrontal cortex in 12 healthy adolescent males (aged 10-16
      years). We found comparable signs and magnitudes of changes in [O2Hb] and [HHb]
      as observed in adults. StO2 increased at the transitions from NREMS to REMS and
      decreased from REMS to NREMS and at sleep onset (all p < 0.01, linear mixed
      effects model). Changes in oxygen metabolism during sleep transitions are similar
      in adolescents and adults. In addition, we show for the first time temporal
      changes of StO2 at sleep transitions.

PMID- 24729245
TI  - Influence of subjective happiness on the prefrontal brain activity: an fNIRS
      study.
AB  - Focusing on the relationship between subjective happiness (SH) and emotional
      changes, we examined influences of SH on emotion-related prefrontal activity
      using multichannel NIRS. The International Affective Picture System (IAPS) was
      used to evoke emotional changes. Subjects were a total of 18 right-handed healthy
      students. Frequency of picture-induced increases in oxygenated haemoglobin (oxy
      Hb) was evaluated. Subjects with a high SH score had a higher frequency of
      increased oxy-Hb in the left prefrontal cortex (PFC) while viewing pleasant
      pictures, whereas they showed a lower frequency in the right PFC while viewing
      unpleasant pictures. It is well known that the left PFC and right PFC are engaged
      in different ways in the emotional processes. Although further investigations are
      required, the present results indicate that the SH level influences the right
      left differences in emotion-related prefrontal activity. 

PMID- 24729246
TI  - Ginkobiloba extract improves working memory performance in middle-aged women:
      role of asymmetry of prefrontal cortex activity during a working memory task.
AB  - In order to clarify the mechanism through which extract of Ginkgo biloba leaves
      (EGb) improves cognitive function, we examined the effects of EGb on cerebral
      blood oxygenation in the prefrontal cortex (PFC) and on performance during a
      working memory task, using near-infrared spectrometry (NIRS). First, we evaluated
      differences in behavioral performance of the Sternberg working memory test (ST)
      and in the activation pattern of the PFC during ST between 15 young and 19 middle
      aged healthy women. Then, we examined the effect of EGb (120 mg/day for 6 weeks)
      on ST performance and PFC activation pattern in the middle-aged group. The middle
      aged group exhibited a longer reaction time (RT) in ST than the young group and
      showed a different PFC activation pattern during ST, i.e., the middle-aged group
      showed bilateral activation while the young group showed right-dominant
      activation. In the middle-aged group, administration of EGb for 6 weeks shortened
      the RT of ST and changed the PFC activation pattern to right-dominant, like that
      in the young group. The results indicate the PFC plays a role in the
      physiological cognitive function-enhancing effect of EGb. EGb might improve
      working memory function in middle-aged individuals by counteracting the
      occurrence of aging-related hemispheric asymmetry reduction. 

PMID- 24729247
TI  - Bayesian prediction of anxiety level in aged people at rest using 2-channel NIRS
      data from prefrontal cortex.
AB  - The aim of this study was to predict mental stress levels of aged people at rest
      from two-channel near-infrared spectroscopy (NIRS) data from the prefrontal
      cortex (PFC). We used the State-Trait Anxiety Inventory (STAI) for the mental
      stress index.We previously constructed a machine learning algorithm to predict
      mental stress level using two-channel NIRS data from the PFC in 19 subjects aged
      20-24 years at rest (Sato et al., Adv Exp Med Biol 765:251-256, 2013). In the
      present study, we attempted the same prediction for aged subjects aged 61-79
      years (10 women; 7 men). The mental stress index was again STAI. After subjects
      answered the STAI questionnaire, the NIRS device measured oxy- and deoxy
      hemoglobin concentration changes during a 3-min resting state. The algorithm was
      formulated within a Bayesian machine learning framework and implemented by Markov
      Chain Monte Carlo. Leave-one-subject-out cross-validation was performed.Average
      prediction error between the actual and predicted STAI values was 5.27.
      Prediction errors of 12 subjects were lower than 5.0. Since the STAI score ranged
      from 20 to 80, the algorithm appeared functional for aged subjects also. 

PMID- 24729248
TI  - Short-term hypoxic preconditioning improved survival following cardiac arrest and
      resuscitation in rats.
AB  - Cardiac arrest and resuscitation produces delayed mortality and hippocampal
      neuronal death in rats. Hypoxic preconditioning has been to shown to protect the
      brain from ischemic insults. We have previously reported that with chronic
      hypobaric hypoxia, the accumulation of hypoxic-inducible factor-1 alpha (HIF
      1alpha) and its target genes was increased for the first several days of hypoxic
      exposure, and returned to baseline level by 3 weeks when angiogenesis is
      completed. In this study, we investigated the effect of short-term (3 days) and
      long-term (21 days) hypoxic preconditioning on recovery from cardiac arrest and
      resuscitation in rats. Our data showed that the overall survival rate was
      considerably improved in the short-term hypoxic preconditioning group compared to
      the non-preconditioned controls (86 %, 6/7 vs. 54 %, 7/13); however, the survival
      rate in the long-term hypoxic preconditioning group was decreased. Our data
      suggest that hypoxic preconditioning provides protection after cardiac arrest and
      resuscitation more likely through increased accumulation of HIF-1alpha and its
      target genes rather than through successful vascular adaptation as a result of
      hypoxia-induced angiogenesis. 

PMID- 24729249
TI  - Venular valves and retrograde perfusion.
AB  - Forced retrograde perfusion through the venous system with arterial blood can
      provide adequate oxygen to peripheral tissues at rest through veno-capillary
      networks which is the basis for surgical restoration of blood flow by distal vein
      arterialization (DVA). To be successful such surgery requires disruption of valve
      leaflets in the veins, which can be accomplished easily in the larger vessels.
      However, the smallest veins (venules) of less than 100 MUm in diameter, also
      possess valves, are distributed widely throughout all tissues and are too fine
      for any effective surgical interference. Thus venular valves cannot be disrupted
      or dissected with presently available technology. Nevertheless, clinical
      observations suggest that retrograde peripheral blood flow is rapidly established
      after DVA surgery. There is as yet no rational explanation for this phenomenon.
      In the present study, using Laplace's law, we attempt to elucidate the mechanical
      properties of venules and their valves. We speculate that the remarkably thin
      venular walls (and especially those of the smaller vessels which have the
      thinnest walls), are capable of considerable, rapid distension when subjected to
      increased hemostatic pressure. The increase in diameter of venules in response to
      the increased blood pressure renders their valve leaflets incompetent, so that
      the valves themselves cannot close the vessel lumen. In addition, the thin
      bicuspid leaflets may also be forced open retrogradely by the increased blood
      pressure. 

PMID- 24729251
TI  - Use of NIRS to assess effect of training on peripheral muscle oxygenation changes
      in elite rugby players performing repeated supramaximal cycling tests.
AB  - In most team sports, intermittent high intensity sprint efforts combined with
      short recovery periods have been identified as a key factor of physical
      performance; the ability to repeat these efforts at a sustained level is of great
      importance. Near-infrared spectroscopy (NIRS) has been proposed as a tool to
      monitor muscle oxygenation changes during such sprint efforts. The purpose of
      this study was to observe muscle reoxygenation rate (reoxy rate) (% s-1) between
      sprint efforts in a repeat sprint cycle test. A two wavelength spatially resolved
      NIR spectrometer (Portamon, Artinis Inc.) was used to assess reoxy rate changes
      in the vastus lateralis of the dominant leg before and after a training stimulus.
      Eight UK premiership academy level rugby players were assessed (age 20.6 +/- 0.9)
      years; height 187 +/- 0.6 cm; weight 109.5 +/- 8.6 kg; quadriceps skin fold 16.6
      +/- 4.5 mm); the subjects completed ten repeated 10-s cycle sprints interspersed
      with 40 s recovery, upon a Wattbike Pro cycle. Hemoglobin variables (DeltaHHb,
      DeltatHb, DeltaO2Hb, DeltaTSI %) during the sprint and the post-sprint
      reoxygenation rate (%TSI s-1) were measured. During both cycle tests all subjects
      experienced a drop in muscle oxygen saturation (Pre-Delta - 12.39 +/- 6.01 %),
      Post-Delta - 14.83 +/- 3.88 %). Post-training, there was an increase in the
      extent of desaturation (drop in TSI %) in the group means, both for the biggest
      single change and the average of all ten changes. Seven out of eight players
      showed an increase based on the maximum change and six based on the average of
      their ten tests. Additionally, seven out of eight players showed a significant
      increase in DeltaHHb (Pre-Delta + 76.80 +/- 61.92, Post-Delta + 121.28 +/- 69.76)
      (p < 0.01) (including the one player who did not show a significant effect on the
      TSI measure). Players who exercised at the highest power tended to decrease their
      muscle oxygenation to a greater extent. The number of bike training sessions
      undertaken correlated with improvements in post-exercise recovery of oxygenation
      (R = 0.63). The simplest explanation for the increase in desaturation following
      training is an increase in muscle oxygen consumption due to an increase in
      mitochondrial content. This results in an increased extraction of delivered
      oxygen as confirmed by the HHb data. In conclusion, NIRS is able to measure
      positive training effects on muscle oxygen extraction, at the level of the
      individual elite athlete.

PMID- 24729250
TI  - Monitoring of filter patency during carotid artery stenting using near-infrared
      spectroscopy with high time-resolution.
AB  - We aimed to evaluate the usefulness of a newly developed, near-infrared
      spectroscopy (NIRS) device for monitoring hemodynamic changes during carotid
      artery stenting (CAS), as a means to detect filter obstruction due to distal
      embolism. We evaluated 16 patients with internal carotid artery (ICA) stenosis
      during the CAS procedure, using a NIRS system that can monitor not only changes
      in oxygenation of hemoglobin (Hb), but also the fluctuation of oxyhemoglobin (oxy
      Hb) synchronized with heartbeat. The NIRS system detected a marked decrease of
      oxy-Hb and an increase of deoxyhemoglobin (deoxy-Hb) during ICA occlusion in
      patients without anterior cross circulation (ACC). Patients with ACC showed much
      smaller changes. The analysis of oxy-Hb fluctuation made it possible to detect
      occurrence of no-flow in the absence of Hb concentration changes. The amplitude
      of oxy-Hb fluctuation in the no/slow-flow group was significantly smaller than
      that in the normal-flow group. Our results indicate that the present high time
      resolution NIRS device, which can measure oxy-Hb fluctuation, is superior to
      conventional NIRS for detecting filter obstruction. 

PMID- 24729252
TI  - Skeletal muscle deoxygenation responses during treadmill exercise in children.
AB  - Muscle O2 saturation (SmO2) and blood volume response in activating muscles
      during treadmill exercise were compared between prepubertal boys (n = 9, age: 9
      +/- 1 years) and young men (n = 9, age: 22 +/- 2 years). SmO2 and blood volume
      responses were monitored continuously during the exercise at the gastrocnemius
      medialis muscle by near infrared spatial resolved spectroscopy. SmO2 was
      significantly decreased only at peak exercise in the boys, even though a
      significant decrease in SmO2 was observed at 60, 80, and 100 % of peak O2 uptake
      in the men (p < 0.05). No significant increase in blood volume was observed in
      the boys, while blood volume was significantly increased in the men with
      increased exercise intensity (p < 0.05). These results suggest that both blood
      volume and deoxygenation response in activating muscle may be minor in
      prepubertal boys, compared to young men. The blunted deoxygenation response in
      prepubertal boys may be caused by undeveloped diffusive O2 transport (i.e.
      mitochondrial respiration).

PMID- 24729253
TI  - Development of a hybrid microwave-optical thermoregulation monitor for the
      muscle.
AB  - This paper presents the latest development of the hybrid microwave-optical
      thermoregulation monitor for the muscle. It is capable of warming the muscle and
      measuring the subsequent blood volume changes, using a novel microwave applicator
      with integrated optical probes. The challenge is to measure the thermoregulation
      response in deep tissue while minimizing any effect from the skin layer. We have
      introduced a skin cooling device, an additional integrated optical Laser Doppler
      flow monitoring probe and a temperature sensor to measure skin blood flow and
      temperature, respectively. The result shows that skin cooling is essential to
      minimize skin flow changes during microwave warming. The hybrid probe was placed
      on a human thigh to measure oxy/deoxy/total haemoglobin concentration changes
      (DeltaHbO2/DeltaHHb/DeltaHbT), skin flux and temperature upon microwave warming.
      Without skin cooling, the skin temperature was elevated by 4  degrees C and both
      DeltaHbO2/DeltaHbT and skin flux increased, showing microwave warming occurring
      in both the skin and muscle. With skin cooling, the skin temperature was kept
      relatively constant. While DeltaHbO2/DeltaHbT increased, the skin flux was
      relatively stable, showing a preferential microwave warming in the muscle, rather
      than the skin.

PMID- 24729254
TI  - Evaluation of a textile-based near infrared spectroscopy system in calf muscle
      oxygenation measurements.
AB  - We recently introduced a novel textile-based NIRS sensor (TexNIRS). Here, we
      evaluate TexNIRS in ten subjects (16 legs, age 28.5 +/- 2.32 years, adipose
      tissue thickness (ATT) 4.17 +/- 1.71 mm). Three venous occlusions at 50 mmHg were
      performed on their calf muscle. After 3 min of occlusion, oxy/deoxy hemoglobin
      concentration ([O2Hb], [HHb]) changes were 3.71 +/- 1.89/1.79 +/- 1.08 MUM;
      venous oxygen saturation (SvO2) was 75 +/- 9.7 %, oxygen consumption (VO2) was
      0.02 +/- 0.01 mL/100 g/min, hemoglobin flow (HF) was 0.93 +/- 0.48 MUmol/100
      mL/min, and blood flow (BF) was 2.01 +/- 1.04 mL/100 mL/min. Our results are in
      good agreement with the literature, but the TexNIRS enables a much higher level
      of comfort.

PMID- 24729255
TI  - Skin temperature in lower hind limb subjected to distal vein arterialization in
      rats.
AB  - Vascular surgery for distal vein arterialization (DVA) has been adopted
      clinically as a strategy for saving arteriosclerotic lower limbs from amputation.
      To gain more detailed information on DVA, the present study investigated the
      procedure in hind limbs of rats under isoflurane anesthesia. Since successful DVA
      requires destruction of venous valves, a coronary angioplasty catheter guidewire
      was used to destroy valves either solely in the femoral vein or in both femoral
      and popliteal veins. The femoral artery was then anastomosed to the femoral vein
      with sutures under binocular microsopic control. Changes in the distribution of
      skin blood flow in the hind limbs were studied with a thermal camera. Skin
      temperature increased in the thigh and knee after femoral venous valve
      destruction, but hyperthermia was observed in the distal leg and foot only when
      the valves in the popliteal vein were also disrupted. These results showed that
      increased arterial blood flow could be established by DVA surgery in both the
      proximal and distal regions of the hind limbs. 

PMID- 24729256
TI  - Epigenetic signature of chronic cerebral hypoperfusion and beneficial effects of
      S-adenosylmethionine in rats.
AB  - Chronic cerebral hypoperfusion is associated with cognitive decline in aging and
      age-related neurodegenerative disease. Epigenetic mechanisms are involved in the
      maintenance of long-term hypoxia-adapted cellular phenotypes. In the present
      study, the epigenetic signatures such as DNA methylation and histone acetylation,
      as well as S-adenosylmethionine (SAM) cycle using chronic cerebral hypoperfusion
      rat model were explored. Chronic cerebral hypoxia-induced global DNA
      hypermethylation associated with the increase of DNA methyltransferase (DNMT) 3A
      as well as alteration of SAM cycle. Meanwhile, an enhanced level of global
      histone H4 acetylation accompanied with the upregulation of histone
      acetyltransferase, p300/CREB-binding protein (CBP), and the downregulation of
      histone deacetylases (HDACs), was also observed. SAM could improve spatial
      capacity through the upregulation of acetylcholine and brain-derived neurotrophic
      factor (BDNF) rather than alteration of DNA methylation levels. In conclusion, we
      have demonstrated a genome-wide adjustment of DNA methylation and histone
      acetylation under chronic cerebral hypoxic conditions in a rat's brain. These
      epigenetic signatures may represent an additional mechanism to promote and
      maintain a hypoxic-adapted cellular responds with a potential role in memory
      deficits.

PMID- 24729263
TI  - How long to anticoagulate?

PMID- 24729264
TI  - Ruptured emphysematous infectious aortitis after endoprothesis placement.

PMID- 24729265
TI  - Powasson virus causing tick-borne encephalitis: a diagnostic dilemma.

PMID- 24729266
TI  - Trends in death attributed to myocardial infarction, heart failure and pulmonary
      embolism in Europe and Canada over the last decade.
AB  - BACKGROUND: Worldwide, cardiovascular diseases and cancer account for ~40% of
      deaths. Certain reports have shown a progressive decrease in mortality. Our main
      objective was to assess mortality trends related to myocardial infarction (MI),
      heart failure (HF) and pulmonary embolism (PE). METHODS: MI, HF and PE were
      studied as cause of death based on the analysis of death certificates in Canada
      (C), England and Wales (E), France (F) and Sweden (S). We also used a multiple
      cause approach. Age-standardized death rates (SDR) were calculated. RESULTS: The
      SDR for MI, HF or PE as the underlying cause of death, all decreased during the
      last decade. The decrease in SDR secondary to MI exceeded that for HF or PE.
      Concerning multiple cause of death, a greater decrease was also found for MI,
      compared with HF or PE. CONCLUSIONS: We confirm the beneficial trends in SDR with
      MI, HF or PE both as underlying or multiple causes in the studied countries. For
      HF and PE, multiple cause approach seems more accurate to describe the burden of
      these two pathologies. Our study also suggests that more efforts should be
      dedicated to HF and PE in order to achieve similar trends than in MI.

PMID- 24729267
TI  - Treatment of methemoglobinemia resulting in green urine.

PMID- 24729268
TI  - Urological evaluation of patients that had undergone in utero myelomeningocele
      closure: A prospective assessment at first presentation and early follow-up. Do
      their bladder benefit from it?
AB  - AIMS: To report our data on initial urological presentation after in utero
      myelomeningocele (MMC) closure. METHODS: A prospective urological assessment at
      first presentation was designed for patients that had undergone in utero MMC
      closure and referred to our urological facility. The protocol consisted of
      detailed medical history, renal sonography, voiding cystourethrogram, and
      urodynamic evaluation. RESULTS: In utero MMC closure was performed in 19 patients
      at gestational age of 25.6 weeks 25-27. Birth occurred at a mean gestational age
      of 31.8 weeks 26-36. Hyperactive bladder was observed in 89.5% 17/19. Bladder
      compliance was normal in two cases (10.5%), was markedly reduced in 10 patients
      (52.6%) and not possible to be determined due to urinary leakage in 7 patients
      (36.8%). We observed normal bladder capacity in 8 patients (42.1%), reduced in 11
      (57.9%), and detrusor-sphincter dyssynergia in 9 patients (47.4%). Underactive
      bladder was diagnosed in one case. Clean Intermittent Catheterization was
      initiated by 11 patients (57.9%) mostly in association with anticholinergics
      10/11. Vesicoureteral reflux was found in 5 patients (26.3%) and 9 had
      pyelonephritis at a mean follow-up of 5.4 months 2-17. CONCLUSIONS: Our data
      suggested that despite in utero MMC surgery, patients are at risk for bladder
      abnormal function and renal deterioration and should be aggressively treated, not
      differently from those operated in the post-natal term. This study has the merit
      of being a prospectively set evaluation performed by one investigator, including
      the urodynamic study. We acknowledge the need of long-term follow up.

PMID- 24729270
TI  - Three-phase hollow fiber liquid-phase microextraction based on a magnetofluid for
      the analysis of aristolochic acids in plasma by high-performance liquid
      chromatography.
AB  - A new and fast sample preparation technique based on three-phase hollow fiber
      liquid-phase microextraction with a magnetofluid was developed and successfully
      used to quantify the aristolochic acid I (AA-I) and AA-II in plasma after oral
      administration of Caulis akebiae extract. Analysis was accomplished by reversed
      phase high-performance liquid chromatography with fluorescence detection.
      Parameters that affect the hollow fiber liquid-phase microextraction processes,
      such as the solvent type, pH of donor and acceptor phases, content of
      magnetofluid, salt content, stirring speed, hollow fiber length, extraction
      temperature, and extraction time, were investigated and optimized. Under the
      optimized conditions, the preconcentration factors for AA-I and AA-II were >627.
      The calibration curve for two AAs was linear in the range of 0.1-10 ng/mL with
      the correlation coefficients >0.9997. The intraday and interday precision was
      <5.71% and the LODs were 11 pg/mL for AA-I and 13 pg/mL for AA-II (S/N = 3). The
      separation and determination of the two AAs in plasma after oral administration
      of C. akebiae extract were completed by the validated method. 

PMID- 24729269
TI  - BRCA1 point mutations in premenopausal breast cancer patients from Central Sudan.
AB  - Premenopausal breast cancer (BC) is one of the most common cancers of women in
      rural Africa and part of the disease load may be related to hereditary
      predisposition, including mutations in the BRCA1 gene. However, the BRCA1
      mutations associated with BC in Africa are scarcely characterized. We report here
      33 BRCA1 point mutations, among which 2 novel missense variants, found in 59
      Central Sudanese premenopausal BC patients. The high fractions of mutations with
      intercontinental and uniquely African distribution (17/33, 51.5 % and 14/33, 42.4
      %, respectively) are in agreement with the high genetic diversity expected in an
      African population. Overall 24/33 variants (72.7 %) resulted neutral; 8/33 of
      unknown significance (24.3 %, including the 2 novel missense mutations); 1 (3.0
      %) overtly deleterious. Notably, in silico studies predict that the novel C
      terminal missense variant c.5090G>A (p.Cys1697Tyr) affects phosphopeptide
      recognition by the BRCA1 BRCT1 domain and may have a pathogenic impact. Genetic
      variation and frequency of unique or rare mutations of uncertain clinical
      relevance pose significant challenges to BRCA1 testing in Sudan, as it might
      happen in other low-resource rural African contexts. 

PMID- 24729271
TI  - Population pharmacokinetics of hydroxyurea for children and adolescents with
      sickle cell disease.
AB  - The objective of this study was to develop a population pharmacokinetic (PK)
      model sufficient to describe hydroxyurea (HU) concentrations in serum and urine
      following oral drug administration in pediatric patients with sickle cell
      disease. Additionally, the measured hydroxyurea concentrations for particular
      sampling time were correlated with exposure measures (AUC) to find the most
      predictive relationship. Hydroxyurea concentrations were determined in 21
      subjects. Using a population nonlinear mixed-effect modeling, the HU PK was best
      described by a one-compartment model with two elimination pathways (metabolic and
      renal) and a transit compartment absorption. The typical mean absorption time was
      0.222 hour. The typical apparent volume of distribution was 21.8 L and the
      apparent systemic clearance was 6.88 L/h for an average weight patient of 30.7
      kg. The 50% of the HU dose was renally excreted. Linear correlations were
      apparent between the plasma HU concentration at 1, 1.5, 2, 4, and 6 hours post
      dose and AUC with the most significant (R(2)  = 0.71) observed at 1.5 hours. A
      population PK model was successful in describing HU disposition in plasma and
      urine. Data from the model also demonstrated that HU plasma concentrations at 1.5
      hours after an oral dose of the drug were highly predictive of systemic drug
      exposure. 

PMID- 24729272
TI  - A bubble-mediated intelligent microscale electrochemical device for single-step
      quantitative bioassays.
AB  - An intelligent microscale electrochemical device (iMED) for one-step,
      quantitative and multiplexed electrochemical detection of biomarkers for
      infectious diseases and tumors is developed. A "plug-in-cartridge" technology is
      introduced and adapted for use in screen-printed electrodes (SPEs) in
      electrochemical devices. Using this iMED, biomarkers for two types of tumors and
      one infectious disease are detected at sub-ng/mL levels in less than 30 min. 

PMID- 24729274
TI  - Sperm in the reproduction flea market .... how do they move that way?

PMID- 24729277
TI  - Antibodies against high-risk human papillomavirus proteins as markers for
      invasive cervical cancer.
AB  - Different human papillomavirus (HPV) genes are expressed during the various
      phases of the HPV life cycle and may elicit immune responses in the process
      towards malignancy. To evaluate their association with cervical cancer,
      antibodies against proteins from HPV16 (L1, E1, E2, E4, E6 and E7) and
      HPV18/31/33/35/45/52/58 (L1, E6 and E7) were measured in serum of 307 invasive
      cervical cancer cases and 327 controls from Algeria and India. Antibody response
      was evaluated using a glutathione S-transferase-based multiplex serology assay
      and HPV DNA detected from exfoliated cervical cells using a GP5+/6+-mediated PCR
      assay. Among HPV16 DNA-positive cases, seroprevalence of HPV16 antibodies ranged
      from 16% for HPV16 E1 to 50% for HPV16 E6 and all were significantly higher than
      controls. Seroprevalence of E6, E7 and L1 antibodies for HPV18 and for at least
      one of HPV31/33/35/45/52/58 were also higher in cases positive for DNA of the
      corresponding type (50% and 30% for E6 of HPV18 and HPV31/33/35/45/52/58
      combined, respectively). E6 and E7 antibodies were rarely found in controls, but
      cross-reactivity was evident among cancer cases positive for DNA of closely
      phylogenetically-related HPV types. E6 or E7 antibodies against any of the eight
      HPV types were detected in 66.1% of all cervical cancer cases, as compared to
      10.1% of controls. E6, and to a lesser extent E7, antibodies appear to be
      specific markers of HPV-related malignancy. However, even among cases positive
      for the same type of HPV DNA, approximately one-third of cervical cancer cases
      show no detectable immune response to either E6 or E7. 

PMID- 24729276
TI  - Self-assembling amphiphilic peptides.
AB  - The self-assembly of several classes of amphiphilic peptides is reviewed, and
      selected applications are discussed. We discuss recent work on the self-assembly
      of lipopeptides, surfactant-like peptides and amyloid peptides derived from the
      amyloid-beta peptide. The influence of environmental variables such as pH and
      temperature on aggregate nanostructure is discussed. Enzyme-induced remodelling
      due to peptide cleavage and nanostructure control through photocleavage or photo
      cross-linking are also considered. Lastly, selected applications of amphiphilic
      peptides in biomedicine and materials science are outlined.

PMID- 24729279
TI  - Non-thromboembolic risk in systemic lupus erythematosus associated with
      antiphospholipid syndrome.
AB  - OBJECTIVES: We investigated the impact of secondary antiphospholipid syndrome
      (APS) and antiphospholipid antibody (aPL) positivity on the non-thromboembolic
      clinical manifestations of systemic lupus erythematosus (SLE). METHODS: In total,
      224 patients with SLE were studied, of whom 105 were aPL-positive; 52 fulfilled
      the criteria for APS. SLE- and APS-related clinical and laboratory features were
      assesed: SLE patients with aPL or APS were compared with those without these
      features. RESULTS: Not only thromboembolic events, but also Coombs-positive
      haemolytic anaemia, thrombocytopenia and endocarditis occurred significantly more
      frequently in the aPL-positive than in the aPL-negative patients. In the APS +
      SLE subgroup, several non-thromboembolic symptoms occurred more often than in the
      absence of APS: pleuritis, interstitial lung disease, myocarditis, nephritis and
      organic brain syndrome. The mean number of major organ manifestations (1.2 vs.
      0.5) and the overall number of organ manifestations (8.1 vs. 6.9) were higher in
      the APS + SLE patients than in those without APS (p < 0.05). The APS + SLE
      subgroup more frequently required intensive immunosuppressive treatment than did
      the APS-negative patients (p < 0.05). CONCLUSIONS: SLE patients with aPL
      positivity or secondary APS also have a higher risk to develop non-thromboembolic
      disease manifestations in addition to the aPL-related symptoms, and are
      predisposed to more severe SLE manifestations.

PMID- 24729278
TI  - Comparison of renal response parameters for juvenile membranous plus
      proliferative lupus nephritis versus isolated proliferative lupus nephritis: a
      cross-sectional analysis of the CARRA Registry.
AB  - Lupus nephritis (LN) affects many patients with juvenile systemic lupus
      erythematosus (SLE) and is a significant cause of disease morbidity. Membranous
      plus proliferative LN (M + PLN) may represent a more difficult to treat subtype
      of juvenile LN, compared to isolated proliferative LN (PLN). In this
      retrospective observational study, we utilized data from the Childhood Arthritis
      and Rheumatism Research Alliance (CARRA) registry to compare response rates for
      pediatric M + PLN versus PLN. Response was assessed at the most recent CARRA
      registry visit gathered >=6 months after diagnostic kidney biopsy. Estimated
      glomerular filtration rate (GFR) less than 90 ml/min/1.73 m(2), indicating renal
      insufficiency, was found in 16.1% of patients with M + PLN and 6.1% of patients
      with PLN (P = 0.071). We found no significant difference in achievement of
      response in either hematuria or proteinuria between PLN and M + PLN groups or
      between subgroups determined by presence of class III vs. class IV proliferative
      disease. Exposure rates to mycophenolate, cyclophosphamide, and rituximab were
      similar between groups. Future studies will be necessary to correlate pediatric
      LN renal histology data with treatment response as well as other disease outcome
      measures. 

PMID- 24729280
TI  - Antiphospholipid antibodies in neonates with stroke--a unique entity or variant
      of antiphospholipid syndrome?
AB  - OBJECTIVE: YB current affiliation: Department of Pediatrics, Hadassah-Hebrew
      University Medical Center, Mount Scopus, Israel YB and MJS contributed equally to
      the study and should be regarded as joint first authors on this manuscript.
      Antiphospholipid syndrome (APS) may present with thrombosis and persistently
      elevated titers of antiphospholipid antibodies (aPL) in the neonatal period. Our
      aim was to investigate the course and impact of elevated titers of aPL in a
      cohort of infants presenting with either perinatal arterial ischemic stroke (PAS)
      or cerebral sinus vein thrombosis (CSVT) during the perinatal period. STUDY
      DESIGN: Sixty-two infants with clinically and radiologically confirmed PAS or
      CSVT presenting in the neonatal period underwent thrombophilia workup that
      included Factor V Leiden (FVL), PII20210A mutation, MTHFR 677T polymorphism,
      protein C, protein S, aPL namely either circulating lupus anticoagulant (CLA),
      anticardiolipin antibodies (aCL) or anti-beta2-glycoprotein-1 (beta2GP1). Mothers
      also underwent thrombophilia workup. RESULTS: Twelve infants with persistently
      elevated aPL were prospectively followed. Infants with positive aPL showed no
      concordance with presence of maternal aPL. All children were followed for a
      median of 3.5 years (range: nine months to 19 years) with repeated aPL testing
      every three to six months. Anticoagulant therapy initiation and therapy duration
      varied at the physician's discretion. In 10/12 cases aPL decreased to normal
      range within 2.5 years; one female with complex thrombophilia risk factors
      required indefinite prolonged anticoagulation. None of the infants showed
      recurrent thrombosis or any other APS manifestations, despite lack of prolonged
      anticoagulation. CONCLUSIONS: The presence of aPL may be important in the
      pathogenesis of cerebral thrombosis in neonates. Nevertheless, the nature of
      thrombophilia interactions in this period and their therapeutic impact warrants
      further investigation.

PMID- 24729281
TI  - Suffrutines A and B: a pair of Z/E isomeric indolizidine alkaloids from the roots
      of Flueggea suffruticosa.
AB  - Suffrutines A (1) and B (2), a pair of novel photochemical Z/E isomeric
      indolizidine alkaloids, with a unique and highly conjugated C20 skeleton, were
      isolated from the roots of Flueggea suffruticosa. The structures were elucidated
      by extensive analysis of NMR spectra and single-crystal X-ray diffraction. The
      light-induced isomerization and hypothetical biogenetic pathway to 1 and 2, as
      well as their activity for regulating the morphology of Neuro-2a cells are also
      discussed. 

PMID- 24729282
TI  - Stationary phases for the enrichment of glycoproteins and glycopeptides.
AB  - The analysis of protein glycosylation is important for biomedical and
      biopharmaceutical research. Recent advances in LC-MS analysis have enabled the
      identification of glycosylation sites, the characterisation of glycan structures
      and the identification and quantification of glycoproteins and glycopeptides.
      However, this type of analysis remains challenging due to the low abundance of
      glycopeptides in complex protein digests, the microheterogeneity at glycosylation
      sites, ion suppression effects and the competition for ionisation by co-eluting
      peptides. Specific sample preparation is necessary for comprehensive and site
      specific glycosylation analyses using MS. Therefore, researchers continue to
      pursue new columns to broaden their applications. The current manuscript covers
      recent literature published from 2008 to 2013. The stationary phases containing
      various chemical bonding methods or ligands immobilisation strategies on solid
      supports that selectively enrich N-linked or sialylated N-glycopeptides are
      categorised with either physical or chemical modes of binding. These categories
      include lectin affinity, hydrophilic interactions, boronate affinity, titanium
      dioxide affinity, hydrazide chemistry and other separation techniques. This
      review should aid in better understanding the syntheses and physicochemical
      properties of each type of stationary phases for enriching glycoproteins and
      glycopeptides. 

PMID- 24729283
TI  - Role of protein kinase C beta2 in relaxin-mediated inhibition of cardiac
      fibrosis.
AB  - INTRODUCTION: Relaxin is a pleiotropic hormone owing endogenous antifibrosis
      effect on numerous organs. We demonstrated relaxin's inhibitive effect on cardiac
      fibrosis previously. OBJECTIVE: The aim of this study was to investigate the role
      of protein kinase C (PKC) beta2 in relaxin's action under high glucose
      conditions. METHODS AND RESULTS: Cardiac fibroblasts (CFs) were isolated, exposed
      to high glucose and incubated with recombinant human relaxin (rhRLX). Western
      blot analysis revealed a relaxin-mediated decrease in total expression and
      translocation of PKCbeta2, showing downregulation of PKCbeta2 is involved in
      relaxin's action. Blocking PKCbeta2 pathway with ruboxistaurin accelerated rhRLX
      mediated inhibition in both proliferation of CFs and deposition of collagen.
      CONCLUSION: In conclusion, relaxin can inhibit high glucose-associated cardiac
      fibrosis partly through PKCbeta2 pathway. Further work should be done to fully
      understand intracellular mechanisms of relaxin's action to accelerate its
      clinical use.

PMID- 24729284
TI  - Variants of 11beta-hydroxysteroid dehydrogenase (HSD11B) gene type 1 and 2 in
      Chinese obese adolescents.
AB  - OBJECTIVE: To investigate the relationship between 11beta-hydroxysteroid
      dehydrogenase (HSD11B) gene type 1 and 2 and obesity in Chinese children.
      METHODS: A total of 400 obese and 200 healthy adolescents were enrolled as obese
      and control groups. Seven SNPs in HSD11B1 (rs4393158, rs2235543, rs10082248,
      rs10863782, rs2236903, rs2298930, rs4545339) and four variants in HSD11B2 gene
      (rs28934592, rs28934591, rs28934594 and rs28934593) were measured by automated
      platform MassArray. RESULTS: The rs28934592 in HSD11B2 and rs10863782 in HSD11B1
      were excluded as false positive or HWE P < 0.05. Moreover, one allele type was
      found in the other three locations of HSD11B2. The minor allele frequency of
      rs2235543 and rs10082248 was higher in patients than that in controls (P = 0.045,
      P = 0.041, respectively). The rs10082248, rs2298930 and rs4545339 were associated
      with the risk of obesity in the recessive model (P < 0.05, respectively).
      Moreover, the total cholesterol in patients with GG or AG genotype was
      significantly higher than that in patients with AA genotype in rs10082248. The
      rs4393158 was associated with the hypertension in log-additive model test (P =
      0.037), and glucose abnormal and hypercholesteremia in dominant model test (P <
      0.05, respectively), while the rs2235543 was associated with hypercholesteremia
      in overdominant model test (P = 0.017). CONCLUSIONS: The polymorphism of HSD11B1
      may be a cause of childhood obesity, or even associated with the complication of
      childhood obesity. However, variants of HSD11B2 may be not a cause of obesity.

PMID- 24729285
TI  - Indwelling bladder catheterisation as part of intraoperative and postoperative
      care for caesarean section.
AB  - BACKGROUND: Caesarean section (CS) is the most common obstetric surgical
      procedure, with more than one-third of pregnant women having lower-segment CS.
      Bladder evacuation is carried out as a preoperative procedure prior to CS.
      Emerging evidence suggests that omitting the use of urinary catheters during and
      after CS could reduce the associated increased risk of urinary tract infections
      (UTIs), catheter-associated pain/discomfort to the woman, and could lead to
      earlier ambulation and a shorter stay in hospital. OBJECTIVES: To assess the
      effectiveness and safety of indwelling bladder catheterisation for intraoperative
      and postoperative care in women undergoing CS. SEARCH METHODS: We searched the
      Cochrane Pregnancy and Childbirth Group's Trials Register (31 December 2013) and
      reference lists of retrieved studies. SELECTION CRITERIA: Randomised controlled
      trials (RCTs) comparing indwelling bladder catheter versus no catheter or bladder
      drainage in women undergoing CS (planned or emergency), regardless of the type of
      anaesthesia used. Quasi-randomised trials, cluster-randomised trials were not
      eligible for inclusion. Studies presented as abstracts were eligible for
      inclusion providing there was sufficient information to assess the study design
      and outcomes. DATA COLLECTION AND ANALYSIS: Two review authors independently
      assessed studies for eligibility and trial quality, and extracted data. Data were
      checked for accuracy. MAIN RESULTS: The search retrieved 16 studies (from 17
      reports). Ten studies were excluded and one study is awaiting assessment. We
      included five studies involving 1065 women (1090 recruited). The five included
      studies were at moderate risk of bias.Data relating to one of our primary
      outcomes (UTI) was reported in four studies but did not meet our definition of
      UTI (as prespecified in our protocol). The included studies did not report on our
      other primary outcome - intraoperative bladder injury (this outcome was not
      prespecified in our protocol). Two secondary outcomes were not reported in the
      included studies: need for postoperative analgesia and women's satisfaction. The
      included studies did provide limited data relating to this review's secondary
      outcomes. Indwelling bladder catheter versus no catheter - three studies (840
      women) Indwelling bladder catheterisation was associated with a reduced incidence
      of bladder distension (non-prespecified outcome) at the end of the operation
      (risk ratio (RR) 0.02, 95% confidence interval (CI) 0.00 to 0.35; one study, 420
      women) and fewer cases of retention of urine (RR 0.06, 95% CI 0.01 to 0.47; two
      studies, 420 women) or need for catheterisation (RR 0.03, 95% CI 0.01 to 0.16;
      three studies 840 participants). In contrast, indwelling bladder catheterisation
      was associated with a longer time to first voiding (mean difference (MD) 16.81
      hours, 95% CI 16.32 to 17.30; one study, 420 women) and more pain or discomfort
      due to catheterisation (and/or at first voiding) (average RR 10.47, 95% CI 4.71
      to 23.25, two studies, 420 women) although high levels of heterogeneity were
      observed. Similarly, compared to women in the 'no catheter' group, indwelling
      bladder catheterisation was associated with a longer time to ambulation (MD 4.34
      hours, 95% CI 1.37 to 7.31, three studies, 840 women) and a longer stay in
      hospital (MD 0.62 days, 95% CI 0.15 to 1.10, three studies, 840 women). However,
      high levels of heterogeneity were observed for these two outcomes and the results
      should be interpreted with caution.There was no difference in postpartum
      haemorrhage (PPH) due to uterine atony. There was also no difference in the
      incidence of UTI (as defined by trialists) between the indwelling bladder
      catheterisation and no catheterisation groups (two studies, 570 women). However,
      high levels of heterogeneity were observed for this non-prespecified outcome and
      results should be considered in this context. Indwelling bladder catheter versus
      bladder drainage - two studies (225 women)Two studies (225 women) compared the
      use of an indwelling bladder catheter versus bladder drainage. There was no
      difference between groups in terms of retention of urine following CS, length of
      hospital stay or the non-prespecified outcome of UTI (as defined by the
      trialist).There is some evidence (from one small study involving 50 women), that
      the need for catheterisation was reduced in the group of women with an indwelling
      bladder catheter (RR 0.04, 95% CI 0.00 to 0.70) compared to women in the bladder
      drainage group. Evidence from another small study (involving 175 women) suggests
      that women who had an indwelling bladder catheter had a longer time to ambulation
      (MD 0.90, 95% CI 0.25 to 1.55) compared to women who received bladder drainage.
      AUTHORS' CONCLUSIONS: This review includes limited evidence from five RCTs of
      moderate quality. The review's primary outcomes (bladder injury during operation
      and UTI), were either not reported or reported in a way not suitable for our
      analysis. The evidence in this review is based on some secondary outcomes, with
      heterogeneity present in some of the analyses. There is insufficient evidence to
      assess the routine use of indwelling bladder catheters in women undergoing CS.
      There is a need for more rigorous RCTs, with adequate sample sizes, standardised
      criteria for the diagnosis of UTI and other common outcomes.

PMID- 24729286
TI  - Proteomics and the eye.

PMID- 24729292
TI  - ERRATUM.

PMID- 24729293
TI  - Person-centric clinical trials: Ethical challenges in recruitment and data
      transparency for improved outcomes.
AB  - Practitioners participating in clinical studies are faced with a number of
      ethical issues related to recruitment, informed consent, handling and
      transparency of data. Practitioners educated in Good Clinical Practice, applying
      the philosophy of person-centricity within a network utilizing risk-based
      monitoring and remote data entry can provide the requisite infrastructure and
      oversight to support person-centric clinical studies. While "patient-centered"
      clinical studies allow for a broader clinical outcome perspective beyond the
      investigator, the person-centric approach, accounts for the comprehensiveness and
      complexity of how we make health and healthcare decisions. Augmenting person
      centricity with comparative effectiveness studies allow for the inclusion of
      individual data significantly contributing to the aggregation of multiple data
      sets about individuals and populations. This enables more powerful and personal
      analytics and care and everyone is afforded the opportunity and privilege to
      contribute to improve clinical outcomes and in controlling and containing costs.
      Policy and institutional investment in infrastructure are prerequisite to
      accommodate these opportunities, to minimize abuses, and provide pathways for
      analyzing alternative healthcare patterns. Data provided will be comprehensive
      and robust, representative of use, with safety data more easily discernible from
      persons with a known past medical and health history. 

PMID- 24729294
TI  - Graphene oxide coated capillary for the analysis of endocrine-disrupting
      chemicals by open-tubular capillary electrochromatography with amperometric
      detection.
AB  - A graphene oxide-coated capillary was fabricated by using 3
      aminopropyltriethoxysilane as the cross-linking agent. It was used for the
      separation and detection of three endocrine-disrupting chemicals, including
      bisphenol A, 4-nonylphenol, and 4-octylphenol by capillary electrochromatography.
      Due to the hydrophobicity, hydrogen bonding, and pi-pi interaction between
      graphene oxide and the analytes, the three analytes could be well separated in pH
      = 11.0, 20 mmol/L Na2 B4 O7 -NaOH/methanol mobile phase (50:50, v/v) within 950
      s. After preconcentration, the detection limits were 6.7 * 10(-10) , 3.3 * 10(-9)
      , and 6.7 * 10(-10)  mol/L (S/N = 3) for bisphenol A, nonylphenol, and
      octylphenol, respectively. The developed method was successfully applied to the
      determination of the above analytes in water samples. The satisfactory result
      demonstrated that the graphene oxide coated capillary used in capillary
      electrochromatography with amperometric detection was convenient to prepare,
      highly stable, and had good reproducibility. 

PMID- 24729295
TI  - Effect of experimental and sample factors on dehydration kinetics of mildronate
      dihydrate: mechanism of dehydration and determination of kinetic parameters.
AB  - The dehydration kinetics of mildronate dihydrate [3-(1,1,1-trimethylhydrazin-1
      ium-2-yl)propionate dihydrate] was analyzed in isothermal and nonisothermal
      modes. The particle size, sample preparation and storage, sample weight, nitrogen
      flow rate, relative humidity, and sample history were varied in order to evaluate
      the effect of these factors and to more accurately interpret the data obtained
      from such analysis. It was determined that comparable kinetic parameters can be
      obtained in both isothermal and nonisothermal mode. However, dehydration
      activation energy values obtained in nonisothermal mode showed variation with
      conversion degree because of different rate-limiting step energy at higher
      temperature. Moreover, carrying out experiments in this mode required
      consideration of additional experimental complications. Our study of the
      different sample and experimental factor effect revealed information about
      changes of the dehydration rate-limiting step energy, variable contribution from
      different rate limiting steps, as well as clarified the dehydration mechanism.
      Procedures for convenient and fast determination of dehydration kinetic
      parameters were offered.

PMID- 24729297
TI  - Prevention methods for pest control and their use in Poland.
AB  - Prevention methods can still be a cost-effective and efficient tool for pest
      control. Rational use of prevention methods is a feasible way to reduce
      dependency on chemical protection in agriculture. Costs, workload and farmers'
      awareness are key issues, however. In Poland, crop rotation is used as a method
      for pest control only to a limited extent owing to the high share of cereals in
      the crop structure. The choice of resistant varieties is satisfactory, but
      farmers should make use of qualified seed material more often. Liming is
      recommended on the majority of farms on account of widespread soil acidity.
      Favourable aspects as regards the prevention of pest development are biodiversity
      and the popularity of prevention cultivation techniques.

PMID- 24729298
TI  - A binuclear gold(I) complex with mixed bridging diphosphine and bis(N
      heterocyclic carbene) ligands shows favorable thiol reactivity and inhibits tumor
      growth and angiogenesis in vivo.
AB  - In the design of anticancer gold(I) complexes with high in vivo efficacy, tuning
      the thiol reactivity to achieve stability towards blood thiols yet maintaining
      the thiol reactivity to target cellular thioredoxin reductase (TrxR) is of
      pivotal importance. Herein we describe a dinuclear gold(I) complex (1-PF6)
      utilizing a bridging bis(N-heterocyclic carbene) ligand to attain thiol stability
      and a diphosphine ligand to keep appropriate thiol reactivity. Complex 1-PF6
      displays a favorable stability that allows it to inhibit TrxR activity without
      being attacked by blood thiols. In vivo studies reveal that 1-PF6 significantly
      inhibits tumor growth in mice bearing HeLa xenograft and mice bearing highly
      aggressive mouse B16-F10 melanoma. It inhibits angiogenesis in tumor models and
      inhibits sphere formation of cancer stem cells in vitro. Toxicology studies
      indicate that 1-PF6 does not show systemic anaphylaxis on guinea pigs and
      localized irritation on rabbits.

PMID- 24729299
TI  - Cryogel micromechanics unraveled by atomic force microscopy-based
      nanoindentation.
AB  - Cell-instructive physical characteristics of macroporous scaffolds, developed for
      tissue engineering applications, often remain difficult to assess. Here, an
      atomic force microscopy-based nanoindentation approach is adapted to quantify the
      local mechanical properties of biohybrid glycosaminoglycan-poly(ethylene glycol)
      cryogels. Resulting from cryoconcentration effects upon gel formation, cryogel
      struts are observed to feature a higher stiffness compared to the corresponding
      bulk hydrogel materials. Local Young's moduli, porosity, and integral moduli of
      the cryogel scaffolds are compared in dependence on gel formation parameters. The
      results provide valuable insights into the cryogelation process and a base for
      adjusting physical characteristics of the obtained cryogel scaffolds, which can
      critically influence the cellular response. 

PMID- 24729300
TI  - Psychosocial and organizational work environment of nurse managers and self
      reported depressive symptoms: cross-sectional analysis from a cohort of nurse
      managers.
AB  - OBJECTIVES: The association between depressive symptoms and psycho-organisational
      work environment has been established in the literature. Some studies have
      evaluated depressive symptoms in healthcare workers, but little research has been
      carried out among nurse managers. The aim of the study is to evaluate the
      depressive symptoms prevalence among nurse managers' population and work
      environment factors. MATERIAL AND METHODS: A descriptive correlational research
      design was used. Data were collected from 296 nurse managers in five hospitals in
      the eastern area of France between 2007 and 2008. Health outcomes were evaluated
      by measuring depressive symptoms (CES-D scale), the exposure data by assessing
      psycho-organisational work environment with effort-reward imbalance-model of
      Siegrist. Multiple logistic regressions were used to describe the strength of the
      association between depressive symptoms and effort-reward imbalance adjusted for
      personal and occupational characteristics of the nurse managers. RESULTS: Among
      the nurse managers, a third had depressive symptoms, and 18% presented an effort
      reward imbalance (ratio: >= 1). A significant association was found between
      depressive symptoms and effort-reward imbalance (OR = 10.81, 95% CI: 5.1-23, p <
      10(-3)), and with esteem as a reward (OR = 3.21, 95% CI: 1.6-6.3, p < 10(-2)).
      CONCLUSION: In view of the hierarchical situation of nurse managers and their
      primary roles in hospitals, it is necessary to take prevention measures to
      improve their work environment and health.

PMID- 24729301
TI  - Lessons learned: from dye-sensitized solar cells to all-solid-state hybrid
      devices.
AB  - The field of solution-processed photovoltaic cells is currently in its second
      spring. The dye-sensitized solar cell is a widely studied and longstanding
      candidate for future energy generation. Recently, inorganic absorber-based
      devices have reached new record efficiencies, with the benefits of all-solid
      state devices. In this rapidly changing environment, this review sheds light on
      recent developments in all-solid-state solar cells in terms of electrode
      architecture, alternative sensitizers, and hole-transporting materials. These
      concepts are of general applicability to many next-generation device platforms. 

PMID- 24729302
TI  - The potential role of HIF on tumour progression and dissemination.
AB  - Cancer is the second cause of mortality worldwide, primarily owing to failure to
      cure metastatic disease. The need to target the metastatic process to reduce
      mortality is clear and research over the past decade has shown hypoxia-inducible
      factor-1 (HIF-1) to be one of the promising targets. In order for metastatic
      disease to be established, multiple steps need to be taken whereby the tumour
      cells escape into the bloodstream and survive, disseminate and then establish at
      a premetastatic niche. HIF-1 mediates hypoxia-induced proangiogenic factors such
      as vascular endothelial growth factor (VEGF) and platelet-derived growth factor
      (PDGF), which promote extravasation and chemotaxis. The migration of tumour cells
      is mediated by loss of E-cadherin, which results in a more invasive phenotype;
      dissemination of the tumour cells by increased vascular permeability and survival
      in the bloodstream through resistance to apoptosis as well as adhesion at the
      premetastatic niche are all controlled by factors under the influence of HIF-1.
      The overexpression of HIF in many aggressive cancer types as well as its role in
      the establishment of metastatic disease and treatment resistance demonstrate its
      potential target in therapeutics. Taken together, the role of HIF-1 in cancer and
      metastatic disease is clear and the need for better treatment targeting
      metastases is paramount; more aggressive phenotypes with less response to
      treatment are associated with HIF-1 expression. Our research has shown promise
      but many questions still remain to be answered. 

PMID- 24729303
TI  - Assessment of the urodynamic diagnosis in patients with urinary incontinence
      associated with normal pressure hydrocephalus.
AB  - AIMS: To assess the urodynamic patterns present in patients with adult normal
      pressure hydrocephalus (NPH) in our institution. METHODS: Retrospectively
      conducted study on patients diagnosed with NPH by the Neurosurgery Department of
      our institution, without etiological treatment or urogynecological disorders, who
      underwent an urodynamic study (UDS) performed according to methods proposed by
      the International Society of Continence (ICS). Clinical information,
      complementary tests and UDS were collected, and descriptive analysis was
      performed, with special focus in urodynamic final diagnosis. RESULTS: Eighty-one
      UDS performed between 2003 and 2013. Fifty-one Males (63%). Mean age: 74.89 +/-
      8.58 years old (range 52-88 years). Classical triad of symptoms: gait
      disturbance, dementia, and urinary incontinence (UI) presented in 48.1%. Urinary
      urgency in 80.9% and UI in 70%. In two cases (2.5%) UDS was not valuable.
      Urodynamic features of the 79 remaining studies revealed overactive detrusor (OD)
      in 56 patients (70.9%), being associated with Stress UI (SUI) in one case and
      with bladder outlet obstruction (BOO) in 19. SUI in six patients (7.6%) and BOO
      in five (6.3%). Detrusor underactivity in four cases (5%) and normal study in
      eight (10.1%). About 47.1% of males presented BOO. Cerebrospinal fluid shunt
      surgery was performed on 32 patients during follow-up, with subsequent clinical
      improvement in 90.6% of them. CONCLUSIONS: OD was the most frequent diagnosis
      within UDS conducted on adult NPH patients in our institution, with BOO in an
      elevated percentage of them. Etiological treatment led to symptomatic improvement
      in most of patients.

PMID- 24729304
TI  - Identification of the proteomic variations of invasive relative to non-invasive
      non-functional pituitary adenomas.
AB  - The incomplete surgery section of invasive non-functional pituitary adenomas
      (NFPAs) carries the increased risks of complications and requires adjuvant
      radiotherapy and medications. It is necessary to clarify the molecular mechanisms
      and markers of invasiveness to guide the management of NFPA patients. The study
      aimed to proteomic variations of invasive and non-invasive NFPAs and sought the
      protein markers for invasive NFPAs. Invasive (n = 4) and non-invasive (n = 4)
      NFPA tissues were analyzed (n = 3-5/each tissue) with 2DE and PDQuest software.
      Twenty-four high-resolution 2DE gels were quantitatively compared to determine
      differentially expressed proteins (DEPs) between invasive and non-invasive NFPAs.
      Approximately 1200 protein spots were detected in each 2DE map, and 103
      differential spots (64 upregulated and 39 downregulated) were identified. Among
      those 103 differential spots, 57 DEPs (30 upregulated and 27 downregulated) were
      characterized with peptide mass fingerprint and MS/MS. Gene-ontology (GO) and
      ingenuity pathway analyses of those DEPs revealed pathway networks including
      mitochondrial dysfunction, oxidative stress, mitogen-activated protein kinase
      signaling abnormality, TR/RXR activation, proteolysis abnormality, ketogenesis
      and ketolysis, cyclin-dependent kinase C signaling abnormality, and amyloid
      processing that were significantly associated with invasive characteristics of
      invasive NFPA. Those data demonstrate that proteomic variations exist between
      invasive and non-invasive NFPAs. 2DE-based comparative proteomics is an effective
      approach to identify proteomic variations and pathway network variations. Those
      findings will serve as a basis to understand the molecular mechanisms of invasive
      NFPAs and to discover protein markers to effectively manage patients with
      invasive NFPAs. 

PMID- 24729306
TI  - Tunable organic hetero-patterns via molecule diffusion control.
AB  - A simple, scalable method is reported to fabricate ordered hetero-structures of
      organic materials using template-directed growth. The 3D extension of the
      structures is firstly determined by pre-pattern size and deposition amount, and
      can further be in situ tuned by annealing at appropriate temperature. 

PMID- 24729307
TI  - Effects of radiation on inherited sterility in the European grapevine moth
      (Lobesia botrana).
AB  - BACKGROUND: The sterile insect technique (SIT) is an alternative, environmentally
      friendly method for controlling insect pests. In the Lepidoptera, a low dose of
      gamma irradiation causes inherited sterility (SIT-IS), leading to full sterility
      in females but only partial sterility in males, which successfully compete with
      wild males for mates. This study examined the effect of a low radiation dose (150
      Gy) on the fitness parameters of male and female Lobesia botrana, a polyphagous
      and major pest of vineyards found in the Middle East, Europe and the Americas.
      RESULTS: Irradiation of the pupae did not affect their emergence rate, flight
      ability out of a cylinder, male response to sex pheromone in a field cage or male
      or female mating success. A major effect of irradiation was observed in the
      significantly reduced number of irradiated females' offspring reaching pupation,
      and as a consequence a limited number of F2 offspring. The effect of irradiation
      on male partial sterility (also called inherited sterility) was reflected in the
      male-biased sex ratio of F1 offspring of irradiated males, the reduced number of
      F1 offspring and the very low number of F2 descendants. CONCLUSION: This study
      demonstrates the feasibility of controlling L. botrana using SIT-IS. Adding this
      method to the arsenal of environmentally friendly tools to control this pest may
      assist in further reducing the use of insecticides on edible crops.

PMID- 24729308
TI  - Confined trisomy 8 mosaicism of meiotic origin: a rare cause of aneuploidy in
      childhood cancer.
AB  - Whether chromosome abnormalities observed in tumor cells may in some cases
      reflect low-grade somatic mosaicism for anomalies present already at zygote
      formation, rather than acquired somatic mutations, has for long remained a
      speculation. We here report a patient with Wilms tumor, where constitutional
      somatic mosaicism of trisomy 8 was detected in a previously healthy 2 1/2-year
      old boy. Single Nucleotide Polymorphism (SNP) array analysis of tumor tissue
      revealed a complex distribution of allele frequencies for chromosome 8 that could
      not be explained solely by mitotic events. Combined analysis of allele
      frequencies, chromosome banding, and fluorescence in situ hybridization revealed
      that the majority of tumor cells contained four copies of chromosome 8, with
      three distinct haplotypes at a 2:1:1 ratio. Because the patient had not been
      subject to organ transplantation, these findings indicated that the tumor
      karyotype evolved from a cell with trisomy 8 of meiotic origin, with subsequent
      somatic gain of one additional chromosome copy. Haplotype analysis was consistent
      with trisomy 8 through nondisjunction at meiosis I. Matched normal renal tissue
      or peripheral blood did not contain detectable amounts of cells with trisomy 8,
      consistent with the complete lack of mosaic trisomy 8 syndrome features in the
      patient. This case provides proof of principle for the hypothesis that tumor
      genotypes may in rare cases reflect meiotic rather than mitotic events, also in
      patients lacking syndromic features. (c) 2014 Wiley Periodicals, Inc. 

PMID- 24729309
TI  - The aspect ratio of nanoparticle assemblies and the spatial arrangement of
      ligands can be optimized to enhance the targeting of cancer cells.

PMID- 24729310
TI  - Protein aggregation and particle formation in prefilled glass syringes.
AB  - The stability of therapeutic proteins formulated in prefilled syringes (PFS) may
      be negatively impacted by the exposure of protein molecules to silicone oil-water
      interfaces and air-water interfaces. In addition, agitation, such as that
      experienced during transportation, may increase the detrimental effects (i.e.,
      protein aggregation and particle formation) of protein interactions with
      interfaces. In this study, surfactant-free formulations containing either a
      monoclonal antibody or lysozyme were incubated in PFS, where they were exposed to
      silicone oil-water interfaces (siliconized syringe walls), air-water interfaces
      (air bubbles), and agitation stress (occurring during end-over-end rotation).
      Using flow microscopy, particles (>=2 MUm diameter) were detected under all
      conditions. The highest particle concentrations were found in agitated,
      siliconized syringes containing an air bubble. The particles formed in this
      condition consisted of silicone oil droplets and aggregated protein, as well as
      agglomerates of protein aggregates and silicone oil. We propose an interfacial
      mechanism of particle generation in PFS in which capillary forces at the three
      phase (silicone oil-water-air) contact line remove silicone oil and gelled
      protein aggregates from the interface and transport them into the bulk. This
      mechanism explains the synergistic effects of silicone oil-water interfaces, air
      water interfaces, and agitation in the generation of particles in protein
      formulations.

PMID- 24729311
TI  - Huge left ventricular pseudoaneurysm rupture in an African young adult patient.
AB  - A pseudoaneurysm of the ventricle is formed when there is rupture of the
      myocardial wall with the discontinuity being roofed over by the pericardium and
      mural thrombus or fibrous tissue without myocardial elements. Cardiac
      pseudoaneurysm is a rare and a potentially life-threatening event. Early
      prophylactic surgical aneurysmectomy has been the treatment of choice. In this
      context, we report an unusual case of giant left ventricular pseudoaneurysm, as a
      result of unknown aetiology, appearing like a pulsatile mass, which was easily
      seen from the chest wall, in a young female, successfully treated with surgery. 

PMID- 24729312
TI  - Concurrent dual-scopic management of diaphragm disease.
AB  - With the increasing appliance of minimally invasive approaches in both thoracic
      and general surgery, more and more diaphragmatic conditions are being managed
      with laparoscopy or thoracoscopy. Which one is adopted depends on the disease,
      facility support and surgeon's preference. However, in difficult scenarios such
      as adhesions, uncertain tumour location or bulky herniated organs, addition of
      another approach could be beneficial. Here we describe 2 cases, one with
      metastatic tumours within the diaphragm and another with diaphragmatic hernia in
      which concurrent thoracoscopic and laparoscopic, so-called dual-scopic,
      management was performed. 

PMID- 24729313
TI  - Proteomic characterization of pediatric craniopharyngioma intracystic fluid by LC
      MS top-down/bottom-up integrated approaches.
AB  - The combination of top-down and bottom-up platforms was utilized for the LC-MS
      proteomic characterization of the intracystic fluid of adamantinomatous
      craniopharyngioma pediatric brain tumor disease. Proteins and peptides
      characterization was achieved by high-resolution LC-ESI-LTQ-Orbitrap-MS analysis
      while low-resolution LC-ESI-IT-MS was applied for the complete screening of the
      samples and the evaluation of the protein distribution within patients. Top-down
      analyses were applied to liquid/liquid extracted samples while bottom-up analyses
      were performed after trypsin digestion of both untreated and pretreated samples.
      The two proteomic approaches were complementary for the characterization of the
      proteome of craniopharyngioma intracystic fluid. Proteins and peptides involved
      in inflammation, mineralization processes and lipid transport were identified, in
      agreement with the calcium flecks, cholesterol granules and bone residues
      characteristic of this fluid. Apolipoprotein A-I, A-II, C-I and J, hemoglobin
      fragments, ubiquitin, alpha-2-HS-glycoprotein or fetuin A, alpha-1
      antichymotrypsin, vitamin D binding protein, and alpha-1-acid glycoprotein were
      characterized. These data could be relevant for the comprehension of the
      processes involved in the pathogenesis of the disease and the development of the
      cyst and could contribute to the individuation of therapeutic targets for the
      reduction of the cyst volume delaying and/or avoiding invasive surgical
      treatments. 

PMID- 24729314
TI  - The sodium channel beta1 subunit mediates outgrowth of neurite-like processes on
      breast cancer cells and promotes tumour growth and metastasis.
AB  - Voltage-gated Na(+) channels (VGSCs) are heteromeric proteins composed of pore
      forming alpha subunits and smaller beta subunits. The beta subunits are
      multifunctional channel modulators and are members of the immunoglobulin
      superfamily of cell adhesion molecules (CAMs). beta1, encoded by SCN1B, is best
      characterized in the central nervous system (CNS), where it plays a critical role
      in regulating electrical excitability, neurite outgrowth and migration during
      development. beta1 is also expressed in breast cancer (BCa) cell lines, where it
      regulates adhesion and migration in vitro. In the present study, we found that
      SCN1B mRNA/beta1 protein were up-regulated in BCa specimens, compared with normal
      breast tissue. beta1 upregulation substantially increased tumour growth and
      metastasis in a xenograft model of BCa. beta1 over-expression also increased
      vascularization and reduced apoptosis in the primary tumours, and beta1 over
      expressing tumour cells had an elongate morphology. In vitro, beta1 potentiated
      outgrowth of processes from BCa cells co-cultured with fibroblasts, via trans
      homophilic adhesion. beta1-mediated process outgrowth in BCa cells required the
      presence and activity of fyn kinase, and Na(+) current, thus replicating the
      mechanism by which beta1 regulates neurite outgrowth in CNS neurons. We conclude
      that when present in breast tumours, beta1 enhances pathological growth and
      cellular dissemination. This study is the first demonstration of a functional
      role for beta1 in tumour growth and metastasis in vivo. We propose that beta1
      warrants further study as a potential biomarker and targeting beta1-mediated
      adhesion interactions may have value as a novel anti-cancer therapy.

PMID- 24729335
TI  - The divergent synthesis of nitrogen heterocycles by rhodium(II)-catalyzed
      cycloadditions of 1-sulfonyl 1,2,3-triazoles with 1,3-dienes.
AB  - The first rhodium(II)-catalyzed aza-[4+3] cycloadditions of 1-sulfonyl 1,2,3
      triazoles with 1,3-dienes have been developed, and enable the efficient synthesis
      of highly functionalized 2,5-dihydroazepines from readily available precursors.
      In some cases, the reaction pathway could divert to formal aza-[3+2]
      cycloadditions, thus leading to 2,3-dihydropyrroles. In this context, the titled
      reaction represents a capable tool for the divergent synthesis of two types of
      synthetically valuable aza-heterocycles from common rhodium(II) iminocarbene
      intermediates. 

PMID- 24729336
TI  - Vitamin D and vitamin D analogues for preventing fractures in post-menopausal
      women and older men.
AB  - BACKGROUND: Vitamin D and related compounds have been used to prevent
      osteoporotic fractures in older people. This is the third update of a Cochrane
      review first published in 1996. OBJECTIVES: To determine the effects of vitamin D
      or related compounds, with or without calcium, for preventing fractures in post
      menopausal women and older men. SEARCH METHODS: We searched the Cochrane Bone,
      Joint and Muscle Trauma Group Specialised Register (to December 2012), the
      Cochrane Central Register of Controlled Trials (2012, Issue 12), MEDLINE (1966 to
      November Week 3 2012), EMBASE (1980 to 2012 Week 50), CINAHL (1982 to December
      2012), BIOSIS (1985 to 3 January 2013), Current Controlled Trials (December 2012)
      and reference lists of articles. SELECTION CRITERIA: Randomised or quasi
      randomised trials that compared vitamin D or related compounds, alone or with
      calcium, against placebo, no intervention or calcium alone, and that reported
      fracture outcomes in older people. The primary outcome was hip fracture. DATA
      COLLECTION AND ANALYSIS: Two authors independently assessed trial risk of
      selection bias and aspects of methodological quality, and extracted data. Data
      were pooled, where possible, using the fixed-effect model, or the random-effects
      model when heterogeneity between studies appeared substantial. MAIN RESULTS: We
      included 53 trials with a total of 91,791 participants. Thirty-one trials, with
      sample sizes ranging from 70 to 36,282 participants, examined vitamin D
      (including 25-hydroxy vitamin D) with or without calcium in the prevention of
      fractures in community, nursing home or hospital inpatient populations. Twelve of
      these 31 trials had participants with a mean or median age of 80 years or
      over.Another group of 22 smaller trials examined calcitriol or alfacalcidol (1
      alphahydroxyvitamin D3), mostly with participants who had established
      osteoporosis. These trials were carried out in the setting of institutional
      referral clinics or hospitals.In the assessment of risk of bias for random
      sequence generation, 21 trials (40%) were deemed to be at low risk, 28 trials
      (53%) at unclear risk and four trials at high risk (8%). For allocation
      concealment, 22 trials were at low risk (42%), 29 trials were at unclear risk
      (55%) and two trials were at high risk (4%).There is high quality evidence that
      vitamin D alone, in the formats and doses tested, is unlikely to be effective in
      preventing hip fracture (11 trials, 27,693 participants; risk ratio (RR) 1.12,
      95% confidence intervals (CI) 0.98 to 1.29) or any new fracture (15 trials,
      28,271 participants; RR 1.03, 95% CI 0.96 to 1.11).There is high quality evidence
      that vitamin D plus calcium results in a small reduction in hip fracture risk
      (nine trials, 49,853 participants; RR 0.84, 95% confidence interval (CI) 0.74 to
      0.96; P value 0.01). In low-risk populations (residents in the community: with an
      estimated eight hip fractures per 1000 per year), this equates to one fewer hip
      fracture per 1000 older adults per year (95% CI 0 to 2). In high risk populations
      (residents in institutions: with an estimated 54 hip fractures per 1000 per
      year), this equates to nine fewer hip fractures per 1000 older adults per year
      (95% CI 2 to 14). There is high quality evidence that vitamin D plus calcium is
      associated with a statistically significant reduction in incidence of new non
      vertebral fractures. However, there is only moderate quality evidence of an
      absence of a statistically significant preventive effect on clinical vertebral
      fractures. There is high quality evidence that vitamin D plus calcium reduces the
      risk of any type of fracture (10 trials, 49,976 participants; RR 0.95, 95% CI
      0.90 to 0.99).In terms of the results for adverse effects: mortality was not
      adversely affected by either vitamin D or vitamin D plus calcium supplementation
      (29 trials, 71,032 participants, RR 0.97, 95% CI 0.93 to 1.01). Hypercalcaemia,
      which was usually mild (2.6 to 2.8 mmol/L), was more common in people receiving
      vitamin D or an analogue, with or without calcium (21 trials, 17,124
      participants, RR 2.28, 95% CI 1.57 to 3.31), especially for calcitriol (four
      trials, 988 participants, RR 4.41, 95% CI 2.14 to 9.09), than in people receiving
      placebo or control. There was also a small increased risk of gastrointestinal
      symptoms (15 trials, 47,761 participants, RR 1.04, 95% CI 1.00 to 1.08),
      especially for calcium plus vitamin D (four trials, 40,524 participants, RR 1.05,
      95% CI 1.01 to 1.09), and a significant increase in renal disease (11 trials,
      46,548 participants, RR 1.16, 95% CI 1.02 to 1.33). Other systematic reviews have
      found an increased association of myocardial infarction with supplemental
      calcium; and evidence of increased myocardial infarction and stroke, but
      decreased cancer, with supplemental calcium plus vitamin D, without an overall
      effect on mortality. AUTHORS' CONCLUSIONS: Vitamin D alone is unlikely to prevent
      fractures in the doses and formulations tested so far in older people.
      Supplements of vitamin D and calcium may prevent hip or any type of fracture.
      There was a small but significant increase in gastrointestinal symptoms and renal
      disease associated with vitamin D and calcium. This review found that there was
      no increased risk of death from taking calcium and vitamin D.

PMID- 24729338
TI  - New light on prions: putative role of co-operation of PrPc and Abeta proteins in
      cognition.
AB  - A seminal article of Takahashi et al. reporting concomitant accumulation of
      cellular prion protein (PrPc) and beta-amyloid (Abeta) in dystrophic neurites,
      within neuritic plaques raised an exciting issue that is important for our
      understanding of mechanisms of neurodegeneration. The mentioned authors
      interpreted their findings rather cautiously, however since the time of their
      publication, several reports representing different approaches and methods have
      seemed to indicate that both proteins appear to co-operate more intrinsically
      than it could have been imagined earlier. The goal of the review is to sum up the
      accruing research data with special attention to evidence pointing to the co
      operative role of PrPc and Abeta in cognitive impairment. 

PMID- 24729339
TI  - Ultrastructural alterations of human cortical capillary basement membrane in
      human brain oedema.
AB  - The capillary basement membranes are examined in severe traumatic brain injuries,
      vascular malformation, congenital hydrocephalus and brain tumours. They exhibit
      homogeneous and nodular thickening, vacuolization, rarefaction, reduplication,
      and deposition of collagen fibers. Their average thickness varied according to
      the aetiology and severity of brain oedema. In moderate brain oedema the
      thickness ranged from 71.97 to 191.90 nm in width, and in patients with severe
      brain oedema it varied from 206.66 to 404.22 nm. The basement membrane complex
      appears apparently intact in moderate oedema, and shows glio-basal dissociation
      in severe oedema. In areas of highly increased cerebro-vascular permeability, the
      basement membrane shows matrix disorganization, reduplication, and bifurcations
      protruding toward the endothelial cells, and acting as abluminal transcapillary
      channels. In regions of total brain necrosis, its structural stability is lost
      showing loosening, dissolution and rupture. Basement membrane swelling is due to
      overhydration of its protein-complex glycoprotein matrix. The thickening,
      rarefaction and vacuolization are induced by the increased vacuolar and vesicular
      transendothelial transport. The degenerated basement membrane areas exhibit a
      finely granular precipitate interpreted as protein, proteoglycan, glycoprotein,
      and agrin degraded matrix. 

PMID- 24729340
TI  - Low prevalence of most frequent pathogenic variants of six PARK genes in sporadic
      Parkinson's disease.
AB  - Genetic variants that confer susceptibility to Parkinson's disease (PD) show
      unbalanced distribution among different populations; genetic predisposition to
      either familial or sporadic forms of PD in Mexican-mestizo population has not
      been comprehensively studied. The aim of the present study was to analyze genetic
      variants in six PARK genes in PD patients. In total 381 individuals (173
      patients, 208 controls) were genotyped for p.Gly2019Ser and p.Gly2385Arg variants
      of LRRK2. The p.Gly2019Ser variant was present in two patients and one healthy
      control; the p.Gly2385Arg variant was not found. In a subgroup of early-onset PD
      (EOPD), MLPA analysis was done for PARKIN (PARK2), PINK1 (PARK6), DJ-1 (PARK7),
      LRRK2 (PARK8), SNCA (PARK1/4) and ATP13A2 (PARK9). We found a heterozygous
      deletion of exon 2 in PARK2 in the youngest patient of the early-onset group, who
      showed limited response to antiparkinsonian therapy. Although the changes
      Gly2019Ser and Gly2385Arg of LRRK2 are associated with PD in different
      populations; they may be a rare cause of PD in our population. Novel population
      specific variants may underlie PD susceptibility in Mexican mestizos. Our study
      suggests that the heterozygous deletion of exon 2 in the PARK2 gene is a risk
      factor for EOPD. 

PMID- 24729341
TI  - Mutations in the exon 7 of Trp53 gene and the level of p53 protein in double
      transgenic mouse model of Alzheimer's disease.
AB  - Alzheimer's disease (AD) leads to generation of beta-amyloid (Abeta) in the
      brain. Alzheimer's disease model PS/APP mice show a markedly accelerated
      accumulation of Abeta, which may lead to apoptosis induction e.g. in cells
      expressing wild-type p53. The TP53 gene is found to be the most frequently
      mutated gene in human tumour cells. There is accumulating evidence pointing out
      to the contribution of oxidative stress and chronic inflammation in both AD and
      cancer. The purpose of this study was to analyze exon 7 mutations of the murine
      Trp53 gene and Abeta/A4 and p53 protein levels in PS/APP and control mice. The
      studies were performed on female double transgenic PS/APP mice and young adults
      (8-12 weeks old) and age-matched control mice. The Trp53 mutation analysis was
      carried out with the use of PCR and DNA sequencing. The Abeta/A4 and p53 levels
      were analyzed by Western blotting. The frequency of mutations was almost
      quadrupled in PS/APP mice (44%), compared to controls (14%). PS/APP mice with the
      A929T and A857G mutations had a similar p53 level. In cerebral gray matter of
      PS/APP mice the level of p53 positive correlated with the level of Abeta protein
      (RS = +0.700, p < 0.05). In younger control animals, the T854G mutation was
      related to p53 down-regulation, while in aging ones, G859A substitution was most
      likely associated with over-expression of p53. In silico protein analysis
      revealed a possibly substantial impact of all four mutations on p53 activity.
      Three mutations were in close proximity to zinc-coordinating cysteine residues.
      It seems that in PS/APP mice missense Trp53 exon 7 mutations may be associated
      with the degenerative process by changes of p53 protein function.

PMID- 24729342
TI  - Nigrostriatal pathway degeneration in rats after intraperitoneal administration
      of proteasome inhibitor MG-132.
AB  - The proteins' ubiquitination and their further degradation by proteasomes are
      crucial for cell cycle regulation, transcription and DNA replication,
      inflammatory response, and apoptosis. Proteasome inhibitors have recently become
      considered as a promising method in cancer and inflammatory disease therapy. In
      this study, utilizing the rat model, we try to establish the influence of
      proteasome inhibitor MG-132: (1) on the basis of spontaneous and evoked locomotor
      activity and (2) on the condition of nigrostriatal projections eight weeks after
      MG-132 intraperitoneal administration. We also discuss the current status of
      knowledge about intraperitoneal administration of MG-132, a laboratory method
      that is being used more and more. Our results revealed a lack of motor
      abnormalities, but significant loss (20%) of substantia nigra pars compacta
      dopaminergic neurons after systemic MG-132 administration. This loss was
      accompanied by a corresponding decrease (8%) of density of dopaminergic terminals
      in dorsolateral striatum. Moreover, evidence of very limited but ongoing fibre
      degeneration within the dorsal striatum suggests that MG-132 severely disturbed
      the nigrostriatal pathway. In summary, intraperitoneal application of proteasome
      inhibitor MG-132, despite the encouraging results of experimental treatment and
      prevention of many pathological processes, should be used with caution because of
      the potential adverse effects on the structure of the central nervous system,
      especially elements of the nigrostriatal pathway. 

PMID- 24729343
TI  - Electrospun nanofiber mat as a protector against the consequences of brain
      injury.
AB  - Traumatic/surgical brain injury can initiate a cascade of pathological changes
      that result, in the long run, in severe damage of brain parenchyma and
      encephalopathy. Excessive scarring can also interfere with brain function and the
      glial scar formed may hamper the restoration of damaged brain neural pathways. In
      this preliminary study we aimed to investigate the effect of dressing with an L
      lactide-caprolactone copolymer nanofiber net on brain wound healing and the fate
      of the formed glial scar. Our rat model of surgical brain injury (SBI) of the
      fronto-temporal region of the sensorimotor cortex imitates well the respective
      human neurosurgery situation. Brains derived from SBI rats with net-undressed
      wound showed massive neurodegeneration, entry of systemic inflammatory cells into
      the brain parenchyma and the astrogliosis due to massive glial scar formation.
      Dressing of the wound with the nanofiber net delayed and reduced the destructive
      phenomena. We observed also a reduction in the scar thickness. The observed
      modification of local inflammation and cicatrization suggest that nanofiber nets
      could be useful in human neurosurgery. 

PMID- 24729344
TI  - Sphingosine kinases modulate the secretion of amyloid beta precursor protein from
      SH-SY5Y neuroblastoma cells: the role of alpha-synuclein.
AB  - Sphingosine kinases (SphK 1&2) are involved in the regulation of cell survival,
      differentiation and neurotransmitter secretion. Current data suggest potential
      links between sphingolipid signalling, alpha-synuclein (ASN) and Alzheimer's
      disease (AD). Our aim was to investigate the possible role of SphKs and ASN in
      the regulation of the production and secretion of the amyloid beta precursor
      protein (APP). We have previously shown that ASN intensified the secretion and
      toxicity of amyloid beta (Abeta) to the point where it caused cell death. Our
      current results show that APP, the precursor protein for Abeta, is also
      influenced by ASN. The stable overexpression of wtASN in SH-SY5Y cells caused a
      three-fold, significant increase of the cellular APP level. This suggests that
      the influence of ASN on Abeta metabolism may actually occur at the level of APP
      protein rather than only through the changes of its cleavage into Abeta. To
      elucidate the mechanisms of APP modulation the cells were exposed to S1P and an
      SphK inhibitor (SKI). 72 h S1P treatment at 5 uM caused a nearly 50% reduction of
      the cellular APP signal. S1P also caused a tendency towards higher APP secretion,
      though the results were insignificant. The inhibition of SphKs decreased medium
      APP levels in a dose-dependent manner, reaching significance at 5 uM SKI with a
      correspondingly elevated intracellular level. Thus, it is reasonable to expect
      that in fact the influence of SphK activity on APP might be pro-secretory. This
      would also be in agreement with numerous articles on SphK-dependent secretion in
      the literature. The chronic nature of AD further suggests that subtle alterations
      in APP metabolism could have the potential to drive important changes in brain
      condition. 

PMID- 24729345
TI  - Differential expression of microRNA-210 in gliomas of variable cell origin and
      correlation between increased expression levels and disease progression in
      astrocytic tumours.
AB  - INTRODUCTION: The microRNA, miR-210, is frequently associated with hypoxia
      induction, and an increase in its levels is often correlated with poor prognosis
      in many solid tumours. The present study examines the levels of miR-210 in glioma
      tumours of multiple origins to determine if an association can be established
      with disease progression. MATERIAL AND METHODS: Tissue samples were acquired from
      normal brain tissue, oligodendroglial tumours and astrocytic tumours. The
      astrocytic tumours were further divided by grade: diffuse astrocytomas (WHO grade
      II), anaplastic astrocytomas (WHO grade III), and glioblastoma (WHO grade IV).
      The expression of miR-210 was examined by real-time quantitative RT-PCR. The
      correlation of the expression of miR-210 and astrocytic tumour grade was analyzed
      by the Spearman correlation test. RESULTS: MiR-210 presents a differential
      expression depending on the origin of the glioma. Oligodendroglial tumours
      exhibit a significantly reduced level of miR-210 as compared with normal brain
      tissue. In contrast, astrocytic tumours demonstrate significantly increased
      levels of miR-210. Furthermore, the expression of miR-210 is positively
      correlated with the grade of astrocytic tumour, in the following order: grade IV
      > grade III > grade II > normal brain tissue (p < 0.05). CONCLUSIONS: MiR-210
      levels can be potentially established as a biomarker for pathological diagnosis
      of malignant astrocytic tumour progression. In addition, the expression of miR
      210 can be utilized as an additional identification measure of glioma tumour
      origin.

PMID- 24729346
TI  - Clinical and neuroimaging correlation of movement disorders in multiple
      sclerosis: case series and review of the literature.
AB  - Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the
      central nervous system, in which movement disorders (MD) have been reported very
      rarely. Anatomopathological studies of MS indicate two main processes:
      inflammation and neurodegeneration. The occurrence of the movement disorders
      symptoms in MS revises the question of aetiology of these two diseases. During
      the 10 years of observation in our out-patient clinic and MS units we examined
      about 2500 patients with clinically definite MS diagnosed according to the
      revised McDonald's criteria. Only in 10 cases we found coexistence of MS and MD
      signs. Below we present rare cases of patients with coexistence of MS and chorea,
      pseudoathetosis, dystonia and parkinsonism. Searching for the strategic focal
      lesion in our case series showed demyelinating plaques placed in the thalamus
      most often. Detailed analysis of the clinical, pharmacological and neuroimaging
      correlations may help to explain the character of movement disorders in MS. 

PMID- 24729347
TI  - Does "cerebellar liponeurocytoma" always reflect an expected site? An unusual
      case with a review of the literature.
AB  - A rare tumour, cerebellar liponeurocytoma, is classified into glioneuronal
      tumours under the 2000 World Health Organization (WHO) classification of tumours
      of the central nervous system. The current 2007 WHO classification, therefore,
      assigns grade II to the cerebellar liponeurocytoma. Tumours are predominantly
      localized in cerebellar hemispheres, and the second most common location is the
      vermis. To date, approximately 40 reported cases of cerebellar and 10 cases of
      supratentorial intraventricular liponeurocytoma have been reported. In this
      report, an unusual case of cerebellar liponeurocytoma was presented with
      extracerebellar location. In the future tumour classification, it should be
      considered that liponeurocytomas are not restricted only to the cerebellum, but
      they are located in supratentorial areas as well. 

PMID- 24729348
TI  - Quantifying measurement uncertainty in full-scale compost piles using organic
      micro-pollutant concentrations.
AB  - Reductions in measurement uncertainty for organic micro-pollutant concentrations
      in full scale compost piles using comprehensive sampling and allowing
      equilibration time before sampling were quantified. Results showed that both
      application of a comprehensive sampling procedure (involving sample crushing) and
      allowing one week of equilibration time before sampling reduces measurement
      uncertainty by about 50%. Results further showed that for measurements carried
      out on samples collected using a comprehensive procedure, measurement uncertainty
      was associated exclusively with the analytic methods applied. Application of
      statistical analyses confirmed that these results were significant at the 95%
      confidence level. Overall implications of these results are (1) that it is
      possible to eliminate uncertainty associated with material inhomogeneity and (2)
      that in order to reduce uncertainty, sampling procedure is very important early
      in the composting process but less so later in the process. 

PMID- 24729350
TI  - Electronic properties of isosymmetric phase boundaries in highly strained Ca
      Doped BiFeO3.

PMID- 24729351
TI  - Distinct frequency dependent effects of whole-body vibration on non-fractured
      bone and fracture healing in mice.
AB  - Low-magnitude high-frequency vibration (LMHFV) provokes anabolic effects in non
      fractured bone; however, in fracture healing, inconsistent results were reported
      and optimum vibration conditions remain unidentified. Here, we investigated
      frequency dependent effects of LMHFV on fracture healing. Twelve-week-old, female
      C57BL/6 mice received a femur osteotomy stabilized using an external fixator. The
      mice received whole-body vibrations (20 min/day) with 0.3g peak-to-peak
      acceleration and a frequency of either 35 or 45 Hz. After 10 and 21 days, the
      osteotomized femurs and intact bones (contra-lateral femurs, lumbar spine) were
      evaluated using bending-testing, u-computed tomography, and histomorphometry. In
      non-fractured trabecular bone, vibration with 35 Hz significantly increased the
      relative amount of bone (+28%) and the trabecular number (+29%), whereas cortical
      bone was not influenced. LMHFV with 45 Hz failed to provoke anabolic effects in
      trabecular or cortical bone. Fracture healing was not significantly influenced by
      whole-body vibration with 35 Hz, whereas 45 Hz significantly reduced bone
      formation (-64%) and flexural rigidity (-34%) of the callus. Although the exact
      mechanisms remain open, our results suggest that small vibration setting changes
      could considerably influence LMHFV effects on bone formation in remodeling and
      repair, and even disrupt fracture healing, implicating caution when treating
      patients with impaired fracture healing.

PMID- 24729352
TI  - Non-target effects of two sunflower seed treatments on Orius insidiosus
      (Hemiptera: Anthocoridae).
AB  - BACKGROUND: Systemic insecticides used as seed treatments are generally
      considered to be safe for natural enemies. However, predatory insects may feed
      directly on plants or use plant products to supplement their diet. This study
      examined whether chlorantraniliprole or thiamethoxam might negatively impact
      Orius insidiosus (Say) (Hemiptera: Anthocoridae) when bugs utilize sunflowers
      grown from treated seed. RESULTS: When eggs of O. insidiosus were laid in the
      stems of treated sunflower seedlings (two-leaf stage), thiamethoxam reduced egg
      viability and the longevity of females hatching from these eggs, whereas
      chlorantraniliprole reduced female survival. Thiamethoxam, but not
      chlorantraniliprole, reduced female fertility in six-leaf-stage plants. Nymphs
      exposed to thiamethoxam-treated seedlings had reduced survival, delayed
      development and reduced fecundity as adults, relative to other treatments,
      whereas chlorantraniliprole delayed oviposition. Nymphs exposed to six-leaf-stage
      plants did not differ from controls in either treatment. Adults exposed to
      treated plants expressed no significant differences among treatments for any
      parameter evaluated for either plant growth stage. CONCLUSION: Thiamethoxam
      treatment on sunflower seeds caused lethal and sublethal effects on O.
      insidiosus, whereas chlorantraniliprole was not lethal to any life stage,
      although sublethal effects were evident. The nymphal stage was most susceptible,
      and insecticidal toxicity diminished with plant development.

PMID- 24729354
TI  - High prevalence of immunoglobulin light chain gene aberrations as revealed by
      FISH in multiple myeloma and MGUS.
AB  - Multiple myeloma (MM) is a malignant B-cell neoplasm characterized by an
      uncontrolled proliferation of aberrant plasma cells in the bone marrow.
      Chromosome aberrations in MM are complex and represent a hallmark of the disease,
      involving many chromosomes that are altered both numerically and structurally.
      Nearly half of the cases are nonhyperdiploid and show IGH translocations with the
      following partner genes: CCND1, FGFR3 and MMSET, MAF, MAFB, and CCND3. The
      remaining 50% are grouped into a hyperdiploid group that is characterized by
      multiple trisomies involving chromosomes 3, 5, 7, 9, 11, 15, 19, and 21. In this
      study, we analyzed the immunoglobulin light chain kappa (IGK, 2p12) and lambda
      (IGL, 22q11) loci in 150 cases, mostly with MM but in a few cases monoclonal
      gammopathy of undetermined significance (MGUS), without IGH translocations. We
      identified aberrations in 27% (= 40 patients) including rearrangements (12%),
      gains (12%), and deletions (4.6%). In 6 of 18 patients with IGK or/and IGL
      rearrangements, we detected a MYC rearrangement which suggests that MYC is the
      translocation partner in the majority of these cases.

PMID- 24729355
TI  - Thread-like supercapacitors based on one-step spun nanocomposite yarns.
AB  - Thread-like electronic devices have attracted great interest because of their
      potential applications in wearable electronics. To produce high-performance,
      thread-like supercapacitors, a mixture of stable dispersions of single-walled
      carbon nanotubes and conducting polyaniline nanowires are prepared. Then, the
      mixture is spun into flexible yarns with a polyvinyl alcohol outer sheath by a
      one-step spinning process. The composite yarns show excellent mechanical
      properties and high electrical conductivities after sufficient washing to remove
      surfactants. After applying a further coating layer of gel electrolyte, two
      flexible yarns are twisted together to form a thread-like supercapacitor. The
      supercapacitor based on these two yarns (SWCNTs and PAniNWs) possesses a much
      higher specific capacitance than that based only on pure SWCNTs yarns, making it
      an ideal energy-storage device for wearable electronics. 

PMID- 24729356
TI  - Identification of dynapenia in older adults through the use of grip strength t
      scores.
AB  - INTRODUCTION: The aim of this study was to generate reference values and t-scores
      (1.0-2.5 standard deviations below average) for grip strength for healthy young
      adults and to examine the utility of t-scores from this group for the
      identification of dynapenia in older adults. METHODS: Our investigation was a
      population-based, general community secondary analysis of cross-sectional grip
      strength data utilizing the NIH Toolbox Assessment norming sample. Participants
      consisted of community-dwelling adults, with age ranges of 20-40 years (n = 558)
      and 60-85 years (n = 390). The main outcome measure was grip strength using a
      Jamar plus dynamometer. RESULTS: Maximum grip strengths were consistent over the
      20-40-year age group [men 108.0 (SD 22.6) pounds, women 65.8 (SD 14.6) pounds].
      Comparison of older group grip strengths to those of the younger reference group
      revealed (depending on age strata) that 46.2-87.1% of older men and 50.0-82.4% of
      older women could be designated as dynapenic on the basis of t-scores.
      CONCLUSIONS: The use of reference value t-scores from younger adults is a
      promising method for determining dynapenia in older adults.

PMID- 24729357
TI  - Racial and ethnic differences in older adults with knee osteoarthritis.
AB  - OBJECTIVE: Knee osteoarthritis (OA) contributes significantly to disability in
      older individuals, and racial/ethnic minorities are disproportionately affected.
      The present study aimed to characterize differences in clinical and experimental
      pain, including pain inhibition, among older African American (AA) and non
      Hispanic white (NHW) subjects with knee OA. METHODS: AA and NHW subjects with
      knee OA (n = 267) completed clinical and functional pain assessments, including
      quantitative sensory testing (QST). We hypothesized that, when compared to NHW
      subjects, AA subjects would display 1) lower pain tolerance and higher ratings of
      heat-, mechanical-, and cold-induced pain, 2) greater temporal summation of pain,
      3) reduced pain inhibition, and 4) greater clinical pain and poorer function. In
      addition, we hypothesized that the findings from QST would significantly predict
      the severity of clinical pain within each race/ethnicity. RESULTS: AA subjects
      with knee OA displayed increased pain sensitivity, greater temporal summation,
      and reduced pain inhibition when compared to NHW subjects with knee OA. Moreover,
      AA subjects reported greater clinical pain and poorer function. Racial/ethnic
      differences in clinical pain became nonsignificant when the analyses were
      controlled for education and annual income, whereas differences in QST findings
      remained highly significant. Although the extent of pain inhibition predicted the
      severity of clinical pain in both groups, different QST measures were
      additionally predictive of clinical pain within each group. CONCLUSION: The
      results of this study establish that there are racial/ethnic differences in
      experimental and clinical pain and function in older individuals with knee OA.
      Our findings indicating that different QST measures were associated with clinical
      pain within the 2 racial/ethnic groups, whereas reduced pain inhibition was
      important in all participants, warrant further study in order to elucidate the
      common and group-specific pathophysiologic mechanisms contributing to clinical
      pain in OA.

PMID- 24729358
TI  - gWEGA: GPU-accelerated WEGA for molecular superposition and shape comparison.
AB  - Virtual screening of a large chemical library for drug lead identification
      requires searching/superimposing a large number of three-dimensional (3D)
      chemical structures. This article reports a graphic processing unit (GPU)
      accelerated weighted Gaussian algorithm (gWEGA) that expedites shape or shape
      feature similarity score-based virtual screening. With 86 GPU nodes (each node
      has one GPU card), gWEGA can screen 110 million conformations derived from an
      entire ZINC drug-like database with diverse antidiabetic agents as query
      structures within 2 s (i.e., screening more than 55 million conformations per
      second). The rapid screening speed was accomplished through the massive
      parallelization on multiple GPU nodes and rapid prescreening of 3D structures
      (based on their shape descriptors and pharmacophore feature compositions).

PMID- 24729378
TI  - Lack of Absent in Melanoma 2 (AIM2) expression in tumor cells is closely
      associated with poor survival in colorectal cancer patients.
AB  - Functional studies on colorectal cancer cells indicated a protective role of the
      interferon-inducible dsDNA sensor Absent in Melanoma 2 (AIM2) in cancer
      progression. Given that a high mutation rate and lack of AIM2 expression was
      previously detected in a subset of colorectal cancers, we here investigated the
      association of AIM2 expression in tumor cells and patient prognosis (5-year
      follow-up). A tissue microarray analysis of 476 matched tissue pairs (colorectal
      tumor and adjacent normal colon epithelium) was performed by two independent
      observers. Samples from 62 patients were excluded because of missing follow-up
      information or due to neo-adjuvant therapy before tissue sampling. Out of the
      remaining 414 tissue pairs, 279 (67.4%) displayed reduced AIM2 expression in
      cancer cells when compared to epithelial cells of their normal counterpart.
      Thirty-eight patients (9.18%) had completely lost AIM2 expression in tumor cells.
      After adjustment for sex, age, cancer stage, tumor site, tumor grade and
      chemotherapy, complete lack of AIM2 expression was associated with an up to 3
      fold increase in overall mortality (HR=2.40; 95% CI=1.44-3.99) and disease
      specific mortality (HR=3.14; 95% CI=1.75-5.65) in comparison to AIM2-positive
      tumor samples. Our results demonstrate that lack of AIM2 expression is closely
      associated with poor outcome in colorectal cancer. The data thus strongly
      substantiate a protective role of AIM2 against progression of colorectal tumors.
      Further studies are required to assess whether lack of AIM2 expression may be
      used as a biomarker for the identification of colorectal cancer patients with
      poor prognosis.

PMID- 24729379
TI  - Visible-light-induced formal [3+2] cycloaddition for pyrrole synthesis under
      metal-free conditions.
AB  - A photocatalytic formal [3+2] cycloaddition of 2H-azirines with alkynes has been
      achieved under irradiation by visible light in the presence of organic dye
      photocatalysts. This transformation provides efficient access to highly
      functionalized pyrroles in good yields and has been applied to the synthesis of
      drug analogues. A primary trial of photocascade catalysis merging energy transfer
      and redox neutral reactions was shown to be successful. 

PMID- 24729380
TI  - [Primary Prevention of Mental Disorders in Children of Mentally Ill Parents. The
      Kanu Programme "Canoe--Moving Jointly Forward"].
AB  - Children of parents who suffer from mental health disorders are more likely to
      develop mental disorders than children of parents not suffering from mental
      disorders. For children at risk, preventive strategies are hardly available and,
      if available, rarely supported by a scientific evaluation. "Kanu - Gemeinsam
      weiterkommen (canoe - moving jointly forward)" is a preventive strategy that was
      developed within a research project focusing on primary prevention in children
      who live in families with parents affected by mental disorders. The intervention
      is characterised by a multi-modular concept and was tested in the adult
      psychiatric setting. Preliminary results indicate a preventive impact of the
      intervention programme. 

PMID- 24729381
TI  - Salmonella colonies in a bone marrow film.

PMID- 24729382
TI  - Three-phase catalytic system of H2O, ionic liquid, and VOPO4-SiO2 solid acid for
      conversion of fructose to 5-hydroxymethylfurfural.
AB  - Efficient transformation of biomass-derived feedstocks to chemicals and fuels
      remains a daunting challenge in utilizing biomass as alternatives to fossil
      resources. A three-phase catalytic system, consisting of an aqueous phase, a
      hydrophobic ionic-liquid phase, and a solid-acid catalyst phase of nanostructured
      vanadium phosphate and mesostructured cellular foam (VPO-MCF), is developed for
      efficient conversion of biomass-derived fructose to 5-hydroxymethylfurfural
      (HMF). HMF is a promising, versatile building block for production of value-added
      chemicals and transportation fuels. The essence of this three-phase system lies
      in enabling the isolation of the solid-acid catalyst from the aqueous phase and
      regulation of its local environment by using a hydrophobic ionic liquid, 1-butyl
      3-methylimidazolium bis(trifluoromethylsulfonyl)imide ([BMIM][Tf2N]). This system
      significantly inhibits the side reactions of HMF with H2O and leads to 91 mol %
      selectivity to HMF at 89 % of fructose conversion. The unique three-phase
      catalytic system opens up an alternative avenue for making solid-acid catalyst
      systems with controlled and locally regulated microenvironment near catalytically
      active sites by using a hydrophobic ionic liquid.

PMID- 24729383
TI  - Controllable synthesis of hollow Si anode for long-cycle-life lithium-ion
      batteries.

PMID- 24729384
TI  - Planned home versus hospital care for preterm prelabour rupture of the membranes
      (PPROM) prior to 37 weeks' gestation.
AB  - BACKGROUND: Preterm prelabour rupture of membranes (PPROM) is associated with
      increased risk of maternal and neonatal morbidity and mortality. Women with PPROM
      have been predominantly managed in hospital. It is possible that selected women
      could be managed at home after a period of observation. The safety, cost and
      women's views about home management have not been established. OBJECTIVES: To
      assess the safety, cost and women's views about planned home versus hospital care
      for women with PPROM. SEARCH METHODS: We searched the Cochrane Pregnancy and
      Childbirth Group's Trials Register (31 July 2013) and the reference lists of all
      the identified articles. SELECTION CRITERIA: Randomised and quasi-randomised
      trials comparing planned home versus hospital management for women with PPROM
      before 37 weeks' gestation. DATA COLLECTION AND ANALYSIS: Two review authors
      independently assessed clinical trials for eligibility for inclusion, risk of
      bias, and carried out data extraction. MAIN RESULTS: We included two trials (116
      women) comparing planned home versus hospital management for PPROM. Overall, the
      number of included women in each trial was too small to allow adequate assessment
      of pre-specified outcomes. Investigators used strict inclusion criteria and in
      both studies relatively few of the women presenting with PPROM were eligible for
      inclusion. Women were monitored for 48 to 72 hours before randomisation.
      Perinatal mortality was reported in one trial and there was insufficient evidence
      to determine whether it differed between the two groups (risk ratio (RR) 1.93,
      95% confidence interval (CI) 0.19 to 20.05).  There was no evidence of
      differences between groups for serious neonatal morbidity, chorioamnionitis,
      gestational age at delivery, birthweight and admission to neonatal intensive
      care.There was no information on serious maternal morbidity or mortality. There
      was some evidence that women managed in hospital were more likely to be delivered
      by caesarean section (RR (random-effects) 0.28, 95% CI 0.07 to 1.15). However,
      results should be interpreted cautiously as there is moderate heterogeneity for
      this outcome (I2 = 35%). Mothers randomised to care at home spent approximately
      10 fewer days as inpatients (mean difference -9.60, 95% CI -14.59 to -4.61) and
      were more satisfied with their care. Furthermore, home care was associated with
      reduced costs. AUTHORS' CONCLUSIONS: The review included two relatively small
      studies that did not have sufficient statistical power to detect meaningful
      differences between groups. Future large and adequately powered randomised
      controlled trials are required to measure differences between groups for relevant
      pre-specified outcomes. Special attention should be given to the assessment of
      maternal satisfaction with care and cost analysis as they will have social and
      economic implications in both developed and developing countries.

PMID- 24729385
TI  - 14q deletions are associated with trisomy 12, NOTCH1 mutations and unmutated IGHV
      genes in chronic lymphocytic leukemia and small lymphocytic lymphoma.
AB  - Deletions of the long arm of chromosome 14 [del(14q)] are rare but recurrently
      observed in mature B-cell neoplasms, particularly in chronic lymphocytic leukemia
      (CLL). To further characterize this aberration, we studied 81 cases with
      del(14q): 54 of CLL and 27 of small lymphocytic lymphoma (SLL), the largest
      reported series to date. Using karyotype and fluorescence in situ hybridization
      (FISH), the most frequent additional abnormality was trisomy 12 (tri12), observed
      in 28/79 (35%) cases, followed by del13q14 (12/79, 15%), delTP53 (11/80, 14%)
      delATM (5/79, 6%), and del6q21 (3/76, 4%). IGHV genes were unmutated in 41/53
      (77%) patients, with a high frequency of IGHV1-69 (21/52, 40%). NOTCH1 gene was
      mutated in 14/45 (31%) patients. There was no significant difference in
      cytogenetic and molecular abnormalities between CLL and SLL. Investigations using
      FISH and SNP-array demonstrated the heterogeneous size of the 14q deletions.
      However, a group with the same del(14)(q24.1q32.33) was identified in 48% of
      cases. In this group, tri12 (P = 0.004) and NOTCH1 mutations (P = 0.02) were
      significantly more frequent than in the other patients. In CLL patients with
      del(14q), median treatment-free survival (TFS) was 27 months. In conclusion,
      del(14q) is associated with tri12 and with pejorative prognostic factors:
      unmutated IGHV genes (with over-representation of the IGHV1-69 repertoire),
      NOTCH1 mutations, and a short TFS.

PMID- 24729386
TI  - Modelling the effect of pyrethroid use intensity on mite population density for
      walnuts.
AB  - BACKGROUND: Published studies relating pyrethroid use and subsequent mite
      outbreaks have largely been based on laboratory and field experiments, with some
      inferring a result of increased miticide use. The present study derived a
      mathematical model proposed to quantify the effect of pyrethroid use intensity on
      mite population density. The model was validated against and parameterized with
      actual field-level pyrethroid and miticide use data from 1995 to 2009 for
      California walnuts, where the miticide use intensity was a proxy of the mite
      population density. RESULTS: The parameterized model was MI = 1.61 - 0.89 . exp(
      93.31PI) (RMSE = 0.13; R(2) = 0.69; P < 0.01), where PI and MI are the average
      pyrethroid and miticide use intensity in small intervals respectively. A three
      range scheme was presented to quantify pesticide applications based on the change
      rate of MI to PI. Specific for California walnuts, the PI range of 0-0.025 kg ha(
      1) was identified as the rapidly increasing range where MI increased vastly when
      PI increased. CONCLUSION: Results confirmed that more miticide was used,
      presumably to prevent or control mite resurgence when pyrethroids were applied, a
      practice that is not only costly but might be expected to aggravate mite
      resistance to miticides and increase risk associated with these chemicals to the
      environment and human health.

PMID- 24729387
TI  - Treatment of hypertrophic burn scars by combination laser-cision and pinhole
      method using a carbon dioxide laser.
AB  - BACKGROUND: Hypertrophic burn scars induce cosmetic and functional complications.
      Although there are various treatment modalities, an ideal method has not yet been
      found. Recently, numerous laser treatment modalities have been introduced with
      encouraging results. OBJECTIVE: To assess the efficacy and safety of combination
      therapy with laser-cision and pinhole method using a carbon dioxide (CO2 ) laser.
      METHODS: We conducted retrospective chart review of patients with hypertrophic
      burn scars treated by combination laser-cision and pinhole method from January
      2007 to December 2012. RESULTS: Nine patients with hypertrophic burn scars (mean
      age 31.2 years; range, 13-52 years) were treated with combination therapy over
      the past 6 years. Subjects were treated with one to three treatment sessions at 1
      year intervals by laser-cision and five to eight treatment sessions at 2- to 3
      month intervals by pinhole method. Two blinded observers evaluated photographs
      taken at baseline and 6 months after the final treatment. Compared with baseline,
      there was a mild to moderate improvement in all the patients (Grades 1-4; mean
      score: 2.89). The patient satisfaction survey revealed a mean improvement score
      of 3.11. CONCLUSION: Combination laser-cision and pinhole method using a CO2
      laser may be a new effective treatment option for patients with hypertrophic burn
      scars.

PMID- 24729388
TI  - The importance of systemic therapy in minimizing local recurrence after breast
      conserving surgery: the NSABP experience.
AB  - Adjuvant systemic therapy significantly reduces rates of distant recurrence and
      death. The effect of systemic therapy is not limited to reducing distant
      recurrences but also extends to reducing loco-regional recurrences, and rates of
      loco-regional recurrence have steadily declined over the past 25 years. This
      review focuses on the effect of adjuvant systemic therapy on rates of ipsilateral
      breast tumor recurrence following lumpectomy plus breast irradiation in several
      pivotal NSABP trials in early-stage breast cancer.

PMID- 24729389
TI  - Organizational climate and hospital nurses' caring practices: a mixed-methods
      study.
AB  - Organizational climate in healthcare settings influences patient outcomes, but
      its effect on nursing care delivery remains poorly understood. In this mixed
      methods study, nurse surveys (N = 292) were combined with a qualitative case
      study of 15 direct-care registered nurses (RNs), nursing personnel, and managers.
      Organizational climate explained 11% of the variation in RNs' reported frequency
      of caring practices. Qualitative data suggested that caring practices were
      affected by the interplay of organizational climate dimensions with patients and
      nurses characteristics. Workload intensity and role ambiguity led RNs to leave
      many caring practices to practical nurses and assistive personnel. Systemic
      interventions are needed to improve organizational climate and to support RNs'
      involvement in a full range of caring practices.

PMID- 24729391
TI  - Bright quantum-dot-sized single-chain conjugated polyelectrolyte nanoparticles:
      synthesis, characterization and application for specific extracellular labeling
      and imaging.
AB  - We report a simple method to fabricate quantum-dot-sized nanoparticles (NPs) from
      poly[9,9-bis((6-N,N,N-trimethylammonium)hexyl)fluorene-alt-co-2,1,3-benzo
      xadiazole dibromide] (PFBD). The transmission electron microscope results reveal
      that the obtained NPs have a mean diameter of ~4 nm, which is composed of a
      single PFBD chain. The NPs show bright fluorescence with an emission maximum at
      ~636 nm and a quantum yield of ~26% in water. The fluorescence properties of the
      NPs are characterized by steady fluorescence microscopy, fluorescence dynamic
      study and single nanoparticle microscopy, which show superior brightness over
      commercial quantum dots QD655. The NPs are further conjugated with streptavidin
      to yield PFBD-SA NPs, which serve as a specific extracellular labeling and
      imaging probe with high specificity and good photostability. 

PMID- 24729392
TI  - Survey on diversity of marine/saline anaerobic Heterolobosea (Excavata: Discoba)
      with description of seven new species.
AB  - Diversity of the anaerobic Heterolobosea (Excavata: Discoba) is only poorly
      understood, especially in marine environments. We have isolated and cultured 16
      strains of anaerobic heteroloboseid amoebae and flagellates from brackish, marine
      and saline anoxic habitats worldwide. Phylogenetic analyses of SSU rDNA sequences
      and light-microscopic observations showed that all the strains belong to the
      family Psalteriomonadidae, the main anaerobic lineage of Heterolobosea, and that
      they represent eight species from the genera Monopylocystis, Harpagon and
      Pseudoharpagon. Seven species are newly isolated and described here as
      Monopylocystis minor n. sp., Monopylocystis robusta n. sp., Monopylocystis
      elegans n. sp., Monopylocystis disparata n. sp., Harpagon salinus n. sp.,
      Pseudoharpagon longus n. sp. and Pseudoharpagon tertius n. sp. Amoebae, cysts and
      the ultrastructure of the genus Pseudoharpagon are presented for the first time. 

PMID- 24729390
TI  - Association of DNA base excision repair genes (OGG1, APE1 and XRCC1)
      polymorphisms with outcome to platinum-based chemotherapy in advanced nonsmall
      cell lung cancer patients.
AB  - Polymorphism of DNA base excision repair (BER) genes affects DNA repair capacity
      and may alter sensitivity to platinum-based chemotherapy regimens. This study
      investigated polymorphisms of OGG1 Ser326Cys, APE1 Asp148Glu APE1-141T/G and
      XRCC1 Arg399Gln for association with clinical outcome in 235 advanced inoperable
      nonsmall-cell lung cancer (NSCLC) patients after treatment with platinum-based
      chemotherapy. The multivariate analysis showed that OGG1 326 GC was associated
      with poor PFS [hazard ratio (HR) 1.730, p = 0.005], while XRCC1 399 GA, or GA+AA,
      was associated with poor OS in short-term period (HR 1.718, p = 0.003; HR 1.691,
      p = 0.003, respectively). Patients with OGG1 326/XRCC1 399 variant alleles had a
      higher risk to die early in short-term period (HR 1.929, p < 0.001). Furthermore,
      patients with XRCC1 399 variant allele (GA+AA) had higher risk of hematologic
      toxicity (p = 0.009), whereas patients carrying the OGG1 326 variant (GG), or the
      APE1-141 GG variant, had reduced risk of gastrointestinal toxicity (p = 0.015 and
      p = 0.023, respectively). The data from the current study provide evidence that
      OGG1 Ser326Cys, XRCC1 Arg399Gln, APE1 Asp148Glu, and APE1-141T/G polymorphisms
      may be useful in predicting clinical outcomes in patients with advanced
      inoperable NSCLC that will undergo platinum-based chemotherapy.

PMID- 24729393
TI  - Mucilaginibacter koreensis sp. nov., isolated from leaf mould.
AB  - A Gram-staining-negative, strictly aerobic, rod-shaped, pale-pink pigmented
      bacterial strain, designated TF8(T), was isolated from leaf mould in Cheonan,
      Republic of Korea. Its taxonomic position was determined through a polyphasic
      approach. Optimal growth occurred on R2A agar without NaCl supplementation, at 25
      28  degrees C and at pH 6.0-7.0. Phylogenetic analysis based on 16S rRNA gene
      sequences showed that strain TF8(T) belongs to the genus Mucilaginibacter in the
      family Sphingobacteriaceae. The sequence similarity between 16S rRNA genes of
      strain TF8(T) and the type strains of other species of the genus Mucilaginibacter
      ranged from 92.1 to 94.7%. The closest relatives of strain TF8(T) were
      Mucilaginibacter lutimaris BR-3(T) (94.7%), M. soli R9-65(T) (94.5%), M. litoreus
      BR-18(T) (94.5%), M. rigui WPCB133(T) (94.0%) and M. daejeonensis Jip 10(T)
      (93.8%). The major isoprenoid quinone was MK-7 and the major cellular fatty acids
      were iso-C15 : 0 (33.0%), summed feature 3 (C16 : 1omega7c and/or C16 : 1omega6c;
      24.8%) and summed feature 8 (C18 : 1omega7c and/or C18 : 1omega6c; 13.0%). The
      major polar lipids of TF8(T) were phosphatidylethanolamine and three unidentified
      aminophospholipids. The G+C content of the genomic DNA was 46.2 mol%. On the
      basis of the data presented here, strain TF8(T) is considered to represent a
      novel species of the genus Mucilaginibacter, for which the name Mucilaginibacter
      koreensis sp. nov. is proposed. The type strain is TF8(T) ( = KACC 17468(T) = JCM
      19323(T)).

PMID- 24729394
TI  - Microbacterium kyungheense sp. nov. and Microbacterium jejuense sp. nov.,
      isolated from salty soil.
AB  - Two novel strains, THG-C26(T) and THG-C31(T), were characterized using a
      polyphasic approach to determine their taxonomic positions. These two isolates
      were aerobic, Gram-stain-positive, non-motile, non-spore-forming and rod-shaped.
      16S rRNA gene sequences and phenotypic features including chemotaxonomic
      characteristics indicated that the two isolates clearly represented members of
      the genus Microbacterium. The quinone systems of strains THG-C26(T) and THG
      C31(T) contained MK-12/MK-13 as major menaquinones. The diamino acid in cell-wall
      hydrolysates of the two strains was ornithine. The major fatty acids were iso-C16
      : 0, anteiso-C15 : 0 and anteiso-C17 : 0. The polyamine pattern had spermidine as
      the predominant component. The major polar lipids were phosphatidylglycerol,
      diphosphatidylglycerol and unidentified glycolipids. Phenotypic characteristics
      supported the affiliation of strains THG-C26(T) and THG-C31(T) to the genus
      Microbacterium. Chemotaxonomic data and DNA-DNA relatedness values allowed
      differentiation of these strains from other species of the genus Microbacterium
      with validly published names. Strains THG-C26(T) and THG-C31(T) showed highest
      16S rRNA gene sequence similarities with Microbacterium resistens DMMZ 1710(T)
      (98.5%) and Microbacterium trichothecenolyticum IFO 15077(T) (98.8%),
      respectively, and the 16S rRNA gene sequence similarity between them was 99.0%.
      DNA-DNA hybridization values between the novel isolates and strains of other
      species of the genus Microbacterium with validly published names were 4-25%.
      Therefore, strains THG-C26(T) and THG-C31(T) are considered to represent two
      novel species of the genus Microbacterium, for which the names Microbacterium
      kyungheense sp. nov. [type strain THG-C26(T) ( = KACC 17124(T) = JCM 18735(T))]
      and Microbacterium jejuense sp. nov. [type strain THG-C31(T) ( = KACC 17123(T) =
      JCM 18734(T))] are proposed.

PMID- 24729396
TI  - Regulatory B cells are numerically but not functionally deficient in anti
      neutrophil cytoplasm antibody-associated vasculitis.
AB  - OBJECTIVES: B cells are central to the pathology of ANCA-associated vasculitis
      (AAV), a disease characterized by autoantibodies and effectively treated by
      rituximab. In addition to promoting inflammation, a subset of B cells act to
      suppress harmful autoimmune responses (Breg). The balance of effector and
      regulatory B cell subsets in AAV is not known. This study was conducted to assess
      the relative frequency of these subsets during different states of disease
      activity. METHODS: B memory (Bmem), naive (Bnaive) and regulatory (Breg) subsets
      were defined by their relative expression of CD24 and CD38. Function was assessed
      by cytokine production and suppressive action on CD4(+) Th1 activation evaluated
      in a co-culture system. RESULTS: Compared with healthy controls, the frequency of
      Breg (CD24(hi)CD38(hi)) was significantly reduced during disease remission in
      both proteinase 3 (PR3)- and MPO-ANCA patients and during acute disease in PR3
      ANCA patients, while the frequency of memory cells (CD24(hi)CD38(lo)) was reduced
      during active disease and restored during remission. Breg cell frequency showed a
      positive correlation, while Bmem had an inverse correlation with IL-10 production
      in vitro. B and T cell co-cultures revealed that memory and naive B cell subsets
      augmented Th1 activation in vitro, which was prevented by Breg, and this pattern
      did not differ between remission AAV patients and controls. CONCLUSION: In
      remission there is a numerical, but not functional, deficiency in Breg and
      preservation of Bmem associated with reduced IL-10 production and increased Th1
      activation in vitro. This imbalance may contribute to the high rate of relapse
      observed in AAV, especially in PR3-ANCA patients.

PMID- 24729397
TI  - Symptom complexes in patients with seropositive arthralgia and in patients newly
      diagnosed with rheumatoid arthritis: a qualitative exploration of symptom
      development.
AB  - OBJECTIVE: The aim of this study was to explore symptoms and symptom development
      during the earliest phases of RA in patients with seropositive arthralgia and
      patients newly diagnosed with RA. METHODS: Interviews were conducted with 15
      seropositive patients (anti-CCP positive, and often with arthralgia) and 11 newly
      presenting RA patients [classified according to the 2010 ACR/European League
      Against Rheumatism (EULAR) criteria]. Feedback procedures shared the experiences
      of seropositive arthralgia patients with early RA patients and vice versa. Data
      were analysed using thematic analysis. RESULTS: Symptoms common to both groups
      included joint pain, psychological distress, muscle cramps, abnormal skin
      sensations, stiffness, loss of motor control, weakness, fatigue and sleeping
      difficulties. Also, patterns of symptom evolution and the order of symptom
      development were described. Seropositive arthralgia patients described pain as
      annoying, while RA patients described how the severity of pain intensified before
      diagnosis, to the point where symptoms were psychologically distressing. Patients
      with seropositive arthralgia described reddening of the skin and burning
      sensations that they felt were indicative of the onset of swelling. Intense pain
      appeared to precede the onset of swelling for those with RA, which was often
      palindromic and travelled between joints until it later became persistent.
      CONCLUSION: This study highlights the breadth of symptoms that constitute the
      earliest phases of RA. Further research is needed to develop measures of symptom
      patterns and clusters to allow the predictive utility of symptoms to be assessed
      and to allow the integration of aspects of the patient's history into evidence
      based investigative and management algorithms for use in primary and secondary
      care.

PMID- 24729398
TI  - Safety and efficacy of golimumab in Chinese patients with active ankylosing
      spondylitis: 1-year results of a multicentre, randomized, double-blind, placebo
      controlled phase III trial.
AB  - OBJECTIVE: The aim of this study was to assess the efficacy and safety of
      golimumab in Chinese patients with active AS. METHODS: Two hundred and thirteen
      patients were randomized in a 1:1 ratio to receive either s.c. injections of
      placebo from weeks 0 to 20 followed by golimumab 50 mg from weeks 24 to 48 (group
      1, n = 105) or golimumab 50 mg from weeks 0 to 48 (group 2, n = 108), both every
      4 weeks. Placebo crossover occurred at week 24, while early escape was at week
      16. The primary endpoint was an improvement of at least 20% in the Assessment of
      SpondyloArthritis international Society (ASAS20) criteria at week 14. Major
      secondary endpoints included week 24 ASAS20 response and week 14 change scores
      for BASFI and BASMI. RESULTS: Golimumab treatment elicited significantly better
      responses than placebo in week 14 ASAS20 response [49.1% (53/108) vs 24.8%
      (26/105), respectively, P < 0.001], week 24 ASAS20 response (50.0% vs 22.9%, P <
      0.001) and mean improvements in BASFI (-1.26 vs 0.11, P < 0.001) and BASMI (-0.42
      vs -0.19, P = 0.021) scores at week 14. Additionally, golimumab treatment led to
      significant improvements in the mental and physical components of health-related
      quality of life (HRQoL) and sleep problems at week 24, all of which were further
      improved through week 52. During the 16-week placebo-controlled study period,
      31.4% and 30.6% of patients had adverse events (AEs) in groups 1 and 2,
      respectively; similar AE reporting rates were observed through week 24 (34.3% and
      32.0%) and among the golimumab-treated patients through week 56 (41.2%).
      CONCLUSION: Golimumab significantly reduced clinical symptoms/signs and improved
      physical function, range of motion and HRQoL in Chinese patients with active AS
      without unexpected safety concerns. TRIAL REGISTRATION: ClinicalTrials.gov,
      NCT01248793.

PMID- 24729399
TI  - BSR and BHPR guideline for the management of adults with ANCA-associated
      vasculitis.

PMID- 24729400
TI  - How should lupus flares be measured? Deconstruction of the safety of estrogen in
      lupus erythematosus national assessment-systemic lupus erythematosus disease
      activity index flare index.
AB  - OBJECTIVE: Accurate assessment of lupus flares is critical but problematic in
      clinical trials. This study examined the impact of modifications to the classic
      Safety of Estrogens in Lupus Erythematosus National Assessment (SELENA)-SLEDAI
      flare index (cSFI). METHODS: Ninety-one SLE patient records were evaluated at two
      visits at which the SLEDAI and BILAG had been scored prospectively. The cSFI was
      compared with an experimental version (eSFI) that eliminated medication criteria
      and separated the mild/moderate flare category into its components by clinical
      judgement based on records. The revised SFI (SFI-R) and some physician's global
      assessments (PGAs) were also scored using chart notes. RESULTS: eSFI-rated
      moderate flares had higher PGA and BILAG scores than those rated as mild. When
      medication criteria were excluded, 42 of 55 cSFI severe flares and 15 of 49
      mild/moderate flares were downgraded in severity. Comparing flares that remained
      severe with those that were downgraded, disease activity was higher by PGA (P <
      0.001), SLEDAI (P < 0.001), BILAG (P < 0.001), number of active BILAG organs (P <
      0.04) and flaring SFI-R organs (P < 0.01). PGA (P < 0.001) and the number of SFI
      R domains flaring (P < 0.001) were higher in mild/moderate eSFI flares than in
      those that were downgraded. Twenty-one of 83 (25%) medication changes occurred
      with no flare. Forty-six of 52 (88%) medication changes defining severe flare by
      cSFI involved patients rated by physicians with no, mild or moderate flares.
      CONCLUSION: A deconstructed flare index improves the discrimination of mild from
      moderate flares and selects more ill patients with true clinical worsening for
      each category of flare.

PMID- 24729401
TI  - First report of improvement of coeliac disease in a patient with Sjogren's
      syndrome treated with rituximab.

PMID- 24729402
TI  - Benefits and risks of low-dose glucocorticoid treatment in the patient with
      rheumatoid arthritis.
AB  - Glucocorticosteroids (GCs) have been employed extensively for the treatment of
      rheumatoid arthritis (RA) and other autoimmune and systemic inflammatory
      disorders. Their use is supported by extensive literature and their utility is
      reflected in their incorporation into current treatment guidelines for RA and
      other conditions. Nevertheless, there is still some concern regarding the long
      term use of GCs because of their potential for clinically important adverse
      events, particularly with an extended duration of treatment and the use of high
      doses. This article systematically reviews the efficacy for radiological and
      clinical outcomes for low-dose GCs (defined as <=10 mg/day prednisone equivalent)
      in the treatment of RA. Results reviewed indicated that low-dose GCs, usually
      administered in combination with synthetic DMARDs, most often MTX, significantly
      improve structural outcomes and decrease symptom severity in patients with RA.
      Safety data indicate that GC-associated adverse events are dose related, but
      still occur in patients receiving low doses of these agents. Concerns about side
      effects associated with GCs have prompted the development of new strategies aimed
      at improving safety without compromising efficacy. These include altering the
      structure of existing GCs and the development of delayed-release GC formulations
      so that drug delivery is timed to match greatest symptom severity. Optimal use of
      low-dose GCs has the potential to improve long-term outcomes for patients with
      RA. 

PMID- 24729403
TI  - Altered B cell balance, but unaffected B cell capacity to limit monocyte
      activation in anti-neutrophil cytoplasmic antibody-associated vasculitis in
      remission.
AB  - OBJECTIVE: Regulatory B cells (Bregs) constitute a subset of B cells with
      immunomodulatory properties. Numerical and functional alterations in the Breg
      compartment have been associated with autoimmunity. The aim of this study was to
      assess the frequency and function of Bregs in patients with ANCA-associated
      vasculitis (AAV). METHODS: B cell subsets were determined in the peripheral blood
      of 48 AAV patients (12 active, 36 in remission) and 41 healthy controls (HCs) by
      flow cytometry. Bregs were defined within the CD19(+) population as
      CD24(hi)CD38(hi) or CD24(hi)CD27(+) cells. The percentage of IL-10-positive B
      cells in circulation was analysed by flow cytometry. Sorted CD19(+) B cells were
      co-cultured with monocytes to evaluate their capacity to inhibit monocyte TNF
      alpha production upon lipopolysaccharide stimulation. RESULTS: The frequency of
      circulating CD19(+)CD24(hi)CD38(hi) cells was not different in AAV patients in
      remission compared with HCs, but was decreased in patients with active disease
      [mean in HCs 5.5% (s.d. 1.6) vs active 3.8% (s.d. 2.8), P = 0.0104]. Furthermore,
      the percentage of CD19(+)CD24(hi)CD27(+) cells was significantly decreased in
      both remission and active patients when compared with HCs [HCs 15.0% (s.d. 9.3)
      vs remission 6.6% (s.d. 4.4) (P < 0.0001) vs active 6.4% (s.d. 6.2) (P =
      0.0006)]. The frequency of IL-10-positive B cells was comparable between patients
      and HCs. B cells from AAV patients suppressed monocyte TNF-alpha production to a
      similar extent to cells from HCs. CONCLUSION: Based on immunophenotypic
      classification, Bregs are numerically diminished in AAV patients. However, B cell
      function in terms of IL-10 production and their capacity to suppress monocyte
      activation is not compromised in AAV patients in remission.

PMID- 24729405
TI  - Sn4+x P3 @ amorphous Sn-P composites as anodes for sodium-ion batteries with low
      cost, high capacity, long life, and superior rate capability.
AB  - Sn4+x P3 @ amorphous Sn-P composites are a promising cheap anode material for
      sodium-ion batteries with high capacity (502 mA h g(-1) at a current density of
      100 mA g(-1)), long cycling stability (92.6% capacity retention up to 100
      cycles), and high rate capability (165 mA h g(-1) at the 10C rate).

PMID- 24729404
TI  - Measurement confounding affects the extent to which verbal IQ explains social
      gradients in mortality.
AB  - BACKGROUND: IQ is thought to explain social gradients in mortality. IQ scores are
      based roughly equally on Verbal IQ (VIQ) and Performance IQ tests. VIQ tests,
      however, are suspected to confound true verbal ability with socioeconomic status
      (SES), raising the possibility that associations between SES and IQ scores might
      be overestimated. We examined, first, whether two of the most common types of VIQ
      tests exhibited differential item functioning (DIF) favouring persons of higher
      SES and/or majority race/ethnicity. Second, we assessed what impact, if any, this
      had on estimates of the extent to which VIQ explains social gradients in
      mortality. METHODS: Data from the General Social Survey-National Death Index
      cohort, a US population representative dataset, was used. Item response theory
      models queried social-factor DIF on the Thorndike Verbal Intelligence Scale and
      Wechsler Adult Intelligence Scales, Revised Similarities test. Cox models
      examined mortality associations among SES and VIQ scores corrected and
      uncorrected for DIF. RESULTS: When uncorrected for DIF, VIQ was correlated with
      income, education, occupational prestige and race, with correlation coefficients
      ranging between |0.12| and |0.43|. After correcting for DIF, correlations ranged
      from |0.06| to |0.16|. Uncorrected VIQ scores explained 11-40% of the Relative
      Index of Inequalities in mortality for social factors, while DIF-corrected scores
      explained 2-29%. CONCLUSIONS: Two of the common forms of VIQ tests appear
      confound verbal intelligence with SES. Since these tests appear in most IQ
      batteries, circumspection may be warranted in estimating the amount of social
      inequalities in mortality attributable to IQ.

PMID- 24729406
TI  - Improved transplant-free survival in patients with systemic sclerosis-associated
      pulmonary hypertension and interstitial lung disease.
AB  - OBJECTIVE: Survival in patients with systemic sclerosis (SSc)-associated
      pulmonary hypertension (PH) and interstitial lung disease (ILD) is poor. Evidence
      supporting the efficacy of aggressive pulmonary arterial hypertension (PAH)
      targeted therapy in this population is limited. The aim of this study was to
      investigate transplant-free survival in patients with isolated SSc-related PAH or
      SSc-related PH-ILD who were treated with aggressive PAH-targeted therapy.
      METHODS: SSc patients with right-sided heart catheterization (RHC)-diagnosed
      precapillary PH (mean pulmonary artery pressure >=25 mm Hg, pulmonary capillary
      wedge pressure <=15 mm Hg, and pulmonary vascular resistance >=240 dynes *
      second/cm(5) ) were included. Patients were classified as having ILD based on
      review of high-resolution computed tomography (CT) chest imaging and spirometry.
      The Kaplan-Meier method was applied and Cox proportional hazards models were
      constructed to analyze survival and identify predictive variables. RESULTS: Of 99
      patients with SSc-related precapillary PH, 28% had SSc-related PAH and 72% had
      SSc-related PH-ILD. The 1- and 2-year survival estimates were, respectively, 72%
      and 59% in the SSc-related PH-ILD group versus 82% and 66% in the SSc-related PAH
      group (P = 0.5). Within 6 months of the diagnostic RHC, 24% of all patients were
      started on prostanoid therapy; an additional 24% were started on prostanoid
      therapy after 6 months. In the multivariate model, male sex (hazard ratio [HR]
      0.7, P = 0.01) and prostanoid therapy initiation within 6 months of the RHC (HR
      1.4, P = 0.01) were the only factors significantly associated with transplant
      free survival, after accounting for the presence of ILD and severity of PH.
      CONCLUSION: In this study, survival of patients with SSc-related PH-ILD was
      modestly improved relative to historical series. While these findings may not be
      generalizable, improved survival may be due partly to aggressive PAH-targeted
      therapy.

PMID- 24729407
TI  - Post-marketing surveillance of the safety profile of iodixanol in the outpatient
      CT setting: a prospective, multicenter, observational study of patient risk
      factors, adverse reactions and preventive measures in 9953 patients.
AB  - PURPOSE: Non-interventional study in outpatient, contrast-enhanced CT; 1. to
      determine the extent of preventive measures for risk reduction of adverse drug
      reactions after contrast-enhanced CT examinations. 2. to prospectively determine
      the incidence and severity of adverse drug reactions occurring after
      administration of the iso-osmolar contrast medium iodixanol. 3. to determine a
      possible influence of preventive measures on the incidence/severity of adverse
      drug reactions.. MATERIALS AND METHODS: Evaluable documentation was provided for
      9953 patients from 66 radiology centers across Germany. Patient characteristics,
      aspects of iodixanol administration, and adverse events with an at least
      "possible" relationship were documented on a standardized case report form (CRF)
      and were evaluated up to seven days after contrast medium administration.
      RESULTS: About 55.5 % of patients showed one or more risk factors (e. g. impaired
      renal function 4.4 %, diabetes mellitus 8.5 %, hypertension 20.6 %). One third of
      the sites did not implement any preventive measures. Patients with a known risk
      for an allergy-like reaction were more likely to receive pharmacologic preventive
      treatment (0.5 - 50.5 %). Oral hydration was the main preventive measure in
      patients with renal risk factors (< 8 %) followed by intravenous hydration (1 %).
      Adverse drug reactions, mainly hypersensitivity reactions, occurred in 77
      patients (0.74 %), but were classified as serious in only 3 patients (0.03 %). No
      statistically significant correlation between risk factors, preventive measures,
      and adverse reactions could be found. CONCLUSION: The use of preventive measures
      for CT examinations in this outpatient setting was generally low with risk
      patients being pre-medicated more often, depending on their history. In the
      routine outpatient setting, iso-osmolar iodixanol was very well tolerated in
      almost 10,000 patients undergoing diagnostic CT. The rate of acute and delayed
      adverse reactions was low. No correlation could be found between risk factors,
      preventive measures and the incidence of adverse drug reactions. KEY POINTS: *
      Rare use of preventive measures for outpatient CT examinations.* Low rate of
      acute and late adverse drug reactions to iodixanol.* No correlation between risk
      factors, preventive measures and adverse drug reactions.

PMID- 24729408
TI  - Split-bolus single-phase cardiac multidetector computed tomography for reliable
      detection of left atrial thrombus: comparison to transesophageal
      echocardiography.
AB  - PURPOSE: Evaluation of a new cardiac MDCT protocol using a split-bolus contrast
      injection protocol and single MDCT scan for reliable diagnosis of LA/LAA thrombi
      in comparison to TEE, optimizing radiation exposure and use of contrast agent.
      MATERIALS AND METHODS: A total of 182 consecutive patients with drug refractory
      AF scheduled for PVI (62.6 % male, mean age: 64.1 +/- 10.2 years) underwent
      routine diagnostic work including TEE and cardiac MDCT for the evaluation of
      LA/LAA anatomy and thrombus formation between November 2010 and March 2012.
      Contrast media injection was split into a pre-bolus of 30 ml and main bolus of 70
      ml iodinated contrast agent separated by a short time delay. RESULTS: In this
      study, split-bolus cardiac MDCT identified 14 of 182 patients with filling
      defects of the LA/LAA. In all of these 14 patients, abnormalities were found in
      TEE. All 5 of the 14 patients with thrombus formation in cardiac MDCT were
      confirmed by TEE. CONCLUSION: MDCT was 100 % accurate for thrombus, with strong
      but not perfect overall results for SEC equivalent on MDCT. KEY POINTS: *
      Patients with no filling defect or thrombus in MDCT in the LA/LAA region are
      unlikely to have thrombus and may undergo PVI without TEE.* Here, the role of an
      additional TEE in pre-procedural management prior to PVI in patients with AF has
      to be redefined.* Using a split-bolus injection protocol increases the diagnostic
      accuracy of thrombus in the LA/LAA region.

PMID- 24729409
TI  - Chemosaturation with percutaneous hepatic perfusions of melphalan for hepatic
      metastases: experience from two European centers.
AB  - PURPOSE: Chemosaturation with percutaneous hepatic perfusion (PHP; Hepatic
      CHEMOSAT((r)) Delivery System; Delcath Systems Inc, USA) is a minimally invasive,
      repeatable regional therapy for unresectable hepatic metastases. It uses a system
      of catheters and filters to isolate hepatic venous blood from the systemic
      circulation, allowing delivery of high-dose chemotherapy to the hepatic artery.
      Effluent hepatic venous blood is filtered before being returned to the systemic
      circulation, thereby reducing exposure to chemotherapy. We describe our
      experiences with chemosaturation-PHP at 2 European centers. MATERIALS AND
      METHODS: 14 patients presented unresectable hepatic metastases from solid tumors;
      13 received 1 - 3 sessions of chemosaturation-PHP. Melphalan 2.0 (n = 1) or 3.0
      (n = 12) mg/kg was given as a 30-minute infusion into the hepatic artery. 12
      patients were evaluable for tumor response. RESULTS: One complete
      (cholangiocarcinoma, n = 1) and 6 partial responses (ocular, n = 3 or cutaneous
      melanoma, n = 3) were observed, 5 patients had stable disease (ocular melanoma, n
      = 3; breast cancer, n = 1; gastric cancer, n = 1). Mild to moderate filter
      related toxicity (i. e. thrombocytopenia, anemia) was observed immediately post
      procedure. Grade 3/4 melphalan-related pancytopenia developed after 1 - 2 weeks.
      All hematological events were managed effectively with transfusions and/or other
      supportive measures. The new high-efficiency filter showed milder toxicity and
      faster recovery. In one case, chemosaturation-PHP was abandoned prematurely due
      to heparin-induced vaginal bleeding, and one patient died due to retroperitoneal
      hemorrhage from heparin anti-coagulation. CONCLUSION: Chemosaturation-PHP for non
      resectable liver metastases is a feasible treatment option when performed by an
      experienced multi-disciplinary team. It may be a promising regional therapy for
      patients with no effective treatment options.

PMID- 24729410
TI  - Gene silencing of two acetylcholinesterases reveals their cholinergic and non
      cholinergic functions in Rhopalosiphum padi and Sitobion avenae.
AB  - BACKGROUD: The function of acetylcholinesterase (AChE) is to terminate synaptic
      transmission by hydrolysing the neurotransmitter acetylcholine (ACh) in the
      synaptic cleft, and thus it is an effective target for organophosphate (OP) and
      carbamate (CB) insecticides. RESULTS: The transcript levels of the four Ace genes
      were dramatically suppressed by injection of their respective dsRNA in
      Rhopalosiphum padi and Sitobion avenae. However, the AChE activity changes in the
      Ace1 knockdown aphids were consistent with the significant transcript level
      changes of Ace1 genes in these aphids, but not for Ace2. Bioassay results
      indicated that the suppression of RpAce1 increased its susceptibilities to
      pirimicarb and malathion, and SaAce1 silencing also increased susceptibility to
      pirimicarb in S. avenae, whereas the knockdowns of RpAce2 and SaAce2 had a slight
      effect on their susceptibilities. The knockdown of Ace1 genes also caused
      significant reductions in fecundity in the aphids of their parental generation.
      CONCLUSIONS: These results suggest that AChE1 is a predominant cholinergic enzyme
      and is the target of anticholinesterase insecticides in both R. padi and S.
      avenae. It also plays a non-cholinergic role in fecundity of these aphids. AChE2
      may also be important for the toxicological function, although its importance
      appeared to be lower than that of AChE1.

PMID- 24729411
TI  - Twelve-month prevalence, comorbidity and correlates of mental disorders in
      Germany: the Mental Health Module of the German Health Interview and Examination
      Survey for Adults (DEGS1-MH).
AB  - This paper provides up to date prevalence estimates of mental disorders in
      Germany derived from a national survey (German Health Interview and Examination
      Survey for Adults, Mental Health Module [DEGS1-MH]). A nationally representative
      sample (N = 5318) of the adult (18-79) population was examined by clinically
      trained interviewers with a modified version of the Composite International
      Diagnostic Interview (DEGS-CIDI) to assess symptoms, syndromes and diagnoses
      according to DSM-IV-TR (25 diagnoses covered). Of the participants 27.7% met
      criteria for at least one mental disorder during the past 12 months, among them
      44% with more than one disorder and 22% with three or more diagnoses. Most
      frequent were anxiety (15.3%), mood (9.3%) and substance use disorders (5.7%).
      Overall rates for mental disorders were substantially higher in women (33% versus
      22% in men), younger age group (18-34: 37% versus 20% in age group 65-79), when
      living without a partner (37% versus 26% with partnership) or with low (38%)
      versus high socio-economic status (22%). High degree of urbanization (> 500,000
      inhabitants versus < 20,000) was associated with elevated rates of psychotic
      (5.2% versus 2.5%) and mood disorders (13.9% versus 7.8%). The findings confirm
      that almost one third of the general population is affected by mental disorders
      and inform about subsets in the population who are particularly affected.

PMID- 24729413
TI  - Iatrogenic lymphoproliferative disorder.

PMID- 24729412
TI  - Assessment of early occlusal caries pre- and post-sealant application--an imaging
      approach.
AB  - BACKGROUND AND OBJECTIVE: Clinicians have difficulty assessing and monitoring
      early occlusal caries. Traditional clinical exam and radiographs are unable to
      detect the subtle alterations in enamel indicative of de- or re-mineralization,
      particularly under dental sealants. Although clinicians have used laser
      fluorescence (LF) to address this gap, this modality has demonstrated weak
      correlation with histology. The International Caries Detection and Assessment
      System (ICDAS-II) has demonstrated high sensitivity and specificity for caries
      detection, but since it is based on visual assessment, it is of no use in areas
      beneath the most commonly used dental sealants which are opaque. Optical
      coherence tomography (OCT) is an emergent assessment tool which has demonstrated
      great promise in detecting and quantifying caries, including areas beneath
      commonly used dental sealants and composites. However, OCT has not yet been
      widely integrated into clinical dental practice, perhaps because OCT imaging does
      not provide an easily accessible diagnostic outcome for clinicians. The objective
      of this ex vivo study was to use OCT-images of sound and carious occlusal
      surfaces in combination with a simple algorithm to compare the caries detection
      ability of OCT with tools clinicians may be more familiar with (LF and
      radiography), and with an established valid and reliable clinical assessment tool
      (ICDAS-II). STUDY DESIGN/MATERIALS AND METHODS: One hundred twenty extracted
      teeth with sound or naturally carious occlusal surfaces were imaged with OCT, LF,
      radiography, and examined clinically with the ICDAS-II. Teeth were randomized to
      one of two dental sealants recommended for use with LF. A novel simple algorithm
      was used to interpret OCT-based images. The accuracy of caries severity
      assessments of the OCT-based diagnosis, LF, ICDAS-II, and digital radiography
      were compared to the 4-point histological analysis gold standard. RESULTS: OCT
      and ICDAS-II caries severity assessments demonstrated high sensitivity (94.0%;
      92.3%) and specificity (85.0%; 83.3%), LF demonstrated low sensitivity (65.2%)
      but high specificity (97.6%), and digital radiography demonstrated low
      sensitivity (67.1%) with moderate specificity (79.5%) on unsealed occlusal
      surfaces. OCT-based caries severity assessments of sealed teeth demonstrated high
      specificity (97.6%), sensitivity (89.9%), excellent positive predictive value
      (98.6%), and negative predictive value (83.3%). Despite our use of LF recommended
      dental sealants, in the presence of sealants, LF assessment of caries severity
      demonstrated high sensitivity (95.1%), but extremely low specificity (10.3%),
      positive predictive value (68.8%), and negative predictive value (50.0%).
      CONCLUSION: This study found that OCT-based imaging combined with a simple
      diagnostic algorithm accurately assessed the severity of natural early caries on
      occlusal surfaces in extracted teeth both in the absence and presence of dental
      sealant. The findings of this study support the clinical use of OCT imaging for
      assessment and monitoring progression of early non-cavitated caries lesions on
      occlusal surfaces including areas under dental sealants.

PMID- 24729414
TI  - Encapsulated Fe3O4 /Ag complexed cores in hollow gold nanoshells for enhanced
      theranostic magnetic resonance imaging and photothermal therapy.
AB  - Designed and fabrication of a novel magnetic hollow gold nanoshell complexes that
      incorporates iron oxide nanoparticles in the hollow interior. The combined effect
      of the smaller IONPs improved the overall magnetic properties of the design and
      MRI contrast capability. The overall complex could be synthesized in the range of
      60-80 nm in diameter while still having a plasmonic peak in the near infrared
      region. 

PMID- 24729415
TI  - Immunotherapy of B-cell non-Hodgkin lymphoma by targeting the chemokine receptor
      CXCR5 in a preclinical mouse model.
AB  - Bispecific antibodies are promising agents for immunotherapy. Here, we describe a
      quadroma-based trifunctional bispecific antibody binding the chemokine receptor
      CXCR5 and the T-cell antigen CD3 that efficiently prevents tumor growth in a
      mouse B-cell lymphoma model. CXCR5 regulates the tissue homeostasis of mature B
      cells and is highly expressed on B-cell non-Hodgkin and lymphocyte-predominant
      Hodgkin lymphoma, as well as on a subset of CD4(+) T cells known as follicular T
      helper cells. In vitro, the bispecific CXCR5::CD3 antibody efficiently recruited
      effector T cells to CXCR5 expressing B cells and induced a co-stimulation
      independent activation of CD8(+) and CD4(+) T cells as demonstrated by the de
      novo expression of CD25 and CD69, and secretion of the cytokines IFN-gamma, TNF
      alpha, IL-6 and IL-10 by peripheral blood mononuclear cells. Notably, at low
      antibody concentrations, CXCR5::CD3 displayed a significantly higher cytotoxic
      activity against autologous B cells than its parental antibodies or rituximab. In
      vivo imaging revealed that CXCR5::CD3 and its parental CXCR5 antibody efficiently
      prevent tumor growth in a xenograft model of B-cell lymphoma in mice and prolong
      their survival. Taken together, our results identify CXCR5 as a promising target
      for antibody-based therapies in the treatment of B-cell malignancies.

PMID- 24729416
TI  - Low concentration structural dynamics of lanreotide and somatostatin-14.
AB  - Lanreotide, a synthetic cyclic octapeptide, analogue of the peptide hormone
      somatostatin-14 (SST-14), is routinely used as a long-acting medication in the
      management of neuroendocrine tumors. Despite its therapeutic importance, low
      concentration structural data is still lacking for lanreotide. In fact, the major
      part of the previous structural investigations were focused on the remarkable
      aggregation properties of this peptide, appearing at high concentrations (>5 mM).
      Here, we have applied three optical spectroscopic techniques, i.e. fluorescence,
      circular dichroism and Raman scattering, for analyzing the structural dynamics at
      the concentrations below 5 mM, where lanreotide exists either in a monomer state
      or at the first stages of aggregation. The obtained data from lanreotide were
      discussed through their comparison with those collected from SST-14, leading us
      to the following conclusions: (i) The central D-Trp residue, forming with its
      adjacent Lys the main receptor interacting part of lanreotide, keeps a constant
      high rotational freedom whatever the environment (water, water/methanol,
      methanol). (ii) A solvent-dependent tight beta-turn, belonging to the type-II'
      family, is revealed in lanreotide. (iii) Raman data analyzed by band
      decomposition in the amide (I and III) regions allowed estimation of different
      secondary structural elements within the millimolar range. Interestingly, the
      applied protocol shows a perfect agreement between the structural features
      provided by the amide I and amide III Raman markers.

PMID- 24729417
TI  - Proteomic analysis of hypoxia-induced U373MG glioma secretome reveals novel
      hypoxia-dependent migration factors.
AB  - High-grade gliomas are one of the most common brain tumors and notorious for poor
      prognosis due to their malignant nature. Gliomas have an extensive area of
      hypoxia, which is critical for glioma progression by inducing aggressiveness and
      activating the angiogenesis process in the tumor microenvironment. To resolve the
      factors responsible for the highly malignant nature of gliomas, we
      comprehensively profiled the U373MG glioma cell secretome-exosome and soluble
      fraction under hypoxic and normoxic conditions. A total of 239 proteins were
      identified from the exosome and soluble fractions. Vascular endothelial growth
      factor, stanniocalcin 1 (STC1) and stanniocalcin 2, and insulin-like growth
      factor binding protein 3 and 6, enriched in the soluble fraction, and lysyl
      oxidase homolog 2 enriched in the exosomal fraction were identified as
      upregulated proteins by hypoxia based on a label-free quantitative analysis. STCs
      and insulin-like growth factor binding proteins, which were identified as
      secretory proteins under hypoxic conditions, were highly correlated with glioma
      grade in human patients by microarray analysis. An in vitro scratch wound assay
      revealed that STC1 and 2 have important functions in the induction of cell
      migration in a hypoxia-dependent manner, suggesting that they are hypoxia
      dependent migration factors. 

PMID- 24729420
TI  - Flow-through synthesis on Teflon-patterned paper to produce peptide arrays for
      cell-based assays.
AB  - A simple method is described for the patterned deposition of Teflon on paper to
      create an integrated platform for parallel organic synthesis and cell-based
      assays. Solvent-repelling barriers made of Teflon-impregnated paper confine
      organic solvents to specific zones of the patterned array and allow for 96
      parallel flow-through syntheses on paper. The confinement and flow-through mixing
      significantly improves the peptide yield and simplifies the automation of this
      synthesis. The synthesis of 100 peptides ranging from 7 to 14 amino acids in
      length gave over 60% purity for the majority of the peptides (>95% yield per
      coupling/deprotection cycle). The resulting peptide arrays were used in cell
      based screening to identify 14 potent bioactive peptides that support the
      adhesion or proliferation of breast cancer cells in a 3D environment. In the
      future, this technology could be used for the screening of more complex
      phenotypic responses, such as cell migration or differentiation.

PMID- 24729421
TI  - Preparation of three-dimensional macroporous chitosan-gelatin B microspheres and
      HepG2-cell culture.
AB  - Chitosan-gelatin B microspheres with an open, interconnected, highly macroporous
      (100-200 um) structure were prepared via a three-step protocol combining freeze
      drying with an electrostatic and ionic cross-linking method. Saturated
      tripolyphosphate ethanol solution (85% ethanol) was chosen as the crosslinking
      agent to prevent destruction of the porous structure and to improve the
      biostability of the chitosan-gelatin B microspheres, with N-(3
      dimethylaminopropyl)-N'-ethyl-carbodiimide/N-hydroxysuccinimide as a second
      crosslinking agent to react with gelatin A and fixed chitosan-gelatin B
      microspheres to attain improved biocompatibility. Water absorption of the three
      dimensional macroporous chitosan-gelatin B microspheres (3D-P-CGMs) was 12.84,
      with a porosity of 85.45%. In vitro lysozyme degradation after 1, 3, 5, 7, 10,
      14, and 21 days showed improved biodegradation in the 3D-P-CGMs. The morphology
      of human hepatoma cell lines (HepG2 cells) cultured on the 3D-P-CGMs was
      spherical, unlike that of cells cultured under traditional two-dimensional
      conditions. Scanning electron microscopy and paraffin sections were used to
      confirm the porous structure of the 3D-P-CGMs. HepG2 cells were able to migrate
      inside through the pore. Cell proliferation and levels of albumin and lactate
      dehydrogenase suggested that the 3D-P-CGMs could provide a larger specific
      surface area and an appropriate microenvironment for cell growth and survival.
      Hence, the 3D-P-CGMs are eminently suitable as macroporous scaffolds for cell
      cultures in tissue engineering and cell carrier studies. Copyright (c) 2014 John
      Wiley & Sons, Ltd.

PMID- 24729422
TI  - Virtual-reality simulation-based training in ultrasound.

PMID- 24729423
TI  - Medicine and the holistic understanding of the human being: ultrasound
      examination as dialog.
AB  - Ultrasound can capture the living nature of a person. This capturing of life
      depends greatly on experience as well as sense of touch, intuition, sense of
      speech, and not least a sense for the distinctiveness of every person. Performing
      ultrasound is not simply the application of a technique but rather a merging of
      man and technology in the framework of an interpersonal encounter. Therefore, as
      much should be invested in the interpersonal nature of the encounter as in the
      development of the technical principles of the ultrasound probe. To effectively
      perform ultrasound, it is necessary to avoid viewing ultrasound from a purely
      technical view and to always remember the importance of the relationship to the
      patient, particularly during the technical examination.

PMID- 24729424
TI  - Dietary pattern trajectories during 15 years of follow-up and HbA1c, insulin
      resistance and diabetes prevalence among Chinese adults.
AB  - BACKGROUND: Most research on dietary patterns and health outcomes does not
      include longitudinal exposure data. We used an innovative technique to capture
      dietary pattern trajectories and their association with haemoglobin A1c (HbA1c),
      homeostasis model of insulin resistance (HOMA-IR) and prevalence of newly
      diagnosed diabetes. METHODS: We included 4096 adults with 3-6 waves of diet data
      (1991-2006) and biomarkers measured in 2009 from the China Health and Nutrition
      Survey. Diet was assessed with three 24-h recalls and a household food inventory.
      We used a dietary pattern previously identified with reduced rank regression that
      positively predicted diabetes in 2006 (high in wheat products and soy milk and
      low in rice, legumes, poultry, eggs and fish). We estimated a score for this
      dietary pattern for each subject at each wave. Using latent class trajectory
      analysis, we grouped subjects with similar dietary pattern score trajectories
      over time into five classes. RESULTS: Three trajectory classes were stable over
      time, and in two classes the diet became unhealthier over time (upward trend in
      dietary pattern score). Among two classes with similar scores in 2006, the one
      with the lower (healthier) initial score had an HbA1c 1.64% lower (-1.64 (95% CI 
      3.17 to -0.11)) and non-significantly a HOMA-IR 6.47% lower (-6.47 (-17.37 to
      4.42)) and lower odds of diabetes (0.86 (0.44 to 1.67)). CONCLUSIONS: Our
      findings suggest that dietary pattern trajectories with healthier scores
      longitudinally had a lower HbA1c compared with those with unhealthier scores,
      even when the trajectories had similar scores in the end point.

PMID- 24729425
TI  - Cohort Profile: The Malaysian Cohort (TMC) project: a prospective study of non
      communicable diseases in a multi-ethnic population.
AB  - The Malaysian Cohort study was initiated in 2005 by the Malaysian government. The
      top-down approach to this population-based cohort study ensured the allocation of
      sufficient funding for the project which aimed to recruit 100,000 individuals
      aged 35-70 years. Participants were recruited from rural and urban areas as well
      as from various socioeconomic groups. The main objectives of the study were to
      identify risk factors, to study gene-environment interaction and to discover
      biomarkers for the early detection of cancers and other diseases. At recruitment,
      a questionnaire-based interview was conducted, biophysical measurements were
      performed and biospecimens were collected, processed and stored. Baseline
      investigations included fasting blood sugar, fasting lipid profile, renal profile
      and full blood count. From April 2006 to the end of September 2012 we recruited a
      total of 106,527 participants. The baseline prevalence data showed 16.6%
      participants with diabetes, 46.5% with hypertension, 44.9% with
      hypercholesterolaemia and 17.7% with obesity. The follow-up phase commenced in
      June 2013. This is the most comprehensive and biggest cohort study in Malaysia,
      and has become a valuable resource for epidemiological and biological research.
      For information on collaboration and also data access, investigators can contact
      the project leader at (rahmanj@ppukm.ukm.edu.my).

PMID- 24729426
TI  - Cohort profile update: The 1993 Pelotas (Brazil) birth cohort follow-up visits in
      adolescence.
AB  - In this paper we update the profile of the 1993 Pelotas (Brazil) Birth Cohort
      Study, with emphasis on a shift of priority from maternal and child health
      research topics to four main categories of outcome variables, collected
      throughout adolescence: (i) mental health; (ii) body composition; (iii) risk
      factors for non-communicable diseases (NCDs); (iv) human capital. We were able to
      trace 81.3% (n = 4106) of the original cohort at 18 years of age. For the first
      time, the 18-years visit took place entirely on the university premises, in a
      clinic equipped with state-of-the-art equipment for the assessment of body
      composition. We welcome requests for data analyses from outside scientists. For
      more information, refer to our website (http://www.epidemio
      ufpel.org.projetos_de_pesquisas/estudos/coorte_1993) or e-mail the corresponding
      author. 

PMID- 24729427
TI  - Alcohol consumption and risk of incident rheumatoid arthritis in women: a
      prospective study.
AB  - OBJECTIVE: To evaluate the association of alcohol consumption with the risk of
      rheumatoid arthritis (RA) in 2 large prospective cohorts, the Nurses' Health
      Study (NHS) and NHSII. METHODS: The NHS was established in 1976 and enrolled
      121,701 female registered nurses in the US. The NHSII began in 1989, enrolling
      116,430 female nurses. Lifestyle and environmental exposures were collected
      through biennial questionnaires. Alcohol consumption was assessed with a food
      frequency questionnaire, which was completed every 4 years. Incident RA cases
      were identified using a connective tissue disease screening questionnaire and a
      medical record review. Separate Cox proportional hazards models were used to
      estimate hazard ratios (HRs) after adjusting for potential confounders in the NHS
      and NHSII. The pooled HR from 2 cohorts was estimated using a DerSimonian and
      Laird random-effects model. RESULTS: Among 1.90 million person-years from 1980 to
      2008, 580 incident cases of RA were diagnosed in the NHS cohort, and among 1.78
      million person-years from 1989 to 2009, 323 incident cases of RA were diagnosed
      in the NHSII cohort. Compared to no use, the pooled multivariable adjusted HR for
      alcohol use of 5.0-9.9 gm/day was 0.78 (95% confidence interval [95% CI] 0.61
      1.00). For seropositive RA cases, the association appeared stronger (HR 0.69 [95%
      CI 0.50-0.95]). In addition, women who drank beer 2-4 times a week had a 31%
      decreased risk compared to women who never drank beer. CONCLUSION: We found a
      modest association between long-term moderate alcohol drinking and reduced risk
      of RA. Future studies are needed to confirm our findings in other populations.

PMID- 24729428
TI  - The value of high-dose chemotherapy in patients with first relapsed Ewing
      sarcoma.
AB  - BACKGROUND: Prognosis of patients with relapsed Ewing sarcoma (ES) is poor. The 5
      year overall survival (OS) is 13%. We analyzed high-dose chemotherapy (HDtx)
      versus conventional chemotherapy (CHtx) in patients with relapsed ES. PROCEDURE:
      Data from 239 patients with first relapse, registered during 2000-2011 in the ES
      relapse registry of the Cooperative Ewing Sarcoma Study Group (CESS) were
      analyzed. RESULTS: Of 239 patients, 200 received various non-HDtx second-line
      CHtx regimens. Seventy-three patients had additional HDtx followed by autologous
      stem cell rescue. The 2-year event-free survival (EFS) was 10% (SE = 0.02) in
      patients treated without HDtx and 45% (SE = 0.09) in patients treated with HDtx.
      In a second step, we focused on those patients who achieved complete remission
      (CR) or partial remission (PR) after four to six cycles of conventional second
      line CHtx. Here, the 2-year EFS was 31% (SE = 0.08) without additional HDtx and
      44% (SE = 0.09) with additional HDtx. In addition, multivariate regression
      analysis indicates absence of HDtx treatment, with a Hazard ratio (HR) of 2.90
      (95% CI 1.41-6.0), and early relapse, with a HR of 4.76 (95% CI 2.31-9.78), as
      independent prognostic factors for EFS. CONCLUSION: Additional HDtx may
      contribute to further reduce the risk of further events in patients who respond
      to conventional second-line CHtx.

PMID- 24729430
TI  - Magnetic resonance support vector machine discriminates essential tremor with
      rest tremor from tremor-dominant Parkinson disease.
AB  - BACKGROUND: The aim of the current study was to distinguish patients who had
      tremor-dominant Parkinson's disease (tPD) from those who had essential tremor
      with rest tremor (rET). METHODS: We combined voxel-based morphometry-derived gray
      matter and white matter volumes and diffusion tensor imaging-derived mean
      diffusivity and fractional anisotropy in a support vector machine (SVM) to
      evaluate 15 patients with rET and 15 patients with tPD. Dopamine transporter
      single-photon emission computed tomography imaging was used as ground truth.
      RESULTS: SVM classification of individual patients showed that no single
      predictor was able to fully discriminate patients with tPD from those with rET.
      By contrast, when all predictors were combined in a multi-modal algorithm, SVM
      distinguished patients with rET from those with tPD with an accuracy of 100%.
      CONCLUSIONS: SVM is an operator-independent and automatic technique that may help
      distinguish patients with tPD from those with rET at the individual level.

PMID- 24729431
TI  - In vitro ketamine CYP3A-mediated metabolism study using mammalian liver S9
      fractions, cDNA expressed enzymes and liquid chromatography tandem mass
      spectrometry.
AB  - Ketamine is widely used in medicine in combination with several benzodiazepines,
      including midazolam. The objectives of this study were to develop a novel HPLC
      MS/selected reaction monitoring (SRM) method capable of quantifying ketamine and
      norketamine using an isotopic dilution strategy in biological matrices and study
      the formation of norketamine, the principal metabolite of ketamine with and
      without the presence of midazolam, a well-known CYP3A substrate. The
      chromatographic separation was achieved using a Thermo Betasil Phenyl 100 * 2 mm
      column combined with an isocratic mobile phase composed of acetonitrile,
      methanol, water and formic acid (60:20:20:0.4) at a flow rate of 300 MUL/min. The
      mass spectrometer was operating in selected reaction monitoring mode and the
      analytical range was set at 0.05-50 MUm. The precision (CV) and accuracy (NOM)
      observed were 3.9-7.8 and 95.9-111.1% respectively. The initial rate of formation
      of norketamine was determined using various ketamine concentrations and Km values
      of 18.4, 13.8 and 30.8 MUm for rat, dog and human liver S9 fractions were
      observed, respectively. The metabolic stability of ketamine on liver S9 fractions
      was significantly higher in human (T1/2  = 159.4 min) compared with rat (T1/2  =
      12.6 min) and dog (T1/2  = 7.3 min) liver S9 fractions. Moreover significantly
      lower IC50 and Ki values observed in human compared with rat and dog liver S9
      fractions. Experiments with cDNA expressed CYP3A enzymes showed that the
      formation of norketamine is mediated by CYP3A but results suggest an important
      contribution from other isoenzymes, most likely CYP2C particularly in rat.

PMID- 24729432
TI  - Facile method for the site-specific, covalent attachment of full-length IgG onto
      nanoparticles.
AB  - Antibodies, most commonly IgGs, have been widely used as targeting ligands in
      research and therapeutic applications due to their wide array of targets, high
      specificity and proven efficacy. Many of these applications require antibodies to
      be conjugated onto surfaces (e.g. nanoparticles and microplates); however, most
      conventional bioconjugation techniques exhibit low crosslinking efficiencies,
      reduced functionality due to non-site-specific labeling and random surface
      orientation, and/or require protein engineering (e.g. cysteine handles), which
      can be technically challenging. To overcome these limitations, we have
      recombinantly expressed Protein Z, which binds the Fc region of IgG, with an UV
      active non-natural amino acid benzoylphenyalanine (BPA) within its binding
      domain. Upon exposure to long wavelength UV light, the BPA is activated and forms
      a covalent link between the Protein Z and the bound Fc region of IgG. This
      technology was combined with expressed protein ligation (EPL), which allowed for
      the introduction of a fluorophore and click chemistry-compatible azide group onto
      the C-terminus of Protein Z during the recombinant protein purification step.
      This enabled the crosslinked-Protein Z-IgG complexes to be efficiently and site
      specifically attached to aza-dibenzocyclooctyne-modified nanoparticles, via
      copper-free click chemistry. 

PMID- 24729434
TI  - Detection of methemoglobin in whole blood based on confocal micro-Raman
      spectroscopy and multivariate statistical techniques.
AB  - Raman spectroscopy has been shown to have the potential for revealing oxygenated
      and spin ability of hemoglobin. In this study, confocal micro-Raman spectroscopy
      is developed to monitor the effect of sodium nitrite on oxyhemoglobin (HbO2 ) in
      whole blood. We observe that the band at 1,638 cm(-1) which is sensitive to the
      oxidation state decreases dramatically, while the 1,586 cm(-1) (low-spin state
      band) reduces both in methemoglobin (MetHb) and poisoning blood. Our results show
      that adding in sodium nitrite lead to the transition from HbO2 (Fe(2+) ) to MetHb
      (Fe(3+) ) in whole blood, and the iron atom converts from the low spin state to
      the high spin state with a delocalization from porphyrin plane. Moreover,
      multivariate statistical techniques, including principal components analysis
      (PCA) and linear discriminant analysis (LDA) are employed to develop effective
      diagnostic algorithms for classification of spectra between pure blood and
      poisoning blood. The diagnostic algorithms based on PCA-LDA yield a diagnostic
      sensitivity of 100% and specificity of 100% for separating poisoning blood from
      normal blood. Receiver operating characteristic (ROC) curve further confirms the
      effectiveness of the diagnostic algorithm based on PCA-LDA technique. The results
      from this study demonstrate that Raman spectroscopy combined with PCA-LDA
      algorithms has tremendous potential for the non-invasive detection of nitrite
      poisoning blood.

PMID- 24729433
TI  - Kaposi's Sarcoma in HIV-infected patients in South Africa: Multicohort study in
      the antiretroviral therapy era.
AB  - The incidence of Kaposi's Sarcoma (KS) is high in South Africa but the impact of
      antiretroviral therapy (ART) is not well defined. We examined incidence and
      survival of KS in HIV-infected patients enrolled in South African ART programs.
      We analyzed data of three ART programs: Khayelitsha township and Tygerberg
      Hospital programs in Cape Town and Themba Lethu program in Johannesburg. We
      included patients aged >16 years. ART was defined as a regimen of at least three
      drugs. We estimated incidence rates of KS for patients on ART and not on ART. We
      calculated Cox models adjusted for age, sex and time-updated CD4 cell counts and
      HIV-1 RNA. A total of 18,254 patients (median age 34.5 years, 64% female, median
      CD4 cell count at enrolment 105 cells/MUL) were included. During 37,488 person
      years follow-up 162 patients developed KS. The incidence was 1,682/100,000 person
      years (95% confidence interval [CI] 1,406-2,011) among patients not receiving ART
      and 138/100,000 person-years (95% CI 102-187) among patients on ART. The adjusted
      hazard ratio comparing time on ART with time not on ART was 0.19 (95% CI 0.13
      0.28). Low CD4 cell counts (time-updated) and male sex were also associated with
      KS. Estimated survival of KS patients at one year was 72.2% (95% CI 64.9-80.2)
      and higher in men than in women. The incidence of KS is substantially lower on
      ART than not on ART. Timely initiation of ART is essential to prevent KS and KS
      associated morbidity and mortality in South Africa and other regions in Africa
      with a high burden of HIV. 

PMID- 24729435
TI  - Role of social and individual experience in interaction of the meadow ant Formica
      pratensis (Hymenoptera: Formicidae) with ladybird imagines and hoverfly larvae.
AB  - The ability to recognize aphidophages is one of the key points in the protection
      ants provide aphids against their natural enemies. Behavior of honeydew
      collectors from nature ("field," control) and laboratory reared "naive" ants of
      Formica pratensis Retzius, which had never met either "mature" workers or aphids
      and aphidophages, was observed during their pairwise interactions with ladybird
      imagines and hoverfly larvae. The majority of the "naive" ants perceived
      ladybirds as an enemy at their first encounter attacking them immediately without
      any prior antennation. Ants seem to have a certain innate "enemy image" that lets
      them react very quickly to protect aphids. Hoverfly larvae were rarely attacked
      by both "field" and "naive" ants (>15%). During tests with ladybirds ants from
      nature attacked them and also demonstrated the most aggressive reactions (series
      of bites and "death grip") less frequently than the "naive" ants. The percentage
      of ants avoiding aphidophages after a contact with their chemical defense (reflex
      bleeding and glue-like saliva) was significantly higher in the control group.
      Whereas the "naive" ants did not learn to avoid danger, foragers from nature
      usually tried to avoid negative experience and used tactics of "short bites."
      Overall, experience has been proved to be unimportant for displaying key
      behavioral reactions underlying ant-ladybird interaction. However, accumulation
      of experience has been assumed to play an important role in the formation of
      behavioral strategy that allows honeydew collectors to drive aphidophages away
      with lower energy costs and avoid or minimize negative consequences of
      aphidophages' chemical defense. 

PMID- 24729436
TI  - Etiology and perinatal outcome of polyhydramnios.
AB  - PURPOSE: To determine causes of polyhydramnios and the respective perinatal
      outcome. MATERIALS AND METHODS: We retrospectively analyzed cases with
      polyhydramnios at the Medical University Graz, Austria from 2003 - 2011.
      Inclusion criteria were single deepest pocket >= 8  cm, amniotic fluid index >=
      25  cm, each of the latter parameters > 95th percentile or subjective impression.
      Etiologies, including TORCH infection, diabetes and congenital malformations, as
      well as perinatal outcome were evaluated. RESULTS: Out of 860 singleton
      pregnancies with polyhydramnios, 2.9 % had positive TORCH serology, 8.5 % had
      congenital anomalies, 19.8 % had maternal diabetes, and 68.8 % were idiopathic.
      The most common fetal anomalies were cardiac defects (32.9 %). Elective caesarean
      sections were more common in the groups with malformations and maternal diabetes.
      Low birth weight combined with severe polyhydramnios or maternal diabetes was
      associated with malformations. CONCLUSION: Diagnosis of polyhydramnios should
      prompt glucose-tolerance testing, detailed sonography including fetal
      echocardiography, and TORCH serology. Especially pregnancies with polyhydramnios
      and small fetuses as well as those with maternal diabetes should be carefully
      evaluated for malformations.

PMID- 24729437
TI  - Cardiac Adaptation of the Maternal Heart During Pregnancy: A Color-Coded Tissue
      Doppler Imaging Study--Feasibility, Reproducibility and Course during Pregnancy.
AB  - PURPOSE: Tissue Doppler imaging (TDI) allows the noninvasive quantification of
      global and regional myocardial function. Since there are changing loading
      conditions during pregnancy, this study aimed to determine maternal myocardial
      adaptation in normal pregnancy with TDI and tracking of the heart cycle. PATIENTS
      AND METHODS: 106 pregnant women, mean age of 33.4 years at baseline,
      prospectively underwent a total of 161 color-coded tissue Doppler
      echocardiography samples throughout pregnancy. In further offline analysis of the
      global and regional myocardial function of the basal segments, maximum tissue
      velocities at systole (Sm), in the early filling phase of diastole (Em) and
      during atrial contraction (Am) were assessed. RESULTS: From those stored samples,
      S-wave, E-wave and A-wave velocities could be obtained with a feasibility of 94.8
      % and with good inter- and intra-observer variability. S-wave velocity first
      showed an increase during early pregnancy followed by a decline to baseline
      characteristics at the 3 rd trimester. The E-wave velocity declined throughout
      pregnancy. The A-wave velocity increased continuously. These alterations result
      in a continuous decline of Em/Am ratio as pregnancy advances. CONCLUSION:
      Alterations in tissue velocities during pregnancy reflect maturational changes
      that mimic "diastolic dysfunction". Based on an understanding of those normal
      physiological changes, TDI may therefore assist in the monitoring and/or
      detecting of subclinical myocardial dysfunction during pregnancy.

PMID- 24729438
TI  - Accelerating spirocyclic polyketide synthesis using flow chemistry.
AB  - Over the past decade, the integration of synthetic chemistry with flow processing
      has resulted in a powerful platform for molecular assembly that is making an
      impact throughout the chemical community. Herein, we demonstrate the extension of
      these tools to encompass complex natural product synthesis. We have developed a
      number of novel flow-through processes for reactions commonly encountered in
      natural product synthesis programs to achieve the first total synthesis of
      spirodienal A and the preparation of spirangien A methyl ester. Highlights of the
      synthetic route include an iridium-catalyzed hydrogenation, iterative Roush
      crotylations, gold-catalyzed spiroketalization and a late-stage cis-selective
      reduction. 

PMID- 24729439
TI  - Borylation of unactivated aryl chlorides under mild conditions by using
      diisopropylaminoborane as a borylating reagent.
AB  - The synthesis of arylboronic ester derivatives from aryl chlorides by using
      aryl(amino)boranes is described. Palladium-catalyzed coupling between aryl
      chlorides and diisopropylaminoborane leads to the formation of a C?B bond under
      mild conditions. A wide range of functional groups are tolerated, making this
      method particularly useful for the borylation of functionalized aromatics. 

PMID- 24729440
TI  - Comparative anatomy, evolution, and homologies of tetrapod hindlimb muscles,
      comparison with forelimb muscles, and deconstruction of the forelimb-hindlimb
      serial homology hypothesis.
AB  - For more than two centuries, the idea that the forelimb and hindlimb are serially
      homologous structures has been accepted without serious question. This study
      presents the first detailed analysis of the evolution and homologies of all
      hindlimb muscles in representatives of each major tetrapod group and proposes a
      unifying nomenclature for these muscles. These data are compared with information
      obtained previously about the forelimb muscles of tetrapods and the muscles of
      other gnathostomes in order to address one of the most central and enigmatic
      questions in evolutionary and comparative anatomy: why are the pelvic and
      pectoral appendages of gnathostomes generally so similar to each other? An
      integrative analysis of the new myological data, combined with a review of recent
      paleontological, developmental, and genetic works and of older studies, does not
      support serial homology between the structures of these appendages. For instance,
      many of the strikingly similar forelimb and hindlimb muscles found in each major
      extant tetrapod taxon were acquired at different geological times and/or have
      different embryonic origins. These similar muscles are not serial homologues, but
      the result of evolutionary parallelism/convergence due to a complex interplay of
      ontogenetic, functional, topological, and phylogenetic constraints/factors.

PMID- 24729441
TI  - Rapid communication capturing the destabilizing effect of dihydrouridine through
      molecular simulations.
AB  - The structural effects of the commonly occurring modified nucleoside
      dihydrouridine (D) observed experimentally in model oligonucleotides include a
      strong destabilization of the C3'-endo sugar conformation of D, the disruption of
      stacking interactions of neighboring residues with D and a possible
      destabilization of the C3'-endo sugar pucker of the 5'-neighboring nucleoside.
      Our simulations with a combination of a set of parameters for modified RNA
      residues with the recently developed AMBER FF99chi force field having reoptimized
      glycosidic torsion angle parameters for standard nucleosides was found to
      reproduce the destabilizing effect of dihydrouridine better than with the AMBER
      FF99 force field for nucleic acids for which the parameters for the modified
      residues were originally developed.

PMID- 24729443
TI  - Corroboration of the prozone phenomenon in IgG4-related disease: comment on the
      article by Khosroshahi et al.

PMID- 24729442
TI  - Early memory formation disrupted by atypical PKC inhibitor ZIP in the medial
      prefrontal cortex but not hippocampus.
AB  - Atypical isoforms of protein kinase C (aPKCs; particularly protein kinase M zeta:
      PKMzeta) have been hypothesized to be necessary and sufficient for the
      maintenance of long-term potentiation (LTP) and long term memory by maintaining
      postsynaptic AMPA receptors via the GluA2 subunit. A myristoylated PKMzeta
      pseudosubstrate peptide (ZIP) blocks PKMzeta activity. We examined the actions of
      ZIP in medial prefrontal cortex (mPFC) and hippocampus in associative recognition
      memory in rats during early memory formation and memory maintenance. ZIP infusion
      in either hippocampus or mPFC impaired memory maintenance. However, early memory
      formation was impaired by ZIP in mPFC but not hippocampus; and blocking GluA2
      dependent removal of AMPA receptors did not affect this impairment caused by ZIP
      in the mPFC. The findings indicate: (i) a difference in the actions of ZIP in
      hippocampus and medial prefrontal cortex, and (ii) a GluA2-independent target of
      ZIP (possibly PKClambda) in the mPFC during early memory formation.

PMID- 24729444
TI  - Cerebrospinal fluid JC virus antibody index for diagnosis of natalizumab
      associated progressive multifocal leukoencephalopathy.
AB  - OBJECTIVE: Progressive multifocal leukoencephalopathy (PML), caused by JC virus
      (JCV), can occur in patients receiving natalizumab for multiple sclerosis (MS).
      JCV detection by quantitative polymerase chain reaction (qPCR) in cerebrospinal
      fluid (CSF), or brain biopsy, is required for probable or definite diagnosis of
      PML. However, in some patients only low levels of JCV DNA (<100 copies/ml) are
      present in CSF, making the diagnosis challenging. Our objective was to assess the
      complementary value of a CSF JCV antibody index (AIJCV ) in the diagnosis of
      natalizumab-associated PML. METHODS: AIJCV was assessed in 37 cases of
      natalizumab-associated PML and 89 MS-patients treated with natalizumab without
      PML. Sera and CSF were tested in a capture enzyme-linked immunosorbent assay,
      using JCV-VP1 fused to glutathione S-transferase as antigen. Albumin levels and
      total immunoglobulin G concentration were determined by immunonephelometry, and
      the AIJCV was calculated as published. RESULTS: Twenty-six of 37 (70%) patients
      with natalizumab-associated PML exhibited an AIJCV > 1.5, whereas this was seen
      in none of the controls (p < 0.0001). At time of the first positive qPCR for JCV
      DNA, 11 of 20 (55%) patients with natalizumab-associated PML had an AIJCV > 1.5.
      JCV DNA levels of <100 copies/ml were seen in 14 (70%) of these 20 patients, of
      whom 8 (57%) demonstrated an AIJCV > 1.5. INTERPRETATION: Determination of the
      AIJCV could be an added tool in the diagnostic workup for PML and should be
      included in the case definition of natalizumab-associated PML.

PMID- 24729445
TI  - Survival on treatment with second-line biologic therapy: a cohort study comparing
      cycling and swap strategies.
AB  - OBJECTIVE: The aim of this study was to evaluate the survival on treatment with
      second-line biologic therapy in RA patient non-responders to TNF inhibitors
      (TNFis) by comparing treatments with a second anti-TNF (cycling strategy) or with
      agents with a different mechanism of action (MoA; swap strategy). METHODS: RA
      patients treated with biologics since 1999 who stopped a first-line TNFi and
      started a second-line biotherapy were included in this cohort study. After
      adjusting for propensity scores, drug retention rates were calculated using the
      Kaplan-Meier method. The log-rank test was used to compare survival curves and
      the Cox regression model was used to compare risk for discontinuation between the
      two groups. RESULTS: Two hundred and one patients discontinued the first TNFi,
      switching to a second anti-TNF [n = 119 (59.2%)] or to abatacept [n = 26
      (31.7%)], rituximab [n = 40 (48.8%)] or tocilizumab [n = 15 (18.3%)]. Drug
      survival was significantly higher in the swap group than in the cycling group (P
      < 0.0001). After adjustment for propensity scores, probability of treatment
      retention in the swap group was significantly higher (hazard ratio = 2.258, 95%
      CI 1.507, 3.385), even after stratification according to the reason for the first
      TNFi discontinuation (P = 0.005). No significant differences emerged when
      comparing the retention rates of different MoAs (P = 0.51) in the swap group.
      CONCLUSION: In the clinical practice setting, the best option for managing TNFi
      non-responders seems to be swapping to a different MoA, with no differences
      between abatacept, rituximab and tocilizumab, irrespective of the reason for
      first TNFi discontinuation.

PMID- 24729446
TI  - Rituximab, a viable alternative for induction therapy of active lupus nephritis.

PMID- 24729447
TI  - Treatment of Wilms tumor using carboplatin compared to therapy without
      carboplatin.
AB  - BACKGROUND: Wilms tumor (WT) is the most common pediatric malignant primary renal
      tumor. One of the main drugs used in treatment is actinomycin-D. This was not
      readily available in Turkey at one time. Carboplatin was used in the primary
      treatment of WT in order to prevent delays in treatment. The aim of this study is
      to present the results of patients with WT receiving carboplatin or actinomycin-D
      therapy. PROCEDURE: Forty-eight consecutive patients with WT treated between July
      2005 and December 2011 were included in this retrospective study. The patients
      were treated according to Turkish Pediatric Oncology Group guidelines. Nineteen
      patients were treated with actinomycin-D and 29 with carboplatin (500 mg/m(2)
      /dose). The two groups were then compared in terms of 2- and 4-year overall
      survival (OS), event-free survival (EFS) and disease-free survival (DFS).
      RESULTS: Two- and four-year OS rates in the carboplatin group were 90.0% and
      90.0%, compared to 100.0% and 88.0%, respectively, in the non-carboplatin group.
      Two- and four-year EFS levels in the carboplatin group were 92.0% and 88.0%,
      respectively, compared to 82.0% and 76.0% in the non-carboplatin group. Two-and
      four-year DFS levels in the carboplatin group were 92.0% and 86.0%, respectively,
      compared to 77.0% and 77.0% in the non-carboplatin group. CONCLUSIONS: The
      findings show that the carboplatin can be used as an alternative drug in the
      primary treatment of WT in the event that actinomycin-D is unavailable or not
      tolerated.

PMID- 24729448
TI  - Sub-10-nm Pd nanosheets with renal clearance for efficient near-infrared
      photothermal cancer therapy.
AB  - Efficient renal clearance is of fundamentally important property of nanoparticles
      for their in vivo biomedical applications. In this work, we report the successful
      synthesis of ultra-small Pd nanosheets (SPNS) with an average diameter of 4.4 nm
      and their application in photothermal cancer therapy using a near infrared laser.
      The ultra-small Pd nanosheets have strong optical absorption in the NIR region
      and high photothermal conversion efficiency (52.0%) at 808 nm. After being
      surface-functionalized with reduced glutathione (GSH), the SPNS-GSH was
      administered to mice to investigate the biodistribution, photothermal efficacy
      and tumor ablation in vivo. The in vivo photothermal therapy studies clearly
      demonstrate that surface modification with GSH allows the nanosheets to exhibit
      prolonged blood circulation and thus high accumulation in tumors. Upon 808 nm NIR
      irradiation, the tumors can be completely ablated. More importantly, with the
      size below the renal filtration limit (<10 nm), the GSHylated Pd nanosheets can
      be nicely cleared from body through the renal excretion route and into urine.
      Together with the high efficacy of NIR photothermal therapy, the unique renal
      clearance properties make the ultra-small Pd nanosheets promising for practical
      use in photothermal cancer therapy. 

PMID- 24729449
TI  - Targeting ribosomal S6 kinases/Y-box binding protein-1 signaling improves
      cellular sensitivity to taxane in prostate cancer.
AB  - BACKGROUND: Taxanes are the only cytotoxic chemotherapeutic agents proved to
      prolong the survival in patients with castration-resistant prostate cancer.
      However, because of intrinsic and acquired resistances to taxanes, their
      therapeutical efficiencies are modest, bringing only a few months of survival
      benefit. Y-box binding protein-1 (YB-1) promotes cancer cell resistance to
      various anticancer treatments, including taxanes. Here, we aimed to elucidate the
      mechanism of taxane resistance by YB-1 and examined overcoming resistance by
      targeting YB-1 signaling. METHODS: Gene and protein expression levels were
      evaluated by quantitative real-time polymerase chain reaction and Western blot
      analysis, respectively. We evaluated the sensitivity of prostate cancer cells to
      taxanes using cytotoxicity assays. RESULTS: Natural taxane paclitaxel from Taxus
      brevifolia activated the Raf-1/extracellular signal-regulated kinase (ERK)
      pathway, leading to an activation of ribosomal S6 kinases (RSK)/YB-1 signaling.
      Activated Raf-1/ERK pathway was blunted by YB-1 knockdown in prostate cancer
      cells, indicating regulation between Raf-1/ERK signaling and YB-1. In addition,
      ERK or RSK was activated in taxane-resistant prostate cancer cells, resulting in
      YB-1 activation. YB-1 knockdown as well as RSK inhibition using RSK-specific
      siRNA or the small molecule inhibitor SL0101 successfully blocked activation of
      YB-1, leading to suppression of prostate cancer growth and sensitization to
      paclitaxel. CONCLUSIONS: Taken together, these findings indicate that RSK/YB-1
      signaling contributes to taxane resistance, and implicate the therapeutics
      targeting RSK/YB-1 signaling such as RSK inhibitor as a promising novel therapy
      against prostate cancer, especially in combination with taxane.

PMID- 24729450
TI  - De novo mutation in the GNAL gene causing seemingly sporadic dystonia in a
      Serbian patient.
AB  - BACKGROUND: Mutations in GNAL (DYT25) have recently been established as the first
      confirmed cause of focal or segmental adult-onset dystonia. Mutation carriers
      show craniocervical involvement; however, the GNAL mutational and phenotypic
      spectrum remain to be further characterized, and guidelines for diagnostic
      testing need to be established. METHODS: The authors used Sanger sequencing to
      test for changes in the GNAL coding or splice-site regions in 236 Serbian
      patients suffering from isolated dystonia with craniocervical involvement.
      RESULTS: One novel likely pathogenic substitution (c.1061T>C; p.Val354Ala) in
      GNAL was detected in a sporadic cervical dystonia patient (mutation frequency:
      0.4%). This mutation was not present in the DNA of either parent, despite
      confirmed parentage. CONCLUSIONS: This is the first report of a de novo GNAL
      mutation causing genetically proven, seemingly sporadic DYT25 dystonia. Our
      finding highlights the importance of genetic testing for GNAL mutations in
      establishing the molecular diagnosis even for patients with a negative family
      history.

PMID- 24729451
TI  - Multiple effects of the special AT-rich binding protein 1 (SATB1) in colon
      carcinoma.
AB  - SATB1 (special AT-rich binding protein 1) is a global chromatin organizer
      regulating the expression of a large number of genes. Overexpression has been
      found in various solid tumors and positively correlated with prognostic and
      clinicopathological properties. In colorectal cancer (CRC), SATB1 overexpression
      and its correlation with poor differentiation, invasive depth, TNM (tumor, nodes,
      metastases) stage and prognosis have been demonstrated. However, more detailed
      studies on the SATB1 functions in CRC are warranted. In this article, we
      comprehensively analyze the cellular and molecular role of SATB1 in CRC cell
      lines with different SATB1 expression levels by using RNAi-mediated knockdown.
      Using siRNAs with different knockdown efficacies, we demonstrate
      antiproliferative, cell cycle-inhibitory and proapoptotic effects of SATB1
      knockdown in a SATB1 gene dose-dependent manner. Tumor growth inhibition is
      confirmed in vivo in a subcutaneous tumor xenograft mouse model using stable
      knockdown cells. The in-depth analysis of cellular effects reveals increased
      activities of caspases-3, -7, -8, -9 and other mediators of apoptotic pathways.
      Similarly, the analysis of E- and N-cadherin, slug, twist, beta-catenin and MMP7
      indicates SATB1 effects on epithelial-mesenchymal transition (EMT) and matrix
      breakdown. Our results also establish SATB1 effects on receptor tyrosine kinases
      and (proto-)oncogenes such as HER receptors and Pim-1. Taken together, this
      suggests a more complex molecular interplay between tumor-promoting and possible
      inhibitory effects in CRC by affecting multiple pathways and molecules involved
      in proliferation, cell cycle, EMT, invasion and cell survival. 

PMID- 24729452
TI  - Mechanically interlocked single-wall carbon nanotubes.
AB  - Extensive research has been devoted to the chemical manipulation of carbon
      nanotubes. The attachment of molecular fragments through covalent-bond formation
      produces kinetically stable products, but implies the saturation of some of the C
      C double bonds of the nanotubes. Supramolecular modification maintains the
      structure of the SWNTs but yields labile species. Herein, we present a strategy
      for the synthesis of mechanically interlocked derivatives of SWNTs (MINTs). In
      the key rotaxane-forming step, we employed macrocycle precursors equipped with
      two pi-extended tetrathiafulvalene SWNT recognition units and terminated with
      bisalkenes that were closed around the nanotubes through ring-closing metathesis
      (RCM). The mechanically interlocked nature of the derivatives was probed by
      analytical, spectroscopic, and microscopic techniques, as well as by appropriate
      control experiments. Individual macrocycles were observed by HR STEM to
      circumscribe the nanotubes.

PMID- 24729454
TI  - Integrating 31P DOSY NMR spectroscopy and molecular mechanics as a powerful tool
      for unraveling the chemical structures of polyoxomolybdate-based amphiphilic
      nanohybrids in aqueous solution.
AB  - Novel organic-inorganic hybrids of various sizes were generated by reaction of
      1,8-octanediphosphonic acid (ODP) and (NH4)6Mo7O24 in aqueous solution. The
      formation of rodlike hybrids with variable numbers of covalently bound ODP and
      polyoxomolybdate (POM) units can be tuned as a function of increasing
      (NH4)6Mo7O24 concentration at fixed ODP concentration. The chemical structure of
      the ODP/POM hybrids was characterized by (1)H, (31)P, and (95)Mo NMR
      spectroscopy. Heteronuclear (31)P DOSY (diffusion- ordered NMR spectroscopy) and
      molecular mechanics (MM) calculations were applied to determine the size and
      shape of the nanosized hybrids generated at various ODP/POM ratios. For this
      purpose, the structures of ODP/POM hybrids with variable numbers of ODP and POM
      units were optimized by MM and then approximated as cylinder-shaped objects by
      using a recently described mathematical algorithm. The thus-obtained cylinder
      length and diameter were further used to calculate the expected diffusion
      coefficients of the ODP/POM hybrids. Comparison of the calculated and
      experimentally determined diffusion coefficients led to the most probable ODP/POM
      hybrid length for each sample composition. The (31)P DOSY results show that the
      length of the hybrids increases with increasing POM concentration and reaches a
      maximum corresponding to an average of 8 ODP/7 POM units per chain at a sample
      composition of 20 mM ODP and 14 mM POM. With excess POM, above the latter
      concentration, the formation of shorter-chain hybrids terminated by Mo7 clusters
      at one or both ends was evidenced on further increasing the POM concentration.
      The results demonstrate that the combination of (31)P DOSY and MM, although
      virtually unexplored in POM chemistry, is a powerful innovative strategy for the
      detailed characterization of nanosized organic-inorganic POM-based hybrids in
      solution.

PMID- 24729455
TI  - Reply: To PMID 24431286.

PMID- 24729456
TI  - Fluorine-containing 6,7-dialkoxybiaryl-based inhibitors for phosphodiesterase 10
      A: synthesis and in vitro evaluation of inhibitory potency, selectivity, and
      metabolism.
AB  - Based on the potent phosphodiesterase 10 A (PDE10A) inhibitor PQ-10, we
      synthesized 32 derivatives to determine relationships between their molecular
      structure and binding properties. Their roles as potential positron emission
      tomography (PET) ligands were evaluated, as well as their inhibitory potency
      toward PDE10A and other PDEs, and their metabolic stability was determined in
      vitro. According to our findings, halo-alkyl substituents at position 2 of the
      quinazoline moiety and/or halo-alkyloxy substituents at positions 6 or 7 affect
      not only the compounds' affinity, but also their selectivity toward PDE10A. As a
      result of substituting the methoxy group for a monofluoroethoxy or difluoroethoxy
      group at position 6 of the quinazoline ring, the selectivity for PDE10A over
      PDE3A increased. The same result was obtained by 6,7-difluoride substitution on
      the quinoxaline moiety. Finally, fluorinated compounds (R)-7-(fluoromethoxy)-6
      methoxy-4-(3-(quinoxaline-2-yloxy)pyrrolidine-1-yl)quinazoline (16 a), 19 a-d,
      (R)-tert-butyl-3-(6-fluoroquinoxalin-2-yloxy)pyrrolidine-1-carboxylate (29), and
      35 (IC50 PDE10A 11-65 nM) showed the highest inhibitory potential. Further,
      fluoroethoxy substitution at position 7 of the quinazoline ring improved
      metabolic stability over that of the lead structure PQ-10. 

PMID- 24729457
TI  - Quality of life in cancer rehabilitation: the role of life goal adjustment.
AB  - OBJECTIVE: A cancer diagnosis affects patients' quality of life (QOL) as well as
      their pursuit of life goals. However, numerous studies have shown surprisingly
      stable QOL measures in cancer patients over time. We propose that life goal
      adjustment can act as the missing link in explaining this response shift. Thus,
      the aim of this study was to examine associations between life goal adjustment
      and patients' QOL at baseline and over the course of 20 months. METHODS: Eighty
      six cancer patients were recruited during rehabilitation and reassessed at follow
      up 20 months later. Life goals were measured using the Life Goals Questionnaire
      and analyzed in relation to global QOL as assessed with the World Health
      Organization Quality of Life Questionnaire - Short Form. RESULTS: The overall
      attainment of life goals was associated with QOL. Moreover, over a period of 20
      months, perceived QOL and goal attainment remained stable, whereas importance of
      life goals decreased. Lesser importance and improved goal attainment were
      predictors of increases in QOL. CONCLUSIONS: Results suggest that downgrading
      unattainable goals and making more progress in accomplishing attainable goals may
      be possible mechanisms of response shift as an adaption to illness. Thus,
      integrating life goal adjustment into rehabilitation services for cancer patients
      seems to be worthwhile to enhance an adaptive self-regulation and QOL.

PMID- 24729458
TI  - Synthesis and antibacterial and cytotoxic activities of new N-3 substituted
      thiazolidine-2,4-dione derivatives bearing the pyrazole moiety.
AB  - Two new series of N-3 substituted thiazolidine-2,4-dione derivatives bearing the
      pyrazole moiety (5a-j and 7a-j) were synthesized and assessed in vitro for their
      efficacy as antibacterial agents against gram-positive and gram-negative
      bacterial strains. Among the tested compounds, 7b, 7c, 7i, and 7j were found to
      be active against gram-positive bacteria (Staphylococcus aureus and Streptococcus
      pyogenes) with minimum inhibitory concentration (MIC) values in the range of 6.25
      25 ug/mL, and some compounds were also tested against methicillin-resistant S.
      aureus (MRSA). Compounds 7c and 7j inhibited the growth of MRSA at MIC values of
      6.25 and 12.5 ug/mL, respectively. The influence of the lipophilicity (C log P)
      on the biological profile (MIC) of the prepared products was also discussed. From
      the standpoint of structure-activity relationship studies, it was observed that
      the lipophilic profiles of the compounds were crucial for their antibacterial
      activities. Further, the results of the MTT cytotoxicity studies on a human
      cervical cancer cell line (HeLa) and a mouse embryonic fibroblast cell line (NIH
      3T3) suggested that compounds 7b, 7c, 7i, and 7j were endowed with low levels of
      cytotoxicity.

PMID- 24729459
TI  - Synthesis and solid-state structures of a tetrathiafulvalene-conjugated
      bistetracene.
AB  - A tetrathiafulvalene (TTF)-conjugated bistetracene was synthesized and
      characterized in the molecular electronic structures based on the spectroscopic
      measurements and the single-crystal X-ray diffraction analysis. UV/Vis absorption
      and electrochemical measurements of 5 revealed the considerable electronic
      communication between two tetracenedithiole units by through-bond and/or through
      space interactions. The difference in the crystal-packing structures of 5,
      showing polymorphism, results in a variety of intermolecular electronic-coupling
      pattern. Of these, the pi-stacking structure of 5 A gave a large transfer
      integral of HOMOs (97 meV), which value is beyond hexacene and rubrene, thus,
      quite beneficial to achieve the high hole mobility. 

PMID- 24729460
TI  - On the tracks of Nitrogen deposition effects on temperate forests at their
      southern European range - an observational study from Italy.
AB  - We studied forest monitoring data collected at permanent plots in Italy over the
      period 2000-2009 to identify the possible impact of nitrogen (N) deposition on
      soil chemistry, tree nutrition and growth. Average N throughfall (N-NO3 +N-NH4 )
      ranged between 4 and 29 kg ha(-1)  yr(-1) , with Critical Loads (CLs) for
      nutrient N exceeded at several sites. Evidence is consistent in pointing out
      effects of N deposition on soil and tree nutrition: topsoil exchangeable base
      cations (BCE) and pH decreased with increasing N deposition, and foliar nutrient
      N ratios (especially N : P and N : K) increased. Comparison between bulk
      openfield and throughfall data suggested possible canopy uptake of N, levelling
      out for bulk deposition >4-6 kg ha(-1)  yr(-1) . Partial Least Square (PLS)
      regression revealed that - although stand and meteorological variables explained
      the largest portion of variance in relative basal area increment (BAIrel 2000
      2009) - N-related predictors (topsoil BCE, C : N, pH; foliar N-ratios; N
      deposition) nearly always improved the BAIrel model in terms of variance
      explained (from 78.2 to 93.5%) and error (from 2.98 to 1.50%). N deposition was
      the strongest predictor even when stand, management and atmosphere-related
      variables (meteorology and tropospheric ozone) were accounted for. The maximal
      annual response of BAIrel was estimated at 0.074-0.085% for every additional kgN.
      This corresponds to an annual maximal relative increase of 0.13-0.14% of carbon
      sequestered in the above-ground woody biomass for every additional kgN, i.e. a
      median value of 159 kgC per kgN ha(-1)  yr(-1) (range: 50-504 kgC per kgN,
      depending on the site). Positive growth response occurred also at sites where
      signals of possible, perhaps recent N saturation were detected. This may suggest
      a time lag for detrimental N effects, but also that, under continuous high N
      input, the reported positive growth response may be not sustainable in the long
      term. 

PMID- 24729461
TI  - Iridium-catalyzed enantioselective C-H alkylation of ferrocenes with alkenes
      using chiral diene ligands.
AB  - The first catalytic and enantioselective C-H alkylation of ferrocene derivatives
      with various alkenes was achieved. A cationic iridium complex, having a chiral
      diene ligand, and an isoquinolyl moiety as a directing group are essential for
      regioselective and enantioselective C-H bond activation.

PMID- 24729462
TI  - A population-based study of retinoblastoma incidence and survival in Argentine
      children.
AB  - BACKGROUND: An increased incidence of retinoblastoma in some developing countries
      has been reported but no conclusive data are available from population-based
      studies at national level. PURPOSE: To report the incidence and survival of
      retinoblastoma in Argentina from the National Pediatric Cancer Registry (ROHA)
      and the influence of socio-economical indicators on outcome. PROCEDURE: Cases
      reported to the ROHA (2000-2009) were analyzed. Incidence rates were calculated
      using National Vital Statistics and survival was estimated. The extended human
      development index (EHDI) was used as a socio-economical indicator. RESULTS: With
      438 patients reported, an incidence of 5.0 cases per million children 0-14 years
      old (95% CI 3.5-6.4) was calculated. Median age at diagnosis was significantly
      higher for children from provinces with lower EHDI; (24 vs. 35 months for
      unilateral, (P = 0.003) and 9 versus 11.5 months for bilateral retinoblastoma (P
      = 0.027). The 3-year probability of survival was 0.87 and 0.94 for unilateral and
      bilateral retinoblastoma, respectively. Residents in provinces with higher EHDI
      had a better 3-year survival (0.93 vs. 0.77 for lower EHDI, P < 0.0001).
      Probability of survival was higher for patients treated at tertiary level
      institutions (P = 0.0015). The combination of low EHDI residence province with no
      treatment at a tertiary institution was associated with the worst survival
      outcome. For both, unilateral and bilateral disease, children who died were in
      average diagnosed at older age. CONCLUSIONS: The incidence of retinoblastoma in
      Argentina is comparable to that of developed countries. Retinoblastoma is
      diagnosed later and survival is lower in the less developed areas of the country.

PMID- 24729463
TI  - Indium selenides: structural characteristics, synthesis and their thermoelectric
      performances.
AB  - Indium selenides have attracted extensive attention in high-efficiency
      thermoelectrics for waste heat energy conversion due to their extraordinary and
      tunable electrical and thermal properties. This Review aims to provide a thorough
      summary of the structural characteristics (e.g. crystal structures, phase
      transformations, and structural vacancies) and synthetic methods (e.g. bulk
      materials, thin films, and nanostructures) of various indium selenides, and then
      summarize the recent progress on exploring indium selenides as high-efficiency
      thermoelectric materials. By highlighting challenges and opportunities in the
      end, this Review intends to shine some light on the possible approaches for
      thermoelectric performance enhancement of indium selenides, which should open up
      an opportunity for applying indium selenides in the next-generation
      thermoelectric devices. 

PMID- 24729464
TI  - Design, synthesis and anticancer activity evaluation of some novel pyrrolo[1,2
      a]azepine derivatives.
AB  - A novel series of pyrrolo[1,2-a]azepine derivatives 3-7 were synthesized and
      their structures were confirmed by spectral and elemental analyses. Antitumor
      activity evaluation of these compounds was carried out against liver (HepG2),
      breast (MCF7), and colon (HCT116) cancer cell lines using the sulforhodamine-B
      (SRB) assay method and doxorubicin as reference standard. Compounds 3 and 6 were
      found to be more potent than doxorubicin against HepG2 cells, with IC50 values of
      4, 1.6 and 10.8 nM, respectively. Moreover, compounds 3 and 7 showed broad
      spectrum anticancer activity against all the tested cell lines, and their IC50
      values were in the nanomolar range (4-44.2 nM and 20.7-45.4 nM, respectively).
      The 2-benzoylamino derivative of pyrrolo[1,2-a]azepine 5b was the most potent one
      against MCF7 cells (IC50 of 10.7 nM); however, the 2-(2-chloro-acetylamino)
      pyrroloazepine derivative 6 was the most potent against the HCT116 cell line,
      with an IC50 value of 21.1 nM. The novel compounds were docked into the active
      site of cyclin-dependent kinase 2 (CDK2) to explore the ability of these
      compounds to interact with these kinases. All compounds showed a lower binding
      score energy than the reference ligand.

PMID- 24729465
TI  - G-quadruplex structures and their interaction diversity with ligands.
AB  - G-Quadruplexes are distinct nucleic acid secondary structures that are formed
      from G-rich DNA and RNA sequences; they are built around successive G-tetrads of
      Hoogsteen hydrogen-bonded guanine bases. The existence of G-quadruplex structures
      has been confirmed in the human telomere and genome, and their biological
      functions have been demonstrated. Thus, the prospect of using G-quadruplex
      structures as a novel target for drug design is important. This review focuses on
      structural polymorphism of G-quadruplexes on the basis of the classification of
      the strand number of the G-quadruplex formed and its interaction diversity with
      small molecules (G4-ligands) that display high affinity and, more importantly,
      selectivity. Also, we outlook some future challenges for G-quadruplex structure
      and ligand studies. Such information, together with the biological functions of
      for G-quadruplex, will be of crucial importance for the research and development
      of drugs that target G-quadruplexes formed from particular genes and human
      telomeres. 

PMID- 24729466
TI  - Low-dose irinotecan improves advanced lupus nephritis in mice potentially by
      changing DNA relaxation and anti-double-stranded DNA binding.
AB  - OBJECTIVE: Despite clear advances in the treatment of systemic lupus
      erythematosus (SLE), many patients still present with refractory lupus nephritis,
      requiring new treatment strategies for this disease. This study was undertaken to
      determine whether reduced doses of the topoisomerase I (topo I) inhibitor
      irinotecan, which is known as a chemotherapeutic agent, suppress SLE in (NZB *
      NZW)F1 (NZB/NZW) mice, and to evaluate the potential mechanism by which
      irinotecan influences the course of SLE. METHODS: NZB/NZW mice were treated with
      low-dose irinotecan beginning at either 24 weeks of age or established
      glomerulonephritis, defined as proteinuria of grade >=3+. Binding of anti-double
      stranded DNA (anti-dsDNA) antibodies was measured by enzyme-linked immunosorbent
      assay (ELISA), and DNA relaxation was visualized by gel electrophoresis. RESULTS:
      Significantly reduced irinotecan doses improved lupus nephritis and prolonged
      survival in NZB/NZW mice. The lowest dose successfully used for the treatment of
      established murine lupus nephritis was >50 times lower than the dose usually used
      for chemotherapy in humans. As a mechanism, low-dose irinotecan reduced B cell
      activity. However, the levels of B cell activity in irinotecan-treated mice were
      similar to those in BALB/c mice of the same age, suggesting that irinotecan did
      not induce clear immunosuppression. In addition, incubation of dsDNA with topo I
      increased binding of murine and human anti-dsDNA antibodies, showing for the
      first time that relaxed DNA is more susceptible to anti-dsDNA antibody binding.
      This effect was reversed by addition of the topo I inhibitor camptothecin.
      CONCLUSION: Our findings indicate that topo I inhibition may be a novel and
      targeted therapy for SLE.

PMID- 24729467
TI  - Analysis of flow changes in side branches jailed by flow diverters in rabbit
      models.
AB  - Understanding the flow alteration in side branches during flow diversion
      treatment of cerebral aneurysms is important to prevent ischemic complications
      and improve device designs. Flow diverters were placed in the aorta of four
      rabbits crossing the origin of side arteries. Subject-specific computational
      models were constructed from 3D angiographies and Doppler ultrasounds (DUSs).
      Flow simulations were run before and after virtually deploying the flow
      diverters, assuming distal resistances remained unchanged after treatment. All
      jailed arteries remained patent angiographically 8 weeks after treatment. The
      computational models estimated decreases compared to pretreatment in the mean
      flow rates between 2% and 20% and in peak flow rates between 5% and 36%. The
      major changes were observed during systole. Flow patterns did not exhibit
      recirculation zones before treatment. Implantation of the flow diverters altered
      the flow structure only locally near the device wires. No major recirculation
      regions were created or destroyed. Flow diverters seem safe with respect to
      perforator or side branch occlusion. Relatively small changes in flow rates
      through jailed arteries are expected, even for moderate to large degrees of
      coverage of their origins. These results seem consistent with previous clinical
      experiences where no or very few complications related to perforator occlusion
      have been reported.

PMID- 24729468
TI  - Experimental and theoretical studies on arene-bridged metal-metal-bonded
      dimolybdenum complexes.
AB  - The bis(hydride) dimolybdenum complex, [Mo2(H)2{HC(N-2,6-iPr2C6H3)2}2(thf)2], 2,
      which possesses a quadruply bonded Mo2(II) core, undergoes light-induced (365 nm)
      reductive elimination of H2 and arene coordination in benzene and toluene
      solutions, with formation of the Mo(I)2 complexes [Mo2{HC(N-2,6
      iPr2C6H3)2}2(arene)], 3?C6H6 and 3?C6H5Me, respectively. The analogous C6H5OMe, p
      C6H4Me2, C6H5F, and p-C6H4F2 derivatives have also been prepared by thermal or
      photochemical methods, which nevertheless employ different Mo2 complex
      precursors. X-ray crystallography and solution NMR studies demonstrate that the
      molecule of the arene bridges the molybdenum atoms of the Mo(I)2 core,
      coordinating to each in an eta(2) fashion. In solution, the arene rotates fast on
      the NMR timescale around the Mo2-arene axis. For the substituted aromatic
      hydrocarbons, the NMR data are consistent with the existence of a major rotamer
      in which the metal atoms are coordinated to the more electron-rich C-C bonds.

PMID- 24729469
TI  - Mining of public sequencing databases supports a non-dietary origin for putative
      foreign miRNAs: underestimated effects of contamination in NGS.
AB  - The report that exogenous plant miRNAs are able to cross the mammalian
      gastrointestinal tract and exert gene-regulation mechanism in mammalian tissues
      has yielded a lot of controversy, both in the public press and the scientific
      literature. Despite the initial enthusiasm, reproducibility of these results was
      recently questioned by several authors. To analyze the causes of this unease, we
      searched for diet-derived miRNAs in deep-sequencing libraries performed by
      ourselves and others. We found variable amounts of plant miRNAs in publicly
      available small RNA-seq data sets of human tissues. In human spermatozoa,
      exogenous RNAs reached extreme, biologically meaningless levels. On the contrary,
      plant miRNAs were not detected in our sequencing of human sperm cells, which was
      performed in the absence of any known sources of plant contamination. We designed
      an experiment to show that cross-contamination during library preparation is a
      source of exogenous RNAs. These contamination-derived exogenous sequences even
      resisted oxidation with sodium periodate. To test the assumption that diet
      derived miRNAs were actually contamination-derived, we sought in the literature
      for previous sequencing reports performed by the same group which reported the
      initial finding. We analyzed the spectra of plant miRNAs in a small RNA
      sequencing study performed in amphioxus by this group in 2009 and we found a very
      strong correlation with the plant miRNAs which they later reported in human sera.
      Even though contamination with exogenous sequences may be easy to detect, cross
      contamination between samples from the same organism can go completely unnoticed,
      possibly affecting conclusions derived from NGS transcriptomics. 

PMID- 24729471
TI  - Validation of the Freund Clock Drawing Test as a screening tool to detect
      cognitive dysfunction in elderly cancer patients undergoing comprehensive
      geriatric assessment.
AB  - OBJECTIVE: We aimed to validate the Freund Clock Drawing Test (CDT), with its
      predefined cutoff score of <=4, as a screening tool to detect elderly cancer
      patients in need of a more in-depth cognitive evaluation within a comprehensive
      geriatric assessment (CGA). METHODS: Patients aged 70 years or older with a
      histologically confirmed diagnosis of cancer were evaluated with a full CGA,
      including CDT and Folstein Mini Mental State Examination (MMSE) as gold standard.
      Validation of the Freund CDT was defined in terms of diagnostic accuracy of the
      test through receiver operating characteristics (ROC)-analysis. To accept the
      Freund CDT as a screening tool, we estimated that the area under the ROC curve
      (AUC) had to differ significantly from 0.70 with an AUC of at least 0.85.
      RESULTS: Two hundred elderly cancer patients with a mean age of 79.0 years were
      included. Four patients were excluded from the analyses because of invalid
      results. Potential cognitive impairment (MMSE <=23) was observed in 27.0% of
      patients. Based on of the AUC +/- SE, the Freund CDT showed excellent diagnostic
      performance (0.95 +/- 0.17). Furthermore, it provided excellent sensitivity
      (94.3%) and high specificity (87.4%). CONCLUSIONS: Our results indicate that the
      Freund CDT can be used as an initial screening tool to detect elderly cancer
      patients in need of a more in-depth cognitive assessment within CGA, instead of
      the MMSE.

PMID- 24729472
TI  - Boron perturbed click reactions prompt aromatic C-H activations.
AB  - The reaction of boron alkynes and boron azides leads to rare N3BC heterocycles
      resulting from aromatic C-H activation of benzene and toluene. While subsequent
      treatment with PMe3 gave the P-B adduct with the exocyclic boron, reaction with
      PtBu3 effected deprotonation of the heterocycle to give the corresponding
      phosphonium salt.

PMID- 24729473
TI  - Infectious disease testing for cellular therapy.

PMID- 24729470
TI  - Analysis of global changes in gene expression induced by human polynucleotide
      phosphorylase (hPNPase(old-35)).
AB  - As a strategy to identify gene expression changes affected by human
      polynucleotide phosphorylase (hPNPase(old-35)), we performed gene expression
      analysis of HeLa cells in which hPNPase(old-35) was overexpressed. The observed
      changes were then compared to those of HO-1 melanoma cells in which hPNPase(old
      35) was stably knocked down. Through this analysis, 90 transcripts, which
      positively or negatively correlated with hPNPase(old-35) expression, were
      identified. The majority of these genes were associated with cell communication,
      cell cycle, and chromosomal organization gene ontology categories. For a number
      of these genes, the positive or negative correlations with hPNPase(old-35)
      expression were consistent with transcriptional data extracted from the TCGA (The
      Cancer Genome Atlas) expression datasets for colon adenocarcinoma (COAD), skin
      cutaneous melanoma (SKCM), ovarian serous cyst adenocarcinoma (OV), and prostate
      adenocarcinoma (PRAD). Further analysis comparing the gene expression changes
      between Ad.hPNPase(old-35) infected HO-1 melanoma cells and HeLa cells
      overexpressing hPNPase(old-35) under the control of a doxycycline-inducible
      promoter, revealed global changes in genes involved in cell cycle and mitosis.
      Overall, this study provides further evidence that hPNPase(old-35) is associated
      with global changes in cell cycle-associated genes and identifies potential gene
      targets for future investigation.

PMID- 24729474
TI  - Effects of copper exposure on hatching success and early larval survival in
      marbled salamanders, Ambystoma opacum.
AB  - The creation of wetlands, such as urban and industrial ponds, has increased in
      recent decades, and these wetlands often become enriched in pollutants over time.
      One metal contaminant trapped in created wetlands is copper (Cu(2+)). Copper
      concentrations in sediments and overlying water may affect amphibian species that
      breed in created wetlands. The authors analyzed the Cu concentration in dried
      sediments from a contaminated wetland and the levels of aqueous Cu released after
      flooding the sediments with different volumes of water, mimicking low, medium,
      and high pond-filling events. Eggs and larvae of Ambystoma opacum Gravenhorst, a
      salamander that lays eggs on the sediments in dry pond beds that hatch on pond
      filling, were exposed to a range of Cu concentrations that bracketed potential
      aqueous Cu levels in created wetlands. Embryo survival varied among clutches, but
      increased Cu levels did not affect embryo survival. At Cu concentrations of 500
      ug/L or greater, however, embryos hatched earlier, and the aquatic larvae died
      shortly after hatching. Because Cu concentrations in sediments increase over time
      in created wetlands, even relatively tolerant species such as A. opacum may be
      affected by Cu levels in the posthatching environment.

PMID- 24729475
TI  - Patterns of climate-induced density shifts of species: poleward shifts faster in
      northern boreal birds than in southern birds.
AB  - Climate change has been shown to cause poleward range shifts of species. These
      shifts are typically demonstrated using presence-absence data, which can mask the
      potential changes in the abundance of species. Moreover, changes in the mean
      centre of weighted density of species are seldom examined, and comparisons
      between these two methods are even rarer. Here, we studied the change in the mean
      weighted latitude of density (MWLD) of 94 bird species in Finland, northern
      Europe, using data covering a north-south gradient of over 1000 km from the 1970s
      to the 2010s. The MWLD shifted northward on average 1.26 km yr(-1) , and this
      shift was significantly stronger in northern species compared to southern
      species. These shifts can be related to climate warming during the study period,
      because the annual temperature had increased more in northern Finland (by 1.7 
      degrees C) than in southern Finland (by 1.4  degrees C), although direct causal
      links cannot be shown. Density shifts of species distributed over the whole
      country did not differ from shifts in species situated on the edge of the species
      range in southern and northern species. This means that density shifts occur both
      in the core and on the edge of species distribution. The species-specific
      comparison of MWLD values with corresponding changes in the mean weighted
      latitude using presence-absence atlas data (MWL) revealed that the MWLD moved
      more slowly than the MWL in the atlas data in the southern species examined, but
      more rapidly in the northern species. Our findings highlight that population
      densities are also moving rapidly towards the poles and the use of presence
      absence data can mask the shift of population densities. We encourage use of
      abundance data in studies considering the effects of climate change on
      biodiversity.

PMID- 24729476
TI  - Intelligent and ultrasensitive analysis of mercury trace contaminants via
      plasmonic metamaterial-based surface-enhanced Raman spectroscopy.
AB  - Label-free molecular logic gates (AND, INHIBIT, and OR) are constructed based on
      specific conformation modulation of a guanine- and thymine-rich DNA, while the
      optical readout is enabled by the tunable metamaterials which serve as a
      substrate for surface enhanced Raman spectroscopy. The DNA logic is simple to
      operate, highly reproducible, and can be stimulated by ultra-low concentration of
      the external inputs, enabling an extremely sensitive detection of mercury ions
      down to 2 * 10(-4) ppb. 

PMID- 24729477
TI  - Total synthesis of anticoagulant pentasaccharide fondaparinux.
AB  - The anticoagulant pentasaccharide fondaparinux was synthesized using an improved
      and optimized synthetic strategy including a convergent [3+2] coupling approach,
      orthogonal protecting groups and various glycosyl donors. The new methods of
      glycosylation were also used for controlling the stereochemical configuration and
      improving the yield of the glycosylation. In addition, HPLC and NMR methods to
      monitor the process of total synthesis of fondaparinux were employed. This work
      provides a comprehensive elaboration for the synthesis and analysis of
      fondaparinux based on related literature, as well as abundant information for the
      synthesis of heparin-like oligosaccharides. 

PMID- 24729478
TI  - Regulatory B10 cells are decreased in patients with rheumatoid arthritis and are
      inversely correlated with disease activity.
AB  - OBJECTIVE: Regulatory interleukin-10 (IL-10)-producing B cells (B10 cells) have
      been shown to prevent and cure collagen-induced arthritis in mice. In humans,
      very little is known about B10 cells in rheumatoid arthritis (RA). Several B cell
      subsets, such as CD24(high) CD38(high) , CD24(high) CD27+, and CD5+ B cells, were
      suggested to be precursors of B10 cells. We aimed to analyze these B cell subsets
      and B10 cells in RA patients and healthy controls. METHODS: B10 cells were
      generated from peripheral blood mononuclear cells stimulated for 24 hours with
      CpG and for 4 hours with phorbol 12-myristate 13-acetate/ionomycin/brefeldin A.
      Intracellular B cell IL-10 was assessed by flow cytometry. Thirty-one controls
      and 99 RA patients were included. RESULTS: After multiple adjustments, levels of
      CD24(high) CD38(high) , CD24(high) CD27+, and CD5+ B cells were found to be
      similar in RA patients and controls. Levels of B10 cells were lower in RA
      patients than in controls, especially in patients with RA of <=5 years' duration.
      Levels of B10 cells correlated inversely with the Disease Activity Score in 28
      joints. This was more pronounced in patients with RA of <=5 years' duration, in
      whom B10 cells also correlated inversely with C-reactive protein levels.
      Moreover, B10 cells correlated inversely with rheumatoid factor levels.
      CD24(high) CD38(high) and CD24(high) CD27+ B cells induced more Treg cells than
      did CD24(low) B cells in controls but not in RA patients. CONCLUSION: The ability
      of B cells to produce IL-10 was altered in RA, and this impairment influenced
      disease activity, biologic inflammation, and autoantibody levels, especially in
      patients with RA of <=5 years' duration. This strongly suggests a role of B10
      cells in RA initiation.

PMID- 24729480
TI  - Fluorographites (CF(x))n exhibit improved heterogeneous electron-transfer rates
      with increasing level of fluorination: towards the sensing of biomolecules.
AB  - Halogenated sp(2) materials are of high interest owing to their important
      electronic and electrochemical properties. Although methods for graphite and
      graphene fluorination have been extensively researched, the fundamental
      electrochemical properties of fluorinated graphite are not well established. In
      this paper, the electrochemistry of three fluorographite materials of different
      carbon-to-fluorine ratio were studied: (CF(0.33))n, (CF(0.47))n, and (CF(0.75))n.
      Our findings reveal that the carbon-to-fluorine ratio of fluorographite will
      impact the electrochemical performance. Faster heterogeneous electron-transfer
      (HET) rates and lowered oxidation potentials for ascorbic acid and uric acid are
      progressively obtained with increasing fluorine content. The fluorographite
      (CF(0.75))n was in fact found to exhibit the most improved electrochemical
      performances with the fastest HET rates and significantly lowered overpotentials
      in the oxidation of ascorbic acid. Analytical parameters such as sensitivity and
      linearity were subsequently investigated by applying the fluorographite
      (CF(0.75))n in the analysis of ascorbic acid and uric acid, which can be
      simultaneously detected. We determined good linear responses towards the
      detection of both ascorbic and uric acid. Fluorographites outperform graphites in
      sensing applications, which will have a profound impact on applications of
      fluorographites and fluorographene in sensing and biosensing.

PMID- 24729481
TI  - Docosahexaenoic acid attenuates breast cancer cell metabolism and the Warburg
      phenotype by targeting bioenergetic function.
AB  - Docosahexaenoic acid (DHA; C22:6n-3) depresses mammary carcinoma proliferation
      and growth in cell culture and in animal models. The current study explored the
      role of interrupting bioenergetic pathways in BT-474 and MDA-MB-231 breast cancer
      cell lines representing respiratory and glycolytic phenotypes, respectively and
      comparing the impacts of DHA with a non-transformed cell line, MCF-10A. Metabolic
      investigation revealed that DHA supplementation significantly diminished the
      bioenergetic profile of the malignant cell lines in a dose-dependent manner. DHA
      enrichment also resulted in decreases in hypoxia-inducible factor (HIF-1alpha)
      total protein level and transcriptional activity in the malignant cell lines but
      not in the non-transformed cell line. Downstream targets of HIF-1alpha, including
      glucose transporter 1 (GLUT 1) and lactate dehydrogenase (LDH), were decreased by
      DHA treatment in the BT-474 cell line, as well as decreases in LDH protein level
      in the MDA-MB-231 cell line. Glucose uptake, total glucose oxidation, glycolytic
      metabolism, and lactate production were significantly decreased in response to
      DHA supplementation; thereby enhancing metabolic injury and decreasing oxidative
      metabolism. The DHA-induced metabolic changes led to a marked decrease of
      intracellular ATP levels by 50% in both cancer cell lines, which mediated
      phosphorylation of metabolic stress marker, AMPK, at Thr172. These findings show
      that DHA contributes to impaired cancer cell growth and survival by altering
      cancer cell metabolism, increasing metabolic stress and altering HIF-1alpha
      associated metabolism, while not affecting non-transformed MCF-10A cells. This
      study provides rationale for enhancement of current cancer prevention models and
      current therapies by combining them with dietary sources, like DHA.

PMID- 24729482
TI  - Highly active electrocatalysis of the hydrogen evolution reaction by cobalt
      phosphide nanoparticles.
AB  - Nanoparticles of cobalt phosphide, CoP, have been prepared and evaluated as
      electrocatalysts for the hydrogen evolution reaction (HER) under strongly acidic
      conditions (0.50 M H2SO4, pH 0.3). Uniform, multi-faceted CoP nanoparticles were
      synthesized by reacting Co nanoparticles with trioctylphosphine. Electrodes
      comprised of CoP nanoparticles on a Ti support (2 mg cm(-2) mass loading)
      produced a cathodic current density of 20 mA cm(-2) at an overpotential of -85
      mV. The CoP/Ti electrodes were stable over 24 h of sustained hydrogen production
      in 0.50 M H2SO4. The activity was essentially unchanged after 400 cyclic
      voltammetric sweeps, suggesting long-term viability under operating conditions.
      CoP is therefore amongst the most active, acid-stable, earth-abundant HER
      electrocatalysts reported to date.

PMID- 24729479
TI  - Intestinal tumor suppression in ApcMin/+ mice by prostaglandin D2 receptor PTGDR.
AB  - Our earlier work showed that knockout of hematopoietic prostaglandin D synthase
      (HPGDS, an enzyme that produces prostaglandin D2) caused more adenomas in
      Apc(Min/+) mice. Conversely, highly expressed transgenic HPGDS allowed fewer
      tumors. Prostaglandin D2 (PGD2) binds to the prostaglandin D2 receptor known as
      PTGDR (or DP1). PGD2 metabolites bind to peroxisome proliferator-activated
      receptor gamma (PPARG). We hypothesized that Ptgdr or Pparg knockouts may raise
      numbers of tumors, if these receptors take part in tumor suppression by PGD2. To
      assess, we produced Apc(Min/+) mice with and without Ptgdr knockouts (147 mice).
      In separate experiments, we produced Apc(Min/+) mice expressing transgenic
      lipocalin-type prostaglandin D synthase (PTGDS), with and without heterozygous
      Pparg knockouts (104 mice). Homozygous Ptgdr knockouts raised total numbers of
      tumors by 30-40% at 6 and 14 weeks. Colon tumors were not affected. Heterozygous
      Pparg knockouts alone did not affect tumor numbers in Apc(Min/+) mice. As
      mentioned above, our Pparg knockout assessment also included mice with highly
      expressed PTGDS transgenes. Apc(Min/+) mice with transgenic PTGDS had fewer large
      adenomas (63% of control) and lower levels of v-myc avian myelocytomatosis viral
      oncogene homolog (MYC) mRNA in the colon. Heterozygous Pparg knockouts appeared
      to blunt the tumor-suppressing effect of transgenic PTGDS. However, tumor
      suppression by PGD2 was more clearly mediated by receptor PTGDR in our
      experiments. The suppression mechanism did not appear to involve changes in
      microvessel density or slower proliferation of tumor cells. The data support a
      role for PGD2 signals acting through PTGDR in suppression of intestinal tumors.

PMID- 24729483
TI  - The use of antidepressants in patients with advanced cancer--results from an
      international multicentre study.
AB  - OBJECTIVES: Depression is common in patients with advanced cancer; however, it is
      not often recognized and therefore not treated. The aims of this study were to
      examine the prevalence of the use of antidepressants (ADs) in an international
      cross-sectional study sample and to identify sociodemographic and medical
      variables associated with their use. METHODS: The study was conducted in patients
      with advanced cancer from 17 centres across eight countries. Healthcare
      professionals registered patient and disease-related characteristics. A
      dichotomous score (no/yes) was used to assess the use of ADs other than as
      adjuvant for pain. Self-report questionnaires from patients were used for the
      assessment of functioning and symptom intensity. RESULTS: Of 1051 patient records
      with complete data on ADs, 1048 were included (M:540/F:508, mean age 62 years,
      standard deviation [SD] 12). The majority were inpatients, and 85% had metastatic
      disease. The prevalence of AD use was 14%. Multivariate logistic regression
      analyses showed that younger age (odds ratio [OR] 2.46; confidence interval [CI]
      1.32-4.55), female gender (OR 1.59; CI 1.09-2.33), current medication for pain
      (OR 2.68; CI 1.65-4.33) and presence of three or more co-morbidities (OR 4.74; CI
      2.27-9.91) were associated with AD use for reasons other than pain. Disease
      related variables (diagnoses, stage, Karnofsky Performance Status and survival)
      were not associated with the use of ADs. CONCLUSIONS: Female gender, younger age,
      analgesic use and multiple co-morbidities were associated with the use of ADs.
      However, information is still limited on which variables guide physicians in
      prescribing AD medication. Further longitudinal studies including details on
      psychiatric and medication history are needed to improve the identification of
      patients in need of ADs.

PMID- 24729484
TI  - The homozygous VHL(D126N) missense mutation is associated with dramatically
      elevated erythropoietin levels, consequent polycythemia, and early onset severe
      pulmonary hypertension.
AB  - von Hippel-Lindau (VHL) protein is the principal negative regulator of hypoxia
      sensing mediated by transcription factors. Mutations in exon 3 of the VHL gene
      lead to Chuvash (VHL(R200W)) and Croatian (VHL(H191D)) polycythemias. Here, we
      describe an infant of Bangladesh ethnicity with a novel homozygous VHL(D126N)
      mutation with congenital polycythemia and dramatically elevated erythropoietin
      (EPO) levels, who developed severe fatal pulmonary hypertension. In contrast to
      Chuvash polycythemia, erythroid progenitors (BFU-Es) did not reveal a marked EPO
      hypersensitivity. Further, NF-E2 and RUNX1 transcripts that correlate with BFU-Es
      EPO hypersensitivity in polycythemic mutations were not elevated.

PMID- 24729485
TI  - Mg2+-dependent modulation of BKCa channels by genistein in rat arteriolar smooth
      muscle cells.
AB  - Genistein, a protein tyrosine kinase (PTK) inhibitor, regulates ion channel
      activities. However, the mechanism of action of genistein on large-conductance
      calcium-activated potassium (BK(Ca)) channels is unclear. This study aimed to
      investigate whether the mechanism of Mg(2+)-dependent modulation of BK(Ca)
      channel activity in vascular smooth muscle cells involved inhibition of
      phosphorylation by genistein or direct interaction between genistein and BK(Ca)
      channels. The whole-cell and inside-out patch-clamp techniques were used to
      measure BK(Ca) currents and the effects of genistein on BK(Ca) channel activities
      in rat mesenteric arteriolar smooth muscle cells. We found that the effects of
      genistein on BK(Ca) currents were Mg(2+)-dependent. Genistein (50 MUM) inhibited
      BK(Ca) currents if the intracellular free magnesium concentration ([Mg(2+)]i) was
      2 MUM or 20 MUM, but amplified BK(Ca) currents if [Mg(2+)]i was 200 MUM or 2000
      MUM. The inhibitory effect of genistein on BK(Ca) currents was reversed by the
      protein tyrosine phosphatase inhibitor sodium orthovanadate (0.5 mM). Daidzein
      (50 MUM), an inactive analogue of genistein, also amplified BK(Ca) currents, and
      its amplification was insensitive to orthovanadate. Another PTK inhibitor,
      tyrphostin 23 (50 MUM), reduced the open probability of BK(Ca) channels. This
      inhibitory effect was weaker at 200 MUM [Mg(2+)]i than at 2 MUM [Mg(2+) ]i, and
      was countered by orthovanadate. Our results suggest that genistein amplifies
      BK(Ca) currents at a high [Mg(2+)]i, but inhibits BK(Ca) currents at a low
      [Mg(2+)]i. The mechanism of this biphasic effects involves PTK-independent
      amplification and [Mg(2+)]i -PTK-dependent inhibition.

PMID- 24729486
TI  - Sonication-induced formation of size-controlled self-assemblies of amphiphilic
      Janus-type polymers as optical tumor-imaging agents.
AB  - In this study, amphiphilic Janus-type polymers were synthesized via ring-opening
      metathesis polymerization (ROMP), multiple vicinal diol formation, and grafting
      of poly(ethylene glycol) monomethyl ether (mPEG). These amphiphilic polymers
      formed self-assemblies, which were a mixture of micelles and multimicellar
      aggregates, in water. By choosing suitable Janus-type polymers and irradiating an
      aqueous solution of polymers using a sonicator, either small micelles or large
      multimicellar aggregates were obtained selectively. Hydrophobic substituents
      controlled the aggregation-disaggregation behavior, leading to the formation of
      metastable self-assemblies by sonication. The formation of self-assemblies with a
      uniform size was affected by ultrasonic frequency, rather than power. In vivo
      optical tumor imaging revealed that the large-size multimicellar aggregates
      persisting for a long time in blood circulation slowly accumulated in tumor
      tissues. In contrast, the tumor site was rapidly, clearly visualized using the
      small-size micelles. 

PMID- 24729487
TI  - Partitioning of perfluorooctanesulfonate and perfluorohexanesulfonate in the
      aquatic environment after an accidental release of aqueous film forming foam at
      Schiphol Amsterdam Airport.
AB  - In summer 2008, an accidental release of aqueous film forming foam (AFFF) took
      place at Schiphol Amsterdam Airport (The Netherlands). After the release, water,
      fish, and sediment samples were collected and analyzed for perfluoroalkyl
      sulfonates (PFSAs). In situ perfluorooctane sulfonate (PFOS) sediment-water
      distribution factor (KD ) values, bioaccumulation factor (BAF) values, and biota
      sediment accumulation factor (BSAF) values showed a remarkable agreement among
      reference and impacted sites, 10 wk after the incident as well as after 3 yr.

PMID- 24729488
TI  - Editorial: regulatory B cells: are we really ready to manipulate them for the
      benefit of patients with autoimmune diseases?

PMID- 24729489
TI  - The influence of sampling design on tree-ring-based quantification of forest
      growth.
AB  - Tree-rings offer one of the few possibilities to empirically quantify and
      reconstruct forest growth dynamics over years to millennia. Contemporaneously
      with the growing scientific community employing tree-ring parameters, recent
      research has suggested that commonly applied sampling designs (i.e. how and which
      trees are selected for dendrochronological sampling) may introduce considerable
      biases in quantifications of forest responses to environmental change. To date, a
      systematic assessment of the consequences of sampling design on dendroecological
      and-climatological conclusions has not yet been performed. Here, we investigate
      potential biases by sampling a large population of trees and replicating diverse
      sampling designs. This is achieved by retroactively subsetting the population and
      specifically testing for biases emerging for climate reconstruction, growth
      response to climate variability, long-term growth trends, and quantification of
      forest productivity. We find that commonly applied sampling designs can impart
      systematic biases of varying magnitude to any type of tree-ring-based
      investigations, independent of the total number of samples considered.
      Quantifications of forest growth and productivity are particularly susceptible to
      biases, whereas growth responses to short-term climate variability are less
      affected by the choice of sampling design. The world's most frequently applied
      sampling design, focusing on dominant trees only, can bias absolute growth rates
      by up to 459% and trends in excess of 200%. Our findings challenge paradigms,
      where a subset of samples is typically considered to be representative for the
      entire population. The only two sampling strategies meeting the requirements for
      all types of investigations are the (i) sampling of all individuals within a
      fixed area; and (ii) fully randomized selection of trees. This result advertises
      the consistent implementation of a widely applicable sampling design to
      simultaneously reduce uncertainties in tree-ring-based quantifications of forest
      growth and increase the comparability of datasets beyond individual studies,
      investigators, laboratories, and geographical boundaries.

PMID- 24729490
TI  - Nonlinear dimensionality reduction for visualizing toxicity data: distance-based
      versus topology-based approaches.
AB  - Over the years, a number of dimensionality reduction techniques have been
      proposed and used in chemoinformatics to perform nonlinear mappings. In this
      study, four representatives of nonlinear dimensionality reduction methods related
      to two different families were analyzed: distance-based approaches (Isomap and
      Diffusion Maps) and topology-based approaches (Generative Topographic Mapping
      (GTM) and Laplacian Eigenmaps). The considered methods were applied for the
      visualization of three toxicity datasets by using four sets of descriptors. Two
      methods, GTM and Diffusion Maps, were identified as the best approaches, which
      thus made it impossible to prioritize a single family of the considered
      dimensionality reduction methods. The intrinsic dimensionality assessment of data
      was performed by using the Maximum Likelihood Estimation. It was observed that
      descriptor sets with a higher intrinsic dimensionality contributed maps of lower
      quality. A new statistical coefficient, which combines two previously known ones,
      was proposed to automatically rank the maps. Instead of relying on one of the
      best methods, we propose to automatically generate maps with different parameter
      values for different descriptor sets. By following this procedure, the maps with
      the highest values of the introduced statistical coefficient can be automatically
      selected and used as a starting point for visual inspection by the user. 

PMID- 24729491
TI  - Time-to-detection in culture predicts risk of Mycobacterium tuberculosis
      transmission: a cohort study.
AB  - BACKGROUND: Contact screening is an essential component of all tuberculosis
      control strategies. We hypothesize that time-to-detection (TTD) in liquid culture
      of spontaneously produced sputum samples may help identify index cases at high
      risk of transmission. METHODS: We studied retrospectively a cohort of patients
      with pulmonary tuberculosis in Birmingham, United Kingdom (January 2010-December
      2012). We studied the correlation of TTD with the risk of transmission of
      infection from index cases to contacts and compared this with sputum microscopy.
      Chest radiographs (CXRs) were graded from 0 to 6 (0, no radiographic evidence of
      disease; 5, bilateral cavitation; and 6, miliary disease). RESULTS: Of the 184
      cases of pulmonary tuberculosis reported during the study period, 111 were
      included in the final study, and these generated 825 contacts. A transmission
      event (new latent or active tuberculosis) was identified in 165 contacts
      (transmission rate 0.20). Short TTD (<9 days) was associated with an increased
      risk of transmission (odds ratio, 2.56; P < .001), and this relationship
      persisted after adjusting for potential confounders. A 1-point increase in CXR
      grade correlated with a 3.2-day decrease in TTD (P < .001), and this correlation
      persisted after adjustment for potential confounders. CONCLUSIONS: TTD < 9 days
      identifies patients at high risk of transmitting tuberculosis and is superior to
      sputum smear. CXR grade at diagnosis predicts patients with short TTD. Our
      findings have the potential to guide the organization and prioritization of
      contact investigations in similar settings.

PMID- 24729492
TI  - Lipid levels and changes in body fat distribution in treatment-naive, HIV-1
      Infected adults treated with rilpivirine or Efavirenz for 96 weeks in the ECHO
      and THRIVE trials.
AB  - BACKGROUND: Pooled ECHO/THRIVE lipid and body fat data are presented from the
      ECHO (Efficacy Comparison in Treatment-Naive, HIV-Infected Subjects of TMC278 and
      Efavirenz) and THRIVE (TMC278 Against HIV, in a Once-Daily Regimen Versus
      Efavirenz) trials. METHODS: We assessed the 96-week effects on lipids, adverse
      events (AEs), and body fat distribution (dual-energy x-ray absorptiometry) of
      rilpivirine (RPV) and EFV plus 2 nucleoside/nucleotide reverse transcriptase
      inhibitors (N[t]RTIs) in treatment-naive adults infected with human
      immunodeficiency virus type 1 (HIV-1). RESULTS: Rilpivirine produced minimal
      changes in total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-C),
      high-density lipoprotein cholesterol (HDL-C), and triglycerides. Compared with
      RPV, EFV significantly (P < .001) increased lipid levels. Decreases in the TC/HDL
      C ratio were similar with RPV and EFV. Background N[t]RTI affected RPV-induced
      lipid changes; all levels increased with zidovudine/lamivudine (3TC) and
      abacavir/3TC (except triglycerides, which were unchanged). With
      emtricitabine/tenofovir, levels of HDL-C were increased, TC and LDL-C were
      unchanged, and triglycerides were decreased. With EFV, lipid levels increased in
      each N[t]RTI subgroup (except triglycerides were unchanged with abacavir/3TC).
      Fewer (P < .001) RPV-treated patients than EFV-treated patients had TC, LDL-C,
      and triglyceride levels above National Cholesterol Education Program cutoffs.
      More RPV- than EFV-treated patients had HDL-C values below these cutoffs (P =
      .02). Dyslipidemia AEs were less common with RPV than with EFV. Similar
      proportions of patients had a >=10% decrease in limb fat (16% with RPV and 17%
      with EFV). Limb fat was significantly (P < .001) increased to a similar extent
      (by 12% with RPV and 11% with EFV). At week 96, patients receiving zidovudine/3TC
      had lost limb fat, and those receiving emtricitabine/tenofovir had gained it.
      CONCLUSIONS: Over the course of 96 weeks, RPV-based therapy was associated with
      lower increases in lipid parameters and fewer dyslipidemia AEs than EFV-based
      treatment. Body fat distribution changes were similar between treatments. The
      N[t]RTI regimen affected lipid and body fat distribution changes.

PMID- 24729493
TI  - Improving outcomes for multidrug-resistant tuberculosis: aggressive regimens
      prevent treatment failure and death.
AB  - BACKGROUND: Evidence is sparse regarding the optimal construction of regimens to
      treat multidrug-resistant (MDR) tuberculosis disease due to strains of
      Mycobacterium tuberculosis resistant to at least both isoniazid and rifampin.
      Given the low potency of many second-line antituberculous drugs, we hypothesized
      that an aggressive regimen of at least 5 likely effective drugs during the
      intensive phase, including a fluoroquinolone and a parenteral agent, would be
      associated with a reduced risk of death or treatment failure. METHODS: We
      conducted a retrospective cohort study of patients initiating MDR tuberculosis
      treatment between 2000 and 2004 in Tomsk, Russian Federation. We used a
      multivariate Cox proportional hazards model to assess whether monthly exposure to
      an aggressive regimen was associated with the risk of death or treatment failure.
      RESULTS: Six hundred fourteen individuals with confirmed MDR tuberculosis were
      eligible for analysis. On multivariable analysis that adjusted for extensively
      drug-resistant (XDR) tuberculosis-MDR tuberculosis isolates resistant to
      fluoroquinolones and parenteral agents-we found that monthly exposure to an
      aggressive regimen was significantly associated with a lower risk of death or
      treatment failure (hazard ratio, 0.52 [95% confidence interval, .29-.94]; P =
      .030). CONCLUSIONS: Receipt of an aggressive treatment regimen was a robust
      predictor of decreased risk of death or failure during MDR tuberculosis
      treatment. These findings further support the use of this regimen definition as
      the benchmark for the standard of care of MDR tuberculosis patients and should be
      used as the basis for evaluating novel therapies.

PMID- 24729494
TI  - Mycoplasma genitalium testing pattern and macrolide resistance: a Danish
      nationwide retrospective survey.
AB  - BACKGROUND: Mycoplasma genitalium is a common cause of nongonococcal urethritis
      (NGU) and cervicitis. The aim of the study was to analyze the M. genitalium
      testing pattern and distribution of positive results according to sex and age in
      a 5-year period where all diagnostic M. genitalium testing in Denmark was
      centralized at the Statens Serum Institut. A secondary aim was to estimate the
      occurrence of macrolide resistance in a 3-year period. METHODS: The study was
      performed as a nationwide retrospective survey of specimens submitted from
      general practice, private specialists, and hospitals to Statens Serum Institut
      for detection of M. genitalium by polymerase chain reaction between 1 January
      2006 and 31 December 2010. Macrolide resistance screening was introduced December
      2007. RESULTS: A total of 31 600 specimens from 28 958 patients were tested for
      M. genitalium, with an increasing trend from 3858 per year in 2006 to 7361 in
      2010. The majority (54%) of the patients were tested in general practice. For
      both sexes, the positive rate increased significantly, from 2.4% to 3.8% for
      women and from 7.9% to 10.3% for men (P < .0005). Macrolide resistance was
      detected in 38% (385/1008) of the M. genitalium-positive patients, and the
      highest rate was found in patients tested at sexually transmitted disease clinics
      (43%). CONCLUSIONS: Testing for M. genitalium has become important for clinicians
      treating sexually transmitted infections. In this nationwide survey, macrolide
      resistance was found in almost 40% of the specimens, raising concern about single
      dose azithromycin treatment of NGU, and emphasizing that NGU treatment should be
      guided by etiologic diagnosis.

PMID- 24729495
TI  - Reply to Hong et al.

PMID- 24729496
TI  - Fluoroquinolone use is a risk factor for methicillin-resistant Staphylococcus
      aureus acquisition in long-term care facilities: a nested case-case-control
      study.
AB  - BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) nasal colonization
      is a well-established risk factor for subsequent infection and a key event in
      interindividual transmission. Some studies have showed an association between
      fluoroquinolones and MRSA colonization or infection. The present study was
      performed to identify specific risk factors for MRSA acquisition in long-term
      care facilities (LTCFs). METHODS: A prospective cohort of patients naive for S.
      aureus colonization was established and followed (January 2008 through October
      2010) in 4 French LTCFs. Nasal colonization status and potential risk factors
      were assessed weekly for 13 weeks after inclusion. Variables associated with S.
      aureus acquisition were identified in a nested-matched case-case-control study
      using conditional logistic regression models. Cases were patients who acquired
      MRSA (or methicillin-sensitive S. aureus [MSSA]). Patients whose nasal swab
      samples were always negative served as controls. Matching criteria were center,
      date of first nasal swab sample, and exposure time. RESULTS: Among 451 included
      patients, 76 MRSA cases were matched to 207 controls and 112 MSSA cases to 208
      controls. Multivariable analysis retained fluoroquinolones (odds ratio, 2.17; 95%
      confidence interval, 1.01-4.67), male sex (2.09; 1.10-3.98), and more intensive
      care at admission (3.24; 1.74-6.04) as significantly associated with MRSA
      acquisition, and body-washing assistance (2.85; 1.27-6.42) and use of a urination
      device (1.79; 1.01-3.18) as significantly associated with MSSA acquisition.
      CONCLUSIONS: Our results suggest that fluoroquinolones are a risk factor for MRSA
      acquisition. Control measures to limit MRSA spread in LTCFs should also be based
      on optimization of fluoroquinolone use.

PMID- 24729497
TI  - Reply to Di Paolo et al.

PMID- 24729498
TI  - Lower respiratory tract virus findings in mechanically ventilated patients with
      severe community-acquired pneumonia.
AB  - BACKGROUND: The role of viral infections in the etiology of severe community
      acquired pneumonia (SCAP) was prospectively evaluated from 2008 to 2012 at a
      university-level intensive care unit. METHODS: Clinical data and microbiological
      tests were assessed: blood cultures, urine pneumococcal and legionella antigens,
      Mycoplasma pneumoniae and Chlamydia pneumoniae antibodies from paired serums, and
      respiratory virus detection by multiplex, real-time polymerase chain reaction
      (PCR) from nasopharyngeal swabs and lower tracheal specimens via intubation tube.
      RESULTS: Of 49 mechanically ventilated SCAP patients (21 men and 28 women; median
      age, 54 years), the etiology was identified in 45 cases (92%). There were 21 pure
      bacterial infections (43%), 5 probably pure viral infections (10%), and 19 mixed
      bacterial-viral infections (39%), resulting in viral etiology in 24 patients
      (49%). Of 26 viruses, 21 (81%) were detected from bronchial specimens and 5 (19%)
      from nasopharyngeal swabs. Rhinovirus (15 cases, 58%) and adenovirus (4 cases,
      15%) were the most common viral findings. The bacterial-viral etiology group had
      the highest peak C-reactive protein levels (median, 356 [25th-75th percentiles,
      294-416], P = .05), whereas patients with probably viral etiology had the lowest
      peak procalcitonin levels (1.7 [25th-75th percentiles, 1.6-1.7]). The clinical
      characteristics of pure bacterial and mixed bacterial-viral etiologies were
      comparable. Hospital stay was longest among the bacterial group (17 vs 14 days; P
      = .02). CONCLUSIONS: Viral findings were demonstrated in almost half of the SCAP
      patients. Clinical characteristics were similar between the pure bacterial and
      mixed bacterial-viral infections groups. The frequency of viral detection depends
      on the availability of PCR techniques and lower respiratory specimens.

PMID- 24729499
TI  - Different recommendations for daptomycin dosing over time in patients with severe
      infections.

PMID- 24729500
TI  - Is the sensitivity of the QuantiFERON-TB gold in-tube test lower than that of T
      SPOT.TB in patients with miliary tuberculosis?

PMID- 24729501
TI  - Human T-cell lymphotropic virus type 1 exposures following blood-borne virus
      incidents in central Australia, 2002-2012.
AB  - We retrospectively audited hospital occupational exposure events over a 10-year
      period, in a human T-cell lymphotropic virus type 1 (HTLV-1)-endemic area of
      Central Australia, and report on 53 individuals exposed to HTLV-1 with no
      transmissions documented (95% confidence interval, 0%-1.5%). This has important
      implications for the management of exposures including the role of postexposure
      prophylaxis. 

PMID- 24729502
TI  - Outbreak of Serratia marcescens bloodstream infections in patients receiving
      parenteral nutrition prepared by a compounding pharmacy.
AB  - BACKGROUND: Compounding pharmacies often prepare parenteral nutrition (PN) and
      must adhere to rigorous standards to avoid contamination of the sterile
      preparation. In March 2011, Serratia marcescens bloodstream infections (BSIs)
      were identified in 5 patients receiving PN from a single compounding pharmacy. An
      investigation was conducted to identify potential sources of contamination and
      prevent further infections. METHODS: Cases were defined as S. marcescens BSIs in
      patients receiving PN from the pharmacy between January and March 2011. We
      reviewed case patients' clinical records, evaluated pharmacy compounding
      practices, and obtained epidemiologically directed environmental cultures.
      Molecular relatedness of available Serratia isolates was determined by pulsed
      field gel electrophoresis (PFGE). RESULTS: Nineteen case patients were
      identified; 9 died. The attack rate for patients receiving PN in March was 35%.
      No case patients were younger than 18 years. In October 2010, the pharmacy began
      compounding and filter-sterilizing amino acid solution for adult PN using
      nonsterile amino acids due to a national manufacturer shortage. Review of this
      process identified breaches in mixing, filtration, and sterility testing
      practices. S. marcescens was identified from a pharmacy water faucet, mixing
      container, and opened amino acid powder. These isolates were indistinguishable
      from the outbreak strain by PFGE. CONCLUSIONS: Compounding of nonsterile amino
      acid components of PN was initiated due to a manufacturer shortage. Failure to
      follow recommended compounding standards contributed to an outbreak of S.
      marcescens BSIs. Improved adherence to sterile compounding standards, critical
      examination of standards for sterile compounding from nonsterile ingredients, and
      more rigorous oversight of compounding pharmacies is needed to prevent future
      outbreaks.

PMID- 24729503
TI  - Rates and risk factors for recurrent pneumonia in patients hospitalized with
      community-acquired pneumonia: population-based prospective cohort study with 5
      years of follow-up.
AB  - BACKGROUND: The rates and risk factors for developing recurrent pneumonia
      following hospitalization with community-acquired pneumonia (CAP) are poorly
      understood. METHODS: We examined a population-based cohort of patients with CAP
      who survived hospital admission and who were free of pneumonia for at least 3
      months. We collected clinical, functional, and medication-related information and
      pneumonia severity index (PSI). Using linked databases we followed patients for 5
      years and captured any clinical episode of pneumonia 90 days or more post
      discharge. We used Cox proportional hazards models (adjusted for age, sex, PSI,
      functional status, medications) to determine rates and independent correlates of
      recurrent pneumonia. RESULTS: The final cohort included 2709 inpatients; 43% were
      75 years or older, 34% were not fully independent, and 56% had severe pneumonia.
      Over 5 years of follow-up, 245 (9%; 95% confidence interval [CI], 8%-10%)
      patients developed recurrent pneumonia, and 156 (64%) of these episodes required
      hospitalization. Rate of recurrence was 3.0/100 person-years and median time to
      recurrence was 317 days (interquartile range, 177-569); 32 (13%) patients had 2
      or more recurrences. In multivariable analyses only age >75 years (adjusted P =
      .047) and less than fully independent functional status (12% recurrence rate with
      impaired functional status vs 7% for fully independent; adjusted hazard ratio,
      1.7; 95% CI, 1.3-2.2; P < .001) were significantly associated with recurrent
      pneumonia. CONCLUSIONS: One of 11 patients who survived CAP hospitalization had
      recurrent pneumonia over 5 years and those with impaired functional status were
      at particularly high risk. Recurrent pneumonia is common and more attention to
      preventive strategies at discharge and closer follow-up over the long-term seem
      warranted.

PMID- 24729504
TI  - What is the real role of respiratory viruses in severe community-acquired
      pneumonia?

PMID- 24729505
TI  - Diagnostic and resistance testing for Mycoplasma genitalium: what will it take?

PMID- 24729506
TI  - Xpert MTB/RIF assay shortens airborne isolation for hospitalized patients with
      presumptive tuberculosis in the United States.
AB  - BACKGROUND: In the United States, individuals with presumptive pulmonary
      tuberculosis are placed in airborne infection isolation (AII) and assessed by
      smear microscopy on 3 respiratory specimens collected 8-24 hours apart. Xpert
      MTB/RIF assay (Xpert) on 1, 2, or 3 specimens may be more efficient for
      determining AII discontinuation. METHODS: This single-center, observational
      cohort study of inpatients with presumptive pulmonary tuberculosis enrolled
      adults with 1 or more sputum specimens submitted for smear microscopy. Smear
      microscopy and Xpert were performed on each sputum specimen. Clinicians were
      blinded to Xpert results. The primary endpoint was AII duration. Secondary
      endpoints were laboratory processing time, strategy-based tuberculosis detection,
      and sensitivity and specificity. RESULTS: Among 207 subjects, the median AII
      duration was 68.0 hours (interquartile range [IQR], 47.1-97.5) for smear
      microscopy compared with 20.8 hours (IQR, 16.8-32.0) for the 1-specimen Xpert,
      41.2 hours (IQR, 26.6-54.8) for the 2-specimen Xpert, and 54.0 hours (IQR, 43.3
      80.0) for the 3-specimen Xpert strategies (P <= .004). Median laboratory
      processing time for smear microscopy was 2.5 times as long as Xpert (P < .001).
      The 2- and 3-specimen Xpert and smear microscopy strategies captured all 6
      tuberculosis cases. The 1-specimen Xpert strategy missed 1 case. No difference
      was observed between smear microscopy and Xpert in sensitivity or specificity for
      detection of Mycobacterium tuberculosis. CONCLUSIONS: Xpert-based strategies
      significantly reduced AII duration compared with the smear-based strategy. The 2
      specimen Xpert strategy was most efficient in minimizing AII time while
      identifying all tuberculosis cases among individuals with presumptive
      tuberculosis in this low-burden setting.

PMID- 24729507
TI  - Azithromycin versus doxycycline for the treatment of genital chlamydia infection:
      a meta-analysis of randomized controlled trials.
AB  - BACKGROUND: There has been recent debate questioning the efficacy of azithromycin
      for the treatment of urogenital chlamydia infection. We conducted a meta-analysis
      to compare the efficacy of 1 g azithromycin with 100 mg doxycycline twice daily
      (7 days) for the treatment of urogenital chlamydia infection. METHODS: Medline,
      PubMed, Embase, Cochrane Controlled Trials Register, Cochrane reviews, and
      Cumulative Index to Nursing and Allied Health Literature were searched until 31
      December 2013. Randomized controlled trials comparing azithromycin with
      doxycycline for the treatment of genital chlamydia with evaluation of
      microbiological cure within 3 months of treatment were included. Sex, diagnostic
      test, follow-up time, attrition, patient symptomatic status, and microbiological
      cure were extracted. The primary outcome was the difference in efficacy at final
      follow-up. Study bias was quantitatively and qualitatively summarized. RESULTS:
      Twenty-three studies were included evaluating 1147 and 912 patients for
      azithromycin and doxycycline, respectively. We found a pooled efficacy difference
      in favor of doxycycline of 1.5% (95% confidence interval [CI], -.1% to 3.1%; I(2)
      = 1.9%; P = .435; random effects) to 2.6% (95% CI, .5%-4.7%; fixed effects).
      Subgroup analyses showed that the fixed effects pooled efficacy difference for
      symptomatic men was 7.4% (95% CI, 2.0%-12.9%), and the random effects was 5.5%
      (95% CI, -1.4% to 12.4%). CONCLUSIONS: There may be a small increased efficacy of
      up to 3% for doxycycline compared with azithromycin for the treatment of
      urogenital chlamydia and about 7% increased efficacy for doxycycline for the
      treatment of symptomatic urethral infection in men. However, the quality of the
      evidence varies considerably, with few double-blind placebo-controlled trials
      conducted. Given increasing concern about potential azithromycin failure, further
      well-designed and statistically powered double-blind, placebo-controlled trials
      are needed.

PMID- 24729509
TI  - Elucidation of the structure of organic solutions in solvent extraction by
      combining molecular dynamics and X-ray scattering.
AB  - Knowledge of the supramolecular structure of the organic phase containing
      amphiphilic ligand molecules is mandatory for full comprehension of ionic
      separation during solvent extraction. Existing structural models are based on
      simple geometric aggregates, but no consensus exists on the interaction
      potentials. Herein, we show that molecular dynamics crossed with scattering
      techniques offers key insight into the complex fluid involving weak interactions
      without any long-range ordering. Two systems containing mono- or diamide
      extractants in heptane and contacted with an aqueous phase were selected as
      examples to demonstrate the advantages of coupling the two approaches for
      furthering fundamental studies on solvent extraction. 

PMID- 24729508
TI  - Organization of the Escherichia coli aerobic enzyme complexes of oxidative
      phosphorylation in dynamic domains within the cytoplasmic membrane.
AB  - The Escherichia coli cytoplasmic membrane contains the enzyme complexes of
      oxidative phosphorylation (OXPHOS). Not much is known about their supramolecular
      organization and their dynamics within the membrane in this model organism. In
      mitochondria and other bacteria, it was demonstrated by nondenaturing
      electrophoretic methods and electron microscopy that the OXPHOS complexes are
      organized in so-called supercomplexes, stable assemblies with a defined number of
      the individual enzyme complexes. To investigate the organization of the E. coli
      enzyme complexes of aerobic OXPHOS in vivo, we established fluorescent protein
      fusions of the NADH:ubiquinone oxidoreductase, the succinate:ubiquinone
      oxidoreductase, the cytochrome bd-I, and the cytochrome bo3 terminal oxidases,
      and the FoF1 ATP-synthase. The fusions were integrated in the chromosome to
      prevent artifacts caused by protein overproduction. Biochemical analysis revealed
      that all modified complexes were fully assembled, active, and stable. The
      distribution of the OXPHOS complexes in living cells was determined using total
      internal reflection fluorescence microscopy. The dynamics within the membrane
      were detected by fluorescence recovery after photobleaching. All aerobic OXPHOS
      complexes showed an uneven distribution in large mobile patches within the E.
      coli cytoplasmic membrane. It is discussed whether the individual OXPHOS
      complexes are organized as clustered individual complexes, here called
      "segrazones."

PMID- 24729510
TI  - Zinc-catalyzed [4+3] cycloaddition with concomitant furan annulation: formation
      of cyclohepta[b]furans.
AB  - A convenient zinc-promoted [4+3] cycloaddition of a carbonyl ene-yne with simple
      dienes was first achieved. This reaction provided an efficient strategy to
      prepare various cyclohepta[b]furan rings by cascade cycloadditions. Additionally,
      a multicomponent reaction of dione, alkynal, and diene was also reported, which
      exhibited a novel strategy for selective creations of C-O bonds and C-C bonds.

PMID- 24729511
TI  - Association of a functional RAD52 genetic variant locating in a miRNA binding
      site with risk of HBV-related hepatocellular carcinoma.
AB  - As an important member in homologous recombination repair, RAD52 plays a crucial
      part in maintaining genomic stability and prevent carcinogenesis. Several cancer
      susceptibility RAD52 single nucleotide polymorphisms (SNPs) have been identified
      previously. However, little or nothing has been known about the RAD52 SNPs and
      their functional significance in hepatitis B viruses (HBV)-related hepatocellular
      carcinoma (HCC). Therefore, we investigated the association between five RAD52
      SNPs (rs1051669, rs10774474, rs11571378, rs7963551, and rs6489769) and HBV
      related HCC risk as well as its biological function in vivo. Genotypes were
      determined in two independent case-control sets from two regions of China. Odds
      ratios (ORs) and 95% confidence intervals (CIs) were estimated by logistic
      regression. The allele-specific regulation on RAD52 expression by the functional
      genetic variant was examined with normal liver tissues. We found that only the
      RAD52 rs7963551 SNP was significantly associated with HCC risk, with the odds of
      having the rs7963551 CC genotype in patients was 0.59 (95% CI = 0.45-0.78, P =
      1.5 * 10(-4), HCC cases versus chronic HBV carriers) or 0.65 (95% CI = 0.52-0.81,
      P = 1.1 * 10(-4), HCC cases versus healthy controls) compared with the AA
      genotype. In the genotype-phenotype correlation analyses of 44 human liver tissue
      samples, rs7963551 CC or AC was associated with a statistically significant
      increase of RAD52 mRNA expression, which are consistent to functional relevance
      of allelic regulation of RAD52 expression by rs7963551 SNP and miRNA let-7 in
      cancer cells. Our data demonstrated that RAD52 functional rs7963551 SNP
      contributes to susceptibility to developing HCC.

PMID- 24729512
TI  - Eutectic combinations as a pathway to the formation of substrate-based Au-Ge
      heterodimers and hollowed au nanocrescents with tunable optical properties.
AB  - Pairs of immiscible elements with deep eutectics are used to synthesize periodic
      arrays of heterodimers and hollowed metal nanocrescents. In the devised route,
      substrate-immobilized Au or Ag nanostructures act as heterogeneous nucleation
      sites for Ge adatoms. At elevated temperatures the adatoms collect in sufficient
      quantities to transform each site into a AuGe liquid alloy which, upon cooling,
      phase separates into elemental components sharing a common interface. The so
      formed Au-Ge and Ag-Ge heterodimers exhibit a complex morphology characterized by
      a noble metal nanocrescent which partially encapsulates one end of the Ge domain.
      Through the use of a selective etch the Ge component is removed, leaving behind a
      periodic array of hollow noble metal nanocrescents on the surface of the
      substrate. Optical characterization of both the heterodimers and nanocrescents
      indicates that the presence of Ge gives rise to a relative blue-shift in the
      localized surface plasmon peak, a result that is in stark contrast to the red
      shifts typically observed when plasmonic nanostructures are in contact with a
      dielectric medium. Simulations are used to both rationalize the observed shift
      and show the potential for deriving unexpected behaviors when semishell-like
      noble metal structures are in contact with high permittivity dielectric mediums. 

PMID- 24729513
TI  - The discovery of potent nonstructural protein 5A (NS5A) inhibitors with a unique
      resistance profile-Part 1.
AB  - Nonstructural protein 5A (NS5A) represents a novel target for the treatment of
      hepatitis C virus (HCV). Daclatasvir, recently reported by Bristol-Myers-Squibb,
      is a potent NS5A inhibitor currently under investigation in phase 3 clinical
      trials. While the performance of daclatasvir has been impressive, the emergence
      of resistance could prove problematic and as such, improved analogues are being
      sought. By varying the biphenyl-imidazole unit of daclatasvir, novel inhibitors
      of HCV NS5A were identified with an improved resistance profile against mutant
      strains of the virus while retaining the picomolar potency of daclatasvir. One
      compound in particular, methyl ((S)-1-((S)-2-(4-(4-(6-(2-((S)-1
      ((methoxycarbonyl)-L-valyl)pyrrolidin-2-yl)-1H-imidazol-5-yl)quinoxalin-2
      yl)phenyl)-1H-imidazol-2-yl)pyrrolidin-1-yl)-3-methyl-1-oxobutan-2-yl)carbamate
      (17), exhibited very promising activity and showed good absorption and a long
      predicted human pharmacokinetic half-life. This compound represents a promising
      lead that warrants further evaluation. 

PMID- 24729514
TI  - Surveillance for children at genetic risk for cancer: are we ready?

PMID- 24729515
TI  - Cognitive function, mood, and sleep quality in patients treated with intensity
      modulated radiation therapy for nasopharyngeal cancer: a prospective study.
AB  - OBJECTIVE: The aim of this study was to prospectively evaluate the cognitive
      function, depression, anxiety, and sleep quality in patients with nasopharyngeal
      cancer (NPC) before and after intensity-modulated radiotherapy (IMRT). METHODS:
      Eligible patients with newly diagnosed NPC treated with primary IMRT were
      recruited. A series of neuropsychological tests were performed within 1 week
      before and after IMRT. Cognitive function was measured with the Das-Naglieri
      cognitive assessment system. The Self-rating Anxiety Scale and Self-rating
      Depression Scale were used to assess mood states. Sleep quality was evaluated by
      means of the Pittsburgh Sleep Quality Index. RESULTS: A total of 51 patients were
      enrolled. The overall prevalence of depression, anxiety, and poor sleep quality
      showed a significant increase after RT, compared with their pre-RT levels (39.2%
      vs. 3.9%, p = 0.000; 19.6% vs. 3.9%, p = 0.039; 64.7% vs. 37.3%, p = 0.003,
      respectively). Multiple linear regression analysis revealed that pre-RT
      depression and younger age and pre-RT anxiety and younger age were significant
      predictors of post-RT depression and anxiety, respectively (p < 0.05). Poor sleep
      quality before treatment was also associated with poor sleep after RT (p =
      0.032). However, the cognitive function evaluated by the cognitive assessment
      system from pre-RT was similar to the post-RT results. CONCLUSIONS: Exposure to
      ionizing radiation for the treatment of NPC decreased mood and sleep quality
      following IMRT, especially for patients with depression, anxiety, younger age, or
      poor sleep before treatment. No acute cognitive deficits were found resulting
      from IMRT, but the long-term effects of RT might still warrant concern.

PMID- 24729516
TI  - Calibration differences and the prozone phenomenon in IgG4-related disease:
      comment on the article by Khosroshahi et al.

PMID- 24729517
TI  - Framework of outcome measures recommended for use in the evaluation of childhood
      obesity treatment interventions: the CoOR framework.
AB  - INTRODUCTION: Consensus is lacking in determining appropriate outcome measures
      for assessment of childhood obesity treatments. Inconsistency in the use and
      reporting of such measures impedes comparisons between treatments and limits
      consideration of effectiveness. This study aimed to produce a framework of
      recommended outcome measures: the Childhood obesity treatment evaluation Outcomes
      Review (CoOR) framework. METHODS: A systematic review including two searches was
      conducted to identify (1) existing trial outcome measures and (2) manuscripts
      describing development/evaluation of outcome measures. Outcomes included
      anthropometry, diet, eating behaviours, physical activity, sedentary
      time/behaviour, fitness, physiology, environment, psychological well-being and
      health-related quality of life. Eligible measures were appraised by the internal
      team using a system developed from international guidelines, followed by
      appraisal from national external expert collaborators. RESULTS: A total of 25,486
      papers were identified through both searches. Eligible search 1 trial papers
      cited 417 additional papers linked to outcome measures, of which 56 were
      eligible. A further 297 outcome development/evaluation papers met eligibility
      criteria from search 2. Combined, these described 191 outcome measures. After
      internal and external appraisal, 52 measures across 10 outcomes were recommended
      for inclusion in the CoOR framework. CONCLUSION: Application of the CoOR
      framework will ensure greater consistency in choosing robust outcome measures
      that are appropriate to population characteristics.

PMID- 24729518
TI  - The discovery of potent nonstructural protein 5A (NS5A) inhibitors with a unique
      resistance profile-Part 2.
AB  - In ongoing studies towards novel hepatitis C virus (HCV) therapeutics, inhibitors
      of nonstructural protein 5A (NS5A) were evaluated. Specifically, starting from
      previously reported lead compounds, peripheral substitution patterns of a series
      of biaryl-linked pyrrolidine NS5A replication complex inhibitors were probed and
      structure-activity relationships were elucidated. Using molecular modelling and a
      supercritical fluid chromatographic (SFC) technique, intramolecular H-bonding and
      peripheral functional group topology were evaluated as key determinants of
      activity and membrane permeability. The novel compounds exhibited retained
      potency as compared with the lead compounds, and also showed promising results
      against a panel of resistance viruses. Together, the results of the study take us
      a step closer towards understanding the potency of daclatasvir, a clinical
      candidate upon which the compounds were based, and to designing improved
      analogues as second-generation antiviral agents targeting NS5A. 

PMID- 24729519
TI  - Breast milk leptin and adiponectin in relation to infant body composition up to 2
      years.
AB  - BACKGROUND: Adipokines in breast milk have been associated with infant growth
      trajectories. OBJECTIVE: We aimed to explore the relationship of leptin and
      adiponectin in breast milk with infant weight gain and body composition up to the
      age of 2 years. METHODS: Breast milk samples were collected from exclusively or
      partially breastfeeding mothers at 6 weeks (n = 152) and 4 months (n = 120) post
      partum. Leptin and adiponectin were determined in skim breast milk and related to
      infant growth and fat mass assessed by skin-fold thickness measurements. A total
      of 118 infants were examined at 2 years. RESULTS: The levels of both milk
      adipokines were slightly lower at 4 months compared with 6 weeks post-partum.
      Breast milk leptin was largely unrelated to infant anthropometric measures up to
      2 years. Milk adiponectin tended to be inversely related to early infant
      anthropometry up to 4 months, but beyond was positively associated with weight
      gain and the sum of skin-folds up to 2 years. CONCLUSIONS: Our results suggest
      that higher adiponectin levels in breast milk might be associated with greater
      weight gain and higher fat mass in the offspring up to 2 years.

PMID- 24729520
TI  - Hydrothermal transformation of dried grass into graphitic carbon-based high
      performance electrocatalyst for oxygen reduction reaction.
AB  - In this work, we present a low cost and environmentally benign hydrothermal
      method using dried grass as the sole starting material without any synthetic
      chemicals to directly produce high quality nitrogen-doped carbon
      nanodot/nanosheet aggregates (N-CNAs), achieving a high yield of 25.2%. The
      fabricated N-CNAs possess an N/C atomic ratio of 3.41%, consist of three typed of
      doped N at a ratio of 2.6 (pyridinic):1.7 (pyrrolic):1 (graphitic). The
      experimental results reveal that for oxygen reduction reaction (ORR), the
      performance of N-CNAs, in terms of electrocatalytic activity, stability and
      resistance to crossover effects, is better or comparable to the commercial Pt/C
      electrocatalyst. The theoretical studies further indicate that the doped
      pyridinic-N plays a key role for N-CNAs' excellent four-electron ORR
      electrocatalytic activity. 

PMID- 24729521
TI  - Hybrid organic-inorganic photovoltaics.

PMID- 24729525
TI  - A metallocene molecular complex as visible-light absorber for high-voltage
      organic-inorganic hybrid photovoltaic cells.
AB  - A thin solid-state dye-sensitized photovoltaic cell is fabricated by composing
      organic and inorganic heterojunctions in which the visible-light sensitizers are
      cyclopentadiene derivatives (Cp*) coordinated to a metal oxide, typically TiO2.
      The coordination bonds of the metallocene molecular complex (Ti-Cp*) create a new
      LMCT (ligand-to-metal charge transfer) absorption band and induce a rectified
      charge transfer from the organic ligands to TiO2, leading to photocurrent
      generation. Photovoltaic junctions are completed by coating crystalline organic
      molecules (perylene) as a hole-transport layer on the Cp*-coordinated TiO2
      surface by using the vapor deposition method. The molecular plane of Cp* on the
      TiO2 surfaces seems to help the hole-transport layer to form ordered structures,
      which effectively improve carrier conductivities and minimize interfacial
      resistance. The organic-inorganic hybrid thin-film photocell with metallocene
      molecular complexes is capable of generating high open-circuit voltages exceeding
      1.2 V.

PMID- 24729526
TI  - Mechanisms of electron transport and recombination in ZnO nanostructures for dye
      sensitized solar cells.
AB  - ZnO is an attractive material for applications in dye-sensitized solar cells and
      related devices. This material has excellent electron-transport properties in the
      bulk but its electron diffusion coefficient is much smaller in mesoporous films.
      In this work the electron-transport properties of two different kinds of dye
      sensitized ZnO nanostructures are investigated by small-perturbation
      electrochemical techniques. For nanoparticulate ZnO photoanodes prepared via a
      wet-chemistry technique, the diffusion coefficient is found to reproduce the
      typical behavior predicted by the multiple-trapping and the hopping models, with
      an exponential increase with respect to the applied bias. In contrast, in ZnO
      nanostructured thin films of controlled texture and crystallinity prepared via a
      plasma chemical vapor deposition method, the diffusion coefficient is found to be
      independent of the electrochemical bias. This observation suggests a different
      transport mechanism not controlled by trapping and electron accumulation. In
      spite of the quite different transport features, the recombination kinetics, the
      electron-collection efficiency and the photoconversion efficiency are very
      similar for both kinds of photoanodes, an observation that indicates that surface
      properties rather than electron transport is the main efficiency-determining
      factor in solar cells based on ZnO nanostructured photoanodes. 

PMID- 24729527
TI  - Investigation of dye regeneration kinetics in sensitized solar cells by scanning
      electrochemical microscopy.
AB  - Sensitizers are responsible for the light harvesting and the charge injection in
      dye-sensitized solar cells (DSSCs). A fast dye-regeneration process is necessary
      to obtain highly efficient DSSC devices. Herein, dye-regeneration rates of two
      DSSC device types, that is, the reduction of immediately formed photo-oxidized
      sensitizers (ruthenium complex C106TBA and porphyrin LD14, k(ox)') by iodide ions
      (I(-)) and [Co(bpy)3](2+), and the oxidation of formed photo-reduced sensitizers
      (organic dye P1, k(re)') by triiodide ions (I3(-)) and the disulfide dimer (T2)
      are investigated by scanning electrochemical microscopy (SECM). We provide a
      thorough experimental verification of the feedback mode to compare the kinetics
      for dye-regeneration by using the above mentioned mediators. The charge
      recombination at the dye/semiconductor/electrolyte interface is further
      investigated by SECM. A theoretical model is applied to interpret the current
      response at the tip under short-circuit conditions, providing important
      information on factors that govern the dynamics of dye-regeneration onto the dye
      sensitized heterojunction.

PMID- 24729528
TI  - Texture analysis of T1 - and T2 -weighted MR images and use of probabilistic
      neural network to discriminate posterior fossa tumours in children.
AB  - Brain tumours are the most common solid tumours in children, representing 20% of
      all cancers. The most frequent posterior fossa tumours are medulloblastomas,
      pilocytic astrocytomas and ependymomas. Texture analysis (TA) of MR images can be
      used to support the diagnosis of these tumours by providing additional
      quantitative information. MaZda software was used to perform TA on T1 - and T2 
      weighted images of children with pilocytic astrocytomas, medulloblastomas and
      ependymomas of the posterior fossa, who had MRI at Birmingham Children's Hospital
      prior to treatment. The region of interest was selected on three slices per
      patient in Image J, using thresholding and manual outlining. TA produced 279
      features, which were reduced using principal component analysis (PCA). The
      principal components (PCs) explaining 95% of the variance were used in a linear
      discriminant analysis (LDA) and a probabilistic neural network (PNN) to classify
      the cases, using DTREG statistics software. PCA of texture features from both T1 
      and T2 -weighted images yielded 13 PCs to explain >95% of the variance. The PNN
      classifier for T1 -weighted images achieved 100% accuracy on training the data
      and 90% on leave-one-out cross-validation (LOOCV); for T2 -weighted images, the
      accuracy was 100% on training the data and 93.3% on LOOCV. A PNN classifier with
      T1 and T2 PCs achieved 100% accuracy on training the data and 85.8% on LOOCV. LDA
      classification accuracies were noticeably poorer. The features found to hold the
      highest discriminating potential were all co-occurrence matrix derived, where
      adjacent pixels had highly correlated intensities. This study shows that TA can
      be performed on standard T1 - and T2 -weighted images of childhood posterior
      fossa tumours using readily available software to provide high diagnostic
      accuracy. Discriminatory features do not correspond to those used in the clinical
      interpretation of the images and therefore provide novel tumour information.

PMID- 24729529
TI  - Modeling climate impact on an emerging disease, the Phytophthora alni-induced
      alder decline.
AB  - Alder decline caused by Phytophthora alni is one of the most important emerging
      diseases in natural ecosystems in Europe, where it has threatened riparian
      ecosystems for the past 20 years. Environmental factors, such as mean site
      temperature and soil characteristics, play an important role in the occurrence of
      the disease. The objective of the present work was to model and forecast the
      effect of environment on the severity of alder Phytophthora outbreaks, and to
      determine whether recent climate change might explain the disease emergence. Two
      alder sites networks in NE and SW France were surveyed to assess the crown health
      of trees; the oomycete soil inoculum was also monitored in the NE network. The
      main factors explaining the temporal annual variation in alder crown decline or
      crown recovery were the mean previous winter and previous summer temperatures.
      Both low winter temperatures and high summer temperatures were unfavorable to the
      disease. Cold winters promoted tree recovery because of poor survival of the
      pathogen, while hot summer temperature limited the incidence of tree decline. An
      SIS model explaining the dynamics of the P. alni-induced alder decline was
      developed using the data of the NE site network and validated using the SW site
      network. This model was then used to simulate the frequency of declining alder
      over time with historical climate data. The last 40 years' weather conditions
      have been generally favorable to the establishment of the disease, indicating
      that others factors may be implicated in its emergence. The model, however,
      showed that the climate of SW France was much more favorable for the disease than
      that of the Northeast, because it seldom limited the overwintering of the
      pathogen. Depending on the European area, climate change could either enhance or
      decrease the severity of the alder decline.

PMID- 24729530
TI  - Induction of the mesenchymal to epithelial transition by demethylation- activated
      microRNA-200c is involved in the anti-migration/invasion effects of arsenic
      trioxide on human breast cancer cells.
AB  - Breast cancer is a major health problem worldwide. Current standard practices for
      treatment of breast cancer are less than satisfactory because of high rates of
      metastasis. Arsenic trioxide (As(2)O(3)), which induces demethylation of DNA and
      causes apoptosis, has been used as an anti-tumor agent. Little is known, however,
      regarding its anti-metastatic effects. The microRNA-200c (miR-200c), which is
      frequently lowly expressed in triple negative breast cancers (TNBCs), inhibits
      metastasis by inducing the mesenchymal to epithelial transition (MET). Here, we
      report that As(2)O(3) attenuates the migratory and invasive capacities of breast
      cancer cells, MDA-MB-231 and BT-549. Notably, As(2)O(3) induces an MET in vitro
      and in vivo, as determined by the increased expression of the epithelial marker,
      E-cadherin and decreased expressions of mesenchymal markers, N-cadherin and
      vimentin. Moreover, As(2)O(3) up-regulates the expression of miR-200c through
      demethylation. Over-expression of miR-200c enhances the expression of E-cadherin
      and decreases the expressions of N-cadherin and vimentin. Further, in MDA-MB-231
      cells exposed to As(2)O(3), knockdown of miR-200c blocks the As(2)O(3) -induced
      MET. Finally, in MDA-MB-231 and BT-549 cells exposed to As(2)O(3), knockdown of
      miR-200c decreases the As(2)O(3) -induced inhibition of the migratory and
      invasive capacities. By identifying a mechanism whereby As(2)O(3) regulates miR
      200c and MET, the results establish the anti-migration/invasion potential of
      arsenic trioxide.

PMID- 24729531
TI  - Determinants of vitamin D levels in men receiving androgen deprivation therapy
      for prostate cancer.
AB  - PURPOSE: Studies found an association between decreased 25-OH vitamin D blood
      level and prostate cancer progression. Vitamin D supplementation is controversial
      and dosage recommendations inconsistent. This study identified factors associated
      with 25-OH vitamin D levels and whether vitamin D supplementation with 800 IU/day
      raised vitamin D levels in prostate cancer patients receiving androgen
      deprivation therapy (ADT). DATA SOURCES: We recruited 108 men treated with ADT
      for >=9 months from eight cancer and urology practices. Sections of the NHANES
      2005-2006 questionnaire and Canadian Fitness Survey were completed identifying
      age, ethnicity, length of ADT use, calcium supplementation >=1000 IU mg/day, body
      mass index, exercise, alcohol and tobacco use, and vitamin D supplementation
      >=800 IU/daily. Blood was collected for 25-OH vitamin D analysis. CONCLUSIONS:
      The majority of men (66%) had blood levels of 25-OH vitamin D <32 ng/mL.
      Regression analysis showed vitamin D supplementation (beta = 6.556, CI 1.463,
      11.650; p = .012) and African American ethnicity (beta = -7.816, CI -12.996, 
      2.635; p = .003) is associated with 25-OH vitamin D level after controlling age
      and tobacco use. PRACTICE IMPLICATIONS: Findings support current recommendations
      for supplementation with >=800 IU vitamin D/day for men receiving ADT. Nurse
      practitioners caring for prostate cancer patients receiving ADT should include
      vitamin D monitoring and supplementation.

PMID- 24729532
TI  - Transparent stakeholder engagement in practice: Lessons learned from applying
      comprehensive environmental assessment to research planning for nanomaterials.
AB  - As efforts to develop new applications of engineered nanoscale materials (ENMs)
      continue to grow, so too has interest in the environmental, health, and safety
      (EHS) implications of these materials. However, thorough evaluation and
      interpretation of such implications could require substantial resources (e.g.,
      estimated as >$120 million per year in federal funding 2013-2017). A structured,
      strategic approach for transparently planning research would support improved
      linkages between ENM research and risk assessments, and thereby enhance the
      utility of financial and other resources for EHS studies of ENMs. For this
      reason, we applied Comprehensive Environmental Assessment (CEA) as an approach to
      provide transparent input into research planning for 2 types of ENMs: nanoscale
      titanium dioxide and nanoscale silver. For each of these CEA applications, we
      employed a collective judgment method known as Nominal Group Technique (NGT) in 2
      workshops sponsored by the US Environmental Protection Agency (USEPA). The
      objective of this paper is to present the outcomes of these CEA applications in
      the context of how our methodology can inform future efforts to identify
      collective goals in science (e.g., research priorities) through structured
      decision support approaches. Outcomes include clear lists of research priorities
      for each ENM developed through transparently engaging stakeholders having diverse
      technical and sector perspectives. In addition, we identified several procedural
      aspects that could be refined, including emphasizing breakout group interactions,
      identifying broad information priorities before more detailed research questions,
      and using rating rather than ranking prioritization methods. Beyond the research
      directions identified for specific ENMs, lessons learned about engaging
      stakeholders in research planning are expected to inform future research planning
      efforts for ENMs and other emerging materials across the scientific community.

PMID- 24729533
TI  - Cognitive problems among breast cancer survivors: loneliness enhances risk.
AB  - BACKGROUND: Cancer survivors often experience cognitive difficulties after
      treatment completion. Although chemotherapy enhances risk for cognitive problems,
      it is likely only one piece of a complex puzzle that explains survivors'
      cognitive functioning. Loneliness may be one psychosocial risk factor. The
      current studies included both subjective and objective cognitive measures and
      tested whether lonelier breast cancer survivors would have more concentration and
      memory complaints and experience more concentration difficulties than their less
      lonely counterparts. METHODS: The relationship between loneliness and cognitive
      function was tested among three samples of breast cancer survivors. Study 1 was a
      sample of breast cancer survivors (n = 200) who reported their concentration and
      memory problems. Study 2a was a sample of breast cancer survivors (n = 185) and
      noncancer controls (n = 93) who reported their concentration and memory problems.
      Study 2b was a subsample of Study 2a breast cancer survivors (n = 22) and
      noncancer controls (n = 21) who completed a standardized neuropsychological test
      assessing concentration. RESULTS: Studies 1 and 2a revealed that lonelier women
      reported more concentration and memory problems than less lonely women. Study 2b
      utilized a standardized neuropsychological continuous performance test and
      demonstrated that lonelier women experienced more concentration problems than
      their less lonely counterparts. CONCLUSIONS: These studies demonstrated that
      loneliness is linked to concentration and memory complaints and the experience of
      concentration problems among breast cancer survivors. The results were also
      highly consistent across three samples of breast cancer survivors. These data
      suggest that loneliness may be a risk factor for cognitive difficulties among
      cancer survivors.

PMID- 24729534
TI  - Measurement site influences abdominal subcutaneous and visceral adipose tissue in
      obese adolescents before and after exercise.
AB  - BACKGROUND/OBJECTIVES: The objective of this study was to determine if abdominal
      adipose tissue (AT) measurement site influences the association between baseline
      and change in abdominal subcutaneous (ASAT) and visceral AT (VAT), and metabolic
      risk factors in obese adolescents. METHODS: Fifty-five obese adolescents (14.9 +/
      1.7 years; 51% male; 42% white) participated in an aerobic or resistance
      exercise intervention three times/week for 3 months. We compared the association
      between changes in abdominal AT area (spanning 5 cm below to 15 cm above L4-L5)
      and volume measured by magnetic resonance imaging with concomitant changes in
      metabolic risk. RESULTS: All AT areas were significantly (p < 0.05) correlated
      with the respective volume at baseline and follow-up. Baseline VAT areas at 5 and
      10 cm above L4-L5 were more strongly associated with VAT volume than VAT area at
      L4-L5 (p < 0.05). After the intervention, changes in the area at 5 and 10 cm
      above L4-L5 were more strongly associated with changes in AT volumes than changes
      in L4-L5 (p < 0.05). Changes in abdominal AT volumes were more strongly
      associated with insulin area under the curve than any single-slice abdominal AT
      area. CONCLUSIONS: The measurement site for abdominal AT has significant
      influence on the relationships with total VAT or ASAT and metabolic risk factors
      in obese adolescents before and after an exercise intervention.

PMID- 24729535
TI  - Location and conformation of amyloid beta(25-35) peptide and its sequence
      shuffled peptides within membranes: implications for aggregation and toxicity in
      PC12 cells.
AB  - Extracellular deposits of amyloid beta (Abeta) aggregates in the brain is the
      hallmark of Alzheimer's disease. We present the configurations (location and
      conformation) and the interfacial folding and membrane insertion mechanisms of
      Abeta fragments, wild-type Abeta(25-35), Abeta(35-25), and a sequence-shuffled
      peptide [Abeta(25-35)-shuffled] from Abeta(25-35) within membranes by replica
      exchange molecular dynamics simulations. Although these peptides have the same
      amino acid composition, simulations show they have distinct locations and
      conformations within membranes. Moreover, our in vitro experiments show that
      these peptides have distinct neurotoxicities. We rationalize the distinct
      neurotoxicities of these peptides in terms of their simulated locations and
      conformations in membranes. This work provides another view that complements the
      general hydrophobicity-toxicity views, to better explain the neurotoxicity of
      Abeta peptides.

PMID- 24729536
TI  - Coronene encapsulation in single-walled carbon nanotubes: stacked columns,
      peapods, and nanoribbons.
AB  - Encapsulation of coronene inside single-walled carbon nanotubes (SWNTs) was
      studied under various conditions. Under high vacuum, two main types of molecular
      encapsulation were observed by using transmission electron microscopy: coronene
      dimers and molecular stacking columns perpendicular or tilted (45-60 degrees )
      with regard to the axis of the SWNTs. A relatively small number of short
      nanoribbons or polymerized coronene molecular chains were observed. However,
      experiments performed under an argon atmosphere (0.17 MPa) revealed reactions
      between the coronene molecules and the formation of hydrogen-terminated graphene
      nanoribbons. It was also observed that the morphology of the encapsulated
      products depend on the diameter of the SWNTs. The experimental results are
      explained by using density functional theory calculations through the energies of
      the coronene molecules inside the SWNTs, which depend on the orientation of the
      molecules and the diameter of the tubes. 

PMID- 24729537
TI  - Motivational interviewing targeting diet and physical activity improves adherence
      to paediatric obesity treatment: results from the MI Values randomized controlled
      trial.
AB  - BACKGROUND: Adherence is a challenge in obesity treatment. Motivational
      interviewing (MI) may promote patient adherence. MI Values is a randomized
      controlled trial of MI implemented as an adjunct to an adolescent obesity
      treatment [Teaching Encouragement Exercise Nutrition Support (T.E.E.N.S.)].
      OBJECTIVE: Assess effects of MI Values on T.E.E.N.S. attrition and adherence.
      METHODS: Participants were randomized to MI (n = 58) or control (n = 41). At
      weeks 1 and 10, MI participants had brief MI sessions; controls viewed health
      education videos. All participants continued with T.E.E.N.S. (biweekly dietitian
      and behavioural support visits; 3 times per week supervised physical activity).
      Assessments were repeated at baseline, 3 and 6 months. T-tests and chi-square
      analyses examined T.E.E.N.S. attrition and adherence by group. RESULTS:
      Adolescents (N = 99) were primarily African-American (73%) females (74%); age =
      13.8 +/- 1.8 years, body mass index percentile = 98.0 +/- 1.2. Compared with
      controls, MI participants had greater 3-month adherence overall (89.2% vs. 81.0%,
      P = 0.040), and to dietitian (91.3% vs. 84.0%; P = 0.046) and behavioural support
      (92.9% vs. 85.2%; P = 0.041) visits, and greater 6-month adherence overall (84.4%
      vs. 76.2%, P = 0.026) and to behavioural support visits (87.5% vs. 78.8%, P =
      0.011). CONCLUSIONS: MI enhanced adherence to this obesity intervention. MI
      Values is the first study to examine the impact of MI on treatment adherence
      among obese, primarily African-American adolescents.

PMID- 24729538
TI  - Expression pattern of the human ABC transporters in pluripotent embryonic stem
      cells and in their derivatives.
AB  - BACKGROUND: ATP-binding cassette (ABC) transporters have key roles in various
      physiological functions as well as providing chemical defense and stress
      tolerance in human tissues. In this study, we have examined the expression
      pattern of all ABC proteins in pluripotent human embryonic stem cells (hESCs) and
      in their differentiated progenies. We paid special attention to the cellular
      expression and localization of multidrug transporter ABC proteins. METHODS: Stem
      cell differentiation was carried out without chemical induction or cell sorting,
      and specialized cell types were separated mechanically. Cellular features
      regarding pluripotency and tissue identity, as well as ABC transporter expression
      were studied by flow cytomtery, immuno-microscopy, and qPCR-based low-density
      arrays. RESULTS: Pluripotent hESCs and differentiated cell types (cardiomyocytes,
      neuronal cells, and mesenchymal stem cells) were distinguished by morphology,
      immunostaining markers, and selected mRNA expression patterns. We found that the
      mRNA expression levels of the 48 human ABC proteins also clearly distinguished
      the pluripotent and the respective differentiated cell types. When multidrug and
      lipid transporter ABC protein expression was examined by using well characterized
      specific antibodies by flow cytometry and confocal microscopy, the protein
      expression data corresponded well to the mRNA expression results. Moreover, the
      cellular localization of these important human ABC transporter proteins could be
      established in the pluripotent and differentiated hESC derived samples.
      CONCLUSIONS: These studies provide valuable information regarding ABC protein
      expression in human stem cells and their differentiated offspring. The results
      may also help to obtain further information concerning the specialized cellular
      functions of selected ABC transporters.

PMID- 24729539
TI  - TBC1D24 mutation causes autosomal-dominant nonsyndromic hearing loss.
AB  - Hereditary hearing loss is extremely heterogeneous. Over 70 genes have been
      identified to date, and with the advent of massively parallel sequencing, the
      pace of novel gene discovery has accelerated. In a family segregating progressive
      autosomal-dominant nonsyndromic hearing loss (NSHL), we used OtoSCOPE(r) to
      exclude mutations in known deafness genes and then performed segregation mapping
      and whole-exome sequencing to identify a unique variant, p.Ser178Leu, in TBC1D24
      that segregates with the hearing loss phenotype. TBC1D24 encodes a GTPase
      activating protein expressed in the cochlea. Ser178 is highly conserved across
      vertebrates and its change is predicted to be damaging. Other variants in TBC1D24
      have been associated with a panoply of clinical symptoms including autosomal
      recessive NSHL, syndromic hearing impairment associated with onychodystrophy,
      osteodystrophy, mental retardation, and seizures (DOORS syndrome), and a wide
      range of epileptic disorders. 

PMID- 24729540
TI  - Reduced retinoids and retinoid receptors' expression in pancreatic cancer: A link
      to patient survival.
AB  - Pancreatic ductal adenocarcinoma (PDAC) represents one of the deadliest cancers
      in the world. All-trans retinoic acid (ATRA) is the major physiologically active
      form of vitamin A, regulating expression of many genes. Disturbances of vitamin A
      metabolism are prevalent in some cancer cells. The main aim of this work was to
      investigate deeply the components of retinoid signaling in PDAC compared to in
      the normal pancreas and to prove the clinical importance of retinoid receptor
      expression. For the study, human tumor tissues obtained from PDAC patients and
      murine tumors from the orthotopic Panc02 model were used for the analysis of
      retinoids, using high performance liquid chromatography mass spectrometry and
      real-time RT-PCR gene expression analysis. Survival probabilities in univariate
      analysis were estimated using the Kaplan-Meier method and the Cox proportional
      hazards model was used for the multivariate analysis. In this work, we showed for
      the first time that the ATRA and all-trans retinol concentration is reduced in
      PDAC tissue compared to their normal counterparts. The expression of RARalpha and
      beta as well as RXRalpha and beta are down-regulated in PDAC tissue. This reduced
      expression of retinoid receptors correlates with the expression of some markers
      of differentiation and epithelial-to-mesenchymal transition as well as of cancer
      stem cell markers. Importantly, the expression of RARalpha and RXRbeta is
      associated with better overall survival of PDAC patients. Thus, reduction of
      retinoids and their receptors is an important feature of PDAC and is associated
      with worse patient survival outcomes.

PMID- 24729541
TI  - Climate change and geothermal ecosystems: natural laboratories, sentinel systems,
      and future refugia.
AB  - Understanding and predicting how global warming affects the structure and
      functioning of natural ecosystems is a key challenge of the 21st century.
      Isolated laboratory and field experiments testing global change hypotheses have
      been criticized for being too small-scale and overly simplistic, whereas surveys
      are inferential and often confound temperature with other drivers. Research that
      utilizes natural thermal gradients offers a more promising approach and
      geothermal ecosystems in particular, which span a range of temperatures within a
      single biogeographic area, allow us to take the laboratory into nature rather
      than vice versa. By isolating temperature from other drivers, its ecological
      effects can be quantified without any loss of realism, and transient and
      equilibrial responses can be measured in the same system across scales that are
      not feasible using other empirical methods. Embedding manipulative experiments
      within geothermal gradients is an especially powerful approach, informing us to
      what extent small-scale experiments can predict the future behaviour of real
      ecosystems. Geothermal areas also act as sentinel systems by tracking responses
      of ecological networks to warming and helping to maintain ecosystem functioning
      in a changing landscape by providing sources of organisms that are preadapted to
      different climatic conditions. Here, we highlight the emerging use of geothermal
      systems in climate change research, identify novel research avenues, and assess
      their roles for catalysing our understanding of ecological and evolutionary
      responses to global warming. 

PMID- 24729542
TI  - Epithelial-mesenchymal transitions in bronchopulmonary dysplasia of newborn rats.
AB  - BACKGROUND: Bronchopulmonary dysplasia (BPD) is a major threat to the health of
      premature infants yet its pathogenesis is not fully understood. Epithelial
      mesenchymal transition (EMT) of lung epithelial cells may lead to BPD. OBJECTIVE:
      To investigate the potential occurrence of EMT in a newborn rat model of BPD.
      METHODS: Newborn rats were exposed to a hyperoxic environment within 12 hr of
      birth. Lung tissue and isolated alveolar epithelial type II cells (AT2 cells)
      were collected on Days 1, 3, 7, 14, and 21 after hyperoxic exposure. Pathological
      changes in lung tissue, alveolar development, ultrastructural changes in AT2
      cells, co-expression of surfactant associated surfactant protein C (SPC), and
      alpha-smooth muscle actin (alpha-SMA) were investigated. The relative expression
      of SPC, alpha-SMA, E-cadherin, and N-cadherin were investigated in lung tissue
      and isolated AT2 cells. RESULTS: In lung tissue, alveolar development was
      attenuated from Day 7 onwards in the BPD model group; co-expression of SPC and
      alpha-SMA and ultrastructural changes typical of EMT were observed in AT2 cells
      from rats in the BPD group. SPC and alpha-SMA expression levels were higher in
      tissue samples from the BPD group than in control samples. Beginning on Day 7,
      evidence of a switch from E-cadherin to N-cadherin expression was observed in BPD
      lung tissue sample and in isolated AT2 cells. CONCLUSION: EMT of AT2 cells
      occurred in the hyperoxia-induced newborn rat BPD model and resulted in
      attenuated alveolar development as a portion of the myofibroblasts accumulated in
      the lung originated from AT2 cells via EMT.

PMID- 24729543
TI  - Using attachment theory to inform the design and delivery of mental health
      services: a systematic review of the literature.
AB  - PURPOSE: The aim of this review was to propose and describe the design and
      delivery of an attachment-informed general mental health service. METHOD: We
      systematically searched the PsycINFO, MEDLINE, Web of Knowledge, COPAC, CINAHL,
      and Science Direct databases from 1960 to 2013. We also searched reference lists
      of relevant papers and directly contacted authors in the field. Literature
      describing attachment theory and its applicability in designing and delivering
      general mental health services was synthesized using thematic analysis. Papers
      published in English, books or chapters in edited books that described applying
      attachment theory in designing and delivering mental health services for adults
      and adolescents were included in the review. Of the 1,105 articles identified, 14
      met inclusion criteria for the review. Eight key themes, and four subthemes, were
      extracted and organized to reflect the experience of a service user moving
      through the mental health system. RESULTS: Key themes extracted were as follows:
      service policy and evaluation; referrals; assessment and formulation;
      intervention; support for staff; support for carers; moving on; and potential
      service benefits. Papers reviewed suggested that service users with severe mental
      health problems have attachment needs that should be met in general mental health
      services. CONCLUSIONS: Attachment theory provides a useful framework to inform
      the design and delivery of general mental health services. The resource
      implications for services are discussed, as are limitations of the review and
      recommendations for future research. PRACTITIONER POINTS: Attachment theory
      should be used to inform the design and delivery of general mental health
      services. Mental health services should evaluate the extent to which they meet
      service users' attachment needs. Attachment-informed mental health services
      should assess outcomes, including cost-effectiveness over time. Papers included
      in this review focus on long-stay residential care or secure services and there
      is a limited experimental evidence base to show that providing an attachment
      informed service improves patient outcomes.

PMID- 24729545
TI  - Reply: To PMID 23983095.

PMID- 24729544
TI  - Inhibition of cathepsin activity in a cell-based assay by a light-activated
      ruthenium compound.
AB  - Light-activated inhibition of cathepsin activity was demonstrated in a cell-based
      assay. Inhibitors of cathepsin K, Cbz-Leu-NHCH2 CN (2) and Cbz-Leu-Ser(OBn)-CN
      (3), were caged within the complexes cis-[Ru(bpy)2 (2)2 ]Cl2 (4) and cis
      [Ru(bpy)2 (3)2 ](BF4 )2 (5) (bpy=2,2'-bipyridine) as 1:1 mixtures of Delta and
      Lambda stereoisomers. Complexes 4 and 5 were characterized by (1) H NMR, IR, and
      UV/Vis spectroscopies and electrospray mass spectrometry. Photochemical
      experiments confirm that 4 releases two molecules of 2 upon exposure to visible
      light for 15 min, whereas release of 3 by 5 requires longer irradiation times.
      IC50 determinations against purified cathepsin K under light and dark conditions
      with 4 and 5 confirm that inhibition is enhanced from 35- to 88-fold,
      respectively, upon irradiation with visible light. No apparent toxicity was
      observed for 4 in the absence or presence of irradiation in bone marrow
      macrophage (BMM) or PC3 cells, as determined by MTT assays, at concentrations up
      to 10 MUM. Compound 5 is well tolerated at lower concentrations (<1 MUM), but
      does show growth-inhibitory effects at higher concentrations. Confocal microscopy
      experiments show that 4 decreases intracellular cathepsin activity in osteoclasts
      with light activation. These results support the further development of caged
      nitrile-based inhibitors as chemical tools for investigating spatial aspects of
      proteolysis within living systems.

PMID- 24729546
TI  - Benzyl isothiocyanate suppresses high-fat diet-stimulated mammary tumor
      progression via the alteration of tumor microenvironments in obesity-resistant
      BALB/c mice.
AB  - We previously reported that a high-fat diet (HFD) and M2-macrophages induce
      changes in tumor microenvironments and stimulate tumor growth and metastasis of
      4T1 mammary cancer cells in BALB/c mice. In this study, we attempted to determine
      whether benzyl isothiocyanate (BITC) inhibits HFD-induced changes in tumor
      progression and in tumor microenvironments. Four groups of female BALB/c mice (4
      week-old) were fed on a control diet (CD, 10 kcal% fat) and HFD (60 kcal% fat)
      containing BITC (0, 25, or 100 mg/kg diet) for 20 weeks. Following 16 weeks of
      feeding, 4T1 cells (5*10(4) cells) were injected into the mammary fat pads, and
      animals were killed 30 d after the injection. HFD feeding increased solid tumor
      growth and the number of tumor nodules in the lung and liver, as compared to the
      CD group, and these increases were inhibited by BITC supplementation. The number
      of lipid vacuoles, CD45+ leukocytes and CD206+ M2-macrophages, expression of
      Ki67, levels of cytokines/chemokines, including macrophage-colony stimulating
      factor (M-CSF) and monocyte chemoattractant protein-1, and mRNA levels of F4/80,
      CD86, Ym1, CD163, CCR2, and M-CSF receptor were increased in the tumor tissues of
      HFD-fed mice, and these increases were inhibited by BITC supplementation. In
      vitro culture results demonstrated that BITC inhibited macrophage migration as
      well as lipid droplet accumulation in 3T3-L1 cells. These results suggest that
      suppression of lipid accumulation and macrophage infiltration in tumor tissues
      may be one of the mechanisms by which BITC suppresses tumor progression in HFD
      fed mice.

PMID- 24729547
TI  - A dominant mutation in the stereocilia-expressing gene TBC1D24 is a probable
      cause for nonsyndromic hearing impairment.
AB  - Mutations in TBC1D24 have been linked to a variety of epileptic syndromes and
      recently to syndromic hearing impairment DOORS syndrome and nonsyndromic hearing
      impairment DFNB86. All TBC1D24 mutations reported so far were inherited in the
      recessive mode. In a dominant family segregated with late-onset, progressive,
      nonsyndromic hearing impairment, linkage analysis revealed a 2.07 Mb candidate
      region on chromosome 16p13.3 that contains TBC1D24. Whole-exome sequencing
      identified a heterozygous p.Ser178Leu variant of TBC1D24 as the only candidate
      mutation segregating with the hearing loss within the family. In perinatal mouse
      cochlea, we detected a restricted expression of Tbc1d24 in the stereocilia of the
      hair cells as well as in the spiral ganglion neurons. Our study suggested that
      the p.Ser178Leu mutation of TBC1D24 is a probable cause for dominant,
      nonsyndromic hearing impairment. Identification of TBC1D24 as the stereocilia
      expressing gene may shed new light on its specific function in the inner ear. 

PMID- 24729548
TI  - Use of inhaled iloprost in children with pulmonary hypertension.
AB  - Pulmonary hypertension (PH) in children is a serious disorder, for which the
      major goal of treatment is to prevent progressive vascular remodeling, and
      improve clinical status and survival. Iloprost is approved for the treatment of
      PH in adults; however, few studies have evaluated its effects in children. The
      objective of this study is to analyze the long-term effects of inhaled iloprost
      treatment in children with PH. A retrospective study was conducted in patients
      treated with iloprost between 2000 and 2012. Patients with left-right cardiac
      shunt and persistent PH of the newborn were excluded. The cohort comprised 22
      patients (15 females) with a median age of 2.6 years. Twelve patients had
      pulmonary arterial hypertension including idiopathic (n = 6), hereditary (n = 2)
      and associated (congenital heart disease [n = 3], and schistosomiasis [n = 1]).
      One patient had pulmonary veno-occlusive disease, six patients had PH secondary
      to lung disease and three had multifactorial PH. Median mean pulmonary arterial
      pressure was 55 mmHg and median pulmonary vascular resistance was 15.5 Wood
      units. Good tolerability was observed, with the exception of one case of
      recurring abdominal pain. PH resolved in two patients, with functional capacity
      improvement in 10 patients and stabilization in three patients. The clinical
      condition of six patients deteriorated; two died, and two received lung
      transplants. In conclusion, the results of this uncontrolled study showed that
      iloprost was effective and well tolerated in children. However, further research
      is needed to support this study, as PH is a serious condition that can require
      organ transplantation or result in death.

PMID- 24729551
TI  - Advancing OCT algorithmic standardization.

PMID- 24729552
TI  - High-throughput screening of metal-N-heterocyclic carbene complexes against
      biofilm formation by pathogenic bacteria.
AB  - A set of molecules including a majority of metal-N-heterocyclic carbene (NHC)
      complexes (metal=Ag, Cu, and Au) and azolium salts were evaluated by high
      throughput screening of their activity against biofilm formation associated with
      pathogenic bacteria. The anti-planktonic effects were compared in parallel.
      Representative biofilm-forming strains of various genera were selected (Listeria,
      Pseudomonas, Staphylococcus, and Escherichia). All the compounds were tested at 1
      mg L(-1) by using the BioFilm Ring Test. An information score (IS, sum of the
      activities) and an activity score (AS, difference between anti-biofilm and anti
      planktonic activity) were determined from normalized experimental values to
      classify the most active molecules against the panel of bacterial strains. With
      this method we identified lipophilic Ag(I) and Cu(I) complexes possessing
      aromatic groups on the NHC ligand as the most efficient at inhibiting biofilm
      formation.

PMID- 24729553
TI  - Reply to Paltiel et al.

PMID- 24729554
TI  - Misinterpretation of HIV preexposure prophylaxis findings.

PMID- 24729555
TI  - Reply to Sachdev et al.

PMID- 24729556
TI  - Intentions to prescribe preexposure prophylaxis are associated with self-efficacy
      and normative beliefs.

PMID- 24729557
TI  - Musculoskeletal ultrasound and anatomy: comment on the article by Navarro-Zarza
      et al.

PMID- 24729558
TI  - Revealing the hidden faults in the SE flank of Mt. Etna using radon in-soil gas
      measurement.
AB  - Although there are many methods for investigating tectonic structures, many
      faults remain hidden, and they can endanger the life and property of people
      living along them. The slopes of volcanoes are covered with such hidden faults,
      near which strong earthquakes and gas releases can appear. Revealing hidden
      faults can therefore contribute significantly to the protection of people living
      in volcanic areas. In the study, seven different techniques were used for making
      measurements of in-soil radon concentrations in order to search for hidden faults
      on the SE flank of the Mt. Etna volcano. These reported methods had previously
      been proved to be useful tools for investigating fault structures. The main aim
      of the experiment presented here was to evaluate the usability of these methods
      in the geological conditions of the Mt. Etna region, and to find the best place
      for continual radon monitoring using a permanent station in the near future. 

PMID- 24729559
TI  - Experimental studies about the ratio between 210Po deposited on surfaces and
      retrospective indoor 222Rn concentrations.
AB  - Measurements of radon concentration may not be sufficiently representative for
      the cumulative total exposure suffered by a person throughout his life.
      Retrospective dosimetry can help estimating from the direct measurement of 210Po
      (descendant of 222Rn) implanted on surfaces, because this quantity is related
      (through the conversion factor) with the mean indoor 222Rn concentration existing
      in a room for long time. This factor depends on multiple variables. Theoretical
      models can provide some values. Experiments are tedious and very time consuming.
      The 210Po activity concentration was measured in mirrors, which were previously
      exposed to 222Rn concentrations under real environmental conditions. This work
      deals with the preliminary results in two known places (a room and a cave), which
      have very different characteristics, in order to show experimentally the large
      differences found in the values of this factor.

PMID- 24729560
TI  - International intercomparison of measuring instruments for radon/thoron gas and
      radon short-lived daughter products in the NRPI Prague.
AB  - During the 7th European Conference on Protection Against Radon at Home and at
      Work held in the autumn of 2013 in Prague, the second intercomparison of
      measuring instruments for radon and its short-lived decay products and the first
      intercomparison of radon/thoron gas discriminative passive detectors in mix field
      of radon/thoron were organised by and held at the Natural Radiation Division of
      the National Radiation Protection Institute (NRPI) in Prague. In total, 14
      laboratories from 11 different countries took part in the 2013 NRPI
      intercomparison. They submitted both continuous monitors for the measurement of
      radon gas and equivalent equilibrium radon concentration in a big NRPI chamber
      (48 m3) and sets of passive detectors including radon/thoron discriminative for
      the measurement of radon gas in the big chamber and thoron gas in a small thoron
      chamber (150 dm3).

PMID- 24729561
TI  - MCNPX evaluation of gamma spectrometry results in high radon concentration areas.
AB  - The radon concentration in underground workplaces may reach tens of thousands of
      Bq m(-3). A simple MCNPXTM Monte Carlo (MC) model of a cave was developed to
      estimate the influence of radon on the in situ gamma spectrometry results in
      various geometries and radon concentrations. The detector total count rate was
      obtained as the sum of the individual count rates due to 214Bi in the air, radon
      in the walls and deposition of radon daughters on surfaces. The MC model was then
      modified and used in the natural conditions of the Mladec Caves, Czech Republic.
      The content of 226Ra was calculated from laboratory gamma spectrometry
      measurements, and the concentrations of unattached and attached 214Bi were
      measured using the FRITRA4 device (SMM-Prague). We present a comparison of the
      experimental results with results calculated by the MCNPXTM model of the Gamma
      Surveyor spectrometry probe (GF Instruments) with a 3"*3" NaI(Tl) detector and a
      2"*2" BGO detector.

PMID- 24729562
TI  - Radon measurement and mitigation activity in Finland.
AB  - Radon prevention, measurement and mitigation activities have been increasing in
      Finland during the 2000s. Nowadays, many municipal authorities, especially those
      located in high-radon areas, require radon prevention measures. This has
      activated radon measurements. Owners of new houses having radon piping installed
      under the floor slab are the most active group to measure and reduce the found
      high-radon values. Their radon awareness is apparently better than on the
      average, and the existing piping makes it easier and cheaper to reduce the radon
      levels. Local campaigns involving invitation flyers mailed to the residents have
      been a cost-effective means to activate measurements of older houses. So far
      116,611 dwellings in low-rise residential buildings have been measured. At least
      15% of the 16,860 dwellings found to exceed the reference level of 400 Bq m(-3)
      had their indoor radon level reduced below that.

PMID- 24729563
TI  - Dealing with the increased radon concentration in thermally retrofitted
      buildings.
AB  - The influence of energy-saving measures on indoor radon concentration has been
      studied on the basis of a family house made of clinker concrete wall panels
      containing from 1000 up to 4000 Bq kg(-1) of 226Ra. Thermal retrofitting based on
      installing external thermal insulation composite system on the building envelope
      and replacing existing windows by new ones decreased the annual energy need for
      heating 2.8 times, but also reduced the ventilation rate to values<0.1 h(-1). As
      a consequence, the 1-y average indoor radon concentration values increased 3.4
      times from 337 to 1117 Bq m(-3). The additional risk of lung cancer in the
      thermally retrofitted house increased to a value that is 125 % higher than before
      conversion. Methods for dealing with this enhanced risk by increasing the
      ventilation rate are discussed. Recovery of investments and the energy
      consequences of increased ventilation are studied in a long-term perspective.

PMID- 24729564
TI  - Monitoring trends in civil engineering and their effect on indoor radon.
AB  - In this paper, the importance of monitoring new building concepts is discussed.
      The effect of energy-efficient construction technologies on indoor radon is
      presented in more detail. Comparing the radon levels of about 100 low-energy and
      passive houses in Austria with radon levels in conventional new houses show that,
      in energy-efficient new houses, the radon level is about one-third lower than in
      conventional new houses. Nevertheless, certain features or bad practice may cause
      high radon levels in energy-efficient new houses. Recommendations to avoid
      adverse effects were set up. Furthermore, the paper deals with the effect of
      thermal retrofitting on indoor radon. Results from a Swiss study where 163
      dwellings were measured before and after thermal retrofit yield an increase of
      the radon level of 26% in average. Among the various retrofit measures, replacing
      windows has the greatest impact on the indoor radon level.

PMID- 24729565
TI  - Radon as a natural tracer for gas transport within uranium waste rock piles.
AB  - Acid mine drainage (AMD) has been identified as the main cause for outflow of
      acid water and radioactive/non-radioactive contaminants. AMD encompasses pyrites
      oxidation when water and oxygen are available. AMD was identified in uranium
      waste rock piles (WRPs) of Industrias Nucleares do Brasil-Caldas facility
      (Brazilian uranium mine), resulting in high costs for water treatment. AMD
      reduction is the main challenge, and scientific investigation has been conducted
      to understand oxygen and water transportation within WRPs, where 222Rn is used as
      natural tracer for oxygen transportation. The study consists of soil radon gas
      mapping in the top layer of WRP4 using active soil gas pumping, radon adsorption
      in active charcoal and 222Rn determination using high-resolution gamma-ray
      spectrometry. A sampling network of 71 points was built where samples were
      collected at a depth of 40 cm. Soil radon gas concentration ranged from 33.7 to
      1484.2 kBq m(-3) with mean concentration of 320.7+/-263.3 kBq m(-3).

PMID- 24729566
TI  - Recommendations for analyzing and reporting TP53 gene variants in the high
      throughput sequencing era.
AB  - The architecture of TP53, the most frequently mutated gene in human cancer, is
      more complex than previously thought. Using TP53 variants as clinical biomarkers
      to predict response to treatment or patient outcome requires an unequivocal and
      standardized procedure toward a definitive strategy for the clinical evaluation
      of variants to provide maximum diagnostic sensitivity and specificity. An
      intronic promoter and two novel exons have been identified resulting in the
      expression of multiple transcripts and protein isoforms. These regions are
      additional targets for mutation events impairing the tumor suppressive activity
      of TP53. Reassessment of variants located in these regions is needed to refine
      their prognostic value in many malignancies. We recommend using the stable Locus
      Reference Genomic reference sequence for detailed and unequivocal reports and
      annotations of germ line and somatic alterations on all TP53 transcripts and
      protein isoforms according to the recommendations of the Human Genome Variation
      Society. This novel and comprehensive description framework will generate
      standardized data that are easy to understand, analyze, and exchange across
      various cancer variant databases. Based on the statistical analysis of more than
      45,000 variants in the latest version of the UMD TP53 database, we also provide a
      classification of their functional effects ("pathogenicity"). 

PMID- 24729567
TI  - Low-frequency sonication may alter surface topography of endoprosthetic
      components and damage articular cartilage without eradicating biofilms
      completely.
AB  - Two-stage exchange arthroplasty is the current standard of care for arthroplasty
      related infections. Reinfection rates up to 30% are reported, and there is
      significant morbidity for the patient. In cases of failure, arthrodesis or
      amputation may result. Ultrasonic treatment has the potential to eradicate
      biofilms and avoid two-stage exchange arthroplasty. Data in the specific context
      of arthroplasty infections is scant, and there is debate regarding optimal
      frequency and intensity of treatment. Surface topography alterations of the
      endoprosthetic components and damage to adjacent bone and cartilage have not been
      investigated. We found incomplete biofilm eradication and significant increase in
      surface roughness (maximum peak-to-valley height) of cobalt-chrome unicondylar
      knee components as well as reduction in articular cartilage thickness area from
      10 retrieved femoral heads after low-frequency sonication treatment according to
      manufacturer-specified recommendations. Our data collectively suggest that
      sonication treatment for biofilm eradication in arthroplasty infections may not
      be effective and surface topography alterations may potentially reduce implant
      longevity.

PMID- 24729568
TI  - Three-dimensional protein networks assembled by two-photon activation.
AB  - Spatial and temporal control over chemical and biological processes plays a key
      role in life and material sciences. Here we synthesized a two-photon-activatable
      glutathione (GSH) to trigger the interaction with glutathione S-transferase (GST)
      by light at superior spatiotemporal resolution. The compound shows fast and well
      confined photoconversion into the bioactive GSH, which is free to interact with
      GST-tagged proteins. The GSH/GST interaction can be phototriggered, changing its
      affinity over several orders of magnitude into the nanomolar range. Multiplexed
      three-dimensional (3D) protein networks are simultaneously generated in situ
      through two-photon fs-pulsed laser-scanning excitation. The two-photon activation
      facilitates the three-dimensional assembly of protein structures in real time at
      hitherto unseen resolution in time and space, thus opening up new applications
      far beyond the presented examples. 

PMID- 24729569
TI  - Stimulation of luminescence of mycelium of luminous fungus Neonothopanus nambi by
      ionizing radiation.
AB  - The luminescent system of higher luminous fungi is not fully understood and the
      enzyme/substrate pair of the light emission reaction has not been isolated. It
      was suggested that luminescence of fungi involves oxidase-type enzymes, and
      reactive oxygen species are important for fungal light production. Generation of
      reactive oxygen species can be stimulated by ionizing irradiation, which has not
      been studied for luminous fungi. We report the effect of X-irradiation on the
      luminescence of fungus Neonothopanus nambi. Experiments were performed with
      mycelium on a home-built setup based on an X-ray tube and
      monochromator/photomultiplier tube. Application of X-rays does not change the
      emission spectrum, but after approximately 20 min of continuous irradiation,
      light production from unsupported mycelium starts growing and increases up to
      approximately five times. After peaking, its level decreases irrespective of the
      presence of X-irradiation. After staying at a certain level, light production
      collapses to zero, which is not related to the drying of the mycelium or thermal
      impact of radiation. The observed shape of kinetics is characteristic of a
      multistage and/or chain reaction. The time profile of light production must
      reflect the current levels of radicals present in the system and/or the activity
      of enzyme complexes involved in light production.

PMID- 24729575
TI  - Monitoring triplet state dynamics with fluorescence correlation spectroscopy:
      bias and correction.
AB  - A marker's dark triplet state is of great importance in fluorescence microscopy:
      It serves as a means to switch off fluorescent markers and is thus the enabling
      element for several super-resolution methods. On the other hand, intersystem
      crossing to the electronic dark triplet state strongly reduces the fluorescence
      yield in conventional fluorescence microscopy. The ability to determine the
      kinetic parameters of transitions into the triplet state is thus of great
      importance and because fluorescence correlation spectroscopy (FCS) can be applied
      without disturbing the system under study, it is one of the preferred methods to
      do so. However, conventional FCS observations of triplet dynamics suffer from
      bias due to the spatially inhomogeneous irradiance profile of the excitation
      laser. Herein, we present a novel method to correct this bias and verify it by
      analyzing both Monte Carlo simulated and experimental data of the organic dye
      Rhodamine 110 in aqueous solution for both continuous-wave and pulsed excitation.
      Importantly, our approach can be readily generalized to most other FCS
      experiments that determine intensity dependent kinetic parameters.

PMID- 24729576
TI  - Nanobiomolecular multiprotein clusters on electrodes for the formation of a
      switchable cascadic reaction scheme.
AB  - A supramolecular multicomponent protein architecture on electrodes is developed
      that allows the establishment of bidirectional electron transfer cascades based
      on interprotein electron exchange. The architecture is formed by embedding two
      different enzymes (laccase and cellobiose dehydrogenase) and a redox protein
      (cytochrome c) by means of carboxy-modified silica nanoparticles in a multiple
      layer format. The construct is designed as a switchable dual analyte detection
      device allowing the measurement of lactose and oxygen, respectively. As the
      switching force we apply the electrode potential, which ensures control of the
      redox state of cytochrome c. The two signal chains are operating in a non
      separated matrix and are not disturbed by the other biocatalyst. 

PMID- 24729577
TI  - PET imaging of prostate tumors with 18F-Al-NOTA-MATBBN.
AB  - Overexpression of the gastrin-releasing peptide receptor (GRPR) in prostate
      cancer provides a promising target for detection the disease. MATBBN is a new
      bombesin analog originating from the GRPR antagonists with a hydrophilic linker.
      In this study NOTA-conjugated MATBBN was labeled by the Al(18)F method and the
      potential of (18)F-Al-NOTA-MATBBN for prostate tumor PET imaging was also
      evaluated. NOTA-MATBBN was radiolabeled with (18) F using Al(18)F complexes.
      Partition coefficient, in vitro stability and GRPR binding affinity were also
      determined. PET studies were performed with (18)F-Al-NOTA-MATBBN in PC-3 tumor
      bearing mice. (18)F-Al-NOTA-MATBBN can be produced within 30 min with a decay
      corrected yield of 62.5 +/- 2.1% and a radiochemical purity of >98%. The logP
      octanol-water value for the Al(18)F-labeled BBN analog was -2.40 +/- 0.07 and the
      radiotracer was stable in phosphate-buffered saline and human serum for 2 h. The
      IC50 values of displacement for the (18)F-Al-NOTA-MATBBN with MATBBN was 126.9 +/
      2.75 nm. The PC-3 tumors were clearly visible with high contrast after injection
      of the labeled peptide. At 60 min post-injection, the tumor uptakes for (18)F-Al
      NOTA-MATBBN and (18)F-FDG were 4.59 +/- 0.43 and 1.98 +/- 0.35% injected dose/g,
      and tumor to muscle uptake radios for two tracers were 6.77 +/- 1.10 and 1.78 +/-
      0.32, respectively. Dynamic PET revealed that (18) F-Al-NOTA-MATBBN was excreted
      mainly through the kidneys. GRPR-binding specificity was also demonstrated by
      reduced tumor uptake of (18)F-Al-NOTA-MATBBN after coinjection with excess
      unlabeled MATBBN peptide at 1 h post-injection. NOTA- MATBBN could be labeled
      rapidly with (18)F using one step method. (18)F-Al-NOTA-MATBBN may be a promising
      PET imaging agent for prostate cancer.

PMID- 24729578
TI  - Caulerpenyne and related bis-enol esters are novel-type inhibitors of human 5
      lipoxygenase.
AB  - Caulerpenyne (CYN) is a sesquiterpene from green algae with known inhibitory
      properties against soybean lipoxygenase. Here we introduce a detailed structure
      activity study elucidating the inhibitory effects of CYN and a library of six
      synthetic CYN analogues on isolated human 5-lipoxygenase (5-LO) and cellular 5-LO
      in polymorphonuclear leukocytes. Essential structural elements are identified and
      a structurally simplified inhibitor is introduced. The modes of 5-LO inhibition
      by CYN and the synthetic inhibitors cannot be assigned to any of the known
      categories of lipoxygenase inhibitors. These compounds clearly interfere directly
      with 5-LO and represent rather small and flexible molecules, with unique
      structures among 5-LO inhibitors identified thus far. 

PMID- 24729579
TI  - Hormesis with pesticides.

PMID- 24729580
TI  - Synthesis and 3D printing of biodegradable polyurethane elastomer by a water
      based process for cartilage tissue engineering applications.
AB  - Biodegradable materials that can undergo degradation in vivo are commonly
      employed to manufacture tissue engineering scaffolds, by techniques including the
      customized 3D printing. Traditional 3D printing methods involve the use of heat,
      toxic organic solvents, or toxic photoinitiators for fabrication of synthetic
      scaffolds. So far, there is no investigation on water-based 3D printing for
      synthetic materials. In this study, the water dispersion of elastic and
      biodegradable polyurethane (PU) nanoparticles is synthesized, which is further
      employed to fabricate scaffolds by 3D printing using polyethylene oxide (PEO) as
      a viscosity enhancer. The surface morphology, degradation rate, and mechanical
      properties of the water-based 3D-printed PU scaffolds are evaluated and compared
      with those of polylactic-co-glycolic acid (PLGA) scaffolds made from the solution
      in organic solvent. These scaffolds are seeded with chondrocytes for evaluation
      of their potential as cartilage scaffolds. Chondrocytes in 3D-printed PU
      scaffolds have excellent seeding efficiency, proliferation, and matrix
      production. Since PU is a category of versatile materials, the aqueous 3D
      printing process developed in this study is a platform technology that can be
      used to fabricate devices for biomedical applications. 

PMID- 24729582
TI  - Distortional supramolecular isomers of polyrotaxane coordination polymers:
      photoreactivity and sensing of nitro compounds.
AB  - Distortional isomers, or bond-stretch isomers, differ only in the length of one
      or more bonds, which is due to crystallographic disorder in most cases. The term
      distortional isomerism is introduced to describe the structures of polyrotaxane
      2D coordination polymers (CPs) that differ only by the relative positions in the
      neighboring entangled axles. A large ring and a long spacer ligand in 2D CPs
      yielded four different supramolecular isomers, of which two have an entangled
      polyrotaxane structure. One pair of C=C bonds in the spacer ligand is well
      aligned in one isomer and undergoes [2+2] cycloaddition reaction, whereas the
      other isomer is photoinert. They also have different sensing efficiency for
      several aromatic nitro compounds. However, both isomers show selective PL
      quenching for the Brady's reagent. Structurally similar supramolecular isomers
      with different photochemical reactivity and sensing abilities appear to be
      unprecedented.

PMID- 24729581
TI  - Molecular magnetic resonance probe targeting VEGF165: preparation and in vitro
      and in vivo evaluation.
AB  - A new method for imaging the tumor human vascular endothelial growth factor 165
      (VEGF 165) is presented. A magnetic resonance imaging (MRI) probe was prepared by
      crosslinking ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles to the
      aptamer for tumor vascular endothelial growth factor 165 (VEGF165-aptamer). The
      molecular probe was evaluated for its in vitro and in vivo activities toward
      VEGF165. Enzyme-linked immunosorbent assay showed that the VEGF165-aptamer-USPIO
      nanoparticles conjugate specifically binds to VEGF165 in vitro. A cell
      proliferation test showed that VEGF165-aptamer-USPIO seems to block the
      proliferation of human umbilical vein endothelial cells induced by free VEGF165,
      suggesting that VEGF165 is an effective target of this molecular probe. In
      xenograft mice carrying liver cancer that expresses VEGF165, T2-weighted imaging
      of the tumor displayed marked negative enhancement 3 h after the intravenous
      administration of VEGF165-aptamer-USPIO. The enhancement disappeared 6 h after
      administration of the probe. These results suggest the targeted imaging effect of
      VEGF165-aptamer-USPIO probe in vivo for VEGF165-expressing tumors. This is the
      first report of a targeted MRI molecular probe based on USPIO and VEGF165
      aptamer.

PMID- 24729583
TI  - SnS2 nanoplatelet@graphene nanocomposites as high-capacity anode materials for
      sodium-ion batteries.
AB  - Na-ion batteries have been attracting intensive investigations as a possible
      alternative to Li-ion batteries. Herein, we report the synthesis of SnS2
      nanoplatelet@graphene nanocomposites by using a morphology-controlled
      hydrothermal method. The as-prepared SnS2/graphene nanocomposites present a
      unique two-dimensional platelet-on-sheet nanoarchitecture, which has been
      identified by scanning and transmission electron microscopy. When applied as the
      anode material for Na-ion batteries, the SnS2/graphene nanosheets achieved a high
      reversible specific sodium-ion storage capacity of 725 mA h g(-1), stable
      cyclability, and an enhanced high-rate capability. The improved electrochemical
      performance for reversible sodium-ion storage could be ascribed to the
      synergistic effects of the SnS2 nanoplatelet/graphene nanosheets as an integrated
      hybrid nanoarchitecture, in which the graphene nanosheets provide electronic
      conductivity and cushion for the active SnS2 nanoplatelets during Na-ion
      insertion and extraction processes.

PMID- 24729584
TI  - Sequence analysis of a CTX-M-1 IncI1 plasmid found in Salmonella 4,5,12:i:-,
      Escherichia coli and Klebsiella pneumoniae on a UK pig farm.
AB  - OBJECTIVES: In 2009, CTX-M Enterobacteriaceae and Salmonella isolates were
      recovered from a UK pig farm, prompting studies into the dissemination of the
      resistance and to establish any relationships between the isolates. METHODS: PFGE
      was used to elucidate clonal relationships between isolates whilst plasmid
      profiling, restriction analysis, sequencing and PCR were used to characterize the
      CTX-M-harbouring plasmids. RESULTS: Escherichia coli, Klebsiella pneumoniae and
      Salmonella 4,5,12:i:- and Bovismorbificans resistant to cefotaxime (n = 65) were
      recovered and 63 were shown by PCR to harbour a group 1 CTX-M gene. The
      harbouring hosts were diverse, but the group 1 CTX-M plasmids were common. Three
      sequenced CTX-M plasmids from E. coli, K. pneumoniae and Salmonella enterica
      serotype 4,5,12:i:- were identical except for seven mutations and highly similar
      to IncI1 plasmid ColIb-P9. Two antimicrobial resistance regions were identified:
      one inserted upstream of yacABC harbouring ISCR2 transposases, sul2 and floR; and
      the other inserted within shfB of the pilV shufflon harbouring the ISEcp1
      transposase followed by blaCTX-M-1. CONCLUSIONS: These data suggest that an ST108
      IncI1 plasmid encoding a blaCTX-M-1 gene had disseminated across multiple genera
      on this farm, an example of horizontal gene transfer of the blaCTX-M-1 gene.

PMID- 24729585
TI  - Effect of antibiotic streamlining on patient outcome in pneumococcal bacteraemia.
AB  - OBJECTIVES: In blood culture-proven pneumococcal infections, streamlining
      empirical therapy to monotherapy with a penicillin is preferred in order to
      reduce the use of broad-spectrum antibiotics. However, adherence to this
      international recommendation is poor, and curiously it is unclear whether
      antibiotic streamlining may be harmful to individual patients. We investigated
      whether streamlining in bacteraemic pneumococcal infections is associated with
      mortality. METHODS: Adults admitted to two Dutch hospitals between 2001 and 2011
      with bacteraemic pneumococcal infections were retrospectively included. Detailed
      clinical data on patient characteristics, comorbidities and severity and outcome
      of disease were obtained in addition to data on antibiotic treatment. Those
      eligible for streamlining were selected for further analyses. RESULTS: In the
      45.8% of cases (126 of 275) where antibiotic treatment was streamlined, a lower
      mortality rate was observed (6.3% versus 15.4%, P = 0.021). The decision to
      streamline was only marginally explained by the 38 determinants accounted for.
      After correction for potential confounders, the OR for death while streamlining
      was 0.45 (95% CI: 0.18-1.11, P = 0.082) in all cases and 0.35 (95% CI: 0.12-0.99,
      P = 0.048) specifically in pneumonia cases. CONCLUSIONS: Our results suggest that
      streamlining in eligible pneumococcal bacteraemia cases is safe, irrespective of
      patient characteristics, severity of disease or empirical treatment regimen.

PMID- 24729587
TI  - In vivo Overhauser-enhanced MRI of proteolytic activity.
AB  - There is an increasing interest in developing novel imaging strategies for
      sensing proteolytic activities in intact organisms in vivo. Overhauser-enhanced
      MRI (OMRI) offers the possibility to reveal the proteolysis of nitroxide-labeled
      macromolecules thanks to a sharp decrease of the rotational correlation time of
      the nitroxide moiety upon cleavage. In this paper, this concept is illustrated in
      vivo at 0.2 T using nitroxide-labeled elastin orally administered in mice. In
      vitro, this elastin derivative was OMRI-visible and gave rise to high Overhauser
      enhancements (19-fold at 18 mm nitroxide) upon proteolysis by pancreatic porcine
      elastase. In vivo three-dimensional OMRI detection of proteolysis was carried
      out. A keyhole fully balanced steady-state free precession sequence was used,
      which allowed 3D OMRI acquisition within 20 s at 0.125 mm(3) resolution. About 30
      min after mouse gavage, proteolysis was detected in the duodenum, where
      Overhauser enhancements were 7.2 +/- 2.4 (n = 7) and was not observed in the
      stomach. Conversely, orally administered free nitroxides or pre-digested
      nitroxide-labeled elastin were detected in the mouse's stomach by OMRI. Combined
      with specific molecular probes, this Overhauser-enhanced MRI technique can be
      used to evaluate unregulated proteolytic activities in various models of
      experimental diseases and for drug testing.

PMID- 24729588
TI  - N-heterocyclic carbene-catalyzed enantioselective annulation of indolin-3-ones
      with bromoenals.
AB  - N-Heterocyclic carbene-catalyzed reactions of indolin-3-ones with 2-bromoenals
      opened an asymmetric access to 3,4-dihydropyrano[3,2-b]indol-2(5 H)-ones in good
      yields and with good to excellent enantioselectivities. This protocol tolerates a
      broad substrate scope. In addition, a possible mechanism for the annulation
      reaction is presented. 

PMID- 24729586
TI  - Secondary metabolism pathway polymorphisms and plasma efavirenz concentrations in
      HIV-infected adults with CYP2B6 slow metabolizer genotypes.
AB  - OBJECTIVES: Efavirenz is widely prescribed for HIV-1 infection, and CYP2B6
      polymorphisms 516G->T and 983T->C define efavirenz slow metabolizer genotypes. To
      identify genetic predictors of higher plasma efavirenz concentrations beyond
      these two common functional alleles, we characterized associations with mid
      dosing interval efavirenz concentrations in 84 HIV-infected adults, all carrying
      two copies of these major loss-of-function CYP2B6 alleles. METHODS: Study
      participants had been randomized to efavirenz-containing regimens in prospective
      clinical trials and had available plasma efavirenz assay data. Analyses focused
      on secondary metabolism pathway polymorphisms CYP2A6 -48T->G (rs28399433), UGT2B7
      735A->G (rs28365062) and UGT2B7 802T->C (rs7439366). Exploratory analyses also
      considered 196 polymorphisms and 8 copy number variants in 41 drug
      metabolism/transport genes. Mid-dosing interval efavirenz concentrations at
      steady-state were obtained >=8 h but <19 h post-dose. Linear regression was used
      to test for associations between polymorphisms and log-transformed efavirenz
      concentrations. RESULTS: Increased efavirenz concentrations were associated with
      CYP2A6 -48T->G in all subjects (P = 3.8 * 10(-4)) and in Black subjects (P =
      0.027) and White subjects (P = 0.0011) analysed separately; and with UGT2B7 735
      G/G homozygosity in all subjects (P = 0.006) and in Black subjects (P = 0.046)
      and White subjects (P = 0.062) analysed separately. In a multivariable model,
      CYP2A6 -48T->G and UGT2B7 735 G/G homozygosity remained significant (P < 0.05 for
      each). No additional polymorphisms or copy number variants were significantly
      associated with efavirenz concentrations. CONCLUSIONS: Among individuals with a
      CYP2B6 slow metabolizer genotype, CYP2A6 and possibly UGT2B7 polymorphisms
      contribute to even higher efavirenz concentrations.

PMID- 24729589
TI  - Pulsed feeding strategy is more favorable to medium-chain-length
      polyhydroxyalkanoates production from waste rapeseed oil.
AB  - This article presents the results of production and characterization of medium
      chain-length polyhydroxyalkanoates (mcl-PHAs) using Pseudomonas sp. Gl01. Studies
      have been carried out to find suitable feeding strategies for mcl-PHAs production
      and, for the first time, to investigate in-depth the properties of biopolyesters
      obtained under controlled conditions with waste rapeseed oil as a substrate. Up
      to 44% mcl-PHAs of cell dry weight was produced at 41 h of biofermentor culture
      by employing pulsed feeding of waste rapeseed oil. GC analysis showed a polymer
      composition with monomer length of C6 to C12 with C8 and C10 as the principal
      monomers. The monomeric structure of the extracted polyesters did not depend on
      the cultivation time and the feeding strategy. Molecular weight of the mcl-PHAs
      was found to be ranging from 57 to 154 kDa. Thermal analyses showed the obtained
      mcl-polyhydroxyalkanaotes to be semi-crystalline biopolymer with promising
      thermal stability, having a glass transition temperature of -38 to -50 degrees C.

PMID- 24729590
TI  - Protection from radon exposure at home and at work in the directive
      2013/59/Euratom.
AB  - In recent years, international organisations involved in radiation protection and
      public health have produced new guidance, recommendations and requirements aiming
      better protection from radon exposure. These organisations have often worked in
      close collaboration in order to facilitate the establishment of harmonised
      standards. This paper deals with such standards and specifically with the new
      European Council Directive of 5 December 2013 on basic safety standards for
      protection against the dangers arising from exposure to ionising radiation
      (2013/59/Euratom). This new Directive has established a harmonised framework for
      the protection against ionising radiations, including protection from radon
      exposure. Requirements for radon in workplace are much more tightening than in
      previous Directive, and exposures to radon in dwellings are regulated for the
      first time in a Directive. Radon-related articles of this Directive are presented
      and discussed in this paper, along with some comparisons with other relevant
      international standards. 

PMID- 24729591
TI  - Mechanisms and sources of radon entry in buildings constructed with modern
      technologies.
AB  - To investigate the influence of modern building construction technologies on the
      accumulation of radon indoor, 20 rooms in buildings constructed using mostly
      monolithic concrete or aerated concrete blocks have been studied. Dominance of
      the diffusion mechanism of radon entry in buildings constructed with modern
      technologies has been established. As a result of computer simulations it was
      found that the main contribution to the variability of radon concentration was
      made by changes in the ventilation rate. At a low ventilation rate (<0.2 h(-1))
      radon concentration above 200 Bq m(-3) can be observed for residential buildings.
      There is a need for the regulation of the radium-specific activity in building
      materials. According to the estimates of this study, the content of 226Ra in
      building materials should not exceed the value of 100 Bq kg(-1).

PMID- 24729592
TI  - On-body calibration and processing for a combination of two radio-frequency
      personal exposimeters.
AB  - Two radio-frequency personal exposimeters (PEMs) worn on both hips are calibrated
      on a subject in an anechoic chamber. The PEMs' response and crosstalk are
      determined for realistically polarised incident electric fields using this
      calibration. The 50 % confidence interval of the PEMs' response is reduced (2.6
      dB on average) when averaged over both PEMs. A significant crosstalk (up to a
      ratio of 1.2) is measured, indicating that PEM measurements can be obfuscated by
      crosstalk. Simultaneous measurements with two PEMs are carried out in Ghent,
      Belgium. The highest exposure is measured for Global System for Mobile
      Communication downlink (0.052 mW m(-2) on average), while the lowest exposure is
      found for Universal Mobile Telecommunications System uplink (0.061 MUW m(-2) on
      average). The authors recommend the use of a combination of multiple PEMs and,
      considering the multivariate data, to provide the mean vector and the covariance
      matrix next to the commonly listed univariate summary statistics, in future PEM
      studies. 

PMID- 24729593
TI  - Effects of water treatment and sample granularity on radiation sensitivity and
      stability of EPR signals in X-ray irradiated bone samples.
AB  - The article describes effects of sample conditions during its irradiation and
      electron paramagnetic resonance (EPR) measurements on the background (BG) and
      dosimetric EPR signals in bone. Intensity of the BG signal increased up to two to
      three times after crushing of bone to sub-millimetre grains. Immersion of samples
      in water caused about 50 % drop in intensity of the BG component followed by its
      regrowth in 1-2 months. Irradiation of bone samples produced an axial dosimetric
      EPR signal (radiation-induced signal) attributed to hydroxyapatite component of
      bone. This signal was stable and was not affected by water. In samples irradiated
      in dry conditions, EPR signal similar to the native BG was also generated by
      radiation. In samples irradiated in wet conditions, this BG-like component was
      initially much smaller than in bone irradiated as dry, but increased in time,
      reaching similar levels as in dry-irradiated samples. It is concluded that
      accuracy of EPR dosimetry in bones can be improved, if calibration of the samples
      is done by their irradiations in wet conditions. 

PMID- 24729595
TI  - SWOT analysis of the Czech Radon programme.
AB  - Since the early 1990s, the Czech Republic has been one of the countries that
      carry out a radon programme on its territory, with the aim of protecting people
      from unnecessary long-term exposure in their homes. Since that time, many
      achievements have been registered, and many unexpected difficulties have cropped
      up. This may be the right moment to take some time out to analyse the state of
      the programme and to determine the direction for its future development. An
      extended SWOT analysis can serve as a useful tool for this purpose. Originally,
      SWOT analyses were used exclusively by for-profit organisations aiming to
      evaluate their perspectives, develop strategies and make plans in order to
      achieve their objectives. More recently, it has been used in a wide range of
      decision-making situations when a desired end-state is to be defined. Here, an
      extended SWOT analysis is used to formulate possible beneficial strategies for
      advancing anti-radon policy in the Czech Republic. 

PMID- 24729594
TI  - Advances in a framework to compare bio-dosimetry methods for triage in large
      scale radiation events.
AB  - Planning and preparation for a large-scale nuclear event would be advanced by
      assessing the applicability of potentially available bio-dosimetry methods. Using
      an updated comparative framework the performance of six bio-dosimetry methods was
      compared for five different population sizes (100-1,000,000) and two rates for
      initiating processing of the marker (15 or 15,000 people per hour) with four
      additional time windows. These updated factors are extrinsic to the bio-dosimetry
      methods themselves but have direct effects on each method's ability to begin
      processing individuals and the size of the population that can be accommodated.
      The results indicate that increased population size, along with severely
      compromised infrastructure, increases the time needed to triage, which decreases
      the usefulness of many time intensive dosimetry methods. This framework and model
      for evaluating bio-dosimetry provides important information for policy-makers and
      response planners to facilitate evaluation of each method and should advance
      coordination of these methods into effective triage plans.

PMID- 24729596
TI  - Study on the influence of the B4C layer thickness on the neutron flux and energy
      distribution shape in multi-electrode ionisation chamber.
AB  - A model of a multi-electrode ionisation chamber, with polypropylene electrodes
      coated with a thin layer of B4C was created within Monte Carlo N-Particle
      Transport Code (MCNPX) and Fluktuierende Kaskade (FLUKA) codes. The influence of
      the layer thickness on neutron absorption in B4C and on the neutron spectra in
      the consecutive intra-electrode gas volumes has been studied using the MCNPX and
      FLUKA codes. The results will be used for designing the new type of the
      ionisation chamber. 

PMID- 24729602
TI  - QnrS1 structure-activity relationships.
AB  - OBJECTIVES: Loop B is important for low-level quinolone resistance conferred by
      Qnr proteins. The role of individual amino acids within QnrS1 loop B in quinolone
      resistance and gyrase protection was assessed. METHODS: qnrS1 and 11 qnrS1
      alleles with site-directed Ala mutations in loop B were expressed in Escherichia
      coli BL21(DE3) and proteins were purified by affinity chromatography.
      Ciprofloxacin MICs were determined with and without IPTG. Gyrase DNA supercoiling
      was measured with and without ciprofloxacin IC50 and with various concentrations
      of QnrS1 proteins. RESULTS: Wild-type QnrS1 and QnrS1 with Asn-110->Ala and Arg
      111->Ala substitutions increased the ciprofloxacin MIC 12-fold in BL21(DE3),
      although QnrS1 with Gln-107->Ala replacement increased it 2-fold more than wild
      type did. However, QnrS1 with Ala substitutions at His-106, Val-108, Ser-109, Met
      112, Tyr-113, Phe-114, Cys-115 and Ser-116 increased ciprofloxacin MIC 1.4- to 8
      fold less than wild-type QnrS1. Induction by 10-1000 MUM IPTG increased
      ciprofloxacin MICs for all mutants, reaching values similar to those for wild
      type. Purified wild-type and mutated proteins differed in protection of gyrase
      from ciprofloxacin action. Wild-type QnrS1 produced complete protection of gyrase
      supercoiling from ciprofloxacin (1.8 MUM) action at 0.05 nM and half protection
      at 0.5 pM, whereas QnrS1 with Ala replacements that conferred the least increase
      in ciprofloxacin MICs also required the highest QnrS1 concentrations for
      protection. CONCLUSIONS: Key individual residues in QnrS1 loop B affect
      ciprofloxacin resistance and gyrase protection from ciprofloxacin action,
      supporting the concept that loop B is key for interaction with gyrase necessary
      for quinolone resistance.

PMID- 24729603
TI  - The mother as most important risk factor for colonization of very low birth
      weight (VLBW) infants with extended-spectrum beta-lactamase-producing
      Enterobacteriaceae (ESBL-E).
AB  - OBJECTIVES: This study aimed to determine the prevalence of and risk factors for
      colonization with extended-spectrum beta-lactamase-producing Enterobacteriaceae
      (ESBL-E) and methicillin-resistant Staphylococcus aureus (MRSA) in very low birth
      weight (VLBW; <1500 g) infants and their mothers. METHODS: This investigation was
      conducted in the perinatal centre at the Charite Berlin between May 2012 and June
      2013. VLBW infants and their mothers were screened for colonization with ESBL-E
      and MRSA. Demographic and clinical data were obtained from the German nationwide
      surveillance system for nosocomial infections in VLBW infants (NEO-KISS) and used
      to perform univariate and multivariate analyses. RESULTS: Of 209 VLBW infants, 12
      (5.7%) were colonized with ESBL-E. Eighteen of 209 (8.6%) ESBL-E-tested neonates
      were related to an ESBL-E-positive mother. Univariate analysis, strain typing and
      multivariate analysis (OR 7.4, 95% CI 2.1-26.7, P = 0.002) identified an ESBL-E
      positive mother and maternal-neonatal transmission as a main source of
      colonization. The prevalence of MRSA was 2.3% (5 of 221) among VLBW infants. One
      of the 221 (0.5%) MRSA-tested neonates was related to an MRSA-positive mother. No
      risk factors for transmission of MRSA could be detected in this study.
      CONCLUSIONS: Our study demonstrated that maternal-neonatal transmission of ESBL-E
      from mother to child is an important risk factor for colonization of VLBW
      infants. As a consequence, routine ESBL-E screening of neonates and mothers
      should be considered as a means of reducing neonatal morbidity and mortality.

PMID- 24729604
TI  - HIV-1 drug mutations in children from northern Tanzania.
AB  - OBJECTIVES: In resource-limited settings, it is a challenge to get quality
      clinical specimens due to poor infrastructure for their collection,
      transportation, processing and storage. Using dried blood spots (DBS) might be an
      alternative to plasma for HIV-1 drug resistance testing in this setting. The
      objectives of this study were to determine mutations associated with
      antiretroviral resistance among children <18 months old born to HIV-1-infected
      mothers enrolled in prevention of mother-to-child transmission services in
      northern Tanzania. PATIENTS AND METHODS: Kilimanjaro Christian Medical Center
      (KCMC) Clinical Laboratory is the zonal centre for early infant diagnosis using
      DBS in northern Tanzania. DBS were collected from January 2011 to December 2012.
      Mothers were kept on triple therapy and single-dose nevirapine before pregnancy
      and during labour, respectively. Infants were given single-dose nevirapine and
      most of them were breastfed. Genotypic resistance was determined in those with a
      viral load of >400 copies/mL. RESULTS: Genotypic resistance mutations were
      detected in 13 of 46 children (28%). HIV-1 genotypes were A1 (n = 27), C (n =
      10), A/D (n = 4), D (n = 3) and CRF10_CD (n = 2). The median age was 12 weeks
      (IQR 6-28). The mean log10 viral load was 3.87 copies/mL (SD 0.995). All major
      mutations were detected in the reverse transcriptase gene and none in the
      protease gene region. The most frequent mutations were Y181C (n = 8) and K103N (n
      = 4), conferring resistance to non-nucleoside reverse transcriptase inhibitors.
      CONCLUSIONS: One-third of infants newly diagnosed with HIV in northern Tanzania
      harboured major drug resistance mutations to currently used antiretroviral
      regimens. These mutations were detected from DBS collected from the field and
      stored at room temperature. Surveillance of drug resistance among this population
      in resource-limited settings is warranted.

PMID- 24729605
TI  - Novel oral anti-influenza drug candidate AV5080.
AB  - OBJECTIVES: Development of a novel drug candidate with improved potency against
      influenza virus neuraminidase compared with currently available therapeutics, and
      high activity against oseltamivir-resistant viruses. METHODS: A number of
      synthetic compounds were evaluated for antiviral properties in vitro and in vivo.
      Three-dimensional molecular docking, assisted by a pharmacophore model, was
      applied to classify compounds within the series by their inhibitory potency.
      Compound stability in blood and in animal models was determined. Pharmacokinetic
      studies in dogs and rats after oral or intravenous administration were performed.
      RESULTS: A novel highly potent drug candidate [(3R,4R,5S)-5
      [(diaminomethylene)amino]-3-(1-ethylpropoxy)-4-[(fluoroacetyl)amino]cyclohex-1
      ene-1-carboxylic acid; AV5080] was synthesized and tested. AV5080 exhibited high
      activity against influenza virus neuraminidase in vitro, with IC(50) values of
      0.03 nM and 0.07 nM against the neuraminidase of A/Duck/Minnesota/1525/1981/H5N1
      and A/Perth/265/2009/H1N1 (wild-type), respectively. Notably, AV5080 was highly
      active against oseltamivir-resistant influenza viruses. CONCLUSIONS: Based on the
      results presented in this study, AV5080 is a promising novel oral drug candidate
      for the treatment of influenza, including oseltamivir-resistant types. Further
      pre-clinical development of AV5080 is warranted.

PMID- 24729606
TI  - The role of radiation therapy for resectable adenocarcinoma of the
      gastroesophageal junction.

PMID- 24729607
TI  - French FNCLCC/FFCD 9703 study.

PMID- 24729608
TI  - Smurf2 negatively modulates RIG-I-dependent antiviral response by targeting
      VISA/MAVS for ubiquitination and degradation.
AB  - VISA (also known as MAVS, Cardif, IPS-1) is the essential adaptor protein for
      virus-induced activation of IFN regulatory factors 3 and 7 and production of type
      I IFNs. Understanding the regulatory mechanisms for VISA will provide detailed
      insights into the positive or negative regulation of innate immune responses. In
      this study, we identified Smad ubiquitin regulatory factor (Smurf) 2, one of the
      Smad ubiquitin regulator factor proteins, as an important negative regulator of
      virus-triggered type I IFN signaling, which targets at the VISA level.
      Overexpression of Smurf2 inhibits virus-induced IFN-beta and IFN-stimulated
      response element activation. The E3 ligase defective mutant Smurf2/C716A loses
      the ability to suppress virus-induced type I IFN signaling, suggesting that the
      negative regulation is dependent on the ubiquitin E3 ligase activity of Smurf2.
      Further studies demonstrated that Smurf2 interacted with VISA and targeted VISA
      for K48-linked ubiquitination, which promoted the degradation of VISA.
      Consistently, knockout or knockdown of Smurf2 expression therefore promoted
      antiviral signaling, which was correlated with the increase in protein stability
      of VISA. Our findings suggest that Smurf2 is an important nonredundant negative
      regulator of virus-triggered type I IFN signaling by targeting VISA for K48
      linked ubiquitination and degradation. 

PMID- 24729609
TI  - Characterization of platelet-monocyte complexes in HIV-1-infected individuals:
      possible role in HIV-associated neuroinflammation.
AB  - HIV-1-associated neuroinflammation persists even with effective combined
      antiretroviral therapy, and it is associated with the presence of activated
      monocytes/macrophages within the CNS. To infiltrate the CNS, monocytes
      transmigrate across the selectively permeable blood-brain barrier, which is
      compromised during HIV-1 infection. Interestingly, platelet-derived excess
      soluble CD40 ligand found in the plasma and cerebrospinal fluid of HIV-1-infected
      individuals with cognitive impairment has previously been implicated in increased
      blood-brain barrier permeability. In this study we show that soluble CD40 ligand
      also promotes the formation of complexes between inflammatory monocytes and
      activated platelets (PMCs), which are detected by flow cytometry as monocytes
      that express excess of CD61, a platelet marker, and that these complexes are
      increased in individuals with HIV-1 infection. PMCs exhibit an enhanced ability
      to adhere to human brain microvascular endothelial cells as compared with
      monocytes alone, and they migrate across the transendothelial barrier. These
      complexes can be found marginalized in the lumen of postcapillary venules in
      postmortem brain tissue derived from cases of HIV-1-associated encephalitis. The
      extravasation of monocytes across the brain endothelium may exacerbate
      neuroinflammation, indicating that enhancing this event via platelet interaction
      may be a contributing factor in the development of cognitive impairment. Thus,
      dampening platelet activation, and in turn PMC formation, with antiplatelet
      agents may prove beneficial in developing adjunctive therapies for use in
      combination with combined antiretroviral therapy in an effort to reduce HIV-1
      associated neurologic deficit. 

PMID- 24729610
TI  - ATM increases activation-induced cytidine deaminase activity at downstream S
      regions during class-switch recombination.
AB  - Activation-induced cytidine deaminase (AID) initiates Ab class-switch
      recombination (CSR) in activated B cells resulting in exchanging the IgH C region
      and improved Ab effector function. During CSR, AID instigates DNA double-strand
      break (DSB) formation in switch (S) regions located upstream of C region genes.
      DSBs are necessary for CSR, but improper regulation of DSBs can lead to
      chromosomal translocations that can result in B cell lymphoma. The protein kinase
      ataxia telangiectasia mutated (ATM) is an important proximal regulator of the DNA
      damage response (DDR), and translocations involving S regions are increased in
      its absence. ATM phosphorylates H2AX, which recruits other DNA damage response
      (DDR) proteins, including mediator of DNA damage checkpoint 1 (Mdc1) and p53
      binding protein 1 (53BP1), to sites of DNA damage. As these DDR proteins all
      function to promote repair and recombination of DSBs during CSR, we examined
      whether mouse splenic B cells deficient in these proteins would show alterations
      in S region DSBs when undergoing CSR. We find that in atm(-/-) cells SMU DSBs are
      increased, whereas DSBs in downstream Sgamma regions are decreased. We also find
      that mutations in the unrearranged Sgamma3 segment are reduced in atm(-/-) cells.
      Our data suggest that ATM increases AID targeting and activity at downstream
      acceptor S regions during CSR and that in atm(-/-) cells SMU DSBs accumulate as
      they lack a recombination partner. 

PMID- 24729612
TI  - B7h triggering inhibits the migration of tumor cell lines.
AB  - Vascular endothelial cells (ECs) and several cancer cells express B7h, which is
      the ligand of the ICOS T cell costimulatory molecule. We have previously shown
      that B7h triggering via a soluble form of ICOS (ICOS-Fc) inhibits the adhesion of
      polymorphonuclear and tumor cell lines to HUVECs; thus, we suggested that ICOS-Fc
      may act as an anti-inflammatory and antitumor agent. Because cancer cell
      migration and angiogenesis are crucial for metastasis dissemination, the aim of
      this work was to evaluate the effect of ICOS-Fc on the migration of cancer cells
      and ECs. ICOS-Fc specifically inhibited the migration of HUVECs, human dermal
      lymphatic ECs, and the HT29, HCT116, PC-3, HepG2, JR8, and M14 tumor cell lines
      expressing high levels of B7h, whereas it was ineffective in the RPMI7932, PCF-2,
      LM, and BHT-101 cell lines expressing low levels of B7h. Furthermore, ICOS-Fc
      downmodulated hepatocyte growth factor facilitated the epithelial-to-mesenchymal
      transition in HepG2 cells. Moreover, ICOS-Fc downmodulated the phosphorylation of
      focal adhesion kinase and the expression of beta-Pix in both HUVECs and tumor
      cell lines. Finally, treatment with ICOS-Fc inhibited the development of lung
      metastases upon injection of NOD-SCID-IL2Rgammanull mice with CF-PAC1 cells, as
      well as C57BL/6 mice with B16-F10 cells. Therefore, the B7h-ICOS interaction may
      modulate the spread of cancer metastases, which suggests the novel use of ICOS-Fc
      as an immunomodulatory drug. However, in the B16-F10-metastasized lungs, ICOS-Fc
      also increased IL-17A/RORc and decreased IL-10/Foxp3 expression, which indicates
      that it also exerts positive effects on the antitumor immune response. 

PMID- 24729611
TI  - CD209a expression on dendritic cells is critical for the development of
      pathogenic Th17 cell responses in murine schistosomiasis.
AB  - In murine schistosomiasis, immunopathology and cytokine production in response to
      parasite eggs are uneven and strain dependent. CBA/J (CBA) mice develop severe
      hepatic granulomatous inflammation associated with prominent Th17 cell responses
      driven by dendritic cell (DC)-derived IL-1beta and IL-23. Such Th17 cells fail to
      develop in low-pathology C57BL/6 (BL/6) mice, and the reasons for these strain
      specific differences in APC reactivity to eggs remain unclear. We show by gene
      profiling that CBA DCs display an 18-fold higher expression of the C-type lectin
      receptor CD209a, a murine homolog of human DC-specific ICAM-3-grabbing
      nonintegrin, compared with BL/6 DCs. Higher CD209a expression was observed in CBA
      splenic and granuloma APC subpopulations, but only DCs induced Th17 cell
      differentiation in response to schistosome eggs. Gene silencing in CBA DCs and
      overexpression in BL/6 DCs demonstrated that CD209a is essential for egg-elicited
      IL-1beta and IL-23 production and subsequent Th17 cell development, which is
      associated with SRC, RAF-1, and ERK1/2 activation. These findings reveal a novel
      mechanism controlling the development of Th17 cell-mediated severe
      immunopathology in helminthic disease. 

PMID- 24729613
TI  - A silencer-proximal intronic region is required for sustained CD4 expression in
      postselection thymocytes.
AB  - It has been proposed that differential kinetics of CD4/CD8 coreceptors regulate
      fate choice of selected thymocytes. Sustained signals by interaction between MHC
      class II and TCR/CD4 is required for commitment to the CD4 helper lineage.
      Although prematurely terminated MHC-TCR/CD4 interaction in transgenic mouse
      models results in lineage redirection, it is unclear whether CD4 expression is
      actively maintained by endogenous cis-elements to facilitate prolonged signaling
      under physiological conditions. In this article, we show that sustained CD4
      expression in postselection thymocytes requires an intronic sequence containing
      an uncharacterized DNase I hypersensitivity (DHS) site located 3' to the
      silencer. Despite normal CD4 expression before selection, thymocytes lacking a
      1.5-kb sequence in intron 1 including the 0.4-kb silencer and the DHS, but not
      the 0.4-kb silencer alone, failed to maintain CD4 expression upon positive
      selection and are redirected to the CD8 lineage after MHC class II-restricted
      selection. Furthermore, CpG dinucleotides adjacent to the DHS are hypermethylated
      in CD8(+) T cells. These results indicate that the 1.5-kb cis-element is required
      in postselection thymocytes for helper lineage commitment, presumably mediating
      the maintenance of CD4 expression, and suggest that inactivation of the cis
      element by DNA methylation may contribute to epigenetic Cd4 silencing. 

PMID- 24729615
TI  - Naturally occurring human phosphorylcholine antibodies are predominantly products
      of affinity-matured B cells in the adult.
AB  - Phosphorylcholine (PC) is a classic T-independent Ag that is exposed on apoptotic
      cells, oxidized phospholipids, and bacterial polysaccharides. Experimental as
      well as epidemiological studies have over the past decade implicated Abs against
      PC (anti-PC) as anti-inflammatory and a strong protective factor in
      cardiovascular disease. Although clinically important, little is known about the
      development of anti-PC in humans. This study was conceived to dissect the human
      anti-PC repertoire and generate human mAbs. We designed a PC-specific probe to
      identify, isolate, and characterize PC-reactive B cells from 10 healthy
      individuals. The donors had all mounted somatically mutated Abs toward PC using a
      broad variety of Ig genes. PC-reactive B cells were primarily found in the IgM(+)
      memory subset, although significant numbers also were detected among naive,
      IgG(+), and CD27(+)CD43(+) B cells. Abs from these subsets were clonally related,
      suggesting a common origin. mAbs derived from the same donors exhibited
      equivalent or higher affinity for PC than the well-characterized murine T-15
      clone. These results provide novel insights into the cellular and molecular
      ontogeny of atheroprotective PC Abs, thereby offering new opportunities for Ab
      based therapeutic interventions. 

PMID- 24729614
TI  - Autoantibodies induced by chimeric cytokine-HIV envelope glycoprotein immunogens.
AB  - Cytokines are often used as adjuvants to increase the immunogenicity of vaccines
      because they can improve the immune response and/or direct it into a desired
      direction. As an alternative to codelivering Ags and cytokines separately, they
      can be fused into a composite protein, with the advantage that both moieties act
      on the same immune cells. The HIV-1 envelope glycoprotein (Env) spike, located on
      the outside of virus particles and the only relevant protein for the induction of
      neutralizing Abs, is poorly immunogenic. The induction of anti-Env Abs can be
      improved by coupling Env proteins to costimulatory molecules such as a
      proliferation inducing ligand (APRIL). In this study, we evaluated the
      immunogenicity of chimeric molecules containing uncleaved Env gp140 fused to the
      species-matched cytokines IL-21 or GM-CSF in rabbits and mice. Each cytokine was
      either fused to the C terminus of Env or embedded within Env at the position of
      the variable loops 1 and 2. The cytokine components of the chimeric Env-GM-CSF
      and Env-IL-21 molecules were functional in vitro, but none of the Env-cytokine
      fusion proteins resulted in improved Ab responses in vivo. Both the Env-GM-CSF
      and the Env-IL-21 molecules induced strong anticytokine Ab responses in both test
      species. These autoimmune responses were independent of the location of the
      cytokine in the chimeric Env molecules in that they were induced by cytokines
      inserted within the variable loops 1 and 2 of Env or fused to its C terminus. The
      induction of undesired autoimmune responses should be considered when using
      cytokines as costimulatory molecules in fusion proteins. 

PMID- 24729616
TI  - Phagocytosis of Staphylococcus aureus by human neutrophils prevents macrophage
      efferocytosis and induces programmed necrosis.
AB  - Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) pose a
      significant threat to human health. Polymorphonuclear leukocytes (PMN) are the
      first responders during staphylococcal infection, but 15-50% of the initial
      ingested inoculum survives within the PMN phagosome and likely contributes
      directly or indirectly to disease pathogenesis. We hypothesize that surviving
      intracellular CA-MRSA undermine effective phagocyte-mediated defense by causing a
      decrease in macrophage uptake of PMN containing viable S. aureus and by promoting
      PMN lysis. In support of this hypothesis, PMN harboring viable CA-MRSA strain
      USA300 (PMN-SA) upregulated the "don't eat me" signal CD47, remained bound to the
      surface, and were inefficiently ingested by macrophages. In addition, coculture
      with PMN-SA altered the macrophage phenotype. Compared to macrophages fed USA300
      alone, macrophages challenged with PMN-SA produced more IL-8 and less IL-1
      receptor antagonist, TNF-alpha, activated caspase-1, and IL-1beta. Although they
      exhibited some features of apoptosis within 3 h following ingestion of S. aureus,
      including phosphatidylserine exposure and mitochondrial membrane depolarization,
      PMN-SA had sustained levels of proliferating cell nuclear Ag expression, absence
      of caspase activation, and underwent lysis within 6 h following phagocytosis. PMN
      lysis was dependent on receptor-interacting protein 1, suggesting that PMN-SA
      underwent programmed necrosis or necroptosis. These data are the first
      demonstration, to our knowledge, that bacteria can promote sustained expression
      of proliferating cell nuclear Ag and that human PMN undergo necroptosis.
      Together, these findings demonstrate that S. aureus surviving within PMN
      undermine the innate immune response and may provide insight into the
      pathogenesis of S. aureus disease. 

PMID- 24729618
TI  - Leukotriene B4 modulates P2X7 receptor-mediated Leishmania amazonensis
      elimination in murine macrophages.
AB  - ATP is an important signaling molecule in the immune system, and it is able to
      bind the P2X7 purinergic receptor. Recently, our group showed that ATP-treated
      macrophages eliminate Leishmania amazonensis. It has been reported that
      leukotriene B4 (LTB4) reduces the parasitic load of infected macrophages.
      Additionally, it has been demonstrated that the P2X7 receptor can induce PLA2
      activation and arachidonic acid mobilization. Based on these findings, we
      investigated whether LTB4 is produced upon P2X7 receptor activation and examined
      whether LTB4 modulates parasite elimination. Using macrophages lacking the P2X7
      receptor, we observed that ATP was not able to reduce L. amazonensis load. This
      result suggests a role of the P2X7 purinergic receptor in parasite elimination.
      In addition, ATP was sufficient to induce LTB4 release from infected control
      macrophages but not from macrophages lacking the P2X7 receptor. Moreover, we
      found that ATP failed to decrease the parasitic load in 5-lipoxygenase (LO)
      deficient macrophages. Treatment with the 5-LO inhibitor AA861 also impairs the
      ATP effect on parasitic loads. Furthermore, macrophages from 5-LO knockout mice
      eliminated L. amazonensis in the presence of exogenous LTB4, and macrophages
      obtained from P2X7 receptor knockout mice eliminated L. amazonensis when
      incubated with ionomycin. Finally, we demonstrated that in the presence of
      CP105696, an antagonist for LTB4 high-affinity receptor, ATP was not able to
      reduce parasitic load. These results indicate that P2X7 receptor activation leads
      to LTB4 formation, which is required for L. amazonensis elimination. 

PMID- 24729617
TI  - A humanized antibody that regulates the alternative pathway convertase: potential
      for therapy of renal disease associated with nephritic factors.
AB  - Dysregulation of the complement alternative pathway can cause disease in various
      organs that may be life-threatening. Severe alternative pathway dysregulation can
      be triggered by autoantibodies to the C3 convertase, termed nephritic factors,
      which cause pathological stabilization of the convertase enzyme and confer
      resistance to innate control mechanisms; unregulated complement consumption
      followed by deposition of C3 fragments in tissues ensues. The mAb, 3E7, and its
      humanized derivative, H17, have been shown previously to specifically bind
      activated C3 and prevent binding of both the activating protein, factor B, and
      the inhibitor, factor H, which are opposite effects that complicate its potential
      for therapy. Using ligand binding assays, functional assays, and electron
      microscopy, we show that these Abs bind C3b via a site that overlaps the binding
      site on C3 for the Ba domain within factor B, thereby blocking an interaction
      essential for convertase formation. Both Abs also bind the preformed convertase,
      C3bBb, and provide powerful inhibition of complement activation by preventing
      cleavage of C3. Critically, the Abs also bound and inhibited C3 cleavage by the
      nephritic factor-stabilized convertase. We suggest that by preventing enzyme
      formation and/or cleavage of C3 to its active downstream fragments, H17 may be an
      effective therapy for conditions caused by severe dysregulation of the C3
      convertase and, in particular, those that involve nephritic factors, such as
      dense deposit disease. 

PMID- 24729620
TI  - Tyk2-dependent bystander activation of conventional and nonconventional Th1 cell
      subsets contributes to innate host defense against Listeria monocytogenes
      infection.
AB  - IL-12, which is produced in response to intracellular bacteria, such as Listeria
      monocytogenes, promotes the development of pathogen-specific Th1 cells that play
      an important role in host defense. However, it has also been known that
      CD44(high) memory-phenotype CD4 T cells with Th1 functions naturally occur in
      naive mice, and that lymphopenia-induced proliferation of naive CD4 T cells
      generates memory-phenotype CD4 T cells with Th1 functions, although their
      differentiation mechanism and contribution to host defense are unclear. In this
      study, we analyzed the development and the functions of the different subsets of
      Th1 cells by using mice lacking tyrosine kinase 2 (Tyk2), a member of the Janus
      kinase family critically involved in IL-12 signaling. In contrast with the case
      of conventional Ag-specific Th1 cells, the development of naturally occurring Th1
      cells was not impaired in Tyk2-deficient mice. In addition, Th1 cells were
      normally generated from Tyk2-deficient naive CD4 T cells via lymphopenia-induced
      proliferation. Nevertheless, all these Th1 subsets, including conventional Ag
      induced Th1 cells, produced IFN-gamma in response to IL-12 in a Tyk2-dependent
      manner. Importantly, such Tyk2-dependent bystander IFN-gamma production of any
      Th1 subsets conferred early protection against L. monocytogenes infection. Thus,
      Tyk2-mediated IL-12 signaling is differentially required for the development of
      different Th1 cell subsets but similarly induces their bystander IFN-gamma
      production, which contributes to innate host defense against infection with
      intracellular bacteria. 

PMID- 24729619
TI  - Polyinosinic-polycytidylic acid has therapeutic effects against cerebral
      ischemia/reperfusion injury through the downregulation of TLR4 signaling via
      TLR3.
AB  - Recent reports have shown that preconditioning with the TLR3 ligand polyinosinic
      polycytidylic acid (poly(I:C)) protects against cerebral ischemia/reperfusion
      (I/R) injury. However, it is unclear whether poly(I:C) treatment after cerebral
      I/R injury is also effective. We used mouse/rat middle cerebral artery occlusion
      and cell oxygen-glucose deprivation models to evaluate the therapeutic effects
      and mechanisms of poly(I:C) treatment. Poly(I:C) was i.p. injected 3 h after
      ischemia (treatment group). Cerebral infarct volumes and brain edemas were
      significantly reduced, and neurologic scores were significantly increased. TNF
      alpha and IL-1beta levels were markedly decreased, whereas IFN-beta levels were
      greatly increased, in the ischemic brain tissues, cerebral spinal fluid, and
      serum. Injuries to hippocampal neurons and mitochondria were greatly reduced. The
      numbers of TUNEL-positive and Fluoro-Jade B(+) cells also decreased significantly
      in the ischemic brain tissues. Poly(I:C) treatment increased the levels of Hsp27,
      Hsp70, and Bcl2 and decreased the level of Bax in the ischemic brain tissues.
      Moreover, poly(I:C) treatment attenuated the levels of TNF-alpha and IL-1beta in
      serum and cerebral spinal fluid of mice stimulated by LPS. However, the
      protective effects of poly(I:C) against cerebral ischemia were abolished in TLR3(
      /-) and TLR4(-/-)mice. Poly(I:C) downregulated TLR4 signaling via TLR3. Poly(I:C)
      treatment exhibited obvious protective effects 14 d after ischemia and was also
      effective in the rat permanent middle cerebral artery occlusion model. The
      results suggest that poly(I:C) exerts therapeutic effects against cerebral I/R
      injury through the downregulation of TLR4 signaling via TLR3. Poly(I:C) is a
      promising new drug candidate for the treatment of cerebral infarcts. 

PMID- 24729621
TI  - Divergent CD4+ T memory stem cell dynamics in pathogenic and nonpathogenic simian
      immunodeficiency virus infections.
AB  - Recent studies have identified a subset of memory T cells with stem cell-like
      properties (T(SCM)) that include increased longevity and proliferative potential.
      In this study, we examined the dynamics of CD4(+) T(SCM) during pathogenic SIV
      infection of rhesus macaques (RM) and nonpathogenic SIV infection of sooty
      mangabeys (SM). Whereas SIV-infected RM show selective numeric preservation of
      CD4(+) T(SCM), SIV infection induced a complex perturbation of these cells
      defined by depletion of CD4(+)CCR5(+) T(SCM), increased rates of CD4(+) T(SCM)
      proliferation, and high levels of direct virus infection. The increased rates of
      CD4(+) T(SCM) proliferation in SIV-infected RM correlated inversely with the
      levels of central memory CD4(+) T cells. In contrast, nonpathogenic SIV infection
      of SM evidenced preservation of both CD4(+) T(SCM) and CD4(+) central memory T
      cells, with normal levels of CD4(+) T(SCM) proliferation, and lack of selective
      depletion of CD4(+)CCR5(+) T(SCM). Importantly, SIV DNA was below the detectable
      limit in CD4(+) T(SCM) from 8 of 10 SIV-infected SM. We propose that increased
      proliferation and infection of CD4(+) T(SCM) may contribute to the pathogenesis
      of SIV infection in RM.

PMID- 24729622
TI  - Negative human papillomavirus status and excessive alcohol consumption are
      significant risk factors for second primary malignancies in Japanese patients
      with oropharyngeal carcinoma.
AB  - OBJECTIVE: To determine the clinical significance of human papillomavirus
      subclinical infection in patients with oropharyngeal squamous cell carcinoma in
      Japan. METHODS: Over a 9-year period, a retrospective case comparison study of
      the pathology database was conducted at the University of Tokyo to identify
      samples of oropharyngeal squamous cell carcinoma. We performed in situ
      hybridization for human papillomavirus-DNA to identify subclinical human
      papillomavirus infections among patients with oropharyngeal squamous cell
      carcinoma. Second primary malignancies were classified as synchronous, if
      identified within 6 months of the diagnosis of the first tumor, or metachronous,
      if identified after this 6-month period. Univariate and multivariate analyses
      using logistic stepwise regression models were performed to identify factors
      associated with synchronous and metachronous second primary malignancy. RESULTS:
      Of the 150 patients with oropharyngeal squamous cell carcinoma, 14% (21/150) and
      20.7% (31/150) developed synchronous and metachronous second primary
      malignancies, respectively. Esophageal carcinoma was the most frequent second
      primary malignancy (10/21 for synchronous and 10/31 for metachronous second
      primary malignancies). The prevalence of oropharyngeal squamous cell carcinoma
      positive for human papillomavirus was 31% (47/150). Multivariate analysis
      identified alcohol consumption as a significant unfavorable risk factor for the
      occurrence of synchronous second primary malignancy, and either a human
      papillomavirus-negative status or N0 classification was a significant unfavorable
      risk factor for the occurrence of metachronous second primary malignancy.
      CONCLUSIONS: Evaluation of the human papillomavirus status may help identify
      patients at risk for metachronous second primary malignancy. Upper
      gastrointestinal endoscopy is very important in the diagnosis of oropharyngeal
      squamous cell carcinoma among heavy drinkers in Japan.

PMID- 24729623
TI  - Japanese structure survey of high-precision radiotherapy in 2012 based on
      institutional questionnaire about the patterns of care.
AB  - OBJECTIVE: The purpose of this study was to clarify operational situations,
      treatment planning and processes, quality assurance and quality control with
      relevance to stereotactic radiotherapy, intensity-modulated radiotherapy and
      image-guided radiotherapy in Japan. METHODS: We adopted 109 items as the quality
      indicators of high-precision radiotherapy to prepare a questionnaire. In April
      2012, we started to publicly open the questionnaire on the website, requesting
      every institution with radiotherapy machines for response. The response ratio was
      62.1% (490 out of 789 institutions responded). RESULTS: Two or more radiotherapy
      technologists per linear accelerator managed linear accelerator operation in ~90%
      of the responded institutions while medical physicists/radiotherapy quality
      managers were engaged in the operation in only 64.9% of the institutions.
      Radiotherapy certified nurses also worked in only 18.4% of the institutions. The
      ratios of the institutions equipped for stereotactic radiotherapy of lung tumor,
      intensity-modulated radiotherapy and image-guided radiotherapy were 43.3, 32.6
      and 46.8%, respectively. In intensity-modulated radiotherapy planning, radiation
      oncologists were usually responsible for delineation while medical
      physicists/radiotherapy quality managers or radiotherapy technologists set up
      beam in 33.3% of the institutions. The median time required for quality assurance
      of intensity-modulated radiotherapy at any site of brain, head and neck and
      prostate was 4 h. Intensity-modulated radiotherapy quality assurance activity had
      to be started after clinical hours in >60% of the institutions. CONCLUSIONS: This
      study clarified one major issue in the current high-precision radiotherapy in
      Japan. A manpower shortage should be corrected for high-precision radiotherapy,
      especially in the area relevant to quality assurance/quality control.

PMID- 24729625
TI  - Haplotypes of the inducible nitric oxide synthase gene are strongly associated
      with exhaled nitric oxide levels in adults: a population-based study.
AB  - BACKGROUND: Previous genetic association studies have reported evidence for
      association of single-nucleotide polymorphisms (SNPs) in the NOS2 gene, encoding
      inducible nitric oxide synthase (iNOS), to variation in levels of fractional
      exhaled nitric oxide (FENO) in children and adults. In this study, we evaluated
      10 SNPs in the region of chromosome 17 from 26.07 Mb to 26.13 Mb to further
      understand the contribution of NOS2 to variation in levels of FENO. METHODS: In a
      cohort of 5912 adults 25-75 years of age, we investigated the relationship
      between NOS2 haplotypes and FENO, and effect modification by asthma. RESULTS:
      Seven common (frequency >=5%) haplotypes (H1-H7) were inferred from all possible
      haplotype combinations. One haplotype (H3) was significantly associated with
      lower levels of FENO: -5.8% (95% CI -9.8 to -1.7; p=0.006) compared with the most
      common baseline haplotype H1. Two haplotypes (H5 and H6) were significantly
      associated with higher levels of FENO: +10.7% (95% CI 5.0 to 16.7; p=0.0002) and
      +14.9% (95% CI 10.6 to 19.3; p=7.8*10(-13)), respectively. The effect of
      haplotype H3 was mainly seen in subjects with asthma (-21.6% (95% CI -33.5 to 
      5.9)) and was not significant in subjects without asthma (-4.2% (95% CI -8.4 to
      0.2)). The p value for interaction between H3 and asthma status was 0.004.
      CONCLUSIONS: Our findings suggest that several common haplotypes in the NOS2 gene
      contribute to variation in FENO in adults. We also saw some evidence of effect
      modification by asthma status on haplotype H3.

PMID- 24729624
TI  - RNA binding protein HuR regulates the expression of ABCA1.
AB  - ABCA1 is a major regulator of cellular cholesterol efflux and plasma HDL
      biogenesis. Even though the transcriptional activation of ABCA1 is well
      established, the posttranscriptional regulation of ABCA1 expression is poorly
      understood. Here, we investigate the potential contribution of the RNA binding
      protein (RBP) human antigen R (HuR) on the posttranscriptional regulation of
      ABCA1 expression. RNA immunoprecipitation assays demonstrate a direct interaction
      between HuR and ABCA1 mRNA. We found that HuR binds to the 3' untranslated region
      of ABCA1 and increases ABCA1 translation, while HuR silencing reduces ABCA1
      expression and cholesterol efflux to ApoA1 in human hepatic (Huh-7) and monocytic
      (THP-1) cells. Interestingly, cellular cholesterol levels regulate the
      expression, intracellular localization, and interaction between HuR and ABCA1
      mRNA. Finally, we found that HuR expression was significantly increased in
      macrophages from human atherosclerotic plaques, suggesting an important role for
      this RBP in controlling macrophage cholesterol metabolism in vivo. In summary, we
      have identified HuR as a novel posttranscriptional regulator of ABCA1 expression
      and cellular cholesterol homeostasis, thereby opening new avenues for increasing
      cholesterol efflux from atherosclerotic foam macrophages and raising circulat-ing
      HDL cholesterol levels.

PMID- 24729626
TI  - The mind's eye.

PMID- 24729627
TI  - Socioeconomic deprivation and provision of acute and long-term care after stroke:
      the South London Stroke Register cohort study.
AB  - BACKGROUND AND AIMS: Socioeconomic deprivation (SED) is associated with increased
      mortality after stroke, however, its associations with stroke care remains
      uncertain. We assessed the SED impacts on acute and long-term stroke care, and
      examined their ethnic differences and secular trends. METHODS: We used data from
      4202 patients with first-ever stroke (mean age 70.1 years, 50.4% male, 20.4%
      black), collected by a population-based stroke register in South London, England
      from 1995 to 2010. Carstairs deprivation score was measured for each patient,
      taking the 1st as the least deprived and the 2nd to 5th quintiles as SED, and was
      related to 20 indicators of care in multivariate logistic regression models.
      RESULTS: Patients with SED had 29% and 35% statistically significant reductions
      in odds of being admitted to hospital and having swallow tests, respectively. The
      multivariate adjusted odds ratio (OR) for receiving five indicators of acute
      stroke care was 0.81 (95% CI 0.72 to 0.92). It was 0.76 (0.58 to 0.99) in black
      patients and 0.82 (0.71 to 0.96) in white patients; and 0.70 (0.58 to 0.84) in
      patients with stroke occurring before 2001 and 0.89 (0.75 to 1.05) since 2001.
      SED was further associated with receipt of some stroke care during 5 years of
      follow-up, including atrial fibrillation medication (0.63, 0.48 to 0.83), and in
      black patients physiotherapy and occupational therapy (0.32, 0.11 to 0.92).
      CONCLUSIONS: Stroke healthcare inequalities in England exist for some important
      indicators, although overall it has improved over time. The impact of SED may be
      stronger in black patients than in white patients. Further efforts are required
      to achieve stroke care equality.

PMID- 24729628
TI  - On a multiphase multicomponent model of biofilm growth.
AB  - Biofilms are formed when free-floating bacteria attach to a surface and secrete
      polysaccharide to form an extracellular polymeric matrix (EPS). A general model
      of biofilm growth needs to include the bacteria, the EPS, and the solvent within
      the biofilm region Omega(t), and the solvent in the surrounding region D(t). The
      interface between the two regions, Gamma(t), is a free boundary. In this paper,
      we consider a mathematical model, which consists of a Stokes equation for the EPS
      with bacteria attached to it, and a Stokes equation for the solvent in Omega(t)
      and a different one for the solvent in D(t). The volume fraction of the EPS is
      another unknown satisfying a reaction-diffusion equation. The entire system is
      coupled nonlinearly within Omega(t), and across the free surface Gamma(t). We
      prove the existence and uniqueness of solution, with a smooth surface Gamma(t),
      for a small time interval.

PMID- 24729629
TI  - Improving Reproducibility of Lab-on-a-Chip Sensor with Bismuth Working Electrode
      for Determining Zn in Serum by Anodic Stripping Voltammetry.
AB  - This work reports on the continuing development of a lab-on-a-chip
      electrochemical sensor for determination of zinc in blood serum using square wave
      anodic stripping voltammetry. The microscale sensor consists of a three electrode
      system, including an environmentally friendly bismuth working electrode, an
      integrated silver/silver chloride reference electrode, and a gold auxiliary
      electrode. The sensor demonstrates a linear response in 0.1 M acetate buffer at
      pH 6 for zinc concentrations in the 1-30 MUM range. By optimizing bismuth film
      deposition and better control of the fabrication process, repeatability of the
      sensor was improved, reducing variability from 42% to <2%. Through optimization
      of electrolyte and stripping voltammetry parameters, limit of detection was
      greatly improved to 60 nM. The optimized sensor was also able to measure zinc in
      the extracted blood serum. Ultimately, with integrated sample preparation, the
      sensor will permit rapid (min) measurements of zinc from a sub-mL sample (a few
      drops of blood) for clinical applications.

PMID- 24729630
TI  - Contact-coupled impact of slender rods: analysis and experimental validation.
AB  - To validate models of contact mechanics in low speed structural impact, slender
      rods were impacted in a drop tower, and measurements of the contact and vibration
      were compared to analytical and finite element (FE) models. The contact area was
      recorded using a novel thin-film transfer technique, and the contact duration was
      measured using electrical continuity. Strain gages recorded the vibratory strain
      in one rod, and a laser Doppler vibrometer measured speed. The experiment was
      modeled analytically on a one-dimensional spatial domain using a quasi-static
      Hertzian contact law and a system of delay differential equations. The three
      dimensional FE model used hexahedral elements, a penalty contact algorithm, and
      explicit time integration. A small submodel taken from the initial global FE
      model economically refined the analysis in the small contact region. Measured
      contact areas were within 6% of both models' predictions, peak speeds within 2%,
      cyclic strains within 12 MUepsilon (RMS value), and contact durations within 2
      MUs. The global FE model and the measurements revealed small disturbances, not
      predicted by the analytical model, believed to be caused by interactions of the
      non-planar stress wavefront with the rod's ends. The accuracy of the predictions
      for this simple test, as well as the versatility of the diagnostic tools,
      validates the theoretical and computational models, corroborates instrument
      calibration, and establishes confidence that the same methods may be used in
      experimental and computational study of contact mechanics during impact of more
      complicated structures. Recommendations are made for applying the methods to a
      particular biomechanical problem: the edge-loading of a loose prosthetic hip
      joint which can lead to premature wear and prosthesis failure.

PMID- 24729631
TI  - Quantitative Measurement of Dissection Resistance in Intimal and Medial Layers of
      Human Coronary Arteries.
AB  - The left anterior descending (LAD) coronary artery is the most frequently
      involved vessel in coronary artery dissection, a cause of acute coronary syndrome
      or sudden cardiac death. The biomechanical mechanisms underlying arterial
      dissection are not well understood. This study investigated the dissection
      properties of LAD specimens harvested from explanted hearts at the time of
      cardiac transplantation, from patients with primary dilated cardiomyopathy
      (n=12). Using a previously validated approach uniquely modified for these human
      LAD specimens, we quantified the local energy release rate, G, within different
      arterial layers during experimental dissection events (tissue tearing). Results
      show that the mean values of G during arterial dissection within the intima and
      within the media in human LADs are 20.7+/-16.5 J/m2 and 10.3+/-5.0 J/m2,
      respectively. The difference in dissection resistance between tearing events
      occurring within the intima and within the media is statistically significant.
      Our data fall in the same order of magnitude as most previous measurements of
      adhesive strength in other human arteries, with the differences in measured
      values of G within the layers most likely due to histologically observed
      differences in the structure and composition of arterial layers.

PMID- 24729632
TI  - Do People Who Believe in God Report More Meaning in Their Lives? The Existential
      Effects of Belief.
AB  - I conduct the first large-N study explicitly exploring the association between
      belief in God and sense of purpose in life. This relationship, while often
      discussed informally, has received little empirical attention. Here I use the
      General Social Survey to investigate how form of and confidence in belief in God
      is related to sense of purpose in life, as measured by a Likert item level of
      agreement with the statement "In my opinion, life does not serve any purpose."
      Using logistic regression analysis, I find that those who indicate that they are
      confident in God's existence report a higher sense of purpose compared to
      nonbelievers, believers in a higher power, and those who believe but occasionally
      doubt.

PMID- 24729633
TI  - Characterization and quantification of groundwater sulfate sources at a mining
      site in an arid climate: The Monument Valley site in Arizona, USA.
AB  - The Monument Valley site, a former uranium mining site located in the state of
      Arizona in the Southwest USA, has high concentrations of sulfate in groundwater.
      Stable isotope analysis of S and O for sulfate, in combination with geochemical
      and hydrogeological data, was used to characterize the sources and fate of
      sulfate. The results indicate the existence of two discrete sources of sulfate
      (in excess of baseline levels): sulfuric acid released during ore processing and
      sulfate generated via sulfide-mineral oxidation. The contributions of the sources
      are related to spatial distributions of sulfate in the plume through analysis of
      groundwater travel times. Quantification of the sources using two isotope
      analysis methods yielded similar results. The results indicate that sulfuric acid
      served as the primary source (mean = 427 mg/L, 74%), with sulfide-mineral
      oxidation providing a smaller contribution (mean = 147 mg/L, 26%). It appears
      that the major contribution to the sulfide-mineral oxidation component originates
      from oxidation of sulfide minerals in exposed bedrock residing in the primary
      recharge zone of the local aquifer, which provides an elevated sulfate background
      for groundwater. Conversely, the oxidation of sulfide minerals associated with
      the mine tailings appears to provide a relatively minor contribution (~8% of the
      overall total). Interestingly, it appears that sulfuric acid served as a
      sustained source of sulfate for approximately 40 years. This may be related to
      the accumulation of sulfate salts (formed after neutralization and disposal of
      the sulfuric acid) in the source zone due to the arid climate of the site.
      Contrary to the typical assumption applied at many mining sites that sulfide
      mineral oxidation is the primary source of sulfate, these sulfate salts are
      hypothesized to be the primary source for this site.

PMID- 24729634
TI  - Hearing versus Listening: Attention to Speech and Its Role in Language
      Acquisition in Deaf Infants with Cochlear Implants.
AB  - The advent of cochlear implantation has provided thousands of deaf infants and
      children access to speech and the opportunity to learn spoken language. Whether
      or not deaf infants successfully learn spoken language after implantation may
      depend in part on the extent to which they listen to speech rather than just hear
      it. We explore this question by examining the role that attention to speech plays
      in early language development according to a prominent model of infant speech
      perception - Jusczyk's WRAPSA model - and by reviewing the kinds of speech input
      that maintains normal-hearing infants' attention. We then review recent findings
      suggesting that cochlear-implanted infants' attention to speech is reduced
      compared to normal-hearing infants and that speech input to these infants differs
      from input to infants with normal hearing. Finally, we discuss possible roles
      attention to speech may play on deaf children's language acquisition after
      cochlear implantation in light of these findings and predictions from Jusczyk's
      WRAPSA model.

PMID- 24729635
TI  - Aromatic interactions impact ligand binding and function at serotonin 5-HT2C G
      protein-coupled receptors: Receptor homology modeling, ligand docking, and
      molecular dynamics results validated by experimental studies.
AB  - The serotonin (5-hydroxytryptamine, 5-HT) 5-HT2 G protein-coupled receptor (GPCR)
      family consists of types 2A, 2B, and 2C that share ~75% transmembrane (TM)
      sequence identity. Agonists for 5-HT2C receptors are under development for
      psychoses, whereas, at 5-HT2A receptors, antipsychotic effects are associated
      with antagonists-in fact, 5-HT2A agonists can cause hallucinations and 5-HT2B
      agonists cause cardiotoxicity. It is known that 5-HT2A TM6 residues W6.48, F6.51,
      and F6.52 impact ligand binding and function, however, ligand interactions with
      these residues at the 5-HT2C receptor has not been reported. To predict and
      validate molecular determinants for 5-HT2C-specific activation, results from
      receptor homology modeling, ligand docking, and molecular dynamics (MD)
      simulation studies were compared with experimental results for ligand binding and
      function at wild type and W6.48A, F6.51A, and F6.52A point-mutated 5-HT2C
      receptors.

PMID- 24729636
TI  - Moments and Root-Mean-Square Error of the Bayesian MMSE Estimator of
      Classification Error in the Gaussian Model.
AB  - The most important aspect of any classifier is its error rate, because this
      quantifies its predictive capacity. Thus, the accuracy of error estimation is
      critical. Error estimation is problematic in small-sample classifier design
      because the error must be estimated using the same data from which the classifier
      has been designed. Use of prior knowledge, in the form of a prior distribution on
      an uncertainty class of feature-label distributions to which the true, but
      unknown, feature-distribution belongs, can facilitate accurate error estimation
      (in the mean-square sense) in circumstances where accurate completely model-free
      error estimation is impossible. This paper provides analytic asymptotically exact
      finite-sample approximations for various performance metrics of the resulting
      Bayesian Minimum Mean-Square-Error (MMSE) error estimator in the case of linear
      discriminant analysis (LDA) in the multivariate Gaussian model. These performance
      metrics include the first, second, and cross moments of the Bayesian MMSE error
      estimator with the true error of LDA, and therefore, the Root-Mean-Square (RMS)
      error of the estimator. We lay down the theoretical groundwork for Kolmogorov
      double-asymptotics in a Bayesian setting, which enables us to derive asymptotic
      expressions of the desired performance metrics. From these we produce analytic
      finite-sample approximations and demonstrate their accuracy via numerical
      examples. Various examples illustrate the behavior of these approximations and
      their use in determining the necessary sample size to achieve a desired RMS. The
      Supplementary Material contains derivations for some equations and added figures.

PMID- 24729637
TI  - Hierarchical longitudinal models of relationships in social networks.
AB  - Motivated by the need to understand the dynamics of relationship formation and
      dissolution over time in real-world social networks we develop a new longitudinal
      model for transitions in the relationship status of pairs of individuals
      ("dyads"). We first specify a model for the relationship status of a single dyad
      and then extend it to account for important inter-dyad dependencies (e.g.,
      transitivity - "a friend of a friend is a friend") and heterogeneity. Model
      parameters are estimated using Bayesian analysis implemented via Markov chain
      Monte Carlo. We use the model to perform novel analyses of two diverse
      longitudinal friendship networks: an excerpt of the Teenage Friends and Lifestyle
      Study (a moderately sized network) and the Framingham Heart Study (FHS) (a large
      network).

PMID- 24729638
TI  - Modeling Menstrual Cycle Length and Variability at the Approach of Menopause
      Using Hierarchical Change Point Models.
AB  - As women approach menopause, the patterns of their menstrual cycle lengths
      change. To study these changes, we need to jointly model both the mean and
      variability of cycle length. Our proposed model incorporates separate mean and
      variance change points for each woman and a hierarchical model to link them
      together, along with regression components to include predictors of menopausal
      onset such as age at menarche and parity. Additional complexity arises from the
      fact that the calendar data have substantial missingness due to hormone use,
      surgery, and failure to report. We integrate multiple imputation and time-to
      event modeling in a Bayesian estimation framework to deal with different forms of
      the missingness. Posterior predictive model checks are applied to evaluate the
      model fit. Our method successfully models patterns of women's menstrual cycle
      trajectories throughout their late reproductive life and identifies change points
      for mean and variability of segment length, providing insight into the menopausal
      process. More generally, our model points the way toward increasing use of joint
      mean-variance models to predict health outcomes and better understand disease
      processes.

PMID- 24729639
TI  - A Bis(phosphine)-Modified Peptide Ligand for Stable and Luminescent Quantum Dots
      in Aqueous Media.
AB  - We describe a new class of ligands for semiconductor nanoparticles (quantum dots
      = QDs), which bind well and allow for their facile dissolution in aqueous
      solution. As a proof of principle, we have designed and synthesized a novel
      bis(phosphine)-modified peptide (BPMP) and shown that it has the ability to
      solubilize quantum dots in aqueous media. We further showed that the
      corresponding phosphine oxide derivatives of these new ligands are less good at
      solubilizing the quantum dots. These new bis(phosphine)-modified peptide ligands
      are easy to prepare and may well replace thiol-containing binding sequences in
      functionalized peptides for quantum dot coating, potentially resulting in quantum
      dots with higher quantum yields.

PMID- 24729640
TI  - Efficient Synthesis of the Cyclopentanone Fragrances (Z)-3-(2-oxopropyl)-2-(pent
      2-en-1-yl)cyclopentanone and Magnolione.
AB  - This paper describes the selective syntheses of two cis-isomer enriched
      cyclopentanone fragrances: (Z)-3-(2-oxopropyl)-2-(pent-2-en-1-yl)cyclopentanone
      (4 steps, 62% overall yield, 67% cis) and Magnolione(r) (5 steps, 60% overall
      yield, 55% cis). In addition, the asymmetric synthesis of (3aR,7aS)-5-methyl
      2,3,3a,4,7,7a-hexahydro-1H-inden-1-one as well as (3a'R,7a'S)-5'-methyl
      2',3',3a',4',7',7a'-hexahydrospiro[[1,3]dioxolane-2,1'-indene]) has been realized
      by an efficient kinetic resolution, which enables the selective synthesis of the
      2S,3R-isomer-enriched 3 and 4.

PMID- 24729642
TI  - SEPARATING THE EFFECTS OF ACOUSTIC AND PHONETIC FACTORS IN LINGUISTIC PROCESSING
      WITH IMPOVERISHED SIGNALS BY ADULTS AND CHILDREN.
AB  - Cochlear implants allow many individuals with profound hearing loss to understand
      spoken language, even though the impoverished signals provided by these devices
      poorly preserve acoustic attributes long believed to support recovery of phonetic
      structure. Consequently questions may be raised regarding whether traditional
      psycholinguistic theories rely too heavily on phonetic segments to explain
      linguistic processing while ignoring potential roles of other forms of acoustic
      structure. This study tested that possibility. Adults and children (8 years old)
      performed two tasks: one involving explicit segmentation, phonemic awareness, and
      one involving a linguistic task thought to operate more efficiently with well
      defined phonetic segments, short-term memory. Stimuli were unprocessed signals
      (UP), amplitude envelopes (AE) analogous to implant signals, and unprocessed
      signals in noise (NOI) which provided a degraded signal for comparison. Adults'
      results for short-term recall were similar for UP and NOI, but worse for AE
      stimuli. The phonemic awareness task revealed the opposite pattern across AE and
      NOI. Children's results for short-term recall showed similar decrements in
      performance for AE and NOI compared to UP, even though only NOI stimuli showed
      diminished results for segmentation. Conclusions were that perhaps traditional
      accounts are too focused on phonetic segments, something implant designers and
      clinicians need to consider.

PMID- 24729641
TI  - Examining the etiological associations among higher-order temperament dimensions.
AB  - A multivariate independent pathway model was used to examine the shared and
      unique genetic and environmental influences of Positive Affect (PA), Negative
      Affect (NA), and effortful control (EC) in a sample of 686 twin pairs (M age =
      10.07, SD = 1.74). There were common genetic influences and nonshared
      environmental influences shared across all three temperament dimensions and
      shared environmental influences in common to NA and EC. There were also
      significant independent genetic influences unique to PA and NA and significant
      independent shared environmental influences unique to PA. This study demonstrates
      that there are genetic and environmental influences that affect the covariance
      among temperament dimensions as well as unique genetic and environmental
      influences that influence the dimensions independently.

PMID- 24729644
TI  - Estimating False Discovery Proportion Under Arbitrary Covariance Dependence.
AB  - Multiple hypothesis testing is a fundamental problem in high dimensional
      inference, with wide applications in many scientific fields. In genome-wide
      association studies, tens of thousands of tests are performed simultaneously to
      find if any SNPs are associated with some traits and those tests are correlated.
      When test statistics are correlated, false discovery control becomes very
      challenging under arbitrary dependence. In the current paper, we propose a novel
      method based on principal factor approximation, which successfully subtracts the
      common dependence and weakens significantly the correlation structure, to deal
      with an arbitrary dependence structure. We derive an approximate expression for
      false discovery proportion (FDP) in large scale multiple testing when a common
      threshold is used and provide a consistent estimate of realized FDP. This result
      has important applications in controlling FDR and FDP. Our estimate of realized
      FDP compares favorably with Efron (2007)'s approach, as demonstrated in the
      simulated examples. Our approach is further illustrated by some real data
      applications. We also propose a dependence-adjusted procedure, which is more
      powerful than the fixed threshold procedure.

PMID- 24729643
TI  - Efficacy of Interpretation Bias Modification in Depressed Adolescents and Young
      Adults.
AB  - This study evaluated the efficacy of a four-session Cognitive Bias Modification
      Interpretation program for 45 depressed adolescents and young adults (14-21 years
      old; 12 males, 33 females; Beck Depressive Inventory, Second Edition >= 14)
      randomized to an active intervention condition (repeated exposure to positive
      outcomes of depression-relevant ambiguous scenarios; n=23) or a control condition
      (n=22). Both conditions experienced reductions on a Test of Interpretation Bias
      at post-treatment, with no significant between-group differences. When limited to
      those with negative bias at baseline, the intervention group showed greater
      improvement in interpretation bias at mid- and post-treatment. In addition, the
      intervention group overall had greater improvements in self-reported negative
      cognitions than the control group at post-intervention and two-week follow-up.
      However, there were no differences between groups in depression or anxiety
      symptom change. Potential factors contributing to mixed findings are discussed.

PMID- 24729645
TI  - Bayesian Models for Multiple Outcomes in Domains with Application to the
      Seychelles Child Development Study.
AB  - The Seychelles Child Development Study (SCDS) examines the effects of prenatal
      exposure to methylmercury on the functioning of the central nervous system. The
      SCDS data include 20 outcomes measured on 9-year old children that can be
      classified broadly in four outcome classes or "domains": cognition, memory,
      motor, and social behavior. Previous analyses and scientific theory suggest that
      these outcomes may belong to more than one of these domains, rather than only a
      single domain as is frequently assumed for modeling. We present a framework for
      examining the effects of exposure and other covariates when the outcomes may each
      belong to more than one domain and where we also want to learn about the
      assignment of outcomes to domains. Each domain is defined by a sentinel outcome
      which is preassigned to that domain only. All other outcomes can belong to
      multiple domains and are not preassigned. Our model allows exposure and covariate
      effects to differ across domains and across outcomes within domains, and includes
      random subject-specific effects which model correlations between outcomes within
      and across domains. We take a Bayesian MCMC approach. Results from the Seychelles
      study and from extensive simulations show that our model can effectively
      determine sparse domain assignment, and at the same time give increased power to
      detect overall, domain-specific and outcome-specific exposure and covariate
      effects relative to separate models for each endpoint. When fit to the Seychelles
      data, several outcomes were classified as partly belonging to domains other than
      their originally assigned domains. In retrospect, the new partial domain
      assignments are reasonable and, as we discuss, suggest important scientific
      insights about the nature of the outcomes. Checks of model misspecification were
      improved relative to a model that assumes each outcome is in a single domain.

PMID- 24729646
TI  - Modeling Bivariate Longitudinal Hormone Profiles by Hierarchical State Space
      Models.
AB  - The hypothalamic-pituitary-adrenal (HPA) axis is crucial in coping with stress
      and maintaining homeostasis. Hormones produced by the HPA axis exhibit both
      complex univariate longitudinal profiles and complex relationships among
      different hormones. Consequently, modeling these multivariate longitudinal
      hormone profiles is a challenging task. In this paper, we propose a bivariate
      hierarchical state space model, in which each hormone profile is modeled by a
      hierarchical state space model, with both population-average and subject-specific
      components. The bivariate model is constructed by concatenating the univariate
      models based on the hypothesized relationship. Because of the flexible framework
      of state space form, the resultant models not only can handle complex individual
      profiles, but also can incorporate complex relationships between two hormones,
      including both concurrent and feedback relationship. Estimation and inference are
      based on marginal likelihood and posterior means and variances. Computationally
      efficient Kalman filtering and smoothing algorithms are used for implementation.
      Application of the proposed method to a study of chronic fatigue syndrome and
      fibromyalgia reveals that the relationships between adrenocorticotropic hormone
      and cortisol in the patient group are weaker than in healthy controls.

PMID- 24729647
TI  - Auditory feedback control is involved at even sub-phonemic levels of speech
      production.

PMID- 24729648
TI  - Standing alone with prosodic help.
AB  - Two partially independent issues are addressed in two auditory rating studies:
      under what circumstances is a sub-string of a sentence identified as a stand
      alone sentence, and under what circumstances do globally ill-formed but 'locally
      coherent' analyses (Tabor, Galantucci, & Richardson., 2004) emerge? A new type of
      locally coherent structure is established in Experiment 1, where a that-less
      complement clause is at least temporarily analyzed as a stand-alone sentence when
      it corresponds to a prosodic phrase. In Experiment 2, reduced relative clause
      structures like those in Tabor et al. were investigated. As in Experiment 1, the
      root sentence (mis-)analyses emerged most frequently when the locally coherent
      clause corresponded to a prosodic phrase. However, a substantial number of
      locally coherent analyses emerged even without prosodic help, especially in
      examples with for-datives (which do not grammatically permit a reduced relative
      clause structure for some speakers). Overall, the results suggest that prosodic
      grouping of constituents encourages analysis of a sub-string as a root sentence,
      and raise the question of whether all local coherence structures involve analysis
      of an utterance-final sub-string as a root sentence.

PMID- 24729649
TI  - Incorporating Natural Helpers to Address Service Disparities for Young Children
      with Conduct Problems.
AB  - In response to the high levels of unmet need among historically underserved young
      children with conduct problems, this paper outlines some of the key issues
      involved in incorporating natural helpers into the delivery of parenting
      interventions for the treatment of conduct problems among historically
      underserved children. Strategies for the selection and training of natural
      helpers are discussed along with challenges that might be encountered in these
      processes. Directions for future research are also highlighted. With appropriate
      selection and training procedures in place, natural helpers may increase the
      accessibility of services for children and families and foster the reduction of
      service disparities.

PMID- 24729650
TI  - The Cost of Implementing New Strategies (COINS): A Method for Mapping
      Implementation Resources Using the Stages of Implementation Completion.
AB  - OBJECTIVE: Illustrate the value of a strategy used for measuring the costs and
      resources used in the implementation process over and above the costs of the
      intervention itself in the context of a two-arm randomized controlled trial.
      METHODS: Counties in California and Ohio (sites) were invited to implement
      Multidimensional Treatment Foster Care (MTFC), an alternative to congregate care
      for youth. Participating sites (n=53) were randomized to one of two
      implementation = sites share information and move through the implementation
      process as a cohort facilitated by an MTFC purveyor or (2) Individual
      Implementation (IND: "as usual") where sites work individually with the MTFC
      purveyor. The implementations were monitored using the Stages of Implementation
      Completion (SIC) measure of a number of observable activities, developed as part
      of the trial to segment the implementation process into 8 stages of
      implementation. Resource data gathered from the implementation purveyors and site
      participants were used to map costs onto each of the 8 stages to generate total
      cost measures stratified by type of resource and stage of implementation for each
      of the study arms. RESULTS: The SIC provided a feasible costing template to map
      costs onto observable activities and to enable the examination of important
      differences in implementation strategies for an evidence-based practice. The
      average total implementation cost prior to program start-up of CDT was $133,106;
      IND cost $118,699. While CDT cost more in a number of stages, it resulted in
      fewer county staff hours being used and shorter mean times to implementation than
      IND. In cases where rapidity of implementation of reducing staff time required
      for implementation is valued, then CDT would be the preferable implementation
      approach. CONCLUSIONS: The SIC is a useful tool for determining implementation
      resources needed for new evidence-based practice programs for youth and
      particularly for comparing different implementation strategies that might be
      tried in pilot programs.

PMID- 24729651
TI  - Recovery Migration to the City of New Orleans after Hurricane Katrina: A
      Migration Systems Approach.
AB  - Hurricane Katrina's effect on the population of the City of New Orleans provides
      a model of how severe weather events, which are likely to increase in frequency
      and strength as the climate warms, might affect other large coastal cities. Our
      research focuses on changes in the migration system - defined as the system of
      ties between Orleans Parish and all other U.S. counties - between the pre
      disaster (1999-2004) and recovery (2007-2009) periods. Using Internal Revenue
      Service county-to-county migration flow data, we find that in the recovery period
      Orleans Parish increased the number of migration ties with and received larger
      migration flows from nearby counties in the Gulf of Mexico coastal region,
      thereby spatially concentrating and intensifying the in-migration dimension of
      this predominantly urban system, while the out-migration dimension contracted and
      had smaller flows. We interpret these changes as the migration system relying on
      its strongest ties to nearby and less damaged counties to generate recovery in
      migration.

PMID- 24729652
TI  - Hyper-structure mining of frequent patterns in uncertain data streams.
AB  - Data uncertainty is inherent in many real-world applications such as sensor
      monitoring systems, location-based services, and medical diagnostic systems.
      Moreover, many real-world applications are now capable of producing continuous,
      unbounded data streams. During the recent years, new methods have been developed
      to find frequent patterns in uncertain databases; nevertheless, very limited work
      has been done in discovering frequent patterns in uncertain data streams. The
      current solutions for frequent pattern mining in uncertain streams take a FP-tree
      based approach; however, recent studies have shown that FP-tree-based algorithms
      do not perform well in the presence of data uncertainty. In this paper, we
      propose two hyper-structure-based false-positive-oriented algorithms to
      efficiently mine frequent itemsets from streams of uncertain data. The first
      algorithm, UHS-Stream, is designed to find all frequent itemsets up to the
      current moment. The second algorithm, TFUHS-Stream, is designed to find frequent
      itemsets in an uncertain data stream in a time-fading manner. Experimental
      results show that the proposed hyper-structure-based algorithms outperform the
      existing tree-based algorithms in terms of accuracy, runtime, and memory usage.

PMID- 24729653
TI  - Childless Elders in Assisted Living: Findings from the Maryland Assisted Living
      Study.
AB  - We compared data drawn from a random sample of 399 current assisted living (AL)
      residents and a subsample of 222 newly admitted residents for two groups:
      childless AL residents and AL residents with children. The percentage of
      childless AL residents (26%) in our study was slightly higher than US population
      estimates of childless persons age 65 and over (20%). In the overall sample, the
      two groups differed significantly by age, race and women's years of education.
      The childless group was slightly younger, had a higher percentage of African
      American residents, and had more years of education than the group with children.
      In the subsample, we looked at demographic, functional, financial and social
      characteristics and found that compared to residents with children, fewer
      childless residents had a dementia diagnosis, received visits from a relative
      while more paid less money per month for AL and reported having private
      insurance. As childlessness among older adults continues to increase, it will
      become increasingly important to understand how child status affects the need for
      and experience of long-term care.

PMID- 24729654
TI  - Improvement of thermal stability of polypropylene using DOPO-immobilized silica
      nanoparticles.
AB  - After the surface silylation with 3-methacryloxypropyltrimethoxysilane, silica
      nanoparticles were further modified by 9,10-dihydro-9-oxa-10-phosphaphenanthrene
      10-oxide (DOPO). The immobilization of DOPO on silica nanoparticles was confirmed
      by Fourier transform infrared spectroscopy, UV-visible spectroscopy, magic angle
      spinning nuclear magnetic resonance, and thermogravimetric analysis. By
      incorporating the DOPO-immobilized silica nanoparticles (5 wt%) into
      polypropylene matrix, the thermal oxidative stability exhibited an improvement of
      62  degrees C for the half weight loss temperature, while that was only 26 
      degrees C increment with incorporation of virgin silica nanoparticles (5 wt%).
      Apparent activation energies of the polymer nanocomposites were estimated via
      Flynn-Wall-Ozawa method. It was found that the incorporation of DOPO-immobilized
      silica nanoparticles improved activation energies of the degradation reaction.
      Based on the results, it was speculated that DOPO-immobilized silica
      nanoparticles could inhibit the degradation of polypropylene and catalyze the
      formation of carbonaceous char on the surface. Thus, thermal stability was
      significantly improved.

PMID- 24729655
TI  - Measuring Callous Unemotional Behaviors in Early Childhood: Factor Structure and
      the Prediction of Stable Aggression in Middle Childhood.
AB  - This study sought to replicate the results of our earlier study, which were
      published in this Journal (Willoughby et. al 2011), that used mother-reported
      items from the Achenbach System of Empirically Based Assessment to develop a
      screening measure of callous unemotional (CU) behaviors for use with preschool
      aged children. We further sought to extend those results by exploring the
      predictive validity of the CU measure with aggression trajectories in early-/mid
      childhood. The current study involved secondary data analysis of the NICHD Study
      of Early Childhood and Youth Development (NICHD-SECCYD) dataset. Factor analyses
      included N = 1176 children who participated in the age 3 year assessment of the
      NICHD-SECCYD. Predictive models included N = 1081 children for whom four of the
      six possible teacher ratings of aggressive behavior were available from annual
      assessments spanning 1st-6th grades. Consistent with prior work, a three-factor
      confirmatory factor model, which differentiated CU from oppositional defiant
      (ODD) and attention deficit/hyperactive-impulsive (ADHD) behaviors, provided the
      best fit to the data. Among children with disorganized attachment status, the
      combination of high levels of mother-rated ODD behaviors and CU behaviors, was
      predictive of stable elevated levels of teacher-rated aggression from 1st-6th
      grade (predicted probability = .38, compared with a base rate of .07). These
      results demonstrate that CU behaviors can be reliably measured by parent report
      in young children and are dissociable from more commonly assessed dimensions of
      disruptive behavior. Three-year-old children who exhibit elevated levels of ODD
      and CU behaviors, and who have disorganized attachments, are at increased risk
      for exhibiting elevated levels of aggression across middle childhood. Results are
      discussed from the perspective of early assessment and intervention.

PMID- 24729656
TI  - Branched Polyphosphazenes with Controlled Dimensions.
AB  - Using living cationic polymerization, a series of polyphosphazenes is prepared
      with precisely controlled molecular weights and narrow polydispersities. As well
      as varying chain length through the use of a living polymerization, amine-capped
      polyalkylene oxide (Jeffamine) side chains with varied lengths are grafted to the
      polymer backbone to give a series of polymers with varied dimensions. Dynamic
      light scattering and size exclusion chromatography are used to confirm the
      preparation of polymers with a variety of controlled dimensions and thus
      hydrodynamic volumes. Furthermore, it is demonstrated how the number of arms per
      repeat unit, and thus the density of branching, can also be further increased
      from two to four through using a one-pot thiolactone conversion of the
      Jeffamines, followed by thiol-yne addition to the polyphosphazene backbone. These
      densely branched, molecular brush-type polymers on a biodegradable
      polyphosphazene backbone all show excellent aqueous solubility and have potential
      in drug-delivery applications.

PMID- 24729657
TI  - Water-Soluble, Biocompatible Polyphosphazenes with Controllable and pH-Promoted
      Degradation Behavior.
AB  - The synthesis of a series of novel, water-soluble poly(organophosphazenes)
      prepared via living cationic polymerization is presented. The degradation
      profiles of the polyphosphazenes prepared are analyzed by GPC, 31P NMR
      spectroscopy, and UV-Vis spectroscopy in aqueous media and show tunable
      degradation rates ranging from days to months, adjusted by subtle changes to the
      chemical structure of the polyphosphazene. Furthermore, it is observed that these
      polymers demonstrate a pH-promoted hydrolytic degradation behavior, with a
      remarkably faster rate of degradation at lower pH values. These degradable, water
      soluble polymers with controlled molecular weights and structures could be of
      significant interest for use in aqueous biomedical applications, such as polymer
      therapeutics, in which biological clearance is a requirement and in this context
      cell viability tests are described which show the non-toxic nature of the
      polymers as well as their degradation intermediates and products.

PMID- 24729658
TI  - Mechanistic Imperatives for Deprotonation of Carbon Catalyzed by Triosephosphate
      Isomerase: Enzyme-Activation by Phosphite Dianion.
AB  - The mechanistic imperatives for catalysis of deprotonation of alpha-carbonyl
      carbon by triosephosphate isomerase (TIM) are discussed. There is a strong
      imperative to reduce the large thermodynamic barrier for deprotonation of carbon
      to form an enediolate reaction intermediate; and, a strong imperative for
      specificity in the expression of the intrinsic phosphodianion binding energy at
      the transition state for the enzyme-catalyzed reaction. Binding energies of 2 and
      6 kcal/mol, respectively, have been determined for formation of phosphite dianion
      complexes to TIM and to the transition state for TIM-catalyzed deprotonation of
      the truncated substrate glycolaldehyde [T. L. Amyes, J. P. Richard,
      Biochemistry2007, 46, 5841]. We propose that the phosphite dianion binding
      energy, which is specifically expressed at the transition state complex, is
      utilized to stabilize a rare catalytically active loop-closed form of TIM. The
      results of experiments to probe the role of the side chains of Ile172 and Leu232
      in activating the loop-closed form of TIM for catalysis of substrate
      deprotonation are discussed. Evidence is presented that the hydrophobic side
      chain of Ile172 assists in activating TIM for catalysis of substrate
      deprotonation through an enhancement of the basicity of the carboxylate side
      chain of Glu167. Our experiments link the two imperatives for TIM-catalyzed
      deprotonation of carbon by providing evidence that the phosphodianion binding
      energy is utilized to drive an enzyme conformational change, which results in a
      reduction in the thermodynamic barrier to deprotonation of the carbon acid
      substrate at TIM compared with the barrier for deprotonation in water. The
      effects of a P168A mutation on the kinetic parameters for the reactions of whole
      and truncated substrates are discussed.

PMID- 24729659
TI  - A MEMS-Based Approach to Single Nucleotide Polymorphism Genotyping.
AB  - Genotyping of single nucleotide polymorphisms (SNPs) allows diagnosis of human
      genetic disorders associated with single base mutations. Conventional SNP
      genotyping methods are capable of providing either accurate or high-throughput
      detection, but are still labor-, time-, and resource-intensive. Microfluidics has
      been applied to SNP detection to provide fast, low-cost, and automated
      alternatives, although these applications are still limited by either accuracy or
      throughput issues. To address this challenge, we present a MEMS-based SNP
      genotyping approach that uses solid-phase-based reactions in a single
      microchamber on a temperature control chip. Polymerase chain reaction (PCR),
      allele specific single base extension (SBE), and desalting on microbeads are
      performed in the microchamber, which is coupled with matrix-assisted laser
      desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) to analyze
      the SBE product. Experimental results from genotyping of the SNP on exon 1 of the
      HBB gene, which causes sickle cell anemia, demonstrate the potential of the
      device for rapid, accurate, multiplexed and high-throughput detection of SNPs.

PMID- 24729660
TI  - Nucleic Acid Isolation and Enrichment on a Microchip.
AB  - This paper presents a microchip that isolates and enriches target-binding single
      stranded DNA (ssDNA) from a randomized DNA mixture using a combination of solid
      phase extraction and electrophoresis. Strands of ssDNA in a randomized mixture
      are captured via specific binding onto target-functionalized microbeads in a
      microchamber. The strands are further separated from impurities and enriched on
      chip via electrophoresis. The microchip consists of two microchambers that are
      connected by a channel filled with agarose gel. In the isolation chamber, beads
      functionalized with human immunoglobulin E (IgE) are retained by a weir
      structure. An integrated heater elevates the temperature in the chamber to elute
      desired ssDNA from the beads, and electrophoretic transport of the DNA through
      the gel to the second chamber is accomplished by applying an electric potential
      difference between the two chambers. Experimental results show that ssDNA
      expressing binding affinity to IgE was captured and enriched from a sample of
      ssDNA with random sequences, demonstrating the potential of the microchip to
      enhance the sensitivity of ssDNA detection methods in dilute and complex
      biological samples.

PMID- 24729661
TI  - The effect of lysophosphatidic acid during in vitro maturation of bovine oocytes:
      embryonic development and mRNA abundances of genes involved in apoptosis and
      oocyte competence.
AB  - In the present study we examined whether LPA can be synthesized and act during in
      vitro maturation of bovine cumulus oocyte complexes (COCs). We found
      transcription of genes coding for enzymes of LPA synthesis pathway (ATX and PLA2)
      and of LPA receptors (LPAR 1-4) in bovine oocytes and cumulus cells, following in
      vitro maturation. COCs were matured in vitro in presence or absence of LPA (10(
      5) M) for 24 h. Supplementation of maturation medium with LPA increased mRNA
      abundance of FST and GDF9 in oocytes and decreased mRNA abundance of CTSs in
      cumulus cells. Additionally, oocytes stimulated with LPA had higher transcription
      levels of BCL2 and lower transcription levels of BAX resulting in the
      significantly lower BAX/BCL2 ratio. Blastocyst rates on day 7 were similar in the
      control and the LPA-stimulated COCs. Our study demonstrates for the first time
      that bovine COCs are a potential source and target of LPA action. We postulate
      that LPA exerts an autocrine and/or paracrine signaling, through several LPARs,
      between the oocyte and cumulus cells. LPA supplementation of maturation medium
      improves COC quality, and although this was not translated into an enhanced in
      vitro development until the blastocyst stage, improved oocyte competence may be
      relevant for subsequent in vivo survival.

PMID- 24729662
TI  - Early effects of a hypocaloric, Mediterranean diet on laboratory parameters in
      obese individuals.
AB  - Calorie restriction is a common strategy for weight loss in obese individuals.
      However, little is known about the impact of moderate hypocaloric diets on
      obesity-related laboratory parameters in a short-term period. Aim of this study
      was to evaluate the variation of laboratory biomarkers in obese individuals
      following a Mediterranean, hypocaloric (1400-1600 Kcal/die) diet. 23 obese,
      pharmacologically untreated patients were enrolled and subjected to the
      determination of anthropometric variables and blood collection at baseline, 1 and
      4 months after diet initiation. After 4 months of calorie restriction, we
      observed a significant decrease in body weight and BMI (both P < 0.0001), insulin
      (P = 0.037), HOMA-IR (P = 0.026), leptin (P = 0.008), and LDH (P = 0.023) and an
      increase in EGF (P = 0.013). All these parameters, except LDH, varied
      significantly already at 1 month after diet initiation. Also, lower levels of
      insulin (P = 0.025), leptin (P = 0.023), and EGF (P = 0.035) were associated with
      a greater (>5%) weight loss. Collectively, our data support a precocious
      improvement of insulin and leptin sensitivity after a modest calorie restriction
      and weight reduction. Moreover, EGF and LDH may represent novel markers of
      obesity, which deserve further investigations.

PMID- 24729663
TI  - Splenic stromal cells from aged mice produce higher levels of IL-6 compared to
      young mice.
AB  - Inflamm-aging indicates the chronic inflammatory state resulting from increased
      secretion of proinflammatory cytokines and mediators such as IL-6 in the elderly.
      Our principle objective was to identify cell types that were affected with aging
      concerning IL-6 secretion in the murine model. We compared IL-6 production in
      spleen cells from both young and aged mice and isolated several types of cells
      from spleen and investigated IL-6 mRNA expression and protein production. IL-6
      protein productions in cultured stromal cells from aged mice spleen were
      significantly high compared to young mice upon LPS stimulation. IL-6 mRNA
      expression level of freshly isolated stromal cells from aged mice was high
      compared to young mice. Furthermore, stromal cells of aged mice highly expressed
      IL-6 mRNA after LPS injection in vivo. These results suggest that stromal cells
      play a role in producing IL-6 in aged mice and imply that they contribute to the
      chronic inflammatory condition in the elderly. 

PMID- 24729664
TI  - Increased expression of chitinase 3-like 1 in aorta of patients with
      atherosclerosis and suppression of atherosclerosis in apolipoprotein E-knockout
      mice by chitinase 3-like 1 gene silencing.
AB  - INTRODUCTION: The purpose of this study was to investigate the changes of
      chitinase 3-like 1 (CHI3L1) in the aorta of patients with coronary
      atherosclerosis and to determine whether inhibition of CHI3L1 by lentivirus
      mediated RNA interference could stabilize atherosclerotic plaques in
      apolipoprotein E-knockout (ApoE(-/-)) mice. METHODS: We collected discarded
      aortic specimens from patients undergoing coronary artery bypass graft surgery
      and renal arterial tissues from kidney donors. A lentivirus carrying small
      interfering RNA targeting the expression of CHI3L1 was constructed. Fifty ApoE(-/
      ) mice were divided into control group and CHI3L1 gene silenced group. A
      constrictive collar was placed around carotid artery to induce plaques formation.
      Then lentivirus was transfected into carotid plaques. RESULTS: We found that
      CHI3L1 was overexpressed in aorta of patients with atherosclerosis and its
      expression was correlated with the atherosclerotic risk factors. After lentivirus
      transduction, mRNA and protein expression of CHI3L1 were attenuated in carotid
      plaques, leading to reduced plaque content of lipids and macrophages, and
      increased plaque content of collagen and smooth muscle cells. Moreover, CHI3L1
      gene silencing downregulated the expression of local proinflammatory mediators.
      CONCLUSIONS: CHI3L1 is overexpressed in aorta from patients with atherosclerosis
      and the lentivirus-mediated CHI3L1 gene silencing could represent a new strategy
      to inhibit plaques progression.

PMID- 24729665
TI  - Effect of microfibril twisting on theoretical powder diffraction patterns of
      cellulose Ibeta
AB  - Previous studies of calculated diffraction patterns for cellulose crystallites
      suggest that distortions that arise once models have been subjected to MD
      simulation are the result of both microfibril twisting and changes in unit cell
      dimensions induced by the empirical force field; to date, it has not been
      possible to separate the individual contributions of these effects. To provide a
      better understanding of how twisting manifests in diffraction data, the present
      study demonstrates a method for generating twisted and linear cellulose
      structures that can be compared without the bias of dimensional changes, allowing
      assessment of the impact of twisting alone. Analysis of unit cell dimensions,
      microfibril volume, hydrogen bond patterns, glycosidic torsion angles, and
      hydroxymethyl group orientations confirmed that the twisted and linear structures
      collected with this method were internally consistent, and theoretical powder
      diffraction patterns for the two were shown to be effectively indistinguishable.
      These results indicate that differences between calculated patterns for the
      crystal coordinates and twisted structures from MD simulation can result entirely
      from changes in unit cell dimensions, and not from microfibril twisting alone.
      Although powder diffraction patterns for models in the 81-chain size regime were
      shown to be unaffected by twisting, suggesting that a modest degree of twist is
      not inconsistent with experimental data, it may be that other diffraction
      techniques are capable of detecting this structural difference. Until such time
      as definitive experimental evidence comes to light, the results of this study
      suggest that both twisted and linear microfibrils may represent an appropriate
      model for cellulose Ibeta.

PMID- 24729666
TI  - Unpacking the Black Box of the CSRP Intervention: The Mediating Roles of Teacher
      child Relationship Quality and Self-regulation.
AB  - This study examines the theory of change of the Chicago School Readiness Project
      (CSRP), testing a sequence of theory-derived mediating mechanisms including the
      quality of teacher-child relationships and children's self-regulation. The CSRP
      is a multi-component teacher- and classroom-focused intervention, and its cluster
      randomized efficacy trial was conducted in 35 Head Start-funded classrooms. A
      series of increasingly complex and conservative structural equation models
      indicate that the CSRP carries its effects on children's academic and behavioral
      outcomes through changes in teacher-child relationship quality and children's
      self-regulation.

PMID- 24729667
TI  - Drug Use Trajectories After a Randomized Controlled Trial of MTFC: Associations
      with Partner Drug Use.
AB  - Trajectories of drug use were examined in a sample of women with prior juvenile
      justice system involvement. One hundred fifty-three young women who participated
      in a randomized controlled trial of Multidimensional Treatment Foster Care (MTFC)
      in adolescence were assessed on five occasions over a 24-month period in young
      adulthood (mean age = 22.29 years at T1). Participants assigned to the MTFC
      condition during adolescence reported greater decreases in drug use than girls
      assigned to the treatment as usual (TAU) condition. Partner drug use was
      significantly associated with women's concurrent drug use, although participants
      in the MTFC condition were more resilient to partner drug use than in the TAU
      condition. Implications for drug use prevention and intervention programs during
      adolescence are discussed.

PMID- 24729668
TI  - To Accept or Reject? The Impact of Adolescent Rejection Sensitivity on Early
      Adult Romantic Relationships.
AB  - Successfully navigating entry into romantic relationships is a key task in
      adolescence, which sensitivity to rejection can make difficult to accomplish.
      This study uses multi-informant data from a community sample of 180 adolescents
      assessed repeatedly from age 16 to 22. Individuals with elevated levels of
      rejection sensitivity at age 16 were less likely to have a romantic partner at
      age 22, reported more anxiety and avoidance when they did have relationships, and
      were observed to be more negative in their interactions with romantic partners.
      In addition, females whose rejection sensitivity increased during late
      adolescence were more likely to adopt a submissive pattern within adult romantic
      relationships, further suggesting a pattern in which rejection sensitivity
      forecasts difficulties.

PMID- 24729669
TI  - Spousal Bereavement Following Cancer Death.
AB  - Loss due to cancer could predispose surviving spouses or partners to a variety of
      negative outcomes. Although a terminal prognosis may provide opportunities to
      prepare for the loss, existing evidence is inconclusive as to whether death
      expectedness buffers potentially negative bereavement outcomes. Using data from
      the Living After Loss study, we examined longitudinally outcomes of bereaved
      individuals whose spouses/partners died from cancer (n = 112) versus other causes
      (n = 213) while accounting for death expectedness. While most of the cancer
      deaths were expected, more than half of the non-cancer deaths were not. The
      lowest levels of depression, grief, and loneliness over time were among those
      whose spouses/partners died expectedly from causes other than cancer. Cancer
      bereavement was as equally distressing as any unexpected death. Future efforts
      should focus on the mechanisms underlying these outcomes and develop effective
      and early interventions to those in greatest need.

PMID- 24729670
TI  - Smooth Scalar-on-Image Regression via Spatial Bayesian Variable Selection.
AB  - We develop scalar-on-image regression models when images are registered
      multidimensional manifolds. We propose a fast and scalable Bayes inferential
      procedure to estimate the image coefficient. The central idea is the combination
      of an Ising prior distribution, which controls a latent binary indicator map, and
      an intrinsic Gaussian Markov random field, which controls the smoothness of the
      nonzero coefficients. The model is fit using a single-site Gibbs sampler, which
      allows fitting within minutes for hundreds of subjects with predictor images
      containing thousands of locations. The code is simple and is provided in less
      than one page in the Appendix. We apply this method to a neuroimaging study where
      cognitive outcomes are regressed on measures of white matter microstructure at
      every voxel of the corpus callosum for hundreds of subjects.

PMID- 24729671
TI  - Functional Generalized Additive Models.
AB  - We introduce the functional generalized additive model (FGAM), a novel regression
      model for association studies between a scalar response and a functional
      predictor. We model the link-transformed mean response as the integral with
      respect to t of F{X(t), t} where F(.,.) is an unknown regression function and
      X(t) is a functional covariate. Rather than having an additive model in a finite
      number of principal components as in Muller and Yao (2008), our model
      incorporates the functional predictor directly and thus our model can be viewed
      as the natural functional extension of generalized additive models. We estimate
      F(.,.) using tensor-product B-splines with roughness penalties. A pointwise
      quantile transformation of the functional predictor is also considered to ensure
      each tensor-product B-spline has observed data on its support. The methods are
      evaluated using simulated data and their predictive performance is compared with
      other competing scalar-on-function regression alternatives. We illustrate the
      usefulness of our approach through an application to brain tractography, where
      X(t) is a signal from diffusion tensor imaging at position, t, along a tract in
      the brain. In one example, the response is disease-status (case or control) and
      in a second example, it is the score on a cognitive test. R code for performing
      the simulations and fitting the FGAM can be found in supplemental materials
      available online.

PMID- 24729672
TI  - Predischarge postpartum methicillin resistant Staphylococcus aureus infection and
      group B streptococcus carriage at the individual and hospital levels.
AB  - BACKGROUND: We sought to characterize the relationship between individual group B
      streptococcus (GBS) colonization and pre-discharge postpartum methicillin
      resistant Staphylococcus aureus (MRSA) infection in United States women
      delivering at term. We also sought to examine the association between hospital
      GBS colonization prevalence and MRSA infection. MATERIALS AND METHODS: Data was
      from the Nationwide Inpatient Sample, a representative sample of United States
      community hospitals. Hierarchical regression models were used to estimate odds
      ratios adjusted for patient age, race, expected payer, and prepregnancy diabetes
      and hospital teaching status, urbanicity, ownership, size, and geographic region.
      We used multiple imputation for missing covariate data. RESULTS: There were
      3,136,595 deliveries and 462 cases of MRSA infection included in this study. The
      odds ratio for individual GBS colonization was 1.2 (95% confidence interval: 0.9
      to 1.5). For a five-percent increase in the hospital prevalence of GBS
      colonization, the odds ratio was 0.9 (95% CI: 0.1 to 5.6). CONCLUSIONS: The odds
      ratio estimate for the association of hospital GBS prevalence with MRSA infection
      is too imprecise to make conclusions about its magnitude and direction. Barring
      major bias in our estimates, individual GBS carriage does not appear to be
      strongly associated with predischarge postpartum MRSA infection.

PMID- 24729673
TI  - The Role of Gastroesophageal Reflux and Microaspiration in Idiopathic Pulmonary
      Fibrosis.
AB  - There has been controversy regarding the relationship between gastroesophageal
      reflux, microaspiration, and idiopathic pulmonary fibrosis (IPF). In the last
      decade, there is increasing evidence supporting a relationship between
      gastroesophageal reflux, microaspiration, and IPF. Specifically, gastroesophageal
      reflux is common in IPF, is often asymptomatic in this population, and may impact
      disease progression and the natural history of IPF. More intriguing are the data
      suggesting that treatment of gastroesophageal reflux, either medical or surgical,
      may slow disease progression, as measured by change in forced vital capacity, and
      improve survival in IPF. Despite the growing evidence, there are still many gaps
      in our understanding of this relationship. Some of the major gaps include the
      discrepancy between the prevalence of gastroesophageal reflux in the general
      population compared to the prevalence of IPF, the unclear causative agent leading
      to injury, the lack of reliable methods to evaluate for gastroesophageal reflux
      and microaspiration, and the role of treatment. Further research, including a
      randomized controlled trial of anti-reflux therapy, needs to be done to clarify
      the relationship between gastroesophageal reflux, microaspiration, and IPF.

PMID- 24729674
TI  - Endoscopic papillary large balloon dilation reduces the need for mechanical
      lithotripsy in patients with large bile duct stones: a systematic review and meta
      analysis.
AB  - Background. Removal of large stones can be challenging and frequently requires
      the use of mechanical lithotripsy (ML). Endoscopic papillary large balloon
      dilation (EPLBD) following endoscopic sphincterotomy (ES) is a technique that
      appears to be safe and effective. However, data comparing ES + EPLBD with ES
      alone have not conclusively shown superiority of either technique. Objective. To
      assess comparative efficacies and rate of adverse events of these methods.
      Method. Studies were identified by searching nine medical databases for reports
      published between 1994 and 2013, using a reproducible search strategy. Only
      studies comparing ES and ES + EPLBD with regard to large bile duct stone
      extraction were included. Pooling was conducted by both fixed-effects and random
      effects models. Risk ratio (RR) estimates with 95% confidence interval (CI) were
      calculated. Results. Seven studies (involving 902 patients) met the inclusion
      criteria; 3 of 7 studies were prospective trials. Of the 902 patients, 463 were
      in the ES + EPLBD group, whereas 439 underwent ES alone. There were no
      differences noted between the groups with regard to overall stone clearance (98%
      versus 95%, RR   =   1.01 [0.97, 1.05]; P  = 0.60) and stone clearance at the 1st
      session (87% versus 79%, RR = 1.11 [0.98, 1.25]; P  = 0.11). ES + EPLBD was
      associated with a reduced need for ML compared to ES alone (15% versus 32%; RR  
      =   0.49 [0.32, 0.74]; P  =  0.0008) and was also associated with a reduction in
      the overall rate of adverse events (11% versus 18%; RR = 0.58 [0.41, 0.81]; P  =
      0.001). Conclusions. ES + EPLBD has similar efficacy to ES alone while
      significantly reducing the need for ML. Further, ES + EPLBD appears to be safe,
      with a lower rate of adverse events than traditional ES. ES + EPLBD should be
      considered as a first-line technique in the management of large bile duct stones.

PMID- 24729675
TI  - Determining the Number of Latent Classes in Single- and Multi-Phase Growth
      Mixture Models.
AB  - Stage-sequential (or multiphase) growth mixture models are useful for delineating
      potentially different growth processes across multiple phases over time and for
      determining whether latent subgroups exist within a population. These models are
      increasingly important as social behavioral scientists are interested in better
      understanding change processes across distinctively different phases, such as
      before and after an intervention. One of the less understood issues related to
      the use of growth mixture models is how to decide on the optimal number of latent
      classes. The performance of several traditionally used information criteria for
      determining the number of classes is examined through a Monte Carlo simulation
      study in single- and multi-phase growth mixture models. For thorough examination,
      the simulation was carried out in two perspectives: the models and the factors.
      The simulation in terms of the models was carried out to see the overall
      performance of the information criteria within and across the models, while the
      simulation in terms of the factors was carried out to see the effect of each
      simulation factor on the performance of the information criteria holding the
      other factors constant. The findings not only support that sample size adjusted
      BIC (ADBIC) would be a good choice under more realistic conditions, such as low
      class separation, smaller sample size, and/or missing data, but also increase
      understanding of the performance of information criteria in single- and multi
      phase growth mixture models.

PMID- 24729676
TI  - An albumin leader sequence coupled with a cleavage site modification enhances the
      yield of recombinant C-terminal Mullerian Inhibiting Substance.
AB  - Mullerian Inhibiting Substance (MIS) has been shown to inhibit ovarian cancer
      cells both in-vitro and in-vivo. Furthermore, recent evidence suggests that MIS
      may effectively target a putative ovarian cancer progenitor cell population
      enriched by a panel of CD44+, CD24+, Ep-CAM+, and E-cadherin-cell surface
      markers. In order to accommodate clinical testing of MIS in ovarian cancer
      patients, the production of recombinant human MIS must be optimized to increase
      yield and purity. Here we show that, compared to wild type, the substitution of
      the MIS leader sequence to that of human serum albumin, combined with a
      modification of the endogenous cleavage site from RAQR/S to a furin/kex2 RARR/S
      consensus site results in high expression, increased C-terminus cleavage and a
      reduction in unwanted cryptic internal cleavage products when produced in CHO
      cells. Purified MIS containing these alterations retains its capacity to induce
      regression of the Mullerian duct in fetal rat embryonic urogenital ridge assays.

PMID- 24729677
TI  - THERAPIST PERCEPTIONS OF INTIMATE PARTNER VIOLENCE: A REPLICATION OF HARWAY AND
      HANSEN2019;S STUDY AFTER MORE THAN A DECADE.
AB  - More than a decade ago, Hansen, Harway, and Cervantes (1991) and Harway and
      Hansen (1993) conducted a research study examining mental health providers'
      ability to accurately perceive violence within couples presenting for therapy and
      to intervene in a manner in which to reduce the risk of danger to couples. The
      results were alarming, with 40% of therapists sampled failing to perceive
      intimate partner violence (IPV) and virtually no therapists intervening to reduce
      the risk of lethality. Harway and colleagues questioned how well-trained and
      informed therapists were in assessing IPV. The present study replicates Harway
      and colleagues' study with the expectation that, over a decade later, therapists
      are better prepared to accurately identify IPV issues and intervene effectively
      to reduce the risk of lethality. Reproducing the two main procedures used in the
      original study, 111 psychologists, clinical social workers, and marriage and
      family therapists were asked to respond to a survey. Results show that therapists
      have indeed improved their ability to identify IPV issues. Twenty percent of
      therapists predicted an increase in conflict, compared to 4% in the original
      sample. However, almost no therapists accurately predicted lethality in either
      study. Implications concerning IPV training for therapists are discussed.

PMID- 24729678
TI  - Safety and effectiveness of a single-piece hydrophobic acrylic intraocular lens
      (enVista(r)) - results of a European and Asian-Pacific study.
AB  - PURPOSE: To evaluate the safety and effectiveness of a single-piece hydrophobic
      acrylic intraocular lens (IOL) (enVista(r) MX60; Bausch and Lomb Incorporated,
      Rochester, NY, USA) following implantation to correct aphakia subsequent to
      extracapsular cataract extraction in adults. SUBJECTS AND METHODS: This was an
      open-label, non-interventional, observational study conducted in 19 university
      and private-practice settings in Europe and the Asia-Pacific region to
      investigate clinical outcomes of the MX60 IOL in standard practice. Eligible
      subjects were at least 18 years of age and had undergone standard
      phacoemulsification and extracapsular cataract extraction with implantation of
      the MX60 IOL. The primary safety endpoint was the occurrence of adverse events,
      and the primary effectiveness endpoints included visual and refractive outcomes
      and stability, with data collected up to 2 years post-procedure. RESULTS: In this
      multicenter study, pooled data of 255 eyes were collected and analyzed. Excellent
      visual and refractive outcomes and stability were demonstrated. At postoperative
      visit 4 (61-180 days postoperative), 62.2% of subjects achieved a Snellen best
      corrected distance visual acuity (CDVA) of 20/20 (decimal 1.00), and 97.8% of
      subjects achieved a CDVA of 20/40 (decimal 0.50) or better. One eye (1.0%)
      underwent neodymium:yttrium aluminum garnet capsulotomy at 12 months post
      procedure. No glistenings of any grade were reported for any subject at any
      visit. Adverse events were infrequent and were consistent with incidences
      generally reported with cataract surgery. CONCLUSION: This study, which enrolled
      all comers, provided evidence of the excellent safety and effectiveness of the
      MX60 IOL in standard practice. Favorable clinical outcomes included outstanding
      visual and refractive outcomes and stability. No glistenings were reported at any
      postoperative visit.

PMID- 24729679
TI  - Subthreshold diode-laser micropulse photocoagulation as a primary and secondary
      line of treatment in management of diabetic macular edema.
AB  - BACKGROUND: The purpose of this study was to evaluate subthreshold diode-laser
      micropulse (SDM) photocoagulation as a primary and secondary line of treatment
      for clinically significant diabetic macular edema (CSDME). METHODS: In this
      prospective nonrandomized case series, 220 cases of nonischemic CSDME were
      managed primarily and secondarily by SDM photocoagulation on a 15% duty cycle
      with a mean power of 828 mW and a spot size of 75-125 MUm. SDM treatment was
      repeated at 3-4-month intervals if residual leakage was observed. Additional
      intravitreal pharmacologic therapy was used according to the response. Follow-up
      varied from 12 to 19 (mean 14+/-2.8) months. Novel software designed by the
      authors was used to record the subvisible threshold laser applications and their
      parameters on the fundus image of the eye. Evaluation of the results of treatment
      was done using fluorescein angiography and optical coherence tomography (OCT).
      Primary outcome measures included changes in visual acuity and foveal thickness
      at OCT. Secondary outcome measures included visual loss of one or more Snellen
      lines and laser scars detectable on fundus biomicroscopy or fluorescein
      angiography. RESULTS: In the primary treatment group, there was significant
      improvement or stabilization of visual acuity after the first 3-4 months, which
      was stable thereafter. Visual acuity was stable in the secondary treatment group.
      A corresponding reduction of macular thickness on OCT was noted during the follow
      up period in both groups. Additional therapy included repeat SDM
      photocoagulation, intravitreal injection of triamcinolone, and pars plana
      vitrectomy. Laser marks seen as changes in retinal pigment epithelium on fundus
      biomicroscopy and fluorescein angiography were noted in 3.3% and 5.7% of cases.
      Our novel software could accurately record the location of all SDM-invisible
      applications. CONCLUSION: Micropulse laser is an effective minimal intensity
      therapy that offers the clear advantage of minimizing or avoiding laser-induced
      visible retinal burn/scarring while reducing the foveal thickness in the
      management of selected cases of CSDME. Future prospective studies should include
      the use of SDM photocoagulation as a combined minimally invasive therapy to
      consolidate the prompt but temporary effects of anti-vascular endothelial growth
      factor or anti-inflammatory agents. Virtual localization of SDM-invisible
      applications using our proprietary software could be used to guide further
      retreatments.

PMID- 24729680
TI  - High-cylinder toric intraocular lens implantation versus combined surgery of low
      cylinder intraocular lens implantation and limbal relaxing incision for high
      astigmatism eyes.
AB  - Clinical outcomes were compared between high-cylinder toric intraocular lens
      (IOL) implantation and the combined surgery of low-cylinder toric IOL
      implantation and limbal relaxing incision (LRI) for correcting preexisting high
      amplitude corneal astigmatism. Fifty-seven eyes with preexisting corneal
      astigmatism of 2.5 diopter (D) or greater were divided into the following two
      groups: (1) eyes that underwent Alcon AcrySof(r) IQ Toric T6, T7, T8, or T9 IOL
      implantation (toric group); and (2) eyes that underwent the combined surgery of
      AcrySof(r) IQ Toric T5 IOL implantation and LRI (LRI group). Uncorrected visual
      acuity (UCVA), best-corrected visual acuity (BCVA), manifest, refractive and
      corneal cylinder (MC, RC, CC), were compared postoperatively. Corneal and ocular
      higher-order aberrations (HOA) were also compared. At 1 day postoperative, UCVA
      was significantly better and MC and RC were significantly less in the toric
      group, however, at 1 and 6 months postoperative, there was no significant
      difference in those parameters. Postoperative corneal and ocular HOA were
      significantly greater in the LRI Group. For correcting astigmatism in eyes with a
      high amount of preexisting astigmatism, high-cylinder toric IOL implantation
      achieves better clinical outcomes, especially in the early postoperative period,
      than the combined procedure of moderate-cylinder toric IOL implantation and LRI. 

PMID- 24729681
TI  - Virtual reality simulator for vitreoretinal surgery using integrated OCT data.
AB  - Operative practice using surgical simulators has become a part of training in
      many surgical specialties, including ophthalmology. We introduce a virtual
      reality retina surgery simulator capable of integrating optical coherence
      tomography (OCT) scans from real patients for practicing vitreoretinal surgery
      using different pathologic scenarios. 

PMID- 24729682
TI  - Characteristics of intraretinal deposits in acute central serous
      chorioretinopathy.
AB  - PURPOSE: To describe the temporal and spatial characteristics of intraretinal
      deposits in patients with acute central serous chorioretinopathy (CSC) using
      spectral domain optical coherence tomography (OCT). MATERIALS AND METHODS: We
      retrospectively reviewed the medical records of all patients that presented with
      acute CSC to Weill Cornell Medical College from January 2012 to May 2013. Acute
      CSC was defined as a diagnosis of CSC within 4 months of the onset of symptoms.
      Only one eye per patient was included in the study. Each patient was imaged with
      spectral domain OCT at the initial office visit. The decision to reimage these
      patients was made by the treating physician. RESULTS: A total of 25 patients (25
      eyes; 17 men and eight nonpregnant women) were included in this review. Seven of
      25 patients (28%) demonstrated intraretinal deposits within the outer plexiform
      layer during the initial OCT, with deposits appearing as early as the same day as
      the onset of symptoms. A total of 25 of 25 patients (100%) demonstrated
      intraretinal deposits in the outer nuclear layer upon initial (76%) or follow-up
      OCT, as early as 2 days after the onset of symptoms. A total of 24 of 25 patients
      (96%) demonstrated deposits in the external limiting membrane upon a follow-up
      OCT, as early as 7 days from symptoms appearing. A total of 24 of 25 patients
      (96%) developed intraretinal deposits in the inner segment/outer segment layer
      upon follow-up OCT, appearing as early as 14 days after symptom onset. At the
      time of resolution of subretinal fluid, 20 of 25 patients (80%) demonstrated
      intraretinal deposits. CONCLUSION: Intraretinal deposits are present in the outer
      retinal layers in patients with acute CSC, with the deposits appearing
      progressively deeper within the retina as the condition evolves. Upon resolution
      of subretinal fluid, the deposits slowly resolve.

PMID- 24729683
TI  - Two cases of malignant glaucoma unresolved by pars plana vitrectomy.
AB  - Malignant glaucoma, which is characterized by a shallow or flat anterior chamber
      with high intraocular pressure, can usually be resolved by pars plana vitrectomy
      with anterior hyaloidectomy. We describe two cases in which malignant glaucoma
      was refractory to conventional treatment and complete vitrectomy. Case one an 88
      year-old woman with pseudoexfoliation glaucoma underwent trabeculotomy and
      subsequently developed malignant glaucoma. Four months after transient recovery
      by pars plana vitrectomy, the malignant glaucoma recurred. She underwent
      peripheral iridectomy and local zonulectomy with successful control of her
      intraocular pressure. In case two, an 85-year-old man had a history of
      pseudoexfoliation glaucoma. Seven months after phacoemulsification and
      intraocular lens implantation, he developed malignant glaucoma that was
      refractory to pars plana vitrectomy. He underwent peripheral iridectomy,
      goniosynechialysis and trabectome surgery resulting in the successful control of
      his intraocular pressure. In rare cases of malignant glaucoma refractive to
      vitrectomy, peripheral iridectomy with or without local zonulectomy is a
      reasonable and minimally invasive surgical procedure. 

PMID- 24729684
TI  - Terson syndrome and leukemia: a case report.
AB  - BACKGROUND: Terson syndrome is defined as intraocular hemorrhage associated with
      intracranial bleeding. This syndrome can occur in the event of intracranial
      hemorrhage or elevated intracranial pressure. To our knowledge, it has never been
      associated with chronic myeloid leukemia. A 45-year-old woman suffering from
      chronic myeloid leukemia was referred to our clinic with Terson syndrome after
      intracranial bleeding. We followed this patient for a year, performing visual
      acuity assessment, fundus examination, color retinography, and A-scan and B-scan
      ultrasonography. At presentation, her best-corrected visual acuity on the right
      was 20/63 and on the left was 20/320. In the right eye, retinoscopy showed
      blurring of the optic margins surrounded by retinal and preretinal hemorrhages,
      preretinal fibrosis of the optic disc along the vascular arcades, and
      perivascular retinal infiltrates. In the left eye, the optic disc was surrounded
      by retinal and preretinal hemorrhages, and massive fibrosis with hard exudates
      and severe preretinal hemorrhage were observed at the posterior pole. Roth spots
      and many circular hemorrhages were noted at the periphery of the retina. A-scan
      and B-scan ultrasonography did not show intraocular leukemic infiltration. The
      clinical picture remained stable over the following 12 months. In this patient,
      we observed the ophthalmoscopic features of chronic myeloid leukemia, but also
      coexistence of features typical of Terson syndrome. To our knowledge, no similar
      cases have been reported previously.

PMID- 24729686
TI  - Fc-fusion technology and recombinant FVIII and FIX in the management of the
      hemophilias.
AB  - Prophylaxis with regular infusions of factor VIII (FVIII)- or factor IX (FIX)-
      containing products is the mainstay of modern hemophilia care. However, this
      therapeutic regimen is inconvenient, requiring repeated intravenous injections
      from childhood. Approaches meant to prolong the half-life of FVIII and FIX in
      plasma have been developed in order to improve the feasibility and acceptability
      of replacement therapy, extending protection from bleeding, reducing infusion
      frequency and hence the need for venous access devices in young children. Several
      strategies have been implemented to enhance the pharmacokinetics of clotting
      factors, including conjugation with polyethylene glycol and the production by
      genetic engineering of fusion proteins containing the coagulation factors linked
      to a long-lived plasma protein such as albumin or the Fc fragment of
      immunoglobulin (Ig)G. The latter technology is one of the most promising, since
      the prolongation of FVIII and FIX half-life is obtained by exploiting the
      physiological binding of the Fc domain to the neonatal Fc receptor. Fc fusion
      monomers have been obtained with both recombinant FVIII (rFVIIIFc) and FIX
      (rFIXFc), and data from preclinical and clinical studies showed improved
      pharmacokinetics for both factors, which are produced in human embryonic kidney
      (HEK) 293 cells, thus ensuring full human post-translational modifications. In
      Phase I/IIa studies, rFVIIIFc and rFIXFc showed 1.5-1.7 fold and 3.0-4.0 fold
      longer elimination half-life, respectively. Similar data have been obtained in
      the Phase III clinical studies with rFVIIIFc and rFIX-Fc published recently. Both
      drugs were satisfactorily safe, particularly with respect to immunogenicity, and
      no serious adverse event was observed.

PMID- 24729685
TI  - Tocilizumab in the treatment of rheumatoid arthritis and beyond.
AB  - Rheumatoid arthritis (RA) is a systemic inflammatory disease characterized by
      joint pain, swelling, stiffness, and progressive destruction of the small joints
      of the hands and feet. Treatment of RA has improved over the past decade. With
      multiple cytokines well-known now to play a role in the pathogenesis of RA,
      including tumor necrosis factor alpha, interleukin (IL)-1beta, and IL-6, many
      targeted biological treatments against these cytokines have emerged, changing the
      treatment of this disease. Tocilizumab (TCZ) is a recombinant humanized
      monoclonal antibody against the IL-6 receptor and has been approved in many
      countries, including the United States, for the treatment of moderate to severe
      RA in patients who have not adequately responded to one or more disease-modifying
      antirheumatic drugs (DMARDs) or cannot tolerate other approved drug classes for
      RA. The aim of this review is to discuss the role of IL-6 in RA, and to provide
      an overview of the mode of action, pharmacokinetics, and safety of TCZ.
      Furthermore, efficacy studies of TCZ as both monotherapy and combination therapy
      will be evaluated. There have been several important clinical trials evaluating
      the efficacy and safety of TCZ in RA patients; this review summarizes this data
      from 14 key trials with emphasis on Phase III trials. Review of these trials
      provides strong evidence that its use, both as monotherapy and in combination
      with methotrexate or other DMARDs, is an effective treatment in reducing the
      signs and symptoms of RA. TCZ showed tolerable safety but care is required for
      its use since there are some important safety concerns including elevated liver
      enzymes, elevated low-density lipoprotein, infections, and gastrointestinal
      perforations. Additionally, given the efficacy of TCZ in the treatment of RA,
      this review discusses how TCZ may be beneficial in the treatment of other
      autoimmune diseases, spinal disease, cardiovascular disease, organ
      transplantation, and malignancies where elevated levels of IL-6 may play a role
      in the pathogenesis of these diseases.

PMID- 24729687
TI  - Budget impact of switching from an immediate-release to a prolonged-release
      formulation of tacrolimus in renal transplant recipients in the UK based on
      differences in adherence.
AB  - BACKGROUND AND AIMS: Advagraf is a once-daily prolonged-release formulation of
      tacrolimus with proven noninferiority to Prograf, a twice-daily immediate-release
      formulation of tacroli-mus, in biopsy-proven acute rejection, graft survival and
      patient survival in renal transplant recipients. Advagraf is associated with
      improved adherence compared with Prograf, which may ultimately improve long-term
      outcomes. The present study assessed the budget impact of switching patients from
      Prograf to Advagraf in the UK. MATERIALS AND METHODS: A budget-impact model was
      constructed based on published data on acute rejection, graft failure, and
      mortality in the UK setting. Patients were assumed to convert from Prograf to
      Advagraf on a 1:1 milligram:milligram basis. In a study comparing the adherence
      rates between once-daily versus twice-daily formulations of tacrolimus, the
      proportion of patients taking the prescribed number of daily doses was 88.2% in
      Advagraf patients and 78.8% in Prograf patients. The model applied a relative
      risk of graft failure of 3.47 to nonadherent patients based on data from a 2004
      meta-analysis (based on graft-failure rates of 1.3%-40.0% in adherent patients,
      compared with 6.1%-100% in nonadherent patients). Cost data were taken from the
      March 2013 British National Formulary and 2012-2013 National Health Service
      tariff information. The analysis was performed over a 5-year time horizon and
      future costs were not discounted, in line with International Society for
      Pharmacoeconomics and Outcomes Research guidelines. RESULTS: Over a 5-year time
      horizon, the mean cost per patient (including tacrolimus, concomitant
      immunosuppressive medications, dialysis after graft failure, and treatment for
      acute rejection) was L29,328 (standard deviation [SD] L2,844) for Advagraf versus
      L33,061 (SD L3,178) for Prograf. The total cost saving of L3,733 (SD L530) was
      driven primarily by reduced dialysis costs arising from the lower incidence of
      graft failure (21.6% with Prograf versus 18.3% with Advagraf) in the larger
      proportion of adherent patients in the Advagraf arm. In a hypothetical transplant
      centre of 100 kidney-transplant recipients, this would result in cost savings
      approaching L375,000 over 5 years. CONCLUSION: Conversion of renal transplant
      recipients from Prograf to Advagraf was associated with lower pharmacy and
      dialysis costs, with the reduction in dialysis costs being driven by improved
      adherence to Advagraf regimen and the consequent improvement in graft survival.

PMID- 24729689
TI  - Treatment selection and experience in multiple sclerosis: survey of neurologists.
AB  - BACKGROUND: Multiple sclerosis (MS) is a complex disease with many therapeutic
      options. Little is known about how neurologists select particular disease
      modifying therapies (DMTs) for their patients. OBJECTIVE: To understand how
      neurologists make decisions regarding the prescription of DMTs for patients with
      MS, and to explore neurologists' experiences with individual DMTs. METHODS: From
      December 2012 to January 2013, members of a nationwide physician market research
      panel were sent an online study invitation with a link to a survey website.
      Eligible neurologists were included if they currently practice medicine in the
      United States, and if they treat >=20 patients with MS. RESULTS: A total of 102
      neurologists (n=63 general neurologists; n=39 MS specialists; 81.4% male)
      completed the survey. The mean (standard deviation) number of years in practice
      since completing medical training was 16.4 (8.6) years. Overall, the most
      commonly prescribed DMTs were subcutaneous interferon (IFN) beta-1a and
      glatiramer acetate; approximately 5.5% of patients were untreated. The most
      important attributes of DMT medication selection were (in order of importance)
      efficacy, safety, tolerability, patient preference, and convenience. The DMT with
      the highest neurologist-reported percentage of patients who were "Very/Extremely
      Satisfied" with their therapy was fingolimod (31.0%), followed by glatiramer
      acetate (13.9%; P=0.017). Compared with fingolimod (94.0%), significantly fewer
      (P<0.05) neurologists reported that "All/Most" of their patients were adherent to
      treatment with glatiramer acetate (78.0%), subcutaneous IFN beta-1a (84.0%), and
      IFN beta-1b (75.0%); no significant differences were observed with intramuscular
      IFN beta-1a (92.9%; P=0.75). Patients' calls to neurologists' offices were most
      commonly related to side effects for all self-injectable DMTs, whereas calls
      about fingolimod primarily involved insurance coverage issues. CONCLUSION: Our
      survey results showed that very few patients with MS did not received any DMT.
      Among the DMTs available at the time of the survey, neurologists reported that
      patients were most satisfied with, and adherent to, fingolimod, but these
      patients also faced more problems with insurance coverage when compared with
      those taking self-injectable DMTs.

PMID- 24729688
TI  - Alcohol use, antiretroviral therapy adherence, and preferences regarding an
      alcohol-focused adherence intervention in patients with human immunodeficiency
      virus.
AB  - BACKGROUND: The primary objectives of this study were to determine the
      association between alcohol and antiretroviral therapy (ART) adherence and the
      perceived appropriateness and acceptability of elements of an adherence
      counseling program with a focus on alcohol-related ART nonadherence among a
      sample of ART recipients in human immunodeficiency virus (HIV) clinics in
      Tshwane, South Africa. METHODS: We conducted a cross-sectional study with
      purposive sampling. The sample comprised 304 male and female ART recipients at
      two President's Emergency Plan For AIDS Relief-supported HIV clinics. Using an
      interview schedule, we assessed patients' alcohol use (Alcohol Use Disorders
      Identification Test), other drug use, level of adherence to ART, and reasons for
      missing ART doses (AIDS Clinical Trials Group adherence instrument).
      Additionally, patients' views were solicited on: the likely effectiveness of
      potential facilitators; the preferred quantity, duration, format, and setting of
      the sessions; the usefulness of having family members/friends attend sessions
      along with the patient; and potential skill sets to be imparted. RESULTS: About
      half of the male drinkers' and three quarters of the female drinkers' Alcohol Use
      Disorders Identification Test scores were suggestive of hazardous or harmful
      drinking. Average self-reported ART adherence was 89.7%. There was a significant
      association between level of alcohol use and degree of ART adherence. Overall,
      participants perceived two clinic-based sessions, each of one hour's duration, in
      a group format, and facilitated by a peer or adherence counselor, as most
      appropriate and acceptable. Participants also had a favorable attitude towards
      family and friends accompanying them to the sessions. They also favored an
      alcohol-focused adherence counseling program that employs motivational
      interviewing and cognitive behavioral therapy-type approaches. CONCLUSION: The
      association between alcohol use and ART nonadherence points to a need for alcohol
      focused ART adherence interventions. Patients' perceptions suggest their
      amenability to clinic-based brief motivational interviewing and cognitive
      behavioral therapy-type adherence interventions delivered by lay persons in group
      settings. Further research should investigate how best to implement such
      interventions in the existing health system.

PMID- 24729690
TI  - Shared decision-making: the perspectives of young adults with type 1 diabetes
      mellitus.
AB  - BACKGROUND: Shared decision-making (SDM) is at the core of patient-centered care.
      We examined whether young adults with type 1 diabetes perceived the clinician
      groups they consulted as practicing SDM. METHODS: In a web-based survey, 150
      Australians aged 18-35 years and with type 1 diabetes rated seven aspects of SDM
      in their interactions with endocrinologists, diabetes educators, dieticians, and
      general practitioners. Additionally, 33 participants in seven focus groups
      discussed these aspects of SDM. RESULTS: Of the 150 respondents, 90% consulted
      endocrinologists, 60% diabetes educators, 33% dieticians, and 37% general
      practitioners. The majority of participants rated all professions as oriented
      toward all aspects of SDM, but there were professional differences. These ranged
      from 94.4% to 82.2% for "My clinician enquires about how I manage my diabetes";
      93.4% to 82.2% for "My clinician listens to my opinion about my diabetes
      management"; 89.9% to 74.1% for "My clinician is supportive of my diabetes
      management"; 93.2% to 66.1% for "My clinician suggests ways in which I can
      improve my self-management"; 96.6% to 85.7% for "The advice of my clinician can
      be understood"; 98.9% to 82.2% for "The advice of my clinician can be trusted";
      and 86.5% to 67.9% for "The advice of my clinician is consistent with other
      members of the diabetes team". Diabetes educators received the highest ratings on
      all aspects of SDM. The mean weighted average of agreement to SDM for all
      consultations was 84.3%. Focus group participants reported actively seeking
      clinicians who practiced SDM. A lack of SDM was frequently cited as a reason for
      discontinuing consultation. The dominant three themes in focus group discussions
      were whether clinicians acknowledged patients' expertise, encouraged patients'
      autonomy, and provided advice that patients could utilize to improve self
      management. CONCLUSION: The majority of clinicians engaged in SDM. Young adults
      with type 1 diabetes prefer such clinicians. They may fail to take up recommended
      health services when clinicians do not practice this component of patient
      centered care. Such findings have implications for patient safety, improved
      health outcomes, and enhanced health service delivery.

PMID- 24729691
TI  - Impact of patient satisfaction ratings on physicians and clinical care.
AB  - BACKGROUND: Although patient satisfaction ratings often drive positive changes,
      they may have unintended consequences. OBJECTIVE: The study reported here aimed
      to evaluate the clinician-perceived effects of patient satisfaction ratings on
      job satisfaction and clinical care. METHODS: A 26-item survey, developed by a
      state medical society in 2012 to assess the effects of patient satisfaction
      surveys, was administered online to physician members of a state-level medical
      society. Respondents remained anonymous. RESULTS: One hundred fifty five
      physicians provided responses (3.9% of the estimated 4,000 physician members of
      the state-level medical society, or approximately 16% of the state's emergency
      department [ED] physicians). The respondents were predominantly male (85%) and
      practicing in solo or private practice (45%), hospital (43%), or academia (15%).
      The majority were ED (57%), followed by primary care (16%) physicians. Fifty-nine
      percent reported that their compensation was linked to patient satisfaction
      ratings. Seventy-eight percent reported that patient satisfaction surveys
      moderately or severely affected their job satisfaction; 28% had considered
      quitting their job or leaving the medical profession. Twenty percent reported
      their employment being threatened because of patient satisfaction data. Almost
      half believed that pressure to obtain better scores promoted inappropriate care,
      including unnecessary antibiotic and opioid prescriptions, tests, procedures, and
      hospital admissions. Among 52 qualitative responses, only three were positive.
      CONCLUSION: These pilot-level data suggest that patient satisfaction survey
      utilization may promote, under certain circumstances, job dissatisfaction,
      attrition, and inappropriate clinical care among some physicians. This is
      concerning, especially in the context of the progressive incorporation of patient
      satisfaction ratings as a quality-of-care metric, and highlights the need for a
      rigorous evaluation of the optimal methods for survey implementation and
      utilization.

PMID- 24729692
TI  - Management of osteoporosis with calcitriol in elderly Chinese patients: a
      systematic review.
AB  - Osteoporosis, a skeletal disorder characterized by a reduction in bone strength,
      is becoming a major public health problem in the People's Republic of China, with
      a rapid increase observed among the population. Chinese guidelines particularly
      recommend use of active vitamin D in managing osteoporosis. 1,25-(OH)2D3
      (calcitriol) is an active vitamin D metabolite. It plays a role in many
      biological processes, especially in bone metabolism and muscle function, and is
      mediated by vitamin D receptors. Osteoporosis in elderly men and women is
      characterized by uncoupled bone remodeling, which is induced by sex hormone
      deficiencies, somatopause, vitamin D deficiency, reduced synthesis of D hormone,
      and lack of receptors or receptor affinity for D hormone in target organs.
      Reviewed here are six randomized controlled trials on calcitriol monotherapy and
      five on calcitriol therapy combined with other antiosteoporotic agents. Evidence
      from these trials shows that calcitriol monotherapy can improve bone mineral
      density in elderly osteoporotic Chinese patients but may be insufficient for long
      term treatment. Calcitriol can also decrease bone turnover markers and bring
      about significant improvements in muscle strength. Further, calcitriol in
      combination with other therapeutic bone agents was shown to be well tolerated and
      capable of additional bone-preserving effects compared with use of calcitriol
      alone in areas including bone mineral density, bone turnover markers, bone pain
      improvement, and fracture incidence. Hypercalcemia and hypercalciuria, the most
      common side effects of calcitriol therapy, were not documented in the trials
      reviewed, and might have been the result of the low dosages used. One study
      showed that treatment with calcitriol can improve quality of life in patients
      with osteoporosis, although not to the same extent as bisphosphonates. 

PMID- 24729693
TI  - The clinical usefulness of central hemodynamics to evaluate diastolic dysfunction
      in subjects without hypertension.
AB  - OBJECTIVE: Diastolic dysfunction is associated with increased arterial stiffness
      in patients with hypertension. However, the role of arterial stiffness in
      diastolic dysfunction in subjects without hypertension has not been fully
      established. MATERIALS AND METHODS: A total of 287 subjects (male:female ratio
      121:166, mean age 53.0+/-14.4 years) without hypertension or any heart disease
      who simultaneously received transthoracic echocardiography and noninvasively
      semiautomated radial artery applanation tonometry (with an Omron HEM-9000AI) in
      the Department of Internal Medicine, St Vincent's Hospital, from July 2011 to
      September 2012, were enrolled in this study. RESULTS: A total of 147 subjects
      (male:female ratio 59:88, mean age 61.7+/-9.9 years), representing 51.2% of the
      287 subjects, had diastolic dysfunction (defined as abnormal relaxation pattern
      of mitral inflow). There were significant differences in systolic blood pressure
      (BP), pulse pressure, late systolic peak pressure (SBP2), and radial augmentation
      index (RaAIx) between normal diastolic function and diastolic dysfunction.
      DeltaBP was defined as systolic BP minus SBP2, because of the difference in
      systolic BP between the two groups. DeltaBP (odds ratio [OR] 1.059, 95%
      confidence interval [CI] 1.005-1.115; P=0.032) and RaAIx (odds ratio 1.027, 95%
      CI 1.009-1.044, P=0.003) were associated with diastolic dysfunction. A receiver
      operating-characteristic curve showed that DeltaBP (area under the curve 0.875,
      95% CI 0.832-0.911) and RaAIx (area under the curve 0.878, 95% CI 0.835-0.914)
      were associated with diastolic dysfunction. CONCLUSION: We found that DeltaBP and
      increased RaAIx were associated with diastolic dysfunction in subjects without
      hypertension after adjustment for age and sex. Therefore, it is suggested that
      noninvasive estimation of central BP may be useful to reflect diastolic
      dysfunction in subjects with normal peripheral BP.

PMID- 24729695
TI  - Progressive dysphagia and neck pain due to diffuse idiopathic skeletal
      hyperostosis of the cervical spine: a case report and literature review.
AB  - Diffuse idiopathic skeletal hyperostosis (DISH) is considered an underdiagnosed
      and mostly asymptomatic nonprimary osteoarthritis. The etiology of DISH remains
      unknown and the validated diagnostic criteria are absent. This condition is still
      recognized radiologically only. Rarely, large projecting anterior osteophytes
      result in esophageal impingement and distortion leading to dysphagia. We report
      the case of progressive dysphagia and neck pain due to DISH of the cervical spine
      in a 70-year-old man, which was surgically removed with excellent postoperative
      results and complete resolution of symptoms. Imaging studies, surgical findings,
      and histopathological examinations were used to support the diagnosis. The
      patient was successfully treated with total excision of the anterior osteophytes
      with no evidence of recurrence 12 months after surgery. In this report, we also
      discuss the clinical features and perioperative considerations in combination
      with a literature review. Our patient illustrates that clinicians should be aware
      of this rare clinical manifestation as the presenting feature of DISH in cervical
      spine. Surgical decompression through osteophytectomy is effective for patients
      who fail conservative treatment. 

PMID- 24729697
TI  - Outcomes of trochanteric femoral fractures treated with proximal femoral nail: an
      analysis of 100 consecutive cases.
AB  - PURPOSE: In this study, we aimed to report the results of a retrospective study
      carried out at our institute regarding cases of patients who had suffered
      proximal femoral fractures between January 2002 and February 2007, and who were
      treated with a proximal femoral nail. MATERIALS AND METHODS: One hundred
      consecutive cases were included in the study. A case documentation form was used
      to obtain intraoperative data including age, sex, mechanism of injury, type of
      fracture according to Association for Osteosynthesis/Association for the Study of
      Internal Fixation (AO/ASIF) classification and the American Society of
      Anesthesiologists' (ASA) physical status classification (ASA grade). Clinical and
      radiographic examinations were performed at the time of admission and at the 6th
      week; subsequent visits were organized on the 3rd month, 6th month, and 12th
      month, and in patients with longer follow-up and annually postoperatively. The
      Harris score of hip function was used, and any change in the position of the
      implants and the progress of the fracture union, which was determined
      radiologically, was noted. RESULTS: The mean age of the patients was 77.66 years
      (range: 37-98 years), and the sex distribution was 32 males and 68 females.
      Seventy-three fractures were reduced by closed means, whereas 27 needed limited
      open reduction. The mean follow-up time for the study group was 31.3 months
      (range: 12-75 months). Postoperative radiographs showed a near-anatomical
      fracture reduction in 78% of patients. The Harris hip score was negatively
      correlated with the ASA score and patient age. No cases of implant failure were
      observed. Three patients died before discharge (one due to pulmonary embolism,
      two due to cardiac arrest), and five patients died due to unrelated medical
      conditions within the first 3 months of the follow-up. CONCLUSION: Our study
      showed that proximal femoral nail is a reliable fixation with good fracture
      union, and it is not associated with major complications in any type of
      trochanteric femoral fracture.

PMID- 24729694
TI  - The genetics of Alzheimer's disease.
AB  - Alzheimer's disease (AD) is a complex and heterogeneous neurodegenerative
      disorder, classified as either early onset (under 65 years of age), or late onset
      (over 65 years of age). Three main genes are involved in early onset AD: amyloid
      precursor protein (APP), presenilin 1 (PSEN1), and presenilin 2 (PSEN2). The
      apolipoprotein E (APOE) E4 allele has been found to be a main risk factor for
      late-onset Alzheimer's disease. Additionally, genome-wide association studies
      (GWASs) have identified several genes that might be potential risk factors for
      AD, including clusterin (CLU), complement receptor 1 (CR1), phosphatidylinositol
      binding clathrin assembly protein (PICALM), and sortilin-related receptor
      (SORL1). Recent studies have discovered additional novel genes that might be
      involved in late-onset AD, such as triggering receptor expressed on myeloid cells
      2 (TREM2) and cluster of differentiation 33 (CD33). Identification of new AD
      related genes is important for better understanding of the pathomechanisms
      leading to neurodegeneration. Since the differential diagnoses of
      neurodegenerative disorders are difficult, especially in the early stages,
      genetic testing is essential for diagnostic processes. Next-generation sequencing
      studies have been successfully used for detecting mutations, monitoring the
      epigenetic changes, and analyzing transcriptomes. These studies may be a
      promising approach toward understanding the complete genetic mechanisms of
      diverse genetic disorders such as AD. 

PMID- 24729696
TI  - Vitamin D and neurocognitive function.
AB  - In recent years, emerging evidence has linked vitamin D not only to its known
      effects on calcium and bone metabolism, but also to many chronic illnesses
      involving neurocognitive decline. The importance of vitamin D3 in reducing the
      risk of these diseases continues to increase due to the fact that an increasing
      portion of the population in developed countries has a significant vitamin D
      deficiency. The older population is at an especially high risk for vitamin D
      deficiency due to the decreased cutaneous synthesis and dietary intake of vitamin
      D. Recent studies have confirmed an association between cognitive impairment,
      dementia, and vitamin D deficiency. There is a need for well-designed randomized
      trials to assess the benefits of vitamin D and lifestyle interventions in persons
      with mild cognitive impairment and dementia. 

PMID- 24729698
TI  - Examining the relationship between anxiety and depression and exacerbations of
      COPD which result in hospital admission: a systematic review.
AB  - OBJECTIVES: Exacerbations of chronic obstructive pulmonary disease (COPD) are the
      third largest cause of emergency hospital admissions in the UK. This systematic
      literature review explored the relationship between the hospitalization rates and
      the COPD comorbidities, anxiety, and depression. METHODS: The Centre for Research
      Dissemination's framework for systematic reviews was followed using search terms
      relating to COPD, anxiety, depression, and hospital admission. Papers identified
      were assessed for relevance and quality, using a suitable Critical Appraisal
      Skills Programme tool and Mixed Methods Assessment Tool. RESULTS: Twenty
      quantitative studies indicated that anxiety and depression led to a statistically
      significant increase in the likelihood of COPD patients being hospitalized. These
      comorbidities also led to an increased length of stay and a greater risk of
      mortality postdischarge. Other significant factors included lower Body-Mass
      Index, Airflow Obstruction, Dyspnea, and Exercise scores, female gender, lower
      socioeconomic status, poorer patient perceived quality of life, increased
      severity of lung function, and less improvement in dyspnea from admission to
      discharge. It was also highlighted that only 27%-33% of those with depression
      were being treated for it. Four qualitative studies revealed that patients saw
      anxiety and depression as a major factor that affected their ability to cope with
      and self-manage their condition. IMPLICATIONS: Findings from the systematic
      review have highlighted a need for better recognition and treatment of anxiety
      and depression amongst individuals with COPD. Ongoing research will develop and
      test strategies for promoting better management and self-management as a means of
      reducing hospital admissions.

PMID- 24729699
TI  - Clinical benefit of fixed-dose dual bronchodilation with glycopyrronium and
      indacaterol once daily in patients with chronic obstructive pulmonary disease: a
      systematic review.
AB  - BACKGROUND AND AIM: Long-acting bronchodilators are the preferred option for
      maintenance therapy of patients with chronic obstructive pulmonary disease
      (COPD). The aim of this review is to provide an overview of the clinical studies
      evaluating the clinical efficacy of the once-daily fixed-dose dual bronchodilator
      combination of indacaterol and glycopyrronium bromide in patients suffering from
      COPD. METHODS: This study comprised a systematic review of randomized controlled
      trials identified through systematic searches of different databases of published
      trials. RESULTS: Nine trials (6,166 participants) were included. Fixed-dose once
      daily indacaterol/glycopyrronium seems to be safe and well tolerated in patients
      with COPD. Compared with single therapy with other long-acting bronchodilators
      (indacaterol, glycopyrronium, and tiotropium) and fixed-combination long-acting
      beta2-agonist/inhaled corticosteroid (salmeterol/fluticasone twice daily), once
      daily fixed-dose indacaterol/glycopyrronium has clinically important effects on
      symptoms, including dyspnea score, health status, level of lung function, and
      rate of moderate or severe exacerbations in patients with moderate-to-very severe
      COPD (Global initiative for chronic Obstructive Lung Disease [GOLD] spirometric
      criteria). Furthermore, a very recent study has shown that fixed-dose
      indacaterol/glycopyrronium improves exercise endurance time compared with
      placebo, although no significant difference was observed between fixed-dose
      indacaterol/glycopyrronium and tiotropium. CONCLUSION: Fixed-dose
      indacaterol/glycopyrronium has clinically relevant effects on important COPD
      outcome measures and is, in general, superior to therapy with a single long
      acting bronchodilator (with or without inhaled corticosteroid) indicating long
      acting dual bronchodilation as a potential important maintenance therapeutic
      option for patients with symptomatic COPD, possibly also for the treatment of
      naive patients.

PMID- 24729700
TI  - Stem cell tracking using iron oxide nanoparticles.
AB  - Superparamagnetic iron oxide nanoparticles (SPIONs) are an exciting advancement
      in the field of nanotechnology. They expand the possibilities of noninvasive
      analysis and have many useful properties, making them potential candidates for
      numerous novel applications. Notably, they have been shown that they can be
      tracked by magnetic resonance imaging (MRI) and are capable of conjugation with
      various cell types, including stem cells. In-depth research has been undertaken
      to establish these benefits, so that a deeper level of understanding of stem cell
      migratory pathways and differentiation, tumor migration, and improved drug
      delivery can be achieved. Stem cells have the ability to treat and cure many
      debilitating diseases with limited side effects, but a main problem that arises
      is in the noninvasive tracking and analysis of these stem cells. Recently,
      researchers have acknowledged the use of SPIONs for this purpose and have set out
      to establish suitable protocols for coating and attachment, so as to bring MRI
      tracking of SPION-labeled stem cells into common practice. This review paper
      explains the manner in which SPIONs are produced, conjugated, and tracked using
      MRI, as well as a discussion on their limitations. A concise summary of recently
      researched magnetic particle coatings is provided, and the effects of SPIONs on
      stem cells are evaluated, while animal and human studies investigating the role
      of SPIONs in stem cell tracking will be explored. 

PMID- 24729701
TI  - Adenosine diphosphate-decorated chitosan nanoparticles shorten blood clotting
      times, influencing the structures and varying the mechanical properties of the
      clots.
AB  - Chitosan nanoparticles (NPs) decorated with adenosine diphosphate (ADP) (ANPs) or
      fibrinogen (FNPs) were used to fabricate hemostatic NPs that can shorten blood
      clotting time and prevent severe local hemorrhage. The structure and mechanical
      properties of the blood clot induced with ANP (clot/ANP) or FNP (clot/FNP) were
      also investigated. The NPs, ANPs, and FNPs, which had particle sizes of 245.1 +/-
      14.0, 251.0 +/- 9.8, and 326.5 +/- 14.5 nm and zeta potentials of 24.1 +/- 0.5,
      20.6 +/- 1.9, and 15.3 +/- 1.5 mV (n=4), respectively, were fabricated by ionic
      gelation and then decorated with ADP and fibrinogen. The zeta potentials and
      Fourier transform infrared (FTIR) spectroscopy of the NPs confirmed that their
      surfaces were successfully coated with ADP and fibrinogen. The scanning electron
      microscope (SEM) micrographs of the structure of the clot induced with
      "undecorated" chitosan NPs (clot/NP), clot/ANP, and clot/FNP (at 0.05 wt%) were
      different, after citrated bloods had been recalcified by a calcium chloride
      solution containing NPs, ANPs, or FNPs. This indicated that many NPs adhered on
      the membrane surfaces of red blood cells, that ANPs induced many platelet
      aggregates, and that FNPs were incorporated into the fibrin network in the clots.
      Measurements of the blood clotting times (Tc) of blood clot/NPs, clot/ANPs, and
      clot/FNPs, based on 90% of ultimate frequency shifts measured on a quartz crystal
      microbalance (QCM), were significantly (P<0.05) (n=4) shorter than that of a clot
      induced by a phosphate-buffered solution (PBS) (clot/PBS) (63.6% +/- 3.1%, 48.3%
      +/- 6.2%, and 63.2% +/- 4.7%, respectively). The DeltaF2 values in the spectra of
      frequency shifts associated with the propagation of fibrin networks in the
      clot/ANPs and clot/FNPs were significantly lower than those of clot/PBS.
      Interestingly, texture profile analysis of the compressional properties showed
      significantly lower hardness and compressibility in clot/NPs and clot/ANPs
      (P<0.05 or better) (n=4) compared with clot/PBS and clot/FNPs. Accordingly, among
      the hemostatic NPs, ANP substantially reduced blood clotting times, DeltaF2
      values, and compression flow properties of the clot. Hence, ANPs have potential
      applications for preventing severe local hemorrhage.

PMID- 24729702
TI  - Preparation of redispersible liposomal dry powder using an ultrasonic spray
      freeze-drying technique for transdermal delivery of human epithelial growth
      factor.
AB  - In this work, an ultrasonic spray freeze-drying (USFD) technique was used to
      prepare a stable liposomal dry powder for transdermal delivery of recombinant
      human epithelial growth factor (rhEGF). Morphology, particle size, entrapment
      efficiency, in vitro release, and skin permeability were systematically compared
      between rhEGF liposomal dry powder prepared using USFD and that prepared using a
      conventional lyophilization process. Porous and spherical particles with high
      specific area were produced under USFD conditions. USFD effectively avoided
      formation of ice crystals, disruption of the bilayer structure, and drug leakage
      during the liposome drying process, and maintained the stability of the rhEGF
      liposomal formulation during storage. The reconstituted rhEGF liposomes prepared
      from USFD powder did not show significant changes in morphology, particle size,
      entrapment efficiency, or in vitro release characteristics compared with those of
      rhEGF liposomes before drying. Moreover, the rhEGF liposomal powder prepared with
      USFD exhibited excellent enhanced penetration in ex vivo mouse skin compared with
      that for powder prepared via conventional lyophilization. The results suggest
      that ultrasonic USFD is a promising technique for the production of stable
      protein-loaded liposomal dry powder for application to the skin. 

PMID- 24729703
TI  - Pharmacological and toxicological effects of co-exposure of human gingival
      fibroblasts to silver nanoparticles and sodium fluoride.
AB  - BACKGROUND: Silver nanoparticles (AgNPs) and fluoride (F) are pharmacological
      agents widely used in oral medicine and dental practice due to their anti
      microbial/anti-cavity properties. However, risks associated with the co-exposure
      of local cells and tissues to these xenobiotics are not clear. Therefore, we have
      evaluated the effects of AgNPs and F co-exposure on human gingival fibroblast
      cells. METHODS: Human gingival fibroblast cells (CRL-2014) were exposed to AgNPs
      and/or F at different concentrations for up to 24 hours. Cellular uptake of AgNPs
      was examined by transmission electron microscopy. Downstream inflammatory effects
      and oxidative stress were measured by real-time quantitative polymerase chain
      reaction (PCR) and reactive oxygen species (ROS) generation. Cytotoxicity and
      apoptosis were measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium
      bromide (MTT) assay and real-time quantitative PCR and flow cytometry,
      respectively. Finally, the involvement of mitogen-activated protein kinases
      (MAPK) was studied using Western blot. RESULTS: We found that AgNPs penetrated
      the cell membrane and localized inside the mitochondria. Co-incubation
      experiments resulted in increased oxidative stress, inflammation, and apoptosis.
      In addition, we found that co-exposure to both xenobiotics phosphorylated MAPK,
      particularly p42/44 MAPK. CONCLUSION: A combined exposure of human fibroblasts to
      AgNPs and F results in increased cellular damage. Further studies are needed in
      order to evaluate pharmacological and potentially toxicological effects of AgNPs
      and F on oral health.

PMID- 24729704
TI  - Fracture toughness of titanium-cement interfaces: effects of fibers and loading
      angles.
AB  - Ideal implant-cement or implant-bone interfaces are required for implant fixation
      and the filling of tissue defects created by disease. Micron- to nanosize
      osseointegrated features, such as surface roughness, fibers, porosity, and
      particles, have been fused with implants for improving the osseointegration of an
      implant with the host tissue in orthopedics and dentistry. The effects of fibers
      and loading angles on the interface fracture toughness of implant-cement
      specimens with and without fibers at the interface are not yet known. Such
      studies are important for the design of a long-lasting implant for orthopedic
      applications. The goal of this study was to improve the fracture toughness of an
      implant-cement interface by deposition of micron- to nanosize fibers on an
      implant surface. There were two objectives in the study: 1) to evaluate the
      influence of fibers on the fracture toughness of implant-cement interfaces with
      and without fibers at the interfaces, and 2) to evaluate the influence of loading
      angles on implant-cement interfaces with and without fibers at the interfaces.
      This study used titanium as the implant, poly(methyl methacrylate) (PMMA) as
      cement, and polycaprolactone (PCL) as fiber materials. An electrospinning unit
      was fabricated for the deposition of PCL unidirectional fibers on titanium (Ti)
      plates. The Evex tensile test stage was used to determine the interface fracture
      toughness (KC) of Ti-PMMA with and without PCL fibers at 0 degrees , 45 degrees ,
      and 90 degrees  loading angles, referred to in this article as tension, mixed,
      and shear tests. The study did not find any significant interaction between fiber
      and loading angles (P>0.05), although there was a significant difference in the
      KC means of Ti-PMMA samples for the loading angles (P<0.05). The study also found
      a significant difference in the KC means of Ti-PMMA samples with and without
      fibers (P<0.05). The results showed that the addition of the micron- to nanosize
      PCL fibers on Ti improved the quality of the Ti-PMMA union. The results of the
      study are essential for fatigue testing and finite-element analysis of implant
      cement interfaces to evaluate the performance of orthopedic and orthodontic
      implants. 

PMID- 24729705
TI  - Lateral flow test strip based on colloidal selenium immunoassay for rapid
      detection of melamine in milk, milk powder, and animal feed.
AB  - Although high melamine (MEL) intake has been proven to cause serious health
      problems, MEL is sometimes illegally added to milk products and animal feed,
      arousing serious food safety concerns. A satisfactory method of detecting MEL in
      onsite or in-home testing is in urgent need of development. This work aimed to
      explore a rapid, convenient, and cost-effective method of identifying MEL in milk
      products or other food by colloidal selenium-based lateral flow immunoassay.
      Colloidal selenium was synthesized by L-ascorbic acid to reduce seleninic acid at
      room temperature. After conjugation with a monoclonal antibody anti-MEL, a test
      strip was successfully prepared. The detection limit of the test strip reached
      150 MUg/kg, 1,000 MUg/kg, and 800 MUg/kg in liquid milk, milk powder, and animal
      feed, respectively. No cross-reactions with homologues cyanuric acid,
      cyanurodiamide, or ammelide were found. Moreover, the MEL test strip can remain
      stable after storage for 1 year at room temperature. Our results demonstrate that
      the colloidal selenium MEL test strip can detect MEL in adulterated milk products
      or animal feed conveniently, rapidly, and sensitively. In contrast with a
      colloidal gold MEL test strip, the colloidal selenium MEL test strip was easy to
      prepare and more cost-efficient. 

PMID- 24729706
TI  - Preparation and in vitro/in vivo characterization of enteric-coated nanoparticles
      loaded with the antihypertensive peptide VLPVPR.
AB  - Our previous study revealed that the peptide Val-Leu-Pro-Val-Pro-Arg (VLPVPR),
      which was prepared using deoxyribonucleic acid recombinant technology,
      effectively decreased the blood pressure of spontaneous hypertensive rats;
      however, the effect only lasts 6 hours, likely due to its low absorption in the
      gastrointestinal tract. To overcome this problem, the purpose of this study was
      to characterize (methoxy-polyethylene glycol)-b-poly(D,L-lactide-co-glycolide)-b
      poly(L-lysine) nanoparticles as in vitro and in vivo carriers for the effective
      delivery of VLPVPR. In our study, the VLPVPR nanoparticles were prepared using a
      double emulsion method, coated with Eudragit S100, and freeze-dried to produce
      enteric-coated nanoparticles. The optimized parameters from the double emulsion
      method was obtained from orthogonal experiments, including drug loading (DL) and
      encapsulated ratio (ER) at 6.12% and 86.94%, respectively, and the average
      particle size was below 100 nm. The release experiment demonstrated that the
      nanoparticles were sensitive to pH: almost completely released at pH 7.4 after 8
      hours, but demonstrated much less release at pH 4.5 or pH 1.0 in the same amount
      of time. Therefore, the nanoparticles are suitable for enteric release. In vivo
      compared with the untreated group, the medium and high doses of orally
      administered VLPVPR nanoparticles reduced blood pressure for more than 30 hours,
      demonstrating that these nanoparticles have long-lasting and significant
      antihypertensive effects in spontaneously hypertensive rats. 

PMID- 24729707
TI  - Synthesis, characterization, and evaluation of antibacterial effect of Ag
      nanoparticles against Escherichia coli O157:H7 and methicillin-resistant
      Staphylococcus aureus (MRSA).
AB  - Silver nanoparticles (AgNPs) have been shown great interest because of their
      potential antibacterial effect. Recently, this has been increased due to
      resistance in some pathogenic bacteria strains to conventional antibiotics, which
      has initiated new studies to search for more effective treatments against
      resistant microorganisms. For these reasons, AgNPs have become an important
      approach for applications in nanobiotechnology in the development of antibiotic
      treatment of different bacterial infections. This study was aimed at synthesizing
      AgNPs using cysteine as a reducer agent and cetyl-tri-methyl-ammonium bromide as
      a stabilizer in order to obtain more efficient treatment against the pathogen
      bacteria Escherichia coli O157:H7. These AgNPs were characterized through UV-Vis
      spectroscopy, transmission electron microscopy, and dynamic light scattering.
      From these analyses, formation of spherical nanoparticles with an average size of
      55 nm was confirmed. Finally, minimal inhibitory concentration (MIC) and minimal
      bactericide concentration (MBC) of these AgNPs against pathogenic strains E. coli
      O157:H7 and methicillin-resistant Staphylococcus aureus (MRSA) were determined in
      both solid and liquid media. MIC and MBC values were around 0.25 MUg/mL and 1
      MUg/mL, respectively. These parameters were comparable to those reported in the
      literature and were even more effective than other synthesized AgNPs. 

PMID- 24729708
TI  - Emerging therapeutic options for acute migraine: focus on the potential of
      lasmiditan.
AB  - The serotonin receptor agonist triptan drugs (5-HT1B/1D receptor agonists) have
      been in use for over 20 years in the abortive management of migraine. Although
      clearly effective, their ability to produce vasoconstriction in cerebral and
      coronary arteries, thought to be mediated by their high affinity for the 5-HT1B
      receptor, has been a limitation to their use in certain patient populations.
      Variable potency triptan binding at the 5-HT1F receptor occurs in addition to
      binding at the 5-HT1B and 5-HT1D receptors. A more selective serotonin agonist
      without 5-HT1B-mediated vasoconstriction might prove efficacious yet safer. The 5
      HT1F receptor has been targeted as a site of action for such a drug. In
      experimental models, 5-HT1F receptor agonists have been shown to block neurogenic
      inflammation and c-Fos expression in neural tissue and, as well, show no evidence
      of vasoconstriction in vascular tissue models in vitro. In clinical trials,
      efficacy in the abortive management of migraine has been established. Lasmiditan
      (LY573144), a selective 5-HT1F receptor agonist (K1=2.21 MUM), showed efficacy in
      its primary endpoint, with a 2-hour placebo-subtracted headache response of
      28.8%, though with frequent reports of dizziness, paresthesias, and vertigo.
      Study results support an emerging central neuronal mechanism of migraine
      pathophysiology. This review traces the history and use of 5-HT1F receptor
      agonists, now referred to as neurally acting anti-migraine agents in migraine
      management. 

PMID- 24729709
TI  - Anterior capsulotomy improves persistent developmental stuttering with a
      psychiatric disorder: a case report and literature review.
AB  - Stuttering is characterized by disrupted fluency of verbal expression, and occurs
      mostly in children. Persistent developmental stuttering (PDS) may occur in
      adults. Reports of the surgical management of PDS are limited. Here we present
      the case of a 28-year-old man who had had PDS since the age of 7 years, was
      diagnosed with depression and anxiety disorder at the age of 24 years, and had
      physical concomitants. He underwent a bilateral anterior capsulotomy 4 years
      after the diagnosis. Over one year of follow-up, his physical concomitants
      resolved, and significant improvements in his psychiatric disorders and PDS were
      observed. To the best of our knowledge, this is the first report of simultaneous
      improvement in a patient's PDS and psychiatric disorder after a bilateral
      anterior capsulotomy. 

PMID- 24729710
TI  - Effectiveness of methylphenidate as augmentation therapy after failure of
      adjunctive neuromodulation for patients with treatment-refractory bipolar
      depression: a case report.
AB  - Adjunctive use of methylphenidate, a central stimulant, has been considered as a
      potential therapeutic choice for patients with refractory unipolar, geriatric, or
      bipolar depression, and depression secondary to medical illness. We present a
      case of bipolar depression in which the patient responded significantly to
      augmentation with methylphenidate, without any side effects, after failure of
      adjunctive repetitive transcranial magnetic stimulation and electroconvulsive
      therapy. Mr U, a 56-year-old man with bipolar I disorder, had melancholic
      symptoms during his sixth episode of bipolar depression. After failure of
      repetitive transcranial magnetic stimulation and electroconvulsive therapy, he
      was treated with fluoxetine 80 mg/day, duloxetine 360 mg/day, mirtazapine 60
      mg/day, and sodium valproate 1,000 mg/day, with no improvement. We added
      methylphenidate at a dose of 10 mg/day for one week, which resulted in mild
      clinical improvement, and then methylphenidate extended-release 20 mg/day for one
      week, with significant clinical improvement. He tolerated his medications well.
      His clinical recovery was stable over one year. The patient's antidepressants and
      methylphenidate were gradually tapered and finally discontinued after one year
      with no withdrawal syndrome. To date, he remains well on sodium valproate as
      monotherapy and is being followed up at our bipolar department. This case
      suggests that methylphenidate augmentation might be a therapeutic option when
      treating highly treatment-resistant patients with bipolar depression, even if
      they had not responded to adjunctive neuromodulation. In these clinical
      situations, physicians might be interested in prescribing methylphenidate because
      of its efficacy and safety. 

PMID- 24729711
TI  - Prediction and prevention of the first psychotic episode: new directions and
      opportunities.
AB  - In the last few decades, substantial research has focused on the possibility of
      early detection and prevention of the first psychotic episode in young
      individuals at risk of developing this mental disturbance; however, unresolved
      clinical and ethical issues still call for further investigations. New
      perspectives and opportunities may come from the identification of selective
      psychopathological and instrumental markers linking the appearance of subtle
      psychotic symptoms with the clinical outcome of specific mental pathologies.
      Furthermore, empirically derived algorithms and risk staging models should
      facilitate the identification of targeted prevention therapies, possibly
      improving the efficacy of well-tolerated therapeutic approaches, such as
      psychological interventions and natural compound supplementations. To date, the
      collected evidence on the efficacy and tolerability of pharmacological prevention
      therapies raises more doubts than hopes. A very early detection of risk and
      appropriate symptomatic pattern classifications may provide a chance to better
      match prevention strategies with the development of psychosis. 

PMID- 24729712
TI  - Neurogenic orthostatic hypotension in Parkinson's disease: evaluation,
      management, and emerging role of droxidopa.
AB  - Neurogenic orthostatic hypotension (nOH) is due to failure of the autonomic
      nervous system to regulate blood pressure in response to postural changes due to
      an inadequate release of norepinephrine, leading to orthostatic hypotension and
      supine hypertension. nOH is common in Parkinson's disease (PD). Prevalence varies
      throughout the course of PD, ranging from 40% to 60%, and resulting in
      symptomatic nOH in approximately half. Symptomatic nOH, including
      lightheadedness, can limit daily activities and lead to falls. Symptomatic nOH
      can also limit therapeutic options for treating PD motor symptoms. Clinical
      evaluation should routinely include symptom assessment and blood pressure
      measurement of supine, sitting, and 3-minute standing; 24-hour ambulatory blood
      pressure monitoring can also be helpful. Non-pharmacological management of
      symptomatic nOH involves education, physical maneuvers, and adequate hydration.
      Current pharmacological treatment of symptomatic nOH includes salt supplement,
      fludrocortisone, midodrine, pyridostigmine, and other empiric medications.
      Despite these options, treatment of symptomatic nOH remains suboptimal, often
      limited by severe increases in supine blood pressure. Droxidopa, an oral prodrug
      converted by decarboxylation to norepinephrine, is a promising therapeutic option
      for symptomatic nOH in PD, improving symptoms of nOH, daily activities, falls,
      and standing systolic blood pressure in several recent trials. These trials
      demonstrated short-term efficacy and tolerability, with comparable increases in
      standing and supine blood pressures. Longer-term studies are ongoing to confirm
      durability of treatment effect. 

PMID- 24729714
TI  - Exploring physical health perceptions, fatigue and stress among health care
      professionals.
AB  - Nurses, midwives, and paramedics are exposed to high degrees of job demand, which
      impacts health status and job satisfaction. The aim of this study was to explore
      the experiences and perceptions of health with a group of nurses, midwives and
      paramedics in Australia. Specifically, this paper reveals the findings related to
      the dataset on physical health. In this regard, the researchers sought to explore
      the relationship between physical health and job satisfaction, and the
      relationship between health status and stress levels. The study adopted a mixed
      methodology and used two methods for data collection: one-on-one interviews
      exploring the relationship between physical health and job satisfaction, and a
      survey questionnaire focusing on self-rated stress management. The individual
      interviews were conducted for further exploration of the participants' responses
      to the survey. There were 24 health care participants who were drawn from
      metropolitan and regional Australia. The findings revealed participants: had a
      desire to increase their physical activity levels; had different perspectives of
      physical health from those recommended by government guidelines; and viewed
      physical health as important to job satisfaction, yet related to stress and
      fatigue. 

PMID- 24729713
TI  - Unmet needs in the management of acute myocardial infarction: role of novel
      protease-activated receptor-1 antagonist vorapaxar.
AB  - Platelet activation with subsequent aggregation is a complex process leading to
      thrombus formation, which remains a key component for atherothrombotic
      manifestations, in particular myocardial infarction. Therefore, antiplatelet
      therapies are pivotal for the treatment of these patients. Current oral
      antiplatelet therapies used for secondary prevention of ischemic recurrences
      include aspirin and adenosine diphosphate P2Y12 platelet-receptor antagonists.
      However, despite these therapies, patients who have experienced a myocardial
      infarction remain at risk for ischemic recurrences. Therefore, more aggressive
      secondary prevention measures have been an area of research, including
      identifying additional targets modulating platelet-activation and -aggregation
      processes. Among these, thrombin-mediated platelet activation via protease
      activated receptors (PARs) has been subject to extensive clinical investigation.
      Several PAR-1 receptor antagonists have been developed. However, vorapaxar is the
      only one that has completed large-scale clinical investigation. The present
      manuscript will provide an overview on the role of thrombin-mediated signaling,
      the impact of PAR-1 blockade with vorapaxar on ischemic and bleeding outcomes,
      and the potential role for vorapaxar in clinical practice. 

PMID- 24729715
TI  - Role of capecitabine in treating metastatic colorectal cancer in Chinese
      patients.
AB  - The China Food and Drug Administration approved the use of capecitabine in
      patients with metastatic colorectal cancer (mCRC) in 2004. This paper reviews the
      available information of capecitabine in Chinese patients with mCRC, focusing on
      its effectiveness and safety against mCRC. Identification of all eligible studies
      was made by searching the PubMed and Wanfang database from 2000 to 2013.
      Published data examining various aspects of clinical response and tolerability
      with capecitabine alone or in combination with other chemotherapeutic or
      biological agents for first- and second-line mCRC were examined. Capecitabine and
      its combination displayed high efficacy in Chinese patients with mCRC. Toxicities
      are generally manageable, and elderly patients can tolerate capecitabine well. 

PMID- 24729716
TI  - Primary concomitant EGFR T790M mutation predicted worse prognosis in non-small
      cell lung cancer patients.
AB  - PURPOSE: We performed this analysis to improve the understanding of the
      clinicopathological characteristics and clinical outcome of non-small cell lung
      cancer (NSCLC) patients harboring the primary epidermal growth factor receptor
      (EGFR) T790M mutation along with activating EGFR mutation. METHODS: Resected
      tumors from 1903 NSCLC patients were analyzed for mutation in EGFR, as well as
      KRAS (Kirsten rat sarcoma viral oncogene homolog), BRAF (v-raf murine sarcoma
      viral oncogene homolog B), HER2 (human epidermal growth factor 2), PIK3CA
      (phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha), and
      EML4 (echinoderm microtubule associated protein like 4)-ALK (anaplastic lymphoma
      receptor tyrosine kinase) fusion. Fluorescence in situ hybridization was
      performed to define EGFR and c-MET (met proto-oncogene gene amplification.
      Expression of PIK3CA and p-Akt (phosphorylated protein kinase B) were tested
      using immunohistochemistry. Clinical and pathological data, including sex, age at
      diagnosis, stage, tumor differentiation, smoking history, histological subtype,
      relapse-free and overall survival, were further analyzed. RESULTS: In all, 16
      NSCLC patients were found to harbor primary EGFR T790M mutation, including 14
      adenocarcinomas and two adenosquamous carcinomas, accounting for 2.04% of all the
      EGFR mutant cases and 0.84% of the total. No c-MET amplification was found to
      coexist with primary EGFR T790M. Fewer EGFR copy-number variations were found in
      samples harboring EGFR T790M mutations compared with those in patients with exon
      19 deletions and L858R. Overall survival was significantly shorter for patients
      harboring EGFR T790M mutation than it was for patients with exon 19 deletions
      (logrank P=0.008). When taking patients harboring EGFR L858R or exon 19 deletions
      as one group, the overall survival was also significantly longer than that in
      patients with T790M mutation (logrank P=0.012). There was no significant
      difference in relapse-free survival among three subgroups of patients.
      CONCLUSION: Our study described the clinicopathological and molecular
      characteristics of NSCLC patients harboring primary EGFR T790M mutations. Its
      value of being a predictor for worse prognosis was established. Primary EGFR
      T790M mutation is a rare event in NSCLC cases, but the therapeutic strategies for
      this subtype of patients should be precisely considered.

PMID- 24729717
TI  - Link between vitamin D and airway remodeling.
AB  - In the last decade, many epidemiologic studies have investigated the link between
      vitamin D deficiency and asthma. Most studies have shown that vitamin D
      deficiency increases the risk of asthma and allergies. Low levels of vitamin D
      have been associated with asthma severity and loss of control, together with
      recurrent exacerbations. Remodeling is an early event in asthma described as a
      consequence of production of mediators and growth factors by inflammatory and
      resident bronchial cells. Consequently, lung function is altered, with a decrease
      in forced expiratory volume in one second and exacerbated airway
      hyperresponsiveness. Subepithelial fibrosis and airway smooth muscle cell
      hypertrophy are typical features of structural changes in the airways. In animal
      models, vitamin D deficiency enhances inflammation and bronchial anomalies. In
      severe asthma of childhood, major remodeling is observed in patients with low
      vitamin D levels. Conversely, the antifibrotic and antiproliferative effects of
      vitamin D in smooth muscle cells have been described in several experiments. In
      this review, we briefly summarize the current knowledge regarding the
      relationship between vitamin D and asthma, and focus on its effect on airway
      remodeling and its potential therapeutic impact for asthma. 

PMID- 24729718
TI  - Meningococcal serogroups A, C, W-135, and Y tetanus toxoid conjugate vaccine: a
      new conjugate vaccine against invasive meningococcal disease.
AB  - Invasive meningococcal disease is a serious infection that occurs worldwide. It
      is caused by Neisseria meningitidis, of which six serogroups (A, B, C, W-135, X,
      and Y) are responsible for most infections. The case fatality rate of
      meningococcal disease remains high and can lead to significant sequelae.
      Vaccination remains the best strategy to prevent meningococcal disease.
      Polysaccharide vaccines were initially introduced in the late 1960s but their
      limitations (poor immunogenicity in infants and toddlers and hyporesponsiveness
      after repeated doses) have led to the development and use of meningococcal
      conjugate vaccines, which overcome these limitations. Two quadrivalent conjugated
      meningococcal vaccines - MenACWY-DT (Menactra((r))) and MenACWY-CRM197
      (Menveo((r))) - using diphtheria toxoid or a mutant protein, respectively, as
      carrier proteins have already been licensed in the US. Recently, a quadrivalent
      meningococcal vaccine conjugated to tetanus toxoid (MenACWY-TT; Nimenrix((r)))
      was approved for use in Europe in 2012. The immunogenicity of MenACWY-TT, its
      reactogenicity and safety profile, as well as its coadministration with other
      vaccines are discussed in this review. Clinical trials showed that MenACWY-TT was
      immunogenic in children above the age of 12 months, adolescents, and adults, and
      has an acceptable reactogenicity and safety profile. Its coadministration with
      several other vaccines that are commonly used in children, adolescents, and
      adults did not affect the immunogenicity of MenACWY-TT or the coadministered
      vaccine, nor did it affect its reactogenicity and safety. Other studies are now
      ongoing in order to determine the immunogenicity, reactogenicity, and safety of
      MenACWY-TT in infants from the age of 6 weeks. 

PMID- 24729719
TI  - Economic implications of using bendamustine, alemtuzumab, or chlorambucil as a
      first-line therapy for chronic lymphocytic leukemia in the US: a cost
      effectiveness analysis.
AB  - BACKGROUND: The objective of this analysis was to evaluate the cost-effectiveness
      of using bendamustine versus alemtuzumab or bendamustine versus chlorambucil as a
      first-line therapy in patients with Binet stage B or C chronic lymphocytic
      leukemia (CLL) in the US. METHODS: A discrete event simulation of the disease
      course of CLL was developed to evaluate the economic implications of single-agent
      treatment with bendamustine, alemtuzumab, or chlorambucil, which are indicated
      for a treatment-naive patient population with Binet stage B or C CLL. Data from
      clinical trials were used to create a simulated patient population, risk
      equations for progression-free survival and survival post disease progression,
      response rates, and rates of adverse events. Costs from a US health care payer
      perspective in 2012 US dollars, survival (life years), and quality-adjusted life
      years (QALYs) were estimated over a patient's lifetime; all were discounted at 3%
      per year. RESULTS: Compared with alemtuzumab, bendamustine was considered to be a
      dominant treatment providing greater benefit (6.10 versus 5.37 life years and
      4.02 versus 3.45 QALYs) at lower cost ($78,776 versus $121,441). Compared with
      chlorambucil, bendamustine was associated with higher costs ($78,776 versus
      $42,337) but with improved health outcomes (6.10 versus 5.21 life years and 4.02
      versus 3.30 QALYs), resulting in incremental cost-effectiveness ratios of $40,971
      per life year gained and $50,619 per QALY gained. CONCLUSION: Bendamustine is
      expected to provide cost savings and greater health benefit than alemtuzumab in
      treatment-naive patients with CLL. Furthermore, it can be considered as a cost
      effective treatment providing health benefits at an acceptable cost versus
      chlorambucil in the US.

PMID- 24729720
TI  - Economic and humanistic burden of illness in generalized anxiety disorder: an
      analysis of patient survey data in Europe.
AB  - BACKGROUND: Whilst studies suggest that generalized anxiety disorder (GAD)
      represents a considerable health care burden in Europe, there is a paucity of
      published evidence. This study investigated the burden of illness associated with
      GAD across five European countries (France, Germany, Italy, Spain, and the UK).
      METHODS: Information from the 2008 European National Health and Wellness Survey
      database was analyzed. Bivariate, multivariate, and cost analyses were used to
      compare patients with GAD and propensity-matched controls. RESULTS: Compared with
      non-GAD controls, patients with GAD had more comorbidities and were more likely
      to smoke but less likely to be employed, use alcohol, or take exercise. They also
      had significantly worse health-related quality of life, and significantly greater
      work impairment and resource use, which increased as GAD severity increased.
      Within-country analyses demonstrated results similar to those for the five
      European countries overall, with the largest differences in resource use between
      patients with GAD and non-GAD controls documented in France and Germany. The
      average mean differences in direct costs were relatively small between the GAD
      groups and controls; however, indirect costs differed substantially. Costs were
      particularly high in Germany, mainly due to higher salaries leading to higher
      costs associated with absence from work. The limitation of this study was that
      the data were from a self-reported Internet survey, making them subject to
      reporting bias and possibly sample bias. CONCLUSION: Across all five European
      countries, GAD had a significant impact on work impairment, resource use, and
      economic costs, representing a considerable individual and financial burden that
      increased with severity of disease. These data may help us to understand better
      the burden and costs associated with GAD.

PMID- 24729721
TI  - Economic burden of torture for a refugee host country: development of a model and
      presentation of a country case study.
AB  - BACKGROUND: Torture is an important social and political problem worldwide that
      affects millions of people. Many host countries give victims of torture the
      status of refugee and take care of them as far as basic needs; health care,
      professional reinsertion, and education. Little is known about the costs of
      torture. However, this knowledge could serve as an additional argument for the
      prevention and social mobilization to fight against torture and to provide a
      powerful basis of advocacy for rehabilitation programs and judiciary claims.
      OBJECTIVES: Development of a model for estimating the economic costs of torture
      and applying the model to a specific country. METHODS: The estimation of the
      possible prevalence of victims of torture was based on a review of the
      literature. The identification of the socioeconomic factors to be considered was
      done by analogy with various health problems. The estimation of the loss of the
      productivity and of the economic burden of disease related to torture was done
      through the human capital approach and the component technique analysis. CASE
      STUDY: The model was applied to the situation in Switzerland of estimated torture
      victims Switzerland is confronted with. RESULTS: When applied to the case study,
      the direct costs - such as housing, food, and clothing - represent roughly 130
      million Swiss francs (CHF) per year; whereas, health care costs amount to 16
      million CHF per year, and the costs related to education of young people to 34
      million CHF per year. Indirect costs, namely those costs related to the loss of
      the productivity of direct survivors of torture, have been estimated to one-third
      of 1 billion CHF per year. This jumps to 10,073,419,200 CHF in the loss of
      productivity if one would consider 30 years of loss per survivor. CONCLUSION: Our
      study shows that a rough estimation of the costs related to torture is possible
      with some prerequisites, such as access to social and economic indicators at the
      country level.

PMID- 24729722
TI  - From depolarization-dependent contractions in gastrointestinal smooth muscle to
      aortic pulse-synchronized contractions.
AB  - For decades, it was believed that the diameter of gastrointestinal smooth muscle
      cells is sufficiently narrow, and that the diffusion of calcium across the plasma
      membrane is sufficient, to support contractile activity. Thus, depolarization
      triggered release of intracellular calcium was not believed to be operative in
      gastrointestinal smooth muscle. However, after the incubation of muscle segments
      in solutions devoid of calcium and containing the calcium chelator ethylene
      glycol tetraacetic acid, an alternative electrical event occurred that was
      distinct from normal slow waves and spikes. Subsequently, it was demonstrated in
      gastrointestinal smooth muscle segments that membrane depolarization associated
      with this alternative electrical event triggered rhythmic contractions by release
      of intracellular calcium. Although this concept of depolarization-triggered
      calcium release was iconoclastic, it has now been demonstrated in multiple
      gastrointestinal smooth muscle preparations. On the basis of these observations,
      we investigated whether a rhythmic electrical and mechanical event would occur in
      aortic smooth muscle under the same calcium-free conditions. The incubation of
      aortic segments in a solution with no added calcium plus ethylene glycol
      tetraacetic acid induced a fast electrical event without corresponding tension
      changes. On the basis of the frequency of these fast electrical events, we
      pursued, contrary to what has been established dogma for more than three
      centuries, the question of whether the smooth muscle wall of the aorta undergoes
      rhythmic activation during the cardiac cycle. As with depolarization-triggered
      contractile activity in gastrointestinal smooth muscle, it was "well known" that
      rhythmic activation of the aorta does not occur in synchrony with the heartbeat.
      In a series of experiments, however, it was demonstrated that rhythmic
      contractions occur in the aortic wall in synchrony with the heartbeat and share a
      common pacemaker with the heart. We conclude that important observations in the
      vascular system became derivative from those in the gastrointestinal system. The
      challenging of scientific dogma potentially leads to the expansion of our
      fundamental knowledge base. 

PMID- 24729723
TI  - Lupus nephritis flare in young patients: relapse or nonadherence to treatment?
AB  - PURPOSE: Adherence is a challenging issue in the treatment of systemic lupus
      erythematosus. Nonadherence has been widely addressed in patients with lupus and
      must be detected quickly to prevent severe complications. The cases we present
      illustrate the importance of adherence in young adults. CASE 1: A 23-year-old
      Spanish woman diagnosed with severe lupus nephritis 8 years previously achieved
      renal remission after immunosuppressive treatment with corticosteroids and
      cyclophosphamide. Three years later, she developed a renal flare. Her treatment
      was intensified, and rituximab and mycophenolate mofetil were added. One year
      later, she was readmitted for a new renal flare. A blood test revealed no
      detectable levels of mycophenolic acid, and the patient admitted she had not
      taken her treatment correctly. Treatment was resumed. Four years later, the
      patient remains in remission. CASE 2: A 19-year-old Spanish woman was diagnosed
      with nephrotic syndrome due to lupus nephritis. She achieved complete remission
      after treatment with corticosteroids and cyclophosphamide followed by
      mycophenolate mofetil. Two years later, she developed a severe renal relapse that
      was treated with corticosteroids, cyclophosphamide, and rituximab. The response
      to treatment was good. Mycophenolic acid was undetectable in blood. The patient
      admitted that she had often missed doses before this relapse. The renal response
      has been maintained since she resumed her previous medications 2 years ago.
      CONCLUSION: We conclude that the frequent and severe relapses of lupus nephritis
      observed in young patients may actually be due to nonadherence rather than to
      refractory disease. Our cases are typical examples of nonadherence that were
      discovered after a detailed interview with the patients and their families. We
      emphasize the need for clinical suspicion of nonadherence when caring for young
      adults with lupus.

PMID- 24729724
TI  - The pleiotropic effects of the hydroxy-methyl-glutaryl-CoA reductase inhibitors
      in renal disease.
AB  - It is well known that statins exert their main effect by inhibiting cholesterol
      synthesis through the inhibition of the 3-hydroxy-3-methyl-glutaryl-CoA reductase
      enzyme. The pleiotropic effects of statins, which are independent of their
      inhibition of cholesterol synthesis, have explained many of the beneficial
      effects of these drugs in a variety of disorders such as malignancies, infection,
      and sepsis, as well as in cardiovascular and rheumatologic disorders. However,
      the role of these drugs in renal disorders remains controversial. In the present
      review, we examine the most recent findings involving statins and renal disease
      among different clinical scenarios, including chronic kidney disease, contrast
      induced nephropathy, renal injury after coronary artery bypass surgery, and renal
      transplant patients. 

PMID- 24729725
TI  - Use of the Tego needlefree connector is associated with reduced incidence of
      catheter-related bloodstream infections in hemodialysis patients.
AB  - BACKGROUND AND OBJECTIVES: Catheter-related bloodstream infections (CRBSIs) are
      common in hemodialysis patients using central venous catheters, and catheter
      occlusion also occurs frequently. The Tego needlefree connector was developed to
      reduce the incidence of these complications; however, existing studies of its
      effectiveness and safety are limited. MATERIALS AND METHODS: This retrospective
      analysis compared outcomes among patients of a large dialysis organization
      receiving in-center hemodialysis using a central venous catheter with either the
      Tego connector or standard catheter caps between October 1 and June 30, 2013.
      Incidence rates for intravenous (IV) antibiotic starts, receipt of an IV
      antibiotic course, positive blood cultures, mortality, and missed dialysis
      treatments were calculated, and incidence-rate ratios (IRRs) were estimated using
      Poisson regression models. Utilization of erythropoiesis-stimulating agents
      (ESAs) and thrombolytics was described for each patient-month and compared using
      mixed linear models. Models were run without adjustment, adjusted for covariates
      that were imbalanced between cohorts, or fully adjusted for all potential
      confounders. RESULTS: The analysis comprised 10,652 Tego patients and 6,493
      controls. Tego use was independently associated with decreased risk of CRBSI,
      defined by initiation of IV antibiotics (adjusted IRR 0.92, 95% confidence
      interval [CI] 0.87-0.97) or initiation of IV antibiotic course (adjusted IRR
      0.89, 95% CI 0.84-0.95). Tego use was independently associated with decreased
      rate of missed dialysis treatments (adjusted IRR 0.98, 95% CI 0.97-1.00); no
      significant difference between Tego and control cohorts was observed with respect
      to mortality. Tego use was associated with decreased likelihood of thrombolytic
      use (adjusted per-month probability of 5.6% versus 6.2% for controls) and lower
      utilization of ESAs in study months 7-9. CONCLUSION: Use of the Tego connector
      may reduce the risk of CRBSI and result in lower utilization of thrombolytics,
      antibiotics, and ESAs, as well as fewer missed dialysis treatments.

PMID- 24729726
TI  - Role of pneumococcal vaccination in prevention of pneumococcal disease among
      adults in Singapore.
AB  - The burden of disease associated with Streptococcus pneumoniae infection in
      adults can be considerable but is largely preventable through routine
      vaccination. Although substantial progress has been made with the recent
      licensure of the new vaccines for prevention of pneumonia in adults, vaccine
      uptake rates need to be improved significantly to tackle adult pneumococcal
      disease effectively. Increased education regarding pneumococcal disease and
      improved vaccine availability may contribute to a reduction in pneumococcal
      disease through increased vaccination rates. The increase in the elderly
      population in Singapore as well as globally makes intervention in reducing
      pneumococcal disease an important priority. Globally, all adult vaccines remain
      underused and family physicians give little priority to pneumococcal vaccination
      for adults in daily practice. Family physicians are specialists in preventive
      care and can be leaders in ensuring that adult patients get the full benefit of
      protection against vaccine-preventable diseases. They can play a key role in the
      immunization delivery of new and routine vaccines by educating the public on the
      risks and benefits associated with vaccines. Local recommendations by advisory
      groups on vaccination in adults will also help to tackle vaccine preventable
      diseases in adults. 

PMID- 24729727
TI  - Extensively drug-resistant tuberculosis: epidemiology and management.
AB  - The advent of antibiotics for the treatment of tuberculosis (TB) represented a
      major breakthrough in the fight against the disease. However, since its first
      use, antibiotic therapy has been associated with the emergence of resistance to
      drugs. The incorrect use of anti-TB drugs, either due to prescription errors, low
      patient compliance, or poor quality of drugs, led to the widespread emergence of
      Mycobacterium tuberculosis strains with an expanding spectrum of resistance. The
      spread of multidrug-resistant (MDR) strains (ie, strains resistant to both
      isoniazid and rifampicin) has represented a major threat to TB control since the
      1990s. In 2006, the first cases of MDR strains with further resistance to
      fluoroquinolone and injectable drugs were described and named extensively drug
      resistant TB (XDR-TB). The emergence of XDR-TB strains is a result of
      mismanagement of MDR cases, and treatment relies on drugs that are less potent
      and more toxic than those used to treat drug-susceptible or MDR strains.
      Furthermore, treatment success is lower and mortality higher than achieved in MDR
      TB cases, and the number of drugs necessary in the intensive phase of treatment
      may be higher than the four drugs recommended for MDR-TB. Linezolid may represent
      a valuable drug to treat cases of XDR-TB. Delamanid, bedaquiline, and PA-824 are
      new anti-TB agents in the development pipeline that have the potential to enhance
      the cure rate of XDR-TB. The best measures to prevent new cases of XDR-TB are the
      correct management of MDR-TB patients, early detection, and proper treatment of
      existing patients with XDR-TB. 

PMID- 24729728
TI  - Epidemiology of yaws: an update.
AB  - Yaws, a neglected tropical disease, is targeted for eradication by 2020 through
      large-scale mass-treatment programs of endemic communities. A key determinant for
      the success of the eradication campaign is good understanding of the disease
      epidemiology. We did a review of historical trends and new information from
      endemic countries, with the aim of assessing the state of knowledge on yaws
      disease burden. Transmission of yaws is now present in Africa, Asia, and the
      South Pacific. At least 12 countries are known to harbor yaws cases and 21 to 42
      million people live in endemic areas. Between 2008 and 2012 more than 300,000 new
      cases were reported to the World Health Organization. Yaws presented high
      geographical variation within a country or region, high seasonality for incidence
      of active disease, and evidence that low standards of hygiene predispose to
      suffering of the disease. Key data issues include low levels of reporting,
      potential misdiagnosis, and scarce documentation on prevalence of asymptomatic
      infections. Currently available data most likely underestimates the magnitude of
      the disease burden. More effort is needed in order to refine accuracy of data
      currently being reported. A better characterization of the epidemiology of yaws
      globally is likely to positively impact on planning and implementation of yaws
      eradication. 

PMID- 24729729
TI  - Clinical utility of dental cone-beam computed tomography: current perspectives.
AB  - Panoramic radiography and computed tomography were the pillars of maxillofacial
      diagnosis. With the advent of cone-beam computed tomography, dental practice has
      seen a paradigm shift. This review article highlights the potential applications
      of cone-beam computed tomography in the fields of dental implantology and
      forensic dentistry, and its limitations in maxillofacial diagnosis. 

PMID- 24729730
TI  - Efficacy, safety, and applicability of outpatient treatment for diverticulitis.
AB  - Acute diverticulitis of the colon represents a significant burden for national
      health systems, in terms of direct and indirect costs. Although current
      guidelines recommend use of antibiotics for the outpatient treatment of acute
      uncomplicated diverticulitis, evidence for this is still lacking. Hence,
      significant effort is now being made to identify the appropriate therapeutic
      approach to treat and prevent relapses of diverticulitis. Outpatient treatment
      has been identified as a safe and effective therapeutic approach in up to 90% of
      patients with uncomplicated diverticulitis. It allows important costs saving to
      health systems without a negative influence on quality of life for patients with
      uncomplicated diverticulitis, and reduces health care costs by more than 60%. 

PMID- 24729731
TI  - Benefit-risk assessment of new and emerging treatments for hepatitis C: focus on
      simeprevir and sofosbuvir.
AB  - Greater understanding of the hepatitis C virus (HCV) genome and life cycle of the
      HCV virion allows for new targets for therapy that directly act on the viral
      machinery to inhibit replication. Numerous direct-acting antivirals are in
      development, and four have been brought to market. Simeprevir, a second
      generation protease inhibitor, has been approved for HCV genotype 1 patients in
      combination with pegylated interferon-alpha and ribavirin. Sofosbuvir, a novel
      nucleotide analog, has pangenotypic coverage and has been approved for HCV
      genotype 1 patients with ribavirin and pegylated interferon-alpha. For HCV
      genotypes 2 and 3, an all-oral regimen of sofosbuvir with ribavirin has become
      the new gold standard for treatment. The efficacy and safety for these two novel
      therapies among various subpopulations of those infected with chronic hepatitis C
      are discussed in the following review. In addition, off-label and future
      therapeutic regimens are addressed, as well as the concerns about cost of current
      and future therapies. 

PMID- 24729732
TI  - Profile of vintafolide (EC145) and its use in the treatment of platinum-resistant
      ovarian cancer.
AB  - OBJECTIVE: Our aim was to review the profile of vintafolide (EC145) and its
      rationale for use in platinum-resistant ovarian cancer. First we investigated the
      folate receptors (FRs), folate's pathway into cells, and its expression in normal
      and cancerous cells, before detailing the mechanism of action of vintafolide, its
      clinical applications, and the results of different study phases. MATERIALS AND
      METHODS: A literature search was conducted through PubMed/Medline, Google,
      ClinicalTrials.gov and websites of pharmaceutical companies. Only articles in
      English were selected. All articles investigating folate receptor expression in
      ovarian cancer were selected first, than articles reviewing platinum resistance.
      Papers about vintafolide were collected, while those talking about synthesis and
      biochemistry concerns were excluded. The different Phase I and II studies were
      read, and an update on the website of pharmaceuticals companies were added.
      RESULTS: FR is a bundle-membrane receptor that is expressed normally in some
      normal tissues on the apical surface of cells, but highly expressed in ovarian
      cancer cells (>80%). It collects folate through endocytosis. Chemotherapy does
      not modify its expression in ovarian cancer cells, and its expression appears to
      be mostly associated with a poor prognosis and platinum resistance. Vintafolide
      is a folate-desacetylvinblastine monohydrazide conjugate, allowing a liberation
      of the drug into the cytoplasm of cancerous cells via the FR-alpha (FRalpha) and
      endocytosis, with high specificity. Phase I studies showed a 2.5 mg bolus dose to
      be nontoxic, with moderately adverse events. Phase II clinical trials for the
      first time demonstrated a statistically significant improvement in disease-free
      survival in patients with platinum-resistant ovarian cancer, and in those with a
      very poor prognosis who had already received three to four lines of systemic
      chemotherapy. The greater benefits were observed in patients with highly
      expressed FRalpha. CONCLUSION: Vintafolide is a promising targeted agent for
      recurrent platinum-resistant ovarian cancer, first, thanks to its mechanism of
      action and the characteristics of FRalpha in ovarian cancer, and, second, because
      of the favorable results observed in the first clinical trials on platinum
      resistant ovarian cancer. Phase III clinical trials are currently ongoing and are
      expected to confirm these results.

PMID- 24729733
TI  - Tertiary care availability and adolescent pregnancy characteristics in Saudi
      Arabia.
AB  - BACKGROUND: In this study, we aimed to assess the rate of adolescent delivery in
      a Saudi tertiary health care center and to investigate the association between
      maternal age and fetal, neonatal, and maternal complications where a professional
      tertiary medical care service is provided. METHODS: A cross-sectional study was
      performed between 2005 and 2010 at King Abdulaziz Medical City, Riyadh, Saudi
      Arabia. All primigravid Saudi women >=24 weeks gestation, carrying a singleton
      pregnancy, aged <35 years, and with no chronic medical problems were eligible.
      Women were divided into three groups based on their age, ie, group 1 (G1) <16
      years, group 2 (G2) >=16 up to 19 years, and group 3 (G3) >=19 up to 35 years.
      Data were collected from maternal and neonatal medical records. We calculated the
      association between the different age groups and maternal characteristics, as
      well as events and complications during the antenatal period, labor, and
      delivery. RESULTS: The rates of adolescent delivery were 20.0 and 16.3 per 1,000
      births in 2009 and 2010, respectively. Compared with G1 and G2 women, G3 women
      tended to have a higher body mass index, a longer first and second stage of
      labor, more blood loss at delivery, and a longer hospital stay. Compared with G1
      and G2 women, respectively, G3 women had a 42% and a 67% increased risk of
      cesarean section, and had a 52% increased risk of instrumental delivery. G3 women
      were more likely to develop gestational diabetes or anemia, G2 women had a three
      fold increased risk of premature delivery (odds ratio 2.81), and G3 neonates had
      a 50% increased overall risk of neonatal complications (odds ratio 0.51).
      CONCLUSION: The adolescent birth rate appears to be low in central Saudi Arabia
      compared with other parts of the world. Excluding preterm delivery, adolescent
      delivery cared for in a tertiary health care center is not associated with a
      significantly increased medical risk to the mother, fetus, or neonate. The
      psychosocial effect of adolescent pregnancy and delivery needs to be assessed.

PMID- 24729734
TI  - International survey to assess women's attitudes regarding choice of daily versus
      nondaily female hormonal contraception.
AB  - BACKGROUND: The availability of reliable contraception tailored to suit women's
      needs and lifestyles is an essential step in addressing unintended pregnancy and
      its substantial human and financial costs. The daily combined oral contraceptive
      pill has been the short-acting hormonal contraceptive of choice for the last 50
      years. However, for some women, this may be neither suitable nor optimal.
      METHODS: Here we report the findings of a large, online, questionnaire-based
      study conducted in Brazil, France, Germany, Italy, and the USA. The study was
      designed to assess women's attitudes, beliefs, and unmet needs regarding current
      hormonal contraceptive options via an anonymous online survey. Women eligible for
      contraception were required to respond to questions using either a binary
      (yes/no) or seven-point scale (1, complete disagreement; 7, complete agreement).
      Women were also asked about other relevant issues, such as lifestyle, perception
      of menstruation and pregnancy, level of education, and relationship with their
      health care professional. RESULTS: In total, 12,094 women were questioned, of
      whom 68% required contraception. Overall, 28% of women expressed an interest in
      novel contraceptive products, and 49% stated that they would prefer a nondaily
      method. Although many women expressed satisfaction with the pill, daily intake
      was thought to be burdensome, resulting in irregular and ineffective usage.
      However, many women continued to choose the pill due to lack of consideration of
      and education about other options. Approximately half of the women wished to
      conceive in the near future. CONCLUSION: The findings indicate that nearly half
      of respondents would prefer a nondaily form of contraception. Furthermore,
      approximately half of respondents wished to conceive in the near future,
      suggesting that they are unlikely to favor long-acting options. Effective
      education on contraceptive choices may help women to find the method that best
      suits their needs, thus improving contraceptive compliance.

PMID- 24729735
TI  - Overflow proteinuria as a manifestation of unrecognized polymyositis.
AB  - Polymyositis is a rare and gradually progressive autoimmune disease of skeletal
      muscle. Two main types of renal involvement have been described: acute tubular
      necrosis related to rhabdomyolysis and glomerulonephritis. However, cases of
      overflow proteinuria related to polymyositis have rarely been reported. Herein,
      we report a case of a 41-year-old male who presented with edema of both lower
      extremities. Laboratory studies revealed elevated creatine phosphokinase level,
      hypoalbuminemia, and a moderate amount of proteinuria, although albuminuria was
      not dominant. Urine electrophoresis showed an abnormally restricted zone in the
      beta-fraction, which suggested overflow proteinuria of non-glomerular origin.
      Despite intravenous hydration, his serum creatine phosphokinase level did not
      decrease and his symptoms did not improve. Electromyography showed myopathy, and
      muscle biopsy revealed findings consistent with polymyositis. After
      corticosteroid therapy, his creatine phosphokinase level and proteinuria
      decreased and his clinical symptoms improved. This case demonstrates an atypical
      presentation of polymyositis manifested by overflow proteinuria. 

PMID- 24729737
TI  - Effect of mass media and Internet on sexual behavior of undergraduates in Osogbo
      metropolis, Southwestern Nigeria.
AB  - INTRODUCTION: The influence of media portrayals of sexual attitudes and normative
      expectations of young people at a critical developmental stage is of public
      health concern. OBJECTIVES: To examine the role of mass media and Internet
      utilization in shaping the sexual health attitudes and behaviors of young
      undergraduates in Osogbo metropolis, Osun State, Nigeria. MATERIALS AND METHODS:
      In a descriptive cross-sectional study, 400 undergraduates were selected using a
      multistage random sampling technique. Four hundred and fifty pretested,
      semistructured questionnaires were distributed; of these, 400 were returned
      properly filled. Data were analyzed using SPSS statistical software version 16.
      RESULTS: Mean age of respondents +/- standard deviation was 23.6+/-2.99 years.
      Most were aware of the various forms of mass media (>95%). Most (64.0%)
      respondents spent 1-5 hours watching television, daily, and most used the
      Internet often. About 38.3% and 24.2% of respondents used the Internet and
      radio/television, respectively, as sources of information on sexual issues. Most
      respondents used the Internet for school assignments (83.0%, n=332), electronic
      mail (89.0%, n=356), and for accessing sexually explicit materials (74.5%,
      n=298). Most of the respondents (73.5%) opined that the Internet has a bad
      influence on youths' sexual behavior, although accessing the Internet for sexual
      material or movies was acceptable to 25.3% of them. Of the 226 respondents who
      had ever had sex, 226 (100%), 37 (16.4%), 31 (13.7%), and 10 (4.4%) practiced
      coitus, oral sex, masturbation, and anal sex, respectively; 122 (54.0%) always
      used condoms, whereas 90 (40.0%) never used condoms during sexual activity; 33
      (14.6%) had had sex with commercial sex workers. Further analysis showed that
      those who were yet to marry (single) were less likely to be sexually experienced
      than those who were married (adjusted odds ratio [AOR] =0.075, 95% confidence
      interval [CI] =0.008-0.679), and those who said accessing the Internet for sexual
      material is not acceptable to them were also less likely to be sexually
      experienced than those to whom it was acceptable (AOR =0.043, 95% CI =0.016
      0.122). Predictors of having multiple sexual partners include the sex of the
      respondent and the frequency of Internet use, with females (AOR =0.308, 95% CI
      =0.113-0.843) and those who rarely use the Internet less likely to have multiple
      sexual partners. CONCLUSION: We conclude that uncontrolled exposure to mass media
      and Internet could negatively influence the sexual patterns and behavior of
      youths.

PMID- 24729736
TI  - Managing inflammatory bowel disease in adolescent patients.
AB  - Increasing numbers of adolescents are being diagnosed with Crohn's disease or
      ulcerative colitis, the two main subtypes of inflammatory bowel disease. These
      young people face many short- and long-term challenges; one or more medical
      therapies may be required indefinitely; their disease may have great impact, in
      terms of their schooling and social activities. However, the management of
      adolescents with one of these incurable conditions needs to encompass more than
      just medical therapies. Growth, pubertal development, schooling, transition,
      adherence, and psychological well-being are all important aspects. A
      multidisciplinary team setting, catering to these components of care, is required
      to ensure optimal outcomes in adolescents with inflammatory bowel disease. 

PMID- 24729738
TI  - Management of psoriasis in adolescence.
AB  - Psoriasis is a chronic inflammatory cutaneous disorder affecting 2%-4% of the
      world's population. The prevalence of the disease in childhood and adolescence
      ranges between 0.5% and 2%. The management of psoriasis in adolescence is an
      intriguing and complicated task. Given the paucity of officially approved
      therapies, the very limited evidence-based data from randomized controlled
      trials, and the absence of standardized guidelines, physicians must rely on
      published experience from case reports both from the field of dermatology as well
      as from the application of these drugs for other pediatric conditions coming from
      the disciplines of rheumatology, gastroenterology, and oncology. Psoriatic
      adolescents deal with a potentially disfiguring and lifelong disease that could
      permanently impair their psychological development. It must be clarified to them
      that psoriasis does not have a permanent cure, and therefore the main goal of
      treatments is to establish disease control and prolonged periods between flares.
      The majority of adolescents suffer from mild psoriasis, and thus they are treated
      basically with topical treatment modalities. Phototherapy is reserved for
      adolescents with mild-to-moderate plaque disease and/or guttate psoriasis when
      routine visits to specialized centers do not create practical problems. Systemic
      agents and biologics are administered to patients with moderate-to-severe plaque
      psoriasis, pustular psoriasis, or erythrodermic psoriasis. 

PMID- 24729739
TI  - Clinical utility of etanercept in the treatment of arthritides in children and
      adolescents.
AB  - Juvenile idiopathic arthritis (JIA) is a group of chronic inflammatory diseases
      affecting approximately 300,000 children and adolescents in the United States of
      unknown cause. It can affect children from the age of 0 years up to the age of 16
      years. The International League of Associations of Rheumatology has defined seven
      subsets of JIA based on several factors including the number of affected joints
      and the involvement of other tissues; the prognosis for each affected child also
      depends on multiple factors including age of onset, number of joints involved,
      and systemic features. As with rheumatoid arthritis in adults, the goal of
      therapy is remission and resolution of disease activity; however, as a cure does
      not seem attainable in the near future, a reasonable goal of therapy is
      prevention of joint damage, inhibition of inflammation, and a high level of
      quality of life. Even with available therapies, many children with JIA enter
      adulthood with persistently active disease, suboptimal function, and impaired
      quality of life. Methotrexate remains the standard of care for children with JIA;
      etanercept was approved in 2000 in the United States for the treatment of JIA
      resistant to methotrexate. The efficacy and safety of etanercept therapy in
      children with JIA is reviewed and its place in the therapeutic regimen is
      discussed; the available long term data is also presented. The data presented was
      obtained from a PubMed search as well as a review of the references presented in
      the 2011 American College of Rheumatology Recommendations for the Treatment of
      Juvenile Idiopathic Arthritis and the 2013 Update. It is hoped that treatment
      with etanercept and other biologic therapies will lead to improved outcomes for
      children with JIA in the future. 

PMID- 24729740
TI  - Measurement Error in Spatial Exposure Models: Study Design Implications.

PMID- 24729741
TI  - Determination of Absolute Configuration of Natural Products: Theoretical
      Calculation of Electronic Circular Dichroism as a Tool.
AB  - Determination of absolute configuration (AC) is one of the most challenging
      features in the structure elucidation of chiral natural products, especially
      those with complex structures. With revolutionary advancements in the area of
      quantum chemical calculations of chiroptical spectroscopy over the past decade,
      the time dependent density functional theory (TDDFT) calculation of electronic
      circular dichroism (ECD) spectra has emerged as a very promising tool. The
      principle is simply based on the comparison of the calculated and experimental
      ECD spectra: the more closely they match, the more reliable conclusion for the AC
      assignment can be drawn. This review attempts to use several examples
      representing monomeric flavonoids, rotationally restricted biflavonoids, complex
      hexahydroxydiphenoyl-containing flavonoids, conformationally flexible and
      restrained sesquiterpenoids, cembrane-africanene terpenoids,
      dihydropyranocoumarins, alkaloids, and dihydroxanthones to illustrate the
      applicability of this approach in determining the AC of structurally diverse
      natural products. The findings clearly indicate that the TDDFT calculation of ECD
      spectra can quantify the contribution of individual conformers and the
      interaction of multiple chromophores, making it possible to determine the AC of
      complex chiral molecules. The calculated electronic transitions and molecular
      orbitals provide new insight into the interpretation of ECD spectra at the
      molecular level.

PMID- 24729743
TI  - Heterogeneity in Maltreated and Non-maltreated Preschool Children's Inhibitory
      Control: The Interplay Between Parenting Quality and Child Temperament.
AB  - This study examined the contribution of child temperament, parenting, and their
      interaction on inhibitory control development in a sample of maltreated and non
      maltreated preschool children. One hundred and eighteen mother-child dyads were
      drawn from predominantly low-income, rural communities. Dyads participated in a
      laboratory session in which maternal warm autonomy support, warm guidance, and
      strict/hostile control were observationally coded during a joint teaching task.
      Independent assessments of children's inhibitory control were obtained, and
      observers rated children's temperament. After relevant covariates, including
      income, maternal education, and child age and IQ were controlled for, there were
      no differences between the maltreatment and non-maltreatment groups in either
      children's inhibitory control or mothers' behaviours in the laboratory session.
      Even after much of the variance in children's inhibitory control was accounted
      for from the covariates, children's temperamental negativity moderated the
      effects of warm autonomy support on inhibitory control in both maltreatment and
      non-maltreatment groups. Temperamentally negative children whose mothers
      displayed more warm autonomy support showed greater inhibitory control, at levels
      on par with low-negative children. Findings suggest that heterogeneity in
      children's self-regulation may be due in part to individual differences in
      sensitivity to caregiver support for children's independence, even among those
      exposed to maltreatment.

PMID- 24729742
TI  - Towards a computational model of a methane producing archaeum.
AB  - Progress towards a complete model of the methanogenic archaeum Methanosarcina
      acetivorans is reported. We characterized size distribution of the cells using
      differential interference contrast microscopy, finding them to be ellipsoidal
      with mean length and width of 2.9  MU m and 2.3  MU m, respectively, when grown
      on methanol and 30% smaller when grown on acetate. We used the single molecule
      pull down (SiMPull) technique to measure average copy number of the Mcr complex
      and ribosomes. A kinetic model for the methanogenesis pathways based on
      biochemical studies and recent metabolic reconstructions for several related
      methanogens is presented. In this model, 26 reactions in the methanogenesis
      pathways are coupled to a cell mass production reaction that updates enzyme
      concentrations. RNA expression data (RNA-seq) measured for cell cultures grown on
      acetate and methanol is used to estimate relative protein production per mole of
      ATP consumed. The model captures the experimentally observed methane production
      rates for cells growing on methanol and is most sensitive to the number of methyl
      coenzyme-M reductase (Mcr) and methyl-tetrahydromethanopterin:coenzyme-M
      methyltransferase (Mtr) proteins. A draft transcriptional regulation network
      based on known interactions is proposed which we intend to integrate with the
      kinetic model to allow dynamic regulation. 

PMID- 24729744
TI  - Psychographic Segments of College Females and Males in Relation to Substance Use
      Behaviors.
AB  - OBJECTIVES: A common commercial marketing segmentation technique is to divide a
      population into groups based on psychographic characteristics (i.e., attitudes
      and interests). We used this approach to define segments of female and male
      college students and examine substance use differences. METHOD: We administered
      an online survey to 24,055 students at six colleges in the Southeastern United
      States (response rate 20.1%, n = 4,840), obtaining complete data from 3,469
      participants. We assessed sociodemographics, psychographic factors such as those
      used by the tobacco industry to define market segments, and substance use
      (cigarettes, other tobacco products, alcohol, and marijuana). Cluster analysis
      was conducted among females and males using 15 psychographic measures (sensation
      seeking, Big Five personality traits, and nine measures adapted from tobacco
      industry documents), identifying three segments per sex. RESULTS: Safe
      responsibles were characterized by high levels of agreeableness,
      conscientiousness, emotional stability, academic achievement, and religious
      service attendance. Stoic individualists were characterized by low extraversion,
      sensation seeking, and openness. Thrill-seeking socializers were characterized by
      high levels of sensation seeking and extraversion. Among females, thrill-seeking
      socializers were significantly more likely than safe responsibles to have used
      any substance in the prior 30 days (odds ratio [OR] = 2.04, 95% confidence
      interval [CI] [1.65, 2.52]; Nagelkerke R2 = .084). Among males, stoic
      individualists (OR = 1.50, CI [1.08, 2.08]) and thrill-seeking socializers (OR =
      1.53, CI [1.09, 2.13]) were more likely than safe responsibles to have used
      substances in the past 30 days (Nagelkerke R2: .109). CONCLUSION: Psychographic
      segmentation can identify young adult subgroups with differing psychographic and
      substance use profiles and inform health campaigns and messaging targeting youth.

PMID- 24729745
TI  - Clinical Care at the Genomic Interface: Current Genetic Issues in Neonatal
      Nursing.
AB  - Although only one in 33 infants is born with a genetic condition, neonatal nurses
      have a growing responsibility to integrate genetic competency into their clinical
      practice. This review article outlines the specific aspects of assessment,
      genetic screening and testing, and communication of genetic information between
      provider and patient in both the newborn and pregnancy period. Essential nursing
      competencies are introduced as a framework for building a skill and knowledge set
      in clinical genetics as it applies to neonatal care. The potential development of
      inquiry and research oriented practice problems are also highlighted. The
      exponential growth of human genetic and genomic information drives the need for
      neonatal nursing to embrace the interface of clinical care and genetic issues.

PMID- 24729746
TI  - Accelerating Virtual High-Throughput Ligand Docking: current technology and case
      study on a petascale supercomputer.
AB  - In this paper we give the current state of high-throughput virtual screening. We
      describe a case study of using a task-parallel MPI (Message Passing Interface)
      version of Autodock4 [1], [2] to run a virtual high-throughput screen of one
      million compounds on the Jaguar Cray XK6 Supercomputer at Oak Ridge National
      Laboratory. We include a description of scripts developed to increase the
      efficiency of the predocking file preparation and postdocking analysis. A
      detailed tutorial, scripts, and source code for this MPI version of Autodock4 are
      available online at http://www.bio.utk.edu/baudrylab/autodockmpi.htm.

PMID- 24729747
TI  - Extending SemRep to the Public Health Domain.
AB  - We describe the use of a domain-independent methodology to extend a natural
      language processing (NLP) application, SemRep (Rindflesch, Fiszman, & Libbus,
      2005), based on the knowledge sources afforded by the Unified Medical Language
      System (UMLS(r)) (Humphreys, Lindberg, Schoolman, & Barnett, 1998) to support the
      area of health promotion within the public health domain. Public health
      professionals require good information about successful health promotion policies
      and programs that might be considered for application within their own
      communities. Our effort seeks to improve access to relevant information for the
      public health profession, to help those in the field remain an information-savvy
      workforce. NLP and semantic techniques hold promise to help public health
      professionals navigate the growing ocean of information by organizing and
      structuring this knowledge into a focused public health framework paired with a
      user-friendly visualization application as a way to summarize results of PubMed
      searches in this field of knowledge.

PMID- 24729748
TI  - Music emotion detection using hierarchical sparse kernel machines.
AB  - For music emotion detection, this paper presents a music emotion verification
      system based on hierarchical sparse kernel machines. With the proposed system, we
      intend to verify if a music clip possesses happiness emotion or not. There are
      two levels in the hierarchical sparse kernel machines. In the first level, a set
      of acoustical features are extracted, and principle component analysis (PCA) is
      implemented to reduce the dimension. The acoustical features are utilized to
      generate the first-level decision vector, which is a vector with each element
      being a significant value of an emotion. The significant values of eight main
      emotional classes are utilized in this paper. To calculate the significant value
      of an emotion, we construct its 2-class SVM with calm emotion as the global (non
      target) side of the SVM. The probability distributions of the adopted acoustical
      features are calculated and the probability product kernel is applied in the
      first-level SVMs to obtain first-level decision vector feature. In the second
      level of the hierarchical system, we merely construct a 2-class relevance vector
      machine (RVM) with happiness as the target side and other emotions as the
      background side of the RVM. The first-level decision vector is used as the
      feature with conventional radial basis function kernel. The happiness
      verification threshold is built on the probability value. In the experimental
      results, the detection error tradeoff (DET) curve shows that the proposed system
      has a good performance on verifying if a music clip reveals happiness emotion. 

PMID- 24729749
TI  - Evaluation of senior dental students' general attitude towards the use of rubber
      dam: a survey among two dental schools.
AB  - The purpose of this study was to evaluate the general attitude of senior dental
      students towards rubber dam use, specifically focusing on endodontic practices
      prior to starting to serve community. Questionnaires were distributed to senior
      year students of a private school and a state school in Istanbul. Questions were
      asked about areas where the students used rubber dam, its advantages and
      difficulties, and whether they agreed or disagreed with some aspects of the
      rubber dam. The private school students rated isolation whereas those of the
      state school selected prevention of aspiration which the top advantage rubber dam
      provides. Students of the state school agreed with the opinion that isolation
      cannot be achieved without rubber dam and it extended the procedure with a
      significantly higher ratio compared to the private school. Within the limitations
      of the present study, it can be concluded that the perceptions of dental students
      on rubber dam needs to be improved and strategies should be developed so that
      this valuable adjunct will comprise one of the indispensable elements of dental
      care.

PMID- 24729750
TI  - A master-slave surveillance system to acquire panoramic and multiscale videos.
AB  - This paper describes a master-slave visual surveillance system that uses
      stationary-dynamic camera assemblies to achieve wide field of view and selective
      focus of interest. In this system, the fish-eye panoramic camera is capable of
      monitoring a large area, and the PTZ dome camera has high mobility and zoom
      ability. In order to achieve the precise interaction, preprocessing spatial
      calibration between these two cameras is required. This paper introduces a novel
      calibration approach to automatically calculate a transformation matrix model
      between two coordinate systems by matching feature points. In addition, a
      distortion correction method based on Midpoint Circle Algorithm is proposed to
      handle obvious horizontal distortion in the captured panoramic image.
      Experimental results using realistic scenes have demonstrated the efficiency and
      applicability of the system with real-time surveillance. 

PMID- 24729751
TI  - Reusable component model development approach for parallel and distributed
      simulation.
AB  - Model reuse is a key issue to be resolved in parallel and distributed simulation
      at present. However, component models built by different domain experts usually
      have diversiform interfaces, couple tightly, and bind with simulation platforms
      closely. As a result, they are difficult to be reused across different simulation
      platforms and applications. To address the problem, this paper first proposed a
      reusable component model framework. Based on this framework, then our reusable
      model development approach is elaborated, which contains two phases: (1) domain
      experts create simulation computational modules observing three principles to
      achieve their independence; (2) model developer encapsulates these simulation
      computational modules with six standard service interfaces to improve their
      reusability. The case study of a radar model indicates that the model developed
      using our approach has good reusability and it is easy to be used in different
      simulation platforms and applications. 

PMID- 24729752
TI  - The effect of obesity on brain diffusion alteration in patients with obstructive
      sleep apnea.
AB  - PURPOSE: We investigated diffusion alterations in specific regions of the brain
      in morbid obese, obese, and nonobese OSA patients and searched whether there is a
      correlation between BMI and ADC values. MATERIALS AND METHODS: DWIs of 65
      patients with OSA were evaluated. The patients were classified according to BMI
      as morbid obese (n = 16), obese (n = 27), and nonobese (control, n = 22) groups.
      ADC measurements were performed from 24 different regions of the brain in each
      patient. The relationship of BMI with ADC values was searched. RESULTS: The ADC
      values in hypothalamus, insular cortex, parietal cortex, caudate nucleus, frontal
      white matter, and posterior limb of internal capsule were all increased in obese
      patients (n = 43) compared to control group. The ADC values of midbrain,
      hypothalamus, orbitofrontal cortex, and parietal cortex were significantly
      increased in morbid obese compared to obese patients. In obese patients, the
      degree of BMI was positively correlated with ADC values of orbitofrontal cortex,
      parietal cortex, and hypothalamus. CONCLUSION: We observed increasing brain
      vasogenic edema with increasing BMI, suggesting that the main reason of brain
      diffusion alteration in patients with OSA could be obesity related.

PMID- 24729753
TI  - On a new efficient Steffensen-like iterative class by applying a suitable self
      accelerator parameter.
AB  - It is attempted to present an efficient and free derivative class of Steffensen
      like methods for solving nonlinear equations. To this end, firstly, we construct
      an optimal eighth-order three-step uniparameter without memory of iterative
      methods. Then the self-accelerator parameter is estimated using Newton's
      interpolation in such a way that it improves its convergence order from 8 to 12
      without any extra function evaluation. Therefore, its efficiency index is
      increased from 8(1/4) to 12(1/4) which is the main feature of this class. To show
      applicability of the proposed methods, some numerical illustrations are
      presented. 

PMID- 24729755
TI  - A GA-based approach to hide sensitive high utility itemsets.
AB  - A GA-based privacy preserving utility mining method is proposed to find
      appropriate transactions to be inserted into the database for hiding sensitive
      high utility itemsets. It maintains the low information loss while providing
      information to the data demanders and protects the high-risk information in the
      database. A flexible evaluation function with three factors is designed in the
      proposed approach to evaluate whether the processed transactions are required to
      be inserted. Three different weights are, respectively, assigned to the three
      factors according to users. Moreover, the downward closure property and the
      prelarge concept are adopted in the proposed approach to reduce the cost of
      rescanning database, thus speeding up the evaluation process of chromosomes. 

PMID- 24729756
TI  - Gating techniques for Rao-Blackwellized Monte Carlo data association filter.
AB  - This paper studies the Rao-Blackwellized Monte Carlo data association (RBMCDA)
      filter for multiple target tracking. The elliptical gating strategies are
      redesigned and incorporated into the framework of the RBMCDA filter. The obvious
      benefit is the reduction of the time cost because the data association procedure
      can be carried out with less validated measurements. In addition, the overlapped
      parts of the neighboring validation regions are divided into several separated
      subregions according to the possible origins of the validated measurements. In
      these subregions, the measurement uncertainties can be taken into account more
      reasonably than those of the simple elliptical gate. This would help to achieve
      higher tracking ability of the RBMCDA algorithm by a better association prior
      approximation. Simulation results are provided to show the effectiveness of the
      proposed gating techniques. 

PMID- 24729754
TI  - Overview of platelet physiology: its hemostatic and nonhemostatic role in disease
      pathogenesis.
AB  - Platelets are small anucleate cell fragments that circulate in blood playing
      crucial role in managing vascular integrity and regulating hemostasis. Platelets
      are also involved in the fundamental biological process of chronic inflammation
      associated with disease pathology. Platelet indices like mean platelets volume
      (MPV), platelets distributed width (PDW), and platelet crit (PCT) are useful as
      cheap noninvasive biomarkers for assessing the diseased states. Dynamic platelets
      bear distinct morphology, where alpha and dense granule are actively involved in
      secretion of molecules like GPIIb , IIIa, fibrinogen, vWf, catecholamines,
      serotonin, calcium, ATP, ADP, and so forth, which are involved in aggregation.
      Differential expressions of surface receptors like CD36, CD41, CD61 and so forth
      have also been quantitated in several diseases. Platelet clinical research faces
      challenges due to the vulnerable nature of platelet structure functions and lack
      of accurate assay techniques. But recent advancement in flow cytometry inputs
      huge progress in the field of platelets study. Platelets activation and
      dysfunction have been implicated in diabetes, renal diseases, tumorigenesis,
      Alzheimer's, and CVD. In conclusion, this paper elucidates that platelets are not
      that innocent as they keep showing and thus numerous novel platelet biomarkers
      are upcoming very soon in the field of clinical research which can be important
      for predicting and diagnosing disease state. 

PMID- 24729757
TI  - The effect of prophylactic polishing pastes on surface roughness of indirect
      restorative materials.
AB  - The purpose of this study was to evaluate the influence of prophylactic polishing
      pastes (PPP; Detartrine (DT), Topex (TP)) on surface roughness (R(a)) of indirect
      composites (IRC; Tescera (TES), Gradia (GRD), and Estenia C&B (EST)), a glass
      ceramic (Empress 2 layering (E2)), and a leucite reinforced glass ceramic
      (Empress Esthetic (EE)) with two different (glazed (G); polished (P)) surface
      preparations. A total of 90 IRC and 120 ceramic discs, 8 mm in diameter and 2 mm
      thick, were prepared. E2 and EE specimens were randomly divided into two groups
      (n = 30). One group was glazed (GE2; GEE), while the other group was polished
      (PE2; PEE) the same as the IRCs. The specimens in each group were subsequently
      divided into three subgroups: control (C), DT, and TP. R(a)  (MUm) was evaluated
      with a profilometer. Data were analyzed by Kruskal Wallis, followed by the Dunn's
      multiple comparison tests (P < 0.05). DT and TP resulted in significant surface
      roughening for TES, GRD, and EST, while no significant differences were detected
      between DT and TP (P > 0.05). PE2 and PEE were not affected by DT or TP (P >
      0.05), while GE2 and GEE exhibited significant roughening after TP (P < 0.05).
      Surface roughness of IRCs and glazed ceramics can be affected by PPP
      applications.

PMID- 24729758
TI  - Depression in Late-Life: a Focus on Prevention.
AB  - Depression is a leading cause of disease burden, disability and distress for
      millions of older adults. Thus, prevention of late-life depression is a priority
      research area. This article addresses the science of late-life depression
      prevention with the following: 1) an introduction to the Institute of Medicine
      framework of universal, selective and indicated prevention as it pertains to late
      life depression, with particular attention to successes of indicated and
      selective prevention in primary care; 2) a discussion of how biomarkers can be
      integrated into prevention research, using interferon-alpha-induced depression as
      a model; 3) an outline for expansion of prevention to non-specialist care
      delivery systems in Low and Middle Income Countries - thus, extending the reach
      of current successful approaches; 4) a description of a novel approach to
      simultaneous testing of universal, selective and indicated prevention in late
      life depression, with emphasis on study design features required to achieve
      practical, scalable tests of health impact.

PMID- 24729759
TI  - Characterizing Data Discovery and End-User Computing Needs in Clinical
      Translational Science.
AB  - In this paper, the authors present the results of a qualitative case-study
      seeking to characterize data discovery needs and barriers of principal
      investigators and research support staff in clinical translational science.
      Several implications for designing and implementing translational research
      systems have emerged through the authors' analysis. The results also illustrate
      the benefits of forming early partnerships with scientists to better understand
      their workflow processes and end-user computing practices in accessing data for
      research. The authors use this user-centered, iterative development approach to
      guide the implementation and extension of i2b2, a system they have adapted to
      support cross-institutional aggregate anonymized clinical data querying. With
      ongoing evaluation, the goal is to maximize the utility and extension of this
      system and develop an interface that appropriately fits the swiftly evolving
      needs of clinical translational scientists.

PMID- 24729760
TI  - SPEECH SEGMENTATION IN A SIMULATED BILINGUAL ENVIRONMENT: A CHALLENGE FOR
      STATISTICAL LEARNING?
AB  - Studies using artificial language streams indicate that infants and adults can
      use statistics to correctly segment words. However, most studies have utilized
      only a single input language. Given the prevalence of bilingualism, how is
      multiple language input segmented? One particular problem may occur if learners
      combine input across languages: the statistics of particular units that overlap
      different languages may subsequently change and disrupt correct segmentation. Our
      study addresses this issue by employing artificial language streams to simulate
      the earliest stages of segmentation in adult L2-learners. In four experiments,
      participants tracked multiple sets of statistics for two artificial languages.
      Our results demonstrate that adult learners can track two sets of statistics
      simultaneously, suggesting that they form multiple representations when
      confronted with bilingual input. This work, along with planned infant
      experiments, informs a central issue in bilingualism research, namely,
      determining at what point listeners can form multiple representations when
      exposed to multiple languages.

PMID- 24729761
TI  - Extension of UNRES force field to treat polypeptide chains with D-amino-acid
      residues.
AB  - Coarse-grained force fields for protein simulations are usually designed and
      parameterized to treat proteins composed of natural L-amino-acid residues.
      However, D-amino-acid residues occur in bacterial, fungal (e.g., gramicidins), as
      well as human-designed proteins. For this reason, we have extended the UNRES
      coarse-grained force field developed in our laboratory to treat systems with D
      amino-acid residues. We developed the respective virtual-bond-torsional and
      double-torsional potentials for rotation about the C alpha . . . C alpha virtual
      bond axis and two consecutive C alpha . . . C alpha virtual-bond axes,
      respectively, as functions of virtual-bond-dihedral angles gamma. In turn, these
      were calculated as potentials of mean force (PMFs) from the diabatic energy
      surfaces of terminally-blocked model compounds for glycine, alanine, and proline.
      The potential-energy surfaces were calculated by using the ab initio method of
      molecular quantum mechanics at the Moller-Plesset (MP2) level of theory and the 6
      31G(d,p) basis set, with the rotation angles of the peptide groups about
      [Formula: see text] and [Formula: see text] used as variables, and the energy was
      minimized with respect to the remaining degrees of freedom. The PMFs were
      calculated by numerical integration for all pairs and triplets with all possible
      combinations of types (glycine, alanine, and proline) and chirality (D or L);
      however, symmetry relations reduce the number of non-equivalent torsional
      potentials to 13 and the number of double-torsional potentials to 63 for a given
      C-terminal blocking group. Subsequently, one- (for torsional) and two-dimensional
      (for double-torsional potentials) Fourier series were fitted to the PMFs to
      obtain analytical expressions. It was found that the torsional potentials of the
      x-Y and X-y types, where X and Y are Ala or Pro, respectively, and a lowercase
      letter denotes D-chirality, have global minima for small absolute values of
      gamma, accounting for the double-helical structure of gramicidin A, which is a
      dimer of two chains, each possessing an alternating D-Tyr-L-Tyr sequence, and
      similar peptides. The side-chain and correlation potentials for D-amino-acid
      residues were obtained by applying the reflection about the [Formula: see text]
      plane to the respective potentials for the L-amino-acid residues.

PMID- 24729762
TI  - String method for calculation of minimum free-energy paths in Cartesian space in
      freely-tumbling systems.
AB  - The string method is a molecular-simulation technique that aims to calculate the
      minimum free-energy path of a chemical reaction or conformational transition, in
      the space of a pre-defined set of reaction coordinates that is typically highly
      dimensional. Any descriptor may be used as a reaction coordinate, but arguably
      the Cartesian coordinates of the atoms involved are the most unprejudiced and
      intuitive choice. Cartesian coordinates, however, present a non-trivial problem,
      in that they are not invariant to rigid-body molecular rotations and
      translations, which ideally ought to be unrestricted in the simulations. To
      overcome this difficulty, we reformulate the framework of the string method to
      integrate an on-the-fly structural-alignment algorithm. This approach, referred
      to as SOMA (String method with Optimal Molecular Alignment), enables the use of
      Cartesian reaction coordinates in freely tumbling molecular systems. In addition,
      this scheme permits the dissection of the free-energy change along the most
      probable path into individual atomic contributions, thus revealing the dominant
      mechanism of the simulated process. This detailed analysis also provides a
      physically-meaningful criterion to coarse-grain the representation of the path.
      To demonstrate the accuracy of the method we analyze the isomerization of the
      alanine dipeptide in vacuum and the chair-to-inverted-chair transition of beta-D
      mannose in explicit water. Notwithstanding the simplicity of these systems, the
      SOMA approach reveals novel insights into the atomic mechanism of these
      isomerizations. In both cases, we find that the dynamics and the energetics of
      these processes are controlled by interactions involving only a handful of atoms
      in each molecule. Consistent with this result, we show that a coarse-grained SOMA
      calculation defined in terms of these subsets of atoms yields nearidentical
      minimum free-energy paths and committor distributions to those obtained via a
      highly-dimensional string.

PMID- 24729763
TI  - N-acetyl aspartate levels in adolescents with bipolar and/or cannabis use
      disorders.
AB  - OBJECTIVE: Bipolar and cannabis use disorders commonly co-occur during
      adolescence, and neurochemical studies may help clarify the pathophysiology
      underlying this co-occurrence. This study compared metabolite concentrations in
      the left ventral lateral prefrontal cortex among adolescents with bipolar
      disorder (bipolar group; n = 14), adolescents with a cannabis use disorder
      (cannabis use group; n = 13), adolescents with cannabis use and bipolar disorders
      (bipolar and cannabis group; n = 25), and healthy adolescents (healthy controls;
      n = 15). We hypothesized that adolescents with bipolar disorder (with or without
      cannabis use disorder) would have decreased N-acetyl aspartate levels in the
      ventral lateral prefrontal cortex compared to the other groups and that the
      bipolar and cannabis group would have the lowest N-acetyl aspartate levels of all
      groups. METHODS: N-acetyl aspartate concentrations in the left ventral lateral
      prefrontal cortex were obtained using proton magnetic resonance spectroscopy.
      RESULTS: Adolescents with bipolar disorder showed significantly lower left
      ventral lateral prefrontal cortex N-acetyl aspartate levels, but post hoc
      analyses indicated that this was primarily due to increased N-acetyl aspartate
      levels in the cannabis group. The cannabis use disorder group had significantly
      higher N-acetyl aspartate levels compared to the bipolar disorder and the bipolar
      and cannabis groups (p = .0002 and p = .0002, respectively). Pearson correlations
      revealed a significant positive correlation between amount of cannabis used and N
      acetyl aspartate concentrations. CONCLUSIONS: Adolescents with cannabis use
      disorder showed higher levels of N-acetyl aspartate concentrations that were
      significantly positively associated with the amount of cannabis used; however,
      this finding was not present in adolescents with comorbid bipolar disorder.

PMID- 24729764
TI  - Letter from the editor.

PMID- 24729765
TI  - Gut bacteria in health and disease.
AB  - A new era in medical science has dawned with the realization of the critical role
      of the "forgotten organ," the gut micro-biota, in health and disease. Central to
      this beneficial interaction between the microbiota and host is the manner in
      which bacteria and most likely other microorganisms contained within the gut
      communicate with the host's immune system and participate in a variety of
      metabolic processes of mutual benefit to the host and the microbe. The advent of
      high-throughput methodologies and the elaboration of sophisticated analytic
      systems have facilitated the detailed description of the composition of the
      microbial constituents of the human gut, as never before, and are now enabling
      comparisons to be made between health and various disease states. Although the
      latter approach is still in its infancy, some important insights have already
      been gained about how the microbiota might influence a number of disease
      processes both within and distant from the gut. These discoveries also lay the
      groundwork for the development of therapeutic strategies that might modify the
      microbiota (eg, through the use of probiot-ics). Although this area holds much
      promise, more high-quality trials of probiotics, prebiotics, and other microbiota
      modifying approaches in digestive disorders are needed, as well as laboratory
      investigations of their mechanisms of action. 

PMID- 24729768
TI  - Delta virus infection: epidemiology and initiatives to intercept it.

PMID- 24729767
TI  - Patient decision tools in inflammatory bowel disease.

PMID- 24729766
TI  - Colonoscopic perforation in inflammatory bowel disease.
AB  - Colonoscopy has become the diagnostic and therapeutic modality of choice in
      patients with inflammatory bowel disease (IBD) by allowing for the assessment of
      disease extent and activity; the distinction between ulcerative colitis, Crohn's
      disease, and other differential diagnoses; the surveillance of dysplasia; and the
      delivery of treatment (eg, stricture dilation). Colonoscopy-associated
      perforation is a dreaded complication associated with significant mortality and
      morbidity. Understanding and mitigating the risks of perforation in patients with
      IBD has become an important issue with the increasing use of immunomodulators and
      biologic agents. Studies have shown that patients with IBD are at a higher risk
      for perforation from diagnostic or therapeutic endos-copy than individuals in the
      general population. Reported risk factors associated with colonoscopic
      perforation include female sex, advanced age, severe colitis, use of
      corticosteroids, presence of multiple comorbidities, and stricture dilation.
      Disease-, tech-nique-, and endoscopist-associated risk factors for perforation
      can be stratified and modified. This review, based on current available
      literature and the authors' expertise, should shed some light on the proper
      management of this challenging disease phenotype. 

PMID- 24729769
TI  - The Relationship Between the Acid Pocket and GERD.

PMID- 24729770
TI  - The use of telemedicine for performing ERCP.

PMID- 24729771
TI  - GASTRO-HEP News.

PMID- 24729772
TI  - Statin-induced cholestatic hepatitis: confirmed on rechallenge.

PMID- 24729773
TI  - Statins and liver injury.

PMID- 24729774
TI  - Esophageal obstruction as a result of isolated eosinophilic gastroenteritis.

PMID- 24729775
TI  - Eosinophilic esophagitis: are we just scratching the surface?

PMID- 24729776
TI  - Social Trust Prediction Using Heterogeneous Networks.
AB  - Along with increasing popularity of social websites, online users rely more on
      the trustworthiness information to make decisions, extract and filter
      information, and tag and build connections with other users. However, such social
      network data often suffer from severe data sparsity and are not able to provide
      users with enough information. Therefore, trust prediction has emerged as an
      important topic in social network research. Traditional approaches are primarily
      based on exploring trust graph topology itself. However, research in sociology
      and our life experience suggest that people who are in the same social circle
      often exhibit similar behaviors and tastes. To take advantage of the ancillary
      information for trust prediction, the challenge then becomes what to transfer and
      how to transfer. In this article, we address this problem by aggregating
      heterogeneous social networks and propose a novel joint social networks mining
      (JSNM) method. Our new joint learning model explores the user-group-level
      similarity between correlated graphs and simultaneously learns the individual
      graph structure; therefore, the shared structures and patterns from multiple
      social networks can be utilized to enhance the prediction tasks. As a result, we
      not only improve the trust prediction in the target graph but also facilitate
      other information retrieval tasks in the auxiliary graphs. To optimize the
      proposed objective function, we use the alternative technique to break down the
      objective function into several manageable subproblems. We further introduce the
      auxiliary function to solve the optimization problems with rigorously proved
      convergence. The extensive experiments have been conducted on both synthetic and
      real- world data. All empirical results demonstrate the effectiveness of our
      method.

PMID- 24729778
TI  - Synthesis, characterization, antimicrobial, DNA cleavage, and in vitro cytotoxic
      studies of some metal complexes of schiff base ligand derived from thiazole and
      quinoline moiety.
AB  - A novel Schiff base ligand N-(4-phenylthiazol-2yl)-2-((2-thiaxo-1,2
      dihydroquinolin-3-yl)methylene)hydrazinecarboxamide (L) obtained by the
      condensation of N-(4-phenylthiazol-2-yl)hydrazinecarboxamide with 2-thioxo-1,2
      dihydroquinoline-3-carbaldehyde and its newly synthesized Cu(II), Co(II), Ni(II),
      and Zn(II) complexes have been characterized by elemental analysis and various
      spectral studies like FT-IR, (1)H NMR, ESI mass, UV-Visible, ESR, TGA/DTA, and
      powder X-ray diffraction studies. The Schiff base ligand (L) behaves as
      tridentate ONS donor and forms the complexes of type [ML(Cl)2] with square
      pyramidal geometry. The Schiff base ligand (L) and its metal complexes have been
      screened in vitro for their antibacterial and antifungal activities by minimum
      inhibitory concentration (MIC) method. The DNA cleavage activity of ligand and
      its metal complexes were studied using plasmid DNA pBR322 as a target molecule by
      gel electrophoresis method. The brine shrimp bioassay was also carried out to
      study the in vitro cytotoxicity properties for the ligand and its metal complexes
      against Artemia salina. The results showed that the biological activities of the
      ligand were found to be increased on complexation. 

PMID- 24729779
TI  - Anti-NMDA Receptor Encephalitis in Psychiatry.
AB  - Anti-NMDA receptor encephalitis is an autoimmune disorder in which antibodies
      attack NMDA (N-methyl-D-aspartate)-type glutamate receptors at central neuronal
      synapses. Symptoms include a highly characteristic set of neurologic deficits,
      but also prominent psychiatric manifestations that often bring mental health
      professionals into the course of care. Distinct phases of illness have become
      increasingly appreciated, and include a range of psychotic symptoms early in the
      course of the disease followed by more severe fluctuations in consciousness with
      neurologic involvement, and ultimately protracted cognitive and behavioral
      deficits. Young women are most commonly impacted and an ovarian teratoma is
      sometimes associated with the syndrome. Patients respond well to immunotherapy,
      but psychiatric symptoms can be challenging to manage. We provide an up to date
      review of this disorder and highlight the role of psychiatry in diagnosis,
      symptomatology, and treatment.

PMID- 24729777
TI  - Macroergonomics in Healthcare Quality and Patient Safety.
AB  - The US Institute of Medicine and healthcare experts have called for new
      approaches to manage healthcare quality problems. In this chapter, we focus on
      macroergonomics, a branch of human factors and ergonomics that is based on the
      systems approach and considers the organizational and sociotechnical context of
      work activities and processes. Selected macroergonomic approaches to healthcare
      quality and patient safety are described such as the SEIPS model of work system
      and patient safety and the model of healthcare professional performance. Focused
      reviews on job stress and burnout, workload, interruptions, patient-centered
      care, health IT and medical devices, violations, and care coordination provide
      examples of macroergonomics contributions to healthcare quality and patient
      safety. Healthcare systems and processes clearly need to be systematically
      redesigned; examples of macroergonomic approaches, principles and methods for
      healthcare system redesign are described. Further research linking
      macroergonomics and care processes/patient outcomes is needed. Other needs for
      macroergonomics research are highlighted, including understanding the link
      between worker outcomes (e.g., safety and well-being) and patient outcomes (e.g.,
      patient safety), and macroergonomics of patient-centered care and care
      coordination.

PMID- 24729780
TI  - Activity Recognition on Streaming Sensor Data.
AB  - Many real-world applications that focus on addressing needs of a human, require
      information about the activities being performed by the human in real-time. While
      advances in pervasive computing have lead to the development of wireless and non
      intrusive sensors that can capture the necessary activity information, current
      activity recognition approaches have so far experimented on either a scripted or
      pre-segmented sequence of sensor events related to activities. In this paper we
      propose and evaluate a sliding window based approach to perform activity
      recognition in an on line or streaming fashion; recognizing activities as and
      when new sensor events are recorded. To account for the fact that different
      activities can be best characterized by different window lengths of sensor
      events, we incorporate the time decay and mutual information based weighting of
      sensor events within a window. Additional contextual information in the form of
      the previous activity and the activity of the previous window is also appended to
      the feature describing a sensor window. The experiments conducted to evaluate
      these techniques on real-world smart home datasets suggests that combining mutual
      information based weighting of sensor events and adding past contextual
      information into the feature leads to best performance for streaming activity
      recognition.

PMID- 24729781
TI  - Consistent individual differences in fathering in threespined stickleback
      Gasterosteus aculeatus.
AB  - There is growing evidence that individual animals show consistent differences in
      behavior. For example, individual threespined stickleback fish differ in how they
      react to predators and how aggressive they are during social interactions with
      conspecifics. A relatively unexplored but potentially important axis of variation
      is parental behavior. In sticklebacks, fathers provide all of the parental care
      that is necessary for offspring survival; therefore paternal care is directly
      tied to fitness. In this study, we assessed whether individual male sticklebacks
      differ consistently from each other in parental behavior. We recorded visits to
      nest, total time fanning, and activity levels of 11 individual males every day
      throughout one clutch, and then allowed the males to breed again. Half of the
      males were exposed to predation risk while parenting during the first clutch, and
      the other half of the males experienced predation risk during the second clutch.
      We detected dramatic temporal changes in parental behaviors over the course of
      the clutch: for example, total time fanning increased six-fold prior to eggs
      hatching, then decreased to approximately zero. Despite these temporal changes,
      males retained their individually-distinctive parenting styles within a clutch
      that could not be explained by differences in body size or egg mass. Moreover,
      individual differences in parenting were maintained when males reproduced for a
      second time. Males that were exposed to simulated predation risk briefly
      decreased fanning and increased activity levels. Altogether, these results show
      that individual sticklebacks consistently differ from each other in how they
      behave as parents.

PMID- 24729782
TI  - Enhanced Ca2+Entry and Tyrosine Phosphorylation Mediate Nanostructure-Induced
      Endothelial Proliferation.
AB  - Nanostructured substrates have been recognized to initiate transcriptional
      programs promoting cell proliferation. Specifically beta-catenin has been
      identified as transcriptional regulator, activated by adhesion to nanostructures.
      We set out to identify processes responsible for nanostructure-induced
      endothelial beta-catenin signaling. Transmission electron microscopy (TEM) of
      cell contacts to differently sized polyethylene terephthalate (PET) surface
      structures (ripples with 250 to 300 nm and walls with 1.5 MUm periodicity)
      revealed different patterns of cell-substrate interactions. Cell adhesion to
      ripples occurred exclusively on ripple peaks, while cells were attached to walls
      continuously. The Src kinase inhibitor PP2 was active only in cells grown on
      ripples, while the Abl inhibitors dasatinib and imatinib suppressed beta-catenin
      translocation on both structures. Moreover, Gd3+ sensitive Ca2+ entry was
      observed in response to mechanical stimulation or Ca2+ store depletion
      exclusively in cells grown on ripples. Both PP2 and Gd3+ suppressed beta-catenin
      nuclear translocation along with proliferation in cells grown on ripples but not
      on walls. Our results suggest that adhesion of endothelial cells to ripple
      structured PET induces highly specific, interface topology-dependent changes in
      cellular signalling, characterized by promotion of Gd3+ -sensitive Ca2+ entry and
      Src/Abl activation. We propose that these signaling events are crucially involved
      in nanostructure-induced promotion of cell proliferation.

PMID- 24729783
TI  - Synergistic Antiproliferative Effects of Combined gamma -Tocotrienol and PPAR
      gamma Antagonist Treatment Are Mediated through PPAR gamma -Independent
      Mechanisms in Breast Cancer Cells.
AB  - Previous findings showed that the anticancer effects of combined gamma 
      tocotrienol and peroxisome proliferator activated receptor gamma (PPAR gamma )
      antagonist treatment caused a large reduction in PPAR gamma expression. However,
      other studies suggest that the antiproliferative effects of gamma -tocotrienol
      and/or PPAR gamma antagonists are mediated, at least in part, through PPAR gamma 
      independent mechanism(s). Studies were conducted to characterize the role of PPAR
      gamma in mediating the effects of combined treatment of gamma -tocotrienol with
      PPAR gamma agonists or antagonists on the growth of PPAR gamma negative +SA
      mammary cells and PPAR gamma -positive and PPAR gamma -silenced MCF-7 and MDA-MB
      231 breast cancer cells. Combined treatment of gamma -tocotrienol with PPAR gamma
      antagonist decreased, while combined treatment of gamma -tocotrienol with PPAR
      gamma agonist increased, growth of all cancer cells. However, treatment with high
      doses of 15d-PGJ2, an endogenous natural ligand for PPAR gamma , had no effect on
      cancer cell growth. Western blot and qRT-PCR studies showed that the growth
      inhibitory effects of combined gamma -tocotrienol and PPAR gamma antagonist
      treatment decreased cyclooxygenase (COX-2), prostaglandin synthase (PGDS), and
      prostaglandin D2 (PGD2) synthesis. In conclusion, the anticancer effects of
      combined gamma -tocotrienol and PPAR gamma antagonists treatment in PPAR gamma
      negative/silenced breast cancer cells are mediated through PPAR gamma 
      independent mechanisms that are associated with a downregulation in COX-2, PGDS,
      and PGD2 synthesis. 

PMID- 24729785
TI  - Nano in implant dentistry.

PMID- 24729784
TI  - Chronic kidney disease and nonalcoholic Fatty liver disease-is there a link?
AB  - Research in recent years has led to the recognition of the importance of
      nonalcoholic fatty liver disease (NAFLD) and its relationship to the metabolic
      syndrome (MS). This has led to a growing interest in the potential prognostic
      value of NAFLD for adverse cardiovascular disease (CVD) outcome. On the other
      hand, searching for new risk factors for chronic kidney disease (CKD) development
      and progression is very important. Growing evidence suggests that the MS is an
      important factor in the pathogenesis of CKD. The best confirmation of this
      pathogenic link is hypertensive and diabetic nephropathy as the main causes of
      CKD. Furthermore, the possible link between NAFLD and CKD has also attracted
      research interest and recent data suggest an association between these two
      conditions. These findings have fuelled concerns that NAFLD may be a new and
      added risk factor for the development and progression of CKD. NAFLD and CKD share
      some important cardiometabolic risk factors and possible common
      pathophysiological mechanisms, and both are linked to an increased risk of
      incident CVD events. Therefore, common factors underlying the pathogenesis of
      NAFLD and CKD may be insulin resistance, oxidative stress, activation of rennin
      angiotensin system, and inappropriate secretion of inflammatory cytokines by
      steatotic and inflamed liver. 

PMID- 24729786
TI  - Necrostatin-1 reduces neurovascular injury after intracerebral hemorrhage.
AB  - Intracerebral hemorrhage (ICH) is the most common form of hemorrhagic stroke,
      accounting for 15% of all strokes. ICH has the highest acute mortality and the
      worst long-term prognosis of all stroke subtypes. Unfortunately, the dearth of
      clinically effective treatment options makes ICH the least treatable form of
      stroke, emphasizing the need for novel therapeutic targets. Recent work by our
      laboratory identified a novel role for the necroptosis inhibitor, necrostatin-1,
      in limiting neurovascular injury in tissue culture models of hemorrhagic injury.
      In the present study, we tested the hypothesis that necrostatin-1 reduces
      neurovascular injury after collagenase-induced ICH in mice. Necrostatin-1
      significantly reduced hematoma volume by 54% at 72 h after-ICH, as compared to
      either sham-injured mice or mice administered an inactive, structural analogue of
      necrostatin-1. Necrostatin-1 also limited cell death by 48%, reduced blood-brain
      barrier opening by 51%, attenuated edema development to sham levels, and improved
      neurobehavioral outcomes after ICH. These data suggest a potential clinical
      utility for necrostatin-1 and/or novel necroptosis inhibitors as an adjunct
      therapy to reduce neurological injury and improve patient outcomes after ICH. 

PMID- 24729787
TI  - Prevalence of Plasmodium falciparum Parasitaemia and Its Correlation with
      Haematological Parameters among HIV-Positive Individuals in Nigeria.
AB  - Malaria and HIV are the two most important health challenges of our time.
      Haematologic abnormalities are features in Plasmodium falciparum infection, and
      anaemia is a well-known outcome. The prevalence and haematological impact of P.
      falciparum parasitaemia were determined among HIV-infected individuals in
      Nigeria. Parasite detection was carried out using microscopy and Polymerase Chain
      Reaction (PCR). Haemoglobin concentration was determined using an automated
      machine while CD4+ T-cells count was analyzed using flow cytometer. Thirty-seven
      (18.5%) out of the 200 HIV individuals enrolled had malaria parasites detected in
      their blood. All the positive cases were detected by PCR while only 20 (10%) were
      detected by thick blood microscopy. The mean haemoglobin concentration and packed
      cell volume (PCV) of HIV individuals with malaria parasitaemia were lower
      compared to those without malaria parasitaemia but the difference was not
      statistically significant. Also no significant difference was observed in malaria
      positivity in respect to sex and mean CD4+ cell count. The study highlights the
      effects of P. falciparum parasitaemia on the haematologic and immune components
      of HIV individuals. 

PMID- 24729788
TI  - Impact of an educational film on parental knowledge of children with cerebral
      palsy.
AB  - Parents of children with cerebral palsy (CP) must have knowledge about the
      disease and its management to improve the outcome. This uncontrolled
      interventional trial was carried out to evaluate the parental knowledge of CP and
      assess the impact of an educational programme on it. Preset questionnaires were
      filled before and 1 week after a single session educational programme using an
      educational film. Out of a total of 53 subjects, majority (75.5%) were from lower
      socioeconomic status. Initially, none knew the correct name of child's illness;
      afterwards 45.3% could name it. When compared to previous status, there occurred
      significant improvement in the knowledge of parents after viewing the film with
      regard to knowing the cause of CP, knowing that motor involvement was predominant
      in CP, knowledge regarding curability of the disease, and knowledge about special
      schooling (P < 0.05). Change in knowledge was not related to socioeconomic or
      educational status (P > 0.05). Majority (94.3%) found the film useful and 96.2%
      learned how they could help in the management of their children. Parental
      knowledge of CP is inadequate which can be improved by incorporating such
      educational programmes in special clinics to improve management. 

PMID- 24729789
TI  - Female genital mutilation in infants and young girls: report of sixty cases
      observed at the general hospital of abobo (abidjan, cote d'ivoire, west Africa).
AB  - The practice of female genital mutilations continues to be recurrent in African
      communities despite the campaigns, fights, and laws to ban it. A survey was
      carried out in infants and young girls at the General Hospital of Abobo in Cote
      D'Ivoire. The purpose of the study was to describe the epidemiological aspects
      and clinical findings related to FGM in young patients. Four hundred nine (409)
      females aged from 1 to 12 years and their mothers entered the study after their
      consent. The results were that 60/409 patients (15%) were cut. The majority of
      the young females came from Muslim families (97%); the earlier age at FGM
      procedure in patients is less than 5 years: 87%. Amongst 409 mothers, 250 women
      underwent FGM which had other daughters cut. Women were mainly involved in the
      FGM and their motivations were virginity, chastity, body cleanliness, and fear of
      clitoris similar to penis. Only WHO types I and II were met. If there were no
      incidental events occurred at the time of the procedure, the obstetrical future
      of these young females would be compromised. With FGM being a harmful practice,
      health professionals and NGOs must unite their efforts in people education to
      abandon the procedure. 

PMID- 24729790
TI  - FPGA Based High Speed Data Acquisition System for Electrical Impedance
      Tomography.
AB  - Electrical Impedance Tomography (EIT) systems are used to image tissue bio
      impedance. EIT provides a number of features making it attractive for use as a
      medical imaging device including the ability to image fast physiological
      processes (>60 Hz), to meet a range of clinical imaging needs through varying
      electrode geometries and configurations, to impart only non-ionizing radiation to
      a patient, and to map the significant electrical property contrasts present
      between numerous benign and pathological tissues. To leverage these potential
      advantages for medical imaging, we developed a modular 32 channel data
      acquisition (DAQ) system using National Instruments' PXI chassis, along with
      FPGA, ADC, Signal Generator and Timing and Synchronization modules. To achieve
      high frame rates, signal demodulation and spectral characteristics of higher
      order harmonics were computed using dedicated FFT-hardware built into the FPGA
      module. By offloading the computing onto FPGA, we were able to achieve a
      reduction in throughput required between the FPGA and PC by a factor of 32:1. A
      custom designed analog front end (AFE) was used to interface electrodes with our
      system. Our system is wideband, and capable of acquiring data for input signal
      frequencies ranging from 100 Hz to 12 MHz. The modular design of both the
      hardware and software will allow this system to be flexibly configured for the
      particular clinical application.

PMID- 24729791
TI  - Cultural Influences on Substance Use Among Hispanic Adolescents and Young Adults:
      Findings From Project RED.
AB  - Hispanic adolescents represent a growing segment of the U.S. population. In
      addition to the typical stressors encountered during adolescence, Hispanic
      adolescents may experience acculturative stress, perceived discrimination, and
      conflicts with parents about acculturation, which can lead to maladaptive
      behaviors such as substance use. Personal cultural resources may help Hispanic
      youth cope with cultural stressors and avoid substance use, but little is known
      about how such factors affect decisions about substance use. In 2005, my research
      group began studying a group of Hispanic adolescents in Los Angeles. The
      participants completed surveys annually about cultural issues such as
      acculturation, ethnic identity, and perceived discrimination; family and peer
      relationships; and use of alcohol, tobacco, and marijuana. We found that Hispanic
      adolescents' perceptions that they were discriminated against put them at greater
      risk for substance use, and that Hispanic orientation protected the youth from
      substance use. The findings can inform the development of culturally relevant
      prevention interventions for Hispanic adolescents and emerging adults.

PMID- 24729792
TI  - Alcohol Use and Suicide Proneness in College Students: A Proposed Model.
AB  - This study was designed to assess relations among alcohol use, alcohol-related
      problems, negative-life events, depressive symptoms, and suicide proneness in a
      cross-sectional sample of undergraduate college students (N = 1100). Alcohol use
      was assumed to be causally prior to alcohol-related problems and negative life
      events, which were in turn modeled as occurring prior to depressive symptoms,
      which were in turn modeled as prior to suicide proneness. Results revealed that,
      as expected, suicide proneness was positively related to depressive symptoms,
      alcohol-related problems, negative life events, and alcohol use, and depressive
      symptoms were positively associated with alcohol-related problems and negative
      life events. Additionally, the relation between alcohol use and depressive
      symptoms was partially mediated by alcohol-related problems and negative life
      events; and the alcohol use-suicide proneness link was significantly mediated by
      alcohol-related problems, negative life events, and depressive symptoms.
      Implications are offered for the improved identification and treatment of at-risk
      young adults.

PMID- 24729793
TI  - A Health Education Intervention as the Control Condition in the CTN-0037 STRIDE
      multi-site exercise trial: Rationale and Description.
AB  - The selection of a control condition in a randomized controlled trial (RCT) is
      critical in determining the effect of the experimental treatment. While the use
      of a placebo pill can be an ideal control in pharmaceutical trials, RCTs of
      behavioral interventions present unique challenges in the selection and
      implementation of the appropriate control condition. Investigators must not only
      consider the control condition's ability to protect against threats to internal
      validity and its plausibility as a possible intervention, but must also carefully
      implement the control condition so it does not introduce bias from either the
      investigators or the participants. The purpose of this paper is to provide the
      rationale for the use of a health education intervention (HEI) as the control
      condition in the CTN-0037 Stimulant Reduction Intervention Using Dosed Exercise
      (STRIDE) trial. In this paper, we will describe the careful design of the HEI to
      ensure proper implementation and discuss alternative control conditions
      considered.

PMID- 24729794
TI  - Development of a Sensitive Assay for SERCA Activity Using FRET Detection of ADP.
AB  - Various isoforms of sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA) regulate
      Ca2+ homeostatic balance in both the heart (SERCA2a) and skeletal muscle
      (SERCA1a). Ca2+ plays a key role in these tissues as an intracellular signal that
      controls contractility. Due to its key role in the contractility cycle, SERCA is
      emerging as a promising pharmacological target to modulate heart muscle function.
      SERCA function is regulated by its endogenous inhibitor phospholamban (PLN). Upon
      binding, PLN decreases SERCA's apparent affinity for Ca2+. Therefore the
      interaction between PLN and SERCA has an important role in determining both
      physiological and pathological conditions. Quantifying the inhibitory potency of
      PLN is of great importance in understanding the pathophysiology of heart muscle.
      Traditionally, SERCA activity assays have been performed using a PK/LDH-coupled
      enzyme reaction, which suffers from limited sensitivity. We have developed a new
      SERCA activity assay based on the direct detection of the product ADP via time
      resolved FRET (TR-FRET). Under optimized conditions, our assay reduced the amount
      of SERCA required to perform the assay 1,000-fold. Inter-day reproducibility was
      shown to be excellent for SERCA preparations in either detergent (C12E8) or
      reconstituted lipids. The inhibitory effect of PLN on SERCA measured under the
      low-concentration conditions of our assay allowed us to more accurately
      investigate the binding between PLN and SERCA. Significant inhibitory effects of
      PLN were observed even at mid-nanomolar concentrations significantly lower than
      previous Kd estimates for the SERCA-PLN complex.

PMID- 24729795
TI  - Thiol-reactive amphiphilic block copolymer for coating gold nanoparticles with
      neutral and functionable surfaces.
AB  - Nanoparticles designed for biomedical applications are often coated with polymers
      containing reactive functional groups, such as -COOH and -NH2, to conjugate
      targeting ligands or drugs. However, introducing highly charged surfaces promotes
      binding of the nanoparticles to biomolecules in biological systems through ionic
      interactions, causing the nanoparticles to aggregate in biological environments
      and consequently undergo strong non-specific binding to off-target cells and
      tissues. Developing a unique polymer with neutral surfaces that can be further
      functionalized directly would be critical to develop suitable nanomaterials for
      nanomedicine. Here, we report a thiol-reactive amphiphilic block copolymer
      poly(ethylene oxide)-block-poly(pyridyldisulfide ethylmeth acrylate) (PEO-b
      PPDSM) for coating gold nanoparticles (AuNPs). The resultant polymer-coated AuNPs
      have almost neutral surfaces with slightly negative zeta potentials from -10 to 0
      mV over a wide pH range from 2 to 12. Although the zeta potential is close to
      zero we show that the PEO-b-PPDSM copolymer-coated AuNPs have both good stability
      in various physiological conditions and reduced non-specific adsorption of
      proteins/biomolecules. Because of the multiple pyridyldisulfide groups on the
      PPDSM block, these individually dispersed nanocomplexes with an overall
      hydrodynamic size around 43.8 nm can be directly functionalized via disulfide
      thiol exchange chemistry.

PMID- 24729796
TI  - Interviewer and Respondent Interactions and Quality Assessments in a Time Diary
      Study.
AB  - Systematic investigations of the cognitive challenges in completing time diaries
      and measures of quality for such interviews have been lacking. To fill this gap,
      we analyze respondent and interviewer behaviors and interviewer-provided
      observations about diary quality for a computer-assisted telephone-administered
      time diary supplement to the U.S. Panel Study of Income Dynamics. We find that
      93%-96% of sequences result in a codable answer and interviewers rarely assist
      respondents with comprehension. Questions about what the respondent did next and
      for how long appear more challenging than follow-up descriptors. Long sequences
      do not necessarily signal comprehension problems, but often involve interviewer
      utterances designed to promote conversational flow. A 6-item diary quality scale
      appropriately reflects respondents' difficulties and interviewers' assistance
      with comprehension, but is not correlated with conversational flow. Discussion
      focuses on practical recommendations for time diary studies and future research.

PMID- 24729797
TI  - Hemocompatibility and Hemodynamics of Novel Hyaluronan-Polyethylene Materials for
      Flexible Heart Valve Leaflets.
AB  - Polymeric heart valves (PHVs) hold the promise to be more durable than
      bioprosthetic heart valves and less thrombogenic than mechanical heart valves. We
      introduce a new framework to manufacture hemocompatible polymeric leaflets for HV
      (PHV) applications using a novel material comprised of interpenetrating networks
      (IPNs) of hyaluronan (HA) and linear low density polyethylene (LLDPE). We
      establish and characterize the feasibility of the material as a substitute
      leaflet material through basic hemodynamic measurements in a trileaflet
      configuration, in addition to demonstrating superior platelet response and
      clotting characteristics. Plain LLDPE sheets were swollen in a solution of
      silylated-HA, the silylated-HA was then crosslinked to itself before it was
      reverted back to native HA via hydrolysis. Leaflets were characterized with
      respect to (1) bending stiffness, (2) hydrophilicity, (3) whole blood clotting,
      and (4) cell (platelet and leukocyte) adhesion under static conditions using
      fresh human blood. In vitro hemodynamic testing of prototype HA/LLDPE IPN PHVs
      was used to assess feasibility as functional HVs. Bending stiffness was not
      significantly different from natural fresh leaflets. HA/LLDPE IPNs were more
      hydrophilic than LLDPE controls. HA/LLDPE IPNs caused less whole blood clotting
      and reduced cell adhesion compared to the plain LLDPE control. Prototype PHVs
      made with HA/LLDPE IPNs demonstrated an acceptable regurgitation fraction of 4.77
      +/- 0.42%, and effective orifice area in the range 2.34 +/- 0.5 cm2. These
      results demonstrate strong potential for IPNs between HA and polymers as future
      hemocompatible HV leaflets. Further studies are necessary to assess durability
      and calcification resistance.

PMID- 24729798
TI  - A Longitudinal Study of Well-being of Older Europeans: Does Retirement Matter?
AB  - We examine determinants of financial and subjective well-being, in particular
      poverty and depression, among older individuals in Europe. We do so using the
      2004, 2006, and 2010 waves of the Survey of Health Ageing and Retirement in
      Europe and estimating dynamic panel data and binary choice transition models. We
      find a number of common effects across financial and subjective well-being.
      Unemployment, disabilities, serious health conditions, lower education, being
      female, and not being married increase the probability of poverty or depression.
      Conversely, healthy individuals, those with higher levels of education, males,
      and married individuals have higher probabilities of exiting poverty or
      depression. The effect of retirement is of special policy interest. It turns out
      to be crucial to control for endogeneity (i.e. the possibility of reverse
      causality) of retirement. If we don't control for endogeneity, retirement appears
      to increase both the risk of poverty and of depression. Once we control for
      endogeneity using instrumental variables, these negative effects disappear and
      point to weak evidence that retirement induced through eligibility for retirement
      pensions may be protective against poverty and depression.

PMID- 24729799
TI  - Snapshots of Mixtures of Affective Experiences in a Day: Findings from the Health
      and Retirement Study.
AB  - In 2009, a representative subsample of participants in the Health and Retirement
      Study (HRS: N = 5333; Age 50-101) responded to a short day reconstruction self
      administered questionnaire that asked about their time and experiences on seven
      activities the previous day. We evaluate the quality and reliability of responses
      to this 10-minute measure of experienced well-being and compare the properties
      and correlates of three intensity-based composites reflecting mixtures of
      activity-linked affective experiences (Mean Activity-Positive Affect, Activity
      Negative Affect, and Net Affect), and a frequency-based index, Activity Affective
      Complexity, that summarizes the proportion of activities that include a mixture
      of positive and negative affective experiences regardless of intensity. On
      average, older adults reported that 36% of the activities in their day provided
      some mixture of feelings (e.g., interested and frustrated). Regression models
      revealed differential associations for the four constructs of affective well
      being with socio-demographic factors, physical and mental health, and proximal
      indicators of the day's context. We conclude that the HRS short day
      reconstruction measure is reliable and discuss the conceptual issues in
      assessing, summarizing, and interpreting the complexity of emotional experience
      in older adults.

PMID- 24729800
TI  - Identifying the Potential for Robotics to Assist Older Adults in Different Living
      Environments.
AB  - As the older adult population grows and becomes more diverse, so will their needs
      and preferences for living environments. Many adults over 65 years of age require
      some assistance [1, 2]; yet it is important for their feelings of well-being that
      the assistance not restrict their autonomy [3]. Not only is autonomy correlated
      with quality of life [4], autonomy enhancement may improve functionality [2, 5].
      The goal of this paper is to provide guidance for the development of technology
      to enhance autonomy and quality of life for older adults. We explore the
      potential for robotics to meet these needs. We evaluated older adults' diverse
      living situations and the predictors of residential moves to higher levels of
      care in the United States. We also examined older adults' needs for assistance
      with activities of daily living (ADLs), instrumental activities of daily living
      (IADLs), and medical conditions when living independently or in a long-term care
      residence. By providing support for older adults, mobile manipulator robots may
      reduce need-driven, undesired moves from residences with lower levels of care
      (i.e., private homes, assisted living) to those with higher levels of care (i.e.,
      skilled nursing).

PMID- 24729801
TI  - A rare nonvalvular left ventricular papillary fibroelastoma: A case report.
AB  - : Papillary fibroelastomas are benign cardiac tumors with high embolic potential
      typically found on the valvular surfaces of the heart. Nonvalvular papillary
      fibroelastomas are exceedingly rare. We report the case of a 66-year-old
      Caucasian male with acute bilateral basal ganglia infarctions found to have a
      mass adherent to the left ventricular septum by transesophageal echocardiography.
      The mass was identified as a rare nonvalvular cardiac papillary fibroelastoma
      based on echogenicity, pedunculated nature, and typical motion. Tissue
      characterization by cardiac magnetic resonance imaging demonstrated homogeneously
      hypo-intense signal on T2 weighted imaging and signal hyperintensity after
      administration of gadolinium contrast, confirming the fibroelastic nature of the
      mass. Surgical excision was performed via ventriculotomy and histopathologic
      examination was pathognomonic of a papillary fibroelastoma. We conclude that
      transesophageal echocardiography provides high diagnostic certainty in patients
      with cardiac papillary fibroelastomas and can reliably identify atypical
      locations of these tumors on nonvalvular surfaces. A multimodality imaging
      approach is not necessarily indicated in all patients with this condition.
      LEARNING OBJECTIVE: Papillary fibroelastomas are benign cardiac tumors with high
      embolic potential typically found on the valvular surfaces of the heart.
      Nonvalvular papillary fibroelastomas are exceedingly rare. Transesophageal
      echocardiography readily identifies nonvalvular papillary fibroelastomas based on
      echogenicity, pedunculated nature, and characteristic motion, and reliably
      differentiates them from other cardiac masses. A multimodality imaging approach
      is not indicated in all patients with this condition.

PMID- 24729802
TI  - Esophageal stents for less invasive treatment of mediastinitis.
AB  - INTRODUCTION: In spite of the progress in diagnosis and therapeutic options,
      esophageal perforation resulting in mediastinitis is a very serious condition
      with a high morbidity. AIM: To evaluate the use of esophageal stents for the
      treatment of patients suffering from mediastinitis. MATERIAL AND METHODS:
      Retrospective (2008-2012) analysis of a group of patients requiring surgical
      treatment. The evaluation was focused on the cause of perforation, stent type and
      its parameters, the surgical method used, duration of stenting and total length
      of treatment. RESULTS: In total, 16 patients were treated by stenting. All
      patients were treated with the stent being placed across the defect in the
      esophagus. Mediastinitis was accessed and drained with the aid of a thoracotomy
      or thoracolaparotomy (8 cases), or using a combination of a
      laparotomy/laparostomy and pleural drainage (5 cases). The most basic
      interventions were either pleural or external cervical drainage (3 and 1 cases,
      respectively). One patient, in whom a stricture had developed at the healed
      perforation, was subjected to esophageal resection. Four patients died. The
      average period that the stent was left in situ was 53.7 days. The average period
      of hospitalization of those patients who survived was 53.4 days. CONCLUSIONS:
      Using stents in therapy neither increased survival (mortality of 25%), nor
      decreased the length of therapy of patients once mediastinitis had developed. The
      main advantage of stenting is the preservation of the native esophagus and the
      reduced extent of surgical mediastinal drainage.

PMID- 24729804
TI  - Laparoscopic surgery of esophageal hiatus hernia - single center experience.
AB  - INTRODUCTION: Esophageal hiatal hernias are the most frequent types of internal
      hernias. This condition involves disturbance of normal functioning of the stomach
      cardiac mechanism and reflux of the gastric contents to the esophagus. AIM: To
      evaluate postoperative results in our Clinic and the comparison of these results
      to data from the literature. MATERIAL AND METHODS: One hundred and seventy-eight
      patients underwent surgery due to esophageal hiatal hernia at the Clinic of
      General, Gastroenterological and Oncological Surgery, Collegium Medicum,
      Bydgoszcz, Nicolaus Copernicus University, Torun, Poland, from 2006 to 2011. All
      operations were performed using laparoscopy. Fundoplication by means of the
      Nissen-Rossetti method was carried out in 172 patients while Toupet's and Dor's
      methods were applied in 4 and 2 patients, respectively. RESULTS: Average time of
      the surgery was 82 min (55-140 min). Conversion was performed in 4 cases. No
      serious intraoperative complications were noted. In the postoperative period,
      dysphagia was reported in 20 patients (11.2%). Postoperative wound infection was
      observed in 1 patient (0.56%). Hernias in the trocar insertion area were reported
      in 3 patients (1.68%). Ailments recurred in 6 patients. The recurrence of
      esophageal hiatal hernia was confirmed in 2 patients. Patients with recurrent
      hernia were re-operated using a laparoscopic approach. CONCLUSIONS: Laparoscopic
      surgery is a simple and effective approach for patients with gastroesophageal
      reflux symptoms due to diaphragmatic esophageal hiatus hernia. The number of
      complications is lower after laparoscopic procedures than after "open"
      operations.

PMID- 24729803
TI  - An evaluation of the knowledge of the surgical treatment of obesity among
      surgeons.
AB  - INTRODUCTION: Surgical treatment of obesity is currently the only effective
      treatment option for patients with excess body weight, especially morbid obesity
      and diseases caused by it. There are no studies evaluating the knowledge of
      surgeons in the field of bariatric surgery. AIM: To assess the knowledge of
      surgeons regarding bariatric surgery. MATERIAL AND METHODS: An anonymous
      questionnaire was conducted among 143 surgeons in 2010-2011 during local
      educational conferences. The survey consisted of 10 questions dedicated to the
      fundamental problems of the surgical treatment of obesity. RESULTS: Theoretical
      and practical knowledge connected to the so-called "epidemiological awareness" in
      the surgical treatment of obesity was possessed by 25% of the respondents.
      Knowledge of surgical techniques is known to most surgeons. Reducing the
      "oncological risk" after bariatric surgery is known to only 27% of surgeons.
      Almost 80% of surgeons indicated a necessity of their further education regarding
      the surgical treatment of obesity. CONCLUSIONS: Knowledge of Polish general
      surgeons in the surgical treatment of obesity is not high, with a high number of
      surgeons who possess knowledge of the operating technique, whereas only a quarter
      have a basic knowledge of the indication for surgical treatment. Most surgeons
      who participated in our study are awaiting educational programmes focused on this
      issue.

PMID- 24729805
TI  - Long-term outcomes of stapled hemorrhoidopexy.
AB  - INTRODUCTION: Hemorrhoidal disease is one of the commonest anorectal disorders
      worldwide. Stapled hemorrhoidopexy (SH) is a treatment modality associated with
      low postoperative pain and early mobilization. AIM: To assess long-term outcomes
      after SH. MATERIAL AND METHODS: All 326 patients who underwent SH in 1999-2003
      were invited by mail to participate. For each patient we analyzed their medical
      records, and conducted a questionnaire survey and a digital rectal examination.
      RESULTS: Only 91 patients attended the final examination and the mean +/- SD
      follow-up time was 8.7 +/-1.2 years. Recurrences were diagnosed in one third of
      the 91 subjects. There were correlations between recurrences and: the duration of
      disease (p = 0.047); female gender (p = 0.037); and childbirth (vaginal delivery)
      (p = 0.026). Sixty-seven patients (73.6%) were satisfied with the outcomes. In
      the group of dissatisfied patients symptoms such as pain (p = 0.0001), burning (p
      = 0.0002) and itching (p = 0.014) were most common. Long-term outcomes were good
      with 75% and 88% reductions in pain sensation and severe and moderate
      hemorrhoidal bleeding. Pruritus, burning and discomfort resolved in more than 50%
      of patients. Flatus incontinence, fecal incontinence, or soiling occurred in 21%,
      11%, and 32% of patients. CONCLUSIONS: Long-term results of stapled
      hemorrhoidopexy are satisfactory in most patients. The 36% recurrence rate
      correlates with the degree of hemorrhoidal prolapse before the operation,
      duration of the disease, female gender, and previous vaginal delivery.

PMID- 24729806
TI  - Laser Doppler imaging as a tool in the burn wound treatment protocol.
AB  - INTRODUCTION: The main treatment of burns is early excision of injured tissues.
      AIM: TO COMPARE TWO DIFFERENT METHODS OF EXAMINATION OF BURNED PATIENTS: clinical
      burn depth examination (CDE) and laser Doppler imaging (LDI). MATERIAL AND
      METHODS: A prospective randomized study of 57 burn patients treated in 2009-2011
      was carried out. The burned patients were randomized into a CDE group and an LDI
      group. The CDE and LDI scan were performed 72 h after injury, with the second and
      third CDE and LDI scan on the 7(th) and 14(th) day after the burn. Age, sex,
      length of inpatient stay, cost of burn treatment, burn depth, cause and
      localization of the burns were analyzed between the two groups. RESULTS: Fifty
      seven patients were treated during 2 years. Thirty-two patients were in the CDE
      group and 25 patients were in the LDI group. Most of the patients were male (45
      male vs. 12 female, p < 0.001). The age was similar between the males and the
      females (female: 46.4 +/-16.9 years vs. male: 46.3 +/-12.5 years; p = 0.11). The
      mean length of stay in hospital was significantly higher in the CDE group (47 +/
      34.4 day vs. 25 +/-10.8 day; p = 0.005). The mean cost of treatment of burned
      patients was significantly higher in the CDE group. CONCLUSIONS: The length of
      stay and cost of treatment of burn patients depends upon early diagnosis of the
      deep burns and well-timed surgical treatment of burn wounds.

PMID- 24729807
TI  - Does the length of the biliary limb influence medium-term laboratory remission of
      type 2 diabetes mellitus after Roux-en-Y gastric bypass in morbidly obese
      patients?
AB  - INTRODUCTION: The Roux-en-Y gastric bypass (RYGB) is an effective treatment of
      morbid obesity leading to type 2 diabetes mellitus (T2DM) resolution. However,
      evidence demonstrates that standard limb lengths can have a limited impact on
      long-term weight loss and durable T2DM remission. AIM: The authors evaluated the
      impact of biliary limb (BL) length on the T2DM laboratory markers in 2-year
      follow-up. MATERIAL AND METHODS: The data of 93 obese patients with T2DM who
      underwent RYGB between 2008 and 2010 were collected from prospectively designed
      database. The length of BL was standard in one group of 51 patients (S-BL: 50-75
      cm) and longer in another group of 42 patients (L-BL: 100-150 cm). The laboratory
      parameters defining T2DM remission - fasting plasma glucose (FPG) and
      glycosylated hemoglobin (HbA1c) - were measured 3, 6, 12 and 24 months after
      surgery. RESULTS: The average level of FPG and HbA1c remained non-diabetic 24
      months after the RYGB in both groups. A statistical difference was not observed
      in direct FPG, HbA1c, DeltaFPG and DeltaHbA1c comparisons at any follow-up point.
      However, a significantly higher proportion of patients in L-BL than in S-BL
      reached the laboratory remission criteria without anti-diabetic medicaments.
      Additional analysis revealed a strong correlation between the measured T2DM
      parameters and length of the common limb (CL) in both groups. CONCLUSIONS: A
      longer BL can intensify the anti-diabetic effect of RYGB. The length of CL rather
      than BL influences the medium-term T2DM remission. Long-term observation is
      needed to fully assess whether introduced technical aspects of RYGB provide a
      durable effect of T2DM resolution.

PMID- 24729808
TI  - Transanal endoscopic microsurgery combined with endoscopic posterior mesorectum
      resection in the treatment of patients with T1 rectal cancer - 3-year results.
AB  - INTRODUCTION: Rectum-sparing transanal endoscopic microsurgery (TEM) is a well
      established treatment for T1 rectal cancer (RC). However, it is associated with
      an increased rate of local recurrence in comparison with extended resection. In
      most cases this failure is linked to inappropriate case selection and the
      presence of clinically non-detectable metastases in the regional lymph nodes.
      Endoscopic posterior mesorectal resection (EPMR) makes it possible to remove the
      relevant lymphatic drainage of the lower third of the rectum in a minimally
      invasive way, which in turn can help in adequate tumor staging. AIM: To evaluate
      the long-term clinical results and influence of combined TEM and EPMR treatment
      on the anorectal functions. MATERIAL AND METHODS: Ten consecutive patients with
      T1 RC were operated on using TEM and EPMR as a two-stage procedure between 2007
      and 2009. RESULTS: After a median follow-up of 42.6 (range: 36-80) months, none
      of our patients complained of symptoms of incontinence apart from one female
      patient with gas incontinence diagnosed preoperatively. There was no
      statistically significant difference in basal anal pressure, squeeze anal
      pressure, high pressure zone length or fecal continence assessed using the Fecal
      Incontinence Severity Index before and in follow-up months after the procedure.
      Postoperative morbidity consisted of one hematoma formation and one male patient
      complaining about sexual dysfunction until 6 months postoperatively. There was no
      evidence of locoregional recurrence. CONCLUSIONS: Endoscopic posterior mesorectal
      resection in combination with TEM appears to be safe, feasible and with no impact
      on the basic anorectal functions in the 3-year follow-up.

PMID- 24729809
TI  - Laparoscopic sleeve gastrectomy without over-sewing of the staple line is
      effective and safe.
AB  - INTRODUCTION: Laparoscopic sleeve gastrectomy (LSG) is a bariatric procedure with
      very good long-term weight-reducing and metabolic effects. AIM: Here we report 6
      years' experience with LSG performed in morbidly obese patients by one surgical
      team focusing on the impact of the degree of sleeve restriction and safety of the
      procedure without over-sewing the staple line. MATERIAL AND METHODS: From 2006 to
      2012, 207 morbid obese patients with average age of 43.4 years and average body
      mass index 44.9 kg/m(2) underwent LSG without over-sewing the staple line. The
      complete 5- and 3-year follow-up is recorded in 59 and 117 patients with
      prospective data collection at 3, 6, 9, 12, 18, 24, 36, 42 and 60 months after
      LSG. Group 1 patients operated in 2006-2008 had smaller sleeve restriction. Group
      2 patients operated in 2009-2012 had major sleeve restriction. All procedures
      were performed without over-sewing of the staple line. RESULTS: The average
      %EBMIL (excess body mass index loss) in group 1 patients with minor sleeve
      restriction reached 54.1% and average %EWL (excess weight loss) was 50.8% while
      in group 2 with major sleeve restriction the average %EBMIL reached 69.7% and
      average %EWL was 66.8%. Final weight reduction was significantly higher in group
      2 patients compared to group 1 patients with smaller sleeve restriction. Out of
      49 patients with preoperatively diagnosed T2DM (type 2 diabetes mellitus) was
      completely resolved in 70.8%. Pre-operatively diagnosed hypertension normalized
      in 64.2%, improved in 23.2%, and remained unchanged in 12.6% of patients.
      CONCLUSIONS: Carefully performed LSG without over-sewing the staple line is
      feasible and safe. A better weight-reducing effect was present in patients with
      major sleeve restriction.

PMID- 24729810
TI  - Laparoscopic inguinal hernia repair in children using the percutaneous internal
      ring suturing technique - own experience.
AB  - INTRODUCTION: Percutaneous internal ring suturing (PIRS) is a method of
      laparoscopic herniorrhaphy, i.e. percutaneous closure of the internal inguinal
      ring under the control of a telescope placed in the umbilicus. AIM: To evaluate
      the usefulness of the PIRS technique. MATERIAL AND METHODS: Fifty-five children
      (39 girls and 16 boys) underwent surgery using this method in our institution
      between 2008 and 2010. RESULTS: In 10 cases the presence of an open inguinal
      canal on the opposite side was also noted during surgery, and umbilical hernia
      was recognized in 2 patients. In 5 cases it was necessary to convert to the open
      surgery because of the inability to continue the laparoscopic procedure. In 1
      case, male pseudohermaphroditism was diagnosed during surgery. Recurrent inguinal
      hernia required a conventional method of surgery in 1 child. Other children did
      not exhibit the characteristics of hernia recurrence. The inguinal canals were
      followed up with postoperative ultrasound examination in 29 children. In 23
      children, the ultrasound examination showed no dilatation of the inguinal canal.
      In the other 6 children dilatation of the inguinal canal or the presence of fluid
      within the inguinal canal was observed during ultrasound. In 6 children symptoms
      such as swelling and soreness around the inguinal canal developed within 3 to 6
      months after surgery. CONCLUSIONS: Inguinal hernia surgery using the PIRS
      procedure is an alternative, effective, minimally invasive method of surgery.
      Visualization of the peritoneal cavity allows for detection of other
      abnormalities, as well as for performing other procedures during the same session
      (such as closing the contralateral inguinal canal or umbilical hernia surgery).

PMID- 24729811
TI  - Own experiences of endoscopic self-expandable stent placement for malignant
      colorectal ileus.
AB  - INTRODUCTION: Acute low neoplasm ileus requires emergency surgery. Nowadays there
      are increased numbers of patients with comorbidities, which causes higher risk of
      intra- and postoperative complications. AIM: To evaluate the clinical usefulness
      of endoscopic self-expandable stent placement for malignant colorectal ileus.
      MATERIAL AND METHODS: Twenty-one patients (8 women and 13 men), mean age 66.7
      years, with low neoplasm obstruction, underwent endoscopic stenting of the
      stricture. This procedure was performed as a bridge to the surgery especially for
      high-risk patients. Eight of them had coagulation system impairment, 5 severe
      metabolic disorders, 4 circulatory insufficiency, 3 severe malnutrition and 1
      patient undiagnosed synchronic rectal tumor. In 10 patients cancer was located in
      the sigmoid colon, in 7 in the rectum, in 2 in the ascending colon, and the
      transverse and ascending colon was involved in another 2 patients. RESULTS: All
      21 patients (100%) underwent endoscopic stenting successfully. There were no
      complications after stent placement. The authors underline that placement of
      expandable metallic stents for patients with malignant colon obstruction with
      acute ileus is a safe and effective method. It gives an opportunity for quick
      balance of fluid, electrolyte, and the coagulation system and improvement of
      efficiency of the circulatory and respiratory system. CONCLUSIONS: Endoscopic
      treatment of ileus helps precisely estimate tumor advancement and gives the
      possibility of a single stage radical surgical procedure.

PMID- 24729812
TI  - Clinical value of extended pelvic lymph node dissection in patients subjected to
      radical prostatectomy.
AB  - INTRODUCTION: Extended pelvic lymph node dissection (ePLND) is advised to
      complement radical prostatectomy (RP) in intermediate and high risk prostate
      cancer patients. AIM: To assess the risk of nodal involvement in patients
      subjected to laparoscopic radical prostatectomy and to characterize the group of
      patients with lymph node (LN) metastases. MATERIAL AND METHODS: Data of patients
      subjected to laparoscopic radical prostatectomy with ePLND between February 2011
      and June 2013 were analyzed. The LN that were removed included presacral nodes,
      common, external and internal iliac nodes and obturator ones. RESULTS: Mean
      number of removed LNs was 19. Metastases within LN were found in 13 (16.6%)
      patients. In comparison to those without LN involvement, patients who were found
      to have LN metastases had a greater number of positive biopsy cores (3.7 vs. 5.3,
      p < 0.01), maximum percentage of cancer in biopsy core (47.0 vs. 67.6, p < 0.01),
      greater biopsy and specimen Gleason scores (7.0 vs. 7.7 and 7.0 vs. 7.8) and more
      frequently advanced clinical and pathological stage. The most frequent landing
      sites of prostate cancer were obturator and presacral nodes (100% and 38%).
      Eleven patients (85%) among those with positive LN had locally advanced disease.
      CONCLUSIONS: The risk of LN metastases in intermediate and high risk prostate
      cancer patients is significant. Therefore, if radical prostatectomy is chosen,
      ePLND should be performed. The majority of patients with involvement of pelvic LN
      have locally advanced disease which would refer them to adjuvant radiation if
      managed without nodal dissection.

PMID- 24729813
TI  - Surgical management of gastrointestinal stromal tumors: a single center
      experience.
AB  - INTRODUCTION: Gastrointestinal stromal tumors (GISTs) are the most common
      mesenchymal tumors of the gastrointestinal (GI) tract. Although the therapy
      targeted at inhibiting tyrosine kinases has shown dramatic results in metastatic
      and inoperable GISTs, the mainstay of treatment in primary localized forms
      remains surgical resection. AIM: To provide an overview of our experience of GIST
      diagnosis and management, with emphasis on comparison of minimally invasive and
      open surgical resection for primary GISTs. MATERIAL AND METHODS: We
      retrospectively reviewed the medical records of all patients who underwent
      surgical removal of GISTs from 2008 to 2012. Patient demographics, clinical data,
      surgery, complications, histopathological data and clinical course were analyzed.
      RESULTS: Forty-four patients were identified. Average age at diagnosis was 63
      years. Minimally invasive (MIS) and open surgery (OS) were each attempted in 22
      (50.0%) patients. Laparoscopic removal was performed in 20, laparoendoscopic in
      1, and laparoscopy-assisted endoscopic removal in 1. Conversion to an open
      procedure was performed in 4 (18.2%). We found significant differences in
      postoperative length of stay (8.5 days vs. 10.1 days, p < 0.001) and tumor size
      (2.93 cm vs. 5.78 cm, p = 0.018) between MIS and OS groups, respectively.
      CONCLUSIONS: Laparoscopic removal is safe and effective for GISTs not exceeding 6
      cm. Gastroesophageal junction and cardia GISTs require careful preoperative
      evaluation and planning to remove safely. We recommend avoiding laparoscopic
      removal of these tumors due to the high rate of conversion (100.0%) to an open
      procedure. Laparoendoscopic surgical approach is an appropriate technique for
      removal of small-sized intraluminal benign GISTs not involving the muscularis
      propria layer.

PMID- 24729814
TI  - The influence of laparoscopic vs. open gastric bypass on hemodynamic function in
      morbidly obese patients during general anesthesia.
AB  - INTRODUCTION: The open or laparoscopic procedure has an important influence on
      the hemodynamic function in morbidly obese patients undergoing bariatric surgery.
      The anesthesiologist and surgeon must be aware of changes in hemodynamic
      performance during laparoscopy or laparotomy under general anesthesia. AIM: TO
      EVALUATE AND COMPARE THE HEMODYNAMICS IN TWO TYPES OF SURGERY: open vs.
      laparoscopic. MATERIAL AND METHODS: After obtaining the local ethics committee
      approval 60 morbidly obese (MO) patients (body mass index >= 40 kg/m(2))
      scheduled for elective open or laparoscopic Roux-en-Y gastric bypass were
      included. Patients were allocated to study groups depending on the scheduled type
      of surgery (no randomization). General anesthesia with sevoflurane was performed.
      The hemodynamic parameters were recorded using a HemoSonic 100 device - a
      transesophageal Doppler measurement at time points: T1 - initial, T2 - after
      creating pneumoperitoneum (group PP) or opening the abdomen (group OP). RESULTS:
      Complete data were collected on 28 patients in group LP and 21 in group OP. There
      was no statistical difference between groups in demographic data. At time point
      T2 in both groups the parameters stroke volume, peak velocity and cardiac index
      decreased, and total systemic vascular resistance increased significantly
      compared to T1 (p < 0.05). In group LP the parameters cardiac output and
      acceleration (Acc) of blood decreased significantly compared to T1 (p < 0.05).
      There were significant differences between groups (p > 0.05) in cardiac output,
      total systemic vascular resistance and Acc, which were significantly higher in
      the OP group. In both groups mean arterial pressure increased and heart rate
      stayed similar to T1 with no significant difference (p > 0.05). No complications
      were observed. CONCLUSIONS: Pneumoperitoneum has a significant negative influence
      on hemodynamic function during laparoscopic bariatric procedures compared to open
      surgery in morbidly obese patients.

PMID- 24729815
TI  - New surgical modification of fascial closure following endovascular aortic
      pathology repair.
AB  - INTRODUCTION: There are clear benefits of percutaneous versus open femoral access
      for endovascular aortic pathology repair. All closing devices commercially
      available are expensive. Surgical closure of the femoral artery risks potential
      prolonged wound healing and as a consequence longer hospital stay. Fascial
      closure is a technique that remains an interesting option. AIM: To evaluate the
      efficacy of the surgical modification of hemostasis control after endovascular
      repair of aortic pathology. MATERIAL AND METHODS: One hundred sixteen common
      femoral arteries in a group of 58 patients underwent a minimally invasive
      procedure. Patients suffering from abdominal, thoracic aorta aneurysms, acute
      thoracic aorta type B dissections and traumatic aortic injury were treated.
      RESULTS: A 1-year period of experience in fascial closure of 116 common femoral
      arteries was presented in the group of 58 patients undergoing endovascular
      interventions. Five intraoperative complications were observed and one late.
      Three primary failures were due to hemorrhage in three arteries, one required
      open repair and two additional compression after the procedure. Two cases of limb
      ischemia required surgical correction of artery closure. One limb ischemia was
      detected 4 weeks later, and was treated conservatively. At 1 year, 92 fascial
      closures (80%) were in the follow-up and 24 (20%) were lost to follow-up.
      CONCLUSIONS: This new modification of fascial closure is a safe and cheap method
      of arterial closure following endovascular repair of selected aortic pathologies.
      The usage of two suture lines makes this procedure easy and quick. Fascial
      closure technique is comparable to other techniques in terms of success and
      complication rates.

PMID- 24729816
TI  - Use of endoscopic lithotripsy technique in the treatment of intestinal neobladder
      lithiasis performed by means of the VIP method.
AB  - We describe a case of minimally invasive endoscopic technique used in the
      treatment of a large calculus in the intestinal neobladder. The patient had the
      intestinal bladder created by means of the Vesica Ileale Padovana (VIP) method
      because of an invasive urothelial carcinoma. The use of the pneumatic
      lithotripter, inserted through the urethra into the intestinal neobladder,
      enabled crushing of the calculus and safe evacuation of the resulting small
      fragments. The endoscopic technique described enabled avoidance of a technically
      difficult surgical treatment and allowed for rapid return of the patient to
      complete health. In our opinion this is the best method of treatment. 

PMID- 24729817
TI  - Foraminoplastic transfacet epidural endoscopic approach for removal of
      intraforaminal disc herniation at the L5-S1 level.
AB  - Transforaminal endoscopic disc removal in the L5-S1 motion segment of the lumbar
      spine creates a technical challenge due to anatomical reasons and individual
      variability. The majority of surgeons prefer a posterior classical or minimally
      invasive approach. There is only one foraminoplastic modification of the
      technique in the literature so far. In this paper we present a new technique with
      a foraminoplastic transfacet approach that may be suitable in older patients with
      advanced degenerative disease of the spine. 

PMID- 24729818
TI  - Multi-procedure management in an eyeglasses-related open globe injury.
AB  - We present a case of successful multi-procedure management of a patient with an
      open globe injury. A 47-year-old man sustained an injury to his left eye caused
      by glass fragments of his own spectacles shattered while he was protecting an
      unknown woman from physical assault at a bus stop. Over a span of 65 months the
      patient underwent multiple procedures including primary wound repair, penetrating
      keratoplasty combined with extracapsular cataract extraction, neodymium: YAG
      laser capsulotomy, and laser-assisted subepithelial keratectomy (LASEK), and had
      a successfully treated episode of corneal graft rejection. This sequence of
      treatment substantially improved his left eye vision from hand movements at the
      time of admission to 0.9-0.5 * 90 at the last follow-up nearly 10 years after the
      trauma. Proper initial surgical management of an open globe injury can create the
      possibility for virtually complete vision restoration. 

PMID- 24729819
TI  - Combined minimally invasive management of infected pancreatic necrosis: a case
      report.
AB  - Infected necrosis is a potentially fatal complication of necrotizing
      pancreatitis. Open surgical debridement is the mainstay management of infected
      pancreatic necrosis. Over the last decade minimally invasive techniques have been
      increasingly used for the treatment of infected pancreatic necrosis and their
      results are encouraging. However, the optimal technique of minimal access
      necrosectomy and the timing of intervention have not been established yet.
      Patients with septic complications of acute pancreatitis represent a challenging
      group which requires individualized management often involving numerous
      techniques. We report a case of a 52-year-old patient in whom 3 minimally
      invasive techniques were needed for complete recovery. 

PMID- 24729820
TI  - Two-stage bilateral laparoscopic adrenalectomy for large pheochromocytomas.
AB  - A 66-year-old Lithuanian female patient with a history of hypertension was
      diagnosed with bilateral adrenal tumors during a routine sonoscopy. Scintigraphy
      with metaiodobenzylguanidine and computed tomography scan revealed right
      130/116/93 mm and left 85/61/53 mm pheochromocytomas. The patient suffered from
      hypertension with blood pressure over 240/100 mm Hg and heartbeat disturbances.
      Blood adrenaline levels exceeded the norm 10-fold. After possible spread of
      tumors was rejected, laparoscopic transperitoneal adrenalectomy was planned in 2
      stages, starting on the right then followed by the left side. After preoperative
      treatment with adrenoblockers, 2-stage bilateral laparoscopic adrenalectomy was
      performed. 13 cm * 12 cm * 9.5 cm right adrenal and, 3 months later, 8.5 cm * 8
      cm * 6 cm left adrenal pheochromocytomas were removed. Histologically - radical
      extirpation, pheochromocytomas with possible malignant potential. Stable
      remission of hypertension was achieved postoperatively. Laparoscopic
      transperitoneal adrenalectomy is a safe and feasible method of treatment of large
      benign and possible malignant, but noninvasive pheochromocytomas. 

PMID- 24729821
TI  - Laparoscopic horseshoe kidney isthmusectomy: four case reports.
AB  - Horseshoe kidney is a congenital defect of the urinary tract that occurs in 0.25%
      of the general population. The indications for division of the isthmus of
      horseshoe kidney are controversial, and if done, it is during the concomitant
      removal of additional defects accompanying horseshoe kidney. The aim of this
      study was to evaluate the results of isthmusectomy of horseshoe kidney using
      laparoscopy. This paper presents cases of 4 patients who underwent isthmusectomy,
      dismembered pyeloplasty, and stone removal using laparoscopy. All patients were
      operated on by a transperitoneal approach using 4 trocars. In 3 patients, we cut
      the renal isthmus by means of bipolar scissors and then we closed the renal
      parenchyma using two continuous hemostatic Vicryl 1-0 stitches. In 1 patient, an
      endostapler was used for isthmusectomy. The total operative time ranged from 4.5
      h to 5.5 h including simultaneous dismembered pyeloplasty in 3 patients. Blood
      loss ranged from 40 ml to 300 ml. Use of the endostapler greatly facilitated the
      procedure. There were no complications either during or after the procedure. In
      all patients, mobilization and oral nutrition were included on the first or
      second day. On the third day, all patients were ready to be discharged from the
      hospital. Long-term follow-up after treatment showed good results in all
      patients. Laparoscopy is an alternative to open surgery, particularly in the
      correction of congenital defects of the urinary tract. Although the indications
      for division of the isthmus of horseshoe kidney are controversial, laparoscopic
      technique in isthmusectomy is safe for patients, as shown by our results. 

PMID- 24729822
TI  - Innovative video capsule endoscopy for detection of ubiquitously elongated small
      intestinal villi in Cronkhite-Canada syndrome.
AB  - Cronkhite-Canada syndrome (CCS) is a rare non-familial disorder with multiple
      gastrointestinal polyps and ectodermal changes. Adenomatous and carcinomatous
      changes have been reported. Video capsule endoscopy is a useful non-invasive tool
      to reveal polypoid lesions of the gastrointestinal tract suspicious for
      malignancy. We report a case of a patient with CCS with excessively elongated
      intestinal villi resembling dense sea grass under water as well as multiple
      polyps of the intestinal mucosa revealed by video capsule endoscopy. This report
      presents for the first time small bowel video sequences of CCS qualifying video
      capsule endoscopy for screening purposes and early detection of malignancy. 

PMID- 24729823
TI  - Case Management Reduces Drinking During Pregnancy among High Risk Women.
AB  - AIM: Estimate the efficacy of Case Management (CM) for women at high risk for
      bearing a child with Fetal Alcohol Spectrum Disorders (FASD). DESIGN: Women were
      recruited from antenatal clinics and engaged in 18 months of CM. SETTING: A South
      African community with a subculture of heavy, regular, weekend, recreational
      drinking and high documented rates of FASD. PARTICIPANTS: Forty-one women who
      were high risk for bearing a child with FASD. MEASURES: Statistical analysis of
      trends in drinking and other risk factors. FINDINGS: At intake 87.8% were
      pregnant, most had previous alcohol-exposed pregnancies, most/all of their
      friends drink alcohol (67.5%), and 50.0% had stressful lives. CM was particularly
      valuable for pregnant women, as statistically significant reductions in alcohol
      risk were obtained for them in multiple variables: total drinks on weekends after
      six months of CM (p = .026) and estimated peak blood alcohol concentration (BAC)
      at six (p < .001) and 18 months (p < .001). For participants completing 18 months
      of CM, AUDIT scores improved significantly by 6-month follow-up (from 19.8 to
      9.7, p = .000), and even though rising at 12 and 18 months, AUDIT scores indicate
      that problematic drinking remained statistically significantly lower than
      baseline throughout CM. Happiness scale scores correlated significantly with
      reduced drinking in most time periods. CONCLUSIONS: An enduring change in
      drinking behavior is difficult in this social setting. Yet, CM provided by
      skilled and empathic case managers reduced maternal drinking at critical times,
      and therefore, alcohol exposure levels to the fetus.

PMID- 24729824
TI  - JOINT ANALYSIS OF SNP AND GENE EXPRESSION DATA IN GENETIC ASSOCIATION STUDIES OF
      COMPLEX DISEASES.
AB  - Genetic association studies have been a popular approach for assessing the
      association between common Single Nucleotide Polymorphisms (SNPs) and complex
      diseases. However, other genomic data involved in the mechanism from SNPs to
      disease, e.g., gene expressions, are usually neglected in these association
      studies. In this paper, we propose to exploit gene expression information to more
      powerfully test the association between SNPs and diseases by jointly modeling the
      relations among SNPs, gene expressions and diseases. We propose a variance
      component test for the total effect of SNPs and a gene expression on disease
      risk. We cast the test within the causal mediation analysis framework with the
      gene expression as a potential mediator. For eQTL SNPs, the use of gene
      expression information can enhance power to test for the total effect of a SNP
      set, which are the combined direct and indirect effects of the SNPs mediated
      through the gene expression, on disease risk. We show that the test statistic
      under the null hypothesis follows a mixture of chi2 distributions, which can be
      evaluated analytically or empirically using the resampling-based perturbation
      method. We construct tests for each of three disease models that is determined by
      SNPs only, SNPs and gene expression, or includes also their interactions. As the
      true disease model is unknown in practice, we further propose an omnibus test to
      accommodate different underlying disease models. We evaluate the finite sample
      performance of the proposed methods using simulation studies, and show that our
      proposed test performs well and the omnibus test can almost reach the optimal
      power where the disease model is known and correctly specified. We apply our
      method to re-analyze the overall effect of the SNP-set and expression of the
      ORMDL3 gene on the risk of asthma.

PMID- 24729825
TI  - Self-Reported Experiences of Discrimination and Cardiovascular Disease.
AB  - Researchers have long speculated that exposure to discrimination may increase
      cardiovascular disease (CVD) risk but compared to other psychosocial risk
      factors, large-scale epidemiologic and community based studies examining
      associations between reports of discrimination and CVD risk have only emerged
      fairly recently. This review summarizes findings from studies of self-reported
      experiences of discrimination and CVD risk published between 2011-2013. We
      document the innovative advances in recent work, the notable heterogeneity in
      these studies, and the considerable need for additional work with objective
      clinical endpoints other than blood pressure. Implications for the study of
      racial disparities in CVD and clinical practice are also discussed.

PMID- 24729826
TI  - Current Insights into the Joint Genetic Basis of Type 2 Diabetes and Coronary
      Heart Disease.
AB  - The large-scale genome-wide association studies conducted so far identified
      numerous allelic variants associated with type 2 diabetes (T2D), coronary heart
      disease (CHD) and related cardiometabolic traits. Many T2D- and some CHD-risk
      loci are also linked with metabolic traits that are hallmarks of insulin
      resistance (lipid profile, abdominal adiposity). Chromosome 9p21.3 and 2q36.3 are
      the most consistently replicated loci appearing to share genetic risk for both
      T2D and CHD. Although many glucose- or insulin-related trait variants are also
      linked with T2D risk, none of them is associated with CHD. Hence, while T2D and
      CHD are strongly clinically linked together, further ongoing analyses are needed
      to clarify the existence of a shared underlying genetic signature of these
      complex traits. The present review summarizes an updated picture of T2D-CHD
      genetics as of 2013, aiming to provide a platform for targeted studies dissecting
      the contribution of genetics to the phenotypic heterogeneity of T2D and CHD.

PMID- 24729827
TI  - The Global Role of the World Health Organization.
AB  - The 21st century global health landscape requires effective global action in the
      face of globalization of trade, travel, information, human rights, ideas, and
      disease. The new global health era is more plural, comprising a number of key
      actors, and requiring more coordination of effort, priorities and investments.
      The World Health Organization (WHO) plays an essential role in the global
      governance of health and disease; due to its core global functions of
      establishing, monitoring and enforcing international norms and standards, and
      coordinating multiple actors toward common goals. Global health governance
      requires WHO leadership and effective implementation of WHO's core global
      functions to ensure better effectiveness of all health actors, but achieving this
      global mission could be hampered by narrowing activities and budget reallocations
      from core global functions.

PMID- 24729829
TI  - Leaking Underground Storage Tanks and Environmental Injustice: Is There a Hidden
      and Unequal Threat to Public Health in South Carolina?
AB  - There are approximately 590,000 underground storage tanks (USTs) nationwide that
      store petroleum or hazardous substances. Many of these tanks are leaking, which
      may increase the risk of exposure to contaminants that promote health problems in
      host neighborhoods. Within this study, we assessed disparities in the spatial
      distribution of leaking underground storage tanks (LUSTs) based on socioeconomic
      status (SES) and race/ethnicity in South Carolina (SC). Chi-square tests were
      used to evaluate the difference in the proportion of populations who host a LUST
      compared to those not hosting a LUST for all sociodemographic factors. Linear
      regression models were applied to examine the association of distance to the
      nearest LUST with relevant sociodemographic measures. As percent black increased,
      the distance (both in kilometers and miles) to the nearest LUST decreased.
      Similar results were observed for percent poverty, unemployment, persons with
      less than a high school education, blacks in poverty, and whites in poverty.
      Furthermore, chi-square tests indicated that blacks or non-whites or people with
      low SES were more likely to live in LUST host areas than in non-host areas. As
      buffer distance increased, percent black and non-white decreased. SES variables
      demonstrated a similar inverse relationship. Overall, burden disparities exist in
      the distribution of LUSTs based on race/ethnicity and SES in SC.

PMID- 24729830
TI  - Semi-supervised clustering methods.
AB  - Cluster analysis methods seek to partition a data set into homogeneous subgroups.
      It is useful in a wide variety of applications, including document processing and
      modern genetics. Conventional clustering methods are unsupervised, meaning that
      there is no outcome variable nor is anything known about the relationship between
      the observations in the data set. In many situations, however, information about
      the clusters is available in addition to the values of the features. For example,
      the cluster labels of some observations may be known, or certain observations may
      be known to belong to the same cluster. In other cases, one may wish to identify
      clusters that are associated with a particular outcome variable. This review
      describes several clustering algorithms (known as "semi-supervised clustering"
      methods) that can be applied in these situations. The majority of these methods
      are modifications of the popular k-means clustering method, and several of them
      will be described in detail. A brief description of some other semi-supervised
      clustering algorithms is also provided.

PMID- 24729828
TI  - Global Health Governance at a Crossroads.
AB  - This review takes stock of the global health governance (GHG) literature. We
      address the transition from international health governance (IHG) to global
      health governance, identify major actors, and explain some challenges and
      successes in GHG. We analyze the framing of health as national security, human
      security, human rights, and global public good, and the implications of these
      various frames. We also establish and examine from the literature GHG's major
      themes and issues, which include: 1) persistent GHG problems; 2) different
      approaches to tackling health challenges (vertical, horizontal, and diagonal); 3)
      health's multisectoral connections; 4) neoliberalism and the global economy; 5)
      the framing of health (e.g. as a security issue, as a foreign policy issue, as a
      human rights issue, and as a global public good); 6) global health inequalities;
      7) local and country ownership and capacity; 8) international law in GHG; and 9)
      research gaps in GHG. We find that decades-old challenges in GHG persist and GHG
      needs a new way forward. A framework called shared health governance offers
      promise.

PMID- 24729831
TI  - Family Systems Theory and Obesity Treatment: Applications for Clinicians.
AB  - Family-based approaches are recommended for the treatment of pediatric obesity,
      although most of the literature describes programs that only include the
      identified child and one parent in the treatment process. As a result, the
      clinical application of research protocols in nutrition settings may be
      inadequate; multiple representations of a "family" will be encountered in the
      clinical environment. Mental health professionals, particularly those who work
      with children, often engage families in psychotherapy. Developing an
      understanding of their methods may be beneficial to Dietitians and other
      clinicians who wish to follow a more family-based approach and may present new
      avenues for effective treatment. In our tertiary care pediatric obesity clinic,
      we routinely involve multiple family members throughout the treatment process.
      Here we discuss our experiences and introduce Bowen's Family Systems Theory as a
      model for translating family therapy principles into nutrition-focused treatment
      settings.

PMID- 24729832
TI  - Meeting the Housing and Care Needs of Older Homeless Adults: A Permanent
      Supportive Housing Program Targeting Homeless Elders.
AB  - The homeless population is aging faster than the general population in the United
      States. As this vulnerable population continues to age, addressing complex care
      and housing needs will become increasingly important. This article reviews the
      often-overlooked issue of homelessness among older adults, including their poor
      health status and unique care needs, the factors that contribute to homelessness
      in this population, and the costs of homelessness to the U.S. health care system.
      Permanent supportive housing programs are presented as a potential solution to
      elder homelessness, and Hearth, an outreach and permanent supportive housing
      model in Boston, is described. Finally, specific policy changes are presented
      that could promote access to housing among the growing older homeless population.

PMID- 24729833
TI  - Molecular imaging of macrophage enzyme activity in cardiac inflammation.
AB  - Molecular imaging is highly advantageous as various insidious inflammatory events
      can be imaged in a serial and quantitative fashion. Combined with the
      conventional imaging modalities like computed tomography (CT), magnetic resonance
      (MR) and nuclear imaging, it helps us resolve the extent of ongoing pathology,
      quantify inflammation and predict outcome. Macrophages are increasingly gaining
      importance as an imaging biomarker in inflammatory cardiovascular diseases.
      Macrophages, recruited to the site of injury, internalize necrotic or foreign
      material. Along with phagocytosis, activated macrophages release proteolytic
      enzymes like matrix metalloproteinases (MMPs) and cathepsins into the
      extracellular environment. Pro-inflammatory monocytes and macrophages also induce
      tissue oxidative damage through the inflammatory enzyme myeloperoxidase (MPO). In
      this review we will highlight recent advances in molecular macrophage imaging.
      Particular stress will be given to macrophage functional and enzymatic activity
      imaging which targets phagocytosis, proteolysis and myeloperoxidase activity
      imaging.

PMID- 24729834
TI  - Trisubstituted Sulfonamides: a New Chemotype for Development of Potent and
      Selective CB2 Receptor Inverse Agonists.
AB  - An extensive exploration of the SAR of a trisubstituted sulfonamides series led
      to the identification of 39, which is a potent and selective CB2 receptor inverse
      agonist (CB2Ki = 5.4 nM, and CB1Ki = 500 nM). The functional properties measured
      by cAMP assays indicated that the selected compounds were CB2 inverse agonists
      with high potency values (34, EC50 = 8.2 nM, and 39, EC50 = 2.5 nM). Furthermore,
      an osteoclastogenesis bioassay indicated that trisubstituted sulfonamide
      compounds showed great inhibition of osteoclast formation.

PMID- 24729835
TI  - Recovery from stress - a cell cycle perspective.
AB  - We develop a Boolean model to explore the dynamical behaviour of budding yeast in
      response to osmotic and pheromone stress. Our model predicts that osmotic stress
      halts the cell cycle progression in either of four possible arrest points. The
      state of the cell at the onset of the stress dictates which arrest point is
      finally reached. According to our study and consistent with biological data,
      these cells can return to the cell cycle after removal of the stress. Moreover,
      the Boolean model illustrates how osmotic stress alters the state transitions of
      the cell. Furthermore, we investigate the influence of a particular pheromone
      based method for the synchronisation of the cell cycles in a population of cells.
      We show this technique is not a suitable method to study one of the arrest points
      under osmotic stress. Finally, we discuss how an osmotic stress can cause some of
      the so called frozen cells to divide. In this case the stress can move these
      cells to the cell cycle trajectory, such that they will replicate again.

PMID- 24729836
TI  - New photon-counting detectors for single-molecule fluorescence spectroscopy and
      imaging.
AB  - Solution-based single-molecule fluorescence spectroscopy is a powerful new
      experimental approach with applications in all fields of natural sciences. Two
      typical geometries can be used for these experiments: point-like and widefield
      excitation and detection. In point-like geometries, the basic concept is to
      excite and collect light from a very small volume (typically femtoliter) and work
      in a concentration regime resulting in rare burst-like events corresponding to
      the transit of a single-molecule. Those events are accumulated over time to
      achieve proper statistical accuracy. Therefore the advantage of extreme
      sensitivity is somewhat counterbalanced by a very long acquisition time. One way
      to speed up data acquisition is parallelization. Here we will discuss a general
      approach to address this issue, using a multispot excitation and detection
      geometry that can accommodate different types of novel highly-parallel detector
      arrays. We will illustrate the potential of this approach with fluorescence
      correlation spectroscopy (FCS) and single-molecule fluorescence measurements. In
      widefield geometries, the same issues of background reduction and single-molecule
      concentration apply, but the duration of the experiment is fixed by the time
      scale of the process studied and the survival time of the fluorescent probe.
      Temporal resolution on the other hand, is limited by signal-to-noise and/or
      detector resolution, which calls for new detector concepts. We will briefly
      present our recent results in this domain.

PMID- 24729837
TI  - Appropriate tube size selection based on radiological images.

PMID- 24729838
TI  - Attention to postoperative pain control in children.
AB  - Even with the rapid development of pediatric postoperative pain management,
      pediatric patients have remained undertreated for postoperative pain because of
      difficulty in pain assessment and concerns regarding side effects of opioid
      analgesics. Although there are no perfect pain assessment techniques and no
      absolutely safe analgesics, proper monitoring and an individualized analgesic
      plan after due consideration of age, operative procedures, and underlying
      illness, using multimodal analgesics may improve the quality of pain control in
      children. 

PMID- 24729839
TI  - The comparison of the lengths and diameters of main bronchi measured from two
      dimensional and three-dimensional images in the same patients.
AB  - BACKGROUND: Recently, multi-planar reconstruction of the three-dimensional (3D)
      spiral chest CT scan has demonstrated superiority in the evaluation of the
      tracheobronchial tree. The goal of this study was to measure the lengths of the
      right and left main bronchi and their anteroposterior (AP) and transverse (TR)
      diameters using the 3D and two-dimensional (2D) images in the same adult
      respectively, and to evaluate the degree of correlation between them. METHODS: We
      measured the lengths of the right and left main bronchi from the carina to the
      first of their branches and the AP and TR diameters at the mid-portion of the
      right main bronchus and 2 cm below the carina in the left main bronchus. We
      determined the size of the left-sided double-lumen tube (DLT) based on the
      measured AP diameter of the left main bronchus from the 3D and 2D images,
      respectively. RESULTS: There was moderate correlation between the lengths of both
      main bronchi obtained from the 3D images and the 2D images, and between the AP
      diameter of the left main bronchus obtained from the 3D images and the 2D images.
      Same sized DLTs were estimated in 69% of the men and 34% of the women.
      CONCLUSIONS: The lengths of the right and left main bronchi and their AP and TR
      diameters obtained from 3D images were not strongly correlated with those from 2D
      images. Therefore, a further study is needed to verify the superiority of 3D
      images in selecting the appropriate size of left-sided DLT.

PMID- 24729840
TI  - A method for optimal depth of the nasopharyngeal temperature probe: the philtrum
      to tragus distance.
AB  - BACKGROUND: The nasopharyngeal temperature probe should be placed in the upper
      nasopharynx to reflect accurate core temperature. However, there have been no
      studies conducted to predict parameters for the optimal depth of the
      nasopharyngeal temperature probe. The purpose of this study was to examine the
      correlation between the optimal depth to the upper nasopharynx and the distance
      from the philtrum to the tragus and height. METHODS: Two hundred patients (100
      females and 100 males) were enrolled in the study. The distance from the philtrum
      to the tragus along the facial curvature was measured, and the optimal depth from
      the nostril to the upper nasopharynx was evaluated using nasendoscopy. The
      relationships between the optimal depth to the upper nasopharynx and the distance
      from the philtrum to the tragus and height were examined. RESULTS: The distances
      from the philtrum to the tragus were 14.4 +/- 0.5 cm in females and 15.1 +/- 0.6
      cm in males (P < 0.01). The depths from the nostril to the upper nasopharynx were
      9.4 +/- 0.6 cm in females and 10.0 +/- 0.5 cm in males (P < 0.01). The
      correlation coefficients between the depth from the nostril to the upper
      nasopharynx and the distance to the tragus from the philtrum were 0.43 in females
      and 0.41 in males (P < 0.01). However, there were very weak correlations and no
      correlations between height and the depth from the nostril to the upper
      nasopharynx in females and males, respectively. CONCLUSIONS: The depth from the
      nostril to the upper nasopharynx is correlated weakly with the distance from the
      philtrum to the tragus. Although the distance from the philtrum to the tragus is
      not a good predicting parameter for the optimal depth of nasopharyngeal
      temperature probe placement, subtraction of 5 cm from the distance is helpful to
      estimate the optimal depth of the nasopharyngeal temperature probe.

PMID- 24729842
TI  - Reduction in labor pain by intrathecal midazolam as an adjunct to sufentanil.
AB  - BACKGROUND: Anesthesia today has strived to decrease labor pain in a tolerable
      and controllable fashion. Intrathecal midazolam has been introduced as an adjunct
      to analgesics. The study was planned to assess the efficacy, safety and duration
      of analgesia produced by intrathecal midazolam adjunct to sufentanil in
      decreasing labor pain. METHODS: In a randomized clinical trial 80 parturient
      included in the study. The two groups were matched for age, cervical dilation,
      gravid, gestational age, and other demographic characteristics. Combination of
      sufentanil and midazolam administered intrathecally to experimental group and
      compared to sufentanil group. Time to reach maximum block, and pain score was
      measured and recorded. RESULTS: Groups were matched for age and weight and other
      demographic characteristic. No significant adverse effect was seen in both groups
      including decrease in Apgar score. Duration of analgesia was 92.0 +/- 12.7 in
      sufentanil group and 185.2 +/- 15.2 minutes in midazolam and sufentanil group
      which was significantly different (P = 0.002). Numeric rating scale score was
      significantly lower in midazolam group compare to sufentanil group at 120 min (P
      = 0.01), 150 min (P = 0.0014), and 180 min (P = 0.001). CONCLUSIONS: Intrathecal
      midazolam as an adjunct to opioid could significantly enhance analgesia in labor
      pain with no significant adverse effect. Intrathecal injection of midazolam is an
      appropriate alternative to parenteral or epidural analgesia in small hospital
      settings.

PMID- 24729841
TI  - Alteration of the QT variability index in end-stage liver disease.
AB  - BACKGROUND: A prolonged QT interval can lead to malignant ventricular arrhythmias
      and sudden cardiac death, and has frequently been found in end-stage liver
      disease (ESLD). However, myocardial repolarization lability has not yet been
      fully investigated. We evaluated the QT variability index (QTVI), a marker of
      temporal inhomogeneity in ventricular repolarization and an abnormality
      associated with re-entrant malignant ventricular arrhythmias. We determined
      whether QTVI is affected by the head-up tilt test in ESLD. METHODS: We assessed
      36 ESLD patients and 12 control subjects without overt heart disease before and
      after the 70-degree head-up tilt test. The electrocardiography signal (lead II)
      was recorded on a computer with an analog-to-digital converter. The RR interval
      (RRI) and QT interval were measured after recording 5 min of the digitized
      electrocardiography. Then, the QT intervals were corrected with Bazett's formula
      (QTc). QTVI was calculated through the following formula: QTVI = log10
      [(QTv/QTm2)/(RRIv/RRIm2)], QTv/RRIv: variance of QTI/RRI, QTm/RRIm: mean of QT
      interval/RRI. RESULTS: Cirrhotic patients exhibited an elevated QTVI. In
      particular, Child class C patients had a significantly increased QTVI compared to
      Child class A patients and the control subjects in the supine position. However,
      the head-up tilt test did not cause a significant difference in QTVI in relation
      to the severity of ESLD. CONCLUSIONS: Myocardial repolarization lability was
      significantly altered in end-stage liver disease. Our data suggest that the
      severity of ESLD is associated with the degree of the alteration in the QT
      variability index.

PMID- 24729843
TI  - Antiemetic effect of propofol administered at the end of surgery in laparoscopic
      assisted vaginal hysterectomy.
AB  - BACKGROUND: Postoperative nausea and vomiting (PONV) commonly occur after general
      anesthesia, especially in women. In this study, we evaluated the antiemetic
      efficacy of propofol administered at the end of surgery in highly susceptible
      patients undergoing a laparoscopy-assisted vaginal hysterectomy. METHODS: A total
      of 107 women undergoing a laparoscopy-assisted vaginal hysterectomy under general
      anesthesia were enrolled for this prospective, double-blind, randomized study.
      Fifteen minutes before the end of surgery, all patients received 50 ug fentanyl
      and 1 of following 3 doses; 0.5 mg/kg of propofol (propofol 0.5 group), 1 mg/kg
      of propofol (propofol 1.0 group), and normal saline (control group). All patients
      received intravenous patient-controlled analgesia (PCA). Emergence time, a visual
      analog scale for pain and nausea, duration of postanesthesia care unit (PACU)
      stay, and frequency of antiemetic use were recorded at 0-2, 2-24, and 24-48 hours
      postoperatively. RESULTS: The incidence of nausea significantly lower in the
      propofol 0.5 and propofol 1.0 groups than in the control group (12.1 vs 14.7 vs
      40%). During the first postoperative 2 hours, antiemetics were less frequently
      administered in the propofol 0.5 and propofol 1.0 groups than in the control
      group (3.0 vs 5.9 vs 22.5%). Emergence time was slightly longer in the propofol
      0.5 and propofol 1.0 groups than in the control group, but there was no
      significant difference in PACU stay time was observed between the 3 groups.
      CONCLUSIONS: The results of this study suggest that low-dose propofol
      administration at the end of surgery may effectively reduce the incidence of PONV
      within 2 hours postoperatively in highly susceptible women undergoing a
      laparoscopiy-assisted vaginal hysterectomy and receiving opioid-based PCA.

PMID- 24729844
TI  - Postoperative nausea and vomiting after total thyroidectomy: sevoflurane combined
      with prophylactic ramosetron vs. propofol-based total intravenous anesthesia.
AB  - BACKGROUND: The frequent and distressing adverse events (AEs) of postoperative
      nausea and vomiting (PONV) are of major concern in 63-84% of adult patients
      undergoing thyroidectomy. We conducted this prospective study to compare two
      prophylactic strategies; sevoflurane combined with ramosetron and propofol-based
      total intravenous anesthesia in a homogenous group of non-smoking women
      undergoing total thyroidectomy. METHODS: In the current prospective study, we
      enrolled a consecutive series of 64 female patients aged between 20 and 65 years
      with an American Society of Anesthesiologists physical status of I or II who were
      scheduled to undergo elective total thyroidectomy under general anesthesia.
      Patients were randomized to either the SR (sevoflurane and remifentanil) group or
      the TIVA group. We evaluated the incidence and severity of PONV, the use of
      rescue anti-emetics and the severity of pain during the first 24 h after surgery.
      RESULTS: There were no significant differences in the proportion of the patients
      with a complete response and the Rhodes index, including the occurrence score,
      distress score and experience score, between the two groups. In addition, there
      were no significant differences in the proportion of the patients who were in
      need of rescue anti-emetics or analgesics and the VAS scores between the two
      groups. CONCLUSIONS: In conclusion, TIVA and ramosetron prophylaxis reduced the
      expected incidence of PONV in women undergoing total thyroidectomy. In addition,
      there was no significant difference in the efficacy during the first 24 h
      postoperatively between the two prophylactic regimens.

PMID- 24729846
TI  - G protein-coupled receptor, family C, group 5 (GPRC5B) downregulation in spinal
      cord neurons is involved in neuropathic pain.
AB  - BACKGROUND: G protein-coupled receptor, family C, group 5 (GPRC5B), a retinoic
      acid-inducible orphan G-protein-coupled receptor (GPCR), is a member of the group
      C metabotropic glutamate receptor family proteins presumably related in non
      canonical Wnt signaling. In this study, we investigated altered GPRC5B expression
      in the dorsal horn of the spinal cord after spinal nerve injury and its
      involvement in the development of neuropathic pain. METHODS: After induction of
      anesthesia by intraperitoneal injection of pentobarbital (35 mg /kg), the left L5
      spinal nerve at the level of 2 mm distal to the L5 DRG was tightly ligated with
      silk and cut just distal to the ligature. Seven days after nerve injury, animals
      were perfused with 4% paraformaldehyde, and the spinal cords were extracted and
      post-fixed at 4C overnight. To identify the expression of GPRC5B and analyze the
      involvement of GPRC5B in neuropathic pain, immunofluorescence was performed using
      several markers for neurons and glial cells in spinal cord tissue. RESULTS: After
      L5 spinal nerve ligation (SNL), the expression of GPRC5B was decreased in the
      ipsilateral part, as compared to the contralateral part, of the spinal dorsal
      horn. SNL induced the downregulation of GPRC5B in NeuN-positive neurons in the
      spinal dorsal horn. However, CNPase-positive oligodendrocytes, OX42-positive
      microglia, and GFAP-positive astrocytes were not immunolabeled with GPRC5B
      antibody in the spinal dorsal horn. CONCLUSIONS: These results imply that L5 SNL
      induced GPRC5B downregulation may affect microglial activation in the spinal
      dorsal horn and be involved in neuropathic pain.

PMID- 24729845
TI  - Comparison of effects of intraoperative esmolol and ketamine infusion on acute
      postoperative pain after remifentanil-based anesthesia in patients undergoing
      laparoscopic cholecystectomy.
AB  - BACKGROUND: Remifentanil is a short-acting drug with a rapid onset that is useful
      in general anesthesia. Recently, however, it has been suggested that the use of
      opioids during surgery may cause opioid-induced hyperalgesia (OIH). Researchers
      have recently reported that esmolol, an ultra-short-acing beta1 receptor
      antagonist, reduces the postoperative requirement for morphine and provides more
      effective analgesia than the administration of remifentanil and ketamine. Hence,
      this study was conducted to determine whether esmolol reduces early postoperative
      pain in patients who are continuously infused with remifentanil for anesthesia
      during laparoscopic cholecystectomy. METHODS: Sixty patients scheduled to undergo
      laparoscopic cholecystectomy were randomly divided into three groups. Anesthesia
      was maintained with sevoflurane and 4 ng/ml (target-controlled infusion) of
      remifentanil in all patients. Esmolol (0.5 mg/kg) was injected and followed with
      a continuous dosage of 10 ug/kg/min in the esmolol group (n = 20). Ketamine (0.3
      mg/kg) was injected and followed with a continuous dosage of 3 ug/kg/min in the
      ketamine group (n = 20), while the control group was injected and infused with an
      equal amount of normal saline. Postoperative pain score (visual analog scale
      [VAS]) and analgesic requirements were compared for the first 6 hours of the
      postoperative period. RESULTS: The pain score (VAS) and fentanyl requirement for
      15 minutes after surgery were lower in the esmolol and ketamine groups compared
      with the control group (P < 0.05). There were no differences between the esmolol
      and ketamine groups. CONCLUSIONS: Intraoperative esmolol infusion during
      laparoscopic cholecystectomy reduced opioid requirement and pain score (VAS)
      during the early postoperative period after remifentanil-based anesthesia.

PMID- 24729847
TI  - Endotracheal tube intubation with the aid of a laryngeal mask airway, a
      fiberoptic bronchoscope, and a tube exchanger in a difficult airway patient: a
      case report.
AB  - A 28-year-old male patient with occipito-atlanto-axial instability underwent a
      cervical fusion with posterior technique. Post-operatively, the endotracheal tube
      (ETT) was removed, and the patient was transferred to the intensive care unit.
      After transfer, an upper airway obstruction developed and reintubations with a
      laryngoscope were attempted but failed. We inserted a #4 proseal laryngeal mask
      airway (LMA) and passed a 5.0 mm ETT through the LMA with the aid of a fiberoptic
      bronchoscope. We passed a tube exchanger through the 5.0 mm ETT and exchanged it
      with a 7.5 mm ETT. This method may be a useful alternative for difficult tracheal
      intubations. 

PMID- 24729848
TI  - Epidural hematoma after thoracic epidural analgesia in a patient treated with
      ketorolac, mefenamic acid, and naftazone: a case report.
AB  - A 26-year-old male undergoing thoracotomy and bleeding control received a
      preoperative thoracic epidural for postoperative analgesia. On the fifth
      postoperative day, paralysis of both lower limbs occurred and urgent magnetic
      resonance imaging showed massive anterior epidural hematoma. During laminectomy
      and decompression, platelet dysfunction was diagnosed and preoperative non
      steroidal anti-inflammatory drugs medications were supposed to the cause of
      platelet dysfunction. After infusion of ten units of platelet concentrate,
      coagulopathy was improved. We should be more careful to drugs with antiplatelet
      effect when using regional analgesia. 

PMID- 24729849
TI  - Conversion of supraventricular arrhythmia to normal rhythm by propofol and
      remifentanil: three cases report.
AB  - We experienced conversion of supraventricular arrhythmia to normal sinus rhythm
      in three patients during general anesthesia using propofol and remifentanil. This
      may be related to direct inhibition of the cardiac conduction system or
      activation of the parasympathetic system. The literature review suggests that
      propofol and remifentanil have antiarrhythmic potential, reverting
      supraventricular arrhythmia during anesthesia. 

PMID- 24729850
TI  - Point-of-care monitoring of perioperative intraocular pressure using portable
      tonometry in a patient with Posner-Schlossman syndrome: a case report.
AB  - A 56-year-old man with a rotator cuff injury, scheduled for arthroscopic
      reconstruction surgery, had a history of recurrent symptoms of eyeball pain and
      blurred vision for several years. After close examination, he was diagnosed with
      Posner-Schlossman syndrome. Three weeks before the scheduled surgery, his
      intraocular pressure (IOP) increased (> 30 mmHg) and he became extremely anxious
      about the surgery. We monitored his IOP intraoperatively and successfully
      completed general anesthesia without any sequelae. As Posner-Schlossman syndrome
      can present with severe complications that may lead to postoperative visual loss,
      intraoperative monitoring of intraocular monitoring and careful anesthetic
      management are crucial to protect vision. 

PMID- 24729851
TI  - Anesthetic management of laparoscopic pheochromocytoma excision in a patient with
      a Fontan circulation: a case report.
AB  - An 18-year-old male with a Fontan circulation underwent excision of a
      pheochromocytoma after conversion from laparoscopic surgery. The pneumoperitoneum
      established for laparoscopic surgery may have adverse effects on the Fontan
      circulation, because it increases the intra-abdominal pressure (IAP), intra
      thoracic pressure, pulmonary vascular resistance, and systemic vascular
      resistance (SVR), and decreases cardiac preload and cardiac output. Meticulous
      monitoring is also required during carbon dioxide exsufflation, because a rapid
      decrease in IAP can provoke hemodynamic deterioration by decreasing venous return
      and SVR. Furthermore, catecholamines released by the pheochromocytoma can worsen
      the hemodynamic status of Fontan circulation during surgery. Therefore,
      sophisticated intraoperative anesthetic care is required during laparoscopic
      pheochromocytoma excision in patients with a Fontan circulation. 

PMID- 24729852
TI  - Perioperative hypothermia during surgery: is warming humidification a complete
      solution?

PMID- 24729853
TI  - Potential association between prediabetic conditions and gingival and/or
      periodontal inflammation.
AB  - AIMS/INTRODUCTION: Prediabetic conditions, which include impaired fasting glucose
      (IFG) and impaired glucose tolerance (IGT), might be associated with chronic
      gingival and/or periodontal inflammation. However, the occurrence of this oral
      inflammation in prediabetic conditions is poorly understood. The present study
      aimed to assess the association between prediabetes and gingival and/or
      periodontal inflammation. MATERIALS AND METHODS: A total of 94 Puerto Rican men
      and women aged 40-65 years, who were residents of San Juan, Puerto Rico, and free
      of diabetes, were included in the study. All participants had at least one tooth
      site with clinical attachment loss >=3 mm. Fasting and 2-h plasma glucose were
      collected. Gingival/periodontal inflammation was assessed by bleeding on gentle
      probing of the sulcus at six sites per tooth. RESULTS: Participants with the
      percentage of teeth with bleeding on probing (BOP) equal to or greater than the
      median were compared with those with the percentage of teeth with BOP less than
      median. Participants with high BOP tended to present higher IFG (odds ratio [OR]
      5.5, 95% confidence interval [CI] 1.2-25.3) and/or prediabetic condition (OR 3.6,
      95% CI 1.0-13.2) than those with a low percentage of BOP, adjusting for age, sex,
      smoking, alcohol consumption, waist circumference and number of missing teeth.
      Using the continuous form of the outcome, the corresponding adjusted least
      squares means of percentage of BOP were 26.8 (standard error of the mean [SEM]
      2.3) and 43.8 (SEM 6.0) in normal and IFG, respectively (P = 0.01), and 27.0 (SEM
      2.4) and 39.0 (SEM 5.3) among healthy and prediabetic individuals, respectively
      (P = 0.05). CONCLUSION: IFG and/or prediabetes are strongly associated with BOP,
      a marker of chronic gingival/periodontal inflammation.

PMID- 24729854
TI  - Radical Reactivity of the Fe(III)/(II) Tetramesitylporphyrin Couple: Hydrogen
      Atom Transfer, Oxyl Radical Dissociation, and Catalytic Disproportionation of a
      Hydroxylamine.
AB  - The chemistry of low-valent iron porphyrin complexes with oxyl radical reagents
      has been explored. (Meso-tetramesityl porphyrinato) iron(III) hydroxide,
      (TMP)FeIII(OH) reacts with the hydroxylamine TEMPO-H (1-hydroxy-2,2,6,6
      tetramethylpiperdine) to yield the ferrous porphyrin, (TMP)FeII, together with
      H2O and TEMPO. This reaction has a second order rate constant k1 = 76 +/- 5 M-1 1
      s-1 and likely occurs by concerted e-/H+ transfer. Hydrazines PhNHNHPh and
      PhNHNH2 similarly yield (TMP)FeII. A subsequent reaction between TEMPO (2,2,6,6
      tetramethylpiperdinyl radical) and (TMP)FeII is observed to reversibly form the
      TEMPO-ligated ferric porphyrin, (TMP)FeIII(TEMPO). A combination of 1H NMR and
      optical spectroscopies were used to determine the thermodynamic parameters for
      TEMPO binding: K4 (25 degrees C) = 535 +/- 20 M-1, DeltaH degrees 4 = -7.0 +/-
      1.5 kcal mol-1, DeltaS degrees 4= -11 +/- 5 cal mol-1 K-1, DeltaG?4(235K) = 21.3
      +/- 0.5 kcal mol-1, DeltaG?-4(235K) = 16.9 +/- 0.5 kcal mol-1. The Fe-O bond is
      remarkably weak. The stable phenoxyl radical 2,4,6- t Bu3C6H2O* (ArO*) forms a
      stronger bond to (TMP)FeII to irreversibly make a similar FeIII(OR) complex. Both
      (TMP)FeII and (TMP)FeIII(OH) are catalysts for the disproportionation of excess
      TEMPO-H to TEMPO and TEMP-H (2,2,6,6-tetramethylpiperdine). The lack of
      reactivity between (TMP)FeII and the alkylated TEMPO-H analogue, TEMPO-CH3,
      suggests that the disproportionation involves a hydrogen atom transfer step.
      These results highlight the importance and versatility of the heme FeIII/II
      couple that is often overshadowed by its higher-valent counterparts.

PMID- 24729856
TI  - Putting medical risks into perspective.

PMID- 24729855
TI  - Synthesis and Properties of Fully-Conjugated Indacenedithiophenes.
AB  - The synthesis and characterization of four fully-conjugated indacenedithiophenes
      (IDTs) are disclosed. In contrast to anthradithiophenes, regioselective synthesis
      of both syn and anti isomers is readily achieved. Thiophene fusion imparts
      increased paratropic character on the central indacene core as predicted by DFT
      calculations and confirmed by 1H NMR spectroscopy. IDTs exhibit red-shifted
      absorbance maxima with respect to their all-carbon analogues and undergo two
      electron reduction and one-electron oxidation.

PMID- 24715953
TI  - A novel variable delay Go/No-Go task to study attention, motivation and working
      memory in the head-fixed rodent.
AB  - In order to parse the causal elements underlying complex behaviors and decision
      making processes, appropriate behavioral methods must be developed and used in
      concurrence with molecular, pharmacological, and electrophysiological approaches.
      Presented is a protocol for a novel Go/No-Go behavioral paradigm to study the
      brain attention and motivation/reward circuitry in awake, head-restrained
      rodents. This experimental setup allows: (1) Pharmacological and viral
      manipulation of various brain regions via targeted guide cannula; (2) Optogenetic
      cell-type specific activation and silencing with simultaneous
      electrophysiological recording and; (3) Repeated electrophysiological single and
      multiple unit recordings during ongoing behavior. The task consists of three
      components. The subject first makes an observing response by initiating a trial
      by lever pressing in response to distinctive Go or No-Go tones.  Then, after a
      variable delay period, the subject is presented with a challenge period cued by
      white noise during which they must respond with a lever press for the Go
      condition or withhold from lever pressing for the duration of the cue in the No
      Go condition. After correctly responding during the challenge period (Challenge)
      and a brief delay, a final reward tone of the same frequency as the initiation
      tone is presented and sucrose reward delivery is available and contingent upon
      lever pressing. Here, we provide a novel procedure and validating data set that
      allows researchers to study and manipulate components of behavior such as
      attention, motivation, impulsivity, and reward-related working memory during an
      ongoing operant behavioral task while limiting interference from non task-related
      behaviors. 

PMID- 24715952
TI  - Use of botulinum toxin in musculoskeletal pain.
AB  - Chronic musculoskeletal pain is a common cause of chronic pain, which is
      associated with a total cost of $635 billion per year in the U.S. Emerging
      evidence suggests an anti-nociceptive action of botulinum toxin, independent of
      its muscle paralyzing action. This review provides a summary of data from both
      non-randomized and randomized clinical studies of botulinum toxin in back pain
      and various osteoarticular conditions, including osteoarthritis, tennis elbow,
      low back pain and hand pain. Three randomized controlled trials (RCTs) of small
      sizes provide evidence of short-term efficacy of a single intra-articular
      injection of 100 units of botulinum toxin A (BoNT/A) for the relief of pain and
      the improvement of both function and quality of life in patients with chronic
      joint pain due to arthritis. Three RCTs studied intramuscular BoNT/A for tennis
      elbow with one showing a significant improvement in pain relief compared with
      placebo, another one showing no difference from placebo, and the third finding
      that pain and function improvement with BoNT/A injection were similar to those
      obtained with surgical release. One RCT of intramuscular BoNT/A for low back pain
      found improvement in pain and function compared to placebo. Single RCTs using
      local injections of BoNT in patients with either temporomandibular joint (TMJ)
      pain or plantar fasciitis found superior efficacy compared to placebo. One RCT of
      intramuscular BoNT/B in patients with hand pain and carpal tunnel syndrome found
      improvement in pain in both BoNT/B and placebo groups, but no significant
      difference between groups. Most evidence is based on small studies, but the use
      of BoNT is supported by a single, and sometimes up to three, RCTs for several
      chronic musculoskeletal pain conditions. This indicates that botulinum toxin may
      be a promising potential new treatment for chronic refractory musculoskeletal
      pain. Well-designed large clinical trials are needed. 

PMID- 24715954
TI  - Co-implanting orthotopic tissue creates stroma microenvironment enhancing growth
      and angiogenesis of multiple tumors.
AB  - Tumor models are needed to study cancer. Noninvasive imaging of tumors under
      native conditions in vivo is critical but challenging. Intravital microscopy
      (IVM) of subcutaneous tumors provides dynamic, continuous, long-term imaging at
      high resolution. Although popular, subcutaneous tumor models are often criticized
      for being ectopic and lacking orthotopic tissue microenvironments critical for
      proper development. Similar IVM of orthotopic and especially spontaneous tumors
      is seldom possible. Here, we generate and characterize tumor models in mice for
      breast, lung, prostate and ovarian cancer by co-engrafting tumor spheroids with
      orthotopic tissue in dorsal skin window chambers for IVM. We use tumor cells and
      tissue, both genetically engineered to express distinct fluorescent proteins, in
      order to distinguish neoplastic cells from engrafted tissue. IVM of this new, two
      colored model reveals classic tumor morphology with red tumor cell nests
      surrounded by green stromal elements. The co-implanted tissue forms the
      supportive stroma and vasculature of these tumors. Tumor growth and angiogenesis
      are more robust when tumor cells are co-implanted with orthotopic tissue versus
      other tissues, or in the skin alone. The orthotopic tissue promotes tumor cell
      mitosis over apoptosis. With time, tumor cells can adapt to new environments and
      ultimately even grow better in the non-orthotopic tissue over the original
      orthotopic tissue. These models offer a significant advance by recreating an
      orthotopic microenvironment in an ectopic location that is still easy to image by
      IVM. These "ectopic-orthotopic" models provide an exceptional way to study tumor
      and stroma cells in cancer, and directly show the critical importance of
      microenvironment in the development of multiple tumors. 

PMID- 24715958
TI  - The Human dsRNA binding protein PACT is unable to functionally substitute for the
      Drosophila dsRNA binding protein R2D2.
AB  - The dsRNA binding protein (dsRBP) PACT was first described as an activator of the
      dsRNA dependent protein kinase PKR in response to stress signals.  Additionally,
      it has been identified as a component of the small RNA processing pathway.  A
      role for PACT in this pathway represents an important interplay between two modes
      of post-transcriptional gene regulation.  The function of PACT in this context is
      poorly understood.  Thus, additional approaches are required to clarify the
      mechanism by which PACT functions.  In this study, the genetic utility of 
      Drosophila melanogaster was employed to identify dsRNA-binding proteins that are
      functionally orthologous to PACT.  Transgenic  Drosophila expressing human PACT
      were generated to determine whether PACT is capable of functionally substituting
      for the  Drosophila dsRBP R2D2, which has a well-defined role in small RNA
      biogenesis.  Results presented here indicate that PACT is unable to substitute
      for R2D2 at the whole organism level. 

PMID- 24715967
TI  - Thermoregulation strategies in ants in comparison to other social insects, with a
      focus on red wood ants ( Formica rufa group).
AB  - Temperature influences every aspect of ant biology, especially metabolic rate,
      growth and development. Maintenance of high inner nest temperature increases the
      rate of sexual brood development and thereby increases the colony fitness. Insect
      societies can achieve better thermoregulation than solitary insects due to the
      former's ability to build large and elaborated nests and display complex
      behaviour. In ants and termites the upper part of the nest, the mound, often
      works as a solar collector and can also have an efficient ventilation system. Two
      thermoregulatory strategies could be applied. Firstly the ants use an increased
      thermal gradient available in the mound for brood relocation. Nurse workers move
      the brood according to the thermal gradients to ensure the ideal conditions for
      development. A precise perception of temperature and evolution of temperature
      preferences are needed to make the correct choices. A second thermoregulatory
      strategy used by mound nesting ants is keeping a high temperature inside large
      nests. The unique thermal and insulation properties of the nest material help to
      maintain stable conditions, which is the case of the Wood ant genus Formica. Ants
      can regulate thermal loss by moving nest aggregation and alternating nest
      ventilation. Metabolic heat produced by ant workers or associated micro organisms
      is an important additional source of heat which helps to maintain thermal
      homeostasis in the nest. 

PMID- 24715962
TI  - Monitoring ferumoxide-labelled neural progenitor cells and lesion evolution by
      magnetic resonance imaging in a model of cell transplantation in cerebral
      ischaemia.
AB  - Efficacy of neural stem/progenitor cell (NPC) therapies after cerebral ischaemia
      could be better evaluated by monitoring in vivo migration and distribution of
      cells post-engraftment in parallel with analysis of lesion volume and functional
      recovery. Magnetic resonance imaging (MRI) is ideally placed to achieve this, but
      still poses several challenges. We show that combining the ferumoxide MRI
      contrast agent Endorem with protamine sulphate (FePro) improves iron oxide uptake
      in cells compared to Endorem alone and is non-toxic. Hence FePro complex is a
      better contrast agent than Endorem for monitoring NPCs. FePro complex-labelled
      NPCs proliferated and differentiated normally in vitro, and upon grafting into
      the brain 48 hours post-ischaemia they were detected in vivo by MRI. Imaging over
      four weeks showed the development of a confounding endogenous hypointense
      contrast evolution at later timepoints within the lesioned tissue. This was at
      least partly due to accumulation within the lesion of macrophages and endogenous
      iron. Neither significant NPC migration, assessed by MRI and histologically, nor
      a reduction in the ischaemic lesion volume was observed in NPC-grafted brains. 
      Crucially, while MRI provides reliable information on engrafted cell location
      early after an ischaemic insult, pathophysiological changes to ischaemic lesions
      can interfere with cellular imaging at later timepoints. 

PMID- 24715968
TI  - Rapid and inexpensive body fluid identification by RNA profiling-based multiplex
      High Resolution Melt (HRM) analysis.
AB  - Positive identification of the nature of biological material present on
      evidentiary items can be crucial for understanding the circumstances surrounding
      a crime. However, traditional protein-based methods do not permit the
      identification of all body fluids and tissues, and thus molecular based
      strategies for the conclusive identification of all forensically relevant
      biological fluids and tissues need to be developed. Messenger RNA (mRNA)
      profiling is an example of such a molecular-based approach. Current mRNA body
      fluid identification assays involve capillary electrophoresis (CE) or
      quantitative RT-PCR (qRT-PCR) platforms, each with its own limitations. Both
      platforms require the use of expensive fluorescently labeled primers or probes.
      CE-based assays require separate amplification and detection steps thus
      increasing the analysis time. For qRT-PCR assays, only 3-4 markers can be
      included in a single reaction since each requires a different fluorescent dye. To
      simplify mRNA profiling assays, and reduce the time and cost of analysis, we have
      developed single- and multiplex body fluid High Resolution Melt (HRM) assays for
      the identification of common forensically relevant biological fluids and tissues.
      The incorporated biomarkers include IL19 (vaginal secretions), IL1F7 (skin),
      ALAS2 (blood), MMP10 (menstrual blood), HTN3 (saliva) and TGM4 (semen).  The HRM
      assays require only unlabeled PCR primers and a single saturating intercalating
      fluorescent dye (Eva Green). Each body-fluid-specific marker can easily be
      identified by the presence of a distinct melt peak. Usually, HRM assays are used
      to detect variants or isoforms for a single gene target. However, we have
      uniquely developed duplex and triplex HRM assays to permit the simultaneous
      detection of multiple targets per reaction. Here we describe the development and
      initial performance evaluation of the developed HRM assays. The results
      demonstrate the potential use of HRM assays for rapid, and relatively
      inexpensive, screening of biological evidence. 

PMID- 24715971
TI  - Modeling enzootic raccoon rabies from land use patterns - Georgia (USA) 2006
      2010.
AB  - We analyzed how land-use patterns and changes in urbanization influence reported
      rabid raccoons in Georgia from 2006 - 2010.  Using Geographical Information
      Systems and rabies surveillance data, multivariate analysis was conducted on 15
      land-use variables that included natural topography, agricultural development,
      and urbanization to model positive raccoon rabies cases while controlling for
      potential raccoon submission bias associated with higher human population
      densities.  Low intensity residential development was positively associated with
      reported rabid raccoons while a negative association was found with evergreen
      forest.  Evergreen forests may offer a barrier effect where resources are low and
      raccoon populations are not supported.  Areas with pure stands of upland
      evergreen forest might be utilized in baiting strategies for oral rabies
      vaccination programs where fewer or no baits may be needed.  Their use as a
      barrier should be considered carefully in a cost-effective strategy for oral
      rabies vaccination (ORV) programs to contain the western spread of this important
      zoonotic disease. 

PMID- 24729865
TI  - Aqueous Ionic Liquids and Deep Eutectic Solvents for Cellulosic Biomass
      Pretreatment and Saccharification.
AB  - Ionic liquids (ILs) have proven effective solvents for pretreating
      lignocellulose, leading to the fast saccharification of cellulose and
      hemicellulose. However, the high current cost of most ILs remains a major barrier
      to commercializing this recent approach at a practical scale. As a strategic
      detour, aqueous solutions of ILs are also being explored as less costly
      alternatives to neat ILs for cellulose pretreatment. However, limited studies on
      a few select IL systems are known and there remains no systematic survey of
      various ILs, eluding an in-depth understanding of pretreatment mechanisms
      afforded by aqueous IL systems. As a step toward filling this gap, this study
      presents results for Avicel cellulose pretreatment by neat and aqueous solutions
      (1.0 and 2.0 M) of 20 different ILs and three deep eutectic solvents, correlating
      enzymatic hydrolysis rates of pretreated cellulose with various IL properties
      such as hydrogen-bond basicity, polarity, Hofmeister ranking, and hydrophobicity.
      The pretreatment efficiencies of neat ILs may be loosely correlated to the
      hydrogen-bond basicity of the constituent anion and IL polarity; however, the
      pretreatment efficacies for aqueous ILs are more complicated and cannot be simply
      related to any single IL property. Several aqueous IL systems have been
      identified as effective alternatives to neat ILs in lignocellulose pretreatment.
      In particular, this study reveals that aqueous solutions of 1-butyl-3
      methylimidazolium methanesulfonate ([BMIM][MeSO3]) are effective for pretreating
      switchgrass (Panicum virgatum), resulting in fast saccharification of both
      cellulose and hemicellulose. An integrated analysis afforded by X-ray
      diffraction, scanning electron microscopy, thermogravimetric analysis and
      cellulase adsorption isotherm of lignocellulose samples is further used to
      deliver a more complete view of the structural changes attending aqueous IL
      pretreatment.

PMID- 24729866
TI  - Glymes as Versatile Solvents for Chemical Reactions and Processes: from the
      Laboratory to Industry.
AB  - Glymes, also known as glycol diethers, are saturated non-cyclic polyethers
      containing no other functional groups. Most glymes are usually less volatile and
      less toxic than common laboratory organic solvents; in this context, they are
      more environmentally benign solvents. However, it is also important to point out
      that some glymes could cause long-term reproductive and developmental damages
      despite their low acute toxicities. Glymes have both hydrophilic and hydrophobic
      characters that common organic solvents are lack of. In addition, they are
      usually thermally and chemically stable, and can even form complexes with ions.
      Therefore, glymes are found in a broad range of laboratory applications including
      organic synthesis, electrochemistry, biocatalysis, materials, and Chemical Vapor
      Deposition (CVD), etc. In addition, glyme are used in numerous industrial
      applications, such as cleaning products, inks, adhesives and coatings, batteries
      and electronics, absorption refrigeration and heat pumps, as well as
      pharmaceutical formulations, etc. However, there is a lack of comprehensive and
      critical review on this attractive subject. This review aims to accomplish this
      task by providing an in-depth understanding of glymes' physicochemical
      properties, toxicity and major applications.

PMID- 24729867
TI  - 3D printed tricalcium phosphate scaffolds: Effect of SrO and MgO doping on in
      vivo osteogenesis in a rat distal femoral defect model.
AB  - The presence of interconnected macro pores is important in tissue engineering
      scaffolds for guided tissue regeneration. This study reports in vivo biological
      performance of interconnected macro porous tricalcium phosphate (TCP) scaffolds
      due to the addition of SrO and MgO as dopants in TCP. We have used direct three
      dimensional printing (3DP) technology for scaffold fabrication followed by
      microwave sintering. Mechanical strength was evaluated by scaffolds with 500 um,
      750 um, and 1000 um interconnected designed pore sizes. Maximum compressive
      strength of 12.01 +/- 1.56 MPa was achieved for 500 um interconnected designed
      pore size Sr-Mg doped scaffold. In vivo biological performance of the microwave
      sintered pure TCP and Sr-Mg doped TCP scaffolds was assessed by implanting 350 um
      designed interconnected macro porous scaffolds in rat distal femoral defect.
      Sintered pore size of these 3D printed scaffolds were 311 +/- 5.9 um and 245 +/-
      7.5 um for pure and SrO-MgO doped TCP scaffolds, respectively. These 3D printed
      scaffolds possessed multiscale porosity, i.e., 3D interconnected designed macro
      pores along with intrinsic micro pores. Histomorphology and histomorphometric
      analysis revealed a significant increase in osteoid like new bone formation, and
      accelerated mineralization inside SrO and MgO doped 3D printed TCP scaffolds as
      compared to pure TCP scaffolds. An increase in osteocalcin and type I collagen
      level was also observed in rat blood serum with SrO and MgO doped TCP scaffolds
      compared to pure TCP scaffolds. Our results show that these 3D printed SrO and
      MgO doped TCP scaffolds with multiscale porosity contributed to early healing
      through accelerated osteogenesis.

PMID- 24729868
TI  - One-pot Synthesis of Elastin-like Polypeptide Hydrogels with Grafted VEGF-Mimetic
      Peptides.
AB  - Immobilization of growth factors to polymeric matrices has been a common strategy
      in the design of tissue engineering scaffolds to promote tissue regeneration,
      which requires complex cell signaling events with the surrounding matrix.
      However, the use of large protein growth factors in polymeric scaffolds is often
      plagued by immunogenicity, short in vivo half-lives, and reduced bioactivity. To
      address these concerns, we develop a single-step, cell-compatible strategy to
      tether small, growth-factor-mimetic peptides into a protein-engineered hydrogel
      with tunable biomaterial properties. Specifically, we covalently immobilize the
      QK peptide, an angiogenic peptide mimicking the receptor-binding region of
      vascular endothelial growth factor (VEGF), within tunable elastin-like
      polypeptide (ELP) hydrogels that include a cell-adhesive RGD sequence. Using a
      cell-compatible, amine-reactive crosslinker, we conducted a one-pot synthesis to
      simultaneously encapsulate cells while precisely controlling the QK grafting
      density (10 nM - 100 MUM) in the ELP hydrogels without altering other material
      properties. Fluorescence analysis of fluor-labeled QK peptides demonstrated that
      the conjugation efficiency to ELP hydrogels was >75% and that covalent
      immobilization effectively eliminates all QK diffusion. Compared with pristine
      ELP hydrogels, human umbilical vein endothelial cell (HUVEC) proliferation was
      significantly enhanced on ELP hydrogels immobilized with 10 nM or 1 MUM QK.
      Moreover, upon encapsulation within tethered QK-ELP hydrogels, HUVEC spheroids
      maintained near 100% viability and demonstrated significantly more three
      dimensional outgrowth compared to those supplemented with soluble QK peptide at
      the same concentration. These results encourage the further development of
      protein-engineered scaffolds decorated with growth-factor-mimetic peptides to
      provide long-term biological signals using this versatile, single-step synthesis.

PMID- 24729869
TI  - Glycoprotein CD98 as a receptor for colitis-targeted delivery of nanoparticle.
AB  - Treatment strategies for inflammatory bowel disease have been constrained by
      limited therapeutic efficacy and serious adverse effects owing to a lack of
      receptor for targeted drug delivery to the inflamed colon. Upon inflammation,
      CD98 expression is highly elevated in colonic epithelial cells and infiltrating
      immune cells. To investigate whether CD98 can be used as a colitis-targeted
      delivery receptor, we constructed CD98 Fab'-bearing quantum dots (QDs)-loaded
      nanoparticles (Fab'-NPs). The resultant Fab'-NPs had desired particle size (~458
      nm) with a narrow size distribution and zeta-potential (approximately +19 mV),
      low cytotoxicity, and excellent fluorescence properties. Electron microscopy
      images provided direct evidence for the well-dispersed distribution of QDs within
      spherical Fab'-NPs. Cellular uptake experiments demonstrated that Fab'-NPs were
      efficiently internalized into Colon-26 and RAW 264.7 cells through the CD98
      mediated endocytosis pathway, and showed that the targeting effect of CD98 Fab'
      markedly increased their cellular uptake efficiency compared with control
      pegylated QDs-loaded NPs (PEG-NPs). Furthermore, ex vivo studies showed much more
      effective accumulation of Fab'-NPs in colitis tissue than that of PEG-NPs. These
      findings suggest that because of inflammation-dependent over-expression of CD98,
      active colitis-targeted delivery can be accomplished using NPs decorated with
      CD98 antibody.

PMID- 24729870
TI  - Engaging adaptive immunity with biomaterials.
AB  - Adaptive immune responses, characterized by T cells and B cells engaging and
      responding to specific antigens, can be raised by biomaterials containing
      proteins, peptides, and other biomolecules. How does one avoid, control, or
      exploit such responses? This review will discuss major properties and processes
      that influence biomaterials-directed adaptive immunity, including the physical
      dimensions of a material, its epitope content, and its multivalency. Selected
      strategies involving novel biomaterials designs will be discussed to illustrate
      these points of control. Specific immunological processes that biomaterials are
      being developed to direct will be highlighted, including minimally inflammatory
      scaffolds for tissue repair and immunotherapies eliciting desired B cell
      (antibody) responses, T cell responses, or tolerance. The continuing development
      of a knowledge base for specifying the strength and phenotype of biomaterials
      mediated adaptive immune responses is important, not only for the engineering of
      better vaccines and immunotherapies, but also for managing immune responses
      against newer generations of increasingly biological and biomolecular materials
      in contexts such as tissue repair, tissue engineering, or cell delivery.

PMID- 24729872
TI  - Hepatitis B vaccination and screening awareness in primary care practitioners.
AB  - Introduction. The goals of Healthy People US 2020 have called for increased
      screening and vaccination of high-risk groups for Hepatitis B (HBV). Methods. We
      performed a survey of 400 randomly chosen primary care practitioners (PCPs) in
      Wisconsin to assess their knowledge, attitudes, and practices regarding screening
      and vaccination for HBV. Results. Screening rates of patients at risk of sexual
      transmission were low, with 61% of respondents stating that they screen patients
      who had more than 1 sex partner in 6 months and 86% screening patients with a
      history of sex with prostitutes. Screening rate for persons with a history of
      intravenous drug use was 94%. Children of immigrants were screened by 65%,
      persons on hemodialysis by 73%, and prison inmates by 69%. Screening increased
      with provider experience with HBV. Deficiencies in vaccination rates mirrored
      screening practices. Major barriers to screening were cost, someone else's
      responsibility, time constraints, or lack of knowledge. Conclusions. Without
      improved education and practices of PCPs about HBV screening and vaccination, the
      goals of healthy people 2020 regarding HBV will not be met. Barriers to screening
      and vaccination need to be addressed. Cost-effectiveness of alternative
      strategies such as universal vaccination under the age of 50 should be explored. 

PMID- 24729871
TI  - Polyphosphazenes: Multifunctional, Biodegradable Vehicles for Drug and Gene
      Delivery.
AB  - Poly[(organo)phosphazenes] are a unique class of extremely versatile polymers
      with a range of applications including tissue engineering and drug delivery, as
      hydrogels, shape memory polymers and as stimuli responsive materials. This review
      aims to divulge the basic principles of designing polyphosphazenes for drug and
      gene delivery and portray the huge potential of these extremely versatile
      materials for such applications. Polyphosphazenes offer a number of distinct
      advantages as carriers for bioconjugates; alongside their completely degradable
      backbone, to non-toxic degradation products, they possess an inherently and
      uniquely high functionality and, thanks to recent advances in their polymer
      chemistry, can be prepared with controlled molecular weights and narrow
      polydispersities, as well as self-assembled supra-molecular structures.
      Importantly, the rate of degradation/hydrolysis of the polymers can be carefully
      tuned to suit the desired application. In this review we detail the recent
      developments in the chemistry of polyphosphazenes, relevant to drug and gene
      delivery and describe recent investigations into their application in this field.

PMID- 24729873
TI  - Converting potential abdominal hysterectomy to vaginal one: laparoscopic assisted
      vaginal hysterectomy.
AB  - Background. The idea of laparoscopic assisted vaginal hysterectomy (LAVH) is to
      convert a potential abdominal hysterectomy to a vaginal one, thus decreasing
      associated morbidity and hastening recovery. We compared intraoperative and
      postoperative outcomes between LAVH and abdominal hysterectomy, to find out if
      LAVH achieves better clinical results compared with abdominal hysterectomy.
      Material and methods. A total of 48 women were enrolled in the study. Finally 17
      patients underwent LAVH (cases) and 20 underwent abdominal hysterectomy
      (controls). All surgeries were performed by a set of gynecologists with more or
      less same level of surgical experience and expertise. Results.None of the
      patients in LAVH required conversion to laparotomy. Mean operating time was 30
      minutes longer in LAVH group as compared to abdominal hysterectomy group (167.06
      + 31.97 min versus 135.25 + 31.72 min; P < 0.05). However, the mean blood loss in
      LAVH was 100 mL lesser than that in abdominal hysterectomy and the difference was
      found to be statistically significant (248.24 + 117.79 mL versus 340.00 + 119.86
      mL; P < 0.05). Another advantage of LAVH was significantly lower pain scores on
      second and third postoperative days. Overall complications and postoperative
      hospital stay were not significantly different between the two groups. 

PMID- 24729874
TI  - Structural Stereochemistry of Androstene Hormones Determines Interactions with
      Human Androgen, Estrogen, and Glucocorticoid Receptors.
AB  - DHEA, 17alpha-AED, 17beta-AED, and 17beta-AET exhibit strong biological activity
      that has been attributed to androgenic, estrogenic, or antiglucocorticoid
      activity in vivo and in vitro. This study compared DHEA, 17alpha-AED, 17beta-AED,
      and 17beta-AET for their ability to activate the human AR, ER, and GR and
      determine the relative androgenicity, estrogenicity, and glucocorticoid activity.
      The results show that, at the receptor level, these androstene hormones are weak
      AR and even weaker ER activators. Direct androstene hormone activation of the
      human AR, ERalpha, and ERbeta may not be essential for their biological function.
      Similarly, these hormones indirectly activated the human GR, only in the presence
      of high dexamethasone concentrations. These results underscore the major
      difference between androstene hormone interactions with these nuclear receptors
      and their biological effects.

PMID- 24729875
TI  - Costs of formal and informal home care and quality of life for patients with
      multiple sclerosis in sweden.
AB  - Disease progression in multiple sclerosis leads to dramatic changes in a person's
      ability to perform daily activities and increases reliance on external help. This
      study aims to describe and to estimate costs of formal/informal home care and
      quality of life related to multiple sclerosis. A mailed survey to a random sample
      of MS sufferers (n = 1500) collected data on the number of hours of home care
      received, type of help, productivity losses, quality of life, and disease
      characteristics. Costs for home care were estimated in 2012 ? and factors that
      may influence the likelihood of getting home care were also evaluated. Formal
      care was given to 27% of the respondents (n = 839) at an average of 238.7
      hrs/month at a mean monthly cost of ?2873/person with MS. Informal care was
      received by 49% of the respondents at an average of 47.3 hrs/month at a mean
      monthly cost of ?389/person with MS. Utilities across disease severity are as
      follows: mild MS = 0.709 (sd = 0.233), moderate MS = 0.562 (sd = 0.232), and
      severe MS = 0.284 (sd = 0.283). Total home care costs increased with increasing
      disease severity. Informal caregiving contributes significantly to MS home care
      in Sweden. 

PMID- 24729876
TI  - Does Statin or ASA Affect Survival When Prostate Cancer Is Treated with External
      Beam Radiation Therapy?
AB  - Background. Prior studies evaluating the effect of statins or acetylsalicylic
      acid (ASA) on the survival of men receiving prostate cancer were treatment have
      reported conflicting results, and have not adjusted for comorbidity. Our aim is
      to investigate the influence of statins and ASA on prostate cancer survival, when
      comorbidity is adjusted for, in men treated with external beam radiation therapy
      (EBRT) for prostate cancer. Methods. A cohort of 3851 patients with prostate
      cancer treated with curative EBRT +/- androgen deprivation therapy (ADT) between
      2000 and 2007. Stage, treatment, medication use, and Charlson comorbidity index
      (CCI) scores were analyzed. Results. Median followup was 8.4 years. Mean age was
      70.3 years. Neoadjuvant ADT was used in 67%. Statins were used in 23%, ASA in
      24%, and both in 11%. Comorbidity scores were 0 in 65%, 1 in 25%, and >=2 in 10%
      of patients. Statin and ASA use were associated with increased age and
      comorbidity. Although statin and ASA use were significantly associated with
      improved prostate cancer specific survival (PCSS) on univariate analysis, neither
      were on multivariate analysis. Conclusion. Neither statin nor ASA use impacted
      PCSS on multivariate competing risks analysis. Survival was impacted by increased
      comorbidity as well as statin and ASA use. 

PMID- 24729877
TI  - Development of polyps and cancer in patients with a negative colonoscopy: a
      follow-up study of more than 20 years.
AB  - Background. Adenomas are missed during colonoscopy. Aim. Assess the occurrence of
      colorectal cancer (CRC) and polyps in patients with a negative index colonoscopy
      (IC). Patients and Methods. All patients with a IC in 1992-1994, aged 40 and 60
      years, were included. Exclusion criterion was presence of abnormalities, a family
      history, or surveillance. At the end of 2013 all records were studied in order to
      gather follow-up information. Results. 394 patients were included in four groups:
      group 1 patients who died, group 2 patients who were not in the hospital systems
      anymore, group 3 patients still visiting the hospital but not the department of
      gastroenterology, and group 4 patients undergoing new colonoscopies. In group 1,
      2 patients died of CRC and 4 developed a polyp. No data were available from the
      patients in group 2. Patients in group 3 visited the outpatient clinics but did
      not undergo new colonoscopy. Patients in group 4 underwent additional
      colonoscopies. The yield was 35 patients polyps and three CRCs. Five patients
      (1.3%) developed CRC, and 39 (9%) developed a polyp. Conclusion. Given these
      results the number of potentially missed adenomas in IC is very low and the
      consequences of missed adenomas are highly exaggerated. 

PMID- 24729879
TI  - Role of pentoxifylline and sparfloxacin in prophylaxis of spontaneous bacterial
      peritonitis in cirrhotic patients.
AB  - This study was directed to evaluate the role of sparfloxacin and pentoxifylline
      in the prophylaxis of spontaneous bacterial peritonitis in cirrhotic patients.
      Forty cirrhotic patients with ascites were included in the study. Patients were
      randomized into four groups in a blind fashion; each group consists of ten
      patients. Group one received ciprofloxacin (control group), group two received
      sparfloxacin, group three received pentoxifylline, and group four received a
      combination of sparfloxacin and pentoxifylline. Treatment duration was six
      months. Serum TNF- alpha level was the primary inflammatory marker of the study
      to evaluate the effect of the used medications. In group two, TNF- alpha level
      showed a statistically significant decrease in comparison with group one (P =
      0.001), while in group three, TNF- alpha level showed nonsignificant difference
      in comparison with the control group (P > 0.05). In addition, group four showed a
      statistically significant decrease in TNF- alpha level compared to the other
      three groups (P < 0.05). The finding from our study indicates that sparfloxacin
      as well as pentoxifylline could be used in prophylaxis of spontaneous bacterial
      peritonitis. Combination of sparfloxacin and pentoxifylline showed some of
      synergism which may be useful in decreasing emergence of resistant strains. 

PMID- 24729880
TI  - A Retrospective Case-Control Study Evaluating the Bowel Preparation Quality
      during Surveillance Colonoscopy after Colonic Resection.
AB  - Purpose. Bowel preparation for surveillance endoscopy following surgery can be
      impaired by suboptimal bowel function. Our study compares two groups of patients
      in order to evaluate the influence of colorectal resection on bowel preparation.
      Methods. From April 2010 to December 2011, 351 patients were enrolled in our
      retrospective study and divided into two homogeneous arms: resection group (RG)
      and control group. Surgical methods were classified as left hemicolectomy, right
      hemicolectomy, anterior rectal resection, and double colonic resection. Bowel
      cleansing was evaluated by nine skilled endoscopists using the Aronchick scale.
      Results. Among the 161 patients of the RG, surgery was as follows: 60 left
      hemicolectomies (37%), 62 right hemicolectomies (38%), and 33 anterior rectal
      resections (20%). Unsatisfactory bowel preparation was significantly higher in
      resected population (44% versus 12%; P value = 0.000). No significant difference
      (38% versus 31%, P value = ns) was detected in the intermediate score, which
      represents a fair quality of bowel preparation. Conclusions. Our study highlights
      how patients with previous colonic resection are at high risk for a worse bowel
      preparation. Currently, the intestinal cleansing carried out by 4 L PEG based
      preparation does not seem to be sufficient to achieve the quality parameters
      required for the post-resection endoscopic monitoring. 

PMID- 24729878
TI  - Epigenetic biomarkers: potential applications in gastrointestinal cancers.
AB  - Genetics and epigenetics coregulate the cancer initiation and progression.
      Epigenetic mechanisms include DNA methylation, histone modification, chromatin
      remodeling, and noncoding RNAs. Aberrant epigenetic modifications play a
      fundamental role in the formation of gastrointestinal cancers. Advances in
      epigenetics offer a better understanding of the carcinogenesis and provide new
      insights into the discovery of biomarkers for diagnosis, and prognosis prediction
      of human cancers. This review aims to overview the epigenetic aberrance and the
      clinical applications as biomarkers in gastrointestinal cancers mainly gastric
      cancer and colorectal cancer. 

PMID- 24729881
TI  - Pretransplant comorbidities maintain their impact on allogeneic stem cell
      transplantation outcome 5 years posttransplant: a retrospective study in a single
      german institution.
AB  - The introduction of reduced-intensity conditioning regimens has allowed elderly
      patients with preexisting comorbidities access to the potentially curative
      allogeneic stem cell transplantation. Patient's comorbidities at the time of
      treatment consideration play a significant role in transplant outcome in terms of
      both overall survival (OS) and nonrelapse mortality (NRM). The hematopoietic stem
      cell transplantation comorbidity index (HCT-CI) quantifies these patient specific
      risks and has established itself as a major tool in the pretransplant assessment
      of patients. Many single center and multicenter studies have assessed the HCT-CI
      score and reported conflicting outcomes. The present study aimed to evaluate the
      HCT-CI in a single large European transplant centre. 245 patients were
      retrospectively analyzed and the predictive value of the score was assessed with
      respect to OS and NRM. We confirm that the HCT-CI predicts outcome for both OS
      and NRM. Moreover, we identified age of the patient as an independent prognostic
      parameter for OS. Incorporation of age in the HCT-CI would improve its ability to
      prognosticate and allow the transplant physician to assess the patient specific
      risks appropriately at the time of counseling for transplant. 

PMID- 24729882
TI  - Postnatal systemic blood flow in neonates with abnormal fetal umbilical artery
      Doppler.
AB  - Objective. Abnormal umbilical artery Doppler (UAD) studies are associated with
      poor neonatal outcomes. We sought to determine if postnatal measures of systemic
      blood flow (SBF), as measured by functional echocardiography (fECHO), could
      identify which fetuses with abnormal UAD were at the highest risk of adverse
      outcomes. Study Design. This is a retrospective review of fetuses with abnormal
      UAD who received fECHO in the first 72 hours of life. Measures of SBF (right
      ventricular output (RVO) and superior vena cava (SVC) flow) were performed and
      compared with prenatal variables and postnatal outcomes. Result. 63 subjects had
      abnormal UAD, 20 of which also had fECHO. Six subjects had abnormal flow.
      Gestational age at delivery was similar between the two groups. Those with
      abnormal SBF had fewer days of abnormal UAD prior to delivery and developed RDS
      (P < 0.001). Conclusion. Postnatal measures of SBF were associated with poor
      postnatal outcomes in fetuses with abnormal UAD. Future studies incorporating
      antenatal measures of SBF may help obstetricians determine which pregnancies
      complicated by UAD are likely to have postnatal morbidity. 

PMID- 24729883
TI  - The Effect of Gynostemma pentaphyllum Extract on Mouse Dermal Fibroblasts.
AB  - Background. The objective of this paper is to demonstrate the effect of
      Gynostemma pentaphyllum extract on mouse dermal fibroblasts. Recent studies have
      shown that this plant may possess great antioxidant properties, which can be very
      beneficial in combating oxidative stress. Methods. Gynostemma pentaphyllum
      extract was prepared and mouse dermal fibroblasts were obtained and cultured as
      per our laboratory protocols. Twelve samples of cells were cultured under the
      same conditions and both negative and positive controls were established.
      Induction of oxidative stress was carried out using ultraviolet C (UVC) light.
      Viable cell count was carried out, using microscopy. The analysis of the overall
      results was processed using SPSS version 16.0. Results. Statistical analysis
      showed strong positive correlation between the concentration of Gynostemma
      pentaphyllum and the mean duration of cell viability (rs = 1), with a high level
      of statistical significance (P < 0.01). Likewise, strong positive correlation
      existed between trials of cell viability (rs = 0.988-1), with statistical
      significance (P < 0.01). Conclusion. Gynostemma pentaphyllum extract prolongs
      viability of mouse dermal fibroblasts damaged by UVC light-induced oxidative
      stress. The results show the potential benefits of this extract on dermal cell
      aging. 

PMID- 24729884
TI  - Correlation between Body Mass Index and Waist Circumference in Patients with
      Metabolic Syndrome.
AB  - Metabolic syndrome is defined as a group of coexisting metabolic risk factors,
      such as central obesity, lipid disorders, carbohydrate disorders, and arterial
      hypertension. According to the 2005 IDF criteria, subsequently revised in 2009,
      abdominal obesity is identified as the waist circumference of >=80 cm in women
      and >=94 cm in men. It is responsible for the development of insulin resistance.
      The aim of our study was to demonstrate a correlation between waist circumference
      (WC) and body mass index (BMI) in patients with metabolic syndrome in relation
      with hypertension, lipid disorders, and carbohydrate disorders. A cross-sectional
      two-site study was conducted in the Kuyavian-Pomeranian Voivodeship for 24
      months. The study group consisted of 839 patients with diagnosed metabolic
      syndrome: 345 men (41.1%) and 494 women (58.9%) aged 32-80. In the study group,
      WC was found to be significantly correlated with BMI (R = 0.78, P < 0.01). The
      presence of overweight in men (BMI 25, 84 kg/m(2)) and even normal body weight in
      women (BMI 21,62 kg/m(2)) corresponds to an increased volume of visceral tissue
      in the abdomen. Introduction of primary prophylaxis in those people to limit the
      development of diabetes mellitus type 2 and cardiovascular diseases should be
      considered. 

PMID- 24729885
TI  - Lower plasma creatinine and urine albumin in individuals at increased risk of
      type 2 diabetes with factor v leiden mutation.
AB  - The factor V Leiden (FVL) mutation is the most frequent genetic cause of venous
      thrombosis in Caucasians. However, protective effects have been suggested to
      balance the disadvantages. We have recently observed protective effects of FVL
      mutation on experimental diabetic nephropathy in mice as well as an association
      with reduced albuminuria in two human cohorts of diabetic patients. In the
      present study we aimed to reevaluate these findings in an independent, larger
      cohort of 1905 Caucasians at risk of developing type 2 diabetes and extend
      possible associations to earlier disease stages of nephropathy. Carriers of FVL
      mutation had a significantly lower urine albumin excretion (P = 0.03) and tended
      to have lower plasma creatinine concentrations (P = 0.07). The difference in
      plasma creatinine concentrations was significant after adjustment for the
      influencing factors: age, gender, and lean body mass (P = 0.048). These
      observations at a very early "disease" stage are an important extension of
      previous findings and suggest that modification of glomerular dysfunction by FVL
      mutation is relevant during very early stages of diabetic nephropathy. This makes
      the underlying mechanism an interesting therapeutic target and raises the
      question whether FVL mutation may also exert protective effects in other
      glomerulopathies. 

PMID- 24729886
TI  - Effect of Aerobic Training on Glucose Control and Blood Pressure in T2DDM East
      African Males.
AB  - Background. Exercise training intervention is underused in the management of type
      2 diabetes mellitus in East Africa. Methods. 41 physically-active males with type
      2 diabetes mellitus living in Mozambique were recruited and randomly assigned to
      12 weeks of supervised exercise of low intensity exercise (LEX), vigorous
      intensity exercise (VEX), or to a control group (CON). Since there were no
      differences for any outcome variables between the exercise groups, VEX and LEX
      were combined into one exercise group (EX). Results. Age and baseline body weight
      were similar between EX and CON. Plasma glucose at 120 min following glucose load
      (Glu 120) was significantly reduced in the EX group after training (Glu 120 :
      17.3 mmol/L to 15.0 mmol/L, P < 0.05), whereas Glu 120 remained unchanged in the
      CON (Glu 120 : 16.6 mmol/L to 18.7 mmol/L). After controlling for baseline blood
      pressure (BP), posttraining systolic BP and diastolic BP were lower in the EX
      group than in the CON group (EX: 129/77 mm Hg, CON: 152/83 mm Hg, P < 0.05).
      Conclusion. Adding exercise to already active African men with type 2 diabetes
      improved glucose control and BP levels without concomitant changes in weight. 

PMID- 24729887
TI  - Heavy metal levels in adolescent and maternal blood: association with risk of
      hypospadias.
AB  - Background. Hypospadias is a part of testicular digenesis syndrome (TDS) which
      includes infertility, cryptorchidism, and spermatogenesis. Heavy metals act as
      endocrine disrupting compounds. Heavy metals such as cadmium, chromium, arsenic,
      and lead have been associated with male infertility, cryptorchidism,
      spermatogenesis, cancer, reproductive disorder, and neurological disorder.
      However, it remains an important issue to corroborate or refute the hypothesis
      that the role of heavy metals in male reproductive tract disorders. Hence, the
      present study was designed to investigate the possible association of heavy metal
      and risk of hypospadias by estimating the blood heavy metal levels. Methods. In
      this case control study, 50 hypospadias boys diagnosed and confirmed by a
      pediatric urologist and 50 randomly selected age-matched (1-5 years) healthy
      control boys not suffering from any clinically detectible illness and their
      mothers have been included and heavy metal levels in the blood of these subjects
      have been estimated by Atomic Absorption Spectrophotometer (AAS). Result.
      Significantly high levels of cadmium and lead have been observed in hypospadias
      cases; however, all heavy metal levels were present in higher concentration.
      Conclusion. Higher blood levels of cadmium and lead may be associated with the
      increased risk of hypospadias. 

PMID- 24729888
TI  - Both castration and goserelin acetate ameliorate myocardial ischemia reperfusion
      injury and apoptosis in male rats.
AB  - Although reperfusion of an ischemic organ is essential to prevent irreversible
      tissue damage, it may amplify tissue injury. This study investigates the role of
      endogenous testosterone in myocardial ischemia reperfusion and apoptosis in male
      rats. Material and method. Twenty four male rats were randomized into 4 equal
      groups: Group (1), sham group, rats underwent the same anesthetic and surgical
      procedure as the control group except for LAD ligation; Group (2), Active control
      group, rats underwent LAD ligation; Group (3), castrated, rats underwent surgical
      castration, left 3wks for recovery, and then underwent LAD ligation; and Group
      (4), Goserelin acetate treated, rats received 3.6 mg of Goserelin 3 wks before
      surgery and then underwent LAD ligation. At the end of experiment, plasma cTn I,
      cardiac TNF- alpha , IL1- beta , ICAM-1, and Apoptosis level were measured and
      histological examination was made. Results. Compared to sham group, the levels of
      myocardial TNF- alpha , IL-1 beta , ICAM-1, apoptosis, and plasma cTn I were
      significantly increased (P < 0.05) in control group and all rats showed
      significant myocardial injury (P < 0.05). Castration and Goserelin acetates
      significantly counteract the increase in myocardial levels of TNF- alpha , IL-1
      beta , ICAM-1, plasma cTn I, and apoptosis (P < 0.05) and significantly reduce (P
      < 0.05) the severity of myocardial injury. We conclude that castration and
      Goserelin acetates ameliorate myocardial I/R injury and apoptosis in rats via
      interfering with inflammatory reactions. 

PMID- 24729889
TI  - Efficacy of Composite Extract from Leaves and Fruits of Medicinal Plants Used in
      Traditional Diabetic Therapy against Oxidative Stress in Alloxan-Induced Diabetic
      Rats.
AB  - Oxidative stress plays a vital role in diabetic complications. To suppress the
      oxidative stress mediated damage in diabetic pathophysiology, a special focus has
      been given on composite extract (CE) and making small dose of naturally occurring
      antidiabetic plants leaf and fruits. The aim of the present study was to evaluate
      the beneficial role of CE against alloxan- (ALX-) induced diabetes of Wistar
      strain rats. A dose-dependent study for CE (25, 50, and 100 mg/kg body weight)
      was carried out to find the effective dose of the composite compound in ALX
      induced diabetic rats. ALX exposure elevated the blood glucose, plasma advanced
      oxidation product (AOPP), sialic acid demonstrating disturbed antioxidant
      status.CE at a dose of 100 mg/kg body weight restored/minimised these alterations
      towards normal values. In conclusion, small dose of CE possesses the capability
      of ameliorating the oxidative stress in ALX-induced diabetes and thus could be a
      promising approach in lessening diabetic complications. 

PMID- 24729890
TI  - Therapeutic Effects of Acetone Extract of Saraca asoca Seeds on Rats with
      Adjuvant-Induced Arthritis via Attenuating Inflammatory Responses.
AB  - Saraca asoca has been traditionally used in Indian system for treatment of
      uterine, genital, and other reproductive disorders in women, fever, pain, and
      inflammation. The hypothesis of this study is that acetone extract of Saraca
      asoca seeds is an effective anti-inflammatory treatment for arthritis in animal
      experiments. The antiarthritic effect of its oral administration on Freund's
      adjuvant-induced arthritis has been studied in Wistar albino rats after acute and
      subacute toxicities. Phytochemical analysis revealed presence of high
      concentrations of phenolic compounds such as flavonoids and tannins, while no
      mortality or morbidity was observed up to 1000 mg/kg dose during acute and
      subacute toxicity assessments. Regular treatment up to 21 days of adjuvant
      induced arthritic rats with Saraca asoca acetone extract (at 300 and 500 mg/kg
      doses) increases RBC and Hb, decreases WBC, ESR, and prostaglandin levels in
      blood, and restores body weight when compared with control (normal saline) and
      standard (Indomethacin) groups. Significant (P < 0.05) inhibitory effect was
      observed especially at higher dose on paw edema, ankle joint inflammation, and
      hydroxyproline and glucosamine concentrations in urine. Normal radiological
      images of joint and histopathological analysis of joint, liver, stomach, and
      kidney also confirmed its significant nontoxic, antiarthritic, and anti
      inflammatory effect. 

PMID- 24729891
TI  - Nonmotor symptoms in early- and advanced-stage Parkinson's disease patients on
      dopaminergic therapy: how do they correlate with quality of life?
AB  - To determine the impact of nonmotor symptoms (NMS) on health-related quality of
      life (HRQoL) we examined 100 Parkinson's disease (PD) patients on dopaminergic
      medications. An "early-stage" (ES) and an "advanced-stage" (AS) groups were
      formed. HRQoL was established by the questionnaire PDQ-8, number of NMS by
      NMSQuest, and severity and frequency of NMS by the assessment scale NMSS. The
      total NMS averaged 11.3 (ES = 9.6, AS = 12.8). The NMSS domain correlation
      profiles for ES and AS did not fundamentally differ; however, the domains
      attention/memory and mood/apathy correlated moderately to strongly with HRQoL in
      ES, while the sleep/fatigue domain correlated moderately with HRQoL in AS. Weakly
      correlating domains were sleep/fatigue in ES and cardiovascular,
      attention/memory, and mood/apathy domains in AS. In view of these findings we
      strongly recommend systematic, active screening and therapy for neuropsychiatric
      disorders (mood, cognitive and sleep disorders, and fatigue) at the initial
      diagnosis and throughout the entire course of PD. 

PMID- 24729892
TI  - Minimizing technical failure of percutaneous balloon compression for trigeminal
      neuralgia using neuronavigation.
AB  - Objective. Percutaneous balloon compression (PBC) is an effective and safe
      management for medically refractory trigeminal neuralgia; however, technical
      failure to cannulate the foramen ovale (FO) using only fluoroscopy is a
      significant problem in some cases. In this paper, we suggest the use of
      intraoperative navigation, in cases of reoperation due to prior technical failure
      to cannulate the FO under fluoroscopy. Methods. A total of 174 patients underwent
      PBC for TN since 2003. In 9 cases the penetration of the FO was not accomplished.
      Five of those patients were reoperated on for PBC using navigation from March
      2012 to September 2012. SURGICAL TECHNIQUE: preoperatively, a head Computed
      Tomography (CT) scan is performed and the acquired images are imported into the
      navigation system. Intraoperatively, a small reference frame is strapped firmly
      to the patient's forehead, the CT images are registered, and cannulation is
      performed under the guidance of the navigation system. Results. In all patients,
      the operation overall was completed successfully. Moreover, all patients reported
      complete pain relief immediately postoperatively and no complications were
      recorded overall. Conclusions. We suggest the use of neuronavigation in cases of
      technical failure of PBC. That technique involves technology with significant
      advantages helping the successful cannulation of the FO and seems more efficient
      and safer.

PMID- 24729893
TI  - Evaluating different aspects of prospective memory in amnestic and nonamnestic
      mild cognitive impairment.
AB  - Prospective memory, the inability to remember an intended action, is a common
      complaint, but not formally assessed in most clinical and research studies of
      mild cognitive impairment (MCI). In this study, patients with amnestic mild
      cognitive impairment (aMCI), non-amnestic cognitive impairment (naMCI), and
      cognitively normal (CN) elders were assessed using the Miami Prospective Memory
      Test (MPMT). A unique aspect of the paradigm was that participants were scored
      for intention to perform, accuracy in recollection for specific elements of the
      task, and the need for reminder cues. Excellent test-retest stability was
      obtained for MPMT Event-Related (ER), combined Time-Related (TR) subscales, and
      total MPMT score for aMCI subjects. MPMT impairments were observed in 48.6% of
      aMCI, 29.4% of naMCI, and 10.0% of normal elderly participants. Prospective
      memory deficits were common in participants with aMCI, and occurred in almost a
      third of naMCI participants. Intention to perform and need for reminder cues were
      significantly more impaired than retrospective memory for specific details of the
      task. It is concluded that assessment of different elements of prospective memory
      is important in MCI research and that inability to remember intended actions is a
      significant feature in those as risk for Alzheimer's disease. 

PMID- 24729894
TI  - Association of mammographic breast density with dairy product consumption, sun
      exposure, and daily activity.
AB  - Background. Mammographic density is a risk factor, for breast cancer and its
      association with various factors is under investigation; we carried out a study
      to assess its relationship with daily dairy intake, sun exposure, and physical
      activities. Patients and Methods. Women >=40 years of age were interviewed about
      habits of dairy product consumption, daily sun exposure and physical activity.
      Exclusion criteria consisted of history of breast cancer, consumption of calcium
      and vitamin D supplements, hormone replacement therapy, or renal disease.
      Mammographic densities were classified according to the classification system of
      the American College of Radiologists into 4 classes. Results. Overall 703 cases
      were entered in the study. The mean age was 48.2 +/- 6.2 years. The most common
      and least frequent classes of mammographic density were classes 2 and 4,
      respectively. There was no significant association between mammographic density
      and rate of dairy consumption, amount of sunlight exposure, and daily physical
      activity. Conclusion. Relation of sunlight exposure and intake of milk products
      with mammographic density need further study, while the subject of physical
      activity can be evaluated by a systematic review and meta-analysis of the
      existing literature. 

PMID- 24729895
TI  - Frequency and Spectrum of KRAS Mutations in Moroccan Patients with Lung
      Adenocarcinoma.
AB  - Background. In lung adenocarcinoma, the frequency of KRAS mutations is ethnicity
      dependent with a higher proportion in African Americans and white Caucasians than
      in Asians. The prevalence of these mutations among North Africans patients is
      unknown. The objective of this study was to report the frequency and spectrum of
      KRAS mutations in a group of Moroccan lung adenocarcinoma patients. Methods.
      Tumor specimens from 117 Moroccan patients with lung adenocarcinoma were selected
      to determine frequency and spectrum of KRAS mutations. KRAS mutations in codons
      12 and 13 of exon 2 were analyzed using conventional DNA sequencing. Results. The
      overall frequency of the KRAS mutations was 9% (11/117). In the population with
      KRAS mutations, there was a trend towards more male (P = 0.06) and more smokers
      (P = 0.08) compared to patients with wild type KRAS. KRAS mutations were located
      at codon 12 in 10 out of 11 patients (91%). The G12C mutation was the most
      frequent KRAS mutation (73%). Conclusion. This is the first study to date
      examining the frequency and spectrum of KRAS mutations in lung adenocarcinomas in
      North African and Arab populations. KRAS mutation frequency in Moroccan patients
      was comparable with the frequency observed in East-Asian population. KRAS
      mutations are more likely observed in males and smokers and to be transversions.
      Further studies, in larger numbers of patients, are needed to confirm these
      findings. 

PMID- 24729897
TI  - Undiagnosed diabetes in breast, colorectal, lung, and prostate cancer: incidence
      and risk factors.
AB  - Our study describes the incidence and risk factors for undiagnosed diabetes in
      elderly cancer patients. Using Surveillance, Epidemiology, and End Results
      Medicare data, we followed patients with breast, colorectal, lung, or prostate
      cancer from 24 months before to 3 months after cancer diagnosis. Medicare claims
      were used to exclude patients with diabetes 24 to 4 months before cancer (look
      back period), identify those with diabetes undiagnosed until cancer, and
      construct indicators of preventive services, physician contact, and comorbidity
      during the look-back period. Logistic regression analyses were performed to
      identify factors associated with undiagnosed diabetes. Overall, 2,678 patients
      had diabetes undiagnosed until cancer. Rates were the highest in patients with
      both advanced-stage cancer and low prior primary care/medical specialist contact
      (breast 8.2%, colorectal 5.9%, lung 4.4%). Nonwhite race/ethnicity, living in a
      census tract with a higher percent of the population in poverty and a lower
      percent college educated, lower prior preventive services use, and lack of
      primary care and/or medical specialist care prior to cancer all were associated
      with higher (P <= 0.05) adjusted odds of undiagnosed diabetes. Undiagnosed
      diabetes is relatively common in selected subgroups of cancer patients, including
      those already at high risk of poor outcomes due to advanced cancer stage. 

PMID- 24729896
TI  - Public awareness of colorectal cancer screening: knowledge, attitudes, and
      interventions for increasing screening uptake.
AB  - Colorectal cancer ranks as one of the most incidental and death malignancies
      worldwide. Colorectal cancer screening has proven its benefit in terms of
      incidence and mortality reduction in randomized controlled trials. In fact, it
      has been recommended by medical organizations either in average-risk or family
      risk populations. Success of a screening campaign highly depends on how compliant
      the target population is. Several factors influence colorectal cancer screening
      uptake including sociodemographics, provider and healthcare system factors, and
      psychosocial factors. Awareness of the target population of colorectal cancer and
      screening is crucial in order to increase screening participation rates.
      Knowledge about this disease and its prevention has been used across studies as a
      measurement of public awareness. Some studies found a positive relationship
      between knowledge about colorectal cancer, risk perception, and attitudes
      (perceived benefits and barriers against screening) and willingness to
      participate in a colorectal cancer screening campaign. The mentioned factors are
      modifiable and therefore susceptible of intervention. In fact, interventional
      studies focused on average-risk population have tried to increase colorectal
      cancer screening uptake by improving public knowledge and modifying attitudes. In
      the present paper, we reviewed the factors impacting adherence to colorectal
      cancer screening and interventions targeting participants for increasing
      screening uptake. 

PMID- 24729898
TI  - Pediatric sclerosing rhabdomyosarcomas: a review.
AB  - Sclerosing RMS (SRMS) is a recently described subtype of RMS that has not yet
      been included in any of the classification systems for RMSs. We did pubmed search
      using keywords "sclerosing, and rhabdomyosarcomas" and included all pediatric
      cases (age <= 18 years) of SRMSs in this review. We also included our case of an
      eleven-year-old male child with skull base SRMS and discuss the clinical,
      histopathological, immunohistochemical, and genetic characteristics of these
      patients. Till now, only 20 pediatric cases of SRMSs have been described in the
      literature. Pediatric SRMS more commonly affects males at a mean age of 9 years.
      Extremeties and head/neck regions were most commonly affected. Follow-up details
      were available for 16 patients with mean follow-up of 25.3 months. Treatment
      failure rate was 43.75%. Overall amongst these 16 patients, 10 were alive without
      disease, 4 were alive with disease, and two died. Thus, overall and disease-free
      survival amongst these 16 patients were 87.5% and 62.5%, respectively. The
      literature regarding clinical behaviour and outcome of pediatric patients with
      SRMSs is patchy. Detailed molecular/genetic analysis and clinicopathological
      characterization with longer follow-ups of more cases may throw some light on
      this possibly new subtype of RMS. 

PMID- 24729899
TI  - Optic disc hemorrhage after phacoemulsification in patients with glaucoma.
AB  - Background. Optic disk hemorrhage is known to be a risk factor for glaucoma
      progression. Cataract surgery by phacoemulsification results in large intraocular
      pressure fluctuations. We aim to investigate whether phacoemulsification is
      associated with optic disc hemorrhage in patients with glaucoma. Methods. This is
      a retrospective review of consecutive university clinic based glaucoma patients
      undergoing phacoemulsification alone, with at least 3 visits in the year before
      and at least 5 visits in the year following phacoemulsification. The presence of
      optic disk hemorrhage was evaluated with slit lamp biomicroscopy at each clinic
      visit prior to and following phacoemulsification. Results. We evaluated 158 eyes
      of 158 subjects; 15 (9.5%) had ODH noted at least once during the 2-year study
      period. Four eyes had ODH identified on postoperative day 1, for a cross
      sectional prevalence of 2.5%. Fourteen ODH episodes were noted preoperatively
      versus 12 episodes postoperatively (P = 0.68). Aspirin use was associated with
      ODH (P = 0.015). Conclusions. Our cross-sectional study found a prevalence of ODH
      immediately after CE that was similar to other published rates, and our
      longitudinal study did not find an increase in ODH in the year after
      phacoemulsification when compared to the year prior to surgery. 

PMID- 24729901
TI  - Hypersensitivity of vestibular system to sound and pseudoconductive hearing loss
      in deaf patients.
AB  - The objective of this cross-sectional study is to compare bone-conducted low
      frequency hearing thresholds (BClf) to cervical vestibular evoked myogenic
      potentials (cVEMPs) findings in prelingual adult deaf patients. The fifty
      participants (100 ears) included twenty healthy controls and thirty other
      subjects selected from patients who presented with bilateral prelingual deafness
      to Department of Audiology of Hamadan University of Medical Sciences and Health
      Services (Hamadan, Iran). Assessments comprised of audiological evaluations,
      cVEMPs, and computerized tomography scans. Twenty deaf patients (forty affected
      ears) with bilateral decreased vestibular excitability as detected by abnormal
      cVEMPs revealed that BClf hearing thresholds were completely absent. Ten deaf
      patients (twenty unaffected ears) with normal cVEMPs reported a sensation of the
      sound at BClf hearing thresholds (the mean for 250 Hz=41 dBHL and for 500
      Hz=57.75 dBHL). Multiple comparisons of mean p 13 latencies, mean n23 latencies
      and peak-to-peak amplitudes between three groups were significant (P = 0.01 for
      all, one-way ANOVA test). Multiple Comparisons of mean BClf between three groups
      were significant (P = 0.00, One-way ANOVA test). Conclusion. Hypersensitivity of
      vestibular system to sound augments BClf hearing thresholds in deaf patients. The
      sensation of the sound at low frequencies may be present in patients with total
      deafness and normal vestibular function (predominantly saccule). This improvement
      disappears when saccular function is lost. 

PMID- 24729900
TI  - Corneal biomechanical properties in different ocular conditions and new
      measurement techniques.
AB  - Several refractive and therapeutic treatments as well as several ocular or
      systemic diseases might induce changes in the mechanical resistance of the
      cornea. Furthermore, intraocular pressure measurement, one of the most used
      clinical tools, is also highly dependent on this characteristic. Corneal
      biomechanical properties can be measured now in the clinical setting with
      different instruments. In the present work, we review the potential role of the
      biomechanical properties of the cornea in different fields of ophthalmology and
      visual science in light of the definitions of the fundamental properties of
      matter and the results obtained from the different instruments available. The
      body of literature published so far provides an insight into how the corneal
      mechanical properties change in different sight-threatening ocular conditions and
      after different surgical procedures. The future in this field is very promising
      with several new technologies being applied to the analysis of the corneal
      biomechanical properties. 

PMID- 24729903
TI  - Prognostic value of mandard and dworak tumor regression grading in rectal cancer:
      study of a single tertiary center.
AB  - Goal. To evaluate the prognostic value of Mandard and Dworak grading systems
      regarding neoadjuvant chemoradiotherapy (CRT) response on rectal cancer.
      Materials and Methods. We queried our center's database for patients with colo
      rectal cancer with locally advanced rectal cancer (LARC) who received neoadjuvant
      CRT followed by total mesorectum excision (TME) between 2003 and 2011. After
      excluding 18 patients from the initial query the remaining 139 were reassessed
      for disease recurrence and survival; the specimens' slides were reviewed and
      classified according to two tumor regression grading (TRG) systems: Mandard and
      Dworak. Based on these TRG scores, two patient groups were created: patients with
      good response versus patients with bad response (Mandard TRG1+2 versus Mandard
      TRG3+4+5 and Dworak TRG4+3 versus Dworak TRG2+1+0). Overall survival (OS),
      disease-free survival (DFS), and disease recurrence were then evaluated. Results.
      Mean age was 64.2 years and median follow up was 56 months. No significant
      survival difference was found when comparing patients with Dworak TRG 4+3 versus
      Dworak TRG2+1+0 (P = 0.10). Mandard TRG1+2 presented with significantly better OS
      and DFS than Mandard TRG3+4+5 (OS P = 0.013; DFS P = 0.007). Conclusions. Mandard
      system provides higher accuracy over Dworak system in predicting rectal cancer
      prognosis when neoadjuvant CRT is applied for tumor regression. 

PMID- 24729904
TI  - Quantification of Protoporphyrin IX Accumulation in Glioblastoma Cells: A New
      Technique.
AB  - Introduction. 5-Aminolevulinic Acid (5-ALA) is a precursor of heme synthesis. A
      metabolite, protoporphyrin IX (PpIX), selectively accumulates in neoplastic
      tissue including glioblastoma. Presurgical administration of 5-ALA forms the
      basis of fluorescence-guided resection (FGR) of glioblastoma (GBM) tumors.
      However, not all gliomas accumulate sufficient quantities of PpIX to fluoresce,
      thus limiting the utility of FGR. We therefore developed an assay to determine
      cellular and pharmacological factors that impact PpIX fluorescence in GBM. This
      assay takes advantage of a GBM cell line engineered to express yellow fluorescent
      protein. Methods. The human GBM cell line U87MG was transfected with a YFP
      expression vector. After treatment with a series of 5-ALA doses, both PpIX and
      YFP fluorescence were measured. The ratio of PpIX to YFP fluorescence was
      calculated. Results. YFP fluorescence permitted the quantification of cell
      numbers and did not interfere with 5-ALA metabolism. The PpIX/YFP fluorescence
      ratio provided accurate relative PpIX levels, allowing for the assessment of PpIX
      accumulation in tissue. Conclusion. Constitutive YFP expression strongly
      correlates with cell number and permits PpIX quantification. Absolute PpIX
      fluorescence alone does not provide information regarding PpIX accumulation
      within the cells. Our research indicates that our PpIX/YFP ratio assay may be a
      promising model for in vitro 5-ALA testing and its interactions with other
      compounds during FGR surgery. 

PMID- 24729905
TI  - Randomized, controlled comparison of advanced hemostatic pads in hepatic surgical
      models.
AB  - Blood loss during hepatic surgery leads to poor patient outcomes. This study
      investigates the hemostatic efficacy of a novel sealing hemostatic pad
      (polyethylene glycol-coated collagen, PCC) and a fibrin sealant pad (fibrin
      thrombin coated collagen, FTC) in a leporine hepatic segmentectomy and a porcine
      hepatic abrasion model. A segmentectomy was used to compare hemostatic success
      and hematoma incidence in 20 rabbits (10/group). Hepatic abrasions were used to
      compare hemostatic success up to 10 min after application in six pigs (42
      lesions/group). In the segmentectomy model, PCC achieved 100% hemostatic success
      within 2 min (95% CI: 72.3% to 100%) and FTC achieved 80% hemostatic success
      within 3 min (49.0% to 94.3%). PCC had lower hematoma incidence at 15 min (0.0
      versus 11.1%) and 24 h (20.0 versus 66.7%). In the abrasion model, PCC provided
      superior hemostatic success at 3 (odds ratio: 24.8, 95% CI: 8.86 to 69.2, P <
      0.001), 5 (66.3, 28.5 to 153.9, P < 0.001), 7 (177.5, 64.4 to 489.1, P < 0.001),
      and 10 min (777.6, 148.2 to 4078, P < 0.001) leading to statistically significant
      less blood loss. The novel sealing hemostat provides faster and more sustained
      hemostasis than a fibrin sealant pad in a leporine hepatic segmentectomy and a
      porcine hepatic abrasion model of hepatic surgery. 

PMID- 24729902
TI  - Fibrin Sealant: The Only Approved Hemostat, Sealant, and Adhesive-a Laboratory
      and Clinical Perspective.
AB  - Background. Fibrin sealant became the first modern era material approved as a
      hemostat in the United States in 1998. It is the only agent presently approved as
      a hemostat, sealant, and adhesive by the Food and Drug Administration (FDA). The
      product is now supplied as patches in addition to the original liquid
      formulations. Both laboratory and clinical uses of fibrin sealant continue to
      grow. The new literature on this material also continues to proliferate rapidly
      (approximately 200 papers/year). Methods. An overview of current fibrin sealant
      products and their approved uses and a comprehensive PubMed based review of the
      recent literature (February 2012, through March 2013) on the laboratory and
      clinical use of fibrin sealant are provided. Product information is organized
      into sections based on a classification system for commercially available
      materials. Publications are presented in sections based on both laboratory
      research and clinical topics are listed in order of decreasing frequency.
      Results. Fibrin sealant remains useful hemostat, sealant, and adhesive. New
      formulations and applications continue to be developed. Conclusions. This agent
      remains clinically important with the recent introduction of new commercially
      available products. Fibrin sealant has multiple new uses that should result in
      further improvements in patient care. 

PMID- 24729906
TI  - Effect of the entorhinal cortex on ictal discharges in low-Mg2+-induced epileptic
      hippocampal slice models.
AB  - The hippocampus plays an important role in the genesis of mesial temporal lobe
      epilepsy, and the entorhinal cortex (EC) may affect the hippocampal network
      activity because of the heavy interconnection between them. However, the
      mechanism by which the EC affects the discharge patterns and the transmission
      mode of epileptiform discharges within the hippocampus needs further study. Here,
      multielectrode recording techniques were used to study the spatiotemporal
      characteristics of epileptiform discharges in adult mouse hippocampal slices and
      combined EC-hippocampal slices and determine whether and how the EC affects the
      hippocampal neuron discharge patterns. The results showed that low-Mg2+
      artificial cerebrospinal fluid induced interictal discharges in hippocampal
      slices, whereas, in combined EC-hippocampal slices the discharge pattern was
      alternated between interictal and ictal discharges, and ictal discharges
      initiated in the EC and propagated to the hippocampus. The pharmacological effect
      of the antiepileptic drug valproate (VPA) was tested. VPA reversibly suppressed
      the frequency of interictal discharges but did not change the initiation site and
      propagation speed, and it completely blocked ictal discharges. Our results
      suggested that EC was necessary for the hippocampal ictal discharges, and ictal
      discharges were more sensitive than interictal discharges in response to VPA.

PMID- 24729907
TI  - Manilkara zapota (Linn.) Seeds: A Potential Source of Natural Gum.
AB  - Mucilage isolated from seeds of Manilkara zapota (Linn.) P. Royen syn. is a plant
      growing naturally in the forests of India. This mucilage is yet to be
      commercially exploited, and characterized as polymer. Various physicochemical
      methods like particle size analysis, scanning electron microscopy, thermal
      analysis, gel permeation chromatography, X-ray diffraction spectrometry, zeta
      potential, Fourier transform infrared spectroscopy, and nuclear magnetic
      resonance spectroscopy have been employed to characterize this gum in the present
      study. Particle size analyses suggest that mucilage has particle size in
      nanometer. Scanning electron microscopy analysis suggests that the mucilage has
      irregular particle size. The glass transition temperature of the gum was observed
      to be 138 degrees C and 136 degrees C by differential scanning calorimetry and
      differential thermal analysis, respectively. The thermogravimetric analysis
      suggested that mucilage had good thermal stability. The average molecular weight
      of mucilage was determined to be 379180, by gel permeation chromatography, while
      the viscosity of mucilage was observed to be 219.1 cP. The X-ray diffraction
      spectrometry pattern of the mucilage indicates a completely amorphous structure.
      Elemental analysis of the gum revealed the contents of carbon, hydrogen,
      nitrogen, and sulfur to be 80.9 (%), 10.1 (%), 1.58 (%), and 512 (mg/kg),
      respectively. Mucilage had specific content of calcium, magnesium, potassium,
      lower concentrations of aluminum, cadmium, cobalt, lead, and nickel. The major
      functional groups identified from FT-IR spectrum include 3441 cm(-1) (-OH), 1660
      cm(-1) (Alkenyl C-H & C=C Stretch), 1632 cm(-1) (-COO-), 1414 cm(-1) (-COO-), and
      1219 cm(-1) (-CH3CO). Analysis of mucilage by paper chromatography and 1D NMR,
      indicated the presence of rhamnose, xylose, arabinose, mannose, and fructose. 

PMID- 24729908
TI  - Influence of Stress Connected with Moving to a New Farm on Potentially MAP
      Infected Mouflons.
AB  - There is no European legislation concerning paratuberculosis that requires that
      imported animals be kept in quarantine and commonly they are directly released
      into areas with other animals. In this study, detection of latent infection of
      paratuberculosis in healthy mouflons previously diagnosed as paratuberculosis
      free, but originating from a real time quantitative PCR- (qPCR-) positive herd,
      occurred after their transport to a new farm. During a twelve-day quarantine
      period, all mouflons irregularly shed Mycobacterium avium subsp. paratuberculosis
      (MAP) in faeces, and in a small number of cases also in milk. After the animals
      were released from quarantine, MAP was detected for a further two days, after
      which, testing was negative, except in one case. Therefore, the stress connected
      with transport, novel environment, dietary change, or limited area with high
      density of animals might have contributed to the induction of paratuberculosis
      and the shedding of MAP from the animals, previously diagnosed as MAP-negative.
      According to these results, the keeping of imported animals in quarantine and
      their examination for MAP presence not only before the transport but also
      afterwards should be recommended. The designation of a particular area of a farm
      as a quarantine enclosure could help to mitigate the impact of stress caused by a
      confined space with a high density of animals. 

PMID- 24729910
TI  - Trends in antiparkinsonian medication use in new zealand: 1995-2011.
AB  - Prescribing trends for medications are influenced by development of new drugs,
      changes in knowledge about efficacy and side effects, and priorities set by
      funding agencies. Changes in the utilization of antiparkinsonian agents in the
      outpatient community in New Zealand were investigated by using the national
      prescription database for the period 1995-2011. The dispensed volumes of
      antiparkinsonian agents were converted into number of defined daily doses per
      1000 inhabitants per day for analysis. Increases in the dispensed volumes of
      levodopa (77%), amantadine (350%), and catechol-o-methyl transferase inhibitors
      (326%) occurred during the study period. Conversely, decreases in the dispensed
      volumes of anticholinergics (48%), selegiline (82%), and dopamine agonists (6.2%)
      were observed. New Zealand has seen a substantial increase of the amount of
      levodopa dispensed in the past 17 years. This increase appears to be related to
      an increase in the number of people taking the medication. We are unable to
      extrapolate this change to an increase in the prevalence of PD, given levodopa is
      used in the treatment of a number of medical conditions. The changes in other
      antiparkinsonian medications largely reflect changes in availability (increases
      in entacapone and ropinirole) and best practice treatment (declines in
      anticholinergics, selegiline, and tolcapone). 

PMID- 24729909
TI  - Metabotropic glutamate receptor 5 negative modulation in phase I clinical trial:
      potential impact of circadian rhythm on the neuropsychiatric adverse reactions-do
      hallucinations matter?
AB  - Metabotropic Glutamate Receptor 5 (mGluR5) negative allosteric modulators (NAMs)
      may play a role in some psychiatric disorders such as anxiety and depression. The
      pharmacokinetic profile and pharmacodynamics effects of mGluR5-NAMs have been
      previously reported. We performed a post hoc analysis of pharmacological and
      clinical data obtained from 18 young healthy female subjects who received a
      mGluR5-NAM in the context of a phase I drug-drug interaction study between a
      mGluR5 NAM and a monophasic oral contraceptive. mGluR5-NAM was administered in an
      escalating bidaily dose level design. There was no interaction between the OC and
      mGluR5-NAM. Higher morning mGluR5-NAM plasma concentrations were found compared
      to evening concentrations. Most of the observed clinically significant
      neuropsychiatric adverse reactions occurred nocturnally and included visual
      (pseudo) hallucinations, insomnia accompanied by secondary behavioural disorders,
      and cognitive dysfunction symptoms of sufficient severity to interfere with daily
      functioning. Circadian rhythm-related physiological variations in drug absorption
      and disposition may explain this pharmacokinetics-pharmacodynamics apparently
      disproportionate relationship. We suggest that clinical trials evaluating basic
      pharmacokinetic properties of psychiatric medications consider potential drug's
      chronopharmacokinetics. This may assist with dose optimization and minimize
      serious neuropsychiatric adverse reactions in the vulnerable psychiatric patient.

PMID- 24729911
TI  - Five Years of Acute Stroke Unit Care: Comparing ASU and Non-ASU Admissions and
      Allied Health Involvement.
AB  - Background. Evidence indicates that Stroke Units decrease mortality and
      morbidity. An Acute Stroke Unit (ASU) provides specialised, hyperacute care and
      thrombolysis. John Hunter Hospital, Australia, admits 500 stroke patients each
      year and has a 4-bed ASU. Aims. This study investigated hospital admissions over
      a 5-year period of all strokes patients and of all patients admitted to the 4-bed
      ASU and the involvement of allied health professionals. Methods. The study
      retrospectively audited 5-year data from all stroke patients admitted to John
      Hunter Hospital (n = 2525) and from nonstroke patients admitted to the ASU (n =
      826). The study's primary outcomes were admission rates, length of stay (days),
      and allied health involvement. Results. Over 5 years, 47% of stroke patients were
      admitted to the ASU. More male stroke patients were admitted to the ASU (chi(2) =
      5.81; P = 0.016). There was a trend over time towards parity between the number
      of stroke and nonstroke patients admitted to the ASU. When compared to those
      admitted elsewhere, ASU stroke patients had a longer length of stay (z = -8.233;
      P = 0.0000) and were more likely to receive allied healthcare. Conclusion. This
      is the first study to report 5 years of ASU admissions. Acute Stroke Units may
      benefit from a review of the healthcare provided to all stroke patients. The
      trends over time with respect to the utilisation of the John Hunter Hospitall's
      ASU have resulted in a review of the hospitall's Stroke Unit and allied
      healthcare. 

PMID- 24729912
TI  - Inhibition of Protein kinase Mzeta (PKMzeta) in the mesolimbic system alters
      cocaine sensitization in rats.
AB  - Chronic cocaine use produces long-lasting changes in reward circuits that may
      underlie the transition from casual to compulsive patterns of drug use. Although
      strong neuroadaptations within the mesocorticolimbic system are known to occur,
      the specific role of these drug-induced plasticities on sensitization remains to
      be elucidated. Here we investigate whether PKMzeta, a protein involved in
      maintaining long-term potentiation (LTP), plays a role in these cocaine-induced
      changes in synaptic strengthening. We performed whole-cell voltage clamp
      recordings of putative ventral tegmental area (VTA) dopamine (DA) cells 24 hours
      after five days of 15 mg/kg i.p. cocaine or isovolumetric saline injections. We
      observed that superfusion of 5uM ZIP (PKMzeta inhibitory peptide) decreased AMPA
      currents and AMPA/NMDA ratios only in cocaine sensitized rats. In vivo ZIP
      microinfusions (10 nmol) into the VTA after cocaine sensitization decreased
      locomotor activity on a subsequent cocaine challenge only if given ZIP is given
      before the withdrawal period. On the other hand, ZIP microinfusions into the
      nucleus accumbens (NAc) core after a seven days withdrawal period disrupt the
      expression of locomotor sensitization. The present data provide a potentially
      relevant region, and time-specific PKMzeta-dependent brain mechanism that enables
      sensitization. Our results support the vision that addiction involves a
      pathological learning process. They imply that if this synaptic strengthening is
      reversed, changes in the behavioral response may also be overturned.

PMID- 24729913
TI  - Between Amyloids and Aggregation Lies a Connection with Strength and Adhesion.
AB  - We tell of a journey that led to discovery of amyloids formed by yeast cell
      adhesins and their importance in biofilms and host immunity. We begin with the
      identification of the adhesin functional amyloid-forming sequences that mediate
      fiber formation in vitro. Atomic force microscopy and confocal microscopy show 2
      dimensional amyloid "nanodomains" on the surface of cells that are activated for
      adhesion. These nanodomains are arrays of adhesin molecules that bind multivalent
      ligands with high avidity. Nanodomains form when adhesin molecules are stretched
      in the AFM or under laminar flow. Treatment with antiamyloid perturbants or
      mutation of the amyloid sequence prevents adhesion nanodomain formation and
      activation. We are now discovering biological consequences. Adhesin nanodomains
      promote formation and maintenance of biofilms, which are microbial communities.
      Also, in abscesses within candidiasis patients, we find adhesin amyloids on the
      surface of the fungi. In both human infection and a Caenorhabditis elegans
      infection model, the presence of fungal surface amyloids elicits anti
      inflammatory responses. Thus, this is a story of how fungal adhesins respond to
      extension forces through formation of cell surface amyloid nanodomains, with key
      consequences for biofilm formation and host responses.

PMID- 24729915
TI  - Study on dicarboxylic acids in aerosol samples with capillary electrophoresis.
AB  - The research was performed to study the simultaneous detection of a homologous
      series of alpha , omega -dicarboxylic acids (C2-C10), oxalic, malonic, succinic,
      glutaric, adipic, pimelic, suberic, azelaic, and sebacic acids, with capillary
      electrophoresis using indirect UV detection. Good separation efficiency in 2,6
      pyridinedicarboxylic acid as background electrolyte modified with myristyl
      trimethyl ammonium bromide was obtained. The dicarboxylic acids were ionised and
      separated within five minutes. For the study, authentic samples were collected
      onto dry cellulose membrane filters of a cascade impactor (12 stages) from
      outdoor spring aerosols in an urban area. Hot water and ultrasonication
      extraction methods were used to isolate the acids from membrane filters. Due to
      the low concentrations of acids in the aerosols, the extracts were concentrated
      with solid-phase extraction (SPE) before determination. The enrichment of the
      carboxylic acids was between 86 and 134% with sample pretreatment followed by 100
      time increase by preparation of the sample to 50  MU L. Inaccuracy was optimised
      for all the sample processing steps. The aerosols contained dicarboxylic acids C2
      C10. Then, mostly they contained C2, C5, and C10. Only one sample contained
      succinic acid. In the study, the concentrations of the acids in aerosols were
      lower than 10 ng/m(3). 

PMID- 24729914
TI  - The Value of Admission Serum IL-8 Monitoring and the Correlation with IL-8 (
      251A/T) Polymorphism in Critically Ill Patients.
AB  - Background. The clinical management of sepsis is a highly complicated process.
      Disruption of the immune system explains in part the major variation in sepsis
      outcome. IL-8 is a proinflammatory cytokine, genetic polymorphism of this
      cytokine could explain the outcome of sepsis. The present study was conducted to
      determine the value of serum IL-8 monitoring and its (-251A/T) genetic
      polymorphism in critically ill patients. Patients and Methods. 180 critically ill
      patients were allocated into two groups, 90 septic patients (sepsis group) and 90
      nonseptic patients (SIRS group). Admission serum IL-8 and its (-251A/T) mutant
      allele were detected. Results. The admission mean value of serum IL-8 was
      significantly elevated in sepsis group. In both groups, the mean value of serum
      IL-8 in nonsurvived patients and patients with IL-8 (-251A/T) mutant allele was
      significantly higher. A positive correlation of survival and IL-8 (-251A/T)
      mutant allele was detected in both groups. The serum IL-8 distinguished wild from
      IL-8 (-251A/T) mutant allele at a cut-off value of 600 pg/mL. Conclusion. The
      admission mean value of serum IL-8 was significantly elevated in septic,
      nonsurvived, and patients with IL-8 (-251A/T) mutant alleles. A positive
      correlation of survival and IL-8 (-251A/T) mutant allele patients was detected. 

PMID- 24729916
TI  - Simultaneous determination of cortisol and cortisone from human serum by liquid
      chromatography-tandem mass spectrometry.
AB  - A fast, sensitive, and selective liquid chromatography-tandem mass spectrometry
      (LC-MS/MS) method was validated and then the levels of cortisol and cortisone
      from sera of healthy adults were determined by the LC-MS/MS method. One hundred
      MU L of serum sample was directly extracted by adding 2 mL ethyl acetate,
      followed by chromatographic separation on a C18 column with a mobile phase
      consisting of 5 mM ammonium acetate and methanol (25 : 75, v/v). The precision,
      accuracy, and average recovery of the method were 1.5-5.3%, 95.4-102.5%, and
      96.4% for cortisol, and 1.9-6.0%, 89.2-98.8%, and 79.9% for cortisone,
      respectively. The method was linear from 1.0 to 500.0 ng/mL (r(2) = 0.999) for
      cortisol and 2.5 to 100.0 ng/mL (r(2) = 0.998) for cortisone. The limits of
      detection (LOD) and quantification (LOQ) were 0.2 and 1.0 ng/mL for cortisol, and
      1.0 and 2.5 ng/mL for cortisone, respectively. The average cortisol concentration
      (133.9 +/- 63.7 ng/mL) of samples collected between 9:00 and 11:00 a.m. was
      higher approximately 4.4 times than that of cortisone (30.5 +/- 10.7 ng/mL) (P <
      0.0001). The average cortisone/cortisol ratio was 0.225. Therefore, the LC-MS/MS
      method may be useful for the diagnosis of some adrenal diseases and the
      assessment of 11 beta -hydroxysteroid dehydrogenase (11 beta -HSD) activity in
      clinical laboratories. 

PMID- 24729917
TI  - Preparation and characterization of an amphipathic magnetic nanosphere.
AB  - The amphipathic magnetic nanospheres were synthesized using C8 and polyethylene
      glycol as ligands. Their morphology, structure, and composition were
      characterized by transmission electron microscope, Fourier transform infrared,
      and elementary analysis. The prepared materials presented uniform sphere with
      size distribution about 200 nm. The magnetic characteristics of magnetic
      nanomaterials were measured by vibrating sample magnetometer. The target products
      had a saturation magnetization value of 50 emu g(-1) and superparamagnetism. The
      adsorption capability was also studied by static tests, and the material was
      applied to enrich benzenesulfonamide from calf serum. The results exhibited that
      the C8-PEG phase owned better adsorption capability, biocompatible property, and
      dispersivity in aqueous samples. 

PMID- 24729918
TI  - Gender Differences in Pulmonary Function, Respiratory Symptoms, and Macrophage
      Proteomics among HIV-Infected Smokers.
AB  - Background. HIV-infected subjects have an increased incidence of pulmonary
      emphysema. There are known gender differences in COPD phenotypic expression and
      diagnosis, but this is not well characterized in lung disease related to HIV. We
      analyzed a group at risk for the development of COPD (HIV-infected smokers) to
      determine gender differences in pulmonary symptoms, pulmonary function tests, and
      HRCT appearances. Methods. This was a cross-sectional, baseline analysis of a
      prospective study performed between 2006 and 2010. We performed symptomatic,
      pulmonary function, and computed tomography assessments in 243 HIV-infected
      smokers. In a subset bronchoalveolar lavage was performed with proteomic analysis
      of their alveolar macrophages. Results. The majority of the participants were
      male 213 (87.6%). There was significantly higher percentage of cough and phlegm
      production in males. There was also a lower FEV1 and a higher RV in males than
      females. Proteomic analysis revealed 29 proteins with at least a 2-fold higher
      expression in males and 13 identified proteins that were higher in females.
      Conclusions. In this group of HIV-infected smokers, airway symptoms and pulmonary
      function test abnormalities were higher in men than women. These gender
      differences may be due to differential expression of certain proteins in this
      group. 

PMID- 24729919
TI  - The Syndromic versus Laboratory Diagnosis of Sexually Transmitted Infections in
      Resource-Limited Settings.
AB  - Sexually transmitted infections (STIs) are highly prevalent in sub-Saharan
      Africa, where there is a severe HIV epidemic. Thus, accurate recognition and
      diagnosis of STIs are essential for successful HIV prevention programs in the
      region. Due to lack of trained personnel and adequate laboratory infrastructure
      in the region, information regarding the profile of STIs relies essentially on
      self-reported or physician-diagnosed symptoms. The main objective of the study
      was to assess the effectiveness of the syndromic diagnosis of STIs, which is
      often used as a proxy for laboratory diagnosis of STIs in sub-Saharan Africa and
      other resource-limited settings. The study builds on previously collected data
      from a community-based survey in Northern Tanzania. We found no significant
      agreements between patient-reported STIs symptoms and laboratory-confirmed STIs
      tests. The reported STIs symptoms had high specificity (range = 85-99%) and poor
      sensitivity (range = 2-17%). Knowledge gained from our study will have
      significant public health implications, and can help improve the syndromic
      diagnosis of STIs. 

PMID- 24729920
TI  - Let's Pay Attention to the Average.

PMID- 24729921
TI  - How far has the international neurourology journal progressed since its
      transformation into an english language journal?
AB  - PURPOSE: The publisher of the International Neurourology Journal changed the text
      to English in 2010 to promote the journal as an international publication. Four
      years later, what has happened to this journal? This paper will use citation
      indicators to describe the degree of internationalization. METHODS: Citation
      indicators such as impact factors, total citations from Web of Science, Science
      Journal Rankings (SJR), cites per documents (2 years), and Hirsch indexes (h
      indexes) from Web of Science, digital object identifier (DOI)/CrossRef,
      ScimagoJR, or Scopus were calculated. In addition, the native countries of the
      authors and researchers citing the journal in Web of Science were analyzed.
      RESULTS: Impact factors in 2012 and 2013 were 0.645 and 0.857, respectively.
      Total citations in 2011, 2012, and 2013 from Web of Science were 15, 51, and 99,
      respectively, and the SJRs in 2011 and 2012 were 0.220 and 0.390, respectively.
      The h-indexes from DOI/CrossRef, Scopus, and Web of Science were 7, 8, and 6,
      respectively. Out of 153 unsolicited published papers, 27 (17.6%) were from
      outside of Korea. The researchers citing the journal in Web of Science and Scopus
      were primarily from the United States, Korea, China, the United Kingdom, and
      France. Funding agencies supported 39 of 101 original articles (38.6%).
      CONCLUSIONS: After changing the text to the English language, the citation
      indicators show that the International Neurourology Journal has been elevated to
      an international journal. Although the nationality of authors varies from year to
      year, the increase in the number of manuscripts from international authors is
      obvious.

PMID- 24729922
TI  - Toll-like receptor 10-1-6 gene cluster polymorphisms are not associated with
      benign prostatic hyperplasia in korean population.
AB  - PURPOSE: Inflammation and infection have been associated with the pathogenesis of
      benign prostatic hyperplasia (BPH). Toll-like receptors (TLRs) play key roles in
      the innate immune system and initiate the inflammatory response to foreign
      pathogens. We investigated the relationship between TLR10-1-6 gene cluster
      polymorphisms and BPH. METHODS: We genotyped four promoter single nucleotide
      polymorphisms (SNPs) (TLR10, rs10004195; TLR1, rs5743557; and TLR6, rs1039560 and
      rs1039559) by directly sequencing (233 BPH patients and 214 control subjects).
      SNPStats and Haploview version 4.02 were used to analyze the data. Multiple
      logistic regression models (log-additive, dominant, and recessive) were performed
      to determine odds ratios (ORs), 95% confidence intervals (CIs), and P-values.
      RESULTS: The genotype and allele frequencies of each SNP was not different
      between the BPH and control groups (P>0.05). Haplotype analysis showed no
      association between the haplotype in the linkage disequilibrium (LD) block and
      BPH (P>0.05), although the LD block was constructed. CONCLUSIONS: These results
      indicate that the TLR10-1-6 gene cluster may be not associated with the
      development of BPH in the Korean population.

PMID- 24729923
TI  - Treadmill exercise ameliorates short-term memory disturbance in scopolamine
      induced amnesia rats.
AB  - PURPOSE: Scopolamine is a nonselective muscarinic cholinergic receptor
      antagonist, which induces impairment of learning ability and memory function.
      Exercise is known to ameliorate brain disturbance induced by brain injuries. In
      the present study, we investigated the effect of treadmill exercise on short-term
      memory in relation to acetylcholinesterase (AChE) expression in the hippocampus,
      using a scopolamine-induced amnesia model in mice. METHODS: To induce amnesia, 1
      mg/kg scopolamine hydrobromide was administered intraperitoneally once per day
      for 14 days. A step-down avoidance test for short-term memory was conducted. AChE
      histochemistry, immunohistochemistry for collagen IV, and doublecortin were
      performed. RESULTS: Short-term memory deteriorated in the mice with scopolamine
      induced amnesia, concomitant with enhanced AChE expression and suppression of
      angiogenesis in the hippocampus. Critically, treadmill exercise ameliorated short
      term memory impairment, suppressed AChE expression, and enhanced angiogenesis in
      the mice with scopolamine-induced amnesia. CONCLUSIONS: Overexpression of AChE is
      implicated in both brain and renal disease. The findings of our study indicate
      that treadmill exercise may be of therapeutic value in neurodegenerative and
      renal diseases by suppressing the effects of AChE expression.

PMID- 24729924
TI  - Clinical factors associated with dose escalation of solifenacin for the treatment
      of overactive bladder in real life practice.
AB  - PURPOSE: To determine the baseline clinical characteristics associated with dose
      escalation of solifenacin in patients with overactive bladder (OAB). METHODS: We
      analyzed the data of patients with OAB (micturition frequency >=8/day and urgency
      >=1/day) who were treated with solifenacin and followed up for 24 weeks.
      According to our department protocol, all the patients kept voiding diaries, and
      OAB symptom scores (OABSS) were monitored at baseline and after 4, 12, and 24
      weeks of solifenacin treatment. RESULTS: In total, 68 patients (mean age, 60.8+/
      10.0 years) were recruited. The dose escalation rate by the end of the study was
      41.2%, from 23.5% at 4 weeks and 17.6% at 12 weeks. At baseline, the dose
      escalator group had significantly more OAB wet patients (53.6% vs. 20.0%) and
      higher total OABSS (10.2+/-2.4 vs. 7.9+/-3.5, P=0.032) than the nonescalator
      group. OAB wet (odds ratio [OR], 4.615; 95% confidence interval [CI], 1.578
      13.499; P<0.05) and total OABSS (OR, 1.398; 95% CI, 1.046-1.869; P<0.05) were
      found to be independently associated with dose escalation. CONCLUSIONS: Patients
      who have urgency urinary incontinence and high total OABSS have a tendency for
      dose escalation of solifenacin.

PMID- 24729925
TI  - Prevalence, Risk Factors, Quality of Life, and Health-Care Seeking Behaviors of
      Female Urinary Incontinence: Results From the 4th Korean National Health and
      Nutrition Examination Survey VI (2007-2009).
AB  - PURPOSE: There is a lack of information on female urinary incontinence (UI) in
      South Korea. We investigated the prevalence, risk factors, quality of life (QoL),
      and healthcare-seeking behaviors of women with UI. METHODS: We included 9,873
      women over the age of 20 years who had participated in the Korea National Health
      and Nutrition Examination Survey IV. The condition of UI was defined as answering
      "yes" to the question "Do you have UI?" Additionally, health care seeking
      behavior for UI was defined as answering "yes" to "Have you ever been treated for
      UI?' The EuroQoL-5 Dimension (EQ-5D) descriptive system was used to evaluate QoL.
      RESULTS: The mean age of our sample was 49.7 years. The overall prevalence of UI
      was 7.9%. The prevalence of UI significantly increased with age. The rate of
      healthcare-seeking behavior for UI also significantly increased with age.
      However, the rate of healthcare seeking for UI was significantly lower when
      compared to the prevalence of UI. In our multivariate analysis, age, body mass
      index, and marriage were significantly and independently associated with UI. As
      the severity of all the subscales of EQ-5D increased, the unadjusted odds ratio
      for UI also increased. After adjusting for potential confounders, the subscales
      of mobility, usual activities, pain/discomfort, and anxiety/depression from the
      EQ-5D were significantly associated with UI. CONCLUSIONS: UI is a common disease
      and is significantly associated with QoL. Our results suggest the need for
      developing preventive measures and treatment policies for UI.

PMID- 24729926
TI  - Correlation between the visual prostate symptom score and international prostate
      symptom score in patients with lower urinary tract symptoms.
AB  - PURPOSE: To evaluate the correlation between the Visual Prostate Symptom Score
      (VPSS) and International Prostate Symptom Score (IPSS). METHODS: We enrolled 240
      new male patients who had visited National Police Hospital more than twice during
      a 6-month period starting from July 2013. At initial visit, the Korean version of
      the IPSS and VPSS, uroflowmetry, and transrectal ultrasonography were used to
      evaluate urinary symptoms. After medication, IPSS and VPSS questionnaires were
      issued again. The Spearman correlation test and the Mantel-Haenszel test were
      used to evaluate the relationship between the IPSS and VPSS. RESULTS: The median
      age, total prostate volume, total IPSS, and total VPSS were 59.0 years, 28.0 mL,
      12, and 9, respectively. Total VPSS, VPSS obstructive symptoms, VPSS irritative
      symptoms, and VPSS quality of life (QoL) significantly correlated with the total
      IPSS, IPSS obstructive symptoms, IPSS irritative symptoms, and IPSS QoL,
      respectively (correlation coefficient, P-value: 0.632, <0.001; 0.431, <0.001;
      0.696, <0.001; and 0.799, <0.001; respectively). The change in the total IPSS
      after treatment also significantly correlated with the change in total VPSS after
      treatment (correlation coefficient, P-value: 0.364, <0.001). There were
      significant correlations between maximal flow rate and IPSS/VPSS obstructive
      symptoms (correlation coefficient, P-value: -0.190, 0.004; -0.269, <0.001,
      respectively). Additionally, there was a significant increase in the ratio of the
      maximal flow rate <15 mL/sec to VPSS obstructive symptoms as the severity of the
      VPSS obstructive symptoms increased (P trend <0.001). CONCLUSIONS: VPSS might be
      useful in evaluating lower urinary tract symptoms at the initial visit and
      assessing these symptoms at longitudinal follow-up examinations.

PMID- 24729927
TI  - Female urethral condyloma causing bladder outlet obstruction.
AB  - In women, urethral condyloma rarely leads to a bladder outlet obstruction. A 39
      year-old woman who presented with frequency, urgency, and residual urine
      sensation was found to have a condyloma in her urethral meatus. Urodynamic study
      indicated bladder outlet obstruction. After condyloma excision, she returned to
      normal voiding, and the free maximum flow rate improved. In women, excision of
      urethral condylomas that cause obstruction can be an effective treatment with
      early recovery of voiding function. 

PMID- 24729928
TI  - Neurologic complications of percutaneus nephrolithotomy.

PMID- 24729929
TI  - Inclusion of South African adolescents in HIV vaccine trials.
AB  - South Africa has more people living with HIV than any other nation. The HIV
      epidemic in South Africa is being driven by new infections among adolescents.
      Inclusion of adolescents in HIV vaccine trials is essential for successful
      vaccine development, however, recruitment and retention of at-risk South African
      adolescents into these trials poses a number of legal, ethical and operational
      challenges. This article discusses the South African ethico-legal context in
      which future adolescent HIV vaccine trials would be conducted followed by a
      review of available data regarding strategies for recruitment into these trials
      and retention of trial participants.

PMID- 24729931
TI  - Focusing on Cause or Cure?: Priorities and Stakeholder Presence in Childhood
      Psychiatry Research.
AB  - BACKGROUND: Biomedical research is influenced by many factors, including the
      involvement of stakeholder groups invested in research outcomes. Stakeholder
      involvement in research efforts raise questions of justice as their specific
      interests and motivations play a role in directing research resources that
      ultimately produce knowledge shaping how different conditions (and affected
      individuals) are understood and treated by society. This issue is highly relevant
      to child psychiatry research where diagnostic criteria and treatment strategies
      are often controversial. Biological similarities and stakeholder differences
      between attention deficit hyperactivity disorder (ADHD) and autism spectrum
      disorder (ASD) provide an opportunity to explore this issue by comparing research
      foci and stakeholder involvement in these conditions. METHODS: A subset of ADHD
      and ASD research articles published between 1970-2010 were randomly selected from
      the PubMed database and coded for research focus, funding source(s), and author
      reported conflicts of interest (COIs). Chi-square analyses were performed to
      identify differences between and within ADHD and ASD research across time.
      RESULTS: The proportion of ADHD research dedicated to basic, description, and
      treatment research was roughly similar and remained stable over time, while ASD
      research showed a significant increase in basic research over the past decade.
      Government was the primary research funder for both conditions, but for-profit
      funders were a notable presence in ADHD research, while joint-funding efforts
      between non-profit and government funders were a notable presence in ASD
      research. Lastly, COIs were noted more frequently in ADHD than in ASD research.
      CONCLUSIONS: Our study shows significant differences in research foci and funding
      sources between the conditions, and identifies the specific involvement of for
      profit and non-profit groups in ADHD and ASD, respectively. Our findings
      highlight the relationship between stakeholders outside the research community
      and research trajectories and suggest that examinations of these relationships
      must be included in broader considerations of biomedical research ethics.

PMID- 24729932
TI  - Inhibition of Epithelial-to-Mesenchymal Transition (EMT) in Cancer by Nitric
      Oxide: Pivotal Roles of Nitrosylation of NF-kappaB, YY1 and Snail.
AB  - Treatment of cancer cell lines with high levels of nitric oxide (NO) via NO
      donors, such as DETANONOate, inhibits cell growth and survival pathways and
      sensitizes resistant tumor cells to apoptosis by chemoimmunotherapeutic drugs. In
      addition, we recently have reported that NO also inhibits the epithelial-to
      mesenchymal transition (EMT) phenotype in metastatic cancer cell lines via
      dysregulation of the nuclear factor (NF)-kappaB/Snail/Yin Yang 1 (YY1)/Raf kinase
      inhibitor protein circuitry. The mechanism underlying NO-mediated dysregulation
      of this circuit was investigated, namely, NO-mediated inhibition of the activity
      of the transcription factors NF-kappaB, Snail, and YY1. We hypothesized that one
      mechanism of NO-mediated inhibition may invoke the NO-induced S-nitrosylation of
      these transcription factors. We demonstrate in metastatic and EMT+ human prostate
      carcinoma cell lines that treatment with NO results in the S-nitrosylation of NF
      kappaB (p50), Snail, and YY1 and inhibits their activities, resulting in the
      reversal of the EMT phenotype into a mesenchymal-to-epithelial transition
      phenotype. These findings suggest that NO donors may be potential therapeutic
      agents in both the reversal of resistance and the inhibition of EMT and
      metastasis.

PMID- 24729930
TI  - Clinical update for the diagnosis and treatment of Clostridium difficile
      infection.
AB  - Clostridium difficile infection (CDI) presents a rapidly evolving challenge in
      the battle against hospital-acquired infections. Recent advances in CDI diagnosis
      and management include rapid changes in diagnostic approach with the introduction
      of newer tests, such as detection of glutamate dehydrogenase in stool and
      polymerase chain reaction to detect the gene for toxin production, which will
      soon revolutionize the diagnostic approach to CDI. New medications and multiple
      medical society guidelines have introduced changing concepts in the definitions
      of severity of CDI and the choice of therapeutic agents, while rapid expansion of
      data on the efficacy of fecal microbiota transplantation heralds a revolutionary
      change in the management of patients suffering multiple relapses of CDI. Through
      a comprehensive review of current medical literature, this article aims to offer
      an intensive review of the current state of CDI diagnosis, discuss the strengths
      and limitations of available laboratory tests, compare both current and future
      treatments options and offer recommendations for best practice strategies.

PMID- 24729933
TI  - Susceptibility to focal and global brain ischemia of Alzheimer mice displaying
      abeta deposits: effect of immunoglobulin.
AB  - Cerebral ischemia is a risk factor for Alzheimer's disease (AD). Moreover, recent
      evidence indicates that it is a two-way street as the incidence rate of stroke is
      significantly higher in AD patients than those without the disease. Here we
      investigated the interaction of ischemic brain insults and AD in 9-month-old
      ApdE9 mice, which show full-blown accumulation of Abeta deposits and microgliosis
      in the brain. Permanent occlusion of the middle cerebral artery (pMCAo) resulted
      in 36% larger infarct in ApdE9 mice compared to their wild-type (wt) controls.
      This was not due to differences in endothelium-dependent vascular reactivity.
      Treatment with human intravenous immunoglobulin (IVIG) reduced the infarct
      volumes and abolished the increased vulnerability of ApdE9 mice to pMCAo induced
      brain ischemia. When the mice were exposed to global brain ischemia (GI), an
      insult of hippocampal cells, ApdE9 mice showed increased neuronal loss in CA2 and
      CA3 subregions compared to their wt controls. GI was associated with increased
      microgliosis, astrogliosis, infiltration of blood-derived monocytic cells, and
      neurogenesis without clear differences between the genotypes. IVIG treatment
      prevented the GI-induced neuron loss in hippocampal CA1 and CA3 regions in ApdE9
      mice. IVIG treatment increased microgliosis in wt but not in ApdE9 mice. Finally,
      GI induced 60% reduction in the hippocampal Abeta burden in ApdE9 mice, which was
      not affected by IVIG treatment. The results indicate that the AD pathology with
      Abeta deposits and microgliosis increases ischemic vulnerability in various brain
      areas. Moreover, IVIG treatment may be beneficial especially in patients
      suffering from both acute ischemic insult and AD. 

PMID- 24729934
TI  - Resveratrol Suppresses Expression of VEGF by Human Retinal Pigment Epithelial
      Cells: Potential Nutraceutical for Age-related Macular Degeneration.
AB  - Age-related macular degeneration (AMD) is a sight threating retinal eye disease
      that affects millions of aging individuals world-wide. Choroid-retinal pigment
      epithelium (RPE)-neuroretina axis in the posterior compartment of the eye is the
      primary site of AMD pathology. There are compelling evidence to indicate
      association of vascular endothelial growth factors (VEGF) to AMD. Here, we report
      the inhibitory actions of resveratrol (RSV) on inflammatory cytokine, TGF-beta
      and hypoxia induced VEGF secretion by human retinal pigment epithelial cells
      (HRPE). HRPE cultures prepared from aged human donor eyes were used for the
      studies in this report. HRPE secreted both VEGF-A and VEGF-C in small quantities
      constitutively. Stimulation with a mixture of inflammatory cytokines (IFN-gamma,
      TNF-alpha, IL-1beta), significantly increased the secretion of both VEGF-A and
      VEGF-C. RSV, in a dose dependent (10-50 uM) manner, suppressed VEGF-A and VEGF-C
      secretion induced by inflammatory cytokines significantly. RT-PCR analysis
      indicated that effects of RSV on VEGF secretion were possibly due to decreased
      mRNA levels. TGF-beta and cobalt chloride (hypoxia mimic) also upregulated HRPE
      cell production of VEGF-A, and this was inhibited by RSV. In contrast, RSV had no
      effect on anti-angiogenic molecules, endostatin and pigment epithelial derived
      factor secretion. Studies using an in vitro scratch assay revealed that wound
      closure was also inhibited by RSV. These results demonstrate that RSV can
      suppress VEGF secretion induced by inflammatory cytokines, TGF-beta and hypoxia.
      Under pathological conditions, over expression of VEGF is known to worsen AMD.
      Therefore, RSV may be useful as nutraceutical in controlling pathological
      choroidal neovascularization processes in AMD. 

PMID- 24729935
TI  - Aging and injury: alterations in cellular energetics and organ function.
AB  - Aging is characterized by increased oxidative stress, heightened inflammatory
      response, accelerated cellular senescence and progressive organ dysfunction. The
      homeostatic imbalance with aging significantly alters cellular responses to
      injury. Though it is unclear whether cellular energetic imbalance is a cause or
      effect of the aging process, preservation of mitochondrial function has been
      reported to be important in organ function restoration following severe injury.
      Unintentional injuries are ranked among the top 10 causes of death in adults of
      both sexes, 65 years and older. Aging associated decline in mitochondrial
      function has been shown to enhance the vulnerability of heart, lung, liver and
      kidney to ischemia/reperfusion injury. Studies have identified alterations in the
      level or activity of factors such as SIRT1, PGC-1alpha, HIF-1alpha and c-MYC
      involved in key regulatory processes in the maintenance of mitochondrial
      structural integrity, biogenesis and function. Studies using experimental models
      of hemorrhagic injury and burn have demonstrated significant influence of aging
      in metabolic regulation and organ function. Understanding the age-associated
      molecular mechanisms regulating mitochondrial dysfunction following injury is
      important towards identifying novel targets and therapeutic strategies to improve
      the outcome after injury in the elderly. 

PMID- 24729936
TI  - Hemodynamic Aging as the Consequence of Structural Changes Associated with Early
      Vascular Aging (EVA).
AB  - An increase in peripheral vascular resistance at rest is not routinely observed
      in healthy older persons, but often associated with increased stiffness of
      central elastic arteries, as hallmarks of aging effects on the vasculature,
      referred to as early vascular aging (EVA). In clinical practice, the increased
      arterial stiffness translates into increased brachial and central systolic blood
      pressure and corresponding pulse pressure in subjects above 50 years of age, as
      well as increased carotid-femoral pulse wave velocity (c-f PWV), a marker of
      arterial stiffness. A c-f PWV value >= 10 m/s is currently defined as a threshold
      for increased cardiovascular risk, based on consensus statement from 2012.
      Prevention and treatment strategies include a healthy lifestyle and the control
      of risk factors via appropriate drug therapy to achieve vascular protection
      related to EVA. New drugs are under development for vascular protection, for
      example the selective Angiotensin II (AT2) receptor agonist called compound 21.
      One target group for early intervention could be members of risk families
      including subjects with early onset cardiovascular disease. 

PMID- 24729937
TI  - Vascular hyperpermeability and aging.
AB  - Vascular hyperpermeability, the excessive leakage of fluid and proteins from
      blood vessels to the interstitial space, commonly occurs in traumatic and
      ischemic injuries. This hyperpermeability causes tissue vasogenic edema, which
      often leads to multiple organ failure resulting in patient death. Vascular
      hyperpermeability occurs most readily in small blood vessels as their more
      delicate physical constitution makes them an easy target for barrier dysfunction.
      A single layer of endothelial cells, linked to one another by cell adhesion
      molecules, covers the interior surface of each blood vessel. The cell adhesion
      molecules play a key role in maintaining barrier functions like the regulation of
      permeability. Aging is a major risk factor for microvascular dysfunction and
      hyperpermeability. Apart from age-related remodeling of the vascular wall,
      endothelial barrier integrity and function declines with the advancement of age.
      Studies that address the physiological and molecular basis of vascular
      permeability regulation in aging are currently very limited. There have been many
      cellular and molecular mechanisms proposed to explain aging-related endothelial
      dysfunction but their true relationship to barrier dysfunction and
      hyperpermeability is not clearly known. Among the several mechanisms that promote
      vascular dysfunction and hyperpermeability, the following are considered major
      contributors: oxidative stress, inflammation, and the activation of apoptotic
      signaling pathways. In this review we highlighted (a) the physiological, cellular
      and molecular changes that occur in the vascular system as a product of aging;
      (b) the potential mechanisms by which aging leads to barrier dysfunction and
      vascular hyperpermeability in the peripheral and the blood-brain barrier; (c) the
      mechanisms by which the age-related increases in oxidative stress, inflammatory
      markers and apoptotic signaling etc. cause endothelial dysfunction and their
      relationship to hyperpermeability; and (d) the relationship between aging,
      vascular permeability and traumatic injuries. 

PMID- 24729938
TI  - Sepsis in old age: review of human and animal studies.
AB  - Sepsis is a serious problem among the geriatric population as its incidence and
      mortality rates dramatically increase with advanced age. Despite a large number
      of ongoing clinical and basic research studies, there is currently no effective
      therapeutic strategy that rescues elderly patients with severe sepsis.
      Recognition of this problem is relatively low as compared to other age-associated
      diseases. The disparity between clinical and basic studies is a problem, and this
      is likely due, in part, to the fact that most laboratory animals used for sepsis
      research are not old while the majority of sepsis cases occur in the geriatric
      population. The objective of this article is to review recent epidemiological
      studies and clinical observations, and compare these with findings from basic
      laboratory studies which have used aged animals in experimental sepsis. 

PMID- 24729940
TI  - NAD(+) Metabolism in Age-Related Hearing Loss.
AB  - Age-related hearing loss (ARHL), a degenerative disorder characterized by age
      dependent progressive increase in the threshold of auditory sensitivity, affects
      40% of people over the age of 65, and it has emerged as an important social and
      public health problem. Various factors, including genetic and environmental
      components, are known to affect both the onset and severity of ARHL. In
      particular, age-dependent changes in cellular oxidative stress and inflammatory
      responses accompanied by altered cellular signaling and gene expression
      progressively affect the function of the auditory system and eventually lead to
      hearing impairment. Recent findings suggest that a disturbance of intracellular
      NAD(+) levels is clinically related to the progression of age-associated
      disorders. Therefore, maintenance of optimal intracellular NAD(+) levels may be a
      critical factor for cellular senescence, and thus, understanding its molecular
      signaling pathways would provide critical insights into the prevention and
      treatment of ARHL as well as other age-related diseases. In this review, we
      describe the role of NAD(+) metabolism in aging and age-related diseases,
      including ARHL, and discuss a potential strategy for prevention or treatment of
      ARHL with a particular interest in NAD(+)-dependent cellular pathways. 

PMID- 24729942
TI  - Meta-analysis of Aurora Kinase A (AURKA) Expression Data Reveals a Significant
      Correlation Between Increased AURKA Expression and Distant Metastases in Human ER
      positive Breast Cancers.

PMID- 24729939
TI  - Sepsis-induced Cardiac Mitochondrial Damage and Potential Therapeutic
      Interventions in the Elderly.
AB  - The incidence of sepsis and its attendant mortality risk are significantly
      increased with aging. Thus, severe sepsis in the elderly is likely to become an
      emerging concern in critical care units. Cardiac dysfunction is an important
      component of multi-organ failure after sepsis. In our laboratory, utilizing a
      pneumonia-related sepsis animal model, our research has been focused on the
      mechanisms underlying sepsis-induced cardiac failure. In this review, based on
      findings from others and ours, we discussed age-dependent decay in mitochondria
      and the role of mitochondrial reactive oxygen species (mtROS) in sepsis-induced
      cardiac inflammation and autophagy. Our recent discovery of a potential signal
      transduction pathway that triggers myocardial mitochondrial damage is also
      discussed. Because of the significance of mitochondria damage in the aging
      process and in sepsis pathogenesis, we hypothesize that specific enhancing
      mitochondrial antioxidant defense by mitochondria-targeted antioxidants (MTAs)
      may provide important therapeutic potential in treating elder sepsis patients. In
      this review, we summarized the categories of currently published MTA molecules
      and the results of preclinical evaluation of MTAs in sepsis and aging models. 

PMID- 24729943
TI  - Comparison Of Asymmetric Hydrogenations Of Unsaturated- Carboxylic Acids And 
      Esters.
AB  - As methodology development matures it can be difficult to discern the most
      effective ways of performing certain transformations from the rest. This review
      summarizes the most important contributions leading to asymmetric hydrogenations
      of simple unsaturated-acid and ester substrates, with the objective of
      highlighting at least the best types of catalysts for each. Achievements in the
      area are described and these reveal situations where further efforts should be
      worthwhile, and ones where more research is only likely to give diminishing
      returns. In general, our conclusions are that the most useful types of catalysts
      for unsaturated-acids and -esters tend to be somewhat different, simple
      substrates have been studied extensively, and the field is poised to address more
      complex reactions. These could be ones involving alternative, particularly
      cyclic, structures, chemoselectivity issues, and more complex substrate
      stereochemistries.

PMID- 24729941
TI  - Gender differences, aging and hormonal status in mucosal injury and repair.
AB  - As the "baby boomers" age, the percentage of the population over sixty-five years
      of age is increasing rapidly. Chronic disease management is an important
      component in the care of the elderly. The effects of aging on different organ
      systems are also pertinent; such as the weakening homeostatic response to injury
      in the older individuals. Mucosal surfaces have the largest combined surface area
      in the body and are the site of important host microbe interactions, especially
      in the gut which is prone to injury, both from local and systemic insult. This
      susceptibility has been known to increase with age. Therefore it is important to
      understand the interplay between aging, injury and recovery at the mucosal
      surface. Sex hormones play an important role in the maintenance of the mucosal
      barrier function as well as the mucosa associated immune function in both
      genders. Menopause in women is a defined time period in which major hormonal
      changes occur such as a decline in systemic estradiol levels. The differential
      levels of sex hormones contribute to the sexual dimorphism seen in response to
      injury at the mucosal surface, prior to and following menopause. Thus the effect
      of sex hormone and aging on mucosal mechanisms in response to injury is an
      important area of investigation. 

PMID- 24729944
TI  - Human Allogeneic Bone Marrow and Adipose Tissue Derived Mesenchymal Stromal Cells
      Induce CD8+ Cytotoxic T Cell Reactivity.
AB  - INTRODUCTION: For clinical applications, Mesenchymal Stromal Cells (MSC) can be
      isolated from bone marrow and adipose tissue of autologous or allogeneic origin.
      Allogeneic cell usage has advantages but may harbor the risk of sensitization
      against foreign HLA. Therefore, we evaluated whether bone marrow and adipose
      tissue-derived MSC are capable of inducing HLA-specific alloreactivity. METHODS:
      MSC were isolated from healthy human Bone Marrow (BM-MSC) and adipose tissue
      (ASC) donors. Peripheral Blood Mononuclear Cells (PBMC) were co-cultured with HLA
      AB mismatched BM-MSC or ASC precultured with or without IFNy. After isolation via
      FACS sorting, the educated CD8+ T effector populations were exposed for 4 hours
      to Europium labeled MSC of the same HLA make up as in the co-cultures or with
      different HLA. Lysis of MSC was determined by spectrophotometric measurement of
      Europium release. RESULTS: CD8+ T cells educated with BM-MSC were capable of HLA
      specific lysis of BM-MSC. The maximum lysis was 24% in an effector:target (E:T)
      ratio of 40:1. Exposure to IFNgamma increased HLA-I expression on BM-MSC and
      increased lysis to 48%. Co-culturing of PBMC with IFNgamma-stimulated BM-MSC
      further increased lysis to 76%. Surprisingly, lysis induced by ASC was
      significantly lower. CD8+ T cells educated with ASC induced a maximum lysis of
      13% and CD8+ T cells educated with IFNgamma-stimulated ASC of only 31%.
      CONCLUSION: Allogeneic BM-MSC, and to a lesser extend ASC, are capable of
      inducing HLA specific reactivity. These results should be taken into
      consideration when using allogeneic MSC for clinical therapy.

PMID- 24729945
TI  - Cardiac Vagal Tone and Quality of Parenting Show Concurrent and Time-Ordered
      Associations That Diverge in Abusive, Neglectful, and Non-Maltreating Mothers.
AB  - Concurrent and lagged maternal respiratory sinus arrhythmia (RSA) was monitored
      in the context of parenting. One hundred and forty-one preschooler-mother dyads
      involved with child welfare as documented perpetrators of child abuse or neglect,
      or non-maltreating (non-CM)-were observed completing a resting baseline and joint
      challenge task. Parenting behaviors were coded using SASB (Benjamin, 1996) and
      maternal RSA was simultaneously monitored, longitudinally-nested within-person
      (WP), and subjected to MLM. Abusive and neglectful mothers displayed less
      positive parenting and more strict/hostile control, relative to non-CM mothers.
      Non-CM mothers displayed greater WP heterogeneity in variance over time in their
      RSA scores, and greater consistency over time in their parenting behaviors,
      relative to abusive or neglectful mothers. CM group also moderated concurrent and
      lagged WP associations in RSA and positive parenting. When abusive mothers
      displayed lower RSA in a given epoch, relative to their task average, they showed
      concurrent increases in positive parenting, and higher subsequent levels of
      hostile control in the following epoch, suggesting that it is physiologically
      taxing for abusive mothers to parent in positive ways. In contrast, lagged
      effects for non-CM mothers were observed in which RSA decreases led to subsequent
      WP increases in positive parenting and decreases in control. Reversed models were
      significant only for neglectful mothers: Increases in positive parenting led to
      subsequent increases in RSA levels, and increases in strict, hostile control led
      to subsequent RSA decreases. These results provide new evidence that concurrent
      and time-ordered coupling in maternal physiology and behavior during parenting
      vary in theoretically meaningful ways across CM and non-CM mothers. Implications
      for intervention and study limitations are discussed.

PMID- 24729946
TI  - Perceived Unfair Treatment and Problem Drinking among U.S. Navy Careerists.
AB  - This mixed method paper assessed interrelationships of unfair treatment at work,
      stress, and problem drinking amongst a sample of U.S. Navy careerists. Survey
      data from current drinkers (n=2380) were analyzed, along with qualitative
      interviews from a quota sample of 81. More women than men (51.4% vs. 16.2%)
      reported gender unfair treatment; approximately 20% of respondents reported
      ethnic/racial unfair treatment. Unfair treatment was associated with likelihood
      of problem drinking, but associations were attenuated after adjusting for
      frequency of work problems and expecting alcohol to alleviate stress. Qualitative
      results revealed contexts of unfair treatment within bureaucratic structures,
      tradition, norms, and role modeling.

PMID- 24729947
TI  - Efficacy of Gastrografin(r) Compared with Standard Conservative Treatment in
      Management of Adhesive Small Bowel Obstruction at Mulago National Referral
      Hospital.
AB  - INTRODUCTION: The treatment of adhesive small bowel obstruction is controversial,
      with both operative and non-operative management practiced in different centers
      worldwide. Non-operative management is increasingly getting popular, though
      operative rates still remain high. A study to compare the efficacy of an oral
      water-soluble medium (Gastrografin(r)) with standard conservative management,
      both non-operative methods, in the management of this condition was conducted in
      a tertiary Sub Saharan hospital. METHODS: An open randomised controlled clinical
      trial was conducted between September 2012 and March 2013 at Mulago National
      Referral and Teaching Hospital, Uganda. Fifty patients of both genders, with
      adhesive small bowel obstruction, in the hospital's emergency and general
      surgical wards were included. Randomisation was to Gastrografin(r) and standard
      conservative treatment groups. The primary outcomes were: the time interval
      between admission and relief of obstruction, the length of hospital stay, and the
      rates of operative surgery. RESULTS: All 50 recruited patients were followed up
      and analysed; 25 for each group. In the Gastrografin(r) group, 22 (88%) patients
      had relief of obstruction following the intervention, with 3 (12%) requiring
      surgery. The conservative treatment group had 16 (64%) patients relieved of
      obstruction conservatively, and 9 (36%) required surgery. The difference in
      operative rates between the two groups was not statistically significance (P =
      0.67). Average time to relief of obstruction was shorter in the Gastrografin(r)
      group (72.52 hrs) compared to the conservative treatment group (117.75 hrs), a
      significant difference (P = 0.023). The average length of hospital stay was
      shorter in the Gastrografin(r) group (5.62 days) compared to the conservative
      treatment group (10.88 days), a significant difference (P = 0.04). CONCLUSION:
      The use of Gastrografin(r) in patients with adhesive small bowel obstruction
      helps in earlier resolution of obstruction and reduces the length of hospital
      stay compared with standard conservative management. Its role in reducing the
      rate of laparotomies remains inconclusive.

PMID- 24729949
TI  - Genetic discoveries in AD using CSF amyloid and tau.
AB  - The use of cerebrospinal fluid levels of Abeta42 and pTau181 as endophenotypes
      for genetic studies of Alzheimer's disease (AD) has led to successful
      identification of both rare and common AD risk variants. In addition, this
      approach has provided meaningful hypotheses for the biological mechanisms by
      which known AD risk variants modulate the disease process. In this article we
      discuss these successes and outline challenges to effective and continued
      applications of this approach. We contrast the statistical power of this approach
      with traditional case-control designs and discuss solutions to address challenges
      in quality control and data analysis for these phenotypes. Finally, we discuss
      the potential for the use of this approach with larger samples as well as the
      incorporation of next generation sequencing and for future work with other
      endophenotypes for AD.

PMID- 24729948
TI  - Beclin 1, an Essential Component and Master Regulator of PI3K-III in Health and
      Disease.
AB  - Autophagy is a cell 'self-digestion' pathway involving the synthesis, trafficking
      and delivery of autophagosomes to lysosomes for degradation. Beclin 1 is a core
      component of the class III phosphatidylinositol 3-kinase (PI3K-III) complex,
      which plays an important role in membrane trafficking and restructuring involved
      in autophagy, endocytosis, cytokinesis and phagocytosis. To date Beclin 1 has
      largely been characterized in the context of autophagy; it modulates the lipid
      kinase activity of PI3K-III catalytic unit VPS34, which generates
      phosphatidylinositol 3-phosphate (PI(3)P), enabling the recruitment of a number
      of autophagy proteins involved in the nucleation of the autophagosome. Beclin 1
      seems to function as an adaptor for recruiting multiple proteins that modulate
      VPS34. The recent identification of Beclin 1 protein modifications has shed light
      on its regulation in autophagy, and the discovery of non-autophagy functions of
      Beclin 1 has expanded our view of Beclin 1's involvement in tissue homeostasis
      and human diseases.

PMID- 24729950
TI  - Exploring barriers and facilitators in eating disorders treatment among Latinas
      in the United States.
AB  - : The purpose of this study was to explore facilitators and barriers that may
      contribute to, or prevent, the engagement and retention of Latinos in eating
      disorders (EDs) treatment. OBJECTIVE: The main objective of this investigation
      was to explore more fully the facilitators and barriers that may contribute to or
      prevent the engagement and retention of Latinos/as in EDs treatment. METHODS: A
      qualitative design based on grounded theory was used to guide in-depth interviews
      with 5 Latinas (mean age 31.2 years) with history of EDs and with 5 Latino mental
      health providers (mean age 36.4 years). RESULTS: Six main themes were found in
      the discussion with patients and mental health providers: immigration stress,
      treatment experience in the U.S., facilitators of help seeking, barriers to help
      seeking, treatment needs, and facilitators of treatment retention. For patients,
      lack of information about EDs and lack of bilingual treatment were identified as
      practical barriers. Other emotional factors such as stigma, fear of not being
      understood, family privacy and not being ready to change were identified as
      barriers to seeking help. Among facilitator factors that encouraged patients to
      seek help, the most salient were the perception of the severity of the ED and
      emotional distress. For treatment retention, family support was a key element
      among patients. For providers, offering short-term treatment and directive
      treatment were seen as relevant factors for treatment retention in Latinos.
      CONCLUSIONS: A culturally sensitive intervention model for Latinas with EDs in
      the U.S. is discussed addressing four levels: patient; family; providers; and
      system.

PMID- 24729951
TI  - Problem-Solving Therapy in the Elderly.
AB  - We systematically reviewed randomized clinical trials of problem-solving therapy
      (PST) in older adults. Our results indicate that PST led to greater reduction in
      depressive symptoms of late-life major depression than supportive therapy (ST)
      and reminiscence therapy. PST resulted in reductions in depression comparable
      with those of paroxetine and placebo in patients with minor depression and
      dysthymia, although paroxetine led to greater reductions than placebo. In home
      health care, PST was more effective than usual care in reducing symptoms of
      depression in undiagnosed patients. PST reduced disability more than ST in
      patients with major depression and executive dysfunction. Preliminary data
      suggest that a home-delivered adaptation of PST that includes environmental
      adaptations and caregiver involvement is efficacious in reducing disability in
      depressed patients with advanced cognitive impairment or early dementia. In
      patients with macular degeneration, PST led to improvement in vision-related
      disability comparable to that of ST, but PST led to greater improvement in
      measures of vision-related quality of life. Among stroke patients, PST
      participants were less likely to develop a major or minor depressive episode than
      those receiving placebo treatment, although the results were not sustained in a
      more conservative statistical analysis. Among patients with macular degeneration,
      PST participants had significantly lower 2-month incidence rates of major
      depression than usual care participants and were less likely to suffer persistent
      depression at 6 months. Finally, among stroke patients, PST participants were
      less likely to develop apathy than those receiving placebo treatment. PST also
      has been delivered via phone, Internet, and videophone, and there is evidence of
      feasibility and acceptability. Further, preliminary data indicate that PST
      delivered through the Internet resulted in a reduction in depression comparable
      with that of in-person PST in home-care patients. PST delivered via videophone
      results in an improvement in hospice caregivers' quality of life and a reduction
      in anxiety comparable to those of in-person PST. PST-treated patients with
      cognitive impairment may require additional compensatory strategies, such as
      written notes, memory devices, environmental adaptations, and caregiver
      involvement.

PMID- 24729952
TI  - Abnormal Bursting as a Pathophysiological Mechanism in Parkinson's Disease.
AB  - Despite remarkable advances in Parkinson's disease (PD) research, the
      pathophysiological mechanisms causing motor dysfunction remain unclear, possibly
      delaying the advent of new and improved therapies. Several such mechanisms have
      been proposed including changes in neuronal firing rates, the emergence of
      pathological oscillatory activity, increased neural synchronization, and abnormal
      bursting. This review focuses specifically on the role of abnormal bursting of
      basal ganglia neurons in PD, where a burst is a physiologically-relevant,
      transient increase in neuronal firing over some reference period or activity.
      After reviewing current methods for how bursts are detected and what the
      functional role of bursts may be under normal conditions, existing studies are
      reviewed that suggest that bursting is abnormally increased in PD and that this
      increases with worsening disease. Finally, the influence of therapeutic
      approaches for PD such as dopamine-replacement therapy with levodopa or dopamine
      agonists, lesions, or deep brain stimulation on bursting is discussed. Although
      there is insufficient evidence to conclude that increased bursting causes motor
      dysfunction in PD, current evidence suggests that targeted investigations into
      the role of bursting in PD may be warranted.

PMID- 24729953
TI  - Integrating in vitro organ-specific function with the microcirculation.
AB  - There is significant interest within the tissue engineering and pharmaceutical
      industries to create 3D microphysiological systems of human organ function. The
      interest stems from a growing concern that animal models and simple 2D culture
      systems cannot replicate essential features of human physiology that are critical
      to predict drug response, or simply to develop new therapeutic strategies to
      repair or replace damaged organs. Central to human organ function is a
      microcirculation that not only enhances the rate of nutrient and waste transport
      by convection, but also provides essential additional physiological functions
      that can be specific to each organ. This review highlights progress in the
      creation of in vitro functional microvessel networks, and emphasizes organ
      specific functional and structural characteristics that should be considered in
      the future mimicry of four organ systems that are of primary interest: lung,
      brain, liver, and muscle (skeletal and cardiac).

PMID- 24729954
TI  - Vascular Mimicry: Concepts and Implications for Anti-Angiogenic Therapy.
AB  - As in normal tissues, solid tumors depend on vascular networks to supply blood,
      oxygen, and nutrients. Tumor blood vessels are formed by common processes of
      neovascularization for example endothelial sprouting. However, some tumors have
      alternative and unexpected mechanisms of neovascularization at their disposal. In
      a process termed "vascular mimicry," tumors create their own, tumor cell-lined
      channels for fluid transport independent of typical modes of angiogenesis. These
      tumor cell-lined conduits may express endothelial-selective markers and anti
      coagulant factors which allow for anastamosis with host endothelium. In this
      review, we explore the current status of vascular mimicry research, highlighting
      recent evidence which strengthens the hypothesis for this unusual ability of
      tumor cells. Furthermore, we address the theoretical possibility that vascular
      mimicry provides a mechanism whereby tumors could escape anti-angiogenic
      therapies.

PMID- 24729955
TI  - Jailing Technique Using a Catheter-based Open-cell Stent System in Internal
      Carotid Artery Sidewall Aneurysms Unfeasible to Simple Coiling.
AB  - OBJECTIVE: An open cell stent system may offer better apposition of cell struts
      to vessel wall than a closed cell stent system in acute vasculature. The purpose
      of this study was to evaluate the feasibility of coiling using the jailing
      technique with the Neuroform EZ stent system. METHODS: The jailing technique
      using the open-cell stent system of the Neuroform EZ stent was planned in 22
      consecutive patients with 22 cerebral aneurysms. We retrospectively evaluated the
      technical success of the jailing technique and the occurrence of interference
      between two microcatheters as well as the factors influencing this interference.
      RESULTS: The jailing technique was successful in 19/22 patients (86.4%), and
      interference between two microcatheters occurred in 6/21 (28.6%). The jailing
      technique failed in 3/22 patients, with problems that included failure of the
      stent delivery system to advance into the positioned microcatheter in one,
      interference between the microcatheters during the advancement of the stent
      delivery system in one, and failure of microcatheter insertion into the aneurysm
      sac in the remaining patient. Interference between the two microcatheters
      developed during the advance of the stent delivery system into the positioned
      microcatheter in all cases. One factor that influences interference between two
      microcatheters more than expected by chance is the carotid siphon angle (p =
      0.019). CONCLUSION: The acuteness of the carotid siphon angle influences the
      interference between two microcatheters. Therefore, the jailing technique using
      the Neuroform EZ stent should be performed carefully in cerebral aneurysms with
      an acute carotid siphon angle because the procedure may possibly fail.

PMID- 24729956
TI  - A Self-expanding Nitinol Stent (Enterprise) for the Treatment of Wide-necked
      Intracranial Aneurysms: Angiographic and Clinical Results in 40 Aneurysms.
AB  - OBJECTIVE: Self-expanding stents are increasingly used for the treatment of
      complex intracranial aneurysms. The purpose of this study was to evaluate the
      usefulness and safety of a self-expanding nitinol stent (Enterprise) in the
      treatment of wide-necked intracranial aneurysms. METHODS: This was a
      retrospective study of 39 patients with 40 wide-necked intracranial aneurysms who
      were enrolled in a single-center registry of patients treated with the Enterprise
      between June 2009 and December 2011. Thirty patients were asymptomatic, four had
      cerebrovascular accident sequelae, and five had suffered subarachnoid hemorrhage.
      One aneurysm had reopened after prior coil embolization, while 39 had not been
      treated. Clinical charts, procedural data, and angiographic results, including
      both immediate post-procedural angiograms and follow-up imaging, were reviewed.
      RESULTS: The mean neck size of the aneurysms was 5.58 mm (range 3-15.1 mm).
      Embolization was successful in all patients. There were five procedure-related
      events. There were no fatalities, but one procedure-related morbidity was noted.
      The immediate angiographic results included eight complete occlusions (20%), six
      remnant necks (15%), and 26 remnant sacs (65%). At angiographic follow-up (mean:
      11.3 months), out of 18 of the aneurysms treated with stent-assisted coiling,
      there were 13 (72.2%) complete occlusions, four (22.2%) remnant necks, and one
      recanalization (5.6%). CONCLUSION: Stent-assisted coiling using the Enterprise is
      effective for the treatment of wide-necked intracranial aneurysms. Further
      angiographic and clinical follow-up investigation will be needed for evaluation
      of the long-term outcomes.

PMID- 24729957
TI  - Predictive Capability of the Spetzler-Martin versus Supplementary Grading Scale
      for Microsurgical Outcomes of Cerebellar Arteriovenous Malformations.
AB  - The recently described supplementary grading scale may be superior to the widely
      used Spetzler-Martin grading scale in the prediction of microsurgical outcomes
      for cerebellar arteriovenous malformations (AVM). We report two cases of ruptured
      cerebellar AVMs with the same Spetzler-Martin grade but different supplementary
      grades treated with microsurgical resection. Both patients had symptomatic
      brainstem compression from cerebellar hematomas and subsequently underwent
      uncomplicated surgeries; however, their outcomes were significantly different. It
      has previously been proposed that AVMs distort cerebellar anatomy in a different
      manner than supratentorial cerebral anatomy thereby potentially resulting in
      misrepresentation when utilizing the Spetzler-Martin grading scale. However, the
      components of the supplementary grading scale are independent of cerebellar
      anatomy, which may explain why it has been shown to be better than the Spetzler
      Martin grading scale for prediction of surgical outcomes. In addition, due to the
      smaller volume of the posterior fossa compared to the supratentorial compartment,
      rupture of cerebellar AVMs may result in rapid and catastrophic neurological
      compromise. Therefore, the role of microsurgery may be more critical for AVMs of
      the cerebellar than for those located elsewhere. Simple and effective grading
      systems are invaluable tools for clinical and surgical decision-making, although
      the decisions rendered should always be made in conjunction with the patient's
      presentation and the physician's experience. 

PMID- 24729958
TI  - Communicating hydrocephalus accompanied by arachnoid cyst in aneurismal
      subarachnoid hemorrhage.
AB  - The authors describe a case of communicating hydrocephalus accompanied by an
      arachnoid cyst in an aneurismal subarachnoid hemorrhage. A 69-year-old female was
      referred to our clinic due to the sudden onset of a headache. A head computed
      tomography scan demonstrated an arachnoid cyst in the right middle fossa with a
      mass effect and diffuse subarachnoid hemorrhage. Digital subtraction angiography
      then revealed a left internal carotid-posterior communicating artery aneurysm.
      The neck of the aneurysm was clipped successfully and the post-operative period
      was uneventful. However, two months after discharge, the patient reported that
      her mental status had declined over previous weeks. A cranial computed tomography
      scan revealed an interval increase in the size of the ventricle and arachnoid
      cyst causing a midline shift. Simultaneous navigation guided ventriculoperitoneal
      shunt and cystoperitoneal shunt placement resulted in remarkable radiological and
      clinical improvements. 

PMID- 24729959
TI  - Simultaneous multiple Basal Ganglia and cerebellar hemorrhage: case report.
AB  - A 35-year-old man presented with simultaneous multiple intracranial hematomas in
      the right cerebellar dentate nucleus and left basal ganglia. The hematomas were
      visible by computed tomography performed within two hours of the patient's
      arrival. The initial computed tomography showed acute hemorrhage in the left
      basal ganglia and dentate nucleus in cerebellum. The patient then experienced a
      change of consciousness due to newly developed hydrocephalus, and emergent extra
      ventricular drainage was performed. By discharge, fortunately, the patient was
      fully recovered. 

PMID- 24729960
TI  - Intra-arterial Onyx Embolization of Vertebral Body Lesions.
AB  - While Onyx embolization of cerebrospinal arteriovenous shunts is well
      established, clinical researchers continue to broaden applications to other
      vascular lesions of the neuraxis. This report illustrates the application of Onyx
      (eV3, Plymouth, MN) embolization to vertebral body lesions, specifically, a
      vertebral hemangioma and renal cell carcinoma vertebral body metastatic lesion. 

PMID- 24729961
TI  - Ophthalmic artery occlusion after carotid revascularization.
AB  - Distal embolization resulting from carotid angioplasty and stenting (CAS) occurs
      mainly in the cerebral hemisphere. We report a case of ophthalmic artery
      occlusion after carotid revascularization. A 75-year old man received emergency
      CAS for cervical internal carotid artery occlusion. Two months later, the patient
      was readmitted for decreased visual acuity. We found ophthalmic artery occlusion
      that was not noticed soon after CAS. Although ophthalmic artery occlusion after
      CAS is rare, endovascular neurosurgeons should be aware of this potential
      complication. 

PMID- 24729962
TI  - Application of Hybrid Functional Groups to Predict ATP Binding Proteins.
AB  - The ATP binding proteins exist as a hybrid of proteins with Walker A motif and
      universal stress proteins (USPs) having an alternative motif for binding ATP.
      There is an urgent need to find a reliable and comprehensive hybrid predictor for
      ATP binding proteins using whole sequence information. In this paper the open
      source LIBSVM toolbox was used to build a classifier at 10-fold cross-validation.
      The best hybrid model was the combination of amino acid and dipeptide composition
      with an accuracy of 84.57% and Mathews correlation coefficient (MCC) value of
      0.693. This classifier proves to be better than many classical ATP binding
      protein predictors. The general trend observed is that combinations of
      descriptors performed better and improved the overall performances of individual
      descriptors, particularly when combined with amino acid composition. The work
      developed a comprehensive model for predicting ATP binding proteins irrespective
      of their functional motifs. This model provides a high probability of success for
      molecular biologists in predicting and selecting diverse groups of ATP binding
      proteins irrespective of their functional motifs.

PMID- 24729963
TI  - Superoxide dismutase: a predicting factor for boar semen characteristics for
      short-term preservation.
AB  - Superoxide dismutase (SOD), total antioxidant capacity (TAC), and thiobarbituric
      acid reactive substances (TBARS) in seminal plasma were evaluated on the basis of
      receiver operating characteristics (ROC) analysis as predictors for
      distinguishing satisfactory from unsatisfactory boar semen samples after storage.
      SOD on day 0 correlated significantly with progressive motility (r=-0.686;
      P<0.05) and viability (r=-0.513; P<0.05) after storage; TBARS correlated only
      with motility (r=-0.480; P<0.05). Semen samples that, after 3 days of storage,
      fulfilled all criteria for semen characteristics (viability>85%, motility>70%,
      progressive motility>25%, and normal morphology>50%) had significantly lower SOD
      levels on the day 0 than those with at least one criterion not fulfilled (P<0.05)
      following storage. SOD levels of less than 1.05 U/mL predicted with 87.5%
      accuracy that fresh semen will suit the requirements for satisfactory semen
      characteristics after storage, while semen with SOD levels higher than 1.05 U/mL
      will not fulfill with 100% accuracy at least one semen characteristic after
      storage. These results support the proposal that SOD in fresh boar semen can be
      used as a predictor of semen quality after storage.

PMID- 24729964
TI  - Evaluating word representation features in biomedical named entity recognition
      tasks.
AB  - Biomedical Named Entity Recognition (BNER), which extracts important entities
      such as genes and proteins, is a crucial step of natural language processing in
      the biomedical domain. Various machine learning-based approaches have been
      applied to BNER tasks and showed good performance. In this paper, we
      systematically investigated three different types of word representation (WR)
      features for BNER, including clustering-based representation, distributional
      representation, and word embeddings. We selected one algorithm from each of the
      three types of WR features and applied them to the JNLPBA and BioCreAtIvE II BNER
      tasks. Our results showed that all the three WR algorithms were beneficial to
      machine learning-based BNER systems. Moreover, combining these different types of
      WR features further improved BNER performance, indicating that they are
      complementary to each other. By combining all the three types of WR features, the
      improvements in F-measure on the BioCreAtIvE II GM and JNLPBA corpora were 3.75%
      and 1.39%, respectively, when compared with the systems using baseline features.
      To the best of our knowledge, this is the first study to systematically evaluate
      the effect of three different types of WR features for BNER tasks. 

PMID- 24729965
TI  - Effect of age-related cartilage turnover on serum C-telopeptide of collagen type
      II and osteocalcin levels in growing rabbits with and without surgically induced
      osteoarthritis.
AB  - This study aims to determine the effect of age-related cartilage turnover on the
      serum C-telopeptide of type II collagen (CTX-II) and osteocalcin (OC) levels in
      growing rabbits with and without surgically induced osteoarthritis. Twenty-four
      New Zealand male 3-month-old rabbits were randomized into three operated groups
      (n=6 per group, with surgically induced osteroarthritis in the right knee; after
      blood sampling, the knees were harvested following euthanization at 2, 3, and 6
      months after surgery) and a control group (n=6, blood samples were obtained
      monthly between 3 and 15 months). Histomorphologically, the medial femoral
      condyles, particularly the central parts, harbored the most severe osteoarthritic
      changes among the operated rabbits. The serum levels of CTX-II and OC decreased
      in the controls from 3 to 11 months and then remained stable. No significant
      differences in the serum CTX-II and OC levels between the osteoarthritic rabbits
      and controls were observed. The osteoarthritic-to-normal ratios (ONRs, the ratios
      of serum CTX-II or OC levels in osteoarthritic rabbits to those of the controls
      at same ages) enabled an overall assessment of osteoarthritis and age-related
      cartilage turnover. Elevated CTX-II ONRs were observed in rabbits with mild to
      advanced osteoarthritis. However, the OC ONRs were unhelpful in assessing
      osteoarthritic growing rabbits.

PMID- 24729967
TI  - The effect of mycotoxin deoxynivalenol on haematological and biochemical
      indicators and histopathological changes in rainbow trout (Oncorhynchus mykiss).
AB  - Deoxynivalenol (DON), produced by the Fusarium genus, is a major contaminant of
      cereal grains used in the production of fish feed. The effect of mycotoxin
      deoxynivalenol on rainbow trout (Oncorhynchus mykiss) was studied using a
      commercial feed with the addition of DON in a dose of 2 mg/kg feed. The fish
      (n=40) were exposed to the mycotoxin for 23 days. The trout were divided into two
      groups, control and experimental groups. Control groups were fed a commercial
      feed naturally contaminated with a low concentration of DON (225  MUg/kg feed);
      experimental groups were fed a commercial feed with the addition of DON (1964 
      MUg/kg feed). Plasma biochemical and haematological indices, biometric
      parameters, and histopathological changes were assessed at the end of the
      experiment. The experimental groups showed significantly lower values in MCH
      (P<0.05). In biochemical indices, after 23-day exposure, a significant decrease
      in glucose, cholesterol (P<0.05), and ammonia (P<0.01) was recorded in the
      experimental group compared to the control group. Our assessment showed no
      significant changes in biometric parameters. The histopathological examination
      revealed disorders in the caudal kidney of the exposed fish. The obtained data
      show the sensitivity of rainbow trout (O. mykiss) to deoxynivalenol.

PMID- 24729966
TI  - The role of vitamin D deficiency and vitamin d receptor genotypes on the degree
      of collateralization in patients with suspected coronary artery disease.
AB  - We determined the association of vitamin D deficiency and the FokI polymorphism
      of the vitamin D receptor (VDR) gene in 760 patients who underwent angiography
      due to suspected coronary artery disease (CAD). Angiography and the Rentrop
      scoring system were used to classify the severity of CAD in each patient and to
      grade the extent of collateral development, respectively. Polymerase chain
      reaction-restriction fragment length polymorphism (PCR-RFLP) was used to
      determine the FokI VDR gene polymorphism. The prevalence of severe vitamin D
      deficiency (serum 25(OH)D<10 ng/mL) was significantly higher in patients with at
      least one stenotic coronary artery compared to those without any stenotic
      coronary arteries. Severe vitamin D deficiency was not independently associated
      with collateralization, but it was significantly associated with the VDR
      genotypes. In turn, VDR genotype was independently associated with the degree of
      collateralization; the Rentrop scores were the highest in FF, intermediate in Ff,
      and the lowest in the ff genotype. The results show that FokI polymorphism is
      independently associated with collateralization. Additionally, vitamin D
      deficiency is more prevalent in patients with CAD that may result from FokI
      polymorphism. Therefore, maintaining a normal vitamin D status should be a high
      priority for patients with CAD.

PMID- 24729968
TI  - TF2LncRNA: identifying common transcription factors for a list of lncRNA genes
      from ChIP-Seq data.
AB  - High-throughput genomic technologies like lncRNA microarray and RNA-Seq often
      generate a set of lncRNAs of interest, yet little is known about the
      transcriptional regulation of the set of lncRNA genes. Here, based on ChIP-Seq
      peak lists of transcription factors (TFs) from ENCODE and annotated human lncRNAs
      from GENCODE, we developed a web-based interface titled "TF2lncRNA," where TF
      peaks from each ChIP-Seq experiment are crossed with the genomic coordinates of a
      set of input lncRNAs, to identify which TFs present a statistically significant
      number of binding sites (peaks) within the regulatory region of the input lncRNA
      genes. The input can be a set of coexpressed lncRNA genes or any other cluster of
      lncRNA genes. Users can thus infer which TFs are likely to be common
      transcription regulators of the set of lncRNAs. In addition, users can retrieve
      all lncRNAs potentially regulated by a specific TF in a specific cell line of
      interest or retrieve all TFs that have one or more binding sites in the
      regulatory region of a given lncRNA in the specific cell line. TF2LncRNA is an
      efficient and easy-to-use web-based tool. 

PMID- 24729969
TI  - A survey on evolutionary algorithm based hybrid intelligence in bioinformatics.
AB  - With the rapid advance in genomics, proteomics, metabolomics, and other types of
      omics technologies during the past decades, a tremendous amount of data related
      to molecular biology has been produced. It is becoming a big challenge for the
      bioinformatists to analyze and interpret these data with conventional intelligent
      techniques, for example, support vector machines. Recently, the hybrid
      intelligent methods, which integrate several standard intelligent approaches, are
      becoming more and more popular due to their robustness and efficiency.
      Specifically, the hybrid intelligent approaches based on evolutionary algorithms
      (EAs) are widely used in various fields due to the efficiency and robustness of
      EAs. In this review, we give an introduction about the applications of hybrid
      intelligent methods, in particular those based on evolutionary algorithm, in
      bioinformatics. In particular, we focus on their applications to three common
      problems that arise in bioinformatics, that is, feature selection, parameter
      estimation, and reconstruction of biological networks. 

PMID- 24729970
TI  - A new sampling method for spleen stiffness measurement based on quantitative
      acoustic radiation force impulse elastography for noninvasive assessment of
      esophageal varices in newly diagnosed HCV-related cirrhosis.
AB  - In our study, we evaluated the feasibility of a new sampling method for splenic
      stiffness (SS) measurement by Quantitative Acoustic Radiation Force Impulse
      Elastography (Virtual Touch Tissue Quantification (VTTQ)).We measured SS in 54
      patients with HCV-related cirrhosis of whom 28 with esophageal varices (EV), 27
      with Chronic Hepatitis C (CHC) F1-F3, and 63 healthy controls. VTTQ-SS was
      significantly higher among cirrhotic patients with EV (3.37 m/s) in comparison
      with controls (2.19 m/s, P<0.001), CHC patients (2.37 m/s, P<0.001), and
      cirrhotic patients without EV (2.7 m/s, P<0.001). Moreover, VTTQ-SS was
      significantly higher among cirrhotic patients without EV in comparison with both
      controls (P<0.001) and CHC patients (P<0.01). The optimal VTTQ-SS cut-off value
      for predicting EV was 3.1 m/s (AUROC=0.96, sensitivity 96.4%, specificity 88.5%,
      positive predictive value 90%, negative predictive value 96%, positive likelihood
      ratio 8.36, and negative likelihood ratio 0.04). In conclusion, VTTQ-SS is a
      promising noninvasive and reliable diagnostic tool to screen cirrhotic patients
      for EV and reduce the need for upper gastrointestinal endoscopy. By using our cut
      off value of 3.1 m/s, we would avoid endoscopy in around 45% of cirrhotic
      subjects, with significant time and cost savings.

PMID- 24729971
TI  - Identifying gastric cancer related genes using the shortest path algorithm and
      protein-protein interaction network.
AB  - Gastric cancer, as one of the leading causes of cancer related deaths worldwide,
      causes about 800,000 deaths per year. Up to now, the mechanism underlying this
      disease is still not totally uncovered. Identification of related genes of this
      disease is an important step which can help to understand the mechanism
      underlying this disease, thereby designing effective treatments. In this study,
      some novel gastric cancer related genes were discovered based on the knowledge of
      known gastric cancer related ones. These genes were searched by applying the
      shortest path algorithm in protein-protein interaction network. The analysis
      results suggest that some of them are indeed involved in the biological process
      of gastric cancer, which indicates that they are the actual gastric cancer
      related genes with high probability. It is hopeful that the findings in this
      study may help promote the study of this disease and the methods can provide new
      insights to study various diseases. 

PMID- 24729972
TI  - Genotype-related effect of crowding stress on blood pressure and vascular
      function in young female rats.
AB  - This study investigated the influence of chronic crowding stress on nitric oxide
      (NO) production, vascular function and oxidative status in young Wistar-Kyoto
      (WKY), borderline hypertensive (BHR) and spontaneously hypertensive (SHR) female
      rats. Five-week old rats were exposed to crowding for two weeks. Crowding
      elevated plasma corticosterone (P<0.05) and accelerated BP (P<0.01 versus basal)
      only in BHR. NO production and superoxide concentration were significantly higher
      in the aortas of control BHR and SHR versus WKY. Total acetylcholine (ACh)
      induced relaxation in the femoral artery was reduced in control SHR versus WKY
      and BHR, and stress did not affect it significantly in any genotype. The
      attenuation of ACh-induced relaxation in SHR versus WKY was associated with
      reduction of its NO-independent component. Crowding elevated NO production in all
      strains investigated but superoxide concentration was increased only in WKY,
      which resulted in reduced NO-dependent relaxation in WKY. In crowded BHR and SHR,
      superoxide concentration was either unchanged or reduced, respectively, but NO
      dependent relaxation was unchanged in both BHR and SHR versus their respective
      control group. This study points to genotype-related differences in stress
      vulnerability in young female rats. The most pronounced negative influence of
      stress was observed in BHR despite preserved endothelial function.

PMID- 24729973
TI  - A multiplex snapback primer system for the enrichment and detection of JAK2 V617F
      and MPL W515L/K mutations in Philadelphia-negative myeloproliferative neoplasms.
AB  - A multiplex snapback primer system was developed for the simultaneous detection
      of JAK2 V617F and MPL W515L/K mutations in Philadelphia chromosome- (Ph-)
      negative myeloproliferative neoplasms (MPNs). The multiplex system comprises two
      snapback versus limiting primer sets for JAK2 and MPL mutation enrichment and
      detection, respectively. Linear-After exponential (LATE) PCR strategy was
      employed for the primer design to maximize the amplification efficiency of the
      system. Low ionic strength buffer and rapid PCR protocol allowed for selective
      amplification of the mutant alleles. Amplification products were analyzed by
      melting curve analysis for mutation identification. The multiplex system archived
      0.1% mutation load sensitivity and <5% coefficient of variation inter-/intra
      assay reproducibility. 120 clinical samples were tested by the multiplex snapback
      primer assay, and verified with amplification refractory system (ARMS),
      quantitative PCR (qPCR) and Sanger sequencing method. The multiplex system, with
      a favored versatility, provided the molecular diagnosis of Ph-negative MPNs with
      a suitable implement and simplified the genetic test process. 

PMID- 24729975
TI  - Zenker's diverticulum: carbon dioxide laser endoscopic surgery.
AB  - Nowadays endoscopic diverticulotomy is the surgical approach of the first choice
      in treatment of Zenker's diverticulum. We report our experience with this
      procedure and try to sum up recent recommendations for management of surgery and
      postoperative care. Data of 34 patients with Zenker's diverticulum, treated by
      endoscopic carbon dioxide laser diverticulotomy at the Department of
      Otorhinolaryngology and Head and Neck Surgery, 1st Faculty of Medicine, Charles
      University, University Hospital Motol, Prague, Czech Republic, were prospectively
      stored and followed in relatively short period from May 2009 to December 2013.
      The average length of diverticulum was 32 mm. The average duration of surgery was
      32 min. The patients were fed via feeding tube for 6.1 days and antibiotics were
      administered for 7 days. Mean hospitalization time was 7.4 days. We observed one
      transient recurrent laryngeal nerve paralysis and no other serious complications.
      Recurrence rate was 3%. We recommend complete transection of the diverticular
      septum in one procedure, systemic antibiotic treatment and exclusion of transoral
      intake for minimally 5 days, and contrast oesophagogram before resumption of oral
      intake to exclude fistula. Open diverticulectomy should be reserved for cases
      with inadequate endoscopic exposure and for revision surgery for multiple
      recurrences from endoscopic diverticulotomies. 

PMID- 24729974
TI  - Noncoding RNAs: emerging players in muscular dystrophies.
AB  - The fascinating world of noncoding RNAs has recently come to light, thanks to the
      development of powerful sequencing technologies, revealing a variety of RNA
      molecules playing important regulatory functions in most, if not all, cellular
      processes. Many noncoding RNAs have been implicated in regulatory networks that
      are determinant for skeletal muscle differentiation and disease. In this review,
      we outline the noncoding RNAs involved in physiological mechanisms of myogenesis
      and those that appear dysregulated in muscle dystrophies, also discussing their
      potential use as disease biomarkers and therapeutic targets. 

PMID- 24729977
TI  - Advance health care directives and "public guardian": the Italian supreme court
      requests the status of current and not future inability.
AB  - Advance health care decisions animate an intense debate in several European
      countries, which started more than 20 years ago in the USA and led to the
      adoption of different rules, based on the diverse legal, sociocultural and
      philosophical traditions of each society. In Italy, the controversial issue of
      advance directives and end of life's rights, in the absence of a clear and
      comprehensive legislation, has been over time a subject of interest of the
      Supreme Court. Since 2004 a law introduced the "Public Guardian," aiming to
      provide an instrument of assistance to the person lacking in autonomy because of
      an illness or incapacity. Recently, this critical issue has once again been
      brought to the interest of the Supreme Court, which passed a judgment trying to
      clarify the legislative application of the appointment of the Guardian in the
      field of advance directives. 

PMID- 24729976
TI  - PPAR- gamma impairment alters peroxisome functionality in primary astrocyte cell
      cultures.
AB  - Peroxisomes provide glial cells with protective functions against the harmful
      effects of H2O2 on neurons and peroxisome impairment results in nervous lesions.
      Agonists of the gamma -subtype of the Peroxisome-Proliferator-Activated-Receptors
      (PPAR) have been proposed as neuroprotective agents in neurodegenerative
      disorders. Nevertheless, the role of PPAR- gamma alterations in
      pathophysiological mechanisms and the relevance of peroxisome functions in the
      PPAR- gamma effects are not yet clear. In a primary cell culture of rat
      astrocytes, the irreversible PPAR- gamma antagonist GW9662 concentration
      dependently decreased the activity of catalase, the most important antioxidant
      defense enzyme in peroxisomes. Catalase functionality recovered in a few days and
      the PPAR- gamma agonist rosiglitazone promoted reversal of enzymatic damage. The
      reversible antagonist G3335 reduced both the activity and expression of catalase
      in a rosiglitazone-prevented manner. G3335 reduced also the glutathione reductase
      expression, indicating that enzyme involved in glutathione regeneration was
      compromised. Neither the PPAR- alpha target gene Acyl-Coenzyme-A-oxidase-1 nor
      the mitochondrial detoxifying enzyme NADH:ubiquinone-oxidoreductase (NDFUS3) was
      altered by PPAR- gamma inhibition. In conclusion, PPAR- gamma inhibition induced
      impairment of catalase in astrocytes. A general decrease of the antioxidant
      defenses of the cell suggests that a PPAR- gamma hypofunction could participate
      in neurodegenerative mechanisms through peroxisomal damage. This series of
      experiments could be a useful model for studying compounds able to restore
      peroxisome functionality. 

PMID- 24729978
TI  - Hypoxia-induced endothelial damage and microthrombosis in myocardial vessels of
      newborn landrace/large white piglets.
AB  - OBJECTIVE: Evaluating the presence of endothelial changes in myocardial vessels
      in an experimental model of hypoxia and resuscitation in newborn piglets.
      METHODS: Fifty male Landrace/Large White neonatal piglets were studied: ten of
      them were allocated in group A (control group, SHAM-operated). In group B (forty
      animals, experimental group) normocapnic hypoxia was induced by decreasing
      inspired concentration of O2 to 6%-8%. When the animals developed bradycardia or
      severe hypotension, reoxygenation was initiated. The animals of group B were
      allocated in 4 subgroups of 10, according to the concentration of O2 they were
      resuscitated with (groups 1, 2, 3, and 4 received 18%, 21%, 40%, and 100% O2,
      resp.). RESULTS: Control group animals did not show any significant endothelial
      lesions. Contrarily, endothelial lesions were detected in all experimental group
      cases. When these lesions were analyzed in the different heart zones, no
      significant difference in their incidence was observed; analyzing the frequency
      in the animals of the 4 subgroups, only microthrombosis showed a higher frequency
      in animals in groups 4 and 3. CONCLUSIONS: Endothelial damage represents a
      diffuse pathological feature in the myocardial vessels of piglets subjected to
      normocapnic hypoxia and resuscitation suggesting a possible role of
      hyperoxygenation in aggravating endothelial damage.

PMID- 24729979
TI  - Treatment of Laryngoceles: what is the progress over the last two decades?
AB  - OBJECTIVES: To review surgical techniques used in the treatment of laryngoceles
      over the last two decades and point out developments and trends. MATERIALS AND
      METHODS: PubMed, the Cochrane Library, and the JBI Library of Systematic Reviews
      were searched using the term "laryngocele." Demographic data, type of
      laryngocele, presence of a laryngopyocele, type of treatment and need for a
      tracheotomy were assessed. RESULTS: Overall, data on 86 patients were analyzed,
      culled from 50 articles, of which 41 were case reports and 9 were case series. No
      single systematic review or meta-analysis or randomized controlled trial has been
      published on the topic. Altogether, 71 laryngoceles in 63 patients met the
      criteria for further analysis focusing on surgical treatment. An external
      approach was selected in 25/29 (86.2%) cases of combined laryngoceles.
      Microlaryngoscopic resection using a CO2 laser was performed in three cases and
      endoscopic robotic surgery in one case. The majority of patients with an internal
      laryngocele, 31/42 (73.8%), were treated using the microlaryngoscopy approach.
      CONCLUSIONS: Microlaryngoscopy involving the use of a CO2 laser has become the
      main therapeutic procedure for the treatment of internal laryngoceles during the
      past 20 years. An external approach still remains the main therapeutic approach
      for the treatment of combined laryngoceles.

PMID- 24729980
TI  - Polymorphisms in the RANK/RANKL genes and their effect on bone specific prognosis
      in breast cancer patients.
AB  - The receptor activator of NF-kappaB (RANK) pathway is involved in bone health as
      well as breast cancer (BC) pathogenesis and progression. Whereas the therapeutic
      implication of this pathway is established for the treatment of osteoporosis and
      bone metastases, the application in adjuvant BC is currently investigated. As
      genetic variants in this pathway have been described to influence bone health,
      aim of this study was the prognostic relevance of genetic variants in RANK and
      RANKL. Single nucleotide polymorphisms in RANK(L)
      (rs1054016/rs1805034/rs35211496) were genotyped and analyzed with regard to bone
      metastasis-free survival (BMFS), disease-free survival, and overall survival for
      a retrospective cohort of 1251 patients. Cox proportional hazard models were
      built to examine the prognostic influence in addition to commonly established
      prognostic factors. The SNP rs1054016 seems to influence BMFS. Patients with two
      minor alleles had a more favorable prognosis than patients with at least one
      common allele (HR 0.37 (95% CI: 0.17, 0.84)), whereas other outcome parameters
      remained unaffected. rs1805034 and rs35211496 had no prognostic relevance. The
      effect of rs1054016(RANKL) adds to the evidence that the RANK pathway plays a
      role in BC pathogenesis and progression with respect to BMFS, emphasizing the
      connection between BC and bone health. 

PMID- 24729981
TI  - Vancomycin-resistant Enterococcus faecium Bacteremia in a tertiary care hospital:
      epidemiology, antimicrobial susceptibility, and outcome.
AB  - Vancomycin-resistant Enterococcus faecium (VREF) has emerged as a relevant
      multidrug-resistant pathogen and potentially lethal etiology of health care
      associated infections worldwide. The objective of this retrospective cohort study
      was to assess factors associated with mortality in patients with VREF bacteremia
      in a major tertiary referral hospital in Southern Brazil. All documented cases of
      bacteremia identified between May 2010 and July 2012 were evaluated. Cox
      regression was performed to determine whether the characteristics related to the
      host or antimicrobial treatment were associated with the all-cause 30-day
      mortality. In total, 35 patients with documented VREF bacteremia were identified
      during the study period. The median APACHE-II score of the study population was
      26 (interquartile range: 10). The overall 30-day mortality was 65.7%. All VREF
      isolates were sensitive to linezolid, daptomycin, and quinupristin-dalfopristin.
      Linezolid was the only antimicrobial agent with in vitro activity against VREF
      that was administered to the cohort. After multivariate analysis, linezolid
      treatment (HR, 0.08; 95% CI, 0.02-0.27) and presence of acute kidney injury at
      the onset of bacteremia (HR, 4.01; 95% CI, 1.62-9.94) were independently
      associated with mortality. Presentation with acute kidney injury and lack of
      treatment with an effective antibiotic poses risk for mortality in patients with
      VREF bacteremia. 

PMID- 24729982
TI  - Differences in the alveolar macrophage proteome in transgenic mice expressing
      human SP-A1 and SP-A2.
AB  - Surfactant protein A (SP-A) plays a number of roles in lung host defense and
      innate immunity. There are two human genes, SFTPA1 and SFTPA2, and evidence
      indicates that the function of SP-A1 and SP-A2 proteins differ in several
      respects. To investigate the impact of SP-A1 and SP-A2 on the alveolar macrophage
      (AM) phenotype, we generated humanized transgenic (hTG) mice on the SP-A knockout
      (KO) background, each expressing human SP-A1 or SP-A2. Using two-dimensional
      difference gel electrophoresis (2D-DIGE) we studied the AM cellular proteome. We
      compared mouse lines expressing high levels of SPA1, high levels of SP-A2, low
      levels of SP-A1, and low levels of SP-A2, with wild type (WT) and SP-A KO mice.
      AM from mice expressing high levels of SP-A2 were the most similar to WT mice,
      particularly for proteins related to actin and the cytoskeleton, as well as
      proteins regulated by Nrf2. The expression patterns from mouse lines expressing
      higher levels of the transgenes were almost the inverse of one another - the most
      highly expressed proteins in SP-A2 exhibited the lowest levels in the SP-A1 mice
      and vice versa. The mouse lines where each expressed low levels of SP-A1 or SP-A2
      transgene had very similar protein expression patterns suggesting that responses
      to low levels of SP-A are independent of SP-A genotype, whereas the responses to
      higher amounts of SP-A are genotype-dependent. Together these observations
      indicate that in vivo exposure to SP-A1 or SP-A2 differentially affects the
      proteomic expression of AMs, with SP-A2 being more similar to WT.

PMID- 24729983
TI  - Multimodal MRI-based Imputation of the Abeta+ in Early Mild Cognitive Impairment.
AB  - OBJECTIVE: To identify brain atrophy from structural-MRI and cerebral blood
      flow(CBF) patterns from arterial spin labeling perfusion-MRI that are best
      predictors of the Abeta-burden, measured as composite 18F-AV45-PET uptake, in
      individuals with early mild cognitive impairment(MCI). Furthermore, to assess the
      relative importance of imaging modalities in classification of Abeta+/Abeta-
      early mild cognitive impairment. METHODS: Sixty-seven ADNI-GO/2 participants with
      early-MCI were included. Voxel-wise anatomical shape variation measures were
      computed by estimating the initial diffeomorphic mapping momenta from an unbiased
      control template. CBF measures normalized to average motor cortex CBF were mapped
      onto the template space. Using partial least squares regression, we identified
      the structural and CBF signatures of Abeta after accounting for normal cofounding
      effects of age, sex, and education. RESULTS: 18F-AV45-positive early-MCIs could
      be identified with 83% classification accuracy, 87% positive predictive value,
      and 84% negative predictive value by multidisciplinary classifiers combining
      demographics data, ApoE epsilon4-genotype, and a multimodal MRI-based Abeta
      score. INTERPRETATION: Multimodal-MRI can be used to predict the amyloid status
      of early-MCI individuals. MRI is a very attractive candidate for the
      identification of inexpensive and non-invasive surrogate biomarkers of Abeta
      deposition. Our approach is expected to have value for the identification of
      individuals likely to be Abeta+ in circumstances where cost or logistical
      problems prevent Abeta detection using cerebrospinal fluid analysis or Abeta-PET.
      This can also be used in clinical settings and clinical trials, aiding subject
      recruitment and evaluation of treatment efficacy. Imputation of the Abeta
      positivity status could also complement Abeta-PET by identifying individuals who
      would benefit the most from this assessment.

PMID- 24729984
TI  - Variation in Mu-Opioid Receptor Gene (OPRM1) as a Moderator of Naltrexone
      Treatment to Reduce Heavy Drinking in a High Functioning Cohort.
AB  - BACKGROUND: It is well known that naltrexone, an FDA-approved medication for
      treatment of alcohol dependence, is effective for only a subset of individuals.
      Recent studies have examined the utility of a functional A118G single nucleotide
      polymorphism (SNP) of the mu-opioid receptor gene (OPRM1) as a predictor of
      naltrexone treatment response. Although the findings to date have generally been
      consistent with a moderating effect of the SNP, further evaluation of this
      hypothesis is warranted. OBJECTIVE: To evaluate whether problem drinkers with one
      or two copies of the 118G allele respond better to naltrexone treatment. The
      treatment goal in this cohort of high functioning men who have sex with men (MSM)
      was to reduce heavy drinking, rather than to promote abstinence. METHOD: 112
      subjects of European ancestry from a randomized clinical trial of naltrexone and
      behavioral therapy for problem drinking MSM were included in the analysis.
      Subjects were treated for 12 weeks with 100 mg/day of oral naltrexone
      hydrochloride. All participants received medical management with a modified
      version of the Brief Behavioral Compliance Enhancement Treatment (BBCET), alone
      or in combination with Modified Behavioral Self-control Therapy (MBSCT). RESULTS:
      Naltrexone-treated subjects with one or two 118G alleles had a significantly
      greater percentage of non-hazardous drinking (NoH) (p < 0.01) than those treated
      with placebo or A118 homozygotes in either medication group. CONCLUSIONS: These
      results are consistent with a modest moderating effect of the OPRM1 118G allele
      on the reduction of heavy drinking by naltrexone treatment.

PMID- 24729986
TI  - Automatic Parameterization Strategy for Cardiac Electrophysiology Simulations.
AB  - Driven by recent advances in medical imaging, image segmentation and numerical
      techniques, computer models of ventricular electrophysiology account for
      increasingly finer levels of anatomical and biophysical detail. However,
      considering the large number of model parameters involved parameterization poses
      a major challenge. A minimum requirement in combined experimental and modeling
      studies is to achieve good agreement in activation and repolarization sequences
      between model and experiment or patient data. In this study, we propose basic
      techniques which aid in determining bidomain parameters to match activation
      sequences. An iterative parameterization algorithm is implemented which
      determines appropriate bulk conductivities which yield prescribed velocities. In
      addition, a method is proposed for splitting the computed bulk conductivities
      into individual bidomain conductivities by prescribing anisotropy ratios.

PMID- 24729985
TI  - Bilateral Synergy: A Framework for Post-Stroke Rehabilitation.
AB  - BACKGROUND: Unilateral stroke produces debilitating deficits in voluntary control
      in the contralesional arm, and significant motor coordination deficits in the
      ipsilesional arm. In addition, patients tend to avoid bilateral arm patterns and
      during performance of activities of daily living. Nevertheless, upper extremity
      physical rehabilitation predominantly focuses on motor training activities with
      only the paretic arm. This can be limiting because of persistent deficits in the
      ipsilesional arm, and because of the tendency of patients to avoid spontaneous
      bilateral arm patterns. PROPOSITION: Rehabilitation should focus on bilateral
      training to advance recovery of function in both arms of stroke patients, as well
      as to facilitate spontaneous bilateral arm use. This paper reviews the rationale
      for this approach, citing evidence for significant hemisphere specific bilateral
      motor deficits in stroke patients, which affect both the contralesional and the
      ipsilesional arm. The rationale for, and advantages of, training both arms
      simultaneously through bilateral tasks is reviewed. Although bilateral training
      has been employed to treat stroke patients previously, this has tended to focus
      on bimanual 'coupling' as a rationale for performing parallel, but not
      cooperative bilateral tasks. Bilateral synergy provides a more functional
      framework for structuring post-stroke upper extremity rehabilitation. CONCLUSION:
      Bilateral synergy may be causally linked to spontaneous bilateral arm use,
      suggesting that rehabilitation should be focused on bilateral cooperative tasks,
      such as bilateral object transport. Further research is required to determine
      whether this approach could be efficacious for patients with hemiparesis, and
      whether both left and right hemisphere strokes can benefit from such
      intervention.

PMID- 24729987
TI  - H63D genotying for hemochromatosis: helper or hindrance?

PMID- 24729988
TI  - Groove pancreatitis: a common condition that is uncommonly diagnosed
      preoperatively.

PMID- 24729989
TI  - Benign tailgut cyst masquerading as a hemorrhoid.

PMID- 24729990
TI  - The trientine crisis in Canada: a call to advocacy.

PMID- 24729991
TI  - Practice and documentation of performance of colonoscopy in a central Canadian
      health region.
AB  - OBJECTIVE: To evaluate the reporting and performance of colonoscopy in a large
      urban centre. METHODS: Colonoscopies performed between January and April 2008 in
      community hospitals and academic centres in the Winnipeg Regional Health
      Authority (Manitoba) were identified from hospital discharge databases and
      retrospective review of a random sample of identified charts. Information
      regarding reporting of colonoscopies (including bowel preparation,
      photodocumentation of cecum/ileum, size, site, characteristics and method of
      polyp removal), colonoscopy completion rates and follow-up recommendations was
      extracted. Colonoscopy completion rates were compared among different groups of
      physicians. RESULTS: A total of 797 colonoscopies were evaluated. Several
      deficiencies in reporting were identified. For example, bowel preparation quality
      was reported in only 20%, the agent used for bowel preparation was recorded in
      50%, photodocumentation of colonoscopy completion in 6% and polyp appearance (ie,
      pedunculated or not) in 34%, and polyp size in 66%. Although the overall
      colonoscopy completion rate was 92%, there was a significant difference among
      physicians with varying medical specialty training and volume of procedures
      performed. Recommendations for follow-up procedures (barium enema, computed
      tomography colonography or repeat colonoscopy) were recorded for a minority of
      individuals with reported poor bowel preparation or incomplete colonoscopy.
      CONCLUSIONS: The present study found many deficiencies in reporting of
      colonoscopy in typical, city-wide clinical practices. Colonoscopy completion
      rates varied among different physician specialties. There is an urgent need to
      adopt standardized colonoscopy reporting systems in everyday practice and to
      provide feedback to physicians regarding deficiencies so they can be rectified.

PMID- 24729992
TI  - Geographical variation and factors associated with colorectal cancer mortality in
      a universal health care system.
AB  - OBJECTIVE: To investigate the geographical variation and small geographical area
      level factors associated with colorectal cancer (CRC) mortality. METHODS:
      Information regarding CRC mortality was obtained from the population-based
      Manitoba Cancer Registry, population counts were obtained from Manitoba's
      universal health care plan Registry and characteristics of the area of residence
      were obtained from the 2001 Canadian census. Bayesian spatial Poisson mixed
      models were used to evaluate the geographical variation of CRC mortality and
      Poisson regression models for determining associations with CRC mortality. Time
      trends of CRC mortality according to income group were plotted using joinpoint
      regression. RESULTS: The southeast (mortality rate ratio [MRR] 1.31 [95% CI 1.12
      to 1.54) and southcentral (MRR 1.62 [95% CI 1.35 to 1.92]) regions of Manitoba
      had higher CRC mortality rates than suburban Winnipeg (Manitoba's capital city).
      Between 1985 and 1996, CRC mortality did not vary according to household income;
      however, between 1997 and 2009, individuals residing in the highest-income areas
      were less likely to die from CRC (MRR 0.77 [95% CI 0.65 to 0.89]). Divergence in
      CRC mortality among individuals residing in different income areas increased over
      time, with rising CRC mortality observed in the lowest income areas and declining
      CRC mortality observed in the higher income areas. CONCLUSIONS: Individuals
      residing in lower income neighbourhoods experienced rising CRC mortality despite
      residing in a jurisdiction with universal health care and should receive
      increased efforts to reduce CRC mortality. These findings should be of particular
      interest to the provincial CRC screening programs, which may be able to reduce
      the disparities in CRC mortality by reducing the disparities in CRC screening
      participation.

PMID- 24729993
TI  - Iron overload is rare in patients homozygous for the H63D mutation.
AB  - BACKGROUND: Previous research has suggested that the H63D HFE mutation is
      associated with elevated iron indexes. However, the true penetrance of this
      mutation remains unclear. OBJECTIVE: To assess the proportion of H63D homozygotes
      with laboratory abnormalities consistent with iron overload. METHODS: The present
      study was a retrospective analysis of all individuals referred for HFE genotyping
      in Newfoundland and Labrador between 1999 and 2009, who were found to be
      homozygous for the H63D mutation. Using electronic health records, results of
      ferritin, transferrin saturation, aspartate aminotransferase and alanine
      aminotransferase testing performed closest to the time of genetic testing were
      recorded for each patient. Iron overload was classified using previously
      published definitions from the HealthIron study. SPSS version 17.0 (IBM
      Corporation, USA) was used for descriptive statistics and to compare means using
      one-way ANOVA. RESULTS: Between 1999 and 2009, 170 individuals tested positive
      for H63D/H63D. At the time of genotyping, 28.8% had an elevated mean (+/- SD)
      ferritin level of 501+/-829 MUg/L and 15.9% had an elevated transferrin
      saturation of 0.45+/-0.18. At genotyping, 94 individuals had sufficient data
      available to classify iron overload status. Only three (3.2%) had documented iron
      overload while the majority (85.1%) had no evidence of iron overload. Sixty
      individuals had follow-up data available and, of these, only four (6.7%) had
      documented iron overload, while 45 (75.0%) had no evidence of iron overload. Only
      one individual had evidence of iron overload-related disease at genotyping and at
      follow-up. CONCLUSIONS: H63D homozygosity was associated with an elevated mean
      ferritin level, but only 6.7% had documented iron overload at follow-up. The
      penetrance of the H63D mutation appeared to be low.

PMID- 24729994
TI  - Computer-based virtual reality colonoscopy simulation improves patient-based
      colonoscopy performance.
AB  - BACKGROUND: Colonoscopy simulators that enable one to perform computer-based
      virtual colonoscopy now exist. However, data regarding the effectiveness of this
      virtual training are limited. OBJECTIVE: To determine whether virtual reality
      simulator training translates into improved patient-based colonoscopy
      performance. METHODS: The present study was a prospective controlled trial
      involving 18 residents between postgraduate years 2 and 4 with no previous
      colonoscopy experience. These residents were assigned to receive 16 h of virtual
      reality simulator training or no training. Both groups were evaluated on their
      first five patient-based colonoscopies. The primary outcome was the number of
      proctor 'assists' required per colonoscopy. Secondary outcomes included insertion
      time, depth of insertion, cecal intubation rate, proctor- and nurse-rated
      competence, and patient-rated pain. RESULTS: The simulator group required
      significantly fewer proctor assists than the control group (1.94 versus 3.43; P
      <= 0.001), inserted the colonoscope further unassisted (43 cm versus 24 cm;
      P=0.003) and there was a trend to intubate the cecum more often (26% versus 10%;
      P=0.06). The simulator group received higher ratings of competence from both the
      proctors (2.28 versus 1.88 of 5; P=0.02) and the endoscopy nurses (2.56 versus
      2.05 of 5; P=0.001). There were no significant differences in proctor-, nurse- or
      patient-rated pain, or attention to discomfort. CONCLULSIONS: Computer-based
      colonoscopy simulation in the initial stages of training improved novice
      trainees' patient-based colonoscopy performance.

PMID- 24729995
TI  - Initial management of noncirrhotic splanchnic vein thrombosis: when is
      anticoagulation enough?
AB  - BACKGROUND: The optimal initial treatment of splanchnic vein thrombosis is
      uncertain. Anticoagulant therapy has been shown to be associated with vessel
      recanalization and decreased recurrence. Furthermore, information regarding
      potential predictors of chronic complications is not well understood. METHODS: A
      retrospective cohort study involving consecutive patients diagnosed with first
      episode noncirrhotic splanchnic vein thrombosis referred to the thrombosis clinic
      of the authors' institution between 2008 and 2011 was conducted. Demographic and
      clinical information was collected. The response to initial anticoagulant therapy
      was evaluated by determining radiographic recanalization of vessels and clinical
      resolution (defined as the absence of ongoing splanchnic vein thrombosis symptoms
      or complications requiring treatment beyond anticoagulant therapy). RESULTS:
      Twenty-two patients were included. Anticoagulant therapy alone resulted in vessel
      recanalization in 41% of patients and 68% achieved clinical resolution. Two
      patients experienced bleeding events. Factors associated with a lack of clinical
      resolution included signs of portal hypertension/liver failure on presentation,
      complete vessel occlusion at diagnosis, presence of a myeloproliferative disorder
      or JAK2V617F tyrosine kinase mutation and the absence of a local/transient
      predisposing factor. CONCLUSIONS: Anticoagulant therapy appeared to be an
      effective initial treatment in patients with splanchnic vein thrombosis. Clinical
      factors may help to identify patients who are at risk for developing
      complications thus requiring closer monitoring. These findings were limited by
      the small sample size and need to be explored in larger prospective studies.

PMID- 24729996
TI  - Care of the liver transplant patient.
AB  - OBJECTIVE: To provide an approach to the care of liver transplant (LT) patients,
      a growing patient population with unique needs. METHODS: A literature search of
      PubMed for guidelines and review articles using the keywords "liver
      transplantation", "long term complications" and "medical management" was
      conducted, resulting in 77 articles. RESULTS: As a result of being on
      immunosuppression, LT recipients are at increased risk of infections and must be
      screened regularly for metabolic complications and malignancies. DISCUSSION:
      Although immunosuppression is key to maintaining allograft health after
      transplantation, it comes with its own set of medical issues to follow.
      Physicians following LT recipients must be aware of the greater risk for
      hypertension, diabetes, dyslipidemia, renal failure, metabolic bone disease and
      malignancies in these patients, all of whom require regular monitoring and
      screening. Vaccination, quality of life, sexual function and pregnancy must be
      specifically addressed in transplant patients.

PMID- 24729997
TI  - Registered nurse-performed flexible sigmoidoscopy in Ontario.

PMID- 24729998
TI  - A care coordination program to optimize management of cirrhosis: real-life
      applicability and feasibility in the context of the Canadian health care system.

PMID- 24729999
TI  - When orthopedic physicians become employees.

PMID- 24730000
TI  - Effect of capsulotomy on hip stability-a consideration during hip arthroscopy.
AB  - We conducted a study to further understand the effect of capsulotomy on hip joint
      stability using an in vitro cadaver model. Thirteen fresh-frozen cadaveric hip
      specimens were subjected to an external rotation torque of 0.588 Nm. The
      experimental kinematics, post-process translation, and rotation data for each
      specimen were tested under 4 conditions: neutral flexion with capsule intact;
      neutral flexion with transverse capsulotomy; maximum flexion with capsule intact;
      and maximum flexion with transverse capsulotomy. A segmented 3-dimensional model
      of the femur was used to evaluate femoral head translation after application of
      external rotation torque. In maximum flexion, hips with intact capsules rotated
      less than hips with capsulotomy in the y (abduction) and z (external rotation)
      planes (y-plane, P = .01; z-plane, P = .02). After capsulotomy, there was a
      qualitative observation of increased distal, lateral, and anterior translation of
      the femoral head in neutral position, and a qualitative observation of increased
      medial, posterior, and distal translation of the femoral head in flexion.
      Qualitatively, after capsulotomy, hips tested in neutral position demonstrated
      more translation than rotation, whereas hips tested in flexion demonstrated more
      rotation than translation. Capsulotomy appears to permit increased rotation in
      maximum flexion. Hips tested in neutral trended toward more translation than
      rotation, whereas hips in flexion trended toward more rotation than translation.
      Judicious capsular management is indicated during arthroscopic hip procedures.

PMID- 24730001
TI  - Nationwide trends in total shoulder arthroplasty and hemiarthroplasty for
      osteoarthritis.
AB  - Recent literature reports an increase in the rate of shoulder arthroplasties,
      particularly total shoulder arthroplasties (TSAs), being performed in the United
      States. However, the national epidemiology of use of hemiarthroplasty (HA) and
      TSA as treatments for glenohumeral osteoarthritis has not been elucidated. We
      conducted a study to analyze trends in using HA and TSA as treatments for
      glenohumeral osteoarthritis from 2000 to 2010, and to compare patient
      characteristics and inpatient complications. US Nationwide Inpatient Sample
      patients with a primary inpatient diagnosis of shoulder arthritis and a principal
      procedure of HA or TSA were identified using International Classification of
      Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) procedural codes. From
      2000 to 2010 the nationally adjusted population rate of shoulder arthroplasty
      performed for osteoarthritis increased 3.7-fold. Specifically, the population
      rate of TSA increased 5.0-fold, and that of HA increased 1.9-fold. In 2010, 80.3%
      of patients having shoulder arthroplasty for arthritis underwent TSA. TSA
      patients were older (P < .0001) and had a higher mean number of chronic illnesses
      (P = .034). TSA-associated discharges had a higher rate of surgical and medical
      care complications (P = .011) and blood transfusions (P = .041) after adjusting
      for comorbidities.

PMID- 24730002
TI  - Acute compartment syndrome in patients with tibia fractures transferred for
      definitive fracture care.
AB  - We sought to determine if patients evaluated at an outside institution for a
      tibia fracture and transferred to a referral hospital for fracture management
      were at risk for having acute compartment syndrome (ACS) on arrival. We conducted
      a database search for cases in which patients were referred for definitive
      fixation of tibia fractures, and on initial evaluation at our institution were
      diagnosed with ACS that necessitated fasciotomy. Incidence, demographics,
      fracture type, early complications, and factors that predict ACS were evaluated.
      Between 1996 and 2008, 9 patients (6 men, 3 women; mean age, 44.4 years) were
      transferred for definitive fixation of a tibia fracture and on presentation had
      ACS of the involved extremity (1.0% of all tibia fractures treated during this
      period). Two of the 9 patients developed contractures. Seven of the 9 patients
      had a good clinical result, and there were no amputations. There is increased
      risk for ACS in all patients with musculoskeletal trauma, irrespective of age,
      sex, fracture type, or injury mechanism. Given this risk, physicians must closely
      monitor patients. A patient should not be transferred until a fasciotomy is
      performed, if there is a significant risk of developing compartment syndrome
      prior to or during transport.

PMID- 24730003
TI  - A multidisciplinary total hip arthroplasty protocol with accelerated
      postoperative rehabilitation: does the patient benefit?
AB  - Since its debut over 10 years ago, minimally invasive total hip arthroplasty
      (THA) has often been associated with accelerated postoperative rehabilitation
      when compared with THA performed with a traditional surgical approach. The
      objective of this study was to investigate the effect of accelerated
      postoperative rehabilitation and early mobilization on length of stay and
      hospital readmissions in patients undergoing THA at one institution. We
      retrospectively reviewed a consecutive series of 590 patients who underwent THA
      between January 31, 2011 and April 30, 2011. Six arthroplasty surgeons using
      varying surgical techniques participated. One hundred ninety patients received
      accelerated rehabilitation and were mobilized on the day of surgery. The
      remaining 400 patients were mobilized on postoperative day one (POD1). Length of
      stay for the accelerated rehabilitation group was 2.06 days and 3.38 days for the
      standard group. One patient was readmitted to the hospital within 30 days (.52%)
      in the accelerated group compared to 19 re-hospitalizations (4.72%) in the POD1
      group. Ninety-six percent of the accelerated group were discharged home versus
      62% in POD1 group. Our results support the use of an accelerated rehabilitation
      protocol at one institution following total hip replacement surgery.

PMID- 24730004
TI  - Iatrogenic transection of the peroneal and partial transection of the tibial
      nerve during arthroscopic lateral meniscal debridement and removal of
      osteochondral fragment.
AB  - Knee arthroscopy is a common orthopedic procedure that is generally considered
      relatively safe, with overall complication rates reported between 1% and 8%.
      Approximately 0.01% to 0.06% of these complications involve neurovascular
      structures. While peroneal nerve and tibial artery complications are well
      reported, to our knowledge, injury to the tibial nerve has not been reported. We
      report a case of injury to the tibial and peroneal nerves during routine meniscal
      debridement and osteochondral fragment removal in a 17-year-old high school
      athlete. The likely mechanism of injury was violation of the posterolateral
      corner by powered arthroscopic instrumentation during the attempt at removal of
      the loose body. The peroneal nerve was repaired with an interpositional sural
      nerve graft. Management of these injuries should consist of following patients
      closely with electromyograms and nerve exploration and repair in those cases that
      do not show interval improvement. Clinicians should exercise extreme care while
      using powered instruments in the posterolateral corner.

PMID- 24730005
TI  - Orthopedic management of complications of using intraosseous catheters.
AB  - Intraosseous (IO) catheters have been used for vascular access in trauma and
      critically ill patients with increasing frequency in emergency departments and
      critical care units across the United States. Their use has long been accepted as
      a reliable method of obtaining vascular access in pediatric patients with
      difficult intravascular access. Articles about the complications of using IO
      catheters are scarce. Although orthopedic surgeons are not likely to place an IO
      catheter in an emergency situation, they often become involved when complications
      of IO catheter use arise. In a literature search, we identified 5,759 patients
      treated with IO catheters. The overall complication rate was 2.1%. In this
      article, we discuss the literature on IO catheter complications and report 2
      cases of orthopedic management of IO catheter complications.

PMID- 24730006
TI  - Readability of sports medicine-related patient education materials from the
      American Academy of Orthopaedic Surgeons and the American Orthopaedic Society for
      Sports Medicine.
AB  - Although studies have revealed high readability levels of orthopedic patient
      education materials, no study has evaluated sports medicine-related patient
      education materials. We conducted a study to assess the readability of sports
      medicine-related patient education materials from the American Academy of
      Orthopaedic Surgeons (AAOS) and the American Orthopaedic Society for Sports
      Medicine (AOSSM). All sports medicine patient education articles available online
      in 2012 from the AAOS and the AOSSM, including the Stop Sports Injuries Campaign
      (STOP), were identified, and their readability was assessed with the Flesch
      Kinkaid (FK) readability test. Mean overall FK grade level of the 170 articles
      reviewed (104 from AAOS, 36 from AOSSM, 30 from STOP) was 10.2. Mean FK levels
      for the 3 sources were 9.5 (AAOS), 11.0 (AOSSM), and 11.5 (STOP) (P = .16).
      Fifteen (8.8%) of the 170 articles had a readability level at or below eighth
      grade (average reading level of US adults); only 2 (1.2%) of the 170 articles
      were at or below the recommended sixth-grade level. The majority of sports
      medicine-related patient education materials from AAOS and AOSSM had reading
      levels higher than recommended, indicating that the majority of the patient
      population may find it difficult to comprehend these articles.

PMID- 24730007
TI  - Hyponatremia after primary hip and knee arthroplasty: incidence and associated
      risk factors.
AB  - Hyponatremia is the most common electrolyte abnormality in clinical practice.
      Often overlooked or misdiagnosed, hyponatremia can quickly deteriorate and cause
      serious and potentially life-threatening complications. In the orthopedic
      patient, hyponatremia can mimic common postoperative sequelae, thereby making
      diagnosis even more difficult. Although serious complications of hyponatremia are
      rare, they are severe, and early detection is crucial in initiating prompt
      treatment. From 2008 to 2010, 392 consecutive hip and knee arthroplasties were
      prospectively monitored for development of hyponatremia. Hyponatremia occurred in
      155 (40%) of cases. Although the majority were mild, 7% were moderate or severe
      deficiencies, which are associated with increased morbidity. Risk factors
      included preoperative hyponatremia, female sex, older age, lower body weight,
      knee more than hip surgery, and bilateral knee arthroplasty. Thiazides and
      angiotensin-converting enzyme inhibitors were the only medications associated
      with low postoperative sodium values. Hyponatremia is common after elective
      orthopedic surgery and is associated with identifiable perioperative risk
      factors. Although the most severe complications are rare, failure to identify
      mild cases of hyponatremia allows the sodium deficit to worsen unnecessarily.
      Early detection is important because, unlike severe cases, mild hyponatremia is
      generally treatable with simple medical management.

PMID- 24730008
TI  - Intrathoracic fracture-dislocation of the proximal humerus treated with rib
      fixation and shoulder arthroplasty.
AB  - Proximal fractures of the humerus resulting in intrathoracic displacement of the
      humeral head are rare, but cause serious pain and can lead to pulmonary and
      glenohumeral complications. Many treatment options exist, but there is still no
      literature regarding mortality and morbidity associated with rib fixation in
      concordance with treatment of the proximal humerus. This case describes a patient
      who was treated using a multi-team approach that involved shoulder arthroplasty
      with rib fixation, and which resulted in decreased pain and decreased narcotic
      use while improving the patient's pulmonary function.

PMID- 24730009
TI  - Total hip and knee replacement in a patient with arthrogryposis multiplex
      congenita.
AB  - Arthrogryposis multiplex congenita (AMC) is a complex disorder that leads to
      joint stiffness and deformities in 2 or more joints in afflicted children. Late
      manifestations of this disorder can include secondary degeneration of the
      abnormal joints with arthritic symptoms of pain and loss of function. There are
      few reports in the orthopedic literature on the use of total joint arthroplasty
      to improve the pain and function in patients with arthrogryposis. This case
      report presents one patient who underwent bilateral total hip and total knee
      arthroplasties for deteriorating function and pain in her hips and knees
      secondary to the congenital deformities created by arthrogryposis multiplex
      congenita. We discuss the intraoperative difficulties and techniques used to
      reconstruct her hips and knees, as well as the potential indications for joint
      arthroplasty in this challenging group of patients.

PMID- 24730010
TI  - Quadriceps and patellar tendon pie-crusting as a treatment for limited flexion in
      total knee arthroplasty.
AB  - The pie-crusting method of ligament and tendon lengthening has been used
      successfully in various tissues but is not reported in the literature as an
      option for patellar or quadriceps tendons to address flexion limitation. Our case
      report discusses a patient with longstanding flexion limitation who underwent
      primary total knee arthroplasty. The report reviews the literature on
      intraoperative treatments, which primarily pertains to the condition of patella
      baja, and demonstrates that the pie-crusting technique should be included as a
      treatment option for a tight extensor mechanism while having some advantages over
      tibial tubercle osteotomy or Z-plasty.

PMID- 24730011
TI  - [A new paradigm of Cardio-Thoracic and Vascular Surgery: some historical aspects
      and evolution].

PMID- 24730012
TI  - [Vascular Surgery education and training: contemporary challenges].

PMID- 24730014
TI  - [Surgical treatment of a complete aortic arch interruption].
AB  - We describe the clinical case of a 48-year-old woman referred to our centre due
      to a recently diagnosed severe symptomatic aortic stenosis. Her past medical
      history included arterial hypertension diagnosed when she was eighteen years old.
      On preoperative study a complete interruption of the aortic arch was found,
      distal to the origin of the left subclavian artery. The patient underwent
      successful two-stage surgical correction by repair of the aortic interruption
      followed by aortic valve replacement. 

PMID- 24730015
TI  - [The role of percutaneous renal fenestration in the management of acute aortic
      dissection. Case report].
AB  - Aortic dissection is one of the most feared vascular disease, coursing with high
      rate of complications. Depending on the location of the intimal tear, aortic
      dissection could implicate the ascending aorta, the heart and descending aorta,
      or only the descending aorta. The first case (type A) has absolute surgical
      indication. Independently of a good surgical result, vascular complications may
      occur, such as arterial renal compression, associated with flow disturbances to
      these organs. Percutaneous fenestration has been proven as a good solution in
      selected patients, in experienced hands. We present a case in which the
      percutaneous technique was successfully used. 

PMID- 24730013
TI  - [Influence of processed EEG monitoring in the anesthetic management and its cost
      in off-pump coronary surgery: a research protocol].
AB  - BACKGROUD: Although in some studies intraoperative processed EEG monitoring has
      shown advantages such as less use of hypnotic drugs and decrease duration of both
      anesthetic emergency and recovery times, there is controversy on the incidence of
      awareness. It has not been demonstrated that this type of monitoring interferes
      with length of hospital stay, morbidity and mortality. Processed EEG monitoring,
      such as the bispectral index (BIS) has been widely accepted in assessing
      anesthetic depth, yet its usage is not part of the standard monitoring of the
      American Society of Anesthesiologiy (ASA). Other forms of monitoring anesthetic
      depth widely used are clinical monitoring associated with monitoring expiratory
      fraction of halogenated anesthetic agents. METHODOLOGY: Prospective randomized
      study comparing two groups of patients undergoing coronary artery bypass surgery
      without cardiopulmonary bypass (CPB): group A - BIS visible (BIS value is shown
      throughout the procedure) and group B - BIS not visible (BIS is hidden and
      monitoring of anesthetic depth is based on clinical signs associated with the
      monitoring of expiratory fraction of halogenated anesthetic agent). The aim of
      this study is to verify the existence of differences in anesthetic depth and
      associated costs in the two group study's and also to add evidence to anesthetic
      depth monitoring in an area where few studies have been done - cardiac surgery.

PMID- 24730016
TI  - Thoracoscopic removal of an intrathoracic Kirschner wire. Case report.
AB  - We report the clinical case of a clinical case of a 50-year-old woman who had a
      very rare complication related to the insertion of Kirschner wires for fixation
      of a left humerus fracture. Sixteen years after the placement of the Kirschner
      wires, a routine chest X-ray revealed that one of the Kirschner wires had
      migrated through the pleural cavity. Chest computed tomographic scans confirmed
      the presence of a metallic wire inside the left lung parenchyma, adjacent to the
      superior pulmonary artery. This particular case was managed through a video
      assisted thoracoscopic approach, and the wire was easily removed from the pleural
      cavity, thereby avoiding the need of a thoracotomy. 

PMID- 24730017
TI  - [Reconstructive surgery of the large intrathoracic veins, four case reports].
AB  - The resection and reconstruction of the large venous vessels of the chest is a
      procedure intended to treat the symptoms of venous hypertension caused by the
      Superior Vena Cava Syndrome and to allow resection of mediastinal tumors that
      invade the superior vena cava (SVC) and the left and right innominate veins. We
      report four clinical cases of mediastinal tumors involving the large
      intrathoracic venous vessels, submitted to surgery between 2010 and 2013. In all
      cases our purpose was to completely resect the tumor. We intended to evaluate the
      surgical results in terms of improvement of symptoms, complications of the
      procedures, permeability of the bypasses in the short and medium term and
      mortality rates. We used ringed ePTFE grafts to perform the following vascular
      reconstructions: - Y configuration bypass from the left subclavian vein and the
      left internal jugular vein to the left inominate vein; - two bypasses from the
      top of the left innominate vein to the right atrial appendage; - bypass from the
      left innominate vein to the right atrial appendage and a bypass from the right
      innominate vein to the SVC. All patients were discharged, and all the bypasses
      were patent at discharge and after 30 days . There were two cases of late
      thrombosis, but patients remained asymptomatic. Our series shows the feasibility
      of these technically complex surgeries, which are an excellent example of the
      benefits of multidisciplinary collaboration between vascular and thoracic
      surgeons.

PMID- 24730018
TI  - [Results of thrombectomy for prosthetic graft occlusion. A five-years consecutive
      experience].
AB  - OBJECTIVES: Evaluation of graft thrombectomies performed at our department,
      during a five years' consecutive period. METHODS: Charts of all consecutive graft
      thrombosis treated with surgical thrombectomy at our department between June/2006
      and September/2011 were retrospectively reviewed. Thrombectomy primary patency,
      limb salvage and mortality rates were estimated by the Kaplan-Meier method.
      Differences among subgroups were tested by the Log-Rank test for time-dependent
      outcomes. RESULTS: A total of 57 cases were studied. Median follow-up time was
      387 days. Survival rate was 84,2% at 358 days (SD=6,1%). Thrombectomy primary
      patency rates were 17,9 % at 1 year (SD=6,5%). Limb-salvage rates were 56,6% at 1
      month (SD=6,9%) and 40,3% at 4,5 years (SD=7,1%). Re-intervention rates were
      52,2% at 4,5 years and among those who were reoperated on, limb-salvage rates
      were 71,4% at 12 days (SD=9,9%). To assess the differences according to the type
      of graft operated on, cases were placed into two groups: one group included those
      thrombectomies performed by occlusion of any bypass for aorto-iliac
      revascularization (aortobifemoral, femoro-femoral, femoro-popliteal crossover,
      axilo-unifemoral and axilo-bifemoral) and the other group included all the others
      (for infra-inguinal revascularization). The first group exhibited lower survival
      rates (85,1% vs 96,3% at 11 days, SD<10%, p=0.024). On the other hand, this group
      presented higher patency rates comparing to infra-inguinal revascularization
      group (58,5% vs 81,3% %, SD<10%, p=0,006). Regarding limb-salvage and re
      intervention rates, there were no significant differences between these two
      groups. Interval time between bypass surgery and thrombectomy for its occlusion
      had no impact on patency, neither the additional measures used along with
      thrombectomy for revascularization after occlusion. CONCLUSION: RESULTS of
      surgical thrombectomies after graft thrombosis are discouraging. Other techniques
      such as thrombolysis must be kept in mind in order to achieve better outcomes. In
      some patients one must decide wether to proceed with an attempt to salvage the
      initial procedure or to amputation, which may speed the patient toward the best
      possible outcome.

PMID- 24730019
TI  - Endovascular management of splenic artery aneurysms.
AB  - Visceral aneurysms are rare clinical entities, being the most common in this
      group of pathology the aneurysms of the splenic artery. Its prevalence is
      estimated between 0.2 and 9.7%, according to different authors, however the
      introduction of imaging techniques to assess abdominal pathology have increased
      the incidental findings of these cases. Once diagnosed, treatment should be
      considered, when they are larger than 2 cm. in size. Conventional surgery in most
      cases, together with splenectomy and aneurysm resection is often required.
      Endovascular procedures emerge as a less aggressive and effective treatment
      option. Our institutional experience is presented in the treatment of 13 cases of
      splenic aneurysms, analyzing the profile of the patients, treatments performed
      and results obtained. This type of therapy and the current literature are also
      analysed. 

PMID- 24730020
TI  - [Endovascular management of a thoracoabdominal aortic aneurysm in a chronic
      contained rupture using the "Sandwich technique"].
AB  - OBJECTIVE: The authors report the prompt diagnosis and endovascular treatment
      with the "Sandwich" technique of a chronic contained rupture of a
      thoracoabdominal aortic aneurysm in an unfit patient for open surgery. METHODS: A
      57-year-old male patient with severe pulmonar and cardiac comorbilities presented
      at the emergency department with a contained rupture of a type V thoracoabdominal
      aneurysm, involving the celiac axis. A "Sandwich" technique was performed
      deploying a ViaBahn graft through a transbrachial access interlayed by two Gore
      TAG endoprothesis. RESULTS: At the term of the 1st month of follow-up, no
      endoleaks were observed. DISCUSSION: An impending ruptured thoracoabdominal
      aortic aneurysm was successfully excluded using the "Sandwich" technique, in a
      patient unfit for the conventional open correction.

PMID- 24730021
TI  - Two independent critical pathologies in the same picture.

PMID- 24730022
TI  - The effect of oxidative stress on the bursopentin peptide structure: a
      theoretical study.
AB  - Bursopentin (BP(5), H-Cys(1)-Lys(2)-Arg(3)-Val(4)-Tyr(5)-OH), found in the bursa
      Fabricius of the chicken, is a pentapeptide that protects the organism from
      oxidative stress by reducing the intracellular generation of reactive oxygen
      species. Hydrogen abstraction, a common oxidative reaction occurring in proteins,
      often results in the formation of d amino acid residues. To study the effect of
      this phenomenon on the structure of bursopentin, each of its residues were
      converted from the l configuration to the d configuration, and the structures of
      these peptide epimers were compared to that of the wild-type bursopentin. The
      conformations, secondary structures, compactness and hydrogen bonding of
      bursopentin were compared to its epimers using molecular dynamics simulations and
      first principles quantum chemical computations. It was discovered that the
      repulsion between the side chains of Lys(2) and Arg(3) influenced the
      conformation of the peptide regardless of the configuration of these residues.
      Epimerisation of the Val(4) and Tyr(5) caused a reduction in the compactness of
      bursopentin. In all cases, the occurrence of a turn structure was relatively
      high, especially when Arg(3) was in the d configuration. Thermodynamic analysis
      of the epimerisation process showed that the formation of d amino acid residues
      is favourable. 

PMID- 24730023
TI  - Enhanced photovoltaic performance utilizing effective charge transfers and light
      scattering effects by the combination of mesoporous, hollow 3D-ZnO along with 1D
      ZnO in CdS quantum dot sensitized solar cells.
AB  - A combination of 3-dimensional (3D) hollow mesoporous ZnO microspheres (ZnO HMSP)
      and vertically grown one-dimensional ZnO nanowires (1D ZnO NWs) on a fluorine
      doped tin oxide (FTO) coated glass substrate has been investigated as a
      photoanode for a CdS quantum dot-sensitized solar cell (QSSC). A comparative
      study of the photovoltaic performance of the solar cell with devices fabricated
      with pristine ZnO HMSPs and ZnO NWs was carried out. The proposed photovoltaic
      device exhibits an enhancement in power conversion efficiency (PCE) upto ~74% and
      ~35%, as compared to the 1D ZnO NW and ZnO HMSP based solar cells. The maximum
      incident photon-to-current conversion efficiency (IPCE) for the solar cell was
      observed to be ~40%, whereas for the devices fabricated with bare ZnO HMSP and
      ZnO NW the IPCE were only ~32% and ~19%, respectively. The enhanced photovoltaic
      performance of the solar cell is attributed to the high Brunauer-Emmett-Teller
      (BET) surface area, efficient light-scattering effects and facilitated diffusion
      of the electrolyte for better functioning of the redox couple (S(2-)/Sn(2-)) in
      the hybrid photoanode. Moreover, a faster electron transport through 1D ZnO NWs
      provides better charge collection from the photoactive layer, which leads to an
      increase in the short circuit current density of the device. The present study
      highlights the design and development of a new hybrid photoanode for solar
      harvesting. 

PMID- 24730024
TI  - Luminescent hybrid materials based on covalent attachment of Eu(III)
      tris(bipyridinedicarboxylate) in the mesoporous silica host MCM-41.
AB  - A luminescent inorganic-organic hybrid material was synthesized by covalent
      immobilization of a europium bipyridine carboxylate complex on the inner pore
      walls of the mesoporous silica host MCM-41 using the grafting method. Guest-host
      binding was achieved through double functionalization of the host surface with
      organosilane reagents (trimethylsilyl, TMS, and aminopropyltriethoxysilane,
      APTES) followed by reaction of the active amino sites of the APTES residue with
      the ligand 2,2'-bipyridyl-6,6'-dicarboxylic acid. Addition of EuCl3 solution
      dissolved in ethanol results in the formation of an immobilized complex having
      the probable formula Eu(L)x(3 >= x >= 1)(H2O)y, whose detailed photophysical
      properties were investigated. In the final step, an additional 2,2'-bipyridine-6
      monocarboxylic acid ligand was added in an attempt to complete the coordination
      sphere of the rare earth ion. Each of the synthesis steps was monitored by (1)H,
      (13)C, and (29)Si solid state NMR spectroscopies, allowing for a quantitative
      assessment of the progress of the reaction and the influence of the paramagnetic
      species on the spectra. Based on these data and additional characterizations by
      chemical analysis, thermogravimetric analysis (TGA), N2 sorption, X-ray
      diffraction and FT-IR spectroscopy, a comprehensive quantitative picture of the
      covalent binding and complexation process was developed. 

PMID- 24730025
TI  - One-pot synthesis of Ag/r-GO/TiO2 nanocomposites with high solar absorption and
      enhanced anti-recombination in photocatalytic applications.
AB  - In this paper, we reported a simple one-pot solvothermal approach to fabricate
      Ag/reduced graphene oxide (r-GO)/TiO2 composite photocatalyst under atmospheric
      pressure. Based on the experimental data, we concluded that the introduction of
      Ag into classical graphene-TiO2 system (i) efficiently enlarges the absorption
      range, (ii) improves photogenerated electron separation and (iii) increases
      photocatalysis reaction sites. The optimized sample exhibits prominent
      photocatalysis ability as compared to pure TiO2 under simulated sunlight. We
      further proposed that besides the above three advantages of Ag, a different size
      of Ag nanoparticles is also responsible for the improved photocatalysis ability,
      where small size Ag nanoparticles (2-5 nm) could store a photoexcited electron
      that was generated from TiO2, while large-size Ag nanoparticles could utilize
      visible light due to their localized surface plasmon resonance (LSPR) absorption.
      Our present work gives new insights into the photocatalysis mechanism of noble
      metal/r-GO/TiO2 composites and provides a new pathway into the design of TiO2
      based photocatalysts and promote their practical application in various
      environmental and energy issues. 

PMID- 24730026
TI  - Metal-organic framework derived Fe2O3@NiCo2O4 porous nanocages as anode materials
      for Li-ion batteries.
AB  - Metal-organic frameworks (MOFs) with high surface areas and uniform microporous
      structures have shown potential application in many fields. Here we report a
      facial strategy to synthesize Fe2O3@NiCo2O4 porous nanocages by annealing core
      shell Co3[Fe(CN)6]2@Ni3[Co(CN)6]2 nanocubes in air. The obtained samples have
      been systematically characterized by XRD, SEM, TEM and N2 adsorption-desorption
      analysis. The results show that the Fe2O3@NiCo2O4 porous nanocages have an
      average diameter of 213 nm and a shell thickness of about 30 nm. As anode
      materials for Li-ion batteries, the Fe2O3@NiCo2O4 porous nanocages exhibit a high
      initial discharge capacity of 1311.4 mA h g(-1) at a current density of 100 mA g(
      1) (about 0.1 C). The capacity is retained at 1079.6 mA h g(-1) after 100 cycles.
      The synergistic effect of the different components and the porous hollow
      structure contributes to the outstanding performance of the composite electrode. 

PMID- 24730027
TI  - Molecular imaging and its applications: visualization beyond imagination.

PMID- 24730028
TI  - A Swiss cardiologist rises to the challenge  in the land of the rising sun.

PMID- 24730029
TI  - Echocardiographic assessment of the right  ventricle.

PMID- 24730030
TI  - Controversies in acute cardiovascular care.

PMID- 24730031
TI  - Special issue in honor of W. Owen Saxton, David J. Smith and Dirk Van Dyck on the
      occasion of their 65th birthdays.

PMID- 24730032
TI  - Proceedings of the 2012 Sino-European Symposium on Environment and Health (SESEH
      2012), August 20-25, 2012, Galgay, Ireland.

PMID- 24730033
TI  - Involvement of Nax sodium channel in peripheral nerve regeneration via lactate
      signaling.
AB  - Na(x), a sodium concentration-sensitive sodium channel, is expressed in non
      myelinating Schwann cells of the adult peripheral nervous system, but the
      pathophysiological role remains unclear. We found that functional recovery of the
      hind paw responses from the sciatic nerve transection was delayed in Na(x)
      knockout (Na(x)-/-) mice. Histological analyses showed a decrease in the number
      of regenerated myelinated axons in (Na(x)-/-) sciatic nerves. The delay in the
      recovery in Na(x)-/- mice was improved by lactate and inhibited by a
      monocarboxylate transporter inhibitor. In vitro experiments using cultured
      Schwann cells showed that lactate release was enhanced by endothelin (ET)-1 and
      blocked by an ET receptor type B antagonist. Here, it is conceivable that Na(x)
      was activated by ET-1. The amount of lactate release by ET-1 was lower in Na(x)-/
      mice than in wild-type mice. These results indicated that Na(x) is functionally
      coupled to ET for lactate release via ET receptor type B and is involved in
      peripheral nerve regeneration.

PMID- 24730034
TI  - Health information technology adoption in New Zealand optometric practices.
AB  - BACKGROUND: Health information technology (HIT) has the potential to
      fundamentally change the practice of optometry and the relationship between
      optometrists and patients and to improve clinical outcomes. This paper aims to
      provide data on how health information technology is currently being used in New
      Zealand optometric practices. Also this paper aims to explore the potential
      benefits and barriers to the future adoption of health information technology in
      New Zealand. METHODS: One hundred and six New Zealand optometrists were surveyed
      about their current use of health information technology and about potential
      benefits and barriers. In addition, 12 semi-structured interviews were carried
      out with leaders of health information technology in New Zealand optometry. The
      areas of interest were the current and intended use of HIT, the potential
      benefits of and barriers to using HIT in optometric offices and the level of
      investment in health information technology. RESULTS: Nearly all optometrists
      (98.7 per cent) in New Zealand use computers in their practices and 93.4 per cent
      of them use a computer in their consulting room. The most commonly used clinical
      assessment technology in optometric practices in New Zealand was automated
      perimeter (97.1 per cent), followed by a digital fundus/retinal camera (82.6 per
      cent) and automated lensometer (62.9 per cent). The pachymeter is the technology
      that most respondents intended to purchase in the next one to five years (42.6
      per cent), followed by a scanning laser ophthalmoscope (36.8 per cent) and
      corneal topographer (32.9 per cent). The main benefits of using health
      information technology in optometric practices were improving patient perceptions
      of 'state of the art' practice and providing patients with information and
      digital images to explain the results of assessment. Barriers to the adoption of
      HIT included the need for frequent technology upgrades, cost, lack of time for
      implementation, and training. CONCLUSIONS: New Zealand optometrists are using HIT
      broadly in their practices and expect HIT use to increase over time.

PMID- 24730035
TI  - Reliability of the ERN across multiple tasks as a function of increasing errors.
AB  - Event-related potential (ERP) studies of error-processing have characterized the
      error-related negativity (ERN) as a negative deflection occurring after the
      commission of an error at frontocentral sites. The ERN has frequently been
      examined in the context of individual differences and has been proposed as a
      neurobehavioral risk marker. Given this, it is important to characterize the
      psychometric properties of the ERN across multiple tasks as a function of
      increasing trial numbers in order to establish task-specific psychometric
      properties for efficient assessments in clinical or applied settings. The current
      study examines the internal reliability of the ERN across the flankers, Stroop,
      and go/no-go tasks as a function of error number. Results suggest that although
      the tasks all elicit the ERN reliably, important psychometric differences emerged
      indicating that the flankers task might be prioritized when assessing the ERN.

PMID- 24730036
TI  - Similarity in temporal variation in sex-biased dispersal over short and long
      distances in the dark-eyed junco, Junco hyemalis.
AB  - Patterns of sex-biased dispersal (SBD) are typically consistent within taxa, for
      example female-biased in birds and male-biased in mammals, leading to theories
      about the evolutionary pressures that lead to SBD. However, generalizations about
      the evolution of sex biases tend to overlook that dispersal is mediated by
      ecological factors that vary over time. We examined potential temporal variation
      in between- and within-population dispersal over an 11-year period in a bird, the
      dark-eyed junco (Junco hyemalis). We measured between-population dispersal
      patterns using genetic assignment indices and found yearly variation in which sex
      was more likely to have immigrated. When we measured within-population spatial
      genetic structure and mark-recapture dispersal distances, we typically found
      yearly SBD patterns that mirrored between-population dispersal, indicating common
      eco-evolutionary causes despite expected differences due to the scale of
      dispersal. However, in years without detectable between-population sex biases, we
      found genetic similarity between nearby males within our population. This
      suggests that, in certain circumstances, ecological pressures may act on within
      population dispersal without affecting dispersal between populations.
      Alternatively, current analytical tools may be better able to detect within
      population SBD. Future work will investigate potential causes of the observed
      temporal variation in dispersal patterns and whether they have greater effects on
      within-population dispersal.

PMID- 24730037
TI  - Parallel and nonparallel genome-wide divergence among replicate population pairs
      of freshwater and anadromous Atlantic salmon.
AB  - Little is known about the genetic basis differentiating resident and anadromous
      forms found in many salmonid species. Using a medium-density SNP array, we
      documented genomic diversity and divergence at 2336 genetically mapped loci among
      three pairs of North American anadromous and freshwater Atlantic salmon
      populations. Our results show that across the genome, freshwater populations have
      lower diversity and a smaller proportion of private polymorphism relative to
      anadromous populations. Moreover, differentiation was more pronounced among
      freshwater than among anadromous populations at multiple spatial scales,
      suggesting a large effect of genetic drift in these isolated freshwater
      populations. Using nonhierarchical and hierarchical genome scans, we identified
      hundreds of markers spread across the genome that are potentially under divergent
      selection between anadromous and freshwater populations, but few outlier loci
      were repeatedly found in all three freshwater-anadromous comparisons. Similarly,
      a sliding window analysis revealed numerous regions of high divergence that were
      nonparallel among the three comparisons. These last results show little evidence
      for the parallel evolution of alleles selected for in freshwater populations, but
      suggest nonparallel adaptive divergence at many loci of small effects distributed
      through the genome. Overall, this study emphasizes the important role of genetic
      drift in driving genome-wide reduction in diversity and divergence in freshwater
      Atlantic salmon populations and suggests a complex multigenic basis of adaptation
      to resident and anadromous strategies with little parallelism.

PMID- 24730038
TI  - Proceedings of the 14th Servier-IGIS Symposium, 21-24 March 2013, St Jean Cap
      Ferrat, France.

PMID- 24730039
TI  - Proceedings of the WHO Progress Review Workshop for the Public Health Research
      Agenda for Influenza, 14-15 November, 2011, Geneva, Switzerland.

PMID- 24730040
TI  - Low plant density enhances gene dispersal in the Amazonian understory herb
      Heliconia acuminata.
AB  - In theory, conservation genetics predicts that forest fragmentation will reduce
      gene dispersal, but in practice, genetic and ecological processes are also
      dependent on other population characteristics. We used Bayesian genetic analyses
      to characterize parentage and propagule dispersal in Heliconia acuminata L. C.
      Richard (Heliconiaceae), a common Amazonian understory plant that is pollinated
      and dispersed by birds. We studied these processes in two continuous forest sites
      and three 1-ha fragments in Brazil's Biological Dynamics of Forest Fragments
      Project. These sites showed variation in the density of H. acuminata. Ten
      microsatellite markers were used to genotype flowering adults and seedling
      recruits and to quantify realized pollen and seed dispersal distances,
      immigration of propagules from outside populations, and reproductive dominance
      among parents. We tested whether gene dispersal is more dependent on
      fragmentation or density of reproductive plants. Low plant densities were
      associated with elevated immigration rates and greater propagule dispersal
      distances. Reproductive dominance among inside-plot parents was higher for low
      density than for high-density populations. Elevated local flower and fruit
      availability is probably leading to spatially more proximal bird foraging and
      propagule dispersal in areas with high density of reproductive plants.
      Nevertheless, genetic diversity, inbreeding coefficients and fine-scale spatial
      genetic structure were similar across populations, despite differences in gene
      dispersal. This result may indicate that the opposing processes of longer
      dispersal events in low-density populations vs. higher diversity of contributing
      parents in high-density populations balance the resulting genetic outcomes and
      prevent genetic erosion in small populations and fragments.

PMID- 24730041
TI  - Proceedings of the ICRM-LLRMT'12: 6th International Conference on Radionuclide
      Metrology-Low Level Radioactivity Measurement Techniques, September 17-21, 2012,
      Korea.

PMID- 24730042
TI  - [Michel Bonduelle, 1912-2013].

PMID- 24730043
TI  - [Neuroleptic metabolic dysfunctions in patients treated with new generation
      antipsychotics].

PMID- 24730044
TI  - [The effect of the instability of cervical spine on the hemodynamics in the
      vertebrobasilar system].
AB  - 256 patients with cephalgia were examined. The main cephalgia cause was a
      cervical instability. We showed importance of extended examinations for cephalgia
      pathogenesis. We estimated cerebral circulation by ultrasound (cerebral blood
      flow registration) methods. We found an intact blood flow in both vascular
      systems (arterial and venous) in 19.9% cases. Cervical instability more 3 mm
      vertebra dislocation was not always a cause of vertebral discirculation. Quite
      often a vertebra dislocation under 3 mm was a result of vertebra-basilar
      disordes.

PMID- 24730045
TI  - [The dysfunctional neurologic disorder - chronic pelvic pain].

PMID- 24730046
TI  - [Treatment of back pain (ketoprofen and other methods)].

PMID- 24730047
TI  - What are the harms of refusing to allow living kidney donation? An expanded view
      of risks and benefits.
AB  - Recent Organ Procurement and Transplantation Network policies relating to living
      kidney donation (LKD)warrant renewed attention to the ethics of transplantation
      from living donors. These policies focus on risks related to potential donor
      evaluation, informed consent and follow-up. The ethical basis of living donation
      is a favorable risk/benefit ratio for the donor, but regulations and research
      have given less attention to the benefits of donation. Relatedly, the transplant
      field has also failed to consider potential harms from denying patients the
      opportunity to donate. These harms may be substantial in the setting of directed
      kidney donation to a spouse/partner, sibling or child.We argue that complete
      assessment of donor risks and benefits demands consideration of not only the
      risks and benefits of donation, but also those of refusing a donor. In contrast
      to the ever-expanding literature on risks of donation, there are no data
      describing outcomes for individuals who were turned down as kidney donors. We
      consider factors contributing to this omission in the transplant literature,
      argue that current regulations may perpetuate a narrow understanding of relevant
      risks and benefits in LKD, and identify areas for improvement in research and
      clinical practice.

PMID- 24730048
TI  - Spi6 protects alloreactive CD4(+) but not CD8 (+) memory T cell from granzyme B
      attack by double-negative T regulatory cell.
AB  - Memory T (Tm) cells pose a major barrier to long-term transplant survival.
      Whether regulatory T cells (Tregs)can control them remains poorly defined.
      Previously,we established that double-negative (DN) Tregs suppress effector T
      (Teff) cells. Here, we demonstrate that DNTregs effectively suppress
      CD4+/CD8+Teff and CD8+Tm but not CD4+Tm cells, whereas the suppression on CD8+Tm
      is abrogated by perforin (PFN) deficiency in DNTregs. Consistently, in a BALB/c
      to B6-Rag1-/-skin transplantation, transfer of DN Tregs suppressed the rejection
      mediated by CD4p/CD8+Teff and CD8+Tmcells (76.0+/-4.9, 87.5+/-5.0 and 63.0+/-4.7
      days, respectively)but not CD4pTmcells (25.3+/-1.4 days). Both CD8p effector
      memory T and central memory T compartments significantly reduced after DN Treg
      transfer. CD4+Tm highly expresses granzyme B (GzmB) inhibitor serine protease
      inhibitor-6 (Spi6). Spi6 deficiency renders CD4pTm susceptible to DN Treg
      suppression. In addition,transfer of WT DN Tregs, but not PFN-/-DN
      Tregs,inhibited the skin allograft rejection mediated by Spi6-/-CD4pTm(75.5+/-7.9
      days). In conclusion, CD4+ and CD8+Tm cells differentially respond toDNTregs'
      suppression.The GzmB resistance conferred by Spi6 in CD4pTm cells might hint at
      the physiological significance of Tmpersistence

PMID- 24730049
TI  - High CTLA-4 expression on Th17 cells results in increased sensitivity to CTLA-4
      coinhibition and resistance to belatacept.
AB  - The CD28/cytotoxic T-lymphocyte antigen 4 (CTLA-4)blocker belatacept selectively
      inhibits alloreactive T cell responses but is associated with a high incidence of
      acute rejection following renal transplantation,which led us to investigate the
      etiology of belatacept-resistant graft rejection. T cells can differentiate into
      functionally distinct subsets of memory T cellsthat collectively enable
      protection against diverse classes of pathogens and can cross-react with
      allogeneicantigen and mediate graft rejection. T helper 17(Th17) cells are a pro
      inflammatory CD4+ lineage that provides immunity to pathogens and are pathogenic
      in autoimmune disease. We found that T helper 1 (Th1)and Th17 memory compartments
      contained a similar frequency of divided cells following allogeneic
      stimulation.Compared to Th1 cells, Th17 memory cells expressed significantly
      higher levels of the coinhibitory molecule CTLA-4. Stimulation in the presence of
      belatacept inhibited Th1 responses but augmented Th17 cells due to greater
      sensitivity to coinhibition by CTLA-4. Th17 cells from renal transplant
      recipients were resistant to ex vivo CD28/CTLA-4 blockade with belatacept, and an
      elevated frequency of Th17 memory cells was associated with acute rejection
      during belatacept therapy. These data highlight important differences in
      costimulatory and coinhibitory requirements of CD4+ memory subsets, and
      demonstrate that the heterogeneity of pathogen-derived memory has implications
      for immunomodulation strategies.

PMID- 24730050
TI  - A randomized trial of the effects of nebulized albuterol on pulmonary edema in
      brain-dead organ donors.
AB  - Donor lung utilization rates are persistently low primarily due to donor lung
      dysfunction. We hypothesized that a treatment that enhances the resolution of
      pulmonary edema by stimulating the rate of alveolar fluid clearance would improve
      donor oxygenation and increase donor lung utilization. We conducted a randomized,
      blinded, placebo-controlled trial of aerosolized albuterol (5mg q4h) versus
      saline placebo during active donor management in 506 organ donors.The primary
      outcome was change in oxygenation arterial partial pressure of oxygen/fraction of
      inspired oxygen [PaO2/FiO2] from enrollment to organ procurement.The albuterol
      (n1/4260) and placebo (n1/4246)groups were well matched for age, gender,
      ethnicity,smoking, and cause of brain death. The change in PaO2/FiO2 from
      enrollment to organ procurement did not differ between treatment groups
      (p1/40.54) nor did donor lung utilization (albuterol 29% vs. placebo
      32%,p1/40.44). Donors in the albuterol versus placebo groups were more likely to
      have the study drug dose reduced (13% vs. 1%, p<0.001) or stopped (8% vs.
      0%,p<0.001) for tachycardia. In summary, treatment with high dose inhaled
      albuterol during the donor management period did not improve donor oxygenation or
      increase donor lung utilization but did cause tachycardia.High dose aerosolized
      albuterol should not be used in donors to enhance the resolution of pulmonary
      edema.

PMID- 24730051
TI  - Pain identifies squamous cell carcinoma in organ transplant recipients: the SCOPE
      ITSCC PAIN study.
AB  - Organ transplant recipients (OTR) are at high risk for cutaneous squamous cell
      carcinomas (SCC). We aimed to define clinically meaningful patient-reported
      warning signals predicting the presence of invasive SCC.Patient-reported signs
      and symptoms of 812 consecutively biopsied skin lesions from 410 OTR were
      determined by questionnaire and physical examination and related to the
      subsequent biopsy-proven diagnoses. Receiver-operating characteristic (ROC) curve
      analyses were used as a measure of distinction between the predictive values of
      patient-reported warning signals and the occurrence of SCC. Pain was an
      independent predictive patient-reported warning signal for a biopsy-proven
      invasive SCC. The odds ratio from the fully adjusted model predicting SCC was
      4.4(95% confidence interval: 2.4-8.2). Higher scores on the visual analog scale
      (VAS) for pain were associated witha greater likelihood for the presence of SCC
      compared to none or mild pain. The for scores on the VAS from 1to 3, 4 to 6 and 7
      to 10 were 4.9 (2.2-10.5), 2.3 (0.96-5.5)and 16.5 (3.6-75.8), respectively. Pain
      is the most powerful patient-reported warning signal for invasive cutaneous SCC
      in OTR. Empowerment of patients by education could accelerate diagnosis and
      treatment of cutaneous SCC.

PMID- 24730052
TI  - Utility of the multiple-stimulus without replacement procedure and stability of
      preferences of older adults with dementia.
AB  - Paired-stimulus preference assessments have been used effectively with
      individuals with dementia to identify stimuli to increase engagement and to
      minimize negative affect and problem behavior.We evaluated whether a multiple
      stimulus without replacement preference assessment could be used with older
      adults with dementia and whether preferences remained stable over time. Seven
      participants completed preference assessments and confirmatory engagement
      analyses every few weeks for 3 to 5 months; 1 participant failed to complete any
      preference assessments. Five of the 7 remaining participants displayed higher
      levels of engagement with the highest ranked stimuli than with the lowest ranked
      stimuli, confirming the hierarchy in the preference assessment. For the other 2
      participants, lowest ranked items resulted in higher levels of engagement than
      the highest ranked items. Four participants exhibited stable patterns of
      preference over 3 to 5 months with correlation coefficients exceeding r1/4.5,
      suggesting that preferences may remain stable for some individuals with dementia.

PMID- 24730053
TI  - Eczema phenotypes are associated with multiple vitamin D pathway genes in Chinese
      children.
AB  - BACKGROUND: Vitamin D is increasingly recognized to play crucial roles in
      cutaneous immunity, and vitamin D treatment improved eczema control in small
      clinical trials. Several vitamin D-related genes were associated with asthma, but
      there are no data for eczema. METHODS: Twenty-three single-nucleotide
      polymorphisms (SNPs) of five vitamin D-related genes (CYP27A1, CYP2R1, CYP27B1,
      GC and VDR) were genotyped in 1442 Chinese children with eczema and 1231 non
      allergic controls. SNPs that followed Hardy-Weinberg equilibrium and yielded >=
      95% genotyping call-rate were included. Haplotypic associations and SNP-SNP
      interactions for eczema diagnosis and subphenotypes were analysed. RESULTS:
      Atopic eczema was associated with rs4674343 of CYP27A1 (odds ratio 0.66, 95%
      confidence interval 0.53-0.83, P = 0.0004). Increased eosinophil percentage was
      associated with CYP2R1 rs2060793A (P = 0.001) and rs1933064A (P = 0.001). Two
      CYP2R1 haplotypes increased eczema risk whereas one VDR haplotype lowered eczema
      risk. GC rs7041 and CYP2R1 rs7935792 interacted to modulate total IgE (cross
      validation consistency 10/10, P = 0.047). Specifically, high-risk eczema patients
      had higher log-transformed total IgE than low-risk patients (2.76 +/- 0.76 vs
      2.60 +/- 0.80, P = 0.002). CONCLUSION: A vitamin D-related SNP rs4674343 on
      CYP27A1 was found to be protective against atopic eczema. CYP2R1 and VDR
      haplotypes altered eczema susceptibility and eosinophil percentage, and GC and
      CYP2R1 interacted to determine total IgE among eczema patients.

PMID- 24730054
TI  - Reply: To PMID 23401475.

PMID- 24730056
TI  - Bioinspired, cysteamine-catalyzed co-silicification of (1H, 1H, 2H,
      2HPerfluorooctyl) triethoxysilane and tetraethyl orthosilicate: formation of
      superhydrophobic surfaces.
AB  - Bioinspired silicification attracts a great deal of interest because of its
      physiologically relevant, mild conditions for hydrolysis and condensation of
      silica precursors, which makes the bioinspired approach superior to the
      conventional sol-gel process, particularly when dealing with biological entities.
      However, the morphological control of silica structures with incorporation of
      functional groups in the bioinspired silicilication has been unexplored. In this
      work, we co-silicificated (1H, 1H, 2H, 2H-perfluorooctyl)triethoxysilane and
      tetraethyl orthosilicate to investigate the morphological evolution of
      fluorinated silica structures in the cetyltrimethylammonium bromide-mediated,
      cysteamine-catalyzed silicification. The generated micrometer-long wormlike and
      spherical silica structures display superhydrophobicity after film formation.
      Interestingly, the measurement of dynamic water contact angles shows that the
      morphological difference leads to a different wetting state, either the self
      cleaning or the pinning state of the superhydrophobic surface.

PMID- 24730055
TI  - Chronic desipramine treatment rescues depression-related, social and cognitive
      deficits in Engrailed-2 knockout mice.
AB  - Engrailed-2 (En2) is a homeobox transcription factor that regulates
      neurodevelopmental processes including neuronal connectivity and elaboration of
      monoaminergic neurons in the ventral hindbrain. We previously reported
      abnormalities in brain noradrenergic concentrations in En2 null mutant mice that
      were accompanied by increased immobility in the forced swim test, relevant to
      depression. An EN2 genetic polymorphism has been associated with autism spectrum
      disorders, and mice with a deletion in En2 display social abnormalities and
      cognitive deficits that may be relevant to multiple neuropsychiatric conditions.
      This study evaluated the ability of chronic treatment with desipramine (DMI), a
      selective norepinephrine (NE) reuptake inhibitor and classical antidepressant, to
      reverse behavioral abnormalities in En2-/- mice. Desipramine treatment
      significantly reduced immobility in the tail suspension and forced swim tests,
      restored sociability in the three-chambered social approach task and reversed
      impairments in contextual fear conditioning in En2-/- mice. Our findings indicate
      that modulation of brain noradrenergic systems rescues the depression-related
      phenotype in En2-/- mice and suggest new roles for NE in the pathophysiology of
      the social and cognitive deficits seen in neuropsychiatric disorders such as
      autism or schizophrenia.

PMID- 24730057
TI  - Energy transfer in aminonaphthalimide-boron-dipyrromethene (BODIPY) dyads upon
      one- and two-photon excitation: applications for cellular imaging.
AB  - Aminonaphthalimide-BODIPY energy transfer cassettes were found to show very fast
      (kEET ~ 10(10)-10(11) s(-1) and efficient BODIPY fluorescence sensitization. This
      was observed upon one- and two-photon excitation, which extends the application
      range of the investigated bichromophoric dyads in terms of accessible excitation
      wavelengths. In comparison with the direct excitation of the BODIPY chromophore,
      the two-photon absorption cross-section delta of the dyads is significantly
      incremented by the presence of the aminonaphthalimide donor [delta ~ 10 GM for
      the BODIPY versus 19-26 GM in the dyad at lambda(exc)=840 nm; 1 GM (Goeppert
      Mayer unit)=10(-50) cm(4) smolecule(-1) photon-(1)]. The electronic decoupling of
      the donor and acceptor, which is a precondition for the energy transfercassette
      concept, was demonstrated by time-dependent density functional theory
      calculations. The applicability of the new probes in the one- and twophoton
      excitation mode was demonstrated in a proof-of-principle approach in the
      fluorescence imaging of HeLa cells. To the best of our knowledge, this is the
      first demonstration of the merging of multiphoton excitation with the energy
      transfer cassette concept for a BODIPY-containing dyad.

PMID- 24730058
TI  - Retraction: Correlation of electrocardiographic changes and myocardial fibrosis
      inpatients with hypertrophic cardiomyopathy detected by cardiac magnetic
      resonance imaging.

PMID- 24730059
TI  - Lipid bilayer arrays: cyclically formed and measured.
AB  - Artificial lipid bilayers have many uses. They are well established for
      scientific studies of reconstituted ion channels, used to host engineered pore
      proteins for sensing, and can potentially be applied in DNA sequencing. Droplet
      bilayers have significant technological potential for enabling many of these
      applications due to their compatibility with automation and array platforms. To
      further develop this potential, we have simplified the formation and electrical
      measurement of droplet bilayers using an apparatus that only requires fluid
      dispensation. We achieved simultaneous bilayer formation and measurement over a
      32-element array with ~80% yield and no operator input following fluid addition.
      Cycling these arrays resulted in the formation and measurement of 96 out of 120
      possible bilayers in 80 minutes, a sustainable rate that could significantly
      increase with automation and greater parallelization. This turn-key, high-yield
      approach to making artificial lipid bilayers requires no training, making the
      capability of creating and measuring lipid bilayers and ion channels accessible
      to a much wider audience. In addition, this approach is low-cost, parallelizable,
      and automatable, allowing high-throughput studies of ion channels and pore
      proteins in lipid bilayers for sensing or screening applications.

PMID- 24730060
TI  - Long-term consequences of perinatal fatty acid amino hydrolase inhibition.
AB  - BACKGROUND AND PURPOSE: Fatty acid amide hydrolase inhibitors show promise as a
      treatment for anxiety, depression and pain. Here we investigated whether
      perinatal exposure to URB597, a fatty acid amide hydrolase inhibitor, alters
      brain development and affects behaviour in adult mice. EXPERIMENTAL APPROACH:
      Mouse dams were treated daily from gestational day 10.5 to 16.5 with 1, 3 or 10
      mg kg-1 URB597. MS was used to measure a panel of endocannabinoids and related
      lipid compounds and brain development was assessed at embryonic day 16.5.
      Separate cohorts of mouse dams were treated with 10 mg kg-1 URB597, from
      gestational day 10.5 to postnatal day 7, and the adult offspring were assessed
      with a battery of behavioural tests. KEY RESULTS: Perinatal URB597 exposure
      elevated anandamide and related N-acyl amides. URB597 did not induce signs of
      toxicity or affect dam weight gain, neurogenesis or axonal development at
      embryonic day 16.5. It did lead to subtle behavioural deficits in adult
      offspring, manifested by reduced cocaine-conditioned preference, increased
      depressive behaviours and impaired working memory. Anxiety levels, motor function
      and sensory-motor gating were not significantly altered. CONCLUSIONS AND
      IMPLICATIONS: Taken together, the present results highlight how exposure to
      elevated levels of anandamide and related N-acyl amides during brain development
      can lead to subtle alterations in behaviour in adulthood. LINKED ARTICLES: This
      article is part of a themed section on Cannabinoids 2013. To view the other
      articles in this section visit http://dx.doi.org/10.1111/bph.2014.171.issue-6

PMID- 24730061
TI  - Antiplatelet activity of nifedipine is mediated by inhibition of NF-kappaB
      activation caused by enhancement of PPAR-beta/-gamma activity.
AB  - BACKGROUND AND PURPOSE: The transcription factor NF-kappaB, stimulates platelet
      aggregation through a non-genomic mechanism. Nifedipine, a voltage-gated L-type
      calcium channel blocker, is widely used to treat hypertension. Nifedipine also
      displays antiplatelet activity, but the underlying mechanisms involved remain
      unclear. This study was designed to investigate whether the antiplatelet effects
      of nifedipine are mediated by regulating NF-kappaB-dependent responses.
      EXPERIMENTAL APPROACH: Platelet aggregation was measured turbidimetrically using
      an aggregometer. NF-kappaB and PPAR activation, intracellular Ca2+ mobilization,
      PKCalpha activity, surface glycoprotein IIb/IIIa (GPIIb/IIIa) expression and
      platelet activation-related signalling pathways were determined in control and
      nifedipine-treated platelets in the presence or absence of PPAR antagonists or
      betulinic acid, a NF-kappaB activator. KEY RESULTS: Exposure of platelets to
      nifedipine significantly increased the PPAR-beta/-gamma activity in activated
      human platelets. Treatment with nifedipine reduced collagen-induced NF-kappaB
      events, including the phosphorylation of IkappaB kinase-beta, IkappaBalpha and
      p65NF-kappaB, which were markedly attenuated by GSK0660, a PPAR-beta antagonist,
      or GW9662, a PPAR-gamma antagonist. Furthermore, the interaction of PPAR-beta/
      gamma with NF-kappaB and the PPAR-beta/-gamma-up-regulated NO/cGMP/PKG1 cascade
      may contribute to inhibition of NF-kappaB activation by nifedipine. Suppressing
      PPAR-beta/-gamma activity or increasing NF-kappaB activation greatly reversed the
      inhibitory effect of nifedipine on collagen-induced platelet aggregation,
      intracellular Ca2+ mobilization, PKCalpha activity and surface GPIIb/IIIa
      expression.CONCLUSIONS AND IMPLICATIONSPPAR-beta/-gamma-dependent inhibition of
      NF-kappaB activation contributes to the antiplatelet activity of nifedipine.
      These findings provide a novel mechanism underlying the beneficial effects of
      nifedipine on platelet hyperactivity-related vascular and inflammatory diseases.

PMID- 24730062
TI  - Long-term suppression of EAE relapses by pharmacological impairment of epitope
      spreading.
AB  - BACKGROUND AND PURPOSE: Immune events sustaining dendritic cell (DC)-dependent
      epitope spreading (ES) are of key relevance to the development of relapses during
      multiple sclerosis (MS). Although no drugs are currently available to target ES,
      its inhibition would represent a major advancement in MS therapy. Inhibitors of
      the enzyme PARP-1 afford protection in animal models of MS, such as experimental
      autoimmune encephalomyelitis (EAE). These drugs epigenetically impair antigen
      presentation by DCs, but whether these drugs affect ES is unknown. Here, we
      investigated whether short-term treatments with these compounds would impair ES,
      thereby preventing EAE relapses. EXPERIMENTAL APPROACH: We used a model of
      relapsing EAE in SJL mice and also adopted in vivo and ex vivo models of DC
      dependent T-cell polarization. The effect of PARP-1 inhibitors on ES was
      evaluated at the humoral and cellular level. KEY RESULTS: Short-term treatments
      with PARP-1 inhibitors during the acute phase of relapsing EAE of mice induced,
      at later times, more tolerogenic DCs, increased numbers of Treg cells and
      impairment of ES at the humoral and cellular level. These effects are followed by
      long-lasting reduction of relapse severity and incidence, although drug treatment
      had been discontinued for several weeks. PARP-1 inhibitors also induced
      tolerogenic DCs and increased Treg cells number and function in a model of
      ovalbumin immunization. CONCLUSIONS AND IMPLICATIONS: Our data emphasize the
      therapeutic potential of PARP-1 inhibitors in the treatment of relapsing
      remitting MS and additional ES-driven autoimmune disorders.

PMID- 24730064
TI  - Meet the 2014 EHR game changers.

PMID- 24730065
TI  - The promise, peril of HIX.

PMID- 24730063
TI  - Towards selective inhibition of histone deacetylase isoforms: what has been
      achieved, where we are and what will be next.
AB  - Histone deacetylases (HDACs) are widely studied targets for the treatment of
      cancer and other diseases. Up to now, over twenty HDAC inhibitors have entered
      clinical studies and two of them have already reached the market, namely the
      hydroxamic acid derivative SAHA (vorinostat, Zolinza) and the cyclic depsipeptide
      FK228 (romidepsin, Istodax) that have been approved for the treatment of
      cutaneous T-cell lymphoma (CTCL). A common aspect of the first HDAC inhibitors is
      the absence of any particular selectivity towards specific isozymes. Some of
      molecules resulted to be "pan"-HDAC inhibitors, while others are class I
      selective. In the meantime, the knowledge of HDAC biology has continuously
      progressed. Key advances in the structural biology of various isozymes, reliable
      molecular homology models as well as suitable biological assays have provided new
      tools for drug discovery activities. This Minireview aims at surveying these
      recent developments as well as the design, synthesis and biological
      characterization of isoform-selective derivatives.

PMID- 24730066
TI  - Cardiovascular exams.  An inside look at your heart and blood vessels.

PMID- 24730067
TI  - Healthy traveling.  Plan ahead for a bon voyage.

PMID- 24730068
TI  - Mindfulness.  Learning to live in the moment.

PMID- 24730069
TI  - Diverticular disease.  Fiber as therapy.

PMID- 24730070
TI  - Health tips.  Taking a breather.

PMID- 24730071
TI  - Storing up brainpower for later years.

PMID- 24730072
TI  - Post-meal walking reduces blood glucose.

PMID- 24730073
TI  - Pericarditis.  Heart inflammation.

PMID- 24730074
TI  - Lowering blood pressure.  Devices that help.

PMID- 24730075
TI  - Acetaminophen.  Generally a better choice.

PMID- 24730076
TI  - My doctor is concerned about my resting heart rate, which is 89.  For now, he
      wants me to try to get in more activity and lose a little extra weight to try to
      lower it.  Why should heart rate be a concern?

PMID- 24730077
TI  - I developed tennis elbow from doing yardwork.  It's better now, but I'm wondering
      how to avoid this in the future.

PMID- 24730078
TI  - Fast algorithm for peptide sequencing by mass spectroscopy.
AB  - An automatic algorithm for sequencing polypeptides from fast atom bombardment
      tandem mass spectra is presented.Based on graph theory considerations it finds
      the most probable sequences, even if the amino acid composition is unknown, by
      scoring mass differences. The algorithm is fast as the computing time increases
      by less than the square of the number of amino acids. Pairs of two or three amino
      acids are proposed to explain the gap if peaks are missing.

PMID- 24730079
TI  - Evaluating and improving cleaning practices in the OR.

PMID- 24730080
TI  - Strategies for making best use of surgical supplies.

PMID- 24730081
TI  - Pediatric robotic surgery program requires multidisciplinary team collaboration.

PMID- 24730082
TI  - Use of digital breast tomosynthesis with mammography for breast cancer screening
      or diagnosis.

PMID- 24730083
TI  - Artificial lumbar disc arthroplasty.

PMID- 24730084
TI  - CYP2D6 pharmacogenomics of tamoxifen treatment.

PMID- 24730085
TI  - Transcranial magnetic stimulation for depression.

PMID- 24730086
TI  - Percutaneous tibial nerve stimulation for the treatment of voiding dysfunction.

PMID- 24730087
TI  - [A new drug for basal cell carcinoma].

PMID- 24730088
TI  - No trust is an island when failing financially.

PMID- 24730089
TI  - The NHS is awash with information but failings continue.

PMID- 24730090
TI  - Use the power of big data.

PMID- 24730092
TI  - Nursing. Be not afraid of greatness.

PMID- 24730091
TI  - Workforce. Teach each other holistic care.

PMID- 24730093
TI  - Accountable care organizations--the promise, perils and pathway to value for plan
      sponsors.
AB  - If the potential of accountable care organizations (ACOs) is realized, they could
      significantly transform how health care is delivered and financed, bringing the
      promise of high-quality affordable health care within reach. This article
      explores the root causes that have handicapped the value in the health care
      delivery system historically and the critical requirements to overcome those
      issues. The authors describe how commercial and Medicare ACOs attempt to address
      those issues, the potential land mines in the transition to a new paradigm and
      the principles plan sponsors should consider in understanding and integrating
      ACOs into their health care benefits strategy.

PMID- 24730094
TI  - Accountable care organizations--an employer POV primer.
AB  - The accountable care organization (ACO) has emerged as the centerpiece of
      postreform initiatives to improve the delivery of quality, cost-efficient care.
      As the primary partners in delivering ACOs, payers and providers have begun to
      collaborate on the opportunities presented by the legislation. For employers,
      however, this new approach to managed health care delivery models will present
      challenges in adoption different from its predecessors: preferred provider
      organizations, health maintenance organizations and consumer-driven models. This
      article identifies these challenges and helps employers understand how they can
      respond in ways that make them active participants in the emergence of ACOs and
      secure the potential value of ACOs for their own organizations. For employers,
      the method to capturing the value of these emerging delivery models is to have a
      broad understanding of the evolving payer and provider marketplace, how to access
      or develop ACOs, and how smart decisions today can improve the future landscape
      of health care.

PMID- 24730095
TI  - The power of data--from data mining to consumer pricing and quality-of-care
      tools.
AB  - Transparency tools, whether offered by carriers or third-party administrators,
      rely on adequate experience, by market and by service, to provide information to
      consumers about health care costs and quality of care. The opportunities for
      savings to individual consumers and to employer-sponsored health plans are
      clearly significant and possible if people will use the tools and act. This
      article reviews two studies showing a shift in consumer claims experience to less
      costly services afte the implementation of a transparency tool and when combined
      with a consumer-driven health plan. It also outlines best practices employers can
      implement to carefully craft interventions to engage and create value in the
      minds of health care consumers.

PMID- 24730096
TI  - Can private health care exchanges improve the U.S. health care system?
AB  - There are already a number of firms entering the active employee exchange
      marketplace, and the trend will continue as more employers show interest in this
      model. Private health exchanges will be a permanent and significant avenue for
      health care benefits delivery because they are dynamic, powerful and necessary
      for employers aiming to achieve lower, predictable health care costs. The
      emergence of efficient and effective health exchanges, combined with a
      responsibility to provide affordable health coverage, presents an opportunity for
      employers to take advantage of new options available to help manage costs and
      improve the health of their population in a way that leads to a workforce that is
      healthy, present and productive.

PMID- 24730097
TI  - Incorporating wellness into employee benefit strategies--why it makes sense.
AB  - By putting together a comprehensive wellness strategy, employers are not only
      "doing the right thing" but also are able to see, believe and maintain the
      tangible return on investment (ROI) that wellness programs are capable of
      delivering. This article discusses employers' ROI from wellness initiatives, as
      well as innovations that support a culture of wellness and what enhanced
      opportunities for increasing employee wellness are available under health care
      reform. It also describes how wellness is a component of population health
      management, as well as a core component of the health care delivery system.

PMID- 24730099
TI  - The new NHS structure is unstable.

PMID- 24730098
TI  - We have a radical plan to build up primary care.

PMID- 24730100
TI  - Flaws of the friends and family test.

PMID- 24730101
TI  - Commissioning. The road to radical change need not be rocky.

PMID- 24730102
TI  - Technology. The e-prescribing future looks bright.

PMID- 24730103
TI  - Ensuring staff are safe and sound.

PMID- 24730104
TI  - Tort reform. While some states have taken action to cap damages, fear of
      litigation still drives defensive medicine.

PMID- 24730105
TI  - Chronic disease: PCPs called on to meet growing health challenge.

PMID- 24730106
TI  - HIPAA: how to protect yourself and your practice.

PMID- 24730107
TI  - 10 apps physicians recommend to their patients.

PMID- 24730108
TI  - Understanding the new payment models.

PMID- 24730109
TI  - Are you documenting shared/split visits correctly?

PMID- 24730110
TI  - Medicare codes coming for telehealth, preventive care.

PMID- 24730111
TI  - Ancillary services: the prescription for a difficult business climate.

PMID- 24730112
TI  - Recalibrating the numbers.

PMID- 24730113
TI  - President's update: take a moment to breathe.

PMID- 24730114
TI  - RE: renewal.

PMID- 24730115
TI  - Renewal.

PMID- 24730116
TI  - Re: new AHS staffing models cause for concern.

PMID- 24730117
TI  - In response to Donna F.'s letter written to the editor in Fall 2013 edition of
      Alberta RN magazine.

PMID- 24730118
TI  - I would like to address Donna F's concerns re RNs.

PMID- 24730119
TI  - CNPS infoLaw: mobile devices in the workplace.

PMID- 24730120
TI  - What can be done about horizontal violence?

PMID- 24730121
TI  - Collaboration is key.

PMID- 24730122
TI  - Sleep on it: why sleep is just as important as diet and exercise when it comes to
      shift workers staying healthy.

PMID- 24730123
TI  - Becoming Florence.

PMID- 24730124
TI  - Aggregate analysis of oxytocin incidents.
AB  - Oxytocin is a valuable, time-tested drug and one of the most commonly used
      medications during labour and delivery.It acts on the smooth muscle of the uterus
      to stimulate contractions. In Canada, its uses include the induction of labour in
      patients with a medical indication for the initiation of labour; the stimulation
      and reinforcement of labour; and to control postpartum bleeding and hemorrhage.'
      As a high-alert medication, oxytocin bears a heightened risk of causing
      significant patient harm if used in error. For example, use of this drug to
      induce labour has been associated with significant adverse effects to both the
      mother (e.g., arrhythmias, uterine hyperstimulation, postpartum hemorrhage) and
      the fetus (e.g., bradycardia, hypoxia, hyperbilirubinemia, retinal
      hemorrhage).This bulletin shares information about incidents involving the use of
      oxytocin that have been voluntarily reported to the Canadian Medication Incident
      Reporting and Prevention System (CMIRPS). It includes an overview of the
      incidents and highlights major themes identified through a multi-incident
      analysis to raise awareness about continuous improvement opportunities for
      management of this medication.

PMID- 24730125
TI  - Closing perspectives RNs and NPs: our front line of patient advocacy.

PMID- 24730126
TI  - Characterization and mass spectrometry analysis of aminopeptidase N from
      Pseudomononas putida Lup.
AB  - An intracellular aminopeptidase N synthesized by Pseudomonas putida Lup was
      purified and characterized. The approx. 150-fold purified enzyme showed highest
      activity against A-beta-naphthylamide at pH 7.5 and at temperature 40 degrees C
      and was 100% thermostable for 240 min at 40 degrees C. P putida lup
      aminopeptidase N is a monomer with molecular mass approx. 99 kDa determined by
      SDS-PAGE and gel permeation chromatography. The enzyme has broad substrate
      specificity, but is the most active against protein substrates with N-terminal
      alanine and arginine. The activity of P. putida Lup aminopeptidase N is strongly
      inhibited in the presence of specific metallopeptidase inhibitors and is partly
      recovered in the presence of Zn2+ and Co2+ ions. Co2+, Mg2+ and Ca2+ ions
      increased the activity of the enzyme. Moreover, the enzyme was inhibited by
      inhibitors of cysteine enzymes. Analysis of fragments of the amino acid sequence
      of the purified enzyme demonstrated high similarity to PepN of Pseudomonas putida
      GB-1.

PMID- 24730127
TI  - Production of bacteriocin E50-52 by small ubiquitin-related modifier fusion in
      Escherichia coli.
AB  - Bacteriocin E50-52, a class IIa bacteriocin with a wide antibacterial spectrum,
      and has a huge potential to be a substitute for convention. antibiotics. In this
      research, the bacteriocin E50-52 gene was cloned into the expression vector pET
      SUMO (small ubiquitin-related modifier) and introduced into Escherichia coli BL21
      (DE3). The recombinant fusion protein SUMO-bacteriocin E50-52 expressed in a
      soluble form was purified to a purity of more than 90% by Ni-NTA sepharose column
      and 117 mg fusion protein was obtained per liter of fermentation culture. The
      fusion protein was cleaved with SUMO protease and re-applied to a Ni-NTA
      Sepharose column. Finally, about 16 mg recombinant bacteriocin E50-52 (rbE50-52)
      was obtained from a 1-liter fermentation culture with no less than 95% purity.
      The rbE50-52 had similar antimicrobial properties and molecular weight as the
      native bacteriocin E50-52 and showed very low hemolytic activity.

PMID- 24730128
TI  - Comparative study of PCR-based approaches for the genetic characterization of
      three strains of Acidithiobacillus caldus isolated from different sites in China.
AB  - Comparative study of the genetic characteristics among three Acidithiobacillus
      caldus strains isolated from different typical environments in China was
      performed using a combination of molecular methods, namely sequencing analysis of
      PCR-amplified 16S rRNA genes and 16S-23S rRNA gene intergenic spacers (ITS),
      repetitive element PCR (rep-PCR), arbitrarily primed PCR (AP-PCR) fingerprinting
      and random amplified polymorphic DNA (RAPD). Both of the 16S rRNA gene and 16S
      23S rRNA gene intergenic spacers sequences of the three strains exhibited small
      variations, with 99.9-100%, 99.7-100% identity respectively. In contrast,
      according to the analysis of bacterial diversity based on rep-PCR and AP-PCR
      fingerprinting, they produced highly discriminatory banding patterns, and the
      similarity values between them varied from 61.97% to 71.64%. RAPD analysis showed
      that banding profiles of their genomic DNA exhibited obvious differences from
      each other with 53.44-75% similarity. These results suggested that in contrast to
      16S rRNA genes and 16S-23S rRNA gene intergenic spacers sequencing analysis, rep
      PCR, AP-PCR fingerprinting and RAPD analysis possessed higher discriminatory
      power in identifying these closely related strains. And they could be used as
      rapid and highly discriminatory typing techniques in studying bacterial
      diversity, especially in differentiating bacteria within Acidithiobacillus
      caldus.

PMID- 24730129
TI  - Biological evaluation of quaternary bis ammonium salt and cetylpyridinum bromide
      against S. epidermidis biofilm.
AB  - Quaternary ammonium compounds are broad-spectrum bacteriocides widely used as
      antiseptics, disinfection and preservation agents. The aim of this study was to
      examine the activity of two quaternary ammonium salts, cetylpyridinum bromide and
      a newly synthesized quaternary bis ammonium salt, against S. epidermidis biofilm.
      The average values of killing efficiency for cetylpyridinum bromide ranged from
      26.6% to 64.1% for all tested concentrations (0.125 to 8.0 microg x mL(-1)) and
      for quaternary bis ammonium salt the percentage of killing efficiency ranged from
      59.7% to 88.4% for tested concentrations (from 2.0 to 128.0 microg x mL(-1)).
      Both tested compounds significantly affect staphylococcal biofilms, but any of
      used concentrations caused a total eradication of bacterial biofilm.

PMID- 24730130
TI  - The effect of nanosilver on pigments production by Fusarium culmorum (W. G. Sm.)
      Sacc.
AB  - A disk-diffusion method experiment assessed the impact of nanosilver on
      production of secondary metabolites (pigments) by the Fusarium culmorum fungus.
      Nanosilver colloidal particles in water have been obtained by the use of a method
      based on high voltage electric arcs between silver electrodes. The silver
      nanoparticles size in colloid ranged between 15 and 100 nm and 7, 35 and 70 ppm
      concentration. Nanosilver modifies the metabolism of the researched F. culmorum
      strain. Coming into contact with nanosilver colloids induces more intensive
      mycelia pigmentation correlated with nanosilver concentration levels. The
      performed analysis of metabolites indicates that under the influence of
      nanosilver fungi biosynthesise aurofusarin more intensively and the conversion of
      rubrofusarin to aurofusarin is intensified as compared to the control culture.
      Under the influence of nanosilver F. culmorum intensively biosynthesises an
      unidentified dye which shares structural features with aurofusarin but which is
      not produced by fungi in standard cultures.

PMID- 24730131
TI  - Possibilities in identification of genomic species of Burkholderia cepacia
      complex by PCR and RFLP.
AB  - The strains belonging to Burkholderia cepacia complex are important opportunistic
      pathogens in immunocompromised patients and cause serious diseases. It is
      possible to obtain isolates from soil, water, plants and human samples. Taxonomy
      of this group is difficult. Burkholderia cepacia complex consists of seventeen
      genomic species and the genetic scheme is based on recA gene. Commonly, first
      five genomovars occurre in humans, mostly genomovars II and III, subdivision
      IIIA. Within this study we tested identification of first five genomovars by PCR
      with following melting analysis and RFLP. The experiments were targeted on
      eubacterial 16S rDNA and specific gene recA, which allowed identification of all
      five genomovars. RecA gene appeared as more suitable than 16S rDNA, which enabled
      direct identification of only genomovars II and V; genomovars I, III and IV were
      similar within 16S rDNA sequence.

PMID- 24730132
TI  - Analysis of Proteus mirabilis distribution in multi-species biofilms on urinary
      catheters and determination of bacteria resistance to antimicrobial agents.
AB  - The objectives of the investigation presented in this paper were: to examine the
      frequency of P. mirabilis isolation from catheters and assess the complexity of
      multi-species biofilms which these bacteria form, as well as to determine the
      vulnerability of planktonic and sessile P. mirabilis populations to popular
      antibiotics and compare it to the susceptibility of other Gram-negative bacteria
      isolated as associated flora from multi-species biofilm. 88 urological catheters,
      collected from long-term catheterized patients were examined. Uropathogens were
      recovered from the catheter surface by sonication, and identified on standard
      diagnostic media. The broth-microdilution method and the MBEC High-throughput
      Screening assay were used to determine the bacterial resistance to antibiotics.
      279 microorganisms were isolated from 88 urinary catheter biofilms. The
      Enterobacteriaceae family were the most frequently detected bacteria (53.2% of
      isolates), whereas Proteus spp. isolation accounted for 17.9%, which placed these
      bacilli on the third position in the Enterobacteraceae family. Among all the
      tested drugs, amikacin and cephalosporins (ceftriaxone, cefotaxime and cefaclor)
      exhibited the highest activity against P. mirabilis planktonic cells, 86% and 73%
      of strains were susceptible to these antibiotics, respectively. 100% of P.
      mirabilis sessile forms were resistant to cefepime, ciprofloxacin, gatifloxacin,
      and norfloxacin. Amikacin and ceftriaxone affected only 5% of sessile forms. The
      planktonic cells of the other studied uropathogens were mostly vulnerable to the
      all tested drugs (exception P. aeruginosa strains), the most effective of which
      occurred to be amikacin and cefepime. Obtained MBECs values were 2-512-fold
      higher than MICs assessed for planktonic forms.

PMID- 24730133
TI  - Serotypes and antibiotic resistance of Streptococcus pneumoniae from adenoids in
      preschool children with recurrent upper respiratory tract infections.
AB  - We investigated children aged 2-5, who had gone adenoidectomy for recurrent
      and/or persistent symptoms of upper respiratory tract infections for prevalence
      of pneumococci in adenoid tissue. Serotypes and antibiotic resistance patterns of
      the isolated pneumococci were determined and also risk factors of pneumococcal
      colonization were defined. S. pneumoniae colonization in adenoids was found in 62
      (60.2%) children. Serotypes belonged to 10-valent and 13-valent pneumococcal
      conjugated vaccines (PCVs) constituted 56.1% and 68.2% of the isolates,
      respectively. Decreased susceptibility to penicillin was found in 45.5% of
      isolates; pneumococci were resistant to cotrimoxazole (62.1%), tetracycline
      (43.9%), erythromycin (54.5%), clindamycin (54.5%) and chloramphenicol (31.8%).
      Multidrug resistant S. pneumoniae comprised 57.6% of the isolates. Antibiotic
      resistant pneumococci were mostly distributed among serotypes belonged to 10
      valent and 13-valent PCVs. Good vaccine coverage among the isolated pneumococci
      confirmed that the introduction of PCVs in the national immunization programme
      may reduce the pool of resistant and multidrug resistant pneumococci in a
      community.

PMID- 24730134
TI  - Iron bacterial phylogeny and their execution towards iron availability in
      Equatorial Indian Ocean and coastal Arabian Sea.
AB  - Based on distinct colony morphology, color, size, shape and certain other traits,
      92 bacterial isolates were investigated to understand their managerial ability on
      iron from the Arabian Sea and Equatorial Indian Ocean samples. The ARDRA
      (amplified rDNA restriction analysis) applied to eliminate the duplication of the
      bacterial strains, resulted 39 different banding patterns. The 16S rRNA gene
      sequencing data indicate the dominancy of three phylogenetic groups, alpha
      Proteobacteria (10.25%), gamma-Proteobacteria (35.89%) and Bacilli (53.84%) in
      these waters. Marinobacter and Bacillus were the only common genera from both of
      the regions. Pseudoalteromonas, Halomonas, Rheinheimera, Staphylococcus and
      Idiomarina were some of the other genera obtained from the Arabian Sea.
      Erythrobacter, Roseovarius, Sagittula and Nitratireductor were found mostly in
      Equatorial Indian Ocean. In addition, 16S rRNA gene sequence data of some of our
      iron bacterial strains belong to novel species and one isolate ASS2A could form a
      new genus. Close to 23% of the isolates were able to produce high affinity sets
      of ligands like siderophores to mediate iron transport into the cell. The current
      study indicated that the Equatorial Indian Ocean species were well adapted to
      oxidize iron as an electron acceptor and the Arabian Sea species preferably go
      through siderophore production.

PMID- 24730135
TI  - Characterization of Klebsiella pneumoniae strains isolated from urinary tract
      infections: detection of ESBL characteristics, antibiotic susceptibility and RAPD
      genotyping.
AB  - In this study, a hundred Klebsiella pneumoniae strains isolated from urinary
      tract infections were evaluated in terms of genotyping, susceptibility to certain
      antibiotics and detection of extended spectrum of beta lactamase (ESBL)
      production. The random amplified polymorphic DNA (RAPD-PCR) method was used to
      identify the genetic differentiation of K. pneumoniae isolates. A total of 26
      different DNA bands ranging between 334 bp and 28033 bp were detected among the
      strains. It was found that 100 K. pneumoniae strains revealed 11 different RAPD
      profiles. Antibiotic susceptibility tests were conducted using a disc diffusion
      method against 16 antibiotics. Fifty-five different resistance profiles were
      determined among the strains. ESBL-productions of the strains were determined by
      the double disc synergy test (DDST) and ESBL E-test methods. ESBL production
      rates among the strains were found to be 55% by E-test method and 45% by DDST
      method. While ESBL-producing K. pneumoniae strains showed the greatest resistance
      to penicillin G (100%), followed by piperacillin (92.7%) and erythromycin
      (85.4%),the resistance rates of non ESBLproducing strains to those antibiotics
      were determined as 97.8%, 88.8% and 88.8%, respectively. Both groups of strains
      showed the highest sensitivity to meropenem. Based on the results obtained from
      the study, it was concluded that the detection of ESBL-producing strains by the E
      test method was more sensitive than by the DDST method. Phenotypic and genotypic
      identification methods should be used together to detect ESBL presence. The RAPD
      PCR method alone will not be adequate in the genotyping of the strains and
      alternative DNA-based methods should be used.

PMID- 24730136
TI  - Screening, characterization and biofilm formation of nickel resistant bacteria
      isolated from indigenous environment.
AB  - Nickel resistant bacteria (ZB, ZC, ZD, ZL, ZK and S1X) were isolated from
      industrial effluents and corroded iron pieces from indigenous environment of
      Punjab, Pakistan. These six strains could tolerate nickel at different levels
      with ZB, ZC, ZD, ZL, ZK, and S1X having 233, 225, 267, 233, 228 and 296 mM
      minimum inhibitory concentration (MIC) of nickel ions, respectively. These
      bacteria were sensitive to Cu(+2), Cr(+3), Co(+2), and Al(+3) as they did not
      grow even in the presence of 1 mM concentration of all these ions in minimal
      medium, whereas all of them were resistant to Fe3 upto 1.3 mM in minimal medium.
      The best appropriate temperature for nickel resistant bacteria was 37 degrees C
      and all of them showed maximum growth at pH 8. These bacteria were characterized
      morphologically and biochemically. Biofilm forming ability of the bacteria was
      checked with and without nickel stress and it was found that strains ZK and S1X
      were able to form a compact biofilm even under nickel stress. The sequencing of
      16S rRNA-encoding genes from these nickel resistant bacteria showed that they
      belonged to four different genera namely, Klebsiella, Pseudomonas, Bacillus and
      Cronobacter.

PMID- 24730137
TI  - Phylogenetic and biochemical characterization of a new halo-thermotolerant,
      biofilm-forming Bacillus from Saline Lake of Iran.
AB  - In this study, five halotolerant Bacillus isolates from Aran-Bidgol Saline Lake
      in Iran were identified from saline environments. Screening of the bacteria led
      to the identification of a unique halo-thermotolerant Bacillus. On the basis of
      genetic and phenotypic data, this isolate was closely related to Bacillus
      licheniformis. But isolated Bacillus can be distinguished from B. licheniformis
      by salt tolerance, 16S rDNA sequence and some different physicochemical
      properties. Thus, suggested that the isolate was not the known Bacillus. Optical
      density analysis indicated strong biofilm formation for this strain. Also this
      isolate exhibited average tolerance to 1-25 mM concentrations of zinc and was
      sensitive to all concentrations of nickel. In biosurfactant production assay,
      this Bacillus exhibited the high activity for semi-quantitative oil displacement
      test (3.14 +/- 0.02 cm2) and evaluated positive for drop-collapse test and
      hemolytic activity. Moreover, amylase, protease and DNase enzymes produced in
      presence of 10-20% salt of medium. Therefore, identified Bacillus could supply
      potential microbial materials for bioremediation purposes and biotechnological
      applications.

PMID- 24730138
TI  - Carriage of group B streptococci in pregnant women from the region of Krakow and
      their antibiotic resistance in the years 2008-2012.
AB  - The aim of the study was a retrospective analysis of the frequency of group B
      streptococci (Streptococcus agalactaie; GBS) carriage in pregnant women from the
      region of Krakow, together with an analysis of their drug resistance, carried out
      between 2008-2012. The study included 3363 pregnant women between 35 and 37 weeks
      of gestation, studied in accordance with the guidelines of the Polish
      Gynecological Society (2008). A high percentage of pregnant women who are
      carriers of group B streptococci was demonstrated. Each year covered by the
      study, it was in the range of 25-30%, with an average value equal to 28%. The
      results confirm the need for taking swabs from both the vagina and anus, since
      15% of GBS-positive patients showed only rectal carriage. High percentage of
      isolates resistant to erythromycin was detected, which ranged from 22% to 29%,
      with an average value equal to 25%, as well as a high proportion of isolates
      resistant to clindamycin being 17-25%, with an average of 20%. The results
      indicate the need to standardize the methodology of collecting samples for GBS
      testing and introduce microbiological diagnostic standards in all gynecological
      and obstetric centers in Poland, in order to carry out a detailed epidemiological
      analysis in our country.

PMID- 24730139
TI  - A case of a late and atypical knee prosthetic infection by no-biofilm producer
      Pasteurella multocida strain identified by pyrosequencing.
AB  - Prosthetic joint infections due to Pasteurella multocida are rarely but
      increasingly reported but no data on production of biofilm are available. We
      report the case of a woman with a late, haematogenous peri-prosthetic infection
      of cemented total knee arthroplasty caused by a strain of P. multocida identified
      by pyrosequencing and unable to produce biofilm. Comparison of clinical and
      laboratory findings with those reported in other patients evidenced differences
      mainly in the period of symptoms' onset and in the behaviour of some inflammatory
      markers.

PMID- 24730140
TI  - Application of a real-time PCR method for Salmonella spp., Escherichia coli,
      Staphylococcus aureus and Clostridium perfringens detection in water samples.
AB  - The diagnostic assessment of water sanitary state is based mainly on the
      cultivation of bacteria retained on membrane filters. However classical
      microbiology methods have a lot of disadvantages. More and more frequently, rapid
      detection and identification of pathogens present in water is based on molecular
      biology techniques. The aim of this study was to determine the effectiveness and
      usefulness of a real-time PCR method, when compared to the recommended bacteria
      culture method, in diagnostics of pathogens in water samples. The research
      concerned the detection and identification of main sanitary indicators of water
      such as: Salmonella spp., Escherichia coli, Staphylococcus aureus and Clostridium
      perfringens. The analyses were conducted in water samples contaminated with the
      reference material (the aforementioned bacteria) and real environmental samples,
      which were examined for the presence of nucleic acid of: Salmonella spp., E.
      coli, S. aureus and C. perfringens using a real-time PCR method.

PMID- 24730141
TI  - The influence of the organic matter of sewage sediments on biological activity of
      microorganisms which carry out the transformations of carbon and nitrogen
      compounds.
AB  - Soil microorganisms play an important role in the organic matter transformation
      process. The soil microorganisms also are in symbiotic relationship with plants.
      At the same time, soil microorganisms are sensitive to both anthropogenic and
      natural habitat changes. Particular characteristics of organic matter (the C:N
      relation, pH, the content the content of assimilated nutrients, the xenobiotics
      etc.) modify the biotic conditions of the soils. This particularly concerns the
      microorganisms which carry out the changes in the mineral and organic nitrogen
      compounds and the transformation of the external organic matter. The first aim of
      this work was to assess the influence of the sewage sediments and the manure on
      the phytosanitary potential of the soil environment. The second aim of this
      article was to estimate the number and activity of microorganisms which carry out
      the transformation of carbon and nitrogen compounds. This work showed the
      stimulating effect of the external organic matter both on the number and on the
      activity of most of the physiological groups. The manure mainly stimulated
      ammonificators, amylolitic microorganisms and Azotobacter sp. The sewage
      sediments mainly stimulated ammonificators, nitrifiers of I phase and
      cellulolytic microorganisms. The statistically significant impact of the physio
      chemical soil habitat on the biological activity of the analyzed groups of
      microbes was also noted.

PMID- 24730142
TI  - Fast identification of Yersinia pestis, Bacillus anthracis and Francisella
      tularensis based on conventional PCR.
AB  - Rapid and accurate diagnostic tools for detection and identification of Y pestis,
      B. anthracis and F. tularensis are essential for timely initial appropriate
      treatment of exposed individuals, which will be critical to their survival, as
      well as for reduction of the public health impact and the spread of the disease.
      The paper presents application of fast polymerases and fast dry electrophoresis
      in conventional PCR as an alternative for real-time PCR application for detection
      and identification of the above pathogens. The proposed method takes less than 50
      min. to obtain final results of the tests and is cheaper than real-time PCR.

PMID- 24730143
TI  - Response of soybean to seed inoculation with Bradyrhizobium japonicum and with
      mixed inoculants of B. japonicum and Azotobacter chroococcum.
AB  - Effects of pre-sowing soybean seed inoculation with Bradyrhizobium japonicum
      alone or with mixed inoculants containing soybean rhizobia and Azotobacter
      chroococcum were compared. In the pot experiment all the tested strains of
      soybean rhizobia in pure cultures or in mixtures with A. chroococcum
      significantly improved nodulation of soybean plants and seed yields of this crop.
      In micro-plot experiments pre-sowing soybean seeds treatment with the inoculant
      containing the most effective strain 94P of B. japonicum alone or with the mixed
      inoculant of strain 94P and A. chroococcum were equally effective in improving
      nodulation intensity and seed yields of soybean in comparison to the uninoculated
      soybean.

PMID- 24730144
TI  - Association of untypeable enteropathogenic Escherichia coli (EPEC) strains with
      persistent diarrhea in children from the region of lower Silesia in Poland.
AB  - Enteropathogenic Escherichia coli strains (EPEC) carrying the eae gene encoding
      intimin are divided into typical strains producing bundle forming pili, encoded
      by the bfpA gene, and atypical strains lacking the gene. In the study typical and
      atypical EPEC that did not agglutinated with EPEC polyvalent antisera but
      carrying virulence factors characteristic to other pathogenic E. coli i.e.
      diffusely adhering and enteroaggregative E. coli were isolated from 24 (43.6%) of
      55 children > 10 years old with persistent diarrhea. These results indicated that
      non-typeable typical and atypical EPEC can contribute to chronic intestinal
      infections in teenagers.

PMID- 24730145
TI  - CAMP test detected Staphylococcus delphini ATCC 49172 beta-haemolysin production.
AB  - Through a CAMP test, we first observed a Staphylococcus delphini strain (ATCC
      49172) to release beta-haemolysin. Production of the latter in this coagulase
      positive species of the 'Staphylococcus intermedius Group', in fact, has been
      labeled to be undetermined, thus far. Of course, a wider number of strains have
      to be investigated in order to define whether this property is constitutive (like
      in Staphylococcus (pseud)intermedius), or strain-dependent (like in
      Staphylococcus aureus), and which clinical impact it has; nevertheless, we can
      state that S. delphini ATCC 49172 indeed produces this toxin.

PMID- 24730146
TI  - Hospitals plan for lasting declines in admissions.

PMID- 24730147
TI  - Enrollment on small-business exchanges runs far behind expectations.

PMID- 24730148
TI  - AIDS patients in Louisiana may lose insurance over anti-kickback laws.

PMID- 24730149
TI  - Making physicians pay off.

PMID- 24730150
TI  - Health IT survey. Double trouble.

PMID- 24730151
TI  - Tardy EHR upgrades loom as one of many Stage 2 challenges.

PMID- 24730152
TI  - Organizations' IT spending expected to keep growing.

PMID- 24730153
TI  - Bush's goal. U.S. won't meet universal EHR deadline, many say.

PMID- 24730154
TI  - Funding the RECs. Extension centers 'a great investment,' leaders say.

PMID- 24730155
TI  - To pay for a doc fix, focus on post-acute care.

PMID- 24730156
TI  - HIMSS aims to transform healthcare.

PMID- 24730157
TI  - Personal health technology can improve outcomes.

PMID- 24730158
TI  - Moving physicians from fee-for-service first step to 'doc fix,' mcClellan says.

PMID- 24730159
TI  - Largest children's hospitals. Ranked by number of staffed beds.

PMID- 24730160
TI  - Acute care. Policymakers see hospital chains as the NHS's missing link.

PMID- 24730161
TI  - Access to patient data is key to NHS survival. Mining patient data will close
      knowledge gap.

PMID- 24730162
TI  - There is no easy fix for successful leadership.

PMID- 24730163
TI  - Be bold and commit to integration.

PMID- 24730164
TI  - Regulators rule... but is that ok?

PMID- 24730165
TI  - Mental health. Why wait to make psychiatric interventions?

PMID- 24730166
TI  - Patient experience. Integrated care under the microscope.

PMID- 24730167
TI  - If you want to motivate someone, shut up already.

PMID- 24730168
TI  - The culture to cultivate.

PMID- 24730169
TI  - Connect, then lead.
AB  - In puzzling over whether it's better to be feared or loved as a leader,
      Machiavelli famously said that, because it's nigh impossible to do both, leaders
      should opt for fear. Research from Harvard Business School's Amy Cuddy and
      consultants Matthew Kohut and John Neffinger refutes that theory, arguing that
      leaders would do much better to begin with "love"--that is, to establish trust
      through warmth and understanding. Most leaders today approach their jobs by
      emphasizing competence, strength, and credentials. But without first building a
      foundation of trust, they run the risk of eliciting fear, resentment, or envy.
      Beginning with warmth allows trust to develop, facilitating both the exchange and
      the acceptance of ideas--people really hear your message and become open to it.
      Cultivating warmth and trust also boosts the quantity and quality of novel ideas
      that are produced. The best way to gain influence is to combine warmth and
      strength--as difficult as Machiavelli says that may be to do. In this article,
      the authors look at research from behavioral economics, social psychology, and
      other disciplines and offer practical tactics for leaders hoping to project a
      healthy amount of both qualities.

PMID- 24730170
TI  - The network secrets of great change agents.
AB  - Change is hard, especially in a large organization. Yet some leaders succeed-
      often spectacularly--at transforming their workplaces. what makes them able to
      exert this sort of influence when the vast majority can't? The authors tracked 68
      change initiatives in the UK's National Health Service, an organization whose
      size, complexity, and tradition can make reform difficult. They discovered
      several predictors of change agents' success--all of which emphasize the
      importance of networks of personal relationships: Change agents who were central
      in the organization's informal network had a clear advantage, regardless of their
      position in the formal hierarchy. People who bridged disconnected groups or
      individuals were more effective at implementing dramatic reforms. The resisters
      in their networks did not necessarily know one another and so were unlikely to
      form a coalition. Change agents with cohesive networks, in which all individuals
      were connected, were better at instituting minor changes. Their contacts rallied
      around the initiative and helped convince others of its importance. Being close
      to people who were ambivalent about a change was always beneficial. In the end,
      fence-sitters were reluctant to disappoint a friend. But close relationships with
      resisters were a double-edged sword: Such ties helped push through minor
      initiatives but were a hindrance when attempting major change.

PMID- 24730171
TI  - How experts gain influence.
AB  - In theory, the risk management groups of two British banks--Saxon and Anglo--had
      the same influence in their organizations. But in practice, they did not: Saxon's
      was engaged in critical work throughout the bank, while Anglo's had little
      visibility outside its areas of expertise. In their study of these two financial
      institutions, the authors identified four competencies--trailblazing, toolmaking,
      teamwork, and translation--that help functional leaders or groups compete for top
      management's limited attention and increase their impact. Anglo's risk managers
      were strong in only some of the competencies, but Saxon's were strong in all
      four. They consistently scanned the internal and external environment for
      important issues to which they could apply a risk management perspective
      (trailblazing) and then developed tools--such as quarterly risk reports--that
      spread their expertise (toolmaking). While controlling the tools' design and
      implementation, the risk managers incorporated business managers' insights
      (teamwork) and made sure everyone could understand the findings (translation).
      Ultimately, experts' roles must fit the organization's strategy and structural
      needs. In some situations, functional experts can raise their profile by
      cultivating just two of the competencies. But those who are strong in all four
      are likely to be the most influential.

PMID- 24730172
TI  - The uses (and abuses) of influence.
AB  - The ability to persuade others to contribute to your efforts is a key skill for
      managers, for team members--for anyone who wants to elevate the probability of
      success. Research by leading social scientist Robert Cialdini has found that
      persuasion works by appealing to certain deeply rooted human responses: liking,
      reciprocity, social proof, commitment and consistency, authority, and scarcity.
      In this edited interview with HBR's executive editor, Cialdini expands on the six
      principles of persuasion and how leaders can make effective, authentic use of
      them in everyday business situations. He also previews findings from new research
      on the ethics of influence and how dishonesty affects individuals and the
      organization.

PMID- 24730173
TI  - Your brain at work. What a new approach to neuroscience can teach us about
      management.
AB  - Recently, technological advances have led neuroscientists to develop a new and
      more sophisticated framework. It shifts the focus of study from the activity of
      specific brain regions to how networks of brain regions activate in concurrent
      patterns. In this article, two experts in brain science explain important
      discoveries that have been made about four key networks: the default network,
      which is engaged in introspection and in imagining a different time, place, or
      reality; the reward network, which activates in response to pleasure; the affect
      network, which plays a central role in emotions; and the control network, which
      is involved in understanding consequences, impulse control, and selective
      attention. These discoveries hold major implications for managers. In particular,
      they shed light on: the best way to generate "Eureka!" thinking. What motivates
      employees. Whether you should trust your gut and listen to your emotions in
      decision making. The opportunities and pitfalls of multitasking. These insights
      are just the beginning, say the authors, who believe that a hugely productive
      dialogue between neuroscience and business will develop as more findings emerge.

PMID- 24730174
TI  - Leadership lessons from the Chilean mine rescue.
AB  - Three years ago, when a cave-in at the San Jose mine in Chile trapped 33 men
      under 700,000 metric tons of rock, experts estimated the probability of getting
      them out alive at less than 1%. Yet, after spending a record 69 days underground,
      all 33 were hoisted up to safety. The inspiring story of their rescue is a case
      study in how to lead in situations where the stakes, risk, and uncertainty are
      incredibly high and time pressure is intense. Today executives often find
      themselves in similar straits. When they do, many feel torn. Should they be
      directive, taking charge and commanding action? Or should they be empowering,
      enabling innovation and experimentation? As the successful example of Andre
      Sougarret, the chief of the mine rescue operation, shows, the answer is yes--to
      both. The choice is a false dichotomy. Implementing this dual approach involves
      three key tasks. Each has directive and enabling components. The first task is
      envisioning, which requires instilling both realism and hope. The second task is
      enrolling, which means setting clear boundaries for who is on and off the team,
      but inviting in helpful collaborators. The third task is engaging--leading
      disciplined execution while encouraging innovation and experimentation. The
      authors of this article describe how Sougarret ably juggled all of these tasks,
      orchestrating the efforts of hundreds of people from different organizations,
      areas of expertise, and countries in an extraordinary mission that overcame
      impossible odds.

PMID- 24730175
TI  - Working out when it hurts: how to exercise when you have chronic pain.

PMID- 24730176
TI  - On the level: is "brittle diabetes" a condition or a consequence of not having
      the right treatment?

PMID- 24730177
TI  - In the beginning: how to help your loved one accept a new diagnosis.

PMID- 24730178
TI  - Building a better pancreas: researchers are putting artificial-pancreas
      prototypes into real-world settings.

PMID- 24730179
TI  - The persuader for volunteer Gina Gavlak, the personal really is political.

PMID- 24730180
TI  - Lord of the ring: Paul Binder juggles diabetes and life with the big apple
      circus.

PMID- 24730181
TI  - Super woman: Sia Figiel wants to help people with diabetes soar.

PMID- 24730182
TI  - Double takes.

PMID- 24730183
TI  - What should I eat? On the trail of the elusive diabetes diet.

PMID- 24730184
TI  - Fat facts. should you eat less or more fat? Well it depends.

PMID- 24730185
TI  - Sole food: ADA collaboration brings food, shoes, and diabetes awareness.

PMID- 24730186
TI  - Success stories: studying long lives with diabetes for clues to avoiding
      complications.

PMID- 24730187
TI  - The things that do not change.
AB  - This issue of Creative Nursing introduces our 2014 theme of Timeless Wisdom,
      cites each author's contribution to expanding our understanding of Ways of
      Knowing, and invites article submissions from all walks of nursing life.

PMID- 24730188
TI  - Kaleidoscopes of reality.
AB  - This article addresses the broad context of shifting definitions of how knowledge
      and reality can be described, including the transition from positivism to
      postpositivism in the 20th century. It provides an exploration of ways of
      knowing, from ancient Greek and yogic traditions to Barbara Carper's Fundamental
      Patterns of Knowing in Nursing (1978). It examines three reported components of
      modern care (intuition, cultural knowing, and spirituality) which are
      simultaneously present and absent in nursing. It concludes with an imaginative
      exploration of how nursing might be changed by transdisciplinary scholarship and
      education, new knowledge creation through interactive online communities, and the
      emergence of collective wisdom.

PMID- 24730189
TI  - What lies within: phenomenology and intuitive self-knowledge.
AB  - This article discusses the significance of intuitiveness as a component of
      phenomenological knowing and demonstrates how this way of knowing may exist
      independently of or coexist collaboratively with rationality and evidence-based
      practice. By using a holistic approach to knowing, nurses use clinical reasoning
      skills to prevent adverse patient outcomes from failure to diagnose problems, to
      establish appropriate treatments, and/or to deal with complications. As the
      complexity of health care escalates, health care providers must strive to think
      holistically to advance knowledge and contribute to their discipline. The
      discipline of nursing requires holistic thought and innovative interventions.

PMID- 24730190
TI  - How experienced practitioners gain knowledge.
AB  - An evolution in nursing in the United Kingdom in the 1970s from rule-bound toward
      holistic, autonomous practice engendered an examination of nursing's body of
      knowledge and how it is incorporated into practice. This article describes
      Barbara Carper's (1978) Fundamental Patterns of Knowing in Nursing (empiric,
      ethical, aesthetic, and personal knowledge), and links it to three major
      worldviews of the way in which knowledge is sought (positivism, naturalism, and
      critical social theory). Carper's model was used in the United Kingdom as the
      basis for a curriculum of structured reflective practice using workshops,
      journaling, and clinical supervision. An example from a practitioner's diary
      demonstrates how Carper's model informs reflection on an interaction with a
      patient with newly diagnosed cancer.

PMID- 24730191
TI  - The wisdom of indigenous healers.
AB  - The wisdom of indigenous peoples is manifest in ways of knowing, seeing, and
      thinking that are passed down orally from generation to generation. This article
      takes the reader on a journey through three distinct ways of knowing,
      specifically as they relate to healing and health. The authors are a
      Midewanniquay, or Water Woman, of the Ojibway-Anishinabe people of the upper
      Midwest in the United States and Canada; a Iomilomi healer from Hawaii; and an
      initiated Priest in the Yoruba tradition of West Africa. The philosophies of all
      three cultures emphasize the importance of spirituality to health and wellbeing
      (or healing process), but each has unique ways in which it nurtures relationship
      with the Creator, the earth, and humankind through sacred rituals and healing
      practices.

PMID- 24730192
TI  - A midrange theory of empowered holistic nursing education: a pedagogy for a
      student-centered classroom.
AB  - The purpose of this article is to propose Empowered Holistic Nursing Education
      (EHNE) as a midrange theory--developed through induction, explication, deduction,
      and retroduction--to help nurse educators teach holistically and create a student
      centered classroom, to establish a theoretical basis for a nursing pedagogy
      reflecting nursing's foundational principles, and to guide future research. The
      model's 5 core concepts, how to use the model as a pedagogy for practice, and its
      application to research will be presented. Holistic nursing will be defined, and
      traditional holistic nursing, holistic pedagogy, and emancipatory pedagogy will
      each be described.

PMID- 24730193
TI  - Ways of knowing: a nurse and a physician discuss clinical decisions, actions, and
      lessons.
AB  - The authors, both experienced clinicians, met to discuss multiple and diverse
      ways of knowing in the clinical setting. How do we know what we know? Can we
      tease out the lessons we have learned from our experience in a sufficiently
      creative way so that we can apply them to new clinical situations and nurture the
      next generations of nurses and physicians- and our colleagues-with those
      insights? This article is a record of that discussion.

PMID- 24730194
TI  - Seeing the forest and the trees: increasing nurse practitioner students'
      observational and mindfulness skills.
AB  - Accurate, objective observation is a critical component of clinical diagnosis and
      patient management, which in turn is essential for successful diagnostic
      reasoning by advanced practice nurses. The purpose of this quasi-experimental
      study was to enhance nurse practitioner students' observation and reflective
      thinking skills using Looking Is Not Seeing, a reflective practice/experiential
      learning technique that uses art objects to teach observation (Pellico,
      Friedlaender, & Fennie, 2009). Students' posttest observation and interpretation
      scores showed statistically significant improvement over pretest scores.
      Students' mindfulness scores and their own perceived observational and
      interpretive ability were statistically significantly higher after participating
      in the study. Building on the established record of successful visual literacy
      programs for nursing and medical students at other institutions, this research
      can help educators implement the Looking Is Not Seeing pedagogy.

PMID- 24730195
TI  - [Prevention of arterial diseases in the 2010s: the European treatment guideline].
AB  - Reduction of risk factors at the population level forms the basis of the European
      recommendation of 2012 for the prevention of arterial diseases. Actions at the
      individual level arise from risk assessment. The risk of arterial disease is
      graded into four categories, the uppermost ones comprising patients who have
      already developed the disease, diabetics, those suffering from renal
      insufficiency and those carrying a serious gene defect. In Finland the risk among
      healthy people is assessed by using the FINRISKI tool. Non-smoking, healthy diet
      and regular exercise are suitable for all. Statins are an effective and safe
      means of prevention for those at high risk regardless of lipid values.

PMID- 24730196
TI  - [Long-term effects of uterine cesarean section scar].
AB  - During the last few decades the cesarean delivery rate has been around 15% in
      Finland. It has remained moderate compared with USA where 30% of women deliver by
      cesarean section. Compared with vaginal delivery, cesarean section is associated
      with a three- to sixfold risk of severe complications. Furthermore, it increases
      also long term gynecological morbidity, including intermenstrual bleeding,
      chronic pelvic pain and risk of secondary infertility. Scar pregnancy, uterine
      rupture, placenta previa and accrete are known risks after cesarean section.
      Because cesarean delivery is associated with increased long-term morbidity, the
      decision of performing cesarean section should always be carefully considered.

PMID- 24730197
TI  - [Autoimmune encephalitis as a cause of psychosis].
AB  - Antibodies directed to the surface structures of nerve cells may cause autoimmune
      encephalitis. It may cause limbic encephalitis requiring intensive care, or
      symptoms are restricted to psychosis. This disease may be impossible to
      distinguish clinically from a functional psychotic illness. Some of the cases are
      paraneoplastic, i.e. associated with a diagnosed or latent malignant neoplasia,
      most commonly ovarian teratoma. The first line treatment for autoimmune
      encephalitis is an immunomodulatory combination therapy with immunoglobulin and
      methylprednisolone. We recommend screening of the most common NMDAR and VGKC
      antibodies related to autoimmune encephalitis from patients having developed a
      new psychosis.

PMID- 24730198
TI  - [Antireflux surgery more cost-effective than medication after all?].
AB  - Although fundoplication has been found effective in the treatment of reflux
      disease, its long-term results have raised doubts due to the large number of
      patients taking acid blocker medication after the operation. Based on the five
      year follow-up of the REFLUX study, reflux symptoms and quality of life
      associated with reflux were improved after the operation. Laparoscopic
      fundoplication was found to be a cost-effective form of treatment among those
      having a chronic reflux disease. The operation can be recommended for treating
      reflux disease in patients exhibiting a non-optimal PPI drug response.

PMID- 24730199
TI  - [How can a doctor meet an anxious patient?].
AB  - A doctor can meet an anxious patient and handle her/his own reactions emerging in
      the therapeutic relationship. It is especially necessary to focus attention on
      the phenomena of the therapeutic relationship if the problems are prolonged and
      the patient and the doctor feel burdened. Mindfulness refers to conscious
      directing of alertness to the present, and to the approval and permissive
      perception of both extrinsic and intrinsic events (e.g. thoughts and feelings).
      The therapeutic relationships of a doctor may be affected by the doctor's
      presence and willingness to encounter her/his own reactions.

PMID- 24730200
TI  - [Treatment of anterior cruciate ligament rupture].
AB  - Anterior cruciate ligament rupture of the knee is a common knee injury associated
      with sports and exercise. The injury typically arises when the foot is tightly
      locked against the floor or ground, whereby a sudden change of direction combined
      with the slowed motion causes a rotary motion of the upper part of the tibia and
      a force rupturing the cruciate ligament. Approximately 30% of the injuries take
      place during a situation of direct contact. The instability of the knee due to
      the rupture may be strongly invalidizing. In such case surgical therapy is
      required, if appropriate conservative treatment does not lead to a good result.

PMID- 24730201
TI  - [From the disease-based assessment of work ability and functional capacity to a
      multidimensional assessment mode].
AB  - BACKGROUND. Doctors assess an individual's work ability by comparing the
      diagnoses and findings to the demands of work. The accuracy of this disease-based
      orientation has recently been challenged. METHODS. A case study was conducted to
      compare a disease-based and a multidimensional functioning -based work ability
      assessment, illustrated through an individual case. RESULTS. Relevant potential
      for promoting work ability was missed by the disease-based approach, evaluating
      the entitlement to social security benefits. In the assessment based on
      multidimensional functioning, dialogue-based plans were made to improve fitness
      for work. CONCLUSIONS. Multidimensional functioning is recommended as the basis
      of assessing work ability.

PMID- 24730202
TI  - [Epiglottitis and necrotizing mediastinitis in a middle-aged man].
AB  - Acute epiglottitis is nowadays a rare bacterial infection. Airway management and
      promptly started antimicrobial medication are essential in the treatment.
      Descending necrotizing mediastinitis is a life-threatening bacterial infection
      that typically spreads from an odontogenic, pharyngeal or neck infection. Despite
      the vagueness of symptoms, diagnosis must be made quickly. Owing to the high
      mortality rate, aggressive surgical treatment is indicated.

PMID- 24730203
TI  - [Update on current care guideline: sepsis (adults].
AB  - The incidence of severe sepsis and septic shock requiring intensive care in
      Finnish adult population has increased to 0.60 11000 /y. Despite improved
      prognosis, hospital mortality related to severe sepsis and septic shock is high
      24.1%. Key recommendations include prompt administration of antimicrobial
      therapy, optimally after blood cultures, quantitative fluid resuscitation and
      imaging studies to identify possible source of infection. Crystalloids are
      suitable for fluid resuscitation. Norepinephrine is the first-choice vasopressor
      in septic shock. Hydrocortisone should be considered only if fluid and
      vasopressor treatment does not restore hemodynamics.

PMID- 24730204
TI  - Editorial: Helping health care organizations to define diagnostic errors as
      missed opportunities in diagnosis.

PMID- 24730205
TI  - The next organizational challenge: finding and addressing diagnostic error.
AB  - BACKGROUND: Although health care organizations (HCOs) are intensely focused on
      improving the safety of health care, efforts to date have almost exclusively
      targeted treatment-related issues. The literature confirms that the approaches
      HCOs use to identify adverse medical events are not effective in finding
      diagnostic errors, so the initial challenge is to identify cases of diagnostic
      error. WHY HEALTH CARE ORGANIZATIONS NEED TO GET INVOLVED: HCOs are preoccupied
      with many quality- and safety-related operational and clinical issues, including
      performance measures. The case for paying attention to diagnostic errors,
      however, is based on the following four points: (1) diagnostic errors are common
      and harmful, (2) high-quality health care requires high-quality diagnosis, (3)
      diagnostic errors are costly, and (4) HCOs are well positioned to lead the way in
      reducing diagnostic error. FINDING DIAGNOSTIC ERRORS: Current approaches to
      identifying diagnostic errors, such as occurrence screens, incident reports,
      autopsy, and peer review, were not designed to detect diagnostic issues (or
      problems of omission in general) and/or rely on voluntary reporting. The
      realization that the existing tools are inadequate has spurred efforts to
      identify novel tools that could be used to discover diagnostic errors or
      breakdowns in the diagnostic process that are associated with errors. New
      approaches--Maine Medical Center's case-finding of diagnostic errors by
      facilitating direct reports from physicians and Kaiser Permanente's electronic
      health record--based reports that detect process breakdowns in the followup of
      abnormal findings--are described in case studies. CONCLUSION: By raising
      awareness and implementing targeted programs that address diagnostic error, HCOs
      may begin to play an important role in addressing the problem of diagnostic
      error.

PMID- 24730206
TI  - Glycemic control mentored implementation: creating a national network of shared
      information.
AB  - BACKGROUND: The Society of Hospital Medicine's (SHM's) Glycemic Control Mentored
      Implementation (GCMI) program, which, like all MI programs, is conducted as an
      improvement collaborative, is intended to help hospitals improve inpatient
      glycemic control in diabetic and nondiabetic patients by educating and mentoring
      quality teams. METHODS: Hospital quality improvement (QI) teams applied for
      participation in GCMI from 2009 through 2012. Accepted sites were assigned either
      a hospitalist or endocrinologist mentor to work through the life cycle of a QI
      project. SHM's Implementation Guide, online resources, measurement strategies,
      Web-based Glycemic Control Data Center for Performance Tracking, webinars,
      interactive list-serve, and other tools help mentors guide these teams through
      the program. Mentors in GCMI bring expertise in both inpatient glycemic control
      and QI. RESULTS: One hundred fourteen hospital QI teams were enrolled into the
      GCMI program in the course of 2.5 years. Of these 114 sites, 90 completed the
      program, with 63 of them uploading data to the Data Center. Feedback from the
      sites was consistently positive, with the listserve, Data Center, and mentorship
      reported as the top three most effective components of the program. Ninety-five
      percent of respondents stated that they would recommend participation in an SHM
      mentored implementation program to a colleague. Participants reported improved
      leadership skills and increased institutional support for glycemic control.
      CONCLUSIONS: Hospital quality teams participating in the GCMI program gained
      support to overcome barriers, focus on improving glycemic control, network with
      peers and expert mentor physicians, collect and analyze data, and build quality
      leaders. The features and structure of this program can be used in other
      multisite QI goals and projects.

PMID- 24730207
TI  - Long-term safety and efficacy of a universal nursing-run intravenous insulin
      guideline.
AB  - BACKGROUND: Despite the plethora of data in the critical care setting, there are
      few studies to guide clinicians in the hospitalwide care of patients with
      hyperglycemia. METHODS: Patients 18 years of age and older who had a discharge
      diagnosis code for diabetes were admitted between January 1, 2005, and December
      31, 2010, and received an insulin infusion for any reason were included in the
      analysis. Patients were receiving noncritical care or cardiac care (with
      interchangeable critical and noncritical care capacity). The effect of an insulin
      infusion guideline introduced in 2006 with a target glucose of 5.6-8.3 mmol/L was
      measured. Hyperglycemic (> 11.1 mmol/L) and hypoglycemic (< 3.9 or < 2.8 mmol/L)
      events were analyzed using multivariable models. RESULTS: After adjusting for
      age, gender, race, and nutrition, there was a significant decrease in time to
      first glucose < 8.3 mmol/L in hours (T8.3; p = .01) and hyperglycemia (p < .0001)
      in the year following implementation of the guideline in cardiac but not
      noncritical beds, which persisted through 2010. There was a significant decrease
      in hypoglycemic events by Year 3 in cardiac beds and by Year 5 in noncritical
      beds. Compared with patients who received nothing by mouth, patients eating
      discrete meals had significantly longer T8.3, greater variability, and more
      hyperglycemic and hypoglycemic events in cardiac and noncritical beds.
      CONCLUSIONS: Following the hospitalwide implementation of a nursing-run insulin
      infusion guideline, rapid, stable reduction in hyperglycemia was achieved in
      cardiac beds (having interchangeable ICU and non-ICU status), and the frequency
      of hypoglycemia steadily decreased over time in both cardiac and noncardiac beds.
      Oral intake and enteral feeding were associated with worse glycemic control.

PMID- 24730208
TI  - Development of a Web-based surgical booking and informed consent system to reduce
      the potential for error and improve communication.
AB  - BACKGROUND: The decision to perform an elective procedure often originates during
      an office visit between surgeon and patient. Several administrative tasks follow,
      including scheduling or "booking" of the case and obtaining informed consent.
      These processes require communicating accurate information regarding diagnosis,
      procedure, and other patient-specific details necessary for the safe and
      effective performance of an operation. Nonstandardized and paper-based consents
      pose difficulty with legibility, portability, and consistency, thereby
      representing a source of potential error and inefficiency. There are numerous
      barriers to efficiently booking elective surgical procedures and obtaining a
      legible, complete, and easily retrievable informed consent. An integrated Web
      based booking and consent system was developed at a multisite university
      affiliated community hospital system to improve the speed and quality of work
      flow, as well as communication with both the patients and staff. METHODS: A
      booking and consent system was developed and made available over the intranet.
      This customized system was created by leveraging existing information systems.
      RESULTS: The electronic consent system uses surgeon-specific templates and allows
      for a consistent approach to each procedure. A printed consent form can be
      generated at any time from any of the health care system's three campuses and is
      commonly stored in the electronic medical record. Integration into our
      perioperative system allows for coordination with the operating room staff,
      administrative personal, financial coordinators, and central supply. Total
      systems expenditure for development was estimated at $40,000 (US). CONCLUSIONS:
      Organizations considering standardizing their own consent and operating room
      booking processes can review this experience in making their own "make or buy"
      decision for their own settings.

PMID- 24730209
TI  - Classification tree analysis of race-specific subgroups at risk for a central
      venous catheter-related bloodstream infection.
AB  - BACKGROUND: Studies of racial disparities in patient safety events often do not
      use race-specific risk adjustment and do not account for reciprocal covariate
      interactions. These limitations were addressed by using classification tree
      analysis separately for black patients and white patients to identify
      characteristics that segment patients who have increased risks for a venous
      catheter-related bloodstream infection. METHODS: A retrospective, cross-sectional
      analysis of 5,236,045 discharges from 103 Florida acute hospitals in 2005-2009
      was conducted. Hospitals were rank ordered on the basis of the black/white
      Patient Safety Indicator (PSI) 7 rate ratio as follows: Group 1 (white rate
      higher), Group 2, (equivalent rates), Group 3, (black rate higher), and Group 4,
      (black rate highest). Predictor variables included 26 comorbidities (Elixhauser
      Comorbidity Index) and demographic characteristics. Four separate classification
      tree analyses were completed for each race/hospital group. RESULTS: Individual
      characteristics and groups of characteristics associated with increased PSI 7
      risk differed for black and white patients. The average age for both races was
      different across the hospital groups (p < .01). Weight loss was the strongest
      single delineator and common to both races. The black subgroups with the highest
      PSI 7 risk were Medicare beneficiaries who were either < or = 25.5 years without
      hypertension or < or = 39.5 years without hypertension but with an emergency or
      trauma admission. The white subgroup with the highest PSI 7 risk consisted of
      patients < or = 45.5 years who had congestive heart failure but did not have
      either hypertension or weight loss. DISCUSSION: Identifying subgroups of patients
      at risk for a rare safety event such as PSI 7 should aid effective clinical
      decisions and efficient use of resources and help to guide patient safety
      interventions.

PMID- 24730210
TI  - What causes EBRI retirement readiness ratings to vary: results from the 2014
      Retirement Security Projection Model.
AB  - RETIREMENT INCOME ADEQUACY IMPROVED SLIGHTLY IN 2013: Due to the increase in
      financial market and housing values during 2013, the probability that Baby
      Boomers and Generation Xers would NOT run short of money in retirement increases
      between 0.5 and 1.6 percentage points, based on the Employee Benefit Research
      Institute (EBRI) Retirement Readiness Ratings (RRRs). ELIGIBILITY FOR
      PARTICIPATION IN AN EMPLOYER-SPONSORED DEFINED CONTRIBUTION PLAN REMAINS ONE OF
      THE MOST IMPORTANT FACTORS FOR RETIREMENT INCOME ADEQUACY: RRR values double for
      Gen Xers in the lowest-income quartile when comparing those with 20 or more years
      of future eligibility with those with no years of future eligibility, while those
      in the middle income quartiles experience increases in RRR values by 27.1-30.3
      percentage points. FUTURE SOCIAL SECURITY BENEFITS MAKE A HUGE DIFFERENCE FOR THE
      RETIREMENT INCOME ADEQUACY OF SOME HOUSEHOLDS, ESPECIALLY GEN XERS IN THE LOWEST
      INCOME QUARTILE: If Social Security benefits are subject to proportionate
      decreases beginning in 2033 (according to the values in Figure 8), the RRR values
      for those households will drop by more than 50 percent: from 20.9 percent to 10.3
      percent. LONGEVITY RISK AND STOCHASTIC HEALTH CARE RISK ARE ASSOCIATED WITH HUGE
      VARIATIONS IN RETIREMENT INCOME ADEQUACY: For both of these factors, a comparison
      between the most "risky" quartile with the least risky quartile shows a spread of
      approximately 30 percentage points for the lowest income range, approximately 25
      to 40 percentage points for the highest income range, and even larger spreads for
      those in the middle income ranges. A GREAT DEAL OF THE VARIABILITY IN RETIREMENT
      INCOME ADEQUACY COULD BE MITIGATED BY APPROPRIATE RISK-MANAGEMENT TECHNIQUES AT
      OR NEAR RETIREMENT AGE: For example, the annuitization of a portion of the
      defined contribution and IRA balances may substantially increase the probability
      of not running short of money in retirement. Moreover, a well-functioning market
      in long-term care insurance would appear to provide an extremely useful technique
      to help control the volatility from the stochastic, long-term health care risk,
      especially for those in the middle income quartiles.

PMID- 24730211
TI  - [Investigation of molecular virulence factors of Yersinia enterocolitica 1B/08
      human clinical isolates collected in Poland in 2009].
AB  - INTRODUCTION: The high-pathogenicity Y. enterocolitica bioserotype 1B/O8 has been
      isolated from human clinical samples since 2004 year in Poland. The group of
      "American" strains of Y. enterocolitica is considered to be the second, major
      causative agent ofyersiniosis in Poland, after the predominant bioserotype 4/O3.
      The high-pathogenicity of Y. enterocolitica 1B/O8 is likely attributed to the
      presence of a couple of chromosomally encoded virulence factors including
      yersiniabactin (Ybt). The aim of the present study was to examine the occurrence
      of known virulence factors in human clinical isolates of Yersinia enterocolitica
      bioserotype 18/08, isolated in Poland. METHODS: The group of 64 isolates of Y.
      enterocolitica bioserotype 1B/O8, isolated from clinical specimens in Poland in
      2009 year was examined for the presence of the selected virulence determinants by
      multiplex-PCR. RESULTS: All of the tested Y. enterocolitica 1B/O8 isolates have
      the same virulotype (ail+, ystA+, myfA+, myfB+, myfC+ irp1+, irp2+, fuyA+, yst1+
      chiY+, ysrS+), specific for the high--pathogenicity American strains of Y.
      enterocolitica. CONCLUSIONS: Presence of the genes encoding yersiniabactin
      (irp1+, irp2+, fuyA+), chromosomal secretion system Ysa (chiY+, ysrS+) and Yst1
      (yst1+) may argue for the extended pathogenic potential of the Y. enterocolitica
      bioserotype 1B/O8 in Poland.

PMID- 24730212
TI  - [Electrophoretic and immunological analysis of native proteins secreted in vitro
      under conditions inducing Ysa (Yersinia secretion apparatus) by clinical isolates
      of Yersinia enterocolitica 1B/O8 in Poland].
AB  - INTRODUCTION: The high pathogenicity Yersinia enterocolitica 1B/O8 produce
      variety of virulence factors including chromosomal T3SS known as Ysa-Ysp system
      that is considered to act at the early stage of infection. The aim of the study
      was to examine the ability to produce Ysa-Ysp proteins in vitro by human clinical
      isolates of the epidemic Y. enterocolitica 1B/O8 strains in native conditions and
      immunological characterization of expressed proteins. METHODS: Seven Y.
      enterocolitica 1B/O8 isolates with known epidemiological link and the reference
      high pathogenicity strain WA-314 and six strains from the Institute Pasteur
      (France) were examined for production of Ysa-Ysp proteins according with
      procedure described by Matsumoto and Young (Mol. Microbiol., 2006, 59:689-76).
      All the isolates and strains were characterized by SDS-PAGE to determined Ysa-Ysp
      proteins profile. The immunological characterization was performed by using
      western-immunobloting method using sera from two immunized rabbits and from two
      patients with bacteriology confirmed Y. enterocolitica 1B/O8 infection. RESULTS:
      The reference strain WA-314 yielded typical Ysa-Ysp proteins profile. In contrast
      all the tested Y. enterocolitica 1B/O8 human isolates yielded the same SDS--PAGE
      profile that was apparently distinct from profile of Ysa-Ysp proteins of
      reference strain WA-314. CONCLUSIONS: The Y. enterocolitica 1B/O8 isolates of the
      epidemic strain circulating in Poland were found to be unable to produce Ysa-Ysp
      proteins in vitro under conditions sufficient to stimulate expression of the Ysa
      Ysp proteins in the reference strain WA-314 and strains from the Institute
      Pasteur (France). Our results may suggest that the ability to produce Ysa--Ysp
      proteins in concentrations sufficient to induce production of specific antibodies
      is not indispensible for Y. enterocolitica 1B/O8 infection in humans. The western
      immunoblotting analysis of human serum samples showed that the antibodies were
      not induced by Ysa and Ysp proteins during infection caused by the epidemic
      strain of Y. enterocolitica 1B/O8 circulating in Poland. Similar, negative result
      was found with serum of a rabbit immunized intravenously by the reference strain
      WA-314. The project was funded by the National Science Centre in Cracov, Poland,
      grant N N401 076039.

PMID- 24730213
TI  - [Comparison of usefulness of commercial ELISA Virion/Serion, homemade ELISA and
      tube agglutination test in serodiagnosis of tularemia].
AB  - INTRODUCTION: Tularemia is a highly infectious zoonotic disease caused by Gram
      negative bacterium Francisella tularensis. The microbiological diagnosis of
      tularemia is based on bacteriological, molecular and serological investigations.
      In the present study we compared of usefulness of commercial ELISA Virion/Serion,
      home-made ELISA and tube agglutination test in serodiagnosis of tularemia.
      METHODS: Serum samples from 57 patients with clinical symptoms of tularemia, 13
      patients with yersiniosis and 20 blood donors were tested. The cut-off limit of
      IgA, IgG and IgM serum antibodies in home-made ELISA was set at mean antibody
      titer determined in sera of healthy blood donors exceeded by the three standard
      deviations. The cut-off for positivity in tube agglutination test was titers 25.
      The IgG and IgM antibodies to lipopolysaccharides of F. tularensis in
      Virion/Serion ELISA were measured and results interpreted according to the
      instructions by the manufacturer. RESULTS: The results of the study showed that
      39 (68.4%) serum samples obtained from the patients suspected for tularemia were
      positive by tube agglutination test and Virion/Serion ELISA assay for IgG and IgM
      antibodies. Home-made ELISA was slightly more sensitive and detected the IgA/IgG
      antibodies in 42 (73.7%) and IgM antibodies in 39 (68.4%) of serum samples. The
      positive reactions were not detected by the tube agglutination test and home-made
      ELISA in serum samples from patients with yersiniosis and blood donors. The
      Virion/Serion ELISA detected IgG antibodies in diagnostically significant level
      only in one blood donor. CONCLUSIONS: In conclusion, all three serological tests
      can be successfully used in routine serodiagnosis of tularemia.

PMID- 24730214
TI  - [The use of two-stage algorithm in the diagnosis of patients with low levels of
      Clostridium difficile toxins A/B in feces confirmed by using enzyme immunoassay].
AB  - INTRODUCTION: Clostridium difficile infection (CDI) is a serious problem in
      hospitalized patients. Rapid and accurate laboratory diagnosis is the key to
      reducing of CDI. The suboptimal sensitivity and specificity of many commercial
      enzyme immunoassays have limited their utility. The aim of this study was
      analysis of faecal samples obtained from patients with clinical evidence of CDI,
      with non-detectable or questionable result of toxins A/B C. difficile recognized
      by toxins A/B EIA test. METHODS: A two-step algorithm for diagnostics of C.
      difficile infection (CDI) in patients with non-detectable or questionable result
      of toxins A/B C. difficile confirmed by C. difficile enzyme immunoassay (EIA)
      (Wampole, TOX A/B II, TechLab, USA) was used. Sixty nine faecal samples obtained
      from patients with nosocomial diarrhea were retested. All faecal samples were
      cultured on selective medium CLO C. difficile (BioMerieux, Francja). The positive
      samples on selective medium were tested by using Real Time-PCR (Xpert CD assay,
      Cepheid, Sunnyvale, CA, USA). Xpert CD assay is a real time multiplex PCR that
      can be used to detect toxigenic C. difficile strains and differentiate the C.
      difficile presumptive NAP1/BI/027 strain. All results when faecal samples were
      negative in culture growth on selective medium and result of EIA test were
      questionable was confirmed by use a RT-PCR test. RESULTS: Among 69 faecal samples
      56 were negative for toxins A/B using EIA test and 13 gave questionable results.
      By anaerobic culture 60 of 69 specimens yielded C. difficile isolates. Among 69
      faecal samples 55 were positive using RT-PCR. Thirty four (62%) of patients was
      infected by presumptive C. difficile NAP1/BI/027. CONCLUSIONS: C. difficile
      testing by use of culture and Real Time PCR (RT-PCR) increases diagnostic yield
      in a hospital patients with non-detectable or low level of toxins A/B in stool
      samples of patients infected by toxigenic C. difficile strains including
      presumptive C. difficile NAP1/BI/027.

PMID- 24730215
TI  - [Serum immunoglobulin IgG subclass distribution of antibody responses to
      pertussis toxin and filamentous hemagglutinin of Bordetella pertussis in patients
      with whooping cough].
AB  - INTRODUCTION: The present study was aimed at determining the IgG subclass
      distribution against pertussis toxin (PT) and filamentous hemagglutinin (FHA) of
      Bordetella pertussis in patients with whooping cough. METHODS: The total number
      of 222 serum samples obtained from patients suspected in clinical investigation
      for pertussis were tested separately by in-house ELISA for the presence of IgG
      antibodies to pertussis toxin and filamentous hemagglutinin. The percentage
      distribution of specific anti-PT and anti-FHA IgG subclass response was
      calculated only on the basis of group of sera confirmed in the present study as
      positive for total IgG antibodies (183 sera to PT antigen and 129 to FHA
      antigen). Paired serum specimens were obtained from 36 patients. Based on the
      results of determining the level of antibodies in the sera of 40 blood donors,
      the cut-off limit of serum antibodies for each subclass was set at arithmetic
      mean plus two standard deviations. RESULTS: Antibodies of IgG1 to pertussis toxin
      and filamentous hemagglutinin were diagnosed in 151 (82.5%) and 99 (76.7%), IgG2
      in 72 (39.0%) and 50 (38.8%), IgG3 in 17 (9.3%) and 43 (33.3%), IgG4 in 55
      (30.1%) and 53 (41.1%) serum samples, respectively. There were no significant
      differences in percentage of sera with IgG1, IgG2 and IgG3 in relation to age of
      the patients. However, the frequency of occurrence of IgG4 antibodies was highest
      in the group of the youngest children to the age of 6 years old (61.8% for PT and
      68.0% for FHA), and decrease with age, reaching the minimum in the group of
      patients above 40 years old (13.2% and 4.2% for PT and FHA, respectively). We
      also found significantly higher frequency of IgG4 to PT and FHA antigens in men
      than in women. Statistically significant, essential changes in the pattern of IgG
      subclass during the course of infection were not found. CONCLUSIONS: In
      conclusion, this study showed that all four subclasses of IgG antibodies to
      pertussis toxin and filamentous hemagglutinin are produced during whooping cough.

PMID- 24730216
TI  - [Methods of testing potential inhibitors of hepatitis C in Huh-7.5 cell line].
AB  - INTRODUCTION: According to WHO reports, there are 130-170 million persons
      chronically infected with hepatitis C virus on a global scale. There is no
      effective vaccine against HCV, and the current standard of chronic hepatitis C
      therapy has limited efficiency and undesirable side effects. Current studies are
      focused on searching for a new therapeutic agents, which are specifically
      targeted against the virus. The aim of the study was to develop a methodology for
      testing the activity and cytotoxicity of potential helicase inhibitors
      (derivatives of anthracycline antibiotics) in Huh-7.5 cell line infected with
      HCV. METHODS: The Huh-7.5 cell line was infected with the JFH1 (Japanese
      Fulminant Hepatitis) RNA by lipofection. The cytotoxicity of anthracycline
      antibiotics was measured by Cell Proliferation Kit II(XTT), after 1, 2, 3, 4 and
      24 hours after incubation with tetrazolium salt XTT. The activity ofanthracycline
      antibiotics was examined by Real-Time PCR method. RESULTS: The study allowed to
      optimize the conditions of cytotoxicity and activity studies of anthracycline
      antibiotics. CONCLUSIONS: Huh-7.5 cell line infected with HCV is a robust cell
      culture model for screening new antivirals against HCV.

PMID- 24730217
TI  - [Characteristics of Clostridium tetani and laboratory diagnosis of tetanus].
AB  - The causative agent of tetanus is the obligate anaerobic bacterium--Clostridium
      tetani. These bacteria form endospores that are able to survive long periods of
      exposure to air and other adverse environmental conditions. Infection generally
      occurs through wound contamination. We can distinguish several forms of tetanus:
      generalized, local and neonatal. Diagnosis of tetanus is based primarily on the
      patient's clinical symptoms (muscle cramps, painful back muscle spasms,
      generalized contractions of the arcuate curvature of the body) as well as on
      microbiological diagnosis. This article is a brief review of C. tetani and
      diagnosis of infections caused by these organisms in humans.

PMID- 24730218
TI  - A bitter winter's tale.

PMID- 24730219
TI  - Survey shows growing approval and acceptance of integrated, employed physicians.
AB  - Hundreds of physician leaders share their insights and opinions on the integrated
      employed physician models that are quickly rising up throughout the country.

PMID- 24730220
TI  - Do integrated health care systems provide lower-cost, higher-quality care?
AB  - A study Looking at quality and cost issues for integrated vs. non integrated
      physician practices yields some interesting findings.

PMID- 24730221
TI  - Physician/Congressman takes on Medicare reimbursement.
AB  - Michael Burgess, MD, is lead sponsor of a bill to replace the much maligned
      Sustained Growth Formula that is used to determine Medicare reimbursements.

PMID- 24730222
TI  - Physician self-assessment of leadership skills.

PMID- 24730223
TI  - Cutting costs while maintaining quality: how the VA has leveraged simulation.
AB  - Simulation training in the Department of Veterans Affairs has saved money and
      improved outcomes and is now being used throughout the organization.

PMID- 24730224
TI  - Physician recruitment and retention: a physician's perspective.
AB  - In order to overcome the inevitable physician shortage, physician groups and
      hospitals must acknowledge and incorporate effective recruiting techniques into
      their practices.

PMID- 24730225
TI  - Execution by Swarm: managing via constraint in and adaptive health care
      environment.
AB  - Find out how the swarm theory can be applied to finding ways to provide high
      quality patient-centered care, even in the chaos that surrounds care delivery in
      many health care organizations.

PMID- 24730226
TI  - Cox on communications.

PMID- 24730227
TI  - Organizational insight for physician leaders: a critical perspective.
AB  - Learn how to develop and institute the organizational awareness that leadership
      teams require to run healthy medical care systems.

PMID- 24730228
TI  - Sea squirts and organizational excellence.
AB  - What is a sea squirt and what in heck does it have to do with the day-to-day
      challenges of achieving and sustaining organizational excellence?

PMID- 24730229
TI  - Mental health parity: where it has been and where it's going. it.

PMID- 24730230
TI  - Affordable Care Act: lifting the curtain on health care cost.

PMID- 24730231
TI  - Can physician leaders learn to think like systems engineers? k.

PMID- 24730232
TI  - The role of mentoring.

PMID- 24730233
TI  - Advances in stimuli responsive nanobiomaterials for cancer therapy.
AB  - Cancer has become one of the major reasons for disease mortality with drastic
      increase of death rate in recent years. The reason for most of these deaths is
      due to the inefficacy and failure of the current methods of treatments or due to
      the unavailability of treatment options. Even after extensive research that has
      been carried out in the field, there is no gold standard in cancer therapy. With
      the advancement of the field of nanomedicine and materials science, many research
      works are being aimed at developing micro and nanocarriers for site-specific
      delivery of anticancer drugs. As a further advancement in the field, smart
      carriers, based on nanobiomaterials, which respond to various external and
      internal stimuli and act locally are being developed to improve the efficacy of
      current treatments. These smart nanobiomaterials act as carriers for not only
      anticancer drugs but also for gene and other biomolecules. Keeping the importance
      and advancement of smart carrier anticancer drug delivery system (AcDDS) in view,
      this review focuses on stimuli responsive nanobiomaterials that are currently
      being studied for cancer therapy.

PMID- 24730234
TI  - Gold nanoparticle based X-ray contrast agent for tumor imaging in mice and dog: a
      potential nano-platform for computer tomography theranostics.
AB  - The goal of our study was to demonstrate the utility of nanocrystalline gold as
      an X-ray contrast agent for imaging tumor in living subjects. Even though
      significant progress has been achieved in this area by researchers, clinical
      translation remains challenging. Here, we investigated biocompatible gum Arabic
      stabilized gold nanocrystals (GA-AuNPs) as X-ray contrast agent in tumor bearing
      mice and dog. Single intratumoral injections of GA-AuNP resulted in X-ray
      contrast change of -26 HU in the tumor region after 1 hour post-injection period.
      Subsequently, five intratumoral injections were performed in the mice. The change
      in CT number in tumor region is not progressive; rather it reaches a saturation
      point after fourth injection. These data suggested that accumulation of GA-AuNP
      reaches a threshold limit within a short time period (5 h), and is retained in
      the tumor tissue for the rest of the period of investigation. A pilot study was
      conducted in a client-owned dog presented with collision tumor of thyroid
      carcinoma and osteosarcoma. In this study, GA-AuNP was injected intratumorally in
      dog and a contrast enhancement of 12 deltaHU was observed. The CT images of both
      mice and dog clearly demonstrated that GA-AuNP was effectively distributed and
      retained throughout the tumor site. The CT data obtained by the present study
      would provide the crucial dosimetry information for strategic therapy planning
      using this construct. Both mice and dog did not show any clinical changes,
      thereby confirming that GA-AuNP did not induce toxicity and can be explored for
      future clinical applications.

PMID- 24730235
TI  - Molecular targeting radiotherapy with cyclo-RGDFK(C) peptides conjugated to 177Lu
      labeled gold nanoparticles in tumor-bearing mice.
AB  - Peptides based on the cyclic Arg-Gly-Asp (RGD) sequence have been designed to
      antagonize the function of alpha(v)beta(3) integrin, thereby inhibiting
      angiogenesis. The conjugation of RGD peptides to radiolabeled gold nanoparticles
      (AuNP) produces biocompatible and stable multimeric systems with target-specific
      molecular recognition. The aim of this research was to evaluate the therapeutic
      response of 177Lu-AuNP-RGD in athymic mice bearing alpha(v)beta(3)-integrin
      positive C6 gliomas and compare it with that of 177Lu-AuNP or 177Lu-RGD. The
      radiation absorbed dose, metabolic activity (SUV, [18F]fluor-deoxy-glucose
      microPET/CT), histological characteristics and VEGF gene expression (by real-time
      polymerase chain reaction) in tumor tissues following treatment with 177Lu-AuNP
      RGD, 177Lu-AuNP or 177Lu-RGD were assessed. Of the radiopharmaceuticals
      evaluated, 1177Lu-AuNP-RGD delivered the highest tumor radiation absorbed dose
      (63.8 +/- 7.9 Gy). These results correlated with the observed therapeutic
      response, in which 177Lu-AuNP-RGD significantly (p < 0.05) induced less tumor
      progression, less tumor metabolic activity, fewer intratumoral vessels and less
      VEGF gene expression than the other radiopharmaceuticals, a consequence of high
      tumor retention and a combination of molecular targeting therapy (multimeric RGD
      system) and radiotherapy (177Lu). There was a low uptake in non-target organs and
      no induction of renal toxicity. 177Lu-labeled gold nanoparticles conjugated to
      cyclo-RGDfK(C) demonstrate properties suitable for use as an agent for molecular
      targeting radiotherapy.

PMID- 24730236
TI  - Anomalous subsurface thermal behavior in tissue mimics upon near infrared
      irradiation mediated photothermal therapy.
AB  - Photothermal therapy using (Near Infrared) NIR region of EM spectrum is a fast
      emerging technology for cancer therapy. Different types of nanoparticles may be
      used for enhancing the treatment. Though the treatment protocols are developed
      based on experience driven estimated temperature increase in the tissue, it is
      not really known what spatiotemporal thermal behavior in the tissue is. In this
      work, this thermal behavior of tissue models is investigated with and without
      using nanoparticles. An increased temperature inside tissue compared to surface
      is observed which is counter intuitive from the present state of knowledge. It is
      shown from fiber level microstructure that this increased temperature leads to
      enhanced damage at the deeper parts of biomaterials. Nanoparticles can be
      utilized to control this temperature increase spatially. A multiple scattering
      based physical model is proposed to explain this counterintuitive temperature
      rise inside tissue. The results show promising future for better understanding
      and standardizing the protocols for photothermal therapy.

PMID- 24730237
TI  - Novel L-lactide-depsipeptide polymeric carrier for enhanced brain uptake of
      rivastigmine in treatment of Alzheimer's disease.
AB  - The present study discusses possibility of targeting an anti-Alzheimer's drug
      rivastigmine tartarate (RT) to the brain using novel synthesized L-lactide
      depsipeptide polymeric nanoparticles (NPs). Single emulsion-solvent evaporation
      technique was used for preparation of NPs. The mean particle size, zeta potential
      and entrapment efficiency of drug loaded NPs were found to be 142.2 +/- 21.3 nm,
      +4.85 mV and 60.72 +/- 3.72% respectively. Pharmacodynamic study showed faster
      regain of memory loss in amnesic rat with RT loaded NPs as compared to RT
      solution. In pharmacokinetic study, total concentration and mean residence time
      was increased up to 3.79 fold and 2 fold respectively while clearance was
      decreased to 1.91 fold on intravenous administration of RT loaded NPs as compared
      to RT solution. The biodistribution study demonstrated 5.45 fold and 2 fold
      increase in brain concentration of drug after administration of RT loaded NPs
      (i.v; 10.52 +/- 1.31 ng/ml) as compared to plain RT solution by oral (1.93 +/-
      1.23 ng/ml) and intravenous (5.34 +/- 1.22 ng/ml) route, respectively. Therefore,
      RT loaded L-lactide-depsipeptide polymeric NPs might be a potential drug delivery
      system in treatment of Alzheimer's disease.

PMID- 24730238
TI  - Biodegradable and thermosensitive monomethoxy poly(ethylene glycol)-poly(lactic
      acid) hydrogel as a barrier for prevention of post-operative abdominal adhesion.
AB  - Post-operative peritoneal adhesions are serious consequences of abdominal or
      pelvic surgery and cause severe bowel obstruction, chronic pelvic pain and
      infertility. In this study, a novel nano-hydrogel system based on a monomethoxy
      poly(ethylene glycol)-poly(lactic acid) (MPEG-PLA) di-block copolymer was studied
      for its ability to prevent abdominal adhesion in rats. The MPEG-PLA hydrogel at a
      concentration of 40% (w/v) was injected and was able to adhere to defect sites at
      body temperature. The ability of the hydrogel to inhibit adhesion of post
      operative tissues was evaluated by utilizing a rat model of abdominal sidewall
      cecum abrasion. It was possible to heal wounded tissue through regeneration of
      neo-peritoneal tissues ten days after surgery. Our data showed that this hydrogel
      system is equally as effective as current commercialized anti-adhesive products.

PMID- 24730239
TI  - siRNA delivery mediated by copolymer nanoparticles, phospholipid stabilized
      sulphur hexafluoride microbubbles and ultrasound.
AB  - The combination of ultrasound (US) and microbubbles (MB) is a promising physical
      method for improving the nanoparticles (NPs) delivery efficiency. However, few
      concerns over comparable delivery effect of the passive or active targeting
      property's NPs mediated by US and MB have limited their translation towards
      further application. For this, we prepared small interfering RNA (siRNA)-loaded
      mPEG-PLGA-PLL (siRNA/mPPP) NPs with passive targeting property and siRNA-loaded
      mPEG-PLGA-PLL-cRGD (siRNA/mPPPR) NPs with active targeting property, and
      evaluated the effect of US and MB for their delivery efficiency. The experimental
      results demonstrated that US and MB effectively enhance the siRNA delivery
      efficiency of the mPPP NPs compared with the mPPP NPs alone. In contrast, an
      improved delivery efficiency of siRNA was not observed in PC-3 cells treated with
      the mPPPR NPs mediated by US and MB, suggesting that the delivery efficiency of
      NPs mediated US and MB also depend on its targeting properties.

PMID- 24730240
TI  - Doxorubicin-loaded cyclic peptide nanotube bundles overcome chemoresistance in
      breast cancer cells.
AB  - The purpose of this study was to design and fabricate a new cyclic peptide-based
      nanotube (CPNT) and to explore its potential application in cancer therapy. For
      such a purpose, the CPNT bundles with a diameter of -10 nm and a length of -50-80
      nm, self-assembled in a micro-scaled aggregate, were first prepared using a
      glutamic acid and a cysteine residue-containing cyclic octapeptide. In order to
      explore the potential application of these supramolecular structures, the CPNTs
      were loaded with doxorubicin (DOX), and further modified using polyethylene
      glycol (PEG). The PEG-modified DOX-loaded CPNTs, showing high drug encapsulation
      ratio, were nano-scaled dispersions with a diameter of -50 nm and a length of 
      200-300 nm. More importantly, compared to free DOX, the PEG-modified DOX-loaded
      CPNT bundles demonstrated higher cytotoxicity, increased DOX uptake and altered
      intracellular distribution of DOX in human breast cancer MCF-7/ADR cells in
      vitro. In addition, an enhanced inhibition of P-gp activity was observed in MCF
      7/ADR cells by the PEG-modified DOX-loaded CPNT bundles, which shows their
      potential to overcome the multidrug resistance in tumor therapy. These findings
      indicate that using cyclic peptide-based supramolecular structures as
      nanocarriers is a feasible and a potential solution for drug delivery to
      resistant tumor cells.

PMID- 24730241
TI  - The inhibitory and apoptotic effects of docetaxel-loaded mesoporous magnetic
      colloidal nanocrystal clusters on bladder cancer T24 cells in vitro.
AB  - Mesoporous magnetic colloidal nanocrystal clusters (MCNCs) are featured with high
      magnetization, adequate surface area, excellent colloidal stability, good
      biocompatibility, and acid degradability. It is thus highly anticipated that
      MCNCs can serve as vehicles for target drug delivery. Herein, the mesoporous
      MCNCs stabilized by poly(gamma-glutamic acid) (PGA) were fabricated by the
      modified solvothermal route, showing a high specific surface area (126.4 m2/g),
      strong magnetic response (63 emu/g) and appropriate mesoporosity including a
      large pore volume (0.27 cm3/g) and accessible pore size (8.1 nm). Docetaxel (DOC)
      was then loaded in the resultant MCNCs using the nanoprecipitation method, and a
      high drug loading capacity was achieved up to 24 wt%. The chemotherapeutic effect
      and mechanism of DOC-MCNC conjugates in bladder cancer was evaluated in vitro. A
      series of analyses for cell uptake, cell viability, cell cycle, cell apoptosis
      and some cell proteins were performed by transmission electron microscopy, MTT
      assay, flow cytometry, cell nuclei staining, Annexin V staining assay, western
      blot assay and caspase-3 activity assay, respectively. The results demonstrated
      that DOC-MCNC conjugates enhanced the inhibitory effect by hampering mitoschisis
      and increased the apoptotic effect by changing the expression of apoptosis
      related proteins in T24 cells, substantially proving their remarkable efficiency
      in treatment of bladder cancer.

PMID- 24730242
TI  - Carbon nanofibers and carbon nanotubes sensitize prostate and bladder cancer
      cells to platinum-based chemotherapeutics.
AB  - Recent data suggest that carbon nanomaterials can act as antitumor agents
      themselves by increasing the efficiency of cytotoxic agents when applied in
      combination. Here, carbon nanofibers (CNFs) and multi-walled carbon nanotubes
      (CNTs) were investigated regarding their impact on cellular function, cellular
      uptake and ability to sensitize cancer cells of urological origin to the
      conventional chemotherapeutics cisplatin and carboplatin. CNFs and CNTs (1-200
      microg/ml) showed a low to moderate impairment of cellular function with CNFs
      being more deleterious than CNTs. Inhibition of cellular viability by the
      nanomaterials was about 20% at most. In combinatory treatments, CNFs and CNTs
      markedly enhanced the effects of cisplatin and carboplatin on cellular viability
      by 1.2- to 2.8-fold in prostate, bladder and cisplatin-resistant prostate cancer
      cells in comparison to the individual effects of the chemotherapeutics.
      Particularly the cell viability-diminishing effect of CNFs alone and in
      combination with the chemotherapeutics was more pronounced with dispersions
      prepared with human serum albumin than with phospholipid-polyethylene glycol.
      Albumin might mediate the cellular uptake of carbon nanomaterials which was
      underlined by the co-localization of albumin and carbon nanomaterials along the
      cellular surface as evidenced by fluorescence microscopy. Transmission electron
      microscopy revealed that both carbon nanomaterials were internalized by cancer
      cells, thereby possibly leading to an enhanced accumulation of the
      chemotherapeutic drugs. In fact, CNFs enhanced the cellular accumulation of
      carboplatin by 28% as compared to the single treatment with carboplatin. In
      conclusion, carbon nanomaterial-based applications could present a new strategy
      to overcome chemoresistance by sensitizing cancer cells to conventional
      chemotherapeutics.

PMID- 24730243
TI  - Label-free detection of blood plasma using silver nanoparticle based surface
      enhanced Raman spectroscopy for esophageal cancer screening.
AB  - A surface-enhanced Raman spectroscopy (SERS) based on silver nanoparticle
      technology was applied to analyze and classify human blood plasma with the aim to
      develop a simple and label-free blood test for esophageal cancer detection. High
      quality SERS spectra in the range of 400-1800 cm(-1) can be acquired from 36
      esophageal cancer patients and 50 healthy volunteers' blood plasma samples.
      Tentative assignments of the SERS bands indicated specific biomolecular changes
      associated with cancer transformation, including an increase in the relative
      amounts of nucleic acid and phenylalanine, a decrease in the percentage of
      saccharide and proteins contents in the cancer blood plasma compared to that of
      healthy subjects. Furthermore, both SVM and PCA-LDA diagnostic algorithm were
      employed to analyze and classify the obtained blood plasma SERS spectra between
      normal and cancer plasma with a high diagnostic accuracy (around 90%). This
      exploratory work demonstrates that the label-free plasma SERS analysis technique
      in conjunction with SVM and PCA-LDA diagnostic algorithms has great potential for
      improving esophageal cancer detection and screening.

PMID- 24730244
TI  - Nanofibrous mats layer-by-layer assembled by HTCC/layered silicate composites
      with in vitro antitumor activity against SMMC-7721 cells.
AB  - Organic rectorite (OREC) was used to prepare the intercalated nanocomposites with
      N-(2-hydroxyl) propyl-3-trimethyl ammonium chitosan chloride (HTCC), and then the
      immobilization of the positively charged HTCC-OREC nanocomposites and the
      negatively charged sodium alginate (ALG) on cellulose nanofibrous mats was
      performed through layer-by-layer (LBL) technique. Fiber diameter distribution
      results from Field Emission Scanning Electron Microscopy (FE-SEM) images showed
      that the average fiber diameter of (HTCC-OREC/ALG)(n) films coating obviously
      increased from 433 to 608 nm. Moreover, X-ray photoelectron spectroscopy (XPS)
      and X-ray diffraction (XRD) results further confirmed the interaction between
      HTCC and OREC and their successful immobilization on cellulose template. MTT
      assay indicated that the prepared nanofibrous mats exhibited strong inhibitory
      activity against human hepatocellular carcinoma cells (SMMC-7721) but a little
      cytotoxic effect on human Chang liver (CCL-13) cells. Furthermore, the
      experimental results from FE-SEM and Inverted Fluorescence Microscope of SMMC
      7721 cells cultured on LBL structured nanofibrous mats demonstrated the
      significant antitumor activity of prepared samples. The developed approach to
      immobilize nanocomposites onto polymer nanofibers with controllable thickness may
      also be utilized to tumor therapy.

PMID- 24730245
TI  - Development and characterization of lactoferrin loaded poly(epsilon-caprolactone)
      nanofibers.
AB  - Lactoferrin loaded poly (epsilon-caprolactone) nanofibers were fabricated using
      the process of electrospinning and the osteocompatibility of the scaffolds were
      evaluated using MC3T3-E1 osteoblast-like cells. Morphology of rhLF/PCL scaffolds
      was determined by scanning electron microscopy. Fourier transform infrared
      spectroscopy and Energy-dispersive X-ray spectroscopy confirmed the incorporation
      of rhLF in the PCL nanofibers. The surface distribution of rhLF on the nanofibers
      was evaluated using fluorescently tagged (Far-red) rhLF. The presence of rhLF on
      rhLF/PCL nanofibers significantly increased the proliferation and viability of
      MC3T3-E1 cells compared to cells seeded on PCL nanofibers as evidenced from Ki67
      immuno-staining and MTT assay. The study demonstrated the feasibility of
      incorporating different concentrations of rhLF in PCL nanofibers and the
      potential of the fiber matrix to support osteoblast cell functions.

PMID- 24730246
TI  - Evaluation of in vitro macrophage response and in vivo host response to growth
      factors incorporated chitosan nanoparticle impregnated collagen-chitosan
      scaffold.
AB  - The purpose of this study was to evaluate the in vitro macrophage compatibility,
      the inflammatory response and in vivo host response to a novel collagen-chitosan
      (COL-CS) scaffold containing growth factors incorporated Chitosan Nanoparticle
      (CNP). The scaffold was obtained by freezing a blend of COL-CS solution and
      growth factor incorporated CNP followed by lyophilization. High Resolution
      Transmission Electron Micrograph (HR-TEM) indicated that growth factors
      incorporated CNP were in the size range of 50-100 nm, while Scanning Electron
      Microscopic (SEM) analysis of the scaffold surface suggests that the pores of the
      scaffolds (COL-CS) were well interconnected, with a mean diameter of 75-150
      microm. Macrophages grown on growth factors containing scaffold exhibited poor
      inflammatory response compared to scaffold without growth factors. In vivo
      biocompatibility and host response study of scaffold was performed by
      subcutaneous implantation and examination of the implanted material on day 3 and
      15 post implant. The dual growth factors viz. EGF (Epidermal Growth Factor) and
      FGF (Fibroblast Growth Factor) incorporated implant showed a distinct fibrous
      capsule boundary on the surface. Secondly, the immunofluoresence assay and
      zymography respectively for TNFalpha and MMP9 exhibited low expression of these
      inflammatory markers. These observations divulge that the growth factors when
      incorporated, can suppress the inflammatory properties of the scaffolds and thus
      such scaffolds could be used in tissue engineering for minimal host response and
      enhanced tissue-scaffold interaction.

PMID- 24730247
TI  - Effect of lipid coating on the interaction between silica nanoparticles and
      membranes.
AB  - Lipid coating is a method highly used to improve the biocompatibility of
      nanoparticles (NPs), even though its effect on the NP properties is still object
      of investigation. Herein, silica NPs containing methylene blue, which is a
      photosensitizer used in a variety of biomedical applications, were coated with a
      phospholipid bilayer. Regarding the photophysical properties, lipid-coating did
      not cause significant changes since bare and lipid-coated NPs presented very
      similar absorption spectra and generated singlet oxygen with similar
      efficiencies. However, NP interaction with cells and membrane mimics was totally
      different for bare and lipid-coated NPs. Lipid-coated NPs were distributed
      through the cell cytoplasm whereas bare NPs were detected only in some vacuolar
      regions within the cells. Since cellular uptake and cytolocalization are
      influenced by NP adsorption on cell membranes, the interaction of lipid-coated
      and bare NPs were studied on a membrane mimic, i.e., Hybrid Bilayer Membranes
      (HBMs) made of different compositions of negatively charged and neutral lipids.
      Interactions of bare and lipid-coated NPs with HBMs were analyzed by Surface
      Plasmon Resonance Imaging. Bare NPs presented high adsorption and aggregation on
      HBMs independently of the surface charge. Conversely, lipid-coated NPs presented
      less aggregation on the membrane surface and the adsorption was dependent on the
      charges of the NPs and of the HBMs. Our results indicated that NPs aggregation on
      the membrane surface can be modulated by lipid coating, which affects the
      cytosolic distribution of the NPs.

PMID- 24730248
TI  - Single-walled carbon nanotubes (SWCNTs) enhance KCl-, acetylcholine-, and
      serotonin-induced contractions and evoke oxidative stress on rabbit ileum.
AB  - We examined the effects of intravenous administration of purified arc-discharge
      single-walled carbon nanotubes (SWCNTs) on rabbit ileum to establish the
      possibility of using these SWCNTs as cell markers or drug carriers for the
      treatment of intestinal diseases. The SWCNT purification process eliminated
      carbonaceous impurities and decreased the amount of metals. SWCNTs increased the
      contractile responses induced by KCl, acetylcholine (ACh), and serotonin (5-HT)
      in rabbit ileum. Verapamil, apamin, glibenclamide, quinine and charybdotoxin
      reduced the contractile responses induced by ACh and 5-HT in ileum from rabbits
      treated with SWCNTs, indicating that voltage-dependent Ca2+ channels and small,
      intermediate, and large-conductance Ca(2+)-activated, ATP-sensitive, and voltage
      dependent K+ channels are involved in these effects. Atropine and hexamethonium
      reduced the ACh response, indicating that muscarinic and nicotinic receptors are
      involved in this effect. Ondansetron and GR 113808 reduced the 5-HT response,
      indicating that serotonin 5-HT3 and 5-HT4 receptors are involved in this effect.
      SWCNTs increased the malondialdehyde plus 4-hydroxyalkenals and carbonyl levels
      in rabbit plasma and ileum, indicating that SWCNTs produce oxidative stress.
      SWCNTs did not produce relevant histological changes or modify the levels of the
      inflammatory mediators iNOS and COX-2 in the ileum. In conclusion, this study
      demonstrates that the intravenous administration of SWCNTs can evoke oxidative
      stress and affect contractility in rabbit ileum. These effects could reduce the
      possibility of using the arc-discharge SWCNTs as cell markers or drug carriers to
      treat intestinal diseases.

PMID- 24730249
TI  - The nano man from India: in celebration of the 60th birthday of Dr. Hari Singh
      Nalwa.
AB  - This article is devoted to the 60th birthday of Dr. Hari Singh Nalwa and outlines
      his outstanding contributions, distinguished scientific career and business
      accomplishments to date. The January and February 2014 issues of the Journal of
      Nanoscience and Nanotechnology, dedicated to Dr. Hari Singh Nalwa on the occasion
      of his 60th birthday, provide its readers 134 state-of-the-art review articles
      contributed by leading experts from around the world focusing on a wide range of
      nanotechnology-related research areas.

PMID- 24730251
TI  - Single-cell manipulation and DNA delivery technology using atomic force
      microscopy and nanoneedle.
AB  - The recent single-cell manipulation technology using atomic force microscopy
      (AFM) not only allows high-resolution visualization and probing of biomolecules
      and cells but also provides spatial and temporal access to the interior of living
      cells via the nanoneedle technology. Here we review the development and
      application of single-cell manipulations and the DNA delivery technology using a
      nanoneedle. We briefly describe various DNA delivery methods and discuss their
      advantages and disadvantages. Fabrication of the nanoneedle, visualization of
      nanoneedle insertion into living cells, DNA modification on the nanoneedle
      surface, and the invasiveness of nanoneedle insertion into living cells are
      described. Different methods of DNA delivery into a living cell, such as
      lipofection, microinjection, and nanoneedles, are then compared. Finally, single
      cell diagnostics using the nanoneedle and the perspectives of the nanoneedle
      technology are outlined. The nanoneedle-based DNA delivery technology provides
      new opportunities for efficient and specific introduction of DNA and other
      biomolecules into precious living cells with a high spatial resolution within a
      desired time frame. This technology has the potential to be applied for many
      basic cellular studies and for clinical studies such as single-cell diagnostics.

PMID- 24730252
TI  - Medical applications of atomic force microscopy and Raman spectroscopy.
AB  - This paper reviews the recent research and application of atomic force microscopy
      (AFM) and Raman spectroscopy techniques, which are considered the multi
      functional and powerful toolkits for probing the nanostructural, biomechanical
      and physicochemical properties of biomedical samples in medical science. We
      introduce briefly the basic principles of AFM and Raman spectroscopy, followed by
      diagnostic assessments of some selected diseases in biomedical applications using
      them, including mitochondria isolated from normal and ischemic hearts, hair
      fibers, individual cells, and human cortical bone. Finally, AFM and Raman
      spectroscopy applications to investigate the effects of pharmacotherapy, surgery,
      and medical device therapy in various medicines from cells to soft and hard
      tissues are discussed, including pharmacotherapy--paclitaxel on Ishikawa and HeLa
      cells, telmisartan on angiotensin II, mitomycin C on strabismus surgery and eye
      whitening surgery, and fluoride on primary teeth--and medical device therapy-
      collagen cross-linking treatment for the management of progressive keratoconus,
      radiofrequency treatment for skin rejuvenation, physical extracorporeal shockwave
      therapy for healing of Achilles tendinitis, orthodontic treatment, and
      toothbrushing time to minimize the loss of teeth after exposure to acidic drinks.

PMID- 24730253
TI  - Targeted nanodrugs for cancer therapy: prospects and challenges.
AB  - The recent advent of nanomedicine holds potential to revolutionize cancer
      therapy. This innovative discipline has paved the way for the emergence of a new
      class of drugs based on nanoengineered particles. These "nanodrugs" are designed
      to greatly enhance drug therapeutic indices. First-generation nanodrugs consisted
      of conventional anti-cancer drugs loaded into/onto nanoengineered particles
      (nanocarriers) devoid of targeting features (non-targeted nanodrugs). Non
      targeted nanodrugs have provided the opportunity to carry large amounts of drugs,
      including poorly water-soluble and/or permeable drugs, to several types of
      tumors, improving the therapeutic index with respect to comparable free drugs.
      Although effective, the primary delivery mechanism of non-targeted nanodrugs was
      through passive tissue accumulation, due to pathophysiological differences
      between tumor-associated and healthy vessels, and through non-specific targeting
      of cell subsets, posing the danger of off-target binding and effects. Recently,
      the therapeutic indices of certain anti-cancer drugs were further improved by
      attaching targeting ligands to nanodrugs (targeted-nanodrugs). Targeted-nanodrugs
      selectively bind to cognate receptors expressed on target cells and enter cells
      more efficiently than non-targeted formulations. Although these advancements have
      been sufficiently beneficial to place targeted-nanodrugs into clinical
      development for use in cancer therapy, they also come at a price. The addition of
      ligands to drug-loaded nanocarriers often leads to additional synthesis steps and
      costs, and more complex biological performance relative to ligand-devoid
      nanodrugs. Here, we will discuss the benefits and challenges facing the addition
      of targeting features to nanodrugs for cancer therapy.

PMID- 24730254
TI  - Biological barriers and current strategies for modifying nanoparticle
      bioavailability.
AB  - Nanoparticles are diligently crafted with exacting control over size, shape, and
      composition. The pristine nanoparticles are rigorously characterized in vitro by
      numerous physical and materials science techniques. Immediately after being
      exposed to body fluids, nanoparticles interact with a heterogeneous mixture of
      proteins and numerous different cell types that modify the nanoparticle surface
      and affect their bioavailability. Understanding the mechanisms behind the
      recognition and elimination of these modified nanoparticles is the key to the
      successful translation of nanomaterials from preclinical to clinical
      applications. This paper reviews the anatomy of the primary organs (kidney,
      liver, and spleen) responsible for nanoparticle bioelimination and the components
      of the innate immune system (complement system and scavenger receptors) that
      indirectly and directly recognize nanoparticles as foreign. Recent results using
      PEG as a steric barrier, generating biomimetic nanoparticles, and the effect of
      nanoparticle material properties to increase the bioavailability of nanoparticles
      are presented.

PMID- 24730255
TI  - Mucus as barrier for drug delivery by nanoparticles.
AB  - The use of nanoparticles (NPs) can improve drug delivery in many pharmaceutical
      applications. Compared to conventional compounds, NPs are expected to show better
      tissue penetration and to deliver higher drug amounts more selectively to the
      target site. NP-based formulations are most advanced for parenteral applications
      but they are also used for delivery across mucus-covered epithelial surfaces
      (eye, orogastrointestinal tract, airways, and vagina). The mucus layer represents
      an important barrier for an NP-based delivery system. In this review, mucus
      composition, architecture, and turnover of the mucus layer at different
      anatomical locations are addressed. The influence of particle parameters on mucus
      penetration/permeation is mentioned and examples for mucoadhesive, mucolytic, and
      mucus-penetrating particle systems are listed. While mucoadhesive particles have
      a relatively long history in NP-based drug delivery, mucus penetrating NPs have
      been developed more recently. These particles may be advantageous for drug
      delivery to anatomical sites with high mucus turnover.

PMID- 24730250
TI  - Scaffold design for bone regeneration.
AB  - The use of bone grafts is the standard to treat skeletal fractures, or to replace
      and regenerate lost bone, as demonstrated by the large number of bone graft
      procedures performed worldwide. The most common of these is the autograft,
      however, its use can lead to complications such as pain, infection, scarring,
      blood loss, and donor-site morbidity. The alternative is allografts, but they
      lack the osteoactive capacity of autografts and carry the risk of carrying
      infectious agents or immune rejection. Other approaches, such as the bone graft
      substitutes, have focused on improving the efficacy of bone grafts or other
      scaffolds by incorporating bone progenitor cells and growth factors to stimulate
      cells. An ideal bone graft or scaffold should be made of biomaterials that
      imitate the structure and properties of natural bone ECM, include osteoprogenitor
      cells and provide all the necessary environmental cues found in natural bone.
      However, creating living tissue constructs that are structurally, functionally
      and mechanically comparable to the natural bone has been a challenge so far. This
      focus of this review is on the evolution of these scaffolds as bone graft
      substitutes in the process of recreating the bone tissue microenvironment,
      including biochemical and biophysical cues.

PMID- 24730256
TI  - Nanocarrier-based approaches for treatment and detection of Alzheimer's disease.
AB  - Alzheimer's disease (AD) is the most common neurological disorder in people over
      the age of 65. It has been estimated that in 2010 there were 4.7 million
      individuals aged 65 years or older with AD dementia, and it is projected that the
      total number of individuals with AD dementia in 2050 will be 13.8 million. The
      most commonly believed cause and most frequently studied aspect of AD is the
      aggregation of beta amyloid (Abeta), both as soluble Abeta and in the form of
      extracellular plaque. Treatment options are limited mainly due to the inability
      of drugs to cross the blood-brain barrier. Nanoparticulate drug carriers that
      have been targeted to the brain are able to pass through by virtue of their size,
      surface potential, surface coatings (e.g., polyethylene glycol, polysorbate),
      surface decoration with ligands or antibodies attached toward the receptors on
      the blood-brain barrier. Herein, we discuss the current front-runner nanocarriers
      under investigation for effective delivery of pharmaceuticals active in the
      treatment and detection of AD and their mechanisms and discuss a few of the
      outstanding studies.

PMID- 24730257
TI  - Upconversion nanoparticles in bioassays, optical imaging and therapy.
AB  - Rare-earth doped nanoparticle (RE), termed upconversion nanoparticle (UCNP), is a
      new generation of phosphorescence which has recently attracted significant
      research interest. Due to the unique upconversion properties, UCNP has been
      considered to be an excellent alternative for conventional fluorescence. Since
      its first emergence in mid-1960s, UCNPs have been studied in a wide range of
      fields, including those in biological applications. Owing to its suitable size
      distribution and biocompatibility, UCNP could be conjugated with various kinds of
      biomolecules, resulting in the development of numerous biological platforms such
      as biodetection assays and therapeutic modalities. The unique optical properties
      of UCNP such as prominent luminescence, deep penetration to biological tissues
      without damaging the cells, low background and high resistance to photo-bleaching
      enhance UCNP prospects as an excellent contrast agent in both in vitro and in
      vivo. In this review, we discuss the recent developments of UCNP in bioassays,
      optical imaging, and therapy, also the prospects and challenges of UCNP-based
      detection in the development of biomedical science.

PMID- 24730258
TI  - Multifunctional nanostructured materials for multimodal cancer imaging and
      therapy.
AB  - This paper reviews the recent research and development of multifunctional
      nanostructured materials for multimodal imaging and therapy. The biomedical
      applications for multifunctional imaging, diagnosis and therapy are discussed for
      several nanostructured materials such as polymeric nanoparticles, magnetic
      nanoparticles, gold nanomaterials, carbon materials, quantum dots and silica
      nanoparticles. Due to the unique features of nanostructured materials including
      the large surface area, structural diversity, multifunctionality, and long
      circulation time in blood, these materials have emerged as attractive preferences
      for optimized therapy. Multimodal imaging can be introduced to nanostructured
      materials for precise and fast diagnosis of cancer, which overcomes the
      shortcoming of single-imaging modality. Meanwhile, nanostructured materials can
      be also used to deliver therapeutic agents to the disease site in order to
      accomplish multimodal imaging and simultaneous diagnosis and therapy.

PMID- 24730259
TI  - Ultrasound contrast agents and ultrasound molecular imaging.
AB  - Ultrasound imaging in combination with microbubble contrast agents has
      demonstrated its potential for molecular imaging of vascular targets. In this
      article, we systematically review the technologies related to ultrasound
      molecular imaging. First, we introduce the basic principles of ultrasound
      molecular imaging. Then, we discuss ultrasound microbubble contrast agents. This
      includes selection requirements for targeted contrast agent ligands and
      receptors, targeted ultrasound contrast agent preparation, targeted ultrasound
      contrast agent ligands connection methods, and microbubble ultrasound contrast
      agent safety issues. The use of ultrasound molecular imaging in diagnosis and
      treatment, as well as some issues relating to high intensity focused ultrasound
      and ultrasound molecular imaging applications in disease diagnosis are also
      discussed. Applications include detection of inflammation, thrombus, tumors, and
      neovascularization. Consideration is also given to the acoustic characteristics
      of microbubbles and the acoustic principles underlying microbubble ultrasound
      imaging. Several microbubble scattering models are highlighted (including the
      Rayleigh-Plesset model, the Rayleigh-Plesset-Noltingk-Neppiras-Poritsky model,
      the Herring model, the Marmottant model, and the non-spherical bubble dynamics
      model). The interaction between two microbubbles and the effect of radiation on
      the microbubbles is also discussed. Finally, from an engineering perspective, we
      summarize the techniques used to improve the quality of ultrasound molecular
      images (harmonic imaging, perfusion imaging, and deconvolution technology). It is
      inevitable that ultrasound molecular imaging will continue to mature and can be
      expected to play an increasingly larger role in diagnosis and treatment of human
      diseases in the near future.

PMID- 24730260
TI  - Ultrasmall superparamagnetic iron oxide nanoparticles for magnetic resonance
      imaging contrast agent.
AB  - Nanotechnology has given scientists new tools for the development of advanced
      materials for the detection and diagnosis of various types of diseases. In
      particular, ultrasmall superparamagnetic iron oxides (USPIOs) have been
      investigated in many biological applications, both in vitro and in vivo. Due to
      their small size (diameter < 20 nm), these particles are not immediately removed
      from the circulation by the reticuloendothelial system (RES), have a longer blood
      half-life, a wider biodistribution and allow potential targeting with appropriate
      bioconjugates to specific tissues both normal and tumorous. This review will
      mainly discuss the synthesis of USPIOs and their applications as MRI contrast
      agent for disease detection.

PMID- 24730261
TI  - Optical and structural properties of nanobiomaterials.
AB  - In this review, the optical and structural properties of biomaterials are
      discussed. First, we demonstrate the optical and structural properties of natural
      and plasma-treated DNA, using UV-visible absorption, circular dichroism (CD), and
      Raman spectroscopy. Fluorescence and lasing action in the dye-doped DNA
      surfactant complex are also explained. Additionally, nanomaterial-based DNA
      detection and DNA-templated nanomaterial growth are described. Next, we discuss
      protein folding studies utilizing fluorescence, CD, and nuclear magnetic
      resonance (NMR) spectroscopy. From the CD spectra of alpha-chymotrypsin (CT), we
      estimate the composition of a-helices and the beta-sheets, and random coils in
      the CT. 1H NMR spectroscopy is used to investigate the thermal effect on the
      refolding of CT in the presence of an ionic liquid. Finally, we explain the
      numerical simulation method used for studying the optical properties of
      biomaterials. Applications of the Monte-Carlo method in photodynamic therapy,
      skin tissue optics, and bioimaging are described.

PMID- 24730262
TI  - Polythiophenes in biological applications.
AB  - Polythiophene and its derivatives have shown tremendous potential for interfacing
      electrically conducting polymers with biological applications. These
      semiconducting organic polymers are relatively soft, conduct electrons and ions,
      have low cytotoxicity, and can undergo facile chemical modifications. In
      addition, the reduction in electrical impedance of electrodes coated with
      polythiophenes may prove to be invaluable for a stable and permanent connection
      between devices and biological tissues. This review article focuses on the
      synthesis and some key applications of polythiophenes in multidisciplinary areas
      at the interface with biology. These polymers have shown tremendous potential in
      biological applications such as diagnostics, therapy, drug delivery, imaging,
      implant devices and artificial organs.

PMID- 24730264
TI  - Polymeric micelle as multifunctional pharmaceutical carriers.
AB  - A number of formulations have been developed and reported in literature as a
      carrier for drug, gene, and diagnostic agents. Amphiphilic block copolymers have
      achieved increasing attention due to their high stability both in vitro and in
      vivo and their good biocompatibility. In comparison to other long-circulating
      nanocarriers, micelles possess a number of advantages such as tissue
      penetrability, reduced toxicity, and controlled drug release. The characteristic
      features of micelle as carriers, such as particle size, shape, drug loading,
      cellular internalization, stability, and release kinetics of drugs can be
      improved by altering the physicochemical properties of the constituent block
      copolymers and method of preparation. Polymeric micelles formed from amphiphilic
      blocks have been successfully used for delivery of drugs that lack water
      solubility. Chelation or incorporation of a diagnostic agent in ligand conjugated
      micelle may help in tracing in vivo biodistribution. We review a number of
      research articles demonstrating that micelle formulations can be used efficiently
      in clinical situations by taking care of the toxicity of surfactants, and the
      interaction between polymer and drug, to prepare a formulation carrying a more
      therapeutic agent with a minimum amount of polymer.

PMID- 24730263
TI  - Silicon nanowire biologically sensitive field effect transistors: electrical
      characteristics and applications.
AB  - The interest in biologically sensitive field effect transistors (BioFETs) is
      growing explosively due to their potential as biosensors in biomedical,
      environmental monitoring and security applications. Recently, adoption of silicon
      nanowires in BioFETs has enabled enhancement of sensitivity, device
      miniaturization, decreasing power consumption and emerging applications such as
      the 3D cell probe. In this review, we describe the device physics and operation
      of the silicon nanowire BioFETs along with recent advances in the field. The
      silicon nanowire BioFETs are basically the same as the conventional field-effect
      transistors (FETs) with the exceptions of nanowire channel instead of thin film
      and a liquid gate instead of the conventional gate. Therefore, the silicon device
      physics is important to understand the operation of the BioFETs. Herein, physical
      characteristics of the silicon nanowire FETs are described and the operational
      principles of the BioFETs are classified according to the number of gates and the
      analysis domain of the measured signal. Even the bottom-up process has merits on
      low-cost fabrication; the top-down process technique is highlighted here due to
      its reliability and reproducibility. Finally, recent advances in the silicon
      nanowire BioFETs in the literature are described and key features for
      commercialization are discussed.

PMID- 24730265
TI  - Recent progress in chitosan bio-based soft nanomaterials.
AB  - Polysaccharides are a new class of pervasive biopolymers that display many
      advantages including wide availability, sustainability, inherent inclusion of
      chemical functionality, biocompatibility and biodegradability. Current efforts
      are focused on the catalytic transformation of these macromolecules into fuels
      and platform chemicals. However, there is growing interest in using biopolymers
      directly to create functional materials. Particularly, the ability of some
      polysaccharides to form physical and chemical porous hydrogels has opened new
      avenues for material synthesis and has been the driving force for rethinking the
      strategies used to create value-added nanomaterials from naturally available
      biomass. Among them, chitosan is on the rise due to the presence of amino groups
      on the polymer backbone that distinguishes it as a unique natural cationic
      polymer. This contribution sheds light on the opportunities offered by
      engineering the secondary structure of chitosan fibrillar hydrogels. The
      optimization and stabilization of the open framework structure of these soft
      materials are crucial to designing novel functional hybrid materials, dispersed
      chitosan-metal nanoparticles and hierarchical porous inorganic materials.

PMID- 24730266
TI  - Applications of nanodiamonds in drug delivery and catalysis.
AB  - The interest of researchers in utilizing nanomaterials as carriers for a wide
      spectrum of molecules has exploded in the last two decades. Nanodiamonds are one
      class of carbon-based nanomaterials that have emerged as promising drug delivery
      vehicles and imaging probes. Their ease of functionalization also led to the
      generation of stimuli-responsive nanodiamonds that deliver drugs on demand in a
      controlled manner. The ample surface area of NDs allowed for a higher loading of
      not only small molecules but also macromolecules like genes and proteins.
      Recently, the unique surface of NDs has attracted more attention as catalyst
      support in a huge range of organic modification and C-C bond formation reactions.
      Herein, recent advances in the utilization of nanodiamonds as a drug delivery
      vehicle and catalytical support are highlighted and summarized to illustrate the
      potential and versatility of this cheap and commercially available nanomaterial.

PMID- 24730267
TI  - Biological applications of gold nanoparticles.
AB  - This article reviews some of the recent biological applications of gold
      nanoparticles (GNPs) which have been discovered lately by individual studies all
      around the world. GNPs have emerged as a promising candidates for various
      biological applications due to their unique physical properties (size and shape
      dependent), excellent biocompatibility, facile synthesis, ease of bioconjugation,
      etc. This review starts with a brief introduction about nanotechnology followed
      by an insight into the history, emergence, and enhanced properties of various
      gold nanostructures, which form the basis for their numerous biomedical
      applications. In addition, a brief overview on some of the commonly used
      fabrication techniques for synthesizing GNPs is also discussed. Finally, a
      miscellany of the latest biological applications of GNPs, such as cancer
      diagnostics and therapy, biological probes, drug delivery, gene delivery, vaccine
      preparation, brain implants, artificial skin, sterilization system, and improving
      electrical signaling in the heart, published in different articles in reputed
      journals are highlighted.

PMID- 24730268
TI  - The design and applications of nanoparticle coated microspheres in immunoassays.
AB  - Nanoparticle coated microspheres are composed of two or more materials with a
      core/shell structure and exhibit unique abilities that allow amplification of
      trace targets in immunoassays. The preparation of nanoparticle coated
      microspheres can be accomplished using three main strategies: (1) in-situ, (2) ex
      situ, and (3) hollow sphere methods. Antibodies or biomolecules can be
      immobilized on the surface of nanoparticle coated microspheres or hollow spheres
      to carry out detection of targets using surface-enhanced resonance spectroscopy
      (SERS), fluorescence, electrochemistry, and many others. Using these particles as
      antibody carriers in SERS-based immunoassays, broad dynamic range and low
      detection limits, and improved selectivity can be realized. By assistance of
      nanoparticle coated microspheres in immunoassays, improved sensitivity and
      selectivity has been realized. In this review, nanoparticle coated microsphere
      generation, recent applications, and future potential with respect to
      immunoassays are discussed.

PMID- 24730269
TI  - Disposable biosensors for clinical diagnosis.
AB  - We present an overview on the use of disposable electrochemical biosensors for
      diagnostics, focusing on the applications of these devices as immunosensors and
      DNA sensors in the point-of-care diagnostics. Analytical biosensors have emerged
      as efficient alternatives for the detection of innumerous diseases, because of
      their high specificity and the convenience of detecting the electrochemical
      signals produced by the presence of an analyte using a portable equipment. This
      review highlights the recently developed strategies toward immobilization of
      different biological molecules on disposable electrodes such as carbon nanotubes
      and metal nanoparticles. In the course of the review, we first introduced the
      disposable biosensors, followed by an overview of the immunosensors, and
      discussed the applications of DNA sensors and disposable biosensors in point-of
      care diagnostics. We also have evaluated the prospects and future applications of
      these devices in the field of biomedical research.

PMID- 24730270
TI  - Nanoarchitectonics of molecular aggregates: science and technology.
AB  - The field of making, studying and using molecular aggregates, in which the
      individual molecules (monomers) are arranged in a regular fashion, has come a
      long way. Taking control over the aggregation of small molecules and polymers in
      bulk, on surfaces and at interfaces pose a considerable challenge for their
      utilization in modern high tech applications. In this review, we provide a
      detailed insight into recent trends in molecular aggregates from the perspectives
      of nanoarchitectonics.

PMID- 24730271
TI  - Biophysicochemical perspective of nanoparticle compatibility: a critically
      ignored parameter in nanomedicine.
AB  - Engineered nanomaterials are increasingly used in domestic and commercial
      products due to the rapid growth and increasing public and industrial interests
      in nanotechnology. Undoubtedly there will be more exposure of living organisms
      and the environment to nanomaterials. Therefore, understanding the
      biophysicochemical interactions of nanoparticles with proteins, membranes, cells,
      DNA, and organelles at the nano-biointerface will help to control fundamental
      biological and dynamic colloidal forces to promote biocompatibility of the
      particles. In this article, we review how bio- and physicochemical surface
      characteristics at nanoscale govern particle biocompatibility for in vivo and in
      vitro models. We also revisit the promise and predictions gained from this
      understanding to design special types of nanoparticles, such as quantum dots
      (QDs) and superparamagnetic iron oxide nanoparticles (SPIONs), for biomedical
      applications. This knowledge is essential not only from the perspective of safe
      use of nanomaterials, but also in paving the way for nontoxic interactions with
      biological systems. It paves the route for safe implementation of the materials
      in novel biomedical diagnostics and therapeutics. We also put forward an outlook
      and future perspective, which are largely "ignored parameters" in nanomedicine.
      In conclusion, emphasis on the systematic evaluation of nanomaterial toxicity in
      primary cells derived from vital organs and the need to develop an international
      consortium for a materialomics database is encouraged.

PMID- 24730272
TI  - Functional nanoparticles in targeting glioma diagnosis and therapies.
AB  - Successful therapy and diagnosis of glioma is one of the biggest challenges in
      the biomedical fields. The incidence is growing gradually around the world.
      Annually, there are approximately 13,000 cases of glioblastoma multiforme
      diagnosed with historical 1-year and 5-year survival rates of 29.3% and 3.3%,
      respectively. The prognosis of patients with malignant glioma remains dismal. Due
      to its highly proliferative, infiltrative, and invasive property, development of
      effective preventative strategies to control the gliomas is in high demand.
      Meanwhile, the efficiency of drug delivery to glioma remains low owing to the non
      specific, non-targeted nature of anti-tumor agents. Furthermore, the presence of
      the blood brain barrier and blood brain tumor barrier is another obstacle for
      gliomas treatments. Nanotechnology has brought a paradigm shift in the diagnosis
      and treatment of glioma. This review discusses the potential of various
      nanoparticles in the diagnosis of gliomas using some metal oxide, and in the
      therapy of gliomas including receptor-mediated, magnetic directing, and cell
      mediated drug delivery systems. In this review, some physical techniques combined
      with nanoparticles (NPs) such as ultrasound therapy, thermochemotherapy,
      photodynamic therapy, and fluorescent magnetic NPs have also been summarized.

PMID- 24730273
TI  - Recombinant protein-based nanoscale biomemory devices.
AB  - Biomolecular computing devices that are based on the properties of biomolecular
      activities offer a unique possibility for constructing new computing structures.
      A new concept of using various biomolecules has been proposed in order to develop
      a protein-based memory device that is capable of switching physical properties
      when electrical input signals are applied to perform memory switching. To clarify
      the proposed concept, redox protein is immobilized on Au nanoelectrodes to
      catalyze reversible reactions of redox-active molecules, which is controlled
      electrochemically and reversibly converted between its ON/OFF states. In this
      review, we summarize recent research towards developing nanoscale biomemory
      devices including design, synthesis, fabrication, and functionalization based on
      the proposed concept. At first we analyze the memory function properties of the
      proposed device at bulk material level and then explain the WORM (write-once-read
      many times) nature of the device, later we extend the analysis to multi-bit and
      multi-level storage functions, and then we focus the developments in nanoscale
      biomemory devices based on the electron transport of redox molecules to the
      underlying Au patterned surface. The developed device operates at very low
      voltages and has good stability and excellent reversibility, proving to be a
      promising platform for future memory devices.

PMID- 24730274
TI  - Surface modified quantum dots as fluorescent probes for biomolecule recognition.
AB  - The development of novel nanomaterial-based analytical methods for biological
      analysis in proteomics and clinical diagnosis has been making significant
      progress. In the long-lasting efforts to improve the detection sensitivity of
      analytical instruments, functional nanomaterials have been significantly applied
      as effective probes by integrating various analytical tools for bioanalysis.
      Among these nanomaterials, quantum dots (QDs) have been recently proved as highly
      potential materials as fluorescent sensors for biomolecules assays due to their
      high quantum yield, narrow and tunable emission spectrum and excellent
      photostability. In this review, we introduce the use of surface modified QDs as
      fluorescence probes for detecting proteins, peptides and other biomolecules based
      on fluorescence quenching and fluorescence resonance energy transfer (FRET).

PMID- 24730275
TI  - Endosomal escape: a bottleneck in intracellular delivery.
AB  - With advances in therapeutic science, apart from drugs, newer bioactive moieties
      like oligonucleotides, proteins, peptides, enzymes and antibodies are constantly
      being introduced for the betterment of therapeutic efficacy. These moieties have
      intracellular components of the cells like cytoplasm and nucleus as one of their
      pharmacological sites for exhibiting therapeutic activity. Despite their
      promising efficacy, their intracellular bioavailability has been critically
      hampered leading to failure in the treatment of numerous diseases and disorders.
      The endosomal uptake pathway is known to be a rate-limiting barrier for such
      systems. Bioactive molecules get trapped in the endosomal vesicles and degraded
      in the lysosomal compartment, necessitating the need for effective strategies
      that facilitate the endosomal escape and enhance the cytosolic bioavailability of
      bioactives. Microbes like viruses and bacteria have developed their innate
      mechanistic tactics to translocate their genome and toxins by efficiently
      penetrating the host cell membrane. Understanding this mechanism and exploring it
      further for intracellular delivery has opened new avenues to surmount the
      endosomal barrier. These strategies include membrane fusion, pore formation and
      proton sponge effects. On the other hand, progress in designing a novel smart
      polymeric carrier system that triggers endosomal escape by undergoing modulations
      in the intracellular milieu has further led to an improvement in intracellular
      delivery. These comprise pH, enzyme and temperature-induced modulators, synthetic
      cationic lipids and photo-induced physical disruption. Each of the aforementioned
      strategies has its own unique mechanism to escape the endosome. This review
      recapitulates the numerous strategies designed to surmount the bottleneck of
      endosomal escape and thereby achieve successful intracellular uptake of
      bioactives.

PMID- 24730276
TI  - Zinc oxide nanomaterials for biomedical fluorescence detection.
AB  - One-dimensional zinc oxide nanomaterials have been recently developed into novel,
      extremely effective, optical signal-enhancing bioplatforms. Their usefulness has
      been demonstrated in various biomedical fluorescence assays. Fluorescence is
      extensively used in biology and medicine as a sensitive and noninvasive detection
      method for tracking and analyzing biological molecules. Achieving high
      sensitivity via improving signal-to-noise ratio is of paramount importance in
      fluorescence-based, trace-level detection. Recent advances in the development of
      optically superior one-dimensional materials have contributed to this important
      biomedical area of detection. This review article will discuss major research
      developments that have so far been made in this emerging and exciting topical
      field. The discussion will cover a broad range of subjects including synthesis of
      zinc oxide nanorods (ZnO NRs), various properties differentiating them as
      suitable optical biodetection platforms, their demonstrated applicability in DNA
      and protein detection, and the nanomaterial characteristics relevant for
      biomolecular fluorescence enhancement. This review will then summarize the
      current status of ZnO NR-based biodetection and further elaborate future utility
      of ZnO NR platforms for advanced biomedical assays, based on their proven
      advantages. Lastly, present challenges experienced in this topical area will be
      identified and focal subject areas for future research will be suggested as well.

PMID- 24730277
TI  - The use of microtechnology and nanotechnology in fabricating vascularized
      tissues.
AB  - Tissue engineering (TE) is a multidisciplinary research area that combines
      medicine, biology, and material science. In recent decades, microtechnology and
      nanotechnology have also been gradually integrated into this field and have
      become essential components of TE research. Tissues and complex organs in the
      body depend on a branched blood vessel system. One of the main objectives for TE
      researchers is to replicate this vessel system and obtain functional vascularized
      structures within engineered tissues or organs. With the help of new
      nanotechnology and microtechnology, significant progress has been made.
      Achievements include the design of nanoscale-level scaffolds with new
      functionalities, development of integrated and rapid nanotechnology methods for
      biofabrication of vascular tissues, discovery of new composite materials to
      direct differentiation of stem and inducible pluripotent stem cells into the
      vascular phenotype. Although numerous challenges to replicating vascularized
      tissue for clinical uses remain, the combination of these new advances has
      yielded new tools for producing functional vascular tissues in the near future.

PMID- 24730278
TI  - Strategies for combination of aptamer and targeted drug delivery.
AB  - Cell-specific delivery of active agents for treatment of human disease is a long
      cherished object for scientific researchers. Nanoscience generated nanosized
      carriers, such as liposome, micelle and nanoparticle, provides potential to
      realize such purpose based on the nanometer size effect (< 1000 nm), however, the
      sole nanocarrier with no specific ligands are not sufficient to deliver drugs to
      target sites. Aptamers are single-stranded oligonucleotides which can
      specifically recognize and bind to target cells by distinct secondary and
      tertiary structures even without knowledge of characteristic protein profiles on
      cell surface. Thus, aptamer, as a target moiety, provides a potential approach to
      realize pathological site-specific delivery of active agents. This review
      highlighted the strategies for combination of aptamer and targeted drug delivery,
      further summarized their preparation methods, strengths and weaknesses to
      facilitate the development of targeted drug delivery system.

PMID- 24730279
TI  - Neurons on nanotopographies: behavioral responses and biological implications.
AB  - Neural cells are well known to be affected by the topographical features of the
      surfaces to which they adhere. There have been numerous reports showing guided
      neurite extension on microgrooves and micropillar arrays made of a wide range of
      materials. However, it has recently been disclosed that neural cells on
      nanotopographies exhibit much more derivatized and complicated responses than
      just neurite guidance. Nevertheless, the biological mechanisms for these
      responses are not yet understood. In this review, we categorized the responses of
      neurons to nanotopographies into three groups (adhesion, neurite guidance, and
      developmental acceleration). In addition, we also tried to elicit biological
      implications about the mechanisms for the recognition of nanotopographies.
      Further investigation of neuronal responses to nanotopographies would highly
      inspire both fundamental research about neuronal development and practical
      applications related to neuro-regeneration.

PMID- 24730280
TI  - Electrospun nanofibers: from filtration membranes to highly specialized tissue
      engineering scaffolds.
AB  - Electrospinning is a widely used technique to produce continuous polymeric fibers
      ranging from 2 nm to several micrometers. This technique is not only employed in
      research laboratories, but it is also increasingly being applied in different
      industrial fields in the last few decades as a highly versatile and cost
      effective technology. Compared to conventional techniques for fiber fabrication,
      electrospinning can fabricate fibers in a more desirable size (e.g., nanoscale).
      Nanofibers are generated by the application of a strong electric field on polymer
      solution. Over the years, more than 200 polymers have been electrospun for
      various applications. In this review, our aim was to present an overview of the
      electrospinning technique and its potential applications. We covered the basic
      principles of the electrospinning technique and parameters which significantly
      affect the fiber morphology. The most recent work on electrospinning nanofibers
      for blending polymers, filtration, energy, sensing and biomedical applications
      was also presented in this review.

PMID- 24730281
TI  - Poly(epsilon-caprolactone) nanocomposite scaffolds for tissue engineering: a
      brief overview.
AB  - Polycaprolactone is a bioresorbable polymer that has been extensively used in the
      biomaterials field and a number of drug-delivery systems. The superior
      rheological and viscoelastic properties of this polymer render it easy to
      manufacture and manipulate into a large range of medical devices and implants.
      The advantage of polycaprolactone over its aliphatic counterparts is that it has
      a long-term degradation period, which provides a good platform for the design and
      fabrication of implants that require long-term degradation kinetics for example
      in bone tissue engineering. The incorporation of nanofillers or blending of
      polycaprolactone with other polymers has yielded a class of hybrid materials with
      significantly improved physical and chemical properties such as strength,
      porosity, microstructure, controllable degradation rates, and bioactivity that
      are important for tissue engineering. This overview highlights the interesting
      advancements in polycaprolactone polymeric systems that relate to biological and
      tissue engineering applications, including aspects of technology in fabricating
      the scaffolds.

PMID- 24730282
TI  - Isolation and preparation of nanoscale bioapatites from natural sources: a
      review.
AB  - This review summarizes recent work on isolating and preparing bioapatites from
      various natural sources. First, the physicochemical properties of bioapatites are
      described and discussed. Then, a general summary of natural (animals and
      vegetals) sources for bioapatite production from various environments
      (terrestrial and water) is made. Special attention is paid to describing
      individual methods for acquiring bioapatite from biogenic sources, e.g., direct
      isolation of bioapatite, or indirect biomimetic synthesis, with the aid of
      naturally derived biomolecules or biomembranes. The results of a comprehensive
      physicochemical characterization and a biological evaluation (in vitro and in
      vivo) for bioapatites and their applications in clinical practice are presented.
      Finally, future perspectives are summarized and discussed.

PMID- 24730283
TI  - Chemical modification of chitosan with pH-sensitive molecules and specific
      ligands for efficient DNA transfection and siRNA silencing.
AB  - Successful gene therapy depends on the development of efficient and cell-specific
      gene delivery systems. Currently, animal viral vectors have been mostly used for
      in vivo and in clinical trials owing to their high transduction efficiency.
      However, they suffer from numerous limitations such as biosafety, immunogenicity,
      gene packaging capacity, complicated production and cell specificity. Therefore
      non-viral vectors are attractive alternatives to viral gene delivery systems due
      to their low toxicity, relatively easy production and greater diversity. Among
      non-viral vectors, chitosan and chitosan derivatives have been extensively
      utilized as gene carriers owing to their low immunogenicity, biocompatibility,
      biodegradability, low toxicity and ease of chemical modifications. However, low
      transfection efficiency of DNA (or low gene silencing of siRNA) and low cell
      specificity of chitosan should be overcome before clinical trials. The objective
      of this review is to summarize several parameters affecting the transfection
      efficiency of DNA (or gene silencing of siRNA) for the promising use of chitosan
      as gene carriers. Besides, chemical modifications of chitosan with pH-sensitive
      molecules and specific ligands so as to enhance the transfection efficiency of
      DNA (or gene silencing of siRNA) and cell specificity will be covered.

PMID- 24730284
TI  - The role of functionalized magnetic iron oxide nanoparticles in the central
      nervous system injury and repair: new potentials for neuroprotection with
      Cerebrolysin therapy.
AB  - Functionalized Magnetic Iron Oxide Nanoparticles (FMIONPs) are being explored for
      the development of various biomedical applications, e.g., cancer chemotherapy
      and/or several other radiological or diagnostic purposes. However, the effects of
      these NPs per se on the central nervous system (CNS) injury or repair are not
      well known. This review deals with different aspects of FMIONPs in relation to
      brain function based on the current literature as well as our own investigation
      in animal models of CNS injuries. It appears that FMIONPs are innocuous when
      administered intravenously within the CNS under normal conditions. However,
      abnormal reactions to FMIONPs in the brain or spinal cord could be seen if they
      are combined with CNS injuries e.g., hyperthermia or traumatic insults to the
      brain or spinal cord. Thus, administration of FMIONPs in vivo following whole
      body hyperthermia (WBH) or a focal spinal cord injury (SCI) exacerbates cellular
      damage. Since FMIONPs could help in diagnostic purposes or enhance the biological
      effects of radiotherapy/chemotherapy it is likely that these NPs may have some
      adverse reaction as well under disease condition. Thus, under such situation,
      adjuvant therapy e.g., Cerebrolysin (Ever NeuroPharma, Austria), a suitable
      combination of several neurotrophic factors and active peptide fragments are the
      need of the hour to contain such cellular damages caused by the FMIONPs in vivo.
      Our observations show that co-administration of Cerebrolysin prevents the FMIONPs
      induced pathologies associated with CNS injuries. These observations support the
      idea that FMIONPs are safe for the CNS in disease conditions when co-administered
      with cerebrolysin. This indicates that cerebrolysin could be used as an adjunct
      therapy to prevent cellular damages in disease conditions where the use of
      FMIONPs is required for better efficacy e.g., cancer treatment.

PMID- 24730285
TI  - Nanostructured conducting polymers and their biomedical applications.
AB  - Much attention has been paid to nanostructured conducting polymers due to their
      unique properties, which arise from their nanoscale size, such as their large
      surface area, high electrical conductivity, electrochemical stability and quantum
      effects. This article reviews three methods to synthesize nanostructured
      conducting polymers and their applications in the biomedical field, focusing
      specifically on neural probes, biosensors, artificial muscles or actuators and
      controlled drug release. Challenges and future directions of these nanostructured
      conducting polymer are also discussed.

PMID- 24730286
TI  - Applications of nanotechnology in wastewater treatment--a review.
AB  - Water on Earth is a precious and finite resource, which is endlessly recycled in
      the water cycle. Water, whose physical, chemical, or biological properties have
      been altered due to the addition of contaminants such as organic/inorganic
      materials, pathogens, heavy metals or other toxins making it unsafe for the
      ecosystem, can be termed as wastewater. Various schemes have been adopted by
      industries across the world to treat wastewater prior to its release to the
      ecosystem, and several new concepts and technologies are fast replacing the
      traditional methods. This article briefly reviews the recent advances and
      application of nanotechnology for wastewater treatment. Nanomaterials typically
      have high reactivity and a high degree of functionalization, large specific
      surface area, size-dependent properties etc., which makes them suitable for
      applications in wastewater treatment and for water purification. In this article,
      the application of various nanomaterials such as metal nanoparticles, metal
      oxides, carbon compounds, zeolite, filtration membranes, etc., in the field of
      wastewater treatment is discussed.

PMID- 24730287
TI  - Removal of water contaminants by iron oxide nanomaterials.
AB  - In recent years, there has been increasing concern about the usage of a broad
      range of organic substances, heavy metals and aromatic compounds in the aquatic
      environment due to their wide distribution and potential adverse health effects.
      The presence of toxic contaminants in water effluent, even at very low
      concentrations, is extremely harmful and undesirable. Various treatment processes
      have been investigated to reduce these toxic pollutants from wastewater. Because
      of the chemical stability of the contaminants, these technologies have proved to
      be ineffective for handling waste effluents. Nanotechnology offers the
      possibility of efficient removal of pollutants as nanoparticles have a smaller
      size and higher adsorptive surface area. From the past few years, nanoscale iron
      oxides such as magnetite, maghemite, and hematite have been used for the
      separation and removal of organic and inorganic contaminants. In this review we
      summarize the use of iron oxide nanomaterials performed over the last few years
      for the removal of dyes, heavy metals and aromatic compounds.

PMID- 24730288
TI  - Green chemistry of carbon nanomaterials.
AB  - The global trend of looking for more ecologically friendly, "green" techniques
      manifested itself in the chemistry of carbon nanomaterials. The main principles
      of green chemistry emphasize how important it is to avoid the use, or at least to
      reduce the consumption, of organic solvents for a chemical process. And it is
      precisely this aspect that was systematically addressed and emphasized by our
      research group since the very beginning of our work on the chemistry of carbon
      nanomaterials in early 2000s. The present review focuses on the results obtained
      to date on solvent-free techniques for (mainly covalent) functionalization of
      fullerene C60, single-walled and multi-walled carbon nanotubes (SWNTs and MWNTs,
      respectively), as well as nanodiamonds (NDs). We designed a series of simple and
      fast functionalization protocols based on thermally activated reactions with
      chemical compounds stable and volatile at 150-200 degrees C under reduced
      pressure, when not only the reactions take place at a high rate, but also excess
      reagents are spontaneously removed from the functionalized material, thus making
      its purification unnecessary. The main two classes of reagents are organic amines
      and thiols, including bifunctional ones, which can be used in conjunction with
      different forms of nanocarbons. The resulting chemical processes comprise
      nucleophilic addition of amines and thiols to fullerene C60 and to defect sites
      of pristine MWNTs, as well as direct amidation of carboxylic groups of oxidized
      nanotubes (mainly SWNTs) and ND. In the case of bifunctional amines and thiols,
      reactions of the second functional group can give rise to cross-linking effects,
      or be employed for further derivatization steps.

PMID- 24730289
TI  - Antimicrobial nanocomposites based on natural modified materials: a review of
      carbons and clays.
AB  - The review is focused on the recent research and development of antimicrobial
      nanocomposites based on selected carbon nanomaterials and natural nanoclay
      minerals. The nanocomposites comprised of two or several components, where at
      least one presents antimicrobial properties, are discussed. Yet the most popular
      agent remains silver as nanoparticle or in ionic form. Second, broadly studied
      group, are organics as additives or polymeric matrices. Both carbons and clays in
      certain forms possess antimicrobial properties. A lot of interest is put on to
      research graphene oxide. The low-environmental impact technologies-based on
      sustainable biopolymers have been studied. Testing of antimicrobial properties of
      nanomaterials is performed most frequently on E. coli and S. aureus bacterias.

PMID- 24730290
TI  - Carbohydrate-based nanogels as drug and gene delivery systems.
AB  - Nanogels are hydrogels with nanometer-scale three-dimensional networks of
      physically or chemically cross-linked chains. Nanogels have attracted much
      interest in recent years for various biomedical applications such as drug
      delivery systems and bioimaging owing to their specific properties of size
      tunability and intrinsic hydrophilic surfaces. Nanogels are generally classified
      either as natural polymer-based or synthetic polymer-based nanogels. Natural
      polymer-based nanogels are considered better candidates for drug delivery than
      synthetic polymer-based nanogels. This review summarizes the role of natural
      polymer-based nanogels, especially carbohydrate-based nanogels as drug and gene
      delivery systems.

PMID- 24730291
TI  - Nanoencapsulation of cells within multilayer shells for biomedical applications.
AB  - This paper reviews the recent research and development of the systems of nano
      thin layers coated cells for biomedical applications. Polyelectrolyte based nano
      thin polymer coatings, due to their individual layered structure and
      functionalization ability, are a promising part of the systems involving cells
      for biological processes regulation. The purpose of the layer-by-layer coating
      technique application is to minimize capsule void volume and separate cells from
      the host immunological system eliminating immunosuppressive therapy during
      transplantation. The materials for polyelectrolyte shells and their
      modifications, followed by the techniques of forming polymer nano-thin coatings
      are briefly introduced. The enhanced properties of cell nanocoatings are then
      discussed, involving usability for encapsulation of live cells, immunological
      barrier, and coatings detection among others. The systems utilizing layer-by
      layer coatings without cell participation are briefly mentioned. Finally, the
      perspectives for the future are discussed in terms of limitations and application
      in biomedicine.

PMID- 24730292
TI  - Toxicological properties of nanomaterials.
AB  - The development of engineered nanomaterials opens tremendous opportunities for
      their application as therapeutic and diagnostic tools, as well as in the fields
      of consumer products. As the newly developed material subtype, they exhibit great
      activities for the high ratio of surface to total atoms. In the bio-system, the
      activity can render nanomaterials some negative outcomes for their unexpected
      deposition in organs and cells, the cellular response to the exogenous substance
      and the interfacial reaction with biomolecules. In this review, we have discussed
      the evolution of nanotoxicology studies in the past ten years mainly emerging
      from our laboratory. The early in vivo studies mainly focused on the biokinetic
      of inhaled nanoparticles and their impacts on mammal tissues, such as the central
      nervous system, respiratory system, cardiovascular system and so on. Then the
      scope extended to engineered nanomaterials used as food additives and medicines,
      as well as their influence on alimentary and reproductive systems. In vitro
      experiments to study the nanoparticle-cell interaction and nanoparticle
      biomolecule interplay are indispensable to reveal the mechanisms behind the
      macroscopic phenomenon. In addition, novel tools such as new model organisms and
      synchrotron radiation-based techniques are used to facilitate our understanding
      of the toxicology profile of nanomaterials.

PMID- 24730293
TI  - Nanotoxicity: oxidative stress mediated toxicity of metal and metal oxide
      nanoparticles.
AB  - Metal and metal oxide nanoparticles are often used as industrial catalysts or to
      improve product's functional properties. Recent advanced nanotechnology have been
      expected to be used in various fields, ranging from sensors, environmental
      remediation to biomedicine, medical biology and imaging, etc. However, the
      growing use of nanoparticles has led to their release into environment and
      increased levels of these particles at nearby sites or the surroundings of their
      manufacturing factories become obvious. The toxicity of metal and metal oxide
      nanoparticles on humans, animals, and certainly to the environment has become a
      major concern to our community. However, controversies still remain with respect
      to the toxic effects and the mechanisms of these nanoparticles. The scientific
      community now feels that an understanding of the toxic effects is necessary to
      handle these nanoparticles and their use. A new discipline, named nanotoxicology,
      has therefore been developed that basically refers to the study of the
      interactions of nanoparticles with biological systems and also measures the
      toxicity level related to human health. Nanoparticles usually generate reactive
      oxygen species to a greater extent than micro-sized particles resulting in
      increased pro-inflammatory reactions and oxidative stress via intracellular
      signaling pathways. In this review, we mainly focus on the routes of exposure of
      some metal and metal oxide nanoparticles and how these nanoparticles affect us or
      broadly the cells of our organs. We would also like to discuss the responsible
      mechanism(s) of the nanoparticle-induced reactive oxygen species mediated organ
      pathophysiology. A brief introduction of the characterization and application of
      these nanoparticles has also been included in the article.

PMID- 24730294
TI  - Interaction of nanomaterials with cells and their medical applications.
AB  - Many studies have been conducted on the development of nanomaterials for medical
      applications. The interaction of nanomaterials with human cells is the most
      important criterion for biomedical application and has been studied in detail.
      Three common approaches have been suggested for nanomaterial mechanisms for
      cellular interaction and internalization: direct diffusion or disruption to the
      plasma membrane, endocytosis, and entry through ion channels and transporter
      proteins. Several important factors affect the interaction and cellular uptake of
      nanomaterials: size, shape, rigidity, surface properties, cell type, and
      endocytotic pathways. In this review, we summarize the mechanisms of cell
      nanomaterial interactions, and the various factors that influence these
      interactions. The importance of proper cell-nanomaterial interaction for medical
      research applications is also highlighted. The results summarized in this review
      may add new dimensions to our understanding of cell-nanomaterial interactions and
      their applications in therapeutic and diagnostic techniques for biomedical,
      academic, and industrial research.

PMID- 24730295
TI  - Liposomes: versatile and biocompatible nanovesicles for efficient biomolecules
      delivery.
AB  - Since the revolutionary discovery that phospholipids can form closed bilayered
      structures in aqueous systems, liposomes have become a very interesting topic of
      research. Because of their versatility and amazing biocompatibility, the use of
      liposomes has been widely accepted in many scientific disciplines. Their
      applications, especially in medicine, have yielded breakthroughs with anticancer
      drug carriers over the past few decades. Specifically, their easy preparation and
      various structural aspects have given rise to a broadly usable way to internalize
      biomolecules such as drugs, DNA, RNA and even imaging probes. This review article
      reports recent developments in liposomal drug delivery and gene delivery, and
      thoroughly covers the synthesis and different kinds of liposomal surface
      modification techniques that have resulted in higher stability and efficiency
      with respect to the use of liposomes in tumor cell targeting, site-specific
      release, and extending blood retention times.

PMID- 24730296
TI  - Nanoparticles and blood-brain barrier: the key to central nervous system
      diseases.
AB  - Major central nervous system disorders represent a significant and worldwide
      public health problem. In fact, the therapeutic success of many pharmaceuticals
      developed to treat central nervous system diseases is still moderate, since the
      blood-brain barrier (BBB) limits the access of systemically administered
      compounds to the brain. Therefore, they require the application of a large total
      dose of a drug, and cause numerous toxic effects. The development of
      nanotechnological systems are useful tools to deliver therapeutics and/or
      diagnostic probes to the brain due to nanocarriers having the potential to
      improve the therapeutic effect of drugs and to reduce their side effects. This
      review provides a brief overview of the variety of carriers employed for central
      nervous system drug and diagnostic probes delivery. Further, this paper focuses
      on the novel nanocarriers developed to enhance brain delivery across the blood
      brain barrier. Special attention is paid to liposomes, micelles, polymeric and
      lipid-based nanoparticles, dendrimers and carbon nanotubes. The recent
      developments in nanocarrier implementation through size/charge optimization and
      surface modifications (PEGylation, targeting delivery, and coating with
      surfactants) have been discussed. And a detailed description of the nanoscaled
      pharmaceutical delivery devices employed for the treatment of central nervous
      system disorders have also been defined. The aim of the review is to evaluate the
      nanotechnology-based drug delivery strategies to treat different central nervous
      system disorders.

PMID- 24730297
TI  - Antimicrobial and biocompatible properties of nanomaterials.
AB  - The rapid development of drug-resistant characteristics in pathogenic viral,
      bacterial, and fungal species and the consequent spread of infectious diseases
      are currently receiving serious attention. Indeed, there is a pressing demand to
      explore novel materials and develop new strategies that can address these issues
      of serious concern. Nanomaterials are currently proving to be the most capable
      therapeutic agents to cope with such hazards. The exceptional physiochemical
      properties and impressive antimicrobial capabilities of nanoparticles have
      provoked their utilization in biomedical fields. Nanomaterials of both organic
      and inorganic nature have shown the capabilities of disrupting microbial cells
      through different mechanisms. Along with the direct influence on the microbial
      cell membrane, DNA and proteins, these nanomaterials produce reactive oxygen
      species (ROS) that damage cell components and viruses. Currently, a serious
      hazard associated with these antimicrobial nanomaterials is their toxicity to
      human and animal cells. Extensive studies have reported the dose, time, and cell
      dependent toxicology of various nanomaterials, and some have shown excellent
      biocompatible properties. Nevertheless, there is still debate regarding the use
      of nanomaterials for medical applications. Therefore, in this review, the
      antimicrobial activities of various nanomaterials with details of their acting
      mechanisms were compiled. The relative toxic and biocompatible behavior of
      nanomaterials emphasized in this study provides information pertaining to their
      practical applicability in medical fields.

PMID- 24730298
TI  - Recent advances in nanosized Mn-Zn ferrite magnetic fluid hyperthermia for cancer
      treatment.
AB  - This paper reviews the recent research and development of nanosized manganese
      zinc (Mn-Zn) ferrite magnetic fluid hyperthermia (MFH) for cancer treatment. Mn
      Zn ferrite MFH, which has a targeted positioning function that only the
      temperature of tumor tissue with magnetic nanoparticles can rise, while normal
      tissue without magnetic nanoparticles is not subject to thermal damage, is a
      promising therapy for cancer. We introduce briefly the composition and properties
      of magnetic fluid, the concept of MFH, and features of Mn-Zn ferrite magnetic
      nanoparticles for MFH such as thermal bystander effect, universality, high
      specific absorption rate, the targeting effect of small size, uniformity of
      hyperthermia temperature, and automatic temperature control and constant
      temperature effect. Next, preparation methods of Mn-Zn ferrite magnetic fluid are
      discussed, and biocompatibility and biosecurity of Mn-Zn ferrite magnetic fluid
      are analyzed. Then the applications of nanosized Mn-Zn ferrite MFH in cancer are
      highlighted, including nanosized Mn-Zn ferrite MFH alone, nanosized Mn-Zn ferrite
      MFH combined with As2O3 chemotherapy, and nanosized Mn-Zn ferrite MFH combined
      with radiotherapy. Finally, the combination application of nanosized Mn-Zn
      ferrite MFH and gene-therapy is conceived, and the challenges and perspectives
      for the future of nanosized Mn-Zn ferrite MFH for oncotherapy are discussed.

PMID- 24730299
TI  - Multifunctional polymeric nanocurcumin for cancer therapy.
AB  - Nanotechnology-based drug delivery systems have the potential to enhance the
      efficacy of poorly soluble systemic drugs. Curcumin, a yellow pigment isolated
      from turmeric, possesses a wide range of pharmacological activities, including
      anticancer effects. The anticancer potential of curcumin is mediated through the
      inhibition and modulation of several intracellular signaling pathways, as
      confirmed in various in vitro and in vivo cancer studies. However, clinical
      application of dietary curcumin for the treatment of cancer and other chronic
      diseases have been hindered by poor bioavailability, due to low systemic
      solubility as well as rapid metabolism and elimination from the body. Different
      techniques for sustained and efficient curcumin delivery, including
      nanoparticles, liposomes, micelles, phospholipids, and curcumin-encapsulated
      polymer nanoparticles are the focus of this study. Previous studies have shown
      that nanocurcumin has improved anticancer effects as compared to normal curcumin
      formulations. Among nanoformulations, few composite nanosystems have the
      simultaneous properties of therapeutic activity and multifunctional nanoparticles
      as enhanced image contrast agents. We also address the challenges to the
      development of nanocurcumin delivery platforms by enhancing a steady aqueous
      dispersion state. Further studies are needed using preclinical and clinical
      cancer models to recommend nanocurcumin as a drug of choice for cancer therapy.

PMID- 24730300
TI  - Polymer conjugate-based nanomaterials for drug delivery.
AB  - The structure of polymeric amphiphiles with both hydrophilic and hydrophobic
      groups forming self-assembled nanoparticles have attracted increasing attention
      in studies of delivery systems of therapeutic agents. An amphiphilic carrier for
      self-assembly in an aqueous solution is preferable because of its structure with
      a hydrophobic core and hydrophilic outer shell, which can be applied to many
      biotechnological and pharmaceutical fields with numerous types of drugs. An
      amphiphilic carrier for self-assembly also represents the most appealing delivery
      system owing to its exceptional advantages in selectively delivering drugs to
      tumor cells and thus, reduction of side effects. This paper reviews two types of
      self-assembled nanoparticles/micelles of conjugated polymeric amphiphiles: (1)
      self-assembled micelles/nanoparticles of amphiphilic conjugates followed by drug
      loading and (2) self-assembled micelles/nanoparticles of polymer-drug conjugates
      where a conjugation reaction occurs between the polymer and drug. The development
      of the research has been addressed in this review with up-to-date references. In
      conclusion, the challenges and remaining difficulties for the future development
      are discussed.

PMID- 24730301
TI  - Nanoarchitectonics in cancer therapy and imaging diagnosis.
AB  - Nanoarchitectonics has gained remarkable importance due to the fabrication of
      various recent nanostructures with the capability of being used in biomedical
      science, particularly in cancer diagnosis and treatment. These nanosized
      structures possess unique physical and optical properties that can be exploited
      for cancer therapeutics, and so nanoarchitectonics is popularly known as
      nanomedicine. The goal of this review is to discuss the latest findings in
      nanostructures research including nanocrystals, nanotubes, nanoshells,
      nanopillars, nanoballs, nanoflowers, nanorods, nanocontainers, nanobelts,
      nanocages, nanodiscs, nanodots, nanoprisms, nanoplates, nanorings, nanocubes,
      nanobranches, nanospheres, nanorattles, nanostars, nanotrees, nanowires,
      nanowalls, nanodiamonds, nanosheets, layered nanostructures, quantum dots,
      mesoporous nanostructures etc. in the field of cancer therapy and imaging. This
      review further highlights brief information about use of radionuclide in cancer.
      Lastly, different nanoformulations that are available in the market or are under
      clinical trials for cancer therapy and imaging are discussed.

PMID- 24730302
TI  - The role of nanotechnology in prostate cancer theranostic applications.
AB  - Recent advancements in cancer nanotechnology have facilitated a better way to
      diagnosis and provide therapy for prostate cancer. Nanotechnology has the
      potential to battle tumors at the site, where the cancer begins. There is a need
      to improve the therapeutic availabilities and the effectiveness of conventional
      chemotherapeutic agents for prostate cancer. Many therapeutic NPs have been
      developed with nanotechnology that can specifically target and deliver variety of
      agents including chemo drugs to destruct the prostate cancer cells without
      causing any damage to the healthy cells. Theranostic NPs have been developed to
      specifically target the prostate cancer cells using targeting ligands and to
      release the anticancer agents in a controlled and time-dependent manner for
      cancer therapy in combination with assisted imaging to monitor the effectiveness
      of the therapy in real time. The natural products and surface-modified polymers
      and metallic NPs have evolved as promising nanomaterials for targeted prostate
      cancer treatment. This review focuses on the role of alternative medicine,
      polymeric and metallic and metal oxide NPs in prostate cancer theranostics.

PMID- 24730303
TI  - Advances in topical drug delivery system: micro to nanofibrous structures.
AB  - This paper is a review of the latest developments in the field of topical drug
      delivery via which the drug is directly applied onto the skin with high
      selectivity and efficiency. Advances in microfiber-based medical textiles such as
      sutures and wound dressings, especially those containing a drug or an
      antimicrobial agent, have been covered briefly. A special focus is on recent
      developments in the area of nanofibrous drug delivery systems, which have several
      advantages due to their large surface area to volume ratio, high porosity and
      flexibility. The electrospinning technique to produce nanofibers has also been
      discussed with reference to latest advances such as multiple needles, needleless
      and coaxial forms of electrospinning. The applications of nanofibers in different
      areas such as wound dressing, periodontal and anticancer treatment have also been
      discussed.

PMID- 24730304
TI  - Nano-sized drug delivery systems for lymphatic delivery.
AB  - The lymphatic system plays important roles for immune responses, spreading cancer
      cells or viruses and disseminating infections. Thus, targeting drugs, such as
      anticancer, immunotherapeutic and lymphoid contrast agents, to both tumors and
      the lymphatics, has several advantages such as reduced systemic side effects and
      increased efficacy. For these reasons, much interest has been focused on the
      nature of the lymphatics and various studies on the lymphatic delivery of drugs
      have been carried out. Because the lymphatics consist of a single layer
      endothelium and have higher permeability compared with that of blood capillaries,
      studies using nano-sized carriers have been performed. Polymeric nanoparticles,
      liposomes, and lipid-based vehicles have been adopted as lymphatic delivery
      carriers. This review will focus on the clinical use of such nano-sized carriers
      that have been developed for imaging and drug delivery to the lymphatic system.
      Lymphatic delivery of drugs, such as anticancer, immunotherapeutic and lymphoid
      contrast agents, using nano-sized carriers has much more improved ability
      compared with that of conventional dosage forms, but it has not shown the
      specific lymphatic targeting ability yet. Finally, the challenges for the future
      are suggested in terms of the mechanisms governing the lymphatic delivery of nano
      sized carriers.

PMID- 24730305
TI  - Applications of nanoparticles for DNA based rabies vaccine.
AB  - Rabies is a fatal encephalomyelitis. Most cases occur in developing countries and
      are transmitted by dogs. The cell culture vaccines as associated with high cost;
      therefore, have not replaced the unsafe brain-derived vaccines. In the developing
      countries these brain-derived rabies vaccines still can be seen in action.
      Moreover, there will be a need for vaccines against rabies-related viruses
      against which classical vaccines are not always effective. The worldwide
      incidence of rabies and the inability of currently used vaccination strategies to
      provide highly potent and cost-effective therapy indicate the need for alternate
      control strategies. DNA vaccines have emerged as the safest vaccines and best
      remedy for complicated diseases like hepatitis, HIV, and rabies. A number of
      recombinant DNA vaccines are now being developed against several diseases such as
      AIDS and malaria. Therefore, it can be a valuable alternative for the production
      of cheaper rabies vaccines against its larger spectrum of viruses. In this review
      we report published data on DNA-based immunization with sequences encoding rabies
      with special reference to nanotechnology.

PMID- 24730307
TI  - Nanosensors for food safety.
AB  - This review summarizes recent research and development of nanosensors applied to
      the food safety. Since the food safety is directly related to the people's health
      and life, the food detection has received considerable attentions. However, this
      food security has emerged in China as a severe problem in recent years. Food
      safety problems frequently compromised due to formaldehyde, poison vegetables,
      excessive pesticide residues, etc. These kinds of food contaminations could not
      be detected efficiently by traditional methods. Applying nanotechnology and
      nanominerals, various food contaminations can be identified accurately. Therefore
      nanosensors have been widely used in the food detection. We introduce current
      research on nanosensors followed by the industrial application of nanosensors.
      Finally, the challenges for the future food safety using nanosensors are
      discussed.

PMID- 24730306
TI  - Doxorubicin nanoconjugates.
AB  - Doxorubicin is one of the most widely administered drugs for treatment of cancer.
      The shortcomings commonly encountered with this drug are severe cardiotoxicity,
      narrow therapeutic indices, and the development of multiple drug resistance.
      Hence, several nanoparticulate drug delivery systems have been designed to
      overcome these limitations and to improvise the overall therapeutic efficacy of
      doxorubicin. This review outlines the doxorubicin delivery systems, viz., metals
      and metal oxide nanoparticles, carbon nanotubes, liposomes, nanoparticles of
      solid lipid materials, lipid microemulsions, polymer-based nanoparticles, protein
      attached nanoparticles, polysaccharide nanoparticles, functional polymers, and
      nanoparticles of virus.

PMID- 24730308
TI  - Applications of nanomedicine in breast cancer detection, imaging, and therapy.
AB  - Worldwide, breast cancer remains as one of the most common cancer diagnosis and
      cause of cancer related death among women. Fortunately, nanomedicine has brought
      forth new potential and hope in breast cancer research. The extremely small size
      of nanoparticles makes it advantageous and potentially superior to use in tumor
      detection and imaging. One of the more extensively studied particles is quantum
      dots, semiconductor crystals which are capable of enhanced labeling and imaging
      of cancer cells. In addition, due to serious toxicity of chemotherapeutic agents,
      nano-formulations of breast cancer chemotherapy are under investigation and
      development. This may provide easier administering route and reduced frequency of
      drugs. With the use of nanoparticles, drug delivery can be carried out in a
      minimally invasive fashion and treatment regimens can be made much more targeted
      and specific for each patient. In this review article, we provide an overview on
      the role nanomedicine has played in breast cancer and mention some of the latest
      diagnostic and treatment modalities researched to date.

PMID- 24730309
TI  - Applications of scanning probe-atomic force microscopy in nanobioelectronics.
AB  - Scanning probe microscopy (SPM) is considered one of the most powerful tools for
      nanoscale studies that are becoming increasingly important, and SPM has shown
      rapid development. Atomic force microscopy (AFM), in particular, is the widely
      used SPM system. SPM, and especially AFM, has been used as a new measuring tool
      for phenomena that were earlier difficult to prove because of the limitations of
      earlier systems. In addition SPM allows acquiring nanoscale resolution images of
      the surface of materials. New applications are constantly being developed for
      SPM, and it is now used actively in material sciences and biological fields. The
      most important reason why SPM has attracted attention in the biological field is
      because it can be used in liquids as well. This allows the study of live cells
      and various other systems in nanoscale. Recently, there have been many advances
      in nanoscale studies, such as studies of cell interactions, cell changes
      according to environmental changes, and development of biosensors. This review is
      focused on applications in nanodevices, as well as on specific biological
      applications to discuss the development and opportunities of SPM in the
      biological field.

PMID- 24730310
TI  - Applications of nanotechnology in gastric cancer: detection and prevention by
      nutrition.
AB  - New and emerging technologies, such as nanotechnology, have the potential to
      advance nutrition science by assisting in the discovery, development, and
      delivery of several intervention strategies to improve health and reduce the risk
      and complications of several diseases, including gastric cancer. This article
      reviews gastric cancer in relation to nutrition, discussing gastric
      carcinogenesis in-depth in relation to prevention of the disease by nutrition, as
      well as current detection approaches using nanotechnology. The current status of
      molecular nutritional biomarkers for gastric cancer is also discussed, as well as
      future strategies for the tailored management of gastric cancer.

PMID- 24730311
TI  - Nanoparticles as antimicrobial agents: their toxicity and mechanisms of action.
AB  - Bacterial strains that are resistant to current antibiotics have become serious
      public health problems that increase the need to develop new bactericidal
      materials. Therefore, nanoparticles have gained importance in the field of
      chemotherapy. This review is focused on the unique properties of nanoparticles
      and their mechanism of action as antibacterial agents. The activities of
      nanoparticles on drug-resistant bacteria and risks of using them as antibacterial
      agents also have been documented.

PMID- 24730312
TI  - Nanoparticle-dependent labeling of mesenchymal stem cell.
AB  - Mesenchymal stem cells (MSCs) are able to differentiate into osteoblasts,
      adipocytes and chondroblasts. They hold great promise for tissue regeneration and
      treatment of immune-related diseases. Efficient application of MSCs requires safe
      cell tracking to follow stem cell fate over time in the host environment after
      infusion. This review discusses the nanoparticle-mediated MSC labeling, with
      special emphasis on the influence of nanoparticles on MSC bioactivities. We
      emphasize the importance of establishing guidelines, protocols and standards for
      labeling of MSCs in future clinical trials, so that MSCs can become a therapeutic
      agent with a reliable safety.

PMID- 24730313
TI  - Mesenchymal stem cell therapy for neurodegenerative diseases.
AB  - This paper reviews the recent studies and development of mesenchymal stem cell
      (MSCs) therapy for neurodegenerative diseases. MSCs transplantation, a promising
      therapy, can promote functional recovery by producing trophic factors that induce
      survival and regeneration of host neurons in animal models and patients with
      neurodegenerative diseases. In this review, we introduce briefly the potential
      benefits of MSCs. Finally, the possibility of clinical application in
      neurodegenerative diseases is also discussed.

PMID- 24730314
TI  - Stem cell therapy for ischemic stroke.
AB  - This paper reviews the recent studies and development of stem cell therapy for
      ischemic stroke. Stem cells can differentiate into several types of mature cells,
      including neurons and glial cells. Stem cell transplantation, a promising
      therapy, can be able to facilitate functional recovery both in animal models and
      stroke patients. In this review, we introduce briefly the different types of
      endogenous stem cells and the transplantation of exogenous stem cells; in
      addition, we discuss the timing, dosage, route, and tracing of stem cell therapy
      for ischemic stroke in details. Finally, the clinical challenge and application
      of stem cells in future are also discussed.

PMID- 24730315
TI  - Novel pH-sensitive biodegradable polymeric drug delivery systems based on ketal
      polymers.
AB  - This article reviews the recent developments on novel pH-sensitive ketal-based
      biodegradable polymeric drug delivery systems. Due to the degradation of ketal
      derivatives, neutral alcohols and ketones, ketal derivatives can be used to
      fabricate pH-degradable polymer with pH-degradable ketal linkages in new drug
      delivery systems by avoiding inflammatory problems. Due to the novelty of ketal
      polymers, there were few reports about ketal polymers. The review starts with a
      brief introduction to the pH-sensitive drug delivery system, followed by the
      structure, preparation and characterization techniques of ketal polymers.
      Thereafter, the promising applications in various diseases in relation to
      micro/nano drug carriers based on ketal polymers are summarized and discussed.

PMID- 24730316
TI  - Physiologically important metal nanoparticles and their toxicity.
AB  - Nanotechnology has been setting benchmarks for the last two decades, but the
      origins of this technology reach back to ancient history. Today, nanoparticles of
      both metallic and non-metallic origin are under research and development for
      applications in various fields of biology/therapeutics. Physiologically important
      metals are of concern because they are compatible with the human system in terms
      of absorption, assimilation, excretion, and side effects. There are several
      physiologically inorganic metals that are present in the human body with a wide
      range of biological activities. Some of these metals are magnesium, chromium,
      manganese, iron, cobalt, copper, zinc, selenium and molybdenum. These metals are
      synthesized in the form of nanoparticles by different physical and chemical
      methods. Physiologically important nanoparticles are currently under
      investigation for their bio-medical applications as well as for therapeutics.
      Along with the applicative aspects of nanoparticles, another domain that is of
      great concern is the risk assessment of these nanoparticles to avoid unnecessary
      hazards. It has been seen that these nanoparticles have been shown to possess
      toxicity in biological systems. Conventional physical and chemical methods of
      metal nanoparticle synthesis may be one possible reason for nanoparticle toxicity
      that can be overcome by synthesis of nanoparticles from biological sources. This
      review is an attempt to establish metal nanoparticles of physiological importance
      to be the best candidates for future nanotechnological tools and medicines, owing
      to the acceptability and safety in the human body. This can only be successful if
      these particles are synthesized with a better biocompatibility and low or no
      toxicity.

PMID- 24730317
TI  - Biological applications of nanobiotechnology.
AB  - Nanotechnology is a multidisciplinary field that covers a vast and diverse array
      of devices derived from engineering, physics, chemistry, and biology.
      Nanotechnology has opened up by rapid advances in science and technology,
      creating new opportunities for advances in the fields of medicine, electronics,
      foods, and the environment. Nanoscale structures and materials (nanoparticles,
      nanowires, nanofibers, nanotubes) have been explored in many biological
      applications (biosensing, biological separation, molecular imaging, anticancer
      therapy) because their novel properties and functions differ drastically from
      their bulk counterparts. Their high volume/surface ratio, improved solubility,
      and multifunctionality open many new possibilities. The objective of this review
      is to describe the potential benefits and impacts of the nanobiotechnology in
      different areas.

PMID- 24730318
TI  - [Everything stays different].

PMID- 24730319
TI  - [A varied congress program].

PMID- 24730320
TI  - [A positive, formative movement].

PMID- 24730321
TI  - [Hierarchical dominance in medicine].

PMID- 24730322
TI  - [The calm eye of the hurricane].

PMID- 24730324
TI  - [Change in the nursing scene].

PMID- 24730323
TI  - [Supporting instead of instructing].

PMID- 24730325
TI  - ["What do we do now?"].

PMID- 24730326
TI  - [How to avoid the abyss between theory and practice].

PMID- 24730327
TI  - [If worst comes to worst].

PMID- 24730328
TI  - [Increasing intellectual capital].

PMID- 24730329
TI  - [Effectiveness of situational e-learning by students in health care].

PMID- 24730330
TI  - [Leading a diverse team].

PMID- 24730331
TI  - ["For coworker satisfaction there is no patent prescription"].

PMID- 24730332
TI  - [In the 2nd World War anesthesia by nurses becomes established].

PMID- 24730333
TI  - [When blood vessels become constricted].

PMID- 24730334
TI  - [MDK wants it this way].

PMID- 24730335
TI  - [Researchers illuminate diabetes therapy].

PMID- 24730336
TI  - Computed tomography-histologic correlations in lung cancer.
AB  - The multidisciplinary approach is ideal in the management of patients with lung
      cancer. Multidisciplinary evaluation strengthens the differential diagnosis of
      aspecific radiological findings, indeed. Notably, the differential diagnosis of
      early stage lung cancer is a current challenge of CT imaging because the earlier
      the detection, the lower the accuracy of radiological features. This is
      particularly true for the most common subtype of lung cancer, adenocarcinoma,
      because it shows various radiological features. Such variety is also reflected by
      the 2011 classification of lung cancer, that likely affected the diagnostic
      agreement between radiologist and clinician. This review discusses the common
      issues of lung cancer diagnosis by paired radiological-histologic interpretation
      of CT findings.

PMID- 24730337
TI  - Tumours of the skin adnexa: a case series with focus on multiple segmental forms.
AB  - OBJECTIVE: Skin adnexal tumours (SAT) as a whole are rare tumours, and most of
      our current knowledge on SAT is from single case reports or small series focused
      on single histotypes. The purpose of this paper is to review a series of benign
      and malignant SAT diagnosed in a 20-year period. METHODS: All consecutive cases
      of SAT diagnosed between January 1992 and Dicember 2011 were retrieved. All
      slides were reviewed and diagnosed according to currently accepted criteria.
      RESULTS: 281 consecutive cases of SAT were found. The majority of cases (94.3%)
      were benign, the most frequent histotypes were eccrine spiradenoma, hidrocystoma,
      eccrine poroma, syringoma, sebaceous adenoma and trichofolliculoma. Benign SAT
      affected adult males more frequently (M/F = 153/112) (mean age 59 years).
      Recurrences were rare (2/265). Three cases of multiple segmental spiroadenoma
      were observed. Malignant SAT consituted only 5.7% of all cases comprising
      sebaceous carcinoma, extramammary Paget disease and apocrine carcinoma. There was
      a slight female predilection (M/F = 7/9) (mean age 72 years), although patients
      were older than those affected by benign SAT. All neoplasms were small and no
      recurrences were recorded. CONCLUSION: SAT are rare and most frequently benign.
      Correct diagnosis and complete surgical removal are important.

PMID- 24730338
TI  - Role of on-site microscopic evaluation of kidney biopsy for adequacy and
      allocation of glomeruli: comparison of renal biopsies with and without on-site
      microscopic evaluation.
AB  - Evaluation of kidney core biopsies ideally begins with on-site microscopic
      examination for adequacy and allocation of tissue for light microscopy (LM),
      immunofluorescence (IF) and electron microscopy (EM). However, some renal
      biopsies are not microscopically evaluated by a pathologist at the time of
      procedure, and are allocated without on-site evaluation. This study compares the
      actual outcome of these two techniques. We reviewed the reports of patients who
      underwent kidney biopsy for medical causes in the past two years. Eighty-eight
      biopsies had on-site microscopic evaluation by pathologists, and 70 biopsies did
      not undergo on-site evaluation. For biopsies without on-site evaluation, no
      glomeruli were seen in 5 (7.14%) cases for LM, 11 (15.71%) cases for IF and 6
      (8.57%) cases for EM. In cases with on-site evaluation, the absence of glomeruli
      was identified in 1 (1.13%) case for LM, 3 (3.4%) for IF and 3 (3.4%) for EM. The
      biopsies with on-site microscopic evaluation had 5.68% of the cases considered as
      inadequate, while 22% of biopsies without on-site evaluation were considered
      inadequate. The biopsies with on-site evaluation tended to have more glomeruli
      obtained during the procedure (p < 0.0005). Without on-site evaluation, the
      likelihood of getting an inadequate specimen compared to on-site evaluation is
      nearly four times greater.

PMID- 24730339
TI  - Adenocarcinoma arising in a tailgut cyst: a case report.
AB  - Tailgut cyst (TGC), also called retrorectal hamartoma, is a rare congenital
      lesion arising from persistent remnants of the postanal gut. Malignant
      transformation of TGC is exceedingly uncommon. We report herein the
      clinicopathologic features and the follow-up of a new case of a TGC with
      adenocarcinomatous transformation occurring in a 61 year-old woman.

PMID- 24730340
TI  - Breast cholesterol granuloma: a report of two cases with discussion on potential
      pathogenesis.
AB  - Breast cholesterol granuloma is a very rare lesion that can clinically and
      radiologically mimic breast carcinoma. Herein, we report two cases of breast
      cholesterol granulomas along with clinical, radiological, cytological and
      histological findings. We also discuss the potential pathogenesis of this rare
      breast nodular lesion, suggesting its relation not only to mammary duct ectasia
      but also to the rupture of a breast macrocyst.

PMID- 24730341
TI  - Synchronous occurrence of pulmonary adenocarcinoma and pleural diffuse malignant
      mesothelioma.
AB  - We report a rare case of diffuse malignant pleural mesothelioma synchronous with
      a localized adenocarcinoma of lung in a 68-year old man with a suspicious history
      of asbestos exposure. Computed tomography revealed a sub-pleural mass in the
      lower lobe and an irregular dense area of medium lobe of right lung with
      thickening of pleura encasing the lung parenchyma and homolateral pleural
      effusion 1 cm thick. The patient underwent surgery and a right medium and lower
      lobectomy was performed. Upon frozen sections, intraoperative diagnosis was
      adenocarcinoma with a poorly differentiated component of lung infiltrating the
      pleura. The postoperative histological definitive diagnosis with an important
      contribution of immunostaining was synchronous pulmonary adenocarcinoma and
      pleural diffuse malignant epithelioid mesothelioma.

PMID- 24730342
TI  - First case of hydatic cyst presenting as breast lump in a male patient.

PMID- 24730343
TI  - [Current status and perspective of vasculitis in Japan].

PMID- 24730344
TI  - [Overview of the 2012 Revised International Chapel Hill Consensus Conference
      Nomenclature of Vasculitides (CHCC2012)].

PMID- 24730345
TI  - [Epidemiology and classification of vasculitis-international comparative study
      and latest international trend].

PMID- 24730346
TI  - [Pathology of vasculitis].

PMID- 24730347
TI  - [Pathophysiology of medium-and small vessel vasculitis].

PMID- 24730348
TI  - [Therapy and prognosis of medium and small vessel vasculitis].

PMID- 24730349
TI  - [NETs in pathogenesis of vasculitis].

PMID- 24730350
TI  - [Disease susceptibility of vasculitis syndrome].

PMID- 24730351
TI  - [Awareness about and educational intervention for chronic kidney disease in the
      general population: from a survey of participants at the CKD educational lecture
      in Miyagi prefecture].
AB  - BACKGROUND: The prevalence of chronic kidney disease (CKD) and its complications,
      such as cardiovascular disease (CVD), cerebral vascular disease and end-stage
      kidney disease (ESKD), has been increasingly recognized as a global health
      problem in Japan. OBJECTIVE: We surveyed the awareness about CKD among medical
      professionals and the general public in Miyagi Prefecture. Additionally, we
      considered ways to lower the prevalence of CKD, CVD and ESKD. METHOD: We offered
      an annual educational lecture on CKD for the general population in Miyagi
      prefecture from 2010 to 2012. At each lecture, we distributed an anonymous survey
      to the participants about CKD and its complications. RESULTS: The number of
      survey respondents was 355, and their mean age was 63.9 years. Awareness about
      CKD among the participants, excluding medical professionals, was 58.0 %. Terms
      such as "serum creatinine" and "estimated GFR" were recognized in only about 60%
      and 40% of the respondents, respectively. Knowledge of risk factors for CKD, such
      as "elderly person" and "smoker," was at a low level. Furthermore, anemia and
      osteoporosis were not well-recognized as comorbidities of CKD. CONCLUSION: We
      found that the participants at the CKD educational lectures had limited knowledge
      about CKD and its complications; therefore, educational intervention regarding
      CKD, CVD and ESKD should be continued. Public awareness about CKD must be
      addressed to reduce CVD not only to prevent ESKD. The educational intervention
      will require a wide range of specialists in CKD care, general physicians, health
      nurses, and nutritionists, who contribute to community-based health care.

PMID- 24730352
TI  - [Rare case of systemic lupus erythematosus with encapsulating peritoneal
      sclerosis during hemodialysis].
AB  - A 57-year old male patient was admitted to our hospital because of severe
      vomiting and abdominal pain with massive ascites. He had been diagnosed as mixed
      connective tissue disease in 1997 and lupus nephritis ISN III (A/C) + V in 2003.
      Treatment was started with intravenous steroid pulse therapy combined with an
      immunosuppressant resulting in improvement of his proteinuria and serological
      activity. In 2008, the disease activity flared and he was admitted to our
      hospital with nephrotic syndrome. Hemodialysis was unavoidable, despite treatment
      with intravenous steroid pulse therapy and plasma exchange. We continued to treat
      him with oral prednisolone and tacrolimus. However, for personal reasons, he
      terminated tacrolimus treatment and massive ascites remained because of
      insufficient hemodialysis. Since the end of 2011, he suffered repeated abdominal
      pain with ileus and encapsulating peritoneal sclerosis (EPS) was detected. In
      February 2013, he underwent synechotomy for EPS. Here, we present a rare case of
      EPS in a hemodialysis patient.

PMID- 24730353
TI  - Construction of a clinical decision support system for undergoing surgery based
      on domain ontology and rules reasoning.
AB  - OBJECTIVE: To construct a clinical decision support system (CDSS) for undergoing
      surgery based on domain ontology and rules reasoning in the setting of
      hospitalized diabetic patients. MATERIALS AND METHODS: The ontology was created
      with a modified ontology development method, including specification and
      conceptualization, formalization, implementation, and evaluation and maintenance.
      The Protege-Web Ontology Language editor was used to implement the ontology.
      Embedded clinical knowledge was elicited to complement the domain ontology with
      formal concept analysis. The decision rules were translated into JENA format,
      which JENA can use to infer recommendations based on patient clinical situations.
      RESULTS: The ontology includes 31 classes and 13 properties, plus 38 JENA rules
      that were built to generate recommendations. The evaluation studies confirmed the
      correctness of the ontology, acceptance of recommendations, satisfaction with the
      system, and usefulness of the ontology for glycemic management of diabetic
      patients undergoing surgery, especially for domain experts. CONCLUSIONS: The
      contribution of this research is to set up an evidence-based hybrid ontology and
      an evaluation method for CDSS. The system can help clinicians to achieve
      inpatient glycemic control in diabetic patients undergoing surgery while avoiding
      hypoglycemia.

PMID- 24730354
TI  - Aerobic plus resistance training was more effective in improving the visceral
      adiposity, metabolic profile and inflammatory markers than aerobic training in
      obese adolescents.
AB  - The purpose of this study was to determine whether aerobic plus resistance
      training (AT + RT) is more effective than aerobic training (AT) at reducing
      inflammatory markers and cardiovascular risk in obese adolescents. A total of 139
      obese adolescents were enrolled, aged 15-19 years, body mass index (BMI) >= 95th
      percentile and participated in 1 year of interdisciplinary intervention. They
      were randomised into two groups: AT (n = 55), AT + RT (n = 61). Blood samples
      were collected to analyse glycaemia, insulin, the lipid profile, leptin and
      adiponectin concentrations. Insulin resistance was measured by homeostasis model
      assessment of insulin resistance index (HOMA-IR). The AT + RT group showed better
      results with regard to decreased body fat mass, low-density lipoprotein
      concentration (LDL-c) levels, subcutaneous and visceral fat and increased body
      lean mass. Indeed, a reduction of hyperleptinaemia and an increase in adiponectin
      concentrations, promoting an improvement in the leptin/adiponectin ratio, was
      observed. Important clinical parameters were improved in both types of exercise;
      however, AT + RT was more effective in improving the visceral adiposity,
      metabolic profile and inflammatory markers than AT alone, suggesting clinical
      applications for the control of intra-abdominal obesity and cardiovascular risk
      in the paediatric population.

PMID- 24730355
TI  - QM/MM free-energy simulations of reaction in Serratia marcescens Chitinase B
      reveal the protonation state of Asp142 and the critical role of Tyr214.
AB  - Serratia marcescens Chitinase B (ChiB), belonging to the glycosidase family 18
      (GH18), catalyzes the hydrolysis of beta-1,4-glycosidic bond, with retention of
      configuration, via an unusual substrate-assisted mechanism, in which the
      substrate itself acts as an intramolecular nucleophile. Here, both elementary
      steps (glycosylation and deglycosylation) of the ChiB-catalyzed reaction are
      investigated by means of combined quantum mechanics/molecular mechanics (QM/MM)
      umbrella sampling molecular dynamics (MD) simulations at the SCC-DFTB/CHARMM22
      level of theory. We examine the influence of the Asp142 protonation state on the
      reaction and the role that this residue performs in the reaction. Our simulations
      show that reaction with a neutral Asp142 is preferred and demonstrate that this
      residue provides electrostatic stabilization of the oxazolinium ion intermediate
      formed in the reaction. Insight into the conformational itinerary ((1,4)B<
      >(4)H5<->(4)C1) adopted by the substrate (bound in subsite -1) along the
      preferred reaction pathway is also provided by the simulations. The relative
      energies of the stationary points found along the reaction pathway calculated
      with SCC-DFTB and B3LYP were compared. The results suggest that SCC-DFTB is an
      accurate method for estimating the relative barriers for both steps of the
      reaction; however, it was found to overestimate the relative energy of an
      intermediate formed in the reaction when compared with the higher level of
      theory. Glycosylation is suggested to be a rate-determining step in the reaction
      with calculated overall reaction free-energy barrier of 20.5 kcal/mol, in a
      reasonable agreement with the 16.1 kcal/mol barrier derived from the experiment.
      The role of Tyr214 in catalysis was also investigated with the results,
      indicating that the residue plays a critical role in the deglycosylation step of
      the reaction. Simulations of the enzyme-product complex were also performed with
      an unbinding event suggested to have been observed, affording potential new
      mechanistic insight into the release of the product of ChiB.

PMID- 24730356
TI  - Urological chronic pelvic pain syndrome symptom flares: characterisation of the
      full range of flares at two sites in the Multidisciplinary Approach to the Study
      of Chronic Pelvic Pain (MAPP) Research Network.
AB  - OBJECTIVES: To describe the full range of symptom exacerbations defined by people
      with interstitial cystitis/bladder pain syndrome and chronic prostatitis/chronic
      pelvic pain syndrome as 'flares', and to investigate their associated healthcare
      utilization and bother at two sites of the Multidisciplinary Approach to the
      Study of Chronic Pelvic Pain (MAPP) Epidemiology and Phenotyping study. SUBJECTS
      AND METHODS: Participants completed a flare survey that asked them: 1) whether
      they had ever had flares ('symptoms that are much worse than usual') that lasted
      <1 h, >1 h and <1 day, and >1 day; and 2) for each duration of flare, to report:
      their average length and frequency; their typical levels of urological and pelvic
      pain symptoms; and their levels of healthcare utilization and bother. We compared
      participants' responses to their non-flare MAPP values and by duration of flare
      using generalized linear mixed models. RESULTS: Of 85 participants, 76 (89.4%)
      completed the flare survey, 72 (94.7%) of whom reported experiencing flares.
      Flares varied widely in terms of their duration (seconds to months), frequency
      (several times per day to once per year or less), and intensity and type of
      symptoms (e.g. pelvic pain vs urological symptoms). Flares of all durations were
      associated with greater pelvic pain, urological symptoms, disruption to
      participants' activities and bother, with increasing severity of each of these
      factors as the duration of flares increased. Days-long flares were also
      associated with greater healthcare utilization. In addition to duration, symptoms
      (pelvic pain, in particular) were also significant determinants of flare-related
      bother. CONCLUSIONS: Our findings suggest that flares are common and associated
      with greater symptoms, healthcare utilization, disruption and bother. Our
      findings also show the characteristics of flares most bothersome to patients
      (i.e. increased pelvic pain and duration), and thus of greatest importance to
      consider in future research on flare prevention and treatment.

PMID- 24730357
TI  - Long-term effects of a universal family intervention: mediation through parent
      adolescent conflict.
AB  - This randomized trial of a family-focused preventive intervention for Mexican
      American middle schoolers examined internalizing, externalizing, and substance
      use outcomes in late adolescence, 5 years after completing the intervention.
      Parent-adolescent conflict was tested as a mediator of these effects. The role of
      parent and adolescent acculturation in these pathways was also examined. There
      were 494 seventh-grade adolescents and their primary female caregivers randomized
      to receive either a 9-week multicomponent intervention or a brief workshop
      control group. Assessments were conducted at pretest, 2-year follow-up (9th
      grade), and 5-year follow-up (when most participants were in the 12th grade). The
      Bridges program significantly reduced mother-adolescent conflict measured in the
      9th grade, with conflict mediating program effects on internalizing and
      externalizing symptoms, adolescent substance use, and diagnosed internalizing
      disorder in late adolescence. Mother and child acculturation were both
      significantly predictive of late adolescence outcomes. Contrary to hypotheses,
      neither mother nor child acculturation emerged as a significant predictor of
      mother-adolescent conflict, and the interaction of mother and adolescent
      acculturation was similarly not related to mother-adolescent conflict.
      Intervention effects were largely consistent across different levels of
      acculturation. These findings provide support for the efficacy of family-focused
      intervention during early adolescence, both in reducing mental health problems
      and substance use in the long term and in impacting parent-adolescent conflict
      processes that appear to play an important role in the development of later
      adjustment problems. 

PMID- 24730359
TI  - Prevalence and severity of hepatopulmonary syndrome and its influence on survival
      in cirrhotic patients evaluated for liver transplantation.
AB  - The prevalence of hepatopulmonary syndrome (HPS) and its influence on survival
      before and after liver transplantation (LT) remain controversial. Additionally,
      the chronology of post-LT reversibility is unclear. This study prospectively
      analyzed 316 patients with cirrhosis who were evaluated for LT in 2002-2007; 177
      underwent LT at a single reference hospital. HPS was defined by a partial
      pressure of arterial oxygen (PaO2 ) <70 mmHg and/or an alveolar-arterial oxygen
      gradient (A-a PO2 ) >=20 mmHg in the supine position and positive contrast
      echocardiography. The prevalence of HPS was 25.6% (81/316 patients), and most
      patients (92.6%) had mild or moderate HPS. High Child-Pugh scores and the
      presence of ascites were independently associated with HPS. Patients with and
      without HPS did not significantly differ in LT waiting list survival (mean 34.6
      months vs. 41.6 months, respectively; log-rank, p = 0.13) or post-LT survival
      (mean 45 months vs. 47.6 months, respectively; log-rank, p = 0.62). HPS was
      reversed in all cases within 1 year after LT. One-fourth of the patients with
      cirrhosis who were evaluated for LT had HPS (mostly mild to moderate); the
      presence of HPS did not affect LT waiting list survival. HPS was always reversed
      after LT, and patient prognosis did not worsen.

PMID- 24730360
TI  - Near-infrared-light-based nano-platform boosts endosomal escape and controls gene
      knockdown in vivo.
AB  - Current nanoparticle-based gene delivery techniques face two major limitations,
      namely, endosomal degradation and poor cytosolic release of the nanoparticles and
      nonspecificity of treatment. These limitations can be overcome with certain light
      based techniques, such as photochemical internalization to enable endosomal
      escape of the delivered nanoparticles and light-controlled gene expression to
      overcome the nonspecific effects. However, these techniques require UV/visible
      light, which is either phototoxic and/or has low tissue penetration capabilities,
      thus preventing their use in deep tissues in a clinical setting. In an effort to
      overcome these barriers, we have successfully demonstrated a light-based gene
      delivery system that significantly boosts cytosolic gene delivery, with precise
      control over gene expression and the potential for use in nonsuperficial tissues.
      Core-shell fluorescent upconversion nanoparticles excited by highly penetrating
      near-infrared radiation and emitting simultaneously in the ultraviolet and
      visible ranges were synthesized and used as remote nanotransducers to
      simultaneously activate endosomal escape and gene knockdown. Gene knockdown using
      photomorpholinos was enhanced as much as 30% in vitro compared to the control
      without endosomal escape facilitation. A similar trend was seen in vivo in a
      murine melanoma model, demonstrating the enormous clinical potential of this
      system. 

PMID- 24730358
TI  - HIV-1 vaginal transmission: cell-free or cell-associated virus?
AB  - The vast majority of new HIV infections in male-to-female transmission occurs
      through semen, where HIV-1 is present in two different forms: as free and as cell
      associated virus. In the female lower genital tract, semen mixes with female
      genital secretions that contain various factors, some of which facilitate or
      inhibit HIV-1 transmission. Next, HIV-1 crosses the genital epithelia, reaches
      the regional lymph nodes, and disseminates through the female host. Cervico
      vaginal mucosa contains multiple barriers, resulting in a low probability of
      vaginal transmission. However, in some cases, HIV-1 is able to break these
      barriers. Although the exact mechanisms of how these barriers function remain
      unclear, their levels of efficiency against cell-free and cell-associated HIV-1
      are different, and both cell-free and cell-associated virions seem to use
      different strategies to overcome these barriers. Understanding the basic
      mechanisms of HIV-1 vaginal transmission is required for the development of new
      antiviral strategies to contain HIV-1 epidemics. 

PMID- 24730362
TI  - Remotely triggered geometrical isomerization of a binuclear complex.
AB  - Binuclear organometallic molecules are model systems for investigating
      intramolecular spin-coupling and charge-transfer processes. Using electrospray
      ionization, Fe(salten) dimers linked by dipyridyl disulfide are deposited on gold
      for probing with a low-temperature scanning tunneling microscope. Each monomer
      constitutes a multistable switch owing to its geometric isomerism. Controlled and
      reversible remote switching within a single dimer is demonstrated. The process is
      attributed to intramolecular electron transfer. 

PMID- 24730361
TI  - Oral sucrose and non-nutritive sucking goes some way to reducing pain during
      retinopathy of prematurity eye examinations.
AB  - AIM: To evaluate the efficacy of oral sucrose combined with non-nutritive sucking
      for reducing pain associated with retinopathy of prematurity screening. METHODS:
      This was a randomised controlled study of 64 infants undergoing eye examination
      for retinopathy of prematurity screening. Topical anaesthetic (Proparacaine;
      Alcaine((r)) drop 0.5%: ALCON CANADA Inc., Mississauga, Canada) was applied 30
      sec before the eye examination in all infants. The infants in intervention group
      (Group 1, n = 32) received 0.5 mL/kg of 24% sucrose with a pacifier. The control
      group (Group 2, n = 32) received 0.5 mL/kg of sterile water with a pacifier.
      RESULTS: The groups had similar gestational ages (28.5 +/- 2.8 weeks), mean
      birthweight (1304 +/- 466 g) or corrected gestational age (35.4 +/- 3.7 weeks) at
      examination. The intervention group had a significantly lower mean Premature
      Infant Pain Profile score during examination of the first eye, following
      insertion of the speculum (Group 1:13.7 +/- 2.1 vs. Group 2:16.4 +/- 1.8, p =
      0.001). CONCLUSION: Although sucrose combined with non-nutritive sucking modestly
      reduces pain scores during eye examinations, there is need to further studies to
      explore significant pain relief for infants undergoing retinopathy of prematurity
      screening.

PMID- 24730363
TI  - Evaluation of a novel strain of infectious bronchitis virus emerged as a result
      of spike gene recombination between two highly diverged parent strains.
AB  - The emergence of new variant strains of the poultry pathogen infectious
      bronchitis virus (IBV) is continually reported worldwide, owing to the labile
      nature of the large single-stranded RNA IBV genome. High resolution melt curve
      analysis previously detected a variant strain, N1/08, and the present study
      confirmed that this strain had emerged as a result of recombination between
      Australian subgroup 2 and 3 strains in the spike gene region, in a similar manner
      reported for turkey coronaviruses. The S1 gene for N1/08 had highest nucleotide
      similarity with subgroup 2 strains, which is interesting considering subgroup 2
      strains have not been detected since the early 1990s. SimPlot analysis of the 7.2
      kb 3' end of the N1/08 genome with the same region for other Australian reference
      strains identified the sites of recombination as immediately upstream and
      downstream of the S1 gene. A pathogenicity study in 2-week-old chickens found
      that N1/08 had similar pathogenicity for chicken respiratory tissues to that
      reported for subgroup 2 strains rather than subgroup 3 strains. The results of
      this study demonstrate that recombination is a mechanism utilized for the
      emergence of new strains of IBV, with the ability to alter strain pathogenicity
      in a single generation. 

PMID- 24730365
TI  - Adolescent personality: associations with Basal, awakening, and stress-induced
      cortisol responses.
AB  - The purpose of the present study was to investigate the associations between
      personality facets and hypothalamic-pituitary-adrenal (HPA) axis functioning.
      Previous studies have mainly focussed on stress-induced HPA-axis activation. We
      hypothesized that other characteristics of HPA-axis functioning would have a
      stronger association with personality based on the neuroendocrine literature.
      Data (n = 343) were used from the TRacking Adolescents' Individual Lives Survey
      (TRAILS), a large prospective cohort study of Dutch adolescents. We studied the
      association between facets of Neuroticism, Extraversion, and Conscientiousness
      and basal cortisol, the cortisol awakening response (CAR), and four measures of
      stress-induced HPA-axis activity. Basal cortisol levels were related to facets of
      all three personality traits. The CAR and stress-induced cortisol were not
      related to personality. Possibly due to its more trait-like nature, basal
      cortisol seems more informative than stress-induced cortisol when investigating
      trait-like characteristics such as personality facets. 

PMID- 24730366
TI  - Perfluoroalkyl-substituted thiophenes and pyrroles from donor-acceptor
      cyclopropanes and heterocumulenes: synthesis and exploration of their reactivity.
AB  - A methyl 2-trifluoromethyl-2-siloxycyclopropanecarboxylate was smoothly
      deprotonated by lithium diisopropylamide and reacted with carbon disulfide and
      methyl iodide to afford a dihydrothiophene derivative. The crucial step in this
      transformation is a ring-expansion of the anionic intermediate by [1,3]
      sigmatropic rearrangement. The dihydrothiophene was converted into the
      corresponding 5-trifluoromethylthiophene derivative by phosphoryl chloride in
      refluxing pyridine. A one-pot version of the reaction sequence efficiently
      provided the thiophene in good yield. Analogously, aryl- and alkyl-substituted
      isothiocyanates instead of carbon disulfide afforded the corresponding
      trifluoromethyl-substituted pyrroles in moderate to very good overall yields.
      Explorative reactivity studies with the methylthio-substituted thiophene and
      pyrrole derivatives demonstrate that they are precursors of a range of
      interesting trifluoromethyl-substituted products, including new members from the
      thienothiophene and thienopyrrole class. 

PMID- 24730367
TI  - Lost in the categorical shuffle: evidence for the social non-prototypicality of
      black women.
AB  - The white male norm hypothesis (Zarate & Smith, 1990) posits that White men's
      race and gender go overlooked as a result of their prototypical social statuses.
      In contrast, the intersectional invisibility hypothesis (Purdie-Vaughns & Eibach,
      2008) posits that people with membership in multiple subordinate social groups
      experience social invisibility as a result of their non-prototypical social
      statuses. The present research reconciles these contradictory theories and
      provides empirical support for the core assumption of the intersectional
      invisibility hypothesis-that intersectional targets are non-prototypical within
      their race and gender ingroups. In a speeded categorization task, participants
      were slower to associate Black women versus Black men with the category "Black"
      and slower to associate Black women versus White women with the category "woman."
      We discuss the implications of this work for social categorical theory
      development and future intersectionality research.

PMID- 24730369
TI  - Enhancing adhesion of elastomeric composites through facile patterning of surface
      discontinuities.
AB  - Patterning interfaces can provide enhanced adhesion over a projected area.
      However, careful consideration of the material properties and geometry must be
      applied to provide successful reversible adhesives. We present a simple method to
      use patterned, elastomeric fabric composites to enhance the shear adhesion
      strength by nearly 40% compared to a non-patterned sample. We describe how this
      enhancement depends on the pattern geometry, the velocity dependence of the
      adhesive materials, and the controlled displacement rate applied to the
      interface. Through these observations, we discuss strategies for improving
      reversible adhesives. 

PMID- 24730368
TI  - The efficacy of a Hansenula-derived 20 kDa pegylated interferon alpha-2a in the
      treatment of genotype 4 chronic hepatitis C.
AB  - Pending the emergence and approval of an effective interferon-free regimen,
      pegylated interferon will remain an integral part of the treatment of genotype 4
      hepatitis C virus (HCV). A new 20 kDa pegylated interferon has been developed in
      a cost-saving fungal-based system and is commercialized in Egypt at a quarter to
      a third of the price of conventional pegylated interferon. We hereby test the
      efficacy and safety of this novel cost-saving interferon. One hundred ninety
      three consecutive treatment-naive patients with genotype 4 HCV were treated using
      the following regimen: subcutaneous 20 kDa pegylated interferon 160 MUg once
      weekly plus oral ribavirin 1,000 or 1,200 mg daily (based on body weight <75 kg
      or >=75 kg, respectively) for 48 weeks. A sustained virological response (SVR) of
      51% was achieved. Interim responses included rapid virological response (RVR):
      54%, early virological response (EVR): 78% (complete EVR: 71%, partial EVR: 7%),
      and end of treatment response: 63%. The most common adverse events were flu-like
      symptoms, dyspepsia, anorexia, and pruritus. Treatment-related serious adverse
      events were encountered in only 2 patients (1%). Discontinuation of treatment due
      to adverse events occurred in only 13 patients (7%). Multiple logistic regression
      analyses revealed the following factors as predictors of SVR: RVR (P<0.001),
      alpha-fetoprotein<upper limit of normal (ULN) (P=0.007), and early biochemical
      response (alanine aminotransferase <ULN at week 12, P=0.018). Hansenula-derived
      20 kDa pegylated interferon alpha-2a is an effective and safe treatment for
      genotype 4 chronic HCV. These results highlight the presence of a less costly
      treatment for chronic HCV, pending the emergence of an effective inexpensive
      interferon-free regimen. A direct comparison with 40 kDa interferon remains
      essential to adequately compare the efficacy and safety.

PMID- 24730370
TI  - Smart technologies to enhance social connectedness in older people who live at
      home.
AB  - AIM: To examine the effectiveness of smart technologies in improving or
      maintaining the social connectedness of older people living at home. METHODS: We
      conducted a systematic review and critical evaluation of research articles
      published between 2000 and 2013. Article screening, data extraction and quality
      assessment (using the Downs and Black checklist) were conducted by two
      independent researchers. RESULTS: Eighteen publications were identified that
      evaluated the effect of smart technologies on dimensions of social connectedness.
      Fourteen studies reported positive outcomes in aspects such as social support,
      isolation and loneliness. There was emerging evidence that some technologies
      augmented the beneficial effects of more traditional aged-care services.
      CONCLUSION: Smart technologies, such as tailored internet programs, may help
      older people better manage and understand various health conditions, resulting in
      subsequent improvements in aspects of social connectedness. Further research is
      required regarding how technological innovations could be promoted, marketed and
      implemented to benefit older people.

PMID- 24730371
TI  - Heuristic for maximizing DNA reuse in synthetic DNA library assembly.
AB  - De novo DNA synthesis is in need of new ideas for increasing production rate and
      reducing cost. DNA reuse in combinatorial library construction is one such idea.
      Here, we describe an algorithm for planning multistage assembly of DNA libraries
      with shared intermediates that greedily attempts to maximize DNA reuse, and show
      both theoretically and empirically that it runs in linear time. We compare
      solution quality and algorithmic performance to the best results reported for
      computing DNA assembly graphs, finding that our algorithm achieves solutions of
      equivalent quality but with dramatically shorter running times and substantially
      improved scalability. We also show that the related computational problem bounded
      depth min-cost string production (BDMSP), which captures DNA library assembly
      operations with a simplified cost model, is NP-hard and APX-hard by reduction
      from vertex cover. The algorithm presented here provides solutions of near
      minimal stages and thanks to almost instantaneous planning of DNA libraries it
      can be used as a metric of "manufacturability" to guide DNA library design. Rapid
      planning remains applicable even for DNA library sizes vastly exceeding today's
      biochemical assembly methods, future-proofing our method.

PMID- 24730372
TI  - Cytologic findings from a benign giant cell tumor of the tendon sheath in a dog.
AB  - A 6-year-old male neutered Australian Shepherd dog was presented for evaluation
      of a subcutaneous mass on the plantar aspect of the proximal left metatarsus.
      Fine-needle aspirate smears contained numerous plump spindle cells and large
      multinucleated cells amongst a considerable amount of pink extracellular matrix.
      Histopathologic diagnosis of the tissue obtained during initial biopsy and
      eventual surgical cytoreduction of the mass was a benign giant cell tumor of the
      tendon sheath (GCTTS). Immunohistochemically, the synovioblastic neoplastic cells
      were diffusely strongly positive for vimentin and S-100, were multifocally
      moderately positive for cytokeratin AE1/3, and were negative for CD18, muscle
      specific actin (MSA), and melanoma-associated antigen (mutated) 1 (MUM-1). The
      dog recovered from surgery and underwent definitive radiation therapy to treat
      the local residual disease. Eight months later, the mass had not recurred. The
      diagnosis of GCTTS in this case supports previously published reports describing
      GCTTS as a relevant disease entity in dogs, and provides the first documentation
      of cytologic findings with this tumor. Further investigation is needed to
      correlate pathologic features with clinical behavior and response to therapy in
      dogs. 

PMID- 24730373
TI  - Prophylactic arterial embolization in high-risk peptic ulcer bleeding after
      endoscopic hemostasis is achieved: a new step.

PMID- 24730374
TI  - Role of PdxR in the activation of vitamin B6 biosynthesis in Listeria
      monocytogenes.
AB  - Listeria monocytogenes PdxR is a member of the poorly characterized but
      widespread group of MocR/GabR-type chimeric bacterial proteins that have DNA
      binding and aminotransferase-like domains. Using mutational analysis, real-time
      RT-PCR, transcriptional fusions, gel-shift assays, DNase I footprinting, and in
      vitro transcription, it was shown that PdxR is a direct activator of the pdxST
      operon, transcribed divergently from pdxR and responsible for the de novo
      synthesis of pyridoxal 5'-phosphate (PLP), the major active form of vitamin B6 .
      PLP acts as an anti-activator of PdxR and is the only effector required to reduce
      the activity of PdxR. PdxR is also a negative autoregulator, and its ability to
      repress is increased by PLP. A dyad-symmetry sequence, which overlaps the -35
      region of the pdxS promoter and lies downstream of the pdxR transcription start
      point, serves as an important element of the PdxR binding site. Unexpectedly,
      some mutations in this activator binding site, disrupting the dyad-symmetry
      element, caused constitutive, B6 -independent expression from the pdxS promoter.
      The data suggest that PdxR-like proteins, for which PLP plays just a signalling
      role, form a separate functional group among the MocR/GabR-type proteins.

PMID- 24730375
TI  - Cognitive impairment and memory loss associated with histoplasmosis: a case
      study.
AB  - Histoplasmosis is a rare disease caused by inhalation of the fungus Histoplasma
      capsulatum. It can spread via cerebral circulation to the central nervous system
      as a manifestation of a disseminated infection; particularly in patients with
      immune suppression, which can result in isolated ring-enhancing lesions and
      inflammation in the brain. Of the reported disseminated histoplasmosis cases
      (approximately 1 in 2000 per year), only 5-20% have evidence of central nervous
      system involvement. This paper reviews a single case study of a 57-year-old
      female diagnosed with disseminated CNS histoplasmosis. Patient's complaints
      included reduced short-term memory, word-finding problems, and difficulty
      organizing, making decisions, getting lost while driving, recalling names,
      retaining information while reading, and slowed processing speed. There was also
      a history of mild depression and anxiety. Direct testing revealed deficits in
      multiple cognitive domains including complex attention, processing speed,
      semantic fluency, visual scanning, motor speed, set-shifting, naming, nonverbal
      memory, and verbal memory. Neuropsychological deficits suggest cortical and
      subcortical brain dysfunction, including anterior, temporal, and mesial-temporal
      regions. This case illustrates the need for neuropsychologists to understand
      histoplasmosis, the related pathophysiology, and the neuropsychological impact;
      particularly with the potential for delayed progression. 

PMID- 24730376
TI  - Clinical review of Hendra virus infection in 11 horses in New South Wales,
      Australia.
AB  - CASE SERIES: Between 2006 and 2012, there were 11 horses diagnosed with Hendra
      virus (HeV) on 9 independent premises in New South Wales (NSW). We defined a case
      of HeV as premises where one or more horses were confirmed to be infected with
      HeV by PCR. All the cases occurred in the north-eastern region of NSW. In 8 of
      the 9 cases, infection occurred within 2 months over the winter of 2011. With no
      exception, the affected horses were kept at pasture on properties visited by
      flying foxes. Of the 11 horses testing positive for HeV, 5 had an association
      with a fence, with the horses dead or dying on a fence line. In the majority of
      cases, disease was an acute illness leading to death within 48 h. When signs of
      disease were observed, neurological signs predominated. There was limited spread
      to in-contact horses, with only two properties having more than one horse
      affected. There was significant variation in the sampling strategies undertaken
      by veterinarians. CONCLUSION: Caution is needed to interpret a negative diagnosis
      when only swabs have been collected.

PMID- 24730377
TI  - Efficacy of gallium maltolate against Lawsonia intracellularis infection in a
      rabbit model.
AB  - Antimicrobial efficacy against Lawsonia intracellularis is difficult to evaluate
      in vitro, thus, the effects of gallium maltolate's (GaM) were investigated in a
      rabbit model for equine proliferative enteropathy (EPE). Juvenile (5-6-week-old)
      does were infected with 3.0 * 10(8) L. intracellularis/rabbit and allocated into
      three groups (n = 8). One week postinfection, one group was treated with GaM, 50
      mg/kg; one, with doxycycline, 5 mg/kg; and one with a sham-treatment (control).
      Feces and blood were collected daily and weekly, respectively, to verify presence
      of L. intracellularis fecal shedding using qPCR, and seroconversion using
      immunoperoxidase monolayer assay. Rabbits were sacrificed after 1 week of
      treatment to collect intestinal tissues focusing on EPE-affected sections.
      Intestinal lesions were confirmed via immunohistochemistry. No difference was
      noted between treatments regarding EPE-lesions in jejunum (P = 0.51), ileum (P =
      0.74), and cecum (P = 0.35), or in L. intracellularis fecal shedding (P = 0.64).
      GaM and doxycycline appear to have similar efficacy against EPE in infected
      rabbits. 

PMID- 24730378
TI  - Does perceived racial discrimination predict changes in psychological distress
      and substance use over time? An examination among Black emerging adults.
AB  - We assessed whether perceived discrimination predicted changes in psychological
      distress and substance use over time and whether psychological distress and
      substance use predicted change in perceived discrimination over time. We also
      assessed whether associations between these constructs varied by gender. Our
      sample included 607 Black emerging adults (53% female) followed for 4 years.
      Participants reported the frequency with which they had experienced racial
      hassles during the past year, symptoms of anxiety and depression during the past
      week, and cigarette and alcohol use during the past 30 days. We estimated a
      series of latent growth models to test our study hypotheses. We found that the
      intercept of perceived discrimination predicted the linear slopes of anxiety
      symptoms, depressive symptoms, and alcohol use. We did not find any associations
      between the intercept factors of our mental health or substance use variables and
      the perceived discrimination linear slope factor. We found limited differences
      across paths by gender. Our findings suggest a temporal ordering in the
      associations among perceived racial discrimination, psychological distress, and
      alcohol use over time among emerging adults. Further, our findings suggest that
      perceived racial discrimination may be similarly harmful among men and women.

PMID- 24730379
TI  - Eavesdropping on the family: a pilot investigation of corporal punishment in the
      home.
AB  - This study tested the feasibility of using audio recorders to collect novel
      information about family interactions. Research into corporal punishment (CP) has
      relied, almost exclusively, on self-report data; audio recordings have the
      promise of revealing new insights into the use and immediate consequences of CP.
      So we could hear how parents respond to child conflicts, 33 mothers wore digital
      audio recorders for up to 6 evenings. We identified a total of 41 CP incidents,
      in 15 families and involving 22 parent-child dyads. These incidents were
      evaluated on 6 guidelines culled from the writings of CP advocates. The results
      indicated, contrary to advice, CP was not being used in line with 3 of the 6
      recommendations and for 2 others, the results were equivocal. The last
      recommendation could not be assessed with audio. Latency analyses revealed
      children, after being hit, were misbehaving again within 10 minutes after 73% of
      the incidents. Mothers' self reports about whether they used CP were found to
      correspond to the audio data in 81% of the cases. Among the mothers who were
      hitting, CP occurred at a much higher rate than the literature indicates. These
      results should be viewed as preliminary because of the small sample of families
      and the even smaller number of families who used CP. Nevertheless, this pilot
      study demonstrates that audio recording naturally occurring momentary processes
      in the family is a viable method for collecting new data to address important
      questions about family interactions.

PMID- 24730380
TI  - Cancer conversations in context: naturalistic observation of couples coping with
      breast cancer.
AB  - This study explored the feasibility and potentials of a naturalistic observation
      approach to studying dyadic coping in everyday life. Specifically, it examined
      the natural context and content of the spontaneous cancer conversations of
      couples coping with cancer, and how they relate to patients' and spouses'
      psychological adjustment. Women with breast cancer (N = 56) and their spouses
      wore the electronically activated recorder (EAR), an unobtrusive observation
      method that periodically records snippets of ambient sounds, over one weekend to
      observe the couples' cancer conversations in their natural context. Both patients
      and spouses completed self-reported measures of psychological adjustment at
      baseline and at a 2-month follow-up. Cancer was a topic of approximately 5% of
      couples' conversations. Cancer conversations occurred more often within the
      couple than with friends and family, and they were more often informational than
      emotional or supportive. Consistent with research on the social cognitive
      processing model (Lepore & Revenson, 2007), spouses' engagement in emotional
      disclosure and informational conversation with patients predicted better patient
      adjustment. This first naturalistic observation study of dyadic coping revealed
      that the EAR method can be implemented with high compliance and relatively low
      obtrusiveness within the sensitive context of couples coping with cancer, and
      having a spouse who discussed cancer in an emotional or informational way
      predicted better patient adjustment. As a complement to in-lab and other
      momentary assessment methods, a naturalistic observation approach with a method
      such as the EAR can contribute to a more comprehensive understanding of the role
      that communication processes play in coping with cancer.

PMID- 24730382
TI  - Glaucomics: a call for systems diagnostics for 21(st) century ophthalmology and
      personalized visual health.
AB  - This article analyzes and theorizes the current knowledge silos at the
      intersection of omics science, ophthalmology, personalized medicine, and global
      visual health. Visual disorders represent one of the largest health care
      expenditures in the United States, costing $139 billion per year. In middle
      income and industrialized countries, glaucoma is a World Health Organization
      priority category eye disease, known for difficulties in its early diagnosis,
      chronic progressive nature, and large person-to-person differences in drug
      efficacy and safety. A complex disease, glaucoma is best conceptualized as a
      syndrome displaying an ostensibly common clinical end-point, but with vastly
      heterogeneous molecular underpinnings and host-environment interactions. About
      12% of all global blindness is attributable to glaucoma. Glaucomics is a term
      that we coin here so as to introduce omics science and systems diagnostics to
      ophthalmology, a field that can benefit enormously from personalized medicine,
      and which has sadly lagged behind in systems diagnostics compared to fields such
      as oncology. We define glaucomics as the integrated use of multi-omics and
      systems science approaches towards rational discovery, development, and tandem
      applications of diagnostics and therapeutics, for glaucoma specifically, and for
      personalized visual health, more broadly. We propose that glaucoma is one of the
      neglected lowest hanging fruits and actionable targets for omics and systems
      diagnostics in 21(st) century ophthalmology for the salient reasons we describe
      here. Additionally, we offer an analysis on two of the most pertinent neglected
      tropical diseases (NTDs), trachoma and river blindness, which continue to plague
      visual health in developing countries. We conclude with a call for research on
      omics applications in glaucoma and personalized visual health.

PMID- 24730383
TI  - Moderating Effects of Coping on Associations between Autonomic Arousal and
      Adolescent Internalizing and Externalizing Problems.
AB  - Few published studies have looked at the moderating role of coping styles on the
      association between stress reactivity and internalizing/externalizing problems
      despite theory suggesting that particular constellations of stress reactivity and
      coping may be uniquely problematic. The present study aimed to test the
      interactive effects of coping and psychophysiology on self- and parent-report
      broad-spectrum problems in a normative adolescent sample. Sixty-six late
      adolescents (ages 16-17; 60% female, 13% ethnic minority) completed
      questionnaires on coping, stressful life events, and behavioral/emotional
      problems, with parents also providing data on problems. In addition, skin
      conductance and heart rate data were obtained during a brief interview designed
      to elicit the feeling of reexperiencing a recent stressful experience. Path
      analytic results suggested evidence for several interaction effects between
      coping and skin conductance. Most commonly, the pattern of effects was consistent
      with a buffering effect for productive (or problem-focused) coping strategies
      against elevated internalizing and externalizing problems for individuals who
      demonstrated high physiological stress reactivity. Evidence for interaction
      effects related to respiratory sinus arrhythmia was less frequent and less
      consistent with a priori hypotheses. Although our cross-sectional results should
      be interpreted cautiously, the interactions reported here suggest that improving
      coping skills may be particularly beneficial for youth with high
      psychophysiological arousal. 

PMID- 24730381
TI  - Factors linking childhood experiences to adult romantic relationships among
      African Americans.
AB  - It is well known that a high-quality relationship with a romantic partner is
      related to a variety of positive outcomes associated with health and well-being.
      Establishing such relationships is an important developmental task for young
      adults, and past research indicates that there is a link between experiences in
      the family of origin and the success of later intimate relationships. It has been
      suggested that this association can be explained by the acquisition of social
      competencies (e.g., emotions, schemas, traits) that are acquired during childhood
      in the family of origin and, in turn, influence interaction with adult romantic
      partners. The current study builds on this foundation by identifying particular
      competencies expected to explain the association between childhood exposure to
      supportive and harsh parenting and later patterns of interaction with romantic
      partners. Specifically, we examine anger management, attachment style, hostile
      attribution bias, and self-control as potential mediators using prospective,
      longitudinal data from a sample of 345 African American young adults. Results
      from structural equation modeling indicate that each of the mediators in our
      study accounts for a significant portion of the effect of parenting on the
      quality of adult romantic relationships, although the constructs linking
      parenting to warm interactions with romantic partners are somewhat different from
      those that link parenting to hostile interactions with romantic partners. Even
      after accounting for the effect of the mediators, there is still a direct effect
      of parenting on both warm/loving and hostile/aggressive interactions with
      romantic partner. Implications for theory and practice are discussed.

PMID- 24730384
TI  - Intestinal wall thickness detected by multidetector spiral computed tomography
      enterography predicts the disease severity of Crohn's disease.
AB  - OBJECTIVE: Multidetector spiral computed tomography enterography (MSCTE) and
      ileocolonoscopy are used in evaluating inflammatory situation of Crohn's disease
      (CD) patients. The purpose of this study was to determine the disease severity of
      CD patients by combining the intestinal wall thickness by MSCTE with
      ileocolonoscopy. MATERIAL AND METHODS: This retrospective study included 50
      patients with terminal ileal CD. Diagnosis was confirmed based on clinical
      features, endoscopy, and pathology. Patients underwent both MSCTE and
      ileocolonoscopy. Ileal wall thickness was measured and the disease severity was
      evaluated by CD activity index (CDAI). Intestinal mucosal lesions were scored by
      the simple endoscopic score for CD (SES-CD). RESULTS: Of the 50 patients with
      active terminal ileal CD, the comparison of scores between SES-CD and CDAI showed
      significant association with Spearman's rank correlation coefficient (p < 0.01).
      There were statistically significant correlation between the wall thickness and
      the SES-CD (p < 0.0001) as well as CDAI (p < 0.001), respectively, but no
      significant correlation between the wall thickness and the C-reactive protein
      (CRP) was found (p = 0.43). Moreover, we found that the wall thickness was
      preferential to predict the disease severity in the terminal ileal CD.
      CONCLUSION: MSCTE, in combination with ileocolonoscopy, is reliable to identify
      disease severity in CD patients and provides more accurate information in the
      diagnosis and treatment.

PMID- 24730385
TI  - Effect of melamine-contaminated diet on tissue distribution of melamine and
      cyanuric acid, blood variables, and egg quality in laying hens.
AB  - 1. The aim of the study was to investigate the effect of melamine-contaminated
      feed (100 mg/kg) on the distribution of melamine and cyanuric acid in the tissues
      of laying hens. The effect of a 5-week melamine administration in feed on the egg
      quality and blood variables of layers was also investigated. 2. A total of twenty
      36-week-old ISA Brown layers were used in the experiment. The layers were equally
      divided into an experimental melamine group (n = 10) and a control group without
      melamine (n = 10). At the end of the experiment, samples of liver, kidney, breast
      and thigh muscles were collected from all hens and analysed for the presence of
      melamine and cyanuric acid by gas chromatography and tandem mass spectrometry. 3.
      Layers receiving the melamine-contaminated diet laid eggs with decreased eggshell
      strength. The decrease in shell strength was found in weeks 3 and 4 compared to
      the initial state (week 0) and week 1. 4. Hens receiving the melamine
      contaminated diet also exhibited a higher total red blood cell count and lower
      mean corpuscular haemoglobin compared to the control group. However, melamine at
      100 mg/kg feed had no effects on the blood variables of layers. 5. Melamine was
      detected in all analysed tissues of layers fed on the melamine-contaminated diet,
      with its mean concentrations decreasing in the following order: kidney (7.43
      mg/kg) > breast muscle (3.88 mg/kg) > liver (3.11 mg/kg) > thigh muscle (1.91
      mg/kg). The kidney and liver of layers fed on the melamine-contaminated diet also
      exhibited the presence of cyanuric acid. 6. On the basis of our results, it can
      be concluded that the biotransformation of melamine into cyanuric acid proceeded
      mainly in the liver, and cyanuric acid was eliminated in urine.

PMID- 24730388
TI  - How often and how consistently do symptoms directly precede criminal behavior
      among offenders with mental illness?
AB  - Although offenders with mental illness are overrepresented in the criminal
      justice system, psychiatric symptoms relate weakly to criminal behavior at the
      group level. In this study of 143 offenders with mental illness, we use data from
      intensive interviews and record reviews to examine how often and how consistently
      symptoms lead directly to criminal behavior. First, crimes rarely were directly
      motivated by symptoms, particularly when the definition of symptoms excluded
      externalizing features that are not unique to Axis I illness. Specifically, of
      the 429 crimes coded, 4% related directly to psychosis, 3% related directly to
      depression, and 10% related directly to bipolar disorder (including impulsivity).
      Second, within offenders, crimes varied in the degree to which they were directly
      motivated by symptoms. These findings suggest that programs will be most
      effective in reducing recidivism if they expand beyond psychiatric symptoms to
      address strong variable risk factors for crime like antisocial traits.

PMID- 24730389
TI  - Language style matching and police interrogation outcomes.
AB  - This research examined the coordination of interrogator and suspects' verbal
      behavior in interrogations. Sixty-four police interrogations were examined at the
      aggregate and utterance level using a measure of verbal mimicry known as Language
      Style Matching. Analyses revealed an interaction between confession and the
      direction of language matching. Interrogations containing a confession were
      characterized by higher rates of the suspect matching the interrogators' language
      style than interrogations without a confession. A sequence analysis of utterance
      level Language Style Matching revealed a divergence in the type of matching that
      occurred across outcome. There was a linear increase in interrogator-led matching
      for interrogations containing a confession and an increase in suspect-led
      matching for nonconfession interrogations. These findings suggest that police
      interrogations play out, in part, at the basic level of language coordination.

PMID- 24730386
TI  - Glucosamine-induced OGT activation mediates glucose production through cleaved
      Notch1 and FoxO1, which coordinately contributed to the regulation of maintenance
      of self-renewal in mouse embryonic stem cells.
AB  - We aimed to study the relationship between glucosamine and FoxO1/Notch in
      gluconeogenesis and maintenance of mouse embryonic stem cell (mESC) self-renewal.
      Glucosamine (GlcN) increased glucose production and gluconeogenic enzyme (G6Pase
      and PEPCK) expression. GlcN also increased the percentage of cells in S phase,
      number of cells, and the protein expression of cell cycle regulatory proteins
      that were blocked by 3-mercaptopicolinic acid (gluconeogenesis inhibitor) or
      glucose transporter (GLUT) 1 neutralizing antibody. GlcN increased the O-GlcNAc
      transferase (OGT)-dependent protein O-GlcNAc level. Moreover, inhibition of OGT
      (by ST045849) decreased glucose production. GlcN enhanced the expression of OGT
      dependent O-GlcNAcylated Notch1 and then increased the translocation of cleaved
      Notch1 to the nucleus. Moreover, GlcN stimulated the translocation of O
      GlcNAcylated FoxO1 to the nucleus. GlcN increased the binding between cleaved
      Notch1 and FoxO1 with CSL, a transcription factor, which was blocked by L-685,458
      (gamma-secretase inhibitor) or ST045849, respectively. Simultaneous blockage of
      cleaved Notch1 and FoxO1 also decreased the expression of G6Pase and PEPCK more
      significantly than that by inhibition of cleaved Notch1 alone or FoxO1 alone. In
      addition, GlcN maintained the undifferentiation status while depletion of Notch1
      and FoxO1 for 3 days decreased Oct4 and SSEA-1 expression and alkaline
      phosphatase activity or increased the mRNA expression of GATA4, Tbx5, Cdx2, and
      Fgf5. In conclusion, GlcN-induced OGT activation mediated glucose production
      through cleaved Notch1 and FoxO1, which contributed to the regulation of
      maintenance of self-renewal in mESCs. 

PMID- 24730390
TI  - Enhancement and electric charge-assisted tuning of nonlinear light generation in
      bipolar plasmonics.
AB  - We propose and experimentally demonstrate a new plasmonic nonlinear light
      generation (NLG) structure, termed plasmonic-enhanced, charge-assisted second
      harmonic generator (p-CASH), that not only achieves high second-harmonic
      generation (SHG) enhancement (76-fold), large SHG tunability by bias (8%/V), wide
      tuning range (280%), 7.8 * 10(-9) conversion efficiency, and high stability but
      also exhibits a SHG tuning, that is bipolar rather than unipolar, not due to the
      third-order nonlinear polarization term, hence fundamentally different from the
      classic electric field induced SHG-tuning (EFISH). We propose a new SHG tuning
      mechanism: the second-order nonlinear polarization term enhanced by plasmonic
      effects, changed by charge injection and negative oxygen vacancies movement, and
      is nearly 3 orders of magnitude larger than EFISH. p-CASH is a bipolar parallel
      plate capacitor with thin layers of plasmonic nanostructures, a TiOx
      (semiconductor and nonlinear) and a SiO2 (insulator) sandwiched between two
      electrodes. Fabrication of p-CASH used nanoimprint on 4" wafer and is scalable to
      wallpaper-sized areas. The new structure, new properties, and new understanding
      should open up various new designs and applications of NLG in various fields. 

PMID- 24730391
TI  - Copper-mediated oxidative transformation of N-allyl enamine carboxylates toward
      synthesis of azaheterocycles.
AB  - A method for synthesis of 3-azabicyclo[3.1.0]hex-2-enes has been developed by
      intramolecular cyclopropanation of readily available N-allyl enamine
      carboxylates. Two complementary reaction conditions, CuBr-mediated aerobic and
      CuBr2-catalyzed-PhIO2-mediated systems effectively induced stepwise
      cyclopropanation via carbocupration of alkenes. Oxidative cyclopropane ring
      opening of 5-substituted 3-azabicyclo[3.1.0]hex-2-enes was also developed for
      synthesis of highly substituted pyridines. In addition, diastereoselective
      reduction of 3-azabicyclo[3.1.0]hex-2-enes to 3-azabicyclo[3.1.0]hexanes was
      achieved using NaBH3CN in the presence of acetic acid. 

PMID- 24730392
TI  - One-step dip coating of zwitterionic sulfobetaine polymers on hydrophobic and
      hydrophilic surfaces.
AB  - Zwitterionic sulfobetaine polymers with a catechol chain end (DOPA-PSB) were
      applied to a variety of hydrophobic polymer sheets and fibers. In addition, a
      silica surface was tested as a representative hydrophilic substrate. The polymer
      coated surfaces showed significantly lower fouling levels than uncoated controls.
      Because of the anti-polyelectrolyte nature of sulfobetaine zwitterionic polymers,
      the effect of salt concentration on the coating solutions and the quality of the
      polymer coating against fouling are studied. The coating method involves only
      water-based solutions, which is compatible with most surfaces and is
      environmentally friendly. To demonstrate the versatility of the reported method,
      we evaluated the fouling levels of the polymer coating on commonly used polymeric
      surfaces such as polypropylene (PP), polydimethylsiloxane (PDMS), polystyrene
      (PS), nylon, polyvinyl chloride (PVC), and poly(methyl methacrylate) (PMMA). 

PMID- 24730393
TI  - Antidepressant-like behavioral, anatomical, and biochemical effects of petroleum
      ether extract from maca (Lepidium meyenii) in mice exposed to chronic
      unpredictable mild stress.
AB  - Maca has been consumed as a medical food in Peru for thousands of years, and
      exerts anxiolytic and antidepressant effects. Our present study aimed to evaluate
      the behavior and anatomical and biochemical effects of petroleum ether extract
      from maca (ME) in the chronic unpredictable mild stress (CUMS) model of
      depression in mice. Three different doses of maca extract (125, 250, and 500
      mg/kg) were orally administrated in the six-week CUMS procedure. Fluoxetine (10
      mg/kg) was used as a positive control drug. Maca extract (250 and 500 mg/kg)
      significantly decreased the duration of immobility time in the tail suspension
      test. After treatment with maca extract (250 and 500 mg/kg), the granule cell
      layer in the dentate gyrus appeared thicker. Maca extract (250 and 500 mg/kg)
      also induced a significant reduction in corticosterone levels in mouse serum. In
      mouse brain tissue, after six weeks of treatment, noradrenaline and dopamine
      levels were increased by maca extract, and the activity of reactive oxygen
      species was significantly inhibited. Serotonin levels were not significantly
      altered. These results demonstrated that maca extract (250 and 500 mg/kg) showed
      antidepressant-like effects and was related to the activation of both
      noradrenergic and dopaminergic systems, as well as attenuation of oxidative
      stress in mouse brain.

PMID- 24730394
TI  - Mortality in inflammatory bowel disease patients under 65 years of age.
AB  - OBJECTIVE: To assess mortality in inflammatory bowel disease (IBD) patients under
      65 years of age and to identify the factors related to death in this age group.
      METHODS. We studied 2570 IBD patients who were diagnosed as having disease before
      65 years of age and attended a single tertiary referral center area between 1983
      and 2012. Follow-up was censored at 65 years. The causes of death were determined
      from death certificates obtained from the Irish registry office of births,
      marriages and deaths. Observed all-cause survival was compared with expected
      survival of persons of the same age and sex in the general population. Expected
      survival was obtained from national life tables produced by the central
      statistics office. Survival estimates were calculated for disease type, disease
      site, gender, the presence of primary sclerosing cholangitis (PSC),
      immunomodulator use, biologic therapy use, presence of fistulating disease and
      prior surgery. RESULTS: Fifty-two deaths were reported in the population younger
      than 65 years, of which 41 were IBD related. We found little difference in
      survival in the first 25 years of follow-up, but relative survival decreased in
      both the Crohn's disease (CD) and ulcerative colitis (UC) cohort thereafter, so
      that 30-year mortality was excessive in both groups. An adjusted multivariate
      regression analysis of patients with CD identified PSC as the only predictor of
      premature mortality (p = 0.003). PSC was also identified as the only independent
      predictor of mortality in UC patients (p = 0.03). CONCLUSIONS: The presence of
      PSC poses the greatest risk for mortality in both UC and CD.

PMID- 24730395
TI  - Low and moderate doses of ionizing radiation up to 2 Gy modulate transmigration
      and chemotaxis of activated macrophages, provoke an anti-inflammatory cytokine
      milieu, but do not impact upon viability and phagocytic function.
AB  - Benign painful and inflammatory diseases have been treated for decades with
      low/moderate doses of ionizing radiation (LD-X-irradiation). Tissue macrophages
      regulate initiation and resolution of inflammation by the secretion of cytokines
      and by acting as professional phagocytes. Having these pivotal functions, we were
      interested in how activated macrophages are modulated by LD-X-irradiation, also
      with regard to radiation protection issues and carcinogenesis. We set up an ex
      vivo model in which lipopolysaccharide pre-activated peritoneal macrophages
      (pMPhi) of radiosensitive BALB/c mice, mimicking activated macrophages under
      inflammatory conditions, were exposed to X-irradiation from 0.01 Gy up to 2 Gy.
      Afterwards, the viability of the pMPhi, their transmigration and chemotaxis, the
      phagocytic behaviour, the secretion of inflammatory cytokines and underlying
      signalling pathways were determined. Exposure of pMPhi up to a single dose of 2
      Gy did not influence their viability and phagocytic function, an important fact
      regarding radiation protection. However, significantly reduced migration, but
      increased chemotaxis of pMPhi after exposure to 0.1 or 0.5 Gy, was detected. Both
      might relate to the resolution of inflammation. Cytokine analyses revealed that,
      in particular, the moderate dose of 0.5 Gy applied in low-dose radiotherapy for
      inflammatory diseases results in an anti-inflammatory cytokine microenvironment
      of pMPhi, as the secretion of the proinflammatory cytokine interleukin (IL)-1beta
      was reduced and that of the anti-inflammatory cytokine transforming growth factor
      (TGF)-beta increased. Further, the reduced secretion of IL-1beta correlated with
      reduced nuclear translocation of nuclear factor (NF)-kappaB p65, starting at
      exposure of pMPhi to 0.5 Gy of X-irradiation. We conclude that inflammation is
      modulated by LD-X-irradiation via changing the inflammatory phenotype of
      macrophages. 

PMID- 24730396
TI  - Ruthenium-catalyzed synthesis of isoquinolones with 8-aminoquinoline as a
      bidentate directing group in C-H functionalization.
AB  - Ruthenium-catalyzed oxidative annulation of N-quinolin-8-yl-benzamides with
      alkynes in open air has been achieved using 8-aminoquinolinyl moiety as a
      bidentate directing group in the presence of Cu(OAc)2.H2O as an oxidant. This
      reaction offers a broad substrate scope, and both symmetrical and unsymmetrical
      alkynes can be applied. High regioselectivity was achieved in the case of
      unsymmetrical (aryl)alkynes. Reaction with heteroaryl amides was also successful
      in this catalytic process. A ruthenium-N-quinolin-8-yl-benzamide complex was
      isolated in the absence of alkyne; in the absence of both N-quinolin-8-yl
      benzamide and alkyne, in contrast to literature, only the monoacetate complex
      RuCl(OAc)(p-cymene), but not the bis-acetate complex Ru(OAc)2(p-cymene), was
      isolated. These data suggest that this reaction may proceed via N,N-bidentate
      chelate complex. Key products were characterized by X-ray crystallography. 

PMID- 24730397
TI  - No benefit to prehospital initiation of therapeutic hypothermia in out-of
      hospital cardiac arrest: a systematic review and meta-analysis.
AB  - OBJECTIVES: The aim of this review was to define the effect of prehospital
      therapeutic hypothermia (TH) on survival and neurologic recovery in patients who
      have suffered out-of-hospital cardiac arrest (OHCA). METHODS: Included in this
      review are randomized trials assessing the effect of prehospital TH in adult
      patients suffering nontraumatic OHCA. Trials assessing the effect of in-hospital
      TH were excluded. Only studies with a low risk of bias were eligible for meta
      analysis. A medical librarian searched PubMed, Ovid, EMBASE, Ovid Global Health,
      the Cochrane Library, Guidelines.gov, EM Association Websites, CenterWatch, IFPMA
      Clinical Trial Results Portal, CINAHL, ProQuest, and the Emergency Medical
      Abstracts Database without language restrictions. Clinicaltrials.gov was searched
      for unpublished studies. Bibliographies were hand searched and experts in the
      field were queried about other published or unpublished trials. Using
      standardized forms, two authors independently extracted data from all included
      trials. Results from high-quality trials were pooled using a random-effects
      model. Two authors, using the Cochrane risk of bias tool, assessed risk of bias
      independently. RESULTS: Of 740 citations, six trials met inclusion criteria. Four
      trials were at a low risk of bias and were included in the meta-analysis (N=715
      patients). Pooled analysis of these trials revealed no difference in overall
      survival (relative risk [RR]=0.98, 95% CI=0.79 to 1.21) or good neurologic
      outcome (RR=0.96, 95% CI=0.76 to 1.22) between patients randomized to prehospital
      TH versus standard therapy. Heterogeneity was low for both survival and
      neurologic outcome (I2=0). CONCLUSIONS: Randomized trial data demonstrate no
      important patient benefit from prehospital initiation of TH. Pending the results
      of ongoing larger trials, resources dedicated to this intervention may be better
      spent elsewhere.

PMID- 24730398
TI  - Recurrent and high-frequency use of the emergency department by pediatric
      patients.
AB  - OBJECTIVES: The authors sought to describe the epidemiology of and risk factors
      for recurrent and high-frequency use of the emergency department (ED) by
      children. METHODS: This was a retrospective cohort study using a database of
      children aged 0 to 17 years, inclusive, presenting to 22 EDs of the Pediatric
      Emergency Care Applied Research Network (PECARN) during 2007, with 12-month
      follow-up after each index visit. ED diagnoses for each visit were categorized as
      trauma, acute medical, or chronic medical conditions. Recurrent visits were
      defined as any repeat visit; high-frequency use was defined as four or more
      recurrent visits. Generalized estimating equations (GEEs) were used to measure
      the strength of associations between patient and visit characteristics and
      recurrent ED use. RESULTS: A total of 695,188 unique children had at least one ED
      visit each in 2007, with 455,588 recurrent ED visits in the 12 months following
      the index visits. Sixty-four percent of patients had no recurrent visits, 20% had
      one, 8% had two, 4% had three, and 4% had four or more recurrent visits. Acute
      medical diagnoses accounted for most visits regardless of the number of recurrent
      visits. As the number of recurrent visits per patient rose, chronic diseases were
      increasingly represented, with asthma being the most common ED diagnosis. Trauma
      related diagnoses were more common among patients without recurrent visits than
      among those with high-frequency recurrent visits (28% vs. 9%; p<0.001). High
      frequency recurrent visits were more often within the highest severity score
      classifications. In multivariable analysis, recurrent visits were associated with
      younger age, black or Hispanic race or ethnicity, and public health insurance.
      CONCLUSIONS: Risk factors for recurrent ED use by children include age, race and
      ethnicity, and insurance status. Although asthma plays an important role in
      recurrent ED use, acute illnesses account for the majority of recurrent ED
      visits.

PMID- 24730399
TI  - Topical tetracaine used for 24 hours is safe and rated highly effective by
      patients for the treatment of pain caused by corneal abrasions: a double-blind,
      randomized clinical trial.
AB  - OBJECTIVES: The objective of this study was to test the hypothesis that topical
      tetracaine would be safe to use for 24 hours and would not affect corneal
      healing, that patients would experience more pain relief, and that patients would
      perceive tetracaine to be more effective than saline eye drops for the treatment
      of pain caused by corneal abrasions. METHODS: The study was a 12-month,
      prospective, double-blind, randomized trial of tetracaine versus saline set in
      the emergency department (ED) of a regional tertiary care teaching hospital. A
      total of 116 patients presenting with uncomplicated corneal abrasions were
      included in this study. The intervention was either undiluted, preservative-free,
      topical tetracaine hydrochloride 1% or saline, applied up to every 30 minutes
      while awake for 24 hours. Main safety outcome measures were repeat ED
      examinations at 48 hours with fluorescein staining and slit-lamp examination, 1
      week and 1-month telephone interviews with additional examinations as needed, and
      monitoring of charts for complications. Secondary outcome measures were 100-mm
      visual analogue scale (VAS) pain scores recorded every 2 hours while awake for 48
      hours and patient-perceived overall effectiveness using a numeric rating scale
      (NRS) of 0 to 10 obtained during telephone interviews. RESULTS: At least one
      follow-up encounter was completed on each of the 116 patients. No complications
      specifically attributed to topical anesthetic use occurred in the 59 patients in
      the tetracaine group, and the binomial probability confidence interval (CI) of
      this occurring is 0 to 6.1. There was no significant difference in corneal
      healing as measured by the percentage of patients with persistent fluorescein
      uptake at 48 hours between the two groups (23.9% vs. 21.3%, difference=2.6%, 95%
      CI=-14% to 20%, p=0.761) or persistent symptoms at 48 hours (21.7% vs. 21.3%,
      difference=0.4%, 95% CI=-16% to 17%, p=0.957). There was no clinical difference
      in VAS pain scores between the groups. Patients in the tetracaine group rated the
      study drugs' overall effectiveness significantly higher on the NRS (7.7 vs. 3.9)
      compared to patients in the saline group (difference=3.9, 95% CI=2.4 to 5.3,
      p<0.0005). CONCLUSIONS: Topical tetracaine used for 24 hours is safe, and while
      there was no significant difference in patient VAS pain ratings over time,
      patient surveys on overall effectiveness showed that patients perceived
      tetracaine to be significantly more effective than saline.

PMID- 24730400
TI  - Role of autophagy and apoptosis in wound tissue of deep second-degree burn in
      rats.
AB  - OBJECTIVES: The pathogenesis of burn wound progression is poorly understood.
      Contributing factors include continuous loss of blood perfusion, excessive
      inflammation, and elevated apoptosis levels in wound tissue. Macroautophagy (here
      referred to simply as "autophagy") is associated with many chronic diseases. The
      authors hypothesized that autophagy is involved in burn wound progression in a
      rat model of deep second-degree burn. METHODS: Deep second-degree burns were
      modeled using a brass rod heated to 100 degrees C applied for 6 seconds to the
      back skin of Wistar rats. Full-thickness biopsies were obtained from burned and
      nonburned controls at several times postburn. Western blotting and
      immunohistochemical (IHC) staining determined expression of the autophagy markers
      Light Chain 3 (LC3) and beclin-1. Apoptosis was determined by terminal
      deoxynucleoitidyl transferase mediated nick end labeling (TUNEL) assay and laser
      Doppler flowmetry (LDF)-measured tissue perfusion. Myeloperoxidase (MPO) activity
      assay measured inflammation. Hematoxylin and eosin (H&E) and Masson's trichrome
      staining-determined pathology and wound depth. RESULTS: The LC3 and beclin-1
      protein level in burn wounds decreased to one-fourth of normal levels (p<0.01)
      over 24 hours and then began to increase but still did not reach their normal
      level. TUNEL-positive cells in burn wounds were 3.7-fold (p<0.01) elevated over
      48 hours and then decreased slightly, yet still remained higher than in normal
      skin. The burn wound progressed in depth over 72 hours. In addition, significant
      decrease in LDF values and upregulation of MPO activity were observed. Enhanced
      LC3-positive cells were observed in the deep dermal layer of burn wounds as shown
      by IHC staining. CONCLUSIONS: A reduction in autophagy and blood flow and an
      increase in apoptosis and inflammation were observed in burn wounds early during
      the course of burn injury progression. This suggests that autophagy, complemented
      by apoptosis, play important roles in burn progression. Enhanced autophagy in the
      deep dermis may be a prosurvival mechanism against ischemia and inflammation
      after burn injury.

PMID- 24730401
TI  - Effects of potassium/lidocaine-induced cardiac standstill during cardiopulmonary
      resuscitation in a pig model of prolonged ventricular fibrillation.
AB  - OBJECTIVES: Several studies in patients who underwent open heart surgery found
      that myocardial ischemic damage was reduced by potassium cardioplegia combined
      with lidocaine infusion. The authors evaluated the effects of potassium/lidocaine
      induced cardiac standstill during conventional cardiopulmonary resuscitation
      (CPR) on myocardial injury and left ventricular dysfunction after resuscitation
      from prolonged ventricular fibrillation (VF) cardiac arrest in a pig model.
      METHODS: Ventricular fibrillation was induced in 16 pigs, and circulatory arrest
      was maintained for 14 minutes. Animals were then resuscitated by standard CPR.
      Animals were randomized at the start of CPR to receive 20 mL of saline (control
      group) or 0.9 mEq/kg potassium chloride and 1.2 mg/kg lidocaine diluted to 20 mL
      (K-lido group). RESULTS: Seven animals in each group achieved return of
      spontaneous circulation (ROSC; p=1.000). Four of the K-lido group animals (50%)
      achieved ROSC without countershock. Resuscitated animals in the K-lido group
      required fewer countershocks (p=0.004), smaller doses of epinephrine (p=0.009),
      and shorter durations of CPR (p=0.004) than did the control group. The
      uncorrected troponin-I at 4 hours after ROSC was lower in the K-lido group
      compared with the control group (2.82 ng/mL, 95% confidence interval [CI]=1.07 to
      3.38 ng/mL vs. 6.55 ng/mL, 95% CI=4.84 to 13.30 ng/mL; p=0.025), although the
      difference was not significant after Bonferroni correction. The magnitude of
      reduction in left ventricular ejection fraction (LVEF) between baseline and 1
      hour after ROSC was significantly lower in the K-lido group (26.5%, SD+/-6.1% vs.
      39.1%, SD+/-6.8%; p=0.004). CONCLUSIONS: In a pig model of untreated VF cardiac
      arrest for 14 minutes, resuscitation with potassium/lidocaine-induced cardiac
      standstill during conventional CPR tended to reduce myocardial injury and
      decreased the severity of postresuscitation myocardial dysfunction significantly.

PMID- 24730402
TI  - The association between pretest probability of coronary artery disease and stress
      test utilization and outcomes in a chest pain observation unit.
AB  - OBJECTIVES: Cardiology consensus guidelines recommend use of the Diamond and
      Forrester (D&F) score to augment the decision to pursue stress testing. However,
      recent work has reported no association between pretest probability of coronary
      artery disease (CAD) as measured by D&F and physician discretion in stress test
      utilization for inpatients. The author hypothesized that D&F pretest probability
      would predict the likelihood of acute coronary syndrome (ACS) and a positive
      stress test and that there would be limited yield to diagnostic testing of
      patients categorized as low pretest probability by D&F score who are admitted to
      a chest pain observation unit (CPU). METHODS: This was a prospective
      observational cohort study of consecutively admitted CPU patients in a large
      volume academic urban emergency department (ED). Cardiologists rounded on all
      patients and stress test utilization was driven by their recommendations.
      Inclusion criteria were as follows: age>18 years, American Heart Association
      (AHA) low/intermediate risk, nondynamic electrocardiograms (ECGs), and normal
      initial troponin I. Exclusion criteria were as follows: age older than 75 years
      with a history of CAD. A D&F score for likelihood of CAD was calculated on each
      patient independent of patient care. Based on the D&F score, patients were
      assigned a priori to low-, intermediate-, and high-risk groups (<10, 10 to 90,
      and >90%, respectively). ACS was defined by ischemia on stress test, coronary
      artery occlusion of >=70% in at least one vessel, or elevations in troponin I
      consistent with consensus guidelines. A true-positive stress test was defined by
      evidence of reversible ischemia and subsequent angiographic evidence of critical
      stenosis or a discharge diagnosis of ACS. An estimated 3,500 patients would be
      necessary to have 1% precision around a potential 0.3% event rate in low-pretest
      probability patients. Categorical comparisons were made using Pearson chi-square
      testing. RESULTS: A total of 3,552 patients with index visits were enrolled over
      a 29-month period. The mean (+/-standard deviation [SD]) age was 51.3 (+/-9.3)
      years. Forty-nine percent of patients received stress testing. Pretest
      probability based on D&F score was associated with stress test utilization
      (p<0.01), risk of ACS (p<0.01), and true-positive stress tests (p=0.03). No
      patients with low pretest probability were subsequently diagnosed with ACS (95%
      CI=0 to 0.66%) or had a true-positive stress test (95% CI=0 to 1.6%).
      CONCLUSIONS: Physician discretionary decision-making regarding stress test use is
      associated with pretest probability of CAD. However, based on the D&F score, low
      pretest-probability patients who meet CPU admission criteria are very unlikely to
      have a true-positive stress test or eventually receive a diagnosis of ACS, such
      that observation and stress test utilization may be obviated.

PMID- 24730403
TI  - Comparison of the reusable standard GlideScope(r) video laryngoscope and the
      disposable cobalt GlideScope(r) video laryngoscope for tracheal intubation in an
      academic emergency department: a retrospective review.
AB  - OBJECTIVES: The objective was to compare the first-pass success and clinical
      performance characteristics of the reusable standard GlideScope(r) video
      laryngoscope (sGVL) and the disposable Cobalt GlideScope(r) video laryngoscope
      (cGVL). METHODS: This was a retrospective analysis of prospectively collected
      data recorded into a continuous quality improvement database at an urban academic
      emergency department (ED). The intent of the database is to evaluate operator
      performance and to track practice patterns used for intubation in the ED. Between
      July 1, 2007, and June 30, 2013, operators recorded all consecutive intubations
      performed in the ED. The database included patient demographics and detailed
      information about each intubation, such as device(s) used, reason for device
      selection, method of intubation, difficult airway characteristics, number of
      intubation attempts, and outcome of each attempt. The operator also evaluated the
      presence of lens fogging and extent of lens contamination. The primary outcome
      measure was first-pass success. Secondary outcome measures were ultimate success,
      Cormack-Lehane (CL) view of the airway, presence of lens fogging, and extent of
      lens contamination. Only adult patients age 18 years or older intubated with the
      sGVL or cGVL using a stylet, and who had data forms completed at the time of
      intubation, were included in this study. RESULTS: A total of 583 intubations were
      included in the study, 504 with the sGVL and 79 with cGVL. First pass success was
      achieved in 81.0% (95% confidence interval [CI]=77.3% to 84.3%) of patients in
      the sGVL group and in 58.2% (95% CI=46.6% to 69.2%) of patients in the cGVL
      group. In a multivariate logistic regression analysis, the sGVL was associated
      with a higher first pass success than the cGVL (odds ratio [OR]=3.3, 95% CI=1.9
      to 5.8). The ultimate success of the sGVL was 92.1% (95% CI=89.4% to 94.3%) and
      the cGVL was 72.2% (95% CI=60.9% to 81.7%). A CL grade I or II view was obtained
      in 93.2% (95% CI=90.7% to 95.3%) in the sGVL group and 86.1% (95% CI=76.5% to
      92.8%) in the cGVL group. Lens fogging occurred in 33.3% (95% CI=29.2% to 37.6%)
      of the cases in the sGVL group and 59.5% (95% CI=47.9% to 70.4%) of the cases in
      the cGVL group. Significant lens contamination occurred in 5.0% (95% CI=3.2% to
      7.2%) of the sGVL group and 21.5% (95% CI=13.1% to 32.2%) of the cGVL group.
      CONCLUSIONS: In this observational study, the sGVL had higher first pass and
      overall success than the disposable cGVL. The cGVL had significantly higher
      incidence of lens fogging and contamination, which may partially account for its
      lower success. A prospective randomized trial is needed to confirm these
      findings.

PMID- 24730404
TI  - Use of ultrasound guidance for central venous catheter placement: survey from the
      American Board of Emergency Medicine Longitudinal Study of Emergency Physicians.
AB  - OBJECTIVES: The objective was to survey practicing emergency physicians (EPs)
      across the United States regarding the frequency of using ultrasound (US)
      guidance in central venous catheter (CVC) placement and, secondarily, to
      determine factors associated with the use or barriers to the use of US guidance.
      METHODS: This was a cross-sectional survey mailed to presumed practicing EPs as
      part of the American Board of Emergency Medicine (ABEM)'s longitudinal study of
      EPs. The selection process used stratified, random sampling of cohorts thought to
      represent four different stages within the development of the specialty of
      emergency medicine (EM). Multivariable logistic regression was used to identify
      independent factors associated with both high comfort using US guidance and high
      percentage usage of US guidance. RESULTS: The survey was mailed to 1,165
      subjects, and the response rate was 79%. The median number of years of practice
      was 20 (interquartile range [IQR]=7 to 28 years). As their primary practice
      setting, 64% work in private or community hospitals, 60% received training in US
      guided vascular access, and 44% never use US guidance in placing CVCs. Barriers
      differed in those who never use US and those who sometimes or always used US
      guidance. In those who never use US, top barriers were insufficient training
      (67%) and lack of equipment (25%). In those who use US, top barriers were the
      perceptions that US was too time-consuming (27%) and that the preferred site was
      not amenable to US (24%). Independent factors associated with high comfort and
      high-percentage use of US guidance were training in US-guided vascular access
      (adjusted odds ratio=5.1 [high comfort]; 95% confidence interval [CI]=2.6 to
      10.1; adjusted odds ratio 11.1=(high percentage); 95% CI=5.0 to 24.8) and being a
      recent residency graduate. CONCLUSIONS: Among EPs, the translation of evidence to
      clinical practice regarding the benefits of US guidance for CVC placement is poor
      and still faces many barriers. Training and education are potentially the best
      ways to overcome such barriers.

PMID- 24730405
TI  - Geriatric syndromes predict postdischarge outcomes among older emergency
      department patients: findings from the interRAI Multinational Emergency
      Department Study.
AB  - OBJECTIVES: Identifying older emergency department (ED) patients with clinical
      features associated with adverse postdischarge outcomes may lead to improved
      clinical reasoning and better targeting for preventative interventions. Previous
      studies have used single-country samples to identify limited sets of determinants
      for a limited number of proxy outcomes. The objective of this study was to
      identify and compare geriatric syndromes that influence the probability of
      postdischarge outcomes among older ED patients from a multinational context.
      METHODS: A multinational prospective cohort study of ED patients aged 75 years or
      older was conducted. A total of 13 ED sites from Australia, Belgium, Canada,
      Germany, Iceland, India, and Sweden participated. Patients who were expected to
      die within 24 hours or did not speak the native language were excluded. Of the
      2,475 patients approached for inclusion, 2,282 (92.2%) were enrolled. Patients
      were assessed at ED admission with the interRAI ED Contact Assessment, a
      geriatric ED assessment. Outcomes were examined for patients admitted to a
      hospital ward (62.9%, n=1,436) or discharged to a community setting (34.0%,
      n=775) after an ED visit. Overall, 3% of patients were lost to follow-up.
      Hospital length of stay (LOS) and discharge to higher level of care was recorded
      for patients admitted to a hospital ward. Any ED or hospital use within 28 days
      of discharge was recorded for patients discharged to a community setting.
      Unadjusted and adjusted odds ratios (ORs) were used to describe determinants
      using standard and multilevel logistic regression. RESULTS: A multi-country model
      including living alone (OR=1.78, p<=0.01), informal caregiver distress (OR=1.69,
      p=0.02), deficits in ambulation (OR=1.94, p<=0.01), poor self-report (OR = 1.84,
      p<=0.01), and traumatic injury (OR=2.18, p<=0.01) best described older patients
      at risk of longer hospital lengths of stay. A model including recent ED visits
      (OR=2.10, p<=0.01), baseline functional impairment (OR=1.68, p<=0.01), and
      anhedonia (OR=1.73, p<=0.01) best described older patients at risk of proximate
      repeat hospital use. A sufficiently accurate and generalizable model to describe
      the risk of discharge to higher levels of care among admitted patients was not
      achieved. CONCLUSIONS: Despite markedly different health care systems, the
      probability of long hospital lengths of stay and repeat hospital use among older
      ED patients is detectable at the multinational level with moderate accuracy. This
      study demonstrates the potential utility of incorporating common geriatric
      clinical features in routine clinical examination and disposition planning for
      older patients in EDs.

PMID- 24730406
TI  - The effect of an emergency department dedicated midtrack area on patient flow.
AB  - BACKGROUND: Emergency department (ED) crowding negatively affects quality of care
      and disproportionately affects medium-acuity (Emergency Severity Index [ESI]
      level 3) patients. The effect of a dedicated area in the ED focused on these
      patients has not been well studied. OBJECTIVES: The objective was to find out the
      operational effect of a midtrack area dedicated to the evaluation and safe
      disposition of uncomplicated medium-acuity (ESI 3) patients. METHODS: This was a
      24-month pre-/postintervention study to evaluate the effect of implementation of
      a dedicated midtrack area at an urban tertiary academic adult ED. The midtrack
      had three examination rooms and three hallway stretchers for ongoing treatment
      staffed by an attending physician and two registered nurses (RNs). Besides the
      two additional RNs representing a 3.4% increase in total daily nursing hours, the
      intervention required no additional ED resources. The midtrack area was open from
      1 p.m. to 9 p.m. on weekdays, corresponding to peak ED arrival rates. All
      patients presenting during weekdays were included, excluding patients triaged
      directly to the trauma bay or psychiatric unit or who expired in the ED. The main
      outcomes were left without being seen (LWBS) rates and ED length of stay (LOS),
      adjusting for patient volume, daily total patient hours (a proxy for ED
      crowding), and acuity. RESULTS: A total of 91,903 patients were included for
      analysis during the study period including 261 pre- and 256 postintervention
      days. Comparing the pre- and postintervention periods, mean ED daily visits (173
      vs. 182) and mean total daily patient hours (889 vs. 942) were all significantly
      higher in the postintervention period (p<0.0001). There was no significant change
      in percentage of patients with high triage acuity levels. Despite this increase
      in volume and crowding, the unadjusted and adjusted LWBS rates decreased from
      6.85% to 4.46% (p<0.0001) and from 7.33% to 3.97% (p<0.0001), respectively. The
      mean LOS for medium-acuity patients also decreased by 39.2 minutes (p<0.0001).
      For high-acuity patients, there was no significant change in the mean time to
      room (14.69 minutes vs. 15.21 minutes, p=0.07); however, their mean LOS increased
      by 24 minutes (331 minutes vs. 355 minutes, p<0.0001). CONCLUSIONS:
      Implementation of a midtrack area dedicated to caring for uncomplicated medium
      acuity (ESI 3) patients was associated with a decrease in overall ED LWBS rates
      and ED LOS for medium-acuity patients.

PMID- 24730408
TI  - Injury-related visits and comorbid conditions among homeless persons presenting
      to emergency departments.
AB  - OBJECTIVES: The authors examined the clinical characteristics of homeless
      patients presenting to emergency departments (EDs) in the United States, with a
      focus on unintentional and intentional injury events and related comorbid
      conditions. METHODS: The study included a nationally representative sample of
      patients presenting to EDs with data obtained from the 2007 through 2010 National
      Hospital Ambulatory Medical Care Survey (NHAMCS). Descriptive and analytical
      epidemiologic analyses were employed to examine injuries among homeless patients.
      RESULTS: Homeless persons made 603,000 visits annually to EDs, 55% of which were
      for injuries, with the majority related to unintentional (52%) and self-inflicted
      (23%) injuries. Multivariate logistic regression analyses revealed that homeless
      patients had a higher odds of presenting with injuries related to unintentional
      (odds ratio [OR]=1.4. 95% confidence interval [CI]=1.1 to 1.9), self-inflicted
      (OR=6.0, 95% CI=3.7 to 9.5), and assault (OR=3.0, 95% CI=1.5 to 5.9) injuries.
      CONCLUSIONS: A better understanding of the injuries affecting homeless
      populations may provide medical and public health professionals insight into more
      effective ways to intervene and limit further morbidity and mortality related to
      specific injury outcomes.

PMID- 24730407
TI  - Occult pneumothoraces in children with blunt torso trauma.
AB  - OBJECTIVES: Plain chest x-ray (CXR) is often the initial screening test to
      identify pneumothoraces in trauma patients. Computed tomography (CT) scans can
      identify pneumothoraces not seen on CXR ("occult pneumothoraces"), but the
      clinical importance of these radiographically occult pneumothoraces in children
      is not well understood. The objectives of this study were to determine the
      proportion of occult pneumothoraces in injured children and the rate of treatment
      with tube thoracostomy among these children. METHODS: This was a planned substudy
      from a large prospective multicenter observational cohort study of children
      younger than 18 years old evaluated in emergency departments (EDs) in the
      Pediatric Emergency Care Applied Research Network (PECARN) for blunt torso trauma
      from May 2007 to January 2010. Children with CXRs as part of their trauma
      evaluations were included for analysis. The faculty radiologist interpretations
      of the CXRs and any subsequent imaging studies, including CT scans, were reviewed
      for the absence or presence of pneumothoraces. An "occult pneumothorax" was
      defined as a pneumothorax that was not identified on CXR, but was subsequently
      demonstrated on cervical, chest, or abdominal CT scan. Rates of pneumothoraces
      and placement of tube thoracostomies and rate differences with 95% confidence
      intervals (CIs) were calculated. RESULTS: Of 12,044 enrolled in the parent study,
      8,020 (67%) children (median age=11.3 years, interquartile range [IQR]=5.3 to
      15.2 years) underwent CXRs in the ED, and these children make up the study
      population. Among these children, 4,276 had abdominal CT scans performed within
      24 hours. A total of 372 of 8,020 children (4.6%; 95% CI=4.2% to 5.1%) had
      pneumothoraces identified by CXR and/or CT. The CXRs visualized pneumothoraces in
      148 patients (1.8%; 95% CI=1.6% to 2.2%), including one false-positive
      pneumothorax, which was identified on CXR, but was not demonstrated on CT. Occult
      pneumothoraces were present in 224 of 372 (60.2%; 95% CI=55.0% to 65.2%) children
      with pneumothoraces. Tube thoracostomies were performed in 85 of 148 (57.4%; 95%
      CI=49.0% to 65.5%) children with pneumothoraces on CXR and in 35 of 224 (15.6%;
      95% CI=11.1% to 21.1%) children with occult pneumothoraces (rate difference=
      41.8%; 95% CI=-50.8 to -32.3%). CONCLUSIONS: In pediatric patients with blunt
      torso trauma, pneumothoraces are uncommon, and most are not identified on the ED
      CXR. Nearly half of pneumothoraces, and most occult pneumothoraces, are managed
      without tube thoracostomy. Observation, including in children requiring
      endotracheal intubation, should be strongly considered during the initial
      management of children with occult pneumothoraces.

PMID- 24730409
TI  - The core content of clinical ultrasonography fellowship training.
AB  - The purpose of developing a core content for subspecialty training in clinical
      ultrasonography (US) is to standardize the education and qualifications required
      to provide oversight of US training, clinical use, and administration to improve
      patient care. This core content would be mastered by a fellow as a separate and
      unique postgraduate training, beyond that obtained during an emergency medicine
      (EM) residency or during medical school. The core content defines the training
      parameters, resources, and knowledge of clinical US necessary to direct clinical
      US divisions within medical specialties. Additionally, it is intended to inform
      fellowship directors and candidates for certification of the full range of
      content that might appear in future examinations. This article describes the
      development of the core content and presents the core content in its entirety. 

PMID- 24730410
TI  - The timing of therapeutic hypothermia initiation.

PMID- 24730411
TI  - Recurrent ED visits by children: where do we go from here?

PMID- 24730412
TI  - Dogma challenged: tetracaine for corneal abrasions?

PMID- 24730416
TI  - A novel prognostic model for patients with sarcomatoid renal cell carcinoma.
AB  - OBJECTIVE: To demonstrate sarcomatoid differentiation is an independent
      prognostic feature for patients with grade 4 renal cell carcinoma (RCC) with or
      without distant metastases. To identify independent predictors of survival,
      evaluate the correlation between the amount of sarcomatoid differentiation and
      cancer-specific survival (CSS), and to design a multivariate prognostic model for
      patients with sarcomatoid RCC. PATIENTS AND METHODS: We used the Mayo Clinic
      Nephrectomy Registry to identify 204 post-nephrectomy patients with sarcomatoid
      variant RCC, as well as 207 patients with unilateral grade 4 RCC without
      sarcomatoid features for comparison. All slides were reviewed by one pathologist.
      CSS was estimated using the Kaplan-Meier method. The associations of clinical and
      pathological features with death from RCC were evaluated using Cox proportional
      hazards regression models. RESULTS: For all patients with grade 4 RCC, the
      presence of sarcomatoid differentiation was associated with a 58% increased risk
      of death from RCC (P < 0.001). For patients with grade 4 non-metastatic (M0) RCC,
      the presence of sarcomatoid differentiation was associated with an 82% increased
      risk of death from RCC (P < 0.001). For patients with sarcomatoid RCC, the 2009
      primary tumour classifications, presence of regional lymph nodes and distant
      metastases, coagulative tumour necrosis, and the amount of sarcomatoid
      differentiation were each significantly associated with death from RCC in a
      multivariate setting. After adjusting for other prognostic variables, each 10%
      increase in the amount of sarcomatoid differentiation was associated with a 6%
      increased risk of death from RCC (P = 0.028). Patients whose tumours contained
      >=30% (median amount) sarcomatoid differentiation were 52% more likely to die
      from RCC compared with patients whose tumours contained <30% sarcomatoid
      differentiation (hazard ratio 1.52; P = 0.018). CONCLUSIONS: Among patients with
      grade 4 RCC, either with or without distant metastases at surgery, sarcomatoid
      differentiation is significantly associated with adverse survival in a
      multivariate setting. We also suggest for the first time that the percentage of
      sarcomatoid differentiation is an independent prognostic feature in a
      multivariate setting. The 2009 primary tumour classifications, regional lymph
      node status, the presence of distant metastases classifications, coagulative
      tumour necrosis, and the amount of sarcomatoid differentiation are independent
      predictors of survival for patients with sarcomatoid RCC.

PMID- 24730413
TI  - A consensus parameter for the evaluation and management of angioedema in the
      emergency department.
AB  - Despite its relatively common occurrence and life-threatening potential, the
      management of angioedema in the emergency department (ED) is lacking in terms of
      a structured approach. It is paramount to distinguish the different etiologies of
      angioedema from one another and more specifically differentiate histaminergic
      mediated angioedema from bradykinin-mediated angioedema, especially in lieu of
      the more novel treatments that have recently become available for bradykinin
      mediated angioedema. With this background in mind, this consensus parameter for
      the evaluation and management of angioedema attempts to provide a working
      framework for emergency physicians (EPs) in approaching the patient with
      angioedema in terms of diagnosis and management in the ED. This consensus
      parameter was developed from a collaborative effort among a group of EPs and
      leading allergists with expertise in angioedema. After rigorous debate, review of
      the literature, and expert opinion, the following consensus guideline document
      was created. The document has been endorsed by the American College of Allergy,
      Asthma & Immunology (ACAAI) and the Society for Academic Emergency Medicine
      (SAEM). 

PMID- 24730417
TI  - 17alpha-Oestradiol-induced neuroprotection in the brain of spontaneously
      hypertensive rats.
AB  - 17beta-oestradiol is a powerful neuroprotective factor for the brain
      abnormalities of spontaneously hypertensive rats (SHR). 17alpha-Oestradiol, a
      nonfeminising isomer showing low affinity for oestrogen receptors, is also
      endowed with neuroprotective effects in vivo and in vitro. We therefore
      investigated whether treatment with 17alpha-oestradiol prevented pathological
      changes of the hippocampus and hypothalamus of SHR. We used 20-week-old male SHR
      with a blood pressure of approximately 170 mmHg receiving s.c. a single 800 MUg
      pellet of 17alpha-oestradiol dissolved in cholesterol or vehicle only for 2 weeks
      Normotensive Wistar-Kyoto (WKY) rats were used as controls. 17alpha-Oestradiol
      did not modify blood pressure, serum prolactin, 17beta-oestradiol levels or the
      weight of the testis and pituitary of SHR. In the brain, we analysed steroid
      effects on hippocampus Ki67+ proliferating cells, doublecortin (DCX) positive
      neuroblasts, glial fibrillary acidic protein (GFAP)+ astrocyte density, aromatase
      immunostaining and brain-derived neurotrophic factor (BDNF) mRNA. In the
      hypothalamus, we determined arginine vasopressin (AVP) mRNA. Treatment of SHR
      with 17alpha-oestradiol enhanced the number of Ki67+ in the subgranular zone and
      DCX+ cells in the inner granule cell layer of the dentate gyrus, increased BDNF
      mRNA in the CA1 region and gyrus dentatus, decreased GFAP+ astrogliosis in the
      CA1 subfield, and decreased hypothalamic AVP mRNA. Aromatase expression was
      unmodified. By contrast to SHR, normotensive WKY rats were unresponsive to
      17alpha-oestradiol. These data indicate a role for 17alpha-oestradiol as a
      protective factor for the treatment of hypertensive encephalopathy. Furthermore,
      17alpha-oestradiol is weakly oestrogenic in the periphery and can be used in
      males.

PMID- 24730419
TI  - Fluorescent visualisation of the hypothalamic oxytocin neurones activated by
      cholecystokinin-8 in rats expressing c-fos-enhanced green fluorescent protein and
      oxytocin-monomeric red fluorescent protein 1 fusion transgenes.
AB  - The up-regulation of c-fos gene expression is widely used as a marker of neuronal
      activation elicited by various stimuli. Anatomically precise observation of c-fos
      gene products can be achieved at the RNA level by in situ hybridisation or at the
      protein level by immunocytochemistry. Both of these methods are time and labour
      intensive. We have developed a novel transgenic rat system that enables the
      trivial visualisation of c-fos expression using an enhanced green fluorescent
      protein (eGFP) tag. These rats express a transgene consisting of c-fos gene
      regulatory sequences that drive the expression of a c-fos-eGFP fusion protein. In
      c-fos-eGFP transgenic rats, robust nuclear eGFP fluorescence was observed in
      osmosensitive brain regions 90 min after i.p. administration of hypertonic
      saline. Nuclear eGFP fluorescence was also observed in the supraoptic nucleus
      (SON) and paraventricular nucleus (PVN) 90 min after i.p. administration of
      cholecystokinin (CCK)-8, which selectively activates oxytocin (OXT)-secreting
      neurones in the hypothalamus. In double transgenic rats that express c-fos-eGFP
      and an OXT-monomeric red fluorescent protein 1 (mRFP1) fusion gene, almost all
      mRFP1-positive neurones in the SON and PVN expressed nuclear eGFP fluorescence 90
      min after i.p. administration of CCK-8. It is possible that not only a plane
      image, but also three-dimensional reconstruction image may identify cytoplasmic
      vesicles in an activated neurone at the same time.

PMID- 24730420
TI  - Umbilical cord-derived mesenchymal stem cells instruct dendritic cells to acquire
      tolerogenic phenotypes through the IL-6-mediated upregulation of SOCS1.
AB  - The mechanisms responsible for the inhibitory effects of mesenchymal stem cells
      (MSCs) on dendritic cells (DCs) are still poorly understood. Our investigation of
      the potential signaling pathways revealed for the first time that human umbilical
      cord-derived MSCs (UC-MSCs) instruct DCs to acquire tolerogenic phenotypes
      through the IL-6-mediated upregulation of SOCS1. This subset of MSC-DCs exhibited
      a tolerogenic pattern, with a clear decrease in the expression of co-stimulatory
      molecules and the capacity to stimulate CD3(+) T cell proliferation and
      inflammatory factor secretion, and a significant increase in the production of
      inhibitory cytokine IL-10 and the ability to induce Treg cells and Th2 responses.
      Adoption of this tolerogenic pattern required the activation of SOCS1, which
      blocked DC maturation by impairing TLR4 signaling. The effects of UC-MSCs on
      SOCS1 activation were essentially mediated by the JAK-STAT pathway via IL-6
      secretion. In summary, our data identify a new mechanism, involving the IL-6
      mediated upregulation of SOCS1, by which UC-MSCs instruct DCs to acquire
      tolerogenic phenotypes. 

PMID- 24730421
TI  - Future directions in research on psychotherapy for adolescent depression.
AB  - Research over the past 3 decades has shown that psychotherapy can successfully
      address adolescent depression. Cognitive behavioral models have been most
      extensively and rigorously tested, with evidence also supporting interpersonal
      psychotherapy and attachment-based family therapy. However, the vast majority of
      studies have focused on short-term treatment of depressive episodes, even as
      evidence accumulates that depression is frequently a recurring condition
      extending into adulthood. Moreover, treatment studies indicate that better longer
      term outcomes are attained by adolescents who respond earlier and more completely
      to intervention. Given what has been learned to date about adolescent depression
      treatment, future psychotherapy research should adopt a longer term perspective
      and focus on the following key challenges: (a) preventing relapse and recurrent
      episodes, while improving speed and thoroughness of initial treatment response;
      (b) identifying the necessary treatment components and learning processes that
      lead to successful and enduring recovery from depression; (c) determining whether
      and, if so, how-to address comorbid disorders within depression treatment; (d)
      addressing the dilemma of simplicity versus complexity in treatment models. Given
      the relatively small number of evidence-based treatment models, newer approaches
      warrant investigation. These should be tested against existing models and also
      compared to medication and combined (psychotherapy plus medication) treatment.
      Advances in technology now enable investigators to improve dissemination, to
      conduct experimental psychotherapeutics and to expand application of Internet
      based interventions to the goals of relapse and recurrence prevention. 

PMID- 24730418
TI  - Sex differences in expression of oestrogen receptor alpha but not androgen
      receptor mRNAs in the foetal lamb brain.
AB  - Gonadal steroid hormones play important roles during critical periods of
      development to organise brain structures that control sexually dimorphic
      neuroendocrine responses and behaviours. Specific receptors for androgens and
      oestrogens must be expressed at appropriate times during development to mediate
      these processes. The present study was performed to test for sex differences in
      the relative expression of oestrogen receptor (ER)alpha and androgen receptor
      (AR) mRNA during the window of time in gestation that is critical for behavioural
      masculinisation and differentiation of the ovine sexually dimorphic nucleus
      (oSDN) in the sheep. In addition, we examined whether ERalpha and AR mRNA
      expression is localised within the nascent oSDN and could be involved in its
      development. Using the quantitative real-time polymerase chain reaction, we found
      that females expressed more ERalpha mRNA than males in medial preoptic area and
      medial basal hypothalamus during the mid-gestational critical period for brain
      sexual differentiation. No sex differences were found for AR mRNA in any tissue
      examined or for ERalpha in amygdala and frontal cortex. Using radioactive in situ
      hybridisation, we found that the distributions of ERalpha and AR mRNA overlapped
      with aromatase mRNA, which delineates the boundaries of the developing oSDN and
      identifies this nucleus as a target for both androgens and oestrogens. These data
      demonstrate that the transcriptional machinery for synthesising gonadal steroid
      receptors is functional in the foetal lamb brain during the critical period for
      sexual differentiation and suggest that possible mechanisms for establishing
      dimorphisms controlled by gonadal steroids may exist at the level of steroid
      hormone receptor expression. 

PMID- 24730422
TI  - Recent decreases in specific interpretation biases predict decreases in
      neuroticism: evidence from a longitudinal study with young adult couples.
AB  - Engaging in a romantic relationship represents one important life experience in
      young adulthood that has been shown to catalyze age-related decrease in
      neuroticism (Neyer & Lehnart, 2007). The current research builds directly on this
      finding by investigating one process that underlies the partnership effect. We
      focused on the relationship-specific interpretation bias (RIB; Finn, Mitte, &
      Neyer, 2013), which is the tendency to interpret ambiguous partner and
      relationship scenarios in a negative way. It was expected that the RIB decreases
      within relationships in young adulthood and that this decrease in turn predicts
      long-term declines in neuroticism. A sample of 245 young adult romantic couples
      was assessed four times across 9 months. Actor and partner effects of changes in
      the RIB on changes in neuroticism were analyzed using a dyadic dual change model.
      Recent time-to-time decreases in the RIB predicted one's own (actor effect)
      decline in neuroticism across 9 months. Similarly, there was a trend for a
      partner effect. We conclude that changes in biased relationship-specific
      interpretations reflect one unique process that contributes to the understanding
      of romantic relationship effects on personality development. 

PMID- 24730424
TI  - Impact of living with pulmonary hypertension: a qualitative exploration.
AB  - Little is known about the impact of living with pulmonary hypertension. This
      paper reports data exploring the experience of living with pulmonary
      hypertension. Qualitative, semistructured, one-to-one interviews were conducted
      in participants' homes to understand their experiences of living with pulmonary
      hypertension. Thematic analysis was used to identify codes and generate themes
      from the interview data. The identification of initial codes was conducted
      independently by the first author, and checked by the second. Thirty patients
      recruited through the pulmonary hypertension descriptions of living with
      pulmonary hypertension are presented under five themes that center on the
      invisibility of pulmonary hypertension, and its complex treatment are presented:
      (i) living with a hidden illness; (ii) being on a symptomology rollercoaster;
      (iii) expectations from treatments; (iv) treatment burden; and (v) awareness of
      financial burden of treatments. Key findings included daily challenges of living
      with a rare condition that is largely "hidden" and its related complex treatment
      regimes. People with pulmonary hypertension would benefit if more healthcare
      professionals, as well as family and friends, would validate their condition and
      provide them with appropriate support. 

PMID- 24730426
TI  - Family-supportive supervisor behaviors, work engagement, and subjective well
      being: a contextually dependent mediated process.
AB  - Grounded in a multistudy framework, we examined the relationship between family
      supportive supervisor behaviors, work engagement, and subjective well-being as a
      contextually dependent mediated process. In Study 1 (N = 310), based on broaden
      and-build and conservation of resources theories, we tested the proposed mediated
      process while controlling for perceived organizational support and perceived
      managerial effectiveness. We also demonstrated that family-supportive supervisor
      behaviors are distinguishable from general supervisor behaviors. In Study 2 (N =
      1,640), using multigroup structural equation modeling, we validated and extended
      Study 1 results by examining how the mediated model varied based on 2
      contextualizing constructs: (a) dependent care responsibilities and (b)
      availability of family-friendly benefits. Although the mediational results were
      contextually dependent, they were not necessarily consistent with hypothesizing
      based on conservation of resources theory. Practical implications are emphasized
      in addition to future research directions.

PMID- 24730425
TI  - Work-family conflict, family-supportive supervisor behaviors (FSSB), and sleep
      outcomes.
AB  - Although critical to health and well-being, relatively little research has been
      conducted in the organizational literature on linkages between the work-family
      interface and sleep. Drawing on conservation of resources theory, we use a sample
      of 623 information technology workers to examine the relationships between work
      family conflict, family-supportive supervisor behaviors (FSSB), and sleep quality
      and quantity. Validated wrist actigraphy methods were used to collect objective
      sleep quality and quantity data over a 1 week period of time, and survey methods
      were used to collect information on self-reported work-family conflict, FSSB, and
      sleep quality and quantity. Results demonstrated that the combination of
      predictors (i.e., work-to-family conflict, family-to-work conflict, FSSB) was
      significantly related to both objective and self-report measures of sleep
      quantity and quality. Future research should further examine the work-family
      interface to sleep link and make use of interventions targeting the work-family
      interface as a means for improving sleep health.

PMID- 24730427
TI  - Work-family enrichment, work-family conflict, and marital satisfaction: a dyadic
      analysis.
AB  - This study was designed to examine whether spouses' work-to-family (WF)
      enrichment experiences account for their own and their partner's marital
      satisfaction, beyond the effects of WF conflict. Data were collected from both
      partners of 215 dual-earner couples with children. As hypothesized, structural
      equation modeling revealed that WF enrichment experiences accounted for variance
      in individuals' marital satisfaction, over and above WF conflict. In line with
      our predictions, this positive link between individuals' WF enrichment and their
      marital satisfaction was mediated by more positive marital behavior, and more
      positive perceptions of the partner's behavior. Furthermore, evidence for
      crossover was found. Husbands who experienced more WF enrichment were found to
      show more marital positivity (according to their wives), which related to
      increased marital satisfaction in their wives. No evidence of such a crossover
      effect from wives to husbands was found. The current findings not only highlight
      the added value of studying positive spillover and crossover effects of work into
      the marriage, but also suggest that positive spillover and crossover effects on
      marital satisfaction might be stronger than negative spillover and crossover are.
      These results imply that organizational initiatives of increasing job enrichment
      may make employees' marital life happier and can contribute to a happy, healthy,
      and high-performing workforce.

PMID- 24730428
TI  - Development of perceived job insecurity across two years: associations with
      antecedents and employee outcomes.
AB  - This 2-year longitudinal study among 848 university employees investigated the
      individual development of perceived job insecurity (JI) in the context of changes
      occurring in the Finnish universities during the follow-up time. Adopting a
      person-oriented approach through latent profile analysis, 8 classes of employees
      with similar mean levels and mean-level changes in JI were identified. Two of
      these classes (75% of the participants) indicated stable (low, moderately high)
      JI, and the remaining 6 classes (25% of the participants) showed change
      (decreasing, increasing, curvilinear) in the level of JI across time. We then
      examined possible differences between these classes with respect to individual
      antecedents and outcomes of JI. Of the antecedents, the type of employment
      contract distinguished best between the JI classes. Of the outcomes, moderately
      high stable JI was associated with low stable vigor and high stable levels of
      exhaustion and turnover intentions across time. In addition, it seemed that a
      decrease in JI was associated with a decrease in exhaustion and turnover
      intentions and vice versa. Altogether the findings suggest that developmental JI
      classes exhibit a substantial amount of heterogeneity, which is simultaneously
      reflected in occupational well-being.

PMID- 24730429
TI  - Healthy eating at different risk levels for job stress: testing a moderated
      mediation.
AB  - Health behavior, like fruit and vegetable consumption (FVC), is affected by
      unfavorable job conditions. However, there is little research to date that
      combines job stress models and health-behavior change models. This longitudinal
      study examined the contribution of risk factors associated with job stress to the
      intention-planning-FVC relationship. In the context of the Health Action Process
      Approach, action planning (when-where-how plans) and coping planning (plans to
      overcome anticipated barriers) have been shown to be successful mediators in the
      translation of health-related intentions into action. Risk factors for job stress
      are operationalized as the interaction of job demands and job resources in line
      with the Job Demands-Resources (JD-R) model. Two hundred seventy-two employees
      (mean age 41.2 years, 73.9% female) from different jobs completed measures of
      intention at baseline (t1), action planning and coping planning 2 weeks later
      (t2), and FVC another 2 weeks later (t3). Job demands and job resources were
      assessed at t1 and t2. A moderated mediation analysis indicated that risk factors
      for job stress moderate the translation of intention into action planning (B = 
      0.23, p < .05) and coping planning (B = -0.14, p < .05). No moderation effect of
      the planning-FVC relationship by risk factors for job stress was found. However,
      coping planning directly predicted FVC (B = 0.36, p < .001). Findings suggest
      that employees intending to eat healthily use action planning and coping planning
      when job demands exceed job resources. For increasing FVC, coping planning
      appears most beneficial.

PMID- 24730430
TI  - Estimating the precision of disc diffusion antibiotic susceptibility data
      published by the European committee on antimicrobial susceptibility testing.
AB  - Analysis of 163 disc diffusion data sets, 115 for bacterial species groups and 48
      for types strains, published by EUCAST, was used to optimize the setting of the
      parameters of a standardized protocol for normalized resistance interpretation of
      these data. The standard deviations of the normalized distributions of these data
      sets, calculated using this standardized protocol, were shown to be independent
      of the means of their respective distributions. These standard deviations could,
      therefore, be used as a metric to quantify the precision of disc diffusion data
      sets. The median value of the standard deviations for 115 EUCAST data sets
      produced in multiple laboratory studies of bacterial species groups was 2.3 mm
      and that for the 48 EUCAST data sets produced in multiple laboratory studies of
      type strains was 1.5 mm. It is argued that this standardized method for
      estimating the precision of disc diffusion data provides a tool by which
      individual laboratories can assess the quality of the disc diffusion data they
      produce. 

PMID- 24730431
TI  - Directly acting antivirals (DAAs) for the treatment of chronic hepatitis C virus
      infection in liver transplant patients: "a flood of opportunity".
AB  - Chronic hepatitis C virus (HCV) is the leading cause of liver transplantation
      (LT) in adults. However, infection of the allograft is universal and associated
      with reduced graft and patient survival. Although successful eradication improves
      posttransplant outcome, current antiviral therapies have poor efficacy and
      tolerability. Direct acting antiviral agents (DAAs) provide new opportunities for
      treatment of HCV recurrence. The addition of a first-generation NS3/4A protease
      inhibitor (PI) has increased the efficacy of pegylated interferon and ribavirin
      in patients with chronic HCV genotype 1 infection. Preliminary efficacy results
      from open-labeled studies of PI-based triple therapy in LT recipients are
      encouraging. However, the tolerability of triple therapy is reduced following LT,
      because of increased anemia and drug-drug interactions. The use of PI-based
      triple therapy in LT recipients seems best suited to larger centers, experienced
      with management of PI toxicity. Fortunately, other classes of DAAs targeting
      different steps of HCV replication are in clinical trials, including nucleotide
      polymerase (NUC-NS5B) inhibitors, nonnucleotide polymerase (non-NUC-NS5B)
      inhibitors and NS5A inhibitors. Several dual and triple DAA regimens are in
      clinical development. Phase II studies conducted in patients before and after LT
      suggest that these regimens will dramatically reduce the impact of recurrent HCV.
      There is a tide in the affairs of men. Which, taken at the flood, leads on to
      fortune (Shakespeare: J Caesar Act 4, scene 3). 

PMID- 24730432
TI  - Severe laminitis in multiple zoo species.
AB  - A 10-year record review from a zoological institution in the western USA
      identified four cases of severe laminitis resulting in rotation and protrusion of
      the third phalanx through the sole. Laminitis is reported in a Masai giraffe
      (Giraffa camelopardalis tippelskirchi), a Sichuan takin (Budorcas taxicolor
      tibetana), a greater Malayan chevrotain (Tragulus napu) and a giant eland
      (Taurotragus derbianus). This is the first report of severe laminitis with pedal
      bone rotation and protrusion in multiple species of non-domestic hoofstock, and
      the first report of this disease in three of these species (takin, chevrotain,
      and giant eland). 

PMID- 24730433
TI  - Doubling the efficiency of third harmonic generation by positioning ITO
      nanocrystals into the hot-spot of plasmonic gap-antennas.
AB  - We incorporate dielectric indium tin oxide nanocrystals into the hot-spot of gold
      nanogap-antennas and perform third harmonic spectroscopy on these hybrid
      nanostructure arrays. The combined system shows a 2-fold increase of the radiated
      third harmonic intensity when compared to bare gold antennas. In order to
      identify the origin of the enhanced nonlinear response we perform finite element
      simulations of the nanostructures, which are in excellent agreement with our
      measurements. We find that the third harmonic signal enhancement is mainly
      related to changes in the linear optical properties of the plasmonic antenna
      resonances when the ITO nanocrystals are incorporated. Furthermore, the dominant
      source of the third harmonic is found to be located in the gold volume of the
      plasmonic antennas. 

PMID- 24730434
TI  - Composite films of poly(3-hexylthiophene) grafted single-walled carbon nanotubes
      for electrochemical detection of metal ions.
AB  - In this study, we prepared electrochemically active films of poly(3
      hexylthiophene) grafted single-walled carbon nanotubes (SWNT-g-P3HT) by using a
      modified vacuum-assisted deposition approach, in which a SWNT-g-P3HT composite
      layer of various thicknesses was deposited on the top of a thin SWNT layer.
      Measurement of the optical and electrical properties of the SWNT-g-P3HT composite
      films demonstrated that the thickness of the SWNT-g-P3HT composite films was
      controllable. The data of transmission electron microscope observation and Raman
      spectroscopy indicated that the covalent grafting of P3HT onto the surfaces of
      SWNTs resulted in intimate and stable connectivity between the two components in
      the SWNT-g-P3HT composite. Capitalizing on these unique features, we successfully
      developed a new class of electrochemical sensors that used the SWNT-g-P3HT
      composite films deposited on an indium-tin oxide substrate as an electrochemical
      electrode for detection of metal ions. Significantly, such a SWNT-g-P3HT
      composite electrode showed advantages in selective, quantitative, and more
      sensitive detection of Ag(+) ions. 

PMID- 24730435
TI  - Physiotherapists can identify female football players with high knee valgus
      angles during vertical drop jumps using real-time observational screening.
AB  - STUDY DESIGN: Clinical measurement, controlled laboratory study. OBJECTIVES: To
      assess the relationships among real-time observational screening of frontal plane
      knee control and knee valgus angles and abduction moments calculated from 3-D
      motion analysis during a vertical drop jump. A secondary purpose was to
      investigate interrater agreement for 3 independent physiotherapists. BACKGROUND:
      Current approaches to screen for anterior cruciate ligament injury risk are based
      on complex biomechanical analyses or 2-dimensional video reviews. There is a need
      for simple and efficient, low-cost screening methods. METHODS: Sixty Norwegian
      elite female football (soccer) players performed a vertical drop-jump task. Using
      real-time observational screening, 3 physiotherapists independently scored each
      participant's frontal plane knee control as good, reduced, or poor, based on
      specific criteria. Screening test scores were correlated to frontal plane knee
      kinematics and kinetics using 3-D motion analysis. Interrater agreement was
      determined using kappa correlation coefficients. RESULTS: Knee valgus angles
      differed significantly among players rated as having poor, reduced, or good knee
      control (10.3 degrees  +/- 3.4 degrees , 5.4 degrees  +/- 4.1 degrees , and 1.9
      degrees  +/- 4.3 degrees , respectively). The correlation between the observation
      test scores and valgus angles was moderate for all raters (0.54-0.60, P<=.001),
      but the observation scores correlated poorly with abduction moments (0.09-0.11,
      P>.05). The highest discriminative accuracy was found for knee valgus angles
      across all raters (area under the receiver-operating-characteristic curve, 0.85
      0.89). The interrater agreement between the physiotherapists was substantial to
      almost perfect, with percentage agreement and kappa coefficients ranging from 70%
      to 95% and 0.52 to 0.92, respectively. CONCLUSION: Physiotherapists can reliably
      identify female athletes with high knee valgus angles in a vertical drop-jump
      landing using real-time observational screening.

PMID- 24730436
TI  - Physical dysfunction and nonorganic signs in patients with chronic neck pain:
      exploratory study into interobserver reliability and construct validity.
AB  - STUDY DESIGN: Repeated-measurement design. OBJECTIVES: To explore interobserver
      reliability of the modified physical dysfunction severity (mPDS) as a measure for
      impairment of the cervical spine and the modified cervical nonorganic signs
      (mcNOS) as a measure for behavioral signs, and to explore construct validity of
      the mPDS and mcNOS. BACKGROUND: The PDS has been used for evaluation of treatment
      efficacy in controlled trials in primary care. The cervical nonorganic signs were
      developed to assess illness behavior in patients with neck pain. METHODS: Two
      observers independently assessed the mPDS and mcNOS in 51 patients with chronic
      neck pain in an outpatient tertiary rehabilitation setting, with a 3-week
      interval between assessments. Interobserver reliability for total scores of the
      mPDS and mcNOS was expressed as an intraclass correlation coefficient.
      Interobserver agreement for individual mcNOS tests was calculated as absolute
      agreement and Cohen kappa. Construct validity was expressed as Spearman
      correlation between the mPDS and mcNOS with the Neck Pain and Disability Scale
      and numeric pain rating scale for pain. RESULTS: The interobserver reliability of
      the mPDS and mcNOS had intraclass correlation coefficients of 0.72 and 0.78,
      respectively. Agreement for individual mcNOS tests ranged from 63% to 88%, and
      kappa values ranged from 0.14 to 0.54. Correlation with the Neck Pain and
      Disability Scale was 0.26 for the mPDS and 0.49 for the mcNOS, and the
      correlation with the numeric pain rating scale was 0.32 for the mPDS and 0.37 for
      the mcNOS. CONCLUSION: Interobserver reliability of both the mPDS and mcNOS was
      acceptable. The interobserver agreement for the individual mcNOS tests ranged
      from poor to acceptable. Construct validity of the mPDS and mcNOS appeared
      satisfactory.

PMID- 24730437
TI  - Neurodynamic responses to the femoral slump test in patients with anterior knee
      pain syndrome.
AB  - STUDY DESIGN: Matched-control, cross-sectional study. OBJECTIVES: The purpose of
      this study was to compare the responses to the femoral slump test (FST),
      including the change in hip range of motion and level of discomfort, between
      subjects with and without anterior knee pain. BACKGROUND: Anterior knee pain
      syndrome is a common problem among adults. The FST is the neurodynamic test used
      to assess the mechanosensitivity of the femoral component of the nervous system.
      However, as of yet, there is no literature discussing the use of the FST in
      patients with anterior knee pain. METHODS: Thirty patients with anterior knee
      pain and 30 control participants, matched by gender, age, and dominant leg, were
      recruited. The subjects received the FST, during which the hip extension angle
      and the location and intensity of pain/discomfort were recorded. Reproduction of
      symptoms that were alleviated by neck extension was interpreted as a positive
      test. Differences in hip extension angle and pain intensity between groups were
      examined using a 2-way, repeated-measures analysis of variance and a Kruskal
      Wallis analysis. The level of significance was set at alpha = .05. RESULTS:
      Subjects with anterior knee pain had a smaller hip extension angle than that of
      controls (-3.6 degrees  +/- 5.3 degrees  versus 0.6 degrees  +/- 6.1 degrees ;
      mean difference, 4.2 degrees ; 95% confidence interval [CI]: 1.24 degrees , 7.15
      degrees ; P = .006). Eight patients with anterior knee pain showed a positive
      FST, and those with a positive FST had a smaller hip extension angle (-5.7
      degrees  +/- 4.5 degrees ) than that of controls (mean difference, 6.3 degrees ;
      95% CI: 0.8 degrees , 11.8 degrees ; P = .007). There was no difference in the
      hip extension angle between the positive and negative FST groups (mean
      difference, 2.9 degrees ; 95% CI: -8.5 degrees , 2.0 degrees ) or between the
      negative FST and control groups (mean difference, 3.4 degrees ; 95% CI: -0.4
      degrees , 7.3 degrees ). CONCLUSION: Results of this study suggest that altered
      mechanosensitivity of the femoral nerve occurred in the patients with anterior
      knee pain who presented with a positive FST. The role of increased
      mechanosensitivity in the development and management of anterior knee pain should
      be investigated in the future.

PMID- 24730438
TI  - Antibiotic releasing biodegradable scaffolds for osteomyelitis.
AB  - Osteomyelitis is characterized by progressive inflammatory bone degeneration. In
      the management of chronic osteomyelitis, it is necessary to remove the infected
      bone tissue followed by implantation of an antibiotic releasing biomaterial that
      can release antibiotic locally for long periods of time. The main carrier used in
      clinics for this application is polymethylmethacrylate (PMMA) (Eg. Septopal
      beads). However, major drawback is the need of an additional surgery to remove
      the beads after therapy, as PMMA is not biodegradable. This necessitates the
      requirement of biodegradable carrier systems that can release antibiotics and
      simultaneously support debrided bone formation. This review summarizes
      biodegradable carrier systems that have been reported for the localised treatment
      and prophylaxis of osteomyelitis. 

PMID- 24730439
TI  - Design and development of oral nanoparticulated insulin in multiple emulsion.
AB  - The present research aimed at developing an injection-free nanoparticulated
      formulation in multiple emulsion form, for oral delivery of insulin, which
      otherwise undergoes degradation in the gastric environment if administered
      orally. Insulin-polymeric nanoparticles were prepared using layer by layer (LbL)
      adsorption method and incorporated into an emulsion to form a nanoparticulated
      multiple emulsion. Using 0.6 M sodium chloride, the insulin nanoaggregates of 300
      400 nm size were obtained about a yield of 94%. The characteristics of a
      representative nanoparticle were as follows: particle size - 391.9+/-0.41 nm,
      polydispersity index -0.425, zeta potential- +20.6 mv, encapsulation efficiency-
      86.7+/-1.42% and percentage entrapment efficiency of the insulin-polymeric
      nanoparticles in the inner aqueous phase of emulsion was 84.6%. The FT-IR
      analysis confirms that there were no drug interactions with the polymers.
      Stability analysis carried out for 3 months at 8-40  degrees C, showed only minor
      changes at the end period. The release kinetics of the nanoparticulated multiple
      emulsion at pH 7.4 followed first order kinetics and obeyed the Fickian law.
      However, at pH 2.0 the release kinetics from nanoparticulated multiple emulsion
      followed zero order kinetics without obeying to the Fickian law. In conclusion,
      our data demonstrate that the nanoparticulated multiple emulsion formulation has
      good release characteristics and imparted a tolerable protection for insulin at
      different pH conditions, which may be exploited for oral administration. 

PMID- 24730440
TI  - Formulation and evaluation of gastroretentive microballoons containing baclofen
      for a floating oral controlled drug delivery system.
AB  - The objective of the present study was to fabricate and evaluate a
      multiparticulate oral gastroretentive dosage form of baclofen characterized by a
      central large cavity (hollow core) promoting unmitigated floatation with
      practical applications to alleviate the signs and symptoms of spasticity and
      muscular rigidity. Solvent diffusion and evaporation procedure were applied to
      prepare floating microspheres with a central large cavity using various
      combinations of ethylcellulose (release retardant) and HPMC K4M (release
      modifier) dissolved in a mixture of dichloromethane and methanol (2:1). The
      obtained microspheres (700-1000 um) exhibit excellent floating ability (86 +/-
      2.00%) and release characteristics with entrapment efficiency of 95.2 +/- 0.32%.
      Microspheres fabricated with ethylcellulose to HPMC K4M in the ratio 8.5:1.5
      released 98.67% of the entrapped drug in 12 h. Muscle relaxation caused by
      baclofen microspheres impairs the rotarod performance for more than 12 h.
      Abdominal X-ray images showed that the gastroretention period of the floating
      barium sulfate- labeled microspheres was no less than 10 h. The buoyant baclofen
      microspheres provide a promising gastroretentive drug delivery system to deliver
      baclofen in spastic patients with a sustained release rate.

PMID- 24730441
TI  - Cytokeratin 7/19 expression in N-diethylnitrosamine-induced mouse hepatocellular
      lesions: implications for histogenesis.
AB  - Hepatocellular carcinoma (HCC) is a common malignancy with poor clinical outcome,
      whose histogenesis is the subject of intense debate. Specifically, expression of
      cytokeratins (CKs) 7 and 19, associated with aggressive biological behaviour, is
      proposed to reflect a possible progenitor cell origin or tumour dedifferentiation
      towards a primitive phenotype. This work addresses that problem by studying CKs 7
      and 19 expression in N-diethylnitrosamine (DEN)-induced mouse HCCs. ICR mice were
      divided into six DEN-exposed and six matched control groups. Samples were taken
      from each group at consecutive time points. Hyperplastic foci (13 lesions)
      occurred at 29-40 weeks (groups 8, 10 and 12) with diffuse dysplastic areas (19
      lesions) and with one hepatocellular adenoma (HCA) (at 29 weeks). HCCs (4
      lesions) were observed 40 weeks after the first DEN administration (group 12).
      CKs 7 and 19 showed identical expression patterns and located to large, mature
      hepatocytes, isolated or in small clusters. Hyperplastic foci and the single HCA
      were consistently negative for both markers, while dysplastic areas and HCCs were
      positive. These results support the hypothesis that CKs 7 and 19 expression in
      hepatocellular malignancies results from a dedifferentiation process rather than
      from a possible progenitor cell origin. 

PMID- 24730442
TI  - Phenotypic and in vivo functional characterization of immortalized human fetal
      liver cells.
AB  - We report the establishment and characterization of immortalized human fetal
      liver progenitor cells by expression of the Simian virus 40 large T (SV40 LT)
      antigen. Well-characterized cells at various passages were transplanted into nude
      mice with acute liver injury and tested for functional capacity. The SV40LT
      antigen-immortalized fetal liver cells showed a morphology similar to primary
      cells. Cultured cells demonstrated stable phenotypic expression in various
      passages, of hepatic markers such as albumin, CK 8, CK18, transcription factors
      HNF-4alpha and HNF-1alpha and CYP3A/7. The cells did not stain for any of the
      tested cancer-associated markers. Albumin, HNF-4alpha and CYP3A7 expression was
      confirmed by reverse transcription polymerase chain reaction (RT-PCR). Flow
      cytometry showed expression of some progenitor cell markers. In vivo study showed
      that the cells expressed both fetal and differentiated hepatocytes markers. Our
      study suggests new approaches to expand hepatic progenitor cells, analyze their
      fate in animal models aiming at cell therapy of hepatic diseases.

PMID- 24730444
TI  - Construction of divergent fused heterocycles via an acid-promoted intramolecular
      ipso-Friedel-Crafts alkylation of phenol derivatives.
AB  - Two different cascade cyclization processes were developed using aryl group
      substituted propargyl alcohol derivatives with a p-hydroxybenzylamine unit as
      common substrates. Using TFA as an acid promoter, an intramolecular ipso-Friedel
      Crafts alkylation of phenol derivatives, formation of an iminium cation via a
      rearomatization-promoted C-C bond cleavage, an aza-Prins reaction, and a 6
      membered ring formation proceeded sequentially, producing a variety of fused
      tricyclic dihydroquinoline derivatives in 45-99% yield. In addition, a one-pot
      sequential silver acetate-catalyzed hydroamination/etherification-acid-promoted
      skeletal rearrangement was examined using the same series of substrates,
      affording fused-tricyclic indole/benzofuran derivatives in 66-89% yield. 

PMID- 24730443
TI  - Analysis of CD4+ CD8+ double-positive T cells in blood, cerebrospinal fluid and
      multiple sclerosis lesions.
AB  - T cells with a CD4(+) CD8(+) double-positive (DP) phenotype are present in small
      numbers in the peripheral blood of healthy humans and may have anti-viral
      capacities. Here we investigate numbers and function of DP T cells in patients
      with relapsing-remitting multiple sclerosis (MS), either treatment-naive or under
      therapy with natalizumab. Flow cytometry analysis revealed that frequencies of
      circulating DP T cells in treatment-naive and natalizumab-treated MS patients are
      comparable to healthy controls. These cells have a memory phenotype with
      cytotoxic potential, express high levels of CD49d and are similarly functional in
      treatment-naive as well as natalizumab-treated MS patients. DP T cells were
      enriched in the cerebrospinal fluid, but do not invade acutely inflamed MS
      lesions. In conclusion, DP T cells are functional in MS and may play a role in
      the immune surveillance of the central nervous system, but do not display
      functional impairment under natalizumab therapy. 

PMID- 24730445
TI  - Microbial abundance and community composition influence production performance in
      a low-temperature petroleum reservoir.
AB  - Enhanced oil recovery using indigenous microorganisms has been successfully
      applied in the petroleum industry, but the role of microorganisms remains poorly
      understood. Here, we investigated the relationship between microbial population
      dynamics and oil production performance during a water flooding process coupled
      with nutrient injection in a low-temperature petroleum reservoir. Samples were
      collected monthly over a two-year period. The microbial composition of samples
      was determined using 16S rRNA gene pyrosequencing and real-time quantitative
      polymerase chain reaction analyses. Our results indicated that the microbial
      community structure in each production well microhabitat was dramatically altered
      during flooding with eutrophic water. As well as an increase in the density of
      microorganisms, biosurfactant producers, such as Pseudomonas, Alcaligenes,
      Rhodococcus, and Rhizobium, were detected in abundance. Furthermore, the density
      of these microorganisms was closely related to the incremental oil production.
      Oil emulsification and changes in the fluid-production profile were also
      observed. In addition, we found that microbial community structure was strongly
      correlated with environmental factors, such as water content and total nitrogen.
      These results suggest that injected nutrients increase the abundance of
      microorganisms, particularly biosurfactant producers. These bacteria and their
      metabolic products subsequently emulsify oil and alter fluid-production profiles
      to enhance oil recovery. 

PMID- 24730446
TI  - Antidiabetic plants improving insulin sensitivity.
AB  - BACKGROUND: Globally, the prevalence of diabetes mellitus is increasing at an
      alarming rate. This chronic pathology gravely troubled the human health and
      quality of life. Both insulin deficiency and insulin resistance are involved in
      the pathophysiology of diabetes mellitus. Moreover, insulin resistance is being
      diagnosed nowadays in a growing population of diabetic and obese patients,
      especially in industrialized societies. There are lots of conventional agents
      available to control and to treat diabetes, but total recovery from this disorder
      has not been reported up to this date. Plants provided a potential source of
      hypoglycemic drugs and are widely used in several traditional systems of medicine
      to prevent diabetes. A few reviews with less attention paid to mechanisms of
      action have been published on antidiabetic plants. OBJECTIVES: The present review
      focuses on the various plants that have been reported to be effective in
      improving insulin sensitivity associated with diabetes. KEY FINDINGS: In this
      work, an updated systematic review of the published literature has been conducted
      to review the antidiabetic plants improving insulin sensitivity and 111 medicinal
      plants have been reported to have a beneficial effect on insulin sensitivity
      using several in-vitro and in-vivo animal models of diabetes. CONCLUSION: The
      different metabolic and cellular effects of the antidiabetic plants improving
      insulin sensitivity are reported indicating the important role of medicinal
      plants as potential alternative or complementary use in controlling insulin
      resistance associated with diabetes mellitus.

PMID- 24730447
TI  - Dual visible light photoredox and gold-catalyzed arylative ring expansion.
AB  - A combination of visible light photocatalysis and gold catalysis is applied to a
      ring expansion-oxidative arylation reaction. The reaction provides an entry into
      functionalized cyclic ketones from the coupling reaction of alkenyl and allenyl
      cycloalkanols with aryl diazonium salts. A mechanism involving generation of an
      electrophilic gold(III)-aryl intermediate is proposed on the basis of mechanistic
      studies, including time-resolved FT-IR spectroscopy. 

PMID- 24730448
TI  - Nanotechnology applications in urology: a review.
AB  - The objectives of this review are to discuss the current literature and summarise
      some of the promising areas with which nanotechnology may improve urological
      care. A Medline literature search was performed to elucidate all relevant studies
      of nanotechnology with specific attention to its application in urology.
      Urological applications of nanotechnology include its use in medical imaging,
      gene therapy, drug delivery, and photothermal ablation of tumours. In vitro and
      animal studies have shown initial encouraging results. Further study of
      nanotechnology for urological applications is warranted to bridge the gap between
      preclinical studies and translation into clinical practice, but nanomedicine has
      shown significant potential to improve urological patient care. 

PMID- 24730449
TI  - Peer victimization in middle childhood impedes adaptive responses to stress: a
      pathway to depressive symptoms.
AB  - Although associations between peer victimization in childhood and later
      psychopathology are well documented, surprisingly little research directly
      examines pathways accounting for these enduring effects. The present study
      addresses this issue by examining whether maladaptive responses to peer
      aggression (less effortful engagement coping and more involuntary responses)
      mediate associations between peer victimization and later depressive symptoms.
      Data were collected on 636 children (338 girls, 298 boys; M = 8.94 years, SD =
      .37) for three consecutive years beginning in 3rd grade. Findings supported the
      proposition that peer victimization predicts lower levels of effortful engagement
      coping and higher levels of involuntary engagement and disengagement responses to
      stress. Moreover, these responses to stress helped to explain the link between
      3rd-grade peer victimization and 5th-grade depressive symptoms. No sex
      differences in these linkages emerged. These findings build on prior theory and
      research by providing a more nuanced understanding of how and why peer
      victimization serves as an early risk factor for depressive symptoms.

PMID- 24730450
TI  - Aspirin treatment improved mesenchymal stem cell immunomodulatory properties via
      the 15d-PGJ2/PPARgamma/TGF-beta1 pathway.
AB  - Bone marrow mesenchymal stem cells (BMMSCs) have been used to treat a variety of
      autoimmune diseases in clinics. However, the therapeutic effects are largely
      dependent on the immunomodulatory capacity of culture-expanded BMMSCs. In the
      present study, we show that aspirin (acetylsalicylic acid, ASA)-treated BMMSCs
      have significantly improved immunomodulatory function, as indicated by
      upregulation of regulatory T cells (Tregs) and downregulation of Th17 cells via
      the 15d-PGJ2/PPARgamma/TGF-beta1 pathway. Furthermore, the therapeutic effect of
      ASA-pretreated BMMSCs was confirmed in a dextran sodium sulfate-induced
      experimental colitis mouse model, in which systemic infusion of ASA-pretreated
      BMMSCs significantly ameliorated disease activity index and colonic inflammation,
      along with an increased number of Tregs and decreased number of Th17 cells. Taken
      together, our results suggest that aspirin treatment is a feasible strategy to
      promote BMMSC-based immunomodulation. 

PMID- 24730453
TI  - Survival after cutaneous melanoma in kidney transplant recipients: a population
      based matched cohort study.
AB  - Transplant recipients are at elevated risk of melanoma and may have poorer
      outcomes than nontransplant recipients. We conducted a national, population
      based, matched cohort study of Australian kidney transplant recipients and
      randomly selected members of the general population matched for age, sex, state
      and year of diagnosis with invasive cutaneous melanoma (1982-2003). Melanoma
      histopathological characteristics were extracted from cancer registry
      notifications and death data were obtained from the National Death Index (1982
      2011). Histopathology was compared using conditional logistic regression and
      overall survival analyzed using Cox proportional hazard models. Compared to
      melanomas in nontransplant recipients (n = 202), melanomas in transplant
      recipients (n = 75) had a higher Clark's level (p = 0.007) and higher American
      Joint Committee on Cancer pathologic stage (p = 0.002), but not Breslow thickness
      (p = 0.11). Posttransplant melanoma conferred higher risk of death (adjusted
      hazard ratio 4.26, 95% CI 2.71-6.72, p < 0.001) after adjustment for the matching
      variables, pathologic stage, histological type and anatomic site. This was not
      explained by transplantation alone. Melanomas in transplant recipients are more
      invasive than those in nonrecipients. More aggressive tumor behavior is also
      supported by a markedly poorer outcome. Treatment algorithms developed for the
      general population with melanoma may not apply to transplant recipients. A review
      of patient education and skin cancer screening guidelines is warranted.

PMID- 24730452
TI  - Acute kidney injury in rats with or without pre-existing chronic kidney disease:
      cytokine/chemokine response.
AB  - AIM: Evidence suggests the possibility that pre-existing chronic kidney (CKD)
      disease may result in a more severe outcome of acute kidney injury (AKI). The aim
      of this study was to examine whether CKD enhances the inflammatory response in
      the kidney, as well as other organs, in response to AKI in rats. METHODS: CKD was
      induced by 5/6 nephrectomy (Nx) and AKI by intestinal ischaemia and reperfusion
      (IIR). RESULTS: For 6 weeks following Nx there was a progressive increase in
      serum creatinine with associated development of albuminuria. The increment in
      creatinine above baseline determination 90 min following IIR was comparable in
      5/6 Nx and in the sham 5/6 Nx. Similarly, increased levels of serum alanine
      transaminase and histomorphological changes in the lungs were observed in the
      rats exposed to IIR compared with those exposed to sham IIR, with no additional
      significant impact of 5/6 Nx. In kidney tissue the levels of cytokines/chemokines
      were equally elevated regardless of exposure to sham IIR or IIR. In lung and
      liver tissue the levels of cytokines/chemokines were equally elevated in the rats
      that were exposed to IIR, regardless of exposure to sham Nx or Nx. CONCLUSION: We
      conclude that the immediate severity of AKI induced by IIR in rats with CKD is
      similar to that induced in rats without CKD. However, the impact of Nx on the
      cytokine/chemokine response after AKI is not uniform in kidney, lung or liver
      tissue.

PMID- 24730454
TI  - LSPR chip for parallel, rapid, and sensitive detection of cancer markers in
      serum.
AB  - Label-free biosensing based on metallic nanoparticles supporting localized
      surface plasmon resonances (LSPR) has recently received growing interest (Anker,
      J. N., et al. Nat. Mater. 2008, 7, 442-453). Besides its competitive sensitivity
      (Yonzon, C. R., et al. J. Am. Chem. Soc. 2004, 126, 12669-12676; Svendendahl, M.,
      et al. Nano Lett. 2009, 9, 4428-4433) when compared to the surface plasmon
      resonance (SPR) approach based on extended metal films, LSPR biosensing features
      a high-end miniaturization potential and a significant reduction of the
      interrogation device bulkiness, positioning itself as a promising candidate for
      point-of-care diagnostic and field applications. Here, we present the first,
      paralleled LSPR lab-on-a-chip realization that goes well beyond the state-of-the
      art, by uniting the latest advances in plasmonics, nanofabrication,
      microfluidics, and surface chemistry. Our system offers parallel, real-time
      inspection of 32 sensing sites distributed across 8 independent microfluidic
      channels with very high reproducibility/repeatability. This enables us to test
      various sensing strategies for the detection of biomolecules. In particular we
      demonstrate the fast detection of relevant cancer biomarkers (human alpha-feto
      protein and prostate specific antigen) down to concentrations of 500 pg/mL in a
      complex matrix consisting of 50% human serum. 

PMID- 24730455
TI  - Vitamin C protects rat cerebellum and encephalon from oxidative stress following
      exposure to radiofrequency wave generated by a BTS antenna model.
AB  - Radio frequency wave (RFW) generated by base transceiver station has been
      reported to produce deleterious effects on the central nervous system function,
      possibly through oxidative stress. This study was conducted to evaluate the
      effect of RFW-induced oxidative stress in the cerebellum and encephalon and the
      prophylactic effect of vitamin C on theses tissues by measuring the antioxidant
      enzymes activity, including: glutathione peroxidase, superoxide dismutase,
      catalase, and malondialdehyde (MDA). Thirty-two adult male Sprague-Dawley rats
      were randomly divided into four equal groups. The control group; the control
      vitamin C group received L-ascorbic acid (200 mg/kg of body weight/day by gavage)
      for 45 days. The RFW group was exposed to RFW and the RFW+ vitamin C group was
      exposed to RFW and received vitamin C. At the end of the experiment, all groups
      were killed and encephalon and cerebellum of all rats were removed and stored at 
      70  degrees C for measurement of antioxidant enzymes activity and MDA. The
      results indicate that exposure to RFW in the test group decreased antioxidant
      enzymes activity and increased MDA compared with the control groups (p < 0.05).
      The protective role of vitamin C in the treated group improved antioxidant
      enzymes activity and reduced MDA compared with the test group (p < 0.05). It can
      be concluded that RFW causes oxidative stress in the brain and vitamin C improves
      the antioxidant enzymes activity and decreases MDA.

PMID- 24730456
TI  - Immune responses to Campylobacter (C. jejuni or C. coli) infections: a two-year
      study of US forces deployed to Thailand.
AB  - Campylobacter spp. is a leading cause of diarrheal disease among US troops
      deployed to Thailand for exercise. We investigated the importance of
      immunological analysis and immune responses against Campylobacter infection in US
      troops deployed to Thailand. Blood and fecal samples were collected from
      volunteered soldiers with diarrhea and from healthy controls. Stool culture was
      performed to identify the pathogens. Campylobacter-specific antibodies, antibody
      secreting cells and cytokines were measured. Several bacterial protein fragments
      in the outer membrane extract of Campylobacter spp., were identified by an
      immunoblot analysis with plasma and fecal antibodies. Among all of the diarrheal
      cases, 35% were Campylobacter-positive. Based on antibody titers in plasma and in
      fecal extract and antibody secreting cells: 6% of healthy controls, 32% of the
      Campylobacter culture-negative diarrheal cases, and 85% of the Campylobacter
      culture-positive diarrheal cases were positive for Campylobacter. Our results
      indicate that the measurement of Campylobacter-specific antibodies in plasma and
      fecal extract samples is a good marker of exposure to Campylobacter, and this
      test may be a useful diagnostic tool for seroepidemiological studies. Elicited
      antibodies against several bacterial outer membrane protein fragments suggest
      that these protein fragments are vital in providing protective immunity against
      Campylobacter. 

PMID- 24730457
TI  - Radiotherapy in fascial fibromatosis: a case series, literature review and
      considerations for treatment of early-stage disease.
AB  - INTRODUCTION: Palmar and plantar fascial fibromatoses are benign
      hyperproliferative disorders of the deep fascia of the palm and sole. This study
      seeks to examine the role of radiotherapy in the management of fascial
      fibromatosis. METHOD: Six consecutive cases of early-stage fascial fibromatosis
      treated with radiotherapy at the Adelaide Radiotherapy Centre between July 2008
      and May 2011 were analysed. The results of the case series were compared with a
      systematic review of the literature. RESULTS: All six cases regressed or showed a
      reduction of symptoms following radiotherapy. Treatment was well tolerated with
      minor toxicities. Median follow-up for the case series was 38.5 months. The
      systematic review identified seven studies describing the use of radiotherapy as
      primary treatment for fascial fibromatosis between 1946 and 2013. The literature
      indicates that radiotherapy can prevent disease progression and improve symptoms
      for early-stage disease, with low likelihood of significant toxicities.
      CONCLUSION: Early results from our case series are consistent with the
      literature, showing that radiotherapy can provide an effective management option
      for patients with early-stage fascial fibromatosis, and justify consideration of
      radiotherapy as a primary treatment for early-stage disease.

PMID- 24730460
TI  - Effects of storage temperature, storage duration, and subsequent ripening on the
      physicochemical characteristics, volatile compounds, and phytochemicals of
      Western Red nectarine (Prunus persica L. Batsch).
AB  - Western Red nectarines, harvested at commercial maturity, were stored for up to
      20 days at 1, 4, or 8  degrees C and then transferred to 25  degrees C for 0 or 4
      days. The main physicochemical attributes, phytochemicals, and volatile compounds
      were then determined. During storage and ripening, firmness, titratable acidity,
      organic acids, and C6 volatile compounds decreased, whereas ethylene production,
      lactones, and C13 norisoprenoids greatly increased. Soluble solids content,
      sugars, and polyphenols remained quite constant during both stages. During
      storage, vitamin C decreased and carotenoids did not significantly change,
      whereas both greatly increased during ripening. Increased time of low-temperature
      storage has been found to decrease lactones and C13 norisoprenoids in nectarine
      and, consequently, to limit its aroma during maturation. Finally, Western Red
      nectarine was found hardly chilling injury sensitive, and trends for sugars,
      polyphenols and lactones observed in this study were contrary to those generally
      reported in the literature for chilling-injured fruit. 

PMID- 24730461
TI  - High-performance composite membrane with enriched CO2-philic groups and improved
      adhesion at the interface.
AB  - A novel strategy to design a high-performance composite membrane for CO2 capture
      via coating a thin layer of water-swellable polymers (WSPs) onto a porous support
      with enriched CO2-philic groups is demonstrated in this study. First, by
      employing a versatile platform technique combining non-solvent-induced phase
      separation and surface segregation, porous support membranes with abundant CO2
      philic ethylene oxide (EO) groups at the surface are successfully prepared.
      Second, a thin selective layer composed of Pebax MH 1657 is deposited onto the
      support membranes via dip coating. Because of the water-swellable characteristic
      of Pebax and the enriched EO groups at the interface, the composite membranes
      exhibit high CO2 permeance above 1000 GPU with CO2/N2 selectivity above 40 at a
      humidified state (25  degrees C and 3 bar). By tuning the content of the PEO
      segment at the interface, the composite membranes can show either high CO2
      permeance up to 2420 GPU with moderate selectivity of 46.0 or high selectivity up
      to 109.6 with fairly good CO2 permeance of 1275 GPU. Moreover, enrichment of the
      PEO segment at the interface significantly improves interfacial adhesion, as
      revealed by the T-peel test and positron annihilation spectroscopy measurement.
      In this way, the feasibility of designing WSP-based composite membranes by
      enriching CO2-philic groups at the interface is validated. We hope our findings
      may pave a generic way to fabricate high-performance composite membranes for CO2
      capture using cost-effective materials and facile methods. 

PMID- 24730462
TI  - A three-species biofilm model for the evaluation of enamel and dentin
      demineralization.
AB  - Although Streptococcus mutans biofilms have been useful for evaluating the
      cariogenic potential of dietary carbohydrates and the effects of fluoride on
      dental demineralization, a more appropriate biofilm should be developed to
      demonstrate the influence of other oral bacteria on cariogenic biofilms. This
      study describes the development and validation of a three-species biofilm model
      comprising Streptococcus mutans, Actinomyces naeslundii, and Streptococcus
      gordonii for the evaluation of enamel and dentin demineralization after
      cariogenic challenges and fluoride exposure. Single- or three-species biofilms
      were developed on dental substrata for 96 h, and biofilms were exposed to feast
      and famine episodes. The three-species biofilm model produced a large biomass,
      mostly comprising S. mutans (41%) and S. gordonii (44%), and produced significant
      demineralization in the dental substrata, although enamel demineralization was
      decreased by fluoride treatment. The findings indicate that the three-species
      biofilm model may be useful for evaluating the cariogenic potential of dietary
      carbohydrates other than sucrose and determining the effects of fluoride on
      dental substrata.

PMID- 24730463
TI  - Enantio- and diastereoselective synthesis of spiro-epoxyoxindoles.
AB  - An asymmetric synthesis of epoxyoxindoles from isatins has been developed by
      employing chiral sulfur ylides generated in situ from camphor-derived sulfonium
      salts. This reaction allows an efficient access to enantioenriched spiro
      epoxyoxindoles under mild reaction conditions, featuring high yields and
      excellent enantio- and diastereoselectivities. 

PMID- 24730464
TI  - Vitamin D binding protein and vitamin D in human allergen-induced endobronchial
      inflammation.
AB  - Allergic asthma is a chronic disease of the airways associated with airway
      hyperresponsiveness, a variable degree of airflow obstruction, airway remodelling
      and a characteristic airway inflammation. Factors of the vitamin D axis, which
      include vitamin D metabolites and vitamin D binding protein (VDBP), have been
      linked to asthma, but only few data exist about their regulation in the lung
      during acute allergen-induced airway inflammation. Therefore, we analysed the
      regulation of factors of the vitamin D axis during the early- and late-phase
      reaction of allergic asthma. Fifteen patients with mild allergic asthma underwent
      segmental allergen challenge. VDBP was analysed in bronchoalveolar lavage fluid
      (BALF) and serum using the enzyme-linked immunosorbent assay (ELISA) technique.
      25-hydroxyvitamin D(3)[25(OH)D(3)] and 1,25-dihydroxyvitamin
      D(3)[1,25(OH)(2)D(3)] were analysed by a commercial laboratory using the liquid
      chromatography-mass spectrometry (LC/MS) technique. VDBP (median 2.3, range 0.2
      7.1 MUg/ml), 25(OH)D(3) (median 0.060, range < 0.002-3.210 ng/ml) and
      1,25(OH)(2)D(3) (median < 0.1, range < 0.1-2.8 pg/ml) were significantly elevated
      in BALF 24 h but not 10 min after allergen challenge. After correction for plasma
      leakage using the plasma marker protein albumin, VDBP and 25(OH)D(3) were still
      increased significantly while 1,25(OH)(2)D(3) was not. VDBP and 25(OH)D(3) were
      correlated with each other and with the inflammatory response 24 h after allergen
      challenge. Serum concentrations of all three factors were not influenced by
      allergen challenge. In conclusion, we report a significant increase in VDBP and
      25(OH)D(3) in human BALF 24 h after allergen challenge, suggesting a role for
      these factors in the asthmatic late-phase reaction.

PMID- 24730465
TI  - Prospective long-term study of hepatitis B virus reactivation in patients with
      hematologic malignancy.
AB  - BACKGROUND AND AIM: To elucidate the clinical characteristics of hepatitis B
      virus reactivation (HBV-R), we performed a prospective long-term study of
      patients with hematologic malignancy, including both hepatitis B virus (HBV)
      carriers and those with resolved HBV infection. METHODS: Twenty-one patients with
      hematopoietic stem-cell transplants (HSCT) and 36 patients given rituximab-based
      chemotherapy were enrolled. Entecavir was administered prophylactically to eight
      patients with HBV surface antigen (HBsAg). HBV-DNA was measured every month in 49
      patients with resolved HBV infection, and preemptive therapy was given to eight
      patients with HBV-R. RESULTS: HBV-R developed in five (26%) of 19 patients with
      HSCT and three (10%) of 30 patients given rituximab-based chemotherapy. HBV-R
      occurred a median of 3 months (range: 2-10) after the end of rituximab-based
      chemotherapy and 22 months (range: 9-36) after HSCT. HBV-R did not develop in
      patients with an antibodies against HBsAg (anti-HBs) titer exceeding 200 mIU/mL
      at baseline. Mutations in the "a" determinant region with amino acid replacement
      were detected in four of the eight patients with HBV-R. Preemptive therapy
      prevented severe hepatitis related to HBV-R. Entecavir treatment was stopped in
      four patients with HBV-R. Since the withdrawal of entecavir, HBV-DNA has not been
      detected in two patients persistently positive for anti-HBs. No patient had fatal
      hepatitis. CONCLUSIONS: Proper management of patients with HBsAg or resolved HBV
      infection prevented fatal hepatitis related to HBV-R in patients who received
      immunosuppressive or cytotoxic therapy. Entecavir could be safely discontinued in
      patients with HBV-R who had acquired anti-HBs.

PMID- 24730466
TI  - The effect of foveal and parafoveal masks on the eye movements of older and
      younger readers.
AB  - In the present study, we examined foveal and parafoveal processing in older
      compared with younger readers by using gaze-contingent paradigms with 4
      conditions. Older and younger readers read sentences in which the text was either
      a) presented normally, b) the foveal word was masked as soon as it was fixated,
      c) all of the words to the left of the fixated word were masked, or d) all of the
      words to the right of the fixated word were masked. Although older and younger
      readers both found reading when the fixated word was masked quite difficult, the
      foveal mask increased sentence reading time more than 3-fold (3.4) for the older
      readers (in comparison with the control condition in which the sentence was
      presented normally) compared with the younger readers who took 1.3 times longer
      to read sentences in the foveal mask condition (in comparison with the control
      condition). The left and right parafoveal masks did not disrupt reading as
      severely as the foveal mask, though the right mask was more disruptive than the
      left mask. Also, there was some indication that the younger readers found the
      right mask condition relatively more disruptive than the left mask condition.

PMID- 24730467
TI  - Energy-water nexus analysis of enhanced water supply scenarios: a regional
      comparison of Tampa Bay, Florida, and San Diego, California.
AB  - Increased water demand and scarce freshwater resources have forced communities to
      seek nontraditional water sources. These challenges are exacerbated in coastal
      communities, where population growth rates and densities in the United States are
      the highest. To understand the current management dilemma between constrained
      surface and groundwater sources and potential new water sources, Tampa Bay,
      Florida (TB), and San Diego, California (SD), were studied through 2030
      accounting for changes in population, water demand, and electricity grid mix.
      These locations were chosen on the basis of their similar populations, land
      areas, economies, and water consumption characters as well as their coastal
      locations and rising contradictions between water demand and supply. Three
      scenarios were evaluated for each study area: (1) maximization of traditional
      supplies; (2) maximization of seawater desalination; and (3) maximization of
      nonpotable water reclamation. Three types of impacts were assessed: embodied
      energy, greenhouse gas (GHG) emission, and energy cost. SD was found to have
      higher embodied energy and energy cost but lower GHG emission than TB in most of
      its water infrastructure systems because of the differences between the
      electricity grid mixes and water resources of the two regions. Maximizing water
      reclamation was found to be better than increasing either traditional supplies or
      seawater desalination in both regions in terms of the three impact categories.
      The results further imply the importance of assessing the energy-water nexus when
      pursuing demand-side control targets or goals as well to ensure that the
      potentially most economical options are considered. 

PMID- 24730468
TI  - The in-vitro effect of complementary and alternative medicines on cytochrome P450
      2C9 activity.
AB  - OBJECTIVES: The aim of this study is to establish the inhibitory effects of 14
      commonly used complementary and alternative medicines (CAM) on the metabolism of
      cytochrome P450 2C9 (CYP2C9) substrates 7-methoxy-4-trifluoromethyl coumarine
      (MFC) and tolbutamide. CYP2C9 is important for the metabolism of numerous drugs
      and inhibition of this enzyme by CAM could result in elevated plasma levels of
      drugs that are CYP2C9 substrates. Especially for anticancer drugs, which have a
      narrow therapeutic window, small changes in their plasma levels could easily
      result in clinically relevant toxicities. METHODS: The effects of CAM on CYP2C9
      mediated metabolism of MFC were assessed in Supersomes, using the fluorometric
      CYP2C9 inhibition assay. In human liver microsomes (HLM) the inhibition of CYP2C9
      mediated metabolism of tolbutamide was determined, using liquid chromatography
      coupled to tandem mass spectrometry (LC-MS/MS). KEY FINDINGS: The results
      indicated milk thistle as the most potent CYP2C9 inhibitor. For milk thistle,
      silybin (main constituent of milk thistle) was mainly responsible for the
      inhibition of CY2C9. CONCLUSIONS: Milk thistle and green tea were confirmed as
      potent inhibitors of CYP2C9-mediated metabolism of multiple substrates in vitro.
      Clinical studies with milk thistle are recommended to establish the clinical
      relevance of the demonstrated CYP2C9 inhibition.

PMID- 24730470
TI  - Nanopyramid structure for ultrathin c-Si tandem solar cells.
AB  - Recently, ultrathin crystalline silicon solar cells have gained tremendous
      interest because they are deemed to dramatically reduce material usage. However,
      the resulting conversion efficiency is still limited by the incomplete light
      absorption in such ultrathin devices. In this letter, we propose ultrathin a-Si/c
      Si tandem solar cells with an efficient light trapping design, where a
      nanopyramid structure is introduced between the top and bottom cells. The
      superior light harvesting results in a 48% and 35% remarkable improvement of the
      short-circuit current density for the top and bottom cells, respectively.
      Meanwhile, the use of SiOx mixed-phase nanomaterial helps to provide the maximum
      light trapping without paying the price of reduced electrical performance, and
      conversion efficiencies of up to 13.3% have been achieved for the ultrathin
      tandem cell employing only 8 MUm of silicon, which is 29% higher than the result
      obtained for the planar cell. 

PMID- 24730471
TI  - Autophagy in renal ischemia-reperfusion injury: friend or foe?

PMID- 24730472
TI  - Seroprevalence of antibodies to Borrelia burgdorferi sensu lato in healthy adults
      from western Norway: risk factors and methodological aspects.
AB  - The aim of this study was to assess the seroprevalence of antibodies to Borrelia
      burgdorferi sensu lato in a healthy adult population from Sogn and Fjordane
      county in western Norway by different assays. Sera from 1213 blood donors at four
      different blood banks were analysed in Enzygnost Lyme link VlsE/IgG (IgG),
      Enzygnost Borreliosis IgM (IgM), and Immunetics C6 Lyme ELISA kit (C6). Sera
      showing positive or grey-zone reactivities were further examined with Borrelia
      EUROLine-RN-AT IgG blot and Borrelia-EUROLine-RN-AT IgM blot. The seroprevalences
      were 9.6%, 8.2%, 8.4%, 6.4% and 5.7%, respectively. The seroprevalence for IgG
      was lower in the eastern part of the county and in owners of pet animals. It was
      higher in men, and increased with age and number of tick bites. C6 and IgG gave
      comparable results. IgM only was found in 4.5%, more often in women, did not
      increase with age, and showed no relationship with geography, and 56.4% were
      positive in IgM blot. In conclusion, antibodies to B. burgdorferi s.l. are common
      in blood donors in western Norway. The results may be used for evaluation of
      predictive values of test results in patients, as well as a basis for test
      algorithms in the laboratory. 

PMID- 24730473
TI  - Prospective study on the relationship between clinical efficacy of secondary
      hormone therapy with flutamide and neuroendocrine differentiation in patients
      with relapsed prostate cancer after first line hormone therapy.
AB  - OBJECTIVE: The aim of this study was to prospectively verify the relationship
      between the clinical efficacies of secondary hormone therapy for castration
      resistant prostate cancer (CRPC) following first line hormone therapy and
      neuroendocrine differentiation (NED). MATERIAL AND METHODS: Forty-six consecutive
      patients with CRPC following first line hormone therapy who were treated with
      flutamide as secondary hormone therapy were prospectively assessed with a median
      follow-up of 21 months. Serum chromogranin A (CgA), as a marker of NED, was
      measured using an immunoradiometric assay. RESULTS: Of the 46 patients, 22 (48%)
      responded to the secondary hormone therapy as a 50% or more reduction from
      baseline prostate-specific antigen (PSA) with a median response duration of 9.2
      months. The PSA response group was correlated with significantly favorable cancer
      specific survival (CSS) (92% vs 59% at 5 years, p = 0.0146) compared with the non
      response group. Above-normal CgA levels at study entry were detected in 15
      patients (33%), but no association with CSS was identified. Data on CgA kinetics
      were available in 35 patients. The CgA levels before and at 3 months during the
      treatment were similar. However, eight patients (23%) with an increase in CgA
      level of a quarter or more from baseline had a tendency for worse CSS (63% vs 84%
      at 5 years, p = 0.0507) compared with the remaining patients. CONCLUSION: Within
      limitations, in this study secondary hormone therapy with flutamide was effective
      for CRPC following first line hormone therapy. The above-normal CgA level in the
      first hormone resistance phase is mostly unrelated to prognosis. However, some
      patients with a remarkable increase in CgA in a short duration may have an
      unfavorable prognosis caused by NED as well.

PMID- 24730474
TI  - Angiosarcoma of the prostate: a more frequent finding in the future owing to
      radiotherapy? A literature review with treatment implications based on a case
      report.
AB  - OBJECTIVE: An increase in the incidence of prostate angiosarcoma may be expected
      owing to the exponential increase in the use of radiotherapy for prostate
      carcinoma in recent decades and the possible aetiology of radiation exposure on
      the development of angiosarcoma in general. The objective of this study was to
      give an overview of cases in the literature based on a case report of prostate
      angiosarcoma in a hospital in the Netherlands, and to discuss optimal treatment.
      MATERIAL AND METHODS: All (related) articles In PubMed/Medline and Embase with
      possible cases of angiosarcoma were screened on title and abstract. A case of
      prostate angiosarcoma identified in the authors' institution was included.
      RESULTS: The literature search yielded 13 cases of prostate angiosarcoma. The
      earliest six publications lack essential data. Four patients had a history of
      radiotherapy. The present patient developed angiosarcoma following brachytherapy
      for prostate cancer. Therapy consisted of radical surgery with or without
      chemotherapy in five cases. In eight cases curative therapy was not reported or
      not possible. Mean follow-up was only 1 year. Four patients died within 1 year of
      diagnosis, irrespective of treatment choice. One patient, treated with a
      combination of radical surgery and adjuvant chemotherapy, was still alive 36
      months after therapy. CONCLUSIONS: The findings confirm that prostate
      angiosarcoma is mostly radiation induced. This patient is the first case of
      prostate angiosarcoma after primary brachytherapy. Angiosarcoma may occur more
      often in the future owing to widespread use of brachytherapy and radiotherapy of
      the prostate. Current guidelines on management of angiosarcoma suggest radical
      surgery in local disease as the primary treatment of choice.

PMID- 24730475
TI  - Racial/ethnic disparities in alcohol-related problems: differences by gender and
      level of heavy drinking.
AB  - BACKGROUND: While prior studies have reported racial/ethnic disparities in
      alcohol-related problems at a given level of heavy drinking (HD), particularly
      lower levels, it is unclear whether these occur in both genders and are an
      artifact of racial/ethnic differences in drink alcohol content. Such information
      is important to understanding disparities and developing specific, targeted
      interventions. This study addresses these questions and examines disparities in
      specific types of alcohol problems across racial-gender groups. METHODS: Using
      2005 and 2010 National Alcohol Survey data (N = 7,249 current drinkers), gender
      stratified regression analyses were conducted to assess black-white and Hispanic
      white disparities in alcohol dependence and negative drinking consequences at
      equivalent levels of HD. HD was measured using a gender-specific, composite
      drinking-patterns variable derived through factor analysis. Analyses were
      replicated using adjusted-alcohol consumption variables that account for group
      differences in drink alcohol content based on race/ethnicity, gender, age, and
      alcoholic beverage. RESULTS: Compared with white men, black and Hispanic men had
      higher rates of injuries/accidents/health and social consequences, and marginally
      greater work/legal consequences (p < 0.10). Hispanic women had marginally higher
      rates of social consequences. In main effects models controlling for
      demographics, light drinking and HD, only black women and men had greater odds of
      alcohol-related problems relative to whites. Interaction models indicated that
      compared with whites, black women had greater odds of dependence at all levels of
      HD, while both black and Hispanic men had elevated risk of alcohol problems only
      at lower levels of HD. Drink alcohol content adjustments did not significantly
      alter findings for either gender. CONCLUSIONS: This study highlights the gender
      specific nature of racial/ethnic disparities. Interventions focused on reducing
      HD might not address disparities in alcohol-related problems that exist at low
      levels of HD. Future research should consider the potential role of environmental
      and genetic factors in these disparities.

PMID- 24730476
TI  - Detection of microRNA in tumor cells using exonuclease III and graphene oxide
      regulated signal amplification.
AB  - In this study, we developed a label-free, ultrasensitive graphene oxide (GO)
      based probe for the detection of oligonucleotides by laser desorption/ionization
      mass spectrometry (LDI-MS). On the basis of simple pi-pi stacking and
      electrostatic interactions between rhodamine 6G (R6G) and GO, we prepared the
      nanocomposite R6G-modified GO (R6G-GO). Signal intensities of R6G increased in
      mass spectra in the presence of single-stranded oligonucleotides under pulsed
      laser irradiation (355 nm) of R6G-GO. In addition, the signal intensity of R6G
      was stronger in the presence of short oligonucleotides. Because small
      oligonucleotides improve the LDI efficiency of R6G on GO, we designed an enzyme
      amplified signal transduction probe system for the detection of microRNA (miRNA).
      After specific digestion of the probe DNA (pDNA) strand from pDNA/miRNA
      hybridized complexes by exonuclease III (Exo III), the resulting small
      oligonucleotide fragments increased the R6G signal during LDI-MS of R6G-GO. In
      addition, the signal intensity of the R6G ions increased with increasing
      concentrations of the target miRNA. Coupling this enzyme reaction and R6G-GO with
      LDI-MS enabled the detection of miRNA at concentrations of the femtomolar (fM)
      level. We also demonstrated the analysis of miRNA in tumor cells and utilized
      this R6G-GO probe in the detection of a single-nucleotide polymorphism (SNP) in
      the Arg249Ser unit of the TP53 gene. This simple, rapid, and sensitive detection
      system based on the coupling of functional GO with LDI-MS appears to have great
      potential as a tool for the bioanalyses of oligonucleotides and proteins. 

PMID- 24730477
TI  - Use of wild genotypes in breeding program increases strawberry fruit sensorial
      and nutritional quality.
AB  - This study evaluated 20 advanced selections, derived from a strawberry
      interspecific backcross program, and their parents for fruit weight, commercial
      yield, acidity, sugar content, antioxidant capacity, and phenol and anthocyanin
      contents. Phytochemical profiling analysis was performed to determine the
      compositional characteristics of the improved selections in comparison with their
      parents and an important commercial variety ('Elsanta'). Advanced selections
      showed substantial improvement for agronomic and nutritional quality parameters.
      From the profiling analysis there was evidence for specific improvements in fruit
      phytochemical contents; new advanced selections had substantially increased fruit
      flavonol, anthocyanin, and ellagitannin contents compared to their parent
      cultivar 'Romina' and, for flavonols and ellagitannins, compared to a standard
      cultivar 'Elsanta'. Such results confirm that an appropriate breeding program
      that includes wild strawberry germplasm can produce new strawberry cultivars with
      a well-defined improvement in fruit nutritional and nutraceutical values. 

PMID- 24730478
TI  - Questioning the moral enhancement project.

PMID- 24730479
TI  - Is there an ethical obligation to disclose controversial risk? A question from
      the ACCORD Trial.
AB  - Researchers designing a clinical trial may be aware of disputed evidence of
      serious risks from previous studies. These researchers must decide whether and
      how to describe these risks in their model informed consent document. They have
      an ethical obligation to provide fully informed consent, but does this obligation
      include notice of controversial evidence? With ACCORD as an example, we describe
      a framework and criteria that make clear the conditions requiring inclusion of
      important controversial risks. The ACCORD model consent document did not include
      notice of prior trials with excess death. We develop and explain a new standard
      labeled risk in equipoise. We argue that our approach provides an optimal level
      of integrity to protect the informational needs of the reasonable volunteers who
      agree to participate in clinical trials. We suggest language to be used in a
      model consent document and the informed consent discussion when such
      controversial evidence exists. 

PMID- 24730480
TI  - Challenging the requirements for disclosing risk to clinical research
      participants.

PMID- 24730481
TI  - Disclosing controversial risk in informed consent: how serious is serious?

PMID- 24730482
TI  - Disclosure of risks and uncertainties are especially vital in light of
      regenerative medicine.

PMID- 24730483
TI  - Equipoise and nonmedical risks.

PMID- 24730484
TI  - The ethical imperative of risk disclosure in research: the answer is always yes.

PMID- 24730485
TI  - Egalitarianism and moral bioenhancement.
AB  - A number of philosophers working in applied ethics and bioethics are now
      earnestly debating the ethics of what they term "moral bioenhancement." I argue
      that the society-wide program of biological manipulations required to achieve the
      purported goals of moral bioenhancement would necessarily implicate the state in
      a controversial moral perfectionism. Moreover, the prospect of being able to
      reliably identify some people as, by biological constitution, significantly and
      consistently more moral than others would seem to pose a profound challenge to
      egalitarian social and political ideals. Even if moral bioenhancement should
      ultimately prove to be impossible, there is a chance that a bogus science of
      bioenhancement would lead to arbitrary inequalities in access to political power
      or facilitate the unjust rule of authoritarians; in the meantime, the debate
      about the ethics of moral bioenhancement risks reinvigorating dangerous ideas
      about the extent of natural inequality in the possession of the moral faculties. 

PMID- 24730486
TI  - Would moral bioenhancement lead to an inegalitarian society?

PMID- 24730487
TI  - Why moral bioenhancement is a bad idea and why egalitarianism would make it
      worse.

PMID- 24730488
TI  - Moral capacity enhancement does not entail moral worth enhancement.

PMID- 24730489
TI  - Egalitarianism and successful moral bioenhancement.

PMID- 24730490
TI  - Voluntary moral bioenhancement is a solution to Sparrow's concerns.

PMID- 24730491
TI  - Against fetishism about egalitarianism and in defense of cautious moral
      bioenhancement.

PMID- 24730492
TI  - The possible effects of moral bioenhancement on political privileges and fair
      equality of opportunity.

PMID- 24730493
TI  - A public ethos of enhancement across Asia.

PMID- 24730494
TI  - Moral enhancement--"hard" and "soft" forms.

PMID- 24730496
TI  - The ethics of disclosing to research subjects the availability of off-label
      marketed drugs.

PMID- 24730497
TI  - Researchers have an ethical obligation to disclose the availability of off-label
      marketed drugs.

PMID- 24730498
TI  - The relevance of research study phase to disclosure of off-label drug
      availability.

PMID- 24730499
TI  - Which alternatives should investigators disclose to research subjects?

PMID- 24730500
TI  - Ethics of continuing to provide a drug on an open-label extension study for an
      "unapproved indication".

PMID- 24730501
TI  - When should open-label extension studies be stopped?

PMID- 24730502
TI  - The role of clinical equipoise and practical considerations in deciding whether
      to continue to provide a drug on an open-label extension study for an "unapproved
      indication".

PMID- 24730503
TI  - Open-label extension studies: are they really research?

PMID- 24730505
TI  - Response to the open peer commentaries on "Is there an ethical obligation to
      disclose controversial risk? A question from the ACCORD Trial".

PMID- 24730506
TI  - Response to open peer commentaries on "The ethics of advertising for health care
      services".

PMID- 24730507
TI  - Prediction of daily ratings of psychosocial functioning: can ratings of
      personality disorder traits and functioning be distinguished?
AB  - Current categorical and dimensional conceptualizations of personality disorder
      (PD) typically confound pathological PD traits with distress and impairment
      (dysfunction). The current study examines whether dimensions of personality
      pathology and psychosocial dysfunction can be psychometrically distinguished. To
      that end, we collected self-report ratings of personality pathology and
      dysfunction at baseline, along with daily ratings of dysfunctional behavior, over
      10 consecutive days. Correlations revealed substantial overlap between traits and
      dysfunction measured at baseline. However, follow-up hierarchical regressions
      revealed that baseline dysfunction ratings incrementally predicted daily
      dysfunction ratings after accounting for personality trait ratings, suggesting
      that traits and dysfunction are at least partially differentiable. However, the
      incremental effects were stronger for some dysfunction domains (i.e., Self
      Mastery and Basic Functioning) than for others (Well-Being and Interpersonal),
      suggesting that maladaptive trait measures are more confounded with the latter
      types of impairment. These findings suggest that distinguishing maladaptive PD
      traits from functioning in PD classification systems is likely more difficult
      than would be expected, a finding that has important implications for the
      competing Section II and Section III conceptualizations of PD presented in the
      Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition.

PMID- 24730509
TI  - Arixanthomycins A-C: Phylogeny-guided discovery of biologically active eDNA
      derived pentangular polyphenols.
AB  - Soil microbiomes are a rich source of uncharacterized natural product
      biosynthetic gene clusters. Here we use short conserved biosynthetic gene
      sequences (natural product sequence tags) amplified from soil microbiomes as
      phylogenetic markers to correlate genotype to chemotype and target the discovery
      of novel bioactive pentangular polyphenols from the environment. The heterologous
      expression of an environmental DNA-derived gene cluster (the ARX cluster), whose
      ketosynthase beta (KSbeta) sequence tag was phylogenetically distinct from any
      known KSbeta sequence, led to the discovery of the arixanthomycins.
      Arixanthomycin A (1) exhibits potent antiproliferative activity against human
      cancer cell lines.

PMID- 24730510
TI  - Amphiphilic triblock copolymers with PEGylated hydrocarbon structures as
      environmentally friendly marine antifouling and fouling-release coatings.
AB  - The ideal marine antifouling (AF)/fouling-release (FR) coating should be non
      toxic, while effectively either resisting the attachment of marine organisms (AF)
      or significantly reducing their strength of attachment (FR). Many recent studies
      have shown that amphiphilic polymeric materials provide a promising solution to
      producing such coatings due to their surface dual functionality. In this work,
      poly(ethylene glycol) (PEG) of different molecular weights (Mw = 350, 550) was
      coupled to a saturated difunctional alkyl alcohol to generate amphiphilic
      surfactants (PEG-hydrocarbon-OH). The resulting macromolecules were then used as
      side chains to covalently modify a pre-synthesized PS8 K-b-P(E/B)25 K-b-PI10 K
      (SEBI or K3) triblock copolymer, and the final polymers were applied to glass
      substrata through an established multilayer surface coating technique to prepare
      fouling resistant coatings. The coated surfaces were characterized with AFM, XPS
      and NEXAFS, and evaluated in laboratory assays with two important fouling algae,
      Ulva linza (a green macroalga) and Navicula incerta, a biofilm-forming diatom.
      The results suggest that these polymer-coated surfaces undergo surface
      reconstruction upon changing the contact medium (polymer/air vs polymer/water),
      due to the preferential interfacial aggregation of the PEG segment on the surface
      in water. The amphiphilic polymer-coated surfaces showed promising results as
      both AF and FR coatings. The sample with longer PEG chain lengths (Mw = 550 g
      mol(-1)) exhibited excellent properties against both algae, highlighting the
      importance of the chemical structures on ultimate biological performance. Besides
      reporting synthesis and characterization of this new type of amphiphilic surface
      material, this work also provides insight into the nature of PEG/hydrocarbon
      amphiphilic coatings, and this understanding may help in the design of future
      generations of fluorine-free, environmentally friendly AF/FR polymeric coatings.

PMID- 24730511
TI  - Distinguishing immunorelated haemocytopenia from idiopathic cytopenia of
      undetermined significance (ICUS): a bone marrow abnormality mediated by
      autoantibodies.
AB  - In recent years we have observed that some patients with idiopathic cytopenia of
      undetermined significance (ICUS) responded well to corticosteroid and high-dose
      intravenous immunoglobulin treatment, indicating that some cytopenia in ICUS
      might be mediated by autoantibodies. In this study, we analysed 166 ICUS cases
      retrospectively, some of which were autoantibodies detected on haemopoietic cells
      in bone marrow (BM) by BM mononuclear cell (BMMNC)-Coombs test, flow cytometry
      (FCM), Western blot and immunofluorescence (IF). We found that 25.9% (43 of 166)
      of the cases had autoantibodies positive verified with BMMNC-Coombs test or FCM
      analysis, 72.1% (31 of 43) of whom had immunoglobulin (Ig)G autoantibody positive
      by Western blot. IgG could be detected in the erythroblastic islands on the BM
      smear of nine (32.1%, nine of 28) ICUS patients with autoantibodies by IF. Of
      these 43 patients, the median percentage of reticulocytes was 1.79%. More than
      half the patients had hyper-BM cellularity with a higher percentage of nucleated
      erythroid cells in the sternum. Total response rates to immunosuppressive therapy
      at 6, 12, 24 and > 36 months were 46.5% (20 of 43), 75% (30 of 40), 77.4% (24 of
      31) and 66.7% (16 of 24), respectively. We termed this group of ICUS cases with
      autoantibodies as immunorelated haemocytopenia (or BMMNC-Coombs test-positive
      haemocytopenia). 

PMID- 24730512
TI  - Characterization of two tartary buckwheat R2R3-MYB transcription factors and
      their regulation of proanthocyanidin biosynthesis.
AB  - Tartary buckwheat (Fagopyrum tataricum Gaertn.) contains high concentrations of
      flavonoids. The flavonoids are mainly represented by rutin, anthocyanins and
      proanthocyanins in tartary buckwheat. R2R3-type MYB transcription factors (TFs)
      play key roles in the transcriptional regulation of the flavonoid biosynthetic
      pathway. In this study, two TF genes, FtMYB1 and FtMYB2, were isolated from F.
      tataricum and characterized. The results of bioinformatic analysis indicated that
      the putative FtMYB1 and FtMYB2 proteins belonged to the R2R3-MYB family and
      displayed a high degree of similarity with TaMYB14 and AtMYB123/TT2. In vitro and
      in vivo evidence both showed the two proteins were located in the nucleus and
      exhibited transcriptional activation activities. During florescence, both FtMYB1
      and FtMYB2 were more highly expressed in the flowers than any other organ. The
      overexpression of FtMYB1 and FtMYB2 significantly enhanced the accumulation of
      proanthocyanidins (PAs) and showed a strong effect on the target genes'
      expression in Nicotiana tabacum. The expression of dihydroflavonol-4-reductase
      (DFR) was upregulated to 5.6-fold higher than that of control, and the expression
      level was lower for flavonol synthase (FLS). To our knowledge, this is the first
      functional characterization of two MYB TFs from F. tataricum that control the PA
      pathway. 

PMID- 24730514
TI  - Template-assisted low temperature synthesis of functionalized graphene for
      ultrahigh volumetric performance supercapacitors.
AB  - We demonstrated the fabrication of functionalized graphene nanosheets via low
      temperature (300  degrees C) treatment of graphite oxide with a slow heating rate
      using Mg(OH)2 nanosheets as template. Because of its dented sheet with high
      surface area, a certain amount of oxygen-containing groups, and low pore volume,
      the as-obtained graphene delivers both ultrahigh specific gravimetric and
      volumetric capacitances of 456 F g(-1) and 470 F cm(-3), almost 3.7 times and 3.3
      times higher than hydrazine reduced graphene, respectively. Especially, the
      obtained volumetric capacitance is the highest value so far reported for carbon
      materials in aqueous electrolytes. More importantly, the assembled supercapacitor
      exhibits an ultrahigh volumetric energy density of 27.2 Wh L(-1), which is among
      the highest values for carbon materials in aqueous electrolytes, as well as
      excellent cycling stability with 134% of its initial capacitance after 10,000
      cycles. Therefore, the present work holds a great promise for future design and
      large-scale production of high performance graphene electrodes for portable
      energy storage devices.

PMID- 24730513
TI  - Biomarker-based calibration of retrospective exposure predictions of
      perfluorooctanoic acid.
AB  - Estimated historical exposures and serum concentrations of perfluorooctanoic acid
      (PFOA) have been extensively used in epidemiologic studies that examined
      associations between PFOA exposures and adverse health outcomes among residents
      in highly exposed areas in the Mid-Ohio Valley. Using measured serum PFOA levels
      in 2005-2006, we applied two calibration methods to these retrospective exposure
      predictions: (1) multiplicative calibration and (2) Bayesian pharmacokinetic
      calibration with larger adjustments to more recent exposure estimates and smaller
      adjustments to exposure estimates for years farther in the past. We conducted
      simulation studies of various hypothetical exposure scenarios and compared
      hypothetical true historical intake rates with estimates based on mis-specified
      baseline exposure and pharmacokinetic models to find the method with the least
      bias. The Bayesian method outperformed the multiplicative method if a change to
      bottled water consumption was not reported or if the half-life of PFOA was mis
      specified. On the other hand, the multiplicative method outperformed the Bayesian
      method if actual tap water consumption rates were systematically overestimated.
      If tap water consumption rates gradually decreased over time because of
      substitution with bottled water or other liquids, neither method clearly
      outperformed another. Calibration of retrospective exposure estimates using
      recently collected biomarkers may help reduce uncertainties in environmental
      epidemiologic studies. 

PMID- 24730515
TI  - Single-crystalline LiFePO4 nanosheets for high-rate Li-ion batteries.
AB  - The lithiation/delithiation in LiFePO4 is highly anisotropic with lithium-ion
      diffusion being mainly confined to channels along the b-axis. Controlling the
      orientation of LiFePO4 crystals therefore plays an important role for efficient
      mass transport within this material. We report here the preparation of single
      crystalline LiFePO4 nanosheets with a large percentage of highly oriented {010}
      facets, which provide the highest pore density for lithium-ion
      insertion/extraction. The LiFePO4 nanosheets show a high specific capacity at low
      charge/discharge rates and retain significant capacities at high C-rates, which
      may benefit the development of lithium batteries with both favorable energy and
      power density. 

PMID- 24730516
TI  - Initial phase performance in a 30-s verbal fluency task as being reflective of
      aging effect.
AB  - AIM: The purpose of the present study was to investigate if performance in a 30-s
      verbal semantic fluency task (i.e. animal naming) across five elderly aged groups
      (60-64; 65-69; 70-74; 75-79; 80-84 years) would be reflective of aging effect.
      METHODS: We analyzed differences in performance across 5-s phases and the moment
      of first word production in these five age groups. RESULTS: The following results
      were obtained: (i) with increasing age, the total number of words produced
      gradually declined (P < 0.001); (ii) there were significant differences in
      performance among the age groups in three phases (0-5, 6-10, 16-20 s) (P < 0.05);
      and (iii) the first word production within the first 5-s phase was significantly
      delayed in the 75-79 years and 80-84 years age groups compared with the rest of
      the age groups. CONCLUSIONS: Performance in the initial 5-s phase might be
      sensitive to cognitive degeneration in normal older adults.

PMID- 24730518
TI  - Characteristics of gastric cancer according to Helicobacter pylori infection
      status.
AB  - BACKGROUND AND AIMS: The definition and incidence of gastric cancer (GC) without
      Helicobacter pylori (Hp) infection varies between studies. The aim of our study
      was to compare the characteristics of GC according to Hp infection status.
      METHODS: We evaluated the presence of Hp infection in 1833 GC patients with rapid
      urease tests, serology examinations, and histological evaluations. GC was
      classified as GC with current Hp infection (HpC-GC), GC with past Hp infection
      (HpP-GC), and GC not associated with Hp infection (HpN-GC). HpP-GC was defined as
      GC without current infection but with a positive serology test, glandular
      atrophy, and/or intestinal metaplasia. HpN-GC was defined as GC with negative Hp
      test results and no histological changes. RESULTS: The numbers of HpC-GC, HpP-GC,
      and HpN-GC were 1378 (75.2%), 412 (22.5%), and 43 (2.3%), respectively. Among GCs
      without current infection, 90.5% (412/455) were associated with HpP-GC. HpP-GCs
      were more common in older and male patients, had an increased incidence of
      synchronous cancer, and less frequently had a diffuse-type histology than HpC
      GCs. HpN-GCs were more common in younger, female patients; had a higher
      proportion of diffuse-type cancers; and more frequently showed distant metastasis
      than HpP-GCs. In the 40s, the proportion of HpP-GCs with diffuse-type histology
      (41.9%) was lower than that of HpC-GCs (60.3%) (P = 0.016). The difference was
      also significant in the 50s (29.1% vs 40.1%, respectively, P = 0.004).
      CONCLUSIONS: Most GCs in Korea without current Hp infection showed evidence of
      past Hp infection. The proportion of GCs with diffuse-type histology decreased in
      patients with past infection.

PMID- 24730519
TI  - Retraction of: Cooperation between subunits is essential for high-affinity
      binding of N-acetyl-D-hexosamines to dimeric soluble and dimeric cellular forms
      of human CD69.

PMID- 24730520
TI  - Inhibition of autophagy strengthens celastrol-induced apoptosis in human
      pancreatic cancer in vitro and in vivo models.
AB  - OBJECTIVES: Celastrol, a quinone methide triterpenoid, could induce apoptosis in
      pancreatic cancer cells. The purpose of this study is to determine whether there
      is protective autophagy after celastrol treatment in pancreatic cancer cells and
      the synergistic effects of celastrol and 3-MA in vitro and in vivo. METHODS: The
      cells viability was measured using MTT assays. Degree of apoptosis and amount of
      autophagic vacuoles were measured by flow cytometry. Immunofluorescence was
      adapted to monitor the localization of autophagic protein LC3-II. Expression of
      LC3-II, cleaved caspase-3, Bax and bcl-2 was detected by immunoblot.
      Autophagosomes were observed by electron microscopy. The synergistic effect of
      celastrol and 3- MA in vivo was studied in the MiaPaCa-2 xenograft tumor model.
      RESULTS: Celastrol increased the level of autophagy in pancreatic cancer cells.
      Furthermore in vitro, when inhibiting the autophagy with 3-MA, the level of
      celastrol-induced apoptosis elevated; after upgrading autophagy by starvation,
      the level of celastrol-induced apoptosis descended. 3-MA enhanced celastrol
      induced apoptosis and inhibitory effect on tumor growth in vivo. CONCLUSIONS: In
      pancreatic cancer, celastrol treatment increased the level of autophagy to
      protect cancer cells against apoptosis. Autophagy inhibitor 3-MA could improve
      the therapeutic effect of celastrol in vitro and in vivo.

PMID- 24730521
TI  - A possible role for interleukin 37 in the pathogenesis of Behcet's disease.
AB  - Interleukin 37 has been found to play a significant regulatory role in the innate
      immune response. It is not yet known whether IL-37 has also been involved in the
      development of Behcet's disease (BD), a chronic systemic inflammatory disease. To
      examine the role of IL-37 in the pathogenesis of BD, a number of experiments were
      performed. IL-37 expression in peripheral blood mononuclear cells (PBMCs) from BD
      patients and normal controls was measured by RT-PCR and flow cytometry. Monocyte
      derived Dendritic Cells (DCs) were cultured with or without IL-37 and levels of
      cytokines in the culture supernatants were measured by ELISA. The DC surface
      markers, reactive oxygen species (ROS) production and mitogen-activated protein
      kinase (MAPK) activation were measured by flow cytometry. The effect of IL-37
      treated DCs on the development of CD4(+) T cells was measured by ELISA and flow
      cytometry. The results show that both IL-37 mRNA level and protein expression
      were significantly decreased in PBMCs from active BD patients compared to normal
      controls. DCs stimulated with rIL-37 showed a decreased expression of IL-6, IL
      1beta and TNF-alpha, and a higher production of IL-27. rIL-37 significantly
      inhibited the production of ROS by DCs and reduced the activation of ERK1/2, JNK
      and P38 MAPK in DCs. rIL-37-treated DCs remarkably inhibited Th17 and Th1 cell
      responses as compared to control DCs. rIL-37 did not affect the expression of DC
      surface markers (CD40, CD86, CD80 and HLA-DR) or IL-10 production by DCs. We
      conclude that a decreased IL-37 expression in active BD patients may trigger the
      production of pro-inflammatory cytokines and ROS in association with activation
      of Th1 and Th17 cells by DCs. 

PMID- 24730522
TI  - Role of Wnt signaling in tissue fibrosis, lessons from skeletal muscle and
      kidney.
AB  - Several studies have provided clear evidence of the importance of Wnt signaling
      in the function of several tissues. Wnt signaling has been related to several
      cellular processes including pre-natal development, cell division, regeneration
      and stem cell generation. By contrast, deregulation of this pathway has been
      associated with several diseases such as cancer, Alzheimer's disease, diabetes
      and, in recent years, fibrotic diseases in tissues such as skeletal muscle and
      kidney. Fibrotic diseases are characterized by an increase in the production and
      accumulation of extracellular matrix (ECM) components leading to the loss of
      tissue architecture and function. In a classical view, several molecules are
      related to the establishment of the fibrotic condition, including angiotensin II,
      transforming growth factorbeta(TGF-beta) and the connective tissue growth factor
      (CTGF) and a crosstalk has been suggested between these signaling molecules and
      the Wnt pathway. Skeletal muscle fibrosis, the most common disease, is typical of
      muscle dystrophies, where deregulation of the regenerative process in postnatal
      muscle leads to fibrotic differentiation and eventually to the failure of
      skeletal muscle. The fibrotic condition is also present in kidney pathologies
      such as polycystic kidney disease (PKD), in which fibrosis leads to a loss of
      tubule architecture and to a loss of function, which in almost all cases requires
      kidney surgery. A new actor in the pro-fibrotic effect of Wnt signaling in the
      kidney has been described, the primary cilium, an organelle that plays an
      important role in the onset of fibrosis. The aim of this review is to discuss the
      pro-fibrotic effect of Wnt signaling in both skeletal muscle and kidney, and to
      try to understand how this pathway is associated with the TGF-beta, CTGF and
      angiotensin II pro-fibrotic pathway. 

PMID- 24730523
TI  - G-protein coupled receptor 124 (GPR124) in endothelial cells regulates vascular
      endothelial growth factor (VEGF)-induced tumor angiogenesis.
AB  - G protein-coupled receptor 124 (GPR124; also called tumor endothelial marker 5,
      TEM5) is highly expressed in tumor vasculature. While recent studies have
      revealed a role in vasculogenesis, evidence for GPR124 function in tumor
      angiogenesis is lacking. Here, we demonstrate that GPR124 is required for VEGF
      induced tumor angiogenesis. GPR124 silencing in human endothelial cells inhibited
      mouse xenograft tumor angiogenic vessel formation and tumor growth. GPR124
      regulated VEGF-induced tumor angiogenic processes in vitro including cell-cell
      interaction, permeability, migration, invasion, and tube formation. Therefore,
      GPR124 plays a key role in VEGF-induced tumor angiogenesis.

PMID- 24730524
TI  - Detection of circulating tumor cells from lung cancer patients in the era of
      targeted therapy: promises, drawbacks and pitfalls.
AB  - Interest in biomarkers in the field of thoracic oncology is focused on the search
      for new robust tests for diagnosis (in particular for screening), prognosis and
      theragnosis. These biomarkers can be detected in tissues and/or cells, but also
      in biological fluids, mainly the blood. In this context, there is growing
      interest in the detection of circulating tumor cells (CTCs) in the blood of lung
      cancer patients since CTC identification, enumeration and characterization may
      have a direct impact on diagnosis, prognosis and theragnosis in the daily
      clinical practice. Many direct and indirect methods have been developed to detect
      and characterize CTCs in lung cancer patients. However, these different
      approaches still hold limitations and many of them have demonstrated unequal
      sensitivity and specificity. Indeed, these methods hold advantages but also
      certain disadvantages. Therefore, despite the promises, it is currently difficult
      and premature to apply this methodology to the routine care of lung cancer
      patients. This situation is the consequence of the analysis of the methodological
      approaches for the detection and characterization of CTCs and of the results
      published to date. Finally, the advent of targeted cancer therapies in thoracic
      oncology has stimulated considerable interest in non-invasive detection of
      genomic alterations in tumors over time through the analysis of CTCs, an approach
      that may help clinicians to optimize therapeutic strategies for lung cancer
      patients. We describe here the main methods for CTC detection, the advantages and
      limitations of these different approaches and the potential usefulness and value
      of CTC characterization in the field of thoracic oncology. 

PMID- 24730525
TI  - Fgf10: a paracrine-signaling molecule in development, disease, and regenerative
      medicine.
AB  - The Fgf family comprises 22 members with diverse functions in development,
      repair, metabolism, and neuronal activities. Fgf10 mediates biological responses
      by activating Fgf receptor 2b (Fgfr2b) with heparin/heparan sulfate in a
      paracrine manner. Fgf10 and Fgfr2b are expressed in mesenchymal and epithelial
      tissues, respectively. Fgf10 is an epithelial-mesenchymal signaling molecule.
      Fgf10 knockout mice show severe phenotypes with complete truncation of the fore-
      and hindlimbs and die shortly after birth due to impaired lung development,
      indicating that Fgf10 serves as an essential regulator of lung and limb
      formation. Fgf10 also has roles in the development of white adipose tissue,
      heart, liver, brain, kidney, cecum, ocular glands, thymus, inner ear, tongue,
      trachea, eye, stomach, prostate, salivary gland, mammary gland, and whiskers. The
      diverse phenotypes of Fgf10 knockout mice are closely related to those of Fgfr2
      knockout mice, suggesting that Fgf10 acts as a major ligand for Fgfr2b in mouse
      multi-organ development. Aplasia of lacrimal and salivary glands and lacrimo
      auriculo-dento-digital syndrome are caused by Fgf10 mutations in humans. Variants
      in Fgf10 may be involved in an increased risk for limb deficiencies and cleft lip
      and palate. Patients with Fgf10 haploinsufficiency have lung function parameters
      indicating chronic obstructive pulmonary disease. Fgf10 induces migration and
      invasion in pancreatic cancer cells. Fgf10 signaling may be involved in an
      increased risk for breast cancer. Fgf10 also induces the differentiation of
      embryonic stem cells into a gut-like structure, cardiomyocytes, and hepatocytes.
      These findings indicate the crucial roles of Fgf10 in development, disease, and
      regenerative medicine. 

PMID- 24730526
TI  - TP73, an under-appreciated player in non-Hodgkin lymphoma pathogenesis and
      management.
AB  - The TP73 gene is a member of the TP53 family with high structural homology to p53
      and capable of transactivating p53 target genes. The TP73 gene locus which is
      highly conserved and complex, encodes for two classes of isoforms TAp73 (tumor
      suppressor isoforms containing the transactivation domain) and DeltaNp73
      (oncogenic isoforms, truncated and lacking the transactivation domain) with
      opposing effects. The balance between TAp73 and DeltaNp73 isoforms and their
      harmony with other members of the TP73 family regulate various cellular responses
      such as apoptosis, autophagy, proliferation, and differentiation. The
      transcriptionally active isoforms of p73 are capable of inducing apoptosis in
      cancer cells independent of p53 status. Unlike p53, p73 is rarely mutated in
      cancers, however, the ratio of DeltaNp73:TAp73 is frequently up-regulated in many
      carcinomas and is indicative of poor prognosis. Moreover, p73 is an important
      determinant of chemosensitivity and radiosensitivity, the two major treatment
      modalities for lymphoma. In the current review, we will provide an overview of
      recent progress discussing the role of TP73 in cancer, specifically addressing
      its relevance to lymphomagenesis, progression, therapy resistance, and its
      potential as a novel therapeutic target. 

PMID- 24730527
TI  - Toll-like receptors in human multiple myeloma: new insight into inflammation
      related pathogenesis.
AB  - Multiple myeloma (MM) is a clonal neoplasm characterized by expansion of
      malignant plasma cells in the bone marrow causing various complications including
      osteolytic lesions and impaired immune function. It has recently been reported
      that human myeloma cells express multiple Toll-like receptors (TLRs), and their
      activation-induced functional responses show heterogeneity among cell lines and
      patient samples. TLRs are critical germ-line encoded molecules expressed in
      immune cells as well as in a variety of cancer cells. In multiple myeloma, they
      may induce cell growth and proliferation or promote cell death. In fact, our
      current knowledge of Toll-like receptor function has gone beyond their main
      function as triggers of innate and adaptive immune responses. Considering the
      essential role of bone marrow microenvironment components in myeloma tumor
      expansion, survival, invasion and drug resistance, TLR triggering may contribute
      to adhesion-induced or de novo drug resistance of MM cells. Future preclinical
      and clinical studies are needed to address if TLRs can be exploited as novel
      therapeutic targets for MM. 

PMID- 24730528
TI  - A surveillance tool using mobile phone short message service to reduce alcohol
      consumption among alcohol-dependent patients.
AB  - BACKGROUND: In public health settings, short message service (SMS) appears to be
      a promising low-cost modality for reducing alcohol consumption. Here, we test a
      simple interactive SMS-based helpline with detoxified alcohol-dependent patients
      to extend findings to curative settings. METHODS: This controlled, prospective, 2
      group before-after block-assignment, open pilot study tested the feasibility and
      efficacy of an 8-week outpatient interactive mobile phone SMS intervention (n =
      42) against treatment as usual (TAU; n = 38) after inpatient detoxification.
      Patients were asked whether they needed any help via an automatically generated
      text message twice a week. A therapist called the individual back when notified.
      Alcohol consumption was assessed using the telephone version of Form-90 4 and 8
      weeks after discharge from inpatient detoxification. The primary end point was
      defined as attaining low-risk consumption (males <=30 g or 3.75 units per
      drinking day (DDD); females <=20 g or 2.5 units per DDD) 8 weeks after discharge.
      Missing data were replaced by multiple imputation. RESULTS: Among all messages
      sent, 20.5% were followed by a phone call. Feasibility and acceptability were
      good, as indicated by successful implementation of the SMS procedure and the
      rapid inclusion of patients. Adherence was satisfactory with 57.14% of the
      participants replying to at least 50% of the prompts. Patients reported a typical
      preadmission DDD of 281.25 +/- 244.61 g. In the SMS group, 55.7% of 42 patients,
      and 40% of 38 patients in the TAU group, achieved low-risk consumption (risk
      diff: 0.16; 95% CI -0.06 to 0.37; p = 0.122). CONCLUSIONS: In detoxified alcohol
      dependent patients, relapse prevention based on SMS was well received and
      implemented efficiently and rapidly. An adequately powered multicenter study is
      currently being conducted to test the nonsignificant but encouraging findings of
      this exploratory study with more rigorous trial methods (ISRCTN78350716).

PMID- 24730529
TI  - Response letter to "autophagy in renal ischemia-reperfusion injury: friend or
      foe?".

PMID- 24730531
TI  - Pleiotropic effects of platelet P2Y12 receptor inhibitors: fact or fiction?
AB  - P2Y12 inhibitors constitute an essential part of the antithrombotic treatment,
      with proven clinical benefit in acute coronary syndromes and after percutaneous
      coronary interventions. Substantial evidence has emerged that, apart from their
      primary antiplatelet action, P2Y12 receptor inhibitors exhibit several off-target
      effects. In this review, we present the supporting evidence of P2Y12 inhibitors'
      pleiotropic actions, discuss their clinical implications and underscore the
      necessity for further research on this issue. 

PMID- 24730530
TI  - Exploration of type II binding mode: A privileged approach for kinase inhibitor
      focused drug discovery?
AB  - The ATP site of kinases displays remarkable conformational flexibility when
      accommodating chemically diverse small molecule inhibitors. The so-called
      activation segment, whose conformation controls catalytic activity and access to
      the substrate binding pocket, can undergo a large conformational change with the
      active state assuming a 'DFG-in' and an inactive state assuming a 'DFG-out'
      conformation. Compounds that preferentially bind to the DFG-out conformation are
      typically called 'type II' inhibitors in contrast to 'type I' inhibitors that
      bind to the DFG-in conformation. This review surveys the large number of type II
      inhibitors that have been developed and provides an analysis of their
      crystallographically determined binding modes. Using a small library of type II
      inhibitors, we demonstrate that more than 200 kinases can be targeted, suggesting
      that type II inhibitors may not be intrinsically more selective than type I
      inhibitors.

PMID- 24730532
TI  - Granulomas obstruct lymphatics in all layers of the intestine in Crohn's disease.
AB  - After an earlier study defining immunolabeled lymphoid follicles, obstructed
      lymphatics, and granulomas of the diseased ilea of 24 Crohn's disease patients,
      we chose to trace the lymphatics of these cases and 10 additional by serial
      sectioning. Particular attention was given to establishing physical continuity
      between granuloma-obstructed lymphatics and lymphatics with 'lymphocytic
      thrombi'. Formalin-fixed paraffin-embedded tissue blocks from resected diseased
      ilea and proximal colons from 34 patients were reviewed. Patients were 13 men and
      21 women, aged 14-60 years. Duration of disease ranged from 1 month to 10 years.
      Immunohistochemistry employed D2-40 antibody to label lymphatics and anti-CD68 to
      label granulomas. Twenty-nine of the 34 (85%) resection tissues had
      lymphangectasia, in mucosa, submucosa, and subserosa. In 53% of the specimens,
      lymphatics of the various layers were obstructed by granulomas that filled the
      lumina. In 44%, 15/34, there were also distended lymphatics that were totally
      plugged with lymphocytes. In 10 of the 15, serial sections revealed continuity
      between the lymphocyte-plugged lymphatics and the endolymphatic granulomatous
      obstruction downstream. In 5 of the cases, D2-40 immunostaining revealed
      redundant lymphatic endothelium interwoven with the granuloma cells. Granulomas
      totally obstruct lymphatics in all layers of the intestine in Crohn's disease.
      Upstream of these obstructions, lymphatics are distended with lymphocytes. The
      degree and extent of this potentially irreversible 'lymphangitis nodosa' have
      undoubtedly confounded treatment regimens and clinical trials. There currently
      are no imaging methods to demonstrate the lymphangitis, nor treatments to resolve
      it. 

PMID- 24730533
TI  - Neonatal maternal separation up-regulates protein signalling for cell survival in
      rat hypothalamus.
AB  - We have previously reported that in response to early life stress, such as
      maternal hyperthyroidism and maternal separation (MS), the rat hypothalamic
      vasopressinergic system becomes up-regulated, showing enlarged nuclear volume and
      cell number, with stress hyperresponsivity and high anxiety during adulthood. The
      detailed signaling pathways involving cell death/survival, modified by adverse
      experiences in this developmental window remains unknown. Here, we report the
      effects of MS on cellular density and time-dependent fluctuations of the
      expression of pro- and anti-apoptotic factors during the development of the
      hypothalamus. Neonatal male rats were exposed to 3 h-daily MS from postnatal days
      2 to 15 (PND 2-15). Cellular density was assessed in the hypothalamus at PND 21
      using methylene blue staining, and neuronal nuclear specific protein and glial
      fibrillary acidic protein immunostaining at PND 36. Expression of factors related
      to apoptosis and cell survival in the hypothalamus was examined at PND 1, 3, 6,
      9, 12, 15, 20 and 43 by Western blot. Rats subjected to MS exhibited greater cell
      density and increased neuronal density in all hypothalamic regions assessed. The
      time course of protein expression in the postnatal brain showed: (1) decreased
      expression of active caspase 3; (2) increased Bcl-2/Bax ratio; (3) increased
      activation of ERK1/2, Akt and inactivation of Bad; PND 15 and PND 20 were the
      most prominent time-points. These data indicate that MS can induce hypothalamic
      structural reorganization by promoting survival, suppressing cell death pathways,
      increasing cellular density which may alter the contribution of these modified
      regions to homeostasis.

PMID- 24730534
TI  - Coupling of the radiosensitivity of melanocyte stem cells to their dormancy
      during the hair cycle.
AB  - Current studies have revealed that stem cells are more radiosensitive than mature
      cells. As somatic stem cells are mostly kept in a quiescent state, this conflicts
      with Bergonie and Tribondeau's law that actively mitotic cells are the most
      radiosensitive. In this study, we focused on hair graying to understand the
      stress-resistance of melanocyte stem cells (McSCs). We used Dct-H2B-GFP
      transgenic mice which enables the stable visualization of McSCs and an anti-Kit
      monoclonal antibody which selectively eradicates amplifying McSCs. The results
      demonstrate that quiescent McSCs are rather radiosensitive, but the coexistence
      of non-quiescent McSCs provides the stem cell pool with radioresistance. The
      irradiated quiescent McSCs prematurely differentiate in the niche upon their
      activation without sufficiently renewing themselves for cyclic hair pigmentation.
      These data indicate that tissue radiosensitivity is largely dependent on the
      state of somatic stem cells under their local microenvironment.

PMID- 24730535
TI  - Advancing the extended parallel process model through the inclusion of response
      cost measures.
AB  - This study advances the Extended Parallel Process Model through the inclusion of
      response cost measures, which are drawbacks associated with a proposed response
      to a health threat. A sample of 502 college students completed a questionnaire on
      perceptions regarding sexually transmitted infections and condom use after
      reading information from the Centers for Disease Control and Prevention on the
      health risks of sexually transmitted infections and the utility of latex condoms
      in preventing sexually transmitted infection transmission. The questionnaire
      included standard Extended Parallel Process Model assessments of perceived threat
      and efficacy, as well as questions pertaining to response costs associated with
      condom use. Results from hierarchical ordinary least squares regression
      demonstrated how the addition of response cost measures improved the predictive
      power of the Extended Parallel Process Model, supporting the inclusion of this
      variable in the model. 

PMID- 24730536
TI  - Prognostic significance of [18F]fluorodeoxyglucose-positron emission tomography
      in peripheral T-cell lymphoma treated with stem cell transplantation: a
      retrospective analysis.

PMID- 24730537
TI  - Programmed haploidentical hematopoietic stem cell infusion combined with systemic
      chemotherapy improves the outcomes of patients with refractory or relapsed
      lymphoma.

PMID- 24730538
TI  - Phase 1 study of radiosensitization using bortezomib in patients with relapsed
      non-Hodgkin lymphoma receiving radioimmunotherapy with 131I-tositumomab.
AB  - Radioimmunotherapy (RIT) is effective treatment for indolent non-Hodgkin
      lymphomas (NHLs), but response durations are usually limited, especially in
      aggressive NHL. We hypothesized that administration of bortezomib as a
      radiosensitizer with RIT would be tolerable and improve efficacy in NHL. This
      phase 1 dose-escalation study evaluated escalating doses of bortezomib combined
      with 131I-tositumomab in patients with relapsed/refractory NHL. Twenty-five
      patients were treated. Treatment was well tolerated, with primarily hematologic
      toxicity. The maximum tolerated dose (MTD) was determined to be 0.9 mg/m2
      bortezomib, in combination with a standard dose of 75 cGy 131I-tositumomab.
      Sixteen patients responded (64%), including 44% complete responses (CRs), with
      82% CR in patients with follicular lymphoma (FL). At a median follow-up of 7
      months, median progression-free survival was 7 months, and seven of 11 patients
      with FL remained in remission at a median of 22 months. In conclusion, bortezomib
      can be safely administered in combination with 131I-tositumomab with promising
      response rates.

PMID- 24730539
TI  - Retrospective analysis of Philadelphia chromosome-positive acute lymphoblastic
      leukemia treated with allogeneic hematopoietic stem cell transplant versus
      chemotherapy combined with tyrosine kinase inhibitor.

PMID- 24730541
TI  - Mediastinal isolated myeloid sarcoma: a single-institution experience.

PMID- 24730540
TI  - Autoimmune diseases during treatment with immunomodulatory drugs in multiple
      myeloma: selective occurrence after lenalidomide.
AB  - Immunomodulatory drugs (IMiDs) may favor autoimmune disease (AD) occurrence. We
      conducted a retrospective study to evaluate AD occurrence among IMiD-treated
      patients with myeloma. Patients were grouped into three classes depending on the
      type of IMiD engaged. The first group included patients treated with thalidomide
      (Thal) (n = 474), the second group with lenalidomide (Len) (n = 140) and patients
      in the third group were first treated with Thal followed by Len (Thal-Len) (n =
      94). Absolute risk of AD was 0.4% for patients treated with Thal, 4.3% for Len
      and 1.1% for Thal-Len. ADs manifested prevalently as autoimmune cytopenias (55%),
      although we observed one vasculitis, one optic neuritis, one Graves' disease and
      one polymyositis. ADs occurred preferentially in the first months of IMiD
      treatment. A previous autologous transplant was shown to be a significant risk
      factor. All ADs were managed with IMiD discontinuation and steroids, resolving in
      a few weeks, except for Graves' disease and polymyositis.

PMID- 24730542
TI  - Challenges of pain masking in the management of soft tissue disorders: optimizing
      patient outcomes with a multi-targeted approach.
AB  - Current approaches to managing soft tissue injuries often rely upon the use of
      non-steroidal anti-inflammatory drugs (NSAIDs). The use of NSAIDs in this manner
      is contentious, and some believe that the risks of using NSAIDs can outweigh any
      potential benefit. In this article the issues of toxicity, pain masking and
      return to full activity are reviewed, and an alternative strategy for the
      management of inflammation in soft tissue injuries is proposed. We consider that
      a multi-targeted approach has the potential to improve healing, reduce additional
      injury from premature return to full activity as a consequence of pain masking,
      and improve prognosis for many patients with soft tissue injuries.

PMID- 24730543
TI  - Enhanced consumer goal achievement through strengths-based group supervision.
AB  - PURPOSE: This article seeks to enhance and support consumer-centered care in
      psychiatric rehabilitation through the use of strengths-based group supervision
      (SBGS). SOURCES USED: The article is based on social science research findings,
      30 years of experience with the model, and the literature on supervision.
      Relevant findings from research on the model are included. CONCLUSIONS AND
      IMPLICATIONS FOR PRACTICE: SBGS is a promising approach for improving consumer
      goal achievement and centeredness. It warrants further implementation and
      research.

PMID- 24730544
TI  - Ultralow thermal conductivity of multilayers with highly dissimilar Debye
      temperatures.
AB  - Thermal transport in multilayers (MLs) has attracted significant interest and
      shows promising applications. Unlike their single-component counterparts, MLs
      exhibit a thermal conductivity that can be effectively engineered by both the
      number density of the layers and the interfacial thermal resistance between
      layers, with the latter being highly tunable via the contrast of acoustic
      properties of each layer. In this work, we experimentally demonstrated an
      ultralow thermal conductivity of 0.33 +/- 0.04 W m(-1) K(-1) at room temperature
      in MLs made of Au and Si with a high interfacial density of ~0.2 interface nm(
      1). The measured thermal conductivity is significantly lower than the amorphous
      limit of either Si or Au and is also much lower than previously measured MLs with
      a similar interfacial density. With a Debye temperature ratio of ~3.9 for Au and
      Si, the Au/Si MLs represent the highest mismatched system in inorganic MLs
      measured to date. In addition, we explore the prior theoretical prediction that
      full phonon dispersion could better model the interfacial thermal resistance
      involving materials with low Debye temperatures. Our results demonstrate that MLs
      with highly dissimilar Debye temperatures represent a rational approach to
      achieve ultralow thermal conductivity in inorganic materials and can also serve
      as a platform for investigating interfacial thermal transport. 

PMID- 24730545
TI  - Physical performance and quality of life in single and recurrent fallers: data
      from the Improving Medication Prescribing to Reduce Risk of Falls study.
AB  - AIM: Although guidelines regarding falls prevention make a clear distinction
      between single and recurrent fallers, differences in functional status, physical
      performance, and quality of life in single and recurrent fallers have not been
      thoroughly investigated. Therefore, we investigated the differences in functional
      status, physical performance and health-related quality of life (HRQoL) between
      single and recurrent fallers. METHODS: From October 2008 to October 2011, 616
      community-dwelling older adults who visited the emergency department as a result
      of a fall were enrolled. Physical performance was assessed with the Timed Up & Go
      (TUG) test, the Five Times Sit to Stand (FTSS) test, handgrip strength and the
      tandem stand test. Functional status was measured using the activities of daily
      living and instrumental activities of daily living scales. HRQoL was measured
      using the European Quality of Life five dimensions (EQ-5D), and the Short Form-12
      version 2. A general linear model was used to compare the means of the scores.
      RESULTS: Recurrent falls in community-dwelling older adults were associated with
      poorer physical performance as measured by the TUG test (P < 0.001), FTSS test (P
      = 0.011), handgrip strength (P < 0.001) and tandem stand (P < 0.001), and lower
      HRQoL scores as measured by the EQ-5D (P = 0.006) and SF-12 (P = 0.006 and P =
      0.012). CONCLUSION: The present findings provide further evidence that recurrent
      fallers have poorer physical performance and quality of life than single fallers.
      Recurrent falls might be a symptom of underlying disease and frailty, and reason
      for further assessment.

PMID- 24730546
TI  - A numerical investigation of flow around octopus-like arms: near-wake vortex
      patterns and force development.
AB  - The fluid dynamics of cephalopods has so far received little attention in the
      literature, due to their complexity in structure and locomotion. The flow around
      octopuses, in particular, can be complicated due to their agile and dexterous
      arms, which frequently display some of the most diverse mechanisms of motion. The
      study of this flow amounts to a specific instance of the hydrodynamics problem
      for rough tapered cylinder geometries. The outstanding manipulative and locomotor
      skills of octopuses could inspire the development of advanced robotic arms, able
      to operate in fluid environments. Our primary aim was to study the hydrodynamic
      characteristics of such bio-inspired robotic models and to derive the
      hydrodynamic force coefficients as a concise description of the vortical flow
      effects. Utilizing computational fluid dynamic methods, the coefficients were
      computed on realistic morphologies of octopus-like arm models undergoing
      prescribed solid-body movements; such motions occur in nature for short durations
      in time, e.g. during reaching movements and exploratory behaviors. Numerical
      simulations were performed on translating, impulsively rotating, and maneuvering
      arms, around which the flow field structures were investigated. The results
      reveal in detail the generation of complex vortical flow structures around the
      moving arms. Hydrodynamic forces acting on a translating arm depend on the angle
      of incidence; forces generated during impulsive rotations of the arms are
      independent of their exact morphology and the angle of rotation; periodic motions
      based on a slow recovery and a fast power stroke are able to produce considerable
      propulsive thrust while harmonic motions are not. Parts of these results have
      been employed in bio-inspired models of underwater robotic mechanisms. This
      investigation may further assist elucidating the hydrodynamics underlying aspects
      of octopus locomotion and exploratory behaviors. 

PMID- 24730547
TI  - In memory of Theodore Millon.

PMID- 24730548
TI  - Theodore Millon.

PMID- 24730549
TI  - Serum cytokine/chemokine profiles in acute exacerbation of chronic hepatitis B:
      clinical and mechanistic implications.
AB  - BACKGROUND AND AIMS: Acute exacerbation (AE) of chronic hepatitis B virus (HBV)
      infection is common and negatively impacts the clinical outcome. Although upsurge
      of viral load always precedes or coincides with AE, the underlying immunological
      mechanisms remain unclear and were investigated. METHODS: We prospectively
      followed the serum cytokine/chemokine profiles, viral load, and alanine
      aminotransferase (ALT) levels in 250 patients and identified 44 consecutive
      patients (male: 72.7%; age: 40.4 +/- 9.7 years; hepatitis B e antigen [HBeAg]
      positivity: 63.6%; genotype B/C: 75%/25%) who developed AE during the follow-up
      in a medical center. The impact of clinical characteristics (age, gender, HBeAg,
      ALT, HBV genotype), cytokines (tumor necrosis factor-alpha, interferon gamma,
      interleukin [IL]-2, IL-4, IL-6, and IL-10), and chemokines (CXCL10/interferon
      gamma-induced protein [IP]-10, CCL2/MCP-1, CXCL9/MIG, CCL5/RANTES, and CXCL8/IL
      8) on the serum HBV DNA dynamics at different time points (baseline, peak of
      serum HBV DNA level, peak of serum ALT level, and after AE) were analyzed.
      RESULTS: Of 44 patients, serum HBV DNA level surged before the peak of serum ALT
      level in 23 (52.3%), and coincided with the peak of ALT in 21 (47.7%). The
      upsurge of serum viral load significantly correlated with the increase of IL-10
      (P = 0.0037) and CXCL10/IP-10 (P = 0.0044). Upsurge of serum viral load was
      preceded by an increase in serum IL-4 (P < 0.05), IL-6 (P < 0.05), and IL-10 (P <
      0.05). Combination of HBV genotype, IL-6 level at baseline, and ALT level at the
      peak of serum HBV DNA reliably predicted subsequent AE pattern (P = 0.0116).
      CONCLUSIONS: Enhanced Th2 activity is likely involved in the surge of HBV DNA
      level before hepatitis exacerbation.

PMID- 24730550
TI  - Long-term experiment with orchard floor management systems: influence on apple
      yield and chemical composition.
AB  - The study focuses on the response of apple primary and secondary metabolism and
      some important quality parameters to three living mulch treatments, classical
      herbicide fallow, and black polypropylene strip application in two apple
      cultivars. Primary and secondary metabolites were analyzed after 10 years of
      ground cover experiments. Soluble solids, firmness, and color measurements
      indicate differences among orchard floor management treatments. Significantly,
      lower levels of individual sugars have been measured in fruit of different living
      mulch treatments compared with fruit harvested from trees subjected to the
      herbicide strip treatment. Total sugar content was higher in fruit of the
      herbicide strip treatment in both cultivars analyzed. Significantly higher levels
      of total organic acids were only detected in 'Pinova' fruit of the Festuca ovina
      L. treatment. Long-term response of both cultivars to living mulch treatments
      indicated that apples increase the accumulation of almost all analyzed individual
      phenolic compounds. 

PMID- 24730551
TI  - Evidence from FTIR difference spectroscopy that D1-Asp61 influences the water
      reactions of the oxygen-evolving Mn4CaO5 cluster of photosystem II.
AB  - Understanding the mechanism of photosynthetic water oxidation requires
      characterizing the reactions of the water molecules that serve as substrate or
      that otherwise interact with the oxygen-evolving Mn4CaO5 cluster. FTIR difference
      spectroscopy is a powerful tool for studying the structural changes of hydrogen
      bonded water molecules. For example, the O-H stretching mode of water molecules
      having relatively weak hydrogen bonds can be monitored near 3600 cm(-1), the D-O
      D bending mode can be monitored near 1210 cm(-1), and highly polarizable networks
      of hydrogen bonds can be monitored as broad features between 3000 and 2000 cm(
      1). The two former regions are practically devoid of overlapping vibrational
      modes from the protein. In Photosystem II, water oxidation requires a precisely
      choreographed sequence of proton and electron transfer steps in which proton
      release is required to prevent the redox potential of the Mn4CaO5 cluster from
      rising to levels that would prevent its subsequent oxidation. Proton release
      takes place via one or more proton egress pathways leading from the Mn4CaO5
      cluster to the thylakoid lumen. There is growing evidence that D1-D61 is the
      initial residue of one dominant proton egress pathway. This residue interacts
      directly with water molecules in the first and second coordination spheres of the
      Mn4CaO5 cluster. In this study, we explore the influence of D1-D61 on the water
      reactions accompanying oxygen production by characterizing the FTIR properties of
      the D1-D61A mutant of the cyanobacterium, Synechocystis sp. PCC 6803. On the
      basis of mutation-induced changes to the carbonyl stretching region near 1747 cm(
      1), we conclude that D1-D61 participates in the same extensive networks of
      hydrogen bonds that have been identified previously by FTIR studies. On the basis
      of mutation-induced changes to the weakly hydrogen-bonded O-H stretching region,
      we conclude that D1-D61 interacts with water molecules that are located near the
      Cl(-)(1) ion and that deprotonate or participate in stronger hydrogen bonds as a
      result of the S1 to S2 and S2 to S3 transitions. On the basis of the elimination
      of a broad feature between 3100 and 2600 cm(-1), we conclude that the highly
      polarizable network of hydrogen bonds whose polarizability or protonation state
      increases during the S1 to S2 transition involves D1-D61. On the basis of the
      elimination of features in the D-O-D bending region, we conclude that D1-D61
      forms a hydrogen bond to one of the H2O molecules whose H-O-H bending mode
      changes in response to the S1 to S2 transition. The elimination of this H2O
      molecule in the D1-D61A mutant provides one rationale for the decreased
      efficiency of water oxidation in this mutant. Finally, we discuss reasons why the
      recent conclusion that a substrate-containing cluster of five water molecules
      accepts a proton from the Mn4CaO5 cluster during the S1 to S2 transition and
      deprotonates during subsequent S state transitions should be reassessed. 

PMID- 24730552
TI  - Influence of variation potential on resistance of the photosynthetic machinery to
      heating in pea.
AB  - Electrical signals [action potentials (APs) and variation potentials (VPs)]
      induced by local stimuli are a mechanism that underlies rapid plant response to
      environmental factors. Such signals induce a number of functional responses,
      including changes in photosynthesis. Ultimately, these responses are considered
      to increase plant resistance to stress factors, but this question has been poorly
      investigated. We studied the influence of VP on photosynthesis and resistance of
      the photosynthetic machinery to heating in leaves of pea (Pisum sativum).
      Localized burning induced a VP that decreased photosynthesis parameters [CO(2)
      assimilation rate and quantum yields of photosystem I (PSI) and photosystem II
      (PSII)]. The photosynthetic response was initiated by a decrease in
      photosynthesis dark-stage activity, which in turn increased resistance of PSI to
      heating. Three results supported this hypothesized mechanism: (1) the magnitude
      of VP-induced decrease in CO(2) assimilation and enhanced PSI resistance to
      heating were highly correlated; (2) the VP influence on PSI resistance to heating
      was suppressed under a low external CO(2) concentration and (3) decreasing
      external CO(2) concentration imitated the VP-induced photosynthetic response and
      increased PSI resistance to heating.

PMID- 24730556
TI  - Enhanced removal of uranium(VI) by nanoscale zerovalent iron supported on Na
      bentonite and an investigation of mechanism.
AB  - The reductive removal of U(VI) by nanoscale zerovalent iron (NZVI) was enhanced
      by using Na(+)-saturated bentonite (Na-bent) as the support, and the mechanism
      for the enhanced removal were investigated comprehensively. Under the same
      experimental conditions, NZVI supported on the negatively charged Na-bent showed
      much higher removal efficiency (99.2%) of cationic U(VI) than either bare NZVI
      (48.3%) or NZVI supported on the positively charged bentonite (Al-bent) did.
      Subsequent experimental investigations revealed the unique roles of bentonite on
      enhancing the reactivity and reusability of NZVI. First, Na-bent can buffer the
      pH in reaction media, besides preventing NZVI from aggregation. Second, Na-bent
      promoted the mass transfer of U(VI) from solution to NZVI surface, leading to the
      enhanced removal efficiency. Third, the bentonite may transfer some insoluble
      reduction products away from the iron surface according to X-ray absorption fine
      structure (XAFS) study. Finally, Na-bent as the adsorbent to Fe(II) makes it more
      reactive with U(VI), which enhanced stoichiometrically the reduction capacity of
      NZVI besides accelerating the reaction rate. 

PMID- 24730557
TI  - Neuropilin-1-targeted gold nanoparticles enhance therapeutic efficacy of
      platinum(IV) drug for prostate cancer treatment.
AB  - Platinum-based anticancer drugs such as cisplatin, oxaliplatin, and carboplatin
      are some of the most potent chemotherapeutic agents but have limited applications
      due to severe dose-limiting side effects and a tendency for cancer cells to
      rapidly develop resistance. The therapeutic index can be improved through use of
      nanocarrier systems to target cancer cells efficiently. We developed a unique
      strategy to deliver a platinum(IV) drug to prostate cancer cells by constructing
      glutathione-stabilized (Au@GSH) gold nanoparticles. Glutathione (GSH) has well
      known antioxidant properties, which lead to cancer regression. Here, we exploit
      the advantages of both the antioxidant properties and high surface-area-to-volume
      ratio of Au@GSH NPs to demonstrate their potential for delivery of a platinum(IV)
      drug by targeting the neuropilin-1 receptor (Nrp-1). A lethal dose of a
      platinum(IV) drug functionalized with the Nrp-1-targeting peptide (CRGDK) was
      delivered specifically to prostate cancer cells in vitro. Targeted peptide
      ensures specific binding to the Nrp-1 receptor, leading to enhanced cellular
      uptake level and cell toxicity. The nanocarriers were themselves nontoxic, but
      exhibited high cytotoxicity and increased efficacy when functionalized with the
      targeting peptide and drug. The uptake of drug-loaded nanocarriers is dependent
      on the interaction with Nrp-1 in cell lines expressing high (PC-3) and low (DU
      145) levels of Nrp-1, as confirmed through inductively coupled plasma mass
      spectrometry and confocal microscopy. The nanocarriers have effective anticancer
      activity, through upregulation of nuclear factor kappa-B (NF-kappaB) protein (p50
      and p65) expression and activation of NF-kappaB-DNA-binding activity. Our
      preliminary investigations with platinum(IV)-functionalized gold nanoparticles
      along with a targeting peptide hold significant promise for future cancer
      treatment. 

PMID- 24730558
TI  - The changing of the guard: past, present, and future directions for the journal
      of personality assessment.

PMID- 24730560
TI  - Modeled exposure assessment via inhalation and dermal pathways to airborne
      semivolatile organic compounds (SVOCs) in residences.
AB  - Exposure to airborne semivolatile organic compounds (SVOCs) in indoor and outdoor
      environments of humans may lead to adverse health risks. Thus, we established a
      model to evaluate exposure to airborne SVOCs. In this model, SVOCs phase-specific
      concentrations were estimated by a kinetic partition model accounting for
      particle dynamics. The exposure pathways to airborne SVOCs included inhalation
      exposure to gas- and particle-phases, dermal exposure by direct gas-to-skin
      pathway and dermal exposure by direct particle deposition. Exposures of defined
      "reference people" to two typical classifications of SVOCs, one generated from
      both indoor and outdoor sources, represented by polycyclic aromatic hydrocarbons
      (PAHs), and the other generated mainly from only indoor sources, represented by
      di 2-ethylhexyl phthalate (DEHP), were analyzed as an example application of the
      model. For PAHs with higher volatility, inhalation exposure to gas-phase, ranging
      from 6.03 to 16.4 ng/kg/d, accounted for the most of the exposure to the airborne
      phases. For PAHs with lower volatility, inhalation exposure to particle-phase,
      ranging from 1.48 to 1.53 ng/kg/d, was the most important exposure pathway. As
      for DEHP, dermal exposure via direct gas-to-skin pathway was 460 ng/kg/d, which
      was the most striking exposure pathway when the barrier effect of clothing was
      neglected. 

PMID- 24730559
TI  - Ambient particulate matter induces an exacerbation of airway inflammation in
      experimental asthma: role of interleukin-33.
AB  - High levels of ambient environmental particulate matter (PM10 i.e. < 10 MUm
      median aerodynamic diameter) have been linked to acute exacerbations of asthma.
      We examined the effects of delivering a single dose of Sydney PM10 by intranasal
      instillation to BALB/c mice that had been sensitized to ovalbumin and challenged
      repeatedly with a low (~3 mg/m(3)) mass concentration of aerosolized ovalbumin
      for 4 weeks. Responses were compared to animals administered carbon black as a
      negative control, or a moderate (~30 mg/m(3)) concentration of ovalbumin to
      simulate an allergen-induced acute exacerbation of airway inflammation. Delivery
      of PM10 to mice, in which experimental mild chronic asthma had previously been
      established, elicited characteristic features of enhanced allergic inflammation
      of the airways, including eosinophil and neutrophil recruitment, similar to that
      in the allergen-induced exacerbation. In parallel, there was increased expression
      of mRNA for interleukin (IL)-33 in airway tissues and an increased concentration
      of IL-33 in bronchoalveolar lavage fluid. Administration of a monoclonal
      neutralizing anti-mouse IL-33 antibody prior to delivery of particulates
      significantly suppressed the inflammatory response induced by Sydney PM10, as
      well as the levels of associated proinflammatory cytokines in lavage fluid. We
      conclude that IL-33 plays a key role in driving airway inflammation in this novel
      experimental model of an acute exacerbation of chronic allergic asthma induced by
      exposure to PM10.

PMID- 24730562
TI  - Ubiquitin profiling in liver using a transgenic mouse with biotinylated
      ubiquitin.
AB  - Ubiquitination is behind most cellular processes, with ubiquitin substrates being
      regulated variously according to the number of covalently conjugated ubiquitin
      molecules and type of chain formed. Here we report the first mammalian system for
      ubiquitin proteomics allowing direct validation of the MS-identified proteins. We
      created a transgenic mouse expressing biotinylated ubiquitin and demonstrate its
      use for the isolation of ubiquitinated proteins from liver and other tissues. The
      specificity and strength of the biotin-avidin interaction allow very stringent
      washes, so only proteins conjugated to ubiquitin are isolated. In contrast with
      recently available antibody-based approaches, our strategy allows direct
      validation by immunoblotting, therefore revealing the type of ubiquitin chains
      (mono or poly) formed in vivo. We also identify the conjugating E2 enzymes that
      are ubiquitin-loaded in the mouse tissue. Furthermore, our strategy allows the
      identification of candidate cysteine-ubiquitinated proteins, providing a strategy
      to identify those on a proteomic scale. The novel in vivo system described here
      allows broad access to tissue-specific ubiquitomes and can be combined with
      established mouse disease models to investigate ubiquitin-dependent therapeutical
      approaches. 

PMID- 24730561
TI  - Methylation and gene expression responses to ethanol feeding and betaine
      supplementation in the cystathionine beta synthase-deficient mouse.
AB  - BACKGROUND: Alcoholic steatohepatitis (ASH) is caused in part by the effects of
      ethanol (EtOH) on hepatic methionine metabolism. METHODS: To investigate the
      phenotypic and epigenetic consequences of altered methionine metabolism in this
      disease, we studied the effects of 4-week intragastric EtOH feeding with and
      without the methyl donor betaine in cystathionine beta synthase (CbetaS)
      heterozygous C57BL/6J mice. RESULTS: The histopathology of early ASH was induced
      by EtOH feeding and prevented by betaine supplementation, while EtOH feeding
      reduced and betaine supplementation maintained the hepatic methylation ratio of
      the universal methyl donor S-adenosylmethionine (SAM) to the methyltransferase
      inhibitor S-adenosylhomocysteine (SAH). MethylC-seq genomic sequencing of
      heterozygous liver samples from each diet group found 2 to 4% reduced methylation
      in gene bodies, but not promoter regions of all autosomes of EtOH-fed mice, each
      of which were normalized in samples from mice fed the betaine-supplemented diet.
      The transcript levels of nitric oxide synthase (Nos2) and DNA methyltransferase 1
      (Dnmt1) were increased, while those of peroxisome proliferator receptor-alpha
      (Pparalpha) were reduced in EtOH-fed mice, and each was normalized in mice fed
      the betaine-supplemented diet. DNA pyrosequencing of CbetaS heterozygous samples
      found reduced methylation in a gene body of Nos2 by EtOH feeding that was
      restored by betaine supplementation and was correlated inversely with its
      expression and positively with SAM/SAH ratios. CONCLUSIONS: The present study has
      demonstrated relationships among EtOH induction of ASH with aberrant methionine
      metabolism that was associated with gene body DNA hypomethylation in all
      autosomes and was prevented by betaine supplementation. The data imply that EtOH
      induced changes in selected gene transcript levels and hypomethylation in gene
      bodies during the induction of ASH are a result of altered methionine metabolism
      that can be reversed through dietary supplementation of methyl donors.

PMID- 24730563
TI  - Kidney transplant recipients treated with belatacept exhibit increased naive and
      transitional B cells.
AB  - Phase III clinical studies have shown that kidney transplant (KT) recipients
      treated with the costimulation blocker belatacept exhibited a better renal
      allograft function and lower donor-specific anti-HLA immunization when compared
      to recipients treated with calcineurin inhibitors (CNI). We analyzed B cell
      phenotype in KT recipients treated with belatacept and stable renal function (N =
      13). Results were compared to those observed in stable patients treated with CNI
      (N = 12), or with chronic antibody-mediated rejection (N = 5). Both
      transcriptional profile and phenotypic characterization of peripheral B cells
      were performed by real-time polymerase chain reaction and flow cytometry,
      respectively. In belatacept group, the frequency and absolute number of
      transitional B cells as defined by both phenotypes: CD19(+) CD24(hi) CD38(hi) and
      CD19(+) IgD(hi) CD38(hi) CD27(-) , as well as naive B cells were significantly
      higher compared with CNI group. B cell activating factor (BAFF) and BAFF receptor
      mRNA levels were significantly lower in belatacept group than in CNI group. These
      results show for the first time that belatacept influences B cell compartment by
      favoring the occurrence of transitional B cells with potential regulatory
      properties, as described in operational tolerant patients. This role may explain
      the lower alloimmunization rate observed in belatacept-treated patients.

PMID- 24730564
TI  - Perceived peer drinking norms and responsible drinking in UK university settings.
AB  - BACKGROUND: Heavy drinking is common among students at UK universities. US
      students overestimate how much their peers drink and correcting this through the
      use of social norm messages may promote responsible drinking. OBJECTIVES: We
      tested whether there is an association between perceived campus drinking norms
      and usual drinking behavior in UK university students and whether norm messages
      about responsible drinking correct normative misperceptions and increase
      students' intentions to drink responsibly. METHOD: 1,020 UK university students
      took part in an online study. Participants were exposed to one of five message
      types: a descriptive norm, an injunctive norm, a descriptive and injunctive norm,
      or one of two control messages. Message credibility was assessed. Afterwards
      participants completed measures of intentions to drink responsibly and we
      measured usual drinking habits and perceptions of peer drinking. RESULTS:
      Perceptions of peer drinking were associated modestly with usual drinking
      behavior, whereby participants who believed other students drank responsibly also
      drank responsibly. Norm messages changed normative perceptions, but not in the
      target population of participants who underestimated responsible drinking in
      their peers at baseline. Norm messages did not increase intentions to drink
      responsibly and although based on accurate data, norm messages were not seen as
      credible. CONCLUSIONS: In this UK based study, although perceived social norms
      about peer drinking were associated with individual differences in drinking
      habits, campus wide norm messages about responsible drinking did not affect
      students' intentions to drink more responsibly. More research is required to
      determine if this approach can be applied to UK settings.

PMID- 24730565
TI  - Self-control as a moderator of the relationship between drinking identity and
      alcohol use.
AB  - This study evaluated self-control in the relationship between drinking identity
      and drinking. We expected those higher in drinking identity would drink more than
      those lower in drinking identity, particularly if low in self-control. Data were
      collected in 2012 via an online survey (N = 690 undergraduates, M age = 22.87, SD
      = 5.37, 82.50% female) at an urban university. An interaction emerged between
      self-control and drinking identity; self-control was negatively associated with
      drinking among individuals low in drinking identity, but positively associated
      with drinking among those high in drinking identity. Implications and future
      directions are discussed. This research was unfunded. 

PMID- 24730566
TI  - Health information seeking and the World Wide Web: an uncertainty management
      perspective.
AB  - Uncertainty management theory was applied in the present study to offer one
      theoretical explanation for how individuals use the World Wide Web to acquire
      health information and to help better understand the implications of the Web for
      information seeking. The diversity of information sources available on the Web
      and potential to exert some control over the depth and breadth of one's
      information-acquisition effort is argued to facilitate uncertainty management. A
      total of 538 respondents completed a questionnaire about their uncertainty
      related to cancer prevention and information-seeking behavior. Consistent with
      study predictions, use of the Web for information seeking interacted with
      respondents' desired level of uncertainty to predict their actual level of
      uncertainty about cancer prevention. The results offer evidence that respondents
      who used the Web to search for cancer information were better able than were
      respondents who did not seek information to achieve a level of uncertainty
      commensurate with the level of uncertainty they desired. 

PMID- 24730567
TI  - Histopathological, immunohistochemical and molecular cytogenetic analysis of 21
      spindle cell/sclerosing rhabdomyosarcomas.
AB  - Recently, spindle cell/sclerosing rhabdomyosarcoma (RMS) has been recognized as
      another distinct variant of a RMS. We evaluated clinicopathological features of
      21 cases of spindle cell and sclerosing RMS and performed fluorescent in situ
      hybridization (FISH) testing in 10 (47.6%) tumours. Twenty-one tumours occurred
      in 16 males and 5 females (mean age, 19.7 years); commonly in the head and neck
      region (8) (38%) and extremities (7) (33.3%), followed by paratesticular region
      (2) (9.5%), chest wall (1), abdomen (1), pelvis (1) and paraspinal region (1).
      Average tumour size was 7.9 cm. Histopathologically, tumours that were spindle
      cell type (8) (38%) mostly occurred in the head and neck region, while sclerosing
      type (10) (47.6%) mostly occurred in the extremities. Remaining three (14.2%)
      tumours were mixed (sclerosing with spindle cell type). Tumour areas resembling
      embryonal RMS (ERMS) and alveolar RMS (ARMS) were noted in eight and three
      tumours respectively. Immunohistochemically, tumour cells were positive for
      desmin (21/21) (100%), MyoD1 (19/19) (100%), myogenin (13/15) (86.6%), SMA (2/3)
      and MIC2 (1/8) (12.5%). On FISH testing, none of the 10 tumours exhibited RMS1
      (PAX3-FOXO1) or RMS 2 (PAX7-FOXO1) fusion. Eighteen patients underwent surgical
      resection and were offered adjuvant chemotherapy (CT) (4 cases), adjuvant CT +
      radiotherapy (RT) (4 cases) and adjuvant RT (1 case). Two patients underwent CT
      and a single patient received CT + RT. On follow-up (16 cases) (2-36 months), six
      tumours recurred and nine metastasized. Spindle/sclerosing RMSs are aggressive
      tumours and occur commonly in the head and neck and extremity sites. These
      tumours are histopathologically interrelated. Their immunohistochemical and
      cytogenetic profile is closer to ERMS than ARMS. 

PMID- 24730568
TI  - Trait of routinization and adaptation to life in continuing care communities
      among older adults in Israel.
AB  - AIM: To examine the relationship between levels of adaptation to independent
      living in continuing care communities and the personality trait, routinization.
      METHODS: Using a correlative design, structured face-to-face interviews were
      carried out with 120 older adults residing in independent housing units across
      six continuing care facilities in Israel, using the Index of Relocation
      Adjustment and the Variety Assessment Scale questionnaires. RESULTS: In a mixed
      model, one of the two routinization subscales (disliking disruption) was
      moderately associated with adaptation, controlling for decision to enter the
      facility, satisfaction with the facility, family relationship, functional status,
      education, family status and type of setting. Residents who expressed high levels
      of disliking disruption, higher functional status and less involvement in the
      decision to enter the facility reported poorer adaptation to their living
      conditions. CONCLUSION: Our findings point out the complexity and intricacy of
      personal attributes as factors associated with adaptation to transitions in older
      age, and highlight the potential contribution of the trait of routinization to
      adaptation. Further research is required to identify ways to best support older
      adult transitions to institutional environments, considering different
      personality traits and environments.

PMID- 24730569
TI  - Significance of the melanocortin 1 receptor in the DNA damage response of human
      melanocytes to ultraviolet radiation.
AB  - Activation of the melanocortin 1 receptor (MC1R) by alpha-melanocortin (alpha
      MSH) stimulates eumelanin synthesis and enhances repair of ultraviolet radiation
      (UV)-induced DNA damage. We report on the DNA damage response (DDR) of human
      melanocytes to UV and its enhancement by alpha-MSH. alpha-MSH up-regulated the
      levels of XPC, the enzyme that recognizes DNA damage sites, enhanced the UV
      induced phosphorylation of the DNA damage sensors ataxia telangiectasia and Rad3
      related (ATR) and ataxia telangiectasia mutated (ATM) and their respect-ive
      substrates checkpoint kinases 1 and 2, and increased phosphorylated H2AX
      (gammaH2AX) formation. These effects required functional MC1R and were absent in
      melanocytes expressing loss of function (LOF) MC1R. The levels of wild-type p53
      induced phosphatase 1 (Wip1), which dephosphorylates gammaH2AX, correlated
      inversely with gammaH2AX. We propose that alpha-MSH increases UV-induced
      gammaH2AX to facilitate formation of DNA repair complexes and repair of DNA
      photoproducts, and LOF of MC1R compromises the DDR and genomic stability of
      melanocytes.

PMID- 24730570
TI  - Pushing the theoretical limit of Li-CF(x) batteries: a tale of bifunctional
      electrolyte.
AB  - In a typical battery, the inert electrolyte functions solely as the ionic
      conductor without contribution to the cell capacity. Here we demonstrate that the
      most energy-dense Li-CF(x) battery delivers a capacity exceeding the theoretical
      maximum of CF(x) with a solid electrolyte of Li3PS4 (LPS) that has dual
      functions: as the inert electrolyte at the anode and the active component at the
      cathode. Such a bifunctional electrolyte reconciles both inert and active
      characteristics through a synergistic discharge mechanism of CF(x) and LPS. The
      synergy at the cathode is through LiF, the discharge product of CF(x), which
      activates the electrochemical discharge of LPS at a close electrochemical
      potential of CF(x). Therefore, the solid-state Li-CF(x) batteries output 126.6%
      energy beyond their theoretic limits without compromising the stability of the
      cell voltage. The additional energy comes from the electrochemical discharge of
      LPS, the inert electrolyte. This bifunctional electrolyte revolutionizes the
      concept of conventional batteries and opens a new avenue for the design of
      batteries with unprecedented energy density.

PMID- 24730571
TI  - Experiences of teen drivers and their advice for the learner license phase.
AB  - OBJECTIVE: Teen drivers remain at considerable risk of injury and fatality during
      the earliest years of independent driving. Multistage licensing programs, such as
      graduated driver licensing (GDL), have been implemented in numerous jurisdictions
      as a form of exposure control, mandating minimum practice periods and driving
      restrictions such as night driving and passenger limits. However, the teen
      driver's experiences of GDL during the learner phase, and the driving and other
      advice they recommend be shared with all learners, remains unknown at this time.
      METHODS: Thirty-seven learner drivers (aged 16-18 years, mean = 16.7, mode = 16;
      9 males) from 2 high schools (one private, 3 males; one public) participated in
      one of 2 (group 1: private school, n = 17) 45-min group discussions. RESULTS: Two
      themes emerged: (1) learning to drive and (2) supervision of the learner driver.
      A wealth of experiences and advice pertaining to the subthemes of supervisor
      behavior, GDL, road environment, vehicle logistics, and interacting with other
      road users were shared by learners. Numerous recommendations are made pertaining
      to each subtheme, such as clear instruction and feedback, tips for negotiating
      complex infrastructure, and normalizing of outcomes like stalled vehicles when
      first learning to drive. Furthermore, it appears that current approaches of
      issuing supporting literature at the commencement of the learner phase are
      insufficient. CONCLUSIONS: The wealth of experiences and advice shared by the
      learner drivers should be considered in refining the content and process of the
      learner license phase. Moreover, the nonuse of learner resources suggests that
      alternative mechanisms of engagement and information dissemination need to be
      explored.

PMID- 24730572
TI  - The F type mitochondrial genome of hard-shelled mussel: Mytilus coruscus
      (Mytiloida, Mytilidae).
AB  - We determined the complete mitochondrial genome of the female hard-shelled mussel
      Mytilus coruscus (Gould, 1869) (F type). The F type genome is composed of 16,642
      bp in length including 12 protein coding genes (PCGs), 2 rRNA and 23 tRNA with
      the same gene content and order as the other Mytilus species which is
      characterized by the absence of the ATPase8 gene and addition of tRNA(Met) (AUA).
      The nucleotide composition of the genome shows that the percentage of A+T (63.2%)
      is higher than those of M. edulis complex species (M. edulis, M.
      galloprovincialis, M. trossulus) but lower than that of M. californianus. The F
      type mitochondrial genome of M. coruscus will provide useful information on the
      evolutionary history of the Mytilus species in the family Mitilidae.

PMID- 24730573
TI  - A Refined Model of the HCV NS5A protein bound to daclatasvir explains drug
      resistant mutations and activity against divergent genotypes.
AB  - Many direct-acting antiviral agents (DAAs) that selectively block hepatitis C
      virus (HCV) replication are currently under development. Among these agents is
      Daclatasvir, a first-in-class inhibitor targeting the NS5A viral protein.
      Although Daclatasvir is the most potent HCV antiviral molecule yet developed, its
      binding location and mode of binding remain unknown. The drug exhibits a low
      barrier to resistance mutations, particularly in genotype 1 viruses, but its
      efficacy against other genotypes is unclear. Using state-of-the-art modeling
      techniques combined with the massive computational power of Blue Gene/Q, we
      identified the atomic interactions of Daclatasvir within NS5A for different HCV
      genotypes and for several reported resistant mutations. The proposed model is the
      first to reveal the detailed binding mode of Daclatasvir. It also provides a tool
      to facilitate design of second generation drugs, which may confer less resistance
      and/or broader activity against HCV. 

PMID- 24730574
TI  - Social support and depressive symptoms among caregivers of veterans with multiple
      sclerosis.
AB  - PURPOSE/OBJECTIVE: The primary aim of this study was to examine the relationship
      between perceived social support and depressive symptoms among family caregivers
      of veterans with multiple sclerosis (MS). A secondary aim of this study was to
      examine the relationship between caregiver perceived social support and caregiver
      demographic variables, veteran health-related variables, and caregiver depressive
      symptoms. RESEARCH METHOD/DESIGN: As part of a larger study, 42 family caregivers
      of veterans with MS completed questionnaires by telephone. Hierarchical
      regression was used to examine the relationship between caregiver depressive
      symptoms and perceived social support. RESULTS: Greater MS disease severity and
      poorer overall veteran health were associated with higher levels of depressive
      symptoms among caregivers. Caregiver perceived social support was associated with
      depressive symptoms after controlling for veterans' MS disease severity and
      overall physical health. CONCLUSIONS/IMPLICATIONS: Psychosocial interventions
      aimed at enhancing social support among caregivers of veterans with MS in
      multiple life domains, such as work, finances, housing, social life, marriage,
      and family, may be important for family caregiver mood management, particularly
      as MS disease severity increases.

PMID- 24730575
TI  - Evaluation of an online health promotion program for vocational rehabilitation
      consumers.
AB  - PURPOSE/OBJECTIVE: The purpose of this study was to test the comparative
      effectiveness of three variations of an online-based health promotion program for
      improving health and employment outcomes in a sample of Vocational Rehabilitation
      consumers. RESEARCH METHOD/DESIGN: A total of 222 VR consumers participated in a
      randomized trial of three health promotion variations and provided baseline, 2-,
      4-, and 6-month data. Data were analyzed using repeated measures ANOVA. The three
      health promotion variations included (a) FACTSHEETS-a series of four electronic
      factsheets; (b) HPE-an online interactive health promotion website that included
      health behavior content and tailored action planning, and (c) HPE + MI-the online
      health promotion website plus two 30-minute calls with a trained motivational
      interviewer. RESULTS: Contrary to expectations, evidence did not support between
      group differences based on intervention intensity. In fact, the Factsheet, HPE,
      and HPE + MI participants all experienced significant reductions in secondary
      conditions, F(2.85, 489) = 7.808, p < .001, HRQoL symptom days, F(2.7, 495) =
      4.795, p = .004; and significant improvements in healthy lifestyle behaviors,
      F(2.6, 495) = 3.66, p = .017 over the 6-month study period. Although this study
      did not include a control group, a control group from another study with a
      similar population did not experience similar outcomes. CONCLUSION/IMPLICATIONS:
      People with disabilities experience significantly higher rates of secondary
      health conditions and lower employment rates than people without disabilities.
      The combination of these factors signifies the need for health promotion
      programming outside the work setting.

PMID- 24730576
TI  - An organotrifluoroborate-based convergent total synthesis of the potent cancer
      cell growth inhibitory depsipeptides kitastatin and respirantin.
AB  - The total syntheses of the highly cytotoxic neo-antimycin macrocyclic
      depsipeptide natural products kitastatin and respirantin have been accomplished
      in a convergent manner using MNBA promoted esterifications and an efficient C-
      and N-terminus bis-deprotection/HATU promoted macrolactamization. The first
      examples of using a prenyltrifluoroborate reagent in additions to carbonyl groups
      are disclosed including a diastereoselective multigram scale montmorillonite K10
      catalyzed prenylation of N-Boc-l-leucinal to install the structurally unique gem
      dimethyl-beta-keto-ester fragment. 

PMID- 24730577
TI  - Assessment of safety of non-anesthesiologist-assisted endoscopic retrograde
      cholangiopancreatography based on performance status in elderly patients.
AB  - BACKGROUND AND AIM: Endoscopic retrograde cholangiopancreatography (ERCP) has
      been increasingly performed in the elderly patients, yet little is known
      concerning objective criteria of safety. This study aimed to determine the
      potential predictors for the procedure-related outcomes. METHODS: Two hundred
      eighty-one patients older than 70 years who were indicated for ERCP (group A [n =
      195], 70-79 years of age; group B [n = 86], >= 80 years of age) were
      prospectively enrolled and analyzed for the development of serious adverse events
      related to ERCP. RESULTS: ERCP was not performed in six patients at high risk for
      the procedure. There were significant differences between group A and B in Duke
      Activity Status Index (DASI) (23.1 vs 14.9, P < 0.01) and Eastern Cooperative
      Oncology Group performance status (3 and 4, 49/195 vs 33/86, P < 0.05). Major
      ERCP-related complications (hypotension, severe bradycardia, hypoxia, myocardial
      infarction, cerebral infarction) occurred in five patients from group B and three
      from group A. Post-ERCP pancreatitis occurred in one patient from group A and
      bleeding in one from group B. In univariate analysis, old age (>= 80 years),
      American Society of Anesthesiologists score >= 3, and DASI < 10 were
      statistically significant predictors for overall serious events related to ERCP.
      In the multivariate analysis, DASI < 10 (only manage to ambulate) was independent
      predictor for overall serious events related to ERCP. CONCLUSION: DASI score is
      useful predictor for the feasibility assessment of safe ERCP in the elderly
      patients.

PMID- 24730578
TI  - Isolation of cellular membranes from lignin-producing tissues of Norway spruce
      and analysis of redox enzymes.
AB  - There are no earlier reports with successful isolation of plasma membranes from
      lignin-forming tissues of conifers. A method to isolate cellular membranes from
      extracellular lignin-producing tissue-cultured cells and developing xylem of
      Norway spruce was optimized. Modifications to the homogenization buffer were
      needed to obtain membranes from these phenolics-rich tissues. Membranes were
      separated by aqueous polymer two-phase partitioning. Chlorophyll a determination,
      marker enzyme assays and western blot analyses using antibodies for each membrane
      type showed that mitochondrial, chloroplastic and to a certain extent also ER and
      Golgi membranes were efficiently diminished from the upper phase, but tonoplast
      and plasma membranes distributed evenly between the upper and lower phases. Redox
      enzymes present in the partially purified membrane fractions were assayed in
      order to reveal the origin of H(2)O(2) needed for lignification. The membranes of
      spruce contained enzymes able to generate superoxide in the presence of NAD(P)H.
      Besides members of the flavodoxin and flavodoxin-like family proteins, cytochrome
      b5, cytochrome P450 and several stress responsive proteins were identified by
      nitroblue tetrazolium staining of isoelectric focusing gels and by mass
      spectrometry. Naphthoquinones juglone and menadione increased superoxide
      production in activity-stained gels. Some juglone-activated enzymes were
      preferentially using NADH. With NADH, menadione activated only some of the
      enzymes that juglone did, whereas with NADPH the activation patterns were
      identical. Duroquinone, a benzoquinone, did not affect superoxide production.
      Superoxide dismutase, ascorbate peroxidase, catalase and an acidic class III
      peroxidase isoenzyme were detected in partially purified spruce membranes. The
      possible locations and functions of these enzymes are discussed.

PMID- 24730579
TI  - Effect of laser phototherapy (lambda660 nm) on type I and III collagen expression
      during wound healing in hypothyroid rats: an immunohistochemical study in a
      rodent model.
AB  - OBJECTIVE: The aim of this study was to assess, immunohistochemically, the impact
      of hypothyroidism and the effect of laser phototherapy on the expression of type
      I and III collagen during wound healing. BACKGROUND DATA: Hypothyroidism has been
      associated with the disruption of the body's metabolism, including the healing
      process. Laser phototherapy has been shown to be effective in improving wound
      healing, but its usefulness on enhancing wound healing under hypothyroid
      condition remains unknown. MATERIALS AND METHODS: Using general anesthesia, a
      standard surgical wound (1 cm(2)) was created on the dorsa of 48 Wistar rats
      divided into four groups of 12 animals each: control euthyroid (EC), euthyroid
      plus laser (EL), control hypothyroid (HC), and hypothyroid plus laser (HL). The
      irradiation with laser GaAlAs [lambda660 nm, 40 mW, 1 W/cm(2), continuous wave
      (CW), o=0.04 cm(2)] started immediately after surgery and was repeated every
      other day until end-point of study was reached, and animals were euthanized
      (i.e., 7 and 14 days). Laser light was applied on four different points (6 J, 150
      sec and 150 J/cm(2) per point). Hypothyroidism was induced in rats with
      propylthiouracil (0.05 g/100 mL) administered orally for 4 weeks and maintained
      until the end of the experiment. Immunohistochemistry for collagen I and III was
      performed with EnVision(TM) in the specimens removed. RESULTS: Seven days after
      the surgery EC, EL, and HL groups showed higher immunoexpression of collagen I
      and lower immunoexpression of collagen III in the newly formed tissue. There was
      increased immunoexpression of collagen I in EC when compared with HC (p=0.019).
      The immunoexpression of collagen III was significantly lower in EL than in EC
      (p=0.047) and HL (p=0.019). No significant difference was found in the
      experimental period of 14 days among the groups. CONCLUSIONS: Laser light therapy
      performed with the parameters of this investigation increased immunoexpression of
      collagen type I during tissue repair, and improved the quality of newly formed
      tissue in the presence of hypothyroidism.

PMID- 24730584
TI  - The survey of the use of QSAR methods to determine intestinal absorption and oral
      bioavailability during drug design.
AB  - Only 10% of all compounds developed by pharmaceutical companies make it to the
      market. Of the 90% that do not make it to the market, 50% either have toxicity or
      pharmacokinetic issues. Thus, the need for ADMET (absorption, distribution,
      metabolism, excretion and toxicity) optimization during the early stages of drug
      development is clear. In silico tools may be promising for this use due to their
      lower cost and time requirements. This review aims to evaluate the predictive
      power of intestinal absorption and oral bioavailability prediction methods using
      different statistical approaches over time. Improvement, refinement and
      diversification of these methods have been observed over the past few years.
      Nevertheless, some elements related to the quality of the biological data,
      disclosure of the data used and description of validation methods, that could
      contribute to building new, better and more reliable models have been ignored by
      researchers or restricted by the technical limitations of various laboratories. 

PMID- 24730580
TI  - Noncompetitive inhibition of indolethylamine-N-methyltransferase by N,N
      dimethyltryptamine and N,N-dimethylaminopropyltryptamine.
AB  - Indolethylamine-N-methyltransferase (INMT) is a Class 1 transmethylation enzyme
      known for its production of N,N-dimethyltryptamine (DMT), a hallucinogen with
      affinity for various serotonergic, adrenergic, histaminergic, dopaminergic, and
      sigma-1 receptors. DMT is produced via the action of INMT on the endogenous
      substrates tryptamine and S-adenosyl-l-methionine (SAM). The biological,
      biochemical, and selective small molecule regulation of INMT enzyme activity
      remain largely unknown. Kinetic mechanisms for inhibition of rabbit lung INMT
      (rabINMT) by the product, DMT, and by a new novel tryptamine derivative were
      determined. After Michaelis-Menten and Lineweaver-Burk analyses had been applied
      to study inhibition, DMT was found to be a mixed competitive and noncompetitive
      inhibitor when measured against tryptamine. The novel tryptamine derivative, N-[2
      (1H-indol-3-yl)ethyl]-N',N'-dimethylpropane-1,3-diamine (propyl dimethyl amino
      tryptamine or PDAT), was shown to inhibit rabINMT by a pure noncompetitive
      mechanism when measured against tryptamine with a Ki of 84 MUM. No inhibition by
      PDAT was observed at 2 mM when it was tested against structurally similar Class 1
      methyltransferases, such as human phenylethanolamine-N-methyltransferase (hPNMT)
      and human nicotinamide-N-methyltransferase (hNNMT), indicating selectivity for
      INMT. The demonstration of noncompetitive mechanisms for INMT inhibition implies
      the presence of an inhibitory allosteric site. In silico analyses using the
      computer modeling software Autodock and the rabINMT sequence threaded onto the
      human INMT (hINMT) structure (Protein Data Bank entry 2A14 ) identified an N
      terminal helix-loop-helix non-active site binding region of the enzyme. The
      energies for binding of DMT and PDAT to this region of rabINMT, as determined by
      Autodock, were -6.34 and -7.58 kcal/mol, respectively. Assessment of the
      allosteric control of INMT may illuminate new biochemical pathway(s) underlying
      the biology of INMT. 

PMID- 24730585
TI  - Fasting and post-prandial glucagon like peptide 1 and oral contraception in
      polycystic ovary syndrome.
AB  - OBJECTIVE: We aimed to investigate whether fasting and meal regulated glucagon
      like peptide 1 (GLP-1) secretion are altered in patients with polycystic ovary
      syndrome (PCOS) compared to healty women and whether oral contraceptive use
      influence GLP-1 secretion dynamics in the syndrome. DESIGN: Prospective
      observational study. PATIENTS: Fourteen lean normal glucose tolerant patients
      with PCOS and 11 age- and body mass index (BMI)-matched healthy women.
      MEASUREMENTS: Glucagon like peptide 1, glucose and insulin levels were measured
      during a standardized meal tolerance test and area under the curves (AUCs) were
      calculated. Whereas healthy controls were assessed at baseline, all tests were
      repeated in women with PCOS after treatment with ethinyl estradiol 30
      MUg/drospirenone 3 mg (EE/DRSP) for 3 months. RESULTS: Both fasting and post-meal
      levels of GLP-1 were significantly reduced in women with PCOS compared to
      controls (P = 0.022 and P = 0.028, respectively). AUC for GLP-1 was also lower in
      PCOS (P = 0.012). Glucose and insulin measurements did not show a significant
      change between the groups. In the PCOS group, GLP-1, glucose and insulin levels
      did not show any change after 3 months of EE/DRSP use. CONCLUSION: GLP-1 levels
      both at fasting and in response to a meal are blunted in lean women with PCOS
      compared to healthy women. Short term oral contraception do not alter GLP-1
      secretion in PCOS. Disturbance in incretin secretion dynamics might contribute to
      the risk of impaired glucose tolerance and type 2 diabetes in PCOS.

PMID- 24730586
TI  - Systematic review of long-acting injectables versus oral atypical antipsychotics
      on hospitalization in schizophrenia.
AB  - OBJECTIVE: To assess the impact of long-acting injectables (LAIs) versus oral
      antipsychotics (OAs) on hospitalizations among patients with schizophrenia by
      conducting a systematic literature review of studies with different study designs
      and performing a meta-analysis. METHODS: Using the PubMed database and major
      psychiatric conference proceedings, a systematic literature review for January
      2000 to July 2013 was performed to identify English-language studies evaluating
      schizophrenia patients treated with atypical antipsychotics. Studies reporting
      hospitalization rates as a percentage of patients hospitalized or as the number
      of hospitalizations per person per year were selected. The primary meta-analysis
      assessed the percentage decrease in hospitalization rates before and after
      treatment initiation for matched time periods. The secondary meta-analysis
      assessed the absolute rate of hospitalization during follow-up. Pooled treatment
      effect estimates were calculated using random-effects models. To account for
      differences in patient and study-level characteristics between studies, meta
      regression analyses were used. Subset analyses further explored the heterogeneity
      across study designs. RESULTS: Fifty-eight studies evaluating 25 arms (LAIs: 13
      arms, 4516 patients; OAs: 12 arms, 23,516 patients) in the primary meta-analysis
      and 78 arms (LAIs: 12 arms, 4481 patients; OAs: 66 arms, 96,230 patients) in the
      secondary meta-analysis were identified. Reduction in hospitalization rates for
      LAIs was 20.7 percentage points higher than that of OAs (random-effects
      estimates: LAIs = 56.2% vs. OAs = 35.5%, P = 0.023). Controlling for patient and
      study characteristics, the adjusted percentage reduction in hospitalization rates
      for LAIs was 26.4 percentage points higher than for OAs (95% CI: 3.3-49.5, P =
      0.027). As for the secondary meta-analysis, no significant difference between
      LAIs and OAs was observed (random-effects estimate: -8.6, 95% CI: -18.1-1.0, P =
      0.077). Subset analyses across type of study yielded consistent results.
      Limitations of this analysis include the long observation period, which may not
      reflect current treatment patterns, the use of all-cause hospitalization, which
      may not be solely related to schizophrenia, and the fact that most studies in the
      LAI cohort evaluated risperidone. CONCLUSION: The primary results of this meta
      analysis, including studies with both interventional and non-interventional
      designs and using meta-regressions, suggest that LAIs are associated with higher
      reductions in hospitalization rates for schizophrenia patients compared to OAs.

PMID- 24730587
TI  - Multicolor fluorescence nanoscopy by photobleaching: concept, verification, and
      its application to resolve selective storage of proteins in platelets.
AB  - Fluorescence nanoscopy provides means to discern the finer details of protein
      localization and interaction in cells by offering an order of magnitude higher
      resolution than conventional optical imaging techniques. However, these super
      resolution techniques put higher demands on the optical system and the
      fluorescent probes, making multicolor fluorescence nanoscopy a challenging task.
      Here we present a new and simple procedure, which exploits the photostability and
      excitation spectra of dyes to increase the number of simultaneous recordable
      targets in STED nanoscopy. We use this procedure to demonstrate four-color STED
      imaging of platelets with <=40 nm resolution and low crosstalk. Platelets can
      selectively store, sequester, and release a multitude of different proteins, in a
      manner specific for different physiological and disease states. By applying
      multicolor nanoscopy to study platelets, we can achieve spatial mapping of the
      protein organization with a high resolution for multiple proteins at the same
      time and in the same cell. This provides a means to identify specific platelet
      activation states for diagnostic purposes and to understand the underlying
      protein storage and release mechanisms. We studied the organization of the pro-
      and antiangiogenic proteins VEGF and PF-4, together with fibrinogen and
      filamentous actin, and found distinct features in their respective protein
      localization. Further, colocalization analysis revealed only minor overlap
      between the proteins VEGF and PF-4 indicating that they have separate storage and
      release mechanisms, corresponding well with their opposite roles as pro- and
      antiangiogenic proteins, respectively. 

PMID- 24730588
TI  - Development of the Crying Proneness Scale: associations among crying proneness,
      empathy, attachment, and age.
AB  - Crying is a unique form of human emotional expression that is associated with
      both positive and negative evocative antecedents. This article investigates the
      psychometric properties of a newly developed Crying Proneness Scale by examining
      the factor structure, test-retest reliability, and theoretically hypothesized
      relationships with empathy, attachment, age, and gender. Based on an analysis of
      data provided by a Dutch panel (Time 1: N = 4,916, Time 2: N = 4,874),
      exploratory and confirmatory factor analyses suggest that crying proneness is a
      multidimensional construct best characterized by four factors called attachment
      tears, societal tears, sentimental/moral tears, and compassionate tears. Test
      retest reliability of the scale was adequate and associations with age, gender,
      empathy, and attachment demonstrated expected relations. Results suggest that
      this scale can be used to measure crying proneness, and that it will be useful in
      future studies that aim to gain a better understanding of normal and pathological
      socioemotional development. 

PMID- 24730589
TI  - Phylogeny and size differentially influence dissolved Cd and Zn bioaccumulation
      parameters among closely related aquatic insects.
AB  - Evolutionarily distinct lineages can vary markedly in their accumulation of, and
      sensitivity to, contaminants. However, less is known about variability among
      closely related species. Here, we compared dissolved Cd and Zn bioaccumulation in
      19 species spanning two species-rich aquatic insect families: Ephemerellidae
      (order Ephemeroptera (mayflies)), generalized to be metal sensitive, and
      Hydropsychidae (order Trichoptera (caddisflies)), generalized to be metal
      tolerant. Across all species, Zn and Cd uptake rate constants (k(u)s), efflux
      rate constants (k(e)s) and bioconcentration factors (BCFs) strongly covaried,
      suggesting that these metals share transport pathways in these distinct lineages.
      K(u)s and BCFs were substantially larger in Ephemerellidae than in
      Hydropsychidae, whereas k(e)s did not dramatically differ between the two
      families. Body size played an important role in driving ku differences among
      species, but had no influence on k(e)s. While familial differences in metal
      bioconcentration were striking, each family exhibited tremendous variability in
      all bioaccumulation parameters. At finer levels of taxonomic resolution (within
      families), phylogeny did not account for differences in metal bioaccumulation.
      These findings suggest that intrafamily variability can be profound and have
      important practical implications in that we need to better understand how well
      "surrogate species" represent their fellow congeners and family members.

PMID- 24730590
TI  - Antigen-specific over-expression of human cartilage glycoprotein 39 on CD4+ CD25+
      forkhead box protein 3+ regulatory T cells in the generation of glucose-6
      phosphate isomerase-induced arthritis.
AB  - Human cartilage gp-39 (HC gp-39) is a well-known autoantigen in rheumatoid
      arthritis (RA). However, the exact localization, fluctuation and function of HC
      gp-39 in RA are unknown. Therefore, using a glucose-6-phosphate isomerase (GPI)
      induced model of arthritis, we investigated these aspects of HC gp-39 in
      arthritis. The rise in serum HC gp-39 levels was detected on the early phase of
      GPI-induced arthritis (day 7) and the HC gp-39 mRNA was increased significantly
      on splenic CD4(+) T cells on day7, but not on CD11b(+) cells. Moreover, to
      identify the characterization of HC gp-39(+) CD4(+) T cells, we assessed the
      analysis of T helper (Th) subsets. As a result, HC gp-39 was expressed dominantly
      in CD4(+) CD25(+) forkhead box protein 3 (FoxP3)(+) refulatory T cells (T(reg)),
      but not in Th1, Th2 or Th17 cells. Furthermore, to investigate the effect of HC
      gp-39 to CD4(+) T cells, T cell proliferation assay and cytokine production from
      CD4(+) T cells using recombinant HC gp-39 was assessed. We found that GPI
      specific T cell proliferation and interferon (IFN)-gamma or interleukin (IL)-17
      production were clearly suppressed by addition of recombinant HC gp-39. Antigen
      specific over-expression of HC gp-39 in splenic CD4(+) CD25(+) FoxP3(+) T(reg)
      cells occurs in the induction phase of GPI-induced arthritis, and addition of
      recombinant HC gp-39 suppresses antigen-specific T-cell proliferation and
      cytokine production, suggesting that HC gp-39 in CD4(+) T cells might play a
      regulatory role in arthritis.

PMID- 24730591
TI  - Conceptualisations of masculinity and self-reported medication adherence among
      HIV-positive Latino men in Los Angeles, California, USA.
AB  - HIV-positive Latino men have been found to have poorer medication adherence
      compared to Whites. This study sought to identify how cultural conceptualisations
      of masculinity are associated with self-reported medication adherence among
      Latino men. A total of 208 HIV-positive men reported the number of doses of
      antiretroviral medication missed in the previous seven days (dichotomised at 100%
      adherence versus less). Conceptualisations of masculinity consisted of
      traditional machismo (e.g., power and aggressive attitudes, which are normally
      associated with negative stereotypes of machismo) and caballerismo (e.g.,
      fairness, respect for elders and the importance of family). Multivariate logistic
      regression was used to identify factors associated with adherence. The mean
      adherence was 97% (SD = 6.5%; range = 57-100%). In all, 77% of the participants
      reported 100% adherence in the previous seven days. Caballerismo was associated
      with a greater likelihood (OR = 1.77; 95% CI: 1.08-2.92; p = 0.03) and machismo
      with a lower likelihood (OR = 0.60; 95% CI: 0.38-0.95; p = 0.03) of medication
      adherence. In addition, higher medication side-effects were found to be
      associated with a lower likelihood (OR = 0.59; 95% CI: 0.43-0.81; p = 0.001) of
      medication adherence. These findings reinforce the importance of identifying
      cultural factors that may affect medication adherence among HIV-positive Latino
      men resident in the USA. 

PMID- 24730592
TI  - Individual differences in trait motivational reactivity influence children and
      adolescents' responses to pictures of taboo products.
AB  - This study examined how children and adolescents respond to pictures of products
      whose use, for them, is socially or legally restricted (e.g., beer, liquor,
      cigarettes). It was theorized and found that these pictures, referred to as
      taboo, elicit an automatic motivational activation whose direction and intensity
      are influenced by age and individual differences in defensive system activation.
      Results show that 11-12-year-old children demonstrate primarily aversive
      responses to taboo products, 13-15-year-old children have less aversive
      responses, and 16-17-year-old children have mixed appetitive and aversive
      motivational responses. Further, those with high defensive system activation show
      larger aversive and smaller appetitive responses across the age groups. These
      results suggest that placing pictures of these products in prevention messages
      may work for the prevention goal of reduced experimentation and risk in younger
      children but against the prevention goal for the older children who may be more
      likely to be exposed to opportunities for experimentation and use. 

PMID- 24730593
TI  - Inappropriate detection of ventricular fibrillation in the presence of T-wave
      oversensing algorithm.

PMID- 24730595
TI  - Comprehensive profiling and natural variation of flavonoids in rice.
AB  - Flavonoids constitute a major group of plant phenolic compounds. While
      extensively studied in Arabidopsis, profiling and naturally occurring variation
      of these compounds in rice (Oryza sativa), the monocot model plant, are less
      reported. Using a collection of rice germplasm, comprehensive profiling and
      natural variation of flavonoids were presented in this report. Application of a
      widely targeted metabolomics method facilitated the simultaneous identification
      and quantification of more than 90 flavonoids using liquid chromatography tandem
      mass spectrometry (LC-MS/MS). Comparing flavonoid contents in various tissues
      during different developmental stages revealed tissue-specific accumulation of
      most flavonoids. Further investigation indicated that flavone mono-C-glycosides,
      malonylated flavonoid O-hexosides, and some flavonoid O-glycosides accumulated at
      significantly higher levels in indica than in japonica, while the opposite was
      observed for aromatic acylated flavone C-hexosyl-O-hexosides. In contrast to the
      highly differential accumulation between the two subspecies, relatively small
      variations within subspecies were detected for most flavonoids. Besides, an
      association analysis between flavonoid accumulation and its biosynthetic gene
      sequence polymorphisms disclosed that natural variation of flavonoids was
      probably caused by sequence polymorphisms in the coding region of flavonoid
      biosynthetic genes. Our work paves the way for future dissection of biosynthesis
      and regulation of flavonoid pathway in rice. 

PMID- 24730596
TI  - Toward a new theory of stereopsis.
AB  - Humans can obtain an unambiguous perception of depth and 3-dimensionality with 1
      eye or when viewing a pictorial image of a 3-dimensional scene. However, the
      perception of depth when viewing a real scene with both eyes is qualitatively
      different: There is a vivid impression of tangible solid form and immersive
      negative space. This perceptual phenomenon, referred to as "stereopsis," has been
      among the central puzzles of perception since the time of da Vinci. After
      Wheatstone's invention of the stereoscope in 1838, stereopsis has conventionally
      been explained as a byproduct of binocular vision or visual parallax. However,
      this explanation is challenged by the observation that the impression of
      stereopsis can be induced in single pictures under monocular viewing. Here I
      propose an alternative hypothesis that stereopsis is a qualitative visual
      experience related to the perception of egocentric spatial scale. Specifically,
      the primary phenomenal characteristic of stereopsis (the impression of "real"
      separation in depth) is proposed to be linked to the precision with which
      egocentrically scaled depth (absolute depth) is derived. Since conscious
      awareness of this precision could help guide the planning of motor action, the
      hypothesis provides a functional account for the important secondary phenomenal
      characteristics associated with stereopsis: the impression of interactability and
      realness. By linking stereopsis to a generic perceptual attribute, rather than a
      specific cue, it provides a potentially more unified account of the variation of
      stereopsis in real scenes and pictures and a basis for understanding why we can
      perceive depth in pictures despite conflicting visual signals.

PMID- 24730597
TI  - The multiattribute linear ballistic accumulator model of context effects in
      multialternative choice.
AB  - Context effects occur when a choice between 2 options is altered by adding a 3rd
      alternative. Three major context effects--similarity, compromise, and attraction-
      have wide-ranging implications across applied and theoretical domains, and have
      driven the development of new dynamic models of multiattribute and
      multialternative choice. We propose the multiattribute linear ballistic
      accumulator (MLBA), a new dynamic model that provides a quantitative account of
      all 3 context effects. Our account applies not only to traditional paradigms
      involving choices among hedonic stimuli, but also to recent demonstrations of
      context effects with nonhedonic stimuli. Because of its computational
      tractability, the MLBA model is more easily applied than previous dynamic models.
      We show that the model also accounts for a range of other phenomena in
      multiattribute, multialternative choice, including time pressure effects, and
      that it makes a new prediction about the relationship between deliberation time
      and the magnitude of the similarity effect, which we confirm experimentally.

PMID- 24730598
TI  - Belief polarization is not always irrational.
AB  - Belief polarization occurs when 2 people with opposing prior beliefs both
      strengthen their beliefs after observing the same data. Many authors have cited
      belief polarization as evidence of irrational behavior. We show, however, that
      some instances of polarization are consistent with a normative account of belief
      revision. Our analysis uses Bayesian networks to characterize different kinds of
      relationships between hypotheses and data, and distinguishes between cases in
      which normative reasoners with opposing beliefs should both strengthen their
      beliefs, cases in which both should weaken their beliefs, and cases in which one
      should strengthen and the other should weaken his or her belief. We apply our
      analysis to several previous studies of belief polarization and present a new
      experiment that suggests that people tend to update their beliefs in the
      directions predicted by our normative account.

PMID- 24730600
TI  - A signal-detection-based diagnostic-feature-detection model of eyewitness
      identification.
AB  - The theoretical understanding of eyewitness identifications made from a police
      lineup has long been guided by the distinction between absolute and relative
      decision strategies. In addition, the accuracy of identifications associated with
      different eyewitness memory procedures has long been evaluated using measures
      like the diagnosticity ratio (the correct identification rate divided by the
      false identification rate). Framed in terms of signal-detection theory, both the
      absolute/relative distinction and the diagnosticity ratio are mainly relevant to
      response bias while remaining silent about the key issue of diagnostic accuracy,
      or discriminability (i.e., the ability to tell the difference between innocent
      and guilty suspects in a lineup). Here, we propose a signal-detection-based model
      of eyewitness identification, one that encourages the use of (and helps to
      conceptualize) receiver operating characteristic (ROC) analysis to measure
      discriminability. Recent ROC analyses indicate that the simultaneous presentation
      of faces in a lineup yields higher discriminability than the presentation of
      faces in isolation, and we propose a diagnostic feature-detection hypothesis to
      account for that result. According to this hypothesis, the simultaneous
      presentation of faces allows the eyewitness to appreciate that certain facial
      features (viz., those that are shared by everyone in the lineup) are non
      diagnostic of guilt. To the extent that those non-diagnostic features are
      discounted in favor of potentially more diagnostic features, the ability to
      discriminate innocent from guilty suspects will be enhanced.

PMID- 24730601
TI  - The problem of suspended and revoked drivers who avoid detection at checkpoints.
AB  - OBJECTIVE: Although driver license suspension and revocation have been shown to
      improve traffic safety, suspended or revoked (SR) drivers who continue to drive
      which appears to be the majority-are about 3 times more likely to be involved in
      crashes and to cause a fatal crash. In California and many other U.S. states,
      drivers are typically mailed notices requesting that they surrender their
      licenses when they are SR for reasons other than driving under the influence of
      alcohol or drugs (DUI), yet they frequently do not comply. Typical procedures at
      DUI checkpoints in California and other U.S. states include inspecting driver
      licenses and checking for signs of intoxication during brief contacts with law
      enforcement officers. Hence, these checkpoints are in fact DUI/license
      checkpoints in California and many other states. The purpose of this study was to
      estimate the extent to which SR drivers avoid being detected at DUI/license
      checkpoints for SR driving, because they illegally retained possession of their
      license cards. METHOD: Law enforcement officers used electronic license card
      readers at DUI/license checkpoints in Sacramento, California, to record data for
      13,705 drivers. The SR status of all contacted drivers was determined after the
      checkpoints and compared to law enforcement citation records from the
      checkpoints. RESULTS: Although only 3% of the drivers contacted at the
      checkpoints were SR, about 41% of SR drivers were able to pass through undetected
      because they presented license cards that they illegally retained. Drivers SR for
      DUI-related reasons were more likely to be detected, whereas those SR for failure
      to provide proof of financial responsibility (insurance) were less likely to be
      detected. CONCLUSION: The fact that many SR drivers are able to pass through
      DUI/license checkpoints undetected weakens both the specific and general impacts
      of checkpoints for deterring SR driving and may diminish the effectiveness of
      suspension and revocation actions for reducing the crash risk posed by problem
      drivers. Using license card readers that can quickly identify SR drivers in real
      time during routine traffic stops and at DUI/license checkpoints warrants further
      consideration.

PMID- 24730599
TI  - Clarifying the roles of homeostasis and allostasis in physiological regulation.
AB  - Homeostasis, the dominant explanatory framework for physiological regulation, has
      undergone significant revision in recent years, with contemporary models
      differing significantly from the original formulation. Allostasis, an alternative
      view of physiological regulation, goes beyond its homeostatic roots, offering
      novel insights relevant to our understanding and treatment of several chronic
      health conditions. Despite growing enthusiasm for allostasis, the concept remains
      diffuse, due in part to ambiguity as to how the term is understood and used,
      impeding meaningful translational and clinical research on allostasis. Here, we
      provide a more focused understanding of homeostasis and allostasis by explaining
      how both play a role in physiological regulation, and a critical analysis of
      regulation suggests how homeostasis and allostasis can be distinguished. Rather
      than focusing on changes in the value of a regulated variable (e.g., body
      temperature, body adiposity, or reward), research investigating the activity and
      relationship among the multiple regulatory loops that influence the value of
      these regulated variables may be the key to distinguishing homeostasis and
      allostasis. The mechanisms underlying physiological regulation and dysregulation
      are likely to have important implications for health and disease.

PMID- 24730602
TI  - Anorganic bovine bone (ABB) vs. autologous bone (AB) plus ABB in maxillary sinus
      grafting. A prospective non-randomized clinical and histomorphometrical trial.
AB  - OBJECTIVES: This investigation focused on histological characteristics and 5-year
      implant survival after sinus floor augmentation with anorganic bovine bone (ABB,
      Bio-Oss) and ABB plus autologous bone (AB) with a ratio of 1/1. MATERIAL AND
      METHODS: Nineteen consecutive patients with bony atrophy of the posterior
      edentulous maxilla and a vertical bone height <=4 mm were prospectively included
      in this study. In the first surgical stage, the maxillary sinus was non
      randomized either augmented with ABB alone (n = 12) or a 1/1 mixture of ABB and
      AB (n = 7). After a mean healing period of 167 days, biopsies were harvested in
      the region of the grafted sinus with a trephine burr and implants were placed
      simultaneously, ABB n = 18 and ABB + AB n = 12. The samples were
      microradiographically and histomorphometrically analyzed judging the newly formed
      bone (bone volume, BV), residual bone substitute material volume (BSMV), and
      intertrabecular volume (soft tissue volume, ITV) in the region of the augmented
      maxillary sinus. Implant survival was retrospectively evaluated from patient's
      records. RESULTS: No significant difference in residual bone substitute material
      (BSMV) in the ABB group (31.21 +/- 7.74%) and the group with the mixture of ABB
      and AB (28.41 +/- 8.43%) was histomorphologically determined. Concerning the de
      novo bone formation, also both groups showed statistically insignificant
      outcomes; ABB 26.02 +/- 5.23% and ABB + AB 27.50 +/- 6.31%. In all cases,
      implants were installed in the augmented sites with sufficient primary stability.
      After a mean time in function of 5 years and 2 months, implant survival was
      93.75% in the ABB and 92.86% in the ABB + AB group with no statistically
      significant differences. CONCLUSION: The usage of ABB plus AB to a 1/1 ratio
      leads to an amount of newly formed bone comparable with the solitary use of ABB
      after grafting of the maxillary sinus. Considering that ABB is a non-resorbable
      bone substitute, it can be hypothesized that this leads to stable bone over time
      and long-term implant success. Importantly, in the sole use of ABB, bone grafting
      and therefore donor site morbidities can be avoided.

PMID- 24730603
TI  - Apolipoprotein E genotype and physical function among older people with mild
      cognitive impairment.
AB  - AIM: Mild cognitive impairment (MCI) is conceptualized as prodromal of
      Alzheimer's disease (AD). Declined physical function is one of the risk factors
      for progression to AD, whereas genetic factors, especially the apolipoprotein E
      epsilon4 allele (APOE4), also contribute to the risk of AD and affect the risk
      factors. However, the association between APOE4 and physical function in MCI is
      still unclear. To elucidate the association, we carried out the present study to
      compare physical function between APOE4 carriers and non-carriers in MCI.
      METHODS: The study included 386 MCI patients (mean age 71.6 years) who were
      classified into APOE4 carrier and non-carrier groups. The participants'
      characteristics were assessed by face-to-face interviews. Grip strength, five
      chair stand test, walking speed and 6-min walking test were measured as physical
      functions. RESULTS: In univariate analysis, the APOE4 carrier group had decreased
      walking speed compared with the non-carrier group (P < 0.05), but other measures
      of physical function were not significantly different between the groups. The
      linear regression model showed a significant association between walking speed
      and APOE4 after adjusting for covariates (P < 0.05). CONCLUSIONS: The present
      study showed that APOE4 carrier participants with MCI had decreased walking speed
      compared with non-carrier participants. Thus, APOE4 genotypes should be
      considered as a potential mediator when the measure of walking speed is used as a
      risk factor of dementia in older adults with MCI. Further studies using
      prospective data are required to clarify the relationship between physical
      function and genetic factors in MCI.

PMID- 24730605
TI  - The complete mitogenome of the Australian land crayfish Engaeus lyelli (Clark
      1936) (Crustacea: Decapoda: Parastacidae).
AB  - The complete mitochondrial genome of the enigmatic freshwater crayfish Engaeus
      lyelli was sequenced using the MiSeq Personal Sequencer (Illumina, San Diego,
      CA). The mitogenome has 16,027 bp consisting of 13 protein-coding genes, 2
      ribosomal subunit genes, 23 transfer RNAs, and a non-coding AT-rich region. The
      base composition of E. lyelli is 29.01% for T, 27.13% for C, 31.43% for A, and
      12.44% for G, with an AT bias of 60.44%. The species has the distinctive gene
      order characteristic of parastacid crayfish with the exception of some minor
      rearrangements involving the tRNA genes.

PMID- 24730604
TI  - Thermal adaptation of dihydrofolate reductase from the moderate thermophile
      Geobacillus stearothermophilus.
AB  - The thermal melting temperature of dihydrofolate reductase from Geobacillus
      stearothermophilus (BsDHFR) is ~30  degrees C higher than that of its homologue
      from the psychrophile Moritella profunda. Additional proline residues in the loop
      regions of BsDHFR have been proposed to enhance the thermostability of BsDHFR,
      but site-directed mutagenesis studies reveal that these proline residues
      contribute only minimally. Instead, the high thermal stability of BsDHFR is
      partly due to removal of water-accessible thermolabile residues such as glutamine
      and methionine, which are prone to hydrolysis or oxidation at high temperatures.
      The extra thermostability of BsDHFR can be obtained by ligand binding, or in the
      presence of salts or cosolvents such as glycerol and sucrose. The sum of all
      these incremental factors allows BsDHFR to function efficiently in the natural
      habitat of G. stearothermophilus, which is characterized by temperatures that can
      reach 75  degrees C.

PMID- 24730606
TI  - The complete mitochondrial genome of Feirana taihangnica (Anura: Dicroglossidae).
AB  - The complete mitochondrial genome sequence of the Feirana taihangnica (Anura:
      Dicroglossidae) was determined. It is a circular molecule of 17,412 bp in length,
      containing 13 protein-coding genes, 2 ribosomal RNAs, 22 transfer RNAs, and a
      control region. The tRNA(Thr) gene located in the LTPF tRNA gene cluster
      typically found in other anurans is absent from the F. taihangnica mtDNA and a
      tandem duplication of tRNA(Met) gene is observed. The A+T content of the overall
      base compositon of H-strand is 57.2% and the length of control region is 1972 bp
      with 61.8% A+T content. 

PMID- 24730607
TI  - The complete mitochondrial genome of Pampus chinensis (Perciformes:
      Stromateidae).
AB  - Long PCR and primer walking methods are employed for determining the complete
      mitochondrial genome (mitogenome) sequence of Pampus chinensis. The mitogenome is
      a circular molecule of 16,534 bp in length including the structure of 13 protein
      coding genes, 2 ribosomal RNA genes, 22 transfer RNA genes and 2 non-coding
      regions (L-strand replication origin and control region). Within the control
      region, we identify the termination-associated sequence domain (TAS), central
      conserved sequence block domains (CSB-F, CSB-E and CSB-D), and conserved sequence
      blocks (CSB-1, CSB-2 and CSB-3).

PMID- 24730608
TI  - Complete mitochondrial genome of Florida pompano Trachinotus carolinus
      (Teleostei, Carangidae).
AB  - The complete mitochondrial genome sequence of Florida pompano Trachinotus
      carolinus was determined by the overlapped polymerase chain reaction. The
      complete mitochondrial DNA sequence is 16,544 bp in length. It consists of 13
      protein-coding genes, 22 transfer RNA genes, two rRNA genes and two non-coding
      regions. Overall base composition of its mitochondrial genome is estimated to be
      28.68% for A, 16.27% for G, 26.00% for T, 29.06% for C, respectively, with a high
      A+T content (54.68%). The control region contains three conserved sequence
      blocks, a termination-associated sequence and a TATA box. The sequence data of T.
      carolinus can provide useful information for the studies on population structure,
      molecular systematic, stock evaluation and conservation genetics. It is also
      helpful to develop the rational management strategies for T. carolinus resource. 

PMID- 24730609
TI  - The complete mitochondrial genome of the striped-tailed rat-snake, Orthriophis
      taeniurus (Reptilia, Serpentes, Colubridae).
AB  - The complete mitochondrial genome (mitogenome) of the striped-tailed rat-snake
      Orthriophis taeniurus was determined in the present study. The genome is 17,183
      bp in size, containing 2 ribosomal RNA (rRNA) genes, 13 protein-coding genes
      (PCGs), 22 transfer RNA (tRNA) genes, and 2 control regions (CRI and CRII). The
      gene order and orientation in O. taeniurus mitogenome are basically identical to
      that of other alethinophidian snakes. Nucleotide composition is very similar with
      other vertebrates, showing an AT bias.

PMID- 24730610
TI  - The complete mitogenome of natural triploid Carassius auratus in Qihe River.
AB  - Qihe Carassius auratus is the territorial Carassius auratus, which is known as
      for its limited distribute in Qihe River (mainly distributed in Henan province,
      China), this species is natural triploid in China. In this study, the complete
      mitochondrial genome sequence of Carassius auratus in Qihe River has been
      obtained with PCR. The gene composition and arrangement of mitochondrial genome
      sequence of this species are similar to most of other vertebrates', which
      contains 22 tRNA genes, 13 protein-coding genes, 2 rRNA genes, and a non-coding
      control region with total length of 16,580 bp. Most of genes are encoded on Heavy
      Strand (H-strand), exclude eight tRNA and ND6 genes, which are encoded on Light
      Strand (L-strand). The bias of G and C has been found in different regions/genes
      and different statistic results. The complete mitochondrial genome sequence of
      this species would contribute to better understand population genetics,
      conservation, and the evolution of natural triploid.

PMID- 24730611
TI  - Optimization of photodynamic therapy using negative pressure.
AB  - OBJECTIVE: The goal of this study is to demonstrate an alternative procedure to
      perform topical photodynamic therapy (PDT). Here, we propose the combined use of
      negative pressure and a 5-Aminolevulinic acid (5-ALA) cream occlusion to increase
      protoporphyrin IX (PPIX) formation. BACKGROUND DATA: PDT using topical 5-ALA as a
      prodrug and precursor of PPIX has been used in the treatment and diagnosis of
      different types of cancer and skin diseases. The use of 5-ALA offers many
      advantages as a localized and non-systemic application, but it shows limitations
      in relation to skin penetration. Many authors have discussed the limitations of 5
      ALA penetration through the skin. The skin penetration of 5-ALA can be optimized
      using mechanical devices associated with typical PDT procedure. METHODS: For this
      study, 20% 5-ALA cream was applied to a 9 cm(2) area of skin, and an occlusive
      dressing was placed. The PPIX production was collected at the skin surface, using
      fluorescence spectroscopy and widefield fluorescence imaging, for 7 h, and after
      24 h. RESULTS: We observed that in the presence of negative pressure therapy, the
      PPIX production, distribution, and elimination are greater and faster than in the
      control group. The PPIX formation was ~30% in deeper skin layers, quantified by
      fluorescence spectroscopy analysis, and ~20% in surface skin layers, quantified
      by widefield fluorescence imaging analysis. CONCLUSIONS: Negative pressure
      induction can also help PDT application in the case of inefficient PPIX
      production. These results can be useful for optimizing the PDT.

PMID- 24730612
TI  - Prediction of linear cationic antimicrobial peptides based on characteristics
      responsible for their interaction with the membranes.
AB  - Most available antimicrobial peptides (AMP) prediction methods use common
      approach for different classes of AMP. Contrary to available approaches, we
      suggest that a strategy of prediction should be based on the fact that there are
      several kinds of AMP that vary in mechanisms of action, structure, mode of
      interaction with membrane, etc. According to our suggestion for each kind of AMP,
      a particular approach has to be developed in order to get high efficacy.
      Consequently, in this paper, a particular but the biggest class of AMP, linear
      cationic antimicrobial peptides (LCAP), has been considered and a newly developed
      simple method of LCAP prediction described. The aim of this study is the
      development of a simple method of discrimination of AMP from non-AMP, the
      efficiency of which will be determined by efficiencies of selected descriptors
      only and comparison the results of the discrimination procedure with the results
      obtained by more complicated discriminative methods. As descriptors the
      physicochemical characteristics responsible for capability of the peptide to
      interact with an anionic membrane were considered. The following characteristics
      such as hydrophobicity, amphiphaticity, location of the peptide in relation to
      membrane, charge density, propensities to disordered structure and aggregation
      were studied. On the basis of these characteristics, a new simple algorithm of
      prediction is developed and evaluation of efficacies of the characteristics as
      descriptors performed. The results show that three descriptors, hydrophobic
      moment, charge density and location of the peptide along the membranes, can be
      used as discriminators of LCAPs. For the training set, our method gives the same
      level of accuracy as more complicated machine learning approaches offered as CAMP
      database service tools. For the test set accuracy obtained by our method gives
      even higher value than the one obtained by CAMP prediction tools. The AMP
      prediction tool based on the considered method is available at
      http://www.biomedicine.org.ge/dbaasp/.

PMID- 24730613
TI  - Mechanochemically enhanced degradation of pyrene and phenanthrene loaded on
      magnetite.
AB  - The enhancement of the degradation of polycyclic aromatic hydrocarbons (PAHs),
      exemplified by pyrene and phenanthrene, using mild grinding in the presence of
      common minerals was investigated. Magnetite, birnessite, and Na- and Cu
      montmorillonite samples were loaded with pyrene or phenanthrene and ground
      manually or in a ball mill for short periods of time. The ground samples were
      analyzed for PAHs and for their metabolites, using high-performance liquid
      chromatography and liquid chromatography-mass spectrometry. No degradation of
      pyrene occurred when it was in contact with Na-montmorillonite or birnessite.
      Sorption of pyrene on Cu-montmorillonite enhanced its degradation, but grinding
      of the loaded clay actually inhibited pyrene's degradation. Phenanthrene hardly
      degraded on Cu-montmorillonite. Grinding magnetite loaded with either PAH
      resulted in a significant degradation of both (~50% after grinding for 5 min),
      while in the nonground samples, negligible degradation was detected. The extent
      of degradation increased with the duration of grinding. The degradation of either
      PAH loaded on magnetite yielded oxidized products. In soil samples contaminated
      with PAHs and mixed with magnetite, a similar grinding-induced degradation
      pattern was observed, but with a lower rate. A liquid phase was required to
      initiate degradation in the soil. The liquid phase apparently served as the
      medium through which the pollutants reached the surface of the degradation
      enhancing mineral. 

PMID- 24730614
TI  - Nanoimprinting techniques for large-area three-dimensional negative index
      metamaterials with operation in the visible and telecom bands.
AB  - We report advances in materials, designs, and fabrication schemes for large-area
      negative index metamaterials (NIMs) in multilayer "fishnet" layouts that offer
      negative index behavior at wavelengths into the visible regime. A simple
      nanoimprinting scheme capable of implementation using standard, widely available
      tools followed by a subtractive, physical liftoff step provides an enabling route
      for the fabrication. Computational analysis of reflection and transmission
      measurements suggests that the resulting structures offer negative index of
      refraction that spans both the visible wavelength range (529-720 nm) and the
      telecommunication band (1.35-1.6 MUm). The data reveal that these large (>75
      cm(2)) imprinted NIMs have predictable behaviors, good spatial uniformity in
      properties, and figures of merit as high as 4.3 in the visible range. 

PMID- 24730621
TI  - Surgical periodontal therapy with and without initial scaling and root planing in
      the management of chronic periodontitis: a randomized clinical trial.
AB  - AIM: To compare the outcomes of surgical periodontal therapy with and without
      initial scaling and root planing. METHODS: Twenty-four patients with severe
      chronic periodontitis were enrolled in this pilot, randomized controlled clinical
      trial. Patients were equally allocated into two treatment groups: Control group
      was treated with scaling and root planing, re-evaluation, followed by Modified
      Widman Flap surgery and test group received similar surgery without scaling and
      root planing. Clinical attachment level, probing depth and bleeding on probing
      were recorded. Standardized radiographs were analysed for linear bone change from
      baseline to 6 months. Wound fluid inflammatory biomarkers were also assessed.
      RESULTS: Both groups exhibited statistically significant improvement in clinical
      attachment level and probing depth at 3 and 6 months compared to baseline. A
      statistically significant difference in probing depth reduction was found between
      the two groups at 3 and 6 months in favour of the control group. No statistically
      significant differences in biomarkers were detected between the groups.
      CONCLUSIONS: Combined scaling and root planing and surgery yielded greater
      probing depth reduction as compared to periodontal surgery without initial
      scaling and root planing.

PMID- 24730622
TI  - Cognitive decline and brain pathology in aging--need for a dimensional, lifespan
      and systems vulnerability view.
AB  - Changes in brain structure and activity as well as cognitive function are
      commonly seen in aging. However, it is not known when aging of brain and
      cognition starts, and how much of the changes observed in seemingly healthy older
      adults that can be ascribed to incipient neurodegenerative disease. Recent
      research has yielded evidence that the borders between development and aging
      sometimes can be fuzzy, as can the borders between dementing disease and normal
      age changes. In this review, we argue that many factors affecting cognitive
      decline and dementia represents quantitative rather than qualitative differences
      in characteristics that commonly exist in the population. Further, factors known
      to affect brain and cognition in aging will often do so through a life-long
      accumulation of impact, and does not need to be specific to aging. And finally, a
      host of environmental and genetic factors and their interplay determine optimal
      aging, leaving room for potential for environmental interventions to affect the
      outcome of the aging process. Together, we argue that these factors call for a
      dimensional rather than categorical, lifespan rather than aging, and
      multidimensional systems-vulnerability rather than simple "hypothetical
      biomarker" model of age-associated cognitive decline and dementia. This has
      implications for how we should view lifespan trajectories of change in brain and
      cognitive function, and how we can study, prevent, diagnose and treat age
      associated cognitive deficits. 

PMID- 24730623
TI  - Outcome of paediatric cataract surgery with primary posterior capsulotomy and
      anterior vitrectomy using intra-operative preservative-free triamcinolone
      acetonide.
AB  - PURPOSE: To evaluate the intra-operative and postoperative outcome of paediatric
      cataract surgery with primary posterior capsulotomy (PPC) and anterior vitrectomy
      using intra-operative preservative-free triamcinolone acetonide. METHODS: In this
      prospective, interventional case-control study, 20 Children who underwent
      cataract surgery for both eyes were enrolled and their eyes were randomized into
      two groups. Group A consists of 20 eyes in which standard phacoaspiration with
      PPC with intracameral triamcinolone was used, and Group B consists of 20 eyes in
      which triamcinolone were not used. Intra-operative complications and
      postoperative outcome like intraocular pressure (IOP), posterior synechiae,
      pigment deposits and posterior capsule opacification (PCO) were studied. RESULTS:
      In both groups, age range varied between 2-8 years comprising 18 males and two
      females. The mean postoperative IOP did not show any significant variation during
      6-month follow-up. In study group, all the 20 eyes were quiet at 2 weeks, while
      there was cellular reaction 1+ in four eyes (20%) and nil in 16 eyes (80%) at 2
      week in the control group (p = 0.035). Pigment deposits on IOL optic was seen in
      two eyes (10%) of the study group while in control group, IOL deposits were
      present in 14 eyes (70%) (p = 0.001). Posterior capsule opacification was seen in
      two eyes (10%) in control group at 3 months while none occurred in study group.
      CONCLUSIONS: Intra-operative use of preservative-free triamcinolone acetonide led
      to less anterior chamber inflammation and pigment deposits on IOL optic
      postoperatively compared to those eyes where it was not used.

PMID- 24730624
TI  - A novel protocol allowing oral delivery of a protein complement inhibitor that
      subsequently targets to inflamed colon mucosa and ameliorates murine colitis.
AB  - While there is evidence of a pathogenic role for complement in inflammatory bowel
      disease, there is also evidence for a protective role that relates to host
      defence and protection from endotoxaemia. There is thus concern regarding the use
      of systemic complement inhibition as a therapeutic strategy. Local delivery of a
      complement inhibitor to the colon by oral administration would ameliorate such
      concerns, but while formulations exist for oral delivery of low molecular weight
      drugs to the colon, they have not been used successfully for oral delivery of
      proteins. We describe a novel pellet formulation consisting of cross-linked
      dextran coated with an acrylic co-polymer that protects the complement inhibitor
      CR2-Crry from destruction in the gastrointestinal tract. CR2-Crry containing
      pellets administered by gavage, were characterized using a therapeutic protocol
      in a mouse model of dextran sulphate sodium (DSS)-induced colitis. Oral treatment
      of established colitis over a 5-day period significantly reduced mucosal
      inflammation and injury, with similar therapeutic benefit whether or not the
      proton pump inhibitor, omeprazole, was co-administered. Reduction in injury was
      associated with the targeting of CR2-Crry to the mucosal surface and reduced
      local complement activation. Treatment had no effect on systemic complement
      activity. This novel method for oral delivery of a targeted protein complement
      inhibitor will reduce systemic effects, thereby decreasing the risk of
      opportunistic infection, as well as lowering the required dose and treatment cost
      and improving patient compliance. Furthermore, the novel delivery system
      described here may provide similar benefits for administration of other protein
      based drugs, such as anti-tumour necrosis factor-alpha antibodies. 

PMID- 24730625
TI  - Measurement of flow velocity and inference of liquid viscosity in a microfluidic
      channel by fluorescence photobleaching.
AB  - We present a simple, noninvasive method for simultaneous measurement of flow
      velocity and inference of liquid viscosity in a microfluidic channel. We track
      the dynamics of a sharp front of photobleached fluorescent dye using a confocal
      microscope and measure the intensity at a single point downstream of the initial
      front position. We fit an exact solution of the advection diffusion equation to
      the fluorescence intensity recovery curve to determine the average flow velocity
      and the diffusion coefficient of the tracer dye. The dye diffusivity is
      correlated to solute concentration to infer rheological properties of the liquid.
      This technique provides a simple method for simultaneous elucidation of flow
      velocity and liquid viscosity in microchannels. 

PMID- 24730626
TI  - Guidelines for medical treatment of acute Kawasaki disease: report of the
      Research Committee of the Japanese Society of Pediatric Cardiology and Cardiac
      Surgery (2012 revised version).

PMID- 24730628
TI  - Juvenile polyarteritis nodosa associated with toxoplasmosis presenting as
      Kawasaki disease.
AB  - Polyarteritis nodosa (PAN) is a vasculitis characterized by inflammatory necrosis
      of medium-sized arteries. Juvenile PAN and Kawasaki disease (KD) both cause
      vasculitis of the medium-sized arteries, and share common features. They have
      overlapping clinical features. Treatment should be managed according to the
      severity of symptoms and persistence of clinical manifestations. Herein is
      described the case of a 14-year-old boy first diagnosed with KD, who then
      fulfilled the criteria for juvenile PAN due to the development of severe myalgia,
      persistent fever, polyneuropathy and coronary arterial dilatation. He also had
      acute toxoplasmosis at the onset of vasculitis symptoms. The final diagnosis was
      of juvenile PAN associated with toxoplasmosis infection. Toxoplasma infection can
      be considered as an etiological agent for PAN and other vasculitis syndromes.
      Awareness of toxoplasmosis-related PAN facilitates early diagnosis, and
      instigation of appropriate treatment. 

PMID- 24730627
TI  - Primary ciliary dyskinesia diagnosed on nasal mucosal biopsy in two newborns.
AB  - Primary ciliary dyskinesia (PCD) is a genetic disease that causes abnormalities
      in ciliary structure and/or function. Ciliated cells line the upper and lower
      respiratory tracts and the Eustachian tube. Impairment of mucus clearance at
      these sites leads to sinusitis, repeated pulmonary infections, bronchiectasis,
      and chronic otitis media. Situs inversus occurs randomly in approximately 50% of
      subjects with PCD. The triad of situs inversus, bronchiectasis and sinusitis is
      known as Kartagener syndrome. PCD is usually an autosomal recessive disease, but
      occasional instances of X-linked transmission have been reported. Specific
      diagnosis requires examination of ciliary function or structure on light and
      electron microscopy. Early diagnosis and respiratory management are important in
      order to prevent the development of bronchiectasis and deterioration in lung
      function. We report early diagnosis of PCD on nasal mucosal biopsy in two
      newborns who presented with prolonged respiratory distress and rhinorrhea. 

PMID- 24730629
TI  - Ptosis during hematologic malignancy in children.
AB  - Neurological symptoms such as ptosis may develop due to either chemotherapeutic
      agents or involvement of the central nervous system (CNS) during hematologic
      malignancy. It is difficult to make this distinction according to clinical
      symptoms and magnetic resonance imaging findings. If the neurologic symptoms are
      increased, it is a warning of CNS involvement. Herein are described the clinical
      and neuroimaging features of three patients with hematologic malignancy who
      presented with ptosis. 

PMID- 24730630
TI  - Diagnostic challenge of large congenital liver cyst in the newborn.
AB  - Liver cysts in the newborn often pose significant diagnostic challenges.
      Described herein is a case of large congenital liver cyst that was difficult to
      diagnose both antenatally and postnatally and which was later diagnosed as Caroli
      disease. 

PMID- 24730631
TI  - Secondary pseudohypoaldosteronism causing cardiopulmonary arrest and
      cholelithiasis.
AB  - A 4-month-old boy presented with cardiopulmonary arrest on arrival after a brief
      period of lethargy. Laboratory examination indicated severe hyperkalemia,
      hyponatremia, metabolic acidosis, and slightly elevated C-reactive protein. Whole
      body computed tomography identified left-dominant hydronephrosis, hydroureter and
      cholelithiasis. Despite cardiac arrest >30 min, he was successfully resuscitated
      and treated with therapeutic hypothermia. Escherichia coli was detected on urine
      culture. Renal ultrasound showed bilateral hydronephrosis, grade II in the right
      and grade IV in the left. Retrospective analysis of the blood sample at admission
      indicated a high level of aldosterone. The patient recovered almost fully with no
      electrolyte imbalance and normal plasma renin and aldosterone, leading to the
      diagnosis of secondary pseudohypoaldosteronism associated with bilateral infected
      hydronephrosis. In this case, cholelithiasis, which may account for chronic
      dehydration, was a diagnostic clue in the absence of information of pre-existing
      situations. 

PMID- 24730632
TI  - Emergency coronary artery bypass grafting for cardiogenic shock due to left main
      coronary artery obstruction caused by Kawasaki disease in a 4-year-old boy.
AB  - We describe the case of a 4-year-old boy whose clinical course after Kawasaki
      disease resulted in coronary artery bypass grafting (CABG) due to acute
      myocardial infarction (AMI) causing cardiogenic shock. He had developed an
      ischemic cardiomyopathy due to severe localized stenosis of the left main
      coronary artery (LCA) and went into cardiogenic shock due to AMI on the day
      before a scheduled operation. He underwent successful emergency CABG within 4 h
      of MI. Postoperatively his neurological status was intact. This is the first
      report of a successful emergency CABG in a small child with cardiogenic shock due
      to LCA occlusion. CABG should be undertaken in small patients when appropriate
      indications exist, if bodyweight is >10 kg. 

PMID- 24730633
TI  - Neonatal leukemoid reaction associated with Candida albicans chorioamnionitis.
AB  - Chorioamnionitis due to Candida species is relatively rare, despite the high
      prevalence (20-25%) of Candida vulvovaginitis during pregnancy. We describe a
      case of neonatal leukemoid reaction (NLR) associated with Candida albicans
      chorioamnionitis. A male infant was born at 31 weeks' gestation and weighed 1864
      g. Laboratory tests at birth indicated marked leukocytosis (i.e. total leukocyte
      count 89.8 * 10(9) /L including 66% polymorphonuclear leukocytes and 15% band
      forms). Samples of the infant's pharyngeal mucus and tracheal aspirate were
      positive for Candida albicans. On further histopathology of the placenta, C.
      albicans mycelia had invaded the placenta, chorioamniotic membrane, and umbilical
      cord. Although it is not very common, C. albicans chorioamnionitis should be
      considered in preterm infants with NLR. 

PMID- 24730634
TI  - Perforation of enteric duplication during chemotherapy for osteosarcoma.
AB  - A 9-year-old boy undergoing chemotherapy for conventional osteosarcoma complained
      of severe abdominal pain associated with rebound tenderness and muscular defense.
      Abdominal computed tomography indicated intraperitoneal free air. On surgical
      investigation, a diverticulum-like lesion, perforated at the base, was found on
      the sidewall of the ileum. The anatomic location of the lesion was indicative of
      enteric duplication. Although the frequency of complications is very rare,
      perforations of the digestive tract should be considered in patients suffering
      severe abdominal pain while receiving chemotherapy. 

PMID- 24730635
TI  - Streptococcus gallolyticus subsp. pasteurianus meningitis in an infant.
AB  - Streptococcus gallolyticus subsp. pasteurianus was formerly classified as S.
      bovis biotype II/2, which is recognized as a rare cause of neonatal sepsis and
      meningitis. Since the taxonomy classification change, there have not been many
      reports of meningitis due to S. gallolyticus subsp. pasteurianus. Moreover, the
      pathogenesis of late onset S. gallolyticus subsp. pasteurianus meningitis in
      infants is unclear. Here we report a case of meningitis in a 5-week-old infant
      with preceding diarrhea. S. bovis biotype II/2 was isolated from the blood,
      cerebrospinal fluid and stool, and then was identified as S. gallolyticus subsp.
      pasteurianus on 16S rRNA gene sequencing. Isolates from all three sample types
      had identical profiles on pulsed-field gel electrophoresis. The intestinal tract
      was thought to be the source of the infection. 

PMID- 24730636
TI  - Biotin and carnitine deficiency due to hypoallergenic formula nutrition in
      infants with milk allergy.
AB  - Amino acid formulas and hydrolyzed formulas given to infants in Japan with milk
      allergies theoretically contain little, if any, biotin and carnitine. We assessed
      biotin and carnitine insufficiency in six infants with milk allergy who were fed
      amino acid formulas and/or hydrolyzed formulas, by measuring urine 3
      hydroxyisovaleric acid (3-HIA) and serum free carnitine (C0), respectively. All
      patients presented with elevated urine 3-HIA and lowered serum C0 compared with
      post-menstrual age-matched infants who were fed breast milk or standard infant
      formulas. Supplementation with biotin and L-carnitine immediately improved the
      insufficiency. Care should be taken to avoid biotin and carnitine deficiency in
      allergic infants fed amino acid or hydrolyzed formulas.

PMID- 24730637
TI  - Accuracy of telediagnosis of fetal heart disease using ultrasound images
      transmitted via the internet.
AB  - We verified the feasibility of telediagnosis of fetal disease by (i) grading
      telediagnosis by a pediatric cardiologist into five confidence levels; and (ii)
      comparison of fetal telediagnosis with hands-on fetal diagnosis or postnatal
      diagnosis. In 114 patients suspected of having heart disease (real time, n = 15;
      recorded image transmission, n = 99), 79 patients were in level 5 (excellent), 17
      in level 4 (good), eight in level 3 (fair), 10 in level 2 (poor), and no patients
      in level 1 (bad). The average was 4.5, and in 96 patients (84% of all)
      telediagnosis was accurate (above 4), whereas in 18 patients it was inaccurate
      (level 2 or 3). In re-examination of 25 patients, telediagnosis was confirmed in
      patients in level 4 and 5, whereas heart disease was missed in patients in levels
      2 or 3. The correct diagnosis matched the high confidence level of a specialist
      based on recognizable transmitted images. 

PMID- 24730638
TI  - Choroidal abnormalities in a 9-year-old girl with neurofibromatosis type 1.

PMID- 24730639
TI  - Author's response to letter to the editor.

PMID- 24730640
TI  - Divorce in the context of domestic violence against women in Vietnam.
AB  - This paper examines obstacles for women who face domestic violence in making
      decisions about divorce and in seeking and securing support for a divorce. The
      research was undertaken in the context of a project in one district of a coastal
      province in Vietnam that sought to reduce gender based-violence and mitigate its
      effects. Data from in-depth interviews and focus-group discussions are used to
      examine abused women's attitudes, strategies and behaviours and the responses of
      people in their communities and in the support system established by the project.
      The findings show that social norms supporting marriage discourage abused women
      from seeking divorce and, in some cases, any kind of support, and discourage
      community-based support networks, police and local court systems from providing
      effective assistance to these women. 

PMID- 24730641
TI  - Identification of Desulfobacterales as primary hydrogenotrophs in a complex
      microbial mat community.
AB  - Hypersaline microbial mats have been shown to produce significant quantities of
      H2 under dark, anoxic conditions via cyanobacterial fermentation. This flux of a
      widely accessible microbial substrate has potential to significantly influence
      the ecology of the mat, and any consumption will affect the net efflux of H2 that
      might otherwise be captured as a resource. Here, we focus on H2 consumption in a
      microbial mat from Elkhorn Slough, California, USA, for which H2 production has
      been previously characterized. Active biologic H2 consumption in this mat is
      indicated by a significant time-dependent decrease in added H2 compared with a
      killed control. Inhibition of sulfate reduction, as indicated by a decrease in
      hydrogen sulfide production relative to controls, resulted in a significant
      increase in H2 efflux, suggesting that sulfate-reducing bacteria (SRB) are
      important hydrogenotrophs. Low methane efflux under these same conditions
      indicated that methanogens are likely not important hydrogenotrophs. Analyses of
      genes and transcripts that encode for rRNA or dissimilatory sulfite reductase,
      using both PCR-dependent and PCR-independent metatranscriptomic sequencing
      methods, demonstrated that Desulfobacterales are the dominant, active SRB in the
      upper, H2-producing layer of the mat (0-2 mm). This hypothesis was further
      supported by the identification of transcripts encoding hydrogenases derived from
      Desulfobacterales capable of H2 oxidation. Analysis of molecular data provided no
      evidence for the activity of hydrogenotrophic methanogens. The combined
      biogeochemical and molecular data strongly indicate that SRB belonging to the
      Desulfobacterales are the quantitatively important hydrogenotrophs in the Elkhorn
      Slough mat.

PMID- 24730642
TI  - Violence against Chinese female sex workers from their stable partners: a
      hierarchical multiple regression analysis.
AB  - Limited data are available regarding risk factors that are related to intimate
      partner violence (IPV) against female sex workers (FSWs) in the context of stable
      partnerships. Out of the 1,022 FSWs, 743 reported ever having a stable
      partnership and 430 (more than half) of those reported experiencing IPV.
      Hierarchical multivariate regression revealed that some characteristics of stable
      partners (e.g., low education, alcohol use) and relationship stressors (e.g.,
      frequent friction, concurrent partnerships) were independently predictive of IPV
      against FSWs. Public health professionals who design future violence prevention
      interventions targeting FSWs need to consider the influence of their stable
      partners. 

PMID- 24730643
TI  - Neonatal monosodium glutamate treatment causes obesity, diabetes, and
      macrovesicular steatohepatitis with liver nodules in DIAR mice.
AB  - BACKGROUND AND AIM: Non-alcoholic steatohepatitis (NASH) is the hepatic
      manifestation of metabolic syndrome (MS). Monosodium glutamate (MSG)-treated ICR
      mice is a useful model of MS and NASH, but it shows the different patterns of
      steatosis from human NASH. Because inbred aged DIAR (ddY, Institute for Animal
      Reproduction) mice spontaneously show the similar pattern of steatosis as NASH,
      we analyzed their liver pathology after administering MSG. METHODS: MSG-treated
      DIAR mice (DIAR-MSG) and untreated DIAR mice (DIAR-controls) were sacrificed and
      assessed histopathologically at 29, 32, 40, 48, and 54 weeks of age. The NASH
      activity score, body mass index, blood glucose level, and oral glucose tolerance
      test were also assessed. RESULTS: The body mass index and blood glucose levels of
      DIAR-MSG were significantly higher than controls. The oral glucose tolerance test
      revealed a type 2 diabetes pattern in DIAR-MSG. The livers of DIAR-MSG mice
      showed macrovesicular steatosis, lobular inflammation with neutrophils, and
      ballooning degeneration after 29 weeks. At 54 weeks, mild fibrosis was observed
      in 5/6 DIAR-MSG and 2/5 DIAR-control mice. In imaging mass spectrometry analysis,
      cholesterol as well as triglyceride accumulated in the liver of DIAR-MSG mice.
      Atypical liver nodules were also observed after 32 weeks in DIAR-MSG, some with
      cellular and structural atypia mimicking human hepatocellular carcinoma. The NASH
      activity score of DIAR-MSG after 29 weeks was higher than that of control mice,
      suggesting the development of NASH. CONCLUSIONS: DIAR-MSG had NASH-like liver
      pathology and liver nodules typically associated with MS symptoms. DIAR-MSG
      provides a valuable animal model to analyze NASH pathogenesis and carcinogenesis.

PMID- 24730644
TI  - Impact of cognitive reserve on the progression of mild cognitive impairment to
      Alzheimer's disease in Japan.
AB  - AIM: The present study aimed to investigate whether cognitive reserve (CR),
      referring here to education and premorbid intelligence (IQ), is associated with
      the risk for progression from mild cognitive impairment (MCI) to Alzheimer's
      disease (AD). METHODS: A total of 51 patients with MCI and 59 patients with AD
      were prospectively enrolled for assessment with the Mini-Mental State
      Examination, the Japanese version of the cognitive subscale of the Alzheimer's
      Disease Assessment Scale, the Japanese version of the Nelson Adult Reading Test
      (JART), magnetic resonance imaging (MRI) and single-photon emission computed
      tomography (SPECT), adjusting for sex, age at diagnosis, age at onset and
      duration of illness. RESULTS: SPECT findings showed hypoperfusion in the
      posterior cingulate gyri and precunei, suggesting that the participants were in
      the early or mild stage of AD or MCI. Voxel-based morphometry MRI showed no
      statistical differences between the two groups in gray matter loss in the
      entorhinal and hippocampal areas; however, multiple logistic regression analysis
      showed a significant difference in premorbid IQ measured with JART. CONCLUSION:
      Despite the limitations of the cross-sectional design, the findings suggest that
      premorbid intellectual function might explain the discrepancy in clinical status
      between MCI and AD patients with a similar magnitude of brain pathology and
      comorbid medical disorders.

PMID- 24730645
TI  - A new epimer of ocotillol from stems and leaves of American ginseng.
AB  - A new minor C-3 epimer of ocotillol, named 3alpha-ocotillol (1), was isolated
      along with ocotillol (2) from the stems and leaves of American ginseng for the
      first time. The structure of the new sapogenin was elucidated as (20S, 24R)
      dammar-20,24-epoxy-3alpha,6alpha,12beta,25-tetraol by the combination analysis of
      NMR and mass spectrometry. The complete signal assignments of the two compounds
      were carried out by means of 2D NMR spectral analysis. 

PMID- 24730647
TI  - Catalytic asymmetric peroxidation of alpha,beta-unsaturated nitroalkenes by a
      bifunctional organic catalyst.
AB  - A new enantioselective peroxidation of alpha,beta-unsaturated nitroalkenes was
      realized with an easily accessible acid-base bifunctional organic catalyst
      derived from cinchona alkaloids. This reaction provides unprecedented easy access
      to optically active chiral peroxides, as illustrated by the asymmetric synthesis
      of beta-peroxy nitro compounds. 

PMID- 24730648
TI  - Pyrosequencing survey of intestinal microbiota diversity in cultured sea bass
      (Dicentrarchus labrax) fed functional diets.
AB  - The routine use of chemotherapy to control bacterial diseases in aquatic
      populations has resulted in the development and spread of antibiotic resistance.
      The inclusion of immunostimulants in fish diets (functional diets) is one of the
      main strategies to solve this threat. This study aimed to analyse the intestinal
      microbiota of cultured European sea bass (Dicentrarchus labrax) fed two
      functional diets applying pyrosequencing of PCR-amplified 16S rRNA gene. Quality
      filtered reads were assigned to family and genus taxonomic levels using the
      Ribosomal Database Project classifier. The autochthonous intestinal microbiota of
      sea bass consisted of two dominant bacterial genera: Dysgonomonas (Bacteroidetes)
      and Ralstonia (Betaproteobacteria), but effects of diet on this dominance were
      observed. In fact, the genus Dysgonomonas significantly decreased in samples from
      fish fed functional diets, recovering control levels at the end of the study.
      However, Ralstonia proportion significantly raised in samples from fish fed diet
      C and maintained this high level along the study period. The developed protocol
      could be used to study the composition of bacterial communities in the fish
      intestine under different nutritional and environmental conditions and its impact
      on infection, immune system and general fitness of fish. 

PMID- 24730649
TI  - A porous metal-organic framework with dynamic pyrimidine groups exhibiting record
      high methane storage working capacity.
AB  - We have realized a new porous metal-organic framework UTSA-76a with pyrimidine
      groups on the linker, exhibiting high volumetric methane uptake of ~260 cm(3)
      (STP) cm(-3) at 298 K and 65 bar, and record high working capacity of ~200 cm(3)
      (STP) cm(-3) (between 5 and 65 bar). Such exceptionally high working capacity is
      attributed to the central "dynamic" pyrimidine groups within UTSA-76a, which are
      capable of adjusting their orientations to optimize the methane packing at high
      pressure, as revealed by computational studies and neutron scattering
      experiments.

PMID- 24730650
TI  - OPDA isomerase GST16 is involved in phytohormone detoxification and insect
      development.
AB  - 12-Oxophytodienoic acid (OPDA), a well-known phytohormone of the jasmonate
      family, has a reactive alpha,beta-unsaturated carbonyl structure which easily
      adds cellular nucleophiles (Michael addition), making OPDA potentially toxic for
      herbivores. The glutathione S-transferase GST16 inactivates 12-OPDA in the insect
      gut by isomerization to inactive iso-OPDA. Quantitative tissue expression
      analysis showed that HarmGST16 transcripts were present in most larval tissues,
      including those of the midgut, fatbody and Malpighian tubules. Activity assays
      confirmed the presence of an active enzyme. Interestingly, feeding different
      diets to Helicoverpa armigera influenced gst16 expression levels in various
      tissues, and larvae fed wild-type tobacco leaves had reduced gst16 mRNA levels.
      The temporal expression of HarmGST16 during larval development was high in the
      second instar and reduced during the third, fourth and fifth instars. Plant
      mediated RNA interference silencing of HarmGST16 retarded larval growth of H.
      armigera. Injecting cis-OPDA into the hemolymph of larvae caused premature
      pupation. This result, as well as the finding that GST16 influenced the growth of
      insects, suggests that GST16 may play an important role in larval development.

PMID- 24730651
TI  - Lateral forces exerted through ball or bar attachments in relation to the
      inclination of mini-implant underneath overdentures: in vitro study.
AB  - OBJECTIVE: Lateral force to mini-implants should be avoided because mini-implants
      are weak mechanically because of its small diameter. Overdentures retained by
      mini-implants are usually formed using ball attachments. However, bar attachments
      can offer the advantage of splinting the mini-implants. This study examined the
      effect of attachments in withstanding these lateral forces in tilted mini
      implants of overdentures. MATERIALS AND METHODS: Strain gauges were attached to
      the mini-implants (2.5 * 18 mm) embedded in an acrylic resin block. Two mini
      implants were inserted vertically (Control) or with one mini-implant inclined at
      10 degrees  or 20 degrees  (10-inclined and 20-inclined, respectively). The
      female portions of the attachments were secured to the denture base. A
      prefabricated ball attachment and CAD/CAM-fabricated bar attachment were
      compared. A vertical load of 49 N was applied to the occlusal surface at a
      distance 10 mm away from the center of two mini-implants. The lateral force borne
      by the mini-implants was measured via the attached strain gauge. Mann-Whitney U
      test and an analysis of Bonferroni correction were used to compare differences
      between the two attachments and among the three models (P < 0.05). RESULTS: The
      lateral force exerted to the inclined mini-implant was significantly greater than
      that borne by a vertical mini-implant for both attachment types. The lateral
      force on the 20 degrees  inclined mini-implants with bar attachments was smaller
      than that on mini-implants with ball attachments. CONCLUSION: Inclined mini
      implants are subjected to greater stresses than vertical ones, and a bar
      attachment can reduce the lateral forces borne by the mini-implant when one mini
      implant inclined at 20 degrees .

PMID- 24730652
TI  - Structural analysis of replication protein A recruitment of the DNA damage
      response protein SMARCAL1.
AB  - SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin,
      subfamily A-like1 (SMARCAL1) is a recently identified DNA damage response protein
      involved in remodeling stalled replication forks. The eukaryotic single-strand
      DNA binding protein replication protein A (RPA) recruits SMARCAL1 to stalled
      forks in vivo and facilitates regression of forks containing leading strand gaps.
      Both activities are mediated by a direct interaction between an RPA binding motif
      (RBM) at the N-terminus of SMARCAL1 and the C-terminal winged-helix domain of the
      RPA 32 kDa subunit (RPA32C). Here we report a biophysical and structural
      characterization of the SMARCAL1-RPA interaction. Isothermal titration
      calorimetry and circular dichroism spectroscopy revealed that RPA32C binds
      SMARCAL1-RBM with a Kd of 2.5 MUM and induces a disorder-to-helix transition. The
      crystal structure of RPA32C was refined to 1.4 A resolution, and the SMARCAL1-RBM
      binding site was mapped on the structure on the basis of nuclear magnetic
      resonance chemical shift perturbations. Conservation of the interaction surface
      to other RBM-containing proteins allowed construction of a model for the
      RPA32C/SMARCAL1-RBM complex. The implications of our results are discussed with
      respect to the recruitment of SMARCAL1 and other DNA damage response and repair
      proteins to stalled replication forks. 

PMID- 24730653
TI  - "Here we're all in the same boat"--a qualitative study of group based
      rehabilitation for sick-listed citizens with chronic pain.
AB  - Musculoskeletal pain impacts upon everyday life. A degree of chronicity may pose
      an increased risk of sickness absence. One of two rehabilitative interventions,
      "Tailored Physical Activity" or "Chronic Pain Self-Management Program", was
      offered to sick-listed citizens who experienced pain. The objectives of this
      paper were to: (1) Assess what factors are experienced as problematic for sick
      listed citizens in everyday life with chronic pain, and (2) Evaluate the
      significance of two distinct rehabilitative interventions on the future everyday
      lives of sick-listed citizens. Seven semi-structured interviews with sick-listed
      citizens were analyzed using a phenomenological-hermeneutical approach. Results
      were discussed by applying the theoretical framework of Antonovsky's
      salutogenetic model and Yaloms principles for group psychology. The potential for
      development of citizen's coping is evaluated based on Roessler's notion of
      progression. The analysis revealed four main themes: (1) Living with pain and
      unemployment; (2) "Putting my foot down" and "asking for help"; (3) Significance
      of the group, including instructors, and; (4) Aspects significant to progression.
      Unemployment is a major life event that promotes stress and can be accompanied by
      problems related to depressed mood, acceptance of the life situation, feelings of
      not being useful, feelings of losing control and identity conflicts. Group
      characteristics that gave a significant basis for progression in the self
      management program are both emotional and instrumental, while the physical
      training program offers a "here-and-now"-experience and motivation to
      participate. This study indicates that the self-management program could
      potentially improve coping while the physical activity program revealed one
      example of a means of progression. 

PMID- 24730654
TI  - Photoelectron spectroscopic imaging and device applications of large-area
      patternable single-layer MoS2 synthesized by chemical vapor deposition.
AB  - Molybdenum disulfide (MoS2) films, which are only a single atomic layer thick,
      have been synthesized by chemical vapor deposition (CVD) and have gained
      significant attention due to their band-gap semiconducting properties. However,
      in order for them to be useful for the fabrication of practical devices,
      patterning processes that can be used to form specific MoS2 structures must be
      integrated with the existing synthetic approaches. Here, we report a method for
      the synthesis of centimeter-scale, high-quality single-layer MoS2 that can be
      directly patterned during CVD, so that postpatterning processes can be avoided
      and device fabrication can be streamlined. Utilizing X-ray photoelectron
      spectroscopic imaging, we characterize the chemical states of these CVD
      synthesized single-layer MoS2 films and demonstrate that the triangular-shaped
      MoS2 are single-crystalline single-domain monolayers. We also demonstrate the use
      of these high-quality and directly patterned MoS2 films in electronic device
      applications by fabricating and characterizing field effect transistors. 

PMID- 24730656
TI  - Mice with altered brain lipoprotein metabolism display maladaptive responses to
      environmental challenges that may predispose to weight gain.
AB  - BACKGROUND: Three-month-old neuron-specific lipoprotein lipase (LPL)-depleted
      mice (NEXLP(-/-)) mice are preobese and have normal body weight before developing
      obesity by 4.5 months. This series of experiments investigated responses to novel
      environment stimuli and acute sleep deprivation in preobese NEXLPL(-/-)) mice to
      test the hypothesis that neuron-specific LPL deletion alters normal adaptive
      metabolic responses to environmental challenges. METHODS: Three-month-old, age-
      and weight-matched, male NEXLPL(-/-)) (n=10) and wild-type (WT) (n=10) mice were
      housed in individual metabolic chambers with a 12-hr dark cycle. Food and water
      intake, locomotor activity, and calorimetry data were recorded in 12-min
      intervals. Novel environmental responses were elicited by first-time introduction
      to chambers at dark onset, followed by acclimation, baseline recording, and 6-hr
      of sleep deprivation on subsequent experimental days. RESULTS: NEXLPL(-/-)) mice
      displayed a 1.5-fold greater increase in activity in response to a novel
      environment than seen in WT controls (P=0.0308), and a two-fold greater increase
      in food intake following acute sleep deprivation (P=0.0117). NEXLPL(-/-)) mice
      averaged a 27% higher metabolic rate than WT mice throughout the experiments
      (P<0.0001). Body weight, composition, and temperature did not differ between
      murine groups throughout the experiments. Levels of free fatty acid, insulin,
      glucose, and triglycerides were similar between groups at the terminus.
      CONCLUSIONS: A deficiency in neuronal LPL signaling disrupts normal responses to
      novel environmental exposure and acute sleep deprivation, a maladaptive response
      that may contribute to weight gain in genetically predisposed mice, and perhaps
      humans.

PMID- 24730658
TI  - The importance of creating a social business to produce low-cost hearing aids.
AB  - The World Health Organization (WHO) estimates that about 280 million people
      worldwide have a bilateral hearing loss, mostly living in poor countries. Hearing
      loss causes heavy social burdens on individuals, families, communities and
      countries. However, due to the lack of accessibility and affordability, the vast
      majority of people in the world who need hearing aids do not have access to them.
      Low-income countries are thus pulled into a disability/poverty spiral. From this
      standpoint, the production of available, accessible and affordable hearing aids
      for the poorest populations of our planet should be one of the main issues in
      global hearing healthcare. Designing and producing a brand new low-cost hearing
      aid is the most effective option. Involving a large producer of hearing aids in
      the creation of a social business to solve the problem of access to affordable
      hearing aids is an essential step to reduce hearing disability on a large scale
      globally. Today's technology allows for the creation of a "minimal design"
      product that does not exceed $100-$150, that can be further lowered when
      purchased in large quantities and dispensed with alternative models. It is
      conceivable that by making a sustainable social business, the low cost product
      could be sold with a cross-subsidy model in order to recover the overhead costs.
      IMPLICATIONS FOR REHABILITATION: Social business is an economic model that has
      the potential to produce and distribute affordable hearing aids in low- and
      middle-income countries. Rehabilitation of hearing impaired children will be
      carried out in partnership with Sahic (Society of Assistance to Hearing Impaired
      Children) in Dhaka, Bangladesh and the ENT Department of Ospedale Burlo di
      Trieste, Dr. Eva Orzan.

PMID- 24730657
TI  - Combination of genetic screening and molecular dynamics as a useful tool for
      identification of disease-related mutations: ZASP PDZ domain G54S mutation case.
AB  - Cypher/ZASP (LDB3 gene) is known to interact with a network of proteins. It binds
      to alpha-actinin and the calcium voltage channels (LTCC) via its PDZ domain. Here
      we report the identification of a highly conserved ZASP G54S mutation classified
      as a variant of unknown significance in a sample of an adult with hypertrophic
      cardiomyopathy (HCM). The initial bioinformatics calculations strongly evaluated
      G54S as damaging. Furthermore, we employed accelerated and classical molecular
      dynamics and free energy calculations to study the structural impact of this
      mutation on the ZASP apo form and to address the question of whether it can be
      linked to HCM. Seventeen independent MD runs and simulations of 2.5 MUs total
      were performed and showed that G54S perturbs the alpha2 helix position via
      destabilization of the adjacent loop linked to the beta5 sheet. This also leads
      to the formation of a strong H-bond between peptide target residues Leu17 and
      Gln66, thus restricting both the alpha-actinin2 and LTCC C-terminal peptides to
      access their natural binding site and reducing in this way their binding
      capacity. On the basis of these observations and the adult's clinical data, we
      propose that ZASP(G54S) and presumably other ZASP PDZ domain mutations can cause
      HCM. To the best of our knowledge, this is the first reported ZASP PDZ domain
      mutation that might be linked to HCM. The integrated workflow used in this study
      can be applied for the identification and description of other mutations that
      might be related to particular diseases. 

PMID- 24730655
TI  - Class I HDACs Affect DNA Replication, Repair, and Chromatin Structure:
      Implications for Cancer Therapy.
AB  - SIGNIFICANCE: The contribution of epigenetic alterations to cancer development
      and progression is becoming increasingly clear, prompting the development of
      epigenetic therapies. Histone deacetylase inhibitors (HDIs) represent one of the
      first classes of such therapy. Two HDIs, Vorinostat and Romidepsin, are broad
      spectrum inhibitors that target multiple histone deacetylases (HDACs) and are FDA
      approved for the treatment of cutaneous T-cell lymphoma. However, the mechanism
      of action and the basis for the cancer-selective effects of these inhibitors are
      still unclear. RECENT ADVANCES: While the anti-tumor effects of HDIs have
      traditionally been attributed to their ability to modify gene expression after
      the accumulation of histone acetylation, recent studies have identified the
      effects of HDACs on DNA replication, DNA repair, and genome stability. In
      addition, the HDIs available in the clinic target multiple HDACs, making it
      difficult to assign either their anti-tumor effects or their associated
      toxicities to the inhibition of a single protein. However, recent studies in
      mouse models provide insights into the tissue-specific functions of individual
      HDACs and their involvement in mediating the effects of HDI therapy. CRITICAL
      ISSUES: Here, we describe how altered replication contributes to the efficacy of
      HDAC-targeted therapies as well as discuss what knowledge mouse models have
      provided to our understanding of the specific functions of class I HDACs, their
      potential involvement in tumorigenesis, and how their disruption may contribute
      to toxicities associated with HDI treatment. FUTURE DIRECTIONS: Impairment of DNA
      replication by HDIs has important therapeutic implications. Future studies should
      assess how best to exploit these findings for therapeutic gain.

PMID- 24730659
TI  - Intensive virtual reality-based training for upper limb motor function in chronic
      stroke: a feasibility study using a single case experimental design and fMRI.
AB  - PURPOSE: To evaluate feasibility and neurophysiological changes after virtual
      reality (VR)-based training of upper limb (UL) movements. METHOD: Single-case A-B
      A-design with two male stroke patients (P1:67 y and 50 y, 3.5 and 3 y after
      onset) with UL motor impairments, 45-min therapy sessions 5*/week over 4 weeks.
      Patients facing screen, used bimanual data gloves to control virtual arms. Three
      applications trained bimanual reaching, grasping, hand opening. Assessments
      during 2-week baseline, weekly during intervention, at 3-month follow-up (FU):
      Goal Attainment Scale (GAS), Chedoke Arm and Hand Activity Inventory (CAHAI),
      Chedoke-McMaster Stroke Assessment (CMSA), Extended Barthel Index (EBI), Motor
      Activity Log (MAL). Functional magnetic resonance imaging scans (FMRI) before,
      immediately after treatment and at FU. RESULTS: P1 executed 5478 grasps (paretic
      arm). Improvements in CAHAI (+4) were maintained at FU. GAS changed to +1 post
      test and +2 at FU. P2 executed 9835 grasps (paretic arm). CAHAI improvements
      (+13) were maintained at FU. GAS scores changed to -1 post-test and +1 at FU. MAL
      scores changed from 3.7 at pre-test to 5.5 post-test and 3.3 at FU. CONCLUSION:
      The VR-based intervention was feasible, safe, and intense. Adjustable application
      settings maintained training challenge and patient motivation. ADL-relevant UL
      functional improvements persisted at FU and were related to changed cortical
      activation patterns. Implications for Rehabilitation YouGrabber trains uni- and
      bimanual upper motor function. Its application is feasible, safe, and intense.
      The control of the virtual arms can be done in three main ways: (a) normal (b)
      virtual mirror therapy, or (c) virtual following. The mirroring feature provides
      an illusion of affected limb movements during the period when the affected upper
      limb (UL) is resting. The YouGrabber training led to ADL-relevant UL functional
      improvements that were still assessable 12 weeks after intervention finalization
      and were related to changed cortical activation patterns.

PMID- 24730662
TI  - Decomposition of nitrosamines in CO2 capture by aqueous piperazine or
      monoethanolamine.
AB  - Amine scrubbing is an efficient method for carbon capture and sequestration, but
      secondary amines present in all amine solvents can form carcinogenic
      nitrosamines. Decomposition kinetics for n-nitrosopiperazine (MNPZ),
      nitrosodiethanolamine (NDELA), and nitroso-(2-hydroxyethyl) glycine (NHeGly) were
      measured over a range of temperature, base concentration, base strength, and CO2
      loading pertinent to amine scrubbing. MNPZ and NDELA decomposition is first order
      in the nitrosamine, half order in base concentration, and base-catalyzed with a
      Bronsted slope of beta = 0.5. The activation energy is 94, 106, and 112 kJ/mol
      for MNPZ, NDELA, and NHeGly, respectively. MNPZ readily decomposes at 150 
      degrees C in 5 M piperazine, making thermal decomposition an important mechanism
      for MNPZ control. However, NHeGly and NDELA are too stable at 120  degrees C in 7
      M monoethanolamine (MEA) for thermal decomposition to be important. Base
      treatment during reclaiming could rapidly and selectively decompose NHeGly and
      NDELA to mitigate nitrosamine accumulation in MEA. 

PMID- 24730661
TI  - Biologic agents therapy for Saudi children with rheumatic diseases: indications
      and safety.
AB  - OBJECTIVE: To report the indications and safety of biologic agents in childhood
      rheumatic diseases at a tertiary hospital. METHODS: Children with rheumatic
      diseases treated with biologic agents at King Faisal Specialist Hospital and
      Research Center, Riyadh, Saudi Arabia, from January 2001 to December 2011 were
      included. All patients were reviewed for: demographic characteristics, diagnosis,
      concomitant treatment and indications of using biologic agents, age at start of
      therapy and side effects during the treatment period. RESULTS: In all, 134
      children (89 female) with various rheumatic diseases were treated with biologic
      agents. Mean age at starting biologic treatment was 9.3 (4.25-14) years and mean
      therapy duration was 14.7 (3-88) months. Juvenile idiopathic arthritis (JIA) was
      the most frequent diagnosis (70.1%) followed by systemic lupus erythematosus
      (12.7%) and vasculitis (4.5%). All patients received concomitant therapy
      (corticosteroids and disease-modifying antirheumatic drugs). In total, 273
      treatments with biologic agents were used, (95 etanercept, 52 rituximab, 47
      adalimumab, 37 infliximab, 23 anakinra, 10 tocilizumab and nine abatacept).
      Therapy was switched to another agent in 57 (42.5%) patients, mainly because of
      inefficacy (89.4%) or adverse event (10.6%). A total of 95 (34.8%) adverse events
      were notified; of these, the most frequent were infusion-related reactions
      (33.7%) followed by infections (24.2%) and autoantibody positivity (10.6%). One
      patient developed macrophage activation syndrome. CONCLUSION: Biologic agents
      were used in children with a range of rheumatic diseases. Of these, the most
      frequent was JIA. Off-label use of biologic agents in our cohort is common. These
      agents seem safe. However, they may associated with various adverse events.
      Sequential therapy seems well tolerated. However, this should be carefully
      balanced and considered on an individual basis.

PMID- 24730664
TI  - Abstracts of the 4th UK Paediatric Neuropsychology Symposium: Atypical
      Developmental Pathways, 19-23 May 2014, London, UK.

PMID- 24730660
TI  - The evolution of three decades of antiretroviral therapy: challenges, triumphs
      and the promise of the future.
AB  - The evolution of human immunodeficiency virus (HIV) treatment has improved our
      understanding and management of complex pharmacological issues that have driven
      improved outcomes and quality of life of the HIV-infected patient. These issues
      include adherence, long- and short-term toxicities, pharmacoenhancement,
      pharmacogenomics, therapeutic drug monitoring, differential penetration of drugs
      into sanctuary sites, such as the central nervous system, genital tract and small
      bowel, and drug-drug and drug-food interactions related to cytochrome P450 drug
      metabolizing enzymes, uridine diphosphate glucuronyltransferases and drug
      transporters, to name a few. There is future promise, as an increased
      understanding of the immunopathogenesis of HIV and global public health
      initiatives are driving novel treatment approaches with goals to prevent, control
      and, ultimately, eradicate HIV. 

PMID- 24730665
TI  - Liquid crystalline phase behavior of silica nanorods in dimethyl sulfoxide and
      water.
AB  - We report lyotropic smectic liquid crystalline phase behavior of silica nanorods
      dispersed in binary mixtures of dimethyl sulfoxide (DMSO) and water (H2O). The
      phase behavior is affected by nanorod size polydispersity and DMSO concentration
      in the binary solvent. The isotropic to biphasic transition is strongly affected
      by the relative amount of DMSO in the solvent, but the solvent has little effect
      on the biphasic to liquid crystal transition above 40/60 DMSO/H2O by volume. At
      less than 40% DMSO, increasing silica nanorod concentration initially results in
      the formation of liquid crystalline domains, but further increasing silica
      concentration results in crystal solvate formation. The morphology of the liquid
      crystalline phase is strongly affected by the size polydispersity, with lower
      polydispersity leading to a more uniform structure. As in other lyotropic
      nanocylinder systems, the microstructure of continuous solid films produced from
      the dispersions was affected by both the initial microstructure and the applied
      shear. 

PMID- 24730666
TI  - Corrigendum.

PMID- 24730667
TI  - Ancient DNA sheds new light on the Svalbard foraminiferal fossil record of the
      last millennium.
AB  - Recent palaeogenetic studies have demonstrated the occurrence of preserved
      ancient DNA (aDNA) in various types of fossilised material. Environmental aDNA
      sequences assigned to modern species have been recovered from marine sediments
      dating to the Pleistocene. However, the match between the aDNA and the fossil
      record still needs to be evaluated for the environmental DNA approaches to be
      fully exploited. Here, we focus on foraminifera in sediments up to one thousand
      years old retrieved from the Hornsund fjord (Svalbard). We compared the diversity
      of foraminiferal microfossil assemblages with the diversity of aDNA sequenced
      from subsurface sediment samples using both cloning and high-throughput
      sequencing (HTS). Our study shows that 57% of the species archived in the fossil
      record were also detected in the aDNA data. However, the relative abundance of
      aDNA sequence reads and fossil specimens differed considerably. We also found a
      limited match between the stratigraphic occurrence of some fossil species and
      their aDNA sequences, especially in the case of rare taxa. The aDNA data
      comprised a high proportion of non-fossilised monothalamous species, which are
      known to dominate in modern foraminiferal communities of the Svalbard region. Our
      results confirm the relevance of HTS for studying past micro-eukaryotic diversity
      and provide insight into its ability to reflect fossil assemblages. Palaeogenetic
      studies including aDNA analyses of non-fossilised groups expand the range of
      palaeoceanographical proxies and therefore may increase the accuracy of
      palaeoenvironmental reconstructions. 

PMID- 24730668
TI  - Metabolic profile of different Italian cultivars of hazelnut (Corylus avellana)
      by nuclear magnetic resonance spectroscopy.
AB  - High-resolution proton NMR spectroscopy was performed on three Italian hazelnut
      cultivars, Tonda di Giffoni, Mortarella and Tonda Gentile Romana, and it allowed
      to define their metabolic profile. The hazelnuts were grown in the same
      pedoclimatic conditions in the Monti Cimini (Latium) area. The samples were
      obtained by using a modified Bligh-Dyer extraction protocol which did not give
      rise to artefacts arising from the demolition of macromolecular structures such
      as proteins and polysaccharides. Metabolites belonging to different chemical
      classes (amino acids, organic acids, carbohydrates, lipids and miscellaneous
      compounds) were identified and quantified. The three cultivars were discriminated
      by means of univariate (ANOVA) and multivariate (PCA) statistical analysis.

PMID- 24730669
TI  - The effects of tamsulosin and alfuzosin on iris morphology: an ultrasound
      biomicroscopic comparison.
AB  - CONTEXT: It is well known that Alpha-1 adrenergic receptor antagonists affect the
      receptors in the prostate and also iris dilator muscle, leading to loss of iris
      muscle tone. OBJECTIVE: To compare morphological alterations of iris secondary to
      tamsulosin and alfuzosin use. PARTICIPANTS: Patients included in the study were
      grouped as follows: 16 patients treated with tamsulosin (Group 1), 14 patients
      treated with alfuzosin (Group 2) and 18 untreated controls (Group 3). MATERIALS
      AND METHODS: All patients underwent ultrasound biomicroscopic and pupillometric
      examination. Iris thickness was measured at the dilator muscle region (DMR;
      measured at half of the distance between the scleral spur and the pupillary
      margin) and sphincter muscle region (SMR; Standardized at 0.75 mm from the
      pupillary margin). DMR/SMR was also calculated for each patient. Differences
      among groups were analysed. Main outcome measures were DMR, SMR, DMR/SMR and
      pupillary diameter. RESULTS: Mean duration of treatments were 2.4 +/- 0.96 years
      (1-4) and 2.3 +/- 1.01 years (1-4) in Groups 1 and 2. Pupillary diameters were
      reduced in Groups 1-2 compared to Group 3 (p < 0.001, p < 0.001). The SMR was
      similar in Groups 1 and 2 (p: 0.114). These values were not significantly
      different from that of Group 3 (p: 0.196, p: 0.209). However, thickness in the
      DMR in Groups 1-2 were significantly lower than that of controls (Group 3)
      whereas there was no significant difference between Groups 1 and 2 (p: 0.041, p:
      0.039 and 0.986, respectively). Mean DMR/SMR ratios were significantly lower in
      Groups 1-2 than that of Group 3 (p: 0.040 and p: 0.040, respectively).
      CONCLUSIONS: In patients using these medications, the iris seems to be thinner at
      the dilator muscle region, but preserving the sphincter muscle region.

PMID- 24730670
TI  - Influence of Distance to Health Facilities on the Use of Skilled Attendants at
      Birth in Kenya.
AB  - We sought to determine the spatial variation in the use of skilled providers
      during deliveries across Kenya and the relationship between distance to health
      facilities and the use of skilled delivery. We found that women who resided 5 km
      or less from the nearest health facility were more likely to use skilled care at
      delivery than women residing at greater distances, although the pattern of choice
      of health facility level for delivery differed at this distance. Outreach
      maternity services are urgently required in counties with remote communities in
      order to improve access to skilled attendants during deliveries in these areas.

PMID- 24730671
TI  - Positioning of 18F-fluorodeoxyglucose-positron emission tomography imaging in the
      management algorithm of hepatocellular carcinoma.
AB  - BACKGROUND AND AIM: (18) F-fluorodeoxyglucose (FDG)-positron emission tomography
      (PET) may detect primary lesions (PLs) and extrahepatic metastases (EHMs) only in
      advanced hepatocellular carcinoma (HCC) patients. We investigated the requirement
      of PET and the optimal timing of PET scanning for accurate staging and treatment
      planning. METHODS: We conducted a retrospective investigation of 64 HCC patients
      who underwent PET (median age, 74 years; male/female, 41/23; etiology, 46
      hepatitis C virus/4 hepatitis B virus/4 alcoholic/10 others). To determine the
      best timing for PET examinations, we analyzed PET result-based recommended
      treatment changes and characteristics of patients with FDG-avid PLs or EHMs.
      RESULTS: FDG-avid PLs were detected by PET in 22 patients (34%): 18 with
      hypervascular PL, 11 with serum alpha-fetoprotein levels >= 200 ng/mL, and 11
      beyond Milan criteria. EHMs were detected in 21 patients (33%: lymph nodes, 8;
      lung, 5; abdominal wall, 4; bone, 3; other organs, 4 [including overlapping]).
      Recommended treatments changed for 16 patients (25%) because of Barcelona Clinic
      Liver Cancer stage increases based on PET scanning. In multivariate analyses,
      serum alpha-fetoprotein levels >= 200 ng/mL and beyond Milan criteria were
      independent factors for FDG-avid PLs and a maximum standardized uptake value
      (SUVmax) of PLs of >= 4.0 was an independent factor for FDG-avid EHMs (P = 0.002,
      0.008, and 0.045, respectively). CONCLUSIONS: PET allows detection of HCC spread
      in patients with elevated serum alpha-fetoprotein levels or those beyond Milan
      criteria and detects EHMs in patients with PLs with high SUVmax values. Optimally
      timed PET scans can complement conventional imaging for accurate staging and
      treatment strategy determination.

PMID- 24730672
TI  - Pregnancy outcomes in multiple sclerosis patients previously treated with
      cyclophosphamide.
AB  - BACKGROUND: Cyclophosphamide (Cyc) can induce ovarian failure and can have
      teratogenic effect. Few case reports of successful pregnancies after Cyc
      treatment in women with autoimmune diseases and malignancies have been described.
      To date, there are no data about Cyc effect on pregnancy outcomes in MS patients.
      AIM OF THE STUDY: To describe pregnancy outcomes in multiple sclerosis (MS)
      patients treated with Cyc before conception. METHODS: We reviewed retrospectively
      the medical records of all MS patients who received Cyc from 1st of January 1997
      to 31st of March 2012, referring to the MS centre of the University of Catania.
      All pregnancies, occurred during the follow-up period after Cyc treatment, were
      recorded according to a computerized and standardized protocol (iMED). RESULTS:
      We found a total of 105 MS women of childbearing age; eleven patients experienced
      a pregnancy (10.4%); 10 of them had a successful delivery; and one experienced a
      voluntary abortion. Five women had a preterm delivery. One child was small for
      gestational age. CONCLUSIONS: Although the favourable pregnancy outcomes, Cyc
      should be avoided in young women planning a pregnancy. However, Cyc might be
      considered as a possible alternative to licensed therapies in few selected cases
      of very aggressive MS, including women of childbearing age.

PMID- 24730673
TI  - Event-related potentials reveal linguistic suppression effect but not enhancement
      effect on categorical perception of color.
AB  - The present study used the event-related potential technique to investigate the
      nature of linguistic effect on color perception. Four types of stimuli based on
      hue differences between a target color and a preceding color were used: zero hue
      step within-category color (0-WC); one hue step within-category color (1-WC); one
      hue step between-category color (1-BC); and two hue step between-category color
      (2-BC). The ERP results showed no significant effect of stimulus type in the 100
      200 ms time window. However, in the 200-350 ms time window, ERP responses to 1-WC
      target color overlapped with that to 0-WC target color for right visual field
      (RVF) but not left visual field (LVF) presentation. For the 1-BC condition, ERP
      amplitudes were comparable in the two visual fields, both being significantly
      different from the 0-WC condition. The 2-BC condition showed the same pattern as
      the 1-BC condition. These results suggest that the categorical perception of
      color in RVF is due to linguistic suppression on within-category color
      discrimination but not between-category color enhancement, and that the effect is
      independent of early perceptual processes.

PMID- 24730674
TI  - Comparisons of prognostic factors between young and elderly patients with chronic
      heart failure.
AB  - AIM: The purpose in the present study was to compare prognostic risk factors
      between older and younger chronic heart failure (CHF) patients. METHODS: We
      examined 598 consecutive CHF patients (476 men and 122 women, mean age 61.4 +/-
      14.3 years) who underwent cardiopulmonary exercise testing, echocardiography and
      blood examination. We divided the 598 patients into two groups: the elderly group
      (age >=75 years, n = 123) and the young group (age <75, n = 475). We compared
      blood testing data, exercise capacity, cardiac function and prognosis between the
      two groups. Patients were followed up (median 782 days) to register cardiac
      deaths or rehospitalization as a result of worsening heart failure. RESULTS:
      Patients in the elderly group were associated with higher frequencies of atrial
      fibrillation and diuretic use than those in the young group. Patients in the
      elderly group had lower hemoglobin concentration, more impaired renal function,
      higher plasma B-type natriuretic peptide (BNP) levels, smaller left ventricular
      volume, longer deceleration time of early mitral wave and lower exercise capacity
      than those in the young group. There were 199 cardiac events during follow-up
      periods. As expected, Kaplan-Meier analysis showed that patients in the elderly
      group had higher cardiac event rates than those in the young group. In the young
      group, multivariable Cox hazard analysis showed that hemoglobin concentration,
      log BNP and peak VO(2) were independent predictors related to cardiac events. In
      contrast, in the elderly group, estimated glomerular filtration rate, atrial
      fibrillation and peak VO(2) were independent factors to predict adverse clinical
      outcomes. CONCLUSIONS: Prognostic factors were different between the elderly and
      young patients in CHF.

PMID- 24730675
TI  - Periodic quantum chemical studies on anhydrous and hydrated acid clinoptilolite.
AB  - Periodic quantum chemistry methods as implemented in the crystal09 code were
      considered to study acid clinoptilolite (HEU framework type), both anhydrous and
      hydrated. The most probable location of acid sites and water molecules together
      with other structural details has been the object of particular attention.
      Calculations were performed at hybrid and pristine DFT levels of theory with a
      VDZP quality basis set in order to compare performances. It arises that PBE0
      provides the best agreement with experimental data as concerns structural
      features and the most stable Al distribution in the framework. The role of the
      water molecule distribution in the stability of the systems, the most probable
      structure that they induce in the material, and their eventual influence on
      further chemical modification processes, such as dealumination, are discussed in
      detail. Results show that, apart from the usually considered interactions of
      water molecules with the zeolite framework, that is, a H-bond with Bronsted acid
      sites and coordination with framework Al as Lewis ones, it is necessary to
      consider cooperation of other weaker effects so as to fully understand the
      hydration effect in this kind of materials.

PMID- 24730676
TI  - Efficacy of micafungin in pediatric immunocompromised patients with invasive
      fungal infection.
AB  - BACKGROUND: Micafungin, an antifungal echinocandin, has been indicated for
      pediatric patients with invasive fungal infection (IFI) in Japan and Europe. Its
      efficacy in immunocompromised pediatric patients with IFI, however, has not been
      fully investigated. METHODS: The safety and efficacy of micafungin as an
      antifungal therapy were analyzed in nine consecutive severe immunocompromised
      patients with IFI. RESULTS: Three patients with proven or probable Candida
      infections had complete response to micafungin therapy. Of the other six patients
      with proven, probable or possible Aspergillus infection, four had complete
      response and one had partial response to micafungin treatment. No severe adverse
      events were observed. CONCLUSIONS: In this small series, micafungin was effective
      for IFI caused by both Candida and Aspergillus species and no severe adverse
      events were observed in these immunocompromised patients.

PMID- 24730677
TI  - Assessing stabilization through pi-pi interactions in aromatic oligoamide beta
      sheet foldamers.
AB  - We have recently introduced aromatic oligoamide beta-sheet foldamers based on
      rigid turn units and short linear strands that undergo intramolecular pi-pi
      stacking (Sebaoun, L.; Maurizot, V.; Granier, T.; Kauffmann, B.; Huc, I. J. Am.
      Chem. Soc. 2014, 136, 2168). We now report that conformational stability in these
      structures can be reached using less rigid turn units and more extensive pi-pi
      interactions between longer linear strands. For this study, two-stranded sheets
      of variable length were prepared. Their conformation was assessed in solution by
      (1)H NMR and in the solid state by X-ray crystallography. 

PMID- 24730678
TI  - Homeless female U.S. veterans in a national supported housing program: comparison
      of individual characteristics and outcomes with male veterans.
AB  - As more women serve in the U.S. military, the proportion of females among
      homeless veterans is increasing. The current study compares the individual
      characteristics and 1-year outcomes of homeless female and male veterans in the
      Housing and Urban Development-Veterans Affairs Supportive Housing (HUD-VASH)
      program nationally. Administrative data on 43,853 veterans (10.69% females;
      89.31% males) referred to HUD-VASH were analyzed for gender differences at
      baseline and over a 1-year period. Homeless female veterans were younger, had
      shorter homeless and incarceration histories, and were less likely to have
      substance use disorders than men. However, despite being less likely to report
      combat exposure, female veterans were more likely to have posttraumatic stress
      disorder. Homeless female veterans were also much more likely to have dependent
      children with them and to plan to live with family members in supported housing.
      Once admitted to HUD-VASH, there were no gender differences in attrition or main
      housing outcomes. Case managers were faster to admit female veterans to the
      program, reported better working alliances, and provided more services related to
      employment and income than male veterans. These findings suggest homeless female
      veterans may have certain strengths, including being younger, less involved in
      the criminal justice system, and more adept at relating to professional and
      natural supports; but special attention to noncombat trauma and family-oriented
      services may be needed.

PMID- 24730680
TI  - Characterization of airborne particles generated from metal active gas welding
      process.
AB  - This study is focused on the characterization of particles emitted in the metal
      active gas welding of carbon steel using mixture of Ar + CO2, and intends to
      analyze which are the main process parameters that influence the emission itself.
      It was found that the amount of emitted particles (measured by particle number
      and alveolar deposited surface area) are clearly dependent on the distance to the
      welding front and also on the main welding parameters, namely the current
      intensity and heat input in the welding process. The emission of airborne fine
      particles seems to increase with the current intensity as fume-formation rate
      does. When comparing the tested gas mixtures, higher emissions are observed for
      more oxidant mixtures, that is, mixtures with higher CO2 content, which result in
      higher arc stability. These mixtures originate higher concentrations of fine
      particles (as measured by number of particles by cm(3) of air) and higher values
      of alveolar deposited surface area of particles, thus resulting in a more severe
      worker's exposure.

PMID- 24730681
TI  - Engine exhaust particulate and gas phase contributions to vascular toxicity.
AB  - Cardiovascular health effects of near-roadway pollution appear more substantial
      than other sources of air pollution. The underlying cause of this phenomenon may
      simply be concentration-related, but the possibility remains that gases and
      particulate matter (PM) may physically interact and further enhance systemic
      vascular toxicity. To test this, we utilized a common hypercholesterolemic mouse
      model (Apolipoprotein E-null) exposed to mixed vehicle emission (MVE; combined
      gasoline and diesel exhausts) for 6 h/d * 50 d, with additional permutations of
      removing PM by filtration and also removing gaseous species from PM by
      denudation. Several vascular bioassays, including matrix metalloproteinase-9
      protein, 3-nitrotyrosine and plasma-induced vasodilatory impairments, highlighted
      that the whole emissions, containing both particulate and gaseous components, was
      collectively more potent than MVE-derived PM or gas mixtures, alone. Thus, we
      conclude that inhalation of fresh whole emissions induce greater systemic
      vascular toxicity than either the particulate or gas phase alone. These findings
      lend credence to the hypothesis that the near-roadway environment may have a more
      focused public health impact due to gas-particle interactions.

PMID- 24730679
TI  - The therapeutic potential of cystathionine beta-synthetase/hydrogen sulfide
      inhibition in cancer.
AB  - SIGNIFICANCE: Cancer represents a major socioeconomic problem; there is a
      significant need for novel therapeutic approaches targeting tumor-specific
      pathways. RECENT ADVANCES: In colorectal and ovarian cancers, an increase in the
      intratumor production of hydrogen sulfide (H2S) from cystathionine beta-synthase
      (CBS) plays an important role in promoting the cellular bioenergetics,
      proliferation, and migration of cancer cells. It also stimulates peritumor
      angiogenesis inhibition or genetic silencing of CBS exerts antitumor effects both
      in vitro and in vivo, and potentiates the antitumor efficacy of anticancer
      therapeutics. CRITICAL ISSUES: Recently published studies are reviewed,
      implicating CBS overexpression and H2S overproduction in tumor cells as a tumor
      growth promoting "bioenergetic fuel" and "survival factor," followed by an
      overview of the experimental evidence demonstrating the anticancer effect of CBS
      inhibition. Next, the current state of the art of pharmacological CBS inhibitors
      is reviewed, with special reference to the complex pharmacological actions of
      aminooxyacetic acid. Finally, new experimental evidence is presented to reconcile
      a controversy in the literature regarding the effects of H2S donor on cancer cell
      proliferation and survival. FUTURE DIRECTIONS: From a basic science standpoint,
      future directions in the field include the delineation of the molecular mechanism
      of CBS up-regulation of cancer cells and the delineation of the interactions of
      H2S with other intracellular pathways of cancer cell metabolism and
      proliferation. From the translational science standpoint, future directions
      include the translation of the recently emerging roles of H2S in cancer into
      human diagnostic and therapeutic approaches.

PMID- 24730682
TI  - Neuroglobin mitigates mitochondrial impairments induced by acute inhalation of
      combustion smoke in the mouse brain.
AB  - CONTEXT: Acute inhalation of combustion smoke adversely affects brain homeostasis
      and energy metabolism. We previously showed that overexpressed neuroglobin (Ngb),
      neuron specific globin protein, attenuates the formation of smoke inhalation
      induced oxidative DNA damage, in vivo, in the mouse brain, while others reported
      protection by Ngb in diverse models of brain injury, mainly involving oxidative
      stress and hypoxic/ischemic insults. OBJECTIVE: To determine to what extent
      elevated Ngb ameliorates post smoke-inhalation brain bioenergetics and
      homeostasis in Ngb overexpressing transgenic mouse. METHODS: Smoke inhalation
      induced changes in bioenergetics were measured in the wild type and Ngb transgene
      mouse brain. Modulations of mitochondrial respiration were analyzed using the
      Seahorse XF24 flux analyzer and changes in cytoplasmic energy metabolism were
      assessed by measuring enzymatic activities and lactate in the course of post
      smoke recovery. RESULTS: Cortical mitochondria from Ngb transgene, better
      maintained ATP synthesis-linked oxygen consumption and unlike wild type
      mitochondria did not increase futile oxygen consumption feeding the proton leak,
      reflecting lesser smoke-induced mitochondrial compromise. Measurements revealed
      lesser reduction of mitochondrial ATP content and lesser compensatory increases
      in cytosolic energy metabolism, involving pyruvate kinase and lactate
      dehydrogenase activities as well as cytosolic lactate levels. Additionally,
      induction of c-Fos, the early response gene and key neuronal stress sensor, was
      attenuated in Ngb transgene compared to wild type brain after smoke. CONCLUSION:
      Considered together, these differences reflect lesser perturbations produced by
      acute inhalation of combustion smoke in the Ngb overexpressing mouse, suggesting
      that Ngb mitigates mitochondrial dysfunction and neurotoxicity and raises the
      threshold of smoke inhalation-induced brain injury.

PMID- 24730683
TI  - Synergistic assembly of heavy metal clusters and luminescent organic bridging
      ligands in metal-organic frameworks for highly efficient X-ray scintillation.
AB  - We have designed two metal-organic frameworks (MOFs) to efficiently convert X-ray
      to visible-light luminescence. The MOFs are constructed from M6(MU3-O)4(MU3
      OH)4(carboxylate)12 (M = Hf or Zr) secondary building units (SBUs) and anthracene
      based dicarboxylate bridging ligands. The high atomic number of Zr and Hf in the
      SBUs serves as effective X-ray antenna by absorbing X-ray photons and converting
      them to fast electrons through the photoelectric effect. The generated electrons
      then excite multiple anthracene-based emitters in the MOF through inelastic
      scattering, leading to efficient generation of detectable photons in the visible
      spectrum. The MOF materials thus serve as efficient X-ray scintillators via
      synergistic X-ray absorption by the metal-cluster SBUs and optical emission by
      the bridging ligands. 

PMID- 24730684
TI  - Antibiotic prescription patterns among Swedish dentists working with dental
      implant surgery: adherence to recommendations.
AB  - OBJECTIVES: To investigate antibiotic prophylaxis prescription behaviors among
      Swedish dentists working with dental implant surgery and the influence of
      scientific reviews. MATERIAL AND METHODS: An observational questionnaire study
      was conducted in 2008 and 2012. Dental clinic addresses were found through online
      search services of Swedish telephone directories. The questionnaires were posted
      to eligible dentists (120 in 2008, 161 in 2012) in the Stockholm region, Sweden.
      Absolute frequencies were used to describe the data. Chi-square tests were
      applied to assess statistically significant differences. RESULTS: The response
      rate was 75% in 2008 and 88% in 2012. In 2008, 88% of the dentists routinely
      prescribed antibiotic prophylaxis when performing implant surgery and 74% in 2012
      (P = 0.01). There was a significant reduction in the dentists prescription
      patterns as 65% prescribed a single dose in 2012, compared to 49% in 2008 (P =
      0.04). Amoxicillin was the drug of choice for 47% of the respondents in 2012, and
      21% in 2008 (P = 0.01). Dentists without postgraduate clinical training were
      significantly more prone to extend antibiotic administration after surgery (P <
      0.009). CONCLUSIONS: There is a wide variation in the choice of compound and
      prescription patterns of prophylactic antibiotic prior to implant insertion. A
      reduction in antibiotic prescription to a single dose was observed comparing 2008
      and 2012, probably influenced by scientific reviews. Dentists with postgraduate
      education are more likely to limit antibiotic usage.

PMID- 24730685
TI  - Mobility improvement and temperature dependence in MoSe2 field-effect transistors
      on parylene-C substrate.
AB  - We report low-temperature scanning tunneling microscopy characterization of MoSe2
      crystals and the fabrication and electrical characterization of MoSe2 field
      effect transistors on both SiO2 and parylene-C substrates. We find that the
      multilayer MoSe2 devices on parylene-C show a room-temperature mobility close to
      the mobility of bulk MoSe2 (100-160 cm(2) V(-1) s(-1)), which is significantly
      higher than that on SiO2 substrates (~50 cm(2) V(-1) s(-1)). The room-temperature
      mobility on both types of substrates are nearly thickness-independent. Our
      variable-temperature transport measurements reveal a metal-insulator transition
      at a characteristic conductivity of e(2)/h. The mobility of MoSe2 devices
      extracted from the metallic region on both SiO2 and parylene-C increases up to
      ~500 cm(2) V(-1) s(-1) as the temperature decreases to ~100 K, with the mobility
      of MoSe2 on SiO2 increasing more rapidly. In spite of the notable variation of
      charged impurities as indicated by the strongly sample-dependent low-temperature
      mobility, the mobility of all MoSe2 devices on SiO2 converges above 200 K,
      indicating that the high temperature (>200 K) mobility in these devices is nearly
      independent of the charged impurities. Our atomic force microscopy study of SiO2
      and parylene-C substrates further rules out the surface roughness scattering as a
      major cause of the substrate-dependent mobility. We attribute the observed
      substrate dependence of MoSe2 mobility primarily to the surface polar optical
      phonon scattering originating from the SiO2 substrate, which is nearly absent in
      MoSe2 devices on parylene-C substrate. 

PMID- 24730686
TI  - Concerns about the Joint National Committee on Prevention, Detection, Evaluation,
      and Treatment of High Blood Pressure 8 blood pressure panel member
      recommendations and their relevance to metabolic syndrome.

PMID- 24730687
TI  - Response of the seated human body to whole-body vertical vibration: biodynamic
      responses to sinusoidal and random vibration.
AB  - The dependence of biodynamic responses of the seated human body on the frequency,
      magnitude and waveform of vertical vibration has been studied in 20 males and 20
      females. With sinusoidal vibration (13 frequencies from 1 to 16 Hz) at five
      magnitudes (0.1-1.6 ms(-2) r.m.s.) and with random vibration (1-16 Hz) at the
      same magnitudes, the apparent mass of the body was similar with random and
      sinusoidal vibration of the same overall magnitude. With increasing magnitude of
      vibration, the stiffness and damping of a model fitted to the apparent mass
      reduced and the resonance frequency decreased (from 6.5 to 4.5 Hz). Male and
      female subjects had similar apparent mass (after adjusting for subject weight)
      and a similar principal resonance frequency with both random and sinusoidal
      vibration. The change in biodynamic response with increasing vibration magnitude
      depends on the frequency of the vibration excitation, but is similar with
      sinusoidal and random excitation.

PMID- 24730688
TI  - Primary health care service use among women who have recently left an abusive
      partner: income and racialization, unmet need, fits of services, and health.
AB  - Primary health care (PHC) can improve the health of women who have experienced
      intimate partner violence; yet, access to and fit of PHC services may be shaped
      by income and racialization. We examined whether income and racialization were
      associated with differences in PHC service use, unmet needs, fit with needs, and
      mental and physical health in a sample of 286 women who had separated from an
      abusive partner. Mothers, unemployed women, and those with lower incomes used
      more PHC services and reported a poorer fit of services. Poorer fit of services
      was related to poorer mental and physical health. 

PMID- 24730689
TI  - Biogeochemical processes governing natural pyrite oxidation and release of acid
      metalliferous drainage.
AB  - The oxidative dissolution of sulfide minerals (principally pyrite) is responsible
      for the majority of acid metalliferous drainage from mine sites, which represents
      a significant environmental problem worldwide. Understanding the complex
      biogeochemical processes governing natural pyrite oxidation is critical not only
      for solving this problem but also for understanding the industrial bioleaching of
      sulfide minerals. To this end, we conducted a simulated experiment of natural
      pyrite oxidative dissolution. Pyrosequencing analysis of the microbial community
      revealed a distinct succession across three stages. At the early stage, a newly
      proposed genus, Tumebacillus (which can use sodium thiosulfate and sulfite as the
      sole electron donors), dominated the microbial community. At the midstage,
      Alicyclobacillus (the fifth most abundant genus at the early stage) became the
      most dominant genus, whereas Tumebacillus was still ranked as the second most
      abundant. At the final stage, the microbial community was dominated by
      Ferroplasma (the tenth most abundant genus at the early stage). Our geochemical
      and mineralogical analyses indicated that exchangeable heavy metals increased as
      the oxidation progressed and that some secondary sulfate minerals (including
      jarosite and magnesiocopiapite) were formed at the final stage of the oxidation
      sequence. Additionally, we propose a comprehensive model of biogeochemical
      processes governing the oxidation of sulfide minerals. 

PMID- 24730691
TI  - Robot-assisted gastrectomy and oesophagectomy for cancer.
AB  - BACKGROUND: Robot-assisted surgery is a technically feasible alternative to open
      and laparoscopic surgery, which is being more frequently used in general surgery.
      We undertook this review to investigate whether robotic assistance provides a
      significant benefit for oesophagogastric cancer surgery. METHODS: Electronic
      databases were searched for original English-language publications for robotic
      assisted gastrectomy and oesophagectomy between January 1990 and October 2013.
      RESULTS: Sixty-one publications were included. Thirty-five included gastrectomy,
      31 included oesophagectomy and five included both operations. Several
      publications suggest that robot-assisted subtotal gastrectomy can be as safe and
      effective as an open or laparoscopic procedure, with equal outcomes with regard
      to the number of lymph nodes resected, overall morbidity and perioperative
      mortality, and length of hospital stay. Robotic assistance is associated with
      longer operation times but also with less blood loss in some reports. A
      significant benefit for robotic assistance has not been shown for the more
      extensive operations of oesophagectomy or total gastrectomy with D2
      lymphadenectomy. There are very few oncologic data regarding local recurrence or
      long-term survival for any of the robotic operations. CONCLUSIONS: No significant
      differences in morbidity, mortality or number of lymph node harvested have been
      shown between robot-assisted and laparoscopic gastrectomy or oesophagectomy.
      Robotic surgery, with its relatively short learning curve, may facilitate
      reproducible minimally invasive surgery in this field but operation times are
      reportedly longer and cost differences remain unclear. Randomized trials with
      oncologic outcomes and cost comparisons are needed.

PMID- 24730690
TI  - ILAE official report: a practical clinical definition of epilepsy.
AB  - Epilepsy was defined conceptually in 2005 as a disorder of the brain
      characterized by an enduring predisposition to generate epileptic seizures. This
      definition is usually practically applied as having two unprovoked seizures >24 h
      apart. The International League Against Epilepsy (ILAE) accepted recommendations
      of a task force altering the practical definition for special circumstances that
      do not meet the two unprovoked seizures criteria. The task force proposed that
      epilepsy be considered to be a disease of the brain defined by any of the
      following conditions: (1) At least two unprovoked (or reflex) seizures occurring
      >24 h apart; (2) one unprovoked (or reflex) seizure and a probability of further
      seizures similar to the general recurrence risk (at least 60%) after two
      unprovoked seizures, occurring over the next 10 years; (3) diagnosis of an
      epilepsy syndrome. Epilepsy is considered to be resolved for individuals who
      either had an age-dependent epilepsy syndrome but are now past the applicable age
      or who have remained seizure-free for the last 10 years and off antiseizure
      medicines for at least the last 5 years. "Resolved" is not necessarily identical
      to the conventional view of "remission or "cure." Different practical definitions
      may be formed and used for various specific purposes. This revised definition of
      epilepsy brings the term in concordance with common use. A PowerPoint slide
      summarizing this article is available for download in the Supporting Information
      section here. 

PMID- 24730692
TI  - Catalytic enantioselective 1,3-dipolar cycloadditions of azomethine ylides for
      biology-oriented synthesis.
AB  - Cycloaddition reactions are among the most powerful methods for the synthesis of
      complex compounds. In particular, the development and application of the 1,3
      dipolar cycloaddition, an important member of this reaction class, has grown
      immensely due to its powerful ability to efficiently build various five-membered
      heterocycles. Azomethine ylides are commonly used as dipoles for the synthesis of
      the pyrrolidine scaffold, which is an important motif in natural products,
      pharmaceuticals, and biological probes. The reaction between azomethine ylides
      and cyclic dipolarophiles allows access to polycyclic products with considerable
      complexity. The extensive application of the 1,3-dipolar cycloaddition is based
      on the fact that the desired products can be obtained with high yield in a regio-
      and stereocontrolled manner. The most attractive feature of the 1,3-dipolar
      cycloaddition of azomethine ylides is the possibility to generate pyrrolidines
      with multiple stereocenters in a single step. The development of enantioselective
      cycloadditions became a subject of intensive and impressive studies in recent
      years. Among many modes of stereoinduction, the application of chiral metal
      ligand complexes has emerged as the most viable option for control of
      enantioselectivity. In chemical biology research based on the principle of
      biology-oriented synthesis (BIOS), compound collections are prepared inspired by
      natural product scaffolds. In BIOS, biological relevance is employed as the key
      criterion to generate hypotheses for the design and synthesis of focused compound
      libraries. In particular, the underlying scaffolds of natural product classes
      provide inspiration for BIOS because they define the areas of chemical space
      explored by nature, and therefore, they can be regarded as "privileged". The
      scaffolds of natural products are frequently complex and rich in stereocenters,
      which necessitates the development of efficient enantioselective methodologies.
      This Account highlights examples, mostly from our work, of the application of 1,3
      dipolar cycloaddition reactions of azomethine ylides for the catalytic
      enantioselective synthesis of complex products. We successfully applied the 1,3
      dipolar cycloaddition in the synthesis of spiro-compounds such as spirooxindoles,
      for kinetic resolution of racemic compounds in the synthesis of an iridoid
      inspired compound collection and in the synthesis of a nitrogen-bridged bicyclic
      tropane scaffold by application of 1,3-fused azomethine ylides. Furthermore, we
      performed the synthesis of complex molecules with eight stereocenters using
      tandem cycloadditions. In a programmable sequential double cycloaddition, we
      demonstrated the synthesis of both enantiomers of complex products by simple
      changes in the order of addition of chemicals. Complex products were obtained
      using enantioselective higher order [6 + 3] cycloaddition of azomethine ylides
      with fulvenes followed by Diels-Alder reaction. The bioactivity of these compound
      collections is also discussed.

PMID- 24730693
TI  - The scare tactic: do fear appeals predict motivation and exam scores?
AB  - Prior to high-stakes exams, teachers use persuasive messages that highlight to
      students the possible consequences of failure. Such messages are known as fear
      appeals. This study examined whether fear appeals relate to self- and non-self
      determined motivation and academic performance. Data were collected in 3 waves.
      Self-report data pertaining to perceived fear appeals were collected in the first
      wave, self-report data pertaining to self-determined motivation were collected in
      the second wave, and exam scores were collected in the third wave. An increased
      frequency of fear appeals and the appraisal of fear appeals as threatening
      predicted lower self-determined motivation but were largely unrelated to non-self
      determined motivation. An increased frequency of fear appeals and the appraisal
      of fear appeals as threatening predicted lower examination performance that was
      partly mediated by lower self-determined motivation. These findings support a
      position derived from self-worth theory that the negative consequences of fear
      appeals arise from their focus on avoiding failure rather than their focus on
      extrinsic consequences. We suggest that teachers and instructors need to be aware
      how seemingly motivational statements can unwittingly promote lower self
      determined motivation.

PMID- 24730694
TI  - A facile Fmoc solid phase synthesis strategy to access epimerization-prone
      biosynthetic intermediates of glycopeptide antibiotics.
AB  - A rapid protocol based on Fmoc-chemistry for the solid phase peptide synthesis of
      vancomycin- and teicoplanin-type peptides is described. Epimerization of highly
      racemization-prone arlyglycine derivatives is suppressed through optimized Fmoc
      deprotection and coupling conditions. Starting from easily accessible Fmoc
      protected amino acids, this strategy enables the enantioselective synthesis of
      peptides corresponding to intermediates found in vancomycin and teicoplanin
      biosynthesis with excellent purity and in high yields (38%-71%). 

PMID- 24730695
TI  - Comparison of different commercial serological tests for the detection of
      Toxoplasma gondii antibodies in serum of naturally exposed pigs.
AB  - Toxoplasma gondii is the aetiological agent of the zoonotic disease toxoplasmosis
      and transmitted among other ways by chemically and physically untreated, that is,
      raw pork to humans. The detection of Toxoplasma gondii is impossible by currently
      practiced meat inspection, but serological tests can be used to detect Toxoplasma
      gondii antibodies in pig herds and can consequently be helpful to identify
      potentially contaminated pork. Therefore, appropriate serological tests are
      required. In this study, serum samples of 1368 naturally exposed slaughter pigs
      from 73 Austrian farms were collected. Serum samples of at least 16 slaughter
      pigs per farm were tested. The prevalence of Toxoplasma gondii antibodies in
      serum was measured by a commercial available modified agglutination test (MAT)
      and compared to three different commercial available enzyme-linked immunosorbent
      assays (ELISA). The MAT detected 6.5%, ELISA I 6.7%, ELISA II 4.8% and ELISA III
      4.3% of the pigs as Toxoplasma gondii antibody positive. The agreement, according
      to the kappa coefficient (kappa), was substantial between the MAT and ELISA I
      (kappa = 0.62), II (kappa = 0.64) and III (kappa = 0.67). A better agreement was
      determined between ELISA I and II (kappa = 0.715), ELISA I and III (kappa =
      0.747) and ELISA II and III (kappa = 0.865). At least one pig per farm was
      detected Toxoplasma gondii antibody positive in 17 (23.3%) farms by the MAT, 26
      (35.6%) farms by ELISA I, 16 (21.9%) farms by ELISA II and 11 (15.1%) farms by
      ELISA III. Pig farms with a high number of Toxoplasma gondii antibody-positive
      pigs or high antibody titres were identified by all of the four used serological
      tests. Concerning the occurrence of Toxoplasma gondii antibodies in Austrian pig
      farms, a monitoring and surveillance programme would be reasonable to find high
      risk farms.

PMID- 24730696
TI  - Event familiarity influences memory detection using the aIAT.
AB  - The developers of the autobiographical Implicit Association Test (aIAT) describe
      it as a possible memory detection tool. This claim rests on the assumption the
      aIAT can reliably and automatically detect the accuracy of autobiographical
      events. However, the aIAT may be susceptible to factors that affect the
      assessment of truth vs. falseness, such as the relative familiarity of those
      events. We compared aIAT performance when participants reported recent vs.
      childhood autobiographical events, and when participants imagined vs. did not
      imagine a fabricated autobiographical event. The aIAT was less effective at
      distinguishing between real and fabricated events from childhood, compared to
      recent real and fabricated events. Imagining a fabricated event did not affect
      aIAT performance; however, there was a trend in the data suggesting imagination
      may have reduced the effect of event recency. Our results provide further
      evidence that reducing or enhancing source confusion-via familiarity-can
      influence the predictive value of the aIAT. 

PMID- 24730697
TI  - Effect of beta-blockers on platelet aggregation: a systematic review and meta
      analysis.
AB  - AIMS: Platelets play an important role in cardiovascular disease, and beta
      blockers are often prescribed for cardiovascular disease prevention. beta
      Blockers may directly affect platelet aggregation, because beta-adrenergic
      receptors are present on platelets. There is uncertainty about the existence and
      magnitude of an effect of beta-blockers on platelet aggregation. The aim of this
      study was to perform a systematic review and meta-analysis of the effect of beta
      blockers on platelet aggregation. METHODS: MEDLINE and EMBASE were searched until
      April 2014. Two reviewers independently performed data extraction and risk of
      bias assessment. Type of beta-blocker, population, treatment duration and
      platelet aggregation were extracted. Standardized mean differences were
      calculated for each study and pooled in a random-effects meta-analysis. RESULTS:
      We retrieved 31 studies (28 clinical trials and three observational studies).
      beta-Blockers decreased platelet aggregation (standardized mean difference -0.54,
      95% confidence interval -0.85 to -0.24, P < 0.0001). This corresponds to a
      reduction of 13% (95% confidence interval 8-17%). Nonselective lipophilic beta
      blockers decreased platelet aggregation more than selective nonlipophilic beta
      blockers. CONCLUSIONS: Clinically used beta-blockers significantly reduce
      platelet aggregation. Nonselective lipophilic beta-blockers seem to reduce
      platelet aggregation more effectively than selective nonlipophilic beta-blockers.
      These findings may help to explain why some beta-blockers are more effective than
      others in preventing cardiovascular disease.

PMID- 24730698
TI  - New fatty acids from the Red Sea sponge Mycale euplectellioides.
AB  - Chemical investigation of the Red Sea sponge Mycale euplectellioides afforded two
      new compounds; hexacosa-(6Z,10Z)-dienoic acid methyl ester (1) and hexacosa
      (6Z,10Z)-dienoic acid (2), along with two known compounds: icosa-(8Z,11Z)-dienoic
      acid methyl ester (3) and beta-sitosterol (4). The structures were elucidated by
      the interpretation of their spectral data. The total methanol extract (TME) of
      the sponge exhibited potent antimicrobial activity against the different strains
      at a concentration of 100 mg/mL. All tested fractions did not exhibit any
      activity against Serratia marcescens and tested fungal strains. The TME and
      different fractions displayed anti-inflammatory and antipyretic activities at
      doses of 100 and 200 mg/kg compared with indomethacin (8 mg). The TME exhibited a
      remarkable hepato-protective effect in CCl4-induced liver damage compared with
      silymarin. Furthermore, compounds 1 and 2 displayed weak activity against A549
      non-small cell lung cancer, the U373 glioblastoma and the PC-3 prostate cancer
      cell lines. 

PMID- 24730699
TI  - Hydration of the sulfuric acid-methylamine complex and implications for aerosol
      formation.
AB  - The binary H2SO4-H2O nucleation is one of the most important pathways by which
      aerosols form in the atmosphere, and the presence of ternary species like amines
      increases aerosol formation rates. In this study, we focus on the hydration of a
      ternary system of sulfuric acid (H2SO4), methylamine (NH2CH3), and up to six
      waters to evaluate its implications for aerosol formation. By combining molecular
      dynamics (MD) sampling with high-level ab initio calculations, we determine the
      thermodynamics of forming H2SO4(NH2CH3)(H2O)n, where n = 0-6. Because it is a
      strong acid-base system, H2SO4-NH2CH3 quickly forms a tightly bound HSO4(-)
      NH3CH3(+) complex that condenses water more readily than H2SO4 alone. The
      electronic binding energy of H2SO4-NH2CH3 is -21.8 kcal mol(-1) compared with 
      16.8 kcal mol(-1) for H2SO4-NH3 and -12.8 kcal mol(-1) for H2SO4-H2O. Adding one
      to two water molecules to the H2SO4-NH2CH3 complex is more favorable than adding
      to H2SO4 alone, yet there is no systematic difference for n >= 3. However, the
      average number of water molecules around H2SO4-NH2CH3 is consistently higher than
      that of H2SO4, and it is fairly independent of temperature and relative humidity.

PMID- 24730700
TI  - NADPH oxidases: progress and opportunities.
AB  - From the initial discovery in 1999 that NADPH oxidases comprise a family of
      enzymes to our current focus on drug development to treat multiple pathologies
      related to this enzyme family, progress has been swift and impressive. We have
      expanded our understanding of the extent of the family, the basic enzymatic
      biochemistry, the multiple cellular functions controlled by NADPH oxidases, and
      their varied roles in physiology and diseases. We have developed numerous cell
      culture tools, animal models, and human databases that have allowed us to delve
      deeply into the various roles of these enzymes. However, it is clear that much
      remains to be learned and that there are many opportunities for new tools and new
      research directions to more fully understand these critical enzymes. With this
      Antioxidants and Redox Signaling Forum, we explore in detail the progress,
      challenges, and opportunities in Nox biology. Progress so far has clearly shown
      that NADPH oxidases are integral to fully functioning organisms and that the
      dysregulation of Nox enzymes contributes to a wide variety of pathologies. We
      have the opportunity to develop new tools and small molecules that will not only
      help us to better understand the molecular underpinnings of NADPH oxidases but
      also to develop treatments for diverse human diseases.

PMID- 24730701
TI  - Branchio-oto-renal syndrome: comprehensive review based on nationwide
      surveillance in Japan.
AB  - Branchio-oto-renal (BOR) syndrome is an autosomal dominant disorder characterized
      by branchiogenic malformation, hearing loss and renal anomalies. The prevalence
      of BOR syndrome is 1/40,000 in Western countries, and nationwide surveillance in
      2009-2010 identified approximately 250 BOR patients in Japan. Three causative
      genes for BOR syndrome have been reported thus far: EYA1, SIX1, and SIX5, but the
      causative genes for approximately half of all BOR patients remain unknown. This
      review article discusses the epidemiology, clinical symptoms, genetic background
      and management of BOR syndrome.

PMID- 24730702
TI  - Oral antiviral therapy improves the diagnostic accuracy of alpha-fetoprotein
      levels in patients with chronic hepatitis B.
AB  - BACKGROUND AND AIMS: Analysis of alpha-fetoprotein (AFP) levels affords limited
      diagnostic accuracy because of the high false-positive rates, especially in those
      with active chronic hepatitis B (CHB). We measured AFP levels before and after
      commencement of oral antiviral therapy and explored the utility of these data in
      terms of early detection of hepatocellular carcinoma (HCC) in patients with CHB.
      METHODS: A total of 207 patients with CHB who were treated with an oral antiviral
      agent were consecutively included. Dynamic changes in AFP levels and the
      diagnostic utility of such changes for HCC detection during the therapy were
      explored. RESULTS: The proportions of patients showing elevated AFP levels (>= 20
      ng/mL) were 22.2%, 5.5%, and 1.3% at baseline; and at 6 and 12 months after
      commencement of antiviral therapy, respectively. All patients who did not suffer
      from HCC exhibited normalization of AFP levels at 12 months. The cumulative
      incidence of HCC was 9.5% during 36 months of follow-up. If AFP levels were over
      20 ng/mL after 12 months of antiviral treatment, the probability of HCC
      development approached certainty. The positive predictive value for HCC
      development remained at 100% in patients prescribed long-term (>= 12 months)
      antiviral therapy, if AFP levels persistently or abruptly elevated more than 12
      ng/mL. CONCLUSIONS: In the era of oral antiviral agents, AFP might be a useful
      biomarker for HCC surveillance in patients with CHB.

PMID- 24730703
TI  - Quality and safety of red blood cells stored in two additive solutions subjected
      to multiple room temperature exposures.
AB  - BACKGROUND AND OBJECTIVES: Many international standards state that red blood cell
      (RBC) products should be discarded if left out of controlled temperature storage
      for longer than 30 min to reduce the risk of bacterial growth and RBC loss of
      viability. This study aimed to verify whether repeated short-time exposures to
      room temperature (RT) influence RBCs quality and bacterial proliferation.
      MATERIALS AND METHODS: Saline-adenine-glucose-mannitol (SAGM) and AS-3 RBC units
      were split and exposed to RT for 30 or 60 min on day 2, 7, 14, 21, and 42 of
      storage while reference units remained stored at 1-6 degrees C. Red blood cell in
      vitro quality parameters were evaluated after each exposure. In a second
      experiment, SAGM and AS-3 RBC units were split and inoculated with Staphylococcus
      epidermidis (5 CFU/ml), Serratia marcescens (1 CFU/ml), and Serratia liquefaciens
      (1 CFU/ml). Reference units remained in storage while test units were exposed as
      described previously. Bacterial concentrations were investigated after each
      exposure. RESULTS: No differences were noticed between reference and test units
      in any of the in vitro parameters investigated. S. epidermidis did not grow in
      either reference or exposed RBCs. While S. marcescens did not grow in AS-3,
      bacterial growth was observed in RT-exposed SAGM RBCs on day 42. Similar growth
      was obtained for S. liquefaciens in the two additive solutions for both reference
      and test units. CONCLUSION: Short-time exposures to RT do not affect RBC quality
      and do not significantly influence bacterial growth. An expansion of the '30
      minute' rule to 60 min should be considered by regulatory agencies.

PMID- 24730704
TI  - Self-assembled nanostructured photoanodes with staggered bandgap for efficient
      solar energy conversion.
AB  - Vertically oriented Ta-W-O nanotube array films were fabricated via the
      anodization of Ta-W alloy foils in HF-containing electrolytes. HF concentration
      is a key parameter in achieving well-adhered nanotube array structure. X-ray
      photoelectron spectroscopy (XPS) and diffuse reflectance measurements confirm the
      staggered band-alignment between Ta2O5 and WO3, which facilitates the separation
      of charge carriers. The nanotubes made of Ta-W films containing 10% W showed 100
      fold improvement in the measured photocurrent compared to pristine Ta2O5 upon
      their use to split water photoelectrochemically. This enhancement was related to
      the efficient charge transport and the red shift in absorption spectrum with
      increase of the W content, which was asserted by ultrafast transient absorption
      (TA) spectroscopy measurements. The TA measurements showed the elimination of
      trap states upon annealing Ta-W-O nanotubes and, hence, minimizing the charge
      carrier trapping, whereas the trap states remain in pristine Ta2O5 nanotubes even
      after annealing. 

PMID- 24730705
TI  - Two-dimensional water diffusion at a graphene-silica interface.
AB  - Because of the dominant role of the surface of molecules and their individuality,
      molecules behave distinctively in a confined space, which has far-reaching
      implications in many physical, chemical, and biological systems. Here we
      demonstrate that graphene forms a unique atom-thick interstitial space that
      enables the study of molecular diffusion in two dimensions with underlying silica
      substrates. Raman spectroscopy visualized intercalation of water from the edge to
      the center underneath graphene in real time, which was dictated by the
      hydrophilicity of the substrates. In addition, graphene undergoes reversible
      deformation to conform to intercalating water clusters or islands. Atomic force
      microscopy confirmed that the interfacial water layer is only ca. 3.5 A thick,
      corresponding to one bilayer unit of normal ice. This study also demonstrates
      that oxygen species responsible for the ubiquitous hole doping are located below
      graphene. In addition to serving as a transparent confining wall, graphene and
      possibly other two-dimensional materials can be used as an optical indicator
      sensitive to interfacial mass transport and charge transfer. 

PMID- 24730706
TI  - Effects of respirator ambient air cooling on thermophysiological responses and
      comfort sensations.
AB  - This investigation assessed the thermophysiological and subjective impacts of
      different respirator ambient air cooling options while wearing chemical and
      biological personal protective equipment in a warm environment (32.7 +/- 0.4
      degrees C, 49.6 +/- 6.5% RH). Ten volunteers participated in 90-min heat exposure
      trials with and without respirator (Control) wear and performed computer
      generated tasks while seated. Ambient air cooling was provided to respirators
      modified to blow air to the forehead (FHC) or to the forehead and the breathing
      zone (BZC) of a full-facepiece air-purifying respirator using a low-flow (45
      L.min(-1)) mini-blower. An unmodified respirator (APR) trial was also completed.
      The highest body temperatures (TTY) and least favorable comfort ratings were
      observed for the APR condition. With ambient cooling over the last 60 min of heat
      exposure, TTY averaged 37.4 +/- 0.6 degrees C for Control, 38.0 +/- 0.4 degrees C
      for APR, 37.8 +/- 0.5 degrees C for FHC, and 37.6 +/- 0.7 degrees C for BZC
      conditions independent of time. Both the FHC and BZC ambient air cooling
      conditions reduced facial skin temperatures, reduced the rise in body
      temperatures, and led to more favorable subjective comfort and thermal sensation
      ratings over time compared to the APR condition; however statistical differences
      among conditions were inconsistent. Independent of exposure time, average
      breathing apparatus comfort scores with BZC (7.2 +/- 2.5) were significantly
      different from both Control (8.9 +/- 1.4) and APR (6.5 +/- 2.2) conditions when
      ambient cooling was activated. These findings suggest that low-flow ambient air
      cooling of the face under low work rate conditions and mild hyperthermia may be a
      practical method to minimize the thermophysiological strain and reduce perceived
      respirator discomfort.

PMID- 24730708
TI  - Effect of propranolol on facial scanning in autism spectrum disorder: a
      preliminary investigation.
AB  - BACKGROUND: Autism spectrum disorder (ASD) is a neurodevelopmental disorder
      characterized by social communication impairments and restricted, repetitive
      behaviors. Whereas current pharmacological interventions for ASD focus primarily
      on psychiatric symptoms, including agitation and obsessive behaviors, few agents
      target core symptomatology. It has been previously hypothesized that
      abnormalities in facial scanning, such as reduced eye contact or increased mouth
      fixation, contribute to social communication deficits in ASD. In addition,
      previous reports have suggested elevated stress and anxiety in ASD, symptoms that
      are believed to impact facial scanning patterns. OBJECTIVES: The present pilot
      study sought to explore the effects of pharmacological intervention via
      propranolol, a nonselective beta-adrenergic antagonist and known anxiolytic, on
      facial scanning in ASD. Specifically, we wished to determine whether there is an
      increase in eye contact and a decrease in mouth fixation with administration of
      propranolol. METHOD: A sample of 14 participants with ASD and 14 matched controls
      participated in two study sessions in which propranolol and placebo were
      administered in a counterbalanced, double-blinded manner. At each session, ocular
      fixation data were collected during presentation of video stimuli of 16 human
      faces. Fixation time on the eye, nose, and mouth regions of the face stimuli was
      analyzed. RESULTS: The baseline fixation patterns for the ASD and control groups
      did not significantly differ; however, administration of propranolol was
      associated with a significant reduction in mouth fixation for the ASD group.
      Additionally, mouth fixation was positively related to nonverbal communication
      impairment in the ASD group. CONCLUSIONS: Although eye fixation in ASD appears
      typical in the present study, the effect of propranolol in reducing mouth
      fixation suggests an important focus for further research. Future studies are
      needed to better characterize the relationship between stress and anxiety and
      facial scanning in ASD, as well as the effects of pharmacological intervention.

PMID- 24730709
TI  - Early loading of 6-mm-short implants with a moderately rough surface supporting
      single crowns--a prospective 5-year cohort study.
AB  - AIM: To evaluate prospectively the clinical and radiographic outcomes after 5
      years of early loading of 6-mm implants with a moderately rough (SLActive((r)) )
      surface supporting single crowns in the posterior regions. MATERIAL AND METHODS:
      Thirty-five consecutive patients received 40 SLActive((r)) (Straumann) 6-mm
      implants with a diameter of 4.1 mm (n = 19) or 4.8 mm (n = 21). Insertion torque
      and resonance frequency analysis (RFA) were measured at implant installation. RFA
      was also measured at abutment connection. SynOcta abutments were tightened with
      35 Ncm after 6 weeks of healing, and single porcelain fuse to metal crowns was
      cemented within 1 week. Implant survival rate and marginal bone loss were
      evaluated at various time intervals until 5 years after loading. The clinical
      crown/implant ratio was calculated as well. RESULTS: Two of 40 implants were lost
      before loading (incorporation rate 95%), and no further implant loss or technical
      complications were encountered during the 5-year follow-up period. A mean
      marginal bone loss of 0.7 +/- 0.6 mm was found after 5 years of function. The
      clinical crown/implant ratio increased with time from 1.6 at the delivery of the
      prosthesis to 2 after 5 years of loading. CONCLUSION: Six millimeter implants
      with a SLActive((r)) moderately rough surface supporting single crowns in the
      posterior region and loaded after 6-7 weeks maintained full function for at least
      5 year with low marginal bone resorption.

PMID- 24730710
TI  - Response of the seated human body to whole-body vertical vibration: discomfort
      caused by sinusoidal vibration.
AB  - Frequency weightings for predicting vibration discomfort assume the same
      frequency-dependence at all magnitudes of vibration, whereas biodynamic studies
      show that the frequency-dependence of the human body depends on the magnitude of
      vibration. This study investigated how the frequency-dependence of vibration
      discomfort depends on the acceleration and the force at the subject-seat
      interface. Using magnitude estimation, 20 males and 20 females judged their
      discomfort caused by sinusoidal vertical acceleration at 13 frequencies (1-16 Hz)
      at magnitudes from 0.1 to 4.0 ms(-2) r.m.s. The frequency-dependence of their
      equivalent comfort contours depended on the magnitude of vibration, but was less
      dependent on the magnitude of dynamic force than the magnitude of acceleration,
      consistent with the biodynamic non-linearity of the body causing some of the
      magnitude-dependence of equivalent comfort contours. There were significant
      associations between the biodynamic responses and subjective responses at all
      frequencies in the range 1-16 Hz. Practitioner Summary: Vertical seat vibration
      causes discomfort in many forms of transport. This study provides the frequency
      dependence of vibration discomfort over a range of vibration magnitudes and shows
      how the frequency weightings in the current standards can be improved.

PMID- 24730711
TI  - Reliability and validity of the Chinese version of the Children's Fear Survey
      Schedule-Dental Subscale.
AB  - BACKGROUND: The Children's Fear Survey Schedule-Dental Subscale (CFSS-DS) is a
      commonly used questionnaire that measures children's dental fears. AIM: This
      study aimed to examine the reliability and validity of the Chinese version of the
      CFSS-DS. DESIGN: The CFSS-DS was translated into Chinese and administered to
      children in a dental office. The sample comprised 206 child patients aged 6-10
      years, 42 of whom were selected for test-retest analysis. The behaviors of all
      206 children were rated during their dental appointments and compared to their
      questionnaire results. RESULTS: The internal consistency (Cronbach's alpha) was
      0.85, and the test-retest reliability (intraclass correlation) was 0.71. The
      Chinese version of the CFSS-DS showed good criterion validity; children who were
      uncooperative on the Frankl Scale had higher mean CFSS-DS scores (Z = 5.79).
      Through factorization, three factors emerged: (1) dental treatment, (2) hospital
      personnel, and (3) invasive dental procedures. Girls reported more fear than boys
      (21.79 vs 19.91), and children who had painful dental experiences reported more
      fear (30.87 vs 20.00). CONCLUSION: These results suggest that the CFSS-DS is
      reliable and valid and operates in China as it does in other cultures. Further
      studies should include school samples to evaluate children who may not go to the
      dentist.

PMID- 24730713
TI  - Abstracts of the 19th Annual Fall Scientific Meeting of the Sexual Medicine
      Society of North America, November 21-24 2013, New Orleans, Louisiana.

PMID- 24730714
TI  - Endoscopic large balloon sphincteroplasty is a useful, safe adjunct for difficult
      to treat choledocholithiasis.
AB  - BACKGROUND: The aim of this study was to assess the safety and efficacy of large
      balloon sphincteroplasty when used in conjunction with endoscopic biliary
      sphincterotomy during endoscopic retrograde cholangiopancreatography (ERCP) for
      therapy of choledocholithiasis. METHODS: A retrospective audit of all ERCP's
      performed for choledocholithiasis between January 2012 and October 2013 at one
      institution was performed. Procedures that utilized large balloon
      sphincteroplasty were compared with those underwent standard endoscopic stone
      extraction. Outcomes including stone clearance rate for the individual procedure
      type, post-ERCP complications and need for surgical exploration of the bile duct
      were documented. RESULTS: A total of 346 procedures on 306 patients that met the
      inclusion criteria were identified. Fifty-four (15.6%) procedures included large
      balloon sphincteroplasty and were compared with 292 (84.4%) procedures that used
      standard balloon extraction techniques. Despite those patients in the large
      balloon sphincteroplasty group having a higher rate of previous ERCP (33.3%
      versus 19.5%, P = 0.031) and a larger proportion of patients with stones greater
      than 10 mm (40.3% versus 11.3%, P < 0.001), the overall initial clearance rate
      was similar at 83%. Ultimately, only 14 out of 306 (4.6%) of all patients
      required surgical intervention. There was no significant difference in the rate
      of post-ERCP pancreatitis between the two groups (5.6% versus 3.8%, P = 0.466).
      CONCLUSION: Large balloon sphincteroplasty of the sphincter of Oddi is a safe and
      effective adjunct to endoscopic biliary sphincterotomy in difficult to treat
      choledocholithiasis. The current study demonstrated large balloon
      sphincteroplasty did not result in more complications despite a tendency to being
      used for larger stones.

PMID- 24730715
TI  - Commentary: ILAE Definition of Epilepsy.

PMID- 24730716
TI  - Interfacial energies for heterogeneous nucleation of calcium carbonate on mica
      and quartz.
AB  - Interfacial free energies often control heterogeneous nucleation of calcium
      carbonate (CaCO3) on mineral surfaces. Here we report an in situ experimental
      study of CaCO3 nucleation on mica (muscovite) and quartz, which allows us to
      obtain the interfacial energies governing heterogeneous nucleation. In situ
      grazing incidence small-angle X-ray scattering (GISAXS) was used to measure
      nucleation rates at different supersaturations. The rates were incorporated into
      classical nucleation theory to calculate the effective interfacial energies
      (alpha'). Ex situ Raman spectroscopy identified both calcite and vaterite as
      CaCO3 polymorphs; however, vaterite is the most probable heterogeneous nuclei
      mineral phase. The alpha' was 24 mJ/m(2) for the vaterite-mica system and 32
      mJ/m(2) for the vaterite-quartz system. The smaller alpha' of the CaCO3-mica
      system led to smaller particles and often higher particle densities on mica. A
      contributing factor affecting alpha' in our system was the smaller structural
      mismatch between CaCO3 and mica compared to that between CaCO3 and quartz. The
      extent of hydrophilicity and the surface charge could not explain the observed
      CaCO3 nucleation trend on mica and quartz. The findings of this study provide new
      thermodynamic parameters for subsurface reactive transport modeling and
      contribute to our understanding of mechanisms where CaCO3 formation on surfaces
      is of concern. 

PMID- 24730717
TI  - Long-term lithium treatment reduces glucose metabolism in the cerebellum and
      hippocampus of nondemented older adults: an [18F]FDG-PET study.
AB  - Lithium modulates several intracellular pathways related to neuroplasticity and
      resilience against neuronal injury. These properties have been consistently
      reported in experimental models, and involve the up-regulation of neurotrophic
      response and autophagy, and down-regulation of apoptosis, oxidative stress, and
      inflammation. Clinical and epidemiological studies in bipolar disorder show that
      acute treatment with lithium increases plasma concentrations of brain-derived
      neurotrophic factor, and long-term treatment lowers the risk of dementia.
      Neuroimaging studies indicate that lithium use is further associated with
      increased cortical thickness and larger hippocampal volumes. The objective of the
      present study was to evaluate whether these neurobiological properties of lithium
      reflect in increased regional brain glucose metabolism, as shown by [(18)F]FDG
      PET. Participants (n = 19) were nondemented older adults recruited at the end
      point of a controlled trial addressing clinical and biological effects of lithium
      in a sample of patients with amnestic mild cognitive impairment. Twelve patients
      who had received low-dose lithium carbonate for 4 years were compared to seven
      matched controls. Chronic lithium treatment was not associated with any
      significant increase in brain glucose metabolism in the studied areas.
      Conversely, we found a significant reduction in glucose uptake in several
      clusters of the cerebellum and in both hippocampi. These findings were not
      associated with any clinical evidence of toxicity. The clinical implications of
      the present findings need to be clarified by future controlled studies,
      particularly in the light of the potential use of lithium as a disease-modifying
      treatment approach for certain neurodegenerative disorders, namely, Alzheimer's
      disease and amyotrophic lateral sclerosis. 

PMID- 24730718
TI  - Negative affect improves the quality of memories: trading capacity for precision
      in sensory and working memory.
AB  - Research has shown that negative affect reduces working memory capacity.
      Commonly, this effect has been attributed to an allocation of resources to task
      irrelevant thoughts, suggesting that negative affect has detrimental consequences
      for working memory performance. However, rather than simply being a detrimental
      effect, the affect-induced capacity reduction may reflect a trading of capacity
      for precision of stored representations. To test this hypothesis, we induced
      neutral or negative affect and concurrently measured the number and precision of
      representations stored in sensory and working memory. Compared with neutral
      affect, negative affect reduced the capacity of both sensory and working memory.
      However, in both memory systems, this decrease in capacity was accompanied by an
      increase in precision. These findings demonstrate that observers unintentionally
      trade capacity for precision as a function of affective state and indicate that
      negative affect can be beneficial for the quality of memories.

PMID- 24730719
TI  - Individual differences in memory search and their relation to intelligence.
AB  - Attempts to understand why memory predicts intelligence have not fully leveraged
      state-of-the-art measures of recall dynamics. Using data from a multisession free
      recall study, we examine individual differences in measures of recall initiation
      and postinitiation transitions. We identify 4 sources of variation: a recency
      factor reflecting variation in the tendency to initiate recall from an item near
      the end of the list, a primacy factor reflecting a tendency to initiate from the
      beginning of the list, a temporal factor corresponding to transitions mediated by
      temporal associations, and a semantic factor corresponding to semantically
      mediated transitions. Together, these 4 factors account for 83% of the
      variability in overall recall accuracy, suggesting they provide a nearly complete
      picture of recall dynamics. We also show that these sources of variability
      account for over 80% of the variance shared between memory and intelligence. The
      temporal association factor was the most influential in predicting both recall
      accuracy and intelligence. We outline a theory of how controlled drift of
      temporal context may be critical across a range of cognitive activities.

PMID- 24730721
TI  - Autobiographical memory distributions for negative self-images: memories are
      organised around negative as well as positive aspects of identity.
AB  - The relationship between developmental experiences, and an individual's emerging
      beliefs about themselves and the world, is central to many forms of
      psychotherapy. People suffering from a variety of mental health problems have
      been shown to use negative memories when defining the self; however, little is
      known about how these negative memories might be organised and relate to negative
      self-images. In two online studies with middle-aged (N = 18; study 1) and young
      (N = 56; study 2) adults, we found that participants' negative self-images (e.g.,
      I am a failure) were associated with sets of autobiographical memories that
      formed clustered distributions around times of self-formation, in much the same
      pattern as for positive self-images (e.g., I am talented). This novel result
      shows that highly organised sets of salient memories may be responsible for
      perpetuating negative beliefs about the self. Implications for therapy are
      discussed. 

PMID- 24730722
TI  - Mary Seacole - the world's first nurse entrepreneur?

PMID- 24730724
TI  - Carriage of methicillin-resistant staphylococci by healthy companion animals in
      the US.
AB  - Antimicrobial-resistant staphylococci have been associated with wounded or ill
      companion animals, but little is known about the prevalence of resistant
      staphylococci among healthy animals. In this study, 276 healthy dogs and cats
      from veterinary clinics were tested for the presence of antimicrobial-resistant
      Staphylococcus spp. Isolates were tested for antimicrobial susceptibility and the
      presence of select resistance genes, and typed using Pulsed-Field Gel
      Electrophoresis (PFGE). Staphylococcus aureus and Staphylococcus pseudintermedius
      were also characterized using multilocus sequence typing (MLST), spa typing and
      SCCmec typing. Approximately 5% (14/276) of the animals were positive by
      enrichment for five species of staphylococci [Staph. aureus (n = 11), Staph.
      pseudintermedius (n = 4), Staphylococcus sciuri (n = 6), Staphylococcus simulans
      (n = 1) and Staphylococcus warneri (n = 1)]. Seventy-eight per cent (18/23) of
      staphylococci were resistant to oxacillin and also multidrug resistant
      (resistance to >= 2 antimicrobials). All Staph. aureus isolates were mecA+ and
      blaZ+, SCCmec type II, spa type t002, ST5 and clonal using PFGE. Staphylococcus
      pseudintermedius were SCCmec type IV or V, spa type t06 and ST170; two of the
      isolates were pvl(+) . These results suggest that healthy companion animals may
      be a reservoir of multidrug-resistant staphylococci, which may be transferred to
      owners and others who handle companion animals. SIGNIFICANCE AND IMPACT OF THE
      STUDY: In this study, antimicrobial-resistant coagulase-negative and coagulase
      positive staphylococci were isolated from various body sites on healthy dogs and
      cats. Resistance to 14 antimicrobials was observed including resistance to
      oxacillin; the majority of staphylococci were also multidrug resistant. Results
      from this study suggest that healthy dogs and cats may act as reservoirs of
      antimicrobial-resistant bacteria that may be transferred to people by simple
      interaction with the animals. Such carriage poses an underlying risk of
      infection, which should be considered during handling of healthy dogs and cats by
      pet owners and veterinary personnel.

PMID- 24730725
TI  - Antioxidant and DNA damage protective properties of anthocyanin-rich extracts
      from Hibiscus and Ocimum: a comparative study.
AB  - Anthocyanin extracts (AEs) from Ocimum tenuiflorum (leaf), Hibiscus rosa-sinensis
      (petal) and Hibiscus sabdariffa (calyx) were investigated and compared for in
      vitro antioxidant activity and DNA damage protective property. Total phenolic
      content (TPC) and total anthocyanin content (TAC) of the AEs were determined and
      the major anthocyanins were characterised. In vitro antioxidant activities were
      assessed by ferric-reducing antioxidant power (FRAP) assay, 2,2-diphenyl-1-picryl
      hydrazyl (DPPH) radical-scavenging activity, 2-deoxy-D-ribose degradation assay
      and lipid peroxidation assay. The protective property of the AEs was also
      examined against oxidative DNA damage by H2O2 and UV using pUC19 plasmid. All the
      AEs particularly those from O. tenuiflorum demonstrated efficient antioxidant
      activity and protected DNA from damage. Strong correlation between antioxidant
      capacity and TPC and TAC was observed. Significant correlation between
      antioxidant capacity and TPC and TAC ascertained that phenolics and anthocyanins
      were the major contributors of antioxidant activity.

PMID- 24730727
TI  - Structural, dynamic, and transport properties of concentrated aqueous sodium
      chloride solutions under an external static electric field.
AB  - In the absence of an external electric field, it has already been known that ion
      clusters are formed instantaneously in moderately concentrated ionic solutions.
      In this work, we use molecular dynamics (MD) simulations to investigate the
      changes of structural, dynamic, and transport properties in a sodium chloride
      solution under an external electric field from the ion cluster perspective. Our
      MD simulation results indicate that, with a strong external electric field E
      (>=0.1 V/nm) applied, ion clusters become smaller and less net charged, and the
      structures and dynamics as well as transport properties of the ion solution
      become anisotropic. The influence of the cluster structure and shell structure to
      transport properties was analyzed and the Einstein relation was found invalid in
      this system. 

PMID- 24730728
TI  - Population-based study of esophageal and small intestinal atresia/stenosis.
AB  - BACKGROUND: The aim of this study was to describe the prevalence of esophageal
      atresia/stenosis and small intestinal atresia/stenosis in Nagano, Japan, together
      with associated anomalies, prenatal diagnosis and survival. METHODS: A population
      based cohort study of the prevalence of esophageal atresia/stenosis and small
      intestinal atresia/stenosis was conducted in Nagano in January 1993-December
      2011. The Mann-Whitney test, chi(2) test and Kruskal-Wallis test were used to
      compare variables. P < 0.05 was considered statistically significant. RESULTS: In
      total, 74 cases of esophageal atresia/stenosis and 87 cases of small intestinal
      atresia/stenosis (31 duodenal, 56 jejuno-ileal) were identified. Prevalences were
      1.97 for esophageal atresia/stenosis and 2.23 for small intestinal
      atresia/stenosis (0.83 for duodenal atresia/stenosis and 1.49 for jejuno-ileal
      atresia/stenosis) per 10,000 births, respectively. The prevalence of esophageal
      atresia/stenosis increased significantly from 1993-2001 to 2002-2011 (relative
      risk [RR], 1.6), as did the prevalences of duodenal atresia/stenosis (RR, 2.2)
      and jejuno-ileal atresia/stenosis (RR, 3.1). Chromosomal anomalies, particularly
      trisomy 21, were seen significantly more often in association with duodenal
      atresia/stenosis (55%) than with esophageal atresia/stenosis (28%, P < 0.01) or
      jejuno-ileal atresia/stenosis (2%, P < 0.01). The proportion of patients
      associated with prenatally diagnosed chromosomal anomaly was higher compared to
      postnatal diagnosis (P < 0.01) in the esophageal atresia/stenosis group.
      CONCLUSION: The prevalence of esophageal and small intestinal atresia/stenosis
      increased significantly from 1993-2001 to 2002-2011. Prenatally diagnosed
      esophageal atresia/stenosis is associated with multiple anomalies, particularly
      chromosomal anomalies, compared to other small intestine atresia/stenosis.

PMID- 24730726
TI  - Hyperbaric oxygen, vasculogenic stem cells, and wound healing.
AB  - SIGNIFICANCE: Oxidative stress is recognized as playing a role in stem cell
      mobilization from peripheral sites and also cell function. RECENT ADVANCES: This
      review focuses on the impact of hyperoxia on vasculogenic stem cells and elements
      of wound healing. CRITICAL ISSUES: Components of the wound-healing process in
      which oxidative stress has a positive impact on the various cells involved in
      wound healing are highlighted. A slightly different view of wound-healing
      physiology is adopted by departing from the often used notion of sequential
      stages: hemostatic, inflammatory, proliferative, and remodeling and instead
      organizes the cascade of wound healing as overlapping events or waves pertaining
      to reactive oxygen species, lactate, and nitric oxide. This was done because
      hyperoxia has effects of a number of cell signaling events that converge to
      influence cell recruitment/chemotaxis and gene regulation/protein synthesis
      responses which mediate wound healing. FUTURE DIRECTIONS: Our alternative
      perspective of the stages of wound healing eases recognition of the multiple
      sites where oxidative stress has an impact on wound healing. This aids the focus
      on mechanistic events and the interplay among various cell types and biochemical
      processes. It also highlights the areas where additional research is needed.

PMID- 24730729
TI  - Comparing lipid membranes in different environments.
AB  - When engineering lipid membranes for applications, it is essential to
      characterize them to avoid artifacts introduced by manipulation and the
      experimental environment. Wide-angle X-ray scattering is a powerful structural
      characterization tool for well-ordered lipid systems. It reveals remarkable
      differences in rotational order parameters for samples prepared in different
      ways. New data and perspectives are presented here for multilamellar systems that
      support and extend the characterization work on unilamellar systems that is
      reported by Watkins et al. in this issue of ACS Nano. 

PMID- 24730731
TI  - Effect of exhaustive incremental treadmill effort on force generation
      repeatability in biathletes.
AB  - The authors examined how force generation repeatability changes as the result of
      incremental maximal test to volitional exhaustion by well-trained (VO2/kg [mL .
      kg(-1) . min(-1)] 62.55 +/- 5.27) individuals. 13 young biathletes (18.9 +/- 1.7
      years) performed isometric maximum voluntary contraction (IMVC) and submaximal
      targeted (98N) pushes against the force transducers by arms: elbow extension
      (EE), elbow flexion (EF) and legs: knee extensions (KE) in pre- and posttest
      conditions after incremental exhaustive test performed on treadmill. IMVC did not
      differ significantly between pre and posttest conditions for upper and
      statistically decrease in lower extremities measurements (p <.01). The mean force
      of 10 submaximal targeted force productions (F(mean); N) is similar for pre- and
      posttest measurements. Standard deviation of F(mean) (Fsd; N) and coefficient
      variation (CV;%) decrease statistically in elbows flexion p <.02 but not
      extension. The reduction of force repetition accuracy in left knee extension was
      noticed (p <.01). The fatigue induced by incremental running test decreases a
      magnitude of force production variability in specifically trained muscle groups
      in biathletes.

PMID- 24730730
TI  - Transcriptomic network support distinct roles of classical and non-classical
      monocytes in human.
AB  - Classical and non-classical monocytes are two well-defined subsets of monocytes
      displaying distinct roles. They differentially express numerous genes relevant to
      their primary role. Using five independent transcriptomic microarray datasets, we
      ruled out several inconsistent genes and identified common genes consistently
      overexpressed either in classical or non-classical monocytes. One hundred and
      eight genes were significantly increased in classical monocytes and are involved
      in bacterial defense, inflammation and atherosclerosis. Whereas the 74 genes
      overexpressed in non-classical monocytes are involved in cytoskeletal dynamics
      and invasive properties for enhanced motility and infiltration. These signatures
      unravel the biological functions of monocyte subsets. HIGHLIGHTS We compared five
      transcriptomic GEO datasets of human monocyte subsets. 108 genes in classical and
      74 genes in non-classical monocytes are upregulated. Upregulated genes in
      classical monocytes support anti-bacterial and inflammatory responses.
      Upregulated genes in non-classical monocytes support patrolling and infiltration
      functions. 

PMID- 24730732
TI  - Advanced liver fibrosis by transient elastography, fibrosis 4, and alanine
      aminotransferase/platelet ratio index among Asian hepatitis C with and without
      human immunodeficiency virus infection: role of vitamin D levels.
AB  - BACKGROUND AND AIM: Vitamin D insufficiency plays an important role in liver
      fibrosis in hepatitis C virus (HCV)-infected patients. We assessed liver fibrosis
      by transient elastography and 25 hydroxy vitamin D [25(OH)D] status in HCV
      infected patients, with (HIV/HCV) or without HIV co-infection (HCV) from
      Thailand. METHODS: Fibrosis stage was defined as mild (< 7.1 kPa); moderate (7.2
      9.4 kPa); severe (9.5-14 kPa), and cirrhosis (> 14 kPa). Hypovitaminosis D was
      defined as 25(OH)D < 30 ng/mL. Logistic regression analyses were used to assess
      predictors for significant fibrosis. Serum 25(OH) D levels, HCV genotypes (GT),
      interleukin-28B (IL28B) and HCV-RNA were assessed. RESULTS: A total of 331 HCV
      and 130 HIV/HCV patients were enrolled (70% male, 35% people who inject drugs
      [PWIDs]). HCV GT distribution was as follows: GT3 47%, GT1 34%, GT6 17%. IL-28B
      CC genotype (rs12979860) were found in 88% of HIV/HCV and 85% of HCV. In HCV,
      liver fibrosis was mild in 56.5%; moderate in 18.4%; severe in 12.4%; and
      cirrhosis in 12.7%. In HIV/HCV, these figures were 30.6%, 27.8%, 17.6%, and
      24.1%, respectively. Patients with significant fibrosis were more often male,
      older, with HIV infection, hypovitaminosis D, and less likely to be infected with
      GT6. Factors associated with significant fibrosis by multivariate analysis were
      HIV infection (adjusted odd ratio [95% confidential interval]: 2.67, 1.20-5.93),
      P = 0.016, Fib-4 score > 1.45 (6.30, 2.70-14.74), P < 0.001, and hypovitaminosis
      D (2.48, 1.09-5.67), P = 0.031. GT 6 was less likely to have advanced liver
      fibrosis (0.17, 0.05-0.65), P = 0.01. CONCLUSIONS: HIV infection, Fib-4 score >
      1.45, and hypovitaminosis D are strong and independent predictors for the
      presence of advanced fibrosis in our HCV-infected patients. These data highlight
      the urgent need of HCV treatment and vitamin D supplement in resource-limited
      settings.

PMID- 24730733
TI  - Dynamic kinetic asymmetric [3 + 2] annulation reactions of aminocyclopropanes.
AB  - We report the first example of a dynamic kinetic asymmetric [3 + 2] annulation
      reaction of aminocyclopropanes with both enol ethers and aldehydes. Using a Cu
      catalyst and a commercially available bisoxazoline ligand, cyclopentyl- and
      tetrahydrofurylamines were obtained in 69-99% yield and up to a 98:2 enantiomeric
      ratio using the same reaction conditions. The method gives access to important
      enantio-enriched nitrogen building blocks for the synthesis of bioactive
      compounds. 

PMID- 24730735
TI  - Stable individual differences in saccadic eye movements during reading,
      pseudoreading, scene viewing, and scene search.
AB  - Mean fixation duration and mean saccade amplitude during active viewing tasks
      differ from person to person. Previous studies have shown that these individual
      differences tend to be stable across at least some tasks, suggesting that they
      may reflect underlying traits associated with individuals. However, whether these
      individual differences are also stable over time has not been established. The
      present study established stable individual differences in mean fixation duration
      and mean saccade amplitude across 4 viewing tasks, showed that the observed
      individual differences are stable over several days, and extended these results
      to standard deviations of fixation duration and saccade amplitude. The results
      have implications for theories of eye movement control and for using eye movement
      characteristics as individual difference measures.

PMID- 24730734
TI  - Technical considerations for maize flour and corn meal fortification in public
      health: consultation rationale and summary.
AB  - Fortification is the purposeful addition of vitamins and minerals to foods during
      their industrial processing, as a way to improve the nutrition and health of
      populations who consume these foods. Twelve countries have mandatory maize (Zea
      mays subsp. Mays) flour or meal fortification. The World Health Organization
      (WHO) is updating evidence-informed guidelines for the fortification of staple
      foods in public health, including the fortification of maize flour and corn meal
      with iron and other micronutrients. Although there is limited experience with
      fortification of maize, mass fortification of maize flour with at least iron has
      been practiced for many years in several countries in the Americas and Africa:
      Brazil, Costa Rica, El Salvador, Kenya, Mexico, Nigeria, Rwanda, South Africa,
      Tanzania, Uganda, the United States, and Venezuela. The WHO, in collaboration
      with the Sackler Institute for Nutrition Science and the Flour Fortification
      Initiative (FFI), convened a consultation on technical considerations for
      fortification of maize flour and corn meal in public health in New York, New York
      on April 8-9, 2013 to provide input into the guideline-development process and to
      discuss technical considerations of the fortification processes for maize flour
      and corn meal. 

PMID- 24730736
TI  - Summary statistics of size: fixed processing capacity for multiple ensembles but
      unlimited processing capacity for single ensembles.
AB  - We assessed the processing capacity of establishing statistical summary
      representations (SSRs) of mean size in visual displays using the simultaneous
      sequential method. Four clusters of stimuli, each composed of several circles
      with various diameters, were presented around fixation. Observers searched for
      the cluster with the largest or smallest mean size. In the simultaneous
      condition, all four clusters were presented concurrently; in the sequential
      condition, the clusters appeared two at a time. We found that the processing
      capacity of SSRs for multiple ensembles was as extreme as a fixed-rate bottleneck
      process (Experiment 1). A control experiment confirmed that this was not caused
      by having to compare the results of multiple averaging processes (Experiment 2).
      In contrast to computing SSRs across ensembles, computing SSRs for a single
      ensemble using the same stimuli was consistent with unlimited-capacity processing
      (Experiment 3). Contrary to existing claims, summary representations appear to be
      extracted independently for items within single ensembles but not multiple
      ensembles. A developing understanding of capacity limitations in perceptual
      processing is discussed.

PMID- 24730737
TI  - Unloading and reloading working memory: attending to one item frees capacity.
AB  - During the retention interval of a working memory task, presenting a retro-cue
      directs attention to 1 of the items in working memory. Testing the cued item
      leads to faster and more accurate responses. We contrasted 5 explanations of this
      benefit: (a) removal of noncued items, (b) strengthening of the cued item, (c)
      protection from probe interference, (d) protection from degradation, and (e)
      prioritization during the decision process. Experiment 1 showed that retro-cues
      reduced the set size effect in a visual recognition task, and did so increasingly
      with more time available to use the retro-cue. This finding is predicted only by
      Hypotheses 1 and 2. Hypotheses 3 through 5 were ruled out as explanations of the
      retro-cue benefit in this experiment. In Experiments 2 and 3, participants
      encoded 2 sequentially presented memory sets. In half of the trials, 1 item from
      the first set was retro-cued during the interset interval. Retro-cues improved
      memory for the second set. This reloading benefit is predicted only by the
      removal hypothesis: Irrelevant contents are removed from working memory, freeing
      capacity to encode new contents. Experiment 3 also yielded evidence that
      strengthening of the cued item might contribute to the retro-cue effect.

PMID- 24730738
TI  - In competition for the attentional template: can multiple items within visual
      working memory guide attention?
AB  - Recent studies have revealed that the deployment of attention can be biased by
      the content of visual working memory (VWM), but that stored memories do not
      always interact with attention. This has led to a model which proposes a division
      within VWM between a single active template that interacts with perception and
      multiple accessory representations that do not. The present study was designed to
      study whether multiple memory representations are able to bias attention.
      Participants performed a visual search task while maintaining a variable number
      of colors in VWM. Consistent with earlier findings, we observed increased
      attentional capture by memory related distractors when VWM was filled with a
      single item. However, memory related capture was no longer present for memory
      loads beyond a single item. The absence of memory related capture at higher VWM
      loads was independent of individual VWM capacity, nor was it attributable to
      weaker encoding, forgetting, or reduced precision of memory representations. When
      analyses were limited to those trials in which participants had a relatively
      precise memory, there was still no sign of attentional guidance at higher loads.
      However, when observers were cued toward a specific memory item after encoding,
      interference with search returned. These results are consistent with a
      distinction within VWM between representations that interact with perception and
      those that do not, and show that only a single VWM representation at a time can
      interact with visual attention.

PMID- 24730739
TI  - Role of attentional tags in working memory-driven attentional capture.
AB  - Recent studies have demonstrated that the contents of working memory capture
      attention when performing a visual search task. However, it remains an intriguing
      and unresolved question whether all kinds of items stored in working memory
      capture attention. The present study investigated this issue by manipulating the
      attentional tags (target or distractor) associated with information maintained in
      working memory. The results showed that working memory-driven attentional capture
      is a flexible process, and that attentional tags associated with items stored in
      working memory do modulate attentional capture. When items were tagged as a
      target, they automatically captured attention; however, when items were tagged as
      a distractor, attentional capture was reduced.

PMID- 24730740
TI  - Short-term perceptual learning in visual conjunction search.
AB  - Although some studies showed that training can improve the ability of cross
      dimension conjunction search, less is known about the underlying mechanism.
      Specifically, it remains unclear whether training of visual conjunction search
      can successfully bind different features of separated dimensions into a new
      function unit at early stages of visual processing. In the present study, we
      utilized stimulus specificity and generalization to provide a new approach to
      investigate the mechanisms underlying perceptual learning (PL) in visual
      conjunction search. Five experiments consistently showed that after 40 to 50 min
      of training of color-shape/orientation conjunction search, the ability to search
      for a certain conjunction target improved significantly and the learning effects
      did not transfer to a new target that differed from the trained target in both
      color and shape/orientation features. However, the learning effects were not
      strictly specific. In color-shape conjunction search, although the learning
      effect could not transfer to a same-shape different-color target, it almost
      completely transferred to a same-color different-shape target. In color
      orientation conjunction search, the learning effect partly transferred to a new
      target that shared same color or same orientation with the trained target.
      Moreover, the sum of transfer effects for the same color target and the same
      orientation target in color-orientation conjunction search was algebraically
      equivalent to the learning effect for trained target, showing an additive
      transfer effect. The different transfer patterns in color-shape and color
      orientation conjunction search learning might reflect the different complexity
      and discriminability between feature dimensions. These results suggested a
      feature-based attention enhancement mechanism rather than a unitization mechanism
      underlying the short-term PL of color-shape/orientation conjunction search.

PMID- 24730741
TI  - Taking aim at the Muller-Lyer goalkeeper illusion: an illusion bias in action
      that originates from the target not being optically specified.
AB  - Van der Kamp and Masters (2008) reported that goalkeeper postures that mimic the
      Muller-Lyer (1889) illusion affect the location of handball penalty throws. In
      four experiments, we aimed to verify that the effects on throwing are consistent
      with an illusory bias (Experiments 1 and 2), and to examine how these
      observations can be understood in the context of Milner and Goodale's (1995,
      2008) two-visual systems model (Experiments 3 and 4). Experiments 1 and 2
      confirmed that the goalkeeper Muller-Lyer posture may indeed induce an illusory
      bias in throwing, implying that allocentric information is used in far-aiming
      action tasks. Experiment 3 demonstrated that the bias was not related to a
      participant's throwing skill. Experiment 4 suggested that an absence of visual
      information to instantaneously specify target location may have induced use of
      context-dependent allocentric information, causing the throwing bias. The results
      are discussed in the context of recent debates about the roles of the two-visual
      systems in perception and action. It is suggested that the two systems are first
      and foremost perceptual systems that serve the pickup of different sources of
      information.

PMID- 24730742
TI  - Dual-route model of the effect of head orientation on perceived gaze direction.
AB  - Previous studies on gaze perception have identified 2 opposing effects of head
      orientation on perceived gaze direction-1 repulsive and the other attractive.
      However, the relationship between these 2 effects has remained unclear. By using
      a gaze categorization task, the current study examined the effect of head
      orientation on the perceived direction of gaze in a whole-head condition and an
      eye-region condition. We found that the perceived direction of gaze was generally
      biased in the opposite direction to head orientation (a repulsive effect).
      Importantly, the magnitude of the repulsive effect was more pronounced in the eye
      region condition than in the whole-head condition. Based on these findings, we
      developed a dual-route model, which proposes that the 2 opposing effects of head
      orientation occur through 2 distinct routes. In the framework of this dual-route
      model, we explain and reconcile the findings from previous studies, and provide a
      functional account of attractive and repulsive effects and their interaction.

PMID- 24730743
TI  - Dynamics of visibility, confidence, and choice during eye movements.
AB  - We study the dynamics of objective and subjective measures of visibility and
      choice in brief presentations occurring within a fixation during free eye
      movements. We show that brief presentations yield homogeneous levels of
      performance in a window that extends almost throughout the entire fixation.
      Instead, confidence judgments vary for presentations occurring at different
      moments of the fixations. When the target occurs close to the onset of the
      fixation, it is reported accurately but with lower values of confidence; when it
      occurs close to the end of the fixation, it is reported with high confidence
      (Experiments 1 and 2). Consistently, in experiments in which participants can
      freely choose to report items, we observe a report bias toward the end of the
      fixation, where the maximum of confidence occurs for experiments with a single
      target (Experiments 3 and 4). Hence, these results suggest that confidence is not
      merely a measure of accumulated stimulus energy but instead varies reflecting an
      endogenous integration process by which later stimuli are assigned greater
      confidence.

PMID- 24730744
TI  - Information for coarticulation: Static signal properties or formant dynamics?
AB  - Perception of a speech segment changes depending on properties of surrounding
      segments in a phenomenon called compensation for coarticulation (Mann, 1980). The
      nature of information that drives these perceptual changes is a matter of debate.
      One account attributes perceptual shifts to low-level auditory system contrast
      effects based on static portions of the signal (e.g., third formant [F3] center
      or average frequency; Lotto & Kluender, 1998). An alternative account is that
      listeners' perceptual shifts result from listeners attuning to the acoustic
      effects of gestural overlap and that this information for coarticulation is
      necessarily dynamic (Fowler, 2006). In a pair of experiments, we used sinewave
      speech precursors to investigate the nature of information for compensation for
      coarticulation. In Experiment 1, as expected by both accounts, we found that
      sinewave speech precursors produce shifts in following segments. In Experiment 2,
      we investigated whether effects in Experiment 1 were driven by static F3 offsets
      of sinewave speech precursors, or by dynamic relationships among their formants.
      We temporally reversed F1 and F2 in sinewave precursors, preserving static F3
      offset and average F1, F2 and F3 frequencies, but disrupting dynamic formant
      relationships. Despite having identical F3s, selectively reversed precursors
      produced effects that were significantly smaller and restricted to only a small
      portion of the continuum. We conclude that dynamic formant relations rather than
      static properties of the precursor provide information for compensation for
      coarticulation.

PMID- 24730745
TI  - The same-location cost is unrelated to attentional settings: an object-updating
      account.
AB  - What mechanisms allow us to ignore salient yet irrelevant visual information has
      been a matter of intense debate. According to the contingent-capture hypothesis,
      such information is filtered out, whereas according to the salience-based
      account, it captures attention automatically. Several recent studies have
      reported a same-location cost that appears to fit neither of these accounts.
      These showed that responses may actually be slower when the target appears at the
      location just occupied by an irrelevant singleton distractor. Here, we
      investigated the mechanisms underlying this same-location cost. Our findings show
      that the same-location cost is unrelated to automatic attentional capture or
      strategic setting of attentional priorities, and therefore invalidate the feature
      based inhibition and fast attentional disengagement accounts of this effect. In
      addition, we show that the cost is wiped out when the cue and target are not
      perceived as parts of the same object. We interpret these findings as indicating
      that the same-location cost has been previously misinterpreted by both bottom-up
      and top-down theories of attentional capture. We propose that it is better
      understood as a consequence of object updating, namely, as the cost of updating
      the information stored about an object when this object changes across time.

PMID- 24730746
TI  - Slippage theory and the flanker paradigm: an early-selection account of selective
      attention failures.
AB  - In the flanker paradigm, participants identify a target letter while attempting
      to ignore an irrelevant flanker. When the identity of this flanker mismatches the
      target, target identification is slowed (called the flanker compatibility
      effect). Interestingly, reducing the array set size greatly increases flanker
      compatibility effects. This finding inspired 2 prominent explanations: perceptual
      load (mandatory capacity spillover) and dilution (visual interference). However,
      an alternative explanation, based on early selection theory and attention capture
      research, can also explain the data pattern. According to this "slippage"
      account, observers sometimes accidentally allocate spatial attention to the
      flanker (see Lachter, Forster, & Ruthruff, 2004), especially when the flanker has
      the property used to find the target (cf. contingent capture). In Experiments 1
      through 4, deterring slippage to the flanker nearly eliminated flanker
      compatibility effects, even at the low set size. In Experiment 5, promoting
      slippage to the flanker dramatically enhanced compatibility effects, even at the
      high set size. Thus, slippage strongly modulates flanker effects and can, by
      itself, readily explain the impact of set size. The perceptual load and dilution
      accounts are, at best, incomplete, and, at worst, not needed.

PMID- 24730747
TI  - Impact of oral mucosal conditions on oral health-related quality of life in
      preschool children: a hierarchical approach.
AB  - OBJECTIVE: To determine the impact of oral mucosal conditions on OHRQoL in
      preschool children. METHODS: A cross-sectional study was carried out with a
      selected representative sample of 724 children aged 2-5 years and their
      parents/caregivers. Data were collected through interviews with
      parents/caregivers, who also answered the B-ECOHIS. A clinical oral examination
      was performed to determine oral mucosal conditions, dental caries, dental trauma,
      and malocclusion. Data analysis involved descriptive statistics, the Kolmogorov
      Smirnov normality test, the Mann-Whitney U-test and hierarchically adjusted
      Poisson regression models (P < 0.05, 95% CI). RESULTS: The prevalence of oral
      mucosal conditions was 50.7%, the most prevalent of which were melanotic macules
      (17.8%), oral ulcers (11.0%), Fordyce's spots (9.4%), geographic tongue (5.2%),
      fissured tongue (1.9%), median rhomboid glossitis (1.8%), and fistula (1.4%). In
      the final multivariate model, child with 5 years of age (RR = 1.60; 95% CI: 1.08
      2.38; P = 0.020), with presence of fistula (RR = 1.94; 95% CI: 1.27-2.95; P =
      0.002), and with dental caries (RR = 2.58; 95% CI: 2.00-3.35; P < 0.001) had a
      negative impact on children's OHRQoL. CONCLUSION: Child with 5 years of age,
      presence of fistula, and dental caries were associated with a negative impact on
      the quality of life of preschool children.

PMID- 24730748
TI  - Commentary: ILAE definition of epilepsy.

PMID- 24730749
TI  - DNA polymorphisms and transcript abundance of PRKAG2 and phosphorylated AMP
      activated protein kinase in the rumen are associated with gain and feed intake in
      beef steers.
AB  - Beef steers with variation in feed efficiency phenotypes were evaluated
      previously on a high-density SNP panel. Ten markers from rs110125325-rs41652818
      on bovine chromosome 4 were associated with average daily gain (ADG). To identify
      the gene(s) in this 1.2-Mb region responsible for variation in ADG, genotyping
      with 157 additional markers was performed. Several markers (n = 41) were
      nominally associated with ADG, and three of these, including the only marker to
      withstand Bonferroni correction, were located within the protein kinase, AMP
      activated, gamma 2 non-catalytic subunit (PRKAG2) gene. An additional population
      of cross-bred steers (n = 406) was genotyped for validation. One marker located
      within the PRKAG2 loci approached a significant association with gain. To
      evaluate PRKAG2 for differences in transcript abundance, we measured expression
      in the liver, muscle, rumen and intestine from steers (n = 32) with extreme feed
      efficiency phenotypes collected over two seasons. No differences in PRKAG2
      transcript abundance were detected in small intestine, liver or muscle.
      Correlation between gene expression level of PRKAG2 in rumen and average daily
      feed intake (ADFI) was detected in both seasons (P < 0.05); however, the
      direction differed by season. Lastly, we evaluated AMP-activated protein kinase
      (AMPK), of which PRKAG2 is a subunit, for differences among ADG and ADFI and
      found that the phosphorylated form of AMPK was associated with ADFI in the rumen.
      These data suggest that PRKAG2 and its mature protein, AMPK, are involved in feed
      efficiency traits in beef steers. This is the first evidence to suggest that
      rumen AMPK may be contributing to ADFI in cattle.

PMID- 24730750
TI  - Laparoscopic versus robotic-assisted radical prostatectomy: an Australian single
      surgeon series.
AB  - BACKGROUND: In Australia, robotic-assisted radical prostatectomy (RARP) has
      steadily replaced open and laparoscopic surgery in the management of localized
      prostate cancer. Given the increased cost of this technology, we aimed to compare
      the perioperative, pathological, oncological and functional outcomes as well as
      short-term complications of laparoscopic and RARP. METHODS: We performed a
      retrospective review of prospectively collected data on 200 consecutive patients
      during the transition of a single surgeon (DM) from pure laparoscopic (n = 100)
      to RARP (n = 100) between September 2007 and March 2011. RESULTS: Median
      operative time and estimated blood loss were the same for both surgical
      approaches, 195 min (P = 0.29) and 300 mL (P = 0.88) respectively. Median length
      of hospital stay was shorter for RARP (P = 0.003). Complication rates were not
      statistically different between groups. There was no significant difference in
      positive surgical margin rates in pT2 (P = 0.36) or pT3 disease (0.99) or
      biochemical recurrence rate between groups (P = 0.14). The 12 months continence
      rate was improved with RARP compared with laparoscopic radical prostatectomy (93%
      versus 82%; P = 0.025). The potency rate was 56% and 74% at 12 months after
      laparoscopic radical prostatectomy and RARP respectively (P = 0.12) for a
      bilateral nerve sparing procedure. CONCLUSION: We conclude from our single
      surgeon comparative series that the robotic approach results in a significantly
      shorter length of hospital stay and improved 12 months continence rates and
      demonstrated a trend towards better potency rates. Complications, positive
      surgical margin rates and the requirement for adjuvant therapy are all improved
      with the robotic approach but did not show statistically significant differences.

PMID- 24730751
TI  - New strategy to enhance phosphate removal from water by hydrous manganese oxide.
AB  - Hydrous manganese oxide (HMO) is generally negatively charged at circumneutral pH
      and cannot effectively remove anionic pollutants such as phosphate. Here we
      proposed a new strategy to enhance HMO-mediated phosphate removal by immobilizing
      nano-HMO within a polystyrene anion exchanger (NS). The resultant nanocomposite
      HMO@NS exhibited substantially enhanced phosphate removal in the presence of
      sulfate, chloride, and nitrate at greater levels. This is mainly attributed to
      the pHpzc shift from 6.2 for the bulky HMO to 10.5 for the capsulated HMO
      nanoparticles, where HMO nanoparticles are positively charged at neutral pH. The
      ammonium groups of NS also favor phosphate adsorption through the Donnan effect.
      Cyclic column adsorption experiment indicated that the fresh HMO@NS could treat
      460 bed volumes (BV) of a synthetic influent (from the initial concentration of 2
      mg P[PO4(3-)]/L to 0.5 mg P[PO4(3-)]/L), while only 80 BV for NS. After the first
      time of regeneration by NaOH-NaCl solution, the capacity of HMO@NS was lowered to
      ~ 300 BV and then kept constant for the subsequent 5 runs, implying the presence
      of both the reversible and irreversible adsorption sites of nano-HMO. Additional
      column adsorption feeding with a real bioeffluent further validated great
      potential of HMO@NS in advanced wastewater treatment. This study may provide an
      alternative approach to expand the usability of other metal oxides in water
      treatment.

PMID- 24730752
TI  - Barriers to and facilitators of sports participation for people with physical
      disabilities: a systematic review.
AB  - Most people with physical disabilities do not participate in sports regularly,
      which could increase the chances of developing secondary health conditions.
      Therefore, knowledge about barriers to and facilitators of sports participation
      is needed. Barriers and facilitators for people with physical disabilities other
      than amputation or spinal cord injuries (SCI) are unknown. The aim of this study
      was to provide an overview of the literature focusing on barriers to and
      facilitators of sports participation for all people with various physical
      disabilities. Four databases were searched using MeSH terms and free texts up to
      April 2012. The inclusion criteria were articles focusing on people with physical
      disabilities, sports and barriers and/or facilitators. The exclusion criteria
      were articles solely focusing on people with cognitive disabilities, sensory
      impairments or disabilities related to a recent organ transplant or similar
      condition. Fifty-two articles were included in this review, with 27 focusing on
      people with SCI. Personal barriers were disability and health; environmental
      barriers were lack of facilities, transport and difficulties with accessibility.
      Personal facilitators were fun and health, and the environmental facilitator was
      social contacts. Experiencing barriers to and facilitators of sports
      participation depends on age and type of disability and should be considered when
      advising people about sports. The extent of sports participation for people with
      physical disabilities also increases with the selection of the most appropriate
      sport. 

PMID- 24730753
TI  - A systematic review: non-pharmacological interventions in treating pain in
      patients with advanced cancer.
AB  - AIMS: To assess and synthesize the evidence of the effects and safety of non
      pharmacological interventions in treating pain in patients with advanced cancer.
      BACKGROUND: Pain is a common symptom experienced by patients with advanced
      cancer; the treatment of such pain is often suboptimal. To manage it, non
      pharmacological interventions are recommended after pharmacological treatments
      have been re-evaluated and modified. However, there remains a lack of knowledge
      about the effects and safety of such interventions. DESIGN: A systematic review
      was conducted based on the procedure of the Centre of Reviews and Dissemination.
      DATA SOURCES: Research papers published between 2000-2013 were identified from
      the following databases: CINAHL, MEDIC, MEDLINE (Ovid) and PsycINFO. The
      references in the selected studies were searched manually. REVIEW METHODS: The
      studies selected were reviewed for quality, using Cochrane Effective Practice and
      Organisation of Care Review Group risk of bias assessment criteria. RESULTS:
      There was limited evidence that some of the non-pharmacological interventions
      were promising with respect to reducing cancer pain. Relatively, few adverse
      events were reported as a result of using such interventions. CONCLUSION: It was
      not possible to draw conclusions about the effects and safety of the non
      pharmacological interventions in reducing cancer pain. Some interventions showed
      promising short-term effects, but there is a need for more rigorous trials.
      Qualitative studies are required to collect information about patients'
      perceptions. There are several research gaps: we found no studies about music,
      spiritual care, hypnosis, active coping training, cold or ultrasonic stimulation.

PMID- 24730754
TI  - Vitamin D and central hypersensitivity in patients with chronic pain.
AB  - BACKGROUND: Low vitamin D is implicated in various chronic pain conditions with,
      however, inconclusive findings. Vitamin D might play an important role in
      mechanisms being involved in central processing of evoked pain stimuli but less
      so for spontaneous clinical pain. OBJECTIVE: This study aims to examine the
      relation between low serum levels of 25-hydroxyvitamin D3 (25-OH D) and
      mechanical pain sensitivity. DESIGN: We studied 174 patients (mean age 48 years,
      53% women) with chronic pain. A standardized pain provocation test was applied,
      and pain intensity was rated on a numerical analogue scale (0-10). The widespread
      pain index and symptom severity score (including fatigue, waking unrefreshed, and
      cognitive symptoms) following the 2010 American College of Rheumatology
      preliminary diagnostic criteria for fibromyalgia were also assessed. Serum 25-OH
      D levels were measured with a chemiluminescent immunoassay. RESULTS: Vitamin
      deficiency (25-OH D < 50 nmol/L) was present in 71% of chronic pain patients;
      another 21% had insufficient vitamin D (25-OH D < 75 nmol/L). After adjustment
      for demographic and clinical variables, there was a mean +/- standard error of
      the mean increase in pain intensity of 0.61 +/- 0.25 for each 25 nmol/L decrease
      in 25-OH D (P = 0.011). Lower 25-OH D levels were also related to greater symptom
      severity (r = -0.21, P = 0.008) but not to the widespread pain index (P = 0.83)
      and fibromyalgia (P = 0.51). CONCLUSIONS: The findings suggest a role of low
      vitamin D levels for heightened central sensitivity, particularly augmented pain
      processing upon mechanical stimulation in chronic pain patients. Vitamin D seems
      comparably less important for self-reports of spontaneous chronic pain.

PMID- 24730755
TI  - Blast-induced traumatic brain injury of goats in confined space.
AB  - OBJECTIVE: To study blast-induced traumatic brain injury (bTBI) characteristics
      in confined space. METHODS: The goats were placed at the column-like buildings
      with trinitrotoluene (TNT) as the source of the blast wave. The pressure was
      recorded at 2-8 m from the explosion center. The systemic physiology,
      electroencephalogram (EEG), serum level of S-100beta, and neuron specific enolase
      (NSE) were determined pre and post the exposure. Neuroanatomy and neuropathology
      were observed 4 hours after the exposure. RESULTS: The blast waveform was
      composed of two peaks from the incident and reflection wave with a range of
      pressure-duration from 555/913 kPa-0.663 milliseconds at 2 m to 45/71 kPa
      2.7/2.367 milliseconds at 8 m. At 2 m, the goats experienced brain depression
      while the heart rate and respiratory rate concomitantly increased with bloody
      foam fluid emission from the nose and the mouth. Of the goats, 88.89% were
      burned. The distinctive gross neuroanatomical changes were congestive expansion
      of surface vessels on the hemisphere cerebellum and brainstem along with
      subarachnoid hemorrhage on the frontal lobe, mesencephalon, and brainstem.
      Subarachnoid hemorrhage, enlarged perivascular space, vascular dilatation and
      congestion, and parenchymal hemorrhagic could be easily observed microscopically.
      High amplitude and low frequency of waveforms appeared in the EEG. The serum
      concentration of S-100beta and NSE were elevated. Although these
      pathophysiological changes diminished with increasing distance from the explosive
      center, these changes existed for the 8 m subjects. CONCLUSIONS: Blast-induced
      traumatic brain injury can be induced by a complex blast wave with a pressure and
      duration of 45/71 kPa and 2.7/2.367 milliseconds. Its severity is related to the
      features and waveforms of the blast.

PMID- 24730756
TI  - Impact of inflammation, emphysema, and smoking cessation on V/Q in mouse models
      of lung obstruction.
AB  - BACKGROUND: Chronic obstructive pulmonary disease (COPD) is known to greatly
      affect ventilation (V) and perfusion (Q) of the lung through pathologies such as
      inflammation and emphysema. However, there is little direct evidence regarding
      how these pathologies contribute to the V/Q mismatch observed in COPD and models
      thereof. Also, little is known regarding how smoking cessation affects V/Q
      relationships after inflammation and airspace enlargement have become
      established. To this end, we have quantified V/Q on a per-voxel basis using
      single photon emission computed tomography (SPECT) in mouse models of COPD and
      lung obstruction. METHODS: Three distinct murine models were used to investigate
      the impact of different pathologies on V/Q, as measured by SPECT.
      Lipopolysaccharide (LPS) was used to produce neutrophilic inflammation, porcine
      pancreatic elastase (PPE) was used to produce emphysema, and long-term cigarette
      smoke (CS) exposure and cessation were used to investigate the combination of
      these pathologies. RESULTS: CS exposure resulted in an increase in mononuclear
      cells and neutrophils, an increase in airspace enlargement, and an increase in
      V/Q mismatching. The inflammation produced by LPS was more robust and
      predominantly neutrophilic, compared to that of cigarette smoke; nevertheless,
      inflammation alone caused V/Q mismatching similar to that seen with long-term CS
      exposure. The emphysematous lesions caused by PPE administration were also
      capable of causing V/Q mismatch in the absence of inflammation. Following CS
      cessation, inflammatory cell levels returned to those of controls and, similarly,
      V/Q measures returned to normal despite evidence of persistent mild airspace
      enlargement. CONCLUSIONS: Both robust inflammation and extensive airspace
      enlargement, on their own, were capable of producing V/Q mismatch. As CS
      cessation resulted in a return of V/Q mismatching and inflammatory cell counts to
      control levels, lung inflammation is likely a major contributor to V/Q mismatch
      observed in the cigarette smoke exposure model as well as in COPD patients. This
      return of V/Q mismatching to control values also took place in the presence of
      mild airspace enlargement, indicating that emphysematous lesions must be of a
      larger volume before affecting the lung significantly. Early smoking cessation is
      therefore critical before emphysema has an irreversible impact on gas exchange.

PMID- 24730757
TI  - Effect of backward walking treadmill training on walking capacity after stroke: a
      randomized clinical trial.
AB  - RATIONALE: Residual walking deficits are common in people after stroke. Treadmill
      training can increase walking speed and walking distance. A new way to increase
      the challenge of walking is to walk backwards. Backward treadmill walking may
      provide advantages by promoting improvement in balance, walking spatiotemporal
      parameters and quality that may reflect in improving walking distance. AIM: This
      study will test the hypothesis that backward treadmill walking is superior to
      forward treadmill walking in improving walking capacity, walking parameters,
      quality and balance in people with stroke. DESIGN: A prospective, single-blinded,
      randomized trial will randomly allocate 88 community-dwelling people after stroke
      into either an experimental or control group. The experimental group will
      undertake 30-min sessions of backward treadmill walking, three-days/week for six
      weeks, while the control group will undertake the same dose of forward treadmill
      walking. Training will begin at the baseline overground walking speed and will
      increase each week by 10% of baseline speed. STUDY OUTCOMES: The primary outcome
      will be distance walked in the 6-min Walk Test. Secondary outcomes will be
      walking speed, step length, cadence, and one-leg stance time. Outcomes will be
      collected by a researcher blinded to group allocation at baseline (Week 0), at
      the end of training period (Week 6), and three-months after the cessation of
      intervention (Week 18). DISCUSSION: If backward treadmill walking can improve
      walking capacity more than forward treadmill training in stroke, it may have
      broader implications because walking capacity has been shown to predict physical
      activity level and community participation.

PMID- 24730758
TI  - Asymmetric chlorocyclization of indole-3-yl-benzamides for the construction of
      fused indolines.
AB  - (DHQD)2PHAL catalyzed enantioselective chlorocyclization of indole-3-yl
      benzamides was realized. Fused indolines containing a continuous quaternary
      carbon center and tertiary carbon center were obtained in good yields with
      excellent enantioselectivity (up to 98% yield and >99% ee). 

PMID- 24730759
TI  - Hypolipidaemic and antioxidant properties of ethanol extract from Flos populi.
AB  - This study was undertaken to evaluate antihyperlipidaemic and in vitro
      antioxidant activity of ethanolic extract of Flos populi (EFP). The results
      demonstrated that EFP contains 78.5% flavonoids and 10.4% phenolics, and it
      exhibited free radical-scavenging activity on 2,2-diphenyl-picrylhydrazyl (IC50
      36.40 +/- 0.62 MUg/mL) and high reducing power (EC50 206.32 +/- 1.6l MUg/mL)
      under in vitro chemical assays. And irrespective of prophylactic administration
      or remedial administration, in high fat diet-induced hyperlipidaemic mice, oral
      treatment with EFP produced a decrease in the levels of serum total cholesterol,
      triglycerides, low-density lipoprotein-cholesterol and increase in high-density
      lipoprotein-cholesterol. In a word, in high fat diet-fed hyperlipidaemic mice,
      EFP (100, 200 and 400 mg/kg) significantly altered the plasma lipid levels to
      near normal. These results support a potential effect of EFP in cardiovascular
      disease.

PMID- 24730760
TI  - Reply: To PMID 23834617.

PMID- 24730762
TI  - Exploring the effect of power law social popularity on language evolution.
AB  - We evaluate the effect of a power-law-distributed social popularity on the origin
      and change of language, based on three artificial life models meticulously
      tracing the evolution of linguistic conventions including lexical items,
      categories, and simple syntax. A cross-model analysis reveals an optimal social
      popularity, in which the lambda value of the power law distribution is around
      1.0. Under this scaling, linguistic conventions can efficiently emerge and widely
      diffuse among individuals, thus maintaining a useful level of mutual
      understandability even in a big population. From an evolutionary perspective, we
      regard this social optimality as a tradeoff among social scaling, mutual
      understandability, and population growth. Empirical evidence confirms that such
      optimal power laws exist in many large-scale social systems that are constructed
      primarily via language-related interactions. This study contributes to the
      empirical explorations and theoretical discussions of the evolutionary relations
      between ubiquitous power laws in social systems and relevant individual
      behaviors.

PMID- 24730763
TI  - Cracking the egg: virtual embryogenesis of real robots.
AB  - All multicellular living beings are created from a single cell. A developmental
      process, called embryogenesis, takes this first fertilized cell down a complex
      path of reproduction, migration, and specialization into a complex organism
      adapted to its environment. In most cases, the first steps of the embryogenesis
      take place in a protected environment such as in an egg or in utero. Starting
      from this observation, we propose a new approach to the generation of real
      robots, strongly inspired by living systems. Our robots are composed of tens of
      specialized cells, grown from a single cell using a bio-inspired virtual
      developmental process. Virtual cells, controlled by gene regulatory networks,
      divide, migrate, and specialize to produce the robot's body plan (morphology),
      and then the robot is manually built from this plan. Because the robot is as easy
      to assemble as Lego, the building process could be easily automated.

PMID- 24730764
TI  - Evolving functional and structural dynamism in coupled Boolean networks.
AB  - This article uses a recently presented abstract, tunable Boolean regulatory
      network model to further explore aspects of mobile DNA, such as transposons. The
      significant role of mobile DNA in the evolution of natural systems is becoming
      increasingly clear. This article shows how dynamically controlling network node
      connectivity and function via transposon-inspired mechanisms can be selected for
      to significant degrees under coupled regulatory network scenarios, including when
      such changes are heritable. Simple multicellular and coevolutionary versions of
      the model are considered.

PMID- 24730765
TI  - Generation of diversity in a reaction-diffusion-based controller.
AB  - A controller of biological or artificial organism (e.g., in bio-inspired cellular
      robots) consists of a number of processes that drive its dynamics. For a system
      of processes to perform as a successful controller, different properties can be
      mentioned. One of the desirable properties of such a system is the capability of
      generating sufficiently diverse patterns of outputs and behaviors. A system with
      such a capability is potentially adaptable to perform complicated tasks with
      proper parameterizations and may successfully reach the solution space of
      behaviors from the point of view of search and evolutionary algorithms. This
      article aims to take an early step toward exploring this capability at the levels
      of individuals and populations by introducing measures of diversity generation
      and by evaluating the influence of different types of processes on diversity
      generation. A reaction-diffusion-based controller called the artificial
      homeostatic hormone system (AHHS) is studied as a system consisting of different
      processes with various domains of functioning (e.g., internal or external to the
      control unit). Various combinations of these processes are investigated in terms
      of diversity generation at levels of both individuals and populations, and the
      effects of the processes are discussed representing different influences for the
      processes. A case study of evolving a multimodular AHHS controller with all the
      various process combinations is also investigated, representing the relevance of
      the diversity generation measures and practical scenarios.

PMID- 24730766
TI  - Simulated predator attacks on flocks: a comparison of tactics.
AB  - It is not exactly known why birds aggregate in coordinated flocks. The most
      common hypothesis proposes that the reason is protection from predators. Most of
      the currently developed examples of individual-based predator-prey models assume
      predators are attracted to the center of a highly coordinated flock. This
      proposed attraction of a predator to a flock would appear to be contradictory to
      an alternate hypothesis that flocks evolved as a protection against predation. In
      an attempt to resolve this apparent conflict, in this article we use a fuzzy
      individual-based model to study three attack tactics (attack center, attack
      nearest, attack isolated) and analyze the success of predation on two types of
      prey (social and individualistic). Our simulations revealed that social flocking
      (as opposed to individualistic behavior) is the optimal anti-predatory response
      to predators attacking mainly isolated individuals.

PMID- 24730767
TI  - Task partitioning in a robot swarm: object retrieval as a sequence of subtasks
      with direct object transfer.
AB  - We study task partitioning in the context of swarm robotics. Task partitioning is
      the decomposition of a task into subtasks that can be tackled by different
      workers. We focus on the case in which a task is partitioned into a sequence of
      subtasks that must be executed in a certain order. This implies that the subtasks
      must interface with each other, and that the output of a subtask is used as input
      for the subtask that follows. A distinction can be made between task partitioning
      with direct transfer and with indirect transfer. We focus our study on the first
      case: The output of a subtask is directly transferred from an individual working
      on that subtask to an individual working on the subtask that follows. As a test
      bed for our study, we use a swarm of robots performing foraging. The robots have
      to harvest objects from a source, situated in an unknown location, and transport
      them to a home location. When a robot finds the source, it memorizes its position
      and uses dead reckoning to return there. Dead reckoning is appealing in robotics,
      since it is a cheap localization method and it does not require any additional
      external infrastructure. However, dead reckoning leads to errors that grow in
      time if not corrected periodically. We compare a foraging strategy that does not
      make use of task partitioning with one that does. We show that cooperation
      through task partitioning can be used to limit the effect of dead reckoning
      errors. This results in improved capability of locating the object source and in
      increased performance of the swarm. We use the implemented system as a test bed
      to study benefits and costs of task partitioning with direct transfer. We
      implement the system with real robots, demonstrating the feasibility of our
      approach in a foraging scenario.

PMID- 24730768
TI  - Intermittent animal behavior: the adjustment-deployment dilemma.
AB  - Intermittency is ubiquitous in animal behavior. We depict a coordination problem
      that is part of the more general structure of intermittent adaptation: the
      adjustment-deployment dilemma. It captures the intricate compromise between the
      time spent in adjusting a response and the time used to deploy it: The adjustment
      process improves fitness with time, but during deployment fitness of the solution
      decays as environmental conditions change. We provide a formal characterization
      of the dilemma, and solve it using computational methods. We find that the
      optimal solution always results in a high intermittency between adjustment and
      deployment around a non-maximal fitness value. Furthermore we show that this non
      maximal fitness value is directly determined by the ratio between the exponential
      coefficient of the fitness increase during adjustment and that of its decay
      coefficient during deployment. We compare the model results with experimental
      data obtained from observation and measurement of intermittent behavior in
      animals. Among other phenomena, the model is able to predict the uneven
      distribution of average duration of search and motion phases found among various
      species such as fishes, birds, and lizards. Despite the complexity of the
      problem, it can be shown to be solved by relatively simple mechanisms. We find
      that a model of a single continuous-time recurrent neuron, with the same
      parametric configuration, is capable of solving the dilemma for a wide set of
      conditions. We finally hypothesize that many of the different patterns of
      intermittent behavior found in nature might respond to optimal solutions of
      complexified versions of the adjustment-deployment dilemma under different
      constraints.

PMID- 24730769
TI  - Evaluation of the clinical characteristics and prognostic factors of
      gastrointestinal mucosa-associated lymphoid tissue (MALT) lymphoma.
AB  - BACKGROUND AND AIM: This study was undertaken to evaluate the clinical
      characteristics, prognostic factors, and long-term outcomes of patients with
      mucosa-associated lymphoid tissue (MALT) lymphoma in the gastrointestinal (GI)
      tract. METHODS: Clinical and pathological features of patients with MALT lymphoma
      in the GI tract, who were treated consecutively at Tianjin Medical University
      Cancer Institute and Hospital from 2001 to 2011, were evaluated retrospectively.
      RESULTS: Among a total of 99 identified cases, 79.79% of lymphomas were localized
      in the stomach, 20.20% in the intestinal tract, and disseminated disease was
      detected in 35.4% of cases. The estimated 5-year overall survival (OS) and 5-year
      progression-free survival (PFS) rates were 73.1% and 65.1%, respectively. The
      comparison between stomach and intestinal tract lymphomas demonstrated no
      significant difference in characteristics, but nodal involvement was
      significantly lower in gastric MALT lymphoma (26.6%) as compared with intestinal
      tract MALT lymphoma (60%, P = 0.006). The outcomes of gastric and intestinal MALT
      lymphomas were similar (OS, P = 0.492; PFS, P = 0.408), and so was the survival
      between proximal and distal gastric lymphomas (OS, P = 0.077; PFS, P = 0.181).
      Serum lactate dehydrogenase level above normal was identified as the only adverse
      prognostic factor for both OS and PFS. CONCLUSION: The clinical characteristics
      and outcomes demonstrated no significant differences between gastric and
      intestinal tract MALT lymphomas. Serum lactate dehydrogenase level was an
      independent prognostic factor for the survival of GI MALT lymphoma.

PMID- 24730771
TI  - Indicators of asthma control among students in a rural, school-based asthma
      management program.
AB  - OBJECTIVE: The evaluation sought to determine if a comprehensive, school-based
      asthma management program in a small, rural school district helped students
      improve asthma control. METHODS: To determine if students in the asthma program
      demonstrated better asthma control than students in a comparison school district,
      the evaluation team used a quasi-experimental, cross-sectional design and
      administered questionnaires assessing asthma control (which included FEV1
      measurement) to 456 students with asthma in the intervention and comparison
      districts. Data were analyzed for differences in asthma control between students
      in the two districts. To determine if students in the intervention experienced
      increased asthma control between baseline and follow-up, the evaluation team used
      a one-group retrospective design. Program records for 323 students were analyzed
      for differences in percent of predicted forced expiratory volume in one second
      (FEV1) between baseline and follow-up. RESULTS: Students with asthma in the
      intervention district exhibited significantly better asthma control than students
      with asthma in the comparison district. Percent of predicted FEV1 did not change
      significantly between baseline and follow-up for the intervention participants;
      however, post hoc analyses revealed students with poorly controlled asthma at
      baseline had significantly higher FEV1 scores at follow-up, and students with
      well-controlled asthma at baseline had significantly lower FEV1 scores at follow
      up. CONCLUSIONS: Findings suggest that the comprehensive school-based program led
      to improvements in asthma control for students with poorly controlled asthma at
      baseline, and school-based programs need mechanisms for tracking students with
      initially well-controlled asthma to ensure they maintain control.

PMID- 24730772
TI  - Asthma interventions in primary schools--a review.
AB  - OBJECTIVE: To explore, in depth, the literature for evidence supporting asthma
      interventions delivered within primary schools and to identify any "gaps" in this
      research area. METHODS: A literature search using electronic search engines (i.e.
      Medline, PubMed, Education Resources Information Center (ERIC), International
      Pharmaceutical Abstracts (IPA), Cumulative Index to Nursing and Allied Health
      Literature (CINAHL), Embase and Informit) and the search terms "asthma", "asthma
      intervention" and "school-based asthma education program" (and derivatives of
      these keywords) was conducted. RESULTS: Twenty-three articles met the inclusion
      criteria; of these eight were Randomised Controlled Trials. There was much
      variety in the type, content, delivery and outcome measures in these 23 studies.
      The most common intervention type was asthma education delivery. Most studies
      demonstrated improvement in clinical and humanistic markers, for example, asthma
      symptoms medication use (decrease in reliever medication use or decrease in the
      need for rescue oral steroid), inhaler use technique and spacer use competency,
      lung function and quality of life. Relatively few studies explored the effect of
      the intervention on academic outcomes. Most studies did not report on the
      sustainability or cost effectiveness of the intervention tested. Another drawback
      in the literature was the lack of details about the intervention and
      inconsistency in instruments selected for measuring outcomes. CONCLUSION: School
      based asthma interventions regardless of their heterogeneity have positive
      clinical, humanistic, health economical and academic outcomes.

PMID- 24730773
TI  - Oscillatory decay of the survival probability of activated diffusion across a
      limit cycle.
AB  - Activated escape of a Brownian particle from the domain of attraction of a stable
      focus over a limit cycle exhibits non-Kramers behavior: it is non-Poissonian.
      When the attractor is moved closer to the boundary, oscillations can be discerned
      in the survival probability. We show that these oscillations are due to complex
      valued higher-order eigenvalues of the Fokker-Planck operator, which we compute
      explicitly in the limit of small noise. We also show that in this limit the
      period of the oscillations is the winding number of the activated stochastic
      process. These peak probability oscillations are not related to stochastic
      resonance and should be detectable in planar dynamical systems with the topology
      described here. 

PMID- 24730770
TI  - Human epidermal growth factor receptor-2 expression in locally advanced rectal
      cancer: association with response to neoadjuvant therapy and prognosis.
AB  - The aim of this study was to determine whether pretreatment status of human
      epidermal growth factor receptor-2 (HER-2) could predict pathologic response to
      neoadjuvant chemoradiotherapy (nCRT) and outcomes for patients with locally
      advanced rectal cancer (LARC). A total of 119 patients diagnosed with LARC
      received standardized multimodal treatment. Their HER-2 status was determined in
      pretreatment biopsies by immunohistochemistry (IHC) and FISH. Tumor response was
      assessed in resected regimens using the tumor regression grade system and TNM
      staging system. Twenty-two cases in 119 patients assessed as IHC3+ or IHC2+ plus
      gene-amplified were determined as HER-2 positive. Positive HER-2 status was not
      associated with any pretreatment clinicopathologic parameters (P > 0.05). HER-2
      status could not predict pathologic response to nCRT based on downstaging (P =
      0.210) and tumor regression grade (P = 0.085) but it provides us with a trend
      that HER-2-positive tumors may be resistant to nCRT. Positive HER-2 status was
      significantly associated with poor 5-year disease-free survival (P = 0.015) and 5
      year overall survival (P = 0.026). It can act as a worse prognostic factor for
      LARC patients. 

PMID- 24730774
TI  - Anomalous diffusion in nonhomogeneous media: time-subordinated Langevin equation
      approach.
AB  - Diffusion in nonhomogeneous media is described by a dynamical process driven by a
      general Levy noise and subordinated to a random time; the subordinator depends on
      the position. This problem is approximated by a multiplicative process
      subordinated to a random time: it separately takes into account effects related
      to the medium structure and the memory. Density distributions and moments are
      derived from the solutions of the corresponding Langevin equation and compared
      with the numerical calculations for the exact problem. Both subdiffusion and
      enhanced diffusion are predicted. Distribution of the process satisfies the
      fractional Fokker-Planck equation. 

PMID- 24730775
TI  - Exit probability in inflow dynamics: nonuniversality induced by range, asymmetry,
      and fluctuation.
AB  - Probing deeper into the existing issues regarding the exit probability (EP) in
      one-dimensional dynamical models, we consider several models where the states are
      represented by Ising spins and the information flows inwards. At zero
      temperature, these systems evolve to either of two absorbing states. The EP,
      E(x), which is the probability that the system ends up with all up spins starting
      with x fraction of up spins, is found to have the general form
      E(x)=xalpha/xalpha+(1-x)alpha. The EP exponent alpha strongly depends on r, the
      range of interaction, the symmetry of the model, and the induced fluctuation.
      Even in a nearest-neighbor model, a nonlinear form of the EP can be obtained by
      controlling the fluctuations, and for the same range, different models give
      different results for alpha. Nonuniversal behavior of the EP is thus clearly
      established and the results are compared to those of existing studies in models
      with outflow dynamics to distinguish the two dynamical scenarios. 

PMID- 24730776
TI  - Transition in coupled replicas may not imply a finite-temperature ideal glass
      transition in glass-forming systems.
AB  - A key open question in the glass transition field is whether a finite temperature
      thermodynamic transition to the glass state exists or not. Recent simulations of
      coupled replicas in atomistic models have found signatures of a static transition
      as a function of replica coupling. This can be viewed as evidence of an
      associated thermodynamic glass transition in the uncoupled system. We demonstrate
      here that a different interpretation is possible. We consider the triangular
      plaquette model, an interacting spin system which displays (East model-like)
      glassy dynamics in the absence of any static transition. We show that when two
      replicas are coupled, there is a curve of equilibrium phase transitions, between
      phases of small and large overlap, in the temperature-coupling plane (located on
      the self-dual line of an exact temperature-coupling duality of the system) which
      ends at a critical point. Crucially, in the limit of vanishing coupling the
      finite temperature transition disappears, and the uncoupled system is in the
      disordered phase at all temperatures. We discuss an interpretation of atomistic
      simulations in light of this result. 

PMID- 24730777
TI  - Flexoelectricity in chiral nematic liquid crystals as a driving mechanism for the
      twist-bend and splay-bend modulated phases.
AB  - We present a continuum theoretical model describing the impact of chirality on
      nematic systems with large flexoelectricity. As opposed to achiral materials,
      where only one type of the modulated structure can exist in a given material, the
      model predicts that chirality can stabilize several modulated phases, which have
      already been observed experimentally [A. Zep et al., J. Mater. Chem. C 1, 46
      (2013)]. 

PMID- 24730778
TI  - Collaborative effects in polymer translocation and the appearance of fictitious
      free-energy barriers.
AB  - The translocation time of a polymer through a pore under the influence of an
      external field depends on a number of parameters, the most important of which are
      the field strength, the interaction with the pore, and the confinement entropy.
      Experimentally, the translocation is dominated either by the driving force
      (electrophoretic regime) or by the entropy of confinement or pore interaction
      (barrier dominated regime). In this Rapid Communication we study a simple model
      for polymer translocation, loosely based on the asymmetric exclusion process,
      which shows that it is possible to have what experimentally would be interpreted
      as barrier dominated, even where there is no barrier to translocation. This
      effective barrier is interpreted as being due to collaborative effects between
      the monomers forming the polymer chain. 

PMID- 24730779
TI  - Hub-activated signal transmission in complex networks.
AB  - A wide range of networked systems exhibit highly connected nodes (hubs) as
      prominent structural elements. The functional roles of hubs in the collective
      nonlinear dynamics of many such networks, however, are not well understood. Here,
      we propose that hubs in neural circuits may activate local signal transmission
      along sequences of specific subnetworks. Intriguingly, in contrast to previous
      suggestions of the functional roles of hubs, here, not the hubs themselves, but
      nonhub subnetworks transfer the signals. The core mechanism relies on hubs and
      nonhubs providing activating feedback to each other. It may, thus, induce the
      propagation of specific pulse and rate signals in neuronal and other
      communication networks. 

PMID- 24730780
TI  - Phenotypically heterogeneous populations in spatially heterogeneous environments.
AB  - The spatial expansion of a population in a nonuniform environment may benefit
      from phenotypic heterogeneity with interconverting subpopulations using different
      survival strategies. We analyze the crossing of an antibiotic-containing
      environment by a bacterial population consisting of rapidly growing normal cells
      and slow-growing, but antibiotic-tolerant persister cells. The dynamics of
      crossing is characterized by mean first arrival times and is found to be
      surprisingly complex. It displays three distinct regimes with different scaling
      behavior that can be understood based on an analytical approximation. Our results
      suggest that a phenotypically heterogeneous population has a fitness advantage in
      nonuniform environments and can spread more rapidly than a homogeneous
      population. 

PMID- 24730781
TI  - Three-dimensional fast magnetic reconnection driven by relativistic ultraintense
      femtosecond lasers.
AB  - Three-dimensional fast magnetic reconnection driven by two ultraintense
      femtosecond laser pulses is investigated by relativistic particle-in-cell
      simulation, where the two paralleled incident laser beams are shot into a near
      critical plasma layer to form a magnetic reconnection configuration in self
      generated magnetic fields. A reconnection X point and out-of-plane quadrupole
      field structures associated with magnetic reconnection are formed. The
      reconnection rate is found to be faster than that found in previous two
      dimensional Hall magnetohydrodynamic simulations and electrostatic turbulence
      contribution to the reconnection electric field plays an essential role. Both in
      plane and out-of-plane electron and ion accelerations up to a few MeV due to the
      magnetic reconnection process are also obtained. 

PMID- 24730782
TI  - Ultrasound-modulated bioluminescence tomography.
AB  - We propose a method to reconstruct the density of a luminescent source in a
      highly scattering medium from ultrasound-modulated optical measurements. Our
      approach is based on the solution to a hybrid inverse source problem for the
      diffusion equation. 

PMID- 24730783
TI  - Quantifying the effects of neglecting many-body interactions in coarse-grained
      models of complex fluids.
AB  - We describe a general simulation scheme for assessing the thermodynamic
      consequences of neglecting many-body effects in coarse-grained models of complex
      fluids. The method exploits the fact that the asymptote of a simple-to-measure
      structural function provides direct estimates of virial coefficients. Comparing
      the virial coefficients of an atomistically detailed system with those of a
      coarse-grained version described by pair potentials, permits the role of many
      body effects to be quantified. The approach is applied to two models: (i) a size
      asymmetrical colloid-polymer mixture, and (ii) a solution of star polymers. In
      the latter case, coarse-graining to an effective fluid described by pair
      potentials is found to neglect important aspects of the true behavior. 

PMID- 24730784
TI  - Universality and nonuniversality of mobility in heterogeneous single-file systems
      and Rouse chains.
AB  - We study analytically the tracer particle mobility in single-file systems with
      distributed friction constants. Our system serves as a prototype for
      nonequilibrium, heterogeneous, strongly interacting Brownian systems. The long
      time dynamics for such a single-file setup belongs to the same universality class
      as the Rouse model with dissimilar beads. The friction constants are drawn from a
      density rho(xi), and we derive an asymptotically exact solution for the mobility
      distribution P[MU0(s)], where MU0(s) is the Laplace-space mobility. If rho is
      light tailed (first moment exists), we find a self-averaging behavior:
      P[MU0(s)]=delta[MU0(s)-MU(s)], with MU(s)?s1/2. When rho(xi) is heavy tailed,
      rho(xi)?xi-1-alpha(0<alpha<1) for large xi, we obtain moments <[MUs(0)]n>?sbetan,
      where beta=1/(1+alpha) and there is no self-averaging. The results are
      corroborated by simulations. 

PMID- 24730785
TI  - Thermal conductivity of molecular chains with asymmetric potentials of pair
      interactions.
AB  - We provide molecular-dynamics simulation of heat transport in one-dimensional
      molecular chains with different interparticle pair potentials. We show that the
      thermal conductivity is finite in the thermodynamic limit in chains with the
      potentials that allow for bond dissociation. The Lennard-Jones, Morse, and
      Coulomb potentials are such potentials. The convergence of the thermal
      conductivity is provided by phonon scattering on the locally strongly stretched
      loose interatomic bonds at low temperature and by the many-particle scattering at
      high temperature. On the other hand, chains with a confining pair potential,
      which does not allow for bond dissociation, possess anomalous thermal
      conductivity, diverging with the chain length. We emphasize that chains with a
      symmetric or asymmetric Fermi-Pasta-Ulam potential or with combined potentials,
      containing a parabolic and/or a quartic confining potential, all exhibit
      anomalous heat transport. 

PMID- 24730786
TI  - Space-filling percolation.
AB  - A region of two-dimensional space has been filled randomly with a large number of
      growing circular disks allowing only a "slight" overlapping among them just
      before their growth stops. More specifically, each disk grows from a nucleation
      center that is selected at a random location within the uncovered region. The
      growth rate delta is a continuously tunable parameter of the problem which
      assumes a specific value while a particular pattern of disks is generated. When a
      growing disk overlaps for the first time with at least one other disk, its growth
      is stopped and is said to be frozen. In this paper we study the percolation
      properties of the set of frozen disks. Using numerical simulations we present
      evidence for the following: (i) The order parameter appears to jump
      discontinuously at a certain critical value of the area coverage; (ii) the width
      of the window of the area coverage needed to observe a macroscopic jump in the
      order parameter tends to vanish as delta->0; and on the contrary (iii) the
      cluster size distribution has a power-law-decaying functional form. While the
      first two results are the signatures of a discontinuous transition, the third
      result is indicative of a continuous transition. Therefore we refer to this
      transition as a sharp but continuous transition similar to what has been observed
      in the recently introduced Achlioptas process of explosive percolation. It is
      also observed that in the limit of delta->0, the critical area coverage at the
      transition point tends to unity, implying that the limiting pattern is space
      filling. In this limit, the fractal dimension of the pore space at the
      percolation point has been estimated to be 1.42(10) and the contact network of
      the disk assembly is found to be a scale-free network. 

PMID- 24730788
TI  - Griffiths phase and critical behavior of the two-dimensional Potts models with
      long-range correlated disorder.
AB  - The q-state Potts model with long-range correlated disorder is studied by means
      of large-scale Monte Carlo simulations for q=2, 4, 8, and 16. Evidence is given
      of the existence of a Griffiths phase, where the thermodynamic quantities display
      an algebraic finite-size scaling, in a finite range of temperatures. The critical
      exponents are shown to depend on both the temperature and the exponent of the
      algebraic decay of disorder correlations, but not on the number of states of the
      Potts model. The mechanism leading to the violation of hyperscaling relations is
      observed in the entire Griffiths phase. 

PMID- 24730787
TI  - Roles of dry friction in the fluctuating motion of an adiabatic piston.
AB  - The motion of an adiabatic piston under dry friction is investigated to clarify
      the roles of dry friction in nonequilibrium steady states. We clarify that dry
      friction can reverse the direction of the piston motion and causes a
      discontinuity or a cusplike singularity for velocity distribution functions of
      the piston. We also show that the heat fluctuation relation is modified under dry
      friction. 

PMID- 24730789
TI  - Weak commutation relations and eigenvalue statistics for products of rectangular
      random matrices.
AB  - We study the joint probability density of the eigenvalues of a product of
      rectangular real, complex, or quaternion random matrices in a unified way. The
      random matrices are distributed according to arbitrary probability densities,
      whose only restriction is the invariance under left and right multiplication by
      orthogonal, unitary, or unitary symplectic matrices, respectively. We show that a
      product of rectangular matrices is statistically equivalent to a product of
      square matrices. Hereby we prove a weak commutation relation of the random
      matrices at finite matrix sizes, which previously has been discussed for infinite
      matrix size. Moreover, we derive the joint probability densities of the
      eigenvalues. To illustrate our results, we apply them to a product of random
      matrices drawn from Ginibre ensembles and Jacobi ensembles as well as a mixed
      version thereof. For these weights, we show that the product of complex random
      matrices yields a determinantal point process, while the real and quaternion
      matrix ensembles correspond to Pfaffian point processes. Our results are
      visualized by numerical simulations. Furthermore, we present an application to a
      transport on a closed, disordered chain coupled to a particle bath. 

PMID- 24730790
TI  - Dissipation, interaction, and relative entropy.
AB  - Many thermodynamic relations involve inequalities, with equality if a process
      does not involve dissipation. In this article we provide equalities in which the
      dissipative contribution is shown to involve the relative entropy (also called
      the Kullback-Leibler divergence). The processes considered are general time
      evolutions in both classical and quantum mechanics, and the initial state is
      sometimes thermal, sometimes partially so. As an application, the relative
      entropy is related to transport coefficients. 

PMID- 24730791
TI  - Distribution of dynamical quantities in the contact process, random walks, and
      quantum spin chains in random environments.
AB  - We study the distribution of dynamical quantities in various one-dimensional
      disordered models, the critical behavior of which is described by an infinite
      randomness fixed point. In the disordered contact process, the survival
      probability P(t) is found to show multiscaling in the critical point, meaning
      that P(t)=t-delta, where the (environment and time-dependent) exponent delta has
      a universal limit distribution when t->infinity. The limit distribution is
      determined by the strong disorder renormalization group method analytically in
      the end point of a semi-infinite lattice, where it is found to be exponential,
      while, in the infinite system, conjectures on its limiting behaviors for small
      and large delta, which are based on numerical results, are formulated. By the
      same method, the survival probability in the problem of random walks in random
      environments is also shown to exhibit multiscaling with an exponential limit
      distribution. In addition to this, the (imaginary-time) spin-spin autocorrelation
      function of the random transverse-field Ising chain is found to have a form
      similar to that of survival probability of the contact process at the level of
      the renormalization approach. Consequently, a relationship between the
      corresponding limit distributions in the two problems can be established.
      Finally, the distribution of the spontaneous magnetization in this model is also
      discussed. 

PMID- 24730792
TI  - Rare-event trajectory ensemble analysis reveals metastable dynamical phases in
      lattice proteins.
AB  - We explore the dynamical large deviations of a lattice heteropolymer model of a
      protein by means of path sampling of trajectories. We uncover the existence of
      nonequilibrium dynamical phase transitions in ensembles of trajectories between
      active and inactive dynamical phases, whose nature depends on the properties of
      the interaction potential. We consider three potentials: two heterogeneous
      interaction potentials and a homogeneous Go potential. When preserving the full
      heterogeneity of interactions due to a given amino acid sequence, either in a
      fully interacting model or in a native contacts interacting model (heterogeneous
      Go model), the observed dynamic transitions occur between equilibrium highly
      native states and highly native but kinetically trapped states. A native activity
      is defined that allows us to distinguish these dynamic phases. In contrast, for
      the homogeneous Go model, where all native interaction energies are uniform and
      the amino acid sequence plays no role, the dynamical transition is a direct
      consequence of the static bistability between the unfolded and the native state.
      In the two heterogeneous interaction models the native-active and native-inactive
      states, despite their thermodynamic similarity, have widely varying dynamical
      properties, and the transition between them occurs even in lattice proteins whose
      sequences are designed to make them optimal folders. 

PMID- 24730793
TI  - Critical behavior of a relativistic Bose gas.
AB  - We show that the thermodynamic behavior of relativistic ideal Bose gas, recently
      studied numerically by Grether et al., can be obtained analytically. Using the
      analytical results, we obtain the critical behavior of the relativistic Bose gas
      exactly for all the regimes. We show that these analytical results reduce to
      those of Grether et al. in different regimes of the Bose gas. Furthermore, we
      also obtain an analytically closed-form expression for the energy density for the
      Bose gas that is valid in all regimes. 

PMID- 24730794
TI  - Static and dynamical properties of a hard-disk fluid confined to a narrow
      channel.
AB  - The thermodynamic properties of disks moving in a channel sufficiently narrow
      that they can collide only with their nearest neighbors can be solved exactly by
      determining the eigenvalues and eigenfunctions of an integral equation. Using it,
      we have determined the correlation length xi of this system. We have developed an
      approximate solution which becomes exact in the high-density limit. It describes
      the system in terms of defects in the regular zigzag arrangement of disks found
      in the high-density limit. The correlation length is then effectively the spacing
      between the defects. The time scales for defect creation and annihilation are
      determined with the help of transition-state theory, as is the diffusion
      coefficient of the defects, and these results are found to be in good agreement
      with molecular dynamics simulations. On compressing the system with the
      Lubachevsky-Stillinger procedure, jammed states are obtained whose packing
      fractions phiJ are a function of the compression rate gamma. We find a
      quantitative explanation of this dependence by making use of the Kibble-Zurek
      hypothesis. We have also determined the point-to-set length scale xiPS for this
      system. At a packing fraction phi close to its largest value phimax, xiPS has a
      simple power law divergence, xiPS~1/(1-phi/phimax), while xi diverges much
      faster, ln(xi)~1/(1-phi/phimax). 

PMID- 24730795
TI  - Improved predictions of rare events using the Crooks fluctuation theorem.
AB  - This article explores the applicability of concepts from nonequilibrium
      thermodynamics to rare event prediction. The Crooks fluctuation theorem is an
      equality constraint on the probability distribution of a thermodynamical
      observable. We consider as a prediction target the exceedance of a threshold of
      such an observable, where the magnitude of the threshold modulates the rareness
      of the event. A probability forecast is constructed for this event based on a
      small observational data set. A simple method is proposed that exploits the
      Crooks fluctuation theorem to estimate this probability. It is shown that this
      estimator has improved predictive skill compared to the relative frequency of
      exceedance in the data set. We quantify this improvement in two examples, and
      study its dependence on the threshold magnitude and sample size in different
      systems. Further improvements are achieved by combining the Crooks estimator with
      the frequency estimator. 

PMID- 24730796
TI  - Crossover behavior of conductivity in a discontinuous percolation model.
AB  - When conducting bonds are occupied randomly in a two-dimensional square lattice,
      the conductivity of the system increases continuously as the density of those
      conducting bonds exceeds the percolation threshold. Such a behavior is well known
      in percolation theory; however, the conductivity behavior has not been studied
      yet when the percolation transition is discontinuous. Here we investigate the
      conductivity behavior through a discontinuous percolation model evolving under a
      suppressive external bias. Using effective medium theory, we analytically
      calculate the conductivity behavior as a function of the density of conducting
      bonds. The conductivity function exhibits a crossover behavior from a drastically
      to a smoothly increasing function beyond the percolation threshold in the
      thermodynamic limit. The analytic expression fits well our simulation data. 

PMID- 24730797
TI  - Quantum fluctuation theorems and generalized measurements during the force
      protocol.
AB  - Generalized measurements of an observable performed on a quantum system during a
      force protocol are investigated and conditions that guarantee the validity of the
      Jarzynski equality and the Crooks relation are formulated. In agreement with
      previous studies by M. Campisi, P. Talkner, and P. Hanggi [Phys. Rev. Lett. 105,
      140601 (2010); Phys. Rev. E 83, 041114 (2011)], we find that these fluctuation
      relations are satisfied for projective measurements; however, for generalized
      measurements special conditions on the operators determining the measurements
      need to be met. For the Jarzynski equality to hold, the measurement operators of
      the forward protocol must be normalized in a particular way. The Crooks relation
      additionally entails that the backward and forward measurement operators depend
      on each other. Yet, quite some freedom is left as to how the two sets of
      operators are interrelated. This ambiguity is removed if one considers selective
      measurements, which are specified by a joint probability density function of work
      and measurement results of the considered observable. We find that the respective
      forward and backward joint probabilities satisfy the Crooks relation only if the
      measurement operators of the forward and backward protocols are the time-reversed
      adjoints of each other. In this case, the work probability density function
      conditioned on the measurement result satisfies a modified Crooks relation. The
      modification appears as a protocol-dependent factor that can be expressed by the
      information gained by the measurements during the forward and backward protocols.
      Finally, detailed fluctuation theorems with an arbitrary number of intervening
      measurements are obtained. 

PMID- 24730798
TI  - Entanglement enhances cooling in microscopic quantum refrigerators.
AB  - Small self-contained quantum thermal machines function without external source of
      work or control but using only incoherent interactions with thermal baths. Here
      we investigate the role of entanglement in a small self-contained quantum
      refrigerator. We first show that entanglement is detrimental as far as efficiency
      is concerned-fridges operating at efficiencies close to the Carnot limit do not
      feature any entanglement. Moving away from the Carnot regime, we show that
      entanglement can enhance cooling and energy transport. Hence, a truly quantum
      refrigerator can outperform a classical one. Furthermore, the amount of
      entanglement alone quantifies the enhancement in cooling. 

PMID- 24730799
TI  - Dynamics and physical interpretation of quasistationary states in systems with
      long-range interactions.
AB  - The time evolution of the one-particle distribution function of an N-particle
      classical Hamiltonian system with long-range interactions satisfies the Vlasov
      equation in the limit of infinite N. In this paper we present a new derivation of
      this result using a different approach allowing a discussion of the role of
      interparticle correlations on the system dynamics. Otherwise for finite N
      collisional corrections must be introduced. This has allowed a quite
      comprehensive study of the quasistationary states (QSSs) though many aspects of
      the physical interpretations of these states still remain unclear. In this paper
      a proper definition of time scale for long time evolution is discussed, and
      several numerical results are presented for different values of N. Previous
      reports indicate that the lifetimes of the QSS scale as N1.7 or even the system
      properties scale with exp(N). However, preliminary results presented here
      indicates that time scale goes as N2 for a different type of initial condition.
      We also discuss how the form of the interparticle potential determines the
      convergence of the N-particle dynamics to the Vlasov equation. The results are
      obtained in the context of the following models: the Hamiltonian mean field, the
      Self-gravitating ring model, and one- and two-dimensional systems of gravitating
      particles. We have also provided information of the validity of the Vlasov
      equation for finite N. 

PMID- 24730800
TI  - Relaxation of the thermal Casimir force between net neutral plates containing
      Brownian charges.
AB  - We investigate the dynamics of thermal Casimir interactions between plates
      described within a living conductor model, with embedded mobile anions and
      cations, whose density field obeys a stochastic partial differential equation
      which can be derived starting from the Langevin equations of the individual
      particles. This model describes the thermal Casimir interaction in the same way
      that the fluctuating dipole model describes van der Waals interactions. The model
      is analytically solved in a Debye-Huckel-like approximation. We identify several
      limiting dynamical regimes where the time dependence of the thermal Casimir
      interactions can be obtained explicitly. Most notably we find a regime with
      diffusive scaling, even though the charges are confined to the plates and do not
      diffuse into the intervening space, which makes the diffusive scaling difficult
      to anticipate and quite unexpected on physical grounds. 

PMID- 24730801
TI  - High-resolution Monte Carlo study of the multicritical point in the three
      dimensional XXZ Heisenberg antiferromagnet.
AB  - We use Monte Carlo simulations to study the XXZ Heisenberg antiferromagnet in a
      field in order to clearly determine the nature of the multicritical point. We use
      a hybrid sampling method with Metropolis and Wolff-cluster algorithms, along with
      histogram reweighting techniques. Staggered magnetization susceptibilities,
      Binder cumulants, and finite-size scaling are considered in an effort to detect a
      possible biconical phase. An analysis of the probability distribution of the
      magnetization allowed us to conclude that the multicritical point is bicritical
      and it is in the three-dimensional Heisenberg universality class. 

PMID- 24730802
TI  - Green-Kubo relation for friction at liquid-solid interfaces.
AB  - We have developed a Green-Kubo relation that enables accurate calculations of
      friction at solid-liquid interfaces directly from equilibrium molecular dynamics
      (MD) simulations and that provides a pathway to bypass the time-scale limitations
      of typical nonequilibrium MD simulations. The theory has been validated for a
      number of different interfaces and it is demonstrated that the liquid-solid slip
      is an intrinsic property of an interface. Because of the high numerical
      efficiency of our method, it can be used in the design of interfaces for
      applications in aqueous environments, such as nano- and microfluidics. 

PMID- 24730803
TI  - Complexity and instability of quantum motion near a quantum phase transition.
AB  - We show that the number of harmonics of the Wigner function, recently proposed as
      a measure of quantum complexity, can also be used to characterize quantum phase
      transitions. The nonanalytic behavior of this quantity in the neighborhood of a
      quantum phase transition is illustrated by means of the Dicke model and is
      compared to two well-known measures of the (in)stability of quantum motion: the
      quantum Loschmidt echo and fidelity. 

PMID- 24730804
TI  - Composition distributions of particles in a gelling mixture.
AB  - Gelation in a two component disperse system wherein binary coagulation governs
      the temporal changes of particle composition spectra is studied for the
      crossproduct coagulation kernel proportional to m1n2+m2n1, with m,n being the
      numbers of monomers of the first and the second component in the coalescing pair
      of particles. This model reveals the sol-gel transition, i.e., after a finite
      interval of time the conservation of the total particle mass concentration
      violates because of the formation of giant particles (the gel). This paper
      reports on the exact solution of this model for arbitrary initial particle
      composition spectra. Exact expressions for the particle composition spectrum, the
      gel mass, and the second moments of the composition distribution are derived. Two
      scenarios of gelation, where the gel is either active or passive, are considered.

PMID- 24730805
TI  - Bending rigidity and higher-order curvature terms for the hard-sphere fluid near
      a curved wall.
AB  - In this work I derive analytic expressions for the curvature-dependent fluid
      substrate surface tension of a hard-sphere fluid on a hard curved wall. In the
      first step, the curvature thermodynamic properties are found as truncated power
      series in the activity in terms of the exactly known second- and third-order
      cluster integrals of the hard-sphere fluid near spherical and cylindrical walls.
      These results are then expressed as packing fraction power series and transformed
      to different reference regions, which is equivalent to considering different
      positions of the dividing surface. Based on the truncated series it is shown that
      the bending rigidity of the system is non-null and that higher-order terms in the
      curvature also exist. In the second step, approximate analytic expressions for
      the surface tension, the Tolman length, the bending rigidity, and the Gaussian
      rigidity as functions of the packing fraction are found by considering the known
      terms of the series expansion complemented with a simple fitting approach. It is
      found that the obtained formulas accurately describe the curvature thermodynamic
      properties of the system; further, they are more accurate than any previously
      published expressions. 

PMID- 24730806
TI  - Solution of the antiferromagnetic Ising model on a tetrahedron recursive lattice.
AB  - We consider the antiferromagnetic spin-1/2 Ising model on the recursive
      tetrahedron lattice on which two elementary tetrahedrons are connected at each
      site. The model represents the simplest approximation of the antiferromagnetic
      Ising model on the real three-dimensional tetrahedron lattice which takes into
      account effects of frustration. An exact analytical solution of the model is
      found and discussed. It is shown that the model exhibits neither the first-order
      nor the second-order phase transitions. A detailed analysis of the magnetization
      of the model in the presence of the external magnetic field is performed and the
      existence of the magnetization plateaus for low temperatures is shown. All
      possible ground states of the model are found and discussed. The existence of
      nontrivial singular ground states is proven and exact explicit expressions for
      them are found. 

PMID- 24730807
TI  - Scaling of temperature dependence of charge mobility in molecular Holstein
      chains.
AB  - The temperature dependence of a charge mobility in a model DNA based on a
      Holstein Hamiltonian is calculated for four types of homogeneous sequences It has
      turned out that upon rescaling all four types are quite similar. Two types of
      rescaling, i.e., those for low and intermediate temperatures, are found. The
      curves obtained are approximated on a logarithmic scale by cubic polynomials. We
      believe that for model homogeneous biopolymers with parameters close to the
      designed ones, one can assess the value of the charge mobility without carrying
      out resource-intensive direct simulation, just by using a suitable approximating
      function. 

PMID- 24730808
TI  - Asymmetric simple exclusion process on chains with a shortcut.
AB  - We consider the asymmetric simple exclusion process (TASEP) on an open network
      consisting of three consecutively coupled macroscopic chain segments with a
      shortcut between the tail of the first segment and the head of the third one. The
      model was introduced by Y.-M. Yuan et al. [J. Phys. A 40, 12351 (2007)] to
      describe directed motion of molecular motors along twisted filaments. We report
      here unexpected results which revise the previous findings in the case of maximum
      current through the network. Our theoretical analysis, based on the effective
      rates' approximation, shows that the second (shunted) segment can exist in both
      low- and high-density phases, as well as in the coexistence (shock) phase.
      Numerical simulations demonstrate that the last option takes place in finite-size
      networks with head and tail chains of equal length, provided the injection and
      ejection rates at their external ends are equal and greater than one-half. Then
      the local density distribution and the nearest-neighbor correlations in the
      middle chain correspond to a shock phase with completely delocalized domain wall.
      Upon moving the shortcut to the head or tail of the network, the density profile
      takes a shape typical of a high- or low-density phase, respectively.
      Surprisingly, the main quantitative parameters of that shock phase are governed
      by a positive root of a cubic equation, the coefficients of which linearly depend
      on the probability of choosing the shortcut. Alternatively, they can be expressed
      in a universal way through the shortcut current. The unexpected conclusion is
      that a shortcut in the bulk of a single lane may create traffic jams. 

PMID- 24730809
TI  - Dynamic transition of supercritical hydrogen: defining the boundary between
      interior and atmosphere in gas giants.
AB  - Understanding the physics of gas giants requires knowledge about the behavior of
      hydrogen at extreme pressures and temperatures. Molecular hydrogen in these
      planets is supercritical, and has been considered as a physically homogeneous
      state where no differences can be made between a liquid and a gas and where all
      properties undergo no marked or distinct changes with pressure and temperature,
      the picture believed to hold below the dissociation and metallization transition.
      Here, we show that in Jupiter and Saturn, supercritical molecular hydrogen
      undergoes a dynamic transition around 10 GPa and 3000 K from the "rigid" liquid
      state to the "nonrigid" gas-like fluid state at the Frenkel line recently
      proposed, with the accompanying qualitative changes of all major physical
      properties. The consequences of this finding are discussed, including a
      physically justified way to demarcate the interior and the atmosphere in gas
      giants. 

PMID- 24730810
TI  - Spatial correlation functions and dynamical exponents in very large samples of
      four-dimensional spin glasses.
AB  - The study of the low temperature phase of spin glass models by means of Monte
      Carlo simulations is a challenging task, because of the very slow dynamics and
      the severe finite-size effects they show. By exploiting at the best the
      capabilities of standard modern CPUs (especially the streaming single
      instruction, multiple data extensions), we have been able to simulate the four
      dimensional Edwards-Anderson model with Gaussian couplings up to sizes L=70 and
      for times long enough to accurately measure the asymptotic behavior. By quenching
      systems of different sizes to the critical temperature and to temperatures in the
      whole low temperature phase, we have been able to identify the regime where
      finite-size effects are negligible: xi(t)?L/7. Our estimates for the dynamical
      exponent (z?1/T) and for the replicon exponent (alpha?1.0 and T independent),
      that controls the decay of the spatial correlation in the zero overlap sector,
      are consistent with the replica symmetry breaking theory, but the latter differs
      from the theoretically conjectured value. 

PMID- 24730811
TI  - Satisfiability-unsatisfiability transition in the adversarial satisfiability
      problem.
AB  - Adversarial satisfiability (AdSAT) is a generalization of the satisfiability
      (SAT) problem in which two players try to make a Boolean formula true (resp.
      false) by controlling their respective sets of variables. AdSAT belongs to a
      higher complexity class in the polynomial hierarchy than SAT, and therefore the
      nature of the critical region and the transition are not easily parallel to those
      of SAT and worthy of independent study. AdSAT also provides an upper bound for
      the transition threshold of the quantum satisfiability problem (QSAT). We present
      a complete algorithm for AdSAT, show that 2-AdSAT is in P, and then study two
      stochastic algorithms (simulated annealing and its improved variant) and compare
      their performances in detail for 3-AdSAT. Varying the density of clauses alpha we
      claim that there is a sharp SAT-UNSAT transition at a critical value whose upper
      bound is alphac?1.5, suggesting a much stricter upper bound for the QSAT
      transition than those previously found. 

PMID- 24730812
TI  - Temperature chaos and quenched heterogeneities.
AB  - We present a treatable generalization of the Sherrington-Kirkpatrick (SK) model
      which introduces correlations in the elements of the coupling matrix through
      multiplicative disorder on the single variables and investigate the consequences
      on the phase diagram. We define a generalized qEA parameter and test the
      structural stability of the SK results in this correlated case evaluating the de
      Almeida-Thouless line of the model. As a main result we demonstrate the increase
      of temperature chaos effects due to heterogeneities. 

PMID- 24730813
TI  - Entropic memory erasure.
AB  - We have considered a Brownian particle confined in a two-dimensional bilobal
      enclosure where the state of the particle represents a bit of information having
      binary value 0 (left lobe) or 1 (right lobe). A time linear force is applied on
      the particle, driving it selectively to a particular lobe, and thus erasing one
      bit of information. We explore the statistics of heat and work associated with
      memory erasure to realize the Landauer limit in the entropic domain. Our results
      suggest that the mean value of work done associated with the complete erasure
      procedure satisfies the Landauer bound even when the memory is purely entropic in
      nature. 

PMID- 24730814
TI  - Non-mean-field critical exponent in a mean-field model: dynamics versus
      statistical mechanics.
AB  - Mean-field theory tells us that the classical critical exponent of susceptibility
      is twice that of magnetization. However, linear response theory based on the
      Vlasov equation, which is naturally introduced by the mean-field nature, makes
      the former exponent half of the latter for families of quasistationary states
      having second order phase transitions in the Hamiltonian mean-field model and its
      variances, in the low-energy phase. We clarify that this strange exponent is due
      to the existence of Casimir invariants which trap the system in a quasistationary
      state for a time scale diverging with the system size. The theoretical prediction
      is numerically confirmed by N-body simulations for the equilibrium states and a
      family of quasistationary states. 

PMID- 24730815
TI  - Ensemble renormalization group for the random-field hierarchical model.
AB  - The renormalization group (RG) methods are still far from being completely
      understood in quenched disordered systems. In order to gain insight into the
      nature of the phase transition of these systems, it is common to investigate
      simple models. In this work we study a real-space RG transformation on the Dyson
      hierarchical lattice with a random field, which leads to a reconstruction of the
      RG flow and to an evaluation of the critical exponents of the model at T=0. We
      show that this method gives very accurate estimations of the critical exponents
      by comparing our results with those obtained by some of us using an independent
      method. 

PMID- 24730816
TI  - Globally synchronized oscillations in complex cyclic games.
AB  - The rock-paper-scissors game and its generalizations with S>3 species are well
      studied models for cyclically interacting populations. Four is, however, the
      minimum number of species that, by allowing other interactions beyond the single,
      cyclic loop, breaks both the full intransitivity of the food graph and the one
      predator, one-prey symmetry. Lutz et al. [J. Theor. Biol. 317, 286 (2013)] have
      shown the existence, on a square lattice, of two distinct phases, with either
      four or three coexisting species. In both phases, each agent is eventually
      replaced by one of its predators, but these strategy oscillations remain
      localized as long as the interactions are short ranged. Distant regions may be
      either out of phase or cycling through different food-web subloops (if any). Here
      we show that upon replacing a minimum fraction Q of the short-range interactions
      by long-range ones, there is a Hopf bifurcation, and global oscillations become
      stable. Surprisingly, to build such long-distance, global synchronization, the
      four-species coexistence phase requires fewer long-range interactions than the
      three-species phase, while one would naively expect the opposite to be true.
      Moreover, deviations from highly homogeneous conditions (chi=0 or 1) increase Qc,
      and the more heterogeneous is the food web, the harder the synchronization is. By
      further increasing Q, while the three-species phase remains stable, the four
      species one has a transition to an absorbing, single-species state. The existence
      of a phase with global oscillations for S>3, when the interaction graph has
      multiple subloops and several possible local cycles, leads to the conjecture that
      global oscillations are a general characteristic, even for large, realistic food
      webs. 

PMID- 24730817
TI  - Inconsistencies in steady-state thermodynamics.
AB  - We address the issue of extending thermodynamics to nonequilibrium steady states.
      Using driven stochastic lattice gases, we ask whether consistent definitions of
      an effective chemical potential MU, and an effective temperature Te, are
      possible. MU and Te are determined via coexistence, i.e., zero flux of particles
      and energy between the driven system and a reservoir. In the lattice gas with
      nearest-neighbor exclusion, temperature is not relevant, and we find that the
      effective chemical potential, a function of density and drive strength, satisfies
      the zeroth law, and correctly predicts the densities of coexisting systems. In
      the Katz-Lebowitz-Spohn driven lattice gas both MU and Te need to be defined. We
      show analytically that in this case the zeroth law is violated for Metropolis
      exchange rates, and determine the size of the violations numerically. The zeroth
      law appears to be violated for generic exchange rates. Remarkably, the system
      reservoir coupling proposed by Sasa and Tasaki [J. Stat. Phys. 125, 125 (2006)]
      is free of inconsistencies, and the zeroth law holds. This is because the rate
      depends only on the state of the donor system, and is independent of that of the
      acceptor. 

PMID- 24730818
TI  - Pros and cons of swimming in a noisy environment.
AB  - The problem of optimal microscopic swimming in a noisy environment is analyzed. A
      simplified model in which propulsion is generated by the relative motion of three
      spheres connected by immaterial links has been considered. We show that an
      optimized noisy microswimmer requires less power for propulsion (on average) than
      an optimal noiseless counterpart migrating with identical mean velocity and
      swimming stroke amplitude. We also show that noise can be used to overcome some
      of the limitations of the scallop theorem and have a swimmer that is able to
      propel itself with control over just one degree of freedom. 

PMID- 24730819
TI  - Stochastic resonance in the two-dimensional q-state clock models.
AB  - We numerically study stochastic resonance in the two-dimensional q-state clock
      models from q=2 to 7 under a weak oscillating magnetic field. As in the mean
      field case, we observe double resonance peaks, but the detailed response strongly
      depends on the direction of the field modulation for q>=5 where the quasiliquid
      phase emerges. We explain this behavior in terms of free-energy landscapes on the
      two-dimensional magnetization plane. 

PMID- 24730820
TI  - Event-triggered feedback in noise-driven phase oscillators.
AB  - Using a stochastic nonlinear phase oscillator model, we study the effect of event
      triggered feedback on the statistics of interevent intervals. Events are
      associated with the entering of a new cycle. The feedback is modeled by an
      instantaneous increase (positive feedback) or decrease (negative feedback) of the
      oscillator frequency whenever an event occurs followed by an exponential decay on
      a slow time scale. In addition to the known excitable and oscillatory regimes,
      which are separated by a saddle node on invariant circle bifurcation, positive
      feedback can lead to bistable dynamics and a change of the system's excitability.
      The feedback has also a strong effect on noise-induced phenomena like coherence
      resonance or anticoherence resonance. Both positive and negative feedback can
      lead to more regular output for particular noise strengths. Finally, we
      investigate serial correlations in the sequence of interevent intervals that
      occur due to the additional slow dynamics. We derive approximations for the
      serial correlation coefficient and show that positive feedback results in
      extended positive interval correlations, whereas negative feedback yields short
      ranging negative correlations. Investigating the interplay of feedback and the
      nonlinear phase dynamics close to the bifurcation, we find that correlations are
      most pronounced for optimal feedback strengths. 

PMID- 24730821
TI  - Random transitions described by the stochastic Smoluchowski-Poisson system and by
      the stochastic Keller-Segel model.
AB  - We study random transitions between two metastable states that appear below a
      critical temperature in a one-dimensional self-gravitating Brownian gas with a
      modified Poisson equation experiencing a second order phase transition from a
      homogeneous phase to an inhomogeneous phase [P. H. Chavanis and L. Delfini, Phys.
      Rev. E 81, 051103 (2010)]. We numerically solve the N-body Langevin equations and
      the stochastic Smoluchowski-Poisson system, which takes fluctuations (finite N
      effects) into account. The system switches back and forth between the two
      metastable states (bistability) and the particles accumulate successively at the
      center or at the boundary of the domain. We explicitly show that these random
      transitions exhibit the phenomenology of the ordinary Kramers problem for a
      Brownian particle in a double-well potential. The distribution of the residence
      time is Poissonian and the average lifetime of a metastable state is given by the
      Arrhenius law; i.e., it is proportional to the exponential of the barrier of free
      energy DeltaF divided by the energy of thermal excitation kBT. Since the free
      energy is proportional to the number of particles N for a system with long-range
      interactions, the lifetime of metastable states scales as eN and is considerable
      for N?1. As a result, in many applications, metastable states of systems with
      long-range interactions can be considered as stable states. However, for moderate
      values of N, or close to a critical point, the lifetime of the metastable states
      is reduced since the barrier of free energy decreases. In that case, the
      fluctuations become important and the mean field approximation is no more valid.
      This is the situation considered in this paper. By an appropriate change of
      notations, our results also apply to bacterial populations experiencing
      chemotaxis in biology. Their dynamics can be described by a stochastic Keller
      Segel model that takes fluctuations into account and goes beyond the usual mean
      field approximation. 

PMID- 24730822
TI  - Dynamical transition in the D=3 Edwards-Anderson spin glass in an external
      magnetic field.
AB  - We study the off-equilibrium dynamics of the three-dimensional Ising spin glass
      in the presence of an external magnetic field. We have performed simulations both
      at fixed temperature and with an annealing protocol. Thanks to the Janus special
      purpose computer, based on field-programmable gate array (FPGAs), we have been
      able to reach times equivalent to 0.01 s in experiments. We have studied the
      system relaxation both for high and for low temperatures, clearly identifying a
      dynamical transition point. This dynamical temperature is strictly positive and
      depends on the external applied magnetic field. We discuss different
      possibilities for the underlying physics, which include a thermodynamical spin
      glass transition, a mode-coupling crossover, or an interpretation reminiscent of
      the random first-order picture of structural glasses. 

PMID- 24730823
TI  - Fast-mode elimination in stochastic metapopulation models.
AB  - We investigate the stochastic dynamics of entities which are confined to a set of
      islands, between which they migrate. They are assumed to be one of two types, and
      in addition to migration, they also reproduce and die. Birth and death events are
      later moderated by weak selection. Systems which fall into this class are common
      in biology and social science, occurring in ecology, population genetics,
      epidemiology, biochemistry, linguistics, opinion dynamics, and other areas. In
      all these cases the governing equations are intractable, consisting as they do of
      multidimensional Fokker-Planck equations or, equivalently, coupled nonlinear
      stochastic differential equations with multiplicative noise. We develop a
      methodology which exploits a separation in time scales between fast and slow
      variables to reduce these equations so that they resemble those for a single
      island, which are amenable to analysis. The technique is generally applicable,
      but we choose to discuss it in the context of population genetics, in part
      because of the extra features that appear due to selection. The idea behind the
      method is simple, its application is systematic, and the results are in very good
      agreement with simulations of the full model for a range of parameter values. 

PMID- 24730824
TI  - Information pathways in a disordered lattice.
AB  - The maximum entropy random walk in a disordered lattice is obtained as a
      consequence of the principle of maximum entropy for a particular type of prior
      information without restriction on the number of steps. This novel result
      demonstrates that transition probabilities defining the random walk represent a
      general characterization of information on a defective lattice and does not
      necessarily reflect a physical process. The localization phenomenon is shown to
      be a consequence of solution of the Laplacian on the lattice-hence it contradicts
      the previous interpretation as a spherical Lifshitz state-and naturally
      generalizes to multiple modes, whose order reflects the significance of
      information. The dynamics of information flow on the microscale is related to the
      macroscopic structure of the lattice through a Fokker-Planck formalism. This
      newly derived theoretical framework is opening doors for a wide range of
      applications in analysis of (information) flow in disordered systems. That
      includes potentially breakthrough resolution of the outstanding problem of
      inferring connectivity from discrete imaging (i.e., neural) data. 

PMID- 24730825
TI  - Critical behavior of a quantum chain with four-spin interactions in the presence
      of longitudinal and transverse magnetic fields.
AB  - We study the ground-state properties of a spin-1/2 model on a chain containing
      four-spin Ising-like interactions in the presence of both transverse and
      longitudinal magnetic fields. We use entanglement entropy and finite-size scaling
      methods to obtain the phase diagrams of the model. Our numerical calculations
      reveal a rich variety of phases and the existence of multicritical points in the
      system. We identify phases with both ferromagnetic and antiferromagnetic
      orderings. We also find periodically modulated orderings formed by a cluster of
      like spins followed by another cluster of opposite like spins. The quantum phases
      in the model are found to be separated by either first- or second-order
      transition lines. 

PMID- 24730826
TI  - Coarsening modes of clusters of aggregating particles.
AB  - There are two modes by which clusters of aggregating particles can coalesce: The
      clusters can merge either (i) by the Ostwald ripening process, in which particles
      diffuse from one cluster to the other while the cluster centers remain
      stationary, or (ii) by means of a cluster translation mode, in which the clusters
      move toward each other and join. To understand in detail the interplay between
      these different modes, we study a model system of hard particles with an
      additional attraction between them. The particles diffuse along narrow channels
      with smooth or periodically corrugated walls, so that the system may be treated
      as one-dimensional. When the attraction between the particles is strong enough,
      they aggregate to form clusters. The channel potential influences whether
      clusters can move easily or not through the system and can prevent cluster
      motion. We use dynamical density functional theory to study the dynamics of the
      aggregation process, focusing in particular on the coalescence of two equal-sized
      clusters. As long as the particle hard-core diameter is nonzero, we find that the
      coalescence process can be halted by a sufficiently strong corrugation potential.
      The period of the potential determines the size of the final stable clusters. For
      the case of smooth channel walls, we demonstrate that there is a crossover in the
      dominance of the two different coarsening modes, which depends on the strength of
      the attraction between particles, the cluster sizes, and the separation distance
      between clusters. 

PMID- 24730827
TI  - Classical scattering in strongly attractive potentials.
AB  - Scattering in central attractive potentials is investigated systematically, in
      the limit of strong interaction, when large-angle scattering dominates. In
      particular, three important model interactions (Lennard-Jones, Yukawa, and
      exponential), which are qualitatively different from each other, are studied in
      detail. It is shown that for each of these interactions the dependence of the
      scattering angle on the properly normalized impact parameter exhibits a
      quasiuniversal behavior. This implies simple scaling of the transport cross
      sections with energy in the considered limit. Accurate fits for the momentum
      transfer cross section are suggested. Applications of the obtained results are
      discussed. 

PMID- 24730828
TI  - Aging of the (2+1)-dimensional Kardar-Parisi-Zhang model.
AB  - Extended dynamical simulations have been performed on a (2+1)-dimensional driven
      dimer lattice-gas model to estimate aging properties. The autocorrelation and the
      autoresponse functions are determined and the corresponding scaling exponents are
      tabulated. Since this model can be mapped onto the (2+1)-dimensional Kardar
      Parisi-Zhang surface growth model, our results contribute to the understanding of
      the universality class of that basic system. 

PMID- 24730829
TI  - Lattice statistical theory of random walks on a fractal-like geometry.
AB  - We have designed a two-dimensional, fractal-like lattice and explored, both
      numerically and analytically, the differences between random walks on this
      lattice and a regular, square-planar Euclidean lattice. We study the efficiency
      of diffusion-controlled processes for flows from external sites to a
      centrosymmetric reaction center and, conversely, for flows from a centrosymmetric
      source to boundary sites. In both cases, we find that analytic expressions
      derived for the mean walk length on the fractal-like lattice have an algebraic
      dependence on system size, whereas for regular Euclidean lattices the dependence
      can be transcendental. These expressions are compared with those derived in the
      continuum limit using classical diffusion theory. Our analysis and the numerical
      results quantify the extent to which one paradigmatic class of spatial
      inhomogeneities can compromise the efficiency of adatom diffusion on solid
      supports and of surface-assisted self-assembly in metal-organic materials. 

PMID- 24730830
TI  - Nonequilibrium entropic temperature and its lower bound for quantum stochastic
      processes.
AB  - In this paper, we have studied the Shannon "entropic" nonequilibrium temperature
      (NET) of quantum Brownian systems. The Brownian particle is attached to either a
      bosonic or fermionic bath. Based on the Fokker-Planck description of the c-number
      quantum Langevin equation, we have calculated entropy production, NET, and their
      bounds. Entropy production (EP), the upper bound of entropy production (UBEP),
      and the deviation of the UBEP from EP monotonically decrease as functions of time
      to equilibrium value for both of the thermal baths. The deviation decreases with
      increase of temperature of the bosonic thermal bath, but it becomes larger as the
      temperature of the fermionic bath grows. We also observe that nonequilibrium
      temperature and its lower bound monotonically increase to equilibrium value with
      the progression of time. But their difference as a function of time shows an
      optimum behavior in most cases. Finally, we have observed that at long time, the
      entropic temperature (for a bosonic thermal bath) first increases nonlinearly as
      a function of thermodynamic temperature (TT) and, if the TT is appreciably large,
      then it grows linearly. But for the fermionic thermal bath, the entropic
      temperature decreases monotonically as a nonlinear function of thermodynamic
      temperature to zero value. 

PMID- 24730831
TI  - Experimental investigation into the impact of a liquid droplet onto a granular
      bed using three-dimensional, time-resolved, particle tracking.
AB  - An experimental investigation into the interaction that occurs between an
      impacting water droplet and a granular bed of loose graded sand has been carried
      out. High-speed imaging, three-dimensional time-resolved particle tracking, and
      photogrammetric surface profiling have been used to examine individual impact
      events. The focus of the study is the quantification and trajectory analysis of
      the particles ejected from the sand bed, along with measurement of the change in
      bed morphology. The results from the experiments have detailed two distinct
      mechanisms of particle ejection: the ejection of water-encapsulated particles
      from the edge of the wetted region and the ejection of dry sand from the
      periphery of the impact crater. That the process occurs by these two distinct
      mechanisms has hitherto been unobserved. Presented in the paper are distributions
      of the particle ejection velocities, angles, and transport distances for both
      mechanisms. The ejected water-encapsulated particles, which are few in number,
      are characterized by low ejection angles and high ejection velocities, leading to
      large transport distances; the ejected dry particles, which are much greater in
      number, are characterized by high ejection angles and low velocities, leading to
      lower transport distances. From the particle ejection data, the momentum of the
      individual ballistic sand particles has been calculated; it was found that only
      2% of the water-droplet momentum at impact is transferred to the ballistic sand
      particles. In addition to the particle tracking, surface profiling of the
      granular bed postimpact has provided detailed information on its morphology;
      these data have demonstrated the consistent nature of the craters produced by the
      impact and suggest that particle agglomerations released from their edges make up
      about twice the number of particles involved in ballistic ejection. It is
      estimated that, overall, about 4% of the water-droplet momentum is taken up in
      particle movement. 

PMID- 24730832
TI  - Structural evolution in the packing of uniform spheres.
AB  - Structural analysis is very important to understanding the physics of atomic or
      particle systems of various types. However, properly characterizing the
      structures at different packing fraction rho is still a challenge. Here we
      analyze the local structure, in terms of the so-called common-neighbor-subcluster
      (CNS), of sphere packings with rho ? (0.2, 0.74). We show that although
      complicated in structure, there are totally 39 kinds of CNSs of which 12 are
      dominant. The evolution of these CNSs with the increase of rho is quantified, and
      the rules governing the evolution are explored. The results are found to be
      useful in constructing a comprehensive picture about the critical states and
      their transition in sphere packing. 

PMID- 24730833
TI  - Strain-rate-dependent model for the dynamic compression of elastoplastic spheres.
AB  - We present a force-displacement contact model for the compressive loading of
      elastoplastic spheres. This model builds from the well known Hertz contact law
      for elastic, quasistatic compression to incorporate a material's strain-rate
      dependent plasticity in order to describe collisions between particles. In the
      quasistatic regime, finite-element analysis is used to derive an empirical
      function of the material properties. A Johnson-Cook strain rate dependence is
      then included into the model to study dynamic effects. We validate the model
      using split Hopkinson bar experiments and show that the model can accurately
      simulate the force-displacement response of strain-rate-dependent elastoplastic
      spheres during dynamic compression and unloading. 

PMID- 24730834
TI  - Jamming by shape in kinetically constrained models.
AB  - We derive expressions for the critical density for jamming in a hyper-rhomboid
      system of arbitrary shape in any dimension for the Kob-Andersen and Fredrickson
      Andersen kinetically constrained models. We find that changing the system's shape
      without altering its total volume or particle density may induce jamming. We also
      find a transition between shapes in which the correlation length between jammed
      particles is infinite and shapes that have a finite correlation length. 

PMID- 24730835
TI  - Mesoscale and macroscale kinetic energy fluxes from granular fabric evolution.
AB  - Recent advances in high-resolution measurements means it is now possible to
      identify and track the local "fabric" or contact topology of individual grains in
      a deforming sand throughout loading history. These provide compelling impetus to
      the development of methods for inferring changes in the contact forces and
      energies at multiple spatiotemporal scales, using information on grain contacts
      alone. Here we develop a surrogate measure of the fluctuating kinetic energy
      based on changes in the local contact topology of individual grains. We
      demonstrate the method for dense granular materials under quasistatic biaxial
      shear. In these systems, the initially stable and solidlike response eventually
      gives way to liquidlike behavior and global failure. This crossover in mechanical
      behavior, akin to a phase transition, is marked by bursts of kinetic energy and
      frictional dissipation. Mechanisms underlying this release of energy include the
      buckling of major load-bearing structures known as force chains. These columns of
      grains represent major repositories for stored strain energy. Stored energy
      initially accumulates at all of the contacts along the force chain, but is
      released collectively when the chain overloads and buckles. The exact
      quantification of the buildup and release of energy in force chains, and the
      manner in which force chain buckling propagates in the sample (i.e., diffuse and
      systemwide versus localized into shear bands), requires detailed knowledge of
      contact forces. To date, however, the forces at grain contacts continue to elude
      measurement in natural granular materials like sand. Here, using data from
      computer simulations, we show that a proxy for the fluctuating kinetic energy in
      dense granular materials can be suitably constructed solely from the evolving
      properties of the grain's local contact topology. Our approach directly relates
      the evolution of fabric to energy flux and makes possible research into the
      propagation of failure from measurements of grain contacts in real granular
      materials. 

PMID- 24730836
TI  - Role of surface in apparent viscosity of glasses.
AB  - Two problems have intrigued experts for a long time: The one is within the
      context of the legend of flowing cathedral glass windows and the second is the
      inaccuracy appearing in very old thermometers of famous scientists. We relate
      this with the role of the surface on the apparent viscosity of glasses. The
      apparent viscosity could deviate from the bulk viscosity if the fraction w of the
      surface molecules, of small samples, is sufficiently large. The effect is more
      prominent at low temperatures, correspondingly at high viscosities. The
      interpretation is within the Avramov and Milchev viscosity model, combined with
      the predictions of the change of heat capacity for extremely small samples. We
      find that the apparent glass transition temperature could depend on the sample
      size, in agreement with experimental observations existing in the literature. In
      addition to glasses, the present results could be of importance for thin films
      and foams. 

PMID- 24730837
TI  - Nonlinear oscillations in an electrolyte solution under ac voltage.
AB  - The response of an electrolyte solution bounded between two blocking electrodes
      subjected to an ac voltage is considered. We focus on the pertinent thin-double
      layer limit, where this response is governed by a reduced dynamic model [L.
      Hojgaard Olesen, M. Z. Bazant, and H. Bruus, Phys. Rev. E 82, 011501 (2010)].
      During a transient stage, the system is nonlinearly entrained towards periodic
      oscillations of the same frequency as that of the applied voltage. Employing a
      strained-coordinate perturbation scheme, valid for moderately large values of the
      applied voltage amplitude V, we obtain a closed-form asymptotic approximation for
      the periodic orbit which is in remarkable agreement with numerical computations.
      The analysis elucidates the nonlinear characteristics of the system, including a
      slow (logarithmic) growth of the zeta-potential amplitude with V and a phase
      straining scaling as V-1lnV. In addition, an asymptotic current-voltage relation
      is provided, capturing the numerically observed rapid temporal variations in the
      electric current. 

PMID- 24730838
TI  - Correction of the power law of ac conductivity in ion-conducting materials due to
      the electrode polarization effect.
AB  - Based on the supposition related to fractal nature of transport processes in ion
      conducting materials, an expression for the low-frequency ac conductivity
      dependence was derived. This expression for the ac conductivity generalizes the
      power-law dependence and gives a possibility to take into account the influence
      of the electrode polarization effect. The ac conductivity expression obtained is
      in excellent agreement with experimental data for a wide frequency range. 

PMID- 24730839
TI  - Small-angle neutron scattering study of differences in phase behavior of silica
      nanoparticles in the presence of lysozyme and bovine serum albumin proteins.
AB  - The differences in phase behavior of anionic silica nanoparticles (88 A) in the
      presence of two globular proteins [cationic lysozyme (molecular weight (MW) 14.7
      kD) and anionic bovine serum albumin (BSA) (MW 66.4 kD)] have been studied by
      small-angle neutron scattering. The measurements were carried out on a fixed
      concentration (1 wt %) of Ludox silica nanoparticles with varying concentrations
      of proteins (0-5 wt %) at pH = 7. It is found that, despite having different
      natures (opposite charges), both proteins can render to the same kind of
      aggregation of silica nanoparticles. However, the concentration regions over
      which the aggregation is observed are widely different for the two proteins.
      Lysozyme with very small amounts (e.g., 0.01 wt %) leads to the aggregation of
      silica nanoparticles. On the other hand, silica nanoparticles coexist with BSA as
      independent entities at low protein concentrations and turn to aggregates at high
      protein concentrations (>1 wt %). In the case of lysozyme, the charge
      neutralization by the protein on the nanoparticles gives rise to the protein
      mediated aggregation of the nanoparticles. The nanoparticle aggregates coexist
      with unaggregated nanoparticles at low protein concentrations, whereas, they
      coexist with a free protein at higher protein concentrations. For BSA, the
      nonadsorbing nature of the protein produces the depletion force that causes the
      aggregation of the nanoparticles at higher protein concentrations. The evolution
      of the interaction is modeled by the two Yukawa potential, taking account of both
      attractive and repulsive terms of the interaction in these systems. The
      nanoparticle aggregation is found to be governed by the short-range attraction
      for lysozyme and the long-range attraction for BSA. The aggregates are
      characterized by the diffusion limited aggregate type of mass fractal morphology.

PMID- 24730840
TI  - Correlation potential of a test ion near a strongly charged plate.
AB  - We analytically calculate the correlation potential of a test ion near a strongly
      charged plate inside a dilute m:-n electrolyte. We do this by calculating the
      electrostatic Green's function in the presence of a nonlinear background
      potential, the latter having been obtained using the nonlinear Poisson-Boltzmann
      theory. We consider the general case where the dielectric constants of the plate
      and the electrolyte are distinct. The following generic results emerge from our
      analyses: (1) If the distance to the plate Deltaz is much larger than a Gouy
      Chapman length, the plate surface will behave effectively as an infinitely
      charged surface, and the dielectric constant of the plate effectively plays no
      role. (2) If Deltaz is larger than a Gouy-Chapman length but shorter than a Debye
      length, the correlation potential can be interpreted in terms of an image charge
      that is three times larger than the source charge. This behavior is independent
      of the valences of the ions. (3) The Green's function vanishes inside the plate
      if the surface charge density is infinitely large; hence the electrostatic
      potential is constant there. In this respect, a strongly charged plate behaves
      like a conductor plate. (4) If Deltaz is smaller than a Gouy-Chapman length, the
      correlation potential is dominated by the conventional image charge due to the
      dielectric discontinuity at the interface. (5) If Deltaz is larger than a Debye
      length, the leading order behavior of the correlation potential will depend on
      the valences of the ions in the electrolyte. Furthermore, inside an asymmetric
      electrolyte, the correlation potential is singly screened, i.e., it undergoes
      exponential decay with a decay width equal to the Debye length. 

PMID- 24730841
TI  - Single-file and normal diffusion of magnetic colloids in modulated channels.
AB  - Diffusive properties of interacting magnetic dipoles confined in a parabolic
      narrow channel and in the presence of a periodic modulated (corrugated) potential
      along the unconfined direction are studied using Brownian dynamics simulations.
      We compare our simulation results with the analytical result for the effective
      diffusion coefficient of a single particle by Festa and d'Agliano [Physica A 90,
      229 (1978)] and show the importance of interparticle interaction on the diffusion
      process. We present results for the diffusion of magnetic dipoles as a function
      of linear density, strength of the periodic modulation and commensurability
      factor. 

PMID- 24730842
TI  - Nonequilibrium noise in electrophoresis: the microion wind.
AB  - A colloid supported against gravitational settling by means of an imposed
      electric field behaves, on average, as if it is at equilibrium in a confining
      potential [T. M. Squires, J. Fluid Mech. 443, 403 (2001)]. We show, however, that
      the effective Langevin equation for the colloid contains a nonequilibrium noise
      source, proportional to the field, arising from the thermal motion of dissolved
      ions. The position fluctuations of the colloid show strong, experimentally
      testable signatures of nonequilibrium behavior, including a highly anisotropic,
      frequency-dependent "effective temperature" obtained from the fluctuation
      dissipation ratio. 

PMID- 24730843
TI  - Thermodiffusion in positively charged magnetic colloids: influence of the
      particle diameter.
AB  - The Soret coefficient (ST) of positively charged magnetic colloids was measured
      as a function of the nanoparticles' diameter. The Z-scan technique and the
      generalization of the thermal lens model proved to be a reliable technique to
      measure ST. We show that ST is negative and increases with the particle's
      diameter, being best described by a functional dependence of the type ST?d0.
      Potentiometric and conductometric experiments show that the particle's surface
      charge decreases as the temperature increases, changing the electrostatic
      interaction between the nanoparticles. The temperature gradient imposed in the
      ferrofluid by the Gaussian laser beam leads to the formation of the particle's
      concentration gradient. The origin of this phenomenon is discussed in terms of
      the decrease of the particle's surface charge in the hottest region of the sample
      and the thermoelectric field due to the inhomogeneous distribution of hydrogenous
      ions present in the colloidal suspension. 

PMID- 24730844
TI  - Magnetic particles confined in a modulated channel: structural transitions
      tunable by tilting a magnetic field.
AB  - The ground state of colloidal magnetic particles in a modulated channel are
      investigated as a function of the tilt angle of an applied magnetic field. The
      particles are confined by a parabolic potential in the transversal direction
      while in the axial direction a periodic substrate potential is present. By using
      Monte Carlo simulations, we construct a phase diagram for the different crystal
      structures as a function of the magnetic field orientation, strength of the
      modulated potential, and the commensurability factor of the system.
      Interestingly, we found first- and second-order phase transitions between
      different crystal structures, which can be manipulated by the orientation of the
      external magnetic field. A reentrant behavior is found between two- and four
      chain configurations, with continuous second-order transitions. Novel
      configurations are found consisting of frozen solitons of defects. By changing
      the orientation and/or strength of the magnetic field and/or the strength and
      periodicity of the substrate potential, the system transits through different
      phases. 

PMID- 24730845
TI  - Behavior of nanoparticle clouds around a magnetized microsphere under magnetic
      and flow fields.
AB  - When a micron-sized magnetizable particle is introduced into a suspension of
      nanosized magnetic particles, the nanoparticles accumulate around the
      microparticle and form thick anisotropic clouds extended in the direction of the
      applied magnetic field. This phenomenon promotes colloidal stabilization of
      bimodal magnetic suspensions and allows efficient magnetic separation of
      nanoparticles used in bioanalysis and water purification. In the present work,
      the size and shape of nanoparticle clouds under the simultaneous action of an
      external uniform magnetic field and the flow have been studied in detail. In
      experiments, a dilute suspension of iron oxide nanoclusters (of a mean diameter
      of 60 nm) was pushed through a thin slit channel with the nickel microspheres (of
      a mean diameter of 50 MUm) attached to the channel wall. The behavior of
      nanocluster clouds was observed in the steady state using an optical microscope.
      In the presence of strong enough flow, the size of the clouds monotonically
      decreases with increasing flow speed in both longitudinal and transverse magnetic
      fields. This is qualitatively explained by enhancement of hydrodynamic forces
      washing the nanoclusters away from the clouds. In the longitudinal field, the
      flow induces asymmetry of the front and the back clouds. To explain the flow and
      the field effects on the clouds, we have developed a simple model based on the
      balance of the stresses and particle fluxes on the cloud surface. This model,
      applied to the case of the magnetic field parallel to the flow, captures
      reasonably well the flow effect on the size and shape of the cloud and reveals
      that the only dimensionless parameter governing the cloud size is the ratio of
      hydrodynamic-to-magnetic forces-the Mason number. At strong magnetic interactions
      considered in the present work (dipolar coupling parameter alpha>=2), the
      Brownian motion seems not to affect the cloud behavior. 

PMID- 24730846
TI  - Effect of charge regulation on the stability of electrolyte films.
AB  - The stability of a thin liquid film of an electrolyte on a solid substrate is
      investigated. In the framework of the Debye-Huckel approximation, we show that
      the commonly used approximation of fixed potential at the solid-liquid interface
      does not lead to predictions of film rupture. To reconcile the model with
      experimental observations, we consider the constant charge density approximation
      for the solid substrate and then proceed to systematically investigate the
      effects of charge regulation based on a linear relationship between charge
      density and potential. Stability criteria are formulated in terms of charge
      regulation parameters and electrolyte properties, resulting in different types of
      stability diagrams. Critical thickness below which the film ruptures is shown to
      decrease as the charge regulation at the solid-liquid interface becomes stronger.

PMID- 24730847
TI  - Random walk on lattices: graph-theoretic approach to simulating long-range
      diffusion-attachment growth models.
AB  - Interest in thin-film fabrication for industrial applications have driven both
      theoretical and computational aspects of modeling its growth. One of the earliest
      attempts toward understanding the morphological structure of a film's surface is
      through a class of solid-on-solid limited-mobility growth models such as the
      Family, Wolf-Villain, or Das Sarma-Tamborenea models, which have produced
      fascinating surface roughening behaviors. These models, however, restrict the
      motion of an incidence atom to be within the neighborhood of its landing site,
      which renders them inept for simulating long-distance surface diffusion such as
      that observed in thin-film growth using a molecular-beam epitaxy technique. Naive
      extension of these models by repeatedly applying the local diffusion rules for
      each hop to simulate large diffusion length can be computationally very costly
      when certain statistical aspects are demanded. We present a graph-theoretic
      approach to simulating a long-range diffusion-attachment growth model. Using the
      Markovian assumption and given a local diffusion bias, we derive the transition
      probabilities for a random walker to traverse from one lattice site to the others
      after a large, possibly infinite, number of steps. Only computation with linear
      time complexity is required for the surface morphology calculation without other
      probabilistic measures. The formalism is applied, as illustrations, to simulate
      surface growth on a two-dimensional flat substrate and around a screw dislocation
      under the modified Wolf-Villain diffusion rule. A rectangular spiral ridge is
      observed in the latter case with a smooth front feature similar to that obtained
      from simulations using the well-known multiple registration technique. An
      algorithm for computing the inverse of a class of substochastic matrices is
      derived as a corollary. 

PMID- 24730848
TI  - Coexistence of spinodal instability and thermal nucleation in thin-film rupture:
      insights from molecular levels.
AB  - Despite extensive investigation using hydrodynamic models and experiments over
      the past decades, there remain open questions regarding the origin of the initial
      rupture of thin liquid films. One of the reasons that makes it difficult to
      identify the rupture origin is the coexistence of two dewetting mechanisms,
      namely, thermal nucleation and spinodal instability, as observed in many
      experimental studies. Using a coarse-grained model and large-scale molecular
      dynamics simulations, we are able to characterize the very early stage of
      dewetting in nanometer-thick liquid-metal films wetting a solid substrate. We
      observe the features characteristic of both spinodal instability and thermal
      nucleation in the spontaneously dewetting films and show that these two
      macroscopic mechanisms share a common origin at molecular levels. 

PMID- 24730849
TI  - Temperature distribution along the surface of evaporating droplets.
AB  - The surface temperature can significantly affect the flow field of drying
      droplets. Most previous studies assumed a monotonic temperature variation along
      the droplet surface. However, the present analyses indicate that a nonmonotonic
      spatial distribution of the surface temperature should occur. Three different
      patterns of the surface temperature distribution may appear during the
      evaporation process of liquid droplets: (i) the surface temperature increases
      monotonically from the center to the edge of the droplet; (ii) the surface
      temperature exhibits a nonmonotonic spatial distribution along the droplet
      surface; (iii) the surface temperature decreases monotonically from the center to
      the edge of the droplet. These surface temperature distributions can be explained
      by combining the evaporative cooling at the droplet surface and the heat
      conduction across the substrate and the liquid. Furthermore, a "phase diagram"
      for the distribution of the surface temperature is introduced and the effect of
      the spatial temperature distribution along the droplet surface on the flow
      structure of the droplet is discussed. The results may provide a better
      understanding of the Marangoni effect of drying droplets and provide a potential
      way to control evaporation-driven deposition as well as the assembly of colloids
      and other materials. 

PMID- 24730850
TI  - Scaling properties of planar discrete Poisson-Voronoi tessellations with von
      Neumann neighborhoods constructed according to the nucleation and growth
      mechanism.
AB  - In contrast to the conventional continual case, discrete Poisson-Voronoi
      tessellations resulting from the growth to impingement of random nuclei differ
      from tessellations constructed from the nearest tile loci. Previously studied
      tessellations were based directly on the notion of locus [A. Korobov, Phys. Rev.
      E 79, 031607 (2009); A. Korobov, Phys. Rev. E 87, 014401 (2013)]. This paper
      presents results for tessellations constructed by the growth of random nuclei.
      Their boundaries have a different structure and scaling properties are comparably
      more robust. One more scalable characteristic may be introduced for them, the
      perimeter distribution function, which is well approximated by the normal
      distribution function with the unit mean and the standard deviation equal to
      0.25. 

PMID- 24730851
TI  - Impact of nucleation on step-meandering instabilities during step-flow growth on
      vicinal surfaces.
AB  - Step-meandering instabilities can manifest during step-flow growth on vicinal
      surfaces [Bales and Zangwill, Phys. Rev. B 41, 5500 (1990); Pierre-Louis,
      D'Orsogna, and Einstein, Phys. Rev. Lett. 82, 3661 (1999)]. A phase diagram based
      on the various growth regimes of a vicinal surface allows us to study the impact
      of nucleation on these meanders and to predict a meandering instability caused by
      the nucleation and the coalescence of both islands and steps. Using an
      accelerated kinetic Monte Carlo method, we find that the coalescence of islands
      with steps produces large protrusions and deep ripples and that the resulting
      meandering instability is reinforced by the growth of the islands at almost the
      same positions from one monolayer to the other. A coarsening phenomenon occurs
      for the instability wavelength until mounds appear, favored by a large Ehrlich
      Schwoebel barrier. Such a meandering instability could be exploited for periodic
      self-assembly. 

PMID- 24730852
TI  - Peeling off an adhesive layer with spatially varying topography and shear
      modulus.
AB  - Inspired by recent experiments on hierarchically structured adhesives, we analyze
      here the effect of spatial variation in surface topography and shear modulus of
      an elastomeric adhesive on its ability to adhere strongly to a flexible
      contactor. The undulation of surface and modulus both were assumed to be periodic
      with periodicity, which is either identical or different for the two parameters;
      for identical periodicity, the phase lag between the respective undulations is
      also systematically varied. Calculations show that during continuous lifting of
      the flexible contactor from complete initial contact, the interfacial crack
      between the two adherents does not propagate continuously but intermittently,
      with crack arrest and initiation at the vicinity of minimum thickness and modulus
      of the layer; the torque required to initiate an arrested crack increases
      significantly over that required to propagate it on a smooth adhesive surface.
      The adhesion strength estimated from the corresponding force vs displacement plot
      is calculated to be higher than that achieved on a smooth and featureless
      adhesive surface. For in-phase variation in topography and shear modulus of the
      layer, the adhesive strength is found to be higher than for nonzero phase lag
      between the two parameters. The adhesion strength is found to diminish also for
      nonidentical periodicity between modulus and surface undulation. We have derived
      a scaling law for relating adhesion strength to several of these parameters. 

PMID- 24730854
TI  - Electrokinetic model for electric-field-induced interfacial instabilities.
AB  - Technology based on electric-field-induced instabilities on thin polymer film
      surfaces has emerged as a promising candidate for soft lithography. Typically,
      the instability is modeled using the perfect dielectric (PD) or the leaky
      dielectric (LD) model. These assume the electric diffuse layer to be
      infinitesimally large or small, respectively. In the present work we conduct
      stability analysis assuming a PD-electrolyte solution interface. The
      concentration of ions and, hence, the diffuse layer thickness is in general
      assumed to be of the same order as the electrolyte film thickness. The PD-LD
      models are then realized as limiting cases of the ratio of the double layer
      thickness to the film thickness. 

PMID- 24730853
TI  - Rough viscoelastic sliding contact: theory and experiments.
AB  - In this paper, we show how the numerical theory introduced by the authors
      [Carbone and Putignano, J. Mech. Phys. Solids 61, 1822 (2013)] can be effectively
      employed to study the contact between viscoelastic rough solids. The huge
      numerical complexity is successfully faced up by employing the adaptive
      nonuniform mesh developed by the authors in Putignano et al. [J. Mech. Phys.
      Solids 60, 973 (2012)]. Results mark the importance of accounting for
      viscoelastic effects to correctly simulate the sliding rough contact. In detail,
      attention is, first, paid to evaluate the viscoelastic dissipation, i.e., the
      viscoelastic friction. Fixed the sliding speed and the normal load, friction is
      completely determined. Furthermore, since the methodology employed in the work
      allows to study contact between real materials, a comparison between experimental
      outcomes and numerical prediction in terms of viscoelastic friction is shown. The
      good agreement seems to validate-at least partially-the presented methodology.
      Finally, it is shown that viscoelasticity entails not only the dissipative
      effects previously outlined, but is also strictly related to the anisotropy of
      the contact solution. Indeed, a marked anisotropy is present in the contact
      region, which results stretched in the direction perpendicular to the sliding
      speed. In the paper, the anisotropy of the deformed surface and of the contact
      area is investigated and quantified. 

PMID- 24730855
TI  - Redeposition of a straight-sided buckle under pressure.
AB  - The unilateral buckling of a stressed thin film on a substrate has been
      investigated theoretically in the framework of the Foppl-von Karman theory of
      thin plates when an increasing overpressure is considered onto the upper free
      surface of the film. It is found that, depending on the initial stress in the
      film and overpressure, two scenarios of evolution may occur. The snap-through of
      the one-dimensional buckle leading to the full redeposition should take place for
      low values of the initial stress. When the initial stress exceeds a critical
      value, a partial redeposition of the buckle should proceed as the overpressure
      increases. A snap-through while the redeposition mechanism has taken place should
      also occur for higher values of the overpressure. 

PMID- 24730856
TI  - Phase-field-crystal models and mechanical equilibrium.
AB  - Phase-field-crystal (PFC) models constitute a field theoretical approach to
      solidification, melting, and related phenomena at atomic length and diffusive
      time scales. One of the advantages of these models is that they naturally contain
      elastic excitations associated with strain in crystalline bodies. However,
      instabilities that are diffusively driven towards equilibrium are often orders of
      magnitude slower than the dynamics of the elastic excitations, and are thus not
      included in the standard PFC model dynamics. We derive a method to isolate the
      time evolution of the elastic excitations from the diffusive dynamics in the PFC
      approach and set up a two-stage process, in which elastic excitations are
      equilibrated separately. This ensures mechanical equilibrium at all times. We
      show concrete examples demonstrating the necessity of the separation of the
      elastic and diffusive time scales. In the small-deformation limit this approach
      is shown to agree with the theory of linear elasticity. 

PMID- 24730857
TI  - Wall-induced phase transition controlled by layering freezing.
AB  - Molecular dynamics simulations of the Lennard-Jones model are used to study phase
      transitions at a smooth surface. Our motivation is the observation that the
      existence of an attractive wall facilitates crystallization. To investigate how
      this wall influences phase transitions, the strength of wall-particle interaction
      is varied in our studies. We find that the phase behavior depends on the strength
      parameter alpha, i.e., the ratio between wall-particle and the particle-particle
      attraction strength. Three critical values of the ratio, namely, alphap, alphaw,
      and alphac, are used to define the qualitative nature of the phase behaviors at a
      smooth surface. Some interesting phenomena due to the increase of alpha are
      observed. First, a set of close-packed planes, i.e., {111} planes in fcc
      structures or {0001} planes in hcp structures, are "rotated" from intersecting to
      parallel to the wall when alpha = alphap; second, the layering phase transition
      close to the wall antecedes that of the bulk when alpha = alphaw. Finally, the
      first-order phase transition in the first two layers is supplanted by a
      continuous phase transition when alpha = alphac, which to some extent can be
      treated as a quasi-two-dimensional process. We find that bulk freezing always
      discontinuously occurs through a first-order phase transition, and seems to be
      isolated from the freezing process occurring close to the attractive surfaces.
      Moreover, during the heating process, we observe minimal dependence at a strongly
      attractive surface. 

PMID- 24730858
TI  - Complex superstructures in chiral liquid crystals: surface-induced helix
      destruction.
AB  - The influence of surface anchoring in thin chiral ferroelectric liquid crystals
      on helical superstructures imposed onto smectic layers is studied by means of a
      simple model allowing surface anchoring through the self-depolarization effect.
      It is shown that, for narrow temperature ranges close to temperatures of tilting
      phase transitions, these interactions can destroy helices, leading to the
      emergence of complex, intertwined undulatory, and helical substructures with
      different, mainly short, pitches. Regions with both undulated and helical
      orderings are demonstrated to reveal different sizes and random distributions
      along the smectic layer normal. Assuming values of material model parameters,
      typical for liquid crystals being close to tilting phase transitions, the free
      energy of thin helical smectic liquid crystal systems is determined as a function
      of two variables. One of them specifies the helix period of the appropriate bulk
      system (unperturbed by surfaces), while the second describes the interplay
      between the surface anchoring and the liquid crystal elasticity. It is shown that
      the free energy exhibits a very complicated behavior within variable regions for
      which the regular helices or complex superstructures occur. The resulting
      sensitivity of the free energy on changes of these variables corresponds to the
      appearance of a large variety of complex superstructures with coexisting helices
      of different periods. This gives an explanation of the occurrence of intricate
      superstructures and provides new insight into the interplay between molecular and
      surface interactions near the tilting phase transitions. 

PMID- 24730859
TI  - Cybotactic behavior in the de Vries smectic-A* liquid-crystal structure formed by
      a silicon-containing molecule.
AB  - We have identified a metastable liquid-crystal (LC) structure in the de Vries
      smectic-A* phase (de Vries Sm-A*) formed by silicon-containing molecules under
      certain boundary conditions. The phase transition with the metastable structure
      was observed in a LC droplet placed on a planar aligned substrate and LCs
      confined in the groove of a silicon microchannel. During the rapid cooling step,
      a batonnet structure was generated as an intermediate and metastable state prior
      to the transition that yielded the thermodynamically stable toric focal conic
      domains. This distinctive behavior was characterized using depolarized reflection
      light microscopy and grazing incidence x-ray diffraction techniques. We concluded
      that the silicon groups in the molecules that formed the de Vries phase induced
      the formation of layered clusters called cybotactic structures. This observation
      is relevant to an exploration of the physical properties of cybotactic de Vries
      phases and gives a hint as to their optoelectronic applications. 

PMID- 24730860
TI  - Chiral smectic transition phases appearing near the electric-field-induced phase
      transition observed by resonant microbeam x-ray scattering.
AB  - The electric-field-induced phase transition of a chiral liquid crystal containing
      Br revealed a transition phase between the three-layer periodicity ferrielectric
      phase and the synclinic ferroelectric phase in the electric field versus
      temperature phase diagram. Resonant x-ray scattering from the transition phase
      showed a diffuse streak or spotty weak reflections, which were composed of strong
      m/3-order (where m = 1 and 2) reflections and other weak peaks. The spotty
      reflections were found to be related to a 12-layer periodicity phase with a weak
      contribution from the 15-layer periodicity. An x-ray intensity analysis based on
      the Ising model suggested that the 12-layer periodicity phase was composed of two
      three-layer ferrielectric blocks and six synclinic layers. This model indicated
      that, in the transition phase, the three-layer ferrielectric molecular
      configuration gradually changed to the synclinic configuration. The diffuse
      streak appearing around m/3-order reflections near the field-induced transition
      from the four-layer periodicity phase to the synclinic ferroelectric phase is
      also discussed. 

PMID- 24730861
TI  - Measurements of the dielectric and viscoelastic constants in mixtures of 4,4'-n
      octyl-cyanobiphenyl and biphenyl.
AB  - We performed measurements of the dielectric constants, splay elastic constant,
      and rotational viscosity of the nematic phase of mixtures of 4,4'-n-octyl
      cyanobiphenyl (8CB) and biphenyl (BP). In contrast with previous results of
      DasGupta et al. [Phys. Rev. E 63, 041703 (2001); Phys. Lett. A 288, 323 (2001)],
      we do not find any anomaly of these constants when the smectic-A phase is
      approached at all concentrations of BP. These results are compatible with recent
      calorimetric measurements of Denolf et al. [Phys. Rev. Lett. 97, 107801 (2006);
      Phys. Rev. E 76, 051702 (2007)] and the absence of a tricritical point in the
      phase diagram. The origin of the anomalies observed by DasGupta et al. at large
      concentration of BP is also briefly discussed and a likely explanation in terms
      of biphenyl evaporation is proposed. 

PMID- 24730862
TI  - Elastic octopoles and colloidal structures in nematic liquid crystals.
AB  - We propose a simple theoretical model which explains the formation of dipolar two
      (2D) and three-dimensional (3D) colloidal structures in nematic liquid crystals.
      The colloidal particles are treated as effective hard spheres interacting via
      their elastic dipole, quadrupole, and octopole moments. It is shown that the
      octopole moment plays an important role in the formation of 2D and 3D nematic
      colloidal crystals. We generalize this assumption to the case of an external
      electric field and theoretically explain a giant electrostriction effect in 3D
      crystals observed recently. 

PMID- 24730863
TI  - Origin of weak layer contraction in de Vries smectic liquid crystals.
AB  - Structural investigations of the de Vries smectic-A (SmA) and smectic-C (SmC)
      phases of four mesogens containing a trisiloxane end segment reveal a linear
      molecular conformation in the SmA phase and a bent conformation resembling a
      hockey stick in the SmC phase. The siloxane and the hydrocarbon parts of the
      molecule tilt at different angles relative to the smectic layer normal and are
      oriented along different directions. For the compounds investigated, the shape of
      orientational distribution function (ODF) is found to be sugarloaf shaped and not
      the widely expected volcano like with positive orientational order parameters:
      ?P2? = 0.53-0.78, ?P4? = 0.14-0.45, and ?P6?~0.10. The increase in the effective
      molecular length, and consequently in the smectic layer spacing caused by reduced
      fluctuations and the corresponding narrowing of the ODF, counteracts the effect
      of molecular tilt and significantly reduces the SmC layer contraction. Maximum
      tilt of the hydrocarbon part of the molecule lies between approximately 18
      degrees  and 25 degrees  and between 6 degrees  and 12 degrees  for the siloxane
      part. The critical exponent of the tilt order parameter, beta~0.25, is in
      agreement with tricritical behavior at the SmA-SmC transition for two compounds
      and has lower value for first-order transition in the other compounds with finite
      enthalpy of transition. 

PMID- 24730864
TI  - Role of space charges on light-induced effects in nematic liquid crystals doped
      by methyl red.
AB  - We show that both the extraordinarily large nonlinear response and the light
      induced permanent reorientation in liquid crystals doped by the azo dye methyl
      red originates from the same phenomenon of modification of the charge density on
      the irradiated surface. The demonstration is done by applying ac voltage to the
      samples, showing that in this case no permanent anchoring is possible. The
      measurements confirm the role of photoisomerization that gives a transient
      contribution to the actual reorientation process only in the high dose regime.
      This result allows us to draw a picture for light-induced effects that might be
      applied to a large class of compounds. 

PMID- 24730865
TI  - Backflow-mediated domain switching in nematic liquid crystals.
AB  - We study the dynamics of the nematic liquid crystal kickback effect upon removal
      of a primary electric field and its amplification by a perpendicular secondary
      electric field resulting in the formation of domains with a reverse director
      orientation. Using computational fluid dynamics, we show that the domain
      formation is a robust phenomenon that takes place also in the complex case of
      multiple irregular random Freedericksz domains in three dimension as they appear
      in a realistic experimental situation. We propose domain switching by kickback
      amplification as a tool for self-insertion of shell-like inhomogeneities into an
      otherwise perfectly uniform director field configuration. 

PMID- 24730866
TI  - Generalizing the correlated chromophore domain model of reversible
      photodegradation to include the effects of an applied electric field.
AB  - All observations of photodegradation and self-healing follow the predictions of
      the correlated chromophore domain model [Ramini et al., Polym. Chem. 4, 4948
      (2013)]. In the present work, we generalize the domain model to describe the
      effects of an electric field by including induced dipole interactions between
      molecules in a domain by means of a self-consistent field approach. This electric
      field correction is added to the statistical mechanical model to calculate the
      distribution of domains that are central to healing. Also included in the model
      are the dynamics due to the formation of an irreversibly damaged species, which
      we propose involves damage to the polymer mediated through energy transfer from a
      dopant molecule after absorbing a photon. As in previous studies, the model with
      one-dimensional domains best explains all experimental data of the population as
      a function of time, temperature, intensity, concentration, and now applied
      electric field. Though the precise nature of a domain is yet to be determined,
      the fact that only one-dimensional domain models are consistent with observations
      suggests that they might be made of correlated dye molecules along polymer
      chains. Furthermore, the voltage-dependent measurements suggest that the largest
      polarizability axis of the molecules are oriented perpendicular to the chain. 

PMID- 24730867
TI  - Unfolding of collapsed polymers in shear flow: effects of colloid banding
      structures in confining channels.
AB  - Using hydrodynamic simulations, we demonstrate that confined colloidal
      suspensions can greatly enhance the unfolding of collapsed single polymers in
      flow. When colloids come in direct contact with the polymers due to the flow, the
      collapsed chains become flattened or elongated on the surface of the colloids,
      increasing the probability of forming large chain protrusions that the flow can
      pull out to unfold the polymers. This phenomenon may be suppressed if the colloid
      size is commensurate with the confining channels, where the colloids form well
      defined banding structures. Here, we analyze the colloid banding structures in
      detail and their relation to the chain unfolding. We find that for colloid volume
      fractions up to 30%, the confined colloids form simple cubic (sc), hexagonal
      (hex), or a mixture of sc + hex structures. By directly changing the heights of
      the confining channels, we show that the collapsed polymers unfold the most in
      the mixed sc + hex structures. The diffuse (not well-defined) bands in the mixed
      sc + hex structures provide the highest collision probability for the colloids
      and the polymers, thus enhancing unfolding the most. Without colloidal
      suspensions, we show that the confining channels alone do not have an observable
      effect on the unfolding of collapsed polymers. The well-defined colloid bands
      also suppress the unfolding of noncollapsed polymers. In fact, the average size
      for noncollapsed chains is even smaller in the well-defined bands than in a
      channel without any colloids. The appearance of well-defined bands in this case
      also indicates that lift forces experienced by the polymers in confinement are
      negligible compared to those exerted by the colloidal band structures. Our
      results may be important for understanding the dynamics of mixed colloid polymer
      solutions. 

PMID- 24730868
TI  - Physical theory of ionomer aggregation in water.
AB  - This article presents a physical theory for the aggregation of ionomer molecules
      in aqueous solution. To study this phenomenon, we consider a system of charged
      rigid rods with uniform surface charge immersed in water. The free-energy
      functional derived for this system consists of hydrophobic and direct
      electrostatic contributions as well as entropic terms. Energy minimization gives
      the stable aggregation number as a function of surface charge density, surface
      tension, geometric parameters, and density of rods in solution. We provide
      configuration diagrams of the system, which display the impact of the hydrophobic
      and electrostatic interaction strengths on the stabilization of finite-size
      bundles. 

PMID- 24730870
TI  - Using multitype branching processes to quantify statistics of disease outbreaks
      in zoonotic epidemics.
AB  - Branching processes have served as a model for chemical reactions, biological
      growth processes, and contagion (of disease, information, or fads). Through this
      connection, these seemingly different physical processes share some common
      universalities that can be elucidated by analyzing the underlying branching
      process. In this work we focus on coupled branching processes as a model of
      infectious diseases spreading from one population to another. An exceedingly
      important example of such coupled outbreaks are zoonotic infections that spill
      over from animal populations to humans. We derive several statistical quantities
      characterizing the first spillover event from animals to humans, including the
      probability of spillover, the first passage time distribution for human
      infection, and disease prevalence in the animal population at spillover. Large
      stochastic fluctuations in those quantities can make inference of the state of
      the system at the time of spillover difficult. Focusing on outbreaks in the human
      population, we then characterize the critical threshold for a large outbreak, the
      distribution of outbreak sizes, and associated scaling laws. These all show a
      strong dependence on the basic reproduction number in the animal population and
      indicate the existence of a novel multicritical point with altered scaling
      behavior. The coupling of animal and human infection dynamics has crucial
      implications, most importantly allowing for the possibility of large human
      outbreaks even when human-to-human transmission is subcritical. 

PMID- 24730869
TI  - Mathematical model of alternative mechanism of telomere length maintenance.
AB  - Biopolymer length regulation is a complex process that involves a large number of
      biological, chemical, and physical subprocesses acting simultaneously across
      multiple spatial and temporal scales. An illustrative example important for
      genomic stability is the length regulation of telomeres-nucleoprotein structures
      at the ends of linear chromosomes consisting of tandemly repeated DNA sequences
      and a specialized set of proteins. Maintenance of telomeres is often facilitated
      by the enzyme telomerase but, particularly in telomerase-free systems, the
      maintenance of chromosomal termini depends on alternative lengthening of
      telomeres (ALT) mechanisms mediated by recombination. Various linear and circular
      DNA structures were identified to participate in ALT, however, dynamics of the
      whole process is still poorly understood. We propose a chemical kinetics model of
      ALT with kinetic rates systematically derived from the biophysics of DNA
      diffusion and looping. The reaction system is reduced to a coagulation
      fragmentation system by quasi-steady-state approximation. The detailed treatment
      of kinetic rates yields explicit formulas for expected size distributions of
      telomeres that demonstrate the key role played by the J factor, a quantitative
      measure of bending of polymers. The results are in agreement with experimental
      data and point out interesting phenomena: an appearance of very long telomeric
      circles if the total telomere density exceeds a critical value (excess mass) and
      a nonlinear response of the telomere size distributions to the amount of
      telomeric DNA in the system. The results can be of general importance for
      understanding dynamics of telomeres in telomerase-independent systems as this
      mode of telomere maintenance is similar to the situation in tumor cells lacking
      telomerase activity. Furthermore, due to its universality, the model may also
      serve as a prototype of an interaction between linear and circular DNA structures
      in various settings. 

PMID- 24730871
TI  - Inferring the spatiotemporal DNA replication program from noisy data.
AB  - We generalize a stochastic model of DNA replication to the case where replication
      origin-initiation rates vary locally along the genome and with time. Using this
      generalized model, we address the inverse problem of inferring initiation rates
      from experimental data concerning replication in cell populations. Previous work
      based on curve fitting depended on arbitrarily chosen functional forms for the
      initiation rate, with free parameters that were constrained by the data. We
      introduce a nonparametric method of inference that is based on Gaussian process
      regression. The method replaces specific assumptions about the functional form of
      the initiation rate with more general prior expectations about the smoothness of
      variation of this rate, along the genome and in time. Using this inference
      method, we recover, with high precision, simulated replication schemes from noisy
      data that are typical of current experiments. 

PMID- 24730872
TI  - Nonequilibrium structure and dynamics in a microscopic model of thin-film active
      gels.
AB  - In the presence of adenosine triphosphate, molecular motors generate active force
      dipoles that drive suspensions of protein filaments far from thermodynamic
      equilibrium, leading to exotic dynamics and pattern formation. Microscopic
      modeling can help to quantify the relationship between individual motors plus
      filaments to organization and dynamics on molecular and supramolecular length
      scales. Here, we present results of extensive numerical simulations of active
      gels where the motors and filaments are confined between two infinite parallel
      plates. Thermal fluctuations and excluded-volume interactions between filaments
      are included. A systematic variation of rates for motor motion, attachment, and
      detachment, including a differential detachment rate from filament ends, reveals
      a range of nonequilibrium behavior. Strong motor binding produces structured
      filament aggregates that we refer to as asters, bundles, or layers, whose
      stability depends on motor speed and differential end detachment. The gross
      features of the dependence of the observed structures on the motor rate and the
      filament concentration can be captured by a simple one-filament model. Loosely
      bound aggregates exhibit superdiffusive mass transport, where filament
      translocation scales with lag time with nonunique exponents that depend on motor
      kinetics. An empirical data collapse of filament speed as a function of motor
      speed and end detachment is found, suggesting a dimensional reduction of the
      relevant parameter space. We conclude by discussing the perspectives of
      microscopic modeling in the field of active gels. 

PMID- 24730873
TI  - Motor control of sound frequency in birdsong involves the interaction between air
      sac pressure and labial tension.
AB  - Frequency modulation is a salient acoustic feature of birdsong. Its control is
      usually attributed to the activity of syringeal muscles, which affect the tension
      of the labia responsible for sound production. We use experimental and
      theoretical tools to test the hypothesis that for birds producing tonal sounds
      such as domestic canaries (Serinus canaria), frequency modulation is determined
      by both the syringeal tension and the air sac pressure. For different models, we
      describe the structure of the isofrequency curves, which are sets of parameters
      leading to sounds presenting the same fundamental frequencies. We show how their
      shapes determine the relative roles of syringeal tension and air sac pressure in
      frequency modulation. Finally, we report experiments that allow us to unveil the
      features of the isofrequency curves. 

PMID- 24730874
TI  - RNA topology remolds electrostatic stabilization of viruses.
AB  - Simple RNA viruses efficiently encapsulate their genome into a nano-sized protein
      shell: the capsid. Spontaneous coassembly of the genome and the capsid proteins
      is driven predominantly by electrostatic interactions between the negatively
      charged RNA and the positively charged inner capsid wall. Using field theoretic
      formulation we show that the inherently branched RNA secondary structure allows
      viruses to maximize the amount of encapsulated genome and make assembly more
      efficient, allowing viral RNAs to out-compete cellular RNAs during replication in
      infected host cells. 

PMID- 24730875
TI  - DNA damage may drive nucleosomal reorganization to facilitate damage detection.
AB  - One issue in genome maintenance is how DNA repair proteins find lesions at rates
      that seem to exceed diffusion-limited search rates. We propose a phenomenon where
      DNA damage induces nucleosomal rearrangements which move lesions to potential
      rendezvous points in the chromatin structure. These rendezvous points are the
      dyad and the linker DNA between histones, positions in the chromatin which are
      more likely to be accessible by repair proteins engaged in a random search. The
      feasibility of this mechanism is tested by considering the statistical mechanics
      of DNA containing a single lesion wrapped onto the nucleosome. We consider
      lesions which make the DNA either more flexible or more rigid by modeling the
      lesion as either a decrease or an increase in the bending energy. We include this
      energy in a partition function model of nucleosome breathing. Our results
      indicate that the steady state for a breathing nucleosome will most likely
      position the lesion at the dyad or in the linker, depending on the energy of the
      lesion. A role for DNA binding proteins and chromatin remodelers is suggested
      based on their ability to alter the mechanical properties of the DNA and DNA
      histone binding, respectively. We speculate that these positions around the
      nucleosome potentially serve as rendezvous points where DNA lesions may be
      encountered by repair proteins which may be sterically hindered from searching
      the rest of the nucleosomal DNA. The strength of the repositioning is strongly
      dependent on the structural details of the DNA lesion and the wrapping and
      breathing of the nucleosome. A more sophisticated evaluation of this proposed
      mechanism will require detailed information about breathing dynamics, the
      structure of partially wrapped nucleosomes, and the structural properties of
      damaged DNA. 

PMID- 24730876
TI  - Inherent randomness of evolving populations.
AB  - The entropy rates of the Wright-Fisher process, the Moran process, and
      generalizations are computed and used to compare these processes and their
      dependence on standard evolutionary parameters. Entropy rates are measures of the
      variation dependent on both short-run and long-run behaviors and allow the
      relationships between mutation, selection, and population size to be examined.
      Bounds for the entropy rate are given for the Moran process (independent of
      population size) and for the Wright-Fisher process (bounded for fixed population
      size). A generational Moran process is also presented for comparison to the
      Wright-Fisher Process. Results include analytic results and computational
      extensions. 

PMID- 24730877
TI  - Vanishing amplitude of backbone dynamics causes a true protein dynamical
      transition: 2H NMR studies on perdeuterated C-phycocyanin.
AB  - Using a combination of H2 nuclear magnetic resonance (NMR) methods, we study
      internal rotational dynamics of the perdeuterated protein C-phycocyanin (CPC) in
      dry and hydrated states over broad temperature and dynamic ranges with high
      angular resolution. Separating H2 NMR signals from methyl deuterons, we show that
      basically all backbone deuterons exhibit highly restricted motion occurring on
      time scales faster than microseconds. The amplitude of this motion increases when
      a hydration shell exists, while it decreases upon cooling and vanishes near 175
      K. We conclude that the vanishing of the highly restricted motion marks a
      dynamical transition, which is independent of the time window and of a
      fundamental importance. This conclusion is supported by results from experimental
      and computational studies of the proteins myoglobin and elastin. In particular,
      we argue based on findings in molecular dynamics simulations that the behavior of
      the highly restricted motion of proteins at the dynamical transition resembles
      that of a characteristic secondary relaxation of liquids at the glass transition,
      namely the nearly constant loss. Furthermore, H2 NMR studies on perdeuterated CPC
      reveal that, in addition to highly restricted motion, small fractions of backbone
      segments exhibit weakly restricted dynamics when temperature and hydration are
      sufficiently high. 

PMID- 24730878
TI  - Length-dependent beta-sheet growth mechanisms of polyalanine peptides in water
      and on hydrophobic surfaces.
AB  - Fibrillar assemblies by peptides are becoming one of the most promising
      nanomaterials due to their exceptional properties. The self-assembly of peptides
      into beta sheets is a critical step in the fibrillization pathway. We
      investigated the length-dependent beta-sheet growth mechanisms of polyalanine
      [poly(A)] peptides consisting of 6 to 24 alanines (A6 to A24) in water and on the
      hydrophobic surface, respectively, by molecular dynamics simulations. beta-sheet
      growth behavior in water fits negative exponential growth model, showing that
      beta-sheet growth rate decays exponentially with time. Meanwhile, increasing
      chain length leads to an accelerated decay of the beta-sheet growth rate. By
      contrast, beta-sheet growth on the surface from A6 to A18 occurs in two
      consecutive stages, both of which fit linear growth models. beta-sheet growth
      rate in the first stage increases as chain length is increased, while the
      intermediate length peptide A12 has the highest beta-sheet growth rate in the
      second stage. beta-sheet growth behavior of A24 on the surface still fits
      negative exponential model. Overall, the hydrophobic surface accelerates beta
      sheet growth by enhancing local concentration and reducing conformational entropy
      of poly(A) peptide, and the beta-sheet growth of the intermediate length peptide
      A12 is the fastest on the surface. Our simulation results shed light on
      understanding the accelerated peptide fibrillization on the hydrophobic surface. 

PMID- 24730879
TI  - Nucleation-conversion-polymerization reactions of biological macromolecules with
      prenucleation clusters.
AB  - The self-assembly of biomolecules, such as peptides and proteins, into filaments
      is conventionally understood as a nucleated polymerization reaction. However,
      detailed analysis of experimental observation has revealed recently that
      nucleation pathways generate growth-competent nuclei via a cascade of metastable
      intermediate species, which are omitted in conventional models of filamentous
      growth based on classical nucleation theory. Here we take an analytical approach
      to generalizing the classical theory of nucleated polymerization to include the
      formation of these prenucleation clusters, providing a quantitative general
      classification of the behavior exhibited by these nucleation-conversion
      polymerization reactions. A phase diagram is constructed, and analytical
      predictions are derived for key experimental observables. Using this approach, we
      delineate the characteristic time scales that determine the nature of biopolymer
      growth phenomena. 

PMID- 24730880
TI  - Role of functionality in two-component signal transduction: a stochastic study.
AB  - We present a stochastic formalism for signal transduction processes in a
      bacterial two-component system. Using elementary mass action kinetics, the
      proposed model takes care of signal transduction in terms of a phosphotransfer
      mechanism between the cognate partners of a two-component system, viz., the
      sensor kinase and the response regulator. Based on the difference in
      functionality of the sensor kinase, the noisy phosphotransfer mechanism has been
      studied for monofunctional and bifunctional two-component systems using the
      formalism of the linear noise approximation. Steady-state analysis of both models
      quantifies different physically realizable quantities, e.g., the variance, the
      Fano factor (variance/mean), and mutual information. The resultant data reveal
      that both systems reliably transfer information of extracellular environment
      under low external stimulus and in a high-kinase-and-phosphatase regime. We
      extend our analysis further by studying the role of the two-component system in
      downstream gene regulation. 

PMID- 24730881
TI  - Interacting motile agents: taking a mean-field approach beyond monomers and
      nearest-neighbor steps.
AB  - We consider a discrete agent-based model on a one-dimensional lattice, where each
      agent occupies L sites and attempts movements over a distance of d lattice sites.
      Agents obey a strict simple exclusion rule. A discrete-time master equation is
      derived using a mean-field approximation and careful probability arguments. In
      the continuum limit, nonlinear diffusion equations that describe the average
      agent occupancy are obtained. Averaged discrete simulation data are generated and
      shown to compare very well with the solution to the derived nonlinear diffusion
      equations. This framework allows us to approach a lattice-free result using all
      the advantages of lattice methods. Since different cell types have different
      shapes and speeds of movement, this work offers insight into population-level
      behavior of collective cellular motion. 

PMID- 24730882
TI  - Fluctuations of cell population in a colonic crypt.
AB  - The number of stem cells in a colonic crypt is often very small, which leads to
      large intrinsic fluctuations in the cell population. Based on the model of cell
      population dynamics with linear feedback in a colonic crypt, we present a
      stochastic dynamics of the cell population [including stem cells (SCs), transit
      amplifying cells (TACs), and fully differentiated cells (FDCs)]. The Fano factor,
      covariance, and susceptibility formulas of the cell population around the steady
      state are derived by using the Langevin theory. In the range of physiologically
      reasonable parameter values, it is found that the stationary populations of TACs
      and FDCs exhibit an approximately threshold behavior as a function of the net
      growth rate of TACs, and the reproductions of TACs and FDCs can be classified
      into three regimens: controlled, crossover, and uncontrolled. With the increasing
      of the net growth rate of TACs, there is a maximum of the relative intrinsic
      fluctuations (i.e., the Fano factors) of TACs and FDCs in the crossover region.
      For a fixed differentiation rate and the net growth rate of SCs, the covariance
      of fluctuations between SCs and TACs has a maximum in the crossover region.
      However, the susceptibilities of both TACs and FDCs to the net growth rate of
      TACs have a minimum in the crossover region. 

PMID- 24730883
TI  - Stochastic resonance in an intracellular genetic perceptron.
AB  - Intracellular genetic networks are more intelligent than was first assumed due to
      their ability to learn. One of the manifestations of this intelligence is the
      ability to learn associations of two stimuli within gene-regulating circuitry:
      Hebbian-type learning within the cellular life. However, gene expression is an
      intrinsically noisy process; hence, we investigate the effect of intrinsic and
      extrinsic noise on this kind of intracellular intelligence. We report a
      stochastic resonance in an intracellular associative genetic perceptron, a noise
      induced phenomenon, which manifests itself in noise-induced increase of response
      in efficiency after the learning event under the conditions of optimal
      stochasticity. 

PMID- 24730884
TI  - Hydrodynamic interaction between overlapping domains during recurrence of
      registration within planar lipid bilayer membranes.
AB  - Due to a thermodynamic coupling between the two leaflets comprising a lipid
      bilayer, compositional lipid domains residing within opposing leaflets are often
      found in registry. If the system is perturbed by displacing one domain relative
      to the other, diffusive and advective lipid fluxes are established to restore
      equilibrium and reestablish domain overlap. In this work, we focus on the
      advective part of the process, and first derive an analytical expression for the
      hydrodynamic drag coefficient associated with the advective flow for the special
      case of perfect domain overlap. The resulting expression identifies parameter
      regions where sliding friction between the leaflets dominates over viscous
      dissipation within the leaflets or vice versa. It is shown that in all
      practically relevant cases, sliding friction between the leaflets is the dominant
      factor. Finally, we investigate the domain separation dependence of the
      hydrodynamic drag coefficient via direct simulations of a continuum diffuse
      interface model, and provide useful empirical expressions for its behavior. 

PMID- 24730885
TI  - Optimal search in interacting populations: Gaussian jumps versus Levy flights.
AB  - We investigated the relationships between search efficiency, movement strategy,
      and nonlocal communication in the biological context of animal foraging. We
      considered situations where the members of a population of foragers perform
      either Gaussian jumps or Levy flights, and show that the search time is minimized
      when communication among individuals occurs at intermediate ranges, independently
      of the type of movement. Additionally, while Brownian strategies are more
      strongly influenced by the communication mechanism, Levy flights still result in
      shorter overall search durations. 

PMID- 24730886
TI  - Localization phenomena in a DNA double-helix structure: a twisted ladder model.
AB  - In this work we propose a model for the DNA double helix within the tight-binding
      framework that incorporates the helicity of the molecules. We have studied the
      localization properties of three DNA sequences, the periodic poly(dG)-poly(dC)
      and poly(dA)-poly(dT) sequences and the random ATGC sequence (where A is adenine,
      T is thymine, G is guanine, and C is cytosine), all of which are coupled to the
      backbone with random site energies representing the environmental fluctuations.
      We observe that due to the helicity of DNA, electron transport is greatly
      enhanced and there exists an almost disorder-strength-independent critical value
      of the hopping integral, which accounts for the helicity of DNA, for which the
      electronic states become maximally extended. We have also investigated the effect
      of backbone energetics on the transmission and I-V characteristics of DNA. 

PMID- 24730887
TI  - Geometrical guidance and trapping transition of human sperm cells.
AB  - The guidance of human sperm cells under confinement in quasi-2D microchambers is
      investigated using a purely physical method to control their distribution.
      Transport property measurements and simulations are performed with diluted sperm
      populations, for which effects of geometrical guidance and concentration are
      studied in detail. In particular, a trapping transition at convex angular wall
      features is identified and analyzed. We also show that highly efficient
      microratchets can be fabricated by using curved asymmetric obstacles to take
      advantage of the spermatozoa specific swimming strategy. 

PMID- 24730888
TI  - Human turnover dynamics during sleep: statistical behavior and its modeling.
AB  - Turnover is a typical intermittent body movement while asleep. Exploring its
      behavior may provide insights into the mechanisms and management of sleep.
      However, little is understood about the dynamic nature of turnover in healthy
      humans and how it can be modified in disease. Here we present a detailed analysis
      of turnover signals that are collected by accelerometry from healthy elderly
      subjects and age-matched patients with neurodegenerative disorders such as
      Parkinson's disease. In healthy subjects, the time intervals between consecutive
      turnover events exhibit a well-separated bimodal distribution with one mode at
      ?10 s and the other at ?100 s, whereas such bimodality tends to disappear in
      neurodegenerative patients. The discovery of bimodality and fine temporal
      structures (?10 s) is a contribution that is not revealed by conventional sleep
      recordings with less time resolution (~30 s). Moreover, we estimate the scaling
      exponent of the interval fluctuations, which also shows a clear difference
      between healthy subjects and patients. We incorporate these experimental results
      into a computational model of human decision making. A decision is to be made at
      each simulation step between two choices: to keep on sleeping or to make a
      turnover, the selection of which is determined dynamically by comparing a pair of
      random numbers assigned to each choice. This decision is weighted by a single
      parameter that reflects the depth of sleep. The resulting simulated behavior
      accurately replicates many aspects of observed turnover patterns, including the
      appearance or disappearance of bimodality and leads to several predictions,
      suggesting that the depth parameter may be useful as a quantitative measure for
      differentiating between normal and pathological sleep. These findings have
      significant clinical implications and may pave the way for the development of
      practical sleep assessment technologies. 

PMID- 24730889
TI  - Cooperative action of KIF1A Brownian motors with finite dwell time.
AB  - We study in detail the cooperative action of small groups of KIF1A motors in its
      monomeric (single-headed) form within an arrangement relevant to vesicle traffic
      or membrane tube extraction. It has been recently shown that under these
      circumstances, the presence of a finite dwell time in the motor cycle contributes
      to remarkably enhance collective force generation [D. Oriola and J. Casademunt,
      Phys. Rev. Lett. 111, 048103 (2013)]. We analyze this mechanism in detail by
      means of a two-state noise-driven ratchet model with hard-core repulsive
      interactions. We obtain staircase-shaped velocity-force curves and show that
      motors self-organize in clusters with a nontrivial force distribution that
      conveys a large part of the load to the central motors. Under heavy loads, large
      clusters adopt a synchronic mode of totally asymmetric steps. We also find a
      dramatic increase of the collective efficiency with the number of motors.
      Finally, we complete the study by addressing different interactions that impose
      spatial constraints such as rigid coupling and raft-induced confinement. Our
      results reinforce the hypothesis that the specificity of KIF1A to axonal
      vesicular transport may be deeply related to its high cooperativity. 

PMID- 24730890
TI  - Impact of morphology on diffusive dynamics on curved surfaces.
AB  - Diffusive processes on nonplanar substrates are deeply relevant for cellular
      function and transport and increasingly used to probe and characterize the
      behavior of proteins in membranes. We present analytical and numerical analyses
      of in-plane diffusion of discrete particles on curved geometries reflecting
      various generic motifs in biology and explore, in particular, the effect that the
      shape of the substrate has on the characteristic time scales of diffusive
      processes. To this end, we consider both collective measures (the relaxation of
      concentration profiles towards equilibrium) and single-particle measures (escape
      rates and first passage times of individual diffusing molecules): the first
      relevant for the correct interpretation of FRAP experiments in curved
      environments; the second, for single-particle tracking probes. Each of these
      measures is sensitively affected by the morphology of the substrate, and we find
      that the exit rate out of a domain is not uniquely set by the size of its
      boundary, illustrating the general principle we reveal: By varying the shape of a
      substrate, Nature can control the diffusive time scales in a microenvironment
      without changing the bare substrate properties. 

PMID- 24730891
TI  - Self-localized states in species competition.
AB  - We study the conditions under which species interaction, as described by
      continuous versions of the competitive Lotka-Volterra model (namely the nonlocal
      Kolmogorov-Fisher model, and its differential approximation), can support the
      existence of localized states, i.e., patches of species with enhanced population
      surrounded in niche space by species at smaller densities. These states would
      arise from species interaction, and not by any preferred niche location or better
      fitness. In contrast to previous works we include only quadratic nonlinearities,
      so that the localized patches appear on a background of homogeneously distributed
      species coexistence, instead of on top of the no-species empty state. For the
      differential model we find and describe in detail the stable localized states.
      For the full nonlocal model, however, competitive interactions alone do not allow
      the conditions for the observation of self-localized states, and we show how the
      inclusion of additional facilitative interactions leads to the appearance of
      them. 

PMID- 24730892
TI  - Optimal size of stochastic Hodgkin-Huxley neuronal systems for maximal energy
      efficiency in coding pulse signals.
AB  - The generation and conduction of action potentials (APs) represents a fundamental
      means of communication in the nervous system and is a metabolically expensive
      process. In this paper, we investigate the energy efficiency of neural systems in
      transferring pulse signals with APs. By analytically solving a bistable neuron
      model that mimics the AP generation with a particle crossing the barrier of a
      double well, we find the optimal number of ion channels that maximizes the energy
      efficiency of a neuron. We also investigate the energy efficiency of a neuron
      population in which the input pulse signals are represented with synchronized
      spikes and read out with a downstream coincidence detector neuron. We find an
      optimal number of neurons in neuron population, as well as the number of ion
      channels in each neuron that maximizes the energy efficiency. The energy
      efficiency also depends on the characters of the input signals, e.g., the pulse
      strength and the interpulse intervals. These results are confirmed by computer
      simulation of the stochastic Hodgkin-Huxley model with a detailed description of
      the ion channel random gating. We argue that the tradeoff between signal
      transmission reliability and energy cost may influence the size of the neural
      systems when energy use is constrained. 

PMID- 24730893
TI  - Statistical validation of high-dimensional models of growing networks.
AB  - The abundance of models of complex networks and the current insufficient
      validation standards make it difficult to judge which models are strongly
      supported by data and which are not. We focus here on likelihood maximization
      methods for models of growing networks with many parameters and compare their
      performance on artificial and real datasets. While high dimensionality of the
      parameter space harms the performance of direct likelihood maximization on
      artificial data, this can be improved by introducing a suitable penalization
      term. Likelihood maximization on real data shows that the presented approach is
      able to discriminate among available network models. To make large-scale datasets
      accessible to this kind of analysis, we propose a subset sampling technique and
      show that it yields substantial model evidence in a fraction of time necessary
      for the analysis of the complete data. 

PMID- 24730894
TI  - Local paths to global coherence: cutting networks down to size.
AB  - How does connectivity impact network dynamics? We address this question by
      linking network characteristics on two scales. On the global scale, we consider
      the coherence of overall network dynamics. We show that such global coherence in
      activity can often be predicted from the local structure of the network. To
      characterize local network structure, we use "motif cumulants," a measure of the
      deviation of pathway counts from those expected in a minimal probabilistic
      network model. We extend previous results in three ways. First, we give
      acombinatorial formulation of motif cumulants that relates to the allied concept
      in probability theory. Second, we show that the link between global network
      dynamics and local network architecture is strongly affected by heterogeneity in
      network connectivity. However, we introduce a network-partitioning method that
      recovers a tight relationship between architecture and dynamics. Third, for a
      particular set of models, we generalize the underlying theory to treat dynamical
      coherence at arbitrary orders (i.e., triplet correlations and beyond). We show
      that at any order, only a highly restricted set of motifs impacts dynamical
      correlations. 

PMID- 24730895
TI  - Crosstalk and transitions between multiple spatial maps in an attractor neural
      network model of the hippocampus: collective motion of the activity.
AB  - The dynamics of a neural model for hippocampal place cells storing spatial maps
      is studied. In the absence of external input, depending on the number of cells
      and on the values of control parameters (number of environments stored, level of
      neural noise, average level of activity, connectivity of place cells), a "clump"
      of spatially localized activity can diffuse or remains pinned due to crosstalk
      between the environments. In the single-environment case, the macroscopic
      coefficient of diffusion of the clump and its effective mobility are calculated
      analytically from first principles and corroborated by numerical simulations. In
      the multienvironment case the heights and the widths of the pinning barriers are
      analytically characterized with the replica method; diffusion within one map is
      then in competition with transitions between different maps. Possible mechanisms
      enhancing mobility are proposed and tested. 

PMID- 24730896
TI  - Structural measures for multiplex networks.
AB  - Many real-world complex systems consist of a set of elementary units connected by
      relationships of different kinds. All such systems are better described in terms
      of multiplex networks, where the links at each layer represent a different type
      of interaction between the same set of nodes rather than in terms of (single
      layer) networks. In this paper we present a general framework to describe and
      study multiplex networks, whose links are either unweighted or weighted. In
      particular, we propose a series of measures to characterize the multiplexicity of
      the systems in terms of (i) basic node and link properties such as the node
      degree, and the edge overlap and reinforcement, (ii) local properties such as the
      clustering coefficient and the transitivity, and (iii) global properties related
      to the navigability of the multiplex across the different layers. The measures we
      introduce are validated on a genuinely multiplex data set of Indonesian
      terrorists, where information among 78 individuals are recorded with respect to
      mutual trust, common operations, exchanged communications, and business
      relationships. 

PMID- 24730897
TI  - Capital death in the world market.
AB  - We study the gross domestic product (GDP) per capita together with the market
      capitalization (MCAP) per capita as two indicators of the effect of
      globalization. We find that g, the GDP per capita, as a function of m, the MCAP
      per capita, follows a power law with average exponent close to 1/3. In addition,
      the Zipf ranking approach confirms that the m for countries with initially lower
      values of m tends to grow more rapidly than for countries with initially larger
      values of m. If the trends over the past 20 years continue to hold in the future,
      then the Zipf ranking approach leads to the prediction that in about 50 years,
      all countries participating in globalization will have comparable values of their
      MCAP per capita. We call this economic state "capital death," in analogy to the
      physics state of "heat death" predicted by thermodynamic arguments. 

PMID- 24730898
TI  - Game theory in models of pedestrian room evacuation.
AB  - We analyze the pedestrian evacuation of a rectangular room with a single door
      considering a lattice gas scheme with the addition of behavioral aspects of the
      pedestrians. The movement of the individuals is based on random and rational
      choices and is affected by conflicts between two or more agents that want to
      advance to the same position. Such conflicts are solved according to certain
      rules closely related to the concept of strategies in game theory, cooperation
      and defection. We consider game rules analogous to those from the Prisoner's
      Dilemma and Stag Hunt games, with payoffs associated to the probabilities of the
      individuals to advance to the selected site. We find that, even when defecting is
      the rational choice for any agent, under certain conditions, cooperators can take
      advantage from mutual cooperation and leave the room more rapidly than defectors.

PMID- 24730899
TI  - Temporal percolation in activity-driven networks.
AB  - We study the temporal percolation properties of temporal networks by taking as a
      representative example the recently proposed activity-driven-network model [N.
      Perra et al., Sci. Rep. 2, 469 (2012)]. Building upon an analytical framework
      based on a mapping to hidden variables networks, we provide expressions for the
      percolation time Tp marking the onset of a giant connected component in the
      integrated network. In particular, we consider both the generating function
      formalism, valid for degree-uncorrelated networks, and the general case of
      networks with degree correlations. We discuss the different limits of the two
      approaches, indicating the parameter regions where the correlated threshold
      collapses onto the uncorrelated case. Our analytical predictions are confirmed by
      numerical simulations of the model. The temporal percolation concept can be
      fruitfully applied to study epidemic spreading on temporal networks. We show in
      particular how the susceptible-infected-removed model on an activity-driven
      network can be mapped to the percolation problem up to a time given by the
      spreading rate of the epidemic process. This mapping allows us to obtain
      additional information on this process, not available for previous approaches. 

PMID- 24730900
TI  - Cascading failures in networks with proximate dependent nodes.
AB  - We study the mutual percolation of a system composed of two interdependent random
      regular networks. We introduce a notion of distance to explore the effects of the
      proximity of interdependent nodes on the cascade of failures after an initial
      attack. We find a nontrivial relation between the nature of the transition
      through which the networks disintegrate and the parameters of the system, which
      are the degree of the nodes and the maximum distance between interdependent
      nodes. We explain this relation by solving the problem analytically for the
      relevant set of cases. In the process, we solve a variant of Renyi's parking
      problem on treelike graphs. 

PMID- 24730901
TI  - Improving the performance of algorithms to find communities in networks.
AB  - Most algorithms to detect communities in networks typically work without any
      information on the cluster structure to be found, as one has no a priori
      knowledge of it, in general. Not surprisingly, knowing some features of the
      unknown partition could help its identification, yielding an improvement of the
      performance of the method. Here we show that, if the number of clusters was known
      beforehand, standard methods, like modularity optimization, would considerably
      gain in accuracy, mitigating the severe resolution bias that undermines the
      reliability of the results of the original unconstrained version. The number of
      clusters can be inferred from the spectra of the recently introduced
      nonbacktracking and flow matrices, even in benchmark graphs with realistic
      community structure. The limit of such a two-step procedure is the overhead of
      the computation of the spectra. 

PMID- 24730902
TI  - Density-based and transport-based core-periphery structures in networks.
AB  - Networks often possess mesoscale structures, and studying them can yield insights
      into both structure and function. It is most common to study community structure,
      but numerous other types of mesoscale structures also exist. In this paper, we
      examine core-periphery structures based on both density and transport. In such
      structures, core network components are well-connected both among themselves and
      to peripheral components, which are not well-connected to anything. We examine
      core-periphery structures in a wide range of examples of transportation, social,
      and financial networks-including road networks in large urban areas, a rabbit
      warren, a dolphin social network, a European interbank network, and a migration
      network between counties in the United States. We illustrate that a recently
      developed transport-based notion of node coreness is very useful for
      characterizing transportation networks. We also generalize this notion to examine
      core versus peripheral edges, and we show that the resulting diagnostic is also
      useful for transportation networks. To examine the properties of transportation
      networks further, we develop a family of generative models of roadlike networks.
      We illustrate the effect of the dimensionality of the embedding space on
      transportation networks, and we demonstrate that the correlations between
      different measures of coreness can be very different for different types of
      networks. 

PMID- 24730903
TI  - Topological implications of negative curvature for biological and social
      networks.
AB  - Network measures that reflect the most salient properties of complex large-scale
      networks are in high demand in the network research community. In this paper we
      adapt a combinatorial measure of negative curvature (also called hyperbolicity)
      to parametrized finite networks, and show that a variety of biological and social
      networks are hyperbolic. This hyperbolicity property has strong implications on
      the higher-order connectivity and other topological properties of these networks.
      Specifically, we derive and prove bounds on the distance among shortest or
      approximately shortest paths in hyperbolic networks. We describe two implications
      of these bounds to crosstalk in biological networks, and to the existence of
      central, influential neighborhoods in both biological and social networks. 

PMID- 24730904
TI  - Robustness of a partially interdependent network formed of clustered networks.
AB  - Clustering, or transitivity, a behavior observed in real-world networks, affects
      network structure and function. This property has been studied extensively, but
      most of this research has been limited to clustering in single networks. The
      effect of clustering on the robustness of coupled networks, on the other hand,
      has received much less attention. Only the case of a pair of fully coupled
      networks with clustering has recently received study. Here we generalize the
      study of clustering of a fully coupled pair of networks and apply it to a
      partially interdependent network of networks with clustering within the network
      components. We show, both analytically and numerically, how clustering within
      networks affects the percolation properties of interdependent networks, including
      the percolation threshold, the size of the giant component, and the critical
      coupling point at which the first-order phase transition changes to a second
      order phase transition as the coupling between the networks is reduced. We study
      two types of clustering, one proposed by Newman [Phys. Rev. Lett. 103, 058701
      (2009)] in which the average degree is kept constant while the clustering is
      changed, and the other by Hackett et al. [Phys. Rev. E 83, 056107 (2011)] in
      which the degree distribution is kept constant. The first type of clustering is
      studied both analytically and numerically, and the second is studied numerically.

PMID- 24730905
TI  - Promoting collective motion of self-propelled agents by distance-based influence.
AB  - We propose a dynamic model for a system consisting of self-propelled agents in
      which the influence of an agent on another agent is weighted by geographical
      distance. A parameter alpha is introduced to adjust the influence: The smaller
      value of alpha means that the closer neighbors have a stronger influence on the
      moving direction. We find that there exists an optimal value of alpha leading to
      the highest degree of direction consensus. The value of optimal alpha increases
      as the system size increases, while it decreases as the absolute velocity, the
      sensing radius, and the noise amplitude increase. 

PMID- 24730906
TI  - Topological properties and fractal analysis of a recurrence network constructed
      from fractional Brownian motions.
AB  - Many studies have shown that we can gain additional information on time series by
      investigating their accompanying complex networks. In this work, we investigate
      the fundamental topological and fractal properties of recurrence networks
      constructed from fractional Brownian motions (FBMs). First, our results indicate
      that the constructed recurrence networks have exponential degree distributions;
      the average degree exponent <lambda> increases first and then decreases with the
      increase of Hurst index H of the associated FBMs; the relationship between H and
      <lambda> can be represented by a cubic polynomial function. We next focus on the
      motif rank distribution of recurrence networks, so that we can better understand
      networks at the local structure level. We find the interesting superfamily
      phenomenon, i.e., the recurrence networks with the same motif rank pattern being
      grouped into two superfamilies. Last, we numerically analyze the fractal and
      multifractal properties of recurrence networks. We find that the average fractal
      dimension <dB> of recurrence networks decreases with the Hurst index H of the
      associated FBMs, and their dependence approximately satisfies the linear formula
      <dB>~2-H, which means that the fractal dimension of the associated recurrence
      network is close to that of the graph of the FBM. Moreover, our numerical results
      of multifractal analysis show that the multifractality exists in these recurrence
      networks, and the multifractality of these networks becomes stronger at first and
      then weaker when the Hurst index of the associated time series becomes larger
      from 0.4 to 0.95. In particular, the recurrence network with the Hurst index
      H=0.5 possesses the strongest multifractality. In addition, the dependence
      relationships of the average information dimension <D(1)> and the average
      correlation dimension <D(2)> on the Hurst index H can also be fitted well with
      linear functions. Our results strongly suggest that the recurrence network
      inherits the basic characteristic and the fractal nature of the associated FBM
      series. 

PMID- 24730907
TI  - Diverse routes of transition from amplitude to oscillation death in coupled
      oscillators under additional repulsive links.
AB  - We report the existence of diverse routes of transition from amplitude death to
      oscillation death in three different diffusively coupled systems, which are
      perturbed by a symmetry breaking repulsive coupling link. For limit-cycle systems
      the transition is through a pitchfork bifurcation, as has been noted before, but
      in chaotic systems it can be through a saddle-node or a transcritical bifurcation
      depending on the nature of the underlying dynamics of the individual systems. The
      diversity of the routes and their dependence on the complex dynamics of the
      coupled systems not only broadens our understanding of this important phenomenon
      but can lead to potentially new practical applications. 

PMID- 24730908
TI  - Nonlinear Talbot effect of rogue waves.
AB  - Akhmediev and Kuznetsov-Ma breathers are rogue wave solutions of the nonlinear
      Schrodinger equation (NLSE). Talbot effect (TE) is an image recurrence phenomenon
      in the diffraction of light waves. We report the nonlinear TE of rogue waves in a
      cubic medium. It is different from the linear TE, in that the wave propagates in
      a NL medium and is an eigenmode of NLSE. Periodic rogue waves impinging on a NL
      medium exhibit recurrent behavior, but only at the TE length and at the half-TE
      length with a pi-phase shift; the fractional TE is absent. The NL TE is the
      result of the NL interference of the lobes of rogue wave breathers. This
      interaction is related to the transverse period and intensity of breathers, in
      that the bigger the period and the higher the intensity, the shorter the TE
      length. 

PMID- 24730909
TI  - Characteristics of swarms on the edge of fragmentation.
AB  - Fragmentation of particle swarms into isolated subgroups occurs when interaction
      forces are weak or restricted. In the restricted case, the swarm experiences the
      onset of bottlenecks in the graph of interactions that can lead to the
      fragmentation of the system into subgroups. This work investigates the
      characteristics of such bottlenecks when the number of particles in the swarm
      increases. It is shown that certain characteristics of the bottleneck can be
      captured by considering only the number of particles in the swarm. Considering
      the case of a connected communication graph constructed in the hypothesis that
      each particle is influenced by a fixed number of neighboring particles, a limit
      case is determined for which a lower limit to the Cheeger constant can be derived
      analytically without the need for extensive algebraic calculations. Results show
      that as the number of particles increases, the Cheeger constant decreases.
      Although ensuring a minimum number of interactions per particle is sufficient, in
      theory, to ensure cohesion, the swarm may face fragmentation as more particles
      are added to the swarm. 

PMID- 24730910
TI  - Inverse approach to chronotaxic systems for single-variable time series.
AB  - Following the development of a new class of self-sustained oscillators with a
      time-varying but stable frequency, the inverse approach to these systems is now
      formulated. We show how observed data arranged in a single-variable time series
      can be used to recognize such systems. This approach makes use of time-frequency
      domain information using the wavelet transform as well as the recently developed
      method of Bayesian-based inference. In addition, a set of methods, named phase
      fluctuation analysis, is introduced to detect the defining properties of the new
      class of systems by directly analyzing the statistics of the observed
      perturbations.We apply these methods to numerical examples but also elaborate
      further on the cardiac system. 

PMID- 24730911
TI  - Frequency dispersion in the time-delayed Kuramoto model.
AB  - We study the synchronization and frequency distribution in networks of time
      delayed Kuramoto oscillators with identical natural frequency. It is found that a
      pronounced frequency dispersion occurs in networks with nonidentical degree
      distributions. The deviation of the average network frequency from its natural
      frequency, induced by the time delay, is identified as a necessary component for
      this phenomenon. Altogether this results in states intermediate between perfect
      synchronization and complete incoherence. 

PMID- 24730912
TI  - Synchronization in phase-coupled Kuramoto oscillator networks with axonal delay
      and synaptic plasticity.
AB  - We explore both analytically and numerically an ensemble of coupled phase
      oscillators governed by a Kuramoto-type system of differential equations.
      However, we have included the effects of time delay (due to finite signal
      propagation speeds) and network plasticity (via dynamic coupling constants)
      inspired by the Hebbian learning rule in neuroscience. When time delay and
      learning effects combine, interesting synchronization phenomena are observed. We
      investigate the formation of spatiotemporal patterns in both one- and two
      dimensional oscillator lattices with periodic boundary conditions and comment on
      the role of dimensionality. 

PMID- 24730913
TI  - Vectorial velocity filter for ultracold neutrons based on a surface-disordered
      mirror system.
AB  - We perform classical three-dimensional Monte Carlo simulations of ultracold
      neutrons scattering through an absorbing-reflecting mirror system in the Earth's
      gravitational field. We show that the underlying mixed phase space of regular
      skipping motion and random motion due to disorder scattering can be exploited to
      realize a vectorial velocity filter for ultracold neutrons. The absorbing
      reflecting mirror system proposed allows beams of ultracold neutrons with low
      angular divergence to be formed. The range of velocity components can be
      controlled by adjusting the geometric parameters of the system. First
      experimental tests of its performance are presented. One potential future
      application is the investigation of transport and scattering dynamics in confined
      systems downstream of the filter. 

PMID- 24730914
TI  - Hydrodynamic instability of thermal fronts in reactive porous media: spinning
      patterns.
AB  - The interaction of convection and reaction front propagation is known to exhibit
      a nonlinear phenomenons in the case of an adverse flow, i.e., when the gas
      velocity (V=[u,v]') and the front velocity (Vf) are of opposite directions. This
      was demonstrated both experimentally and analytically under isothermal conditions
      with Vf constant independent of V. Here we analyze thermal reaction front
      propagation in a porous medium in which an exothermic reaction of Arrhenius
      kinetics occurs. Numerical simulations of a packed-bed reactor model accounting
      for variable temperature, concentration, and hydrodynamic fields following the
      Euler-Darcy equations revealed emergence of spinning transversal patterns. Such
      solution cannot emerge in a two-variable (C,T) model, assuming "frozen"
      hydrodynamics, within a feasible domain of parameters. Two models are employed
      for analysis: a qualitative model based on a learning one-tube and two-tube
      consideration and an extended Landau-Darries instability analysis to account for
      the momentum losses and for a variable front propagation velocity. Both models
      revealed the important role of the Vf(u) dependence which can be presented as
      Vf=u-Vch, where the chemical component of the front velocity (Vch) depends on the
      main governing parameters such as the adiabatic temperature rise (DeltaTa) and
      the inlet velocity (uin). The instability takes place if the parameter
      beta=?Vch/?u<1. The effect of DeltaTa, uin on the instability domain obtained in
      simulations can be translated to the effect of the parameter beta. 

PMID- 24730915
TI  - Scattering experiments with microwave billiards at an exceptional point under
      broken time-reversal invariance.
AB  - Scattering experiments with microwave cavities were performed and the effects of
      broken time-reversal invariance (TRI), induced by means of a magnetized ferrite
      placed inside the cavity, on an isolated doublet of nearly degenerate resonances
      were investigated. All elements of the effective Hamiltonian of this two-level
      system were extracted. As a function of two experimental parameters, the doublet
      and the associated eigenvectors could be tuned to coalesce at a so-called
      exceptional point (EP). The behavior of the eigenvalues and eigenvectors when
      encircling the EP in parameter space was studied, including the geometric
      amplitude that builds up in the case of broken TRI. A one-dimensional subspace of
      parameters was found where the differences of the eigenvalues are either real or
      purely imaginary. There, the Hamiltonians were found to be PT invariant under the
      combined operation of parity (P) and time reversal (T) in a generalized sense.
      The EP is the point of transition between both regions. There a spontaneous
      breaking of PT occurs. 

PMID- 24730916
TI  - Fundamental- and first-order localized states in a cubic-quintic reaction
      diffusion system.
AB  - This article analyzes the properties of rotationally symmetric self-localized
      solutions with different radial quantum numbers in the simplest one- and two
      component reaction-diffusion systems. The consideration is made in one and two
      dimensions with the focus on the fundamental and first higher-order solutions
      showing zero and one intersections of the radial profile with zero. It is
      demonstrated that the solution with one intersection does not exist for the case
      of the quadratic-cubic nonlinearity, while the cubic-quintic extension of the
      models does allow existence. I show additionally that the cubic-quintic reaction
      diffusion system supports the existence and stability of the states with zero
      quantum numbers, as well as their antistates, state-antistate pairs, and
      clusters, which can be interpreted as the states with nonzero azimuthal quantum
      number. 

PMID- 24730917
TI  - Resonances and poles in isoscattering microwave networks and graphs.
AB  - Can one hear the shape of a graph? This is a modification of the famous question
      of Mark Kac "Can one hear the shape of a drum?" which can be asked in the case of
      scattering systems such as quantum graphs and microwave networks. It addresses an
      important mathematical problem whether scattering properties of such systems are
      uniquely connected to their shapes? Recent experimental results based on a
      characteristics of graphs such as the cumulative phase of the determinant of the
      scattering matrices indicate a negative answer to this question [O. Hul, M.
      Lawniczak, S. Bauch, A. Sawicki, M. Kus, and L. Sirko, Phys. Rev. Lett. 109,
      040402 (2012)]. In this paper we consider important local characteristics of
      graphs such as structures of resonances and poles of the determinant of the
      scattering matrices. Using these characteristics we study experimentally and
      theoretically properties of graphs and directly confirm that the pair of graphs
      considered in the cited paper is isoscattering. The experimental results are
      compared to the theoretical ones for a broad frequency range from 0.01 to 3 GHz.
      In the numerical calculations of the resonances of the graphs absorption present
      in the experimental networks is taken into account. 

PMID- 24730918
TI  - Optimized spectral estimation for nonlinear synchronizing systems.
AB  - In many fields of research nonlinear dynamical systems are investigated. When
      more than one process is measured, besides the distinct properties of the
      individual processes, their interactions are of interest. Often linear methods
      such as coherence are used for the analysis. The estimation of coherence can lead
      to false conclusions when applied without fulfilling several key assumptions. We
      introduce a data driven method to optimize the choice of the parameters for
      spectral estimation. Its applicability is demonstrated based on analytical
      calculations and exemplified in a simulation study. We complete our investigation
      with an application to nonlinear tremor signals in Parkinson's disease. In
      particular, we analyze electroencephalogram and electromyogram data. 

PMID- 24730919
TI  - Nonlinear time series analysis and clustering for jet axis identification in
      vertical turbulent heated jets.
AB  - In the present work we approach the hydrodynamic problem of discriminating the
      state of the turbulent fluid region as a function of the distance from the axis
      of a turbulent jet axis. More specifically, we analyzed temperature fluctuations
      in vertical turbulent heated jets where temperature time series were recorded
      along a horizontal line through the jet axis. We employed data from different
      sets of experiments with various initial conditions out of circular and
      elliptical shaped nozzles in order to identify time series taken at the jet axis,
      and discriminate them from those taken near the boundary with ambient fluid using
      nonconventional hydrodynamics methods. For each temperature time series measured
      at a different distance from jet axis, we estimated mainly nonlinear measures
      such as mutual information combined with descriptive statistics measures, as well
      as some linear and nonlinear dynamic detectors such as Hurst exponent, detrended
      fluctuation analysis, and Hjorth parameters. The results obtained in all cases
      have shown that the proposed methodology allows us to distinguish the flow regime
      around the jet axis and identify the time series corresponding to the jet axis in
      agreement with the conventional statistical hydrodynamic method. Furthermore, in
      order to reject the null hypothesis that the time series originate from a
      stochastic process, we applied the surrogate data method. 

PMID- 24730920
TI  - Rogue wave modes for a derivative nonlinear Schrodinger model.
AB  - Rogue waves in fluid dynamics and optical waveguides are unexpectedly large
      displacements from a background state, and occur in the nonlinear Schrodinger
      equation with positive linear dispersion in the regime of positive cubic
      nonlinearity. Rogue waves of a derivative nonlinear Schrodinger equation are
      calculated in this work as a long-wave limit of a breather (a pulsating mode),
      and can occur in the regime of negative cubic nonlinearity if a sufficiently
      strong self-steepening nonlinearity is also present. This critical magnitude is
      shown to be precisely the threshold for the onset of modulation instabilities of
      the background plane wave, providing a strong piece of evidence regarding the
      connection between a rogue wave and modulation instability. The maximum amplitude
      of the rogue wave is three times that of the background plane wave, a result
      identical to that of the Peregrine breather in the classical nonlinear
      Schrodinger equation model. This amplification ratio and the resulting spectral
      broadening arising from modulation instability correlate with recent experimental
      results of water waves. Numerical simulations in the regime of marginal stability
      are described. 

PMID- 24730921
TI  - Amplitude death in oscillator networks with variable-delay coupling.
AB  - We study the conditions of amplitude death in a network of delay-coupled limit
      cycle oscillators by including time-varying delay in the coupling and self
      feedback. By generalizing the master stability function formalism to include
      variable-delay connections with high-frequency delay modulations (i.e., the
      distributed-delay limit), we analyze the regimes of amplitude death in a ring
      network of Stuart-Landau oscillators and demonstrate the superiority of the
      proposed method with respect to the constant delay case. The possibility of
      stabilizing the steady state is restricted by the odd-number property of the
      local node dynamics independently of the network topology and the coupling
      parameters. 

PMID- 24730922
TI  - Multiscale multifractal analysis of traffic signals to uncover richer structures.
AB  - Multifractal detrended fluctuation analysis (MF-DFA) is the most popular method
      to detect multifractal characteristics of considerable signals such as traffic
      signals. When fractal properties vary from point to point along the series, it
      leads to multifractality. In this study, we concentrate not only on the fact that
      traffic signals have multifractal properties, but also that such properties
      depend on the time scale in which the multifractality is computed. Via the
      multiscale multifractal analysis (MMA), traffic signals appear to be far more
      complex and contain more information which MF-DFA cannot explore by using a fixed
      time scale. More importantly, we do not have to avoid data sets with crossovers
      or narrow the investigated time scales, which may lead to biased results.
      Instead, the Hurst surface provides a spectrum of local scaling exponents at
      different scale ranges, which helps us to easily position these crossovers.
      Through comparing Hurst surfaces for signals before and after removing periodical
      trends, we find periodicities of traffic signals are the main source of the
      crossovers. Besides, the Hurst surface of the weekday series behaves differently
      from that of the weekend series. Results also show that multifractality of
      traffic signals is mainly due to both broad probability density function and
      correlations. The effects of data loss are also discussed, which suggests that we
      should carefully handle MMA results when the percentage of data loss is larger
      than 40%. 

PMID- 24730923
TI  - Transition to synchronization in a Kuramoto model with the first- and second
      order interaction terms.
AB  - We investigate a Kuramoto model incorporated with the first-order and the second
      order interaction terms. We show that the model displays the coexistence of
      multiattractors and different attractors may be characterized by the phase
      distributions of oscillators. By investigating the transition diagrams in both
      forward continuation and backward continuation, we find that the synchronous
      state with unimodal phase distribution is the most stable one while the state in
      cluster synchrony with evenly distributed bimodal phase distribution is the least
      stable one. We also present the phase diagram of the model in the parameter
      space. 

PMID- 24730924
TI  - Finite-time Lyapunov exponents in time-delayed nonlinear dynamical systems.
AB  - We introduce a method for the calculation of finite-time Lyapunov exponents in
      time-delayed nonlinear dynamical systems. We apply the method to the Mackey-Glass
      model with time-delayed feedback. We investigate the standard deviation of the
      probability distribution of the finite-time Lyapunov exponents when the finite
      time or the delay time is changed. It is found that the standard deviation
      decreases in a power-law scaling with the exponent ~0.5 as the finite time or the
      delay time is increased. Similar results are obtained for the finite-time
      Lyapunov spectrum. 

PMID- 24730925
TI  - Multistabilities and symmetry-broken one-color and two-color states in closely
      coupled single-mode lasers.
AB  - We theoretically investigate the dynamics of two mutually coupled, identical
      single-mode semi-conductor lasers. For small separation and large coupling
      between the lasers, symmetry-broken one-color states are shown to be stable. In
      this case the light outputs of the lasers have significantly different
      intensities while at the same time the lasers are locked to a single common
      frequency. For intermediate coupling we observe stable symmetry-broken two-color
      states, where both lasers lase simultaneously at two optical frequencies which
      are separated by up to 150 GHz. Using a five-dimensional model, we identify the
      bifurcation structure which is responsible for the appearance of symmetric and
      symmetry-broken one-color and two-color states. Several of these states give rise
      to multistabilities and therefore allow for the design of all-optical memory
      elements on the basis of two coupled single-mode lasers. The switching
      performance of selected designs of optical memory elements is studied
      numerically. 

PMID- 24730926
TI  - Creation of two-dimensional composite solitons in spin-orbit-coupled self
      attractive Bose-Einstein condensates in free space.
AB  - It is commonly known that two-dimensional mean-field models of optical and matter
      waves with cubic self-attraction cannot produce stable solitons in free space
      because of the occurrence of collapse in the same setting. By means of numerical
      analysis and variational approximation, we demonstrate that the two-component
      model of the Bose-Einstein condensate with the spin-orbit Rashba coupling and
      cubic attractive interactions gives rise to solitary-vortex complexes of two
      types: semivortices (SVs, with a vortex in one component and a fundamental
      soliton in the other), and mixed modes (MMs, with topological charges 0 and +/-1
      mixed in both components). These two-dimensional composite modes can be created
      using the trapping harmonic-oscillator (HO) potential, but remain stable in free
      space, if the trap is gradually removed. The SVs and MMs realize the ground state
      of the system, provided that the self-attraction in the two components is,
      respectively, stronger or weaker than the cross attraction between them. The SVs
      and MMs which are not the ground states are subject to a drift instability. In
      free space (in the absence of the HO trap), modes of both types degenerate into
      unstable Townes solitons when their norms attain the respective critical values,
      while there is no lower existence threshold for the stable modes. Moving free
      space stable solitons are also found in the present non-Galilean-invariant
      system, up to a critical velocity. Collisions between two moving solitons lead to
      their merger into a single one. 

PMID- 24730927
TI  - Finite-time synchronization of tunnel-diode-based chaotic oscillators.
AB  - This paper addresses the problem of finite-time synchronization of tunnel diode
      based chaotic oscillators. After a brief investigation of its chaotic dynamics,
      we propose an active adaptive feedback coupling which accomplishes the
      synchronization of tunnel-diode-based chaotic systems with and without the
      presence of delay(s), basing ourselves on Lyapunov and on Krasovskii-Lyapunov
      stability theories. This feedback coupling could be applied to many other chaotic
      systems. A finite horizon can be arbitrarily established by ensuring that chaos
      synchronization is achieved at a pre-established time. An advantage of the
      proposed feedback coupling is that it is simple and easy to implement. Both
      mathematical investigations and numerical simulations followed by pspice
      experiment are presented to show the feasibility of the proposed method. 

PMID- 24730928
TI  - Temporal flooding of regular islands by chaotic wave packets.
AB  - We investigate the time evolution of wave packets in systems with a mixed phase
      space where regular islands and chaotic motion coexist. For wave packets started
      in the chaotic sea on average the weight on a quantized torus of the regular
      island increases due to dynamical tunneling. This flooding weight initially
      increases linearly and saturates to a value which varies from torus to torus. We
      demonstrate for the asymptotic flooding weight universal scaling with an
      effective tunneling coupling for quantum maps and the mushroom billiard. This
      universality is reproduced by a suitable random matrix model. 

PMID- 24730929
TI  - Minimal model dynamics for twelvefold quasipatterns.
AB  - A dynamical model of the Swift-Hohenberg type is proposed to describe the
      formation of twelvefold quasipattern as observed, for instance, in optical
      systems. The model incorporates the general mechanisms leading to quasipattern
      formation and does not need external forcing to generate them. Besides quadratic
      nonlinearities, the model takes into account an angular dependence of the
      nonlinear couplings between spatial modes with different orientations.
      Furthermore, the marginal stability curve presents other local minima than the
      one corresponding to critical modes, as usual in optical systems. Quasipatterns
      form when one of these secondary minima may be associated with harmonics built on
      pairs of critical modes. The model is analyzed numerically and in the framework
      of amplitude equations. The results confirm the importance of harmonics to
      stabilize quasipatterns and assess the applicability of the model to other
      systems with similar generic properties. 

PMID- 24730930
TI  - Damped-driven granular chains: an ideal playground for dark breathers and
      multibreathers.
AB  - By applying an out-of-phase actuation at the boundaries of a uniform chain of
      granular particles, we demonstrate experimentally that time-periodic and
      spatially localized structures with a nonzero background (so-called dark
      breathers) emerge for a wide range of parameter values and initial conditions. We
      demonstrate a remarkable control over the number of breathers within the
      multibreather pattern that can be "dialed in" by varying the frequency or
      amplitude of the actuation. The values of the frequency (or amplitude) where the
      transition between different multibreather states occurs are predicted accurately
      by the proposed theoretical model, which is numerically shown to support exact
      dark breather and multibreather solutions. Moreover, we visualize detailed
      temporal and spatial profiles of breathers and, especially, of multibreathers
      using a full-field probing technology and enable a systematic favorable
      comparison among theory, computation, and experiments. A detailed bifurcation
      analysis reveals that the dark and multibreather families are connected in a
      "snaking" pattern, providing a roadmap for the identification of such fundamental
      states and their bistability in the laboratory. 

PMID- 24730931
TI  - Jittery velocity relaxation of an elastic sphere immersed in a viscous
      incompressible fluid.
AB  - Velocity relaxation of an elastic sphere immersed in a viscous incompressible
      fluid is studied on the basis of the equations of linear elasticity and the
      linearized Navier-Stokes equations. It is found that both translational motion
      after a sudden impulse and rotational motion after a sudden twist show jittery
      behavior in the long-time regime, with many reversals of velocity if the sphere
      is sufficiently flexible. In the extreme long-time regime the translational and
      rotational velocity relaxation functions each decay with a universal algebraic
      long-time tail. The added mass and the added moment of inertia of the sphere are
      found to vanish. 

PMID- 24730932
TI  - Transition to two-dimensionality in magnetohydrodynamic turbulent Taylor-Couette
      flow.
AB  - Transition from a Taylor-Couette turbulent flow to a completely two-dimensional
      axisymmetric turbulent state is realized numerically by increasing gradually the
      strength of the azimuthal magnetic field produced by electric current flowing
      through the axial rod. With the increase of the Hartmann number, the Taylor
      vortex-like structures shrink, move closer to the inner cylinder, and turn into
      unsteady but perfect tori at sufficiently high Hartmann numbers. 

PMID- 24730933
TI  - Zero absolute vorticity: insight from experiments in rotating laminar plane
      Couette flow.
AB  - For pressure-driven turbulent channel flows undergoing spanwise system rotation,
      it has been observed that the absolute vorticity, i.e., the sum of the averaged
      spanwise flow vorticity and system rotation, tends to zero in the central region
      of the channel. This observation has so far eluded a convincing theoretical
      explanation, despite experimental and numerical evidence reported in the
      literature. Here we show experimentally that three-dimensional laminar structures
      in plane Couette flow, which appear under anticyclonic system rotation, give the
      same effect, namely, that the absolute vorticity tends to zero if the rotation
      rate is high enough. It is shown that this is equivalent to a local Richardson
      number of approximately zero, which would indicate a stable condition. We also
      offer an explanation based on Kelvin's circulation theorem to demonstrate that
      the absolute vorticity should remain constant and approximately equal to zero in
      the central region of the channel when going from the nonrotating fully turbulent
      state to any state with sufficiently high rotation. 

PMID- 24730934
TI  - Effect of confinement on the deformation of microfluidic drops.
AB  - We study the deformation of drops squeezed between the floor and ceiling of a
      microchannel and subjected to a hyperbolic flow. We observe that the maximum
      deformation of drops depends on both the drop size and the rate of strain of the
      external flow and can be described with power laws with exponents 2.59+/-0.28 and
      0.91+/-0.05, respectively. We develop a theoretical model to describe the
      deformation of squeezed drops based on the Darcy approximation for shallow
      geometries and the use of complex potentials. The model describes the steady
      state deformation of the drops as a function of a nondimensional parameter
      Cadelta2, where Ca is the capillary number (proportional to the strain rate and
      the drop size) and delta is a confinement parameter equal to the drop size
      divided by the channel height. For small deformations, the theoretical model
      predicts a linear relationship between the deformation of drops and this
      parameter, in good agreement with the experimental observations. 

PMID- 24730935
TI  - Preferred location of droplet collisions in turbulent flows.
AB  - This study investigates the local flow characteristics near droplet-droplet
      collisions by means of direct numerical simulation of isotropic cloudlike
      turbulence. The key finding is that, generally, droplets do not collide where
      they preferentially concentrate. Preferential concentration is found to happen as
      expected in regions of low enstrophy (vorticity magnitude), but collisions tend
      to take place in regions with significantly higher dissipation rates (up to a
      factor of 2.5 for Stokes unity droplets). Investigation of the droplet history
      reveals that collisions are consistently preceded by dissipative events. Based on
      the droplet history data, the following physical picture of a collision can be
      constructed: Enstrophy makes droplets preferentially concentrate in quiescent
      flow regions, thereby increasing the droplet velocity coherence, i.e., decreasing
      relative velocities between droplets. Strongly clustered droplets thus have a low
      collision probability, until a dissipative event accelerates the droplets towards
      each other. We study the relation between the local dissipation rate and the
      local collision kernel and vary the averaging scale to relate the results to the
      globally averaged collision and dissipation rates. It is noted that, unlike
      enstrophy, there is a positive correlation between the dissipation rate and
      collision efficiency that extends from the largest to the smallest scales of the
      flow. 

PMID- 24730936
TI  - Acceleration statistics in thermally driven superfluid turbulence.
AB  - New methods of flow visualization near absolute zero have opened the way to
      directly compare quantum turbulence (in superfluid helium) to classical
      turbulence (in ordinary fluids such as air or water) and explore analogies and
      differences. We present results of numerical simulations in which we examine the
      statistics of the superfluid acceleration in thermal counterflow. We find that,
      unlike the velocity, the acceleration obeys scaling laws similar to classical
      turbulence, in agreement with a recent quantum turbulence experiment of La Mantia
      et al. 

PMID- 24730937
TI  - Electro-osmotic flow in disordered porous and fractured media.
AB  - Electro-osmosis phenomena are studied in a two-dimensional (2D) model disordered
      porous medium. The flow passages are represented by a network of spatially
      distributed rectangular channels with random orientations. The channels may
      represent microfractures in fractured porous media or in a network of
      interconnected microfractures, pores in a porous medium, or fibers in a fibrous
      porous material. The linearized equations of electrokinetics are solved
      numerically in a single channel, and in the 2D network of the channels. The
      macroscopic electrical conductivity sigma and electro-osmotic coupling
      coefficient beta are computed as functions of the electrical surface potential
      zeta and such geometrical parameters of the network as the channels' number
      density and widths, as well as the porosity of the medium. Despite the complexity
      of the phenomena and the model of porous media that is used, both sigma and beta
      appear to depend on the characteristics of the phenomena and porous media through
      very simple relations. 

PMID- 24730938
TI  - Nonlinear energy transfers and phase diagrams for geostrophically balanced
      rotating-stratified flows.
AB  - Equilibrium statistical mechanics tools have been developed to obtain indications
      about the natural tendencies of nonlinear energy transfers in two-dimensional and
      quasi-two-dimensional flows like rotating and stratified flows in geostrophic
      balance. In this article we consider a simple model of such flows with a
      nontrivial vertical structure, namely, two-layer quasigeostrophic flows, which
      remain amenable to analytical study. We obtain the statistical equilibria of the
      system in the case of a linear vorticity-stream function relation, build the
      corresponding phase diagram, and discuss the most probable outcome of nonlinear
      energy transfers, both on the horizontal and on the vertical, in the presence of
      stratification and rotation. 

PMID- 24730939
TI  - alpha effect in a turbulent liquid-metal plane Couette flow.
AB  - We calculate the mean electromotive force in plane Couette flows of a nonrotating
      conducting fluid under the influence of a large-scale magnetic field for driven
      turbulence. A vertical stratification of the turbulence intensity results in an
      alpha effect owing to the presence of horizontal shear. Here we discuss the
      possibility of an experimental determination of the components of the alpha
      tensor using both quasilinear theory and nonlinear numerical simulations. For
      magnetic Prandtl numbers of the order of unity, we find that in the high
      conductivity limit the alpha effect in the direction of the flow clearly exceeds
      the component in spanwise direction. In this limit, alpha runs linearly with the
      magnetic Reynolds number Rm, while in the low-conductivity limit it runs with the
      product Rm.Re, where Re is the kinetic Reynolds number, so that for a given Rm
      the alpha effect grows with decreasing magnetic Prandtl number. For the small
      magnetic Prandtl numbers of liquid metals, a common value for the horizontal
      elements of the alpha tensor appears, which makes it unimportant whether the
      alpha effect is measured in the spanwise or the streamwise directions. The
      resulting effect should lead to an observable voltage of about 0.5 mV in both
      directions for magnetic fields of 1 kG and velocity fluctuations of about 1 m/s
      in a channel of 50-cm height (independent of its width). 

PMID- 24730940
TI  - Electrohydrodynamic instability in an annular liquid layer with radial
      conductivity gradients.
AB  - In this paper, the electrohydrodynamic stability in an annular liquid layer with
      a radial electrical conductivity gradient is investigated. A weak shear flow
      arises from a constant pressure gradient in the axial direction. In the radial
      direction, an electric field is applied. The three-dimensional linear instability
      analysis is implemented to study the influence of the inner radius, electrical
      conductivity gradient, shear flow, and ionic diffusion on the dynamics of the
      fluid layer. It is found that the critical unstable mode may either be
      oscillatory or stationary. The system becomes more unstable as the dimensionless
      inner radius a increases. When the inner radius a is small, the critical unstable
      mode is stationary, while it is given by three-dimensional oblique waves when a
      is large. When the conductivity gradient is small, the critical unstable mode is
      the three-dimensional oblique wave, while when the conductivity gradient is
      large, it would switch to the stationary mode rather than the oscillatory mode.
      The system becomes more unstable when the Reynolds number is slightly increased
      from zero. Additionally, it is found that the electrical Schmidt number has dual
      effects. The liquid layer becomes either more unstable or stable as the electric
      Schmidt number increases. 

PMID- 24730941
TI  - Numerical simulations of electrostatically driven jets from nonviscous droplets.
AB  - The evolution of a perfectly conducting and nonviscous fluid, under the action of
      an electric field (uniform at infinity), is studied numerically. Level set
      techniques are employed to develop an Eulerian potential flow model that can
      follow the drop evolution past breakup, while the free surface fluid velocity and
      the electric field force are obtained via axisymmetric boundary integral
      calculations. Numerical results are presented for neutral and charged droplets
      and for free charged droplets. In all cases, the evolution droplet aspect ratio,
      progeny droplet size, Taylor cone angles, jet shapes, and self-similar scaling
      exponents are reported. In particular, for free charged water droplets, the
      bursting frequency and other jetting characteristics have been carefully
      analyzed. Wherever possible, these results are compared with previously reported
      experiments and simulations. 

PMID- 24730942
TI  - Superadiabatic evolution of acoustic and vorticity perturbations in Couette flow.
AB  - Nonadiabatic transitions between the acoustic and the vorticity modes perturbing
      a plane Couette flow are examined in the context of higher-order WKB asymptotics.
      In the case of the Schrodinger equation, it is known that looking at the solution
      expressed in the superadiabatic base, composed of higher-order asymptotic
      solutions, smoothes quantum state transitions. Then, increasing the order of the
      superadiabatic base causes these transitions to tend to the Gauss error function,
      and, once an optimal order is reached, the asymptotic process starts to diverge.
      We show that for perturbations in Couette flow, similar results can be applied on
      the amplitudes of the vorticity and acoustic modes. This allows us to more
      closely track the emergence of the acoustic modes in the presence of the
      vorticity mode. 

PMID- 24730943
TI  - Small-scale anisotropic intermittency in magnetohydrodynamic turbulence at low
      magnetic Reynolds numbers.
AB  - Small-scale anisotropic intermittency is examined in three-dimensional
      incompressible magnetohydrodynamic turbulence subjected to a uniformly imposed
      magnetic field. Orthonormal wavelet analyses are applied to direct numerical
      simulation data at moderate Reynolds number and for different interaction
      parameters. The magnetic Reynolds number is sufficiently low such that the
      quasistatic approximation can be applied. Scale-dependent statistical measures
      are introduced to quantify anisotropy in terms of the flow components, either
      parallel or perpendicular to the imposed magnetic field, and in terms of the
      different directions. Moreover, the flow intermittency is shown to increase with
      increasing values of the interaction parameter, which is reflected in strongly
      growing flatness values when the scale decreases. The scale-dependent anisotropy
      of energy is found to be independent of scale for all considered values of the
      interaction parameter. The strength of the imposed magnetic field does amplify
      the anisotropy of the flow. 

PMID- 24730944
TI  - Influence of the angle between the wind and the isothermal surfaces on the
      boundary layer structures in turbulent thermal convection.
AB  - We derive the asymptotes for the ratio of the thermal to viscous boundary layer
      thicknesses for infinite and infinitesimal Prandtl numbers Pr as functions of the
      angle beta between the large-scale circulation and an isothermal heated or cooled
      surface for the case of turbulent thermal convection with laminar-like boundary
      layers. For this purpose, we apply the Falkner-Skan ansatz, which is a
      generalization of the Prandtl-Blasius one to a nonhorizontal free-stream flow
      above the viscous boundary layer. Based on our direct numerical simulations (DNS)
      of turbulent Rayleigh-Benard convection for Pr=0.1, 1, and 10 and moderate
      Rayleigh numbers up to 108 we evaluate the value of beta that is found to be
      around 0.7pi for all investigated cases. Our theoretical predictions for the
      boundary layer thicknesses for this beta and the considered Pr are in good
      agreement with the DNS results. 

PMID- 24730945
TI  - Streamline segment statistics of premixed flames with nonunity Lewis numbers.
AB  - The interaction of flame and surrounding fluid motion is of central importance in
      the fundamental understanding of turbulent combustion. It is demonstrated here
      that this interaction can be represented using streamline segment analysis, which
      was previously applied in nonreactive turbulence. The present work focuses on the
      effects of the global Lewis number (Le) on streamline segment statistics in
      premixed flames in the thin-reaction-zones regime. A direct numerical simulation
      database of freely propagating thin-reaction-zones regime flames with Le ranging
      from 0.34 to 1.2 is used to demonstrate that Le has significant influences on the
      characteristic features of the streamline segment, such as the curve length, the
      difference in the velocity magnitude at two extremal points, and their
      correlations with the local flame curvature. The strengthenings of the dilatation
      rate, flame normal acceleration, and flame-generated turbulence with decreasing
      Le are principally responsible for these observed effects. An expression for the
      probability density function (pdf) of the streamline segment length, originally
      developed for nonreacting turbulent flows, captures the qualitative behavior for
      turbulent premixed flames in the thin-reaction-zones regime for a wide range of
      Le values. The joint pdfs between the streamline length and the difference in the
      velocity magnitude at two extremal points for both unweighted and density
      weighted velocity vectors are analyzed and compared. Detailed explanations are
      provided for the observed differences in the topological behaviors of the
      streamline segment in response to the global Le. 

PMID- 24730946
TI  - Bulk stress distributions in the pore space of sphere-packed beds under Darcy
      flow conditions.
AB  - In this paper, bulk stress distributions in the pore space of columns packed with
      spheres are numerically computed with lattice Boltzmann simulations. Three
      different ideally packed and one randomly packed configuration of the columns are
      considered under Darcy flow conditions. The stress distributions change when the
      packing type changes. In the Darcy regime, the normalized stress distribution for
      a particular packing type is independent of the pressure difference that drives
      the flow and presents a common pattern. The three parameter (3P) log-normal
      distribution is found to describe the stress distributions in the randomly packed
      beds within statistical accuracy. In addition, the 3P log-normal distribution is
      still valid when highly porous scaffold geometries rather than sphere beds are
      examined. It is also shown that the 3P log-normal distribution can describe the
      bulk stress distribution in consolidated reservoir rocks like Berea sandstone. 

PMID- 24730947
TI  - Concentration dependence of nanochannel impedance and the determination of
      surface charge.
AB  - In this paper, we demonstrate the variation of nanochannel impedance with bulk
      (reservoir) electrolyte concentration. The impedance of a nanochannel is shown to
      correspond to a characteristic deformed semicircular arc. The degree of
      deformation decreases with increasing concentration, and at a sufficiently low
      concentration the complex impedance saturates, becoming essentially independent
      of the reservoir concentration. This behavior is indicative of a surface
      conduction dominant regime. Here we demonstrate that this effect extends beyond
      dc conductance and affects the ac response of the system as well, including both
      phase relationship and magnitude. The nanochannel resistance, obtained from low
      voltage ac measurements, is then used to extract the nanochannel surface charge
      density. This is found to increase in magnitude with increasing electrolyte
      concentration. 

PMID- 24730948
TI  - Numerical simulations of the Richtmyer-Meshkov instability in solid-vacuum
      interfaces using calibrated plasticity laws.
AB  - The Richtmyer-Meshkov instability of interfaces separating elastic-plastic
      materials from vacuum (heavy-light configuration) is studied by means of
      computational techniques. A fully Eulerian multimaterial algorithm that solves
      consistently the Euler equations and the time evolution of the deformations in
      the material is applied to three distinct materials (copper, aluminum, and
      stainless steel). If a perfectly plastic constitutive relation is considered, an
      empirical law is computed that relates the long-term perturbation amplitude of
      the interface, its maximum growth rate, the initial density, and the yield stress
      of the material. It is shown that this linear relation can be extended to
      materials that follow more complex plastic behavior which can account for rate
      dependency, hardening, and thermal softening, and to situations in which small
      perturbation theory is no longer valid. In effect, the yield stress computed from
      measurements of the long-term amplitude and maximum growth rate closely matches
      the von Mises stress found at the interface of solid materials for a wide range
      of cases with different initial parameters. 

PMID- 24730949
TI  - Gas flow in plant microfluidic networks controlled by capillary valves.
AB  - The xylem vessels of trees constitute a model natural microfluidic system. In
      this work, we have studied the mechanism of air flow in the Populus xylem. The
      vessel microstructure was characterized by optical microscopy, transmission
      electronic microscopy (TEM), and atomic force microscopy (AFM) at different
      length scales. The xylem vessels have length ~15 cm and diameter ~20MUm. Flow
      from one vessel to the next occurs through ~102 pits, which are grouped together
      at the ends of the vessels. The pits contain a thin, porous pit membrane with a
      thickness of 310 nm. We have measured the Young's moduli of the vessel wall and
      of the pits (both water-saturated and after drying) by specific nanoindentation
      and nanoflexion experiments with AFM. We found that both the dried and water
      saturated pit membranes have Young's modulus around 0.4 MPa, in agreement with
      values obtained by micromolding of pits deformed by an applied pressure
      difference. Air injection experiments reveal that air flows through the xylem
      vessels when the differential pressure across a sample is larger than a critical
      value DeltaPc=1.8 MPa. In order to model the air flow rate for DeltaP?DeltaPc, we
      assumed the pit membrane to be a porous medium that is strained by the applied
      pressure difference. Water menisci in the pit pores play the role of capillary
      valves, which open at DeltaP=DeltaPc. From the point of view of the plant
      physiology, this work presents a basic understanding of the physics of bordered
      pits. 

PMID- 24730950
TI  - Towards modeling of nonlinear laser-plasma interactions with hydrocodes: the
      thick-ray approach.
AB  - This paper deals with the computation of laser beam intensity in large-scale
      radiative hydrocodes applied to the modeling of nonlinear laser-plasma
      interactions (LPIs) in inertial confinement fusion (ICF). The paraxial complex
      geometrical optics (PCGO) is adapted for light waves in an inhomogeneous medium
      and modified to include the inverse bremsstrahlung absorption and the
      ponderomotive force. This thick-ray model is compared to the standard ray-tracing
      (RT) approach, both in the chic code. The PCGO model leads to different power
      deposition patterns and better diffraction modeling compared to standard RT
      codes. The intensity-reconstruction technique used in RT codes to model nonlinear
      LPI leads to artificial filamentation and fails to reproduce realistic
      ponderomotive self-focusing distances, intensity amplifications, and density
      channel depletions, whereas PCGO succeeds. Bundles of Gaussian thick rays can be
      used to model realistic non-Gaussian ICF beams. The PCGO approach is expected to
      improve the accuracy of ICF simulations and serve as a basis to implement diverse
      LPI effects in large-scale hydrocodes. 

PMID- 24730951
TI  - Dielectric function of a collisional plasma for arbitrary ionic charge.
AB  - A simple model for the dielectric function of a completely ionized plasma with an
      arbitrary ionic charge that is valid for long-wavelength high-frequency
      perturbations is derived using an approximate solution of a linearized Fokker
      Planck kinetic equation for electrons with a Landau collision integral. The model
      accounts for both the electron-ion collisions and the collisions of the
      subthermal (cold) electrons with thermal ones. The relative contribution of the
      latter collisions to the dielectric function is treated phenomenologically,
      introducing some parameter kappa that is chosen in such a way as to get a well
      known expression for stationary electric conductivity in the low-frequency region
      and fulfill the requirement of a vanishing contribution of electron-electron
      collisions in the high-frequency region. This procedure ensures the applicability
      of our model in a wide range of plasma parameters as well as the frequency of the
      electromagnetic radiation. Unlike the interpolation formula proposed earlier by
      Brantov et al. [Brantov et al., JETP 106, 983 (2008)], our model fulfills the
      Kramers-Kronig relations and permits a generalization for the cases of degenerate
      and strongly coupled plasmas. With this in mind, a generalization of the well
      known Lee-More model [Y. T. Lee and R. M. More, Phys. Fluids 27, 1273 (1984)] for
      stationary conductivity and its extension to dynamical conductivity [O. F.
      Kostenko and N. E. Andreev, GSI Annual Report No. GSI-2008-2, 2008 (unpublished),
      p. 44] is proposed for the case of plasmas with arbitrary ionic charge. 

PMID- 24730952
TI  - Influence of many-body interactions during the ionization of gases by short
      intense optical pulses.
AB  - The excitation of atomic gases by short high-intensity optical pulses leads to
      significant electron ionization. In dilute systems, the generated distribution of
      ionized electrons is highly anisotropic, reflecting the quantum mechanical
      properties of the atomic states involved in the many photon transitions. For
      higher atomic densities, the Coulomb interaction in the electron-ion system leads
      to the development of an isotropic electron plasma. To study the ionization
      process in the presence of the many-body interaction, a fully microscopic model
      is developed that combines a generalized version of the optical Bloch equations
      describing the optical excitation with a microscopic description of the many-body
      interactions. The numerical evaluation shows that the Coulomb interaction
      significantly modifies the distribution anisotropy already during the excitation
      process. Whereas a reduced anisotropy is still present after the pulse for low
      ionization degrees and pressures, it is completely absent for elevated gas
      densities. An ionization degree is predicted that is significantly enhanced by
      the many-body interactions. 

PMID- 24730953
TI  - Effect of magnetic field on the velocity autocorrelation and the caging of
      particles in two-dimensional Yukawa liquids.
AB  - We investigate the effect of an external magnetic field on the velocity
      autocorrelation function and the "caging" of the particles in a two-dimensional
      strongly coupled Yukawa liquid, via numerical simulations. The influence of the
      coupling strength on the position of the dominant peak in the frequency spectrum
      of the velocity autocorrelation function confirms the onset of a joint effect of
      the magnetic field and strong correlations at high coupling. Our molecular
      dynamics simulations quantify the decorrelation of the particles' surroundings:
      the magnetic field is found to increase significantly the caging time, which
      reaches values well beyond the time scale of plasma oscillations. The observation
      of the increased caging time is in accordance with findings that the magnetic
      field decreases diffusion in similar systems. 

PMID- 24730954
TI  - Investigation of fast-electron-induced Kalpha x rays in laser-produced blow-off
      plasma.
AB  - Refluxing of fast electrons generated by high-intensity, short-pulse lasers was
      investigated by measuring electron-induced Kalpha x rays from a buried tracer
      layer. Using planar foils of Au/Cu/CH, the 150-J, 0.7-ps TITAN short-pulse laser
      was focused on the gold foil to generate fast electrons and the 3-ns, 300-J long
      pulse beam irradiated on the CH side to create expanding plasma as a conducting
      medium. By delaying the short-pulse beam timing from the long pulse laser
      irradiation, the plasma size was varied to change electron refluxing in the
      target rear. The total yields and two-dimensional images of 8.05-keV Cu-Kalpha x
      ray were recorded with an x-ray spectrometer and two monochromatic crystal
      imagers. The measurements show that the integrated yields decrease by a factor of
      10 from refluxing to the nonrefluxing limit. Similar radial profiles of the
      Kalpha images in the rear were observed at all delays. Hybrid-particle-in-cell
      simulations using plasma profiles calculated by a radiation-hydrodynamic code
      HYDRA agree well with the measured Kalpha yields. The simulations suggest that
      conducting plasma with the size of ~300 MUm in the laser direction and ~600 MUm
      in the lateral direction at the density of 2 * 1020 1/cm3 is sufficiently large
      to prevent electrons from refluxing in the target. The parameters found in this
      study can be useful in designing experiments utilizing a Kalpha x-ray source in
      refluxing regime or a tracer layer in nonrefluxing regime. 

PMID- 24730955
TI  - Electron density compression and oscillating effects on laser energy absorption
      in overdense plasma targets.
AB  - An analytical model for energy absorption during the interaction of an
      ultrashort, ultraintense laser with an overdense plasma is proposed. Both the
      compression effect of the electron density profile and the oscillation of the
      electron plasma surface are self-consistently included, which exhibit significant
      influences on the laser energy absorption. Based on our model, the general
      scaling law of the compression effect depending on laser strength and initial
      density is derived, and the temporal variation of the laser absorption due to the
      boundary oscillating effect is presented. It is found that due to the oscillation
      of the electron plasma surface, the laser absorption rate will vibrate
      periodically at omega or 2omega frequency for the p-polarized and s-polarized
      laser, respectively. The effect of plasma collision on the laser absorption has
      also been investigated, which shows a considerable rise in absorption with
      increasing electron-ion collision frequency for both polarizations. 

PMID- 24730956
TI  - Deleterious effects of nonthermal electrons in shock ignition concept.
AB  - Shock ignition concept is a promising approach to inertial confinement fusion
      that may allow obtaining high fusion energy gains with the existing laser
      technology. However, the spike driving laser intensities in the range of 1-10
      PW/cm2 produces the energetic electrons that may have a significant effect on the
      target performance. The hybrid numerical simulations including a radiation
      hydrodynamic code coupled to a rapid Fokker-Planck module are used to asses the
      role of hot electrons in the shock generation and the target preheat in the time
      scale of 100 ps and spatial scale of 100 MUm. It is shown that depending on the
      electron energy distribution and the target density profile the hot electrons can
      either increase the shock amplitude or preheat the imploding shell. In
      particular, the exponential electron energy spectrum corresponding to the
      temperature of 30 keV in the present HiPER target design preheats the deuterium
      tritium shell and jeopardizes its compression. Ways of improving the target
      performance are suggested. 

PMID- 24730957
TI  - Charged-particle acceleration in braking plasma jets.
AB  - In this paper we describe the mechanism of the charged particle acceleration in
      space plasma systems. We consider the interaction of nonrelativistic particles
      with a sub-Alfvenic plasma jet originated from the magnetic reconnection. The
      sharp front with increased magnetic field amplitude forms in the jet leading
      edge. Propagation of the jet in the inhomogeneous background plasma results in
      front braking. We show that particles can interact with this front in a resonance
      manner. Synchronization of particle reflections from the front and the front
      braking provides the stable trapping of particles in the vicinity of the front.
      This trapping supports the effective particle acceleration along the front. The
      mechanism of acceleration is potentially important due to the prevalence of the
      magnetic reconnection in space and astrophysical plasmas. 

PMID- 24730958
TI  - Dynamics and stability of the Townsend discharge in nitrogen in narrow gaps.
AB  - This paper investigates the dynamics of the Townsend discharge in nitrogen in
      narrow gaps. To provide stability of discharge in a broad range of current, we
      apply a plane-parallel structure, one of the electrodes of which is made of a
      high-resistivity gallium arsenide. The results of experiments are analyzed in the
      framework of theory [Yu. P. Raizer et al., Tech. Phys. 51, 185 (2006)], which
      considers the dynamics of discharge in short nitrogen-filled gaps of similar
      structures. According to the theory, a key parameter of discharge dynamics is
      time theta that defines the rate of discharge response to perturbations. In our
      work, time theta is experimentally found by analyzing the noise spectrum of the
      discharge glow in the stable and spatially uniform state of the structure. This
      characteristic time depends linearly on the discharge gap width, which
      corroborates conclusions based on the standard model of Townsend discharge.
      However, its values are substantially shorter compared to those predicted by
      theory. The relationship between theta and experimentally observed critical
      current density for the oscillatory instability, jcr, is applied to find the
      discharge negative differential resistance for a set of parameters of the
      discharge gap. 

PMID- 24730959
TI  - Bounded dynamics in finite PT-symmetric magnetic metamaterials.
AB  - We examine the PT-symmetry-breaking transition for a magnetic metamaterial of a
      finite extent, modeled as an array of coupled split-ring resonators in the
      equivalent circuit model approximation. Small-size arrays are solved completely
      in closed form, while for arrays larger than N=5 results were computed
      numerically for several gain and loss spatial distributions. In all cases, it is
      found that the parameter stability window decreases rapidly with the size of the
      array, until at N=20 approximately it is not possible to support a stable PT
      symmetric phase. 

PMID- 24730960
TI  - Metric-signature topological transitions in dispersive metamaterials.
AB  - The metric signature topological transitions associated with the propagation of
      electromagnetic waves in a dispersive metamaterial with frequency-dependent and
      anisotropic dielectric and magnetic responses are examined in the present work.
      The components of the reciprocal-space metric tensor depend upon both the
      electric permittivity and magnetic permeability of the metamaterial, which are
      taken as Drude-like dispersive models. A thorough study of the frequency
      dependence of the metric tensor is presented which leads to the possibility of
      topological transitions of the isofrequency surface determining the wave dynamics
      inside the medium, to a diverging photonic density of states at some range of
      frequencies, and to the existence of large wave vectors' modes propagating
      through the metamaterial. 

PMID- 24730961
TI  - Compression by replication.
AB  - A recently introduced inference method based on system replication and an online
      message passing algorithm is employed to complete a previously suggested
      compression scheme based on a nonlinear perceptron. The algorithm is shown to
      approach the information theoretical bounds for compression as the number of
      replicated systems increases, offering superior performance compared to basic
      message passing algorithms. In addition, the suggested method does not require
      fine-tuning of parameters or other complementing heuristic techniques, such as
      the introduction of inertia terms, to improve convergence rates to nontrivial
      results. 

PMID- 24730962
TI  - Shrinkage of bubbles and drops in the lattice Boltzmann equation method for
      nonideal gases.
AB  - One characteristic of multiphase lattice Boltzmann equation (LBE) methods is that
      the interfacial region has a finite (i.e., noninfinitesimal) thickness known as a
      diffuse interface. In simulations of, e.g., bubble or drop dynamics, for problems
      involving nonideal gases, one frequently observes that the diffuse interface
      method produces a spontaneous, nonphysical shrinkage of the bubble or drop
      radius. In this paper, we analyze in detail a single-fluid two-phase model and
      use a LBE model for nonideal gases in order to explain this fundamental problem.
      For simplicity, we only investigate the static bubble or droplet problem. We find
      that the method indeed produces a density shift, bubble or droplet shrinkage, as
      well as a critical radius below which the bubble or droplet eventually vanishes.
      Assuming that the ratio between the interface thickness D and the initial bubble
      or droplet radius r0 is small, we analytically show the existence of this density
      shift, bubble or droplet radius shrinkage, and critical bubble or droplet
      survival radius. Numerical results confirm our analysis. We also consider
      droplets on a solid surface with different curvatures, contact angles, and
      initial droplet volumes. Numerical results show that the curvature, contact
      angle, and the initial droplet volume have an effect on this spontaneous
      shrinkage process, consistent with the survival criterion. 

PMID- 24730963
TI  - Vertex-based finite volume simulation of Liesegang patterns on structureless
      meshes.
AB  - A computational method is suggested for the simulation of Liesegang patterns in
      two dimensions on structureless meshes. The method is based on a model that
      incorporates dynamical equations for the nucleation and growth of solid particles
      of different sizes into reaction-diffusion equations. We find the model cannot be
      numerically solved with Galerkin-based finite element methods and cell-centered
      finite volume methods. Instead, the vertex-based finite volume method is used to
      correctly reproduce the Liesegang pattern on structureless meshes. The numerical
      solution is then compared with specially designed experiments on Liesegang
      patterns in various geometries, and it is shown to be in good agreement. 

PMID- 24730964
TI  - Calculation of space localized properties in correlated quantum Monte Carlo
      methods with reweighting: the nonlocality of statistical uncertainties.
AB  - We study the efficiency of quantum Monte Carlo (QMC) methods in computing space
      localized ground state properties (properties which do not depend on distant
      degrees of freedom) as a function of the system size N. We prove that for the
      commonly used correlated sampling with reweighting method, the statistical
      fluctuations sigma2(N) do not obey the locality property. sigma2(N) grow at least
      linearly with N and with a slope that is related to the fluctuations of the
      reweighting factors. We provide numerical illustrations of these tendencies in
      the form of QMC calculations on linear chains of hydrogen atoms. 

PMID- 24730965
TI  - Lattice Boltzmann method for linear oscillatory noncontinuum flows.
AB  - Oscillatory gas flows are commonly generated by micro- and nanoelectromechanical
      systems. Due to their small size and high operating frequencies, these devices
      often produce noncontinuum gas flows. Theoretical analysis of such flows requires
      solution of the unsteady Boltzmann equation, which can present a formidable
      challenge. In this article, we explore the applicability of the lattice Boltzmann
      (LB) method to such linear oscillatory noncontinuum flows; this method is derived
      from the linearized Boltzmann Bhatnagar-Gross-Krook (BGK) equation. We formulate
      four linearized LB models in the frequency domain, based on Gaussian-Hermite
      quadratures of different algebraic precision (AP). The performance of each model
      is assessed by comparison to high-accuracy numerical solutions to the linearized
      Boltzmann-BGK equation for oscillatory Couette flow. The numerical results
      demonstrate that high even-order LB models provide superior performance over the
      greatest noncontinuum range. Our results also highlight intrinsic deficiencies in
      the current LB framework, which is incapable of capturing noncontinuum behavior
      at high oscillation frequencies, regardless of quadrature AP and the Knudsen
      number. 

PMID- 24730966
TI  - Investigation of the kinetic model equations.
AB  - Currently the Boltzmann equation and its model equations are widely used in
      numerical predictions for dilute gas flows. The nonlinear integro-differential
      Boltzmann equation is the fundamental equation in the kinetic theory of dilute
      monatomic gases. By replacing the nonlinear fivefold collision integral term by a
      nonlinear relaxation term, its model equations such as the famous Bhatnagar-Gross
      Krook (BGK) equation are mathematically simple. Since the computational cost of
      solving model equations is much less than that of solving the full Boltzmann
      equation, the model equations are widely used in predicting rarefied flows,
      multiphase flows, chemical flows, and turbulent flows although their predictions
      are only qualitatively right for highly nonequilibrium flows in transitional
      regime. In this paper the differences between the Boltzmann equation and its
      model equations are investigated aiming at giving guidelines for the further
      development of kinetic models. By comparing the Boltzmann equation and its model
      equations using test cases with different nonequilibrium types, two factors (the
      information held by nonequilibrium moments and the different relaxation rates of
      high- and low-speed molecules) are found useful for adjusting the behaviors of
      modeled collision terms in kinetic regime. The usefulness of these two factors
      are confirmed by a generalized model collision term derived from a mathematical
      relation between the Boltzmann equation and BGK equation that is also derived in
      this paper. After the analysis of the difference between the Boltzmann equation
      and the BGK equation, an attempt at approximating the collision term is proposed.

PMID- 24730967
TI  - Collective translational and rotational Monte Carlo moves for attractive
      particles.
AB  - Virtual move Monte Carlo is a Monte Carlo (MC) cluster algorithm forming clusters
      via local energy gradients and approximating the collective kinetic or dynamic
      motion of attractive colloidal particles. We carefully describe, analyze, and
      test the algorithm. To formally validate the algorithm through highlighting its
      symmetries, we present alternative and compact ways of selecting and accepting
      clusters which illustrate the formal use of abstract concepts in the design of
      biased MC techniques: the superdetailed balance and the early rejection scheme. A
      brief and comprehensive summary of the algorithms is presented, which makes them
      accessible without needing to understand the details of the derivation. 

PMID- 24730968
TI  - Strong plastic deformation and softening of fast colliding nanoparticles.
AB  - Nanoparticles, with sizes ranging between 1 and ~102 nm, show dynamical
      properties distinctly different than those of bulk materials. Due to their large
      surface area to volume ratio, their properties often depend on length scales. We
      investigate the size and the collision velocity (vcoll) dependence of the
      coefficient of restitution (COR) for nanoparticles made of a face-centered cubic
      lattice of Lennard-Jones atoms via nonequilibrium molecular dynamics simulations.
      A sharp crossover between elastic collision and plastic collision occurs when
      vcoll=vY, where vY is the size-dependent yield velocity. For high-collision
      velocities the COR ~vcoll-alpha, alpha~1. This result is in agreement with recent
      small system simulations and with experiments and is distinct from the elasticity
      theory-based result for COR for inelastic collisions which behaves as vcoll
      alpha, with alpha=14. We find that the size-dependent critical vY approaches the
      theoretical constant value for macroscopic spheres as our particle sizes grow.
      Possible insights into the origins of alpha~1 and the size dependence of the
      yield velocity are suggested. The work also suggests that sufficiently fast
      moving nanoparticles traveling through vacuum could be sticky and hence could be
      of potential interest in many applications. 

PMID- 24730969
TI  - Free-energy-based lattice Boltzmann model for the simulation of multiphase flows
      with density contrast.
AB  - A free-energy-based phase-field lattice Boltzmann method is proposed in this work
      to simulate multiphase flows with density contrast. The present method is to
      improve the Zheng-Shu-Chew (ZSC) model [Zheng, Shu, and Chew, J. Comput. Phys.
      218, 353 (2006)] for correct consideration of density contrast in the momentum
      equation. The original ZSC model uses the particle distribution function in the
      lattice Boltzmann equation (LBE) for the mean density and momentum, which cannot
      properly consider the effect of local density variation in the momentum equation.
      To correctly consider it, the particle distribution function in the LBE must be
      for the local density and momentum. However, when the LBE of such distribution
      function is solved, it will encounter a severe numerical instability. To overcome
      this difficulty, a transformation, which is similar to the one used in the Lee
      Lin (LL) model [Lee and Lin, J. Comput. Phys. 206, 16 (2005)] is introduced in
      this work to change the particle distribution function for the local density and
      momentum into that for the mean density and momentum. As a result, the present
      model still uses the particle distribution function for the mean density and
      momentum, and in the meantime, considers the effect of local density variation in
      the LBE as a forcing term. Numerical examples demonstrate that both the present
      model and the LL model can correctly simulate multiphase flows with density
      contrast, and the present model has an obvious improvement over the ZSC model in
      terms of solution accuracy. In terms of computational time, the present model is
      less efficient than the ZSC model, but is much more efficient than the LL model. 

PMID- 24730970
TI  - Finite-difference lattice Boltzmann method with a block-structured adaptive-mesh
      refinement technique.
AB  - An adaptive-mesh-refinement (AMR) algorithm for the finite-difference lattice
      Boltzmann method (FDLBM) is presented in this study. The idea behind the proposed
      AMR is to remove the need for a tree-type data structure. Instead, pointer
      attributes are used to determine the neighbors of a certain block via appropriate
      adjustment of its children identifications. As a result, the memory and time
      required for tree traversal are completely eliminated, leaving us with an
      efficient algorithm that is easier to implement and use on parallel machines. To
      allow different mesh sizes at separate parts of the computational domain, the
      Eulerian formulation of the streaming process is invoked. As a result, there is
      no need for rescaling the distribution functions or using a temporal
      interpolation at the fine-coarse grid boundaries. The accuracy and efficiency of
      the proposed FDLBM AMR are extensively assessed by investigating a variety of
      vorticity-dominated flow fields, including Taylor-Green vortex flow, lid-driven
      cavity flow, thin shear layer flow, and the flow past a square cylinder. 

PMID- 24730971
TI  - Lattice Boltzmann simulations of multiple-droplet interaction dynamics.
AB  - A lattice Boltzmann (LB) formulation, which is consistent with the phase-field
      model for two-phase incompressible fluid, is proposed to model the interface
      dynamics of droplet impingement. The interparticle force is derived by comparing
      the macroscopic transport equations recovered from LB equations with the
      governing equations of the continuous phase-field model. The inconsistency
      between the existing LB implementations and the phase-field model in calculating
      the relaxation time at the phase interface is identified and an approximation is
      proposed to ensure the consistency with the phase-field model. It is also shown
      that the commonly used equilibrium velocity boundary for the binary fluid LB
      scheme does not conserve momentum at the wall boundary and a modified scheme is
      developed to ensure the momentum conservation at the boundary. In addition, a
      geometric formulation of the wetting boundary condition is proposed to replace
      the popular surface energy formulation and results show that the geometric
      approach enforces the prescribed contact angle better than the surface energy
      formulation in both static and dynamic wetting. The proposed LB formulation is
      applied to simulating droplet impingement dynamics in three dimensions and
      results are compared to those obtained with the continuous phase-field model, the
      LB simulations reported in the literature, and experimental data from the
      literature. The results show that the proposed LB simulation approach yields not
      only a significant speed improvement over the phase-field model in simulating
      droplet impingement dynamics on a submillimeter length scale, but also better
      accuracy than both the phase-field model and the previously reported LB
      techniques when compared to experimental data. Upon validation, the proposed LB
      modeling methodology is applied to the study of multiple-droplet impingement and
      interactions in three dimensions, which demonstrates its powerful capability of
      simulating extremely complex interface phenomena. 

PMID- 24730972
TI  - Extension of the continuum time-dependent Hartree-Fock method to proton states.
AB  - This paper deals with the solution of the spherically symmetric time-dependent
      Hartree-Fock approximation applied to nuclear giant monopole resonances in the
      small amplitude regime. The problem is spatially unbounded as the resonance state
      is in the continuum. The practical requirement to perform the calculation in a
      finite-sized spatial region yields an artificial boundary, which is not present
      physically. The question of how to ensure the boundary does not interfere with
      the internal solution, while keeping the overall calculation time low is studied.
      Here we propose an absorbing boundary condition scheme to handle the conflict.
      The derivation, via a Laplace transform method, and implementation is described.
      An inverse Laplace transform required by the absorbing boundaries is calculated
      using a method of nonlinear least squares. The accuracy and efficiency of the
      scheme is tested and results presented to support the case that they are an
      effective way of handling the artificial boundary. 

PMID- 24730973
TI  - Diffused bounce-back condition and refill algorithm for the lattice Boltzmann
      method.
AB  - A solid-fluid boundary condition for the lattice Boltzmann (LB) method, which
      retains the simplicity of the bounce-back method and leads to positive definite
      populations similar to the diffusive boundary condition, is presented. As a
      refill algorithm, it is proposed that quasi-equilibrium distributions be used to
      model distributions at fluid nodes uncovered due to solid movement. The method is
      tested for flow past an impulsively started cylinder and demonstrates
      considerable enhancement in the accuracy of the unsteady force calculation at
      moderate and high Reynolds numbers. Furthermore, via simulations, we show that
      momentum exchange procedure used in LB to compute forces is not Galilean
      invariant. A modified momentum exchange procedure is proposed to reduce the
      errors due to violation of Galilean invariance. 

PMID- 24730974
TI  - Hyaluronate-gold nanoparticle/tocilizumab complex for the treatment of rheumatoid
      arthritis.
AB  - Rheumatoid arthritis (RA) is a chronic inflammatory immune disease causing the
      inflammation of synovial membrane and the articular cartilage destruction. In
      this work, hyaluronate-gold nanoparticle/Tocilizumab (HA-AuNP/TCZ) complex was
      prepared for the treatment of RA. AuNP was used as a drug carrier with
      antiangiogenic effect. TCZ is a humanized monoclonal antibody against the
      interleukin-6 (IL-6) receptor and used as an immunosuppressive drug by
      interfering IL-6 in the pathogenesis of RA. HA is known to have cartilage
      protective and lubricant effects. HA was modified with cystamine via reductive
      amination, which was reduced with dithiothreitol (DTT) to prepare end-group
      thiolated HA (HA-SH). AuNP was chemically modified with HA-SH and physically
      modified with TCZ. The formation of HA-AuNP/TCZ complex was corroborated by UV
      vis spectroscopy, dynamic light scattering (DLS), and transmission electron
      microscopy (TEM). The therapeutic effect of HA-AuNP/TCZ complex on RA was
      confirmed in collagen-induced arthritis (CIA) model mice by ELISA, histological,
      and Western blot analyses. 

PMID- 24730976
TI  - A large kindred of pulmonary fibrosis associated with a novel ABCA3 gene variant.
AB  - BACKGROUND: Interstitial lung disease occurring in children is a condition
      characterized by high frequency of cases due to genetic aberrations of pulmonary
      surfactant homeostasis, that are also believed to be responsible of a fraction of
      familial pulmonary fibrosis. To our knowledge, ABCA3 gene was not previously
      reported as causative agent of fibrosis affecting both children and adults in the
      same kindred. METHODS: We investigated a large kindred in which two members, a
      girl whose interstitial lung disease was first recognized at age of 13, and an
      adult, showed a diffuse pulmonary fibrosis with marked differences in terms of
      morphology and imaging. An additional, asymptomatic family member was detected by
      genetic analysis. Surfactant abnormalities were investigated at biochemical, and
      genetic level, as well as by cell transfection experiments. RESULTS:
      Bronchoalveolar lavage fluid analysis of the patients revealed absence of
      surfactant protein C, whereas the gene sequence was normal. By contrast, sequence
      of the ABCA3 gene showed a novel homozygous G > A transition at nucleotide 2891,
      localized within exon 21, resulting in a glycine to aspartic acid change at codon
      964. Interestingly, the lung specimens from the girl displayed a morphologic
      usual interstitial pneumonitis-like pattern, whereas the specimens from one of
      the two adult patients showed rather a non specific interstitial pneumonitis-like
      pattern. CONCLUSIONS: We have detected a large kindred with a novel ABCA3
      mutation likely causing interstitial lung fibrosis affecting either young and
      adult family members. We suggest that ABCA3 gene should be considered in genetic
      testing in the occurrence of familial pulmonary fibrosis.

PMID- 24730975
TI  - Nucleic acid catalysis: metals, nucleobases, and other cofactors.

PMID- 24730977
TI  - The incidence and temporal patterning of insomnia: a second study.
AB  - Whether subjects with insomnia exhibit good sleep on some interval basis is
      unclear. Prior research suggests that patients with insomnia are highly variable
      with respect to night-to-night sleep continuity, that more than 40% of patients
      exhibit temporal patterning of good sleep, and that nearly 90% of patients
      exhibit better than average sleep following 1 to 3 nights of relatively poor
      sleep. The aim of the present study was to replicate and extend the above-noted
      findings utilizing: (i) a large sample studied over an extended time interval
      (ii) absolute standards for 'good' and 'poor' sleep; and (iii) a formal
      statistical methodology to assess temporal patterning and the association of time
      in bed with bout duration of poor or average sleep. Thirty-three subjects with
      insomnia and 33 good sleepers completed sleep diaries over the course of 110
      days. It was found that subjects with insomnia (compared to good sleepers) had
      more poor nights (e.g. about 39 versus 7% of the assessed nights), a higher
      probability of a having a poor night on any given occasion (60% greater
      probability than good sleepers) and more consecutive nights of poor sleep between
      good sleep nights (median bout duration of approximately three versus one night).
      Lastly, it was found that (as would be predicted by both the Spielman model and
      the two-process model) time in bed moderated bout duration in the insomnia group.
      That is, longer times in bed were associated with longer bouts of poor sleep.

PMID- 24730979
TI  - Direct synthesis of high-valent aryl-Cu(II) and aryl-Cu(III) compounds:
      mechanistic insight into arene C-H bond metalation.
AB  - Copper and its salts are abundant, inexpensive, and eco-friendly and have been
      used as the surrogates of noble metals to effect arene C-H bond activation and
      transformations. Despite of the recent significant progress of the study,
      syntheses of high-valent arylcopper(II-III) compounds are still very rare and
      mechanisms of copper(II)-catalyzed reactions remain elusive. With the use of
      azacalix[1]arene[3]pyridines as a platform, a number of arylcopper(II) compounds
      were synthesized efficiently from the reaction of Cu(ClO4)2 under ambient
      conditions. The resulting aryl-Cu(II) compounds, which contain an unprecedented
      (substituted) phenyl-Cu(II) sigma-bond, were stable under atmospheric conditions
      and can undergo facile oxidation reaction by free copper(II) ions or oxone to
      afford arylcopper(III) compounds in good yields. Both arylcopper(II) and
      arylcopper(III) compounds were characterized unambiguously by means of XRD, XPS,
      and NMR methods. Experimental evidence including reaction kinetics, LFER and KIE,
      and theoretical calculations indicated that the Cu(ClO4)2-mediated arene C-H bond
      activation proceeds plausibly through an electrophilic aromatic metalation
      pathway. The synthesis of high-valent arylcopper compounds and the reaction
      mechanism reported here highlight the diversity and richness of organocopper
      chemistry. 

PMID- 24730980
TI  - Commentary: ILAE definition of Epilepsy.

PMID- 24730981
TI  - Performance of different SNP panels for parentage testing in two East Asian
      cattle breeds.
AB  - The International Society for Animal Genetics (ISAG) proposed a panel of single
      nucleotide polymorphisms (SNPs) for parentage testing in cattle (a core panel of
      100 SNPs and an additional list of 100 SNPs). However, markers specific to East
      Asian taurine cattle breeds were not included, and no information is available as
      to whether the ISAG panel performs adequately for these breeds. We tested ISAG's
      core (100 SNP) and full (200 SNP) panels on two East Asian taurine breeds: the
      Korean Hanwoo and the Japanese Wagyu, the latter from the Australian herd. Even
      though the power of exclusion was high at 0.99 for both ISAG panels, the core
      panel performed poorly with 3.01% false-positive assignments in the Hanwoo
      population and 3.57% in the Wagyu. The full ISAG panel identified all sire
      offspring relations correctly in both populations with 0.02% of relations wrongly
      excluded in the Hanwoo population. Based on these results, we created and tested
      two population-specific marker panels: one for the Wagyu population, which showed
      no false-positive assignments with either 100 or 200 SNPs, and a second panel for
      the Hanwoo, which still had some false-positive assignments with 100 SNPs but no
      false positives using 200 SNPs. In conclusion, for parentage assignment in East
      Asian cattle breeds, only the full ISAG panel is adequate for parentage testing.
      If fewer markers should be used, it is advisable to use population-specific
      markers rather than the ISAG panel. 

PMID- 24730982
TI  - Phenolic characterisation of selected Salacia species using LC-ESI-MS/MS
      analysis.
AB  - Phenolic characterisation was carried out on the leaf of three Salacia species
      such as Salacia chinensis, Salacia fruticosa and Salacia oblonga using liquid
      chromatography coupled with quadrupole time of flight mass spectrometry equipped
      with electrospray ionisation interface. The estimation of total phenolics was
      carried out spectrophotometrically using Folin-Ciocalteu method. HPLC diode-array
      detection has been used for the preliminary identification of phenolic compounds,
      and liquid chromatography and mass spectrometry analyses were employed for their
      characterisation. The fragmentation patterns of the compounds during collision
      induced dissociation led to the structural elucidation of the separated
      compounds. 

PMID- 24730978
TI  - Diverse strategies targeting alpha7 homomeric and alpha6beta2* heteromeric
      nicotinic acetylcholine receptors for smoking cessation.
AB  - Preclinical studies suggest that a diversity of nicotinic acetylcholine receptors
      (nAChRs) with different sensitivities to nicotine may contribute to tobacco
      addiction. Using rodent intravenous nicotine self-administration as a preclinical
      model with good predictive validity for therapeutic efficacy for tobacco
      cessation, investigators have identified heteromeric alpha6beta2* and homomeric
      alpha7 nAChRs as promising novel therapeutic targets to promote smoking
      abstinence (*denotes possible assembly with other subunits). The data suggest
      that diverse strategies that target these subclasses of nAChRs, namely inhibition
      of alpha6beta2* nAChRs and stimulation of alpha7 nAChRs, will support tobacco
      cessation. alpha6beta2* nAChRs, members of the high-affinity family of beta2*
      nAChRs, function similarly to alpha4beta2* nAChRs, the primary target of the FDA
      approved drug varenicline, but have a much more selective neuroanatomical pattern
      of expression in catecholaminergic nuclei. Although activation of beta2* nAChRs
      facilitates nicotine self-administration, stimulation of alpha7 nAChRs appears to
      negatively modulate both nicotine reinforcement and beta2* nAChR function in the
      mesolimbic dopamine system. Although challenges and caveats must be considered in
      the development of therapeutics that target these nAChR subpopulations, an
      accumulation of data suggests that alpha7 nAChR agonists, partial agonists, or
      positive allosteric modulators and alpha6beta2* nAChR antagonists, partial
      agonists, or negative allosteric modulators may prove to be effective
      therapeutics for tobacco cessation. 

PMID- 24730983
TI  - Force-time course parameters and force fatigue model during an intermittent
      fatigue protocol in motorcycle race riders.
AB  - Fatigue in forearm muscles may be critical for motorcycle riders in relation to
      performance and forearm disorders. Force-time course parameters were examined to
      better characterize the reduction in the maximal force generating capacity (MVC)
      during an intermittent fatigue protocol (IFP) specifically designed for
      motorcycle riders. Also, a mathematical force fatigue model is proposed. Forty
      motorcyclists (aged 27.6 +/- 6.8 years) performed an IFP that simulated the
      braking gesture and posture of a rider. Fatigue was confirmed by a 40% decrement
      of the normalized MVC in comparison with basal value. Contraction time increased
      in comparison with basal condition (P <= 0.034). Relaxation kinetics presented
      two phases: (a) a pre-fatigue phase where half relaxation time (HRTraw ) and
      normalized (HRTnor ) decreased (P <= 0.013) while relaxation rate (RRraw )
      remained unchanged; and (b) a fatiguing phase where HRTraw , HRTnor increased and
      RRraw decreased (P <= 0.047). Normalized RRraw (RRnor ) declined progressively (P
      <= 0.016). The proposed nonlinear force fatigue model confirmed a satisfactory
      adjustment (R(2)  = 0.977 +/- 0.018). This mathematical expression derived three
      patterns of force fatigue: three-phase, exponential and linear, representing 70%,
      13%, and 17% of the participants, respectively. Overall, these results provided
      further support to force fatigue theoretical and applied proposals. 

PMID- 24730984
TI  - Structure-activity relationships for vitamin D3-based aromatic a-ring analogues
      as hedgehog pathway inhibitors.
AB  - A structure-activity relationship study for a series of vitamin D3-based (VD3)
      analogues that incorporate aromatic A-ring mimics with varying functionality has
      provided key insight into scaffold features that result in potent, selective
      Hedgehog (Hh) pathway inhibition. Three analogue subclasses containing (1) a
      single substitution at the ortho or para position of the aromatic A-ring, (2) a
      heteroaryl or biaryl moiety, or (3) multiple substituents on the aromatic A-ring
      were prepared and evaluated. Aromatic A-ring mimics incorporating either single
      or multiple hydrophilic moieties on a six-membered ring inhibited the Hh pathway
      in both Hh-dependent mouse embryonic fibroblasts and cultured cancer cells (IC50
      values 0.74-10 MUM). Preliminary studies were conducted to probe the cellular
      mechanisms through which VD3 and 5, the most active analogue, inhibit Hh
      signaling. These studies suggested that the anti-Hh activity of VD3 is primarily
      attributed to the vitamin D receptor, whereas 5 affects Hh inhibition through a
      separate mechanism. 

PMID- 24730985
TI  - The big case register.

PMID- 24730986
TI  - Gross anatomical study of the nerve supply of genitourinary structures in female
      mongrel hound dogs.
AB  - Anatomical variations in lumbosacral plexus or nerves to genitourinary structures
      in dogs are under described, despite their importance during surgery and
      potential contributions to neuromuscular syndromes. Gross dissection of 16 female
      mongrel hound dogs showed frequent variations in lumbosacral plexus
      classification, sympathetic ganglia, ventral rami input to nerves innervating
      genitourinary structures and pudendal nerve (PdN) branching. Lumbosacral plexus
      classification types were mixed, rather than pure, in 13 (82%) of dogs. The
      genitofemoral nerve (GFN) originated from ventral ramus of L4 in 67% of nerves,
      differing from the expected L3. Considerable variability was seen in ventral rami
      origins of pelvic (PN) and Pd nerves, with new findings of L7 contributions to
      PN, joining S1 and S2 input (23% of sides in 11 dogs) or S1-S3 input (5%), and to
      PdN, joining S1-S2, unilaterally, in one dog. L7 input was confirmed using
      retrograde dye tracing methods. The PN also received CG1 contributions,
      bilaterally, in one dog. The PdN branched unusually in two dogs. Lumbosacral
      sympathetic ganglia had variant intra-, inter- and multisegmental connectivity in
      6 (38%). Thus, the anatomy of mongrel dogs had higher variability than previously
      described for purebred dogs. Knowledge of this variant innervation during surgery
      could aid in the preservation of nerves and reduce risk of urinary and sexual
      dysfunctions. 

PMID- 24730987
TI  - Spatial factors influence arithmetic performance: the case of the minus sign.
AB  - Spatial features of mathematical equations may influence how people solve and
      interpret those equations. This study examined whether manipulations of spatial
      features affected how participants solved and interpreted equations involving the
      minus sign. Undergraduate participants (N = 91) solved multioperation arithmetic
      equations involving addition, subtraction, and multiplication (e.g., 25 - 3 + 2 *
      5 = __). We varied the spacing of the final three operands and the position of
      the first operator relative to the adjacent operands. Participants also generated
      a story problem to correspond with a given equation. We evaluated the procedures
      that participants used in solving the equations by analysing both their solutions
      and their written work. Both close spacing of the final three operands and
      position of the first operation sign influenced the procedures that participants
      used. Both of the spatial manipulations also influenced participants'
      interpretations of the conceptual structure of the equations, as revealed in the
      story problems that they generated. These results have implications for
      understanding how people process mathematical symbols and for mathematics
      education.

PMID- 24730988
TI  - [Clinical and epidemiological characteristics of patients hospitalized with
      severe influenza in the season 2012-2013].
AB  - AIM OF THE STUDY: To characterize the clinical and epidemiological features of
      patients hospitalized with moderate to severe influenza infection at the infec
      tious diseases department of a tertiary care hospital in the epidemic season 2012
      2013. MATERIAL AND METHODS: A prospective observational study of patients
      hospitalized with influenza infection in the season 2012-2013 was carried out at
      the Infectious Diseases Department, Na Bulovce Hospital in Prague. Influenza
      infection was diagnosed by real-time quantitative polymerase chain reaction (RT
      qPCR) in nasopharyngeal swab or tracheal aspirate specimens. Demographic,
      clinical, and laboratory data were recorded along with the disease course and
      outcome. RESULTS: One hundred and ninety-nine patients, 85 females and 114 males
      (age median 47, range 1-87 years), were hospitalized with confirmed influenza in
      the epidemic season 2012-2013. Only seven of them got the influenza vaccine.
      Altogether 136 patients were diagnosed with influenza type A (91 with H1N1pdm, 33
      with H3N2, and 12 with an unknown subtype), 66 patients with type B, and three
      patients with both types A and B. One hundred and eight patients (54%) had an
      underlying chronic disease, most often cardiovascular or pulmonary. The main
      symptoms of influenza were fever, cough, headache, myalgia, and arthralgia.
      Pneumonia was the most common complication: twenty-one patients suffered from
      primary viral pneumonia and 35 from bacterial pneumonia. Twenty-three patients
      (12%) needed intensive care. Six patients died and the leading cause of death was
      heart failure. CONCLUSION: During the epidemic influenza season 2012-2013, more
      patients were hospitalized than in the pandemic season 2009-2010. Also the
      proportions of complicated cases and case fatality ratios were fully comparable
      in both seasons. The fact that most patients were not vaccinated clearly supports
      the recommendation to vaccinate every year both the individuals at high risk of
      complications due to comorbidities and the healthy population.

PMID- 24730989
TI  - Influenza in seasons 2009-2013 in the Faculty Hospital Hradec Kralove, East
      Bohemia.
AB  - PURPOSE: The evaluation of four post-pandemic influenza seasons 2009-2013 in the
      Faculty hospital Hradec Kralove and comparison of used rapid antigen tests (RATs)
      with real time RT-PCR. MATERIAL AND METHODS: Between November 2009 and June 2013
      were examined 3845 samples from patients with respiratory tract infections by
      RATs (Influenza A/B 2 Panel Test (GECKO(r) Pharma, Germany), Rapid VIDITEST
      Influenza A+B Card (VIDIA(r), Czech Republic) and BinaxNOW Influenza A&B Test
      (ALERE(r), USA) or real time RT-PCR (RTR InfA/H1N1 Detection Set (Roche(r)),
      RealStar(r) Influenza S and T RT-PCR Kit 3.0 (Altona (r), Germany). RESULTS: A
      totally 1059 samples were examined simultaneously by RAT and real time RT-PCR.
      The overall sensitivity and specificity of RATs compared with real time RT-PCR
      were 32,2 % and 98,1 % for influenza A and 17,6 % and 99,4 % for influenza B.
      Higher sensitivity of RATs were in children (66,6 %) compared with adults (14,3 -
      40,0 %). In the first three post-pandemic seasons were continuously decrease of
      positive samples from 23,5 % in season 2009-2010 to 3,3% in season 2011-2012, but
      in season 2012-2013 were rapidly in-crease of positive results, to 31,5%, with
      high share of influenza -A/H1N1/2009 (79,6%). CONCLUSION: Our results shown
      insufficient sensitivity of all used RATs and necessity of having other
      confirmatory test, like RT-PCR. It was also shown unexplained increase of case
      and influenza severity in season 2012-2013.

PMID- 24730990
TI  - [Bacteria of the Burkholderia cepacia complex: epidemiology and diagnosis of
      infection in patients with cystic fibrosis].
AB  - Bacteria of the Burkholderia cepacia complex are the cause of severe lung
      infections primarily in patients with cystic fibrosis (CF). The risk of epidemic
      spread of the pathogen in the community of CF patients was the reason for
      implementing strict isolation measures and identifying the bacterium as early as
      possible. This review article features the taxonomy of the Burkholderia cepacia
      complex, possibilities for the laboratory diagnosis of all representatives of
      this complex, and epidemiological situation in the communities of CF patients in
      the Czech Republic and in the world. KEYWORDS: Burkholderia cepacia complex -
      cystic fibrosis - epidemic strain - pathogenesis of the infection.

PMID- 24730991
TI  - Epidemiological factors influencing the development of relapsing and severe
      Clostridium difficile infection.
AB  - INTRODUCTION: Clostridium difficile infection (CDI) is currently the most
      frequent cause of nosocomial infectious diarrhea in adults in the developed
      countries. The goal of the study was to evaluate risk factors for relapsing and
      severe CDI in a set of patients hospitalized at the Clinic of Infectious Diseases
      at the University Hospital Brno. MATERIALS AND METHODS: A retrospective analysis
      of epidemiological, clinical and laboratory data of 281 patients with proved CDI
      diagnosis hospitalized in the period from 1. 1. 2007 to 31. 12. 2010. RESULTS:
      Patient age over 65 is a risk for severe CDI (OR 2.95, p < 0.001) and extends
      hospitalization at the first episode of CDI by about 3.2 days on average.
      Patients with 2 or more comorbidities (p < 0.05) or with a history of recent
      hospitalization (p 0.001) are at risk for both relapsing CDI and severe CDI. The
      use of proton pump inhibitors may increase the number of relapses (OR 1.94, p <
      0.05). If the CDI symptoms appear within 7 days of taking antibiotics, there is a
      greater risk of relapse (OR 2.32, p < 0.05). If the symptoms occur after a longer
      period, a mild or moderate course of the disease can be expected (OR 0.31, p <
      0.05). CONCLUSIONS: To determine the risk level for development of relapsing or
      severe CDI, focus on risk factors from the patients medical history and their
      clinical and laboratory status is appropriate at the outset of CDI patients
      treatment. An early intensive monitoring of vital functions and administration of
      aggressive treatment can reduce complications, mortality and relapses of CDI.

PMID- 24730992
TI  - [Genotyping results, laboratory diagnosis, and epidemiology of the mumps virus
      circulating in the Czech Republic in 2012].
AB  - GOAL: To extend the present routine serological diagnosis of mumps with the
      methods of direct detection of the pathogen and subsequent genotyping of the
      isolated viruses in an attempt to obtain more detailed data on recent mumps
      viruses circulating in the Czech Republic. Sub-goals were to point out the
      particularities of the laboratory examination in the population with a high
      vaccine coverage and to evaluate the current epidemiological situation. MATERIAL
      AND METHODS: Altogether 47 buccal swabs from patients with suspected mumps were
      included in the study. Clinical specimens collected at the onset of clinical
      symptoms were obtained from five administrative regions of the Czech Republic
      from February 2012 to December 2012. Vero cell cultures were used for virus
      isolation and isolates were identified using real-time quantitative polymerase
      chain reaction (RT-qPCR). Genotyping was performed by the WHO Regional Reference
      Laboratory for Measles, Mumps, and Rubella (RRL MMR), Robert Koch Institute,
      Berlin. The EPIDAT system was used as a source of epidemiological data. RESULTS:
      From 47 buccal swabs, 20 mumps viruses were isolated on Vero cells and in seven
      other specimens, the presence of viral RNA without positive isolation was only
      detected by RT-qPCR. Nineteen isolates were referred for genotyping. The
      phylogenetic analysis of the SH gene classified them into genotype G, as four
      variants. In both 2011 and 2012, most cases occurred in vaccinated patients
      (80%), with 15-19-year-olds being the most affected age group. The leading
      complication was orchitis, followed by meningitis. More complications were
      reported in non-vaccinated individuals. CONCLUSIONS: The increased incidence of
      mumps cases in the Czech Republic in 2012 was due primarily to genotype G, the
      leading cause of mumps in most European countries since 2005. The presence of
      genotype G was first reported in the Czech Republic in 2006. In the context of
      the unfavourable epidemiological trend, molecular epidemiological studies
      including genotyping of recent mumps virus strains appear to be necessary. A
      detailed monitoring could be helpful in elucidating the pattern of virus
      circulation and in designing strategies to control emerging outbreaks. The
      vaccination efficacy in relation to the causative genotype and possible role of
      waning immunity in mumps outbreaks are the issues that need to be addressed.

PMID- 24730993
TI  - [Legionella infection--a neglected problem].
AB  - Pathogenic species of the Legionella genus can cause respiratory diseases ranging
      in severity from benign Pontiac fever to life-threatening Legionnaires disease
      often characterized by severe pneumonia, high fever, and multiple organ
      involvement. Predisposing underlying conditions, such as immunosuppression,
      chronic lung disease, and malignancies and other variables such as smoking and
      higher age constitute high-risk factors. Legionalla has been isolated from
      natural aquatic habitats (freshwater streams and lakes, water reservoirs, etc.),
      artificial sources, and also from humid soil. These pathogens are distributed
      worldwide. Besides water reservoirs (surface and underground water, fresh and
      salt water), they occur in a wide range of technical devices and systems - water
      distribution systems, showers, pools, spa systems, perlators, foggy makers,
      irrigation systems with sprinklers, cooling towers, etc. About 20% of detected
      Legionella infections in Europe have been associated with travel history. Travel
      associated cases present a particular difficulty in terms of identifying the
      source of infection and implementing remedial measures. KEYWORDS: Legionella
      pneumophila - Legionnaires disease - Pontiac fever - nosocomial infections.

PMID- 24730994
TI  - [Evaluation of prophylactic precautions after exposure to biological materials].
AB  - OBJECTIVES: Study of transmission rates of hepatitis B virus (HBV), hepatitis C
      virus (HCV), and human immunodeficiency virus (HIV) and effect of HBV vaccination
      after parenteral exposure to biological materials. PATIENTS AND METHODS: This was
      a retrospective study of 879 individuals (419 health care professionals and 460
      persons from the general population) after blood and body fluid exposure examined
      at the Clinic of Infectious Diseases in Ostrava from 1999 to 2013. HBsAg, anti
      HBs, anti-HBc, anti-HCV, anti-HIV, bilirubin, and ALT were tested in exposed
      patients and known sources at the baseline and, except anti-HBc, after 3, 6, and
      12 months. Susceptible persons were vaccinated against HBV and screened for anti
      HBs after 1-2 months. Antiretroviral prophylaxis was provided if reasonable.
      RESULTS: At the baseline, 42 exposed persons were HBV positive, six were HCV
      positive, and none was HIV positive. During the follow-up, no new HBsAg
      positivity was detected in exposed individuals, although 25 of 837 susceptible
      persons were exposed to HBsAg-positive sources. After vaccination, protective
      anti-HBs were detected in 707 (84.7%) of 837 susceptible persons and in 709
      (97.8%) of 725 persons with known post-vaccination response. Fifty-six of 873
      persons had been exposed to HCV-positive sources and HCV transmission was shown
      in three (two health care professionals) of them. No HIV transmission was
      observed, although 11 of 879 individuals had been exposed to HIV-positive
      sources, with antiretroviral prophylaxis provided to nine of them. CONCLUSIONS:
      Contemporary post-exposure prophylactic precautions in the Czech Republic can be
      considered as adequate for the prevention of HBV and HIV, but health care
      professionals in particular are at risk of HCV transmission.

PMID- 24730995
TI  - [Epidemiological investigation in five dental offices of the Clinic of Dentistry,
      Faculty of Medicine, Palacky University, Olomouc and of the Olomouc University
      Hospital].
AB  - The aim of this epidemiological investigation was to determine microbial
      contamination of surfaces, medical devices, and equipment in five outpatient
      dental offices of the Clinic of Dentistry, Faculty of Medicine, Palacky
      University, Olomouc and of the Olomouc University Hospital. The epidemiological
      investigation was carried out as a one-time detection of microbial contamination
      from selected at risk sites on the dental unit with chair and in its immediate
      surroundings that had been sampled before the staff and patients arrived in the
      morning. The rates of culture-negative results ranged from 6.0 % in the
      children's dental office to 17.3 % in the dental prosthetics office. No
      statistically significant difference in these rates was found between different
      types of dental offices. The most commonly identified microorganisms were
      coagulase-negative staphylococci and Bacillus sp. Pseudomonas aeruginosa often
      reported to be the cause of hospital infection was isolated from the spit-toon
      drain in most of the cases. No methicillin-resistant Staphylococcus aureus was
      cultured from the swabs. We believe that the microorganisms isolated from the at
      risk sites are indoor airborne pathogens initially present in aerosols and then
      deposited on surfaces during the time after working hours. KEYWORDS: dental
      office - bioaersol - contamination of surfaces - infectious agent.

PMID- 24730996
TI  - [Sequencing analysis of the antigens included in the four-component  vaccine
      against serogroup B meningococcus in Czech isolates of Neisseria meningitidis
      from 2007-2013].
AB  - OBJECTIVE: Study of the antigens included in the newly registered four-component
      vaccine against meningococcus B (MenB vaccine) produced by the reverse
      vaccinology method and assessment of the potential of the vaccine for use in the
      Czech Republic. MATERIAL AND METHODS: Czech isolates of Neisseria meningitidis
      were screened for four antigens: fHbp (factor H binding protein), NHBA (Neisseria
      heparin binding antigen), NadA (neisserial adhesin A), and PorA P1.4 outer
      membrane protein. A total of 304 N. meningitidis isolates from 2007-2013 were
      included in the study: 262 isolates from invasive meningococcal disease (IMD)
      (203 serogroup B isolates and 59 non-B isolates) and 42 isolates from healthy
      carriers. RESULTS: The gene encoding the fHbp peptide was detected in all study
      isolates from both IMD cases and healthy carriers. The two types of isolates
      differed in the distribution of fHbp variants. The fHbp1 variant prevailed in the
      IMD isolates (both B and non-B) while the fHbp2 variant was expressed more often
      in the carrier isolates. The presence of the nhba gene encoding the NHBA peptide
      was revealed in all study isolates from both IMD cases and healthy carriers. The
      serogroup B isolates from IMD cases differed from the non-B isolates from IMD
      cases and from the carrier isolates in the distribution of NHBA variants. The
      presence of the nadA gene encoding the NadA peptide was only found in 26.6% of
      serogroup B isolates from IMD cases in comparison to 40.7% of non-B isolates from
      IMD cases. As few as 4.8% of isolates from healthy carriers harboured the nadA
      gene. The PorA P1.4 protein included in the new MenB vaccine was only detected in
      two serogroup B isolates from IMD cases (of the total of 262 serogroup B and non
      B isolates from IMD cases) and in none of the isolates from healthy carriers.
      Isolates from both B and non-B IMD cases were positive most often for the
      combination of the antigens NHBA + fHbp1, followed by the NHBA antigen alone and
      then by the combination NHBA + fHbp1 + NadA-1+2/3. Isolates from healthy carriers
      showed a different antigen distribution pattern: the NHBA antigen alone was the
      most widespread, followed by the combination NHBA + fHbp1. CONCLUSIONS: The
      antigens included in the four-component MenB vaccine were revealed by sequencing
      in a large proportion of the Czech isolates of N. menin-gitidis from both IMD
      cases and healthy carriers. This four-component vaccine registered in Europe
      since January 2013 has proven suitable for use in the Czech Republic.

PMID- 24730997
TI  - Epidemiology of Cronobacter spp. isolates from patients admitted to the Olomouc
      University Hospital (Czech Republic).
AB  - The data on the incidence of Cronobacter spp. was collated from hospital records
      for the seven-year period 2005-2011. The majority of Cronobacter spp. isolates (n
      = 91) were from throat swabs (61), followed by urine (5), tracheal aspirates (5),
      bronchoalveolar lavage (4), cannulae (4), and sputum (3) samples. This is the
      first study which profiles the carriage of Cronobacter spp. according to patient
      age, based on seven years of clinical data from 2005-2011. It reveals a high
      recovery (63.7% of strains, n = 91) of the organism from children, 1-14 years in
      age. KEYWORDS: Cronobacter spp. - meningitis - nosocomial infection.

PMID- 24730998
TI  - Neuroprotective capabilities of TSA against cerebral ischemia/reperfusion injury
      via PI3K/Akt signaling pathway in rats.
AB  - BACKGROUND: Hundreds of previous studies demonstrated the cytoprotective effect
      of trichostatin-A (TSA), a kind of histone deacetylases inhibitors (HDACIs),
      against cerebral ischemia/reperfusion insult. Meanwhile, phosphatidylinositol-3
      kinase/Akt (PI3K/Akt) is a well-known, important signaling pathway that mediates
      neuroprotection. However, it should be remains unclear whether the
      neuroprotective capabilities of TSA against cerebral ischemia/reperfusion is
      mediated by activation of the PI3K/Akt signaling pathway. METHODS: Five groups
      rats (n = 12 each), with middle cerebral artery occlusion (MCAO) except sham
      group, were used to investigate the neuroprotective effect of certain
      concentration (0.05 mg/kg) of TSA, and whether the neuroprotective effect of TSA
      is associated with activation of the PI3K/Akt signaling pathway through using of
      wortmannin (0.25 mg/kg). RESULTS: TSA significantly increased the expression of p
      Akt protein, reduced infarct volume, and attenuated neurological deficit in rats
      with transient MCAO, wortmannin weakened such effect of TSA dramatically.
      CONCLUSIONS: TSA could significantly decrease the neurological deficit scores and
      reduce the cerebral infarct volume during cerebral ischemia/reperfusion injury,
      which was achieved partly by activation of the PI3K/Akt signaling pathway via
      upgrading of p-Akt protein.

PMID- 24730999
TI  - Neurolight -astonishing advances in brain imaging.
AB  - In recent years, significant advances in basic neuroanatomical studies have taken
      place. Moreover, such classical, clinically-oriented human brain imaging methods
      such as MRI, PET and DTI have been applied to small laboratory animals allowing
      improvement in current experimental neuroscience. Contemporary structural
      neurobiology also uses various technologies based on fluorescent proteins. One of
      these is optogenetics, which integrates physics, genetics and bioengineering to
      enable temporal precise control of electrical activity of specific neurons.
      Another important challenge in the field is the accurate imaging of complicated
      neural networks. To address this problem, three-dimensional reconstruction
      techniques and retrograde labeling with modified viruses has been developed.
      However, a revolutionary step was the invention of the "Brainbow" system,
      utilizing gene constructs including the sequences of fluorescent proteins and the
      usage of Cre recombinase to create dozens of colour combinations, enabling
      visualization of neurons and their connections in extremely high resolution.
      Furthermore, the newly- introduced CLARITY method should make it possible to
      visualize three-dimensionally the structure of translucent brain tissue using the
      hydrogel polymeric network. This original technique is a big advance in
      neuroscience creating novel viewpoints completely different than standard glass
      slide immunostaining. 

PMID- 24731000
TI  - Pathophysiology and diagnosis of Guillain-Barre syndrome - challenges and needs.
AB  - Guillain-Barre syndrome (GBS) is an autoimmune polyneuropathy which presents with
      acute onset and rapid progression of flaccid, hyporeflexi quadriparesis. Both
      sensory and autonomic nerve involvement is seen. GBS has various subtypes that
      vary in their pathophysiology. The pathogenesis involves an immune response
      triggered by a preceding event which may be an infection, immunisation or
      surgical procedure. Clinical diagnosis has been largely the primary diagnosing
      criterion for GBS along with electrodiagnosis, which has several pitfalls and is
      supported by ancillary testing of cerebrospinal fluid (CSF) analysis and Nerve
      Conduction Studies. Measurement of anti-ganglioside antibodies is also an
      effective tool in its diagnosis. Further understanding of pathophysiology and
      better diagnostic methods are required for better management of GBS. 

PMID- 24731001
TI  - High-performance organic complementary inverters using monolayer graphene
      electrodes.
AB  - Chemical vapor deposition-grown graphene has been an attractive electrode
      material for organic electronic devices, such as organic field-effect transistors
      (OFETs), because it is highly conductive and provides good oxidation and thermal
      stability properties. However, it still remains a challenge to demonstrate
      organic complementary circuits using graphene electrodes because of the
      relatively poor performance of n-type OFETs. Here, we report the development of
      high-performance organic complementary inverters using graphene as source/drain
      electrodes and N, N'-ditridecyl-3,4,9,10-perylenetetracarboxylic diimide (PTCDI
      C13) and pentacene as n- and p-type organic semiconductors, respectively.
      Graphene electrodes were n-doped via the formation of NH2-terminated self
      assembled monolayers that lowered the work function and the electron injection
      barrier between the graphene and PTCDI-C13. Thermal annealing improved the
      molecular packing among PTCDI-C13 groups on the graphene surface, thereby
      increasing the crystallinity and grain size. The thermally annealed PTCDI-C13
      OFETs prepared using n-doped graphene electrodes exhibited a good field-effect
      mobility of up to 0.43 cm2/(V s), which was comparable to the values obtained
      from other p-type pentacene OFETs. By integrating p- and n-type OFETs, we
      successfully fabricated organic complementary inverters that exhibited highly
      symmetric operation with an excellent voltage gain of up to 124 and good noise
      margin.

PMID- 24731002
TI  - An unanticipated role for survivin in organ transplant damage.
AB  - Ischemia/reperfusion (I/R) injury is a major determinant of graft survival in
      kidney transplantation. Survivin, an inhibitor of apoptosis that participates in
      the control of mitosis and cell cycle progression, has been implicated in renal
      protection and repair after I/R injury; however, no study has been performed in
      the transplant setting. We investigated the role of survivin in modulating
      posttransplant I/R injury in syngeneic and allogeneic kidney grafts, and studied
      whether protection from I/R injury impacted on the recipient immune system, on
      chronic allograft nephropathy and rejection. We used genetically engineered mice
      with survivin haploinsufficiency and WT mice in which survivin over-expression
      was induced by gene-delivery. Survivin haploinsufficiency in syngeneic grafts was
      associated with exuberant I/R tissue injury, which triggered inflammation
      eventually resulting in graft loss. Conversely, survivin over-expression in the
      grafts minimized I/R injury and dysfunction in syngeneic grafts and in a
      clinically relevant fully MHC-mismatched allogeneic combination. In the latter,
      survivin over-expression translated into limited anti-donor adaptive immune
      response and less long-term allograft injury with protection from renal
      parenchymal damage. Our data support survivin over-expression in the graft as a
      novel target for protocols aimed at limiting tissue damage at the time of
      transplant ultimately modulating the recipient immune system. 

PMID- 24731003
TI  - A comprehensive review of milk fouling on heated surfaces.
AB  - Heat exchanger performance degrades rapidly during operation due to formation of
      deposits on heat transfer surfaces which ultimately reduces service life of the
      equipment. Due to scaling, product deteriorates which causes lack of proper
      heating. Chemistry of milk scaling is qualitatively understood and the
      mathematical models for fouling at low temperatures have been produced but the
      behavior of systems at ultra high temperature processing has to be studied
      further to understand in depth. In diversified field, the effect of whey protein
      fouling along with pressure drop in heat exchangers were conducted by many
      researchers. Adding additives, treatment of heat exchanger surfaces and changing
      of heat exchanger configurations are notable areas of investigation in milk
      fouling. The present review highlighted information about previous work on
      fouling, influencing parameters of fouling and its mitigation approach and ends
      up with recommendations for retardation of milk fouling and necessary measures to
      perform the task. 

PMID- 24731004
TI  - Thermocapillary flow in glass tubes coated with photoresponsive layers.
AB  - Thermocapillary flow has proven to be a good alternative to induce and control
      the motion of drops and bubbles in microchannels. Temperature gradients are
      usually established by implanting metallic heaters adjacent to the channel or by
      including a layer of photosensitive material capable of absorbing radiative
      energy. In this work we show that single drops can be pumped through capillaries
      coated with a photoresponsive composite (PDMS + carbon nanopowder) and irradiated
      with a light source via an optical fiber. Maximum droplet speeds achieved with
      this approach were found to be ~300 MUm/s, and maximum displacements, around 120%
      of the droplet length. The heat generation capacity of the coatings was proven
      having either a complete coating over the capillary surface or a periodic array
      of pearls of the photoresponsive material along the capillary produced by the so
      called Rayleigh-Plateau instability. The effect of the photoresponsive layer
      thickness and contact angle hysteresis of the solid-liquid interface were found
      to be important parameters in the photoinduced thermocapillary effect.
      Furthermore, a linear relationship between the optical intensity I(o) and droplet
      velocity v was found for a wide range of the former, allowing us to analyze the
      results and estimate response times for heat transfer using heat conduction
      theory.

PMID- 24731005
TI  - Selective effects of arm proximal and distal muscles fatigue on force
      coordination in manipulation tasks.
AB  - Effects of muscle fatigue on force coordination and task performance of various
      manipulation tasks are explored. Grip force (GF; normal force component acting at
      the digits-object contact area) and load force (LF; tangential component that
      lifts and holds objects) were recorded prior to and after fatiguing the distal
      (DAM; i.e., GF producing) and proximal arm muscles (PAM; LF producing). Results
      reveal a deterioration of GF scaling (i.e., averaged GF-LF ratio), GF-LF coupling
      (their correlation), and task performance (ability to exert a prescribed LF
      pattern) associated with DAM, but not PAM fatigue. Deteriorated force
      coordination clearly increases the likelihood of dropping an object; however, the
      observed selective effects of DAM and PAM fatigue represent a novel finding
      deserving of further research.

PMID- 24731007
TI  - Effectiveness of preventive and corrective surgical intervention on hip disorders
      in severe cerebral palsy: a systematic review.
AB  - PURPOSE: This review presents an overview of the effectiveness of preventive and
      corrective surgical interventions to treat hip displacement in patients with
      severe cerebral palsy (CP). METHOD: A systematic literature search was applied to
      identify studies concerning surgical procedures in hip(sub)luxations in severe CP
      (GMFCS IV and V). A qualitative analysis and a best evidence synthesis were
      performed for soft tissue surgery and osteotomies. RESULTS: The literature search
      identified 15 studies, all of which were observational. Five studies involved
      soft tissue surgery and 10 involved osteotomies. Only one study involving soft
      tissue surgery was of sufficient quality. Nine of the 10 studies involving
      osteotomies were of sufficient quality, including a total of 189 patients. The
      mean MP (migration percentage) at follow-up ranged from 6 to 29%. No relationship
      could be established between the effect of the surgical procedure and the
      patients' age or the duration of follow-up. The percentage of patients reporting
      pain decreased from 81% preoperatively to 5% at follow-up. Twenty-five percent
      had complications such as osteoarthritis, ulcers or fractures. CONCLUSIONS: There
      is insufficient evidence for the effectiveness of soft tissue surgery to
      stabilize the hip, due to insufficient quality of the retrospective observational
      studies. This review shows indicative findings (provided by consistent,
      statistically significant findings on outcome and/or process measures in at least
      two Observational Studies with sufficient quality) for an effect of bony surgery
      in stabilizing the hip. Timing of the procedure remains an issue. Multicenter
      trials could shed further light on this complicated subject.

PMID- 24731006
TI  - Role of autophagy in high linear energy transfer radiation-induced cytotoxicity
      to tumor cells.
AB  - Heavy-ion radiotherapy has a potential advantage over conventional radiotherapy
      due to improved dose distribution and a higher biological effectiveness in cancer
      therapy. However, there is a little information currently available on the
      cellular and molecular basis for heavy-ion irradiation-induced cell death.
      Autophagy, as a novel important target to improve anticancer therapy, has
      recently attracted considerable attention. In this study, the effect of autophagy
      induced by high linear energy transfer (LET) carbon ions was examined in various
      tumor cell lines. To our knowledge, our study is the first to reveal that high
      LET carbon ions could induce autophagy in various tumor cells effectively, and
      the autophagic level in the irradiated cells increased in a dose- and LET
      dependent manner. The ability of carbon ions to inhibit the activation of the
      PI3K/Akt pathway rose with increasing their LET. Moreover, modulation of
      autophagy in tumor cells could modify their sensitivity to high-LET radiation,
      and inhibiting autophagy accelerated apoptotic cell death, resulting in an
      increase in radiosensitivity. Our data imply that targeting autophagy might
      enhance the effectiveness of heavy-ion radiotherapy. 

PMID- 24731008
TI  - Hepatic glucose sensing is impaired, but can be normalized, in people with
      impaired fasting glucose.
AB  - OBJECTIVE: Abnormal endogenous glucose production (EGP) is a characteristic
      feature in people with impaired fasting glucose (IFG). We sought to determine
      whether impaired hepatic glucose sensing contributes to abnormal EGP in IFG and
      whether it could be experimentally restored. METHODS: Glucose production (rate of
      appearance; Ra) and flux (glucose cycling) were assessed during a hyperglycemic
      euinsulinemic somatostatin clamp with an infusion of [6,6-(2)H2-]glucose and [2
      (2)H]glucose before and after enhanced hepatic glucokinase activity via an
      infusion of low-dose fructose in people with IFG and normal glucose tolerance
      (NGT). RESULTS: During euglycemia, neither endogenous glucose production [(6,6
      (2)H2)-glucose Ra; P = 0.53] or total glucose output (TGO; [2-(2)H]-glucose Ra; P
      = .12) was different between groups, but glucose cycling ([2-(2)H]glucose Ra to
      [6,6-(2)H2-]glucose Ra; a surrogate measure of hepatic glucokinase activity in
      the postabsorptive state) was lower in IFG than NGT (P = .04). Hyperglycemia
      suppressed EGP more in NGT than IFG (P < .01 for absolute or relative
      suppression, NGT vs IFG), whereas TGO decreased similarly in both groups (P =
      .77). The addition of fructose completely suppressed EGP in IFG (P < .01) and
      tended to do the same to TGO (P = .01; no such changes in NGT, P = .39-.55).
      Glucose cycling (which reflects glucose-6-phosphatase activity during glucose
      infusion) was similar in IFG and NGT (P = .51) during hyperglycemia and was
      unchanged and comparable between groups with the addition of fructose (P = .24).
      CONCLUSIONS: In summary, glucose sensing is impaired in IFG but can be
      experimentally restored with low-dose fructose. Glucokinase activation may prove
      to be a novel strategy for the prevention of diabetes in this high-risk group.

PMID- 24731009
TI  - A control engineering model of calcium regulation.
AB  - CONTEXT: A control engineering perspective provides a framework for representing
      important mechanistic details of the calcium (Ca) regulatory system efficiently.
      The resulting model facilitates the testing of hypotheses about mechanisms
      underlying the emergence of known Ca-related pathologies. OBJECTIVE: The
      objective of this work is to develop a comprehensive computational model that
      will enable quantitative understanding of plasma Ca regulation under normal and
      pathological conditions. DESIGN: Ca regulation is represented as an engineering
      control system where physiological subprocesses are mapped onto corresponding
      block components (sensor, controller, actuator, and process), and underlying
      mechanisms are represented by differential equations. The resulting model is
      validated with clinical observations of induced hypo- or hypercalcemia in healthy
      subjects, and its applicability is demonstrated by comparing model predictions of
      Ca-related pathologies to corresponding clinical data. RESULTS: Our model
      accurately predicts clinical responses to induced hypo- and hypercalcemia in
      healthy subjects within a framework that facilitates the representation of Ca
      related pathologies in terms of control system component defects. The model also
      enables a deeper understanding of the emergence of pathologies and the testing of
      hypotheses about related features of Ca regulation-for example, why primary
      hyperparathyroidism and hypoparathyroidism arise from "controller defects."
      CONCLUSIONS: The control engineering framework provides an efficient means of
      organizing the subprocesses constituting Ca regulation, thereby facilitating a
      fundamental understanding of this complex process. The resulting validated
      model's predictions are consistent with clinically observed short- and long-term
      dynamic characteristics of the Ca regulatory system in both healthy and diseased
      patients. The model also enables simulation of currently infeasible clinical
      tests and generates predictions of physiological variables that are currently not
      measurable.

PMID- 24731010
TI  - Serum 25-hydroxyvitamin D and incidence of diabetes in elderly people: the
      PRO.V.A. study.
AB  - CONTEXT: Increasing research has shown that low levels of serum 25-hydroxyvitamin
      (25OHD) predict the onset of diabetes, but no research is available on this issue
      in elderly people. OBJECTIVE: Our objective was to examine whether low serum
      levels of 25OHD are associated with a higher risk of incident type 2 diabetes
      over a lengthy follow-up in a representative group of elderly people. DESIGN AND
      SETTING: This was a population-based cohort study as part of the Progetto Veneto
      Anziani (Pro.V.A.) Study over a follow-up of 4.4 years in the general community.
      PARTICIPANTS: PARTICIPANTS included 2227 participants (1728 with follow-up visits
      and 499 died during the follow-up) over 65 years of age without diabetes at
      baseline, of 2352 initially included. MAIN OUTCOME MEASURE: The main outcome
      measure was incident diabetes. RESULTS: There were no baseline differences in
      known factors for the onset of diabetes (body mass index, waist circumference,
      total cholesterol, renal function, and hemoglobin A1c levels) between the groups
      with different serum 25OHD levels (<= 25, 25-50, 50-75, and >= 75 nmol/L). Over a
      4.4-year follow-up, 291 individuals developed diabetes, with an incidence of 28
      events per 1000 person-years. No significant difference in the incidence of
      diabetes emerged between the baseline 25OHD groups. Cox's regression analysis,
      adjusted for potential confounders, revealed no relationship between low vitamin
      D levels and incident diabetes during the follow-up (hazard ratio [HR] = 1.05,
      95% confidence interval [CI] = 0.76-1.45, P = .77; HR = 1.44, 95% CI = 0.95-1.98,
      P = .12; and HR = 1.37, 95% CI = 0.87-2.16, P = .17 for those with 25OHD <=25, 25
      50, and 50-75 nmol/L, respectively). CONCLUSION: Baseline serum concentrations of
      25OHD were not associated with the incidence of diabetes in community-dwelling
      elderly people over a follow-up of 4.4 years.

PMID- 24731011
TI  - Serum estradiol associates with blood hemoglobin in elderly men: the MrOS Sweden
      study.
AB  - CONTEXT: Blood hemoglobin (Hb) declines with age in healthy elderly men, in whom
      decreasing T has been regarded as part of normal aging. However, the association
      between Hb and serum estradiol is incompletely known. OBJECTIVE: To determine
      whether estradiol is associated with anemia/Hb and established determinants of Hb
      in elderly men without prostate cancer. DESIGN, SETTING, AND PARTICIPANTS: The
      MrOS (Osteoporotic Fractures in Men) is a population-based study (n = 918; median
      age, 75.3 y; range, 70-81 y). MAIN OUTCOME MEASURES: We evaluated total estradiol
      in relation to Hb and adjusted for potential confounders (ie, age, body mass
      index [BMI], erythropoietin [EPO], total T, cystatin C, and iron and B-vitamin
      status). RESULTS: Estradiol correlated negatively with age (r = -0.14; P < .001).
      Hb correlated (age adjusted) positively with estradiol (r = 0.21; P < .001) and T
      (r = 0.10; P < .01). Independent predictors for Hb in multivariate analyses were
      estradiol, EPO, BMI, transferrin saturation, cystatin C, and free T4, but not T.
      After exclusion of subjects with Hb <130 g/L and/or T < 8 nmol/L (n = 99), the
      correlation between Hb and T was no longer significant, whereas the associations
      between Hb and estradiol remained. After adjusting for age, BMI, and EPO, men
      with lower estradiol levels were more likely to have Hb in the lowest quartile of
      values (odds ratio per SD decrease in estradiol = 1.61 [95% confidence interval,
      1.34-1.93]). Anemic subjects (Hb < 130 g/L) had lower mean estradiol than
      nonanemic subjects (67.4 vs 79.4 pmol/L; P < .001). CONCLUSIONS: Estradiol
      correlated positively and independently with Hb. Decreased estradiol might partly
      explain the age-related Hb decline observed in healthy elderly men.

PMID- 24731012
TI  - Primary hyperparathyroidism in young people. When should we perform genetic
      testing for multiple endocrine neoplasia 1 (MEN-1)?
AB  - CONTEXT: Multiple endocrine neoplasia (MEN-1) is a rare, autosomal dominant
      inherited disorder. Primary hyperparathyroidism (pHPT) is the most frequent and
      usually the earliest expression of MEN-1, with typical age of onset at 20-25
      years. Early detection of the disease and correct treatment are therefore of
      great importance. CASE PRESENTATION: A 31-year-old woman with osteogenesis
      imperfecta was incidentally found also to have hypercalcemia and elevated PTH
      (pHPT). Exploratory neck surgery showed multiglandular parathyroid affection; she
      turned out to have MEN-1, but she was diagnosed 7 years after her debut of pHPT.
      OBJECTIVE AND METHODS: The aim was to search literature on indications for
      performing mutational analysis in young patients with pHPT and no family history
      of MEN-1. PubMed was searched for English language articles, and words used were:
      MEN1 OR MEN-1 OR MEN type 1 OR multiple endocrine neoplasia 1 OR multiple
      endocrine neoplasia type 1 AND Mutational analysis OR genetic testing OR testing
      OR Hyperparathyroidism, primary [majr]. A total of 625 abstracts were reviewed.
      RESULTS AND DISCUSSION: Whether to perform screening of patients with pHPT under
      the age of 30, 35, or 40 years is controversial. According to international
      guidelines from 2001, genetic testing is indicated only in patients with pHPT
      below the age of 30 years. However, in updated guidelines from 2012, it is
      suggested to perform genetic testing in patients with pHPT below the age of 30
      years, but also at any age in patients presenting with multigland parathyroid
      disease. CONCLUSIONS: The reviewed literature and the presented case illustrate
      the importance of this change in international guidelines, but they also raise
      concern for a potential underdiagnosing of patients before year 2012.

PMID- 24731013
TI  - High frequency of X chromosome abnormalities in women with short stature and
      elevated liver enzymes.
AB  - CONTEXT: Paucisymptomatic forms of Turner's syndrome (TS), in which short stature
      is the predominant clinical abnormality, remain underdiagnosed. Abnormal liver
      tests are extremely frequent in adult TS patients reflecting various types of
      hepatic lesions. OBJECTIVE: The objective of the study was to investigate whether
      unexplained elevated liver enzymes in women with short stature could reveal X
      chromosome abnormalities of undiagnosed TS. DESIGN AND PARTICIPANTS: Thirty-one
      consecutive short stature women displaying elevated liver enzymes and no previous
      diagnosis of TS were compared with 31 age-matched controls in a prospective
      study. Liver biopsy was performed in 26 patients. MAIN OUTCOME MEASURES:
      Systematic karyotype analysis and fluorescence in situ hybridization. RESULTS: X
      chromosome abnormalities were found in 27 patients and one control (87.0% vs
      3.2%, P < .0001), including a 45,X/46,XX mosaicism in 24 patients and
      isochromosome of the long arm in three. Liver histological analysis showed
      architectural changes in 17 patients with nodular regenerative hyperplasia in 12.
      Biliary lesions were present in 13 patients and liver steatosis in 20.
      CONCLUSIONS: X chromosome abnormalities indicative of cryptic TS are extremely
      frequent in short-stature women with unexplained elevated liver enzymes. In short
      stature women, abnormal liver tests should lead to systematic karyotype analysis.

PMID- 24731014
TI  - Codon Arg15 mutations of the AP2S1 gene: common occurrence in familial
      hypocalciuric hypercalcemia cases negative for calcium-sensing receptor (CASR)
      mutations.
AB  - CONTEXT: Familial hypocalciuric hypercalcemia (FHH) is an autosomal dominant
      disorder with three known subtypes: FHH1, FHH2, and FHH3. About 65% of FHH cases
      are FHH1, caused by inactivating mutations of the calcium-sensing receptor (CASR)
      gene. FHH3 was recently found to be caused by codon Arg15 (p.R15) mutations in
      the adaptor-related protein complex 2, sigma-2 subunit that interacts with the
      CaSR and is encoded by the AP2S1 gene. OBJECTIVE: The objective of the study was
      to assess the prevalence of AP2S1 mutations, and describe the phenotype of FHH3,
      in an independent cohort of FHH subjects lacking CASR mutations. PATIENTS AND
      METHODS: Thirty-nine patients presenting with some combination of hypercalcemia,
      hypermagnesemia, nonsuppressed serum PTH levels, and reduced urinary calcium
      excretion were studied. Exon 2 of the AP2S1 gene was PCR amplified from patient
      genomic DNA and Sanger sequenced. The presence of p.R15 mutations was confirmed
      by restriction enzyme analysis. RESULTS: Five of the 39 subjects had AP2S1 p.R15
      mutations, a frequency of 13%. The three recurrent mutations reported previously
      were all found in our cohort (p.R15C in two, p.R15L in two, and p.R15H in one
      subject). The FHH3 phenotype did not differ materially from that of FHH1 due to
      CASR mutations. CONCLUSIONS: The results affirm that a significant number of
      patients suspected of having FHH but proven negative for CASR mutation have AP2S1
      p.R15 mutations. Screening for AP2S1 p.R15 mutations in such cases should be
      considered, given the clinical benefits (avoiding unnecessary parathyroidectomy)
      that have already been demonstrated for CASR screening in FHH1.

PMID- 24731015
TI  - The short and long term effects of exercise training in non-cystic fibrosis
      bronchiectasis--a randomised controlled trial.
AB  - BACKGROUND: Exercise training is recommended for non-cystic fibrosis (CF)
      bronchiectasis, but the long-term effects are unclear. This randomised controlled
      trial aimed to determine the effects of exercise training and review of airway
      clearance therapy (ACT) on exercise capacity, health related quality of life
      (HRQOL) and the incidence of acute exacerbations in people with non-CF
      bronchiectasis. METHODS: Participants were randomly allocated to 8 weeks of
      supervised exercise training and review of ACT, or control. Primary outcomes of
      exercise capacity and HRQOL (Chronic respiratory disease questionnaire) and
      secondary outcomes of cough-related QOL (Leicester cough questionnaire) and
      psychological symptoms (Hospital anxiety and depression scale) were measured at
      baseline, following completion of the intervention period and at 6 and 12 months
      follow up. Secondary outcomes of the exacerbation rate and time to first
      exacerbation were analysed over 12 months. RESULTS: Eighty-five participants
      (mean FEV1 74% predicted; median Modified Medical Research Council Dyspnoea grade
      of 1 (IQR [1-3]) were included. Exercise training increased the incremental
      shuttle walk distance (mean difference to control 62 m, 95% CI 24 to 101 m) and
      the 6-minute walking distance (mean difference to control 41 m, 95% CI 19 to 63
      m), but these improvements were not sustained at 6 or 12 months. Exercise
      training reduced dyspnoea (p = 0.009) and fatigue (p = 0.01) but did not impact
      on cough-related QOL or mood. Exercise training reduced the frequency of acute
      exacerbations (median 1[IQR 1-3]) compared to the control group (2[1-3]) over 12
      months follow up (p = 0.012), with a longer time to first exacerbation with
      exercise training of 8 months (95% CI 7 to 9 months) compared to the control
      group (6 months [95% CI 5 to 7 months], p = 0.047). CONCLUSIONS: Exercise
      training in bronchiectasis is associated with short term improvement in exercise
      capacity, dyspnoea and fatigue and fewer exacerbations over 12 months. TRIAL
      REGISTRY: ClinicalTrials.gov (NCT00885521).

PMID- 24731016
TI  - High-resolution melt analysis does not reveal mutagenic risk in sexed sperm and
      in vitro-derived bovine embryos.
AB  - The objectives of the present work were to verify whether simultaneous exposure
      to Hoechst 33342 and UV irradiation during sorting by flow cytometry may induce
      gene point mutations in bovine sperm and to assess whether the dye incorporated
      in the sperm may imply a mutagenic effect during the embryonic development. To
      this aim, high-resolution melt analysis (HRMA) was used to discriminate
      variations of single nucleotides in sexed vs. non-sexed control samples. Three
      batches of sorted and non-sorted commercial semen of seven bulls (42 samples)
      were subjected to HRMA. A set of 139 genes located on all the chromosomes was
      selected, and 407 regions of the genome covering a total of 83 907 bases were
      analyzed. Thereafter, sperm of one sexed and one non-sexed batch of each bull was
      used in in vitro fertilization, and the derived embryos were analyzed (n = 560).
      One hundred and thirty-three regions of the bovine genome, located in 40 genes,
      were screened for a total coverage of 23 397 bases. The comparison between the
      frequencies of variations, with respect to the sequences deposited, observed in
      the sexed and non-sexed sperm (843 vs. 770) and embryos (246 vs. 212) showed no
      significant differences (P > 0.05), as measured by chi-square tests. It can be
      concluded that staining with Hoechst 33342 and exposure to UV during sorting does
      not lead to significant changes in the frequencies of variants in the commercial
      sexed semen and in embryos produced in vitro with the same treated sperm.

PMID- 24731017
TI  - Obstructive sleep apnea is associated with increased arterial stiffness in severe
      obesity.
AB  - Obstructive sleep apnea is associated with obesity and metabolic syndrome,
      leading to greater cardiovascular risk. Severely obese patients with obstructive
      sleep apnea may still be at risk of adverse health outcomes, even without
      previous cardiovascular disease. Pulse wave analysis non-invasively measures
      peripheral pulse waveforms and derives measures of haemodynamic status, including
      arterial stiffness, augmentation pressure and subendocardial viability ratio. We
      hypothesized that the presence of obstructive sleep apnea in severe obesity, even
      in the absence of an antecedent history of cardiovascular disease, would affect
      measurements derived from pulse wave analysis. Seventy-two severely obese adult
      subjects [obstructive sleep apnea 47 (body mass index 42 +/- 7 kg m(-2) ),
      without obstructive sleep apnea (non-OSA) 25 (body mass index 40 +/- 5 kg m(-2)
      )] were characterised using anthropometric, respiratory and cardio-metabolic
      parameters. Groups were similar in age, body mass index and gender. More subjects
      with obstructive sleep apnea had metabolic syndrome [obstructive sleep apnea 60%,
      without obstructive sleep apnea (non-OSA) 12%]. Those with obstructive sleep
      apnea had greater arterial stiffness, augmentation pressure and decreased
      subendocardial viability ratio (all P < 0.001), with significantly higher
      systolic (P = 0.003), diastolic (P = 0.04) and mean arterial pressures (P =
      0.004) than patients without obstructive sleep apnea (non-OSA). Arterial
      stiffness correlated with mean arterial blood pressure (P = 0.003) and
      obstructive sleep apnea severity (apnea-hypopnea index; P < 0.001). apnea
      hypopnea index significantly predicted arterial stiffness in multiple regression
      analysis, but components of the metabolic syndrome did not. Thus, patients with
      obstructive sleep apnea with severe obesity have increased arterial stiffness
      that may potentially influence cardiovascular risk independently of metabolic
      abnormalities. The presence of obstructive sleep apnea in severe obesity
      identifies a group at high cardiovascular risk; clinicians should ensure that
      risk factors are managed appropriately in this group whether or not treatment of
      obstructive sleep apnea is offered or accepted by patients. 

PMID- 24731018
TI  - Proton-coupled electron transfer in molecular electrocatalysis: theoretical
      methods and design principles.
AB  - Molecular electrocatalysts play an essential role in a wide range of energy
      conversion processes. The objective of electrocatalyst design is to maximize the
      turnover frequency and minimize the overpotential for the overall catalytic
      cycle. Typically, the catalytic cycle is dominated by key proton-coupled electron
      transfer (PCET) processes comprised of sequential or concerted electron and
      proton transfer steps. Theoretical methods have been developed to investigate the
      mechanisms, thermodynamics, and kinetics of PCET processes in electrocatalytic
      cycles. Electronic structure methods can be used to calculate the reduction
      potentials and pKa's and to generate thermodynamic schemes, free energy reaction
      pathways, and Pourbaix diagrams, which indicate the most stable species under
      certain conditions. These types of calculations have assisted in identifying the
      thermodynamically favorable mechanisms under specified experimental conditions,
      such as acid strength and overpotential. Such calculations have also revealed
      linear correlations among the thermodynamic properties, which can be used to
      predict the impact of modifying the ligands, substituents, or metal centers. The
      thermodynamic properties can be tuned with electron-withdrawing or electron
      donating substituents. Ligand modification can exploit the role of noninnocent
      ligands. For example, ligand protonation typically decreases the overpotential.
      Calculations of rate constants for electron and proton transfer, as well as
      concerted PCET, have assisted in identifying the kinetically favorable mechanisms
      under specified conditions. The concerted PCET mechanism is thought to lower the
      overpotential required for catalysis by avoiding high-energy intermediates. Rate
      constant calculations have revealed that the concerted mechanism involving
      intramolecular proton transfer will be favored by designing more flexible ligands
      that facilitate the proton donor-acceptor motion while also maintaining a
      sufficiently short equilibrium proton donor-acceptor distance. Overall,
      theoretical methods have assisted in the interpretation of experimental data and
      the design of more effective molecular electrocatalysts. 

PMID- 24731021
TI  - Introduction to the clinical definition of epilepsy by the ILAE president.

PMID- 24731020
TI  - Second peak in the distribution of age at onset of ulcerative colitis in relation
      to smoking cessation.
AB  - BACKGROUND AND AIM: The prevalence of ulcerative colitis (UC) is increasing
      steadily in Japan. In Western countries, a bimodal distribution, with UC onset
      peaks in youth and middle age, is observed, and smoking cessation is reported as
      a risk factor for UC. However, there are few reports on a bimodal distribution of
      onset age among Japanese patients. Therefore, the distribution of onset age and
      factors related to late onset (i.e. onset at 50 years old or later) were
      investigated in UC patients in Japan. METHODS: A questionnaire survey of UC
      patients was conducted to investigate the distribution of the age of onset and
      factors that may be related to UC onset in a Japanese university hospital.
      RESULTS: Among 465 UC patients, 343 patients responded. In the distribution of
      onset age, a large peak was seen in patients aged 10-20s, and small peaks were
      seen at age 40-44 years and then in 50-60s. In addition, the onset age was older
      in the UC patients diagnosed in 2001 or later than in those diagnosed in 2000 or
      earlier. Late onset was more common among the UC patients diagnosed in 2001 or
      later (vs 2000 or earlier: interaction odds ratio = 4.98, 95% CI: 2.21-11.25, P <
      0.01) and among former smokers (vs never-smokers: interaction odds ratio = 2.93,
      95% CI: 1.40-6.14, P < 0.01) on multivariate analysis. CONCLUSIONS: Similar to UC
      patients in Western countries, a bimodal distribution of onset age was also
      observed in Japanese UC patients, and smoking cessation may partly contribute to
      the increase in late-onset UC patients in recent years in Japan.

PMID- 24731019
TI  - Carboxylate-assisted C(sp3)-H activation in olefin metathesis-relevant ruthenium
      complexes.
AB  - The mechanism of C-H activation at metathesis-relevant ruthenium(II) benzylidene
      complexes was studied both experimentally and computationally. Synthesis of a
      ruthenium dicarboxylate at a low temperature allowed for direct observation of
      the C-H activation step, independent of the initial anionic ligand-exchange
      reactions. A first-order reaction supports an intramolecular concerted metalation
      deprotonation mechanism with DeltaG(?)(298K) = 22.2 +/- 0.1 kcal.mol(-1) for the
      parent N-adamantyl-N'-mesityl complex. An experimentally determined DeltaS(?) = 
      5.2 +/- 2.6 eu supports a highly ordered transition state for carboxylate
      assisted C(sp(3))-H activation. Experimental results, including measurement of a
      large primary kinetic isotope effect (k(H)/k(D) = 8.1 +/- 1.7), agree closely
      with a computed six-membered carboxylate-assisted C-H activation mechanism where
      the deprotonating carboxylate adopts a pseudo-apical geometry, displacing the
      aryl ether chelate. The rate of cyclometalation was found to be influenced by
      both the electronics of the assisting carboxylate and the ruthenium ligand
      environment.

PMID- 24731022
TI  - Surface modification with dopamine and heparin/poly-L-lysine nanoparticles
      provides a favorable release behavior for the healing of vascular stent lesions.
AB  - Surface biofunctional modification of coronary artery stents to prevent
      thrombosis and restenosis formation, as well as accelerate endothelialization,
      has become a new hot spot. However, bioactive coatings on implants are not yet
      sufficiently developed for long-term activity, as they quickly lose efficiency in
      vivo and finally fail. On the basis of a novel time-ordered concept of
      biofunctionality for vascular stents, heparin/poly l-lysine nanoparticle (NP) was
      developed and immobilized on a polydopamine-coated titanium surface, with the aim
      of regulating and maintaining the intravascular biological response within the
      normal range after biomaterial implantation. An in vitro dynamic release model
      was established to mimic the blood flow condition in vivo with three phases: (1)
      An early phase (1-7 days) with release of predominantly anticoagulant and anti
      inflammatory substances and to a minor degree antiproliferative effects against
      smooth muscle cells (SMCs); (2) this is followed by a phase (7-14 days) of
      supported endothelial cell (ECs) proliferation and suppressed SMC proliferation
      with persisting high antithrombogenicity and anti-inflammatory properties of the
      surface. (3) Finally, a stable stage (14-28 days) with adequate biomolecules on
      the surface that maintain hemocompatibility and anti inflammation as well as
      inhibit SMCs proliferation and promote ECs growth. In vivo animal tests further
      confirmed that the NP-modified surface provides a favorable release behavior to
      apply a stage-adjusted remedy. We suggested that these observations provide
      important guidance and potential means for reasonable and suitable platform
      construction on a stent surface.

PMID- 24731023
TI  - Remote ischemic preconditioning delays fatigue development during handgrip
      exercise.
AB  - Ischemic preconditioning (IPC) of one or two limbs improves performance of
      exercise that recruits the same limb(s). However, it is unclear whether IPC
      application to another limb than that in exercise is also effective and which
      mechanisms are involved. We investigated the effect of remote IPC (RIPC) on
      muscle fatigue, time to task failure, forearm hemodynamics, and deoxygenation
      during handgrip exercise. Thirteen men underwent RIPC in the lower limbs or a
      control intervention (CON), in random order, and then performed a constant load
      rhythmic handgrip protocol until task failure. Rates of contraction and
      relaxation (DeltaForce/DeltaTime) were used as indices of fatigue. Brachial
      artery blood flow and conductance, besides forearm microvascular deoxygenation,
      were assessed during exercise. RIPC attenuated the slowing of contraction and
      relaxation throughout exercise (P < 0.05 vs CON) and increased time to task
      failure by 11.2% (95% confidence interval: 0.7-21.7%, P <0.05 vs CON). There was
      no significant difference in blood flow, conductance, and deoxygenation between
      conditions throughout exercise (P > 0.05). In conclusion, RIPC applied to the
      lower limbs delayed the development of fatigue during handgrip exercise,
      prolonged time to task failure, but was not accompanied by changes in forearm
      hemodynamics and deoxygenation. 

PMID- 24731024
TI  - 'Will walk for groceries': Acceptability of financial health incentives among
      Canadian cardiac rehabilitation patients.
AB  - Financial health incentives, such as paying people to exercise, remain
      controversial despite widespread implementation. This focus group study explored
      the acceptability of incentives among a sample of Canadian cardiac rehabilitation
      (CR) patients (n = 15). Focus groups were conducted between March and April 2013
      until further sampling ceased to produce new analytical concepts. A thematic
      analysis approach was adopted in analysing the data. Three broad themes emerged
      from the focus groups. First, ethical concerns were prominent. Half of
      participants disagreed with the incentive approach believing that it was unfair,
      unnecessary or a waste of limited resources. Second, ethical concerns were
      mitigated in considering a range of incentive features including type, size and
      source. Specifically, privately sponsored (not government funded) health
      promoting voucher-based incentives (e.g., grocery or gym vouchers) were perceived
      to be highly acceptable. Third, if designed like this, then financial incentives
      were considered potentially effective in motivating behaviour change and in
      reducing economic barriers to exercise participation. Overall, the majority of
      participants welcomed incentives if ethical concerns were addressed through
      thoughtful incentive programme design. The results of this focus group study will
      inform the design of a financial health incentive feasibility RCT to promote post
      CR programme exercise compliance in this population.

PMID- 24731025
TI  - Population screening for Wilson's disease.
AB  - Wilson's disease is an autosomal recessive disorder of copper transport caused by
      mutations in the gene encoding an ATPase, ATP7B. Early detection of Wilson's
      disease is critical because effective medical treatments such as chelating agents
      and zinc salts are available, which can prevent lifelong neurological
      disabilities and/or cirrhosis. It is unfortunate that most patients are brought
      to our attention after they have developed serious complications such as brain
      damage or cirrhosis, despite the availability of effective treatments. The
      diagnosis is usually made through copper measurement in the liver tissue,
      followed by confirmation with genetic testing of the ATP7B gene. Currently, there
      are no effective biomarkers or methods suitable for newborn screening for
      Wilson's disease. Ceruloplasmin has been tested for pediatric and newborn
      screening with limited outcome. Recently, liquid chromatography-multiple reaction
      monitoring-mass spectrometry (LC-MRM-MS) has emerged as a robust technology that
      may enable multiplex quantification of signature proteotypic peptides with low
      abundance. The application of this technology may help facilitate the research on
      Wilson's disease for protein expression, biomarker study, diagnosis, and,
      hopefully, screening. 

PMID- 24731026
TI  - Outcomes of men with an elevated prostate-specific antigen (PSA) level as their
      sole preoperative intermediate- or high-risk feature.
AB  - OBJECTIVE: To investigate the post-prostatectomy and long-term outcomes of men
      presenting with an elevated pretreatment prostate-specific antigen (PSA) level
      (>10 ng/mL), but otherwise low-risk features (biopsy Gleason score <=6 and
      clinical stage <=T2a). PATIENTS AND METHODS: PSA-incongruent intermediate-risk
      (PII) cases were defined as those patients with preoperative PSA >10 and <=20
      ng/mL but otherwise low-risk features, and PSA-incongruent high-risk (PIH) cases
      were defined as men with PSA >20 ng/mL but otherwise low-risk features. Our
      institutional radical prostatectomy database (1992-2012) was queried and the
      results were stratified into D'Amico low-, intermediate- and high risk, PSA
      incongruent intermediate-risk and PSA-incongruent high-risk cases. Prostate
      cancer (PCa) features and outcomes were evaluated using appropriate comparative
      tests. Multivariable analyses were adjusted for age, race and year of surgery.
      RESULTS: Of the total cohort of 17 608 men, 1132 (6.4%) had PII-risk disease and
      183 (1.0%) had PIH-risk disease. Compared with the low-risk group, the odds of
      upgrading at radical prostatectomy (RP) were 2.20 (95% CI 1.93-2.52; P < 0.001)
      for the PII group and 3.58 (95% CI 2.64-4.85; P < 0.001) for the PIH group, the
      odds of extraprostatic disease at RP were 2.35 (95% CI 2.05-2.68; P < 0.001) for
      the PII group and 6.68 (95% CI 4.89-9.15; P < 0.001) for the PIH group, and the
      odds of positive surgical margins were 1.97 (95% CI 1.67-2.33; P < 0.001) for the
      PII group and 3.54 (95% CI 2.50-4.95, P < 0.001) for the PIH group. Compared with
      low-risk disease, PII-risk disease was associated with a 2.85-, 2.99- and 3.32
      fold greater risk of biochemical recurrence (BCR), metastasis and PCa-specific
      mortality, respectively, and PIH-risk disease was associated with a 5.32-, 6.14-
      and 7.07-fold greater risk of BCR, metastasis and PCa-specific mortality,
      respectively (P <= 0.001 for all comparisons). For the PII group, the higher
      risks of positive surgical margins, upgrading, upstaging and BCR were dependent
      on PSA density (PSAD): men in the PII group who had a PSAD <0.15 ng/mL/g were not
      at higher risk compared with those in the low-risk group. Men in the PII group
      with a PSAD >=0.15 ng/mL/g and men in the PIH group were more likely to have an
      anterior component of the dominant tumour (59 and 64%, respectively) compared
      with those in the low- (35%) and intermediate-risk group (39%) and those in the
      PII-risk group with PSAD <0.15 ng/mL/g (29%). CONCLUSIONS: Men with PSA >20 ng/mL
      or men with PSA >10 and <=20 ng/mL with a PSAD >=0.15 ng/mL/g, but otherwise low
      risk PCa, are at greater risk of adverse pathological and oncological outcomes
      and may be inappropriate candidates for active surveillance. These men are at
      greater risk of having anterior tumours that are undersampled at biopsy, so if
      treatment is deferred, ancillary testing such as anterior zone sampling or
      magnetic resonance imaging should be strongly encouraged. Men with elevated PSA
      levels >10 and <=20 ng/mL but low PSAD have outcomes similar to those in the low
      risk group, and consideration of surveillance is appropriate in these cases.

PMID- 24731028
TI  - Old age is no time to be doing time.

PMID- 24731027
TI  - Soluble interleukin-6 receptor levels and risk of dementia: one more signpost on
      a long road ahead.

PMID- 24731029
TI  - Both sides now.

PMID- 24731030
TI  - Effectiveness of an evidence-based multidisciplinary falls prevention program in
      reducing falls in high-risk older people.

PMID- 24731031
TI  - Bringing palliative care into geriatrics in a Chinese culture society--results of
      a collaborative model between palliative medicine and geriatrics unit in Hong
      Kong.

PMID- 24731032
TI  - Lower limb and abdominal compression in the management of orthostatic hypotension
      -not supported by the evidence.

PMID- 24731033
TI  - Avoiding emergency department admissions using telephonic consultations between
      general practitioners and hospital geriatricians.

PMID- 24731034
TI  - Arterial compliance plateaus in healthy aging women--in time for preventive
      treatment.

PMID- 24731035
TI  - Mycosis fungoides in elderly adults--a diagnostic challenge.

PMID- 24731036
TI  - Pantoprazole sodium-induced hyponatremia in a frail elderly adult.

PMID- 24731037
TI  - The effect of short, unplanned hospitalizations on older adult functional status.

PMID- 24731038
TI  - Statins and the trajectory of cognitive decline.

PMID- 24731039
TI  - Response to Buslovich and colleagues.

PMID- 24731040
TI  - Drug Burden Index for international assessment of the functional burden of
      medications in older people.

PMID- 24731041
TI  - Response to Sarah Hilmer and colleagues.

PMID- 24731042
TI  - Martin S. Bergmann's legacy: a tribute.

PMID- 24731043
TI  - The twilight of the training analysis system.
AB  - This paper briefly reviews challenges to psychoanalysis at this time, including
      those derived from both external, societal origins and internal psychoanalytic
      problems. It focuses attention on serious conflicts around psychoanalytic
      education, and refers to the training analysis system as a central problem
      determining fundamental constraints on present-day psychoanalytic education.
      These constraints are examined in some detail, and the general advantages and
      disadvantages of the training analysis system are outlined. The effects of all
      these dynamics on the administrative organization of the American Psychoanalytic
      Association are explored, and a proposal for a fundamental reorganization of our
      educational system to resolve the correspondent problems is outlined. 

PMID- 24731044
TI  - On psychoanalytic supervision as signature pedagogy.
AB  - What is signature pedagogy in psychoanalytic education? This paper examines that
      question, considering why psychoanalytic supervision best deserves that
      designation. In focusing on supervision as signature pedagogy, I accentuate its
      role in building psychoanalytic habits of mind, habits of hand, and habits of
      heart, and transforming theory and self-knowledge into practical product. Other
      facets of supervision as signature pedagogy addressed in this paper include its
      features of engagement, uncertainty, formation, and pervasiveness, as well as
      levels of surface, deep, and implicit structure. Epistemological, ontological,
      and axiological in nature, psychoanalytic supervision engages trainees in
      learning to do, think, and value what psychoanalytic practitioners in the field
      do, think, and value: It is, most fundamentally, professional preparation for
      competent, "good work." In this paper, effort is made to shine a light on and
      celebrate the pivotal role of supervision in "making" or developing budding
      psychoanalysts and psychoanalytic psychotherapists. Now over a century old,
      psychoanalytic supervision remains unparalleled in (1) connecting and integrating
      conceptualization and practice, (2) transforming psychoanalytic theory and self
      knowledge into an informed analyzing instrument, and (3) teaching, transmitting,
      and perpetuating the traditions, practice, and culture of psychoanalytic
      treatment. 

PMID- 24731045
TI  - Teaching professional ethics in psychoanalytic institutes: engaging the inner
      ethicist.
AB  - Teaching professional ethics in psychoanalytic institutes begins with two
      assumptions: (1) Students learn not only a code of ethics, they learn to develop
      their inner ethicist. (2) Institutes do not "train" students to become versed in
      a professional discipline, institutes educate, so students acquire a complex
      range of knowledge, developing intellectually and emotionally. Studying
      professional ethics begins with questions concerning freedom, free will, and
      responsibility, allowing students to contemplate emotionally charged topics:
      power politics, collegial relationships, organizational malfeasance, and boundary
      violations. Another area of concern involves the ability to observe and manage
      countertransference. Another related theme is trust: trust in supervisors,
      training analysts, instructors, and one's own ability to process
      countertransference. Processing countertransference is a necessary ethical
      obligation. Instructors need to be aware of the emotional stresses involved in
      studying professional ethics, particularly in discussions of sexual boundary
      violations. Students developing an ethical stance can enhance creativity in
      psychoanalytic work. 

PMID- 24731046
TI  - The dynamic interplay of mourning and forgiveness in the early development of the
      self and psychic structure.
AB  - Mourning has received considerable attention in the psychoanalytic literature.
      Beginning with Freud's 1917 investigation, the central role of mourning in
      psychical development via identification has been articulated and subsequently
      elaborated upon by various authors (e.g., Klein, 1940; Schafer, 2005).
      Forgiveness, on the other hand, has until recently received considerably less
      attention, perhaps because of the strong religious and moral connotations often
      associated with it (Lansky, 2009a). Contemporary writers exploring the
      psychoanalytic implications of mourning and forgiveness, however, have suggested
      the importance of both in normal psychical development. The purpose of this paper
      is to propose an integrated model of mourning and forgiveness and explore its
      potential role in nascent infant development. 

PMID- 24731047
TI  - The roots of evil: a psychoanalytic inquiry.
AB  - Of all the great dualities of human experience, "good and evil" have been the
      most instrumental in shaping the beliefs, rituals, and laws of Homo sapiens. The
      polarization of our nature into "good and bad" and anthropomorphic
      externalizations of these impulsions have been with us for millennia, providing
      inspiration for magical rites, representational forms, and the cornucopia of
      dramas, narratives, and artworks to which they give expression. Furthermore,
      whereas all religions advocate for good, the particular narratives of evil
      underlying the traditions of Western culture come to us from the Bible. However,
      good and especially evil are theological and moral, not psychological,
      constructs. With Freud's death instinct, and later Fromm's necrophilous
      character, the darker shadow of human nature became definitively secularized.
      After an introduction and historical/developmental overview of select theorists,
      this paper adopts a strictly psychoanalytic frame of reference in the exploration
      of what renders some human beings capable of doing inhuman things. Looking at
      behaviors manifesting through the psychodynamics of character structure and
      severe personality disorders, the breakdown of empathy and defacement of the
      "other" in the creation of an enemy is discussed. In conclusion two clinical
      portraits are offered, illustrating how primitive emotions and defenses, superego
      pathology, and latent schizoid, narcissistic, and projective mechanisms provide
      fuel and rationalization for malignant aggressive, duplicitous, and sadistic
      behaviors. 

PMID- 24731048
TI  - Winnicott and Arendt: bridging potential and political spaces.
AB  - In this article, the author seeks to bridge analytic theory, which is used as an
      interpretive framework to understand patients' psychic lives, and political
      philosophy, which accounts for individuals living a life in common as citizens.
      Specifically, I address how we can understand the relation between the
      psychosocial space of a parent(s) and child interaction, which becomes part of
      the child's psychic life, and the political space between and within citizens.
      The underlying claim is that there is a correlation between political space and
      the space between parent and child. I use an emended version of Donald
      Winnicott's concept of potential space and political philosopher Hannah Arendt's
      notion of the space of appearances to suggest connections between the consulting
      room and political space. 

PMID- 24731051
TI  - Effects of DNA repair gene polymorphisms on DNA damage in human lymphocytes
      induced by a vinyl chloride metabolite in vitro.
AB  - BACKGROUND: Epidemiologic studies suggest that variability in DNA damage from
      vinyl chloride monomer (VCM) may be partially mediated by genetic polymorphisms
      in DNA repair. This study aimed to corroborate these observations with controlled
      experiments in vitro using cell lines from individuals with differing DNA repair
      genotypes to determine damage following VCM metabolite exposure. METHODS: Matched
      pairs of lymphoblast cell lines (homozygous wild-type versus homozygous variant
      for either XRCC1 399 or XPD 751 polymorphism) were exposed to chloroacetaldehyde
      and analyzed by the cytokinesis-block micronucleus assay. RESULTS: All cell lines
      demonstrated a dose-response of increasing micronuclei with increasing exposure,
      but for both XRCC1 and XPD, the polymorphic cells peaked at higher micronucleus
      frequencies and declined at a slower rate to baseline than the wild-type cells.
      CONCLUSION: This supports the findings that XRCC1 and XPD polymorphisms may
      result in deficient DNA repair of VCM-induced genetic damage.

PMID- 24731050
TI  - Characterization of ASKP1240, a fully human antibody targeting human CD40 with
      potent immunosuppressive effects.
AB  - Blocking the CD40-CD154 interaction is reported to be effective for
      transplantation management and autoimmune disease models in rodents and nonhuman
      primates. However, clinical trials with anti-CD154 mAbs were halted because of
      high incidence of thromboembolic complications. Thus, we generated and
      characterized a fully human anti-CD40 mAb ASKP1240, as an alternative to anti
      CD154 mAb. In vitro ASKP1240 concentration-dependently inhibited human peripheral
      blood mononuclear cell proliferation induced by soluble CD154. In addition,
      ASKP1240 did not destabilize platelet thrombi under physiological high shear
      conditions while mouse anti-human CD154 mAb (mu5C8) did. And ASKP1240 itself did
      not activate platelet and endothelial cells. In vivo administration of ASKP1240
      (1 or 10 mg/kg, intravenously) to cynomolgus monkeys, weekly for 3 weeks,
      significantly attenuated both delayed-type hypersensitivity and specific antibody
      formation evoked by tetanus toxoid. The immunosuppressive effect was well
      correlated with the CD40 receptor saturation. Thus, these results suggest that
      ASKP1240 is immunosuppressive but not prothromboembolic, and as such appears to
      be a promising therapeutic candidate for the management of solid organ transplant
      rejection and autoimmune diseases therapy.

PMID- 24731052
TI  - Serum interleukin-17 as a diagnostic and prognostic marker for non-small cell
      lung cancer.
AB  - OBJECTIVE: The aim of this study was to explore the clinical role of serum
      interleukin (IL)-17 in patients with non-small-cell lung cancer (NSCLC).
      MATERIALS AND METHOD: Serum specimens from 128 patients with NSCLC and 60 healthy
      controls were collected. The concentrations of IL-17 were measured using enzyme
      linked immunosorbent assay. RESULTS: Serum IL-17 levels were higher in the NSCLC
      group in comparison with the control group (p < 0.01). With a cut-off value of 16
      pg/ml, IL-17 showed a good diagnostic performance for NSCLC. Multivariate
      survival analysis indicated that IL-17 was an independent prognostic factor in
      NSCLC. CONCLUSION: Measurement of IL-17 might be a useful diagnostic and
      prognostic value for patients with NSCLC.

PMID- 24731053
TI  - Thalidomide: Still an important second-line treatment in refractory cutaneous
      lupus erythematosus?
AB  - BACKGROUND: Cutaneous lupus erythematosus (CLE) can be a severe disease,
      characterized by extensive, disfiguring lesions and a relapsing course.
      Thalidomide is known as an effective treatment for CLE, however, its use is
      restricted by its potential side-effects. Nevertheless, it remains a valuable
      option to consider. Therefore, it is important to report new clinical
      experiences. METHODS: The data of 30 patients with refractory CLE, who were
      treated with thalidomide, were retrospectively analyzed. The response rate was
      categorized as complete, partial or no response. The relapse rate and the
      occurrence of side-effects were registered. RESULTS: Six patients prematurely
      discontinued treatment because of side-effects. The response rate was 100% in the
      remaining 24 patients, including 20 patients (83%) with complete response and 4
      (27%) with partial response. Clinical relapse was frequent (73%) and occurred
      between 3 and 24 weeks after withdrawal of thalidomide. Nine patients (30%)
      developed peripheral neuropathy. In the majority, there was no complete
      resolution of the neuropathy-associated symptoms after stopping thalidomide. One
      patient developed a thrombosis in an artery stent. CONCLUSION: Because of high
      risk of polyneuropathy, low-dose thalidomide should be used and long-term therapy
      should be avoided. Therefore, it should be recommended to combine thalidomide
      with other treatments for CLE.

PMID- 24731054
TI  - Fabrication of a highly b-oriented MFI-type zeolite film by the Langmuir-Blodgett
      method.
AB  - sec-Butanol-modified rounded-coffin-shaped silicalite-1 (SL) microcrystals were
      assembled into a compact and highly b-oriented monolayer extending over the
      centimeter scale via the Langmuir-Blodgett (LB) technique. For comparison,
      methanol- or ethanol-modified SL microcrystals could not float and were
      compressed into a dense film in an LB trough. Subsequently, highly b-oriented MFI
      films with a thickness of ~1.5 MUm were successfully obtained on the solid
      substrates by secondary growth of the LB monolayer using tetrapropylammonium
      hydroxide (TPAOH) as the structure-directing agent. The electrochemical
      experiments confirmed that the prepared films were defect-free. In general, the
      LB method is a highly controllable and reproducible method of organizing
      anisotropic zeolite crystals with a preferred orientation over a relatively large
      surface area. The LB technique could be further applied as an effective platform
      for the oriented assembly of different types of zeolite particles and the growth
      of variously oriented zeolite films. 

PMID- 24731055
TI  - Biodistribution of P-selectin targeted microbubbles.
AB  - PURPOSE: To evaluate binding of P-selectin targeted microbubbles (MB) in tumor
      vasculature; a whole-body imaging and biodistribution study was performed in a
      tumor bearing mouse model. METHODS: Antibodies were radiolabeled with Tc-99 m
      using the HYNIC method. Tc-99 m labeled anti-P-selectin antibodies were avidin
      bound to lipid-shelled, perfluorocarbon gas-filled MB and intravenously injected
      into mice bearing MDA-MB-231 breast tumors. Whole-body biodistribution was
      performed at 5 min (n = 12) and 60 min (n = 4) using a gamma counter. Tc-99 m
      labeled IgG bound IgG-control-MB group (n = 12 at 5 min; n = 4 at 60 min), Tc-99
      m-labeled IgG-control-Ab group (n = 5 at 5 min; n = 3 at 60 min) and Tc-99 m
      labeled anti P-selectin-Ab group (n = 5 at 5 min; n = 3 at 60 min) were also
      evaluated. Planar gamma camera imaging was also performed at each time point.
      RESULTS: Targeted-MB retention in tumor (60 min: 1.8 +/- 0.3% ID/g) was
      significantly greater (p = 0.01) than targeted-MB levels in adjacent skeletal
      muscle at both time points (5 min: 0.7 +/- 0.2% ID/g; 60 min: 0.2 +/- 0.1% ID/g)
      while there was no significant difference (p = 0.17) between muscle and tumor
      retention for the IgG-control-MB group at 5 min. CONCLUSIONS: P-selectin targeted
      MBs were significantly higher in tumor tissue, as compared with adjacent skeletal
      tissue or tumor retention of IgG-control-MB.

PMID- 24731056
TI  - Cellulose acetate phthalate microparticles containing Vibrio cholerae: steps
      toward an oral cholera vaccine.
AB  - Oral cholera vaccine (OCV) has been recommended in some endemic areas and
      epidemic situations since 1999. Although safe and effective vaccines are
      currently on the market, the burden of transport and storage remains an issue.
      Herein, we report an approach to develop an alternative OCV in the form of a
      gastro-resistant powder. Heat-killed Vibrio cholerae (VC) was encapsulated with a
      spray-drying technique at different temperatures. Cellulose acetate phthalate
      (Aquacoat(r) CPD) was chosen as the core polymer and the addition of alginate was
      studied. The microparticles (MPs) produced were characterized by surface
      morphology, particle size, drug loading, antigenicity and gastro resistance. The
      MPs obtained were 6 um in size and had appropriate drug content, ranging from
      8.16 to 8.64%. Furthermore, antigenicity was maintained, never dropping below
      85%, and enteric properties were achieved for all the formulations. Next, an in
      vivo study was carried out with Aquacoat(r) CPD MP prepared at 80  degrees C with
      and without alginate. Two different doses were assayed, 30 and 60 mg, and
      compared to the VC suspension. The evoked immune responses showed that alginate
      containing MPs, especially at the 30 mg dose, displayed values that were very
      similar to those of VC. In conclusion, spray-dried alginate VC MPs seem to be a
      promising step toward a powder-form cholera vaccination.

PMID- 24731057
TI  - Epithelial transport of noscapine across cell monolayer and influence of
      absorption enhancers on in vitro permeation and bioavailability: implications for
      intestinal absorption.
AB  - The purpose of this study was to investigate the permeation of Noscapine (Nos)
      across the Caco-2 and Madin-Darby canine kidney (MDCK) cell monolayers and to
      evaluate the influence of absorption enhancers on in vitro and in vivo absorption
      of Nos. The bidirectional transport of Nos was studied in Caco-2 and MDCK cell
      monolayers at pH 5.0-7.8. The effect of 0.5% w/v chitosan (CH) or Captisol (CP)
      on Nos permeability was investigated at pH 5.0 and 5.8. The effect of 1-5% w/v of
      CP on oral bioavailability of Nos (150 mg/kg) was evaluated in Sprague-Dawley
      rats. The effective permeability coefficients (Peff) of Nos across Caco-2 and
      MDCK cell monolayers was found to be in the order of pH 5.0 > 5.8 > 6.8 > 7.8.
      The efflux ratios of Peff < 2 demonstrated that active efflux does not limit the
      absorption of Nos. The use of CH or CP have shown significant (***, p < 0.001)
      enhancement in Peff of Nos across cell monolayer compared with the control group.
      The CP (1-5% w/v) based Nos formulations resulted in significant (***, p < 0.001)
      increase in the bioavailability of Nos compared with Nos solution. The use of CP
      represents viable approach for enhancing the oral bioavailability of Nos and
      reducing the required dose.

PMID- 24731058
TI  - Intracellular delivery of cytochrome c by galactosylated albumin to
      hepatocarcinoma cells.
AB  - In some cancer cells, translocation of cytochrome c (Cyt c) from mitochondria to
      the cytoplasma is inhibited. This inhibition prevents cells from undergoing
      apoptotic cell death and can lead to uncontrolled cell growth. Increasing
      cytoplasmic concentration of Cyt c can induce apoptosis in cancer cells as a
      strategy of cancer therapy. Here we proposed a galactosylated albumin based
      carrier for intracellular delivery of Cyt c to hepatocarcinoma cells.
      Galactosylated albumin is recognized by highly expressed asialoglycoprotein
      receptors (ASGPR) on hepatocarcinoma cells and is further internalized into cells
      via receptor mediated endocytosis. Cyt c was chemically conjugated to
      galactosylated albumin with a reducible disulfide linker in order to release Cyt
      c from the carrier inside cells. We tested cellular uptake and cytotoxicity of
      Cyt c conjugates in ASGPR positive and negative hepatocarcinoma cells. The
      results showed galatosylated albumin significantly increased cellular uptake in
      both cell types resulting in cytotoxicity in a dose dependent manner through the
      induction of apoptosis. The lack of ASGPR specific uptake might be due to other
      carbohydrate-recognizing receptors expressed on tumor cells. In general, our work
      has shown that intracellular delivery of Cyt c to tumor cells can be an
      alternative therapeutic approach and galactosylated albumin can be a protein drug
      carrier for intracellular delivery.

PMID- 24731059
TI  - Enhancement of antifungal activity by integrin-targeting of branched histidine
      rich peptides.
AB  - The treatment of invasive candidiasis associated with growing numbers of
      immunocompromised patients remains a major challenge complicated by increasing
      drug resistance. A novel class of branched histidine-lysine (bHK) peptides has
      promising antifungal activity, and exhibits a mechanism similar to natural
      histatins, and thus may avoid drug resistance. The present studies evaluate
      ligand targeting of bHK peptides to fungal surface integrins by determining
      whether a cyclic RGD (cRGD) peptide with a large PEG linker could enhance bHK
      peptide antifungal activity. Whereas conjugates containing only the PEG linker
      reduced bHK peptide activity, conjugates with the cRGD-PEG ligand resulted in
      marked enhancement of activity against Candida albicans. This study provides the
      first demonstration of benefit from ligand targeting of antifungal agents to
      fungal surface receptors.

PMID- 24731060
TI  - Two-dimensional microchemical observation of mast cell biogenic amine release as
      monitored by a 128 * 128 array-type charge-coupled device ion image sensor.
AB  - Available array-type, chemical-sensing image sensors generally only provide
      on/off responses to the sensed chemical and produce qualitative information.
      Therefore, there is a need for an array sensor design that can detect chemical
      concentration changes to produce quantitative, event-sensitive information. In
      this study, a 128 * 128 array-type image sensor was modified and applied to
      imaging of biogenic amines released from stimulated rat mast cells, providing
      recordable responses of the time course of their release and diffusion. The
      imaging tool was manufactured by an integrated circuit process, including
      complementary metal oxide semiconductor and charge-coupled device technology. It
      was fitted with an amine-sensitive membrane prepared from plasticized poly(vinyl
      chloride) including a hydrophobic anion, which allowed the sensor to detect
      amines, such as histamine and serotonin, in Tyrode's solution. As mast cells were
      larger in diameter than the pixel hollows, some pixels monitored amines released
      from single cells. The image from the array responses yielded sequential
      snapshots at a practical frame speed that followed amine concentration changes
      over time, after mast cell amine release was synchronized by chemical
      stimulation. This sensor was shown to be sensitive to amine release at very low
      stimulus concentrations and was able to detect localized spots of high amine
      release. The entire time course of the amine release was recorded, including
      maximum concentration at 4-6 s and signal disappearance at 30 s after
      stimulation. With further development, this sensor will increase opportunities to
      study a variety of biological systems, including neuronal chemical processes. 

PMID- 24731061
TI  - Comparison of tooth development stage of the maxillary anterior teeth before and
      after secondary alveolar bone graft: Unilateral cleft lip and alveolus vs
      unilateral cleft lip and palate.
AB  - OBJECTIVE: To compare the effect of secondary alveolar bone graft (SABG) on the
      tooth development stage of the maxillary central incisor (MXCI) and maxillary
      canine (MXC) in terms of the severity of unilateral cleft. MATERIALS AND METHODS:
      The subjects consisted of 50 boys with unilateral cleft lip and alveolus (UCLA)
      or unilateral cleft lip, alveolus, and palate (UCLP). The age- and sex-matched
      subjects were divided into group 1 (UCLA, n = 25; 9.3 +/- 0.8 years old) and
      group 2 (UCLP, n = 25; 9.4 +/- 0.6 years old). In panoramic radiographs taken 1
      month before (T0) and 1 year after SABG (T1), tooth development stage was
      evaluated according to the Nolla developmental (ND) stage. A panoramic radiograph
      taken 3 years after SABG was used as a reference for the final root length of
      individual tooth. RESULTS: In groups 1 and 2, the ND stage of the MXCI did not
      exhibit differences between the cleft and non-cleft sides at T0 and T1,
      respectively. However, although the ND stage of the MXC of group 2 was delayed on
      the cleft side compared with the non-cleft side at T0 (P < .05), the MXC on the
      cleft side developed faster than that on the non-cleft side after SABG (P < .01).
      In terms of tooth development speed, group 2 showed a higher rate of faster
      developed MXCs on the cleft side compared with the non-cleft side after SABG than
      group 1 (36.0% vs 8.0%, P < .05). CONCLUSION: SABG performed at approximately 9
      years of age might increase tooth development speed of MXC in patients with UCLP
      compared with patients with UCLA.

PMID- 24731062
TI  - Effect of the bracket types on microbial colonization and periodontal status.
AB  - OBJECTIVE: To evaluate the effect of different bracket types on the levels of
      Streptococcus mutans (SM) and Lactobacillus (LB) in saliva, in plaque, and on the
      periodontal condition. MATERIALS AND METHODS: Forty patients aged 14 to 16 years,
      who had Angle Class I malocclusion with minimal crowding, were nonsmokers, were
      without systematic disease, and did not use antibiotics or oral mouth rinses
      during the 3-month period before the study were randomly selected. The patients
      were subdivided into two groups with random allocation of bracket type:
      conventional brackets (CB; Avex Mx, OPAL orth.) with steel wire ligature or self
      ligating brackets (SLB; F1000, Leone S.p.A.). Microbial and periodontal records
      were obtained before bonding (T1) and 1 month after bonding (T2). Microbial
      samples were collected from the stimulated saliva and the plaque from the labial
      surfaces of the upper and lower lateral incisors. To estimate the number of
      colony-forming units of SM and LB, Dentocult SM and LB kits were used. The plaque
      index (PI), gingival index (GI), and pocket depth (PD) values were recorded to
      evaluate the periodontal condition. Paired t-test and Mann-Whitney U-test were
      used to compare the groups statistically. RESULTS: No significant differences
      occurred in SM or LB colonization between the groups. In the SLB group, PI, GI,
      and PD values increased significantly (P < .05). A greater increase was found in
      PD value in the SLB group (0.98 mm) compared with the CB group (0.04 mm; P <
      .05). CONCLUSIONS: The F1000 SLB do not have an advantage over Avex Mx CB with
      respect to periodontal status and colonization of SM and LB.

PMID- 24731064
TI  - Treatment of adult Class II division 2 patient with metal hypersensitivity.
AB  - This case report describes the orthodontic treatment of an adult female with an
      Angle Class II division 2 malocclusion with a severe deep bite and a congenitally
      missing lower incisor. The use of available orthodontic devices and materials was
      limited because the patient had metal allergies. Following a careful examination
      and case analysis, the preadjusted edgewise appliances and the microscrew
      implants were placed after the upper first premolars were extracted. After active
      treatment, a good facial profile and occlusion were achieved. These results have
      been maintained for 2 years following completion of the active treatment.

PMID- 24731063
TI  - Effect of Lithothamnium sp and calcium supplements in strain- and infection
      induced bone resorption.
AB  - OBJECTIVE: To investigate the effect of Lithothamnium sp (LTT) supplement, a
      calcium-rich alga widely used for mineral reposition, on strain-induced
      (orthodontic tooth movement [OTM]) and infection-induced bone resorption
      (periodontal disease [PD]) in mice. MATERIALS AND METHODS: Mice were divided into
      two bone resorption models: one with an orthodontic appliance and the other with
      PD induced by the oral inoculation of Aggregatibacter actinomycetencomitans (Aa).
      Both groups were fed a regular diet (vehicle), LTT-rich diet (LTT), or calcium
      rich diet (CaCO3). Alveolar bone resorption (ABR), the number of osteoclasts, and
      the levels of tumor necrosis factor alpha (TNF-alpha), calcium, and vitamin D3
      were evaluated. RESULTS: The number of osteoclasts was reduced in LTT and CaCO3
      mice, which led to diminished OTM and infection-induced alveolar bone loss. In
      addition, LTT- and calcium-treated groups also presented decreased levels of TNF
      alpha in periodontal tissues and increased levels of calcium in serum.
      CONCLUSIONS: These results indicate that the LTT supplement influences ABR,
      probably due to its calcium content, by affecting osteoclast function and local
      inflammatory response, thus modulating OTM and PD.

PMID- 24731065
TI  - Visual multifrequency entrainment: can 1:2, 2:3, and 3:4 coordination occur
      spontaneously?
AB  - Complex patterns of interlimb coordination, such as multifrequency relationships
      of 1:2, 2:3, or 3:4, are difficult to perform intentionally without extensive
      practice. The current study investigated whether these patterns might nonetheless
      occur spontaneously given an appropriate balance between the movement
      frequencies, or oscillatory periods, of an individual's movements and a visual
      environmental stimulus. In order to test this, participants swung a fixed-period
      wrist-pendulum while observing an oscillating computer-generated stimulus.
      Results indicated that at given differences in period, 1:2, 2:3, and 3:4
      coordination patterns emerged between the participant and stimulus. This suggests
      that large period differences do not altogether prevent the emergence of rhythmic
      visuomotor coordination, but instead provide the opportunity for complex patterns
      of coordination to emerge spontaneously.

PMID- 24731066
TI  - Population health: modest glycaemic improvements in a pregnant cohort with mild
      glucose intolerance decreased adverse outcomes.
AB  - BACKGROUND: Adverse perinatal outcomes are common with pregnancy-related mild
      glucose intolerance. The perinatal impact of improving this population's health,
      instead of individual health, has not been quantified. METHODS: We estimated this
      impact among women with mild glucose intolerance, delivered at The University of
      North Carolina Women's Hospital from April 1996 to May 2010. We compared observed
      with predicted risks of perinatal outcomes after simulating a cohort with a one
      standard deviation decrease in each glucose value. We estimated absolute and
      adjusted risks, relative risks, and risk differences with Poisson regression and
      bootstrapped 95% confidence intervals [CI]. RESULTS: Among 3217 women, mean (SD)
      1-h screening result was 157 (16) mg/dL; 3-h diagnostic results were 81 (10), 154
      (28), 130 (25), and 104 (26) mg/dL for fasting, 1-h, 2-h, and 3-h, respectively.
      Compared with observed, predicted risks decreased for preeclampsia (9.1% vs.
      6.6%, risk ratio [RR] 0.73 [95% CI 0.60, 0.88]), caesarean delivery (30.1% vs.
      26.4%, RR 0.88 [95% CI 0.81, 0.96]), preterm birth (13.0% vs. 9.8%, RR 0.75 [95%
      CI 0.64, 0.87]), birthweight >4000 g (13.4% vs. 10.5%, RR 0.78 [95% CI 0.67,
      0.90]), and shoulder dystocia (3.5% vs. 2.2%, RR 0.61 [95% CI 0.46, 0.83]).
      CONCLUSIONS: Modestly improved population distribution of glucose tolerance in
      pregnancies affected by mild glucose intolerance translated to meaningful
      improvements in perinatal outcomes.

PMID- 24731067
TI  - Gastric Helicobacter pylori infection associated with risk of diabetes mellitus,
      but not prediabetes.
AB  - BACKGROUNDS AND AIM: The association between Helicobacter pylori infection and
      diabetes was inconsistent in previous studies. Moreover, there are no studies on
      the relationship between H. pylori infection and prediabetes in the literature.
      The aim of this study is thus to assess the association of Helicobacter
      infection, diagnosed by pathology from gastric biopsy, with diabetes and
      prediabetes. METHODS: This cross-sectional study included 1285 subjects aged 19
      85 who underwent esophagogastroduodenoscopy and gastric biopsy during health
      examinations at National Cheng Kung University Hospital from 2000 to 2009.
      Subjects were divided into three groups, including normal glucose tolerance,
      prediabetes, and diabetes. Diabetes and prediabetes were assessed according to
      the American Diabetes Association diagnostic criteria. Gastric Helicobacter
      infection was an independent variable. Chi-square tests, analysis of variance,
      and multinomial logistic regression models were used to analyze the effects of
      Helicobacter infection on the risk of diabetes and prediabetes while controlling
      for age, lifestyle, pathological conditions, and laboratory variables. RESULTS:
      There were significant differences in the prevalence of gastric Helicobacter
      infection among the three groups. The results of multivariate analysis showed
      that age, obesity, family history of diabetes, hypertension, and
      hypertriglyceridemia were significantly related to both prediabetes and diabetes.
      Helicobacter pylori infection was positively associated with diabetes (odds ratio
      [OR] 1.42, 95% confidence interval [CI] 1.01-2.01), but not prediabetes (OR 1.02,
      95% CI 0.77-1.36), in addition to male gender, education level (<= 9 vs > 12
      years), pre-hypertension, and low high-density lipoprotein cholesterol.
      CONCLUSIONS: Gastric H. pylori infection is associated with diabetes, but not
      prediabetes.

PMID- 24731068
TI  - Final comments on the process: ILAE definition of epilepsy.

PMID- 24731069
TI  - A highly stable 3D acentric zinc metal-organic framework based on two symmetrical
      flexible ligands: high second-harmonic-generation efficiency and tunable
      photoluminescence.
AB  - A 3D metal-organic framework (MOF), [Zn(BPHY)(SA)]n (1; BPHY = 1,2-bis(4
      pyridyl)hydrazine, H2SA = succinic acid), which crystallizes in a
      noncentrosysmmetric space group (Cc), has been solvothermally obtained and
      testified to be a good nonlinear-optical material with the largest second
      harmonic-generation response among the known MOFs based on sysmmetric ligands and
      high stability. Ultraviolet-to-visible tunable emission for 1 is observed. 

PMID- 24731070
TI  - Timing of human chorionic gonadotropin (hCG) hormone administration in IVF/ICSI
      protocols using GnRH agonist or antagonists: a systematic review and meta
      analysis.
AB  - OBJECTIVE: To evaluate the effect of altering the timing of human chorionic
      gonadotropin (hCG) administration on the clinical outcome of in vitro
      fertilization (IVF) and intracytoplasmic sperm injection (ICSI) using
      gonadotropic hormone releasing hormone (GnRH) agonist or antagonist. METHODS: We
      systematically searched six databases. Randomized controlled trials (RCTs) of the
      effects of altering the timing of hCG administration on the clinical outcome of
      IVF and ICSI using GnRH agonist or antagonist were included. A meta-analysis was
      conducted following a quality evaluation performed with Cochrane Collaboration's
      Review Manager (RevMan) 5.0.2. RESULTS: Seven RCTs and a total of 1295
      participants were included. Significant difference was observed regarding
      estradiol and progesterone levels on the day of hCG administration and oocyte
      retrieval between early hCG and late hCG administration group and in favor of the
      latter. The fertilization rate was not statistically different between early and
      24-h late hCG groups, but it is significantly higher in the 48-h late hCG group.
      The pooled results showed no significant differences in the ongoing pregnancy
      rate per oocyte pick-up, the miscarriage rate and the live birth rate.
      CONCLUSION: The prolongation of follicular phase by delaying hCG administration
      could increase estradiol, progesterone levels and oocyte retrieval, which will
      not influence ongoing pregnancy rate per oocyte pick-up, miscarriage rate and
      live birth rate. Postponing hCG may enable increased flexibility of cycle
      scheduling to avoid weekend procedures.

PMID- 24731071
TI  - MUBII-TB-DB: a database of mutations associated with antibiotic resistance in
      Mycobacterium tuberculosis.
AB  - BACKGROUND: Tuberculosis is an infectious bacterial disease caused by
      Mycobacterium tuberculosis. It remains a major health threat, killing over one
      million people every year worldwide. An early antibiotic therapy is the basis of
      the treatment, and the emergence and spread of multidrug and extensively drug
      resistant mutant strains raise significant challenges. As these bacteria grow
      very slowly, drug resistance mutations are currently detected using molecular
      biology techniques. Resistance mutations are identified by sequencing the
      resistance-linked genes followed by a comparison with the literature data. The
      only online database is the TB Drug Resistance Mutation database (TBDReaM
      database); however, it requires mutation detection before use, and its
      interrogation is complex due to its loose syntax and grammar. DESCRIPTION: The
      MUBII-TB-DB database is a simple, highly structured text-based database that
      contains a set of Mycobacterium tuberculosis mutations (DNA and proteins)
      occurring at seven loci: rpoB, pncA, katG; mabA(fabG1)-inhA, gyrA, gyrB, and rrs.
      Resistance mutation data were extracted after the systematic review of MEDLINE
      referenced publications before March 2013. MUBII analyzes the query sequence
      obtained by PCR-sequencing using two parallel strategies: i) a BLAST search
      against a set of previously reconstructed mutated sequences and ii) the alignment
      of the query sequences (DNA and its protein translation) with the wild-type
      sequences. The post-treatment includes the extraction of the aligned sequences
      together with their descriptors (position and nature of mutations). The whole
      procedure is performed using the internet. The results are graphs (alignments)
      and text (description of the mutation, therapeutic significance). The system is
      quick and easy to use, even for technicians without bioinformatics training.
      CONCLUSION: MUBII-TB-DB is a structured database of the mutations occurring at
      seven loci of major therapeutic value in tuberculosis management. Moreover, the
      system provides interpretation of the mutations in biological and therapeutic
      terms and can evolve by the addition of newly described mutations. Its goal is to
      provide easy and comprehensive access through a client-server model over the Web
      to an up-to-date database of mutations that lead to the resistance of M.
      tuberculosis to antibiotics.

PMID- 24731072
TI  - Dose-dependent effects of an immune challenge at both ultimate and proximate
      levels in Drosophila melanogaster.
AB  - Immune responses are highly dynamic. The magnitude and efficiency of an immune
      response to a pathogen can change markedly across individuals, and such changes
      may be influenced by variance in a range of intrinsic (e.g. age, genotype, sex)
      and external (e.g. abiotic stress, pathogen identity, strain) factors. Life
      history theory predicts that up-regulation of the immune system will come at a
      physiological cost, and studies have confirmed that increased investment in
      immunity can reduce reproductive output and survival. Furthermore, males and
      females often have divergent reproductive strategies, and this might drive the
      evolution of sex-specific life history trade-offs involving immunity, and sexual
      dimorphism in immune responses per se. Here, we employ an experiment design to
      elucidate dose-dependent and sex-specific responses to exposure to a
      nonpathogenic immune elicitor at two scales--the 'ultimate' life history and the
      underlying 'proximate' immune level in Drosophila melanogaster. We found dose
      dependent effects of immune challenges on both male and female components of
      reproductive success, but not on survival, as well as a response in antimicrobial
      activity. These results indicate that even in the absence of the direct
      pathogenic effects that are associated with actual disease, individual life
      histories respond to a perceived immune challenge--but with the magnitude of this
      response being contingent on the initial dose of exposure. Furthermore, the
      results indicate that immune responses at the ultimate life history level may
      indeed reflect underlying processes that occur at the proximate level.

PMID- 24731073
TI  - Symptoms of autism and ADHD: a Swedish twin study examining their overlap.
AB  - Autism spectrum disorders (ASD) and attention deficit hyperactivity disorder
      (ADHD) show high comorbidity. The following questions were addressed regarding
      their specific symptoms: What is the factor structure of ASD and ADHD symptoms,
      to what degree do different symptom domains cluster together, to what extent are
      these domains caused by the same genetic and environmental influences, and what
      is the best model of their co-occurrence? A population-based twin cohort of over
      17,000 9- and 12-year-olds were assessed using the Autism-Tics, AD/HD, and other
      Comorbidities parental interview inventory. Principal component analyses were
      conducted, and symptom domain clustering was assessed. Four multivariate twin
      models were compared. Factors split into three ASD (social impairments,
      communication impairments, and restricted repetitive behaviors and interests),
      and three ADHD (inattention, hyperactivity, and impulsivity) symptom domains.
      Some ASD-ADHD symptom domain combinations clustered together often, although
      others not at all. A two-factor common pathway model fit the data, suggesting
      that ASD and ADHD symptom domains tap into separate "ASD" and "ADHD" latent
      factors that showed high genetic overlap. All subdomains also showed significant
      specific genetic and environmental influences, reflecting the etiological
      heterogeneity both within and between ASD and ADHD. These findings support the
      conceptual distinction of ASD and ADHD, and demonstrate the considerable natural
      co-occurrence of particular ASD/ADHD symptom domains. The results imply that more
      children with 1 condition show features of the other condition than show complete
      comorbidity. Emphasis on symptom co-occurrence, rather than complete comorbidity
      between disorders, may help focus clinical approaches and advance molecular
      genetic research.

PMID- 24731074
TI  - Response inhibition and psychopathology: a meta-analysis of go/no-go task
      performance.
AB  - Response inhibition, defined as the ability to withhold a response, is considered
      to be a core deficit in various mental illnesses. Measures of response inhibition
      have been used to define functional deficits, as markers of genetic risk, in
      neuroimaging studies, and for diagnostic purposes in these disorders. However,
      the magnitude of the deficit across psychopathologies has not been systematically
      assessed. We conducted a systematic review and meta-analysis of performance on
      commonly used measures of the ability to withhold a response: go/no-go task,
      Conners' continuous performance task (CCPT), and sustained attention to response
      task (SART). The primary variable of interest in each of these tasks was
      commission errors (CE), which provides an index of one's ability to correctly
      withhold a response. In addition, we examined omission errors (OE) which are an
      index of sustained attention; and mean reaction time (RT; MRT). Three-hundred and
      18 studies in 11 different psychiatric disorders met inclusion criteria. Weighted
      mean effect sizes (ESs) were calculated to measure the magnitude of the deficit.
      In general, we found low-to-medium ESs for commission errors ranging from g = 
      0.10 for anxiety disorder to medium ESs of g = 0.52 for bipolar disorder. Small
      to-medium deficits in withholding were found in various disorders. Results
      indicate that deficits in withholding are insufficiently sensitive or specific to
      be used individually as a diagnostic measure or biomarker in most disorders.

PMID- 24731075
TI  - Surface-induced conformational changes in doped bovine serum albumin self
      assembled monolayers.
AB  - Evidence for considerable stabilization of doped bovine serum albumin (BSA)
      molecules upon adsorption on gold surfaces is provided. This is compared to the
      surface-induced conformational changes of the bare BSA and its corresponding
      monolayer. The BSA unfolding phenomenon is correlated with dehydration, which in
      turn enables improved monolayer coverage. The stabilization mechanism is found to
      be partially controllable via nanodoping of the BSA molecules, upon which the
      dehydration process is suppressed and molecular rigidity can be varied. Our
      experimental data and calculations further point to the intermixing of structural
      characteristics and inherent molecular properties in studies of biological
      monolayers. 

PMID- 24731076
TI  - Paroxysmal sympathetic hyperactivity after acquired brain injury: consensus on
      conceptual definition, nomenclature, and diagnostic criteria.
AB  - A syndrome of paroxysmal, episodic sympathetic hyperactivity after acquired brain
      injury has been recognized for almost 60 years. This project sought to simplify
      the confused nomenclature for the condition (>31 eponyms) and simplify the nine
      overlapping sets of diagnostic criteria. A consensus-developed questionnaire
      based on a systematic review of the literature was circulated to a widely
      representative, international expert group utilizing a Delphi approach.
      Diagnostic criteria were dropped if group consensus failed to agree on their
      relative importance, with a goal of reaching a Cronbach alpha of 0.8 (suitable
      for research purposes). The resulting criteria were combined into an assessment
      measure for clinical and research settings. The consensus group recommend that
      the term "paroxysmal sympathetic hyperactivity" replace previous terms to
      describe the "syndrome, recognised in a subgroup of survivors of severe acquired
      brain injury, of simultaneous, paroxysmal transient increases in sympathetic
      [elevated heart rate, blood pressure, respiratory rate, temperature, sweating]
      and motor [posturing] activity." An 11 point probabilistic diagnostic scale was
      developed with reference to published criteria, yielding an acceptable Cronbach
      alpha of 0.8. These 11 items were proceduralized and combined with a symptom
      severity index to produce a diagnostic tool for use with adults (the paroxysmal
      sympathetic hyperactivity assessment measure [PSH-AM]). Development of a
      pediatric version of the scale and further research into the validity of the PSH
      AM is recommended. The consensus position builds on previous literature to
      establish diagnostic definitions and criteria, an important move to standardize
      research and management of this condition.

PMID- 24731077
TI  - Impact of spatial resolution on results of esophageal high-resolution manometry.
AB  - BACKGROUND: The Chicago classification for esophageal motility disorders was
      designed for a 36-channel manometry system with sensors spaced at 1 cm. However,
      many motility laboratories outside the USA use catheters with a lower resolution
      in the segments outside the esophagogastric junction. Our aim was to investigate
      the effect of spatial resolution on the Chicago metrics and diagnosis. METHODS:
      In 20 healthy volunteers and 47 patients with upper gastrointestinal symptoms,
      high-resolution manometric studies of the esophagus were retrospectively
      reanalyzed using the original 1-cm spacing in the segments outside the 7-cm
      esophagogastric junction segment, and again after manually increasing the spacing
      between sensors to 2, 3, and 4 cm (above the lower esophageal sphincter region).
      Measurements were analyzed in random order and the investigator was blinded to
      the outcome of the analyses performed in another resolution of the same patient.
      Intra-class correlation coefficients (ICC) and Kappa values were determined. KEY
      RESULTS: There was a very strong correlation between the 1-cm and 2-cm analysis
      for all Chicago metrics studied in healthy volunteers (ICCs: distal contractile
      integral 0.998; contractile front velocity (CFV) 0.964; distal latency 0.919;
      peristaltic break size 0.941). The 2-cm spacing analysis also correlated very
      well with the 1-cm analysis for the different Chicago diagnoses obtained in the
      patients (Kappa values ranging from 0.665 to 1.000). When the sensor spacing was
      increased to 3 and 4 cm, the correlation was reduced to moderate for the Chicago
      metrics, especially for break size and CFV of peristalsis. CONCLUSIONS &
      INFERENCES: The Chicago classification for esophageal motility disorders is still
      valid and the same normal values can be used when catheters with a slightly lower
      resolution are used (i.e., 2-cm vs 1-cm spacing). For larger sensor intervals,
      the classification and the normal values will need to be adjusted.

PMID- 24731078
TI  - Aberrant neural responses to social rejection in patients with schizophrenia.
AB  - Patients with schizophrenia often show abnormal social interactions, which may
      explain their social exclusion behaviors. This study aimed to elucidate patients'
      brain responses to social rejection in an interactive situation. Fifteen patients
      with schizophrenia and 16 healthy controls participated in the functional
      magnetic resonance imaging experiment with the virtual handshake task, in which
      socially interacting contents such as acceptance and refusal of handshaking were
      implemented. Responses to the refusal versus acceptance conditions were evaluated
      and compared between the two groups. Controls revealed higher activity in the
      refusal condition compared to the acceptance condition in the right superior
      temporal sulcus, whereas patients showed higher activity in the prefrontal
      regions, including the frontopolar cortex. In patients, contrast activities of
      the right superior temporal sulcus were inversely correlated with the severity of
      schizophrenic symptoms, whereas contrast activities of the left frontopolar
      cortex were positively correlated with the current anxiety scores. The superior
      temporal sulcus hypoactivity and frontopolar hyperactivity of patients with
      schizophrenia in social rejection situations may suggest the presence of
      mentalizing deficits in negative social situations and inefficient processes of
      socially aberrant stimuli, respectively. These abnormalities may be one of the
      neural bases of distorted or paranoid beliefs in schizophrenia.

PMID- 24731079
TI  - Diagnostic performance and safety of a three-dimensional 14-core systematic
      biopsy method.
AB  - OBJECTIVE: To investigate the diagnostic performance and safety of a three
      dimensional 14-core biopsy (3D14PBx) method, which is a combination of the
      transrectal six-core and transperineal eight-core biopsy methods. PATIENTS AND
      METHODS: Between December 2005 and August 2010, 1103 men underwent 3D14PBx at our
      institutions and were analysed prospectively. Biopsy criteria included a PSA
      level of 2.5-20 ng/mL or abnormal digital rectal examination (DRE) findings, or
      both. The primary endpoint of the study was diagnostic performance and the
      secondary endpoint was safety. We applied recursive partitioning to the entire
      study cohort to delineate the unique contribution of each sampling site to
      overall and clinically significant cancer detection. RESULTS: Prostate cancer was
      detected in 503 of the 1103 patients (45.6%). Age, family history of prostate
      cancer, DRE, PSA, percentage of free PSA and prostate volume were associated with
      the positive biopsy results significantly and independently. Of the 503 cancers
      detected, 39 (7.8%) were clinically locally advanced (>=cT3a), 348 (69%) had a
      biopsy Gleason score (GS) of >=7, and 463 (92%) met the definition of biopsy
      based significant cancer. Recursive partitioning analysis showed that each
      sampling site contributed uniquely to both the overall and the biopsy-based
      significant cancer detection rate of the 3D14PBx method. The overall cancer
      positive rate of each sampling site ranged from 14.5% in the transrectal far
      lateral base to 22.8% in the transrectal far lateral apex. As of August 2010, 210
      patients (42%) had undergone radical prostatectomy, of whom 55 (26%) were found
      to have pathologically non-organ-confined disease, 174 (83%) had prostatectomy GS
      >=7 and 185 (88%) met the definition of prostatectomy-based significant cancer.
      CONCLUSIONS: This is the first prospective analysis of the diagnostic performance
      of an extended biopsy method, which is a simplified version of the somewhat
      redundant super-extended three-dimensional 26-core biopsy. As expected, each
      sampling site uniquely contributed not only to overall cancer detection, but also
      to significant cancer detection. 3D14PBx is a feasible systematic biopsy method
      in men with PSA <20 ng/mL.

PMID- 24731080
TI  - Markers of topical discourse in child-directed speech.
AB  - Although the language we encounter is typically embedded in rich discourse
      contexts, many existing models of processing focus largely on phenomena that
      occur sentence-internally. Similarly, most work on children's language learning
      does not consider how information can accumulate as a discourse progresses.
      Research in pragmatics, however, points to ways in which each subsequent
      utterance provides new opportunities for listeners to infer speaker meaning. Such
      inferences allow the listener to build up a representation of the speakers'
      intended topic and more generally to identify relationships, structures, and
      messages that extend across multiple utterances. We address this issue by
      analyzing a video corpus of child-caregiver interactions. We use topic continuity
      as an index of discourse structure, examining how caregivers introduce and
      discuss objects across utterances. For the analysis, utterances are grouped into
      topical discourse sequences using three annotation strategies: raw annotations of
      speakers' referents, the output of a model that groups utterances based on those
      annotations, and the judgments of human coders. We analyze how the lexical,
      syntactic, and social properties of caregiver-child interaction change over the
      course of a sequence of topically related utterances. Our findings suggest that
      many cues used to signal topicality in adult discourse are also available in
      child-directed speech. 

PMID- 24731081
TI  - Treatment of various types of basal cell carcinoma with topical 5% imiquimod in
      the elderly who refused surgical intervention: a case series.
AB  - Basal cell carcinoma (BCC) is the most common non-melanoma skin cancer in the
      elderly population, causing significant local destruction and image deformities.
      Although surgical excision is the primary treatment modality, preservation of
      functions, cosmetic concerns and patient's age, as well as tumor prognostic
      factors, aid in treatment selection. Topical imiquimod provides immunomodulatory
      effects by increasing the release of proinflammatory cytokines, and is currently
      approved and funded for pathologically diagnosed superficial BCC. We report
      herein the successful results of topical imiquimod in four cases of BCC, nodular
      and large superficial types, all of whom refused surgical intervention. The
      lesions regressed in all except one in whom more than one BCC of superficial type
      was present. She is still on follow-up for intermittent cryotherapy sessions.
      Imiquimod is a good alternative to surgery in elderly patients who have
      unwillingness to surgery and are often poor candidates for surgery. 

PMID- 24731082
TI  - Governance, stewardship and cosmetics.

PMID- 24731083
TI  - Outbreak of contact sensitization to methylisothiazolinone: an analysis of French
      data from the REVIDAL-GERDA network.
AB  - BACKGROUND: The preservative methylisothiazolinone (MI) is used in combination
      with methylchloroisothiazolinone (MCI), but the MCI/MI mixture has been
      identified as highly allergenic. MI is considered to be less allergenic, and
      since the mid-2000s has been widely used alone, but is now clearly identified as
      a contact allergen. The French Vigilance Network for Dermatology and Allergy of
      the Study and Research Group on Contact Dermatitis (REVIDAL-GERDA) added MI to
      its baseline patch testing series in 2010. OBJECTIVE: To evaluate the change in
      the proportion of MI-positive tests in France between 2010 and 2012.
      PATIENTS/MATERIALS/METHODS: We conducted a nationwide, multicentre, retrospective
      study of all MI-tested patients between 2010 and 2012. RESULTS: Sixteen centres
      participated in the study (7874 patients were tested). Patch tests were performed
      mainly at a concentration of MI 200 ppm aq. We observed a significant increase in
      the proportion of MI-positive tests in 2012 and 2011 as compared with 2010 (5.6%,
      3.3%, and 1.5%, respectively; p < 0.001). CONCLUSIONS: We report a significant
      increase in the number of MI-positive tests. MI is confirmed to be a rapidly
      emerging allergen, as also observed in other European countries.

PMID- 24731084
TI  - Baseline series fragrance markers fail to predict contact allergy.
AB  - BACKGROUND: Negative patch test results with fragrance allergy markers in the
      European baseline series do not always predict a negative reaction to individual
      fragrance substances. OBJECTIVES: To determine the frequencies of positive test
      reactions to the 26 fragrance substances for which labelling is mandatory in the
      EU, and how effectively reactions to fragrance markers in the baseline series
      predict positive reactions to the fragrance substances that are labelled.
      METHODS: The records of 1951 eczema patients, routinely tested with the labelled
      fragrance substances and with an extended European baseline series in 2011 and
      2012, were retrospectively reviewed. RESULTS: Two hundred and eighty-one (14.4%)
      (71.2% females) reacted to one or more allergens from the labelled-fragrance
      substance series and/or a fragrance marker from the European baseline series. The
      allergens that were positive with the greatest frequencies were cinnamyl alcohol
      (48; 2.46%), Evernia furfuracea (44; 2.26%), and isoeugenol (40; 2.05%). Of the
      203 patients who reacted to any of the 26 fragrances in the labelled-fragrance
      substance series, only 117 (57.6%) also reacted to a fragrance marker in the
      baseline series. One hundred and seven (52.7%) reacted to either fragrance mix I
      or fragrance mix II, 28 (13.8%) reacted to Myroxylon pereirae, and 13 (6.4%)
      reacted to hydroxyisohexyl 3-cyclohexene carboxaldehyde. CONCLUSIONS: These
      findings confirm that the standard fragrance markers fail to identify patients
      with contact allergies to the 26 fragrances.

PMID- 24731085
TI  - Reaction profile in patch testing with allergens formed during vulcanization of
      rubber.
AB  - BACKGROUND: Vulcanization of rubber changes its allergen pattern. OBJECTIVES: To
      estimate the contact allergic reactivity profile of users of finished rubber
      products. METHODS: Twenty-four patients with known contact allergy to rubber
      accelerators were patch tested with 21 compounds found in chemical analyses of
      vulcanized rubber products. No diphenylguanidine, p-phenylenediamine antioxidants
      or thioureas were included in the study. RESULTS: Thiuram monosulfides formed
      during vulcanization showed generally stronger test reactions than the
      corresponding thiuram disulfides. We also obtained more positive thiuram
      reactions to the monosulfides than to the disulfides. A positive reaction to a
      dithiocarbamate was accompanied by a positive reaction to the corresponding
      thiuram, except for 1 patient. The nitrogen substituents showed only minor
      differences between the methyl, ethyl and pentamethylene groups, but the butyl
      derivatives gave, in most cases, a negative response. Dialkylthiocarbamyl
      benzothiazole sulfides, formed between thiurams and mercaptobenzothiazoles during
      vulcanization, showed strong test reactions in almost all patients who were
      sensitive to dithiocarbamates, thiurams, or mercaptobenzothiazoles. CONCLUSIONS:
      We found thiuram monosulfides to be better markers of thiuram sensitivity than
      the corresponding disulfides or dithiocarbamates. Surprisingly, the
      dialkylthiocarbamyl benzothiazole sulfides were good markers of both thiuram and
      mercaptobenzothiazole sensitivity. This is an unexpected finding that needs to be
      confirmed in a larger study.

PMID- 24731086
TI  - Concentrations and stability of methyl methacrylate, glutaraldehyde, formaldehyde
      and nickel sulfate in commercial patch test allergen preparations.
AB  - BACKGROUND: Epicutaneous patch tests are used to reproduce allergy and diagnose
      allergic contact dermatitis. Reliable allergen test preparations are required.
      OBJECTIVES: The purpose of the present study was to measure the actual
      concentrations of nickel(II) sulfate hexahydrate (NiSO4 ), methyl methacrylate,
      formaldehyde, and glutaraldehyde, and to compare them with the labelled
      concentrations, in commercial patch test allergen preparations found in
      dermatology clinics where patch testing is routinely performed. MATERIALS AND
      METHODS: The commercial in-date and out-of-date patch test allergen preparations
      concentrations of NiSO4 , methyl methacrylate, formaldehyde and glutaraldehyde
      from one to three participating clinics were analysed with chromatographic or wet
      chemical techniques. RESULTS: NiSO4 and formaldehyde concentrations were at or
      above the labelled concentrations; however, formaldehyde loss occurred with
      storage. NiSO4 particulate was uniformly distributed throughout the petrolatum.
      'In-use' methyl methacrylate reagent syringes all contained <= 56% of the 2%
      label concentration, with no observable relationship with expiration date. Lower
      methyl methacrylate cocentrations were consistently measured at the syringe tip
      end, suggesting loss resulting from methyl methacrylate's volatility. The
      concentrations of glutaraldehyde patch test allergen preparations ranged from 27%
      to 45% of the labelled (1% in pet.) concentration, independently of expiration
      date. CONCLUSIONS: Some false-negative methyl methacrylate, formaldehyde or
      glutaraldehyde patch test results may be attributable to instability of the test
      preparations.

PMID- 24731087
TI  - Escalating methylisothiazolinone/methylchloroisothiazolinone allergy probably
      attributable to methylisothiazolinone in leave-on body cosmetics.

PMID- 24731088
TI  - Multicentre patch testing with methylisothiazolinone by the European
      Environmental and Contact Dermatitis Research Group.

PMID- 24731089
TI  - Presumed airborne contact allergy to methylisothiazolinone causing acute severe
      facial dermatitis and respiratory difficulty.

PMID- 24731090
TI  - Severe occupational chromium allergy despite cement legislation.

PMID- 24731091
TI  - Polyhexamethylene biguanide is a relevant sensitizer in wet wipes.

PMID- 24731092
TI  - Tricresyl phosphate in polyvinylchloride gloves: a new allergen.

PMID- 24731093
TI  - Current practice of methotrexate use for psoriasis: results of a worldwide survey
      among dermatologists.
AB  - BACKGROUND: Methotrexate is one the most commonly used systemic therapies for
      psoriasis. Despite its widespread use in psoriasis therapy, dermatologists'
      practice regarding the use of methotrexate has not been investigated on global
      scale. OBJECTIVE: To evaluate the real life use of methotrexate for psoriasis
      treatment in the dermatological community worldwide. METHODS: A questionnaire
      consisting of 41 questions was designed by the Psoriasis International Network
      (PIN). Questions focused on safety, dosing, administration, folic acid
      supplementation and combination therapy aspects of methotrexate use. The
      anonymous web-based survey was distributed to dermatologists by the national
      coordinators of PIN. RESULTS: Between 2 April and 7 August 2012, 481
      dermatologists from 63 countries completed the questionnaire. Most respondents
      were from European and South American countries, whereas the response rate from
      Central America and the Near East was lowest. The majority of responders were
      experienced dermatologists (86% had more than 5 years of experience in psoriasis
      treatment). Starting and maintenance doses of 10 mg of methotrexate or lower were
      reported by 67% and 42% of respondents respectively. Thirty-eight per cent of
      respondents stop treatment at a cumulative dose of 2 g, whereas 36% did not
      consider cumulative dose important in this respect. The primary mode of
      administration was oral, and the majority of respondents administer folic acid
      supplementation. Almost all respondents monitored full blood count, liver and
      renal function tests, whereas procollagen 3 amino terminal peptide measurement
      and transient elastography is used by only a minority of dermatologists. There
      were significant differences concerning the doses, routes of administration and
      safety monitoring among the clinical practices in different geographical
      locations. CONCLUSION: Current clinical practice of methotrexate use in psoriasis
      is not uniform, depends on geographical location, and is not in full agreement
      with clinical guidelines.

PMID- 24731094
TI  - Treatment approach, surveillance, and outcome of well-differentiated thyroid
      cancer in childhood and adolescence.
AB  - BACKGROUND: Well-differentiated thyroid carcinoma in children and adolescents is
      a rare disease with favorable prognosis despite regional and distant metastasis
      at presentation in many patients. Treatment recommendations are varied and there
      is little consensus on follow-up guidelines for these patients. METHODS: Medical
      records of patients less than 22 years of age treated at our institution were
      reviewed. One hundred twelve patients treated between 1969 and 2009 were selected
      for further analysis. Effects of patient and tumor characteristics on progression
      free survival (PFS) were evaluated along with the predictive value of whole-body
      (131)I scintigraphy in the follow-up setting. RESULTS: Overall survival at 20
      years and 30 years was 100% and 94.4%, respectively. PFS at 10, 20, and 30 years
      was 71%, 62%, and 55%, respectively. Although male patients and younger patients
      presented with more advanced disease, sex, and age at diagnosis had no effect on
      risk of PFS. Additionally, neither the presence of vascular invasion, capsular
      extension, positive margins, nor soft tissue invasion had an effect on PFS. Mean
      time to recurrence in patients who underwent immediate postoperative (131)I
      therapy was 3.8 years compared to 14.1 years in patients who either never
      received (131)I therapy or were treated in the salvage setting (p<0.0001).
      Negative posttreatment whole-body (131)I scintigraphy was strongly predictive for
      decreased risk of recurrence, especially in patients with three consecutive
      negative scans. CONCLUSIONS: Pediatric patients are more likely to present with
      advanced disease and for this reason, the majority of patients treated at our
      institution receive postoperative (131)I. Long-term surveillance is required in
      this population because of the risk of late recurrences. Whole-body (131)I
      scintigraphy is useful for risk stratification; after three consecutive negative
      scans, the risk of recurrence is low.

PMID- 24731095
TI  - Life-space mobility declines associated with incident falls and fractures.
AB  - OBJECTIVES: To determine the effect of falls and fractures on life-space mobility
      in a cohort of community-dwelling older adults. DESIGN: Prospective,
      observational study with a baseline in-home assessment and 6-month telephone
      follow-up interviews over 4 years. SETTING: Central Alabama. PARTICIPANTS:
      Community-dwelling adults aged 65 and older recruited from a random sample of
      Medicare beneficiaries stratified according to sex, race, and urban versus rural
      residence (N = 970). MEASUREMENTS: Sociodemographic factors, medical history,
      depressive symptoms (Geriatric Depression Scale), cognitive function (Mini-Mental
      State Examination), mobility-related symptoms, transportation difficulty, and
      healthcare use were assessed during a baseline in-home interview of participants.
      Life-space mobility and falls or injuries (including fractures) were assessed at
      the baseline interview and at 6-month intervals in follow-up telephone calls.
      RESULTS: Four hundred fifty-four (47%) participants reported at least one fall
      during the 4-year follow-up. The life-space score fell 3.2 points from the
      beginning to the end of the 6-month interval during which a fall occurred,
      adjusting for other known predictors of decline in life-space mobility. The
      decrease in interval life-space score was progressively greater for a fall and an
      injury (-4.7 points), a fall and a fracture (-14.2 points), and a fall and a hip
      fracture (-23.6 points). CONCLUSION: Falls, whether associated with an injury or
      not, were independently associated with a decrease in life-space mobility in the
      ensuing 6 months. Further studies are needed to determine reasons for life-space
      mobility decline in community-dwelling older adults with incident falls without
      any injuries.

PMID- 24731096
TI  - Corticotropin-releasing hormone and the sympathoadrenal system are major
      mediators in the effects of peripherally administered exendin-4 on the
      hypothalamic-pituitary-adrenal axis of male rats.
AB  - Glucagon-like peptide-1 (GLP-1) and the GLP-1 receptor agonist, exendin-4 (Ex-4),
      potently stimulate hypothalamic-pituitary-adrenal (HPA) axis activity after
      either central or peripheral administration. Because several GLP-1 derivative
      drugs, including synthetic Ex-4, are currently in use to treat patients with type
      II diabetes mellitus, the characterization of Ex-4 effects on the HPA axis is
      highly relevant. Herein, the roles of CRH and AVP on these effects were
      investigated by administering the antagonists astressin and d(CH2)5Tyr(Me)AVP,
      respectively. The role of the sympathoadrenal system (SAS) was explored in
      bilateral adrenal enucleated and guanethidine-treated rats, whereas primary
      pituitary cell cultures were used to study direct effects on the corticotropes.
      Astressin completely abrogated (P < .05) the effects of Ex-4 central
      administration on ACTH secretion but only slightly reduced (by 35%) the ACTH
      response to Ex-4 peripheral administration. Moreover, astressin significantly (P
      < .05) decreased the corticosterone response to centrally but not peripherally
      administered Ex-4, suggesting different mechanisms depending on the route of
      administration. Pretreatment with d(CH2)5Tyr(Me)AVP failed to diminish either the
      ACTH or corticosterone response to Ex-4 and no direct effect of Ex-4 or GLP-1 was
      observed on pituitary cell cultures. In contrast, a significant (P < .05)
      reduction in the corticosterone response elicited by Ex-4 peripheral
      administration was observed in enucleated and guanethidine-treated rats,
      indicating a role of the SAS in the glucocorticoid stimulatory effects of Ex-4.
      Our data demonstrate that the effects of Ex-4 on the HPA axis are partially
      mediated by CRH and the sympathoadrenal system, and stress the relevance of Ex-4
      as a corticosterone secretagogue. 

PMID- 24731098
TI  - A novel role for the thyroid hormone-activating enzyme type 2 deiodinase in the
      inflammatory response of macrophages.
AB  - Deiodinase type 2 (D2) is a thyroid hormone-activating enzyme converting the
      prohormone T4 into the active hormone T3. In the present study, we show for the
      first time that D2 is up-regulated in the mouse liver during acute and chronic
      inflammation, in close correlation with the proinflammatory cytokine IL-1beta and
      independently of serum T3. Inflammation-induced D2 expression was confirmed in
      macrophages, in conjunction with selective thyroid hormone transporter
      (monocarboxylate transporter 10) and thyroid hormone receptor (TR)alpha1
      stimulation, and was absent in hepatocytes. Moreover, D2 knockdown in macrophages
      resulted in a clear attenuation of the lipopolysaccharide (LPS)-induced IL-1beta
      and GM-CSF expression, in addition to aberrant phagocytosis. Locally produced T3,
      acting via the TRalpha, may be instrumental in this novel inflammatory response,
      because LPS-treated TRalpha(0/0) mice showed a markedly decreased LPS-induced GM
      CSF mRNA expression. We now propose that hepatic D2 favors the innate immune
      response by specifically regulating cellular thyroid hormone levels in
      macrophages. 

PMID- 24731097
TI  - Essential roles of epithelial bone morphogenetic protein signaling during
      prostatic development.
AB  - Prostate is a male sex-accessory organ. The prostatic epithelia consist primarily
      of basal and luminal cells that differentiate from embryonic urogenital sinus
      epithelia. Prostate tumors are believed to originate in the basal and luminal
      cells. However, factors that promote normal epithelial differentiation have not
      been well elucidated, particularly for bone morphogenetic protein (Bmp)
      signaling. This study shows that Bmp signaling prominently increases during
      prostatic differentiation in the luminal epithelia, which is monitored by the
      expression of phosphorylated Smad1/5/8. To elucidate the mechanism of epithelial
      differentiation and the function of Bmp signaling during prostatic development,
      conditional male mutant mouse analysis for the epithelial-specific Bmp receptor
      1a (Bmpr1a) was performed. We demonstrate that Bmp signaling is indispensable for
      luminal cell maturation, which regulates basal cell proliferation. Expression of
      the prostatic epithelial regulatory gene Nkx3.1 was significantly reduced in the
      Bmpr1a mutants. These results indicate that Bmp signaling is a key factor for
      prostatic epithelial differentiation, possibly by controlling the prostatic
      regulatory gene Nkx3.1. 

PMID- 24731099
TI  - Genetic background defines the regulation of postnatal cardiac growth by 17beta
      estradiol through a beta-catenin mechanism.
AB  - Estrogen regulates several biological processes in health and disease.
      Specifically, estrogen exerts antihypertrophic effects in the diseased heart.
      However, its role in the healthy heart remains elusive. Our initial aim was to
      identify the effects of 17beta-estradiol (E2) on cardiac morphology and global
      gene expression in the healthy mouse heart. Two-month-old C57BL/6J mice were
      ovariectomized and treated with E2 or vehicle for 3 months. We report that E2
      induced physiological hypertrophic growth in the healthy C57BL/6J mouse heart
      characterized by an increase in nuclear beta-catenin. Hypothesizing that beta
      catenin mediates these effects of E2, we employed a model of cardiac beta-catenin
      deletion. Our surprising finding is that E2 had the opposite effects in wild-type
      littermates, which were actually on the C57BL/6N background. Notably, E2 exerted
      no significant effect in hearts of mice with depleted beta-catenin. We further
      demonstrate an E2-dependent increase in glycogen synthase kinase 3beta (GSK3beta)
      phosphorylation and endosomal markers in C57BL/6J but not C57BL/6N mice.
      Together, these findings indicate an E2-driven inhibition of GSK3beta and
      consequent activation of beta-catenin in C57BL/6J mice, whereas the opposite
      occurs in C57BL/6N mice. In conclusion, E2 exerts divergent effects on postnatal
      cardiac growth in mice with distinct genetic backgrounds modulating members of
      the GSK3beta/beta-catenin cascade. 

PMID- 24731101
TI  - Risk factors for retransplant kidney recipients: relisting and outcomes from
      patients' primary transplant.
AB  - As of November 2013, 14.5% of the waitlist for a donor kidney comprised patients
      awaiting a retransplant. We performed a retrospective cohort study of 11,698
      adult solitary kidney recipients using national Scientific Registry of Transplant
      Recipients data transplanted between 2002 and 2011. The aim was to investigate
      whether outcomes from patients' initial transplants are significant risk factors
      for patients' repeat transplants or for likelihood of relisting after a failed
      primary transplant. Retransplant recipients were more likely to be treated for
      acute rejection [adjusted odds ratio (AOR), 95% confidence interval (CI) = 1.26
      (1.07-1.48), p = 0.0053] or hospitalized (AOR = 1.19, 95% CI 1.08-1.31, p =
      0.0005) within a year of retransplantation if these outcomes were experienced
      within a year of primary transplant. Delayed graft function following primary
      transplants was associated with 35% increased likelihood of recurrence (AOR =
      1.35, 95% CI = 1.18-1.54, p < 0.0001). An increase in 1-year GFR after primary
      transplant was associated with GFR 1 year postretransplant (beta = 6.82, p <
      0.0001), and retransplant graft failure was inversely associated with 1-year
      primary transplant GFR (adjusted hazard ratio = 0.74, 95% CI = 0.71-0.76 per 10
      mL/min/1.73 m(2) ). A decreased likelihood for relisting was associated with
      hospitalization and higher GFR following primary transplantation. The increasing
      numbers of individuals requiring retransplants highlights the importance of
      incorporating prior transplant outcomes data to better inform relisting decisions
      and prognosticating retransplant outcomes.

PMID- 24731100
TI  - Dietary sugar in healthy female primates perturbs oocyte maturation and in vitro
      preimplantation embryo development.
AB  - The consumption of refined sugars continues to pose a significant health risk.
      However, nearly nothing is known about the effects of sugar intake by healthy
      women on the oocyte or embryo. Using rhesus monkeys, we show that low-dose
      sucrose intake over a 6-month period has an impact on the oocyte with subsequent
      effects on the early embryo. The ability of oocytes to resume meiosis was
      significantly impaired, although the differentiation of the somatic component of
      the ovarian follicle into progesterone-producing cells was not altered. Although
      the small subset of oocytes that did mature were able to be fertilized in vitro
      and develop into preimplantation blastocysts, there were >1100 changes in
      blastocyst gene expression. Because sucrose treatment ended before fertilization,
      the effects of sugar intake by healthy primates are concluded to be epigenetic
      modifications to the immature oocyte that are manifest in the preimplantation
      embryo. 

PMID- 24731103
TI  - Preparation and catalytic activity of Pd and bimetallic Pd-Ni nanowires.
AB  - This article describes the preparation and catalytic property of Pd and Pd-Ni
      nanowires with network structure. A soft template with network structure formed
      by long-chain amidoamine derivative (C18AA) was essential to preparing Pd and Pd
      Ni nanowires because of the preparation of only spherical nanoparticles using
      octadecylamine, which does not form a network structure as a soft template,
      instead of C18AA. Furthermore, this soft-template method demands a slow reduction
      rate for the metal ion, the same as the general preparation method for novel
      metal nanowires. The distinguishing features of the present method is that the
      nanowires are a few nanometers in diameter and there are no byproducts such as
      nanoparticles. In addition, the bimetallic Pd-Ni nanowires show very high
      catalytic activity for the hydrogenation of p-nitrophenol as compared to Pd
      nanowires, Pd nanoparticles, and Pd-Ni nanoparticles. 

PMID- 24731102
TI  - Patterns and predictors of antiretroviral therapy use among alcohol drinkers at
      HIV clinics in Tshwane, South Africa.
AB  - Alcohol use is associated with compromised antiretroviral therapy (ART)
      adherence. We aimed to identify patterns and predictors of ART use among alcohol
      drinkers. Using purposive sampling, we recruited 304 male and female patients
      from two ART clinics in Tshwane, South Africa. Interviews were conducted using a
      structured questionnaire comprising measures of demographic factors, psychosocial
      factors (i.e., ART adherence, self-efficacy beliefs, alcohol and ART interactions
      beliefs, ART-alcohol outcome expectancy, attitude towards drinking alcohol and
      taking ART and HIV stigma) and alcohol use (AUDIT). Data were analysed using
      descriptive statistics and three multivariate linear regressions. Forty percent
      of the sample reported drinking alcohol. Half of the drinkers endorsed one of
      three unique patterns of ART use: (1) dosing ART earlier than required (2) taking
      ART while drinking alcohol and (3) skipping ART doses. The other half endorsed
      combinations of ART use on drinking days, for example, earlier ART dosing and
      taking ART while drinking alcohol was the most common combination. High adherence
      perseverance (a self-efficacy subscale) and a non-favourable attitude towards
      drinking alcohol and taking ART predicted the unique pattern of taking ART early
      when planning to drink alcohol. The unique pattern of taking ART despite drinking
      alcohol was predicted by higher levels of education (marginal significance) and
      experiencing low HIV stigma. A high score on the AUDIT and experience of high
      stigma predicted the unique pattern of skipping ART doses when drinking alcohol.
      Patterns of ART taking in alcohol drinkers in this sample are varied, and not
      always mutually exclusive. This apparent complexity of medication taking patterns
      among alcohol drinkers warrants further exploration. Furthermore, the finding
      that different psychosocial factors predict different ART-taking patterns
      suggests a need for programmes to improve alcohol-related non-adherence to ART to
      be multifaceted. 

PMID- 24731109
TI  - Negative electrospray ionization via deprotonation: predicting the ionization
      efficiency.
AB  - Electrospray ionization (ESI) in the negative ion mode has received less
      attention in fundamental studies than the positive ion electrospray ionization.
      In this paper, we study the efficiency of negative ion formation in the ESI
      source via deprotonation of substituted phenols and benzoic acids and explore
      correlations of the obtained ionization efficiency values (logIE) with different
      molecular properties. It is observed that stronger acids (i.e., fully
      deprotonated in the droplets) yielding anions with highly delocalized charge
      [quantified by the weighted average positive sigma (WAPS) parameter rooted in the
      COSMO theory] have higher ionization efficiency and give higher signals in the
      negative-ion ESI/MS. A linear model was obtained, which equally well describes
      the logIE of both phenols and benzoic acids (R(2) = 0.83, S = 0.40 log units) and
      contains only an ionization degree in solution (alpha) and WAPS as molecular
      parameters. Both parameters can easily be calculated with the COSMO-RS method.
      The model was successfully validated using a test set of acids belonging neither
      to phenols nor to benzoic acids, thereby demonstrating its broad applicability
      and the universality of the above-described relationships between IE and
      molecular properties. 

PMID- 24731110
TI  - Selective synthesis of Cu2SnSe3 and Cu2SnSe4 nanocrystals.
AB  - The selective synthesis of Cu2SnSe3 and Cu2SnSe4 nanocrystals was achieved by a
      one-step solvothermal synthesis method. We also investigated the effects of
      different precursor sources and starting material concentrations on the phase
      purity of the products. Powder X-ray diffraction, elemental analysis, and
      magnetic susceptibility measurements were used to investigate the phase, purity,
      and homogeneity of the nanocrystals. This solvothermal approach is broadly
      applicable and may also be employed for the synthesis of other ternary or
      quaternary chalcogenide nanocrystals. 

PMID- 24731111
TI  - The comparative effectiveness of individual and group brief motivational
      interventions for mandated college students.
AB  - Individual brief motivational intervention (iBMI) is an efficacious strategy to
      reduce heavy drinking by students who are mandated to receive an alcohol
      intervention following an alcohol-related event. However, despite the strong
      empirical support for iBMI, it is unknown if the results from rigorously
      controlled research on iBMI translate to real-world settings. Furthermore, many
      colleges lack the resources to provide iBMI to mandated students. Therefore,
      group-delivered BMI (gBMI) might be a cost-effective alternative that can be
      delivered to a large number of individuals. The purpose of this study was to
      conduct a comparative effectiveness evaluation of iBMI and gBMI as delivered by
      staff at a university health services center. Participants (N = 278) were college
      students who were mandated to receive an alcohol intervention following an
      alcohol-related incident. Participants were randomized to receive an individual
      (iBMI; n = 133) or a Group BMI (gBMI; n = 145). Results indicated that both iBMI
      and gBMI participants reduced their peak estimated blood alcohol concentration
      (BAC) and the number of negative alcohol-related consequences at 1-, 3-, and 6
      months postintervention. The iBMI and gBMI conditions were not significantly
      different at follow-up. These findings provide preliminary support for the use of
      iBMI and gBMIs for college students in real-world settings.

PMID- 24731112
TI  - Does negative affect mediate the relationship between daily PTSD symptoms and
      daily alcohol involvement in female rape victims? Evidence from 14 days of
      interactive voice response assessment.
AB  - The negative reinforcement model of addiction posits that individuals may use
      alcohol to reduce negative affective (NA) distress. The current study
      investigated the mediating effect of daily NA on the relationship between daily
      PTSD symptoms and same-day and next-day alcohol involvement (consumption and
      desire to drink) in a sample of 54 non-treatment-seeking female rape victims who
      completed 14 days of interactive voice response assessment. The moderating effect
      of lifetime alcohol use disorder diagnosis (AUD) on daily relationships was also
      examined. Multilevel models suggested that NA mediated the relationship between
      PTSD and same-day, but not next-day alcohol involvement. NA was greater on days
      characterized by more severe PTSD symptoms, and alcohol consumption and desire to
      drink were greater on days characterized by higher NA. Furthermore, daily PTSD
      symptoms and NA were more strongly associated with same-day (but not next-day)
      alcohol consumption and desire to drink for women with an AUD than without.
      Results suggest that NA plays an important role in female rape victims' daily
      alcohol use. Differences between women with and without an AUD indicate the need
      for treatment matching to subtypes of female rape victims.

PMID- 24731113
TI  - Positive smoking outcome expectancies mediate the relation between alcohol
      consumption and smoking urge among women during a quit attempt.
AB  - Social learning models of addiction hypothesize that situational factors interact
      with cognitive determinants to influence a person's motivation to use substances.
      Ecological momentary assessment was used to examine the association between
      alcohol consumption, smoking outcome expectancies, and smoking urge during the
      first 7 days of a smoking quit attempt. Participants were 113 female smokers who
      enrolled in a study that tested an individually tailored smoking cessation
      treatment. Participants carried a palm-top personal computer for 7 days and were
      instructed to complete 4 random assessments each day and to initiate an
      assessment when they were tempted to smoke. Multilevel mediational analyses were
      used to examine (a) the effects of alcohol consumption before time j and positive
      smoking outcome expectancies at time j on smoking urge at time j + 1 (Model 1)
      and (b) the effects of alcohol consumption before time j and smoking urge at time
      j on positive smoking outcome expectancies at time j + 1 (Model 2). Model 1 found
      a significant effect of alcohol consumption before time j on smoking urge at time
      j + 1 (p = .04), and this effect was significantly mediated by positive smoking
      outcome expectancies at time j (p < .0001). Model 2 failed to find a significant
      effect of alcohol consumption before time j on positive smoking outcome
      expectancies at time j + 1. The findings suggest that alcohol consumption is
      significantly associated with increased positive smoking outcome expectancies
      that, in turn, are associated with increased smoking urge in women seeking to
      quit smoking.

PMID- 24731115
TI  - Associations of attention-deficit hyperactivity disorder symptom dimensions with
      smoking deprivation effects in adult smokers.
AB  - Identifying relations of attention deficit hyperactivity disorder (ADHD) symptom
      dimensions to individual facets of the tobacco withdrawal syndrome could
      elucidate the mechanisms linking ADHD and regular smoking. This study examined
      the unique relations of inattention (IN) and hyperactivity-impulsivity (HI)
      symptom dimensions of ADHD to a variety of tobacco withdrawal symptoms. One
      hundred thirty-two community-dwelling adult smokers recruited without regard to
      ADHD status completed a self-report measure of ADHD symptoms experienced over the
      past 6 months at a baseline visit. At two subsequent experimental sessions (one
      following overnight tobacco deprivation and one nondeprived; order
      counterbalanced), participants completed measures of tobacco withdrawal symptoms,
      mood, and desire to smoke. Preliminary analyses showed that higher levels of IN
      and HI symptoms were both associated with higher levels of negative affect and
      concentration difficulties during nondeprived ("baseline") states (ps < .01).
      Over and above nondeprived ratings, higher levels of HI symptoms were associated
      with larger deprivation-induced increases in negative affect, concentration
      problems, and desire to smoke, particularly for negative affect relief, during
      deprived states (ps < .01). ADHD symptoms, particularly HI symptoms, are
      associated with more severe exacerbations in abstinence-induced withdrawal
      symptoms, which could be an important mechanism of ADHD-smoking comorbidity.
      These findings suggest the need for clinical studies examining the role of these
      unique and potentially more severe withdrawal profiles experienced by smokers
      with high-levels of ADHD symptoms in smoking reinstatement and cessation
      outcomes.

PMID- 24731116
TI  - Alcohol affects video lottery terminal (VLT) gambling behaviors and cognitions
      differently.
AB  - People frequently combine alcohol use and gambling. However, our understanding of
      the effects of alcohol on gambling behavior is limited, both in terms of what the
      effects are and how they occur. The effects of a moderately intoxicating dose of
      alcohol (i.e., a blood alcohol concentration of .06 g%) on the video lottery
      terminal (VLT) gambling behaviors and cognitions of community-recruited
      nonpathological (n = 30) and probable pathological gamblers (n = 30) were
      compared. Alcohol increased the rate of double up betting (i.e., choosing to play
      a bonus game, after a winning video poker hand, which involves trying to pick a
      higher ranked card than the dealer's card from among 5 face down cards) of
      probable pathological gamblers, but did not influence their irrational beliefs
      about VLT play. Alcohol maintained the irrational beliefs about VLT play of
      nonpathological gamblers, but did not influence their gambling behaviors. Results
      are consistent with a growing body of research finding that gambling cognitions
      have an equivocal role in explaining actual gambling behaviors. Potential
      mechanisms for the observed effects are discussed. Applied implications discussed
      include: educating regular VLT players about the effects of alcohol on irrational
      gambling cognitions; reconsidering policies and practices that make alcohol
      available where machine gambling takes place; and targeting even moderate alcohol
      use in the treatment of gambling problems.

PMID- 24731118
TI  - A preliminary evaluation of a web-based intervention for college marijuana use.
AB  - Young adults in college have high rates of marijuana use, abuse, and dependence.
      Web-based interventions are increasingly popular, but their dissemination exceeds
      empirical support. One popular but understudied program is The Marijuana eCHECKUP
      TO GO (e-TOKE) for Universities & Colleges (San Diego State University Research
      Foundation, 2009). The aim of the present study was to evaluate its short-term
      effectiveness in changing marijuana involvement and perceived norms in
      undergraduates. Participants were 317 undergraduates (52% female, 78% White) who
      reported marijuana use within the month preceding baseline; each was randomly
      assigned to 1 of 4 conditions formed by crossing e-TOKE versus assessment only,
      with brief versus extensive baseline assessment (to assess assessment
      reactivity). Thus, 161 (51%) received eTOKE (77 with extended baseline, 84 with
      brief baseline), and 156 (49%) received assessment-only control (85 with extended
      baseline, 71 with brief baseline). 1 month later, all participants reported on
      marijuana use, problems, abuse and dependence symptoms, and norms. Assessment
      reactivity analyses yielded no significant differences by assessment condition.
      Individuals completing the e-TOKE program reported less extreme descriptive norms
      (ps < 0.01) but no decrease in marijuana use frequency, problems, abuse or
      dependence symptoms, or changes in injunctive norms (ps > 0.10). Thus, e-TOKE
      reduces perceptions of others' use, but this study did not provide evidence for
      its utility in changing personal use and problem indicators in the short-term.
      More research with longer follow-ups is indicated, given the possibility that
      descriptive norms could mediate behavior change.

PMID- 24731117
TI  - A longitudinal study of childhood ADHD and substance dependence disorders in
      early adulthood.
AB  - Attention deficit hyperactivity disorder (ADHD) is a childhood disorder that is
      associated with many behavioral and social problems. These problems may continue
      when an individual continues to meet criteria for ADHD as an adult. In this
      study, we describe the outcome patterns for three different groups: individuals
      who had ADHD as children, but no longer meet criteria as adults (Childhood
      Limited ADHD, n = 71); individuals who met ADHD criteria as children and continue
      to meet criteria as young adults (Persistent ADHD n = 79); and a control group of
      individuals who did not meet ADHD diagnostic criteria in childhood or adulthood
      (n = 69). Groups were compared with examine differences in change in rates of
      alcohol, marijuana, and nicotine dependence over 3 time points in young adulthood
      (mean ages 18, 20, and 22 years). The method used is notable as this longitudinal
      study followed participants from childhood into young adulthood instead of
      relying on retrospective self-reports from adult participants. Results indicated
      that there were no significant group differences in change in rates of substance
      dependence over time. However, individuals whose ADHD persisted into adulthood
      were significantly more likely to meet DSM-IV criteria for alcohol, marijuana,
      and nicotine dependence across the 3 time points after controlling for age, sex,
      childhood stimulant medication use, and childhood conduct problems. Implications
      of these findings, as well as recommendations for future research, are discussed.

PMID- 24731119
TI  - Treatment-seeking precipitators in problem gambling: analysis of data from a
      gambling helpline.
AB  - Although research on treatment precipitators for problem gambling is scarce,
      telephone surveys have consistently shown that financial and emotional problems
      resulting from problem gambling are the factors which recovered or active
      gamblers most frequently report as treatment precipitators. The present study
      sought to build on previous evidence by analyzing the demographic and gambling
      related information provided by gamblers calling the helpline operated by the New
      Mexico Council on Problem Gambling and receiving a referral to private
      counseling. Specifically we examined the differences between the callers who
      initiated treatment with a private counselor after receiving the referral (n =
      223), and those who were likewise referred to counseling but did not attend the
      first appointment (n = 231). The 2 groups could only be distinguished by the fact
      that the therapy-initiating group cited family or financial problems as the
      reason for calling the helpline. Further analyses revealed that helpline staff
      also had an influence on counseling initiation. These findings, along with other
      differences between groups call for further research on the most effective ways
      of targeting problem gamblers who call a helpline so as to facilitate their
      progression to the action stage of change.

PMID- 24731121
TI  - Serum paraoxonase-1 enzyme activities and oxidative stress levels in patients
      with esophageal squamous cell carcinoma.
AB  - OBJECTIVES: Oxidative stress is well recognized to play a role in the
      pathogenesis of many diseases, including cancers. Paraoxonase-1 (PON1) is
      implicated in the elimination of carcinogenic lipid-soluble radicals produced by
      lipid peroxidation. Reports on PON1 activities in patients with cancer are
      conflicting. The aim of this study was to investigate serum antioxidant enzyme
      activities and oxidative stress levels in patients with esophageal squamous cell
      carcinoma (ESCC). PATIENTS AND METHODS: Thirty-two patients with ESCC and 33
      healthy controls were enrolled. Serum malondialdehyde (MDA) levels and superoxide
      dismutase (SOD), glutathione peroxidase (GSH-Px), glutathione reductase (GR),
      paraoxonase, and arylesterase activities were measured spectrophotometrically.
      RESULTS: Serum paraoxonase, arylesterase, SOD, activities, GSH-Px, and GR
      activities were significantly lower in patients with ESCC than in controls (all,
      P < 0.05), whereas serum MDA levels were significantly higher (P < 0.05). Serum
      MDA levels were significantly correlated with paraoxonase (r = -0.572, P < 0.001)
      and arylesterase activities (r = -0.597, P < 0.001) in patients with ESCC.
      CONCLUSIONS: This study indicated that ESCC is associated with increased
      oxidative stress and decreased antioxidant enzyme activities. Decreased serum
      PON1 enzyme activities may play a role in the progression and/or development of
      ESCC. Further studies are required to clarify these results.

PMID- 24731120
TI  - Family check-up effects across diverse ethnic groups: reducing early-adolescence
      antisocial behavior by reducing family conflict.
AB  - Multicultural responsiveness and adaptation have been a recent area of emphasis
      in prevention and intervention science. The changing demographics of the United
      States demand the development of intervention strategies that are acceptable and
      effective for diverse cultural and ethnic groups. The Family Check-Up (FCU) was
      developed to be an intervention framework that is flexible and adaptive to
      diverse cultural groups (Dishion & Stormshak, 2007 ). We empirically evaluated
      the extent to which the intervention is effective for improving youth adjustment
      and parent-child interactions for diverse cultural groups. A sample of 1,193
      families was drawn from 2 large-scale randomized prevention trials conducted in
      diverse urban middle schools. We formulated 3 groups on the basis of youth self
      identification of ethnicity (European American, African American, Hispanic) and
      examined group differences in the hypothesized mediating effect of family
      conflict (FC) on later antisocial behavior (ASB). Path analysis revealed that
      youths in the intervention condition reported significantly less ASB over a 2
      year period (Grades 6-8). Moreover, youth-reported reductions in FC at 12 months
      were an intervening effect. Ethnicity did not moderate this relationship.
      Consistent with one of the primary tenets of coercion theory, participation in
      the FCU acts on ASB through FC across diverse ethnic groups, lending support to
      the multicultural competence of the model. Limitations of this study are
      discussed, along with areas for future research. 

PMID- 24731122
TI  - Preferential host switching and codivergence shaped radiation of bark beetle
      symbionts, nematodes of Micoletzkya (Nematoda: Diplogastridae).
AB  - Host-symbiont systems are of particular interest to evolutionary biology because
      they allow testable inferences of diversification processes while also providing
      both a historical basis and an ecological context for studies of adaptation. Our
      investigations of bark beetle symbionts, predatory nematodes of the genus
      Micoletzkya, have revealed remarkable diversity of the group along with a high
      level of host specificity. Cophylogenetic analyses suggest that evolution of the
      nematodes was largely influenced by the evolutionary history of beetles. The
      diversification of the symbionts, however, could not be attributed to parallel
      divergence alone; our results indicate that adaptive radiation of the nematodes
      was shaped by preferential host shifts among closely related beetles along with
      codivergence. Whereas ecological and geographic isolation have played a major
      role in the diversification of Micoletzkya at shallow phylogenetic depths,
      adaptations towards related hosts have played a role in shaping cophylogenetic
      structure at a larger evolutionary scale. 

PMID- 24731123
TI  - Commentary: ILAE Definition of Epilepsy.

PMID- 24731124
TI  - Two stable phosphorus-containing four-membered ring radical cations with inverse
      spin density distributions.
AB  - Two phosphorus-containing four-membered ring radical cations 1(*+) and 2(*+) have
      been isolated and characterized by UV-vis absorption spectroscopy, electron
      paramagnetic resonance (EPR), and single-crystal X-ray diffraction. Compared with
      neutral molecules 1 and 2, radical 1(*+) has elongated P-P bonds and more
      pyramidalized phosphorus atoms, while shortened P-Nring distances and larger
      angles around phosphorus centers are observed for 2(*+). EPR studies indicate
      that for 1(*+) spin density mainly resides on the exocyclic nitrogen atoms with
      very minor contribution from endocyclic phosphorus atoms, while the situation is
      opposite for 2(*+). Such an inverse spin density distribution is controlled by
      the exocyclic substituents, which is supported by DFT calculations. 

PMID- 24731125
TI  - Propensity-score matched analysis comparing robot-assisted with laparoscopic
      partial nephrectomy.
AB  - OBJECTIVES: To compare the peri-operative and early renal functional outcomes of
      robot-assisted partial nephrectomy (RAPN) and laparoscopic partial nephrectomy
      (LPN) for kidney tumours. MATERIALS AND METHODS: A total of 237 patients
      fulfilling the selection criteria were included, of whom 146 and 91 patients were
      treated with LPN and RAPN, respectively. To adjust for potential baseline
      confounders, propensity-score matching was performed. A favourable outcome was
      defined as a warm ischaemia time (WIT) of <=20 min, negative surgical margins, no
      surgical conversion, no Clavien >=3 complications and no postoperative chronic
      kidney disease (CKD) upstaging. Descriptive statistics and multivariable logistic
      regression analyses were performed before and after propensity-score matching.
      RESULTS: Within the propensity-score-matched cohort, the RAPN group was
      associated with significantly lower estimated blood loss (EBL; 156 vs 198 mL,
      mean difference [MD] = -42; P = 0.025), a shorter WIT (22.8 vs 31 min, MD = -8.2;
      P < 0.001) and a higher proportion of malignant lesions (88.4 vs 67.5%; odds
      ratio [OR]: 2.6; 95% confidence interval [CI]: 1.2-5.67; P = 0.023). With regard
      to early renal functional outcomes, the mean last estimated glomerular filtration
      rate was 95.8 and 89.4 mL/min per 1.73 m(2) (MD = 6.4; P = 0.01), with a mean +/-
      sd percentage change of -4.8 +/- 17.9 and -12.2 +/- 16.6 (MD = 7.4; P = 0.018) in
      the RAPN and LPN groups, respectively. The intra-operative complication rate was
      significantly lower in the RAPN group (1.3 vs 11.7%; OR 0.1, 95% CI 0.01-0.81; P
      = 0.018). On multivariable analysis, surgical approach (RAPN vs LPN, OR 5.457,
      95% CI 2.075-14.346; P = 0.001), Charlson Comorbidity Index (OR 0.223; 95% CI
      0.062-0.811; P = 0.023), diameter-axial-polar score (OR 0.488, 95% CI 0.329
      0.723; P < 0.001) and preoperative CKD stage (OR 3.189, 95% CI 1.204-8.446; P =
      0.020) were found to be independent predictors of obtaining a favourable outcome.
      CONCLUSIONS: After adjusting for potential treatment selection biases, RAPN was
      found to be superior to LPN for peri-operative outcomes (EBL, WIT and intra
      operative complications) and early renal functional preservation.

PMID- 24731126
TI  - An eye-tracking assistive device improves the quality of life for ALS patients
      and reduces the caregivers' burden.
AB  - Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease.
      In some cases, patients with ALS retain a normal level of consciousness but
      disease progression eventually results in generalized paralysis, which first
      impedes and then prevents oral communication. This communication obstacle can
      generate a great deal of stress for the patient, family, and caregiver. Here the
      authors ask whether the use of an eye-tracking assistive device can improve
      quality of life for ALS patients and relieves burden of their primary caregivers.
      Subjects were divided into two groups depending on whether they used (n = 10) or
      did not use (n = 10) an eye-tracking assistive device. The authors assessed
      patients' quality of life and severity of depression using the ALS Specific
      Quality of Life Instrument-Revised and the Taiwanese Depression Questionnaire,
      respectively. The Caregiver Burden Scale was used to assess the burden on
      caregivers. Our study shows that the eye-tracking assistive device significantly
      improved patients' quality of life, as compared with patients in the nonuser
      group (p <.01). The assistive device also reduced the burden on caregivers (p
      <.05). This is likely a result of the improvement of patient's autonomy and more
      effective communication between patient and caregiver.

PMID- 24731127
TI  - Assaying FVIII activity: one method is not enough, and never was.

PMID- 24731128
TI  - Matrix-assisted laser desorption/ionization (MALDI) imaging mass spectrometry
      (IMS): peering into the cup of Jamshid.
AB  - The complex process underlying the development of blood-induced joint disease
      remains mysterious. Novel technologies such as matrix-assisted laser
      desorption/ionization (MALDI) imaging mass spectrometry (IMS) to examine protein
      signatures may provide clues into the process. 

PMID- 24731129
TI  - Kreuth III: European consensus proposals for treatment of haemophilia with
      coagulation factor concentrates.
AB  - This report summarizes recommendations relating to haemophilia therapy arising
      from discussions among experts from 36 European countries during the Kreuth III
      meeting in April 2013. To optimize the organization of haemophilia care
      nationally, it is recommended that a formal body be established in each country
      to include the relevant clinicians, national haemophilia patient organization,
      health ministry, paying authority and (if appropriate) regulatory authorities.
      The minimum factor VIII consumption level in a country should be 3 I.U. per
      capita. Decisions on whether to adopt a new product should not be based solely on
      cost. Prophylaxis for children with severe haemophilia is already recognized as
      the optimum therapy. Ongoing prophylaxis for individual adults should also be
      provided when required based on clinical decision making by the clinician in
      consultation with the patient. Children with inhibitors who have failed, or who
      are not suitable for, immune tolerance therapy should be offered prophylaxis with
      bypassing agents. Single factor concentrates should be used as therapy wherever
      possible in patients with rare bleeding disorders. Orphan drug designation for a
      factor concentrate should not be used to hinder the development, licencing and
      marketing of other products for the same condition which have demonstrably
      different protein modification or enhancement. 

PMID- 24731130
TI  - High titre inhibitor to factor VIII in a haemophilia carrier.

PMID- 24731131
TI  - The effect of a specialized case management programme on the cost of factor
      replacement use in patients with bleeding disorders.

PMID- 24731133
TI  - Gold-decorated titania nanotube arrays as dual-functional platform for surface
      enhanced Raman spectroscopy and surface-assisted laser desorption/ionization mass
      spectrometry.
AB  - In this report, we demonstrate gold-decorated titania nanotube arrays (Au-TNA
      substrate) as a dual-functional platform for surface-enhanced Raman spectroscopy
      (SERS) and surface-assisted laser desorption/ionization mass spectrometry (SALDI
      MS). The Au nanoparticles are grown on the substrate using vapor deposition of
      Au. The resulting substrates perform better than Au colloids in terms of the
      reproducibility of the SERS measurements, long-term stability of the fabricated
      structures, and clean surface of the Au. The nanostructure of the Au-TNA
      substrate was designed to optimize the SALDI-MS and SERS performance. Excellent
      reproducibility of the SERS measurements using the Au-TNA substrate was obtained,
      with a standard error less than 6 %. SALDI activity was also demonstrated for the
      same Au-TNA substrates. Finally, the Au-TNA substrate was used for combined SERS
      and SALDI-MS analysis (i) to discriminate the structural isomers of pyridine
      compounds (para-, meta-, and ortho-pyridinecarboxylic acid) and (ii) to detect
      polycarbamate, a dithiocarbamate fungicide. These results are difficult to obtain
      using either approach alone.

PMID- 24731134
TI  - Multiple hydrogen-bonding interactions of uric acid/9-methyluric acid with
      melamine identified by infrared spectroscopy.
AB  - Hydrogen-bonded complexes of uric acid/9-methyluric acid (UA/9MUA) with melamine
      (MEL) are prepared by the combined technique of laser desorption and supersonic
      jet expansion, and their stable structures are investigated by infrared
      spectroscopy and theoretical calculations. It is shown that the 1:1 complex
      formed between UA and MEL is of nonplanar type, in which the two chromophore
      planes are significantly folded and thus allow for triple hydrogen-bonding
      interactions. An anomalously broad IR band is observed in the low-frequency range
      2500-2800 cm(-1), which is taken as evidence for the formation of a strong
      hydrogen bond between one of the NH sites of UA and MEL. In the case of 9MUA, in
      which hydrogen bonding to the N9H site of UA is blocked by the methyl group, two
      planar pairs formed of 9MUA and MEL are found to coexist. The nature of the
      multiple hydrogen-bonding interactions in these complexes is discussed based on
      the natural bond orbital analysis and compared with those of the guanine-cytosine
      base pair. The results are expected to provide important information on the
      structural characterization of urinary stones developed in infants after
      ingesting MEL-contaminated formula. 

PMID- 24731132
TI  - Therapeutic effects of pharmacologically induced hypothermia against traumatic
      brain injury in mice.
AB  - Preclinical and clinical studies have shown therapeutic potential of mild-to
      moderate hypothermia for treatments of stroke and traumatic brain injury (TBI).
      Physical cooling in humans, however, is usually slow, cumbersome, and
      necessitates sedation that prevents early application in clinical settings and
      causes several side effects. Our recent study showed that pharmacologically
      induced hypothermia (PIH) using a novel neurotensin receptor 1 (NTR1) agonist,
      HPI-201 (also known as ABS-201), is efficient and effective in inducing
      therapeutic hypothermia and protecting the brain from ischemic and hemorrhagic
      stroke in mice. The present investigation tested another second-generation NTR1
      agonist, HPI-363, for its hypothermic and protective effect against TBI. Adult
      male mice were subjected to controlled cortical impact (CCI) (velocity=3 m/sec,
      depth=1.0 mm, contact time=150 msec) to the exposed cortex. Intraperitoneal
      administration of HPI-363 (0.3 mg/kg) reduced body temperature by 3-5 degrees C
      within 30-60 min without triggering a shivering defensive reaction. An additional
      two injections sustained the hypothermic effect in conscious mice for up to 6 h.
      This PIH treatment was initiated 15, 60, or 120 min after the onset of TBI, and
      significantly reduced the contusion volume measured 3 days after TBI. HPI-363
      attenuated caspase-3 activation, Bax expression, and TUNEL-positive cells in the
      pericontusion region. In blood-brain barrier assessments, HPI-363 ameliorated
      extravasation of Evans blue dye and immunoglobulin G, attenuated the MMP-9
      expression, and decreased the number of microglia cells in the post-TBI brain.
      HPI-363 decreased the mRNA expression of tumor necrosis factor-alpha and
      interleukin-1beta (IL-1beta), but increased IL-6 and IL-10 levels. Compared with
      TBI control mice, HPI-363 treatments improved sensorimotor functional recovery
      after TBI. These findings suggest that the second generation NTR-1 agonists, such
      as HPI-363, are efficient hypothermic-inducing compounds that have a strong
      potential in the management of TBI.

PMID- 24731135
TI  - Inverse effects of midlife occupational and leisure time physical activity on
      mobility limitation in old age--a 28-year prospective follow-up study.
AB  - OBJECTIVES: To evaluate in a sample of initially middle-aged municipal employees
      whether leisure time (LPA) or occupational physical activity (OPA) was associated
      with mobility limitation (ML) in old age. DESIGN: Prospective population-based
      follow-up. SETTING: Municipalities in Finland. PARTICIPANTS: Public sector
      employees from the Finnish Longitudinal Study on Municipal Employees (FLAME)
      initially aged 44 to 58 (N = 5,200). MEASUREMENTS: Baseline data were collected
      in 1981, including LPA (average exercise within previous year: inactive (no
      exercise), moderate (some form of exercise <= 1 time per week), vigorous (brisk
      exercise >= 1 time per week)) and OPA (usual activities at work within previous
      year: light (light work sitting, standing, or moving around), moderate (moderate
      work moving around), vigorous (heavy physical work)). Number of MLs was assessed
      using a questionnaire (8 items) in 1985, 1992, 1997, and 2009; the latest
      mobility score available for each subject was used for analyses. Incidence rate
      ratios (IRRs) and 95% confidence intervals (CIs) for LPA and OPA predicting ML
      were estimated in a joint Poisson regression model adjusted for survival data;
      the other type of PA; and sociodemographic, socioeconomic, and health-related
      factors. RESULTS: Mean age at baseline was 50.3 +/- 3.6; 56.9% of participants
      were female. Participants with vigorous OPA in midlife had greater risk of a unit
      increase in ML in old age than those with light OPA (fully adjusted IRR = 1.09,
      95% CI = 1.03-1.16). Participants with vigorous LPA had lower risk of ML than
      inactive participants (fully adjusted IRR = 0.81, 95% CI = 0.76-0.86).
      CONCLUSION: Findings suggest that LPA and OPA in midlife have independent,
      inverse effects on mobility in old age in terms of a harmful effect of vigorous
      OPA and a protective effect of vigorous LPA.

PMID- 24731136
TI  - Natural tetraponerines: a general synthesis and antiproliferative activity.
AB  - A stereocontrolled general methodology to access all natural tetraponerines from
      (+)-T1 to (+)-T8 is detailed. Two consecutive indium-mediated aminoallylations
      with the appropriate enantiomer of chiral N-tert-butylsulfinamide and a
      thermodynamic control at the aminal stereocenter allow the formation of each
      natural tetraponerine with excellent stereoselectivity. The use of 4-bromobutanal
      in the first aminoallylation leads to the formation of 5-6-5 tetraponerines,
      while 5-bromopentanal is required to build the scaffold of 6-6-5 tetraponerines.
      A cross-metathesis reaction of the second aminoallylation product with cis-3
      hexene is used to elongate the side chain up to 5 carbons so as to prepare the
      tetraponerines T5 to T8. The anticancer activity of these heavier tetraponerines
      against four different carcinoma human cell lines is examined, observing a
      promising cytotoxic activity of (+)-T7 against breast carcinoma cell line MCF-7. 

PMID- 24731137
TI  - Direct synthesis of highly porous interconnected carbon nanosheets and their
      application as high-performance supercapacitors.
AB  - An easy, one-step procedure is proposed for the synthesis of highly porous carbon
      nanosheets with an excellent performance as supercapacitor electrodes. The
      procedure is based on the carbonization of an organic salt, i.e., potassium
      citrate, at a temperature in the 750-900  degrees C range. In this way, carbon
      particles made up of interconnected carbon nanosheets with a thickness of <80 nm
      are obtained. The porosity of the carbon nanosheets consists essentially of
      micropores distributed in two pore systems of 0.7-0.85 nm and 0.95-1.6 nm.
      Importantly, the micropore sizes of both systems can be enlarged by simply
      increasing the carbonization temperature. Furthermore, the carbon nanosheets
      possess BET surface areas in the ~1400-2200 m(2) g(-1) range and electronic
      conductivities in the range of 1.7-7.4 S cm(-1) (measured at 7.1 MPa). These
      materials behave as high-performance supercapacitor electrodes in organic
      electrolyte and exhibit an excellent power handling ability and a superb
      robustness over long-term cycling. Excellent results were obtained with the
      supercapacitor fabricated from the material synthesized at 850  degrees C in
      terms of both gravimetric and volumetric energy and power densities. This device
      was able to deliver ~13 Wh kg(-1) (5.2 Wh L(-1)) at an extremely high power
      density of 78 kW kg(-1) (31 kW L(-1)) and ~30 Wh kg(-1) (12 Wh L(-1)) at a power
      density of 13 kW kg(-1) (5.2 kW L(-1)) (voltage range of 2.7 V). 

PMID- 24731138
TI  - A two-step hierarchical hypothesis set testing framework, with applications to
      gene expression data on ordered categories.
AB  - BACKGROUND: In complex large-scale experiments, in addition to simultaneously
      considering a large number of features, multiple hypotheses are often being
      tested for each feature. This leads to a problem of multi-dimensional multiple
      testing. For example, in gene expression studies over ordered categories (such as
      time-course or dose-response experiments), interest is often in testing
      differential expression across several categories for each gene. In this paper,
      we consider a framework for testing multiple sets of hypothesis, which can be
      applied to a wide range of problems. RESULTS: We adopt the concept of the overall
      false discovery rate (OFDR) for controlling false discoveries on the hypothesis
      set level. Based on an existing procedure for identifying differentially
      expressed gene sets, we discuss a general two-step hierarchical hypothesis set
      testing procedure, which controls the overall false discovery rate under
      independence across hypothesis sets. In addition, we discuss the concept of the
      mixed-directional false discovery rate (mdFDR), and extend the general procedure
      to enable directional decisions for two-sided alternatives. We applied the
      framework to the case of microarray time-course/dose-response experiments, and
      proposed three procedures for testing differential expression and making multiple
      directional decisions for each gene. Simulation studies confirm the control of
      the OFDR and mdFDR by the proposed procedures under independence and positive
      correlations across genes. Simulation results also show that two of our new
      procedures achieve higher power than previous methods. Finally, the proposed
      methodology is applied to a microarray dose-response study, to identify 17 beta
      estradiol sensitive genes in breast cancer cells that are induced at low
      concentrations. CONCLUSIONS: The framework we discuss provides a platform for
      multiple testing procedures covering situations involving two (or potentially
      more) sources of multiplicity. The framework is easy to use and adaptable to
      various practical settings that frequently occur in large-scale experiments.
      Procedures generated from the framework are shown to maintain control of the OFDR
      and mdFDR, quantities that are especially relevant in the case of multiple
      hypothesis set testing. The procedures work well in both simulations and real
      datasets, and are shown to have better power than existing methods.

PMID- 24731139
TI  - Psychometric item analysis and validation of the Indonesian version of the
      Readiness for Interprofessional Learning Scale (RIPLS).
AB  - Complex health care needs in developing countries are stimulating development and
      implementation of interprofessional education (IPE). To better understand IPE, it
      is necessary to develop and evaluate an educational program that focuses on
      interprofessional learning (IPL) in Indonesia. However, no instrument in the
      Indonesian language has been developed to measure attitudes toward IPL. The aim
      of this study is to describe the process of a cross-cultural adaptation of the
      Readiness for Interprofessional Learning Scale (RIPLS) in an Indonesian version
      including determining its reliability and validity. The study was conducted among
      students enrolled in medical, nursing, pharmacy and public health courses at the
      State Islamic University, Jakarta, Indonesia, in 2012. The completed responses to
      RIPLS were collected from 755 students. The psychometric properties were analyzed
      by both exploratory factor analysis (EFA) and confirmatory factor analysis (CFA).
      EFA on 18-items revealed three factors accounting for 59.9% of the total
      variance. CFA resulted in a three-factor model over 16 items with satisfactory
      reliability (alpha coefficients >0.7), construct validity and acceptable indices
      of goodness of fit. We conclude that this Indonesian version of RIPLS with a
      three-factor model over 16 items is a valid tool to measure students' attitudes
      toward IPL.

PMID- 24731140
TI  - Motor-based autonomous microsensor for motion and counting immunoassay of cancer
      biomarker.
AB  - A motor-based autonomous microsensor is proposed for in situ visualization
      immunoassay of cancer biomarkers through motion readout or tag counting. The
      microsensor is prepared by functionalizing a newly designed gold-nanoparticle
      modified self-propelled polyaniline/Pt (AuNP/PANI/Pt) micromotor with capture
      antibody. The autonomous movement of the microsensor in the fuel-enhanced sample
      mixture results in the fast and selective recognition of the protein target and
      subsequent loading of the secondary-antibody-modified glycidyl methacrylate
      microspheres (GMA), which slows down the movement of the sensing microengine. The
      velocity of the microsensor and the number of GMA conjugated on the microsensor
      can be conveniently visualized using optical microscopy. They are negatively and
      positively correlated with the target concentration, respectively. Therefore, the
      microsensor can conveniently distinguish the concentration of carcinoembryonic
      antigen in a range of 1-1000 ng/mL. The motor-based microsensor can be easily
      prepared in batch using AuNP/PANI/Pt. The whole detection procedure for protein
      target can be completed in 5 min without any washing and separation step. This
      method shows considerable promise for diverse clinical and diagnostic
      applications. 

PMID- 24731141
TI  - Electric-field-driven alignment of chiral conductive polymer thin films.
AB  - We investigated the effect of an electric field on the alignment and structural
      properties of thin films of a chiral polybithiophene-based conductive polymer,
      functionalized with a protected l-cysteine amino acid. Thin films were obtained
      by exploiting both drop-casting and spin-coating procedures. The electric
      properties, the polarized Raman spectrum, the UV-vis spectrum, and the CD spectra
      were measured as a function of the electric field intensity applied during film
      formation. It was found that beyond the enhancement of the conductivity observed
      when the electric field aligns the polymer, the electric field significantly
      affects the chiral properties and the effect depends on the method of deposition.

PMID- 24731142
TI  - Detection, quantifications, and pharmacokinetics of ponazuril in healthy swine.
AB  - A study on pharmacokinetics of ponazuril in piglets was conducted after a single
      oral dose of 5.0 mg/kg b.w. Plasma concentrations were measured by high
      performance liquid chromatography assay with UV detector at 255-nm wavelength.
      Pharmacokinetic parameters were derived by use of a standard noncompartmental
      pharmacokinetic analysis. Samples from six piglets showed good plasma
      concentrations of ponazuril, which peaked at 5.83 +/- 0.94 MUg/mL. Mean +/- SD
      area under the plasma concentration-time curve was 1383.42 +/- 363.26 h/MUg/mL,
      and the elimination half-life was 135.28 +/- 19.03 h. Plasma concentration of
      ponazuril peaked at 42 h (range, 36-48 h) after administration and gradually
      decreased but remained detectable for up to 33 days. No adverse effects were
      observed during the study period. The results indicate that ponazuril was
      relatively well absorbed following a single dose, which makes ponazuril likely to
      be effective in swine. 

PMID- 24731143
TI  - Trust and the duty of organ donation.
AB  - Several recent publications in biomedical ethics argue that organ donation is
      generally morally obligatory and failure to do so is morally indefensible.
      Arguments for this moral conclusion tend to be of two kinds: arguments from
      fairness and arguments from easy rescue. While I agree that many of us have a
      duty to donate, in this article I criticize these arguments for a general duty of
      organ donation and their application to organ procurement policy. My concern is
      that these arguments neglect the role that trust plays in contemporary organ
      transplant policies and in differential rational attitudes toward donation.
      Recognizing donation as an achievement of trust, and acknowledging the warrant of
      many people's rational distrust or withheld trust in medicine, I argue, should
      have significant implications for the ethics of organ procurement. 

PMID- 24731144
TI  - Incidence and molecular characterization of hepatitis A viruses in Korean surface
      water between 2007 and 2010.
AB  - Several bodies of surface water in Korea were surveyed for the presence of
      hepatitis A virus (HAV) between 2007 and 2010. Of 265 surface water samples, 9
      (3.4%) were HAV-positive. HAVs were mainly detected in the summer (3/62, 4.8%)
      and spring (4/96, 4.2%) seasons. Comparing different water sources, the highest
      prevalence (6.6%) of positive samples was seen in lake water, four HAV-positive
      samples being from lakes. Comparing prevalence rates across the four
      representative Korean basin systems, no HAVs were found in the Han or Nakdong
      river basins. The highest HAV prevalence was found in samples from the Yeongsan
      river and other basins (6.3%); the Geum/Seom river was also found to have a high
      HAV prevalence (5.7%). HAVs from the nine positive samples were then sequenced
      and analyzed phylogenetically. Two of the HAVs belong to genotype IA and fall
      within the same cluster as HAVs 6-3(ASAN4) (EU049548), KANSAN-PS1 (EU049554), and
      ASAN-KM (EU049563), which were collected from the stools of patients with
      gastroenteritis in Korea. The seven other HAV nucleotide sequences belong to the
      genotype IB cluster. This is the first nationwide surveillance of HAV in major
      Korean water sources. 

PMID- 24731145
TI  - Misclassification and identification of emotional facial expressions in depressed
      youth: a preliminary study.
AB  - Accurate processing of social and affective cues, especially facial cues, is
      important for human adaptation. Previous studies have examined depressed adults'
      sensitivity to identify emotional facial expressions, yet only one study has
      investigated this in depressed youth. In addition, very little is known about
      whether depressed individuals exhibit biases when incorrectly labeling, or
      misclassifying, emotional expressions. Therefore, this preliminary study explored
      whether sensitivity to, or misclassification of, emotional facial expressions
      differed among currently depressed youth, those with a history of depression, and
      never-depressed control participants. A community sample of 280 youth (7-16
      years; M = 11.51, SD = 2.44; 56% girls) completed a forced-choice emotion
      identification task consisting of a series of randomly presented facial images
      that morphed an emotional expression (angry, happy, and sad) with a neutral
      expression in 10% increments (e.g., 10% sad/90% neutral; 20% sad/80% neutral).
      Findings demonstrated that currently depressed were more likely than remitted and
      never-depressed youth to misclassify happy and sad facial expressions as angry.
      No depression group differences were found in sensitivity to identify emotional
      expressions. Results suggest that currently depressed youth show biased
      perceptions of threat, which may contribute to the maintenance of their
      depressive symptoms.

PMID- 24731146
TI  - Obstructive sleep apnea and atrial fibrillation: understanding the connection.
AB  - There is a high incidence of atrial fibrillation (AF) in patients with
      obstructive sleep apnea (OSA). Whether this represents a causative relationship
      or is merely an association remains to be determined. This review describes the
      current understanding of pathophysiologic links supporting a causative
      relationship between OSA and AF. The management of AF with antiarrhythmics,
      cardioversion and ablation success depends on compliance with OSA treatment. OSA
      worsens every risk factor resulting in a higher stroke risk in AF patients.
      Strategies for early screening and compliance with OSA treatment are the need of
      the hour. 

PMID- 24731147
TI  - Frequency and correlates of late presentation for HIV infection in France: older
      adults are a risk group - results from the ANRS-VESPA2 Study, France.
AB  - Correlates of late presentation (LP) for HIV infection in Metropolitan France and
      French overseas departments (FODs) were assessed among HIV-infected patients
      recently diagnosed, using data from a large cross-sectional survey,
      representative of the French HIV-infected population, conducted in 2011. LP was
      defined as presentation with either clinical AIDS events within the calendar year
      of diagnosis or CD4 < 350/mm(3) and presentation with advanced disease (PAD) was
      defined as presentation with either clinical AIDS events or CD4 < 200/mm(3).
      Correlates of LP/PAD were assessed through logistic modelling, separately in
      Metropolitan France and FODs. In Metropolitan France, 47.7% of participants were
      late presenters and 29.3% presented with advanced disease. LP was more frequent
      among male and female migrants from sub-Saharan Africa (SSA; 58.5% and 56.4%) and
      non-African heterosexual males (61.8%) than among men who have sex with men
      (34.8%). In FODs, 53.2% of participants were late presenters and 36.8% presented
      with an advanced disease. LP was more frequent among men than women (60.6% vs.
      45.3%) and among those with a lower level of education (56.6% vs. 47.5%). A
      consistent positive association was found in adjusted analyses between LP/PAD and
      increasing age at diagnosis among all subpopulations, in both settings. In
      Metropolitan France, among men who have sex with men, those self-declaring as
      bisexual were at higher risk of LP/PAD; among non-African heterosexual males and
      females, religiosity was associated with increased risk of LP/PAD; and among SSA
      migrants, those diagnosed within the year following their arrival in France were
      at higher risk of LP/PAD. Older age at diagnosis is a major risk factor for
      LP/PAD independently of any other socio-demographic characteristics. Promotion of
      HIV testing should be renewed to target each subgroup at risk while paying a
      particular attention to middle-aged or older adults whose attitudes and beliefs
      towards HIV/AIDS might prevent them from seeking testing. 

PMID- 24731148
TI  - BK virus encoded microRNAs are present in blood of renal transplant recipients
      with BK viral nephropathy.
AB  - BK viral infection is an important cause of renal transplant dysfunction and
      failure. Current strategies utilize surveillance for infection with DNA
      polymerase chain reaction assays and modulation of immunosuppression. Many
      viruses including polyomaviruses encode microRNAs (miRNAs). We have detected BK
      virus (BKV) encoded miRNAs in the blood of infected renal transplant recipients,
      and see a strong correlation between BKV encoded miRNA and BKV DNA in blood and a
      relationship between levels of bkv-miR-B1-5p and the presence of biopsy-proven BK
      viral nephropathy. Further research is needed to determine whether the detection
      of this and other virally encoded miRNAs may be useful in the diagnosis of active
      viral replication. 

PMID- 24731149
TI  - Contrasting patterns of selection on the size and coloration of a female plumage
      ornament in common yellowthroats.
AB  - Females often possess ornaments that appear smaller and duller than homologous
      traits in males. These ornaments may arise as nonfunctional by-products of sexual
      selection in males and cause negative viability or fecundity selection in females
      in proportion to the cost of their production and maintenance. Alternatively,
      female ornaments may function as signals of quality that are maintained by sexual
      or social selection. In a 4-year study of 83 female common yellowthroats
      (Geothlypis trichas) and their 222 young, we found strong viability and fecundity
      selection on the yellow bib, a carotenoid-based plumage ornament that is a target
      of sexual selection in males. Females with larger bibs were older, larger and
      more fecund than females with smaller bibs. However, bib size positively covaried
      with bib total brightness and carotenoid chroma, aspects of bib coloration that
      were under negative viability and fecundity selection. Females with more
      colourful bibs laid fewer eggs in their first clutch, were more likely to suffer
      total brood loss due to predation and were less likely to return to the study
      area. Selection against bib coloration limits the value of bib size as a quality
      indicator in females and may constrain the elaboration of bib attributes in
      males. 

PMID- 24731150
TI  - From the editors: names count--the new operational definition of epilepsy and
      Epilepsia's poll.

PMID- 24731151
TI  - Photomanipulation of vasodilation with a blue-light-controllable nitric oxide
      releaser.
AB  - Spatiotemporally controllable nitric oxide (NO)-releasers allow us to analyze the
      physiological effects of NO, a gaseous mediator that modulates many biological
      signaling networks, and are also candidate chemotherapeutic agents. We designed
      and synthesized a blue-light-controllable NO releaser, named NOBL-1, which bears
      an N-nitrosoaminophenol moiety for NO release tethered to a BODIPY dye moiety for
      harvesting blue light. Photoinduced electron transfer from N-nitrosoaniline to
      the antenna moiety upon irradiation with relatively noncytotoxic blue light (470
      500 nm) should result in NO release with formation of a stable quinone moiety. NO
      release from NOBL-1 was confirmed by ESR spin trapping and fluorescence
      detection. Spatially controlled NO release in cells was observed with DAR-4M AM,
      a fluorogenic NO probe. We also demonstrated temporally controlled vasodilation
      of rat aorta ex vivo by blue-light-induced NO release from NOBL-1. This compound
      should be useful for precise examination of the functions of NO with excellent
      spatiotemporal control. 

PMID- 24731152
TI  - High-concentration Na doping of SrRuO3 and CaRuO3.
AB  - The Na-doped perovskite-structure ruthenates Sr(1-x)Na(x)RuO3 and Ca(1
      y)Na(y)RuO3 were prepared by high-pressure synthesis, which enables us to go
      beyond the previously reported Na doping limits and substitute Na for over 50% of
      the Sr in SrRuO3 and the Ca in CaRuO3. Gradual and systematic changes in the
      crystal structures were observed, and the decreases in the Ru-O bond lengths
      confirmed the Na substitution at the A site caused hole doping to Ru(4+) at the B
      site. In contrast to what has been previously reported, Sr(1-x)Na(x)RuO3 showed
      metallic conductivity. Magnetic properties were influenced by the Na
      substitution, but no long-range antiferromagnetic behavior was observed in Ca(1
      y)Na(y)RuO3.

PMID- 24731153
TI  - Serum ferritin as a new prognostic factor in hepatocellular carcinoma patients
      treated with radiofrequency ablation.
AB  - BACKGROUND AND AIM: Hepatic iron accumulation is considered to be a cofactor that
      influences liver injury and hepatocarcinogenesis. Aim of this study is to
      determine whether serum ferritin (SF) levels relate to overall survival (OS) and
      time to recurrence (TTR) in hepatocellular carcinoma (HCC) patients treated with
      percutaneous radiofrequency ablation (RFA). METHODS: We measured SF levels in 103
      HCC patients (median age 70, M/F = 82.5%/17.5%) who underwent RFA between 2005
      and 2010. Correlation between SF and other prognostic factors at baseline was
      analyzed. SF levels were entered into a Cox model and their influence on OS and
      TTR was evaluated in univariate and multivariate analyses. RESULTS: SF did not
      correlate with alpha-fetoprotein (rho: -0.12, P = 0.22), neutrophil/lymphocyte
      ratio (rho: -0.1020, P = 0.30), Model for End-Stage Liver Disease (rho: 0.18, P =
      0.06), Child-Pugh score (P = 0.5), or Barcelona Cancer of the Liver Clinic stage
      (P = 0.16). A log-rank test found the value of 244 ng/mL as the optimal
      prognostic cut-off point for SF. Median OS was 62 months (54-78) and survival
      rate was 97%, 65%, and 52% at 1, 4, and 5 years, respectively. Performance status
      and SF were the only predictors of OS at multivariate analysis. Median TTR was 38
      months (34-49) with a recurrence-free survival rate of 82.5%, 26.2%, and 23.3% at
      1, 4, and 5 years, respectively, while SF and age were the only predictors of
      TTR. CONCLUSIONS: SF level, possibly reflecting the degree of hepatic
      inflammation and fibrosis, is a negative risk factor for survival and recurrence
      after percutaneous RFA in HCC patients.

PMID- 24731154
TI  - Heart rate and perceived muscle pain responses to a functional walking test in
      McArdle disease.
AB  - The aim of this study was to assess a 12-min self-paced walking test in patients
      with McArdle disease. Twenty patients (44.7 +/- 11 years; 11 female) performed
      the walking test where walking speed, distance walked, heart rate (HR) and
      perceived muscle pain (Borg CR10 scale) were measured. Median (interquartile
      range) distance walked was 890 m (470-935). From 1 to 6 min, median walking speed
      decreased (from 75.0 to 71.4 m?min(-1)) while muscle pain and %HR reserve
      increased (from 0.3 to 3.0 and 37% to 48%, respectively). From 7 to 12 min,
      walking speed increased to 74.2 m?min(-1), muscle pain decreased to 1.6 and %HR
      reserve remained between 45% and 48%. To make relative comparisons, HR and muscle
      pain were divided by walking speed and expressed as ratios. These ratios rose
      significantly between 1 and 6 min (HR:walking speed P = .001 and pain:walking
      speed P < .001) and similarly decreased between 6 and 11 min (P = .002 and P =
      .001, respectively). Peak ratios of HR:walking speed and pain:walking speed were
      inversely correlated to distance walked: rs (HR) = -.82 (P < .0001) and rs (pain)
      = -.55 (P = .012). Largest peak ratios were found in patients who walked < 650 m.
      A 12-min walking test can be used to assess exercise capacity and detect the
      second wind in McArdle disease.

PMID- 24731155
TI  - Evaluating the performance of copula models in phase I-II clinical trials under
      model misspecification.
AB  - BACKGROUND: Traditionally, phase I oncology trials are designed to determine the
      maximum tolerated dose (MTD), defined as the highest dose with an acceptable
      probability of dose limiting toxicities(DLT), of a new treatment via a dose
      escalation study. An alternate approach is to jointly model toxicity and efficacy
      and allow dose escalation to depend on a pre-specified efficacy/toxicity tradeoff
      in a phase I-II design. Several phase I-II trial designs have been discussed in
      the literature; while these model-based designs are attractive in their
      performance, they are potentially vulnerable to model misspecification. METHODS:
      Phase I-II designs often rely on copula models to specify the joint distribution
      of toxicity and efficacy, which include an additional correlation parameter that
      can be difficult to estimate. We compare and contrast three models for the joint
      probability of toxicity and efficacy, including two copula models that have been
      proposed for use in phase I-II clinical trials and a simple model that assumes
      the two outcomes are independent. We evaluate the performance of the various
      models through simulation both when the models are correct and under model
      misspecification. RESULTS: Both models exhibited similar performance, as measured
      by the probability of correctly identifying the optimal dose and the number of
      subjects treated at the optimal dose, regardless of whether the data were
      generated from the correct or incorrect copula, even when there is substantial
      correlation between the two outcomes. Similar results were observed for a simple
      model that assumes independence, even in the presence of strong correlation.
      Further simulation results indicate that estimating the correlation parameter in
      copula models is difficult with the sample sizes used in Phase I-II clinical
      trials. CONCLUSIONS: Our simulation results indicate that the operating
      characteristics of phase I-II clinical trials are robust to misspecification of
      the copula model but that a simple model that assumes independence performs just
      as well due to difficulty in estimating the copula model correlation parameters
      from binary data.

PMID- 24731156
TI  - Low iodine diet for one week is sufficient for adequate preparation of high dose
      radioactive iodine ablation therapy of differentiated thyroid cancer patients in
      iodine-rich areas.
AB  - BACKGROUND: Most current guidelines suggest one or two weeks of low iodine diet
      (LID) before radioactive iodine ablation therapy (RAIT) to increase its efficacy
      in differentiated thyroid cancer (DTC) patients after total thyroidectomy. LID
      duration is particularly important for patients living in iodine excess areas.
      However, there is no standardized LID protocol and there are limited reports
      regarding the relationship between LID and ablation outcome. Therefore, we aimed
      to evaluate the optimal LID duration and define clinical features that affect
      ablation outcome. METHODS: A total of 202 papillary thyroid cancer patients with
      total thyroidectomy preparing for RAIT were enrolled. All patients had undergone
      two weeks of LID before (131)I administration. Morning spot urine specimens were
      obtained twice (one week or two weeks after LID, respectively) from each patient.
      Urine iodine excretion (UIE) values were used to evaluate LID efficacy.
      Successful ablation was defined using two definitions: (i) no visible uptake on a
      follow-up diagnostic (131)I scans, and (ii) no visible uptake on a follow-up
      diagnostic (131)I scans and stimulated serum thyroglobulin (Tg) levels <1 ng/mL.
      RESULTS: The UIE median values after LID for one and two weeks were lower than 50
      MUg/L, and the median UIE values were not significantly different according to
      the LID duration. Based on the first criterion for successful ablation, 175 of
      the 195 patients were successfully ablated. There were no significant differences
      in mean and median UIE levels between the ablated and non-ablated groups after
      LID for two weeks. The rate of ablation did not differ between the mild and
      moderate iodine deficient groups. Based on the second criterion for successful
      ablation, 149 of 188 patients were successfully ablated. The ablation success
      rate did not differ between UIE levels. When we analyzed clinical factors that
      affect ablation outcome, serum Tg level at the time of ablation was the only
      significant variable in multivariate logistic analysis. CONCLUSION: Strict LID
      for one week was sufficient to achieve target UIE values for RAIT preparation,
      even in iodine-rich areas.

PMID- 24731157
TI  - Development and internal validation of a nomogram for predicting stone-free
      status after flexible ureteroscopy for renal stones.
AB  - OBJECTIVE: To develop and internally validate a preoperative nomogram for
      predicting stone-free status (SF) after flexible ureteroscopy (fURS) for renal
      stones, as there is a need to predict the outcome of fURS for the treatment of
      renal stone disease. PATIENTS AND METHODS: We retrospectively analysed 310 fURS
      procedures for renal stone removal performed between December 2009 and April
      2013. Final outcome of fURS was determined by computed tomography 3 months after
      the last fURS session. Assessed preoperative factors included stone volume and
      number, age, sex, presence of hydronephrosis and lower pole calculi, and ureteric
      stent placement. Multivariate logistic regression analysis with backward
      selection was used to model the relationship between preoperative factors and SF
      after fURS. Bootstrapping was used to internally validate the nomogram. RESULTS:
      Five independent predictors of SF after fURS were identified: stone volume (P <
      0.001), presence of lower pole calculi (P = 0.001), operator with experience of
      >50 fURS (P = 0.026), stone number (P = 0.075), and presence of hydronephrosis (P
      = 0.047). We developed a nomogram to predict SF after fURS using these five
      preoperative characteristics. Total nomogram score (maximum 25) was derived from
      summing individual scores of each predictive variable; a high total score was
      predictive of successful fURS outcome, whereas a low total score was predictive
      of unsuccessful outcome. The area under the receiver operating characteristics
      for nomogram predictions was 0.87. CONCLUSION: The nomogram can be used to
      reliably predict SF based on patient characteristics after fURS treatment of
      renal stone disease.

PMID- 24731160
TI  - Morphological differences between imperative and declarative pointing: hand
      shape, arm extension, and body posture.
AB  - The authors used frame-by-frame video analyses to describe the features of
      imperative and declarative pointing gestures produced by young children, in
      comparison to reaching actions. First, the results showed that imperative
      pointing shared common features with reaching actions (hand shape, arm
      extension), but body posture observed in reaching differed from the one observed
      in pointing, both in imperative and declarative contexts. Second, hand shape was
      influenced by precision constraints: imperative gestures shifted from whole-hand
      pointing to index-finger pointing when the target was surrounded by distractors.
      This study is the first of its kind to highlight the effect of several variables
      on morphological features of pointing using quantitative measures and may provide
      insights into the nature of imperative and declarative pointing.

PMID- 24731159
TI  - A history of depressed skull fractures from ancient times to 1800.
AB  - The story of managing depressed fractures illustrates how knowledge of proven
      value does not always get handed down. Celsus was the first to describe sensible
      management for depressed fractures. As he wrote in Latin this was forgotten.
      Galen's Greek writings survived forming the basis of management until the
      sixteenth century. In 1517, Hans von Gersdorff published a formidable illustrated
      surgical text. One illustration depicts an instrument for elevating depressed
      bone fragments. It looked dramatic but could not work and its defects were
      finally defined in the eighteenth century. Ambroise Pare used a bone punch just
      as we do today, but no later surgeon mentions this, though the instrument was
      well known. Elements of chance, fashion, emotionally powerful illustrations, and
      perhaps stubbornness had a profound effect on management delaying rational
      treatment for centuries. 

PMID- 24731161
TI  - Monitoring intraocular pressure changes after intravitreal Ranibizumab injection
      using rebound tonometry.
AB  - PURPOSE: Direct drug delivery by intravitreal injection is an essential tool in
      the treatment of retinal diseases and can trigger transient and intermediate
      intraocular pressure (IOP) peaks. So far no reliable risk factors for pronounced
      IOP increments have been outlined, which might be particularly important for
      patients with increased IOP susceptibility such as glaucoma. In this prospective,
      interventional study IOP changes were analysed directly before and after
      injection in sitting and supine positions using the Icare rebound tonometer (RT).
      METHODS: The IOP of 29 patients with macular oedema, who underwent intravitreal
      injection of 0.05 mL Ranibizumab, was measured in a sitting position 5 min before
      and two, five and 10 min after surgery. In addition, IOP was also acquired 30 s
      before and 10 s after injection in a supine position. The effect of age, gender,
      pseudophakia, axial length, anterior chamber depth, central corneal thickness,
      scleral thickness and iridocorneal angle width was analysed. RESULTS: Mean pre
      injection IOP sitting was 14.3 +/- 2.6 mmHg for the treated and 15.5 +/- 2.2 mmHg
      for the control eye. After injection mean IOP rose to 47.2 +/- 11.2 mmHg on the
      treated eye. The IOP of 17 patients returned to values <=21 mmHg within 10 min.
      In 12 patients, IOP remained above 21 mmHg after 10 min. No specific risk factor
      for this group was found. The absolute IOP increase 10 s after injection was
      significantly correlated to scleral thickness (r = 0.49, p = 0.036) and to the
      absolute (r = 0.40, p = 0.03) and relative increase (r = 0.39, p = 0.035) of IOP
      from sitting 5 min before injection to supine position 10 s before injection.
      CONCLUSIONS: Posture change related IOP increments might have a predictive value
      for post injection IOP increase. In 40% of the eyes higher IOP-levels (>21 mmHg)
      remained persistent for a longer period of time. This should be considered
      especially for glaucomatous eyes.

PMID- 24731162
TI  - Efficacy and safety of splenectomy in telaprevir-based triple therapy for chronic
      hepatitis C patients with thrombocytopenia and advanced fibrosis.
AB  - BACKGROUND AND AIM: Thrombocytopenia (TCP) of chronic hepatitis C patients with
      cirrhosis has a negative impact on the management of interferon-based treatment.
      The aim of this study is to evaluate the efficacy and safety of telaprevir-based
      triple therapy for patients who have undergone splenectomy (Spx). METHODS: This
      prospective, multicenter study consisted of 80 patients, including 32 Spx and 48
      non-Spx/TCP (platelet count: 60-99 * 10(9) /L) patients with advanced fibrosis
      infected with hepatitis C virus genotype 1b. All received 12 weeks of telaprevir
      in combination with 24 weeks of pegylated interferon (PEG-IFN) alpha2b and
      ribavirin. RESULTS: The sustained virological response (SVR) rate of the Spx
      group (75.0%) was significantly higher than that of the non-Spx/TCP group (52.1%)
      (P < 0.05). Under favorable conditions such as treatment-naive/prior relapse and
      interleukin-28B (IL28B) TT allele (rs8099917), the SVR rates of the Spx group
      were significantly higher than those of the non-Spx/moderate TCP (60-79 * 10(9)
      /L) groups (91.3% vs 50.0% and 93.8% vs 37.5%, respectively; both P < 0.05).
      Adequate PEG-IFNalpha2b adherence was associated with SVR. However, the
      percentage of patients who achieved 80% adherence to PEG-IFNalpha2b in the non
      Spx/moderate TCP (42.9%) group was significantly lower than that of the Spx
      (79.3%) and non-Spx/mild TCP (80-99 * 10(9) /L) (80.0%) groups. Treatment
      discontinuation due to adverse effects and the development of bacterial infection
      did not differ between the Spx and non-Spx/TCP groups. CONCLUSION: The increase
      of platelet count after Spx contributed to treatment success, especially for
      moderate to severe TCP patients who are treatment-naive/prior relapse or IL28B TT
      allele.

PMID- 24731163
TI  - Plasma disposition kinetics of moxidectin after subcutaneous administration to
      pregnant sheep.
AB  - The plasma kinetic profile of moxidectin (MXD) in ewes during the last third of
      pregnancy was studied after the subcutaneous dose of 0.2 mg/kg of body weight
      (bw). Two groups of sheep (n = 7) that were equally balanced in body weight were
      used. Group I (control) was maintained unmated, while Group II (pregnant) was
      estrous-synchronized and mated with fertile rams. Both groups were maintained
      under similar conditions regarding management and feeding. When the ewes from
      Group II fulfilled 120 days of pregnancy, both groups were treated with a
      subcutaneous injection of 0.2 mg of MXD/kg bw. Blood samples were collected at
      different set times between 1 h and 40 days post-treatment. After plasma
      extraction and derivatization, the samples were analyzed using high-performance
      liquid chromatography with fluorescence detection. A noncompartmental
      pharmacokinetic analysis was performed, and the data were compared using
      Student's t-test. The mean pharmacokinetic parameters, including Cmax , Tmax ,
      and the area under the concentration-time curve (AUC), were similar for both
      groups of sheep. The average of elimination half-life was significantly lower (P
      = 0.0023) in the pregnant (11.49 +/- 2.2 days) vs. the control (17.89 +/- 4.84
      days) sheep. Similarly, the mean residence time (MRT) for the pregnant group
      (20.6 +/- 3.8 days) was lower (P = 0.037) than that observed in the control group
      (27.4 +/- 9.1 days). It is concluded that pregnancy produces a significant
      decrease in mean values of half-life of elimination of MXD, indicating that
      pregnancy can increase the rate of elimination of the drug reducing their
      permanence in the body. 

PMID- 24731166
TI  - High-performance photoconductivity and electrical transport of ZnO/ZnS core/shell
      nanowires for multifunctional nanodevice applications.
AB  - We report the electrical and optical properties of ZnO/ZnS core/shell nanowire
      (NW) devices. The spatial separation of charge carriers due to their type II band
      structure together with passivation effect on ZnO/ZnS core/shell NWs not only
      enhanced their charge carrier transport characteristics by confining the
      electrons and reducing surface states in the ZnO channel but also increased the
      photocurrent under ultraviolet (UV) illumination by reducing the recombination
      probability of the photogenerated charge carriers. Here the efficacy of the type
      II band structure and the passivation effect are demonstrated by showing the
      enhanced subthreshold swing (150 mV/decade) and mobility (17.2 cm2/(Vs)) of the
      electrical properties, as well as the high responsivity (4.4*10(6) A/W) in the
      optical properties of the ZnO/ZnS core/shell NWs, compared with the subthreshold
      swing (464 mV/decade), mobility (8.9 cm2/(Vs)) and responsivity (2.5*10(6) A/W)
      of ZnO NWs.

PMID- 24731164
TI  - Antibiotic exposure in pregnancy and risk of coeliac disease in offspring: a
      cohort study.
AB  - BACKGROUND: The infant microbiota may play a pathogenic role in coeliac disease
      (CD). Antibiotic treatment in pregnancy is common and could significantly impact
      the infant microbiota. In this study, we aimed to investigate the association
      between antibiotic exposure during pregnancy and CD in offspring. METHODS:
      Prospective questionnaire data on antibiotic exposure in pregnancy were available
      in 8729 children participating in the All Babies in Southeast Sweden (ABIS)
      cohort study, and of these 46 developed CD until December 2006. Cox regression
      estimated hazard ratios (HRs) for CD in the offspring among mothers exposed to
      antibiotics during pregnancy, with adjustment for parent-reported diary data on
      breastfeeding, age at gluten introduction and number of infections in the child's
      first year of life. RESULTS: Of the 1836 children exposed to antibiotics during
      pregnancy, 12 (0.7%) children developed CD as compared with 34/6893 (0.5%)
      unexposed children (HR = 1.33; 95% CI = 0.69-2.56). Risk estimates remained
      unchanged after adjustment for breastfeeding, age at gluten introduction and
      infection load in the child's first year of life (HR = 1.28; 95% CI = 0.66-2.48).
      CONCLUSIONS: We found no statistically significant association between antibiotic
      exposure during pregnancy and CD in offspring. This lack of association may
      either be true or the result of limited statistical power.

PMID- 24731165
TI  - Survival of recipients of livers from donation after circulatory death who are
      relisted and undergo retransplant for graft failure.
AB  - Use of grafts from donation after circulatory death (DCD) as a strategy to
      increase the pool of transplantable livers has been limited due to poorer
      recipient outcomes compared with donation after brain death (DBD). We examined
      outcomes of recipients of failed DCD grafts who were selected for relisting with
      regard to waitlist mortality and patient and graft survival after retransplant.
      From the Scientific Registry of Transplant Recipients database, we identified
      1820 adults who underwent first deceased donor liver transplant January 1, 2004
      to June 30, 2011, and were relisted due to graft failure; 12.7% were DCD
      recipients. Compared with DBD recipients, DCD recipients had better waitlist
      survival (90-day mortality: 8%, DCD recipients; 14-21%, DBD recipients). Of 950
      retransplant patients, 14.5% were prior DCD recipients. Graft survival after
      second liver transplant was similar for prior DCD (28% graft failure within 1
      year) and DBD recipients (30%). Patient survival was slightly better for prior
      DCD (25% death within 1 year) than DBD recipients (28%). Despite higher overall
      graft failure and morbidity rates, survival of prior DCD recipients who were
      selected for relisting and retransplant was not worse than survival of DBD
      recipients. 

PMID- 24731168
TI  - Gastrointestinal involvement in Parkinson's disease: the horse or the cart.

PMID- 24731169
TI  - Abstracts of the 2nd International Meeting on Ischemia Reperfusion Injury in
      Transplantation - IMIRT 2014, 24-25 April 2014, Poitiers, France.

PMID- 24731167
TI  - Comparative normal/failing rat myocardium cell membrane chromatographic analysis
      system for screening specific components that counteract doxorubicin-induced
      heart failure from Acontium carmichaeli.
AB  - Cell membrane chromatography (CMC) derived from pathological tissues is ideal for
      screening specific components acting on specific diseases from complex medicines
      owing to the maximum simulation of in vivo drug-receptor interactions. However,
      there are no pathological tissue-derived CMC models that have ever been
      developed, as well as no visualized affinity comparison of potential active
      components between normal and pathological CMC columns. In this study, a novel
      comparative normal/failing rat myocardium CMC analysis system based on online
      column selection and comprehensive two-dimensional (2D) chromatography/monolithic
      column/time-of-flight mass spectrometry was developed for parallel comparison of
      the chromatographic behaviors on both normal and pathological CMC columns, as
      well as rapid screening of the specific therapeutic agents that counteract
      doxorubicin (DOX)-induced heart failure from Acontium carmichaeli (Fuzi). In
      total, 16 potential active alkaloid components with similar structures in Fuzi
      were retained on both normal and failing myocardium CMC models. Most of them had
      obvious decreases of affinities on failing myocardium CMC compared with normal
      CMC model except for four components, talatizamine (TALA), 14-acetyl-TALA,
      hetisine, and 14-benzoylneoline. One compound TALA with the highest affinity was
      isolated for further in vitro pharmacodynamic validation and target
      identification to validate the screen results. Voltage-dependent K(+) channel was
      confirmed as a binding target of TALA and 14-acetyl-TALA with high affinities.
      The online high throughput comparative CMC analysis method is suitable for
      screening specific active components from herbal medicines by increasing the
      specificity of screened results and can also be applied to other biological
      chromatography models. 

PMID- 24731170
TI  - Commentary: ILAE Definition of Epilepsy.

PMID- 24731171
TI  - Monocyte activation from interferon-alpha in HIV infection increases acetylated
      LDL uptake and ROS production.
AB  - Atherosclerosis is an inflammatory disease that is accelerated in human
      immunodeficiency virus (HIV) infection. Individuals with HIV infection have an
      activated type I interferon (IFN) monocyte phenotype, which may enhance uptake of
      modified low-density lipoprotein (LDL) thereby initiating a prefoam cell
      pathology and recruitment into atherosclerotic plaques. In a sampling of HIV
      infected subjects, an increase in monocyte activation genes, MX1 and CXCL10,
      correlated with monocyte expression of the scavenger receptor A (SR-A), a major
      receptor for lipid uptake and foam cell formation. Monocytes from HIV-infected
      subjects accumulated more lipid than control uninfected subjects. We modeled
      increased activation in HIV infection by priming human monocytes with IFNalpha
      followed by exposure to acetylated LDL (acLDL). Exposure to IFNalpha increased
      acLDL uptake, which generated increased cellular reactive oxygen species (ROS).
      We posit that HIV infection augments formation of arterial plaques by triggering
      monocyte activation with a type I IFN profile, which induces SR-A expression,
      lipid uptake, and subsequent ROS production. These findings may explain in part
      why HIV-infected individuals with chronic immune activation have an increased
      risk of atherosclerosis. 

PMID- 24731172
TI  - Assessment of decision-making performance and in-game physical exertion of
      Australian football umpires.
AB  - The aim of this study is to investigate the effects of in-game physical exertion
      on decision-making performance of Australian football umpires. Fifteen Australian
      football umpires (Mage = 36, s = 13.5 years; Mgames umpired = 235.2, s = 151.3)
      volunteered to participate in the study. During five competitive Australian
      football pre-season games, measures of in-game physical exertion (blood lactate
      levels, global positioning system [GPS]) and decision-making performance (video
      based test) were obtained. There were no significant correlations between
      physical exertion in a particular quarter and decision-making performance in
      either the same quarter or any other quarter. Video-based decision-making
      performance was effected by time in game chi(2)(3) = 24.24, P = 0.001, with
      Quarter 4 performance significantly better than both Quarter 2 and Quarter 3. In
      game physical exertion (blood lactate) significantly decreased over the course of
      the game chi(2)(3) = 11.58, P = 0.009. Results indicate no definable link between
      in-game physical exertion and decision-making performance. It is, however,
      presumed that decision-making performance may be affected by the time or context
      of the game. Future research is warranted to explore the relationship between
      physical exertion and decision-making performance to potentially inform
      Australian football umpire training programmes that replicate in-game physical
      and decision-making demands.

PMID- 24731158
TI  - Health-related quality of life of people living with HIV followed up in hospitals
      in France: comparing trends and correlates between 2003 and 2011 (ANRS-VESPA and
      VESPA2 national surveys).
AB  - In recent years, France has witnessed both structural changes in the population
      of people living with HIV and a relative improvement in the social representation
      of HIV infection. However, potential changes in people's day-to-day experience
      with HIV have not been documented. We used data from the national surveys ANRS
      VESPA (2003) and VESPA2 (2011) to compare the levels and patterns of correlates
      of health-related quality of life (HRQL) in adult HIV-infected patients followed
      up in French hospitals over a period of eight years. Mean physical and mental SF
      12 scores were compared (VESPA, n = 2072; and VESPA2, n = 2267) using analysis of
      variance (ANOVA) F tests. Heckman regression models were then used to identify
      independent correlates of physical and mental quality of life in the two surveys,
      while accounting for possible bias due to missing score values. A common set of
      potential socio-demographic, clinical, behavioral, and psychosocial correlates
      was tested. Individuals reported a decrease in physical quality of life in VESPA2
      compared with VESPA (mean score (standard error): 47.5 (0.2) versus 49.6 (0.2), p
      < .0001), and better mental HRQL (44.3 (0.3) versus 42.3 (0.3), p < 0.0001). In
      both surveys, financial difficulties and patient-perceived experience of
      rejection behaviors by medical staff were independently associated with impaired
      physical and mental quality of life. Older age and unemployment were
      independently associated with impaired physical quality of life. Immigrants from
      Sub-Saharan Africa reported better mental quality of life. Findings show that
      quality of life levels in adult HIV-infected patients followed up at hospital in
      France has significantly, yet modestly, changed in recent years. However, the
      pattern of quality of life correlates has remained relatively stable. The impact
      of patient-provider relationships on self-reported outcomes is confirmed. Further
      research is needed to identify potential differences in quality of life
      correlates in specific subgroups of patients, such as men who have sex with men,
      women, immigrants, and injecting drug users. 

PMID- 24731173
TI  - Modeling nanoparticle-alveolar epithelial cell interactions under breathing
      conditions using captive bubble surfactometry.
AB  - Many advances have been made in recent years in cell culture models of the
      epithelial barrier of the lung from simple monolayers to complex 3-D systems
      employing different cell types. However, the vast majority of these models still
      present a static air-liquid interface which is unrealistic given the dynamic
      nature of breathing. We present here a method where epithelial lung cells are
      integrated into a system, the captive bubble surfactometer, which allows the
      cyclical compression and expansion of the surfactant film at the air-liquid
      interface, thus modeling the dynamics of breathing. We found that cellular uptake
      of deposited gold nanoparticles was significantly increased under the dynamic
      (breathing) conditions of compression and expansion as compared to static
      conditions. The method could be very useful for studying nanoparticle-alveolar
      lung cell interactions under breathing conditions for applications in
      nanomedicine and toxicology. 

PMID- 24731174
TI  - Copy number variation detection using next generation sequencing read counts.
AB  - BACKGROUND: A copy number variation (CNV) is a difference between genotypes in
      the number of copies of a genomic region. Next generation sequencing (NGS)
      technologies provide sensitive and accurate tools for detecting genomic
      variations that include CNVs. However, statistical approaches for CNV
      identification using NGS are limited. We propose a new methodology for detecting
      CNVs using NGS data. This method (henceforth denoted by m-HMM) is based on a
      hidden Markov model with emission probabilities that are governed by mixture
      distributions. We use the Expectation-Maximization (EM) algorithm to estimate the
      parameters in the model. RESULTS: A simulation study demonstrates that our
      proposed m-HMM approach has greater power for detecting copy number gains and
      losses relative to existing methods. Furthermore, application of our m-HMM to DNA
      sequencing data from the two maize inbred lines B73 and Mo17 to identify CNVs
      that may play a role in creating phenotypic differences between these inbred
      lines provides results concordant with previous array-based efforts to identify
      CNVs. CONCLUSIONS: The new m-HMM method is a powerful and practical approach for
      identifying CNVs from NGS data.

PMID- 24731175
TI  - Primary invasive carcinoma associated with penoscrotal extramammary Paget's
      disease: a clinicopathological analysis of 56 cases.
AB  - OBJECTIVES: To investigate the clinicopathological features, therapeutic
      strategies, and prognostic factors of patients with penoscrotal invasive
      extramammary Paget's disease (EMPD). PATIENTS AND METHODS: We retrospectively
      collected clinical, pathological, and follow-up data of 56 men with invasive
      penoscrotal EMPD. Histopathological features of the primary skin lesion including
      tumour size, surgical margin status, depth of invasion and lymphovascular
      invasion were examined. RESULTS: The median age was 67 years and median longest
      diameter of lesion was 5 cm. All patients were treated with wide surgical
      excision and 22 patients with clinically positive regional lymph nodes underwent
      therapeutic regional lymph node dissection. At the end of the study, 44.6% of
      patients developed distant metastasis and 39.3% of patients had died from
      disease. Univariate analysis showed that patients with one of the following poor
      prognostic factors: depth of invasion of lower dermis or deeper, presence of
      lymphovascular invasion and regional lymph node metastasis at diagnosis, had
      significantly shorter cancer-specific survival time. Multivariate analysis found
      that depth of invasion was the only independent prognostic factor. CONCLUSION:
      The prognosis of invasive EMPD is significantly associated with depth of
      invasion, lymphovascular invasion and regional lymph node status. More aggressive
      therapy and more rigorous follow-up should be recommended for patients with these
      poor prognostic factors.

PMID- 24731177
TI  - Transatlantic health IT policies: opportunities for small businesses and health
      systems.

PMID- 24731178
TI  - The dynamics of shared leadership: building trust and enhancing performance.
AB  - In this study, we examined how the dynamics of shared leadership are related to
      group performance. We propose that, over time, the expansion of shared leadership
      within groups is related to growth in group trust. In turn, growth in group trust
      is related to performance improvement. Longitudinal data from 142 groups engaged
      in a strategic simulation game over a 4-month period provide support for positive
      changes in trust mediating the relationship between positive changes in shared
      leadership and positive changes in performance. Our findings contribute to the
      literature on shared leadership and group dynamics by demonstrating how the
      growth in shared leadership contributes to the emergence of trust and a positive
      performance trend over time.

PMID- 24731176
TI  - Patterns of surgical care and complications in elderly adults.
AB  - OBJECTIVES: To determine whether procedures, hospitals visited, and complications
      would differ according to decade in elderly adults and from those of younger
      adults. DESIGN: Retrospective cohort study. SETTING: The Anesthesia Quality
      Institute National Anesthesia Clinical Outcomes Registry (NACOR) is the largest
      database of anesthesia cases from academic and community hospitals and includes
      all insurance and facility types across the United States. PARTICIPANTS: Eight
      million six hundred thirty-two thousand nine hundred seventy-nine cases from
      January 2010 to March 2013 were acquired. After exclusion of individuals younger
      than 18, nonapplicable locations, and brain death, 2,851,114 remained and were
      placed into age categories (18-64, 65-69, 70-79, 80-89, >= 90). MEASUREMENTS:
      Participant, surgical, anesthetic, and hospital descriptors and short-term
      outcomes (major complications, mortality at <48 hours). RESULTS: The largest
      number of older adults had surgery in medium-sized community hospitals. The
      oldest age group (>= 90) underwent the smallest range of procedures; hip
      fracture, hip replacement, and cataract procedures accounted for more than 35% of
      all surgeries. Younger old adults underwent these procedures plus a significant
      proportion of spinal fusion, cholecystectomy, and knee surgery. Older adults had
      greater mortality and more complications than younger adults. Participants
      undergoing exploratory laparotomy had the greatest likelihood of death in any age
      category except 90 and older, in which small bowel resection predominated. The
      proportion of emergency surgery and the mortality associated with emergency
      surgery was 30% higher in the oldest group (>= 90) than in adults aged 18 to 64.
      CONCLUSION: This article reports the pattern of surgical procedures,
      complications, and mortality found in NACOR, which is one of the few data sets
      that contains data from community hospitals and individuals with all types of
      insurance. Because the outcomes portion of the data set is under development, it
      is not possible to investigate the relationship between hospital type and
      complications or mortality, but this study underscores the magnitude of geriatric
      surgery that occurs in community hospitals as an area for future outcomes
      studies.

PMID- 24731179
TI  - Roots run deep: Investigating psychological mechanisms between history of family
      aggression and abusive supervision.
AB  - In this article, we examine the relationships between supervisor-level factors
      and abusive supervision. Drawing from social learning theory (Bandura, 1973), we
      argue that supervisors' history of family aggression indirectly impacts abusive
      supervision via both hostile cognitions and hostile affect, with angry rumination
      functioning as a first-stage moderator. Using multisource data, we tested the
      proposed relationships in a series of 4 studies, each providing evidence of
      constructive replication. In Study 1, we found positive relationships between
      supervisors' history of family aggression, hostile affect, explicit hostile
      cognitions, and abusive supervision. We obtained the same pattern of results in
      Studies 2, 3, and 4 using an implicit measure of hostile cognitions and
      controlling for previously established antecedents of abusive supervision. Angry
      rumination moderated the indirect relationship between supervisors' history of
      family aggression and abusive supervision via hostile affect only. Overall, the
      results highlight the important role of supervisor-level factors in the abusive
      supervision dynamics.

PMID- 24731180
TI  - Small sample mediation testing: misplaced confidence in bootstrapped confidence
      intervals.
AB  - Bootstrapping is an analytical tool commonly used in psychology to test the
      statistical significance of the indirect effect in mediation models.
      Bootstrapping proponents have particularly advocated for its use for samples of
      20-80 cases. This advocacy has been heeded, especially in the Journal of Applied
      Psychology, as researchers are increasingly utilizing bootstrapping to test
      mediation with samples in this range. We discuss reasons to be concerned with
      this escalation, and in a simulation study focused specifically on this range of
      sample sizes, we demonstrate not only that bootstrapping has insufficient
      statistical power to provide a rigorous hypothesis test in most conditions but
      also that bootstrapping has a tendency to exhibit an inflated Type I error rate.
      We then extend our simulations to investigate an alternative empirical resampling
      method as well as a Bayesian approach and demonstrate that they exhibit
      comparable statistical power to bootstrapping in small samples without the
      associated inflated Type I error. Implications for researchers testing mediation
      hypotheses in small samples are presented. For researchers wishing to use these
      methods in their own research, we have provided R syntax in the online
      supplemental materials.

PMID- 24731181
TI  - Observing workplace incivility.
AB  - Interpersonal mistreatment at work often occurs in the presence of others;
      however, these "others" are rarely examined in empirical research despite their
      importance to the context of the negative interaction. We conducted 2 experiments
      to examine how witnessing incivility affects observer reactions toward
      instigators and targets. In Study 1, participants (N = 60) worked virtually with
      an ostensible instigator and target. In Study 2, participants (N = 48) worked in
      vivo with confederates (hired actors) on a job task. Across these 2 studies, we
      found that observers of incivility tend to punish instigators while their
      reactions to targets were generally unaffected. Further, the effect of witnessing
      incivility was mediated by observers' negative emotional reaction toward the
      instigator.

PMID- 24731182
TI  - Solid-state magnetic switching triggered by proton-coupled electron-transfer
      assisted by long-distance proton-alkali cation transport.
AB  - Acidity of water molecules coordinated to Co ions in CoFe Prussian blue analogues
      (PBA) has been used to reversibly activate the Co(III)Fe(II) <-> Co(II)Fe(III)
      electron transfer. The study of the structure and the electronic structure shows
      that the process implies an original PCET reaction between a solid-state porous
      coordination polymer and hydroxide ions in solution. The PCET reaction spreads
      throughout the solid network thanks to a long-range H(+) and Rb(+) transport
      within the pore channels of PBA taking advantage of the hydrogen-bonding network
      of zeolitic water molecules acting as proton wires. 

PMID- 24731183
TI  - Biophysical implications of sphingosine accumulation in membrane properties at
      neutral and acidic pH.
AB  - Sphingosine (Sph) is a simple lipid involved in the regulation of several
      biological processes. When accumulated in the late endosomal/lysosomal
      compartments, Sph causes changes in ion signaling and membrane trafficking,
      leading to the development of Niemann-Pick disease type C. Little is known about
      Sph interaction with other lipids in biological membranes; however, understanding
      the effect of Sph in the physical state of membranes might provide insights into
      its mode of action. Using complementary established fluorescence approaches, we
      show that Sph accumulation leads to the formation of Sph-enriched gel domains in
      1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) and POPC/sphingomyelin
      (SM)/cholesterol (Chol) model membranes. These domains are more easily formed in
      membrane models mimicking the neutral pH plasma membrane environment (PM) as
      compared to the acidic lysosomal membrane environment (LM), where higher Sph
      concentrations (or lower temperatures) are required. Electrophoretic light
      scattering measurements further revealed that in PM-raft models (POPC/SM/Chol),
      Sph is mainly neutral, whereas in LM models, the positive charge of Sph leads to
      electrostatic repulsion, reducing the Sph ability to form gel domains. Thus,
      formation of Sph-enriched domains in cellular membranes might be strongly
      regulated by Sph charge. 

PMID- 24731184
TI  - Effects of Verbal Ability and Severity of Autism on Anxiety in Adolescents With
      ASD: One-Year Follow-Up After Cognitive Behavioral Therapy.
AB  - There is evidence supporting the efficacy of cognitive-behavioral therapy for
      treatment of anxiety in youth with Autism Spectrum Disorders (ASD), but long-term
      course of anxiety after treatment and individual predictors of treatment response
      are unknown. To meet the demands for personalized mental health care, information
      on the fit between patient and treatment as well as treatment durability is
      needed. We evaluated change in anxiety symptoms during intervention and 1 year
      after completion of the treatment, and evaluated predictors of response using an
      advanced analytical design, with follow-up data from a randomized controlled
      trial of 22 adolescents (12-17 years) with ASD and 1 or more anxiety disorders.
      Reduction in anxiety was partially maintained during the year following
      treatment; greater ASD severity predicted better treatment response. Our finding
      that brief treatment is associated with sustained gains is promising, given the
      pervasive and chronic nature of ASD. Implications for the treatment of anxiety in
      higher functioning adolescents with ASD are considered. 

PMID- 24731185
TI  - Comparing long-term care recipients in urban and rural municipalities in Japan
      and Sweden.
AB  - Japan and Sweden both have national systems of long-term care (LTC) and face
      similar challenges. This study compared various indicators of disability in LTC
      recipients in nine large urban, midsize urban, and rural municipalities in both
      countries. The aim was to establish whether urban-rural differences exist and
      whether they follow similar patterns in Japan and Sweden. It was found that LTC
      recipients in large urban municipalities in both countries were on average
      significantly less disabled than those from the other types of municipalities,
      regardless of the indicator for disability. Fewer persons in large urban
      municipalities live in extended families, which may increase the propensity to
      apply for LTC. The number of older people living alone in Japan is increasing,
      which means that the formal LTC system will come under increased pressure. 

PMID- 24731187
TI  - Preparation and flammability of poly(vinyl alcohol) composite aerogels.
AB  - Poly(vinyl alcohol) (PVOH)-based aerogel composites with nanoscale silica,
      halloysite, montmorillonite (MMT), and laponite were prepared via a freeze-drying
      method. The PVOH/MMT and PVOH/laponite composites exhibit higher compressive
      moduli than the PVOH/SiO2 or PVOH/halloysite samples. Layered microstructures
      were observed for the samples except with PVOH/laponite, which showed irregular
      network morphologies. Thermogravimetric analysis of the aerogel samples showed
      increased thermal stability with the addition of nanofillers. The heat release
      measured by cone calorimetry, smoke release, and carbon monoxide production of
      the aerogel composites are all significantly decreased with the addition of
      nanofillers; these values are much lower than those for commercial expanded
      polystyrene foam. The fillers did not lead to obvious increases in the limiting
      oxygen index values, and the corresponding time to ignition values decrease. The
      ability to adjust the nanofiller levels in these foamlike aerogel composites
      allows for specific tuning of these products for fire safety. 

PMID- 24731186
TI  - CD34(+) cell therapy is safe and effective in slowing the decline of hepatic
      reserve function in patients with decompensated liver cirrhosis.
AB  - BACKGROUND AND AIM: Preclinical studies in rodent models of chronic liver
      fibrosis have shown that transplantation of peripheral blood (PB) CD34(+) cells
      leads to hepatic regeneration and a reduction of liver fibrosis by suppressing
      hepatic stellate cell activity and increasing matrix metalloproteinase activity.
      The aim of this study was to examine the safety and clinical efficacy of
      intrahepatic transplantation of autologous granulocyte colony-stimulating factor
      (G-CSF)-mobilized PB-CD34(+) cells in patients with decompensated liver
      cirrhosis. METHODS: PB-CD34(+) cells were isolated from G-CSF-mobilized apheresis
      products. Ten patients were treated with G-CSF-mobilized PB-CD34(+) cells
      (treatment group) and seven patients were treated with standard medical therapy.
      For mobilization, patients in the treatment group received subcutaneous
      injections of 10 MUg G-CSF/kg/day for 5 days. The cells were then injected at
      three different doses (5 * 10(5) , 1 * 10(6) and 2 * 10(6) cells/kg) through the
      hepatic artery. Thereafter, all patients were followed up for 24 months. RESULTS:
      G-CSF treatment and leukapheresis were well tolerated, and no serious adverse
      events were observed. Patients in the treatment group had a significant but
      transient splenomegaly. After 24 weeks, serum albumin was significantly increased
      in patients who had received middle or high doses of CD34(+) cells compared with
      baseline. Doppler ultrasound showed a significant increase in hepatic blood flow
      velocity and blood flow volume after CD34(+) cell therapy. The hepatic vein
      pressure gradient decreased in two patients who received high-dose CD34(+) cells
      at week 16. CONCLUSIONS: CD34(+) cell therapy is feasible, safe and effective in
      slowing the decline of hepatic reserve function.

PMID- 24731188
TI  - Effect of leptin on in vivo goat embryo production.
AB  - The aim of this study was to evaluate the effect of leptin administration during
      superovulation on in vivo goat embryo production. Ten mature does were
      superovulated with 133 mg follicle-stimulating hormone (FSH) i.m. in six
      descending doses at 12-h intervals. The goats received 4.8 MUg/kg human
      recombinant leptin s.c. (leptin group, n = 5) or phosphate-buffered saline (PBS)
      (control group, n = 5) with the first and second FSH doses. The does were mated
      and subjected to embryo collection by transcervical technique 6 days later. The
      total number of cells per embryo and the number of cells with fragmented DNA were
      assessed in selected blastocysts by combining Hoechst 33342 and terminal dUTP
      nick-end labelling (TUNEL) staining. Plasma concentrations of oestradiol (E2 )
      and progesterone (P4 ) were determined by electrochemiluminescence from the day
      of FSH treatment, on the day of superovulatory oestrus and on the day before
      embryo collection. Compared with the control group, the does that received leptin
      had a higher number of transferable embryos (p < 0.005), fewer embryos classified
      as degenerated (p < 0.001) and fewer TUNEL-positive cells/blastocyst (p < 0.001).
      The number of transferable embryos was positively correlated with E2
      concentrations on day of oestrus (r = 0.562; p < 0.01) and P4 concentrations on
      the day of embryo collection (r = 0.912; p < 0.001). We concluded that in vivo
      leptin administration during FSH treatment improved embryo quality and affected
      ovarian steroidogenesis in superovulated goats. 

PMID- 24731189
TI  - Factors associated with functional incapacity in elders living in long stay
      institutions in Brazil: a cross-sectional study.
AB  - BACKGROUND: The increase of the elderly population and the high prevalence of
      chronic diseases have contributed to the increasing importance of functional
      ability as a global public health problem. This study aimed to assess functional
      capacity in institutionalized elders, as well as undertake an exploratory
      analysis of its associated factors. METHODS: This is a cross-sectional study with
      institutionalized Brazilian elders. Functional capacity was assessed using the
      Katz Index for Activities of Daily Living (ADL) and the Lawton Scale for
      Instrumental Activities of Daily Living (IADL). The characteristics of dependent
      individuals were described and logistic regression models were developed for both
      scales. Multiple models that included all selected variables were developed using
      a hierarchical approach. We considered the results from the Wald test (p <0.05)
      as a rule for progressing to the next level. RESULTS: A population of 760 elders
      was considered. The prevalence of dependence was 50.3% for ADL and 81.2% for
      IADL. We observed associations between ADL dependence and the following factors:
      self-report of stroke, difficulty of walking 400 meters, lower total scores in
      questions related to the temporal orientation section of the cognition test, and
      self-reports of frequently feeling upset. IADL dependence was associated with
      educational level, self-report of cancer, difficulty of walking 400 meters, use
      of glasses, and self-reported memory problems. CONCLUSIONS: Sociodemographic and
      health conditions were associated with functional incapacity in institutionalized
      elders. Based on these findings, we emphasize the importance of both prevention
      and treatment of chronic conditions as well as social support in the maintenance
      of individuals' autonomy.

PMID- 24731190
TI  - Access to retransplantation after failed donation after circulatory death liver
      transplantation: eo ire itum.

PMID- 24731191
TI  - The effect of breed and sex on sulfamethazine, enrofloxacin, fenbendazole and
      flunixin meglumine pharmacokinetic parameters in swine.
AB  - Drug use in livestock has received increased attention due to welfare concerns
      and food safety. Characterizing heterogeneity in the way swine populations
      respond to drugs could allow for group-specific dose or drug recommendations. Our
      objective was to determine whether drug clearance differs across genetic
      backgrounds and sex for sulfamethazine, enrofloxacin, fenbendazole and flunixin
      meglumine. Two sires from each of four breeds were mated to a common sow
      population. The nursery pigs generated (n = 114) were utilized in a random
      crossover design. Drugs were administered intravenously and blood collected a
      minimum of 10 times over 48 h. A non-compartmental analysis of drug and
      metabolite plasma concentration vs. time profiles was performed. Within-drug and
      metabolite analysis of pharmacokinetic parameters included fixed effects of drug
      administration date, sex and breed of sire. Breed differences existed for
      flunixin meglumine (P-value<0.05; Cl, Vdss ) and oxfendazole (P-value<0.05, AUC0
      >infinity ). Sex differences existed for oxfendazole (P-value < 0.05; Tmax ) and
      sulfamethazine (P-value < 0.05, Cl). Differences in drug clearance were seen, and
      future work will determine the degree of additive genetic variation utilizing a
      larger population. 

PMID- 24731192
TI  - Bile deficiency induces changes in intestinal Cl(-) and HCO3 (-) secretions in
      mice.
AB  - AIMS: Biliary tract obstruction is a common clinical lesion. However, the effect
      of biliary tract obstruction on intestinal secretion is poorly understood. In
      this study, we made an investigation on intestinal HCO3 (-) and Cl(-) secretions
      in an experimental model of murine biliary duct ligation. METHODS: Murine
      intestinal mucosal HCO3 (-) and Cl(-) secretions were examined in vitro in Ussing
      chambers by pH-stat and short-circuit current (Isc ) techniques. The mRNA and
      protein expressions of the cystic fibrosis transmembrane conductance regulator
      (CFTR) and the Na(+) -K(+) -2Cl(-) cotransporter (NKCC1) were analysed by real
      time PCR, western blot and immunohistochemistry. RESULTS: Basal Cl(-) secretion
      and forskolin-stimulated duodenal and jejunal mucosal HCO3 (-) and Cl(-)
      secretions in mice with common biliary duct ligation were markedly elevated,
      compared with controls (P < 0.05 and P < 0.01). Further experiments showed that
      basal Cl(-) secretion and forskolin-stimulated duodenal and jejunal mucosal HCO3
      (-) and Cl(-) secretions in mice with external bile drainage were also markedly
      elevated. CFTRinh -172 inhibited forskolin-stimulated HCO3 (-) and Cl(-)
      secretions. The mRNA and protein expression levels of CFTR and NKCC1 in the
      intestinal mucosa with both biliary duct ligation and external bile drainage were
      markedly higher than those in controls (P < 0.001). Bile acid administration
      restored the changes in function and expression of CFTR and NKCC1 in the
      intestinal mucosa. CONCLUSION: Bile deficiency in the intestine up-regulates the
      expressions of intestinal mucosal CFTR and NKCC1 and enhances intestinal mucosal
      HCO3 (-) and Cl(-) secretion capacity, which contributes to the understanding of
      intestinal physiological function for patients with biliary duct obstruction.

PMID- 24731193
TI  - Application of the tissue transfer technique in veterinary cytopathology.
AB  - BACKGROUND: Limited availability of diagnostic cytopathologic material may
      preclude additional diagnostic techniques. Tissue transfer allows for preparation
      of additional slides from a single original slide. Information pertaining to the
      application of the tissue transfer technique in veterinary cytopathology is
      lacking. OBJECTIVES: The objectives were to evaluate the application of the
      tissue transfer technique on Quick Dip-stained veterinary cytologic smears and to
      assess if a selection of histochemical and immunocytochemical stains, and PCR
      analyses could be performed on transferred material. METHODS: Archived Quick Dip
      stained canine lymph node aspirate smears from previously diagnosed lymphoma
      cases were utilized to validate and optimize the tissue transfer technique. In
      this technique, diagnostic material is lifted from the original stained slide, is
      divided and transferred to multiple new slides. Histochemical stains such as
      Gram, periodic acid Schiff, Congo red, and Ziehl-Neelson, immunohistochemistry
      for CD3 and PAX5, and PCR for cryptococcal and mycobacterial organisms were
      selectively performed on transferred material. RESULTS: The tissue transfer
      technique was simple, and transferred Quick Dip-stained material retained
      cellular morphology. Histochemical and immunohistochemical stains, and PCR
      analysis yielded reliable results when performed on the additional smears
      produced by this technique. CONCLUSIONS: The tissue transfer technique was simple
      and easy to perform on previously Quick Dip-stained cytology smears. Cellular
      detail was preserved and multiple additional ancillary diagnostic techniques were
      facilitated, such as histochemical and immunohistochemical stains, and PCR
      analysis.

PMID- 24731195
TI  - Gold-catalyzed oxidative reactions of propargylic carbonates involving 1,2
      carbonate migration: stereoselective synthesis of functionalized alkenes.
AB  - A gold-catalyzed oxidative reaction of propargylic carbonates or acetates using
      3,5-dichloropyridine as the oxidant has been developed. The reaction provides
      efficient access to alpha-functionalized-alpha,beta-unsaturated ketones with
      excellent regio- and diastereocontrol via a regioselective attack of the N-oxide
      to the gold-activated alkyne followed by a 1,2-carbonate migration. In addition,
      the alkene products could be further transformed into the valuable 5
      hydroxycyclopent-2-enones via cyclocondensation with acetone or cyclodimerization
      under basic conditions. 

PMID- 24731194
TI  - Multicolor fluorescent biosensor for multiplexed detection of DNA.
AB  - Development of efficient methods for highly sensitive and rapid screening of
      specific oligonucleotide sequences is essential to the early diagnosis of serious
      diseases. In this work, an aggregated cationic perylene diimide (PDI) derivative
      was found to efficiently quench the fluorescence emission of a variety of anionic
      oligonucleotide-labeled fluorophores that emit at wavelengths from the visible to
      NIR region. This broad-spectrum quencher was then adopted to develop a multicolor
      biosensor via a label-free approach for multiplexed fluorescent detection of DNA.
      The aggregated perylene derivative exhibits a very high quenching efficiency on
      all ssDNA-labeled dyes associated with biosensor detection, having efficiency
      values of 98.3 +/- 0.9%, 97 +/- 1.1%, and 98.2 +/- 0.6% for FAM, TAMRA, and Cy5,
      respectively. An exonuclease-assisted autocatalytic target recycling
      amplification was also integrated into the sensing system. High quenching
      efficiency combined with autocatalytic target recycling amplification afforded
      the biosensor with high sensitivity toward target DNA, resulting in a detection
      limit of 20 pM, which is about 50-fold lower than that of traditional unamplified
      homogeneous fluorescent assay methods. The quencher did not interfere with the
      catalytic activity of nuclease, and the biosensor could be manipulated in either
      preaddition or postaddition manner with similar sensitivity. Moreover, the
      proposed sensing system allows for simultaneous and multicolor analysis of
      several oligonucleotides in homogeneous solution, demonstrating its potential
      application in the rapid screening of multiple biotargets. 

PMID- 24731196
TI  - Modulation of the sensitivity of Jurkat T-cells to inhibition of protein
      synthesis by tumor necrosis factor alpha-related apoptosis-inducing ligand.
AB  - Tumor necrosis factor alpha-related apoptosis-inducing ligand (TRAIL) is a potent
      inducer of apoptosis in Jurkat T lymphoma cells. One of the characteristics of
      the phase preceding overt apoptosis is the marked downregulation of protein
      synthesis. We have investigated factors that can influence this response and have
      explored some of the signaling pathways involved. We show that interferon-alpha
      (IFNalpha) pretreatment desensitizes Jurkat cells to TRAIL-induced inhibition of
      protein synthesis, such that the concentration of TRAIL required for 50%
      inhibition is increased by 10-fold. The inhibition of translation is
      characterized by dephosphorylation of the eIF4E-binding protein 4E-BP1 and
      IFNalpha desensitizes Jurkat cells to this effect. IFNalpha also inhibits TRAIL
      mediated dephosphorylation of the growth-promoting protein kinase B (Akt). Since
      Jurkat cells are defective for phosphatase and tensin homolog deleted on
      chromosome 10 (PTEN) and therefore have constitutive phosphoinositide 3-kinase
      (PI3K) activity, we investigated the consequences for protein synthesis of
      inhibiting PI3K using LY294002. Inhibition of PI3K partially inhibits
      translation, but also enhances the effect of a suboptimal concentration of TRAIL.
      However, LY294002 does not block the ability of IFNalpha to protect protein
      synthesis from TRAIL-induced inhibition. Data are presented suggesting that
      IFNalpha impairs the process of activation of caspase-8 within the TRAIL death
      inducing signaling complex. 

PMID- 24731197
TI  - Longitudinal trends in prostate cancer incidence, mortality, and survival of
      patients from two Shanghai city districts: a retrospective population-based
      cohort study, 2000-2009.
AB  - BACKGROUND: Prostate cancer is the fifth most common cancer affecting men of all
      ages in China, but robust surveillance data on its occurrence and outcome is
      lacking. The specific objective of this retrospective study was to analyze the
      longitudinal trends of prostate cancer incidence, mortality, and survival in
      Shanghai from 2000 to 2009. METHODS: A retrospective population-based cohort
      study was performed using data from a central district (Putuo) and a suburban
      district (Jiading) of Shanghai. Records of all prostate cancer cases reported to
      the Shanghai Cancer Registry from 2000 to 2009 for the two districts were
      reviewed. Prostate cancer outcomes were ascertained by matching cases with
      individual mortality data (up to 2010) from the National Death Register. The Cox
      proportional hazards model was used to analyze factors associated with prostate
      cancer survival. RESULTS: A total of 1022 prostate cancer cases were diagnosed
      from 2000 to 2009. The average age of patients was 75 years. A rapid increase in
      incidence occurred during the study period. Compared with the year 2000, 2009
      incidence was 3.28 times higher in Putuo and 5.33 times higher in Jiading.
      Prostate cancer mortality declined from 4.45 per 105 individuals per year in 2000
      to 1.94 per 105 in 2009 in Putuo and from 5.45 per 105 to 3.5 per 105 in Jiading
      during the same period. One-year and 5-year prostate cancer survival rates were
      95% and 56% in Putuo, and 88% and 51% in Jiading, respectively. Staging of
      disease, Karnofsky Performance Scale Index, and selection of chemotherapy were
      three independent factors influencing the survival of prostate cancer patients.
      CONCLUSIONS: The prostate cancer incidence increased rapidly from 2000 to 2009,
      and prostate cancer survival rates decreased in urban and suburban Chinese
      populations. Early detection and prompt prostate cancer treatment is important
      for improving health and for increasing survival rates of the Shanghai male
      population.

PMID- 24731199
TI  - Rethinking Medicare: some rural considerations.

PMID- 24731198
TI  - On finding bicliques in bipartite graphs: a novel algorithm and its application
      to the integration of diverse biological data types.
AB  - BACKGROUND: Integrating and analyzing heterogeneous genome-scale data is a huge
      algorithmic challenge for modern systems biology. Bipartite graphs can be useful
      for representing relationships across pairs of disparate data types, with the
      interpretation of these relationships accomplished through an enumeration of
      maximal bicliques. Most previously-known techniques are generally ill-suited to
      this foundational task, because they are relatively inefficient and without
      effective scaling. In this paper, a powerful new algorithm is described that
      produces all maximal bicliques in a bipartite graph. Unlike most previous
      approaches, the new method neither places undue restrictions on its input nor
      inflates the problem size. Efficiency is achieved through an innovative
      exploitation of bipartite graph structure, and through computational reductions
      that rapidly eliminate non-maximal candidates from the search space. An iterative
      selection of vertices for consideration based on non-decreasing common
      neighborhood sizes boosts efficiency and leads to more balanced recursion trees.
      RESULTS: The new technique is implemented and compared to previously published
      approaches from graph theory and data mining. Formal time and space bounds are
      derived. Experiments are performed on both random graphs and graphs constructed
      from functional genomics data. It is shown that the new method substantially
      outperforms the best previous alternatives. CONCLUSIONS: The new method is
      streamlined, efficient, and particularly well-suited to the study of huge and
      diverse biological data. A robust implementation has been incorporated into
      GeneWeaver, an online tool for integrating and analyzing functional genomics
      experiments, available at http://geneweaver.org. The enormous increase in
      scalability it provides empowers users to study complex and previously
      unassailable gene-set associations between genes and their biological functions
      in a hierarchical fashion and on a genome-wide scale. This practical
      computational resource is adaptable to almost any applications environment in
      which bipartite graphs can be used to model relationships between pairs of
      heterogeneous entities.

PMID- 24731200
TI  - Impact and outcomes of a rural Personal Helpers and Mentors service.
AB  - OBJECTIVE: To describe impacts and outcomes associated with the Personal Helpers
      and Mentor's (PHaMs) service in a rural Australian town. DESIGN: A descriptive
      analysis of longitudinal data, uncontrolled pre-test and post-test caseworker
      ratings, and retrospective pre-test/post-test self-ratings and feedback comments
      were collected from convenience samples. SETTING: A community-based mental health
      recovery service. PARTICIPANTS: n=76 mental health consumers; mean age=37.78
      years; 45% male; 63% Aboriginal; primary diagnoses=41% psychotic disorder and 61%
      mood disorder; co-morbid diagnosis=45% substance use disorder. INTERVENTIONS:
      Individual recovery plan (IRP), personal goal setting, caseworker mentoring and
      support. MAIN OUTCOME MEASURES: Gains towards goals, the Role Functioning Scale
      (RFS), self-ratings and feedback comments. RESULTS: The most frequently addressed
      goals were: attend mental health treatment services, acquire suitable
      accommodation and be more involved in the community. IRP completers (n=19) showed
      a significant improvement in caseworker-rated adaptive functioning which was
      adequate at case closure (t(18)=-4.38, P<0.001). Participant (n=19) ratings of
      the service and its key performance indicators suggested global satisfaction and
      gains in the management of everyday tasks, use of medications and community
      engagement. Good rapport was reported with the locally trained and predominantly
      Aboriginal (56%) staff. CONCLUSIONS: PHaMs shows promise for assisting rural
      people with mental illness to improve their everyday functioning, medication
      management and community involvement. Recruitment and capacity-building of
      Aboriginal staff appears to facilitate Aboriginal consumer participation.

PMID- 24731201
TI  - Factors driving James Cook University Bachelor of Medicine, Bachelor of Surgery
      graduates' choice of internship location and beyond.
AB  - OBJECTIVE: To identify the main reason James Cook University (JCU) Bachelor of
      Medicine, Bachelor of Surgery graduates chose their internship location and first
      four practice relocations. DESIGN & PARTICIPANTS: This cross-sectional study
      invited 261 JCU medical graduates to participate in an email or telephone survey.
      MAIN OUTCOME MEASURES: Graduates' main reason for choosing internship location
      and up to four subsequent relocations, post-graduate specialty training
      undertaken and practice location (either metropolitan or non-metropolitan) for
      graduates' internship year and current practice year (2012). RESULTS: Respondents
      (n=175; response rate=67%) reported personal factors as the primary driver for
      choosing their internship location, with 33% returning to 'near their family/home
      town', and 21% staying in the town they were based in Years 5 and 6. Professional
      reasons dominated for subsequent relocations, particularly 'long-term career
      ambitions'. Fifty-nine of the 175 (34%) JCU graduates had undertaken their
      internship in a metropolitan location (Australian Standard Geographical
      Classification Remoteness Area 1), while 80 (46%) currently (in 2012) practised
      in a metropolitan location. Internship location was not associated with later
      specialty training, but current metropolitan practice was associated with
      Surgical or Paediatrics training (P=0.007 and P=0.063, respectively), while
      current non-metropolitan practice was associated with General Practice and Rural
      Generalist training (P=0.010 and P=0.001, respectively). CONCLUSIONS: Personal
      decisions take precedence over professional career decisions for why JCU medical
      graduates chose their internship location, but subsequent relocations are driven
      by career ambitions, usually around specialty training requirements. These
      findings support establishing more post-graduate training opportunities in non
      metropolitan settings for Surgical and Paediatric specialties as a retention
      strategy for a rural medical career.

PMID- 24731202
TI  - Rural experience for junior doctors: is it time to make it mandatory?
AB  - OBJECTIVE: To determine whether rural practice terms for junior doctors result in
      increased interest in rural practice and whether these terms improve learning
      experiences, clinical skills and insight into difficulties of rural practice.
      DESIGN: Semistructured, self-administered survey with questions on respondent
      demographics, clinical experience during rural practice terms, post-rural
      experience and personal opinion. SETTING: South East Queensland. PARTICIPANTS:
      Thirty junior doctors from three tertiary hospitals were approached. The response
      rate was 100%. MAIN OUTCOME MEASURES: Exploration of junior doctors' rural term
      experience. RESULTS: Two thirds (67%) of the respondents reported feeling
      uncomfortable with respect to clinical practice requirements during their rural
      terms. Half (47%) performed procedures they had only previously performed in
      simulation environments, and the majority (87%) relied on textbooks or other
      resources on a daily basis. Two thirds (67%) changed aspects of their usual
      clinical practice while practising in a rural setting, and 80% reported a change
      in attitude towards the hardships faced by rural practitioners. The majority of
      the respondents (87%) enjoyed their rural term, gaining confidence as a result of
      it, and more than half (53%) reported considering working in rural areas in the
      future. CONCLUSIONS: The results of this survey suggest that junior doctors on
      rural rotations are required to perform at a clinical level higher than that
      required of them in metropolitan hospitals. While their clinical experience
      appears to result in a greater interest in future rural career possibilities for
      junior doctors, this survey highlights the requirement to improve support for
      junior doctors undertaking terms in rural areas.

PMID- 24731203
TI  - Financial costs for teaching in rural and urban Australian general practices: is
      there a difference?
AB  - OBJECTIVE: To determine if the financial costs of teaching GP registrars differs
      between rural and urban practices. DESIGN: Cost-benefit analysis of teaching
      activities in private GP for GP vocational training. Data were obtained from a
      survey of general practitioners in South Australia and Western Australia. SETTING
      AND PARTICIPANTS: General practitioners and practices teaching in association
      with the Adelaide to Outback General Practice Training Program or the Western
      Australian General Practice Training. MAIN OUTCOME MEASURES: Net financial effect
      per week per practice. RESULTS: At all the training levels, rural practices
      experienced a financial loss for teaching GP registrars, while urban practices
      made a small financial gain. The differences in net benefit between rural and
      urban teaching practices was significant at the GPT2/PRRT2 (-$515 per week 95% CI
      -$1578, -$266) and GPT3/PRRT3 training levels (-$396 per week, 95% CI (-$2568, 
      $175). The variables contributing greatest to the difference were the higher
      infrastructure costs for a rural practice and higher income to the practice from
      the GP registrars in urban practices. CONCLUSION: There were significant
      differences in the financial costs and benefits for a teaching rural practice
      compared with an urban teaching practice. With infrastructure costs which include
      accommodation, being a key contributor to the difference found, it might be time
      to review the level of incentives paid to practices in this area. If not
      addressed, this cost difference might be a disincentive for rural practices to
      participate in teaching.

PMID- 24731204
TI  - Prevocational exposure to public health in the Kimberley: a pathway to rural,
      remote and public health practice.
AB  - OBJECTIVE: To evaluate the Kimberley Population Health Unit (KPHU) prevocational
      public health placement in terms of its contribution to resident medical
      officers' (RMOs') knowledge, skills, career path and aspirations. DESIGN: All
      RMOs who had completed a public health placement at the KPHU (n=27) during 2001
      2012 were invited to complete an online survey in September 2012. SETTING: The
      KPHU, based in Broome, provides population health services to the Kimberley
      region, far north Western Australia. MAIN OUTCOME MEASURES: The extent to which
      RMOs perceived the development of public health skills and knowledge during the
      placement, and the degree to which RMOs believe this placement influenced future
      career pathways and their current practice. RESULTS: Twenty-three RMOs (85%)
      completed the survey. Sixty per cent are currently working in general practice or
      public health medicine; of these, 43% have returned to the Kimberley. Over 70%
      reported that the placement developed their knowledge of public health and
      Aboriginal health to a 'great' or 'very great' extent. Sixty-one per cent felt
      that their placement influenced their future desire to work in public health 'a
      lot' or 'a great extent'. CONCLUSION: This placement provides a unique
      opportunity for RMOs to undertake public health and Aboriginal health work in a
      remote setting. Given the increasing demand for prevocational placements, the
      value of imparting sound public health knowledge to the next generation of
      doctors and the urgent need to recruit and retain rural doctors, this placement
      provides a potential model that could be expanded to other locations.

PMID- 24731205
TI  - Clinical scholarship among preceptors supervising longitudinal integrated medical
      clerkships in regional and rural communities of practice.
AB  - OBJECTIVE: All senior medical students at the University of Wollongong undertake
      a longitudinal integrated community-based clerkship, supervised by experienced
      general practitioners in a regional or rural community. This study investigates
      the influence of the longitudinal integrated clerkship model of medical education
      on scholarship among preceptors in these practice communities. DESIGN: General
      practitioner preceptors were interviewed after the first student cohort had
      completed their 38-week placements. Analysis of transcripts identified themes
      supporting clinical scholarship among preceptors. The entire transcript for each
      preceptor was analysed, permitting a quantitative determination of each theme.
      Quotations supporting the themes were selected. SETTING: The setting was the
      primary health care practices supervising the longitudinal integrated clerkship
      medical students. PARTICIPANTS: Twenty-six preceptors who supervised longitudinal
      integrated clerkship medical students in rural and regional New South Wales
      participated. None had previously been involved in this model of medical
      education. MAIN OUTCOME MEASURE: The study looked for evidence of clinical
      scholarship among preceptors supervising students in the longitudinal medical
      student clerkship. RESULTS: Thematic analysis of interview transcripts revealed
      evidence of clinical scholarship in regional/rural clinical medicine. The
      'practice' was validated as a place where scholarship occurs, an 'academy of
      learning' and part of the university. About half of the preceptors believed the
      longitudinal integrated clerkship gave students a deeper link with the community.
      Two thirds of participants perceived an improved quality of care in their
      practice. CONCLUSION: Longitudinal integrated clerkships in teaching communities
      of practice provide the opportunity for emergence of clinical scholarship among
      preceptors supporting the learning needs of medical students.

PMID- 24731206
TI  - Is it time for an advanced rural dentist?

PMID- 24731207
TI  - Too many questions.

PMID- 24731208
TI  - Complications after artificial urinary sphincter implantation in patients with or
      without prior radiotherapy.
AB  - OBJECTIVE: To compare complications after implantation of an artificial urinary
      sphincter (AUS) in patients with or without prior radiotherapy (RT). PATIENTS AND
      METHODS: Between January 2000 and December 2011, 160 patients underwent AMS 800
      AUS implantation in our institution. We excluded neurological and traumatic
      causes, implantation on ileal conduit diversion, penoscrotal urethral cuff
      position and those lost to follow-up. In all, 122 patients were included in the
      study, 61 with prior RT and 61 without prior RT. All patients underwent the same
      surgical technique by two different surgeons. All AUS were implanted with a
      bulbar urethral cuff position. The mean (range) follow-up was 37.25 (1-126)
      months. RESULTS: In the patients without prior RT and those with prior RT,
      revision rates were 32.8% vs 29.5%, respectively (P = 0.59). The median time to
      first revision was 11.7 months. Early complications were similar in the two
      groups (4.9% vs 6.5%, P = 1). Erosion rates were not significantly different
      (4.9% vs 13.1%, P = 0.13). However, infection and explantation were more
      prevalent in patients with prior RT [two (3.2%) vs 10 (16.3%), P = 0.018 and
      three (4.9%) vs 12 (19.6%), P = 0.016, respectively]. Finally, continence rates
      were not significantly different [75.4% (without prior RT) vs 63.9% (with prior
      RT), P = 0.23]. CONCLUSION: AUS is the 'gold standard' treatment of male urinary
      incontinence after re-education failure in patients with or without prior RT. Our
      experience showed similar functional outcomes in both groups but a higher rate of
      major complications in the group with prior RT.

PMID- 24731210
TI  - Perinatal mortality by birthweight centile.
AB  - BACKGROUND: Detection of abnormal fetal growth is vital to antenatal care, and
      traditionally birthweights that are <10th or >90th centile are classified as
      small or large for gestational age (LGA). Evidence regarding outcomes for
      birthweight centiles outside these extremes remains unclear. AIMS: To evaluate
      the relationship between birthweight centile and perinatal death and determine
      the 'optimum' birthweight centile with the lowest rate of perinatal mortality.
      METHOD: Data on all Victorian births from 1999 to 2008 were stratified into
      smaller subsets than the traditional small for gestational age (SGA) (<10th
      centile), appropriate for gestational age (AGA) (10-90th centile) and LGA (>90th
      centile) and analysed by all gestations, for term births alone, and using the
      'fetus at risk' approach. Multiple logistic regression was used to adjust for
      age, parity and co-morbidities. RESULTS: For term births, the 'optimum'
      birthweight centile was the 50-90th range (1.1 perinatal deaths/1000 births).
      Lower birthweight centiles had significantly higher rates of perinatal death -
      even those that would be classified as AGA. Babies with a 10-25th birthweight
      centile had a two-fold increased risk of perinatal death (AOR 2.10, 95% CI 1.6,
      2.7). Even those with a 25-50th birthweight centile had higher perinatal
      mortality rates (AOR 1.58, 95% CI 1.3, 2.0). There was no strong evidence of
      higher perinatal mortality in larger birthweight centiles, except term births
      >99th centile. The 'fetus at risk' analysis showed a rise in perinatal mortality
      after 37 weeks' gestation for all birthweight centiles, particularly for SGA
      babies. CONCLUSION: Babies with a birthweight below the 50th centile are at
      greater risk of perinatal mortality compared with the 'optimum' >=50 to <90th
      centile group.

PMID- 24731211
TI  - Adjuvant chemotherapy after curative resection for gastric cancer: a meta
      analysis.
AB  - OBJECTIVE: The aim of this article is to review up-to-date clinical data
      published in the literature in regard to adjuvant chemotherapy in patients with
      gastric cancer after radical surgical resection. MATERIALS AND METHODS: Medline,
      Embase, PubMed, the Cochrane Library and CBMDisc were searched to identify data
      published regarding this issue from 1966 to 2013. All the calculations and
      statistical tests were done using RevMan5.2 software. RESULTS: A total of 29
      trials with 8580 patients met all inclusion criteria. Among them, 27 studies
      reported survival rates at the end of follow-ups, 64.2% alive among 3981 patients
      in the adjuvant chemotherapy arm and 57.3% alive among 4027 patients in the
      observation arm. Statistical results showed that the observation arm had a
      shorter disease-free survival (RR: 1.11, 95% CI: 1.07-1.15), and the treatment
      arm had a lower recurrence rate (RR: 0.79, 95% CI: 0.74-0.84). Leucopenia,
      anemia, nausea and vomiting, diarrhea, alopecia and infection occurred more
      frequently in the treatment arm. Adjuvant chemotherapy decreased the occurrence
      of peritoneum relapse [RR = 0.77, 95% CI (0.66-0.90)], lymphoid nodes relapse [RR
      = 0.58, 95% CI (0.45-0.75)] and local relapse [RR = 0.57, 95% CI (0.41-0.80)].
      CONCLUSIONS: Adjuvant chemotherapy can improve the survival rate and disease-free
      survival rate and reduce the relapse rate after curative resection. Adjuvant
      chemotherapy cannot induce thrombocytopenia and mucositis or affect liver
      function. The tumor in situ recurrence and peritoneum, lymph nodes relapse
      decrease after chemotherapy, and patients benefit from adjuvant chemotherapy
      regardless of the numbers of positive lymph node, depth of local invasion, Asian
      or non-Asian, the length of follow-up, and numbers of cycles.

PMID- 24731212
TI  - Effective technologies for noninvasive remote monitoring in heart failure.
AB  - BACKGROUND: Trials of new technologies to remotely monitor for signs and symptoms
      of worsening heart failure are continually emerging. The extent to which
      technological differences impact the effectiveness of noninvasive remote
      monitoring for heart failure management is unknown. This study examined the
      effect of specific technology used for noninvasive remote monitoring of people
      with heart failure on all-cause mortality and heart failure-related
      hospitalizations. MATERIALS AND METHODS: A subanalysis of a large systematic
      review and meta-analysis was conducted. Studies were stratified according to the
      specific type of technology used, and separate meta-analyses were performed. Four
      different types of noninvasive remote monitoring technologies were identified,
      including structured telephone calls, videophone, interactive voice response
      devices, and telemonitoring. RESULTS: Only structured telephone calls and
      telemonitoring were effective in reducing the risk of all-cause mortality
      (relative risk [RR]=0.87; 95% confidence interval [CI], 0.75-1.01; p=0.06; and
      RR=0.62; 95% CI, 0.50-0.77; p<0.0001, respectively) and heart failure-related
      hospitalizations (RR=0.77; 95% CI, 0.68-0.87; p<0.001; and RR=0.75; 95% CI, 0.63
      0.91; p=0.003, respectively). More research data are required for videophone and
      interactive voice response technologies. CONCLUSIONS: This subanalysis identified
      that only two of the four specific technologies used for noninvasive remote
      monitoring in heart failure improved outcomes. When results of studies that
      involved these disparate technologies were combined in previous meta-analyses,
      significant improvements in outcomes were identified. As such, this study has
      highlighted implications for future meta-analyses of randomized controlled trials
      focused on evaluating the effectiveness of remote monitoring in heart failure.

PMID- 24731213
TI  - Double mutation of cell wall proteins CspB and PBP1a increases secretion of the
      antibody Fab fragment from Corynebacterium glutamicum.
AB  - BACKGROUND: Among other advantages, recombinant antibody-binding fragments (Fabs)
      hold great clinical and commercial potential, owing to their efficient tissue
      penetration compared to that of full-length IgGs. Although production of
      recombinant Fab using microbial expression systems has been reported, yields of
      active Fab have not been satisfactory. We recently developed the Corynebacterium
      glutamicum protein expression system (CORYNEX(r)) and demonstrated improved yield
      and purity for some applications, although the system has not been applied to Fab
      production. RESULTS: The Fab fragment of human anti-HER2 was successfully
      secreted by the CORYNEX(r) system using the conventional C. glutamicum strain
      YDK010, but the productivity was very low. To improve the secretion efficiency,
      we investigated the effects of deleting cell wall-related genes. Fab secretion
      was increased 5.2 times by deletion of pbp1a, encoding one of the penicillin
      binding proteins (PBP1a), mediating cell wall peptidoglycan (PG) synthesis.
      However, this Deltapbp1a mutation did not improve Fab secretion in the wild-type
      ATCC13869 strain. Because YDK010 carries a mutation in the cspB gene encoding a
      surface (S)-layer protein, we evaluated the effect of DeltacspB mutation on Fab
      secretion from ATCC13869. The Deltapbp1a mutation showed a positive effect on Fab
      secretion only in combination with the DeltacspB mutation. The
      DeltacspBDeltapbp1a double mutant showed much greater sensitivity to lysozyme
      than either single mutant or the wild-type strain, suggesting that these
      mutations reduced cell wall resistance to protein secretion. CONCLUSION: There
      are at least two crucial permeability barriers to Fab secretion in the cell
      surface structure of C. glutamicum, the PG layer, and the S-layer. The
      DeltacspBDeltapbp1a double mutant allows efficient Fab production using the
      CORYNEX(r) system.

PMID- 24731214
TI  - Conformational transition of response regulator RR468 in a two-component system
      signal transduction process.
AB  - Signal transduction can be accomplished via a two-component system (TCS)
      consisting of a histidine kinase (HK) and a response regulator (RR). In this
      work, we simulate the response regulator RR468 from Thermotoga maritima, in which
      phosphorylation and dephosphorylation of a conserved aspartate residue acts as a
      switch via a large conformational change concentrated in three proximal loops. A
      detailed view of the conformational transition is obscured by the lack of
      stability of the intermediate states, which are difficult to detect using common
      structural biology techniques. Molecular dynamics (MD) trajectories of the
      inactive and active conformations were run, and show that the inactive (or
      active) trajectories do not exhibit sampling of the active (or inactive)
      conformations on this time scale. Targeted MD (TMD) was used to generate
      trajectories that span the inactive and active conformations and provide a view
      of how a localized event like phosphorylation can lead to conformational changes
      elsewhere in the protein, especially in the three proximal loops. The TMD
      trajectories are clustered to identify stages along the transition path. Residue
      interaction networks are identified that point to key residues having to
      rearrange in the process of transition. These are identified using both hydrogen
      bond analysis and residue interaction strength measurements. Potentials of mean
      force are generated for key residue rearrangements to ascertain their free energy
      barriers. We introduce methods that attempt to extrapolate from one conformation
      to the other and find that the most fluctuating proximal loop can transit part
      way from one to the other, suggesting that this conformational information is
      embedded in the sequence. 

PMID- 24731209
TI  - Circadian rhythms and addiction: mechanistic insights and future directions.
AB  - Circadian rhythms are prominent in many physiological and behavioral functions.
      Circadian disruptions either by environmental or molecular perturbation can have
      profound health consequences, including the development and progression of
      addiction. Both animal and humans studies indicate extensive bidirectional
      relationships between the circadian system and drugs of abuse. Addicted
      individuals display disrupted rhythms, and chronic disruption or particular
      chronotypes may increase the risk for substance abuse and relapse. Moreover,
      polymorphisms in circadian genes and an evening chronotype have been linked to
      mood and addiction disorders, and recent efforts suggest an association with the
      function of reward neurocircuitry. Animal studies are beginning to determine how
      altered circadian gene function results in drug-induced neuroplasticity and
      behaviors. Many studies suggest a critical role for circadian rhythms in reward
      related pathways in the brain and indicate that drugs of abuse directly affect
      the central circadian pacemaker. In this review, we highlight key findings
      demonstrating the importance of circadian rhythms in addiction and how future
      studies will reveal important mechanistic insights into the involvement of
      circadian rhythms in drug addiction.

PMID- 24731215
TI  - Hexagon wreaths: self-assembly of discrete supramolecular fractal architectures
      using multitopic terpyridine ligands.
AB  - In this study, we overcame a challenge in conventional self-assembly of
      macrocycles that uses ditopic 2,2':6',2"-terpyridine (tpy) building blocks with a
      120 degrees  angle between two ligating moieties, which generally produces a
      mixture of multiple macrocycles instead of a single hexagon. Two supramolecular
      hexagon wreaths, [Zn9LA6] and [Zn12LB6], were designed and self-assembled from
      tritopic and tetratopic tpy ligands with Zn(II) ions, respectively. These
      multitopic ligands, bearing multiple binding sites, increased the total density
      of coordination sites and provided high geometric constraints to induce the
      formation of discrete structures. Such hexagon wreaths, which were constructed by
      simple recursion of small hexagons around a central hexagon, exhibit fractal
      geometry features with self-similarity at different levels. The shapes, sizes,
      and structures were fully characterized by NMR, ESI-MS, traveling-wave ion
      mobility mass spectrometry (TWIM-MS), and transmission electron microscopy. With
      diameters around 5.5 nm for [Zn9LA6] and 5.8 nm for [Zn12LB6], the remarkable
      rigidity of these fractal architectures was supported by TWIM-MS, in contrast to
      the high flexibility of macrocycles assembled by ditopic tpy ligands. 

PMID- 24731216
TI  - A feasibility study of low-income homebound older adults' participation in an
      online chronic disease self-management program.
AB  - This study explored the feasibility of "Better Choices, Better Health" (BCBH),
      the online version of Stanford's Chronic Disease Self-Management Program, among
      10 low-income homebound older adults with no or limited computer skills, compared
      with 10 peers with high computer skills. Computer training was provided before
      and at the beginning of the BCBH workshop. Feasibility data consisted of field
      notes by a research assistant who provided computer training, participants'
      weekly logs, and a semi-structured interview with each participant at 4 weeks
      after the completion of BCBH. All those who initially lacked computer skills were
      able to participate in BCBH with a few hours of face-to-face demonstration and
      training. The 4-week postintervention follow-up showed significant improvement in
      health and self-management outcomes. Aging-service agencies need to introduce
      BCBH to low-income homebound older adults and utilize their volunteer base to
      provide computer and Internet skills training for low-income homebound older
      adults in need of such training. 

PMID- 24731217
TI  - Corrigendum.

PMID- 24731218
TI  - Nanostructured bacterial cellulose-poly(4-styrene sulfonic acid) composite
      membranes with high storage modulus and protonic conductivity.
AB  - The present study reports the development of a new generation of bio-based
      nanocomposite proton exchange membranes based on bacterial cellulose (BC) and
      poly(4-styrene sulfonic acid) (PSSA), produced by in situ free radical
      polymerization of sodium 4-styrenesulfonate using poly(ethylene glycol)
      diacrylate (PEGDA) as cross-linker, followed by conversion of the ensuing polymer
      into the acidic form. The BC nanofibrilar network endows the composite membranes
      with excellent mechanical properties at least up to 140  degrees C, a temperature
      where either pure PSSA or Nafion are soft, as shown by dynamic mechanical
      analysis. The large concentration of sulfonic acid groups in PSSA is responsible
      for the high ionic exchange capacity of the composite membranes, reaching 2.25
      mmol g(-1) for a composite with 83 wt % PSSA/PEGDA. The through-plane protonic
      conductivity of the best membrane is in excess of 0.1 S cm(-1) at 94  degrees C
      and 98% relative humidity (RH), decreasing to 0.042 S cm(-1) at 60% RH. These
      values are comparable or even higher than those of ionomers such as Nafion or
      polyelectrolytes such as PSSA. This combination of electric and viscoelastic
      properties with low cost underlines the potential of these nanocomposites as a
      bio-based alternative to other polymer membranes for application in fuel cells,
      redox flow batteries, or other devices requiring functional proton conducting
      elements, such as sensors and actuators. 

PMID- 24731219
TI  - A global quality control system to check PT-INR portable monitor for Antivitamin
      K antagonists.
AB  - INTRODUCTION: Although most guidelines for quality assessment of INR PMs
      recommend specific procedures, no clear regulation or methodology is required for
      outpatients in our country. We have developed a specific INR portable monitor
      (PM) quality control system within our telemedicine organization to check over
      time quality performances and plan corrective actions. METHODS: Based on current
      guidelines for laboratory QC, the following aspects were assessed: suitability of
      PM, defined in terms of imprecision and accuracy; intra-assay imprecision,
      defined according to monthly revision of Levey-Jennings cards with data from each
      peripheral healthcare unit (PHU), using an internal QC provided by the
      manufacturer (CV +/- 20% considered as acceptable); quarterly accuracy study, for
      assessing agreement between analytical instruments, based on duplicate analysis
      of three samples with INR values reflecting different therapeutic ranges
      (differences +/- 0.5 considered as acceptable); external quality assessment
      (NEQAS). RESULTS: In the nine PHU, 18 portable monitors were used to perform 22
      929 test during year 2010. Analytical imprecision was low, showing CVs always
      <5%. Accuracy check showed two of 216 results out of range (0.92%), thus
      providing timely indication for instrument replacement. The external QC NEQAS
      showed optimal performance. CONCLUSION: The current protocol for INR PMs quality
      assessment was effective to establish and maintain a reliable control of devices,
      ensuring the quality of analytical data over time. National authorities should be
      prompted to guarantee and apply correct protocols for INR-PM use.

PMID- 24731220
TI  - Feasibility and impact of an intensified antibiotic stewardship programme
      targeting cephalosporin and fluoroquinolone use in a tertiary care university
      medical center.
AB  - BACKGROUND: Restricted use of third-generation cephalosporins and
      fluoroquinolones has been linked to a reduced incidence of hospital-acquired
      infections with multidrug-resistant bacteria. We implemented an intensified
      antibiotic stewardship (ABS) programme in the medical service of a university
      hospital center aiming at a reduction by at least 30% in the use of these two
      drug classes. METHODS: The ABS programme was focused on the 300-bed medical
      service. Prescription of third-generation cephalosporins was discouraged, whereas
      the use of penicillins was encouraged. Monthly drug use density was measured in
      WHO-ATC defined and locally recommended daily doses (DDD and RDD) per 100 patient
      days, to evaluate trends before (01/2008 to 10/2011) and after starting the
      intervention (1/2012 to 3/2013). The effect was analysed using interrupted time
      series analysis with six non-intervention departments as controls. RESULTS:
      Following initiation of the ABS intervention, overall antibiotic use in the
      medical service declined (p < 0.001). There was a significant intervention
      related decrease in the use of cephalosporins and fluoroquinolones (p < 0.001)
      outperforming the decreasing baseline trend. Trend changes observed in some of
      the control departments were smaller, and the difference between trend changes in
      the medical service and those in control departments were highly significant for
      overall use and cephalosporin use reductions (p < 0.001) as well as for the
      increasing use of penicillins (p < 0.001). Mean use density levels (in RDD per
      100 patient days) dropped for cephalosporins from 16.3 to 10.3 (-37%) and for
      fluoroquinolones from 17.7 to 10.1 (-43%), respectively. During the same period,
      the use of penicillins increased (15.4 to 18.2; 18%). The changes in expenditures
      for antibiotics in the medical service compared to control services minus
      programme costs indicated initial net cost savings likely to be associated with
      the programme. CONCLUSION: An intensified ABS programme targeting cephalosporin
      und fluoroquinolone use in the setting of a large academic hospital is feasible
      and effective. The intervention may serve as a model for other services and
      hospitals with a similar structure and baseline situation.

PMID- 24731222
TI  - Correction: Carnitine supplementation to obese Zucker rats prevents obesity
      induced type I to type II muscle fiber transition and favors an oxidative
      phenotype of skeletal muscle.

PMID- 24731221
TI  - Role of Fbxw7 expression in hepatocellular carcinoma and adjacent non-tumor liver
      tissue.
AB  - BACKGROUND AND AIM: Fbxw7 is a tumor suppressor gene through ubiquitination and
      degradation of multiple oncoproteins. Loss of Fbxw7 expression is frequently
      observed in various human cancers. In the present study, we examined the role of
      Fbxw7 expression in both non-tumor liver tissues and tumor tissues on
      clinicopathological significance. METHODS: Sixty-six patients with hepatocellular
      carcinoma (HCC), who underwent hepatectomy, were divided into two groups: high
      and low gene-expression group, based on the Fbxw7 expression level. We compared
      the clinicopathological factors between the high expression and low expression
      groups in both tumor and non-tumor tissues. RESULTS: Fbxw7 messenger RNA
      expression level in the non-tumor tissues was significantly higher than that in
      the tumor tissues. In the analysis of Fbxw7 expression in tumor and non-tumor
      tissues, disease-free survival rate in the Fbxw7 high expression group was
      significantly higher than that in the low expression group. In multivariable
      analysis, Fbxw7 low expression in both tumor and non-tumor tissue was detected as
      the strongest independent risk factor for HCC recurrence. CONCLUSIONS: Low Fbxw7
      expression in both tumor and non-tumor tissue may be an independent prognostic
      factor for tumor recurrence after hepatectomy in patients with HCC.

PMID- 24731224
TI  - Excretion pattern of enrofloxacin after oral treatment of chicken broilers.
AB  - The metabolism and excretion of enrofloxacin were studied when applied as oral
      solution to chicken broilers for five consecutive days. Sixty 9-day-old broilers
      were isolated within an intensively rearing poultry farm during enrofloxacin
      therapy (15.5 mg/kg per day). The excreta of the isolated broilers were collected
      daily, 9 days after therapy termination, for 13 consecutive days, and analyzed
      for the presence of enrofloxacin and its metabolites [ciprofloxacin, desethylene
      enrofloxacin (DES-EF) and desethylene-ciprofloxacin (DES-CF)]. Enrofloxacin was
      excreted predominantly in the form of the parent compound between days 1 and 13.
      Ciprofloxacin was detected in the excreta between days 1 and 6, whereas minor
      amounts of DES-EF and DES-CF were excreted only between days 1-7 and 1-6,
      respectively. In conclusion, the analysis of the excreta showed that
      approximately 74% of orally applied enrofloxacin was excreted as the parent
      compound, approximately 25% as the main metabolite ciprofloxacin, and
      approximately 1% as the minor metabolites desethylene-enrofloxacin and
      desethylene-ciprofloxacin. 

PMID- 24731225
TI  - The secret behind non-antigen-pulsed autologous dendritic cell therapy in
      transplantation.

PMID- 24731223
TI  - Oxidative dehydrogenative couplings of pyrazol-5-amines selectively forming
      azopyrroles.
AB  - New oxidative dehydrogenative couplings of pyrazol-5-amines for the selective
      synthesis of azopyrrole derivatives have been described. The former reaction
      simultaneously installs C-I and N-N bonds through iodination and oxidation,
      whereas the latter involved a copper-catalyzed oxidative coupling process. The
      resulting iodo-substituted azopyrroles were employed by treatment with various
      terminal alkynes through Sonogashira cross-coupling leading to new azo compounds.

PMID- 24731226
TI  - Protocol for the implementation and evaluation of a community-based intervention
      seeking to reduce dietary salt intake in Lithgow, Australia.
AB  - BACKGROUND: Excess dietary salt is a leading risk for health. Multiple health,
      government, industry and community organisations have identified the need to
      reduce consumption of dietary salt. This project seeks to implement and evaluate
      a community-based salt reduction intervention. METHODS: The study comprises a
      baseline assessment followed by a targeted intervention and then an evaluation of
      efficacy. The study location is Lithgow, a regional town in New South Wales,
      Australia. The salt reduction intervention is based upon the Communication for
      Behavioural Impact framework which utilises an integrated communication model to
      enact community advocacy and impact by providing tools that enable the
      translation of knowledge into behavioural change. The duration of the
      intervention will be between 6 and 12 months. The primary evaluation will be
      through measurement of 24-hr urinary sodium excretion in independent population
      samples aged>20 years, drawn before and after the intervention period. The study
      is designed to detect a difference in mean sodium excretion of 0.7 grams per day
      or greater with 80% power and p=0.05. DISCUSSION: This study will provide a
      robust evaluation of the effectiveness of a community-based intervention seeking
      to reduce dietary salt intake using the Communication for Behavioural Impact
      framework. The results will provide important new evidence to inform the design
      and implementation of current and future salt reduction policies in Australia.
      The results will also have important international implications because,
      following the recent World Health Organization recommendations for the control of
      non-communicable diseases, many countries are now seeking to achieve a reduction
      in average population salt consumption. TRIAL REGISTRATION: ClinicalTrials.gov,
      NCT02105727.

PMID- 24731227
TI  - Association between excess body weight and urine protein concentration in healthy
      dogs.
AB  - BACKGROUND: Markedly overweight people can develop progressive proteinuria and
      kidney failure secondary to obesity-related glomerulopathy (ORG). Glomerular
      lesions in dogs with experimentally induced obesity are similar to those in
      people with ORG. OBJECTIVES: The aim of this study was to evaluate if urine
      protein and albumin excretion is greater in overweight and obese dogs than in
      dogs of ideal body condition. METHODS: Client-owned dogs were screened for
      underlying health conditions. These dogs were assigned a body condition score
      (BCS) using a 9-point scoring system. Dogs with a BCS of >= 6 were classified as
      being overweight/obese, and dogs with a BCS of 4 or 5 were classified as being of
      ideal body weight. The urine protein:creatinine ratio (UPC) and urine
      albumin:creatinine ratio (UAC) were then determined, and compared between 20
      overweight/obese dogs and 22 ideal body weight control dogs. RESULTS: Median UPC
      (0.04 [range, 0.01-0.14; interquartile range, 0.07]) and UAC (0.41 [0-10.39;
      3.21]) of overweight/obese dogs were not significantly different from median UPC
      (0.04 [0.01-0.32; 0.07]) and UAC (0.18 [0-7.04; 1.75]) in ideal body weight dogs.
      CONCLUSIONS: Clinicopathologic abnormalities consistent with ORG were absent from
      overweight/obese dogs in this study.

PMID- 24731228
TI  - Adverse moisture events predict seasonal abundance of Lyme disease vector ticks
      (Ixodes scapularis).
AB  - BACKGROUND: Lyme borreliosis (LB) is the most commonly reported vector-borne
      disease in north temperate regions worldwide, affecting an estimated 300,000
      people annually in the United States alone. The incidence of LB is correlated
      with human exposure to its vector, the blacklegged tick (Ixodes scapularis). To
      date, attempts to model tick encounter risk based on environmental parameters
      have been equivocal. Previous studies have not considered (1) the differences
      between relative humidity (RH) in leaf litter and at weather stations, (2) the RH
      threshold that affects nymphal blacklegged tick survival, and (3) the time
      required below the threshold to induce mortality. We clarify the association
      between environmental moisture and tick survival by presenting a significant
      relationship between the total number of tick adverse moisture events (TAMEs -
      calculated as microclimatic periods below a RH threshold) and tick abundance each
      year. METHODS: We used a 14-year continuous statewide tick surveillance database
      and corresponding weather data from Rhode Island (RI), USA, to assess the effects
      of TAMEs on nymphal populations of I. scapularis. These TAMEs were defined as
      extended periods of time (>8 h below 82% RH in leaf litter). We fit a sigmoid
      curve comparing weather station data to those collected by loggers placed in tick
      habitats to estimate RH experienced by nymphal ticks, and compiled the number of
      historical TAMEs during the 14-year record. RESULTS: The total number of TAMEs in
      June of each year was negatively related to total seasonal nymphal tick
      densities, suggesting that sub-threshold humidity episodes >8 h in duration
      naturally lowered nymphal blacklegged tick abundance. Furthermore, TAMEs were
      positively related to the ratio of tick abundance early in the season when
      compared to late season, suggesting that lower than average tick abundance for a
      given year resulted from tick mortality and not from other factors. CONCLUSIONS:
      Our results clarify the mechanism by which environmental moisture affects
      blacklegged tick populations, and offers the possibility to more accurately
      predict tick abundance and human LB incidence. We describe a method to forecast
      LB risk in endemic regions and identify the predictive role of microclimatic
      moisture conditions on tick encounter risk.

PMID- 24731229
TI  - Efficiency of oestrous synchronization by GnRH, prostaglandins and socio-sexual
      cues in the North African Maure goats.
AB  - This study aims to develop at different seasons, for local North African Maure
      goats, synchronizing protocols simultaneously to the standard 'S' protocol using
      progestagens in association with prostaglandins and gonadotropin. In late May, 40
      goats were assigned to either the 'S' protocol or to a protocol where oestrus and
      ovulation were induced by the buck effect in single-injection progesterone
      treated goats and provoking early luteolysis using prostaglandin 9 days after
      exposure to bucks 'B'. During the 72 h after the treatments ended, 15 and 5 goats
      expressed oestrus in the 'S' and 'B' protocols (p < 0.01). Mean time to oestrus
      was shorter for 'S' than for 'B' goats. Ovulation rate averaged 2.1 +/- 0.22 and
      1.60 +/- 0.35 for, respectively, 'S' and 'B' goats (p > 0.05). During mid
      September, 60 goats were assigned to either 'S' treatment, 'PGF' treatment where
      oestrus and ovulation were synchronized using two injections of prostaglandin 11
      days apart or to 'GnRH' treatment where the goats had their oestrus and ovulation
      synchronized with a GnRH (day 0)-prostaglandin (day 6)-GnRH (day 9) sequence.
      More 'S' goats were detected in oestrus over the 96-h period after the end of the
      treatments (88.8, 73.7 and 55% in 'S', 'PGF' and 'GnRH' treatments, respectively;
      p < 0.05). Mean ovulation rates were 2.3 +/- 0.27, 1.33 +/- 0.27 and 1.33 +/-
      0.27 for, respectively, 'S', 'PGF' and 'GnRH' goats (p < 0.001). Despite a
      similar ovulatory response to 'S' protocol, efficiency of prostaglandin and GnRH
      based treatments should be tested in mid-breeding season. 

PMID- 24731230
TI  - Characterization of oxidative carbonylation on recombinant monoclonal antibodies.
AB  - In the biotechnology industry, oxidative carbonylation as a post-translational
      modification of protein pharmaceuticals has not been studied in detail. Using
      Quality by Design (QbD) principles, understanding the impact of oxidative
      carbonylation on product quality of protein pharmaceuticals, particularly from a
      site-specific perspective, is critical. However, comprehensive identification of
      carbonylation sites has so far remained a very difficult analytical challenge for
      the industry. In this paper, we report for the first time the identification of
      specific carbonylation sites on recombinant monoclonal antibodies with a new
      analytical approach via derivatization with Girard's Reagent T (GRT) and
      subsequent peptide mapping with high-resolution mass spectrometry. Enhanced
      ionization efficiency and high quality MS(2) data resulted from GRT
      derivatization were observed as key benefits of this approach, which enabled
      direct identification of carbonylation sites without any fractionation or
      affinity enrichment steps. A simple data filtering process was also incorporated
      to significantly reduce false positive assignments. Sensitivity and efficiency of
      this approach were demonstrated by identification of carbonylation sites on both
      unstressed and oxidized antibody bulk drug substances. The applicability of this
      approach was further demonstrated by identification of 14 common carbonylation
      sites on three highly similar IgG1s. Our approach represents a significant
      improvement to the existing analytical methodologies and facilitates extended
      characterization of oxidative carbonylation on recombinant monoclonal antibodies
      and potentially other protein pharmaceuticals in the biotechnology industry. 

PMID- 24731231
TI  - Endogenous glutamine production in critically ill patients: the effect of
      exogenous glutamine supplementation.
AB  - INTRODUCTION: Glutamine rate of appearance (Ra) may be used as an estimate of
      endogenous glutamine production. Recently a technique employing a bolus injection
      of isotopically labeled glutamine was introduced, with the potential to allow for
      multiple assessments of the glutamine Ra over time in critically ill patients,
      who may not be as metabolically stable as healthy individuals. Here the technique
      was used to evaluate the endogenous glutamine production in critically ill
      patients in the fed state with and without exogenous glutamine supplementation
      intravenously. METHODS: Mechanically ventilated patients (n = 11) in the
      intensive care unit (ICU) were studied on two consecutive days during continuous
      parenteral feeding. To allow the patients to be used as their own controls, they
      were randomized for the reference measurement during basal feeding without
      supplementation, before or after the supplementation period. Glutamine Ra was
      determined by a bolus injection of 13C-glutamine followed by a period of frequent
      sampling to establish the decay-curve for the glutamine tracer. Exogenous
      glutamine supplementation was given by intravenous infusion of a glutamine
      containing dipeptide, L-alanyl-L-glutamine, 0.28 g/kg during 20 hours. RESULTS: A
      14% increase of endogenous glutamine Ra was seen at the end of the intravenous
      supplementation period as compared to the basal measurements (P = 0.009).
      CONCLUSIONS: The bolus injection technique to measure glutamine Ra to estimate
      the endogenous production of glutamine in critically ill patients was
      demonstrated to be useful for repetitive measurements. The hypothesized
      attenuation of endogenous glutamine production during L-alanyl-L-glutamine
      infusion given as a part of full nutrition was not seen.

PMID- 24731232
TI  - Two-year course of generalized anxiety disorder, social anxiety disorder, and
      panic disorder with agoraphobia in a sample of Latino adults.
AB  - OBJECTIVE: It is imperative to study the clinical course of anxiety disorders
      among Latinos, given the implications for culturally sensitive treatment in this
      population. The current study is the first prospective, observational,
      longitudinal study of anxiety disorders among Latinos. METHOD: Data are reported
      on 139 adult Latinos (M age = 34.65 years, SD = 10.98, 70.5% female) diagnosed
      with social anxiety disorder (SAD; n = 86), generalized anxiety disorder (GAD; n
      = 90), or panic disorder with agoraphobia (PDA; n = 62). The participants were
      interviewed with standardized clinical interviews at intake and annually over 2
      years of follow-up. Probabilities of recovery were calculated using standard
      survival analysis methods. RESULTS: The 2-year recovery rates in this study were
      0.07 for SAD, 0.14 for GAD, 0.03 for PDA, and 0.50 for major depressive disorder
      (MDD). Overall functioning, social adjustment, and life satisfaction in this
      sample were poor. CONCLUSIONS: The recovery rates for anxiety disorders in this
      Latino sample were markedly low. Although caution must be used in comparing these
      data with prior longitudinal studies, these recovery rates seem to be much lower
      than in non-Latino White samples. However, the clinical course of MDD in this
      sample was similar to its course among non-Latino Whites, invoking the pressing
      question of whether there is something about the experience of anxiety disorders
      (but not MDD) among Latinos that makes them more impairing and persistent. The
      answer to that question should inform future treatment development for this
      population.

PMID- 24731233
TI  - Examining moderation analyses in propensity score methods: application to
      depression and substance use.
AB  - OBJECTIVE: This study provides guidance on how propensity score methods can be
      combined with moderation analyses (i.e., effect modification) to examine subgroup
      differences in potential causal effects in nonexperimental studies. As a
      motivating example, we focus on how depression may affect subsequent substance
      use differently for men and women. METHOD: Using data from a longitudinal
      community cohort study (N = 952) of urban African Americans with assessments in
      childhood, adolescence, young adulthood, and midlife, we estimate the influence
      of depression by young adulthood on substance use outcomes in midlife, and
      whether that influence varies by gender. We illustrate and compare 5 different
      techniques for estimating subgroup effects using propensity score methods,
      including separate propensity score models and matching for men and women, a
      joint propensity score model for men and women with matching separately and
      together by gender, and a joint male/female propensity score model that includes
      theoretically important gender interactions with matching separately and together
      by gender. RESULTS: Analyses showed that estimating separate models for men and
      women yielded the best balance and, therefore, is a preferred technique when
      subgroup analyses are of interest, at least in this data. RESULTS also showed
      substance use consequences of depression but no significant gender differences.
      CONCLUSIONS: It is critical to prespecify subgroup effects before the estimation
      of propensity scores and to check balance within subgroups regardless of the type
      of propensity score model used. RESULTS also suggest that depression may affect
      multiple substance use outcomes in midlife for both men and women relatively
      equally.

PMID- 24731234
TI  - Juvenile justice girls' depressive symptoms and suicidal ideation 9 years after
      Multidimensional Treatment Foster Care.
AB  - OBJECTIVE: Multidimensional Treatment Foster Care (MTFC) has been found to reduce
      delinquency among girls in juvenile justice through 2-year follow-up. Given that
      such girls are at elevated risk for suicide and depression into adulthood, we
      tested MTFC effects on long-term trajectories of suicidal ideation and depressive
      symptoms. METHOD: Girls (N = 166; mean [SD] age = 15.3 [1.2] years; 68% White)
      with a recent criminal referral who were mandated to out-of-home care were
      enrolled in 2 sequential cohorts. Girls were randomized to receive MTFC (n = 81)
      or group care (GC) treatment as usual (TAU; n = 85); the second MTFC cohort also
      received modules targeting substance use and risky sexual behavior. Depressive
      symptoms and suicidal ideation were assessed repeatedly through early adulthood
      (mean [SD] follow-up = 8.8 [2.9] years). Suicide attempt history was assessed in
      early adulthood. RESULTS: Girls assigned to MTFC showed significantly greater
      decreases in depressive symptoms across the long-term follow-up than GC girls (pi
      = -.86, p < .05). Decreases in suicidal ideation rates were slightly stronger in
      MTFC than in GC as indicated by a marginal main effect (odds ratio [OR] = .92, p
      < .10) and a significant interaction that favored MTFC in the second cohort
      relative to the first (OR = .88, p < .01). There were no significant MTFC effects
      on suicide attempt. CONCLUSIONS: MTFC decreased depressive symptoms and suicidal
      thinking beyond the decreases attributable to time and TAU. Thus, MTFC has
      further impact on girls' lives than originally anticipated.

PMID- 24731235
TI  - PTSD diagnostic validity in Veterans Affairs electronic records of Iraq and
      Afghanistan veterans.
AB  - OBJECTIVE: Administrative planning and policy decisions frequently rely on
      diagnostic data extracted from large electronic databases. However, the accuracy
      of this diagnostic information is uncertain. The present study examined the
      degree to which various diagnoses of posttraumatic stress disorder (PTSD) within
      Department of Veterans Affairs (VA) electronic databases were concordant with
      PTSD diagnostic status determined by standardized diagnostic interview. METHOD:
      We interviewed 1,649 veterans of the Iraq and Afghanistan wars using the PTSD
      Module of the Structured Clinical Interview for DSM-IV (SCID). Participants also
      completed other interview-based and self-report measures of psychopathology and
      provided consent to access their electronic medical records (EMRs). RESULTS:
      Concordance between database diagnosis and SCID diagnosis was 72.3% for current
      PTSD and 79.4% for lifetime PTSD. We observed associations between concordance
      status and combat exposure, PTSD symptom presentation, comorbid anxiety and
      depression, and psychosocial impairment. Veterans with false-negative PTSD
      diagnoses in the EMR were more likely to report lower levels of combat exposure,
      panic, and PTSD avoidance symptoms. Veterans with false-positive PTSD diagnoses
      in the EMR were more likely to report treatment seeking for emotional problems
      and less overall functional impairment. CONCLUSIONS: Although the majority of
      participants were concordant for PTSD status, over 25% of EMR diagnoses differed
      from those obtained in the diagnostic interview, with varying proportions of
      false positives and false negatives. Overall, those individuals with the most and
      least severe symptom presentations in the diagnostic interview were more likely
      to be accurately classified.

PMID- 24731236
TI  - The application of network label propagation to rank biomarkers in genome-wide
      Alzheimer's data.
AB  - BACKGROUND: Ranking and identifying biomarkers that are associated with disease
      from genome-wide measurements holds significant promise for understanding the
      genetic basis of common diseases. The large number of single nucleotide
      polymorphisms (SNPs) in genome-wide studies (GWAS), however, makes this task
      computationally challenging when the ranking is to be done in a multivariate
      fashion. This paper evaluates the performance of a multivariate graph-based
      method called label propagation (LP) that efficiently ranks SNPs in genome-wide
      data. RESULTS: The performance of LP was evaluated on a synthetic dataset and two
      late onset Alzheimer's disease (LOAD) genome-wide datasets, and the performance
      was compared to that of three control methods. The control methods included chi
      squared, which is a commonly used univariate method, as well as a Relief method
      called SWRF and a sparse logistic regression (SLR) method, which are both
      multivariate ranking methods. Performance was measured by evaluating the top
      ranked SNPs in terms of classification performance, reproducibility between the
      two datasets, and prior evidence of being associated with LOAD.On the synthetic
      data LP performed comparably to the control methods. On GWAS data, LP performed
      significantly better than chi squared and SWRF in classification performance in
      the range from 10 to 1000 top-ranked SNPs for both datasets, and not
      significantly different from SLR. LP also had greater ranking reproducibility
      than chi squared, SWRF, and SLR. Among the 25 top-ranked SNPs that were
      identified by LP, there were 14 SNPs in one dataset that had evidence in the
      literature of being associated with LOAD, and 10 SNPs in the other, which was
      higher than for the other methods. CONCLUSION: LP performed considerably better
      in ranking SNPs in two high-dimensional genome-wide datasets when compared to
      three control methods. It had better performance in the evaluation measures we
      used, and is computationally efficient to be applied practically to data from
      genome-wide studies. These results provide support for including LP in the
      methods that are used to rank SNPs in genome-wide datasets.

PMID- 24731237
TI  - Managing animal wellbeing: a preliminary survey of pig farmers.
AB  - OBJECTIVES: To gather information on producers' perceptions and management
      strategies towards the detection, alleviation of pain and management of sick,
      injured and heat-stressed pigs. METHODS: A total of 16 Victorian pig farmers
      completed a face-to-face questionnaire consisting of 9 open and 26 closed
      questions regarding their detection and management of sick, injured and heat
      stressed pigs and their perceptions of pigs' tolerance to pain. RESULTS: We
      identified 15 behavioural and physiological indicators of pain and heat stress.
      Treatment records were kept more often for weaned progeny and lactating sows than
      for piglets and mated sows. Most producers felt that pigs suffered little pain
      from routine husbandry procedures and that pain relief was not warranted in those
      situations. Castration at 10 days of age was the only procedure considered by
      producers to be very painful. There were inconsistencies in approaches to
      treating pigs in three case studies of animals with sickness or injury of varying
      severity. Meloxicam was stated as the most common anti-inflammatory drug used on
      farm. A small proportion of farmers incorrectly identified antibiotics as anti
      inflammatory drugs. All producers had at least one cooling system in place for
      preventing heat stress in pigs. CONCLUSIONS: The farmers in this survey group
      generally relied on behavioural changes in pigs to signal pain and heat stress.
      Although producers kept treatment records and used hospital pens for compromised
      pigs, our results suggest that the monitoring of pigs' recovery could be
      improved. Producers generally have a good understanding of the use of anti
      inflammatory drugs to aid recovery of pigs.

PMID- 24731238
TI  - Assessment of the prophylactic activity and pharmacokinetic profile of oral
      tafenoquine compared to primaquine for inhibition of liver stage malaria
      infections.
AB  - BACKGROUND: As anti-malarial drug resistance escalates, new safe and effective
      medications are necessary to prevent and treat malaria infections. The US Army is
      developing tafenoquine (TQ), an analogue of primaquine (PQ), which is expected to
      be more effective in preventing malaria in deployed military personnel. METHODS:
      To compare the prophylactic efficacy of TQ and PQ, a transgenic Plasmodium
      berghei parasite expressing the bioluminescent reporter protein luciferase was
      utilized to visualize and quantify parasite development in C57BL/6 albino mice
      treated with PQ and TQ in single or multiple regimens using a real-time in vivo
      imaging system (IVIS). As an additional endpoint, blood stage parasitaemia was
      monitored by flow cytometry. Comparative pharmacokinetic (PK) and liver
      distribution studies of oral and intravenous PQ and TQ were also performed.
      RESULTS: Mice treated orally with three doses of TQ at 5 mg/kg three doses of PQ
      at 25 mg/kg demonstrated no bioluminescence liver signal and no blood stage
      parasitaemia was observed suggesting both drugs showed 100% causal activity at
      the doses tested. Single dose oral treatment with 5 mg TQ or 25 mg of PQ,
      however, yielded different results as only TQ treatment resulted in causal
      prophylaxis in P. berghei sporozoite-infected mice. TQ is highly effective for
      causal prophylaxis in mice at a minimal curative single oral dose of 5 mg/kg,
      which is a five-fold improvement in potency versus PQ. PK studies of the two
      drugs administered orally to mice showed that the absolute bioavailability of
      oral TQ was 3.5-fold higher than PQ, and the AUC of oral TQ was 94-fold higher
      than oral PQ. The elimination half-life of oral TQ in mice was 28 times longer
      than PQ, and the liver tissue distribution of TQ revealed an AUC that was 188
      fold higher than PQ. CONCLUSIONS: The increased drug exposure levels and longer
      exposure time of oral TQ in the plasma and livers of mice highlight the lead
      quality attributes that explain the much improved efficacy of TQ when compared to
      PQ.

PMID- 24731239
TI  - A systematic review of clinician and staff views on the acceptability of
      incorporating remote monitoring technology into primary care.
AB  - OBJECTIVE: Remote monitoring technology (RMT) may enhance healthcare quality and
      reduce costs. RMT adoption depends on perceptions of the end-user (e.g.,
      patients, caregivers, healthcare providers). We conducted a systematic review
      exploring the acceptability and feasibility of RMT use in routine adult patient
      care, from the perspectives of primary care clinicians, administrators, and
      clinic staff. MATERIALS AND METHODS: We searched the databases of Medline, IEEE
      Xplore, and Compendex for original articles published from January 1996 through
      February 2013. We manually screened bibliographies of pertinent studies and
      consulted experts to identify English-language studies meeting our inclusion
      criteria. RESULTS: Of 939 citations identified, 15 studies reported in 16
      publications met inclusion criteria. Studies were heterogeneous by country, type
      of RMT used, patient and provider characteristics, and method of implementation
      and evaluation. Clinicians, staff, and administrators generally held positive
      views about RMTs. Concerns emerged regarding clinical relevance of RMT data,
      changing clinical roles and patterns of care (e.g., reduced quality of care from
      fewer patient visits, overtreatment), insufficient staffing or time to monitor
      and discuss RMT data, data incompatibility with a clinic's electronic health
      record (EHR), and unclear legal liability regarding response protocols.
      CONCLUSIONS: This small body of heterogeneous literature suggests that for RMTs
      to be adopted in primary care, researchers and developers must ensure clinical
      relevance, support adequate infrastructure, streamline data transmission into EHR
      systems, attend to changing care patterns and professional roles, and clarify
      response protocols. There is a critical need to engage end-users in the
      development and implementation of RMT.

PMID- 24731240
TI  - Preparation and characterization of magnetic porous carbon microspheres for
      removal of methylene blue by a heterogeneous Fenton reaction.
AB  - High-specific-surface-area magnetic porous carbon microspheres (MPCMSs) were
      fabricated by annealing Fe(2+)-treated porous polystyrene (PS) microspheres,
      which were prepared using a two-step seed emulsion polymerization process. The
      resulting porous microspheres were then sulfonated, and Fe(2+) was loaded by ion
      exchange, followed by annealing at 250  degrees C for 1 h under an ambient
      atmosphere to obtain the PS-250 composite. The MPCMS-500 and MPCMS-800 composites
      were obtained by annealing PS-250 at 500 and 800  degrees C for 1 h,
      respectively. The iron oxide in MPCMS-500 mainly existed in the form of Fe3O4,
      which was concluded by characterization. The MPCMS-500 carbon microspheres were
      used as catalysts in heterogeneous Fenton reactions to remove methylene blue (MB)
      from wastewater with the help of H2O2 and NH2OH. The results indicated that this
      catalytic system has a good performance in terms of removal of MB; it could
      remove 40 mg L(-1) of MB within 40 min. After the reaction, the catalyst was
      conveniently separated from the media within several seconds using an external
      magnetic field, and the catalytic activity was still viable even after 10 removal
      cycles. The good catalytic performance of the composites could be attributed to
      synergy between the functions of the porous carbon support and the Fe3O4
      nanoparticles embedded in the carrier. This work indicates that porous carbon
      spheres provide good support for the development of a highly efficient
      heterogeneous Fenton catalyst useful for environmental pollution cleanup. 

PMID- 24731241
TI  - Pharmacokinetics and bone resorption evaluation of a novel Cathepsin K inhibitor
      (VEL-0230) in healthy adult horses.
AB  - Plasma pharmacokinetic (PK) and bone resorption biomarker [carboxy-terminal cross
      linking telopeptide of type I collagen (CTX-1)] analyses were performed following
      single and multiple oral dose protocols of a Cathepsin K inhibitor (VEL-0230) in
      horses. Outcomes included plasma and urine drug and CTX-1 concentrations. In the
      dose range study, 2, 4, and 8 mg/kg body weight (b.w.) doses were administered in
      a Latin square design to three mares and evaluated for 1 week. Based on the PK
      characteristics of VEL-0230, 4 mg/kg b.w. was selected for the dose interval
      study in which 3.25 days (d) and 7 days dose intervals were evaluated over three
      administrations using four exercising horses in a Latin square design. The 3.25
      days and 7 days dose intervals provided a rapid inhibition of bone resorption
      based on plasma CTX-1. CTX-1 inhibition prior to next dose administration was not
      different from baseline in the 3.25 days and 7 days protocols, and for the first
      3 days but the sustained CTX-1 inhibition in the 7 days protocol along with the
      cost and logistic benefits for weekly administration made the 7 days protocol
      preferable. Weekly administration of VEL-0230 may provide effective inhibition of
      bone resorption in young exercising horses that returns to baseline within 7 days
      after drug withdrawal even after multiple doses.

PMID- 24731242
TI  - The entropic origin of solvent effects on the single bond cZt-tZt isomerization
      rate constant of 1,3,5-cis-hexatriene in alkane and alcohol solvents: a molecular
      dynamics study.
AB  - The single-bond cZt-tZt isomerization rate constants of 1,3,5-cis-hexatriene
      dissolved in a series of explicit alkane (cyclohexane, n-heptane, and
      cycloheptane) and alcohol (methanol, ethanol, and n-propanol) solvents were
      calculated via reactive flux theory, from classical molecular dynamics
      simulations, at different temperatures (275-325 K). We find that the
      isomerization rate constants in alcohol solvents are slower than those in alkane
      solvents, in accord with the observed experimental trend (Harris, D. A.; Orozco,
      M. B.; Sension, R. J. J. Phys. Chem. A 2006, 110, 9325-9333). We also find that
      the same trend is obtained when the transition state theory limit of the reactive
      flux expression for the reaction rate constant is employed. The solvent
      dependence of the reaction rate constant is then traced back to the fundamentally
      different structure of the solvation shell in alcohol and alkane solvents.
      Whereas in alcohol solvents, hexatriene fits inside a rigid cavity formed by the
      hydrogen-bonded network, which is relatively insensitive to conformational
      dynamics, alkane solvents form a cavity around hexatriene that adjusts to the
      conformational state of hexatriene, thereby increasing the entropy of transition
      state configurations relative to reactant configurations and giving rise to
      faster isomerization. 

PMID- 24731243
TI  - Autologous dendritic cells prolong allograft survival through Tmem176b-dependent
      antigen cross-presentation.
AB  - The administration of autologous (recipient-derived) tolerogenic dendritic cells
      (ATDCs) is under clinical evaluation. However, the molecular mechanisms by which
      these cells prolong graft survival in a donor-specific manner is unknown. Here,
      we tested mouse ATDCs for their therapeutic potential in a skin transplantation
      model. ATDC injection in combination with anti-CD3 treatment induced the
      accumulation of CD8(+) CD11c(+) T cells and significantly prolonged allograft
      survival. TMEM176B is an intracellular protein expressed in ATDCs and initially
      identified in allograft tolerance. We show that Tmem176b(-/-) ATDCs completely
      failed to trigger both phenomena but recovered their effect when loaded with
      donor peptides before injection. These results strongly suggested that ATDCs
      require TMEM176B to cross-present antigens in a tolerogenic fashion. In agreement
      with this, Tmem176b(-/-) ATDCs specifically failed to cross-present male antigens
      or ovalbumin to CD8(+) T cells. Finally, we observed that a Tmem176b-dependent
      cation current controls phagosomal pH, a critical parameter in cross
      presentation. Thus, ATDCs require TMEM176B to cross-present donor antigens to
      induce donor-specific CD8(+) CD11c(+) T cells with regulatory properties and
      prolong graft survival. 

PMID- 24731245
TI  - Acid-mediated ring-expansion reaction of N-aryl-2-vinylazetidines: synthesis and
      unanticipated reactivity of tetrahydrobenzazocines.
AB  - The aza-Clasen rearrangement of N-aryl-2-vinylazetidines has been explored. N
      Aryl-2-vinylazetidines were transformed to corresponding tetrahydrobenzazocines
      in good yields. Unexpectedly, the tetrahydrobenzazocine was unstable and readily
      isomerized to vinyltetrahydroquinoline in the presence of acid. The mechanism of
      this ring contraction was studied in detail. 

PMID- 24731244
TI  - Mechanical ventilation drives pneumococcal pneumonia into lung injury and sepsis
      in mice: protection by adrenomedullin.
AB  - INTRODUCTION: Ventilator-induced lung injury (VILI) contributes to morbidity and
      mortality in acute respiratory distress syndrome (ARDS). Particularly pre-injured
      lungs are susceptible to VILI despite protective ventilation. In a previous
      study, the endogenous peptide adrenomedullin (AM) protected murine lungs from
      VILI. We hypothesized that mechanical ventilation (MV) contributes to lung injury
      and sepsis in pneumonia, and that AM may reduce lung injury and multiple organ
      failure in ventilated mice with pneumococcal pneumonia. METHODS: We analyzed in
      mice the impact of MV in established pneumonia on lung injury, inflammation,
      bacterial burden, hemodynamics and extrapulmonary organ injury, and assessed the
      therapeutic potential of AM by starting treatment at intubation. RESULTS: In
      pneumococcal pneumonia, MV increased lung permeability, and worsened lung
      mechanics and oxygenation failure. MV dramatically increased lung and blood
      cytokines but not lung leukocyte counts in pneumonia. MV induced systemic
      leukocytopenia and liver, gut and kidney injury in mice with pneumonia. Lung and
      blood bacterial burden was not affected by MV pneumonia and MV increased lung AM
      expression, whereas receptor activity modifying protein (RAMP) 1-3 expression was
      increased in pneumonia and reduced by MV. Infusion of AM protected against MV
      induced lung injury (66% reduction of pulmonary permeability p < 0.01; prevention
      of pulmonary restriction) and against VILI-induced liver and gut injury in
      pneumonia (91% reduction of AST levels p < 0.05, 96% reduction of alanine
      aminotransaminase (ALT) levels p < 0.05, abrogation of histopathological changes
      and parenchymal apoptosis in liver and gut). CONCLUSIONS: MV paved the way for
      the progression of pneumonia towards ARDS and sepsis by aggravating lung injury
      and systemic hyperinflammation leading to liver, kidney and gut injury. AM may be
      a promising therapeutic option to protect against development of lung injury,
      sepsis and extrapulmonary organ injury in mechanically ventilated individuals
      with severe pneumonia.

PMID- 24731246
TI  - Human adipose tissue-resident monocytes exhibit an endothelial-like phenotype and
      display angiogenic properties.
AB  - INTRODUCTION: Adipose tissue has the unique property of expanding throughout
      adult life, and angiogenesis is required for its growth. However, endothelial
      progenitor cells contribute minimally to neovascularization. Because myeloid
      cells have proven to be angiogenic, and monocytes accumulate in expanding adipose
      tissue, they might contribute to vascularization. METHODS: The stromal vascular
      fraction (SVF) cells from human adipose tissue were magnetically separated
      according to CD45 or CD14 expression. Adipose-derived mesenchymal stromal cells
      (MSCs) were obtained from SVF CD45- cells. CD14+ monocytes were isolated from
      peripheral blood (PB) mononuclear cells and then cultured with SVF-derived MSCs.
      Freshly isolated or cultured cells were characterized with flow cytometry; the
      conditioned media were analyzed for the angiogenic growth factors, angiopoietin-2
      (Ang-2), vascular endothelial growth factor (VEGF), basic fibroblast growth
      factor (bFGF), hepatocyte growth factor (HGF), granulocyte colony-stimulating
      factor (G-CSF), and granulocyte macrophage colony-stimulating factor (GM-CSF)
      with Luminex Technology; their angiogenic capacity was determined in an in vivo
      gelatinous protein mixture (Matrigel) plug angiogenesis assay. RESULTS: CD45+
      hematopoietic cells within the SVF contain CD14+ cells that co-express the CD34
      progenitor marker and the endothelial cell antigens VEGF receptor 2 (VEGFR2/KDR),
      VEGFR1/Flt1, and Tie2. Co-culture experiments showed that SVF-derived MSCs
      promoted the acquisition of KDR and Tie-2 in PB monocytes. MSCs secreted
      significant amounts of Ang-2 and HGF, but minimal amounts of bFGF, G-CSF, or GM
      CSF, whereas the opposite was observed for SVF CD14+ cells. Additionally, SVF
      CD14+ cells secreted significantly higher levels of VEGF and bFGF than did MSCs.
      Culture supernatants of PB monocytes cultured with MSCs contained significantly
      higher concentrations of VEGF, HGF, G-CSF, and GM-CSF than did the supernatants
      from cultures without MSCs. Quantitative analysis of angiogenesis at 14 days
      after implantation demonstrated that neovascularization of the implants
      containing SVF CD14+ cells or PB monocytes previously co-cultured with MSCs was
      3.5 or 2 times higher than that observed in the implants with SVF-derived MSCs.
      Moreover, immunofluorescence of Matrigel sections revealed that SVF CD14+ cells
      differentiated into endothelial cells and contributed to vascular endothelium.
      CONCLUSIONS: The results from this study suggest that adipose tissue-resident
      monocytes should contribute to tissue vascularization. Because SVF CD14+ cells
      were more efficient in inducing angiogenesis than SVF-derived MSCs, and
      differentiated into vascular endothelial cells, they may constitute a new cell
      source for cell-based therapeutic angiogenesis.

PMID- 24731247
TI  - Kinetics of mycolactone in human subcutaneous tissue during antibiotic therapy
      for Mycobacterium ulcerans disease.
AB  - BACKGROUND: Mycobacterium ulcerans (M. ulcerans) causes a devastating necrotising
      infection of skin tissue leading to progressive ulceration. M. ulcerans is the
      only human pathogen that secretes mycolactone, a polyketide molecule with potent
      cytotoxic and immunomodulatory properties. These unique features make mycolactone
      an attractive biomarker for M. ulcerans disease. We sought to measure the
      concentration of mycolactone within lesions of patients with Buruli ulcer before,
      during and after antibiotic treatment to evaluate its association with the
      clinical and bacteriological response to therapy. METHODS: Biopsies of M.
      ulcerans infected skin lesions were obtained from patients before, during and
      after antibiotic therapy. Lipids were extracted from the biopsies and
      concentration of mycolactone was assayed by mass spectrometry and a cytotoxicity
      assay and correlated with clinical and bacteriological response to therapy.
      RESULTS: Baseline concentration of mycolactone measured by mass spectrometry
      predicted time to complete healing of small nodules and ulcers. Even though intra
      lesional concentrations of mycolactone declined with antibiotic treatment, the
      toxin was still present after antibiotic treatment for 6 weeks and also 4 weeks
      after the end of treatment for 8 weeks in a subgroup of patients with slowly
      healing lesions. Additionally viable bacilli were detected in a proportion of
      these slowly healing lesions during and after treatment. CONCLUSIONS: Our
      findings indicate that baseline intra-lesional mycolactone concentration and its
      kinetics with antibiotic therapy are important prognostic determinants of
      clinical and bacteriological response to antibiotic treatment for Mycobacterium
      ulcerans disease. Mycolactone may be a useful biomarker with potential utility in
      optimising antibiotic therapy.

PMID- 24731248
TI  - Using an autologistic regression model to identify spatial risk factors and
      spatial risk patterns of hand, foot and mouth disease (HFMD) in Mainland China.
AB  - BACKGROUND: There have been large-scale outbreaks of hand, foot and mouth disease
      (HFMD) in Mainland China over the last decade. These events varied greatly across
      the country. It is necessary to identify the spatial risk factors and spatial
      distribution patterns of HFMD for public health control and prevention. Climate
      risk factors associated with HFMD occurrence have been recognized. However, few
      studies discussed the socio-economic determinants of HFMD risk at a space scale.
      METHODS: HFMD records in Mainland China in May 2008 were collected. Both climate
      and socio-economic factors were selected as potential risk exposures of HFMD.
      Odds ratio (OR) was used to identify the spatial risk factors. A spatial
      autologistic regression model was employed to get OR values of each exposures and
      model the spatial distribution patterns of HFMD risk. RESULTS: Results showed
      that both climate and socio-economic variables were spatial risk factors for HFMD
      transmission in Mainland China. The statistically significant risk factors are
      monthly average precipitation (OR = 1.4354), monthly average temperature (OR =
      1.379), monthly average wind speed (OR = 1.186), the number of industrial
      enterprises above designated size (OR = 17.699), the population density (OR =
      1.953), and the proportion of student population (OR = 1.286). The spatial
      autologistic regression model has a good goodness of fit (ROC = 0.817) and
      prediction accuracy (Correct ratio = 78.45%) of HFMD occurrence. The autologistic
      regression model also reduces the contribution of the residual term in the
      ordinary logistic regression model significantly, from 17.25 to 1.25 for the odds
      ratio. Based on the prediction results of the spatial model, we obtained a map of
      the probability of HFMD occurrence that shows the spatial distribution pattern
      and local epidemic risk over Mainland China. CONCLUSIONS: The autologistic
      regression model was used to identify spatial risk factors and model spatial risk
      patterns of HFMD. HFMD occurrences were found to be spatially heterogeneous over
      the Mainland China, which is related to both the climate and socio-economic
      variables. The combination of socio-economic and climate exposures can explain
      the HFMD occurrences more comprehensively and objectively than those with only
      climate exposures. The modeled probability of HFMD occurrence at the county level
      reveals not only the spatial trends, but also the local details of epidemic risk,
      even in the regions where there were no HFMD case records.

PMID- 24731249
TI  - Disappointment and adherence among parents of newborns allocated to the control
      group: a qualitative study of a randomized clinical trial.
AB  - BACKGROUND: When a child participates in a clinical trial, informed consent has
      to be given by the parents. Parental motives for participation are complex, but
      the hope of getting a new and better treatment for the child is important. We
      wondered how parents react when their child is allocated to the control group of
      a randomized controlled trial, and how it will affect their future engagement in
      the trial. METHODS: We included parents of newborns randomized to the control arm
      in the Danish Calmette study at Rigshospitalet in Copenhagen. The Calmette study
      is a randomized clinical trial investigating the non-specific effects of early
      BCG-vaccine to healthy neonates. Randomization is performed immediately after
      birth and parents are not blinded to the allocation. We set up a semi-structured
      focus group with six parents from four families. Afterwards we telephone
      interviewed another 19 mothers to achieve saturation. Thematic analysis was used
      to identify themes across the data sets. RESULTS: The parents reported good
      understanding of the randomization process. Their most common reaction to
      allocation was disappointment, though relief was also seen. A model of reactions
      to being allocated to the control group was developed based on the participants'
      different positions along two continuities from 'Our participation in trial is
      not important' to 'Our participation in trial is important', and 'Vaccine not
      important to us' to 'Vaccine important to us'. Four very disappointed families
      had thought of getting the vaccine elsewhere, and one had actually had their
      child vaccinated. All parents involved in the focus group and the telephone
      interviews wanted to participate in the follow-ups planned for the Calmette
      study. CONCLUSIONS: This study identified an almost universal experience of
      disappointment among parents of newborns who were randomized to the control
      group, but also a broad expression of understanding and accepting the idea of
      randomization. The trial staff might use the model of reactions in understanding
      the parents' disappointment and in this way support their motives for
      participation. A generalized version might be applicable across randomized
      controlled trials at large. TRIAL REGISTRATION: The Calmette study is registered
      in EudraCT (https://eudract.ema.europa.eu/) with trial number 2010-021979-85.

PMID- 24731250
TI  - Isolation of neutral mononuclear copper complexes stabilized by two cyclic
      (alkyl)(amino)carbenes.
AB  - Two (cAAC)2Cu complexes, featuring a two-coordinate copper atom in the formal
      oxidation state zero, were prepared by reducing (Et2-cAAC)2Cu(+)I(-) with
      metallic sodium in THF, and by a one-pot synthesis using Me2-cAAC, Cu(II)Cl2, and
      KC8 in toluene in a molar ratio of 2:1:2, respectively. Both complexes are highly
      air and moisture sensitive but can be stored in the solid state for a month at
      room temperature. DFT calculations showed that in these complexes the copper
      center has a d(10) electronic configuration and the unpaired electron is
      delocalized over two carbene carbon atoms. This was further confirmed by the EPR
      spectra, which exhibit multiple hyperfine lines due to the coupling of the
      unpaired electron with (63,65)Cu isotopes, (14)N, and (1)H nuclei. 

PMID- 24731251
TI  - Disease progression among 446 children with newly diagnosed type 1 diabetes
      located in Scandinavia, Europe, and North America during the last 27 yr.
AB  - OBJECTIVE: To clarify whether the rate of decline in stimulated C-peptide (SCP)
      from 2 to 15 months after diagnosis has changed over an interval of 27 yr.
      RESEARCH DESIGN AND METHODS: The rate of decline in SCP levels at 1, 2, 3, 6, 9,
      12, and 15 months after diagnosis was compared in four paediatric cohorts from
      Scandinavian and European countries including 446 children with new onset type 1
      diabetes (T1D, 1982-2004). Findings were evaluated against 78 children (2004
      2009) from the TrialNet studies. RESULTS: The mean rate of decline [%/month (+/
      SEM)] in SCP for a 10-yr-old child was 7.7%/month (+/-1.5) in the 1982-1985
      Cohort, 6.3%/month (+/-1.7) in the 1995-1998 Cohort, 7.8%/month (+/-0.7) in the
      1999-2000 Cohort, and 10.7%/month (+/-0.9) in the latest 2004-2005 Cohort (p =
      0.05). Including the TrialNet Cohort with a rate of decline in SCP of 10.0%/month
      (+/-0.9) the differences between the cohorts are still significant (p = 0.039).
      The rate of decline in SCP was negatively associated with age (p < 0.0001),
      insulin antibodies (IA) (p = 0.003), and glutamic acid decarboxylase-65 (GAD65A)
      (p = 0.03) initially with no statistically significant effect of body mass index
      (BMI) Z-score at 3 months. Also, at 3 months the time around partial remission,
      the effect of age on SCP was significantly greater in children <=5 yr compared
      with older children (p <= 0.0001). CONCLUSIONS: During the past 27 yr, initial C
      peptide as well as the rate of C-peptide decline seem to have increased. The rate
      of decline was affected significantly by age, GAD65A, and IA, but not BMI Z-score
      or initial C-peptide.

PMID- 24731252
TI  - Efficacy of slow-release tags impregnated with aggregation-attachment pheromone
      and deltamethrin for control of Amblyomma variegatum on St. Kitts, West Indies.
AB  - BACKGROUND: Amblyomma variegatum is an important cause of morbidity, mortality
      and economic losses in Africa and the West Indies. Attempts to control and/or
      eradicate the tick from the Caribbean have largely been unsuccessful because of
      difficulties relating to the biology of the three-host tick and problems with
      applying acaricides on a regular basis to free-ranging domestic ruminants. While
      plastic collars impregnated with insecticides are widely and effectively used in
      companion animals to control external parasites there is little information on
      this technology in ruminants. METHODS: Over 21 months we tested the efficacy of
      slow-release plastic tags impregnated with deltamethrin (7%) and aggregation
      attachment pheromones (DPITs) in controlling A. variegatum on free-ranging cattle
      on two farms on St. Kitts. The tags were replaced every three months or when
      found to be lost. RESULTS: On sentinel animals fitted with tags containing only
      aggregation-attachment pheromones there were an average of 23.1 ticks per semi
      monthly visit although this number varied considerably, peaking in the dry season
      around May and being lowest in August to October during the wet season.
      Significantly fewer ticks (3.5 on average) were found on cattle with DPITs at
      each visit (P < 0.001). Although the DIPTs provided good control (92% on
      average), they did not significantly reduce A. variegatum in the environment with
      tick numbers on sentinels being higher in the second year of the study, despite
      up to 44% of animals being fitted with DPITs. The tags were economical, costing
      0.2% of the 1% flumethrin pour-on treatment widely recommended for A. variegatum
      control in the Caribbean. The major problem encountered was that 38% of tail tags
      were lost before they were due for replacement every three months. CONCLUSIONS:
      Our study has shown that DPITs are cheap to produce, easy to place, only require
      handling of animals every three months, and are very effective in protecting
      cattle from A. variegatum. Before DPITs can be considered for eradication
      programs the problems needing to be addressed include loss of tail tags,
      particularly in thick vegetation, and the optimum number of animals that must be
      treated to reduce numbers of ticks in the environment.

PMID- 24731254
TI  - Relationship between crystallization tendencies during cooling from melt and
      isothermal storage: toward a general understanding of physical stability of
      pharmaceutical glasses.
AB  - The lack of protocols to predict the physical stability has been one of the most
      important issues in the use of amorphous solid dispersions. In this paper, the
      crystallization behaviors of pharmaceutical glasses, which have large variations
      in their crystallization tendencies, have been investigated. Although each
      compound appears to have a wide variation in their crystallization time, the
      initiation time for crystallization could be generalized as a function of only
      Tg/T, where Tg and T are the glass transition temperature and storage
      temperature, respectively. All compounds in which crystallization was mainly
      governed by temperature had similar activation energies for crystallization
      initiation, ca. 210-250 kJ/mol, indicating that physical stability at any
      temperature is predictable from only Tg. Increased stability is expected for
      other compounds, where crystallization is inhibited by an large energetic
      barrier, and stochastic nucleation plays an important role in initiating
      crystallization. The difference in the dominant factor, either temperature or
      pressure, appeared to correlate with the nucleation mechanism, and this could be
      determined by a cool-heat cycle after melting using thermal analysis. This
      conclusion should make prediction of physical stability of amorphous formulations
      easier, although the investigation was conducted under ideal conditions, which
      eliminated surface effects.

PMID- 24731253
TI  - Characterization of an autotransporter adhesin protein shared by Burkholderia
      mallei and Burkholderia pseudomallei.
AB  - BACKGROUND: Autotransporters form a large family of outer membrane proteins
      specifying diverse biological traits of Gram-negative bacteria. In this study, we
      report the identification and characterization of a novel autotransporter gene
      product of Burkholderia mallei (locus tag BMA1027 in strain ATCC 23344). RESULTS:
      Database searches identified the gene in at least seven B. mallei isolates and
      the encoded proteins were found to be 84% identical. Inactivation of the gene
      encoding the autotransporter in the genome of strain ATCC 23344 substantially
      reduces adherence to monolayers of HEp-2 laryngeal cells and A549 type II
      pneumocytes, as well as to cultures of normal human bronchial epithelium (NHBE).
      Consistent with these findings, expression of the autotransporter on the surface
      of recombinant E. coli bacteria increases adherence to these cell types by 5-7
      fold. The gene specifying the autotransporter was identified in the genome of 29
      B. pseudomallei isolates and disruption of the gene in strain DD503 reduced
      adherence to NHBE cultures by 61%. Unlike B. mallei, the mutation did not impair
      binding of B. pseudomallei to A549 or HEp-2 cells. Analysis of sera from mice
      infected via the aerosol route with B. mallei and B. pseudomallei revealed that
      animals inoculated with as few as 10 organisms produce antibodies against the
      autotransporter, therefore indicating expression in vivo. CONCLUSIONS: Our data
      demonstrate that we have identified an autotransporter protein common to the
      pathogenic species B. mallei and B. pseudomallei which mediates adherence to
      respiratory epithelial cells and is expressed in vivo during the course of
      aerosol infection.

PMID- 24731255
TI  - Could T cells be involved in lung deterioration and hyperglycemia in cystic
      fibrosis?
AB  - Cystic fibrosis-related diabetes (CFRD) is the most frequent complication of
      cystic fibrosis (CF) and associated with increased mortality. Why patients have
      an accelerated loss of lung function before the diagnosis of CFRD remains poorly
      understood. We reported that patients with or without CFRD had increased glucose
      excursions when compared to healthy peers. Studies have demonstrated that
      patients with CF have increased glucose fluctuations and hyperglycemia and that
      this may affect the clinical course of CF and lead to lymphocyte dysfunction. T
      helper 17 (Th17) lymphocytes produce and secrete the pro-inflammatory cytokine IL
      17. The Th17 pathway is involved in CF lung inflammation, beta-cell destruction
      in type 1 diabetes (T1D) and Th17 cells of patients with type 2 diabetes have
      increased production of IL-17 when compared to healthy peers. Also, regulatory T
      cells (Tregs) have been shown to be dysfunctional and produce IL-17 in T1D.
      Furthermore, vitamin D can affect inflammation in CF, diabetes and the
      differentiation of lymphocytes. In this review, we discuss the potential roles of
      hyperglycemia on Th17 cells, Tregs and IL-17 as a potential cause for accelerated
      lung function decline before CFRD and how this could be modulated by vitamin D or
      by directly intervening in the IL-17A pathway. 

PMID- 24731257
TI  - Role of surface functionality in the electrochemical performance of silicon
      nanowire anodes for rechargeable lithium batteries.
AB  - We report the synthesis of silicon nanowires using the supercritical-fluid-liquid
      solid growth method from two silicon precursors, monophenylsilane and trisilane.
      The nanowires were synthesized at least on a gram scale at a pilot scale
      facility, and various surface modification methods were developed to optimize the
      electrochemical performance. The observed electrochemical performance of the
      silicon nanowires was clearly dependent on the origination of the surface
      functional group, either from the residual precursor or from surface
      modifications. On the basis of detailed electron microscopy, X-ray photoelectron
      spectroscopy, and confocal Raman spectroscopy studies, we analyzed the surface
      chemical reactivity of the silicon nanowires with respect to their
      electrochemical performance in terms of their capacity retention over continuous
      charge-discharge cycles. 

PMID- 24731256
TI  - Anti-malarial activity of indole alkaloids isolated from Aspidosperma olivaceum.
AB  - BACKGROUND: Several species of Aspidosperma (Apocynaceae) are used as treatments
      for human diseases in the tropics. Aspidosperma olivaceum, which is used to treat
      fevers in some regions of Brazil, contains the monoterpenoid indole alkaloids
      (MIAs) aspidoscarpine, uleine, apparicine, and N-methyl-tetrahydrolivacine. Using
      bio-guided fractionation and cytotoxicity testing in a human hepatoma cell line,
      several plant fractions and compounds purified from the bark and leaves of the
      plant were characterized for specific therapeutic activity (and selectivity
      index, SI) in vitro against the blood forms of Plasmodium falciparum. METHODS:
      The activity of A. olivaceum extracts, fractions, and isolated compounds was
      evaluated against chloroquine (CQ)-resistant P. falciparum blood parasites by in
      vitro testing with radiolabelled [3H]-hypoxanthine and a monoclonal anti
      histidine-rich protein (HRPII) antibody. The cytotoxicity of these fractions and
      compounds was evaluated in a human hepatoma cell line using a 3-[4,5
      dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) assay, and the SI
      was calculated as the ratio between the toxicity and activity. Two leaf fractions
      were tested in mice with Plasmodium berghei. RESULTS: All six fractions from the
      bark and leaf extracts were active in vitro at low doses (IC50 < 5.0 MUg/mL)
      using the anti-HRPII test, and only two (the neutral and basic bark fractions)
      were toxic to a human cell line (HepG2). The most promising fractions were the
      crude leaf extract and its basic residue, which had SIs above 50. Among the four
      pure compounds evaluated, aspidoscarpine in the bark and leaf extracts showed the
      highest SI at 56; this compound, therefore, represents a possible anti-malarial
      drug that requires further study. The acidic leaf fraction administered by gavage
      to mice with blood-induced malaria was also active. CONCLUSION: Using a bio
      monitoring approach, it was possible to attribute the anti-P. falciparum activity
      of A. olivaceum to aspidoscarpine and, to a lesser extent, N-methyl
      tetrahydrolivacine; other isolated MIA molecules were active but had lower SIs
      due to their higher toxicities. These results stood in contrast to previous work
      in which the anti-malarial activity of other Aspidosperma species was attributed
      to uleine.

PMID- 24731258
TI  - Comparative plant sphingolipidomic reveals specific lipids in seeds and oil.
AB  - Plant sphingolipids are a highly diverse family of structural and signal lipids.
      Owing to their chemical diversity and complexity, a powerful analytical method
      was required to identify and quantify a large number of individual molecules with
      a high degree of structural accuracy. By using ultra-performance liquid
      chromatography with a single elution system coupled to electrospray ionization
      tandem mass spectrometry (UPLC-ESI-MS/MS) in the positive multiple reaction
      monitoring (MRM) mode, detailed sphingolipid composition was analyzed in various
      tissues of two Brassicaceae species Arabidopsis thaliana and Camelina sativa. A
      total of 300 molecular species were identified defining nine classes of
      sphingolipids, including Cers, hCers, Glcs and GIPCs. High-resolution mass
      spectrometry identified sphingolipids including amino- and N-acylated-GIPCs. The
      comparative analysis of seedling, seed and oil sphingolipids showed tissue
      specific distribution suggesting metabolic channeling and compartmentalization. 

PMID- 24731259
TI  - Stable, water extractable isothiocyanates from Moringa oleifera leaves attenuate
      inflammation in vitro.
AB  - Moringa (Moringa oleifera Lam.) is an edible plant used as both a food and
      medicine throughout the tropics. A moringa concentrate (MC), made by extracting
      fresh leaves with water, utilized naturally occurring myrosinase to convert four
      moringa glucosinolates into moringa isothiocyanates. Optimum conditions
      maximizing MC yield, 4-[(alpha-L-rhamnosyloxy)benzyl]isothiocyanate, and 4-[(4'-O
      acetyl-alpha-L-rhamnosyloxy)benzyl]isothiocyanate content were established (1:5
      fresh leaf weight to water ratio at room temperature). The optimized MC contained
      1.66% isothiocyanates and 3.82% total polyphenols. 4-[(4'-O-acetyl-alpha-L
      rhamnosyloxy)benzyl]isothiocyanate exhibited 80% stability at 37 degrees C for 30
      days. MC, and both of the isothiocyanates described above significantly decreased
      gene expression and production of inflammatory markers in RAW macrophages.
      Specifically, both attenuated expression of iNOS and IL-1beta and production of
      nitric oxide and TNFalpha at 1 and 5 MUM. These results suggest a potential for
      stable and concentrated moringa isothiocyanates, delivered in MC as a food-grade
      product, to alleviate low-grade inflammation associated with chronic diseases.

PMID- 24731260
TI  - A seco-laurane sesquiterpene and related laurane derivatives from the red alga
      Laurencia okamurai Yamada.
AB  - A ring-cleaved sesquiterpene, named seco-laurokamurone, four laurane-type
      sesquiterpenes, laurepoxyene, 3beta-hydroperoxyaplysin, 3alpha-hydroperoxy-3
      epiaplysin, and 8,10-dibromoisoaplysin, one laurokamurane-type sesquiterpene,
      laurokamurene D, and one bisabolane-type sesquiterpene, (5S)-5-acetoxy-beta
      bisabolene, have been isolated from a re-collection of the red alga Laurencia
      okamurai Yamada, together with six other known sesquiterpenes. Their structures,
      including relative configuration, were elucidated by detailed analysis of
      spectroscopic data, and by comparison with data for related known compounds. In
      addition, on the basis of chemical conversions, degradation results, and
      biogenetic considerations, the absolute configurations of several of these
      compounds were also tentatively proposed. seco-Laurokamurone possesses an
      unprecedented carbon skeleton, formed from an oxidative cleavage of the
      laurokamurane skeleton, and laurokamurene D represents the fourth example of a
      laurokamurane-type sesquiterpene from a natural source. The in vitro antifungal
      activity of many of these compounds was evaluated against four fungi
      (Cryptococcus neoformans, Candida glabrata, Trichophyton rubrum, and Aspergillus
      fumigatus), as well as assessing cytotoxicity against HL-60 and A-549 human
      cancer cell lines. The compounds studied displayed moderate activities, relative
      to controls. 

PMID- 24731261
TI  - Multidimensional mapping of spin-exchange optical pumping in clinical-scale batch
      mode 129Xe hyperpolarizers.
AB  - We present a systematic, multiparameter study of Rb/(129)Xe spin-exchange optical
      pumping (SEOP) in the regimes of high xenon pressure and photon flux using a 3D
      printed, clinical-scale stopped-flow hyperpolarizer. In situ NMR detection was
      used to study the dynamics of (129)Xe polarization as a function of SEOP-cell
      operating temperature, photon flux, and xenon partial pressure to maximize
      (129)Xe polarization (PXe). PXe values of 95 +/- 9%, 73 +/- 4%, 60 +/- 2%, 41 +/-
      1%, and 31 +/- 1% at 275, 515, 1000, 1500, and 2000 Torr Xe partial pressure were
      achieved. These PXe polarization values were separately validated by ejecting the
      hyperpolarized (129)Xe gas and performing low-field MRI at 47.5 mT. It is shown
      that PXe in this high-pressure regime can be increased beyond already record
      levels with higher photon flux and better SEOP thermal management, as well as
      optimization of the polarization dynamics, pointing the way to further
      improvements in hyperpolarized (129)Xe production efficiency. 

PMID- 24731262
TI  - Phosphorylation of Bacillus subtilis gene regulator AbrB modulates its DNA
      binding properties.
AB  - AbrB is a global gene regulator involved in transition phase phenomena in
      Bacillus subtilis. It participates in a complex regulatory network governing the
      expression of stationary-phase functions. AbrB was previously found to be
      phosphorylated on serine 86 located close to its C-terminal oligomerization
      domain. Here we report that AbrB can be phosphorylated by three B. subtilis
      serine/threonine kinases expressed during the transition and stationary phase:
      PrkC, PrkD and YabT. Our in vitro findings suggest that AbrB phosphorylation
      impedes its DNA binding and abolishes binding cooperativity. In vivo we
      established that a phospho-mimetic mutation abrB S86D leads to a significant loss
      of AbrB control over several key target functions: exoprotease production,
      competence development and sporulation. A wider transcriptome analysis of abrB
      S86D and S86A mutant strains revealed deregulation of a large number of target
      genes. We therefore propose that AbrB phosphorylation serves as an additional
      input for fine-tuning the activity of this ambiactive gene regulator.

PMID- 24731263
TI  - Second transcatheter aortic valve implantation for treatment of suboptimal
      function of previously implanted prosthesis: review of the literature.
AB  - OBJECTIVES: To systematically review reported cases of second transcatheter
      aortic valve deployment within a previously implanted prosthesis (TAV-in-TAV).
      BACKGROUND: TAV-in-TAV deployment is one of the rescue strategies undertaken due
      to an unsuccessful or suboptimal transcatheter aortic valve implantation (TAVI)
      result. Currently, there are no clear indications for second valve implantation
      and outcomes of patients with 2 prostheses deployed remain poorly known. METHODS:
      The MEDLINE and PubMed databases were searched for cases of TAV-in-TAV
      implantations of aortic valve. RESULTS: Forty-three articles reporting on TAV-in
      TAV deployment were included in the review. The most frequently observed
      indication for second valve implantation was aortic regurgitation (AR) occurring
      shortly after TAVI. There was a strong dominance of paravalvular over
      intravalvular AR, with prosthesis malposition being the main underlying cause of
      TAVI failure (81% of all identified cases). Perioperative echocardiographic
      images are crucial in identifying causes of failure and helpful in optimal rescue
      strategy selection. Success rate of TAV-in-TAV implantation varies from 90% to
      100% with mortality rate of 0-14.3% at 30 days. Despite similar aortic valve
      function in follow-up, TAV-in-TAV may be an independent predictor of increased
      cardiovascular mortality. CONCLUSIONS: TAV-in-TAV implantation is feasible and
      results in favorable short- and mid-term outcomes in patients with acute failure
      of TAVI without recourse to open-heart surgery. Further studies are needed to
      establish algorithm of the management of unsuccessful or suboptimal implantation
      results.

PMID- 24731264
TI  - Optical frequency domain imaging in patients with Barrett's neoplasia: an ex vivo
      case study with correlated endoscopic and histology views.

PMID- 24731265
TI  - Single-balloon-assisted ERCP with electrohydraulic lithotripsy for the treatment
      of a bile duct stone in a patient with a hepaticojejunostomy.

PMID- 24731266
TI  - Refractory gastric antral vascular ectasia treated by a novel through-the-scope
      ablation catheter.

PMID- 24731267
TI  - In vivo diagnosis of clonorchiasis during cholangioscopy for workup of suspected
      cholangiocarcinoma (with video).

PMID- 24731268
TI  - The effect of neoadjuvant chemotherapy on physical fitness and survival in
      patients undergoing oesophagogastric cancer surgery.
AB  - BACKGROUND: Neoadjuvant chemotherapy (NAC) followed by surgery for resectable
      oesophageal or gastric cancer improves outcome when compared with surgery alone.
      However NAC has adverse effects. We assess here whether NAC adversely affects
      physical fitness and whether such an effect is associated with impaired survival
      following surgery. METHODS: We prospectively studied 116 patients with
      oesophageal or gastric cancer to assess the effect of NAC on physical fitness, of
      whom 89 underwent cardiopulmonary exercise testing (CPET) before NAC and
      proceeded to surgery. 39 patients were tested after all cycles of NAC but prior
      to surgery. Physical fitness was assessed by measuring oxygen uptake (VO2 in ml
      kg(-1) min(-1)) at the estimated lactate threshold (thetaL) and at peak exercise
      (VO2 peak in ml kg(-1) min(-1)). RESULTS: VO2 at thetaL and at peak were
      significantly lower after NAC compared to pre-NAC values: VO2 at thetaL 14.5 +/-
      3.8 (baseline) vs. 12.3 +/- 3.0 (post-NAC) ml kg(-1) min(-1); p <= 0.001; VO2
      peak 20.8 +/- 6.0 vs. 18.3 +/- 5.1 ml kg(-1) min(-1); p <= 0.001; absolute VO2
      (ml min(-1)) at thetaL and peak were also lower post-NAC; p <= 0.001. Decreased
      baseline VO2 at thetaL and peak were associated with increased one year mortality
      in patients who completed a full course of NAC and had surgery; p = 0.014.
      CONCLUSION: NAC before cancer surgery significantly reduced physical fitness in
      the overall cohort. Lower baseline fitness was associated with reduced one-year
      survival in patients completing NAC and surgery, but not in patients who did not
      complete NAC. It is possible that in some patients the harms of NAC may outweigh
      the benefits. Trials Registry Number: NCT01335555.

PMID- 24731269
TI  - The delayed massive hemorrhage after gastrectomy in patients with gastric cancer:
      characteristics, management opinions and risk factors.
AB  - AIMS: This study was designed to investigate the clinical features of delayed
      massive hemorrhage (DMH) after gastrectomy in patients with gastric cancer (GC).
      METHODS: This study retrospectively reviewed 1536 GC patients with major
      gastrectomy between 1998 and 2011. Based on the time onset of postoperative
      bleeding, patients were divided into early postoperative hemorrhage (EPH),
      delayed massive hemorrhage (DMH), and no-bleeding groups. Postoperative
      mortality, bleeding treatment, and risk factors of hemorrhage were explored.
      RESULTS: In sum, 15 (0.9%) patients suffered from DMH, with three (20%) dead
      cases. None of 18 (1.2%) patients with EPH died, but there were three dead cases
      in no-bleeding group. DMH had more extra-intestinal bleeding (P = 0.037) than
      EPH. Angiographic embolization was performed in 12 (80%) of DMH patients and
      successful in ten cases. Surgical procedures were applied in only two
      embolization-failed cases. Extended lymphadenectomy (P = 0.038), vascular
      skeletonization (P = 0.012) and advanced TNM stage (P < 0.001) were correlated
      with DMH. CONCLUSIONS: DMH can be successfully managed with angiographic
      embolization, followed by alternative surgery. Extensive lymphadenectomy and
      vascular skeletonization should be discreetly performed during gastrectomy.

PMID- 24731270
TI  - Perceived problems with computer gaming and internet use among adolescents:
      measurement tool for non-clinical survey studies.
AB  - BACKGROUND: Existing instruments for measuring problematic computer and console
      gaming and internet use are often lengthy and often based on a pathological
      perspective. The objective was to develop and present a new and short non
      clinical measurement tool for perceived problems related to computer use and
      gaming among adolescents and to study the association between screen time and
      perceived problems. METHODS: Cross-sectional school-survey of 11-, 13-, and 15
      year old students in thirteen schools in the City of Aarhus, Denmark,
      participation rate 89%, n=2100. The main exposure was time spend on weekdays on
      computer- and console-gaming and internet use for communication and surfing. The
      outcome measures were three indexes on perceived problems related to computer and
      console gaming and internet use. RESULTS: The three new indexes showed high face
      validity and acceptable internal consistency. Most schoolchildren with high
      screen time did not experience problems related to computer use. Still, there was
      a strong and graded association between time use and perceived problems related
      to computer gaming, console gaming (only boys) and internet use, odds ratios
      ranging from 6.90 to 10.23. CONCLUSION: The three new measures of perceived
      problems related to computer and console gaming and internet use among
      adolescents are appropriate, reliable and valid for use in non-clinical surveys
      about young people's everyday life and behaviour. These new measures do not
      assess Internet Gaming Disorder as it is listed in the DSM and therefore has no
      parity with DSM criteria. We found an increasing risk of perceived problems with
      increasing time spent with gaming and internet use. Nevertheless, most
      schoolchildren who spent much time with gaming and internet use did not
      experience problems.

PMID- 24731271
TI  - Transmission of Escherichia coli O157:H7 in cattle is influenced by the level of
      environmental contamination.
AB  - A pen infection-transmission experiment was conducted to elucidate the role of
      pathogen strain and environmental contamination in transmission of Escherichia
      coli O157:H7 (ECO157) in cattle. Five steers were inoculated with a three-strain
      mixture of ECO157 and joined with five susceptible steers in each of two
      experimental replicates. Faecal and environmental samples were monitored for
      ECO157 presence over 30 days. One ECO157 strain did not spread. Transmission
      rates for the other two strains were estimated using a generalized linear model
      developed based on a modified 'Susceptible-Infectious-Susceptible' mathematical
      model. Transmission rates estimated for the two strains (0.11 and 0.14) were
      similar. However, the rates significantly (P = 0.0006) increased 1.5 times for
      every 1-unit increase in the level of environmental contamination measured as
      log10 c.f.u. Depending on the level of environmental contamination, the estimated
      basic reproduction numbers varied from <1 to 8. The findings indicate the
      importance of on-farm measures to reduce environmental contamination for ECO157
      control in cattle that should be validated under field conditions.

PMID- 24731272
TI  - Comparison of pH-sensitive degradability of maleic acid amide derivatives.
AB  - We synthesized five maleic acid amide derivatives (maleic, citraconic, cis
      aconitic, 2-(2'-carboxyethyl) maleic, 1-methyl-2-(2'-carboxyethyl) maleic acid
      amide), and compared their degradability for the future development of pH
      sensitive biomaterials with tailored kinetics of the release of drugs, the change
      of charge density, and the degradation of scaffolds. The degradation kinetics was
      highly dependent upon the substituents on the cis-double bond. Among the maleic
      acid amide derivatives, 2-(2'-carboxyethyl) maleic acid amide with one
      carboxyethyl and one hydrogen substituent showed appropriate degradability at
      weakly acidic pH, and the additional carboxyl group can be used as a pH-sensitive
      linker. 

PMID- 24731273
TI  - Design and synthesis of spirocyclic compounds as HCV replication inhibitors by
      targeting viral NS4B protein.
AB  - Two novel series of spirocyclic piperidine analogs appended to a pyrazolo[1,5
      a]pyridine core were designed, synthesized and evaluated for their anti-HCV
      activity. A series of piperidine ketals afforded dispiro 6p which showed
      excellent in vitro anti-HCV activities (EC50 of 1.5nM and 1.2nM against genotype
      1a and 1b replicons, respectively). A series of piperidine oxazolidinones
      afforded 27c which showed EC50's of 10.9nM and 6.1nM against 1a and 1b replicons,
      respectively. Both compounds 6p and 27c bound directly to non-structural NS4B
      protein in vitro (IC50's=10.2 and 30.4nM, respectively) and exhibited reduced
      potency in replicons containing resistance mutations encoding changes in the NS4B
      protein. 

PMID- 24731274
TI  - Synthesis, structure-activity relationships and biological evaluation of
      dehydroandrographolide and andrographolide derivatives as novel anti-hepatitis B
      virus agents.
AB  - Dehydroandrographolide and andrographolide, two natural diterpenoids isolated
      from Andrographis paniculata possessed activity against HBV DNA replication with
      IC50 values of 22.58 and 54.07MUM and low SI values of 8.7 and 3.7 in our random
      assay. Consequently, 48 derivatives of dehydroandrographolide and andrographolide
      were synthesized and evaluated for their anti-HBV properties to yield a series of
      active derivatives with lower cytotoxicity, including 14 derivatives against
      HBsAg secretion, 19 derivatives against HBeAg secretion and 38 derivatives
      against HBV DNA replication. Interestingly, compound 4e could inhibit not only
      HBsAg and HBeAg secretions but also HBV DNA replication with SI values of 20.3,
      125.0 and 104.9. Furthermore, the most active compound 2c with SI value higher
      than 165.1 inhibiting HBV DNA replication was revealed with the optimal logP
      value of 1.78 and logD values. Structure-activity relationships (SARs) of the
      derivatives were disclosed for guiding the future research toward the discovery
      of new anti-HBV drugs. 

PMID- 24731275
TI  - Design, syntheses, and characterization of piperazine based chemokine receptor
      CCR5 antagonists as anti prostate cancer agents.
AB  - Chemokine receptor CCR5 plays an important role in the pro-inflammatory
      environment that aids in the proliferation of prostate cancer cells. Previously,
      a series of CCR5 antagonists containing a piperidine ring core skeleton were
      designed based upon the proposed CCR5 antagonist pharmacophore from molecular
      modeling studies. The developed CCR5 antagonists were able to antagonize CCR5 at
      a micromolar level and inhibit the proliferation of metastatic prostate cancer
      cell lines. In order to further explore the structure-activity-relationship of
      the pharmacophore identified, the molecular scaffold was expanded to contain a
      piperazine ring as the core. A number of compounds that were synthesized showed
      promising anti prostate cancer activity and reasonable cytotoxicity profiles
      based on the biological characterization. 

PMID- 24731276
TI  - Design, synthesis, and SAR of embelin analogues as the inhibitors of PAI-1
      (plasminogen activator inhibitor-1).
AB  - The natural product embelin was found to have PAI-1 inhibitory activity with the
      IC50 value of 4.94MUM. Based on the structure of embelin, a series of analogues
      were designed, synthesized, and evaluated for their ability to inhibit PAI-1. The
      SAR study on these compounds disclosed that the inhibitory potency largely
      depended on the hydroxyl groups at C2 and C5, and the length of the alkyl chains
      at C3 and C6. Compound 11 displayed the best PAI-1 inhibitory potency with the
      IC50 value of 0.18MUM. 

PMID- 24731277
TI  - Small chemicals with inhibitory effects on PtdIns(3,4,5)P3 binding of Btk PH
      domain.
AB  - Phosphatidylinositol-3,4-5-triphosphates (PtdIns(3,4,5)P3) formed by
      phosphoinositide-3-kinase (PI3K) had been known as a signaling molecule that
      plays important roles in diverse cellular processes such as cell signaling,
      metabolism, cell differentiation, and apoptosis. PtdIns(3,4,5)P3 regulates
      diverse cellular processes by recruiting effector proteins to the specific
      cellular locations for correct functions. In this study, we reported the
      inhibitory effect of small chemicals on the interaction between PtdIns(3,4,5)P3
      Btk PH domain. Small chemicals were synthesized based on structural similarity of
      PtdInsP head-groups, and tested the inhibitory effects in vitro via surface
      plasmon resonance (SPR). As a result, the chemical 8 showed highest inhibitory
      effect with 17MUM of IC50 value. To elucidate diverse inhibitory effects of
      different small chemicals we employed in silico docking experiment using
      molecular modeling and simulation. The result of docking experiments showed
      chemical 8 has more hydrogen bonding with the residues in PtdIns(3,4,5)P3 binding
      site of Btk PH domain than others. Overall, our studies demonstrate the efficient
      approach to develop lipid binding inhibitors, and further we can use these
      chemicals to regulate effector proteins. In addition, our study would provide new
      insight that lipid binding domain may be the attractive therapeutic targets to
      treat severe human diseases. 

PMID- 24731278
TI  - Synthesis and in vitro evaluation of anti-inflammatory activity of ester and
      amine derivatives of indoline in RAW 264.7 and peritoneal macrophages.
AB  - A prolonged increase in pro-inflammatory cytokines, TNF-alpha and IL-6 occurs in
      inflammatory diseases. Although existing therapies like steroids and TNF-alpha
      antagonists are effective they may cause serious adverse effects. We describe the
      preparation and evaluation for anti-inflammatory activity of 11 novel derivatives
      of indoline carbamates with a propionic ester, 2-aminoethyl, 3-aminopropyl 2
      (dimethylamino)ethyl or 3-(dimethylamino)propyl group in positions 3 or 1.
      Compounds 25, 26 and 29 were previously shown to inhibit acetylcholinesterase
      with IC50s ranging from 0.4 to 55MUM and to prevent cytotoxicity induced by
      reactive oxygen species in a concentration range of 100pM-1MUM. Compounds 25, 26,
      29, 9, 10, 17 and 18, reduced NO, TNF-alpha and IL-6 at concentrations of 1-10pM
      in LPS-activated RAW-264.7 and mouse peritoneal macrophages. The reduction in
      cytokines by compound 25 was associated with an increase in IkappaBalpha
      degradation and a decrease in the phosphorylation of p38 but not that of ERK.
      CONCLUSION: Indoline derivatives substituted at position 3 with chains carrying
      ester or amino groups may have potential for the treatment of chronic
      inflammatory and neurodegenerative diseases.

PMID- 24731279
TI  - Differential DNA and RNA sequence discrimination by PNA having charged side
      chains.
AB  - PNA sequences modified with charged side chains were evaluated for base-pairing
      sequence selectivity under physiological conditions. PNA having negatively
      charged aspartic acid side chains shows higher selectivity with RNA, while PNA
      having positively charged lysine side chains shows higher selectivity with DNA.
      These observations provide insight into the binding selectivity of modified PNA
      in antisense and antigene applications. 

PMID- 24731280
TI  - Structural characterization of P1'-diversified urea-based inhibitors of glutamate
      carboxypeptidase II.
AB  - Urea-based inhibitors of human glutamate carboxypeptidase II (GCPII) have
      advanced into clinical trials for imaging metastatic prostate cancer. In parallel
      efforts, agents with increased lipophilicity have been designed and evaluated for
      targeting GCPII residing within the neuraxis. Here we report the structural and
      computational characterization of six complexes between GCPII and P1'-diversified
      urea-based inhibitors that have the C-terminal glutamate replaced by more
      hydrophobic moieties. The X-ray structures are complemented by quantum mechanics
      calculations that provide a quantitative insight into the GCPII/inhibitor
      interactions. These data can be used for the rational design of novel glutamate
      free GCPII inhibitors with tailored physicochemical properties. 

PMID- 24731281
TI  - Synthesis and biological evaluation of compounds which contain pyrazole, thiazole
      and naphthalene ring as antitumor agents.
AB  - A series of compounds which contain pyrazole, thiazole and naphthalene ring (1a
      7a, 1b-7b, 1c-7c, 1d-7d) were firstly synthesized and their anti-proliferative
      activity, EGFR inhibitory activity, cytotoxicity and inhibition to Hela cell
      migration were evaluated. Compound 2-(3-(3,4-dimethylphenyl)-5-(naphthalen-2-yl)
      4,5-dihydro-1H-pyrazol-1-yl)thiazol-4(5H)-one (7d) displayed the most potent
      inhibitory activity (IC50=0.86MUM for Hela and IC50=0.12MUM for EGFR). Structure
      activity relationship (SAR) analysis showed that the anti-proliferative activity
      was affected by A-ring-substituent (-OCH3>-CH3>-H>-Br>-Cl>-F). Docking simulation
      of compound 7d into EGFR active site showed that naphthalene ring of 7d with
      LYS721 formed two p-pi bonds, which enhanced antitumor activity. Therefore,
      compound 7d may be developed as a potential antitumor agent. 

PMID- 24731282
TI  - A marriage of convenience; a simple food chain comprised of Lemna minor (L.) and
      Gammarus pulex (L.) to study the dietary transfer of zinc.
AB  - Macrophytes contribute significantly to the cycling of metals in aquatic systems,
      through accumulation during growth and release during herbivory or decomposition.
      Accumulation of high levels of metals has been extensively documented in
      Lemnaceae (duckweeds). However, the degree of trophic transfer of metals from
      Lemnaceae to secondary consumers remains poorly understood. This study
      demonstrates that zinc accumulated in Lemna minor is bioavailable to the
      herbivore consumer Gammarus pulex. Overall, the higher the zinc content of L.
      minor, the more zinc accumulated in G. pulex. Accumulation in G. pulex was such
      that mortality occurred when they were fed high zinc-containing L. minor. Yet,
      the percentage of consumed zinc retained by G. pulex actually decreased with
      higher zinc concentrations in L. minor. We hypothesise that this decrease
      reflects internal zinc metabolism, including a shift from soluble to covalently
      bound zinc in high zinc-containing L. minor. Consistently, relatively more zinc
      is lost through depuration when G. pulex is fed L. minor with high zinc content.
      The developed Lemna-Gammarus system is simple, easily manipulated, and sensitive
      enough for changes in plant zinc metabolism to be reflected in metal accumulation
      by the herbivore, and therefore suitable to study ecologically relevant metal
      cycling in aquatic ecosystems.

PMID- 24731283
TI  - Use of a standardized diagnostic approach improves the prognostic information of
      histopathologic factors in pancreatic and periampullary adenocarcinoma.
AB  - BACKGROUND: Variability in reported histopathology parameters in operated
      periampullary adenocarcinomas may affect the prognostic weight of the parameters.
      Standardized axial sectioning produces a higher incidence of involved margins and
      also seems to produce a lower relative incidence of pancreatic compared with
      distal bile duct origin and a higher incidence of involved lymph nodes, compared
      with non-standardized procedure. The aims of this study were to 1) assess how a
      previously not described standardized pathology procedure, with longitudinal
      sectioning along the distal bile duct, affects reported tumour origin, margin
      status and involved lymph nodes, compared with non-standardized procedure, 2)
      assess if re-evaluation of microscopic slides affects the prognostic value of
      margin status and 3) compare the results of this standardized procedure with
      reported results of other standardized and non-standardized procedures. METHODS:
      One hundred seventy-five consecutive pancreaticoduodenectomy specimens with
      primary adenocarcinomas, operated during 2001 - 2011 at the University hospitals
      of Lund and Malmo, Sweden, were re-evaluated histologically, and parameters
      relevant for classification and prognosis were assessed, with 1 mm as a threshold
      for involved or uninvolved margins. Follow-up lasted until 31 December 2013. Five
      year overall survival (OS) and hazard ratios (HR) were calculated for the margin
      status stated in the original reports and margin status after re-evaluation.
      RESULTS: Compared with non-standardized cases (n = 129), standardized cases (n =
      46) had more involved lymph nodes in the specimens (median 3 vs 1), a higher
      fraction of distal bile duct origin (39% vs 21%) and a higher fraction of
      involved margins (74% vs 47%). The prognostic value of uninvolved margins
      increased by re-evaluation of slides (p < 0.001) and the adjusted HR for involved
      margins increased from 1.6 (95% CI 1.1 - 2.4) to 3.3 (95% CI 1.5 - 7.0).
      Uninvolved margins remained a significant predictor of OS in adjusted analysis.
      CONCLUSIONS: Both the method of sectioning the specimen and the microscopic
      assessment affect prognostic pathology parameters significantly. The results of
      the herein described standardized method are similar to the results of other
      standardized procedures. The 1-mm threshold for involved margins in
      pancreaticoduodenectomies is relevant for OS, and margin status is an independent
      prognostic parameter. VIRTUAL SLIDES: The virtual slides for this article can be
      found here: http://www.diagnosticpathology.diagnomx.eu/vs/1056639379120615.

PMID- 24731284
TI  - Cetuximab induces eme1-mediated DNA repair: a novel mechanism for cetuximab
      resistance.
AB  - Overexpression of the epidermal growth factor receptor (EGFR) is observed in a
      large number of neoplasms. The monoclonal antibody cetuximab/Erbitux is
      frequently applied to treat EGFR-expressing tumors. However, the application of
      cetuximab alone or in combination with radio- and/or chemotherapy often yields
      only little benefit for patients. In the present study, we describe a mechanism
      that explains resistance of both tumor cell lines and cultured primary human
      glioma cells to cetuximab. Treatment of these cells with cetuximab promoted DNA
      synthesis in the absence of increased proliferation, suggesting that DNA repair
      pathways were activated. Indeed, we observed that cetuximab promoted the
      activation of the DNA damage response pathway and prevented the degradation of
      essential meiotic endonuclease 1 homolog 1 (Eme1), a heterodimeric endonuclease
      involved in DNA repair. The increased levels of Eme1 were necessary for enhanced
      DNA repair, and the knockdown of Eme1 was sufficient to prevent efficient DNA
      repair in response to ultraviolet-C light or megavoltage irradiation. These
      treatments reduced the survival of tumor cells, an effect that was reversed by
      cetuximab application. Again, this protection was dependent on Eme1. Taken
      together, these results suggest that cetuximab initiates pathways that result in
      the stabilization of Eme1, thereby resulting in enhanced DNA repair. Accordingly,
      cetuximab enhances DNA repair, reducing the effectiveness of DNA-damaging
      therapies. This aspect should be considered when using cetuximab as an antitumor
      agent and suggests that Eme1 is a negative predictive marker. 

PMID- 24731285
TI  - Factors influencing adherence in Hepatitis-C infected patients: a systematic
      review.
AB  - BACKGROUND: Adherence is a crucial point for the successful treatment of a
      hepatitis-C virus infection. Studies have shown that especially adherence to
      ribavirin is important.The objective of this systematic review was to identify
      factors that influence adherence in hepatitis-C infected patients taking regimes
      that containing ribavirin. METHODS: A systematic literature search was performed
      in Medline and Embase in March 2014 without limits for publication date. Titles
      and abstracts and in case of relevance, full-texts were screened according to
      predefined inclusion criteria. The risk of bias was assessed. Both process steps
      were carried out independently by two reviewers. Relevant data on study
      characteristics and results were extracted in standardized tables by one reviewer
      and checked by a second. Data were synthesized in a narrative way using a
      standardized procedure. RESULTS: Nine relevant studies were identified. The
      number of analyzed patients ranged between 12 and 5706 patients. The study
      quality was moderate. Especially the risk of bias regarding the measurement of
      influencing factors was mostly unclear."Psychiatric disorders" (N = 5) and having
      to take "higher doses of ribavirin" (N = 3) showed a negative influence on
      adherence. In contrast, a "HIV co-infection" (N = 2) and the "hemoglobin level"
      (N = 2) were associated with a positive influence on adherence. Furthermore,
      there is the tendency that male patients are more adherent than female patients
      (N = 6). "Alcohol consumption" (N = 2), "education", "employment status", "ethnic
      group","hepatitis-C virus RNA" (N = 4), "genotype" (N = 5), "metavir activity" (N
      = 1) and "weight" (N = 3) showed mostly no effect on adherence. Although, some
      studies showed statistically significant results for "age", "drug use" ,
      "genotype", "medication dose interferon", and "treatment experience" the effect
      is unclear because effect directions were partly conflicting.The other factors
      were heterogeneous regarding the effect direction and/or statistical
      significance. CONCLUSION: There are some factors that seem to show an influence
      on adherence. However, due to the heterogeneity (e.g. patient characteristics,
      regimes, settings, countries) no general conclusions can be made. The results
      should rather be considered as indications for factors that can have an influence
      on adherence in hepatitis-C infected patients taking regimes that containing
      ribavirin.

PMID- 24731286
TI  - Transcription of the three HMG-CoA reductase genes of Mucor circinelloides.
AB  - BACKGROUND: Precursors of sterols, carotenoids, the prenyl groups of several
      proteins and other terpenoid compounds are synthesised via the acetate-mevalonate
      pathway. One of the key enzyme of this pathway is the 3-hydroxy-3-methylglutaryl
      CoA (HMG-CoA) reductase, which catalyses the conversion of HMG-CoA to mevalonate.
      HMG-CoA reductase therefore affects many biological processes, such as
      morphogenesis, synthesis of different metabolites or adaptation to environmental
      changes. In this study, transcription of the three HMG-CoA reductase genes
      (designated as hmgR1, hmgR2 and hmgR3) of the beta-carotene producing Mucor
      circinelloides has been analysed under various culturing conditions; effect of
      the elevation of their copy number on the carotenoid and ergosterol content as
      well as on the sensitivity to statins has also been examined. RESULTS:
      Transcripts of each gene were detected and their relative levels varied under the
      tested conditions. Transcripts of hmgR1 were detected only in the mycelium and
      its relative transcript level seems to be strongly controlled by the temperature
      and the oxygen level of the environment. Transcripts of hmgR2 and hmgR3 are
      already present in the germinating spores and the latter is also strongly
      regulated by oxygen. Overexpression of hmgR2 and hmgR3 by elevating their copy
      numbers increased the carotenoid content of the fungus and decreased their
      sensitivity to statins. CONCLUSIONS: The three HMG-CoA reductase genes of M.
      circinelloides displayed different relative transcript levels under the tested
      conditions suggesting differences in their regulation. They seem to be especially
      involved in the adaptation to the changing oxygen tension and osmotic conditions
      of the environment as well as to statin treatment. Overexpression of hmgR2 and
      hmgR3 may be used to improve the carotenoid content.

PMID- 24731287
TI  - The prevalence of Borrelia miyamotoi infection, and co-infections with other
      Borrelia spp. in Ixodes scapularis ticks collected in Canada.
AB  - BACKGROUND: Blacklegged ticks, Ixodes scapularis are vectors of the tick-borne
      pathogens Borrelia burgdorferi, Anaplasma phagocytophilum and Babesia microti.
      Recently, the I. scapularis-borne bacterium Borrelia miyamotoi has been linked to
      human illness in North America. The range of this tick is expanding in Canada
      which may increase the potential for human exposure to these agents. METHODS: In
      this study, 4938 I. scapularis ticks collected in 2012 were tested following a
      newly developed PCR-based testing protocol to determine the prevalence of
      infection with B. miyamotoi and other pathogens in I. scapularis in Canada.
      RESULTS: Borrelia miyamotoi was detected in blacklegged ticks from all provinces
      except Newfoundland, although the infection prevalence was low (<1%). There was
      significant variation among provinces in the prevalence of infection of ticks
      with B. burgdorferi and A. phagocytophilum, but not with B. miyamotoi.
      CONCLUSIONS: Given the widespread distribution of B. miyamotoi, infection due to
      this agent should be considered in patients who have been exposed to blacklegged
      ticks in Canada.

PMID- 24731289
TI  - Synthesis of cytocompatible luminescent titania/fluorescein hybrid nanoparticles.
AB  - Luminescent titania-fluorescein (FS) hybrid nanoparticles (NPs) were successfully
      synthesized by a sol-gel reaction of titanium alkoxide in the presence of
      octadecylamine using a fluidic reactor with a Y-type channel. The molar ratio of
      FS/Ti ratio was varied in the range from 1/1000 to 1/100 in order to obtain the
      hybrid NPs with the different luminescent behavior. The shape of the NPs is
      spherical and their sizes are 400 nm which is almost the same irrespective of the
      FS content, suggesting the different FS molecular states in one NP. We also
      demonstrated that the hybrid NPs exhibited a characteristic luminescence; the NPs
      with the higher and lower FS contents exhibited an enhanced luminescence in PBS
      and air, respectively, indicating that the FS states responded to the molecular
      environment. Through cytocompatible experiments using the NPs, it turned out that
      they had a high compatibility for fibroblasts. Therefore, the preparation of a
      series of the luminescent NPs with a tunable luminescence property was achieved.
      The results will lead to a guideline to determine a proper combination between
      material composition and an environment where they are used, being useful for
      biomedical applications. 

PMID- 24731288
TI  - Repositioning: the fast track to new anti-malarial medicines?
AB  - BACKGROUND: Repositioning of existing drugs has been suggested as a fast track
      for developing new anti-malarial agents. The compound libraries of
      GlaxoSmithKline (GSK), Pfizer and AstraZeneca (AZ) comprising drugs that have
      undergone clinical studies in other therapeutic areas, but not achieved approval,
      and a set of US Food and Drug Administration (FDA)-approved drugs and other bio
      actives were tested against Plasmodium falciparum blood stages. METHODS:
      Molecules were tested initially against erythrocytic co-cultures of P. falciparum
      to measure proliferation inhibition using one of the following methods: SYBR(r)I
      dye DNA staining assay (3D7, K1 or NF54 strains); [(3)H] hypoxanthine
      radioisotope incorporation assay (3D7 and 3D7A strain); or 4',6-diamidino-2
      phenylindole (DAPI) DNA imaging assay (3D7 and Dd2 strains). After review of the
      available clinical pharmacokinetic and safety data, selected compounds with low
      MUM activity and a suitable clinical profile were tested in vivo either in a
      Plasmodium berghei four-day test or in the P. falciparum Pf3D7(0087/N9) huSCID
      'humanized' mouse model. RESULTS: Of the compounds included in the GSK and Pfizer
      sets, 3.8% (9/238) had relevant in vitro anti-malarial activity while 6/100
      compounds from the AZ candidate drug library were active. In comparison, around
      0.6% (24/3,800) of the FDA-approved drugs and other bio-actives were active.
      After evaluation of available clinical data, four investigational drugs, active
      in vitro were tested in the P. falciparum humanized mouse model: UK-112,214 (PAF
      H1 inhibitor), CEP-701 (protein kinase inhibitor), CEP-1347 (protein kinase
      inhibitor), and PSC-833 (p-glycoprotein inhibitor). Only UK-112,214 showed
      significant efficacy against P. falciparum in vivo, although at high doses (ED90
      131.3 mg/kg [95% CI 112.3, 156.7]), and parasitaemia was still present 96 hours
      after treatment commencement. Of the six actives from the AZ library, two
      compounds (AZ-1 and AZ-3) were marginally efficacious in vivo in a P. berghei
      model. CONCLUSIONS: Repositioning of existing therapeutics in malaria is an
      attractive proposal. Compounds active in vitro at MUM concentrations were
      identified. However, therapeutic concentrations may not be effectively achieved
      in mice or humans because of poor bio-availability and/or safety concerns.
      Stringent safety requirements for anti-malarial drugs, given their widespread use
      in children, make this a challenging area in which to reposition therapy.

PMID- 24731290
TI  - Can cholesterol be used to distinguish pleural exudates from transudates?
      evidence from a bivariate meta-analysis.
AB  - BACKGROUND: Many studies have investigated whether pleural cholesterol levels can
      aid in diagnosis of pleural exudates, and the results have varied considerably.
      To gain a more reliable answer to this question, we meta-analyzed the literature
      on using pleural cholesterol or the ratio of cholesterol in pleural fluid to
      cholesterol in serum (P/S cholesterol ratio) as diagnostic tests to help identify
      pleural exudates. METHODS: Literature databases were systematically searched for
      studies examining accuracy of pleural cholesterol or P/S cholesterol ratios for
      diagnosing pleural exudates. Data on sensitivity, specificity, positive/negative
      likelihood ratio (PLR/NLR), and diagnostic odds ratio (DOR) were pooled using
      bivariate-effects models. Summary receiver operating characteristic (SROC) curves
      and area under the curve (AUC) were used to summarize overall test performance.
      RESULTS: Our meta-analysis included up to 20 studies involving 3,496 subjects.
      Summary estimates for pleural cholesterol in the diagnosis of pleural exudates
      were as follows: sensitivity, 0.88 (95%CI 0.84 to 0.92); specificity, 0.96 (95%
      CI 0.92 to 0.98); PLR, 20.31 (95% CI 11.21 to 36.78); NLR, 0.12 (95% CI 0.09 to
      0.17); DOR, 167.06 (95% CI 76.79 to 363.95); and AUC 0.97 (95% CI 0.95 to 0.98).
      The corresponding summary performance estimates for using the P/S cholesterol
      ratio were as follows: sensitivity, 0.94 (95% CI 0.92 to 0.96); specificity, 0.87
      (95% CI 0.83 to 0.91); PLR 7.46 (95% CI, 5.47 to 10.19); NLR, 0.07 (95% CI 0.05
      to 0.10); DOR, 107.74 (95% CI 60.91 to 190.60); and AUC 0.97 (95% CI 0.95 to
      0.98). CONCLUSIONS: Both pleural cholesterol level and the P/S cholesterol ratio
      are helpful for the diagnosis of pleural exudates. Nevertheless, the results of
      pleural cholesterol assays should be interpreted in parallel with the results of
      traditional tests and clinical information.

PMID- 24731291
TI  - Interacting effects of pollination, water and nutrients on fruit tree
      performance.
AB  - Pollination is critical to fruit production, but the interactions of pollination
      with plant resources on a plant's reproductive and vegetative features are
      largely overlooked. We examined the influences of pollination, irrigation and
      fertilisation on the performance of almond, Prunus dulcis, in northern
      California. We used a full-factorial design to test for the effects of
      pollination limitation on fruit production and foliage variables of whole trees
      experiencing four resource treatments: (i) normal water and nutrients, (ii)
      reduced water, (iii) no nutrients, and (iv) reduced water and no nutrients. In
      each of these combinations, we applied three pollination treatments: hand-cross
      pollination, open-pollination and pollinator exclusion. Pollination strongly
      affected yield even under reduced water and no nutrient applications. Hand-cross
      pollination resulted in over 50% fruit set with small kernels, while open
      pollinated flowers showed over 30% fruit set with moderate-sized kernels.
      Pollinator-excluded flowers had a maximum fruit set of 5%, with big and heavy
      kernels. Reduced water interacted with the open- and hand-cross pollination
      treatments, reducing yield more than in the pollinator exclusion treatment. The
      number of kernels negatively influenced the number of leaves, and reduced water
      and no nutrient applications interacted with the pollination treatments. Overall,
      our results indicate that the influences of pollination on fruit tree yield
      interact with the plant availability of nutrients and water and that excess
      pollination can reduce fruit quality and the production of leaves for
      photosynthesis. Such information is critical to understand how pollination
      influences fruit tree performance. 

PMID- 24731293
TI  - Human neutrophil alpha-defensins are associated with adenosine diphosphate
      inducible neutrophil-platelet aggregate formation and response to clopidogrel in
      patients with atherosclerosis.
AB  - Human neutrophil alpha-defensins (HNPs) are antimicrobial peptides stored
      primarily in the azurophilic granules of polymorphonuclear leukocytes. Recently,
      it was shown that HNPs act as platelet agonists. We hypothesized that HNP levels
      are associated with the formation of neutrophil-platelet aggregates, and that
      they influence the response to clopidogrel therapy. HNP levels were determined by
      a commercially available enzyme-linked immunosorbent assay in 305 patients
      undergoing angioplasty and stenting for atherosclerotic cardiovascular disease.
      Neutrophil-platelet aggregates were measured by flow cytometry, and on-treatment
      platelet reactivity was determined using the VerifyNow P2Y12 and aspirin assays.
      HNP levels did not correlate with the formation of neutrophil-platelet aggregates
      in vivo (r = 0.05, P = 0.4). In contrast, HNP levels correlated significantly
      with adenosine diphosphate (ADP)-inducible neutrophil-platelet aggregate
      formation (r = 0.13, P = 0.04). On-treatment platelet reactivity by the VerifyNow
      P2Y12 assay was significantly more pronounced in patients with high HNP levels
      compared with patients with low HNP levels (211 P2Y12 reaction units [PRU; range,
      143-293 PRU] vs 181 PRU [range, 129-237 PRU], P = 0.009). This association
      remained significant after adjusting for high-sensitivity C-reactive protein and
      interleukin 6 by multivariate regression analysis (P = 0.007). Moreover, high on
      treatment residual platelet reactivity by the VerifyNow P2Y12 assay was more
      frequent in patients with high HNP levels than in patients with low HNP levels
      (40% vs 26.6%, P = 0.01). In conclusion, HNP levels are associated with ADP
      inducible neutrophil-platelet aggregate formation and clopidogrel-mediated
      platelet inhibition. High levels of HNPs may, in part, be responsible for the
      observed response variability to clopidogrel. 

PMID- 24731292
TI  - Epimorphin(-/-) mice are protected, in part, from acute colitis via decreased
      interleukin 6 signaling.
AB  - Epimorphin (Epim), a member of the syntaxin family of membrane-bound,
      intracellular vesicle-docking proteins, is expressed in intestinal myofibroblasts
      and macrophages. We demonstrated previously that Epimorphin(-/-)(Epim(-/-)) mice
      are protected, in part, from dextran sodium sulfate (DSS)-induced colitis.
      Although interleukin (IL)-6/p-Stat3 signaling has been implicated in the
      pathogenesis of colitis, the myofibroblast contribution to IL-6 signaling in
      colitis remains unexplored. Our aim was to investigate the IL-6 pathway in Epim(
      /-) mice in the DSS colitis model. Whole colonic tissue, epithelium, and stroma
      of WT and congenic Epim(-/-) mice treated with 5% DSS for 7 days were analyzed
      for IL-6 and a downstream effector, p-Stat3, by immunostaining and immunoblot.
      Colonic myofibroblast and peritoneal macrophage IL-6 secretion were evaluated by
      enzyme-linked immunosorbent assay. IL-6 and p-Stat3 expression were decreased in
      Epim(-/-) vs WT colon. A relative increase in stromal vs epithelial p-Stat3
      expression was observed in WT mice but not in Epim(-/-) mice. Epim deletion
      abrogates IL-6 secretion from colonic myofibroblasts treated with IL-1beta and
      decreases IL-6 secretion from peritoneal macrophages in a subset of DSS-treated
      mice. Epim deletion inhibits IL-6 secretion most profoundly from colonic
      myofibroblasts. Distribution of Stat3 activation is altered in DSS-treated Epim(
      /-) mice. Our findings support the notion that myofibroblasts modulate IL-6/p
      Stat3 signaling in DSS-treated Epim(-/-) mice.

PMID- 24731294
TI  - National patterns of Escherichia coli O157 infections, USA, 1996-2011.
AB  - US public health laboratories began reporting Escherichia coli O157 isolates to
      CDC in 1996. We describe temporal and geographical patterns of isolates reported
      from 1996 to 2011 and demographics of persons whose specimens yielded isolates.
      We calculated annual E. coli O157 isolation rates/100 000 persons by patient's
      state of residence, county of residence, age, and sex using census data. The
      average annual isolation rate was 0.84. The average isolation rate in northern
      states (1.52) was higher than in southern states (0.43). Counties with ?76% rural
      population had a lower isolation rate (0.67) than counties with ?25%, 26-50%, and
      51-75% rural populations (0.81, 0.92, and 0.81, respectively). The highest
      isolation rate (3.19) was in children aged 1-4 years. Infections were seasonal
      with 49% of isolates collected during July to September. Research into reasons
      for higher incidence in northern states and for seasonality could guide
      strategies to prevent illnesses.

PMID- 24731295
TI  - The Implementation Leadership Scale (ILS): development of a brief measure of unit
      level implementation leadership.
AB  - BACKGROUND: In healthcare and allied healthcare settings, leadership that
      supports effective implementation of evidenced-based practices (EBPs) is a
      critical concern. However, there are no empirically validated measures to assess
      implementation leadership. This paper describes the development, factor
      structure, and initial reliability and convergent and discriminant validity of a
      very brief measure of implementation leadership: the Implementation Leadership
      Scale (ILS). METHODS: Participants were 459 mental health clinicians working in
      93 different outpatient mental health programs in Southern California, USA.
      Initial item development was supported as part of a two United States National
      Institutes of Health (NIH) studies focused on developing implementation
      leadership training and implementation measure development. Clinician work
      group/team-level data were randomly assigned to be utilized for an exploratory
      factor analysis (n = 229; k = 46 teams) or for a confirmatory factor analysis (n
      = 230; k = 47 teams). The confirmatory factor analysis controlled for the
      multilevel, nested data structure. Reliability and validity analyses were then
      conducted with the full sample. RESULTS: The exploratory factor analysis resulted
      in a 12-item scale with four subscales representing proactive leadership,
      knowledgeable leadership, supportive leadership, and perseverant leadership.
      Confirmatory factor analysis supported an a priori higher order factor structure
      with subscales contributing to a single higher order implementation leadership
      factor. The scale demonstrated excellent internal consistency reliability as well
      as convergent and discriminant validity. CONCLUSIONS: The ILS is a brief and
      efficient measure of unit level leadership for EBP implementation. The
      availability of the ILS will allow researchers to assess strategic leadership for
      implementation in order to advance understanding of leadership as a predictor of
      organizational context for implementation. The ILS also holds promise as a tool
      for leader and organizational development to improve EBP implementation.

PMID- 24731296
TI  - A prediction model for renal artery stenosis using carotid ultrasonography
      measurements in patients undergoing coronary angiography.
AB  - BACKGROUND: Carotid intima-media thickness (CIMT) and carotid atherosclerotic
      plaque (CAP) are well-known indicators of atherosclerosis. However, few studies
      have reported the value of CIMT and CAP for predicting renal artery stenosis
      (RAS). We investigated the predictive value of CIMT and CAP for RAS and propose a
      model for predicting significant RAS in patients undergoing coronary angiography
      (CAG). METHODS: Consecutive patients who underwent renal angiography at the time
      of CAG in a single center in 2011 were included. RAS >=50% was considered
      significant. Multiple logistic regression analysis with step-down variable
      selection method was used to select the best model for predicting significant RAS
      and bootstrap resampling was used to validate the best model. A scoring system
      for predicting significant RAS was developed by adding the closest integers
      proportional to the coefficients of the regression formula. RESULTS: Significant
      RAS was observed in 60 of 641 patients (9.6%) who underwent CAG. Hypertension,
      diabetes, significant coronary artery disease (CAD) and chronic kidney disease
      (CKD) stage >=3 were more prevalent in patients with significant RAS. Mean age,
      CIMT and number of anti-hypertensive medications (AHM) were higher and body mass
      index (BMI) and total cholesterol level were lower in patients with significant
      RAS. Multiple logistic regression analysis identified significant CAD (odds ratio
      (OR) 5.6), unilateral CAP (OR 2.6), bilateral CAP (OR 4.9), CKD stage >=3 (OR
      4.8), four or more AHM (OR 4.8), CIMT (OR 2.3), age >=67 years (OR 2.3) and BMI
      <22 kg/m2 (OR 2.4) as independent predictors of significant RAS. The scoring
      system for predicting significant RAS, which included these predictors, had a
      sensitivity of 83.3% and specificity of 81.6%. The predicted frequency of the
      scoring system agreed well with the observed frequency of significant RAS
      (coefficient of determination r2 = 0.957). CONCLUSIONS: CIMT and CAP are
      independent predictors of significant RAS. The proposed scoring system, which
      includes CIMT and CAP, may be useful for predicting significant RAS in patients
      undergoing CAG.

PMID- 24731297
TI  - Evaluation of larvicidal activity of the essential oil of Allium macrostemon
      Bunge and its selected major constituent compounds against Aedes albopictus
      (Diptera: Culicidae).
AB  - BACKGROUND: During the screening programme for new agrochemicals from Chinese
      medicinal herbs and local wild plants, the essential oil of dried bulbs of Allium
      macrostemon Bunge (Liliaceae) was found to possess larvicidal activity against
      mosquitoes. The aim of this research was to determine the larvicidal activity of
      the essential oil and its major constituent compounds against the larvae of the
      Culicidae mosquito, Aedes albopictus. METHODS: Essential oil of A. macrostemon
      was obtained by hydrodistillation and analyzed by gas chromatography (GC) and gas
      chromaotography-mass spectrometry (GC-MS). The activity of the essential oil and
      its two major constituents were evaluated, using World Health Organization (WHO)
      procedures, against the fourth instar larvae of Ae. albopictus for 24 h and
      larval mortalities were recorded at various essential oil/compound concentrations
      ranging from 9.0 - 150 MUg/ml. RESULTS: The essential oil of A. macrostemon
      exhibited larvicidal activity against the early fourth instar larvae of Ae.
      albopictus with an LC50 value of 72.86 MUg/ml. The two constituent compounds,
      dimethyl trisulfide and methyl propyl disulfide possessed strong larvicidal
      activity against the early fourth instar larvae of Ae. albopictus with LC50
      values of 36.36 MUg/ml and 86.16 MUg/ml, respectively. CONCLUSION: The results
      indicated that the essential oil of A. macrostemon and its major constituents
      have good potential as a source for natural larvicides.

PMID- 24731299
TI  - Nitrogen/carbon atomic ratio-dependent performances of nitrogen-doped carbon
      coated metal oxide nanocrystals for anodes in lithium-ion batteries.
AB  - We report the hydrothermal synthesis of the N-doped carbon-coated NiO
      nanocrystals (N-C-NiO NCs) with tunable N/C atomic ratios using the nitrogen
      containing ionic liquids (ILs) as new carbon precursor, and the N-doped carbon
      layer composition-dependent performances of N-C-NiO NCs anode for lithium-ion
      batteries (LIBs). The results indicate that the N-doped carbon coating can
      significantly enhance the electronic conductivity, effectively avoid the problems
      of cracking or pulverization of the NiO, and prevent the aggregation of the
      active materials upon cycling. These properties make the synthesized material a
      promising anode material for LIBs. The N-C-NiO NCs with the N/C atomic ratio of
      21.2% in the N-doped carbon layer show a high specific capacity of ~710 mAh g(-1)
      at a current rate of 0.3 C (very closed to the theoretical capacity of 718 mAh g(
      1) for NiO), a high rate capability (still able to deliver a discharge capacity
      of ~430 mAh g(-1) at a current density of 10 C), and good capacity retention upon
      cycling (maintains at 710 mAh g(-1) at least up to the 50th cycle) compared with
      those of pristine NiO nanoparticles. Moreover, the electrochemical performances
      of the N-C-NiO NCs depend on the composition (N/C atomic ratios) in the N-doped
      carbon layer and are enhanced with increasing of the N/C ratios. Our approach
      offers an effective and convenient technique to improve the specific capacities
      and rate capabilities of highly insulating electrode materials for batteries and
      may also provide general and effective approach toward the synthesis of other
      metal oxides coated with N-doped carbon layer. 

PMID- 24731298
TI  - Geographical variation in Plasmodium vivax relapse.
AB  - BACKGROUND: Plasmodium vivax has the widest geographic distribution of the human
      malaria parasites and nearly 2.5 billion people live at risk of infection. The
      control of P. vivax in individuals and populations is complicated by its ability
      to relapse weeks to months after initial infection. Strains of P. vivax from
      different geographical areas are thought to exhibit varied relapse timings. In
      tropical regions strains relapse quickly (three to six weeks), whereas those in
      temperate regions do so more slowly (six to twelve months), but no comprehensive
      assessment of evidence has been conducted. Here observed patterns of relapse
      periodicity are used to generate predictions of relapse incidence within
      geographic regions representative of varying parasite transmission. METHODS: A
      global review of reports of P. vivax relapse in patients not treated with a
      radical cure was conducted. Records of time to first P. vivax relapse were
      positioned by geographic origin relative to expert opinion regions of relapse
      behaviour and epidemiological zones. Mixed-effects meta-analysis was conducted to
      determine which geographic classification best described the data, such that a
      description of the pattern of relapse periodicity within each region could be
      described. Model outputs of incidence and mean time to relapse were mapped to
      illustrate the global variation in relapse. RESULTS: Differences in relapse
      periodicity were best described by a historical geographic classification system
      used to describe malaria transmission zones based on areas sharing zoological and
      ecological features. Maps of incidence and time to relapse showed high relapse
      frequency to be predominant in tropical regions and prolonged relapse in
      temperate areas. CONCLUSIONS: The results indicate that relapse periodicity
      varies systematically by geographic region and are categorized by nine global
      regions characterized by similar malaria transmission dynamics. This indicates
      that relapse may be an adaptation evolved to exploit seasonal changes in vector
      survival and therefore optimize transmission. Geographic patterns in P. vivax
      relapse are important to clinicians treating individual infections,
      epidemiologists trying to infer P. vivax burden, and public health officials
      trying to control and eliminate the disease in human populations.

PMID- 24731300
TI  - Characteristics of South African patients presenting with kidney disease in rural
      KwaZulu-Natal: a cross sectional study.
AB  - BACKGROUND: Diabetes mellitus is the leading cause of end-stage renal disease
      (ESRD) globally. Diabetes and human immunodeficiency virus (HIV), both prevalent
      in South Africa, have not been reported as significant causes of ESRD. METHODS:
      We evaluated chronic kidney disease (CKD) and cardiovascular disease risk factors
      in a cross-sectional study of 302 patients (165 females/ 137 males) at a CKD
      clinic in rural northern KwaZulu-Natal. We included all CKD outpatient clinic
      attendees and excluded acute renal failure patients. Demographic, clinical and
      laboratory data collected were analyzed with Stata11 software. Logistic
      regression analysis was used to determine factors associated with advanced CKD
      and results expressed as the odds ratio with the 95% confidence interval [OR (95%
      CI)]. RESULTS: Of 302 patients analyzed, 290 (96%) were black African. Mean age
      +/- SD was 47.1 +/- 17.0 years. Approximately 86.4% of females and 54.5% of males
      were overweight/ obese. Dyslipidaemia was observed in 47.9% females and 29.2%
      males (P < 0.001). Estimated glomerular filtration rate (eGFR) was <30
      ml/min/1.73 m2 in 50.6% patients. CKD risk factors observed were: hypertension
      (77.8%), diabetes (29.8%), HIV (28.5%), glomerulonephritis (7.0%) and
      tubulointerstitial diseases (5.6%). Independent factors associated with eGFR <30
      ml/min/1.73 m2 at presentation were: HIV [OR = 2.4 (1.3-4.2), P = 0.004] and
      hypertension [OR = 2.3 (1.3-4.2), P = 0.007]. CONCLUSION: Diabetes and HIV are
      prevalent in CKD patients at primary/regional level healthcare in South Africa.
      With registry data lacking, dedicated CKD clinics at lower healthcare levels may
      provide valuable data on CKD epidemiology including changes in aetiology. Primary
      healthcare practitioners are faced with advanced CKD patients in resource-poor
      settings, with limited opportunity for upward referral hence the need for
      nephrology outreach programs.

PMID- 24731301
TI  - CASINO: surgical or nonsurgical treatment for cervical radiculopathy, a
      randomised controlled trial.
AB  - BACKGROUND: Cervical radicular syndrome (CRS) due to a herniated disc can be
      safely treated by surgical decompression of the spinal root. In the vast majority
      of cases this relieves pain in the arm and restores function. However,
      conservative treatment also has a high chance on relieving symptoms. The
      objective of the present study is to evaluate the (cost-) effectiveness of
      surgery versus prolonged conservative care during one year of follow-up, and to
      evaluate the timing of surgery. Predisposing factors in favour of one of the two
      treatments will be evaluated. METHODS/DESIGN: Patients with disabling radicular
      arm pain, suffering for at least 2 months, and an MRI-proven herniated cervical
      disc will be randomised to receive either surgery or prolonged conservative care
      with surgery if needed. The surgical intervention will be an anterior discectomy
      or a posterior foraminotomy that is carried out according to usual care. Surgery
      will take place within 2-4 weeks after randomisation. Conservative care starts
      immediately after randomisation. The primary outcome measure is the VAS for pain
      or tingling sensations in the arm one year after randomisation. In addition,
      timing of surgery will be studied by correlating the primary outcome to the
      duration of symptoms. Secondary outcome measures encompass quality of life, costs
      and perceived recovery. Predefined prognostic factors will be evaluated. The
      total follow-up period will cover two years. A sample size of 400 patients is
      needed. Statistical analysis will be performed using a linear mixed model which
      will be based on the 'intention to treat' principle. In addition, a new CRS
      questionnaire for patients will be developed, the Leiden Cervical Radicular
      Syndrome Functioning (LCRSF) scale. DISCUSSION: The outcome will contribute to
      better decision making for the treatment of cervical radicular syndrome. TRIAL
      REGISTRATION: NTR3504.

PMID- 24731302
TI  - A novel anti-CD19 monoclonal antibody (GBR 401) with high killing activity
      against B cell malignancies.
AB  - BACKGROUND: CD19 is a B cell lineage specific surface receptor whose broad
      expression, from pro-B cells to early plasma cells, makes it an attractive target
      for the immunotherapy of B cell malignancies. In this study we present the
      generation of a novel humanized anti-CD19 monoclonal antibody (mAb), GBR 401, and
      investigate its therapeutic potential on human B cell malignancies. METHODS: GBR
      401 was partially defucosylated in order to enhance its cytotoxic function. We
      analyzed the in vitro depleting effects of GBR 401 against B cell lines and
      primary malignant B cells from patients in the presence or in absence of purified
      NK cells isolated from healthy donors. In vivo, the antibody dependent cellular
      cytotoxicity (ADCC) efficacy of GBR 401 was assessed in a B cell depletion model
      consisting of SCID mice injected with healthy human donor PBMC, and a malignant B
      cell depletion model where SCID mice are xenografted with both primary human B
      CLL tumors and heterologous human NK cells. Furthermore, the anti-tumor activity
      of GBR 401 was also evaluated in a xenochimeric mouse model of human Burkitt
      lymphoma using mice xenografted intravenously with Raji cells. Pharmacological
      inhibition tests were used to characterize the mechanism of the cell death
      induced by GBR 401. RESULTS: GBR 401 exerts a potent in vitro and in vivo
      cytotoxic activity against primary samples from patients representing various B
      cell malignancies. GBR 401 elicits a markedly higher level of ADCC on primary
      malignant B cells when compared to fucosylated similar mAb and to Rituximab, the
      current anti-CD20 mAb standard immunotherapeutic treatment for B cell
      malignancies, showing killing at 500 times lower concentrations. Of interest, GBR
      401 also exhibits a potent direct killing effect in different malignant B cell
      lines that involves homotypic aggregation mediated by actin relocalization.
      CONCLUSION: These results contribute to consolidate clinical interest in
      developing GBR 401 for treatment of hematopoietic B cell malignancies,
      particularly for patients refractory to anti-CD20 mAb therapies.

PMID- 24731303
TI  - Influence of body mass index and periprostatic fat on rectal dosimetry in
      permanent seed prostate brachytherapy.
AB  - PURPOSE: We examined the influence of body mass index (BMI) and body fat
      distribution on rectal dose in patients treated with permanent seed brachytherapy
      for localized prostate cancer. METHODS AND MATERIALS: We analyzed 213 patients
      treated with I125 seed brachytherapy for localized prostate cancer. BMI and
      rectal dosimetry data for all patients were available. Data on visceral and
      subcutaneous fat distribution at the level of the iliac crest (n = 140) as well
      as the distribution of periprostatic and subcutaneous fat at the symphysis pubis
      level were obtained (n = 117). Fat distribution was manually contoured on CT on
      day 30 after brachytherapy. The correlation between BMI, fat distribution and
      rectal dose (R100 (in cc), R150 (cc), D2 (Gy)) was analyzed using the Spearman
      correlation coefficient. Differences in rectal dose between tertiles of body fat
      distribution were calculated using nonparametric tests. RESULTS: Periprostatic
      adipose was only weakly correlated with BMI (r = 0.0.245, p = 0.008) and only
      weakly correlated with the other fat measurements (r = 0.31-0.37, p < 0.001). On
      the other hand, BMI was correlated with all other fat measurements (>=0.58, p <
      0.001). All the other fat measurements were strongly correlated with each other
      (r = 0.5-0.87, p < 0.001). Patients with an R100 of >1.3 cc (23% of patients) had
      less visceral fat (p = 0.004), less subcutaneous fat at the level of the iliac
      crest (p = 0.046) and a lower BMI (26.8 kg/m2 vs. 28.5 kg/m2, p = 0.02) than
      patients with an R100 of <1.3 cc. Results were very similar when comparing an
      R100 of >1.0 cc (34% of patients) across the tertiles. None of the tested linear
      regression models were predictive (max 12%) of dose to the rectum. CONCLUSION:
      Dose to the rectum is dependent on BMI and body fat distribution. Periprostatic
      fat does not influence rectal dose. Dose to the rectum remains difficult to
      predict and depends on many factors, one of which is body fat distribution.

PMID- 24731304
TI  - Quality improvements in diabetes care, how holistic have they been? A case-study
      from the United Kingdom.
AB  - AIMS: As quality in diabetes care includes patient centred support for self
      management, investigating patients' experiences upon diagnosis can help improve
      access to this element of care among diverse populations. This research explored
      this care in the context of recent national quality improvement initiatives which
      support self-management. METHODS: South Asian and White European patients over 16
      years with a recent (< 1 year) diagnosis of diabetes were recruited from 18
      General Practitioner (GP) practices in three UK locations--Luton, West London and
      Leicester. A semi-structured qualitative interview was conducted with 47
      patients. RESULTS: Twenty one out of 47 (45%) reported unmet support and
      information needs at diagnosis. Although there was a small proportion of
      participants (8 out of 47, 17% of all respondents) who felt they did not require
      any help or support with managing their diabetes because their GP had provided
      comprehensive and efficient care, there was an equal number who voiced a negative
      view of the care they had received to date. This concerned information giving,
      support and communication, suggesting that recently implemented national quality
      improvement interventions may not have been successful in improving all aspects
      of diabetes care, particularly those encouraging self-management. The emerging
      analysis led to consideration of concordance as an important concept through
      which to understand inequalities and improve access to quality diabetes care. In
      order to encourage self-management from the start, care providers need to be
      cognisant that patients are not homogeneous and be responsive to their different
      information needs and emotional responses to diagnosis. CONCLUSIONS: In order to
      support self-management and deliver patient centred care in diverse populations,
      care providers will need to be adaptable to individual needs around diagnosis.

PMID- 24731305
TI  - Paired measurement of urinary creatinine in neonates based on a Jaffe and an
      enzymatic IDMS-traceable assay.
AB  - BACKGROUND: Urinary creatinine can be quantified by Jaffe or enzymatic assays and
      is commonly used as denominator of urinary excretion of electrolytes or protein.
      Paired analysis in pediatric and adult samples documented inter-assay differences
      (up to 80%). We verified the interchangeability of two IDMS-traceable assays
      (Jaffe and enzymatic) for neonatal urine and report on neonatal urinary
      creatinine values using these IDMS-traceable methods. METHODS: Creatinine was
      measured in 84 neonatal urine samples from 46 neonates by an IDMS traceable Jaffe
      and enzymatic assay (Roche Diagnostics, Cobas c702 module). Creatinine values,
      differences in urinary creatinine and clinical characteristics were described and
      covariates of between assay difference were explored (Wilcoxon, Bland-Altman,
      correlation, multiple regression). RESULTS: Median Jaffe and enzymatic urinary
      creatinine concentrations were 9.25 (range 3.7-42.2) and 9.15 (range 3.8-42.9)
      mg/dL respectively, resulting in a median difference of 0.08 (SD 0.6, range -2.4
      to 0.96) mg/dL. In a multiple regression model, urinary enzymatic creatinine
      concentration (r = 0.45) and postnatal age (r = -0.59) remained independent
      variables of the difference between both assays (r2 adj = 0.45). CONCLUSIONS: The
      tested IDMS-traceable assays showed interchangeable in heterogeneous neonatal
      urine samples. Using these assays, neonatal urinary creatinine showed 5-20 fold
      lower values than those observed in children or adults with a significant
      negative correlation with postnatal age.

PMID- 24731306
TI  - Developing a rapid and sensitive method for determination of trans-fatty acids in
      edible oils using middle-infrared spectroscopy.
AB  - Several countries have adopted labelling policy concerning the declaration of
      trans fatty acids (TFAs) content in the nutritional facts panel of processed
      food. Consequently, the food industry requires rapid methods to measure low
      levels of TFAs. This paper reports the development of a rapid method to determine
      TFAs <1% in edible oils (palm, peanut, soybean and sunflower) and oils/fat
      samples extracted from finished products using attenuated total reflection
      Fourier transform infrared spectroscopy (ATR-FTIR). Traditional linear regression
      and Partial Least Squares (PLS) statistical tools were applied to model the
      spectroscopic data. The calibration models of edible oils/fat samples showed a
      coefficient-of-correlation ?0.982 and standard error of prediction (SEP) between
      0.03% and 0.06%. The ATR-FTIR results of extracted oils/fat are in good agreement
      with the capillary gas chromatography with flame ionisation detector (GC/FID).
      This study has demonstrated that ATR-FTIR technique can be used to rapidly
      determine trans fatty acids <1% in oils/fat. 

PMID- 24731307
TI  - A rapid and simple determination of caffeine in teas, coffees and eight
      beverages.
AB  - Caffeine was extracted and preconcentrated by the simple, fast and green method
      of dispersive liquid-liquid microextraction (DLLME) and analysed by gas
      chromatography-nitrogen phosphorus detection (GC-NPD). The influence of main
      parameters affecting the extraction efficiency investigated and optimised. Under
      the optimal conditions, the method was successfully applied to determination of
      caffeine in different real samples including five types of tea (green, black,
      white, oolong teas and tea bag), two kinds of coffee (Nescafe coffee and coffee),
      and eight beverages (regular Coca Cola, Coca Cola zero, regular Pepsi, Pepsi max,
      Sprite, 7up, Red Bull and Hype).The limit of detection (LOD) and limit of
      quantification (LOQ) were 0.02 and 0.05 MUg mL(-1), respectively. Linear dynamic
      range (LDR) was 0.05-500 MUg mL(-1) and determination coefficient (R(2)) was
      0.9990. The relative standard deviation (RSD) was 3.2% (n=5, C=1 MUg mL(-1)).

PMID- 24731308
TI  - The use of tetragonal star-like polyaniline nanostructures for efficient solid
      phase extraction and trace detection of Pb(II) and Cu(II) in agricultural
      products, sea foods, and water samples.
AB  - Due to importance of trace analysis of lead and copper ions because of their
      toxicity, in this paper, for the first time a unique tetragonal star-like
      morphology of polyaniline was applied as a efficient solid phase for selective
      trace separation of copper and lead at optimum experimental conditions in shrimp,
      fish and water samples. Due to the unique star like nanostructure of synthesized
      sorbent, the tendency of the sorbent toward selective extraction of lead and
      copper ion in the optimised pH is very interesting. The prepared polymeric resin
      displayed good figures of merits with analytical calibration curve ranging from 1
      to 120 MUg L(-1) for copper and 2 to 100 MUg L(-1) for lead ions with limits of
      detection of 0.4 MUg L(-1) for copper and 0.9 MUg L(-1) for lead, adsorption
      capacities of 84 and 110 mg g(-1) for copper and lead ions, respectively,
      extraction efficiency of greater than 96%, and relative standard deviation (RSD)
      of less than 4% for eight separate column experiments in determination of 5.0 MUg
      of lead and copper. The obtained data for adsorption capacity of the sorbent
      shows the high tendency of the sorbent toward the mentioned ions in this
      nanostructure form. Finally, this sorbent can be used as a simple, rapid,
      reliable, selective and sensitive method for determination of trace levels of
      Cu(II) and Pb(II).

PMID- 24731309
TI  - Straightforward rapid spectrophotometric quantification of total cyanogenic
      glycosides in fresh and processed cassava products.
AB  - In this study, we extend pioneering studies and demonstrate straightforward
      applicability of the corrin-based chemosensor, aquacyanocobyrinic acid (ACCA),
      for the instantaneous detection and rapid quantification of endogenous cyanide in
      fresh and processed cassava roots. Hydrolytically liberated endogenous cyanide
      from cyanogenic glycosides (CNp) reacts with ACCA to form dicyanocobyrinic acid
      (DCCA), accompanied by a change of colour from orange to violet. The method was
      successfully tested on various cassava samples containing between 6 and 200 mg
      equiv. HCN/kg as verified with isonicotinate/1,3-dimethylbarbiturate as an
      independent method. The affinity of ACCA sensor to cyanide is high, coordination
      occurs fast and the colorimetric response can therefore be instantaneously
      monitored with spectrophotometric methods. Direct applications of the sensor
      without need of extensive and laborious extraction processes are demonstrated in
      water-extracted samples, in acid-extracted samples, and directly on juice drops.
      ACCA showed high precision with a standard deviation (STDV) between 0.03 and 0.06
      and high accuracy (93-96%). Overall, the ACCA procedure is straightforward, safe
      and easily performed. In a proof-of-concept study, rapid screening of ten samples
      within 20 min has been tested.

PMID- 24731310
TI  - Determination of polyphenolic compounds of red wines by UV-VIS-NIR spectroscopy
      and chemometrics tools.
AB  - Spectral analysis is a quick and non-destructive method to analyse wine. In this
      work, trans-resveratrol, oenin, malvin, catechin, epicatechin, quercetin and
      syringic acid were determined in commercial red wines from DO Rias Baixas and DO
      Ribeira Sacra (Spain) by UV-VIS-NIR spectroscopy. Calibration models were
      developed using principal component regression (PCR) or partial least squares
      (PLS) regression. HPLC was used as reference method. The results showed that
      reliable PLS models were obtained to quantify all polyphenols for Rias Baixas
      wines. For Ribeira Sacra, feasible models were obtained to determine quercetin,
      epicatechin, oenin and syringic acid. PCR calibration models showed worst
      reliable of prediction than PLS models. For red wines from mencia grapes,
      feasible models were obtained for catechin and oenin, regardless the geographical
      origin. The results obtained demonstrate that UV-VIS-NIR spectroscopy can be used
      to determine individual polyphenolic compounds in red wines. 

PMID- 24731311
TI  - Xanthophyll content of selected vegetables commonly consumed in the Philippines
      and the effect of boiling.
AB  - The purpose of this study was to quantify xanthophylls in selected vegetables
      commonly consumed in the Philippines and to investigate the effect of boiling on
      their availability. Thirteen vegetables were grouped into green-leafy and non
      leafy. Results showed that fresh malunggay contains the highest amount of lutein
      (167.1+/-6.1 MUg/g), neoxanthin (48.66+/-2.31 MUg/g), and violaxanthin (37.86+/
      1.76 MUg/g) while mais has the highest zeaxanthin (269.1+/-11.8 MUg/g).
      Statistically, there is no significant difference (p>0.1) in xanthophyll content
      between fresh leafy and non-leafy samples. However, 15-min boiling (100  degrees
      C) changed this, resulting in a significant difference (p<0.1) in xanthophyll
      content between the two groups. Boiling increased the availability of lutein and
      neoxanthin, while an opposite effect was observed for zeaxanthin and
      violaxanthin. Results also showed that consuming 20 g of cooked malunggay
      (Moringa oleifera) can provide 100% the recommended level of lutein (10 mg) for
      eye health, while 8 g of cooked mais (Zea mays) a day can provide a high enough
      level (2 mg) of zeaxanthin.

PMID- 24731312
TI  - An effective strategy to develop active cinnamic acid-directed antioxidants based
      on elongating the conjugated chains.
AB  - To optimize antioxidant activity and lipophilicity of cinnamic acid derivatives
      (CAs) including ferulic acid, sinapic acid, 3,4-dimethoxycinnamic acid, and p
      hydroxycinnamic acid, four analogs bearing an additional double bond between
      their aromatic ring and propenoic acid moiety were designed and synthesized based
      on the conjugated chain elongation strategy. The antioxidant performance of the
      CAs were investigated by 2,2'-diphenyl-1-picrylhydrazyl (DPPH)-scavenging, ferric
      reducing/antioxidant power, cyclic voltammetry, DNA strand breakage-inhibiting
      and anti-haemolysis activity assays. It was found that CAs with elongation of
      conjugated chains display increased DPPH-scavenging, DNA strand breakage
      inhibiting and anti-haemolysis activities as compared to their parent molecules,
      due to their improved hydrogen atom-donating ability and lipophilicity. Overall,
      this work highlights an effective strategy to develop potential CA-directed
      antioxidants by elongating their conjugated chain. 

PMID- 24731313
TI  - Relationships of flour solvent retention capacity, secondary structure and
      rheological properties with the cookie making characteristics of wheat cultivars.
AB  - The relationships of grain, flour solvent retention capacity (SRC) and dough
      rheological properties with the cookie making properties of wheat cultivars were
      evaluated. Cultivars with higher proportion of intermolecular-beta
      sheets+antiparallel beta sheets and lower alpha-helix had greater gluten
      strength. The grain weight and diameter positively correlated with the proportion
      of fine particles and the cookie spread factor (SF) and negatively to the grain
      hardness (GH) and Na2CO3 SRC. The SF was higher in the flour with a higher amount
      of fine particle and with a lower Na2CO3 SRC and dough stability (DS). The
      breaking strength (BS) of cookies was positively correlated to lactic acid (LA)
      SRC, DS, peak time, sedimentation value (SV), G' and G". Na2CO3 SRC and GH were
      strongly correlated. The gluten performance index showed a strong positive
      correlation with SV, DS, G' and G". The water absorption had a significant
      positive correlation with sucrose SRC and LASRC. Cultivars with higher GH
      produced higher amount of coarse particles in flours that had higher Na2CO3 SRC
      and lower cookie SF. 

PMID- 24731314
TI  - Ultrasensitive and simultaneous determination of twenty-one amino acids and
      amines in culture media, red wine and beer.
AB  - Ultrasensitive and simultaneous determination of amino acids and amines (AAs) in
      media and winemaking products is very important for evaluating the relationship
      profile between the depletion of AAs and aroma compounds formation. In this work,
      by combing the advantages of Taguchi's scheme with Pareto graphs and Range
      analysis pattern, an analytical method with efficiently improving fluorescence
      intensity and resolutions of AAs while saving the time and resources is developed
      to simultaneously and ultrasensitively detect 21 AAs in media, wine and beer. The
      results indicate the detection limit (DL) could be reached at ng L(-1) level
      (3.34-284.3 ng L(-1)), which is 10(6) higher than that of DL obtained by general
      method. Furthermore, the linear ranges are also established so that the proposed
      method could be accurately applied. These results demonstrate the method provides
      an easy and effective way to ultrasensitively and simultaneously analyse AAs in
      complex products.

PMID- 24731315
TI  - beta-Lactoglobulin heat-induced aggregates as carriers of polyunsaturated fatty
      acids.
AB  - The aim of this work was to obtain heat-induced beta-lactoglobulin (BLG)
      aggregates in order to test them as carriers of a model polyunsaturated fatty
      acid (PUFA), linoleic acid (LA). BLG aggregates were obtained at 85  degrees C by
      varying the heating time (0-60 min) and pH of protein dispersion (6.5-7.5).
      Aggregates were characterised by intrinsic and extrinsic fluorescence and surface
      hydrophobicity (S0). Binding experiments were conducted by fluorescence
      spectroscopy. Results showed increased BLG aggregate S0 values which could
      strongly depend on the pH of aggregate formation. Aggregates obtained at pH 6.5
      showed the greatest S0 values, so they could find application as LA carriers.
      Nevertheless, conjugation of LA to BLG aggregates showed complex behaviour
      depending on the aggregate producing conditions (pH, heating time and/or
      combination). The LA binding properties of BLG aggregates were not linked to
      their hydrophobic characteristics, suggesting that conjugation could require the
      structural preservation of the LA binding site.

PMID- 24731316
TI  - Decoction, infusion and hydroalcoholic extract of Origanum vulgare L.: different
      performances regarding bioactivity and phenolic compounds.
AB  - Bioactivity of oregano methanolic extracts and essential oils is well known.
      Nonetheless, reports using aqueous extracts are scarce, mainly decoction or
      infusion preparations used for therapeutic applications. Herein, the antioxidant
      and antibacterial activities, and phenolic compounds of the infusion, decoction
      and hydroalcoholic extract of oregano were evaluated and compared. The
      antioxidant activity is related with phenolic compounds, mostly flavonoids, since
      decoction presented the highest concentration of flavonoids and total phenolic
      compounds, followed by infusion and hydroalcoholic extract. The samples were
      effective against gram-negative and gram-positive bacteria. It is important to
      address that the hydroalcoholic extract showed the highest efficacy against
      Escherichia coli. This study demonstrates that the decoction could be used for
      antioxidant purposes, while the hydroalcoholic extract could be incorporated in
      formulations for antimicrobial features. Moreover, the use of infusion/decoction
      can avoid the toxic effects showed by oregano essential oil, widely reported for
      its antioxidant and antimicrobial properties. 

PMID- 24731317
TI  - A facial electrochemical approach to determinate bisphenol A based on graphene
      hypercrosslinked resin MN202 composite.
AB  - It first reported a novel electrochemical approach for the in situ determination
      of bisphenol A (BPA) in the milk and mineralised water using graphene
      hypercrosslinked resin MN202 composite (MN202) modified electrode. The
      electrocatalytic oxidation and electroanalytical of BPA on the modified electrode
      were investigated by cyclic voltammetry (CV) and differential pulse voltammetry
      (DPV). It is notable that the oxidation peak current of BPA had enhanced
      remarkably and the oxidation overpotential had decreased significantly.
      Experimental parameters, such as the accumulation potential and time, scan rate,
      and the pH value of buffer solution were optimised. Under the optimised
      conditions, the oxidation peak current was proportional to BPA concentration in a
      wide range between 0.005 and 20.0 MUmol/L, and the detection limit was 1.02
      nmol/L (S/N=3). Moreover, the fabricated electrode also exhibited good
      reproducibility and stability, and employed to in situ determinate BPA in milk
      and mineralised water successfully.

PMID- 24731318
TI  - Free amino acid profiling in the giant puffball mushroom (Calvatia gigantea)
      using UPLC-MS/MS.
AB  - Wild edible and medicinal mushroom, Calvatia gigantea, was quantitatively
      analyzed for the determination of its free amino acids using ultra performance
      liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). The concentrations
      of total free amino acids, essential and non-essential amino acids were 199.65
      mg/100 g, 113.69 mg/100 g, and 85.96 mg/100 g in C. gigantea, respectively. This
      study showed that C. gigantea, so called a giant puffball mushroom, has free
      amino acids content. The essential amino acids: tryptophan, isoleucine, valine,
      phenylalanine, leucine, threonine, lysine, histidine, methionine, and the non
      essential amino acids: tyrosine, 4-hyrdroxy proline, arginine, proline, glycine,
      serine, alanine, glutamine, glutamic acid, aspargine, aspartic acid were
      detected.

PMID- 24731320
TI  - Characteristic fingerprint based on gingerol derivative analysis for
      discrimination of ginger (Zingiber officinale) according to geographical origin
      using HPLC-DAD combined with chemometrics.
AB  - Chromatographic fingerprints of gingers from five different ginger-producing
      countries (China, India, Malaysia, Thailand and Vietnam) were newly established
      to discriminate the origin of ginger. The pungent bioactive principles of ginger,
      gingerols and six other gingerol-related compounds were determined and
      identified. Their variations in HPLC profiles create the characteristic pattern
      of each origin by employing similarity analysis, hierarchical cluster analysis
      (HCA), principal component analysis (PCA) and linear discriminant analysis (LDA).
      As results, the ginger profiles tended to be grouped and separated on the basis
      of the geographical closeness of the countries of origin. An effective
      mathematical model with high predictive ability was obtained and chemical markers
      for each origin were also identified as the characteristic active compounds to
      differentiate the ginger origin. The proposed method is useful for quality
      control of ginger in case of origin labelling and to assess food authenticity
      issues. 

PMID- 24731319
TI  - Potential of spectroscopic techniques and chemometric analysis for rapid
      measurement of docosahexaenoic acid and eicosapentaenoic acid in algal oil.
AB  - Developing rapid methods for measuring long-chain omega-3 (n-3) poly-unsaturated
      fatty acid (LCPUFA) contents has been a crucial request from the algal oil
      industry. In this study, four spectroscopy techniques, namely visible and short
      wave near infra-red (Vis-SNIR), long-wave near infra-red (LNIR), mid-infra-red
      (MIR) and nuclear magnetic resonance (NMR) spectroscopy, were exploited for
      determining the docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA)
      contents in algal oil. The best prediction for both DHA and EPA were achieved by
      NMR spectroscopy, in which the determination coefficients of cross-validation
      (rCV(2)) values were 0.963 and 0.967 for two LCPUFAs. The performances of Vis
      SNIR and LNIR spectroscopy were also accepted. The variable selection was proved
      as an efficient and necessary step for the spectral analysis in this study. The
      results were promising and implied that spectroscopy techniques have a great
      potential for assessment of DHA and EPA in algal oil.

PMID- 24731321
TI  - Use of modified wheat bran for the removal of chromium(VI) from aqueous
      solutions.
AB  - Novel adsorbents, wheat bran (WB) and modified wheat bran (M-WB) with tartaric
      acid were developed and Cr(VI) adsorption was investigated by changing various
      parameters. The adsorption increased with contact time and become optimum at 180
      min for WB and 200 min for M-WB. When the pH of the solution phase increased,
      some of toxic Cr(VI) reduced into less toxic Cr(III) on the WB surface. The
      maximum removal of Cr(VI) from the solution having an initial Cr(VI)
      concentration of 200 mg L(-1) was obtained at pH 2.0 as 51.0% and 90.0% for WB
      and M-WB, respectively. Isotherm data of Cr(VI) adsorption on WB and M-WB was
      described by the Freundlich adsorption model. The adsorption capacity of 4.53 mg
      of Cr(VI)/g for WB and 5.28 mg of Cr(VI)/g for M-WB was obtained at pH 2 and 2.2
      respectively.

PMID- 24731322
TI  - Quantification of bio- and techno-functional peptides in tryptic bovine micellar
      casein and beta-casein hydrolysates.
AB  - Numerous peptides generated by triptic hydrolysis of micellar casein and beta
      casein from bovine milk have been reported to exhibit bio-functional or techno
      functional activities. In this study, the focus was placed on the quantification
      of eleven potential functional peptides generated by enzymatic hydrolysis with
      trypsin. The identity of the target peptides was verified by LC-ESI-MS/MS and a
      reverse phase high performance liquid chromatography method (RP-HPLC) was
      established to quantify the peptides. The quantification was based on calibration
      curves drawn using synthesised purified peptides. The regression analysis
      comparing >30 standard measurements of each peptide standard showed a regression
      coefficient R(2)>0.9958. The inter-day repeatability of the quantification method
      was always within a relative error of 0.2-6.5%, while the relative error of the
      accuracy for reproducibility was in the range of 0.1-2.4%. The established method
      was successfully applied for the quantitative analysis of the eleven functional
      peptides in different dairy fractions generated by cross-flow ultrafiltration. 

PMID- 24731323
TI  - A new strategy for determination of bisphenol A in the presence of Sudan I using
      a ZnO/CNTs/ionic liquid paste electrode in food samples.
AB  - The electrochemistry of bisphenol A (BPA) was studied by voltammetric methods at
      a surface of carbon paste electrode modified by a ZnO/CNTs nanocomposite and room
      temperature ionic liquid of 1,3-dipropylimidazolium bromide. The ratio of
      ZnO/CNTs and ionic liquid (IL) on the surface of the electrode has to be
      controlled carefully because the charging currents. The anodic peaks of BPA and
      Sudan I in their mixture can be well separated. At pH 7.0 the two peaks are
      separated ca. 0.47 and 0.70 V, respectively; hence BPA can be determined in the
      presence of Sudan I and more than 8.7 times current excess of BPA. The peaks
      current of square wave voltammograms (SWV) of BPA and Sudan I increased linearly
      with their concentration in the ranges of 0.002-700 MUmol L(-1)BPA and 0.2-800
      MUmol L(-1) Sudan I. The detection limits for BPA and Sudan I were 9.0 nmol L(-1)
      and 80 nmol L(-1), respectively. The modified electrode has been successfully
      applied for the assay of BPA in food samples. This study provides a simple and
      easy approach to selectively detect BPA in the presence of Sudan I.

PMID- 24731324
TI  - Multivariate statistical analysis treatment of DSC thermal properties for animal
      fat adulteration.
AB  - The adulteration of edible fats is a kind of fraud that impairs the physical and
      chemical features of the original lipid materials. It has been detected in
      various food, pharmaceutical and cosmeceutical products. Differential scanning
      calorimetry (DSC) is the robust thermo-analytical machine that permits to
      fingerprint the primary crystallisation of triacylglycerols (TAGs) molecules and
      their transition behaviours. The aims of this study was to assess the cross
      contamination caused by lard concentration of 0.5-5% in the mixture systems
      containing beef tallow (BT) and chicken fat (CF) separately. TAGs species of pure
      and adulterated lipids in relation to their crystallisation and melting
      parameters were studied using principal components analysis (PCA). The results
      showed that by using the heating profiles the discrimination of LD from BT and CF
      was very clear even at low dose of less than 1%. Same observation was depicted
      from the crystallisation profiles of BT adulterated by LD doses ranging from 0.1%
      to 1% and from 2% to 5%, respectively. Furthermore, CF adulterated with LD did
      not exhibit clear changes on its crystallisation profiles. Consequently, DSC
      coupled with PCA is one of the techniques that might use to monitor and
      differentiate the minimum adulteration levels caused by LD in different animal
      fats. 

PMID- 24731325
TI  - Metabolite profiling of polyphenols in peels of Citrus limetta Risso by
      combination of preparative high-speed countercurrent chromatography and LC-ESI
      MS/MS.
AB  - The polar constituents of peels from Citrus limetta variety Risso (Rutaceae) were
      investigated by a combination of two complementary chromatographic techniques
      consisting of preparative high-speed countercurrent chromatography (HSCCC), and
      off-line LC-ESI-MS/MS analysis to design a two-dimensional metabolite profile.
      Countercurrent chromatography (CCC) using solely immiscible solvent systems
      allowed the fractionation of principal components and an enrichment of minor
      concentrated metabolites from a crude polar solvent partition of C. limetta peels
      for subsequent structural identification by LC-ESI-MS/MS analysis. The
      combination of two very different chromatographic techniques resulted in lower
      detection limits for electrospray mass-spectrometry and revealed eighty-five
      compounds, including three abscisic acid derivatives, five limonoid glycosides,
      twenty-six dihydro-cinnamic and cinnamic acid glycosides, eleven flavanone
      glycosides, seven flavone glycosides, seventeen flavonol glycosides, including
      limocitrol and limocitrin derivatives. As a chemocharacteristic for C. limetta
      metabolites, many of the detected structures were linked to single and multiple 3
      hydroxy-3-methyl-glutaryl (HMG) substitutions. C. limetta peels are a by-product
      of juice production, and not only the antioxidant fractions but also some of the
      fortified compounds could be used for food and pharmaceutical purposes. 

PMID- 24731326
TI  - QuEChERS GC-MS validation and monitoring of pesticide residues in different foods
      in the tomato classification group.
AB  - The objective of this study was to validate (SANCO/12495/2011 and NTC-ISO/IEC
      17025) multi-residue multi-class methods using QuEChERS sample preparation and GC
      MS for the analysis of regulated pesticides in tomatoes (Solanum lycopersicum),
      tamarillos (Solanum betaceum) and goldenberries (Physalis peruviana). These Latin
      American products are representative and widely produced in Antioquia (Colombia).
      Sample preparation followed the UNE-EN 15662 method (150 mg MgSO4, 25mg primary
      secondary amines and 25mg of octadecylsiloxane for cleanup; graphitized carbon
      black was added for tomatoes). Extracts were injected using a programmed
      temperature-vaporizing injector. The residues were validated over a range from
      0.02 mg/kg to 0.20 mg/kg, with 24 analytes validated in tomatoes, 33 in
      tamarillos and 28 in goldenberries. An initial risk assessment was enabled by
      monitoring 24 samples in the municipalities of El Penol, Marinilla and San
      Vicente Ferrer. Risks were found for tomatoes, but no significant risks were
      found for tamarillos or goldenberries.

PMID- 24731327
TI  - Seafood-like flavour obtained from the enzymatic hydrolysis of the protein by
      products of seaweed (Gracilaria sp.).
AB  - An enzymatic bromelain seaweed protein hydrolysate (eb-SWPH) was characterised as
      the precursor for thermally processed seafood flavour. Seaweed (Gracilaria
      fisheri) protein after agar extraction was hydrolysed using bromelain (enzyme
      activity=119,325 U/g) at 0-20% (w/w) for 0.5-24 h. Optimal hydrolysis conditions
      were determined using response surface methodology. The proposed model took into
      account the interaction effect of the enzyme concentration and hydrolysis time on
      the physicochemical properties and volatile components of eb-SWPH. The optimal
      hydrolysis conditions for the production of eb-SWPH were 10% bromelain for 3h,
      which resulted in a 38.15% yield and a 62.91% degree of hydrolysis value. Three
      free amino acids, arginine, lysine, and leucine, were abundant in the best
      hydrolysate. Ten volatile flavours of the best eb-SWPH were identified using gas
      chromatography/mass spectrometry. The predominant odourants were hexanal,
      hexanoic acid, nonanoic acid, and dihydroactinidiolide. The thermally processed
      seafood flavour produced from eb-SWPH exhibited a roasted seafood-like
      flavouring.

PMID- 24731328
TI  - A simple and feasible approach to purify konjac glucomannan from konjac flour-
      temperature effect.
AB  - A simple one-step purification process was provided to extract KGM from KF by
      phase separation. The results showed that appropriate temperature control was a
      key factor and the products were inodorous, colourless and of high purity at the
      optimal temperature 68  degrees C. In this purification, soluble sugar and starch
      of extracted KGM were nearly clearly reduced and up to 95%, 80% (T68) of protein
      and ash were removed, respectively as compared with KF. Odour and transparency
      were improved 4 ranks and 30%, respectively. Besides, the etaapp reached 42.30 Pa
      s and increased by 93.55% as compared, which could stay at a steady level for a
      week. Furthermore, morphology of extracted KGM displayed regular lamellar and
      wrinkling distribution for removed impurities. The temperature-controlled method
      not only enriches the knowledge of KGM purification but also has the potential to
      broaden the application of KGM.

PMID- 24731329
TI  - An optimized ultrasound-assisted extraction and simultaneous quantification of 26
      characteristic components with four structure types in functional foods from
      ginkgo seeds.
AB  - An optimized method of ultrasound-assisted extraction followed by ultra-high
      performance liquid chromatography coupled with triple-quadrupole tandem mass
      spectrometry (UAE-UHPLC-TQ/MS(2)) was proposed for the simultaneous extraction
      and determination of 26 characteristic components covering four structure types
      (flavonoids, terpene lactones, ginkgolic acids and phenylpropanols) in ginkgo
      seeds (GSs). The UAE parameters (ultrasound power, time and solvent-to-material
      ratio) were optimized using a response surface methodology. This is the first
      report of the simultaneous analysis of 26 compounds in Ginkgo biloba using UHPLC
      TQ/MS(2); this analysis afforded good linearity, precision, repeatability and
      accuracy. UAE-UHPLC-TQ/MS(2) was successfully applied to ginkgo seed samples, and
      the analysis showed that GSs are rich in terpene lactones and could be selected
      as a healthy food resource. The results suggest that UAE-UHPLC-TQ/MS(2) might be
      able to be utilized as a tool for the quality assessment of samples from GSs or
      other related products using flavonoids, terpene lactones, ginkgolic acids and
      phenylpropanols as markers. 

PMID- 24731330
TI  - Preparation of high purity egg phosvitin using anion exchange chromatography.
AB  - Egg yolk phosvitin serves as a warehouse to provide metal ions for embryo
      development. It is significant for mineral metabolism study and also of great
      potential to be developed into functional foods with mineral absorption promoting
      ability. In this study, phosvitin was first extracted from yolk granules using
      10% NaCl, dialysed and then adjusted to various pHs to remove impurities. The
      purity of phosvitin extracts was increased from 54.5% to 63.7% at decreasing pH
      from 8.0 to 5.5, and started to decrease afterwards. Both the yield and recovery
      were significantly decreased at decreasing pHs, especially at pHs close to its pI
      (pH 4.0), indicating the occurrence of co-precipitation of phosvitin with HDL.
      The extract prepared at pH 8.0 showed the highest recovery of 82.7%; its purity
      was increased from 54.5% to 97.1% by anion exchange chromatography, with a
      recovery of 42.0%. This simple method could be scaled up for industrial
      production. 

PMID- 24731331
TI  - Purification and partial characterisation of a cathepsin L-like proteinase from
      sea cucumber (Stichopus japonicus) and its tissue distribution in body wall.
AB  - A cathepsin L-like proteinase (CLP) with molecular weight of 30.9 kDa from the
      gut of sea cucumber (Stichopus japonicas, S. japonicus) was isolated and purified
      to homogeneity by several chromatographic procedures. The enzyme exhibited
      optimum activity at pH 5.0-5.5 and 50  degrees C, and showed thermostability up
      to 40  degrees C. The enzyme activity was completely inhibited by Zn(2+),
      strongly inhibited by Fe(2+) and Cu(2+), drastically reduced by cysteine
      proteinase inhibitors, but slightly enhanced by thiol-activating agents. The
      enzyme efficiently hydrolysed the specific substrate of cathepsin L, but hardly
      hydrolysed the specific substrates for cathepsin B, cathepsin H and cathepsin K.
      Immunohistochemical studies indicated that the CLP was more abundant in the
      epidermis rather than in the dermis of S. japonicus body wall. The distribution
      of CLP showed positive correlation with autolysis rate. Therefore, the
      relationship between CLP and autolysis deserved further study.

PMID- 24731332
TI  - Determination of minor and trace elements in aromatic spices by micro-wave
      assisted digestion and inductively coupled plasma-mass spectrometry.
AB  - This study aimed at analyzing the concentrations of 23 minor and trace elements
      in aromatic spices by inductively coupled plasma-mass spectrometry (ICP-MS),
      after wet digestion by microwave system. The analytical method was validated by
      linearity, detection limits, precision, accuracy and recovery experiments,
      obtaining satisfactory values in all cases. Results indicated the presence of
      variable amounts of both minor and trace elements in the selected aromatic
      spices. Manganese was high in cinnamon (879.8 MUg/g) followed by cardamom (758.1
      MUg/g) and clove (649.9 MUg/g), strontium and zinc were high in ajwain (489.9
      MUg/g and 84.95 MUg/g, respectively), while copper was high in mango powder
      (77.68 MUg/g). On the whole some of the minor and essential trace elements were
      found to have good nutritional contribution in accordance to RDA. The levels of
      toxic trace elements, including As, Cd, and Pb were very low and did not found to
      pose any threat to consumers.

PMID- 24731333
TI  - Occurrence of inorganic arsenic in edible Shiitake (Lentinula edodes) products.
AB  - The present study reports arsenic speciation analysis in edible Shiitake
      (Lentinula edodes) products. The study focused on the extraction, and accurate
      quantification of inorganic arsenic (iAs), the most toxic form of arsenic, which
      was selectively separated and determined using anion exchange LC-ICPMS. A wide
      variety of edible Shiitake products (fresh mushrooms, food supplements, canned
      and dehydrated) were purchased and analysed. A cultivated Shiitake grown under
      controlled conditions was also analysed. The extraction method showed
      satisfactory extraction efficiencies (>90%) and column recoveries (>85%) for all
      samples. Arsenic speciation revealed that iAs was the major As compound up to
      1.38 mg As kg(-1) dm (with a mean percentage of 84% of the total arsenic) and
      other organoarsenicals were found as minor species. Shiitake products had high
      proportions of iAs and therefore should not be ignored as potential contributors
      to dietary iAs exposure in populations with a high intake of Shiitake products.

PMID- 24731334
TI  - Effect of seasonal variation on the composition and properties of raw milk
      destined for processing in the UK.
AB  - The composition and physical properties of raw milk from a commercial herd were
      studied over a 1 year period in order to understand how best to utilise milk for
      processing throughout the year. Protein and fat levels demonstrated seasonal
      trends, while minerals and many physical properties displayed considerable
      variations, which were apparently unrelated to season. However, rennet clotting
      time, ethanol stability and foaming ability were subject to seasonal variation.
      Many significant interrelationships in physico-chemical properties were found. It
      is clear that the milk supply may be more suited to the manufacture of different
      products at different times of the year or even on a day to day basis. Subsequent
      studies will report on variation in production and quality of products
      manufactured from the same milk samples described in the current study and will
      thus highlight potential advantages of seasonal processing of raw milk.

PMID- 24731335
TI  - Pre-anthesis CPPU low dosage application increases 'Hayward' kiwifruit weight
      without affecting the other qualitative and nutritional characteristics.
AB  - In 2008, in Central Italy, a low dosage of CPPU solution, 4 MUL L(-1) (6 hL/ha),
      was sprayed on the canopy of vines of 'Hayward' kiwifruit, at the "break of
      sepals", about one week before anthesis, to study its effects on fruit
      weight/size and on qualitative and nutritional characteristics. At harvest, CPPU,
      with respect to control, significantly increased the fresh weight by about 12%
      (+12.6 g fruit(-1)) and consequently the yield per vine, without affecting fruit
      shape, firmness, dry matter (%), total soluble solids, glucose, fructose,
      sucrose, starch, citrate, malate, vitamin C and soluble and insoluble oxalic
      acid. After 3 months of storage, CPPU-treated kiwifruits and the control fruit
      showed no difference in dry matter content, fruit firmness and total soluble
      solids. The results indicate that a low dosage of CPPU applied in pre-anthesis
      can improve fruit weight/size without any negative effect on fruit qualitative
      and nutritional characteristics.

PMID- 24731336
TI  - Efficient preparative isolation and identification of walnut bioactive components
      using high-speed counter-current chromatography and LC-ESI-IT-TOF-MS.
AB  - Preparative isolation of complex mixtures of compounds from walnut polar extracts
      was established by a combination of high-speed counter-current chromatography
      (HSCCC) and electrospray ionization-ion trap-time of flight mass spectrometry
      (ESI-IT-TOF-MS). Compounds were isolated after a solvent optimisation selection
      based on solute distribution in a biphasic solvent system. Isolation was achieved
      through one or two successive HSCCC runs, and final purification on Sephadex LH
      20. Isolated compounds included ellagitannins (1-11), gallic acid (12),
      dicarboxylic acid glucosides (13-15), hydrojuglone glucoside (16), catechin (17),
      procyanidin B2 (18), and megasterone glucosides (19-20). Praecoxin D (4) was
      isolated for the first time from walnut, while praecoxin A methyl ester (5) and
      glansreginin A n-butyl ester (14) are newly identified compounds. The purity and
      identity of isolated compounds were confirmed by NMR and HPLC-ESI-MS/MS. These
      results provided a foundation for in depth characterisation of walnut compounds
      and offered an efficient strategy for isolation of potentially health-relevant
      phytochemicals from walnuts. 

PMID- 24731337
TI  - Miniaturized graphene-based pipette tip extraction coupled with liquid
      chromatography for the determination of sulfonamide residues in bovine milk.
AB  - A miniaturized graphene-based pipette tip extraction (M-G-PTE) method coupled
      with liquid chromatography-ultraviolet detection was developed for rapid
      screening of sulfadimidine, sulfachloropyridazine, sulfamonomethoxine, and
      sulfachloropyrazine residues in bovine milk. Because of the large surface area
      and unique chemical structure of graphene, an M-G-PTE device packed with 3.0mg
      graphene could handle 2.0mL of milk samples at one time. This M-G-PTE device
      showed better adsorption performance for sulfonamides (SAs) than those packed
      with other adsorbents such as C18, HLB, SCX, PCX, and multiwalled carbon
      nanotubes. Under the optimized conditions, good linearity was obtained in the
      range of 0.05-6.0 MUg g(-1), with a correlation coefficient (r(2)) of ?0.9991.
      The recoveries at three spiking levels ranged from 90.1% to 113.5% with relative
      standard deviations (RSDs) of ?3.9%. The proposed M-G-PTE method was simple,
      economical, sensitive, and produced less organic pollution. Thus, it could be
      applied to the rapid screening of SAs in complicated bovine milk samples.

PMID- 24731338
TI  - High resolution melting (HRM) analysis of DNA--its role and potential in food
      analysis.
AB  - DNA based methods play an increasing role in food safety control and food
      adulteration detection. Recent papers show that high resolution melting (HRM)
      analysis is an interesting approach. It involves amplification of the target of
      interest in the presence of a saturation dye by the polymerase chain reaction
      (PCR) and subsequent melting of the amplicons by gradually increasing the
      temperature. Since the melting profile depends on the GC content, length,
      sequence and strand complementarity of the product, HRM analysis is highly
      suitable for the detection of single-base variants and small insertions or
      deletions. The review gives an introduction into HRM analysis, covers important
      aspects in the development of an HRM analysis method and describes how HRM data
      are analysed and interpreted. Then we discuss the potential of HRM analysis based
      methods in food analysis, i.e. for the identification of closely related species
      and cultivars and the identification of pathogenic microorganisms. 

PMID- 24731339
TI  - Retrogradation behaviour of high-amylose rice starch prepared by improved
      extrusion cooking technology.
AB  - Native rice starch (NRS, amylose/28.9%) was gelatinized by improved extrusion
      cooking technology (IECT) and retrograded (RRS) after low temperature storage (4 
      degrees C). The retrogradation behaviour of RRS was changed to low retrogradation
      percentage and low retrogradation rate. The retrogradation resulted in a high
      compact morphology. The melt enthalpy change and percentage of retrogradation of
      RRS was 3.68 J/g and 37.7%, respectively, compared to those of NRS (9.75 J/g,
      100%). The retrogradation percentage for RRS was low during storage as shown as a
      low retrogradation rate (0.21 d(-1)) and a high Avrami exponent (0.89). The
      pattern of rice starch changed from A-type to amorphous and B-type. Both the
      relative crystallinity of RRS (12.7%) by the X-ray diffractograms and the ratio
      of the band height (0.63) in the FTIR spectra were low. The analysis of
      retrogradation structure and short-range molecular order further confirmed the
      retrogradation behaviour of rice starch after IECT treatment.

PMID- 24731340
TI  - Antiradical and tea polyphenol-stabilizing ability of functional fermented
      soymilk-tea beverage.
AB  - This study examined the potential of two-step fermentation to preserve TPs in
      functional soy-tea beverage. Fermented soymilk-tea (FST) was produced by
      culturing Streptococcus thermophilus, Lactobacillus delbrueckii ssp. bulgaricus
      and Bifidobacterium longum in soymilk supplemented with tea extract (TE). Total
      phenolic content (TPC) and anti-radical activities were determined for FSTs and
      fermented soymilk (FS). A HPLC method was employed to quantify nine major tea
      phenolics in FST products. TPC was significantly higher (p<0.05) in FST than FS,
      in the order of green tea>oolong tea>black tea>soymilk. The FSTs were effective
      at scavenging DPPH-radical rather than hydroxyl radical. Optimal pH to stabilize
      TPs in SMT was ca. 5.7, which reduced total TP loss by ca. 40% compared with that
      obtained from products with TE supplemented at the beginning of fermentation. A
      gradual decrease in TPs was observed during storage (4  degrees C), with more
      than half of total TPs remained in FST after 8 weeks.

PMID- 24731341
TI  - Optimisation of a sample preparation method for the determination of fumonisin
      B(1) in rice.
AB  - A simple, rapid and cost-effective sample preparation method for the
      determination of fumonisin B1 in rice was optimised using a strategy of
      sequential experimental designs. Initially, a Plackett-Burman design was applied
      to select the statistically significant variables for the determination of
      fumonisin B1, and then, a central composite rotatable design was used to define
      the optimal conditions of these variables. The method involves extraction with a
      50% acetonitrile aqueous solution and glacial acetic acid, liquid-liquid
      partitioning with addition of anhydrous sodium sulphate and sodium chloride,
      followed by dispersive SPE clean-up with diatomaceous earth. The final extract
      was analysed by HPLC-FLD after precolumn derivatisation with ortho
      phthaldialdehyde. The optimised method was validated for selectivity, linearity,
      matrix effect, limits of detection and quantification, trueness, and precision,
      and then applied to commercial samples of polished rice. This is the first report
      of the occurrence of fumonisin B1 in commercial samples of polished rice from the
      Southeast region of Brazil. 

PMID- 24731342
TI  - A subzero 1H NMR relaxation investigation of water dynamics in tomato pericarp.
AB  - (1)H NMR relaxation times (T1 and T2) were measured at low field (0.47 T) in
      pericarp tissues of three tomato genotypes (Ferum, LA0147 and Levovil) at subzero
      temperature (-20  degrees C) and two ripening stages (mature green and red). The
      unfrozen water dynamics was characterised by two T1 and three T2 components. The
      relaxation time values and their associated relative populations allowed
      differentiating the ripening stage of only LA0147 and Levovil lines. But the
      three genotypes were unequivocally discriminated at the red ripe stage. The
      unfrozen water distribution was discussed in terms of specific interactions,
      especially with sugars, in relation with their osmoprotectant effects.

PMID- 24731343
TI  - Pectin modifications and the role of pectin-degrading enzymes during postharvest
      softening of Jonagold apples.
AB  - This study aimed at understanding softening in Jonagold apple (Malus*domestica
      Borkh.) fruits, by investigating pectin modifications and the evolution of pectin
      modifying enzymes during postharvest storage and ripening. Jonagold apples were
      harvested at commercial maturity and stored at different temperatures and
      controlled atmosphere conditions for 6 months, followed by exposure to ambient
      shelf life conditions (20  degrees C under air) for 2 weeks. The composition of
      the pectic material was analysed. Furthermore, the firmness and the ethylene
      production of the apples were assessed. Generally, the main changes in pectin
      composition associated with the loss of firmness during ripening in Jonagold
      apples were a loss of side chains neutral sugars, increased water solubility and
      decreased molar mass. Also, the activities of four important enzymes possibly
      involved in apple softening, beta-galactosidase, alpha-arabinofuranosidase,
      polygalacturonase and pectin methylesterase, were measured. Pectin-related enzyme
      activities highly correlated with ethylene production, but not always with pectin
      modifications.

PMID- 24731344
TI  - Solvent-free enzymatic synthesis of feruloylated structured lipids by the
      transesterification of ethyl ferulate with castor oil.
AB  - A novel enzymatic route of feruloylated structured lipids synthesis by the
      transesterification of ethyl ferulate (EF) with castor oil, in solvent-free
      system, was investigated. The transesterification reactions were catalysed by
      Novozym 435, Lipozyme RMIM, and Lipozyme TLIM, among which Novozym 435 showed the
      best catalysis performance. Effects of feruloyl donors, reaction variables, and
      ethanol removal on the transesterification were also studied. High EF conversion
      (~100%) was obtained under the following conditions: enzyme load 20% (w/w,
      relative to the weight of substrates), reaction temperature 90  degrees C,
      substrate molar ratio 1:1 (EF/castor oil), 72 h, vacuum pressure 10 mmHg, and 200
      rpm. Under these conditions, the transesterification product consisted of 62.6%
      lipophilic feruloylated structured lipids and 37.3% hydrophilic feruloylated
      lipids.

PMID- 24731345
TI  - Rapid detection of sildenafil analogue in Eurycoma longifolia products using a
      new two-tier procedure of the near infrared (NIR) spectra database.
AB  - A simple and cost-effective two-tier drug screening procedure comprises a
      'dedicated' NIR spectral database of common medicines and a 'unified' database
      was developed to detect the sildenafil analogue in Eurycoma longifolia products.
      Diffuse reflectance spectra of ten commercial herbal products containing E.
      longifolia were obtained over the wavelength range of 1100-2500 nm. The spectral
      search of two products purchased via the internet against a dedicated database of
      reputable E. longifolia products have resulted in the similarity index of more
      than 0.1 which indicated significantly different spectra. Further searches
      against the unified database showed a close match to the spectra of drug
      containing sildenafil citrate suggesting the presence of a sildenafil analogue.
      This finding was supported by clustering of these spectra in the PCA score plot
      within 5% significance level. This approach has alleviated the use of reference
      product or standard active for direct comparison and has a potential to be used
      for adulterated food and drugs detection.

PMID- 24731346
TI  - Sol-gel hybrid methyltrimethoxysilane-tetraethoxysilane as a new dispersive solid
      phase extraction material for acrylamide determination in food with direct gas
      chromatography-mass spectrometry analysis.
AB  - A sol-gel hybrid sorbent, methyltrimethoxysilane-tetraethoxysilane (MTMOS-TEOS)
      was successfully used as new dispersive solid phase extraction (dSPE) sorbent
      material in the determination of acrylamide in several Sudanese foods and
      analysis using GC-MS. Several important dSPE parameters were optimised. Under the
      optimised conditions, excellent linearity (r(2)>0.9998) was achieved using matrix
      matched standard calibration in the concentration range 50-1000 MUg kg(-1). The
      limits of detection (LOD) and limit of quantification ranged from 9.1 to 12.8
      MUg/kg and 27.8-38.9 MUg/kg, respectively. The precision (RSD%) of the method was
      ?6.6% and recoveries of acrylamide obtained were in the range of 88-103%, (n=3).
      The LOD obtained is comparable with the LODs of primary secondary amine dSPE. The
      proposed MTMOS-TEOS dSPE method is direct and safe for acrylamide analysis,
      showed reliable method validation performances and good cleanup effects. It was
      successfully applied to the analysis of acrylamide in real food samples.

PMID- 24731347
TI  - Development of ultrasensitive direct chemiluminescent enzyme immunoassay for
      determination of aflatoxin M1 in milk.
AB  - A direct competitive chemiluminescent enzyme-linked immunosorbent assay (CL
      ELISA) for detecting aflatoxin M1 (AFM1) was developed. To improve the
      sensitivity of the assay, a mixture of 3-(10'-phenothiazinyl)-propane-1-sulfonate
      (SPTZ) and 4-morpholinopyridine (MORPH) was used to enhance peroxidase-induced
      CL. The concentrations of the coating anti-AFM1 antibody and the conjugate of
      AFB1 with horseradish peroxidase the conditions of the chemiluminescent assay
      were varied to optimise the condition of the chemiluminescent assay. The lower
      detection limit values and dynamic working range of CL-ELISA of AFM1 were 0.001
      ng mL(-1) and 0.002-0.0075 ng mL(-1), respectively. A 20-fold dilution of milk
      samples prevented a matrix effect of the milk and allowed measurement of AFM1 at
      concentrations below than the maximum acceptable limit. Values of recovery within
      and between assays were 81.5-117.6% and 86-110.6%, respectively. The results of
      using the developed CL-ELISA to analyse samples of six brands of milk that were
      purchased in Taiwan revealed that AFM1 was absent from all studied samples.

PMID- 24731348
TI  - Optimization conditions of samples saponification for tocopherol analysis.
AB  - A full factorial design 2(2) (two factors at two levels) with duplicates was
      performed to investigate the influence of the factors agitation time (2 and 4 h)
      and the percentage of KOH (60% and 80% w/v) in the saponification of samples for
      the determination of alpha, beta and gamma+delta-tocopherols. The study used
      samples of peanuts (cultivar armadillo), produced and marketed in Maringa, PR.
      The factors % KOH and agitation time were significant, and an increase in their
      values contributed negatively to the responses. The interaction effect was not
      significant for the response delta-tocopherol, and the contribution of this
      effect to the other responses was positive, but less than 10%. The ANOVA and
      response surfaces analysis showed that the most efficient saponification
      procedure was obtained using a 60% (w/v) solution of KOH and with an agitation
      time of 2 h.

PMID- 24731349
TI  - Oleuropein as a bioactive constituent added in milk and yogurt.
AB  - Oleuropein is a bioactive natural product from olives known to display a broad
      variety of health beneficial properties. However its presence in most edible
      olives is lowered due to debittering. In this respect, we envisaged the
      incorporation of oleuropein into dairy products (cow's milk and yogurt) aiming to
      produce novel functional foods. Additionally, an analytical method for the
      monitoring of oleuropein in milk and yogurt was also developed and validated.
      Oleuropein was not affected during heat treatment of milk, while during the milk
      fermentation process it was not hydrolysed by the produced acids. Oleuropein was
      not metabolised by lactic acid bacteria, did not inhibit their growth and its
      stability in the final products was proven. The novel products displayed same
      taste, colour and texture as the conventional ones. Results herein indicate that
      oleuropein can be added as an active ingredient in milk and yogurt preparations
      to provide two novel functional dairy products. 

PMID- 24731350
TI  - Appraisal of antioxidant, anti-hemolytic and DNA shielding potentialities of
      chitosaccharides produced innovatively from shrimp shell by sequential treatment
      with immobilized enzymes.
AB  - Chitosaccharides (CS) of varied size were prepared from shrimp shell through
      sequential catalysis, using crude protease and chitinase enzymes immobilized on
      agar beads. In the optimized state, immobilization yield and activity yield for
      protease were 84% and 62%, and for chitinase were 75% and 57%, respectively.
      Immobilized protease and chitinase treatment improved CS yields (101 MUg/ml) and
      retained 63% and 52% of activities after 10 reuses, respectively. Stronger
      radical-scavenging activity (RSA) of CS against ABTS, DPPH and hydroxyl radical
      was noted with EC50 values 19.1, 26.4 and 29.6 MUg/ml, respectively. Peroxyl and
      superoxide RSAs of 96.8% and 88.6% were noticed at 70 MUg/ml of CS. Singlet
      oxygen quenching, reducing power and ferrous ion-chelating activities of CS were
      also pronounced. CS reasonably reduced oxidative damage of DNA, protein and RBC
      by inhibiting H2O2 and AAPH radicals. Reversible CS-DNA condensation leads to DNA
      stabilization without changing its conformation and advocates its employment in
      gene therapy.

PMID- 24731351
TI  - Simple assay of trehalose in industrial yeast.
AB  - Trehalose is an essential chemical marker to control a quality of the industrial
      yeast strains and to assess a tolerance of the yeasts products to different
      physical stresses. A high-performance liquid chromatography analysis with charged
      aerosol detection (HPLC-CAD) was developed for trehalose determination in
      industrial yeasts. The method offers a linearity in the range of 5.0-15 mM with
      linear regression coefficient R(2)=0.9995, a good reproducibility and relatively
      short analysis time (7 min). Trehalose can be detected at concentrations as low
      as 0.07 mM, and limit of precise quantification is 0.2 mM. The coefficient of
      variation (CV%) is 0.3%. The developed method is more sensitive compared with
      conventional chromatography procedure with UV absorbance detection. It was shown
      that the proposed method can be used in baker's industry to control a quality of
      the yeast products and to assess biotechnological significance of the yeast
      strains.

PMID- 24731352
TI  - ZnCl2-mediated practical protocol for the synthesis of Amadori ketoses.
AB  - An efficient and practical protocol for the synthesis of Amadori ketoses N-(1
      deoxy-D-fructose-1-yl) amino acid (amino acid=L-valine (1), L-leucine (2), L
      isoleucine (3), L-tryptophan (4), L-phenylalanine (5), L-arginine (6) has been
      accomplished by employing ZnCl2 as a catalyst. The developed method circumvents
      protection and deprotection steps as well as tedious ion-exchange and column
      chromatographic techniques. The accomplished Amadori ketoses showed moderate to
      weak angiotensin I converting enzyme (ACE) inhibitory activity.

PMID- 24731353
TI  - Fast and solvent-free quantitation of boar taint odorants in pig fat by stable
      isotope dilution analysis-dynamic headspace-thermal desorption-gas
      chromatography/time-of-flight mass spectrometry.
AB  - Boar taint is a specific off-odour of boar meat products, known to be caused by
      at least three unpleasant odorants, with very low odour thresholds. Androstenone
      is a boar pheromone produced in the testes, whereas skatole and indole originate
      from the microbial breakdown of tryptophan in the intestinal tract. A new
      procedure, applying stable isotope dilution analysis (SIDA) and dynamic headspace
      thermal desorption-gas chromatography/time-of-flight mass spectrometry (dynHS-TD
      GC/TOFMS) for the simultaneous quantitation of these boar taint compounds in pig
      fat was elaborated and validated in this paper. The new method is characterised
      by a simple and solvent-free dynamic headspace sampling. The deuterated compounds
      d3-androstenone, d3-skatole and d6-indole were used as internal standards to
      eliminate matrix effects. The method validation performed revealed low limits of
      detection (LOD) and quantitation (LOQ) with high accuracy and precision, thus
      confirming the feasibility of the new dynHS-TD-GC/TOFMS approach for routine
      analysis. 

PMID- 24731354
TI  - The characterization of caffeine and nine individual catechins in the leaves of
      green tea (Camellia sinensis L.) by near-infrared reflectance spectroscopy.
AB  - Near-infrared reflectance spectroscopy (NIRS) was used to determine the contents
      of caffeine and nine individual catechins in tea leaves. A total of 665 samples
      were scanned by NIRS, and also by high performance liquid chromatography coupled
      to a diode array detector to determine the contents of caffeine and nine
      individual catechins. The calibration models for caffeine, EGC, C, EGCG, EC, ECG,
      and total catechins had high r(2) (more than 0.90) and RSP (the ratio of standard
      deviation of reference data to SEP(C) in the external validation set) values
      (more than 4.1), indicating a good correlation between reference values and NIRS
      predicted values. In contrast, the calibration models of GC and EGCG-3Me had low
      r(2) and RSP values (below 0.8 and 2.0). Therefore, these results suggest that
      NIRS could be applied for the rapid determination of the contents of caffeine,
      EGC, C, EGCG, EC, ECG, and total catechins in tea leaves for breeding programs
      that develop high-quality tea plants. 

PMID- 24731355
TI  - Optimisation of the microencapsulation of tuna oil in gelatin-sodium
      hexametaphosphate using complex coacervation.
AB  - The microencapsulation of tuna oil in gelatin-sodium hexametaphosphate (SHMP)
      using complex coacervation was optimised for the stabilisation of omega-3 oils,
      for use as a functional food ingredient. Firstly, oil stability was optimised by
      comparing the accelerated stability of tuna oil in the presence of various
      commercial antioxidants, using a RancimatTM. Then zeta-potential (mV), turbidity
      and coacervate yield (%) were measured and optimised for complex coacervation.
      The highest yield of complex coacervate was obtained at pH 4.7 and at a gelatin
      to SHMP ratio of 15:1. Multi-core microcapsules were formed when the mixed
      microencapsulation system was cooled to 5  degrees C at a rate of 12  degrees
      C/h. Crosslinking with transglutaminase followed by freeze drying resulted in a
      dried powder with an encapsulation efficiency of 99.82% and a payload of 52.56%.
      Some 98.56% of the oil was successfully microencapsulated and accelerated
      stability using a RancimatTM showed stability more than double that of non
      encapsulated oil.

PMID- 24731356
TI  - A novel core-shell magnetic nano-sorbent with surface molecularly imprinted
      polymer coating for the selective solid phase extraction of dimetridazole.
AB  - A novel core-shell magnetic nano-sorbent with surface molecularly-imprinted
      polymer coating was prepared via a sol-gel process. Methyltrimethoxysilane and 3
      aminopropyltriethoxysilane were used as functional monomers, tetraethyl
      orthosilicate as cross-linker, and Al(3+) as dopant to generate Lewis acid sites
      in the silica matrix for the metal coordinate interactions with the template
      dimetridazole (DMZ). The ratios of the monomers, the dopant, and the cross
      linker, were optimised by a OA9 (3(4)) orthogonal array design. The resultant
      sorbent was characterised by scanning electron microscopy, transmission electron
      microscopy, Fourier transform infrared spectroscopy, powder X-ray diffraction,
      and magnetometry. The binding performances of the sorbent were evaluated by
      static, kinetic and selective adsorption experiments. The nano-sorbent was
      successfully applied to solid phase extraction followed by spectrophotometric
      determination of DMZ in real samples. Spiked recoveries ranged from 90.33% to
      106.20% for egg, milk powder, and pig feed samples, with relative standard
      deviations of less than 4.54%. 

PMID- 24731357
TI  - Development of a method to recovery and amplification DNA by real-time PCR from
      commercial vegetable oils.
AB  - This study describes the design of a suitable DNA isolation method from
      commercial vegetable oils for the application of DNA markers for food safety and
      traceability. Firstly, a comparative study was made of eight methods for the
      recovery of high quality DNA from olive, sunflower and palm oils, and a CTAB
      based method was selected. In order to optimize this method, the effect of the
      organic compounds and several components in the lysis buffer and the lysis and
      precipitation time were evaluated. For the purpose of overcoming the limitations
      detected in spectrophotometric and PCR DNA yield evaluations, the performance of
      the extraction protocols during the optimization processes was evaluated using
      qPCR. The suggested DNA extraction optimized is less time consuming than other
      conventional DNA extraction methods, uses a reduced oil volume and is cheaper
      than available commercial kits. Additionally, the applicability of this method
      has been successfully assayed in ten commercial vegetable oils and derivatives. 

PMID- 24731358
TI  - An alternative method for protein determination without melamine interference.

PMID- 24731359
TI  - Structural elucidation and cellular antioxidant activity evaluation of major
      antioxidant phenolics in lychee pulp.
AB  - Lychee pulp contains phenolic compounds that are strong antioxidants, but the
      identities of the major antioxidants present are unknown. In the present study,
      the major contributors to the antioxidant activity of fresh lychee pulp were
      identified and their cellular antioxidant activities were investigated. Aqueous
      acetone extracts of lychee pulp were fractionated on polyamide resin, and those
      fractions with the largest antioxidant and radical scavenging activities were
      selected using cellular antioxidant activity and oxygen radical absorbance
      capacity assays. Three compounds that were major contributors to the antioxidant
      activity in these fractions were obtained by reverse-phase preparative HPLC and
      identified as quercetin 3-O-rutinoside-7-O-alpha-L-rhamnosidase (quercetin 3-rut
      7-rha), quercetin 3-O-rutinoside (rutin) and (-)-epicatechin using NMR
      spectroscopy, HMBC, and ESI-MS spectrometry. The concentration of quercetin 3-rut
      7-rha was 17.25mg per 100g of lychee pulp fresh weight. This is the first report
      of the identification and cellular antioxidant activity of quercetin 3-rut-7-rha
      from lychee pulp.

PMID- 24731360
TI  - Comparison of extraction methods for the identification and quantification of
      polyphenols in virgin olive oil by ultra-HPLC-QToF mass spectrometry.
AB  - In this work, liquid-liquid extraction (LLE) and solid phase extraction (SPE), of
      polyphenols from a VOO sample were optimised by a Plackett-Burman experimental
      design; then the two extraction techniques capabilities were compared. By using
      HPLC-DAD, the extraction ability of SPE with the diol phase and LLE were similar.
      The two methods were further evaluated with ultra HPLC-ESI QToF in negative ion
      mode by recoveries of standards and matched comparison of the peak area of 40
      identified and 27 unidentified compounds. Conclusions indicate that LLE gives
      better recoveries for highly polar, non-polar, and some polyphenols suspected to
      contain a nitrogen atom, while for the others the two methods seem to be equally
      suitable. The presence of nitrogen-containing polyphenols was confirmed in
      positive ionisation mode in LLE extract, whereas in the SPE extract they were not
      present. One of them was tentatively identified as a compound containing tyrosine
      and methyl-decarboxymetyl-eleanoic acid moieties. 

PMID- 24731361
TI  - Enantiomeric purity determination of (L)-amino acids with pre-column
      derivatization and chiral stationary phase: development and validation of the
      method.
AB  - A simple, efficient and general HPLC method for the determination of enantiomeric
      purity of a series of (L)-amino acids was developed. In order to improve the
      detection sensitivity, pre-column derivatization was adopted and 7-chloro-4
      nitrobenzoxadiazole (NBD-Cl) was selected as derivatization reagent. NBD-amino
      acid enantiomers were then enantioseparated on a Pirkle-type chiral stationary
      phase, Sumichiral OA-2500S (250 mm * 4.6 mm, 5 MUm), using a mobile phase
      composed of acetonitrile-methanol (50:50, v/v) containing 5 mmol L(-1) citric
      acid at the flow rate of 0.5 mL min(-1). The detection wavelength was 470 nm. All
      the eleven pairs of tested amino acid enantiomers were well separated, and trace
      amounts of (D)-amino acids (0.5%) in the presence of a large excess of
      corresponding (L)-enantiomers could be quantified. The proposed method was
      validated in terms of selectivity, precision, linearity range, LOD, LOQ and
      accuracy, and then successfully applied to the determination of enantiomeric
      purity in bulk samples of (L)-amino acids.

PMID- 24731362
TI  - Interaction of flavan-3-ol derivatives and different caseins is determined by
      more than proline content and number of proline repeats.
AB  - Interactions of Type A and B flavan-3-ol dimers (procyanidins) and several
      monomeric flavan-3-ols, with alpha-casein and beta-casein, were investigated.
      Binding affinities measured were related to the ligands structure, including
      several properties (e.g. intrinsic flexibility (number of rotatable bonds) and
      hydrophobicity), and to the amino-acid composition of the caseins. A monomeric
      flavan-3-ol esterified with gallic acid (EGCG) had a five to ten times higher
      affinity to caseins compared to the non-galloylated dimeric flavan-3-ols. In this
      case, the larger number of rotatable bonds in EGCG might be accountable for this
      difference. Comparing flavan-3-ol dimers, intrinsic flexibility did not
      consistently promote interactions, as procyanidin A1 displayed a higher affinity
      to alpha-casein than the supposedly more flexible B-type dimers investigated.
      Despite its higher content of proline, compared to alpha-casein, beta-casein did
      not always have a higher affinity for the ligands investigated (e.g. no
      interaction with procyanidin A1 detected). These results suggest that more
      factors than proline content and the number of proline repeats govern phenolic
      casein interactions.

PMID- 24731363
TI  - Mild method for removal of cyanogens from cassava leaves with retention of
      vitamins and protein.
AB  - A mild method was developed to remove cyanogens from cassava leaves that involved
      three consecutive steps (1) pounding, (2) standing for 2h in the sun or 5h in the
      shade in the tropics and (3) washing three times in water. Four cassava cultivars
      were used and the mean residual total cyanide content after steps 1, 2 and 3 was
      28%, 12% and 1%, respectively. The pounded cassava leaves retained their bright
      green colour and texture. The traditional method for removing cyanogens from
      pounded cassava leaves is by boiling in water which removed all cyanogens in 10
      min. However this method caused the pounded leaves to become dull green in colour
      and would cause considerable losses of vitamins, protein and methionine, which
      are already in short supply in the diet of poor village people in tropical
      Africa.

PMID- 24731364
TI  - Preparation, evaluation and application of diazinon imprinted polymers as the
      sorbent in molecularly imprinted solid-phase extraction and liquid chromatography
      analysis in cucumber and aqueous samples.
AB  - A series of diazinon imprinted polymers (MIPs) were prepared and evaluated in the
      binding study in comparison with a non-imprinted polymer (NIP). The optimised MIP
      was evaluated as a sorbent, for extraction and preconcentration of diazinon from
      aqueous media and cucumber tissue. The HPLC-UV method was calibrated, in the
      range of 0.025-10 mg/kg. The results indicated that the optimised MIP had an
      excellent affinity for diazinon. The molecularly imprinted solid-phase extraction
      (MISPE) procedure was optimised with a recovery of 77-98%, in aqueous solution,
      and a recovery of 82-110%, in cucumber. The intra-day variation and inter-day
      variation values were less than 8.26% and 9.7%, respectively. Our data showed
      that, the MIP enabled the extraction of trace amounts of diazinon successfully
      from aqueous solution and cucumber, demonstrating the potential of MISPE for
      rapid, sensitive and cost-effective sample analysis.

PMID- 24731365
TI  - Effects of soybean oligosaccharides on antioxidant enzyme activities and insulin
      resistance in pregnant women with gestational diabetes mellitus.
AB  - The effects of soybean oligosaccharides (SBOS) on antioxidant enzyme activities
      and insulin resistance in pregnant women with gestational diabetes mellitus (GDM)
      were investigated. Ninety-seven pregnant women with GDM were randomly divided
      into two groups, the control group (51 cases) and the SBOS group (46 cases).
      Before the group separation, the blood sugar level in patients was maintained
      stable by regular diet and insulin treatment. The control group was continued
      with the insulin treatment, while the SBOS group was treated with the combination
      of insulin and SBOS. Results showed that SBOS were able to reduce oxidative
      stress and alleviate insulin resistance in pregnant women with GDM, which
      indicates that SBOS may play an important role in the control of GDM
      complications. 

PMID- 24731366
TI  - Preparative isolation and purification of phlorotannins from Ecklonia cava using
      centrifugal partition chromatography by one-step.
AB  - Various bioactive phlorotannins of Ecklonia cava (e.g., dieckol, eckol, 6,6
      bieckol, phloroglucinol, phloroeckol, and phlorofucofuroeckol-A) are reported.
      However, their isolation and purification are not easy. Centrifugal partition
      chromatography (CPC) can be used to efficiently purify the various bioactive
      compounds efficiently from E. cava. Phlorotannins are successfully isolated from
      the ethyl acetate (EtOAc) fraction of E. cava by CPC with a two-phase solvent
      system comprising n-hexane:EtOAc:methanol:water (2:7:3:7, v/v) solution. The
      dieckol (fraction I, 40.2mg), phlorofucofuroeckol-A (fraction III, 31.1mg), and
      fraction II (34.1mg) with 2,7-phloroglucinol-6,6-bieckol and pyrogallol
      phloroglucinol-6,6-bieckol are isolated from the crude extract (500 mg) by a one
      step CPC system. The purities of the isolated dieckol and phlorofucofuroeckol-A
      are ?90% according to high performance liquid chromatography (HPLC) and
      electrospray ionization multi stage tandem mass spectrometry analyses. The
      purified 2,7-phloroglucinol-6,6-bieckol and pyrogallol-phloroglucinol-6,6-bieckol
      are collected from fraction II by recycle-HPLC. Thus, the CPC system is useful
      for easy and simple isolation of phlorotannins from E. cava.

PMID- 24731367
TI  - Changes in fatty acid composition and lipid profile during koji fermentation and
      their relationships with soy sauce flavour.
AB  - Evolution of lipids during koji fermentation and the effect of lipase
      supplementation on the sensory properties of soy sauce were investigated. Results
      showed that total lipids of the koji samples were in the range of 16-21%. The
      extracted lipid of initial koji consisted mainly of triacylglycerols (TAGs,
      >98%), followed by phospholipids (PLs), diglycerides (DAGs), monoacylglycerols
      (MAGs) and free fatty acids (FFAs). As the fermentation proceeded, peroxide value
      of the lipids decreased while carbonyl value increased (p<0.05). Linoleic acid
      was utilised fastest according to the fatty acid composition of total lipids, and
      preferential degradation of PLs to liberate FFAs was also observed. Moreover,
      phospholipase supplementation had significant influence on the sensory
      characteristics of soy sauce, especially enhanced (p<0.05) scores for the umami
      and kokumi taste attributes. All these results indicated that the control of PLs
      utilisation during fermentation was a potential method to improve soy sauce's
      characteristic taste.

PMID- 24731368
TI  - A rapid immunomagnetic beads-based immunoassay for the detection of beta-casein
      in bovine milk.
AB  - An immunomagnetic beads-based enzyme-linked immunosorbent assay (IMBs-ELISA) was
      developed for the detection of beta-casein in bovine milk. Immunomagnetic beads
      (IMBs) were employed as the solid phase. The anti-beta-casein monoclonal antibody
      (McAb) bound to IMBs was used as capture probe and an anti-beta-casein polyclonal
      antibody (PcAb), labelled with horseradish peroxidase (HRP), was employed as
      detector probe. Three reaction and two washing steps were needed. Each reaction
      needed 10 min or less, which significantly shortened detection compared with
      classic sandwich ELISA. beta-Casein in bovine milk was detected across a linear
      range (2-128 MUg mL(-1)). Application results were in accordance with the
      Kjejdahl method, which suggests the IMBs-ELISA is rapid and reliable for the
      detection of beta-casein in bovine milk.

PMID- 24731369
TI  - Identification, content and distribution of anthocyanins and low molecular weight
      anthocyanin-derived pigments in Spanish commercial red wines.
AB  - The content and distribution of low molecular weight red wine pigments
      (anthocyanins, flavanol-anthocyanins adducts and pyranoanthocyanins) has been
      analysed in 283 wine samples. A total of 90 red wine pigments were identified and
      up to 68 of them quantified in most of the wine samples. The content of the
      different pigments classes accounted for wide ranges of values, because of the
      diversity of the commercial wines regarding grape cultivar and age. Garnacha
      young wines were prone to contain higher hydroxyphenyl-pyranoanthocyanin
      concentrations. The aging had an effect of making uniform the concentrations and
      molar percentages of every type of pigments, and only slight differences among
      wine groups were found for B-type vitisins (highest values for Syrah wines) and
      10-hydroxyphenyl-pyranoanthocyanins (highest values for Merlot wines). Among
      Tempranillo wines, the ethylidene-bridged flavanol-anthocyanin adducts were the
      most affected by disappearance during aging, whereas hydroxyphenyl
      pyranoanthocyanins increased their contribution in most of those aged wines. 

PMID- 24731370
TI  - Dispersive solid-phase extraction followed by high-performance liquid
      chromatography/tandem mass spectrometry for the determination of ricinine in
      cooking oil.
AB  - A rapid and accurate method by liquid chromatography/tandem mass spectrometry (LC
      MS/MS) using positive electrospray was established for the determination of
      ricinine in cooking oils. The homogenized samples, spiked with (13)C6-labelled
      ricinine as an internal standard, were extracted using ethanol/water (20:80, v/v)
      and purified by dispersive solid-phase extraction (dSPE) using primary-secondary
      amine (PSA) and C18 as adsorbents. The extract was separated in a short C18
      reversed-phase column using methanol/water (25:75, v/v) as the mobile phase and
      detected in multiple reaction monitoring (MRM) mode with the absolute matrix
      effect of 93.2-102.2%. The alkali-metal adduct ions were discussed and the
      mass/mass fragmentation pathway was explained. Ricinine showed good linearity in
      the range of 0.5-50.0 MUg/kg with the limit of quantitation 0.5 MUg/kg. The
      recoveries were between 86.0% and 98.3% with the intra- and inter-day RSDs of 2.6
      7.0%, 5.5-10.8%, respectively. This method could be applied to the rapid
      quantification of ricinine in cooking oils.

PMID- 24731371
TI  - Tangeretin-loaded protein nanoparticles fabricated from zein/beta-lactoglobulin:
      preparation, characterization, and functional performance.
AB  - The aim of this study was to design a colloidal delivery system to encapsulate
      poor water-soluble bioactive flavonoid tangeretin so that it could be utilized in
      various food products as functional ingredient. Tangeretin-loaded protein
      nanoparticles were produced by mixing an organic phase containing zein and
      tangeretin with an aqueous phase containing beta-lactoglobulin and then converted
      into powder by freeze-drying. This powder formed a colloidal suspension when
      dispersed in water that is relatively stable to particle aggregation and
      sedimentation. The influence of temperature, ionic strength, and pH on the
      stability of the protein nanoparticles was tested. Extensive particle aggregation
      occurred at high ionic strength (>100mM) and intermediate pH (4.5-5.5) due to
      reduced electrostatic repulsion. Extensive aggregation also occurred at
      temperatures exceeding 60  degrees C, which was presumably due to increased
      hydrophobic attraction. Overall, this study shows that protein-based
      nanoparticles can be used to encapsulate bioactive tangeretin so that it can be
      readily dispersed in compatible food products.

PMID- 24731372
TI  - Determination of nonylphenol ethoxylate and octylphenol ethoxylate surfactants in
      beehive samples by high performance liquid chromatography coupled to mass
      spectrometry.
AB  - Nonylphenol and octylphenol ethoxylates (NP(EO)n and OP(EO)n) are major toxicants
      in agrochemicals used around beehives. Here we developed a LC-MS method for
      analysis of NP(EO)3-13 and OP(EO)3-13 oligomers in bee hive matrices. Less than 2
      g of honey, pollen or wax were extracted using the QuEChERS (Quick, Easy, Cheap,
      Effective, Rugged and Safe) approach. Recoveries for each oligomer in all
      matrices are between 75% and 111% at three spiked concentrations. The method
      proved to be rapid, precise and sensitive. Five honey, 10 pollen and 12 wax
      samples were collected and analysed. NP(EO)n was detected in every sample with
      concentrations ranging from 26 ppb to 10,239 ppb. Much higher NP(EO)n residues
      levels were found in wax followed by pollen than in honey. OP(EO)n concentrations
      on average were more than 10 times lower in pollen and wax. This method
      demonstrates a probable wide occurrence of alkylphenol ethoxylates in USA
      beehives.

PMID- 24731373
TI  - Production and characterisation of potato patatin-galactose,
      galactooligosaccharides, and galactan conjugates of great potential as functional
      ingredients.
AB  - Potato proteins are of high interest because of their high nutritional quality
      and multiple health benefits, but they are currently undervalued due to their
      limited solubility and stability. Glycated patatin (PTT) with galactose,
      galactooligosaccharides (GOSs) and galactan were produced through the Maillard
      reaction and characterised structurally and functionally. Fourier-transform
      infrared and fluorescence spectroscopy data revealed important changes in total
      secondary structures through glycation with GOSs (61.2%) and galactan (36.7%) and
      also significant tertiary structural changes leading to an exposure of tryptophan
      residues. These structural changes led to more heat stable forms of PTT with a
      higher unfolding temperature (70-90  degrees C) than the unmodified protein (50
      70  degrees C) and with higher antioxidant activity. PTT:galactose conjugates
      exhibited similar thermal stability and pH-structural behaviour to native PTT.
      However, the high level of galactose conjugation to PTT and increased exposure of
      hydrophobic residues led to a significant increase in its emulsifying stability
      at pH 3.

PMID- 24731374
TI  - A novel method for predicting antioxidant activity based on amino acid structure.
AB  - Epidemiological studies show a positive correlation between oxidative stress and
      chronic disease development such as heart disease and cancer. While several
      antioxidant compounds with varying physical and chemical characteristics are able
      to reduce oxidative stress in biological systems, relatively few studies have
      been performed to examine the structural characteristics that produce potent
      antioxidants. We examined 20 essential and non-essential amino acids using the
      ORAC assay and used a simplest-case amino acid model to gather data to make
      predictions regarding the antioxidant activity of non-amino acid compounds; we
      also tested our findings on chalcone and nitrone data from the current
      literature. We observed that the sp(2)-hybridized carbons were the most
      consistent predictors of antioxidant activity in all groups. Valence electron to
      carbon ratio and length of conjugated double bond groups also emerged as
      important structural characteristics. Further testing may help to elucidate more
      accurate trends, as well as nonlinear relationships. 

PMID- 24731375
TI  - The determination of botanical origin of honeys based on enantiomer distribution
      of chiral volatile organic compounds.
AB  - The enantiomer ratios of chiral volatile organic compounds in rapeseed, chestnut,
      orange, acacia, sunflower and linden honeys were determined by multi-dimensional
      gas chromatography using solid phase microextraction (SPME) as a sample pre
      treatment procedure. Linalool oxides, linalool and hotrienol were present at the
      highest concentration levels, while significantly lower amounts of alpha
      terpineol, 4-terpineol and all isomers of lilac aldehydes were found in all
      studied samples. On the other hand, enantiomer distribution of some chiral
      organic compounds in honey depends on their botanical origin. The significant
      differences in enantiomer ratio of linalool were observed for rapeseed honey that
      allows us to distinguish this type of honey from the other ones. The enantiomer
      ratios of lilac aldehydes were useful for distinguishing of orange and acacia
      honey from other studied monofloral honeys. Similarly, different enantiomer ratio
      of 4-terpineol was found for sunflower honeys. 

PMID- 24731376
TI  - Low molecular-weight phenols in Tannat wines made by alternative winemaking
      procedures.
AB  - Low molecular weight phenols of Tannat red wines produced by Traditional
      Maceration (TM), Prefermentative Cold Maceration (PCM), Maceration Enzyme (ENZ)
      and grape-Seed Tannins additions (ST), were performed and discussed. Alternatives
      to TM increased wine phenolic contents but unequally, ST increased mainly smaller
      flavans-3-ol, PCM anthocyanins and ENZ proanthocyanidins (up to 2250 mg/L).
      However low molecular weight flavan-3-ols remained below 9 mg/L in all wines,
      showing that there is not necessarily a correspondence between wine richness in
      total tannins and flavan-3-ols contents at low molecular weight. PCM wines had
      particularly high concentrations of tyrosol and tryptophol, yeast metabolism
      derived compounds. The use of grape-seed enological tannins did not increase
      grape seed derived phenolic compounds such as gallic acid. Caftaric acid was
      found in concentrations much higher than those reported in other grape varieties.
      Wine phenolic content and composition was considerably affected by the winemaking
      procedures tested.

PMID- 24731377
TI  - Phytochemicals in date co-products and their antioxidant activity.
AB  - The date agro-industry needs to find appropriate techniques to give value to
      their co-products. This study analyzes twelve intermediate food products (IFPs)
      from date co-products, Medjool and Confitera cv. at several ripening stages,
      blanched and unblanched, for their content in bioactive compounds (phenols,
      tannins, flavonoids, carotenoids and anthocyanins) and the antioxidant activity
      (AA). IFPs from the more unripe stages had the highest AA and phytochemicals
      content, mainly phenols, up to 1.4 g GAE/100 g, with high proportions of tannins.
      Flavonoids were found in high amounts, up to 874 mg RE/100 g. Among the AA are
      significant the antiradical efficiency (4.62 mM TE/100 g) and chelating activity
      (252 MUM EDTA/100 g). Blanching was beneficial for Confitera IFPs. A positive
      correlation was found between phenols, tannins and flavonoids and the AA; and
      their content could be used as indicator of the AA. Date IFPs have potential use
      as an antioxidant functional ingredient.

PMID- 24731378
TI  - Quantitative determination of carmine in foods by high-performance liquid
      chromatography.
AB  - A simple and rapid method has been developed and validated for the determination
      of carmine in foods. Samples were homogenised and extracted with 0.05 M NaOH,
      followed by centrifugation. The resulting solution was filtered and injected to
      HPLC. Carmine was separated by HPLC using an NovaPak C18 column coupled to a
      photodiode array detector. The contents of carmine were finally quantified using
      corresponding calibration curves over ranges of 1.0-100 MUg ml(-1), with good
      correlation coefficients (r(2)=0.9999). The recoveries of carmine from foods
      spiked at levels of 10, 50, and 100 MUg g(-1) which ranged from 90.4% to 96.2%
      with relative standard deviations between 2.8% and 6.8%. Limit of detection and
      limit of quantification of carmine were 0.4 and 1.0 MUg ml(-1), respectively.
      This method was found to be useful to distinguish carmine from carminic acid, a
      major component of cochineal extract. The method has been successfully applied to
      various foods.

PMID- 24731379
TI  - The effect of different alcoholic beverages on blood alcohol levels, plasma
      insulin and plasma glucose in humans.
AB  - In the present work we studied the effects of four alcoholic beverages on blood
      alcohol levels, plasma insulin concentrations and plasma glucose concentrations
      in men and women. The volunteers were healthy non-smokers and they were divided
      according to sex into two groups of ten individuals. The alcoholic beverages used
      in the study were beer, red wine, whisky and "cachaca". In men, ingestion of the
      distilled drinks promoted a spike in blood alcohol levels more quickly than
      ingestion of the fermented drinks. In women, beer promoted the lowest blood
      alcohol levels over the 6h of the experiment. Whisky promoted highest blood
      alcohol levels in both sexes. The ingestion of wine promoted a significant
      difference in relation to the blood alcohol concentration (BAC) as a function of
      gender. The ingestion of cachaca by women produced BAC levels significantly
      smaller than those obtained for wine. 

PMID- 24731380
TI  - Improvements in the malaxation process to enhance the aroma quality of extra
      virgin olive oils.
AB  - The influence of olive paste preparation conditions on the standard quality
      parameters, as well as volatile profiles of extra virgin olive oils (EVOOs) from
      Morisca and Manzanilla de Sevilla cultivars produced in an emerging olive growing
      area in north-western Spain and processed in an oil mill plant were investigated.
      For this purpose, two malaxation temperatures (20/30  degrees C), and two
      malaxation times (30/90 min) selected in accordance with the customs of the area
      producers were tested. The volatile profile of the oils underwent a substantial
      change in terms of odorant series when different malaxation parameters were
      applied.

PMID- 24731381
TI  - Rutin and quercetin enhance glucose uptake in L6 myotubes under oxidative stress
      induced by tertiary butyl hydrogen peroxide.
AB  - Scientific evidence suggests a strong link between the oxidative stress-induced
      pathways and onset of diabetes and its complications. The present study evaluates
      the antidiabetic potential of the flavonoids, rutin and its metabolite quercetin
      under oxidative stress induced by tertiary butyl hydrogen peroxide (TBHP). Our
      results demonstrate that reactive oxygen species generated by TBHP decreased
      markedly in the L6 cells on preincubation with flavonoids in a dose-dependent
      manner and remarkably retrieved the glutathione level which was drastically
      decreased on oxidative challenge. These flavonoids were also found to prevent
      lipid peroxidation in L6 myoblast. Flavonoids increased glucose following chronic
      and acute pretreatment in the presence of oxidative stress. Increased glucose
      uptake in L6 myotubes was attributed to GLUT 4 translocation, the most downstream
      factor in the insulin signalling cascade, which increased two to threefold on
      chronic pretreatment of quercetin (10 MUM) and rutin (100 MUM).

PMID- 24731382
TI  - Animal shelters: managing heartworms in resource-scarce environments.
AB  - Animal shelters must frequently make difficult decisions regarding the allocation
      of limited resources to appropriately care for the millions of dogs and cats that
      enter their doors annually. Insufficient staffing, expertise, and guidance on
      heartworm management in animal shelters creates significant confusion on how
      these facilities should appropriately address heartworm infection in dogs and
      cats. The American Heartworm Society (AHS) issues comprehensive guidelines for
      the diagnosis, prevention, and management of heartworm infection in pets, but
      shelters are often unable to fully comply with these guidelines due to resource
      constraints. In response, shelter staff is forced to either ignore the disease or
      implement compromised management practices. Such compromises lead to suboptimal
      treatment of infected animals, adoption of infected animals to the public, and
      subsequent backlash from community veterinarians, as well as increased risk of
      disease transmission throughout the shelter and community. Unfortunately, when
      shelters lack the resources to address heartworm infection appropriately, this
      treatable condition may serve as grounds for automatic euthanasia in infected yet
      adoptable animals. The AHS guidelines must be tailored to the needs of sheltering
      agencies or additional resources created to appropriately address the dilemmas
      faced by shelter professionals when managing heartworm disease. 

PMID- 24731383
TI  - Association of antibodies against Neospora caninum in mares with reproductive
      problems and presence of seropositive dogs as a risk factor.
AB  - Sera from 112 mares from 5 horse-breeding farms was examined for the presence of
      antibodies to Neospora caninum and Toxoplasma gondii by an indirect fluorescent
      antibody test (IFAT), as well as from dogs and cattle present on these properties
      for the presence of antibodies to N. caninum. Among the 112 mares, 35 had a
      history of reproductive problems in the last breeding season and 77 had no
      reproductive problems. The rates of seroprevalence of N. caninum in mares with
      and without a history of reproductive problems were 25.71% and 6.49% and from T.
      gondii 2.85% and 1.29%, respectively. In dogs and cattle, the rates of
      seroprevalence of N. caninum were 10.52% and 15.55%, respectively. A positive
      correlation was found between the presence of antibodies against N. caninum
      (p=0.010) in mares and the occurrence of reproductive problems using the Fisher's
      exact test. Significantly higher seroprevalence for N. caninum in mares was
      observed on the farm that had seropositive dogs (p=0.018). Cattle on this farm
      were also seropositive. No significant differences in seropositivity were found
      on farms where dogs were seronegative, or absent. This result suggests, for the
      first time, the presence of seropositive dogs as a risk factor for N. caninum in
      mares and the necessity for further investigation of the epidemiology of this
      parasite in horse-breeding farms with reproductive problems and the presence of
      cattle and dogs. This is the first report on the occurrence of antibodies against
      N. caninum in horses from the state of Santa Catarina, Brazil. 

PMID- 24731384
TI  - Comparison of single-bundle and double-bundle isolated posterior cruciate
      ligament reconstruction with allograft: a prospective, randomized study.
AB  - PURPOSE: The purpose of this study was to evaluate whether posterior cruciate
      ligament reconstruction with the double-bundle (DB) technique improved stability
      of the knee compared with the single-bundle (SB) technique. METHODS: This
      prospective study included 50 patients who were randomized to undergo posterior
      cruciate ligament reconstruction by use of tibialis anterior grafts with either
      the SB technique (25 patients) or DB technique (25 patients). The group
      assignment was concealed before allocation with the use of sealed envelopes.
      Posterior stability was evaluated with the KT-1000 arthrometer (MEDmetric, San
      Diego, CA), and clinical outcomes were assessed with the Lysholm score, Tegner
      activity score, and International Knee Documentation Committee score (both
      objective and subjective). RESULTS: There were 22 patients in the SB group and 24
      patients in the DB group with a minimum follow-up period of 2 years. No
      differences were found between the 2 groups regarding patient demographic data
      and the duration from injury to operation (P > .05). The Lysholm score was 88.0
      +/- 4.2 (range, 83 to 93) in the SB group and 89.8 +/- 3.8 (range, 86 to 95) in
      the DB group, and there was no significant difference between the 2 groups (P =
      .447). The Tegner activity score improved significantly to 6.2 +/- 0.9 (range, 5
      to 8) in the SB group and 6.8 +/- 1.2 (range, 5 to 9) in the DB group. The side
      to-side difference in posterior translation decreased to 4.1 +/- 1.3 mm (range,
      5.5 to 2.5 mm) in the SB group and 2.2 +/- 1.3 mm (range, 4.5 to 2.0 mm) in the
      DB group, and there was a significant difference between the 2 groups (P < .05).
      According to the International Knee Documentation Committee (both objective and
      subjective), the DB group had a better grade distribution (P < .05) and had a
      statistically higher grade (71.6 +/- 6.7; range, 63 to 80) than the SB group
      (65.5 +/- 7.8; range, 56 to 75) (P < .05). CONCLUSIONS: Although both techniques
      resulted in similar patient satisfaction as measured by outcome assessment, the
      DB procedure significantly improved knee stability. LEVEL OF EVIDENCE: Level II,
      lesser-quality randomized controlled trial.

PMID- 24731386
TI  - Does body mass index affect outcomes of ambulatory knee and shoulder surgery?
AB  - PURPOSE: Obesity is highly prevalent among patients with knee and shoulder
      injuries and is associated with greater odds of surgical treatment for these
      injuries. The purpose of this systematic review was to summarize the literature
      that has examined the association between body mass index (BMI) and outcomes of
      ambulatory knee and shoulder surgery. METHODS: A literature search of PubMed and
      Medline was conducted up to December 2013. Studies that examined the association
      between BMI and outcomes after ambulatory knee and shoulder surgery (arthroscopy,
      repairs, and reconstructions) were included. Outcomes included postoperative
      functional scores, clinical scores, and complications. RESULTS: Eighteen studies
      were included in this review; 13 involved knee surgery and 5 involved shoulder
      surgery. Seven knee studies and 2 shoulder studies found increased BMI to be
      associated with worse postoperative outcomes, whereas the remaining 9 studies did
      not find an association. Increased BMI was associated with worse clinical scores
      and less patient satisfaction after arthroscopic meniscectomy or debridement, and
      with worse clinical scores and lower activity levels after anterior cruciate
      ligament (ACL) reconstruction. It was also associated with worse clinical scores
      and a longer hospital stay after rotator cuff repair and with longer time to
      return to work after subacromial decompression. Six studies examined the
      association between BMI and complications, but all reported null findings.
      CONCLUSIONS: There is a lack of consensus in the literature regarding the
      association between BMI and ambulatory knee and shoulder surgery. Several factors
      may have contributed to contradictory findings, including variation in measuring
      and classifying anthropometry, postoperative outcomes, and follow-up time. LEVEL
      OF EVIDENCE: Level IV, systematic review of Level I, III, and IV studies.

PMID- 24731385
TI  - Surgical treatment of posterolateral rotatory instability of the elbow.
AB  - PURPOSE: The purpose of this systematic review was to critically examine the
      outcomes of lateral ulnar collateral ligament reconstruction for posterolateral
      rotatory instability (PLRI) of the elbow. METHODS: A systematic review of the
      literature was performed. Two reviewers assessed and confirmed the methodologic
      and patient data from the included studies. Frequency-weighted means were
      calculated for outcomes that were present in multiple studies. RESULTS: Eight
      studies fulfilled our criteria, and they included 130 patients. The mean age was
      38.1 years, and the mean follow-up period was 44.5 months. Traumatic dislocation
      was the most common cause of PLRI. Of the studies that reported the Mayo Elbow
      Performance Score, 91% of patients had good or excellent results, with a
      frequency-weighted mean of 91. Improvement in elbow range of motion was noted
      (133 degrees  to 138 degrees  of flexion [P < .0001] and 6.6 degrees  to 3.9
      degrees  of extension [P = .005]). A complication rate of 11% was noted, with
      recurrent instability noted to occur in 8% of patients. CONCLUSIONS: PLRI of the
      elbow remains to be fully understood. Treatment strategies vary and should be
      performed based on surgeon experience and evidence available. Most patients will
      have good or excellent results after surgery; however, up to 11% of patients may
      have complications. LEVEL OF EVIDENCE: Level IV, systematic review of Level II
      through IV studies.

PMID- 24731387
TI  - Designing and evaluating the MULTICOM protein local and global model quality
      prediction methods in the CASP10 experiment.
AB  - BACKGROUND: Protein model quality assessment is an essential component of
      generating and using protein structural models. During the Tenth Critical
      Assessment of Techniques for Protein Structure Prediction (CASP10), we developed
      and tested four automated methods (MULTICOM-REFINE, MULTICOM-CLUSTER, MULTICOM
      NOVEL, and MULTICOM-CONSTRUCT) that predicted both local and global quality of
      protein structural models. RESULTS: MULTICOM-REFINE was a clustering approach
      that used the average pairwise structural similarity between models to measure
      the global quality and the average Euclidean distance between a model and several
      top ranked models to measure the local quality. MULTICOM-CLUSTER and MULTICOM
      NOVEL were two new support vector machine-based methods of predicting both the
      local and global quality of a single protein model. MULTICOM-CONSTRUCT was a new
      weighted pairwise model comparison (clustering) method that used the weighted
      average similarity between models in a pool to measure the global model quality.
      Our experiments showed that the pairwise model assessment methods worked better
      when a large portion of models in the pool were of good quality, whereas single
      model quality assessment methods performed better on some hard targets when only
      a small portion of models in the pool were of reasonable quality. CONCLUSIONS:
      Since digging out a few good models from a large pool of low-quality models is a
      major challenge in protein structure prediction, single model quality assessment
      methods appear to be poised to make important contributions to protein structure
      modeling. The other interesting finding was that single-model quality assessment
      scores could be used to weight the models by the consensus pairwise model
      comparison method to improve its accuracy.

PMID- 24731388
TI  - [Advances in bone dysplasias].
AB  - The prevalence of bone dysplasias is estimated to be one case per 1,000
      inhabitants, which suggests that, at some point in the career of an orthopaedic
      surgeon, he will face with one of these patients. The aim of this paper is to
      review the general aspects of bone dysplasias and focus on those, which due to
      their frequency and importance, we consider most relevant (achondroplasia,
      multiple epiphyseal dysplasia, spondyloepiphyseal dysplasia, osteogenesis
      imperfecta), reviewing their fundamental features and the latest therapeutic
      advances. There is no cure for these diseases, so early diagnosis and appropriate
      therapeutic management, becomes the key to improving quality of life of these
      patients. 

PMID- 24731389
TI  - 200th ENMC International Workshop "European reference networks: recommendations
      and criteria in the neuromuscular field", 18-20 October 2013, Naarden, The
      Netherlands.

PMID- 24731390
TI  - Multicystic dysplastic kidney: Impact of imaging modality selection on the
      initial management and prognosis.
AB  - OBJECTIVE: To evaluate the impact of imaging modalities on the evaluation and
      prognosis of children with multicystic dysplastic kidney (MCDK) disease. PATIENTS
      AND METHODS: A retrospective analysis of all children with MCDK diagnosed from
      2004 until 2012 was performed. The study included 63 patients for whom all
      postnatal imaging modalities were available: renal bladder ultrasound (RBUS),
      dimercaptosuccinic acid scan (DMSA) and voiding cystourethrogram (VCUG). Cases
      with major congenital abnormalities or incomplete data were excluded.
      Abnormalities in the contralateral kidney and the fate of MCDK were also
      addressed. RESULTS: At diagnosis, the average age was four-and-a-half months. The
      majority of cases were detected antenatally (87%). Postnatal RBUS and DMSA scans
      established the diagnosis of MCDK in 92% and 98% of patients, respectively. DMSA
      showed photopenic areas in the contralateral kidneys in 10% of patients; all of
      them had hydronephrosis and were confirmed to have vesicoureteral reflux (VUR).
      Contralateral VUR was detected in 16 patients; 63% of them had hydronephrosis.
      After a mean follow-up of three-and-a-half years, involution occurred in 62% of
      patients and the involution rate was inversely proportional to the initial size.
      CONCLUSIONS: The classical appearance of MCDK on RBUS was sufficient to establish
      the diagnosis in most patients. DMSA scan was more accurate in confirming the
      diagnosis and evaluating the contralateral kidney. Selective screening for VUR in
      patients with contralateral hydronephrotic kidney should be considered.

PMID- 24731391
TI  - [Usefulness of corrective make-up in children with vitiligo coordinated by
      dermatology nursing].
AB  - There are certain skin disorders such as vitiligo, acne, vascular malformations
      and postoperative scars that can affect the quality of life of children and
      especially adolescents. It can become an obstacle to their psychosocial
      development. A review was conducted on 4 patients with vitiligo located on face,
      who took part in a camouflage treatment course from January to December 2012. The
      impact of the skin disorder on quality of life was assessed before and after the
      therapeutic make-up sessions. Corrective makeup can be a complementary,
      reproducible, cost-effective, non-invasive, and useful technique in the
      management of dermatological diseases that have a physical and emotional impact
      in childhood. 

PMID- 24731392
TI  - Basic life support knowledge, self-reported skills and fears in Danish high
      school students and effect of a single 45-min training session run by junior
      doctors; a prospective cohort study.
AB  - BACKGROUND: Early recognition and immediate bystander cardiopulmonary
      resuscitation are critical determinants of survival after out-of-hospital cardiac
      arrest (OHCA). Our aim was to evaluate current knowledge on basic life support
      (BLS) in Danish high school students and benefits of a single training session
      run by junior doctors. METHODS: Six-hundred-fifty-one students were included.
      They underwent one 45-minute BLS training session including theoretical aspects
      and hands-on training with mannequins. The students completed a baseline
      questionnaire before the training session and a follow-up questionnaire one week
      later. The questionnaire consisted of an eight item multiple-choice test on BLS
      knowledge, a four-level evaluation of self-assessed BLS skills and evaluation of
      fear based on a qualitative description and visual analog scale from 0 to 10 for
      being first responder. RESULTS: Sixty-three percent of the students (413/651) had
      participated in prior BLS training. Only 28% (179/651) knew how to correctly
      recognize normal breathing. The majority was afraid of exacerbating the condition
      or causing death by intervening as first responder. The response rate at follow
      up was 61% (399/651). There was a significant improvement in correct answers on
      the multiple-choice test (p < .001). The proportion of students feeling well
      prepared to perform BLS increased from 30% to 90% (p < .001), and the level of
      fear of being first responder was decreased 6.8 +/- 2.2 to 5.5 +/- 2.4 (p <
      .001). CONCLUSION: Knowledge of key areas of BLS is poor among high school
      students. One hands-on training session run by junior doctors seems to be
      efficient to empower the students to be first responders to OHCA.

PMID- 24731393
TI  - Comparison of 3-Factor Prothrombin Complex Concentrate and Low-Dose Recombinant
      Factor VIIa for Warfarin Reversal.
AB  - INTRODUCTION: Prothrombin complex concentrate (PCC) and recombinant Factor VIIa
      (rFVIIa) have been used for emergent reversal of warfarin anticoagulation. Few
      clinical studies have compared these agents in warfarin reversal. We compared
      warfarin reversal in patients who received either 3 factor PCC (PCC3) or low-dose
      rFVIIa (LDrFVIIa) for reversal of warfarin anticoagulation. METHODS: Data were
      collected from medical charts of patients who received at least one dose of PCC3
      (20 units/kg) or LDrFVIIa (1000 or 1200 mcg) for emergent warfarin reversal from
      August 2007 to October 2011. The primary end-points were achievement of an INR
      1.5 or less for efficacy and thromboembolic events for safety. RESULTS: Seventy
      four PCC3 and 32 LDrFVIIa patients were analyzed. Baseline demographics, reason
      for warfarin reversal, and initial INR were equivalent. There was no difference
      in the use of vitamin K or fresh frozen plasma. More LDrFVIIa patients achieved
      an INR of 1.5 or less (71.9% vs. 33.8%, p =0.001). The follow-up INR was lower
      after LDrFVIIa (1.25 vs. 1.75, p < 0.05) and the percent change in INR was larger
      after LDrFVIIa (54.1% vs. 38.8%, p = 0.002). There was no difference in the
      number of thromboembolic events (2 LDrFVIIa vs. 5 PCC3, p = 1.00), mortality,
      length of hospital stay, or cost. CONCLUSIONS: Based on achieving a goal INR of
      1.5 or less, LDrFVIIa was more likely than PCC3 to reverse warfarin
      anticoagulation. Thromboembolic events were equivalent in patients receiving PCC3
      and LDrFVIIa.

PMID- 24731394
TI  - Antimicrobial susceptibility pattern of bacterial isolates from wound infection
      and their sensitivity to alternative topical agents at Jimma University
      Specialized Hospital, South-West Ethiopia.
AB  - BACKGROUND: Wound infection is one of the health problems that are caused and
      aggravated by the invasion of pathogenic organisms. Information on local
      pathogens and sensitivity to antimicrobial agents, and topical agents like acetic
      acid is crucial for successful treatment of wounds. OBJECTIVES: To determine
      antimicrobial susceptibility pattern of bacterial isolates from wound infection
      and their sensitivity to alternative topical agents at Jimma University
      Specialized Hospital. METHODS: A cross sectional study was conducted among
      patients with wound infection visiting Jimma University Specialized Hospital,
      from May to September 2013. Wound swab was collected using sterile cotton swabs
      and processed for bacterial isolation and susceptibility testing to antimicrobial
      agents, acetic acid, hydrogen peroxide and dabkin solution following standard
      bacteriological techniques. Biochemical tests were done to identify the species
      of the organisms. Sensitivity testing was done using Kirby- Baur disk diffusion
      method. Minimum inhibitory and bactericidal concentration was done using tube
      dilution method. RESULTS: In this study 145 bacterial isolates were recovered
      from 150 specimens showing an isolation rate of 87.3%. The predominant bacteria
      isolated from the infected wounds were Staphylococcus aureus 47 (32.4%) followed
      by Escherichia coli 29 (20%), Proteus species 23 (16%), Coagulase negative
      Staphylococci 21 (14.5%), Klebsiella pneumoniae 14 (10%) and Pseudomonas
      aeruginosa 11 (8%). All isolates showed high frequency of resistance to
      ampicillin, penicillin, cephalothin and tetracycline. The overall multiple drug
      resistance patterns were found to be 85%. Acetic acid (0.5%), Dabkin solution
      (1%) and 3% hydrogen peroxide were bactericidal to all isolated bacteria and
      lethal effect observed when applied for 10 minutes. CONCLUSIONS: On in vitro
      sensitivity testing, ampicillin, penicillin, cephalothin and tetracycline were
      the least effective. Gentamicin, norfloxacin, ciprofloxacin, vancomycin and
      amikacin were the most effective antibiotics. Acetic acid (0.5%), dabkin solution
      (1%) and H2O2 (3%) were bactericidal to all isolates.

PMID- 24731395
TI  - Growth kinetics of Staphylococcus aureus on Brie and Camembert cheeses.
AB  - In this study, we developed mathematical models to describe the growth kinetics
      of Staphylococcus aureus on natural cheeses. A five-strain mixture of Staph.
      aureus was inoculated onto 15 g of Brie and Camembert cheeses at 4 log CFU/g. The
      samples were then stored at 4, 10, 15, 25, and 30  degrees C for 2-60 d, with a
      different storage time being used for each temperature. Total bacterial and
      Staph. aureus cells were enumerated on tryptic soy agar and mannitol salt agar,
      respectively. The Baranyi model was fitted to the growth data of Staph. aureus to
      calculate kinetic parameters such as the maximum growth rate in log CFU units (r
      max; log CFU/g/h) and the lag phase duration (lambda; h). The effects of
      temperature on the square root of r max and on the natural logarithm of lambda
      were modelled in the second stage (secondary model). Independent experimental
      data (observed data) were compared with prediction and the respective root mean
      square error compared with the RMSE of the fit on the original data, as a measure
      of model performance. The total growth of bacteria was observed at 10, 15, 25,
      and 30  degrees C on both cheeses. The r max values increased with storage
      temperature (P<0.05), but a significant effect of storage temperature on lambda
      values was only observed between 4 and 15  degrees C (P<0.05). The square root
      model and linear equation were found to be appropriate for description of the
      effect of storage temperature on growth kinetics (R 2=0.894-0.983). Our results
      indicate that the models developed in this study should be useful for describing
      the growth kinetics of Staph. aureus on Brie and Camembert cheeses. 

PMID- 24731396
TI  - A triple risk model for unexplained late stillbirth.
AB  - BACKGROUND: The triple risk model for sudden infant death syndrome (SIDS) has
      been useful in understanding its pathogenesis. Risk factors for late stillbirth
      are well established, especially relating to maternal and fetal wellbeing.
      DISCUSSION: We propose a similar triple risk model for unexplained late
      stillbirth. The model proposed by us results from the interplay of three groups
      of factors: (1) maternal factors (such as maternal age, obesity, smoking), (2)
      fetal and placental factors (such as intrauterine growth retardation, placental
      insufficiency), and (3) a stressor (such as venocaval compression from maternal
      supine sleep position, sleep disordered breathing). We argue that the risk
      factors within each group in themselves may be insufficient to cause the death,
      but when they interrelate may produce a lethal combination. SUMMARY: Unexplained
      late stillbirth occurs when a fetus who is somehow vulnerable dies as a result of
      encountering a stressor and/or maternal condition in a combination which is
      lethal for them.

PMID- 24731397
TI  - PRP19 upregulation inhibits cell proliferation in lung adenocarcinomas by p21
      mediated induction of cell cycle arrest.
AB  - Precursor messenger RNA processing factor 19 (PRP19) is known to be a critical
      component of the eukaryotic spliceosomal machinery and DNA damage repair system,
      the deregulation of which leads to many disease conditions. In many human
      cancers, PRP19 expression is upregulated, but its functional significance and
      corresponding underlying mechanisms remain to be addressed. Focusing on lung
      carcinomas, PRP19 upregulation was achieved by plasmid transfection into A549
      adenocarcinoma cells. The transfected cells were then subjected to several in
      vitro and in vivo assays following in situ assessment of the protein in paired
      clinical lung tissues. We report that PRP19 expression is elevated in lung
      carcinoma tissues compared to non-tumor tissues. Following its upregulation,
      PRP19 repressed cell proliferation and tumor growth by upregulating the
      expression of the cell cycle arrest protein p21. 

PMID- 24731398
TI  - Mitochondrial oxidative phosphorylation TRAP(1)ped in tumor cells.
AB  - Many tumors undergo a dramatic metabolic shift known as the Warburg effect in
      which glucose utilization is favored and oxidative phosphorylation is
      downregulated, even when oxygen availability is plentiful. However, the
      mechanistic basis for this switch has remained unclear. Recently several
      independent groups identified tumor necrosis factor receptor-associated protein 1
      (TRAP1), a mitochondrial molecular chaperone of the heat shock protein 90 (Hsp90)
      family, as a key modulator of mitochondrial respiration. Although all reports
      agree that this activity of TRAP1 has important implications for neoplastic
      progression, data from the different groups only partially overlap, suggesting
      that TRAP1 may have complex and possibly contextual effects on tumorigenesis. In
      this review we analyze these recent findings and attempt to reconcile these
      observations. 

PMID- 24731399
TI  - Low birth weight, preterm birth or small-for-gestational-age are not associated
      with dental caries in young Japanese children.
AB  - BACKGROUND: Low birth weight (LBW) continues to increase and is a major public
      health problem in Japan. In the present cross-sectional study, we examined the
      associations between LBW, preterm birth and small-for-gestational-age (SGA) and
      the prevalence of dental caries in young Japanese children. METHODS: Study
      subjects were 2,055 children aged 3 years. Data on birth conditions were obtained
      through the transcription by parents or guardians of the information from their
      maternal and child health handbook, in which the data were recorded by staff at
      the birth hospital or clinic, to our self-administered questionnaire. Children
      were classified as having caries if one or more deciduous teeth were decayed,
      missing, or had been filled at the time of examination. Adjustments were made for
      sex, toothbrushing frequency, use of fluoride, regular dental check-ups, between
      meal snack frequency, breastfeeding duration, paternal and maternal educational
      levels, maternal smoking during pregnancy, and secondhand smoke exposure at home.
      RESULTS: The prevalence of dental caries was 20.7%. The mean birth weight was
      3018.3 g, and 8.3% were classified as LBW (<2,500 g), 4.5% as preterm birth (<37
      weeks), and 7.1% as SGA (<10th percentile). Preterm birth was associated with a
      40% decreased prevalence of dental caries (adjusted prevalence ratio = 0.60, 95%
      confidence interval: 0.36-1.02, p = 0.06). There were no associations between LBW
      or SGA and the prevalence of dental caries. CONCLUSIONS: The results of the study
      failed to detect significant associations between LBW, preterm birth or SGA and
      the prevalence of dental caries in Japan. Further study is needed in other
      populations to confirm the generalizability of these findings.

PMID- 24731400
TI  - Three countries-half of the global cancer burden.

PMID- 24731401
TI  - Strengthening cancer control in China.

PMID- 24731402
TI  - A health-system response to cancer in India.

PMID- 24731403
TI  - Cancer in Russia: reflections from WHO in Europe.

PMID- 24731404
TI  - Challenges to effective cancer control in China, India, and Russia.
AB  - Cancer is one of the major non-communicable diseases posing a threat to world
      health. Unfortunately, improvements in socioeconomic conditions are usually
      associated with increased cancer incidence. In this Commission, we focus on
      China, India, and Russia, which share rapidly rising cancer incidence and have
      cancer mortality rates that are nearly twice as high as in the UK or the USA,
      vast geographies, growing economies, ageing populations, increasingly westernised
      lifestyles, relatively disenfranchised subpopulations, serious contamination of
      the environment, and uncontrolled cancer-causing communicable infections. We
      describe the overall state of health and cancer control in each country and
      additional specific issues for consideration: for China, access to care,
      contamination of the environment, and cancer fatalism and traditional medicine;
      for India, affordability of care, provision of adequate health personnel, and
      sociocultural barriers to cancer control; and for Russia, monitoring of the
      burden of cancer, societal attitudes towards cancer prevention, effects of
      inequitable treatment and access to medicine, and a need for improved
      international engagement. 

PMID- 24731405
TI  - [Radiotherapy plus concomitant systemic therapies for patients with brain
      metastases from breast cancer].
AB  - The incidence of brain metastases from breast cancer is increasing with diagnosis
      and therapeutics progress, especially with systemic therapies. The occurrence of
      multiple brain metastases remains a delicate situation when surgery and
      stereotactic radiosurgery are not indicated, nor available. Treatment strategy is
      based on the patient's general condition and extracranial disease status. Whole
      brain radiation therapy remains the gold standard local treatment but its
      efficacy is limited with a median overall survival of 6 months. New strategies
      are needed for increasing survival and patients' quality of life. Combining
      radiation therapy and chemotherapy has been a subject of interest. This article
      sums up the different radiotherapy plus concomitant systemic therapies
      combinations for the treatment of brain metastases from breast cancer.

PMID- 24731406
TI  - Goal-directed transfusion protocol via thrombelastography in patients with
      abdominal trauma: a retrospective study.
AB  - INTRODUCTION: The optimal transfusion protocol remains unknown in the trauma
      setting. This retrospective cohort study aimed to determine if goal-directed
      transfusion protocol based on standard thrombelastography (TEG) is feasible and
      beneficial in patients with abdominal trauma. METHODS: Sixty adult patients with
      abdominal trauma who received 2 or more units of red blood cell transfusion
      within 24 hours of admission were studied. Patients managed with goal-directed
      transfusion protocol via TEG (goal-directed group) were compared to patients
      admitted before utilization of the protocol (control group). RESULTS: There were
      29 patients in the goal-directed group and 31 in the control group. Baseline
      parameters were similar except for higher admission systolic blood pressure in
      the goal-directed group than the control group (121.8 +/- 23.1 mmHg vs 102.7 +/-
      26.5 mmHg, p < 0.01). At 24 h, patients in the goal-directed group had shorter
      aPTT compared to patients in the control group (39.2 +/- 16.3 s vs 58.6 +/- 36.6
      s, p = 0.044). Administration of total blood products at 24 h appeared to be
      fewer in the goal-directed group than the control group (10.2 [7.0-43.1]U vs 14.8
      [8.3-37.6]U, p = 0.28), but this was not statistically significant. Subgroup
      analysis including patients with ISS >=16 showed that patients in the goal
      directed group had significantly fewer consumption of total blood products than
      patients in the control group (7[6.1, 47.0]U vs 37.6[14.5, 89.9]U, p = 0.015). No
      differences were found in mortality at 28d, length of stay in intensive care unit
      and hospital between the two groups. CONCLUSIONS: Goal-directed transfusion
      protocol via standard TEG was achievable in patients with abdominal trauma. The
      novel protocol, compared to conventional transfusion management, has the
      potential to decrease blood product utilization and prevent exacerbation of
      coagulation function.

PMID- 24731407
TI  - Astragaloside IV attenuates allergic inflammation by regulation Th1/Th2 cytokine
      and enhancement CD4(+)CD25(+)Foxp3 T cells in ovalbumin-induced asthma.
AB  - Astragaloside IV is the chief ingredient of Radix Astragali, which has been used
      in the Traditional Chinese Medicine as a major component of many polyherbal
      formulations for the repair and regeneration of injured organ and tissues. We
      tested the anti-asthmatic effects of AST IV and the possible mechanisms. BALB/c
      mice that were sensitized and challenged to ovalbumin (OVA) were treated with AST
      IV (40mg/kg and 20mg/kg) 1h before they were challenged with OVA. Our study
      demonstrated that AST IV inhibited OVA-induced increases in eosinophil count;
      interleukin (IL)-4 level were recovered in bronchoalveolar lavage fluid increased
      IFN-gamma and IL-10 levels in bronchoalveolar lavage fluid. Histological studies
      demonstrated that AST IV substantially inhibited OVA-induced eosinophilia in lung
      tissue. Flow cytometry studies demonstrated that AST IV substantially increased
      CD4(+)CD25(+)Foxp3 T cells (Treg). Furthermore quantitative real-time (qPCR)
      studies demonstrated that AST IV substantially enhanced Foxp3 mRNA expression in
      lung tissue. These findings suggest that AST IV may effectively ameliorate the
      progression of airway inflammation and could be used as a therapy for patients
      with allergic inflammation. 

PMID- 24731408
TI  - Surgical leadership in the time of significant generational diversity.

PMID- 24731409
TI  - Perceptions of individuals living with spinal cord injury toward preference-based
      quality of life instruments: a qualitative exploration.
AB  - BACKGROUND: Generic preference-based health-related quality of life instruments
      are widely used to measure health benefit within economic evaluation. The
      availability of multiple instruments raises questions about their relative merits
      and recent studies have highlighted the paucity of evidence regarding measurement
      properties in the context of spinal cord injury (SCI). This qualitative study
      explores the views of individuals living with SCI towards six established
      instruments with the objective of identifying 'preferred' outcome measures (from
      the perspective of the study participants). METHODS: Individuals living with SCI
      were invited to participate in one of three focus groups. Eligible participants
      were identified from Vancouver General Hospital's Spine Program database;
      purposive sampling was used to ensure representation of different demographics
      and injury characteristics. Perceptions and opinions were solicited on the
      following questionnaires: 15D, Assessment of Quality of Life 8-dimension (AQoL
      8D), EQ-5D-5L, Health Utilities Index (HUI), Quality of Well-Being Scale Self
      Administered (QWB-SA), and the SF-36v2. Framework analysis was used to analyse
      the qualitative information gathered during discussion. Strengths and limitations
      of each questionnaire were thematically identified and managed using NVivo 9
      software. RESULTS: Major emergent themes were (i) general perceptions, (ii)
      comprehensiveness, (iii) content, (iv) wording and (v) features. Two sub-themes
      pertinent to content were also identified; 'questions' and 'options'. All focus
      group participants (n = 15) perceived the AQoL-8D to be the most relevant
      instrument to administer within the SCI population. This measure was considered
      to be comprehensive, with relevant content (i.e. wheelchair inclusive) and
      applicable items. Participants had mixed perceptions about the other
      questionnaires, albeit to varying degrees. CONCLUSIONS: Despite a strong
      theoretical underpinning, the AQoL-8D (and other AQoL instruments) is
      infrequently used outside its country of origin (Australia). Empirical
      comparative analyses of the favoured instruments identified in this qualitative
      study are necessary within the context of spinal cord injury.

PMID- 24731410
TI  - Obstetric interventions in two groups of hospitals in Catalonia: a cross
      sectional study.
AB  - BACKGROUND: Childbirth assistance in highly technological settings and existing
      variability in the interventions performed are cause for concern. In recent
      years, numerous recommendations have been made concerning the importance of the
      physiological process during birth. In Spain and Catalonia, work has been carried
      out to implement evidence-based practices for childbirth and to reduce
      unnecessary interventions.To identify obstetric intervention rates among all
      births, determine whether there are differences in interventions among full-term
      single births taking place in different hospitals according to type of funding
      and volume of births attended to, and to ascertain whether there is an
      association between caesarean section or instrumental birth rates and type of
      funding, the volume of births attended to and women's age. METHODS: Cross
      sectional study, taking the hospital as the unit of analysis, obstetric
      interventions as dependent variables, and type of funding, volume of births
      attended to and maternal age as explanatory variables. The analysis was performed
      in three phases considering all births reported in the MBDS Catalonia 2011
      (7,8570 births), full-term single births and births coded as normal. RESULTS: The
      overall caesarean section rate in Catalonia is 27.55% (CI 27.23 to 27.86). There
      is a significant difference in caesarean section rates between public and private
      hospitals in all strata. Both public and private hospitals with a lower volume of
      births have higher obstetric intervention rates than other hospitals (49.43%, CI
      48.04 to 50.81). CONCLUSIONS: In hospitals in Catalonia, both the type of funding
      and volume of births attended to have a significant effect on the incidence of
      caesarean section, and type of funding is associated with the use of instruments
      during delivery.

PMID- 24731411
TI  - A framework for implementation, education, research and clinical use of
      ultrasound in emergency departments by the Danish Society for Emergency Medicine.
AB  - The first Danish Society for Emergency Medicine (DASEM) recommendations for the
      use of clinical ultrasound in emergency departments has been made. The
      recommendations describes what DASEM believes as being current best practice for
      training, certification, maintenance of acquired competencies, quality assurance,
      collaboration and research in the field of clinical US used in an ED. 

PMID- 24731412
TI  - Variations in vital signs in the last days of life in patients with advanced
      cancer.
AB  - CONTEXT: Few studies have examined variation in vital signs in the last days of
      life. OBJECTIVES: We determined the variation of vital signs in the final two
      weeks of life in patients with advanced cancer and examined their association
      with impending death in three days. METHODS: In this prospective, longitudinal,
      observational study, we enrolled consecutive patients admitted to two acute
      palliative care units and documented their vital signs (heart rate, blood
      pressure, respiratory rate, oxygen saturation, and temperature) twice a day
      serially from admission to death or discharge. RESULTS: Of 357 patients, 203
      (57%) died in hospital. Systolic blood pressure (P < 0.001), diastolic blood
      pressure (P < 0.001), and oxygen saturation (P < 0.001) decreased significantly
      in the final three days of life, and temperature increased slightly (P < 0.04).
      Heart rate (P = 0.22) and respiratory rate (P = 0.24) remained similar in the
      last three days. Impending death in three days was significantly associated with
      increased heart rate (odds ratio [OR] = 2; P = 0.01), decreased systolic blood
      pressure (OR = 2.5; P = 0.004), decreased diastolic blood pressure (OR = 2.3; P =
      0.002), and decreased oxygen saturation (OR = 3.7; P = 0.003) from baseline
      readings on admission. These changes had high specificity (>= 80%), low
      sensitivity (<= 35%), and modest positive likelihood ratios (<= 5) for impending
      death within three days. A large proportion of patients had normal vital signs in
      the last days of life. CONCLUSION: Blood pressure and oxygen saturation decreased
      in the last days of life. Clinicians and families cannot rely on vital sign
      changes alone to rule in or rule out impending death. Our findings do not support
      routine vital signs monitoring of patients who are imminently dying.

PMID- 24731413
TI  - Intensive care nurses' perceptions of simulation-based team training for building
      patient safety in intensive care: a descriptive qualitative study.
AB  - OBJECTIVES: To describe intensive care nurses' perceptions of simulation-based
      team training for building patient safety in intensive care. BACKGROUND: Failures
      in team processes are found to be contributory factors to incidents in an
      intensive care environment. Simulation-based training is recommended as a method
      to make health-care personnel aware of the importance of team working and to
      improve their competencies. DESIGN: The study uses a qualitative descriptive
      design. METHODS: Individual qualitative interviews were conducted with 18
      intensive care nurses from May to December 2009, all of which had attended a
      simulation-based team training programme. The interviews were analysed by
      qualitative content analysis. RESULTS: One main category emerged to illuminate
      the intensive care nurse perception: "training increases awareness of clinical
      practice and acknowledges the importance of structured work in teams". Three
      generic categories were found: "realistic training contributes to safe care",
      "reflection and openness motivates learning" and "finding a common understanding
      of team performance". CONCLUSIONS: Simulation-based team training makes intensive
      care nurses more prepared to care for severely ill patients. Team training
      creates a common understanding of how to work in teams with regard to patient
      safety.

PMID- 24731414
TI  - [Enhanced Depth Imaging- optical coherence tomography technique and the lamina
      cribrosa in glaucoma].

PMID- 24731415
TI  - [Change of masticatory movement in cleft lip and palate patients with anterior
      crossbite before and after maxillary protraction].
AB  - OBJECTIVE: To quantitatively measure the masticatory movement and to investigate
      the change of stomatognathic function in patients with cleft lip and palate.
      METHODS: Fifteen patients with complete cleft lip and palate were
      selected.Electromyography of bilateral anterior temporalis and masseter was
      measured and mandibular movement was examined during masticatory movement before
      and after maxillary protraction. RESULTS: After treatment, the activity of
      masticatory muscles in the functional side was increased significantly.In the
      unilateral mastication side (left) and the right side, the activities of anterior
      temporalis increased from 45.57 (26.75, 67.84) mV to 80.24 (72.31, 91.36) mV and
      from 45.25 (37.34, 57.42) mV to 73.56 (59.63, 94.80) mV, respectively.In the
      unilateral mastication side (left)and the right side, the activities of masseter
      increased from 62.37 (45.76, 72.45) mV to 90.35 (78.94, 110.45) mV and from 67.53
      (59.65, 80.53) mV to 87.97 (72.35, 99.79) mV, respectively.No significant
      increment in the balance side was found during masticatory movement. The
      masticatory trajectory was not changed significantly. The width of lateral and
      vertical scale of right side mastication increased significantly (P < 0.05).
      CONCLUSIONS: After the treatment, the activity of masticatory muscles increased
      significantly, and the width of lateral and vertical scale of right side
      mastication increased significantly.

PMID- 24731416
TI  - [Therapeutic effects of oral appliance combined with uvulopalatopharyngoplasty on
      obstructive sleep apnea hypopnea syndrome].
AB  - OBJECTIVE: To explore the long-term effects of the uvulopalatopharyngoplasty
      (UPPP) combined with oral appliance (OA) in the treatment of obstructive sleep
      apnea hypopnea syndrome (OSAHS). METHODS: Thirty patients with severe OSAHS
      confirmed by polysomnography (PSG) according to their apnea hypopnea index (AHI)
      and lowest SaO2 during sleep were selected using random permutation table and
      divided into only UPPP group(U group, n = 15) and UPPP with OA group (UA group, n
      = 15). The follow-up period was 2 years. PSG was performed in 0.5 year and 2
      years after operation. AHI, lowest SaO2 and Tmax were tested and evaluated.
      RESULTS: The effectiveness of two groups was the same after 0.5 year. Two years
      after operation, the values [AHI: (18.06 +/- 2.24) times/h; lowest SaO2: (88.64
      +/- 10.37)% and Tmax: (20.5 +/- 17.6) s] in UA group were better than that [AHI:
      (49.73 +/- 3.35) times/h; lowest SaO2: (79.56 +/- 4.87)% and Tmax: (41.3 +/-
      19.7) s] in U group. The number of effectiveness was 9 and the number of
      ineffectiveness was 6 in U group, while in UA group, the number of effectiveness
      was 14 and the number of ineffectiveness was 1(P < 0.05). CONCLUSIONS: Long-term
      result of combined treatment was better than that of UPPP only.

PMID- 24731417
TI  - [Association of CD(+)4 T lymphocyte count and gingival crevicular fluid
      prostaglandin E2 with periodontal parameters in HIV-positive periodontitis
      patients].
AB  - OBJECTIVE: To investigate the correlation of CD(+)4 T lymphocyte count and
      prostaglandin E2 (PGE2) in gingival crevicular fluid (GCF) with periodontal
      status in HIV-positive patients with periodontitis. METHODS: Twenty subjects were
      selected according to inclusion criteria. The plasmatic CD(+)4 T lymphocytes were
      counted. All the individuals were divided into three groups, group A (CD(+)4 T
      lymphocyte count < 200 cell/mm(3)), group B (200 cell/mm(3) <= CD(+)4 T
      lymphocyte count <= 500 cell/mm(3)) and group C (CD(+)4 T lymphocyte count > 500
      cell/mm(3)). Periodontal indexes, including plaque index(PLI), bleeding
      index(BI), attachment level(AL) and probing depth(PD) were recorded.GCF samples
      were taken from 120 index teeth by means of sterile paper strips.GCF PGE2 levels
      were determined by radioimmunoassays. Mann-Whitney was used to compare the
      periodontal indexes and PGE2 levels among the three groups. Partial correlations
      and Spearman correlations were applied to analyze the correlation of CD(+)4 T
      lymphocytes count and PGE2 in gingival crevicular fluid with periodontal status.
      RESULTS: BI value, PGE2 concentration and total PGE2 were 3.00(2.00),
      90.75(30.60) ug/L, 447.58 (243.08) pg in group B, which were higher than those in
      group A[2.00(1.25), 79.75(30.50) ug/L and 339.52 (200.97) pg respectively] and
      group C[2.00(1.00), 73.38 (14.83) ug/L and 299.18 (108.33) pg respectively] (P <
      0.0167). But the differences of PD and AL among the three groups were not
      significantly different(P > 0.0167). The correlations were observed between
      CD(+)4 T lymphocyte count and BI for the subpopulations with CD(+)4 T lymphocyte
      count <200 cells/mm(3) (r = 0.657, P < 0.05) and between 200-500 cells/mm(3) (r =
      -0.369, P < 0.05). PGE2 concentration was negatively correlated with BI, PD and
      AL (P < 0.05), and total PGE2 was positively correlated with PD and AL(P < 0.05).
      CONCLUSIONS: There was an association between the periodontal status and CD(+)4 T
      lymphocyte count in HIV(+) patients.GCF PGE2 level was related to periodontal
      parameters including BI, PD and AL.

PMID- 24731418
TI  - [The comparison of the ability of polysaccharide from different Porphyromonas
      gingivalis in inducing THP-1 cells to produce cytokines].
AB  - OBJECTIVE: To compare the ability of the polysaccharide from various
      Porphyromonas gingivalis (Pg) type and clinical strains in inducing THP-1 cells
      to produce cytokines interleukin(IL)-1beta, IL-8, and tumor necrosis factor(TNF)
      alpha, in order to analyze the immunogenicity of Pg polysaccharide components and
      the virulence-associated factors of this periodontal pathogen. METHODS: The
      bacterial polysaccharide was extracted from high virulent Pg strains, W83, SJD2,
      SJD12 and low virulent Pg, ATCC33277, SJD4, SJD5, and SJD11 by phenol-water
      extraction. The extracted polysaccharide was used to stimulate the THP-1 cells
      with different simulation periods and doses. The level of the cytokines,
      including IL-1beta,IL-8 and TNF-alpha in the cell culture suspension was measured
      by enzyme-linked immunosorbent assay(ELISA). RESULTS: The polysaccharide
      extraction of Pg strains was composed of lipopolysaccharide(LPS) and capsular
      polysaccharide. The secretion of IL-1beta, IL-8 and TNF-alpha, produced by the
      THP-1 cells showed in a time- and dose-dependent manner in the medium containing
      10% fetal bovine serum. The level of these cytokines of the high virulent strains
      was higher than that of the low virulent strains in medium containing 1% fetal
      bovine serum.Four hours after stimulation with polysaccharide extracted from high
      virulent strains, the levels of IL-1beta,IL-8, and TNF-alpha in the cell
      suspension were (1 639 +/- 497), (1 648 +/- 513) and (140 +/- 48) ug/L,
      respectively, whereas for low virulent strains, the levels of IL-1beta, IL-8, and
      TNF-alpha were (773 +/- 382), (892 +/- 400) and (67 +/- 33) ug/L, respectively.
      CONCLUSIONS: Polysaccharide extracted from Pg could induced the THP-1 cells to
      secrete the cytokines of IL-1beta, IL-8 and TNF-alpha. The level of the cytokines
      produced by the THP-1 cells associates with the bacterial virulent properties.

PMID- 24731419
TI  - [Periodontal tissue in a bio-implant by periodontal ligament cells sheet and bone
      marrow stromal cells sheet].
AB  - OBJECTIVE: To fabricate the bio-implant supported by regenerated periodontal
      tissue utilizing periodontal ligament cells (PDLC)-bone marrow stromal cells
      (BMSC) sheet and natural root. METHODS: Premolars of 2 beagle dogs were extracted
      to prepare the implanted area. Autologous tooth roots were carved into cylinders.
      PDLC and BMSC separated from beagle dogs were cultured into cell sheets in
      medium. Tooth roots were wrapped by one type of cell sheets or both to fabricate
      bio-implant and divided into four groups, tooth roots were wrapped by PDLC sheets
      and BMSC sheets successively (2 samples each dog), tooth roots were wrapped by
      PDLC sheets alone (2 samples each dog), tooth roots were wrapped by BMSC sheet
      alone (2 samples each dog), tooth roots without cell sheet (1 sample each dog).
      The implants were implanted into the mandibles. The mandibles were dissected 12
      weeks later, sliced and stained by HE and Masson dyes for histological
      examination. RESULTS: In the PDLC cell sheet/root implants, histological
      examination revealed that new periodontal-like tissue including cementum,
      periodontium and alveolar bone was regenerated.In the BMSC implants, tooth
      ankylosis was observed. CONCLUSIONS: PDLC sheet and natural root can be used to
      fabricate bio-implant. PDLC sheet could promote periodontal regeneration.

PMID- 24731420
TI  - [Effect of aqueous extracts of Scutellaria baicalensis Georgi and Radix paeoniae
      Alba on the serum IgG1 and IgG2a of the periodontitis mice].
AB  - OBJECTIVE: To examine the effect of aqueous extracts of Scutellaria baicalensis
      Georgi and Radix paeoniae Alba on periodontitis mice and compare the results of
      the two herbs for the treatment of the periodontitis mice. METHODS: Sixty-four
      SPF 12-week-old male Kunming mice were selected and randomly divided into four
      groups:Control group(C); Experimental periodontitis group (P):the peridontitis
      models in Kunming mice were prepared by wrapping silk ligature and inoculating
      with putative periodontopathic bacteria; Scutellaria baicalensis Georgi treatment
      group (SG): periodontitis was induced by the same method described above, the
      mice were gavaged with Scutellaria baicalensis Georgi; Radix paeoniae Alba
      treatment group (RG): periodontitis was induced by the same method described
      above, the mice were gavaged with Radix paeoniae Alba.Four mice were sacrificed
      at each time point of the end of 4, 6, 8 and 10 weeks in each group. The
      histopathological changes of periodontal tissue were observed under microscope
      with HE staining. The level of serum IgG1 and IgG2a was measured by enzyme-linked
      immunosorbent assay (ELISA) . RESULTS: A serious inflammatory response, alveolar
      progressive absorption and a large number of osteoclasts were observed in the
      experimental periodontitis group.However, in SG and RG, the inflammation of the
      periodontal tissue was decreased and tissue repair was significant. The level of
      serum IgG2a in SG (6 week:0.934 +/- 0.006, 8 week:0.743 +/- 0.009, 10 week: 0.674
      +/- 0.008) and RG (6 week: 1.023 +/- 0.032, 8 week: 0.851 +/- 0.032, 10
      week:0.790 +/- 0.009) was significantly decreased after the mice were gavaged
      with the two herbs(P < 0.01). The level of serum IgG2a in SG was significantly
      lower than that of RG (P < 0.01). The level of serum IgG1 in SG (6 week: 0.314 +/
      0.006, 8 week: 0.344 +/- 0.004, 10 week: 0.367 +/- 0.006) and RG (6 week: 0.287
      +/- 0.005, 8 week: 0.303 +/- 0.058, 10 week: 0.336 +/- 0.006) were significantly
      increased (P < 0.01). The level of serum IgG1 in SG was significantly higher than
      that of RG (P < 0.01). CONCLUSIONS: Both the aqueous extracts of Scutellaria
      baicalensis Georgi and Radix paeoniae Alba showed therapeutic effect on
      periodontitis in mice.Scutellaria baicalensis Georgi was more effective than
      Radix paeoniae Alba.

PMID- 24731421
TI  - [Expression of voltage gated sodium channel Nav1.9 in experimental pulpal lesions
      in the rats].
AB  - OBJECTIVE: To investigate the relationship between pulpitis pain and voltage
      gated sodium channel (Nav1.9) by detecting the expression of Nav1.9 at different
      time points of the rat pulpal lesion model. METHODS: Thirty-six SD pulpal lesions
      rat models were divided into three experimental groups, 1 d (n = 12), 3 d (n =
      12) and 5 d group(n = 12).Normal SD rats served as control(n = 12). Tumor
      necrosis factor-alpha (TNF-alpha) and Nav1.9 mRNA expressions were evaluated by
      reverse transcription PCR (RT-PCR) .Nav1.9 protein expressions were analyzed by
      enzyme-linked immunosorbent assay (ELISA) and Western blotting. RESULTS: The
      expression of TNF-alpha in the experimental group (1 d:0.514 +/- 0.098, 3 d:0.739
      +/- 0.104, 5 d:1.238 +/- 0.082) was higher than those in the control group (0.147
      +/- 0.016) (P < 0.01). Nav1.9 mRNA was up-regulated markedly in experimental
      groups (1 d: 0.296 +/- 0.038, 3 d:0.409 +/- 0.013, 5 d: 0.487 +/- 0.028) ,
      compare with control group (0.223 +/- 0.020) (P < 0.05). The ELISA results
      revealed that the level of Nav1.9 in control pulp tissue was (4.013 +/- 0.292)
      ug/L, in painful pulp tissue of 1 d group was (5.143 +/- 0.101) ug/L, in painful
      pulp tissue of 3 d group was (5.835 +/- 0.088) ug/L and in painful pulp tissue of
      5 d group was (6.307 +/- 0.137) ug/L (P < 0.05). Western blotting showed the
      expression of Nav1.9 in experimental groups (1 d: 0.106 +/- 0.007, 3 d:0.170 +/-
      0.013, 5 d:0.238 +/- 0.004) was up-regulated significantly compared with control
      group (0.073 +/- 0.004)(P < 0.05). CONCLUSIONS: The level of Nav1.9 had a
      significant increase in painful pulp tissue. Moreover, with the degree of pain
      aggravation, the expression of Nav1.9 increased in pulp tissue.It suggests that
      Nav1.9 may play an important role in the development of pulpitis pain.

PMID- 24731422
TI  - [Involvement of Smad pathway in proteoglycan 4 expression induced by hydrostatic
      pressure in temporomandibular synovial fibroblasts].
AB  - OBJECTIVE: To examine the expression of proteoglycan 4 (PRG-4) induced by
      hydrostatic pressure in rat temporomandibular synovial fibroblasts and
      investigate the possible mechanism. METHODS: The cultured rat temporomandibular
      synovial fibroblasts were subjected to 100 kPa magnitude intermittent hydrostatic
      pressure (IHP) at frequency of 4 h/day, and the static group served as control.
      The expressions of Smad pathway proteins and p38MAPK pathway proteins were
      analyzed by Western blot and immunofluorescence staining. Then the cells were
      incubated with SB431542, the inhibitor of transforming growth factor (TGF)-beta
      receptor. Western blot and reverse transcription PCR were used to detect the PRG
      4 expression after 72 h. RESULTS: The expression of phosphorylated Smad-2 and
      phosphorylated Smad-3 were increased after 1 h of IHP, reaching a maximum after 2
      h and 4 h of IHP, respectively.However, the protein content of phosphorylated p38
      did not vary significantly. In addition, IHP induced nuclear translocation of
      Smad-2/-3, and the immunofluorescence staining signal intensity markedly
      increased (24.11 +/- 4.70)(P < 0.05). The levels of PRG-4 mRNA were significantly
      increased by IHP (1.48 +/- 0.08)(P < 0.05). Treatment of cells with SB431542
      could decrease the expression of PRG-4 mRNA significantly after IHP (0.47 +/-
      0.05)(P < 0.05). In addition, SB431542 inhibited the expression of PRG-4 protein
      induced by IHP. CONCLUSIONS: Smad signal acts as an essential signal pathway to
      regulate PRG-4 expression induced by IHP.

PMID- 24731423
TI  - [Effect of rat endothelial progenitor cell on proliferation and apoptosis of bone
      marrow mesenchymal stem cell].
AB  - OBJECTIVE: To investigate the effect of endothelial progenitor cell (EPC) on
      regulating proliferation and apoptosis of bone marrow mesenchymal stem cell
      (BMSC) in the indirect co-culture system. METHODS: BMSC and EPC were cultivated
      and identified in vitro.Using transwell inserts to establish EPC and BMSC
      indirect co-culture system.Experimental groups were prepared as follows: BMSC/EPC
      indirect co-culture: BMSC were co-cultured with EPC that were separated in
      transwell insert. CONTROL: BMSC/BMSC were indirect co-cultured at the same cell
      counts with the experimental groups. Colony forming unit-fibroblast(CFU-F) assay
      was studied with three types of EPC/BMSC ratios (1: 1, 10: 1, 100: 1) to assess
      the capacity and efficiency for cell self-renewal.In addition, flow cytometry
      technique was used to detect the cell cycle at co-cultured 3 days and the cell
      apoptosis at co-cultured 3, 7, 10 d. RESULTS: Under indirect co-culture
      condition,EPC could significantly promote cell cycle progress and enhance
      capacity of cell self-renewal. Co-cultured EPC resulted in an accumulation of
      BMSC at S phase [experimental group: (15.72 +/- 2.93)%, control group: (2.02 +/-
      0.66)%, P < 0.01]. CFU-F assay showed that the self-renewal capacity of EPC:
      BMSC/10: 1 group [(50.98 +/- 6.32)%] and 100:1 group[(57.87 +/- 14.06)%] were
      significantly higher than that in control group [(33.07 +/- 9.60)% and (30.06 +/-
      7.20)%](P < 0.01). However,EPC had a slight but non-significant down-regulated
      effect on BMSC apoptosis(P > 0.05). CONCLUSIONS: Under indirect co-culture
      condition, EPC could enhance the proliferation of BMSC, but could not regulate
      cell apoptosis in vitro.

PMID- 24731424
TI  - [Color stability of ceromer veneers/resin cements after accelerated ageing].
AB  - OBJECTIVE: To investigate the color stability of ceromer veneers/resin cements
      after accelerated ageing, and to provide the reference for clinical application
      and choice. METHODS: Fifteen groups of ceromer veneers/resin cements samples,
      five samples in each group, were prepared as experimental groups.In the fifteen
      groups, ceromer veneers in three thickness (1.00, 0.75, 0.50 mm) and resin
      cements of five shades(A1,A3, B 0.5, WO, TR), were matched through permutation
      and combination. Three groups of ceromer veneers with different thickness (1.00,
      0.75, 0.50 mm) were used as control groups. All samples were put into xenon lamp
      ageing instrument to accelerate ageing.Spectrophotometer were used to measure the
      lightness(L(*)), red green color(a(*)) and blue yellow color(b(*)) of samples
      before and after accelerated ageing process, and the change of lightness (DeltaL)
      , red green color (Deltaa) , blue yellow color (Deltab) and color
      variation(DeltaE) were calculated.We investigated the effect of thickness of
      ceromer veneer and color of resin cement on color variation by using analysis of
      variance. RESULTS: The thickness factor and color factor showed significant
      effect on DeltaE values, and they have interaction (P < 0.05). The DeltaE values
      of all experimental groups were lower than 3.3. After accelerated ageing, all
      L(*) values of experimental groups decreased, and DeltaL values were lower than
      2.0. CONCLUSIONS: The thickness of ceromer veneer and the color of resin cement
      could both affect the color stability of ceromer veneers/resin cements. The
      changes of lightness and color in ceromer veneers/resin cements were considered
      clinically acceptable after accelerated ageing.

PMID- 24731425
TI  - [Computer aided design method of digital individual guide for brachytherapy].

PMID- 24731426
TI  - [The surgical treatment of mandibular angle and lateral body fractures and
      application of tension band].

PMID- 24731427
TI  - [Fixation system and bone biomaterial in maxillofacial region].

PMID- 24731428
TI  - [The hypotheses of bisphosphonate-associated osteonecrosis of the jaw].

PMID- 24731429
TI  - [Report of a first mandibular molar with four mesial root canals].

PMID- 24731430
TI  - Influence of antimicrobial regimen on decreased in-hospital mortality of patients
      with MRSA bacteremia.
AB  - Methicillin-resistant Staphylococcus aureus (MRSA) is one of the most important
      causes of bacteremia. Recently, several epidemiological and microbiological
      changes have become evident in MRSA infections. The purposes of this study were
      to assess clinical characteristics of patients with MRSA bacteremia and
      microbiological changes in MRSA. We conducted a retrospective observational study
      on patients with MRSA bacteremia who were hospitalized between 2008 and 2011. We
      used univariate and multivariate analysis to evaluate the predictors associated
      with 30-day mortality. The 7-day and 30-day mortality rates were 12.0% and 25.3%,
      respectively. According to multivariate analysis, the independent predictors that
      associated with 30-day mortality were leukopenia, low serum albumin, high
      sequential organ failure assessment (SOFA) score, and quinolone use within 30
      days. Compared to previous data (2003-2007), the SOFA score of the new data set
      remained unchanged, but in-hospital mortality decreased significantly. In
      particular, the mortality associated with use of vancomycin (VCM) was
      significantly lower. Although the minimum inhibitory concentration of VCM
      required to inhibit the growth of 90% of organisms (MIC90) had not changed, the
      trough value of VCM changed significantly; a VCM trough value of 10 or greater
      was significantly higher compared to previous data. Of the staphylococcal
      cassette chromosome mec (SCCmec) types, SCCmec II values decreased significantly,
      and SCCmec I and IV values increased significantly. Our results indicate that
      changes in VCM usage might contribute to decreased in-hospital mortality.

PMID- 24731431
TI  - Management of hypertension in stroke.
AB  - Elevated blood pressure is present in more than 60% of patients with acute
      stroke. Moderate to severe hypertension affects stroke outcomes, yet the optimal
      management has been a gray area in the care of such patients. Although new data
      are changing the approach, particularly for hemorrhagic events, significant
      questions remain. This article presents the latest evidence on hypertension in
      the setting of ischemic and hemorrhagic stroke and highlights management
      considerations that are relevant to emergency medicine. 

PMID- 24731432
TI  - What are the most clinically useful cutoffs for the Alvarado and Pediatric
      Appendicitis Scores? A systematic review.
AB  - STUDY OBJECTIVE: The objective of this study is to systematically review the
      accuracy of the Alvarado score and Pediatric Appendicitis Score and to identify
      optimal cutoffs for low- and high-risk populations. METHODS: We performed a
      systematic review of the literature and identified 26 studies of the accuracy of
      the Alvarado score and Pediatric Appendicitis Score. Data were abstracted in
      parallel, and only prospective, cohort studies that avoided verification bias
      were included. We calculated summary likelihood ratios for low-, moderate-, and
      high-risk groups, using all possible cutoffs based on available data, even if not
      reported in the original study. RESULTS: The pretest probability of appendicitis
      was approximately 33% in studies of children and approximately 66% in studies of
      adults. Likelihood ratios at different cutoffs for the Alvarado score in adults
      were as follows: 0.03 (<4 points), 0.42 (4 to 6 points), and 3.4 (>= 7 points);
      and 0.01 (<5 points), 0.98 (5 to 8 points), and 6.7 (>= 9 points). Likelihood
      ratios for the Alvarado score in children were as follows: 0.02 (<4 points), 0.27
      (4 to 6 points), and 4.2 (>= 7 points); and 0.04 (<5 points), 1.2 (5 to 8
      points), and 8.5 (>= 9 points). For the Pediatric Appendicitis Score, likelihood
      ratios were 0.13 (<4 points), 0.70 (4 to 7 points), and 8.1 (>= 8 points).
      CONCLUSION: For children with a pretest probability of acute appendicitis of 60%
      or less, an Alvarado score below 4 rules out the diagnosis; this is also true for
      a score less than 5 if the pretest probability is up to approximately 40%. In
      adults with a pretest probability greater than or equal to 60%, an Alvarado score
      of 8 or higher rules in the diagnosis, whereas one of 9 or higher rules in the
      diagnosis at pretest probabilities greater than or equal to 40%. The Pediatric
      Appendicitis Score did not identify clinically useful low- or high-risk groups at
      typical pretest probabilities.

PMID- 24731433
TI  - Using cognitive theory to facilitate medical education.
AB  - BACKGROUND: Educators continue to search for better strategies for medical
      education. Although the unifying theme of reforms was "increasing interest in,
      attention to, and understanding of the knowledge base structures", it is
      difficult to achieve all these aspects via a single type of instruction. METHODS:
      We used related key words to search in Google Scholar and Pubmed. Related search
      results on this topic were selected for discussion. RESULTS: Despite the range of
      different methods used in medical education, students are still required to
      memorize much of what they are taught, especially for the basic sciences.
      Subjects like anatomy and pathology carry a high intrinsic cognitive load mainly
      because of the large volume of information that must be retained. For these
      subjects, decreasing cognitive load is not feasible and memorizing appears to be
      the only strategy, yet the cognitive load makes learning a challenge for many
      students. Cognitive load is further increased when inappropriate use of
      educational methods occurs, e.g., in problem based learning which demands
      clinical reasoning, a high level and complex cognitive skill. It is widely known
      that experts are more skilled at clinical reasoning than novices because of their
      accumulated experiences. These experiences are based on the formation of
      cognitive schemata. In this paper we describe the use of cognitive schemata,
      developed by experts as worked examples to facilitate medical students' learning
      and to promote their clinical reasoning. CONCLUSION: We suggest that cognitive
      load theory can provide a useful framework for understanding the challenges and
      successes associated with education of medical professionals.

PMID- 24731435
TI  - Announcing the winner of the John J. Sciarra IJGO Prize Paper Award for 2013.

PMID- 24731434
TI  - A two-site pilot randomized 3 day trial of high dose left prefrontal repetitive
      transcranial magnetic stimulation (rTMS) for suicidal inpatients.
AB  - BACKGROUND: Suicide attempts and completed suicides are common, yet there are no
      proven acute medication or device treatments for treating a suicidal crisis.
      Repeated daily left prefrontal repetitive transcranial magnetic stimulation
      (rTMS) for 4-6 weeks is a new FDA-approved treatment for acute depression. Some
      open-label rTMS studies have found rapid reductions in suicidality. DESIGN: This
      study tests whether a high dose of rTMS to suicidal inpatients is feasible and
      safe, and also whether this higher dosing might rapidly improve suicidal
      thinking. This prospective, 2-site, randomized, active sham-controlled (1:1
      randomization) design incorporated 9 sessions of rTMS over 3 days as adjunctive
      to usual inpatient suicidality treatment. The setting was two inpatient military
      hospital wards (one VA, the other DOD). PATIENTS: Research staff screened
      approximately 377 inpatients, yielding 41 adults admitted for suicidal crisis.
      Because of the funding source, all patients also had either post-traumatic stress
      disorder, mild traumatic brain injury, or both. TMS METHODS: Repetitive TMS
      (rTMS) was delivered to the left prefrontal cortex with a figure-eight solid core
      coil at 120% motor threshold, 10 Hertz (Hz), 5 second (s) train duration, 10 s
      intertrain interval for 30 minutes (6000 pulses) 3 times daily for 3 days (total
      9 sessions; 54,000 stimuli). Sham rTMS used a similar coil that contained a metal
      insert blocking the magnetic field and utilized electrodes on the scalp, which
      delivered a matched somatosensory sensation. MAIN OUTCOME MEASURE: Primary
      outcomes were the daily change in severity of suicidal thinking as measured by
      the Beck Scale of Suicidal Ideation (SSI) administered at baseline and then
      daily, as well as subjective visual analog scale measures before and after each
      TMS session. Mixed model repeated measures (MMRM) analysis was performed on
      modified intent to treat (mITT) and completer populations. RESULTS: This intense
      schedule of rTMS with suicidal inpatients was feasible and safe. Minimal side
      effects occurred, none differing by arm, and the 3-day retention rate was 88%. No
      one died of suicide within the 6 month followup. From the mITT analyses, SSI
      scores declined rapidly over the 3 days for both groups (sham change -15.3
      points, active change -15.4 points), with a trend for more rapid decline on the
      first day with active rTMS (sham change -6.4 points, active -10.7 points, P =
      0.12). This decline was more pronounced in the completers subgroup [sham change 
      5.9 (95% CI: -10.1, -1.7), active -13 points (95% CI: -18.7, -7.4); P = 0.054].
      Subjective ratings of 'being bothered by thoughts of suicide' declined non
      significantly more with active rTMS than with sham at the end of 9 sessions of
      treatment in the mITT analysis [sham change -31.9 (95% CI: -41.7, -22.0), active
      change -42.5 (95% CI: -53.8, -31.2); P = 0.17]. There was a significant decrease
      in the completers sample [sham change -24.9 (95% CI: -34.4, -15.3), active change
      -43.8 (95% CI: -57.2, -30.3); P = 0.028]. CONCLUSIONS: Delivering high doses of
      left prefrontal rTMS over three days (54,000 stimuli) to suicidal inpatients is
      possible and safe, with few side effects and no worsening of suicidal thinking.
      The suggestions of a rapid anti-suicide effect (day 1 SSI data, Visual Analogue
      Scale data over the 3 days) need to be tested for replication in a larger sample.
      TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01212848, TMS for suicidal
      ideation.

PMID- 24731436
TI  - Contraceptive use among HIV-positive women in Enugu, southeast Nigeria.
AB  - OBJECTIVE: To determine the prevalence and pattern of, and factors associated
      with, contraceptive usage among HIV-positive women in Enugu, southeastern
      Nigeria. METHODS: In a questionnaire-based cross-sectional study, 400 consecutive
      HIV-positive, sexually active women receiving care at the adult HIV clinics of 2
      tertiary health institutions in Enugu were interviewed using pre-tested
      questionnaires between March and August 2012. Descriptive and inferential
      statistical analysis was carried out via Epi Info. RESULTS: The rate of
      contraceptive use was 73.1%; 26.9% (n=91) of women were not using modern
      contraceptives. Male condoms were the most frequent contraception used (78.1%,
      n=193), but 48.2% of women reported inconsistent use. The proportion of women
      using a dual-contraceptive method was 25.1%; none used the female condom. Having
      a regular sexual partner was significantly associated with use of modern
      contraception (odds ratio, 73.00; 95% confidence interval, 34.13-156.13;
      P<0.001). Misconception and fear of adverse effects were the most common reasons
      for not using contraception. CONCLUSION: A considerable proportion of HIV
      positive women in Enugu who did not desire to achieve pregnancy in the following
      2 years (26.9%) had an unmet need for contraception. The use of contraception
      prevents unintended pregnancy and subsequent mother-to-child transmission of HIV
      and should be promoted in the region.

PMID- 24731437
TI  - Predicting why women have elective repeat cesarean deliveries and predictors of
      successful vaginal birth after cesarean.
AB  - OBJECTIVE: To compare the characteristics of women who select elective repeat
      cesarean rather than trial of labor after cesarean (TOLAC) for delivery, and to
      determine individual predictors for success and failure within a TOLAC group and
      observe differences in maternal and neonatal morbidity. METHODS: The present
      descriptive, retrospective, observational study was performed in a regional
      obstetric unit in the United Kingdom. Data were collected from the Northern
      Ireland Maternity System database on all women who gave birth between April 2010
      and April 2012, and had a previous cesarean delivery, and statistical analysis
      was performed. RESULTS: In total, 893 patients were included in the study: 385
      underwent TOLAC and 493 underwent elective repeat cesarean. On comparison, women
      in the elective repeat cesarean group had a shorter inter-delivery interval and
      fewer had had a previous vaginal delivery (P<0.005). Predictors for success in
      the TOLAC group included previous vaginal delivery and a longer inter-delivery
      interval (P<0.05). Successful vaginal birth after cesarean (VBAC) did not have
      higher rates of maternal morbidity. CONCLUSION: The majority of patients (56%)
      chose elective repeat cesarean rather than TOLAC, which has long-term
      implications both clinically and financially. A validated prediction model might
      improve patient counseling and identify women with a high likelihood of
      successful VBAC.

PMID- 24731438
TI  - Uterosubvesical fistula as a cause of infertility.

PMID- 24731439
TI  - Prevalence and etiology of menstrual disorders in Lebanese university students.

PMID- 24731440
TI  - Contribution of obstetrics and gynecology societies in West and Central African
      countries to the prevention of unsafe abortion.
AB  - Unsafe abortion is a major public health issue in low-resource countries. In the
      countries of West and Central Africa, abortion-related maternal mortality rates
      are extremely high, the prevalence of modern contraceptive use is very low, and
      the unmet need for family planning is also high. The International Federation of
      Gynecology and Obstetrics (FIGO) Initiative for the Prevention of Unsafe Abortion
      and its Consequences has contributed substantially toward increasing awareness of
      the problem of abortion, bringing abortion-related issues to the attention of the
      professional societies, individual gynecologists and obstetricians, Ministries of
      Health, healthcare providers, and to the community in general. The promotion of
      quality postabortion care including the use of manual vacuum aspiration,
      misoprostol, and postabortion contraception has greatly improved access to
      services; however, there is still a long way to go. 

PMID- 24731441
TI  - Cognitive behavior therapy versus interpersonal psychotherapy for social anxiety
      disorder delivered via smartphone and computer: a randomized controlled trial.
AB  - In this study, a previously evaluated guided Internet-based cognitive behavior
      therapy for social anxiety disorder (SAD) was adapted for mobile phone
      administration (mCBT). The treatment was compared with a guided self-help
      treatment based on interpersonal psychotherapy (mIPT). The treatment platform
      could be accessed through smartphones, tablet computers, and standard computers.
      A total of 52 participants were diagnosed with SAD and randomized to either mCBT
      (n=27) or mIPT (n=25). Measures were collected at pre-treatment, during the
      treatment, post-treatment and 3-month follow-up. On the primary outcome measure,
      the Liebowitz Social Anxiety Scale - self-rated, both groups showed statistically
      significant improvements. However, mCBT performed significantly better than mIPT
      (between group Cohen's d=0.64 in favor of mCBT). A larger proportion of the mCBT
      group was classified as responders at post-treatment (55.6% versus 8.0% in the
      mIPT group). We conclude that CBT for SAD can be delivered using modern
      information technology. IPT delivered as a guided self-help treatment may be less
      effective in this format. 

PMID- 24731442
TI  - Translation and validation of the Chinese version of the Quality OF Life
      Radiation Therapy Instrument and the Head & Neck Module (QOL-RTI/H&N).
AB  - BACKGROUND: To translate and validate the Chinese version of the Quality Of Life
      Radiation Therapy Instrument and the Head & Neck Module (QOL-RTI/H&N), a disease
      specific scale to measure quality of life (QOL) for patients with head and neck
      cancer (HNC) who received radiotherapy. METHODS: The QOL-RTI/H&N was translated
      and validated according to the standard process: a translation and back
      translation procedure, pilot testing and a validation study. HNC patients were
      enrolled from the Cancer Center of Sun Yat-sen University and assessed using the
      QOL-RTI/H&N, QLQ-C30 and QLQ-H&N35. Reliability (internal consistency
      reliability, split-half reliability and test-retest reliability), validity
      (content validity, construct validity, criterion validity and discriminant
      validity), and responsiveness analysis were performed to evaluate the
      psychometric characteristics of the QOL-RTI/H&N. RESULTS: A total of 238 patients
      (99.2%) completed the questionnaire. Item RTI23 had 16.0% missing data. Other
      items had low percentages of missing data (0.4% or 0.8%) or no missing data. The
      average time to finish the scale was 9.8 minutes. Cronbach's alpha of the domains
      ranged from 0.41 to 0.77. The split-half reliability coefficients ranged from
      0.43 to 0.77. All of the intra-class correlation coefficients were equal to or
      greater than 0.8. All of the item-own domain correlation coefficients were
      greater than those of the item-other domain. Confirmatory factor analysis showed
      that Comparative Fit Index, Normed Fit Index and Non-Normed Fit Index were equal
      to 1.00. Root Mean Square Error of Approximation was 0.01, with 90% CI (0.00,
      0.10). The domain scores of the QOL-RTI/H&N were significantly correlated with
      those of the QLQ-C30 or QLQ-H&N3. All domain scores of patients in different
      radiotherapy stages were statistically significant (P < 0.05), apart from the
      speech domain. CONCLUSIONS: The Chinese version of the QOL-RTI/H&N is a valid,
      reliable and responsive scale to measure QOL in HNC patients and can be used to
      assess the effects of radiotherapy treatment on these patients.

PMID- 24731443
TI  - Hepcidin and sports anemia.
AB  - Iron is an important mineral element used by the body in a variety of metabolic
      and physiologic processes. These processes are highly active when the body is
      undergoing physical exercises. Prevalence of exercise-induced iron deficiency
      anemia (also known as sports anemia) is notably high in athletic populations,
      particularly those with heavy training loads. The pathogenesis of sports anemia
      is closely related to disorders of iron metabolism, and a more comprehensive
      understanding of the mechanism of iron metabolism in the course of physical
      exercises could expand ways of treatment and prevention of sports anemia. In
      recent years, there have been remarkable research advances regarding the
      molecular mechanisms underlying changes of iron metabolism in response to
      physical exercises. This review has covered these advances, including effects of
      exercise on duodenum iron absorption, serum iron status, iron distribution in
      organs, erythropoiesis, and hepcidin's function and its regulation. New methods
      for the treatment of exercise-induced iron deficiency are also discussed. 

PMID- 24731444
TI  - Endothelin-1 activation of the endothelin B receptor modulates pulmonary
      endothelial CX3CL1 and contributes to pulmonary angiogenesis in experimental
      hepatopulmonary syndrome.
AB  - Hepatic production and release of endothelin-1 (ET-1) binding to endothelin B
      (ETB) receptors, overexpressed in the lung microvasculature, is associated with
      accumulation of pro-angiogenic monocytes and vascular remodeling in experimental
      hepatopulmonary syndrome (HPS) after common bile duct ligation (CBDL). We have
      recently found that lung vascular monocyte adhesion and angiogenesis in HPS
      involve interaction of endothelial C-X3-C motif ligand 1 (CX3CL1) with monocyte
      CX3C chemokine receptor 1 (CX3CR1), although whether ET-1/ETB receptor activation
      influences these events is unknown. Our aim was to define if ET-1/ETB receptor
      activation modulates CX3CL1/CX3CR1 signaling and lung angiogenesis in
      experimental HPS. A selective ETB receptor antagonist, BQ788, was given for 2
      weeks to 1-week CBDL rats. ET-1 (+/-BQ788) was given to cultured rat pulmonary
      microvascular endothelial cells overexpressing ETB receptors. BQ788 treatment
      significantly decreased lung angiogenesis, monocyte accumulation, and CX3CL1
      levels after CBDL. ET-1 treatment significantly induced CX3CL1 production in lung
      microvascular endothelial cells, which was blocked by inhibitors of Ca(2+) and
      mitogen-activated protein kinase (MEK)/ERK pathways. ET-1-induced ERK activation
      was Ca(2+) independent. ET-1 administration also increased endothelial tube
      formation in vitro, which was inhibited by BQ788 or by blocking Ca(2+) and
      MEK/ERK activation. CX3CR1 neutralizing antibody partially inhibited ET-1 effects
      on tube formation. These findings identify a novel mechanistic interaction
      between the ET-1/ETB receptor axis and CX3CL1/CX3CR1 in mediating pulmonary
      angiogenesis and vascular monocyte accumulation in experimental HPS.

PMID- 24731445
TI  - Glucose specifically regulates TRPC6 expression in the podocyte in an AngII
      dependent manner.
AB  - Slit diaphragm and podocyte damage is crucial in the pathogenesis of proteinuria
      in diabetic nephropathy (DNP). Gain-of-function mutations in TRPC6, a slit
      diaphragm-associated ion channel, cause glomerulosclerosis; TRPC6 expression is
      increased in acquired glomerular disease. Hyperglycemia and high intrarenal
      angiotensin II (AngII) levels could contribute to podocyte injury in DNP. We
      determined whether glucose regulates TRPC6 expression and TRPC6-mediated Ca(2+)
      influx into the podocyte and whether these effects are AngII dependent. High
      glucose levels increased TRPC6 mRNA and protein expression in cultured podocytes;
      however, TRPC1 and TRPC5 mRNA expression was unaltered. AngII and inducing
      podocyte injury also specifically increased TRPC6 expression. Angiotensin
      receptor blockade and inhibition of local AngII production through angiotensin
      converting enzyme inhibition prevented glucose-mediated increased TRPC6
      expression. In addition, high glucose concentration pretreatment enhanced Ca(2+)
      influx in podocytes, which was prevented by concomitant angiotensin receptor
      blockade application and TRPC6 knockdown. Studies with a TRPC6 luciferase
      promoter construct demonstrated a glucose concentration-dependent effect on TRPC6
      promoter activity. In vivo, podocyte TRPC6 protein expression was increased in
      proteinuric streptozotocin-induced diabetic rats. These data suggest that glucose
      can activate a local renin-angiotensin system in the podocyte, leading to
      increased TRPC6 expression, which enhances TRPC6-mediated Ca(2+) influx.
      Regulation of TRPC6 expression could be an important factor in podocyte injury
      due to chronic hyperglycemia and the antiproteinuric effect of angiotensin
      receptor blockade or angiotensin-converting enzyme inhibition in DNP.

PMID- 24731446
TI  - Inducing a visceral organ to protect a peripheral capillary bed: stabilizing
      hepatic HIF-1alpha prevents oxygen-induced retinopathy.
AB  - Activation of hypoxia-inducible factor (HIF) can prevent oxygen-induced
      retinopathy in rodents. Here we demonstrate that dimethyloxaloylglycine (DMOG)
      induced retinovascular protection is dependent on hepatic HIF-1 because mice
      deficient in liver-specific HIF-1alpha experience hyperoxia-induced damage even
      with DMOG treatment, whereas DMOG-treated wild-type mice have 50% less avascular
      retina (P < 0.0001). Hepatic HIF stabilization protects retinal function because
      DMOG normalizes the b-wave on electroretinography in wild-type mice. The
      localization of DMOG action to the liver is further supported by evidence that i)
      mRNA and protein erythropoietin levels within liver and serum increased in DMOG
      treated wild-type animals but are reduced by 60% in liver-specific HIF-1alpha
      knockout mice treated with DMOG, ii) triple-positive (Sca1/cKit/VEGFR2), bone
      marrow-derived endothelial precursor cells increased twofold in DMOG-treated wild
      type mice (P < 0.001) but are unchanged in hepatic HIF-1alpha knockout mice in
      response to DMOG, and iii) hepatic luminescence in the luciferase oxygen
      dependent degradation domain mouse was induced by subcutaneous and
      intraperitoneal DMOG. These findings uncover a novel endocrine mechanism for
      retinovascular protection. Activating HIF in visceral organs such as the liver
      may be a simple strategy to protect capillary beds in the retina and in other
      peripheral tissues.

PMID- 24731447
TI  - LOX-1 is a novel therapeutic target in neonatal hypoxic-ischemic encephalopathy.
AB  - Neonatal hypoxic-ischemic encephalopathy (HIE) remains a serious burden in
      neonatal care. Hypothermia provides a good outcome in some babies with HIE. Here,
      we investigated the biological mechanisms of its neuroprotective effect and
      sought for a new therapeutic target. We made neonatal HIE rats and subjected some
      of them to hypothermia at 28 degrees C for 3 hours. We pathologically confirmed
      the efficacy of hypothermia against the neonatal HIE brain. To clarify the
      molecular mechanism of hypothermia's efficacy, we analyzed mRNA expression,
      immunoassay, and pathology in the brain with or without HIE and/or hypothermia.
      We selected from these analyses 12 molecules with possible neuroprotective
      effects. After identification of lectin-like oxidized low-density lipoprotein
      receptor-1 (LOX-1) as a therapeutic target candidate, we examined the efficacy of
      an anti-LOX-1 neutralizing antibody in neonatal HIE rats. Administration of an
      anti-LOX-1 neutralizing antibody reduced infarction area, brain edema, and
      apoptotic cell death to a degree comparable with hypothermia. Protection from
      those pathological conditions was considered part of the therapeutic mechanism of
      hypothermia. The efficacy of administering anti-LOX-1 neutralizing antibody was
      similar to that of hypothermia. LOX-1 is a promising therapeutic target in
      neonatal HIE, and the inhibition of LOX-1 may become a novel treatment for babies
      who have experienced asphyxia. 

PMID- 24731449
TI  - Extended negative pressure wound therapy-assisted dermatotraction for the closure
      of large open fasciotomy wounds in necrotizing fasciitis patients.
AB  - BACKGROUND: Necrotizing fasciitis (NF) is a rapid progressive infection of the
      subcutaneous tissue or fascia and may result in large open wounds. The surgical
      options to cover these wounds are often limited by the patient condition and
      result in suboptimal functional and cosmetic wound coverage. Dermatotraction can
      restore the function and appearance of the fasciotomy wound and is less invasive
      in patients with comorbidities. However, dermatotraction for scarred, stiff NF
      fasciotomy wounds is often ineffective, resulting in skin necrosis. The authors
      use extended negative pressure wound therapy (NPWT) as an assist in
      dermatotraction to close open NF fasciotomy wounds. The authors present the
      clinical results, followed by a discussion of the clinical basis of extended NPWT
      assisted dermatotraction. METHODS: A retrospective case series of eight patients
      with NF who underwent open fasciotomy was approved for the study. After serial
      wound preparation, dermatotraction was applied in a shoelace manner using elastic
      vessel loops. Next, the extended NPWT was applied over the wound. The sponge was
      three times wider than the wound width, and the transparent covering drape almost
      encircled the anatomical wound area. The negative pressure of the NPWT was set at
      a continuous 100 mmHg by suction barometer. The clinical outcome was assessed
      based on wound area reduction after treatment and by the achievement of direct
      wound closure. RESULTS: After the first set of extended NPWT-assisted
      dermatotraction procedures, the mean wound area was significantly decreased
      (658.12 cm(2) to 29.37 cm(2); p = 0.002), as five out of eight patients achieved
      direct wound closure. One patient with a chest wall defect underwent latissimus
      dorsi musculocutaneous flap coverage, with primary closure of the donor site. Two
      Fournier's gangrene patients underwent multiple sets of treatment and finally
      achieved secondary wound closure with skin grafts. The patients were followed up
      for 18.3 months on average and showed satisfactory results without wound
      recurrence. CONCLUSIONS: Extended NPWT-assisted dermatotraction advances scarred,
      stiff fasciotomy wound margins synergistically in NF and allows direct closure of
      the wound without complications. This method can be another good treatment option
      for the NF patient with large open wounds whose general condition is unsuitable
      for extensive reconstructive surgery.

PMID- 24731450
TI  - Geophagy practices and the content of chemical elements in the soil eaten by
      pregnant women in artisanal and small scale gold mining communities in Tanzania.
AB  - BACKGROUND: Geophagy, a form of pica, is the deliberate consumption of soil and
      is relatively common across Sub-Saharan Africa. In Tanzania, pregnant women
      commonly eat soil sticks sold in the market (pemba), soil from walls of houses,
      termite mounds, and ground soil (kichuguu). The present study examined geophagy
      practices of pregnant women in a gold mining area of Geita District in
      northwestern Tanzania, and also examined the potential for exposure to chemical
      elements by testing soil samples. METHOD: We conducted a cross sectional study
      using a convenience sample of 340 pregnant women, ranging in age from 15-49
      years, who attended six government antenatal clinics in the Geita District,
      Tanzania. Structured interviews were conducted in June-August, 2012, to
      understand geophagy practices. In addition, soil samples taken from sources
      identified by pregnant women practicing geophagy were analysed for mineral
      element content. RESULTS: Geophagy was reported by 155 (45.6%) pregnant women
      with 85 (54.8%) initiating the practice in the first trimester. A total of 101
      (65%) pregnant women reported eating soil 2 to 3 times per day while 20 (13%) ate
      soil more than 3 times per day. Of 155 pregnant women 107 (69%) bought pemba from
      local shops, while 48 (31%) consumed ground soil kichuguu. The estimated mean
      quantity of soil consumed from pemba was 62.5 grams/day. Arsenic, chromium,
      copper, iron, manganese, nickel and zinc levels were found in both pemba and
      kichuguu samples. Cadmium and mercury were found only in the kichuguu samples.
      Based on daily intake estimates, arsenic, copper and manganese for kichuguu and
      copper and manganese for pemba samples exceed the oral Minimum Risk Levels
      designated by the U.S. Agency for Toxic Substance and Disease Registry.
      CONCLUSION: Almost 50% of participants practiced geophagy in Geita District
      consistent with other reports from Africa. Both pemba and kichuguu contained
      chemical elements at varying concentration, mostly above MRLs. As such, pregnant
      women who eat soil in Geita District are exposed to potentially high levels of
      chemical elements, depending upon frequency of consumption, daily amount consumed
      and the source location of soil eaten.

PMID- 24731451
TI  - Physical activity, functional capacity, and step variability during walking in
      people with lower-limb amputation.
AB  - Physical activity is important for general health. For an individual with
      amputation to sustain physical activity, certain functional capacity might be
      needed. Gait variability is related to the incidence of falls. This study
      explored the relationship between physical activity and a few common performance
      measures (six-minute walk test, step length variability, step width variability,
      and comfortable walking speed) in individuals with unilateral lower-limb
      amputation. Twenty individuals completed the study (age: 50+/-11yrs). Twelve of
      them had transtibial amputation, seven had transfemoral amputation, and one had
      through-knee amputation. Gait data was collected by the GaitRite instrumented
      walkway while participants performed a 3-min comfortable walking trial followed
      by a six-minute walk test. Physical activity was indicated by the mean of 7-day
      step counts via a pedometer. Gait variability was calculated by the coefficient
      of variation. Pearson correlation analysis was conducted between physical
      activity level and the 4 performance measures. Significance level was set at
      0.05. Physical activity correlates strongly to comfortable walking speed
      (r=0.76), six-minute walk distance (r=0.67), and correlates fairly to step width
      variability (r=0.44). On the contrary, physical activity is inversely related to
      step length variability of the prosthetic leg (r=-0.46) and of the sound leg (r=
      0.47). Having better functional capacity and lateral stability might enable an
      individual with lower-limb amputation to engage in a higher physical activity
      level, or vise versa. However, our conclusions are only preliminary as limited by
      the small sample size. 

PMID- 24731448
TI  - STAT4 knockout mice are more susceptible to concanavalin A-induced T-cell
      hepatitis.
AB  - STAT4, which is activated mainly by IL-12, promotes inflammatory responses by
      inducing Th1 and Th2 cytokines. Recent genome-wide association studies indicate
      that STAT4 gene variants are associated with risk of various types of liver
      diseases, but how STAT4 contributes to liver disease pathogenesis remains
      obscure. In this study, STAT4 activation was detected in liver immune cells from
      patients with viral hepatitis and autoimmune hepatitis, as well as in a mouse
      model of concanavalin A (Con A)-induced hepatitis. Such STAT4 activation was
      detected mainly in T cells, natural killer T cells, and macrophages and Kupffer
      cells, and was diminished in Il12a(-/-) and Il12b(-/-) mice. As expected,
      disruption of the Stat4 gene reduced production of Th1 and Th2 cytokines, but
      surprisingly exacerbated Con A-induced liver injury. Similarly, disruption of
      Il12a or Il12b also augmented Con A-induced hepatocellular damage. Further
      studies showed that hepatic natural killer T (NKT) cells from Con A-treated
      Stat4(-/-) mice had higher levels of FasL expression and increased cytotoxicity
      against hepatocytes than those from Con A-treated WT mice. In vitro, blocking
      FasL attenuated Stat4(-/-) NKT cytotoxicity against hepatocytes. In conclusion,
      despite up-regulation of proinflammatory cytokines, STAT4 protects against acute
      T-cell hepatitis, which is mediated by direct or indirect down-regulation of FasL
      expression on NKT cells.

PMID- 24731452
TI  - [How to standardize the clinical and basic research of magnetic resonance].

PMID- 24731453
TI  - [T2-SPACE MRI for the ocular motor nerves in the brainstem of normal controls].
AB  - OBJECTIVE: To study the detail functional anatomy of ocular motor nerves in the
      brainstem by high-resolution magnetic resonance imaging (MRI). METHODS: Sixty
      eight normal subjects with high resolution MRI were recruited in our study. The
      ocular motor nerves at the brainstem were performed using 3-dimensional, T(2)
      weighted Turbo-Spin-Echo sequence with high sampling efficiency sequence (3D T(2)
      SPACE), Parameters: TR = 1000 ms, TE = 134 ms, averages = 2, thickness = 0.8 mm,
      FOV = 225 mm*225 mm, matrix = 384*384, total scanning time is 4 min 2 s. Nerves
      in the brainstem were observed in oblique axial, oblique sagittal and coronal
      planes acquired with multi-planar reformation (MPR). The diameters of oculomotor
      nerves (CN3) and abducens (CN6) in the brainstem were measured in 68 normal
      subjects on MR images by 2 neuro-radiologists. RESULTS: All of 136 CN3 and CN6 of
      the cisternal segment were well demonstrable in 68 normal subjects (100%).
      Trochlear nerves (CN4) were depicted 87%. The diameters of CN3 and CN6 in the
      cistern were 2.2 mm, 1.3 mm, had no linear correlation with age. There were no
      significant difference between the results of the 2 radiologist (F = 2.557,
      1.329, P = 0.085, 0.271). CONCLUSIONS: T(2)-SPACE sequence combined with MPR
      could precisely show the ocular motor nerves, as well as the relationship with
      adjacent structures in the cistern. The exact data measurement can provide more
      accurate anatomical basis for some special forms of neuropathic strabismus.

PMID- 24731454
TI  - [Resting-state functional MRI research of the auditory cortex in patients with
      long-term unilateral hearing loss].
AB  - OBJECTIVE: To evaluate functional connectivity in patients with unilateral
      sensorineural hearing loss(USNHL) using resting-state fMRI. METHODS: Functional
      connectivity MRI were employed in 29 patients with SNHL (15 left, 14 right) with
      averaged hearing level above 70 dB HL for the deaf ear, and matched 15 and 14
      normal hearing subjects, respectively, were recruited. Functional connectivity
      mappings between the SNHL patients and normal hearing subjects were evaluated and
      the differences were contrasted. RESULTS: The positive functional connectivity of
      auditory cortex with whole brain in USNHL patients is weaker than that in normal
      subjects both in volume and intensity. Using the affected side AIas a seed, left
      and right Laterality index(LI)of auditory cortex was 30.14, -31.25, respectively.
      Using the healthy side as a seed, the LI of auditory cortex was 0.1, 19.37,
      respectively. Compared to normal subjects, increased activation in bilateral
      precentral gyrus, left middle frontal gyrus, left superior frontal gyrus and
      posterior cingulate cortex/precuneus were found in left USNHL patients.
      Contrasted with normal subjects, no significant difference was found between the
      normal subjects and right SNHL patients, except the right caudate nucleus using
      left AIas a seed. CONCLUSION: The reduced functional connectivity among the
      affected side and healthy side auditory cortex as well as associated auditory
      cortex may suggest a result of functional reorganization adaptive to the SNHL.

PMID- 24731455
TI  - [Evaluation of signal noise ratio on analysis of clear cell renal cell carcinoma
      using DWI with multi-b values].
AB  - OBJECTIVE: To explore the influence of signal noise ratio (SNR) on analysis of
      clear cell renal cell carcinoma (CCRCC) using DWI with multi-b values. METHODS:
      The images of 17 cases with CCRCC were analyzed, including 17 masses and 9 pure
      cysts. The signal intensity of the cysts and masses was measured separately on
      DWI for each b value. The minimal SNR, as the threshold, was recorded when the
      signal curve manifest as the single exponential line. The SNR of the CCRCC was
      calculated on DWI for each b value, and compared with the threshold by
      independent Two-sample t Test. RESULTS: The signal decreased on DWI with
      increased b factors for both pure cysts and CCRCC. The threshold is 1.29 +/-
      0.17, and the signal intensity of the cysts on DWI with multi-b values shown as a
      single exponential line when b <= 800 s/mm(2). For the CCRCC, the SNR is similar
      to the threshold when b = 1 000 s/mm(2) (t = 0.40, P = 0.69), and is lower when b
      = 1 200 s/mm(2) (t = -2.38, P = 0.03). CONCLUSION: The SNR should be sufficient
      for quantitative analysis of DWI, and the maximal b value is 1000 s/mm(2) for
      CCRCC.

PMID- 24731456
TI  - [The value of soft tissue neurogenic tumors in the extremities with 3.0 T
      magnetic resonance imaging].
AB  - OBJECTIVE: To explore the diagnostic value of 3.0T MRI in neurogenic tumor of
      soft tissue in the extremities. METHODS: The MRI appearance of 17 neurogenic
      tumors with pathological confirmation was retrospectively analyzed. Various
      imaging characteristics of tumors were evaluated and different imaging findings
      were compared. The diagnosis value of each MRI features was evaluated with
      receiver-operating-characteristics (ROC) analysis. RESULTS: In the benign tumors
      significant differences between neurilemmoma and neurofibromas were noted for the
      position (P = 0.044). Heterogenicity on T(2)-weighted fat suppression images was
      also significant in differentiating between neurilemmoma and neurofibromas ( P =
      0.020) . The shape of tumors, maximum length of tumor short diameter, edem around
      masses, relationship with adjoining fascia had the best discriminatory ability.
      The ROC analysis yield the area under curve (AUC) of them was 0.967 (P = 0.037),
      0.923 (P = 0.048) , 0.981 (P = 0.034) , 0.981 (P = 0.034), respectively.
      CONCLUSION: If the neurogenic tumors of soft tissue in the extremities had one or
      several features of these characteristics (irregular margin, big volume, edem
      around masses, aggressive behavior with adjoining fascia) on 3.0T MRI, they had
      more possibility to be malignant. T(2)-weighted fat suppression series on 3.0TMRI
      was very important for discrimination of tumor histological characteristics.

PMID- 24731458
TI  - [Effects of telmisartan on IKCa1 potassium channel after T-lymphocyte activation
      and proliferation in peripheral blood of hypertensive patients in Xinjiang
      Kazakh].
AB  - OBJECTIVE: To explore the effects of Telmisartan on IKCa1 potassium channel after
      T-lymphocyte activation and proliferation in peripheral blood of hypertensive
      patients in Xinjiang Kazakh. METHODS: Peripheral blood T cells in vitro culture
      were isolated from 30 Xinjiang Kazakh outpatients without antihypertensive drug
      therapy. They were randomly selected from our hypertension clinic from August
      2012 to December 2012. The proliferated T lymphocytes were divided into control,
      telmisartan and TRAM-34 groups. After culturing for 0, 24, 48 h after
      corresponding treatments, the patch-clamp technique was employed to record the
      electrophysiological changes of IKCa1 potassium channel of T lymphocytes.
      RESULTS: Under different treatment conditions, the IKCa1 potassium channel showed
      different electrophysiological changes. Pairwise comparison was made among the
      groups on the same time. For the telmisartan group, IKCa1 potassium channel peak
      current, peak current density of intervention 24 h and 48 h were significantly
      reduced compared with the control group (24 h:(835 +/- 117)vs(1 471 +/- 255) pA,
      (213 +/- 61) vs (388 +/- 129) pA/pF; 48 h:(631 +/- 142) vs (1 555 +/- 383) pA,
      (155 +/- 54) vs (388 +/- 114) pA/pF, all P < 0.01) . And the blocking rates of 0
      h, 24 h and 48 h of telmisartan on IKCa1 potassium channel were 6.8%, 45.1% and
      60.1% respectively. CONCLUSION: Telmisartan can block the IKCa1 potassium channel
      of T lymphocytes in peripheral blood of hypertensive patients in Xinjiang Kazakh.
      It suggests that telmisartan may play an anti-inflammatory effect by blocking the
      IKCa1 potassium channels of T lymphocyte activation.

PMID- 24731457
TI  - [A MRI study of lumbar plexus in patients with degenerative lumbar scoliosis
      after extreme lateral interbody fusion].
AB  - OBJECTIVE: To analyze the magnetic resonance neural imaging distribution of
      lumbar plexus in patients with degenerative lumbar scoliosis and evaluate its
      value and the safety of extreme lateral interbody fusion (XLIF). METHODS: Three
      dimensional fast imaging employing steady-state acquisition (3D FIESTA) sequences
      of lumbar spine were scanned on 19 patients with degenerative lumbar scoliosis,
      including levo scoliosis (n = 11) and dextro scoliosis (n = 8). All images were
      sent to workstation for multiplanar volume reconstruction to analyze the
      distribution of lumbar plexus from L1-2 to L4-5 level. The axial image distance
      (AID) was measured between anterior edge of lumbar plexus and sagittal central
      perpendicular line (SCPL). SCPL was drawn perpendicularly to the sagittal plane
      of intervertebral disc and passed through its central point. It was actually the
      pathway of guide wire implanting procedure and the ongoing axis of work channel
      during XLIF. With respect to SCPL, the distance with a positive value indicated
      posterior neural tissue whereas a negative value anterior neural tissue. The
      differences of AID were compared between convex and concave sides and among
      different cases and levels. RESULTS: From L1-2 to L4-5 level, the AID on the
      concave side in levo scoliosis or dextro scoliosis cases was (13.7 +/- 2.5) mm/
      (12.9 +/- 5.5) mm, (8.3 +/- 4.7) mm/ (8.5 +/- 5.7) mm, (2.7 +/- 3.6) mm/ (2.5 +/-
      7.2) mm and (-4.2 +/- 3.8) mm/ (-3.8 +/- 7.1) mm respectively. They were located
      significantly posteriorly to the relevant disc compared to those on the convex
      side at the same intervertebral space (P < 0.05). The differences of AID at the
      same side, concave or convex side, was significant (P < 0.05). No significant
      differences of lumbar plexus distribution existed between levo scoliosis and
      dextro scoliosis cases (P > 0.05). CONCLUSION: Lumbar plexus passes through psoas
      posteriorly to SCPL on both side at L1-2, L2-3 level and on the concave side at
      L3-4 level. And they shift anteriorly to SCPL on the convex side at L3-4 level
      and on both sides at L4-5 level. It indicates a ventral migration of lumbar
      plexus from L1-2 to L4-5 level. Preoperative magnetic resonance neural imaging is
      valuable for assessing the safety of XLIF approach. Operation from the concave
      may reduce the risk of injury to lumbar plexus.

PMID- 24731459
TI  - [Correlation between electrocardiogram, myocardial biomarkers and left
      ventricular dysfunction in acute anterior ST segment elevation myocardial
      infarction].
AB  - OBJECTIVE: To analyze the correlation between ST segment elevation, Q wave and
      peak biomarkers with left ventricular dysfunction in patients with acute anterior
      ST elevation myocardial infarction (STEMI). METHODS: A total of 138 consecutive
      inpatients with acute anterior STEMI, left anterior descending branch as the
      convict vessel, from January 2009 to January 2012 in our hospital were enrolled
      in this study. They were divided into reperfusion (n = 92) and non-reperfusion
      group(n = 46). Clinical data, electrocardiogram, peak biomarkers, type B
      natriuretic peptide (BNP) were collected by physicians and the patients were
      followed up three months. RESULTS: The sum of the ST segments elevation, Q waves
      and Q wave leads in anterior STEMI were positive correlation with the Killip
      grades, myocardium biomarkers, BNP and left ventricle end diastolic diameters
      (LVEDD) [gamma, 0.52-0.75, P < 0.01], while negative correlation with left
      ventricle ejection fraction (LVEF) [gamma, -0.63--0.95, P < 0.01]. The sum of R
      wave altitude was negative correlation with myocardium biomarkers, BNP and LVEDD
      in three months after the onset of STEMI [gamma, -0.48--0.79, P < 0.01], while
      positive correlation with LVEF [gamma, 0.73-0.82, P < 0.01]. BNP, one of the best
      markers of left heart dysfunction, was found to be strongly negative correlation
      with LVEF in acute stage and three months after the onset of STEMI [gamma , 
      0.92, -0.80, P < 0.01]. CONCLUSION: There are close correlations between
      electrocardiogram, myocardial biomarkers and left ventricular dysfunction in
      acute anterior ST segment elevation myocardial infarction, which may be strong
      predictors for the short-term prognosis.

PMID- 24731460
TI  - [Outdoor activity and myopia among 681 primary students in urban and rural
      regions of Beijing].
AB  - OBJECTIVE: To explore the association between outdoor activity and myopia among
      681 primary students from Beijing. METHODS: School-based, cross-sectional
      investigation. Eye examination includes the visual acuity test, auto-refractor,
      slit lamp, ocular biometry and non-mydriatic fundus camera. Questionnaire
      includes regular items, near work, outdoor activity and social-economic status.
      RESULTS: The mean time spent outdoors was 1.6 +/- 0.8 hours daily. Time spent on
      outdoor sports and outdoor leisure were 0.7 +/- 0.1 hours daily, 1.0 +/- 0.8
      hours daily, respectively. Mean time of outdoor activity in urban was 1.1 +/- 0.4
      hours daily, compared with 2.2 +/- 0.8 hours daily in rural (P = 0.000). In grade
      1, total time spent outdoors is significantly different between myopia and non
      myopia (1.4 +/- 0.6 vs 1.8 +/- 0.8 hours daily, P = 0.000), similar to outdoor
      leisure (0.8 +/- 0.6 vs 1.1 +/- 0.9 hours daily, P = 0.000). The same trend was
      also found in grade-4. CONCLUSION: The mean time spent outdoors was 1.6 +/- 0.8
      hours daily. Myopia spent a lower outdoor activity compared with non-myopia. More
      outdoor activity, e.g., in schools, may potentially be helpful to reduce the high
      prevalence of myopia in the young generation.

PMID- 24731461
TI  - [CT analysis of dehiscent sigmoid plate presenting as pulsatile tinnitus].
AB  - OBJECTIVE: To evaluate the CT the characteristics of dehiscent sigmoid plate
      accompanied with pulsatile tinnitus (PT). METHODS: Dual phase contrast
      enhancement CT data of 15 PT patients were analyzed retrospectively. RESULTS:
      Dehiscent sigmoid plate was located on the same side of PT in all patients.
      Thirteen defects had been showed in both CT images and surgery. Among of them,
      eight defects located on the descending segment, 3 on the superior curve, and the
      other 2 defects involved the superior curve and descending segment of sigmoid
      sinus simultaneously. The maximum anteroposterior and vertical diameters of
      defect measured in CT images were significant larger than that measured during
      surgery. There were still 5 defects showed in CT images, which did not been found
      during surgery. Among 9 patients with unilateral dominant brain venous systems,
      all the dehiscent sigmoid plates were seen on the dominant side. The other 2
      patients showed co-dominant brain venous systems, whose the dehiscent sigmoid
      plates were on the left side. In addition, extensive pneumatized temporal bone
      filled with air was found in all patients. CONCLUSION: Dehiscent sigmoid plate
      commonly located on the anterior, lateral, or anterolateral wall of the superior
      curve or descending segment of the sigmoid plate, which usually coexist with the
      strong unilateral dominant brain venous system and extensive temporal bone
      pneumatization.

PMID- 24731462
TI  - [Imaging evaluation of the cases with tympanicum and pulsatile tinnitus].
AB  - OBJECTIVE: To analyze the CT and MRI features of glomus tympanicum tumors
      accompanied with tympanitis and evaluate the diagnostic value of CT and MRI in
      order to improve the cognition for the disease. METHODS: The clinical materials
      and images of 8 patients with the symptoms of pulsatile tinnitus and hearing loss
      in whom glomus tympanicum tumors with tympanitis surgically and pathologically
      confirmed were retrospectively reviewed. The characteristics and diagnostic value
      of CT and MR imaging were summarized. RESULTS: By CT examination the lesions in
      middle ear and mastoid were preoperatively diagnosed as tympanitis in five cases
      and only in three cases the glomus tympanicum tumors were suspected. In six
      patients underwent MR examination the lesions were all preoperatively diagnosed
      as glomus tympanicum tumors accompanied with tympanitis. HRCT scanning of the
      temporal bone in all patients showed the soft tissue lesions in the tympanic
      cavity and mastoid, and the caritas tympanic were mostly (n = 3) or completely (n
      = 5) occupied by soft tissue lesions, but the auditory ossicles were all without
      destruction. Contrast-enhanced axial CT scanning performed in five cases showed
      less soft tissue mass on the cochlear promontory, and the size of mass was less
      than that observed in MR imaging. MR T(1)-weighted imaging showed the presence of
      isointense lesions in middle ear and isointense (n = 3) or hyperintense (n = 3)
      lesions in mastoid. On T(2)-weighted imaging the lesions with slight hyperintense
      were viewed in the middle ear and the lesions with hyperintense in mastoid. T(1)
      weighted gadolinium-enhanced MRI showed the masses in tympanum were markedly
      increased enhancement, but the lesions in mastoid without enhancement. MRI and CT
      imaging revealed the masses in six cases of eight extending to the eustachian
      tube. CONCLUSION: When the glomus tympanicum tumor was accompanied with
      tympanitis the tumor could be misdiagnosed or missed only by CT examination. The
      patients with pulsatile tinnitus should be taken seriously. MRI with contrast
      enhancement is superior to CT in the preoperative diagnosis and accurately
      evaluation for the glomus tympanicum tumors with tympanitis.

PMID- 24731463
TI  - [Role and mechanism of NKp44+NK cells in the proliferation and inflammation of
      synovium of rheumatoid arthritis patients].
AB  - OBJECTIVE: To explore the effects of NKp44+NK cells from rheumatoid arthritis
      (RA) patients on the proliferation and monocyte chemotactic protein 1 production
      of fibroblast-like synoviocytes (FLS). METHODS: The proportions of natural killer
      (NK) p44 NK cells in peripheral blood (PB) of 50 RA patients and 50 healthy
      individuals were detected by flow cytometry. Synovial fluid (SF) samples from 30
      RA patients were also detected. NKp44+NK cells in RA SF were sorted by flow
      cytometry for 5 times. The supernatant level of interleukin (IL)-22 was measured
      by enzyme-linked immunosorbent assay (ELISA). The proliferation of FLS after an
      addition of culture supernatant of NKp44+NK cells was detected by methyl
      thiazolyl tetrazolium (MTT) at 24, 48 and 72 h. Monocyte chemotactic protein
      (MCP)-1 production of RA FLS after an addition of rhIL-22 was detected by ELISA.
      RESULTS: The proportion of NKp44+NK cells in PB of RA patients was significantly
      higher than that of normal controls while the proportion of NKp44+NK cells in SF
      of RA patients was higher than that in PB of matched RA patients (1.270% vs 0,
      15.190% vs 2.425%, P < 0.01). The supernatant level of IL-22 in NKp44+NK cell
      culture was (1 603 +/- 332) ng/L. Rapid proliferation of RA FLS was observed at
      24, 48, 72 h after an addition of culture supernatant (P < 0.01). IL-22 antibody
      obviously inhibited the proliferation of RA FLS induced by NKp44+NK cells. MCP-1
      production of RA FLS was detected at 72 h after an addition of rhIL-22 (P <
      0.01). CONCLUSION: NKp44+NK cells can promote the proliferation and MCP-1
      production of RA FLS through the production of IL-22 so as to play an important
      role in the synovial proliferation and inflammation of RA.

PMID- 24731464
TI  - [Clinical significance of high sensitivity C-reactive protein for evaluating the
      efficacy of etanercept in active ankylosing spondylitis].
AB  - OBJECTIVE: To evaluate the therapeutic efficacy of etanercept for active
      ankylosing spondylitis (AS) at different levels of high sensitivity C-reactive
      protein (hs-CRP). METHODS: Patients with active AS received a subcutaneous
      injection of etanercept (50 mg, once per week) for 12 weeks. According to the
      baseline hs-CRP, they were divided into group A (hs-CRP <= 3 mg/L), group B (3 <
      hs-CRP <= 11 mg/L), group C (11< hs-CRP <= 26 mg/L) and group D (hs-CRP > 26
      mg/L). The following clinical data were recorded: VAS (visual analogue score) of
      spinal pain, time of morning stiffness, patient global assessment (PGA), BASDAI,
      BASFI, ASDAS, indices of joint tenderness on baseline and week 12. And the
      percents of ASAS20, ASAS40, ASAS partial remission, BASDAI20, BASDAI50, ASDAS
      clinically important improvement and major improvement responders were assessed
      in all groups. RESULTS: A total of 161 patients finished the study, including
      group A (n = 18), group B (n = 47), group C (n = 49) and group D (n = 47). Group
      B was similar with group A. Groups C and D were higher than group A in terms of
      ASDAS improvement score, percents of ASDAS clinically important improvement and
      major improvement responders. CONCLUSION: Patients with moderately and
      significantly elevated hs-CRP may achieve ASDAS improvement more easily than
      those with normal and mildly elevated levels.

PMID- 24731465
TI  - [Effect on the retinal fiber thickness in early diabetes].
AB  - OBJECTIVE: To observe the change of the retinal fiber layer thickness in patients
      at early stage of diabetes. METHODS: A case-control study. A total of 157
      patients with diabetes, who were divided into four groups according to the degree
      of diabetic retinopathy in fundus photos, and 40 normal patients were examined by
      optical coherence tomography (OCT). The difference among the group was assessed
      by chi(2) test, One-Way ANOVA test and LSD test. RESULTS: The superior RNFL
      around optic nerve was not statistically thinner in NDR group than normal group
      (P = 0.195) . The superior RNFL around optic nerve was statistically thinner in
      miNPDR group, moNPDR group and sNPDR group (P = 0.13,0.02,0.00) . The thickness
      of fovea in both moNPDR group and sNPDR group were thicker than normal (P =
      0.003,0.001) . In fovea, the superior RNFL was thinner in all diabetic groups (P
      < 0.01). CONCLUSION: In early stage of diabetes, the RNFL both in optic nerve and
      fovea were thinner, which would precede the microvascular changes.

PMID- 24731466
TI  - [Treatment of multiple or recurrent intracranial tumors with local chemotherapy
      by hypodermic Ommaya reservoir].
AB  - OBJECTIVE: To explore the treatment of multiple or recurrent intracranial tumors
      by hypodermic placement of Ommaya reservoir and local chemotherapy with
      methotrexate. METHODS: Retrospective analyses were performed on the clinical data
      of 45 cases with multiple or recurrent intracranial tumors at Friendship
      Affiliated Hospital, Capital Medical University from January 2010 to September
      2013. All 45 cases had a placement of Ommaya reservoir under skin. Shunt tubes
      were placed in ventricle (n = 41), cystic tumor cavity (n = 3) and tumor cavity
      (n = 1). Methotrexate was injected postoperatively into Ommaya reservoir by
      transcutaneous paracentesis. RESULTS: After local chemotherapy, head magnetic
      resonance imaging (MRI) re-examinations were performed. Tumors disappeared (n =
      32), shrunk significantly (n = 10) and had no significant improvement of symptoms
      with spinal implantation metastasis (n = 1). During chemotherapy, there were two
      mortalities due to septic shock and heart failure (n = 1 each). Follow-ups were
      conducted for 32 cases and 7 of them died. One case had operation-related
      complications. After an adjustment of shunt tube, symptoms and signs improved.
      And after local chemotherapy, tumor disappeared on MRI. CONCLUSION: The placement
      of Ommaya reservoir is mini-invasive and well-tolerated. And local chemotherapy
      with methotrexate by Ommaya reservoir is convenient and it may reduce systemic
      side effects, improve the efficacy of chemotherapy drugs, prolong survival time
      and enhance quality of life.

PMID- 24731467
TI  - [Effects on blood fat and bone density of postmenopausal women fed by soy protein
      with isoflavone].
AB  - OBJECTIVE: To explore the effects of phytoestrogen (PE) on blood lipid and bone
      density in postmenopausal women. METHODS: A total of 75 menopausal women aged 50
      70 years with estrogen reduction symptoms received an intake of soy protein
      containing 70 mg isoflavone daily in a year. Their changes of blood fat, density
      lumbar bone and sex hormone level were compared with control group without an
      intake. RESULTS: The changes of blood triglyceride (TG), total cholesterol (TC)
      and low-density lipoprotein (LDL) in two groups before and after a year showed no
      statistical significance.High-density lipoprotein (HDL) decreased in control
      group while it had no significant change in the study group. Bone densities in
      two groups showed a downward trend by an annual rate of 1%-4%, the changes in two
      groups showed no statistical significance.E2 increased slightly over basic value
      in the study group. But it had no statistical significance. The changes of
      follicle-stimulating hormone (FSH) in two groups were also similar. CONCLUSION:
      The above soy protein preparation has no effect on hypothalamic-pituitary-ovarian
      axis and no stimulation on endometrium of uterus. But it may improve the profile
      of HDL.

PMID- 24731468
TI  - [Involvement of chemokine CXCL16 in myocardial infarction and its influence on
      phagocytic activity of macrophage in vitro].
AB  - OBJECTIVE: To explore whether chemokine CXCL16 is up-regulated after myocardial
      infarction and promotes the phagocytic activity of macrophage in vitro. METHODS:
      Forty wild-type mice were randomly separated into 2 groups (n = 20 each). Group A
      had the ligation of left anterior descending coronary artery while group B
      underwent a sham operation. Electrocardiogram was used to assess whether the
      operation was successful or not. Three days after surgery, 10 animals of each
      group were sacrificed and the serum level of CXCL16 was detected by enzyme-linked
      immunosorbent assay (ELISA). Twenty-eight days after surgery, cardiac function of
      the remaining mice was measured by small animal ultrasound. Then the animals were
      sacrificed. Hematoxylin and eosin (HE) staining and immunohistochemical staining
      of cardiac paraffin section were used to observe the inflammation and detect the
      expression of CXCL16 in cardiac tissue after myocardial infarction. To explore
      the function of CXCL16 in vitro, primary murine monocytes were separated from
      bone marrow, cultured to differentiate into macrophages and transfected with
      adenovirus vectors over-expressing CXCL16 or control adenovirus vectors. After
      stimulation by debris of cardiac cells, the phagocytic uptake by macrophages was
      evaluated by flow cytometry. RESULTS: The model of myocardial infarction was
      successfully established. ELISA showed that the serum level of CXCL16 was
      elevated 3 days after myocardial infarction [(1 079 +/- 176) vs (611 +/- 37)
      pg/ml, P = 0.032]. HE and immunohistochemical staining demonstrated that the
      infiltration of macrophages increased during an early stage of myocardial
      infarction and decreased at the late stage. The CXCL16 level was up-regulated 3
      days after myocardial infarction and returned to normal level at Day 28.
      Furthermore, macrophages transfected with adenovirus over-expressing CXCL16
      showed stronger phagocytic activity compared with control (17.11% +/- 0.87% vs
      7.91% +/- 0.71%, P < 0.01). CONCLUSION: CXCL16 is up-regulated after myocardial
      infarction in mice. And an in vitro over-expression of CXCL16 promotes the
      macrophage phagocytosis of cardiac debris.

PMID- 24731469
TI  - [Changes of renal hemodynamics in dogs with endotoxemic shock].
AB  - OBJECTIVE: To explore the changes of renal hemodynamic in dogs with endotoxemic
      shock (ES) and their potential roles in acute kidney injury (AKI). METHODS:
      Canine endotoxic shock model was induced by an infusion of lipopolysaccharide of
      Escherichia coli through pulmonary artery catheter (PAC). Systemic hemodynamics
      and left renal blood flow (RBF) was monitored by PAC, pulse index continuous
      cardiac output (PiCCO) and ultrasonic blood flow meter. Blood and urine specimens
      were harvested timely for blood gas analysis, renal function tests and
      biochemical detection. RESULTS: Hemodynamics: CO and RBF fluctuated widely but
      without any significance (P > 0.05). The values of mean arterial pressure (MAP),
      systemic vascular resistance (SVR), renal vascular resistance (RVR) and 2-hour
      urine volume significantly decreased (all P < 0.05) while extravascular lung
      water (EVLW) increased markedly (P < 0.05). Renal function: There was a drop in
      CCr, urine osmotic pressure and an elevation in SCr and NAG. RBF was correlated
      positively with CO (R(2) = 0.630, P = 0.001) .However, it had no correlation with
      MAP (R(2) = 0.009, P = 0.758) . CCr was correlated positively with MAP (R(2) =
      0.415, P = 0.003) . However, it had no correlation with RBF or CO (P > 0.05 ).
      The auto-regulation curve of GFR had a shift to the right. CONCLUSION: RBF is
      positively correlated with cardiac output in endotoxin shock. Renal pressure
      perfusion may decrease obviously without any noticeable change of renal flow
      perfusion. The shift of renal auto-regulation under pressure perfusion occurs at
      the early stage of septic shock.

PMID- 24731470
TI  - [DNA hypermethylation at C/EBPalpha gene promoter relieves a PPARgamma-associated
      repression of HDAC1].
AB  - OBJECTIVE: To explore the molecular mechanisms of C/EBPalpha for regulating the
      osteogenesis of C3H10T1/2 cells. METHODS: We constructed an in vitro osteogenic
      differentiation model and investigated the mRNA and protein expression profile of
      PPARgamma2 during C3H10T1/2 osteogenesis by reverse transcription-polymerase
      chain reaction (RT-PCR) and Western blot. Next we constructed an adenovirus
      vector loading siRNA against PPARgamma2 and employed a specific antagonist of
      PPARgamma, G3335, to examine the effect of PPARgamma on activating the expression
      of C/EBPalpha. Then we performed ChIP to test PPARgamma2 binding on -1 286 bp/-1
      065 bp region of C/EBPalpha promoter and explore the role of PPARgamma in the
      dependence of histone hypoacetylation on DNA methylation in -1 286 bp/-1 065 bp
      region of C/EBPalpha promoter. RESULTS: During the osteogenic differentiation,
      PPARgamma mRNA and protein expression initially increased and then decreased in
      double-phase reactions. siRNA and G3335 induced down-regulation of PPARgamma
      activity inhibited C/EBPalpha in C3H10T1/2 cells up-regulation of osteogenic
      differentiation. ChIP results show that DNA methylation could weaken the binding
      section PPARgamma2 to -1 286 bp/-1 065 bp capabilities. CONCLUSION: This study
      provides a deeper insight into the molecular mechanisms underlying the
      osteogenesis of MSCs regulated by C/EBPalpha in synergy with PPARgamma. PPARgamma
      contributes to C/EBPalpha expression through binding on -1 286 bp/-1 065 bp
      region of its promoter during the osteogenesis of C3H10T1/2 cells. And DNA
      hypermethylation in-1 286 bp/-1 065 bp region during the terminal stage of
      osteogenesis prevents PPARgamma from binding on it so that PPARgamma-associated
      repression of HDAC1 is relieved to down-regulate the acetylation status of -1 286
      bp/-1 065 bp region. Meanwhile DNA methylation and histone acetylation are linked
      by PPARgamma for regulating the differentiation of MSCs.

PMID- 24731471
TI  - A systematic review of salvage therapy to patients with metastatic colorectal
      cancer previously treated with fluorouracil, oxaliplatin and irinotecan +/-
      targeted therapy.
AB  - Oxaliplatin, irinotecan and 5-fluorouracil in combination with or without
      targeted therapies are well-documented treatment options for first- and second
      line treatments of metastatic colorectal cancer. However, there are much less
      data on the beneficial effect on systemic therapy in the third-line setting. We
      therefore performed a systematic review of the current literature on third or
      later lines of treatment to patients with metastatic colorectal cancer after the
      use of approved drugs or combinations. METHODS: A computer-based literature
      search was carried out using Pubmed and data reported at international meetings.
      Original studies reporting >=15 patients who had previously received 5
      fluorouracil, oxaliplatin and irinotecan were included. Furthermore, patients
      with KRAS wild type tumours should had received EGFR-directed therapy. RESULTS:
      Conventional chemotherapeutic agents as capecitabine, mitomycin C, and
      gemcitabine have limited or no activity. Retreatment with oxaliplatin might be an
      option in selected patients. In addition, rechallenge with EGFR-directed therapy
      might be a valuable strategy. Data also suggest that angiogenetic drugs may
      postpone further progression and prolong survival. Lately, regorafinib has been
      approved. In conclusion, our current knowledge is based on many retrospective
      studies, some phase II studies and very few randomized clinical trials. Further
      prospective phase III trials comparing an investigational drug or combination
      with best supportive care in third- or later lines of treatment in metastatic
      colorectal cancer are highly warranted. Identification of predictive biomarkers
      and improvement of our understanding of molecular mechanisms is crucial.

PMID- 24731472
TI  - Ultrasound (US), Ultraviolet light (UV) and combination (US+UV) assisted
      semiconductor catalysed degradation of organic pollutants in water: oscillation
      in the concentration of hydrogen peroxide formed in situ.
AB  - Application of Advanced Oxidation Processes (AOP) such as sono, photo and
      sonophoto catalysis in the purification of polluted water under ambient
      conditions involve the formation and participation of Reactive Oxygen Species
      (ROS) like .OH, HO2., O2(-), H2O2 etc. Among these, H2O2 is the most stable and
      is also a precursor for the reactive free radicals. Current investigations on the
      ZnO mediated sono, photo and sonophoto catalytic degradation of phenol pollutant
      in water reveal that H2O2 formed in situ cannot be quantitatively correlated with
      the degradation of the pollutant. The concentration of H2O2 formed does not
      increase corresponding to phenol degradation and reaches a plateau or varies in a
      wave-like fashion (oscillation) with well defined crests and troughs, indicating
      concurrent formation and decomposition. The concentration at which decomposition
      overtakes formation or formation overtakes decomposition is sensitive to the
      reaction conditions. Direct photolysis of H2O2 in the absence of catalyst or the
      presence of pre-equilibrated (with the adsorption of H2O2) catalyst in the
      absence of light does not lead to the oscillation. The phenomenon is more
      pronounced in sonocatalysis, the intensity of oscillation being in the order
      sonocatalysis>photocatalysis?sonophotocatalysis while the degradation of phenol
      follows the order
      sonophotocatalysis>photocatalysis>sonocatalysis>sonolysis>photolysis. In the case
      of sonocatalysis, the oscillation continues for some more time after
      discontinuing the US irradiation indicating that the reactive free radicals as
      well as the trapped electrons and holes which interact with H2O2 have longer life
      time (memory effect).

PMID- 24731473
TI  - The implications of hyponitroxia in cancer.
AB  - Tumors are spatially heterogeneous, with regions of relative hypoxia and
      normoxia. The tumor microenvironment is an important determinant of both tumor
      growth and response to a variety of cytotoxic and targeted therapies. In the
      tumor microenvironment, reactive oxygen species and nitric oxide (NO) are
      important mediators of the level of expression of many transcription factors and
      signaling cascades that affect tumor growth and responses to therapy. The primary
      objective of this review is to explore and discuss the seemingly dichotomous
      actions of NO in cancer biology as both a tumor promoter and suppressor with an
      emphasis on understanding the role of persistently low NO concentrations or
      hyponitroxia as a key mediator in tumor progression. This review will also
      discuss the potential role of hyponitroxia as a novel therapeutic target to treat
      cancer and outline an approach that provides new opportunities for
      pharmacological intervention. 

PMID- 24731474
TI  - Reliability of pH measurement and the auscultatory method to confirm the position
      of a nasogastric tube.
AB  - BACKGROUND: Blind placement of a nasogastric feeding tube is a common nursing
      procedure. Confirmation of the correct position in the stomach is warranted to
      avoid serious complications such as misplacement in the lung. Testing pH of
      aspirate from a tube is one of the techniques to confirm the tip position. The
      purpose of this study was to evaluate the auscultatory method and pH measurement
      with a pH cut-off point of 5.5 after tube insertion and to compare this with the
      'gold standard': an abdominal X-ray. Also the feasibility of the pH method was
      evaluated. MATERIALS AND METHODS: Large prospective observational study in a
      general hospital. In adult hospitalised patients, the positioning of 331 feeding
      tubes was tested using two different methods to predict tube position in the
      stomach. RESULTS: In 98.9% (n=178) of aspirate samples with a pH <= 5.5, the tube
      was located in the stomach. If an aspirate could be obtained, the results of pH
      measurements showed a sensitivity of 78.4% and a specificity of 85.7%. Obtaining
      aspirate initially after placement was possible in approximately half of cases
      but after taking additional measures (including administration of air into the
      tube, side-positioning of the patient and re-aspiration after one hour) this
      increased to 81.6%. The sensitivity of the auscultatory method was 79% while the
      specificity was 61%. CONCLUSIONS: A pH of <= 5.5 from tube aspirate is adequate
      to check the position of the tube in the stomach. Additional measures improve the
      success to obtain an aspirate from the tube. The auscultatory method is
      unreliable.

PMID- 24731475
TI  - Strategies for implementing the WHO diagnostic criteria and classification of
      hyperglycaemia first detected in pregnancy.
AB  - The World Health Organization (WHO) has recently released updated recommendations
      on Diagnostic Criteria and Classification of Hyperglycaemia First Detected in
      Pregnancy which are likely to increase the prevalence of gestational diabetes
      mellitus (GDM). Any increase in the number of women with GDM has implications for
      health services since these women will require treatment and regular surveillance
      during the pregnancy. Some health services throughout the world may have
      difficulty meeting these demands since country resources for addressing the
      diabetes burden are finite and resource allocation must be prioritised by
      balancing the need to improve care of people with diabetes and finding those with
      undiagnosed diabetes, including GDM. Consequently each health service will need
      to assess their burden of hyperglycaemia in pregnancy and decide if and how it
      will implement programmes to test for and treat such women. This paper discusses
      some considerations and options to assist countries, health services and health
      professionals in these deliberations. 

PMID- 24731476
TI  - New IDF Guideline for managing type 2 diabetes in older people.

PMID- 24731477
TI  - Impact of postgraduate training on communication skills teaching: a controlled
      study.
AB  - BACKGROUND: Observation of performance followed by feedback is the key to good
      teaching of communication skills in clinical practice. The fact that it occurs
      rarely is probably due to clinical supervisors' perceived lack of competence to
      identify communication skills and give effective feedback. We evaluated the
      impact of a faculty development programme on communication skills teaching on
      clinical supervisors' ability to identify residents' good and poor communication
      skills and to discuss them interactively during feedback. METHODS: We conducted a
      pre-post controlled study in which clinical supervisors took part to a faculty
      development program on teaching communication skills in clinical practice.
      Outcome measures were the number and type of residents' communication skills
      identified by supervisors in three videotaped simulated resident-patient
      encounters and the number and type of communication skills discussed
      interactively with residents during three feedback sessions. RESULTS: 48 clinical
      supervisors (28 intervention group; 20 control group) participated. After the
      intervention, the number and type of communication skills identified did not
      differ between both groups. There was substantial heterogeneity in the number and
      type of communication skills identified. However, trained participants engaged in
      interactive discussions with residents on a significantly higher number of
      communication items (effect sizes 0.53 to 1.77); communication skills items
      discussed interactively included both structural and patient-centered elements
      that were considered important to be observed by expert teachers. CONCLUSIONS:
      The faculty development programme did not increase the number of communication
      skills recognised by supervisors but was effective in increasing the number of
      communication issues discussed interactively in feedback sessions. Further
      research should explore the respective impact of accurate identification of
      communication skills and effective teaching skills on achieving more effective
      communication skills teaching in clinical practice.

PMID- 24731478
TI  - Improving interprofessional coordination in Dutch midwifery and obstetrics: a
      qualitative study.
AB  - BACKGROUND: Coordination between the autonomous professional groups in midwifery
      and obstetrics is a key debate in the Netherlands. At the same time, it remains
      unclear what the current coordination challenges are. METHODS: To examine
      coordination challenges that might present a barrier to delivering optimal care,
      we conducted a qualitative field study focusing on midwifery and obstetric
      professional's perception of coordination and on their routines. We undertook 40
      interviews with 13 community midwives, 8 hospital-based midwives and 19
      obstetricians (including two resident obstetricians), and conducted non
      participatory observations at the worksite of these professional groups. RESULTS:
      We identified challenges in terms of fragmented organizational structures,
      different perspectives on antenatal health and inadequate interprofessional
      communication. These challenges limited professionals' coordinating capacity and
      thereby decreased their ability to provide optimal care. We also found that
      pregnant women needed to compensate for suboptimal coordination between community
      midwives and secondary caregivers by taking on an active role in facilitating
      communication between these professionals. CONCLUSIONS: The communicative role
      that pregnant women play within coordination processes underlines the urgency to
      improve coordination. We recommend increasing multidisciplinary meetings and
      training, revising the financial reimbursement system, implementing a shared
      maternity notes system and decreasing the expertise gap between providers and
      clients. In the literature, communication by clients in support of coordination
      has been largely ignored. We suggest that studies include client communication as
      part of the coordination process.

PMID- 24731480
TI  - The molar tooth sign is pathognomonic for Joubert syndrome!

PMID- 24731479
TI  - Meta-analysis on the association between pathologic complete response and triple
      negative breast cancer after neoadjuvant chemotherapy.
AB  - BACKGROUND: Triple-negative breast cancer (TNBC) is a special subtype of breast
      cancer that is characterized by poor prognosis, strong tumor invasion and a high
      pathologic complete response (pCR) to neoadjuvant chemotherapy (NAC). The pCR
      rate is a prognostic factor for TNBC. We aimed to evaluate the relationship
      between pCR and TNBC after NAC and originally tried to identify factors related
      to achieving pCR for TNBC using a meta-analysis. METHODS: We systematically
      searched the literature for pCR and breast cancer after NAC and carefully
      identified eligibility criteria. The association between pCR and breast cancer
      subtypes was estimated using Review Manager, while pCR rates for TNBC and non
      TNBC were determined using Meta-Analyst. RESULTS: This analysis included a total
      of 9,460 cases from 27 studies. The summary odds ratio estimating the
      relationship between pCR and breast cancer subtypes (TNBC vs non-TNBC) was 3.02
      (95% confidence interval (CI), 2.66 to 3.42). The TNBC pCR rate was 28.9% (95%
      CI, 27.0 to 30.8%) and the non-TNBC was 12.5% (95% CI, 11.7 to 13.4%). From
      subgroup analyses, we identified the factors associated with the highest pCR
      rates for TNBC. CONCLUSIONS: TNBC has a higher pCR rate than non-TNBC. In the NAC
      setting, these factors of platinum-containing, more than six cycles, four kinds
      of drugs, 16 weeks' treatment duration and sequential chemotherapy may contribute
      to increasing the pCR rate.

PMID- 24731481
TI  - Clinical syndromes or ciliopathies associated with molar tooth sign.

PMID- 24731482
TI  - Risk factors for intraventricular hemorrhage in term asphyxiated newborns treated
      with hypothermia.
AB  - BACKGROUND: Intraventricular hemorrhage is rare in term newborns. Severe asphyxia
      is recognized as one of the risk factors of intraventricular hemorrhage in these
      newborns. Therapeutic hypothermia, which is the only available treatment for the
      limitation of brain injury in term asphyxiated newborns, may cause fluctuations
      of cerebral blood flow, possibly placing the newborn more at risk for
      intraventricular hemorrhage. The literature regarding the incidence of
      intraventricular hemorrhage in the context of neonatal hypoxic-ischemic
      encephalopathy and hypothermia is sparse. METHODS: We present a clinical
      observation and review the literature regarding the risk factors for
      intraventricular hemorrhage in term asphyxiated newborns treated with
      hypothermia. RESULTS: We describe the clinical course of a term newborn with
      severe hypoxic-ischemic encephalopathy who developed significant intraventricular
      hemorrhage during the rewarming period after the 72-hour hypothermia. CONCLUSION:
      This newborn presented several risk factors for intraventricular hemorrhage,
      including severe asphyxia, hemodynamic instability, hemostasis disturbances,
      instrument delivery, venous sinus thrombosis, and hypoglycemia. Hypothermia and
      rewarming also may have contributed by causing fluctuations in cerebral blood
      flow.

PMID- 24731483
TI  - Brain abscess as a cause of macrocephaly in a newborn.

PMID- 24731484
TI  - Early hyperglycemia is associated with poor gross motor outcome in asphyxiated
      term newborns.
AB  - BACKGROUND: Hyperglycemia after ischemic stroke in adults and after near-drowning
      in children is associated with a poor neurological outcome. Anaerobic metabolism
      of glucose leads to buildup of lactic acid, free radical production,
      mitochondrial failure, and ultimately an increase in neurological injury. In
      asphyxiated infants, high lactate peaks are seen in the basal ganglia with
      magnetic resonance spectroscopy. Because motor disability in asphyxiated full
      term newborns often relates to injury in the basal ganglia, we hypothesized that
      hyperglycemia and associated buildup of lactic acid may lead to worse gross motor
      outcome. METHODS: Glucose, blood gas values, and demographic data were abstracted
      from the medical records of 41 term infants with asphyxia and without confounding
      diagnoses. Their Gross Motor Function Classification System scores were
      determined from the medical record or by structured telephone interviews.
      RESULTS: The outcomes of 14 infants were considered poor on the basis of death
      within the first 6 months or moderate-to-severe cerebral palsy (Gross Motor
      Function Classification System score 1-5). The other 27 infants had no gross
      motor disability (Gross Motor Function Classification System score 0). The
      highest recorded blood glucose correlated with poor outcome (P = 0.046 by
      logistic regression). Infants with hyperglycemia (blood glucose > 150 mg/dL) were
      more likely to have poor outcome (P = 0.017; odds ratio: 5.9; 95% confidence
      interval: 1.4-24.7). CONCLUSIONS: High blood glucose in the first 12 hours is
      associated with poor gross motor outcome in this cohort of asphyxiated term
      infants. Clinicians should avoid hyperglycemia in managing term infants with
      asphyxia.

PMID- 24731485
TI  - [The public healthy policy of the prevention and treatment of chronic kidney
      disease in China].

PMID- 24731486
TI  - [Common errors in the management of breast cancer in China].

PMID- 24731487
TI  - [Tubulointerstitial nephritis antigen expression in chronic kidney disease and
      its clinical significance].
AB  - OBJECTIVE: To explore tubulointerstitial nephritis antigen (TIN-ag) expression of
      chronic kidney disease (CKD) patients' renal tissue and the correlation to
      clinical phenotype. METHODS: Through digital drawing lots, a total of 77 CKD
      patients from October 2012 to February 2013 at our department were randomly
      selected. All of them underwent biopsy. Based upon their pathological findings,
      they were divided into 2 groups of minimal change disease (MCD) and non-minimal
      change disease (NMCD). The stains of hematoxylin and eosin and Masson were used
      to observe renal pathological changes and immunofluorescence for detecting the
      TIN-ag expression of kidney tissue. The serum levels of creatinine, blood urea
      nitrogen, estimated glomerular filtration rate (eGFR), 24-hour urine output, 24
      hour urine protein, alpha1-microglobulin, beta2-microglobulin, pathological
      casts, N-acetyl-beta-glucosaminidase (NAG), specific gravity and other clinical
      parameters were monitored to examine their relationship between renal tissue TIN
      ag expression. RESULTS: TIN-ag expression was distinct in renal tubular basement
      membrane of MCD patients while weak in primary focal segmental glomerulosclerosis
      (FSGS)(n = 16), IgA nephropathy (n = 23), MN (n = 14) and LN (n = 15) renal
      tissue. Immunofluorescence quantitative analysis showed that tubular TIN-ag
      fluorescence intensity of NMCD group was significantly lower than that of MCD
      group (4.84(3.02, 10.73) vs 20.79(8.19, 37.00), P < 0.01). In addition, TIN-ag
      expression in renal interstitial collagen area deposition of 0 grade group was
      higher than that of collagen area deposition 1-3 grades group (all P < 0.05).
      Serum alpha1-microglobulin and pathological urine cast, 24-hour urine protein of
      CKD patients were negatively correlated with kidney tubules TIN-ag expression (r
      = -0.312, -0.298, -0.214, all P < 0.05). Serum creatinine, blood urea nitrogen,
      serum beta2-microglobulin and eGFR of CKD patients had no significant
      correlations with TIN-ag expression (P > 0.05). TIN-ag expression of CKD patients
      with lower expression levels of NAG was significantly higher than that of normal
      levels of NAG expression. TIN-ag expression of low urine specific gravity group
      was lower than that of normal urine specific gravity group (P < 0.05).
      CONCLUSIONS: TIN-ag expression of renal tissue tubule basement membrane in NMCD
      group is significantly lower than that in MCD group. TIN-ag expression is
      negatively correlated with renal tissue fibrosis. Expression of serum alpha1
      microglobulin and concentrations of urinary pathology tube, 24-hour urine
      protein, NAG expression and urine specific gravity are negatively correlated with
      renal tissue TIN-ag expression in CKD patients.

PMID- 24731488
TI  - [Effects of core-binding factor alpha1 gene silenced by siRNA on calcification of
      vascular smooth muscle cells induced by high phosphate].
AB  - OBJECTIVE: To explore the effects of core-binding factor alpha1 (Cbfalpha-1) gene
      silenced by siRNA on osteogenic differentiation and calcification of vascular
      smooth muscle cells (VSMC) induced by high phosphate in vitro. METHODS: VSMC were
      cultured in vitro and passaged 3 to 8 times. Four pairs of Cbfalpha-1 siRNA were
      designed and synthesized. Transfection was performed with cationic lipid vectors
      (Lipofectamine 2000). Transfection conditions were optimized by the FAM
      fluorescent labeling-siRNA to screen effective siRNA sequences by reverse
      transcription-polymerase chain reaction (RT-PCR). After transfection with
      effective siRNA sequences, VSMCs were divided into 4 groups: (1) normal phosphate
      (Pi 1.3 mmol/L); (2) high phosphate (Pi 2.6 mmol/L); (3) siRNA transfection: high
      phosphate+Cbfalpha-1-siRNA; (4) negative transfection control: high
      phosphate+negative control siRNA. Cbfalpha-1 and osteopontin (OPN) mRNA and
      protein expression were detected by RT-PCR and Western blotting. Calcium
      deposition was visualized by Alizarin stain method. RESULTS: The transfection
      efficiency was around 55% with a concentration of Cbfalpha-1 siRNA 100 nmol/L and
      Lipo 8 ul/ well. Cbfalpha-1 siRNA 1952 was chosen as the effective sequence with
      a suppression ratio up to 81.8%. At 24 and 48 h post-transfection, the expression
      of Cbfalpha-1 mRNA was significantly lower in siRNA transfection group than that
      in high phosphate group (0.335 +/- 0.059 vs 0.714 +/- 0.106, 0.574 +/- 0.036 vs
      0.726 +/- 0.086, all P < 0.01) . At 48 and 72 h post-transfection, the expression
      of Cbfalpha-1 protein in siRNA transfection group was significantly lower than
      that in high phosphate group (both P < 0.01) . While Cbfalpha-1 gene was silenced
      by siRNA in siRNA transfection group, the mRNA and protein expression of OPN
      significantly declined (all P < 0.05) and calcium deposition in cell layers
      decreased. CONCLUSIONS: Cbfalpha-1 siRNA can effectively inhibit the expression
      of Cbfalpha-1 mRNA and protein in VSMC and thus suppress the transformation of
      VSMC into osteoblast-like cells and calcification induced by high phosphate.
      Cbfalpha-1 may become a potential therapeutic target in vascular calcification of
      chronic kidney disease.

PMID- 24731489
TI  - [Retrospective analysis of influence of differential protein intake on renal
      prognosis for progressive chronic kidney disease].
AB  - OBJECTIVE: To explore retrospectively the influence of differential protein
      intake on renal prognosis for progressive chronic kidney disease (CKD). METHODS:
      A total of 159 chronic kidney disease patients at stages 2, 3 and 4 were enrolled
      and a questionnaire survey was conducted from January 2009 to July 2012. They
      were followed monthly and their clinical data collected, including primary
      disease, blood pressure, body mass index and adverse events. Laboratory tests
      were performed every 3 months, including biochemical parameters, protein-energy
      malnutrition (PEM), diet reviews and daily protein intake (DPI). A simplified
      MDRD formula was employed to evaluate the level of estimated glomerular
      filtration rate (eGFR). According to the level of DPI, they were divided into 3
      groups of very low protein diet (VLPD): DPI <= 0.6 g . kg(-1) . d(-1), low
      protein diet (LPD): DPI >0.6-<0.8 g . kg(-1) . d(-1) and normal-protein diet
      (NPD): DPI >= 0.8 . g . kg(-1) . d(-1). RESULTS: Among them, 4 cases (2.50%)
      progressed to uremia stage and received renal replacement therapy, 2(1.25%)
      experienced rapid decline in renal function, 9(5.66%) were hospitalized from
      cardio-cerebral diseases and the 2-year kidney survival rate was 97.5%. At the
      end of study, among 9 patients of PEM, 2 subjects had a serum level of albumin
      under 32 g/L and another 7 with a BMI<20 kg/m(2). No significant difference
      existed in PEM among different stages of CKD. There was no significant
      correlation between DPI and Delta GFR (all P > 0.05). CONCLUSION: Within a
      certain range, differential protein intake may not significantly affect the
      prognosis of kidney for progressive CKD patients.

PMID- 24731490
TI  - [Patterns of liver metastasis and treatment outcomes of Chinese patients with
      hormonal receptor positive breast cancer].
AB  - OBJECTIVE: To explore the clinical characteristics and prognosis of estrogen
      receptor/progesterone receptor (ER/PR) positive breast cancer (luminal subtype)
      patients with liver metastases. METHODS: A total of 182 patients with liver
      metastasis from luminal subtype breast cancer between January 2000 and December
      2011 were retrospectively reviewed. Their clinical characteristics, treatments
      and prognosis were collected and analyzed. RESULTS: Their median age was 47 years
      and 118 patients were younger than 50 years old. The median disease-free survival
      (DFS) after primary operation of breast cancer was 19.5 months. All patients
      received first-line chemotherapy for liver metastases. Overall response (CR+PR)
      rate was 60.4% (110/182) . Progression-free survival (PFS) and overall survival
      (OS) were 8 and 23 months respectively. The median OS was extended by 7 months in
      younger patients ( <= 50) than in older ones (>50) (P < 0.05). In addition, PFS
      and OS were also extended by 3 and 7 months in patients with complete and partial
      responses than those who had stable and progressive diseases (P < 0.05). No
      difference existed in PFS and OS with or without capecitabine-based regimens(both
      P > 0.05). CONCLUSION: Age and response to treatment are independent prognostic
      factors for ER and/or PR positive breast cancer patients with liver metastasis.

PMID- 24731491
TI  - [Prediction value for dynamic changes of circulating tumor cell in therapeutic
      response and prognosis of Chinese metastatic breast cancer patients].
AB  - OBJECTIVE: To explore the prediction value for dynamic changes of circulating
      tumor cell (CTC) in therapeutic response and prognosis of Chinese metastatic
      breast cancer patients. METHODS: A total of 300 metastatic breast cancer patients
      from six breast cancer centers in China were included from March 2010 to January
      2011. The CTC levels of metastatic breast cancer patients were detected with a
      CellSearch system before starting a new systemic therapy (baseline) and after 3
      4, 6-8 weeks. The progression-free survival (PFS) of different groups according
      to dynamic changes of CTC was estimated by the Kaplan-Meier method and compared
      with Log-Rank test. RESULTS: The median follow-up time was 36.86 weeks. The
      median PFS of patients with >= 5 CTCs/7.5 ml at baseline but with < 5 CTCs/7.5 ml
      after treatment of 3-4 weeks was significantly prolonged than that those with
      persistent >= 5 CTCs/7.5 ml at the same timepoint (30.4 vs 14.1 weeks, P =
      0.010). Furthermore, the median PFS of former had no significant statistic
      difference with those with < 5 CTCs/7.5 ml at baseline (30.4 vs 42.0 weeks, P =
      0.780). The analysis result of PFS for three groups according to CTC of 6-8 weeks
      treatment was consistent with that according to CTC of 3-4 weeks. The median PFS
      of patients with >= 5 CTCs/7.5 ml at baseline but with < 5 CTCs/7.5 ml after
      treatment of 6-8 weeks was significantly prolonged than that those with
      persistent >= 5 CTCs/7.5 ml at the same time point (33.4 vs 8.9 weeks, P =
      0.000). The median PFS of former had no significant statistic difference with
      those with < 5 CTCs/7.5 ml at baseline(33.4 vs 42.0 weeks, P = 0.950).
      CONCLUSION: The dynamic changes of CTC levels during therapy may predict an
      improvement of progression disease risk and has significance in therapeutic
      efficacy monitoring.

PMID- 24731492
TI  - [Clinical observations of ductal carcinoma in situ and early stage breast cancer
      with invasive depth less than 1 cm].
AB  - OBJECTIVE: To explore the clinical characteristics and prognosis of ductal
      carcinoma in situ (DCIS) and early stage ductal breast cancer with invasive depth
      <= 1 cm. METHODS: Follow-up analyses were performed for the clinical data of 57
      patients with DCIS, 46 with pT(1mic) and 74 with pT(1a-b) breast cancer treated
      or consulted at our hospital. Single factor analysis was used to examine their
      prognostic factors. RESULTS: Among them, estrogen receptor (ER), progesterone
      receptor (PR), human epidermal growth factor receptor 2(HER-2) positive rate and
      visual tumor size (2.0(0.1-7.0) vs 2.0(0.5-10.0) vs 2.0(0.3-10.0) cm)had no
      statistical differences between 3 groups (all P > 0.05). After median follow-up
      periods of 63, 38, 59 months, 12 patients suffered recurrence and metastasis and
      the rate of each group had no statistical differences. For pT(1a-b) patients with
      positive hormone receptor, endocrine therapy markedly reduced the risk of
      recurrence and metastasis (P = 0.024) . pT(1mic), pT(1a-b) patients on
      chemotherapy had higher or comparable recurrence rate versus those without. And
      DCIS patients on chemotherapy had a much higher recurrence rate (P = 0.016) . In
      pT(1a-b) group, HER-2 positive patients had higher recurrence and metastasis
      rates. Yet there was a decreasing tendency after Herceptin treatment.
      CONCLUSIONS: Chemotherapy without proper indications may not improve the
      prognosis of DCIS, pT(1mic) and pT(1a-b) patients. Endocrine therapy is the
      crucial prognostic factor of patients with positive hormone receptor. Use of
      Herceptin for HER-2-positive patients is probably significant.

PMID- 24731493
TI  - [Biological and clinical implications of aromatase inhibitors in early male
      breast cancer patients].
AB  - OBJECTIVE: To evaluate the efficacy, biological behaviors and safety of aromatase
      inhibitors in early male breast cancer. METHODS: A total of 12 male breast cancer
      patients of stages I and II took aromatase inhibitors. Their levels of estradiol
      were measured before and after medication. Another 12 patients received tamoxifen
      as controls. The recurrence, mortality and side effects were monitored and
      analyzed. RESULTS: Their 5-year disease-free survival rates were 69.4%, 77.0% and
      5-year overall survival rates 75.0%, 83.4% respectively. No drug withdrawal
      occurred because of side effects. No inter-group statistical significance existed
      in estrogen receptor (9 vs 10 cases), progesterone receptor (10 vs 9 cases ),
      human epidermal growth factor receptor 2 (2 vs 3 cases ), stage T, N, M and
      disease-free survival rate, disease related 5-year overall survival rate (both P
      > 0.05) . There was statistical difference in the level of estradiol before and
      after medication. The level of estradiol was initially <5 ng/L in one patient,
      but rose during disease progression. CONCLUSIONS: The efficacy of aromatase
      inhibitors and tamoxifen in early male breast cancer patients is comparable. And
      the activity of aromatase inhibitors is correlated with a significantly reduced
      level of E(2) level. Some patients may develop secondary resistance.

PMID- 24731494
TI  - [Analysis of clinical characteristics for large granular lymphocytic leukemia].
AB  - OBJECTIVE: To explore the clinical and laboratory characteristics for large
      granular lymphocytic leukemia (LGL). METHODS: A total of 35 LGL patients were
      retrospectively analyzed from March 2004 to May 2013 at our department. RESULTS:
      Their median age of diagnosis was 51 years. The anemia-related symptoms included
      splenomegaly (n = 11, 31.4%). And one patient (2.8%) with a history of rheumatoid
      arthritis. Anemia was the most frequent hematological abnormality (n = 27,
      77.1%). The range of LGL count in peripheral blood was (0.82-23.7) *10(9)/L.
      Among them, 19 patients (54.2%) showed the CD3(+)CD57(+) CD56(-)indolent LGL
      phenotype. Two patients showed complex karyotype. T cell receptor beta chain
      variable region (TCRVbeta) analysis was positive in 8 patients. The median
      overall survival of aggressive LGL patients was significant shorter than that of
      indolent patient(16 months vs not reached, P = 0.000). Univariate analysis showed
      the median overall survival of patients with B symptom was significant shorter
      than that without B symptom (19 vs 45 months, P = 0.039); the median overall
      survival of patients with thrombocytopenia was significant shorter than that with
      platelet normal (16 vs 42 months, P = 0.000). Multivariate analysis showed B
      symptom (P = 0.736) and thrombocytopenia (P = 0.977) at diagnosis were not
      prognostic factors. CONCLUSIONS: Chinese LGL patient with rheumatoid arthritis is
      infrequent compared with foreign reports. TCRVbeta analysis is important for its
      diagnosis. The overall survival of aggressive LGL patients is significantly
      inferior to indolent patients, and need earlier intensive therapy in order to
      achieve longer survival.

PMID- 24731495
TI  - [Influencing factors of anxiety and depression in asthmatics].
AB  - OBJECTIVE: To explore the major influencing factors for asthmatics with anxiety
      and depression. METHODS: A total of 176 physician-diagnosed asthmatics were
      confirmed from March 2011 to March 2012 at First Affiliated Hospital of Zhengzhou
      University. And 144 were finally screened to examine their demographic
      characteristics and clinical features. Their status of anxiety and depression and
      the levels of control were evaluated with the scores of self-rating anxiety scale
      (SAS), self-rating depressive scale (SDS) and asthma control test (ACT). Firstly,
      asthma with anxiety and asthma with depression as a dependent variable, general
      demographics and clinical characteristics as independent variables, single-factor
      analysis revealed the relevant factors of asthma with anxiety and depression;
      secondly, multi-variable Logistic regression analysis was performed to examine
      the major influencing factors of anxiety and depression in asthmatics based on
      the relevant factors as independent variables. RESULTS: Multiple variables
      Logistic regression showed that residing place (rural vs city/town, OR = 0.28);
      control levels (partly controlled vs uncontrolled, OR = 0.22; control vs non
      control, OR = 0.10); severity (secondary vs first level, OR = 1.42; third vs
      first level, OR = 2.32; forth vs first level, OR = 3.12) were the major
      influencing factors of anxiety (all P < 0.05). Meanwhile, age (31-45 vs <= 30
      years, OR = 11.35; >45 vs <= 30 years, OR = 18.73); level of education (junior
      high vs primary school and below, OR = 3.30; high/secondary vs primary school and
      below, OR = 3.52; college and above vs primary school and below, OR = 3.60),
      medical history (1-3 years vs <1 year, OR = 2.68; >3 years vs <1 year, OR =
      3.01); control levels (partial control vs uncontrolled, OR = 0.25; controlled vs
      uncontrol, OR = 0.18) were the major influencing factors of depression (all P <
      0.05). CONCLUSIONS: Rural dwelling, poorly controlled and severe asthmatics are
      more likely to associate with anxiety. And depression moods are more common in
      those with an elder age, a long course of disease, higher education and poor
      control.

PMID- 24731496
TI  - [The risks of long-term proton pump inhibitors use].
AB  - OBJECTIVE: To explore the risks of long-term proton pump inhibitors (PPI) use.
      METHODS: A total of 79 study subjects were selected from patients seeking health
      care at outpatient gastroenterology clinic at Peking University People's Hospital
      during January 2011 to June 2013. Long-term PPI use was defined as taking PPI for
      at least one year. They were divided into study (n = 79) and control (n = 47)
      groups after matching for age and gender. The study group had 43 females and 36
      males with an average age of (63 +/- 10) years. And the control group had 28
      females and 19 males with an average age of (63 +/- 9) years. Data collected were
      demographic characteristics, clinical diagnosis, detailed dosing information of
      PPI. serum hemochrome, serum gastrin, vitamin B(12), serum iron, magnesium,
      calcium, copper, zinc, bone density of hip joint and lumbar vertebra L(1-4).
      Statistic analysis was performed with SPSS software (t and chi(2) test). RESULTS:
      The medium duration of PPI use was 3.07(1-15) years. Daily usage was a full or
      half amount of pharmaceutical directed dosage. Questionnaires regarding appetite,
      defecation, infection, otalgia change in long-term PPI use indicated:among them,
      77(97.5%) cases had no appetite change and 2 (2.5%) improved. And 73 cases
      (92.4%) had no change or 2 cases improved (2.5%) in bowel movements habits while
      another 4 cases (5.1%) changed into loose stools. Lung or intestinal infection
      was not found. No case had an onset of otalgia related with PPI intake. Among PPI
      users, 14 cases (17.7%) appeared to have gastric polyps. T value of total bone
      density of hip and inter-hip was -0.93 +/- 1.04 and -0.61 +/- 0.91 respectively
      in the study group. And both were lower than those in the control group (-0.44 +/
      1.12, -0.19 +/- 0.94; t = -2.49, -2.35; P = 0.014, 0.021). No statistical
      differences existed in T value of neck of hip, as well as total T value and T
      value of each L(1-4) between study and control groups (all P > 0.05). Higher
      serum Mg compared to control group ((1.03 +/- 0.08) vs (0.97 +/- 0.07) mmol/L, t
      = 4.13, P = 0.000). No difference of serum calcium, copper, iron, zinc, vitamin
      B(12), folic acid and Hb,MCV,MCH between study and control groups (all P > 0.05).
      Higher serum gastrin versus normal range and controls were found in the study
      group ((108 +/- 28) vs 100 vs (79 +/- 26) ng/L, t = 2.56, 5.78; both P < 0.05).
      Taking manual routine dosage have higher hip and lumbar osteoporosis than half
      dosage, and bone density decreased and normal bone density ratios are lower(all P
      < 0.05). CONCLUSIONS: Long-term use of PPI with small or average dosage may
      slightly decrease hip density and increase serum gastrin. However, there is
      little effect on vitamin B(12) and minerals.

PMID- 24731497
TI  - [Surgical treatment of bone metastases from renal cell carcinoma].
AB  - OBJECTIVE: To retrospectively analyze the survival of renal cell carcinoma
      patients with bone metastases, evaluate the effect of treatment and identify the
      prognostic factors in these patients. METHODS: A total of 66 renal cell carcinoma
      patients with bone metastases treated at our hospital between October 1990 and
      October 2010 were divided into 3 groups: solitary bone metastasis referred for
      radical surgery (n = 19); palliative surgery for solitary/multiple bone
      metastasis (n = 31); extraosseous metastasis without orthopedic surgery (n = 16).
      The effects of different variables on survival were determined according to the
      Kaplan-Meier method and Log-Rank test. And Cox proportional hazard regression
      model was used to estimate the prognostic factors. RESULTS: Their mean follow-up
      period was 25 (6-68) months. The survival significantly improved if bone
      metastases were solitary (45 vs 29 and 13 months, both P < 0.01), there was no
      vertebral bone involvement (31 vs 10 months, P < 0.01) and radical surgery was
      performed (50 vs 28 and 13 months, both P < 0.01). Age, gender, tumor size,
      alkaline phosphatase and lactate dehydrogenase had no effect on survival (all P >
      0.05). Based on Cox regression analysis, survival was influenced by the number of
      metastasis foci (RR = 0.259, 95%CI:0.075-0.897) , type of procedure (RR = 17.845,
      95%CI:4.246-74.992) and vertebral bone involvement (RR = 4.526, 95%CI:1.896
      10.803) (all P < 0.05). CONCLUSIONS: Surgery is a better option for achieving
      local tumor control, providing good function and increasing the survival of
      patients with bone metastases. And radical resection is indicated for the
      patients with a solitary metastasis.

PMID- 24731498
TI  - [Clinical research of no use of antibiotics in patients undergoing tension-free
      repair with incarcerated inguinal hernia].
AB  - OBJECTIVE: To explore the safety in inguinal incarcerated hernia repair without
      use of antibiotics. METHODS: Retrospective statistical analysis was performed for
      a total 326 patients with inguinal incarcerated hernia repair at our hospital
      from January 2011 to July 2013. They were divided into 2 groups of non-using (n =
      192) and using (n = 134) antibiotics. Statistical analysis of early postoperative
      infection was performed for two groups. RESULTS: The total incision infection had
      no statistical difference between two groups (7.29% (14/192) vs 3.73% (5/134),
      0.52% (1/192) vs 1.49% (2/134), both P > 0.05). Further comparison of leukocyte
      count and neutrophil count at Day 3 showed no inter-group statistical difference
      ((7.9 +/- 0.6) *10(9) vs (7.8 +/- 0.7) *10(9)/L, (4.9 +/- 0.5)*10(9) vs (5.0 +/-
      0.5) *10(9)/L; U = 1.344, 1.777; P = 0.180, 0.077). CONCLUSION: It is unnecessary
      to use preventive antibiotics in patients undergoing tension-free repair with
      incarcerated inguinal hernia without high-risk infection or bowel necrosis.

PMID- 24731499
TI  - [Effects of interleukin-6 in epithelial-mesenchymal transition of Barrett's
      esophagus cells].
AB  - OBJECTIVE: To explore whether the stimulation of interleukin-6 (IL-6) could
      induce Barrett's esophagus cells (CP-D) to undergo epithelial-mesenchymal
      transition (EMT). METHODS: IL-6 was used to treat CP-D cell line at the
      concentrations of 0, 10, 20, 50 and 100 ug/L. The cell morphological changes were
      observed after 24 hour. Reverse transcription (RT)-PCR, wound healing assay and
      transwell assay was used to test the migratory potentials of CP-D cell. Western
      blot and immunofluorescence methods were performed to detect the expression of E
      cadherin and vimentin. RESULTS: After 24-hour exposure of IL-6, CP-D cell lost
      its polarity and had reduced cell-to-cell adhesion connection. Wound healing
      assay showed the number of migrating cells was 131 +/- 22 in 0 ug/L group, lesser
      than 10, 20, 50 and 100 ug/L group (328 +/- 47, 347 +/- 59, 483 +/- 62, 492 +/-
      55, all P < 0.05). Transwell experiments indicated that IL-6 could enhance the
      invasiveness of CP-D (62 +/- 11, 67 +/- 15, 97 +/- 12, 99 +/- 13 vs 13 +/- 5, all
      P < 0.05) . Real-time RT-PCR revealed that increasing concentrations of IL-6 led
      to a reduction of E-cadherin mRNA expression and an enhancement of vimentin mRNA
      expression. And significant differences were detected between 20 and 50 ug/L
      (0.79 +/- 0.07 vs 0.47 +/- 0.16, P = 0.012; 1.43 +/- 0.15 vs 1.78 +/- 0.37, P =
      0.026). The results of Western blotting were consistent with those of real-time
      RT-PCR. It indicated that 50 ug/L was the most optimal concentration of IL-6 for
      inducing EMT in CP-D. CONCLUSIONS: IL-6 stimulation may induce CP-D to undergo
      EMT. As a result, its invasiveness and migration capacity becomes enhanced so as
      to lead to malignant transformation.

PMID- 24731500
TI  - [Effects of methylprednisolone plus Xuebijing on bleomycin-induced acute
      exacerbation of pulmonary fibrosis in rats].
AB  - OBJECTIVE: To explore the effect of Xuebijing plus methylprednisolone in a rat
      model of pulmonary fibrosis induced by bleomycin. METHODS: Eighty Wistar rats
      were randomly divided into 5 groups of control, model control, Xuebijing,
      methylprednisolone and combined treatment (Xuebijing plus methylprednisolone).
      Pulmonary fibrosis model was induced by an intra-tracheal injection of bleomycin.
      The treatment groups were administrated with 4.5 ml . kg(-1) . d(-1) Xuebijing
      and 4.5 ml . kg(-1) . d(-1) physiologic saline, 4.5 ml . kg(-1) . d(-1)
      methylprednisolone and 4.5 ml . kg(-1) . d(-1) physiologic saline, or 4.5 ml .
      kg(-1) . d(-1) methylprednisolone and 4.5 ml . kg(-1) . d(-1) Xuebijing
      respectively by intraperitoneal injection. And the control and model control
      groups received 9 ml . kg(-1) . d(-1) physiological saline. The animals were
      sacrificed at Days 14 and 28 respectively. The degrees of lung inflammation and
      pulmonary fibrosis were detected by hematoxylin & eosin and Masson staining. The
      serum levels of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha)
      were assessed by enzyme-linked immunosorbent assay (ELISA). The expression of
      transforming growth factor-beta1 (TGF-beta1) in lung tissue was evaluated by
      immunohistochemical staining. RESULTS: Compared between the combined treatment
      and model control groups, at Days 14 and 28, the degree of alveolitis ((1.09 +/-
      0.30) vs (2.03 +/- 0.25) and (0.75 +/- 0.27) vs (1.78 +/- 0.36) ng/L) , the
      degree of pulmonary fibrosis ((0.91 +/- 0.19 )vs (1.34 +/- 0.23) and (0.75 +/-
      0.27) vs (1.78 +/- 0.36)) . The expression of TGF-beta1 in lung tissue ((12.11 +/
      3.06)% vs (17.70 +/- 2.70)% & (10.96 +/- 2.53)% vs (16.72 +/- 2.20)%). And the
      serum level of TNF-alpha ((68.39 +/- 9.28) vs (90.94 +/- 11.16) ng/L & (67.14 +/-
      10.88) vs (81.73 +/- 7.23) ng/L) all significantly decreased (all P < 0.05). At
      Day 14, the serum level of IL-6 in the combined treatment group significantly
      decreased as compared with the model control group ((199 +/- 31) vs (250 +/-
      43)ng/L, P = 0.036). At Day 28, no statistic difference was found ( (192 +/- 25)
      vs (227 +/- 24)ng/L, P = 0.058). CONCLUSIONS: The combined treatment of
      methylprednisolone and Xuebijing is more effective in a rat model of pulmonary
      fibrosis. And its mechanism is associated with the reduced levels of IL-6 and TNF
      alpha and TGF-beta1 expression in lung tissue.

PMID- 24731501
TI  - [Protective effect and mechanisms of pituitrin on acute paraquat-induced lung
      injury in rats].
AB  - OBJECTIVE: To explore the protective effect of pituitrin on the development of
      paraquat-induced lung injury in rats. METHODS: Sixty healthy Sprague Dawley
      female rats were randomized into 3 groups of control, paraquat and treatment (80
      mg/kg, intragastric) groups (n = 20 each) Each group was divided into 4, 6, 12
      and 24 h subgroups (n = 5 each). The treatment group received pituitrin,
      injection via internal jugular vein 30 minutes after paraquat dosing. As
      controls, control and paraquat groups were injected with an equal volume of
      saline. The paraquat content in serum and lung tissue was measured by high
      performance liquid chromatography-mass spectrometry (HPLC-MS). And the levels of
      tumor necrosis factor-alpha (TNF-alpha) in sera and nuclear factor-kappa B (NF
      kappaB) in lung tissue and the content of protein in bronchoalveolar lavage (BAL)
      fluid were detected at various timepoints. Lung wet-to-dry weight ratio (W/D) was
      recorded after pituitrin dosing. In addition, pathological changes were also
      observed. RESULTS: The highest drug concentration of paraquat in lung tissue was
      far lower in the treatment group than that in the paraquat group ((7.67 +/- 0.91)
      vs (13.27 +/- 0.95) ug/g, P = 0.002). There were the same result in sera ((1 695
      +/- 274) vs (5 377 +/- 576) ng/ml, P = 0.003). The area under the concentration
      time curve in the treatment group was significantly lower than that in the
      paraquat group (10 482 vs 43 441, P = 0.000). The levels of NF-kappaB in lung
      tissue and TNF-alpha in sera in the treatment group were lower than those in the
      paraquat group (TNF-alpha: 24 h: (1.85 +/- 0.22) vs (2.59 +/- 0.13) ng/ml, P =
      0.020; NF-kappaB: 24 h: (88.0 +/- 2.7) vs (101.8 +/- 2.8) ng/g, P = 0.003). And
      there was a decrease in the content of protein in BAL fluid in the treatment
      group versus the paraquat group (BALF protein: 24 h: (125.9 +/- 4.2) vs (192.7 +/
      6.5)ug/ml, P = 0.003), lung W/D significantly decreased in the treatment group
      versus the paraquat group (12 h: 3.50 +/- 0.14 vs 3.73 +/- 0.15, P = 0.043; 24 h:
      3.41 +/- 0.06 vs 3.61 +/- 0.09, P = 0.047). In addition, when compared with the
      paraquat group, the pituitrin-treated rats showed a mitigation of inflammatory
      response in lungs and reduced pulmonary edema. CONCLUSION: Pituitrin treatment
      decreases the content of paraquat in sera and lung homogenate in intoxicated rats
      and alleviates lung injury so that it may become a useful adjuvant in the
      treatment of acute lung injury.

PMID- 24731502
TI  - Association of lipocalin-type prostaglandin D synthase with disproportionately
      enlarged subarachnoid-space in idiopathic normal pressure hydrocephalus.
AB  - BACKGROUND: Idiopathic normal pressure hydrocephalus (iNPH) is a treatable cause
      of dementia, gait disturbance, and urinary incontinence in elderly patients with
      ventriculomegaly. Its unique morphological feature, called disproportionately
      enlarged subarachnoid-space hydrocephalus (DESH), may also be a diagnostic
      feature. Lipocalin-type prostaglandin D synthase (L-PGDS) is a major
      cerebrospinal fluid (CSF) protein produced by arachnoid cells, and its
      concentration in the CSF is reportedly decreased in iNPH. L-PGDS acts as a
      prostaglandin D2-producing enzyme and behaves as a chaperone to prevent the
      neurotoxic aggregation of amyloid beta (Abeta) implicated in Alzheimer's disease,
      a major comorbidity of iNPH. The aim of this study was to confirm the L-PGDS
      decrease in DESH-type iNPH and to clarify its relationship with clinico
      radiological features or other CSF biomarkers. METHODS: We evaluated 22 patients
      (age: 76.4 +/- 4.4 y; males: 10, females: 12) referred for ventriculomegaly
      without CSF pathway obstruction, and conducted a CSF tap test to determine the
      surgical indication. CSF concentrations of L-PGDS, Abeta42, Abeta40, and total
      tau (t-tau) protein were determined using enzyme-linked immunosorbent assays.
      Clinical symptoms were evaluated by the iNPH grading scale, mini-mental state
      examination, frontal assessment battery (FAB), and timed up and go test. The
      extent of DESH was approximated by the callosal angle, and the severity of
      parenchymal damage was evaluated by the age-related white matter change (ARWMC)
      score. RESULTS: L-PGDS and t-tau levels in CSF were significantly decreased in
      DESH patients compared to non-DESH patients (p = 0.013 and p = 0.003,
      respectively). L-PGDS and t-tau showed a significant positive correlation
      (Spearman r = 0.753, p < 0.001). Among the clinico-radiological profiles, L-PGDS
      levels correlated positively with age (Spearman r = 0.602, p = 0.004), callosal
      angle (Spearman r = 0.592, p = 0.004), and ARWMC scores (Spearman r = 0.652, p =
      0.001), but were negatively correlated with FAB scores (Spearman r = 0.641, p =
      0.004). CONCLUSIONS: Our data support the diagnostic value of L-PGDS as a CSF
      biomarker for iNPH and suggest a possible interaction between L-PGDS and tau
      protein. In addition, L-PGDS might work as a surrogate marker for DESH features,
      white matter damage, and frontal lobe dysfunction.

PMID- 24731503
TI  - "Just culture": is radiology ready?

PMID- 24731504
TI  - Encouraging women into the new diagnostic radiology/interventional radiology
      pathway.

PMID- 24731505
TI  - Marine metaproteomics: deciphering the microbial metabolic food web.
AB  - Metaproteomics can be applied to marine systems to discover metabolic processes
      in the ocean. This review describes current breakthroughs regarding marine
      microbes in the areas of microbial procurement of nutrients, important and
      previously unrecognized metabolic processes, functional roles for proteins with
      previously unknown functions, and intricate networks of metabolic interactions
      between symbiotic microbes and their hosts. By recognizing that metaproteomics
      empowers our understanding of the roles that marine microbes play in global
      biogeochemical cycles, the achievements to date from this advancing field
      highlight the enormous potential that the future holds. 

PMID- 24731506
TI  - Cost-effectiveness of enzyme replacement therapy for type 1 Gaucher disease.
AB  - OBJECTIVE: To evaluate the cost-effectiveness of enzyme replacement therapy (ERT)
      compared to standard medical care without ERT in the Dutch cohort of patients
      with type 1 Gaucher disease (GD I). DESIGN: Cost-effectiveness analysis was
      performed using a life-time state-transition model of the disease's natural
      course. Transition probabilities, effectiveness data and costs were derived from
      retrospective data and prospective follow-up of the Dutch study cohort. SETTING:
      The tertiary referral center for Gaucher disease in the Netherlands.
      PARTICIPANTS: The Dutch cohort of patients with GD I. INTERVENTION: ERT versus
      standard medical care without ERT in symptomatic patients. MAIN OUTCOME MEASURES:
      Years free of end organ damage (YFEOD) (splenectomy, bone complication,
      malignancy, multiple complications), quality adjusted life years (QALY), and
      costs. RESULTS: Over an 85 year lifetime, an untreated GD I patient will generate
      48.9 YFEOD and 55.86 QALYs. Starting ERT in a symptomatic patient increases the
      YFEOD by 12.8 years, while the number of QALYs gained increases by 6.27. The
      average yearly ERT medication costs range between ? 124,000 and ? 258,000 per
      patient. The lifetime costs of ERT starting in the symptomatic stage are ?
      5,716,473 against ? 171,780 without ERT, a difference of ? 5,544,693.
      Consequently, the extra costs per additional YFEOD or per additional QALY are ?
      434,416 and ? 884,994 respectively. After discounting effects by 1.5% and costs
      by 4% and under a reasonable scenario of ERT unit cost reduction by 25%, these
      incremental cost-effectiveness ratios could decrease to ? 149,857 and ? 324,812
      respectively. DISCUSSION: ERT is a highly potential drug for GD I with
      substantial health gains. The conservatively estimated incremental cost
      effectiveness ratios are substantially lower than for Pompe and Fabry disease. We
      suggest that the high effectiveness has contributed importantly to acceptance of
      reimbursement of ERT for GD I. The present study may further support discussions
      on acceptable price limits for ultra-orphan products.

PMID- 24731507
TI  - Determination of body segment masses and centers of mass using a force plate
      method.

PMID- 24731508
TI  - Severely restricted diets in the absence of medical necessity: the unintended
      consequences.

PMID- 24731509
TI  - Perspectives of cultural competency from an international service learning
      project.

PMID- 24731510
TI  - The progression of the tubulointerstitial fibrosis driven by stress-induced
      "proliferation-death" vicious circle.
AB  - Several hypotheses have been developed to interpret the progression of
      tubulointerstitial fibrosis (TF), including senescence, epithelial-mesenchymal
      transition, inflammation, chronic hypoxia, and reactive oxygen species. All of
      these hypotheses are based on persistent cell injury and localized cell death.
      Proliferation of neighboring renal tubular epithelial cells (RTECs) is beneficial
      for organ function recovery from acute injury. However, compensatory
      proliferation is not always advantageous, as the proliferating cells are
      vulnerable to ongoing detrimental stimuli, such as inflammation, endocrine
      stress, high blood pressure, hypoxia/ischemia, and the like. Cell injury and
      death promotes secretion of growth factors, which evokes proliferation of RTECs;
      entering the cell cycle makes the RTECs more vulnerable to injury and death.
      Under persistent stress, death and proliferation are mutually promoted and form
      the vicious circle that triggers, maintains, and augments the inflammation and
      progression of TF. We hypothesize that the "proliferation-death" circle is
      another important pathophysiologic mechanism of TF onset. Through this
      hypothesis, this paper interprets the development and progression of TF.
      Moreover, the vicious circle may be universal, underlying the development of
      inflammation and fibrosis in various organs and tissues. The hypothesis also
      suggests a potential therapy strategy for the inhibition of fibrosis. 

PMID- 24731511
TI  - Absenteeism among medical and health science undergraduate students at Hawassa
      University, Ethiopia.
AB  - BACKGROUND: Student absenteeism is a major concern for university education
      worldwide. This study was conducted to determine the prevalence and causes of
      absenteeism among undergraduate medical and health sciences students at Hawassa
      University. METHODS: We conducted a cross-sectional study using a pretested self
      administered structured questionnaire from May-June 2013. The primary outcome
      indicator was self-reported absenteeism from lectures in the semester preceding
      the study period. The study included all regular undergraduate students who were
      enrolled in the University for at least one semester. The data was entered and
      analyzed using SPSS version 20. The association between class absenteeism and
      socio-demographic and behavioral correlates of absenteeism was determined by
      bivariate and multivariate analyses. Results were reported as crude odds ratios
      (COR), adjusted odds ratios (AOR) and 95% confidence intervals (CI). RESULTS:
      1200 students consented and filled the questionnaire. Of these students, 43.7%
      had missed three or more lectures and 14.1% (95% CI = 12.2-16.2) missed more than
      8 lectures in the preceding semester. There was a significant association between
      missing more than 8 lectures and age of students, chosen discipline (medicine),
      and social drug use. The main reasons reported for missing lectures were
      preparing for another examination, lack of interest, lecturer's teaching style,
      and availability of lecture material. CONCLUSION: At Hawassa University College
      of Medicine and Health Science student habits and teacher performance play a role
      in absenteeism from lectures. A university culture that promotes discipline and
      integrity especially among medical and older students discourages social drug use
      will likely improve motivation and attendance. Training in teaching methodologies
      to improve the quality and delivery of lectures should also help increase
      attendance.

PMID- 24731512
TI  - The Randomised Clinical Trial and the Hazard Ratio - medical research's Emperor's
      New Clothes?
AB  - As the enthusiasm for individualized treatment and targeted therapies continues
      to gain momentum, it seems timely to re-assess whether our current research tools
      are fit for purpose. Randomized Clinical Trials compare groups of patients, the
      Hazard Ratio is a 'group summary statistic', and modeling shows that the same
      Hazard Ratio score could result from a number of scenarios. Thus the current
      tools do not provide definitive information as to how to treat an individual
      patient. We therefore need to concentrate on the use of predictive factor
      analyses to identify the characteristics of subgroups of patients who respond to
      specific treatments. 

PMID- 24731513
TI  - Introduction: Invertebrate neuropeptides XIV.

PMID- 24731514
TI  - Changes to the school food and physical activity environment after guideline
      implementation in British Columbia, Canada.
AB  - BACKGROUND: High rates of childhood obesity have generated interest among policy
      makers to improve the school food environment and increase students' levels of
      physical activity. The purpose of this study was to examine school-level changes
      associated with implementation of the Food and Beverage Sales in Schools (FBSS)
      and Daily Physical Activity (DPA) guidelines in British Columbia, Canada.
      METHODS: Elementary and middle/high school principals completed a survey on the
      school food and physical activity environment in 2007-08 (N=513) and 2011-12
      (N=490). Hierarchical mixed effects regression was used to examine changes in: 1)
      availability of food and beverages; 2) minutes per day of Physical Education
      (PE); 3) delivery method of PE; and 4) school community support. Models
      controlled for school enrollment and community type, education and income.
      RESULTS: After policy implementation was expected, more elementary schools
      provided access to fruits and vegetables and less to 100% fruit juice. Fewer
      middle/high schools provided access to sugar-sweetened beverages, French fries,
      baked goods, salty snacks and chocolate/candy. Schools were more likely to meet
      150 min/week of PE for grade 6 students, and offer more minutes of PE per week
      for grade 8 and 10 students including changes to PE delivery method. School
      community support for nutrition and physical activity policies increased over
      time. CONCLUSION: Positive changes to the school food environment occurred after
      schools were expected to implement the FBSS and DPA guidelines. Reported changes
      to the school environment are encouraging and provide support for guidelines and
      policies that focus on increasing healthy eating and physical activity in
      schools.

PMID- 24731515
TI  - Invasive radiologic management of hemodialysis fistulas: measuring flow with an
      endovascular catheter.
AB  - OBJECTIVES: To analyze the values of flow obtained with an endovascular catheter,
      and to determine whether they are more reliable than angiographic and clinical
      findings for planning and for determining the outcome of invasive radiologic
      treatment of hemodialysis fistulas, as well as to determine the safety of this
      technique during interventional radiology procedures. MATERIAL AND METHODS: We
      used endovascular catheters to measure flow in 341 vascular accesses for
      hemodialysis (162 [47.6%] distal fistulas, 132 [38.4%] humeral fistulas, and 47
      [14%] arteriovenous grafts) in 598 procedures (a total of 3,051 flow
      measurements). Dysfunction was most commonly due to high pressures and flow
      deficits. RESULTS: The catheter was used to measure the results of radiologic
      treatment in 419 (70%) cases and only to measure the control of flow in the
      hemodialysis access in 179 (30%) cases. In the cases where lesions of the access
      had been treated radiologically, the flow improved by a mean of 1,232ml/min. In 2
      (0.35%) cases, the tip of the catheter perforated the wall of the vein; this
      complication was resolved by inflating a low pressure balloon. CONCLUSIONS:
      Endovascular catheters are useful for measuring flow in invasive vascular
      radiology procedures for hemodialysis. In assessing the hemodynamic status of a
      vascular access, they are most helpful in determining whether stenosis is
      present.

PMID- 24731516
TI  - A protocol for a systematic review of the effectiveness of interventions to
      reduce exposure to lead through consumer products and drinking water.
AB  - BACKGROUND: The toxic heavy metal lead continues to be a leading environmental
      risk factor, with the number of attributable deaths having doubled between 1990
      and 2010. Although major sources of lead exposure, in particular lead in petrol,
      have been significantly reduced in recent decades, lead is still used in a wide
      range of processes and objects, with developing countries disproportionally
      affected. The objective of this systematic review is to assess the effectiveness
      of regulatory, environmental and educational interventions for reducing blood
      lead levels and associated health outcomes in children, pregnant women and the
      general population. METHODS/DESIGN: The databases MEDLINE, Embase and the Global
      Health Library (GHL) will be searched using a sensitive search strategy. Studies
      in English, German, French, Spanish, Italian or Afrikaans will be screened
      according to predefined inclusion and exclusion criteria. We will consider
      randomized and non-randomized studies accepted by the Cochrane Effective Practice
      and Organization of Care (EPOC) Group, as well as additional non-randomized
      studies. Screening of titles and abstracts will be performed by one author. Full
      texts of potentially relevant studies will be independently assessed for
      eligibility by two authors. A single author will extract data, with a second
      reviewer checking the extraction form. Risk of bias will be assessed by two
      researchers using the Graphical Appraisal Tool for Epidemiological studies, as
      modified by the Centre for Public Health at the UK National Institute for Health
      and Care Excellence. Any inconsistencies in the assessment of eligibility, data
      extraction or quality appraisal will be resolved through discussion. Where two or
      more studies report the primary outcome blood lead levels within the same
      population group, intervention category and source of lead exposure, data will be
      pooled using random effects meta-analysis. In parallel, harvest plots as a
      graphical method of evidence synthesis will be used to present findings for blood
      lead levels and secondary outcomes. DISCUSSION: This systematic review will fill
      an important evidence gap with respect to the effectiveness of interventions to
      reduce lead in consumer products and drinking water in the context of new WHO
      guidelines for the prevention and management of lead poisoning. It will also
      contribute to setting a future research agenda.

PMID- 24731517
TI  - Hippocampal perivascular spaces are related to aging and blood pressure but not
      to cognition.
AB  - The risk factors of hippocampal dilated perivascular spaces (H-dPVS), their
      radiological relevance and their impact on cognitive performance remain under
      investigation. These aspects were evaluated in 1818 stroke- and dementia-free
      participants enrolled in the 3C-Dijon MRI study, using logistic regression,
      multiple linear regression, and Cox models. At study entry, the load of H-dPVS
      was found strongly associated with age and hypertension (degree 2 vs. degree 0:
      odds ratio: 1.16; 95% confidence interval: 1.02-1.33 and odds ratio: 1.98; 95%
      confidence interval: 1.39-2.81, respectively) and positively related to the
      presence of lacunar infarcts, white-matter hyperintensities volume, and
      hippocampal volume (p <= 0.024). Load of H-dPVS was not related to baseline
      cognitive performance (p > 0.05). Cox regression modeling did not show a
      significant relationship between the load of H-dPVS and incident dementia risk (p
      > 0.05). The present results support that both aging and blood pressure do play a
      key role in the development of H-dPVS in the older population. In contrast with
      the dilated perivascular spaces located in white matter or basal ganglia, the
      load of H-dPVS does not appear associated with occurrence of dementia.

PMID- 24731518
TI  - CHRNB3 c.-57A>G functional promoter change affects Parkinson's disease and
      smoking.
AB  - Cigarette smoking is protective in Parkinson's disease (PD), possibly because of
      nicotine action on brain nicotinic-acetylcholine receptors. The beta3 nicotinic
      acetylcholine receptor subunit (encoded by CHRNB3) is depleted in the striatum of
      PD patients and associated with nicotine dependence. Herein, the CHRNB3 gene was
      sequenced, and the c.-57G allele frequency was 0.31 and 0.26 among patients (n =
      596) and controls (n = 369), respectively (p = 0.02, odds ratio = 1.33, 95%
      confidence interval = 1.03-1.73). The c.-57G allele was strongly associated with
      smoking in patients, as 48.4% of c.-57G carriers compared with 32.6% of
      noncarriers reported smoking history (p < 0.0001). The transcription factor Oct-1
      binding was almost eliminated in lymphoblasts with the c.-57G/G genotype, to only
      6.5% percent, and the CHRNB3 promoter activity was reduced in cells with the c.
      57G/G genotype by 96%-70%. These findings suggest that the CHRNB3 c.-57A>G
      alteration affects the promoter activity and is associated with PD and smoking in
      PD patients. It is therefore possible that nicotine may be valuable for patients
      who carry this alteration and beneficial in PD only for patients with specific
      genotypes.

PMID- 24731519
TI  - Psychotic Alzheimer's disease is associated with gender-specific tau
      phosphorylation abnormalities.
AB  - Converging evidence suggests that psychotic Alzheimer's disease (AD + P) is
      associated with an acceleration of frontal degeneration, with tau pathology
      playing a primary role. Previous histopathologic and biomarker studies have
      specifically implicated tau pathology in this condition. To precisely quantify
      tau abnormalities in the frontal cortex in AD + P, we used a sensitive
      biochemical assay of total tau and 4 epitopes of phospho-tau relevant in AD
      pathology in a postmortem sample of AD + P and AD - P. Samples of superior
      frontal gyrus from 26 AD subjects without psychosis and 45 AD + P subjects with
      psychosis were analyzed. Results of enzyme-linked immunosorbent assay demonstrate
      that AD + P females, but not males, had significantly higher levels of
      phosphorylated tau in the frontal cortex. In males, but not females, AD + P was
      associated with the presence of alpha-synuclein pathology. These results support
      a gender dissociation of pathology in AD + P. The design of future studies aimed
      at the elucidation of cognitive and/or functional outcomes; regional brain
      metabolic deficits; or genetic correlates of AD + P should take gender into
      consideration.

PMID- 24731520
TI  - A cohort study of a tailored web intervention for preconception care.
AB  - BACKGROUND: Preconception care may be an efficacious tool to reduce risk factors
      for adverse pregnancy outcomes that are associated with lifestyles and health
      status before pregnancy. We conducted a web-based cohort study in Italian women
      planning a pregnancy to assess whether a tailored web intervention may change
      knowledge and behaviours associated with risks for adverse pregnancy outcomes.
      METHODS: The study was entirely conducted on the web on a cohort of Italian women
      of childbearing age. Data collected at baseline on health status, lifestyles and
      knowledge of risk factors for adverse pregnancy outcomes were used for generating
      a tailored document including recommendations for folic acid supplementation,
      obesity and underweight, smoking, alcohol consumption, vaccinations, chronic and
      genetic diseases, exposure to medications. Prevalence of risk factors and
      knowledge was assessed 6 months after the intervention. Logistic regression
      models were used to explore the factors associated with risk factors after the
      intervention. RESULTS: Of the 508 enrolled women, 282 (55.5%) completed the study
      after 6 months since the delivery of tailored recommendations. At baseline, 48%
      of the participants took folic acid supplementation (95% CI 43.2; 51.9) and 69%
      consumed alcohol (95% CI 64.7; 72.9). At the follow up 71% of the participants
      had a preconception visit with a physician. Moreover we observed a decrease of
      alcohol consumption (-46.5% 95% CI -53.28; -38.75) and of the proportion of women
      not taking folic acid supplementation (-23.4% 95% CI -31.0; 15.36). We observed
      an improvement in knowledge of the information about the preconception behaviours
      to prevent adverse pregnancy outcomes (20.9% 95% CI 14.6%; 27.1%). Having a
      preconception visit during follow up was significally associated to an increase
      in folic acid supplementation (OR 2.53 95% CI 1.40; 4.60). CONCLUSIONS: Our
      results suggest that a tailored web intervention may improve general
      preconception health in women planning a pregnancy. A web preconception
      intervention may be integrated with classic preconception care by health
      professionals. Clinical trials should be conducted to confirm these findings.

PMID- 24731522
TI  - Assets, challenges, opportunities: an Academy top ten.

PMID- 24731521
TI  - The 3Mg trial: a randomised controlled trial of intravenous or nebulised
      magnesium sulphate versus placebo in adults with acute severe asthma.
AB  - BACKGROUND: Magnesium sulphate, administered by the intravenous (i.v.) or inhaled
      (nebulised) route, has been proposed as a treatment for adults with acute severe
      asthma. Existing trials show mixed results and uncertain evidence of benefit.
      OBJECTIVES: We aimed to determine whether i.v. or nebulised magnesium sulphate
      improves symptoms of breathlessness and reduces the need for hospital admission
      in adults with acute severe asthma. DESIGN: Multicentre, double-blind, placebo
      controlled, three-arm, randomised trial. SETTING: The emergency departments of 34
      acute hospitals in the UK. PARTICIPANTS: We recruited 1109 adults (age >16 years)
      with acute severe asthma [peak expiratory flow rate (PEFR) <50% of
      best/predicted, respiratory rate >25 breaths per minute, heart rate >110 beats
      per minute or inability to complete sentences in one breath]. Patients with life
      threatening features or a contraindication to either nebulised or intravenous
      magnesium sulphate were excluded. INTERVENTIONS: Participants were randomly
      allocated to i.v. magnesium sulphate (2 g over 20 minutes) or nebulised magnesium
      sulphate (3 * 500 mg over 1 hour) or standard therapy alone. MAIN OUTCOME
      MEASURES: The primary outcome was the proportion of patients admitted to hospital
      (either after emergency department treatment or at any time over the subsequent 7
      days) and breathlessness measured on a 100-mm visual analogue scale (VAS) over 2
      hours after initiation of treatment. RESULTS: We randomised 406 patients to i.v.
      magnesium sulphate, 339 to nebulised magnesium sulphate and 364 to placebo.
      Hospital admission was recorded for 394, 332 and 358 patients, respectively, and
      VAS breathlessness for 357, 296 and 323 patients respectively. Mean age was 36.1
      years and 763 out of 1084 (70%) patients were female. Intravenous magnesium
      sulphate was associated with an odds ratio (OR) of 0.73 [95% confidence interval
      (CI) 0.51 to 1.04; p=0.083] for hospital admission, an improvement in VAS
      breathlessness that was 2.6 mm (95% CI -1.6 to 6.8 mm; p=0.231) greater than that
      associated with placebo and an improvement in PEFR that was 2.4 l/minute (95% CI 
      8.8 to 13.6 l/minute; p=0.680) greater than that associated with placebo.
      Nebulised magnesium sulphate was associated with an OR of 0.96 (95% CI 0.65 to
      1.40; p=0.819) for hospital admission, an improvement in VAS breathlessness that
      was 2.6 mm (95% CI -1.8 mm to 7.0 mm; p=0.253) less than that associated with
      placebo and an improvement in PEFR that was 2.6 l/minute (95% CI -9.2 to 14.5
      l/minute; p=0.644) less than that associated with placebo. There were no
      significant differences between i.v. or nebulised magnesium sulphate and placebo
      for any other outcomes. The number (%) of patients reporting any side effect was
      61 (15.5%) in the i.v. group, 52 (15.7%) in the nebuliser group and 36 (10.1%) in
      the placebo group. The ORs for suffering any side effect were 1.68 (95% CI 1.07
      to 2.63; p=0.025) for i.v. compared with placebo and 1.67 (95% CI 1.05 to 2.66;
      p=0.031) for nebuliser compared with placebo. CONCLUSIONS: We were unable to
      demonstrate a clinically worthwhile benefit from magnesium sulphate in acute
      severe asthma. There was some weak evidence of an effect of i.v. magnesium
      sulphate on hospital admission, but no evidence of an effect on VAS
      breathlessness or PEFR compared with placebo. We found no evidence that nebulised
      magnesium sulphate was more effective than placebo. TRIAL REGISTRATION: Current
      Controlled Trials ISRCTN04417063.

PMID- 24731523
TI  - MyPlate myths debunked.

PMID- 24731524
TI  - Learning to lead: developing dietetics leaders.

PMID- 24731525
TI  - How can registered dietitian nutritionists use health coaching techniques?

PMID- 24731526
TI  - Advances in uro-oncology "OncoForum": the best of 2013.
AB  - OBJECTIVE: To present the new findings in oncologic urology with impact on
      clinical practice which were displayed at 2013 major annual meetings (EAU, ESTRO,
      AUA, ASCO and ASTRO). METHODS: The abstracts on prostate kidney, bladder and
      upper tract urothelial cancer with the highest scores by the OncoForum committee,
      presented in 1013 Congresses are included in this paper. RESULTS: the following
      messages were considered as important by the OncoUrology Forum committee. In
      renal tumors T1a, comorbidities should be evaluated by its impact on overall and
      specific cancer survival, especially in men over 65. In metastatic renal tumors,
      the benefit of Everolimus vs. Sunitinib has not been demonstrated. Patients with
      non-muscle invasive bladder cancer of high risk, with three or more risk factors,
      should be considered for radical cystectomy. The ERSPC study' data demonstrate
      the benefit of the systematic screening in prostate cancer. In metastatic
      disease, the results of the Ra-223 and enzalutamide studies show benefit in pain
      control and overall survival in metastatic disease. CONCLUSIONS: Localized renal
      and non-muscle invasive bladder of high-risk tumors, should be assessed according
      to comorbidities or oncologic risk factors, to determinate the adequate treatment
      options. New data from metastatic prostate cancer clinical trials have shown
      promising results in the control of the disease.

PMID- 24731527
TI  - Adult onset methylphenidate induced dyskinesia after stroke.

PMID- 24731528
TI  - Evaluation of brain iron content in idiopathic REM sleep behavior disorder using
      quantitative magnetic resonance imaging.
AB  - BACKGROUND: Neuroimaging studies in patients with idiopathic rapid eye movement
      sleep behavior disorder (iRBD) show similar structural and functional changes to
      alpha-synucleinopathies, including PD. Until now, there have been few attempts to
      characterize brain iron deposition in iRBD. The aim of this study was to
      investigate brain iron content in patients with iRBD using quantitative magnetic
      resonance imaging (MRI). METHODS: 3-T MRI was performed in 15 patients with iRBD
      and 20 age-matched healthy control subjects. In order to evaluate the iron
      related neurodegenerative changes, we assessed volume and transverse relaxation
      rate (R2*) simultaneously. We used both region-based and voxel-based analysis.
      RESULTS: No significant differences in R2* values were found between iRBD groups
      and healthy control subjects. There were no areas of significantly reduced or
      increased gray matter and white matter volume in the iRBD group. Instead, lateral
      ventricle volumes measured automatically by FreeSurfer were significantly larger
      in patients with iRBD than in healthy controls (P < 0.05). CONCLUSION: The
      present study suggests that iron-related R2* values may not be an imaging
      biomarker for neurodegeneration in iRBD.

PMID- 24731529
TI  - Interleukin-6 dynamics as a basis for an early-warning monitor for sepsis and
      inflammation in individual pigs.
AB  - Static interleukin-6 (IL-6) levels of pigs contain considerable individual
      differences, which obstruct the practical use of IL-6 for disease monitoring
      purposes. It was hypothesised that interleukin-6 (IL-6) dynamics could be used to
      quantify these individual differences and carries critical information of the
      individual pig infection status. Time series of IL-6 responses in 25 pigs were
      analysed before and after infection by Actinobacillus pleuropneumoniae. The
      results indicated that amplitude increases of IL-6 fluctuations of individual
      pigs rather than static IL-6 values should be used as indicator of the infection
      state. This study shows the added value for IL-6 time series analyses of
      individual pigs. These results are a first step towards the development of
      objective individualised methods for monitoring and early detection of sepsis and
      inflammation processes in pigs by integrating animal response dynamics.

PMID- 24731530
TI  - Homogeneity of VacJ outer membrane lipoproteins among Pasteurella multocida
      strains and heterogeneity among members of Pasteurellaceae.
AB  - Outer membrane lipoproteins are widely distributed in Gram-negative bacteria
      which are involved in diverse mechanisms of physiology/pathogenesis. Various
      pathogenic bacterial strains belonging to the family-Pasteurellaceae have several
      surface exposed virulence factors including VacJ/VacJ-like lipoproteins. In the
      present study, vacJ gene encoding for VacJ outer membrane lipoprotein of
      different Pasteurella multocida strains (n = 10) were amplified, sequenced and
      compared with available VacJ/VacJ-like sequences (n = 45) of Pasteurellaceae
      members. Comparative multiple sequence analysis at amino acid level indicated
      absolute homogeneity of VacJ lipoprotein among different P. multocida strains.
      However, heterogeneity (18.0-89.9%) of VacJ lipoprotein was noticed among members
      of Pasteurellaceae. A predicted lipobox motif (L-3-[A/S/T/V]-2-[G/A]-1-C) was
      found to be conserved between 12-32aa residues at N-terminus among all VacJ
      sequences. Bioinformatic analysis indicated that VacJ is a chromosomal gene
      product exposed on the bacterial surface, possibly essential for either
      physiological or pathogenicity process of Pasteurellae and distributed widely
      among P. multocida serogroups. The study indicated potential possibilities of
      using absolutely conserved VacJ lipoprotein either as 'signature gene/protein' in
      developing diagnostic assay or as a recombinant subunit vaccine for P. multocida
      infections in livestock.

PMID- 24731531
TI  - Effect of tea tree oil (Melaleuca alternifolia) on the longevity and immune
      response of rats infected by Trypanosoma evansi.
AB  - This study aimed to evaluate the effect of tea tree oil (TTO - Melaleuca
      alternifolia) on hepatic and renal functions, and the immune response of rats
      infected by Trypanosoma evansi. A pilot study has shown that rats treated with
      TTO orally (1 ml kg(-1)) had increased survival rate without curative effect. In
      order to verify if increased longevity was related to a better immune response
      against T. evansi when using tea tree oil, a second experiment was conducted.
      Thus, twenty-four rats were divided into four groups. The groups A and B were
      composed of uninfected animals, and the groups C and D had rats experimentally
      infected by T. evansi. Animals from the groups B and D were treated orally with
      TTO (1 ml kg(-1)) for three days. Blood samples were collected to verify humoral
      response analysis for immunoglobulins (IgA, IgM, IgE, and IgG) and cytokines (TNF
      alpha, INF-gamma, IL-1, IL-6, IL-4, and IL-10) at days 0, 3, 5 and 15 post
      infection (PI). TTO treatment caused changes in the immunoglobulins and cytokines
      profile, as well as the course of T. evansi infection in rats. It was found that
      the TTO was not toxic, i.e., hepatic and renal functions were not affected.
      Therefore, it is possible to conclude that TTO influences the levels of
      inflammatory mediators and has trypanocidal effect, increasing life expectancy of
      rats infected by T. evansi.

PMID- 24731532
TI  - Pathology of bovine tuberculosis.
AB  - Bovine tuberculosis (bTB) is a chronic granulomatous caseous-necrotising
      inflammatory process that mainly affects the lungs and their draining lymph nodes
      (Ln.). The pathological changes associated with bTB infection reflect the
      interplay between the host defence mechanisms and the mycobacterial virulence
      factors and the balance between the immunologic protective responses and the
      damaging inflammatory processes. Inhalation is the most common infection route
      and causes lesions of the nasopharynx and lower respiratory tract, including its
      associated lymph nodes. The initial infection (primary complex) may be followed
      by chronic (post-primary) tuberculosis or may be generalised. Goat tuberculosis
      often produces liquefactive necrosis and caverns, similarly to human TB. The
      assessment of the severity of TB lesions is crucial for vaccine trials. Semi
      quantitative gross lesion scoring systems have been developed for cattle, but
      imaging technology has allowed the development of more standardised, objective,
      and quantitative methods, such as multi-detector computed tomography (MDCT),
      which provides quantitative measures of lesion volume.

PMID- 24731533
TI  - The cost-effectiveness of the Argus II retinal prosthesis in Retinitis Pigmentosa
      patients.
AB  - BACKGROUND: Retinitis Pigmentosa (RP) is a hereditary genetic disease causing
      bilateral retinal degeneration. RP is a leading cause of blindness resulting in
      incurable visual impairment and drastic reduction in the Quality of life of the
      patients. Second Sight Medical Products Inc. developed Argus II, a retinal
      prosthesis system for treating RP. Argus II is the world's first ever-commercial
      implant intended to restore some vision in the blind patients. The objective of
      this study was to assess the cost-effectiveness of the Argus(r) II Retinal
      Prosthesis System (Argus II) in Retinitis Pigmentosa (RP) patients. METHOD: A
      multi -state transition Markov model was developed to determine the cost
      effectiveness of Argus II versus usual care in RP from the perspective of
      healthcare payer. A hypothetical cohort of 1000 RP patients aged 46 years
      followed up over a (lifetime) 25-year time horizon. Health outcomes were
      expressed as quality adjusted life years (QALYs) and direct healthcare costs
      expressed in 2012 ?. Results are reported as incremental cost per ratios (ICERs)
      with outcomes and costs discounted at an annual rate of 3.5%. RESULTS: The ICER
      for Argus II was ?14,603/QALY. Taking into account the uncertainty in model
      inputs the ICER was ?14,482/QALY in the probabilistic analysis. In the scenarios
      of an assumption of no reduction on cost across model visual acuity states or a
      model time horizon as short as 10 years the ICER increased to ?31,890/QALY and
      ?49,769/QALY respectively. CONCLUSION: This economic evaluation shows that Argus
      II is a cost-effective intervention compared to usual care of the RP patients.
      The lifetime analysis ICER for Argus II falls below the published societal
      willingness to pay of EuroZone countries.

PMID- 24731534
TI  - A multicenter study on Leigh syndrome: disease course and predictors of survival.
AB  - BACKGROUND: Leigh syndrome is a progressive neurodegenerative disorder,
      associated with primary or secondary dysfunction of the mitochondrial oxidative
      phosphorylation. Despite the fact that Leigh syndrome is the most common
      phenotype of mitochondrial disorders in children, longitudinal natural history
      data is missing. This study was undertaken to assess the phenotypic and genotypic
      spectrum of patients with Leigh syndrome, characterise the clinical course and
      identify predictors of survival in a large cohort of patients. METHODS: This is a
      retrospective study of patients with Leigh syndrome that have been followed at
      eight centers specialising in mitochondrial diseases in Europe; Gothenburg,
      Rotterdam, Helsinki, Copenhagen, Stockholm, Brussels, Bergen and Oulu. RESULTS: A
      total of 130 patients were included (78 males; 52 females), of whom 77 patients
      had identified pathogenic mutations. The median age of disease onset was 7
      months, with 80.8% of patients presenting by the age of 2 years. The most common
      clinical features were abnormal motor findings, followed by abnormal ocular
      findings. Epileptic seizures were reported in 40% of patients. Approximately 44%
      of patients experienced acute exacerbations requiring hospitalisation during the
      previous year, mainly due to infections. The presence of pathological signs at
      birth and a history of epileptic seizures were associated with higher occurrence
      of acute exacerbations and/or relapses. Increased lactate in the cerebrospinal
      fluid was significantly correlated to a more severe disease course, characterised
      by early onset before 6 months of age, acute exacerbations and/or relapses, as
      well as brainstem involvement. 39% of patients had died by the age of 21 years,
      at a median age of 2.4 years. Disease onset before 6 months of age, failure to
      thrive, brainstem lesions on neuroimaging and intensive care treatment were
      significantly associated with poorer survival. CONCLUSIONS: This is a multicenter
      study performed in a large cohort of patients with Leigh syndrome. Our data help
      define the natural history of Leigh syndrome and identify novel predictors of
      disease severity and long-term prognosis.

PMID- 24731535
TI  - Multidisciplinary diabetes care with and without bariatric surgery in overweight
      people: a randomised controlled trial.
AB  - BACKGROUND: Bariatric surgery improves glycaemia in obese people with type 2
      diabetes, but its effects are uncertain in overweight people with this disease.
      We aimed to identify whether laparoscopic adjustable gastric band surgery can
      improve glucose control in people with type 2 diabetes who were overweight but
      not obese. METHODS: We did an open-label, parallel-group, randomised controlled
      trial between Nov 1, 2009, and June 30, 2013, at one centre in Melbourne,
      Australia. Patients aged 18-65 years with type 2 diabetes and a BMI between 25
      and 30 kg/m2 were randomly assigned (1:1), by computer-generated random sequence,
      to receive either multidisciplinary diabetes care plus laparoscopic adjustable
      gastric band surgery or multidisciplinary diabetes care alone. The primary
      outcome was diabetes remission 2 years after randomisation, defined as glucose
      concentrations of less than 7.0 mmol/L when fasting and less than 11.1 mmol/L 2 h
      after 75 g oral glucose, at least two days after stopping glucose-lowering drugs.
      Analysis was by intention to treat. This trial is registered with the Australian
      New Zealand Clinical Trials Registry, number ACTRN12609000286246. FINDINGS: 51
      patients were randomised to the multidisciplinary care plus gastric band group
      (n=25) or the multidisciplinary care only group (n=26), of whom 23 participants
      and 25 participants, respectively, completed follow-up to 2 years. 12 (52%)
      participants in the multidisciplinary care plus gastric band group and two (8%)
      participants in the multidisciplinary care only group achieved diabetes remission
      (difference in proportions 0.44, 95% CI 0.17-0.71; p=0.0012). One (4%)
      participant in the gastric band group needed revisional surgery and four others
      (17%) had a total of five episodes of food intolerance due to excessive
      adjustment of the band. INTERPRETATION: When added to multidisciplinary care,
      laparoscopic adjustable gastric band surgery for overweight people with type 2
      diabetes improves glycaemic control with an acceptable adverse event profile.
      Laparoscopic adjustable gastric band surgery is a reasonable treatment option for
      this population. FUNDING: Monash University Centre for Obesity Research and
      Education and Allergan.

PMID- 24731536
TI  - The metabolic burden of sleep loss.
AB  - In parallel with the increasing prevalence of obesity and type 2 diabetes, sleep
      loss has become common in modern societies. An increasing number of
      epidemiological studies show an association between short sleep duration, sleep
      disturbances, and circadian desynchronisation of sleep with adverse metabolic
      traits, in particular obesity and type 2 diabetes. Furthermore, experimental
      studies point to distinct mechanisms by which insufficient sleep adversely
      affects metabolic health. Changes in the activity of neuroendocrine systems seem
      to be major mediators of the detrimental metabolic effects of insufficient sleep,
      through favouring neurobehavioural outcomes such as increased appetite, enhanced
      sensitivity to food stimuli, and, ultimately, a surplus in energy intake. The
      effect of curtailed sleep on physical activity and energy expenditure is less
      clear, but changes are unlikely to outweigh increases in food intake. Although
      long-term interventional studies proving a cause and effect association are still
      scarce, sleep loss seems to be an appealing target for the prevention, and
      probably treatment, of metabolic disease.

PMID- 24731537
TI  - Evaluation of the Cochrane Collaboration's tool for assessing the risk of bias in
      randomized trials: focus groups, online survey, proposed recommendations and
      their implementation.
AB  - BACKGROUND: In 2008, the Cochrane Collaboration introduced a tool for assessing
      the risk of bias in clinical trials included in Cochrane reviews. The risk of
      bias (RoB) tool is based on narrative descriptions of evidence-based
      methodological features known to increase the risk of bias in trials. METHODS: To
      assess the usability of this tool, we conducted an evaluation by means of focus
      groups, online surveys and a face-to-face meeting. We obtained feedback from a
      range of stakeholders within The Cochrane Collaboration regarding their
      experiences with, and perceptions of, the RoB tool and associated guidance
      materials. We then assessed this feedback in a face-to-face meeting of experts
      and stakeholders and made recommendations for improvements and further
      developments of the RoB tool. RESULTS: The survey attracted 380 responses.
      Respondents reported taking an average of between 10 and 60 minutes per study to
      complete their RoB assessments, which 83% deemed acceptable. Most respondents
      (87% of authors and 95% of editorial staff) thought RoB assessments were an
      improvement over past approaches to trial quality assessment. Most authors liked
      the standardized approach (81%) and the ability to provide quotes to support
      judgements (74%). A third of participants disliked the increased workload and
      found the wording describing RoB judgements confusing. The RoB domains reported
      to be the most difficult to assess were incomplete outcome data and selective
      reporting of outcomes. Authors expressed the need for more guidance on how to
      incorporate RoB assessments into meta-analyses and review conclusions. Based on
      this evaluation, recommendations were made for improvements to the RoB tool and
      the associated guidance. The implementation of these recommendations is currently
      underway. CONCLUSIONS: Overall, respondents identified positive experiences and
      perceptions of the RoB tool. Revisions of the tool and associated guidance made
      in response to this evaluation, and improved provision of training, may improve
      implementation.

PMID- 24731538
TI  - Development of the Addiction Dimensions for Assessment and Personalised Treatment
      (ADAPT).
AB  - BACKGROUND: Convergent research reveals heterogeneity in substance use disorders
      (SUD). The Addiction Dimensions for Assessment and Personalised Treatment (ADAPT)
      is designed to help clinicians tailor therapies. METHODS: Multicentre study in 21
      SUD clinics in London, Birmingham (England) and Adelaide (Australia). 132
      clinicians rated their caseload on a beta version with 16 ordinal indicators of
      addiction severity, health and social problem complexity, and recovery strengths
      constructs. In Birmingham, two in-treatment outcomes were recorded after 15
      months: 28-day drug use (Treatment Outcome Profile; n=703) and Global Assessment
      of Functioning (GAF; DSM-IV Axis V; n=695). Following item-level screening (inter
      rater reliability [IRR]; n=388), exploratory structural equation models (ESEM),
      latent profile analysis (LPA), and mixed-effects regression evaluated construct,
      concurrent and predictive validity characteristics, respectively. RESULTS: 2467
      patients rated (majority opioid or stimulant dependent, enrolled in opioid
      medication assisted or psychological treatment). IRR-screening removed two items
      and ESEM models identified and recalibrated remaining indicators (root mean
      square error of approximation 0.066 [90% confidence interval 0.055-0.064]).
      Following minor re-specification and satisfactory measurement invariance
      evaluation, ADAPT factor scores discriminated patients by sample, addiction
      therapy and drug use. LPA identified three patient sub-types: Class 1 (moderate
      severity, moderate complexity, high strengths profile; 46.9%); Class 2 (low
      severity, low complexity, high strengths; 25.4%) and Class 3 (high severity, high
      complexity, low strengths; 27.7%). Class 2 had higher GAF (z=4.30). Class 3
      predicted follow-up drug use (z=2.02) and lower GAF (z=3.51). CONCLUSION: The
      ADAPT is a valid instrument for SUD treatment planning, clinical review and
      outcome evaluation. Scoring and application are discussed.

PMID- 24731539
TI  - Unraveling human protein interaction networks underlying co-occurrences of
      diseases and pathological conditions.
AB  - BACKGROUND: Human diseases frequently cause complications such as obesity-induced
      diabetes and share numbers of pathological conditions, such as inflammation, by
      dysfunctions of common functional modules, such as protein-protein interactions
      (PPIs). METHODS: Our developed pipeline, ICod (Interaction analysis for disease
      Comorbidity), grades similarities between pairs of disease-related PPIs including
      comorbid diseases and pathological conditions. ICod displayed a disease
      similarity network consisting of nodes of disease PPIs and edges of similarity
      value. As a proof of concept, eight complex diseases and pathological conditions,
      such as type 2 diabetes, obesity, inflammation, and cancers, were examined to
      discover whether PPIs shared between diseases were associated with comorbidities.
      RESULTS: By comparing Medicare reports of disease co-occurrences from 31 million
      patients, the disease similarity network shows that PPIs of pathological
      conditions, including insulin resistance, and inflammation, overlap significantly
      with PPIs of various comorbid diseases, including diabetes, obesity, and cancers
      (p < 0.05). Interestingly, maintaining connectivity between essential genes was
      more drastically perturbed by removing a node of a disease-related gene rather
      than a pathological condition-related gene, such as one related to inflammations.
      CONCLUSION: Thus, PPIs of pathological symptoms are underlying functional modules
      across diseases accompanying comorbidity phenomena, whereas they contribute only
      marginally to maintaining interactions between essential genes.

PMID- 24731540
TI  - N(4)-Acyl derivatives as lipophilic prodrugs of cidofovir and its 5-azacytosine
      analogue, (S)-HPMP-5-azaC: chemistry and antiviral activity.
AB  - Even number fatty acid residues-docosanoyl (behenoyl) and stearoyl were selected
      for introduction to the N(4)-position of (S)-1-[3-hydroxy-2
      (phosphonomethoxy)propyl]cytosine) (HPMPC, cidofovir), and its 5-azacytosine
      counterpart, (S)-1-[3-hydroxy-2-(phosphonomethoxy)propyl]cytosine) (HPMP-5-azaC)
      with the aim to prepare a new type of lipophilic prodrugs. The study on the
      influence of these modifications to the stability and biological activity of both
      antivirals was performed. Different reactivity of both systems towards acylation
      reactions was also found: the 4-NH2 group of cidofovir was more reactive compared
      to that of HPMP-5-azaC. In 5-azacytosine derivatives, we found mostly a
      destabilizing effect of the N(4)-acylation but this could be compensated by a
      positive influence of the esterification of the phosphonate group. Chemical
      stability of the 5-azacytosine moiety in the HPMP series is increasing in the
      following order: HPMP-5-azaC<cyclic HPMP-5-azaC<HPMP-5-azaC esters. From the view
      of prodrug development, the best chemical stability was observed in case of the
      double prodrug 7: the N(4)-behenoyl derivative of the hexadecyloxyethyl ester of
      cyclic HPMP-5-azaC. The free phosphonic acid (N(4)-behenoyl-HPMPC) appeared to be
      a more potent and selective inhibitor of herpesvirus replication than the parent
      HPMPC derivative. 

PMID- 24731542
TI  - Medical emergency response in a sub-acute hospital: improving the model of care
      for deteriorating patients.
AB  - OBJECTIVE: To assess the frequency, characteristics and outcomes of medical
      emergency response (MER) calls in a sub-acute hospital setting. METHODS: The
      present study was a retrospective observational study in a sub-acute hospital
      providing aged care, palliative care, rehabilitation, veteran's mental health and
      elective surgical services. We assessed annual MER call numbers between 2005 and
      2011 in the context of contemporaneous changes to hospital services. We also
      assessed MER calls over a 12-month period in detail using standardised case
      report forms and the scanned medical record. RESULTS: There were 2285 multiday
      admissions in the study period where 141 MER calls were triggered in 132 patients
      (61.7 calls per 1000 admissions). The median patient age was 83.0 years, and
      55.3% of patients were men. Most calls occurred on weekdays and during the
      daytime, and were triggered by altered conscious state, low oxygen saturations
      and hypotension. Documentation of escalation of care before the MER call was not
      present in 99 of 141 (70.2%) calls. Following the call, in 70 of 141 (49.6%)
      cases, the patient was transferred to the acute campus, where 52 (74.2%) and 14
      (20%) patients required ward and intensive care level treatment, respectively.
      Thirty-seven of 132 (28%) patients died. A palliative care physician adjudicated
      that most of these patients who died (24/37; 64.9%) were appropriate for a call,
      but that 19 (51.4%) should have received palliation at the time of the call.
      Compared with survivors, patients who died after the MER call were more likely
      originally admitted from supported accommodation. CONCLUSIONS: MER calls in our
      sub-acute hospital occurred in elderly patients and are associated with an in
      hospital mortality of 28%. A small proportion of patients required intensive care
      level treatment. There is a need to improve processes involving escalation of
      care before MER call activation and to revise advance care directives. What is
      known about this topic? Rapid response team (RRT) activation has been well
      described in the acute hospital setting. Although the impact on survival benefit
      to patients remains controversial, it has been widely adopted as a model of care
      to respond to deteriorating ward patients. This is particularly relevant in
      Australia at present with the implementation of the new National Safety and
      Quality Health Service Standards. What does this paper add? There have not been
      any previous papers published on rapid response systems in a sub-acute hospital.
      This paper describes some of the changes and challenges associated with
      increasing RRT activations in a sub-acute health care facility. What are the
      implications for practitioners? For clinicians in a sub-acute setting, the study
      reinforces the importance of pre-emptively documenting and communicating advance
      care directives. In addition, it is important to identify patients with
      reversible pathology likely to benefit from transfer and acute care, and to avoid
      the transfer of those who will not and, instead, provide appropriate palliation.
      For practitioners involved in models of care for deteriorating patients, the
      study provides information on where problems occurred in our system and the
      strategies used to address these issues.

PMID- 24731543
TI  - [Design and piloting of a structured service medication dispensing process].
AB  - OBJECTIVE: The aim of this article is to design and pilot a protocol for the
      dispensing of medications service. DESIGN: Using the requirements proposed in the
      Ministry of Health Pharmaceutical Care Consensus, a literature search was made
      applying qualitative consensus techniques. An observational, cross-sectional
      study was conducted from March to June 2009. SETTING: A total of 53 community
      pharmacies from 24 Spanish counties. PARTICIPANT: Patients who requested one or
      more particular medications with or without medical prescription for their own
      use or for someone in their care. MAIN MEASUREMENTS: The personalised medication
      information (IPM), the problems associated with the medications (PRM), and the
      negative results associated with the medication (RNM), detected by the pharmacist
      each time medication was dispensed, as well as the perception of the pharmacist
      on the operability of the protocol were recorded. RESULTS: A total of 870
      medications were dispensed, with 423 (48.6%) cases of lack of personalised
      medication information (IPM) being detected. PRM were detected in 10.11% of the
      dispensed medications, as well as 68 (7.81%) suspected RNM: safety (n = 35;
      51.5%), effectiveness (n = 29; 42.6%) and necessity (n = 4; 5.8%). Almost two
      thirds (65.21%) of the pharmacists said that the protocol is in operation.
      CONCLUSIONS: The designed protocol helped to detect deficiencies in the
      information to the patients about their medications, as well as the PRM and RNM,
      and is shown to be tool that is easy to use and apply.

PMID- 24731541
TI  - The cannabinoid acids, analogs and endogenous counterparts.
AB  - The cannabinoid acids are a structurally heterogeneous group of compounds some of
      which are endogenous molecules and others that are metabolites of
      phytocannabinoids. The prototypic endogenous substance is N-arachidonoyl glycine
      (NAgly) that is closely related in structure to the cannabinoid agonist
      anandamide. The most studied phytocannabinoid is Delta(9)-THC-11-oic acid, the
      principal metabolite of Delta(9)-THC. Both types of acids have in common several
      biological actions such as low affinity for CB1 anti-inflammatory activity and
      analgesic properties. This suggests that there may be similarities in their
      mechanism of action, a point that is discussed in this review. Also presented are
      reports on analogs of the acids that provide opportunities for the development of
      novel therapeutic agents, such as ajulemic acid. 

PMID- 24731544
TI  - Solvent systems with n-hexane and/or cyclohexane in countercurrent chromatography
      -Physico-chemical parameters and their impact on the separation of alkyl
      hydroxybenzoates.
AB  - Countercurrent chromatography (CCC) is an efficient preparative separation
      technique based on the liquid-liquid distribution of compounds between two phases
      of a biphasic liquid system. The crucial parameter for the successful application
      is the selection of the solvent system. Especially for nonpolar analytes the
      selection options are limited. On the search for a suitable solvent system for
      the separation of an alkyl hydroxybenzoate homologous series, we noted that the
      substitution of cyclohexane with n-hexane was accompanied with unexpected
      differences in partitioning coefficients of the individual analytes. In this
      study, we investigated the influence of the subsequent substitution of n-hexane
      with cyclohexane in the n-hexane/cyclohexane/tert-butylmethylether/methanol/water
      solvent system family. Exact phase compositions and polarity, viscosity and
      density differences were determined to characterize the different mixtures
      containing n-hexane and/or cyclohexane. Findings were confirmed by performing CCC
      separations with different mixtures, which led to baseline resolution for
      positional isomers when increasing the amount of cyclohexane while the resolution
      between two pairs of structural isomers decreased. With the new methodology
      described, structurally similar compounds could be resolved by choosing a certain
      ratio of n-hexane to cyclohexane. 

PMID- 24731545
TI  - Hydrophilic modification gigaporous resins with poly(ethylenimine) for high
      throughput proteins ion-exchange chromatography.
AB  - High hydrophilicity of gigaporous microspheres based on a copolymer of
      poly(glycidyl methacrylate)-co-divinyl benzene (PGMA-DVB) was successfully
      realized through coating the branched polyethyleneimine (PEI) in PGMA-DVB
      microspheres. PEI with various molecules weights and different branching agents
      were identified in terms of protein recovery as evaluation approach. For this
      evaluation, PEI600 (Mw=600) and poly (ethylene glycol) diglycidyl ether (PEGDE,
      Mw=400) were used as modification agent and branching agent, respectively. The
      modified microspheres showed good permeability and revealed a certain mechanical
      strength. After modification, the protein recovery increased from 40% to >90%.
      The protein recovery increased with the branched generations and the first and
      second generations could give the protein recovery of 93% and 96%, respectively.
      Meanwhile, the ionic capacity also showed a rising trend in the range of 0.11
      0.32mmol/mL with the branched generations. But the dynamic binding capacity of
      protein (bovine serum albumin, BSA as the model protein) increased at first and
      then decreased. Analysis of the dry microspheres structure by mercury intrusion
      method as well as observation of the branched PEI on PGMA-DVB membrane in aqueous
      solution indicated that excess PEI chains with the extended state in the second
      generation would block the small pores and decrease the accessible surface area.
      Therefore, the protein capacity on the second generation, on the contrary, was
      lower than that on the first generation. Meanwhile, it was found that the PEI
      chains in the modified microspheres changed their construction from the extended
      to the collapsed state with increase of NaCl concentration. And the corresponding
      pore size of the modified microspheres increased with salt concentration through
      low-field nuclear magnetic resonance. Dynamic binding capacity of proteins on the
      modified supports did not significantly change with increase of the flow rate.
      The media showed good performance for separation three model proteins at high
      flow rate of 1084cm/h. This modified gigaporous microspheres had a large
      potential in application for rapid separation of biomolecules. 

PMID- 24731546
TI  - Pretreatment with buthionine sulfoximine enhanced uptake and retention of BSH in
      brain tumor.
AB  - To determine the influence of buthionine sulfoximine (BSO) on boron
      biodistribution after sulfhydryl borane (BSH) administration for boron neutron
      capture therapy, the effectiveness of the combination of BSO with sulfhydril-
      (BSH) and non-sulfhydril (B12H12 and BNH3) boron compounds, and the interval
      between BSO and BSH administration, the retention of boron in tissues have been
      evaluated using a 9L rat tumor model. Simultaneous administration of BSH and BSO
      showed significantly higher boron accumulation compared to that without BSO,
      however there was no difference in tissue boron level between B12H12 and BNH3
      administration with BSO or without BSO. The longer interval (6h) between BSH and
      BSO administration related to the highest boron concentration in the brain and
      subcutaneous tumors compared to shorter intervals (0.5, 3h). Boron concentration
      in subcutaneous and brain tumors was maintained for 6 and 12h after the
      administration of BSH following BSO pretreatment. 

PMID- 24731547
TI  - Factors associated with medication adherence and persistence of treatment for
      hypertension in a Medicaid population.
AB  - BACKGROUND: Non-adherence with antihypertensive therapy is a significant problem.
      Prior research has generally focused upon one drug or one drug class. Current
      information across multiple antihypertensive drug classes is limited. OBJECTIVES:
      To describe the initial treatment of recipients of Louisiana Medicaid with newly
      diagnosed hypertension; evaluate differences in adherence and persistence rates
      among multiple antihypertensive drug classes; and test the association of drug
      classes, race, gender, age and comorbidity with adherence and persistence to drug
      therapy. METHODS: In a retrospective analysis of administrative claims data,
      initial therapy was described by type and drug class for 4544 Medicaid recipients
      with newly-diagnosed hypertension. Recipients were placed into cohorts based upon
      drug classes (diuretics, beta-blockers, angiotensin-II receptor blockers,
      angiotensin converting enzyme inhibitors, and calcium channel blockers).
      Persistence with drug therapy and Medication Possession Ratios (MPR) were
      calculated for 6-month and 12-month periods following diagnosis. Drug class and
      demographic variables were used as predictor variables in logistic regression
      analyses of persistence and MPR. RESULTS: Recipients in the study group were
      primarily female (66%) and Black (65%). Recipients initially were treated with
      monotherapy (33%), multiple drugs (11%), fixed combinations (8%) or no drugs
      (48%). After one year, 62% of recipients were not receiving drug therapy.
      Persistence rates by cohort ranged from 26% to 42% at 6-months following
      diagnosis, and 14%-28% at 12-months. The proportion of recipients by cohort with
      MPRs of 0.8 or above ranged from 43% to 60% at 6-months and 25%-42% at 12-months.
      Race, comorbidities, and initial drug therapy were significant predictors of both
      persistence and MPR. CONCLUSIONS: Within this study group, adherence and
      persistence to medication therapy were less than optimal. Future efforts to
      improve compliance with medication therapy could be focused upon specific groups
      having poor adherence and/or persistence within the drug class cohorts analyzed
      in this study.

PMID- 24731548
TI  - Nurses' and care workers' experiences of spiritual needs in residents with
      dementia in nursing homes: a qualitative study.
AB  - BACKGROUND: The aim of the study was to investigate nurses' and care workers'
      experiences of spiritual needs among residents with dementia in nursing homes.
      Nurses claim to practice holistic nursing. Nevertheless, there is little
      knowledge about how to recognise spiritual needs in residents with dementia.
      METHODS: The study was conducted using a qualitative method with an exploratory
      design. Eight focus- group interviews in four Norwegian nursing homes were
      performed from June 2011 - Jan 2012. Using open-ended research questions, a total
      of 31 participants were asked to share their understanding and experiences
      regarding residents' spiritual needs. The interviews were analysed using a
      phenomenological - hermeneutical method. RESULTS: The nurses' and care workers'
      experiences of residents' spiritual needs were related to three main themes; i)
      The need for serenity and inner peace, described as "contemplative and restful
      moments" and "calmness due to familiarity", ii) The need for confirmation,
      described as "love and proximity" and iii) The need to express faith and beliefs,
      described as "participate in worship and prayers" and "approaching death". The
      comprehensive analyses revealed that the nurses believe the residents' spiritual
      needs were linked to the residents' previous sources of finding meaning, in
      relation to inter-personal, intra-personal and trans-personal dimensions in
      residents' lives. CONCLUSIONS: Nurses' and care workers' experiences of spiritual
      needs in people with dementia are very similar to the findings for the general
      population regardless of the severity of the dementia. The study's relevance to
      clinical practice indicates the importance of developing more knowledge about how
      people with dementia in nursing homes express spiritual needs and how to observe
      and interpret such needs.

PMID- 24731549
TI  - Possibility of graphene growth by close space sublimation.
AB  - Carbon films on the Si/SiO2 substrate are fabricated using modified method of
      close space sublimation at atmospheric pressure. The film properties have been
      characterized by micro-Raman and X-ray photoelectron spectroscopy and
      monochromatic ellipsometry methods. Ellipsometrical measurements demonstrated an
      increase of the silicon oxide film thickness in the course of manufacturing
      process. The XPS survey spectra of the as-prepared samples indicate that the main
      elements in the near-surface region are carbon, silicon, and oxygen. The narrow
      scan spectra of C1s, Si2p, O1s regions indicate that silicon and oxygen are
      mainly in the SiOx (x ~ 2) oxide form, whereas the main component of C1s spectrum
      at 284.4 eV comes from the sp2-hybridized carbon phase. Micro-Raman spectra
      confirmed the formation of graphene films with the number of layers that depended
      on the distance between the graphite source and substrate. 

PMID- 24731550
TI  - The Epstein Barr-encoded BART-6-3p microRNA affects regulation of cell growth and
      immuno response in Burkitt lymphoma.
AB  - BACKGROUND: Burkitt lymphoma is an aggressive B-cell lymphoma presenting in three
      clinical forms: endemic, sporadic and immunodeficiency-associated. More than 90%
      of endemic Burkitt lymphoma carry latent Epstein-Barr virus, whereas only 20% of
      sporadic Burkitt lymphoma are associated with Epstein-Barr infection. Although
      the Epstein-Barr virus is highly related with the endemic form, how and whether
      the virus participates in its pathogenesis remains to be fully elucidated. In
      particular, the virus may impair cellular gene expression by its own encoded
      microRNAs. METHODS: Using microRNA profiling we compared Epstein-Barr-positive
      and Epstein-Barr-negative Burkitt lymphoma cases for both cellular and viral
      microRNAs. The array results were validated by qRT-PCR, and potential targets of
      viral microRNAs were then searched by bioinformatic predictions, and classified
      in functional categories, according to the Gene Ontology. Our findings were
      validated by in vitro functional studies and by immunohistochemistry on a larger
      series of cases. RESULTS: We showed that a few cellular microRNAs are
      differentially expressed between Epstein-Barr-positive and Epstein-Barr-negative
      Burkitt lymphoma cases, and identified a subset of viral microRNAs expressed in
      Epstein-Barr-positive Burkitt lymphomas. Of these, we characterized the effects
      of viral BART6-3p on regulation of cellular genes. In particular, we analyzed the
      IL-6 receptor genes (IL-6Ralpha and IL-6ST), PTEN and WT1 expression for their
      possible relevance to Burkitt lymphoma. By means of immunohistochemistry, we
      observed a down-regulation of the IL-6 receptor and PTEN specifically in Epstein
      Barr-positive Burkitt lymphoma cases, which may result in the impairment of key
      cellular pathways and may contribute to malignant transformation. On the
      contrary, no differences were observed between Epstein-Barr-positive and Epstein
      Barr-negative Burkitt lymphoma cases for WT1 expression. CONCLUSIONS: Our
      preliminary results point at an active role for the Epstein-Barr virus in Burkitt
      lymphomagenesis and suggest new possible mechanisms used by the virus in
      determining dysregulation of the host cell physiology.

PMID- 24731551
TI  - [Functional neuroimaging in the diagnosis of patients with Parkinsonism: Update
      and recommendations for clinical use].
AB  - Functional Neuroimaging has been traditionally used in research for patients with
      different Parkinsonian syndromes. However, the emergence of commercial
      radiotracers together with the availability of single photon emission computed
      tomography (SPECT) and, more recently, positron emission tomography (PET) have
      made them available for clinical practice. Particularly, the development of
      clinical evidence achieved by functional neuroimaging techniques over the past
      two decades have motivated a progressive inclusion of several biomarkers in the
      clinical diagnostic criteria for neurodegenerative diseases that occur with
      Parkinsonism. However, the wide range of radiotracers designed to assess the
      involvement of different pathways in the neurodegenerative process underlying
      Parkinsonian syndromes (dopaminergic nigrostriatal pathway integrity, basal
      ganglia and cortical neuronal activity, myocardial sympathetic innervation), and
      the different neuroimaging techniques currently available (scintigraphy, SPECT
      and PET), have generated some controversy concerning the best neuroimaging test
      that should be indicated for the differential diagnosis of Parkinsonism. In this
      article, a panel of nuclear medicine and neurology experts has evaluated the
      functional neuroimaging techniques emphazising practical considerations related
      to the diagnosis of patients with uncertain origin parkinsonism and the
      assessment Parkinson's disease progression.

PMID- 24731552
TI  - Melatonin attenuates prenatal dexamethasone-induced blood pressure increase in a
      rat model.
AB  - Although antenatal corticosteroid is recommended to accelerate fetal lung
      maturation, prenatal dexamethasone exposure results in hypertension in the adult
      offspring. Since melatonin is a potent antioxidant and has been known to regulate
      blood pressure, we examined the beneficial effects of melatonin therapy in
      preventing prenatal dexamethasone-induced programmed hypertension. Male offspring
      of Sprague-Dawley rats were assigned to four groups (n = 12/group): control,
      dexamethasone (DEX), control + melatonin, and DEX + melatonin. Pregnant rats
      received intraperitoneal dexamethasone (0.1 mg/kg) from gestational day 16 to 22.
      In the melatonin-treatment groups, rats received 0.01% melatonin in drinking
      water during their entire pregnancy and lactation. Blood pressure was measured by
      an indirect tail-cuff method. Gene expression and protein levels were analyzed by
      real-time quantitative polymerase chain reaction and Western blotting,
      respectively. At 16 weeks of age, the DEX group developed hypertension, which was
      partly reversed by maternal melatonin therapy. Reduced nephron numbers due to
      prenatal dexamethasone exposure were prevented by melatonin therapy. Renal
      superoxide and NO levels were similar in all groups. Prenatal dexamethasone
      exposure led to increased mRNA expression of renin and prorenin receptor and up
      regulated histone deacetylase (HDAC)-1 expression in the kidneys of 4-month-old
      offspring. Maternal melatonin therapy augmented renal Mas protein levels in DEX +
      melatonin group, and increased renal mRNA expression of HDAC-1, HDAC-2, and HDAC
      8 in control and DEX offspring. Melatonin attenuated prenatal DEX-induced
      hypertension by restoring nephron numbers, altering RAS components, and
      modulating HDACs. 

PMID- 24731553
TI  - Establishment of spiroplasma-infected hemocytes as an in vitro laboratory culture
      model of Chinese mitten crab Eriocheir sinensis.
AB  - Spiroplasma is a novel pathogen of commercially exploited crustaceans. To more
      full clarify its pathogenic mechanism at the molecular level in vitro, a
      spiroplasma-infected hemocytes model was developed as described here, using a
      modified method of hemocytes culture from the Chinese mitten crab Eriocheir
      sinensis. It has been standardized by employing L-15 growth medium supplemented
      with 15% fetal bovine serum along with 0.15% glucose, 0.75% NaCl, antibiotics
      (100 U ml(-1) penicillin, 100 U ml(-1) streptomycin) and a suitable pH of 7.20
      7.40, incubated at 28 degrees C without the requirement for 5% carbon dioxide.
      Cytopathic effects of Spiroplasma eriocheiris in the cultures, including cell
      debris and cellular exudates, were observed as early as 36 h post-inoculation.
      The green fluorescent dye Alex-488 was used as an immunofluorescence marker of S.
      eriocheiris to study its adhesion to, and infection of, the host cell. At about
      24-h post-inoculation, a large number of spiroplasmas were observed infecting the
      host hemocytes cells, which became slug-like and widely distributed in the
      culture. Intracellular inclusion bodies containing spiroplasmas, and a large
      number of free spiroplasmas released from the ruptured cells, were observed using
      transmission electron microscopy. All the results show that S. eriocheiris can
      invade E. sinensis hemocytes in vitro, and this can provide a significant step
      forward toward further study of the relationship between the novel pathogen
      spiroplasma and its hosts in laboratory experimental studies.

PMID- 24731554
TI  - Pattern of childhood ocular morbidity in rural eye hospital, Central Ethiopia.
AB  - BACKGROUND: This study was aimed to determine the pattern of childhood eye
      disorders in patients attending outpatient eye department of a rural eye hospital
      in central Ethiopia. METHODS: A cross-sectional survey of ocular morbidity among
      children less than 15 years of age who presented at a rural eye hospital in
      central Ethiopia between August - October 2012 was conducted. Demographic data,
      visual acuity, source and type of injury, type of refractive errors and diagnosis
      were collected and analyzed using SPSS. A p value less than 0.05 was considered
      statistically significant. RESULT: A total of 735 children were examined in this
      study. The age range of the children varied from three months to 15 years of age.
      The mean (SD) age of the study population was 9.37 (4.95) years. 369 (50.2%) of
      the patients were females. The majority of cases were observed in older children
      (11-15 years) accounting for almost half of all the cases. The most common ocular
      morbidity encountered was conjunctivitis (35%), then ocular trauma (11.8%),
      refractive error (11.4%) and trachoma (7.6%). Bilateral visual impairment (UCVA <
      6/18 in the better eye) was found in 119 children, and the causes were refractive
      errors (47.1%), keratitis/corneal opacity (16%), amblyopia (14.3%), ocular trauma
      (11.8%), cataract (6.3%), Glaucoma (2%) and uveitis (2%). CONCLUSION: The three
      most common causes of childhood ocular morbidity in this study were
      conjunctivitis, ocular injuries and refractive errors. These disorders require
      attention of all the health professionals for proper management or early referral
      because they can lead to visual impairment and blindness. Health education is
      necessary for the prevention of childhood eye injuries, as well as early
      presentation of children to eye care centers for the treatment of eye disorders.

PMID- 24731555
TI  - Role of a Janus kinase 2-dependent signaling pathway in platelet activation.
AB  - INTRODUCTION: Janus kinases (JAKs) are intracellular non-receptor tyrosine
      kinases that transduce cytokine-mediated signals through a pathway mediated by
      JAK and the signal transducer and activator of transcription (STAT) proteins. The
      JAK-STAT pathway is involved in immune response, inflammation, and tumorigenesis.
      Platelets are anuclear blood cells that play a central role in hemostasis.
      METHODS: The aggregometry, immunoblotting, and platelet functional analysis used
      in this study. RESULTS: We found that the JAK2 inhibitor AG490 (25 and 50MUM)
      attenuated collagen-induced platelet aggregation and calcium mobilization in a
      concentration-dependent manner. In the presence of AG490, the phosphorylation of
      PLCgamma2, protein kinase C (PKC), Akt or JNK in collagen-activated aggregation
      of human platelets was also inhibited. In addition, we found that various
      inhibitors, such as the PLCgamma2 inhibitor U73122, the PKC inhibitor Ro318220,
      the phospoinositide 3-kinase inhibitor LY294002, the p38 mitogen-activated
      protein kinase inhibitor SB203580, the ERK inhibitor PD98059, and the JNK
      inhibitor SP600125, had no effects on collagen-induced JAK2 activity. However,
      U73122, Ro318220 and SP600125 significantly diminished collagen-induced STAT3
      phosphorylation. These findings suggest that PLCgamma2-PKC and JNK are involved
      in JAK2-STAT3 signaling in collagen-activated platelets. CONCLUSION: Our results
      demonstrate that the JAK2-STAT3 pathway is involved in collagen-induced platelet
      activation through the activation of JAK2-JNK/PKC-STAT3 signaling. The inhibition
      of JAK2 may represent a potential therapeutic strategy for the preventing or
      treating thromboembolic disorders.

PMID- 24731556
TI  - The association between red cell distribution width and venous thromboembolism: a
      biochemical evaluation.

PMID- 24731557
TI  - Platelet count, platelet turnover and fibrin clot structure in patients with
      coronary artery disease.

PMID- 24731558
TI  - Platelet activation patterns are different in mouse models of diabetes and
      chronic inhibition of nitric oxide synthesis.
AB  - Currently, there are several animal models of diabetes mellitus and hypertension,
      but relatively little is known about blood platelet function in these models. The
      aim of this work was to characterise and compare platelet reactivity and
      activation in db/db mice (mouse model of diabetes) and mice receiving L-NAME
      (model of chronic inhibition of NO synthesis), using various platelet function
      assays. We found higher platelet activation (circulating resting platelets) in
      db/db mice than in db/+heterozygotes, as evidenced by elevated expressions of
      CD62P and CD40L and a lower expression of CD42b. The expression of COX-1 was
      significantly increased, and the phosphorylation of vasodilator stimulated
      phosphoprotein (VASP) Ser(157) significantly reduced in platelets from db/db
      mice. Similarly, we observed platelet hyperreactivity in db/db mice following the
      in vitro responses to 20MUg/ml collagen (reflected by increased expressions of
      CD62P and CD40L, and reduced CD42b), 20MUM ADP (reduced CD42b) and lower
      concentrations of thrombin (0.025 U/ml) (increased CD62P, JON/A, bound vWF, and
      bound fibrinogen). Otherwise, platelet hyporeactivity was revealed for higher
      thrombin (0.25 U/ml) (reduced CD62P and bound vWF), while hyperreactivity
      occurred for CD40L and bound Fg in db/db mice compared to non-diabetic control,
      db/+. Plasma levels of sCD40L, but not of sCD62P, were increased in db/db mice;
      also plasma TXB2 concentrations were over 3.5-fold higher in this group than in
      the heterozygous db/+mice (P<0.01). In contrast, in the mice administered with L
      NAME, no statistical differences in expressions of platelet activation markers
      were found between mice supplemented with L-NAME and controls. Likewise, the TXB2
      level did not differ between L-NAME mice and controls, but L-NAME mice had
      significantly higher plasma levels of sCD62P and sCD40L than controls. In
      conclusion, these two studied models differ in the overall picture of blood
      platelet activation and reactivity, as they demonstrated opposite time sequence
      patterns of platelet activation in circulating blood. More generally, our study
      provides another argument for the opinion that multiparametric analysis of
      platelet function offers a much better tool for investigation and minimizes the
      likelihood of artefacts. 

PMID- 24731559
TI  - Clonal populations of hematopoietic cells with paroxysmal nocturnal
      hemoglobinuria phenotype in patients with splanchnic vein thrombosis.
AB  - INTRODUCTION: Splanchnic vein thrombosis (SVT) is a serious complication in
      patients with paroxysmal nocturnal hemoglobinuria (PNH). Mutant PNH clones can be
      associated with an increased risk of SVT even in the absence of overt disease,
      but their prevalence in non-selected SVT patients remains unknown. MATERIALS AND
      METHODS: Patients with objective diagnosis of SVT and without known PNH were
      tested for the presence of PNH clone using high-sensitivity flow cytometric
      analysis. RESULTS: A total of 202 SVT patients were eligible, 58.4% were males,
      mean age was 54.6years (range 17-94), site of thrombosis was portal in 103
      patients, mesenteric in 67, splenic in 37, and supra-hepatic in 10. SVT was
      associated with JAK2 V6167F in 28 of 126 (22.2%) screened patients, liver
      cirrhosis in 15.3% patients, recent surgery in 10.9%, and myeloproliferative
      neoplasm in 10.6%, whereas in 34.6% of patients neither permanent nor transient
      risk factors were detected. None of the patients had a clearly demonstrable PNH
      clone, but in two patients (0.99%, 95% CI 0.17-3.91) we observed very small PNH
      clones (size 0.014% and 0.16%) confirmed in two independent samples. One patient
      had portal vein thrombosis and no associated risk factors, the second had
      superior mesenteric vein thrombosis and inflammatory bowel disease. CONCLUSIONS:
      Very small PNH clones can be detected in patients with SVT and no clinical
      manifestations of disease. Future studies are needed to explore the potential
      role of this finding in the pathogenesis of SVT.

PMID- 24731560
TI  - Pharmacodynamics assessment of Bemiparin after multiple prophylactic and single
      therapeutic doses in adult and elderly healthy volunteers and in subjects with
      varying degrees of renal impairment.
AB  - INTRODUCTION: Aging and renal impairment may prolong the half-life and lead to
      accumulation of low molecular weight heparins. Correct dosing is critical to
      prevent bleeding or thrombosis. MATERIALS AND METHODS: Open, parallel study.
      Healthy adult [n=13] and elderly (>65yrs) [n=12] volunteers; and subjects with
      mild (ClCr>=50 to <=80mL/min, n=8), moderate (ClCr>=30 to <50mL/min, n=7), and
      severe (ClCr<30mL/min, n=8) renal impairment received four prophylactic doses
      (3,500IU/24h) and a single therapeutic dose (115IU/kg) of bemiparin with an
      interim washout period. Anti-FXa activity and the potential need for dose
      adjustment were evaluated. RESULTS: There were statistically significant
      differences in the severe renal impairment group vs. adult volunteers in all anti
      FXa related parameters, but no significant differences in any of the anti-FXa
      related parameters between the adult and the elderly. Anti-FXa simulations after
      10 prophylactic doses predicted mean Amax=0.59IU/mL in subjects with severe renal
      impairment and 0.33-0.39IU/mL in the rest. Simulations in the severe renal
      impairment group with dose adjustment (2,500IU/24h) predicted all individual
      Amax<0.60IU/mL (mean Amax=0.42IU/ml). Simulations after 10 therapeutic doses
      predicted mean Amax=1.22IU/mL in severe renal impairment group and 0.89-0.98IU/mL
      in the rest. Simulations in the severe renal impairment group with 75% dose
      adjustment predicted individual Amax<=1.60IU/mL (mean Amax=0.91IU/mL).
      CONCLUSIONS: No dose adjustments are required in elderly with preserved renal
      function. A dose adjustment of bemiparin is only advisable in patients with
      severe renal impairment when using prophylactic or therapeutic doses.

PMID- 24731561
TI  - Symptomatic thromboembolic events in patients treated with intravenous
      immunoglobulins: results from a retrospective cohort study.
AB  - AIMS: To estimate the incidence and predictors of symptomatic arterial and venous
      thromboembolic events (TEE) from intravenous immunoglobulin (IVIg) therapy
      according to its indications. METHODS: We performed a retrospective cohort study
      of patients seen at our institution and treated with IVIg over a 36-month period.
      Indications, comorbility and comedication associated with TEE were identified by
      a stepwise logistic regression analysis. RESULTS: Of 303 patients included with
      at least one infusion of IVIg over three years, TEE were identified in a total of
      50 patients treated with IVIg, for an incidence of 16.9% (CI 95%: 13.0-21.6); 27
      (54%) arterial (9.1%;CI 95%: 6.3-13.0%) and 23 (46%) venous TEE (7.8%; CI95%: 5.2
      11.4%), overall mortality was 32%. Per indication there were more patients with
      autoimmune conditions, secondary immunodeficiency, dysimmune neuropathies, acute
      rejection of solid organ transplantation and sepsis. Patients with TEE were
      significantly older, were more likely to be men, they had more comorbid
      conditions; the doses of IVIg were high (589.4mg/kg/day vs 387.0mg/kg/day,
      p<0.001) and differences in comedication were found. The stepwise logistic
      regression analysis retained high doses of IVIg (OR 3.03; CI 95%: 1.49-5.67) and
      diuretics therapy (OR 1.69; CI 95%: 1.06-3.97) when combined with the usual
      comorbid confounders. CONCLUSIONS: The incidence of TEE from IVIg therapy remains
      high at one in six patients treated. The most remediable factor is a high daily
      IVIg load. Decreasing the daily IVIg dose together with carefully weighing
      diuretics therapy and comorbid risk factors may be the keys to saving lives.

PMID- 24731562
TI  - Response to the authors.

PMID- 24731563
TI  - The kidneys play an important role in the clearance of rFVIIa in rats.
AB  - INTRODUCTION: Previous distribution and histological studies have indicated that
      the kidneys and renal proximal tubular cells play a role in clearance of rFVIIa.
      However, the relative importance of the kidneys in clearance of rFVIIa has not
      previously been addressed. The objective of the present study was to evaluate the
      importance of the kidneys in the clearance process of rFVIIa after iv
      administration to rats using a nephrectomy model. MATERIALS AND METHODS: A
      nephrectomized rat model was established and validated using inulin, a compound
      primarily cleared by the kidneys, as a test substance and several physiological
      parameters were monitored to ensure viability and robustness of the model. The
      model was then used for pharmacokinetic evaluation of renal clearance of rFVIIa.
      The pharmacokinetic parameters for rFVIIa were evaluated both by use of standard
      non-compartmental methods and by use of mixed effects methods, where a
      pharmacokinetic model was used to simultaneously model all data from healthy,
      sham operated, and nephrectomized rats. RESULTS: Nephrectomized animals showed
      stable rectal temperature, SpO2 and pulse and as expected, clearance of inulin
      was essentially abolished compared to control animals (p<0.001). For rFVIIa,
      nephrectomy resulted in a clearance and terminal half-life of 34mL/h/kg and 2.8h
      compared to 68mL/h/kg and1.9h in rats exposed to sham surgery (p<0.0001 for both
      parameters). CONCLUSION: The present data show that about 50% of the total
      clearance of rFVIIa from circulation in rats under isoflurane anaesthesia is due
      to renal clearance.

PMID- 24731564
TI  - Baffle thrombosis in an adult with remote prior scimitar vein repair mimicking
      massive pulmonary embolism.
AB  - A 58-year-old man with a history of Scimitar syndrome diagnosed and surgically
      repaired in early adulthood presented multiple times to the emergency department
      complaining dyspnea, chest pain, and hemoptysis. Asymmetric pulmonary arterial
      flow rates between left and right lungs resulted in an apparent filling defect on
      computed tomographic pulmonary arteriography, which was repeatedly misdiagnosed
      clinically and radiologically as a massive pulmonary embolus. This case
      highlights the importance of understanding the pathophysiology and post-surgical
      complications of repaired congenital cardiovascular disease. Delayed phase
      acquisitions are often necessary to characterize the physiology of repaired
      congenital cardiovascular disease with associated shunts. 

PMID- 24731565
TI  - Time to unravel the conceptual confusion of authenticity and fidelity and their
      contribution to learning within simulation-based nurse education. A discussion
      paper.
AB  - High-fidelity patient simulation is a method of education increasingly utilised
      by educators of nursing to provide authentic learning experiences. Fidelity and
      authenticity, however, are not conceptually equivalent. Whilst fidelity is
      important when striving to replicate a life experience such as clinical practice,
      authenticity can be produced with low fidelity. A challenge for educators of
      undergraduate nursing is to ensure authentic representation of the clinical
      situation which is a core component for potential success. What is less clear is
      the relationship between fidelity and authenticity in the context of simulation
      based learning. Authenticity does not automatically follow fidelity and as a
      result, educators of nursing cannot assume that embracing the latest technology
      based educational tools will in isolation provide a learning environment
      perceived authentic by the learner. As nursing education programmes increasingly
      adopt simulators that offer the possibility of representing authentic real world
      situations, there is an urgency to better articulate and understand the terms
      fidelity and authenticity. Without such understanding there is a real danger that
      simulation as a teaching and learning resource in nurse education will never
      reach its potential and be misunderstood, creating a potential barrier to
      learning. This paper examines current literature to promote discussion within
      nurse education, concluding that authenticity in the context of simulation-based
      learning is complex, relying on far more than engineered fidelity. 

PMID- 24731566
TI  - Role of platelet derived growth factor (PDGF) in reverting neuronal nuclear and
      soma size alterations in NSC-34 cells exposed to cerebrospinal fluid from
      amyotrophic lateral sclerosis patients.
AB  - PURPOSE: Amyotrophic lateral sclerosis (ALS) or motor neuron disease is an adult
      onset progressive neurodegenerative disorder. ALS-CSF has been shown to produce
      toxic effects on motor neuron cells like aberrant neurofilament phosphorylation
      and morphological alterations of nuclear and soma size. Our current study was
      designed to investigate the neuroprotective role of platelet derived growth
      factor (PDGF) in reverting the adverse effects produced by ALS-CSF. METHODS: Our
      present study was carried out to determine the restorative potential of PDGF on
      the toxic effects of ALS-CSF on NSC motor neuron cells from patients. Therefore
      the cells were divided in to three groups: (a) normal control (NC) - the cells
      were not exposed to ALS-CSF; (b) ALS group - the cells were exposed to ALS-CSF;
      (c) NALS group - the cells were exposed to non ALS CSF. Further each of these
      groups was supplemented with PDGF. RESULTS AND CONCLUSIONS: We observed that the
      mean area of nucleus and cell soma of the differentiated NSC motor neuron cells
      was significantly reduced in the cells exposed to ALS-CSF. We also observed that
      subsequent treatment with PDGF restored the soma area and nucleus of the ALS-CSF
      exposed cells significantly. Taken together, we show that supplementation with
      PDGF restores the morphological changes induced by ALS-CSF and PDGF may play a
      significant role in protecting motor neurons from apoptosis in ALS and thereby it
      promoting the cell survival.

PMID- 24731567
TI  - Efficacy and safety of intensive statin therapy in Chinese patients with
      atherosclerotic intracranial arterial stenosis: a single-center, randomized,
      single-blind, parallel-group study with one-year follow-up.
AB  - OBJECTIVES: The purpose of this study is to validate the efficacy of intensive
      statin therapy for patients with atherosclerotic intracranial arterial stenosis
      (AICAS). METHODS: In this study, we performed a single-center, randomized, single
      blind, parallel-group clinical trial. A total of 120 Chinese patients with AICAS
      were enrolled and randomly divided into three groups [low-dose atorvastatin
      therapy (LAT, 10mg/day), standard-dose atorvastatin therapy (SAT, 20mg/day), and
      intensive-dose atorvastatin therapy (IAT, 40mg/day) groups] in a 1:1:1 ratio.
      Evaluation variables, including changes in serum lipid profiles, degree of
      stenosis, and perfusion-related parameters derived from computed tomography
      perfusion (CTP) imaging from baseline to weeks 26 and 52, as well as the
      occurrence of cerebrovascular events during the study period, were used to
      compare the benefits of these three statin therapies. RESULTS: After 52 weeks of
      treatment, improvement of serum lipid profiles, degree of stenosis, and perfusion
      related parameters were all significantly better in the IAT group. In addition,
      the cumulative probability of cerebrovascular events at 52 weeks was
      significantly lower in the IAT group than in the LAT group, although there was no
      statistical difference between the IAT group and the SAT group. The proportion of
      patients experiencing any adverse event was similar among the three treatment
      groups. Adverse events caused by IAT were generally mild; no serious adverse
      events occurred throughout the entire period of study. CONCLUSION: In conclusion,
      long-term use of IAT appears to be a safe and effective treatment at least for
      Chinese patients with AICAS.

PMID- 24731568
TI  - Hereditary spastic paraparesis in adults. A clinical and genetic perspective from
      Tuscany.
AB  - OBJECTIVE: Hereditary spastic paraparesis or paraplegias (HSPs) are a group of
      neurogenetic conditions with prominent involvement of the pyramidal tracts. Aim
      of this study is the clinical and molecular characterization of a cohort of
      patients with HSP. Moreover, we aim to study the minimum prevalence of HSP in our
      area and to propose a schematic diagnostic approach to HSP patients based on the
      available data from the literature. METHODS: Retrospective/perspective study on
      the subjects with clinical signs and symptoms indicative of pure or complicated
      HSP, in whom other possible diagnosis were excluded by appropriate
      neuroradiological, neurophysiologic and laboratory studies, who have been
      evaluated by the Neurogenetic Service of our Clinic in last two years (2011
      2012). RESULTS: 45 patients were identified. The minimum prevalence of HSP in our
      area was of about 2.17-3.43/100,000. The SF-36 (quality of life) and SPRS
      (disease progression) scores were inversely related; the time-saving, four-stage
      scale of motor disability could predict the SPRS scores with a high statistical
      significance, and we encourage its use in HSP. Our study confirms SPG4 as the
      major cause of HSP. All SPG4 patients had a pure HSP phenotype, and the dominant
      inheritance was evident in the great majority of these subjects. SPG7 was the
      second genetic cause. Other genotypes were rarer (SPG10, SPG11, SPG17).
      CONCLUSION: Exact molecular diagnosis will allow a more accurate patient
      counseling and, hopefully, will lead to specific, targeted, therapeutic options
      for these chronic, still incurable diseases.

PMID- 24731569
TI  - Post-traumatic occipito-cervical pseudomeningocele without any bony injury.

PMID- 24731570
TI  - Comparison of CT and MRI findings for cervical spine clearance in obtunded
      patients without high impact trauma.
AB  - OBJECTIVE: Cervical spinal injuries occur in 2.0-6.6% of patients after blunt
      trauma and can have devastating neurological sequelae if left unrecognized.
      Although there is high quality evidence addressing cervical clearance in
      asymptomatic and symptomatic awake patients, cervical spine clearance in patients
      with altered level of alertness (i.e., obtunded patients with Glasgow coma scale
      (GCS) of 14 or less) following blunt trauma has been a matter of great
      controversy. Furthermore, there are no data on cervical spine clearance in
      obtunded patients without high impact trauma and these patients are often treated
      based on evidence from similar patients with high impact trauma. This
      retrospective study was conducted on this specific subgroup of patients who were
      admitted to a neurointensive care unit (NICU) with primary diagnoses of
      intracranial hemorrhage with history of minor trauma; the objective being to
      evaluate and compare cervical spinal computed tomography (CT) and magnetic
      resonance imaging (MRI) findings in this particular group of patients. METHODS:
      Patients with GCS of 14 or less admitted to neruointensive care unit (NICU) at
      RUSH University Medical Center from 2008 to 2010 with diagnoses of intracranial
      hemorrhage (surgical or non-surgical) who had reported or presumed fall (i.e.,
      "found down") were queried from the computer data registry. A group of these
      patients had cervical spine CT and subsequently MRI for clearing the cervical
      spine and removal of the cervical collar. Medical records of these patients were
      reviewed for demographics, GCS score and injury specific data and presence or
      absence of cervical spine injury. RESULTS: Eighty-three patients were identified
      from the computer database. Twenty-eight of these patients had positive findings
      on both CT and MRI (33.73% - Group I); four patients had a negative CT but had
      positive findings on follow-up MRI (4.82% - Group II); fifty-one patients had
      both negative CT and MRI (61.44% - Group III). All patients in Group I required
      either surgical stabilization or continuation of rigid cervical orthosis. All
      four patients in Group II had intramedullary T2 hyper intensity consistent with
      possible spinal cord injury on MRI, but did not have any signs of fracture or
      ligamentous injury to suggest instability. They eventually underwent surgical
      decompression of the spinal cord during the same hospital stay. Cervical collars
      were safely removed in all patients in Group III. In our retrospective study, CT
      had a sensitivity of 0.875 [0.719-0.950, 95% CI] and a specificity of 1.000
      [0.930-1.000, 95% CI] in detecting all cervical spine injuries compared to MRI.
      However, all patients with missed injuries had intramedullary T2 hyper intensity
      consistent with possible spinal cord injury on MRI and were not unstable
      precluding cervical spine clearance. If only unstable injuries are considered, CT
      had a sensitivity of 1.00 [0.879-1.000, 95% CI] and a specificity is 1.000 [0.935
      1.000, 95% CI] compared to MRI in this particular group of patients. CONCLUSION:
      CT is highly sensitive in detecting unstable injuries in obtunded patients with
      GCS of 14 or less in the absence of high impact trauma. In the absence of high
      impact trauma, neurosurgeons should be comfortable to discontinue the cervical
      collar after a negative, high-quality CT in this patient population. In the
      presence of focal neurological deficits unexplained by associated intracranial
      injury, an MRI may help diagnose intrinsic spinal cord injuries which necessarily
      may not be unstable in the presence of a negative CT and does not precludes
      clearance of cervical spine.

PMID- 24731571
TI  - Hydrocephalus after resection and adjuvant radiochemotherapy in patients with
      glioblastoma.
AB  - OBJECTIVE: Glioblastomas are the most common primary malignant brain tumors in
      adults with a poor prognosis. The current study sought to identify risk factors
      in glioblastoma patients that are closely associated with communicating
      hydrocephalus. METHODS: We retrospectively analyzed data from 151 patients who
      were diagnosed with a glioblastoma between 2007 and 2011 and underwent complete
      surgical resection closely followed by adjuvant radiochemotherapy. RESULTS: We
      observed a significant tendency toward communicating hydrocephalus in cases of
      ventricular opening during surgical tumor resection (Fisher's exact test p<0.001)
      and a noticeable, although not statistically significant, correlation between the
      onset of communicating hydrocephalus and evidence of leptomeningeal tumor
      dissemination (Fisher's exact test p=0.067). Additionally, there was a trend
      toward frontal tumor location and a larger tumor volume in patients with
      communicating hydrocephalus. The majority of patients suffering from
      communicating hydrocephalus received a cerebrospinal fluid (CSF) shunt
      implantation after radiation therapy (63.6%, Fisher's exact test p=0.000).
      CONCLUSION: We identified the following risk factors associated with the onset of
      communicating hydrocephalus in glioblastoma patients: ventricular opening during
      tumor resection and leptomeningeal tumor dissemination. Shunt implantation seems
      to be safe and effective in these patients.

PMID- 24731572
TI  - Sodium fluorescein in skull base meningiomas: a technical note.
AB  - OBJECTIVES: Skull base meningiomas are a neurosurgical challenge due to the
      involvement of neurovascular structures. In this study, the authors present the
      first study of the trans-operative use of sodium fluorescein (SF) to enhance
      skull base meningiomas and perform a quantitative digital analysis of the tumors'
      pigmentation. The goal of the study was to observe the SF enhancement of skull
      base meningiomas. PATIENTS AND METHODS: A prospective, within-subjects study was
      designed and performed. This study included twelve patients with skull base
      meningiomas. After an initial dissection, digital pictures were taken before and
      after systematic injections of SF using the same light-source used for the
      surgical microscope. These pictures were analyzed with software that calculated
      the wavelengths of the sodium fluorescein before and after the injection of the
      dye. RESULTS: The meningiomas in the sample included the following types: 1
      cavernous sinus, 1 olfactory groove, 3 petroclival, 1 tuberculum sellae, 3
      sphenoid wings, 1 anterior clinoid, and 2 temporal floor. The SF enhancement in
      all tumors was strongly positive. CONCLUSIONS: The low cost, universal
      availability and safety of SF indicate that this dye should be examined in
      further studies, and its applications in skull-base meningioma surgeries should
      be further assessed.

PMID- 24731573
TI  - Clinical experience with telemetric intracranial pressure monitoring in a Danish
      neurosurgical center.
AB  - BACKGROUND: Monitoring of intracranial pressure (ICP) is important in the optimal
      treatment of various neurological and neurosurgical diseases. Telemetric ICP
      monitoring allows long-term measurements in the patient's everyday life and the
      possibility to perform additional measurements without the procedure related
      risks of repeated transducer insertions. MATERIALS AND METHODS: We identified all
      patients in our clinic with an implanted Raumedic((r)) telemetric ICP probe
      (NEUROVENT((r))-P-tel). For each patient we identified diagnosis, indication for
      implantation, surgical complications, duration of ICP reading, number of ICP
      recording sessions (in relation to symptoms of increased ICP) and their clinical
      consequence. RESULTS: We included 21 patients in the evaluation (11 female and 10
      male). Median age was 28 (2-83) years and median duration of disease was 11 (0
      30) years. Eleven patients had various kinds of hydrocephalus, seven patients had
      idiopathic intracranial hypertension (IIH) and three patients had normal pressure
      hydrocephalus (NPH). Fifteen patients had a shunt prior to implantation. Median
      duration of implantation was 248 (49-666) days and median duration from
      implantation to last recording session was 154 (8-433) days. In total, 86
      recording sessions were performed; 29 resulted in surgical shunt revision, 30 in
      change of acetazolamide dose or programmable valve setting, 20 required no action
      and 5 resulted in a new recording session. No surgical complications occurred,
      except for late wound infection at the surgical site in two patients. CONCLUSION:
      Telemetric ICP monitoring is useful in patients with complicated CSF dynamic
      disturbances who would otherwise require repeated invasive pressure monitoring.
      It seems to be a feasible method to guide adjustment of programmable valve
      settings and to identify patients with chronic or repeated shunt problems.

PMID- 24731574
TI  - Lower complication rates for cranioplasty with peri-operative bundle.
AB  - BACKGROUND: The overall benefits of craniectomy must include procedural risks
      from cranioplasty. Cranioplasty carries a high risk of surgical site infections
      (SSI) particularly with antibiotic resistant bacteria. The goal of this study was
      to measure the effect of a cranioplasty bundle on peri-operative complications.
      METHODS: The authors queried a prospective, inpatient neurosurgery database at
      Kaiser Sacramento Medical Center for craniectomy and cranioplasty over a 7 year
      period. 57 patients who underwent cranioplasties were identified. A retrospective
      chart review was completed for complications, including surgical complications
      such as SSI, wound dehiscence, and re-do cranioplasty. We measured cranioplasty
      complication rates before and after implementation of a peri-operative bundle,
      which consisted of peri-operative vancomycin (4 doses), a barrier dressing
      through post-operative day (POD) 3, and de-colonization of the surgical incision
      using topical chlorhexidine from POD 4 to 7. RESULTS: The rate of MRSA
      colonization in cranioplasty patients is three times higher than the average seen
      on ICU admission screening (19% vs. 6%). The cranioplasty surgical complication
      rate was 22.8% and SSI rate was 10.5%. The concurrent SSI rate for craniectomy
      was 1.9%. Organisms isolated were methicillin-resistant Staphylococcus aureus
      (4), methicillin-sensitive S. aureus (1), Propionibacterium acnes (1), and
      Escherichia coli (1). Factors associated with SSI were peri-operative vancomycin
      (68.6% vs. 16.7%, p=0.0217). Complication rates without (n=21) and with (n=36)
      the bundle were: SSI (23.8% vs. 2.8%, p=0.0217) and redo cranioplasty (19% vs.
      0%, p=0.0152). Bundle use did not affect rates for superficial wound dehiscence,
      seizures, or hydrocephalus. CONCLUSIONS: The cranioplasty bundle was associated
      with reduced SSI rates and the need for re-do cranioplasties.

PMID- 24731575
TI  - Association between promoter region of the uPAR (rs344781) gene polymorphism in
      genetic susceptibility to migraine without aura in three Iranian hospitals.
AB  - INTRODUCTION: Migraine is a chronic neurological disorder. Inflammation has a key
      role in migraine pathophysiology. Urokinase plasminogen activator receptor (uPAR)
      directly involves in inflammatory conditions by facilitating migration of
      inflammatory cells to different tissues. The aim of this study was to investigate
      whether uPAR rs344781, common genetic polymorphism in the uPAR promoter region,
      might be associated with migraine without aura susceptibility in an Iranian
      population. METHODS: We enrolled 103 newly diagnosed patients with migraine and
      100 healthy controls. Peripheral blood sample was used for DNA extraction and
      uPAR rs344781 gene polymorphism was determined. Patients filled HIT-6 as a tool
      to evaluate headache severity. RESULTS: The genotype frequency of uPAR is
      significantly different between migraine patients and control subjects.
      Heterozygote genotype (AG) was statistically more frequent in the patients than
      the controls (P=0.001; OR=2.67, 95% CI=1.51-4.7). Also G allele was more frequent
      in the patients. Total HIT-6 score was not significantly different between
      heterozygote and homozygote patients (55.50+/-2.22 vs. 49.60+/-3.68 respectively,
      P=0.075). CONCLUSION: In conclusion, our study showed a significant association
      between uPAR rs344781 gene promoter polymorphism and migraine without aura
      susceptibility but not with headache severity.

PMID- 24731576
TI  - Influence of antiplatelet therapy on postoperative recurrence of chronic subdural
      hematoma: a multicenter retrospective study in 719 patients.
AB  - OBJECTIVE: The present study tested the hypothesis of whether antiplatelet agents
      (APA) induce chronic subdural hematoma (CSDH) recurrence via a platelet
      aggregation inhibitory effect. METHOD: We examined risk factors for CSDH
      recurrence, focusing on APA, in 719 consecutive patients who admitted to three
      tertiary hospitals and underwent burr-hole craniostomy and irrigation for CSDH.
      This was a multicenter, retrospective, observational study. RESULTS: Age, sex,
      history of diabetes mellitus, hypertension, chronic renal failure, alcohol
      consumption habits, consciousness disturbance on admission, or preoperative CT
      density was not associated with recurrence. Subdural drainage was significantly
      associated with less recurrence. Preoperative oral APA administration was
      significantly associated with more recurrence. The recurrence rate of CSDH in non
      APA group was 11% if surgery was performed on admission. However, if surgery was
      performed immediately after discontinuation of oral APA administration, the
      recurrence rate in APA group significantly increased to 32% (p value<0.0001; odds
      ratio, 3.77; 95% confidence interval, 1.72-8.28). The effect of APA on CSDH
      recurrence gradually diminished as the number of days until initial surgery,
      after stopping APA, increased. CONCLUSION: Antiplatelet therapy significantly
      influences the recurrence of CSDH.

PMID- 24731577
TI  - Practice patterns of in-hospital surgical treatment of trigeminal neuralgia from
      1988 to 2010.
AB  - OBJECTIVE: Neurosurgeons have a variety of procedures to offer when treating
      medically intractable trigeminal neuralgia (TN). We reviewed the national trends
      in procedural volume for in-hospital treatment of TN. METHODS: The Nationwide
      Inpatient Sample (1988-2010) provided data on patients hospitalized with a
      principal diagnosis of TN and a related principal procedure. We categorized
      principal procedures as open, other, percutaneous, or radiosurgery. RESULTS: We
      identified 13,466 relevant hospital admissions. The volume for open procedures
      and radiosurgery remained relatively constant, whereas percutaneous procedures
      decreased. Mean age of patients undergoing percutaneous and radiosurgery
      procedures (67.9 and 69.5 years) was higher than open and other procedures (60.4
      and 63.4 years) (p-value <0.001). The mean total in-hospital inflation-adjusted
      charges for all four categories increased over time (p-values <0.001). The mean
      total in-hospital inflation-adjusted charge for radiosurgery ($37,666) was higher
      than open ($28,046) procedures (p-value <0.001). CONCLUSIONS: Patients who
      undergo an open procedure to treat TN are younger than those who undergo a
      percutaneous or a radiosurgery procedure. The perceived risk of open surgery in
      older patients may drive offering percutaneous or radiosurgical procedures. In
      addition, the in-hospital inflation-adjusted charges for all procedures increased
      over time, with radiosurgery being higher than those of open procedures.

PMID- 24731578
TI  - Prediction parameters of bone flap resorption following cranioplasty with
      autologous bone.
AB  - OBJECTIVE: The number of patients who need cranioplasty after decompressive
      craniectomy has increased. In most cases, autologous bone flaps are used for
      cranioplasty, and there have been reports of the complication of bone flap
      resorption. Based on these facts, we analysed patients who underwent cranioplasty
      in our institution to learn about potential risk factors of cranioplasty. METHODS
      AND RESULTS: We performed a retrospective study and analysed 58 patients who
      underwent cranioplasty between 2006 and 2013. We found that patients with a
      defect size >120cm(2) whose reimplantation was delayed tended to have a risk of
      bone flap resorption. CONCLUSION: Patients with delayed reimplantation and a
      defect size >120cm(2) show a tendency of aseptic bone flap resorption. In these
      cases, a patient-specific implant (PSI) could be the first choice material for
      this procedure to reduce the rate of this complication.

PMID- 24731580
TI  - Carotid siphon calcification impact on revascularization and outcome in stroke
      intervention.
AB  - OBJECTIVE: The degree of coronary artery calcification has been shown to predict
      outcomes in coronary artery disease. The impact of intracranial carotid artery
      calcification on the prognosis of acute ischemic stroke (AIS) is unknown. The
      authors sought to examine if the degree of intracranial carotid artery
      calcification influences reperfusion or outcomes in AIS intervention. METHODS:
      All anterior circulation large vessel occlusion AIS cases that underwent intra
      arterial therapy from January 2009 to July 2012 were reviewed. Clinical and
      radiographic data were collected. Non-contrast brain CT scans were assigned a
      Calcium Extent Score (degree of calcification of the carotid wall circumference),
      Calcium Thickness Score (thickness of the calcified plaque), and total Carotid
      Siphon Calcium (CSC) Score (8-point scale). RESULTS: One-hundred seventeen
      patients met inclusion criteria. The mean age was 65.4+/-15.6 years and 36% were
      male. Calcification was present in the intracranial carotid artery of 84 patients
      (71%). Inter-rater agreement for total CSC score was strong (Spearman's
      rho=0.883, p<0.001). The mean Calcium Extent Score was 1.5+/-1.3, Calcium
      Thickness Score 1.3+/-1.0 and total CSC Score 2.8+/-2.2. Reperfusion and mRS were
      not associated with CSC. Multivariate linear regression analysis revealed that
      older age, history of coronary disease and cervical internal carotid
      occlusion/near-occlusion were independently associated with higher total CSC
      scores. CONCLUSION: Extensive calcification on the intracranial carotid artery
      does not have impact on reperfusion or clinical outcomes in AIS patients
      undergoing endovascular therapy. Higher CSC scores are associated with coronary
      artery disease, increasing age and cervical internal carotid artery
      occlusion/near-occlusion.

PMID- 24731579
TI  - Cervical spondylotic myelopathy in the young adult: a review of the literature
      and clinical diagnostic criteria in an uncommon demographic.
AB  - BACKGROUND: Cervical spondylotic myelopathy (CSM) is typically encountered in the
      elderly population. Significant inconsistencies currently exist regarding the
      definition of the disorder, the true incidence of CSM in younger populations, and
      the established diagnostic criteria. OBJECTIVE: To highlight the lack of
      standardization in the definition and diagnosis of CSM. METHODS: A PubMed
      literature search was conducted spanning the years 2001-2011. The search was
      limited by the following terms: (1) English language, (2) adults (19-44 years
      old), and (3) "cervical spondylotic myelopathy." Each article was reviewed to
      determine if the presence of the definition of CSM existed in the article. The
      clinical characteristics used to make the diagnosis of CSM were recorded for each
      article. Cochran's Q statistic was used to determine whether some clinical
      characteristics were more frequently used than others. RESULTS: Ninety-three
      papers were reviewed in detail and 16 case reports, reviews, and articles
      concerning less than 3 patients were excluded, resulting in 77 articles in the
      final analysis. The most common clinical definitions were gait disturbance (22/77
      articles (28.6%)), upper limb paresthesias or sensory disturbance (21/77
      (27.3%)), and clumsy hands (15/77 (19.5%)). Hyperreflexia, spasticity, and
      pathologically increased reflexes were identified as diagnostic criteria in a
      minority of patients. CONCLUSION: The literature employs a wide range of
      neurologic signs and symptoms to make the diagnosis of CSM, with a majority of
      studies failing to rely on strict diagnostic criteria. The clinician should not
      discount CSM as an explanation for the aforementioned findings, as it is well
      reported in the literature among the ages 18-44.

PMID- 24731581
TI  - Risk factor profile by etiological subtype of ischemic stroke in the young.
AB  - BACKGROUND AND PURPOSE: Studies of risk factors for ischemic stroke in the young
      have generally considered ischemic stroke as a whole. The purpose of the present
      study was to evaluate the association of traditional cardiovascular risk factors
      with etiological subtypes of ischemic stroke in young adults. METHODS:
      Retrospective review of data from patients aged 16-54 years consecutively treated
      for first-ever ischemic stroke in an academic stroke unit. Definite causes of
      stroke were classified using the ASCO (A for atherothrombosis, S for small vessel
      disease, C for cardiac source, O for other cause) classification system. We used
      multinomial logistic regression analysis to evaluate associations of age, gender,
      smoking, hypertension, diabetes and blood lipids with each etiological subtype.
      RESULTS: A total of 400 patients were included: 244 men (61.1%), 156 women
      (38.9%); mean age (SD) 44.5 (8.5) years. A definite cause of stroke could be
      identified in 202 (50.5%) patients. Definite causes of stroke included:
      atherothrombosis, 72 (18.0%) patients; cardioembolism, 37 (9.25%) patients; small
      vessel disease, 28 (7.0%) patients; other definite cause, 65 (16.25%) patients
      including 44 patients with carotid or vertebral artery dissection.
      Atherothrombosis was associated with age, smoking, diabetes, hypertension and low
      HDL-cholesterol. Small vessel disease was associated with age and hypertension.
      Cardioembolism was associated with age. CONCLUSION: The risk factor profile
      differs between etiological subtypes of ischemic stroke in young adults. Our
      findings emphasize the impact of smoking, diabetes, hypertension and low HDL
      cholesterol as risk factors for atherothrombosis, and of hypertension as a risk
      factor for small vessel disease in young adults.

PMID- 24731582
TI  - Patency of the posterior communicating artery after flow diversion treatment of
      internal carotid artery aneurysms.
AB  - BACKGROUND AND PURPOSE: Cerebral aneurysm treatment with the Pipeline
      Embolization Device (PED) often mandates device placement across the ostia of
      arteries of the Circle of Willis. We determined the patency rates of the
      posterior communicating artery (Pcomm) after placement across its ostium a PED
      and studied neurologic outcomes in these patients. METHODS: We analyzed,
      retrospectively, a consecutive series of patients in whom a PED was placed across
      the ostium of Pcomm while treating the target aneurysm. Pcomm arterial flow after
      PED placement was graded on a 3-point scale at post-operative angiography and
      follow-up angiography. Data on pretreatment aneurysm rupture status, concomitant
      coiling, number of PEDs used, and neurologic status at follow-up were collected.
      RESULTS: Eleven patients with 13 aneurysms were included in this study. All
      patients had an ipsilateral posterior cerebral artery arising from the basilar
      artery (P1). In the immediate post-procedural setting, four patients (36%) had
      diminished Pcomm flow rates. After a mean follow-up of 12.6+/-6.7 months, three
      Pcomm arteries (27%) were occluded and two Pcomm arteries (18%) had diminished
      flow. Of patients with diminished flow/occluded Pcomm at follow-up, 80% (4/5) had
      diminished flow at initial post-procedure angiography compared to none of the six
      patients without diminished/occluded flow immediately post treatment. No patients
      suffered new neurologic symptoms at follow-up. CONCLUSIONS: Approximately one
      half of Pcomm arteries demonstrated occlusion or decreased flow at follow-up if
      the ostia are covered with a flow diversion device. Covering the Pcomm ostium in
      patients with a P1 did not result in any neurologic deficits.

PMID- 24731583
TI  - Selective serotonin reuptake inhibitors prolong seizures - preliminary results
      from an observational study.
AB  - OBJECTIVE: Selective serotonin reuptake inhibitors (SSRIs) are often used in the
      treatment of depressive disorders in patients with epilepsy. Pro- and anti
      convulsive effects of SSRIs are discussed controversially. The aim of this study
      was to investigate a possible impact of SSRIs-treatment on duration of EEG and
      clinical features in epilepsy patients. METHODS: We studied video-EEG data from
      162 patients with focal epilepsies between January 2006 and March 2008 using a
      case-control study design. Eleven patients with 19 complex focal seizures (CFSs)
      and 16 secondary generalized tonic-clonic seizures (sGTCSs) treated with SSRIs
      (SSRIs+) were matched to 13 patients without SSRIs-treatment (SSRIs-). We
      compared duration of ictal EEG in CFSs and sGTCSs, duration of convulsions in
      sGTCSs and duration of postictal EEG suppression after sGTCSs in SSRIs+ and SSRIs
      patients. RESULTS: Ictal EEG duration of both, CFSs and sGTCSs, was
      significantly longer in SSRIs+ patients than in SSRIs- patients (p=0.004 and
      p=0.015, respectively). No significant difference was found between convulsive
      phase duration of sGTCSs as well as duration of postictal EEG suppression after
      sGTCSs in both groups. CONCLUSION: Seizures last significantly longer in patients
      with epilepsy and SSRIs as co-medication. A causative role of SSRIs in ictal
      activity has to be explored in prospective studies.

PMID- 24731584
TI  - Bilateral sciatic neuropathy due to fibrous bands in a patient with severe
      traumatic brain injury.

PMID- 24731585
TI  - Comparison of morphologic consequences of open and endoscopic carpal tunnel
      release.
AB  - OBJECTIVES: The objective of this study is to evaluate the carpal canal
      morphologic consequences following endoscopic carpal tunnel release compared with
      open approach. METHODS: 48 Patients with CTS were enrolled in our prospective
      trial. Participants were classified in 2 groups: 24 patients underwent open
      surgery technique and 24 underwent endoscopic carpal tunnel decompression. Carpal
      canal shape and volume, configuration and position of contents, were analyzed by
      using imaging techniques. RESULTS: Preoperative carpal canal volume in endoscopic
      patient group averaged 5.7+/-1.4 cc and 7.3+/-2.9 cc at 6 weeks postoperatively
      (28%+/-7%, p=0.018). In contrast preoperative carpal canal volume in open carpal
      tunnel release group averaged 4.9+/-1.1 cc (and increased to 6.2+/-1.7 cc at 6
      week follow up investigation (36%+/-5%, p=0.002). Preoperative carpal arch width
      calculation in endoscopic carpal tunnel release group averaged 21.7+/-1.1mm and
      21.5+/-1.9mm in open carpal tunnel release patients (p=0.6575). Postoperative
      carpal arch width measurements in endoscopic carpal tunnel decompression group
      averaged 22.6+/-4.1mm and 22.1+/-2.9mm in open carpal tunnel release patient
      population at 6-week follow-up investigation (p=0.628). CONCLUSION: Endoscopic
      approach causes an increment in carpal canal volume comparable to open technique
      and provides equivalent anatomic outcomes and will produce at least equivalent
      long-term clinical relief.

PMID- 24731586
TI  - Multifocal myeloid sarcoma in the central nervous system without leukemia.

PMID- 24731587
TI  - Key determinants of short-term and long-term glioblastoma survival: a 14-year
      retrospective study of patients from the Hermelin Brain Tumor Center at Henry
      Ford Hospital.
AB  - OBJECTIVE: Glioblastoma (GBM) is a heterogeneous neoplasm with a small percentage
      of long-term survivors. Despite aggressive surgical resection and advances in
      radiotherapy and chemotherapy, the median survival for patients with GBM is 12-14
      months. Factors associated with a favorable prognosis include young age, high
      performance status, gross resection >98%, non-eloquent tumor location and O6
      methylguanine methyltransferase (MGMT) promoter methylation. We retrospectively
      analyzed the relationship of clinical, epidemiologic, genetic and molecular
      characteristics with survival in patients with GBM. METHODS: This retrospective
      analysis of overall survival looked at the outcomes of 480 patients diagnosed
      with GBM over 14 years at a single institution. Multivariate analysis was
      performed examining multiple patient characteristics. RESULTS: Median survival
      time improved from 11.8 months in patients diagnosed from 1995 to 1999 to 15.9
      months in those diagnosed from 2005 to 2008. Factors associated with survivor
      groups were age, KPS, tumor resection, treatment received and early progression.
      18 cancer-related genes were upregulated in short-term survivors and five genes
      were downregulated in short-term survivors. CONCLUSIONS: Epidemiologic, clinical,
      and molecular characteristics all contribute to GBM prognosis. Identifying
      factors associated with survival is important for treatment strategies as well as
      research for novel therapeutics and technologies. This study demonstrated
      improved survival for patients over time as well as significant differences among
      survivor groups.

PMID- 24731588
TI  - Concurrent unilateral moyamoya disease and vertebrobasilar junction aneurysm
      associated with fenestration - case report and management.

PMID- 24731589
TI  - Perineural spread of malignant mesothelioma with spinal intramedullary
      involvement.

PMID- 24731590
TI  - Multiple intracranial tumors: coexistence of a glioblastoma and null cell
      pituitary adenoma within the same patient.

PMID- 24731591
TI  - Intravenous thrombolysis in acute ischemic stroke due to occlusion of internal
      carotid artery - a Serbian Experience with Thrombolysis in Ischemic Stroke
      (SETIS).
AB  - OBJECTIVE: The benefit of intravenous thrombolysis in patients with internal
      carotid artery (ICA) occlusion is still unclear. The aim of this study was to
      assess the influence on outcome of intravenous thrombolysis in patients with ICA
      occlusion comparing to those without it. METHODS: Data were from the national
      register of all acute ischemic stroke patients treated with intravenous
      thrombolysis in Serbia. Patients with nonlacunar anterior circulation infarction
      were included and were divided into two groups, those with and those without ICA
      occlusion. We compared the differences in demographic characteristics, risk
      factors, baseline NIHSS score, early neurological improvement, 3-month functional
      outcome, complications and death between these two groups. RESULTS: Among 521
      included patients there were 13.4% with ICA occlusion. Group with ICA occlusion
      had more males (82.9% vs. 60.5%; p=0.0008), and more severe stroke (baseline
      NIHSS score 15.3 vs. 13.6; p=0.004). Excellent functional outcome (mRS 0-1) at 3
      months was recorded in 32.9% patients with ICA occlusion and in 50.6% patients
      without (p=0.009), while favorable functional outcome (mRS 0-2) was recorded in
      50.0% of patients with ICA occlusion vs. 60.1% without (p=0.14). Death occurred
      in 12.9% patients with ICA occlusion and in 17.3% patients without it (p=0.40).
      There was no significant difference in rate of symptomatic ICH between the two
      groups (1.4% vs. 4.2%; p=0.5). Multivariate logistic regression analysis showed
      that ICA occlusion was associated with the absence of early neurological
      improvement (p=0.03; OR 1.78, 95% CI 1.05-3.04). However, the presence of ICA
      occlusion was not significantly associated with an unfavorable outcome at 3-month
      (p=0.44; OR 1.24, 95% CI 0.72-2.16) or with death (p=0.18; OR 0.57, 95% CI 0.25
      1.29). CONCLUSION: The patients with ICA occlusion treated with intravenous
      thrombolysis have a worse outcome than patients without it.

PMID- 24731592
TI  - Quality of language intervention provided to primary-grade students with language
      impairment.
AB  - This study had two aims: (a) to describe the quality of language intervention
      provided by school-based speech-language pathologists (SLPs) to children with
      language impairment in the primary grades with respect to the quality of
      emotional support, instructional support, and proactive management during SLP
      child interactions, and (b) to determine if key characteristics of the SLPs are
      predictors of variance in intervention quality. Participants were 174 children
      nested within 40 SLPs' caseloads from various districts in two Midwestern states
      involved in a larger study of speech-language therapy practices in the public
      schools. A total of 208 videotaped language intervention sessions were coded for
      emotional support, instructional support, and proactive management using the
      Classroom Assessment Scoring System (CLASS; Pianta, La Paro, & Hamre, 2008). The
      quality of language intervention varied widely and was generally mid-range to
      high with respect to emotional support and proactive management, and low to mid
      range in terms of instructional support. The quality of interactions varied and a
      large percentage of the observed variance in quality was attributed to SLPs. Time
      pressure was a strong predictor of the quality of emotional support,
      instructional support, and proactive management, and job satisfaction was a
      significant predictor of instructional support and proactive management. This
      descriptive information about school-based language intervention highlights the
      impact of the individual SLP in terms of the quality of the interactions taking
      place and the potential need to ease job pressures and promote job satisfaction.
      LEARNING OUTCOMES: Readers will be able to: (1) identify and define three aspects
      of SLP-child interaction quality during intervention as framed in this study
      using the CLASS observation tool (Pianta, La Paro, et al., 2008); (2) discuss the
      relevance of those three aspects of quality to children with LI; and (3) identify
      SLP-level factors that significantly predict SLP-student interaction quality
      during intervention for children with LI.

PMID- 24731593
TI  - A molecular dynamic study of cholesterol rich lipid membranes: comparison of
      electroporation protocols.
AB  - We report on a molecular dynamics (MD) simulation study of the electroporation of
      lipid bilayers at different cholesterol contents using protocols mimicking
      "traditional" electroporation, i.e. low intensity millisecond pulses (msEP), and
      high intensity nanosecond electric pulses (nsEP). The results show that addition
      of cholesterol in concentrations of lipid:sterol ranging from 20 to 50 mol%
      enhances substantially the membrane cohesion, which is manifested by an increase
      of the electroporation threshold (U(thr)). This increase is steady in the case of
      the nsEP protocol, reaching roughly a factor 2 in the 50 mol% samples. In
      contrast, for the msEP protocol, U(thr) increases by 50% upon addition of 30 mol%
      cholesterol then levels off. Furthermore, pores formed under msEP are found to
      possess morphologies much different from the usually reported hydrophilic
      "electropores" encountered under the nsEP protocol, which may have profound
      consequences on the transport properties of "electroporated" membranes. Hence,
      this study reveals that cell membrane models containing the ubiquitous
      cholesterol component respond quite differently to the two electroporation
      techniques, in contrast to what has been found for simple zwitterionic bilayers.

PMID- 24731594
TI  - Predicting electroporation of cells in an inhomogeneous electric field based on
      mathematical modeling and experimental CHO-cell permeabilization to propidium
      iodide determination.
AB  - High voltage electric pulses cause electroporation of the cell membrane.
      Consequently, flow of the molecules across the membrane increases. In our study
      we investigated possibility to predict the percentage of the electroporated cells
      in an inhomogeneous electric field on the basis of the experimental results
      obtained when cells were exposed to a homogeneous electric field. We compared and
      evaluated different mathematical models previously suggested by other authors for
      interpolation of the results (symmetric sigmoid, asymmetric sigmoid, hyperbolic
      tangent and Gompertz curve). We investigated the density of the cells and
      observed that it has the most significant effect on the electroporation of the
      cells while all four of the mathematical models yielded similar results. We were
      able to predict electroporation of cells exposed to an inhomogeneous electric
      field based on mathematical modeling and using mathematical formulations of
      electroporation probability obtained experimentally using exposure to the
      homogeneous field of the same density of cells. Models describing cell
      electroporation probability can be useful for development and presentation of
      treatment planning for electrochemotherapy and non-thermal irreversible
      electroporation. 

PMID- 24731595
TI  - Lipolysis in lipid turnover, cancer cachexia, and obesity-induced insulin
      resistance.
AB  - Triglycerides in adipose tissue are rapidly mobilized during times of energy
      needs via lipolysis, a catabolic process that plays important role in whole body
      triglyceride turnover. Lipolysis is regulated through cell surface receptors via
      neurotransmitters, hormones, and paracrine factors that activate various
      intracellular pathways. These pathways converge on the lipid droplet, the site of
      action of lipases and cofactors. Fat cell lipolysis is also involved in the
      pathogenesis of metabolic disorders, and recent human studies have underscored
      its role in disease states such as cancer cachexia and obesity-induced insulin
      resistance. We highlight here topics and findings with physiological and clinical
      relevance, namely lipid turnover in human fat cells and the role of lipolysis in
      cancer cachexia and obesity-induced insulin resistance. 

PMID- 24731596
TI  - Glucose-lowering effects of intestinal bile acid sequestration through
      enhancement of splanchnic glucose utilization.
AB  - Intestinal bile acid (BA) sequestration efficiently lowers plasma glucose
      concentrations in type 2 diabetes (T2D) patients. Because BAs act as signaling
      molecules via receptors, including the G protein-coupled receptor TGR5 and the
      nuclear receptor FXR (farnesoid X receptor), to regulate glucose homeostasis, BA
      sequestration, which interrupts the entero-hepatic circulation of BAs,
      constitutes a plausible action mechanism of BA sequestrants. An increase of
      intestinal L-cell glucagon-like peptide-1 (GLP-1) secretion upon TGR5 activation
      is the most commonly proposed mechanism, but recent studies also argue for a
      direct entero-hepatic action to enhance glucose utilization. We discuss here
      recent findings on the mechanisms of sequestrant-mediated glucose lowering via an
      increase of splanchnic glucose utilization through entero-hepatic FXR signaling. 

PMID- 24731598
TI  - Factors affecting sick leave prescribing in occupational health care: a survey
      based on hypothetical patient cases.
AB  - BACKGROUND: Several studies have shown considerable differences in the way that
      physicians prescribe sick leave. The aim of this study was to examine the sick
      leave prescribing practices of occupational health care physicians and factors
      affecting these practices. METHODS: A questionnaire study with 19 hypothetical
      patient cases was conducted among 356 Finnish occupational health care
      physicians. The effects of both physician-related and local structural background
      variables on sick leave prescribing were studied using regression models.
      Economic consequences of the variation in sick leave prescribing were estimated.
      RESULTS: When the cases were considered individually, the variation in prescribed
      sick leave days was relatively small. However, when considered together,
      variation in prescribing practice became apparent. On average, the overall number
      of days of sick leave prescribed for the entire group of 19 patient cases was
      85.8, varying between 21 and 170 days. The physicians working at a public health
      center and those with more than 20 years experience as an occupational health
      physician tended to prescribe more days of sick leave than others. The quartile
      of physicians who prescribed the fewest days of sick leave would have resulted in
      mean production losses (17,100 euro, 95% CI 16,400-17,700) that were half those
      in the quartile with the most days of sick leave (34,800 euro, 95% CI 33,600
      35,900). CONCLUSIONS: There was variation in the sick leave prescribing practices
      of occupational health care physicians. The most significant factor affecting
      this variation was the health care sector (public, private or employer clinic)
      employing the physicians. Variation in sick leave prescribing patterns can lead
      to inequality between patients.

PMID- 24731597
TI  - Caenorhabditis elegans metabolic gene regulatory networks govern the cellular
      economy.
AB  - Diet greatly impacts metabolism in health and disease. In response to the
      presence or absence of specific nutrients, metabolic gene regulatory networks
      sense the metabolic state of the cell and regulate metabolic flux accordingly,
      for instance by the transcriptional control of metabolic enzymes. Here, we
      discuss recent insights regarding metazoan metabolic regulatory networks using
      the nematode Caenorhabditis elegans as a model, including the modular
      organization of metabolic gene regulatory networks, the prominent impact of diet
      on the transcriptome and metabolome, specialized roles of nuclear hormone
      receptors (NHRs) in responding to dietary conditions, regulation of metabolic
      genes and metabolic regulators by miRNAs, and feedback between metabolic genes
      and their regulators.

PMID- 24731599
TI  - Effects of Artemisia annua and Foeniculum vulgare on chickens highly infected
      with Eimeria tenella (phylum Apicomplexa).
AB  - BACKGROUND: Intensive poultry production systems depend on chemoprophylaxis with
      anticoccidial drugs to combat infection. A floor-pen study was conducted to
      evaluate the anticoccidial effect of Artemisia annua and Foeniculum vulgare on
      Eimeria tenella infection. Five experimental groups were established: negative
      control (untreated, unchallenged); positive control (untreated, challenged); a
      group medicated with 125 ppm lasalocid and challenged; a group medicated with A.
      annua leaf powder at 1.5% in feed and challenged; and a group treated with the
      mixed oils of A. annua and Foeniculum vulgare in equal parts, 7.5% in water and
      challenged. The effects of A. annua and oil extract of A. annua + F. vulgare on
      E. tenella infection were assessed by clinical signs, mortality, fecal oocyst
      output, faeces, lesion score, weight gain, and feed conversion. RESULTS: Clinical
      signs were noticed only in three chickens from the lasalocid group, six from the
      A. annua group, and nine from the A. annua + F. vulgare group, but were present
      in 19 infected chickens from the positive control group. Bloody diarrhea was
      registered in only two chickens from A. annua group, but in 17 chickens from the
      positive control group. Mortality also occurred in the positive control group
      (7/20). Chickens treated with A. annua had a significant reduction in faecal
      oocysts (95.6%; P = 0.027) and in lesion score (56.3%; P = 0.005) when compared
      to the positive control. At the end of experiment, chickens treated with A. annua
      leaf powder had the highest body weight gain (68.2 g/day), after the negative
      control group, and the best feed conversion (1.85) among all experimental groups.
      CONCLUSIONS: Our results suggest that A. annua leaf powder (Aa-p), at 1.5% of the
      daily diet post-infection, can be a valuable alternative for synthetic
      coccidiostats, such as lasalocid.

PMID- 24731600
TI  - The Tinea Hospital in Granada, 1679-1923: an institution with a long history.
AB  - The Tinea hospital in Granada, Spain, was a charitable health facility founded in
      the 17th century and still treating patients well into the 20th century. The
      hospital accepted patients from anywhere, not only those residing in the
      surrounding area. We describe the hospital's founding and the characteristics of
      the patients and caregivers. We also discuss how tinea was considered at the
      time, including the typology and treatment protocols applied as well as diet and
      hygiene measures used. It is striking that a hospital so focused on treating a
      single disease did not produce studies on the condition or on the application of
      contemporary knowledge to guide treatment. 

PMID- 24731601
TI  - Determinants of childhood diarrhea among underfive children in Benishangul Gumuz
      Regional State, North West Ethiopia.
AB  - BACKGROUND: Diarrhea is second only to pneumonia as the cause of child mortality
      worldwide. Developing countries particularly in Sub Saharan Africa including
      Ethiopia have a high burden of this disease. Studies showed that different
      factors were associated with the occurrence of childhood diarrhea. Therefore,
      this study was aimed to identify determinant factors of diarrhea in underfive
      children in Benishangul Gumuz Regional State, western Ethiopia. METHOD:
      Demographic and Health Survey (DHS) data of 2011 was used for this study. The
      data was extracted from the National DHS data using data extraction tools. A
      total of 925 under five children were selected. The logistic regression model was
      employed to examine the determinants of childhood diarrhoea. Both bivariate and
      multivariate data analysis was performed using SPSS version 16.0. RESULT: The
      results of this study indicated that low level of maternal education [AOR = 1.81,
      95% CI (1.12,2.76)], absence of toilet facility [AOR = 3.5, 95% CI (2.4, 5.2)],
      improper child stool disposal methods [AOR = 2.05, 95%CI (1.36, 3.10)], having
      more than two under five children [AOR = 1.73, 95% CI (1.03, 2.93)], higher birth
      order [AOR = 6.1, 95% CI (3.1,12.2)] and the age of children [AOR = 1.9, 95% CI
      (1.2, 3.6)] were found to be the risk factors for childhood diarrhea after
      adjusting for other variables. When toilet facility was stratified by maternal
      education, it showed that children of mothers who had no education were the most
      vulnerable in the absence of toilet facilities [OR = 9.16, 95% CI (5.79, 14.48)].
      CONCLUSION: Under poor environmental conditions, mothers with primary education
      and above protected their children against diarrhea better than mothers with no
      education. Thus, implementing effective educational programs that emphasize
      environmental health and sanitation practices and encouraging female school
      enrolment would reduce childhood diarrheal morbidity in the region.

PMID- 24731602
TI  - Sensory characteristics of chronic non-specific low back pain: a subgroup
      investigation.
AB  - It has been proposed that patients with chronic non-specific low back pain
      (CNSLBP) can be broadly classified based on clinical features that represent
      either predominantly a mechanical pain (MP) or non-mechanical pain (NMP) profile.
      The aim of this study was to establish if patients with CNSLBP who report
      features of NMP demonstrate differences in pain thresholds compared to those who
      report MP characteristics and pain-free controls. This study was a cross
      sectional design investigating whether pressure pain threshold (PPT) and/or cold
      pain threshold (CPT) at three anatomical locations differed between patients with
      mechanical CNSLBP (n = 17) versus non-mechanical CNSLBP (n = 19 and healthy
      controls (n = 19) whilst controlling for confounders. The results of this study
      provide evidence of increased CPT at the wrist in the NMP profile group compared
      to both the MP profile and control subjects, when controlling for gender, sleep
      and depression (NMP versus MP group Odds Ratio (OR): 18.4, 95% confidence
      interval (CI): 2.5-133.1, p = 0.004). There was no evidence of lowered PPT at any
      site after adjustment for confounding factors. Those with an MP profile had
      similar pain thresholds to pain-free controls, whereas the NMP profile group
      demonstrated elevated CPT's consistent with central amplification of pain. These
      findings may represent different pain mechanisms associated with these patient
      profiles and may have implications for targeted management.

PMID- 24731603
TI  - Novel ZnO microflowers on nanorod arrays: local dissolution-driven growth and
      enhanced light harvesting in dye-sensitized solar cells.
AB  - ZnO nanostructures were manipulated, via a low-temperature solution process, from
      pure nanorod arrays to complex nanostructures of microflowers on nanorod arrays
      with adjusted quantities of flowers. We proposed the mechanism of local
      dissolution-driven growth to rationally discuss the novel growth process. These
      nanostructures were used as photoanodes in dye-sensitized solar cells. Compared
      to pure nanorod arrays, the nanorod array-microflower hierarchical structures
      improved the power conversion efficiency from 0.41% to 0.92%, corresponding to a
      124% efficiency increase. The enhancement of the efficiency was mainly ascribed
      to the synergistic effect of the enhanced surface area for higher dye loading and
      the improved light harvesting from efficient light scattering. Present results
      provide a promising route to improve the capability of light-harvesting for ZnO
      nanorod array-based DSSCs. 

PMID- 24731605
TI  - Anatomy and physiology of perforator flaps of the upper limb.
AB  - Perforator flaps are an excellent reconstructive option for a functional upper
      limb reconstruction. This article explores the physiology and general principles
      of perforator flaps and their indications for use in reconstruction of the upper
      extremity. Workhorse perforator flaps of the upper extremity, such as the radial
      artery perforator, ulnar artery perforator, lateral arm perforator, posterior
      interosseous artery, first dorsal metacarpal artery perforator and perforator
      based propeller flaps, are discussed in greater detail. 

PMID- 24731604
TI  - An evolutionary perspective on the history of flap reconstruction in the upper
      extremity.
AB  - Examining the evolution of flap reconstruction of the upper extremity is similar
      to studying the evolution of biological species. This analogy provides a
      perspective to appreciate the contributing factors that led to the development of
      the current arsenal of techniques. It shows the trajectory for the future and
      provides a glimpse of the factors that that will be influential in the future. 

PMID- 24731606
TI  - Local flaps of the hand.
AB  - A local flap consists of skin and subcutaneous tissue that is harvested from a
      site near a given defect while maintaining its intrinsic blood supply. Local skin
      flaps can be a used as a reliable source of soft tissue replacement that replaces
      like with like. Flaps are categorized based on composition, method of transfer,
      flap design, and blood supply, but flap circulation is considered the most
      critical factor for the flap survival. This article reviews the classification of
      local skin flaps of the hand and offers a practical reconstructive approach for
      several soft tissue defects of the hand and digits. 

PMID- 24731607
TI  - Flap reconstruction of the elbow and forearm: a case-based approach.
AB  - Elbow and forearm wounds have distinct reconstructive requirements, but both
      require a durable and pliable solution. Pedicle, free fasciocutaneous and muscle,
      and distant (2-stage) flaps have a role in wound reconstruction in these unique
      areas. This article presents practical surgical cases as a guide to soft tissue
      reconstruction of the elbow and forearm. 

PMID- 24731608
TI  - Free muscle flaps for reconstruction of upper limb defects.
AB  - Restoration of structure, function, and sensation are critical after trauma or
      tumor resection of the hand. Thorough debridement, reconstruction of functional
      structures, and immediate soft tissue coverage are most effectively performed in
      a single stage within approximately 24 hours of the injury. Skin flaps provide
      robust, pliable, and cosmetically appropriate tissue that is not prone to
      contracture and that facilitates secondary reconstructive work. Muscle flaps
      retain indications for complex defects with substantial initial contamination or
      dead space, or for reanimation. In this article, the indications, options, and
      surgical techniques for free muscle flap reconstruction of upper limb defects are
      reviewed. 

PMID- 24731609
TI  - Indications, selection, and use of distant pedicled flap for upper limb
      reconstruction.
AB  - Despite the inherent advantages of free flaps for soft tissue cover in upper limb
      reconstruction, pedicled flaps remain the workhorse in many centers worldwide.
      Presumed disadvantages of pedicled flaps are that it requires multiple stages,
      longer hospital stay, are bulky, and primary reconstruction of composite defects
      cannot be done. Refinements in technique during planning can offset many of the
      disadvantages. Pedicled flaps are quick and easy to raise and do not need any
      special microsurgical expertise. Where free flaps are not possible or they fail,
      pedicled flaps are the lifeboat. An upper limb reconstructive surgeon must be
      adept at performing these flaps in challenging situations. 

PMID- 24731610
TI  - Free skin flap coverage of the upper extremity.
AB  - Successful soft tissue reconstruction of the upper extremity must provide stable
      coverage and restore function to the injured hand. To ensure the best possible
      outcome after traumatic upper extremity injuries, early radical debridement and
      early flap coverage that restores all missing tissue components is critical to
      allow early mobilization. Free flaps provide extraordinary versatility in
      reconstructing defects of soft tissue, muscle, tendon, and bone. 

PMID- 24731611
TI  - Refinements and secondary surgery after flap reconstruction of the traumatized
      hand.
AB  - The traumatized hand often has soft tissue loss requiring flap reconstruction.
      Before proceeding with flap selection, the need for future refinement and
      secondary surgery should be taken into consideration. Although muscle flaps may
      offer better contour, fasciocutaneous flaps allow easier secondary flap
      elevation. After the initial flap reconstruction, indications for secondary
      procedures may be managed according to tissue type: bone, joint, tendon, nerve,
      and soft tissue. 

PMID- 24731612
TI  - Optimizing functional and aesthetic outcomes of upper limb soft tissue
      reconstruction.
AB  - This article highlights reconstructive principles in flap selection, use, and
      insetting to optimize functional and aesthetic outcomes after upper extremity
      reconstruction. The concept of respecting the aesthetic units of the hand during
      reconstruction is discussed. A current literature review of the aesthetic
      outcomes using various flaps, such as fasciocutaneous, fascia only, and muscle
      flaps, is provided. An approach based on aesthetic unit principles to upper
      extremity reconstruction is also highlighted to help optimize outcomes. 

PMID- 24731614
TI  - Preface. Flap reconstruction of the traumatized upper extremity.

PMID- 24731613
TI  - Dermal skin substitutes for upper limb reconstruction: current status,
      indications, and contraindications.
AB  - Dermal skin substitutes are a group of biologically engineered materials composed
      of collagen and glycosaminoglycans and are devoid of cellular structures. These
      biodegradable materials act as an artificial dermis to promote neovascularization
      and neodermis formation. Their applications in soft tissue reconstructions are
      rapidly expanding. In this article, the indications, advantages, and limitations
      of dermal skin substitutes for reconstruction of soft tissue defects of the upper
      extremity are reviewed. 

PMID- 24731615
TI  - "How can I still be me?": Strategies to maintain a sense of self in the context
      of a neurological condition.
AB  - The Living with a Neurological Condition (LINC) study was part of the National
      Population Health Study of Neurological Conditions conducted in Canada. This
      article describes empirical original qualitative data collected in the third and
      final phase of this study and examines how individuals living with a neurological
      condition maintain continuity of their sense of self, with a particular focus on
      their strategies. Fifteen interviews were analysed for this paper. Emerging
      strategies for maintaining sense of self include: (1) avoidance and denial, (2)
      cognitive reframing, (3) articulation of the self through imagined positive
      identity, (4) strategies that reconnect to identity in the past, (5) adjusting
      and altering goals, (6) spiritual activities, (7) humour, (8) comparison with
      others: identity as shaped through social constructs, and (9) creating
      communities: a reciprocal reflection of self. 

PMID- 24731617
TI  - Identifying aspects of neighbourhood deprivation associated with increased
      incidence of schizophrenia.
AB  - BACKGROUND: Several studies have found an association between area deprivation
      and incidence of schizophrenia. However, not all studies have concurred and
      definitions of deprivation have varied between studies. Relative deprivation and
      inequality seem to be particularly important, but which aspects of deprivation or
      how this effect might operate is not known. METHODS: The Lambeth Early Onset case
      register is a database of all cases of first episode psychosis aged 16 to 35years
      from the London Borough of Lambeth, a highly urban area. We identified 405 people
      with first onset schizophrenia who presented between 2000 and 2007. We calculated
      the overall incidence of first onset schizophrenia and tested for an association
      with area-level deprivation, using a multi-domain index of deprivation (IMD
      2004). Specific analyses into associations with individual sub-domains of
      deprivation were then undertaken. RESULTS: Incidence rates, directly standardized
      for age and gender, were calculated for Lambeth at two geographical levels (small
      and large neighbourhood level). The Poisson regression model predicting incidence
      rate ratios for schizophrenia using overall deprivation score was statistically
      significant at both levels after adjusting for ethnicity, ethnic density,
      population density and population turnover. The incidence rate ratio for
      electoral ward deprivation was 1.03 (95% CI=1.004-1.04) and for the super output
      area deprivation was 1.04 (95% CI=1.02-1.06). The individual domains of crime,
      employment deprivation and educational deprivation were statistically significant
      predictors of incidence but, after adjusting for the other domains as well as
      age, gender, ethnicity and population density, only crime and educational
      deprivation, remained statistically significant. Low income, poor housing and
      deprived living environment did not predict incidence. CONCLUSIONS: In a highly
      urban area, an association was found between area-level deprivation and incidence
      of schizophrenia, after controlling for age, gender, ethnicity and population
      density; high crime and low levels of education accounted for this. As both of
      these are potentially modifiable, this suggests a possible means to reduce the
      incidence of schizophrenia.

PMID- 24731616
TI  - A systematic review of shared decision making interventions in chronic
      conditions: a review protocol.
AB  - BACKGROUND: Chronic conditions are a major source of morbidity, mortality and
      cost worldwide. Shared decision making is one way to improve care for patients
      with chronic conditions. Although it has been widely studied, the effect of
      shared decision making in the context of chronic conditions is unknown.
      METHODS/DESIGN: We will perform a systematic review with the objective of
      determining the effectiveness of shared decision making interventions for persons
      diagnosed with chronic conditions. We will search the following databases for
      relevant articles: PubMed, Scopus, Ovid MEDLINE, Ovid EMBASE, Ovid EBM Reviews
      CENTRAL, CINAHL, and Ovid PsycInfo. We will also search clinical trial registries
      and contact experts in the field to identify additional studies. We will include
      randomized controlled trials studying shared decision making interventions in
      patients with chronic conditions who are facing an actual decision. Shared
      decision making interventions will be defined as any intervention aiming to
      facilitate or improve patient and/or clinician engagement in a decision making
      process. We will describe all studies and assess their quality. After adjusting
      for missing data, we will analyze the effect of shared decision making
      interventions on outcomes in chronic conditions overall and stratified by
      condition. We will evaluate outcomes according to an importance ranking informed
      by a variety of stakeholders. We will perform several exploratory analyses
      including the effect of author contact on the estimates of effect. DISCUSSION: We
      anticipate that this systematic review may have some limitations such as
      heterogeneity and imprecision; however, the results will contribute to improving
      the quality of care for individuals with chronic conditions and facilitate a
      process that allows decision making that is most consistent with their own values
      and preferences. TRIAL REGISTRATION: PROSPERO Registration Number:
      CRD42013005784.

PMID- 24731618
TI  - Memory self-efficacy in schizophrenia.
AB  - The positive association between memory self-efficacy (MSE), defined as the
      beliefs about one's ability to use memory effectively, and memory performance is
      highly documented in the literature but has not yet been explored in
      schizophrenia. In the current study the relationship between MSE and objective
      memory measures was explored in thirty schizophrenia patients and twenty healthy
      controls. Compared to healthy controls, schizophrenia patients presented lower
      MSE, which was associated with depression. Among controls, but not patients, MSE
      was positively related to memory performance. This result suggests that normal
      relationship between MSE and memory functioning is disrupted in schizophrenia. 

PMID- 24731619
TI  - The effects of individually tailored formulation-based cognitive behavioural
      therapy in auditory hallucinations and delusions: a meta-analysis.
AB  - There is no meta-analysis of cognitive behavioural therapy for delusions and
      hallucinations separately. The aim of this meta-analysis is to evaluate the end
      of-treatment effects of individually tailored case-formulation cognitive
      behavioural therapy on delusions and auditory hallucinations using symptom
      specific outcome measures. A systematic search of the trial literature was
      conducted in MEDLINE, PSYCHINFO and EMBASE. Eighteen studies were selected with
      symptom specific outcome measures. Hedges' g was computed and outcomes were
      pooled meta-analytically using the random-effects model. Our main analyses were
      with the selected studies with CBT using individually tailored case-formulation
      that aimed to reduce hallucinations and delusions. The statistically significant
      effect-sizes were 0.36 with delusions and 0.44 with hallucinations, which are
      modest and in line with other recent meta-analyses. Contrasted with active
      treatment, CBT for delusions lost statistical significance (0.33), but the effect
      size for CBT for hallucinations increased (0.49). Blinded studies reduced effect
      size in delusions (0.24) and gained some in hallucinations (0.46). There was no
      heterogeneity in hallucinations and moderate heterogeneity in delusion trials. We
      conclude that CBT is effective in treating auditory hallucinations. CBT for
      delusions is also effective, but the results must be interpreted with caution,
      because of heterogeneity and the non-significant effect-sizes when compared with
      active treatment. 

PMID- 24731620
TI  - Impaired facilitation of self-control cognition by glucose in patients with
      schizophrenia: a randomized controlled study.
AB  - OBJECTIVE: Studies in healthy individuals show that exerting self-control
      consumes cognitive resources, which reduces subsequent self-control performance.
      Restoring the availability of blood glucose eliminates this impairment. Patients
      with schizophrenia are found to have self-regulatory dysfunctions. This study
      aims to investigate whether patient's (a) glucose facilitation effects will be
      impaired, and (b) will have exaggerated depletion in a self-control task. METHOD:
      40 patients with schizophrenia-spectrum disorders and 40 normal controls were
      recruited. A two drinks (glucose vs. placebo)*two depleting phases (self-control
      depleted vs. non-depleted) between-groups design was used. We examined the blood
      glucose levels before and after the selfcontrol depletion phase and the
      subsequent performances in two self-control tasks (handgrip and Stroop tests)
      after the drink condition. RESULTS: The four groups (depleting*glucose,
      depleting*placebo, non-depleting*glucose and nondepleting*placebo) of both
      patients and normal controls were comparable on a number of characteristics. The
      change in blood glucose level in the depleting group was significantly different
      from those in the non-depleting group. Two*two between-subjects ANOVAs were
      carried out to test the performances in the handgrip and Stroop tasks.
      Significant interactions were found in healthy controls regarding both tasks.
      However, a significant interaction was only found in patients regarding the
      handgrip task but not the Stroop task. CONCLUSIONS: This study demonstrated an
      abnormal glucose facilitation effect in patients during a cognitive self-control
      task but not during a physical self-control task. The findings also suggested for
      the first time that a self-control depletion effect is intact in patients with
      schizophrenia.

PMID- 24731621
TI  - Analysis of amino acid composition in proteins of animal tissues and foods as pre
      column o-phthaldialdehyde derivatives by HPLC with fluorescence detection.
AB  - Studies of protein nutrition and biochemistry require reliable methods for
      analysis of amino acid (AA) composition in polypeptides of animal tissues and
      foods. Proteins are hydrolyzed by 6M HCl (110 degrees C for 24h), 4.2M NaOH (105
      degrees C for 20 h), or proteases. Analytical techniques that require high
      performance liquid chromatography (HPLC) include pre-column derivatization with 4
      chloro-7-nitrobenzofurazan, 9-fluorenyl methylchloroformate,
      phenylisothiocyanate, naphthalene-2,3-dicarboxaldehyde, 6-aminoquinolyl-N
      hydroxysuccinimidyl carbamate, and o-phthaldialdehyde (OPA). OPA reacts with
      primary AA (except cysteine or cystine) in the presence of 2-mercaptoethanol or 3
      mercaptopropionic acid to form a highly fluorescent adduct. OPA also reacts with
      4-amino-1-butanol and 4-aminobutane-1,3-diol produced from oxidation of proline
      and 4-hydroxyproline, respectively, in the presence of chloramine-T plus sodium
      borohydride at 60 degrees C, or with S-carboxymethyl-cysteine formed from
      cysteine and iodoacetic acid at 25 degrees C. Fluorescence of OPA derivatives is
      monitored at excitation and emission wavelengths of 340 and 455 nm, respectively.
      Detection limits are 50 fmol for AA. This technique offers the following
      advantages: simple procedures for preparation of samples, reagents, and mobile
      phase solutions; rapid pre-column formation of OPA-AA derivatives and their
      efficient separation at room temperature (e.g., 20-25 degrees C); high
      sensitivity of detection; easy automation on the HPLC apparatus; few interfering
      side reactions; a stable chromatography baseline for accurate integration of peak
      areas; and rapid regeneration of guard and analytical columns. Thus, the OPA
      method provides a useful tool to determine AA composition in proteins of animal
      tissues (e.g., skeletal muscle, liver, intestine, placenta, brain, and body
      homogenates) and foods (e.g., milk, corn grain, meat, and soybean meal).

PMID- 24731622
TI  - A method superior to adding percentiles when only limited anthropometric data
      such as percentile tables are available for design models.
AB  - PURPOSE: Designers and ergonomists may occasionally be limited to using tables of
      percentiles of anthropometric data to model users. Design models that add or
      subtract percentiles produce unreliable estimates of the proportion of users
      accommodated, in part because they assume a perfect correlation between
      variables. Percentile data do not allow the use of more reliable modeling methods
      such as Principle Component Analysis. A better method is needed. RESULTS: A new
      method for modeling with limited data is described. It uses measures of central
      tendency (median or mean) of the range of possible correlation values to estimate
      the combined variance is shown to reduce error compared to combining percentiles.
      Second, use of the Chebyshev inequality allows the designer to more reliably
      estimate the percent accommodation when the distributions of the underlying
      anthropometric data are unknown than does combining percentiles. CONCLUSION: This
      paper describes a modeling method that is more accurate than combining
      percentiles when only limited data are available.

PMID- 24731623
TI  - Improving access to emergent spinal care through knowledge translation: an
      ethnographic study.
AB  - BACKGROUND: For patients and family members, access to timely specialty medical
      care for emergent spinal conditions is a significant stressor to an already
      serious condition. Timing to surgical care for emergent spinal conditions such as
      spinal trauma is an important predictor of outcome. However, few studies have
      explored ethnographically the views of surgeons and other key stakeholders on
      issues related to patient access and care for emergent spine conditions. The
      primary study objective was to determine the challenges to the provision of
      timely care as well as to identify areas of opportunities to enhance care
      delivery. METHODS: An ethnographic study of key administrative and clinical care
      providers involved in the triage and care of patients referred through CritiCall
      Ontario was undertaken utilizing standard methods of qualitative inquiry. This
      comprised 21 interviews with people involved in varying capacities with the
      provision of emergent spinal care, as well as qualitative observations on an
      orthopaedic/neurosurgical ward, in operating theatres, and at CritiCall Ontario's
      call centre. RESULTS: Several themes were identified and organized into
      categories that range from inter-professional collaboration through to issues of
      hospital-level resources and the role of relationships between hospitals and
      external organizations at the provincial level. Underlying many of these issues
      is the nature of the medically complex emergent spine patient and the scientific
      evidentiary base upon which best practice care is delivered. Through the
      implementation of knowledge translation strategies facilitated from this
      research, a reduction of patient transfers out of province was observed in the
      one-year period following program implementation. CONCLUSIONS: Our findings
      suggest that competing priorities at both the hospital and provincial level
      create challenges in the delivery of spinal care. Key stakeholders recognized
      spinal care as aligning with multiple priorities such as emergent/critical care,
      medical through surgical, acute through rehabilitative, disease-based (i.e.
      trauma, cancer), and wait times initiatives. However, despite newly implemented
      strategies, there continues to be increasing trends over time in the number of
      spinal CritiCall Ontario referrals. This reinforces the need for ongoing inter
      professional efforts in care delivery that take into account the institutional
      contexts that may constrain individual or team efforts.

PMID- 24731624
TI  - Denaverine hydrochloride and carbetocin increased welfare during and after
      parturition and enhanced subsequent fertility in cattle.
AB  - The objectives of the current study were to investigate the influence of
      denaverine hydrochloride and carbetocin on softening and dilatation of the birth
      canal, the need for assistance during parturition, calf mortality, retention of
      fetal membranes, endometritis, and subsequent fertility. Altogether 200 animals
      (100 cows and 100 heifers) of the Simmental breed were divided into 2 groups:
      treatment (n = 100) and control (n = 100). Animals in the treatment group
      received denaverine hydrochloride and carbetocin (a maximum of twice for each,
      depending on the progression of labor) during delivery over a maximum of 4
      waiting periods (30 min each), whereas control animals experienced the same
      waiting periods but received no treatment. The treatment protocol had a positive
      influence on the ease of calving and postpartum reproductive health. The
      treatment increased the number of animals with the birth canal dilated by more
      than 25 cm, and halved the need for any assistance at parturition. In addition,
      treatment decreased the occurrence of difficult calving, the need for episiotomy,
      the appearance of birth canal lesions, and clinical endometritis. The treatment
      protocol had an effect throughout the entire puerperal period, as treated animals
      conceived with fewer artificial inseminations (1.3 vs. 1.6 artificial
      inseminations/pregnancy) and sooner (67 vs. 78 d open) compared with control
      animals. Denaverine hydrochloride and carbetocin administered in combination
      during parturition affected the progression and ease of calving, and thus the
      welfare of cows in labor and subsequently. However, further studies are needed to
      confirm the findings and to establish best practices.

PMID- 24731625
TI  - Insulin stimulates glucose uptake via a phosphatidylinositide 3-kinase-linked
      signaling pathway in bovine mammary epithelial cells.
AB  - The aim of this study was to investigate the effects of insulin on glucose uptake
      in lactating bovine mammary epithelial cells (BMEC). Primary BMEC were cultured
      in Dulbecco's modified Eagle's medium/nutrient mixture F-12 and treated with
      different levels of insulin (0, 5, 50, and 500 ng/mL) for 48 h after a 24-h
      starvation without fetal calf serum. Compared with the control cells (0 ng of
      insulin/mL), cell proliferation was enhanced by insulin treatment at all tested
      levels. Insulin significantly increased glucose uptake at a concentration of 500
      ng/mL. In addition, the protein synthesis inhibitor cycloheximide (0.5mg/mL)
      counteracted the insulin-elevated glucose uptake, thereby suggesting that newly
      synthesized transporter protein might take part in the insulin-induced glucose
      uptake. Furthermore, pretreatment of the cells with SB203580, an inhibitor of p38
      mitogen-activated protein kinase, did not influence the insulin-induced glucose
      uptake, but LY294002, a specific inhibitor of phosphatidylinositide 3-kinase,
      significantly reduced the insulin-stimulated glucose uptake. These results
      indicated that insulin-induced glucose uptake in BMEC may involve the
      phosphatidylinositide 3-kinase- but not mitogen-activated protein kinase-mediated
      signaling pathways.

PMID- 24731626
TI  - Effects of hydroxy trace minerals on oxidative metabolism, cytological
      endometritis, and performance of transition dairy cows.
AB  - Multiparous Holstein cows (n=60) were used to determine effects of supplementing
      hydroxy forms of Zn, Cu, and Mn compared with 2 other common supplementation
      strategies on oxidative metabolism, cytological endometritis, and performance of
      transition cows. After a 1-wk pretreatment period, cows were assigned randomly to
      1 of 3 dietary treatments from 21 d before expected calving through 84 d
      postcalving. Dietary treatments administered by daily top-dressing included (1)
      inorganic sulfate forms of Zn, Cu, and Mn (ITM); (2) a blend (75:25) of sulfates
      and organic complexes of Zn, Cu, and Mn (ITM/OTM); and (3) hydroxy trace minerals
      (HTM) of Zn, Cu, and Mn. The resulting dietary concentrations of supplemental Zn,
      Cu, and Mn were similar among treatments and averaged 40, 10, and 27 mg/kg,
      respectively, before calving and 59, 15, and 40 mg/kg, respectively, after
      calving. Total concentrations of Zn, Cu, and Mn averaged 80, 16, and 62 mg/kg
      during the prepartum period and 102, 23, and 75 mg/kg, respectively, during the
      postpartum period. Overall, effects of treatment on milk yield and milk
      composition were not significant. Cows fed HTM during the prepartum period had
      higher body weight (BW) than those fed ITM during the prepartum period and had
      higher BW during the postpartum period than those fed the other treatments;
      however, BW change, body condition score, and body condition score change were
      not affected by treatment. Plasma total antioxidant capacity was lower in cows
      fed HTM than ITM but was not different from cows fed ITM/OTM. Cows fed HTM tended
      to have lower concentrations of plasma thiobarbituric acid reactive substances
      than those fed ITM during the whole study period, but plasma thiobarbituric acid
      reactive substances were not different between HTM and ITM/OTM. Plasma
      haptoglobin was lower in cows fed HTM than ITM/OTM at 1 wk postpartum.
      Endometrial cytology 7d postcalving and cytological endometritis as assessed on
      1d between 40 and 60 d postcalving was not affected by treatment. In conclusion,
      supplementation with HTM sources of Zn, Cu, and Mn modulated plasma variables
      related to oxidative metabolism compared with supplementation with ITM; however,
      HTM and ITM/OTM resulted in similar responses. Furthermore, the source of trace
      minerals did not affect performance or uterine health in this experiment.

PMID- 24731627
TI  - International genetic evaluations for feed intake in dairy cattle through the
      collation of data from multiple sources.
AB  - Feed represents a large proportion of the variable costs in dairy production
      systems. The omission of feed intake measures explicitly from national dairy cow
      breeding objectives is predominantly due to a lack of information from which to
      make selection decisions. However, individual cow feed intake data are available
      in different countries, mostly from research or nucleus herds. None of these data
      sets are sufficiently large enough on their own to generate accurate genetic
      evaluations. In the current study, we collate data from 10 populations in 9
      countries and estimate genetic parameters for dry matter intake (DMI). A total of
      224,174 test-day records from 10,068 parity 1 to 5 records of 6,957 cows were
      available, as well as records from 1,784 growing heifers. Random regression
      models were fit to the lactating cow test-day records and predicted feed intake
      at 70 d postcalving was extracted from these fitted profiles. The random
      regression model included a fixed polynomial regression for each lactation
      separately, as well as herd-year-season of calving and experimental treatment as
      fixed effects; random effects fit in the model included individual animal
      deviation from the fixed regression for each parity as well as mean herd-specific
      deviations from the fixed regression. Predicted DMI at 70 d postcalving was used
      as the phenotype for the subsequent genetic analyses undertaken using an animal
      repeatability model. Heritability estimates of predicted cow feed intake 70 d
      postcalving was 0.34 across the entire data set and varied, within population,
      from 0.08 to 0.52. Repeatability of feed intake across lactations was 0.66.
      Heritability of feed intake in the growing heifers was 0.20 to 0.34 in the 2
      populations with heifer data. The genetic correlation between feed intake in
      lactating cows and growing heifers was 0.67. A combined pedigree and genomic
      relationship matrix was used to improve linkages between populations for the
      estimation of genetic correlations of DMI in lactating cows; genotype information
      was available on 5,429 of the animals. Populations were categorized as North
      America, grazing, other low input, and high input European Union. Albeit
      associated with large standard errors, genetic correlation estimates for DMI
      between populations varied from 0.14 to 0.84 but were stronger (0.76 to 0.84)
      between the populations representative of high-input production systems. Genetic
      correlations with the grazing populations were weak to moderate, varying from
      0.14 to 0.57. Genetic evaluations for DMI can be undertaken using data collated
      from international populations; however, genotype-by-environment interactions
      with grazing production systems need to be considered.

PMID- 24731628
TI  - Performance of dairy cows fed silage and grain produced from second-generation
      insect-protected (Bacillus thuringiensis) corn (MON 89034), compared with
      parental line corn or reference corn.
AB  - Corn grain and corn silage are major feed components in lactating dairy cow
      rations. Bacillus thuringiensis (B.t.) is a naturally occurring soil bacterium
      that produces a protein that is toxic to lepidopteran insects that may damage
      plant tissues and reduce corn quality and yields. During each of the four 28-d
      periods, cows were offered 1 of 4 rations in which the corn grain and silage
      originated from different corn hybrids: a nontransgenic corn control (from hybrid
      DKC63-78; Monsanto Co., St. Louis, MO), a B.t. test substance corn (MON 89034 in
      hybrid DKC63-78; Monsanto Co.), and 2 commercial nontransgenic reference (Ref)
      hybrids: DKC61-42 (Ref 1) and DKC62-30 (Ref 2; Monsanto Co.). Sixteen multiparous
      Holstein cows averaging 110 +/- 21 d in milk and weighing 684 +/- 62.3 kg were
      blocked by days in milk and milk yield and randomly assigned to one of four 4 * 4
      Latin squares. Diets were formulated to contain 36.4% corn silage and 16.3% corn
      grain. Dry matter intake was greater for cows consuming B.t. corn (26.6 +/- 0.59
      kg/d) compared with the control, Ref 1, and Ref 2 corn diets (25.4, 25.0, and
      25.6 +/- 0.59 kg/d, respectively). Milk yield, fat yield, and percentage of fat
      (36.8 +/- 0.98 kg/d, 1.22 +/- 0.05 kg/d, and 3.3 +/- 0.10%), milk protein yield
      and percentage of protein (1.11 +/- 0.03 kg/d and 3.01 +/- 0.05%), milk urea
      nitrogen concentration (14.01 +/- 0.49 mg/dL), and 3.5% fat-corrected milk yield
      (35.7 +/- 1.07 kg/d) were not different across treatments. The results from this
      study show that lactating dairy cows that consume B.t. corn (MON 89034) do not
      differ from lactating dairy cows that consume nontransgenic corn in milk yield,
      3.5% fat-corrected milk per unit of dry matter intake, or milk components.

PMID- 24731629
TI  - A stochastic frontier approach to study the relationship between gastrointestinal
      nematode infections and technical efficiency of dairy farms.
AB  - The impact of gastrointestinal (GI) nematode infections in dairy farming has
      traditionally been assessed using partial productivity indicators. But such
      approaches ignore the impact of infection on the performance of the whole farm.
      In this study, efficiency analysis was used to study the association of the GI
      nematode Ostertagia ostertagi on the technical efficiency of dairy farms. Five
      years of accountancy data were linked to GI nematode infection data gained from a
      longitudinal parasitic monitoring campaign. The level of exposure to GI nematodes
      was based on bulk-tank milk ELISA tests, which measure the antibodies to O.
      ostertagi and was expressed as an optical density ratio (ODR). Two unbalanced
      data panels were created for the period 2006 to 2010. The first data panel
      contained 198 observations from the Belgian Farm Accountancy Data Network
      (Brussels, Belgium) and the second contained 622 observations from the Boerenbond
      Flemish farmers' union (Leuven, Belgium) accountancy system (Tiber Farm
      Accounting System). We used the stochastic frontier analysis approach and defined
      inefficiency effect models specified with the Cobb-Douglas and transcendental
      logarithmic (Translog) functional form. To assess the efficiency scores, milk
      production was considered as the main output variable. Six input variables were
      used: concentrates, roughage, pasture, number of dairy cows, animal health costs,
      and labor. The ODR of each individual farm served as an explanatory variable of
      inefficiency. An increase in the level of exposure to GI nematodes was associated
      with a decrease in technical efficiency. Exposure to GI nematodes constrains the
      productivity of pasture, health, and labor but does not cause inefficiency in the
      use of concentrates, roughage, and dairy cows. Lowering the level of infection in
      the interquartile range (0.271 ODR) was associated with an average milk
      production increase of 27, 19, and 9L/cow per year for Farm Accountancy Data
      Network farms and 63, 49, and 23L/cow per year for Tiber Farm Accounting System
      farms in the low- (0-90), medium- (90-95), and high- (95-99) efficiency score
      groups, respectively. The potential milk increase associated with reducing the
      level of infection was higher for highly efficient farms (6.7% of the total
      possible milk increase when becoming fully technically efficient) than for less
      efficient farms (3.8% of the total possible milk increase when becoming fully
      technically efficient). 

PMID- 24731630
TI  - Rumination time around calving: an early signal to detect cows at greater risk of
      disease.
AB  - The main objective of this experiment was to evaluate the use of rumination time
      (RT) during the peripartum period as a tool for early disease detection. The
      study was carried out in an experimental freestall barn and involved 23 Italian
      Friesian cows (9 primiparous and 14 multiparous). The RT was continuously
      recorded by using an automatic system (Hr-Tag, SCR Engineers Ltd., Netanya,
      Israel), and data were summarized in 2-h intervals. Blood samples were collected
      from 30 d before calving to 42 d in milk (DIM) to assess biochemical indicators
      related to energy, protein, and mineral metabolism, as well as markers of
      inflammation and some enzyme activities. The liver functionality index, which
      includes some negative acute-phase proteins and related parameters (albumin,
      cholesterol, and bilirubin), was used to evaluate the severity of inflammatory
      conditions occurring around calving. The cows were retrospectively categorized
      according to RT observed between 3 and 6 DIM into those with the lowest (L) and
      highest (H) RT. The average RT before calving (-20 to -2d) was 479 min/d (range
      264 to 599), reached a minimum value at calving (30% of RT before calving), and
      was nearly stable after 15 DIM (on average 452 min/d). Milk yield in early
      lactation (on average 26.8 kg/d) was positively correlated with RT (r = 0.33).
      After calving, compared with H cows, the L cows had higher values of haptoglobin
      (0.61 and 0.34 g/L at 10 DIM in L and H, respectively) for a longer time, had a
      greater increase in total bilirubin (9.5 and 5.7 MUmol/L at 5 DIM in L and H),
      had greater reductions of albumin (31.2 and 33.5 g/L at 10 DIM in L and H) and
      paraoxonase (54 and 76 U/ml at 10 DIM in L and H), and had a slower increase of
      total cholesterol (2.7 and 3.2 mmol/L at 20 DIM in L and H). Furthermore, a lower
      average value of liver functionality index was observed in L (-6.97) compared
      with H (-1.91) cows. These results suggest that severe inflammation around
      parturition is associated with a slower increase of RT after calving.
      Furthermore, more than 90% of the cows in the L group had clinical diseases in
      early lactation compared with 42% of the H cows. Overall, our results demonstrate
      the utility of monitoring RT around calving, and in particular during the first
      week of lactation, as a way to identify in a timely fashion those cows at a
      greater risk of developing a disease in early lactation.

PMID- 24731631
TI  - Early warnings from automatic milk yield monitoring with online synergistic
      control.
AB  - Sensors play a crucial role in the future of dairy farming. Modern dairy farms
      today are equipped with many different sensors for milk yield, body weight,
      activity, and even milk composition. The challenge, however, is to translate
      signals from these sensors into relevant information for the farmer. Because the
      measured values for an individual cow show nonstationary behavior, the concepts
      of statistical process control, which are commonly used in industry, cannot be
      used directly. The synergistic control concept overcomes this problem by on-line
      (real-time) modeling of the process and application of statistical process
      control to the residuals between the measured and modeled values. In this study,
      the synergistic control concept was developed and tested for early detection of
      anomalies in dairy cows based on detection of shifts in milk yield. Compared with
      the combination of visual observation and milk conductivity measurements, the
      developed strategy had a sensitivity of 63% for detecting clinical mastitis.
      Consequently, this technique could have added value on many farms, as it extracts
      practical information out of inexpensive data that are already available. As it
      can be easily extended to other measured parameters, the technique shows
      potential for early detection of other nutrition and health problems. 

PMID- 24731632
TI  - Lactoferrin protects against chemical-induced rat liver fibrosis by inhibiting
      stellate cell activation.
AB  - Liver diseases, which can be caused by alcohol abuse, chemical intoxication,
      viral hepatitis infection, and autoimmune disorders, are a significant health
      issue because they can develop into liver fibrosis and cirrhosis. Lactoferrin
      (LF), a siderophilic protein with 2 iron-binding sites, has been demonstrated to
      possess a multitude of biological functions, including antiinflammation,
      anticancer, and antimicrobial effects, as well as immunomodulatory-enhancing
      functions. In the current study, we induced hepatotoxicity in rats with
      dimethylnitrosamine (DMN) to establish a situation that would enable us to
      evaluate the hepatoprotective effects of LF against hepatic injury. Our results
      showed that DMN-induced hepatic pathological damage significantly decreased the
      body weight and liver index, increased the mRNA and protein levels of collagen
      alpha-1(I) (ColIalpha-1) and alpha-smooth muscle actin, and increased the
      hydroxyproline content. However, treatment with LF significantly increased body
      weight and liver index, decreased the mRNA and protein levels of ColIalpha-1 and
      alpha-smooth muscle actin, and suppressed the hydroxyproline content when
      compared with the DMN-treated group. Liver histopathology also showed that low
      dose LF (100mg/kg of body weight) or high-dose LF (300 mg/kg of body weight)
      could significantly reduce the incidences of liver lesions induced by DMN. These
      results suggest that the LF exhibits potent hepatoprotection against DMN-induced
      liver damage in rats and that the hepatoprotective effects of LF may be due to
      the inhibition of collagen production and to stellate cell activation.

PMID- 24731633
TI  - Random regression test-day model for clinical mastitis: genetic parameters, model
      comparison, and correlations with indicator traits.
AB  - The objective was to study genetic (co)variance components for binary clinical
      mastitis (CM), test-day protein yield, and udder health indicator traits [test
      day somatic cell score (SCS) and type traits of the udder composite] in the
      course of lactation with random regression models (RRM). The study used a data
      set from selected 15 large-scale contract herds including 26,651 Holstein cows.
      Test-day production and CM data were recorded from 2007 to 2012 and comprised
      parities 1 to 3. A longitudinal CM data structure was generated by assigning CM
      records to adjacent official test dates. Bivariate threshold-linear RRM were
      applied to estimate genetic (co)variance components between longitudinal binary
      CM (0 = healthy; 1 = diseased) and longitudinal Gaussian distributed protein
      yield and SCS test-day data. Heritabilities for liability to CM (heritability
      ~0.15 from 0 to 305 d after calving) were slightly higher than for SCS for
      corresponding days in milk (DIM) in the course of lactation. Daily genetic
      correlations between CM and SCS were moderate to high (genetic correlation
      ~0.70), but substantially decreased at the very end of lactation. Genetic
      correlations between CM at different test days were close to 1 for adjacent test
      days, but were close to zero for test days far apart. Daily genetic correlations
      between CM and protein yield were low to moderate. For identical DIM (e.g., DIM
      20, 160, and 300), genetic correlations were -0.03, 0.11, and 0.18, respectively,
      and disproved pronounced genetic antagonisms between udder health and
      productivity. Correlations between estimated breeding values (EBV) for CM from
      the RRM and official EBV for linear type traits of the udder composite, including
      EBV from 74 influential sires (sires with >60 daughters), were -0.31 for front
      teat placement, -0.01 for rear teat placement, -0.31 for fore udder attachment, 
      0.32 for udder depth, and -0.08 for teat length. Estimated breeding values for CM
      from the RRM were compared with EBV from a multiple-trait model and with EBV from
      a repeatability model. For test days covering an identical time span and on a
      lactation level, correlations between EBV from RRM, multiple-trait model, and
      repeatability model were close to 1. Most relevant results suggest the routine
      application of threshold RRM to binary CM to (1) allow selection of genetically
      superior sires for distinct stages of lactation and (2) achieve higher selection
      response in CM compared with selection strategies based on indicator type traits
      or based on the indicator-trait SCS.

PMID- 24731634
TI  - Comparison of modelling techniques for milk-production forecasting.
AB  - The objective of this study was to assess the suitability of 3 different modeling
      techniques for the prediction of total daily herd milk yield from a herd of 140
      lactating pasture-based dairy cows over varying forecast horizons. A nonlinear
      auto-regressive model with exogenous input, a static artificial neural network,
      and a multiple linear regression model were developed using 3 yr of historical
      milk-production data. The models predicted the total daily herd milk yield over a
      full season using a 305-d forecast horizon and 50-, 30-, and 10-d moving
      piecewise horizons to test the accuracy of the models over long- and short-term
      periods. All 3 models predicted the daily production levels for a full lactation
      of 305 d with a percentage root mean square error (RMSE) of <= 12.03%. However,
      the nonlinear auto-regressive model with exogenous input was capable of
      increasing its prediction accuracy as the horizon was shortened from 305 to 50,
      30, and 10 d [RMSE (%)=8.59, 8.1, 6.77, 5.84], whereas the static artificial
      neural network [RMSE (%)=12.03, 12.15, 11.74, 10.7] and the multiple linear
      regression model [RMSE (%)=10.62, 10.68, 10.62, 10.54] were not able to reduce
      their forecast error over the same horizons to the same extent. For this
      particular application the nonlinear auto-regressive model with exogenous input
      can be presented as a more accurate alternative to conventional regression
      modeling techniques, especially for short-term milk-yield predictions.

PMID- 24731635
TI  - Preventive effect of fermented Maillard reaction products from milk proteins in
      cardiovascular health.
AB  - The aim of this study was to determine the dual effect of Maillard reaction and
      fermentation on the preventive cardiovascular effects of milk proteins. Maillard
      reaction products (MRP) were prepared from the reaction between milk proteins,
      such as whey protein concentrates (WPC) and sodium caseinate (SC), and lactose.
      The hydrolysates of MRP were obtained from fermentation by lactic acid bacteria
      (LAB; i.e., Lactobacillus gasseri H10, L. gasseri H11, Lactobacillus fermentum
      H4, and L. fermentum H9, where human-isolated strains were designated H1 to H15),
      which had excellent proteolytic and 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical
      scavenging activities (>20%). The antioxidant activity of MRP was greater than
      that of intact proteins in assays of the reaction with 2,2'-azino-bis (3
      ethylbenzothiazoline-6-sulfonic acid) diammonium salt and trivalent ferric ions;
      moreover, the effect of MRP was synergistically improved by fermentation. The
      Maillard reaction dramatically increased the level of antithrombotic activity and
      3-hydroxy-3-methylglutaryl-CoA reductase (HMGR) inhibitory effect of milk
      proteins, but did not change the level of activity for micellar cholesterol
      solubility. Furthermore, specific biological properties were enhanced by
      fermentation. Lactobacillus gasseri H11 demonstrated the greatest activity for
      thrombin and HMGR inhibition in Maillard-reacted WPC, by 42 and 33%,
      respectively, whereas hydrolysates of Maillard-reacted SC fermented by L.
      fermentum H9 demonstrated the highest reduction rate for micellar cholesterol
      solubility, at 52%. In addition, the small compounds that were likely released by
      fermentation of MRP were identified by size-exclusion chromatography. Therefore,
      MRP and hydrolysates of fermented MRP could be used to reduce cardiovascular
      risks. 

PMID- 24731636
TI  - Effects of ethyl-3-nitrooxy propionate and 3-nitrooxypropanol on ruminal
      fermentation, microbial abundance, and methane emissions in sheep.
AB  - The aim of this work was to investigate the effect of feeding ethyl-3-nitrooxy
      propionate (E3NP) and 3-nitrooxypropanol (3 NP), 2 recently developed compounds
      with potential antimethanogenic activity, in vitro and in vivo in nonlactating
      sheep on ruminal methane production, fermentation pattern, the abundance of major
      microbial groups, and feed degradability. Three experiments were conducted, 1 in
      vitro and 2 in vivo. The in vitro batch culture trial (experiment 1) tested 2
      doses of E3NP and 3 NP (40 and 80 MUL/L), which showed a substantial reduction of
      methane production (up to 95%) without affecting concentration of volatile fatty
      acids (VFA). The 2 in vivo trials were conducted over 16 d (experiment 2) and 30
      d (experiment 3) to study their effects in sheep. In experiment 2, 6 adult
      nonpregnant sheep, with permanent rumen cannula and fed alfalfa hay and oats
      (60:40), were treated with E3NP at 2 doses (50 and 500 mg/animal per day). After
      7, 14, and 15 d of treatment, methane emissions were recorded in respiration
      chambers and rumen fluid samples were collected for VFA analysis and
      quantification of bacterial, protozoal, and archaeal numbers by real-time PCR.
      Methane production decreased by 29% compared with the control with the higher
      dose of E3NP on d 14 to 15. A decrease in the acetate:propionate ratio was
      observed without detrimental effects on dry matter intake. In experiment 3, 9
      adult nonpregnant sheep, with permanent rumen cannula and fed with alfalfa hay
      and oats (60:40), were treated with E3NP or 3 NP at one dose (100mg/animal per
      day) over 30 d. On d 14 and d 29 to 30, methane emissions were recorded in
      respiration chambers. Rumen fluid samples were collected on d 29 and 30 for VFA
      analysis and quantification of bacterial, protozoal, and archaeal numbers by real
      time PCR. In addition, on d 22 and 23, samples of oats and alfalfa hay were
      incubated in the rumen of sheep to determine dry matter ruminal degradation over
      24 and 48 h, respectively; no effect was observed (78.6, 78.3, and 78.8% of
      alfalfa and 74.2, 74.0, and 70.6% of oats in control, E3NP, and 3 NP groups,
      respectively). A reduction in methane production was observed for both additives
      at d 14 and d 29 to 30. In both treatments, the acetate:propionate ratio was
      significantly decreased. Likewise, total concentrations of the analyzed microbial
      groups in the rumen showed no difference among treatments and doses for both
      experiments. Both tested compounds showed promise as methane inhibitors in the
      rumen, with no detrimental effects on fermentation or intake, which would need to
      be confirmed in lactating animals.

PMID- 24731637
TI  - A field study of the behavioral and physiological effects of varying amounts of
      shade for lactating cows at pasture.
AB  - Shade reduces the negative effects of heat load, but little is known about how
      much is required for efficient cooling in commercial settings. The effect of the
      amount of shade on 8 Holstein-Friesian herds was studied for 2 consecutive
      summers (mean temperature: 23  degrees C) on 6 commercial, pasture-based dairy
      farms. Farms varied in the amount of natural shade provided (range: 0 to 15.6m(2)
      shade/cow). Time spent in shade, near water, eating, ruminating, lying, and
      standing were recorded between 1000 and 1530 h in 31 shaded and 11 unshaded
      paddocks using 20-min instantaneous scan observations of 15 focal cows/herd.
      Respiration rate and panting score (0 to 4.5) was recorded for focal animals once
      per hour. The total numbers of cows in shade, near water, and with panting scores
      >= 2 were recorded every 30 min. Cows without shade spent 4% more time lying than
      cows with shade (standard error of the difference, SED = 1.9%). A larger
      proportion of the herd had panting scores >= 2 when no shade was available (6 vs.
      2% of the herd, SED = 1.2%), and respiration rates were higher by 8 breaths/min
      in cows without shade (SED = 4.7 breaths/min). Under the conditions tested, the
      maximum proportion of the herd that was observed using the shade increased by
      3.1% for every 1-m(2) increase in shade size [standard error (SE) = 1.51%], and
      all cows were first seen simultaneously using shade when 2m(2)/cow was provided.
      For every 1-m(2) increase in shade, 0.3% fewer cows had panting score >= 2 (SE =
      0.12%). We observed no significant relationships between the amount of shade
      available and any other variables. Although additional work is required to make
      specific recommendations, these results indicate that providing more shade
      allowed a higher proportion of animals to use this resource and reduced
      respiratory signs of heat load.

PMID- 24731638
TI  - Association between polyunsaturated fatty acid-derived oxylipid biosynthesis and
      leukocyte inflammatory marker expression in periparturient dairy cows.
AB  - Peripheral blood mononuclear leukocytes from periparturient cows can have
      exacerbated inflammatory responses that contribute to disease incidence and
      severity. Oxylipids derived from the oxygenation of polyunsaturated fatty acids
      (PUFA) can regulate the magnitude and duration of inflammation. Although PUFA
      substrate for oxylipid biosynthesis in leukocytes is known to change across the
      periparturient period, the plasma oxylipid profile and how this profile relates
      to leukocyte inflammatory phenotype is not clear. The objective of this study was
      to determine if a relationship exists between the profile of pro- and
      antiinflammatory plasma oxylipids and the inflammatory phenotype of peripheral
      blood leukocytes during the periparturient period. Seven multiparous Holsteins
      were sampled from the prepartum period through peak lactation. Plasma oxylipids
      were measured by liquid chromatography-mass spectrometry, peripheral leukocyte
      mRNA expression was measured by quantitative PCR, and PUFA content of peripheral
      blood mononuclear cells was measured by gas chromatography-mass spectrometry.
      Concentrations of several hydroxyl products of linoleic and arachidonic acid
      changed over time. Linoleic acid and arachidonic acid concentrations in
      leukocytes increased during early lactation, suggesting that substrate
      availability for hydroxyoctadecadienoic and hydroxyeicosatetraenoic acid
      biosynthesis may influence the oxylipid profile. Leukocyte mRNA expressions of IL
      12B, IL-1B, inducible nitric oxide synthase 2, and cyclooxygenase 2 were
      correlated with several plasma oxylipids. These are the first observations
      linking leukocyte inflammatory gene responses to shifts in oxylipid biosynthesis
      in periparturient dairy cows. 

PMID- 24731639
TI  - Rheological and structural properties of differently acidified and renneted milk
      gels.
AB  - In this study we assessed the rheological and structural properties of
      differently acidified and renneted milk gels by controlling pH value and
      renneting extent. Skim milk were exactly renneted to 4 extents (20, 35, 55, and
      74%) and then direct acidified to the desired pH (4.8, 5.0, 5.2, 5.5, 5.8, and
      6.2), respectively. Rheological properties were assessed by dynamic rheological
      measurements, structural properties were studied by spontaneous whey separation
      and confocal laser scanning micrograph, and protein interactions were studied by
      dissociation test. Results showed that minimally renneted milk samples (20 and
      35%) formed weak gels with low storage modulus, and the acidification range
      within which gels could form was narrow (pH <= 5.2). Highly renneted milk samples
      formed more gels with high storage modulus. The results of this study revealed
      that acidification determined the structural properties of highly renneted milk
      gels. As pH increased from 5.0 to 6.2, highly renneted milk gels had lower loss
      tangent, decreased spontaneous syneresis, and smaller pores. For both the low and
      high rennetings, divalent calcium bonds contributed less at low pH than at high
      pH. In conclusion, renneting increased the pH range suitable for gel formation;
      acidification determined the spontaneous syneresis and microstructure of highly
      renneted milk gels.

PMID- 24731640
TI  - Effects of supplemental chromium propionate and rumen-protected amino acids on
      nutrient metabolism, neutrophil activation, and adipocyte size in dairy cows
      during peak lactation.
AB  - The objective of this study was to evaluate effects of chromium propionate
      (CrPr), rumen-protected lysine and methionine (RPLM), or both on metabolism,
      neutrophil function, and adipocyte size in lactating dairy cows (38 +/- 15 d in
      milk). Forty-eight individually fed Holstein cows (21 primiparous, 27
      multiparous) were stratified by calving date in 12 blocks and randomly assigned
      to 1 of 4 treatments within block. Treatments were control, CrPr (8 mg/d of Cr,
      KemTRACE brand chromium propionate 0.04%, Kemin Industries Inc., Des Moines, IA),
      RPLM (10 g/d lysine and 5 g/d methionine intestinally available, from LysiPEARL
      and MetiPEARL, Kemin Industries Inc.), or CrPr plus RPLM. Treatments were fed for
      35 d; blood plasma samples were collected ond 21 and 35 of treatment, and blood
      neutrophils were isolated from 24 cows for analysis of tumor necrosis factor
      alpha (TNFalpha) and interleukin 1beta (IL-1beta) transcript abundance in the
      basal state and after 12h of lipopolysaccharide (LPS) activation. Tailhead
      subcutaneous adipose tissue samples were collected ond 35 for measurement of
      adipocyte size. Plasma glucose, nonesterified fatty acids, and glucagon
      concentrations were unaffected by treatments, whereas plasma insulin
      concentration was increased by RPLM. Basal TNFalpha transcript abundance in
      neutrophils was not affected by treatment, but basal IL-1beta transcript
      abundance was decreased by RPLM and tended to be increased by CrPr. After LPS
      activation, CrPr increased neutrophil TNFalpha transcript abundance. In addition,
      RPLM*parity interactions were detected for both TNFalpha and IL-1beta abundance
      after LPS activation, reflecting enhanced responses in primiparous cows and
      attenuated responses in multiparous cows supplemented with RPLM. Adipocyte size
      was not affected by treatment. Supplemental CrPr and RPLM had minimal effects on
      metabolism when fed for 35 d near peak lactation but may modulate innate immune
      function in lactating dairy cows.

PMID- 24731641
TI  - Effects of supplemental chromium propionate and rumen-protected amino acids on
      productivity, diet digestibility, and energy balance of peak-lactation dairy
      cattle.
AB  - Chromium (Cr) feeding in early lactation increased milk production in some
      studies, but responses to dietary Cr during peak lactation have not been
      evaluated. Furthermore, interactions of essential amino acids (AA) and Cr have
      not been explored. Our objective was to evaluate responses to CrPr (KemTRACE
      chromium propionate 0.04%, Kemin Industries Inc., Des Moines, IA) and rumen
      protected Lys (LysiPEARL, Kemin Industries Inc.) and Met (MetiPEARL, Kemin
      Industries Inc.) and their interaction in peak-lactation cows. Forty-eight
      individually fed Holstein cows (21 primiparous, 27 multiparous, 38 +/- 15 d in
      milk) were stratified by calving date in 12 blocks and randomly assigned to 1 of
      4 treatments within block. Treatments were control, CrPr (8 mg/d of Cr), RPLM (10
      g/d of Lys and 5 g/d of Met, intestinally available), or CrPr plus RPLM.
      Treatments were premixed with ground corn and top-dressed at 200 g/d for 35 d.
      Diets consisted of corn silage, alfalfa hay, and concentrates, providing
      approximately 17% crude protein, 31% neutral detergent fiber, and 40% nonfiber
      carbohydrates. Dry matter intake (DMI) significantly increased with the inclusion
      of CrPr (22.2 vs. 20.8 +/- 0.67 kg/d), and energy-corrected milk (ECM) yield
      tended to increase. In addition, CrPr increased milk protein yield and tended to
      increase DMI in primiparous cows but not in multiparous cows. A CrPr*week
      interaction was detected for milk lactose content, which was increased by CrPr
      during wk 1 only (4.99 vs. 4.88 +/- 0.036%). As a proportion of plasma AA, lysine
      increased and methionine tended to increase in response to RPLM, but the
      inclusion of RPLM decreased N efficiency (milk protein N:N intake). Digestible
      energy intake, gross energy digestibility, and energy balance were not affected
      by treatments. We observed no treatment effects on feed efficiency or changes in
      body weight or body condition score. In summary, feeding CrPr increased DMI and
      tended to increase ECM in cows fed for 5 wk near peak lactation, with primiparous
      cows showing greater responses in DMI and milk protein yield than multiparous
      cows.

PMID- 24731642
TI  - Effect of 2 herbal intramammary products on milk quantity and quality compared
      with conventional and no dry cow therapy.
AB  - Dry cow therapy, administered at the end of lactation, is aimed at eliminating
      current and preventing future intramammary (IMM) bacterial infections and
      typically involves intramammary administration of antibiotics. Certified organic
      dairies in the United States are restricted from using antibiotics and must
      consider an alternative therapy or no dry cow therapy. The current study compared
      2 herbal products to conventional dry cow therapy and no treatment for a total of
      5 treatments over 2 trials. Trial 1 was conducted over 3 yr on 1 research farm
      and trial 2 included 4 commercial farms plus the research herd over 2 yr.
      Treatments included (1) a conventional IMM antibiotic and internal teat sealant
      (penicillin-dihydrostreptomycin and bismuth subnitrate; CON); (2) an herbal IMM
      product purported to act as a teat sealant (Cinnatube, New AgriTech Enterprises,
      Locke, NY; CIN); (3) an herbal IMM product (Phyto-Mast, Bovinity Health LLC,
      Narvon, PA; P-M); (4) Phyto-Mast and Cinnatube (PC); or (5) no dry cow therapy
      (NT). Each treatment group was balanced by breed, lactation number, due date,
      herd, and year. However, the CON treatment was used only in the research herd
      because of the intent to avoid antibiotic usage on the other 4 farms. Comparisons
      among treatments included the difference between pre- and posttreatment 305-d
      mature equivalent milk production (trial 1), somatic cell score change from dry
      off to freshening at the cow and quarter levels (trials 1 and 2), and milk
      microbiology change over the dry period (trial 2). We detected no significant
      differences among treatments for milk yield differences between the lactation
      following treatment and the lactation preceding treatment. Changes in somatic
      cell score from one lactation to the next also did not differ significantly among
      treatments in either trial. Cure rates were not significantly different among
      treatments; only 19.6% of all quarters were infected at dry off. The proportion
      of quarters with new infections at 3 to 5d postcalving did not significantly
      differ among treatments, except between CIN and NT. Percentages (least squares
      means +/- standard error) of quarters with new infections were 24 +/- 21% for
      CON, 15 +/- 7% for CIN, 30 +/- 10% for P-M, 32 +/- 11% for PC, and 35 +/- 11% for
      NT. The efficacy of the herbal products was similar to that of conventional
      therapy, and the herbal products had no apparent adverse effects.

PMID- 24731643
TI  - Evaluation of the Minnesota Easy Culture System II Bi-Plate and Tri-Plate for
      identification of common mastitis pathogens in milk.
AB  - The objective of this study was to validate use of the Minnesota Easy Culture
      System II Bi-Plate and Tri-Plate (University of Minnesota Laboratory for Udder
      Health, St. Paul) to identify common mastitis pathogens in milk. A total of 283
      quarter and composite milk samples submitted to the University of Minnesota
      Laboratory for Udder Health during the spring of 2010 were cultured
      simultaneously using 3 methods: standard laboratory culture (reference method)
      and the Minnesota Easy Culture System II Bi-Plate and Tri-Plate methods. Bi-Plate
      and Tri-Plate cultures were incubated for 18 to 24h and interpreted by 2
      independent, untrained readers within 5h of each other. An experienced technician
      completed the standard laboratory culture. For each sample, all 3 study personnel
      recorded the culture result (yes/no) for each of the following diagnostic
      categories: no bacterial growth (NG), mixed (2 organisms), contaminated (3 or
      more organisms), gram-positive (GP), gram-negative (GN), Staphylococcus spp.,
      Streptococcus spp., Streptococcus agalactiae, Streptococcus dysgalactiae,
      Streptococcus uberis, Enterococcus spp., Staphylococcus aureus, coagulase
      negative staphylococci, Escherichia coli, Klebsiella spp., and other. For each
      category, the prevalence, sensitivity, specificity, accuracy, and predictive
      values of a positive and negative test were calculated, and the agreement between
      readers and between each reader and the laboratory was assessed. Specificity,
      overall accuracy, and negative predictive values were generally high (>80%) for
      the Bi-Plate and Tri-Plate for each category. Sensitivity and positive predictive
      values were intermediate (>60%) or high (>80%) for the broad categories of NG,
      GP, GN, Staphylococcus spp. and Streptococcus spp., and for Staph. aureus, but
      were generally lower (<60%) for other more specific categories. Similarly,
      interreader agreement (kappa value) was moderate to substantial (40-80%) for the
      broad categories of NG, GP, GN, Staphylococcus spp. and Streptococcus spp., and
      for Staph. aureus and E. coli, but was lower for other categories. The Tri-Plate
      had a higher sensitivity, accuracy, and negative predictive value for
      Streptococcus spp., and higher interreader agreement for some of the more
      specific categories. Our conclusion was that Bi-Plate and Tri-Plate results will
      be most reliable when used to classify infections in broad diagnostic categories
      such NG, GP, or GN. The Bi-Plate and Tri-Plate will have intermediate ability to
      identify infections as being caused by Staphylococcus spp., Streptococcus spp.,
      or Staph. aureus. 

PMID- 24731644
TI  - Short communication: investigation of aflatoxin M1 levels in infant follow-on
      milks and infant formulas sold in the markets of Ankara, Turkey.
AB  - Aflatoxins are fungal toxins known to be carcinogenic and are classified as food
      contaminants. This study was performed to investigate aflatoxin (AF) M1 levels in
      baby foods sold in Ankara (Turkey) and to evaluate the obtained results according
      to the Turkish Food Codex (TFC). For this purpose, a total of 84 baby food
      samples (50 follow-on milks and 34 infant formulas) were obtained from different
      markets in Ankara and the presence of AFM1 in the samples was analyzed by ELISA.
      In 32 (38.1%) of 84 infant food samples, the presence of AFM1 was detected in
      concentrations ranging between 0.0055 and 0.0201 ug/kg. The mean level (+/-
      standard error) of AFM1 was found to be 0.0089 +/- 0.0006 ug/kg in positive
      infant follow-on milks. Aflatoxin M1 was detected in only 1 infant formula sample
      (2.94%) at a concentration of 0.0061 ug/kg. The extrapolated levels of AFB1
      contamination in feedstuffs were calculated based on levels of AFM1 in baby food
      samples. The data estimating AFB1 contamination in dairy cattle feedstuff
      indicate that contamination may range from 0.3410 to 1.2580 ug/kg, with the mean
      level (+/- standard error) being 0.5499 +/- 0.0385 ug/kg, which is lower than the
      level set by the TFC and European Union regulations (5 ug/kg). According to the
      obtained results, the levels of AFM1 in analyzed samples were within the allowed
      limit (0.025 ug/kg) set in the TFC. Low levels of AFM1 in infant follow-on milks
      and infant formula samples obtained during the study do not pose a health risk to
      infants.

PMID- 24731645
TI  - Effect of a high-palmitic acid fat supplement on milk production and apparent
      total-tract digestibility in high- and low-milk yield dairy cows.
AB  - The effect of a high-palmitic acid fat supplement was tested in 12 high-producing
      (mean = 42.1 kg/d) and 12 low-producing (mean = 28.9 kg/d) cows arranged in a
      replicated 3 * 3 Latin square design. Experimental periods were 21 d, with 18d of
      diet adaptation and 3 d of sample collection. Treatments were (1) control (no
      supplemental fat), (2) high-palmitic acid (PA) supplement (84% C16:0), and (3) Ca
      salts of palm fatty acid (FA) supplement (Ca-FA). The PA supplement had no effect
      on milk production, but decreased dry matter intake by 7 and 9% relative to the
      control in high- and low-producing cows, respectively, and increased feed
      efficiency by 8.5% in high-producing cows compared with the control. Milk fat
      concentration and yield were not affected by PA relative to the control in high-
      or low-producing cows, although PA increased the yield of milk 16-C FA by more
      than 85 g/d relative to the control. The Ca-FA decreased milk fat concentration
      compared with PA in high-, but not in low-producing cows. In agreement, Ca-FA
      dramatically increased milk fat concentration of trans-10 C18:1 and trans-10, cis
      12 conjugated linoleic acid (>300%) compared with PA in high-producing cows, but
      not in low-producing cows. No effect of treatment on milk protein concentration
      or yield was detected. The PA supplement also increased 16-C FA apparent
      digestibility by over 10% and increased total FA digestibility compared with the
      control in high- and low-producing cows. During short-term feeding, palmitic acid
      supplementation did not increase milk or milk fat yield; however, it was
      efficiently absorbed, increased feed efficiency, and increased milk 16-C FA
      yield, while minimizing alterations in ruminal biohydrogenation commonly observed
      for other unsaturated fat supplements. Longer-term experiments will be necessary
      to determine the effects on energy balance and changes in body reserves.

PMID- 24731647
TI  - Short communication: Prediction of intake in dairy cows under tropical
      conditions.
AB  - A meta-analysis was conducted to develop a model for predicting dry matter intake
      (DMI) in dairy cows under the tropical conditions of Brazil and to assess its
      adequacy compared with 5 currently available DMI prediction models: Agricultural
      and Food Research Council (AFRC); National Research Council (NRC); Cornell Net
      Carbohydrate and Protein System (CNCPS; version 6); and 2 other Brazilian models.
      The data set was created using 457 observations (n=1,655 cows) from 100 studies,
      and it was randomly divided into 2 subsets for statistical analysis. The first
      subset was used to develop a DMI prediction equation (60 studies; 309 treatment
      means) and the second subset was used to assess the adequacy of DMI predictive
      models (40 studies; 148 treatment means). The DMI prediction model proposed in
      the current study was developed using a nonlinear mixed model analysis after
      reparameterizing the NRC equation but including study as a random effect in the
      model. Body weight (mean = 540 +/- 57.6 kg), 4% fat-corrected milk (mean = 21.3
      +/- 7.7 kg/d), and days in milk (mean = 110 +/- 62 d) were used as independent
      variables in the model. The adequacy of the DMI prediction models was evaluated
      based on coefficient of determination, mean square prediction error (MSPE), root
      MSPE (RMSPE), and concordance correlation coefficient (CCC). The observed DMI
      obtained from the data set used to evaluate the prediction models averaged 17.6
      +/- 3.2 kg/d. The following model was proposed: DMI (kg/d) = [0.4762 (+/- 0.0358)
      * 4% fat-corrected milk + 0.07219 (+/- 0.00605) * body weight(0.75)] * (1 - e(
      0.03202 (+/- 0.00615) * [days in milk + 24.9576 (+/- 5.909)])). This model
      explained 93.0% of the variation in DMI, predicting it with the lowest mean bias
      (0.11 kg/d) and RMSPE (4.9% of the observed DMI) and the highest precision
      [correlation coefficient estimate (rho) = 0.97] and accuracy [bias correction
      factor (Cb)=0.99]. The NRC model prediction equation explained 92.0% of the
      variation in DMI and had the second lowest mean bias (0.42 kg/d) and RMSPE (5.8%
      of the observed DMI), as well as the second highest precision (rho = 0.94) and
      accuracy (Cb = 0.98). The CNCPS and AFRC DMI prediction models explained 93.0 and
      85.0% of the variation in DMI but underpredicted DMI by 1.8 and 1.4 kg/d,
      respectively. These 2 models (CNCPS and AFRC) resulted, respectively, in RMSPE of
      11.3 and 10.7% of the observed DMI, with moderate to high precision (rho = 0.81
      and 0.82) and accuracy (Cb = 0.84 and 0.89). The remaining 2 models resulted in
      the poorest results, underpredicting DMI by 2.3 and 1.9 kg/d, with RMSPE of 22.8
      and 14.9% of the observed DMI and moderate to low precision (rho = 0.49 and 0.76)
      and accuracy (Cb = 0.81 and 0.86). The new model derived from the current meta
      analytical approach provided the best accuracy and precision for predicting DMI
      in lactating dairy cows under Brazilian conditions.

PMID- 24731646
TI  - Relationships between fertility and postpartum changes in body condition and body
      weight in lactating dairy cows.
AB  - The relationship between energy status and fertility in dairy cattle was
      retrospectively analyzed by comparing fertility with body condition score (BCS)
      near artificial insemination (AI; experiment 1), early postpartum changes in BCS
      (experiment 2), and postpartum changes in body weight (BW; experiment 3). To
      reduce the effect of cyclicity status, all cows were synchronized with Double
      Ovsynch protocol before timed AI. In experiment 1, BCS of lactating dairy cows (n
      = 1,103) was evaluated near AI. Most cows (93%) were cycling at initiation of the
      breeding Ovsynch protocol (first GnRH injection). A lower percentage pregnant to
      AI (P/AI) was found in cows with lower (<= 2.50) versus higher (>= 2.75) BCS
      (40.4 vs. 49.2%). In experiment 2, lactating dairy cows on 2 commercial dairies
      (n = 1,887) were divided by BCS change from calving until the third week
      postpartum. Overall, P/AI at 70-d pregnancy diagnosis differed dramatically by
      BCS change and was least for cows that lost BCS, intermediate for cows that
      maintained BCS, and greatest for cows that gained BCS [22.8% (180/789), 36.0%
      (243/675), and 78.3% (331/423), respectively]. Surprisingly, a difference existed
      between farms with BCS change dramatically affecting P/AI on one farm and no
      effect on the other farm. In experiment 3, lactating dairy cows (n = 71) had BW
      measured weekly from the first to ninth week postpartum and then had
      superovulation induced using a modified Double-Ovsynch protocol. Cows were
      divided into quartiles (Q) by percentage of BW change (Q1 = least change; Q4 =
      most change) from calving until the third week postpartum. No effect was detected
      of quartile on number of ovulations, total embryos collected, or percentage of
      oocytes that were fertilized; however, the percentage of fertilized oocytes that
      were transferable embryos was greater for cows in Q1, Q2, and Q3 than Q4 (83.8,
      75.2, 82.6, and 53.2%, respectively). In addition, percentage of degenerated
      embryos was least for cows in Q1, Q2, and Q3 and greatest for Q4 (9.6, 14.5,
      12.6, and 35.2% respectively). In conclusion, for cows synchronized with a Double
      Ovsynch protocol, an effect of low BCS (<= 2.50) near AI on fertility was
      detected, but change in BCS during the first 3 wk postpartum had a more profound
      effect on P/AI to first timed AI. This effect could be partially explained by the
      reduction in embryo quality and increase in degenerate embryos byd 7 after AI in
      cows that lost more BW from the first to third week postpartum.

PMID- 24731648
TI  - Parent-adolescent interaction and risk of adolescent internet addiction: a
      population-based study in Shanghai.
AB  - BACKGROUND: Family-based intervention is essential for adolescents with
      behavioral problems. However, limited data are available on the relationship
      between family-based factors and adolescent internet addiction (AIA). We aimed to
      examine this relationship using a representative sample of Shanghai adolescents.
      METHODS: In October 2007, a total of 5122 adolescents were investigated from 16
      high schools via stratified-random sampling in Shanghai. Self-reported and
      anonymous questionnaires were used to assess parent-adolescent interaction and
      family environments. AIA was assessed by DRM-52 Scale, developed from Young's
      Internet-addiction Scale, using seven subscales to evaluate psychological
      symptoms of AIA. RESULTS: Adjusting for adolescents' ages, genders, socio
      economic status, school performances and levels of the consumption expenditure,
      strong parental disapproval of internet-use was associated with AIA (vs. parental
      approval, OR = 2.20, 95% CI: 1.24-3.91). Worse mother-adolescent relationships
      were more significantly associated with AIA (OR = 3.79, 95% CI: 2.22-6.48) than
      worse father-adolescent relationships (OR = 1.76, 95% CI: 1.10-2.80). Marital
      status of "married-but-separated" and family structure of "left-behind
      adolescents" were associated with symptoms of some subscales. When having high
      monthly allowance, resident students tended to develop AIA but commuter students
      did not. Family social-economic status was not associated with the development of
      AIA. CONCLUSIONS: The quality of parent-adolescent relationship/communication was
      closely associated with the development of AIA, and maternal factors were more
      significantly associated with development of AIA than paternal factors. Family
      social-economic status moderated adolescent internet-use levels but not the
      development of AIA.

PMID- 24731649
TI  - Development of tartaric esters as bifunctional additives of methanol-gasoline.
AB  - BACKGROUND: Methanol has become an alternative fuel for gasoline, which is facing
      a rapidly rising world demand with a limited oil supply. Methanol-gasoline has
      been used in China, but phase stability and vapor lock still need to be resolved
      in methanol-gasoline applications. In this paper, a series of tartaric esters
      were synthesized and used as phase stabilizers and saturation vapor pressure
      depressors for methanol-gasoline. RESULTS: The results showed that the phase
      stabilities of tartaric esters for methanol-gasoline depend on the length of the
      alkoxy group. Several tartaric esters were found to be effective in various
      gasoline-methanol blends, and the tartaric esters display high capacity to
      depress the saturation vapor pressure of methanol-gasoline. CONCLUSION: According
      to the results, it can be concluded that the tartaric esters have great potential
      to be bifunctional gasoline-methanol additives.

PMID- 24731650
TI  - Effect of resveratrol on blood pressure: a meta-analysis of randomized controlled
      trials.
AB  - BACKGROUND & AIMS: The results of human clinical trials that have investigated
      the effects of resveratrol on blood pressure are inconsistent. We aimed to
      quantitatively evaluate the effects of resveratrol on systolic blood pressure
      (SBP) and diastolic blood pressure (DBP). METHODS: We conducted a strategic
      literature search of PubMed, EMBASE, MEDLINE, and the Cochrane Library (updated
      to January, 2014) for randomized controlled trials that evaluate the effects of
      resveratrol on SBP and DBP. Study quality was assessed using the Jadad scale.
      Weighted mean differences were calculated for net changes in SBP and DBP using
      fixed-effects or random-effects models. We performed pre-specified subgroup,
      sensitivity and meta-regression analyses to evaluate potential the heterogeneity.
      Dose effects of resveratrol on SBP and DBP were estimated using meta-regression
      analyses. RESULTS: Six studies comprising a total of 247 subjects were included
      in our meta-analysis. The overall outcome of the meta-analysis indicates that
      resveratrol consumption can not significantly reduce SBP and DBP. Subgroup
      analyses indicated that higher-dose of resveratrol consumption (>= 150 mg/d)
      significantly reduces SBP of -11.90 mmHg (95% CI: -20.99, -2.81 mmHg, P = 0.01),
      whereas lower dose of resveratrol did not show a significant lowering effect on
      SBP. The meta-regression analyses did not indicate dose effects of resveratrol on
      SBP or DBP. CONCLUSIONS: The present meta-analysis indicates that resveratrol
      consumption significantly decreases the SBP level at the higher dose, while
      resveratrol has no significant effects on DBP levels. Additional high-quality
      studies are needed to further evaluate the causal conclusions.

PMID- 24731651
TI  - Impact of accuracy of fractional flow reserve to reduction of microvascular
      resistance after intracoronary adenosine in patients with angina pectoris or non
      ST-segment elevation myocardial infarction.
AB  - Our study aimed to elucidate mechanisms underlying discordance between fractional
      flow reserve (FFR) and hyperemic stenosis resistance (hSR) in some patient
      subsets. To do this, we enrolled 30 consecutive patients with stable angina or
      non-ST elevation myocardial infarction (non-STEMI) and with a nonculprit
      intermediate coronary lesion (40% to 70%) by coronary angiography. We measured
      aortic pressure, flow velocity, and pressure distal to lesion simultaneously at
      basal level and during adenosine-induced (fixed intracoronary dose of 120 MUg)
      hyperemia using a dual-sensor-equipped guidewire. Microvascular resistance (MR;
      pressure distal to lesion/flow velocity, mm Hg/cm/s) and variation (Delta) in MR
      levels were calculated both at baseline and after hyperemia, whereas FFR (cutoff
      <0.80) and hSR [(aortic pressure - pressure distal to lesion)/flow velocity,
      cutoff >0.80 mm Hg/cm/s] were assessed after intracoronary adenosine. Twenty
      three patients (76.7%) showed concordance and 7 patients (23.3%) showed
      discordance between FFR and hSR (all cases with FFR >0.80 and hSR >0.80).
      Discordant patients presented more frequently with non-STEMI (85.7% vs 39.1%, p =
      0.04), significantly higher C-reactive protein serum levels (median
      [interquartile range] 5.9 [5.1 to 6.8] vs 4.9 [3.7 to 6.2] mg/L, p = 0.007), and
      lower DeltaMR (p = 0.03) values compared with concordant patients. In conclusion,
      patients with non-STEMI and those with increased C-reactive protein levels show a
      lower reduction in MR after intracoronary adenosine-induced hyperemia, leading to
      FFR underestimation. 

PMID- 24731652
TI  - Cardiac sarcoidosis detected by late gadolinium enhancement and prevalence of
      atrial arrhythmias.
AB  - Cardiovascular magnetic resonance (CMR) imaging is being increasingly used to
      help identify patients with cardiac sarcoidosis (CS). Whereas ventricular
      arrhythmias have been well studied in this population, atrial arrhythmias have
      not been thoroughly investigated. We sought to better characterize the arrhythmia
      burden of a cohort of patients diagnosed with CS by CMR imaging. Patients with
      biopsy-proven extracardiac sarcoidosis were referred to the University of Chicago
      for evaluation of the presence of CS. CMR imaging was used to categorize the
      patients into 2 groups; those with and those without late gadolinium enhancement
      (LGE) for comparison of arrhythmic events. Arrhythmic evaluation included Holter
      monitor, event recorder, electrophysiology testing, or implantable cardioverter
      defibrillator (ICD) interrogation; 192 consecutive patients were evaluated with
      CMR imaging, 57 of whom did not have ambulatory monitoring results and thus were
      excluded. LGE was present in 44 patients. Atrial arrhythmias were documented in
      16 patients (36%) with myocardial LGE and in 11 patients (12%) without myocardial
      LGE (p = 0.002). Ventricular arrhythmias were documented in 27% of patients with
      myocardial LGE and 2.2% of LGE-negative patients (p = 0.00076). Of 26 LGE
      positive patients with ICDs, 8 (30.8%) received therapies, 3 (11.5%) of which
      were inappropriate for atrial arrhythmias. In conclusion, atrial arrhythmias were
      documented more frequently than ventricular arrhythmias in patients with
      sarcoidosis with cardiac involvement and were 3 times more prevalent than in
      patients with sarcoidosis without cardiac involvement. Risk-benefit assessment of
      anticoagulation for primary prevention of stroke should be performed for patients
      with CS. In patients receiving implantable defibrillators, programming to
      minimize inappropriate ICD shocks for atrial arrhythmias must be considered.

PMID- 24731653
TI  - Clinical implications of T-wave inversion in an asymptomatic population
      undergoing annual medical screening (from the Korean Air Forces Electrocardiogram
      Screening).
AB  - This study aimed to determine prevalence, differentiate underlying causes, and
      identify the benign group in subjects with asymptomatic T-wave inversion (TWI).
      We retrospectively read 12-lead electrocardiograms from 3,929 consecutive
      asymptomatic men in the air force (3,929 participants, mean age 39.3 +/- 8.7
      years) who underwent medical screening at the Aerospace Medical Center, Korea,
      from September 2010 to August 2012. TWIs other than in right precordial leads (V1
      and V2) were present in 23 men (0.6%). All subjects with persistent TWI for 1
      year (n = 18) underwent additional study, with the exception of 1 patient who
      refused further evaluation. Of 17 subjects with investigated persistent TWI, 8
      (47.1%) had an apically displaced papillary muscle, 5 (29.4%) exhibited
      idiopathic TWI, 3 (17.6%) had apical hypertrophic cardiomyopathy, and 1 (5.9%)
      had Maron type 2 hypertrophic cardiomyopathy with dynamic left ventricular
      outflow obstruction. The depth of TWI was significantly shallow in the benign
      group (idiopathic TWI, 1.6 +/- 0.5 mm) compared with potentially nonbenign group
      (the others; 5.5 +/- 3.3 mm, p = 0.021). Lateral lead TWI was significantly
      correlated with potentially nonbenign group (46% vs 0%, p = 0.049). In
      conclusion, asymptomatic TWI is not rare (0.6%), even in a healthy population
      such as Korean Air Force society, and at least 29.4% of subjects with TWI are
      considered to belong to the benign group that does not require aggressive
      evaluation and criteria of TWI <=2 mm other than lateral leads without co
      morbidity could help to distinguish the benign group from the potentially
      nonbenign group. 

PMID- 24731655
TI  - Seasonal and regional variation in Takotsubo cardiomyopathy.

PMID- 24731654
TI  - A systematic review and collaborative meta-analysis to determine the incremental
      value of copeptin for rapid rule-out of acute myocardial infarction.
AB  - Multiple studies have evaluated copeptin, a surrogate for arginine vasopressin,
      in the diagnosis of acute myocardial infarction (AMI) with mixed results. A
      systematic review and collaborative meta-analysis were performed for diagnosis of
      AMI and assessment of prognosis in patients presenting to the emergency
      department with chest pain. MEDLINE/PubMed, Cochrane CENTRAL, and EMBASE were
      searched for studies assessing copeptin in such patients. Study investigators
      were contacted, and many provided previously unpublished data. Random-effects
      methods were used to compare the data for copeptin, troponin, and their
      combination. There were a total of 9,244 patients from the 14 included studies.
      Mean age was 62 years; 64% were men; and 18.4% were ultimately diagnosed with
      AMI. Patients with AMI had a higher presentation copeptin level than those
      without AMI (22.8 vs 8.3 pmol/L, respectively, p <0.001). Although troponin had
      better diagnostic accuracy than copeptin for AMI, the combination of copeptin and
      troponin significantly improved the sensitivity (0.905 [0.888 to 0.921] vs 0.686
      [0.661 to 0.710], respectively, p <0.001) and negative predictive value (0.97
      [0.964 to 0.975] vs 0.93 [0.924 to 0.936], respectively, p <0.001) compared with
      troponin alone. Elevation in copeptin carried a similar risk of all-cause
      mortality to an elevation in troponin (odds ratio 5.84 vs 6.74, respectively, p =
      0.67). In conclusion, copeptin not only identifies patients at risk of all-cause
      mortality, but its addition to troponin improved the sensitivity and negative
      likelihood ratio for diagnosis of AMI compared with troponin alone. Thus,
      copeptin may help identify patients who may be safely discharged early from the
      emergency department. 

PMID- 24731656
TI  - Effects of iron overload on chronic metabolic diseases.
AB  - Iron can affect the clinical course of several chronic metabolic diseases such as
      type 2 diabetes, obesity, non-alcoholic fatty liver disease, and atherosclerosis.
      Iron overload can affect major tissues involved in glucose and lipid metabolism
      (pancreatic beta cells, liver, muscle, and adipose tissue) and organs affected by
      chronic diabetic complications. Because iron is a potent pro-oxidant, fine-tuned
      control mechanisms have evolved to regulate entry, recycling, and loss of body
      iron. These mechanisms include the interplay of iron with transferrin, ferritin,
      insulin, and hepcidin, as well as with adipokines and proinflammatory molecules.
      An imbalance of these homoeostatic mechanisms results in systemic and parenchymal
      siderosis that contributes to organ damage (such as beta-cell dysfunction,
      fibrosis in liver diseases, and atherosclerotic plaque growth and instability).
      Conversely, iron depletion can exert beneficial effects in patients with iron
      overload and even in healthy frequent blood donors. Regular assessment of iron
      balance should be recommended for patients with chronic metabolic diseases, and
      further research is needed to produce guidelines for the identification of
      patients who would benefit from iron depletion. 

PMID- 24731658
TI  - Would you fly with a pilot on insulin?

PMID- 24731657
TI  - The polygenic nature of hypertriglyceridaemia: implications for definition,
      diagnosis, and management.
AB  - Plasma triglyceride concentration is a biomarker for circulating triglyceride
      rich lipoproteins and their metabolic remnants. Common mild-to-moderate
      hypertriglyceridaemia is typically multigenic, and results from the cumulative
      burden of common and rare variants in more than 30 genes, as quantified by
      genetic risk scores. Rare autosomal recessive monogenic hypertriglyceridaemia can
      result from large-effect mutations in six different genes. Hypertriglyceridaemia
      is exacerbated by non-genetic factors. On the basis of recent genetic data, we
      redefine the disorder into two states: severe (triglyceride concentration >10
      mmol/L), which is more likely to have a monogenic cause; and mild-to-moderate
      (triglyceride concentration 2-10 mmol/L). Because of clustering of susceptibility
      alleles and secondary factors in families, biochemical screening and counselling
      for family members is essential, but routine genetic testing is not warranted.
      Treatment includes management of lifestyle and secondary factors, and
      pharmacotherapy. In severe hypertriglyceridaemia, intervention is indicated
      because of pancreatitis risk; in mild-to-moderate hypertriglyceridaemia,
      intervention can be indicated to prevent cardiovascular disease, dependent on
      triglyceride concentration, concomitant lipoprotein disturbances, and overall
      cardiovascular risk. 

PMID- 24731659
TI  - Adipokines in gestational diabetes.
AB  - Gestational diabetes is characterised by glucose intolerance with onset or first
      recognition during pregnancy. The disease shows facets of the metabolic syndrome
      including obesity, insulin resistance, and dyslipidaemia. Adipokines are a group
      of proteins secreted from adipocytes, which are dysregulated in obesity and
      contribute to metabolic and vascular complications. Recent studies have assessed
      the role of various adipokines including leptin, adiponectin, tumour necrosis
      factor alpha (TNFalpha), adipocyte fatty acid-binding protein (AFABP), retinol
      binding protein 4 (RBP4), resistin, NAMPT, SERPINA12, chemerin, progranulin, FGF
      21, TIMP1, LCN2, AZGP1, apelin (APLN), and omentin in gestational diabetes. This
      Review provides an overview of these key adipokines, their regulation in, and
      potential contribution to gestational diabetes. Based on the evidence so far, the
      adipokines adiponectin, leptin, TNFalpha, and AFABP seem to be the most probable
      candidates involved in the pathophysiology of gestational diabetes. 

PMID- 24731661
TI  - Surgery for diabetes in low and middle-income countries.

PMID- 24731662
TI  - Definition of intervention points in prediabetes.
AB  - With respect to clinical phenotype and pathophysiology, prediabetes is akin to
      diabetes. Prediabetes is prevalent in the global population, and those affected
      are at high risk of progression to overt diabetes, and also at risk of
      cardiovascular disease (CVD). Progression to diabetes can occur because of
      worsening insulin resistance, beta-cell dysfunction, or both, but the timecourse
      can be non-linear and, therefore, unpredictable. Intervention-by lifestyle
      modification, glucose-lowering drugs, or a combination-can postpone deterioration
      of glucose control, but effects of intervention are variable and can be
      transient. Furthermore, to what extent interventions can reduce cardiovascular
      risk is uncertain. Lifestyle intervention mainly hinges on weight loss; as such,
      risk of failure in the long-term is high, and implementation at the community
      level is difficult. The ideal candidate for intervention is an individual with
      prediabetes-identified by targeted screening-with many well documented
      cardiovascular risk factors, and who is highly motivated to initiate and maintain
      multifactorial risk-control using a personalised mix of lifestyle-adaptation and
      pharmacological treatment. 

PMID- 24731660
TI  - Age-related and disease-related muscle loss: the effect of diabetes, obesity, and
      other diseases.
AB  - The term sarcopenia refers to the loss of muscle mass that occurs with ageing. On
      the basis of study results showing that muscle mass is only moderately related to
      functional outcomes, international working groups have proposed that loss of
      muscle strength or physical function should also be included in the definition.
      Irrespective of how sarcopenia is defined, both low muscle mass and poor muscle
      strength are clearly highly prevalent and important risk factors for disability
      and potentially mortality in individuals as they age. Many chronic diseases, in
      addition to ageing, could also accelerate decrease of muscle mass and strength,
      and this effect could be a main underlying mechanism by which chronic diseases
      cause physical disability. In this Review, we address both age-related and
      disease-related muscle loss, with a focus on diabetes and obesity but including
      other disease states, and potential common mechanisms and treatments. Development
      of treatments for age-related and disease-related muscle loss might improve
      active life expectancy in older people, and lead to substantial health-care
      savings and improved quality of life. 

PMID- 24731663
TI  - Skeletal health in adults with HIV infection.
AB  - Concern has been raised that HIV infection, its treatment, or both adversely
      affect skeletal health. Cross-sectional studies show that bone mineral density
      (BMD) is 3-5% lower in patients infected with HIV than in uninfected controls,
      but patients with HIV infection are, on average, 5 kg lighter than uninfected
      people. After this weight difference is accounted for, BMD differences are
      smaller and not clinically relevant. Longitudinal studies show short-term BMD
      loss of 2-4% over 1-2 years when antiretroviral therapy is started, followed by
      longer periods of BMD increase or stability. Losses are greatest with treatment
      regimens that contain tenofovir. Patients infected with HIV have slightly higher
      fracture rates than controls, but the increased risk of fracture is substantially
      attenuated by adjustment for traditional risk factors for fracture. These
      reassuring findings suggest that management of skeletal health in HIV should
      follow guidelines for the general population. In general, effective
      antiretroviral treatment and avoidance of undernutrition are the two most
      important factors for maintenance of skeletal health in patients infected with
      HIV.

PMID- 24731665
TI  - The importance of dynamic signalling for endocrine regulation and drug
      development: relevance for glucocorticoid hormones.
AB  - Glucocorticoid hormones are heavily prescribed for several indications, including
      hormone replacement, anti-inflammatory effects, and antineoplastic effects. The
      pharmaceutical industry has put much effort into the development of novel potent
      glucocorticoid agonists, whereas there has been little enthusiasm for development
      of temporal aspects of glucocorticoid drugs. Glucocorticoids are normally
      secreted in a highly dynamic fashion, not only in the well known 24 h circadian
      rhythm, but also in an approximately hourly ultradian rhythm. These rhythms are
      crucial for normal gene regulation and for optimum cognitive function. In this
      Personal View, we discuss how understanding normal oscillatory patterns of
      glucocorticoid secretion could help investigators to develop novel glucocorticoid
      therapeutics that maximise the beneficial effect and diminish unwanted side
      effects. 

PMID- 24731664
TI  - Endocrine consequences of anorexia nervosa.
AB  - Anorexia nervosa is prevalent in adolescents and young adults, and endocrine
      changes include hypothalamic amenorrhoea; a nutritionally acquired growth-hormone
      resistance leading to low concentrations of insulin-like growth factor-1 (IGF-1);
      relative hypercortisolaemia; decreases in leptin, insulin, amylin, and incretins;
      and increases in ghrelin, peptide YY, and adiponectin. These changes in turn have
      harmful effects on bone and might affect neurocognition, anxiety, depression, and
      the psychopathology of anorexia nervosa. Low bone-mineral density (BMD) is
      particularly concerning, because it is associated with changes in bone
      microarchitecture, strength, and clinical fractures. Recovery leads to
      improvements in many--but not all--hormonal changes, and deficits in bone accrual
      can persist. Oestrogen-replacement therapy, primarily via the transdermal route,
      increases BMD in adolescents, although catch-up is incomplete. In adults, oral
      oestrogen--combined with recombinant human IGF-1 in one study and bisphosphonates
      in another--increased BMD, but not to the normal range. More studies are
      necessary to investigate the optimum therapeutic approach in patients with, or
      recovering from, anorexia nervosa.

PMID- 24731666
TI  - Combating the dual burden: therapeutic targeting of common pathways in obesity
      and type 2 diabetes.
AB  - The increasing prevalence of obesity is contributing substantially to the ongoing
      epidemic of type 2 diabetes. Abdominal adiposity, a feature of ectopic fat
      syndrome, is associated with silent inflammation, abnormal hormone secretion, and
      various metabolic disturbances that contribute to insulin resistance and insulin
      secretory defects, resulting in type 2 diabetes, and induce a toxic pattern that
      leads to cardiovascular disease, liver pathologies, and cancer. Despite the
      importance of weight control strategies in the prevention and management of type
      2 diabetes, long-term results from lifestyle or drug interventions are generally
      disappointing. Furthermore, most of the classic glucose-lowering drugs have a
      side-effect of weight gain, which renders the management of most overweight or
      obese people with type 2 diabetes even more challenging. Many anti-obesity
      pharmacological drugs targeting central control of appetite were withdrawn from
      the market because of safety concerns. The gastrointestinal lipase inhibitor
      orlistat was the only anti-obesity drug available until the recent US, but not
      European, launch of phentermine-controlled-release topiramate and lorcaserin.
      Improved knowledge about bodyweight regulation opens new prospects for the
      potential use of peptides derived from the gut or the adipose tissue. Combination
      therapy will probably be necessary to avoid compensatory mechanisms and
      potentiate initial weight loss while avoiding weight regain. New glucose-lowering
      treatments, especially glucagon-like peptide-1 receptor agonists and sodium
      glucose cotransporter-2 inhibitors, offer advantages over traditional
      antidiabetic drugs by promoting weight loss while improving glucose control. In
      this Review, we explore the overlapping pathophysiology and also how various
      treatments can, alone or in combination, combat the dual burden of obesity and
      type 2 diabetes. 

PMID- 24731667
TI  - The bone-fat interface: basic and clinical implications of marrow adiposity.
AB  - Obesity and osteoporosis are two of the most common chronic disorders of the 21st
      century. Both are accompanied by significant morbidity. The only place in the
      mammalian organism where bone and fat lie adjacent to each other is in the bone
      marrow. Marrow adipose tissue is a dynamic depot that probably exists as both
      constitutive and regulated compartments. Adipocytes secrete cytokines and
      adipokines that either stimulate or inhibit adjacent osteoblasts. The
      relationship of marrow adipose tissue to other fat depots is complex and might
      play very distinct parts in modulation of metabolic homoeostasis, haemopoiesis,
      and osteogenesis. Understanding of the relationship between bone and fat cells
      that arise from the same progenitor within the bone marrow niche provides insight
      into the pathophysiology of age-related osteoporosis, diabetes, and obesity. 

PMID- 24731668
TI  - Heart failure: a cardiovascular outcome in diabetes that can no longer be
      ignored.
AB  - In patients with type 1 or type 2 diabetes, glycaemic exposure assessed as HbA1c
      correlates strongly with risk of future microvascular and macrovascular
      complications. Improved glucose control substantially reduces the risk of
      microvascular complications and, with extended follow-up, modestly reduces the
      risk of atherosclerotic events. The lowering of HbA1c concentrations by newly
      developed glucose-lowering drugs (alone or when added to other glucose-lowering
      drugs) has been used, until recently, as a surrogate measure of their potential
      to lower cardiovascular risk. This assumption is no longer acceptable, and now
      demonstration of cardiovascular safety has been mandated by regulatory
      authorities. A major concern, however, is the universal absence in any large
      scale trials of new glucose-lowering drugs of hospital admission for heart
      failure as a prespecified component of the primary composite cardiovascular
      outcomes. This omission is important because hospital admission for heart failure
      is a common and prognostically important cardiovascular complication of diabetes.
      Moreover, it is the one cardiovascular outcome for which the risk has been shown
      unequivocally to be increased by some glucose-lowering therapies. As such, we
      believe that heart failure should be systematically evaluated in cardiovascular
      outcome trials of all new glucose-lowering drugs. 

PMID- 24731669
TI  - Non-alcoholic fatty liver disease as a cause and a consequence of metabolic
      syndrome.
AB  - Metabolic syndrome is a cluster of metabolic abnormalities that identifies people
      at risk of diabetes and cardiovascular disease, whereas non-alcoholic fatty liver
      disease (NAFLD) is defined as a disorder with excess fat in the liver due to non
      alcoholic causes. Two key components of metabolic syndrome, glucose and
      triglycerides, are overproduced by the fatty liver. The liver is therefore a key
      determinant of metabolic abnormalities. The prevalence of both metabolic syndrome
      and NAFLD increases with obesity. Other acquired causes for both disorders
      include excessive intake of simple sugars and physical inactivity. Both disorders
      predict type 2 diabetes, cardiovascular disease, non-alcoholic steatohepatitis
      (NASH), and hepatocellular carcinoma. Because metabolic syndrome can be defined
      in many different ways, NAFLD might be a more direct predictor of these diseases.
      Half of people with NAFLD carry at least one variant (G) allele at rs738409 in
      the PNPLA3 gene, which is associated with high liver fat content. Steatosis in
      PNPLA3-associated NAFLD is not accompanied by features of metabolic syndrome. All
      forms of NAFLD increase the risk of NASH, cirrhosis, and hepatocellular
      carcinoma. 

PMID- 24731670
TI  - Metabolic syndrome: a sympathetic disease?
AB  - Metabolic syndrome is associated with adverse health outcomes and is a growing
      problem worldwide. Although efforts to harmonise the definition of metabolic
      syndrome have helped to better understand the prevalence and the adverse outcomes
      associated with the disorder on a global scale, the mechanisms underpinning the
      metabolic changes that define it are incompletely understood. Accumulating
      evidence from laboratory and human studies suggests that activation of the
      sympathetic nervous system has an important role in metabolic syndrome. Indeed,
      treatment strategies commonly recommended for patients with metabolic syndrome,
      such as diet and exercise to induce weight loss, are associated with sympathetic
      inhibition. Pharmacological and device-based approaches to target activation of
      the sympathetic nervous system directly are available and have provided evidence
      to support the important part played by sympathetic regulation, particularly for
      blood pressure and glucose control. Preliminary evidence is encouraging, but
      whether therapeutically targeting sympathetic overactivity could help to prevent
      metabolic syndrome and attenuate its adverse outcomes remains to be determined. 

PMID- 24731671
TI  - Eprotirome in patients with familial hypercholesterolaemia (the AKKA trial): a
      randomised, double-blind, placebo-controlled phase 3 study.
AB  - BACKGROUND: Eprotirome is a liver-selective thyroid hormone receptor agonist that
      has been shown to lower plasma LDL cholesterol concentrations in previous phase 1
      and 2 studies of patients with dyslipidaemia. We aimed to assess the long-term
      safety and efficacy of 50 MUg and 100 MUg eprotirome in patients with familial
      hypercholesterolaemia. METHODS: For this randomised, double-blind, placebo
      controlled, parallel-group, phase 3 clinical trial, we enrolled patients between
      Oct 3, 2011, and Feb 14, 2012, at 53 sites in 11 countries in Europe, Africa, and
      south Asia. Patients were eligible for enrolment if they were aged 18 years or
      older, diagnosed with heterozygous familial hypercholesterolaemia, and had not
      reached target LDL cholesterol concentrations after at least 8 weeks of statin
      therapy with or without ezetimibe. We used a computer-generated randomisation
      sequence to allocate patients to one of three groups: 50 MUg eprotirome, 100 MUg
      eprotirome, or placebo. This trial was planned for 52-76 weeks, with primary
      efficacy analysis at 12 weeks, but it was prematurely terminated when another
      study found that eprotirome causes cartilage damage in dogs. Although it was
      impossible to meet the predefined study outcomes, we analysed changes in the
      concentrations of LDL cholesterol and other lipids, liver parameters, thyroid
      hormone concentrations, and adverse effects of treatment with eprotirome versus
      placebo at 6 weeks of treatment. Analysis was done in all patients who received 6
      weeks of treatment. This study is registered with ClinicalTrials.gov, number
      NCT01410383. FINDINGS: We enrolled 236 patients, randomly allocating 80 to
      receive placebo, 79 to receive 50 MUg eprotirome, and 77 to receive 100 MUg
      eprotirome. 69 patients reached the 6 week timepoint (23 given placebo, 24 given
      50 MUg eprotirome, and 22 given 100 MUg eprotirome). Mean LDL cholesterol
      concentrations increased by 9% (95% CI -2 to 20) in the placebo group, decreased
      by 12% (-28 to 4%; p=0.0677 vs placebo) in the 50 MUg eprotirome group, and
      decreased by 22% (-32 to -13%; p=0.0045 vs placebo) in the 100 MUg eprotirome
      group. We noted statistically significant increases between both eprotirome
      groups and placebo in aspartate aminotransferase (AST; p<0.0001), alanine
      aminotransferase (ALT; p<0.0001), conjugated bilirubin (p=0.0006), and gamma
      glutamyltranspeptidase (p<0.0001). Four patients had to discontinue or interrupt
      study treatment before trial termination due to AST increases between the upper
      limit of normal (ULN) and six times ULN, and ALT concentrations between three and
      seven times ULN. Although we detected no changes in serum concentrations of
      thyroid-stimulating hormone or free tri-iodothyronine, free tetra-iodothyronine
      decreased by 19% (23 to 16) in the 50 MUg eprotirome group and 27% (30 to 23) in
      the 100 MUg eprotirome group (p<0.0001 vs placebo for both groups).
      INTERPRETATION: Our findings show that eprotirome can lower LDL cholesterol
      concentrations in patients with familial hypercholesterolaemia when added to
      conventional statin treatment with or without ezetimibe, but that it has the
      potential to induce liver injury. These findings, along with findings of
      cartilage damage in dogs, raise serious doubts about selective thyroid hormone
      mimetics as a therapeutic approach to lower LDL cholesterol concentrations.
      FUNDING: Karo Bio AB.

PMID- 24731672
TI  - Exenatide once weekly versus insulin glargine for type 2 diabetes (DURATION-3): 3
      year results of an open-label randomised trial.
AB  - BACKGROUND: When patients with type 2 diabetes start their first injectable
      therapy, clinicians can choose between glucagon-like peptide-1 (GLP-1) receptor
      agonists and basal insulins. In DURATION-3, exenatide once weekly was compared
      with insulin glargine (henceforth, glargine) as first injectable therapy. Here,
      we report the results of the final 3-year follow-up. METHODS: DURATION-3 was an
      open-label randomised trial done between May 13, 2008, and Jan 30, 2012. Patients
      with type 2 diabetes aged 18 years or older were enrolled at 72 sites worldwide.
      They were eligible when they had suboptimum glycaemic control (HbA1c 7.1-11.0%
      [54-97 mmol/mol]) despite maximum tolerated doses of metformin alone or with a
      sulfonylurea for at least 3 months, a stable bodyweight for at least 3 months,
      and a BMI of 25-45 kg/m(2) (23-45 kg/m(2) in South Korea and Taiwan). Patients
      were randomly assigned (1:1) by computer-generated random sequence with an
      interactive voice-response system (block size four, stratified by country and
      concomitant therapy) to once-weekly exenatide (2 mg subcutaneous injection) or
      once-daily glargine (titrated to target) to be given in addition to their
      existing oral glucose-lowering regimens. The primary efficacy measure at 3 years
      was change in HbA1c from baseline in patients given at least one dose of the
      assigned drug (ie, analyses by modified intention to treat). Patients,
      investigators, and data analysts were not masked to treatment assignment. This
      trial is registered with ClinicalTrials.gov, number NCT00641056. FINDINGS: 456
      patients underwent randomisation and received at least one dose of the assigned
      drug (233 given exenatide, 223 glargine). At 3 years, least-squares mean HbA1c
      change was -1.01% (SE 0.07) in the exenatide group versus -0.81% (0.07) in the
      glargine group (least-squares mean difference -0.20%, SE 0.10, 95% CI -0.39 to 
      0.02; p=0.03). Transient gastrointestinal adverse events characteristic of GLP-1
      receptor agonists were more frequent with exenatide than glargine (nausea: 36
      [15%] of 233 patients vs five [2%] of 223; vomiting: 15 [6%] vs six [3%];
      diarrhoea: 32 [14%] vs 15 [7%]), although frequency of these events did decrease
      after week 26 in the exenatide group. The proportion of patients who reported
      serious adverse events in the exenatide group (36 patients [15%]) was the same as
      that in the glargine group (33 [15%]). The exposure-adjusted rate of overall
      hypoglycaemia was three times higher in patients given glargine (0.9 events per
      patient per year) than in those given exenatide (0.3 events per patient per
      year). INTERPRETATION: Efficacy of once-weekly exenatide is sustained for 3
      years. GLP-1 receptor agonists could be a viable long-term injectable treatment
      option in patients with type 2 diabetes who have not yet started taking insulin.
      FUNDING: Amylin Pharmaceuticals and Eli Lilly.

PMID- 24731675
TI  - Inducing thyrotoxicosis in the liver to treat raised cholesterol.

PMID- 24731673
TI  - Heritability of variation in glycaemic response to metformin: a genome-wide
      complex trait analysis.
AB  - BACKGROUND: Metformin is a first-line oral agent used in the treatment of type 2
      diabetes, but glycaemic response to this drug is highly variable. Understanding
      the genetic contribution to metformin response might increase the possibility of
      personalising metformin treatment. We aimed to establish the heritability of
      glycaemic response to metformin using the genome-wide complex trait analysis
      (GCTA) method. METHODS: In this GCTA study, we obtained data about HbA1c
      concentrations before and during metformin treatment from patients in the
      Genetics of Diabetes Audit and Research in Tayside Scotland (GoDARTS) study,
      which includes a cohort of patients with type 2 diabetes and is linked to
      comprehensive clinical databases and genome-wide association study data. We
      applied the GCTA method to estimate heritability for four definitions of
      glycaemic response to metformin: absolute reduction in HbA1c; proportional
      reduction in HbA1c; adjusted reduction in HbA1c; and whether or not the target on
      treatment HbA1c of less than 7% (53 mmol/mol) was achieved, with adjustment for
      baseline HbA1c and known clinical covariates. Chromosome-wise heritability
      estimation was used to obtain further information about the genetic architecture.
      FINDINGS: 5386 individuals were included in the final dataset, of whom 2085 had
      enough clinical data to define glycaemic response to metformin. The heritability
      of glycaemic response to metformin varied by response phenotype, with a
      heritability of 34% (95% CI 1-68; p=0.022) for the absolute reduction in HbA1c,
      adjusted for pretreatment HbA1c. Chromosome-wise heritability estimates suggest
      that the genetic contribution is probably from individual variants scattered
      across the genome, which each have a small to moderate effect, rather than from a
      few loci that each have a large effect. INTERPRETATION: Glycaemic response to
      metformin is heritable, thus glycaemic response to metformin is, in part,
      intrinsic to individual biological variation. Further genetic analysis might
      enable us to make better predictions for stratified medicine and to unravel new
      mechanisms of metformin action. FUNDING: Wellcome Trust.

PMID- 24731674
TI  - Cardiovascular mortality, all-cause mortality, and diabetes incidence after
      lifestyle intervention for people with impaired glucose tolerance in the Da Qing
      Diabetes Prevention Study: a 23-year follow-up study.
AB  - BACKGROUND: Lifestyle interventions among people with impaired glucose tolerance
      reduce the incidence of diabetes, but their effect on all-cause and
      cardiovascular disease mortality is unclear. We assessed the long-term effect of
      lifestyle intervention on long-term outcomes among adults with impaired glucose
      tolerance who participated in the Da Qing Diabetes Prevention Study. METHODS: The
      study was a cluster randomised trial in which 33 clinics in Da Qing, China
      serving 577 adults with impaired glucose tolerance-were randomised (1:1:1:1) to a
      control group or lifestyle intervention groups (diet or exercise or both).
      Patients were enrolled in 1986 and the intervention phase lasted for 6 years. In
      2009, we followed up participants to assess the primary outcomes of
      cardiovascular mortality, all-cause mortality, and incidence of diabetes in the
      intention-to-treat population. FINDINGS: Of the 577 patients, 439 were assigned
      to the intervention group and 138 were assigned to the control group (one refused
      baseline examination). 542 (94%) of 576 participants had complete data for
      mortality and 568 (99%) contributed data to the analysis. 174 participants died
      during the 23 years of follow-up (121 in the intervention group vs 53 in the
      control group). Cumulative incidence of cardiovascular disease mortality was
      11.9% (95% CI 8.8-15.0) in the intervention group versus 19.6% (12.9-26.3) in the
      control group (hazard ratio [HR] 0.59, 95% CI 0.36-0.96; p=0.033). All-cause
      mortality was 28.1% (95% CI 23.9-32.4) versus 38.4% (30.3-46.5; HR 0.71, 95% CI
      0.51-0.99; p=0.049). Incidence of diabetes was 72.6% (68.4-76.8) versus 89.9%
      (84.9-94.9; HR 0.55, 95% CI 0.40-0.76; p=0.001). INTERPRETATION: A 6-year
      lifestyle intervention programme for Chinese people with impaired glucose
      tolerance can reduce incidence of cardiovascular and all-cause mortality and
      diabetes. These findings emphasise the long-term clinical benefits of lifestyle
      intervention for patients with impaired glucose tolerance and provide further
      justification for adoption of lifestyle interventions as public health measures
      to control the consequences of diabetes. FUNDING: Centers for Disease Control and
      Prevention, WHO, the China-Japan Friendship Hospital, Da Qing First Hospital.

PMID- 24731677
TI  - Personalising metformin therapy: a clinician's perspective.

PMID- 24731676
TI  - Basal insulin or longacting GLP-1 receptor agonists-making the right choice.

PMID- 24731678
TI  - Fruit juice: just another sugary drink?

PMID- 24731679
TI  - Bariatric surgery for diabetes control in overweight people.

PMID- 24731680
TI  - The long-term benefits of lifestyle interventions for prevention of diabetes.

PMID- 24731681
TI  - Acute hyperammonemic encephalopathy in a non-cirrhotic patient with
      hepatocellular carcinoma reversed by arginine therapy.

PMID- 24731682
TI  - Ictal topography of epileptic genital pain: a case presentation with SPECT
      subtraction analysis.

PMID- 24731683
TI  - State of the art review in gonadal dysgenesis: challenges in diagnosis and
      management.
AB  - Gonadal dysgenesis, a condition in which gonadal development is interrupted
      leading to gonadal dysfunction, is a unique subset of disorders of sexual
      development (DSD) that encompasses a wide spectrum of phenotypes ranging from
      normally virilized males to slightly undervirilized males, ambiguous phenotype,
      and normal phenotypic females. It presents specific challenges in diagnostic work
      up and management. In XY gonadal dysgenesis, the presence of a Y chromosome or Y
      chromosome material renders the patient at increased risk for developing gonadal
      malignancy. No universally accepted guidelines exist for identifying the risk of
      developing a malignancy or for determining either the timing or necessity of
      performing a gonadectomy in patients with XY gonadal dysgenesis. Our goal was to
      evaluate the literature and develop evidence-based medicine guidelines with
      respect to the diagnostic work-up and management of patients with XY gonadal
      dysgenesis. We reviewed the published literature and used the Grading of
      Recommendation, Assessment, Development, and Evaluation (GRADE) system when
      appropriate to grade the evidence and to provide recommendations for the
      diagnostic work-up, malignancy risk stratification, timing or necessity of
      gonadectomy, role of gonadal biopsy, and ethical considerations for performing a
      gonadectomy. Individualized health care is needed for patients with XY gonadal
      dysgenesis, and the decisions regarding gonadectomy should be tailored to each
      patient based on the underlying diagnosis and risk of malignancy. Our
      recommendations, based on the evidence available, add an important component to
      the diagnostic and management armament of physicians who treat patients with
      these conditions. 

PMID- 24731684
TI  - Dielectric analysis of depth dependent curing behavior of dental resin
      composites.
AB  - OBJECTIVES: The aim of this study is to investigate depth dependent changes of
      polymerization process and kinetics of visible light-curing (VLC) dental
      composites in real-time. The measured quantity - "ion viscosity" determined by
      dielectric analysis (DEA) - provides the depth dependent reaction rate which is
      correlated to the light intensity available in the corresponding depths derived
      from light transmission measurements. METHODS: The ion viscosity curves of two
      composites (VOCO Arabesk Top and Grandio) were determined during irradiation of
      40s with a light-curing unit (LCU) in specimen depths of
      0.5/0.75/1.0/1.25/1.5/1.75 and 2.0mm using a dielectric cure analyzer (NETZSCH
      DEA 231 with Mini IDEX sensors). The thickness dependent light transmission was
      measured by irradiation composite specimens of various thicknesses on top of a
      radiometer setup. RESULTS: The shape of the ion viscosity curves depends strongly
      on the specimen thickness above the sensor. All curves exhibit a range of linear
      time dependency of the ion viscosity after a certain initiation time. The
      determined initiation times, the slopes of the linear part of the curves, and the
      ion viscosities at the end of the irradiation differ significantly with depth
      within the specimen. The slopes of the ion viscosity curves as well as the light
      intensity values decrease with depth and fit to the Lambert-Beer law. The
      corresponding attenuation coefficients are determined for Arabesk Top OA2 to
      1.39mm(-1) and 1.48mm(-1), respectively, and for Grandio OA2 with 1.17 and
      1.39mm(-1), respectively. For thicknesses exceeding 1.5mm a change in
      polymerization behavior is observed as the ion viscosity increases subsequent to
      the linear range indicating some kind of reaction acceleration. SIGNIFICANCE: The
      two VLC composites and different specimen thicknesses discriminate significantly
      in their ion viscosity evolution allowing for a precise characterization of the
      curing process even with respect to the polymerization mechanism.

PMID- 24731685
TI  - On the expressiveness, validity and reproducibility of models of language
      evolution: Comment on "Modelling language evolution: Examples and predictions" by
      Tao Gong, Shuai Lan, and Menghan Zhang.

PMID- 24731686
TI  - Current trends in bioelectrics for reversible cell membrane manipulation: Comment
      on "Physical methods for genetic transformation of fungi and yeast" by Rivera et
      al.

PMID- 24731687
TI  - When the boundaries between physics and biology blur: A promising future for
      fungi as producers of valuable recombinant proteins: Reply to comments on:
      "Physical methods for genetic transformation of fungi and yeast".

PMID- 24731688
TI  - Comparative evaluation of alcoholic handrub: science or marketing?

PMID- 24731689
TI  - A cost-utility analysis of drug treatments in patients with HBeAg-positive
      chronic hepatitis B in Thailand.
AB  - BACKGROUND: Only lamivudine has been included for patients with chronic hepatitis
      B (CHB) in the National List of Essential Drugs (NLED), a pharmaceutical
      reimbursement list in Thailand. There have also been no economic evaluation
      studies of CHB drug treatments conducted in Thailand yet. In order to fill this
      gap in policy research, the objective of this study was to compare the cost
      utility of each drug therapy (Figure 1) with palliative care in patients with
      HBeAg-positive CHB. METHODS: A cost-utility analysis using an economic evaluation
      model was performed to compare each drug treatment for HBeAg-positive CHB
      patients. A Markov model was used to estimate the relevant costs and health
      outcomes during a lifetime horizon based on a societal perspective. Direct
      medical costs, direct non-medical costs, and indirect costs were included, and
      health outcomes were denoted in life years (LYs) and quality-adjusted life years
      (QALYs). The results were presented as an incremental cost effectiveness ratio
      (ICER) in Thai baht (THB) per LY or QALY gained. One-way sensitivity and
      probabilistic sensitivity analyses were applied to investigate the effects of
      model parameter uncertainties. RESULTS: The ICER values of providing generic
      lamivudine with the addition of tenofovir when drug resistance occurred, generic
      lamivudine with the addition of tenofovir based on the road map guideline, and
      tenofovir monotherapy were -14,000 (USD -467), -8,000 (USD -267) , and -5,000
      (USD -167) THB per QALY gained, respectively. However, when taking into account
      all parameter uncertainties in the model, providing generic lamivudine with the
      addition of tenofovir when drug resistance occurred (78% and 75%) and tenofovir
      monotherapy (18% and 24%) would yield higher probabilities of being cost
      effective at the societal willingness to pay thresholds of 100,000 (USD 3,333)
      and 300,000 (USD 10,000) THB per QALY gained in Thailand, respectively.
      CONCLUSIONS: Based on the policy recommendations from this study, the Thai
      government decided to include tenofovir into the NLED in addition to generic
      lamivudine which is already on the list. Moreover, the results have shown that
      the preferred treatment regimen involves using generic lamivudine as the first
      line drug with tenofovir added if drug resistance occurs in HBeAg-positive CHB
      patients.

PMID- 24731690
TI  - Bioprocessing of Stichococcus bacillaris strain siva2011.
AB  - BACKGROUND: Globally, the development of a cost-effective long-term renewable
      energy infrastructure is one of the most challenging problems faced by society
      today. Microalgae are rich in potential biofuel substrates such as lipids,
      including triacylglycerols (TAGs). Some of these algae also biosynthesize small
      molecule hydrocarbons. These hydrocarbons can often be used as liquid fuels,
      often with more versatility and by a more direct approach than some TAGs.
      However, the appropriate TAGs, accumulated from microalgae biomass, can be used
      as substrates for different kinds of renewable liquid fuels such as biodiesel and
      jet fuel. RESULTS: This article describes the isolation and identification of a
      lipid-rich, hydrocarbon-producing alga, Stichococcus bacillaris strain siva2011,
      together with its bioprocessing, hydrocarbon and fatty acid methyl ester (FAME)
      profiles. The S. bacillaris strain siva2011 was scaled-up in an 8 L bioreactor
      with 0.2% CO2. The C16:0, C16:3, C18:1, C18:2 and C18:3 were 112.2, 9.4, 51.3,
      74.1 and 69.2 mg/g dry weight (DW), respectively. This new strain produced a
      significant amount of biomass of 3.79 g/L DW on day 6 in the 8 L bioreactor and
      also produced three hydrocarbons. CONCLUSIONS: A new oil-rich microalga S.
      bacillaris strain siva2011 was discovered and its biomass has been scaled-up in a
      newly designed balloon-type bioreactor. The TAGs and hydrocarbons produced by
      this organism could be used as substrates for jet fuel or biodiesel.

PMID- 24731691
TI  - Outcome of delayed primary internal fixation of distal radius fractures: a
      comparative study.
AB  - INTRODUCTION AND AIM: Operative fixation of distal radius fractures using fixed
      angle devices has become increasingly common. Although good to excellent results
      have been reported in acute fractures, little is currently known regarding the
      fixation of healing displaced distal radius fractures that were presented late.
      The aim of this study was to evaluate the results of internal fixation of distal
      radius fractures presented late (>21 days) as compared with an acute-care control
      group. METHODS: Forty patients operated on for displaced distal radius fractures,
      presenting more than 21 days after injury (delayed treatment (DT) group), were
      compared with 75 age-matched controls with acute fracture repair (<=21 days). The
      same surgical approach was used in both groups, together with dorsal soft-tissue
      and brachioradialis release. No osteotomy was required. Direct and indirect
      reduction aids were used. A fixed-angle device (DVR; Biomet Inc., Warsaw, IN,
      USA) was used in both groups. Mean follow-up was 3.4 years. Quick DASH
      (Disabilities of the Arm, Shoulder and Hand) and Short Form 12 scores were used
      to evaluate outcome, as well as radiographic analysis for Arbeitsgemeinschaft fur
      Osteosynthesefragen(AO)/Orthopaedic Trauma Association(OTA) classification, volar
      tilt, radial inclination and radial length. RESULTS: Average age was 53 years in
      both groups and male to female (M/F) ratio was similar in the study groups. Mean
      time to surgery was 30 days in the DT group and 8 days in the control group.
      There were significantly more type C (91.5% vs. 67.5%) fractures in the control
      group. The average quick DASH score was 27.1 in the DT group as compared with 6.3
      in the control group (p<0.03); however, when controlling for two outlier cases
      with complications (hardware irritation and a sensory neuropathy) there was no
      significant difference. Volar tilt, radial inclination and length were similar in
      both groups and were within normal anatomical values. CONCLUSIONS: Delayed
      primary operative fixation of displaced unstable distal radial fractures is a
      viable option for cases that were presented late, with predictable, favourable
      results. Neither extensile approaches nor formal osteotomies are required.

PMID- 24731692
TI  - Hook leverage technique for reduction of intertrochanteric fracture.

PMID- 24731693
TI  - Radiographic assessment of hand dressings in children.

PMID- 24731694
TI  - The impact of magnetic resonance spectroscopy in elucidating the role of
      apolipoprotein E epsilon4 in preclinical Alzheimer's disease.

PMID- 24731695
TI  - KIBRA, aging, and gene by environmental interaction: an effect to remember?

PMID- 24731696
TI  - The thorny problem of dyskinesias: dendritic spines, synaptic plasticity, and
      striatal dysfunction.

PMID- 24731697
TI  - Heterogeneity in periodontitis prevalence in the Hispanic Community Health
      Study/Study of Latinos.
AB  - PURPOSE: The aim of the study was to examine acculturation and established risk
      factors in explaining variation in periodontitis prevalence among Hispanic/Latino
      subgroups. METHODS: Participants were 12,730 dentate adults aged 18-74 years
      recruited into the Hispanic Community Health Study/Study of Latinos (HCHS/SOL)
      from four U.S. field centers between 2008 and 2011. A standardized periodontal
      assessment measured probing pocket depth and gingival recession at six sites per
      tooth for up to 28 teeth. Periodontitis was defined according to the Centers for
      Disease Control and Prevention and American Academy of Periodontology case
      classifications developed for population surveillance. Covariates included
      acculturation indicators and established periodontitis risk factors. Survey
      estimation procedures took account of the complex sampling design. Adjusted
      multivariate binomial regression estimated prevalence ratios and 95% confidence
      limits (CLs). RESULTS: Unadjusted prevalence of moderate and severe periodontitis
      was 38.5% and ranged from 24.7% among Dominicans to 52.1% among Cubans. Adjusted
      prevalence ratios for subgroups relative to Dominicans were as follows: (1) 1.34
      (95% CL, 1.13-1.58) among South Americans; (2) 1.37 (95% CL, 1.17-1.61) among
      Puerto Ricans; (3) 1.43 (95% CL, 1.25-1.64) among Mexicans; (4) 1.53 (95% CL,
      1.32-1.76) among Cubans; and (5) 1.55 (95% CL, 1.35-1.78) among Central
      Americans. CONCLUSIONS: Heterogeneity in prevalence of moderate/severe
      periodontitis among Hispanic/Latino subpopulations was not explained by
      acculturation or periodontitis risk factors.

PMID- 24731698
TI  - Response to letter to the editor: regarding "copper deficiency and neuropathology
      related to the petrous bone".

PMID- 24731699
TI  - Trait anxiety and somatic concerns associate with increased mortality risk: a 23
      year follow-up in aging men.
AB  - PURPOSE: We aimed to examine the impact of anxiety and somatic concerns on the
      mortality risk during a 23-year follow-up of a representative sample of men.
      METHODS: Finnish men aged 42-61 years (n = 2388) were followed up for a median of
      23.4 years. Anxiety was assessed using baseline scores for the Minnesota
      Multiphasic Personality Inventory Psychasthenia subscale and somatic concerns
      were measured with the Hypochondriasis subscale. Mortality data were obtained
      from the National Population Register. RESULTS: All-cause, injury, disease,
      cardiovascular, and cancer mortalities were examined as endpoints. Adjustments
      were performed for age, smoking, alcohol consumption, physical activity, low- and
      high-density lipoprotein cholesterol, body mass index, systolic blood pressure, a
      history of cardiovascular disease, marital status, socioeconomic status, the
      Framingham Type A Behavior Pattern Scale, and life events during the 12 months
      before the baseline examination. Anxiety and somatic concerns predicted the all
      cause mortality risk after full adjustments for sociodemographic background,
      lifestyle factors, and descriptors of somatic health. Regarding other forms of
      mortality, the risk ratios were significant after full adjustments in anxiety for
      injury and in somatic concerns for disease death. CONCLUSIONS: This study
      supported previous findings of anxiety predicting the all-cause mortality risk in
      men. Somatic concerns are a novel factor that needs to be taken into account
      while examining associations between personality and the risk of increased
      mortality.

PMID- 24731700
TI  - Oxidative balance score and risk for incident prostate cancer in a prospective
      U.S. cohort study.
AB  - PURPOSE: Oxidative stress is defined as an imbalance between pro-oxidants and
      antioxidants. Previous research found that a single comprehensive oxidative
      balance score (OBS) that includes individual pro- and anti-oxidant exposures may
      be associated with various conditions (including prostate cancer) in the absence
      of associations with the individual factors. We investigated an OBS-incident
      prostate cancer association among 43,325 men in the Cancer Prevention Study II
      Nutrition Cohort. METHODS: From 1999-2007, 3386 incident cases were identified.
      Twenty different components, used in two ways (unweighted or weighted based on
      literature reviews), were incorporated into the OBS, and the resulting scores
      were then expressed as three types of variables (continuous, quartiles, or six
      equal intervals). Multivariable-adjusted rate ratios were calculated using Cox
      proportional hazards models. RESULTS: We hypothesized that the OBS would be
      inversely associated with prostate cancer risk; however, the rate ratios (95%
      confidence intervals) comparing the highest with the lowest OBS categories ranged
      from 1.17 (1.04-1.32) to 1.39 (0.90-2.15) for all cases, 1.14 (0.87-1.50) to 1.59
      (0.57-4.40) for aggressive disease (American Joint Committee on Cancer stage
      III/IV or Gleason score 8-10), and 0.91 (0.62-1.35) to 1.02 (1.02-1.04) for
      nonaggressive disease. CONCLUSIONS: Our findings are not consistent with the
      hypothesis that oxidative balance-related exposures collectively affect risk for
      prostate cancer.

PMID- 24731701
TI  - A qualitative process evaluation of electronic session-by-session outcome
      measurement in child and adolescent mental health services.
AB  - BACKGROUND: Regular monitoring of patient progress is important to assess the
      clinical effectiveness of an intervention. Recently, initiatives within UK child
      and adolescent mental health services (CAMHS) have advocated the use of session
      by-session monitoring to continually evaluate the patient's outcome throughout
      the course of the intervention. However, the feasibility and acceptability of
      such regular monitoring is unknown. METHOD: Semi-structured qualitative
      interviews were conducted with clinicians (n = 10), administrative staff (n = 8)
      and families (n = 15) who participated in a feasibility study of an electronic
      session-by-session outcome monitoring tool, (SxS), which is based on the
      Strengths and Difficulties Questionnaire (SDQ). This study took place in three
      CAMHS clinics in Nottinghamshire. The interview transcripts were thematically
      analysed. RESULTS: We found clinicians accepted the need to complete outcome
      measures, particularly valuing those completed by the patient. However, there
      were some difficulties with engaging clinicians in this practice and in the
      training offered. Generally, patients were supportive of completing SxS in the
      waiting room prior to the clinic session and assistance with the process from
      administrative staff was seen to be a key factor. Clinicians and families found
      the feedback reports created from SxS to be helpful for tracking progress,
      facilitating communication and engagement, and as a point of reflection. The use
      of technology was considered positively, although some technological difficulties
      hindered the completion of SxS. Clinicians and families appreciated the brevity
      of SxS, but some were concerned that a short questionnaire could not adequately
      encapsulate the complexity of the patient's issues. CONCLUSIONS: The findings
      show the need for appropriate infrastructure, mandatory training, and support to
      enable an effective system of session-by-session monitoring. Our findings
      indicate that clinicians, administrative staff and young people and their
      parents/carers would support regular monitoring if the system is easy to
      implement, with a standard 'clinic-wide' adoption of the procedure, and the
      resulting data are clinically useful.

PMID- 24731702
TI  - Targeted pancreatic cancer therapy with the small molecule drug conjugate SW IV
      134.
AB  - Pancreatic adenocarcinoma is highly resistant to conventional therapeutics and
      has been shown to evade apoptosis by deregulation of the X-linked and cellular
      inhibitors of apoptosis proteins (XIAP and cIAP). Second mitochondria-derived
      activator of caspases (Smac) induces and amplifies cell death by reversing the
      anti-apoptotic activity of IAPs. Thus, Smac-derived peptide analogues
      (peptidomimetics) have been developed and shown to represent promising cancer
      therapeutics. Sigma-2 receptors are overexpressed in many proliferating tumor
      cells including pancreatic cancer. Selected ligands to this receptor are rapidly
      internalized by cancer cells. These characteristics have made the sigma-2
      receptor an attractive target for drug delivery because selective delivery to
      cancer cells has the potential to increase therapeutic efficacy while minimizing
      toxicity to normal tissues. Here, we describe the initial characterization of SW
      IV-134, a chemically linked drug conjugate between the sigma-2 ligand SW43 and
      the Smac mimetic SW IV-52 as a novel treatment option for pancreatic
      adenocarcinoma. The tumor killing characteristics of our dual-domain therapeutic
      SW IV-134 was far greater than either component in isolation or in an equimolar
      mix and suggests enhanced cellular delivery when chemically linked to the sigma-2
      ligand. One of the key findings was that SW IV-134 retained target selectivity of
      the Smac cargo with the involvement of the NF-kappaB/TNFalpha signaling pathway.
      Importantly, SW IV-134 slowed tumor growth and improved survival in murine models
      of pancreatic cancer. Our data support further study of this novel therapeutic
      and this drug delivery strategy because it may eventually benefit patients with
      pancreatic cancer.

PMID- 24731703
TI  - Ultramorphological characteristics of mature larvae of Nitidula carnaria
      (Schaller 1783) (Coleoptera: Nitidulidae), a beetle species of forensic
      importance.
AB  - Beetles of the genus Nitidula Fabricius are forensically important, and their
      adults and larvae have been found associated with human corpses and animal
      carcasses in many places of the world. The external morphology of the larvae of
      Nitidula carnaria (Schaller 1783) was examined by scanning electron microscopy
      (SEM) to provide a description enabling identification of this forensically
      important species. The ultrastructure of the head was examined, antennae,
      mandibles, epipharynx, maxillary and labial palpi, spiracles, thorax, legs, and
      abdominal segments (especially segments 9 and 10); the tegument was also
      emphasised in this examination. Several types of sensilla were observed on the
      maxillary and labial palpi, including sensilla basiconica, sensilla styloconica,
      and perhaps a different type of sensilla digitiformia. In abdominal segment 10, a
      sensilla campaniformia was observed. Two types of plates were noticed in the
      abdominal tegument. The characteristics described here can be used to identify
      this species. No other study of the ultrastructure of Nitidulidae larvae is
      available for comparison. This is the first report of N. carnaria in carcasses in
      Chile. 

PMID- 24731704
TI  - Genomic composition and evolution of Aedes aegypti chromosomes revealed by the
      analysis of physically mapped supercontigs.
AB  - BACKGROUND: An initial comparative genomic study of the malaria vector Anopheles
      gambiae and the yellow fever mosquito Aedes aegypti revealed striking differences
      in the genome assembly size and in the abundance of transposable elements between
      the two species. However, the chromosome arms homology between An. gambiae and
      Ae. aegypti, as well as the distribution of genes and repetitive elements in
      chromosomes of Ae. aegypti, remained largely unexplored because of the lack of a
      detailed physical genome map for the yellow fever mosquito. RESULTS: Using a
      molecular landmark-guided fluorescent in situ hybridization approach, we mapped
      624 Mb of the Ae. aegypti genome to mitotic chromosomes. We used this map to
      analyze the distribution of genes, tandem repeats and transposable elements along
      the chromosomes and to explore the patterns of chromosome homology and
      rearrangements between Ae. aegypti and An. gambiae. The study demonstrated that
      the q arm of the sex-determining chromosome 1 had the lowest gene content and the
      highest density of minisatellites. A comparative genomic analysis with An.
      gambiae determined that the previously proposed whole-arm synteny is not fully
      preserved; a number of pericentric inversions have occurred between the two
      species. The sex-determining chromosome 1 had a higher rate of genome
      rearrangements than observed in autosomes 2 and 3 of Ae. aegypti. CONCLUSIONS:
      The study developed a physical map of 45% of the Ae. aegypti genome and provided
      new insights into genomic composition and evolution of Ae. aegypti chromosomes.
      Our data suggest that minisatellites rather than transposable elements played a
      major role in rapid evolution of chromosome 1 in the Aedes lineage. The research
      tools and information generated by this study contribute to a more complete
      understanding of the genome organization and evolution in mosquitoes.

PMID- 24731705
TI  - Elastin based cell-laden injectable hydrogels with tunable gelation, mechanical
      and biodegradation properties.
AB  - Injectable hydrogels made from extracellular matrix proteins such as elastin show
      great promise for various biomedical applications. Use of cytotoxic reagents,
      fixed gelling behavior, and lack of mechanical strength in these hydrogels are
      the main associated drawbacks. The aim of this study was to develop highly
      cytocompatible and injectable elastin-based hydrogels with alterable gelation
      characteristics, favorable mechanical properties and structural stability for
      load bearing applications. A thermoresponsive copolymer, poly(N
      isopropylacrylamide-co-polylactide-2-hydroxyethyl methacrylate-co-oligo(ethylene
      glycol)monomethyl ether methacrylate, was functionalized with succinimide ester
      groups by incorporating N-acryloxysuccinimide monomer. These ester groups were
      exploited to covalently bond this polymer, denoted as PNPHO, to different
      proteins with primary amine groups such as alpha-elastin in aqueous media. The
      incorporation of elastin through covalent bond formation with PNPHO promotes the
      structural stability, mechanical properties and live cell proliferation within
      the structure of hydrogels. Our results demonstrated that elastin-co-PNPHO
      solutions were injectable through fine gauge needles and converted to hydrogels
      in situ at 37  degrees C in the absence of any crosslinking reagent. By altering
      PNPHO content, the gelling time of these hydrogels can be finely tuned within the
      range of 2-15 min to ensure compatibility with surgical requirements. In
      addition, these hydrogels exhibited compression moduli in the range of 40-145
      kPa, which are substantially higher than those of previously developed elastin
      based hydrogels. These hydrogels were highly stable in the physiological
      environment with the evidence of 10 wt% mass loss in 30 days of incubation in a
      simulated environment. This class of hydrogels is in vivo bioabsorbable due to
      the gradual increase of the lower critical solution temperature of the copolymer
      to above 37  degrees C due to the cleavage of polylactide from the PNPHO
      copolymer. Moreover, our results demonstrated that more than 80% of cells
      encapsulated in these hydrogels remained viable, and the number of encapsulated
      cells increased for at least 5 days. These unique properties mark elastin-co
      PNHPO hydrogels as favorable candidates for a broad range of tissue engineering
      applications. 

PMID- 24731706
TI  - Gold nanoshells-mediated bimodal photodynamic and photothermal cancer treatment
      using ultra-low doses of near infra-red light.
AB  - Previously, gold nanoshells were shown to be able to effectively convert photon
      energy to heat, leading to hyperthermia and suppression of tumor growths in mice.
      Herein, we show that in addition to the nanomaterial-mediated photothermal
      effects (NmPTT), gold nanoshells (including, nanocages, nanorod-in-shell and
      nanoparticle-in-shell) not only are able to absorb NIR light, but can also emit
      fluorescence, sensitize formation of singlet oxygen and exert nanomaterial
      mediated photodynamic therapeutic (NmPDT) complete destruction of solid tumors in
      mice. The modes of NmPDT and NmPTT can be controlled and switched from one to the
      other by changing the excitation wavelength. In the in vitro experiments, gold
      nanocages and nanorod-in-shell show larger percentage of cellular deaths
      originating from NmPDT along with the minor fraction of NmPTT effects. In
      contrast, nanoparticle-in-shell exhibits larger fraction of NmPTT-induced
      cellular deaths together with minor fraction of NmPDT-induced apoptosis.
      Fluorescence emission spectra and DPBF quenching studies confirm the generation
      of singlet O2 upon NIR photoirradiation. Both NmPDT and NmPTT effects were
      confirmed by measurements of reactive oxygen species (ROS) and subsequent sodium
      azide quenching, heat shock protein expression (HSP 70), singlet oxygen sensor
      green (SOSG) sensing, changes in mitochondria membrane potential and apoptosis in
      the cellular experiments. In vivo experiments further demonstrate that upon
      irradiation at 980 nm under ultra-low doses (~150 mW/cm(2)), gold nanocages
      mostly exert NmPDT effect to effectively suppress the B16F0 melanoma tumor
      growth. The combination of NmPDT and NmPTT effects on destruction of solid tumors
      is far better than pure NmPTT effect by 808 nm irradiation and also doxorubicin.
      Overall, our study demonstrates that gold nanoshells can serve as excellent multi
      functional theranostic agents (fluorescence imaging + NmPDT + NmPTT) upon single
      photon NIR light excitation under ultra-low laser doses. 

PMID- 24731707
TI  - Fracture resistance of human cortical bone across multiple length-scales at
      physiological strain rates.
AB  - While most fracture-mechanics investigations on bone have been performed at low
      strain rates, physiological fractures invariably occur at higher loading rates.
      Here, at strain rates from 10(-5) to 10(-1) s(-1), we investigate deformation and
      fracture in bone at small length-scales using in situ small-angle x-ray
      scattering (SAXS) to study deformation in the mineralized collagen fibrils and at
      the microstructural level via fracture-mechanics experiments to study toughening
      mechanisms generating toughness through crack-tip shielding. Our results show
      diminished bone toughness at increasing strain rates as cracks penetrate through
      the osteons at higher strain rates instead of deflecting at the cement lines,
      which is a prime toughening mechanism in bone at low strain rates. The absence of
      crack deflection mechanisms at higher strain rates is consistent with lower
      intrinsic bone matrix toughness. In the SAXS experiments, higher fibrillar
      strains at higher strain rates suggest less inelastic deformation and thus
      support a lower intrinsic toughness. The increased incidence of fracture induced
      by high strain rates can be associated with a loss in toughness in the matrix
      caused by a strain rate induced stiffening of the fibril ductility, i.e., a
      "locking-up" of the viscous sliding and sacrificial bonding mechanisms, which are
      the origin of inelastic deformation (and toughness) in bone at small length
      scales. 

PMID- 24731708
TI  - Enhanced therapeutic efficacy of an adenovirus-PEI-bile-acid complex in tumors
      with low coxsackie and adenovirus receptor expression.
AB  - Adenovirus (Ad) is a potential vehicle for cancer gene therapy. However, cells
      that express low levels of the coxsackie and adenovirus receptor (CAR)
      demonstrate poor Ad infection efficiency. We developed a bile acid-conjugated
      poly(ethyleneimine) (DA3)-coated Ad complex (Ad/DA3) to enhance Ad transduction
      efficiency. The size distribution and zeta potential of Ad/DA3 increased to 324
      +/- 3.08 nm and 10.13 +/- 0.21 mV, respectively, compared with those of naked Ad
      (108 +/- 2.26 nm and -17.7 +/- 1.5 mV). The transduction efficiency of Ad/DA3
      increased in a DA3 polymer concentration-dependent manner. Enhanced gene transfer
      by Ad/DA3 was more evident in CAR-moderate and CAR-negative cancer cells.
      Competition assays with a CAR-specific antibody revealed that internalization of
      Ad/DA3 was not mediated primarily by CAR but involved clathrin-, caveolae-, and
      macropinocytosis-mediated endocytosis. Cancer cell death was significantly
      increased when oncolytic Ad and DA3 were complexed (RdB-KOX/DA3) compared to that
      of naked oncolytic Ad and was inversely proportional to CAR levels. Importantly,
      RdB-KOX/DA3 significantly enhanced apoptosis, reduced angiogenesis, reduced
      proliferation, and increased active viral replication in human tumor xenografts
      compared to that of naked Ad. These results demonstrate that a hybrid vector
      system can increase the efficacy of oncolytic Ad virotherapy, particularly in CAR
      limited tumors. 

PMID- 24731710
TI  - Structurally engineered anodic alumina nanotubes as nano-carriers for delivery of
      anticancer therapeutics.
AB  - Here, we report a study on the biocompatibility, cell uptake and in vitro
      delivery of tumor necrosis factor-related apoptosis-inducing ligand (Apo2L/TRAIL)
      by new nano-carriers called anodic alumina nanotubes (AANTs) for potential cancer
      therapy. AANTs were electrochemically engineered by a unique pulse anodization
      process, which enables precise control of the nanotube geometry, and used here as
      nano-carriers for drug delivery. In vitro cytotoxicity and cell uptake of AANTs
      was assessed using MDA-MB231-TXSA human breast cancer cells and mouse RAW 264.7
      macrophage cells. AANTs exhibited excellent biocompatibility in both cell lines
      over a time course of five days even at a maximum concentration of AANTs of 100
      MUgmL(-1). Transmission electron microscopy and fluorescence microscopy confirmed
      a significant uptake of AANTs by RAW 264.7 cells and breast cancer cells. AANTs
      loaded with the pro-apoptotic protein Apo2L/TRAIL showed exceptional loading
      capacity (104 +/- 14.4 MUgmg(-1) of AANTs) and demonstrated significant decrease
      in viability of MDA-MB231-TXSA cancer cells due to apoptosis induction. These
      results demonstrate that AANTs are promising nano-carriers for drug delivery
      applications. 

PMID- 24731709
TI  - Combined effect of strontium and zoledronate on hydroxyapatite structure and bone
      cell responses.
AB  - The influence of the simultaneous presence of the two inhibitors of bone
      degradation, strontium and zoledronate, on the direct synthesis of hydroxyapatite
      was explored in the range of Sr concentration up to 50 atom% at two different
      bisphosphonate concentrations (ZOL7 and ZOL14). The results of structural
      analysis indicated that HA can be obtained as a single crystalline phase up to a
      Sr concentration in solution of 20 and 10 atom% within the ZOL7 and ZOL14 series
      respectively. Both Sr substitution and ZOL incorporation affect the length of the
      coherently scattering crystalline domains and the dimensions of HA nanocrystals.
      At greater Sr content, XRD full profile fitting data indicate that zoledronate
      provokes the segregation of Sr in two crystalline apatitic phases, at different
      strontium content. Co-cultures of osteoblast-like MG63 cells and human osteoclast
      show that ZOL displays a greater inhibitory influence than Sr on osteoclast
      proliferation and activity. On the other hand, the results obtained on osteoblast
      surnatant and on gene expression indicate that Sr exerts a greater promotion on
      osteoblast proliferation and differentiation. The co-presence of Sr and ZOL has a
      combined effect on the differentiation markers, so that HA containing about 4 wt%
      ZOL and 4 Sr atom%, and even more HA containing about 4 wt% ZOL and 8 Sr atom%,
      result the best compromise for osteoblast promotion and osteoclast inhibition. 

PMID- 24731711
TI  - Cell surface engineering to enhance mesenchymal stem cell migration toward an SDF
      1 gradient.
AB  - Mesenchymal stem cell (MSC) therapy for the treatment of myocardial infarction
      (MI) has shown considerable promise in clinical trials. A billion MSCs need to be
      administered for therapeutic efficacy, however, because only ~1% of the cells
      reach the ischemic myocardium after systemic infusion. This is due to the loss of
      the homing signal on the surface of the MSCs during their expansion in culture.
      Stromal-derived factor-1 (SDF-1) is up-regulated immediately after infarction and
      is released into the peripheral blood. This SDF-1 reaches the bone marrow and
      recruits CXC chemokine receptor 4 (CXCR4)-positive stem cells. The CXCR4/SDF-1
      axis plays an important role in MSC homing to the ischemic myocardium. Since SDF
      1 is highly expressed for only 48 h after infarction, the current approaches
      requiring long-term culture of MSCs to induce CXCR4 expression are not clinically
      useful. To provide a clinically viable means to improve the homing of MSCs, we
      have developed a surface modification method to incorporate recombinant CXCR4
      protein on the membrane of MSCs within 10 min. Using this method, we have
      confirmed the improved migration of MSCs toward an SDF-1 gradient. 

PMID- 24731712
TI  - Synergistic effects of bisphosphonate and calcium phosphate nanoparticles on peri
      implant bone responses in osteoporotic rats.
AB  - The prevalence of osteoporosis will increase within the next decades due to the
      aging world population, which can affect the bone healing response to dental and
      orthopedic implants. Consequently, local drug targeting of peri-implant bone has
      been proposed as a strategy for the enhancement of bone-implant integration in
      osteoporotic conditions. In the present study, an established in-vivo femoral
      condyle implantation model in osteoporotic and healthy bone is used to analyze
      the osteogenic capacity of titanium implants coated with bisphosphonate (BP)
      loaded calcium phosphate nanoparticles (nCaP) under compromised medical
      conditions. After 4 weeks of implantation, peri-implant bone volume (%BV; by
      MUCT) and bone area (%BA; by histomorphometry) were significantly increased
      within a distance of 500 MUm from implant surfaces functionalized with BP
      compared to control implants in osteoporotic and healthy conditions.
      Interestingly, the deposition of nCaP/BP coatings onto implant surfaces increased
      both peri-implant bone contact (%BIC) and volume (%BV) compared to the deposition
      of nCaP or BP coatings individually, in osteoporotic and healthy conditions. The
      results of real-time PCR revealed similar osteogenic gene expression levels to
      all implant surfaces at 4-weeks post-implantation. In conclusion, simultaneous
      targeting of bone formation (by nCaP) and bone resorption (by BP) using nCaP/BP
      surface coatings represents an effective strategy for synergistically improvement
      of bone-implant integration, especially in osteoporotic conditions. 

PMID- 24731713
TI  - Generation dependent cancer targeting potential of poly(propyleneimine)
      dendrimer.
AB  - Dendrimer-mediated delivery of bioactive is a successful and widely explored
      concept. This paper desribes comparative data pertaining to generation dependent
      cancer targeting propensity of Poly(propyleneimine) (PPI) dendrimers. This debut
      report reportsthe drug targeting and antciancer potential of different dendrimer
      generations. PPI dendrimers of different generations (3.0G, 4.0G and 5.0G) were
      synthesized and loaded with Melphalan. Results from loading, hemolysis,
      hematologic, cytotoxicty and flow cytometry assay depicted that as the generation
      of dendrimer increased from fourth to fifth, the only parameter i.e. toxicty is
      increased exponentionally. However, others parameters, i.e. loading, sustained
      release behavior, and targeting efficacy increased negligibly. Kaplan-Meier
      survival curves clearly depicted comparable therapeutic potential of PPI4M with
      PPI5M. In vivo investigations in Balb/c mice again favored 4.0G PPI dendrimer to
      be preferable nanocarrier for anticancer drug delivery owing to analogous
      anticancer potential. The outcomes of the investigation evidently projects 4.0G
      PPI dendrimer over 3.0G and 5.0G dendrimer in respect of its drug delivery
      benefit as well as superior biocompatibility. Thus, much against the common
      belief, 4.0G PPI dendrimers may be considered to be optimum in respect of drug
      delivery precluding the use of much more toxic 5.0G PPI dendrimer, which offers
      no benefit over 4.0G. 

PMID- 24731715
TI  - Stimulation of bone regeneration following the controlled release of water
      insoluble oxysterol from biodegradable hydrogel.
AB  - Recently bone graft substitutes using bone morphogenetic proteins (BMPs) have
      been heralded as potential alternatives to traditional bone reconstruction
      procedures. BMP-based products, however, are associated with significant and
      potentially life-threatening side effects when used in the head and neck region
      and furthermore, are exorbitantly priced. Oxysterols, products of cholesterol
      oxidation, represent a class of molecules that are favorable alternatives or
      adjuncts to BMP therapy due to their low side effect profile and cost. In order
      to establish the optimal clinical utility of oxysterol, an optimal scaffold must
      be developed, one that allows the release of oxysterol in a sustained and
      efficient manner. In this study, we prepare a clinically applicable bone graft
      substitute engineered for the optimal release of oxysterol. We first solubilized
      oxysterol in water by making use of polymeric micelles using l-lactic acid
      oligomer (LAo) grafted gelatin. Then, the water-solubilized oxysterol was
      incorporated into a biodegradable hydrogel that was enzymatically degraded
      intracorporeally. In this manner, oxysterol could be released from the hydrogel
      in a degradation-driven manner. The water-solubilized oxysterol incorporated
      biodegradable hydrogel was implanted into rat calvarial defects and induced
      successful bone regeneration. The innovative significance of this study lies in
      the development of a bone graft substitute that couples the osteogenic activity
      of oxysterol with a scaffold designed for optimized oxysterol release kinetics,
      all of which lead to better repair of bone defects. 

PMID- 24731714
TI  - Micromolded gelatin hydrogels for extended culture of engineered cardiac tissues.
AB  - Defining the chronic cardiotoxic effects of drugs during preclinical screening is
      hindered by the relatively short lifetime of functional cardiac tissues in vitro,
      which are traditionally cultured on synthetic materials that do not recapitulate
      the cardiac microenvironment. Because collagen is the primary extracellular
      matrix protein in the heart, we hypothesized that micromolded gelatin hydrogel
      substrates tuned to mimic the elastic modulus of the heart would extend the
      lifetime of engineered cardiac tissues by better matching the native chemical and
      mechanical microenvironment. To measure tissue stress, we used tape casting,
      micromolding, and laser engraving to fabricate gelatin hydrogel muscular thin
      film cantilevers. Neonatal rat cardiac myocytes adhered to gelatin hydrogels and
      formed aligned tissues as defined by the microgrooves. Cardiac tissues could be
      cultured for over three weeks without declines in contractile stress. Myocytes on
      gelatin had higher spare respiratory capacity compared to those on fibronectin
      coated PDMS, suggesting that improved metabolic function could be contributing to
      extended culture lifetime. Lastly, human induced pluripotent stem cell-derived
      cardiac myocytes adhered to micromolded gelatin surfaces and formed aligned
      tissues that remained functional for four weeks, highlighting their potential for
      human-relevant chronic studies. 

PMID- 24731716
TI  - The effect of nitrogen limitation on acetyl-CoA carboxylase expression and fatty
      acid content in Chromera velia and Isochrysis aff. galbana (TISO).
AB  - Lipids from microalgae have become a valuable product with applications ranging
      from biofuels to human nutrition. While changes in fatty acid (FA) content and
      composition under nitrogen limitation are well documented, the involved molecular
      mechanisms are poorly understood. Acetyl-CoA carboxylase (ACCase) is a key enzyme
      in the FA synthesis and elongation pathway. Plastidial and cytosolic ACCases
      provide malonyl-CoA for de novo FA synthesis in the plastid and FA elongation in
      the endoplasmic reticulum, respectively. The present study aimed at investigating
      the expression of plastidial and cytosolic ACCase in Chromera velia and
      Isochrysis aff. galbana (TISO) and their impact on FA content and elongation
      level when grown under nitrogen-deplete conditions. In C. velia, plastidial
      ACCase was significantly upregulated during nitrogen starvation and with culture
      age, strongly correlating with increased FA content. Conversely, plastidial
      ACCase of I. aff. galbana was not differentially expressed in nitrogen-deplete
      cultures, but upregulated during the logarithmic phase of nitrogen-replete
      cultures. In contrast to plastidial ACCase, the cytosolic ACCase of C. velia was
      downregulated with culture age and nitrogen-starvation, strongly correlating with
      an increase in medium-chain FAs. In conclusion, the expression of plastidial and
      cytosolic ACCase changed with growth phase and nutrient status in a species
      specific manner and nitrogen limitation did not always result in FA accumulation.

PMID- 24731717
TI  - Single nucleotide polymorphism scanning and expression of the FRZB gene in pig
      populations.
AB  - Secreted frizzled-related protein 3 (sFRP3), encoded by the gene FRZB, is a
      member of the sFRP family with important roles in inhibition of the Wnt
      signalling pathway through competitive binding of the Wnt receptor. Here, we
      investigated pig FRZB as a candidate gene for growth traits and identified three
      polymorphic sites, an insertion (A-532B) and two SNPs (G636A and C650T) in its 5'
      UTR. The genotype distributions of G636A and C650T were significantly different
      among mini-type indigenous (Diannan Small-ear and Tibetan), normal indigenous
      (Laiwu and Huai), and introduced (Large Yorkshire and Landrace) breeds. In semi
      quantitative PCR expression analysis, expression of FRZB mRNA was abundant in
      tissues of hypophysis, longissimus dorsi muscle, and adipose tissues, and low in
      the heart, hypothalamus, and brain. Quantitative determination of mRNA level and
      protein expression analysis were corresponding. The results demonstrated that
      FRZB gene expression in longissimus dorsi muscle and liver tissue was
      significantly higher in Diannan Small-ear and Tibetan pigs than in the Large
      Yorkshire breed (P<0.05); however, in back fat tissue, the expression was
      significantly higher in Diannan Small-ear pig than in Tibetan or Large Yorkshire
      breeds (P<0.05). Given the known growth and fat characteristics of the breeds,
      these results indicate that FRZB expression has a negative association with
      muscle growth and a positive association with fat deposition. In conclusion, FRZB
      may be a major candidate gene for growth traits in pigs.

PMID- 24731718
TI  - The production of Neptunium-236g.
AB  - Radiochemical analysis of (237)Np is important in a number of fields, such as
      nuclear forensics, environmental analysis and measurements throughout the nuclear
      fuel cycle. However analysis is complicated by the lack of a stable isotope of
      neptunium. Although various tracers have been used, including (235)Np, (239)Np
      and even (236)Pu, none are entirely satisfactory. However, (236g)Np would be a
      better candidate for a neptunium yield tracer, as its long half-life means that
      it is useable as both a radiometric and mass spectrometric measurements. This
      radionuclide is notoriously difficult to prepare, and limited in scope. In this
      paper, we examine the options for the production of (236g)Np, based on work
      carried out at NPL since 2011. However, this work was primarily aimed at the
      production of (236)Pu, and not (236g)Np and therefore the rate of production are
      based on the levels of (236)Pu generated in the irradiation of (i) (238)U with
      protons, (ii) (235)U with deuterons, (iii) (236)U with protons and (iv) (236)U
      with deuterons. The derivation of a well-defined cross section is complicated by
      the relevant paucity of information on the variation of the (236m)Np:(236g)Np
      production ratio with incident particle energy. Furthermore, information on the
      purity of (236g)Np so produced is similarly sparse. Accordingly, the existing
      data is assessed and a plan for future work is presented. 

PMID- 24731719
TI  - Barriers and facilitators to evidence-use in program management: a systematic
      review of the literature.
AB  - BACKGROUND: The use of evidence in decision-making at the program management
      level is a priority in health care organizations. The objective of this study was
      to identify potential barriers and facilitators experienced by managers to the
      use of evidence in program management within health care organizations. METHODS:
      The authors conducted a comprehensive search for published, peer-reviewed and
      grey literature that explores the use of evidence in program management. Two
      reviewers selected relevant studies from which data was extracted using a
      standard data abstraction form and tabulated for qualitative analysis. The
      results were summarized through narrative review. The quality of the included
      studies was assessed using published criteria for the critical appraisal of
      qualitative, quantitative and mixed methods research. RESULTS: Fourteen papers
      were included in the review. Barriers and facilitators were categorized into five
      main thematic areas: (1) Information, (2) Organization--Structure and Process,
      (3) Organization--Culture, (4) Individual, and (5) Interaction. CONCLUSION: This
      paper reviews the literature on barriers and facilitators to evidence-informed
      decision-making experienced by program management decision-makers within health
      care organizations. The multidimensional solutions required to promote evidence
      informed program management can be developed through an understanding of the
      existing barriers and facilitators of evidence-use.

PMID- 24731720
TI  - Editorial overview: bioinorganic chemistry: recent advances in bioinorganic
      chemistry.

PMID- 24731721
TI  - Multiple sclerosis: clinical features and MRI findings in Northern China.
AB  - BACKGROUND: Reports in Asian populations suggest that ethnic and geographical
      differences may influence susceptibility to multiple sclerosis (MS) and its
      clinical behaviors. Here, we sought to retrospectively survey clinical
      characteristics and MRI data in Chinese subjects with MS. METHODS: We conducted a
      retrospective analysis in 117 patients with MS. The patients were divided into
      subgroups with optic-spinal form of multiple sclerosis (OSMS; n = 42) and
      classical multiple sclerosis (CMS; n = 75). Clinical characteristics, MRI finding
      and expanded disability status scale (EDSS) score were compared between the two
      groups. RESULTS: In 117 MS patients, 64.1% patients were classified as having CMS
      and 35.9% OSMS forms. White blood cell counts of OSMS patients were significantly
      higher than those of CMS patients (P <0.05). The longitudinal fusion lesions of
      spinal cord on MRI were statistically significant between groups (P <0.05).
      Spinal cord MRI showed that MS lesions were longer, and revealed spinal cord
      swelling in patients with CMS, but atrophy in patients with OSMS. The EDSS score
      at five years was significantly higher in patients with OSMS than in those with
      CMS (P <0.05). Relapse rates of patients with OSMS were also higher than those of
      patients with CMS (P <0.01) within one to three years. CONCLUSIONS: OSMS accounts
      for a higher proportion of MS populations in Northern China than in Western
      countries. MRI showed a longitudinally extensive spinal cord lesion in patients
      with OSMS and spinal cord swelling at onset.

PMID- 24731722
TI  - DNA methylation study of fetus genome through a genome-wide analysis.
AB  - BACKGROUND: DNA methylation is a crucial epigenetic modification of the genome
      which is involved in embryonic development, transcription, chromatin structure, X
      chromosome inactivation, genomic imprinting and chromosome stability. Consistent
      with these important roles, DNA methylation has been demonstrated to be required
      for vertebrate early embryogenesis and essential for regulating temporal and
      spatial expression of genes controlling cell fate and differentiation. Further
      studies have shown that abnormal DNA methylation is associated with human
      diseases including the embryonic development diseases. We attempt to study the
      DNA methylation status of CpG islands in fetus related to fetus growth and
      development. METHODS: GeneChip(r) Human Tiling 2.0R Array set is used for
      analysis of methylated DNA in a whole-genome wide in 8 pairs amniotic fluid and
      maternal blood DNA samples. RESULTS: We found 1 fetus hypermethylation DNA
      markers and 4 fetus hypomethylation DNA markers though a Genome-wide analysis.
      These DNA markers all found to be associated with the critical genes for fetus
      growth and development (SH2D3C gene, EML3 gene, TRIM71 gene, HOXA3 gene and HOXA5
      gene). CONCLUSIONS: These genes can be used as a biomarker for association
      studying of embryonic development, pathological pregnancy and so on. The present
      study has provided new and fundamental insights into the roles that DNA
      methylation has in embryonic development and in the pathological pregnancy.

PMID- 24731723
TI  - Leukocyte telomerase activity and antidepressant efficacy in bipolar disorder.
AB  - Telomeres are DNA-protein complexes that cap linear DNA strands, protecting DNA
      from damage. Recently, shorten telomeres length has been reported in bipolar
      disorder (BD) and depression. The enzyme telomerase regulates telomeres' length,
      which has been associated with cellular viability; however it is not clear how
      telomerase may be involved in the pathophysiology and therapeutics of BD. In the
      present study, leukocyte telomerase activity was assessed in 28 medication-free
      BD depressed individuals (DSM-IV-TR criteria) at baseline and after 6 weeks of
      lithium therapy (n=21) also matching with 23 healthy controls. There was no
      difference between telomerase activity in subjects with BD depression (before or
      after lithium) and controls. Improvement of depressive symptoms was negatively
      associated with telomerase activity after 6 weeks of lithium therapy. This is the
      first study describing telomerase activity in BD research. Overall, telomerase
      activity seems not directly involved in the pathophysiology of short-term BD.
      Lithium's antidepressant effects may involve regulation at telomerase activity.
      Further studies with larger samples and long-term illness are also warranted. 

PMID- 24731724
TI  - Closed chain assessment of quadriceps activation using the superimposed burst
      technique.
AB  - The superimposed burst technique is used to estimate quadriceps central
      activation ratio during a maximal voluntary isometric contraction, which is
      calculated from force data during an open-chain knee extension task. Assessing
      quadriceps activation in a closed-chain position would more closely simulate the
      action of the quadriceps during activity. Our aim was to determine the test
      retest reliability of the quadriceps central activation ratio in the closed
      chain. METHODS: Twenty-two healthy, active volunteers (13M/12F; age=23.8+/-3;
      height=72.7+/-14.5cm; mass=175.3+/-9.6kg) were recruited to participate. Knee
      extension MVIC torque and the peak torque during a superimposed electrical
      stimulus delivered to the quadriceps during an MVIC were measured to estimate
      quadriceps CAR. Interclass correlation coefficients were used to assess test
      retest reliability between sessions, and Bland-Altman plots to graphically assess
      agreement between sessions. RESULTS: Test-retest reliability was fair for CAR
      (ICC2,k=0.68; P=0.005), with a mean difference of -2.8+/-10.3%, and limits of
      agreement ranging -23.1-18.1%. CONCLUSIONS: CAR calculated using the superimposed
      burst technique is moderately reliable in a closed-chain position using technique
      based instruction. Although acceptable reliability was demonstrated, wide limits
      of agreement suggest high variability between sessions.

PMID- 24731725
TI  - Abstracts of the 69th Annual Scientific Meeting of the Society of Biological
      Psychiatry, May 8-12, 2014, New York City, New York.

PMID- 24731726
TI  - A survey of retirement intentions of Baby Boomers: an overview of health, social
      and economic determinants.
AB  - BACKGROUND: Governments have been implementing policies aimed at halting the
      trend towards early retirement for Baby Boomers. Public policies can have a
      strong effect on when a person retires and this analysis contributes to an
      improved understanding of retirement aspirations in regards to health, social,
      workplace and economic determinants. METHODS: In October 2011 a telephone survey
      was undertaken with participants aged 50 to 65 years who were in paid employment
      and who had been in the workforce for the previous three years. Participants were
      obtained from two identical South Australian cohort studies - the North West
      Adelaide Health Study and the Florey Adelaide Male Ageing Study. The results of
      the telephone survey were linked to the original cohort data. Data were weighted
      by sex, age, postcode and probability of selection in the household. Work related
      questions included how much they thought about their retirement, current
      occupation, employment status, type of workplace and hours worked per week.
      Health related questions included current smoking status, physical activity, body
      mass index, self-reported health status and overall life satisfaction. Uni
      variable and multi-variable analyses were undertaken to compare the different
      associations between people who were and were not intending to retire. RESULTS:
      In total, 25.9% (n = 210) of people who were currently in paid employment
      indicated that they intend to retire completely from the workforce. The remainder
      indicated that they will continue to work (41.8% retire from full-time work but
      work part-time, 25.7% continue working part-time but reduce their current hours,
      and 6.7% never retire). The multi-variable results indicate that those with lower
      education, having a savings habit, and sales workers more likely to anticipate
      complete retirement. The self-employed, and those thinking only moderately about
      retirement, were more likely to extend their working life beyond age 65.
      CONCLUSION: An important finding of this study is the large number of Baby
      Boomers who indicated that they would be happy to work part-time or never retire.
      Policies and continued dialogue aimed at making the workplace a safe, flexible
      and welcoming environment to accommodate this wish, and to entice others to take
      up this option over complete withdrawal from the labour force, is required.

PMID- 24731727
TI  - Colonic endoscopic mucosal resection of large polyps: Is it safe in the very
      elderly?
AB  - BACKGROUND: Outcomes on colon endoscopic mucosal resection in the very elderly
      patient population are unknown. AIMS: Aims of this study were to evaluate the
      outcomes and safety of colon endoscopic mucosal resection in this target
      population. METHODS: Observational, retrospective study of patients >= 80 years
      of age that underwent colon endoscopic mucosal resection >= 2 cm. Demographics,
      American Society of Anesthesiologists classification, procedural data, and
      surgical treatment data were collected. RESULTS: One-hundred-and-thirty-one colon
      endoscopic mucosal resections were performed on 99 patients >= 80 years of age
      with a mean age of 84. The majority of American Society of Anesthesiologists
      class was II. Mean lesion size was 3.3 cm (range, 2-12.5 cm), more procedures
      were performed in the right colon and adenoma/tubulovillous adenoma was the most
      common pathology. En bloc resection was performed on 26.7% of polyps (N=35).
      Eight procedure-related adverse events (8/131, 6.1%) occurred. No anaesthesia
      related adverse events or deaths occurred. Six patients required a colonic
      operation, and overall, 94% of the patient cohort evaded a colon operation.
      CONCLUSIONS: Colon endoscopic mucosal resection in very elderly patients can be
      performed at experienced endoscopy centres with a low rate of complications and
      offers these patients a non-surgical option of management of colorectal lesions.

PMID- 24731728
TI  - Muscle strength in adolescent men and risk of cardiovascular disease events and
      mortality in middle age: a prospective cohort study.
AB  - BACKGROUND: Ischemic heart disease and stroke are two severe types of
      cardiovascular disease (CVD), a major contributor to the global burden of
      disease. The preventive framework currently includes promotion of both adequate
      cardiorespiratory and muscular fitness. Although muscle fitness is established as
      an indicator of health, it is currently unknown whether muscle strength is
      associated with later CVD independently of cardiorespiratory fitness. METHODS: We
      studied 38,588 Swedish men who in 1969 to 1970 (typically aged 18 years)
      completed compulsory conscription. Using the mean standardized score of three
      isometric muscle strength tests performed at conscription (hand grip, elbow
      flexion and knee extension), we categorized the subjects into three groups with
      the 25th to 75th percentile defining the reference category. We followed the
      cohort until 2012 for diagnosed CVD events and mortality via national health care
      registers and the national cause of death register. To estimate hazard ratios
      (HR) for CVD events (coronary heart disease or stroke) and CVD mortality we used
      Cox proportional hazard models adjusted for body mass index, smoking, alcohol
      consumption, cardiorespiratory fitness and socioeconomic status. RESULTS: Men
      with high muscle strength in adolescence had a decreased risk of later CVD events
      (HR 0.88, 95% confidence interval 0.77 to 0.99), whereas we observed no increased
      risk in men with low muscle strength (0.99, 0.86 to 1.13). However, low muscle
      strength was associated with increased risk of CVD mortality during middle age
      (1.31, 1.02 to 1.67). CONCLUSIONS: Muscle strength in adolescent men is inversely
      associated with later CVD events and CVD mortality in middle age, independently
      of cardiorespiratory fitness and other important confounders. Thus, the role of
      muscle fitness in the prevention and pathogenesis of CVD warrants increased
      attention.

PMID- 24731729
TI  - hCG in screening for aneuploidy: a possible role for its glycoforms?
AB  - Fetal trisomy 21 is associated with elevated maternal serum hCG and its free beta
      subunit (hCG-beta) in vivo, and abnormal placental hCG production and
      glycosylation in vitro. Other maternal serum markers may also be disrupted in
      major aneuploidies (T21, T18, T13). We evaluated our aneuploidy screening
      practices, focusing on hCG-beta and hCG glycoforms, and retrospectively analyzed
      55 aneuploidy cases diagnosed over a 2 year period, determining maternal serum
      hCG glycoforms profiles using 2D-electrophoresis. Screening efficiency reached
      96.7%. T21 was associated with elevated hCG-beta while T18 presented with
      diminished serum markers. hCG glycoforms tended to be basic in aneuploidy (mainly
      T13).

PMID- 24731730
TI  - Carbon monoxide attenuates bacteria-induced Endothelin-1 expression in second
      trimester placental explants.
AB  - INTRODUCTION: The pro-inflammatory mediator and potent vasoconstrictor Endothelin
      1 (ET-1) is known to be expressed in the placenta. We have recently demonstrated
      that very low, non-toxic doses of carbon monoxide (CO), prevented infection
      induced preterm birth in mice. However the effect(s) of CO on human gestational
      tissues is yet to be fully explored. We hypothesize that CO will have a
      protective role against inflammation-induced E. coli by down-regulating the ET
      axis in placental explants. METHODS: Twenty placentas from elective termination
      of pregnancy in the second trimester were analyzed with or without exposure to
      heat killed E. coli over the course of 30 h. Placental ET-1, along with its
      biologically inactive precursor Big ET-1, and Endothelin Converting Enzyme-1 (ECE
      1, responsible for the cleavage of Big ET-1 to ET-1), were analyzed by ELISA.
      Gene expression for ET-1 (EDN1), ECE-1 and the ETA receptor (EDNRA) were analyzed
      using qPCR. Localization of ET-1 expression was also demonstrated using
      immunohistochemistry. RESULTS: E. coli significantly increased ET-1 transcription
      and secretion of BIG ET-1 and ET-1 in a time dependant manner which was
      ameliorated when exposed to CO at later time points. In the presence of CO, mRNA
      levels of ECE-1 were significantly reduced at 3 and 24 h, while EDNRA was
      significantly reduced at 6 and 18 h. CONCLUSIONS: Up-regulation of ET-1
      production in human placenta in the setting of infection can be attenuated by low
      doses of CO. Our results further explore the anti-inflammatory and regulatory
      mechanism(s) of CO on the ET axis components at the maternal fetal interface.

PMID- 24731731
TI  - Preparation, optimization and in vitro characterization of stearoyl-gemcitabine
      polymeric micelles: a comparison with its self-assembled nanoparticles.
AB  - Although gemcitabine (Gem) constitutes first-line therapy for pancreatic cancer,
      its clinical outcome suffers from rapid metabolism and acquired drug resistance.
      To overcome its limitations, several lipophilic prodrugs including 4-(N)-stearoyl
      Gem (GemC18) have been studied for their efficacy over Gem. Herein, we aimed to
      prepare and characterize the GemC18-loaded poly(ethylene glycol)-poly(d,l
      lactide) (PEG-PLA) polymeric micelles (PMs) as well as its self-assembled
      nanoparticles (NPs). A D-optimal design was also utilized to investigate the
      effects of formulation variables, namely initial drug/polymer ratio, total solid
      content, and the type of organic solvent on properties of GemC18-loaded PMs. The
      optimized formulation showed a particle size of about 120 nm, encapsulation
      efficiency >90%, and a sustained release behavior of the drug. Alternatively, the
      prodrug NPs were harvested in larger size (~300 nm) and more negative zeta
      potential, but less chemical stability compared to the optimized PMs. In Panc-1
      and AsPC-1 cell lines, both GemC18-loaded PMs and NPs were significantly more
      cytotoxic than GemC18 solution. Chiefly, they could effectively reduce the
      viability of Gem high-resistant AsPC-1 cells in culture, whereas the molar
      equivalent doses of Gem did not show any acceptable cytotoxicity. Thus, these
      results suggest a promising direction for alternative Gem delivery systems for
      future therapeutic applications.

PMID- 24731732
TI  - Bond strength and Raman analysis of the zirconia-feldspathic porcelain interface.
AB  - STATEMENT OF PROBLEM: Zirconia has the best mechanical properties of the
      available ceramic systems. However, the stability of the zirconia-feldspathic
      porcelain interface may be jeopardized by the presence of the chipping and
      debonding of the feldspathic porcelain. PURPOSE: The purpose of this study is to
      evaluate the shear bond strength of 3 cold isostatic pressed zirconia materials
      and a feldspathic veneer by analyzing their interface with micro-Raman
      spectroscopy. MATERIAL AND METHODS: The test groups were experimental zirconia,
      Zirkonzahn zirconia, and Schuetz zirconia. Blocks of partially sintered zirconia
      were cut into disks (n=20) and then veneered with a feldspathic porcelain. Half
      of the specimens from each group (n=10) were incubated in 37 degrees C water for
      24 hours, and the other half were thermocycled. All the specimens were then
      subjected to shear testing. The fractured areas were analyzed with optical
      stereomicroscopy and classified as adhesive, cohesive, or an adhesive-cohesive
      failure. Spectral patterns were examined to detect bands related to the zirconia
      and feldspathic porcelain phases. The shear strength data were submitted to 2-way
      ANOVA. RESULTS: No significant differences in shear bond strength were observed
      among the 3 groups, regardless of whether or not the specimens were thermocycled.
      Adhesive failures were the most prevalent types of failure (70%). Raman spectra
      were clearly distinguished for all the materials, which showed the presence of
      tetragonal and monoclinic phases. CONCLUSIONS: The controlled production of the
      experimental zirconia did not influence the results of the bond strength. Raman
      analysis suggested a process of interdiffusion by the presence of peaks
      associated with the zirconia and feldspathic ceramics.

PMID- 24731733
TI  - Young people's perception of sexual and reproductive health services in Kenya.
AB  - BACKGROUND: Addressing the Sexual and Reproductive Health (SRH) needs of young
      people remains a big challenge. This study explored experiences and perceptions
      of young people in Kenya aged 10-24 with regard to their SRH needs and whether
      these are met by the available healthcare services. METHODS: 18 focus group
      discussions and 39 in-depth interviews were conducted at health care facilities
      and youth centres across selected urban and rural settings in Kenya. All
      interviews were tape recorded and transcribed. Data was analysed using the
      thematic framework approach. RESULTS: Young people's perceptions are not uniform
      and show variation between boys and girls as well as for type of service
      delivery. Girls seeking antenatal care and family planning services at health
      facilities characterise the available services as good and staff as helpful.
      However, boys perceive services at health facilities as designed for women and
      children, and therefore feel uncomfortable seeking services. At youth centres,
      young people value the non-health benefits including availability of recreational
      facilities, prevention of idleness, building of confidence, improving
      interpersonal communication skills, vocational training and facilitation of
      career progression. CONCLUSION: Providing young people with SRH information and
      services through the existing healthcare system, presents an opportunity that
      should be further optimised. Providing recreational activities via youth centres
      is reported by young people themselves to not lead to increased uptake of SRH
      healthcare services. There is need for more research to evaluate how perceived
      non-health benefits young people do gain from youth centres could lead to
      improved SRH of young people.

PMID- 24731734
TI  - Planning for human papillomavirus (HPV) vaccination in sub-Saharan Africa: a
      modeling-based approach.
AB  - BACKGROUND: Human papillomavirus (HPV) vaccines have the potential to reduce
      cervical cancer incidence and mortality, particularly in the parts of the
      developing world that bear the greatest burden of disease. This research sought
      to predict the impact and cost-effectiveness of an HPV vaccination program in an
      example low-resource country with a high burden of cervical cancer: Mali, West
      Africa. METHODS: Novel compartmental mathematical models projected the impact of
      adolescent HPV vaccination in urban and rural areas of Mali. The models accounted
      for two high-risk vaccine-types: HPV 16 and 18. We then attached comprehensive
      real cost and cost-effectiveness estimates. RESULTS: Our models predict that HPV
      vaccination in Mali will reduce cervical cancer burden by a factor roughly equal
      to vaccine coverage. A point vaccination program was simulated in a cohort of
      333,146 urban and 588,982 rural Malian women, age 10-14. Vaccination of 50% of
      girls reduced the peak prevalence of HPV 16/18 to 5.0% in the urban setting and
      9.6% in the rural setting, down from 11.7% and 22.0%, respectively, with no
      vaccination. The 50% vaccination scenario averted 1145 cervical cancer deaths in
      the urban group and 2742 in the rural group. The cost per discounted life-year
      saved in this scenario was 1030 US dollars (urban) and 725 dollars (rural). The
      cost per life-year saved was higher at 90% coverage, but was still in the range
      of a "cost-effective" public health intervention. CONCLUSIONS: This research
      yielded the most comprehensive real cost estimates of HPV vaccination yet
      published for sub-Saharan Africa. Our models indicate that HPV vaccination in
      Mali will be cost-effective when introduced. To maximize the benefit using
      limited resources, vaccination programs may begin with a target coverage of about
      50%. We anticipate that costs of reaching late adopters after the First
      Vaccinated Wave of vaccination will be higher, but worthwhile.

PMID- 24731735
TI  - Investigating the relationship between mitochondrial genetic variation and
      cardiovascular-related traits to develop a framework for mitochondrial phenome
      wide association studies.
AB  - BACKGROUND: Mitochondria play a critical role in the cell and have DNA
      independent of the nuclear genome. There is much evidence that mitochondrial DNA
      (mtDNA) variation plays a role in human health and disease, however, this area of
      investigation has lagged behind research into the role of nuclear genetic
      variation on complex traits and phenotypic outcomes. Phenome-wide association
      studies (PheWAS) investigate the association between a wide range of traits and
      genetic variation. To date, this approach has not been used to investigate the
      relationship between mtDNA variants and phenotypic variation. Herein, we describe
      the development of a PheWAS framework for mtDNA variants (mt-PheWAS). Using the
      Metabochip custom genotyping array, nuclear and mitochondrial DNA variants were
      genotyped in 11,519 African Americans from the Vanderbilt University
      biorepository, BioVU. We employed both polygenic modeling and association testing
      with mitochondrial single nucleotide polymorphisms (mtSNPs) to explore the
      relationship between mtDNA variants and a group of eight cardiovascular-related
      traits obtained from de-identified electronic medical records within BioVU.
      RESULTS: Using polygenic modeling we found evidence for an effect of mtDNA
      variation on total cholesterol and type 2 diabetes (T2D). After performing
      comprehensive mitochondrial single SNP associations, we identified an increased
      number of single mtSNP associations with total cholesterol and T2D compared to
      the other phenotypes examined, which did not have more significantly associated
      SNPs than would be expected by chance. Among the mtSNPs significantly associated
      with T2D we identified variant mt16189, an association previously reported only
      in Asian and European-descent populations. CONCLUSIONS: Our replication of
      previous findings and identification of novel associations from this initial
      study suggest that our mt-PheWAS approach is robust for investigating the
      relationship between mitochondrial genetic variation and a range of phenotypes,
      providing a framework for future mt-PheWAS.

PMID- 24731736
TI  - 25 year survival outcomes for squamous cell carcinomas of the head and neck:
      population-based outcomes from a Canadian province.
AB  - OBJECTIVES: Long term outcomes of patients with head and neck cancer (HNC) are
      rarely reported, but of potential benefit to clinicians and researchers. Squamous
      cell carcinomas (SCC) of the head and neck represent a heterogeneous group of
      cancers. The purpose of this population based study is to describe primary site
      specific, long term outcomes of HNC. METHODS: All patients from a Canadian
      province diagnosed between 1986 and 1990 with SCC of the oral cavity, pharynx,
      and larynx were identified. Chart review and patient data were abstracted through
      the provincial cancer registry database. Survival analysis was performed with
      Kaplan Meier methods, while differences in survival between groups were assessed
      with log-rank tests. Multivariable analysis was performed using Cox-regression.
      RESULTS: 1657 patients were analyzed during the study period. Almost half (50.9%)
      of the cases were advanced stage (stage III IV) at presentation. Two, 5, 15 &
      25year overall survival (OS) and HNC specific survival for all the patients were
      64%, 46%, 21%, 11% and 74%, 63%, 53% & 49%, respectively. OS and HNC-specific
      mortality were statistically inferior among men, older age at diagnosis, advanced
      stages of disease, and was primary cancer site specific, with worse survival in
      oropharyngeal & hypopharyngeal sites, p<0.001. CONCLUSIONS: Survival rates vary
      by primary HNC site, and the overall survival & HNC specific survival differ over
      this long follow up assessment. Head and neck cancer specific death is most
      common in the first five years, and is subsequently dominated by competing causes
      of mortality. These results are useful as a reference tool for clinicians,
      researchers, and trainees.

PMID- 24731737
TI  - Quality of life in urban and rural settings: a study of head and neck cancer
      survivors.
AB  - OBJECTIVE: Urban-rural variation in cancer incidence, treatment, and clinical
      outcomes has been well researched. With the growing numbers and longer lifespan
      of cancer survivors, quality of life (QOL) is now a critical issue. The present
      study investigates the QOL of head and neck cancer (HNC) survivors in Ireland,
      paying special attention to urban and rural variation. METHODS: From the
      population-based National Cancer Registry Ireland, we identified 991 survivors of
      HNC (ICD10 C00-C14, C32), who were at least eight months post-diagnosis, and
      invited them to complete a postal survey. We used self-reported data and
      information from the Registry to create a composite variable classifying
      respondents' current area of residence as "urban" or "rural." Respondents self
      reported QOL using the Functional Assessment for Cancer Therapy with Head and
      Neck module (FACT-HN). We used bootstrap linear regression to control for
      confounding variables, while estimating the association of urban and rural
      residence to FACT-HN domain scores. RESULTS: We obtained survey and Registry data
      from 583 HNC survivors. Controlling for demographic and clinical variables, rural
      survivors reported higher physical (coefficient 1.27, bias-corrected and
      accelerated 95% confidence interval 0.54, 2.43), emotional (coef. 0.99, 95% CI
      0.21, 2.02), and HNC-specific (coef. 1.55, 95% CI 0.32, 3.54) QOL than their
      urban counterparts. Social and functional QOL did not differ significantly.
      CONCLUSIONS: These findings add to growing evidence of important differences in
      life experiences of cancers survivors in urban and rural settings. Results such
      as these will allow health professionals, policy makers and service providers to
      better serve these populations.

PMID- 24731739
TI  - Approach to the hemodialysis patient with an abnormal serum bicarbonate
      concentration.
AB  - We present a patient receiving hemodialysis with a persistently high serum
      bicarbonate concentration to illustrate the evaluation and management issues for
      patients with both high (>25 mEq/L) and low (<20 mEq/L) pretreatment values.
      Patients with high serum bicarbonate concentrations typically are malnourished
      and have low rates of endogenous acid production. Evaluation should begin with
      assessment of whether an acute and potentially reversible cause of metabolic
      alkalosis is present. If not, management should be directed at treating
      malnutrition. By contrast, patients with low predialysis serum bicarbonate
      concentrations, in the absence of an acute and reversible cause, may benefit from
      increasing the level by an adjustment in dialysate bicarbonate concentration.
      However, the level at which one should intervene and to what extent serum
      bicarbonate concentration should be increased are unresolved issues. Whether such
      an intervention will reduce mortality risk has not been determined.

PMID- 24731738
TI  - Potentially preventable hospitalization as a complication of CKD: a cohort study.
AB  - BACKGROUND: Ambulatory care-sensitive conditions have been described as those
      that (if appropriately managed in an outpatient setting) generally do not require
      subsequent hospitalization. Our goal was to identify clinical populations of
      people who are at the highest risk of ambulatory care-sensitive conditions
      related to chronic kidney disease (CKD). STUDY DESIGN: Retrospective cohort
      study. SETTING & PARTICIPANTS: 2,003,054 adults (including 238,747 adults with
      CKD) residing in Alberta, Canada, with at least one serum creatinine measurement
      between 2002 and 2009. PREDICTORS: Estimated glomerular filtration rate and
      albuminuria categories, CKD status, demographics, and clinical characteristics.
      OUTCOMES: Hospitalization with heart failure, hyperkalemia, volume overload, or
      malignant hypertension. MEASUREMENTS: We used the Alberta Kidney Disease Network
      database, which incorporates data from Alberta Health, the Northern and Southern
      Alberta Renal Programs, and clinical laboratories in Alberta. RESULTS: During a
      median follow-up of 4.1 years, 43,863 participants were hospitalized for heart
      failure; 6,274 participants, for hyperkalemia; 2,035 participants, for volume
      overload; and 481 participants, for malignant hypertension. All 4 conditions were
      more common at lower estimated glomerular filtration rates and in the presence of
      albuminuria. In the subset of participants with CKD, heart failure, hyperkalemia,
      and volume overload were associated most strongly with older age, diabetes,
      chronic liver disease, and prior heart failure. Malignant hypertension was
      associated with prior hypertension, aboriginal status, and peripheral vascular
      disease. Remote-dwelling participants were more likely to experience heart
      failure and malignant hypertension than those living closer to providers.
      LIMITATIONS: No data for medication use or potentially important process-based
      outcomes for study participants. CONCLUSIONS: Our findings suggest that future
      studies seeking to determine how to prevent ambulatory care-sensitive conditions
      in people with CKD should target remote dwellers and those with comorbid
      conditions such as concomitant heart failure and liver disease.

PMID- 24731740
TI  - Histopathologic effect of APOL1 risk alleles in PLA2R-associated membranous
      glomerulopathy.

PMID- 24731741
TI  - Congenital anomalies of the aortic arch in acute type-a aortic dissection:
      implications for monitoring, perfusion strategy, and surgical repair.
AB  - OBJECTIVE: To assess whether management of acute Stanford type-A aortic
      dissection differs in patients with congenital anomalies of the aortic arch
      compared with standard institutional practice. DESIGN: Retrospective analysis of
      all consecutive patients from 2001 through 2011. SETTING: Quaternary referral
      center for surgical management of thoracic aortic disease. PARTICIPANTS: All
      patients with arch anomalies who underwent surgery for acute Stanford type-A
      aortic dissection during the study period (n = 43). INTERVENTIONS: Surgical
      management, anesthetic monitoring, and perfusion strategy were analyzed in a
      retrospective fashion. No new interventions were undertaken as part of this
      study. MEASUREMENTS AND MAIN RESULTS: Management differed most in patients with
      an aberrant right subclavian artery (n = 5), because the institutional standard
      of right axillary artery cannulation with left upper extremity arterial pressure
      monitoring was not possible. In patients with one of two "bovine" arch patterns
      (n = 32), management differed in the conduct of selective antegrade cerebral
      perfusion, which could include clamping above or below the takeoff of the left
      common carotid artery (and, therefore, produced unilateral or bilateral antegrade
      cerebral perfusion). All patients with a connective tissue disorder exhibited a
      bovine arch pattern. Management of patients with a right arch (n = 3) reflected
      the opposite of management for normal anatomy (for patients with traditional
      mirror-image branching) or opposite that of the aberrant right subclavian group
      (for patients who had a corresponding aberrant left subclavian artery).
      CONCLUSIONS: Rational management reflected the anatomic variations observed.
      These results support the importance of interdisciplinary planning, especially in
      an emergency, to optimize outcome.

PMID- 24731743
TI  - Preoperative brain natriuretic peptide predicts late mortality and functional
      class but not hospital readmission after cardiac surgery.
AB  - OBJECTIVES: N-terminal brain natriuretic peptide (NT-proBNP) is an established
      biomarker of heart failure and has been found to predict mortality and morbidity
      after cardiac surgery. The aim of this study was to investigate whether
      preoperative NT-proBNP can predict postoperative New York Heart Association
      (NYHA) functional class and hospital readmission in addition to morbidity and
      mortality. DESIGN: Retrospective. SETTING: University hospital. PARTICIPANTS: All
      patients undergoing aortic valve replacement for aortic stenosis and coronary
      artery bypass grafting from January to December 2008 (n = 390). MEASUREMENTS AND
      MAIN RESULTS: Preoperative NT-proBNP was recorded prospectively. Five-year
      mortality was obtained through national registries. Postoperative functional
      class, morbidity, and hospital readmission were obtained through telephone
      interviews. Patients were divided into quartiles based on preoperative NT-proBNP;
      the medians of each quartile were 103 ng/L, 291 ng/L, 825 ng/L and 2,375 ng/L.
      Increased preoperative NT-proBNP was associated with reduced postoperative
      functional class. In the first quartile, 7% (7/97) were in NYHA functional class
      III-IV compared to 26% (25/97) in the fourth quartile (p<0.01). Increased
      preoperative NT-proBNP was also associated with reduced long-term survival
      (p<0.01). The covariate adjusted hazard ratio for mortality in the fourth
      quartile was 2.9 (1.61-5.08; p<0.01) compared to the other quartiles. No
      association was found between preoperative NT-proBNP and postoperative hospital
      readmission. CONCLUSIONS: Increased preoperative NT-proBNP is associated with
      reduced long-term survival and functional class but not hospital readmission post
      cardiac surgery. Thus, NT-proBNP might have additive value to established risk
      factors in the preoperative assessment of patients undergoing cardiac surgery.

PMID- 24731742
TI  - Early versus late initiation of renal replacement therapy in critically ill
      patients with acute kidney injury after cardiac surgery: a systematic review and
      meta-analysis.
AB  - OBJECTIVE: To investigate the impact of early versus late renal replacement
      therapy (RRT) on mortality in patients with acute kidney injury (AKI) after
      cardiac surgery. DESIGN: Meta-analysis of 9 retrospective cohort studies and 2
      randomized clinical trials extracted from the Medline engine from 1950 to 2013.
      SETTING: University medical school. PARTICIPANTS: 841 Patients. INTERVENTIONS:
      None. MEASUREMENTS AND MAIN RESULTS: A total of 841 patients were studied. Pooled
      estimates of the odds ratio with 95% confidence interval using a random-effect
      model were conducted as well as the heterogeneity, publication bias, and
      sensitivity analysis. Primary outcome was 28-day mortality, and secondary outcome
      was the intensive care unit (ICU) length of stay. The 28-days mortality rate was
      lower in the early RRT group (OR = 0.29, 95% CI, 0.16-0.52, p<0.0001, NNT = 5).
      Heterogeneity was high (I2 = 56%), and publication bias was low. Secondary
      outcome suggested 3.9 (1.5-6.3) days shorter ICU stay in the early RRT group,
      p<0.0001, with extremely high heterogeneity (I(2) = 99%), and low publication
      bias. Specifically, studies before 2000 and studies with mortality less than 50%
      in the late RRT group reported significantly higher odds ratio and mean
      difference than overall value favoring early RRT. CONCLUSION: Early initiation of
      RRT for patients with AKI after cardiac surgery revealed lower 28-days mortality
      and shorter ICU length of stay. However, this was based on 11 studies of various
      qualities with very high heterogeneity of results. Defining treatment guidelines
      needs further research with a larger and better database.

PMID- 24731744
TI  - Etiologies and early diagnosis of short stature and growth failure in children
      and adolescents.
AB  - Accurate measurement of height and weight using standardized techniques is a
      fundamental component of pediatric medical visits. Calculation of height velocity
      over time enables comparison with standardized growth charts to identify
      potential deviations from normal. Growth deviations may be expressed as SD from
      the normal population mean for children of comparable age and sex; children with
      heights >2 SD below the mean are generally classified as short stature. In a
      child with suspected impaired growth, a detailed evaluation should be conducted
      to identify the cause. Such an evaluation may include a combination of personal,
      family, and social history; physical examination; general and perhaps specialized
      laboratory evaluations; radiologic examinations; genetic testing; and
      consultation with a pediatric subspecialist, such as a pediatric endocrinologist.
      Variants of normal growth include familial short stature, constitutional delay of
      growth and puberty, and small for gestational age with catch-up growth.
      Pathological causes of abnormal growth include many systemic diseases and their
      treatments, growth hormone deficiency, and a series of genetic syndromes,
      including Noonan syndrome and Turner syndrome. Children with short stature in
      whom no specific cause is identified may be diagnosed with idiopathic short
      stature. Early identification of abnormal growth patterns and prompt referral to
      specialist care offer children with growth failure and/or short stature the
      greatest chance for appropriate diagnosis, treatment, and improved clinical
      outcomes. 

PMID- 24731746
TI  - Study of epileptic drop attacks in symptomatic epilepsy of early childhood -
      differences from those in myoclonic-astatic epilepsy.
AB  - OBJECTIVES: We studied epileptic drop attacks (EDA) in symptomatic epilepsy of
      early childhood by means of video-polygraphic recordings and compared clinico
      electrical differences in EDA among patients with idiopathic myoclonic-astatic
      epilepsy (MAE). SUBJECTS AND METHODS: Subjects consisted of 21 children with
      symptomatic epilepsy and 20 with idiopathic MAE whose EDA were documented at an
      age between 7 months and 6 years. The seizure types causing EDA as well as other
      demographic data were compared between the two epilepsy types. RESULTS: A video
      polygraphic study captured a total of 188 EDA (median: 8) in patients with
      symptomatic epilepsy and 182 EDA (median: 7) in those with idiopathic MAE. In the
      former, EDA were caused by epileptic spasms (ES) corresponding to generalized
      biphasic slow discharges, sharp-and-slow wave complexes, or the flattening of
      ongoing background activity in 15 patients, atonic seizures associated with runs
      of generalized spike-and-wave complexes in four patients, and myoclonic-atonic
      seizures in the remaining two patients. The mode of occurrence of EDA in ES was
      periodic clustering in eight of 15 patients. Interictal EEG revealed generalized
      irregular multiple spikes-and-waves with focal or multifocal accentuations.
      Sixteen idiopathic MAE patients had myoclonic-atonic seizures while the remaining
      four had myoclonic-flexor seizures, all corresponding to generalized high
      amplitude spikes or polyspike-and-wave complexes and occurring singly.
      CONCLUSION: EDA often seen in young children with symptomatic epilepsy were most
      frequently caused by flexor type ES and rarely by myoclonic-atonic seizures, a
      hallmark seizure type of MAE. In a clinical setting, the occurrence of periodic
      clusters and independent focal or multifocal accentuations of generalized spike
      and-wave complexes in interictal EEG may indicate EDA caused by ES.

PMID- 24731745
TI  - Assessment of pharmacokinetic changes of meropenem during therapy in septic
      critically ill patients.
AB  - BACKGROUND: Meropenem is a carbapenem antibiotic commonly used in critically ill
      patients to treat severe infections. The available pharmacokinetic (PK) data has
      been mostly obtained from healthy volunteers as well as from clinical studies
      addressing selected populations, often excluding the elderly and also patients
      with renal failure. Our aim was to study PK of meropenem in a broader population
      of septic critically ill patients. METHODS: We characterized the PK of meropenem
      in 15 critically ill patients during the first 36 hrs of therapy. Aditionally,
      whenever possible, we collected a second set of late plasma samples after 5 days
      of therapy to evaluate PK intra-patient variability and its correlation with
      clinical course.Patients received meropenem (1 g every 8 hrs IV). Drug plasma
      profiles were determined by high-performance liquid chromatography. The PK of
      meropenem was characterized and compared with clinical parameters. RESULTS:
      Fifteen septic critically ill patients (8 male, median age 73 yrs) were included.
      The geometric mean of the volume of distribution at the steady state (Vss)/weight
      was 0.20 (0.15-0.27) L/kg. No correlation of Vss/weight with severity or
      comorbidity scores was found. However the Sequential Organ Failure Assessment
      score correlated with the Vss/weight of the peripheral compartment (r2 = 0.55, p
      = 0.021). The median meropenem clearance (Cl) was 73.3 (45-120) mL/min correlated
      with the creatinine (Cr) Cl (r2 = 0.35, p = 0.033).After 5 days (N = 7) although
      Vss remained stable, a decrease in the proportion of the peripheral compartment
      (Vss2) was found, from 61.3 (42.5-88.5)% to 51.7 (36.6-73.1)%. No drug
      accumulation was noted. CONCLUSIONS: In this cohort of septic, unselected,
      critically ill patients, large meropenem PK heterogeneity was noted, although
      neither underdosing nor accumulation was found. However, Cr Cl correlated to
      meropenem Cl and the Vss2 decreased with patient's improvement.

PMID- 24731747
TI  - [Is it wise to continue using phosphate enemas?].

PMID- 24731748
TI  - High class II-associated invariant chain peptide expression on residual leukemic
      cells is associated with increased relapse risk in acute myeloid leukemia.
AB  - The presence of class II-associated invariant chain (CLIP) on leukemic cells is
      negatively associated with clinical outcome in untreated acute myeloid leukemia
      (AML). CLIP plays a role in the immune escape of leukemic cells, suggesting that
      it impairs the immunogenicity of minimal residual disease (MRD) cells causing a
      relapse. Here, we demonstrate that CLIP expression on leukemia-associated
      phenotype (LAP)-positive cells during follow-up is significantly correlated with
      a shortened relapse-free survival, even in those patients who are generally
      considered as MRD(low) (0.01-0.1% LAP(+) cells). Consequently, CLIP evaluation
      could be of additional value in the evaluation of MRD to predict a relapse of
      AML. 

PMID- 24731749
TI  - Nerve growth factor in the adult brain of a teleostean model for aging research:
      Nothobranchius furzeri.
AB  - Nerve growth factor (NGF) acts on central nervous system neurons, regulating
      naturally occurring cell death, synaptic connectivity, fiber guidance and
      dendritic morphology. The dynamically regulated production of NGF beginning in
      development, extends throughout adult life and aging, exerting numerous roles
      through a surprising variety of neurons and glial cells. This study analyzes the
      localization of NGF in the brain of the teleost fish Nothobranchius furzeri, an
      emerging model for aging research due to its short lifespan. Immunochemical and
      immunohistochemical experiments were performed by employing an antibody mapping
      at the N-terminus of the mature chain human origin NGF. Western blot analysis
      revealed an intense and well defined band of 20 kDa, which corresponds to proNGF
      of N. furzeri. Immunohistochemistry revealed NGF immunoreactivity (IR) diffused
      throughout all regions of telencephalon, diencephalon, mesencephalon and
      rhomboencephalon. It was detected in neurons and in glial cells, the latter
      mostly lining the mesencephalic and rhomboencephalic ventricles. Particularly in
      neurons, NGF IR was localized in perikarya and, to a less extent, in fibers. The
      widespread distribution of proNGF suggests that it might modulate numerous
      physiological functions in the adult brain of N. furzeri. The present survey
      constitutes a baseline study to enhance the understanding of the mechanisms
      underlying the role of NGF during aging processes.

PMID- 24731750
TI  - Chronic non-bloody diarrhoea: a prospective study in Malmo, Sweden, with focus on
      microscopic colitis.
AB  - BACKGROUND: Chronic non-bloody diarrhoea affects up to 5% of the population.
      Microscopic colitis is one of the most common causes, encompassing the subtypes
      collagenous colitis and lymphocytic colitis. The diagnosis of microscopic colitis
      is made by histological examination of colonic mucosal biopsy specimens. The aim
      of this investigation was to determine whether laboratory parameters or questions
      about disease history or concomitant disease could be helpful in discriminating
      patients with MC from those with a histologically normal colonic mucosa.
      FINDINGS: Patients admitted for colonoscopy because of chronic non-bloody
      diarrhoea (>2 loose stools for >3 weeks) at endoscopy units in Malmo during 2007
      and 2009, were enrolled. A total number of 78 patients were included (60 women,
      18 men, median age 59, IQR 45-69 years). Out of these 78, 15 patients (19%) had
      microscopic colitis (CC; n = 10, LC; n = 5). MC was especially prevalent in
      patients above the age of 50 (25%). No differences were found between those with
      normal histology and MC in laboratory analyses (inflammatory and liver
      parameters). Neither were differences shown in questions regarding symptoms,
      environmental factors or concomitant diseases except for an association with
      celiac disease (p = 0.019) and a trend maybe indicating an inverse association
      with appendectomy (p = 0.057). CONCLUSIONS: Microscopic colitis is associated
      with female gender, celiac disease and consumption of NSAIDs. Trends were
      observed indicating that age above 50 years, acute onset and absence of
      appendectomy may be associated with MC. No associations were observed with other
      symptoms, calprotectin levels or liver parameters.

PMID- 24731751
TI  - Modern contraceptive utilization among female ART attendees in health facilities
      of Gimbie town, West Ethiopia.
AB  - BACKGROUND: In many areas of the world where HIV prevalence is high, rates of
      unintended pregnancy have also been shown to be high. Of all pregnancies
      worldwide in 2008, 41% were reported as unintended and approximately 50% of these
      ended in abortion. To address these problems family planning is the best
      solution. Therefore, the purpose of the study was to assess modern contraceptive
      use among females on ART in health facilities of Gimbie town, Western Ethiopia.
      METHODS: A facility based cross-sectional study was conducted in Gimbie town,
      western Ethiopia from December 2012 to January 2013. HIV infected women of
      reproductive age group (15-49 years) who came for ART care follow up during the
      data collection period were included in the study. Data was collected using an
      interviewer administered questionnaire. Binary logistic regression and
      multivariate analysis were employed using SPSS version 17. RESULTS: Three hundred
      ninety five women on ART have participated in the study. More than half, 224
      (56.7%), of the respondents were using modern contraceptive, of whom 67 (30%) use
      dual contraceptive method. Having information on modern contraception is
      positively associated with modern contraceptive use with (AOR=6.3, 95% CI (1.67,
      24.1)) and respondents who have family size <=4 were 50% less contraceptive users
      than those who have family size >4 (AOR=0.51, 95% CI (0.27, 0.96)). CONCLUSION:
      In this study contraceptive use among HIV positive women is better than the
      general population. However, use of dual methods, long acting and permanent
      method of contraceptives were found to be low. Continuous and targeted
      information provision on modern contraceptive should be done.

PMID- 24731752
TI  - Transcranial direct current stimulation of the frontal-parietal-temporal area
      attenuates smoking behavior.
AB  - Many brain regions are involved in smoking addiction (e.g. insula, ventral
      tegmental area, prefrontal cortex and hippocampus), and the manipulation of the
      activity of these brain regions can show a modification of smoking behavior. Low
      current transcranial direct current stimulation (tDCS) is a noninvasive way to
      manipulate cortical excitability, and thus brain function and associated
      behaviors. In this study, we examined the effects of inhibiting the frontal
      parietal-temporal association area (FPT) on attention bias to smoking-related
      cues and smoking behavior in tobacco users. This inhibition is induced by
      cathodal tDCS stimulation. We tested three stimulation conditions: 1) bilateral
      cathodal over both sides of FPT; 2) cathodal over right FPT; and 3) sham-tDCS.
      Visual attention bias to smoking-related cues was evaluated using an eye tracking
      system. The measurement for smoking behavior was the number of daily cigarettes
      consumed before and after tDCS treatment. We found that, after bilateral cathodal
      stimulation of the FPT area, while the attention to smoking-related cues showed a
      decreased trend, the effects were not significantly different from sham
      stimulation. The daily cigarette consumption was reduced to a significant level.
      These effects were not seen under single cathodal tDCS or sham-tDCS. Our results
      show that low current tDCS of FPT area attenuates smoking cue-related attention
      and smoking behavior. This non-invasive brain stimulation technique, targeted at
      FPT areas, might be a promising method for treating smoking behavior. 

PMID- 24731753
TI  - T cells infiltrate the liver and kill hepatocytes in HLA-B(*)57:01-associated
      floxacillin-induced liver injury.
AB  - Drug-induced liver injury is a major safety issue. It can cause severe disease
      and is a common cause of the withdrawal of drugs from the pharmaceutical market.
      Recent studies have identified the HLA-B(*)57:01 allele as a risk factor for
      floxacillin (FLUX)-induced liver injury and have suggested a role for cytotoxic
      CD8(+) T cells in the pathomechanism of liver injury caused by FLUX. This study
      aimed to confirm the importance of FLUX-reacting cytotoxic lymphocytes in the
      pathomechanism of liver injury and to dissect the involved mechanisms of
      cytotoxicity. IHC staining of a liver biopsy from a patient with FLUX-induced
      liver injury revealed periportal inflammation and the infiltration of cytotoxic
      CD3(+) CD8(+) lymphocytes into the liver. The infiltration of cytotoxic
      lymphocytes into the liver of a patient with FLUX-induced liver injury
      demonstrates the importance of FLUX-reacting T cells in the underlying
      pathomechanism. Cytotoxicity of FLUX-reacting T cells from 10 HLA-B(*)57:01(+)
      healthy donors toward autologous target cells and HLA-B(*)57:01-transduced
      hepatocytes was analyzed in vitro. Cytotoxicity of FLUX-reacting T cells was
      concentration dependent and required concentrations in the range of peak serum
      levels after FLUX administration. Killing of target cells was mediated by
      different cytotoxic mechanisms. Our findings emphasize the role of the adaptive
      immune system and especially of activated drug-reacting T cells in human
      leukocyte antigen-associated, drug-induced liver injury.

PMID- 24731756
TI  - Should sleep laboratories have their own predictive formulas for continuous
      positive airway pressure for patients with obstructive sleep apnea syndrome?
AB  - BACKGROUND: Several formulas predicting optimal continuous positive airway
      pressure (CPAP) for obstructive sleep apnea treatment have been developed and
      diverse parameters selected as predictive factors in different sleep laboratories
      using different ethnic groups. This study aimed to validate a constructed
      predictive formula for the study laboratory and to test the hypothesis that sleep
      laboratories should have their own predictive formulas. METHODS: Fifty-seven
      adult subjects with obstructive sleep apnea syndrome (OSAS) were enrolled in the
      model-building set and underwent two polysomnography (PSG) studies to diagnose
      OSAS and titrate for optimal CPAP. A predictive formula, derived from
      anthropometric and polysomnographic variables, was validated together with two
      other predictive formulas in 30 subjects by comparing the mean predictive CPAP
      values, rates of successful prediction, and agreements. RESULTS: Regression
      analysis showed that apnea-hypopnea index (AHI), SaO2nadir (nadir of arterial
      oxyhemoglobin saturation by pulse oximetry), and body mass index (BMI) strongly
      correlated with optimal CPAP. The derived predictive formula for the study
      laboratory was: CPAPpred (predictive CPAP) = 6.380 + 0.033 * AHI - 0.068 *
      SaO2nadir + 0.171 * BMI (R(2) = 0.335, adjusted R(2) = 0.298). In Taiwan,
      different predictive formulas used by different sleep laboratories with different
      independent predictors led to similar mean predictive CPAP values to the mean
      observed optimal CPAP values, rates of successful prediction, and agreements with
      the observed optimal CPAP. There were significant differences between the mean
      predictive CPAP values and mean observed optimal CPAP values, lower rates of
      successful prediction, and negatively skewed 95% confidence interval (CI) when
      using a predictive formula derived from different ethnic populations. CONCLUSION:
      A sleep laboratory may not need to have its own predictive formula for
      determining the optimal effective CPAP but should adopt the one derived from the
      same ethnicity of OSAS patients as the reference formula.

PMID- 24731754
TI  - Streptozotocin-induced diabetes prolongs twitch duration without affecting the
      energetics of isolated ventricular trabeculae.
AB  - BACKGROUND: Diabetes induces numerous electrical, ionic and biochemical defects
      in the heart. A general feature of diabetic myocardium is its low rate of
      activity, commonly characterised by prolonged twitch duration. This diabetes
      induced mechanical change, however, seems to have no effect on contractile
      performance (i.e., force production) at the tissue level. Hence, we hypothesise
      that diabetes has no effect on either myocardial work output or heat production
      and, consequently, the dependence of myocardial efficiency on afterload of
      diabetic tissue is the same as that of healthy tissue. METHODS: We used isolated
      left ventricular trabeculae (streptozotocin-induced diabetes versus control) as
      our experimental tissue preparations. We measured a number of indices of
      mechanical (stress production, twitch duration, extent of shortening, shortening
      velocity, shortening power, stiffness, and work output) and energetic (heat
      production, change of enthalpy, and efficiency) performance. We calculated
      efficiency as the ratio of work output to change of enthalpy (the sum of work and
      heat). RESULTS: Consistent with literature results, we showed that peak twitch
      stress of diabetic tissue was normal despite suffering prolonged duration. We
      report, for the first time, the effect of diabetes on mechanoenergetic
      performance. We found that the indices of performance listed above were
      unaffected by diabetes. Hence, since neither work output nor change of enthalpy
      was affected, the efficiency-afterload relation of diabetic tissue was
      unaffected, as hypothesised. CONCLUSIONS: Diabetes prolongs twitch duration
      without having an effect on work output or heat production, and hence efficiency,
      of isolated ventricular trabeculae. Collectively, our results, arising from
      isolated trabeculae, reconcile the discrepancy between the mechanical performance
      of the whole heart and its tissues.

PMID- 24731755
TI  - Prognosis of concomitant users of clopidogrel and proton-pump inhibitors in a
      high-risk population for upper gastrointestinal bleeding.
AB  - BACKGROUND: It is unclear whether concomitant use of clopidogrel and proton-pump
      inhibitors (PPIs) increases the risk of recurrence of cardiovascular disease or
      death in patients at high risk of upper gastrointestinal (GI) bleeding. METHODS:
      Based on the Swedish Patient Register, a cohort of cardiovascular disease
      (including acute myocardial infarction, stroke and angina, from 2006 to 2008) was
      selected from a population with any diagnosis of upper GI bleeding. Data on drug
      prescription was retrieved from the Prescribed Drug Register. Patients entered
      into the cohort after their first discharge for cardiovascular disease and were
      followed up to death, recurrence of cardiovascular disease, or 90 days. A Cox
      regression model was conducted and hazard ratios (HRs) with 95% confidence
      intervals (CIs) were estimated to evaluate the risks among users of different
      drug prescriptions. RESULTS: Patients who were current users of only PPIs (HR
      2.02, 95% CI 1.19-3.44), only clopidogrel (HR 1.14, 95% CI 0.53-2.45) and
      nonusers of both (HR 2.36, 95% CI 1.39-4.00) were at a higher risk of death
      compared with patients with a concomitant use. Results were similar among 1779
      patients who had any history of upper GI bleeding (HR 2.05, 95% CI 1.18-3.54; HR
      1.25, 95% CI 0.57-2.72; HR 2.30, 95% CI 1.33-3.98, respectively). CONCLUSION:
      Among patients at high risk of upper GI bleeding, those with a concomitant use of
      PPIs and clopidogrel were at a decreased risk of mortality, and possibly also a
      decreased risk of recurrence of cardiovascular disease.

PMID- 24731757
TI  - Molecular typing and characterization of TEM, SHV, CTX-M, and CMY-2 beta
      lactamases in Enterobacter cloacae strains isolated in patients and their
      hospital environment in the west of Algeria.
AB  - OBJECTIVES: Enterobacter cloacae is a major nosocomial bacterium causing severe
      infections. A multicenter retrospective cohort study was conducted to collect
      baseline information on the molecular characteristics of beta-lactamase producing
      Enterobacter cloacae in the west of Algeria. MATERIALS AND METHODS: We report a
      series of 42 extended-spectrum beta-lactamase (ESBL) producing non-repetitive
      Enterobacter cloacae strains, collected in 3 university hospital (Tlemcen, Oran,
      and Sidi Bel Abbes). Antibiotic susceptibility testing (antibiogram and MIC) and
      screening for ESBL were performed according to the French Society for
      Microbiology guidelines. PFGE typing was used to characterize the clonality of
      all the strains. beta-lactamase genes (blaTEM, blaSHV, blaCTX-M, blaECB, and
      blaCMY-2) were amplified by PCR with specific primers. Plasmid isolation,
      electroporation, and conjugation experiments were carried out using standard
      methods. RESULTS: Sequence analysis revealed that most strains produced CTX-M
      type ESBLs (CTX-M-15 and CTX-M-3), whereas only 5 produced SHV-type ESBLs (SHV
      12). The blaTEM gene was identified in all strains of Enterobacter cloacae.
      Several epidemic clones were determined. One strain was found to produce plasmid
      mediated AmpC beta-lactamase (CMY-2); this gene was transferred from E. cloacae
      by electroporation. Conjugation experiments showed that blaCTX-M, blaTEM, and
      blaSHV were carried by conjugative plasmids of high molecular weight (>=70kb).
      CONCLUSION: The emergence of resistance genes is a public health problem.

PMID- 24731758
TI  - Retraining function in people with Parkinson's disease using the Microsoft
      kinect: game design and pilot testing.
AB  - BACKGROUND: Computer based gaming systems, such as the Microsoft Kinect (Kinect),
      can facilitate complex task practice, enhance sensory feedback and action
      observation in novel, relevant and motivating modes of exercise which can be
      difficult to achieve with standard physiotherapy for people with Parkinson's
      disease (PD). However, there is a current need for safe, feasible and effective
      exercise games that are appropriate for PD rehabilitation. The aims of this study
      were to i) develop a computer game to rehabilitate dynamic postural control for
      people with PD using the Kinect; and ii) pilot test the game's safety and
      feasibility in a group of people with PD. METHODS: A rehabilitation game aimed at
      training dynamic postural control was developed through an iterative process with
      input from a design workshop of people with PD. The game trains dynamic postural
      control through multi-directional reaching and stepping tasks, with increasing
      complexity across 12 levels of difficulty. Nine people with PD pilot tested the
      game for one session. Participant feedback to identify issues relating to safety
      and feasibility were collected using semi-structured interviews. RESULTS:
      Participants reported that they felt safe whilst playing the game. In addition,
      there were no adverse events whilst playing. In general, the participants stated
      that they enjoyed the game and seven of the nine participants said they could
      imagine themselves using the game at home, especially if they felt it would
      improve their balance. The Flow State Scale indicated participants were immersed
      in the gameplay and enjoyed the experience. However, some participants reported
      that they found it difficult to discriminate between different types and
      orientations of visual objects in the game and some also had difficulty with the
      stepping tasks, especially when performed at the same time as the reaching tasks.
      CONCLUSION: Computer-based rehabilitation games using the Kinect are safe and
      feasible for people with PD although intervention trials are needed to test their
      safety, feasibility and efficacy in the home.

PMID- 24731759
TI  - Fat embolism syndrome after nailing an isolated open tibial fracture in a stable
      patient: a case report.
AB  - BACKGROUND: Fat embolism syndrome is a potentially fatal complication of long
      bone fractures. It is usually seen in the context of polytrauma or a femoral
      fracture. There are few reports of fat embolism syndrome occurring after isolated
      long bone fractures other than those of the femur. CASE PRESENTATION: We describe
      a case of fat embolism syndrome in a 33-year-old Caucasian man. He was being seen
      for an isolated Gustilo's grade II open tibial fracture. He was deemed clinically
      stable, so we proceeded to treat the fracture with intramedullary reamed nailing.
      He developed fat embolism syndrome intraoperatively and was treated successfully.
      CONCLUSION: This case caused us to question the use of injury severity scoring
      for isolated long bone fractures. It suggests that parameters that have been
      described in the literature other than that the patient is apparently clinically
      stable should be used to establish the best time for nailing a long bone
      fracture, thereby improving patient safety.

PMID- 24731760
TI  - Older opposite-sex romantic partners, sexual risk, and victimization in
      adolescence.
AB  - This study examined how age gaps among opposite-sex romantic partners related to
      sexual risk-taking and victimization by partners among 201 at-risk adolescents
      (60.2% female). We examined three questions: (a) is younger partner age, age gap
      between partners, or a combination of these two factors most strongly related to
      negative outcomes; (b) do age gaps relate to negative outcomes differently for
      male versus female adolescents; and (c) why do age gaps relate to negative
      outcomes? Results revealed that the wider the age gap between partners, the more
      likely adolescents were to engage in sex and the less likely they were to use
      protection against pregnancy and STIs. Wider age gaps were also associated with
      more frequent emotional and physical victimization and higher odds of unwanted
      sexual behavior. Findings did not differ significantly by gender or younger
      partner age. Analyses revealed that the wider the age gap, the more likely both
      partners were to engage in risky lifestyles (i.e., substance use and
      delinquency), and risky lifestyles - rather than poor negotiation or decision
      making equality - helped to explain associations between age gaps and engagement
      in sexual intercourse and victimization experiences. Results suggest that
      relationships with age gaps tend to involve two partners who are engaging in
      deviant lifestyles overall, further corroborating the need to identify and
      provide services to these youth. Results also support movements toward
      considering partner age gaps rather than relying on a set age of consent when
      determining adolescents' legal competency to consent to sex. 

PMID- 24731761
TI  - Buddhism and children: scholars struggle with the story of the Buddha's son.

PMID- 24731762
TI  - A commercially available multiplex real-time PCR for detection of pathogens in
      cardiac valves from patients with infective endocarditis.
AB  - Infective endocarditis (IE) is a life-threatening condition, burdened by high
      mortality. Current guidelines recommend that, in case of negative culture result,
      tissues from excised heart valves or vegetations from patients with suspected IE
      should be referred for broad-range bacterial PCR and sequencing. In this proof-of
      concept study, the diagnostic utility of the commercially available multiplex
      real-time PCR system SeptiFast (SF), performed on cardiac valves, was evaluated
      in a selected population of 20 patients with definite IE of known origin, in
      comparison with culture. A significant difference was found between SF and
      culture in the rate of pathogen detection (19 versus 3 respectively; chi-square
      14.06; P=0.0002). SF sensitivity was 95%; specificity, 100%; positive predictive
      value (PPV), 100%; and negative predictive value (NPV), 83.3%. Culture
      sensitivity was 15%; specificity, 100%; PPV, 100%; and NPV, 22.7%. SF assay,
      performed on culture-negative excised heart valves, can be useful for the
      etiological diagnosis of IE. 

PMID- 24731763
TI  - A Chinese 2-herb formula (NF3) promotes hindlimb ischemia-induced
      neovascularization and wound healing of diabetic rats.
AB  - Diabetic foot ulcer is closely associated with peripheral vascular disease.
      Enhancement of tissue oxidative stress, reduction of nitric oxide (NO) and
      angiogenic growth factors, and abnormal matrix metalloproteinase (MMP) activity
      are pathophysiological factors in post-ischemic neovascularization and diabetic
      wound healing. Our previous study demonstrated that the Chinese 2-herb formula,
      NF3, showed significant wound healing effects on diabetic foot ulcer rats. A
      novel rat diabetic foot ulcer with hindlimb ischemia model was established in
      order to strengthen our claims on the diabetic wound healing and post-ischemic
      neovascularization effects of NF3. Our results demonstrate that NF3 can
      significantly reduce the wound area of the diabetic foot ulcer rat with hindlimb
      ischemia by 21.6% (p<0.05) compared with the control group. In addition, flow
      cytometric analysis revealed that NF3 could boost circulating EPC levels for
      local wound vessel incorporation. Immunohistochemical analysis showed that NF3
      could significantly augment blood vessel density, VEGF and eNOS expression, and
      attenuate tissue oxidative stress of ischemic muscles (p<0.001). NF3
      significantly stimulated MMP activity involved in angiogenesis. Our study shows,
      for the first time, the beneficial effects of NF3 in wound healing and post
      ischemic neovascularization in diabetes.

PMID- 24731764
TI  - Disparities in trauma: the impact of socioeconomic factors on outcomes following
      traumatic hollow viscus injury.
AB  - BACKGROUND: This piece aims to examine the relationships between hollow viscus
      injury (HVI) and socioeconomic factors in determining outcomes. HVI has well
      defined injury patterns with complex postoperative convalescence and morbidity,
      representing an ideal focus for identifying potential disparities among a
      homogeneous injury population. MATERIALS AND METHODS: A retrospective review
      included patients admitted to a level I trauma center with HVI from 2000-2009, as
      identified in the Trauma Registry of the American College of Surgeons. Patients
      with concomitant significant solid organ or vasculature injury were excluded. US
      Census (2000) median household income by zip code was used as socioeconomic
      proxy. Demographic and injury-related variables were also included. Endpoints
      were mortality and outcomes associated with HVI morbidity. RESULTS: A total of
      933 patients with HVI were identified and 256 met inclusion criteria. There were
      23 deaths (9.0%), and mortality was not associated with race, gender, income, or
      payer source. However, lower median household income was significantly associated
      with longer intervals to ostomy takedown (P = 0.032). Additionally, private
      payers had significantly lower rates of anastomotic leak (0% [0/73] versus 7.1%
      [13/183], P = 0.019) and fascial dehiscence (5.5% [4/73] versus 16.9% [31/183], P
      = 0.016), while self-payers had significantly higher rates of abscess formation,
      both overall (24% [24/100] versus 10.2% [16/156], P = 0.004) and among
      penetrating injuries (27.4% [23/84] versus 13.6% [12/88], P = 0.036).
      CONCLUSIONS: Socioeconomic status may not impact overall mortality among trauma
      patients with hollow viscus injuries, but private insurance appears to be
      protective of morbidity related to anastomotic leak, fascial dehiscence, and
      abscess formation. This supports that socioeconomic disparity may exist within
      long-term outcomes, particularly regarding payer source.

PMID- 24731765
TI  - Organ donation from burn-injured patients--a national perspective.
AB  - BACKGROUND: There is a discrepancy between publically available data from the
      United Network for Organ Sharing (UNOS) database and perception of the incidence
      of mortally burn-injured patients serving as organ donors. In the last 5 y, a
      single burn center referred several patients who went on to successfully donate
      multiple organs. However, UNOS data indicate very few referrals of patients with
      burn injuries nationwide. This discrepancy in UNOS-reported occurrences versus
      institutional experience prompted this work. METHODS: UNOS data from 1988-2012
      was examined for causes of death related to thermal injury, electrical injury,
      inhalation injury, or carbon monoxide poisoning. The National Burn Repository was
      examined for burn center death rates and patient characteristics of those with
      reported nonsurvivable burn injuries. Finally, a national survey queried the
      clinical experiences and educated opinions of burn center directors, transplant
      surgeons, and organ procurement organization (OPO) representatives regarding
      organ donation in the burn-injured population. RESULTS: Between 42% and 52% of
      those surveyed responded. Survey data indicate that at least 61 patients with
      burn-related injuries have served as organ donors in the past 5 y alone, versus
      23 identified in 24 y of UNOS data. Survey data also indicate that inhalation
      injuries were the most common burn-related injuries seen before successful organ
      procurement. Kidneys were the most commonly donated organs, but all major organs
      and tissues were represented in the experiences of surgeon and organ procurement
      organization respondents. Up to 10% surgeon respondents believe that patients
      with burn injuries should not be referred for possible organ donation.
      CONCLUSIONS: There are more organs donated by patients with mortal burn injuries
      than currently available UNOS data would suggest. Survey data suggest that these
      patients should be able to contribute successfully to the supply of organs needed
      by those on transplant waiting lists, but remain inconsistently recognized as
      such a resource. Knowledge about long-term organ and tissue viability from burn
      injured patients is lacking, and should be the focus of future research.

PMID- 24731766
TI  - Morphology and ultrastructure of the germarium in panoistic ovarioles of a basal
      "apterygotous" insect, Thermobia domestica.
AB  - It has been shown that in Drosophila the germline stem cells (GSCs), similar to
      the germline and non-germline stem cells of other species, develop and function
      in specialized microenvironments formed by somatic cells, referred to as the
      niches. In the fruit fly ovaries, the female GSCs divide asymmetrically to
      produce new GSCs and the progenitor cells, the cystoblasts (Cbs). Each Cb then
      divides to generate the cyst composed of 16 interconnected sibling cells, the
      cystocytes. After cyst formation, specific molecules are transferred to one of
      the cystocytes which differentiates into the oocyte, whereas the other 15
      cystocytes become the nurse cells. We have studied morphology and ultrastructure
      of the germaria in the ovarioles (ovaries) of a basal "apterygotous" insect, the
      firebrat (Thermobia domestica). Our analyses have revealed that in this insect,
      putative GSCs are present along the anterior apex of the germarium. These cells
      are separated from each other and from the basement lamina covering the ovariole
      by characteristic somatic cells, termed the apical somatic cells (ASCs), or their
      elongated processes. We believe that all the ASCs of a given ovariole constitute
      a "dispersed" niche in which putative GSCs are anchored. Our analyses have
      additionally shown that in Thermobia, both the Cbs and young (meiotic) oocytes
      are always individual and never form syncytial cysts. These findings indicate
      that in certain basal insects the syncytial phase of oogenesis has been
      eliminated during evolution. Finally, we show that in the early meiotic oocytes
      of Thermobia, during the so-called bouquet stage, prominent Balbiani bodies (Bbs)
      are formed. Analysis of serial micrographs indicates that the Bbs invariably
      arise next to the segment of the nuclear envelope to which the telomeres of the
      bouquet chromosomes are attached. We suggest, in the light of these data, that
      the localization of the Bb together with the polar attachment of the bouquet
      chromosomes play a crucial role in the early asymmetrization of Thermobia
      oocytes. 

PMID- 24731767
TI  - A region-based two-step P300-based brain-computer interface for patients with
      amyotrophic lateral sclerosis.
AB  - OBJECTIVE: The P300-based brain-computer interface (BCI) is designed to help
      patients with motor disabilities to control their environment, and it has been
      used successfully in patients with amyotrophic lateral sclerosis (ALS). However,
      some ALS patients were unable to use the visual P300-BCI with the conventional
      row/column presentation. In this study, we evaluated the effect of a newly
      developed region-based two-step P300 speller, which has a larger flashing area
      than the conventional visual array. METHODS: Seven ALS patients and seven age-
      and sex-matched able-bodied control subjects were required to input hiragana
      characters using our P300 BCI system. We prepared two types of input procedures,
      the conventional row/column (RC) speller and the two-step speller, and evaluated
      their online performance. RESULTS: The mean online accuracy of the ALS patients
      was 24% for the RC condition and 55% for the two-step condition. The accuracy of
      the control subjects was 71% and 83% for the RC and two-step condition,
      respectively. Accuracy in ALS patients was significantly lower than that in the
      control subjects, and the new visual stimuli significantly increased accuracy of
      ALS patients. Using the new speller, two ALS patients showed an initial accuracy
      sufficient for practical use (>70%). The other two ALS patients, who performed
      better in the first trial using the new speller, continued to experience the BCI
      system, and their mean accuracy increased to 92%. CONCLUSIONS: The two-step
      procedure for the visual P300 BCI system provided significantly increased
      accuracy for ALS patients compared with a conventional RC speller. SIGNIFICANCE:
      The new region-based two-step P300 speller was effective in ALS patients, and the
      system may be beneficial to expand their range of activities.

PMID- 24731768
TI  - Implications of cytokine genes in allergic asthma.
AB  - Asthma is a complex disease involving numerous mediator molecules and effector
      cells, in combination with a range of environmental determining factors.
      Cytokines play a key role in the physiopathological mechanisms of asthma; the
      study of the structure, regulation and variations of the genes that encode for
      these molecules is therefore crucial. Cytokines have extremely diverse roles, and
      exert effects both as activators and inhibitors of the innate and adaptive immune
      response. Certain modifications in the expression or structure of these
      molecules, resulting from the presence of polymorphisms, may give rise to
      deregulation of the mentioned effects, and therefore to a predisposition to
      develop concrete asthma phenotypes. 

PMID- 24731769
TI  - Indicators for childhood asthma in Spain, using the Rand method.
AB  - OBJECTIVE: To develop quality indicators to measure asthma care in primary health
      care. METHOD: A modified RAND was used, which included the systematic review of
      the literature in Embase, Cochrane and Pubmed Quality Agencies and Database. The
      work group identified the indicators, translated them into Spanish and resolved
      any duplicates. Each indicator is composed of several dimensions (access to care,
      clinical effectiveness, patient-centred quality and patient safety). A
      multidisciplinary panel of 98 professionals from all over Spain were invited to
      score each indicator using a Likert scale. After calculating the average and
      median of each indicator, this information was sent to those who responded (n=38)
      for a second round and further scoring. The agreement percentage for the group
      was obtained for each indicator. RESULTS: Of the 105 asthma indicators reviewed,
      we selected 46 that were presented to the panel of experts. In both Delphi
      phases, 37.1% of the members of the initial panel of experts responded. Of these,
      26 were primary care paediatricians, six were pulmonologists, three were nurses,
      two were pharmacists and one was an allergist. For 32 indicators, agreement
      exceeded 70% and seven of those scored highest for the various care aspects for
      asthmatic children. CONCLUSION: Quality indicators are presented for the follow
      up of asthma and their implementation in primary care, which have undergone a
      strict selection and agreement process by a multidisciplinary work group.

PMID- 24731770
TI  - DRESS syndrome induced by meropenem.

PMID- 24731771
TI  - Long-term efficacy of omalizumab in seven patients with treatment-resistant
      chronic spontaneous urticaria.
AB  - BACKGROUND: Monoclonal anti-IgE antibody omalizumab is a promising therapeutic
      option in patients with chronic urticaria (CU) resistant to non-sedating H1
      antihistamines (nsAH). However, data about its long-term efficacy and safety are
      still scant. OBJECTIVE: We retrospectively analysed the clinical course of
      patients with severe recalcitrant CU that were treated in our department with
      omalizumab for a period greater than 24 months. METHODS AND PATIENTS: Seven
      patients (six females, median 43 years) treated for a median of 35 months have
      been evaluated. Before treatment, all suffered from persistent symptoms despite
      receiving high doses of nsAH [4*/day], leukotriene antagonists and prednisolone
      (10-30 mg/day for a median duration of 48 months). Response to treatment was
      assessed using urticaria activity score (UAS) and a combined symptom/medication
      score. RESULTS: There was a complete remission of disease in four patients after
      the first dose of omalizumab. Before the 5th administration, all patients had a
      UAS of 0. We found a significant improvement in UAS between pre-treatment and
      first dose (p=0.017) and a gradual decrease in the symptom/medication score over
      the course of the first five administrations. Tapering of prednisolone was
      possible in all patients. Administration intervals were gradually increased,
      although all experienced resurgence of symptoms in cycles greater than six weeks.
      There were no reported adverse reactions attributable to the drug. CONCLUSION:
      Omalizumab was a safe and effective corticosteroid alternative for maintaining
      long-term remission of symptoms in these patients. Treatment intervals required
      individual patient-by-patient determination. The drug did not seem to alter the
      natural history of the disease.

PMID- 24731772
TI  - Atherogenic, fibrotic and glucose utilising actions of glucokinase activators on
      vascular endothelium and smooth muscle.
AB  - BACKGROUND: Pharmaceutical interventions for diabetes aim to control glycaemia
      and to prevent the development of complications, such as cardiovascular diseases.
      Some anti-hyperglycaemic drugs have been found to have adverse cardiovascular
      effects in their own right, limiting their therapeutic role. Glucokinase activity
      in the pancreas is critical in enhancing insulin release in response to
      hyperglycaemia. Glucokinase activators (GKAs) are novel agents for diabetes which
      act by enhancing the formation of glucose-6-phosphate leading to increased
      insulin production and subsequent suppression of blood glucose. Little, however,
      is known about the direct effects of GKAs on cardiovascular cells. METHODS: The
      effect of the GKAs RO28-1675 and Compound A on glucose utilisation in bovine
      aortic endothelial cells (BAEC) and rat MIN6 was observed by culturing the cells
      at high and low glucose concentration in the presence and absence of the GKAs and
      measuring glucose consumption. The effect of RO28-1675 at various concentrations
      on glucose-dependent signalling in BAEC was observed by measuring Smad2
      phosphorylation by Western blotting. The effect of RO28-1675 on TGF-beta
      stimulated proteoglycan synthesis was measured by 35S-SO4 incorporation and
      assessment of proteoglycan size by SDS-PAGE. The effects of RO28-1675 on TGF-beta
      mediated Smad2C phosphorylation in BAEC was observed by measurement of pSmad2C
      levels. The direct actions of RO28-1675 on vascular reactivity were observed by
      measuring arteriole tone and lumen diameter. RESULTS: GKAs were demonstrated to
      increase glucose utilisation in pancreatic but not endothelial cells. Glucose
      activated Smad2 phosphorylation was decreased in a dose-dependent fashion in the
      presence of RO28-1675. No effect of RO28-1675 was observed on TGF-beta stimulated
      proteoglycan production. RO28-1675 caused a modest dilation in arteriole but not
      contractile sensitivity. CONCLUSIONS: GKA RO28-1675 did not increase glucose
      consumption in endothelial cells indicating the absence of glucokinase in those
      cells. No direct deleterious actions, in terms of atherogenic changes or
      excessive vasoactive effects were seen on cells or vessels of the cardiovascular
      system in response to GKAs. If reflected in vivo, these drugs are unlikely to
      have their use compromised by direct cardiovascular toxicity.

PMID- 24731773
TI  - Forearm pressure distribution during ambulation with elbow crutches: a cross
      sectional study.
AB  - BACKGROUND: Increasing numbers of patients require permanent walking aids to
      maintain mobility. Current elbow crutches are not designed for long-term use, and
      overuse is often associated with hematoma formation and pain along the forearm.
      We therefore hypothesized that the highest pressures between the forearm and
      crutch cuff during walking and stance are located in the ulnar region and that
      the level of weight-bearing, forearm circumference and kinematic parameters
      influence peak pressure values and pressure distribution. METHODS: Ten healthy
      adults participated in a cross-sectional study. A pressure sensor array was
      attached to the forearm of each participant separating the forearm into four
      quadrants (lateral, ulnar, intermediate and medial). Measurements were taken
      during crutch gait and during partial and full weight-bearing stance. A three
      dimensional motion analysis system with reflective markers attached to the
      subject's body and to the crutches was used to obtain kinematic data. RESULTS:
      The mean pressure on the forearm during crutch gait was 37.5 kPa (SD 8.8 kPa).
      Highest mean pressure values were measured in the ulnar (41.0 kPa, SD 9.6 kPa)
      and intermediate (38.0 kPa, SD 9.0 kPa) quadrants. The center of pressure was
      mainly located in an oblique lamellar area in these two quadrants. With
      increasing weight-bearing on the crutches during stance, we observed a shift of
      the peak pressures towards the ulnar quadrant. The circumference of the forearm
      correlated with the peak pressure in the medial and intermediate quadrants during
      crutch gait (P < 0.05). Peak pressures on the forearm showed a trend towards
      correlation with crutch abduction, but no association with other kinematic
      parameters was detected. CONCLUSION: The pressure load on the forearm during
      crutch-assisted gait is located predominantly over the ulna and may be linked to
      a range of secondary conditions caused by crutch use including hematoma formation
      and pain.

PMID- 24731774
TI  - Surface electromyography during physical exercise in water: a systematic review.
AB  - BACKGROUND: Aquatic exercise has been widely used for rehabilitation and
      functional recovery due to its physical and physiological benefits. However,
      there is a high variability in reporting on the muscle activity from surface
      electromyographic (sEMG) signals. The aim of this study is to present an updated
      review of the literature on the state of the art of muscle activity recorded
      using sEMG during activities and exercise performed by humans in water. METHODS:
      A literature search was performed to identify studies of aquatic exercise
      movement. RESULTS: Twenty-one studies were selected for critical appraisal.
      Sample size, functional tasks analyzed, and muscles recorded were studied for
      each paper. The clinical contribution of the paper was evaluated. CONCLUSIONS:
      Muscle activity tends to be lower in water-based compared to land-based activity;
      however more research is needed to understand why. Approaches from basic and
      applied sciences could support the understanding of relevant aspects for clinical
      practice.

PMID- 24731775
TI  - Physiology of Geobacter metallireducens under excess and limitation of electron
      donors. Part I. Batch cultivation with excess of carbon sources.
AB  - For microorganisms that play an important role in bioremediation, the adaptation
      to swift changes in the availability of various substrates is a key for survival.
      The iron-reducing bacterium Geobacter metallireducens was hypothesized to repress
      utilization of less preferred substrates in the presence of high concentrations
      of easily degradable compounds. In our experiments, acetate and ethanol were
      preferred over benzoate, but benzoate was co-consumed with toluene and butyrate.
      To reveal overall physiological changes caused by different single substrates and
      a mixture of acetate plus benzoate, a nano-liquid chromatography-tandem mass
      spectrometry-based proteomic approach (nano-LC-MS/MS) was performed using label
      free quantification. Significant differential expression during growth on
      different substrates was observed for 155 out of 1477 proteins. The benzoyl-CoA
      pathway was found to be subjected to incomplete repression during exponential
      growth on acetate in the presence of benzoate and on butyrate as a single
      substrate. Peripheral pathways of toluene, ethanol, and butyrate degradation were
      highly expressed only during growth on the corresponding substrates. However, low
      expression of these pathways was detected in all other tested conditions.
      Therefore, G. metallireducens seems to lack strong carbon catabolite repression
      under high substrate concentrations, which might be advantageous for survival in
      habitats rich in fatty acids and aromatic hydrocarbons. 

PMID- 24731776
TI  - Do submissions entitled to an auto-waiver take more time to be accepted by open
      access journals?
AB  - BACKGROUND: Open access initiative is a "talk of the town" in scientific
      community in recent years. Many open access publishers have an auto-waiver policy
      for resource limited countries. It is still not documented that whether
      submissions from auto- and non-waiver countries take the same time to be accepted
      by the editorial office or a sense of priority works for non-waiver groups.
      FINDINGS: Analyzing 248 articles published in BMC Research Notes in 2013 we have
      found that average 143.8 +/- 5.134 and 138.4 +/- 12.01 days respectively for non
      waiver and auto-waiver countries were required by the editorial office to accept
      a submission (p = 0.6983). CONCLUSION: From this current investigation it is
      quite evident that both categories of submissions, coming from auto- and non
      waiver countries, are equally treated by the for-profit open access journals and
      thus it can be concluded that no sense of priority works in case of submissions
      those come from non-waiver countries.

PMID- 24731777
TI  - Organometallic compounds in medicine and biology.

PMID- 24731778
TI  - Correlation between long-term in vivo amalgam restorations and the presence of
      heavy elements in the dental pulp.
AB  - PROJECT: To measure the levels of heavy metals (Hg, Sn) in the dental pulp and
      blood samples of patients with long-term amalgam restorations. PROCEDURE: 12
      amalgam restored and 12 non-restored, sound teeth were chosen and access cavity
      preparation to the pulp chamber was made. The contents were transferred and
      dissolved in 5mL of concentrated nitric acid followed by placement in an oven at
      180 degrees C for tissue digestion. After cooling the tubes each digested sample
      was transferred to an atomic absorption system to measure the levels of heavy
      metals. The blood samples of five patients in each group were randomly analyzed
      to determine the levels of these heavy metals in the blood and if there were a
      correlation between these levels in blood and pulp. Data were analyzed by t-test
      at a P<0.05 level of significance. RESULTS: No significant difference was seen
      between the levels of Hg and Sn in pulp tissues (P>0.05); however, the blood
      analysis showed higher level of Hg amalgam group (P=0.009). The analysis between
      the pulp and blood samples showed positive correlations for both Hg and Sn
      elements in dental pulp and the blood (P=1.000) (P=0.900). CONCLUSIONS: The long
      term presence of dental amalgam (at least 5 years) did not result in any
      remarkable changes in the levels of mercury and tin in the pulp tissue; however,
      there were increases in the level of mercury in the blood circulation even five
      years following the placement of the restoration.

PMID- 24731779
TI  - TMEM106B influences volume of left-sided temporal lobe and interhemispheric
      structures in the general population.
AB  - BACKGROUND: Frontotemporal lobar degeneration is a neurodegenerative disease
      characterized by brain atrophy of the frontal and anterior temporal lobes. The
      associated frontotemporal dementia syndromes are clinically heterogeneous, and
      the pattern of affected cortical regions varies among subtypes. The TMEM106B
      rs1990622 polymorphism is associated with frontotemporal lobar degeneration, but
      little is known about how it affects the brain. METHODS: We investigated the
      rs1990622 polymorphism in relation to regional brain volumes to identify
      potential structures through which TMEM106B confers risk for frontotemporal lobar
      degeneration. In 4413 nondemented and stroke-free participants from the
      population-based Rotterdam Study, 150 cortical brain structures and 6 commissural
      regions were segmented from magnetic resonance imaging. RESULTS: A distinct
      pattern of association was found between rs1990622 and gray matter volume of left
      sided temporal brain regions important for language processing, including the
      superior temporal gyrus (beta=-88.8 MUL per risk allele, p=7.64*10(-5)), which
      contains Wernicke's area. The risk allele was also associated with a smaller
      anterior commissure cross-sectional area (beta=-.167 mm2 per risk allele,
      p=4.90*10(-5)) and posterior part of the corpus callosum (beta=-15.3 MUL per risk
      allele, p=1.23*10(-5)), both of which contain temporal lobe commissural tracts.
      CONCLUSIONS: The asymmetric, predominantly left-sided involvement suggests an
      effect of TMEM106B on functions lateralized to the dominant hemisphere, such as
      language. These results show that, in nondemented persons, TMEM106B influences
      the volume of temporal brain regions that are important for language processing.

PMID- 24731780
TI  - Association of apolipoprotein E-e4 and dementia declines with age.
AB  - OBJECTIVE: To study the association of dementia with apolipoprotein E-e4 (APOE
      e4) and its interaction with age in a nonagenarian Costa Rican group (N-sample)
      and a general elderly contrast group (GE-sample). METHODS: In both case-control
      studies, participants were cognitively intact or diagnosed with dementia. The N
      sample (N = 112) was at least age 90 years; the GE-sample (N = 98) was at least
      age 65 years. RESULTS: Dementia and APOE-e4 were not significantly associated in
      the N-sample, but were in the GE-sample. There was a significant interaction of
      age with APOE-e4 in the N-sample, but not in the GE-sample. Descriptively
      dividing the N-sample at the median (age 93 years) showed a group interaction:
      APOE-e4 was more associated with dementia in the younger N-sample than in the
      older N-sample, where six of seven APOE-e4 carriers were cognitively intact.
      CONCLUSIONS: The results support the reduction in association of APOE-e4 with
      dementia in extreme old age, consistent with a survivor effect model for
      successful cognitive aging.

PMID- 24731781
TI  - Association of BDNF promoter methylation and genotype with suicidal ideation in
      elderly Koreans.
AB  - OBJECTIVES: Brain-derived neurotrophic factor (BDNF) has been considered a risk
      factor for suicidal behavior in adult populations. BDNF secretion is influenced
      by epigenetic (DNA promoter methylation) and genetic (val66met polymorphism)
      profiles. We investigated the independent and interactive effects of BDNF
      methylation status and val66met polymorphisms on late-life suicidal ideation.
      METHODS: In total, 732 Korean community residents aged 65+ years were evaluated;
      of 639 without suicidal ideation, 579 (90.6%) were followed up 2 years later. The
      prevalence and incidence of suicidal ideation were ascertained using the
      Geriatric Mental State Schedule. Sociodemographic and clinical covariates
      included age, sex, education, depressive symptoms, cognitive function, and
      disability. The independent effects of BDNF methylation status on the prevalence
      and incidence of suicidal ideation were investigated using multivariate logistic
      regression models. The two-way interactions of BDNF methylation status and
      val66met polymorphism on suicidal ideation were assessed using the same models.
      RESULTS: Higher BDNF methylation status was significantly associated with both
      prevalence and incidence of suicidal ideation, independent of potential
      covariates. No significant methylation-genotype interaction was found.
      CONCLUSIONS: The BDNF hypothesis and the epigenetic origin of the suicidal
      behavior were supported, even in old age. BDNF promoter methylation status may be
      useful as a biological marker for suicidality in late life.

PMID- 24731782
TI  - Prevalence and in-hospital mortality of hyponatremia: a cohort study.

PMID- 24731783
TI  - Natalizumab treatment shows no clinically meaningful effects on immunization
      responses in patients with relapsing-remitting multiple sclerosis.
AB  - Natalizumab is an immunomodulatory drug approved for the treatment of multiple
      sclerosis. This randomized, multicenter, open-label study evaluated natalizumab's
      effects on immunization responses to a recall antigen (tetanus toxoid [TT]) and a
      neoantigen (keyhole limpet hemocyanin [KLH]) in patients with relapsing forms of
      multiple sclerosis (MS). Natalizumab-naive relapsing MS patients were randomized
      (1:1; n=30 per group) to receive TT and KLH immunizations either without
      natalizumab treatment (control) or after 6 months of natalizumab treatment
      (natalizumab group). An adequate response to immunization was defined as an
      increase to at least twofold in specific serum immunoglobulin G (IgG) 28 days
      after the first immunization. All evaluable patients achieved protective levels
      of anti-TT IgG antibodies, and the proportion of responders to this recall
      antigen, as well as to primary immunization with KLH, was similar in the presence
      and absence of natalizumab. This indicates that natalizumab treatment does not
      appear to affect responses to primary or secondary immunization in a clinically
      meaningful way.

PMID- 24731784
TI  - Keratinization induced by air exposure in the reconstructed human epidermal
      model: an in vitro model of a cultured epithelial autograft.
AB  - A reconstructed human epidermis, an in vitro model of a cultured epithelial
      autograft, was used to examine the formation of a stratum corneum induced by
      exposure to air. A prolonged wet condition and excess application of petrolatum
      on the dressing reduced efficient production of the stratum corneum. 

PMID- 24731785
TI  - Binding affinity of ssDNA is improved by attachment of dsDNA regions.
AB  - LidNA, a microRNA inhibitor consisting of a microRNA binding ssDNA region
      sandwiched between dsDNA regions had higher affinity to target oligonucleotides
      than that without dsDNA region. This enhancement in affinity was found to be
      owing to the suppressed mobility of ssDNA region by the presence of dsDNA
      regions. 

PMID- 24731786
TI  - Targeted prostate biopsies: the complexity behind a simple concept.

PMID- 24731787
TI  - Next-generation sequencing of urologic cancers: next is now.
AB  - The exomes/genomes of a few hundred kidney, bladder, and prostate tumours have
      been sequenced. This sequencing has unveiled new genes that are altered and new
      opportunities for tumour subclassification, prediction of outcome, and therapy.
      These opportunities will soon become realities.

PMID- 24731788
TI  - Hepatoprotective effect of fucoidan isolated from the seaweed Turbinaria
      decurrens in ethanol intoxicated rats.
AB  - Fucoidan is the sulfated polysaccharide which is present in the cell wall of the
      brown seaweeds with high nutritive value. It is widely known for its
      pharmacological activity and hence it is added as a main ingredient in the food
      supplements. A water soluble crude polysaccharide was extracted from Turbinaria
      decurrens. Ethanol has been used as a hepatotoxin in vivo and its administration
      increased oxidative stress, decreased antioxidant defence and liver injury.
      Fucoidan treatment increased the body weight, food intake and serum protein
      levels, it decreases the level of hepatic markers. Fucoidan improved the
      antioxidant status of alcoholic rats, which is evaluated by the decreased levels
      of lipid peroxidation markers and increased level of enzymatic antioxidants were
      observed in liver. Histopathological observations and protein expression were
      also in correlation with the biochemical parameters. The hepatoprotective effect
      of fucoidan is probably due to its antioxidant effect. 

PMID- 24731789
TI  - Neonatal total bilirubin measurements: Still room for harmonization.
AB  - BACKGROUND: Universal screening of total bilirubin in neonates is endorsed by
      experts from the American Academy of Pediatrics and is increasingly common.
      Methodological differences between diazo-based quantitation ("wet" chemistry) and
      reflectance spectrophotometric quantitation ("dry" chemistry) can lead to
      unnecessary treatment. A recent recalibration of the only commercially available
      "dry" chemistry assay was issued to reduce these differences. This study
      evaluated the post-recalibration bias between the two assay types. METHODS:
      Method comparison of neonatal total bilirubin (Beckman AU680 vs Ortho-Clinical
      Diagnostics Vitros) was achieved using freshly-drawn neonatal samples (n=239).
      RESULTS: The Vitros produced neonatal bilirubin results with a 12.4% average
      positive bias compared to the AU680 total bilirubin results. The AU680 direct
      bilirubin reaction had 5.6% cross reactivity with unconjugated bilirubin.
      CONCLUSIONS: Neonatal or total bilirubin quantitation remains unharmonized
      between platforms. Care should be taken to understand the bias of specific
      platforms.

PMID- 24731790
TI  - Analytical interference of 4-hydroxy-3-methoxymethamphetamine with the
      measurement of plasma free normetanephrine by ultra-high pressure liquid
      chromatography-tandem mass spectrometry.
AB  - OBJECTIVES: The diagnosis of pheochromocytoma relies on the measurement of plasma
      free metanephrines assay whose reliability has been considerably improved by
      ultra-high pressure liquid chromatography tandem mass spectrometry (UHPLC-MS/MS).
      Here we report an analytical interference occurring between 4-hydroxy-3
      methoxymethamphetamine (HMMA), a metabolite of 3,4-methylenedioxymethamphetamine
      (MDMA, "Ecstasy"), and normetanephrine (NMN) since they share a common
      pharmacophore resulting in the same product ion after fragmentation. DESIGN AND
      METHODS: Synthetic HMMA was spiked into plasma samples containing various
      concentrations of NMN and the intensity of the interference was determined by
      UPLC-MS/MS before and after improvement of the analytical method. RESULTS: Using
      a careful adjustment of chromatographic conditions including the change of the
      UPLC analytical column, we were able to distinguish both compounds. HMMA
      interference for NMN determination should be seriously considered since MDMA
      activates the sympathetic nervous system and if confounded with NMN may lead to
      false-positive tests when performing a differential diagnostic of
      pheochromocytoma.

PMID- 24731791
TI  - Selective screening for inborn errors of metabolism by tandem mass spectrometry
      in Egyptian children: a 5 year report.
AB  - OBJECTIVE: In order to enhance awareness and promote registry for inborn errors
      of metabolism (IEMs) in Egypt, we aimed to evaluate the prevalence and main
      clinical findings of IEMs detectable by tandem mass spectrometry (MS/MS) among
      high risk pediatric patients presenting to our tertiary care facility at Cairo
      University Children's Hospital over a period of 5 years and to compare the
      disease burden in Egypt in the absence of a national screening program for
      inherited metabolic disorders with other populations. METHODS: During this period
      3380 Egyptian children were suspected of having IEMs based on clinical/laboratory
      presentation and were analyzed by MS/MS. Confirmatory testing was performed
      according to flagged analyte by MS/MS using a different sample type such as
      plasma or urine or by a different technique such as GC/MS. RESULTS: A relatively
      high number of patients (203/3380 (6%)) were confirmed with 17 different types of
      IEMs. Averages for age at diagnosis for different disorders ranged from 2.5
      months to 6.6 years with general developmental delay and irreversible
      neurological damage being the most common presenting features (75.9% and 65.5%,
      respectively). Amino acid disorders (127/203 (62.6%)), mainly phenylketonuria
      (100/203 (49.3%)), were the most encountered, followed by organic acidemias
      (69/203 (34%)), while fatty acid oxidation defects (7/203 (3.4%)) were relatively
      rare. 88% of patients were born to consanguineous parents. CONCLUSIONS: The
      development of a nationwide screening program for IEMs is mandatory for early
      detection of these potentially treatable disorders, prompt and properly timed
      therapeutic intervention and prevention of the devastating neurological outcomes.

PMID- 24731792
TI  - Current-density imaging using ultra-low-field MRI with zero-field encoding.
AB  - Electric current density can be measured noninvasively with magnetic resonance
      imaging (MRI). Determining all three components of the current density, however,
      requires physical rotation of the sample or current injection from several
      directions when done with conventional methods. However, the emerging technology
      of ultra-low-field (ULF) MRI, in which the signal encoding and acquisition is
      conducted at a microtesla-range magnetic field, offers new possibilities. The low
      applied magnetic fields can even be switched off completely within the pulse
      sequence, increasing the flexibility of the available sequences. In this article,
      we present a ULF-MRI sequence designed for obtaining all three components of a
      current-density pattern without the need of sample rotations. The sequence
      consists of three steps: prepolarization of the sample, signal encoding in the
      current-density-associated magnetic field without applying any MRI fields, and
      spatial encoding in a microtesla-range field using any standard ULF-MRI sequence.
      The performance of the method is evaluated by numerical simulations. The method
      may find applications, e.g., in noninvasive conductivity imaging of tissue. 

PMID- 24731793
TI  - Earlobe arterialized capillary blood gas analysis in the intensive care unit: a
      pilot study.
AB  - BACKGROUND: Earlobe arterialized capillary blood gas analysis can be used to
      estimate arterial gas content and may be suitable for diagnosis and management of
      critically ill patients. However, its utility and applicability in the ICU
      setting remains unexplored. METHODS: A prospective observational validation study
      was designed to evaluate this technique in a cohort of mechanically ventilated
      adult critically ill patients admitted to a polyvalent ICU. Precision and
      agreement between capillary gas measures and arterial references was examined.
      Acute Respiratory Distress Syndrome (ARDS) diagnosis capabilities with the
      proposed technique were also evaluated. Finally, factors associated with sampling
      failure were explored. RESULTS: Fifty-five patients were included into this
      study. Precision of capillary samples was high (Coefficient of Variation PO2 =
      9.8%, PCO2 = 7.7%, pH = 0.3%). PO2 measures showed insufficient agreement levels
      (Concordance Correlation Coefficient = 0.45; bias = 12 mmHg; percentage of error
      = 19.3%), whereas better agreement was observed for PCO2 and pH (Concordance
      Correlation Coefficient = 0.94 and 0.93 respectively; depreciable bias;
      percentage of error 11.4% and 0.5% respectively). The sensitivity and specificity
      for diagnosing ARDS were 100% and 92.3% using capillary gasometric measures.
      Sampling was unsuccessful in 43.6% of cases due to insufficient blood flow. Age >
      65 years was independently associated with failure (odds ratio = 1.6), however
      hemodynamic failure and norepinephrine treatment were also influencing factors.
      CONCLUSIONS: Earlobe capillary blood gas analysis is precise and can be useful
      for detecting extreme gasometrical values. Diagnosis of ARDS can be done
      accurately using capillary measurements. Although this technique may be
      insufficient for precise management of patients in the ICU, it has the potential
      for important benefits in the acute phase of various critical conditions and in
      other critical care arenas, such as in emergency medicine, advanced medical
      transport and pre-hospital critical care.

PMID- 24731794
TI  - Seroprevalence and transmission of Hepatitis B virus among delivering women and
      their new born in selected health facilities, Addis Ababa, Ethiopia: a cross
      sectional study.
AB  - BACKGROUND: Hepatitis B Virus is a major public health problem worldwide. In 2012
      alone, over 350 million chronic carriers and 1. 2 million annual deaths were
      occurred. Hepatitis B Virus causes 60 to 80% of the world's primary liver cancer
      and nearly 90% infants infected due to vertical transmission are at higher risk
      of developing chronic liver disease and cancer. Hence determining the burden of
      maternal and neonatal Hepatitis B Virus infection is a priority. METHODS: A cross
      sectional study was conducted from July - September 2012 at St. Paul's Hospital
      Millennium Medical College and Selam Health Center, Addis Ababa, Ethiopia. Blood
      samples from delivering mothers (n = 265) and their corresponding cords (n = 265)
      were collected. A pretested questionnaire was used to collect data. Hepatitis B
      Virus surface antigen was detected using Enzyme Linked Immunosorbent Assay.
      Frequency analysis and logistic regression test was used to identify the
      potential risk factors associated with Hepatitis B Virus positivity using SPSS
      Version -15. RESULTS: A total of 265 delivering women with the mean age of 25.8
      years were enrolled in the study. Of these delivering women, 8 (3.0%) of mothers
      were positive for Hepatitis B Virus surface antigen, whereas 6 (2.3%) of cord
      bloods were positives with 75% concordance rate of exposed infants with sero
      positive mothers. However, only one maternal positive case was observed for
      Hepatitis B e Ag test. Only 11% of the mothers know their Hepatitis B Virus
      status. Of the total mothers assessed for possible risk factors, 69 (26%) had
      only one type, while 161 (60.8%) had multiple exposure factors such as ear
      pricing, history of tribal marks, abortion, multiple-sexual partner and history
      of surgical procedures experienced from high to low frequency. The remaining 35
      (13.2%) of the participants had not experienced possible risk factors.
      CONCLUSION: Though the maternal positivity rate was low, the rate of positivity
      in cord bloods was almost equal to those infected mothers. Therefore, screening
      of pregnant mothers and vaccination of infants could help to reduce the
      transmission. To minimize the higher overall risk exposure status of mothers,
      increasing awareness and intensive public health education is also recommended.

PMID- 24731795
TI  - Cortical responses to C-fiber stimulation by intra-epidermal electrical
      stimulation: an MEG study.
AB  - Intra-epidermal electric stimulation (IES) is an alternative to laser stimulation
      for selective activation of cutaneous Adelta-fibers. IES is based on the fact
      that nociceptive fiber terminals are located in the epidermis, whereas receptors
      of other fibers end deep in the dermis. IES can selectively stimulate C-fibers if
      the electrode structure and stimulation parameters are carefully selected.
      However, stable selective stimulation of C-fibers using IES has proven difficult
      and cannot currently be used in clinical settings. The purpose of the present
      study was to determine if IES performed using a modified electrode reliably
      stimulates C-fibers. Magnetoencephalographic responses to IES to the foot were
      measured in seven healthy subjects. IES elicited somatosensory evoked fields in
      all subjects. The mean peak latency was 1,327 +/- 116 ms in the opercular region
      contralateral to the stimulated side, 1,318 +/- 90 ms in the opercular region
      ipsilateral to the stimulated side, and 1350 +/- 139 ms in the primary
      somatosensory cortex. These results indicate that IES performed using the
      modified electrode can selectively stimulate C-fibers and may be a useful tool
      for pain research as well as clinical evaluation of peripheral small fiber
      function.

PMID- 24731796
TI  - Intraoperative indocyanine green fluorescence lymphography to detect chylous
      leakage sites after congenital heart surgery.

PMID- 24731798
TI  - Unusual course of left internal thoracic artery.

PMID- 24731797
TI  - Long-term outcomes of concomitant aortic and mitral valve repair.
AB  - OBJECTIVE: To evaluate the short- and long-term outcomes of concomitant aortic
      (AVr) and mitral (MVr) valve repair. METHODS: This retrospective analysis of
      prospectively collected data identified patients who had undergone AVr and MVr
      surgery from March 1996 to October 2009. Patients were included if they had
      undergone combined repair on the aortic and mitral valves. Excluded were those
      <18 years in whom valve replacement was performed. Data were collected on the
      short-term morbidity and mortality (<30 postoperative days), long-term survival,
      and freedom from valve-related events and echocardiographic outcomes. RESULTS: A
      total of 65 patients underwent AVr and MVr (mean age, 56.4 +/- 15.8 years, 46
      men). Preoperatively, 30 patients (46.1%) had aortic insufficiency (AI) >2+, 20
      patients had AI >=2+ with aortic dilatation (30.7%), and 4 patients (6.1%) had
      aortic dilatation only. Of the 65 patients, 57 had tricuspid (87.6%) and 8 had
      bicuspid aortic valves (12.3%). All patients had mitral insufficiency
      preoperatively. One in-hospital death occurred (1.5%). At discharge, no patient
      had AI >2+ versus 30 patients preoperatively (P < .001), and 7 patients had AI
      >1+ versus 61 patients preoperatively (P < .001). At discharge, the mean left
      ventricular end-diastolic diameter was 48 +/- 7 mm versus 59 +/- 9 mm
      preoperatively (P < .007), and the mean left ventricular end-systolic diameter
      was 33 +/- 5 mm versus 38 +/- 14 mm preoperatively (P = .36). The mean clinical
      follow-up duration was 62 +/- 45 months (median, 50; range, 1-177). At the latest
      follow-up visit, 17 patients were New York Heart Association class >=2 versus 52
      patents preoperatively (P < .001). Four cardiac deaths occurred, and at 1, 5, and
      10 years, the freedom from cardiac death was 100%, 93.4% +/- 3.7%, and 88.5% +/-
      5.9%, respectively. Eight valve reinterventions were required, and the freedom
      from valve reintervention at 1, 5, and 10 years was 95.3% +/- 2.6%, 91.6% +/-
      3.6%, and 78.4% +/- 8.0%, respectively. At 1, 5, and 10 years, the freedom from
      AI 2+ was 98.2% +/- 1.7%, 93.4% +/- 3.7%, and 88.3% +/- 5.8% and the freedom from
      mitral insufficiency 2+ was 96.4% +/- 2.4%, 93.3% +/- 3.8%, and 93.3% +/- 3.8%,
      respectively. CONCLUSIONS: Concomitant AVr/MVr is associated with acceptable
      survival and freedom from valve reintervention.

PMID- 24731799
TI  - Exercise-induced dyspnea is a problem among the general adolescent population.
AB  - RATIONALE: Respiratory symptoms during exercise are common and might limit
      adolescents' ability to take part in physical activity. OBJECTIVE: To estimate
      the prevalence, determinants and consequences of exercise-induced dyspnea (EID)
      on daily life in a general population of 12-13 year old adolescents. METHODS: A
      letter was sent to the parents of all 12-13 year old adolescents in the city of
      Uppsala (n = 3838). Parents were asked to complete a questionnaire together with
      their child on EID, asthma and allergy, consequences for daily life (wheeze, day
      time- and nocturnal dyspnea) and physical activity. The response rate was 60% (n
      = 2309). RESULTS: Fourteen percent (n = 330) reported EID, i.e. had experienced
      an attack of shortness of breath that occurred after strenuous activity within
      the last 12 months. Female gender, ever-asthma and rhinitis were independently
      associated with an increased risk of EID. Ever-asthma was reported by 14.6% (n =
      338), and 5.4% (n = 128) had both EID and ever-asthma. Sixty-one percent (n =
      202) of the participants with EID did not have a diagnosis of asthma. In addition
      to rhinitis, participants with EID reported current wheeze and day-time as well
      as nocturnal dyspnea more often than the group without EID. No difference was
      found in the level of physical activity between participants with and without
      EID. CONCLUSION: Adolescents with undiagnosed exercise-induced dyspnea have
      respiratory symptoms and are affected in daily life but have the same level of
      physical activity as adolescents without exercise-induced respiratory symptoms.

PMID- 24731800
TI  - Improved access in endonasal rhinoplasty: the cross cartilaginous approach.
AB  - BACKGROUND: The popularity of open rhinoplasty has increased such that it is the
      first choice of approach for many surgeons undertaking primary rhinoplasty.
      Despite the benefits of this approach, the drawbacks are often not emphasized. We
      present a review, with quantitative assessment of 24 rhinoplasty patients using
      the cross-cartilaginous incision. This new approach optimizes access without an
      external scar and ligament disruption that ensues after the open approach.
      METHODS: 24 consecutive patients underwent primary rhinoplasty from March 2009 to
      April 2011 using the cross-cartilaginous approach. Preoperative measurements of
      defined anatomical sites of the nose were taken. Independent assessments of the
      postoperative results were undertaken by a surgical resident and a senior nurse
      using preoperative and postoperative photographs using the new Independent
      Rhinoplasty Outcome Score (IROS). Evaluation of patient satisfaction and
      postoperative patient concerns were carried out. RESULTS: The range of
      preoperative measurements (average) were: radix 12-19 mm (15.0), keystone 20-34
      mm (24.5), alar base 14-20 mm (17.0), nose length 48-58 mm (50.2), tip width 11
      25 mm (15.9), and tip projection 21-37 mm (29.6). Three months after the
      operation, the patient satisfaction scores were rated 67% good to excellent, 25%
      were acceptable, and 8% were dissatisfied. After 3 months, 17% of patients
      reported swelling, 0% bruising, 8% irregularities, 8% asymmetry, and 4% airway
      issues. Independent assessment of the photographs showed that overall result was:
      31% good, 56% average, and 13% had no improvement. CONCLUSION: Preoperative
      anatomical measurement allows reliable assessment of nasal characteristics and
      comparison with postoperative outcomes. Our simple grading system for outcome
      assessment in rhinoplasty allows the assessment to be reliable and reproducible
      (IROS). The cross-cartilaginous approach is suitable for a majority of primary
      rhinoplasty patients, providing good access and visibility, although, open
      rhinoplasty is required for selected complex revision cases. CLINICAL
      QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

PMID- 24731801
TI  - Blood flow through sutured and coupled microvascular anastomoses: a comparative
      computational study.
AB  - This study uses computational fluid dynamics (CFD) to model blood flow through
      idealised sutured and coupled arterial anastomoses to investigate the affect of
      each technique on intravascular blood flow. Local flow phenomena are examined in
      detail to study characteristics that potentially initiate thrombus formation; for
      example, changes in velocity profile, wall shear stress (WSS), and shear strain
      rate (SSR). Idealised geometries of sutured and coupled anastomoses were created
      with dimensions identical to microvascular suture material and a commercially
      available coupling device using CFD software. Vessels were modelled as non
      compliant 1 mm diameter ducts, and blood was simulated as a Newtonian fluid, in
      keeping with previous studies. All analyses were steady-state and performed on
      arteries. The sutured simulation revealed a reduced boundary velocity profile;
      high WSS; and high SSR at the suture sites. The coupled anastomosis simulation
      showed a small increase in maximum WSS at the anastomotic region compared to a
      pristine vessel, however, this was less than half that of the sutured model. The
      coupled vessel displayed an average WSS equivalent to a pristine vessel
      simulation. Taken together these observations demonstrate a theoretically more
      thrombogenic profile in a sutured anastomosis when compared to a coupled vessel.
      Data from simulations on a coupled anastomosis reveal a profile that is nearly
      equivalent to that of a pristine vessel. Based purely on the combination of less
      favourable flow properties shown using these idealised arterial models, the
      sutured method is potentially more thrombogenic than a coupled anastomosis. 

PMID- 24731802
TI  - Successful limb salvage with the preexpanded dorsalis pedis flap for heel
      reconstruction.

PMID- 24731803
TI  - Conventional versus ultrasound-assisted liposuction in gynaecomastia surgery: a
      13-year review.
AB  - BACKGROUND: Numerous surgical techniques exist for gynaecomastia treatment.
      Although ultrasound-assisted liposuction (UAL) is thought to be more effective
      than conventional liposuction, to date there remains no objective and direct
      comparison of the two modalities. Hence, a comparative study was performed of a
      single surgeon's experience over 13 years using two definitive parameters, namely
      intraoperative conversion to open excision and postoperative revisional surgery
      rates. METHODS: All gynaecomastia patients treated with UAL or conventional
      liposuction (1999-2012) were retrospectively studied. UAL was only available in
      the private sector and was used for all such patients with no other selection or
      exclusion criteria. RESULTS: A total of 219 patients (384 breasts) with a mean
      age of 29 years (range 12-74) were evaluated. UAL was utilised in 24% of breasts
      (47 patients, 91 breasts). Compared with conventional liposuction, UAL had
      significantly lower rates of intraoperative conversion to open excision (25% vs.
      39%; p<0.05) and postoperative revision (2% vs. 19%; p<0.001) using Fisher's
      exact test. The haematoma rate for each technique was 1%. CONCLUSION: UAL is a
      more effective treatment modality for gynaecomastia than conventional liposuction
      as determined by intraoperative conversion to open surgery and subsequent need
      for revision.

PMID- 24731804
TI  - MoLys2 is necessary for growth, conidiogenesis, lysine biosynthesis, and
      pathogenicity in Magnaporthe oryzae.
AB  - Amino acid biosyntheses are complex but essential processes in growth and
      differentiation of eukaryotic cells. In the budding yeast Saccharomyces
      cerevisiae, the lysine biosynthesis via the alpha-aminoadipate (AA) pathway
      involves several steps, including reduction of AA to AA 6-semialdehyde by AA
      reductase ScLys2. In filamentous fungus Penicillium chrysogenum, disruption of
      the LYS2 gene blocked the lysine biosynthesis but promoted the production of the
      secondary metabolite penicillin. In comparison, little is known about the
      function of AA reductase Lys2 in phytopathogenic fungi. We here characterized the
      functions of MoLys2, a homolog of ScLys2, from the rice blast fungus Magnaporthe
      oryzae. Our results showed that the DeltaMolys2 mutants were auxotrophic for
      lysine. The DeltaMolys2 mutants also exhibited drastic reduction in pathogenicity
      on rice, inducing small disease lesions. Microscopic examination of the lesions
      revealed that the invasive hyphae of DeltaMolys2 mutants were mostly restricted
      to the primary infected leaf sheath cells. In addition, exogenous lysine restored
      the production of conidia and near wild-type appressoria differentiation, and
      rescued the defect of pathogenicity in conidia infection of detached barely and
      rice leaf sheath. Our results indicated that MoLys2 is necessary for lysine
      biosynthesis that affects growth, conidiogenesis, and pathogenicity of the
      fungus. This study does implicate the potential for targeting lysine biosynthesis
      for the development of novel fungicides against M. oryzae. 

PMID- 24731805
TI  - Functional disruption of yeast metacaspase, Mca1, leads to miltefosine resistance
      and inability to mediate miltefosine-induced apoptotic effects.
AB  - Miltefosine (MI) is a novel, potential antifungal agent with activity against
      some yeast and filamentous fungal pathogens. We previously demonstrated in the
      model yeast, Saccharomyces cerevisiae, that MI causes disruption of mitochondrial
      membrane potential and apoptosis-like cell death via interaction with the Cox9p
      sub-unit of cytochrome c oxidase (COX). To identify additional mechanisms of
      antifungal action, MI resistance was induced in S. cerevisiae by exposure to the
      mutagen, ethyl methanesulfonate, and gene mutation(s) responsible for resistance
      were investigated. An MI-resistant haploid strain (H-C101) was created.
      Resistance was retained in the diploid strain (D-C101) following mating,
      confirming dominant inheritance. Phenotypic assessment of individual D-C101
      tetrads revealed that only one mutant gene contributed to the MI-resistance
      phenotype. To identify this gene, the genome of H-C101 was sequenced and 17
      mutated genes, including metacaspase-encoding MCA1, were identified. The MCA1
      mutation resulted in substitution of asparagine (N) with aspartic acid (D) at
      position 164 (MCA1(N164D)). MI resistance was found to be primarily due to
      MCA1(N164D), as single-copy episomal expression of MCA1(N164D), but not two other
      mutated genes (FAS1(T1417I) and BCK2(T104A)), resulted in MI resistance in the
      wild-type strain. Furthermore, an MCA1 deletion mutant (mca1Delta) was MI
      resistant. MI treatment led to accumulation of reactive oxygen species (ROS) in
      MI-resistant (MCA1(N164D)-expressing and mca1Delta) strains and MI-susceptible
      (MCA1-expressing) strains, but failed to activate Mca1 in the MI-resistant
      strains, demonstrating that ROS accumulation does not contribute to the
      fungicidal effect of MI. In conclusion, functional disruption of Mca1, leads to
      MI resistance and inability to mediate MI-induced apoptotic effects. Mca1
      mediated apoptosis is therefore a major mechanism of MI-induced antifungal
      action. 

PMID- 24731806
TI  - Putative RhoGAP proteins orchestrate vegetative growth, conidiogenesis and
      pathogenicity of the rice blast fungus Magnaporthe oryzae.
AB  - Rho GTPases, acting as molecular switches, are involved in the regulation of
      diverse cellular functions. Rho GTPase activating proteins (Rho GAPs) function as
      negative regulators of Rho GTPases and are required for a variety of signaling
      processes in cell development. But the mechanisms underlying Rho GAPs in Rho
      mediated signaling pathways in fungi are still elusive. There are eight RhoGAP
      domain-containing genes annotated in the Magnaporthe oryzae genome. To understand
      the function of these RhoGAP genes, we generated knockout mutants of each of the
      RhoGAP genes through a homologous recombination-based method. Phenotypic analysis
      showed that growth rate of aerial hyphae of the Molrg1 deletion mutant decreased
      dramatically. The DeltaMolrg1 mutant showed significantly reduced conidiation and
      appressorium formation by germ tubes. Moreover, it lost pathogenicity completely.
      Deletion of another Rho GAP (MoRga1) resulted in high percentage of larger or
      gherkin-shaped conidia and slight decrease in conidiation. Appressorial formation
      of the DeltaMoRga1 mutant was delayed significantly on hydrophobic surface, while
      the development of mycelial growth and pathogenicity in plants was not affected.
      Confocal fluorescence microscopy imaging showed that MoRga1-GFP localizes to
      septal pore of the conidium, and this localization pattern requires both LIM and
      RhoGAP domains. Furthermore, either deleting the LIM or RhoGAP domain or
      introducing an inactivating R1032A mutation in the RhoGAP domain of MoRga1 caused
      similar defects as the Morga1 deletion mutant in terms of conidial morphology and
      appressorial formation, suggesting that MoRga1 is a stage-specific regulator of
      conidial differentiation by regulating some specific Rho GTPases. In this regard,
      MoRga1 and MoLrg1 physically interacted with both MoRac1-CA and MoCdc42-CA in the
      yeast two-hybrid and pull-down assays, suggesting that the actions of these two
      GAPs are involved in MoRac1 and MoCdc42 pathways. On the other hand, six other
      putative Rho GAPs (MoRga2 to MoRga7) were dispensable for conidiation, vegetative
      growth, appressorial formation and pathogenicity, suggesting that these Rho GAPs
      function redundantly during fungal development. Taking together, Rho GAP genes
      play important roles in M. oryzae development and infectious processes through
      coordination and modulation of Rho GTPases. 

PMID- 24731808
TI  - Formal training in vaccine safety to address parental concerns not routinely
      conducted in U.S. pediatric residency programs.
AB  - OBJECTIVE: To determine if U.S. pediatric residency programs provide formal
      training in vaccine safety to address parental vaccine concerns. METHODS: An
      electronic survey was mailed to all members of the Association of Pediatric
      Program Directors (APPD) to assess (1) if U.S. pediatric residency programs were
      providing formal vaccine safety training, (2) the content and format of the
      training if provided, and (3) interest in a training module for programs without
      training. Two follow-up surveys were mailed at 2 week intervals. Responses to the
      survey were collected at 4 weeks following the last mailing and analyzed.
      Logistic regression was used to assess the impact of program size on the
      likelihood of vaccine safety training. Pearson's chi square was used to compare
      programs with and without formal vaccine safety training in 5 U.S. regions.
      RESULTS: The survey was sent to 199 APPD members; 92 completed the survey
      (response rate 46.2%). Thirty-eight respondents (41%) had formal training in
      vaccine safety for pediatric residents at their programs; 54 (59%) did not. Of
      those that did not, the majority (81.5%) were interested in formal vaccine safety
      training for their residents. Of all respondents, 78% agreed that training in
      vaccine safety was a high priority for resident education. Thirty-five percent of
      all respondents agreed that local parental attitudes about vaccines influenced
      the likelihood of formal vaccine safety training. CONCLUSION: Most pediatric
      residency programs surveyed do not include formal training on vaccine safety;
      yet, such training is supported by pediatric residency program directors as a
      priority for pediatric residents.

PMID- 24731807
TI  - A new adjuvanted nanoparticle-based H1N1 influenza vaccine induced antigen
      specific local mucosal and systemic immune responses after administration into
      the lung.
AB  - Annually influenza virus infections are responsible for hospitalization and
      mortality, especially in high risk groups. Constant antigenic changes in seasonal
      influenza viruses resulted from antigenic shifts and antigenic drifts, enable
      emerging of novel virus subtypes that may reduce current vaccine efficacy and
      impose the continuous revision of vaccine component. Currently available vaccines
      are usually limited by their production processes in terms of rapid adaptation to
      new circulating subtypes in high quantities meeting the global demand. Thus, new
      approaches to rapidly manufacture high yields of influenza vaccines are required.
      New technologies to reach maximal protection with minimal vaccine doses also need
      to be developed. In this study, we evaluated the systemic and local
      immunogenicity of a new double-adjuvanted influenza vaccine administered at the
      site of infection, the respiratory tract. This vaccine combines a plant-produced
      H1N1 influenza hemagglutinin antigen (HAC1), a silica nanoparticle-based (SiO2)
      drug delivery system and the mucosal adjuvant candidate bis-(3',5')-cyclic
      dimeric guanosine monophosphate (c-di-GMP). Mice were vaccinated by intratracheal
      route with HAC1/SiO2 or HAC1/c-di-GMP (single-adjuvanted vaccine) or HAC1/SiO2/c
      di-GMP (double-adjuvanted vaccine) and evaluated for target-specific immune
      responses, such as hemagglutination inhibition and hemagglutinin-specific IgG
      titers, as well as local antibody (IgG and IgA) titers in the bronchoalveolar
      lavage (BAL). Furthermore, the HAC1-specific T-cell re-stimulation potential was
      assessed using precision-cut lung slices (PCLS) of vaccinated mice. The double
      adjuvanted vaccine induced high systemic antibody responses comparable to the
      systemic vaccination control. In addition, it induced local IgG and IgA responses
      in the BAL. Furthermore, HAC1 induced a local T-cell response demonstrated by
      elevated IL-2 and IFN-gamma levels in PCLS of c-di-GMP-vaccinated mice upon re
      stimulation. Overall, the present study showed the potential of the double
      adjuvanted vaccine to induce systemic humoral immune responses in intratracheally
      vaccinated mice. Furthermore, it induced a strong mucosal immune response, with
      evidence of antigen-primed T-cells in the lung.

PMID- 24731809
TI  - A pan inhibitor of DASH family enzymes induces immunogenic modulation and
      sensitizes murine and human carcinoma cells to antigen-specific cytotoxic T
      lymphocyte killing: implications for combination therapy with cancer vaccines.
AB  - Recent studies have suggested that pan inhibitors of dipeptidyl peptidase-4
      activity and/or structure homologs (DASH), including ARI-4175, can mediate tumor
      regression by immune-mediated mechanisms. This study assessed the potential of
      combining ARI-4175 with cancer vaccines. We evaluated ARI-4175's effect on
      immunogenic modulation, ability to sensitize tumor cells to antigen-specific CTL
      killing, effect on immune-cell subsets and function, and antitumor activity in 2
      tumor models, both as a monotherapy and in combination with a recombinant viral
      or dendritic cell (DC)-based tumor-cell vaccine. ARI-4175's effects on the
      growth, surface phenotype, and antigen-specific CTL-mediated lysis of murine and
      human carcinoma cell lines were assessed in vitro. In vivo, C57BL-6 mice were
      treated orally with ARI-4175, after which splenocytes were assessed by flow
      cytometry and functional assays. Antitumor studies were performed in murine
      models of colon carcinoma (MC38-CEA(+) in CEA-transgenic C57BL-6 mice) and
      rhabdomyosarcoma (M3-9-M in C57BL-6 mice). Mice received oral ARI-4175 alone or
      in combination with a vaccine consisting of recombinant vaccinia/fowlpox CEA
      TRICOM (colon model) or a DC-based tumor-cell vaccine (rhabdomyosarcoma model).
      Exposure to ARI-4175 had no effect on the proliferation or viability of carcinoma
      cells in vitro; however, it did alter tumor phenotype, making murine and human
      tumor cells more sensitive to antigen-specific CTL killing. Assessment of immune
      cell subsets and function indicated that ARI-4175 increased levels of natural
      killer cells and DCs. Detrimental immune effects, including reduced T effector
      cells and increased immunosuppressive cells (Tregs, MDSCs), were normalized when
      treatment stopped, suggesting that scheduling is critical when combining this
      agent with vaccine. As a monotherapy, ARI-4175 had potent antitumor activity in
      both tumor models, and had even greater effects when combined with a vaccine
      (either DC-based or poxviral vector based). These findings provide the rationale
      for the combined use of cancer immunotherapy with DASH enzyme inhibitors such as
      ARI-4175. 

PMID- 24731810
TI  - Effect of different adjuvant formulations on the immunogenicity and protective
      effect of a live Mycoplasma hyopneumoniae vaccine after intramuscular
      inoculation.
AB  - Mycoplasma hyopneumoniae (M. hyopneumoniae) vaccine strain 168 is an
      intrapulmonically injected attenuated live vaccine that is available in the
      Chinese market. The aim of this study was to develop suitable adjuvants for this
      live vaccine to provide effective protection after intramuscular inoculation.
      Several adjuvant components were screened to assess their toxicity for the live
      vaccine, and various adjuvant formulations were then designed and prepared.
      Vaccines supplemented with these adjuvants were used to immunize mice
      intramuscularly to assess the capacity of the adjuvants to induce a specific
      immune response. The screened formulations were then evaluated in pigs. Seven of
      the eight adjuvant components did not affect the viability of the live vaccine,
      and seven different adjuvant formulations were then designed. In mice, the ISCOM
      matrix adjuvant and the levamisole-chitosan mixture adjuvant significantly
      enhanced serum IgG responses against M. hyopneumoniae, while lymphocyte
      proliferation was enhanced by the ISCOM-matrix adjuvant, the carbomer-astragalus
      polysaccharide mixture adjuvant and an oil-in-water emulsion adjuvant. These four
      adjuvants were evaluated in pigs. Enhancement of specific lymphocyte
      proliferation responses was observed in the groups vaccinated with the ISCOM
      matrix adjuvant and the carbomer-astragalus polysaccharide mixture adjuvant.
      Significant enhancement of serum IgG antibody production was observed before
      challenge in pigs vaccinated with the carbomer-astragalus polysaccharide mixture
      adjuvant and the levamisole-chitosan mixture adjuvant, while after challenge, all
      of the animals that received vaccines containing adjuvants had higher antibody
      concentrations against M. hyopneumoniae than unvaccinated animals. Animals
      inoculated with a vaccine containing the ISCOM-matrix adjuvant (median score
      3.57) or the carbomer-astragalus polysaccharide mixture adjuvant (median score
      5.28) had reduced lesion scores compared to unvaccinated animals (median score
      14.81). These studies will help in the development of appropriate adjuvants for
      intramuscular administration of this live M. hyopneumoniae vaccine. 

PMID- 24731811
TI  - Antigenicity and immunogenicity of a novel Plasmodium vivax circumsporozoite
      derived synthetic vaccine construct.
AB  - BACKGROUND: The circumsporozoite (CS) protein is a major malaria sporozoite
      surface antigen currently being considered as vaccine candidate. Plasmodium vivax
      CS (PvCS) protein comprises a dimorphic central repeat fragment flanked by
      conserved regions that contain functional domains involved in parasite invasion
      of host cells. The protein amino (N-terminal) flank has a cleavage region (region
      I), essential for proteolytic processing prior to parasite invasion of liver
      cells. METHODS: We have developed a 131-mer long synthetic polypeptide (LSP)
      named PvNR1R2 that includes the N-terminal flank and the two natural repeat
      variant regions known as VK210 and VK247. We studied the natural immune response
      to this region in human sera from different malaria-endemic areas and its
      immunogenicity in mice. RESULTS: PvNR1R2 was more frequently recognized by sera
      from Papua New Guinea (PNG) (83%) than by samples from Colombia (24%) when tested
      by ELISA. The polypeptide formulated in Montanide ISA51 adjuvant elicited strong
      antibody responses in both C3H and CB6F1 mice strains. Antibodies from immunized
      mice as well as affinity-purified human IgG reacted with native protein by IFA
      test. Moreover, mouse immune sera induced strong (90%) in vitro inhibition of
      sporozoite invasion (ISI) of hepatoma cell lines. CONCLUSIONS: These results
      encourage further studies in non-human primates to confirm the elicitation of
      sporozoite invasion blocking antibodies, to assess cell mediated immune responses
      and the protective efficacy of this polypeptide.

PMID- 24731812
TI  - Anti-diphtheria immunity in Nigerian mothers and their newborns.
AB  - BACKGROUND: Immunity to diphtheria has been noted to wane with age such that
      previous studies have shown that a significant proportion of females with
      characteristics comparable to those of Nigerian women of reproductive age have
      inadequate levels of immunity to diphtheria. Thus, it is envisaged that Nigerian
      newborns may inherit inadequate levels of immunity to diphtheria from their
      mothers. METHODS: Cord blood and peripheral maternal blood samples were collected
      from 231 mother-infant pairs at delivery. Anti-diphtheria antibody titres were
      assayed using Enzyme-linked immunosorbent assay (ELISA) technique. Recruited
      babies were those born at term with normal birth weight. RESULTS: As much as
      29.9% of both mothers and their babies had no protection (antibody titre<0.01
      IU/ml) from diphtheria. Ninety (39.0% CI 33%,45%) mothers and 107 (46.3% CI
      40%,52%) babies were inadequately protected (antibody titre<0.1 IU/ml) from
      diphtheria. The difference in the geometric mean antibody titres of mothers and
      babies was statistically significant (p<0.0001). There was a strong positive
      linear correlation between maternal and newborn antibody titres ("r"=0.983,
      p<0.0001), such that, as mothers antibody titres increased those of their babies
      also increased. CONCLUSION: Significant proportions of Nigerian mothers and
      newborns are at risk of developing diphtheria. Vaccination of parturient women
      with booster doses of diphtheria toxoid vaccine is recommended.

PMID- 24731813
TI  - Mucosal immunization of calves with recombinant bovine adenovirus-3 coexpressing
      truncated form of bovine herpesvirus-1 gD and bovine IL-6.
AB  - Previous studies have suggested an important role of the cytokine adjuvant IL-6
      in the induction of mucosal immune responses in animals, including mice. Here, we
      report the in vivo ability of bovine adenovirus (BAdV)-3 expressing bovine (Bo)
      IL-6, to influence the systemic and mucosal immune responses against bovine
      herpesvirus (BHV)-1 gDt in calves. To co-express both antigen and cytokine, we
      first constructed a recombinant BAdV-3 expressing chimeric gDt.BoIL-6 protein
      (BAV326). Secondly, we constructed another recombinant BAdV-3 simultaneously
      expressing gDt and BoIL-6 using IRES containing a bicistronic cassette gDt
      IRES.IL-6, (BAV327). Recombinant proteins expressed by BAV326 and BAV327 retained
      antigenicity (gDt) and biological activity (BoIL-6). Intranasal immunization of
      calves with recombinant BAV326, BAV327 or BAV308 (gDt alone) resulted in
      demonstrable levels of gDt-specific IgG responses in sera and IgA response in
      nasal secretions, in all animals. In addition, all calves developed complement
      independent neutralizing antibody responses against BHV-1. However, no
      significant difference could be observed in the induction of systemic or mucosal
      immune response in animals immunized with recombinant BAV326 or BAV327 co
      expressing BoIL-6. Moreover, there was no difference in the protection against
      BHV-1 challenge particularly in the amount of virus excretion in the nasal cavity
      in calves immunized with BAV326, BAV327 or BAV308. These data suggest that the
      BoIL-6 had no modulating effect on the induction of gDt specific mucosal and
      systemic immune responses in calves. 

PMID- 24731814
TI  - Vaccination with a Streptococcus pneumoniae trivalent recombinant PcpA, PhtD and
      PlyD1 protein vaccine candidate protects against lethal pneumonia in an infant
      murine model.
AB  - Streptococcus pneumoniae infections continue to cause significant worldwide
      morbidity and mortality despite the availability of efficacious serotype
      dependent vaccines. The need to incorporate emergent strains expressing
      additional serotypes into pneumococcal polysaccharide conjugate vaccines has led
      to an identified need for a pneumococcal protein-based vaccine effective against
      a broad scope of serotypes. A vaccine consisting of several conserved proteins
      with different functions during pathogenesis would be preferred. Here, we
      investigated the efficacy of a trivalent recombinant protein vaccine containing
      pneumococcal choline-binding protein A (PcpA), pneumococcal histidine triad D
      (PhtD), and genetically detoxified pneumolysin (PlyD1) in an infant mouse model.
      We found the trivalent vaccine conferred protection from lethal pneumonia
      challenges using serotypes 6A and 3. The observed protection with trivalent PcpA,
      PhtD, and PlyD1 vaccine in infant mice supports the ongoing study of this
      candidate vaccine in human infant clinical trials. 

PMID- 24731815
TI  - National and state-specific estimates of place of influenza vaccination among
      adult populations - United States, 2011-12 influenza season.
AB  - BACKGROUND: Annual influenza vaccination has been recommended for all persons >=6
      months since the 2010-11 season. New partnerships between public health agencies
      and medical and nonmedical vaccination providers have increased the number of
      vaccination providers and locations where vaccination services are delivered.
      METHODS: Data from the 2011-12 Behavioral Risk Factor Surveillance System (BRFSS)
      were analyzed. Point estimates of place of vaccination and 95% confidence
      intervals were calculated. Multivariable logistic regression and predictive
      marginal modeling were conducted to identify factors associated with vaccination
      settings. RESULTS: Among adults vaccinated during the 2011-12 influenza season, a
      doctor's office was the most common place (38.4%) for receipt of influenza
      vaccination, with stores (e.g., supermarkets or drug stores) (20.1%) the next
      common, and workplaces (17.6%) the third common. Overall, reported vaccination in
      nonmedical settings by state ranged from 32.2% in California to 60.4% in Nevada,
      with a median of 45.8%. Characteristics significantly associated with an
      increased likelihood of receipt of vaccination in nonmedical settings were higher
      education, not having certain identified high-risk conditions, not having had a
      routine checkup in the previous 12 months, and not having a primary doctor for
      health care. Being a member of a racial/ethnic minority group, unemployed or not
      in the work force were significantly associated with a decreased likelihood of
      receipt of vaccination in nonmedical settings. CONCLUSION: Doctor's offices were
      the most common medical setting for adult influenza vaccination; workplaces and
      stores were important nonmedical settings. Increasing access to vaccination
      services in medical and nonmedical settings should be considered as important
      strategies for improving vaccination coverage. These results also can help guide
      development of strategies for achieving Healthy People 2020 objectives for
      influenza vaccination of adult populations.

PMID- 24731816
TI  - Antibody avidity measurements in recipients of Cervarix vaccine following a two
      dose schedule or a three-dose schedule.
AB  - The HPV-16/18 vaccine (Cervarix) is a prophylactic vaccine for the prevention of
      cervical cancer and contains recombinant virus-like particles (VLPs) assembled
      from the L1 major capsid proteins of human papillomavirus (HPV) strains 16 and
      18. Although a correlate of protection has yet to be identified, HPV-specific
      antibodies are thought to prevent virus infection of the genital mucosa.
      Therefore, antigen-specific antibodies as assessed by ELISA or pseudovirion-based
      neutralisation assay are frequently measured in clinical trials to substantiate
      the immune responses induced by the vaccine. Measuring antigen-antibody binding
      avidities, which reflects the degree of affinity maturation in the B-cells, is
      another valuable method to assess the quality of the antibody responses. Here we
      describe the antigen-specific antibody avidities in samples taken from a clinical
      trial examining the feasibility of adopting a two-dose (Months 0 and 6) schedule
      for 9-14 year olds instead of the three-dose schedule (Months 0, 1 and 6).
      Antibody avidity (i.e. avidity index [AI]) was determined in the ELISA by the
      ratio of antibody concentrations in serum samples treated or not with the
      chaotropic agent NaSCN. Importantly, in the comparison between the groups of two
      dose and three-dose recipients, no differences in AIs were observed at Months 7,
      24 and 48. The results suggest that from Month 7 to 48, the quality of the
      antibody response in terms of avidity was similar in the two-dose recipients to
      that in the three-dose recipients. Hence these results support the adoption of a
      two-dose schedule in 9-14 year-old girls.

PMID- 24731817
TI  - Vaccine preventable disease incidence as a complement to vaccine efficacy for
      setting vaccine policy.
AB  - Traditionally, vaccines have been evaluated in clinical trials that establish
      vaccine efficacy (VE) against etiology-confirmed disease outcomes, a measure
      important for licensure. Yet, VE does not reflect a vaccine's public health
      impact because it does not account for relative disease incidence. An additional
      measure that more directly establishes a vaccine's public health value is the
      vaccine preventable disease incidence (VPDI), which is the incidence of disease
      preventable by vaccine in a given context. We describe how VE and VPDI can vary,
      sometimes in inverse directions, across disease outcomes and vaccinated
      populations. We provide examples of how VPDI can be used to reveal the relative
      public health impact of vaccines in developing countries, which can be masked by
      focus on VE alone. We recommend that VPDI be incorporated along with VE into the
      analytic plans of vaccine trials, as well as decisions by funders, ministries of
      health, and regulatory authorities. 

PMID- 24731818
TI  - Glycosylated yellow laccases of the basidiomycete Stropharia aeruginosa.
AB  - Here we describe the identification, purification and characterisation of
      glycosylated yellow laccase proteins from the basidiomycete fungus Stropharia
      aeruginosa. Biochemical characterisation of two yellow laccases, Yel1p and Yel3p,
      show that they are both secreted, monomeric, N-glycosylated proteins of molecular
      weight around 55kDa with substrate specificities typical of laccases, but lacking
      the absorption band at 612nm typical of the blue laccase proteins. Low coverage,
      high throughput 454 transcriptome sequencing in combination with inverse-PCR was
      used to identify cDNA sequences. One of the cDNA sequences has been assigned to
      the Yel1p protein on the basis of identity between the translated protein
      sequence and the peptide data from the purified protein, and the full length gene
      sequence has been obtained. Biochemical properties, substrate specificities and
      protein sequence data have been used to discuss the unusual spectroscopic
      properties of S. aeruginosa proteins in the context of recent theories about the
      differences between yellow and blue laccases. 

PMID- 24731819
TI  - An acetylcholinesterase biosensor based on graphene-gold nanocomposite and
      calcined layered double hydroxide.
AB  - In this study, a novel acetylcholinesterase-based biosensor was fabricated.
      Acetylcholinesterase (AChE) was immobilized onto a glassy carbon electrode (GCE)
      with the aid of Cu-Mg-Al calcined layered double hydroxide (CLDH). CLDH can
      provide a bigger effective surface area for AChE loading, which could improve the
      precision and stability of AChE biosensor. However, the poor
      electroconductibility of CLDHs could lead to the low sensitivity of AChE
      biosensor. In order to effectively compensate the disadvantages of CLDHs,
      graphene-gold nanocomposites were used for improving the electron transfer rate.
      Thus, the graphene-gold nanocomposite (GN-AuNPs) was firstly modified onto the
      GCE, and then the prepared CLDH-AChE composite was immobilized onto the modified
      GCE to construct a sensitive AChE biosensor for pesticides detection. Relevant
      parameters were studied in detail and optimized, including the pH of the
      acetylthiocholine chloride (ATCl) solution, the amount of AChE immobilized on the
      biosensor and the inhibition time governing the analytical performance of the
      biosensor. The biosensor detected chlorpyrifos at concentrations ranging from
      0.05 to 150MUg/L. The detection limit for chlorpyrifos was 0.05MUg/L. 

PMID- 24731820
TI  - The effect of gas double-dynamic on mass distribution in solid-state
      fermentation.
AB  - The mass distribution regularity in substrate of solid-state fermentation (SSF)
      has rarely been reported due to the heterogeneity of solid medium and the lack of
      suitable instrument and method, which limited the comprehensive analysis and
      enhancement of the SSF performance. In this work, the distributions of water,
      biomass, and fermentation product in different medium depths of SSF were
      determined using near-infrared spectroscopy (NIRS) and the developed models.
      Based on the mass distribution regularity, the effects of gas double-dynamic on
      heat transfer, microbial growth and metabolism, and product distribution gradient
      were systematically investigated. Results indicated that the maximum temperature
      of substrate and the maximum carbon dioxide evolution rate (CER) were 39.5
      degrees C and 2.48mg/(hg) under static aeration solid-state fermentation (SASSF)
      and 33.9 degrees C and 5.38mg/(hg) under gas double-dynamic solid-state
      fermentation (GDSSF), respectively, with the environmental temperature for
      fermentation of 30+/-1 degrees C. The fermentation production (cellulase
      activity) ratios of the upper, middle, and lower levels were 1:0.90:0.78 at
      seventh day under SASSF and 1:0.95:0.89 at fifth day under GDSSF. Therefore,
      combined with NIRS analysis, gas double-dynamic could effectively strengthen the
      solid-state fermentation performance due to the enhancement of heat transfer, the
      stimulation of microbial metabolism and the increase of the homogeneity of
      fermentation products. 

PMID- 24731821
TI  - Bioproduction of 4-vinylphenol from corn cob alkaline hydrolyzate in two-phase
      extractive fermentation using free or immobilized recombinant E. coli expressing
      pad gene.
AB  - In situ extractive fermentation was used to produce 4-vinyl derivatives from
      hydroxycinnamic acids extracted from corn cobs by recombinant Escherichia coli
      cells expressing Lactobacillus plantarum phenolic acid descarboxylase (PAD) gene.
      This microorganism mainly produced 4-vinylphenol (4VP) from p-coumaric acid (p
      CA). In the first study , we observed that the concentrations of 4VP are higher
      than 1g/L which had a negative impact on decarboxylation of p-CA to 4VP by
      recombinant E. coli cells. Because of this, and in order to improve the
      downstream process, a two-phase aqueous-organic solvent system was developed. The
      results of the extractive fermentation indicated that it was possible to use
      hydrolyzates as aqueous phase to bioproduce 4VP, and recover simultaneously the
      product in the organic phase containing hexane. The detoxification of pre-treated
      corn cob alkaline hydrolyzate improved 4VP production up to 1003.5mg/L after 24h
      fermentation (QP=41.813mg/Lh). Additionally, preliminary experiments using cells
      immobilized in calcium alginate showed to be a good system for the biotransform
      of p-CA to 4VP in extractive fermentation, although the process hindered
      partially the recovery of 4VP in the organic phase. 

PMID- 24731822
TI  - Higher thermostability of l-lactate dehydrogenases is a key factor in decreasing
      the optical purity of d-lactic acid produced from Lactobacillus coryniformis.
AB  - Lactobacillus coryniformis is known to produce d-lactic acid as a dominant
      fermentation product at a cultivation temperature of approximately 30 degrees C.
      However, the considerable production of l-lactic acid is observed when the
      fermentation temperature is greater than 40 degrees C. Because optically pure
      lactates are synthesized from pyruvate by the catalysis of chiral-specific d- or
      l-lactate dehydrogenase, the higher thermostability of l-LDHs is assumed to be
      one of the key factors decreasing the optical purity of d-lactic acid produced
      from L. coryniformis at high temperature. To verify this hypothesis, two types of
      d-ldh genes and six types of l-ldh genes based on the genomic information of L.
      coryniformis were synthesized and expressed in Escherichia coli. Among the LDHs
      tested, five LDHs showed activity and were used to construct polyclonal
      antibodies. d-LDH1, l-LDH2, and l-LDH3 were found to be expressed in L.
      coryniformis by Western blotting analysis. The half-life values (t1/2) of the
      LDHs at 40 degrees C were estimated to be 10.50, 41.76, and 2311min, and the
      T50(10) values were 39.50, 39.90, and 58.60 degrees C, respectively. In addition,
      the Tm values were 36.0, 41.0, and 62.4 degrees C, respectively, which indicates
      that l-LDH has greater thermostability than d-LDH. The higher thermostability of
      l-LDHs compared with that of d-LDH1 may be a major reason why the enantiopurity
      of d-lactic acid is decreased at high fermentation temperatures. The key enzymes
      characterized will suggest a direction for the design of genetically modified
      lactic acid bacteria to produce optically pure d-lactic acid. 

PMID- 24731823
TI  - Inhibition of inflammatory response in LPS-induced macrophages by 9-KOTE and 13
      KOTE produced by biotransformation.
AB  - Lipid mediators such as the leukotrienes, resolvins and protectins have been
      considered excellent models for the development of new anti-inflammatory drugs,
      due to their high potentiality. Nevertheless, only tiny amounts are available
      from natural sources and they have to be prepared by total synthesis. It is known
      that besides chemical reagents, microorganisms can also promote fatty acid
      oxygenation, via enzymatic reactions. In this context, the aim of this work was
      to produce oxylipids analogues in structure to lipid mediators employing
      microbial biotransformation. To this end, alpha-linolenic acid (ALA) was
      biotransformed by the fungi Aspergillus niger into oxylipids with different
      levels of oxygenation within 24h or 48h. The anti-inflammatory potential of
      products were evaluated by means of NO and TNF-alpha quantification in LPS
      stimulated RAW264.7 macrophage cell line which guided the isolation of the
      regioisomers at m/z [M-H](-) 291, 9-keto-10E,12Z,15Z-octadecatrienoic acid (9
      KOTE) and 13-keto-9Z,11E,15Z-octadecatrienoic acid (13-KOTE). We showed that
      biotransformation represents a powerful strategy for the production of
      potentially interesting candidates for development of anti-inflammation
      therapies. 

PMID- 24731824
TI  - Cloning and characterization of a galactitol 2-dehydrogenase from Rhizobium
      legumenosarum and its application in D-tagatose production.
AB  - Galactitol 2-dehydrogenase (GDH) belongs to the protein subfamily of short-chain
      dehydrogenases/reductases and can be used to produce optically pure building
      blocks and for the bioconversion of bioactive compounds. An NAD(+)-dependent GDH
      from Rhizobium leguminosarum bv. viciae 3841 (RlGDH) was cloned and overexpressed
      in Escherichia coli. The RlGDH protein was purified as an active soluble form
      using His-tag affinity chromatography. The molecular mass of the purified enzyme
      was estimated to be 28kDa by sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis and 114kDa by gel filtration chromatography, suggesting that the
      enzyme is a homotetramer. The enzyme has an optimal pH and temperature of 9.5 and
      35 degrees C, respectively. The purified recombinant RlGDH catalyzed the
      oxidation of a wide range of substrates, including polyvalent aliphatic alcohols
      and polyols, to the corresponding ketones and ketoses. Among various polyols,
      galactitol was the preferred substrate of RlGDH with a Km of 8.8mM, kcat of
      835min(-1) and a kcat/Km of 94.9min(-1)mM(-1). Although GDHs have been
      characterized from a few other sources, RlGDH is distinguished from other GDHs by
      its higher specific activity for galactitol and broad substrate spectrum, making
      RlGDH a good choice for practical applications. 

PMID- 24731825
TI  - Structural and functional significance of the highly-conserved residues in
      Mycobacterium tuberculosis acetohydroxyacid synthase.
AB  - Mycobacterium tuberculosis AHAS is a potential target for the development of
      novel anti-tuberculosis agents. Silico analysis showed that conserved His84 and
      Gln86 residues lie in the catalytic dimer interface of M. tuberculosis AHAS.
      Mutational analyses of these invariants led to significant reduction in their
      activity with reduced affinity toward the substrate. Importantly, mutation of
      Gln86 to Trp abolished complete activity. Further, molecular dynamics simulation
      studies suggested that these residues are likely to play a key role in
      maintaining the Glu85 side chain in the required geometry with N1' atom of ThDP
      during catalysis. In addition, substitution of essential Glu85 by Ala, Asp, and
      Gln led to severe drop in catalytic activity with reduced affinity toward ThDP
      confirming its catalytic role in M. tuberculosis AHAS. 

PMID- 24731826
TI  - Enhancing trimethylolpropane esters synthesis through lipase immobilized on
      surface hydrophobic modified support and appropriate substrate feeding methods.
AB  - Candida sp. 99-125 lipase immobilized on surface hydrophobic modified support and
      appropriate substrate feeding methods were used to improve the synthesis of tri
      substituted trimethylolpropane (TMP) esters, which can be used as raw materials
      for biodegradable lubricants. The proposed novel production method is
      environmentally friendly. Lipase was adsorbed on surface hydrophobic silk fibers
      that were pretreated by amino-modified polydimethylsiloxane. A 5-level-4-factors
      central composite model, including reaction time, temperature, enzyme amount, and
      molar ratio of fatty acid to TMP, was designed to evaluate the interaction of
      process variables in the enzymatic esterification. The water activity was kept
      constant using a LiCl-saturated salt solution. Under the optimum conditions with
      30% enzyme amount and substrates molar ratio 8.4 at 45 degrees C for 47h, the
      total conversion of caprylic acid is 97.3% and the yield of tri-substituted TMP
      esters is 95.5%. The surface hydrophobic treatment resulted in less cluster water
      accumulated on the surface immobilized lipase, which was demonstrated by near
      infrared spectra. Consequently, the optimum temperature and water tolerance of
      immobilized lipase were increased. Two TMP-feeding methods were used to maintain
      high molar ratio of fatty acid to TMP, and increase the final tri-substituted TMP
      esters content exceeding 85% (w/w) in reactant. 

PMID- 24731827
TI  - A pyranose dehydrogenase-based biosensor for kinetic analysis of enzymatic
      hydrolysis of cellulose by cellulases.
AB  - A novel electrochemical enzyme biosensor was developed for real-time detection of
      cellulase activity when acting on their natural insoluble substrate, cellulose.
      The enzyme biosensor was constructed with pyranose dehydrongease (PDH) from
      Agaricus meleagris that was immobilized on the surface of a carbon paste
      electrode, which contained the mediator 2,6-dichlorophenolindophenol (DCIP). An
      oxidation current of the reduced form of DCIP, DCIPH2, produced by the PDH
      catalyzed reaction with either glucose or cellobiose, was recorded under constant
      potential amperometry at +0.25V (vs. Ag/AgCl). The PDH-biosensor was shown to be
      anomer unspecific and it can therefore be used in kinetic studies over broad time
      scales of both retaining- and inverting cellulases (in addition to enzyme
      cocktails). The biosensor was used for real-time measurements of the activity of
      the inverting cellobiohydrolase Cel6A from Hypocrea jecorina (HjCel6A) on
      cellulosic substrates with different morphology (bacterial microcrystalline
      cellulose (BMCC) and Avicel). The steady-state rate of hydrolysis increased
      towards a saturation plateau with increasing loads of substrate. The experimental
      results were rationalized using a steady-state rate equation for processive
      cellulases, and it was found that the turnover for HjCel6A at saturating
      substrate concentration (i.e. maximal apparent specific activity) was similar
      (0.39-0.40s(-1)) for the two substrates. Conversely, the substrate load at half
      saturation was much lower for BMCC compared to Avicel. Biosensors covered with a
      polycarbonate membrane showed high operational stability of several weeks with
      daily use. 

PMID- 24731828
TI  - Identification of UshA as a major enzyme for NAD degradation in Escherichia coli.
AB  - Nicotinamide adenine dinucleotide (NAD) and its reduced form NADH are essential
      cofactors for many redox biocatalysts. Because these cofactors are consumed in
      stoichiometric amounts, whole-cell biocatalysts have been routinely employed in
      order to reduce the costs. To further improve the efficacy of redox biocatalysts,
      it is essential to maintain the stability of nicotinamide cofactors, for which it
      is attractive to block degradation pathways for NAD(H). While the biosynthesis of
      NAD(H) has been well studied, it is less understood how NAD(H) are degraded. Here
      we demonstrated that UshA was a major periplasmic enzyme for NAD degradation in
      Escherichia coli. Purified recombinant UshA showed high pyrophosphatase activity
      with the catalytic efficiencies for hydrolysis of NAD and NADH at 3.7MUM(-1)s(-1)
      and 1.4MUM(-1)s(-1), respectively. Deletion of the ushA gene from the chromosome
      led to faster cell growth and improved extracellular NAD stability by 3-fold
      under conditions similar to whole-cell biocatalysis. These results significantly
      enriched our understanding on NAD metabolism, and should facilitate many
      applications including designing more robust redox biocatalysts. 

PMID- 24731829
TI  - A novel GH43 alpha-l-arabinofuranosidase of Penicillium chrysogenum that
      preferentially degrades single-substituted arabinosyl side chains in arabinan.
AB  - We previously described three alpha-l-arabinofuranosidases (ABFs) secreted by
      Penicillium chrysogenum 31B. Here, we purified a fourth ABF, termed PcABF43A,
      from the culture filtrate. The molecular mass of the enzyme was estimated to be
      31kDa. PcABF43A had the highest activity at 35 degrees C and at around pH 5. The
      enzyme activity was strong on sugar beet l-arabinan but weak on debranched
      arabinan and arabinoxylan. Low molecular-mass substrates such as p-nitrophenyl
      alpha-l-arabinofuranoside, alpha-1,5-l-arabinooligosaccharides, and branched
      arabinotriose were highly resistant to the action of PcABF43A. (1)H-NMR analysis
      revealed that PcABF43A hydrolyzed arabinosyl side chains linked to C-2 or C-3 of
      single-substituted arabinose residues in l-arabinan. Reports concerning enzymes
      specific for l-arabinan are quite limited. Pcabf43A cDNA encoding PcABF43A was
      isolated by in vitro cloning. The deduced amino acid sequence of the enzyme shows
      high similarities with the sequences of other fungal uncharacterized proteins.
      Semi-quantitative RT-PCR analysis indicated that the Pcabf43A gene was
      constitutively expressed in P. chrysogenum 31B at a low level, although the
      expression was induced with pectic components such as l-arabinose, l-rhamnose,
      and d-galacturonic acid. Analysis of enzymatic characteristics of PcABF43A, GH51
      ABF (AFQ1), and GH54 ABF (AFS1) from P. chrysogenum suggested that PcABF43A and
      AFS1 function as debranching enzymes and AFQ1 plays a role of saccharification in
      the degradation of l-arabinan by this fungus. 

PMID- 24731830
TI  - Chain length selectivity during the polycondensation of siloxane-containing
      esters and alcohols by immobilized Candida antarctica lipase B.
AB  - We have examined the chain length selectivity for a series of acyl donors by
      lipase B from Candida antarctica (CalB). CalB accepted aliphatic diesters of C4,
      C6 and C12 chain lengths equally. The introduction of a carbon-carbon double bond
      into the C4 esters dramatically lowered the rate constant associated with
      polymerization highlighting the role of geometry in catalysis; fumarate esters
      were polymerized at a reduced rate compared to the succinate esters, while the
      maleate esters were not polymerized above 5% over the course of 24h. A disiloxane
      containing diester impeded catalysis by CalB. We examined a series of vinyl
      siloxane esters and alcohols, and learned that the Z arrangement around the
      double bond stalled esterification by CalB completely. The distance between the
      ester carbonyl and the dimethylsiloxy group was shown to be an important factor
      in mediating catalysis. The rate constants were similar when the methylene spacer
      was 3, 4, or 5 units in length; beyond 6 methylene units, the rate constants
      increased. This has been tentatively attributed to the local reduction on the
      steric bulk when the larger siloxane moiety lies outside of the active site of
      the enzyme. 

PMID- 24731831
TI  - Novel anticoagulants should NOT be recommended for high-risk activity.

PMID- 24731832
TI  - Effects of hiking at moderate and low altitude on cardiovascular parameters in
      male patients with metabolic syndrome: Austrian Moderate Altitude Study.
AB  - OBJECTIVE: Physical activity is a cornerstone in therapy for patients with
      metabolic syndrome. Walking and hiking in a mountain scenery represents an ideal
      approach to make them move. The Austrian Moderate Altitude Study (AMAS) 2000 main
      study is a randomized controlled trial to investigate the cardiovascular effects
      of hiking at moderate altitude on patients with metabolic syndrome compared with
      a control group at low altitude, to assess a potential altitude-specific effect.
      METHODS: Seventy-one male patients with metabolic syndrome were randomly assigned
      to a moderate altitude group (at 1700 m), with 36 participants, or to a low
      altitude group (at 200 m), with 35 participants. The 3-week vacation program
      included 12 hiking tours (4 per week, average duration 2.5 hours, intensity 55%
      to 65% of heart rate maximum). Physical parameters, performance capacity, 24-hour
      blood pressure, and heart rate profiles were obtained before, during, and after
      the stay. RESULTS: In both groups, we found a significant mean weight loss of 
      3.13 kg; changes in performance capacity were minor. Systolic, diastolic, and
      mean arterial pressures and circadian heart rate profiles were significantly
      reduced in both groups, with no differences between them. Consequently, the
      pressure-rate product was reduced as well. All study participants tolerated the
      vacation well without any adverse events. CONCLUSIONS: A 3-week hiking vacation
      at moderate or low altitude is safe for patients with metabolic syndrome and
      provides several improvements in their cardiovascular parameters. The
      cardiovascular benefits achieved are more likely to be the result of regular
      physical activity than the altitude-specific effect of a mountain environment.

PMID- 24731833
TI  - Obsessions appear after the removal a brain tumor in the right frontal lobe.
AB  - A series of case reports and neuroimaging research points to the underlying
      neuropathological substrate for obsessive-compulsive disorder (OCD) and the
      underlying associations between OCD and areas of the frontal lobe. We report a
      patient wherein the onset of OCD occurred after resection of meningioma of the
      right frontal lobe and who was treated successfully with paroxetine
      hydrochloride. We suggest that the onset of secondary (organic) OCD is associated
      with the frontal lobe, and we propose that the origin of obsessions is located in
      the right frontal lobe.

PMID- 24731834
TI  - Management of psychiatric symptoms in anti-NMDAR encephalitis: a case series,
      literature review and future directions.
AB  - Anti-NMDA receptor (NMDAR) encephalitis, formally recognized in 2007, has been
      increasingly identified as a significant cause of autoimmune and paraneoplastic
      encephalitis. Approximately 80% of the patients are females. The characteristic
      syndrome evolves in several stages, with approximately 70% of the patients
      presenting with a prodromal phase of fever, malaise, headache, upper respiratory
      tract symptoms, nausea, vomiting and diarrhoea. Next, typically within two weeks,
      patients develop psychiatric symptoms including insomnia, delusions,
      hyperreligiosity, paranoia, hallucinations, apathy and depression. Catatonic
      symptoms, seizures, abnormal movements, autonomic instability, memory deficits
      may also develop during the course of the disease. Presence of antibodies against
      the GluN1 subunit of the NMDAR in the CSF and serum confirm the diagnosis of
      NMDAR encephalitis, which also should prompt a thorough search for an underlying
      tumor. Age, gender, and ethnicity may all play a role, as black females older
      than 18 years of age have an increased likelihood of an underlying tumor.
      Treatment is focused on tumor resection and first-line immunotherapy
      [corticosteroids, plasma exchange, and intravenous immunoglobulin]. In non
      responders, second- line immunotherapy [rituximab or cyclophosphamide or
      combined] is required. More than 75% of the patients recover completely or have
      mild sequelae, while the remaining patients end up demonstrating persistent
      severe disability or death. There is a paucity of literature on the management of
      psychiatric symptoms in this population. Given the neuropsychiatric symptoms in
      the relatively early phase of the illness, approximately 77 % of the patients are
      first evaluated by a psychiatrist. Earlier recognition of this illness is of
      paramount importance as prompt diagnosis and treatment can potentially improve
      prognosis. We describe two patients diagnosed with NMDAR encephalitis presenting
      with two different psychiatric manifestations. The first patient presented with
      psychotic mania and catatonic symptoms, while the second suffered from depression
      with psychotic and catatonic features refractory to psychotropic medications. We
      review of the use of psychotropic medications and ECT to address insomnia,
      agitation, psychosis, mood dysregulation and catatonia in NMDAR encephalitis.

PMID- 24731835
TI  - Prevalence and characterization of uropathogenic Escherichia coli harboring
      plasmid-mediated quinolone resistance in a Tunisian university hospital.
AB  - The prevalence of plasmid-mediated quinolone resistance (PMQR) determinants was
      investigated in a Tunisian collection of 300 uropathogenic Escherichia coli. PMQR
      genes were detected in 68 isolates (22.7%) as follows: aac(6')-Ib-cr (n=66),
      qnrB1 (n=3), qnrA6 (n=1), and qnrS1 (n=1). Three isolates carried the 2
      determinants aac(6')-Ib-cr and qnrB1. aac(6')-Ib-cr was usually carried on IncF
      type plasmids (n=47/60) and frequently associated with blaCTX-M-15 (n=60).
      Substitutions in gyrA and parC genes were detected in 57.5% of strains. A major
      cluster including 29 isolates was individualized, 28 of them belonged to the
      virulent ST131 clone. In our hospital, the high prevalence of PMQR in E. coli
      isolates was due to horizontal transfer but also to the spread of ST131 clone. 

PMID- 24731836
TI  - Multiplex PCR assays for the detection of Vibrio alginolyticus, Vibrio
      parahaemolyticus, Vibrio vulnificus, and Vibrio cholerae with an internal
      amplification control.
AB  - A multiplex polymerase chain reaction (PCR) assay that can simultaneously detect
      4 major Vibrio spp., Vibrio alginolyticus, Vibrio parahaemolyticus, Vibrio
      vulnificus, and Vibrio cholerae, in the presence of an internal amplification
      control (IAC) was developed. Species-specific PCR primers were designed based on
      the gyrB gene for V. alginolyticus, the collagenase gene for V. parahaemolyticus,
      the vvhA gene for V. vulnificus, and the ompW gene for V. cholerae. Additionally,
      an IAC primer pair was designed in conserved regions of the bacterial 16S rRNA
      gene that is used to indicate false-negative results. A multiplex PCR method was
      developed after optimization of the reaction conditions. The specificity of the
      PCR was validated by using 83 Vibrio strains and 10 other non-Vibrio bacterial
      species. The detection limit of the PCR was 10 CFU per tube for V. alginolyticus,
      V. parahaemolyticus, V. vulnificus, and 10(5) CFU per tube for V. cholerae in
      mixed conditions. This method was used to identify 69 suspicious Vibrio isolates,
      and the results were consistent with physiological and biochemical tests. This
      multiplex PCR method proved to be rapid, sensitive, and specific. The existence
      of IAC could successfully eliminate false-negative results for the detection of
      V. alginolyticus, V. parahaemolyticus, V. vulnificus, and V. cholerae. 

PMID- 24731837
TI  - Evaluation of avibactam-supplemented combination disk tests for the detection of
      OXA-48 carbapenemase-producing Enterobacteriaceae.
AB  - The ability of various combination disk tests (CDTs) incorporating avibactam to
      detect OXA-48 carbapenemase-producing Enterobacteriaceae was evaluated. The CDT
      using 30-MUg temocillin alone and supplemented with 5-MUg avibactam showed good
      performance and could be an adjunctive test to the classic CDT containing class A
      and class B carbapenemase inhibitors for the positive discrimination of OXA-48
      carbapenemase producers from carbapenemase-negative strains. 

PMID- 24731838
TI  - Results of the 4th scientific workshop of the ECCO (I): pathophysiology of
      intestinal fibrosis in IBD.
AB  - The fourth scientific workshop of the European Crohn's and Colitis Organization
      (ECCO) focused on the relevance of intestinal fibrosis in the disease course of
      inflammatory bowel disease (IBD). The objective was to better understand the
      pathophysiological mechanisms of intestinal fibrosis, to identify useful markers
      and imaging modalities of fibrosis in order to assess its presence and
      progression, and, finally, to point out possible approaches for the prevention
      and the treatment of fibrosis. The results of this workshop are presented in
      three separate manuscripts. This first section describes the most important
      mechanisms that contribute to the initiation and progression of intestinal
      fibrosis in IBD including the cellular and molecular mediators, the extracellular
      matrix molecules and matrix metalloproteinases/tissue inhibitors of
      metalloproteinases-system, the microbiota products, the role of fat, genetic and
      epigenetic factors, as well as the currently available experimental models.
      Furthermore, it identifies unanswered questions in the field of intestinal
      fibrosis and provides a framework for future research. 

PMID- 24731839
TI  - Action and target sites of nitric oxide in chloroplasts.
AB  - Nitric oxide (NO) is an important signalling molecule in plants under
      physiological and stress conditions. Here we review the influence of NO on
      chloroplasts which can be directly induced by interaction with the photosynthetic
      apparatus by influencing photophosphorylation, electron transport activity and
      oxido-reduction state of the Mn clusters of the oxygen-evolving complex or by
      changes in gene expression. The influence of NO-induced changes in the
      photosynthetic apparatus on its functions and sensitivity to stress factors are
      discussed.

PMID- 24731841
TI  - Functional analysis of an orange-spotted grouper (Epinephelus coioides)
      interferon gene and characterisation of its expression in response to nodavirus
      infection.
AB  - We cloned and sequenced 2C I-IFN, a two-cysteine containing type I interferon (I
      IFN) gene, in orange-spotted grouper (Epinephelus coioides). The cDNA has 769
      base pairs, the protein has 172 amino acids, and the predicted signal peptide has
      18 amino acids with two cysteines. This gene is similar to I-FNs from sea bass
      and other teleosts. 2C I-IFN has 5 exons and 4 introns, also similar to other
      teleost I-IFNs. Immunohistochemical (IHC) analysis indicated that expression is
      predominantly membrane-localized in healthy grouper, but has a zonal distribution
      in nodavirus-infected grouper. Grouper infected with nodavirus had elevated
      levels of 2C I-IFN at 72 h and Mx at days 6-7. Recombinant 2C I-IFN activated
      grouper Mx, leading to upregulated antiviral activity. The grouper Mx promoter
      was highly induced after treatment with recombinant 2C I-IFN. The present results
      suggest that expression of grouper 2C I-IFN may participate in the immunologic
      barrier function against nodavirus.

PMID- 24731842
TI  - The child neurology match: where have we been and where are we going?

PMID- 24731840
TI  - Altered neuronal and endothelial nitric oxide synthase expression in the bladder
      and urethra of cyclophosphamide-treated rats.
AB  - Increased nitric oxide (NO) production seems to play a key role in
      cyclophosphamide (CYP)-induced cystitis, although the underlying mechanisms and
      the relative involvement of the different NO synthase (NOS) isoforms remain to be
      elucidated. Moreover, the role of the urethra in this process is also unclear. In
      this study, we have analyzed the changes in the expression and distribution of
      the inducible (iNOS), endothelial (eNOS) and neuronal (nNOS) isoforms of NOS, and
      the alterations in nerve-mediated contractility in the bladder and urethra of CYP
      treated rats. Accordingly, Wistar rats were treated with 150 mg kg(-1) CYP for 4
      (acute treatment) or 48 h (intermediate treatment), or with 70 mg kg(-1) CYP
      every 3 days for 10 days (chronic treatment), and the changes in protein
      expression were assessed by immunohistofluorescence and in Western blots, while
      mRNA expression was assessed by conventional and quantitative PCR. Similarly,
      nerve-mediated contractility was analyzed in vitro. Unexpectedly, no iNOS
      expression was detected in CYP-treated animals, while a transient downregulation
      of nNOS expression and a progressive upregulation of eNOS was observed, although
      the eNOS accumulated was not in the active phosphorylated form. Qualitative
      changes in mRNA expression were also observed in the bladder and urethra,
      although contractility only diminished in the bladder and this change was not
      dependent on NOS activity. These findings suggest that spatiotemporal alterations
      in NO production by constitutive NOS may be involved in the pathogenicity of CYP.
      Further studies will be necessary to understand the contribution of eNOS to the
      increases in NO associated with bladder inflammation, or that of free radicals.

PMID- 24731843
TI  - Predictors of recording an event during prolonged inpatient video
      electroencephalogram monitoring in children.
AB  - BACKGROUND: Distinguishing between seizures and nonepileptic events is a key
      challenge in pediatric neurology. The diagnostic gold standard is prolonged
      inpatient video electroencephalogram monitoring. However, little is known about
      preadmission characteristics that are predictive of recording an event during
      such monitoring. METHODS: This is a retrospective chart review of children
      undergoing prolonged inpatient video electroencephalogram monitoring between 2009
      and 2012 at a tertiary referral center for the purpose of distinguishing between
      seizures and nonepileptic events. Demographic information, medical history, event
      characteristics, and inpatient monitoring course were abstracted. RESULTS: Two
      hundred thirteen children were identified. The median recording duration was 25
      hours (interquartile range 22.4-48.5), and median time to event of interest
      (among those with an event recorded) was 4.5 hours (interquartile range 1.4
      18.8). An event of interest was recorded in 66% of patients. At the event level,
      20% of recorded events were associated with an electroencephalogram correlate,
      which refers to a change in the pattern seen on the electroencephalogram during a
      seizure. At the patient level, 112 (79.4%) with events recorded had only
      nonepileptic events recorded, 25 (17.7%) had only seizures recorded, and 4 (2.8%)
      had both recorded. Recording an event was predicted by the presence of
      intellectual disability (P = 0.001), greater preadmission event frequency (P <
      0.001), and shorter latency since most recent event (P < 0.001). CONCLUSIONS:
      Prolonged inpatient electroencephalogram monitoring captured an event of interest
      in two-thirds of patients, with most of these events captured within less than
      four and a half hours of recording onset. Several factors predict a greater yield
      with prolonged inpatient video electroencephalogram monitoring--including event
      frequency, latency since the most recent event, and the presence of intellectual
      disability--and can be used to counsel patients regarding this study for the
      purpose of event capture in the context of shared decision making.

PMID- 24731844
TI  - Clinical, radiological, and genetic survey of patients with muscle-eye-brain
      disease caused by mutations in POMGNT1.
AB  - BACKGROUND: To evaluate clinical, genetic, and radiologic features of our
      patients with muscle-eye-brain disease. METHODS: The data of patients who were
      diagnosed with muscle-eye-brain disease from a cohort of patients with congenital
      muscular dystrophy in the Division of Pediatric Neurology of Dokuz Eylul
      University School of Medicine and Gaziantep Children's Hospital between 2005 and
      2013 were analyzed retrospectively. RESULTS: From a cohort of 34 patients with
      congenital muscular dystrophy, 12 patients from 10 families were diagnosed with
      muscle-eye-brain disease. The mean age of the patients was 9 +/- 5.5 years (2-19
      years). Mean serum creatine kinase value was 2485.80 +/- 1308.54 IU/L (700-4267
      IU/L). All patients presented with muscular hypotonia at birth followed by
      varying degrees of spasticity and exaggerated deep tendon reflexes in later
      stages of life. Three patients were able to walk. The most common ophthalmologic
      and radiologic abnormalities were cataracts, retinal detachment, periventricular
      white matter abnormalities, ventriculomegaly, pontocerebellar hypoplasia, and
      multiple cerebellar cysts. All of the patients had mutations in the POMGNT1 gene.
      The most common mutation detected in 66% of patients was c.1814 G > A (p.R605H).
      Two novel mutations were identified. CONCLUSIONS: We suggest that muscle-eye
      brain disease is a relatively common muscular dystrophy in Turkey. It should be
      suspected in patients with muscular hypotonia, increased creatine kinase, and
      structural eye and brain abnormalities. The c.1814 G > A mutation in exon 21 of
      the POMGNT1 gene is apparently a common mutation in the Turkish population.
      Individuals with this mutation show classical features of muscle-eye-brain
      disease, but others may exhibit a milder phenotype and retain the ability to walk
      independently. Congenital muscular dystrophy patients from Turkey carrying the
      clinical and radiologic features of muscle-eye-brain disease should be evaluated
      for mutations in POMGNT1 gene.

PMID- 24731845
TI  - Posterior reversible encephalopathy and cerebral vasoconstriction in a patient
      with hemolytic uremic syndrome.
AB  - BACKGROUND: We report a patient with hemolytic uremic syndrome who presented with
      radiological manifestations suggestive of posterior reversible encephalopathy
      syndrome and reversible cerebral vasoconstriction syndrome. PATIENT: A 13-year
      old girl presented with fever and bloody diarrhea and progressed to develop
      hemolytic uremic syndrome. She subsequently developed encephalopathy, aphasia,
      and right-sided weakness. RESULTS: Brain magnetic resonance imaging showed
      presence of vasogenic edema in the left frontal lobe, in addition to T2 and fluid
      attenuated inversion recovery changes in white matter bilaterally, compatible
      with posterior reversible encephalopathy syndrome. Magnetic resonance angiography
      showed beading of the cerebral vessels. Neurological deficits reversed 8 days
      after symptom onset, with resolution of the beading pattern on follow-up magnetic
      resonance angiography after 3 weeks, suggesting reversible cerebral
      vasoconstriction syndrome. CONCLUSIONS: Both posterior reversible encephalopathy
      syndrome and reversible cerebral vasoconstriction syndrome may represent
      manifestations of similar underlying pathophysiologic mechanisms. Recognition of
      the co-existence of these processes in patients with hemolytic uremic syndrome
      may aid in judicious management of these patients and avoidance of inappropriate
      therapeutic interventions.

PMID- 24731846
TI  - Cardiac myxoma causing acute ischemic stroke in a pediatric patient and a review
      of literature.
AB  - BACKGROUND: Ischemic stroke in the pediatric population is a rare occurrence, and
      its possible causes span a wide differential that includes atrial myxomas.
      Myxomas are friable cardiac tumors that produce "showers" of emboli resulting in
      transient neurological deficits, cutaneous eruptions, and ophthalmologic
      deficits. PATIENT: We present an 11-year-old boy with a months-long history of an
      intermittent spotted "rash" who presented with acute ischemic stroke caused by a
      left atrial myxoma. We also review clinical features in all 16 other cases of
      cardiac myxoma causing pediatric stroke reported in the literature. RESULTS: Our
      case, along with the review of the literature, highlights the fact that myxomas
      often initially present as stroke with acute hemiplegia and transient cutaneous
      eruptions due to fragmentation of the tumor. CONCLUSIONS: Cardiac myxoma should
      be considered in any child presenting with ischemic stroke, and transient skin
      findings may provide an important diagnostic clue prior to onset of neurological
      symptoms.

PMID- 24731847
TI  - Epilepsy in patients with duplications of chromosome 14 harboring FOXG1.
AB  - BACKGROUND: Dup(14q12) harboring FOXG1 has been recently reported in individuals
      with developmental delay of variable severity, delayed/absent speech, and
      epilepsy/infantile spasms. FOXG1 was described as a dosage-sensitive gene
      encoding G1, a forkhead protein that is a brain-specific transcription factor
      with a role in brain development. PATIENTS: We extensively reviewed all published
      cases with dup(14) harboring FOXG1 and highlighted those epileptological features
      that are more commonly found among such cases. We also describe one new patient,
      detailing his peculiar clinical and neurophysiological findings. RESULTS: To
      date, 15 patients with dup(14) including FOXG1 have been reported; within those
      patients, nine also presented with epilepsy. At onset, the more frequent seizure
      type in the report and also in our patient is the epileptic spasm. Focal seizures
      might also be present. Outcomes in patients with epilepsy associated with dup(14)
      should be considered separately regarding seizures and cognitive and motor
      development. In the majority of patients (seven of 10, including ours), seizures
      tend to disappear and motor skills improve; however, instead stagnation of
      cognitive development is evident in all of them, associated with severe speech
      difficulties. CONCLUSIONS: There are some common features that should be
      considered: seizures with onset during the first year of life, particularly
      clusters of spasms and focal seizures with hypsarrhythmic electroencephalograph
      pattern; different degrees of cognitive impairment possibly associated with
      behavior disturbances and severe speech disabilities; and dysmorphic features in
      the absence of significant microcephaly.

PMID- 24731848
TI  - Late-onset nonketotic hyperglycinemia with a heterozygous novel point mutation of
      the GLDC gene.
AB  - BACKGROUND: Atypical nonketotic hyperglycinemia is characterized by heterogeneous
      phenotypes that often include nonspecific behavioral problems, cognitive
      deficits, and developmental delays. PATIENT: We describe a girl with late-onset
      nonketotic hyperglycinemia presenting at 5 years of age with hypotonia, chorea,
      ataxia, and alterations in consciousness in the setting of febrile illness.
      RESULTS: Serum amino acid analysis was mildly elevated; however, urine amino acid
      analysis was instrumental in demonstrating marked hyperglycinuria. Mutation
      testing showed a heterozygous novel sequence change/point mutation in the glycine
      decarboxylase gene. CONCLUSIONS: This patient illustrates the importance of
      obtaining urine amino acids in individuals whose clinical manifestations are
      suspicious for any form of nonketotic hyperglycinemia, because this testing may
      provide more prominent evidence of elevations in glycine. She also illustrates
      the potential for a heterozygous mutation to result in manifestations of an
      atypical form of nonketotic hyperglycinemia.

PMID- 24731849
TI  - Dancing eyes and clumsy feet.

PMID- 24731850
TI  - Cryopreservation of turkey semen: effect of breeding line and freezing method on
      post-thaw sperm quality, fertilization, and hatching.
AB  - Cryopreservation methods for poultry semen are not reliable for germplasm
      preservation, especially for turkeys, where fertility rates from frozen/thawed
      semen are particularly low. The objective was to evaluate cryopreservation
      methods for effectiveness in promoting cryosurvival and post-thaw function of
      sperm from five turkey lines: one commercial line and four research (RBC1; E;
      RBC2; F) lines from Ohio State University (OSU). The model for cryopreservation
      was set up as a 2*2*2*5 design for cryoprotectant (glycerol or dimethylacetamide
      (DMA)), cryopreservation medium (Lake or ASG), method of dilution (fixed dilution
      volume versus fixed sperm concentration) and turkey line, respectively. The final
      cryoprotectant concentrations were 11% glycerol or 6% DMA. Thawed sperm were
      evaluated for plasma membrane integrity and quality, motility, acrosome integrity
      and, after artificial insemination, for egg fertility and hatchability.
      Commercial turkey hens were used for all fertility trials, regardless of semen
      source. Turkey sperm frozen with glycerol exhibited higher membrane integrity and
      membrane quality upon thawing than turkey sperm frozen with DMA although no
      differences in total motility, and only minimal differences in progressive
      motility, were detected among the eight cryopreservation treatments. Within line,
      fertility was affected by cryoprotectant, medium and dilution method, where the
      overall highest percentages of fertile, viable embryos (Day 7) occurred for the
      DMA/ASG/fixed sperm concentration method, while high percentages (15.8-31.5%) of
      fertile, non-viable embryos (Day 1-6) were observed for multiple cryopreservation
      methods, including two glycerol treatments. From a single insemination, the
      duration of true and viable fertility in all lines was 10-13 weeks and 9-10
      weeks, respectively. The duration of hatchability was 4-6 weeks after
      insemination for four of the turkey lines. The highest percentage of viable
      embryos was observed for the commercial line (9.5+/-2.4%), followed by the E line
      (5.3+/-1.3%), F line (3.7+/-2.0%) and RBC2 line (2.6+/-0.8%). For the RBC1 line,
      there was 100% embryonic death by Day 6 of incubation. Overall, better fertility
      results were obtained with the cryoprotectant DMA, the ASG diluent and fixed
      sperm concentration. However, the applicability of this method for preserving
      semen from research populations may be line dependent.

PMID- 24731851
TI  - Spermatozoa from the maned wolf (Chrysocyon brachyurus) display typical canid
      hyper-sensitivity to osmotic and freezing-induced injury, but respond favorably
      to dimethyl sulfoxide.
AB  - We assessed the influences of medium osmolality, cryoprotectant and cooling and
      warming rate on maned wolf (Chrysocyon brachyurus) spermatozoa. Ejaculates were
      exposed to Ham's F10 medium (isotonic control) or to this medium plus NaCl (350
      1000mOsm), sucrose (369 and 479mOsm), 1M glycerol (1086mOsm) or dimethyl
      sulfoxide (Me2SO, 1151mOsm) for 10 min. Each sample then was diluted back into
      Ham's medium and assessed for sperm motility and plasma membrane integrity.
      Although glycerol and Me2SO had no influence (P>0.05), NaCl and sucrose solutions
      affected sperm motility (P<0.05), but not membrane integrity. Motility of sperm
      exposed to <600mOsm NaCl or sucrose was less (P<0.05) than fresh ejaculate, but
      comparable (P>0.05) to the control. As osmolality of the NaCl solution increased,
      motility decreased to <5%. In a separate study, ejaculates were diluted in Test
      Yolk Buffer containing 1M glycerol or Me2SO and cooled from 5 degrees C to -120
      degrees C at -57.8 degrees C, -124.2 degrees C or -67.0 degrees C/min, frozen in
      LN2, thawed in a water bath for 30s at 37 degrees C or 10s at 50 degrees C, and
      then assessed for motility, plasma- and acrosomal membrane integrity.
      Cryopreservation markedly (P<0.05) reduced sperm motility by 70% compared to
      fresh samples. Higher (P<0.05) post-thaw motility (20.0+/-1.9% versus 13.5+/
      2.1%) and membrane integrity (51.2+/-1.7% versus 41.5+/-2.2%) were observed in
      samples cryopreserved in Me2SO than in glycerol. Cooling rates influenced
      survival of sperm cryopreserved in glycerol with -57.8 degrees C/min being
      advantageous (P<0.05). The findings demonstrate that although maned wolf
      spermatozoa are similar to domestic dog sperm in their sensitivity to osmotic
      induced motility damage, the plasma membranes tolerate dehydration, and the cells
      respond favorably to Me2SO as a cryoprotectant.

PMID- 24731853
TI  - Maximising survival: the main concern of women with hereditary breast and ovarian
      cancer who undergo genetic testing for BRCA1/2.
AB  - PURPOSE: Little is known about how women with hereditary breast and/or ovarian
      cancer who test positive for a BRCA gene manage the impact of a positive test
      result on their everyday lives and in the longer term. This study defined the
      experience and needs of women with hereditary breast and ovarian cancer and a
      positive BRCA test over time. METHODS: A grounded theory approach was taken using
      qualitative interviews (n = 49) and reflective diaries. Data collected from
      December 2006 until March 2010 was analysed using the constant comparative
      technique to trace the development of how women manage their concerns of
      inherited cancer. RESULTS: A four stage substantive theory of maximising survival
      was generated that defines the experience of women and how they resolve their
      main concerns. The process of maximising survival begins prior to genetic testing
      in women from high risk families as they expect to get a cancer diagnosis at some
      time. Women with cancer felt they had experienced the worst with a cancer
      diagnosis and altruistically tested for the sake of their children but a positive
      test result temporarily shifted their focus to decision-making around their
      personal health needs. CONCLUSION: This study adds to clinical practice through
      raising awareness and adding insights into how women cope with living with
      inherited cancer risk and the personal and familial ramifications that ensue from
      it. A clear multi-professional structured care pathway for women from genetic
      testing result disclosure to undergoing risk-reducing surgery and/or surveillance
      should be developed.

PMID- 24731852
TI  - Analyzing acute procedural pain in clinical trials.
AB  - Because acute procedural pain tends to increase with procedure time, assessments
      of pain management strategies must take that time relationship into account.
      Statistical time-course analyses are, however, complex and require large patient
      numbers to detect differences. The current study evaluated the abilities of
      various single and simple composite measures such as averaged pain or individual
      patient pain slopes to detect treatment effects. Secondary analyses were
      performed with the data from 3 prospective randomized clinical trials that
      assessed the effect of a self-hypnotic relaxation intervention on procedural
      pain, measured every 10-15 minutes during vascular/renal interventions, breast
      biopsies, and tumor embolizations. Single point-in-time and maximal pain
      comparisons were poor in detecting treatment effects. Linear data sets of
      individual patient slopes yielded the same qualitative results as the more
      complex repeated measures analyses, allowing the use of standard statistical
      approaches (eg, Kruskal-Wallis), and promising analyses of smaller subgroups,
      which otherwise would be underpowered. With nonlinear data, a simple averaged
      score was highly sensitive in detecting differences. Use of these 2 workable and
      relatively simple approaches may be a first step towards facilitating the
      development of data sets that could enable meta-analyses of data from acute pain
      trials.

PMID- 24731854
TI  - The activities of MYC, MNT and the MAX-interactome in lymphocyte proliferation
      and oncogenesis.
AB  - The MYC family of proteins plays essential roles in embryonic development and in
      oncogenesis. Efforts over the past 30 years to define the transcriptional
      activities of MYC and how MYC functions to promote proliferation have produced
      evolving models of MYC function. One picture that has emerged of MYC and its
      partner protein MAX is of a transcription factor complex with a seemingly unique
      ability to stimulate the transcription of genes that are epigenetically poised
      for transcription and to amplify the transcription of actively transcribed genes.
      During lymphocyte activation, MYC is upregulated and stimulates a pro
      proliferative program in part through the upregulation of a wide variety of
      metabolic effector genes that facilitate cell growth and cell cycle progression.
      MYC upregulation simultaneously sensitizes cells to apoptosis and activated
      lymphocytes and lymphoma cells have pro-survival attributes that allow MYC-driven
      proliferation to prevail. For example, the MAX-interacting protein MNT is
      upregulated in activated lymphocytes and was found to protect lymphocytes from
      MYC-dependent apoptosis. Here we review the activities of MYC, MNT and other MAX
      interacting proteins in the setting of T and B cell activation and oncogenesis.
      This article is part of a Special Issue entitled: Myc proteins in cell biology
      and pathology.

PMID- 24731855
TI  - Riboswitches in regulation of Rho-dependent transcription termination.
AB  - Riboswitches are RNA sensors of small metabolites and ions that regulate gene
      expression in response to environmental changes. In bacteria, the riboswitch
      sensor domain usually controls the formation of a strong RNA hairpin that either
      functions as a potent transcription terminator or sequesters a ribosome-binding
      site. A recent study demonstrated a novel mechanism by which a riboswitch
      controls Rho-dependent transcription termination. This riboswitch mechanism is
      likely a widespread mode of gene regulation that determines whether a protein
      effector is able to attenuate transcription. This article is part of a Special
      Issue entitled: Riboswitches.

PMID- 24731856
TI  - A novel acrylamide-free flocculant and its application for sludge dewatering.
AB  - In the present research, copolymers of methyl acrylate (MA) with anionic or
      cationic monomers were synthesized via emulsion polymerization, and used as
      sludge dewatering aids in wastewater treatment. The copolymerization of different
      stoichiometry of two monomers afforded a variety of water soluble copolymers with
      charge densities ranging from 40% to 80%, which align with the charge density of
      current flocculant products. These copolymers resemble current commercial
      products, but provide a greener solution by eliminating acrylamide monomer, which
      is a suspected carcinogen. High molecular weight copolymers were achieved by
      applying powder-like synthesis process with intrinsic viscosity of final products
      as high as 12.98 dl/g for anionic flocculant and 10.74 dl/g for cationic
      flocculant. The copolymers of methyl acrylate and [2
      (Acryloyloxy)ethyl]trimethylammonium chloride (AETAC) with 55% charge density
      exhibited comparable performance in clay settling test, real water jar test, and
      sludge dewatering, when compared to AM-based commercial product in the real
      wastewater treatment application. 

PMID- 24731857
TI  - Nano-structural and compositional basis of devitalized tooth fragility.
AB  - OBJECTIVE: Increased tooth fragility after devitalization is commonly observed
      but there is no definite mechanistic explanation for such phenomenon. Therefore,
      it is important to analyze more profoundly structural and compositional
      properties of this altered form of dentin. The present study investigates the
      differences between normal and devitalized dentin using advanced techniques.
      METHODS: Atomic force microscopic imaging (AFM), energy dispersive X-ray analysis
      (EDX) and micro-Raman spectroscopy were performed on 16 dentin specimens, eight
      vital and eight that underwent root-canal treatment at least two years before
      extraction and had no infection in root canals before or after devitalization.
      RESULTS: The mean size of mineral crystals showed by AFM was larger in
      devitalized than in healthy dentin in the same age category. AFM phase shifts in
      devitalized cases revealed altered mechanical characteristics and suggested
      differences in composition of material between devitalized teeth and healthy
      controls. No significant difference in Ca/P ratio between vital and devitalized
      teeth was found using EDX. However, micro-Raman analyses showed that in
      devitalized teeth, apart from hydroxyapatite, dentin contained significant
      amounts of apatite phases with lower calcium content: octacalcium phosphate,
      dicalcium phosphate dihydrate and tricalcium phosphate. SIGNIFICANCE: Differences
      between vital and devitalized dentin bring new insights into the basis of
      devitalized tooth fragility. Larger mineral crystals could account for decreased
      mechanical strength in devitalized teeth. Moreover, calcium-phosphate phases with
      lower Ca content have lower material strength, and the presence of these phases
      in devitalized teeth may explain their increased fragility.

PMID- 24731858
TI  - Prevascularization of biofunctional calcium phosphate cement for dental and
      craniofacial repairs.
AB  - OBJECTIVES: Calcium phosphate cement (CPC) is promising for dental and
      craniofacial repairs. Vascularization in bone tissue engineering constructs is
      currently a major challenge. The objectives of this study were to investigate the
      prevascularization of macroporous CPC via coculturing human umbilical vein
      endothelial cells (HUVEC) and human osteoblasts (HOB), and determine the effect
      of RGD in CPC on microcapillary formation for the first time. METHODS:
      Macroporous CPC scaffold was prepared using CPC powder, chitosan liquid and gas
      foaming porogen. Chitosan was grafted with Arg-Gly-Asp (RGD) to biofunctionalize
      the CPC. HUVEC and HOB were cocultured on macroporous CPC-RGD and CPC control
      without RGD for up to 42d. The osteogenic and angiogenic differentiation, bone
      matrix mineral synthesis, and formation of microcapillary-like structures were
      measured. RESULTS: RGD-grafting in CPC increased the gene expressions of
      osteogenic and angiogenic differentiation markers than those of CPC control
      without RGD. Cell-synthesized bone mineral content also increased on CPC-RGD,
      compared to CPC control (p<0.05). Immunostaining with endothelial marker showed
      that the amount of microcapillary-like structures on CPC scaffolds increased with
      time. At 42d, the cumulative vessel length for CPC-RGD scaffold was 1.69-fold
      that of CPC control. SEM examination confirmed the morphology of self-assembled
      microcapillary-like structures on CPC scaffolds. SIGNIFICANCE: HUVEC+HOB
      coculture on macroporous CPC scaffold successfully achieved prevascularization.
      RGD incorporation in CPC enhanced osteogenic differentiation, bone mineral
      synthesis, and microcapillary-like structure formation. The novel prevascularized
      CPC-RGD constructs are promising for dental, craniofacial and orthopedic
      applications.

PMID- 24731859
TI  - Treatment and prognostic factors of radiation-associated angiosarcoma (RAAS)
      after primary breast cancer: a systematic review.
AB  - BACKGROUND: Radiation-associated angiosarcoma (RAAS) of the breast is a rare,
      aggressive disease. The incidence is increasing with the prolonged survival of
      women irradiated for primary breast cancer. Surgery is the current treatment of
      choice. Prognosis is poor. This review aims to evaluate all publications on
      primary treatment of RAAS to identify prognostic factors and evaluate treatment
      modalities. METHODS: Databases were searched for articles with published
      individual patient data on prognostic factors, treatment and follow-up of
      patients with RAAS. A regression analysis was performed to test the prognostic
      values of age, interval between primary treatment and RAAS, tumour size and grade
      on the local recurrence-free interval (LRFI) and overall survival (OS). The
      effects of treatment modalities surgery, radiation (with or without hyperthermia)
      and chemotherapy or combinations were evaluated. RESULTS: 74 articles were
      included, representing data on 222 patients. In these patients, the 5-year OS was
      43% and 5-year LRFI was 32%. Tumour size and age were significant prognostic
      factors on LRFI and OS. Of all patients, 68% received surgery alone, 17% surgery
      and reirradiation and 6% surgery with chemotherapy. The remaining 9% received
      primary treatments without surgery. Surgery with radiotherapy had a better 5-year
      LRFI of 57% compared to 34% for surgery alone (p=0.008). The value of other
      treatment modalities could not be assessed. CONCLUSIONS: This systematic review
      confirms the poor prognosis of RAAS. Tumour size and age were of prognostic
      value. The addition of reirradiation to surgery in the treatment of RAAS appears
      to enhance local control.

PMID- 24731860
TI  - Associations of mental illness and substance use disorders with prescription
      contraception use among women veterans.
AB  - OBJECTIVE: To investigate whether mental illness and substance use disorder (SUD)
      are associated with having a prescription contraceptive method among women
      veterans. STUDY DESIGN: We conducted a retrospective analysis of National
      Veterans Administration (VA) administrative and clinical data for women veterans
      aged 18-45 years who made at least one primary care visit in 2008. We assessed
      associations between mental illness (depression, posttraumatic stress disorder,
      anxiety, bipolar disorder, schizophrenia and adjustment disorder) and SUD
      (drug/alcohol use disorder) with having a prescription contraceptive method from
      VA (pill, patch, ring, injection, implant and intrauterine device) using
      multivariable logistic regression with random effects for VA facility, adjusting
      for confounders. RESULTS: Among 94,115 reproductive aged women, 36.5% had mental
      illness only, 0.6% had SUD only, 5.3% had both mental illness and SUD and 57.7%
      had neither diagnosis. In these groups, 22.1%, 14.6%, 18.2% and 17.7% (p<0.001),
      respectively, had documentation in 2008 of prescription contraception. After
      adjusting for potential confounders, women with mental illness only were as
      likely as women with neither diagnosis to have a prescription method and were
      more likely to use a highly effective prescription method (implant or
      intrauterine device) if using contraception [adjusted odds ratio (aOR) 1.17, 95%
      confidence interval (CI) = 1.08-1.27]. Women with SUD (with or without mental
      illness) were significantly less likely to have a prescription method than women
      with neither diagnosis (aOR 0.73, 95% CI = 0.57-0.95 and aOR 0.79, 95% CI = 0.73
      0.86, respectively). CONCLUSION: Women veterans with SUD are less likely to have
      prescription contraception compared to other women, which may increase their risk
      of unintended pregnancy.

PMID- 24731861
TI  - Phase I trials.

PMID- 24731862
TI  - Drugs, populations, and type II diabetes mellitus.

PMID- 24731863
TI  - Race, risk, and behaviors: race and disproportionate burdens of chronic disease.

PMID- 24731864
TI  - Having their say: patients' perspectives and the clinical management of diabetes.
AB  - Using an illness narratives framework, we provide 1 method that health care
      providers can use to obtain insight into the perceptions and experiences of their
      patients living with diabetes. We propose that understanding patients' cultural
      perspectives help explains their health behavior and can lead to more productive
      partnering between provider, patient, and community health resources that support
      adherence and improved health outcomes. We conclude with resources available to
      assist health care providers in their efforts to deliver culturally appropriate
      diabetes care and examples of culturally tailored community-based public health
      initiatives that have been effective in improving diabetes outcomes among African
      American patients. 

PMID- 24731865
TI  - Glucometer use and glycemic control among Hispanic patients with diabetes in
      southern Florida.
AB  - BACKGROUND: Self-monitoring of blood glucose (SMBG) has been deemed a critical
      component of diabetes care in the United States. To be effective, patients must
      have some diabetes knowledge, glucometer proficiency, and an ability to take
      appropriate actions when certain readings are obtained. However, most patients
      take no action in response to out-of-range glucometer readings, and in many
      populations, SMBG practices are not associated with improved glycemic control.
      Thus, SMBG utilization is being reconsidered in other countries. Nonetheless,
      SMBG behaviors are increasingly recommended in the United States, where the
      Hispanic population represents the fastest-growing minority group and is
      disproportionately affected by suboptimal diabetes outcomes. Because a growing
      number of interventions aim to reduce diabetes disparities by improving glycemic
      control among minorities, it is essential to determine whether efforts should
      focus on SMBG practices. We present data on SMBG behaviors and glycemic control
      among participants from the Miami Healthy Heart Initiative (MHHI), a National
      Institutes of Health/National Heart, Lung, and Blood Institute-sponsored trial
      assessing a community health worker (CHW) intervention among Hispanic patients
      with poorly controlled diabetes. OBJECTIVE: This study examined the effects of a
      CHW intervention on SMBG practices, glycosylated hemoglobin (HbA1c), and
      knowledge of appropriate responses to glucometer readings among Hispanic patients
      with diabetes. METHODS: This study was an ancillary investigation within MHHI, a
      randomized, controlled trial in 300 Hispanic patients. Participants were
      intervention-group members who received 12 months of CHW support. Assessments
      were administered at baseline and poststudy to determine potential barriers to
      optimal health. Items from validated instruments were used to determine knowledge
      of appropriate responses to different glucose readings. These data were linked to
      HbA1c values. Means and frequencies were used to describe population
      characteristics and glucometer proficiency. Paired-sample t tests examined
      potential differences in HbA1c outcomes and SMBG practices. Qualitative data were
      collected from the CHWs who worked with study participants. RESULTS: Our
      population was diverse, representing several countries. Mean HbA1c improved
      significantly, from 10% to 8.8% (P <= 0.001). SMBG practices did not change. At
      baseline, 96% of patients reported owning a glucometer and 94% reported knowing
      how to use it. However, quantitative assessments and qualitative data suggested
      that participants had suboptimal knowledge regarding actions that could cause an
      out-of-range reading or how to respond to certain readings. CONCLUSIONS: SMBG
      behaviors were not associated with glycemic control in our sample. We conclude
      that a CHW intervention may improve glycemic control without improving SMBG
      practices. Future interventions may reconsider whether efforts should be directed
      toward improving SMBG behaviors.

PMID- 24731866
TI  - Age at onset determines severity and choice of treatment in early rheumatoid
      arthritis: a prospective study.
AB  - INTRODUCTION: Disease activity, severity and comorbidity contribute to increased
      mortality in patients with rheumatoid arthritis (RA). We evaluated the impact of
      age at disease onset on prognostic risk factors and treatment in patients with
      early disease. METHODS: In this study, 950 RA patients were followed regularly
      from the time of inclusion (<12 months from symptom onset) for disease activity
      (erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), tender and/or
      swollen joints, Visual Analogue Scale pain and global scores, and Disease
      Activity Score in 28 joints (DAS28)) and function (Health Assessment
      Questionnaire (HAQ)). Disease severity, measured on the basis of radiographs of
      the hands and feet (erosions based on Larsen score), extraarticular disease,
      nodules, and comorbidities and treatment (disease-modifying antirheumatic drugs
      (DMARDs), corticosteroids, biologics and nonsteroidal anti-inflammatory drugs)
      were recorded at the time of inclusion and at 5 years. Autoantibodies (rheumatoid
      factor, antinuclear antibodies and antibodies against cyclic citrullinated
      peptides (ACPAs)) and genetic markers (human leucocyte antibody (HLA) shared
      epitope and protein tyrosine phosphatase nonreceptor type 22 (PTPN22)) were
      analysed at the time of inclusion. Data were stratified as young-onset RA (YORA)
      and late-onset RA (LORA), which were defined as being below or above the median
      age at the time of onset of RA (58 years). RESULTS: LORA was associated with
      lower frequency of ACPA (P < 0.05) and carriage of PTPN22-T variant (P < 0.01),
      but with greater disease activity at the time of inclusion measured on the basis
      of ESR (P < 0.001), CRP (P < 0.01) and accumulated disease activity (area under
      the curve for DAS28 score) at 6 months (P < 0.01), 12 months (P < 0.01) and 24
      months (P < 0.05), as well as a higher HAQ score (P < 0.01) compared with YORA
      patients. At baseline and 24 months, LORA was more often associated with erosions
      (P < 0.01 for both) and higher Larsen scores (P < 0.001 for both). LORA was more
      often treated with corticosteroids (P < 0.01) and less often with methotrexate (P
      < 0.001) and biologics (P < 0.001). YORA was more often associated with early
      DMARD treatment (P < 0.001). The results of multiple regression analyses
      supported our findings regarding the impact of age on chosen treatment.
      CONCLUSION: YORA patients were more frequently ACPA-positive than LORA patients.
      LORA was more often associated with erosions, higher Larsen scores, higher
      disease activity and higher HAQ scores at baseline. Nevertheless, YORA was
      treated earlier with DMARDs, whilst LORA was more often treated with
      corticosteroids and less often with DMARDs in early-stage disease. These findings
      could have implications for the development of comorbidities.

PMID- 24731868
TI  - Characterization of an aphid-specific, cysteine-rich protein enriched in salivary
      glands.
AB  - Aphids secrete saliva into the phloem during their infestation of plants.
      Previous studies have identified numerous saliva proteins, but little is known
      about the characteristics (physical and chemical) and functions of these proteins
      in aphid-plant interactions. This study characterized an unknown protein
      (ACYPI39568) that was predicted to be enriched in the salivary glands of pea
      aphid. This protein belongs to an aphid-specific, cysteine-rich protein family
      that contains 14 conserved cysteines. ACYPI39568 is a monomeric globular protein
      with a high beta strand extent. The binding stoichiometric ratios for Zn(2+) and
      ACYPI39568 were approximately 3:1 and 1:1 at two binding sites. ACYPI39568 was
      predominantly expressed in the first instar stage and in the salivary glands.
      Aphids required more ACYPI39568 when feeding on plants than when feeding on an
      artificial diet. However, the interference of ACYPI39568 expression did not
      affect the survival rate of aphids on plants. 

PMID- 24731867
TI  - Antihypertensive and neuroprotective effects of catestatin in spontaneously
      hypertensive rats: interaction with GABAergic transmission in amygdala and
      brainstem.
AB  - The chromogranin A-derived peptide catestatin (CST) exerts sympathoexcitatory and
      hypertensive effects when microinjected into the rostral ventrolateral medulla
      (RVLM: excitatory output); it exhibits sympathoinhibitory and antihypertensive
      effects when microinjected into the caudal ventrolateral medulla (CVLM:
      inhibitory output) of vagotomized normotensive rats. Here, continuous infusion of
      CST into the central amygdalar nucleus (CeA) of spontaneously hypertensive rats
      (SHRs) for 15 days resulted in a marked decrease of blood pressure (BP) in 6
      month- (by 37 mm Hg) and 9-month- (by 65 mm Hg)old rats. Whole-cell patch-clamp
      recordings on pyramidal CeA neurons revealed that CST increased both spontaneous
      inhibitory postsynaptic current (sIPSC) amplitude plus frequency, along with
      reductions of sIPSC rise time and decay time. Inhibition of GABAA receptors
      (GABAARs) by bicuculline completely abolished CST-induced sIPSC, corroborating
      that CST signals occur through this major neuroreceptor complex. Hypertension is
      a major risk factor for cerebrovascular diseases, leading to vascular dementia
      and neurodegeneration. We found a marked neurodegeneration in the amygdala and
      brainstem of 9-month-old SHRs, while CST and the GABAAR agonist Muscimol provided
      significant neuroprotection. Enhanced phosphorylation of Akt and ERK accounted
      for these neuroprotective effects through anti-inflammatory and anti-apoptotic
      activities. Overall our results point to CST exerting potent antihypertensive and
      neuroprotective effects plausibly via a GABAergic output, which constitute a
      novel therapeutic measure to correct defects in blood flow control in disorders
      such as stroke and Alzheimer's disease.

PMID- 24731869
TI  - Developmental biology.

PMID- 24731870
TI  - Reply to "Letter to the Editor" by Serisier regarding "effectiveness and safety
      of macrolides in bronchiectasis patients: a meta-analysis and systematic review".

PMID- 24731871
TI  - The important implications of particulate substrate in determining the
      physicochemical characteristics of extracellular polymeric substances (EPS) in
      activated sludge.
AB  - Since the notable amount of particulate substrate in wastewater, the implications
      of particulate substrate on treatment efficiency have been a topic of major
      interest in the field of biological wastewater treatment. The particulate
      substrate has to be hydrolyzed by the extracellular enzymes, which are mainly
      embedded in extracellular polymeric substances (EPS) matrix of microbial
      aggregates, prior to consumption. Therefore, the important relevance between the
      particulate substrate and the characteristics of EPS can be expected. In this
      study, two lab-scale sequencing batch reactors were performed in parallel to
      investigate the effects of particulate and soluble substrate on the
      physicochemical characteristics of EPS in activated sludge. The results showed
      that the particulate substrate in the influent could significantly change the
      properties of activated sludge and the characteristics of EPS. More open and
      fluffy flocs with poorer settleability and dewaterability were formed with
      particulate substrate. More protein and humic compounds were introduced into the
      EPS matrix due to the deep involvement of protein and humic compounds in
      hydrolysis process of particulate substrate. The increments of protein and humic
      compounds then caused the slight higher molecular weight, higher hydrophobicity
      and lower zeta potential of EPS in particulate substrate system. The results in
      this study permitted for obtaining answers to understand the significant
      implications of particulate substrate in determining the physicochemical
      characteristics of EPS in biological wastewater treatment systems. 

PMID- 24731872
TI  - Crude glycerol as feedstock for polyhydroxyalkanoates production by mixed
      microbial cultures.
AB  - The increase in global biodiesel production makes imperative the development of
      sustainable processes for the use of its main by-product, crude glycerol. In this
      study the feasibility of polyhydroxyalkanoates (PHA) production by a mixed
      microbial community using crude glycerol as feedstock was investigated. The
      selected culture had the ability to consume both glycerol and methanol fraction
      present in the crude. However, glycerol seemed to be the only carbon source
      contributing for the two biopolymers stored: poly-3-hydroxybutyrate (PHB) and
      glucose biopolymer (GB). In this work the culture reached a maximum PHB content
      of 47% (cdw) and a productivity of 0.27 g X/L.d, with an aerobic mixed cultures
      and a real waste substrate with non-volatile fatty acids (VFA) organic matter.
      The overall PHA yield on total substrate obtained was in the middle range of
      those reported in literature. The fact that crude glycerol can be used to produce
      PHA without any pre-treatment step, makes the overall production process
      economically more competitive, reducing polymer final cost. 

PMID- 24731873
TI  - Bio-reduction of tetrachloroethen using a H2-based membrane biofilm reactor and
      community fingerprinting.
AB  - Chlorinated ethenes in drinking water could be reductively dechlorinated to non
      toxic ethene by using a hydrogen based membrane biofilm reactor (H2-MBfR) under
      denitrifying conditions as it provides an appropriate environment for
      dechlorinating bacteria in biofilm communities. This study evaluates the
      reductive dechlorination of perchloroethene (PCE) to non-toxic ethene (ETH) and
      comparative community analysis of the biofilm grown on the gas permeable membrane
      fibers. For these purposes, three H2-MBfRs receiving three different chlorinated
      ethenes (PCE, TCE and DCE) were operated under different hydraulic retention
      times (HRTs) and H2 pressures. Among these reactors, the H2-MBfR fed with PCE (H2
      MBfR 1) accomplished a complete dechlorination, whereas cis-DCE accumulated in
      the TCE receiving H2-MBfR 2 and no dechlorination was detected in the DCE
      receiving H2-MBfR 3. The results showed that 95% of PCE dechlorinated to ETH
      together with over 99.8% dechlorination efficiency. Nitrate was the preferred
      electron acceptor as the most of electrons generated from H2 oxidation used for
      denitrification and dechlorination started under nitrate deficient conditions at
      increased H2 pressures. PCR-DGGE analysis showed that Dehalococcoides were
      present in autotrophic biofilm community dechlorinating PCE to ethene, and RDase
      genes analysis revealed that pceA, tceA, bvcA and vcrA, responsible for complete
      dechlorination step, were available in Dehalococcoides strains. 

PMID- 24731875
TI  - Electronic cigarettes: navigating the vapor.

PMID- 24731874
TI  - Biological treatment and thickening with a hollow fibre membrane bioreactor.
AB  - Aerobic operation of an immersed hollow fibre membrane bioreactor, treating
      municipal wastewater supplemented with molasses solution, has been studied across
      mixed liquor suspended solids (MLSS) concentrations between 8 and 32 g L(-1), the
      higher concentrations being normally associated with thickening operations. Only
      a marginal loss in membrane permeability was noted between 8 and 18 g L(-1) when
      operation was conducted without clogging. The sustainable operational flux
      attainable above 18 g L(-1) was highly dependent upon both the MLSS concentration
      and the state of the membrane. A temperature-corrected flux of 28 L m(-2) h(-1)
      (LMH) was sustained for 18 h at an MLSS of 8 g L(-1) using membranes close to
      initial their virgin-state permeability. This value decreased to around 14 LMH at
      20 g L(-1) and 5 LMH at 32 g L(-1) MLSS for an aged membrane whose permeability
      had been recovered following clogging. Below the threshold flux operation without
      significant clogging was possible, such that the membrane permeability could be
      recovered with a chemically enhanced backflush (CEB). Above this flux clogging
      took place at a rate of around 7-14 g solids per m(2) membrane per m(3) permeate
      volume passed irrespective of the MLSS concentration. The permeability of the
      unclogged membrane was depressed and could not be recovered using a standard CEB,
      indicative of irrecoverable pore clogging. The outcomes corroborated previously
      reported observations concerning the deleterious long-term impacts of clogging,
      and confirmed the critical importance of operation at a sustainable flux value. 

PMID- 24731876
TI  - Multitasking capacities in persons diagnosed with schizophrenia: a preliminary
      examination of their neurocognitive underpinnings and ability to predict real
      world functioning.
AB  - Difficulties in everyday life activities are core features of persons diagnosed
      with schizophrenia and in particular during multitasking activities. However, at
      present, patients' multitasking capacities have not been adequately examined in
      the literature due to the absence of suitable assessment strategies. We thus
      recently developed a computerized real-life activity task designed to take into
      account the complex and multitasking nature of certain everyday life activities
      where participants are required to prepare a room for a meeting. Twenty-one
      individuals diagnosed with schizophrenia and 20 matched healthy controls
      completed the computerized task. Patients were also evaluated with a cognitive
      battery, measures of symptomatology and real world functioning. To examine the
      ecological validity, 14 other patients were recruited and were given the
      computerized version and a real version of the meeting preparation task. Results
      showed that performance on the computerized task was significantly correlated
      with executive functioning, pointing to the major implication of these cognitive
      processes in multitasking situations. Performance on the computerized task also
      significantly predicted up to 50% of real world functioning. Moreover, the
      computerized task demonstrated good ecological validity. These findings suggest
      the importance of evaluating multitasking capacities in patients diagnosed with
      schizophrenia in order to predict real world functioning. 

PMID- 24731877
TI  - Contributions of peripheral, spinal, and supraspinal actions to analgesia.
AB  - Pain signaling involves several main compartments that can be considered as
      potential sites for analgesic drug actions. When drugs are given systemically,
      they can act at spinal, supraspinal and peripheral sites, and several methods
      have been developed for identifying where they act. These include (1) localized
      delivery of drugs to specific sites (via intracerebral, intrathecal, and
      intraplantar injections), (2) systemic delivery of drugs with localized delivery
      of antagonists for the receptor on which the drug acts or for a system recruited
      by the drug, (3) use of peripherally restricted analogs, and (4) use of
      conditional knockout technology to selectively deplete receptors on nociceptors.
      Delivery of drugs simultaneously to several sites (spinal/supraspinal,
      peripheral/spinal, and peripheral/supraspinal) reveals "self-synergy" between
      sites for some agents. Knowledge of peripheral contributions to drug actions is
      important because of the potential to develop peripherally restricted analgesics
      (with a diminished side effect profile due to not entering the central nervous
      system), the potential to deliver drugs peripherally (e.g. topically) to act on
      sensory nerve endings and adjacent tissue (with a diminished side effect profile
      due to limited systemic absorption), and the potential to use combinations of
      topical and oral drug regimens to obtain improved pain relief (without increasing
      the side effect burden). This review considers methods used for compartmental
      analysis, and results of such site analysis for several major classes of
      analgesic drugs that are in current use. 

PMID- 24731878
TI  - Effect of glyphosate-based herbicide on early life stages of Java medaka (Oryzias
      javanicus): a potential tropical test fish.
AB  - Glyphosate is globally a widely used herbicide, yet there is little information
      on their toxicity to marine fishes. Java medaka, a small tropical fish native to
      coastal areas in several Southeast Asian countries, is viewed as a suitable
      candidate for toxicity test and thus was used for this study. Java medaka adults
      were cultured in the laboratory and the fertilized eggs of the F2 generation were
      exposed to different concentrations of glyphosate-based herbicide (100, 200, 300,
      400 and 500 ppm) until they hatched. The survival and hatching rates of the
      embryos, changes in the heart rate and morphological impairments were recorded.
      Generally, survival and hatching percentage decreased as glyphosate concentration
      increased. Absence of pectoral fin(s) and cornea, permanently bent tail,
      irregular shaped abdomen, and cell disruption in the fin, head and abdomen are
      among the common teratogenic effects observed. Furthermore, risk factor also
      increased with the increased in glyphosate concentrations.

PMID- 24731879
TI  - Optimization of dispersive liquid-liquid microextraction for preconcentration and
      spectrophotometric determination of phenols in Chabahar Bay seawater after
      derivatization with 4-aminoantipyrine.
AB  - We have optimized dispersive liquid-liquid microextraction to preconcentrate
      trace phenolic compounds after derivatization with 4-aminoantipyrine in
      artificial sea water for spectrophotometric determination. Factors such as
      reaction time (7.5 min), pH (9.5), solvent (chloroform), dispersing solvent
      (ethanol), and volume ratio of dispersing to organic phase (11:1) were optimized.
      Under optimum conditions, the limit of detection was 0.18 MUg/L and the linearity
      range 1-900 MUg/L. The relative standard deviation and enrichment factor were 6%
      (n=7) and 920, respectively. The results demonstrate the efficiency of coupling
      the 5530 APHA standard for derivation and dispersive liquid-liquid
      microextraction of phenolic compounds from seawater samples. Using this method,
      total phenol content in seawater from several locations in Chabahar Bay
      (southeast Iran) was estimated at 27.8-74.8 MUg/L.

PMID- 24731880
TI  - The roles of flowering, overwinter survival and sea surface temperature in the
      long-term population dynamics of Zostera marina around the Isles of Scilly, UK.
AB  - Interaction between biotic and abiotic drivers of dynamics is an important topic
      in ecology. Despite numerous short-term studies, there is a paucity of evidence
      about how environmental structure modifies dynamics in marine systems. We
      quantified Zostera marina flowering and non-flowering shoot density annually from
      1996 to 2012 around the Isles of Scilly, UK, parameterizing a population dynamic
      model. Flowering is structured in time and space, with temperature and flowering
      positively associated at some locations only. We found no evidence that flower
      production contributes to seagrass density but 'patchiness' was positively
      associated with flowering in the previous year. With evidence of substantial
      overwinter survival, findings support the hypothesis that local populations are
      maintained largely through vegetative reproduction but sexual reproduction may
      contribute to colonisation of vacant habitat. This long-term study (1) tests
      validity of shorter-term investigations, (2) quantifies interaction between
      biotic and abiotic factors and (3) promotes seagrass as a model ecosystem. 

PMID- 24731881
TI  - Epidemic characteristics of hand, foot, and mouth disease in southern China,
      2013: coxsackievirus A6 has emerged as the predominant causative agent.

PMID- 24731882
TI  - Hypertension and intracranial aneurysms: association or causation?

PMID- 24731883
TI  - High and low or dorsal and ventral?

PMID- 24731884
TI  - In search for the core of apraxia.

PMID- 24731885
TI  - The growing burden of cancer in India: epidemiology and social context.
AB  - Cancer can have profound social and economic consequences for people in India,
      often leading to family impoverishment and societal inequity. Reported age
      adjusted incidence rates for cancer are still quite low in the demographically
      young country. Slightly more than 1 million new cases of cancer are diagnosed
      every year in a population of 1.2 billion. In age-adjusted terms this represents
      a combined male and female incidence of about a quarter of that recorded in
      western Europe. However, an estimated 600,000-700,000 deaths in India were caused
      by cancer in 2012. In age-standardised terms this figure is close to the
      mortality burden seen in high-income countries. Such figures are partly
      indicative of low rates of early-stage detection and poor treatment outcomes.
      Many cancer cases in India are associated with tobacco use, infections, and other
      avoidable causes. Social factors, especially inequalities, are major determinants
      of India's cancer burden, with poorer people more likely to die from cancer
      before the age of 70 years than those who are more affluent. In this first of
      three papers, we examine the complex epidemiology of cancer, the future burden,
      and the dominant sociopolitical themes relating to cancer in India.

PMID- 24731886
TI  - Cancer prevention and care in India: an unfinished agenda.

PMID- 24731887
TI  - Cancer research in India: national priorities, global results.
AB  - Over the past 20 years, cancer research in India has grown in size and impact.
      Clinicians, scientists, and government and state policy makers in India have
      championed cancer research, from studies to achieve low-tech, large-scale health
      outcomes to some of the most advanced areas of fundamental cancer science. In
      this paper, we frame public policy discussions about cancer with use of an in
      depth analysis of research publications from India. Cancer research in India is a
      complex environment that needs to balance public policy across many competing
      agendas. We identify major needs across these environments such as those for
      increased research capacity and training and protected time for clinical
      researchers; for more support from states and enhanced collaborative funding
      programmes from government; for development of national infrastructures across a
      range of domains (ie, clinical trials, tissue banking, registries, etc); and for
      a streamlined and rational regulatory environment. We also discuss improvements
      that should be made to translate research into improvements in cancer outcomes
      and public health. 

PMID- 24731888
TI  - Delivery of affordable and equitable cancer care in India.
AB  - The delivery of affordable and equitable cancer care is one of India's greatest
      public health challenges. Public expenditure on cancer in India remains below
      US$10 per person (compared with more than US$100 per person in high-income
      countries), and overall public expenditure on health care is still only slightly
      above 1% of gross domestic product. Out-of-pocket payments, which account for
      more than three-quarters of cancer expenditures in India, are one of the greatest
      threats to patients and families, and a cancer diagnosis is increasingly
      responsible for catastrophic expenditures that negatively affect not only the
      patient but also the welfare and education of several generations of their
      family. We explore the complex nature of cancer care systems across India, from
      state to government levels, and address the crucial issues of infrastructure,
      manpower shortages, and the pressing need to develop cross-state solutions to
      prevention and early detection of cancer, in addition to governance of the
      largely unregulated private sector and the cost of new technologies and drugs. We
      discuss the role of public insurance schemes, the need to develop new political
      mandates and authority to set priorities, the necessity to greatly improve the
      quality of care, and the drive to understand and deliver cost-effective cancer
      care programmes. 

PMID- 24731889
TI  - Do placebo effects associated with sham osteopathic procedure occur in newborns?
      Results of a randomized controlled trial.
AB  - BACKGROUND: Placebo effect has been largely studied and debated in medicine.
      Research focused mainly on children and adults but not on newborns. In
      osteopathy, few studies documented this effect and no research has been conducted
      in newborns. OBJECTIVES: To assess the presence of placebo effect in newborns
      using sham osteopathic manipulative treatment. DESIGN: Randomized control trial.
      SETTING: Neonatal Intensive Care Unit in Italy. INTERVENTIONS: Two groups (103
      patients each) of preterm infants aged 29-36 weeks without medical complications
      received routine pediatric care and osteopathic sham therapy was administrated to
      the study group only for the entire period of hospitalization. MAIN OUTCOME
      MEASURES: Primary end point was the mean reduction of length of stay at
      discharge. Secondary objective was the change in daily weight gain. RESULTS: 206
      newborns entered the study. No difference between sham and control group was
      found for the primary outcome length of stay (30.0+/-20.3; 28.8+/-18.9; p=0.70).
      Multivariate analysis showed no difference between study and control group on
      length of stay. A negative association was found for gestational age (-2.33; 95%
      CI -3.81 to -0.85; p=0.002), birth weight (-0.01; 95% CI -0.02 to -0.01; p<0.001)
      and milk volume at study enrollment (-0.02; 95% CI -0.05 to -0.01; p=0.01).
      CONCLUSIONS: To the best of our knowledge, this study is the first in the field
      showing no placebo effect on newborns. Further discussions are opened concerning
      the age when placebo effect starts.

PMID- 24731890
TI  - A randomized controlled trial of the effects of a stress management programme
      during pregnancy.
AB  - BACKGROUND: Prenatal maternal stress is associated with adverse birth outcomes.
      Relaxation techniques might be effective in reducing stress during that period.
      The purpose of this study was to evaluate the effects of applied relaxation in
      reducing anxiety and stress in pregnant women in their second trimester, as well
      as raising their sense of control. Also we expected to see a difference in some
      lifestyle factors associated with stress. A randomized control trial with a
      prospective pretest-posttest experimental design was used. METHODS: Sixty
      primigravida women in their second trimester were assigned randomly to receive a
      6-week stress management programme (N=31) (relaxation breathing and progressive
      muscle relaxation, RB-PMR, twice a day) or not (N=29). Self-reported validated
      measures were used to evaluate perceived stress, health locus of control and
      anxiety at baseline and at the end of the 6-weeks follow-up. RESULTS: The results
      of the study demonstrated significant benefits from the use of the techniques in
      the psychological state of the pregnant women. The systematic implementation of
      the proposed relaxation techniques contributed in the reduction of perceived
      stress (mean change -3.23, 95% CI: -4.29 to -0.29) and increased the sense of
      control (mean change 1.99, 95% CI: 0.02-3.7). CONCLUSION: The findings suggest
      beneficial effects of relaxation on reducing perceived stress as well as
      increment of sense of control in pregnant women. The results of this study
      support the claim that training in the proposed relaxation techniques may
      constitute an ideal, non-pharmaceutical, intervention that can promote well
      being, at least during pregnancy. Longer studies will be necessary in the future,
      in order to examine the long-term effects of relaxation techniques.

PMID- 24731891
TI  - Effect of lavender inhalation on the symptoms of primary dysmenorrhea and the
      amount of menstrual bleeding: A randomized clinical trial.
AB  - OBJECTIVE: The purpose of this study was to explore the effect of Lavandula
      angustifolia (lavender) inhalation on the symptoms of dysmenorrhea and the amount
      of menstrual bleeding in female students with primary dysmenorrhea. DESIGN: This
      study is an experimental clinical trial. The subjects were 96 female students
      residing in dormitory at Tehran University of Medical Sciences in 2011 and
      suffering from level two or three dysmenorrhea according to the verbal multi
      dimensional scoring system. The inclusion criteria were as: being single,
      suffering from primary dysmenorrhea, having no genital organs disorder, having no
      systemic disease, having regular menstrual cycles, using no contraceptives, etc.
      The follow-up time was 4 menstrual cycles. INTERVENTIONS: The subjects were
      randomized into two groups: experimental (n=48) who inhaled lavender based on
      sesame oil, and placebo (n=48) who inhaled sesame oil only. MAIN OUTCOME
      MEASURES: The severity of dysmenorrhea symptoms was measured through a
      questionnaire, and the amount of menstrual bleeding was measured by sanitary
      towel usage. METHODS: Ordinal logistic regression and generalized estimating
      equation (GEE) were used to analyze the data. RESULTS: The symptoms of
      dysmenorrhea were significantly lowered in the lavender group compared to the
      placebo group (p<0.001). The amount of menstrual bleeding in the lavender group
      was reduced in comparison to the placebo group but the difference was not
      statistically significant (p=0.25). No significant difference was observed for
      blood clot among the students (p=0.666). CONCLUSIONS: This study showed that
      lavender inhalation was effective in alleviating dysmenorrhea symptoms,
      suggesting that it could be applied by midwives in a safe manner because of no
      side effects, simplicity and cost-effectiveness for all patients.

PMID- 24731892
TI  - The effect of olive oil and the Saj(r) cream in prevention of striae gravidarum:
      A randomized controlled clinical trial.
AB  - OBJECTIVE: To compare the clinical efficacy of olive oil and the Saj((r)) cream
      on the occurrence and severity of striae gravidarum. DESIGN: Parallel randomized
      controlled clinical trial. SETTING: West Health Centre, Lolagar and Akbarabadi
      Hospitals, Tehran, Iran. INTERVENTIONS: 360 Nulliparous women at their second
      trimester of pregnancy randomly (simple randomization) allocated into three
      groups of olive oil, the Saj((r)) cream, and control that finally 150 of them (50
      subjects in each group) completed the study. Control group did not receive any
      medication/intervention. At gestational age of 38-40 weeks the participants were
      evaluated regarding the occurrence of striae on abdominal skin and its severity
      that were primary outcome of the study. RESULTS: In the olive oil group, striae
      occurred in 72% of the participants, which were mild, moderate, and severe in
      32%, 26%, and 6% of the cases, respectively. In those who received Saj((r))
      cream, striae occurred in 64% of the cases, which were mild, moderate and severe
      in 16%, 34%, and 14% of the cases, respectively. With regard to the control
      group, striae occurred in 60% of the participants, among which striae were mild,
      moderate, and severe in 22%, 24%, and 14% of the cases, respectively. There were
      no statistically significant differences among the three studied groups regarding
      the incidence or severity of striae. CONCLUSION: Neither olive oil nor the
      Saj((r)) cream were effective in preventing the occurrence of striae gravidarum
      or affecting its severity. Further studies to examine the effect of other
      herbal/chemical preparations on occurrence of striae gravidarum are recommended.

PMID- 24731893
TI  - Effects of yoga practice on stress-related symptoms in the aftermath of an
      earthquake: A community-based controlled trial.
AB  - OBJECTIVES: To evaluate the effect of an integrated hatha yoga practice on
      perceived stress and stress-related symptoms in the aftermath of an earthquake.
      DESIGN AND SETTING: Inhabitants, aged 20-67 years, from highly exposed earthquake
      areas of two villages in South Iceland were offered to participate in a yoga
      program subsequent to an earthquake. Sixty-six individuals were self-selected
      into the study and divided by residential convenience into an experimental group
      (n=31) and a waiting list control group (n=35). INTERVENTION: The yoga program
      was conducted twice a week for six weeks, in normal situations among the
      inhabitants in the community. MAIN OUTCOME MEASURES: Several validated
      questionnaires assessing stress and stress-related symptoms, posttraumatic
      symptoms, depression, anxiety and health related quality of life were
      administered at pre- and post-intervention. RESULTS: Multivariate analysis of
      variance (MANOVA) revealed differences between the experimental group and waiting
      list control group on sleep quality (p=.03) and social relations (p=.04). These
      differences did not prevail at Bonferroni correction for multiple testing (at
      alpha level of .005). Participants in both groups showed significant improvements
      in stress and some stress-related symptoms such as sleep, concentration, well
      being, quality of life, depression and anxiety from pre- to post-intervention.
      CONCLUSIONS: The data from this small study show no statistically significant
      improvement of an integrated hatha yoga program above and beyond waiting list
      control, following exposure to an earthquake. However, the observed trend toward
      improved sleep quality and social relations deserve further exploration in larger
      effectiveness studies on the impact of Hatha yoga on recovery after natural
      disaster.

PMID- 24731894
TI  - Core muscle function during specific yoga poses.
AB  - OBJECTIVE: To assess the potential use of 11 yoga poses in specific training and
      rehabilitation programs via examination of the muscle activation patterns in
      selected trunk and hip muscles. DESIGN: Repeated-measures descriptive study.
      SETTING: University laboratory, US. PARTICIPANTS: Thirty healthy yoga
      practitioners with more than 3 months yoga practice experience (mean age+/-SD,
      32.0+/-12.3 y; 8 M/22 F) participated. INTERVENTIONS: Surface electromyographic
      signals of upper rectus abdominis, lower rectus abdominis, longissimus thoracis,
      external oblique abdominis and gluteus maximum muscle were recorded in 11 yoga
      poses: Halfway lift, Forward fold, Downward facing dog, Upward facing dog, High
      plank, Low plank, Chair, Mountain with arms down, Mountain with arms up, Warrior
      1 (both sides). MAIN OUTCOME MEASURES: Root mean square values of each muscle
      during each pose, normalized by the maximal voluntary contraction. RESULTS: There
      were significant main effects of pose (p<.001) and muscle (p<.001), and a
      significant pose*muscle interaction (p=.001). The post hoc analysis revealed
      unique patterns for the five muscles of interest for each of the 11 poses
      (p<.024). CONCLUSIONS: Variations in core muscle firing patterns depend on the
      trunk and pelvic positions during these poses. Training programs can be developed
      by choosing particular poses to target specific core muscles for addressing low
      back pain and declines in performance. The High plank, Low plank and Downward
      facing dog poses are effective for strengthening external oblique abdominis,
      Chair and Warrior 1 poses for targeting gluteus maximum, and Chair and Halfway
      lift poses for strengthening longissimus thoracis. And these three muscles could
      be strengthened by the Upward facing dog pose.

PMID- 24731895
TI  - Effect of qigong training on fatigue in haemodialysis patients: A non-randomized
      controlled trial.
AB  - BACKGROUND: Fatigue is a debilitating symptom in haemodialysis patients. Qigong
      presents a potentially safe modality of treatment for chronic fatigue patients
      but has not yet been evaluated in haemodialysis patients. OBJECTIVE: The aim of
      this study is to investigate whether qigong exercise affects fatigue in
      haemodialysis patients. DESIGN: A 6-month non-randomized control trial with six
      measurement periods was conducted. The qigong group was taught to practice qigong
      three times per week for six months. The control group received usual routine
      care. Main outcome measure Fatigue, as measured by the "Haemodialysis Patients
      Fatigue Scale". RESULTS: A total of 172 patients participated in this study, with
      71 patients in the qigong group and 101 patients in the control group. The
      results indicated that all patients experienced mild to moderate fatigue. There
      was no difference between the qigong and control groups in fatigue at baseline.
      However, fatigue was lower in the qigong group than in the control group at 8
      weeks (43.5 vs. 53.9), 12 weeks (44.7 vs. 53.6), 16 weeks (43.2 vs. 50.8), 20
      weeks (42 vs. 50.2), and 24 weeks (41.4 vs. 48.4). The results, based on the
      generalized estimating equation method, showed that fatigue was significantly
      lower in the qigong group than in the control group (odds ratio=0.004, p=0.005).
      CONCLUSION: Fatigue in the qigong group showed a continuous decrease, which was
      maintained until the end of data collection at 24 weeks. Thus, qigong presents a
      potentially effective and safe method to reduce fatigue in haemodialysis
      patients.

PMID- 24731896
TI  - Intra-operative music listening for anxiety, the BIS index, and the vital signs
      of patients undergoing regional anesthesia.
AB  - OBJECTIVE: The aim of this study was to investigate the effects of intraoperative
      music listening on anxiety, the BIS index, and the vital signs of patients
      undergoing regional anesthesia in an operating room. METHODS: Eighty patients who
      were scheduled for a surgery that would use regional anesthesia were allocated to
      either the music therapy group listened to music using headphones for the entire
      surgery or no-treatment control group. Outcome measures were blood pressure (BP)
      and the BIS index. RESULTS: Anxiety was significantly differed between the two
      groups (t=11.27, p=<.001). The BIS index was significantly lower in the
      experimental group than the control group from 15min to the end of the operation
      (F=7.25, p<.001). Vital signs marginally differed between the two groups.
      CONCLUSION: Music therapy during surgery maybe an effective nursing intervention
      that relieves anxiety and increases sedation in patients undergoing surgery with
      regional anesthesia.

PMID- 24731897
TI  - Traditional Chinese medicine for idiopathic precocious puberty: A hospital-based
      retrospective observational study.
AB  - OBJECTIVES: To characterize the application of traditional Chinese medicine (TCM)
      among children with idiopathic precocious puberty (IPP). DESIGN AND SETTING: This
      study examined data sets from patients diagnosed with IPP at Chang Gung Memorial
      Hospital between 2010 and 2012. The patients were allocated into three groups
      according their voluntary choice of treatment modalities: TCM users (received TCM
      treatment only), Western medicine (WM) users (received WM treatment only), and
      "no treatment" group (received no medical treatment at all). MAIN OUTCOME
      MEASURES: The demographic data of children with IPP were characterized. The
      prescription patterns and frequencies of TCM for IPP patients were analyzed. The
      patients' bone maturation rates and the change of predicted height after
      different approaches were measured as outcomes. RESULTS: There were 3390 patients
      enrolled in the study. Zhi-Bai-Di-Huang-Wan (70.62%) was the most common herbal
      formula and Mai-Ya (Hordei Fructus Germinatus) (51.58%) was the most common
      single herb prescribed for IPP in all of the 2784 prescriptions. The bone
      maturation rates of TCM users (0.95+/-0.20) and WM users (0.69+/-0.05) were both
      decelerated but the "no treatment" group had an accelerated bone maturation rate
      of 1.33+/-0.04. TCM and WM users also had higher predicted height after treatment
      (1.15+/-1.19cm versus 1.73+/-0.29cm), while the "no treatment" group had a
      decreased predicted height (-0.52+/-0.23cm). CONCLUSIONS: Our study revealed a
      comprehensive list of TCM prescriptions for IPP patients. Future well-designed,
      randomized, double-blinded, and placebo-controlled clinical trials are warranted
      to evaluate the efficacy and safety of TCM for precocity.

PMID- 24731898
TI  - Complementary effects of auricular acupressure in relieving constipation symptoms
      and promoting disease-specific health-related quality of life: A randomized
      placebo-controlled trial.
AB  - OBJECTIVES: Constipation has been identified as a worldwide health problem among
      elderly people. Currently, it is not effectively relieved by the use of laxatives
      and lifestyle modification. Previous studies reported promising results in
      managing constipation with auricular acupressure (AA), although its effectiveness
      was not affirmed. This study is to evaluate the complementary effects of AA in
      relieving constipation symptoms and in promoting disease-specific health-related
      quality of life (HRQOL) among elderly residential care home (RCH) residents in
      Hong Kong. DESIGN: Randomized placebo-controlled trial. SETTING: Elderly RCH.
      INTERVENTION: Ninety-nine participants were randomly assigned to either
      experimental group (AA using auricular plasters with magnetic pellets), placebo
      controlled group (AA using auricular plasters with Semen Vaccariae), or usual
      care group (AA using auricular plasters only). AA was applied onto seven
      auricular acupoints for 10 days. MAIN OUTCOME MEASURES: Constipation symptoms and
      disease-specific HRQOL were measured before AA, at the completion of AA (D10),
      and at the 10th-day follow-up time (D20). RESULTS: Significant group*time
      interaction effect was found in the change of satisfaction subscale between the
      experimental group and placebo-controlled group at D10 (p=0.016) and D20
      (p=0.016) relative to the baselines. For both constipation symptoms and disease
      specific HRQOL, the experimental group demonstrated the greatest improvement
      after receiving AA at both D10 and D20 compared with the other two groups.
      CONCLUSION: The current findings indicated positive clinical value of AA with
      magnetic pellets in managing constipation in elderly RCH residents. AA was also
      found to be a safe and acceptable intervention.

PMID- 24731899
TI  - Mindfulness-based cognitive therapy for the treatment of headache pain: A mixed
      methods analysis comparing treatment responders and treatment non-responders.
AB  - OBJECTIVES: Our recent pilot study demonstrated mindfulness-based cognitive
      therapy (MBCT) is a potentially efficacious headache pain treatment; however, it
      was not universally effective for all participants. This study sought to explore
      patient characteristics associated with MBCT treatment response and the potential
      processes of change that allowed treatment responders to improve and that were
      potentially lacking in the non-responders. DESIGN: We implemented a mixed-methods
      analysis of quantitative and qualitative data. The sample consisted of 21
      participants, 14 of whom were classified as treatment responders (>=50%
      improvement in pain intensity and/or pain interference) and seven as non
      responders (<50% improvement). SETTING: The study was conducted at the Kilgo
      Headache Clinic and the University of Alabama Psychology Clinic. INTERVENTION:
      Participants completed an 8-week MBCT treatment for headache pain management.
      MEASURES: Standardized measures of pain, psychosocial outcomes, and non-specific
      therapy factors were obtained; all participants completed a post-treatment semi
      structured interview. RESULTS: Quantitative data indicated a large effect size
      difference between responders and non-responders for pre- to post-treatment
      change in standardized measures of pain acceptance and catastrophizing, and a
      small to medium effect size differences on treatment dose indicators. Both groups
      showed improved psychosocial outcomes. Qualitatively, change in cognitive
      processes was a more salient qualitative theme within treatment responders; both
      groups commented on the importance of non-specific therapeutic factors. Barriers
      to mindfulness meditation were also commented on by participants across groups.
      CONCLUSIONS: Results indicated that change in pain related cognitions during an
      MBCT intervention for headache pain is a key factor underlying treatment
      response.

PMID- 24731900
TI  - Evidence-based practice in chiropractic practice: A survey of chiropractors'
      knowledge, skills, use of research literature and barriers to the use of research
      evidence.
AB  - BACKGROUND: Scant research has been undertaken regarding chiropractors' skills
      and knowledge associated with evidence-based practice (EBP), and their perceived
      barriers to EBP. These issues appear to have been examined in only one small
      qualitative study and one small study of chiropractors holding orthopaedic
      diplomas. The lack of research in this area suggests that additional studies are
      warranted to develop a better understanding of factors that affect chiropractors'
      use of research evidence in clinical practice. METHODS: We used a modified online
      questionnaire that captured information regarding EBP skills and knowledge, and
      barriers to EBP. Its adaption was informed by the use of a content validity
      panel. The questionnaire was disseminated through email by Australian
      chiropractic professional organisations and the Chiropractic Board of Australia.
      Logistic regression analyses were conducted to examine univariate associations
      between responses to items measuring knowledge and skills with items measuring:
      age; years since registration; reading research literature; and use of research
      literature in clinical decision-making. RESULTS: 584 respondents returned
      questionnaires. About half of the respondents stated they had learned the
      foundations of EBP (56.6%) during their undergraduate training. Slightly more
      than two thirds of the respondents were confident in their ability to critically
      review literature (69.5%) and find relevant research to answer clinical questions
      (72.6%). The most common factors involved with reading more research, and
      increased use of research literature in clinical decision-making, were confidence
      in critical appraisal skills and confidence in finding relevant research
      literature. Conclusion Educational interventions should be implemented to enhance
      Australian chiropractors' fundamental EBP skills.

PMID- 24731901
TI  - Using a questionnaire among patient, resident doctor and senior supervisor: Are
      their answers the same?
AB  - OBJECTIVES: This study aims to contribute to the development of objective
      diagnostic standards in Traditional Chinese Medicine (TCM), in order to improve
      the training of physicians. METHODS: We devised a questionnaire study to evaluate
      the accuracy of resident doctors' diagnostic skills by comparing their assessment
      of patients with those of their senior supervising physician and the patients
      themselves. We selected 39 patients with systemic lupus erythematosus (SLE) at
      Chang Gung Memorial Hospital, Taiwan, between November 1, 2008 and June 30, 2012,
      and had the resident doctors (R), their senior supervisor (S) and their patients
      (P) fill out questionnaires before treatment (V1), immediately after treatment
      (V5) and two months after treatment (V6), in order to record their assessments on
      the patients' condition. The R and S questionnaires covered subjective symptoms,
      tongue, and pulse, while the P questionnaires only included general symptoms. We
      then compared the assessment records to determine the level of agreement between
      them. RESULTS: The agreements of inquiry during the study for P and S were 0.78
      (V1) to 0.84 (V6) and 0.87 (V1) to 0.94 (V6) for R and S, respectively, the
      agreements between R and S for tongue diagnosis and pulse diagnosis were 0.87
      (V1) to 0.90 (V6) and 0.91 (V1) to 0.95 (V6), respectively. All the above
      agreements improved with time from V1 to V6. CONCLUSIONS: The results show that
      the patient input was feasible and effective and that the questionnaire method
      provided an objective assessment standard to determine how successfully the
      resident doctor was trained. Furthermore, it facilitated a training process that
      could help resident doctors improve their skills.

PMID- 24731902
TI  - Asking patients the right questions about herbal and dietary supplements: Cross
      cultural perspectives.
AB  - BACKGROUND: Use of dietary supplements (DS) during hospitalization carries risks
      such as reducing drug treatment efficacy and increasing peri-operative
      complications due to DS-drug interactions and DS side effects. In this study, we
      aimed to develop socio-cultural-sensitive patient histories to detect DS use
      amongst hospitalized patients from different backgrounds. RESEARCH DESIGN AND
      METHODS: Prospective cohort study of hospitalized patients from June 2009 through
      March 2010, using mixed quantitative (questionnaires), and qualitative (semi
      structured interviews) research methodology to detect DS use. RESULTS: Data were
      provided by 691 of 895 patients (response rate 77.2%). Of these, 359 (51.9%)
      reported using DS in the previous year. 168 (46.8%) disclosed DS use following a
      standard question on DS consumption. 191 (53.2%) respondents disclosed DS use
      only following further questioning utilizing DS-related keywords. Leading
      questioning techniques that facilitated admitting DS use included: naming common
      DS (50.6% disclosure rate), and using traditional/herbal medicine (THM) related
      keywords (41.3% disclosure rate) such as infusions, teas, herbs picked in the
      garden. A logistic multivariate regression model indicated that disclosure of DS
      use, by using THM related keywords was associated with non-Jewish religion
      [EXP(B)=3.57, 95% C.I. 1.70-7.50, p=0.001], dwelling in rural areas (p=0.004),
      and having a lower degree of education (p=0.01). CONCLUSIONS: Improved history
      taking regarding DS use in hospitalized patients can be accomplished by using
      specific keywords that address socio-cultural diversities as in the following
      question: "Do you use any natural, folk, traditional, grandma remedies, herbs
      picked in the garden, infusions or herbal teas to improve your health?.

PMID- 24731903
TI  - Single and triple moxibustion with large, indirect moxa induced differential
      effects on skin temperature and blood perfusion in healthy human subjects:
      Counterevidence to a previous report.
AB  - OBJECTIVES: This study aims to investigate the possible differences in skin
      temperature and blood perfusion changes between single and triple moxibustion.
      DESIGN AND SETTING: Thirty healthy volunteers were randomly divided into two
      groups: a triple moxibustion group (n=15) received indirect moxibustion on CV12
      for 30min and a single moxibustion group (n=15) for 10min. After 10min of bed
      rest, skin temperature and blood perfusion were measured by digital infrared
      thermal imaging and laser Doppler perfusion imaging eight times in total, pre
      moxibustion and 0, 5, 10, 15, 20, 25 and 30min post moxibustion. MAIN OUTCOME
      MEASUREMENT: The changes in the skin temperature and blood perfusion in an area
      5cm in diameter around CV12 at 0min post treatment compared to baseline was the
      main outcome measurement. RESULTS: The difference of changes in skin temperature
      and blood perfusion on CV12 between the two groups remained statistically
      significant for 30min in an area 5cm in diameter around CV12 and for 25min in a
      15-cm-diameter area. No adverse events were reported. CONCLUSION: Triple
      moxibustion with large, indirect moxa appeared to induce greater increases in
      skin temperature and blood perfusion than single moxibustion.

PMID- 24731904
TI  - Additive homeopathy in cancer patients: Retrospective survival data from a
      homeopathic outpatient unit at the Medical University of Vienna.
AB  - BACKGROUND: Current literature suggests a positive influence of additive
      classical homeopathy on global health and well-being in cancer patients. Besides
      encouraging case reports, there is little if any research on long-term survival
      of patients who obtain homeopathic care during cancer treatment. DESIGN: Data
      from cancer patients who had undergone homeopathic treatment complementary to
      conventional anti-cancer treatment at the Outpatient Unit for Homeopathy in
      Malignant Diseases, Medical University Vienna, Department of Medicine I, Vienna,
      Austria, were collected, described and a retrospective subgroup-analysis with
      regard to survival time was performed. Patient inclusion criteria were at least
      three homeopathic consultations, fatal prognosis of disease, quantitative and
      qualitative description of patient characteristics, and survival time. RESULTS:
      In four years, a total of 538 patients were recorded to have visited the
      Outpatient Unit Homeopathy in Malignant Diseases, Medical University Vienna,
      Department of Medicine I, Vienna, Austria. 62.8% of them were women, and nearly
      20% had breast cancer. From the 53.7% (n=287) who had undergone at least three
      homeopathic consultations within four years, 18.7% (n=54) fulfilled inclusion
      criteria for survival analysis. The surveyed neoplasms were glioblastoma, lung,
      cholangiocellular and pancreatic carcinomas, metastasized sarcoma, and renal cell
      carcinoma. Median overall survival was compared to expert expectations of
      survival outcomes by specific cancer type and was prolonged across observed
      cancer entities (p<0.001). CONCLUSION: Extended survival time in this sample of
      cancer patients with fatal prognosis but additive homeopathic treatment is
      interesting. However, findings are based on a small sample, and with only limited
      data available about patient and treatment characteristics. The relationship
      between homeopathic treatment and survival time requires prospective
      investigation in larger samples possibly using matched-pair control analysis or
      randomized trials.

PMID- 24731905
TI  - Droplet evaporation method as a new potential approach for highlighting the
      effectiveness of ultra high dilutions.
AB  - OBJECTIVE: This study sought to verify whether the droplet evaporation method
      (DEM) can be applied to assess the effectiveness of ultra-high dilutions (UHDs).
      We studied the shape characteristics of the polycrystalline structures formed
      during droplet evaporation of wheat seed leakages. METHODS: The experimental
      protocol tested both unstressed seeds and seeds stressed with arsenic trioxide
      5mM, treated with either ultra-high dilutions of the same stressor substance, or
      with water as a control. The experimental groups were analyzed by DEM and in
      vitro growth tests. DEM patterns were evaluated for their local connected fractal
      dimension (measure of complexity) and fluctuating asymmetry (measure of symmetry
      exactness). RESULTS: Treatment with arsenic at UHD of both stressed and non
      stressed seeds increased the local connected fractal dimension levels and
      bilateral symmetry exactness values in the polycrystalline structures, as
      compared to the water treatment. The results of in vitro growth tests revealed a
      stimulating effect of arsenic at UHD vs. control, and a correlation between the
      changes in growth rate and the crystallographic values of the polycrystalline
      structures was observed. CONCLUSIONS: The results indicate that polycrystalline
      structures are sensitive to UHDs, and so for the first time provide grounds for
      the use of DEM as a new tool for testing UHD effectiveness. DEM could find
      application as a treatment pre-selection tool, or to monitor sample conditions
      during treatment. Moreover, when applied to biological liquids (such as saliva,
      blood, blood serum, etc.), DEM might provide information about UHD effectiveness
      on human and animal health.

PMID- 24731906
TI  - Diabetes with pyogenic liver abscess--A perspective on tongue assessment in
      traditional Chinese medicine.
AB  - BACKGROUND: This novel study provides a time series analysis of tongue features
      extracted from a diabetic patient with pyogenic liver abscess (PLA), treated with
      the integration of western medicine and traditional Chinese medicine (TCM). The
      features, namely, tongue color, tongue fur thickness and fur color, identified
      from a series of tongue images taken every two days, exhibit significant
      transitions matching closely with the progression of disease. These tongue
      features could serve as effective, non-intrusive indices for different
      progression stages of diabetes with PLA. CASE PRESENTATION: A 76-year-old male
      diabetic patient was admitted for hyperglycemic hyperosmolar state. Intermittent
      fever and abdominal discomfort were noted. After performing abdominal computed
      tomography and laboratory studies, the results indicated pyeogenic liver abscess,
      Klebsiella pneumoniae ssp. pneumoniae related. As PLA progressed, the patient
      suffered spiking fever and right upper abdominal pain. Tongue examination
      revealed features with red tongue, white-yellow and thick fur. After receiving
      pigtail catheter drainage, the fever subsided and the pus-like fluid was drained
      smoothly. During the course of this process, gradually dwindled tongue fur
      witnessed through periodic tongue examination coincides consistently with
      laboratory data, namely, body temperature, fasting plasma glucose and plasma
      glucose level gathered. CONCLUSION: This is the first time series analysis of
      applying tongue examination to the progression of a specific disease. Through a
      series of tongue images taken periodically, tongue color, tongue fur thickness
      and fur color are identified to closely linked to the progression of diabetes
      with PLA, as indicated by data gathered through means of plasma glucose and
      abdominal sonographic follow-ups. Based on this promising finding, our future
      study will further extend the application of tongue assessment to evaluate the
      tongue characteristics of diabetic patients.

PMID- 24731907
TI  - What "CAM" we learn about the level of evidence from 60 years of research into
      manipulative and body-based therapies in sports and exercise medicine?
AB  - OVERVIEW: Complementary and alternative medicine (CAM) is becoming increasingly
      accepted in modern western society, including amongst amateur and professional
      athletes, however, it has not yet been determined how CAM is reflected in
      scientific publications in sports and exercise medicine (SEM). AIM: The aim of
      this study was to identify trends in the levels of evidence for manipulative and
      body-based therapies within the SEM literature. METHODS: The literature was
      systematically searched with no language restrictions in seven databases and
      retrieved articles were screened and classified according to their study design
      using the Oxford Centre for Evidence-Based Medicine system. RESULTS: From 6088
      retrieved articles, 395 were retained for evaluation and these included 180 on
      massage, 96 on acupuncture and 95 on manipulation. The majority of the articles
      were published in English, with 88 in non-English languages. Level-1 evidence was
      available for acupuncture, manipulation, massage, and Pilates. From the nineteen
      seventies onwards, a decreasing trend was observed for low evidence articles with
      a corresponding increasing trend for clinical trials. After the year 2000, over
      50% of the published articles were clinical trials, RCTs or systematic reviews.
      CONCLUSIONS: This review revealed an increase in the quantity and quality of
      published manipulative and body-based therapy articles in SEM over the last 60
      years with the evidence level varying considerably between therapies. The
      timeframe associated with the development of evidence in CAM may reflect the move
      to provide scientific support for therapies previously justified primarily by
      anecdotal evidence, or traditional and cultural use.

PMID- 24731908
TI  - Safflower yellow for acute ischemic stroke: A systematic review of randomized
      controlled trials.
AB  - OBJECTIVES: Stroke is one of the most common causes of mortality worldwide.
      Safflower yellow is widely used for the treatment of acute ischemic stroke in
      China. Several trials comparing safflower yellow and placebo or no intervention
      were unavailable for prior meta-analysis. Here, we present an updated and
      expanded systematic review, including four new trials, to evaluate the efficacy
      and safety of safflower yellow for the treatment of acute ischemic stroke.
      METHODS: A comprehensive search was performed in Cochrane Central Register of
      Controlled Trials (CENTRAL), Medline, Embase, the Allied and Complementary
      Medicine Database (AMED), China National Knowledge Infrastructure (CNKI), China
      Biological Medicine Database (CBM), CQVIP Information and Wanfang Database until
      January 2013. Only randomized controlled trials (RCTs) evaluating the efficacy
      and safety of safflower yellow for acute ischemic stroke were included. Two
      researchers (Fan, S.Y. and Lin, N.) independently extracted data, assessed the
      study quality, and selected trials for inclusion. RESULTS: 7 RCTs with 762
      participants were included. None of the included studies were of high
      methodological quality. The meta-analysis showed that safflower yellow was more
      effective assessed by neurological improvement rate [odds ratio (OR), 3.11; 95%
      confidence interval (CI) 2.06-4.68, P<0.05] compared with control group. No death
      was reported in any of the included studies during the follow up period. Only
      four trials reported adverse events, and skin rash was observed in the treatment
      group of one trial. CONCLUSIONS: Safflower yellow seems to be effective and safe
      in the treatment of acute ischemic stroke. However, RCTs of high methodological
      quality are warranted before drawing any conclusion on the efficacy or safety of
      safflower yellow for acute ischemic stroke.

PMID- 24731909
TI  - Meta-analysis of Chinese herbal Xiaoyao formula as an adjuvant treatment in
      relieving depression in Chinese patients.
AB  - BACKGROUND: Chinese herbal Xiaoyao formula (XYF) has been widely used as an
      adjuvant treatment for depression in China. The objective of this meta-analysis
      was to assess the efficacy and safety of XYF in relieving depression in Chinese
      patients. METHODS: Systematic literature searches were carried out on the Pubmed,
      Embase, Cochrane Library, China National Knowledge Infrastructure, and Wanfang
      database (prior to June 2013). Only randomized controlled trials (RCTs) comparing
      XYF plus antidepressants with antidepressants alone for patients with depression
      were selected. The main outcomes were changes in weighted mean difference (WMD)
      and 95% confidence interval (CI) of the Hamilton depression scale (HAMD) and risk
      ratios (RRs) and 95% CI for adverse events. RESULTS: Ten RCTs involving 735
      patients were identified and analyzed. All of the included RCTs were associated
      with a moderate to high risk of bias. In the meta-analysis, XYF plus
      antidepressants reduced the HAMD scores compared with antidepressants alone (WMD 
      2.15; 95% CI -3.56 to -0.74) in a random effect model. In subgroup analysis, XYF
      plus antidepressants reduced WMD was not observed in the treatment duration less
      than 8 weeks' subgroup (WMD -1.37; 95% CI -2.92 to 0.19) and XYF powder subgroup
      (WMD -2.87; 95% CI -7.40 to 1.66). The adverse events included hyperhidrosis, dry
      mouth, nausea, and constipation. No serious adverse events were reported in any
      of the included trials. CONCLUSIONS: XYF as an adjuvant treatment appeared to
      have benefits on depressive patients. In addition, XYP appeared to reduce
      insomnia and constipation related to antidepressants.

PMID- 24731910
TI  - Effectiveness of animal-assisted therapy: A systematic review of randomized
      controlled trials.
AB  - The objectives of this review were to summarize the evidence from randomized
      controlled trials (RCTs) on the effects of animal-assisted therapy (AAT). Studies
      were eligible if they were RCTs. Studies included one treatment group in which
      AAT was applied. We searched the following databases from 1990 up to October 31,
      2012: MEDLINE via PubMed, CINAHL, Web of Science, Ichushi Web, GHL, WPRIM, and
      PsycINFO. We also searched all Cochrane Database up to October 31, 2012. Eleven
      RCTs were identified, and seven studies were about "Mental and behavioral
      disorders". Types of animal intervention were dog, cat, dolphin, bird, cow,
      rabbit, ferret, and guinea pig. The RCTs conducted have been of relatively low
      quality. We could not perform meta-analysis because of heterogeneity. In a study
      environment limited to the people who like animals, AAT may be an effective
      treatment for mental and behavioral disorders such as depression, schizophrenia,
      and alcohol/drug addictions, and is based on a holistic approach through
      interaction with animals in nature. To most effectively assess the potential
      benefits for AAT, it will be important for further research to utilize and
      describe (1) RCT methodology when appropriate, (2) reasons for non-participation,
      (3) intervention dose, (4) adverse effects and withdrawals, and (5) cost. 

PMID- 24731911
TI  - Chinese patent medicine Xuefu Zhuyu capsule for the treatment of unstable angina
      pectoris: A systematic review of randomized controlled trials.
AB  - BACKGROUND: Xuefu Zhuyu Capsule (XFZY) has been commonly used for relieving chest
      pain in patients with coronary heart disease (CHD). Randomized controlled trials
      (RCTs) on XFZY in treating unstable angina (UA) have not been systematically
      reviewed. OBJECTIVE: This study aims to provide a PRISMA-compliant systematic
      review to evaluate the efficacy of XFZY in treating UA. METHODS: An extensive
      search of 7 medical databases was performed up to June 2013. RCTs involving XFZY
      or combined with conventional drugs versus conventional drugs were identified.
      Meta-analysis was performed to evaluate the cardiovascular effects of XFZY. Rev
      Man 5.0 was used for data analysis. RESULTS: 8 RCTs were included in this review.
      Statistical analysis of the results showed that XFZY combined with conventional
      drugs had significant effect on relieving angina symptoms (RR: 1.26 [1.16, 1.38];
      P<0.00001) and improving ECG (RR: 1.20 [1.04, 1.38]; P=0.01) compared with
      conventional drugs alone. No severe adverse events were reported. CONCLUSIONS:
      XFZY combined with conventional drugs appears to have potential cardiovascular
      effects in treatment of UA with few adverse events. However, further rigorous
      designed trials are still needed.

PMID- 24731912
TI  - Using the theory of planned behavior to explore attitudes and beliefs about
      dietary supplements among HIV-positive Black women.
AB  - BACKGROUND: This cross-sectional study investigated whether the theory of planned
      behavior (TPB) constructs: attitudes, subjective norms, and perceived behavioral
      control were related to intention of dietary supplements use among African
      American women living with Human Immunodeficiency Virus and/or Acquired Immune
      Deficiency Syndrome (HIV/AIDS). METHODS: A closed-ended questionnaire based on
      the TPB was utilized to explore the use of dietary supplements among a cohort of
      153 HIV-positive African-American women. RESULTS: Overall, 45% of the respondents
      used dietary supplements to manage/control their HIV. Combined, attitudes,
      subjective norms and perceived behavioral control were significant predictors of
      intention toward dietary supplement use (69% of the variance explained,
      p<0.0001). Attitudes (beta=0.23, p<0.001) and perceived behavioral control
      (beta=0.45, p<0.0001) were found to be significant independent predictors of
      intention. Behavioral intention and proximal TPB constructs (attitudes,
      subjective norms, and perceived behavioral control), as well as their underlying
      beliefs about dietary supplements use, were all found to be significantly more
      positive in users of dietary supplements compared to non-users (p<0.001).
      CONCLUSIONS: Results showed that attitudes, subjective norms and perceived
      behavioral control are important predictors in the intention to use dietary
      supplements for control of HIV among African-American women. Implications from
      this study suggest that the TPB can be used to better identify and understand
      salient beliefs that surround intentions to use alternative therapies for
      management of disease. These beliefs can be used to develop interventions
      surrounding HIV treatment and care.

PMID- 24731913
TI  - Analyzing the research in Integrative & Complementary Medicine by means of
      science mapping.
AB  - OBJECTIVES: The research in the Complementary and Alternative Medicine (CAM)
      field is analyzed according to the journals indexed in ISI Web of Science.
      Science Mapping Analysis (SMA) is used to provide and overview of the conceptual
      evolution of the CAM field. METHODS: The software SciMAT is used to detect and
      visualize the hidden themes and their evolution over a consecutive span of years.
      It combines SMA and performance analysis. Twenty one journals related to CAM were
      analyzed, in four consecutive periods from 1974 to 2011. RESULTS: Strategic
      diagrams and the thematic evolution of CAM, together with performance indicators
      (h-index), were obtained. The results show that CAM research has focused on seven
      main thematic areas: MEDICINAL-PLANTS, CHIROPRACTIC-AND-LOW-BACK-PAIN,
      ACUPUNCTURE-AND-PAIN, CELL-PROCESSES-AND-DISEASES, LIPID-PEROXIDATION and
      DIABETES-AND-INSULIN. CONCLUSION: The research output could be used by the
      scientific community to identify thematic areas on which interest is focused.

PMID- 24731914
TI  - Development and validation of TOF-SIMS and CLSM imaging method for cytotoxicity
      study of ZnO nanoparticles in HaCaT cells.
AB  - Zinc oxide nanoparticles (ZnO NPs) exhibit novel physiochemical properties and
      have found increasing use in sunscreen products and cosmetics. The potential
      toxicity is of increasing concern due to their close association with human skin.
      A time-of-flight secondary ion mass spectrometry (TOF-SIMS) and confocal laser
      scanning microscopy (CLSM) imaging method was developed and validated for rapid
      and sensitive cytotoxicity study of ZnO NPs using human skin equivalent HaCaT
      cells as a model system. Assorted material, chemical, and toxicological analysis
      methods were used to confirm their shape, size, crystalline structure, and
      aggregation properties as well as dissolution behavior and effect on HaCaT cell
      viability in the presence of various concentrations of ZnO NPs in aqueous media.
      Comparative and correlative analyses of aforementioned results with TOF-SIMS and
      CLSM imaging results exhibit reasonable and acceptable outcome. A marked drop in
      survival rate was observed with 50MUg/ml ZnO NPs. The CLSM images reveal the
      absorption and localization of ZnO NPs in cytoplasm and nuclei. The TOF-SIMS
      images demonstrate elevated levels of intracellular ZnO concentration and
      associated Zn concentration-dependent (40)Ca/(39)K ratio, presumably caused by
      the dissolution behavior of ZnO NPs. Additional validation by using stable
      isotope-labeled (68)ZnO NPs as tracers under the same experimental conditions
      yields similar cytotoxicity effect. The imaging results demonstrate spatially
      resolved cytotoxicity relationship between intracellular ZnO NPs, (40)Ca/(39)K
      ratio, phosphocholine fragments, and glutathione fragments. The trend of change
      in TOF-SIMS spectra and images of ZnO NPs treated HaCaT cells demonstrate the
      possible mode of actions by ZnO NP involves cell membrane disruption, cytotoxic
      response, and ROS mediated apoptosis. 

PMID- 24731915
TI  - Enhancement of cell production in photosynthetic bacteria wastewater treatment by
      low-strength ultrasound.
AB  - The present study is aimed at enhanced cell production in together with pollution
      removal in photosynthetic bacteria wastewater treatment through low-strength
      ultrasound stimulation. The ultrasound strength was 0.3W/cm(2) with 40kHz
      frequency. Results showed 1-10min sonication significantly improved the cell
      production. The optimal sonication time was 2min. When the irradiation period was
      over 10min, a strong mechanical damage occurred. These phenomena could be
      explained by the changes of PSB dehydrogenase activity. Sonication stimulated the
      initial dehydrogenase activity; moderate sonication increased the cell activity
      while too-long sonication led to quick enzyme activity decrease. The optimal
      sonication strategy was 1min at the 0th hour and 1min at the 27th hour. The
      corresponding cell production and cell yield increased by 110% and 93%
      respectively, and the COD removal reached 98%. The cost of low-strength
      ultrasound was only 1% of the incremental sales value of cells. 

PMID- 24731916
TI  - Nutrient removal and lipid accumulation properties of newly isolated microalgal
      strains.
AB  - In this work, four microalgae including Chlorella sp. SDEC-10, Chlorella
      ellipsoidea SDEC-11, Scenedesmus bijuga SDEC-12 and Scenedesmus quadricauda SEDC
      13 isolated from a local lake have been investigated for the properties of
      growth, nutrient removal and lipid accumulation in synthetic sewage. Their
      biomass ranged between 0.4 and 0.5g/L. The total phosphorus removal efficiency of
      four strains was nearly 100%, but in the case of total nitrogen and ammonium the
      removal efficiency was relatively low. Their lipid content, ranging from 25.92%
      to 27.76% and corresponding to the lipid productivity 7.88-18.08mg/L/d, was
      higher than that obtained in BG-11. Palmitic acid and oleic acid were the
      predominant compositions found through fatty acids analysis. S. quadricauda SDEC
      13 performed best both in nutrient removal and in lipid production among the four
      strains. 

PMID- 24731917
TI  - Effects of an exercise and hypocaloric healthy eating intervention on indices of
      psychological health status, hypothalamic-pituitary-adrenal axis regulation and
      immune function after early-stage breast cancer: a randomised controlled trial.
AB  - INTRODUCTION: Many women experience emotional distress, depression and anxiety
      after a diagnosis of breast cancer. Psychological stress and depression have been
      associated with hypothalamic-pituitary-adrenal (HPA) axis dysregulation that may
      adversely affect immune system functioning and impact upon survival. This study
      investigated the effects of a lifestyle intervention on indices of psychological
      health status, HPA axis regulation and immune function in overweight women
      recovering from early-stage breast cancer treatment. METHODS: A total of 85 women
      treated for breast cancer 3 to 18 months previously were randomly allocated to a
      6-month exercise and hypocaloric healthy eating program plus usual care or usual
      care alone (control group). Women in the intervention group received three
      supervised exercise sessions per week and individualized dietary advice,
      supplemented by weekly nutrition seminars. Depressive symptoms (Beck Depression
      Inventory version II: BDI-II), perceived stress (Perceived Stress Scale: PSS),
      salivary diurnal cortisol rhythms; inflammatory cytokines (IL-6 and Tumor
      necrosis factor-alpha), leukocyte phenotype counts, natural killer (NK) cell
      cytotoxicity and lymphocyte proliferation following mitogenic stimulation were
      assessed at baseline and 6-month follow up. RESULTS: Compared with the control
      group, the intervention group exhibited a reduction in depressive symptoms
      (adjusted mean difference, 95% confidence intervals (95% CI): -3.12, -1.03 to 
      5.26; P = 0.004) at the 6-month follow-up but no significant decrease in PSS
      scores (-2.07, -4.96 to 0.82; P = 0.16). The lifestyle intervention also had a
      significant impact on diurnal salivary cortisol rhythm compared with usual care
      alone, as evidenced by an increase in morning salivary cortisol at the 6-month
      follow-up (P <0.04), indicating a change in HPA axis regulation. Women in the
      control group had higher total leukocyte, neutrophil and lymphocyte counts in
      comparison to the intervention group at the 6-month follow-up (P <=0.05), whereas
      there was no difference in NK cell counts (P = 0.46), NK cell cytotoxicity (P =
      0.85) or lymphocyte proliferation responses (P = 0.11) between the two groups.
      CONCLUSION: Our results show that the lifestyle intervention resulted in a
      reduction in depressive symptoms and a normalisation of HPA axis regulation. Such
      changes could have important implications for long-term survival in women
      recovering from early-breast cancer treatment. TRIAL REGISTRATION: Current
      Controlled Trials: ISRCTN08045231.

PMID- 24731918
TI  - The continued success of registered nurse care coordination in a state evaluation
      of aging in place in senior housing.
AB  - Older adults prefer to age in place, remaining in their home as their health care
      needs intensify. In a state evaluation of aging in place (AIP), the University of
      Missouri Sinclair School of Nursing and Americare System Inc, Sikeston, MO,
      developed an elder housing facility to be an ideal housing environment for older
      adults to test the AIP care delivery model. An evaluation of the first 4 years
      (2005-2008) of the AIP program at TigerPlace (n = 66) revealed that the program
      was effective in restoring health and maintaining independence while being cost
      effective. Similar results evaluating the subsequent 4 years (2009-2012) of the
      program (N = 128) revealed positive health outcomes (fall risk, gait velocity,
      Functional Ambulation Profile, handgrips, Short-Form 12 Physical Health, Short
      Form 12 Mental Health, and Geriatric Depression Scale); slightly negative
      activities of daily living, independent activities of daily living, and Mini
      Mental State Examination; and positive cost-effectiveness results. Combined care
      and housing costs for any resident who was receiving additional care services and
      qualified for nursing home care (n = 44) was about $20,000 less per year per
      person than nursing home care. Importantly, residents continued to live in
      private apartments and were encouraged to be as independent as possible through
      the end of life. 

PMID- 24731919
TI  - The Patient-Centered Outcomes Research Institute (PCORI): information for
      academic nursing.
AB  - As part of the Patient Protection and Affordable Care Act of 2010, the U.S.
      Congress created the Patient-Centered Outcomes Research Institute (PCORI). Its
      goal is to fund research that will assist patients, caregivers, clinicians, and
      others in making informed health decisions. Because nurses play a critical role
      in engaging patients in health care, they are valued participants in setting the
      institute's agenda and carrying out its programs. In this article, we provide an
      overview of PCORI and describe how nurses can participate in institute activities
      and apply for research grants. 

PMID- 24731920
TI  - Where and how is health created?

PMID- 24731921
TI  - Mucopolysaccharidosis: Otolaryngologic findings, obstructive sleep apnea and
      accumulation of glucosaminoglycans in lymphatic tissue of the upper airway.
AB  - OBJECTIVE: The aim of this study is to evaluate otolaryngologic problems (upper
      airway obstruction, obstructive sleep apnea, restriction of mouth opening, middle
      ear effusion, hearing and breathing problems) and their treatments on
      mucopolysaccharidoses (MPS) patients and to investigate accumulation of
      glucosaminoglycans (GAG) in the upper airway biochemically and pathologically.
      METHODS: 76 MPS patients were evaluated. Forty-two MPS patients underwent
      polysomnography (PSG) for obstructive sleep apnea (OSA). Pre- and postoperative
      PSG results of 18 patients were compared. The success and complications of
      treatments for OSA in MPS were evaluated. Biochemical and histopathological
      accumulation of GAG in tonsil and adenoid tissue and middle ear effusion were
      analyzed and compared with the control group. RESULTS: Forty patients out of 42
      tested with PSG had OSA (95%). Adenoid grade, Mallampati grade, restricted mouth
      opening, rate of difficult intubation were significantly different among MPS
      subtypes. MPS types III and IV had significantly lower Mallampati scores; type VI
      had significantly worse mouth opening; and type III had significantly better
      mouth opening and higher rate of easy intubation when compared to other MPS
      types. There was no significant difference between MPS subtypes according to
      tonsil grade, adenoid grade, rate of otitis media with effusion and OSA severity.
      Statistically significant difference was found between GAG accumulation in
      adenoid tissue and middle ear effusion of MPS and control group (p<0.05).
      However, GAG accumulation in tonsil was not significantly different between MPS
      and control group. There was a statistically significant improvement in postop
      Apnea-Hypopnea Index (AHI) compared to preop AHI (p<0.05). CONCLUSIONS: Most MPS
      patients have airway obstruction and OSA due to adenotonsillar hypertrophy. Most
      of these children benefit from adenotonsillectomy, after which OSA significantly
      improves. They experience high recurrence rate after adenoidectomy; though this
      is not clinically problematic. They also suffer from conductive hearing loss due
      to OME, which has to be treated with ventilation tube insertion. However, such
      operations are usually complicated by difficult endotracheal intubation and
      restricted mouth opening. Sometimes tracheotomy may be necessary. Tracheotomy is
      also highly complicated in MPS patients. Significant accumulation of GAG in
      middle ear fluid and adenoid tissue is present; however, GAG appears not to
      accumulate in tonsillar tissue.

PMID- 24731922
TI  - Advanced glycation inhibition and protection against endothelial dysfunction
      induced by coumarins and procyanidins from Mammea neurophylla.
AB  - Advanced glycation end-products (AGEs) are associated with many pathogenic
      disorders such as pathogenesis of diabetes or endothelial dysfunction leading to
      cardiovascular events. Therefore, the identification of new anti-AGE molecules or
      extracts aims at preventing such pathologies. Many Clusiaceae and Calophyllaceae
      species are used in traditional medicines to treat arterial hypertension as well
      as diabetes. Focusing on these plant families, an anti-AGE plant screening
      allowed us to select Mammea neurophylla for further phytochemical and biological
      studies. Indeed, both DCM and MeOH stem bark extracts demonstrated in vitro their
      ability to prevent inflammation in endothelial cells and to reduce
      vasoconstriction. A bioguided fractionation of these extracts allowed us to point
      out 4-phenyl- and 4-(1-acetoxypropyl)coumarins and procyanidins as potent
      inhibitors of AGE formation, potentially preventing endothelial dysfunction. The
      fractionation steps also led to the isolation of two new compounds, namely
      neurophyllols A and B from the DCM bark extract together with thirteen known
      mammea A and E coumarins (mammea A/AA, mammea A/AB, mammea A/BA, mammea A/BB,
      mammea A/AA cycloD, mammea A/AB cycloD, disparinol B, mammea A/AB cycloE,
      ochrocarpin A, mammea A/AA cycloF, mammea A/AB cycloF, mammea E/BA, mammea E/BB)
      as well as delta-tocotrienol, xanthones (1-hydroxy-7-methoxyxanthone, 2
      hydroxyxanthone) and triterpenes (friedelin and betulinic acid). During this
      study, R,S-asperphenamate, previously described from fungal origin was also
      purified. 

PMID- 24731923
TI  - Comparative analysis of innate immune system function in metastatic breast,
      colorectal, and prostate cancer patients with circulating tumor cells.
AB  - In recent years, circulating tumor cells (CTCs) in metastatic cancer patients
      have been found to be a promising biomarker to predict overall survival and tumor
      progression in these patients. A relatively high number of CTCs has been
      correlated with disease progression and poorer prognosis. This study was designed
      to assess innate immune system function, known to be responsible for the immune
      defense against developing neoplasms, in metastatic cancer patients with CTCs.
      Our aim is to provide a link between indication of poorer prognosis, represented
      by the number of CTCs to the cytotoxic activity of natural killer cells, an
      important component of the innate immune system, and to represent a promising
      expanded approach to management of metastatic cancer patients with CTCs. Seventy
      four patients, with metastatic breast, colorectal, or prostate cancer, were
      recruited for this study. Using a flow cytometric assay, we measured natural
      killer (NK) cell cytotoxicity against K562 target cells; and CTCs were enumerated
      using the CellSearch System. Toll-like receptors 2 and 4 expression was also
      determined by flow cytometry. We found that within each of our three metastatic
      cancer patient groups, NK cell cytotoxic activity was decreased in patients with
      a relatively high number of CTCs in peripheral blood compared to patients with a
      relatively low number of CTCs. In the breast and prostate cancer group, patients
      with CTCs greater than 5 had decreased NK cell cytotoxicity when compared to
      patients with less than 5 CTCs. In the colorectal cancer group, we found that 3
      or more CTCs in the blood was the level at which NK cell cytotoxicity is
      diminished. Additionally, we found that the toll-like receptors 2 and 4
      expression was decreased in intensity in all the metastatic cancer patients when
      compared to the healthy controls. Furthermore, within each cancer group, the
      expression of both toll-like receptors was decreased in the patients with
      relatively high number of CTCs, i.e. greater than 5 for the breast and prostate
      cancer group and greater than 3 for the colorectal cancer group, compared to the
      patients with relatively low number, i.e. less than 5 or 3, respectively.
      Treatment options to increase NK cell cytotoxic activity should be considered in
      patients with relatively high numbers of CTCs. 

PMID- 24731924
TI  - Evolutionary conservation of TFIIH subunits: implications for the use of
      zebrafish as a model to study TFIIH function and regulation.
AB  - Transcriptional factor IIH (TFIIH) is involved in cell cycle regulation,
      nucleotide excision repair, and gene transcription. Mutations in three of its
      subunits, XPB, XPD, and TTDA, lead to human recessive genetic disorders such as
      trichothiodystrophy and xeroderma pigmentosum, the latter of which is sometimes
      associated with Cockayne's syndrome. In the present study, we investigate the
      sequence conservation of TFIIH subunits among several teleost fish species and
      compare their characteristics and putative regulation by transcription factors to
      those of human and zebrafish. We report the following findings: (i) comparisons
      among protein sequences revealed a high sequence identity for each TFIIH subunit
      analysed; (ii) among transcription factors identified as putative regulators,
      OCT1 and AP1 have the highest binding-site frequencies in the promoters of TFIIH
      genes, and (iii) TFIIH genes have alternatively spliced isoforms. Finally, we
      compared the protein primary structure in human and zebrafish of XPD and XPB -
      two important ATP-dependent helicases that catalyse the unwinding of the DNA
      duplex at promoters during transcription - highlighting the conservation of
      domain regions such as the helicase domains. Our study suggests that zebrafish, a
      widely used model for many human diseases, could also act as an important model
      to study the function of TFIIH complex in repair and transcription regulation in
      humans. 

PMID- 24731925
TI  - A novel calcium supplement prepared by phytoferritin nanocages protects against
      absorption inhibitors through a unique pathway.
AB  - The consumption of milk is declining in industrialized countries, leading to
      inadequate calcium intake. Therefore, it is important to explore a new class of
      Ca-enriched nutrient for the fortification of food. In this work, we prepared a
      novel class of soluble and edible Ca-protein complexes where approximately 140
      calcium ions were encapsulated within a phytoferritin nanocage. As an alternative
      to other organic and/or inorganic carriers, protein nanocages were found to
      provide a unique vehicle of biological origin for the intracellular delivery of
      calcium ions for supplementation. Such encapsulation can protect calcium ions
      within protein cages against dietary factors such as tannic acid (TA), oxalic
      acid (OA), and other divalent metal ions in foodstuffs. We demonstrated that the
      calcium-containing ferritin composites can be absorbed by Caco-2 cells through a
      process where a TfR1 receptor is involved, whereas the uptake of free calcium
      ions has been known to be associated with another receptor, DMT1, indicating that
      the calcium ions encapsulated in supramolecular protein cages can be internalized
      by the Caco-2 cells through a different pathway from its free analogs for calcium
      supplementation. 

PMID- 24731926
TI  - Vitamin K-dependent carboxylation of osteocalcin affects the efficacy of
      teriparatide (PTH(1-34)) for skeletal repair.
AB  - Teriparatide (PTH1-34) promotes skeletal repair and increases bone mass. Vitamin
      K is involved in bone mineralization as a coenzyme of gamma-carboxylase for Gla
      proteins, and therefore vitamin K insufficiency caused by malnutrition or
      therapeutic intake of the vitamin K antagonist warfarin could affect the efficacy
      of PTH1-34 therapy for bone repair. In the present study, we investigated whether
      vitamin K influences the efficacy of PTH1-34 therapy for bone repair in a rat
      osteotomy model. Female 12-week-old Sprague-Dawley rats were subjected to a
      closed midshaft osteotomy of the femur and randomized into four groups (n=10 per
      group): vehicle, PTH1-34 (daily 30 MUg/kg/day subcutaneous injection)+solvent
      (orally, three times a week), PTH1-34+warfarin (0.4 mg/kg/day orally, three times
      a week), and PTH1-34+vitamin K2 (menatetrenone, 30 mg/kg/day orally, three times
      a week). Serum gamma-carboxylated and uncarboxylated osteocalcin (Gla-OC and Glu
      OC) levels and radiographic healing were monitored every 2 weeks. Skeletal repair
      was assessed by micro-computed tomography, mechanical testing, and histology at
      8weeks after surgery. PTH1-34 amplified the osteotomy-induced increase in Gla-OC
      and improved the mechanical properties as well as the volumetric bone mineral
      tissue density of the fracture callus. Concurrent use of warfarin decreased the
      response to PTH1-34 therapy in terms of mechanical recovery, probably by
      impairing mineralization due to the lack of Gla-OC. Although the effects of
      combination therapy with PTH1-34 and vitamin K2 on bone repair did not
      significantly exceed those of PTH1-34 monotherapy in rats fed sufficient dietary
      vitamin K, postoperative Gla-OC levels were correlated with the mechanical
      properties of the osteotomized femur in PTH1-34-treated rats regardless of the
      use of warfarin or vitamin K2. These findings suggest the importance of vitamin K
      dependent gamma-carboxylation of OC for realizing the full effects of PTH1-34 on
      skeletal repair.

PMID- 24731927
TI  - Performance of a clonal-based HIV-1 tropism phenotypic assay.
AB  - Adequate determination of HIV-1 tropism is important in clinical and research
      settings. Genotypic and phenotypic approaches to evaluate tropism have been
      described. Phenotypic assays are widely used to determine HIV-1 tropism because
      of their sensitivity to detect minor CXCR4-using variants (X4). However they
      cannot differentiate mixed quasi-species of R5 and X4 viruses from dual-tropic
      viruses. We describe here a clonal-based HIV-1 tropism phenotypic assay. Env
      pseudo-typed viruses were produced by co-transfection of the env expression
      plasmid pcDNA3.1/V5HisTOPO and a backbone vector pNL4-3.Luc.E-R- that expresses
      the entire HIV-1 genome except for env and vpr in 293T cell cultures. Co-receptor
      use was tested by infecting U87.CD4.CCR5+ and U87.CD4.CXCR4+ cells in the
      presence or absence of co-receptor inhibitors, using 10 clones from each sample.
      The ability of the assay to detect minor variants in a viral population was
      assessed by mixing X4 and R5 clones using different ratios. Both R5 and X4
      minority variants were detected when present at greater than 0.4% in a mixture of
      envelope populations. This assay can be useful in both clinical and research
      laboratories. 

PMID- 24731928
TI  - An international multicenter study on HIV-1 drug resistance testing by 454 ultra
      deep pyrosequencing.
AB  - The detection of mutant spectra within the viral quasispecies is critical for
      therapeutic management of HIV-1 infections. Routine clinical application of
      ultrasensitive genotyping requires reproducibility and concordance within and
      between laboratories. The goal of the study was to evaluate a new protocol on HIV
      1 drug resistance testing by 454 ultra-deep pyrosequencing (454-UDS) in an
      international multicenter study. Sixteen blinded HIV-1 subtype B samples were
      provided for 454-UDS as both RNA and cDNA with viral titers of 88,600-573,000 HIV
      1 RNA copies/ml. Eight overlapping amplicons spanning protease (PR) codons 10-99
      and reverse transcriptase (RT) codons 1-251 were generated using molecular
      barcoded primers. 454-UDS was performed using the 454 Life Sciences/Roche GS FLX
      platform. PR and RT sequences were analyzed using 454 Life Sciences Amplicon
      Variant Analyzer (AVA) software. Quantified variation data were analyzed for
      intra-laboratory reproducibility and inter-laboratory concordance. Routine
      population sequencing was performed using the ViroSeq HIV-1 genotyping system.
      Eleven laboratories and the reference laboratory 454 Life Sciences sequenced the
      HIV-1 sample set. Data presented are derived from seven laboratories and the
      reference laboratory since severe study protocol execution errors occurred in
      four laboratories leading to exclusion. The median sequencing depth across all
      sites was 1364 reads per position (IQR=809-2065). 100% of the ViroSeq-reported
      mutations were also detected by 454-UDS. Minority HIV-1 drug resistance
      mutations, defined as HIV-1 drug resistance mutations identified at frequencies
      of 1-25%, were only detected by 454-UDS. Analysis of 10 preselected majority and
      minority mutations were consistently found across sites. The analysis of drug
      resistance mutations detected between 1 and 10% demonstrated high intra- and
      inter-laboratory consistency in frequency estimates for both RNA and prepared
      cDNA samples, indicating robustness of the method. HIV-1 drug resistance testing
      using 454 ultra-deep pyrosequencing results in an accurate and highly
      reproducible, albeit complex, approach to the analysis of HIV-1 mutant spectra,
      even at frequencies well below those detected by routine population sequencing. 

PMID- 24731929
TI  - Use of filter paper blood samples for rabies antibody detection in foxes and
      raccoon dogs.
AB  - The effectiveness of oral rabies vaccination in wildlife is usually evaluated by
      the detection of rabies antibodies. However, the assessment of rabies antibodies
      has several technical difficulties in the field, such as the collection, storage,
      transport and titration of blood samples, often of poor quality. The objective of
      this study was to assess the feasibility of collecting blood on a filter paper
      (FP) coupled with enzyme-linked immunosorbent assay (ELISA) titration of rabies
      antibodies in raccoon dogs and red foxes. The FP blood sampling method was found
      highly specific and repeatable in both species. Overall, results obtained with
      the FP sampling method were highly concordant with the conventional
      (venipuncture) sampling methods. Blood eluates from FP samples from foxes and
      raccoon dogs tested using ELISA showed concordance values of 92% and 95%,
      respectively, with serum samples tested using the seroneutralisation test and
      values of 95% and 91%, respectively, when the ELISA was used on both types of
      sample. The use of FP blood sampling coupled with the titration of rabies
      antibodies by ELISA provides a reliable alternative to conventional blood
      sampling and serum testing by seroneutralisation. This simple procedure is
      particularly attractive and cost-effective for assessing the effectiveness of
      oral rabies vaccination in field conditions. 

PMID- 24731930
TI  - Deep sequencing of the mantle transcriptome of the great scallop Pecten maximus.
AB  - RNA-Seq transcriptome data were generated from mantle tissue of the great
      scallop, Pecten maximus. The consensus data were produced from a time course
      series of animals subjected to a 56-day thermal challenge at 3 different
      temperatures. A total of 26,064 contigs were assembled de novo, providing a
      useful resource for both the aquaculture community and researchers with an
      interest in mollusc shell production. 

PMID- 24731932
TI  - Lateral meniscus allograft transplantation: clinical and anatomic outcomes after
      arthroscopic implantation with tibial tunnels versus open implantation without
      tunnels.
AB  - Meniscus allograft transplantation (MAT) is used to treat patients with knee pain
      after total or subtotal meniscectomy. The graft can be inserted during open or
      arthroscopic surgery. The objectives are anatomic horn positioning and strong
      fixation to the bone and capsule of an appropriately sized graft. HYPOTHESIS:
      Arthroscopic MAT with trans-tibial bone fixation ensures better mid-term
      functional outcomes and limits allograft extrusion. PATIENTS AND METHODS: We
      conducted a retrospective single-centre study of 23 consecutive patients who
      underwent MAT between 2001 and 2010. Among them, 11 had open surgery and
      anchoring of the horns without tunnels and 12 had arthroscopically-assisted
      surgery with bony fixation of the horns through trans-tibial tunnels. The two
      groups were comparable at baseline. Mean follow-up was 66.1 months. Post
      operative outcomes were assessed using the IKDC score and KOOS, standard
      radiographs of both knees, and either magnetic resonance imaging or computed
      arthrotomography. We measured joint space narrowing, meniscal extrusion in the
      sagittal and coronal planes; and the degree of cartilage coverage by the graft
      using an index developed for this study. RESULTS: The overall failure rate was
      17.4% (4/23, two cases each of complete and partial graft removal). Joint space
      narrowing increased by 28% versus the pre-operative value (P=0.009). IKDC and
      KOOS values were not significantly different between the two groups. Absolute
      meniscus extrusion was greater in the arthroscopy group (4mm vs. 3mm, P=0.03).
      DISCUSSION: Osteoarthritis of the transplanted compartment is unavoidable. Open
      surgery is associated with less meniscal extrusion. The clinical outcomes are
      independent from the technique used. Other factors require investigation,
      including graft rehabilitation, quality peripheral suturing, and intermeniscal
      ligament reconstruction. LEVEL OF EVIDENCE: IV, retrospective study.

PMID- 24731933
TI  - ECG signs of acute myocardial ischemia in the prehospital setting of a suspected
      acute coronary syndrome and its association with outcomes.
AB  - AIMS: The aims of this study were (a) to determine the prehospital prevalence of
      electrocardiographic (ECG) signs of acute myocardial ischemia in patients with
      suspected acute coronary syndrome and (b) to describe the relationships between
      the various ECG patterns and the diagnosis of acute myocardial infarction (AMI)
      and outcomes. METHODS: Prospective cohort study using data from an interventional
      trial in acute chest pain patients transported by the emergency medical services.
      These patients were classified into 3 groups: patients with ECG showing signs of
      acute myocardial ischemia, patients with ECG showing other abnormal changes
      (bundle-branch block, pacemaker rhythm, Q-wave or T-wave inversion) and patients
      without significant pathologic findings. All P values are age-adjusted. RESULTS:
      Among 1546 patients, 312 (20%) had ECG signs of acute myocardial ischemia. Of
      them, 57% had a final diagnosis of AMI versus 26% of those with other abnormal
      ECGs and 12% of those with ECG without significant pathologic findings (P<.0001).
      In all, 53% of all AMI cases involved patients without ECG signs of acute
      myocardial ischemia. Although ECG signs of acute myocardial ischemia predicted
      heart failure and ventricular tachyarrhythmias both prior to and after hospital
      admission, there was no significant difference in 30-day mortality between the 3
      patient groups (4.3%, 3.7%, and 1.2%, respectively, P=.11). CONCLUSION: Among
      patients with a clinical suspicion of AMI in the prehospital setting, the
      prevalence of ECG signs suggesting AMI was low, as was the ability to identify
      AMI patients using ECG findings only. We therefore need better instruments in the
      prehospital triage of patients with acute chest pain.

PMID- 24731931
TI  - Life and times: synthesis, trafficking, and evolution of VSG.
AB  - Evasion of the acquired immune response in African trypanosomes is principally
      mediated by antigenic variation, the sequential expression of distinct variant
      surface glycoproteins (VSGs) at extremely high density on the cell surface.
      Sequence diversity between VSGs facilitates escape of a subpopulation of
      trypanosomes from antibody-mediated killing. Significant advances have increased
      understanding of the mechanisms underpinning synthesis and maintenance of the VSG
      coat. In this review, we discuss the biosynthesis, trafficking, and turnover of
      VSG, emphasising those unusual mechanisms that act to maintain coat integrity and
      to protect against immunological attack. We also highlight new findings that
      suggest the presence of unique or highly divergent proteins that may offer
      therapeutic opportunities, as well as considering aspects of VSG biology that
      remain to be fully explored. 

PMID- 24731934
TI  - Differences in interpretation of cranial computed tomography in ED traumatic
      brain injury patients by expert neuroradiologists.
AB  - Cranial computed tomography (CT) is generally regarded as the standard for
      evaluation of structural brain injury in patients with traumatic brain injury
      (TBI) presenting to the emergency department (ED). However, the subjective nature
      of the visual interpretations of CT scans and the qualitative nature of reporting
      may lead to poor interrater reliability. This is significant because CT positive
      scans include a continuum of structural injury with differences in treatment. The
      purpose of the present study was to evaluate the consistency of readings of head
      CT scans obtained within 24 hours after mild TBI in the ED, as assessed by an
      independent adjudication panel of 3 experienced neuroradiologists. In 80.1% of
      the cases, all 3 adjudicators agreed with the determination of the presence of
      structural injury. However, when interrater agreement was assessed with respect
      to the specific classification of the injury, agreement was poor, with a kappa of
      0.3 (0.29-0.316; confidence interval [CI] 95%). When classification was
      collapsed, considering only the presence or absence of hematomas, agreement among
      all 3 adjudicators improved to 55%, but the kappa of 0.355, (0.332-0.78; CI 95%)
      was still only fair. The data suggest the need for improved recognition and
      quantification of specific structural injuries in the TBI population for better
      identification of patients requiring clinical intervention. 

PMID- 24731935
TI  - Treating patient experience and clinical outcomes equally.

PMID- 24731936
TI  - Responses of soil microbial community to different concentration of fomesafen.
AB  - Fomesafen degrades slowly in soils and has been linked to crop damage. However,
      the effect of its residues on soil microbial communities is unknown. The goal of
      this work was to assess the effect of applying three different doses of fomesafen
      on microbial community structure and functional diversity as measured by
      phospholipid fatty acid (PLFA) levels, community-level physiological profiles
      (CLPPs) and real-time PCR. Our results indicate that applying 100 times the
      recommended dose of fomesafen (T100) adversely affects soil microbial activity
      and stresses soil microbial communities as reflected by the reduced respiratory
      quotient (qCO2, QR). The PLFA analysis showed that high levels of fomesafen
      treatment (T100) decreased the total amount of PLFAs and both bacterial (both
      Gram-positive (GP) bacteria and Gram-negative (GN) bacteria) and fungal biomass
      but increased the microbial stress level. However, the BIOLOG results are not
      consistent with our other results. The addition of fomesafen significantly
      increased the average well color development, substrate utilization, and the
      functional diversity index (H'). Additionally, the abundance of the nifH (N2
      fixing bacteria) gene was reduced in the presence of high concentrations of
      fomesafen (T100). Taken together, these results suggest that the addition of
      fomesafen can alter the microbial community structure and functional diversity of
      the soil, and these parameters do not recover even after a 90-day incubation
      period. 

PMID- 24731937
TI  - Copper removal using bio-inspired polydopamine coated natural zeolites.
AB  - Herein, for the first time, natural clinoptilolite-rich zeolite powders modified
      with a bio-inspired adhesive, polydopamine (PDA), have been systematically
      studied as an adsorbent for copper cations (Cu(II)) from aqueous solution.
      Fourier transform infrared (FTIR) spectroscopy, X-ray photoelectron spectroscopy
      (XPS) and thermogravimetric analysis (TGA) revealed successful grafting of PDA
      onto the zeolite surface. The effects of pH (2-5.5), PDA treatment time (3-24h),
      contact time (0 to 24h) and initial Cu(II) ion concentrations (1 to 500mgdm(-3))
      on the adsorption of Cu(II) ions were studied using atomic absorption
      spectroscopy (AAS) and neutron activation analysis (NAA). The adsorption behavior
      was fitted to a Langmuir isotherm and shown to follow a pseudo-second-order
      reaction model. The maximum adsorption capacities of Cu(II) were shown to be
      14.93mgg(-1) for pristine natural zeolite and 28.58mgg(-1) for PDA treated
      zeolite powders. This impressive 91.4% increase in Cu(II) ion adsorption capacity
      is attributed to the chelating ability of the PDA on the zeolite surface.
      Furthermore studies of recyclability using NAA showed that over 50% of the
      adsorbed copper could be removed in mild concentrations (0.01M or 0.1M) of either
      acid or base. 

PMID- 24731938
TI  - Pharmacodynamic profiling of commonly prescribed antimicrobial drugs against
      Escherichia coli isolates from urinary tract.
AB  - Since antimicrobial resistance among uropathogens against current first line
      agents has affected the management of severe urinary tract infection, we
      determined the likelihood that antibiotic regimens achieve bactericidal
      pharmacodynamic exposures using Monte Carlo simulation for five antimicrobials
      (ciprofloxacin, ceftriaxone, piperacillin/tazobactam, ertapenem, and meropenem)
      commonly prescribed as initial empirical treatment of inpatients with severe
      community acquired urinary tract infections. Minimum inhibitory concentration
      determination by Etest was performed for 205 Brazilian community urinary tract
      infection Escherichia coli strains from 2008 to 2012 and 74 E. coli bloodstream
      strains recovered from a surveillance study. Pharmacodynamic exposure was modeled
      via a 5000 subject Monte Carlo simulation. All isolates were susceptible to
      ertapenem and meropenem. Piperacillin/tazobactam, ceftriaxone and ciprofloxacin
      showed 100%, 97.5% and 83.3% susceptibility among outpatient isolates and 98.6%,
      75.7% and 64.3% among inpatient isolates, respectively. Against outpatient
      isolates, all drugs except ciprofloxacin (82.7% in aggressive and 77.6% in
      conservative scenarios) achieved high cumulative fraction of response:
      carbapenems and piperacillin/tazobactam cumulative fraction of responses were
      close to 100%, and ceftriaxone cumulative fraction of response was 97.5%. Similar
      results were observed against inpatients isolates for carbapenems (100%) and
      piperacillin/tazobactam (98.4%), whereas ceftriaxone achieved only 76.9%
      bactericidal cumulative fraction of response and ciprofloxacin 61.9% (aggressive
      scenario) and 56.7% (conservative scenario) respectively. Based on this model,
      standard doses of beta-lactams were predicted to deliver sufficient
      pharmacodynamic exposure for outpatients. However, ceftriaxone should be avoided
      for inpatients and ciprofloxacin empirical prescription should be avoided in both
      inpatients and outpatients with complicated urinary tract infection. 

PMID- 24731939
TI  - Reprint of: construction of Specific Parallel Amplification of RNA Ends (SPARE)
      libraries for the systematic identification of plant microRNA processing
      intermediates.
AB  - MicroRNAs (miRNAs) are small RNAs that derive from endogenous precursors
      harboring foldback structures. Plant miRNA precursors are quite variable in their
      size and shape. Still, the miRNA processing machinery, consisting of DICER-LIKE1
      (DCL1) and accessory proteins recognize structural features on the precursors to
      cleave them at specific places releasing the mature miRNAs. The identification of
      miRNA processing intermediates in plants has mostly relied on a modified 5' RACE
      method, designed to detect the 5' end of uncapped RNAs. However, this method is
      time consuming and is, therefore, only practical for the analysis of a handful
      miRNAs. Here, we present a modification of this approach in order to perform
      genome-wide analysis of miRNA processing intermediates. Briefly, a reverse
      transcription is performed with a mixture of specific primers designed against
      all known miRNA precursors. miRNA processing intermediates are then specifically
      amplified to generate a library and subjected to deep sequencing. This method,
      called SPARE (Specific Parallel Amplification of 5' RNA Ends) allows the
      identification of processing intermediates for most of the Arabidopsis miRNAs.
      The results enable the determination of the DCL1 processing direction and the
      cleavage sites introduced by miRNA processing machinery in the precursors. The
      SPARE method can be easily adapted to detect miRNA-processing intermediates in
      other systems. 

PMID- 24731940
TI  - Regulation of microRNAs and their role in liver development, regeneration and
      disease.
AB  - Since their discovery more than a decade ago microRNAs have been demonstrated to
      have profound effects on almost every aspect of biology. Numerous studies in
      recent years have shown that microRNAs have important roles in development and in
      the etiology and progression of disease. This review is focused on microRNAs and
      the roles they play in liver development, regeneration and liver disease;
      particularly chronic liver diseases such as alcoholic liver disease, non
      alcoholic fatty liver disease, non-alcoholic steatohepatitis, viral hepatitis and
      primary liver cancer. The key microRNAs identified in liver development and
      chronic liver disease will be discussed together with, where possible, the target
      messenger RNAs that these microRNAs regulate to profoundly alter these processes.
      This article is part of a Directed Issue entitled: The Non-coding RNA Revolution.

PMID- 24731941
TI  - Piriformis syndrome diagnosis: on two professional cyclists.

PMID- 24731942
TI  - Interventional heart wall motion analysis with cardiac C-arm CT systems.
AB  - Today, quantitative analysis of three-dimensional (3D) dynamics of the left
      ventricle (LV) cannot be performed directly in the catheter lab using a current
      angiographic C-arm system, which is the workhorse imaging modality for cardiac
      interventions. Therefore, myocardial wall analysis is completely based on the 2D
      angiographic images or pre-interventional 3D/4D imaging. In this paper, we
      present a complete framework to study the ventricular wall motion in 4D (3D+t)
      directly in the catheter lab. From the acquired 2D projection images, a dynamic
      3D surface model of the LV is generated, which is then used to detect ventricular
      dyssynchrony. Different quantitative features to evaluate LV dynamics known from
      other modalities (ultrasound, magnetic resonance imaging) are transferred to the
      C-arm CT data. We use the ejection fraction, the systolic dyssynchrony index a 3D
      fractional shortening and the phase to maximal contraction (phii, max) to
      determine an indicator of LV dyssynchrony and to discriminate regionally
      pathological from normal myocardium. The proposed analysis tool was evaluated on
      simulated phantom LV data with and without pathological wall dysfunctions. The LV
      data used is publicly available online at https://conrad.stanford.edu/data/heart.
      In addition, the presented framework was tested on eight clinical patient data
      sets. The first clinical results demonstrate promising performance of the
      proposed analysis tool and encourage the application of the presented framework
      to a larger study in clinical practice. 

PMID- 24731944
TI  - Tumor microenvironment revisited.

PMID- 24731945
TI  - Laquinimod, an up-and-coming immunomodulatory agent for treatment of multiple
      sclerosis.
AB  - Laquinimod is a novel oral drug that is currently being evaluated for the
      treatment of relapsing-remitting multiple sclerosis (RRMS). Although the mode of
      action of laquinimod remains to be fully elucidated, current knowledge indicates
      that laquinimod exerts beneficial activities both on the peripheral immune system
      and within the central nervous system (CNS). The immunomodulatory properties have
      been deciphered primarily from studies of laquinimod in the animal model of
      multiple sclerosis, experimental autoimmune encephalomyelitis (EAE). Data
      indicate that laquinimod has a primary effect on innate immunity. Laquinimod
      modulates the function of various myeloid antigen presenting cell populations,
      which then downregulate proinflammatory T cell responses. Further, data also
      indicate that laquinimod acts directly on resident cells within the CNS to reduce
      demyelination and axonal damage. Results from clinical trials that tested
      laquinimod in RRMS demonstrated that it reduced relapse rate and the mean
      cumulative number of active lesions, and had a more marked reduction in
      disability progression than relapse rate. Laquinimod treatment was associated
      with an excellent safety and tolerability profile. These data indicate that
      laquinimod will offer a valuable new treatment option for RRMS patients. 

PMID- 24731943
TI  - Elements and machinery of non-coding RNAs: toward their taxonomy.
AB  - Although recent transcriptome analyses have uncovered numerous non-coding RNAs
      (ncRNAs), their functions remain largely unknown. ncRNAs assemble with proteins
      and operate as ribonucleoprotein (RNP) machineries, formation of which is thought
      to be determined by specific fundamental elements embedded in the primary RNA
      transcripts. Knowledge about the relationships between RNA elements, RNP
      machinery, and molecular and physiological functions is critical for
      understanding the diverse roles of ncRNAs and may eventually allow their
      systematic classification or "taxonomy." In this review, we catalog and discuss
      representative small and long non-coding RNA classes, focusing on their currently
      known (and unknown) RNA elements and RNP machineries. 

PMID- 24731946
TI  - Glial cell line-derived neurotrophic factor promotes increased phenotypic marker
      expression in femoral sensory and motor-derived Schwann cell cultures.
AB  - Schwann cells (SCs) secrete growth factors and extracellular matrix molecules
      that promote neuronal survival and help guide axons during regeneration.
      Transplantation of SCs is a promising strategy for enhancing peripheral nerve
      regeneration. However, we and others have shown that after long-term in vitro
      expansion, SCs revert to a de-differentiated state similar to the phenotype
      observed after injury. In vivo, glial cell-line derived neurotrophic factor
      (GDNF) may guide the differentiation of SCs to remyelinate regenerating axons.
      Therefore, we hypothesized that exogenous GDNF may guide the differentiation of
      SCs into their native phenotypes in vitro through stimulation of GDNF family
      receptor (GFR)alpha-1. When activated in SCs, GFRalpha-1 promotes phosphorylation
      of Fyn, a Src family tyrosine kinase responsible for mediating downstream
      signaling for differentiation and proliferation. In this study, SCs harvested
      from the sensory and motor branches of rat femoral nerve were expanded in vitro
      and then cultured with 50 or 100ng/mL of GDNF. The exogenous GDNF promoted
      differentiation of sensory and motor-derived SCs back to their native phenotypes,
      as demonstrated by decreased proliferation after 7days and increased expression
      of S100Betabeta and phenotype-specific markers. Furthermore, inhibiting Fyn with
      Src family kinase inhibitors, PP2 and SU6656, and siRNA-mediated knockdown of Fyn
      reduced GDNF-stimulated differentiation of sensory and motor-derived SCs. These
      results demonstrate that activating Fyn is necessary for GDNF-stimulated
      differentiation of femoral nerve-derived SCs into their native phenotypes in
      vitro. Therefore GDNF could be incorporated into SC-based therapies to promote
      differentiation of SCs into their native phenotype to improve functional nerve
      regeneration. 

PMID- 24731948
TI  - Neuroprotective dimethyl fumarate synergizes with immunomodulatory interferon
      beta to provide enhanced axon protection in autoimmune neuroinflammation.
AB  - INTRODUCTION: Despite recent advances in development of treatments for multiple
      sclerosis, there is still an unmet need for more effective and also safe
      therapies. Based on the modes of action of interferon-beta (IFN-beta) and
      dimethyl fumarate (DMF), we hypothesized that anti-inflammatory and
      neuroprotective effects may synergize in experimental autoimmune
      encephalomyelitis (EAE). METHODS: EAE was induced in C57BL/6 mice by immunization
      with MOG35-55-peptide. Murine IFN-beta was injected s.c. every other day at
      10.000IU, and DMF was provided at 15mg/kg by oral gavage twice daily. Control
      mice received PBS injections and were treated by oral gavage with the vehicle
      methylcellulose. Mice were scored daily by blinded observers and histological,
      FACS and cytokine studies were performed to further elucidate the underlying
      mechanism of action. RESULTS: Combination therapy significantly ameliorated EAE
      disease course in comparison to controls and monotherapy with IFN-beta.
      Histological analyses showed a significant effect on axon preservation with
      almost twice as much axons present in inflamed lesions as compared to control.
      Remarkably, the effect on axonal preservation was more pronounced under
      combination therapy than with both monotherapies. Neither monotherapy nor
      combination therapy demonstrated modulation of cytokines and frequency of antigen
      presenting cells. DISCUSSION: Combination of IFN-beta and DMF resulted in greater
      beneficial effects with improved tissue protection as compared to the respective
      monotherapies. Further combination studies of these safe therapies in human
      disease are warranted.

PMID- 24731947
TI  - The neuroanatomy of sexual dimorphism in opioid analgesia.
AB  - The influence of sex has been neglected in clinical studies on pain and
      analgesia, with the vast majority of research conducted exclusively in males.
      However, both preclinical and clinical studies indicate that males and females
      differ in both the anatomical and physiological composition of central nervous
      system circuits that are involved in pain processing and analgesia. These
      differences influence not only the response to noxious stimuli, but also the
      ability of pharmacological agents to modify this response. Morphine is the most
      widely prescribed opiate for the alleviation of persistent pain in the clinic;
      however, it is becoming increasingly clear that morphine is less potent in women
      compared to men. This review highlights recent research identifying
      neuroanatomical and physiological dimorphisms underlying sex differences in pain
      and opioid analgesia, focusing on the endogenous descending pain modulatory
      circuit. 

PMID- 24731949
TI  - Isolation and molecular characterization of the shikimate dehydrogenase domain
      from the Toxoplasma gondii AROM complex.
AB  - The apicomplexan parasite Toxoplasma gondii, the etiologic agent of
      toxoplasmosis, is estimated to infect 10-80% of different human populations. T.
      gondii encodes a large pentafunctional polypeptide known as the AROM complex
      which catalyzes five reactions in the shikimate pathway, a metabolic pathway
      required for the biosynthesis of the aromatic amino acids and a promising target
      for anti-parasitic agents. Here, we present the isolation, cloning and kinetic
      characterization of the shikimate dehydrogenase domain (TgSDH) from the T. gondii
      AROM complex. Recombinant TgSDH catalyzed the NADP(+)-dependent oxidation of
      shikimate in the absence of the remaining AROM domains and was sensitive to
      inhibition by a previously identified SDH inhibitor. Analysis of the TgSDH amino
      acid sequence revealed a number of novel insertions not found in SDH homologs
      from other organisms. Nevertheless, a three-dimensional structural model of TgSDH
      predicts a high level of conservation in the 'core' structure of the enzyme. 

PMID- 24731950
TI  - Polyploidy and hybridization as main factors of speciation: complex reticulate
      evolution within the grass genus Helictochloa.
AB  - To study the origin and evolution of naturally occurring polyploids, we performed
      phylogenetic analyses of nuclear ribosomal DNA spacers combined with molecular
      cytogenetics in 55 accessions of 27 taxa of the oat genus Helictochloa. A complex
      pattern of reticulate evolution was revealed with many diploid species and
      extensive polyploidy up to 20x. Altogether 11 groups of internal transcribed
      spacer (ITS) sequences can be distinguished. Sequences from 1-3 different ITS
      lineages were detected in polyploids. Cytogenetic data allow reconstruction of 8
      basic monoploid chromosome sets. Six of these genomes occur in different
      combinations in the polyploid species. Two genomes are only found in diploids.
      Our sequence and karyological data highlight the occurrence of autopolyploidy and
      allopolyploidy, provide new information about the evolutionary history of taxa,
      and allow a more accurate systematic treatment of the concerned species. The
      geographical distribution of the 11 ITS lineages distinguished is highly
      structured and points to an origin of the genus in western Asia, presumably in
      grasslands like steppes or mountain steppes and meadows. The evolutionary basal
      lineages are of Asian, Minor Asian and east Mediterranean distribution and are
      present also in North America. The western and central parts of the Mediterranean
      and northern Europe harbor the modern lineages.

PMID- 24731951
TI  - The diversity of Iranian nursing students' clinical learning styles: a
      qualitative study.
AB  - BACKGROUND: Numerous factors, including learning styles, affect the learning
      process of nursing students. Having insights about students' learning styles
      helps promoting the quality of education. The aim of this study was to explore
      the Iranian baccalaureate nursing students' learning styles in clinical settings.
      METHODS: A qualitative design using a content analysis approach was used to
      collect and analyze data. Semi-structured interviews were conducted with fifteen
      Iranian baccalaureate nursing students selected using a purposive sample method.
      FINDINGS: During data analysis, it was found that nursing students employed
      different clinical learning styles such as 'thoughtful observation,' 'learning by
      thinking,' and 'learning by doing'. CONCLUSION: Students adopt different learning
      strategies in clinical practice. Designing teaching strategies based on students'
      learning styles can promote students' learning and maximize their academic and
      clinical practice success. Nursing educators, curriculum designers, and students
      can use the findings of this study to improve the quality of nursing education in
      both the classroom and clinical settings.

PMID- 24731952
TI  - Clinical factors associated with failed trials of labor in late preterm and term
      twin pregnancies.
AB  - OBJECTIVE: To evaluate the perinatal outcomes and clinical factors of
      unsuccessful trials of labor (TOLs) in late preterm and term twin pregnancies.
      METHODS: We enrolled 896 consecutive twin pregnancies delivered between 1999 and
      2012 in a single center, which met the following inclusion criteria: a vertex
      first twin, live twins, and attempted TOLs after 34 weeks. Obstetric
      characteristics and perinatal outcomes were compared between vaginal delivery and
      cesarean delivery groups. RESULTS: Successful TOLs were carried out in 81%
      (726/896). Failed TOLs occurred in 15% (37/247) of late preterm twins and 20%
      (133/649) of term twins. Comparisons of neonatal outcomes between the groups
      showed no significant differences in NICU admission, ventilator use, and
      composite morbidity. On univariable analysis, nulliparity, preeclampsia, induced
      labor, excessive weight gain, and intertwin weight discordance of >30% showed
      significant associations with failed TOLs. Multivariable analyses revealed
      nulliparity (adjusted odds ratio 9.89, 95% confidence interval 4.64-21.1) and
      preeclampsia (adjusted odds ratio 2.17, 95% confidence interval 1.30-3.63) as
      significantly associated with failed TOLs. CONCLUSION: In late preterm and term
      twins, trials of labor can be performed successfully without a significant
      increase in adverse neonatal outcomes. Nulliparity and preeclampsia are clinical
      factors associated with failed TOLs in twin pregnancies.

PMID- 24731953
TI  - Targeting complement system to treat myasthenia gravis.
AB  - While the complement system is desired for protective immunity, antibody- and
      complement-mediated neuromuscular junction (NMJ) destruction, a hallmark of
      myasthenia gravis (MG) or experimental autoimmune MG (EAMG), is a significant
      concern. Evidence suggests that the binding of complement factors to the
      pathogenic anti-acetylcholine receptor (AChR) autoantibody induces the formation
      of membrane attack complexes (MAC), which ultimately lead to NMJ destruction and
      muscle weakness. Studies corroborating the evidence show that the complement (C3
      C6)-deficient or complement inhibitor (anti-C1q, soluble CR1, anti-C6, and C5
      inhibiting peptide)-treated animals are highly resistant to EAMG induction,
      whereas the deficiency of the naturally occurring complement inhibitors, such as
      the decay-accelerating factor (DAF), increases EAMG susceptibility. Notably, the
      complement-inhibited animals do not exhibit significant immunosuppression but
      only a marginal reduction in the production of certain cytokines and
      immunoglobulin isotypes. A preliminary clinical trial using antibody-based C5
      inhibitor eculizumab has been shown to be of potential use for MG treatment. The
      inhibition of the classic complement pathway (CCP) alone appears to be enough to
      suppress EAMG, suggesting that the complement inhibitors targeting specifically
      the classic pathway could effectively treat MG without causing immunosuppressive
      and other side effects. For instance, a recent non-antibody-based therapeutic
      approach selectively targeting the CCP component C2 by small interfering RNA
      (siRNA) has proven useful in EAMG treatment. The treatment strategies developed
      for MG might also be beneficial for other complement-mediated autoimmune
      diseases.

PMID- 24731954
TI  - Serum glucose adjusted cut-off values for normal cerebrospinal fluid/serum
      glucose ratio: implications for clinical practice.
AB  - BACKGROUND: Calculation of the cerebrospinal fluid/serum glucose (CSF/SGlu) ratio
      is part of the routine CSF work-up, however, different cut-off values ranging
      from 0.3 to 0.5 have been suggested so far to distinguish physiological from
      pathological conditions. The objective of this study was to determine cut-off
      values for normal CSF/SGlu ratio dependent on serum glucose concentrations.
      METHODS: We screened our database for paired CSF and serum samples, which have
      been collected by lumbar puncture, were processed within 1 h after withdrawal,
      showed cell count <15/3, erythrocyte count <1500/3 and normal CSF total protein
      resulting in 1036 sample pairs. Glucose concentrations in CSF and serum were
      measured by enzymatic spectrophotometry. RESULTS: Median glucose concentration in
      CSF was approximately 60% of that in serum. CSF/SGlu ratios negatively correlated
      with serum glucose levels (R=-0.586, p<0.001) and cut-off values for normal
      CSF/SGlu ratio defined as the 5th percentile were 0.5 for patients with serum
      glucose concentrations <100 mg/dL, 0.4 for those with a glucose level of 100-149
      mg/dL and 0.3 for serum glucose concentrations >=150 mg/dL. CONCLUSIONS: CSF/SGlu
      ratio inversely correlates with serum glucose concentrations in a non-linear
      manner. These findings suggest that cut-off values for normal CSF/SGlu ratio must
      be adjusted to serum glucose levels, probably explaining the considerably varying
      cut-offs that have been reported so far.

PMID- 24731955
TI  - Improvement and evaluation of a 1,2-dioleoylglycerol method for measuring
      pancreatic lipase catalytic activity in serum.

PMID- 24731956
TI  - In vitro protective effects of Scutellaria litwinowii root extract against H2O2
      induced DNA damage and cytotoxicity.
AB  - BACKGROUND: Despite the wide range of investigations on the therapeutic
      potentials of herbal extracts in cancer cell lines, there is not usually enough
      data on their probable effects on normal cells. Recently, both anti-tumoral and
      anti-oxidant properties of Scutellaria litwinowii extracts have been reported on
      different cancer cell lines. In the present study, the possible protective
      effects of S. litwinowii root extracts against cytotoxicity and DNA damage
      induced by hydrogen peroxide (H2O2) on normal cells were investigated using MTT
      and Comet assays, respectively. METHODS: A method of sequential extraction with
      solvents of different polarities was used to generate methanolic, de-fatted, and
      dichloromethane fractions. Both MTT and Comet assays were performed here to
      assess, respectively, changes in cell viability and levels of DNA damage from
      H2O2. In a pre-treatment regimen, test materials were applied to the cells prior
      to H2O2 treatment, while in a co-treatment protocol, cells were treated
      simultaneously with H2O2 and extracts. RESULTS: In the co-treatment studies, only
      methanolic extract at 1,000 MUg/mL (p<0.001) imparted a significant protective
      effect as shown in the MTT assay. Pre-treatment of cells for 24 h with different
      concentrations of the test materials did not lead to any significant protection.
      Results from the Comet assays in the co-treatment studies suggested a significant
      (p<0.01) protective effect of the test materials against DNA damage caused by
      H2O2. However, in the pre-treatment studies, only methanolic extract at >=500
      MUg/mL showed a protective effect (p<0.01). CONCLUSIONS: Considering the probable
      high levels of phenolic and flavonoid compounds in the methanolic extract, these
      compounds may impart the noted protective effects of the S. litwinowii root
      through the scavenging of free radicals.

PMID- 24731957
TI  - Physician gender, physician patient-centered behavior, and patient satisfaction:
      a study in three practice settings within a hospital.
AB  - OBJECTIVE: To compare male and female physicians on patient-centeredness and
      patients' satisfaction in three practice settings within a hospital; to test
      whether satisfaction is more strongly predicted by patient-centeredness in male
      than female physicians. METHODS: Encounters between physicians (N=71) and
      patients (N=497) in a hospital were videotaped and patients' satisfaction was
      measured. Patient-centeredness was measured by trained coders. RESULTS: In the
      outpatient setting, female physicians were somewhat more patient-centered than
      male physicians; patient satisfaction did not differ. In the inpatient and
      emergency room settings, female physicians were notably more patient-centered
      than male physicians; satisfaction paralleled these differences. Nevertheless,
      there was some, though mixed, evidence that patient-centeredness predicted
      satisfaction more strongly in male than female physicians, suggesting that
      patients valued patient-centered behavior more in male than female physicians.
      CONCLUSION: Even though satisfaction mirrored the different behavior styles of
      male and female physicians in the inpatient and emergency room settings, in all
      settings male physicians got somewhat more credit for being patient-centered than
      female physicians did. PRACTICE IMPLICATIONS: If female physicians do not
      consistently receive credit for high patient-centeredness in the eyes of
      patients, this could lead female physicians to reduce their patient-centered
      behavior.

PMID- 24731958
TI  - Treatment with neuraminidase inhibitors for high-risk patients with influenza:
      why is adherence to antiviral treatment recommendations so low?

PMID- 24731959
TI  - Influenza-like illness, the time to seek healthcare, and influenza antiviral
      receipt during the 2010-2011 influenza season-United States.
AB  - BACKGROUND: Few data exist describing healthcare-seeking behaviors among persons
      with influenza-like illness (ILI) or adherence to influenza antiviral treatment
      recommendations. METHODS: We analyzed adult responses to the Behavioral Risk
      Factor Surveillance System in 31 states and the District of Columbia (DC) and
      pediatric responses in 25 states and DC for January-April 2011 by demographics
      and underlying health conditions. RESULTS: Among 75 088 adult and 15 649 child
      respondents, 8.9% and 33.9%, respectively, reported ILI. ILI was more frequent
      among adults with asthma (16%), chronic obstruction pulmonary disease (COPD;
      26%), diabetes (12%), heart disease (19%), kidney disease (16%), or obesity
      (11%). Forty-five percent of adults and 57% of children sought healthcare for
      ILI. Thirty-five percent of adults sought care <= 2 days after ILI onset. Seeking
      care <= 2 days was more frequent among adults with COPD (48%) or heart disease
      (55%). Among adults with a self-reported physician diagnosis of influenza, 34%
      received treatment with antiviral medications. The only underlying health
      condition with a higher rate of treatment was diabetes (46%). CONCLUSIONS: Adults
      with underlying health conditions were more likely to report ILI, but the
      majority did not seek care promptly, missing opportunities for early influenza
      antiviral treatment.

PMID- 24731960
TI  - Modified S-ileal neobladder for continent urinary diversion: functional and
      urodynamic results after 20 years of follow-up.
AB  - OBJECTIVE: To report continence and urodynamic findings after radical cystectomy
      and urinary diversion with modified S-ileal neobladder between January 1993 and
      January 2013. PATIENTS AND METHODS: 181 patients were enrolled. Continence
      status, reservoir sensation, compliance, capacity and activity were assessed.
      RESULTS: Daytime continence was reported by 88.0, 98.4 and 99.2%, while nighttime
      continence was reported by 70.2, 94.0 and 95.8% of our patients at 6 months, 5
      years and 20 years, respectively. Enterocystometric capacity and maximum
      reservoir pressure were 366 vs. 405 ml and 502 ml, and 29 vs. 18 and 11 cm H2O,
      at 6 months, 5 years and 20 years, respectively. Median post-void residual urine
      volume was 32 ml at 6 months, 50 ml at 5 years and 120 ml at 20 years.
      CONCLUSIONS: The modified S-ileal neobladder technique has a very good long
      lasting functional outcome, with high day- and nighttime continence levels as
      well as high acceptability rates from our patients.

PMID- 24731961
TI  - Vitamin D levels in children, adolescents, and young adults with juvenile-onset
      systemic lupus erythematosus: a cross-sectional study.
AB  - BACKGROUND: SS and LC contributed equally to this manuscript. Hypovitaminosis D
      is common in the general population. Although many studies on 25-hydroxyvitamin D
      (25(OH)D) are available on systemic lupus erythematosus (SLE), few data are
      reported in juvenile-onset SLE (JSLE) patients. DESIGN: This study aimed to
      assess serum 25(OH)D levels in JSLE patients and to identify risk factors for
      vitamin D deficiency in this population. METHODS: Forty-five Caucasian JSLE
      patients (36 females, nine males; mean age 18.9+/-6.3 years) and 109 age- and sex
      matched healthy controls entered the study. Dual-energy X-ray absorptiometry
      (DXA) scans of the lumbar spine, serum calcium and phosphate, bone-specific
      alkaline phosphatase (BSAP), parathyroid hormone (PTH), and 25(OH)D were
      assessed. The data were compared with an age- and sex-matched control group
      including 109 Caucasian healthy subjects. RESULTS: JSLE patients exhibited lower
      25(OH)D levels than controls (p<0.005), with the lower values observed in
      patients with active vs. inactive disease (p<0.05). JSLE patients exhibited
      reduced total calcium levels (p<0.001) and higher phosphate levels (p<0.001),
      BSAP (p<0.001) and PTH (p<0.001) than controls. In addition, JSLE patients
      exhibited lower spine bone mineral apparent density (BMAD) SDS values than
      controls (p<0.001), with higher values in patients with 25(OH)D sufficiency and
      insufficiency than in those with 25(OH)D deficiency (p<0.001). CONCLUSIONS:
      Patients with JSLE have significantly lower 25(OH)D levels than controls.
      Therefore, vitamin D supplementation may be useful to normalize bone mass and
      quality in subjects with JSLE.

PMID- 24731962
TI  - Sleep disorders in systemic lupus erythematosus. Does vitamin D play a role?
AB  - OBJECTIVES: Sleep disorders are common among patients with systemic lupus
      erythematosus (SLE) with unclear underlying mechanisms. We assessed the role of
      vitamin D in sleep quality of patients with SLE. METHODS: A retrospective study
      was conducted on women with SLE for whom the following data were available at the
      same time; sleep quality (Pittsburgh Sleep Quality Index (PSQI)), disease
      activity, cumulative disease damage, psychological state (Hospital Anxiety and
      Depression Scale (HADS)), and serum vitamin D level. Bivariate and regression
      analyses were computed to find contributors of sleep quality. RESULTS: In total,
      63 women were studied. Serum vitamin D level was correlated with physical
      activity (r=0.310, p=0.015), season of assessment (r=-0.302, p=0.016), the PSQI
      global score (r=-0.262, p=0.043), anxiety score (r=-0.298, p=0.021), and non
      significantly with depression score (r=-0.218, p=0.094). Including all variables
      into a linear regression model, vitamin D level was independently associated with
      the global PSQI score (beta=-0.364, p=0.042). Association of vitamin D level with
      psychological state disappeared after controlling for season of assessment (beta=
      0.248, p=0.154). CONCLUSIONS: We found a role for vitamin D in sleep quality of
      SLE patients. Further studies are warranted to confirm these results and to find
      possible mechanisms of action.

PMID- 24731963
TI  - Acetaminophen attenuates obesity-related renal injury through ER-mediated stress
      mechanisms.
AB  - BACKGROUND/AIMS: Obesity is an independent risk factor for the development of
      kidney disease. The purpose of this study was to determine how obesity may
      contribute to renal damage and whether acetaminophen ingestion can diminish
      obesity-associated renal cell injury in the obese Zucker rat model. METHODS: Male
      obese Zucker rats (4 weeks old, n=6) were treated with acetaminophen (30 mg / kg
      body weight / day) for 26 weeks. Age matched obese control (OC), obese vehicle
      (OV, 0.073 mL DMSO/kg/d), and lean Zucker rats (LC) were used to determine the
      effects of treatment and obesity. RESULTS: Compared to lean control rats, renal
      lipid deposition, expression of the endoplasmic reticulum (ER) stress protein
      GRP78 and activation of the ER stress-related eIF2alpha-ATF4-CHOP, caspase 12,
      and JNK-MAPK signaling pathways were increased in the obese control and obese
      vehicle rats. These alterations were associated with the elevated renal cell
      apoptosis and urinary albumin excretion. Acetaminophen treatment decreased renal
      lipid deposition, ER-stress related signaling, apoptosis and albuminuria.
      CONCLUSION: These data suggest that the protective effects of low dose
      acetaminophen on renal injury are mediated, at least in part, through attenuation
      of ER stress.

PMID- 24731964
TI  - Genetic diversity and population structure of the New World screwworm fly from
      the Amazon region of Brazil.
AB  - Cochliomyia hominivorax (Coquerel) is a myiasis fly that causes economic losses
      to livestock farmers in warmer American regions. Previous studies of this pest
      had found population structure at north and south of the Amazon Basin, which was
      considered to be a barrier to dispersal. The present study analyzed three
      mitochondrial DNA (mtDNA) markers and eight nuclear microsatellite loci to
      investigate for the first time the genetic diversity and population structure
      across the Brazilian Amazon region (Amazonia). Both mtDNA and microsatellite data
      supported the existence of much diversity and significant population structure
      among nine regional populations of C. hominivorax, which was found to be
      surprisingly common in Amazonia. Forty-six mtDNA haplotypes were identified, of
      which 39 were novel and seven had previously been found only at south of
      Amazonia. Seventy microsatellite alleles were identified by size, moderate to
      high values of heterozygosity were discovered in all regions, and a Bayesian
      clustering analysis identified four genetic groups that were not geographically
      distributed. Reproductive compatibility was also investigated by laboratory
      crossing, but no evidence of hybrid dysgenesis was found between an Amazonian
      colony and one each of from Northeast and Southeast Brazil. The results have
      important implications for area-wide control by the Sterile Insect Technique. 

PMID- 24731965
TI  - Detection of micronuclei in hepatocytes isolated from young adult rats repeatedly
      treated with N-nitrosodi-n-propylamine.
AB  - To assess the effectiveness of the multiple dose liver micronucleus (MN) assay,
      the induction of micronuclei by N-nitrosodi-n-propylamine (NDPA), a genotoxic
      rodent carcinogen, was compared in hepatocytes (HEPs) and bone marrow (BM) cells.
      Young adult male rats were treated orally with NDPA at 6 weeks of age for 14 days
      using daily doses of 10, 20 and 40mg/kg. Samples of the liver and BM tissues were
      harvested from each animal one day following the last treatment with NDPA and
      were evaluated for the frequencies of micronucleated cells. Repeated doses with
      40mg/kg/day of NDPA caused systemic and hepatic toxicity, including suppressed
      body weight gains and histopathological hepatic lesions. The frequencies of
      micronucleated HEPs were significantly increased in all the NDPA-treated groups
      in a dose-dependent manner. In contrast, the induction of micronuclei in the BM
      was undetectable, even at the high dose level of 40mg/kg, for which the
      inhibition of hematopoiesis was observed. For the detection of micronucleated
      HEPs induced by NDPA treatment, a 14-day administration period is adequate. The
      liver MN assay using naive young adult rats may be integrated into general
      repeated-dose toxicity studies including histopathological examinations. Our
      results suggest that the liver MN assay using multiple doses is more efficient
      and sensitive than the BM MN assay in detecting the in vivo genotoxic potential
      of NDPA. 

PMID- 24731966
TI  - Barrier properties of cultured retinal pigment epithelium.
AB  - The principal function of an epithelium is to form a dynamic barrier that
      regulates movement between body compartments. Each epithelium is specialized with
      barrier functions that are specific for the tissues it serves. The apical surface
      commonly faces a lumen, but the retinal pigment epithelium (RPE) appears to be
      unique by a facing solid tissue, the sensory retina. Nonetheless, there exists a
      thin (subretinal) space that can become fluid filled during pathology. RPE
      separates the subretinal space from the blood supply of the outer retina, thereby
      forming the outer blood-retinal barrier. The intricate interaction between the
      RPE and sensory retina presents challenges for learning how accurately culture
      models reflect native behavior. The challenge is heightened by findings that
      detail the variation of RPE barrier proteins both among species and at different
      stages of the life cycle. Among the striking differences is the expression of
      claudin family members. Claudins are the tight junction proteins that regulate
      ion diffusion across the spaces that lie between the cells of a monolayer.
      Claudin expression by RPE varies with species and life-stage, which implies
      functional differences among commonly used animal models. Investigators have
      turned to transcriptomics to supplement functional studies when comparing native
      and cultured tissue. The most detailed studies of the outer blood-retinal barrier
      have focused on human RPE with transcriptome and functional studies reported for
      human fetal, adult, and stem-cell derived RPE. 

PMID- 24731967
TI  - Intranasal coadministration of Cholera toxin with amoeba lysates modulates the
      secretion of IgA and IgG antibodies, production of cytokines and expression of
      pIgR in the nasal cavity of mice in the model of Naegleria fowleri
      meningoencephalitis.
AB  - The nasal mucosa is the first contact with antigens to induce IgA response. The
      role of this site has rarely been studied. We have shown than intranasal
      administration with Naegleria fowleri lysates plus Cholera toxin (CT) increased
      the protection (survival up to 100%) against N. fowleri infection in mice and
      apparently antibodies IgA and IgG together with polymorphonuclear (PMN) cells
      avoid the attachment of N. fowleri to apical side of the nasal epithelium. We
      also observed that nasal immunization resulted in the induction of antigen
      specific IgG subclasses (IgG1 and IgG2a) in nasal washes at days 3 and 9 after
      the challenge and IgA and IgG in the nasal cavity, compared to healthy and
      infected mice. We found that immunization with both treatments, N. fowleri
      lysates plus CT or CT alone, increased the expression of the genes for alpha
      chain, its receptor (pIgR), and it also increased the expression of the
      corresponding proteins evidenced by the ~65 and ~74kDa bands, respectively. Since
      the production of pIgR, IgA and IgG antibodies, is up-regulated by some factors,
      we analyzed the expression of genes for IL-10, IL-6, IFN-gamma, TNF-alpha and IL
      1beta by using RT-PCR of nasal passages. Immunization resulted in an increased
      expression of IL-10, IL-6, and IFN-gamma cytokines. We also aimed to examine the
      possible influences of immunization and challenge on the production of
      inflammatory cytokines (TNF-alpha and IL-1beta). We observed that the stimulus of
      immunization inhibits the production of TNF-alpha compared to the infected group
      where the infection without immunization causes an increase in it. Thus, it is
      possible that the coexistence of selected cytokines produced by our immunization
      model may provide a highly effective immunological environment for the production
      of IgA, IgG and pIgR as well as a strong activation of the PMN in mucosal
      effector tissue such as nasal passages. 

PMID- 24731968
TI  - Serum adropin levels are decreased in patients with acute myocardial infarction.
AB  - OBJECTIVE: Adropin is a recently identified bioactive protein that is important
      for energy homeostasis and maintaining insulin sensitivity. We sought to detect
      serum adropin levels in acute myocardial infarction (AMI) patients. METHODS: We
      enrolled 138 AMI patients, 114 stable angina pectoris (SAP) patients and 75
      controls. Adropin levels were measured by enzyme-linked immunosorbent assay
      (ELISA). RESULTS: Serum adropin levels were significantly lower in patients with
      AMI compared with SAP patients or controls (P<0.01). Multivariate logistic
      regression demonstrated that lower adropin was the independent predictor for the
      presence of AMI in coronary artery disease (CAD) patients (P<0.01). Serum adropin
      levels were negatively associated with body mass index (BMI) (P<0.01) and
      triglyceride levels (P<0.05) in AMI patients. CONCLUSION: Decreased serum adropin
      levels are associated with the presence of AMI in CAD patients. These results
      revealed that adropin might represent as a novel biomarker for predicting AMI
      onset in CAD patients.

PMID- 24731969
TI  - Metabolites profile of Xian-Ling-Gu-Bao capsule, a traditional Chinese medicine
      prescription, in rats by ultra performance liquid chromatography coupled with
      quadrupole time-of-flight tandem mass spectrometry analysis.
AB  - Xian-Ling-Gu-Bao capsule (XLGB), a well-known traditional Chinese medicine
      prescription (TCMP), is widely used for the treatment of osteoporosis. However,
      due to lack of metabolism research, the effective material of XLGB is still
      unknown. It entails a huge obstacle for the clinical-safe medication
      administration and quality control of XLGB. To explore the metabolic fate of
      multiple components of XLGB, herein, we proposed a "representative structure
      based homologous xenobiotics identification" (RSBHXI) strategy based on ultra
      performance liquid chromatography coupled with quadrupole time-of-flight tandem
      mass spectrometry (UPLC/Q-TOF-MS) and mass defect filter (MDF) technique. A total
      of 147 XLGB-related xenobiotics were identified or tentatively characterized in
      rat biofluids after oral administration of XLGB, including 134 (57 prototype
      components and 77 metabolites) in plasma, 93 (37 prototype components and 56
      metabolites) in urine and 118 (46 prototype components and 72 metabolites) in
      bile. Our results indicated that prenylated flavonol glycosides from Herba
      epimedii, prenylated flavonoids from Fructus psoraleae, saponins from Radix
      dipsaci and Rhizoma anemarrahenae, as well as tanshinones from Radix Salviae
      Miltiorrhizae were major absorbed chemical components of XLGB. Hydrolysis,
      glucuronidation and sulfation were major metabolic reactions of XLGB. As more
      xenobiotics were detected in bile than those in urine, it demonstrated that
      multiple components of XLGB underwent comprehensive hepatobiliary excretion. The
      present study expands our knowledge about the metabolism of XLGB which will be
      conducive to revealing its in vivo pharmacological material basis. In addition,
      the application of RSBHXI strategy provides a new approach for metabolite
      identification of TCMPs and other complex mixture. 

PMID- 24731970
TI  - Development and validation of a novel stability-indicating HPLC method for the
      simultaneous assay of betamethasone-17-valerate, fusidic acid, potassium sorbate,
      methylparaben and propylparaben in a topical cream preparation.
AB  - A novel stability-indicating reversed phase high performance liquid
      chromatographic (RP-HPLC) method for the simultaneous assay of betamethasone-17
      valerate, fusidic acid and potassium sorbate as well as methyl- and propylparaben
      in a topical cream preparation has been developed. A 100mm*3.0mm ID. Ascentis
      Express C18 column maintained at 30 degrees C and UV detection at 240nm were
      used. A gradient programme was employed at a flow-rate of 0.75ml/min. Mobile
      phase A comprised of an 83:17 (v/v) mixture of acetonitrile and methanol and
      mobile phase B of a 10g/l solution of 85% phosphoric acid in purified water. The
      method has been validated according to current International Conference on
      Harmonisation (ICH) guidelines and applied during formulation development and
      stability studies. The procedure has been shown to be stability-indicating for
      the topical cream. 

PMID- 24731972
TI  - Psychosocial correlates of parenting a child with autistic disorder.
AB  - BACKGROUND: The lifelong experience of raising a child with a complex
      developmental disability such as autistic disorder is considered one of the most
      significant parenting stressors, with the potential to spill over into various
      areas of the life of parents. Therefore, studying the psychological functioning
      for parents of children with developmental disabilities requires the
      consideration of multiple factors acting and interacting concurrently. PURPOSE:
      The purpose of this study was to examine the relationship between two sets of
      variables in a sample of parents of children with autistic disorder. The first
      set was composed of the parents' characteristics and the coping strategies used.
      The second set was composed of three stress subscales-parental distress (PD),
      parent-child dysfunctional interaction (PCDI), and difficult child (DC)-and the
      parental quality of life (QOL). METHODS: Canonical correlation multivariate
      analysis was used to examine the relationship between the sets of variables in
      184 Jordanian parents of children with autistic disorder. RESULTS: The analyses
      revealed that the parents who have higher incomes, use diverse problem-solving
      strategies, exhibit less escape-avoidance, and exhibit less responsibility
      acceptance behavior tended to report lower PD, PCDI, and DC scores and a higher
      QOL score. The analyses also revealed that being an older parent, having more
      time since the child's autistic diagnosis, and using more distancing coping
      strategies were associated with lower PD scores, higher PCDI and DC scores, and
      better QOL. CONCLUSIONS: This study is the first to investigate a wide range of
      parental psychosocial impacts as well as several sociodemographic factors that
      are possibly associated with raising a child with autistic disorder. The results
      indicate that health professionals working with parents of children with autistic
      disorder need to consider holistically the factors that can potentially affect
      the parents' health and well-being and provide care that focuses on the parents
      as both clients and caregivers.

PMID- 24731971
TI  - Application of physiologically-based toxicokinetic modelling in oral-to-dermal
      extrapolation of threshold doses of cosmetic ingredients.
AB  - The application of physiologically based toxicokinetic (PBTK) modelling in route
      to-route (RtR) extrapolation of three cosmetic ingredients: coumarin,
      hydroquinone and caffeine is shown in this study. In particular, the oral no
      observed-adverse-effect-level (NOAEL) doses of these chemicals are extrapolated
      to their corresponding dermal values by comparing the internal concentrations
      resulting from oral and dermal exposure scenarios. The PBTK model structure has
      been constructed to give a good simulation performance of biochemical processes
      within the human body. The model parameters are calibrated based on oral and
      dermal experimental data for the Caucasian population available in the
      literature. Particular attention is given to modelling the absorption stage (skin
      and gastrointestinal tract) in the form of several sub-compartments. This gives
      better model prediction results when compared to those of a PBTK model with a
      simpler structure of the absorption barrier. In addition, the role of
      quantitative structure-property relationships (QSPRs) in predicting skin
      penetration is evaluated for the three substances with a view to incorporating
      QSPR-predicted penetration parameters in the PBTK model when experimental values
      are lacking. Finally, PBTK modelling is used, first to extrapolate oral NOAEL
      doses derived from rat studies to humans, and then to simulate internal
      systemic/liver concentrations - Area Under Curve (AUC) and peak concentration -
      resulting from specified dermal and oral exposure conditions. Based on these
      simulations, AUC-based dermal thresholds for the three case study compounds are
      derived and compared with the experimentally obtained oral threshold (NOAEL)
      values. 

PMID- 24731973
TI  - In vitro metabolism of cis- and trans-permethrin by rat liver microsomes, and its
      effect on estrogenic and anti-androgenic activities.
AB  - Permethrin is a widely applied broad-spectrum pyrethroid insecticide that
      consists of a mixture of cis- and trans-isomers. We examined the changes of
      estrogenic and anti-androgenic activities resulting from metabolism of the
      isomers. Both cis- and trans-permethrin were hydrolyzed to 3-phenoxybenzyl
      alcohol (PBAlc) by rat liver microsomes, but the extent of hydrolysis of trans
      permethrin was much greater than that of the cis-isomer. In the presence of
      NADPH, PBAlc was further transformed to 4'-hydroxylated PBAlc (4'-OH PBAlc), 3
      phenoxybenzaldehyde (PBAld) and 3-phenoxybenzoic acid (PBAcid). cis-Permethrin,
      but not trans-permethrin, also afforded its 4'-hydroxylated derivative (4'-OH cis
      permethrin). trans-Permethrin was an anti-androgen, but also showed weak
      estrogenic activity, while cis-permethrin was a weak estrogen and a weak anti
      androgen. After incubation with rat liver microsomes in the presence of NADPH,
      cis-permethrin but not trans-permethrin was metabolically activated for
      estrogenic activity. On the other hand, estrogenic activity of trans-permethrin
      was not changed, but its anti-androgenic activity was enhanced after incubation.
      4'-OH PBAlc and PBAlc showed estrogenic activity, while PBAld and PBAlc showed
      anti-androgenic activity. PBAcid showed neither activity. 4'-OH cis-permethrin
      showed both estrogenic and anti-androgenic activities. Overall, our results
      indicate that permethrin is metabolically activated for estrogenic and anti
      androgen activities, and the microsomal transformation of permethrin to 4'-OH cis
      permethrin, 4'-OH PBAlc and PBAlc contributes to the both metabolic activations. 

PMID- 24731974
TI  - Clinical profile of Brugada syndrome in Hong Kong Chinese population.

PMID- 24731975
TI  - Dedicated two-stent technique in complex bifurcation percutaneous coronary
      intervention with use of everolimus-eluting stents: the EES-bifurcation study.
AB  - OBJECTIVES: To compare the outcomes of initial one-stent (1S) versus dedicated
      two-stent (2S) strategies in complex bifurcation percutaneous coronary
      intervention (PCI) using everolimus-eluting stents (EES). BACKGROUND: PCI of true
      bifurcation lesions is technically challenging and historically associated with
      reduced procedural success and increased restenosis. Prior studies comparing
      initial one-stent (1S) versus dedicated two-stent (2S) strategies using first
      generation drug-eluting stents have shown no reduction in ischemic events and
      more complications with a 2S strategy. METHODS: We performed a retrospective
      study of 319 consecutive patients undergoing PCI at a single referral center with
      EES for true bifurcation lesions, defined by involvement of both the main vessel
      (MV) and side branch (SB). Baseline, procedural characteristics, quantitative
      coronary angiography and clinical outcomes in-hospital and at one year were
      compared for patients undergoing 1S (n=175) and 2S (n=144) strategies. RESULTS:
      Baseline characteristics were well-matched. 2S strategy was associated with
      greater SB acute gain (0.65+/-0.41 mm vs. 1.11+/-0.47 mm, p<0.0001). In-hospital
      serious adverse events were similar (9% with 2S vs. 8% with 1S, p=0.58). At one
      year, patients treated by 2S strategy had non-significantly lower rates of target
      vessel revascularization (5.8% vs. 7.4%, p=0.31), myocardial infarction (7.8% vs.
      12.2%, p=0.31) and major adverse cardiovascular events (16.6% vs. 21.8%, p=0.21).
      CONCLUSION: In this study of patients undergoing PCI for true coronary
      bifurcation lesions using EES, 2S strategy was associated with superior SB
      angiographic outcomes without excess complications or ischemic events at one
      year.

PMID- 24731976
TI  - Post-cardiac injury syndrome after permanent electronic cardiac device
      implantation. Incidence, presentation, management and long-term prognosis.

PMID- 24731977
TI  - Exercise induced changes in VEGF and NT-proBNP and relationship to exercise
      induced ischemia.

PMID- 24731978
TI  - Sarcopenia, cachexia and aging: diagnosis, mechanisms and therapeutic options - a
      mini-review.
AB  - By the year 2050, individuals over the age of 65 years will comprise 20% of the
      US population. Loss of muscle mass and strength is common in this age group and
      it is associated with increased dependence, frailty and mortality. Sarcopenia,
      defined as the loss of muscle mass and function associated with aging, and
      cachexia, defined as weight loss due to an underlying illness, are muscle wasting
      disorders of particular relevance in the aging population, but they go largely
      unrecognized. In this review we highlight the common pathophysiological
      mechanisms underlying muscle loss in sarcopenia and cachexia, the factors unique
      to each condition and means of diagnosing and differentiating them clinically.
      Therapeutic options including exercise, nutritional therapy, androgens and growth
      hormone as well as their practical limitations are discussed. We also shed light
      on newer agents being developed as potential therapeutic options for wasting
      diseases.

PMID- 24731979
TI  - Low-energy cross-section calculations of single molecules by electron impact: a
      classical Monte Carlo transport approach with quantum mechanical description.
AB  - The present state of modeling radio-induced effects at the cellular level does
      not account for the microscopic inhomogeneity of the nucleus from the non-aqueous
      contents (i.e. proteins, DNA) by approximating the entire cellular nucleus as a
      homogenous medium of water. Charged particle track-structure calculations
      utilizing this approximation are therefore neglecting to account for
      approximately 30% of the molecular variation within the nucleus. To truly
      understand what happens when biological matter is irradiated, charged particle
      track-structure calculations need detailed knowledge of the secondary electron
      cascade, resulting from interactions with not only the primary biological
      component-water--but also the non-aqueous contents, down to very low energies.
      This paper presents our work on a generic approach for calculating low-energy
      interaction cross-sections between incident charged particles and individual
      molecules. The purpose of our work is to develop a self-consistent computational
      method for predicting molecule-specific interaction cross-sections, such as the
      component molecules of DNA and proteins (i.e. nucleotides and amino acids), in
      the very low-energy regime. These results would then be applied in a track
      structure code and thereby reduce the homogenous water approximation. The present
      methodology-inspired by seeking a combination of the accuracy of quantum
      mechanics and the scalability, robustness, and flexibility of Monte Carlo methods
      begins with the calculation of a solution to the many-body Schrodinger equation
      and proceeds to use Monte Carlo methods to calculate the perturbations in the
      internal electron field to determine the interaction processes, such as
      ionization and excitation. As a test of our model, the approach is applied to a
      water molecule in the same method as it would be applied to a nucleotide or amino
      acid and compared with the low-energy cross-sections from the GEANT4-DNA physics
      package of the Geant4 simulation toolkit for the energy ranges of 7 eV to 1 keV. 

PMID- 24731980
TI  - Distinctive RNA expression profiles in blood associated with Alzheimer disease
      after accounting for white matter hyperintensities.
AB  - BACKGROUND: Defining the RNA transcriptome in Alzheimer Disease (AD) will help
      understand the disease mechanisms and provide biomarkers. Though the AD blood
      transcriptome has been studied, effects of white matter hyperintensities (WMH)
      were not considered. This study investigated the AD blood transcriptome and
      accounted for WMH. METHODS: RNA from whole blood was processed on whole-genome
      microarrays. RESULTS: A total of 293 probe sets were differentially expressed in
      AD versus controls, 5 of which were significant for WMH status. The 288 AD
      specific probe sets classified subjects with 87.5% sensitivity and 90.5%
      specificity. They represented 188 genes of which 29 have been reported in prior
      AD blood and 89 in AD brain studies. Regulated blood genes included MMP9, MME
      (Neprilysin), TGFbeta1, CA4, OCLN, ATM, TGM3, IGFR2, NOV, RNF213, BMX, LRRN1,
      CAMK2G, INSR, CTSD, SORCS1, SORL1, and TANC2. CONCLUSIONS: RNA expression is
      altered in AD blood irrespective of WMH status. Some genes are shared with AD
      brain.

PMID- 24731982
TI  - Visit-to-visit blood pressure variability in Alzheimer disease.
AB  - The aim of this study was to evaluate visit-to-visit blood pressure (BP)
      variability in a cohort of patients with Alzheimer disease (AD) and healthy
      controls. Patients with clinically diagnosed mild or moderate AD and cognitively
      normal controls matched for age and sex were recruited and followed up for 6
      months. To characterize the BP status of each individual, mean, maximum and
      minimum values, SD, and coefficient of variation were obtained for both systolic
      BP (SBP) and diastolic BP (DBP). Seventy AD patients and 140 controls were
      enrolled. No meaningful differences were found in prevalence or treatments of
      various vascular risk factors. AD patients had higher maximum and lower minimum
      values and greater SD and coefficient of variation of both SBP and DBP. Group
      differences in mean values were significant only for SBP. In the multiple
      logistic regression analysis, adjusted for confounding variables, all the indices
      related to BP variability were significantly associated with AD. Our results show
      that AD patients have a greater variability of both SBP and DBP in comparison
      with age-matched cognitive normal controls, suggesting potential implication in
      the pathogenesis or progression of the disease. 

PMID- 24731981
TI  - Intracranial stenosis, cerebrovascular diseases, and cognitive impairment in
      chinese.
AB  - Extracranial carotid artery disease has been shown to be related to cognitive
      deficits. However, limited data are available on intracranial stenosis (ICS) and
      cognitive impairment. We investigate the association between ICS and cognitive
      impairment in Chinese. Subjects (n=278), recruited from the Epidemiology of
      Dementia in Singapore Study, underwent comprehensive clinical evaluation,
      neuropsychological testing, and brain magnetic resonance imaging (MRI), including
      3-dimensional-time-of-flight magnetic resonance angiography (MRA). Cognitive
      function was expressed as composite and domain-specific Z-scores. Cognitive
      impairment no dementia and dementia were diagnosed according to internationally
      accepted diagnostic criteria. Linear and logistic regression models were adjusted
      for age, sex, education, vascular risk factors, and other MRI markers. A total of
      29 (10.4%) persons had ICS on MRA, which was significantly associated with both
      composite cognitive Z-scores [mean difference in Z-score, presence vs. absence of
      ICS: -0.37 (95% confidence interval: -0.63, -0.12)] and specific domains
      including executive function, language, visuomotor speed, verbal memory, and
      visual memory. ICS was also related to significant cognitive impairment (odds
      ratio: 5.10 [1.24 to 21.02]). With respect to other MRI markers, adjusted for the
      presence of lacunar infarcts, the associations of ICS with both composite and
      domain-specific Z-scores, and significant cognitive impairment became
      nonsignificant; however, adjustment for other MRI markers did not alter these
      associations. In this Chinese population, presence of ICS was associated with
      cognitive impairment independent of vascular risk factors. These associations may
      be mediated through the presence of infarcts. 

PMID- 24731983
TI  - Bronchial thermoplasty for asthma: evidence is lacking.

PMID- 24731984
TI  - Five withanolides from the leaves of Datura metel L. and their inhibitory effects
      on nitric oxide production.
AB  - Four new withanolides named dmetelins A-D (compounds 1-4), along with the known
      compound 7alpha,27-dihydroxy-1-oxo-witha-2,5,24-trienolide (5) were isolated from
      the leaves of Datura metel L. (Solanaceae). Their structures were elucidated on
      the basis of detailed analysis of 1D and 2D NMR and mass spectrometry data. All
      the compounds were evaluated for their inhibitory effects on lipopolysaccharide
      (LPS)-induced nitric oxide (NO) production in RAW264.7 cells. Compounds 1, 4 and
      5 showed significant inhibitory activities, and compounds 2 and 3 showed moderate
      inhibitory activities with IC50 values of 17.8, 11.6, 14.9, 33.3 and 28.6 MUM,
      respectively. 

PMID- 24731985
TI  - Seasonal variation of the chemical composition and antimicrobial and cytotoxic
      activities of the essential oils from Inga laurina (Sw.) Willd.
AB  - The seasonal chemical composition of essential oils from Inga laurina was
      determined by GC/MS. In the stem bark's essential oil extracted during the dry
      season, the presence of terpenoids (30.05%) stood out, and phytol (9.76%) was the
      major compound identified. For the stem bark oil obtained during the rainy
      season, in addition to terpenoids (26.63%), a large amount of fatty acids
      (46.84%) were identified, in particular palmitic acid (25.40%). Regarding the
      leaves' essential oil obtained in the dry season, esters (42.35%) were the main
      components. The main ester present was (Z)-hex-3-enyl benzoate (10.15%) and the
      major compound of this oil was (Z)-hex-3-en-1-ol (14.23%). Terpenoids (33.84%),
      long-chain alkanes (27.04%) and fatty acids (21.72%) were the main components of
      the essential oil from leaves in the rainy season. Phytol (33.21%), nonacosane
      (21.95%) and palmitic acid (15.20%) were the major compounds identified. The
      antimicrobial activity against aerobic and anaerobic oral bacteria was evaluated
      by the microdilution broth method and cytotoxic activity was carried out with
      Vero cells. The essential oils from the rainy season showed a better inhibition
      of the bacterial growth with Minimal Inhibitory Concentrations (MIC) values of 25
      or 50 ug.mL-1 for aerobic bacteria, and high selectivity against bacteria was
      observed. The large amount of fatty acids in rainy season oils may be related to
      the better inhibitory effects observed.

PMID- 24731986
TI  - MALDI-TOF MS analysis of cellodextrins and xylo-oligosaccharides produced by
      hindgut homogenates of Reticulitermes santonensis.
AB  - Hindgut homogenates of the termite Reticulitermes santonensis were incubated with
      carboxymethyl cellulose (CMC), crystalline celluloses or xylan substrates.
      Hydrolysates were analyzed with matrix-assisted laser desorption/ionization
      coupled to time-of-flight mass spectrometry (MALDI-TOF MS). The method was first
      set up using acid hydrolysis analysis to characterize non-enzymatic profiles.
      Commercial enzymes of Trichoderma reesei or T. longibrachiatum were also tested
      to validate the enzymatic hydrolysis analysis. For CMC hydrolysis, data
      processing and visual display were optimized to obtain comprehensive profiles and
      allow rapid comparison and evaluation of enzymatic selectivity, according to the
      number of substituents of each hydrolysis product. Oligosaccharides with degrees
      of polymerization (DPs) ranging from three to 12 were measured from CMC and the
      enzymatic selectivity was demonstrated. Neutral and acidic xylo-oligosaccharides
      with DPs ranging from three to 11 were measured from xylan substrate. These
      results are of interest for lignocellulose biomass valorization and demonstrated
      the potential of termites and their symbiotic microbiota as a source of
      interesting enzymes for oligosaccharides production. 

PMID- 24731987
TI  - In vitro antioxidant and cytotoxic activity of some synthetic riparin-derived
      compounds.
AB  - This study aimed to study the in vitro antioxidant activity and cytotoxicity on
      tumor cells lines of six synthetic substances derived from riparins. All the
      substances showed antioxidant activity and riparins C, D, E, F presented cell
      growth inhibition rates greater than 70%, suggesting that these molecules have
      antitumor properties. These substances also caused greater than 80% releases of
      cytoplasmic lactate dehydrogenase enzyme (LDH). Although the antioxidant and
      antitumor properties presented herein require further assessment, the outcomes
      indicate that these novel riparins are promising biologically active compounds. 

PMID- 24731988
TI  - Acquired pellicle as a modulator for dental erosion.
AB  - Dental erosion is a multifactorial condition that can result in the loss of tooth
      structure and function, potentially increasing tooth sensitivity. The exposure of
      enamel to acids from non-bacterial sources is responsible for the progression of
      erosion. These erosive challenges are counteracted by the anti-erosive properties
      of the acquired pellicle (AP), an integument formed in vivo as a result of
      selective adsorption of salivary proteins on the tooth surface, containing also
      lipids and glycoproteins. This review provides an in-depth discussion regarding
      how the physical structure of the AP, along with its composition, contributes to
      AP anti-erosive properties. The physical properties that contribute to AP
      protective nature include pellicle thickness, maturation time, and site of
      development. The pellicle contains salivary proteins embedded within its
      structure that demonstrate anti-erosive properties; however, rather than
      individual proteins, protein-protein interactions play a fundamental role in the
      protective nature of the AP. In addition, dietary and synthetic proteins can
      modify the pellicle, enhancing its protective efficiency against dental erosion.
      The salivary composition of the AP and its corresponding protein-profile may be
      employed as a diagnostic tool, since it likely contains salivary biomarkers for
      oral diseases that initiate at the enamel surface, including dental erosion.
      Finally, by modifying the composition and structure of the AP, this protein
      integument has the potential to be used as a target-specific treatment option for
      oral diseases related to tooth demineralization.

PMID- 24731989
TI  - Lymphohematopoietic cancers induced by chemicals and other agents and their
      implications for risk evaluation: An overview.
AB  - Lymphohematopoietic neoplasia are one of the most common types of cancer induced
      by therapeutic and environmental agents. Of the more than 100 human carcinogens
      identified by the International Agency for Research on Cancer, approximately 25%
      induce leukemias or lymphomas. The objective of this review is to provide an
      introduction into the origins and mechanisms underlying lymphohematopoietic
      cancers induced by xenobiotics in humans with an emphasis on acute myeloid
      leukemia, and discuss the implications of this information for risk assessment.
      Among the agents causing lymphohematopoietic cancers, a number of patterns were
      observed. Most physical and chemical leukemia-inducing agents such as the
      therapeutic alkylating agents, topoisomerase II inhibitors, and ionizing
      radiation induce mainly acute myeloid leukemia through DNA-damaging mechanisms
      that result in either gene or chromosomal mutations. In contrast, biological
      agents and a few immunosuppressive chemicals induce primarily lymphoid neoplasms
      through mechanisms that involve alterations in immune response. Among the
      environmental agents examined, benzene was clearly associated with acute myeloid
      leukemia in humans, with increasing but still limited evidence for an association
      with lymphoid neoplasms. Ethylene oxide and 1,3-butadiene were linked primarily
      to lymphoid cancers. Although the association between formaldehyde and leukemia
      remains controversial, several recent evaluations have indicated a potential link
      between formaldehyde and acute myeloid leukemia. The four environmental agents
      examined in detail were all genotoxic, inducing gene mutations, chromosomal
      alterations, and/or micronuclei in vivo. Although it is clear that rapid progress
      has been made in recent years in our understanding of leukemogenesis, many
      questions remain for future research regarding chemically induced leukemias and
      lymphomas, including the mechanisms by which the environmental agents reviewed
      here induce these diseases and the risks associated with exposures to such
      agents.

PMID- 24731991
TI  - Emerging role of SGT1 as a regulator of NB-LRR-receptor nucleocytoplasmic
      partitioning.
AB  - Plant nucleotide-binding (NB) and leucine-rich repeat (LRR) receptors mediate
      effector-triggered immunity. Two major classes of NB-LRR proteins are involved in
      this process, namely, toll-interleukin receptor (TIR)-NB-LRR and coiled coil (CC)
      NB-LRR proteins. Recent reports show that some of the TIR-NB-LRRs and CC-NB-LRRs
      localize to the cytoplasm and nucleus. Equilibrium between these pools is
      required for full resistance, suggesting tight regulation of nucleocytoplasmic
      receptor shuttling. We recently showed that SGT1, a protein that controls NB-LRR
      receptor stability and activity, facilitates nuclear import of N protein, which
      is a TIR-NB-LRR receptor. In this addendum, we show that the subcellular
      localization of Rx, a CC-NB-LRR protein, reflects the positions of SGT1 ectopic
      variants in the cell. This suggests that SGT1 might have a general role in
      maintaining the nucleocytoplasmic balance of NB-LRR receptors. We discuss these
      results in light of differences in the N and Rx systems of effector-triggered
      immunity.

PMID- 24731990
TI  - Vaccinia-related kinase 1 (VRK1) confers resistance to DNA-damaging agents in
      human breast cancer by affecting DNA damage response.
AB  - Vaccinia-related kinase 1 (VRK1) belongs to a group of sixteen kinases associated
      to a poorer prognosis in human breast carcinomas, particularly in estrogen
      receptor positive cases based on gene expression arrays. In this work we have
      studied the potential molecular mechanism by which the VRK1 protein can
      contribute to a poorer prognosis in this disease. For this aim it was first
      analyzed by immunohistochemistry the VRK1 protein level in normal breast and in
      one hundred and thirty six cases of human breast cancer. The effect of VRK1 to
      protect against DNA damage was determined by studying the effect of its knockdown
      on the formation of DNA repair foci assembled on 53BP1 in response to treatment
      with ionizing radiation or doxorubicin in two breast cancer cell lines. VRK1
      protein was detected in normal breast and in breast carcinomas at high levels in
      ER and PR positive tumors. VRK1 protein level was significantly lower in ERBB2
      positive cases. Next, to identify a mechanism that can link VRK1 to poorer
      prognosis, VRK1 was knocked-down in two breast cancer cell lines that were
      treated with ionizing radiation or doxorubicin, both inducing DNA damage. Loss of
      VRK1 resulted in reduced formation of DNA-damage repair foci complexes assembled
      on the 53BP1 scaffold protein, and this effect was independent of damaging agent
      or cell type. This observation is consistent with detection of high VRK1 protein
      levels in ER and PR positive breast cancers. We conclude that VRK1 can contribute
      to make these tumors more resistant to DNA damage-based therapies, such as
      ionizing radiation or doxorubicin, which is consistent with its association to a
      poor prognosis in ER positive breast cancer. VRK1 is potential target kinase for
      development of new specific inhibitors which can facilitate sensitization to
      other treatments in combination therapies; or alternatively be used as a new
      cancer drugs. 

PMID- 24731993
TI  - Association of age and BP variability with long-term mortality in hemodialysis
      patients.
AB  - BACKGROUND/AIMS: Blood pressure (BP) variability is known as a poor prognostic
      factor for cardiovascular outcomes. This study assessed the prognostic
      significance of BP variability in association with increasing age in hemodialysis
      patients. METHODS: We retrospectively analyzed 2,174 patients on hemodialysis
      from March 2005 to December 2012. The impact of intradialytic and interdialytic
      BP variability on all-cause mortality according to age groups was analyzed.
      RESULTS: Kaplan-Meier survival curves for 5-year cumulative mortality showed
      higher mortality in patients with higher intradialytic systolic and diastolic BP
      variability as well as interdialytic systolic and diastolic BP variability (log
      rank p=0.006, <0.001, 0.018 and < 0.001) in patients aged <55 years, but not in
      older age groups. Cox proportional analysis revealed that 5-year mortality was
      associated with intradialytic diastolic BP variability in patients aged <55 years
      (HR, 2.03 CI, 1.24-3.32). CONCLUSION: The overall mortality was associated with
      BP variability in patients aged <55 years, but not in older ages. This result
      suggests that younger hemodialysis patients with BP variability require further
      medical attention and intervention to reduce BP variability.

PMID- 24731992
TI  - Rodent models for compulsive alcohol intake.
AB  - Continued seeking and drinking of alcohol despite adverse legal, health,
      economic, and societal consequences is a central hallmark of human alcohol use
      disorders. This compulsive drive for alcohol, defined by resistance to adverse
      and deleterious consequences, represents a major challenge when attempting to
      treat alcoholism clinically. Thus, there has long been interest in developing pre
      clinical rodent models for the compulsive drug use that characterizes drug
      addiction. Here, we review recent studies that have attempted to model compulsive
      aspects of alcohol and cocaine intake in rodents, and consider technical and
      conceptual issues that need to be addressed when trying to recapitulate
      compulsive aspects of human addiction. Aversion-resistant alcohol intake has been
      examined by pairing intake or seeking with the bitter tastant quinine or with
      footshock, and exciting recent work has used these models to identify
      neuroadaptations in the amygdala, cortex, and striatal regions that promote
      compulsive intake. Thus, rodent models do seem to reflect important aspects of
      compulsive drives that sustain human addiction, and will likely provide critical
      insights into the molecular and circuit underpinnings of aversion-resistant
      intake as well as novel therapeutic interventions for compulsive aspects of
      addiction. 

PMID- 24731994
TI  - Prostate cancer: preventing metastasis to bone: is this the end of the story?
AB  - A new report of zoledronic acid in men with high-risk prostate cancer is the
      latest in a long line of negative studies that have addressed the prevention of
      metastasis. We must learn from these studies so that potentially useful agents
      are not discarded due to poor trial design in the future.

PMID- 24731995
TI  - Kidney cancer: in crossover study, patients and physicians prefer pazopanib.

PMID- 24731996
TI  - Bladder cancer: genetic variants modify risks of recurrence and survival.

PMID- 24731997
TI  - Prostate cancer: validated tool predicts survival of men taking abiraterone after
      docetaxel.

PMID- 24731998
TI  - Expression and localization of glucose transporters in rodent submandibular
      salivary glands.
AB  - BACKGROUND/AIM: The submandibular gland is one of the three major salivary
      glands, producing a mixed secretion; this saliva is hypotonic compared to plasma.
      It also secretes glucose, but the mechanisms responsible for this process are
      poorly understood. Our study addressed the question whether glucose transporters
      are expressed and how are they localized within specific rodent submandibular
      cells, in order to estimate a possible implication in salivary glucose disposal.
      METHODS: Immunohistochemistry, RT-qPCR and Western blotting were performed to
      determine the presence/localization of glucose transporters in rodent
      submandibular glands. RESULTS: GLUT4 was identified in the submandibular salivary
      gland at both mRNA and protein level. The immunohistochemical analysis revealed
      its localization preponderantly in the ductal cells of the gland, near to the
      basolateral. SGLT1 and GLUT1 were highly expressed in submandibular tissues in
      both acinar and ductal cells, but not GLUT2. These results were confirmed by RT
      qPCR. It was also documented that insulin stimulates the net uptake of D-glucose
      by ductal rings prepared from submandibulary salivary glands, the relative
      magnitude of such an enhancing action being comparable to that found in
      hemidiaphragms. CONCLUSION: At least three major glucose transporters are
      expressed in the rodent submandibular glands, of which GLUT4 is specifically
      localized near the basolateral side of ductal structures. This points-out its
      possible role in regulating glucose uptake from the bloodstream, most likely to
      sustain ductal cellular metabolism.

PMID- 24731999
TI  - Comparison of chromatin epigenetic modification patterns among root meristem,
      elongation and maturation zones in maize (Zea mays L.).
AB  - Plant roots mainly consist of division, elongation and maturation regions.
      Histone modifications of chromatin play a vital role in plant cell growth and
      differentiation. However, there has been no systematic attempt to investigate the
      distribution patterns of histone modifications in the different plant root zones.
      In this study, histone H3 acetylation (H3K9ac), histone H4 acetylation (H4K5ac),
      and histone H3 methylation (H3K4me2, H3K4me3, H3K9me1, H3K9me2, and H3K27me2)
      levels and distribution patterns were examined in the root meristem, elongation
      and maturation zones of maize primary roots. Overall, the cells of the maturation
      zone displayed the highest level of multiple histone modifications. The lowest
      level of histone modification was detected in the root meristem. H3K9ac was
      enriched in the euchromatin and nucleoli of most nuclei from the elongation and
      maturation zones. The nucleoli of more than 60% of cells from all root regions
      were labeled by H4K5ac. In only a small proportion of cells (less than 7%), knobs
      showed H4K5ac signals. H3K4me2 and H3K4me3 were specifically detected in
      euchromatin. H3K9me1, H3K9me2 and H3K27me2 labeled heterochromatin and
      euchromatin in all the root tissues analyzed. Over 30% of elongation and
      maturation cells exhibited H3K9me1 signals around knobs, approximately 5% of
      maturation cells showed signals of H3K9me2 around knobs, and H3K27me2 was stained
      weakly in approximately 95% of maturation cells in knobs. Analysis of the genomic
      patterns of histone modifications across functionally distinct regions of maize
      roots reveals a root zone-specific chromatin distribution.

PMID- 24732000
TI  - Active sacral neuromodulator during pregnancy: a unique case report.
AB  - Sacral neuromodulation with an implanted device is used in patients who
      experience urinary retention and malfunctioning overactive bladder where
      conservative treatment is not sufficient. The knowledge of its effect on
      pregnancy is not known. This article presents the case of a 34-year-old pregnant
      woman with an implanted device, the use of which was not discontinued during her
      pregnancy. Full-term pregnancy was achieved, and a healthy child was delivered by
      cesarean section. Sacral neuromodulation during pregnancy appears to be safe and
      may be preferable to intermittent bladder catheterizations that increase the
      chance of urinary infections. 

PMID- 24732001
TI  - Prediction of postoperative pain after gynecologic laparoscopy for nonacute
      pelvic pain.
AB  - OBJECTIVE: The primary objectives of this study were to explore the pain
      experience after gynecologic laparoscopy that is performed for nonacute pain
      conditions and to determine whether preoperative psychologic tests and
      quantitative tests of sensitization can predict postoperative pain. STUDY DESIGN:
      Participants included 61 women who underwent laparoscopy for nonacute pain (n =
      61). A second group of 16 women who had undergone tubal ligation was included to
      explore whether laparoscopy induced a painful postoperative response in women
      without preoperative pain. Subjective tests included numeric pain scale, pain
      catastrophizing scale, depression scale, global assessment of change, and the
      McGill Pain Questionnaire Short Form. Quantitative sensory testing included
      abdominal cutaneous allodynia, trigger points, and reduced pain thresholds. The
      nonacute pain sample had 80% power to detect a difference of 0.5 standard
      deviation in average pain levels. Analysis included parametric and nonparametric
      comparisons of groups and univariate and linear regression analysis of clinically
      relevant variables. RESULTS: In women who underwent tubal ligation, pain levels
      were low before and after the procedure. In women who underwent surgery for
      nonacute pain, pain levels at 6 months and all psychologic test scores were
      reduced significantly compared with baseline (P < .001 and P = .001,
      respectively). Among those women with positive results on the quantitative pain
      tests of sensitization at baseline, average postoperative pain was also
      significantly reduced (P < .001). Univariate analysis demonstrated only tests of
      sensitization that were correlated with change in average pain level (P = .01).
      Regression analysis suggested that baseline pain, catastrophizing, and the
      presence of cutaneous allodynia significantly predicted pain levels 6 months
      after surgery (P < .001). CONCLUSION: Pain after laparoscopic surgery for
      nonacute painful conditions can be predicted by baseline pain, catastrophizing,
      and the presence of allodynia, which is a simple swab test that indicates
      sensitization.

PMID- 24732002
TI  - When courts intervene: public health, legal and ethical issues surrounding HIV,
      pregnant women, and newborn infants.
AB  - Ninety-three percent of pediatric AIDS cases are the result of perinatal HIV
      transmission, a disease that is almost entirely preventable with early
      intervention, which reduces the risk of perinatal HIV infection from 25% to <2%.
      The American College of Obstetricians and Gynecologists and the American Academy
      of Pediatrics both recommend routine HIV testing of all pregnant women and at
      risk newborn infants. When pregnant women decline HIV testing and/or treatment,
      public health, legal, and ethical dilemmas can result. Federal courts
      consistently uphold a woman's right to refuse medical testing and treatment, even
      though it may benefit her fetus/newborn infant. Federal courts also reliably
      respect the rights of parents to make health care decisions for their newborn
      infants, which may include declining medical testing and treatment. Confusing the
      issue of HIV testing and treatment, however, is the fact that there is no
      definitive United States Supreme Court ruling on the issue. State laws and
      standards vary widely and serve as guiding principles for practicing clinicians,
      who must be vigilant of ongoing legal challenges and changes in the states in
      which they practice. We present a case of an HIV-positive pregnant woman who
      declined treatment and then testing or treatment of her newborn infant.
      Ultimately, the legal system intervened. Given the rarity of such cases, we use
      this as a primer for the practicing clinician to highlight the public health,
      legal, and ethical issues surrounding prenatal and newborn infant HIV testing and
      treatment in the United States, including summarizing key state-to-state
      regulatory differences. 

PMID- 24732003
TI  - Ultrasound-guided instrumental removal of the retained placenta after vaginal
      delivery.
AB  - The standard treatment for retained placenta is manual extraction, in which a
      hand is introduced inside the uterus to cleave a plane between the placenta and
      the uterine wall. For women without an epidural, the procedure is extremely
      uncomfortable and may require additional measures such as intravenous narcotics
      or regional anesthesia. Although ultrasound-guided instrumental removal of the
      placenta is standard practice as part of second-trimester abortion by dilation
      and evacuation and may be done at many institutions, especially after failed
      manual extraction, it has not yet been described in the literature as a technique
      following vaginal birth. Our experience with this technique is that it causes
      less discomfort to the patient than a traditional manual extraction, because the
      instrument entering the uterus is much narrower than a hand. With the patient in
      dorsal lithotomy, we locate the cervix and stabilize it either with fingers or a
      ring forceps on the anterior lip. We introduce Bierer ovum forceps into the
      uterus under direct ultrasound guidance. The Bierer forceps are preferred because
      of their long length, large head, and serrated teeth that allow for a firm,
      secure grip on the placenta. We grasp the placental tissue with the forceps and
      apply slow, gentle traction in short strokes, regrasping increasingly more distal
      areas of placenta as necessary to tease out the placenta. After 1-2 minutes, the
      placenta separates and can be pulled out of the uterus, usually intact. Our
      experience suggests that this technique is a well-tolerated option for women
      without an epidural who have a retained placenta. Further study is needed to
      quantify the amount of discomfort and anesthesia that can be avoided with this
      technique, as well as whether there is any change in the frequency of infectious
      complications or the necessity of postremoval curettage. 

PMID- 24732004
TI  - Pure nongestational uterine choriocarcinoma in a postmenopausal Chinese woman
      confirmed with short tandem repeat analysis.
AB  - Nongestational choriocarcinomas have been observed in the ovaries but rarely the
      uterus in postmenopausal women. Choriocarcinomas of gestational and
      nongestational origin have distinct prognoses but cannot be distinguished with
      routine histologic examination. We report a case of nongestational uterine
      choriocarcinoma in a 62-year-old Chinese woman that was confirmed with short
      tandem repeat analysis. 

PMID- 24732005
TI  - Abdominal wall endometriosis: 12 years of experience at a large academic
      institution.
AB  - OBJECTIVE: The objective of the study was to review patient characteristics and
      intraoperative findings for excised cases of abdominal wall endometriosis (AWE).
      STUDY DESIGN: A 12 year medical record search was performed for cases of excised
      AWE, and the diagnosis was confirmed on pathological specimen. Descriptive data
      were collected and analyzed. RESULTS: Of 65 patients included, the primary
      clinical presentation was abdominal pain and/or a mass/lump (73.8% and 63.1%,
      respectively). Most patients had a history of cesarean section (81.5%) but 6
      patients (9.2%) had no prior surgery. Time from the initial surgery to
      presentation ranged from 1 to 32 years (median, 7.0 years), and time from the
      most recent relevant surgery ranged from 1 to 32 years (median, 4.0 years). Five
      patients (7.7%) required mesh for fascial closure following the resection of the
      AWE. We were unable to demonstrate a correlation between the increasing numbers
      of open abdominal surgeries and the time to presentation or depth of involvement.
      Age, body mass index, and parity also were not predictive of depth of
      involvement. There were increased rates of umbilical lesions (75% vs 5.6%, P <
      .001) in nulliparous compared with multiparous women as well as in women without
      a history of cesarean section (66.7% vs 1.9%, P < .001). CONCLUSION: In women
      with a mass or pain at a prior incision, the differential diagnosis should
      include AWE. Although we were unable to demonstrate specific characteristics
      predictive for AWE, a large portion of our population had a prior cesarean
      section, suggesting a correlation.

PMID- 24732006
TI  - Acidity constant and solvatochromic behavior of some pyrazolo[1,5-a]pyrimidin-2
      amine derivatives.
AB  - The UV-visible electronic spectra of some azo compounds of pyrazolo[1,5
      a]pyrimidin-2-amine have been studied. The solvatochromic behavior of these
      compounds was investigated by studying their spectra in pure organic solvents of
      different polarities such as cyclohexane carbon tetrachloride, chloroform,
      ethanol and DMF. These exhibits a red shift in its lambdamax with increase
      relative permittivity of medium changing from cyclohexane->carbon tetrachloride
      >chloroform->ethanol->DMF. The acid dissociation constants of these compounds
      were determined in aqueous-organic solvent mixtures such as acetone, methanol,
      ethanol and DMF. The ionization constants of the dyes in question depend largely
      on both the proportion and the nature of the organic solvent basicity contribute
      the major effects on the ionization process. In general, pKa values in all
      compounds decrease with increase relative permittivity of the medium. The acidity
      of studied azo compounds increases in the following order: p-NO2<m-CF3<p-F<p-Cl<p
      H<p-CH3. 

PMID- 24732007
TI  - Quantum chemical calculations on the geometrical, conformational, spectroscopic
      and nonlinear optical parameters of 5-(2-Chloroethyl)-2,4-dichloro-6
      methylpyrimidine.
AB  - The optimized geometry, (1)H and (13)C NMR chemical shifts, conformational and
      natural bond orbital (NBO) analyses, thermodynamic parameters, molecular
      surfaces, Mulliken, NBO and APT charges for 5-(2-Chloroethyl)-2,4-dichloro-6
      methylpyrimidine [C7H7Cl3N2] were investigated by the ab initio HF and density
      functional theory (DFT/B3LYP) methods with 6-311++G(d,p) basis set. The
      calculated structural parameters (bond lengths, bond angles and dihedral angles)
      and (1)H and (13)C NMR chemical shifts values are compared with experimental
      values of the investigated compound. The observed and the calculated values are
      found to be in good agreement. The energies of the highest occupied molecular
      orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) were calculated,
      and the obtained energies displayed that charge transfer occurs in 5-(2
      Chloroethyl)-2,4-dichloro-6-methylpyrimidine compound. In addition, the linear
      polarizability (alpha) and the first order hyperpolarizability (beta) values of
      the investigated compound have been computed by using HF and DFT methods. 

PMID- 24732008
TI  - Recognizing methylated histone variant H3.3 to prevent tumors.
AB  - Regulatory information stored in modified histones is functionally translated by
      effector proteins ('readers'), which identify the histone mark to determine the
      specificity of the response. A recent study identifying the tumor suppressor
      protein ZMYND11 as an exclusive reader of methylated histone variant H3.3, throws
      light on the role of transcription regulation in suppressing tumors. 

PMID- 24732010
TI  - Labeling native bacterial RNA in live cells.

PMID- 24732009
TI  - Specific control of BMP signaling and mesenchymal differentiation by cytoplasmic
      phosphatase PPM1H.
AB  - Bone morphogenetic proteins (BMPs) belong to the TGF-beta superfamily of
      structurally related signaling proteins that regulate a wide array of cellular
      functions. The key step in BMP signal transduction is the BMP receptor-mediated
      phosphorylation of transcription factors Smad1, 5, and 8 (collectively
      Smad1/5/8), which leads to the subsequent activation of BMP-induced gene
      transcription in the nucleus. In this study, we describe the identification and
      characterization of PPM1H as a novel cytoplasm-localized Smad1/5/8-specific
      phosphatase. PPM1H directly interacts with Smad1/5/8 through its Smad-binding
      domain, and dephosphorylates phospho-Smad1/5/8 (P-Smad1/5/8) in the cytoplasm.
      Ectopic expression of PPM1H attenuates BMP signaling, whereas loss of PPM1H
      activity or expression greatly enhances BMP-dependent gene regulation and
      mesenchymal differentiation. In conclusion, this study suggests that PPM1H acts
      as a gatekeeper to prevent excessive BMP signaling through dephosphorylation and
      subsequent nuclear exclusion of P-Smad1/5/8 proteins. 

PMID- 24732011
TI  - Possible leap ahead in filovirus therapeutics.
AB  - In a recent study published in Nature, Warren et al. describe the generation of a
      novel synthetic adenosine analogue, BCX4430, a synthetic drug-like small molecule
      that provides protection from Ebola and Marburg virus infection in animal models.

PMID- 24732012
TI  - Keeping the eIF2 alpha kinase Gcn2 in check.
AB  - The protein kinase Gcn2 is present in virtually all eukaryotes and is of
      increasing interest due to its involvement in a large array of crucial biological
      processes. Some of these are universally conserved from yeast to humans, such as
      coping with nutrient starvation and oxidative stress. In mammals, Gcn2 is
      important for e.g. long-term memory formation, feeding behaviour and immune
      system regulation. Gcn2 has been also implicated in diseases such as cancer and
      Alzheimer's disease. Studies on Gcn2 have been conducted most extensively in
      Saccharomyces cerevisiae, where the mechanism of its activation by amino acid
      starvation has been revealed in most detail. Uncharged tRNAs stimulate Gcn2 which
      subsequently phosphorylates its substrate, eIF2alpha, leading to reduced global
      protein synthesis and simultaneously to increased translation of specific mRNAs,
      e.g. those coding for Gcn4 in yeast and ATF4 in mammals. Both proteins are
      transcription factors that regulate the expression of a myriad of genes, thereby
      enabling the cell to initiate a survival response to the initial activating cue.
      Given that Gcn2 participates in many diverse processes, Gcn2 itself must be
      tightly controlled. Indeed, Gcn2 is regulated by a vast network of proteins and
      RNAs, the list of which is still growing. Deciphering molecular mechanisms
      underlying Gcn2 regulation by effectors and inhibitors is fundamental for
      understanding how the cell keeps Gcn2 in check ensuring normal organismal
      function, and how Gcn2-associated diseases may develop or may be treated. This
      review provides a critical evaluation of the current knowledge on mechanisms
      controlling Gcn2 activation or activity. 

PMID- 24732013
TI  - Prohibitin is involved in the activated internalization and degradation of
      protease-activated receptor 1.
AB  - The protease-activated receptor 1 (PAR1) is a G-protein-coupled receptor that is
      irreversibly activated by either thrombin or metalloprotease 1. Due this
      irrevocable activation, activated internalization and degradation are critical
      for PAR1 signaling termination. Prohibitin (PHB) is an evolutionarily conserved,
      ubiquitously expressed, pleiotropic protein and belongs to the
      stomatin/prohibitin/flotillin/HflK/C (SPFH) domain family. In a previous study,
      we found that PHB localized on the platelet membrane and participated in PAR1
      mediated human platelet aggregation, suggesting that PHB likely regulates the
      signaling of PAR1. Unfortunately, PHB's exact function in PAR1 internalization
      and degradation is unclear. In the current study, flow cytometry revealed that
      PHB expressed on the surface of endothelial cells (HUVECs) but not cancer cells
      (MDA-MB-231). Further confocal microscopy revealed that PHB dynamically
      associates with PAR1 in a time-dependent manner following induction with PAR1
      activated peptide (PAR1-AP), though differently between HUVECs and MDA-MB-231
      cells. Depletion of PHB by RNA interference significantly inhibited PAR1
      activated internalization and led to sustained Erk1/2 phosphorylation in the
      HUVECs; however, a similar effect was not observed in MDA-MB-231 cells. For both
      the endothelial and cancel cells, PHB repressed PAR1 degradation, while knockdown
      of PHB led to increased PAR1 degradation, and PHB overexpression inhibited PAR1
      degradation. These results suggest that persistent PAR1 signaling due to the
      absence of membrane PHB and decreased PAR1 degradation caused by the upregulation
      of intracellular PHB in cancer cells (such as MDA-MB-231 cells) may render cells
      highly invasive. As such, PHB may be a novel target in future anti-cancer
      therapeutics, or in more refined cancer malignancy diagnostics. 

PMID- 24732014
TI  - Oleate prevents palmitate-induced mitochondrial dysfunction, insulin resistance
      and inflammatory signaling in neuronal cells.
AB  - Elevated circulating levels of saturated free fatty acids (sFFAs; e.g. palmitate)
      are known to provoke inflammatory responses and cause insulin resistance in
      peripheral tissue. By contrast, mono- or poly-unsaturated FFAs are protective
      against sFFAs. An excess of sFFAs in the brain circulation may also trigger
      neuroinflammation and insulin resistance, however the underlying signaling
      changes have not been clarified in neuronal cells. In the present study, we
      examined the effects of palmitate on mitochondrial function and viability as well
      as on intracellular insulin and nuclear factor-kappaB (NF-kappaB) signaling
      pathways in Neuro-2a and primary rat cortical neurons. We next tested whether
      oleate preconditioning has a protective effect against palmitate-induced
      toxicity. Palmitate induced both mitochondrial dysfunction and insulin resistance
      while promoting the phosphorylation of mitogen-activated protein kinases and
      nuclear translocation of NF-kappaB p65. Oleate pre-exposure and then removal was
      sufficient to completely block subsequent palmitate-induced intracellular
      signaling and metabolic derangements. Oleate also prevented ceramide-induced
      insulin resistance. Moreover, oleate stimulated ATP while decreasing
      mitochondrial superoxide productions. The latter were associated with increased
      levels of peroxisome proliferator-activated receptor-gamma coactivator-1alpha
      (PGC-1alpha). Inhibition of protein kinase A (PKA) attenuated the protective
      effect of oleate against palmitate, implicating PKA in the mechanism of oleate
      action. Oleate increased triglyceride and blocked palmitate-induced
      diacylglycerol accumulations. Oleate preconditioning was superior to
      docosahexaenoic acid (DHA) or linoleate in the protection of neuronal cells
      against palmitate- or ceramide-induced cytotoxicity. We conclude that oleate has
      beneficial properties against sFFA and ceramide models of insulin resistance
      associated damage to neuronal cells. 

PMID- 24732015
TI  - Comparison of magnetic resonance and balloon enteroscopic examination of the
      small intestine in patients with Crohn's disease.
AB  - BACKGROUND & AIMS: Magnetic resonance (MR) enterography is a recommended imaging
      technique for detecting intestinal involvement in Crohn's disease (CD). However,
      the diagnostic accuracy of MR enterography has not been compared directly what
      that of enteroscopy of the jejunum and proximal ileum. We evaluated the
      usefulness of MR enterocolonography (MREC) by comparing its findings with those
      from balloon-assisted enteroscopy. METHODS: In a prospective study, MREC and
      enteroscopy were performed within 3 days of each other on 100 patients.
      Ulcerative lesions and all mucosal lesions were evaluated. Physicians and
      radiologists were blinded to results from other studies. Findings from MREC were
      compared directly with those from enteroscopy; the sensitivity and specificity
      with which MREC detected CD lesions were assessed. RESULTS: MREC detected
      ulcerative lesions and all mucosal lesions in the small intestine with 82.4%
      sensitivity (95% confidence interval [CI], 75.4%-87.7%) and 67.5% sensitivity
      (95% CI, 63.1%-70.0%); specificity values were 87.6% (95% CI, 83.7%-90.6%) and
      94.8% (95% CI, 90.1%-97.5%). MREC detected major stenosis with 58.8% sensitivity
      (95% CI, 37.6%-77.2%) and 90.0% specificity (95% CI, 88.4%-91.5%) and all
      stenoses with 40.8% sensitivity (95% CI, 30.8%-49.4%) and 93.7% specificity (95%
      CI, 91.1%-95.9%). CONCLUSIONS: MREC is useful for detecting active lesions in the
      small intestine. However, MR imaging is less sensitive for detecting intestinal
      damage, such as stenoses. Enteroscopy is preferred for identifying intestinal
      damage. Suitable imaging approaches should be selected to assess CD lesions in
      deep small intestine.

PMID- 24732016
TI  - Detailed distribution of lipids in GreenshellTM mussel (Perna canaliculus).
AB  - GreenshellTM mussels (GSM-Perna canaliculus) are a source of omega-3 (n-3) long
      chain polyunsaturated fatty acids (LC-PUFA). Farmed GSM are considered to be a
      sustainable source of LC-PUFA as they require no dietary inputs, gaining all of
      their oil by filter-feeding microorganisms from sea water. GSM oil is a high
      value product, with a value as much as 1000 times that of fish oils. GSM oil has
      important health benefits, for example, anti-inflammatory activity. It also
      contains several minor lipid components that are not present in most fish oil
      products, and that have their own beneficial effects on human health. We have
      shown the lipid content of the female GSM (1.9 g/100 g ww) was significantly
      greater than that of the male (1.4 g/100 g ww). Compared with male GSM, female
      GSM contained more n-3 LC-PUFA, and stored a greater proportion of total lipid in
      the gonad and mantle. The higher lipid content in the female than the male GSM is
      most likely related to gamete production. This information will be useful to
      optimize extraction of oils from GSM, a local and sustainable source of n-3 LC
      PUFA.

PMID- 24732017
TI  - Dietary pattern among schoolchildren with normal nutritional status in Navarre,
      Spain.
AB  - A nutrition survey was carried out (food intake registration of three consecutive
      school days) in a randomly selected group of 353 schoolchildren (188 males and
      165 females) with normal nutritional status. The average age of the surveyed
      students was 10.5 years (CI 95%: 10.3-11.7). There were no significant
      differences between both sexes in mean values for calorie intake (males: 2072.7
      +/- 261.7 and females: 2060.9 +/- 250.6) and intake of macronutrients, minerals
      and vitamins. Cereals (34%), dairy products (19%) and meats (17%) were
      responsible for approximately 70% of total calorie intake. Protein accounted for
      20.3% of energy intake, carbohydrates for 48.8%, total fat for 30.9%, and
      saturated fat for 12.6%. Cholesterol intake was excessive and over two-thirds of
      protein intake was from animal sources. The mean intakes of calcium, iodine and
      Vitamins A, D and E were below recommended levels. The dietary patterns of the
      schoolchildren with normal nutritional status differed from the Mediterranean
      diet. Intakes of meat were too high and dairy products and cereals consumption
      was relatively limited; while that of vegetables; legumes; fruits and fish were
      insufficient; leading to excessive protein and fat intake from animal sources and
      insufficient mineral (calcium and iodine) and Vitamins A; D and E intake. 

PMID- 24732018
TI  - Variation in gastric pH may determine kiwifruit's effect on functional GI
      disorder: an in vitro study.
AB  - Consumption of kiwifruit is reported to relieve symptoms of functional
      gastrointestinal (GI) disorder. The effect may be related to the proteases in
      kiwifruit. This in vitro study aimed to measure protein hydrolysis due to
      kiwifruit protease under gastric and duodenal conditions. A sequence of
      experiments incubated meat protein, with and without kiwifruit, with varying
      concentrations of pepsin and hydrochloric acid, at 37  degrees C for 60 min over
      the pH range 1.3-6.2 to simulate gastric digestion. Duodenal digestion was
      simulated by a further 120 min incubation at pH 6.4. Protein digestion efficiency
      was determined by comparing Kjeldahl nitrogen in pre- and post-digests. Where
      acid and pepsin concentrations were optimal for peptic digestion, hydrolysis was
      80% effective and addition of kiwifruit made little difference. When pH was
      increased to 3.1 and pepsin activity reduced, hydrolysis decreased by 75%;
      addition of kiwifruit to this milieu more than doubled protein hydrolysis. This
      in vitro study has shown, when gastric pH is elevated, the addition of kiwifruit
      can double the rate of hydrolysis of meat protein. This novel finding supports
      the hypothesis that consumption of kiwifruit with a meal can increase the rate of
      protein hydrolysis, which may explain how kiwifruit relieves functional GI
      disorder.

PMID- 24732020
TI  - An investigation of automatic exposure control calibration for chest imaging with
      a computed radiography system.
AB  - The purpose of this study was to examine the use of three physical image quality
      metrics in the calibration of an automatic exposure control (AEC) device for
      chest radiography with a computed radiography (CR) imaging system. The metrics
      assessed were signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR) and mean
      effective noise equivalent quanta (eNEQm), all measured using a uniform chest
      phantom. Subsequent calibration curves were derived to ensure each metric was
      held constant across the tube voltage range. Each curve was assessed for its
      clinical appropriateness by generating computer simulated chest images with
      correct detector air kermas for each tube voltage, and grading these against
      reference images which were reconstructed at detector air kermas correct for the
      constant detector dose indicator (DDI) curve currently programmed into the AEC
      device. All simulated chest images contained clinically realistic projected
      anatomy and anatomical noise and were scored by experienced image evaluators.
      Constant DDI and CNR curves do not appear to provide optimized performance across
      the diagnostic energy range. Conversely, constant eNEQm and SNR do appear to
      provide optimized performance, with the latter being the preferred calibration
      metric given as it is easier to measure in practice. Medical physicists may use
      the SNR image quality metric described here when setting up and optimizing AEC
      devices for chest radiography CR systems with a degree of confidence that
      resulting clinical image quality will be adequate for the required clinical task.
      However, this must be done with close cooperation of expert image evaluators, to
      ensure appropriate levels of detector air kerma. 

PMID- 24732019
TI  - Vitamin D and depression: a systematic review and meta-analysis comparing studies
      with and without biological flaws.
AB  - Efficacy of Vitamin D supplements in depression is controversial, awaiting
      further literature analysis. Biological flaws in primary studies is a possible
      reason meta-analyses of Vitamin D have failed to demonstrate efficacy. This
      systematic review and meta-analysis of Vitamin D and depression compared studies
      with and without biological flaws. The systematic review followed the Preferred
      Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The
      literature search was undertaken through four databases for randomized controlled
      trials (RCTs). Studies were critically appraised for methodological quality and
      biological flaws, in relation to the hypothesis and study design. Meta-analyses
      were performed for studies according to the presence of biological flaws. The 15
      RCTs identified provide a more comprehensive evidence-base than previous
      systematic reviews; methodological quality of studies was generally good and
      methodology was diverse. A meta-analysis of all studies without flaws
      demonstrated a statistically significant improvement in depression with Vitamin D
      supplements (+0.78 CI +0.24, +1.27). Studies with biological flaws were mainly
      inconclusive, with the meta-analysis demonstrating a statistically significant
      worsening in depression by taking Vitamin D supplements (-1.1 CI -0.7, -1.5).
      Vitamin D supplementation (>=800 I.U. daily) was somewhat favorable in the
      management of depression in studies that demonstrate a change in vitamin levels,
      and the effect size was comparable to that of anti-depressant medication.

PMID- 24732021
TI  - Recombinant hyperthermophilic enzyme expression in plants: a novel approach for
      lignocellulose digestion.
AB  - Plant biomass, as an abundant renewable carbon source, is a promising alternative
      to fossil fuels. However, the enzymes most commonly used for depolymerization of
      lignocellulosic biomass are expensive, and the development of cost-effective
      alternative conversion technologies would be desirable. One possible option is
      the heterologous expression of genes encoding lignocellulose-digesting enzymes in
      plant tissues. To overcome simultaneously issues of toxicity and incompatibility
      with high-temperature steam explosion processes, the use of heterologous genes
      encoding hyperthermophilic enzymes may be an attractive alternative. This
      approach could reduce the need for exogenous enzyme additions prior to
      fermentation, reducing the cost of the complete processing operation. This review
      highlights recent advances and future prospects for using hyperthermophilic
      enzymes in the biofuels industry. 

PMID- 24732022
TI  - Multivariate PAT solutions for biopharmaceutical cultivation: current progress
      and limitations.
AB  - Increasingly elaborate and voluminous datasets are generated by the
      (bio)pharmaceutical industry and are a major challenge for application of PAT and
      QbD principles. Multivariate data analysis (MVDA) is required to delineate
      relevant process information from large multi-factorial and multi-collinear
      datasets. Here the key role of MVDA for industrial (bio)process data is
      discussed, with a focus on progress and limitations of MVDA as a PAT solution for
      biopharmaceutical cultivation processes. MVDA based models were proven useful and
      should be routinely implemented for bioprocesses. It is concluded that although
      the highest level of PAT with process control within its design space in real
      time during manufacturing is not reached yet, MVDA will be central to reach this
      ultimate objective for cell cultivations. 

PMID- 24732024
TI  - At the bedside: adoptive cell therapy for melanoma-clinical development.
AB  - Adoptive cell therapy for melanoma, particularly using TIL, consists of a complex
      and difficult set of procedures, although it has a strong preclinical background
      and justification and has been pursued clinically by one small group of
      investigators over the last 20 years. More recent developments and a better
      understanding of the molecular basis of the anti-tumor immune response have led
      to the conduct of clinical trials that use lymphoid depletion with chemotherapy
      and/or TBI to exploit the favorable immune milieu of homeostatic lymphoid
      reconstitution during transfer of effector T cells. Improved ways of propagating
      T cells ex vivo have also simplified and shortened the cell-growth process.
      Current TIL trials have now been expanded beyond the initial center where it was
      developed, reproducing excellent objective response rates of 40-50% in previously
      treated melanoma patients and more importantly, demonstrating that a significant
      proportion of patients will be alive and free of disease 3-5 years after
      treatment, raising the possibility that those patients may be cured of their
      disease. Newer methods for growing the infiltrating T cells using immune
      checkpoint antibodies or other agents to condition the tumor before harvest and
      improved technology to simplify the complex and often cumbersome cell-growth
      process suggest that this technology may be able to be disseminated to a wide
      selection of cancer centers and may be a candidate for testing in a randomized
      Phase III trial to show definitively its benefit in patients with metastatic
      melanoma. In the accompanying review, the preclinical work that supports the idea
      of adoptive cell therapy with TIL and expands the concept in promising new ways
      will be explored. 

PMID- 24732025
TI  - Intestinal expression of the anti-inflammatory interleukin-1 homologue IL-37 in
      pediatric inflammatory bowel disease.
AB  - OBJECTIVES: The function of interleukin (IL)-37 has not been resolved. We
      recently showed that IL-37 suppresses colonic inflammation in mice. To gain more
      insight into its relevance in human disease, we investigated the expression of IL
      37 in the intestine of pediatric patients with chronic inflammatory bowel disease
      (IBD). METHODS: Intestinal biopsies were obtained from children with IBD (18
      Crohn disease [CD], 14 ulcerative colitis [UC] and 11 controls) during endoscopy
      and analyzed for IL-37 expression by immunohistochemistry and real-time
      polymerase chain reaction. Results were correlated with immunostaining for IL-18
      and IL-17, messenger RNA (mRNA) levels of pro- and anti-inflammatory cytokines,
      and clinical parameters. RESULTS: IL-37 protein was detected in epithelial cells
      and submucosal lymphoid cells of patients with CD and UC as well as healthy
      controls. IL-37 protein expression tended to be higher with submucosal lymphoid
      cell infiltration of patients with CD and UC and correlated with histological
      severity score of inflammation. IL-18 showed a staining pattern similar to that
      of IL-37, whereas staining for IL-17 revealed distinct positive cells scattered
      in the submucosal layer. mRNA expression of IL-8, IL-17, and IL-10 was
      upregulated in patients with CD and UC. mRNA levels of IL-18 and IL-37 were not
      significantly elevated compared with controls. Levels of IL-37 and IL-18 mRNA
      showed a positive correlation in the CD group. CONCLUSIONS: IL-37 protein is
      expressed in healthy and diseased bowel tissue. IL-37 and IL-18 show a similar
      expression pattern and correlate at mRNA levels. Future studies are warranted to
      delineate the specific contribution of IL-37 to modulate chronic bowel
      inflammation in humans.

PMID- 24732023
TI  - Mechanical ventilation-associated lung fibrosis in acute respiratory distress
      syndrome: a significant contributor to poor outcome.
AB  - One of the most challenging problems in critical care medicine is the management
      of patients with the acute respiratory distress syndrome. Increasing evidence
      from experimental and clinical studies suggests that mechanical ventilation,
      which is necessary for life support in patients with acute respiratory distress
      syndrome, can cause lung fibrosis, which may significantly contribute to
      morbidity and mortality. The role of mechanical stress as an inciting factor for
      lung fibrosis versus its role in lung homeostasis and the restoration of normal
      pulmonary parenchymal architecture is poorly understood. In this review, the
      authors explore recent advances in the field of pulmonary fibrosis in the context
      of acute respiratory distress syndrome, concentrating on its relevance to the
      practice of mechanical ventilation, as commonly applied by anesthetists and
      intensivists. The authors focus the discussion on the thesis that mechanical
      ventilation-or more specifically, that ventilator-induced lung injury-may be a
      major contributor to lung fibrosis. The authors critically appraise possible
      mechanisms underlying the mechanical stress-induced lung fibrosis and highlight
      potential therapeutic strategies to mitigate this fibrosis. 

PMID- 24732026
TI  - Body positioning and medical therapy for infantile gastroesophageal reflux
      symptoms.
AB  - OBJECTIVE: Proton-pump inhibitors (PPIs) reduce acid gastroesophageal reflux
      (GER) and esophageal acid exposure in infants; however, they do not reduce total
      GER or symptoms attributed to GER. Reflux is reduced in the left lateral position
      (LLP). We hypothesize that the effect of LLP in combination with acid suppression
      is most effective in reducing GER symptoms in infants. METHODS: In this
      prospective sham-controlled trial, infants (0-6 months) with symptoms suggestive
      of gastroesophageal reflux disease were studied using 8-hour pH-impedance,
      cardiorespiratory and video monitoring, direct nurse observation, and a validated
      questionnaire. Infants demonstrating a positive GER symptom association were
      randomized to 1 of 4 groups; PPI + LLP, PPI + head of cot elevation (HE), antacid
      (AA) + LLP, or AA + HE. HE and AA were considered "sham" therapies. After 2 weeks
      the 8-hour studies were repeated on-therapy. RESULTS: Fifty-one patients were
      included (aged 13.6 [2-26] weeks). PPI + LLP was most effective in reducing GER
      episodes (69 [13] to 46 [10], P < 0.001) and esophageal acid exposure (median
      [interquartile range] 8.9% [3.1%-18.1%] to 1.1% [0%-4.4%], P = 0.02). No
      treatment group showed improvement in crying/irritability, although vomiting was
      reduced in AA + LLP (from 7 [2] to 2 [0] episodes P = 0.042). LLP compared with
      HE produced greater reduction in total GER (-21 [4] vs -10 [4], P = 0.056),
      regardless of acid-suppressive therapy. Acid exposure was reduced on PPI compared
      with AA (-6.8 [2.1] vs -0.9 [1.4]%, pH < 4, P = 0.043) regardless of positional
      intervention. A post-hoc analysis using automated analysis software revealed a
      significant reduction in crying symptoms in the PPI + LLP group (99 [65-103] to
      62 [32-96] episodes, P = 0.018). CONCLUSIONS: "Symptomatic gastroesophageal
      reflux disease" implies disease causation for distressing infant symptoms. In
      infants with symptoms attributed to GER, LLP produced a significant reduction in
      total GER, but did not result in a significant improvement in symptoms other than
      vomiting; however, automated analysis appeared to identify infants with GER
      associated crying symptoms who responded to positioning therapy. This is an
      important new insight for future research.

PMID- 24732027
TI  - Spleen stiffness measurement by transient elastography to diagnose portal
      hypertension in children.
AB  - BACKGROUND: The development of esophageal varices is a late complication of
      chronic liver disease (LD) in children. The diagnosis is presently limited to
      invasive procedures such as endoscopy. Noninvasive tools to diagnose the presence
      and degree of esophageal varices would alter management decisions and support
      indications for invasive procedures in affected children. The aim of the study
      was to test the feasibility of spleen stiffness measurement (SSM) by transient
      elastography (TE; FibroScan) in children and compare data on its diagnostic use
      with established markers of liver fibrosis and parameters of portal hypertension.
      METHODS: A total of 99 children (62 with chronic LD, 6 after liver
      transplantation, 31 controls) underwent SSM by TE. Fibrotest was determined in 37
      children, 45 children had an additional liver stiffness measurement, and 19
      underwent upper endoscopy. RESULTS: SSM by FibroScan is feasible. Spleen size
      significantly determined success rate (90.5% in patients with splenomegaly vs
      70.2% in patients without, P = 0.02). Spleen stiffness was significantly higher
      in patients with splenomegaly (62.96 vs 18.4 kPa, P < 0.001), in patients with
      varices (75 vs 24 kPa, P < 0.01), and in patients with a history of variceal
      hemorrhage (75 vs 50.25 kPa, P < 0.05). Variceal hemorrhage did not occur in
      patients with SSM results <60 kPa. Spleen stiffness decreased after liver
      transplantation, but remained elevated compared with controls (27.5 vs 16.3 kPa).
      Liver stiffness measurements and Fibrotest did not reflect the presence or degree
      of esophageal varices. CONCLUSIONS: SSM by TE is feasible in children and the
      results reflect the degree and occurrence of complications. A prospective follow
      up study with larger patient numbers and performance of screening endoscopies
      appears justified and desirable.

PMID- 24732028
TI  - Distribution of polycyclic aromatic hydrocarbon (PAH) residues in several tissues
      of edible fishes from the largest freshwater lake in China, Poyang Lake, and
      associated human health risk assessment.
AB  - The residual levels, tissue distribution and human health risk assessment of
      polycyclic aromatic hydrocarbons (PAHs) in edible fishes, bighead carp
      (Aristichthys nobilis) and silver carp (Hypophthalmichthys molitrix), from the
      largest freshwater lake in China, Poyang Lake, were studied. PAH concentrations
      ranged from 105 to 513ng g(-1)ww and from 53.9 to 401ng g(-1)ww in different
      tissues of bighead carp and silver carp, respectively. Low molecular weight (LMW)
      PAHs were the predominant compounds, suggesting the gill-water transfer might be
      the major exposure route for PAHs in the studied fish species. Tissue
      distribution indicated that the hepatobiliary system accumulated higher
      concentrations of PAHs than the extrahepatic tissues with bile being the most
      predominant tissue for both species. Composition analysis demonstrated that PAHs
      were from the combined petrogenic and pyrogenic origin, and the gasoline
      combustion might be the main source. A preliminary evaluation of human health
      risk using benzo[a]pyrene (BaP) potency equivalent concentration (PEC) as well as
      the incremental lifetime cancer risk (ILCR) indicated that PAHs in fish would
      induce potential carcinogenic effects.

PMID- 24732029
TI  - Effect of cadmium on selected physiological and morphological parameters in
      metallicolous and non-metallicolous populations of Echium vulgare L.
AB  - Cadmium tolerance of three populations of Echium vulgare L., naturally occurring
      on two Zn-Pb waste deposits (metallicolous populations M1, M2) and on an
      uncontaminated site (non-metallicolous population, NM) was investigated. The
      plants were cultivated in hydroponics at 0, 5, 15, 30, or 50MUM Cd for 14 days.
      Although Cd reduced the content of photosynthetic pigments indifferently in the
      three populations, plant growth parameters and root viability analyses confirmed
      different Cd tolerances decreasing in the order M1>M2>NM in the populations
      studied. Organic acids (tartrate, malate, citrate, succinate) were not
      responsible for the elevated Cd tolerance of the metallicolous populations,
      although malate and citrate might participate in Cd detoxification in the roots
      of the M1 and M2. Phytochelatin concentrations were higher in the roots of M1 and
      M2 populations of E. vulgare, suggesting their role in Cd detoxification and
      different Cd tolerances. 

PMID- 24732030
TI  - Polycyclic aromatic hydrocarbons in road-deposited sediments, water sediments,
      and soils in Sydney, Australia: Comparisons of concentration distribution,
      sources and potential toxicity.
AB  - Sixteen polycyclic aromatic hydrocarbons (PAHs) considered as priority
      environmental pollutants were analysed in surface natural soils (NS), road
      deposited sediments (RDS), and water sediments (WS) at Kogarah in Sydney,
      Australia. Comparisons were made of their concentration distributions, likely
      sources and potential toxicities. The concentrations (mg/kg) in NS, RDS, and WS
      ranged from 0.40 to 7.49 (mean 2.80), 1.65 to 4.00 (mean 2.91), and 0.49 to 5.19
      (mean 1.76), respectively. PAHs were dominated by relatively high molecular
      weight compounds with more than three fused benzene rings, indicating that high
      temperature combustion processes were their predominant sources. The proportions
      of high molecular weight PAHs with five or six fused benzene rings were higher in
      NS than in RDS, whereas the low molecular weight PAHs were higher in RDS.
      Concentrations of all PAHs compounds were observed to be the lowest in WS. The
      concentrations of most of the high molecular weight PAHs significantly correlated
      with each other in RDS and WS. All PAHs (except naphthalene) were significantly
      correlated in NS suggesting a common PAH source. Ratios for individual diagnostic
      PAHs demonstrated that the primary source of PAHs in WS and NS was of pyrogenic
      origin (combustion of petroleum (vehicle exhaust), grass, and wood) while in RDS
      it was petrogenic (i.e. unburned or leaked fuel and oil, road asphalt, and tyre
      particles) as well as pyrogenic. The potential toxicities of PAHs calculated
      using a toxicity equivalent quotient (TEQ) were all low but higher for NS
      compared to WS and RDS. 

PMID- 24732031
TI  - Bone abnormal signal incidentally found in pre-biopsy diffusion-weighted MRI for
      suspected prostate cancer: what does it reflect?
AB  - OBJECTIVE: To clarify the clinical significance of incidentally found diffusion
      weighted MRI (DW-MRI)-positive findings on pre-biopsy MRI in patients with
      suspected prostate cancer. PATIENTS AND METHODS: 754 consecutive patients with
      suspected prostate cancer underwent pelvic MRI including DW-MRI. 43 DW-MRI
      positive bone lesions were found in 27 patients. Imaging findings of these
      lesions were compared with the clinical diagnosis. RESULTS: Of the 43 DW-MRI
      positive bone lesions, 21 (48.8%) were diagnosed as metastatic prostate cancer.
      The remaining 22 (51.2%) were diagnosed as red bone marrow in 17, enchondroma in
      1, ganglion in 1, osteoma in 1, fibrous dysplasia in 1 and bone infarction in 1.
      Enchondroma, ganglion, osteoma and fibrous dysplasia all showed T1-weighted
      imaging (T1WI) low and T2-weighted imaging (T2WI) high signals, while others,
      including prostate cancer metastases, showed T1WI and T2WI low signals. Of the 40
      lesions with T1WI and T2WI low signals, metastatic prostate cancer had higher
      apparent diffusion coefficient values (median 0.42 * 10(-3) mm(2)/s) than other
      lesions (0.26 * 10(-3) mm(2)/s; p < 0.0001). CONCLUSIONS: DW-MRI-positive bone
      lesions represent various coexisting types of bone lesions, including metastatic
      cancer in patients with suspected prostate cancer. T2WI findings and apparent
      diffusion coefficient values can be helpful in diagnosing metastatic cancer.

PMID- 24732032
TI  - Investigation of the phase transitions occurring during and after the dehydration
      of xylazine hydrochloride monohydrate.
AB  - This paper reports an investigation of a complex solid state phase transition
      where two inter-converting polymorphs (X and A) of the pharmaceutical molecule
      xylazine hydrochloride formed and transformed during and after the dehydration of
      its monohydrate (H). The crystal structures of all three forms were compared.
      During the investigation of this solid state phase transition it was determined
      that the dehydration of H produced either a pure X form, or a mixture of the X
      and A forms. The phase composition depended on the sample preparation procedure
      and the experimental conditions. It was found that grinding of the hydrate
      enhanced the formation of polymorph X as a product of dehydration, whereas higher
      humidity, temperature, or mechanical compression enhanced the formation of
      polymorph A. The transition mechanism of this complex process was analysed and
      explained by taking into account the crystal structures of these three forms. 

PMID- 24732033
TI  - Population balance modelling and multi-stage optimal control of a pulsed spray
      fluidized bed granulation.
AB  - In this work, one-dimensional population balance models (PBMs) have been
      developed to model a pulsed top-spray fluidized bed granulation. The developed
      PBMs have linked the key binder solution spray operating factors of the binder
      spray rate, atomizing air pressure and pulsed frequency of spray with the granule
      properties to predict granule growth behaviour in the pulsed spray fluidized bed
      granulation process at different operating conditions with accuracy. A multi
      stage open optimal control strategy based on the developed PBMs was proposed to
      reduce the model mismatch, in which through adjusting the trajectory of the
      evolution of the granule size distribution at predefined sample intervals, to
      determine the optimal operating variables related to the binder spray including
      the spray rate of binding liquid, atomizing air pressure and pulsed frequency of
      spray. The effectiveness of the proposed modelling and multi-stage open optimal
      control strategies has been validated by experimental and simulation tests. 

PMID- 24732034
TI  - A survey for Echinococcus spp. of carnivores in six wildlife conservation areas
      in Kenya.
AB  - To investigate the presence of Echinococcus spp. in wild mammals of Kenya, 832
      faecal samples from wild carnivores (lions, leopards, spotted hyenas, wild dogs
      and silver-backed jackals) were collected in six different conservation areas of
      Kenya (Meru, Nairobi, Tsavo West and Tsavo East National Parks, Samburu and
      Maasai Mara National Reserves). Taeniid eggs were found in 120 samples (14.4%).
      In total, 1160 eggs were isolated and further analysed using RFLP-PCR of the nad1
      gene and sequencing. 38 of these samples contained eggs of Echinococcus spp.,
      which were identified as either Echinococcus felidis (n=27) or Echinococcus
      granulosus sensu stricto (n=12); one sample contained eggs from both taxa. E.
      felidis was found in faeces from lions (n=20) and hyenas (n=5) while E.
      granulosus in faeces from lions (n=8), leopards (n=1) and hyenas (n=3). The host
      species for two samples containing E. felidis could not be identified with
      certainty. As the majority of isolated eggs could not be analysed with the
      methods used (no amplification), we do not attempt to give estimates of faecal
      prevalences. Both taxa of Echinococcus were found in all conservation areas
      except Meru (only E. felidis) and Tsavo West (only E. granulosus). Host species
      identification for environmental faecal samples, based on field signs, was found
      to be unreliable. All samples with taeniid eggs were subjected to a confirmatory
      host species RLFP-PCR of the cytochrome B gene. 60% had been correctly identified
      in the field. Frequently, hyena faeces were mistaken for lion and vice versa, and
      none of the samples from jackals and wild dogs could be confirmed in the tested
      sub-sample. This is the first molecular study on the distribution of Echinococcus
      spp. in Kenyan wildlife. The presence of E. felidis is confirmed for lions and
      newly reported for spotted hyenas. Lions and hyenas are newly recognized hosts
      for E. granulosus s.s., while the role of leopards remains uncertain. These data
      provide the basis for further studies on the lifecycles and the possible link
      between wild and domestic cycles of cystic echinococcosis in eastern Africa. 

PMID- 24732035
TI  - Binding assay between murine Dectin-1 and beta-glucan/DNA complex with quartz
      crystal microbalance.
AB  - A beta-glucan called schizophyllan (SPG) forms a stoichiometric complex with
      polynucleotides with its two main chain glucoses interacting with one nucleotide
      base. This complex can be used as a Dectin-1 targeting delivery for therapeutic
      oligonucleotides (ODN), where Dectin-1 is a membrane receptor of immunocyte cell
      that can recognize beta-glucans. Our in vivo and in vitro assays
      phenomenologically implied that such a targeting is indeed achieved. However, we
      do not know whether SPG/ODN complexes are recognized by Dectin-1. In this study,
      we examined the binding affinity between SPG/poly(dA) complex and a constructed
      protein representing the extracellular carbohydrate-recognition domain of murine
      Dectin-1 by use of quartz-crystal microbalance (QCM). It was shown that the
      SPG/dA60 complex made form phosphodiester was recognized in the same manner as
      SPG, while its dissociation constant (Kd) was much larger than SPG itself, that
      is, less affinity than SPG. When the phosphodiester linkage of dA60 was changed
      to phosphorothioate (denoted by dA60(S)), the QCM frequency decrease was
      dramatically enhanced. There seemed to be multiple binding sites; the same site
      as SPG and SPG/dA60, and an additional site (or sites) for which phosphate anion
      specific electrostatic interactions were mainly involved. Interestingly, this new
      site showed a comparable affinity with that between SPG and its original binding
      site. 

PMID- 24732036
TI  - The AHP6 cytokinin signaling inhibitor mediates an auxin-cytokinin crosstalk that
      regulates the timing of organ initiation at the shoot apical meristem.
AB  - Phyllotaxis, the spatio-temporal pattern of organogenesis at the shoot apical
      meristem, emerges in large part from inhibitory fields consisting in auxin
      depleted areas centered on organs. We recently demonstrated the existence of an
      additional hormone-based inhibitory field generated by Arabidopsis Histidine
      Phosphotransfer Protein 6 (AHP6), an inhibitor of cytokinin signaling. We have
      shown that the spatio-temporal distribution of AHP6 in the meristem is essential
      for optimizing the rhythmicity of organ initiation. Here, we further analyzed
      AHP6 expression using fluorescent whole mount mRNA in situ hybridization and
      demonstrate a precise control of AHP6 level and expression domain over time.
      While we previously showed a regulation of AHP6 directly downstream of auxin, we
      show here that AHP6 transcription is unlikely influenced by cytokinin
      distribution in the meristem. Finally, we provide evidence that cytokinins and
      auxin might act synergistically during organ initiation, providing a plausible
      explanation for how AHP6 regulates phyllotaxis.

PMID- 24732037
TI  - Network reconstruction using nonparametric additive ODE models.
AB  - Network representations of biological systems are widespread and reconstructing
      unknown networks from data is a focal problem for computational biologists. For
      example, the series of biochemical reactions in a metabolic pathway can be
      represented as a network, with nodes corresponding to metabolites and edges
      linking reactants to products. In a different context, regulatory relationships
      among genes are commonly represented as directed networks with edges pointing
      from influential genes to their targets. Reconstructing such networks from data
      is a challenging problem receiving much attention in the literature. There is a
      particular need for approaches tailored to time-series data and not reliant on
      direct intervention experiments, as the former are often more readily available.
      In this paper, we introduce an approach to reconstructing directed networks based
      on dynamic systems models. Our approach generalizes commonly used ODE models
      based on linear or nonlinear dynamics by extending the functional class for the
      functions involved from parametric to nonparametric models. Concomitantly we
      limit the complexity by imposing an additive structure on the estimated slope
      functions. Thus the submodel associated with each node is a sum of univariate
      functions. These univariate component functions form the basis for a novel
      coupling metric that we define in order to quantify the strength of proposed
      relationships and hence rank potential edges. We show the utility of the method
      by reconstructing networks using simulated data from computational models for the
      glycolytic pathway of Lactocaccus Lactis and a gene network regulating the
      pluripotency of mouse embryonic stem cells. For purposes of comparison, we also
      assess reconstruction performance using gene networks from the DREAM challenges.
      We compare our method to those that similarly rely on dynamic systems models and
      use the results to attempt to disentangle the distinct roles of linearity,
      sparsity, and derivative estimation. 

PMID- 24732038
TI  - Attenuation of pathogenic immune responses during infection with human and simian
      immunodeficiency virus (HIV/SIV) by the tetracycline derivative minocycline.
AB  - HIV immune pathogenesis is postulated to involve two major mechanisms: 1) chronic
      innate immune responses that drive T cell activation and apoptosis and 2)
      induction of immune regulators that suppress T cell function and proliferation.
      Both arms are elevated chronically in lymphoid tissues of non-natural hosts,
      which ultimately develop AIDS. However, these mechanisms are not elevated
      chronically in natural hosts of SIV infection that avert immune pathogenesis
      despite similarly high viral loads. In this study we investigated whether
      minocycline could modulate these pathogenic antiviral responses in non-natural
      hosts of HIV and SIV. We found that minocycline attenuated in vitro induction of
      type I interferon (IFN) and the IFN-stimulated genes indoleamine 2,3-dioxygenase
      (IDO1) and TNF-related apoptosis inducing ligand (TRAIL) in human plasmacytoid
      dendritic cells and PBMCs exposed to aldrithiol-2 inactivated HIV or infectious
      influenza virus. Activation-induced TRAIL and expression of cytotoxic T
      lymphocyte antigen 4 (CTLA-4) in isolated CD4+ T cells were also reduced by
      minocycline. Translation of these in vitro findings to in vivo effects, however,
      were mixed as minocycline significantly reduced markers of activation and
      activation-induced cell death (CD25, Fas, caspase-3) but did not affect
      expression of IFNbeta or the IFN-stimulated genes IDO1, FasL, or Mx in the
      spleens of chronically SIV-infected pigtailed macaques. TRAIL expression,
      reflecting the mixed effects of minocycline on activation and type I IFN stimuli,
      was reduced by half, but this change was not significant. These results show that
      minocycline administered after infection may protect against aspects of
      activation-induced cell death during HIV/SIV immune disease, but that in vitro
      effects of minocycline on type I IFN responses are not recapitulated in a rapid
      progressor model in vivo. 

PMID- 24732039
TI  - Combination of liposomal CpG oligodeoxynucleotide 2006 and miltefosine induces
      strong cell-mediated immunity during experimental visceral leishmaniasis.
AB  - Immuno-modulators in combination with antileishmanial drug miltefosine is a
      better therapeutic approach for treatment of Visceral Leishmaniasis (VL) as it
      not only reduces the dose of miltefosine but also shortens the treatment regimen.
      However, immunological mechanisms behind the perceived benefits of this
      combination therapy have not been investigated in detail. In the present study,
      we hypothesized that potential use of drugs that target the host in addition to
      the parasite might represent an alternative strategy for combination therapy. We
      investigated immune responses generated in Leishmania donovani infected animals
      (hamsters and mice) treated with combination of CpG-ODN-2006 and miltefosine at
      short dose regimen. Infected animals were administered CpG-ODN-2006 (0.4 mg/kg,
      single dose), as free and liposomal form, either alone or in combination with
      miltefosine for 5 consecutive days and parasite clearance was evaluated at day 4
      and 7 post treatment. Animals that received liposomal CpG-ODN-2006 (lipo-CpG-ODN
      2006) and sub-curative miltefosine (5 mg/kg) showed the best inhibition of
      parasite multiplication (~97%) which was associated with a biased Th1 immune
      response in. Moreover, compared to all the other treated groups, we observed
      increased mRNA expression levels of pro-inflammatory cytokines (IFN-gamma, TNF
      alpha and IL-12) and significantly suppressed levels of Th2 cytokines (IL-10 and
      TGF-beta) on day 4 post treatment in animals that underwent combination therapy
      with lipo-CpG-ODN-2006 and sub-curative miltefosine. Additionally, same therapy
      also induced heightened iNOS mRNA levels and NO generation, increased IgG2
      antibody level and strong T-cell response in these hamsters compared with all the
      other treated groups. Collectively, our results suggest that combination of lipo
      CpG-ODN-2006 and sub-curative miltefosine generates protective T-cell response in
      an animal model of visceral leishmaniasis which is characterized by strong Th1
      biased immune response thereby underlining our hypothesis that combination
      therapy, at short dose regimen can be used as a novel way of treating visceral
      leishmaniasis. 

PMID- 24732040
TI  - Hypoxia inducible factor-1 alpha as a therapeutic target in multiple myeloma.
AB  - The increasing importance of hypoxia-inducible factor-1alpha (HIF-1alpha) in
      tumorigenesis raises the possibility that agents which specifically inhibit this
      transcription factor, would provide significant therapeutic benefit. The
      constitutive expression of HIF-1alpha in about 35% of Multiple Myeloma (MM)
      patients suggests HIF-1alpha suppression might be part of a therapeutic strategy.
      Accordingly, we explored the effect of EZN-2968, a small 3rd generation antisense
      oligonucleotide against HIF-1alpha, in a panel of MM cell lines and primary
      patients samples. Here, we demonstrated that EZN-2968 is highly specific for HIF
      1alpha mRNA and that exposure of MM cells to EZN-2968 resulted in an efficient
      and homogeneous loading of the cells showing a long lasting low HIF-1alpha
      protein level. In MM cells, HIF-1alpha suppression induced a permanent cell cycle
      arrest by prolonging S-phase through cyclin A modulation and in addition it
      induced a mild apoptotic cell death. Moreover, HIF-1alpha suppression caused a
      metabolic shift that leaded to increased production of ATP by oxidative
      phosphorylation (i.e. Warburg effect reversion), that was confirmed by the
      observed mitochondrial membrane potential decrease. These results show that HIF
      1alpha is an important player in MM homeostasis and that its inhibition by small
      antisense oligonucleotides provides a rationale for novel therapeutic strategy to
      improving MM treatment. 

PMID- 24732041
TI  - A review of atomoxetine effects in young people with developmental disabilities.
AB  - This review summarizes the pharmacokinetic characteristics, pharmacodynamic
      properties, common side effects, and clinical advantages and disadvantages
      associated with atomoxetine (ATX) treatment in typically developing children and
      adults with ADHD. Then the clinical research to date in developmental
      disabilities (DD), including autism spectrum disorders (ASD), is summarized and
      reviewed. Of the 11 relevant reports available, only two were placebo-controlled
      randomized clinical trials, and both focused on a single DD population (ASD). All
      trials but one indicated clinical improvement in ADHD symptoms with ATX, although
      it was difficult to judge the magnitude and validity of reported improvement in
      the absence of placebo controls. Effects of ATX on co-occurring behavioral and
      cognitive symptoms were much less consistent. Appetite decrease, nausea, and
      irritability were the most common adverse events reported among children with DD;
      clinicians should be aware that, as with stimulants, irritability appears to
      occur much more commonly in persons with DD than in typically developing
      individuals. Splitting the dose initially, starting below the recommended
      starting dose, and titrating slowly may prevent or ameliorate side effects.
      Patience is needed for the slow build-up of benefit. CONCLUSIONS: ATX holds
      promise for managing ADHD symptoms in DD, but properly controlled, randomized
      clinical trials of atomoxetine in intellectual disability and ASD are sorely
      needed. Clinicians and researchers should be vigilant for the emergence of
      irritability with ATX treatment. Effects of ATX on cognition in DD are virtually
      unstudied.

PMID- 24732042
TI  - Inactivity, not gluttony, causes obesity.

PMID- 24732045
TI  - Overview on spermatogenesis and sperm structure of Hexapoda.
AB  - The main characteristics of the sperm structure of Hexapoda are reported in the
      review. Data are dealing with the process of spermatogenesis, including the
      aberrant models giving rise to a reduced number of sperm cells. The sperm
      heteromorphism and the giant sperm exceeding the usual sperm size for length and
      width are considered. The characteristics of several components of a typical
      insect sperm are described: the plasma membrane and its glycocalyx, the nucleus,
      the centriole region and the centriole adjunct, the accessory bodies, the
      mitochondrial derivatives and the flagellar axoneme. Finally, a detailed
      description of the main sperm features of each hexapodan group is given with
      emphasis on the flagellar components considered to have great importance in
      phylogenetic considerations. This study may be also useful to those requiring an
      introduction to hexapod reproduction. 

PMID- 24732044
TI  - MiRNA-99a directly regulates AGO2 through translational repression in
      hepatocellular carcinoma.
AB  - The regulation network consisting of microRNAs (miRNAs) and their target genes
      remains largely elusive in hepatocellular carcinoma (HCC), especially the
      reciprocal loop between specific miRNAs and the miRNA processing machinery. In
      this study, we found that miR-99a was remarkably decreased in 111 of 152 (73.03%)
      primary HCC tissues and low-level expression of miR-99a was correlated with low
      tumor differentiation (P=0.001), liver cirrhosis (P=0.015), poor tumor-free
      survival (P=0.004) and overall survival (P=0.006) for HCC patients. By
      restoration of miR-99a, the HCC growth could be considerably inhibited both in
      vitro and in vivo. Subsequently, Argonaute-2 (Ago2), a central component of RNA
      induced silencing complex, was found to be directly regulated by miR-99a via
      translational repression. Overexpression of Ago2 could partly impair the
      inhibitory effect of miR-99a on HCC cells in vitro. Then, we demonstrated that
      Ago2 was upregulated in HCC tissues at both RNA and protein levels and the
      expression of AGO2 protein and miR-99a was negatively correlated within detected
      HCC tissues (r=-0.727, P=0.004). Interestingly, the tumorigenicity of Ago2
      knockdown HCC cells was severely impaired (4/10 vs 10/10, P<0.05), and this was
      in contrast to the miR-99a-overexpressing HCC cells. Functionally, the increased
      AGO2 protein could specifically facilitate oncogenic miR-21 to repress its
      targeted gene phosphatase and tensin homolog (Pten) in HCC, whereas leave the
      regulatory capacity of let-7a on its targeted oncogenes almost unaltered. In
      summary, our study has revealed a novel pathway for the tumor suppressor miR-99a
      to control tumor growth in HCC, via its downstream signaling of AGO2/miR-21/PTEN.
      In addition, this study provides potential strategies for HCC therapy by
      reintroduction of miRNA suppressors. 

PMID- 24732043
TI  - Apocrine secretion in Drosophila salivary glands: subcellular origin, dynamics,
      and identification of secretory proteins.
AB  - In contrast to the well defined mechanism of merocrine exocytosis, the mechanism
      of apocrine secretion, which was first described over 180 years ago, remains
      relatively uncharacterized. We identified apocrine secretory activity in the late
      prepupal salivary glands of Drosophila melanogaster just prior to the execution
      of programmed cell death (PCD). The excellent genetic tools available in
      Drosophila provide an opportunity to dissect for the first time the molecular and
      mechanistic aspects of this process. A prerequisite for such an analysis is to
      have pivotal immunohistochemical, ultrastructural, biochemical and proteomic data
      that fully characterize the process. Here we present data showing that the
      Drosophila salivary glands release all kinds of cellular proteins by an apocrine
      mechanism including cytoskeletal, cytosolic, mitochondrial, nuclear and nucleolar
      components. Surprisingly, the apocrine release of these proteins displays a
      temporal pattern with the sequential release of some proteins (e.g. transcription
      factor BR-C, tumor suppressor p127, cytoskeletal beta-tubulin, non-muscle myosin)
      earlier than others (e.g. filamentous actin, nuclear lamin, mitochondrial
      pyruvate dehydrogenase). Although the apocrine release of proteins takes place
      just prior to the execution of an apoptotic program, the nuclear DNA is never
      released. Western blotting indicates that the secreted proteins remain undegraded
      in the lumen. Following apocrine secretion, the salivary gland cells remain quite
      vital, as they retain highly active transcriptional and protein synthetic
      activity. 

PMID- 24732046
TI  - Tracing and 3-dimensional representation of the primary afferents from the moth
      ear.
AB  - Heliothine moths perceive acoustic information via two auditory sensory neurons
      only. Previous cobalt staining experiments have described the projection pattern
      of the two auditory neurons, called the A1 and the A2 cell, plus one additional
      neuron, the so-called B cell, up to the prothorax. We have obtained new and
      improved data about the projection pattern of the three sensory afferents by
      means of fluorescent staining experiments combined with scanning confocal
      microscopy. The present data show the fine structure of each sensory axon that
      arises from the moth ear and its ascending pathway relative to that of the
      others. In accordance with the previous data, the A2 auditory cell was found to
      extend projections in the pterothorax only. A novel finding is that terminal
      branches of the A2 cell cross the midline. The staining pattern of the two
      remaining neurons, the A1 and B cell, which project tightly together in the
      thoracic ganglia, differ somewhat from that previously described. As demonstrated
      here, one of these two neurons, the A1 cell, terminates in the prothoracic
      ganglion whereas the other, the B cell, projects further on via the cervical
      connectives to the subesophageal ganglion. The current data, therefore, indicate
      that none of the auditory afferents in the heliothine moth projects to the brain.

PMID- 24732048
TI  - Framing Options as Choice or Opportunity: Does the Frame Influence Decisions?
AB  - OBJECTIVE: Health professionals must enable patients to make informed decisions
      about health care choices through unbiased presentation of all options. This
      study examined whether presenting the decision as "opportunity" rather than
      "choice" biased individuals' preferences in the context of trial participation
      for cancer treatment. METHODS: Self-selecting healthy women (N = 124) were
      randomly assigned to the following decision frames: opportunity to take part in
      the trial (opt-in), opportunity to be removed from the trial (opt-out), and
      choice to have standard treatment or take part in the trial (choice). The
      computer-based task required women to make a hypothetical choice about a real
      world cancer treatment trial. The software presented the framed scenario,
      recorded initial preference, presented comprehensive and balanced information,
      traced participants' use of information during decision making, and recorded
      final decision. A posttask paper questionnaire assessed perceived risk,
      attitudes, subjective norm, perceived behavioral control, and satisfaction with
      decision. RESULTS: Framing influenced women's immediate preferences. Opportunity
      frames, whether opt-in or opt-out, introduced a bias as they discouraged women
      from choosing standard treatment. Using the choice frame avoided this bias. The
      opt-out opportunity frame also affected women's perceived social norm; women felt
      that others endorsed the trial option. The framing bias was not present once
      participants had had the opportunity to view detailed information on the options
      within a patient decision aid format. There were no group differences in
      information acquisition and final decisions. Sixteen percent changed their
      initial preference after receiving full information. CONCLUSIONS: A "choice"
      frame, where all treatment options are explicit, is less likely to bias
      preferences. Presentation of full information in parallel, option-by-attribute
      format is likely to "de-bias" the decision frame. Tailoring of information to
      initial preferences would be ill-advised as preferences may change following
      detailed information.

PMID- 24732047
TI  - Size-based enrichment of exfoliated tumor cells in urine increases the
      sensitivity for DNA-based detection of bladder cancer.
AB  - Bladder cancer is diagnosed by cystoscopy, a costly and invasive procedure that
      is associated with patient discomfort. Analysis of tumor-specific markers in DNA
      from sediments of voided urine has the potential for non-invasive detection of
      bladder cancer; however, the sensitivity is limited by low fractions and small
      numbers of tumor cells exfoliated into the urine from low-grade tumors. The
      purpose of this study was to improve the sensitivity for non-invasive detection
      of bladder cancer by size-based capture and enrichment of tumor cells in urine.
      In a split-sample set-up, urine from a consecutive series of patients with
      primary or recurrent bladder tumors (N = 189) was processed by microfiltration
      using a membrane filter with a defined pore-size, and sedimentation by
      centrifugation, respectively. DNA from the samples was analyzed for seven bladder
      tumor-associated methylation markers using MethyLight and pyrosequencing assays.
      The fraction of tumor-derived DNA was higher in the filter samples than in the
      corresponding sediments for all markers (p<0.000001). Across all tumor stages,
      the number of cases positive for one or more markers was 87% in filter samples
      compared to 80% in the corresponding sediments. The largest increase in
      sensitivity was achieved in low-grade Ta tumors, with 82 out of 98 cases positive
      in the filter samples (84%) versus 74 out of 98 in the sediments (75%). Our
      results show that pre-analytic processing of voided urine by size-based
      filtration can increase the sensitivity for DNA-based detection of bladder
      cancer. 

PMID- 24732049
TI  - Confusing Relative Risk with Absolute Risk Is Associated with More Enthusiastic
      Beliefs about the Value of Cancer Screening.
AB  - BACKGROUND: Reviews of how data are presented in medical literature document that
      the benefit from an intervention is often exaggerated relative to the harm (e.g.,
      relative risk for benefit and absolute risk for harm). Such mismatched
      presentations may create unwarranted enthusiasm, especially among those who
      misinterpret the statistics presented. The objective was to determine whether
      misinterpretation of risk data predicts enthusiasm for cancer screening. METHODS:
      The authors administered a survey with 14 items assessing beliefs about cancer
      screening and 6 items measuring data interpretation ability. Multiple linear
      regression was used to evaluate the association between data interpretation and
      enthusiasm for cancer screening, with adjustment for gender and year graduated
      from medical school. RESULTS: Eighty-eight of 139 physicians at a state-wide
      professional meeting returned completed surveys (63% response rate). Lower data
      interpretation scores were associated with higher enthusiasm for cancer screening
      scores (P = 0.004) in the adjusted primary analysis. Confusing relative risk with
      absolute risk appeared to drive the overall association. CONCLUSIONS: Biased
      presentations of risk data could affect general beliefs about the value of cancer
      screening, especially among physicians who uncritically accept mismatched
      presentations of data.

PMID- 24732050
TI  - Unveiling the complex organization of recurrent patterns in spiking dynamical
      systems.
AB  - Complex systems displaying recurrent spike patterns are ubiquitous in nature.
      Understanding the organization of these patterns is a challenging task. Here we
      study experimentally the spiking output of a semiconductor laser with feedback.
      By using symbolic analysis we unveil a nontrivial organization of patterns,
      revealing serial spike correlations. The probabilities of the patterns display a
      well-defined, hierarchical and clustered structure that can be understood in
      terms of a delayed model. Most importantly, we identify a minimal model, a
      modified circle map, which displays the same symbolic organization. The validity
      of this minimal model is confirmed by analyzing the output of the forced laser.
      Since the circle map describes many dynamical systems, including neurons and
      cardiac cells, our results suggest that similar correlations and hierarchies of
      patterns can be found in other systems. Our findings also pave the way for
      optical neurons that could provide a controllable set up to mimic neuronal
      activity. 

PMID- 24732051
TI  - Rat induced pluripotent stem cells protect H9C2 cells from cellular senescence
      via a paracrine mechanism.
AB  - OBJECTIVES: Cellular senescence may play an important role in the pathology of
      heart aging. We aimed to explore whether induced pluripotent stem cells (iPSCs)
      could inhibit cardiac cellular senescence via a paracrine mechanism. METHODS: We
      collected iPSC culture supernatant, with or without oxidative stress, as
      conditioned medium (CM) for the rat cardiomyocyte-derived cell line H9C2. Then we
      treated H9C2 cells, cultured with or without CM, with hypoxia/reoxygenation to
      induce cellular senescence and measured senescence-associated beta-galactosidase
      (SA-beta-gal) activity, G1 cell proportion and expression of the cell cycle
      regulators p16(INK4a), p21(Waf1/Cip1) and p53 at mRNA and protein levels in H9C2
      cells. In addition, we used Luminex-based analysis to measure concentrations of
      trophic factors in iPSC-derived CM. RESULTS: We found that iPSC-derived CM
      reduced SA-beta-gal activity, attenuated G1 cell cycle arrest and reduced the
      expression of p16(INK4a), p21(Waf1/Cip1) and p53 in H9C2 cells. Furthermore, the
      CM contained more trophic factors, e.g. tissue inhibitor of metalloproteinase-1
      and vascular endothelial growth factor, than H9C2-derived CM. CONCLUSIONS:
      Paracrine factors released from iPSCs prevent stress-induced senescence of H9C2
      cells by inhibiting p53-p21 and p16-pRb pathways. This is the first report
      demonstrating that antisenescence effects of stem cell therapy may be a novel
      therapeutic strategy for age-related cardiovascular disease.

PMID- 24732052
TI  - Detecting prompt gamma emission during proton therapy: the effects of detector
      size and distance from the patient.
AB  - Recent studies have suggested that the characteristics of prompt gammas (PGs)
      emitted from excited nuclei during proton therapy are advantageous for
      determining beam range during treatment delivery. Since PGs are only emitted
      while the beam is on, the feasibility of using PGs for online treatment
      verification depends greatly on the design of highly efficient detectors. The
      purpose of this work is to characterize how PG detection changes as a function of
      distance from the patient as a means of guiding the design and usage of clinical
      PG imaging detectors. Using a Monte Carlo model (GEANT4.9.4) we studied the
      detection rate (PGs per incident proton) of a high purity germanium detector for
      both the total PG emission and the characteristic 6.13 MeV PG emission from (16)O
      emitted during proton irradiation. The PG detection rate was calculated as a
      function of distance from the isocenter of the proton treatment nozzle for: (1) a
      water phantom irradiated with a proton pencil beam and (2) a prostate patient
      irradiated with a scanning beam proton therapy treatment field (lateral field
      size: ~6 cm * 6 cm, beam range: 23.5 cm). An analytical expression of the PG
      detection rate as a function of distance from isocenter, detector size, and
      proton beam energy was then developed. The detection rates were found to be 1.3 *
      10(-6) for oxygen and 3.9 * 10(-4) for the total PG emission, respectively, with
      the detector placed 11 cm from isocenter for a 40 MeV pencil beam irradiating a
      water phantom. The total PG detection rate increased by ~85 +/- 3% for beam
      energies greater than 150 MeV. The detection rate was found to be approximately
      2.1 * 10(-6) and 1.7 * 10(-3) for oxygen and total PG emission, respectively,
      during delivery of a single pencil beam during a scanning beam treatment for
      prostate cancer. The PG detection rate as a function of distance from isocenter
      during irradiation of a water phantom with a single proton pencil beam was
      described well by the model of a point source irradiating a cylindrical detector
      of a known diameter over the range of beam energies commonly used for proton
      therapy. For the patient studies, it was necessary to divide the point source
      equation by an exponential factor in order to correctly predict the falloff of
      the PG detection rate as a function of distance from isocenter. 

PMID- 24732053
TI  - Fish intake and ovarian cancer risk: a meta-analysis of 15 case-control and
      cohort studies.
AB  - BACKGROUND: Previous epidemiological studies have shown that fish consumption may
      modify the risk of ovarian cancer. However, these studies yielded controversial
      results. The present meta-analysis was undertaken to evaluate the relationship
      between fish intake and ovarian cancer risk. METHODS: A literature search was
      carried out using Pubmed, Embase, and Cochrane Library Central database for all
      relevant studies up to August 2013. We pooled the relative risks (RR) from
      individual studies using fixed-effect or random-effect model, and carried out
      heterogeneity and publication bias analyses. RESULTS: A total of 15 (ten case
      control, and five cohort) studies were included in the present meta-analysis,
      representing data for 889,033 female subjects and 6,087 ovarian cancer cases. We
      found that total fish intake was not significantly associated with the risk of
      ovarian cancer among cohort studies (RR = 1.04 95% CI [0.89, 1.22]) as well as
      case-control studies (RR = 0.90, 95% CI [0.73,1.12]). There was no evidence of
      publication bias as suggested by Begg's test (P = 0.55) and Egger's test(P =
      0.29). CONCLUSIONS: The present meta-analysis showed that total fish consumption
      was not significantly associated with the risk of ovarian cancer. Further
      analysis on different fish species and food preparation methods should be
      conducted in future studies.

PMID- 24732054
TI  - The 'dark side' of chronic obstructive pulmonary disease.

PMID- 24732055
TI  - Evaluation of renal function under controlled hypotension in zero ischemia
      robotic assisted partial nephrectomy.
AB  - BACKGROUND/AIMS: In partial nephrectomy with hilar clamping every minute of
      ischemia can impair renal function, thus great importance is having the
      controlled hypotension as a part of zero ischemia technique. The aim of the study
      is to evaluate the effects of hypotensive anesthesia on renal function, in
      patients undergoing robotic assisted partial nephrectomy (RAPN) , during surgery
      and at 3 months follow up. METHODS: This is a prospective study of 100 patients,
      ASA 1-2, who underwent zero ischemia RAPN under controlled hypotension (CH) from
      December 2011 through to May 2013. Serum creatinine, BUN, estimated glomerular
      filtration rates (eGFR), fractional excretion of sodium (FSE) and technetium Tc
      99m mercaptoacetyltriglycine (99mTC-MAG-3), renal scintigraphy with effective
      renal plasma flow (ERPF) were evaluated. RESULTS: Mean duration of CH was 50 +/-
      4 minutes. Acute renal failure wasn't observed in any of the patients. A
      significant variation of eGFR during the procedure and 24 hours after surgery was
      observed. No significant variation of BUN and FSE was detected. Comparing
      preoperative ERPF of the operated kidney with ERPF 3 months after surgery, it
      decreased by 2%. CONCLUSION: In patients with normal preoperative renal function
      CH didn't show any detrimental impact on renal function during and after robotic
      assisted partial nephrectomy.

PMID- 24732057
TI  - Topical amphotericin B in combination with standard therapy for severe
      necrotizing skin and soft-tissue mucormycosis in an infant with bilineal
      leukemia: case report and review.
AB  - During chemotherapy for bilineal leukemia, a 6-month-old infant presented with a
      necrotizing skin and soft-tissue infection of the chest wall due to Rhizopus sp.
      Successful outcome was achieved by systemically administered liposomal
      amphotericin B and local wound control with the novel administration of topical
      deoxycholate amphotericin B and surgical resection. 

PMID- 24732058
TI  - Inadvertent high-dose therapy with temozolomide in a child with recurrent pontine
      glioma followed by a rapid clinical response but deteriorated after substitution
      with low-dose therapy.
AB  - We present a case of inadvertent high-dose therapy with temozolomide in a child
      with recurrent diffuse intrinsic pontine glioma followed by a rapid clinical
      response. The patient was a 7-year-old boy who initially presented with a history
      of left facial palsy, double vision, headache, and ataxia. His symptoms were
      completely resolved following radiotherapy but recurred 3 months after. Following
      recurrence, he received temozolomide in a dose >3 times higher than prescribed
      inadvertently but tolerated well with a rapid clinical response. He eventually
      deteriorated after he was substituted with a lower dose of temozolomide and died.

PMID- 24732059
TI  - Anterior segment invasion in retinoblastoma: is it a risk factor for extraocular
      relapse?
AB  - We report a retrospective review of patients with retinoblastoma and anterior
      segment invasion (ASI) as risk factors for extraocular relapse. Only those with
      ASI combined with postlaminar optic nerve invasion and/or scleral invasion
      received adjuvant chemotherapy and those with tumor at the resection margin
      received orbital radiotherapy. Those with only uveal invasion did not receive
      adjuvant therapy. Of 479 evaluable patients, 67 patients had pathologically
      confirmed ASI, including 52 with anterior chamber invasion and 47 with iris or
      ciliary body invasion. ASI occurred with other pathology risk factors (25 had
      concomitant posterior uveal invasion, 36 had postlaminar optic nerve invasion, 11
      with cut-end invasion, and 25 with scleral invasion). The 5-year disease-free
      survival (pDFS) was 0.9 (95% CI, 0.8-0.95) for children with ASI with no
      significant differences among children with other pathology risk factors with and
      without ASI. ASI was not significantly associated with extraocular relapse in
      multivariate analysis. There were no significant differences in pDFS for patients
      with anterior chamber invasion and those with iris-ciliary body invasion (pDFS
      0.89 [95% CI, 0.65-0.96] vs. 0.93 [95% CI, 0.61-0.98]). To conclude, ASI was seen
      with other pathology risk factors and it did not add a significant risk for
      extraocular relapse. 

PMID- 24732060
TI  - Public awareness regarding children vaccination in Jordan.
AB  - Immunization can contribute to a dramatic reduction in number of vaccine
      preventable diseases among children. The aim of this study is to investigate
      mothers' awareness about child vaccines and vaccination in Jordan. This study was
      a community-based, cross-sectional study that was performed at public places in
      Irbid City. Data was collected from 506 mothers. After verbal approval, mothers
      were interviewed to assess their knowledge, attitudes, and practice toward
      vaccination. Results show that majority of mothers had acceptable knowledge and
      positive attitude toward vaccination. Most of mothers (94.7-86.8%) were able to
      identify vaccines that are mandatory as per the national vaccination program.
      Lower knowledge was observed among mothers (71.6%) for HIB vaccination being
      mandatory. Most mothers (97.2%) had vaccination card for their baby form the
      national vaccination programs. Vaccination delay was reported by about 36.6% of
      mothers and was shown to be associated with significantly (P = 0.001) lower
      vaccination knowledge/attitude score. Additionally, mothers who reported to be
      regularly offered information about vaccination during visits and those who
      identified medical staff members as their major information source had
      significantly higher vaccination knowledge/attitude score (P = 0.002). In
      conclusion, vaccination coverage rate is high; however, some aspects of
      knowledge, attitudes, and practice of vaccination need to be improved. Knowledge
      and attitudes of mothers were directly associated with their practice of
      vaccination. Medical staff education about vaccination during each visit seems to
      be the most effective tool that directly reflects on better practice of
      vaccination such as reducing the possibility for vaccination delay. 

PMID- 24732061
TI  - Expression and correlation analysis of IL-4, IFN-gamma and FcalphaRI in tonsillar
      mononuclear cells in patients with IgA nephropathy.
AB  - BACKGROUND: Clinical deterioration of IgA nephropathy (IgAN) is frequently
      preceded by episodes of upper respiratory tract infection such as tonsillitis.
      The aim of this study was attempt to investigate the expression and correlation
      of IL-4, IFN-gamma and FcalphaRI in tonsillar mononuclear cells under
      stimulations of alpha-hemolytic streptococcus (HS) or lipopolysaccharide (LPS) in
      patients with IgA nephropathy. METHODS: Tonsillar mononuclear cells isolated from
      26 patients with IgAN and 25 patients with chronic tonsillitis (CT) as controls
      were cultured for 72h with or without alpha-hemolytic streptococcus (HS) and
      lipopolysaccharide (LPS) stimulation. Concentration of IL-4 and IFN-gamma level
      were determined by ELISA. Expression levels of IL-4, IFN-gamma and FcalphaRI mRNA
      were measured by real-time PCR, respectively. FcalphaRI expressing cells were
      tracked by flow cytometry. RESULTS: The supernatant concentration of IL-4, IFN
      gamma and the expression of IL-4, IFN-gamma and FcalphaRI mRNA in the IgA
      nephropathy group was markedly increased compared with the non-IgAN group. With
      the stimulation of HS, the production of IL-4 and the FcalphaRI expressing cells
      in the IgA nephropathy group was significantly increased than the non-IgAN group,
      while the secretion of IFN-gamma was remarkably decreased in the IgA nephropathy
      group than the non-IgAN group. Upon the LPS stimulation, the concentration of IL
      4, IFN-gamma in the supernatant of the IgA nephropathy group was markedly
      increased compared with the non-IgAN group. However, there wasn't significant
      difference in the FcalphaRI expressing cells between the LPS stimulated IgAN
      group and the non-IgAN group. The expression of FcalphaRI is in a negative
      correlation with IL-4 while positive with IFN-gamma. CONCLUSION: The tonsillar
      mononuclear cells of IgAN may in a state of overactive immune response, which
      probably can promote the secretion of Th cytokines, involving in the pathogenesis
      of IgAN.

PMID- 24732062
TI  - Evaluation of Leishmania donovani disulfide isomerase as a potential target of
      cellular immunity against visceral leishmaniasis.
AB  - In Leishmania species, protein disulfide isomerase (PDI) - a redox chaperone is
      primarily associated with virulence and survival. The precise mechanism,
      especially in relation to redox changes and its effects on immunological
      responses in visceral leishmaniasis (VL) is not completely understood as yet.
      Therefore, we purified a recombinant PDI from Leishmania donovani (r-LdPDI) which
      was of ~15 kDa molecular size and examined its effects on immunological responses
      in peripheral blood (PBMC) of human VL cases. For these studies, alanine was
      tested as an inhibitor and was used in parallel to all experiments. This protein
      was identified to have a direct correlation with parasite growth which
      significantly increased number of promastigotes as well as axenic amastigotes
      after 96 h of culture. Our experiments examining the immunological response
      against r-LdPDI also indicate the activation of pro-L. donovani dictated
      immunological responses in VL. The stimulation of PBMC with r-LdPDI induced
      lactate dehydrogenase (LDH) activities and up regulated interleukin-10 (IL-10)
      production but not the HLA-DR expression, Nitric oxide (NO) release and IFN-gamma
      production indicating a pivoted role for r-LdPDI in causing a strong
      immunosuppression in a susceptible host. Further, we observed that an addition of
      alanine in L. donovani culture offers a significant inhibition in growth of
      parasite and helps in reconstitution of protective immune response in VL cases.
      Therefore, we demonstrate a future cross talk on use of alanine which can reduce
      the activities of PDI of L. donovani, eliminating the parasite induced
      immunosuppression and inducing collateral host protective response in VL.

PMID- 24732063
TI  - Differential thermal stability of human, bovine and ovine Follicle-Stimulating
      Hormone (FSH) and Luteinizing Hormone (LH) quaternary structures.
AB  - Quaternary structure of human, bovine and ovine Follicle-Stimulating Hormones
      (hFSH, bFSH and oFSH) and Luteinizing Hormone was assessed in sandwich ELISAs
      using monoclonal anti-oFSHbeta or anti-oLHbeta antibodies, respectively, for
      capture and a biotinylated anti-hFSHalpha (alpha4 epitope) for detection. Neither
      free subunit gave any signal in this assay so that it was possible to measure the
      residual heterodimeric fraction after thermal treatment of the gonadotropins
      under study. The hormones were subjected to 5-min heating between 37 and 90 
      degrees C before rapid cooling in melting ice before ELISA. The data show half
      dissociation of natural and recombinant human and ovine FSH preparations between
      68 and 74  degrees C whereas bovine FSH preparations exhibited lower stability in
      these conditions with half-dissociation between 61 and 64  degrees C. Moreover,
      whereas all human and bovine as well as most ovine FSH preparations were fully
      dissociated at temperatures above 80  degrees C, one natural oFSH and one
      recombinant hLH preparations contained an important fraction that resisted
      dissociation even at 93  degrees C and retained in vitro bioactivity. This
      suggests the existence of gonadotropin alphabeta heterodimer with covalently
      linked subunits. Similarly, about 20% of the recombinant hLH preparation was also
      found withstand heat denaturation and also probably to have cross-linked
      subunits. The origin and chemical nature of these inter-subunit bonds remain to
      be determined.

PMID- 24732064
TI  - Phagocytic activity of LPS tolerant macrophages.
AB  - Endotoxin tolerance is defined as a reduced capacity of the host to respond to
      LPS activation following a first exposure to this stimulus. It affects all
      leukocytes and regarding macrophages, most studies focus on the reduced ability
      of these cells to secrete pro-inflammatory cytokines. Therefore, we evaluated
      other macrophages functions (fungicidal capacity, reactive oxygen species
      production and antigen presentation) in cells from tolerant mice. We have
      performed a tolerance model in our laboratory that does not stimulate directly
      the place from where the cells will be removed (peritoneal cavity). Mouse
      received subcutaneous injections of LPS in the scruff for 5 days and we analyze
      the capacity of peritoneal macrophages to phagocyte using three different
      receptors: Fc, C3b and mannose receptors. We found a reduction in the
      phagocytosis of erythrocytes and Candida albicans related to the Fc and mannose
      receptors. These differences can be due to a macrophage reprogramming, as
      demonstrated by altered expression of cytokines and chemokines. Despite this
      reduction in phagocytosis capacity, macrophages from tolerant animals exhibited
      enhanced hydrogen peroxide production and expression of antigen presentation
      molecules, suggesting that their ability to combat an infection is improved. In
      summary, our data indicates that LPS tolerance drives macrophages from a
      predominant release of proinflammatory mediators that amplify inflammation and
      host damage toward a better killing and antigen presentation state.

PMID- 24732065
TI  - Tenocyte activation and regulation of complement factors in response to in vitro
      cell injury.
AB  - Inferior tendon healing can lead to scarring and tendinopathy. The role of
      complement in tendon healing is still unclear. The aim of this study was to
      understand tenocytes response to mechanical injury and whether complement is
      regulated by injury. Tenocytes were injured using an optimized automated scratch
      assay model. Using a self-assembled plotter system, 50 parallel lines of injury
      were created in a 6 cm diameter tenocyte cell layer. Tenocytes mitotic activity
      and survival post injury was assessed using FDA/ethidiumbromide assay.
      Furthermore, this injury model was combined with stimulation of the tenocytes
      with the complement split fragment C3a. Gene expression of C3aR, C5aR (CD88),
      CD46, CD55, tumor necrosis factor (TNF)alpha, interleukin (IL)-1beta, matrix
      metalloproteinase (MMP)-1 was analyzed. Immunolabeling for C5aR and CD55 was
      performed. An enhanced mitotic activity and some dead cells were detected in the
      vicinity of the scratches. Gene expression of the C3aR was suppressed after 4 h
      but induced after 24 h post injury. C5aR was down-regulated at 24 h, CD46 and
      CD55 were induced at 24 h in response to injury and CD55 was also elevated at 4
      h. MMP-1 was upregulated by injury but both proinflammatory cytokines remained
      mainly unaffected. Combination of injury with C3a stimulation led to an enhanced
      C3aR, CD55 and TNFalpha gene expression. According to the gene expression data,
      the protein expression of C5aR was reduced and that of CD55 induced. In summary,
      a specific response of complement regulation was found in mechanically injured
      tenocytes which may be involved in healing responses.

PMID- 24732066
TI  - Development of a novel cross-streaking method for isolation, confirmation, and
      enumeration of Salmonella from irrigation ponds.
AB  - The 2013 Produce Safety Rules in Food Safety Modernization Act (FSMA) require
      regular testing for generic Escherichia coli in agricultural water intended for
      pre-harvest contact with the edible portion of fresh produce. However, the use of
      fecal contamination indicators frequently does not correctly reflect distribution
      of foodborne pathogens such as Salmonella enterica, and ensuring food safety may
      require direct detection and enumeration of pathogens in agricultural settings.
      Herein we report the evaluation of different cost-effective methods for
      quantification, isolation, and confirmation of Salmonella in irrigation pond
      water and sediment samples. A most probably number (MPN) dual enrichment culture
      method was used in combination with differential and selective agars, XLT4 and
      CHROMagarTM Salmonella plus (CSP). The necessity for PCR confirmation was
      evaluated, and methods were compared by cost and performance measures (i.e.,
      sensitivity, specificity, positive predictive value, and negative predictive
      value). Statistical analyses showed that using XLT4 as the initial selective agar
      to isolate Salmonella colonies improved recovery compared to CSP agar; however,
      PCR confirmation was required to avoid false positive results on either agar.
      Therefore, a novel cross-streaking method utilizing CHROMagarTM agar for
      individual colony confirmation of Salmonella presence/absence on XLT4 was
      developed. This method classifies the colony as positive if typical Salmonella
      appearance is observed on both agars. Statistical analysis showed that this
      method was as effective as PCR for species confirmation of pure individual
      strains isolated from enrichment cultures (sensitivity=0.99, specificity=1.00,
      relative to PCR). This method offers a cost-effective alternative to PCR that
      would increase the capacity and sensitivity of Salmonella evaluation. 

PMID- 24732067
TI  - Innovating aging: promises and pitfalls on the road to life extension.
AB  - One of the main benefits of the dramatic technological progress over the last two
      centuries is the enormous increase in human life expectancy, which has now
      reached record highs. After conquering most childhood diseases and a fair
      fraction of the diseases that plague adulthood, medical technology is now mainly
      preoccupied by age-related disorders. Further progress is dependent on
      circumventing the traditional medical focus on individual diseases and instead
      targeting aging as a whole as the ultimate cause of the health problems that
      affect humankind at old age. In principle, a major effort to control the gradual
      accumulation of molecular and cellular damage - considered by many as the
      ultimate cause of intrinsic aging - may rapidly lead to interventions for
      regenerating aged and worn-out tissues and organs. While considered impossible by
      many, there really is no reason to reject this as scientifically implausible.
      However, as we posit, it is not only scientific progress that is currently a
      limiting factor, but societal factors that hinder and may ultimately prevent
      further progress in testing and adopting the many possible interventions to cure
      aging.

PMID- 24732068
TI  - Analytical challenges and regulatory requirements for nasal drug products in
      europe and the u.s.
AB  - Nasal drug delivery can be assessed by a variety of means and regulatory
      agencies, e.g., the Food and Drug Administration (FDA) and the European Medicines
      Agency (EMA) have published a set of guidelines and regulations proposing in
      vitro test methods for the characterization of nasal drug products. This article
      gives a summary of the FDA and EMA requirements regarding the determination of
      droplet size distribution (DSD), plume geometry, spray pattern and shot weights
      of solution nasal sprays and discusses the analytical challenges that can occur
      when performing these measurements. In order to support findings from the
      literature, studies were performed using a standard nasal spray pump and aqueous
      model formulations. The aim was to identify possible method-, device- and
      formulation-dependent influencing factors. The literature review, as well as the
      results from the studies show that DSD, plume geometry and spray pattern are
      influenced by, e.g., the viscosity of the solution, the design of the device and
      the actuation parameters, particularly the stroke length, actuation velocity and
      actuation force. The dominant factor influencing shot weights, however, is the
      adjustment of the actuation parameters, especially stroke length and actuation
      velocity. Consequently, for routine measurements assuring, e.g., the quality of a
      solution nasal spray or, for in vitro bioequivalence studies, the critical
      parameters, have to be identified and considered in method development in order
      to obtain reproducible and reliable results. 

PMID- 24732070
TI  - Selective attention reduces physiological noise in the external ear canals of
      humans. II: visual attention.
AB  - Human subjects performed in several behavioral conditions requiring, or not
      requiring, selective attention to visual stimuli. Specifically, the attentional
      task was to recognize strings of digits that had been presented visually. A
      nonlinear version of the stimulus-frequency otoacoustic emission (SFOAE), called
      the nSFOAE, was collected during the visual presentation of the digits. The
      segment of the physiological response discussed here occurred during brief silent
      periods immediately following the SFOAE-evoking stimuli. For all subjects tested,
      the physiological-noise magnitudes were substantially weaker (less noisy) during
      the tasks requiring the most visual attention. Effect sizes for the differences
      were >2.0. Our interpretation is that cortico-olivo influences adjusted the
      magnitude of efferent activation during the SFOAE-evoking stimulation depending
      upon the attention task in effect, and then that magnitude of efferent activation
      persisted throughout the silent period where it also modulated the physiological
      noise present. Because the results were highly similar to those obtained when the
      behavioral conditions involved auditory attention, similar mechanisms appear to
      operate both across modalities and within modalities. Supplementary measurements
      revealed that the efferent activation was spectrally global, as it was for
      auditory attention.

PMID- 24732069
TI  - Selective attention reduces physiological noise in the external ear canals of
      humans. I: auditory attention.
AB  - In this study, a nonlinear version of the stimulus-frequency OAE (SFOAE), called
      the nSFOAE, was used to measure cochlear responses from human subjects while they
      simultaneously performed behavioral tasks requiring, or not requiring, selective
      auditory attention. Appended to each stimulus presentation, and included in the
      calculation of each nSFOAE response, was a 30-ms silent period that was used to
      estimate the level of the inherent physiological noise in the ear canals of our
      subjects during each behavioral condition. Physiological-noise magnitudes were
      higher (noisier) for all subjects in the inattention task, and lower (quieter) in
      the selective auditory-attention tasks. These noise measures initially were made
      at the frequency of our nSFOAE probe tone (4.0 kHz), but the same attention
      effects also were observed across a wide range of frequencies. We attribute the
      observed differences in physiological-noise magnitudes between the inattention
      and attention conditions to different levels of efferent activation associated
      with the differing attentional demands of the behavioral tasks. One hypothesis is
      that when the attentional demand is relatively great, efferent activation is
      relatively high, and a decrease in the gain of the cochlear amplifier leads to
      lower-amplitude cochlear activity, and thus a smaller measure of noise from the
      ear.

PMID- 24732071
TI  - Beta2-adrenergic agonist use and the risk of multiple sclerosis: a total
      population-based case-control study.
AB  - OBJECTIVE: The aim of this study was to investigate whether the use of fenoterol,
      a beta2-adrenergic agonist, was associated with multiple sclerosis (MS) risk by
      conducting a total population-based case-control study in Taiwan. METHODS: A
      total of 578 patients with newly diagnosed MS who had a severely disabling
      disease (SDD) certificate between January 1, 2002 and December 1, 2008 comprised
      the case group. These cases were compared with 2890 gender-, age-, residence-,
      and insurance premium-matched controls. Fenoterol use was analyzed using a
      conditional logistic regression model that controlled for asthma, chronic
      obstructive pulmonary disease (COPD), salbutamol and steroid use. RESULTS:
      Compared with the group of people who did not use fenoterol, the adjusted odds
      ratios were 0.67 (95% confidence interval (CI) = 0.48-0.93, p = 0.016) for the
      group prescribed fenoterol below 2.25 cumulative defined daily dose (cDDD) and
      0.49 (95% CI = 0.33-0.71, p < 0.001) for the group with a cumulative fenoterol
      use of more than 2.25 cDDD. The dose-response relationship was similar within the
      non-asthma patients. The associations were similar between males and females, but
      differences between age groups were observed. CONCLUSIONS: The results of this
      study suggest that fenoterol use may reduce the risk of MS.

PMID- 24732072
TI  - An agent-based model of the response to angioplasty and bare-metal stent
      deployment in an atherosclerotic blood vessel.
AB  - PURPOSE: While animal models are widely used to investigate the development of
      restenosis in blood vessels following an intervention, computational models offer
      another means for investigating this phenomenon. A computational model of the
      response of a treated vessel would allow investigators to assess the effects of
      altering certain vessel- and stent-related variables. The authors aimed to
      develop a novel computational model of restenosis development following an
      angioplasty and bare-metal stent implantation in an atherosclerotic vessel using
      agent-based modeling techniques. The presented model is intended to demonstrate
      the body's response to the intervention and to explore how different vessel
      geometries or stent arrangements may affect restenosis development. METHODS: The
      model was created on a two-dimensional grid space. It utilizes the post
      procedural vessel lumen diameter and stent information as its input parameters.
      The simulation starting point of the model is an atherosclerotic vessel after an
      angioplasty and stent implantation procedure. The model subsequently generates
      the final lumen diameter, percent change in lumen cross-sectional area, time to
      lumen diameter stabilization, and local concentrations of inflammatory cytokines
      upon simulation completion. Simulation results were directly compared with the
      results from serial imaging studies and cytokine levels studies in
      atherosclerotic patients from the relevant literature. RESULTS: The final lumen
      diameter results were all within one standard deviation of the mean lumen
      diameters reported in the comparison studies. The overlapping-stent simulations
      yielded results that matched published trends. The cytokine levels remained
      within the range of physiological levels throughout the simulations. CONCLUSION:
      We developed a novel computational model that successfully simulated the
      development of restenosis in a blood vessel following an angioplasty and bare
      metal stent deployment based on the characteristics of the vessel cross-section
      and stent. A further development of this model could ultimately be used as a
      predictive tool to depict patient outcomes and inform treatment options.

PMID- 24732073
TI  - Preliminary evaluation of the dosimetric accuracy of the in vivo plastic
      scintillation detector OARtrac system for prostate cancer treatments.
AB  - A promising, new, in vivo prostate dosimetry system has been developed for
      clinical radiation therapy. This work outlines the preliminary end-to-end testing
      of the accuracy and precision of the new OARtrac scintillation dosimetry system.
      We tested 94 calibrated plastic scintillation detector (PSD) probes before their
      final integration into endorectal balloon assemblies. These probes had been
      calibrated at The University of Texas MD Anderson Cancer Center Dosimetry
      Laboratory. We used a complete clinical OARtrac system including the PSD probes,
      charge coupled device camera monitoring system, and the manufacturer's integrated
      software package. The PSD probes were irradiated at 6 MV in a Solid Water(r)
      phantom. Irradiations were performed with a 6 MV linear accelerator using
      anterior-posterior/posterior-anterior matched fields to a maximum dose of 200 cGy
      in a 100 cm source-axis distance geometry. As a whole, the OARtrac system has
      good accuracy with a mean error of 0.01% and an error spread of +/-5.4% at the
      95% confidence interval. These results reflect the PSD probes' accuracy before
      their final insertion into endorectal balloons. Future work will test the
      dosimetric effects of mounting the PSD probes within the endorectal balloon
      assemblies. 

PMID- 24732075
TI  - Tracing innate immune defences along the path of Listeria monocytogenes
      infection.
AB  - The pathogenic gram-positive bacteria, Listeria monocytogenes is a facultative
      infectious intracellular pathogen that causes listeriosis. Effective elimination
      of infection is dependent upon a functioning innate immune system and activation
      of inflammatory responses by pathogen recognition receptors (PRRs). In this
      review, we trace the route of L. monocytogenes invasion as it disseminates from
      the intestinal epithelium, through the bloodstream of the host, to the liver and
      spleen. Along this route, we highlight the diverse, region specific, innate
      defences in place throughout the course of infection. We provide an overview of
      recent advances in our knowledge of key innate immune defences against L.
      monocytogenes, focusing on the PRRs in various cell types known to be critical in
      the detection of this pathogen. 

PMID- 24732074
TI  - The effect of polyamines on the binding of anti-DNA antibodies from patients with
      SLE and normal human subjects.
AB  - Antibodies to DNA (anti-DNA) are the serological hallmark of systemic lupus
      erythematosus (SLE). To elucidate specificity further, the effect of polyamines
      on the binding of anti-DNA antibodies from patients with lupus was tested by
      ELISA to calf thymus (CT) DNA; we also assessed the binding of plasmas of
      patients and normal human subjects (NHS) to Micrococcus luteus (MC) DNA. As these
      studies showed, spermine can dose-dependently inhibit SLE anti-DNA binding to CT
      DNA and can promote dissociation of preformed immune complexes. With MC DNA as
      antigen, spermine failed to inhibit the NHS anti-DNA binding. Studies using
      plasmas adsorbed to a CT DNA cellulose affinity indicated that SLE plasmas are
      mixtures of anti-DNA that differ in inhibition by spermine and binding to
      conserved and non-conserved determinants. Together, these studies demonstrate
      that spermine can influence the binding of anti-DNA autoantibodies and may
      contribute to the antigenicity of DNA. 

PMID- 24732076
TI  - OX40 engagement depletes intratumoral Tregs via activating FcgammaRs, leading to
      antitumor efficacy.
AB  - Antibodies targeting checkpoint inhibitors or co-stimulatory receptors on T cells
      have shown significant antitumor efficacy in preclinical and clinical studies. In
      mouse tumor models, engagement of activating Fcgamma receptor (FcgammaR)
      expressing immune cells was recently shown to be required for the tumoricidal
      activity of antibodies recognizing the tumor necrosis factor superfamily receptor
      (TNFR) GITR (CD357) and CTLA-4 (CD152). In particular, activating FcgammaRs
      facilitated the selective elimination of intratumoral T-cell populations.
      However, it remains unclear whether FcgammaRs contribute to the antitumor
      efficacy of other immunomodulatory antibodies. Here, we explored the mechanism of
      antitumor activity mediated by an agonistic antibody (clone OX86) to the co
      stimulatory TNFR OX40 (CD134). OX40 was highly expressed by intratumoral T cells,
      particularly those of the FoxP3(+) regulatory T-cell (Treg) lineage. OX86
      administration resulted in the depletion of intratumoral regulatory T cells in an
      activating FcgammaR-dependent manner, which correlated with tumor regression.
      Together with previous data from our group and others, these findings support a
      mechanism whereby antibodies targeting antigens highly expressed by intratumoral
      T cells can mediate their elimination by FcgammaR-expressing immune cells, and
      facilitate subsequent antitumor immunity.

PMID- 24732077
TI  - Cross-leg flaps and reconstructive surgery in the 21st century.

PMID- 24732078
TI  - Lipotransfer: the potential from bench to bedside.
AB  - The development of autologous fat grafting to augment or reconstruct tissue
      defects has become an increasingly popular modality among plastic surgeons.
      Despite its popularity, a standardized fat grafting protocol has yet to be
      developed. Great variations exist with regard to almost all the technical
      features, yielding a reported fat graft survivability that ranges from 40% to
      80%. Recent bench approaches have been proposed to improve the long-term
      viability of fat grafts: although promising results have been shown, empirical
      evidence has yet to prove the superiority of one particular method. Nevertheless,
      currently available literature still provides some evidence for optimal results
      in differing clinical scenarios, in the wait of validating and ultimate
      studies.The issues of enriched fat grafting techniques and variations in
      harvesting and delivery in the background of US regulatory constraints demand
      alterations and variations in techniques. These only complicate the process of
      validation of any single technique. However, recent studies have brought us
      closer to making informed decisions on technical choices in lipotransfer. These
      are elaborated on in this review. 

PMID- 24732079
TI  - Complex ventral hernia repair using components separation with or without
      biologic mesh: a cost-utility analysis: reply.

PMID- 24732080
TI  - Comparison of outcomes after TURP versus photoselective vaporization of the
      prostate with respect to trainee involvement utilizing ACS NSQIP.
AB  - BACKGROUND: Large multicenter studies comparing outcomes between TURP and
      photoselective vaporization of the prostate (PVP) are sparse, with no studies
      having compared the influence of trainee involvement on these outcomes. Our
      objectives were to assess 30-day outcomes after TURP and PVP with respect to
      trainee involvement using an independent national surgical database. METHODS:
      Using the American College of Surgeons National Surgical Quality Improvement
      Program (ACS NSQIP) data (2005-2011), 7893 men were identified who underwent TURP
      or PVP. Regression models were constructed to assess associations between
      surgical approach, risk-adjusted morbidity and individual complications.
      Relationships between operative approach, operative duration and duration of stay
      were also examined and subdivided based upon trainee level. RESULTS: Of 7893
      patients, 4950 (62.7%) underwent TURP and 2943 (37.3%) underwent PVP. TURP
      patients were older, more likely to have diabetes, cancer, history of steroid use
      and preoperative transfusion compared with PVP patients, who were more likely to
      have coronary artery disease or bleeding disorders. Risk-adjusted overall
      morbidity was similar; however, PVP was associated with less pneumonia (0.2% vs
      0.5%, P<0.015), bleeding requiring transfusion (0.5% vs 1.8%, P<0.001) and return
      to the operating room (1.5% vs 2.2%, P<0.022). PVP patients also had shorter
      length of stay (0.8 vs 2.1 days, P<0.001). There were no significant differences
      in outcomes when a trainee was involved. Operative duration was similar for TURP
      and PVP when performed by an attending alone (52 vs 52 min, P<0.001), but was
      longer with trainee involvement, regardless of post-graduate year (PGY) level
      (P<0.001). Comparison of operative duration among trainee subgroups demonstrated
      longer operative times for the PGY 6-9 subgroup performing PVP when compared with
      other subgroups (P<0.003). CONCLUSIONS: Within ACS NSQIP hospitals, TURP and PVP
      demonstrated similar risk-adjusted overall morbidity. Despite longer operative
      times for TURP and PVP with trainee involvement, there were no significant
      differences in outcomes.

PMID- 24732081
TI  - Outcomes of one-step incomplete and complete excavation in primary teeth: a 24
      month randomized controlled trial.
AB  - AIM: To compare 24-month pulp health outcomes of partial caries removal (PCR) and
      total caries removal (TCR) with composite restoration in primary molars. METHODS:
      48 children aged 3-8 years with at least one molar with a deep carious lesion
      were included. 120 teeth were randomized to control (TCR; n = 54; 69% class II)
      and test (PCR; n = 66; 63% class II) groups. Total absence of carious tissue was
      confirmed using a blunt-tipped probe in the TCR group. For PCR, excavation was
      stopped when hardened, dried dentin with a leathery consistency was achieved.
      Pulpotomy was performed in cases of pulp exposure. RESULTS: Pulp exposure
      occurred in 2 and 27.5% of teeth treated with PCR and TCR, respectively (p <
      0.01). The operative time was significantly higher for TCR than PCR. Success
      rates were 92 and 96% in the PCR and TCR groups, respectively (p = 0.34). The
      success rate tended to be lower in occlusoproximal (92%) than in occlusal (100%)
      lesions (p = 0.08). CONCLUSION: The clinical and radiographic success rates of
      PCR and TCR in primary teeth with deep carious lesions were high and did not
      differ significantly, indicating that PCR is a reliable minimally invasive
      approach in primary teeth and that the retention of carious dentin does not
      interfere with pulp vitality. Moreover, PCR provided other clinically relevant
      advantages over TCR, especially lower incidence of pulp exposure and lower
      operative time.

PMID- 24732082
TI  - Rosiglitazone did not induce acute kidney injury in normocholesterolemic rats
      despite reduction in glomerular filtration rate.
AB  - BACKGROUND/AIMS: Rosiglitazone (RGL) has been used to ameliorate lipids
      homeostasis and also to treat inflammatory diseases. However, RGL may reduce
      renal blood flow and glomerular filtration rate (GFR) predisposing to acute
      kidney injury (AKI). We investigated whether the treatment with RGL induces AKI
      in normocholesterolemic (NC) and hypercholesterolemic (HC) rats. METHODS: We
      measured GFR by inulin clearance technique and we quantified urinary neutrophil
      gelatinase-associated lipocalin (uNGAL) in all groups at baseline and during Ang
      II-stimulated vasoconstriction. Moreover, we evaluated the presence of renal
      damaged by histologic examination. RESULTS: At baseline, NC and HC had normal and
      similar GFR. RGL treatment reduced GFR only in NC+RGL. Unexpectedly, HC+RGL
      showed high levels of uNGAL although GFR was at normal range. During Ang II
      stimulated vasoconstriction, all groups showed reduction in GFR to the same range
      and we found high levels of uNGAL and high score of renal damage in HC and
      HC+RGL. CONCLUSION: RGL acts distinctly in normocholesterolemia and in
      hypercholesterolemia. Reduction in GFR provoked by RGL treatment did not allow
      the diagnosis of AKI in NC even in the presence of ANG II-stimulated
      vasoconstriction. However, AKI was diagnosed in HC+RGL at baseline although GFR
      was within normal range.

PMID- 24732083
TI  - Dielectric response of shelled toroidal particles carrying localized surface
      charge distributions. The effect of concentric and confocal shells.
AB  - Dielectric models of biological cells are generally based on spherical or
      ellipsoidal geometries, where the different adjoining dielectric media are
      arranged as distinct core and shells, representing the cytosol and the cell
      membrane. For ellipsoidal particles, this approach implies the assumption of
      confocal shells that, in turn, means a cell membrane of ill-defined thickness. A
      quantitative analysis of the influence of a non-uniform thickness of the cell
      membrane has been not considered so far. In the case of a toroidal particle, this
      problem can be conveniently addressed by considering the solution of the Laplace
      equation in two different coordinate systems, i.e., toroidal coordinates
      (confocal shells and hence non-uniform thickness of the shell membrane) and
      toroidal polar coordinate, (concentric shells and hence a uniform thickness of
      the shell membrane). In the present paper, we compare the dielectric spectra of a
      toroidal particle aqueous suspension obtained from the two above stated solutions
      of the Laplace equation and we furnish a first quantitative estimate of the
      differences arising from considering the presence of confocal or concentric
      shells. This approach offers a complete view of the influence of the membrane
      thickness on the whole dielectric spectrum of a biological particle suspension,
      at least as far as toroidal objects are concerned. 

PMID- 24732084
TI  - Impact of EU flavoured tobacco ban on waterpipe smoking.

PMID- 24732085
TI  - Bioprosthetic aortic valve replacement on a mechanical valve ring.
AB  - Mechanical valve failure is a known but rare occurrence in cardiac surgery. A 71
      year-old lady underwent surgery for failure of her mechanical aortic valve. It
      was replaced with another mechanical valve. However, during operative
      manipulation, both leaflets fractured, resulting in a prolonged operative time.
      Under these circumstances, a novel approach was adopted and a bioprosthetic valve
      was implanted on the mechanical valve sewing ring as a final resort. The
      intervention was successful. This illustrates a case of the need for innovative
      approaches in cardiac surgery. 

PMID- 24732086
TI  - Aortic valve replacement in a patient with left ventricular noncompaction.
AB  - Left ventricular noncompaction is a rare cardiac pathology that results from an
      arrest in endomyocardial development in early embryogenesis. With great advances
      in imaging modalities, this pathological entity has been noted not only in the
      pediatric population but also in adults. Herein we report the case of a 62-year
      old woman who successfully underwent aortic valve replacement for aortic
      regurgitation complicated by left ventricular noncompaction. 

PMID- 24732087
TI  - Management of abdominal stent graft infection with cryopreserved aortic
      allograft.

PMID- 24732088
TI  - Bilateral axillary artery aneurysms after Bentall procedure in Marfan syndrome.
AB  - A man with Marfan syndrome underwent a Bentall procedure for annuloaortic ectasia
      and severe aortic regurgitation at 43 years of age. Twenty-eight years after the
      Bentall procedure, he developed bilateral axillary artery aneurysms (length *
      diameter: right: 80 * 39 mm; left: 103 * 45 mm). Aneurysmectomy and
      reconstruction of the axillary artery were performed using an artificial vascular
      graft. Histological examination revealed cystic medial necrosis. The
      postoperative course was uneventful, but long-term follow-up is necessary. 

PMID- 24732089
TI  - Superior vena cava obstruction after heart transplantation.
AB  - Superior vena cava obstruction can be a serious complication after heart
      transplantation. A 58-year-old man with ischemic cardiomyopathy underwent
      orthotopic bicaval heart transplantation. On the 12th postoperative day, one hour
      after removing the central venous line, he developed sudden onset of facial
      edema, cyanosis, and tachycardia. Emergency transesophageal echocardiography
      revealed superior vena caval thrombosis at the site of anastomosis. Considering
      the risks of surgical reexploration, the superior vena cava was recanalized by
      stent deployment. All of the patient's symptoms were relieved a few hours after
      stent placement. 

PMID- 24732090
TI  - Electrophysiological responses to alcohol cues are not associated with Pavlovian
      to-instrumental transfer in social drinkers.
AB  - Pavlovian to Instrumental Transfer (PIT) refers to the behavioral phenomenon of
      increased instrumental responding for a reinforcer when in the presence of
      Pavlovian conditioned stimuli that were separately paired with that reinforcer.
      PIT effects may play an important role in substance use disorders, but little is
      known about the brain mechanisms that underlie these effects in alcohol
      consumers. We report behavioral and electroencephalographic (EEG) data from a
      group of social drinkers (n = 31) who performed a PIT task in which they chose
      between two instrumental responses in pursuit of beer and chocolate reinforcers
      while their EEG reactivity to beer, chocolate and neutral pictorial cues was
      recorded. We examined two markers of the motivational salience of the pictures:
      the P300 and slow wave event-related potentials (ERPs). Results demonstrated a
      behavioral PIT effect: responding for beer was increased when a beer picture was
      presented. Analyses of ERP amplitudes demonstrated significantly larger slow
      potentials evoked by beer cues at various electrode clusters. Contrary to
      hypotheses, there were no significant correlations between behavioral PIT
      effects, electrophysiological reactivity to the cues, and individual differences
      in drinking behaviour. Our findings are the first to demonstrate a PIT effect for
      beer, accompanied by increased slow potentials in response to beer cues, in
      social drinkers. The lack of relationship between behavioral and EEG measures,
      and between these measures and individual differences in drinking behaviour may
      be attributed to methodological features of the PIT task and to characteristics
      of our sample. 

PMID- 24732091
TI  - Comparison of liver fat indices for the diagnosis of hepatic steatosis and
      insulin resistance.
AB  - CONTEXT: Hepatic steatosis, defined as increased hepatocellular lipid content
      (HCL), associates with visceral obesity and glucose intolerance. As exact HCL
      quantification by 1H-magnetic resonance spectroscopy (1H-MRS) is not generally
      available, various clinical indices are increasingly used to predict steatosis.
      OBJECTIVE: The purpose of this study was to test the accuracy of NAFLD liver fat
      score (NAFLD-LFS), hepatic steatosis index (HSI) and fatty liver index (FLI)
      against 1H-MRS and their relationships with insulin sensitivity and secretion.
      DESIGN, SETTING AND PARTICIPANTS: Ninety-two non-diabetic, predominantly non
      obese humans underwent clinical examination, 1H-MRS and an oral glucose tolerance
      test (OGTT) to calculate insulin sensitivity and beta-cell function. Accuracy of
      indices was assessed from the area under the receiver operating characteristic
      curve (AROC). RESULTS: Median HCL was 2.49% (0.62;4.23) and correlated with
      parameters of glycemia across all subjects. NAFLD-LFS, FLI and HSI yielded AROCs
      of 0.70, 0.72, and 0.79, respectively, and related positively to HCL, insulin
      resistance, fasting and post-load beta-cell function normalized for insulin
      resistance. Upon adjustment for age, sex and HCL, regression analysis revealed
      that NAFLD-LFS, FLI and HSI still independently associated with both insulin
      sensitivity and beta-cell function. CONCLUSION: The tested indices offer modest
      efficacy to detect steatosis and cannot substitute for fat quantification by 1H
      MRS. However, all indices might serve as surrogate parameters for liver fat
      content and also as rough clinical estimates of abnormal insulin sensitivity and
      secretion. Further validation in larger collectives such as epidemiological
      studies is needed.

PMID- 24732092
TI  - Spores of Clostridium engineered for clinical efficacy and safety cause
      regression and cure of tumors in vivo.
AB  - Spores of some species of the strictly anaerobic bacteria Clostridium naturally
      target and partially lyse the hypoxic cores of tumors, which tend to be
      refractory to conventional therapies. The anti-tumor effect can be augmented by
      engineering strains to convert a non-toxic prodrug into a cytotoxic drug
      specifically at the tumor site by expressing a prodrug-converting enzyme (PCE).
      Safe doses of the favored prodrug CB1954 lead to peak concentrations of 6.3 uM in
      patient sera, but at these concentration(s) known nitroreductase (NTR) PCEs for
      this prodrug show low activity. Furthermore, efficacious and safe Clostridium
      strains that stably express a PCE have not been reported. Here we identify a
      novel nitroreductase from Neisseria meningitidis, NmeNTR, which is able to
      activate CB1954 at clinically-achievable serum concentrations. An NmeNTR
      expression cassette, which does not contain an antibiotic resistance marker, was
      stably localized to the chromosome of Clostridium sporogenes using a new
      integration method, and the strain was disabled for safety and containment by
      making it a uracil auxotroph. The efficacy of Clostridium-Directed Enzyme Prodrug
      Therapy (CDEPT) using this system was demonstrated in a mouse xenograft model of
      human colon carcinoma. Substantial tumor suppression was achieved, and several
      animals were cured. These encouraging data suggest that the novel enzyme and
      strain engineering approach represent a promising platform for the clinical
      development of CDEPT.

PMID- 24732093
TI  - Thalidomide, cyclophosphamide and dexamethasone induction therapy: feasibility
      for myeloma patients destined for autologous stem cell transplantation.
AB  - This study explored the effect of thalidomide and cyclophosphamide on stem cell
      collection, in addition to assessing their efficacy as induction therapy for
      myeloma patients destined for autologous stem cell transplantation (ASCT). We
      analyzed newly diagnosed myeloma patients who received TCD (thalidomide 100
      mg/day for 28 days, oral cyclophosphamide 150 mg/m 2 /day and dexamethasone 40
      mg/day on days 1-4) as induction therapy prior to ASCT. Peripheral stem cells
      were mobilized with granulocyte colony-stimulating factor and cyclophosphamide.
      Thirty-six patients (median age 54 years) received TCD chemotherapy (median 4
      cycles). The overall response rate to TCD was 77.8% (28/36). The median number of
      CD34+ cells was 6.5 * 10 6 /kg, and 2 patients failed to achieve the optimal
      number of CD34+ cells, i.e. 4.0 * 10 6 /kg, although they were able to attain
      >2.0 * 10 6 /kg. The overall response rate increased up to 94.4% (34/36) after
      ASCT; this included 9 patients with a stringent complete response without
      transplantation-related mortality. Four patients died due to disease progression
      and 17 were found to have progressed after ASCT (the median progression-free
      survival after ASCT was 19.6 months). TCD chemotherapy can be an effective and
      feasible induction regimen prior to ASCT for myeloma patients.

PMID- 24732095
TI  - Testosterone reactivity to facial display of emotions in men and women.
AB  - Previous studies have examined testosterone's role in regulating the processing
      of facial displays of emotions (FDEs). However, the reciprocal process - the
      influence of FDEs, an evolutionarily ancient and potent class of social signals,
      on the secretion of testosterone - has not yet been studied. To address this gap,
      we examined the effects of emotional content and sex of facial stimuli in
      modulating endogenous testosterone fluctuations, as well as sex differences in
      the endocrine responses to faces. One hundred and sixty-four young healthy men
      and women were exposed, in a between-subjects design, to happy or angry same-sex
      or opposite-sex facial expressions. Results showed that in both men (n=85) and
      women (n=79), extended exposure to faces of the opposite sex, regardless of their
      apparent emotional content, was accompanied by an accumulation in salivary
      testosterone when compared to exposure to faces of the same sex. Furthermore,
      testosterone change in women exposed to angry expressions was greater than
      testosterone change in women exposed to happy expressions. These results add
      emotional facial stimuli to the collection of social signals that modulate
      endocrine status, and are discussed with regard to the evolutionary roles of
      testosterone. 

PMID- 24732094
TI  - Rewiring yeast osmostress signalling through the MAPK network reveals essential
      and non-essential roles of Hog1 in osmoadaptation.
AB  - Mitogen-activated protein kinases (MAPKs) have a number of targets which they
      regulate at transcriptional and post-translational levels to mediate specific
      responses. The yeast Hog1 MAPK is essential for cell survival under hyperosmotic
      conditions and it plays multiple roles in gene expression, metabolic regulation,
      signal fidelity and cell cycle regulation. Here we describe essential and non
      essential roles of Hog1 using engineered yeast cells in which osmoadaptation was
      reconstituted in a Hog1-independent manner. We rewired Hog1-dependent osmotic
      stress-induced gene expression under the control of Fus3/Kss1 MAPKs, which are
      activated upon osmostress via crosstalk in hog1Delta cells. This approach
      revealed that osmotic up-regulation of only two Hog1-dependent glycerol
      biosynthesis genes, GPD1 and GPP2, is sufficient for successful osmoadaptation.
      Moreover, some of the previously described Hog1-dependent mechanisms appeared to
      be dispensable for osmoadaptation in the engineered cells. These results suggest
      that the number of essential MAPK functions may be significantly smaller than
      anticipated and that knockout approaches may lead to over-interpretation of
      phenotypic data. 

PMID- 24732097
TI  - Post-traumatic humero-ulnar synostosis.
AB  - A humero-ulnar synostosis is a bony connection between the humerus and the ulna.
      This is a very rare finding and it results in a serious disability of the elbow.
      Usually, a synostosis of the elbow occurs as a congenital anomaly. In this case,
      a 6-year-old girl was seen with a post-traumatic humero-ulnar synostosis, which
      has never been reported in the literature before. Surgical resection of the
      humero-ulnar synostosis was performed. Along with rapid intensive physical
      therapy, almost full recovery of function was achieved. The short-term result is
      very satisfactory, but the long-term results and recurrence rate are still
      unknown.

PMID- 24732096
TI  - BCL10 regulates RNF8/RNF168-mediated ubiquitination in the DNA damage response.
AB  - Timely and proper cellular response to DNA damage is essential for maintenance of
      genome stability and integrity. B-cell lymphoma/leukemia 10 (BCL10) facilitates
      ubiquitination of NEMO in the cytosol, activating NFkappaB signaling.
      Translocation and/or point mutations of BCL10 associate with mucosa-associated
      lymphoid tissue lymphomas and other malignancies. However, the mechanisms by
      which the resulting aberrant expression of BCL10 leads to cellular oncogenesis
      are poorly understood. In this report, we found that BCL10 in the nucleus is
      enriched at the DNA damage sites in an ATM- and RNF8-dependent manner. ATM
      dependent phosphorylation of BCL10 promotes its interaction with and presentation
      of UBC13 to RNF8, and RNF8-mediated ubiquitination of BCL10 enhances binding of
      BCL10 and UBC13 to RNF168. This allows mono-ubiquitination on H2AX by RNF168 and
      further poly-ubiquitination by the RNF8/RNF168-containing complex. Depletion of
      BCL10 compromised homology recombination-mediated DNA double-strand break (DSB)
      repair because of insufficient recruitment of BRCA1, RAD51, and the ubiquitinated
      DNA damage response factors. Taken together, our results demonstrate a novel
      function of BCL10 in delivering UBC13 to RNF8/RNF168 to regulate ubiquitination
      mediated DSB signaling and repair. 

PMID- 24732098
TI  - Collaborative virtual reality based advanced cardiac life support training
      simulator using virtual reality principles.
AB  - BACKGROUND: Advanced Cardiac Life Support (ACLS) is a series of team-based,
      sequential and time constrained interventions, requiring effective communication
      and coordination of activities that are performed by the care provider team on a
      patient undergoing cardiac arrest or respiratory failure. The state-of-the-art
      ACLS training is conducted in a face-to-face environment under expert supervision
      and suffers from several drawbacks including conflicting care provider schedules
      and high cost of training equipment. OBJECTIVE: The major objective of the study
      is to describe, including the design, implementation, and evaluation of a novel
      approach of delivering ACLS training to care providers using the proposed virtual
      reality simulator that can overcome the challenges and drawbacks imposed by the
      traditional face-to-face training method. METHODS: We compare the efficacy and
      performance outcomes associated with traditional ACLS training with the proposed
      novel approach of using a virtual reality (VR) based ACLS training simulator. One
      hundred and forty-eight (148) ACLS certified clinicians, translating into 26 care
      provider teams, were enrolled for this study. Each team was randomly assigned to
      one of the three treatment groups: control (traditional ACLS training),
      persuasive (VR ACLS training with comprehensive feedback components), or
      minimally persuasive (VR ACLS training with limited feedback components). The
      teams were tested across two different ACLS procedures that vary in the degree of
      task complexity: ventricular fibrillation or tachycardia (VFib/VTach) and
      pulseless electric activity (PEA). RESULTS: The difference in performance between
      control and persuasive groups was not statistically significant (P=.37 for PEA
      and P=.1 for VFib/VTach). However, the difference in performance between control
      and minimally persuasive groups was significant (P=.05 for PEA and P=.02 for
      VFib/VTach). The pre-post comparison of performances of the groups showed that
      control (P=.017 for PEA, P=.01 for VFib/VTach) and persuasive (P=.02 for PEA,
      P=.048 for VFib/VTach) groups improved their performances significantly, whereas
      minimally persuasive group did not (P=.45 for PEA, P=.46 for VFib/VTach). Results
      also suggest that the benefit of persuasiveness is constrained by the potentially
      interruptive nature of these features. CONCLUSIONS: Our results indicate that the
      VR-based ACLS training with proper feedback components can provide a learning
      experience similar to face-to-face training, and therefore could serve as a more
      easily accessed supplementary training tool to the traditional ACLS training. Our
      findings also suggest that the degree of persuasive features in VR environments
      have to be designed considering the interruptive nature of the feedback elements.

PMID- 24732099
TI  - A secure-enhanced data aggregation based on ECC in wireless sensor networks.
AB  - Data aggregation is an important technique for reducing the energy consumption of
      sensor nodes in wireless sensor networks (WSNs). However, compromised aggregators
      may forge false values as the aggregated results of their child nodes in order to
      conduct stealthy attacks or steal other nodes' privacy. This paper proposes a
      Secure-Enhanced Data Aggregation based on Elliptic Curve Cryptography (SEDA-ECC).
      The design of SEDA-ECC is based on the principles of privacy homomorphic
      encryption (PH) and divide-and-conquer. An aggregation tree disjoint method is
      first adopted to divide the tree into three subtrees of similar sizes, and a PH
      based aggregation is performed in each subtree to generate an aggregated subtree
      result. Then the forged result can be identified by the base station (BS) by
      comparing the aggregated count value. Finally, the aggregated result can be
      calculated by the BS according to the remaining results that have not been
      forged. Extensive analysis and simulations show that SEDA-ECC can achieve the
      highest security level on the aggregated result with appropriate energy
      consumption compared with other asymmetric schemes. 

PMID- 24732100
TI  - Modeling and manufacturing of a micromachined magnetic sensor using the CMOS
      process without any post-process.
AB  - The modeling and fabrication of a magnetic microsensor based on a magneto
      transistor were presented. The magnetic sensor is fabricated by the commercial
      0.18 mm complementary metal oxide semiconductor (CMOS) process without any post
      process. The finite element method (FEM) software Sentaurus TCAD is utilized to
      analyze the electrical properties and carriers motion path of the magneto
      transistor. A readout circuit is used to amplify the voltage difference of the
      bases into the output voltage. Experiments show that the sensitivity of the
      magnetic sensor is 354 mV/T at the supply current of 4 mA. 

PMID- 24732101
TI  - Object detection techniques applied on mobile robot semantic navigation.
AB  - The future of robotics predicts that robots will integrate themselves more every
      day with human beings and their environments. To achieve this integration, robots
      need to acquire information about the environment and its objects. There is a big
      need for algorithms to provide robots with these sort of skills, from the
      location where objects are needed to accomplish a task up to where these objects
      are considered as information about the environment. This paper presents a way to
      provide mobile robots with the ability-skill to detect objets for semantic
      navigation. This paper aims to use current trends in robotics and at the same
      time, that can be exported to other platforms. Two methods to detect objects are
      proposed, contour detection and a descriptor based technique, and both of them
      are combined to overcome their respective limitations. Finally, the code is
      tested on a real robot, to prove its accuracy and efficiency. 

PMID- 24732102
TI  - Spatial estimation of sub-hour Global Horizontal Irradiance based on official
      observations and remote sensors.
AB  - This study was motivated by the need to improve densification of Global
      Horizontal Irradiance (GHI) observations, increasing the number of surface
      weather stations that observe it, using sensors with a sub-hour periodicity and
      examining the methods of spatial GHI estimation (by interpolation) with that
      periodicity in other locations. The aim of the present research project is to
      analyze the goodness of 15-minute GHI spatial estimations for five methods in the
      territory of Spain (three geo-statistical interpolation methods, one
      deterministic method and the HelioSat2 method, which is based on satellite
      images). The research concludes that, when the work area has adequate station
      density, the best method for estimating GHI every 15 min is Regression Kriging
      interpolation using GHI estimated from satellite images as one of the input
      variables. On the contrary, when station density is low, the best method is
      estimating GHI directly from satellite images. A comparison between the GHI
      observed by volunteer stations and the estimation model applied concludes that
      67% of the volunteer stations analyzed present values within the margin of error
      (average of +/-2 standard deviations). 

PMID- 24732103
TI  - Heterologous production of the lipopeptide biosurfactant serrawettin W1 in
      Escherichia coli.
AB  - The non-ionic biosurfactant serrawettin W1 is a lipopeptide produced by red
      pigmented strains of Serratia marcescens which shows antimicrobial, antitumor and
      plant protecting properties. Here, we report a simple method for heterologous
      production of this biosurfactant. S. marcescens strain DSM12481 was identified as
      a novel serrawettin W1 producer and the respective nonribosomal peptide
      synthetase gene swrW was cloned and expressed in Escherichia coli BL21 Gold.
      Chemical analysis of heterologous serrawettin W1 revealed that E. coli mainly
      produced serrawettin with C10 fatty acids as does S. marcescens. Additionally,
      serrawettin species with longer fatty acids (C13, C14) were detected in S.
      marcescens which were absent in E. coli. The expression system described here
      paves the way for the large scale production of this biotechnologically important
      biosurfactant. 

PMID- 24732105
TI  - Role of growth hormone in enchondroplasia and chondral osteogenesis: evaluation
      by X-ray of the hand.
AB  - BACKGROUND: The process of growth and maturation of long (radius and ulna) and
      short (metacarpals and phalanges) bones of the hand (enchondroplasia) differs
      from that of the carpal cuboid bones (chondral osteogenesis). This study aimed to
      assess the impact of growth hormone (GH) on these two processes of bone
      maturation. METHODS: Subjects of the study were 95 prepubertal children: 30
      children with GH deficiency and 65 children with idiopathic short stature, aged
      7.4 +/- 1.9 y (mean +/- SD) (trial registration number 98-0198-033). Bone
      maturation was assessed by the Greulich and Pyle method from X-rays obtained at
      the start and at 1 and 2 y of GH treatment, separately for carpals, long bones,
      and short bones, and was expressed as years of delay relative to chronological
      age. RESULTS: At GH start, the delay in bone maturation in the GH-deficient group
      was significantly greater for carpals (3.6 +/- 1.3 y) than for long (3.0 +/- 1.3
      y) and short (1.7 +/- 1.1 y) bones. The delay was nonsignificantly greater for
      carpal bones in GH-deficient subjects than in subjects with idiopathic short
      stature (3.6 +/- 1.3 vs. 3.1 +/- 1.1 y, respectively) and was normalized after 2
      y of GH treatment. CONCLUSION: The dominant effect of GH was on chondral
      osteogenesis, with milder effect on enchondroplasia. A distinct delay in carpal
      and long-bone maturation, which normalizes during 2 y of GH treatment, was
      typical in GH-deficient children. Therefore, separate carpal bone assessment in
      bone age reading is needed.

PMID- 24732104
TI  - Cytokines associated with necrotizing enterocolitis in extremely-low-birth-weight
      infants.
AB  - BACKGROUND: The goal was to identify cytokines associated with necrotizing
      enterocolitis (NEC). Based on our earlier reports of decreased tissue expression
      of transforming growth factor (TGF)-beta, we hypothesized that infants with NEC
      also have low blood TGF-beta levels. We further hypothesized that because fetal
      inflammation increases the risk of NEC, infants who develop NEC have elevated
      blood cytokine levels in early neonatal period. METHODS: Data on 104 extremely
      low-birth-weight infants with NEC and 893 without NEC from 17 centers were
      analyzed. Clinical information was correlated with blood cytokine levels on
      postnatal day 1 (D1), D3, D7, D14, and D21. RESULTS: Male gender, non
      Caucasian/non-African American ethnicity, sepsis, lower blood TGF-beta and
      interleukin (IL)-2 levels, and higher IL-8 levels were associated with NEC. The
      NEC group had lower TGF-beta levels than controls since D1. The diagnosis of NEC
      was associated with elevated IL-1beta, IL-6, IL-8, IL-10, monocyte
      chemoattractant protein-1/CC-motif ligand-2, macrophage inflammatory protein
      1beta/CC-motif ligand-3, and C-reactive protein. CONCLUSION: Clinical
      characteristics, such as gender and ethnicity, and low blood TGF-beta levels are
      associated with higher risk of NEC. Infants who developed NEC did not start with
      high blood levels of inflammatory cytokines, but these rose mainly after the
      onset of NEC.

PMID- 24732106
TI  - The human gut microbiota: a dynamic interplay with the host from birth to
      senescence settled during childhood.
AB  - The microbiota "organ" is the central bioreactor of the gastrointestinal tract,
      populated by a total of 10(14) bacteria and characterized by a genomic content
      (microbiome), which represents more than 100 times the human genome. The
      microbiota plays an important role in child health by acting as a barrier against
      pathogens and their invasion with a highly dynamic modality, exerting metabolic
      multistep functions and stimulating the development of the host immune system,
      through well-organized programming, which influences all of the growth and aging
      processes. The advent of "omics" technologies (genomics, proteomics,
      metabolomics), characterized by complex technological platforms and advanced
      analytical and computational procedures, has opened new avenues to the knowledge
      of the gut microbiota ecosystem, clarifying some aspects on the establishment of
      microbial communities that constitute it, their modulation and active interaction
      with external stimuli as well as food, within the host genetic variability. With
      a huge interdisciplinary effort and an interface work between basic,
      translational, and clinical research, microbiologists, specialists in "-omics"
      disciplines, and clinicians are now clarifying the role of the microbiota in the
      programming process of several gut-related diseases, from the physiological
      symbiosis to the microbial dysbiosis stage, through an integrated systems biology
      approach. 

PMID- 24732107
TI  - Administration of antenatal glucocorticoids and postnatal surfactant ameliorates
      respiratory distress syndrome-associated neonatal lethality in Erk3(-/-) mouse
      pups.
AB  - BACKGROUND: Respiratory distress syndrome (RDS) persists as a prevalent cause of
      infant morbidity and mortality. We have previously demonstrated that deletion of
      Erk3 results in pulmonary immaturity and neonatal lethality. Using RNA
      sequencing, we identified corticotrophin releasing hormone (CRH) and surfactant
      protein B (SFTPB) as potential molecular mediators of Erk3-dependent lung
      maturation. In this study, we characterized the impact of antenatal
      glucocorticoids and postnatal surfactant on neonatal survival of Erk3 null mice.
      METHODS: In a double crossover design, we administered dexamethasone (dex) or
      saline to pregnant dams during the saccular stage of lung development, followed
      by postnatal surfactant or saline via inhalation intubation. Survival was
      recorded, and detailed lung histological analysis and staining for CRH and SFTPB
      protein expression were performed. RESULTS: Without treatment, Erk3 null pups die
      within 6 h of birth with reduced aerated space, impaired thinning of the alveolar
      septa, and abundant glycogen stores, as described in human RDS. The
      administration of dex and surfactant improved RDS-associated lethality of Erk3(-/
      ) pups and partially restored functional fetal lung maturation by accelerating
      the downregulation of pulmonary CRH and partially rescuing the production of
      SFTPB. CONCLUSION: These findings emphasize that Erk3 is integral to terminal
      differentiation of type II cells, SFTPB production, and fetal pulmonary maturity.

PMID- 24732108
TI  - Dose and detectability improvements with high energy phase sensitive x-ray
      imaging in comparison to low energy conventional imaging.
AB  - The objective of this study was to demonstrate the potential benefits of using
      high energy x-rays for phase sensitive breast imaging through a comparison with
      conventional mammography imaging. We compared images of a contrast-detail phantom
      acquired on a prototype phase sensitive x-ray imaging system with images acquired
      on a commercial flat panel digital mammography unit. The phase contrast images
      were acquired using a micro-focus x-ray source with a 50 um focal spot at 120 kVp
      and 4.5 mAs, with a magnification factor of 2.46 and a 50 um pixel pitch. A phase
      attenuation duality-based phase retrieval algorithm that requires only a single
      phase contrast image was applied. Conventional digital mammography images were
      acquired at 27 kVp, 131 mAs and 28 kVp, 54 mAs. For the same radiation dose, both
      the observer study and signal-to-noise ratio (SNR)/figure of merit comparisons
      indicated a large improvement by the phase retrieved image as compared to the
      clinical system for the larger disc sizes, but the improvement was not enough to
      detect the smallest discs. Compared to the double dose image acquired with the
      clinical system, the observer study also indicated that the phase retrieved image
      provided improved detection capabilities for all disc sizes except the smallest
      discs. Thus the SNR improvement provided by phase contrast imaging is not yet
      enough to offset the noise reduction provided by the clinical system at the
      doubled dose level. However, the potential demonstrated by this study for high
      energy phase sensitive x-ray imaging to improve lesion detection and reduce
      radiation dose in mammography warrants further investigation of this technique. 

PMID- 24732109
TI  - Sleep measures expressing 'functional uncertainty' in elderlies' sleep.
AB  - BACKGROUND: The notion of 'functional uncertainty' during sleep was first
      proposed to indicate an inability of the central nervous system to maintain
      stable states by coordinating physiological processes. While the presence of
      functional uncertainty phenomena has been shown in infants and hypothesized in
      the elderly, its actual occurrence in the aged population has never been
      systematically investigated. OBJECTIVE: The aim of the study is to identify, in
      the sleep of aged individuals, indexes of sleep instability and fragmentation as
      markers of functional uncertainty, by comparing a sample of healthy elderly
      subjects to one of young adults. METHODS: We compared polysomnograhic recordings
      of 20 healthy elderly subjects (age range 65-85 years) with those of 20 young
      individuals (age range 22-32 years), with special regard to the variables
      expressing functional uncertainty in sleep, such as continuity (e.g. arousals,
      awakenings), stability (e.g. state transitions, periods of marked 'functional
      uncertainty') and cyclic organization parameters. RESULTS: Significant
      differences emerged for all variables of interest: the elderly group showed
      higher indexes of fragmentation and instability than the young, as well as less
      and shorter cycles, and a lower percentage of time spent in cycles. CONCLUSION:
      Our results support the hypothesis of a progressive sleep quality disruption with
      aging, expressed by pronounced sleep instability, fragmentation and
      disorganization. We propose that functional uncertainty measures could usefully
      be included in standard sleep assessments on both aged and sleep-disordered
      populations as accurate sleep quality indexes.

PMID- 24732110
TI  - Effects of deer velvet extract from Formosan sika deer on the embryonic
      development and anti-oxidative enzymes mRNA expression in mouse embryos.
AB  - ETHNOPHARMACROLOGICAL RELEVANCE: The deer velvet or its extracts has been widely
      used in clinic. It has been used in promoting reproductive performances and
      treating of oxidation and aging process. The aim of this study is to investigate
      the effects of velvet extract from Formosan sika deer (Formosan sika deer; Cervus
      nippon taiouanus, FSD) velvet on mouse embryonic development and anti-oxidant
      ability in vitro. MATERIALS AND METHODS: Mouse 4-cells embryos were divided into
      16 groups for 72 h in vitro incubation. The embryonic development stages and
      morphology were evaluated every 12h in experimental period. The quantitative real
      time PCR was used to measure the CuZn-SOD, GPx and CAT mRNA expression of the
      blastocysts. RESULTS: The 4-cells embryos of hydrogen peroxide (HP) groups did
      not continue developing after oxidant stress challenged. The blastocyst
      developmental rate (90.0-90.4%, P>0.05) and normal morphological rate (84.4
      85.1%, P>0.05) of the 1% and 2% DV extract groups were similar to those in the
      control group (90.7% and 88.8%, respectively). The embryos challenged by HP (5,
      10 and 25 MUM) and subsequently incubated in mHTF medium with 1% and 2% of deer
      velvet (DV) extracts were able to continue development; the blastocyst
      developmental rate of these groups were similar to that in the control group. The
      relative mRNA expression of the focused anti-oxidative enzymes in the mouse
      embryos did not significantly differ among the designed DV treatment groups
      (P>0.05). CONCLUSION: The FSD velvet extract in adequate concentration could
      promote anti-oxidative enzymes mRNA expression followed the challenge of hydrogen
      peroxide, relieve the mouse embryo under oxidative stress, and maintain the
      blastocyst developmental ability in vitro.

PMID- 24732111
TI  - Hydnocarpus: an ethnopharmacological, phytochemical and pharmacological review.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: The genus Hydnocarpus (Flacourtiaceae) includes
      forty species that are spread across the globe. In the Indian System of Medicine,
      Hydnocarpus pentandrus (Buch.-Ham.) Oken. is primarily used for treating leprosy
      and other skin disorders. It is known as "Chaulmoogra" and is also used to treat
      other indications including constipation, inflammation, blood disorders, and worm
      infestations. Various species of Hydnocarpus are also used in traditional
      medicine in China, Thailand, Malaysia, and Myanmar for several skin disorders. To
      assess the therapeutic potential of species from the Hydnocarpus genus and to
      determine future avenues for research. METHODS: All relevant scientific
      literature published up to the end of December 2013 was retrieved via a library
      and electronic search (SciFinder, PubMed, ScienceDirect, and Google Scholar).
      Manual searches of traditional books like to ancient classics, including Vaidya
      Yoga Ratnavali, Siddha Materia Medica, and contemporary references including The
      Ayurvedic Pharmacopoeia of India and The Ayurveda Formulary, were also performed.
      RESULTS: Seed oil from species of the Hydnocarpus genus is used for medicinal
      purposes, predominantly for various skin disorders. This oil is reported to
      contain a characteristic class of compounds known as cyclopentenyl fatty acids.
      Furthermore, seeds of this genus are reported to contain triglycerides of fatty
      acids, sterols, flavonoids, and flavonolignans. Hydnocarpin, a flavonolignan, is
      reported to potentiate antimicrobial and anticancer activity. The extracts and
      compounds isolated from this plant show a wide spectrum of pharmacological
      properties, including antibacterial, antileprotic, antitubercular, antipsoriatic,
      antirheumatic, hypolipidemic, antidiabetic, anticancer, anti-inflammatory, and
      antioxidant activities. The antileprotic activity is postulated to be due to the
      cyclopentenyl fatty acids present in the seed oil. CONCLUSION: Flavonolignans
      have an interesting chemical motif, and hydnocarpin and its congeners should be
      investigated for their activities and the mechanism underlying these activities.
      Multi-drug-resistant microbes are on the increase, and the possible inhibitory
      effect of these compounds when used with current antimicrobials should also be
      evaluated. Furthermore, unique cyclopentenyl fatty acids should also be
      investigated to understand the exact mechanism of action underlying antileprotic
      activity. Additional in depth phytochemical investigations of seed oil and
      extracts are required to tap the true potential of species from the Hydnocarpus
      genus.

PMID- 24732112
TI  - Ocimum sanctum leaf extracts attenuate human monocytic (THP-1) cell activation.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Ocimum sanctum (OS), commonly known as Holy
      basil/Tulsi, has been traditionally used to treat cardiovascular diseases (CVD)
      and manage general cardiac health. The present study is designed to evaluate the
      antiinflammatory effect of O. sanctum and its phenolic compound and eugenol (EUG)
      in human monocytic (THP-1) cells and validate its traditional use for treating
      cardiovascular diseases. MATERIALS AND METHODS: The phytochemical analysis of
      alcoholic and water extracts of OS-dry leaves (OSAE and OSWE) was done using LC
      QTOF-MS. A phenolic compound, EUG was quantified in both OSAE and OSWE by an LC
      MS technique using a mass hunter work station software quantitative analysis
      system. The effect of both OSAE, OSWE, pure compound EUG and positive control
      imatinib (IMT) was investigated in THP-1 cells by studying the following markers:
      lipopolysaccharide (LPS) induced tumor necrosis factor alpha (TNF-alpha)
      secretion by ELISA, gene expression of inflammatory markers (TNF-alpha, IL-6, MIP
      1alpha and MCP-1) by real time PCR and translocation of nuclear factor kappa B
      (NF-kappaB) by confocol microscopy. Furthermore, the effect of the extracts, EUG
      and IMT, was studied on phorbol-12-myristate-13-acetate (PMA) induced monocyte to
      macrophage differentiation and gene expression of CD14, TLR2 and TLR4. RESULTS:
      The LC-MS analysis of OSAE and OSWE revealed the presence of several bioactive
      compounds including eugenol. Quantitative analysis revealed that OSAE and OSWE
      had EUG of 12 ng/mgdwt and 19 ng/mgdwt respectively. OSAE, OSWE (1 mg dwt/mL)
      pure compound EUG (60 ug/mL) and positive control IMT (20 ug/mL) showed marked
      inhibition on LPS induced TNF-alpha secretion by THP-1 cells. At the selected
      concentration, the plant extracts, EUG and IMT inhibited gene expression of
      cytokines and chemokines (IL-6, TNF-alpha, MIP-1alpha, MCP-1) and translocation
      of NF-kappaB-p65 to the nuclei. In addition, they showed significant inhibition
      on PMA induced monocyte to macrophage differentiation and the gene expression of
      CD14, TLR2 and TLR4 markers. CONCLUSION: The result of the present study
      validated traditional use of Ocimum sanctum for treating cardiovascular disease
      for the first time by testing antiinflammatory activity of Ocimum sanctum in
      acute inflammatory model, LPS induced THP-1 cells. The plant extracts showed
      significant antiinflammatory activity, however, further to be evaluated using
      chronic inflammatory animal models like diabetic or apolipoprotein E-deficient
      mice to make it evidence based medicine. The phenolic compound eugenol (60 ug/mL)
      showed significant antiinflammatory activity. However the amount of eugenol
      present in 1mg of OSAE and OSWE (12 ng/mg and 19 ng/mg dwt respectively) used for
      cell based assays was very low. It suggests that several other metabolites along
      with eugenol are responsible for the efficacy of the extracts.

PMID- 24732113
TI  - PseKNC: a flexible web server for generating pseudo K-tuple nucleotide
      composition.
AB  - The pseudo oligonucleotide composition, or pseudo K-tuple nucleotide composition
      (PseKNC), can be used to represent a DNA or RNA sequence with a discrete model or
      vector yet still keep considerable sequence order information, particularly the
      global or long-range sequence order information, via the physicochemical
      properties of its constituent oligonucleotides. Therefore, the PseKNC approach
      may hold very high potential for enhancing the power in dealing with many
      problems in computational genomics and genome sequence analysis. However, dealing
      with different DNA or RNA problems may need different kinds of PseKNC. Here, we
      present a flexible and user-friendly web server for PseKNC (at
      http://lin.uestc.edu.cn/pseknc/default.aspx) by which users can easily generate
      many different modes of PseKNC according to their need by selecting various
      parameters and physicochemical properties. Furthermore, for the convenience of
      the vast majority of experimental scientists, a step-by-step guide is provided on
      how to use the current web server to generate their desired PseKNC without the
      need to follow the complicated mathematical equations, which are presented in
      this article just for the integrity of PseKNC formulation and its development. It
      is anticipated that the PseKNC web server will become a very useful tool in
      computational genomics and genome sequence analysis.

PMID- 24732114
TI  - One-step kinetics-based immunoassay for the highly sensitive detection of C
      reactive protein in less than 30 min.
AB  - This article reveals a rapid sandwich enzyme-linked immunosorbent assay (ELISA)
      for the highly sensitive detection of human C-reactive protein (CRP) in less than
      30 min. It employs a one-step kinetics-based highly simplified and cost-effective
      sandwich ELISA procedure with minimal process steps. The procedure involves the
      formation of a sandwich immune complex on capture anti-human CRP antibody-bound
      Dynabeads in 15 min, followed by two magnet-assisted washings and one enzymatic
      reaction. The developed sandwich ELISA detects CRP in the dynamic range of 0.3 to
      81 ng ml(-1) with a limit of detection of 0.4 ng ml(-1) and an analytical
      sensitivity of 0.7 ng ml(-1). It detects CRP spiked in diluted human whole blood
      and serum with high analytical precision, as confirmed by conventional sandwich
      ELISA. Moreover, the results of the developed ELISA for the determination of CRP
      in the ethylenediaminetetraacetic acid plasma samples of patients are in good
      agreement with those obtained by the conventional ELISA. The developed
      immunoassay has immense potential for the development of rapid and cost-effective
      in vitro diagnostic kits.

PMID- 24732115
TI  - Peptide labeling with photoactivatable trifunctional cadaverine derivative and
      identification of interacting partners by biotin transfer.
AB  - A new photoactivatable trifunctional cross-linker, cBED (cadaverine-2-[6
      (biotinamido)-2-(p-azidobenzamido) hexanoamido]ethyl-1,3'-dithiopropionate), was
      synthesized by chemical conversion of sulfo-SBED (sulfosuccinimidyl-2-[6
      (biotinamido)-2-(p-azidobenzamido) hexanoamido]ethyl-1,3'-dithiopropionate) with
      cadaverine. This cross-linker was purified by reversed-phase high-performance
      liquid chromatography (RP-HPLC) and characterized using matrix-assisted laser
      desorption/ionization time-of-flight (MALDI-TOF) analysis. cBED is based on sulfo
      SBED that has a photoactivatable azido group, a cleavable disulfide bond for
      label transfer methods, and a biotin moiety for highly sensitive biotin/avidin
      detection. By ultraviolet (UV) light, the azido group is converted to a reactive
      nitrene, transforming transient bindings of interacting structures to covalent
      bonds. In contrast to the sulfo-N-hydroxysuccinimide (sulfo-NHS) moiety of sulfo
      SBED, which attaches quite unspecifically to amino groups, cBED includes a
      cadaverine moiety that can be attached by transglutaminase more specifically to
      certain glutamine residues. For instance, thymosin beta4 can be labeled with cBED
      using tissue transglutaminase. By high-resolution HPLC/ESI-MS (electrospray
      ionization-mass spectrometry) and tandem MS (MS/MS) of the trypsin digest, it was
      established that glutamine residues at positions 23 and 36 were labeled, whereas
      Q39 showed no reactivity. The covalent binding of cBED to thymosin beta4 did not
      influence its G-actin sequestering activity, and the complex could be used to
      identify new interaction partners. Therefore, cBED can be used to better
      understand the multifunctional role of thymosin beta4 as well as of other
      proteins and peptides.

PMID- 24732117
TI  - The toenail: the distal end of human oxygenation.

PMID- 24732122
TI  - Is the 2014 Office of Inspector General Work Plan keeping you up at night?
AB  - Wound care providers should do everything possible to prevent becoming a target
      for OIG investigations, which will surely keep them up at night. The best way to
      get a good night's sleep is to follow the most current coding, payment, coverage,
      and documentation regulations that pertain to your business. Then, consider the
      focus areas of the annual OIG Work Plan as " a heads-up." If you wish to read the
      entire 2014 OIG Work Plan, you can find it at http://www.oig.hhs.gov.

PMID- 24732116
TI  - A novel berbamine derivative inhibits cell viability and induces apoptosis in
      cancer stem-like cells of human glioblastoma, via up-regulation of miRNA-4284 and
      JNK/AP-1 signaling.
AB  - Glioblastoma (GBM) is the most common primary brain tumor, accounting for
      approximately 40% of all central nervous system malignancies. Despite standard
      treatment consisting of surgical resection, radiotherapy and/or chemotherapy, the
      prognosis for GBM is poor; with a median survival of 14.6 months. The cancer stem
      cell or cancer-initiating cell model has provided a new paradigm for
      understanding development and recurrence of GBM following treatment. Berbamine
      (BBM) is a natural compound derived from the Berberis amurensis plant, and along
      with its derivatives, has been shown to exhibit antitumor activity in several
      cancers. Here, we reported that a novel synthetic Berbamine derivative, BBMD3,
      inhibits cell viability and induces apoptosis of cancer stem-like cells (CSCs) in
      a time- and dose-dependent manner when the CSCs from four GBM patients (PBT003,
      PBT008, PBT022, and PBT030) were cultured. These CSCs grew in neurospheres and
      expressed CD133 and nestin as markers. Treatment with BBMD3 destroyed the
      neurosphere morphology, and led to the induction of apoptosis in the CSCs.
      Induction of apoptosis in these CSCs is dependent upon activation of caspase-3
      and cleavage of poly (ADP-ribose) polymerase (PARP). MicroRNA-4284 (miR-4284) was
      shown to be over-expressed about 4-fold in the CSCs following BBMD3 treatment.
      Furthermore, transfection of synthetic anti-sense oligonucleotide against human
      miR-4284 partially blocked the anticancer effects of BBMD3 on the GBM derived
      CSCs. BBMD3 also increased phosphorylation of the c-Jun N-terminal kinase
      (JNK)/stress-activated protein kinase (SAPK), resulting in an increase expression
      of phosphorylated c-Jun and total c-Fos; the major components of transcriptional
      factor AP-1. The JNK-c-Jun/AP-1 signaling pathway plays an important role in the
      induction of apoptosis in response to UV irradiation and some drug treatments.
      Targeting glioblastoma stem-like cells with BBMD3 is therefore novel, and may
      have promise as an effective therapeutic strategy for treating GBM patients. 

PMID- 24732123
TI  - The management of intractable pain with adjuvant pulsed electromagnetic field
      therapy.
AB  - This case describes a 51-year-old woman who reported experiencing severe,
      constant pain, diffusely located in the region of her right mandible neck
      (primarily involving the mandible, lower right molars, the neck, the upper back,
      and the shoulder) during the course of several years. Surgical interventions
      (root canal, spinal fusion) were performed to address potential sources of pain.
      Despite these interventions, the patient reported severe pain after both
      surgeries, which persisted beyond the acute postoperative period. Additional
      pharmacological interventions and physical therapy were also attempted;
      nonetheless, the patient reported that pain remained severe and constant for
      approximately 2 years. On the basis of the patient's poor response to
      conventional treatments, a novel approach of botulinum toxin (BTX) injections was
      initiated. When pulsed electromagnetic field therapy was added, the need for BTX
      injections decreased, with the patient reporting a noticeable decrease in pain
      intensity and an improvement in quality of life measures. Currently, the patient
      continues to use pulsed electromagnetic field therapy regularly for pain
      management, which has allowed her to reduce the use of other interventions and
      avoid continued use of narcotic medications. Considering the need for
      multifaceted pain management approaches in the treatment of chronic pain, this
      case is relevant for wound care practitioners attending to patients with chronic
      postincisional wound pain because the outcome highlights the utility of a
      nonpharmacological, complementary pain management intervention for closed, yet
      persistently painful, postoperative wounds. 

PMID- 24732124
TI  - Clinical evaluation comparing the efficacy of aquacel Ag with vaseline gauze
      versus 1% silver sulfadiazine cream in toxic epidermal necrolysis.
AB  - OBJECTIVE: The purpose of this study was to determine whether using Aquacel Ag
      (ConvaTec, Skillman, New Jersey) with Vaseline (Unilever, London, England) gauze
      instead of silver sulfadiazine cream (SSD) as the wound care protocol to treat
      toxic epidermal necrolysis (TEN) can improve wound healing, pain control, and
      reduction of labor costs. DESIGN: A retrospective chart review. SETTING: A burn
      center with 2 plastic surgeons and 11 nursing staff. PATIENTS: A pathologist
      diagnosed TEN in 35 patients admitted to the burn center from 1995 to 2009. MAIN
      OUTCOME MEASURES: Parameters included the patient's profile, dressing choice,
      severity-of-illness score for TEN, time to 95% re-epithelialization, visual
      analog scale pain scores before second dressing change, and labor cost. The
      exclusion criterion was wound care with neither Aquacel Ag with Vaseline nor SSD
      exclusively. RESULTS: Twenty patients were enrolled in this study. In the group
      using Aquacel Ag with Vaseline gauze, the visual analog scale score was
      significantly less than that of the SSD group (P = .02). Labor costs were
      significantly lower in the Aquacel Ag with Vaseline gauze group (P < .01).
      Commencement of specific dressing to 95% re-epithelialization (P = .09) and time
      spent in the second dressing change (P = .05) had no statistical significance
      between the 2 groups. CONCLUSIONS: This study showed that Aquacel Ag with
      Vaseline gauze decreased pain and labor costs but did not shorten wound healing
      time. Thus, Aquacel Ag with Vaseline gauze can be an efficient method for
      treating TEN wounds.

PMID- 24732125
TI  - Effects of paroxetine on cutaneous wound healing in healthy and diabetic rats.
AB  - OBJECTIVE: The aim of this study was to evaluate the histologic effects of acute
      paroxetine administration on wound healing in healthy and streptozotocin-induced
      diabetic rats. DESIGN: This study has a randomized controlled experimental
      design. SETTING: Healthy (n = 32) and diabetic (n = 32) rats were further divided
      into 2 groups of saline or paroxetine administration. PARTICIPANTS: Sixty-four
      male Sprague-Dawley rats were used in this study. INTERVENTIONS: Paroxetine was
      injected intraperitoneally every day. Full-thickness excision wounds were created
      with a 4-mm dermal punch on the back of all rats. The healing wound area was
      removed with a 6-mm dermal punch at postwounding days 1, 3, 7, and 14. MAIN
      OUTCOME MEASURES: Polymorphonuclear leukocyte, mononuclear inflammatory cell,
      fibroblast, and blood vessel counts and epithelialization were evaluated under
      light microscope. MAIN RESULTS: There was no statistically significant difference
      observed in the polymorphonuclear leukocyte, mononuclear inflammatory cell, and
      blood vessel counts in the healthy and diabetic rats with and without paroxetine
      administration. The number of fibroblasts was significantly higher at
      postwounding day 14 of the paroxetine-administered healthy rats compared with the
      saline-administered healthy rats (P = .04). However, the number of fibroblasts
      did not show any difference by paroxetine administration in the diabetic rats.
      There was no statistically significant difference in epithelialization regarding
      all the postwounding days, but complete epithelialization was observed in all
      rats on postwounding day 14 in the healthy and paroxetine-administered group.
      CONCLUSION: Short-term paroxetine administration may enhance cutaneous wound
      healing by increasing the number of fibroblasts and causing better
      epithelialization over time in healthy rats but not in diabetic rats.

PMID- 24732126
TI  - Clinical and microbiologic evaluation of chronic leg ulcers: a cross-sectional
      study.
AB  - OBJECTIVE: This study aimed at evaluating the flora and bacterial load of chronic
      leg ulcers (CLUs) according to the clinical judgment of colonization or
      infection. DESIGN: This was an analytical and cross-sectional study. SETTING:
      This study was conducted in an outpatient wound care unit in the Dermatology
      Department of the Botucatu School of Medicine-UNESP, Brazil. PARTICIPANTS: The
      participants were patients with CLUs who did not use systemic antibiotics.
      METHODS: The ulcers were clinically divided into 3 groups: ulcers with good
      granulation tissue (GGT), critical colonization (CC), and infection. Secretion
      was collected from a 1-cm area using a swab and seeded by the semiquantitative
      method. OUTCOME MEASURES: The main outcome measures were genus and species of the
      bacteria found in the cultures and result of the semiquantitative culture
      correlating with the clinical diagnosis of GGT, CC, and infection. MAIN RESULTS:
      Seventy-seven ulcers were evaluated: 27 with GGT, 29 with CC, and 21 with
      infection. Gram-negative bacteria were most often found in all groups (81%):
      Pseudomonas aeruginosa, in granulation and colonized ulcers, and Proteus
      mirabilis, in infected ulcers. Ulcers from the infected group showed higher
      bacterial load. CONCLUSIONS: The flora of CLUs was predominantly constituted by
      gram-negative bacteria, and P aeruginosa was the most prevalent. The bacterial
      load of infected ulcers was higher as compared with the others, although some
      ulcers with GGT also presented a high load. The interpretation of microbiologic
      tests based on the swab techniques and even on semiquantitative analysis requires
      close clinical correlation.

PMID- 24732127
TI  - Influence of smoking on wound healing in patients undergoing nail matrix
      phenolization: a prospective randomized clinical study.
AB  - PURPOSE: To enhance the learner's competence with knowledge of the effect of
      smoking on wound healing in patients undergoing nail matrix phenolization. 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.
      Summarize factors that affect wound cicatrization and pathophysiologic mechanisms
      of impaired healing from smoking as found in prior studies from review of the
      literature.2. Analyze components and findings of this research study on how
      healing from phenol ablation is influenced by smoking. ABSTRACT OBJECTIVE:
      Healing time can be delayed by extrinsic factors such as smoking. No controlled
      study has analyzed the influence of smoking on wound healing in patients
      undergoing nail matrix phenolization. The main objective of this work was to
      analyze wound healing burns after segmental phenolization in smoker versus
      nonsmoker patients; the secondary aim was to examine the influence of curettage
      in both groups. DESIGN: In a prospective clinical study, 90 podiatric patients
      (53 smokers and 37 nonsmokers) with onychocryptosis were randomized to 1 of 2
      treatment arms: phenolization with curettage and phenolization alone. The primary
      outcome was to analyze the healing time (in days) after the segmental
      phenolization in both groups. Healing was monitored for spontaneous wound closure
      by clinical assessments and by digital photographs. MAIN RESULTS: The healing
      time in the curettage group was (8.80 +/- 1.51 days in smokers vs 6.72 +/- 1.26
      days in nonsmokers; P < .0001) and (13.24 +/- 1.8 days in the smoker group vs
      10.67 +/- 1.78 days in the nonsmoker group; P < .0001) in the phenolization alone
      group. Significant differences were found in respect to time to healing among
      smokers in both groups (13.24 +/- 1.8 days in the phenolization group vs 8.80 +/-
      1.51 days in the curettage group; P < .0001). Similarly, significant differences
      were found with respect to time to healing among nonsmokers in both groups (10.46
      +/- 2.04 days in the phenolization group vs 6.71 +/- 1.11 days in the curettage
      group; P = .0001). CONCLUSION: Burn wounds of smokers take longer to heal than
      those of nonsmokers. Curettage of the cauterized tissue reduces healing time and
      should be systematically considered.

PMID- 24732129
TI  - Clinical quality measures and meaningful use.

PMID- 24732130
TI  - Loss of lamin B1 results in prolongation of S phase and decondensation of
      chromosome territories.
AB  - Nuclear lamin B1 (LMNB1) constitutes one of the major structural proteins in the
      lamina mesh. We silenced the expression of LMNB1 by RNA interference in the colon
      cancer cell line DLD-1 and showed a dramatic redistribution of H3K27me3 from the
      periphery to a more homogeneous nuclear dispersion. In addition, we observed
      telomere attrition and an increased frequency of micronuclei and nuclear blebs.
      By 3D-FISH analyses, we demonstrated that the volume and surface of chromosome
      territories were significantly larger in LMNB1-depleted cells, suggesting that
      LMNB1 is required to maintain chromatin condensation in interphase nuclei. These
      changes led to a prolonged S phase due to activation of Chk1. Finally, silencing
      of LMNB1 resulted in extensive changes in alternative splicing of multiple genes
      and in a higher number of enlarged nuclear speckles. Taken together, our results
      suggest a mechanistic role of the nuclear lamina in the organization of
      chromosome territories, maintenance of genome integrity and proper gene splicing.

PMID- 24732131
TI  - Role of protein kinase R in the killing of Leishmania major by macrophages in
      response to neutrophil elastase and TLR4 via TNFalpha and IFNbeta.
AB  - In cutaneous leishmaniasis, Leishmania amazonensis activates macrophage double
      stranded, RNA-activated protein kinase R (PKR) to promote parasite growth. In our
      study, Leishmania major grew normally in RAW cells, RAW-expressing dominant
      negative PKR (PKR-DN) cells, and macrophages of PKR-knockout mice, revealing that
      PKR is dispensable for L. major growth in macrophages. PKR activation in infected
      macrophages with poly I:C resulted in parasite death. Fifty percent of L. major
      knockout lines for the ecotin-like serine peptidase inhibitor (ISP2;
      Deltaisp2/isp3), an inhibitor of neutrophil elastase (NE), died in RAW cells or
      macrophages from 129Sv mice, as a result of PKR activation. Inhibition of PKR or
      NE or neutralization of Toll-like receptor 4 or 2(TLR4 or TLR2) prevented the
      death of Deltaisp2/isp3. Deltaisp2/isp3 grew normally in RAW-PKR-DN cells or
      macrophages from 129Sv pkr(-/-), tlr2(-/-), trif(-/-), and myd88(-/-) mice,
      associating NE activity, PKR, and TLR responses with parasite death.
      Deltaisp2/isp3 increased the expression of mRNA for TNF-alpha by 2-fold and of
      interferon beta (IFNbeta) in a PKR-dependent manner. Antibodies to TNF-alpha
      reversed the 95% killing by Deltaisp2/isp3, whereas they grew normally in
      macrophages from IFN receptor-knockout mice. We propose that ISP2 prevents the
      activation of PKR via an NE-TLR4-TLR2 axis to control innate responses that
      contribute to the killing of L. major.-Faria, M. S., Calegari-Silva, T. C., de
      Carvalho Vivarini, A., Mottram, J. C., Lopes, U. G., Lima, A. P. C. A. Role of
      protein kinase R in the killing of Leishmania major by macrophages in response to
      neutrophil elastase and TLR4 via TNFalpha and IFNbeta. 

PMID- 24732133
TI  - Compensatory regulation of HDAC5 in muscle maintains metabolic adaptive responses
      and metabolism in response to energetic stress.
AB  - Some gene deletions or mutations have little effect on metabolism and metabolic
      adaptation because of redundancy and/or compensation in metabolic pathways. The
      mechanisms for redundancy and/or compensation in metabolic adaptation in
      mammalian cells are unidentified. Here, we show that in mouse muscle and myogenic
      cells, compensatory regulation of the histone deacetylase (HDAC5) transcriptional
      repressor maintains metabolic integrity. HDAC5 phosphorylation regulated the
      expression of diverse metabolic genes and glucose metabolism in mouse C2C12
      myogenic cells. However, loss of AMP-activated protein kinase (AMPK), a HDAC5
      kinase, in muscle did not affect HDAC5 phosphorylation in mouse skeletal muscle
      during exercise, but resulted in a compensatory increase (32.6%) in the
      activation of protein kinase D (PKD), an alternate HDAC5 kinase. Constitutive PKD
      activation in mouse C2C12 myogenic cells regulated metabolic genes and glucose
      metabolism. Although aspects of this response were HDAC5 phosphorylation
      dependent, blocking HDAC5 phosphorylation when PKD was active engaged an
      alternative compensatory adaptive mechanism, which involved post-transcriptional
      reductions in HDAC5 mRNA (-93.1%) and protein. This enhanced the expression of a
      specific subset of metabolic genes and mitochondrial metabolism. These data show
      that compensatory regulation of HDAC5 maintains metabolic integrity in mammalian
      cells and reinforces the importance of preserving the cellular metabolic adaptive
      response.

PMID- 24732134
TI  - Dengue NS1 and prM antibodies increase the sensitivity of acute dengue diagnosis
      test and differentiate from Japanese encephalitis infection.
AB  - Accurate and early diagnosis of dengue infection is essential for dengue case
      management. In outbreak conditions, it is essential to include two different
      tests to diagnose dengue and the choice depends on the number of days after the
      onset of illness in which the sample is collected. During the laboratory
      diagnosis of dengue in late acute and convalescent phase by MAC-ELISA, it is
      necessary to rule out possible cross reactions of closely related flavivirus,
      such as Japanese encephalitis virus which is commonly co-circulating. In the
      present investigation, the usefulness of dengue virus NS1 and prM antibodies in
      diagnosing and differentiating dengue from Japanese encephalitis infection was
      assessed using samples collected during out-breaks. It was shown here that,
      detection of antibodies against dengue NS1 and prM proteins increases the
      sensitivity of dengue diagnosis until 15days. Moreover, detection of antibodies
      against both proteins was able to differentiate dengue from Japanese encephalitis
      infection. 

PMID- 24732132
TI  - Clinical and biochemical profiles suggest fibromuscular dysplasia is a systemic
      disease with altered TGF-beta expression and connective tissue features.
AB  - Fibromuscular dysplasia (FMD) is a rare, nonatherosclerotic arterial disease for
      which the molecular basis is unknown. We comprehensively studied 47 subjects with
      FMD, including physical examination, spine magnetic resonance imaging, bone
      densitometry, and brain magnetic resonance angiography. Inflammatory biomarkers
      in plasma and transforming growth factor beta (TGF-beta) cytokines in patient
      derived dermal fibroblasts were measured by ELISA. Arterial pathology other than
      medial fibrodysplasia with multifocal stenosis included cerebral aneurysm, found
      in 12.8% of subjects. Extra-arterial pathology included low bone density
      (P<0.001); early onset degenerative spine disease (95.7%); increased incidence of
      Chiari I malformation (6.4%) and dural ectasia (42.6%); and physical examination
      findings of a mild connective tissue dysplasia (95.7%). Screening for mutations
      causing known genetically mediated arteriopathies was unrevealing. We found
      elevated plasma TGF-beta1 (P=0.009), TGF-beta2 (P=0.004) and additional
      inflammatory markers, and increased TGF-beta1 (P=0.0009) and TGF-beta2 (P=0.0001)
      secretion in dermal fibroblast cell lines from subjects with FMD compared to age-
      and gender-matched controls. Detailed phenotyping of patients with FMD allowed us
      to demonstrate that FMD is a systemic disease with alterations in common with the
      spectrum of genetic syndromes that involve altered TGF-beta signaling and offers
      TGF-beta as a marker of FMD.

PMID- 24732136
TI  - Cell death stages in single apoptotic and necrotic cells monitored by Raman
      microspectroscopy.
AB  - Although apoptosis and necrosis have distinct features, the identification and
      discrimination of apoptotic and necrotic cell death in vitro is challenging.
      Immunocytological and biochemical assays represent the current gold standard for
      monitoring cell death pathways; however, these standard assays are invasive,
      render large numbers of cells and impede continuous monitoring experiments. In
      this study, both room temperature (RT)-induced apoptosis and heat-triggered
      necrosis were analyzed in individual Saos-2 and SW-1353 cells by utilizing Raman
      microspectroscopy. A targeted analysis of defined cell death modalities,
      including early and late apoptosis as well as necrosis, was facilitated based on
      the combination of Raman spectroscopy with fluorescence microscopy. Spectral
      shifts were identified in the two cell lines that reflect biochemical changes
      specific for either RT-induced apoptosis or heat-mediated necrosis. A supervised
      classification model specified apoptotic and necrotic cell death based on single
      cell Raman spectra. To conclude, Raman spectroscopy allows a non-invasive,
      continuous monitoring of cell death, which may help shedding new light on complex
      pathophysiological or drug-induced cell death processes. 

PMID- 24732135
TI  - DeltaNp63 isoform-mediated beta-defensin family up-regulation is associated with
      (lymph)angiogenesis and poor prognosis in patients with squamous cell carcinoma.
AB  - Beside a role in normal development/differentiation, high p63 immunoreactivity is
      also frequently observed in squamous cell carcinoma (SCC). Due to the complexity
      of the gene, the role of each p63 isotype in tumorigenesis is still confusing.
      Constitutively produced or induced in inflammatory conditions, human beta
      defensins (HbetaDs) are cationic peptides involved in host defenses against
      bacteria, viruses and fungi. Here, we investigated both the role of p63 proteins
      in the regulation of HbetaDs and the implication of these antimicrobial peptides
      in tumor (lymph)angiogenesis. Thus, in contrast to TAp63 isotypes, we observed
      that DeltaNp63 proteins (alpha, beta, gamma) induce HbetaD1, 2 and 4 expression.
      Similar results were observed in cancer tissues and cell lines. We next
      demonstrated that DeltaNp63-overexpressing SCC are associated with both a poor
      prognosis and a high tumor vascularisation and lymphangiogenesis. Moreover, we
      showed that HbetaDs exert a chemotactic activity for (lymphatic) endothelial
      cells in a CCR6-dependent manner. The ability of HbetaDs to enhance
      (lymph)angiogenesis in vivo was also evaluated. We observed that HbetaDs increase
      the vessel number and induce a significant increase in relative vascular area
      compared to negative control. Taken together, the results of this study suggest
      that DeltaNp63-regulated HbetaD could promote tumor (lymph)angiogenesis in SCC
      microenvironment. 

PMID- 24732137
TI  - Quantitative analysis of abdominal aortic calcification in CKD patients without
      dialysis therapy by use of the Agatston score.
AB  - BACKGROUND/AIM: The aim of the present study was to quantitatively examine
      factors associated with aortic calcification in non-dialysis CKD patients.
      METHODS: We quantitatively investigated aortic calcification from the renal
      artery to the bifurcation in 149 non-dialysis CKD patients (58+/-16 years; 96
      males and 53 females, 48 diabetics; eGFR 40.3 +/- 29.3 ml/min), and measured
      Agatston scores using multi-slice computed tomography. RESULT: Of 149 patients,
      aortic calcification was present in 117. In patients with aortic calcification,
      age (p<0.001), C-reactive protein (p<0.001), and intact-PTH (p < 0.001) were
      significantly higher, estimated glomerular filtration rate (eGFR) was
      significantly lower (p<0.001), and diabetes was observed more often (p<0.05). In
      regards to the degree of aortic calcification, the Agatston scores correlated
      significantly and positively with age (rho=0.438, p<0.001) and serum phosphate
      (rho=0.208, p=0.024), and correlated significantly but negatively with e-GFR
      (rho=-0.353, p<0.001). In multiple regression analysis, eGFR was associated
      significantly and independently with the log [Agatston score] (beta=-0.346,
      p<0.01), after adjustment for several confounders including serum phosphate and
      the presence of diabetes. CONCLUSIONS: Hyperphospatemia, chronic inflammation,
      diabetes, and decreased GFR are associated significantly with the presence of
      aortic calcification in non-dialysis CKD patients. Decreased eGFR was associated
      significantly and independently with the quantitative degree of aortic
      calcification.

PMID- 24732138
TI  - Framing the future's expert panel report on the MPH degree: a step backward?
AB  - Framing the Future Task Force, a group assembled by the Association of Schools
      and Programs of Public Health to identify key issues facing public health
      education as it enters its second 100 years, has recently released a report, "A
      Master of Public Health Degree for the 21st Century." The report calls for a
      significant shift in emphasis for the MPH degree away from a generalist, core
      curriculum in favor of a greater emphasis on areas of specialty. This commentary
      argues that such a shift would reverse the progress made since the 1988 Institute
      of Medicine report called on academia to better meet practice needs. Rather, the
      MPH of the 21st century should continue to focus on methods to better teach core
      competencies in public health practice at an advanced level.

PMID- 24732139
TI  - Estimated glomerular filtration rate decline as a predictor of dialysis in kidney
      transplant recipients.
AB  - BACKGROUND: It is now common for individuals to require dialysis following the
      failure of a kidney transplant. Management of complications and preparation for
      dialysis are suboptimal in this group. To aid planning, it is desirable to
      estimate the time to dialysis requirement. The rate of decline in the estimated
      glomerular filtration rate (eGFR) may be used to this end. METHODS: This study
      compared the rate of eGFR decline prior to dialysis commencement between
      individuals with failing transplants and transplant-naive patients. The rate of
      eGFR decline was also compared between transplant recipients with and without
      graft failure. eGFR was calculated using the four-variable MDRD equation with
      rate of decline calculated by least squares linear regression. RESULTS: The
      annual rate of eGFR decline in incident dialysis patients with graft failure
      exceeded that of the transplant-naive incident dialysis patients. In the
      transplant cohort, the mean annual rate of eGFR decline prior to graft failure
      was 7.3 ml/min/1.73 m(2) compared to 4.8 ml/min/1.73 m(2) in the transplant-naive
      group (p < 0.001) and 0.35 ml/min/1.73 m(2) in recipients without graft failure
      (p < 0.001). Factors associated with eGFR decline were recipient age, decade of
      transplantation, HLA mismatch and histological evidence of chronic immunological
      injury. CONCLUSIONS: Individuals with graft failure have a rapid decline in eGFR
      prior to dialysis commencement. To improve outcomes, dialysis planning and
      management of chronic kidney disease complications should be initiated earlier
      than in the transplant-naive population.

PMID- 24732140
TI  - Treating gestational diabetes reduces perinatal morbidity.

PMID- 24732141
TI  - Impact of etiology on the outcomes in heart failure patients treated with cardiac
      resynchronization therapy: a meta-analysis.
AB  - BACKGROUND: Cardiac resynchronization therapy (CRT) has been extensively
      demonstrated to benefit heart failure patients, but the role of underlying heart
      failure etiology in the outcomes was not consistently proven. This meta-analysis
      aimed to determine whether efficacy and effectiveness of CRT is affected by
      underlying heart failure etiology. METHODS AND RESULTS: Searches of MEDLINE,
      EMBASE and Cochrane databases were conducted to identify RCTs and observational
      studies that reported clinical and functional outcomes of CRT in ischemic
      cardiomyopathy (ICM) and non-ischemic cardiomyopathy (NICM) patients. Efficacy of
      CRT was assessed in 7 randomized controlled trials (RCTs) with 7072 patients and
      effectiveness of CRT was evaluated in 14 observational studies with 3463 patients
      In the pooled analysis of RCTs, we found that CRT decreased mortality or heart
      failure hospitalization by 29% in ICM patients (95% confidence interval [CI], 21%
      to 35%), and by 28% (95% CI, 18% to 37%) in NICM patients. No significant
      difference was observed between the 2 etiology groups (P = 0.55). In the pooled
      analysis of observational studies, however, we found that ICM patients had a 54%
      greater risk for mortality or HF hospitalization than NICM patients (relative
      risk: 1.54; 95% CI: 1.30-1.83; P<0.001). Both RCTs and observational studies
      demonstrated that NICM patients had greater echocardiographic improvements in the
      left ventricular ejection fraction and end-systolic volume, as compared with ICM
      patients (both P<0.001). CONCLUSION: CRT might reduce mortality or heart failure
      hospitalization in both ICM and NICM patients similarly. The improvement of the
      left ventricular function and remodeling is greater in NICM patients.

PMID- 24732142
TI  - Regional-specific effects of ovarian hormone loss on synaptic plasticity in adult
      human APOE targeted replacement mice.
AB  - The human apolipoprotein epsilon4 allele (APOE4) has been implicated as one of
      the strongest genetic risk factors associated with Alzheimer's disease (AD) and
      in influencing normal cognitive functioning. Previous studies have demonstrated
      that mice expressing human apoE4 display deficits in behavioral and
      neurophysiological outcomes compared to those with apoE3. Ovarian hormones have
      also been shown to be important in modulating synaptic processes underlying
      cognitive function, yet little is known about how their effects are influenced by
      apoE. In the current study, female adult human APOE targeted replacement (TR)
      mice were utilized to examine the effects of human APOE genotype and long-term
      ovarian hormone loss on synaptic plasticity in limbic regions by measuring
      dendritic spine density and electrophysiological function. No significant
      genotype differences were observed on any outcomes within intact mice. However,
      there was a significant main effect of genotype on total spine density in apical
      dendrites in the hippocampus, with post-hoc t-tests revealing a significant
      reduction in spine density in apoE3 ovariectomized (OVX) mice compared to sham
      operated mice. There was also a significant main effect of OVX on the magnitude
      of LTP, with post-hoc t-tests revealing a decrease in apoE3 OVX mice relative to
      sham. In contrast, apoE4 OVX mice showed increased synaptic activity relative to
      sham. In the lateral amygdala, there was a significant increase in total spine
      density in apoE4 OVX mice relative to sham. This increase in spine density was
      consistent with a significant increase in spontaneous excitatory activity in
      apoE4 OVX mice. These findings suggest that ovarian hormones differentially
      modulate synaptic integrity in an apoE-dependent manner within brain regions that
      are susceptible to neurophysiological dysfunction associated with AD. 

PMID- 24732143
TI  - Physical activity, sedentary time and gain in overall and central body fat: 7
      year follow-up of the ProActive trial cohort.
AB  - OBJECTIVE: The objective of this study is to examine the independent associations
      of time spent in moderate-to-vigorous physical activity (MVPA) and sedentary (SED
      time), with total and abdominal body fat (BF), and the bidirectionality of these
      associations in adults at high risk of type 2 diabetes. DESIGN AND SUBJECTS: We
      measured MVPA (min per day) and SED-time (h per day) by accelerometry, and
      indices of total (body weight, fat mass (FM), BF% and FM index) and abdominal BF
      (waist circumference (WC)) using standard procedures in 231 adults (41.3 +/- 6.4
      years) with parental history of type 2 diabetes (ProActive UK) at baseline, 1
      year and 7-year follow-up. Mixed effects models were used to quantify the
      independent associations (expressed as standardised beta-coefficients (95%
      confidence interval (CI))) of MVPA and SED-time with fat indices, using data from
      all three time points. All models were adjusted for age, sex, intervention arm,
      monitor wear time, follow-up time, smoking status, socioeconomic status and
      MVPA/SED-time. RESULTS: MVPA was inversely and independently associated with all
      indices of total BF (for example, 1 s.d. higher MVPA was associated with a
      reduction in FM, beta = -0.09 (95% CI: -0.14, -0.04) s.d.) and abdominal BF (for
      example, WC: beta = -0.07 (-0.12, -0.02)). Similarly, higher fat indices were
      independently associated with a reduction in MVPA (for example, WC: beta = -0.25
      (-0.36, -0.15); FM: beta = -0.27 (-0.36, -0.18)). SED-time was positively and
      independently associated with most fat indices (for example, WC: beta = 0.03 (
      0.04, 0.09); FM: beta = 0.10 (0.03, 0.17)). Higher values of all fat indices
      independently predicted longer SED-time (for example, WC: beta = 0.10 (0.02,
      0.18), FM: beta = 0.15 (0.07, 0.22)). CONCLUSIONS: The associations of MVPA and
      SED-time with total and abdominal BF are bidirectional and independent among
      individuals at high risk for type 2 diabetes. The association between BF and MVPA
      is stronger than the reciprocal association, highlighting the importance of
      considering BF as a determinant of decreasing activity and a potential
      consequence. Promoting more MVPA and less SED-time may reduce total and abdominal
      BF.

PMID- 24732144
TI  - CREB/TRH pathway in the central nervous system regulates energy expenditure in
      response to deprivation of an essential amino acid.
AB  - BACKGROUND: In the central nervous system (CNS), thyrotropin-releasing hormone
      (TRH) has an important role in regulating energy balance. We previously showed
      that dietary deprivation of leucine in mice increases energy expenditure through
      CNS-dependent regulation. However, the involvement of central TRH in this
      regulation has not been reported. METHODS: Male C57J/B6 mice were maintained on a
      control or leucine-deficient diet for 7 days. Leucine-deprived mice were either
      third intracerebroventricular (i.c.v.) injected with a TRH antibody followed by
      intraperitoneal (i.p.) injection of triiodothyronine (T3) or i.c.v. administrated
      with an adenovirus of shCREB (cAMP-response element binding protein) followed by
      i.c.v. injection of TRH. Food intake and body weight were monitored daily. Oxygen
      consumption, physical activity and rectal temperature were assessed after the
      treatment. After being killed, the hypothalamus and the brown adipose tissue were
      collected and the expression of related genes and proteins related was analyzed.
      In other experiments, control or leucine-deficient medium incubated primary
      cultured neurons were either infected with adenovirus-mediated short hairpin RNA
      targeting extracellular signal-regulated kinases 1 and 2 (Ad-shERK1/2) or
      transfected with plasmid-overexpressing protein phosphatase 1 regulatory subunit
      3C (PPP1R3C). RESULTS: I.c.v. administration of anti-TRH antibodies significantly
      reduced leucine deprivation-stimulated energy expenditure. Furthermore, the
      effects of i.c.v. TRH antibodies were reversed by i.p. injection of T3 during
      leucine deprivation. Moreover, i.c.v. injection of Ad-shCREB (adenovirus-mediated
      short hairpin RNA targeting CREB) significantly suppressed leucine deprivation
      stimulated energy expenditure via modulation of TRH expression. Lastly, TRH
      expression was regulated by CREB, which was phosphorylated by ERK1/2 and
      dephosphorylated by PPP1R3C-containing protein Ser/Thr phosphatase type 1 (PP1)
      under leucine deprivation in vitro. CONCLUSIONS: Our data indicate a novel role
      for TRH in regulating energy expenditure via T3 during leucine deprivation.
      Furthermore, our findings reveal that TRH expression is activated by CREB, which
      is phosphorylated by ERK1/2 and dephosphorylated by PPP1R3C-containing PP1.
      Collectively, our studies provide novel insights into the regulation of energy
      homeostasis by the CNS in response to an essential amino-acid deprivation.

PMID- 24732145
TI  - 'Obesity paradox' misunderstands the biology of optimal weight throughout the
      life cycle.
AB  - The 'obesity paradox' refers to observations that run counter to the thesis that
      normal weight (BMI 18.5-24.9 g/m(2)) provides the lowest mortality and higher
      weight is associated with greater mortality. We argue that the weight of lowest
      mortality is influenced by aging and chronic disease, with mortality advantage
      extending into the overweight and even class I obese ranges under some
      circumstances. A focus on quality nutrition, physical activity, fitness, and
      maintaining function in these weight ranges may be preferable to a focus on
      intentional weight loss, which has uncertain effects. The 'obesity paradox' is no
      'paradox' if one defines and interprets 'ideal' weight appropriately.

PMID- 24732147
TI  - Obesity Paradox should not interfere with public health efforts.
AB  - The Obesity Paradox could result in confusing messages that derail beneficial
      environmental changes and lead to reduced efforts by physicians to provide
      healthy lifestyle treatment plans to their obese patients. The Obesity Paradox
      applies in the main to individuals who have a disease, and therefore observed
      associations with mortality illustrating the Paradox may be more susceptible to
      certain types of bias than would be found in healthy individuals. Although
      individualization of weight loss advice for patients with serious disease is
      appropriate in medical settings, this does not supplant the need for general
      efforts to prevent and treat obesity. 

PMID- 24732146
TI  - A multi-level analysis showing associations between school neighborhood and child
      body mass index.
AB  - OBJECTIVE: The objective of this study is to examine associations between aspects
      of the environment in school neighborhoods and childhood body mass index
      percentile (BMIp). METHODS: Trained medical students visited 46 elementary
      schools in the Kansas City metropolitan area to conduct medical screenings that
      included the height and weight measurements of 12 118 boys and girls 4-12 years
      of age in the academic year 2008-2009. For the same time period, aspects of the
      built environment in a 2-mile radius around each school was obtained from the
      Walkscore database. Other environmental characteristics (for example, population
      change) of these areas were also obtained from various sources. Hierarchical
      linear modeling was used to estimate the associations between neighborhood- and
      individual-level factors and BMIp. RESULTS: Population size along with the number
      of fast-food restaurants and grocery stores were positively associated with BMIp,
      whereas population change along with the number of parks and fitness centers were
      inversely associated with BMIp. CONCLUSIONS: After considering individual-level
      factors and the random effects of schools, environmental elements of school
      neighborhoods predict childhood BMIp. This study offers evidence of the health
      influence of school neighborhoods in a way that can inform neighborhood
      redevelopment efforts.

PMID- 24732148
TI  - HPLC/ESI-MS(n) method for non-amino bisphosphonates: application to the detection
      of tiludronate in equine plasma.
AB  - Tiludronate is a non-nitrogen-containing biphosphonate drug approved in equine
      veterinary medicine for the treatment of navicular disease and bone sparvin in
      horse. Its hydrophilic properties and its strong affinity for the bone have made
      the control of its use quite difficult. After an initial step of method
      development in plasma and urine, due to a strong matrix effect and erratic
      detection in urine, the final method development was conducted in plasma. After
      addition of (3-trifluoromethylphenyl) thiomethylene biphosphonic acid as internal
      standard, automated sample preparation consisted of a filtration on a Nexus
      cartridge followed by a Solid Phase Extraction on an Oasis WAX cartridge with
      weak anion exchange properties. After methylation of the residue with trimethyl
      orthoacetate (TMOA), analysis was conducted by HPLC/ESI-MS(n) on a LTQ mass
      spectrometer. The method has been validated with a LOD and LOQ of respectively 1
      and 2.5ng/mL. Using a weighting factor of 1/concentration(2), a linear model was
      suitable in the range of 2.5 up to 500ng/mL. Precision and accuracy data
      determined at two concentrations were satisfactory (i.e. less than 15%).
      Carryover would have been a problem but this has finally been fixed using the
      additional steps of washing during robotised SPE extraction and analysis on both
      the autosampler and the analytical column. The method was successfully employed
      for the first time to the quantification of tiludronate in plasma samples
      collected from horses treated with TildrenTM (Intravenous administration at the
      dose of 0.1mg/kg/day for 10 days). 

PMID- 24732149
TI  - Determination of mesoridazine by liquid chromatography-tandem mass spectrometry
      and its application to pharmacokinetic study in rats.
AB  - The object of the present study was to develop and validate an assay method of
      mesoridazine in rat plasma using liquid chromatography-tandem mass spectrometry
      (LC-MS/MS). Plasma samples from rats were prepared by simple protein
      precipitation and injected onto the LC-MS/MS system for quantification.
      Mesoridazine and chlorpromazine as an internal standard (IS) were separated by a
      reversed phase C18 column. A mobile phase was composed of 10mM ammonium formate
      in water and acetonitrile (ACN) (v/v) by a linear gradient system, increasing the
      percentage of ACN from 2% at 0.4min to 98% at 2.5min with 4min total run time.
      The ion transitions monitored in positive-ion mode [M+H](+) of multiple-reaction
      monitoring (MRM) were m/z 387>126 for mesoridazine and m/z 319>86 for IS. The
      detector response was specific and linear for mesoridazine at concentrations
      within the range 0.001-4MUg/ml and the correlation coefficient (R(2)) was greater
      than 0.999 and the signal-to-noise ratios for the samples were >=10. The intra-
      and inter-day precision and accuracy of the method were determined to be within
      the acceptance criteria for assay validation guidelines. The matrix effects were
      approximately 101 and 99.5% from rat plasma for mesoridazine and chlorpromazine,
      respectively. Mesoridazine was stable under various processing and/or handling
      conditions. Mesoridazine concentrations were readily measured in rat plasma
      samples after intravenous and oral administration. This assay method can be
      practically useful to the pharmacokinetic and/or toxicokinetic studies of
      mesoridazine. 

PMID- 24732150
TI  - Diagnostic performance of standard electrocardiogram for prediction of infarct
      related artery and site of coronary occlusion in unselected STEMI patients
      undergoing primary percutaneous coronary intervention.
AB  - AIMS: To evaluate the relationship between ECG patterns and infarct related
      artery (IRA) in an all-comer population with ST-segment elevation myocardial
      infarction (STEMI) and validate current criteria for identifying IRA (right
      coronary artery (RCA) versus left circumflex artery (LCA)) in inferior STEMI and
      for diagnosing left main (LM) or left anterior descendent artery occlusion (LAD)
      in anterior STEMI. METHODS AND RESULTS: We retrospectively analysed ECGs at
      presentation and coronary angiogram in 885 consecutive patients undergoing
      primary percutaneous coronary intervention. Six ECG patterns were identified:
      anterior-STEMI (n=433; 49.0%), inferior-STEMI (i=365; 43.0%), lateral-STEMI
      (n=43; 5.0%), left bundle branch block (n=26; 3.0%), posterior-STEMI (n=7; 1.0%)
      and de Winter sign (n=7; 1.0%). The last two ECG patterns were univocally
      associated with LCA and proximal LAD occlusion respectively. In patients with
      inferior STEMI, predefined ECG algorithms showed high sensitivity(>90%) for RCA
      occlusion and high specificity(>90%) for LCA. The diagnostic performance was
      mainly determined by RCA dominance. In anterior STEMI the vectorial analysis of
      ST deviation in both frontal and horizontal planes could identify patients with
      LM/proximal LAD occlusion (adjusted-odds ratio for in-hospital mortality =2.45,
      95% confidence interval: 1.31-4.56, p = 0.005) with low sensitivity (maximum 60%;
      using ST-depression in lead II, III, aVF + SigmaSTE aVR + V1-ST depression V6>=0)
      and high specificity (maximum 95%; using ST-depression in inferior leads + ST
      depression in V6). CONCLUSION: In STEMI undergoing primary percutaneous coronary
      intervention, six ECG patterns can be identified with a non-univocal relationship
      to the IRA. In inferior STEMI, vectorial analysis of ST deviation identifies IRA
      with a high appropriateness only when RCA is the dominant artery. In anterior
      STEMI, criteria derived from both frontal and horizontal planes identify
      LM/proximal LAD occlusion with high specificity but low sensitivity.

PMID- 24732151
TI  - Parametric Imaging and Test-Retest Variability of 11C-(+)-PHNO Binding to D2/D3
      Dopamine Receptors in Humans on the High-Resolution Research Tomograph PET
      Scanner.
AB  - (11)C-(+)-4-propyl-9-hydroxynaphthoxazine ((11)C-(+)-PHNO) is an agonist
      radioligand for imaging dopamine D2 and D3 receptors in the human brain with PET.
      In this study we evaluated the reproducibility of (11)C-(+)-PHNO binding
      parameters using a within-day design and assessed parametric imaging methods.
      METHODS: Repeated studies were performed in 8 subjects, with simultaneous
      measurement of the arterial input function and plasma free fraction. Two (11)C
      (+)-PHNO scans for the same subject were separated by 5.4 +/- 0.7 h. After
      compartment models were evaluated, (11)C-(+)-PHNO volumes of distribution (V(T))
      and binding potentials relative to the concentration of tracer in plasma (BP(P)),
      nondisplaceable tracer in tissue (BP(ND)), and free tracer in tissue (BP(F)) were
      quantified using the multilinear analysis MA1 method, with the cerebellum as the
      reference region. Parametric images of BP(ND) were also computed using the
      simplified reference tissue model (SRTM) and SRTM2. RESULTS: The test-retest
      variability of (11)C-(+)-PHNO BP(ND) was 9% in D2-rich regions (caudate and
      putamen). Among D3-rich regions, variability was low in the pallidum (6%) but
      higher in substantia nigra (19%), thalamus (14%), and hypothalamus (21%). No
      significant mass carry-over effect was observed in D3-rich regions, although a
      trend in BP(ND) was present in the substantia nigra (-14% +/- 15%). Because of
      the relatively fast kinetics, low-noise BP(ND) parametric images were obtained
      with both SRTM and SRTM2 without spatial smoothing. CONCLUSION: (11)C-(+)-PHNO
      can be used to compute low-noise parametric images in both D2- and D3-rich
      regions in humans.

PMID- 24732152
TI  - Quantitative Analysis of Amyloid Deposition in Alzheimer Disease Using PET and
      the Radiotracer 11C-AZD2184.
AB  - Characteristic neuropathologic changes in Alzheimer disease (AD) are amyloid-beta
      deposits and neurofibrillary tangles. Recently, a new radioligand for amyloid
      senile plaques, (11)C-labeled 5-(6-{[tert-butyl(dimethyl)silyl]oxy}-1,3
      benzothiazol-2-yl)pyridin-2-amine ((11)C-AZD2184), was developed, and it was
      reported to show rapid brain uptake followed by rapid washout. In this study,
      (11)C-AZD2184 binding in control subjects and AD patients was examined in more
      detail by compartment model analysis using a metabolite-corrected arterial input
      function. The accuracy of simplified quantitative methods using a reference brain
      region was also evaluated. METHODS: After intravenous bolus injection of (11)C
      AZD2184, a dynamic PET scan was obtained for 90 min in 6 control subjects and 8
      AD patients. To obtain the arterial input function, arterial blood sampling and
      high-performance liquid chromatography analysis were performed. RESULTS: Time
      activity curves in all brain regions could be described using the standard 2
      tissue-compartment model. The total distribution volume ratios to reference
      region (DVR) in cerebral cortical regions were significantly higher in AD
      patients than in control subjects. Although there was no conspicuous accumulation
      of radioactivity in white matter as compared with other amyloid radioligands, DVR
      values in the centrum semiovale were more than 1 for both control subjects and AD
      patients, suggesting binding to myelin. The standardized uptake value ratio
      calculated from integrated time-activity curves in brain regions and the
      reference region was statistically in good agreement with DVR. CONCLUSION:
      Although the white matter binding of (11)C-AZD2184 may have some effect on
      cortical measurement, it can be concluded that the kinetic behavior of (11)C
      AZD2184 is suitable for quantitative analysis. The standardized uptake value
      ratio can be used as a validated measure of (11)C-AZD2184 binding in clinical
      examinations without arterial input function.

PMID- 24732153
TI  - Development of a Radiolabeled Irreversible Peptide Ligand for PET Imaging of
      Vascular Endothelial Growth Factor.
AB  - Imaging agents based on peptide probes have desirable pharmacokinetic properties
      provided that they have high affinities for their target in vivo. An approach to
      improve a peptide ligand's affinity for its target is to make this interaction
      covalent and irreversible. For this purpose, we evaluated a (64)Cu-labeled
      affinity peptide tag, (64)Cu-L19K-(5-fluoro-2,4-dinitrobenzene) ((64)Cu-L19K
      FDNB), which binds covalently and irreversibly to vascular endothelial growth
      factor (VEGF) as a PET imaging agent. We compared the in vivo properties of
      (64)Cu-L19K-FDNB in VEGF-expressing tumor xenografts with its noncovalent binding
      analogs, (64)Cu-L19K-(2,4-dinitrophenyl) ((64)Cu-L19K-DNP) and (64)Cu-L19K.
      METHODS: The L19K peptide (GGNECDIARMWEWECFERK-CONH2) was constructed with 1,4,7
      triazacyclononane-1,4,7-triacetic acid at the N terminus for radiolabeling with
      (64)Cu with a polyethylene glycol spacer between peptide and chelate. 1,5
      difluoro-2,4-dinitrobenzene was conjugated at the C-terminal lysine for cross
      linking to VEGF, resulting in L19K-FDNB. (64)Cu-L19K-FDNB was assayed for
      covalent binding to VEGF in vitro. As a control, L19K was conjugated to 1-fluoro
      2,4-dinitrobenzene, resulting in L19K-DNP. PET imaging and biodistribution
      studies of (64)Cu-L19K-FDNB, (64)Cu-L19K-DNP, and the native (64)Cu-L19K were
      compared in HCT-116 xenografts. Blocking studies of (64)Cu-L19K-FDNB was
      performed with a coinjection of excess unlabeled L19K-FDNB. RESULTS: In vitro
      binding studies confirmed the covalent and irreversible binding of (64)Cu-L19K
      FDNB to VEGF, whereas (64)Cu-L19K-DNP and (64)Cu-L19K did not bind covalently.
      PET imaging showed higher tumor uptake with (64)Cu-L19K-FDNB than with (64)Cu
      L19K-DNP and (64)Cu-L19K, with mean standardized uptake values of 0.62 +/- 0.05,
      0.18 +/- 0.06, and 0.34 +/- 0.14, respectively, at 24 h after injection (P <
      0.05), and 0.53 +/- 0.05, 0.32 +/- 0.14, and 0.30 +/- 0.09, respectively, at 48 h
      after injection (P < 0.05). Blocking studies with (64)Cu-L19K-FDNB in the
      presence of excess unlabeled peptide showed a 53% reduction in tumor uptake at 48
      h after injection. CONCLUSION: In this proof-of-concept study, the use of a
      covalent binding peptide ligand against VEGF improves tracer accumulation at the
      tumor site in vivo, compared with its noncovalent binding peptide analogs. This
      technique is a promising tool to enhance the potency of peptide probes as imaging
      agents.

PMID- 24732154
TI  - Molecular imaging reveals trastuzumab-induced epidermal growth factor receptor
      downregulation in vivo.
AB  - Previous in vitro studies demonstrated that treating tumors expressing both
      epidermal growth factor receptor (EGFR) and human epidermal growth factor
      receptor 2 with trastuzumab resulted in increased EGFR homodimerization and
      subsequent rapid downregulation of EGFR. We investigated whether molecular
      imaging using near-infrared fluorescence (NIRF) imaging and PET probes could
      sensitively detect trastuzumab-induced EGFR downregulation in vivo. METHODS: The
      F(ab')2 antibody fragment PaniF(ab')2 was generated by digesting the anti-EGFR
      monoclonal antibody panitumumab. PaniF(ab')2 was labeled with either a NIRF dye
      or (68)Ga, and optical imaging and small-animal PET imaging of Dye-PaniF(ab')2
      and (68)Ga-PaniF(ab')2, respectively, were performed in HT-29 tumor-bearing nude
      mice treated with trastuzumab or untreated control. RESULTS: Longitudinal NIRF
      imaging studies revealed significantly reduced tumor uptake of Dye-PaniF(ab')2 on
      days 5 and 7 in trastuzumab-treated HT-29 tumors, compared with control. Western
      blotting confirmed the downregulation of EGFR after treatment with trastuzumab.
      Small-animal PET on day 5 after trastuzumab treatment also demonstrated decreased
      (68)Ga-PaniF(ab')2 uptake in trastuzumab-treated HT-29 tumors. The tumor uptake
      value of (68)Ga-PaniF(ab')2 obtained from PET imaging had an excellent linear
      correlation with the uptake value measured using biodistribution. CONCLUSION: The
      downregulation of EGFR induced by trastuzumab treatment could be detected
      noninvasively using optical and PET imaging. This molecular imaging strategy
      could provide a dynamic readout of changes in the tumor signaling and may
      facilitate the noninvasive monitoring of the early tumor response to drug
      treatment.

PMID- 24732155
TI  - Imaging the folate receptor on cancer cells with 99mTc-etarfolatide: properties,
      clinical use, and future potential of folate receptor imaging.
AB  - Folate receptor (FR) can be used as a therapeutic target because of its
      expression on different epithelial cancers, such as ovarian, non-small cell lung,
      endometrial, and breast cancer. Assessing FR expression in tumors may help to
      identify patients who can benefit from FR-targeted therapeutics, such as
      vintafolide and farletuzumab. Different methods exist to detect FR expression.
      Tissue sampling has limited clinical utility, mainly because it requires an
      invasive procedure. (99m)Tc-etarfolatide, a (99m)Tc-labeled folate conjugate, is
      in late-phase trials in Europe and the United States. It allows noninvasive,
      whole-body imaging of the FR. This review focuses on this FR-imaging agent and
      how it may be used to direct FR-targeted therapy. 

PMID- 24732156
TI  - Introduction to tobacco control supplement.
AB  - Electronic cigarettes (e-cigarettes) have recently gained significant attention
      in the marketplace and in the media. However, limited information is available
      about the worldwide impact of e-cigarettes; most public health officials are
      calling for more data so they can more fully understand the potential risks and
      benefits of e-cigarettes in order to inform regulatory action. In the USA, e
      cigarettes that are marketed as tobacco products are not currently regulated by
      the Food and Drug Administration (FDA). However, having a continuum of nicotine
      containing products that cross jurisdictional lines within the FDA in the future
      would create the potential (and the need) for a comprehensive nicotine strategy
      at the FDA. As part of developing the most appropriate approach to e-cigarette
      regulation, FDA Center for Tobacco Products scientists have been reviewing the
      available literature to determine the state of e-cigarette knowledge and have
      identified research areas that could be addressed. This supplement provides a
      summary of the current knowledge and research gaps pertaining to e-cigarettes
      with regards to product design, chemistry and toxicology of e-liquid and aerosol
      constituents, human factor-based risk factors, abuse liability, clinical
      pharmacology and human health effects, paediatric issues, and environmental
      issues. 

PMID- 24732157
TI  - Chemical evaluation of electronic cigarettes.
AB  - OBJECTIVE: To review the available evidence evaluating the chemicals in refill
      solutions, cartridges, aerosols and environmental emissions of electronic
      cigarettes (e-cigarettes). METHODS: Systematic literature searches were conducted
      to identify research related to e-cigarettes and chemistry using 5 reference
      databases and 11 search terms. The search date range was January 2007 to
      September 2013. The search yielded 36 articles, of which 29 were deemed relevant
      for analysis. RESULTS: The levels of nicotine, tobacco-specific nitrosamines
      (TSNAs), aldehydes, metals, volatile organic compounds (VOCs), flavours, solvent
      carriers and tobacco alkaloids in e-cigarette refill solutions, cartridges,
      aerosols and environmental emissions vary considerably. The delivery of nicotine
      and the release of TSNAs, aldehydes and metals are not consistent across
      products. Furthermore, the nicotine level listed on the labels of e-cigarette
      cartridges and refill solutions is often significantly different from measured
      values. Phenolic compounds, polycyclic aromatic hydrocarbons and drugs have also
      been reported in e-cigarette refill solutions, cartridges and aerosols. Varying
      results in particle size distributions of particular matter emissions from e
      cigarettes across studies have been observed. Methods applied for the generation
      and chemical analyses of aerosols differ across studies. Performance
      characteristics of e-cigarette devices also vary across and within brands.
      CONCLUSIONS: Additional studies based on knowledge of e-cigarette user behaviours
      and scientifically validated aerosol generation and chemical analysis methods
      would be helpful in generating reliable measures of chemical quantities. This
      would allow comparisons of e-cigarette aerosol and traditional smoke constituent
      levels and would inform an evaluation of the toxicity potential of e-cigarettes.

PMID- 24732158
TI  - Electronic cigarettes in the USA: a summary of available toxicology data and
      suggestions for the future.
AB  - OBJECTIVE: To review the available evidence evaluating the toxicological profiles
      of electronic cigarettes (e-cigarettes) in order to understand the potential
      impact of e-cigarettes on individual users and the public health. METHODS:
      Systematic literature searches were conducted between October 2012 and October
      2013 using five electronic databases. Search terms such as 'e-cigarettes' and
      'electronic delivery devices' were used to identify the toxicology information
      for e-cigarettes. RESULTS: As of October 2013, the scientific literature contains
      very limited information regarding the toxicity of e-cigarettes commercially
      available in the USA. While some preliminary toxicology data suggests that e
      cigarette users are exposed to lower levels of toxicants relative to cigarette
      smokers, the data available is extremely limited at this time. At present, there
      is insufficient toxicological data available to perform thorough risk assessment
      analyses for e-cigarettes; few toxicology studies evaluating e-cigarettes have
      been conducted to date, and standard toxicological testing paradigms have not
      been developed for comparing disparate types of tobacco products such as e
      cigarettes and traditional cigarettes. CONCLUSIONS: Overall, the limited
      toxicology data on e-cigarettes in the public domain is insufficient to allow a
      thorough toxicological evaluation of this new type of tobacco product. In the
      future, the acquisition of scientific datasets that are derived from
      scientifically robust standard testing paradigms, include comprehensive chemical
      characterisation of the aerosol, provide information on users' toxicant exposure
      levels, and from studies replicated by independent researchers will improve the
      scientific community's ability to perform robust toxicological evaluations of e
      cigarettes.

PMID- 24732159
TI  - Electronic cigarettes: abuse liability, topography and subjective effects.
AB  - OBJECTIVE: To review the available evidence evaluating the abuse liability,
      topography, subjective effects, craving and withdrawal suppression associated
      with e-cigarette use in order to identify information gaps and provide
      recommendations for future research. METHODS: Literature searches were conducted
      between October 2012 and January 2014 using five electronic databases. Studies
      were included in this review if they were peer-reviewed scientific journal
      articles evaluating clinical laboratory studies, national surveys or content
      analyses. RESULTS: A total of 15 peer-reviewed articles regarding behavioural use
      and effects of e-cigarettes published between 2010 and 2014 were included in this
      review. Abuse liability studies are limited in their generalisability. Topography
      (consumption behaviour) studies found that, compared with traditional cigarettes,
      e-cigarette average puff duration was significantly longer, and e-cigarette use
      required stronger suction. Data on e-cigarette subjective effects (such as
      anxiety, restlessness, concentration, alertness and satisfaction) and withdrawal
      suppression are limited and inconsistent. In general, study data should be
      interpreted with caution, given limitations associated with comparisons of novel
      and usual products, as well as the possible effects associated with subjects'
      previous experience/inexperience with e-cigarettes. CONCLUSIONS: Currently, very
      limited information is available on abuse liability, topography and subjective
      effects of e-cigarettes. Opportunities to examine extended e-cigarette use in a
      variety of settings with experienced e-cigarette users would help to more fully
      assess topography as well as behavioural and subjective outcomes. In addition,
      assessment of 'real-world' use, including amount and timing of use and responses
      to use, would clarify behavioural profiles and potential adverse health effects.

PMID- 24732160
TI  - Electronic cigarettes and nicotine clinical pharmacology.
AB  - OBJECTIVE: To review the available literature evaluating electronic cigarette (e
      cigarette) nicotine clinical pharmacology in order to understand the potential
      impact of e-cigarettes on individual users, nicotine dependence and public
      health. METHODS: Literature searches were conducted between 1 October 2012 and 30
      September 2013 using key terms in five electronic databases. Studies were
      included in the review if they were in English and publicly available; non
      clinical studies, conference abstracts and studies exclusively measuring nicotine
      content in e-cigarette cartridges were excluded from the review. RESULTS:
      Nicotine yields from automated smoking machines suggest that e-cigarettes deliver
      less nicotine per puff than traditional cigarettes, and clinical studies indicate
      that e-cigarettes deliver only modest nicotine concentrations to the
      inexperienced e-cigarette user. However, current e-cigarette smokers are able to
      achieve systemic nicotine and/or cotinine concentrations similar to those
      produced from traditional cigarettes. Therefore, user experience is critically
      important for nicotine exposure, and may contribute to the products' ability to
      support and maintain nicotine dependence. CONCLUSIONS: Knowledge about e
      cigarette nicotine pharmacology remains limited. Because a user's e-cigarette
      experience may significantly impact nicotine delivery, future nicotine
      pharmacokinetic and pharmacodynamic studies should be conducted in experienced
      users to accurately assess the products' impact on public health.

PMID- 24732161
TI  - Electronic cigarettes: human health effects.
AB  - OBJECTIVE: With the rapid increase in use of electronic nicotine delivery systems
      (ENDS), such as electronic cigarettes (e-cigarettes), users and non-users are
      exposed to the aerosol and product constituents. This is a review of published
      data on the human health effects of exposure to e-cigarettes and their
      components. METHODS: Literature searches were conducted through September 2013
      using multiple electronic databases. RESULTS: Forty-four articles are included in
      this analysis. E-cigarette aerosols may contain propylene glycol, glycerol,
      flavourings, other chemicals and, usually, nicotine. Aerosolised propylene glycol
      and glycerol produce mouth and throat irritation and dry cough. No data on the
      effects of flavouring inhalation were identified. Data on short-term health
      effects are limited and there are no adequate data on long-term effects. Aerosol
      exposure may be associated with respiratory function impairment, and serum
      cotinine levels are similar to those in traditional cigarette smokers. The high
      nicotine concentrations of some products increase exposure risks for non-users,
      particularly children. The dangers of secondhand and thirdhand aerosol exposure
      have not been thoroughly evaluated. CONCLUSIONS: Scientific evidence regarding
      the human health effects of e-cigarettes is limited. While e-cigarette aerosol
      may contain fewer toxicants than cigarette smoke, studies evaluating whether e
      cigarettes are less harmful than cigarettes are inconclusive. Some evidence
      suggests that e-cigarette use may facilitate smoking cessation, but definitive
      data are lacking. No e-cigarette has been approved by FDA as a cessation aid.
      Environmental concerns and issues regarding non-user exposure exist. The health
      impact of e-cigarettes, for users and the public, cannot be determined with
      currently available data.

PMID- 24732162
TI  - Electronic cigarettes: product characterisation and design considerations.
AB  - OBJECTIVE: To review the available evidence regarding electronic cigarette (e
      cigarette) product characterisation and design features in order to understand
      their potential impact on individual users and on public health. METHODS:
      Systematic literature searches in 10 reference databases were conducted through
      October 2013. A total of 14 articles and documents and 16 patents were included
      in this analysis. RESULTS: Numerous disposable and reusable e-cigarette product
      options exist, representing wide variation in product configuration and component
      functionality. Common e-cigarette components include an aerosol generator, a flow
      sensor, a battery and a nicotine-containing solution storage area. e-cigarettes
      currently include many interchangeable parts, enabling users to modify the
      character of the delivered aerosol and, therefore, the product's 'effectiveness'
      as a nicotine delivery product. Materials in e-cigarettes may include metals,
      rubber and ceramics. Some materials may be aerosolised and have adverse health
      effects. Several studies have described significant performance variability
      across and within e-cigarette brands. Patent applications include novel product
      features designed to influence aerosol properties and e-cigarette efficiency at
      delivering nicotine. CONCLUSIONS: Although e-cigarettes share a basic design,
      engineering variations and user modifications result in differences in nicotine
      delivery and potential product risks. e-cigarette aerosols may include harmful
      and potentially harmful constituents. Battery explosions and the risks of
      exposure to the e-liquid (especially for children) are also concerns. Additional
      research will enhance the current understanding of basic e-cigarette design and
      operation, aerosol production and processing, and functionality. A standardised e
      cigarette testing regime should be developed to allow product comparisons.

PMID- 24732163
TI  - The impact of electronic cigarettes on the paediatric population.
AB  - OBJECTIVE: To review the impact of electronic cigarettes (e-cigarettes) on
      children. METHODS: Five electronic databases were searched through 31 December
      2013. Studies in English that included data for children younger than 18 years of
      age were included. In addition, relevant data from articles identified during
      searches of the e-cigarette literature, relevant state survey data and paediatric
      voluntary adverse event reports submitted to the US Food and Drug Administration
      (FDA) were reviewed and included. RESULTS: Use of e-cigarettes by youth is
      increasing and is not limited to traditional cigarette smokers. Data regarding
      the reasons for youth e-cigarette initiation and ongoing use are limited. The
      effects of e-cigarette marketing and the availability of flavoured e-liquids on
      youth use are unknown. The abuse liability of e-cigarettes in youth is also not
      known. Unintentional exposures to e-cigarettes and e-liquids have been reported
      in children. The number of e-cigarette-related reports received by poison centres
      is increasing. No data are available on secondhand and thirdhand e-cigarette
      aerosol exposures in children. CONCLUSIONS: Data on the impact of e-cigarettes on
      children are extremely limited. The available data indicate that youth awareness
      is high and use is increasing rapidly. The extent to which e-cigarette use in
      youth will result in nicotine dependence and subsequent use of other tobacco
      products is unknown. e-cigarettes present risks of unintentional nicotine
      exposure and are potential choking hazards. A greater understanding of the impact
      of e-cigarettes on children is needed and will be important in the evaluation of
      the effects of these products on the public health.

PMID- 24732164
TI  - Electronic cigarettes: incorporating human factors engineering into risk
      assessments.
AB  - OBJECTIVE: A systematic review was conducted to evaluate the impact of human
      factors (HF) on the risks associated with electronic cigarettes (e-cigarettes)
      and to identify research gaps. HF is the evaluation of human interactions with
      products and includes the analysis of user, environment and product complexity.
      Consideration of HF may mitigate known and potential hazards from the use and
      misuse of a consumer product, including e-cigarettes. METHODS: Five databases
      were searched through January 2014 and publications relevant to HF were
      incorporated. Voluntary adverse event (AE) reports submitted to the US Food and
      Drug Administration (FDA) and the package labelling of 12 e-cigarette products
      were analysed. RESULTS: No studies specifically addressing the impact of HF on e
      cigarette use risks were identified. Most e-cigarette users are smokers, but data
      on the user population are inconsistent. No articles focused specifically on e
      cigarette use environments, storage conditions, product operational requirements,
      product complexities, user errors or misuse. Twelve published studies analysed e
      cigarette labelling and concluded that labelling was inadequate or misleading.
      FDA labelling analysis revealed similar concerns described in the literature. AE
      reports related to design concerns are increasing and fatalities related to
      accidental exposure and misuse have occurred; however, no publications evaluating
      the relationship between AEs and HF were identified. CONCLUSIONS: The HF
      impacting e-cigarette use and related hazards are inadequately characterised.
      Thorough analyses of user-product-environment interfaces, product complexities
      and AEs associated with typical and atypical use are needed to better incorporate
      HF engineering principles to inform and potentially reduce or mitigate the
      emerging hazards associated with e-cigarette products.

PMID- 24732165
TI  - Research gaps related to the environmental impacts of electronic cigarettes.
AB  - OBJECTIVE: To consider the research gaps related to the environmental impacts of
      electronic cigarettes due to their manufacture, use and disposal. METHODS:
      Literature searches were conducted through December 2013. Studies were included
      in this review if they related to the environmental impacts of e-cigarettes.
      RESULTS: Scientific information on the environmental impacts of e-cigarette
      manufacturing, use and disposal is very limited. No studies formally evaluated
      the environmental impacts of the manufacturing process or disposal of components,
      including batteries. Four studies evaluated potential exposure to secondhand e
      cigarette aerosol, an indication of impacts on indoor air quality. A 2010 survey
      of six e-cigarette models found that none of the products provided disposal
      instructions for spent cartridges containing nicotine. Notably, some e-cigarette
      manufacturers claim their e-cigarettes are 'eco-friendly' or 'green', despite the
      lack of any supporting data or environmental impact studies. Some authors argue
      that such advertising may boost sales and increase e-cigarette appeal, especially
      among adolescents. CONCLUSIONS: Little is known about the environmental impacts
      of e-cigarettes, and a number of topics could be further elucidated by additional
      investigation. These topics include potential environmental impacts related to
      manufacturing, use and disposal. The environmental impacts of e-cigarette
      manufacturing will depend upon factory size and the nicotine extracting method
      used. The environmental impacts of e-cigarette use will include chemical and
      aerosol exposure in the indoor environment. The environmental impacts of disposal
      of e-cigarette cartridges (which contain residual nicotine) and disposal of e
      cigarettes (which contain batteries) represent yet another environmental concern.

PMID- 24732166
TI  - Estimating TSCI incidence worldwide: a long road to drive.

PMID- 24732167
TI  - Neurogenic bladder in patients with traumatic spinal cord injury: treatment and
      follow-up.
AB  - STUDY DESIGN: Multi-center, cross-sectional study. OBJECTIVES: Our aim was to
      evaluate the treatment methods and follow-up of neurogenic bladder in patients
      with traumatic spinal cord injury retrospectively using a questionnaire. SETTING:
      Turkey. METHODS: Three hundred and thirty-seven patients who had spinal cord
      injury for at least 2 years were enrolled from six centers in the neurogenic
      bladder study group. They were asked to fill-out a questionnaire about treatments
      they received and techniques they used for bladder management. RESULTS: The study
      included 246 male and 91 female patients with a mean age of 42+/-14 years.
      Intermittent catheterization (IC) was performed in 77.9% of the patients, 3.8%
      had indwelling catheters, 13.8% had normal spontaneous micturition, 2.6%
      performed voiding maneuvers, 1.3% used diapers and 0.6% used condom catheters. No
      gender difference was found regarding the techniques used in bladder
      rehabilitation (P>0.05). Overall, 63.2% of patients used anticholinergic drugs;
      anticholinergic drug use was similar between genders (P>0.05). The most common
      anticholinergic drug used was oxybutynin (40.3%), followed by trospium (32.6%),
      tolterodine (19.3%) darifenacin (3.3%), propiverine (3.3%) and solifenacin
      (1.1%). The specialties of the physicians who first prescribed the
      anticholinergic drug were physiatrists (76.2%), urologists (22.1%) and
      neurologists (1.7%). Only four patients had previously received injections of
      botulinum-toxin-A into the detrusor muscle and three of them stated that their
      symptoms showed improvement. Most of the patients (77%) had regular follow-up
      examinations, including urine cultures, urinary system ultrasound and urodynamic
      tests, when necessary; the reasons for not having regular control visits were
      living distant from hospital (15.3%) and monetary problems (7.7%). Of the
      patients, 42.7% did not experience urinary tract infections (UTI), 36.4% had
      bacteriuria but no UTI episodes with fever, 15.9% had 1-2 clinical UTI episodes
      per year and 5% had ?3 clinical UTIs. The clinical characteristics of patients
      with and without UTI (at least one symptomatic UTI during 1 year) were similar
      (P>0.05). The frequency of symptomatic UTI was similar in patients using
      different bladder management techniques (P>0.05). CONCLUSION: The most frequently
      used technique for bladder rehabilitation in patients with SCI was IC (77.9%). In
      all, 63.2% of patients used anticholinergic drugs, oxybutynin being the most
      commonly used drug. Also, 77% of patients had regular control visits for
      neurogenic bladder; 42.7% did not experience any UTIs.

PMID- 24732168
TI  - Outcomes of whole-body computed tomography in spinal cord-injured patients with
      sepsis.
AB  - STUDY DESIGN: Retrospective case series. OBJECTIVES: To evaluate the efficacy of
      body computed tomography (CT) in spinal cord injury (SCI) patients with sepsis.
      SETTING: Specialist acute care and rehabilitation SCI centre in United Kingdom.
      METHODS: Patients with SCI and suspected or known sepsis, who had CT of the
      chest, abdomen and pelvis, over a 4-year period, were identified. Only patients
      who fulfilled the definition of sepsis or severe sepsis were included. Their
      medical notes and CT scans were reviewed and clinical outcomes and radiological
      findings recorded. RESULTS: Twenty-two patients with sepsis were identified
      including seven categorised as having severe sepsis. A specific radiological
      diagnosis was found in three patients (14%) and non-specific findings were found
      in 15 patients (68%). CONCLUSION: Although in the majority of cases, the findings
      were non-specific, a small number of patients had significant pathology
      identified by CT, which influenced their management significantly.

PMID- 24732169
TI  - Effect of a mixed kinesio taping-compression technique on quality of life and
      clinical and gait parameters in postmenopausal women with chronic venous
      insufficiency: double-blinded, randomized controlled trial.
AB  - OBJECTIVE: To investigate the short-term effect of a mixed Kinesio taping (KT)
      model on range of ankle motion (ROAM), gait, pain, perimeter of lower limbs, and
      quality of life in postmenopausal women with chronic venous insufficiency (CVI).
      DESIGN: Double-blinded, randomized controlled trial. SETTING: Clinical setting.
      PARTICIPANTS: Consecutive postmenopausal women (N=130; mean age +/- SD, 65.44+/
      14.7y) with mild CVI. No participant withdrew because of adverse effects.
      INTERVENTION: Participants were randomly assigned to either (1) an experimental
      group to receive a mixed KT-compression treatment following KT recommendations
      for gastrocnemius muscle enhancement and functional correction of the ankle, and
      adding 2 tapes to simulate traditional compression bandages (no KT guidelines);
      or (2) a placebo control group for sham KT. Both interventions were performed 3
      times a week during a 4-week period. MAIN OUTCOME MEASURES: ROAM, gait, pain,
      perimeter of right and left lower limb, and quality of life were assessed at
      baseline and 48 hours posttreatment. RESULTS: Quality of life was better in the
      intervention group by a mean of 8.76 points (95% confidence interval [CI], 4.96
      12.55). The experimental group also showed significant pre-/posttreatment
      improvements in both lower limbs in gait dorsiflexion ROAM (95% CI, 1.02-2.49),
      cadence (95% CI, 3.45-1.47), stride length (95% CI, 21.48-10.83), step length
      (95% CI, 1.68-6.61), stance phase (95% CI, 61-107), and foot (95% CI, .56-.92)
      and malleolus (95% CI, 1.15-1.63) circumference. None of these variables were
      significantly modified in the placebo group. Both groups reported a significant
      reduction in pain. CONCLUSIONS: Ankle dorsiflexion during gait, walking
      parameters, peripheral edema, venous pain, and quality of life remain improved in
      patients with CVI at 1 month after mixed KT-compression therapy. KT may have a
      placebo effect on pain perception.

PMID- 24732170
TI  - Why disability and rehabilitation specialists should lead the way in patient
      reported outcomes.

PMID- 24732171
TI  - Towards a better measure of brain injury outcome: new measures or a new metric?

PMID- 24732173
TI  - Coagulation competence and fluid recruitment after moderate blood loss in young
      men.
AB  - The coagulation system is activated by a reduction of the central blood volume
      during orthostatic stress and lower body negative pressure suggesting that also a
      blood loss enhances coagulation. During bleeding, however, the central blood
      volume is supported by fluid recruitment to the circulation and redistribution of
      the blood volume. In eight supine male volunteers (24 +/- 3 years, blood volume
      of 6.9 +/- 0.7 l; mean +/- SD), 2 * 450 ml blood was withdrawn over ~ 30 min
      while cardiovascular variables were monitored. Coagulation was evaluated by
      thrombelastography, and fluid recruitment was estimated by red blood cell count.
      Withdrawing 900 ml blood increased heart rate (62 +/- 7 to 69 +/- 13 bpm, P <
      0.05; mean +/- SD) and reduced stroke volume (113 +/- 12 to 96 +/- 14 ml, P <
      0.05) leaving cardiac output, mean arterial pressure, and total peripheral
      resistance unchanged and, furthermore, reduced red blood cell count (4.80 +/-
      0.33 to 4.64 +/- 0.37 * 10(12) cells l(-1), P < 0.05) indicating that 218 +/- 173
      ml fluid was recruited to the circulation. Withdrawing 450 ml blood reduced the
      time until initial fibrin formation (R: 6.5 +/- 0.9 to 5.1 +/- 1.0 min, P <
      0.01), whereas the rate of clot formation increased after withdrawal of 900 ml
      blood (alpha-Angle: 66 +/- 4 to 70 +/- 3 deg, P < 0.01). Clot strength (maximal
      amplitude: 57 +/- 4 mm), clot lysis 30 min after maximal amplitude (LY30: 0.8% [0
      3.5%] (median [range])), and platelet count (218 +/- 25 * 10(9) l(-1)) were
      unaffected. For supine males, ~ 25% of a moderate blood loss is compensated by
      fluid recruitment to the circulation, which may explain the minor cardiovascular
      response. Yet, a blood loss of 450 ml accelerates coagulation, and this is
      further accentuated when blood loss is 900 ml.

PMID- 24732174
TI  - Laboratory-monitored fondaparinux and coagulation activity in association with
      total hip replacement.
AB  - Fondaparinux, indirect factor Xa (FXa) inhibitor, is recommended for
      thromboprophylaxis for high-risk patients undergoing major orthopedic surgery. We
      evaluated the prothrombotic state and anticoagulant intensity of fondaparinux
      (2.5 mg daily) after total hip replacement (THR). Twenty patients underwent THR -
      seven bilateral and 13 unilateral. Blood samples were collected preoperatively
      and at 6 h, 8 h (2 h after fondaparinux), 1 day (12-14 h after fondaparinux), and
      4 weeks (12-14 h after fondaparinux) postoperatively. Antithrombin (AT),
      fibrinogen, factor VIII activity, coagulation times, thrombin-AT (TAT) complex, D
      dimer, C-reactive protein, prothrombinase-induced clotting time (PiCT) and anti
      Xa activity were measured. The latter two were also tested after plasma spiking
      with fondaparinux 0-1.25 MUg/ml. In spiked prophylactic fondaparinux samples (0
      0.25 MUg/ml), PiCT and anti-Xa activity correlated (r = 0.84) better than in the
      patient samples (r = 0.35). On the first day, anti-Xa activity and PiCT
      dissociated, and PiCT lost sensitivity for fondaparinux. AT decreased but stayed
      within the normal range, whereas TAT complex and D-dimer peaked at 6 h as signs
      of thrombin generation. On the first postoperative day, TAT and D-dimer halved.
      Bilateral THR associated with higher TAT and D-dimer levels up to 4 weeks.
      Perioperative FVIII levels were not affected, but were elevated in both groups
      (range 191-211%) after 4 weeks. Anti-Xa activity detected prophylactic
      fondaparinux with higher sensitivity than PiCT in vitro, but even more so in
      vivo. Thus, PiCT is not the method of choice to assess fondaparinux at least in
      association with THR. THR, bilateral more than unilateral, increased thrombin
      generation and D-dimer 7-11-fold early after surgery. Factor VIII activity and D
      dimer remained elevated even after 4 weeks despite the compliant
      thromboprophylaxis with fondaparinux.

PMID- 24732172
TI  - PDGFRalpha up-regulation mediated by sonic hedgehog pathway activation leads to
      BRAF inhibitor resistance in melanoma cells with BRAF mutation.
AB  - Control of BRAF(V600E) metastatic melanoma by BRAF inhibitor (BRAF-I) is limited
      by intrinsic and acquired resistance. Growth factor receptor up-regulation is
      among the mechanisms underlying BRAF-I resistance of melanoma cells. Here we
      demonstrate for the first time that PDGFRalpha up-regulation causes BRAF-I
      resistance. PDGFRalpha inhibition by PDGFRalpha-specific short hairpin (sh)RNA
      and by PDGFRalpha inhibitors restores and increases melanoma cells' sensitivity
      to BRAF-I in vitro and in vivo. This effect reflects the inhibition of ERK and
      AKT activation which is associated with BRAF-I resistance of melanoma cells.
      PDGFRalpha up-regulation is mediated by Sonic Hedgehog Homolog (Shh) pathway
      activation which is induced by BRAF-I treatment. Similarly to PDGFRalpha
      inhibition, Shh inhibition by LDE225 restores and increases melanoma cells'
      sensitivity to BRAF-I. These effects are mediated by PDGFRalpha down-regulation
      and by ERK and AKT inhibition. The clinical relevance of these data is indicated
      by the association of PDGFRalpha up-regulation in melanoma matched biopsies of
      BRAF-I +/- MEK inhibitor treated patients with shorter time to disease
      progression and less tumor regression. These findings suggest that monitoring
      patients for early PDGFRalpha up-regulation will facilitate the identification of
      those who may benefit from the treatment with BRAF-I in combination with
      clinically approved PDGFRalpha or Shh inhibitors. 

PMID- 24732175
TI  - Testosterone, thrombophilia, thrombosis.
AB  - We assessed previously undiagnosed thrombophilia-hypofibrinolysis in 11
      testosterone (T)-taking men, five of whom developed deep venous thrombosis (DVT),
      four pulmonary embolism, one spinal cord infarction, and one osteonecrosis 3.5
      months (median) after starting T gel (50-160 mg/day) or T intramuscular (50-250
      mg/week). In the order of referral because of thrombosis after starting T,
      thrombophilia-hypofibrinolysis was studied in 11 men, and, separately, in two
      control groups without thrombosis - 44 healthy normal male controls and 39
      healthy men taking T. Nine men had DVT or DVT-pulmonary embolism after 3.5 months
      (median) on T, one spinal cord infarction after 5 days on T, and one had
      osteonecrosis (knee and then hip osteonecrosis after 6 and 18 months on T). Four
      of the 11 men (36%) had high factor VIII (>=150%) vs. one of 42 (2%) controls (P
      = 0.005), and vs. one of 25 (4%) T-controls, (P = 0.023). Of the 11 men, two
      (18%) had factor V Leiden heterozygosity vs. none of 44 controls, (P = 0.04) and
      vs. none of 39 T-controls(P = 0.045). Of the 11 men, three had 4G4G plasminogen
      activator inhibitor-1 homozygosity, one prothrombin G20210A heterozygosity, one
      low protein S, and one high factor XI. When T was continued, second DVT-pulmonary
      embolism recurred in three of 11 men despite adequate anticoagulation. T
      interacts with thrombophilia-hypofibrinolysis leading to thrombosis. Men
      sustaining DVT-pulmonary embolism-osteonecrosis on T should be studied for
      thrombophilia. Continuation of T in thrombophilic men appears to be
      contraindicated because of recurrent thrombosis despite adequate anticoagulation.
      Before starting T, to prevent T-associated thrombosis, we recommend measures of
      factor V Leiden, factor VIII, and the prothrombin gene. 

PMID- 24732176
TI  - Iron and carbon monoxide enhance coagulation and attenuate fibrinolysis by
      different mechanisms.
AB  - Two parallel lines of investigation elucidating novel mechanisms by which iron
      (scanning electron microscopy-based) and carbon monoxide (viscoelastic-based)
      enhance coagulation and diminish fibrinolysis have emerged over the past few
      years. However, a multimodal approach to ascertain the effects of iron and carbon
      monoxide remained to be performed. Such investigation could be important, as iron
      and carbon monoxide are two of the products of heme catabolism via heme oxygenase
      1, an enzyme upregulated in a variety of disease states associated with
      thrombophilia. Human plasma was exposed to ferric chloride, carbon monoxide
      derived from carbon monoxide-releasing molecule-2, or their combination.
      Viscoelastic studies demonstrated ferric chloride and carbon monoxide mediated
      enhancement of velocity of growth, and final clot strength, with the combination
      of the two molecules noted to have all the prothrombotic kinetic effects of
      either separately. Parallel ultrastructural studies demonstrated separate types
      of fibrin polymer cross-linking and matting in plasma exposed to ferric chloride
      and carbon monoxide, with the combination sharing features of each molecule. In
      conclusion, we present the first evidence that iron and carbon monoxide interact
      with key coagulation and fibrinolytic processes, resulting in thrombi that begin
      to form more quickly, grow faster, become stronger, and are more resistant to
      lysis. 

PMID- 24732178
TI  - Pharmacogenetics of pemetrexed combination therapy in lung cancer: pathway
      analysis reveals novel toxicity associations.
AB  - Identification of polymorphisms that influence pemetrexed tolerability could lead
      to individualised treatment regimens and improve quality of life. Twenty-eight
      polymorphisms within eleven candidate genes were genotyped using the Illumina
      Human Exome v1.1 BeadChip and tested for their association with the clinical
      outcomes of non-small cell lung cancer and mesothelioma patients receiving
      pemetrexed/platinum doublet chemotherapy (n=136). GGH rs11545078 was associated
      with a reduced incidence of grade ?3 toxicity within the first four cycles of
      therapy (odds ratio (OR) 0.25, P=0.018), as well as reduced grade ?3
      haematological toxicity (OR 0.13, P=0.048). DHFR rs1650697 conferred an increased
      risk of grade ?3 toxicity (OR 2.14, P=0.034). Furthermore, FOLR3 rs61734430 was
      associated with an increased likelihood of disease progression at mid-treatment
      radiological evaluation (OR 4.05, P=0.023). Polymorphisms within SLC19A1
      (rs3788189, rs1051298 and rs914232) were associated with overall survival. This
      study confirms previous pharmacogenetic associations and identifies novel markers
      of pemetrexed toxicity. 

PMID- 24732177
TI  - The A2 gene of alcelaphine herpesvirus-1 is a transcriptional regulator affecting
      cytotoxicity in virus-infected T cells but is not required for malignant
      catarrhal fever induction in rabbits.
AB  - Alcelaphine herpesvirus-1 (AlHV-1) causes malignant catarrhal fever (MCF). The A2
      gene of AlHV-1 is a member of the bZIP transcription factor family. We wished to
      determine whether A2 is a virulence gene or not and whether it is involved in
      pathogenesis by interference with host transcription pathways. An A2 gene
      knockout (A2DeltaAlHV-1) virus, revertant (A2revAlHV-1) virus, and wild-type
      virus (wtAlHV-1) were used to infect three groups of rabbits. A2DeltaAlHV-1
      infected rabbits succumbed to MCF, albeit with a delayed onset compared to the
      control groups, so A2 is not a critical virulence factor. Differential gene
      transcription analysis by RNAseq and qRT-PCR validation of a selection of these
      was performed in infected large granular lymphocyte (LGL) T cells obtained in
      culture from the MCF-affected animals. A2 was involved in the transcriptional
      regulation of immunological, cell cycle and apoptosis pathways. In particular,
      there was a bias towards gammadelta T cell receptor (TCR) expression and
      downregulation of alphabeta TCR. TCR signalling, apoptosis, cell cycle, IFN-gamma
      and NFAT pathways were affected. Of particular interest was partial inhibition of
      the cytotoxicity-associated pathways involving perforin and the granzymes A and B
      in the A2DeltaAlHV-1-infected LGLs compared to controls. In functional assays,
      A2DeltaAlHV-1-infected LGLs were significantly less cytotoxic than wtAlHV-1- and
      A2revAlHV-1-infected LGLs using rabbit corneal epithelial cells (SIRC) as
      targets. This implies that A2 is involved in a pathway enhancing the expression
      of LGL cytotoxicity. This is important as virus-infected T cell cytotoxicity in
      vivo has been suggested as a potential mechanism of disease induction in MCF.

PMID- 24732180
TI  - Healthy Stomach Initiative: the stomach in health and disease. Preface.

PMID- 24732179
TI  - Propofol protects human umbilical vein endothelial cells from cisplatin-induced
      injury.
AB  - The anticancer drug cisplatin can up-regulate endothelial adhesion molecule
      expression, and trigger vascular endothelial injury. Propofol, an intravenous
      anesthetic, can inhibit endothelial adhesion molecule expression in some
      situations. Here, we explored whether and how propofol improved cisplatin-induced
      up-regulation of endothelial adhesion molecules in human umbilical vein
      endothelial cells. Compared with control group, cisplatin reduced endothelial
      nitric oxide synthase dimer/monomer ratio, activated protein kinase C and
      enhanced endothelial nitric oxide synthase-Thr495 phosphorylation, decreased
      nitric oxide production, augmented intercellular adhesion molecule 1 expression
      and monocyte-endothelial adhesion. These cisplatin-mediated effects were
      attenuated by propofol treatment. Nomega-Nitro-L-arginine methyl ester
      hydrochloride, a nitric oxide synthase inhibitor, inhibited the effect of
      propofol on cisplatin-induced intercellular adhesion molecule 1 expression.
      Propofol improved cisplatin-mediated tetrahydrobiopterin reduction and
      nitrotyrosine overexpression. Compared with control group, cisplatin and PMA, a
      protein kinase C activator, both increased endothelial nitric oxide synthase
      Thr495 phosphorylation, while propofol and GFX, a protein kinase C inhibitor,
      both decreased cisplatin-induced endothelial nitric oxide synthase-Thr495
      phosphorylation. Our data indicated that propofol, via reducing cisplatin-induced
      endothelial nitric oxide synthase uncoupling and endothelial nitric oxide
      synthase-Thr495 phosphorylation, restored nitric oxide production, intercellular
      adhesion molecule 1 expression and monocyte-endothelial interaction.

PMID- 24732181
TI  - Digestive function of the stomach.
AB  - The core function of the human stomach is as an aid to digestion. The four key
      components of gastric digestive function are its function as a reservoir, acid
      secretion, enzyme secretion and its role in gastrointestinal motility. The
      reservoir capacity of the stomach allows it to increase its volume significantly
      while internal pressure increases only slightly. Acid secretion is a very
      important non-immunological defence against invading pathogens as well as being
      an important mechanism for vertebrates to have more complex diets. Stimulation of
      acid secretion involves the translocation of H+/K+-ATPases to the apical membrane
      of the parietal cell. The stomach is also an important endocrine organ producing
      an array of peptide hormones important for both enteric and non-enteric
      physiology including ghrelin and leptin. In addition to the reservoir function,
      the stomach also plays an important motility role as a pump, which anatomically
      is provided by the distal two thirds of the corpus, the antrum and the pylorus.
      This article examines those four functions and the role that they play in normal
      physiologic function and examines how they may play a role in pathologic states.

PMID- 24732182
TI  - Stomach--key player in the regulation of metabolism.
AB  - Although the stomach is often perceived as a crude, food-grinding, muscular bag,
      scientific breakthroughs have shown us that in the case of the stomach there is
      more than meets the eye. The endocrine function of the stomach is mainly exerted
      through the actions of ghrelin, an acylated peptide hormone that is the first
      known and so far most extensively studied endogenous orexigenic substance. The
      satiety-hunger balance is kept in check by many anorexigenic gut hormones among
      which is the deacylated form of ghrelin--desacyl ghrelin. The interplay of gut
      hormones affects the brain directly, as most gut hormones cross the blood-brain
      barrier and bind to their respective receptors in the central nervous system.
      Other hormones like obestatin and nesfatin are secreted from the stomach along
      with ghrelin, yet their physiological function is to be elucidated. The
      importance of the satiety-hunger balance can be seen in its most typical
      derangement--obesity. Some studies imply that ghrelin, along with other gut
      hormones, plays an important part in the pathophysiology of obesity. More
      importantly, it seems that the mechanisms by which bariatric surgery procedures
      induce weight loss are primarily based on changing the gut hormone levels,
      including ghrelin. If proven, ghrelin antagonists could be the renaissance of
      pharmacological obesity treatment.

PMID- 24732183
TI  - Lifestyle and gastric function.
AB  - The stomach has a range of functions, including chemical digestion and mechanical
      breakdown of food, temporary storage of bulk intake, and regulation of the
      passage of nutrients into the duodenum. Further gastric functions are the
      nonspecific defense against microbes entering the gastrointestinal tract,
      preparation of ions as well as liberation of protein-bound cobalamin and
      production of intrinsic factor for uptake further along the tract, and finally
      limited absorption of water, alcohol, and some fat-soluble food components
      including some drugs. These functions are influenced by various lifestyle
      factors, such as smoking and alcohol intake with interference by Helicobacter
      pylori colonization. This paper focuses on the interaction between lifestyle and
      gastric function.

PMID- 24732184
TI  - The psyche and gastric functions.
AB  - Although the idea that gastric problems are in some way related to mental
      activity dates back to the beginning of the last century, until now it has
      received scant attention by physiologists, general practitioners and
      gastroenterologists. The major breakthrough in understanding the interactions
      between the central nervous system and the gut was the discovery of the enteric
      nervous system (ENS) in the 19th century. ENS (also called 'little brain') plays
      a crucial role in the regulation of the physiological gut functions. Furthermore,
      the identification of corticotropin-releasing factor (CRF) and the development of
      specific CRF receptor antagonists have permitted to characterize the
      neurochemical basis of the stress response. The neurobiological response to
      stress in mammals involves three key mechanisms: (1) stress is perceived and
      processed by higher brain centers; (2) the brain mounts a neuroendocrine response
      by way of the hypothalamic-pituitary-adrenal axis (HPA) and the autonomic nervous
      system (ANS), and (3) the brain triggers feedback mechanisms by HPA and ANS
      stimulation to restore homeostasis. Various stressors such as anger, fear,
      painful stimuli, as well as life or social learning experiences affect both the
      individual's physiologic and gastric function, revealing a two-way interaction
      between brain and stomach. There is overwhelming experimental and clinical
      evidence that stress influences gastric function, thereby outlining the
      pathogenesis of gastric diseases such as functional dyspepsia, gastroesophageal
      reflux disease and peptic ulcer disease. A better understanding of the role of
      pathological stressors in the modulation of disease activity may have important
      pathogenetic and therapeutic implications.

PMID- 24732185
TI  - Epidemiological trends in stomach-related diseases.
AB  - Epidemiology is a study of disease variations by geography, population
      demographics and time. Temporal influences can manifest themselves as age
      effects, period effects, cohort effects, seasonal or monthly variations. The
      acquisition of Helicobacter pylori infection during early childhood and the
      ensuing risk for the future development of peptic ulcer or gastric cancer
      represents a typical example for a cohort effect in digestive diseases. The
      incidence and prevalence of uncomplicated peptic ulcer have decreased in recent
      years, largely because of the availability of treatment to eradicate H. pylori
      and the decreasing prevalence of H. pylori infection. Nowadays, gastric and
      duodenal ulcers tend to occur in older people, who were more likely to have been
      exposed to H. pylori in their childhood than recently born generations. The
      overall incidence of gastric cancers is declining; however, there has been a
      relative increase in the incidence of tumors of the esophagogastric junction and
      gastric cardia. Thus, by extrapolating the strong, stable and consistent
      mortality rate declines in recent decades, gastric cancer was projected to become
      increasingly less important as a cause of death in Europe in the next decades.

PMID- 24732186
TI  - The influence of cultural habits on the changing pattern of functional dyspepsia.
AB  - Dyspepsia is a common gastroenterological problem with an estimated global
      prevalence between 7 and 40%. Functional dyspepsia (FD) is a major economic
      burden to patients and healthcare systems and significantly affects patient
      quality of life. The ROME III definition of FD divides it into two subgroups,
      epigastric pain syndrome and postprandial distress syndrome, the former being
      more associated with reflux disease and the latter with gastric dysmotility. The
      global incidence and prevalence of FD continues to rise, but the reason for this
      is not clear. Rising global obesity and gastroesophageal reflux disease rates may
      be contributing to the rise in FD. Socioeconomic and cultural demographic changes
      such as changing dietary habits and rapid urbanization, particularly in the
      developing countries, are likely to be influencing the course of FD and the way
      it presents.

PMID- 24732187
TI  - Gastroduodenal mechanisms underlying functional gastric disorders.
AB  - Functional dyspepsia (FD), a disorder thought to originate from the
      gastroduodenum, is one of the most prevalent functional gastrointestinal
      disorders. In this review, we focused on gastroduodenal mechanisms involved in
      the pathophysiology of FD. The roles of impaired gastric accommodation, delayed
      gastric emptying, hypersensitivity to gastric distention and to luminal agents,
      altered mucosal integrity, low-grade inflammation and psychological stress are
      reviewed. The underlying pathophysiology in FD is probably multifactorial,
      involving a combination of several of these factors, ultimately leading to
      symptom pattern and severity.

PMID- 24732188
TI  - Therapeutic options for functional dyspepsia.
AB  - Functional dyspepsia (FD) is defined by the presence of chronic gastroduodenal
      symptoms in the absence of organic or systemic disease that explains them, and a
      negative upper endoscopy. According to the Rome III consensus, FD can be
      subdivided into PDS (postprandial distress syndrome) and EPS (epigastric pain
      syndrome). In patients with mild symptoms, reassurance and lifestyle adjustments
      are often sufficient. Pharmacotherapy, for those with more severe or persisting
      symptoms, includes the use of proton pump inhibitors (PPIs), prokinetics and
      psychotropic agents. In those diagnosed with Helicobacter pylori infection,
      eradication is recommended, although the symptom impact is often limited. PPIs
      are the initial therapy of choice for EPS, while prokinetics can be used in PDS.
      Tricyclic antidepressants can be used for refractory symptoms, especially in EPS.
      Emerging therapies include the novel gastroprokinetic agent acotiamide for PDS,
      fundus-relaxing 5-HT(1A) agonists in patients with PDS/early satiation and
      mirtazapine for FD with weight loss.

PMID- 24732189
TI  - Gastric barrier function and toxic damage.
AB  - Gastric epithelium is the first significant barrier between the inner body and
      the potentially toxic material in the lumen. Nutrients affect gastric barrier
      continuously--alcohol, coffee, spices, salted food, etc. Also, very potent
      noxious agents are widely prescribed drugs--nonsteroidal anti-inflammatory drugs
      (NSAIDs), aspirin and selective serotonin reuptake inhibitors. Helicobacter
      pylori is a well-known and well-investigated pathogen associated with serious
      gastric damage and gastric carcinoma. For its defense and maintenance of
      homeostasis and integrity, except acid secretion and maintenance of low luminal
      pH, gastric mucosa also has a specific structure, and its function is influenced
      by different control mechanisms. These include control of mucosal blood flow,
      control of mucus and bicarbonate secretion, constant cell renewal, and neuronal
      and hormonal control of defense mechanisms. These mechanisms are mediated by
      prostaglandins, nitric oxide, growth factors, heat-shock proteins and a
      neuropeptide called calcitonin gene-related protein. Adrenal glucocorticoids and
      the central nervous system also play an important role in regulating gastro
      protection, especially hypothalamus and the dorsal vagal complex. Gastric mucosa
      is also an important component of the body's immune system and gut-associated
      lymphoid tissue which serves as the initiation site for antigen-specific humoral
      and cell-mediated immune response. Treatment options for gastric barrier
      dysfunction and damage due to aforementioned noxious agents are guided by the
      nature of damage and our understanding of the pathophysiological mechanisms
      involved. Currently, management is guideline driven and depends upon eradication
      treatment in patients infected with H. pylori and treatment or prevention of
      aspirin or NSAID ulceration.

PMID- 24732190
TI  - Nutrients affecting gastric barrier.
AB  - The gastric barrier could be considered an active tissue involved in many
      synthetic and metabolic functions, as the immunological defense, by activating
      mucosal immune system. Barrier integrity results from a balance between
      protective and aggressive endogenous factors and from their interaction with
      exogenous factors (steroidal or nonsteroidal anti-inflammatory drugs, dietary
      nitrates, nitrites and/or NaCl, stress, Helicobacter pylori infection, food
      allergens and contaminants, metals, chemicals, radiation, smoking and alcohol
      intake). Nutrients represent the most important exogenous factors affecting
      gastric barrier because of the impact on people's everyday life. We report
      evidence from the literature about nutrients affecting gastric barrier and we
      investigate the possible effect that nutrients can play to determining or
      maintaining a gastric barrier dysfunction.

PMID- 24732191
TI  - Helicobacter pylori and gastric cancer.
AB  - Infection with Helicobacter pylori is established as the major risk factor for
      gastric cancer development. Damage of the mucosal barrier due to H. pylori
      induced inflammation enhances the carcinogenic effect of other risk factors such
      as salt intake or tobacco smoking. The genetic disposition of both the bacterial
      strain and the host can increase the potential towards gastric cancer formation.
      Genetic variance of the bacterial proteins CagA and VacA is associated with a
      higher gastric cancer risk, as are polymorphisms and epigenetic changes in host
      gene coding for interleukins (IL1beta, IL8), transcription factors (CDX2, RUNX3)
      and DNA repair enzymes. Application of high-throughput assays for genome-wide
      assessment of either genetic structural variance or gene expression patterns may
      lead to a better understanding of the pathobiological background of these
      processes, including the underlying signaling pathways. Understanding of the
      stepwise alterations that take place in the transition from chronic atrophic
      gastritis, via metaplastic changes, to invasive neoplasia is vital to define the
      'point of no return' before which eradication of H. pylori has the potential to
      prevent gastric cancer. Currently, eradication as preventive strategy is only
      recommended for high-incidence regions in Asia; large population studies with an
      adequate follow-up are required to demonstrate the effectiveness of such an
      approach in Western populations.

PMID- 24732192
TI  - Secondary prevention of epidemic gastric cancer in the model of Helicobacter
      pylori-associated gastritis.
AB  - Irrespective of its etiology, long-standing, non-self-limiting gastric
      inflammation (mostly in Helicobacter pylori-associated cases) is the
      cancerization ground on which epidemic (intestinal-type) gastric carcinoma (GC)
      can develop. The natural history of invasive gastric adenocarcinoma encompasses
      gastritis, atrophic mucosal changes, and intraepithelial neoplasia (IEN). The
      topography, the extent and the severity of the atrophic changes significantly
      correlate with the risk of developing both IEN and GC. In recent years, both
      noninvasive (serological) tests and invasive (endoscopy/biopsy) procedures have
      been proposed to stratify patients according to different classes of GC risk. As
      a consequence, different patient-tailored GC secondary prevention strategies have
      been put forward. This review summarizes the histological features of H. pylori
      related gastritis and the natural history of the disease. Histological and
      serological strategies to assess GC risk as well as the clinical management of
      atrophic gastritis patients are also discussed.

PMID- 24732193
TI  - Helicobacter pylori infection--management from a European perspective.
AB  - Since the first European Consensus Report on Helicobacter pylori management in
      1996 and the strong indication for therapy of peptic ulcer disease and other
      benign gastroduodenal pathologies, the list of indications for therapeutic
      interventions has been extended to selected extradigestive diseases. Test-and
      treat and search-and-treat strategies have been implemented for patients with
      dyspeptic symptoms and prevention of H. pylori-related complications (gastric
      cancer included), respectively. Screen and treat strategies are in discussion but
      are still lacking any structured implementation. For diagnosis of H. pylori,
      accurate noninvasive and endoscopy-based tests are widely available across
      Europe, and individual tests are selected according to patient needs and clinical
      settings. Standard proton pump inhibitor-based triple therapy faces increasing
      failure rates mainly because of clarithromycin resistance, but alternative first
      line options bismuth quadruple, or non-bismuth quadruples in various combinations
      have emerged as effective first-line alternatives. After treatment failure,
      defined rescue therapies including individual antibiotic-sensitive testing are
      recommended.

PMID- 24732194
TI  - Clinical management of Helicobacter pylori--the Japanese perspective.
AB  - BACKGROUND: After the approval of health insurance coverage of eradication
      therapy for Helicobacter pylori-positive peptic ulcer disease (PUD) in 2000,
      comprehensive coverage for H. pylori infection itself was implemented in 2013.
      METHODS: We did a literature search using PubMed database on the management of H.
      pylori infection including indications, regimens, outcomes of current eradication
      therapies, trends of antibiotic resistance rates and proposed third-line rescue
      therapy in Japan. We also collected data on changes of eradication rates in our
      hospital by searching electronic medical records. RESULTS: After implementation
      of insurance coverage of eradication therapy for PUD, dramatic reduction of the
      number patients with PUD as well as spending on ulcer drug was documented.
      According to the current regulation, proton pump inhibitor (PPI)-based triple
      therapy with 2 antibiotics, amoxicillin (AMPC) plus clarithromycin, for 7 days is
      approved as the first-line therapy. After failure of the first-line therapy, PPI
      plus AMPC and metronidazole is authorized as the second line, which maintains an
      excellent eradication rate of over 90% in Japan. When these two therapies fail, a
      sitafloxacin-based therapy seems to be most promising among many rescue regimens.
      CONCLUSION: Comprehensive public health insurance coverage of H. pylori infection
      will promote eradication in Japanese people infected with H. pylori, whose risk
      of developing gastric cancer has been shown to be high. It also provides us a
      unique opportunity to study whether the broader indications can accelerate the
      reduction of gastric cancer in Japan in the same way we witnessed the reduction
      of PUD.

PMID- 24732195
TI  - The Korean perspective of Helicobacter pylori infection: lessons from the
      Japanese government's policy to prevent gastric cancer.
AB  - The guideline of the Korean College of Helicobacter and Upper Gastrointestinal
      Research group for Helicobacter pylori infection was first produced in 1998, when
      definite indication for H. pylori eradication is early gastric cancer in addition
      to the previous indications of peptic ulcer (PUD) including scar lesion and
      marginal zone B cell lymphoma (MALT type). Though treatment is recommended for
      the relatives of a patient with gastric cancer, unexplained iron deficiency
      anemia, and chronic idiopathic thrombocytopenic purpura, a consensus treatment
      guideline is the treatment of PUD, MALToma, and gastric cancer in Korea. One- or
      2-week treatment with proton pump inhibitor (PPI)-based triple therapy consisting
      of one PPI and 2 antibiotics, clarithromycin and amoxicillin, is recommended as
      the first-line treatment regimen. In the case of treatment failure, one or 2
      weeks of quadruple therapy (PPI + metronidazole + tetracycline + bismuth) is
      recommended, whose eradication regimen was not different between Korea and Japan.
      Though the treatment regimen was similar between two nations, the Japanese
      government declared the inclusion of H. pylori eradication in patients with H.
      pylori-associated chronic gastritis, reaching the conclusion that the treatment
      guideline became quite different between Korea and Japan from February 21, 2013.
      The prime rationale of the Japanese extended treatment guideline for H. pylori
      infection was based on the drastic intention to prevent gastric cancer as well as
      the improvement of chronic gastritis-associated functional dyspepsia based on
      their findings that H. pylori eradication might decrease gastric cancer incidence
      as well as mortality. In this review, the discrepancy between the Korean and
      Japanese treatment guidelines will be explained; why and how?

PMID- 24732196
TI  - Management of Helicobacter pylori-related diseases in the Baltic States.
AB  - Helicobacter pylori infection has been recognized as the main trigger of stomach
      related diseases. The huge variation in H. pylori infection patterns across the
      globe requires targeted research and close monitoring of this infection in
      different regions. The Baltic countries have witnessed enormous changes in
      socioeconomic conditions in the last years. Evolution of H. pylori infection and
      related diseases has been a key interest of gastroenterology centers in the
      Baltic States over the last two decades, translating into up-to-date scientific
      data that are valuable locally and on the European level. The East-West gradient
      in the prevalence of H. pylori infection is still evident in the Baltic
      countries, but the gap is becoming smaller, and similar trends are expected for
      the coming years. Clarithromycin-based triple therapy remains the first-line
      treatment of H. pylori in the region; however, careful monitoring of resistance
      rates in the future remains highly relevant, though routine resistance testing is
      not available in all the countries. A high prevalence of gastric cancer is still
      notable in the Baltic States; nevertheless, a steady decline in gastric cancer
      incidence in Lithuania, Latvia and Estonia is present and expected to be
      continuing during the coming decades. Currently, H. pylori-related diseases still
      constitute a substantial part of gastroenterologists' workload in the region.
      This paper reviews epidemiological, diagnostic, treatment as well as basic
      research trends on H. pylori infection and related diseases in the Baltic States
      during the last two decades.

PMID- 24732197
TI  - Clinical management of Helicobacter pylori: the Latin American perspective.
AB  - In most South American countries, Helicobacter pylori infection prevalence is
      high, affecting over 70% in populations with precarious living conditions. It is
      worth pointing out that there is initial evidence of a decline in prevalence of
      H. pylori infection at least in some more privileged fragments of the population.
      It is estimated that gastric cancer, the main clinical sequela of H. pylori
      infection, has an average incidence rate of 12.4 cases per 100,000 inhabitants
      (8.4 cases per 100,000 inhabitants for women and 17.3 cases per 100,000 for men)
      in the region. Classical triple therapy [proton pump inhibitor (PPI), amoxicillin
      and clarithromycin] is still the most used regimen with eradication rates around
      80%. The rates of resistance to clarithromycin range from 2 to 24%. Recurrence
      rates of the infection are described as 2.9% in Argentina, 4.2% in Chile, 2-7% in
      Brazil, and 11.5% in a trial involving 7 Latin American countries. After failure
      of clarithromycin-containing regimens, second- and third-line therapies using
      PPI, amoxicillin and levofloxacin and quadruple therapy with PPI, colloidal
      bismuth subcitrate, tetracycline hydrochloride and metronidazole are recommended.
      Due to the high rates of primary resistance to metronidazole in the Latin
      American countries, use of the quadruple therapy, replacing metronidazole for
      furazolidone, is a frequent option. Rescue triple therapy regimens using
      furazolidone in association with levofloxacin and PPI have also been used. Most
      recommended rescue therapies reach eradication rates close to 80%.

PMID- 24732198
TI  - Retraction statement. Paper by Cucchiara S, Iebba V, Conte MP, Schippa S:
      Digestive Diseases 2009;27:252-258 (DOI: 10.1159/000228558).

PMID- 24732199
TI  - Retraction statement. Paper by Iebba V, Aloi M, Civitelli F, Cucchiara S:
      Digestive Diseases 2011;29:531-539 (DOI: 10.1159/000332969).

PMID- 24732200
TI  - Retraction statement. Paper by Krznaric Z, Vranesic Bender D, Kunovic A, Kekez D,
      Stimac D: Digestive Diseases 2012;30:196-200 (DOI: 10.1159/000336965).

PMID- 24732201
TI  - Response to commentary: Post-Vietnam military herbicide exposures in UC-123 Agent
      Orange spray aircraft.

PMID- 24732202
TI  - Commentary on "Post-Vietnam military herbicide exposures in UC-123 Agent Orange
      spray aircraft".

PMID- 24732204
TI  - An N-terminal fragment of yeast ribosomal protein L3 inhibits the cytotoxicity of
      pokeweed antiviral protein in Saccharomyces cerevisiae.
AB  - We have previously shown that ribosomal protein L3 is required for pokeweed
      antiviral protein (PAP), a type I ribosome inactivating protein, to bind to
      ribosomes and depurinate the alpha-sarcin/ricin loop (SRL) in yeast. Co
      expression of the N-terminal 99 amino acids of yeast L3 (L3Delta99) with PAP in
      transgenic tobacco plants completely abolished the toxicity of PAP. In this
      study, we investigated the interaction between PAP and L3Delta99 in Saccharomyces
      cerevisiae. Yeast cells co-transformed with PAP and L3Delta99 showed markedly
      reduced growth inhibition and reduced rRNA depurination by PAP, compared to cells
      transformed with PAP alone. Co-transformation of yeast with PAP and L3Delta21
      corresponding to the highly conserved N-terminal 21 amino acids of L3Delta99,
      reduced the cytotoxicity of PAP. PAP mRNA and protein levels were elevated and
      L3Delta99 or L3Delta21 mRNA and protein levels were reduced in yeast co
      transformed with PAP and L3Delta99 or with PAP and L3Delta21, respectively. PAP
      interacted with L3Delta21 in yeast cells in vivo and by Biacore analysis in
      vitro, suggesting that the interaction between L3Delta21 and PAP may inhibit PAP
      mediated depurination of the SRL, leading to a reduction in the cytotoxicity of
      PAP. 

PMID- 24732205
TI  - Comment on Hurley, J.C. Towards clinical application of anti-endotoxin
      antibodies; a re-appraisal of the disconnect. Toxins 2013, 5, 2589-2620.

PMID- 24732206
TI  - Response to John G. Brock-Utne. Comment on Hurley, J.C. Towards clinical
      application of anti-endotoxin antibodies; a re-appraisal of the disconnect.

PMID- 24732203
TI  - Recent developments in antibody-based assays for the detection of bacterial
      toxins.
AB  - Considering the urgent demand for rapid and accurate determination of bacterial
      toxins and the recent promising developments in nanotechnology and microfluidics,
      this review summarizes new achievements of the past five years. Firstly,
      bacterial toxins will be categorized according to their antibody binding
      properties into low and high molecular weight compounds. Secondly, the types of
      antibodies and new techniques for producing antibodies are discussed, including
      poly- and mono-clonal antibodies, single-chain variable fragments (scFv), as well
      as heavy-chain and recombinant antibodies. Thirdly, the use of different
      nanomaterials, such as gold nanoparticles (AuNPs), magnetic nanoparticles (MNPs),
      quantum dots (QDs) and carbon nanomaterials (graphene and carbon nanotube), for
      labeling antibodies and toxins or for readout techniques will be summarized.
      Fourthly, microscale analysis or minimized devices, for example microfluidics or
      lab-on-a-chip (LOC), which have attracted increasing attention in combination
      with immunoassays for the robust detection or point-of-care testing (POCT), will
      be reviewed. Finally, some new materials and analytical strategies, which might
      be promising for analyzing toxins in the near future, will be shortly introduced.

PMID- 24732207
TI  - Developmental processes regulated by the 3-hydroxy-3-methylglutaryl-CoA reductase
      (HMGCR) pathway: highlights from animal studies.
AB  - The 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR) is the rate-limiting
      enzyme in the biosynthesis of cholesterol and isoprenoids, which are substrates
      required for post-translational modification of signalling proteins that can
      potentially regulate various aspects of embryonic development. The HMGCR
      transcripts are detectable during early embryogenesis in both invertebrates and
      vertebrates, which suggests a conserved developmental requirement for mevalonate
      derivatives. Consistently, recent animal and in vitro studies have yielded
      valuable insights into potential morphogenic parameters that are modulated by
      HMGCR activity. These developmental end-points include brain and craniofacial
      morphogenesis, PGC migration and survival, myocardial epithelial migration and
      fusion, EC migration and survival, and vascular stabilization. By providing a
      synthesis of these studies, we hope that this review will highlight the need to
      comprehensively examine the entire suite of developmental processes regulated by
      HMGCR. 

PMID- 24732208
TI  - The impact of blood pressure on kidney function in the elderly: a cross-sectional
      study.
AB  - BACKGROUND/AIMS: Intensive blood pressure (BP) target decreases blood perfusion
      of kidneys that attenuates the benefits of BP treatment in elderly hypertensive
      individuals. The optimal BP goal for renal function in the hypertensive elderly
      has been unclear. We investigated the impact of BP on renal function to define
      the appropriate BP target in the elderly. METHODS: A total of 28,258 elderly
      subjects were categorized into normotensive (Norm), hypotensive (Hypo) and
      hypertensive (Hyper) groups according to BP levels. Systolic, diastolic and pulse
      BP (SBP, DBP and PBP) were further stratified by 10 mmHg. Blood urea nitrogen,
      serum creatinine, uric acid, glomerular filtration rate (GFR), renal
      insufficiency prevalence (RIP) and proteinuria prevalence (PP) were compared
      among different groups and BP strata. The RIP and PP in the elderly with obesity,
      hyperlipidemia or diabetes in Norm, Hypo and Hyper groups were evaluated.
      RESULTS: GFR in Hypo and Hyper groups was significantly lower than that in Norm
      group. The RIP and PP was higher in Hypo and Hyper groups than that in the Norm
      group. Proteinuria became more prevalent when SBP was >140 mmHg or <90 mmHg.
      DBP>80 mmHg increased PP while DBP<70 mmHg increased RIP. PBP>60 mmHg led to an
      increased RIP and PP. Obesity or hyperlipidemia only combined with hypertension
      caused a significantly increased RIP and PP. Diabetes independent of hypertension
      contributed to higher RIP and PP. CONCLUSIONS: The most beneficial BP target for
      kidney function in the elderly may be SBP of 90-140 mmHg and DBP of 70-80 mmHg.
      PBP <60 mmHg may be appropriate.

PMID- 24732209
TI  - Complement factor I polymorphism is not associated with neovascular age-related
      macular degeneration and polypoidal choroidal vasculopathy in a chinese
      population.
AB  - PURPOSE: To identify the associations of the two complement factor I (CFI)
      polymorphisms rs10033900 and rs2285714 with risk of neovascular age-related
      macular degeneration (nAMD) and polypoidal choroidal vasculopathy (PCV) in a
      Chinese case-control study. METHODS: A total of 900 subjects - 300 controls, 300
      cases with nAMD and 300 cases with PCV - were included in the present study.
      Genomic DNA was extracted from venous blood leukocytes. The allelic variants of
      rs10033900 and rs2285714 were determined by matrix-assisted laser
      desorption/ionization time-of-flight mass spectrometry. The differences in allele
      distribution between the cases and controls were tested by a chi(2) test with age
      and gender adjusted for by logistic regression analysis. We also performed a meta
      analysis of the case-control studies of rs10033900 and rs2285714 based on the
      currently available evidence from the literature. The meta-analysis was conducted
      via an inverse-variance, fixed-effects model, as previously described. RESULTS:
      No statistically significant association was observed between the two
      polymorphisms of CFI and AMD risk, including nAMD, PCV and combined AMD (p > 0.05
      for all comparisons). By meta-analysis, we detected significant associations
      between both of the SNPs and late AMD, which is consistent with previous results
      (odds ratio, OR, rs10033900 = 0.814, p rs10033900 < 0.001; OR rs2285714 = 1.221,
      p rs2285714 < 0.001). For rs2285714, the results of the meta-analysis were less
      reliable due to its heterogeneity. CONCLUSIONS: In our case-control study,
      neither of the two SNPs most studied (rs10033900 or rs2285714) in the CFI gene
      was a risk factor for developing nAMD or PCV in a Chinese population. Additional
      large, comprehensive and well-designed association studies are needed to better
      understand the role of ethnicity and other gene interactions in the association
      between the CFI gene and AMD.

PMID- 24732210
TI  - Monitoring daily MLC positional errors using trajectory log files and EPID
      measurements for IMRT and VMAT deliveries.
AB  - This work investigated the differences between multileaf collimator (MLC)
      positioning accuracy determined using either log files or electronic portal
      imaging devices (EPID) and then assessed the possibility of reducing patient
      specific quality control (QC) via phantom-less methodologies. In-house software
      was developed, and validated, to track MLC positional accuracy with the
      rotational and static gantry picket fence tests using an integrated electronic
      portal image. This software was used to monitor MLC daily performance over a 1
      year period for two Varian TrueBeam linear accelerators, with the results
      directly compared with MLC positions determined using leaf trajectory log files.
      This software was validated by introducing known shifts and collimator errors.
      Skewness of the MLCs was found to be 0.03 +/- 0.06 degrees  (mean +/-1 standard
      deviation (SD)) and was dependent on whether the collimator was rotated manually
      or automatically. Trajectory log files, analysed using in-house software, showed
      average MLC positioning errors with a magnitude of 0.004 +/- 0.003 mm
      (rotational) and 0.004 +/- 0.011 mm (static) across two TrueBeam units over 1
      year (mean +/-1 SD). These ranges, as indicated by the SD, were lower than the
      related average MLC positioning errors of 0.000 +/- 0.025 mm (rotational) and
      0.000 +/- 0.039 mm (static) that were obtained using the in-house EPID based
      software. The range of EPID measured MLC positional errors was larger due to the
      inherent uncertainties of the procedure. Over the duration of the study, multiple
      MLC positional errors were detected using the EPID based software but these same
      errors were not detected using the trajectory log files. This work shows the
      importance of increasing linac specific QC when phantom-less methodologies, such
      as the use of log files, are used to reduce patient specific QC. Tolerances of
      0.25 mm have been created for the MLC positional errors using the EPID-based
      automated picket fence test. The software allows diagnosis of any specific leaf
      that needs repair and gives an indication as to the course of action that is
      required. 

PMID- 24732211
TI  - Toward understanding the dynamics of microbial communities in an estuarine
      system.
AB  - Community assembly theories such as species sorting theory provide a framework
      for understanding the structures and dynamics of local communities. The effect of
      theoretical mechanisms can vary with the scales of observation and effects of
      specific environmental factors. Based on 16S rRNA gene tag pyrosequencing,
      different structures and temporal succession patterns were discovered between the
      surface sediments and bottom water microbial communities in the Pearl River
      Estuary (PRE). The microbial communities in the surface sediment samples were
      more diverse than those in the bottom water samples, and several genera were
      specific for the water or sediment communities. Moreover, water temperature was
      identified as the main variable driving community dynamics and the microbial
      communities in the sediment showed a greater temporal change. We speculate that
      nutrient-based species sorting and bacterial plasticity to the temperature
      contribute to the variations observed between sediment and water communities in
      the PRE. This study provides a more comprehensive understanding of the microbial
      community structures in a highly dynamic estuarine system and sheds light on the
      applicability of ecological theoretical mechanisms. 

PMID- 24732212
TI  - Oleanolic acid modulates the immune-inflammatory response in mice with
      experimental autoimmune myocarditis and protects from cardiac injury. Therapeutic
      implications for the human disease.
AB  - Myocarditis and dilated cardiomyopathy (DCM) are inflammatory diseases of the
      myocardium, for which appropriate treatment remains a major clinical challenge.
      Oleanolic acid (OA), a natural triterpene widely distributed in food and
      medicinal plants, possesses a large range of biological effects with beneficial
      properties for health and disease prevention. Several experimental approaches
      have shown its cardioprotective actions, and OA has recently been proven
      effective for treating Th1 cell-mediated inflammatory diseases; however, its
      effect on inflammatory heart disorders, including myocarditis, has not yet been
      addressed. Therefore, the present study was undertaken to determine the
      effectiveness of OA in prevention and treatment of experimental autoimmune
      myocarditis (EAM). The utility of OA was evaluated in vivo through their
      administration to cardiac alpha-myosin (MyHc-alpha614-629)-immunized BALB/c mice
      from day 0 or day 21 post-immunization to the end of the experiment, and in vitro
      through their addition to stimulated-cardiac cells. Prophylactic and therapeutic
      administration of OA dramatically decreased disease severity: the heart
      weight/body weight ratio as well as plasma levels of brain natriuretic peptide
      and myosin-specific autoantibodies production were significantly reduced in OA
      treated EAM animals, compared with untreated ones. Histological heart analysis
      showed that OA-treatment diminished cell infiltration, fibrosis and dystrophic
      calcifications. OA also decreased proliferation of cardiac fibroblast in vitro
      and attenuated calcium and collagen deposition induced by relevant cytokines of
      active myocarditis. Furthermore, in OA-treated EAM mice the number of Treg cells
      and the production of IL-10 and IL-35 were markedly increased, while
      proinflammatory and profibrotic cytokines were significantly reduced. We
      demonstrate that OA ameliorates both developing and established EAM by promoting
      an antiinflammatory cytokine profile and by interfering with the generation of
      cardiac-specific autoantibodies, as well as through direct protective effects on
      cardiac cells. Therefore, we envision this natural product as novel helpful tool
      for intervention in inflammatory cardiomyopathies including myocarditis. 

PMID- 24732213
TI  - The art of the deal in myofilament modulation of function.

PMID- 24732214
TI  - An interference-free two-step enzyme assay with UPLC-tandem mass spectrometric
      product measurement for the clinical diagnosis of uridine diphosphate galactose-4
      epimerase deficiency.
AB  - We present a robust clinical assay for the measurement of red blood cell uridine
      diphosphate galactose-4-epimerase enzyme activity for the diagnostic confirmation
      of patients positive for a newborn screen for inherited galactosemia in whom
      galactose-1-phosphate uridyltransferase activity is normal. Previous assays
      required the use of ion-pairing reagents and frequent need for system maintenance
      that was not appropriate for heavy clinical use where patient results should be
      quickly available. We have designed a two-step enzyme assay which converts stable
      isotope-labeled UDP-galactose to isotope-labeled-UDP-glucose which is converted
      in the second reaction to the final product of [(13)C6]-UDP-glucuronic acid.
      Measurement conditions t remove potential interference from endogenous UDP
      glucose and UDP-galactose. We also report a significant ion suppression effect of
      the red cell preparation for which we have optimized assay sample volume to
      minimize this effect. 

PMID- 24732215
TI  - Development of LC-MS determination method and back-propagation ANN
      pharmacokinetic model of corynoxeine in rat.
AB  - Corynoxeine(CX), isolated from the extract of Uncaria rhynchophylla, is a useful
      and prospective compound in the prevention and treatment for vascular diseases. A
      simple and selective liquid chromatography mass spectrometry (LC-MS) method was
      developed to determine the concentration of CX in rat plasma. The chromatographic
      separation was achieved on a Zorbax SB-C18 (2.1 mm * 150 mm, 5 MUm) column with
      acetonitrile-0.1% formic acid in water as mobile phase. Selective ion monitoring
      (SIM) mode was used for quantification using target ions m/z 383 for CX and m/z
      237 for the carbamazepine (IS). After the LC-MS method was validated, it was
      applied to a back-propagation artificial neural network (BP-ANN) pharmacokinetic
      model study of CX in rats. The results showed that after intravenous
      administration of CX, it was mainly distributed in blood and eliminated quickly,
      t1/2 was less than 1h. The predicted concentrations generated by BP-ANN model had
      a high correlation coefficient (R>0.99) with experimental values. The developed
      BP-ANN pharmacokinetic model can be used to predict the concentration of CX in
      rats.

PMID- 24732216
TI  - Want to be a camp nurse? Ten basics to get you out there!

PMID- 24732217
TI  - Family caregivers: adjust or bust.

PMID- 24732218
TI  - Reduce falls through tests of change.

PMID- 24732220
TI  - Helping patients leave a legacy.

PMID- 24732222
TI  - Life is a circus: find your balance.

PMID- 24732226
TI  - Strike gold when interviewing for your first nursing job.

PMID- 24732227
TI  - My heart belongs in Haiti.

PMID- 24732228
TI  - Patient- and family-centered care: not just for kids.

PMID- 24732229
TI  - Caring for the caregiver.

PMID- 24732230
TI  - Does a novel method of PICC insertion improve safety?
AB  - BACKGROUND: Placing a central venous access device via the internal jugular or
      subclavian vein entails significant risks to both patient and healthcare worker.
      PURPOSE: The purpose of this randomized, prospective study was to determine
      whether the accelerated Seldinger technique (AST) offers significant safety
      advantages over the modified Seldinger technique (MST) for peripherally inserted
      central catheter insertion. MATERIALS AND METHODS: Patients were randomly
      assigned to undergo introducer sheath insertion by means of either MST or AST.
      Primary outcome measures included time to completion of introducer sheath
      insertion, estimated blood loss, and success rate. Secondary outcome measures
      included vessel-to-air exposure events and unprotected sharps exposure.
      DISCUSSION: While both insertion methods proved equivalent for successful vessel
      cannulation, AST was significantly faster (P = 0.0048) and resulted in less blood
      loss (P = 0.0295) than MST. Additionally, AST resulted in significantly fewer
      vessel-to-air exposure events (P < 0.0001) and unprotected sharps exposures (P <
      0.0001). Although this was a relatively small and unblinded study, the high
      degree of statistical significance of the study results suggests that, for both
      patients and healthcare workers, AST is faster and safer than MST for PICC
      peelable introducer sheath insertion.

PMID- 24732231
TI  - Nanoscale silver for infection control.

PMID- 24732233
TI  - Multi drug resistant tuberculosis in Mosango, a rural area in the Democratic
      Republic of Congo.
AB  - Multidrug Resistant Tuberculosis (MDR-TB) is a serious threat which jeopardizes
      the worldwide efforts to control TB. The Democratic Republic of Congo (DRC) is
      one of 27 countries with a high burden of MDR-TB. Data on the magnitude, trends,
      and the distribution of MDR-TB in DRC are scanty. Kinshasa, the capital city of
      DRC which accounts for 20% of all TB cases nationwide, is notifying more than 80%
      of all MDR suspects. We report here a cluster of MDR-TB cases that was
      investigated in the Mosango health district, in the Bandundu south Province, DRC
      in 2008. Phenotypic Drug Sensitivity Testing and DNA sequencing were performed on
      18 sputum specimens collected from 4 MDR-TB suspects and 5 household contacts.
      Sequencing data confirmed that the 4 suspects were indeed Rifampicin resistant
      cases. Sequencing of the rpoB gene showed that 3 cases (patients A, B and D) had
      a single mutation encoding a substitution to 526Tyr, 531Trp and 526Leu
      respectively. Patient C had a double mutation encoding a change to 531Leu and
      633Leu. Two of the investigated cases died within 4 months of a second-line
      treatment course. Results highlight the need to enhance adequate laboratory
      services within the country for both clinical as well as surveillance purposes. 

PMID- 24732234
TI  - Awareness of kidney disease among US adults: Findings from the 2011 behavioral
      risk factor surveillance system.
AB  - BACKGROUND: The prevalence of chronic kidney disease as measured by biomarkers is
      increasing, but the recognition for this condition remains low in the USA. Little
      is known about the awareness of kidney disease at the state level. METHODS: Data
      from 490,302 adults aged 18 years or older in all 50 states as well as the
      District of Columbia who participated in the 2011 Behavioral Risk Factor
      Surveillance System were analyzed. Kidney disease diagnosis, a measure of
      individual awareness, was ascertained by participants' self-report in the
      telephone survey. Prevalence ratios of self-reported kidney disease in
      subpopulations were estimated and tested using log-linear regression analyses
      with a robust variance estimator. RESULTS: The unadjusted prevalence of self
      reported kidney disease was estimated to be 2.5%. After adjustment for age and
      all other selected covariates, Hispanics had a higher prevalence than non
      Hispanic whites (adjusted prevalence ratio 1.2, 95% CI 1.0-1.4). Persons who were
      unemployed (adjusted prevalence ratio 1.4, 95% CI 1.2-1.5) had a higher
      prevalence than those who were employed. Persons who had hypertension (adjusted
      prevalence ratio 1.9, 95% CI 1.7-2.1), diabetes (adjusted prevalence ratio 1.7,
      95% CI 1.5-1.8), cardiovascular disease (coronary heart disease, myocardial
      infarction or stroke; adjusted prevalence ratio 1.5, 95% CI 1.4-1.6) or cancer
      (adjusted prevalence ratio 1.5, 95% CI 1.3-1.6) had a higher prevalence of self
      reported kidney disease than those without these conditions. CONCLUSION: The
      overall awareness of kidney disease was low in the general population. Efforts
      are needed to promote the awareness and early detection of kidney disease in
      public health services and clinical practice.

PMID- 24732236
TI  - Stochastic nonlinear time series forecasting using time-delay reservoir
      computers: performance and universality.
AB  - Reservoir computing is a recently introduced machine learning paradigm that has
      already shown excellent performances in the processing of empirical data. We
      study a particular kind of reservoir computers called time-delay reservoirs that
      are constructed out of the sampling of the solution of a time-delay differential
      equation and show their good performance in the forecasting of the conditional
      covariances associated to multivariate discrete-time nonlinear stochastic
      processes of VEC-GARCH type as well as in the prediction of factual daily market
      realized volatilities computed with intraday quotes, using as training input
      daily log-return series of moderate size. We tackle some problems associated to
      the lack of task-universality for individually operating reservoirs and propose a
      solution based on the use of parallel arrays of time-delay reservoirs. 

PMID- 24732237
TI  - Model, analysis, and evaluation of the effects of analog VLSI arithmetic on
      linear subspace-based image recognition.
AB  - Typical image recognition systems operate in two stages: feature extraction to
      reduce the dimensionality of the input space, and classification based on the
      extracted features. Analog Very Large Scale Integration (VLSI) is an attractive
      technology to achieve compact and low-power implementations of these
      computationally intensive tasks for portable embedded devices. However, device
      mismatch limits the resolution of the circuits fabricated with this technology.
      Traditional layout techniques to reduce the mismatch aim to increase the
      resolution at the transistor level, without considering the intended application.
      Relating mismatch parameters to specific effects in the application level would
      allow designers to apply focalized mismatch compensation techniques according to
      predefined performance/cost tradeoffs. This paper models, analyzes, and evaluates
      the effects of mismatched analog arithmetic in both feature extraction and
      classification circuits. For the feature extraction, we propose analog adaptive
      linear combiners with on-chip learning for both Least Mean Square (LMS) and
      Generalized Hebbian Algorithm (GHA). Using mathematical abstractions of analog
      circuits, we identify mismatch parameters that are naturally compensated during
      the learning process, and propose cost-effective guidelines to reduce the effect
      of the rest. For the classification, we derive analog models for the circuits
      necessary to implement Nearest Neighbor (NN) approach and Radial Basis Function
      (RBF) networks, and use them to emulate analog classifiers with standard
      databases of face and hand-writing digits. Formal analysis and experiments show
      how we can exploit adaptive structures and properties of the input space to
      compensate the effects of device mismatch at the application level, thus reducing
      the design overhead of traditional layout techniques. Results are also directly
      extensible to multiple application domains using linear subspace methods. 

PMID- 24732235
TI  - Compartments within a compartment: what C. elegans can tell us about ciliary
      subdomain composition, biogenesis, function, and disease.
AB  - The primary cilium has emerged as a hotbed of sensory and developmental
      signaling, serving as a privileged domain to concentrate the functions of a wide
      number of channels, receptors and downstream signal transducers. This realization
      has provided important insight into the pathophysiological mechanisms underlying
      the ciliopathies, an ever expanding spectrum of multi-symptomatic disorders
      affecting the development and maintenance of multiple tissues and organs. One
      emerging research focus is the subcompartmentalised nature of the organelle,
      consisting of discrete structural and functional subdomains such as the
      periciliary membrane/basal body compartment, the transition zone, the Inv
      compartment and the distal segment/ciliary tip region. Numerous ciliopathy,
      transport-related and signaling molecules localize at these compartments,
      indicating specific roles at these subciliary sites. Here, by focusing
      predominantly on research from the genetically tractable nematode C. elegans, we
      review ciliary subcompartments in terms of their structure, function,
      composition, biogenesis and relationship to human disease. 

PMID- 24732238
TI  - Depletion of natural killer cells increases mice susceptibility in a Pseudomonas
      aeruginosa pneumonia model.
AB  - OBJECTIVES: Pseudomonas aeruginosa infection is a clinically relevant infection
      involved in pneumonia in ICUs. Understanding the type of immune response
      initiated by the host during pneumonia would help defining new strategies to
      interfere with the bacteria pathogenicity. In this setting, the role of natural
      killer cells remains controversial. We assessed the role of systemic natural
      killer cells in a Pseudomonas aeruginosa mouse pneumonia model. DESIGN:
      Experimental study. SETTING: Research laboratory from a university hospital.
      SUBJECTS: RjOrl:SWISS and BALB/cJ mice (weight, 20-24 g). INTERVENTIONS: Lung
      injuries were assessed by bacterial load, myeloperoxidase activity, endothelial
      permeability (pulmonary edema), immune cell infiltrate (histological analysis),
      proinflammatory cytokine release, and Ly6-G immunohistochemistry. Bacterial loads
      were assessed in the lungs and spleen. Natural killer cell number and status were
      assessed in spleen (flow cytometry and quantitative polymerase chain reaction).
      Depletion of natural killer cells was achieved through an IV anti-asialo-GM1
      antibody injection. MEASUREMENTS AND MAIN RESULTS: Pseudomonas aeruginosa
      tracheal instillation led to an acute pneumonia with a rapid decrease of
      bacterial load in lungs and with an increase of endothelial permeability,
      proinflammatory cytokines (tumor necrosis factor-alpha and interleukin-1beta),
      and myeloperoxidase activity followed by Ly6-G positive cell infiltrate in lungs.
      Pseudomonas aeruginosa was detected in the spleen. Membrane markers of activation
      and maturation (CD69 and KLRG1 molecules) were increased in splenic natural
      killer cells during Pseudomonas aeruginosa infection. Splenic natural killer
      cells activated upon Pseudomonas aeruginosa infection produced interferon-gamma
      but not interleukin-10. Ultimately, mice depleted of natural killer cells
      displayed an increased neutrophil numbers in the lungs and an increased mortality
      rate without bacterial load modifications in the lungs, indicating that mice
      depleted of natural killer cells were much more susceptible to infection compared
      with control animals. CONCLUSIONS: We report for the first time that natural
      killer cells play a major role in the mice susceptibility toward a Pseudomonas
      aeruginosa-induced acute pneumonia model.

PMID- 24732240
TI  - Long-term survival in patients with severe acute respiratory distress syndrome
      and rescue therapies for refractory hypoxemia*.
AB  - OBJECTIVES: To describe long-term survival in patients with severe acute
      respiratory distress syndrome and assess differences in patient characteristics
      and outcomes among those who receive rescue therapies (prone position
      ventilation, inhaled nitric oxide, or inhaled epoprostenol) versus conventional
      treatment. DESIGN: Cohort study of patients with severe hypoxemia. SETTING:
      University-affiliated level 1 trauma center. PATIENTS: Patients diagnosed with
      severe acute respiratory distress syndrome within 72 hours of ICU admission
      between January 1, 2008, and December 31, 2011. INTERVENTIONS: None. MEASUREMENTS
      AND MAIN RESULTS: Data were abstracted from the medical record and included
      demographic and clinical variables, hospital and ICU length of stay, discharge
      disposition, and hospital costs. Patient-level data were linked to the Washington
      State Death Registry. Kaplan-Meier methods and Cox's proportional hazards models
      were used to estimate survival and hazard ratios. Four hundred twenty-eight
      patients meeting study inclusion criteria were identified; 62 (14%) were
      initiated on a rescue therapy. PaO2/FIO2 ratios were comparable at admission
      between patients treated with a rescue therapy and those treated conventionally
      but were substantially lower by 72 hours in those who received rescue therapies
      (54 +/- 17 vs 69 +/- 17 mm Hg; p < 0.01). For the entire cohort, estimated
      survival probability at 3 years was 55% (95% CI, 51-61%). Among 280 hospital
      survivors (65%), 3-year survival was 85% (95% CI, 80-89%). The relative hazard of
      in-hospital mortality was 68% higher among patients who received rescue therapy
      compared with patients treated conventionally (95% CI, 8-162%; p = 0.02). For
      long-term survival, the hazard ratio of death following ICU admission was 1.56
      (95% CI, 1.02-2.37; p = 0.04), comparing rescue versus conventional treatment.
      CONCLUSIONS: Despite high hospital mortality, severe acute respiratory distress
      syndrome patients surviving to hospital discharge have relatively good long-term
      survival. Worsening hypoxemia was associated with initiation of rescue therapy.
      Patients on rescue therapy had higher in-hospital mortality; however, survivors
      to hospital discharge had long-term survival that was comparable to other acute
      respiratory distress syndrome survivors.

PMID- 24732239
TI  - Improved prognosis of septic shock in patients with cirrhosis: a multicenter
      study*.
AB  - OBJECTIVE: To determine the evolution of the outcome of patients with cirrhosis
      and septic shock. DESIGN: A 13-year (1998-2010) multicenter retrospective cohort
      study of prospectively collected data. SETTING: The College des Utilisateurs des
      Bases des donnees en Reanimation (CUB-Rea) database recording data related to
      admissions in 32 ICUs in Paris area. PATIENTS: Thirty-one thousand two hundred
      fifty-one patients with septic shock were analyzed; 2,383 (7.6%) had cirrhosis.
      INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Compared with noncirrhotic
      patients, patients with cirrhosis had higher Simplified Acute Physiology Score II
      (63.1 +/- 22.7 vs 58.5 +/- 22.8, p < 0.0001) and higher prevalence of renal
      (71.5% vs 54.8%, p < 0.0001) and neurological (26.1% vs 19.5%, p < 0.0001)
      dysfunctions. Over the study period, in-ICU and in-hospital mortality was higher
      in patients with cirrhosis (70.1% and 74.5%) compared with noncirrhotic patients
      (48.3% and 51.7%, p < 0.0001 for both comparisons). Cirrhosis was independently
      associated with an increased risk of death in ICU (adjusted odds ratio = 2.524
      [2.279-2.795]). In patients with cirrhosis, factors independently associated with
      in-ICU mortality were as follows: admission for a medical reason, Simplified
      Acute Physiology Score II, mechanical ventilation, renal replacement therapy,
      spontaneous bacterial peritonitis, positive blood culture, and infection by
      fungus, whereas direct admission and admission during the most recent midterm
      period (2004-2010) were associated with a decreased risk of death. From 1998 to
      2010, prevalence of septic shock in patients with cirrhosis increased from 8.64
      to 15.67 per 1,000 admissions to ICU (p < 0.0001) and their in-ICU mortality
      decreased from 73.8% to 65.5% (p = 0.01) despite increasing Simplified Acute
      Physiology Score II. In-ICU mortality decreased from 84.7% to 68.5% for those
      patients placed under mechanical ventilation (p = 0.004) and from 91.2% to 78.4%
      for those who received renal replacement therapy (p = 0.04). CONCLUSIONS: The
      outcome of patients with cirrhosis and septic shock has markedly improved over
      time, akin to the noncirrhotic population. In 2010, the in-ICU survival rate was
      35%, which now fully justifies to admit these patients to ICU.

PMID- 24732241
TI  - Transcompartmental inflammatory responses in humans: IV versus endobronchial
      administration of endotoxin*.
AB  - OBJECTIVES: Transcompartmental signaling during early inflammation may lead to
      propagation of disease to other organs. The time course and the mechanisms
      involved are still poorly understood. We aimed at comparing acute
      transcompartmental inflammatory responses in humans following lipopolysaccharide
      induced pulmonary and systemic inflammation. DESIGN: Randomized, double-blind,
      placebo-controlled, crossover study. SETTING ICU SUBJECTS: Healthy male
      volunteers. INTERVENTIONS: Fifteen volunteers (mean age, 23; SD, 2 yr) received
      Escherichia coli endotoxin (lipopolysaccharide, 4 ng/kg) IV or endobronchially on
      two different study days. Groups were evaluated by bronchoalveolar lavage at
      baseline (0 hr) and 2, 4, 6, 8, or 24 hours postchallenge. Cardiorespiratory
      variables were continuously recorded throughout the study day, and plasma and
      bronchoalveolar lavage fluid markers of inflammation were measured. MEASUREMENTS
      AND MAIN RESULTS: IV endotoxin elicited a systemic inflammatory response with a
      time-dependent increase and peak in tumor necrosis factor-alpha, interleukin-6,
      and leukocyte counts (all p < 0.001). Furthermore, a delayed (6-8 hr) increase in
      bronchoalveolar lavage fluid interleukin-6 concentration (p < 0.001) and alveolar
      leukocyte count (p = 0.03) and a minor increase in bronchoalveolar lavage fluid
      tumor necrosis factor-alpha were observed (p = 0.06). Endobronchial endotoxin was
      followed by progressive alveolar neutrocytosis and increased bronchoalveolar
      lavage fluid tumor necrosis factor-alpha, interleukin-6, and albumin (all p <
      0.001); a systemic inflammatory response was observed after 2-4 hours, with no
      change in plasma tumor necrosis factor-alpha. CONCLUSIONS: Acute lung or systemic
      inflammation in humans is followed by a transcompartmental proinflammatory
      response, the degree and differential kinetics of which suggests that the
      propagation of inflammation may depend on the primary site of injury.

PMID- 24732242
TI  - Salt reduction in England from 2003 to 2011: its relationship to blood pressure,
      stroke and ischaemic heart disease mortality.
AB  - OBJECTIVES: To determine the relationship between the reduction in salt intake
      that occurred in England, and blood pressure (BP), as well as mortality from
      stroke and ischaemic heart disease (IHD). DESIGN: Analysis of the data from the
      Health Survey for England. SETTING AND PARTICIPANTS: England, 2003 N=9183, 2006
      N=8762, 2008 N=8974 and 2011 N=4753, aged >=16 years. OUTCOMES: BP, stroke and
      IHD mortality. RESULTS: From 2003 to 2011, there was a decrease in mortality from
      stroke by 42% (p<0.001) and IHD by 40% (p<0.001). In parallel, there was a fall
      in BP of 3.0+/-0.33/1.4+/-0.20 mm Hg (p<0.001/p<0.001), a decrease of 0.4+/-0.02
      mmol/L (p<0.001) in cholesterol, a reduction in smoking prevalence from 19% to
      14% (p<0.001), an increase in fruit and vegetable consumption (0.2+/-0.05
      portion/day, p<0.001) and an increase in body mass index (BMI; 0.5+/-0.09
      kg/m(2), p<0.001). Salt intake, as measured by 24 h urinary sodium, decreased by
      1.4 g/day (p<0.01). It is likely that all of these factors (with the exception of
      BMI), along with improvements in the treatments of BP, cholesterol and
      cardiovascular disease, contributed to the falls in stroke and IHD mortality. In
      individuals who were not on antihypertensive medication, there was a fall in BP
      of 2.7+/-0.34/1.1+/-0.23 mm Hg (p<0.001/p<0.001) after adjusting for age, sex,
      ethnic group, education, household income, alcohol consumption, fruit and
      vegetable intake and BMI. Although salt intake was not measured in these
      participants, the fact that the average salt intake in a random sample of the
      population fell by 15% during the same period suggests that the falls in BP would
      be largely attributable to the reduction in salt intake rather than
      antihypertensive medications. CONCLUSIONS: The reduction in salt intake is likely
      to be an important contributor to the falls in BP from 2003 to 2011 in England.
      As a result, it would have contributed substantially to the decreases in stroke
      and IHD mortality.

PMID- 24732243
TI  - The statistics of local motion signals in naturalistic movies.
AB  - Extraction of motion from visual input plays an important role in many visual
      tasks, such as separation of figure from ground and navigation through space.
      Several kinds of local motion signals have been distinguished based on
      mathematical and computational considerations (e.g., motion based on
      spatiotemporal correlation of luminance, and motion based on spatiotemporal
      correlation of flicker), but little is known about the prevalence of these
      different kinds of signals in the real world. To address this question, we first
      note that different kinds of local motion signals (e.g., Fourier, non-Fourier,
      and glider) are characterized by second- and higher-order correlations in slanted
      spatiotemporal regions. The prevalence of local motion signals in natural scenes
      can thus be estimated by measuring the extent to which each of these correlations
      are present in space-time patches and whether they are coherent across
      spatiotemporal scales. We apply this technique to several popular movies. The
      results show that all three kinds of local motion signals are present in natural
      movies. While the balance of the different kinds of motion signals varies from
      segment to segment during the course of each movie, the overall pattern of
      prevalence of the different kinds of motion and their subtypes, and the
      correlations between them, is strikingly similar across movies (but is absent
      from white noise movies). In sum, naturalistic movies contain a diversity of
      local motion signals that occur with a consistent prevalence and pattern of
      covariation, indicating a substantial regularity of their high-order
      spatiotemporal image statistics. 

PMID- 24732245
TI  - Stable cycling of SiO2 nanotubes as high-performance anodes for lithium-ion
      batteries.
AB  - Herein, SiO2 nanotubes have been fabricated via a facile two step hard-template
      growth method and evaluated as an anode for Li-ion batteries. SiO2 nanotubes
      exhibit a highly stable reversible capacity of 1266 mAhg(-1) after 100 cycles
      with negligible capacity fading. SiO2 NT anodes experience a capacity increase
      throughout the first 80 cycles through Si phase growth via SiO2 reduction. The
      hollow morphology of the SiO2 nanotubes accommodates the large volume expansion
      experienced by Si-based anodes during lithiation and promotes preservation of the
      solid electrolyte interphase layer. The thin walls of the SiO2 nanotubes allow
      for effective reduction in Li-ion diffusion path distance and, thus, afford a
      favorable rate cyclability. The high aspect ratio character of these nanotubes
      allow for a relatively scalable fabrication method of nanoscale SiO2-based
      anodes. 

PMID- 24732246
TI  - ATPase/synthase activity of Paracoccus denitrificans Fo.F1 as related to the
      respiratory control phenomenon.
AB  - The time course of ATP synthesis, oxygen consumption, and change in the membrane
      potential in Paracoccus denitrificans inside-out plasma membrane vesicles was
      traced. ATP synthesis initiated by the addition of a limited amount of either ADP
      or inorganic phosphate proceeded up to very low residual concentrations of the
      limiting substrate. Accumulated ATP did not decrease the rate of its synthesis
      initiated by the addition of ADP. The amount of residual ADP determined at State
      4 respiration was independent of ten-fold variation of Pi or the presence of ATP.
      The pH-dependence of Km for Pi could not be fitted to a simple phosphoric acid
      dissociation curve. Partial inhibition of respiration resulted in a decrease in
      the rate of ATP synthesis without affecting the ATP/ADP reached at State 4. At
      pH8.0, hydrolysis of ATP accumulated at State 4 was induced by a low
      concentration of an uncoupler, whereas complete uncoupling results in rapid
      inactivation of ATPase. At pH7.0, no reversal of the ATP synthase reaction by the
      uncoupler was seen. The data show that ATP/ADP*Pi ratio maintained at State 4 is
      not in equilibrium with respiratory-generated driving force. Possible mechanisms
      of kinetic control and unidirectional operation of the Fo.F1-ATP synthase are
      discussed. 

PMID- 24732247
TI  - Campylobacteriosis in New Zealand: room for further improvement.

PMID- 24732248
TI  - Infective endocarditis: trends in the disease and how we study them.

PMID- 24732249
TI  - Estimated community costs of an outbreak of campylobacteriosis resulting from
      contamination of a public water supply in Darfield, New Zealand.
AB  - AIM: To estimate the economic costs to the community of an outbreak of
      campylobacteriosis in August 2012 resulting from contamination of a public water
      supply in Darfield, New Zealand. METHOD: Probable incidence of waterborne disease
      was estimated. Reported cases were scrutinised to identify symptoms, duration,
      hospital admissions and those in the paid workforce. Extra public health and
      local authority costs were calculated. Estimated time off work was multiplied by
      the average wage to obtain a conservative estimate of lost production.
      Sensitivity analysis was used to estimate unreported cases and their associated
      costs. RESULTS: There were 138 cases of confirmed or probable campylobacter, of
      whom 46 sought a medical consultation. Taking into account the usual pyramid of
      non-notified cases, estimates of the population infected range between
      approximately 828 and 1987. The dominant societal cost is lost production from
      time off paid work. Forty-six per cent were in the paid workforce, indicating a
      total estimated economic cost of at least $714,527 but it could have been as high
      as $1.26 million, depending on estimates of unreported cases. CONCLUSION: The
      likely cause of the Darfield outbreak was faecal contamination of the water
      supply, which with a multi-barrier approach would have been entirely preventable.
      The results provide economic evidence to support upgrading of water supplies to
      provide safe water and prevent waterborne disease.

PMID- 24732250
TI  - Determining the health benefits of poultry industry compliance measures: the case
      of campylobacteriosis regulation in New Zealand.
AB  - I undertake a cost benefit analysis of the food safety regulation of production
      of poultry for the New Zealand domestic market and the reduction in foodborne
      illness following this. I take a societal perspective to demonstrate that
      regulation brings both benefits and costs. I derive a cost of illness (COI)
      estimate of foodborne campylobacteriosis from three previous studies. I apply a
      cost benefit analysis (CBA) to this estimate, combined with the cost data
      supplied by industry and the regulator. The benefit:cost ratio was remarkable,
      showing a good return from the combined efforts of industry and the regulator in
      reduction of campylobacteriosis; in dollar terms a gain of at least $57.4 million
      annually. In summary the study demonstrates the high value to the New Zealand
      economy of investment in food safety compliance at the primary industry level. 

PMID- 24732251
TI  - Infective endocarditis in New Zealand: data from the International Collaboration
      on Endocarditis Prospective Cohort Study.
AB  - AIMS: The International Collaboration on Endocarditis Prospective Cohort Study
      (ICE-PCS) collected worldwide data on the presentation, management and outcome of
      infective endocarditis (IE). We present data from patients with endocarditis
      enrolled from New Zealand. METHODS: Patients who fulfilled the Duke criteria for
      definite or probable endocarditis were enrolled from five district health boards:
      Auckland, Counties Manukau, Waitemata, Capital and Coast, and Canterbury, between
      June 2000 and September 2005. RESULTS: There were 336 New Zealand patients
      enrolled in the ICE-PCS. Prosthetic valve endocarditis occurred in 31%.
      Underlying medical conditions were present in 28% of patients, but only 4% of
      patients had rheumatic heart disease. Forty patients (12%) had healthcare
      associated endocarditis. Viridans streptococci were the most common cause of IE
      (32%), followed by Staphylococcus aureus (24%). Patients with S. aureus IE were
      more likely to present within a week of symptom onset than those with viridans
      streptococcus IE (OR 4.18, 95% CI 2.36-7.42). Surgery was performed in 33% of
      patients. In total, 20 patients (6%) died in hospital. Those with endocarditis
      caused by coagulase-negative staphylococci had an increased risk of death
      compared with those viridans streptococcus endocarditis (RR 4.7, 95% CI 1.2-17).
      The risk of stroke was higher in those with endocarditis caused by S. aureus and
      coagulase-negative staphylococci (RR 2.7, 95% CI 1.2-6.05, and 4.9, 95% CI 1.9
      13, respectively). CONCLUSION: While viridans streptococci remain the predominant
      causative organisms of IE in New Zealand, many 'traditional' clinical and
      management aspects of this disease no longer apply. This paper provides a
      reference for local practitioners assessing and managing IE.

PMID- 24732252
TI  - Is refractory angina pectoris a form of chronic pain? A comparison of two patient
      groups receiving spinal cord stimulation therapy.
AB  - AIM: To compare psychological and pain-related characteristics of patients with
      chronic pain and patients with refractory angina pectoris who had been treated
      with spinal cord stimulation (SCS) therapy. METHOD: Twenty-four patients
      receiving SCS therapy were interviewed. Four psychological variables were
      assessed using standardised questionnaires for pain catastrophising, health locus
      of control, anxiety sensitivity, and self-efficacy. Patients also completed the
      revised version of the Short-Form McGill Pain Questionnaire, the Short-Form
      Health Survey, and self-reported measures of global perceived effect, pain,
      functionality, and satisfaction with SCS therapy. RESULTS: Most patients reported
      improvements in pain, functionality, and improvement overall. Some health locus
      of control dimensions were significantly higher for the angina group than the
      chronic pain group, and chronic angina patients reported significantly lower
      levels of intermittent pain. Virtually all patients reported being satisfied with
      SCS therapy. CONCLUSION: Most self-rated psychological and pain-related
      characteristics were no different between the two groups, which gives some
      support to the view that refractory angina is a form of chronic pain. The results
      also add to evidence supporting the use of SCS therapy for refractory angina
      pectoris; however, differences observed on a few variables may indicate points of
      focus for the assessment and treatment of such patients.

PMID- 24732253
TI  - A clinical psychologist in GP-Land: an evaluation of brief psychological
      interventions in primary care.
AB  - AIM: To evaluate the clinical outcomes and other impacts of brief therapy
      provided in a primary care setting by a clinical psychologist who was mainly
      employed in secondary mental health. METHOD: The outcomes of 23 primary care
      patients referred to a clinical psychologist were evaluated using the General
      Health Questionnaire (GHQ), the World Health Organisation Quality of Life
      (WHOQoL) scale, and the Beck Depression Inventory (BDI). A mixture of
      quantitative and qualitative data from patients and staff were analysed to
      identify other impacts of the intervention. RESULTS: Large improvements in BDI,
      GHQ, and WHOQOL scores were found, with strong changes consistent with the
      targets of the intervention. Patients reported primary-based clinical psychology
      input was more convenient and many engaged who had resisted referral to secondary
      mental health services. Other benefits to the service, including improved primary
      secondary service integration, improved primary management of mental health
      difficulties, and improved liaison with mental health specialists, were reported
      by primary health staff. CONCLUSION: Brief psychological interventions by a
      visiting clinical psychologist in a general practice setting had substantial
      benefits for the patients and for the practice. This project indicates the value
      of integrated psychological input consistent with recent moves to better primary
      secondary integration in mental health care.

PMID- 24732254
TI  - A retrospective case series of 44 patients with community-acquired Staphylococcus
      aureus pneumonia.
AB  - AIM: Staphylococcus aureus (S. aureus) community-acquired pneumonia (CAP) is a
      potentially devastating and life-threatening infection. Early detection and
      appropriate treatment is important to prevent morbidity and death. The aim of
      this case series was to investigate the patient demographics, clinical features,
      antibiotic treatment and complications of cases of community-acquired S. aureus
      pneumonia occurring in the Wellington region. METHOD: The case records of
      patients with radiographically confirmed community-acquired pneumonia and
      laboratory evidence to support S. aureus as the causative organism admitted to
      Wellington Regional Hospital over a 5-year period (2007-2012) were
      retrospectively reviewed. RESULTS: A total of 48 presentations in 44 patients met
      the inclusion criteria. The majority of patients (63.6%) had underlying
      comorbidities. Although the mean CURB65 score was only one and fever was
      uncommon, 30% of patients were admitted to ICU and 16% died in hospital.
      Significant infective complications occurred in 48% with new lung cavitation in
      20%. CONCLUSION: This series of patients with staphylococcal pneumonia confirms
      the significant morbidity and mortality of the infection. A low CURB65 score and
      lack of objective fever should not detract from the possibility of S. aureus. The
      presence of bacteraemia in patients with S. aureus pneumonia needs to be regarded
      as a potentially deleterious finding that may necessitate a change in treatment.

PMID- 24732255
TI  - Medical image. Asystole with carotid sinus hypersensitivity.

PMID- 24732256
TI  - Medical image. A rare case of occult gastrointestinal bleeding: a submucosal
      colonic lipoma mimicking a malignant tumour.

PMID- 24732257
TI  - Is Campylobacter consisus an unrecognised cause of diarrhoea in New Zealand?

PMID- 24732258
TI  - Prevalence of malaria parasitemia and purchase of artemisinin-based combination
      therapies (ACTs) among drug shop clients in two regions in Tanzania with ACT
      subsidies.
AB  - BACKGROUND: Throughout Africa, many people seek care for malaria in private
      sector drug shops where diagnostic testing is often unavailable. Recently,
      subsidized artemisinin-based combination therapies (ACTs), a first-line
      medication for uncomplicated malaria, were made available in these drug shops in
      Tanzania. This study assessed the prevalence of malaria among and purchase of
      ACTs by drug shop clients in the setting of a national ACT subsidy program and
      sub-national drug shop accreditation program. METHOD AND FINDINGS: A cross
      sectional survey of drug shop clients was performed in two regions in Tanzania,
      one with a government drug shop accreditation program and one without, from March
      May, 2012. Drug shops were randomly sampled from non-urban districts. Shop
      attendants were interviewed about their education, training, and accreditation
      status. Clients were interviewed about their symptoms and medication purchases,
      then underwent a limited physical examination and laboratory testing for malaria.
      Malaria prevalence and predictors of ACT purchase were assessed using univariate
      analysis and multiple logistic regression. Amongst 777 clients from 73 drug
      shops, the prevalence of laboratory-confirmed malaria was 12% (95% CI: 6-18%).
      Less than a third of clients with malaria had purchased ACTs, and less than a
      quarter of clients who purchased ACTs tested positive for malaria. Clients were
      more likely to have purchased ACTs if the participant was <5 years old (aOR: 6.6;
      95% CI: 3.9-11.0) or the shop attendant had >5 years, experience (aOR: 2.8; 95%
      CI: 1.2-6.3). Having malaria was only a predictor of ACT purchase in the region
      with a drug shop accreditation program (aOR: 3.4; 95% CI: 1.5-7.4). CONCLUSION:
      Malaria is common amongst persons presenting to drug shops with a complaint of
      fever. The low proportion of persons with malaria purchasing ACTs, and the high
      proportion of ACTs going to persons without malaria demonstrates a need to better
      target who receives ACTs in these drug shops.

PMID- 24732260
TI  - Nanostructured drug delivery for better management of tuberculosis.
AB  - With almost 30% of the world population suffering from tuberculosis (TB)
      including its resurgence in the developed world, better management of this global
      threat is highly desired. The emergence of multidrug-resistant TB (MDR-TB)
      against first-line drugs and extensively drug resistant TB (XDR-TB) due to misuse
      of second-line antitubercular drugs (ATDs) is a further concern. Recommended
      treatment involves long term and multiple drug therapy with severe side effects.
      In this context, nanostructured systems efficiently encapsulating considerable
      amounts of ATDs, eliciting controlled, sustained and more profound effect to
      overcome the need to administer ATDs at high and frequent doses, would assist in
      improving patient compliance and circumvent hepatotoxicity and/or
      nephrotoxicity/ocular toxicity/ototoxicity associated with the prevalent first
      line chemotherapy. Nanostructured delivery systems constitute a wide range of
      systems varying from liposomes, micelles, micro- and nanoemulsions, to polymeric
      nanoparticles (PNPs) and solid lipid nanoparticles (SLNs). Improved
      bioavailability, solubility, stability and biocompatibility make them an ideal
      choice for delivery of ATDs. Present review comprehensively covers research
      carried out on first-line antitubercular drug therapy using these nanostructured
      systems. 

PMID- 24732261
TI  - Inpatient and emergent resource use of patients on dialysis at an academic
      medical center.
AB  - BACKGROUND/AIM: End-stage renal disease patients require resources for emergent
      and inpatient care in addition to ambulatory dialysis. There are two dialysis
      modalities and settings which patients switch between. Our aim was to
      characterize the patterns and reasons for switching, as well as the emergent and
      inpatient utilization of these patients at the University Health Network.
      METHODS: Patients who received chronic dialysis between March 1, 2006, and April
      30, 2011, were identified. Utilization was measured by emergency department (ED)
      visits, inpatient hospitalizations, and bed-days occupied per year. RESULTS: Out
      of 576 patients identified, 18.6% switched modality and/or setting. The majority
      of switches occurred during the first year of dialysis. Patients who switched had
      increased utilization compared to those on a continuous modality/setting.
      Overall, patients had a median rate of 0.91 ED visits per patient-year, compared
      to 1.56 for patients who switched modality and setting. Median inpatient bed
      resource requirement was 4.46 bed-days/patient-year overall, compared to 8.91 for
      patients who switched modality and setting. CONCLUSIONS: Emergent and inpatient
      utilization is related to the setting and modality of dialysis, although
      differences are partly explained by comorbidities. Patients who switch modalities
      use more resources and may be a prime population for interventions.

PMID- 24732262
TI  - Chou's pseudo amino acid composition improves sequence-based antifreeze protein
      prediction.
AB  - Antifreeze proteins (AFP) in living organisms play a key role in their tolerance
      to extremely cold temperatures and have a wide range of biotechnological
      applications. But on account of diversity, their identification has been
      challenging to biologists. Earlier work explored in this area has yet to cover
      introduction of sequence order information which is known to represent important
      properties of various proteins and protein systems for prediction purposes. In
      this study, the effect of Chou's pseudo amino acid composition that presents
      sequence order of proteins was systematically explored using support vector
      machines for AFP prediction. Our findings suggest that introduction of sequence
      order information helps identify AFPs with an accuracy of 84.75% on independent
      test dataset, outperforming approaches such as AFP-Pred and iAFP. The relative
      performance calculated using Youden's Index (Sensitivity+Specificity-1) was found
      to be 0.71 for our predictor (AFP-PseAAC), 0.48 for AFP-Pred and 0.05 for iAFP.
      We hope this novel prediction approach will aid in AFP based research for
      biotechnological applications.

PMID- 24732259
TI  - Matrix and backstage: cellular substrates for viral vaccines.
AB  - Vaccines are complex products that are manufactured in highly dynamic processes.
      Cellular substrates are one critical component that can have an enormous impact
      on reactogenicity of the final preparation, level of attenuation of a live virus,
      yield of infectious units or antigens, and cost per vaccine dose. Such parameters
      contribute to feasibility and affordability of vaccine programs both in
      industrialized countries and developing regions. This review summarizes the
      diversity of cellular substrates for propagation of viral vaccines from primary
      tissue explants and embryonated chicken eggs to designed continuous cell lines of
      human and avian origin. 

PMID- 24732264
TI  - Abstracts of the 2014 Annual Meeting of the Society for Investigative
      Dermatology, May 7 - 10, 2014, Albuquerque, New Mexico.

PMID- 24732263
TI  - Layered decomposition for the model order reduction of timescale separated
      biochemical reaction networks.
AB  - Biochemical reaction networks tend to exhibit behaviour on more than one
      timescale and they are inevitably modelled by stiff systems of ordinary
      differential equations. Singular perturbation is a well-established method for
      approximating stiff systems at a given timescale. Standard applications of
      singular perturbation partition the state variable into fast and slow modules and
      assume a quasi-steady state behaviour in the fast module. In biochemical reaction
      networks, many reactants may take part in both fast and slow reactions; it is not
      necessarily the case that the reactants themselves are fast or slow.
      Transformations of the state space are often required in order to create fast and
      slow modules, which thus no longer model the original species concentrations.
      This paper introduces a layered decomposition, which is a natural choice when
      reaction speeds are separated in scale. The new framework ensures that model
      reduction can be carried out without seeking state space transformations, and
      that the effect of the fast dynamics on the slow timescale can be described
      directly in terms of the original species. 

PMID- 24732279
TI  - Separating the effects of water physicochemistry and sediment contamination on
      Chironomus tepperi (Skuse) survival, growth and development: a boosted regression
      tree approach.
AB  - More comprehensive ecological risk assessment procedures are needed as the
      unprecedented rate of anthropogenic disturbances to aquatic ecosystems continues.
      Identifying the effects of pollutants on aquatic ecosystems is difficult,
      requiring the individual and joint effects of a range of natural and
      anthropogenic factors to be isolated, often via the analysis of large,
      complicated datasets. Ecotoxicologists have traditionally used multiple
      regression to analyse such datasets, but there are inherent problems with this
      approach and a need to consider other potentially more suitable methods. Sediment
      pollution can cause a range of negative effects on aquatic animals, and these are
      used as the basis for toxicity bioassays to measure the biological impact of
      pollution and the success of remediation efforts. However, experimental artefacts
      can also lead to sediments being incorrectly classed as toxic in such studies.
      Understanding the influence of potentially confounding factors will help more
      accurate assessments of sediment pollution. In this study, we analysed
      standardised sediment bioassays conducted using the chironomid Chironomus
      tepperi, with the aim of modelling the impact of sediment toxicants and water
      physico-chemistry on four endpoints (survival, growth, median emergence day, and
      number of emerging adults). We used boosted regression trees (BRT), a method that
      has a number of advantages over multiple regression, to model bioassay endpoints
      as a function of water chemistry, sediment quality and underlying geology.
      Endpoints were generally influenced most strongly by water quality parameters and
      nutrients, although some metals negatively influenced emergence endpoints. Sub
      lethal endpoints were generally better predicted than lethal endpoints; median
      emergence day was the most sensitive endpoint examined in this study, while the
      number of emerging adults was the least sensitive. We tested our modelling
      results by experimentally manipulating sediment and observing the impact on C.
      tepperi endpoints. For survival, experimental observations were accurately
      predicted by models, which highlighted the importance of conductivity and
      dissolved oxygen for this endpoint. In comparison, experimental median emergence
      day was poorly modelled, most likely due to the influence of a wider range of
      predictors identified as being important influences on this endpoint in models.
      To demonstrate how BRT model results compare to more traditional techniques, we
      analysed survival data using multiple regression. Both models yielded similar
      results, but boosted regression trees offer important advantages over multiple
      regression. Our results illustrate how boosted regression trees can be used to
      analyse complex ecotoxicological datasets, and reinforces the importance of water
      chemistry in sediment toxicology. 

PMID- 24732280
TI  - Comparative genomic analysis and virulence differences in closely related
      salmonella enterica serotype heidelberg isolates from humans, retail meats, and
      animals.
AB  - Salmonella enterica subsp. enterica serovar Heidelberg (S. Heidelberg) is one of
      the top serovars causing human salmonellosis. Recently, an antibiotic-resistant
      strain of this serovar was implicated in a large 2011 multistate outbreak
      resulting from consumption of contaminated ground turkey that involved 136
      confirmed cases, with one death. In this study, we assessed the evolutionary
      diversity of 44 S. Heidelberg isolates using whole-genome sequencing (WGS)
      generated by the 454 GS FLX (Roche) platform. The isolates, including 30 with
      nearly indistinguishable (one band difference) Xbal pulsed-field gel
      electrophoresis patterns (JF6X01.0032, JF6X01.0058), were collected from various
      sources between 1982 and 2011 and included nine isolates associated with the 2011
      outbreak. Additionally, we determined the complete sequence for the chromosome
      and three plasmids from a clinical isolate associated with the 2011 outbreak
      using the Pacific Biosciences (PacBio) system. Using single-nucleotide
      polymorphism (SNP) analyses, we were able to distinguish highly clonal isolates,
      including strains isolated at different times in the same year. The isolates from
      the recent 2011 outbreak clustered together with a mean SNP variation of only 17
      SNPs. The S. Heidelberg isolates carried a variety of phages, such as prophage
      P22, P4, lambda-like prophage Gifsy-2, and the P2-like phage which carries the
      sopE1 gene, virulence genes including 62 pathogenicity, and 13 fimbrial markers
      and resistance plasmids of the incompatibility (Inc)I1, IncA/C, and IncHI2
      groups. Twenty-one strains contained an IncX plasmid carrying a type IV secretion
      system. On the basis of the recent and historical isolates used in this study,
      our results demonstrated that, in addition to providing detailed genetic
      information for the isolates, WGS can identify SNP targets that can be utilized
      for differentiating highly clonal S. Heidelberg isolates. 

PMID- 24732281
TI  - Systematic variation in the pattern of gene paralog retention between the teleost
      superorders Ostariophysi and Acanthopterygii.
AB  - Teleost fish underwent whole-genome duplication around 450 Ma followed by
      diploidization and loss of 80-85% of the duplicated genes. To identify a deep
      signature of this teleost-specific whole-genome duplication (TSGD), we searched
      for duplicated genes that were systematically and uniquely retained in one or
      other of the superorders Ostariophysi and Acanthopterygii. TSGD paralogs
      comprised 17-21% of total gene content. Some 2.6% (510) of TSGD paralogs were
      present as pairs in the Ostariophysi genomes of Danio rerio (Cypriniformes) and
      Astyanax mexicanus (Characiformes) but not in species from four orders of
      Acanthopterygii (Gasterosteiformes, Gasterosteus aculeatus; Tetraodontiformes,
      Tetraodon nigroviridis; Perciformes, Oreochromis niloticus; and Beloniformes,
      Oryzias latipes) where a single copy was identified. Similarly, 1.3% (418) of
      total gene number represented cases where TSGD paralogs pairs were systematically
      retained in the Acanthopterygian but conserved as a single copy in Ostariophysi
      genomes. We confirmed the generality of these results by phylogenetic and synteny
      analysis of 40 randomly selected linage-specific paralogs (LSPs) from each
      superorder and completed with the transcriptomes of three additional Ostariophysi
      species (Ictalurus punctatus [Siluriformes], Sinocyclocheilus species
      [Cypriniformes], and Piaractus mesopotamicus [Characiformes]). No chromosome bias
      was detected in TSGD paralog retention. Gene ontology (GO) analysis revealed
      significant enrichment of GO terms relative to the human GO SLIM database for
      "growth," "Cell differentiation," and "Embryo development" in Ostariophysi and
      for "Transport," "Signal Transduction," and "Vesicle mediated transport" in
      Acanthopterygii. The observed patterns of paralog retention are consistent with
      different diploidization outcomes having contributed to the
      evolution/diversification of each superorder.

PMID- 24732283
TI  - Serum triglyceride levels correlated with the rate of change in insulin secretion
      over two years in prediabetic subjects.
AB  - BACKGROUND/AIMS: Increased triglyceride (TG) and decreased high-density
      lipoprotein cholesterol (HDL-C) levels are considered risk factors for diabetes
      among prediabetic subjects. In this study, we retrospectively investigated the
      relationship between lipid profiles and the rate of change in early-phase insulin
      secretion in prediabetic subjects. METHODS: To evaluate insulin secretion, 50
      prediabetic subjects underwent a 75-gram oral glucose tolerance test at the
      beginning of the study (baseline), and they were reexamined after a 2-year
      interval. The results were expressed as insulinogenic index (IGI) and disposition
      index (DI). RESULTS: The lipid profiles and indices of insulin secretion had not
      significantly changed over 2 years. However, Pearson's correlation analyses
      indicated that the rate of change in IGI and DI was negatively correlated with
      log-transformed baseline TG level, but not with baseline HDL-C level. Multiple
      linear regression analysis confirmed that the rate of change in IGI and DI was
      negatively correlated with the log-transformed baseline TG level (beta = -0.38, p
      = 0.006, and beta = -0.39, p = 0.006, respectively). CONCLUSIONS: Baseline TG
      level of prediabetic subjects appeared to be associated with rate of change in
      IGI and DI over a 2-year period, indicating that TG levels among prediabetic
      subjects should be carefully monitored.

PMID- 24732282
TI  - Comparative genomics of flatworms (platyhelminthes) reveals shared genomic
      features of ecto- and endoparastic neodermata.
AB  - The ectoparasitic Monogenea comprise a major part of the obligate parasitic
      flatworm diversity. Although genomic adaptations to parasitism have been studied
      in the endoparasitic tapeworms (Cestoda) and flukes (Trematoda), no
      representative of the Monogenea has been investigated yet. We present the high
      quality draft genome of Gyrodactylus salaris, an economically important
      monogenean ectoparasite of wild Atlantic salmon (Salmo salar). A total of 15,488
      gene models were identified, of which 7,102 were functionally annotated. The
      controversial phylogenetic relationships within the obligate parasitic Neodermata
      were resolved in a phylogenomic analysis using 1,719 gene models (alignment
      length of >500,000 amino acids) for a set of 16 metazoan taxa. The Monogenea were
      found basal to the Cestoda and Trematoda, which implies ectoparasitism being
      plesiomorphic within the Neodermata and strongly supports a common origin of
      complex life cycles. Comparative analysis of seven parasitic flatworm genomes
      identified shared genomic features for the ecto- and endoparasitic lineages, such
      as a substantial reduction of the core bilaterian gene complement, including the
      homeodomain-containing genes, and a loss of the piwi and vasa genes, which are
      considered essential for animal development. Furthermore, the shared loss of
      functional fatty acid biosynthesis pathways and the absence of peroxisomes, the
      latter organelles presumed ubiquitous in eukaryotes except for parasitic
      protozoans, were inferred. The draft genome of G. salaris opens for future in
      depth analyses of pathogenicity and host specificity of poorly characterized G.
      salaris strains, and will enhance studies addressing the genomics of host
      parasite interactions and speciation in the highly diverse monogenean flatworms. 

PMID- 24732284
TI  - Predicting persistence of functional abdominal pain from childhood into young
      adulthood.
AB  - BACKGROUND & AIMS: Pediatric functional abdominal pain has been linked to
      functional gastrointestinal disorders (FGIDs) in adulthood, but little is known
      about patient characteristics in childhood that increase the risk for FGID in
      young adulthood. We investigated the contribution of gastrointestinal symptoms,
      extraintestinal somatic symptoms, and depressive symptoms in pediatric patients
      with functional abdominal pain and whether these predicted FGIDs later in life.
      METHODS: In a longitudinal study, consecutive new pediatric patients, diagnosed
      with functional abdominal pain in a subspecialty clinic, completed a
      comprehensive baseline evaluation of the severity of their physical and emotional
      symptoms. They were contacted 5 to 15 years later and evaluated, based on Rome
      III symptom criteria, for abdominal pain-related FGIDs, including irritable bowel
      syndrome, functional dyspepsia, functional abdominal pain syndrome, and abdominal
      migraine. Controlling for age, sex, baseline severity of abdominal pain, and time
      to follow-up evaluation, multivariable logistic regression was used to evaluate
      the association of baseline gastrointestinal, extraintestinal somatic, and
      depressive symptoms in childhood with FGID in adolescence and young adulthood.
      RESULTS: Of 392 patients interviewed an average of 9.2 years after their initial
      evaluation, 41% (n = 162) met symptom criteria for FGID; most met the criteria
      for irritable bowel syndrome. Extraintestinal somatic and depressive symptoms at
      the initial pediatric evaluation were significant predictors of FGID later in
      life, after controlling for initial levels of GI symptoms. Age, sex, and
      abdominal pain severity at initial presentation were not significant predictors
      of FGID later in life. CONCLUSIONS: In pediatric patients with functional
      abdominal pain, assessment of extraintestinal and depressive symptoms may be
      useful in identifying those at risk for FGID in adolescence and young adulthood.

PMID- 24732285
TI  - Complete endoscopic mucosal resection is effective and durable treatment for
      Barrett's-associated neoplasia.
AB  - BACKGROUND & AIMS: Barrett's esophagus (BE) with high-grade dysplasia (HGD) or
      intramucosal carcinoma (IMC) is treated by complete eradication of areas of BE by
      endoscopic mucosal resection (EMR). By using this approach, histologic analysis
      also can be performed. We investigated the effectiveness, safety, and durability
      of this approach, as well as its use in diagnosis after a single referral.
      METHODS: We collected data from 107 patients who were referred to the Center for
      Endoscopic Research and Therapeutics at the University of Chicago for BE (mean
      length, 3.6 cm) with suspected HGD or IMC, from August 2003 through December
      2012. All patients underwent EMR and were followed up through January 2014 (mean
      follow-up time, 40.6 mo). The primary outcome was treatment efficacy (complete
      eradication of BE and associated neoplasia); secondary outcomes included safety,
      durability, and accuracy of diagnosis. RESULTS: BE was eradicated completely by
      EMR in 80.4% (86 of 107) of patients based on intention-to-treat analysis, and in
      98.8% (79 of 80) of patients based on per-protocol analysis. The diagnosis was
      changed for 25% of patients after EMR, including 4 cases that initially were
      diagnosed as HGD by biopsy analysis and subsequently were found to have evidence
      of submucosal invasion when EMR specimens were assessed. Strictures and
      symptomatic dysphagia developed in 41.1% and 37.3% of patients, respectively,
      with an average of 2.3 dilations required. Perforations occurred in 2 patients
      after EMR and in 1 patient after dilation. HGD and IMC recurred in 1 patient
      each; both were treated successfully with EMR. Based on pathology analysis of the
      most recently collected specimens, 71.6% of patients (53 of 74) were in complete
      remission from intestinal metaplasia and 100% were in complete remission from HGD
      (74 of 74) or cancer (74 of 74). CONCLUSIONS: For patients with BE with HGD or
      neoplasia, complete EMR is an effective and durable treatment and is a relatively
      safe technique. Specimens collected by EMR also can be analyzed histologically to
      aid in diagnosis. The common complication of EMR is esophageal stricture, which
      can be addressed with endoscopic dilation.

PMID- 24732286
TI  - Application of falling-needle rheometry to highly concentrated DNA solutions.
AB  - High-concentration DNA solutions are common both in vitro and in vivo, and
      understanding the rheological properties is a critical area of bioscience. Our
      previous measurements on high-concentration DNA solutions (2-6 mg/ml)
      interestingly provided evidence for a viscosity maximum with temperature. Under
      the influence of temperature, the measured viscosities indicated distinct
      differences in the interactions of highly polymerized DNA in unbuffered and
      buffered aqueous solutions. Under the same conditions, the buffered solutions
      were always less viscous, and in addition the viscosity maximum was not observed.
      In this research we have utilized a falling-needle rheometer in order to gain
      more insight into the nature of the previously observed viscosity maxima. The
      shape of the flow curves for all the DNA solutions indicated that the solutions
      are shear-thinning and has allowed us to confirm the existence of the viscosity
      maximum in unbuffered DNA solutions. Also we have been able to measure flow
      curves at very low shear rates, <10 s-1. These results showed that the flow
      curves intersect and that the lower the concentration of DNA in solution, the
      lower is the temperature where the flow curves will intersect. Thus, the
      viscosity-temperature dependence is also a function of the shear rates
      experienced by the solution. Finally, as expected, the flow behavior of the DNA
      solutions becomes more Newtonian with increasing temperature, and there appears
      to be a small yield stress that decreases with increasing temperature.

PMID- 24732287
TI  - Evaluation of the new consensus criteria for the diagnosis of primary progressive
      aphasia using fluorodeoxyglucose positron emission tomography.
AB  - BACKGROUND: New consensus criteria have been proposed to classify primary
      progressive aphasia (PPA) into three variants: agrammatic, semantic, and
      logopenic. Some studies have subsequently addressed the usefulness of these
      criteria, with controversial results. We aimed to determine the correlation
      between the clinical diagnosis according to the new criteria and brain topography
      in (18)F-fluorodeoxyglucose positron emission tomography (FDG-PET). METHODS:
      Patients meeting the PPA criteria were prospectively recruited in a single center
      during a period of 18 months. They were clinically classified according to the
      new criteria and underwent FDG-PET. The cerebral metabolism of each patient was
      compared to a healthy control group using statistical parametric mapping. The
      expected variant according to the analysis of PET imaging was compared with the
      clinical diagnosis using the consensus criteria. RESULTS: 32 patients were
      included. 90% of them fulfilled the consensus criteria and could be classified
      into one of the three clinical variants. The correlation with the cerebral
      metabolism was high: the kappa index was 0.91 in the agrammatic variant, 0.71 in
      the semantic variant, and 0.74 in the logopenic variant. CONCLUSIONS: A high
      correlation with the diagnosis obtained using FDG-PET was found. However, an
      overdiagnosis of the logopenic variant was observed. These results support the
      use of the new criteria, but some modifications or complementary studies may
      still be necessary.

PMID- 24732288
TI  - Development and comparative evaluation of SYBR Green I-based one-step real-time
      RT-PCR assay for detection and quantification of West Nile virus in human
      patients.
AB  - The recent outbreaks of West Nile Virus (WNV) in the Northeastern American
      continents and other regions of the world have made it essential to develop an
      efficient protocol for surveillance of WN virus. Nucleic acid based techniques
      like, RT-PCR have the advantage of sensitivity, specificity and rapidity. A one
      step single tube Env gene specific real-time RT-PCR was developed for early and
      reliable clinical diagnosis of WNV infection in clinical samples. The
      applicability of this assay for clinical diagnosis was validated with 105
      suspected acute-phase serum and plasma samples from the recent epidemic of
      mysterious fever in Tamil Nadu, India in 2009-10. The comparative evaluation
      revealed the higher sensitivity of real-time RT-PCR assay by picking up 4
      additional samples with low copy number of template in comparison to conventional
      RT-PCR. All the real-time positive samples further confirmed by CDC reported
      TaqMan real-time RT-PCR and quantitative real-time RT-PCR assays for the
      simultaneous detection of WNV lineage 1 and 2 strains. The quantitation of the
      viral load samples was done using a standard curve. These findings demonstrated
      that the assay has the potential usefulness for clinical diagnosis due to
      detection and quantification of WNV in acute-phase patient serum samples. 

PMID- 24732289
TI  - Mycobactericidal activity of sutezolid (PNU-100480) in sputum (EBA) and blood
      (WBA) of patients with pulmonary tuberculosis.
AB  - RATIONALE: Sutezolid (PNU-100480) is a linezolid analog with superior
      bactericidal activity against Mycobacterium tuberculosis in the hollow fiber,
      whole blood and mouse models. Like linezolid, it is unaffected by mutations
      conferring resistance to standard TB drugs. This study of sutezolid is its first
      in tuberculosis patients. METHODS: Sputum smear positive tuberculosis patients
      were randomly assigned to sutezolid 600 mg BID (N = 25) or 1200 mg QD (N = 25),
      or standard 4-drug therapy (N = 9) for the first 14 days of treatment. Effects on
      mycobacterial burden in sputum (early bactericidal activity or EBA) were
      monitored as colony counts on agar and time to positivity in automated liquid
      culture. Bactericidal activity was also measured in ex vivo whole blood cultures
      (whole blood bactericidal activity or WBA) inoculated with M. tuberculosis H37Rv.
      RESULTS: All patients completed assigned treatments and began subsequent standard
      TB treatment according to protocol. The 90% confidence intervals (CI) for
      bactericidal activity in sputum over the 14 day interval excluded zero for all
      treatments and both monitoring methods, as did those for cumulative WBA. There
      were no treatment-related serious adverse events, premature discontinuations, or
      dose reductions due to laboratory abnormalities. There was no effect on the QT
      interval. Seven sutezolid-treated patients (14%) had transient, asymptomatic ALT
      elevations to 173+/-34 U/L on day 14 that subsequently normalized promptly; none
      met Hy's criteria for serious liver injury. CONCLUSIONS: The mycobactericidal
      activity of sutezolid 600 mg BID or 1200 mg QD was readily detected in sputum and
      blood. Both schedules were generally safe and well tolerated. Further studies of
      sutezolid in tuberculosis treatment are warranted. TRIAL REGISTRATION:
      ClinicalTrials.gov NCT01225640.

PMID- 24732290
TI  - Acetaminophen attenuates lipid peroxidation in children undergoing
      cardiopulmonary bypass.
AB  - OBJECTIVE: Hemolysis, occurring during cardiopulmonary bypass, is associated with
      lipid peroxidation and postoperative acute kidney injury. Acetaminophen inhibits
      lipid peroxidation catalyzed by hemeproteins and in an animal model attenuated
      rhabdomyolysis-induced acute kidney injury. This pilot study tests the hypothesis
      that acetaminophen attenuates lipid peroxidation in children undergoing
      cardiopulmonary bypass. DESIGN: Single-center prospective randomized double
      blinded study. SETTING: University-affiliated pediatric hospital. PATIENTS:
      Thirty children undergoing elective surgical correction of a congenital heart
      defect. INTERVENTIONS: Patients were randomized to acetaminophen (OFIRMEV
      [acetaminophen] injection; Cadence Pharmaceuticals, San Diego, CA) or placebo
      every 6 hours for four doses starting before the onset of cardiopulmonary bypass.
      MEASUREMENT AND MAIN RESULTS: Markers of hemolysis, lipid peroxidation (isofurans
      and F2-isoprostanes), and acute kidney injury were measured throughout the
      perioperative period. Cardiopulmonary bypass was associated with a significant
      increase in free hemoglobin (from a prebypass level of 9.8 +/- 6.2 mg/dL to a
      peak of 201.5 +/- 42.6 mg/dL postbypass). Plasma and urine isofuran and F2
      isoprostane concentrations increased significantly during surgery. The magnitude
      of increase in plasma isofurans was greater than the magnitude in increase in
      plasma F2-isoprostanes. Acetaminophen attenuated the increase in plasma isofurans
      compared with placebo (p = 0.02 for effect of study drug). There was no
      significant effect of acetaminophen on plasma F2-isoprostanes or urinary makers
      of lipid peroxidation. Acetaminophen did not affect postoperative creatinine,
      urinary neutrophil gelatinase-associated lipocalin, or prevalence of acute kidney
      injury. CONCLUSION: Cardiopulmonary bypass in children is associated with
      hemolysis and lipid peroxidation. Acetaminophen attenuated the increase in plasma
      isofuran concentrations. Future studies are needed to establish whether other
      therapies that attenuate or prevent the effects of free hemoglobin result in more
      effective inhibition of lipid peroxidation in patients undergoing cardiopulmonary
      bypass.

PMID- 24732291
TI  - Optimizing care of adults with congenital heart disease in a pediatric
      cardiovascular ICU using electronic clinical decision support*.
AB  - OBJECTIVES: The optimal location for postoperative cardiac care of adults with
      congenital heart disease is controversial. Some congenital heart surgeons operate
      on these adults in children's hospitals with postoperative care provided by
      pediatric critical care teams who may be unfamiliar with adult national
      performance measures. This study tested the hypothesis that Clinical Decision
      Support tools integrated into the clinical workflow would facilitate improved
      compliance with The Joint Commission Surgical Care Improvement Project
      performance measures in adults recovering from cardiac surgery in a children's
      hospital. DESIGN: Retrospective chart review comparing compliance pre- and post
      Clinical Decision Support intervention for Surgical Care Improvement Project
      measures addressed in the critical care unit: appropriate cessation of
      prophylactic antibiotics; controlled blood glucose; urinary catheter removal; and
      reinitiation of preoperative beta-blocker when indicated. SETTING: Cardiovascular
      ICU in a quaternary care freestanding children's hospital. PATIENTS: The cohort
      included 114 adults 18-70 years old recovering from cardiac surgery in our
      pediatric cardiovascular ICU. INTERVENTIONS: Clinical Decision Support tools
      including data-triggered alerts, smart documentation forms, and order sets with
      conditional logic were integrated into the workflow. MEASUREMENTS AND MAIN
      RESULTS: Compliance with antibiotic discontinuation was 100% pre- and
      postintervention. Compliance rates improved for glucose control (p = 0.007) and
      urinary catheter removal (p = 0.05). Documentation of beta-blocker therapy
      (nonexistent preintervention) was 100% postintervention. Composite compliance for
      all measures increased from 53% to 84% (p = 0.002). There were no complications
      related to institution of the Surgical Care Improvement Project measures. There
      was no in-hospital mortality. CONCLUSIONS: Compliance with the national adult
      postoperative performance measures can be excellent in a children's hospital with
      the help of Clinical Decision Support tools. This represents an important step
      toward providing high-quality care to a growing population of adults with
      congenital heart disease who may receive care in a pediatric center.

PMID- 24732292
TI  - Survey on stated transfusion practices in PICUs*.
AB  - OBJECTIVES: To analyze the RBC transfusion practice patterns among pediatric
      intensivists in light of the new evidence advocating for a restrictive
      transfusion strategy. DESIGN: Self-administered questionnaire. SETTING: PICUs.
      SUBJECTS: Intensivists and fellows in pediatric critical care medicine.
      INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Scenario-based survey carried
      out among North American and European intensivists, working in tertiary-care
      PICUs. Respondents were asked to report their decisions with regard to RBC
      transfusion in stable critically ill children with bronchiolitis, septic shock,
      trauma, or tetralogy of Fallot repair scenarios. Answers were compared with those
      of a similar scenario-based survey administered to pediatric intensivists in
      1997. Ninety-seven respondents were retained for the study, the majority from the
      United States, Canada, and France. In 2010, respondents reported that the mean
      (+/- SD) transfusion threshold was a hemoglobin level of 7.7 +/- 1.0 g/dL for
      bronchiolitis, 8.1 +/- 1.2 g/dL for trauma, 9.1 +/- 1.2 g/dL for a tetralogy of
      Fallot repair, and 9.2 +/- 1.0 g/dL for septic shock. For all clinical scenarios,
      there was a trend toward a more restrictive transfusion approach (a threshold <=
      7 g/dL) in 2010 compared with 1997: a restrictive strategy was adopted by 55.7%
      of respondents in 2010 versus 37.0% in 1997 (p = 0.01) with the scenario of
      bronchiolitis, 8.3% versus 3.4% (p = 0.16) with septic shock, 38.1% versus 9.0%
      (p < 0.001) with trauma, and 16.0% versus 7.9% (p = 0.10) with tetralogy of
      Fallot repair. CONCLUSIONS: Stated transfusion practice patterns of pediatric
      intensivists appear to be evolving toward a more restrictive approach two and a
      half years after the publication of the Transfusion Requirement in PICU trial.
      Incomplete implementation of new knowledge with regard to the safety of a
      restrictive transfusion approach in stable PICU patients is perplexing and
      requires further studies.

PMID- 24732293
TI  - Validation of DNA methylation profiling in formalin-fixed paraffin-embedded
      samples using the Infinium HumanMethylation450 Microarray.
AB  - A formalin-fixed paraffin-embedded (FFPE) sample usually yields highly degraded
      DNA, which limits the use of techniques requiring high-quality DNA, such as
      Infinium Methylation microarrays. To overcome this restriction, we have applied
      an FFPE restoration procedure consisting of DNA repair and ligation processes in
      a set of paired fresh-frozen (FF) and FFPE samples. We validated the FFPE results
      in comparison with matched FF samples, enabling us to use FFPE samples on the
      Infinium HumanMethylation450 Methylation array. 

PMID- 24732294
TI  - Ultrasmall SnO2 nanocrystals: hot-bubbling synthesis, encapsulation in carbon
      layers and applications in high capacity Li-ion storage.
AB  - Ultrasmall SnO2 nanocrystals as anode materials for lithium-ion batteries (LIBs)
      have been synthesized by bubbling an oxidizing gas into hot surfactant solutions
      containing Sn-oleate complexes. Annealing of the particles in N2 carbonifies the
      densely packed surface capping ligands resulting in carbon encapsulated SnO2
      nanoparticles (SnO2/C). Carbon encapsulation can effectively buffer the volume
      changes during the lithiation/delithiation process. The assembled SnO2/C thus
      deliver extraordinarily high reversible capacity of 908 mA.h.g(-1) at 0.5 C as
      well as excellent cycling performance in the LIBs. This method demonstrates the
      great potential of SnO2/C nanoparticles for the design of high power LIBs. 

PMID- 24732295
TI  - Ultrasonographic assessment of the diaphragm in chronic obstructive pulmonary
      disease patients: relationships with pulmonary function and the influence of body
      composition - a pilot study.
AB  - BACKGROUND: Skeletal muscle weakness with loss of fat-free mass (FFM) is one of
      the main systemic effects of chronic obstructive pulmonary disease (COPD). The
      diaphragm is also involved, leading to disadvantageous conditions and poor
      contractile capacities. OBJECTIVES: We measured the thickness of the diaphragm
      (TD) by ultrasonography to evaluate the relationships between echographic
      measurements, parameters of respiratory function and body composition data.
      METHODS: Thirty-two patients (23 males) underwent (1) pulmonary function tests,
      (2) echographic assessment of TD in the zone of apposition at various lung
      volumes, i.e. TD at residual volume (TDRV), TD at functional residual capacity
      (TDFRC) and TD at total lung capacity (TDTLC), and (3) bioelectrical body
      impedance analysis. The BMI and the BODE (BMI-Obstruction-Dyspnea-Exercise) index
      values were reported. RESULTS: TDRV, TDFRC and TDTLC measured 3.3, 3.6 and 6 mm,
      respectively, with good intraobserver reproducibility (0.97, 0.97 and 0.96,
      respectively). All the TDs were found to be related to FFM, with the relationship
      being greater for TDFRC (r(2) = 0.39 and p = 0.0002). With regard to lung
      volumes, inspiratory capacity (IC) was found to be closely related to TDTLC (r(2)
      = 0.42 and p = 0.0001). The difference between TDTLC and TDRV, as a thickening
      value (TDTLCRV), was closely related to FVC (r(2) = 0.34 and p = 0.0004) and to
      air-trapping indices (RV/TLC, FRC/TLC and IC/TLC): the degree of lung
      hyperinflation was greater and the TDTLCRV was less. Finally, we found a
      progressive reduction of both thicknesses and thickenings as the severity of
      IC/TLC increased, with a significant p value for the trend in both analyses (p =
      0.02). CONCLUSIONS: Ultrasonographic assessment of the diaphragm could be a
      useful tool for studying disease progression in COPD patients, in terms of lung
      hyperinflation and the loss of FFM. (c) 2014 S. Karger AG, Basel.

PMID- 24732296
TI  - Food protein-induced enterocolitis syndrome from the parent perspective.
AB  - PURPOSE OF REVIEW: To describe the obstacles that parents face when caring for a
      child with food protein-induced enterocolitis syndrome (FPIES) and discuss
      initiatives of key importance to the FPIES community. RECENT FINDINGS: Findings
      from a previous survey indicate that 80% of pediatricians have little or no
      knowledge of FPIES, suggesting that awareness is severely lacking among frontline
      providers. A preliminary study also indicates that the condition can have a
      profound effect on quality of life for patients and families. SUMMARY: FPIES is a
      rare but growing condition that poses significant personal and familial
      challenges for parents before and after diagnosis. Increased efforts from the
      medical community are needed to raise awareness among medical providers,
      establish improved criteria and guidelines for diagnosis and management, increase
      understanding through research, and offer parent information and support at every
      stage.

PMID- 24732297
TI  - Comparison of M.I.C.E. and Etest with CLSI agar dilution for antimicrobial
      susceptibility testing against oxacillin-resistant Staphylococcus spp.
AB  - OBJECTIVE: The main objective of this study was to comparatively evaluate the
      performance of M.I.C.E. and Etest methodologies to that of agar dilution for
      determining the antimicrobial susceptibility profile of oxacillin-resistant
      Staphylococcus spp. METHODS: A total of 100 oxacillin-resistant Staphylococcus
      spp. isolates were collected from hospitalized patients at a teaching hospital.
      Antimicrobial susceptibility testing for vancomycin, teicoplanin and linezolid
      was performed using the reference CLSI agar dilution method (2009), Etest and
      M.I.C.E. methodologies. The MIC values were interpreted according to CLSI
      susceptibility breakpoints and compared by regression analysis. RESULTS: In
      general, the essential agreement (+/-1-log2) between M.I.C.E. and CLSI agar
      dilution was 93.0%, 84.0% and 77.0% for linezolid, teicoplanin and vancomycin,
      respectively. Essential agreement rates between M.I.C.E. and Etest were excellent
      (>90.0%) for all antibiotics tested. Both strips (M.I.C.E. and Etest) yielded two
      very major errors for linezolid. Unacceptable minor rates were observed for
      teicoplanin against CoNS and for vancomycin against S. aureus. CONCLUSIONS:
      According to our results, linezolid and teicoplanin MICs against all
      staphylococci and S. aureus, respectively, were more accurately predicted by
      M.I.C.E. strips. However, the Etest showed better performance than M.I.C.E. for
      predicting vancomycin MICs against all staphylococci. Thus, microbiologists must
      be aware of the different performance of commercially available gradient strips
      against staphylococci.

PMID- 24732298
TI  - Syncope and electroencephalography.

PMID- 24732300
TI  - Dendritic cell maturation in HCV infection: altered regulation of MHC class I
      antigen processing-presenting machinery.
AB  - BACKGROUND & AIMS: Modulation of dendritic cell (DC) function has been theorized
      as one of the mechanisms used by hepatitis C virus (HCV) to evade the host immune
      response and cause persistent infection. METHODS: We used a range of cell and
      molecular biology techniques to study DC subsets from uninfected and HCV-infected
      individuals. RESULTS: We found that patients with persistent HCV infection have
      lower numbers of circulating myeloid DC and plasmacytoid DC than healthy controls
      or patients who spontaneously recovered from HCV infection. Nonetheless, DC from
      patients with persistent HCV infection display normal phagocytic activity,
      typical expression of the class I and II HLA and co-stimulatory molecules, and
      conventional cytokine production when stimulated to mature in vitro. In contrast,
      they do not display the strong switch from immunoproteasome to standard
      proteasome subunit expression and the upregulation of the transporter-associated
      proteins following stimulation, which were instead observed in DC from uninfected
      individuals. This different modulation of components of the HLA class I antigen
      processing-presenting machinery results in a differential ability to present a
      CD8(+) T cell epitope whose generation is dependent on the LMP7 immunoproteasome
      subunit. CONCLUSIONS: Overall, these findings establish that under conditions of
      persistent HCV antigenemia, HLA class I antigen processing and presentation are
      distinctively regulated during DC maturation.

PMID- 24732301
TI  - The C1B domains of novel PKCepsilon and PKCeta have a higher membrane binding
      affinity than those of the also novel PKCdelta and PKCtheta.
AB  - The C1 domains of novel PKCs mediate the diacylglycerol-dependent translocation
      of these enzymes. The four different C1B domains of novel PKCs (delta, epsilon,
      theta and eta) were studied, together with different lipid mixtures containing
      acidic phospholipids and diacylglycerol or phorbol ester. The results show that
      either in the presence or in the absence of diacylglycerol, C1Bepsilon and C1Beta
      exhibit a substantially higher propensity to bind to vesicles containing
      negatively charged phospholipids than C1Bdelta and C1Btheta. The observed
      differences between the C1B domains of novel PKCs (in two groups of two each)
      were also evident in RBL-2H3 cells and it was found that, as with model
      membranes, in which C1Bepsilon and C1Beta could be translocated to membranes by
      the addition of a soluble phosphatidic acid without diacylglycerol or phorbol
      ester, C1Bdelta and C1Btheta were not translocated when soluble phosphatidic acid
      was added, and diacylglycerol was required to achieve a detectable binding to
      cell membranes. It is concluded that two different subfamilies of novel PKCs can
      be established with respect to their propensity to bind to the cell membrane and
      that these peculiarities in recognizing lipids may explain why these isoenzymes
      are specialized in responding to different triggering signals and bind to
      different cell membranes. 

PMID- 24732302
TI  - Correlation between both morphologic and functional changes and anxiety in
      Alzheimer's disease.
AB  - INTRODUCTION: Although anxiety symptoms are often observed in Alzheimer's disease
      (AD), little attention has been paid to this symptom compared with other
      neuropsychiatric symptoms. METHODS: Twenty-six patients with mild AD underwent
      both magnetic resonance imaging and single photon emission tomography with
      technetium-99m ethyl cysteinate dimer. Neuropsychiatric symptoms were evaluated
      using the Behavioral Pathology in Alzheimer's Disease Scale (Behave-AD). We
      investigated the relationship between anxiety and neuroimaging using Statistical
      Parametric Mapping 8 software. RESULTS: The Behave-AD anxiety score was
      correlated with hyperperfusion in the bilateral anterior cingulate cortices and a
      reduction in the gray matter volume in the right precuneus and inferior parietal
      lobule. CONCLUSION: Our results suggest that anxiety in AD could overlap with the
      neural correlates of anxiety disorders, and that the specific degeneration
      associated with AD might be associated with anxiety.

PMID- 24732303
TI  - Diabetes and obesity are significant risk factors for morning hypertension: from
      Ibaraki Hypertension Assessment Trial (I-HAT).
AB  - AIMS: Although morning hypertension (HT) has been identified as a major
      cardiovascular risk, susceptible populations remain unknown. This study aimed to
      clarify the relationship between morning HT and diabetes or obesity in a large
      scale population. MAIN METHODS: Clinic blood pressure (BP) and BP upon awakening
      were recorded in 2554 outpatients with HT who attended 101 clinics or hospitals
      for two weeks. Mean clinic and awakening BP>140/90 and >135/85 mmHg,
      respectively, were considered as HT. The patients were classified according to
      values for clinic and home BP, into normal BP, white coat HT, masked HT, and
      sustained HT. KEY FINDINGS: Morning BP (mmHg) significantly and progressively
      elevated in the order of normal glucose tolerance, impaired glucose tolerance and
      diabetes (134.1 +/- 12.2, 135.4 +/- 13.1 and 137.5 +/- 11.5; p<0.0001). The
      incidence of morning HT significantly increased and progressively in the same
      order (53.4%, 55.6%, 66.4%, p<0.0001). Morning BP was significantly higher among
      obese patients with diabetes than among non-obese and non-diabetic patients
      (138.8 +/- 10.5, 133.1 +/- 11.9, p<0.0001). In addition, the incidence of morning
      HT was significantly higher in obese diabetic patients than in non-obese and non
      diabetic patients (73.0% vs. 49.9%, p<0.0001). SIGNIFICANCE: Diabetic or obese
      patients frequently have morning HT.

PMID- 24732304
TI  - Tensile behavior and dynamic mechanical analysis of novel poly(lactide/delta
      valerolactone) statistical copolymers.
AB  - Lactide-co-delta-valerolactone copolymers (PLVL) have not attracted as much
      research interest as the more popular poly(lactide-co-epsilon-caprolactone)
      (PLCL) elastomeric materials. In this work the study of the mechanical
      performance is focused on the former with the aim of identifying the potential
      advantages of these thermoplastic elastomers for their application in the
      biomedical field. Mechanical testing (at 21 degrees C and at 37 degrees C) of at
      least 5 specimens and dynamic mechanical analysis (DMA) in duplicate were carried
      out on various PLVL, which include a moderately blocky l-lactide/delta
      valerolactone copolymer (~70% of l-LA and R=0.68) and several that showed a
      random distribution of sequences (R~1): some terpolymers based on l-lactide, d
      lactide and delta-valerolactone (with a lactone content of ~25 and ~14%) and a
      series of copolymers of l-LA and delta-VL having l-LA molar contents ranging from
      69 to 74%. In view of the results, it can be concluded that noteworthy
      improvements in stiffness and strength were achieved by adding delta-VL to the
      reaction mix instead of epsilon-CL, although both monomers have analogous
      chemical properties. For example, a PLVL with a 75:25M composition of l-LA/delta
      VL at 21 degrees C presented a secant modulus of 213.7+/-36.5MPa and
      sigmau=14.7+/-1.4MPa whereas a previously studied PLCL of equal composition had a
      secant modulus and an ultimate stress value of 19.4+/-1.3MPa and 3.2+/-0.6MPa,
      respectively. At 37 degrees C, the differences in the mechanical properties
      between the different PLVLs of this work were far less relevant, with most of
      them showing a fully elastomeric behavior. Referring to the DMA measurements, the
      reduction in the peak of tan delta (from ~2.5 to 0.5) through the glass
      transition was a clear indicator that crystalline domains formed during
      hydrolytic degradation in some of the polymers. However, the more amorphous PLVLs
      with short l-LA average sequence lengths (ll-LA<2.91) did not undergo changes in
      the storage modulus and tan delta curves after two weeks submerged in PBS at 37
      degrees C. 

PMID- 24732306
TI  - New therapeutic options for patients with sepsis and disseminated intravascular
      coagulation.
AB  - The severity of sepsis increases along with the degree of coagulation disorder,
      and a fulminant coagulation abnormality is recognized as disseminated
      intravascular coagulation (DIC). The mortality in sepsis-associated DIC remains
      as high as 40%, which is comparable to that in septic shock. Even though
      intensive research is ongoing, there is currently no established therapy for this
      life-threatening complication. Heparins are the oldest, most popular, and least
      expensive anticoagulants available; however, their usefulness for the treatment
      of septic DIC has never been proved. Expectations for antithrombin concentrate
      were once high, but high-dose antithrombin failed to demonstrate a survival
      benefit, and global sepsis guidelines no longer recommend its use. Recombinant
      activated protein C was the only recommended anticoagulant for the treatment of
      severe sepsis until 2011, but it was subsequently withdrawn from the world market
      after the failure of the latest clinical trial. Recombinant thrombomodulin is
      newly developed and has been utilized in Japan since 2008; however, its efficacy
      has not yet been proved. As shown above, progress has not been as fast as
      expected, but some new agents are upcoming. The efficacy of anticoagulant therapy
      for septic DIC has long been discussed and aggressively studied, and we have
      finally realized that correcting the coagulation disorder is not sufficient to
      conquer this deadly complication. Since many natural anticoagulants have
      pleiotropic functions, we need to examine these effects and apply them to the
      right target at the right timing. 

PMID- 24732305
TI  - Proteomics of secretory and endocytic organelles in Giardia lamblia.
AB  - Giardia lamblia is a flagellated protozoan enteroparasite transmitted as an
      environmentally resistant cyst. Trophozoites attach to the small intestine of
      vertebrate hosts and proliferate by binary fission. They access nutrients
      directly via uptake of bulk fluid phase material into specialized endocytic
      organelles termed peripheral vesicles (PVs), mainly on the exposed dorsal side.
      When trophozoites reach the G2/M restriction point in the cell cycle they can
      begin another round of cell division or encyst if they encounter specific
      environmental cues. They induce neogenesis of Golgi-like organelles, encystation
      specific vesicles (ESVs), for regulated secretion of cyst wall material. PVs and
      ESVs are highly simplified and thus evolutionary diverged endocytic and exocytic
      organelle systems with key roles in proliferation and transmission to a new host,
      respectively. Both organelle systems physically and functionally intersect at the
      endoplasmic reticulum (ER) which has catabolic as well as anabolic functions.
      However, the unusually high degree of sequence divergence in Giardia rapidly
      exhausts phylogenomic strategies to identify and characterize the molecular
      underpinnings of these streamlined organelles. To define the first proteome of
      ESVs and PVs we used a novel strategy combining flow cytometry-based organelle
      sorting with in silico filtration of mass spectrometry data. From the limited
      size datasets we retrieved many hypothetical but also known organelle-specific
      factors. In contrast to PVs, ESVs appear to maintain a strong physical and
      functional link to the ER including recruitment of ribosomes to organelle
      membranes. Overall the data provide further evidence for the formation of a cyst
      extracellular matrix with minimal complexity. The mass spectrometry proteomics
      data have been deposited to the ProteomeXchange Consortium with the dataset
      identifier PXD000694. 

PMID- 24732307
TI  - Burden of acute gastroenteritis, norovirus and rotavirus in a managed care
      population.
AB  - This study assessed and described the episode rate, duration of illness, and
      health care utilization and costs associated with acute gastroenteritis (AGE),
      norovirus gastroenteritis (NVGE), and rotavirus gastroenteritis (RVGE) in
      physician office, emergency department (ED), and inpatient care settings in the
      United States (US). The retrospective analysis was conducted using an
      administrative insurance claims database (2006-2011). AGE episode rates were
      assessed using medical (ICD-9-CM) codes for AGE; whereas a previously published
      "indirect" method was used in assessing estimated episode rates of NVGE and RVGE.
      We calculated per-patient, per-episode and total costs incurred in three care
      settings for the three diseases over five seasons. For each season, we
      extrapolated the total economic burden associated with the diseases to the US
      population. The overall AGE episode rate in the physician office care setting
      declined by 15% during the study period; whereas the AGE episode rate remained
      stable in the inpatient care setting. AGE-related total costs (inflation
      adjusted) per 100 000 plan members increased by 28% during the 2010-2011 season,
      compared with the 2006-2007 season ($832,849 vs. $1 068 116) primarily due to
      increase in AGE-related inpatient costs. On average, the duration of illness for
      NVGE and RVGE was 1 day longer than the duration of illness for AGE (mean: 2
      days). Nationally, the average AGE-related estimated total cost was $3.88
      billion; NVGE and RVGE each accounted for 7% of this total. The episodes of RVGE
      among pediatric populations have declined; however, NVGE, RVGE and AGE continue
      to pose a substantial burden among managed care enrollees. In conclusion, the
      study further reaffirms that RVGE has continued to decline in pediatric
      population post-launch of the rotavirus vaccination program and provides RVGE-
      and NVGE-related costs and utilization estimates which can serve as a resource
      for researchers and policy makers to conduct cost-effectiveness studies for
      prevention programs.

PMID- 24732308
TI  - Effect of passive leg raising on systemic hemodynamics of pregnant women: a
      dynamic assessment of maternal cardiovascular function at 22-24 weeks of
      gestation.
AB  - OBJECTIVE: To investigate functional hemodynamic response to passive leg raising
      in healthy pregnant women and compare it with non-pregnant controls. MATERIALS
      AND METHODS: This was a prospective cross-sectional study with a case-control
      design. A total of 108 healthy pregnant women at 22-24 weeks of gestation and 54
      non-pregnant women were included. Cardiac function and systemic hemodynamics were
      studied at baseline and 90 seconds after passive leg raising using non-invasive
      impedance cardiography. MAIN OUTCOME MEASURES: Trends and magnitudes of changes
      in impedance cardiography derived parameters of cardiac function and systemic
      hemodynamics caused by passive leg raising, and preload responsiveness defined as
      >10% increase in stroke volume or cardiac output after passive leg raising
      compared to baseline. RESULTS: The hemodynamic parameters in both pregnant and
      non-pregnant women changed significantly during passive leg raising compared to
      baseline, but the magnitude and trend of change was similar in both groups. The
      stroke volume increased both in pregnant (p = 0.042) and non-pregnant (p = 0.018)
      women, whereas the blood pressure and systemic vascular resistance decreased
      (p<0.001) following passive leg raising in both groups. Only 14.8% of pregnant
      women and 18.5% of non-pregnant women were preload responsive and the difference
      between groups was not significant (p = 0.705). CONCLUSION: Static measures of
      cardiovascular status are different between healthy pregnant and non-pregnant
      women, but the physiological response to passive leg raising is similar and not
      modified by pregnancy at 22-24 weeks of gestation. Whether physiological response
      to passive leg raising is different in earlier and later stages of pregnancy
      merit further investigation.

PMID- 24732309
TI  - Thrombocytopenia is associated with acute respiratory distress syndrome
      mortality: an international study.
AB  - BACKGROUND: Early detection of the Acute Respiratory Distress Syndrome (ARDS) has
      the potential to improve the prognosis of critically ill patients admitted to the
      intensive care unit (ICU). However, no reliable biomarkers are currently
      available for accurate early detection of ARDS in patients with predisposing
      conditions. OBJECTIVES: This study examined risk factors and biomarkers for ARDS
      development and mortality in two prospective cohort studies. METHODS: We examined
      clinical risk factors for ARDS in a cohort of 178 patients in Beijing, China who
      were admitted to the ICU and were at high risk for ARDS. Identified biomarkers
      were then replicated in a second cohort of1,878 patients in Boston, USA. RESULTS:
      Of 178 patients recruited from participating hospitals in Beijing, 75 developed
      ARDS. After multivariate adjustment, sepsis (odds ratio [OR]:5.58, 95% CI: 1.70
      18.3), pulmonary injury (OR: 3.22; 95% CI: 1.60-6.47), and thrombocytopenia,
      defined as platelet count <80*10(3)/uL, (OR: 2.67; 95% CI: 1.27-5.62)were
      significantly associated with increased risk of developing ARDS. Thrombocytopenia
      was also associated with increased mortality in patients who developed ARDS
      (adjusted hazard ratio [AHR]: 1.38, 95% CI: 1.07-1.57) but not in those who did
      not develop ARDS(AHR: 1.25, 95% CI: 0.96-1.62). The presence of both
      thrombocytopenia and ARDS substantially increased 60-day mortality. Sensitivity
      analyses showed that a platelet count of <100*10(3)/uL in combination with ARDS
      provide the highest prognostic value for mortality. These associations were
      replicated in the cohort of US patients. CONCLUSIONS: This study of ICU patients
      in both China and US showed that thrombocytopenia is associated with an increased
      risk of ARDS and platelet count in combination with ARDS had a high predictive
      value for patient mortality.

PMID- 24732311
TI  - Expression of mitochondrial superoxide dismutase in polymorphonuclear leukocytes
      from patients with type 1 diabetes with and without microvascular complications.
AB  - INTRODUCTION: One of the causes of impaired antioxidant response in patients with
      type 1 diabetes might be decreased expression of mitochondrial manganese
      superoxide dismutase (MnSOD). OBJECTIVES: The aim of this study was to evaluate
      the expression of MnSOD on transcript and protein levels in polymorphonuclear
      leukocytes (PMNLs) from patients with type 1 diabetes and analyze its association
      with microvascular complications. PATIENTS AND METHODS: The MnSOD expression was
      assessed in PMNLs from 46 patients with type 1 diabetes and 12 age- and sex 
      matched healthy subjects. The study group was divided into 2 subgroups: with and
      without microvascular complications. The MnSOD expression on the transcript level
      was evaluated by real -time quantitative polymerase chain reaction, while that on
      the protein level by Western blot analysis. RESULTS: A significant increase in
      the MnSOD transcript level was observed in all patients with diabetes with and
      without microvascular complications (P = 0.01, P = 0.02, respectively). The MnSOD
      protein level was higher in patients without microvascular complications compared
      with those with complications and the control group (P = 0.05, P = 0.03,
      respectively). The MnSOD expression was positively correlated with fasting plasma
      glucose and total cholesterol levels both at the transcript level (r = 0.4, P
      <0.05 for both correlations) and at the protein level (r = 0.3 and r = 0.4,
      respectively, P <0.05). CONCLUSIONS: Although an increased MnSOD transcript level
      in patients with type 1 diabetes suggests enhanced antioxidant mobilization in
      all diabetic patients, decreased levels of the MnSOD protein in PMNLs from
      patients with microvascular complications compared with those without
      complications indicates that patients with microvascular complications may have
      impaired antioxidant response.

PMID- 24732310
TI  - The role of Candida albicans SPT20 in filamentation, biofilm formation and
      pathogenesis.
AB  - Candida albicans is a ubiquitous fungus, which can cause very serious and
      sometimes life-threatening infections in susceptible patients. We used
      Caenorhabditis elegans as a model host to screen a library of C. albicans mutants
      for decreased virulence and identified SPT20 as important for virulence. The
      transcription co-activator SPT20 was identified originally as a suppressor of Ty
      and solo delta insertion mutations, which can cause transcription defects in
      Saccharomyces cerevisiae. It is resistant to the toxicity caused by
      overexpression of GAL4-VP16. We constructed a C. albicans spt20Delta/Delta mutant
      and found the spt20Delta/Delta strain was significantly less virulent than the
      wild-type strain SC5314 in C. elegans (p < 0.0001), Galleria mellonella (p <
      0.01) and mice (p < 0.001). Morphologically, spt20Delta/Delta mutant cells
      demonstrated a "snow-flake" shape and clustered together; prolonged culture times
      resulted in increased size of the cluster. The clustered morphology was
      associated with defects in nuclei distribution, as the nuclei were not observed
      in many cellular compartments. In addition, the C. albicans spt20Delta/Delta
      mutant resulted in defects in hyphae and biofilm formation (compared to the wild
      type strain, p < 0.05), and sensitivity to cell wall and osmotic stressors, and
      to antifungal agents. Thus our study demonstrated a role of C. albicans SPT20 in
      overall morphology and distribution of nuclear material, which may cause the
      defects in filamentation and biofilm formation directly when this gene is
      deleted. 

PMID- 24732312
TI  - Relationship between interleukin-10 -1082A/G polymorphism and risk of ischemic
      stroke: a meta-analysis.
AB  - OBJECTIVE: To analyze the association between -1082A/G polymorphism in
      interleukin-10 (IL-10) gene and ischemic stroke (IS) risk by meta-analysis.
      METHODS: We carried out a systematic electronic search in PubMed, BIOSIS
      Previews, Science Direct, Chinese National Knowledge Infrastructure, Chinese
      Biomedical Database, Weipu database and WANGFANG Database. Pooled odds ratios
      (ORs) with 95% confidence intervals (95%CIs) were calculated to assess the
      strength of the association. RESULTS: 7 studies were included. There was no
      significant association between IL-10 -1082A/G polymorphism and IS risk under all
      genetic models in overall estimates (A vs. G: OR = 1.23,95%CI = 0.85-1.79;AA vs.
      GG: OR = 1.01,95%CI = 0.47-2.19; AG vs. GG: OR = 0.76, 95%CI = 0.38-1.55; AA+AG
      vs. GG: OR = 0.89,95%CI = 0.46-1.73; AA vs. AG+GG: OR = 1.39, 95%CI = 0.91-2.13).
      Similarly, no associations were found in subgroup analysis based on ethnicity and
      source of controls. However, removing the study deviating from Hardy-Weinberg
      equilibrium (HWE) produced statistically significant associations for overall
      estimates under recessive model(AA VS. AG+GG OR 1.58, 95% CI 1.04-2.42) and among
      Asians in all genetic models (A VS.G OR 1.64, 95% CI 1.07-2.53; AA vs. GG OR1.91,
      95% CI 1.31-2.80; AG vs. GG OR1.44, 95% CI 1.09-1.91; AA+AG vs. GG OR 1.54, 95%
      CI 1.18-2.01;AA VS. AG+GG OR 1.79, 95% CI 1.07-3.00). Even after Bonferroni
      correction, the associations were observed still significantly in Asians under
      the two models (AA vs. GG OR1.91, 95% CI 1.31-2.80, P = 0.0008; AA+AG vs. GG OR
      1.54, 95% CI 1.18-2.01, P = 0.001). CONCLUSION: This meta-analysis indicates that
      IL10 -1082 A/G polymorphism is associated with IS susceptibility in Asians and
      the -1082 A allele may increase risk of IS in Asians. Considering the sample size
      is small and between-study heterogeneity is remarkable, more studies with subtle
      design are warranted in future.

PMID- 24732313
TI  - Induction of dendritic cell maturation in the skin microenvironment by soluble
      factors derived from colon carcinoma.
AB  - Autologous tumor cell-based vaccines provide a wide range of tumor antigens and
      personalized neo-epitopes based on individual tumors' unique antigenic mutanome
      signatures. However, tumor-derived factors may hamper in situ maturation of
      dendritic cells (DC) and thus interfere with the generation of effective anti
      tumor immunity. As the skin is a preferred site for tumor vaccine delivery, we
      investigated the influence of primary colon carcinoma-derived soluble factors on
      the maturation state of migrating DC in a human skin explant model. Primary tumor
      derived supernatants (TDSN) enhanced the phenotypic maturation state of skin
      emigrated DC, resulting in an increased T-cell stimulatory ability in an
      allogeneic mixed leukocyte response. In case of monocyte-derived DC a similar
      TDSN-induced maturation induction was found to entirely depend on cyclooxygenase
      (COX)-regulated prostaglandins. In contrast, the increase in skin-emigrated DC
      maturation was completely prostaglandin-independent, as evidenced by the
      inability of the COX inhibitor indomethacin to abrogate this TDSN-induced effect.
      Although TDSN conditioning affected a drop in IL-12p70 release by the skin
      emigrated DC and induced a predominant Th17/Th22 transcriptional profile in
      subsequently stimulated T-cells, Th cell subset differentiation, as assessed by
      intracellular cytokine expression upon polyclonal priming and re-stimulation, was
      not affected. Comparative analysis of phenotypic and transcriptional profiles
      suggests that the observed maturational effects in skin-derived DC may have been
      induced by tumor-derived GM-CSF. In conclusion, soluble factors derived from
      whole-cell colon tumor vaccines will not negatively impact DC migration and
      maturation in human skin, but rather induce DC maturation that will facilitate
      the priming of a poly-functional Th cell response. 

PMID- 24732314
TI  - From human monocytes to genome-wide binding sites--a protocol for small amounts
      of blood: monocyte isolation/ChIP-protocol/library amplification/genome wide
      computational data analysis.
AB  - Chromatin immunoprecipitation in combination with a genome-wide analysis via high
      throughput sequencing is the state of the art method to gain genome-wide
      representation of histone modification or transcription factor binding profiles.
      However, chromatin immunoprecipitation analysis in the context of human
      experimental samples is limited, especially in the case of blood cells. The
      typically extremely low yields of precipitated DNA are usually not compatible
      with library amplification for next generation sequencing. We developed a highly
      reproducible protocol to present a guideline from the first step of isolating
      monocytes from a blood sample to analyse the distribution of histone
      modifications in a genome-wide manner. CONCLUSION: The protocol describes the
      whole work flow from isolating monocytes from human blood samples followed by a
      high-sensitivity and small-scale chromatin immunoprecipitation assay with
      guidance for generating libraries compatible with next generation sequencing from
      small amounts of immunoprecipitated DNA.

PMID- 24732315
TI  - Location of nonmelanoma skin cancers in patients after kidney transplantation.
AB  - INTRODUCTION: Long -term use of immunosuppressant therapy makes kidney transplant
      recipients particularly susceptible to infections and skin cancers. OBJECTIVES:
      The aim of the study was to evaluate the type and location of nonmelanoma skin
      cancers (NMSCs) in patients after kidney transplantation. PATIENTS AND METHODS:
      The study included 486 patients (296 men and 190 women; mean age, 46.1 +/-13.1
      years) after deceased -donor kidney transplantation, most of whom received triple
      immunosuppressive therapy. Patients underwent skin examination. All suspicious
      lesions were thoroughly described in terms of their type, size, and location.
      Only patients with histologically confirmed malignancy were included in the
      study. RESULTS: Of all 486 patients, 25 were diagnosed with 53 NMSCs, including
      39 basal cell carcinomas, 13 squamous cell carcinomas, and 1 case of Bowen's
      disease. The lesions were observed on the face (n = 34), upper limb (n = 8), neck
      (n = 6), and trunk (n = 5). CONCLUSIONS: Most NMSCs were located on the sun 
      exposed areas, emphasizing the effect of ultraviolet radiation on the
      pathogenesis of skin cancers. The presence of lesions on the skin that had not
      been exposed to the sun indicates that a physical examination of the entire skin
      is necessary.

PMID- 24732317
TI  - Comment on "Eliminating chronic kidney disease... as a diagnosis".

PMID- 24732318
TI  - Comment on "Eliminating chronic kidney disease... as a diagnosis". Authors'
      reply.

PMID- 24732316
TI  - The KRAS-variant and miRNA expression in RTOG endometrial cancer clinical trials
      9708 and 9905.
AB  - OBJECTIVE: To explore the association of a functional germline variant in the 3'
      UTR of KRAS with endometrial cancer risk, as well as the association of microRNA
      (miRNA) signatures and the KRAS-variant with clinical characteristics and
      survival outcomes in two prospective RTOG endometrial cancer trials.
      METHODS/MATERIALS: The association of the KRAS-variant with endometrial cancer
      risk was evaluated by case-control analysis of 467 women with type 1 or 2
      endometrial cancer and 582 age-matched controls. miRNA and DNA were isolated for
      expression profiling and genotyping from tumor specimens of 46 women with type 1
      endometrial cancer enrolled in RTOG trials 9708 and 9905. miRNA expression levels
      and KRAS-variant genotype were correlated with patient and tumor characteristics,
      and survival outcomes were evaluated by variant allele type. RESULTS: The KRAS
      variant was not significantly associated with overall endometrial cancer risk
      (14% controls and 17% type 1 cancers), although was enriched in type 2
      endometrial cancers (24%, p = 0.2). In the combined analysis of RTOG 9708/9905,
      miRNA expression differed by age, presence of lymphovascular invasion and KRAS
      variant status. Overall survival rates at 3 years for patients with the variant
      and wild-type alleles were 100% and 77% (HR 0.3, p = 0.24), respectively,
      favoring the variant. CONCLUSIONS: The KRAS-variant may be a genetic marker of
      risk for type 2 endometrial cancers. In addition, tumor miRNA expression appears
      to be associated with patient age, lymphovascular invasion and the KRAS-variant,
      supporting the hypothesis that altered tumor biology can be measured by miRNA
      expression, and that the KRAS-variant likely impacts endometrial tumor biology.

PMID- 24732319
TI  - Comment on "Venous thrombosis: who should be screened for thrombophilia in
      2014?".

PMID- 24732320
TI  - Comment on "Venous thrombosis: who should be screened for thrombophilia in 2014?"
      Author's reply.

PMID- 24732322
TI  - Brucella melitensis in France: persistence in wildlife and probable spillover
      from Alpine ibex to domestic animals.
AB  - Bovine brucellosis is a major zoonosis, mainly caused by Brucella abortus, more
      rarely by Brucella melitensis. France has been bovine brucellosis officially-free
      since 2005 with no cases reported in domestic/wild ruminants since 2003. In 2012,
      bovine and autochthonous human cases due to B. melitensis biovar 3 (Bmel3)
      occurred in the French Alps. Epidemiological investigations implemented in wild
      and domestic ruminants evidenced a high seroprevalence (>45%) in Alpine ibex
      (Capra ibex); no cases were disclosed in other domestic or wild ruminants, except
      for one isolated case in a chamois (Rupicapra rupicapra). These results raised
      the question of a possible persistence/emergence of Brucella in wildlife. The
      purpose of this study was to assess genetic relationships among the Bmel3 strains
      historically isolated in humans, domestic and wild ruminants in Southeastern
      France, over two decades, by the MLVA-panel2B assay, and to propose a possible
      explanation for the origin of the recent bovine and human infections. Indeed,
      this genotyping strategy proved to be efficient for this microepidemiological
      investigation using an interpretation cut-off established for a fine-scale
      setting. The isolates, from the 2012 domestic/human outbreak harbored an
      identical genotype, confirming a recent and direct contamination from cattle to
      human. Interestingly, they clustered not only with isolates from wildlife in
      2012, but also with local historical domestic isolates, in particular with the
      1999 last bovine case in the same massif. Altogether, our results suggest that
      the recent bovine outbreak could have originated from the Alpine ibex population.
      This is the first report of a B. melitensis spillover from wildlife to domestic
      ruminants and the sustainability of the infection in Alpine ibex. However, this
      wild population, reintroduced in the 1970s in an almost closed massif, might be
      considered as a semi-domestic free-ranging herd. Anthropogenic factors could
      therefore account with the high observed intra-species prevalence. 

PMID- 24732323
TI  - Functional characterization of two structurally novel diacylglycerol
      acyltransferase2 isozymes responsible for the enhanced production of stearate
      rich storage lipid in Candida tropicalis SY005.
AB  - Diacylglycerol acyltransferase (DGAT) activity is an essential enzymatic step in
      the formation of neutral lipid i.e., triacylglycerol in all living cells capable
      of accumulating storage lipid. Previously, we characterized an oleaginous yeast
      Candida tropicalis SY005 that yields storage lipid up to 58% under a specific
      nitrogen-stress condition, when the DGAT-specific transcript is drastically up
      regulated. Here we report the identification, differential expression and
      function of two DGAT2 gene homologues--CtDGAT2a and CtDGAT2b of this C.
      tropicalis. Two protein isoforms are unique with respect to the presence of five
      additional stretches of amino acids, besides possessing three highly conserved
      motifs known in other reported DGAT2 enzymes. Moreover, the CtDGAT2a and CtDGAT2b
      are characteristically different in amino acid sequences and predicted protein
      structures. The CtDGAT2b isozyme was found to be catalytically 12.5% more
      efficient than CtDGAT2a for triacylglycerol production in a heterologous yeast
      system i.e., Saccharomyces cerevisiae quadruple mutant strain H1246 that is
      inherently defective in neutral lipid biosynthesis. The CtDGAT2b activity rescued
      the growth of transformed S. cerevisiae mutant cells, which are usually non
      viable in the medium containing free fatty acids by incorporating them into
      triacylglycerol, and displayed preferential specificity towards saturated acyl
      species as substrate. Furthermore, we document that the efficiency of
      triacylglycerol production by CtDGAT2b is differentially affected by deletion,
      insertion or replacement of amino acids in five regions exclusively present in
      two CtDGAT2 isozymes. Taken together, our study characterizes two structurally
      novel DGAT2 isozymes, which are accountable for the enhanced production of
      storage lipid enriched with saturated fatty acids inherently in C. tropicalis
      SY005 strain as well as in transformed S. cerevisiae neutral lipid-deficient
      mutant cells. These two genes certainly will be useful for further investigation
      on the novel structure-function relationship of DGAT repertoire, and also in
      metabolic engineering for the enhanced production of lipid feedstock in other
      organisms.

PMID- 24732324
TI  - Importance of saprotrophic freshwater fungi for pollen degradation.
AB  - Fungi and bacteria are the major organic matter (OM) decomposers in aquatic
      ecosystems. While bacteria are regarded as primary mineralizers in the pelagic
      zone of lakes and oceans, fungi dominate OM decomposition in streams and
      wetlands. Recent findings indicate that fungal communities are also active in
      lakes, but little is known about their diversity and interactions with bacteria.
      Therefore, the decomposer niche overlap of saprotrophic fungi and bacteria was
      studied on pollen (as a seasonally recurring source of fine particulate OM) by
      performing microcosm experiments with three different lake types. Special
      emphasis was placed on analysis of fungal community composition and diversity. We
      hypothesized that (I) pollen select for small saprotrophic fungi and at the same
      time for typical particle-associated bacteria; (II) fungal communities form
      specific free-living and attached sub-communities in each lake type; (III) the
      ratio between fungi or bacteria on pollen is controlled by the lake's chemistry.
      Bacteria-to-fungi ratios were determined by quantitative PCR (qPCR), and
      bacterial and fungal diversity were studied by clone libraries and denaturing
      gradient gel electrophoresis (DGGE) fingerprints. A protease assay was used to
      identify functional differences between treatments. For generalization,
      systematic differences in bacteria-to-fungi ratios were analyzed with a dataset
      from the nearby Baltic Sea rivers. High abundances of Chytridiomycota as well as
      occurrences of Cryptomycota and yeast-like fungi confirm the decomposer niche
      overlap of saprotrophic fungi and bacteria on pollen. As hypothesized, microbial
      communities consistently differed between the lake types and exhibited functional
      differences. Bacteria-to-fungi ratios correlated well with parameters such as
      organic carbon and pH. The importance of dissolved organic carbon and nitrogen
      for bacteria-to-fungi ratios was supported by the Baltic Sea river dataset. Our
      findings highlight the fact that carbon-to-nitrogen ratios may also control
      fungal contributions to OM decomposition in aquatic ecosystems. 

PMID- 24732326
TI  - The International Societies for Investigative Dermatology: the realization of a
      vision for unity and collaboration in the advancement of investigative
      dermatology and cutaneous biology.

PMID- 24732325
TI  - A dose-ranging study in older adults to compare the safety and immunogenicity
      profiles of MF59(r)-adjuvanted and non-adjuvanted seasonal influenza vaccines
      following intradermal and intramuscular administration.
AB  - Strategies to optimize responses to seasonal influenza vaccination in older
      adults include the use of adjuvants, higher antigen doses, and intradermal
      delivery. In this study adults aged >=65 years (n = 450) received a single dose
      of 1 of 2 non-adjuvanted trivalent influenza vaccine (TIV) formulations
      administered intradermally (ID), both containing 6 ug of A/H1N1 and B, differing
      in A/H3N2 content (6 ug or 12 ug), or a single dose of 1 of 8 TIV formulations
      administered intramuscularly (IM) all containing 15 ug of A/H1N1 and B, differing
      in A/H3N2 hemagglutinin (HA) content (15 ug or 30 ug) and/or in MF59((r))
      adjuvant content (0%, 25%, 50%, or 100% of the standard dose). This paper focuses
      on the comparisons of low-dose non-adjuvanted ID, full-dose non-adjuvanted IM and
      full-dose MF59-adjuvanted IM formulations (n = 270). At day 22 post-vaccination,
      at least one European licensure immunogenicity criterion was met by all groups
      against all 3 strains; however, all three criteria were met against all 3 vaccine
      strains by the low-dose non-adjuvanted ID and the full-dose MF59-adjuvanted IM
      groups only. The full-dose MF59-adjuvanted IM group elicited significantly higher
      immune response vs. the low-dose non-adjuvanted ID formulations for most
      comparisons. The full-dose MF59 adjuvanted IM groups were associated with
      increased pain at the site of injection (P<0.01) compared to the ID groups, and
      the low-dose non-adjuvanted ID groups were associated with increased erythema,
      induration, and swelling at the injection site (P<0.0001) and unsolicited AEs
      compared with the IM groups. There were no differences between IM and ID groups
      in the frequencies of subjects experiencing solicited systemic reactions.
      Overall, while MF59 adjuvantation increased pain at the site of injection, and
      intradermal delivery increased unsolicited adverse events, erythema, induration,
      and swelling at the injection site, both strategies of vaccination strongly
      enhanced the immunogenicity of seasonal influenza vaccine in older adults
      compared with conventional non-adjuvanted intramuscular delivery. TRIAL
      REGISTRATION: http://www.clinicaltrials.gov: NCT00848848.

PMID- 24732327
TI  - Unity in action.

PMID- 24732330
TI  - George W. Hambrick Jr (1922-2013).

PMID- 24732331
TI  - A new component of the Fraser complex.
AB  - In embryos, the Fraser complex (FC) mediates epithelial-connective tissue
      interactions. Loss of expression of FC components leads to Fraser syndrome (FS),
      in which cohesion of epithelial tissues and stroma is perturbed. Using zebrafish,
      Richardson et al. (this issue) identified the protein AMACO in the FC. We discuss
      the utility of zebrafish in determining FC functions and identifying FS targets. 

PMID- 24732332
TI  - Cytokine regulation during epidermal differentiation and barrier formation.
AB  - The role of structural components and cell adhesion molecules in the epidermis
      has not been fully studied in terms of the pathophysiology of atopic dermatitis
      (AD). In this issue, Omori-Miyake et al. (2014) report that IL-4 and IL-13, which
      are Th2 cytokines, downregulate the expression of keratins and desmosomal
      cadherins in a STAT6-dependent manner, leading to keratinocyte fragility in the
      face of mechanical stress. Th2 cytokine-induced instability of the epidermis may
      be considered to be one of the pathogenic mechanisms that have roles in AD. 

PMID- 24732333
TI  - Dormant melanomas or changing nevi?
AB  - The development of new primary melanomas in patients treated with vemurafenib has
      been reported recently in a study by Perier-Muzet et al. The primary outcome of
      the study was to describe the dermoscopic changes that prompted excision of those
      melanomas. However, the crucial point raised by the study is the large number of
      melanomas that were detected. 

PMID- 24732334
TI  - Indomethacin to the rescue of TRAIL-resistant melanomas.
AB  - Patients with melanomas develop resistance to both conventional- and targeted
      therapy drugs. Promising clinical responses with immune checkpoint reagents have
      resulted in renewed interest in the use of biological therapies, although only
      subsets of individuals are known to respond to these reagents. Tse et al. now
      report on the use of indomethacin, an anti-inflammatory drug, to sensitize
      therapy-resistant melanoma cells. 

PMID- 24732335
TI  - To B-(RAF) or not to be.
AB  - The identification of targetable mutations has revolutionized the therapy of
      metastatic melanoma. In particular, BRAF and MEK inhibitors have a well
      documented impact on overall survival in metastatic disease. However, therapeutic
      success is highly dependent on the correct identification of these mutations. We
      discuss the impact of molecular heterogeneity in this context. 

PMID- 24732337
TI  - Cells to surgery quiz: May 2014.

PMID- 24732338
TI  - JID VisualDx quiz: May 2014.

PMID- 24732339
TI  - Multivariable analysis.

PMID- 24732340
TI  - Determinants of N-terminal pro-brain natriuretic peptide variation in
      hemodialysis patients and prediction of survival.
AB  - BACKGROUND/AIMS: N-Terminal pro-brain natriuretic peptide (NT-proBNP) is a
      predictor of cardiac events and death in the general population and in chronic
      kidney disease. There is limited information on how natriuretic peptides vary in
      dialysis patients. The aim of this study was to analyze NT-proBNP variability,
      factors predicting its variability and survival related to NT-proBNP variability.
      METHODS: A prospective 3-month observational study of prevalent hemodialysis
      patients with monthly measurements of NT-proBNP was carried out. A total of 211
      hemodialysis patients were included, and mortality was recorded during 52 months
      of follow-up. RESULTS: Inflammation was the strongest predictor of NT-proBNP
      variability. Patients with constantly high NT-proBNP had an increased risk of
      death adjusting for age, sex, dialysis vintage and comorbidity but not when also
      adjusting for nutritional status. CONCLUSIONS: Longitudinal changes in NT-proBNP
      are associated with changes in inflammation, nutritional status, age and
      comorbidity. Due to strong interactions with predictors of mortality such as
      nutritional status, we were unable to confirm NT-proBNP as an independent marker
      for mortality in dialysis patients.

PMID- 24732341
TI  - Combining distance matrices on identical taxon sets for multi-gene analysis with
      singular value decomposition.
AB  - We present a simple and effective method for combining distance matrices from
      multiple genes on identical taxon sets to obtain a single representative distance
      matrix from which to derive a combined-gene phylogenetic tree. The method applies
      singular value decomposition (SVD) to extract the greatest common signal present
      in the distances obtained from each gene. The first right eigenvector of the SVD,
      which corresponds to a weighted average of the distance matrices of all genes,
      can thus be used to derive a representative tree from multiple genes. We apply
      our method to three well known data sets and estimate the uncertainty using
      bootstrap methods. Our results show that this method works well for these three
      data sets and that the uncertainty in these estimates is small. A simulation
      study is conducted to compare the performance of our method with several other
      distance based approaches (namely SDM, SDM* and ACS97), and we find the
      performances of all these approaches are comparable in the consensus setting. The
      computational complexity of our method is similar to that of SDM. Besides
      constructing a representative tree from multiple genes, we also demonstrate how
      the subsequent eigenvalues and eigenvectors may be used to identify if there are
      conflicting signals in the data and which genes might be influential or outliers
      for the estimated combined-gene tree. 

PMID- 24732342
TI  - Use of pyrosequencing to explore the benthic bacterial community structure in a
      river impacted by wastewater treatment plant discharges.
AB  - In this study, we determined the diversity and composition of benthic bacterial
      communities collected in river sediments upstream and downstream from a
      wastewater treatment plant (WWTP). Pyrosequencing of bacterial 16S rRNA genes
      revealed notable differences between the communities from upstream and downstream
      sites. In particular, a higher relative abundance of Acidobacteria, Chloroflexi,
      Deltaproteobacteria and Firmicutes and a lower proportion of Gammaproteobacteria
      and Verrucomicrobia sequences were detected at the downstream site compared to
      the upstream site. These findings represent a first approximation of the impact
      of WWTP discharges on environmental microbial communities. 

PMID- 24732343
TI  - Cardiopulmonary exercise testing to detect chronic thromboembolic pulmonary
      hypertension in patients with normal echocardiography.
AB  - BACKGROUND: Chronic thromboembolic pulmonary hypertension (CTEPH) is a serious
      complication of pulmonary embolism (PE). Taking into account the reported
      incidence of CTEPH after acute PE, the number of patients with undiagnosed CTEPH
      may be high. OBJECTIVES: We aimed to determine if cardiopulmonary exercise
      testing (CPET) could serve as complementary tool in the diagnosis of CTEPH and
      can detect CTEPH in patients with normal echocardiography. METHODS: At diagnosis,
      we analyzed the data of CPET parameters in 42 patients with proven CTEPH and 51
      controls, and evaluated the performance of two scores. RESULTS: VE/VCO2 slope,
      EQO2, EQCO2, P(A-a)O2, end-tidal partial pressure of CO2 at anaerobic threshold
      (PETCO2) and capillary to end-tidal carbon dioxide gradient [P(c-ET)CO2] were
      significantly different between patients with CTEPH and controls (p < 0.001). P(c
      ET)CO2 was the single parameter with the highest sensitivity (85.7%) and
      specificity (88.2%). A score combining VE/VCO2 slope, P(A-a)O2, P(c-ET)CO2,
      PETCO2 [4-parameter-CPET (4-P-CPET) score] reached a sensitivity of 83.3% and a
      specificity of 92.2% after cross-validation. In 42 patients with CTEPH,
      echocardiography identified PH in 29 patients (69%), but it was normal in 13
      patients (31%). All patients with normal or unmeasurable right ventricular
      systolic pressure had a pathological CPET. Twelve of the 13 patients (92%) were
      detected by both CPET scores. CONCLUSION: CPET is a useful noninvasive diagnostic
      tool for the detection of CTEPH in patients with suspected PH but normal
      echocardiography. The 4-P-CPET score provides a high sensitivity with the highest
      specificity.

PMID- 24732345
TI  - The C in TORCH: a cost-effective alternative to screening small-for-gestational
      age infants.
AB  - BACKGROUND: Infants born with birth weights under the 10th percentile for their
      gestational age are classified as small for gestational age (SGA). TORCH
      infections are reported to be associated with SGA infants. With the low incidence
      of infections, screening is likely to be expensive and of low utility. OBJECTIVE:
      The objective of this study was to determine the utility and cost-effectiveness
      of screening SGA infants with TORCH serology titers, urine cytomegalovirus (CMV)
      cultures and cranial ultrasounds. METHODS: A retrospective review was conducted
      on all infants admitted to the neonatal intensive care unit (NICU) at Los Angeles
      County and University of Southern California (LAC+USC) Medical Center from
      January 2003 to December 2011 with a diagnosis of SGA or intrauterine growth
      restriction. Birth characteristics such as birth weight, length, head
      circumference and gestational age were recorded. TORCH titer results, urine CMV
      results and cranial ultrasound findings were collected. RESULTS: Between 2003 and
      2011, 232 SGA infants were admitted to the NICU at LAC+USC Medical Center. Of
      these, 117 infants (50%) had TORCH titer testing performed; there was only 1
      positive CMV IgM and 1 positive HSV IgM result. Repeat urine CMV testing was
      performed on 109 infants (47%), with a total of 296 urine CMV samples collected
      from these infants; 6 infants had positive results, of whom 3 had repeat positive
      urine CMV samples. Overall, 149 of the infants had a cranial ultrasound done,
      none of which were positive for calcifications. CONCLUSIONS: TORCH titer testing,
      urine CMV screening and cranial ultrasound screening are of low yield in
      screening clinically asymptomatic SGA infants for TORCH infections. Given the low
      number of positive results, a cost-effective alternative of selective TORCH
      testing may be limited to infants with additional clinical findings. This study
      serves as a reminder to periodically examine testing practices and patient
      population to maximize cost-effectiveness.

PMID- 24732344
TI  - Activation of DNA damage repair pathways in response to nitrogen mustard-induced
      DNA damage and toxicity in skin keratinocytes.
AB  - Nitrogen mustard (NM), a structural analog of chemical warfare agent sulfur
      mustard (SM), forms adducts and crosslinks with DNA, RNA and proteins. Here we
      studied the mechanism of NM-induced skin toxicity in response to double strand
      breaks (DSBs) resulting in cell cycle arrest to facilitate DNA repair, as a model
      for developing countermeasures against vesicant-induced skin injuries. NM
      exposure of mouse epidermal JB6 cells decreased cell growth and caused S-phase
      arrest. Consistent with these biological outcomes, NM exposure also increased
      comet tail extent moment and the levels of DNA DSB repair molecules phospho H2A.X
      Ser139 and p53 Ser15 indicating NM-induced DNA DSBs. Since DNA DSB repair occurs
      via non homologous end joining pathway (NHEJ) or homologous recombination repair
      (HRR) pathways, next we studied these two pathways and noted their activation as
      defined by an increase in phospho- and total DNA-PK levels, and the formation of
      Rad51 foci, respectively. To further analyze the role of these pathways in the
      cellular response to NM-induced cytotoxicity, NHEJ and HRR were inhibited by DNA
      PK inhibitor NU7026 and Rad51 inhibitor BO2, respectively. Inhibition of NHEJ did
      not sensitize cells to NM-induced decrease in cell growth and cell cycle arrest.
      However, inhibition of the HRR pathway caused a significant increase in cell
      death, and prolonged G2M arrest following NM exposure. Together, our findings,
      indicating that HRR is the key pathway involved in the repair of NM-induced DNA
      DSBs, could be useful in developing new therapeutic strategies against vesicant
      induced skin injury. 

PMID- 24732346
TI  - Effect of erythrocyte aggregation at pathological levels on NO/O2 transport in
      small arterioles.
AB  - This study examined the effects of red blood cell (RBC) aggregation at
      pathological levels on NO/O2 transport in small arterioles. Transient gas
      diffusion simulations were performed with in vivo cell-free layer (CFL) widths
      data obtained from arteriolar flows in the rat cremaster muscle. The CFL data
      were measured at physiological and pathological levels of aggregation under
      reduced flow conditions (pseudoshear rate = 31.4 +/- 10.5 s-1). Our results
      showed that the mean peak NO concentration significantly decreased with
      increasing the aggregation level from non-aggregating to normal-aggregating (P <
      0.05) and to hyper-aggregating (P < 0.01) conditions. In contrast, the partial O2
      pressure (PO2) in pathological aggregating conditions significantly increased
      from those under non-aggregating (P < 0.001) and normal-aggregating (P < 0.05)
      conditions. Although the NO scavenging by RBCs could be impaired with a thicker
      CFL at higher levels of aggregation, the overall decrease in NO production due to
      reduction of wall shear stress with the thicker CFL dominantly limited the NO
      availability in tissue. On the other hand, the O2 availability in tissue
      increased due to the relatively high core hematocrit in the blood lumen with the
      thicker CFL. 

PMID- 24732348
TI  - Long-term mortality in a cohort of home-dwelling elderly with mild Alzheimer's
      disease and Lewy body dementia.
AB  - OBJECTIVE: To study mortality in subjects with mild dementia in Norway with a
      special focus on patients with Lewy body dementia (LBD) compared to Alzheimer's
      disease (AD). METHODS: All referrals of mild dementia patients to dementia
      clinics in western Norway from March 2005 to March 2007 were included and
      followed until December 2012. Diagnoses were based on a comprehensive
      standardized assessment program. RESULTS: Of 209 patients, 137 (66%) had AD and
      53 (25%) had LBD. Dementia was associated with increased mortality (standardized
      mortality ratio = 1.8, AD 1.5, LBD 2.6). The median survival time was 6.2 years
      (95% CI 5.4-6.9). Predictors of mortality were age at diagnosis (HR 1.1 per year)
      and LBD diagnosis (HR 2.4). CONCLUSION: Dementia patients had an increased
      mortality, particularly those with LBD.

PMID- 24732347
TI  - Promotion of atherosclerosis by Helicobacter cinaedi infection that involves
      macrophage-driven proinflammatory responses.
AB  - Helicobacter cinaedi is the most common enterohepatic Helicobacter species that
      causes bacteremia in humans, but its pathogenicity is unclear. Here, we
      investigated the possible association of H. cinaedi with atherosclerosis in vivo
      and in vitro. We found that H. cinaedi infection significantly enhanced
      atherosclerosis in hyperlipidaemic mice. Aortic root lesions in infected mice
      showed increased accumulation of neutrophils and F4/80(+) foam cells, which was
      due, at least partly, to bacteria-mediated increased expression of
      proinflammatory genes. Although infection was asymptomatic, detection of
      cytolethal distending toxin RNA of H. cinaedi indicated aorta infection. H.
      cinaedi infection altered expression of cholesterol receptors and transporters in
      cultured macrophages and caused foam cell formation. Also, infection induced
      differentiation of THP-1 monocytes. These data provide the first evidence of a
      pathogenic role of H. cinaedi in atherosclerosis in experimental models, thereby
      justifying additional investigations of the possible role of enterohepatic
      Helicobacter spp. in atherosclerosis and cardiovascular disease. 

PMID- 24732349
TI  - Button battery intake as foreign body in Chinese children: review of case reports
      and the literature.
AB  - OBJECTIVES: Button batteries have been recognized as one of the dangerous foreign
      bodies to children for more than 30 years, but few related studies have been
      published to give more concern in China. METHODS: We reported 6 cases of button
      battery intake as foreign body in children. The Chinese literature on button
      battery as foreign body in children was reviewed. RESULTS: The interval between
      the accidental ingestion and battery removal ranged from 6 hours to 3 days. Two
      patients had no sequela, 3 patients had tracheoesophageal fistulas, and 1 patient
      had nasal septal perforation. Twenty-eight articles about button battery as
      foreign body in children were obtained by Chinese-language literature searches
      including 25 case reports, 2 health education articles, and 1 imaging article. In
      total, 172 cases of button battery intake as foreign body in children were
      identified, 23 and 10 of the 159 cases involving nasal button battery lodgment
      developed nasal septal perforation and nasal adhesion, respectively.
      Tracheoesophageal fistula was identified in 4 of the 12 ingestion cases. One case
      of button battery intake was in external auditory canal. CONCLUSIONS: A small
      number of children with button battery as foreign body were reported in China,
      which is 1 of the biggest countries with large population of children.

PMID- 24732350
TI  - Hydrodynamic delivery of IL-28B (IFN-lambda3) gene ameliorates lung inflammation
      induced by cigarette smoke exposure in mice.
AB  - Cigarette smoke (CS) is the principal cause of pulmonary inflammatory response.
      IL-28 (IFN-lambda) is a novel group of class II cytokines targeting the
      epithelial cells and IL-28 responses prominent in lungs can exert important
      immunomodulatory effects. We tested the hypothesis that IL-28B may modulate the
      lung inflammation induced by CS. Groups of mice were exposed to CS two times per
      day for 11 consecutive days. CS exposure induced lymphocyte, neutrophil and
      macrophage infiltration and inflammatory cytokine (IL-1beta, tumor necrosis
      factor-alpha (TNF)-alpha, IL-17, and IL-4) in the airways. More importantly, all
      these CS-induced pathogenic changes were significantly inhibited by hydrodynamic
      delivery of plasmid DNA encoding mouse IL-28B. Thus, our results suggest that IL
      28 cytokines are beneficial for the suppression of CS-mediated airway
      inflammation and may be a therapeutic target in CS-related diseases.

PMID- 24732351
TI  - Curcumol suppresses RANKL-induced osteoclast formation by attenuating the JNK
      signaling pathway.
AB  - Osteoclasts, derived from hemopoietic progenitors of the monocyte/macrophage
      lineage, have a unique role in bone resorption, and are considered a potential
      therapeutic target in the treatment of such pathologic bone diseases as
      osteoporosis, rheumatoid arthritis, and periodontitis. In the present study, we
      demonstrate that curcumol, one of the major components of the essential oil of
      Rhizoma Curcumae, exhibits an inhibitory effect on receptor activator of nuclear
      factor kappaB ligand (RANKL)-induced osteoclast differentiation with both bone
      marrow-derived macrophages and RAW264.7 cells in a dose-dependent manner. In
      addition, RANKL-induced mRNA expression of osteoclast-specific genes, such as
      tartrate-resistant acid phosphatase, calcitonin receptor, and cathepsin K, is
      prominently reduced in the presence of curcumol. Furthermore, the molecular
      mechanism of action was investigated, and curcumol inhibited osteoclastogenesis
      by specifically impairing RANKL-induced c-Jun N-terminal kinase (JNK)/activator
      protein-1 (AP-1) signaling, which was further identified in rescue studies by
      means of anisomycin, a JNK signaling-specific activator. Taken together, these
      findings suggest that curcumol suppresses RANKL-induced osteoclast
      differentiation through the JNK/AP-1 signaling pathway, and may be useful as a
      therapeutic treatment for bone resorption-associated diseases. 

PMID- 24732352
TI  - RFP tags for labeling secretory pathway proteins.
AB  - Red fluorescent proteins (RFPs) are useful tools for live cell and multi-color
      imaging in biological studies. However, when labeling proteins in secretory
      pathway, many RFPs are prone to form artificial puncta, which may severely impede
      their further uses. Here we report a fast and easy method to evaluate RFPs fusion
      properties by attaching RFPs to an environment sensitive membrane protein Orai1.
      In addition, we revealed that intracellular artificial puncta are actually
      colocalized with lysosome, thus besides monomeric properties, pKa value of RFPs
      is also a key factor for forming intracellular artificial puncta. In summary, our
      current study provides a useful guide for choosing appropriate RFP for labeling
      secretory membrane proteins. Among RFPs tested, mOrange2 is highly recommended
      based on excellent monomeric property, appropriate pKa and high brightness.

PMID- 24732353
TI  - Overexpression of miR172 suppresses the brassinosteroid signaling defects of bak1
      in Arabidopsis.
AB  - BRI1-Associated Receptor Kinase 1 (BAK1) is a leucine-rich repeat
      serine/threonine receptor-like kinase (LRR-RLK) that is involved in multiple
      developmental pathways, such as brassinosteroid (BR) signaling, plant immunity
      and cell death control in plants. Because the roundish and compact rosette leaves
      of bak1 mutant plants are characteristic phenotypes for deficient BR signaling,
      we screened genetic suppressors of bak1 according to changes in leaf shape to
      identify new components that may be involved in BAK1-mediated BR signaling using
      the activation-tagging method. Here, we report bak1-SUP1, which exhibited longer
      and narrower rosette leaves and an increased BR sensitivity compared with those
      of bak1. Analyses of the T-DNA insertional site and the gene expression that was
      affected by the T-DNA insertion revealed that a microRNA, namely, miR172, over
      accumulates in bak1-SUP1. Detailed phenotypic analyses of bak1-SUP1 and a single
      mutant in which the bak1 mutation was segregated out (miR172-D) revealed that the
      overexpression of miR172 promotes leaf length elongation in adult plants and
      increases the root and hypocotyl growth during the seedling stage compared with
      that of wild type plants. Taken together with its increased BR sensitivity, these
      results suggest that miR172 regulates vegetative growth patterns by modulating BR
      sensitivity as well as by the previously identified developmental phase
      transition.

PMID- 24732354
TI  - Significant decrease of ADP release rate underlies the potent activity of
      dimethylenastron to inhibit mitotic kinesin Eg5 and cancer cell proliferation.
AB  - Eg5 is a mitotic kinesin that plays a crucial role in the formation of bipolar
      mitotic spindles, by hydrolyzing ATP to push apart anti-parallel microtubules.
      Dimethylenastron is potent specific small molecule inhibitor of Eg5. The
      mechanism by which dimethylenastron inhibits Eg5 function remains unclear. By
      comparing with enastron, here we report that dimethylenastron prevents the growth
      of pancreatic and lung cancer cells more effectively, by halting mitotic
      progression and triggering apoptosis. We analyze their interactions with ADP
      bound Eg5 crystal structure, and find that dimethylenastron binds Eg5 motor
      domain with higher affinity. In addition, dimethylenastron allosterically blocks
      the conformational change of the "sandwich"-like ADP-binding pocket more
      effectively. We subsequently use biochemical approach to reveal that
      dimethylenastron slows ADP release more significantly than enastron. These data
      thus provide biological, structural and mechanistic insights into the potent
      inhibitory activity of dimethylenastron.

PMID- 24732355
TI  - Deafness induced by Connexin 26 (GJB2) deficiency is not determined by
      endocochlear potential (EP) reduction but is associated with cochlear
      developmental disorders.
AB  - Connexin 26 (Cx26, GJB2) mutations are the major cause of hereditary deafness and
      are responsible for >50% of nonsyndromic hearing loss. Mouse models show that
      Cx26 deficiency can cause congenital deafness with cochlear developmental
      disorders, hair cell degeneration, and the reduction of endocochlear potential
      (EP) and active cochlear amplification. However, the underlying deafness
      mechanism still remains undetermined. Our previous studies revealed that hair
      cell degeneration is not a primary cause of hearing loss. In this study we
      investigated the role of EP reduction in Cx26 deficiency-induced deafness. We
      found that the EP reduction is not associated with congenital deafness in Cx26
      knockout (KO) mice. The threshold of auditory brainstem response (ABR) in Cx26 KO
      mice was even greater than 110 dB SPL, demonstrating complete hearing loss.
      However, the EP in Cx26 KO mice varied and not completely abolished. In some
      cases, the EP could still remain at higher levels (>70 mV). We further found that
      the deafness in Cx26 KO mice is associated with cochlear developmental disorders.
      Deletion of Cx26 in the cochlea before postnatal day 5 (P5) could cause
      congenital deafness. The cochlea had developmental disorders and the cochlear
      tunnel was not open. However, no congenital deafness was found when Cx26 was
      deleted after P5. The cochlea also displayed normal development and the cochlear
      tunnel was open normally. These data suggest that congenital deafness induced by
      Cx26 deficiency is not determined by EP reduction and may result from cochlear
      developmental disorders.

PMID- 24732356
TI  - Loss of Sprouty4 in T cells ameliorates experimental autoimmune encephalomyelitis
      in mice by negatively regulating IL-1beta receptor expression.
AB  - Th17 cells, which have been implicated in autoimmune diseases, require IL-6 and
      TGF-beta for early differentiation. To gain pathogenicity, however, Th17 cells
      require IL-1beta and IL-23. The underlying mechanism by which these confer
      pathogenicity is not well understood. Here we show that Sprouty4, an inhibitor of
      the PLCgamma-ERK pathway, critically regulates inflammatory Th17 (iTh17) cell
      differentiation. Sprouty4-deficient mice, as well as mice adoptively transferred
      with Sprouty4-deficient T cells, were resistant to experimental autoimmune
      encephalitis (EAE) and showed decreased Th17 cell generation in vivo. In vitro,
      Sprouty4 deficiency did not severely affect TGF-beta/IL-6-induced Th17 cell
      generation but strongly impaired Th17 differentiation induced by IL-1/IL-6/IL-23.
      Analysis of Th17-related gene expression revealed that Sprouty4-deficient Th17
      cells expressed lower levels of IL-1R1 and IL-23R, while RORgammat levels were
      similar. Consistently, overexpression of Sprouty4 or pharmacological inhibition
      of ERK upregulated IL-1R1 expression in primary T cells. Thus, Sprouty4 and ERK
      play a critical role in developing iTh17 cells in Th17 cell-driven autoimmune
      diseases.

PMID- 24732357
TI  - Insights on the antitumor effects of kahweol on human breast cancer: decreased
      survival and increased production of reactive oxygen species and cytotoxicity.
AB  - The present study aims to identify the modulatory effects of kahweol, an
      antioxidant diterpene present in coffee beans, on a panel of human tumor cell
      lines. Kahweol inhibits tumor cell proliferation and clonogenicity and induces
      apoptosis in several kinds of human tumor cells. In the estrogen receptor
      negative MDA-MB231 human breast cancer, the mentioned effects are accompanied by
      caspases 3/7 and 9 activation and cytochrome c release. On the other hand,
      kahweol increases the production of reactive oxygen species and their
      cytotoxicity in human breast cancer cells but not in normal cells. Taken
      together, our data suggest that kahweol is an antitumor compound with inhibitory
      effects on tumor cell growth and survival, especially against MDA-MB231 breast
      cancer cells. 

PMID- 24732358
TI  - Positive association of long telomeres with the invasive capacity of
      hepatocellular carcinoma cells.
AB  - Invasion, the representative feature of malignant tumors, leads to an increase in
      mortality. The malignant liver tumor - hepatocellular carcinoma (HCC) - has an
      enhanced invasive capacity that results in increased patient mortality. Moreover,
      this enhanced invasive capacity is due to the up-regulation of invasion promoters
      such as zinc finger protein SNAI1 (Snail) and matrix metalloproteinases (MMPs),
      and the down-regulation of invasion suppressor molecules such as E-cadherin.
      Telomerase reverse transcriptase (TERT), which encodes the catalytic subunit of
      telomerase, is highly expressed in a variety of invasive cancers, including HCC.
      Telomerase activation induces telomere elongation, thereby leading to cell
      immortalization during malignant tumor progression. However, the relationship
      between telomere length and invasion is yet to be experimentally corroborated. In
      this paper, we revealed that invasive HCC cells passing through the Matrigel
      display significantly longer telomeres than non-invasive HCC cells. Moreover, we
      established a method that can distinguish and sort cells containing long
      telomeres and short telomeres. Using this system, we observed that the HCC cells
      containing long telomeres had a high-level expression of invasion-promoting genes
      and a low-level expression of invasion-suppressing E-cadherin. Furthermore, HCC
      cells containing long telomeres exhibited a higher invasive capacity than HCC
      cells containing short telomeres. Taken together, our findings suggest that long
      telomeres are positively associated with the invasive capacity of HCC cells and
      may be a potent target for malignant liver cancer treatment. 

PMID- 24732359
TI  - S100A4 is frequently overexpressed in lung cancer cells and promotes cell growth
      and cell motility.
AB  - S100A4, a small calcium-binding protein belonging to the S100 protein family, is
      commonly overexpressed in a variety of tumor types and is widely accepted to
      associate with metastasis by regulating the motility and invasiveness of cancer
      cells. However, its biological role in lung carcinogenesis is largely unknown. In
      this study, we found that S100A4 was frequently overexpressed in lung cancer
      cells, irrespective of histological subtype. Then we performed knockdown and
      forced expression of S100A4 in lung cancer cell lines and found that specific
      knockdown of S100A4 effectively suppressed cell proliferation only in lung cancer
      cells with S100A4-overexpression; forced expression of S100A4 accelerated cell
      motility only in S100A4 low-expressing lung cancer cells. PRDM2 and VASH1,
      identified as novel upregulated genes by microarray after specific knockdown of
      S100A4 in pancreatic cancer, were also analyzed, and we found that PRDM2 was
      significantly upregulated after S100A4-knockdown in one of two analyzed S100A4
      overexpressing lung cancer cells. Our present results suggest that S100A4 plays
      an important role in lung carcinogenesis by means of cell proliferation and
      motility by a pathway similar to that in pancreatic cancer.

PMID- 24732360
TI  - Cilostazol induces mitochondrial fatty acid beta-oxidation in C2C12 myotubes.
AB  - Cilostazol is a drug licensed for the treatment of intermittent claudication. Its
      main action is to elevate intracellular levels of cyclic monophosphate (cAMP) by
      inhibiting the activity of type III phosphodiesterase, a cAMP-degrading enzyme.
      The effects of cilostazol on fatty acid oxidation (FAO) are as yet unknown. In
      this study, we report that cilostazol can elevate complete FAO and decrease both
      triacylglycerol (TAG) accumulation and TAG secretion. This use of cilostazol
      treatment increases expression of PGC-1alpha and, subsequently, its target genes,
      such as ERRalpha, NOR1, CD36, CPT1, MCAD, and ACO. Expression of these factors is
      linked to fatty acid beta-oxidation but this effect is inhibited by H-89, a
      specific inhibitor of the PKA/CREB pathway. Importantly, knockdown of PGC-1alpha
      using siRNA abolished the effects of cilostazol in fatty acid oxidation (FAO) and
      TAG metabolism. These findings suggested that the PKA/CREB/PGC-1alpha pathway
      plays a critical role in cilostazol-induced fatty acid oxidation and TAG
      metabolism.

PMID- 24732361
TI  - LPS inhibits caspase 3-dependent apoptosis in RAW264.7 macrophages induced by the
      AMPK activator AICAR.
AB  - AMP-activated kinase is a cellular energy sensor which is activated in stages of
      increased ATP consumption. Its activation has been associated with a number of
      beneficial effects such as decreasing inflammatory processes and the disease
      progress of diabetes and obesity, respectively. Furthermore, AMPK activation has
      been linked with induction of cell cycle arrest and apoptosis in cancer and
      vascular cells, indicating that it might have a therapeutic impact for the
      treatment of cancer and atherosclerosis. However, the impact of AMPK on the
      proliferation of macrophages, which also play a key role in the formation of
      atherosclerotic plaques and in inflammatory processes, has not been focused so
      far. We have assessed the influence of AICAR- and metformin-induced AMPK
      activation on cell viability of macrophages with and without inflammatory
      stimulation, respectively. In cells without inflammatory stimulation, we found a
      strong induction of caspase 3-dependent apoptosis associated with decreased mTOR
      levels and increased expression of p21. Interestingly, these effects could be
      inhibited by co-stimulation with bacterial lipopolysaccharide (LPS) but not by
      other proinflammatory cytokines suggesting that AICAR induces apoptosis via AMPK
      in a TLR4-pathway dependent manner. In conclusion, our results revealed that AMPK
      activation is not only associated with positive effects but might also contribute
      to risk factors by disturbing important features of macrophages. The fact that
      LPS is able to restore AMPK-associated apoptosis might indicate an important role
      of TLR4 agonists in preventing unfavorable cell death of immune cells. 

PMID- 24732362
TI  - Protein phosphatase 1 dephosphorylates Orc2.
AB  - Phosphorylation of Thr(116) and Thr(226) on Orc2, one of the six subunits of the
      origin recognition complex (ORC), by cyclin A/CDK2 during S phase leads to the
      dissociation of Orc2, Orc3, Orc4, and Orc5 subunits (Orc2-5) from human chromatin
      and replication origins. The phosphorylated Orc2 becomes dephosphorylated in the
      late M phase of the cell cycle. Here we show that protein phosphatase 1 (PP1)
      dephosphorylates Orc2. Dephosphorylation of Orc2 was accompanied by associating
      the dissociated Orc subunits with chromatin. Inhibitors of PP1 preferentially
      inhibited the dephosphorylation of Orc2. The overexpression of the alpha, beta
      and gamma PP1 isoforms decreased the amount of phosphorylated Orc2, and the
      depletion of these isoforms by RNA interference increased the amount of
      phosphorylated Orc2. These results suggest that PP1 dephosphorylates Orc2 to
      promote the binding of ORC to chromatin.

PMID- 24732364
TI  - Emerging inhalation aerosol devices and strategies: where are we headed?
AB  - Novel inhaled therapeutics including antibiotics, vaccines and anti
      hypertensives, have led to innovations in designing suitable delivery systems.
      These emerging design technologies are in urgent demand to ensure high
      aerosolisation performance, consistent efficacy and satisfactory patient
      adherence. Recent vibrating-mesh and software technologies have resulted in
      nebulisers that have remarkably accurate dosing and portability. Alternatively,
      dry powder inhalers (DPIs) have become highly favourable for delivering high-dose
      and single-dose drugs with the aid of advanced particle engineering. In contrast,
      innovations are needed to overcome the technical constrains in drug-propellant
      incompatibility and delivering high-dose drugs with pressurised metered dose
      inhalers (pMDIs). This review discusses recent and emerging trends in pulmonary
      drug delivery systems. 

PMID- 24732365
TI  - Multimodal imaging of a transcatheter pacemaker implantation within a reanimated
      human heart.

PMID- 24732363
TI  - Expression profiling of primary and metastatic ovarian tumors reveals differences
      indicative of aggressive disease.
AB  - The behavior and genetics of serous epithelial ovarian cancer (EOC) metastasis,
      the form of the disease lethal to patients, is poorly understood. The unique
      properties of metastases are critical to understand to improve treatments of the
      disease that remains in patients after debulking surgery. We sought to identify
      the genetic and phenotypic landscape of metastatic progression of EOC to
      understand how metastases compare to primary tumors. DNA copy number and mRNA
      expression differences between matched primary human tumors and omental
      metastases, collected at the same time during debulking surgery before
      chemotherapy, were measured using microarrays. qPCR and immunohistochemistry
      validated findings. Pathway analysis of mRNA expression revealed metastatic
      cancer cells are more proliferative and less apoptotic than primary tumors,
      perhaps explaining the aggressive nature of these lesions. Most cases had copy
      number aberrations (CNAs) that differed between primary and metastatic tumors,
      but we did not detect CNAs that are recurrent across cases. A six gene expression
      signature distinguishes primary from metastatic tumors and predicts overall
      survival in independent datasets. The genetic differences between primary and
      metastatic tumors, yet common expression changes, suggest that the major clone in
      metastases is not the same as in primary tumors, but the cancer cells adapt to
      the omentum similarly. Together, these data highlight how ovarian tumors develop
      into a distinct, more aggressive metastatic state that should be considered for
      therapy development. 

PMID- 24732366
TI  - Use of a discrimination algorithm to reduce inappropriate shocks with a
      subcutaneous implantable cardioverter-defibrillator.
AB  - BACKGROUND: The subcutaneous implantable cardioverter-defibrillator system (S
      ICD) uses a novel detection algorithm previously shown to discriminate induced
      tachyarrhythmias (ventricular vs supraventricular) effectively. OBJECTIVE: The
      purpose of this study was to evaluate the role of the S-ICD discrimination
      algorithm in reducing the incidence of spontaneous inappropriate shocks. METHODS:
      A total of 314 subjects underwent implantation with an S-ICD system as part of
      the S-ICD Clinical Investigation (IDE Trial). Subjects were grouped according to
      programming at discharge to either a single shock zone or 2 shock zones, with a
      discrimination algorithm in the lower rate zone. RESULTS: This cohort had 226
      subjects (72%) with dual zone programming and 88 subjects (28%) with single zone
      programming. Over a mean follow-up period of 661 +/- 174 days, inappropriate
      shocks occurred in 23 subjects from the dual zone subgroup (10.2%) and 23
      subjects from the single zone subgroup (26.1%, P < .001), with 2-year
      inappropriate shock-free rates of 89.7% vs. 73.6%;,respectively (hazard ratio
      0.38, P = .001). Freedom from appropriate shocks did not differ between subgroups
      (92.2% vs. 90.3%, hazard ratio 0.82, P = .64). Moreover, mean time to appropriate
      therapy did not differ between subgroups, and there was only 1 episode of
      arrhythmic syncope in the cohort. CONCLUSION: The addition of a second shock zone
      with an active discrimination algorithm was strongly associated with a reduction
      in inappropriate shocks with the S-ICD system and did not result in prolongation
      of detection times or increased syncope. These data support the use of dual zone
      programming as a standard setting for S-ICD patients.

PMID- 24732367
TI  - Troponin elevation after radiofrequency catheter ablation of atrial fibrillation:
      relevance to AF substrate, procedural outcomes, and reverse structural
      remodeling.
AB  - BACKGROUND: Although radiofrequency ablation creates myocardial necrosis leading
      to troponin T (TnT) release into the systemic circulation, the significance of
      TnT elevation after atrial fibrillation (AF) ablation is unknown. OBJECTIVE: To
      demonstrate a possible mechanism of reverse structural remodeling in the left
      atrium (LA) by evaluating postprocedural TnT elevation. METHODS: This study
      included 106 patients with an enlarged LA (paroxysmal AF, n = 43; persistent AF,
      n = 63). All patients underwent pulmonary vein isolation alone in the index
      procedure. Left atrial volume indexed to body surface area (LAVi) was measured by
      echocardiography before ablation and 6 months after sinus rhythm restoration.
      Patients were divided into responders (n = 53) and nonresponders (n = 53) based
      on a cutoff value of 23% reduction in LAVi. The TnT level was measured 12 hours
      postprocedure. RESULTS: LAVi decreased from 43 +/- 13 to 33 +/- 12 mL/m(2) (P <
      .0001). The TnT level was higher in responders than in nonresponders (1.31 +/-
      0.34 MUg/L vs 0.88 +/- 0.29 MUg/L; P < .0001) and correlated linearly with
      percent reduction in LAVi (R = .54; P < .0001). Also in multivariate analysis,
      the TnT level was the only independent predictor for responders (odds ratio 90.1;
      95% confidence interval 14.95-543.3; P < .0001). The TnT level in patients who
      required a repeat procedure (n = 30) was lower than that in patients who did not
      require a repeat procedure only in the persistent AF group (0.92 +/- 0.38 MUg/L
      vs 1.16 +/- 0.37 MUg/L; P = .01). CONCLUSION: Greater elevation of the TnT level
      was related both to favorable outcomes after ablation and to greater reversal of
      structural remodeling. Postprocedural TnT level may be reflective of the
      preservation of healthy LA myocardium.

PMID- 24732368
TI  - A wide QRS tachycardia: what is the mechanism?

PMID- 24732369
TI  - Oral contraceptive use and the risk of cardiac events in patients with long QT
      syndrome.
AB  - BACKGROUND: In prior clinical studies of patients with long QT syndrome (LQTS),
      pregnancy was associated with fewer cardiac events (CEs) compared to before or
      after pregnancy. In recent animal studies involving rabbits with LQTS mutations,
      progesterone had favorable effects on CEs compared to estrogen. The effect of
      oral contraceptive therapy with its high progesterone/estrogen ratio on the risk
      of CEs in patients with LQTS has not been examined. OBJECTIVE: To study the
      effect of oral contraceptive use on the risk of CEs in patients with LQTS.
      METHODS: We studied 174 patients from the Rochester-based LQTS Registry who
      responded to a questionnaire about their oral contraceptive use. We used time
      dependent Cox regression to estimate the hazard ratio for recurrent CEs when
      patients were using vs not using oral contraceptives during nonpregnancy periods.
      For this recurrent events analysis, the Prentice-Williams-Peterson model was used
      and the time origin was defined as the onset of menarche. We adjusted for the
      baseline corrected QT interval, history of CEs before menarche, age at menarche
      onset, number of births, time-dependent beta-blocker therapy, and LQTS genotype.
      RESULTS: No differences in the risk of CEs for the times patients with LQTS were
      using vs not using oral contraceptives was found in the general population with
      LQTS (hazard ratio 1.01; P = .95) or in analyses of LQTS subsets (P > .2).
      CONCLUSION: Oral contraceptive therapy use did not affect LQTS-related CEs in the
      study population. Oral contraceptives did not show beneficial or harmful effects
      in this patient group.

PMID- 24732370
TI  - Incidence of sudden cardiac arrest in high school student athletes on school
      campus.
AB  - BACKGROUND: An accurate estimate of the incidence of sudden cardiac arrest (SCA)
      in high school student athletes is needed to guide prevention strategies.
      OBJECTIVE: To prospectively investigate SCA rates in high school student athletes
      vs student nonathletes. METHODS: A prospective observational study of 2149 US
      high schools participating in the National Registry for AED Use in Sports was
      conducted from August 2009 to July 2011. Schools were contacted quarterly to
      collect and review SCA cases occurring on school campus. Ninety-five percent
      (2045) of the schools confirmed participation for the entire 2-year period.
      RESULTS: The average numbers of total students and student athletes per school
      were 963 and 367, respectively, providing more than 4.1 million total student
      years and more than 1.5 million student athlete-years of surveillance. Twenty-six
      cases of SCA occurred in students, including 18 cases in student athletes-all
      during exercise. The incidence of SCA in all students was 0.63 per 100,000; in
      student athletes, 1.14 per 100,000; and in student nonathletes, 0.31 per 100,000.
      The relative risk of SCA in student athletes vs nonathletes was 3.65 (95%
      confidence interval 1.6-8.4; P < .01). Sixteen of 18 (89%) student athletes with
      SCA were boys, resulting in an incidence of 1.73 per 100,000 in boys and 0.31 per
      100,000 in girls and a relative risk in male compared with female student
      athletes of 5.65 (95% confidence interval 1.3-24.6; P < .01). CONCLUSION: The
      incidence of SCA in high school student athletes is higher than previous
      estimates and may justify more advanced cardiac screening and improved emergency
      planning in schools.

PMID- 24732371
TI  - Renin-angiotensin system gene polymorphisms predict the risk of stroke in
      patients with atrial fibrillation: a 10-year prospective follow-up study.
AB  - BACKGROUND: Little evidence is available regarding the impact of genetic
      polymorphisms on the risk of stroke in patients with atrial fibrillation (AF).
      Angiotensin II plays a pathophysiologic role in prothrombotic atrial endocardial
      remodeling. OBJECTIVE: The purpose of this study was to investigate the effect of
      polymorphisms of renin-angiotensin system genes on the incidence of stroke in a
      prospective cohort of patients with AF. METHODS: A total of 712 AF patients were
      longitudinally followed-up for 10.3 +/- 2.7 years. Eight polymorphisms of renin
      angiotensin system genes were genotyped. RESULTS: Patients carrying the G-6
      allele in the promoter of the angiotensinogen gene, which was associated with
      higher promoter activity, were more likely to develop stroke than were
      noncarriers (hazard ratio 2.54, 95% confidence interval [1.26-5.12], P = .009
      after adjustment for CHADS2 score). G-6A polymorphism provides information
      additional to CHADS2 on stroke risk prediction (C-statistic 0.672 vs. 0.724, P =
      .039). In haplotype analysis, angiotensinogen gene promoter haplotypes containing
      -217G/-6G, which was associated with the highest promoter activity, were
      associated with an increased risk of stroke (P = .004). G-217/G-6 haplotype
      carriers were even more likely to develop stroke than were noncarriers (hazard
      ratio 2.78, 95% confidence interval 1.37-5.64, P = .003 after multivariable
      adjustment). In pharmacogenetic analysis, the increased risk of stroke in
      subjects carrying G-6 was eliminated by concomitant treatment with an angiotensin
      converting enzyme inhibitor or angiotensin II receptor blocker (P = .012 for
      interaction). CONCLUSION: In addition to the CHADS2 score, angiotensinogen gene
      polymorphisms may be considered an additional genetic predictor of stroke in
      patients with AF. Genotyping of the angiotensinogen gene is helpful to determine
      which AF patients may benefit from treatment with an angiotensin-converting
      enzyme inhibitor or angiotensin II receptor blocker.

PMID- 24732372
TI  - Procedural and clinical outcomes after catheter ablation of unstable ventricular
      tachycardia supported by a percutaneous left ventricular assist device.
AB  - BACKGROUND: Hemodynamic support using percutaneous left ventricular assist
      devices (pLVADs) during catheter mapping and ablation of unstable ventricular
      tachycardia (VT) can provide effective end-organ perfusion. However, its effect
      on procedural and clinical outcomes remains unclear. OBJECTIVE: To
      retrospectively evaluate the procedural and clinical outcomes after the catheter
      ablation of unstable VT with and without pLVAD support. METHODS: Sixty-eight
      consecutive unstable, scar-mediated endocardial and/or epicardial VT ablation
      procedures performed in 63 patients were evaluated. During VT mapping and
      ablation, hemodynamic support was provided by intravenous inotropes with a pLVAD
      (n = 34) or without a pLVAD (control; n = 34). RESULTS: Baseline patient
      characteristics were similar. VT was sustained longer with a pLVAD (27.4 +/- 18.7
      minutes) than without a pLVAD (5.3 +/- 3.6 minutes) (P < .001). A higher number
      of VTs were terminated during ablation with a pLVAD (1.2 +/- 0.9 per procedure)
      than without a pLVAD (0.4 +/- 0.6 per procedure) (P < .001). Total radiofrequency
      ablation time was shorter with a pLVAD (53 +/- 30 minutes) than without a pLVAD
      (68 +/- 33 minutes) (P = .022), but with similar procedural success rates (71%
      for both pLVAD and control groups; P = 1.000). Although during 19 +/- 12 months
      of follow-up VT recurrence did not differ between pLVAD (26%) and control (41%)
      groups (P = .305), the composite end point of 30-day rehospitalization, redo-VT
      ablation, recurrent implantable cardioverter-defibrillator therapies, and 3-month
      mortality was lower with a pLVAD (12%) than without a pLVAD (35%) (P = .043).
      CONCLUSION: In this nonrandomized retrospective study, catheter ablation of
      unstable VT supported by a pLVAD was associated with shorter ablation times and
      reduced hospital length of stay. While pLVAD support did not affect VT
      recurrence, it was associated with a lower composite end point of 30-day
      rehospitalization, redo-VT ablation, recurrent implantable cardioverter
      defibrillator therapies, and 3-month mortality.

PMID- 24732373
TI  - Safety of radiofrequency catheter ablation without coronary angiography in aortic
      cusp ventricular arrhythmias.
AB  - BACKGROUND: Ventricular arrhythmias (VAs) originating from the aortic root are
      common. Coronary angiography is typically recommended before catheter ablation to
      document proximity of the ablation catheter to the coronary ostia. OBJECTIVE: To
      investigate how often catheter ablation in the aortic root could be guided by
      phased-array intracardiac echocardiography (ICE) and electroanatomic mapping
      without requiring aortography or coronary angiography. METHODS: We reviewed
      consecutive patients referred for aortic root VAs to operators experienced in the
      use of ICE at a single center. An ICE catheter and a 3.5-mm irrigated ablation
      catheter were used in all cases, and the need for angiography before ablation was
      documented. Acute success and acute and 30-day complications were noted. RESULTS:
      Thirty-five patients (age 58 +/- 13 years; 74% men) were referred for the
      ablation of VAs; 32 of 35 (91%) underwent ablation using ICE and 3-dimensional
      mapping without the need for coronary angiography. Successful acute ablation was
      achieved in 29 of 35 (83%) patients. In all cases, the catheter tip was directly
      visualized with ICE >1 cm from the coronary ostia. The site of origin of the
      earliest VA was the left cusp (17 of 35 [49%]), right cusp (9 of 35 [26%]), right
      left cusp junction (8 of 35 [23%]), or right-noncoronary cusp junction (1 of 35
      [3%]). There were no cases of coronary injury, embolic stroke, aortic root
      perforation, worsening of aortic regurgitation, or death acutely or at 30 days.
      CONCLUSION: Radiofrequency ablation of VAs originating from the aortic root may
      be safely performed using ICE and electroanatomic mapping in the majority of
      cases without the need for coronary angiography.

PMID- 24732374
TI  - Introduction (foreword) to the issue. Heart and lung monitoring.

PMID- 24732375
TI  - Spatial distribution of soil organic carbon and its influencing factors in desert
      grasslands of the Hexi Corridor, northwest China.
AB  - Knowledge of the distribution patterns of soil organic carbon (SOC) and factors
      that influence these patterns is crucial for understanding the carbon cycle. The
      objectives of this study were to determine the spatial distribution pattern of
      soil organic carbon density (SOCD) and the controlling factors in arid desert
      grasslands of northwest China. The above- and belowground biomass and SOCD in 260
      soil profiles from 52 sites over 2.7*10(4) km2 were investigated. Combined with a
      satellite-based dataset of an enhanced vegetation index during 2011-2012 and
      climatic factors at different sites, the relationships between SOCD and biotic
      and abiotic factors were identified. The results indicated that the mean SOCD was
      1.20 (SD:+/- 0.85), 1.73 (SD:+/- 1.20), and 2.69 (SD:+/- 1.91) kg m(-2) at soil
      depths of 0-30 cm, 0-50 cm, and 0-100 cm, respectively, which was smaller than
      other estimates in temperate grassland, steppe, and desert-grassland ecosystems.
      The spatial distribution of SOCD gradually decreased from the southeast to the
      northwest, corresponding to the precipitation gradient. SOCD increased
      significantly with vegetation biomass, annual precipitation, soil moisture, clay
      and silt content, and decreased with mean annual temperature and sand content.
      The correlation between BGB and SOCD was closer than the correlation between AGB
      and SOCD. Variables could together explain about 69.8%, 74.4%, and 78.9% of total
      variation in SOCD at 0-30 cm, 0-50 cm, and 0-100 cm, respectively. In addition,
      we found that mean annual temperature is more important than other abiotic
      factors in determining SOCD in arid desert grasslands in our study area. The
      information obtained in this study provides a basis for accurately estimating SOC
      stocks and assessing carbon (C) sequestration potential in the desert grasslands
      of northwest China.

PMID- 24732377
TI  - Down-regulation of miR-141 induced by helicobacter pylori promotes the invasion
      of gastric cancer by targeting STAT4.
AB  - BACKGROUND: The association between Helicobacter pylori infection and gastric
      cancer has been identified recently. However, the molecular mechanism remained
      largely unknown. METHODS AND RESULTS: We found that miR-141 was decreased in
      Helicobacter pylori positive specimens (n=75) compared with negative tissues
      (n=75). The knockdown of miR-141 enhanced the invasion ability of gastric cancer
      cells; meanwhile, over-expression of miR-141 could inhibit the abilities of
      gastric cancer cells in vitro. A luciferase assay revealed that miR-141 was
      directly bound to the 3'-untranslated regions (3'-UTR) of STAT4. STAT4 was found
      up-regulated at mRNA and protein levels, as shown by qRT-PCR and western blot.
      Over-expression of STAT4 was used to mimic miR-141 action in the invasion of
      gastric cancer. CONCLUSION: MiR-141 may play a pivotal role in controlling
      gastric cancer invasion through regulating STAT4 and maybe a potential target to
      treat gastric cancer.

PMID- 24732378
TI  - Rho-actin signaling to the MRTF coactivators dominates the immediate
      transcriptional response to serum in fibroblasts.
AB  - The transcription factor SRF (serum response factor) recruits two families of
      coactivators, the MRTFs (myocardin-related transcription factors) and the TCFs
      (ternary complex factors), to couple gene transcription to growth factor
      signaling. Here we investigated the role of the SRF network in the immediate
      transcriptional response of fibroblasts to serum stimulation. SRF recruited its
      cofactors in a gene-specific manner, and virtually all MRTF binding was directed
      by SRF. Much of SRF DNA binding was serum-inducible, reflecting a requirement for
      MRTF-SRF complex formation in nucleosome displacement. We identified 960 serum
      responsive SRF target genes, which were mostly MRTF-controlled, as assessed by
      MRTF chromatin immunoprecipitation (ChIP) combined with deep sequencing (ChIP
      seq) and/or sensitivity to MRTF-linked signals. MRTF activation facilitates RNA
      polymerase II (Pol II) recruitment or promoter escape according to gene context.
      MRTF targets encode regulators of the cytoskeleton, transcription, and cell
      growth, underpinning the role of SRF in cytoskeletal dynamics and mechanosensing.
      Finally, we show that specific activation of either MRTFs or TCFs can reset the
      circadian clock. 

PMID- 24732379
TI  - Calcineurin/Nfatc1 signaling links skin stem cell quiescence to hormonal
      signaling during pregnancy and lactation.
AB  - In most tissues, the prevailing view is that stem cell (SC) niches are generated
      by signals from within the nearby tissue environment. Here, we define genetic
      changes altered in hair follicle (HF) SCs in mice treated with a potent SC
      activator, cyclosporine A (CSA), which inhibits the phosphatase calcineurin (CN)
      and the activity of the transcription factor nuclear factor of activated T cells
      c1 (Nfatc1). We show that CN/Nfatc1 regulates expression of prolactin receptor
      (Prlr) and that canonical activation of Prlr and its downstream signaling via
      Jak/Stat5 drives quiescence of HF SCs during pregnancy and lactation, when serum
      prolactin (Prl) levels are highly elevated. Using Prl injections and
      genetic/pharmacological loss-of-function experiments in mice, we show that Prl
      signaling stalls follicular SC activation through its activity in the skin
      epithelium. Our findings define a unique CN-Nfatc1-Prlr-Stat5 molecular circuitry
      that promotes persistent SC quiescence in the skin. 

PMID- 24732382
TI  - Handedness consistency influences bimanual coordination: a behavioural and
      electrophysiological investigation.
AB  - Previous research has shown that handedness consistency might be a more important
      factor than direction of hand dominance in the performance of various cognitive
      and motor tasks. We investigated the effect of handedness consistency in bimanual
      coordination. We employed a task where participants had to respond to visual cues
      and perform symmetrical or asymmetrical bimanual movements towards cue-designated
      targets. Response and movement times were recorded in parallel with
      electroencephalography (EEG). Behavioural analyses showed that participants with
      inconsistent hand preference were equally fast in initiating symmetrical and
      asymmetrical bimanual movements, whereas participants with consistent hand
      preference were slower in initiating (the more demanding) asymmetrical movements.
      Moreover, the amplitudes of the Movement Related Potential and the suppression of
      the 10 Hz-mu rhythm were larger in participants with inconsistent hand preference
      over premotor and primary sensorimotor areas, although it is possible that the
      suppression of the mu rhythm may also depend on hand dominance. Our findings
      suggest that individuals with inconsistent hand preference have an advantage in
      the planning and organization of bimanual movements, which may not be related to
      the direction of their hand dominance.

PMID- 24732381
TI  - Lack of automatic attentional orienting by gaze cues following a bilateral loss
      of visual cortex.
AB  - In social interactions, the location of relevant stimuli is often indicated by
      the orientation of gaze. It has been proposed that the direction of gaze might
      produce an automatic cueing of attention, similar to what is observed with
      exogenous cues. However, several reports have challenged this claim by
      demonstrating that the behavioral gain that arises with gaze cueing could be
      explained by shifts of attention, which are intentional and not automatic. We
      reasoned that if cueing by gaze was truly automatic, it should occur without
      awareness and should be sustained by subcortical circuits, including the
      amygdalae, independently of the main geniculo-striate visual pathway. We
      presented a cross-modal version of the Posner cueing paradigm to a patient (TN)
      with bilateral lesions of occipital cortex (Burra et al., 2013; Pegna, Khateb,
      Lazeyras, & Seghier, 2005). TN was asked to localize a sound using a key press.
      The location of the sound was congruent or incongruent with the direction of gaze
      of a face-cue. In groups of healthy young and age-matched participants, we
      observed significantly longer response times for incongruent than congruent
      sounds, suggesting that gaze direction interfered with processing of localized
      sounds. By contrast, TN's performance was not affected by sound-gaze congruence.
      The results suggest that the processing of gaze orientation cannot occur in the
      absence of geniculo-striate processing, suggesting that it is not automatic.

PMID- 24732380
TI  - Lin28 sustains early renal progenitors and induces Wilms tumor.
AB  - Wilms Tumor, the most common pediatric kidney cancer, evolves from the failure of
      terminal differentiation of the embryonic kidney. Here we show that
      overexpression of the heterochronic regulator Lin28 during kidney development in
      mice markedly expands nephrogenic progenitors by blocking their final wave of
      differentiation, ultimately resulting in a pathology highly reminiscent of Wilms
      tumor. Using lineage-specific promoters to target Lin28 to specific cell types,
      we observed Wilms tumor only when Lin28 is aberrantly expressed in multiple
      derivatives of the intermediate mesoderm, implicating the cell of origin as a
      multipotential renal progenitor. We show that withdrawal of Lin28 expression
      reverts tumorigenesis and markedly expands the numbers of glomerulus-like
      structures and that tumor formation is suppressed by enforced expression of Let-7
      microRNA. Finally, we demonstrate overexpression of the LIN28B paralog in a
      significant percentage of human Wilms tumor. Our data thus implicate the
      Lin28/Let-7 pathway in kidney development and tumorigenesis. 

PMID- 24732383
TI  - A cross-sectional developmental examination of the SNARC effect in a visually
      guided grasping task.
AB  - The present study documents the influence of numerical processing on hand and
      space use during a reach-to-grasp task. Three questions regarding the SNARC
      (spatial-numerical association of response codes) effect were asked: (1) would
      the SNARC effect influence hand and/or space preference for grasping?; (2) would
      the SNARC effect be demonstrated during the processing of one-digit numbers, two
      digit numbers, or both?; and (3) would developmental age influence the strength
      of the SNARC effect? A total of 84 participants in three age/school level groups
      (Primary, Secondary, and Post-secondary) took part in the study. Two identical
      sets of small wooden blocks numbered from 0 to 19 were used. Each set was
      presented to the right and to the left of each participant. A number was called
      and participants were asked to find and grasp a block with the corresponding
      number as fast and accurately as possible. Hand and space used (L/R) was recorded
      for each grasp. Number magnitude was shown to influence the selection of hand and
      hemi-space in accordance with the SNARC effect. In the small percentage of trials
      where the left hand was used, it was more commonly recruited to grasp blocks
      displaying low numbers than high numbers. Participants grasped blocks from left
      and right space with equal frequency, but respectively left/right space was
      accessed more often for blocks displaying low/high numbers. Regression analyses
      revealed that developmental age is a powerful predictor of the SNARC effect on
      hand and space selection for grasping. This study provides the first description
      of the SNARC effect on hand and space preference for the reach-to-grasp action.
      Results are discussed with relevant literature of numerical processing in the
      human brain.

PMID- 24732384
TI  - Novel insights into excipient effects on the biopharmaceutics of APIs from
      different BCS classes: Lactose in solid oral dosage forms.
AB  - Excipients encompass a wide range of properties that are of importance for the
      resulting drug product. Regulatory guidelines on biowaivers for immediate release
      formulations require an in depth understanding of the biopharmaceutic effects of
      excipients in order to establish bioequivalence between two different products
      carrying the same API based on dissolution tests alone. This paper describes a
      new approach in evaluating biopharmaceutic excipient effects. Actually used
      quantities of a model excipient, lactose, formulated in combination with APIs
      from different BCS classes were evaluated. The results suggest that companies use
      different (relative) amounts depending on the characteristics of the API. The
      probability of bioinequivalence due to a difference in lactose content between
      test and reference products was classified as low for BCS class I APIs and medium
      for BCS class II and III APIs, whereas a high probability was assigned to the
      combination of lactose and BCS class IV APIs. If repeated for other excipients,
      this retrospective, top-down approach may lead to a new database and more
      widespread applications of the biowaiver approach.

PMID- 24732386
TI  - Can technology help to reduce underage drinking? Evidence from the false ID laws
      with scanner provision.
AB  - Underage drinkers often use false identification to purchase alcohol or gain
      access into bars. In recent years, several states have introduced laws that
      provide incentives to retailers and bar owners who use electronic scanners to
      ensure that the customer is 21 years or older and uses a valid identification to
      purchase alcohol. This paper is the first to investigate the effects of these
      laws using confidential data from the National Longitudinal Survey of Youth, 1997
      Cohort (NLSY97). Using a difference-in-differences methodology, I find that the
      false ID laws with scanner provision significantly reduce underage drinking,
      including up to a 0.22 drink decrease in the average number of drinks consumed by
      underage youth per day. This effect is observed particularly in the short-run and
      more pronounced for non-college students and those who are relatively younger.
      These results are also robust under alternative model specifications. The
      findings of this paper highlight the importance of false ID laws in reducing
      alcohol consumption among underage youth. 

PMID- 24732387
TI  - The potentially protective effect of donepezil in Alzheimer's disease.
AB  - BACKGROUND/AIMS: Donepezil is an acetylcholinesterase inhibitor used to treat
      Alzheimer's disease (AD). In this study, we used a voxel-based specific regional
      analysis system for AD (VSRAD) to analyze the hippocampal volume and to assess
      the pharmacologic effects of donepezil as a disease modifier. METHODS: A total of
      185 AD patients underwent MRI, 120 (43 men and 77 women, 77.8 +/- 7.1 years)
      without and 65 (29 men and 36 women, 78.4 +/- 6.0 years) with donepezil
      treatment. VSRAD was compared in both groups and against a database of 80 normal
      subjects. The Z-score was used to assess the degree of hippocampal atrophy.
      RESULTS: No significant difference between the groups was found for age, sex, or
      Z-scores, but a significant difference was found for mean Mini-Mental State
      Examination (MMSE) scores (p = 0.02, Student's t test). Single regression
      analysis showed no significant association between Z-scores and MMSE scores in
      the treated group (p = 0.494), but a significant association in the untreated
      group (p = 0.001) was observed. This implies that the MMSE score becomes lower
      when the Z-score is higher in the untreated group, whereas there is no
      significant trend in the treated group. CONCLUSION: Donepezil affects the
      relationship between hippocampal volume and cognitive function and may therefore
      have a pharmacologic effect as a disease modifier.

PMID- 24732388
TI  - Gamma power and cognition in patients with schizophrenia and their first-degree
      relatives.
AB  - BACKGROUND: Gamma oscillations are essential for functional neural assembly
      formation underlying higher cerebral functions. Previous studies concerning gamma
      band power in schizophrenia have yielded diverse results. METHODS: In this study,
      we assessed gamma band power in minimally treated patients with schizophrenia,
      their first-degree relatives and healthy controls during an oddball paradigm
      performance, as well as the relation between gamma power and cognitive
      performance. RESULTS: We found a higher gamma power in the patient group than in
      the healthy controls at the P3, P4, Fz, Pz and T5 sites. Compared with their
      relatives, gamma power in the patients was only marginally higher over P3 and P4.
      We found a nearly significant inverse association between gamma power at F4 and
      Tower of London performance in the patients, as well as a significant inverse
      association between gamma power at T5 and verbal memory and working memory scores
      in the relatives. CONCLUSION: These results support higher total gamma power in
      association with schizophrenia and its inverse association with cognitive
      performance in patients and their first-degree relatives.

PMID- 24732389
TI  - Incidence of acute mastoiditis in Colorado children in the pneumococcal conjugate
      vaccine era.
AB  - BACKGROUND: Acute otitis media is among the most common reasons young children
      seek medical care, with Streptococcus pneumoniae the most common pathogen.
      Despite introduction of heptavalent pneumococcal conjugate vaccine (PCV7) in
      2000, recent experience suggests an increase in complications of acute otitis
      media, particularly acute mastoiditis. METHODS: We performed a retrospective
      review of acute mastoiditis in children from 1999 to 2008 using inpatient data
      from the Colorado Hospital Association and the Children's Hospital Colorado. The
      study included patients with documentation of acute mastoiditis or mastoidectomy
      and excluded those with chronic mastoiditis, chronic otitis media or
      cholesteatoma. RESULTS: The annual incidence of acute mastoiditis in children <2
      years/100,000 population was 11.0 in 2001 before decreasing to 4.6 in 2002 and
      4.5 in 2003. The incidence then increased to 12.0 in 2008 (total N = 242). The
      proportion of S. pneumoniae isolates nonsusceptible to penicillin increased from
      0% (0/16) between 1999 and 2004 to 38% (5/13) between 2005 and 2008 (P = 0.03).
      CONCLUSIONS: The incidence of acute mastoiditis in Colorado children <2 years of
      age exhibited a dynamic pattern from 1999 to 2008: a significant decline early
      after introduction of PCV7 that paralleled initial vaccine uptake, followed by an
      increase in subsequent years to pre-PCV7 levels. Replacement with non-PCV7
      pneumococcal serotypes and increased pneumococcal antibiotic resistance may be
      responsible for the increase in incidence to pre-PCV7 rates. Surveillance of
      mastoiditis incidence, pathogen distribution and resistance patterns following
      introduction of 13-valent PCV is warranted.

PMID- 24732390
TI  - Severe enterovirus type 71 nervous system infections in children in the Shanghai
      region of China: clinical manifestations and implications for prevention and
      care.
AB  - BACKGROUND: Severe outbreaks of enterovirus 71 (EV71) have been on the rise in
      the Western Pacific region, including in China since 2007. We describe features
      of pediatric patients admitted with severe disease EV71 to a tertiary care
      hospital during the 2010 ongoing outbreak in the Shanghai region. METHODS: The
      Shanghai EV71 outbreak was studied prospectively from January 2010 to December
      2012. To be eligible, children had to be 1 month to <14 years of age, admitted
      with confirmed EV71 infection to Xinhua Hospital and have severe illness needing
      Pediatric Infectious Diseases Service care with symptoms/signs of high prolonged
      fever and/or very unwell general appearance and/or neurological findings but no
      underlying medical condition. Clinical, laboratory, treatment discharge and
      follow-up data were recorded and analyzed. RESULTS: Of 26, 829 children
      presenting with possible EV71 disease, 2.9% (767) were admitted, more from less
      developed areas than from Shanghai proper. Of these, 29.2% (224) had severe
      enough EV71 for study enrolment, 4 excluded for underlying disease. Of 220
      enrolled, 40.5% (89) had neurological involvement, 10.5% (23) needed pediatric
      intensive care unit care and 3% (7) died. Factors associated with severe disease
      were young age, male gender, high white count, prolonged high fever, high
      glucose, high C-reactive protein and neurological findings. The majority with
      neurological involvement and all who died were from the countryside. Early
      intravenous gamma globulin intervention had better survival. No survivor had
      persistent sequelae 2 months after discharge. CONCLUSIONS: This study confirms
      the morbidity for EV71 disease in China, especially for patients from the
      countryside versus Shanghai proper. The potential impact of public education, an
      EV71 vaccine, and the potential benefits versus harms of IVIG treatment are
      discussed.

PMID- 24732391
TI  - Serotype 3 pneumococcal pleural empyema in an immunocompetent child after 13
      valent pneumococcal conjugate vaccine.

PMID- 24732392
TI  - Inhaled corticosteroids: not able to prevent post-bronchiolitis asthma.

PMID- 24732393
TI  - Recurrent deep pelvic muscle abscess.

PMID- 24732394
TI  - Staphylococcus aureus bacteremia without a localizing source in pediatric
      patients.
AB  - Staphylococcus aureus bacteremia without a localizing source in children is not
      well described. We identified patients with a positive blood culture for S.
      aureus from an 11-year surveillance study. Thirty-six cases of primary bacteremia
      were identified accounting for 5.7% of bacteremias. Most patients had
      comorbidities (86.1%), most commonly immunosuppression (33.3%). 

PMID- 24732395
TI  - Facile synthesis of soluble graphene quantum dots and its improved property in
      detecting heavy metal ions.
AB  - An effective approach to produce graphene quantum dots (GQDs) has been developed,
      which based on the cutting of graphene oxide (GO) powder into smaller pieces and
      being reduced by a green approach, using sodium polystyrene sulfonate (PSS) as a
      dispersant and l-ascorbic acid (l-AA) as the reducing agent, which is
      environmentally friendly. Then the as-prepared GQDs were further used for the
      detection of heavy metal ions Pb(2+). This kind of GQDs has greater solubility in
      water and is more biocompatible than GO that has been reduced by hydrazine
      hydrate. The few-layers of GQDs with defects and residual OH groups were shown to
      be particularly well suited for the determination of metal ions in the liquid
      phase using an electrochemical method, in which a remarkably low detection limit
      of 7*10(-9)M for Pb(2+) was achieved. 

PMID- 24732396
TI  - A novel hydrogen peroxide biosensor based on hemoglobin-collagen-CNTs composite
      nanofibers.
AB  - In this paper, carbon nanotubes (CNTs) were successfully incorporated in the
      composite composed of hemoglobin (Hb) and collagen using co-electrospinning
      technology. The formed Hb-collagen-CNTs composite nanofibers possessed distinct
      advantage of three-dimensional porous structure, biocompatibility and excellent
      stability. The Hb immobilized in the electrospun nanofibers retained its natural
      structure and the heterogeneous electron transfer rate constant (ks) of the
      direct electron transfer between Hb and electrodes was 5.3s(-1). In addition, the
      electrospun Hb-collagen-CNTs nanofibers modified electrodes showed good
      electrocatalytic properties toward H2O2 with a detection limit of 0.91MUM (signal
      to-noise ratio of 3) and the apparent Michaelis-Menten constant (Km(app)) of
      32.6MUM. 

PMID- 24732397
TI  - Bleomycin sulphate loaded nanostructured lipid particles augment oral
      bioavailability, cytotoxicity and apoptosis in cervical cancer cells.
AB  - In present investigation, bleomycin sulphate loaded nanostructured lipid
      particles (BLM-NLPs) were constructed to enhance the oral bioavailability by
      overwhelming the first pass hepatic metabolism. The particles size and
      nanoencapsulation efficiency of BLM-NLPs were measured to be 17.4+/-5.4nm and
      45.3+/-3.4%, respectively. Our studies indicated that the drug was molecularly
      dispersed in the lipid nanocoacervates, with amorphous geometry, without altering
      the chemical structure, as ascertained by spectral studies. The nanoformulation,
      BLM-NLPs was analyzed for dissolution testing, cytotoxicity, apoptosis and
      cellular uptake in human cervical cancer cell line, HeLa cells. BLM-NLPs released
      the drug with first order kinetic in simulated intestinal fluid (pH~6.8+/-0.1),
      characterized by initial burst and followed by slow release. Further, an enhanced
      cytotoxicity (~5.6 fold lower IC50), improved intracellular concentration (~4.38
      fold) and greater degree of apoptosis was induced by BLM-NLPs in HeLa cells, as
      compared to BLM alone. Moreover, BLM-NLPs also showed dose-dependent
      internalization, as evinced by cellular uptake study. The in vivo study indicated
      a significantly (P<0.0001) smaller elimination rate constant (KE), volume of
      distribution (Vd) and clearance rate (CLTotal) for BLM-NLPs, as compared to BLM
      solution in post-oral administrations. This clearly depicts the retention and
      stability of tailored nanoformulation in intestinal absorption pathway. In
      addition, our nanoformulation, BLM-NLPs documented significantly (P<0.0001)~3.4
      fold (66.20+/-2.57%) higher bioavailability than BLM solution (19.56+/-0.79%). In
      conclusion, our in vitro and in vivo results warrant the safety, efficacy and
      potency of tailored nanoformulation in clinical settings. 

PMID- 24732398
TI  - Modification of nanostructured calcium carbonate for efficient gene delivery.
AB  - In this study, a facile method to modify nanostructured calcium carbonate (CaCO3)
      gene delivery systems by adding calcium phosphate (CaP) component was developed.
      CaCO3/CaP/DNA nanoparticles were prepared by the co-precipitation of Ca(2+) ions
      with plasmid DNA in the presence of carbonate and phosphate ions. For comparison,
      CaCO3/DNA nanoparticles and CaP/DNA co-precipitates were also prepared. The
      effects of carbonate ion/phosphate ion (CO3(2-)/PO4(3-)) ratio on the particle
      size and gene delivery efficiency were investigated. With an appropriate CO3(2
      )/PO4(3-) ratio, the co-existence of carbonate and phosphate ions could control
      the size of co-precipitates effectively, and CaCO3/CaP/DNA nanoparticles with a
      decreased size and improved stability could be obtained. The in vitro gene
      transfections mediated by different nanoparticles in 293T cells and HeLa cells
      were carried out, using pGL3-Luc as a reporter plasmid. The gene transfection
      efficiency of CaCO3/CaP/DNA nanoparticles could be significantly improved as
      compared with CaCO3/DNA nanoparticles and CaP/DNA co-precipitates. The confocal
      microscopy study indicated that the cellular uptake and nuclear localization of
      CaCO3/CaP/DNA nanoparticles were significantly enhanced as compared with
      unmodified CaCO3/DNA nanoparticles. 

PMID- 24732400
TI  - Loss of collagen VII is associated with reduced transglutaminase 2 abundance and
      activity.
AB  - Absence of collagen VII leads to widespread cellular and tissue phenotypes.
      However, the underlying molecular mechanisms are not well understood. To gain
      insights into cellular responses to loss of collagen VII, we undertook a
      quantitative disease proteomics approach. By using recessive dystrophic
      epidermolysis bullosa (RDEB), a skin blistering disease caused by collagen VII
      deficiency, as a genetic model, collagen VII-dependent differences in cellular
      protein abundances and protein-protein interactions were analyzed. Absence of
      collagen VII led to alterations of intracellular protein compositions and to
      perturbations in cell adhesion, protein trafficking, and the turnover pathway
      autophagy. A potential linker of the different cellular phenotypes is
      transglutaminase 2 (TGM2), a multifunctional enzyme important for protein cross
      linking. TGM2 was identified as a stable interaction partner of collagen VII. In
      RDEB, both abundance and activity of TGM2 were reduced, accounting not only for
      diminished adhesion and perturbed autophagy but also for reduced cross-linking of
      the extracellular matrix and for decreased epidermal-dermal integrity in RDEB. 

PMID- 24732401
TI  - Human papillomavirus e7 oncoprotein transgenic skin develops an enhanced
      inflammatory response to 2,4-dinitrochlorobenzene by an arginase-1-dependent
      mechanism.
AB  - We have shown that the expression of human papillomavirus type 16 E7 (HPV16.E7)
      protein within epithelial cells results in local immune suppression and a weak
      and ineffective immune response to E7 similar to that occuring in HPV-associated
      premalignancy and cancers. However, a robust acute inflammatory stimulus can
      overcome this to enable immune elimination of HPV16.E7-transformed epithelial
      cells. 2,4-Dinitrochlorobenzene (DNCB) can elicit acute inflammation and it has
      been shown to initiate the regression of HPV-associated genital warts. Although
      the clinical use of DNCB is discouraged owing to its mutagenic potential,
      understanding how DNCB-induced acute inflammation alters local HPV16.E7-mediated
      immune suppression might lead to better treatments. Here, we show that topical
      DNCB application to skin expressing HPV16.E7 as a transgene induces a
      hyperinflammatory response, which is not seen in nontransgenic control animals.
      The E7-associated inflammatory response is characterized by enhanced expression
      of Th2 cytokines and increased infiltration of
      CD11b(+)Gr1(int)F4/80(+)Ly6C(hi)Ly6G(low) myeloid cells, producing arginase-1.
      Inhibition of arginase with an arginase-specific inhibitor, N(omega)-hydroxy-nor
      L-arginine, ameliorates the DNCB-induced inflammatory response. Our results
      demonstrate that HPV16.E7 protein enhances DNCB-associated production of arginase
      1 by myeloid cells and consequent inflammatory cellular infiltration of skin.

PMID- 24732402
TI  - Factors associated with nevus volatility in early adolescence.

PMID- 24732399
TI  - Basis for enhanced barrier function of pigmented skin.
AB  - Humans with darkly pigmented skin display superior permeability barrier function
      in comparison with humans with lightly pigmented skin. The reduced pH of the
      stratum corneum (SC) of darkly pigmented skin could account for enhanced
      function, because acidifying lightly pigmented human SC resets barrier function
      to darkly pigmented levels. In SKH1 (nonpigmented) versus SKH2/J (pigmented)
      hairless mice, we evaluated how a pigment-dependent reduction in pH could
      influence epidermal barrier function. Permeability barrier homeostasis is
      enhanced in SKH2/J versus SKH1 mice, correlating with a reduced pH in the lower
      SC that colocalizes with the extrusion of melanin granules. Darkly pigmented
      human epidermis also shows substantial melanin extrusion in the outer epidermis.
      Both acute barrier disruption and topical basic pH challenges accelerate
      reacidification of SKH2/J (but not SKH1) SC, while inducing melanin extrusion.
      SKH2/J mice also display enhanced expression of the SC acidifying enzyme,
      secretory phospholipase A2f (sPLA2f). Enhanced barrier function of SKH2/J mice
      could be attributed to enhanced activity of two acidic pH-dependent, ceramide
      generating enzymes, beta-glucocerebrosidase and acidic sphingomyelinase, leading
      to accelerated maturation of SC lamellar bilayers. Finally, organotypic cultures
      of darkly pigmented human keratinocytes display enhanced barrier function in
      comparison with lightly pigmented cultures. Together, these results suggest that
      the superior barrier function of pigmented epidermis can be largely attributed to
      the pH-lowering impact of melanin persistence/extrusion and enhanced sPLA2f
      expression. 

PMID- 24732403
TI  - Inhibitory effects of dietary Spirulina platensis on UVB-induced skin
      inflammatory responses and carcinogenesis.
AB  - Reactive oxygen species produced in response to UVR are important in skin tumor
      development. We have previously reported that deficiency of the Ogg1 gene,
      encoding the repair enzyme for 8-oxo-7,8-dihydroguanine (8-oxoG), increases skin
      tumor incidence in mice upon repetitive UVB exposure and modulation of UVB
      induced inflammatory response. Spirulina platensis is used as a human food
      supplement because it contains abundant nutritional and antioxidant components.
      Therefore, we investigated the inhibitory effects of S. platensis on UVB-induced
      skin tumor development in Ogg1 knockout-(KO) mice and the wild-type (WT)
      counterpart. Dietary S. platensis suppressed tumor induction and development in
      both genotypes compared with our previous data without S. platensis. Induction of
      erythema and ear swelling, one of the hallmarks of UVB-induced inflammatory
      responses, was suppressed in the skin of Ogg1-KO mice and albino hairless mice
      fed with dietary S. platensis. Compared with untreated mice, S. platensis
      administered mice showed significantly reduced 8-oxoG formation in the skin after
      UVB exposure. Moreover, we found that S. platensis effectively downregulated the
      signal proteins p38 mitogen-activated protein kinase, stress-activated protein
      kinase/c-Jun N-terminal kinase, and extracellular signal-regulated kinase after
      UVB exposure especially in Ogg1-KO mice. Our results suggest that S. platensis
      exerts antitumor effects against UVB irradiation in the skin through its anti
      inflammatory and antioxidant effects. 

PMID- 24732405
TI  - Practical treatment using mitotane for adrenocortical carcinoma.
AB  - PURPOSE OF REVIEW: Description of novel findings about the mechanism of action of
      mitotane and its activity as an adjunctive postoperative measure, or for
      treatment of advanced adrenocortical carcinoma. RECENT FINDINGS: Several in-vitro
      studies have shown that mitotane suppresses gene transcription of different
      enzymatic steps of the steroidogenetic pathway. Moreover, mitotane induces CYP3A4
      expression, thus accelerating the metabolic clearance of a variety of drugs
      including steroids. Retrospective studies provided evidence that adjunctive
      mitotane can prolong recurrence-free survival of treated patients. The concept of
      a therapeutic window of mitotane plasma concentrations was confirmed also for
      adjunctive treatment, but the relationship between mitotane concentration and
      given dose is loose. Genetic variability of the P450-dependent enzymes
      metabolizing mitotane may explain individual differences. SUMMARY: Mitotane
      concentration of 14-20  mg/l should be reached and maintained during treatment
      also in an adjunctive setting. In advanced adrenocortical carcinoma, a high-dose
      starting regimen should be employed when mitotane is used as monotherapy. The
      combination of mitotane with other drugs should consider the possibility of
      pharmacologic interactions due to mitotane-induced activation of drug metabolism.
      This concept applies also to steroid replacement in mitotane-treated patients,
      who need higher doses to adjust for increased steroid metabolism.

PMID- 24732404
TI  - Hygiene and other early childhood influences on the subsequent function of the
      immune system.
AB  - The immune system influences brain development and function. Hygiene and other
      early childhood influences impact the subsequent function of the immune system
      during adulthood, with consequences for vulnerability to neurodevelopmental and
      psychiatric disorders. Inflammatory events during pregnancy can act directly to
      cause developmental problems in the central nervous system (CNS) that have been
      implicated in schizophrenia and autism. The immune system also acts indirectly by
      "farming" the intestinal microbiota, which then influences brain development and
      function via the multiple pathways that constitute the gut-brain axis. The gut
      microbiota also regulates the immune system. Regulation of the immune system is
      crucial because inflammatory states in pregnancy need to be limited, and
      throughout life inflammation needs to be terminated completely when not required;
      for example, persistently raised levels of background inflammation during
      adulthood (in the presence or absence of a clinically apparent inflammatory
      stimulus) correlate with an increased risk of depression. A number of factors in
      the perinatal period, notably immigration from rural low-income to rich developed
      settings, caesarean delivery, breastfeeding and antibiotic abuse have profound
      effects on the microbiota and on immunoregulation during early life that persist
      into adulthood. Many aspects of the modern western environment deprive the infant
      of the immunoregulatory organisms with which humans co-evolved, while encouraging
      exposure to non-immunoregulatory organisms, associated with more recently evolved
      "crowd" infections. Finally, there are complex interactions between perinatal
      psychosocial stressors, the microbiota, and the immune system that have
      significant additional effects on both physical and psychiatric wellbeing in
      subsequent adulthood. This article is part of a Special Issue entitled
      Neuroimmunology in Health And Disease. 

PMID- 24732406
TI  - Evaluation of suicide cases in Turkey, 2007-2012.
AB  - BACKGROUND: The aim of this study was to determine the demographic and
      sociocultural characteristics of suicide attempts by using data from the Turkish
      Statistical Institute. It is our intent that the work data may contribute to the
      national suicide data and the development of suicide prevention policies.
      MATERIAL AND METHODS: We obtained our data, which cover the years 2007 to 2012,
      from the database accessible at the official website of the Turkish Statistical
      Institute, which permits the use of its data for research purposes. The data were
      evaluated by using the SPSS 10.0 program. The chi-square test was used for
      statistical analysis, and the percentage distribution and odds ratios were
      calculated. RESULTS: According to data from the Turkish Statistical Institute,
      the total number of suicide deaths in Turkey between 2007 and 2012 changed yearly
      (chi2=42,035-59,209; P<0.001). While suicide deaths in 2007 made up 0.00396% of
      the total deaths for that year, that figure increased to 0.00426% in 2013.
      According to the data from the Turkish Statistical Institute, over 1.9 million
      people died due to all causes between 2007 and 2012 in Turkey. Over 17,000 deaths
      (0.9%) were due to suicide. CONCLUSIONS: Suicide is an important public health
      problem and is multidimensional in nature. Examining this subject from
      etiological, epidemiological, biological, psychological, sociological, and
      anthropological perspectives is important to improve the prevention of suicides.

PMID- 24732407
TI  - Clarifying concepts of food parenting practices. A Delphi study with an
      application to snacking behavior.
AB  - Inconsistencies in measurements of food parenting practices continue to exist.
      Fundamental to this problem is the lack of clarity about what is understood by
      different concepts of food parenting practices. The purpose of this study was to
      clarify food parenting practice concepts related to snacking. A three round
      Delphi study among an international group of experts (n = 63) was conducted. In
      the first round, an open-ended survey was used to collect food parenting practice
      descriptions and concept labels associated with those practices. In the second
      round, participants were asked to match up descriptions with the appropriate
      concept labels. The third and final round allowed participants to reconsider how
      descriptions and concept labels were matched, taking into account the opinions
      expressed in round two. Round one produced 408 descriptions of food parenting
      practices and 110 different concept names. Round two started with 116
      descriptions of food parenting practices and 20 concept names. On 40
      descriptions, consensus regarding the underlying concept name was reached in
      round two. Of the remaining 76 descriptions, consensus on 47 descriptions
      regarding the underlying concept name was reached in round three. The present
      study supports the essential process of consensus development with respect to
      food parenting practices concepts.

PMID- 24732408
TI  - Impact of coexisting coronary artery disease on the occurrence of cerebral
      ischemic lesions after carotid stenting.
AB  - BACKGROUND: Coronary artery disease (CAD) may coexist with extracranial carotid
      artery stenosis (ECAS), but the influence of CAD on procedure-related
      complications after carotid artery stenting (CAS) has not been well investigated.
      The study aimed to determine the impact of CAD on the occurrence of peri-CAS
      cerebral ischemic lesions on diffusion-weighted imaging (DWI) scanning. METHODS:
      Coronary angiography was performed within six months before CAS. DWI scanning was
      repetitively done within 1 week before and after CAS. Clinical outcome measures
      were stroke, angina, myocardial infarction and death within 30 days. RESULTS:
      Among 126 patients (69.5+/-9.0 years) recruited for unilateral protected CAS, 33
      (26%) patients had peri-CAS DWI-positive lesions. CAD was noted in 79% (26 in 33)
      and 48% (45 in 93) of patients with and without peri-CAS DWI-positive lesions
      (OR, 4.0; 95% CI, 1.6-10.0; P = .0018), and the number of concomitant CAD on
      coronary angiography was positively correlated with the risk for peri-CAS DWI
      positive lesions (P = .0032). In patients with no CAD (n = 55), asymptomatic CAD
      (n = 41) and symptomatic CAD (n = 30), the occurrence rates of peri-CAS DWI
      positive lesions were 13%, 41% and 30% (P = .0048), and the peri-CAS stroke rates
      were 2%, 7% and 0% (P = .2120). CONCLUSIONS: The severity of morphological CAD
      and the presence of either symptomatic or asymptomatic CAD are associated with
      the occurrence of peri-CAS cerebral ischemic lesions.

PMID- 24732409
TI  - Plasminogen deficiency causes reduced corticospinal axonal plasticity and
      functional recovery after stroke in mice.
AB  - Tissue plasminogen activator (tPA) has been implicated in neurite outgrowth and
      neurological recovery post stroke. tPA converts the zymogen plasminogen (Plg)
      into plasmin. In this study, using plasminogen knockout (Plg-/-) mice and their
      Plg-native littermates (Plg+/+), we investigated the role of Plg in axonal
      remodeling and neurological recovery after stroke. Plg+/+ and Plg-/- mice (n =
      10/group) were subjected to permanent intraluminal monofilament middle cerebral
      artery occlusion (MCAo). A foot-fault test and a single pellet reaching test were
      performed prior to and on day 3 after stroke, and weekly thereafter to monitor
      functional deficit and recovery. Biotinylated dextran amine (BDA) was injected
      into the left motor cortex to anterogradely label the corticospinal tract (CST).
      Animals were euthanized 4 weeks after stroke. Neurite outgrowth was also measured
      in primary cultured cortical neurons harvested from Plg+/+ and Plg-/- embryos. In
      Plg+/+ mice, the motor functional deficiency after stroke progressively recovered
      with time. In contrast, recovery in Plg-/- mice was significantly impaired
      compared to Plg+/+ mice (p<0.01). BDA-positive axonal density of the CST
      originating from the contralesional cortex in the denervated side of the cervical
      gray matter was significantly reduced in Plg-/- mice compared with Plg+/+ mice
      (p<0.05). The behavioral outcome was highly correlated with the midline-crossing
      CST axonal density (R2>0.82, p<0.01). Plg-/- neurons exhibited significantly
      reduced neurite outgrowth. Our data suggest that plasminogen-dependent
      proteolysis has a beneficial effect during neurological recovery after stroke, at
      least in part, by promoting axonal remodeling in the denervated spinal cord. 

PMID- 24732410
TI  - High levels of Trypanosoma cruzi DNA determined by qPCR and infectiousness to
      Triatoma infestans support dogs and cats are major sources of parasites for
      domestic transmission.
AB  - The competence of reservoir hosts of vector-borne pathogens is directly linked to
      its capacity to infect the vector. Domestic dogs and cats are major domestic
      reservoir hosts of Trypanosoma cruzi, and exhibit a much higher infectiousness to
      triatomines than seropositive humans. We quantified the concentration of T. cruzi
      DNA in the peripheral blood of naturally-infected dogs and cats (a surrogate of
      intensity of parasitemia), and evaluated its association with infectiousness to
      the vector in a high-risk area of the Argentinean Chaco. To measure
      infectiousness, 44 infected dogs and 15 infected cats were each exposed to
      xenodiagnosis with 10-20 uninfected, laboratory-reared Triatoma infestans that
      blood-fed to repletion and were later individually examined for infection by
      optical microscopy. Parasite DNA concentration (expressed as equivalent amounts
      of parasite DNA per mL, Pe/mL) was estimated by real-time PCR amplification of
      the nuclear satellite DNA. Infectiousness increased steeply with parasite DNA
      concentration both in dogs and cats. Neither the median parasite load nor the
      mean infectiousness differed significantly between dogs (8.1Pe/mL and 48%) and
      cats (9.7Pe/mL and 44%), respectively. The infectiousness of dogs was positively
      and significantly associated with parasite load and an index of the host's body
      condition, but not with dog's age, parasite discrete typing unit and exposure to
      infected bugs in a random-effects multiple logistic regression model. Real-time
      PCR was more sensitive and less time-consuming than xenodiagnosis, and in
      conjunction with the body condition index, may be used to identify highly
      infectious hosts and implement novel control strategies. 

PMID- 24732412
TI  - Potential drug interactions with melatonin.
AB  - Possible interactions of melatonin with concurrently administered drugs were
      investigated in in vitro studies utilising human hepatic post-mitochondrial
      preparations; similar studies were conducted with rat preparations to ascertain
      whether rat is a suitable surrogate for human. Drugs were selected based not only
      on the knowledge that the 6-hydroxylation of exogenous melatonin, its principal
      pathway of metabolism, is mainly mediated by hepatic CYP1A2, but also on the
      likelihood of the drug being concurrently administered with melatonin. Hepatic
      preparations were incubated with either melatonin or 6-hydroxymelatonin in the
      presence and absence of a range of concentrations of interacting drug, and the
      production of 6-sulphatoxymelatonin monitored using a radioimmunoassay procedure.
      Of the drugs screened, only the potent CYP1A2 inhibitor 5-methoxypsoralen
      impaired the 6-melatonin hydroxylation at pharmacologically relevant
      concentrations, and is likely to lead to clinical interactions; diazepam,
      tamoxifen and acetaminophen (paracetamol) did not impair the metabolic conversion
      of melatonin to 6-sulphatoxymelatonin at concentrations attained following
      therapeutic administration. 17-Ethinhyloestradiol appeared not to suppress the 6
      hydroxylation of melatonin but inhibited the sulphation of 6-hydroxymelatonin,
      but this is unlikely to result in an interaction following therapeutic intake of
      the steroid. Species differences in the inhibition of melatonin metabolism in
      human and rat hepatic post-mitochondrial preparations were evident implying that
      the rat may not be an appropriate surrogate of human in such studies. 

PMID- 24732411
TI  - Novel mechanistic insights into treadmill exercise based rescue of social defeat
      induced anxiety-like behavior and memory impairment in rats.
AB  - Social defeat (SD) induced stress causes physiological and behavioral deficits in
      rodents, including depression and anxiety-like behaviors, as well as memory
      impairment. Anxiolytic and mood elevating effects of physical exercise are also
      known. However, rescue effect of physical exercise in social defeat-induced
      anxiety, depression or memory impairment has not been addressed. The role of
      epigenetic mechanisms that potentially contribute to these rescue or protective
      effects is also not known. The present study investigated the effect of moderate
      treadmill exercise on anxiety-like behavior and memory function in rats subjected
      to SD using a modified version of the resident-intruder model for social stress
      (defeat). Changes in histone acetylation and histone-modifying enzymes were
      examined in hippocampus, amygdala and frontal cortex which are considered
      critical for anxiety, depression and cognition. Sprague Dawley rats were randomly
      assigned in four groups; control, exercised, social defeat, social defeat and
      exercise. At the end of the SD or control exposure lasting 30 min daily for 7
      days, one group of SD rats was subjected to treadmill exercise for 2 weeks,
      whereas the other SD group was handled without exercise. Anxiety-like behavior
      tests and radial arm water maze test suggested that moderate treadmill exercise
      rescued social defeat induced anxiety-like behavior and memory impairment.
      Moreover, exercise normalized SD-induced increase in oxidative stress, most
      likely by adjusting antioxidant response. Our data suggests involvement of
      epigenetic mechanisms including histone acetylation of H3 and modulation of
      methyl-CpG-binding in the hippocampus that might contribute to the rescue effects
      of exercise in SD-induced behavioral deficits in rats.

PMID- 24732413
TI  - Social support modulates splenocyte glucocorticoid sensitivity in piglets exposed
      to social deprivation stress.
AB  - There is growing evidence that positive social interactions can attenuate the
      effects of stressful life experiences. However, little is known about the
      benefits of social partners on stress responses in farm animals. Therefore, in
      this study we examined the effects of social support on the endocrine and immune
      stress responses to a single 4h social deprivation in domestic piglets at 7, 21
      or 35days of age. The piglets were socially deprived of their mother and
      littermates. They were left alone (DA) or in the presence of a familiar (DF) or
      unfamiliar (DU) age-matched piglet. Non-socially deprived piglets served as a
      control. DA piglets displayed elevated plasma cortisol levels, higher
      lipopolysaccharide (LPS)-stimulated proliferation of splenocytes and increased
      TNF-alpha and IL-6 production in splenocyte cultures than the control piglets.
      There were no significant buffering effects of social partners on stress-induced
      plasma cortisol levels and splenocyte proliferation in response to LPS. However,
      the presence of an age-matched conspecific diminished the IL-6 production by
      splenocytes in younger, socially deprived piglets, and it reduced the TNF-alpha
      release in the older piglets. Compared to the controls, LPS-stimulated
      splenocytes from DA piglets were more resistant to the inhibitory effects of
      cortisol, which was demonstrated by a higher proliferative response and increased
      production of pro-inflammatory cytokines. The dose-dependent cortisol resistance
      was attenuated by the presence of a familiar or an unfamiliar conspecific at each
      of the three age categories. Indeed, in the present study, the familiarity level
      of the social partners did not seem to play a role in the alleviation of social
      stress-induced inflammatory activity and splenocyte cortisol resistance. In
      addition, the buffering effect of social support provided by an age-matched
      conspecific was more pronounced in older piglets. Conclusively, these findings
      suggest that social support is an important factor for enhancing piglets'
      abilities to cope with stressful challenges, and it may be a key approach needed
      to improve the health and welfare of farm animals. 

PMID- 24732414
TI  - The effects of caffeine ingestion on the reaction time and short-term maximal
      performance after 36 h of sleep deprivation.
AB  - The aim of the present study was to investigate the effects of caffeine ingestion
      on cognitive and physical performances after 36h of sleep deprivation. In
      randomized order, thirteen healthy male physical education students (age: 21.1+/
      1.1years, body mass: 77.1+/-7.2kg, height: 1.77+/-0.06m) completed four test
      sessions at 18:00h: after placebo or 5mg.kg(-1) of caffeine ingestion during a
      baseline night (RN) (bed time: from 22:30h to 07:00h) or a night of 36h of sleep
      deprivation (TSD). During each test session, participants performed the squat
      jump (SJ), the reaction time, and the 30-s Wingate tests (i.e., for the
      measurement of the peak (PP) and mean (MP) powers and the fatigue index (FI)).
      The results showed that PP and MP decreased and FI increased during the TSD
      compared to RN in the placebo condition (p<0.001). The caffeine ingestion
      improved PP after TSD compared to RN (p<0.001). SJ decreased significantly after
      the TSD compared to RN after both placebo and caffeine ingestions (p<0.001).
      However, SJ increased significantly after caffeine ingestion during RN and TSD
      (p<0.001). The reaction time increased significantly after TSD compared to RN
      (p<0.001). However, the reaction time decreased significantly after the caffeine
      ingestion only during the TSD (p<0.001). Therefore, caffeine is an effective
      strategy to counteract the effect of 36h of sleep loss on physical and cognitive
      performances. 

PMID- 24732415
TI  - Stress and reward: long term cortisol exposure predicts the strength of sexual
      preference.
AB  - Healthy individuals tend to consume available rewards like food and sex. This
      tendency is attenuated or amplified in most stress-related psychiatric
      conditions, so we asked if it depends on endogenous levels of the 'canonical
      stress hormone' cortisol. We unobtrusively quantified how hard healthy
      heterosexual men would work to consume erotic images of women versus men and also
      measured their exposure to endogenous cortisol in the prior two months. We used
      linear models to predict the strength of sexual preference from cortisol level,
      after accounting for other potential explanations. Heterosexual preference
      declines with self-reported anhedonia but increases with long term exposure to
      endogenous cortisol. These results suggest that cortisol may affect reward
      related behavior in healthy adults. 

PMID- 24732417
TI  - Endoplasmic reticulum stress is involved in restraint stress-induced hippocampal
      apoptosis and cognitive impairments in rats.
AB  - Long-term exposure to stressful stimuli can reduce hippocampal volume and cause
      cognitive impairments, but the underlying mechanisms are not well understood.
      Endoplasmic reticulum stress (ERS) is considered an early or initial response of
      cells under stress and linked to neuronal death in various neurodegenerative
      diseases. The present study investigated the involvement of ERS in restraint
      stress (RS)-induced hippocampal apoptosis and cognitive impairments. Using the
      rat RS model for 21 consecutive days, we found that the hippocampal apoptotic
      rate was significantly up-regulated as compared with unstressed controls, and
      salubrinal (ERS inhibitor) pretreatment effectively reduced the increase. As the
      marker of ERS, the 78-kDa glucose-regulated protein (GRP78) and the target
      molecule of the unfolded protein response (UPR), the splice variant of X-box
      binding protein 1 (sXBP-1) were also markedly increased in RS rats. Furthermore,
      in the three possible signaling pathways of ERS-induced apoptosis, the protein
      and mRNA levels of C/EBP homologous protein (CHOP) were significantly up
      regulated, and caspase-12 was activated and cleaved, which suggested that these
      two pathways crucially contributed to hippocampal cell death. However, we found
      no changes in protein levels of phosphorylated JNK, implying that the JNK pathway
      was not the primary pathway involved in hippocampal apoptosis. It is more
      important that the cognitive impairments caused by RS were also effectively
      alleviated by salubrinal pretreatment. The present results suggested that ERS in
      hippocampus was excessively activated under stress, and amelioration of ERS could
      be a novel strategy to prevent and treat impaired cognitive function induced by
      RS. 

PMID- 24732416
TI  - The neural signature of satiation is associated with ghrelin response and
      triglyceride metabolism.
AB  - Eating behavior is guided by a complex interaction between signals conveying
      information about energy stores, food availability, and palatability. How
      peripheral signals regulate brain circuits that guide feeding during sensation
      and consumption of a palatable food is poorly understood. We used fMRI to measure
      brain response to a palatable food (milkshake) when n=32 participants were fasted
      and fed with either a fixed-portion or ad libitum meal. We found that larger post
      prandial reductions in ghrelin and increases in triglycerides were associated
      with greater attenuation of response to the milkshake in brain regions regulating
      reward and feeding including the midbrain, amygdala, pallidum, hippocampus,
      insula and medial orbitofrontal cortex. Satiation-induced brain responses to
      milkshake were not related to acute changes in circulating insulin, glucose, or
      free fatty acids. The impact of a meal on the response to milkshake in the
      midbrain and dorsolateral prefrontal cortex differed depending upon whether meal
      termination was fixed or volitional, irrespective of the amount of food consumed.
      We conclude that satiation-induced changes in brain response to a palatable food
      are strongly and specifically associated with changes in circulating ghrelin and
      triglycerides and by volitional meal termination. 

PMID- 24732418
TI  - Effects of reversible deactivation of mossy fibers in the dentate-CA3 system on
      geometric center detection task in mice: Functional separation of spatial
      learning and its generalization to new environment.
AB  - Using diethyldithiocarbamate (DEDTC), a zinc chelator, we deactivated the mossy
      fibers that project from the dentate gyrus (DG) to the CA3 during acquisition and
      testing of a center detection task in mice. The mice were trained to find a food
      pellet at the center of four objects in a circular area. DEDTC injection just
      before the training sessions impaired this learning, whereas DEDTC injection
      before the probe test did not impair recall of the memory. DEDTC injection before
      a pattern completion test in which only one of the four objects was presented did
      not cause deficits in this test. DEDTC injection did, however, cause severe
      deficits in an array shift test in which all four objects were moved to new
      positions. These results demonstrated that 1) the DG-CA3 system plays a crucial
      role in the learning of geometric center detection task but not in its recall or
      pattern completion, and 2) the DG-CA3 system is involved in generalization to a
      new environment but is not crucial for pattern completion. 

PMID- 24732419
TI  - Effects of juvenile exposure to predator odor on adolescent and adult anxiety and
      pain nociception.
AB  - Clinical researchers have tracked patients with early life trauma and noted
      generalized anxiety disorder, unipolar depression, and risk-taking behaviors
      developing in late adolescence and into early adulthood. Animal models provide an
      opportunity to investigate the neural and developmental processes that underlie
      the relationship between early stress and later abnormal behavior. The present
      model used repeated exposure to 2,3,5-trimethyl-3-thiazoline (TMT), a component
      of fox feces, as an unconditioned fear-eliciting stimulus in order to induce
      stress in juvenile rats aged postnatal day (PND) 23 through 27. After further
      physical maturation characteristic of the adolescent stage (PND 42), animals were
      tested using an elevated plus maze (EPM) for anxiety and plantar test (Hargreaves
      method) for pain to assess any lingering effects of the juvenile stress. To
      assess how an additional stress later in life affects anxiety and pain
      nociception, PND 43 rats were exposed to inescapable shock (0.8mA) and again
      tested on EPM and plantar test. A final testing period was conducted in the adult
      (PND 63) rats to assess resulting changes in adult behaviors. TMT-exposed rats
      were significantly more anxious in adolescence than controls, but this difference
      disappeared after exposure to the secondary stressor. In adulthood, but not in
      adolescence, TMT-exposed rats demonstrated lower pain sensitivity than controls.
      These results suggest that early life stress can play a significant role in later
      anxiety and pain nociception, and offer insight into the development and
      manifestation of anxiety- and trauma-related disorders. 

PMID- 24732421
TI  - Brain microvascular endothelial cells resist elongation due to curvature and
      shear stress.
AB  - The highly specialized endothelial cells in brain capillaries are a key component
      of the blood-brain barrier, forming a network of tight junctions that almost
      completely block paracellular transport. In contrast to vascular endothelial
      cells in other organs, we show that brain microvascular endothelial cells resist
      elongation in response to curvature and shear stress. Since the tight junction
      network is defined by endothelial cell morphology, these results suggest that
      there may be an evolutionary advantage to resisting elongation by minimizing the
      total length of cell-cell junctions per unit length of vessel. 

PMID- 24732420
TI  - Ubiquitin carboxyl terminal hydrolyase L1-suppressed autophagic degradation of
      p21WAF1/Cip1 as a novel feedback mechanism in the control of cardiac fibroblast
      proliferation.
AB  - AIMS: Deubiquitinating enzymes (DUBs) appear to be critical regulators of a
      multitude of processes such as proliferation, apoptosis, differentiation, and
      inflammation; however, the potential roles of DUBs in the heart remain to be
      determined. This study was aimed to explore the role of a DUB, ubiquitin carboxyl
      terminal hydrolyase L1 (UCH-L1) in maladaptive cardiac remodeling and
      dysfunction. METHODS AND RESULTS: Maladaptive cardiac remodeling and dysfunction
      were induced in mice by transverse aortic constriction (TAC). UCH-L1 expression
      was transiently increased and then declined near to the basal level while
      impairment of cardiac function proceeded. The upregulation of UCH-L1 was observed
      in cardiac myocytes and fibroblasts. In primary culture of cardiac fibroblasts,
      UCH-L1 was upregulated by platelet-derived growth factor (PDGF)-BB and PDGF-DD.
      Adenoviral overexpession of UCH-L1 inhibited the PDGF-induced cardiac fibroblast
      proliferation without affecting the activation of mitogen activated protein
      kinases (MAPKs), Akt, and signal transducers and activators of transcription 3
      (STAT3). Further signaling dissection revealed that PDGF-BB posttranscriptional
      upregulated p21WAF1/Cip1 protein expression, which was inhibited by rapamycin, an
      activator of autophagy via suppressing mammalian target of rapamycin (mTOR),
      rather than MG132, a proteasome inhibitor. Overexpression of UCH-L1 enhanced PDGF
      BB-induced mTOR phosphorylation and upregulation of p21WAF1/Cip1 protein
      expression while suppressed autophagic flux in cardiac fibroblasts. CONCLUSION:
      UCH-L1 facilitates PDGF-BB-induced suppression of autophagic degradation of
      p21WAF1/Cip1 proteins in cardiac fibroblasts, which may serve as a novel negative
      feedback mechanism in the control of cardiac fibroblast proliferation
      contributing to cardiac fibrosis and dysfunction.

PMID- 24732422
TI  - An unexpected cause of diffuse alveolar hemorrhage in a kidney transplant
      patient.
AB  - Diffuse alveolar hemorrhage (DAH) is a life-threatening condition requiring
      urgent treatment. There are many different treatment-relevant causes of DAH,
      making the diagnostic approach to these patients complex and necessitating a
      multidisciplinary team. We report the case of a kidney transplant recipient in
      whom all diagnostic efforts did not reveal the cause of DAH, and only autopsy was
      able to establish an unexpected diagnosis.

PMID- 24732423
TI  - A math primer for engineers.

PMID- 24732424
TI  - Preface. Mathematics which are, or could be, useful in engineering, especially
      bioengineering.

PMID- 24732425
TI  - Thyroid status and cognitive function in euthyroid patients with early
      Parkinson's disease.
AB  - BACKGROUND: Alterations in thyroid hormone (TH) levels may be related to the
      pathogenesis of mild cognitive impairment (MCI) and dementia. Cognitive deficits
      are common in Parkinson's disease (PD) patients. The aim of this study was to
      investigate whether variations within the normal ranges of thyroid function are
      related to cognitive function in early PD without dementia. METHODS: Eighty-four
      euthyroid patients with early PD underwent evaluation of their thyroid status,
      including measures of thyroid-stimulating hormone (TSH), total triiodothyronine
      (tT3) and free thyroxine (fT4), and comprehensive neuropsychological tests.
      RESULTS: The 46 patients of the PD-MCI group did not differ in the serum levels
      of TH compared to the 38 patients of the PD-normal cognition group. fT4 levels
      were inversely associated with the Mini-Mental State Examination (MMSE) score and
      neuropsychological tests of attention and visuospatial and executive function.
      TSH and tT3 levels were not related to cognitive performances. After controlling
      for demographic and clinical variables, multiple regression analyses indicated
      statistically significant associations between fT4 concentrations and MMSE score
      and neuropsychological tests of executive function. CONCLUSIONS: This study
      supports a relationship between the thyroid status and cognitive function in
      euthyroid early PD patients, with higher concentrations of fT4 being associated
      with a poor performance of executive function.

PMID- 24732427
TI  - Role of mitochondrial electron transport chain dysfunction in Cr(VI)-induced
      cytotoxicity in L-02 hepatocytes.
AB  - BACKGROUND: Hexavalent chromium [Cr(VI)] and its compounds (e.g. chromates),
      which are extensively used in numerous industrial processes including leather
      tanning and steel manufacturing, are considered as priority pollutants. There is
      growing evidence supporting that Cr(VI) could be a human carcinogen that induces
      primary liver cancer after oral exposure, and this sheds light on the importance
      of the investigation of Cr(VI)-induced hepatotoxicity. Although it is known that
      mitochondria are major targets for heavy metals, the mechanisms of electron
      transfer chain (ETC) dysfunction involved in Cr(VI)-induced cytotoxicity are
      unclear. METHODS: In the present study, by using mitochondrial respiratory chain
      complex (MRCC) I inhibitor rotenone (ROT) and its substrates glutamate/malate
      (Glu/Mal), MRCC III inhibitor antimycin A (AA) and its substrate coenzyme Q
      (CoQ), and the antioxidant Vitamin C (Vit C), we aimed to elucidate the role of
      mitochondrial ETC dysfunction in Cr(VI)-induced cytotoxicity. RESULTS: We found
      that Cr(VI) targeted and inhibited MRCC I and III to induce ETC dysfunction,
      which played an important role in Cr(VI)-induced cytotoxicity. CONCLUSION: Our
      current data provides novel important insight into the mechanisms of
      mitochondrial ETC dysfunction in Cr(VI)-induced cytotoxicity in the hepatocytes,
      and we will be poised to develop new methods in the prevention and treatment of
      liver diseases involving mitochondrial ETC dysfunction for the occupational
      exposure population.

PMID- 24732428
TI  - Evolution of proliferation and the angiogenic switch in tumors with high clonal
      diversity.
AB  - Natural selection among tumor cell clones is thought to produce hallmark
      properties of malignancy. Efforts to understand evolution of one such hallmark-
      the angiogenic switch--has suggested that selection for angiogenesis can "run
      away" and generate a hypertumor, a form of evolutionary suicide by extreme
      vascular hypo- or hyperplasia. This phenomenon is predicted by models of tumor
      angiogenesis studied with the techniques of adaptive dynamics. These techniques
      also predict that selection drives tumor proliferative potential towards an
      evolutionarily stable strategy (ESS) that is also convergence-stable. However,
      adaptive dynamics are predicated on two key assumptions: (i) no more than two
      distinct clones or evolutionary strategies can exist in the tumor at any given
      time; and (ii) mutations cause small phenotypic changes. Here we show, using a
      stochastic simulation, that relaxation of these assumptions has no effect on the
      predictions of adaptive dynamics in this case. In particular, selection drives
      proliferative potential towards, and angiogenic potential away from, their
      respective ESSs. However, these simulations also show that tumor behavior is
      highly contingent on mutational history, particularly for angiogenesis.
      Individual tumors frequently grow to lethal size before the evolutionary endpoint
      is approached. In fact, most tumor dynamics are predicted to be in the
      evolutionarily transient regime throughout their natural history, so that
      clinically, the ESS is often largely irrelevant. In addition, we show that clonal
      diversity as measured by the Shannon Information Index correlates with the speed
      of approach to the evolutionary endpoint. This observation dovetails with results
      showing that clonal diversity in Barrett's esophagus predicts progression to
      malignancy.

PMID- 24732429
TI  - Bioimage Informatics in the context of Drosophila research.
AB  - Modern biological research relies heavily on microscopic imaging. The advanced
      genetic toolkit of Drosophila makes it possible to label molecular and cellular
      components with unprecedented level of specificity necessitating the application
      of the most sophisticated imaging technologies. Imaging in Drosophila spans all
      scales from single molecules to the entire populations of adult organisms, from
      electron microscopy to live imaging of developmental processes. As the imaging
      approaches become more complex and ambitious, there is an increasing need for
      quantitative, computer-mediated image processing and analysis to make sense of
      the imagery. Bioimage Informatics is an emerging research field that covers all
      aspects of biological image analysis from data handling, through processing, to
      quantitative measurements, analysis and data presentation. Some of the most
      advanced, large scale projects, combining cutting edge imaging with complex
      bioimage informatics pipelines, are realized in the Drosophila research
      community. In this review, we discuss the current research in biological image
      analysis specifically relevant to the type of systems level image datasets that
      are uniquely available for the Drosophila model system. We focus on how state-of
      the-art computer vision algorithms are impacting the ability of Drosophila
      researchers to analyze biological systems in space and time. We pay particular
      attention to how these algorithmic advances from computer science are made usable
      to practicing biologists through open source platforms and how biologists can
      themselves participate in their further development. 

PMID- 24732430
TI  - Excitability and responsiveness of rat barrel cortex neurons in the presence and
      absence of spontaneous synaptic activity in vivo.
AB  - The amplitude and temporal dynamics of spontaneous synaptic activity in the
      cerebral cortex vary as a function of brain states. To directly assess the impact
      of different ongoing synaptic activities on neocortical function, we performed in
      vivo intracellular recordings from barrel cortex neurons in rats under two
      pharmacological conditions generating either oscillatory or tonic synaptic drive.
      Cortical neurons membrane excitability and firing responses were compared, in the
      same neurons, before and after complete suppression of background synaptic drive
      following systemic injection of a high dose of anaesthetic. Compared to the
      oscillatory state, the tonic pattern resulted in a more depolarized and less
      fluctuating membrane potential (Vm), a lower input resistance (Rm) and steeper
      relations of firing frequency versus injected current (F-I). Whatever their
      temporal dynamics, suppression of background synaptic activities increased mean
      Vm, without affecting Rm, and induced a rightward shift of F-I curves. Both types
      of synaptic drive generated a high variability in current-induced firing rate and
      patterns in cortical neurons, which was much reduced after removal of spontaneous
      activity. These findings suggest that oscillatory and tonic synaptic patterns
      differentially facilitate the input-output function of cortical neurons but
      result in a similar moment-to-moment variability in spike responses to incoming
      depolarizing inputs. 

PMID- 24732431
TI  - Prognostic value of metastatic nodal volume and lymph node ratio in patients with
      cervical lymph node metastases from an unknown primary tumor.
AB  - OBJECTIVE: The presence of metastatic cervical lymph nodes (MCNs) is an
      unfavorable prognostic factor in head and neck cancer. The total volume of MCNs
      (MNV) and the lymph node ratio (LNR) may be superior to conventional nodal
      staging in cervical metastasis from an unknown primary tumor (CUP). We evaluated
      the prognostic value of MNV and LNR in CUP patients. METHODS: Thirty-nine
      patients with CUP who underwent surgery plus postoperative radiotherapy were
      reviewed. MNV was measured by preoperative computed tomography and LNR was
      determined using neck dissection samples. The association of clinicopathologic
      factors, MNV, and LNR with disease-free survival (DFS) and overall survival (OS)
      was analyzed. RESULTS: Five-year DFS and OS were 68.4 and 70.8%, respectively,
      for a median follow-up of 49 months. In multivariate analysis, MNV (>30 ml) was
      an independent prognostic factor for both DFS and OS (p = 0.004 and p < 0.001,
      respectively). LNR (>0.14) was identified as an independent predictive factor for
      DFS (p = 0.041). CONCLUSION: MNV and LNR are independent prognostic factors in
      patients with CUP and could facilitate the identification of high-risk patients
      requiring intensive treatment and surveillance.

PMID- 24732432
TI  - Effectiveness of subcutaneous versus sublingual immunotherapy for allergic
      rhinitis: current update.
AB  - PURPOSE OF REVIEW: The effectiveness of subcutaneous immunotherapy (SCIT) and
      sublingual immunotherapy (SLIT) in treatment of patients suffering from allergic
      rhinitis have been evaluated in a number of randomized controlled trials,
      systematic reviews and meta-analyses conducted over the past few decades.
      Currently, there is a growing interest in evaluating comparative effectiveness of
      SCIT versus SLIT to identify whether one form of immunotherapy is better than the
      other. In this current update, we discuss pertinent systematic reviews that have
      addressed this concern. RECENT FINDINGS: The four systematic reviews identified
      in this update are the only reviews of effectiveness of SCIT versus SLIT for
      allergic rhinitis available in the literature. Through direct and indirect
      comparisons, these four reviews demonstrate that SCIT is better than SLIT in
      reducing symptoms of allergic rhinitis and rescue medication use in adults and
      children. However, there was no difference between the two forms of immunotherapy
      in reducing combined symptom-medication scores and improving quality of life.
      With regard to safety, SLIT had fewer systemic reactions when compared with SCIT.
      SUMMARY: The evidence of effectiveness of SCIT versus SLIT was principally
      derived from indirect comparisons and meta-regression. Additional randomized
      controlled trials of head-to-head comparisons of SCIT versus SLIT are required to
      strengthen this evidence base. Future research should focus on development of
      standardized outcome assessment, allergen dosing, content, and treatment regimes.

PMID- 24732434
TI  - Barriers to uniformity within the endoplasmic reticulum.
AB  - Differentiating the endoplasmic reticulum (ER) into different physical domains
      may help the ER spatially regulate its many functions. For example, ER sheets are
      highly decorated with ribosomes for protein synthesis, whereas tubules usually
      correspond to smooth ER. Hence, ER morphology may play direct roles in functional
      diversification within the ER. The ER also makes direct physical contacts with
      other organelles, called ER junctions, enabling further functional
      diversification through input from external sources. In yeast, an ER diffusion
      barrier has now been discovered at the bud neck that compartmentalizes the ER
      into bud and mother diffusion domains by restricting the lateral diffusion of ER
      membrane proteins. Therefore, diffusion barriers also likely contribute to
      functional diversification within the ER by creating suites of molecular factors
      within ER diffusion domains. 

PMID- 24732433
TI  - Mechanistic elucidation of the antitumor properties of withaferin a in breast
      cancer.
AB  - Withaferin A (WFA) is a steroidal lactone with antitumor effects manifested at
      multiple levels that are mechanistically obscure. Using a phospho-kinase
      screening array, we discovered that WFA activated phosphorylation of the S6
      kinase RSK (ribosomal S6 kinase) in breast cancer cells. Pursuing this
      observation, we defined activation of extracellular signal-regulated kinase (ERK)
      RSK and ETS-like transcription factor 1 (Elk1)-CHOP (C-EBP homologous protein)
      kinase pathways in upregulating transcription of the death receptor 5 (DR5).
      Through this route, WFA acted as an effective DR5 activator capable of
      potentiating the biologic effects of celecoxib, etoposide, and TRAIL.
      Accordingly, WFA treatment inhibited breast tumor formation in xenograft and
      mouse mammary tumor virus (MMTV)-neu mouse models in a manner associated with
      activation of the ERK/RSK axis, DR5 upregulation, and elevated nuclear
      accumulation of Elk1 and CHOP. Together, our results offer mechanistic insight
      into how WFA inhibits breast tumor growth.

PMID- 24732435
TI  - Non-DSB clustered DNA lesions induced by ionizing radiation are largely
      responsible for the loss of plasmid DNA functionality in the presence of
      cisplatin.
AB  - The combination of cisplatin and ionizing radiation (IR) increases cell toxicity
      by both enhancing DNA damage and inhibiting repair mechanisms. Although the
      formation of cluster DNA lesions, particularly double-strand breaks (DSB) at the
      site of cisplatin-DNA-adducts has been reported to induce cell death, the
      contribution of DSB and non-DSB cluster lesions to the cellular toxicity is still
      unknown. Although both lesions are toxic, it is not always possible to measure
      their frequency and cell survival in the same model system. To overcome this
      problem, here, we investigate the effect of cisplatin-adducts on the induction of
      DSB and non-DSB cluster DNA lesions by IR and determine the impact of such
      lesions on plasmid functionality. Cluster lesions are two or more lesions on
      opposite DNA strands with a short distance such that error free repair is
      difficult or impossible. At a ratio of two cisplatin per plasmid, irradiation of
      platinated DNA in solution with (137)Cs gamma-rays shows enhancements in the
      formation of DNA DSB and non-DSB cluster lesions by factors of 2.6 and 2.1,
      respectively, compared to unmodified DNA. However, in absolute terms, the yield
      for non-DSB cluster lesions is far larger than that for DSB, by a factor of 26.
      Unmodified and cisplatin-modified DNA were irradiated and subsequently
      transformed into Escherichia coli to give survival curves representing the
      functionality of the plasmid DNA as a function of radiation dose. Our results
      demonstrate that non-DSB cluster lesions are the only toxic lesions present at a
      sufficient frequency to account for the loss of DNA functionality. Our data also
      show that Frank-DSB lesions are simply too infrequent to account for the loss of
      DNA functionality. In conclusion, non-DSB cluster DNA damage is known to be
      difficult to repair and is probably the lesion responsible for the loss of
      functionality of DNA modified by cisplatin. 

PMID- 24732436
TI  - Mitochondrion role in molecular basis of cytoplasmic male sterility.
AB  - Cytoplasmic male sterility and its fertility restoration via nuclear genes offer
      the possibility to understand the role of mitochondria during microsporogenesis.
      In most cases rearrangements in the mitochondrial DNA involving known
      mitochondrial genes as well as unknown sequences result in the creation of new
      chimeric open reading frames, which encode proteins containing transmembrane
      domains. So far, most of the CMS systems have been characterized via restriction
      fragment polymorphisms followed by transcript analysis. However, whole
      mitochondrial genome sequence analyses comparing male sterile and fertile
      cytoplasm open options for deeper insights into mitochondrial genome
      rearrangements. We more and more start to unravel how mitochondria are involved
      in triggering death of the male reproductive organs. Reduced levels of ATP
      accompanied by increased concentrations of reactive oxygen species, which are
      produced more under conditions of mitochondrial dysfunction, seem to play a major
      role in the fate of pollen production. Nuclear genes, so called restorer-of
      fertility are able to restore the male fertility. Fertility restoration can occur
      via pentatricopeptide repeat (PPR) proteins or via different mechanisms involving
      non-PPR proteins. 

PMID- 24732437
TI  - RNA editing in plant mitochondria-connecting RNA target sequences and acting
      proteins.
AB  - RNA editing changes several hundred cytidines to uridines in the mRNAs of
      mitochondria in flowering plants. The target cytidines are identified by a
      subtype of PPR proteins characterized by tandem modules which each binds with a
      specific upstream nucleotide. Recent progress in correlating repeat structures
      with nucleotide identities allows to predict and identify target sites in
      mitochondrial RNAs. Additional proteins have been found to play a role in RNA
      editing; their precise function still needs to be elucidated. The enzymatic
      activity performing the C to U reaction may reside in the C-terminal DYW
      extensions of the PPR proteins; however, this still needs to be proven. Here we
      update recent progress in understanding RNA editing in flowering plant
      mitochondria. 

PMID- 24732439
TI  - The long and short of antiviral defense: small RNA-based immunity in insects.
AB  - The host RNA interference (RNAi) pathway of insects senses virus infection and
      induces an antiviral response to restrict virus replication. Dicer-2 detects
      viral double-stranded RNA, produced by RNA and DNA viruses, and generates viral
      small interfering RNAs (vsiRNAs). Recent small RNA profiling studies provided new
      insights into the viral RNA substrates that trigger vsiRNA biogenesis. The
      importance of the antiviral RNAi pathway is underscored by the observation that
      viruses have evolved sophisticated mechanisms to counteract this small RNA-based
      immune response. More recently, it was proposed that another small RNA silencing
      mechanism, the piRNA pathway, also processes viral RNAs in Drosophila and
      mosquitoes. Here, we review recent insights into the mechanism of antiviral RNAi,
      viral small RNA profiles, and viral counter-defense mechanisms in insects. 

PMID- 24732440
TI  - Flash electroretinogram and addictive disorders.

PMID- 24732438
TI  - Preventing non bacteremic pneumococcal pneumonia in older adults: historical
      background and considerations for choosing between PCV13 and PPV23.

PMID- 24732441
TI  - Short-term effects of electronic and tobacco cigarettes on exhaled nitric oxide.
AB  - The objective of this study was to compare the short-term respiratory effects due
      to the inhalation of electronic and conventional tobacco cigarette-generated
      mainstream aerosols through the measurement of the exhaled nitric oxide (eNO). To
      this purpose, twenty-five smokers were asked to smoke a conventional cigarette
      and to vape an electronic cigarette (with and without nicotine), and an
      electronic cigarette without liquid (control session). Electronic and tobacco
      cigarette mainstream aerosols were characterized in terms of total particle
      number concentrations and size distributions. On the basis of the measured total
      particle number concentrations and size distributions, the average particle doses
      deposited in alveolar and tracheobronchial regions of the lungs for a single 2-s
      puff were also estimated considering a subject performing resting (sitting)
      activity. Total particle number concentrations in the mainstream resulted equal
      to 3.5+/-0.4*10(9), 5.1+/-0.1*10(9), and 3.1+/-0.6*10(9) part. cm(-3) for
      electronic cigarettes without nicotine, with nicotine, and for conventional
      cigarettes, respectively. The corresponding alveolar doses for a resting subject
      were estimated equal to 3.8*10(10), 5.2*10(10) and 2.3*10(10) particles. The mean
      eNO variations measured after each smoking/vaping session were equal to 3.2ppb,
      2.7ppb and 2.8ppb for electronic cigarettes without nicotine, with nicotine, and
      for conventional cigarettes, respectively; whereas, negligible eNO changes were
      measured in the control session. Statistical tests performed on eNO data showed
      statistically significant differences between smoking/vaping sessions and the
      control session, thus confirming a similar effect on human airways whatever the
      cigarette smoked/vaped, the nicotine content, and the particle dose received. 

PMID- 24732442
TI  - DNA damage in internal organs after cutaneous exposure to sulphur mustard.
AB  - Sulphur mustard (SM) is a chemical warfare agent that attacks mainly skin, eye
      and lungs. Due to its lipophilic properties, SM is also able to diffuse through
      the skin and reach internal organs. DNA represents one of the most critical
      molecular targets of this powerful alkylating agent which modifies DNA structure
      by forming monoadducts and biadducts. These DNA lesions are involved in the acute
      toxicity of SM as well as its long-term carcinogenicity. In the present work we
      studied the formation and persistence of guanine and adenine monoadducts and
      guanine biadducts in the DNA of brain, lungs, kidneys, spleen, and liver of SKH-1
      mice cutaneously exposed to 2, 6 and 60mg/kg of SM. SM-DNA adducts were detected
      in all studied organs, except in liver at the two lowest doses. Brain and lungs
      were the organs with the highest level of SM-DNA adducts, followed by kidney,
      spleen and liver. Monitoring the level of adducts for three weeks after cutaneous
      exposure showed that the lifetime of adducts were not the same in all organs,
      lungs being the organ with the longest persistence. Diffusion from skin to
      internal organs was much more efficient at the highest compared to the lowest
      dose investigated as the result of the loss of the skin barrier function. These
      data provide novel information on the distribution of SM in tissues following
      cutaneous exposures and indicate that brain is an important target. 

PMID- 24732443
TI  - Persistent modification of Nav1.9 following chronic exposure to insecticides and
      pyridostigmine bromide.
AB  - Many veterans of the 1991 Gulf War (GW) returned from that conflict with a
      widespread chronic pain affecting deep tissues. Recently, we have shown that a
      60day exposure to the insecticides permethrin, chlorpyrifos, and pyridostigmine
      bromide (NTPB) had little influence on nociceptor action potential forming
      Nav1.8, but increased Kv7 mediated inhibitory currents 8weeks after treatment.
      Using the same exposure regimen, we used whole cell patch methods to examine
      whether the influences of NTPB could be observed on Nav1.9 expressed in muscle
      and vascular nociceptors. During a 60day exposure to NTPB, rats exhibited lowered
      muscle pain thresholds and increased rest periods, but these measures
      subsequently returned to normal levels. Eight and 12weeks after treatments
      ceased, DRG neurons were excised from the sensory ganglia. Whole cell patch
      studies revealed little change in voltage dependent activation and deactivation
      of Nav1.9, but significant increases in the amplitude of Nav1.9 were observed
      8weeks after exposure. Cellular studies, at the 8week delay, revealed that NTPB
      also significantly prolonged action potential duration and afterhyperpolarization
      (22 degrees C). Acute application of permethrin (10MUM) also increased the
      amplitude of Nav1.9 in skin, muscle and vascular nociceptors. In conclusion,
      chronic exposure to Gulf War agents produced long term changes in the amplitude
      of Nav1.9 expressed in muscle and vascular nociceptors. The reported increases in
      Kv7 amplitude may have been an adaptive response to increased Nav1.9, and
      effectively suppressed behavioral pain measures in the post treatment period.
      Factors that alter the balance between Nav1.9 and Kv7 could release spontaneous
      discharge and produce chronic deep tissue pain. 

PMID- 24732444
TI  - A new scale for the assessment of performance and capacity of hand function in
      children with hemiplegic cerebral palsy: reliability and validity studies.
AB  - BACKGROUND: In hemiplegic children, the recognition of the activity limitation
      pattern and the possibility of grading its severity are relevant for clinicians
      while planning interventions, monitoring results, predicting outcomes. OBJECTIVE:
      Aim of the study is to examine the reliability and validity of Besta Scale, an
      instrument used to measure in hemiplegic children from 18 months to 12 years of
      age both grasp on request (capacity) and spontaneous use of upper limb
      (performance) in bimanual play activities and in ADL. DESIGN: Psychometric
      analysis of reliability and of validity of the Besta scale was performed.
      SETTING: Outpatient study sample METHODS: Reliability study: A sample of 39
      patients was enrolled. The administration of Besta scale was video-recorded in a
      standardized manner. All videos were scored by 20 independent raters on
      subsequent viewing. 3 raters randomly selected from the 20-raters group rescored
      the same video two years later for intra-rater reliability. Intra and inter-rater
      reliability were calculated using Intraclass Correlation Coefficient (ICC) and
      Kendall's coefficient (K), respectively. Internal consistency reliability was
      assessed using Alpha's Chronbach coefficient. Validity study: a sample of 105
      children was assessed 5 times (at t0 and 2, 3, 6 and 12 months later) by 20
      independent raters. Each patient underwent at the same time to QUEST and Besta
      scale administration and assessment. Criterion validity was calculated using rho
      Pearson coefficient. RESULTS: Reliability study: The inter-rater reliability
      calculated with Kendall's coefficient resulted moderate K=0.47. The intra-rater
      (or test-retest) reliability for 3 raters was excellent (ICC=0.927). The
      Cronbach's alpha for internal consistency was 0.972. Validity study: Besta scale
      showed a good criterion validity compared to QUEST increasing by age and severity
      of impairment. Rho Pearson's correlation coefficient r was 0.81 (P<0.0001).
      Limitations. Besta scales in infants finds hard to distinguish between mild to
      moderately impaired hand function. CONCLUSIONS: Besta scale scoring system is a
      valid and reliable tool, utilizable in a clinical setting to monitor evolution of
      unimanual and bimanual manipulation and to distinguish hand's capacity from
      performance.

PMID- 24732445
TI  - Management and outcomes of pneumonia among children with complex chronic
      conditions.
AB  - INTRODUCTION: Although pneumonia is a common reason for pediatric hospitalization
      among children with complex chronic conditions (CCC), treatment and outcomes have
      not been well-described. We characterized the presentation, management and
      outcomes of pneumonia in children with and without CCC and described how
      antibiotic management and outcomes vary among subgroups of children with CCC.
      METHODS: We conducted a cohort study of children <18 years with pneumonia across
      a large sample of US hospitals. Children were grouped according to CCC subgroups.
      Differences in disease management and outcomes were assessed using multivariable
      regression. RESULTS: Of the 31,684 children in our cohort, 11.9% had CCC.
      Children with CCC were more likely to receive intensive investigations and
      therapies, were less likely to receive aminopenicillins or third generation
      cephalosporins and were more likely to receive antibiotics against methicillin
      resistant Staphylococcus aureus, Pseudomonas aeruginosa and anaerobes. Compared
      with children without these conditions, children with CCC had significantly
      increased length of stay [relative risk 1.43, 95% confidence interval (CI) 1.39
      1.48] and hospital costs (relative risk 1.38, 95% CI 1.33-1.43), with increased
      odds of antibiotic escalation (odds ratio 1.51, 95% CI 1.35-1.70), pneumonia
      complications (odds ratio 1.47, 95% CI 1.24-1.75) and readmission (odds ratio
      4.0, 95% CI 3.2-5.0). DISCUSSION: Children with CCC comprise a significant
      proportion of children hospitalized for pneumonia and are at substantially
      increased risk of adverse outcomes. They have high rates of treatment with broad
      spectrum antibiotics, both at the time of hospitalization and subsequently.
      Research is needed to inform decision-making and guideline development, with
      goals of reducing adverse outcomes and unnecessary variation in management among
      children with CCC.

PMID- 24732446
TI  - Acute myopericarditis associated with cat scratch disease in an adolescent.
AB  - Cat scratch disease is generally characterized by a self-limited chronic regional
      lymphadenopathy, but numerous other clinical manifestations involving a variety
      of organ systems have been reported. Cardiac involvement is unusual and when
      reported, it has been associated with culture-negative endocarditis in adults. We
      present the case of an adolescent male with typical cat scratch disease and
      associated myopericarditis. 

PMID- 24732447
TI  - Factors affecting time to death from start of treatment among children succumbing
      to bacterial meningitis.
AB  - BACKGROUND: Many risks of death in childhood bacterial meningitis are well
      identified, but factors influencing survival time have received less attention.
      Better understanding of this issue could help explain why adjuvant medications
      have performed unevenly in different trials. METHODS: In a post hoc analysis of
      prospectively collected data from a large bacterial meningitis treatment trial in
      Luanda, Angola, we compared time to death after initiation of antimicrobial
      treatment among 206 children with etiology and other patient characteristics. The
      risks of dying very quickly (0-4 hours), quickly (4-8 hours) or after longer
      periods were analyzed by logistic regression. RESULTS: Median time to death was
      18.5 hours, half the time in Streptococcus pneumoniae (11.8 hours) compared with
      Haemophilus influenzae (26.8 hours) meningitis. Of all deaths caused by
      pneumococcal or H.influenzae meningitis, 42% versus 16%, respectively, occurred
      within the first 8 hours. In addition, patients who succumbed within 8 hours,
      unlike those dying later, had a short disease history, shock, hypoglycemia and
      poor cerebrospinal fluid white cell response. CONCLUSIONS: Time to death in
      Angola is so short that hardly anything, except perhaps modern intensive care, is
      likely to improve outcome in a patient with meningitis, especially the
      pneumococcal disease.

PMID- 24732448
TI  - Melioidosis: a pediatric disease.

PMID- 24732449
TI  - Intussusception and rotavirus vaccines: consensus on benefits outweighing
      recognized risk.

PMID- 24732450
TI  - Skin-homing Th2/Th22 cells in papuloerythroderma of Ofuji.
AB  - Papuloerythroderma of Ofuji (PEO) appears to be a T cell-mediated skin disease;
      however, the pathogenesis of PEO remains unclear. We report two cases of PEO and
      examine cytokine production and expression of skin-homing receptors in
      circulating T cells in the patients. The percentages of interleukin 4 (IL-4)-, IL
      13- and IL-22-producing CD4+ and CD8+ T cells were markedly higher in the
      circulation of patients with PEO than in those of healthy subjects. The
      expression of both cutaneous lymphocyte antigen (CLA) and CC chemokine receptor 4
      (CCR4) were significantly upregulated in the circulating CD4+ and CD8+ T cells.
      Moreover, serum levels of thymus and activation-regulated chemokine (TARC), a
      chemoattractant for CCR4, were increased. The number of IL-4-, IL-13- and IL-22
      producing T cells, expression of CLA and CCR4 by T cells, and serum TARC levels
      significantly decreased after complete remission of PEO. These results suggest
      that skin-homing Th2/Th22 cells may play a role in the pathogenesis of PEO.

PMID- 24732451
TI  - Role of local bioactivation of vitamin D by CYP27A1 and CYP2R1 in the control of
      cell growth in normal endometrium and endometrial carcinoma.
AB  - Vitamin D (VD) deficiency has been suggested as a risk factor for cancer. One
      recognized mechanism is that the low-serum 25-hydroxyvitamin D (25(OH)D) of VD
      deficiency reduces intratumoral 25(OH)D conversion to 1alpha,25-dihydroxyvitamin
      D (1,25D, the hormonal form of VD), compromising 1,25D-VD receptor (VDR)
      antitumoral actions. Reduced tumoral VDR and increased CYP24A1, the enzyme that
      degrades 1,25D and 25(OH)D, further worsen cancer progression. Importantly, in
      cells expressing CYP27A1 and/or CYP2R1, which convert inert VD into 25(OH)D, low
      serum VD may reduce intratumoral 25(OH)D synthesis thereby compromising VDR
      antitumoral actions because 25(OH)D can activate the VDR directly and enhance
      1,25D-VDR action. Therefore, this study examined whether abnormal endometrial
      expression of CYP27A1 and/or CYP2R1 may impair VDR-antiproliferative properties
      in endometrial carcinoma (EC). Immunohistochemical analysis of tissue microarrays
      of normal human endometrium (NE; n=60) and EC (n=157) showed the expected lower
      VDR expression in EC (P=0.0002). Instead, CYP24A1 expression was lower in EC
      compared with NE, while CYP27A1 and CYP2R1 expressions were higher (P=0.0002;
      P=0.03). Furthermore, in NE and EC, CYP2R1 and CYP27A1 expression correlated
      directly with nuclear VDR levels, an indicator of ligand-induced VDR activation,
      and inversely with the proliferation marker Ki67. Accordingly, in the
      endometrioid carcinoma cell lines IK, RL95/2 and HEC1-A, which express VDR,
      CYP27A1, and CYP2R1, VD efficaciously reduced cell viability and colony number,
      with a time course that paralleled actual increases in both intracellular 25(OH)D
      and nuclear VDR levels. Thus, VD may protect from EC progression in part through
      increased intratumoral 25(OH)D production by CYP27A1 and CYP2R1 for
      autocrine/paracrine enhancement of 1,25D-VDR-antiproliferative actions. 

PMID- 24732452
TI  - Analysis of MYB oncogene in transformed adenoid cystic carcinomas reveals
      distinct pathways of tumor progression.
AB  - Adenoid cystic carcinomas can occasionally undergo dedifferentiation, a
      phenomenon also referred to as high-grade transformation. However, cases of
      adenoid cystic carcinomas have been described showing transformation to
      adenocarcinomas that are not poorly differentiated, indicating that high-grade
      transformation may not necessarily reflect a more advanced stage of tumor
      progression, but rather a transformation to another histological form, which may
      encompass a wide spectrum of carcinomas in terms of aggressiveness. The aim of
      this study was to gain more insight in the biology of this pathological
      phenomenon by means of genetic profiling of both histological components. Using
      microarray comparative genomic hybridization, we compared the genome-wide DNA
      copy-number changes of the conventional and transformed area of eight adenoid
      cystic carcinomas with high-grade transformation, comprising four with
      transformation into moderately differentiated adenocarcinomas and four into
      poorly differentiated carcinomas. In general, the poorly differentiated carcinoma
      cases showed a higher total number of copy-number changes than the moderately
      differentiated adenocarcinoma cases, and this correlated with a worse clinical
      course. Special attention was given to chromosomal translocation and protein
      expression of MYB, recently being considered to be an early and major oncogenic
      event in adenoid cystic carcinomas. Our data showed that the process of high
      grade transformation is not always accompanied by an accumulation of genetic
      alterations; both conventional and transformed components harbored unique genetic
      alterations, which indicate a parallel progression. Our data further demonstrated
      that the MYB/NFIB translocation is not necessarily an early event or fundamental
      for the progression to adenoid cystic carcinoma with high-grade transformation. 

PMID- 24732453
TI  - Genetic modulation of nephrocalcinosis in mouse models of ectopic mineralization:
      the Abcc6(tm1Jfk) and Enpp1(asj) mutant mice.
AB  - Ectopic mineralization of renal tissues in nephrocalcinosis is a complex,
      multifactorial process. The purpose of this study was to examine the role of
      genetic modulation and the role of diet in nephrocalcinosis using two established
      mouse models of ectopic mineralization, Abcc6(tm1Jfk) and Enpp1(asj) mice, which
      serve as models for pseudoxanthoma elasticum and generalized arterial
      calcification of infancy, two heritable disorders, respectively. These mutant
      mice, when on standard rodent diet, develop nephrocalcinosis only at a very late
      age. In contrast, when placed on an 'acceleration diet' composed of increased
      phosphate and reduced magnesium content, they showed extensive mineralization of
      the kidneys affecting primarily the medullary tubules as well as arcuate and
      renal arteries, as examined by histopathology and quantitated by chemical assay
      for calcium. Mineralization could also be detected noninvasively by micro
      computed tomography. Whereas the heterozygous mice did not develop
      nephrocalcinosis, compound heterozygous mice carrying both mutant alleles,
      Abcc6(tm1Jfk/+) and Enpp1(+/asj), developed ectopic mineralization similar to
      that noted in homozygous mice for either gene, indicating that deletion of one
      Abcc6 allele along with Enpp1 haploinsufficiency resulted in renal
      mineralization. Thus, synergistic genetic defects in the complex
      mineralization/antimineralization network can profoundly modulate the degree of
      ectopic mineralization in nephrocalcinosis. 

PMID- 24732454
TI  - Present status and road map to achieve inclusive and holistic care for dementia
      in a Japanese community: analysis using the Delphi method.
AB  - BACKGROUND/AIMS: Dementia is a priority issue in the public health realm.
      However, few reports address problems of dementia in the real world or provide
      comprehensive road maps to solve these problems. METHODS: Nine groups of
      questions covering 4 topics were discussed using the Delphi method, relating to
      (1) current achievements and challenges regarding inclusive and holistic care in
      the community, (2) patients who are at a high risk of being excluded from care,
      (3) suggestions for a road map for the establishment of better and more inclusive
      medical and social care, and (4) unmet needs of patients with dementia. RESULTS:
      In total, 477 opinions were obtained. Family issues, psychological/behavioral
      symptoms, and complications secondary to physical disorders are main factors for
      being excluded from care. To create a road map for care we have to address the
      topics of reaffirming care principles, multidisciplinary coalitions, and
      education for stakeholders. CONCLUSION: Further effective collaboration to
      promote dementia care is required.

PMID- 24732455
TI  - Identification of pummelo cultivars by using a panel of 25 selected SNPs and 12
      DNA segments.
AB  - Pummelo cultivars are usually difficult to identify morphologically, especially
      when fruits are unavailable. The problem was addressed in this study with the use
      of two methods: high resolution melting analysis of SNPs and sequencing of DNA
      segments. In the first method, a set of 25 SNPs with high polymorphic information
      content were selected from SNPs predicted by analyzing ESTs and sequenced DNA
      segments. High resolution melting analysis was then used to genotype 260
      accessions including 55 from Myanmar, and 178 different genotypes were thus
      identified. A total of 99 cultivars were assigned to 86 different genotypes since
      the known somatic mutants were identical to their original genotypes at the
      analyzed SNP loci. The Myanmar samples were genotypically different from each
      other and from all other samples, indicating they were derived from sexual
      propagation. Statistical analysis showed that the set of SNPs was powerful enough
      for identifying at least 1000 pummelo genotypes, though the discrimination power
      varied in different pummelo groups and populations. In the second method, 12
      genomic DNA segments of 24 representative pummelo accessions were sequenced.
      Analysis of the sequences revealed the existence of a high haplotype polymorphism
      in pummelo, and statistical analysis showed that the segments could be used as
      genetic barcodes that should be informative enough to allow reliable
      identification of 1200 pummelo cultivars. The high level of haplotype diversity
      and an apparent population structure shown by DNA segments and by SNP genotypes,
      respectively, were discussed in relation to the origin and domestication of the
      pummelo species. 

PMID- 24732456
TI  - Private sector provision of oral rehydration therapy for child diarrhea in sub
      Saharan Africa.
AB  - Although diarrheal mortality is cheaply preventable with oral rehydration therapy
      (ORT), over 700,000 children die of diarrhea annually and many health providers
      fail to treat diarrheal cases with ORT. Provision of ORT may differ between for
      profit and public providers. This study used Demographic and Health Survey data
      from 19,059 children across 29 countries in sub-Saharan Africa from 2003 to 2011
      to measure differences in child diarrhea treatment between private for-profit and
      public health providers. Differences in treatment provision were estimated using
      probit regression models controlling for key confounders. For-profit providers
      were 15% points less likely to provide ORT (95% confidence interval [CI] 13-17)
      than public providers and 12% points more likely to provide other treatments (95%
      CI 10-15). These disparities in ORT provision were more pronounced for poorer
      children in rural areas. As private healthcare in sub-Saharan Africa continues to
      expand, interventions to increase private sector provision of ORT should be
      explored.

PMID- 24732457
TI  - Compliance with antimalarial chemoprophylaxis recommendations for wounded United
      States military personnel admitted to a military treatment facility.
AB  - Malaria chemoprophylaxis is used as a preventive measure in military personnel
      deployed to malaria-endemic countries. However, limited information is available
      on compliance with chemoprophylaxis among trauma patients during hospitalization
      and after discharge. Therefore, we assessed antimalarial primary chemoprophylaxis
      and presumptive antirelapse therapy (primaquine) compliance among wounded United
      States military personnel after medical evacuation from Afghanistan (June 2009
      August 2011) to Landstuhl Regional Medical Center in Landstuhl, Germany, and then
      to three U.S. military hospitals. Among admissions at Landstuhl Regional Medical
      Center, 74% of 2,540 patients were prescribed primary chemoprophylaxis and < 1%
      were prescribed primaquine. After transfer of 1,331 patients to U.S. hospitals,
      93% received primary chemoprophylaxis and 33% received primaquine. Of 751 trauma
      patients with available post-admission data, 42% received primary
      chemoprophylaxis for four weeks, 33% received primaquine for 14 days, and 17%
      received both. These antimalarial chemoprophylaxis prescription rates suggest
      that improved protocols to continue malaria chemoprophylaxis in accordance with
      force protection guidelines are needed. 

PMID- 24732458
TI  - Reactivation of mucosal and cutaneous leishmaniasis in a renal transplanted
      patient.
AB  - Mucosal leishmaniasis (ML) is a chronic form of tegumentary leishmaniasis, which
      causes destructive lesions of nasal, pharyngeal, and laryngeal mucosa. We
      describe a case of leishmaniasis reactivation with simultaneous cutaneous and
      mucosal forms in a renal transplanted patient with no history of prior
      leishmaniasis. Reactivation after renal transplantation was not reported in
      Brazil. A 67-year-old woman receiving prednisone 20 mg/day, tacrolimus 1 mg/day,
      and mycophenolic acid 360 mg/day presented with nose edema with erythema and
      cutaneous lesions. Amastigotes were identified on biopsies and the polymerase
      chain reaction confirmed Leishmania (Viannia) braziliensis. The patient was
      treated with liposomal amphotericin B but died 3 weeks after as a result of
      bacterial septic shock. In conclusion, tegumentary leishmaniasis can reactivate
      with simultaneous cutaneous and mucosal forms in a renal transplanted patient
      during the immunosuppressant therapy. 

PMID- 24732459
TI  - A cross-sectional survey of Plasmodium falciparum pfcrt mutant haplotypes in the
      Democratic Republic of Congo.
AB  - In the Democratic Republic of the Congo (DRC), artesunate-amodiaquine is first
      line therapy for falciparum malaria; little is known about the prevalence of
      molecular markers of parasite drug resistance. Across the DRC, we genotyped 166
      parasites in Plasmodium falciparum chloroquine resistance transporter (pfcrt)
      using polymerase chain reaction (PCR) and sequencing. Of these parasites, 73
      (44%) parasites were pure wild-type CVMNK, 55 (31%) parasites were chloroquine
      resistant CVIET: , 35 (21.1%) parasites were mixed CVMNK and CVIET: , and 3
      parasites were other genotypes. Ninety-two infections (55.4%) harbored the pfcrt
      K76T: substitution that is highly correlated with chloroquine failure. The
      amodiaquine-resistant S: VMNT: haplotype was absent. Geographically, pfcrt
      haplotypes were not clearly clustered. Chloroquine accounted for 19.4% of
      antimalarial use, and amodiaquine accounted for 15.3% of antimalarial use; there
      were no associations between drug use and mutant haplotype prevalence. In the
      DRC, our molecular survey indicates that resistance to chloroquine is substantial
      but that resistance to amodiaquine is absent. These contrasting findings
      highlight the need for molecular surveillance of drug resistance to inform
      malaria control policies. 

PMID- 24732460
TI  - Severe neutropenia in dengue patients: prevalence and significance.
AB  - Studies on severe neutropenia in dengue are scarce, and its clinical significance
      is uncertain. We analyzed a cohort of 1,921 reverse transcription polymerase
      chain reaction-confirmed adult dengue patients admitted to the Communicable
      Disease Center in Singapore between 2005 and 2008. Time trend analyses for daily
      absolute neutrophil counts (ANCs) were done using Bayesian hierarchical and
      Markov models. We found that severe neutropenia, defined as ANC <= 0.5 * 10(9)/L,
      was found in 11.8% with a median duration of 1 day. ANC nadir occurred on illness
      day 5. Severe neutropenia was not predictive of more severe disease and not
      associated with secondary bacterial infections, prolonged hospital stay,
      prolonged fever, or fatal outcome. We concluded that prophylactic antibiotics are
      not indicated in patients with severe neutropenia without indication for
      bacterial infection. 

PMID- 24732461
TI  - Heterogeneities in the ecoepidemiology of Trypanosoma cruzi infection in rural
      communities of the Argentinean Chaco.
AB  - We conducted a cross-sectional survey of Trypanosoma cruzi infection of Triatoma
      infestans as well as dogs and cats in 327 households from a well-defined rural
      area in northeastern Argentina to test whether the household distribution of
      infection differed between local ethnic groups (Tobas and Creoles) and identify
      risk factors for host infection. Overall prevalence of infection of bugs (27.2%;
      95% confidence interval = 25.3-29.3%), dogs (26.0%; 95% confidence interval =
      23.3-30.1%), and cats examined (28.7%; 95% confidence interval = 20.2-39.0%) was
      similar. A multimodel inference approach showed that infection in dogs was
      associated strongly with the intensity and duration of local exposure to infected
      bugs and moderately with household ethnic background. Overall, Toba households
      were at a substantially greater risk of infection than Creole households. The
      strong heterogeneities in the distribution of bug, dog, and cat infections at
      household, village, and ethnic group levels may be used for targeted vector and
      disease control. 

PMID- 24732462
TI  - Hepatitis B virus and hepatitis C virus infections in United States-bound
      refugees from Asia and Africa.
AB  - The aim of this study was to determine the prevalence of active hepatitis B and C
      virus infections among refugees from various countries in Africa and Asia. Pre
      admission serum samples collected during 2002-2007 from refugees originating from
      Bhutan (N = 755), Myanmar (N = 1076), Iraq (N = 1137), Laos (N = 593), Thailand
      (N = 622), and Somalia (N = 707) were tested for hepatitis B virus (HBV) DNA and
      hepatitis C virus (HCV) RNA. The HBV DNA (genotypes A, B, C, and G) was detected
      in 12.1% of samples negative for anti-HBs. Highest HBV prevalence was found among
      Hmong; lowest among Bhutanese. The HCV RNA (genotypes 1a, 1b, 1c, 3b, 6n, and 6m)
      was detected in 1.3% of the samples. Highest HCV prevalence was found among Hmong
      from Thailand; lowest among Iraqis. Screening specific refugee groups at high
      risk for viral hepatitis infections will identify infected individuals who could
      benefit from referral to care and treatment and prevent further transmissions. 

PMID- 24732463
TI  - Larval competition extends developmental time and decreases adult size of wMelPop
      Wolbachia-infected Aedes aegypti.
AB  - The intracellular endosymbiont Wolbachia has been artificially transinfected into
      the dengue vector Aedes aegypti, where it is being investigated as a potential
      dengue biological control agent. Invasion of Wolbachia in natural populations
      depends upon the fitness of Wolbachia-infected Ae. aegypti relative to uninfected
      competitors. Although Wolbachia infections impose fitness costs on the adult
      host, effects at the immature stages are less clear, particularly in competitive
      situations. We look for effects of two Wolbachia infections, wMel and wMelPop, on
      intra-strain and inter-strain larval competition in Ae. aegypti. Development of
      Wolbachia-infected larvae is delayed in mixed cohorts with uninfected larvae
      under crowded-rearing conditions. Slow developing wMelPop-infected larvae have
      reduced adult size compared with uninfected larvae, and larvae with the wMel
      infection are somewhat larger and have greater viability relative to uninfected
      larvae when in mixed cohorts. Implications for successful invasion by these
      Wolbachia infections under field conditions are considered. 

PMID- 24732464
TI  - A case of quadruple malaria infection imported from Mozambique to Japan.
AB  - A 35-year-old Japanese man had an intermittent fever and mild headache for eight
      weeks after he returned to Japan from working in Mozambique. He had taken
      antimalarial prophylaxis (doxycycline) for 25 weeks, and stopped taking this drug
      two weeks after his return. Microscopic examination of a peripheral blood smear
      showed a mixed infection with Plasmodium vivax, P. falciparum, and P. ovale. In
      addition, a nested polymerase chain reaction and subsequent sequencing detected
      specific DNA sequences of four species of Plasmodium, including P. malariae. The
      patient was successfully treated with artemether-lumefantrine and primaquine
      phosphate. The present case is a rare instance of a mixed infection with four
      species of Plasmodium. Nonimmune persons in malaria-endemic areas may have a risk
      of mixed infection. All four species must be identified by using sensitive and
      specific tests, such as a nested polymerase chain reaction, in addition to
      conventional morphologic identification. 

PMID- 24732465
TI  - Isolation and molecular identification of Bartonellae from wild rats (Rattus
      species) in Malaysia.
AB  - This study describes our investigation on the prevalence and molecular
      identification of bartonellae from Rattus diardii and R. norvegicus in the urban
      areas of Malaysia. Of 95 rats investigated, Bartonella tribocorum, B.
      rattimassiliensis, B. coopersplainsensis, B. elizabethae, and B. queenslandensis
      were isolated from kidney and spleen homogenates of four rats. Bartonellae DNA
      was amplified from the rat organ tissues by using primers specific for the
      bartonellae RNA polymerase beta subunit (rpoB) gene in nine other rats. Sequence
      analysis of the rpoB gene fragments shows the identification of B.
      queenslandensis in five rats, B. elizabethae in three rats, and B. tribocorum in
      one rat. Combining the results of isolation and molecular detection of
      bartonellae, we found that the prevalence of Bartonella infection in the Rattus
      spp. investigated in this study was 13.7%. Implementation of effective rat
      control program in the urban areas is necessary to prevent the spillover of
      bartonellosis from rats to humans. 

PMID- 24732466
TI  - GAL3 protein expression is related to clinical features of prolactin-secreting
      pituitary microadenoma and predicts its recurrence after surgical treatment.
AB  - BACKGROUND: Previous in vitro study showed that Galectin-3 (Gal-3) protein plays
      an important role in pituitary tumorigenesis, however, the association of Gal-3
      expression with the clinical feature and prognosis of pituitary tumor in a
      clinical setting remains unknown. METHODS: We enrolled 220 patients with
      prolactin-secreting pituitary adenomas (PA) who previously had transsphenoidal
      pituitary surgery. The Gal-3 expression was detected in the patients' PA samples
      using immunohistochemistry and those patients were followed up. A prolactin
      secreting PA cell line, the MMQ cell line, was used to study the in vitro effect
      of Gal-3 on proliferation, migration and invasion of PA cells using small
      interfering RNA (siRNA) transfecton technique. The in vivo tumorgenesis in nude
      mice was also studied. RESULTS: We found that Gal-3 expression was not related to
      age and sex, but positively associated with tumor invasion (P<0.001), tumor sizes
      (P<0.001) and pre-operative prolactin levels (P<0.001). The multivariate Cox
      analysis showed that the Gal-3 expression was closely associated with the
      recurrence of PA after the surgical treatment (HR =3.15, P=0.002). The in vitro
      studies showed that Gal-3 knock-down by the siRNA technique significantly
      inhibited the proliferation, migration and invasion ability of the MMQ cells,
      whereas Gal-3 siRNA transfection induced apoptosis of the MMQ cells. The in vivo
      tumorgenesis assay showed that Gal-3 siRNA transfection significantly inhibited
      the tumor volume in vivo compared to transfection of the control siRNA (P<0.001).
      CONCLUSION: Gal-3 regulates proliferation, apoptosis, migration and invasion of
      the MMQ cells. Gal-3 may be used as a tissue marker to evaluate the clinical
      feature and prognosis of PA patients.

PMID- 24732468
TI  - Strain-induced enhancement of plasma dispersion effect and free-carrier
      absorption in SiGe optical modulators.
AB  - The plasma dispersion effect and free-carrier absorption are widely used to
      change refractive index and absorption coefficient in Si-based optical
      modulators. However, the weak free-carrier effects in Si cause low modulation
      efficiency, resulting in large device footprint and power consumption. Here, we
      theoretically and experimentally investigate the enhancement of the free-carrier
      effects by strain-induced mass modulation in silicon-germanium (SiGe). The
      application of compressive strain to SiGe reduces the conductivity effective mass
      of holes, resulting in the enhanced free-carrier effects. Thus, the strained SiGe
      based optical modulator exhibits more than twice modulation efficiency as large
      as that of the Si modulator. To the best of our knowledge, this is the first
      demonstration of the enhanced free-carrier effects in strained SiGe at the near
      infrared telecommunication wavelength. The strain-induced enhancement technology
      for the free-carrier effects is expected to boost modulation efficiency of the
      most Si-based optical modulators thanks to high complementary metal-oxide
      semiconductor (CMOS) compatibility. 

PMID- 24732469
TI  - Development of a Virtual Reality Simulator for Natural Orifice Translumenal
      Endoscopic Surgery (NOTES) Cholecystectomy Procedure.
AB  - The first virtual-reality-based simulator for Natural Orifice Translumenal
      Endoscopic Surgery (NOTES) is developed called the Virtual Translumenal
      Endoscopic Surgery Trainer (VTEST<sup>TM</sup>). VTEST<sup>TM</sup> aims to
      simulate hybrid NOTES cholecystectomy procedure using a rigid scope inserted
      through the vaginal port. The hardware interface is designed for accurate motion
      tracking of the scope and laparoscopic instruments to reproduce the unique hand
      eye coordination. The haptic-enabled multimodal interactive simulation includes
      exposing the Calot's triangle and detaching the gall bladder while performing
      electrosurgery. The developed VTEST<sup>TM</sup> was demonstrated and validated
      at NOSCAR 2013. 

PMID- 24732470
TI  - Computer-based Planning System for Mandibular Reconstruction.
AB  - Mandibular reconstruction is typically performed for traumatic or postsurgical
      conditions, and may involve the use of autologous osteocutaneous fibula free
      flaps for large defects. Recreating the native contour of the mandible during
      reconstructive surgery is challenging. Existed pre-operative planning software
      has limitations. In this paper we present a novel pre-operative planning system
      that helps to optimize the number and location of bony osteotomies, and the
      orientation of the harvested bone segments by specifically prioritizing the
      position and number of the cutanteous perforators to the osteocutaneous fibula
      free flap, in order to improve the reliability of the osteocutaneous fibula free
      flap. 

PMID- 24732467
TI  - IGF2 ameliorates amyloidosis, increases cholinergic marker expression and raises
      BMP9 and neurotrophin levels in the hippocampus of the APPswePS1dE9 Alzheimer's
      disease model mice.
AB  - The development of an effective therapy for Alzheimer's disease (AD) is a major
      challenge to biomedical sciences. Because much of early AD pathophysiology
      includes hippocampal abnormalities, a viable treatment strategy might be to use
      trophic factors that support hippocampal integrity and function. IGF2 is an
      attractive candidate as it acts in the hippocampus to enhance memory
      consolidation, stimulate adult neurogenesis and upregulate cholinergic marker
      expression and acetylcholine (ACh) release. We performed a seven-day
      intracerebroventricular infusion of IGF2 in transgenic APPswe.PS1dE9 AD model
      mice that express green fluorescent protein in cholinergic neurons
      (APP.PS1/CHGFP) and in wild type WT/CHGFP littermates at 6 months of age
      representing early AD-like disease. IGF2 reduced the number of hippocampal
      Abeta40- and Abeta42-positive amyloid plaques in APP.PS1/CHGFP mice. Moreover,
      IGF2 increased hippocampal protein levels of the ACh-synthesizing enzyme, choline
      acetyltransferase in both WT/CHGFP and APP.PS1/CHGFP mice. The latter effect was
      likely mediated by increased protein expression of the cholinergic
      differentiating factor, BMP9, observed in IGF2-treated mice as compared to
      controls. IGF2 also increased the protein levels of hippocampal NGF, BDNF, NT3
      and IGF1 and of doublecortin, a marker of neurogenesis. These data show that IGF2
      administration is effective in reversing and preventing several pathophysiologic
      processes associated with AD and suggest that IGF2 may constitute a therapeutic
      target for AD. 

PMID- 24732471
TI  - Toward the development of a virtual electrosurgery training simulator.
AB  - We propose a principled approach to the design of a computer-based, virtual
      reality simulator specifically for electrosurgical training. The design builds on
      the Fundamental Use of Surgical Energy (FUSE) program's didactic curriculum and
      the results of a survey of domain experts on the roles of cognitive knowledge and
      hands-on training for a selection of electrosurgery tasks. The resulting design
      focuses narrowly on the tissue effects caused during electrosurgery and the
      identified physician-controllable factors causing those effects. 

PMID- 24732472
TI  - Patient-specific pipeline to create virtual endoscopic third ventriculostomy
      scenarios.
AB  - Graphically realistic, haptics-enabled, virtual reality surgical simulations are
      becoming increasingly popular training tools for neurosurgical procedures and
      surgical skills. Compared with traditional training models, virtual simulations
      are safe, versatile, consistent, and are relatively cost effective. Most
      simulations are deficient, however, in representing the diverse anatomical
      variations that occur clinically. In this work, we describe the design and
      implementation of a pipeline to create patient-specific surgical scenarios for
      simulator-based training of the endoscopic third ventriculostomy: the procedure
      of choice for treating obstructive hydrocephalus. 

PMID- 24732473
TI  - Modular simulator building blocks: physiologic signaling requirements.
AB  - Embedded microcontroller hardware has matured to the point that organ- and system
      specific modules that can be assembled in various configurations are practical.
      Our work developing and interconnecting organ and system modules in the
      cardiovascular and pulmonary systems illustrates the signaling requirements
      necessary to fully leverage the technology. It also highlights the need for
      standard signaling protocols that parallel those under development for software
      centric physiology simulation systems. 

PMID- 24732474
TI  - Application of learning record stores and other forms of electronic competency
      records in modeling competency degradation.
AB  - In the context of cognitive competencies, we are defined by our memories. As
      such, experiential data in various forms of Electronic Competency Records (ECRs),
      including the Learning Record Store (LRS), can be used as the basis for an
      Intelligent Tutoring System (ITS), scheduling medical recertification preparation
      and other forms of educational intervention. However, the experiential data
      infrastructure provided by an ECR is necessary but insufficient for realizing the
      full potential of competency tracking and prediction technology. To this end, we
      are exploring competency degradation models based on time and interference, using
      retrospective data from our ECR-based work in ITS. 

PMID- 24732475
TI  - Computation and visualization of risk assessment in deep brain stimulation
      planning.
AB  - Deep Brain Stimulation is aneurosurgical approach for the treatment of
      pathologies such as Parkinson's disease. The basic principle consists in placing
      a thin electrode in a deep part of the brain. To safely reach the target of
      interest, careful planning must be performed to ensure that no vital structure
      (e.g. blood vessel) will be damaged during the insertion of the electrode.
      Currently this planning phase is done without considering the brain shift, which
      occurs during the surgery once the skull is open, leading to increased risks of
      complications. In this paper, we propose a method to compute the motion of
      anatomical structures induced by the brain shift. This computation is based on a
      biomechanical model of the brain and the cerebro-spinal fluid. We then visualize
      in a intuitive way the risk of damaging vital structures with the electrode. 

PMID- 24732476
TI  - An ultrasound-based navigation system for minimally invasive neck surgery.
AB  - Future minimally invasive neck surgery requires a navigation system adapted to
      the actual intra-operative bedding of the patient. The detection of the bedding
      caused tissue shift is essential for a safe orientation for the surgeon new
      endoscopic operation procedures in neck surgery. It is essential to visualize the
      relation between important anatomic landmarks and operation instruments at any
      time. Within the scientific project SACAS we focus on developing an ultrasound
      supported navigation system based on preoperative imaging which considers the
      intra-operative tissue shift. A rotatable, flexible neck-model provides the basis
      for our analysis to evaluate the tissue shift and to invent the new navigation
      system for endoscopic neck surgery. The total registration error of the system
      was 2 mm. 

PMID- 24732477
TI  - Virtual reality for improving body image disorders and weight loss after gastric
      band surgery: a case series.
AB  - Laparoscopic Adjustable Gastric Banding (LAGB) is a common surgery method used to
      help obese patients to lose weight. However, even if LAGB is able to produce a
      durable and relevant weight loss, it is less effective in improving body image:
      as demonstrated by a recent study, obese patients with a body image disorder in
      the pre-operative stage continue to show this even 13 months after the operation.
      In this presentation we will discuss the possible role of virtual reality (VR) in
      addressing this problem within an integrated cognitive behavioral approach. To
      test this approach, a case series of three LAGB patient who experienced body
      dissatisfaction even after a >30/40% excess body weight loss, is presented and
      discussed. At the end of the 6-week protocol the patients experienced a 15%-20%
      further reduction of their weight. This reduction was also matched by a general
      improvement of the psychological state. Both the weight loss and the level of
      well-being were further improved after a three-month follow-up. 

PMID- 24732478
TI  - Do not forget the oldest old: design principles for the 80+.
AB  - A significant amount of research has been conducted regarding the design of
      Internet applications for the elderly. Concomitantly, researchers have been
      applying online technologies to healthcare for older adults. The oldest old (for
      our purposes, defined as older adults aged 80+) are increasingly adopting the use
      of the Internet and likely have different needs than those who are between 55 and
      80 years old. The main results from a literature review on the existing research
      in human factors and design for older adults is presented. These results
      highlight the need for more research in human factors and design in the much
      neglected population group, the oldest old. 

PMID- 24732479
TI  - Developing clinically relevant aspects of the nuss procedure surgical simulator.
AB  - Surgical simulators can avail minimizing the risk of surgery and help achieving a
      better outcome. This is also the case for the Nuss procedure, a minimally
      invasive surgery for correcting pectus excavatum (PE) - a congenital chest wall
      deformity. A simulator can be of great benefit if it provides realistic behavior
      and representation of the actual surgery. In this paper, we address various
      clinical aspects of the procedure for a training simulation, reproducing a
      virtual model of the patient's thoracic cavity and internal organs with realistic
      textures, as well as physical behaviors. In addition, a high fidelity haptic
      force feedback system is constructed to provide the surgeon with a close-to-real
      sensation while interacting with the virtual model. 

PMID- 24732480
TI  - Navigated simulator for spinal needle interventions.
AB  - We present a navigated simulator for ultrasound-guided spine needle
      interventions, comprising of an ultrasound scanner, tracking system, surgical
      instruments, tissue-mimicking spine phantom, and augmented virtuality navigation
      platform. The ultrasound transducer, spine needle, and spine phantom are
      magnetically tracked and spatially calibrated, allowing the navigation software
      to render the surgical scene with streaming ultrasound video in 3D. The spine
      phantom provides sonoanatomically correct images, with realistic tactile
      sensation from needle advancement through tissues layers. The combination of a
      physical phantom and navigation software provides a realistic, inexpensive, and
      interactive environment for teaching and learning, the latter also having
      potential as an interventional tool for real-time ultrasound-guided spine needle
      insertion. 

PMID- 24732481
TI  - Automatic detection of inferior alveolar nerve canal from cone-beam computed
      tomography images for dental surgery planning.
AB  - The inferior alveolar nerve canal is an important nerve canal in the jaw bone,
      and any damage to this canal can cause pain or fatal complications. Since such
      damage can be caused by a wrong surgical procedure or surgery plan, accurate
      surgery planning is necessary. Cone-beam computed tomography (CBCT) is a three
      dimensional medical imaging method that is mainly used in dental treatment;
      however, identifying the nerve canal is difficult in CBCT images as compared to
      conventional CT images. This paper proposes a new concept of a panoramic curve
      for nerve canal detection and a detection algorithm that is usually applied to
      facial recognition was introduced in this study for the automatic detection of
      nerve canal in CBCT images. 

PMID- 24732482
TI  - A virtual reality platform for assessment and rehabilitation of neglect using a
      kinect.
AB  - Unilateral Spatial Neglect (USN) is normally assessed with paper-and-pencil
      tests. Virtual reality can be an effective neuropsychological tool for a more
      ecological and functional assessment and rehabilitation of neglect. We developed
      a 3D Virtual Reality platform - NeuroVirtual 3D - for the assessment and
      rehabilitation of cognitive deficits, in particular for USN. Within the virtual
      environments it is possible to interact with virtual objects and execute specific
      exercises using a Microsoft Kinect. Through the analysis of different grasping
      tasks it is possible to evaluate in an ecological way the patients' ability to
      find and handle objects in both sides of the virtual space. 

PMID- 24732483
TI  - Outside Observer, an Enhanced Training Methodology: Bringing Back the Expert's
      Eye whilst Training Alone.
AB  - Traditional surgical teaching requires an expert trainer to be present during
      training. This training model allows an expert to observe a novice's performance
      and provide corrective feedback as errors are made. Virtual simulations offer a
      much needed alternative to learning through error and allow the trainee to hone
      skills without the presence of a skilled surgical trainer. However, current
      simulations limit the scope of training to tool directed learning, focusing
      training around instrumented simulated tool tips. This paper identifies a need
      for trainee centered virtual training to complement current approaches. The
      Outside Observer training methodology provides training feedback based on the
      observation of surgical tool tip manipulations in conjunction with the external
      movements a trainee performs during a procedure. It is thought that integrating
      movement and posture training with current tool tracking methods will provide
      more effective and accelerated learning. 

PMID- 24732484
TI  - Constraint-based simulation for non-rigid real-time registration.
AB  - In this paper we propose a method to address the problem of non-rigid
      registration in real-time. We use Lagrange multipliers and soft sliding
      constraints to combine data acquired from dynamic image sequence and a
      biomechanical model of the structure of interest. The biomechanical model plays a
      role of regularization to improve the robustness and the flexibility of the
      registration. We apply our method to a pre-operative 3D CT scan of a porcine
      liver that is registered to a sequence of 2D dynamic MRI slices during the
      respiratory motion. The finite element simulation provides a full 3D
      representation (including heterogeneities such as vessels, tumor,...) of the
      anatomical structure in real-time. 

PMID- 24732485
TI  - Using Virtual World Training to Increase Situation Awareness during
      Cardiopulmonary Resuscitation.
AB  - Situation awareness (SA) is a critical non-technical skill which affects outcome
      during emergency medical endeavors. Using a modified self-report instrument a
      significant increase of SA was found during multiplayer virtual world CPR team
      training among 12 medical students. Further a correlation between SA and
      attention was noted. Being a vital factor during the process of video-game play,
      we argue that this skill is suitably practiced using this training method. 

PMID- 24732486
TI  - A Decoupled 2 DOF Force Feedback Mechanism for the Virtual Translumenal
      Endoscopic Surgical Trainer (VTEST.
AB  - Natural orifice translumenal endoscopic surgery (NOTES) is a minimally invasive
      procedure which utilizes the body's natural orifices to gain access to the
      peritoneal cavity. The VTEST is a virtual reality NOTES cholecystectomy simulator
      being built at the CeMSIM at RPI. We have developed a 2 DOF decoupled haptic
      device, which can provide translational and rotational haptic feedback to the
      user handling the flexible endoscope. Preliminary results indicate the device is
      capable of providing realistic feedback to the user while operating the device. 

PMID- 24732487
TI  - The evolution of design: a novel thoracoscopic diaphragmatic hernia repair
      simulator.
AB  - As advanced minimally invasive techniques have become more prevalent, there has
      been an increase in the number of pediatric surgeons performing thoracoscopic
      repair of congenital diaphragmatic hernia (CDH). Opportunities to learn and
      practice this procedure are few. The use of a simulation model for thoracoscopic
      CDH repair may help reduce errors in the operating room. Prototypes for low and
      high fidelity CDH repair simulators were designed and built. These prototypes
      allow pediatric surgery trainees the opportunity to learn and practice
      thoracoscopic CDH repair before performing this operation on infants. 

PMID- 24732488
TI  - Overall wrist biomechanics are conserved by phenol-based embalming.
AB  - Although cadaveric specimens that have been fresh-frozen then thawed are
      considered the gold standard for biomechanics research, because they most closely
      represent in vivo tissues, potential problems include a relatively short useful
      time-span and risk of infection. A recently reported new method of phenol-based
      "soft" embalming has been found to preserve tissues in a fresh-like state over an
      extended period of time and simultaneously reduced infection risks. This study
      presents radio-ulnar deviation end-range data from 4 soft-embalmed and
      refrigerated human cadaveric forearm specimens over 12 months. All end-range
      comparisons were found to be statistically equivalent to within a clinically
      acceptable range of +/-5 degrees of radio-ulnar deviation with a 95% con. dence
      measure of p < 0.01 in every case. These soft-embalmed specimens provide
      promising results for further use in biomechanical studies. 

PMID- 24732489
TI  - Development of a Tele ENT Program to Support Distant Military Treatment
      Facilities for the European Regional Medical Command.
AB  - Two hundred forty-five thousand patients seek care at Landstuhl Regional Medical
      Center. They battle lengthy commutes, costly procedures, and limited specialty
      care in order to consult their physicians. Implementing telemedical procedures at
      hospitals such at LRMC is believed to reduce travel time, decrease costs, and
      increase specialization. Healthcare providers who were trained in Tele ENT
      procedures unanimously accepted the technology as an alternative way to care for
      patients. Expansion of telemedical procedures in hospitals is deemed to reduce
      health care costs and to be accepted by providers. 

PMID- 24732490
TI  - An Image-based Multiproxy Palpation Algorithm for Patient-Specific VR-Simulation.
AB  - Palpation is the first step for many medical interventions. To provide an
      immersive virtual training and planning environment, the palpation step has to be
      successfully modeled and simulated. Here, we present a multiproxy approach that
      calculates friction and surface resistance forces for multiple contact points on
      finger tips or virtual tools like ultrasound probes and displays the resulting
      force and torque on a 6DOF haptic device. No manual or time intensive
      segmentation of patient image data is needed to create a simulation based on CT
      data and thus our approach is usable for patient-specific simulation of
      palpation. 

PMID- 24732491
TI  - A decision support system for real-time stress detection during virtual reality
      exposure.
AB  - Virtual Reality (VR) is increasingly being used in combination with psycho
      physiological measures to improve assessment of distress in mental health
      research and therapy. However, the analysis and interpretation of multiple
      physiological measures is time consuming and requires specific skills, which are
      not available to most clinicians. To address this issue, we designed and
      developed a Decision Support System (DSS) for automatic classification of stress
      levels during exposure to VR environments. The DSS integrates different biosensor
      data (ECG, breathing rate, EEG) and behavioral data (body gestures correlated
      with stress), following a training process in which self-rated and clinical-rated
      stress levels are used as ground truth. Detected stress events for each VR
      session are reported to the therapist as an aggregated value (ranging from 0 to
      1) and graphically displayed on a diagram accessible by the therapist through a
      web-based interface. 

PMID- 24732492
TI  - PATIENT: Physical Anatomical Trainer Instrumented for Education and Non
      Subjective Testing.
AB  - The PATIENT manikin (Physical Anatomical Trainer Instrumented for Education and
      Non-subjective Testing) is designed with the conflicting needs of a highly
      modular system for ultimate scenario flexibility and cost containment, and a
      highly realistic system. PATIENT provides a unique combination of capital and
      disposable components, with each organ treated as a limited-reuse component. The
      organs contain unobtrusive instrumentation which informs the PATIENT control unit
      of the organ status. The control unit can adjust whole-body parameters to reflect
      the local physiology. PATIENT enables tailored simulations, from Point of Injury
      training of basic life support, through hospital training including surgical
      interventions. 

PMID- 24732493
TI  - Simulation fidelity: more than experience and mere repetition?
AB  - Our understanding and use of simulation based training has evolved from simply
      practicing or learning performance in an accurate re-creation of the operating
      room as first envisaged by anaesthetist simulation pioneers. The efficacy of
      simulation training has been quantitatively demonstrated in prospective,
      randomized, double blinded studies. Simulation training models used in these
      studies have varied from bespoke models for training intra-corporeal suturing
      skills, VR emulation models for basic laparoscopic skill acquisition through to
      full physics VR simulations for the learning of endovascular skills. The
      understanding of why specific simulation models are effective needs to be better
      understood by trainers, researchers and engineers if simulation based training is
      to deliver on its potential for more advanced skills training but more
      importantly for the acquisition of procedural wisdom. This development will
      require a better understanding and more forthright approach to the issue of
      simulation fidelity. 

PMID- 24732494
TI  - Raven surgical robot training in preparation for da vinci.
AB  - The rapid adoption of robotic assisted surgery challenges the pace at which
      adequate robotic training can occur due to access limitations to the da Vinci
      robot. Thirty medical students completed a randomized controlled trial evaluating
      whether the Raven robot could be used as an alternative training tool for the
      Fundamentals of Laparoscopic Surgery (FLS) block transfer task on the da Vinci
      robot. Two groups, one trained on the da Vinci and one trained on the Raven, were
      tested on a criterion FLS block transfer task on the da Vinci. After robotic FLS
      block transfer proficiency training there was no statistically significant
      difference between path length (p=0.39) and economy of motion scores (p=0.06)
      between the two groups, but those trained on the da Vinci did have faster task
      times (p=0.01). These results provide evidence for the value of using the Raven
      robot for training prior to using the da Vinci surgical system for similar tasks.

PMID- 24732495
TI  - Real-time passive tracking for multi-touch medical modeling and simulation.
AB  - The military medical community expects to minimize use of live tissue and
      cadavers for training purposes. This research demonstrates an innovative use of
      synthetic tissue and passive tracking computer vision to create a real-time,
      interactive environment for training medical staff. 

PMID- 24732496
TI  - Commercial videoconferencing for use in telementoring laparoscopic surgery.
AB  - Telementoring is a useful tool for laparoscopic surgical education. However,
      current systems have high barriers to entry that prevent widespread adoption.
      Using commercial videoconferencing applications for telementoring would lower
      cost and technical barriers. This study examines nine of these options. 

PMID- 24732497
TI  - pWeb: A High-Performance, Parallel-Computing Framework for Web-Browser-Based
      Medical Simulation.
AB  - This work presents a pWeb - a new language and compiler for parallelization of
      client-side compute intensive web applications such as surgical simulations. The
      recently introduced HTML5 standard has enabled creating unprecedented
      applications on the web. Low performance of the web browser, however, remains the
      bottleneck of computationally intensive applications including visualization of
      complex scenes, real time physical simulations and image processing compared to
      native ones. The new proposed language is built upon web workers for
      multithreaded programming in HTML5. The language provides fundamental
      functionalities of parallel programming languages as well as the fork/join
      parallel model which is not supported by web workers. The language compiler
      automatically generates an equivalent parallel script that complies with the
      HTML5 standard. A case study on realistic rendering for surgical simulations
      demonstrates enhanced performance with a compact set of instructions. 

PMID- 24732498
TI  - Design and development of a laparoscopic gastrostomy tube placement simulator.
AB  - Laparoscopic gastrostomy tube placement is a common surgical procedure performed
      in infants. There are currently no commercially available simulation tools for
      pediatric surgeons to use for surgical training and practice purposes. We have
      created a low cost and reusable laparoscopic gastrostomy tube placement model for
      use in pediatric surgical education. 

PMID- 24732499
TI  - Design and development of low-cost tissue replicas for simulation of rare
      neonatal congenital defects.
AB  - Studies have shown that simulation can be a valuable tool for training pediatric
      surgeons to perform thoracoscopic repair of rare congenital anomalies [1-3]. The
      previously evaluated models were high fidelity, hybrid models that required the
      use of fetal bovine or porcine tissue blocks within a simulated neonate chest
      cavity. Real tissue blocks can be expensive, and may not be readily available in
      some parts of the world. We have developed low-cost, portable simulators for
      esophageal atresia with tracheoesophageal fistula (EA/TEF) and duodenal atresia
      (DA) that recreate the 3-dimensional challenges for minimally invasive repair.
      These are fully simulated models of the thoracic and abdominal cavities
      containing synthetic tissue that replicates the required anatomy. 

PMID- 24732500
TI  - A matrix lie group approach to statistical shape analysis of bones.
AB  - Statistical shape models using a principal-component analysis are inadequate for
      studying shapes that are in non-linear manifolds. Principal tangent components
      use a matrix Lie group that maps a non-linear manifold to a corresponding linear
      tangent space. Computations that are performed on the tangent space of the
      manifold use linear statistics to analyze non-linear shape spaces. The method was
      tested on bone surface from proximal femurs. Using only three components, the new
      model recovered 94% of the medical dataset, whereas a conventional method that
      used linear principal components needed 24 components to achieve the same
      reconstruction accuracy. 

PMID- 24732501
TI  - Virtual laparoscopic surgical skills practice using a multi-degree of freedom
      joystick.
AB  - The objective of this study was to compare three different surgical skills
      practice environments while performing a virtual laparoscopic surgical training
      task using a multi-degree of freedom joystick, a commercial manipulator or a
      training box. Nine subjects performed a virtual peg transfer task and their upper
      extremity muscle effort and fatigue were measured. The results demonstrated a
      similar muscle effort and fatigue of the upper extremity among the three training
      environments. Subjects with medical backgrounds used significantly higher muscle
      effort when they performed the training task using the joystick than the
      manipulator, but used similar muscle effort between the joystick and the training
      box. This study suggests that the multi-degree of freedom joystick could provide
      more options to practice virtual laparoscopic surgical training tasks with muscle
      effort and fatigue similar to other traditional training boxes. 

PMID- 24732502
TI  - Virtual humans for inter-ethnic variability training in sedation and analgesia.
AB  - The objective of this research is to enable realistic Virtual Humans (VH) that
      support inter-ethnic variability training. Inter-ethnic variability refers to
      differences in response to medical treatment, such as drug administration, due to
      ethnicity (e.g., Caucasian, African American, or South Asian). Most current
      approaches to VHs do not model these differences. Our approach consists of
      driving VH responses based on a real time pharmacodynamic / pharmacokinetic
      propofol model that includes inter-ethnic variability. Results of a user study
      with 22 medical students suggest that utilizing VHs for inter-ethnic variability
      training is feasible and can increase awareness of inter-ethnic variability. 

PMID- 24732503
TI  - Self-Reported Differences in Personality, Emotion Control, and Presence Between
      Pre-Military and Non-Military Groups in a Pilot Study Using the Stress Resilience
      in Virtual Environments (STRIVE) System.
AB  - Mental health disorders are the signature wounds of war resulting from extended
      U.S. Military conflicts in the Middle East [1]. In an effort to abate the number
      of Service Members that develop mental health disorders in these conflicts, USC
      ICT has created the Stress Resilience in Virtual Environments (STRIVE) project, a
      set of highly realistic virtual reality combat scenarios and resilience-building
      sessions designed for pre-deployed military personnel. This short-paper looks at
      self-reported differences in personality, emotion control, and presence between
      two different groups, pre-military and non-military, of pilot subjects that
      tested a prototype of the first four modules of STRIVE. 

PMID- 24732504
TI  - Unobtrusive augmentation of critical hidden structures in laparoscopy.
AB  - A fundamental problem in implementing augmented reality (AR) surgery is
      characterizing how visualizations effect surgeon perception. This problem is
      important because procedure outcomes depend on surgeon ability to perceive hidden
      and visible structure interrelation which may be quite dynamic. AR techniques
      such as x-ray vision are designed to compensate for or reintroduce depth cues
      lost overlaying hidden structures on a view stream. Such enhancements are
      necessarily deviations, which may obtrude. This paper provides discussion of
      hidden structure rendering, analysis, a proposed framework, protocol and
      experiment (n=2500) for safe evaluation within in vitro laparoscopic video from,
      and minimal transfer to, in vivo surgery. Results evidence our protocol enables
      comparison of hidden structure visualizations on task efficacy in vitro and
      suggest promising new direction towards validating AR in live surgery. 

PMID- 24732505
TI  - Evaluation of haptic teaching approaches for laparoscopic surgery training.
AB  - Laparoscopic surgery, one type of minimally invasive surgery (MIS) is a very
      important surgery technique which requires advanced surgical technique. At
      present, expert one-on-one teaching mainly supports the training of these
      advanced surgical techniques. However, time constraints prevent experts spending
      the amount of time desired for this training. Therefore, we aim to support
      training using a VR-based laparoscopic surgery simulator equipped with a guidance
      force display. This increases the amount of training a trainee can avail of while
      at the same time allow the expert and the trainee to increase the quality of the
      limited one-to-one time together. The first step of our research is to
      investigate approaches that displays the guidance force to teach experts hand
      movements. In this study, we used two guidance force-display approaches:
      Instrument-guiding approach and Hand-guiding approach. Through evaluative
      experiments, we found that the Hand-guiding approach is more suitable for skill
      transfer than the Instrument-guiding approach in particular tasks. The results
      are described below. 

PMID- 24732506
TI  - Open Surgical Simulation (OSS) - A Community Resource.
AB  - The OpenSurgSim system (www.opensurgsim.org) has been in development for the past
      18 months. This open-source system is designed to provide the foundation for
      development of surgical simulators. The system combines years of learning the ins
      and outs of simulator design with best practices from other successful open
      source projects. 

PMID- 24732507
TI  - Evaluation of a mobile augmented reality application for image guidance of
      neurosurgical interventions.
AB  - Image guidance can provide surgeons with valuable contextual information during a
      medical intervention. Often, image guidance systems require considerable
      infrastructure, setup-time, and operator experience to be utilized. Certain
      procedures performed at bedside are susceptible to navigational errors that can
      lead to complications. We present an application for mobile devices that can
      provide image guidance using augmented reality to assist in performing
      neurosurgical tasks. A methodology is outlined that evaluates this mode of
      visualization from the standpoint of perceptual localization, depth estimation,
      and pointing performance, in scenarios derived from a neurosurgical targeting
      task. By measuring user variability and speed we can report objective metrics of
      performance for our augmented reality guidance system. 

PMID- 24732508
TI  - 3D Simulation of a Hospital Environment and Ward Round to Augment a Summer School
      Program for Pre-Medical Students.
AB  - Students applying to medical school may benefit from a better understanding of
      the clinical environment and the duties of a doctor. Despite attachments at
      hospital they may feel detached from the decision making process which is a
      pivotal part of being a clinician. A simulated hospital environment was tried on
      30 pre-med students from an urban environment to test the feasibility of using
      structured clinical scenarios to augment their experience of a clinical setting. 

PMID- 24732509
TI  - Tele-MFAsT: Kinect-Based Tele-Medicine Tool for Remote Motion and Function
      Assessment.
AB  - We present work-in-progress on framework for 3D Kinect-based remote motion and
      function assessment. Tele-MFAsT facilities streaming of data (video, depth,
      skeleton, and audio) from network-connected Microsoft Kinect cameras that can be
      utilized to observe a patient remotely during function assessment by a physician
      or therapist, measure motion trajectories, and joint angles, while taking
      advantage of tele-presence in a 3D virtual environment. The network architecture
      also allows for integration with wireless sensors in the future. In this paper we
      describe Tele-MFAsT application for upper-body range of motion measurements. 

PMID- 24732510
TI  - Modification of the pelvic examination simulator for the developing world.
AB  - The clinical pelvic exam is a critical examination for external and internal
      inspection of female reproductive organs. A sensor enabled pelvic examination
      simulator was developed to provide immediate visual performance feedback. The
      simulator was modified for rural area usage, where electricity supply and PC
      display may not be available. We succeeded at replacing key components while
      maintaining functionality. 

PMID- 24732511
TI  - Validity of a Newly Developed Tri-axial Sensor for Clinical Breast Examination
      Skills Assessment.
AB  - The clinical breast examination is a critical exam for early detection of breast
      cancer. Assessment methods are needed to determine competency and skill mastery
      for experts and novices. The 3D sensor was developed to capture hand shear and
      normal forces conducted during an exam. Trials were conducted to record
      exploratory maneuvers used during the exam. The sensor system was found to be a
      reliable method for capturing exploratory maneuvers. 

PMID- 24732512
TI  - Application of a new adaptable thyroid model for ultrasound and hands-on skill
      assessment.
AB  - The thyroid exam is an important clinical skill that is widely practiced by both
      primary care and specialty physicians. Despite this, there are few teaching
      models that allow for practice and assessment of proper examination technique. We
      developed a sensorized thyroid exam model and accompanying survey to capture
      clinical decision making and hands-on performance. Two endocrinologists performed
      the thyroid exam on the models. There was verbal consensus on clinical findings;
      however estimates on thyroid properties and size differed. Additional experiments
      with an ultrasound provided feedback on use of the model for hands-on and
      ultrasound-based examinations. 

PMID- 24732513
TI  - From trauma in austere environments to combat or medical school: how blended
      hyper-realism in the real and virtual worlds can better prepare surgeons.
AB  - Surgical and simulation development have always been closely associated with
      military activity. The last ten years have continued that trend, allowing for
      training in real time, under reality-based conditions, learning technical and
      clinical skills with the dynamic of true human factors and team training in the
      actual environment. We present data from diverse activities in three separate
      scenarios: second-year medical students in clinical scenarios; the U.S. Ski Team
      physicians training in austere conditions; the U.S. Navy Fleet Surgical Team
      training for sea and land deployment. 

PMID- 24732514
TI  - Multimodality approach to classifying hand utilization for the clinical breast
      examination.
AB  - The clinical breast examination (CBE) is performed to detect breast pathology.
      However, little is known regarding clinical technique and how it relates to
      diagnostic accuracy. We sought to quantify breast examination search patterns and
      hand utilization with a new data collection and analysis system. Participants
      performed the CBE while the sensor mapping and video camera system collected
      performance data. From this data, algorithms were developed that measured the
      number of hands used during the exam and active examination time. This system is
      a feasible and reliable method to collect new information on CBE techniques. 

PMID- 24732515
TI  - Development of Extracorporeal Suturing Simulation in Virtual Basic Laparoscopic
      Skill Trainer (VBLaST.
AB  - This paper presents the development of extracorporeal suturing simulation in
      Virtual Basic Laparoscopic Skill Trainer (VBLaST<sup>(c)</sup>). A novel hardware
      interface is designed to allow the user to perform the physical action of trying
      a knot and seamlessly integrate the knot into the virtual simulation. 

PMID- 24732516
TI  - 3D++ Visualisation of MEBN Graphs and Screen Representations of Patient Models
      (PIXIE II).
AB  - The aim of this study is to investigate modelling- and visualisation methods and
      tools for transparent, reproducible and comprehensible information management of
      patient probabilistic graphical models such as Multi-Entity Bayesian Networks
      (MEBN). In therapy planning environments, models provide the knowledge base to
      assist physicians in their decision making process and are typically at the heart
      of a networked information system. The topic of user interface design (UID) and
      specifically GUIs needs to be addressed in this context in a very creative
      manner, if the aim is to make complex models easier for the user to understand
      and to manage. As a basis for preparing a demonstration to show a proof of
      concept for the visualisation of MEBNs, the visualization tool called "ANTz" is
      being proposed here and used as the preferred visualisation tool. 

PMID- 24732517
TI  - Personal training simulator for asynchronous learning of obstetric ultrasound.
AB  - To meet the challenges of providing affordable, efficient ultrasound training, a
      low-cost, portable personal ultrasound training simulator with structured
      curriculums and integrated assessment methods has been developed. By using
      extended image volumes for training, the realistic experience of scanning over a
      larger body surface is emulated. 

PMID- 24732519
TI  - Ultrasound-stimulated vibro-acoustography for high-resolution differentiation
      based on viscoelastic properties of tissue mimicking phantoms.
AB  - In the absence of an imaging technique that provides imagery of diseased tissue
      with high diagnostic accuracy and contrast, surgeons must often excise excess
      healthy tissue surrounding neoplasms to ensure complete removal of malignant
      tissues. Additional approaches that are commonly used in the detection of tumor
      regions include palpation and conventional ultrasound to locate the affected
      area. However, these techniques suffer from limitations such as minimal
      specificity and lack of depth penetration. Lack of specificity results in the
      production of unclear diseased tissue regions, and therefore fails to offer
      surgeons a reliable and accurate image guidance tool. The proposed work provides
      an alternative diagnostic modality termed ultrasound-stimulated vibro
      acoustography (USVA) that aims to generate detailed images characterized by
      viscoelastic properties of tissues. We demonstrate selective imaging using
      phantom tissue samples of polyvinyl alcohol (PVA) that are altered and arranged
      into unique geometries of varying elastic topology. Determining the precision and
      sensitivity of the USVA imaging system in identifying boundary regions as well as
      intensity ranges associated with tissue phantom targets will provide additional
      important information to allow for a non-invasive tool to distinguish diseased
      tissues from normal tissues in an in vivo setting. 

PMID- 24732518
TI  - Sensor-based assessment of cast placement and removal.
AB  - Appropriate pressure during the application of a cast is critical to provide
      adequate stabilization of fractures. Force-sensing resistors (FSR) were used to
      measure pressure during cast placement and removal. The data demonstrated a
      signature pattern of skin pressure during the different steps of cast placement
      and removal. This reproducible signal provides validity evidence for our model. 

PMID- 24732520
TI  - Touch-free, gesture-based control of medical devices and software based on the
      leap motion controller.
AB  - There are several intra-operative use cases which require the surgeon to interact
      with medical devices. We used the Leap Motion Controller as input device and
      implemented two use-cases: 2D-Interaction (e.g. advancing EPR data) and selection
      of a value (e.g. room illumination brightness). The gesture detection was
      successful and we mapped its output to several devices and systems. 

PMID- 24732521
TI  - Initial biomechanical evaluation of wearable tactile feedback system for gait
      rehabilitation in peripheral neuropathy.
AB  - Peripheral neuropathy (PN) is a significant public health concern, resulting in
      abnormal gait biomechanics, diminished postural stability, and increased risk of
      falls. A wearable tactile feedback system previously developed for sensory
      augmentation of prosthetic limbs has been adapted for individuals with PN and
      evaluated in a pilot group of 4 participants with idiopathic bilateral PN, as
      well as one with Charcot-Marie-Tooth Disease. Participants were assessed both for
      their abilities to perceive tactile stimuli, and for the effect of tactile
      biofeedback on their gait. Preliminary data indicate that most participants could
      localize tactile stimuli and make meaningful modifications to their gait in real
      time, but that the effect of feedback on gait was highly variable from subject to
      subject, demanding further investigation. 

PMID- 24732522
TI  - Virtual reality as allocentric/egocentric technology for the assessment of
      cognitive decline in the elderly.
AB  - Wayfinding ability has a high adaptive value, allowing humans to efficiently
      explore an environment in order to have a goal-oriented activity. This is done
      thanks to the capacity of individuals to actively acquire knowledge during
      interaction. Recently, different studies examined the wayfinding performances of
      older adults in Virtual Reality. While these studies underlined a greater
      difficulty with the wayfinding task in the elderly subjects, the effects of age
      on specific aspects of navigational tasks are less well specified. More, a recent
      study (Konishi & Bohbot, 2013) suggested that older people who use spatial
      navigational strategies (navigation is achieved by orientating oneself in
      relation to an allocentic landmark map) in their everyday lives may have
      increased gray matter in the hippocampus and enhance their probability of healthy
      and successful aging. To evaluate this hypothesis we tested 176 subjects (from 20
      to 89 years old) in wayfinding ability by using an interactive computer-based
      evaluation tool - the VR Maze spatial task - that requires the translation of the
      allocentric spatial knowledge to the corresponding egocentric one and its
      organization to perform a goal directed wayfinding. More, the study explored the
      relationships of these abilites with traditional paper and pencil measures of
      memory, executive and attentive functions. Data show how some aspects of spatial
      ability impairment are not clearly detectable using classical tests, whereas they
      become evident using the VR Maze spatial task. This difference is even more
      marked in the wayfinding ability evaluation of the elderly population. Finally,
      the VR Maze spatial task appears to be correlated with classical
      neuropsychological tests. 

PMID- 24732523
TI  - Particle Based Simulation of the Aortic Valve by Considering Heart's Pulsation.
AB  - We have performed a dynamic simulation of the aortic valve by considering heart's
      pulsation. In the simulation, there are two different types of materials: elastic
      body for the aortic wall and the aortic valve, and fluid for blood. In order to
      calculate the collision detection between two different types of materials, we
      have used a particle method. In addition, the pressure difference between the
      left ventricle and the aorta causes the blood flow in the inside of the aorta.
      Then, the pressure change is given as the parameter of the simulation by
      referring to the typical pattern of the heart's pulsation. Finally, we have
      succeeded in performing the simulation on opening and closing of the aortic
      valve, and have also visualized the pressure in the inside of the aorta and the
      stress distribution on the aortic valve. 

PMID- 24732524
TI  - Portable system for auscultation and lung sound analysis.
AB  - A portable system for auscultation and lung sound analysis has been developed,
      including the original electronic stethoscope coupled with mobile devices and
      special algorithms for the automated analysis of pulmonary sound signals. It's
      planned that the developed system will be used for monitoring of health status of
      patients with various pulmonary diseases. 

PMID- 24732525
TI  - Monte carlo based simulation for evaluating optode fiber placement in prefrontal
      cortex imaging of motor skills during surgical training.
AB  - This study investigates the sensitivity of fiber placement positioning for the
      purpose of prefrontal cortex imaging using functional near-infrared spectroscopy
      (fNIRS). Results indicate that our proposed optode placement has higher scaled
      absorption sensitivity than the traditional International 10-20 system for optode
      placement based on Monte Carlo simulations. 

PMID- 24732526
TI  - Realism, criterion validity, and training capability of simulated diagnostic
      cerebral angiography.
AB  - Computer-based simulation is increasingly used in medical education for training,
      assessment, credentialing, and practice. Compared to medical specialties such as
      anesthesiology and general surgery, the adoption of simulation for
      neurointerventional training has been slow. This may be due to the limited number
      of neurointerventional simulators available and the lack of research assessing
      their validity and training capability. The objective of this study was to assess
      the realism, validity, and training capability of computer-based simulation for
      diagnostic cerebral angiography using a commercially available simulator called
      the ANGIO Mentor Express. 

PMID- 24732527
TI  - A hybrid contact model for cannulation simulation of ERCP.
AB  - This paper proposes a hybrid contact model, which enables an efficient simulation
      of cannulation procedure of ERCP. Meshless model and mass-spring model are
      employed together to construct the major papilla model. This method divides
      contact cases into visible and invisible contacts. We employ Signorini's contact
      model for visible contacts and develop the centerline-based contact model for
      invisible contacts. The comparison in computation time verifies that our proposed
      model reduces computation time up to eighty percent. 

PMID- 24732528
TI  - A method for semi-automatic nuchal translucency thickness measurement.
AB  - Increased nuchal translucency (NT) thickness is associated with major
      abnormalities of the heart, great arteries and a wide range of genetic syndromes.
      NT thickness is one of the most important ultrasound markers in fetal diseases
      screening. To find an applicable method that accurately detects NT, we use an
      algorithm based on modified level set for semi-automated segmentation of the
      region. A regression model is used to find the appropriate direction of NT
      thickness measurement. The results show 4.5% error. 

PMID- 24732529
TI  - Complete Real-Time Liver Model Including Glisson's Capsule, Vascularization and
      Parenchyma.
AB  - Accurate biomechanical modeling of liver is of paramount interest in pre
      operative planning or computer-aided per-operative guidance. Since the liver is
      an organ composed of three different components (parenchyma, vascularization and
      Glisson's capsule), an efficient and realistic simulation of its behaviour is a
      challenging task. In this paper we propose a complete model of liver where each
      component is modelled with different type of finite elements chosen according to
      the nature and mechanical properties of the component. The elements of different
      types are coupled via mechanical mapping encoded in the global stiffness matrix.
      In the result section, we first focus on simulation of Glisson's capsule using
      constant-strain triangular elements: we compare the model to a detailed non-real
      time model and also reproduce previously published aspiration test showing the
      importance of the capsule. Finally, we demonstrate that the proposed complete
      liver model can be used in a real-time simulation. 

PMID- 24732530
TI  - Varying the Speed of Perceived Self-Motion Affects Postural Control during
      Locomotion.
AB  - Virtual reality environments have been used to show the importance of perception
      of self-motion in controlling posture and gait. In this study, the authors used a
      virtual reality environment to investigate whether varying optical flow speed had
      any effect on postural control during locomotion. Healthy young adult
      participants walked under two conditions, with optical flow matching their
      preferred walking speed, and with a randomly varying optic flow speed compared to
      their preferred walking speed. Exposure to the varying optic flow increased the
      variability in their postural control as measured by area of COP when compared
      with the matched speed condition. If perception of self-motion becomes less
      predictable, postural control during locomotion becomes more variable and
      possibly riskier. 

PMID- 24732531
TI  - Visualization of Tissue Removal using Focus + Context Techniques.
AB  - Current dataset visualizations have limited capability of allowing users to
      remove only small regions of the dataset and inspect the remaining volume. We
      have developed a new visualization based on the focus + context paradigm to
      provide users with a 3D volume or 2D slice rendering of regions that are marked
      as arbitrary-shaped focus and shown as drilled-out. A novel way of computing
      whether the rays traversing the dataset fall within the drilled-out region
      results in an accurate rendering of the sculpted context dataset. A user study
      showed that the new visualization improves accuracy and speed in tissue removal
      tasks. 

PMID- 24732532
TI  - Expansion of a VR Exposure Therapy System for Combat-Related PTSD to
      Medics/Corpsman and Persons Following Military Sexual Trauma.
AB  - The stressful experiences that have been characteristic of the combat
      environments in Iraq and Afghanistan have produced significant numbers of
      returning service members at risk for developing posttraumatic stress disorder
      and other psychosocial/behavioral health conditions. This paper describes a set
      of projects that are expanding the content for inclusion in a newly updated
      "Virtual Iraq/Afghanistan" Virtual Reality system for the delivery of exposure
      therapy (VRET) for PTSD with Service Members and Veterans. In addition to the
      complete rebuilding of this VRET system using the latest version of the Unity
      Game Engine, the system's content and functionality has been expanded to now
      support the use of VRET with combat medics/corpsmen and persons who have
      experienced military sexual trauma (MST). The focus of this paper is to present
      the rationale and general overview of the progress on these projects that will
      provide new relevant and customizable options for conducting VRET with a wider
      range of trauma experiences. 

PMID- 24732533
TI  - Kinematic Measures for Evaluating Surgical Skills in Natural Orifice Translumenal
      Endoscopic Surgery (NOTES).
AB  - Natural Orifice Translumenal Endoscopic Surgery is an emerging procedure that
      requires training and adoption to be successful. Currently no objective
      performance metrics exist for evaluating skills for NOTES. In this work, we have
      improved upon our previous study on objective performance metrics using kinematic
      measures by introducing two new measures, the flex and the roll and recruiting
      more subjects to increase the statistical power. The measures were evaluated in a
      transgastric NOTES appendectomy procedure performed with ex-vivo organs using the
      EASIE-R<sup>TM</sup> trainer box. Four motion tracking sensors attached to an
      endoscope were used to measure the scope position and orientation to compute the
      kinematic measures. Results from our study showed that completion time, economy
      of motion, jerk and roll of the scope are valid kinematic measures to
      differentiate between expert and novice NOTES surgeons. 

PMID- 24732534
TI  - The effect of contextual sound cues on visual fidelity perception.
AB  - Previous work has shown that sound can affect the perception of visual fidelity.
      Here we build upon this previous work by examining the effect of contextual sound
      cues (i.e., sounds that are related to the visuals) on visual fidelity
      perception. Results suggest that contextual sound cues do influence visual
      fidelity perception and, more specifically, our perception of visual fidelity
      increases with contextual sound cues. These results have implications for
      designers of multimodal virtual worlds and serious games that, with the
      appropriate use of contextual sounds, can reduce visual rendering requirements
      without a corresponding decrease in the perception of visual fidelity. 

PMID- 24732535
TI  - The impact of secondary-task type on the sensitivity of reaction-time based
      measurement of cognitive load for novices learning surgical skills using
      simulation.
AB  - Interest in the measurement of cognitive load (CL) in simulation-based education
      has grown in recent years. In this paper we present two pilot experiments
      comparing the sensitivity of two reaction time based secondary task measures of
      CL. The results suggest that simple reaction time measures are sensitive enough
      to detect changes in CL experienced by novice learners in the initial stages of
      simulation-based surgical skills training. 

PMID- 24732536
TI  - Development of a patient-specific surgical simulator for pediatric laparoscopic
      procedures.
AB  - The purpose of this study is to develop and evaluate a pediatric patient-specific
      surgical simulator for the planning, practice, and validation of laparoscopic
      surgical procedures prior to intervention, initially focusing on the choledochal
      cyst resection and reconstruction scenario. The simulator is comprised of
      software elements including a deformable body physics engine, virtual surgical
      tools, and abdominal organs. Hardware components such as haptics-enabled hand
      controllers and a representative endoscopic tool have also been integrated. The
      prototype is able to perform a number of surgical tasks and further development
      work is under way to simulate the complete procedure with acceptable fidelity and
      accuracy. 

PMID- 24732537
TI  - Haptic device in endoscopy.
AB  - Access to organs and tissues is limited during endoscopy. Information about
      mechanical properties of tissues received during an operation is a key factor for
      deciding the scale of surgery and further treatment strategy. A new device
      developed at Lomonosov Moscow State University determines the visco-elastic
      properties of tissues and presents them in a digital form as a visual image and a
      tactile sense for the surgeon. This data lets users define pathological change of
      tissues and if necessary change treatment policy. 

PMID- 24732538
TI  - A framework for providing cognitive feedback in surgical simulators.
AB  - Providing cognitive feedback in a virtual reality simulator during training is
      essential for subjects to correct and learn proper techniques. In this work, we
      have developed a framework to identify key skills and cognitive knowledge
      required to perform a task and methods to provide to the user. The framework was
      verified by implementing a test case scenario with the peg transfer task of the
      FLS. 

PMID- 24732539
TI  - Cardiovascular blood flow analysis under normal and open injury conditions.
AB  - The aim of this paper is to enable a simulation tool for cardiovascular blood
      flow in order to better understand normal and hemorrhage conditions. A second
      order partial differential model for cardiovascular blood flow is employed. The
      individual components of the model is represented as an RLC circuit
      representation. Injury behavior is simulated by varying the circuit system
      parameters for the section representing different arterial levels. Our results
      show that significant changes in the blood flow inside the cardiovascular system
      can be observed when different injury conditions are modeled. 

PMID- 24732540
TI  - A framework for modeling and visualizing cardiovascular deformation under normal
      and altered circulatory conditions.
AB  - The aim of this paper is to model and visualize cardiovascular deformations in
      order to better understand vascular movements inside the lung and heart caused by
      abnormal cardiac conditions. The modeling was performed in two steps: first step
      involved modeling the cardiac output taking into account of the heart rate and
      preload blood volume, contractility and systematic vascular resistance. The
      second step involved deforming a 3D cine cardiac gated Magnetic Resonance Volume
      to the corresponding cardiac output. Cardiac-gated MR imaging of 4 healthy
      volunteers were acquired. For each volunteer, a total of 24 short-axis and 18
      radial planar views were acquired on a 1.5 T MR scanner during a series of 12-15
      second breath-hold maneuvers. A 3D multi-resolution optical flow deformable image
      registration algorithm was used to quantify the volumetric cardiovascular
      displacements for known cardiac outputs. Results show that a real-time
      visualization of the vascular deformations inside both the lung as well as the
      heart can be seen for different cardiac outputs representing normal and abnormal
      cardiac conditions. 

PMID- 24732541
TI  - Endovascular seldinger needle placement: a simulator for examining haptic skills.
AB  - In this work, we develop an affordable haptic simulator for examining haptic
      skills required for endovascular Seldinger needle placement. 

PMID- 24732542
TI  - Anatomic surface reconstruction from sampled point cloud data and prior models.
AB  - In this paper, we propose an approach for reconstruction of an anatomic surface
      model from point cloud data using the Screened Poisson Surface Reconstruction
      algorithm, which requires a collection of points and their normal vectors.
      Various algorithms exist for estimating normal vectors for point cloud data;
      however, in this work we describe a novel approach to estimating the normal
      vectors from a high-resolution prior model. In many medical applications, a
      preoperative high-resolution scan is acquired for diagnostic and planning
      purposes, whereas intraoperative, lower fidelity imaging is utilized during the
      procedure. This approach assumes an already existing registration between intra
      operatively acquired data and the preoperative model. We conducted simulation
      experiments to evaluate the effect of registration error, point sampling rate,
      and noise levels on the acquired point cloud data samples. In addition, we
      evaluated the effect of using both the closest point, as well as a neighborhood
      of closest points on the prior model for estimating the normal. Our results
      showed that surface reconstruction error increases with higher registration
      error; however, acceptable performance was achieved with clinically-acceptable
      registration error. In addition, the best reconstruction was obtained when
      estimating the normal using only the closest point on the prior model, as opposed
      to utilizing a neighborhood of points. When combining the effect of all factors
      (Gaussian sampling noise of zero mean and sigma=1.8mm; Gaussian translational
      error of zero mean and sigma=2.0mm; and Gaussian rotational error of zero mean
      and sigma=3 degrees ) the overall RMS reconstruction error was 0.88+/-0.03mm. 

PMID- 24732543
TI  - The medical simulation markup language - simplifying the biomechanical modeling
      workflow.
AB  - Modeling and simulation of the human body by means of continuum mechanics has
      become an important tool in diagnostics, computer-assisted interventions and
      training. This modeling approach seeks to construct patient-specific
      biomechanical models from tomographic data. Usually many different tools such as
      segmentation and meshing algorithms are involved in this workflow. In this paper
      we present a generalized and flexible description for biomechanical models. The
      unique feature of the new modeling language is that it not only describes the
      final biomechanical simulation, but also the workflow how the biomechanical model
      is constructed from tomographic data. In this way, the MSML can act as a
      middleware between all tools used in the modeling pipeline. The MSML thus greatly
      facilitates the prototyping of medical simulation workflows for clinical and
      research purposes. In this paper, we not only detail the XML-based modeling
      scheme, but also present a concrete implementation. Different examples highlight
      the flexibility, robustness and ease-of-use of the approach. 

PMID- 24732544
TI  - Towards open-source, low-cost haptics for surgery simulation.
AB  - In minimally invasive surgery (MIS), virtual reality (VR) training systems have
      become a promising education tool. However, the adoption of these systems in
      research and clinical settings is still limited by the high costs of dedicated
      haptics hardware for MIS. In this paper, we present ongoing research towards an
      open-source, low-cost haptic interface for MIS simulation. We demonstrate the
      basic mechanical design of the device, the sensor setup as well as its software
      integration. 

PMID- 24732545
TI  - Development of AR Surgical Navigation Systems for Multiple Surgical Regions.
AB  - The purpose of our research is to develop surgical navigation systems to enhance
      surgical safety. Our systems make use of augmented reality technology to
      superimpose, on the surgery screen on a real time basis, patients' organ models
      reconstructed in 3D from their X-ray CT data taken before surgery. By doing so,
      the systems display anatomical risk materials, tumors and blood vessels which
      surgeons cannot see with their naked eyes. This will in turn lead to surgeons
      intuitively grasping the inner structures of the operational fields. We so far
      have been developing navigation systems that can conduct surgeries in various
      fields. The basic structure of the navigation systems are the same. The
      navigation systems uses different peripheral equipment and different methods to
      display navigation images which best meet the demands of each type of surgery. In
      this thesis, we report on our navigation systems for 2 types of surgery -
      endoscopic sinus surgery and hepatobilialy-pancreatic surgery. 

PMID- 24732546
TI  - A concept for overlaid-type surgical navigation system with organ modification
      functions using non-contact type surface measurement.
AB  - Surgical navigation systems are clinically applied in cerebral and otological
      surgeries but they are only used in parts with minimum surgical transformation in
      regions in which the organs largely transform, such as in the abdomen. Therefore,
      we here propose a concept of a surgical navigation system that could be used in
      the regions such as liver, which largely transforms itself during surgery. We
      consider a method that measures the changes in the organ surface configuration
      during surgery and estimates the changes in the tumor and blood vessel structure
      following the transformation of the organ surface. We also report on the
      necessary disposition of each process of this method, especially on the basic
      examination of the organ transformation. 

PMID- 24732547
TI  - Sensing and visualization tools for objective assessment and debriefing of high
      risk neonatal resuscitation training scenarios.
AB  - We present TeamVis, a set of tools for sensing and visualization of objective
      team performance in a simulated medical scenario. TeamVis helps teams,
      instructors, and researchers in observation, analysis, and evaluation of team
      behavior. The current system supports analysis of team movements and verbal
      communication. The system has potential to provide deeper insight into team
      performance, enabling design of more effective simulation training scenarios.
      Furthermore, the observed metrics can aid trainee debriefings by providing
      another mechanism for learning through self-reflection. 

PMID- 24732548
TI  - Interactive planning of cryotherapy using physics-based simulation.
AB  - Cryotherapy is a rapidly growing minimally invasive technique for the treatment
      of certain tumors. It consists in destroying cancer cells by extreme cold
      delivered at the tip of a needle-like probe. As the resulting iceball is often
      smaller than the targeted tumor, a key to the success of cryotherapy is the
      planning of the position and orientation of the multiple probes required to treat
      a tumor, while avoiding any damage to the surrounding tissues. In order to
      provide such a planning tool, a number of challenges need to be addressed such as
      fast and accurate computation of the freezing process or interactive positioning
      of the virtual cryoprobes in the pre-operative image volume. To address these
      challenges, we present an approach which relies on an advanced computational
      framework, and a gesture-based planning system using contact-less technology to
      remain compatible with a use in a sterile environment. 

PMID- 24732549
TI  - Liver biomechanical model for virtual palpation.
AB  - Palpation is a diagnostic technique used for evaluating physical properties of
      abdominal tissues and organs. The emulation of this procedure using virtual
      simulators is challenging due to trades between realism and interactivity. In
      this paper a virtual palpation system of the liver is proposed using a polyhedral
      mesh with a first order viscoelastic model defined in terms of its biomechanical
      properties extracted from experimental data. The hepatic tissue model is
      approximated to large deformations leading to a realistic haptic response of the
      procedure. 

PMID- 24732550
TI  - Development of a tele-anesthesia preoperative clinic to support distant military
      treatment facilities for the European regional medical command.
AB  - Landstuhl Regional Medical Center (LRMC) provides primary care services for more
      than 65,000 beneficiaries and specialty care and hospitalization for 245,000 U.S.
      Service Members and their Families serving in Europe. These personnel are located
      in Germany, Italy and Belgium (See Fig 1). Anesthesia preoperative diagnosis/work
      was done by telemedicine at the distant, end user site, and significant cost
      savings and enhanced patient service was accomplished. A novel use of existing
      technologies was implemented to enhance provider and patient satisfaction and
      create a sustainable, user friendly system. 

PMID- 24732551
TI  - Real-time simulation of transesophageal echocardiography.
AB  - In this paper we describe an approach to interactively render ultrasound images
      for a transesophageal echocardiogram procedure. Our prototype features an
      animated 3D model of a human heart that is used to synthesize virtual ultrasound
      images in real-time. The user can control the probe and interact with the
      simulator via a GUI or with a haptics device. The ultrasound plane is rendered in
      a classical 2D view but can also be displayed in the context of the 3D heart
      model. 

PMID- 24732552
TI  - Design and Validation of 3D Printed Complex Bone Models with Internal Anatomic
      Fidelity for Surgical Training and Rehearsal.
AB  - Physical models of complex bony structures can be used for surgical skills
      training. Current models focus on surface rendering but suffer from a lack of
      internal accuracy due to limitations in the manufacturing process. We describe a
      technique for generating internally accurate rapid-prototyped anatomical models
      with solid and hollow structures from clinical and microCT data using a 3D
      printer. In a face validation experiment, otolaryngology residents drilled a
      cadaveric bone and its corresponding printed model. The printed bone models were
      deemed highly realistic representations across all measured parameters and the
      educational value of the models was strongly appreciated. 

PMID- 24732553
TI  - Anthropomorphic passive mechanism for performing hand exercises.
AB  - Hand disabilities resulting from traumas, accidents and other causes impact how
      people carry on everyday tasks, thus, the importance of physical therapy. This
      process is characterized for performing repetitive sequences of motion with the
      guidance of a physical therapist, and in some cases, requires doing the therapy
      without attendance, which may lead to unsatisfactory results due to pain, unclear
      guides and poor feedback on their performance. This paper presents the
      development of a humanoid passive mechanism for hand exercising using its limbs
      for achieving flexion/extension, pronation/supination and radial/ulnar
      deviations. Preliminary tests show an interest in having similar devices for hand
      training associated as a leisure activity that could be used as a stress reliever
      that allows entertaining while training. 

PMID- 24732554
TI  - Human eye haptics-based multimedia.
AB  - Immersive and interactive multimedia applications offer complementary study tools
      in anatomy as users can explore 3D models while obtaining information about the
      organ, tissue or part being explored. Haptics increases the sense of interaction
      with virtual objects improving user experience in a more realistic manner. Common
      eye studying tools are books, illustrations, assembly models, and more recently
      these are being complemented with mobile apps whose 3D capabilities, computing
      power and customers are increasing. The goal of this project is to develop a
      complementary eye anatomy and pathology study tool using deformable models within
      a multimedia application, offering the students the opportunity for exploring the
      eye from up close and within with relevant information. Validation of the tool
      provided feedback on the potential of the development, along with suggestions on
      improving haptic feedback and navigation. 

PMID- 24732555
TI  - Toward a realistic simulation of organ dissection.
AB  - Whilst laparoscopic surgical simulators are becoming increasingly realistic they
      can not, as yet, fully replicate the experience of live surgery. In particular
      tissue dissection in one task that is particularly challenging to replicate.
      Limitation of current attempts to simulate tissue dissection include: poor visual
      rendering; over simplification of the task and; unrealistic tissue properties. In
      an effort to generate a more realistic model of tissue dissection in laparoscopic
      surgery we propose a novel method based on task analysis. Initially we have
      chosen to model only the basic geometrics of this task rather than a whole
      laparoscopic procedure. Preliminary work has led to the development of a real
      time simulator performing organ dissection with a haptic thread at 1000Hz. A
      virtual cutting tool, manipulated through a haptic device, in combination with 1D
      and 2D soft-tissue models
      accuratelyreplicatetheprocessoflaparoscopictissuedissection. 

PMID- 24732556
TI  - Tourniquet Master Training for Junctional and Inguinal Hemorrhage Control (TMT).
AB  - Junctional and inguinal bleeding is a significant and challenging problem on the
      battlefield. Inventors have developed new types of tourniquets, including the
      Abdominal Aortic TourniquetTM (AAT) and the Combat Ready ClampTM (CRoC) to
      address these abdominal and pelvic injuries. While these hemorrhage control
      technologies have been developed, validated, and approved for use, training
      systems that teach and refresh skills related to these technologies have not been
      developed. These training systems are vital because these skills can be difficult
      to train and are infrequently used. To address these needs, a sensor-enabled
      manikin was designed. Using the sensor data, the different phases of applying the
      tourniquet were captured and key performance was measured. 

PMID- 24732557
TI  - A temporal bone surgery simulator with real-time feedback for surgical training.
AB  - Timely feedback on surgical technique is an important aspect of surgical skill
      training in any learning environment, be it virtual or otherwise. Feedback on
      technique should be provided in real-time to allow trainees to recognize and
      amend their errors as they occur. Expert surgeons have typically carried out this
      task, but they have limited time available to spend with trainees. Virtual
      reality surgical simulators offer effective, repeatable training at relatively
      low cost, but their benefits may not be fully realized while they still require
      the presence of experts to provide feedback. We attempt to overcome this
      limitation by introducing a real-time feedback system for surgical technique
      within a temporal bone surgical simulator. Our evaluation study shows that this
      feedback system performs exceptionally well with respect to accuracy and
      effectiveness. 

PMID- 24732558
TI  - Real-time haptic cutting of high-resolution soft tissues.
AB  - We present our systematic efforts in advancing the computational performance of
      physically accurate soft tissue cutting simulation, which is at the core of
      surgery simulators in general. We demonstrate a real-time performance of 15
      simulation frames per second for haptic soft tissue cutting of a deformable body
      at an effective resolution of 170,000 finite elements. This is achieved by the
      following innovative components: (1) a linked octree discretization of the
      deformable body, which allows for fast and robust topological modifications of
      the simulation domain, (2) a composite finite element formulation, which
      thoroughly reduces the number of simulation degrees of freedom and thus enables
      to carefully balance simulation performance and accuracy, (3) a highly efficient
      geometric multigrid solver for solving the linear systems of equations arising
      from implicit time integration, (4) an efficient collision detection algorithm
      that effectively exploits the composition structure, and (5) a stable haptic
      rendering algorithm for computing the feedback forces. Considering that our
      method increases the finite element resolution for physically accurate real-time
      soft tissue cutting simulation by an order of magnitude, our technique has a high
      potential to significantly advance the realism of surgery simulators. 

PMID- 24732559
TI  - Smart Dry Lab: An Augmented Reality (AR) Based Surgical Training Box.
AB  - Smart Dry Lab (SDL) is a low-cost, AR-based surgical training box, using the
      ARToolKit API. This is an add-on function for existing surgical training box,
      which enables quantitative evaluation of forceps maneuver and simulation of soft
      tissue deformation. In this paper we demonstrate functionality of our prototype
      system. 

PMID- 24732560
TI  - An immersive surgery training system with live streaming capability.
AB  - Providing real-time, interactive immersive surgical training has been a key
      research area in telemedicine. Earlier approaches have mainly adopted videotaped
      training that can only show imagery from a fixed view point. Recent advances on
      commodity 3D imaging have enabled a new paradigm for immersive surgical training
      by acquiring nearly complete 3D reconstructions of actual surgical procedures.
      However, unlike 2D videotaping that can easily stream data in real-time, by far
      3D imaging based solutions require pre-capturing and processing the data;
      surgical trainings using the data have to be conducted offline after the
      acquisition. In this paper, we present a new real-time immersive 3D surgical
      training system. Our solution builds upon the recent multi-Kinect based surgical
      training system [1] that can acquire and display high delity 3D surgical
      procedures using only a small number of Microsoft Kinect sensors. We build on top
      of the system a client-server model for real-time streaming. On the server front,
      we efficiently fuse multiple Kinect data acquired from different viewpoints and
      compress and then stream the data to the client. On the client front, we build an
      interactive space-time navigator to allow remote users (e.g., trainees) to
      witness the surgical procedure in real-time as if they were present in the room. 

PMID- 24732564
TI  - Acute coagulopathy in pediatric trauma.
AB  - PURPOSE OF REVIEW: To summarize our current understanding of the pathophysiology,
      diagnosis, and management of acute traumatic coagulopathy in children. RECENT
      FINDINGS: Traumatic coagulopathy is a complex process that leads to global
      dysfunction of the endogenous coagulation system and results in worse outcomes
      and increased mortality. Although the cause is multifactorial, it is common in
      severely injured patients and is driven by significant tissue injury and
      hypoperfusion. Viscoelastic coagulation tests have been established as a rapid
      and reliable method to assess traumatic coagulopathy. Additionally, massive
      transfusion protocols have improved outcomes in adults, but limited studies in
      pediatrics have not shown any difference in mortality. SUMMARY: Prospective
      studies are needed to determine how to best diagnose and manage acute traumatic
      coagulopathy in children.

PMID- 24732565
TI  - Pediatric lung transplantation: promise being realized.
AB  - PURPOSE OF REVIEW: Lung transplantation for infants and children is an accepted
      but rarely exercised option for the treatment of end-stage lung disease, with
      outcomes equivalent to those for adults. However, widespread misconceptions
      regarding pediatric outcomes often confound timely and appropriate referral to
      specialty centers. We present the updated information for primary pediatricians
      to utilize when counseling families with children confronted by progressive end
      stage pulmonary or cardiovascular disease. RECENT FINDINGS: We provide general
      guidelines to consider for referral, and discuss allocation of organs in
      children, information regarding standard treatment protocols, and survival
      outcomes. SUMMARY: Lung transplantation is a worthwhile treatment option to
      consider in children with end-stage lung disease. The treatment is complex, but
      lung transplant provides substantial survival benefit and markedly improved
      quality of life for children and their families. This timely review provides
      comprehensive information for pediatricians who are considering options for
      treatment of children with end-stage lung disease.

PMID- 24732567
TI  - The time course of top-down control on saccade averaging.
AB  - When objects in a visual scene are positioned in close proximity, eye movements
      to these objects tend to land at an intermediate location between the objects
      (i.e., the global effect). This effect is most pronounced for short latency
      saccades and is therefore believed to be reflexive and dominantly controlled by
      bottom-up information. At longer latencies this effect can be modulated by top
      down factors. The current study established the time course at which top-down
      information starts to have an influence on bottom-up averaging. In a standard
      global effect task two peripheral stimuli (a red and a green abrupt onset) were
      positioned within an angular distance of 20 degrees . In the condition in which
      observers received no specific target instruction, the eyes landed in between the
      red and green element establishing the classic global effect. However, when
      observers were instructed to make a saccade to the red element during a whole
      block or when the target color varied from trial-to-trial (red or green), a clear
      effect of the target instruction on the accuracy of the landing position of the
      primary saccade was found. With increasing saccade latencies, the eyes landed
      closer to the instructed target. Crucially, however, this effect was even seen
      for the shortest saccade latencies (as early as 200 ms), suggesting that saccade
      averaging is affected early on by top-down processes.

PMID- 24732566
TI  - Venous thromboembolism in critically ill children.
AB  - PURPOSE OF REVIEW: To review the current literature on venous thromboembolism
      (VTE) in critically ill children. RECENT FINDINGS: There is an increasing concern
      for VTE and its complications in critically ill children. Critically ill children
      are at increased risk of thromboembolism because of the treatment that they are
      receiving and their underlying condition. A complex relationship exists between
      thrombosis and infection. A thrombus is a nidus for infection, while infection
      increases the risk of thrombosis. Pediatric-specific guidelines for the
      prevention and treatment of thromboembolism are lacking. Current guidelines are
      based on the data from adults. Novel anticoagulants are now available for use in
      adults. Studies are ongoing to determine their safety in children. Risk
      assessment tools have recently been developed to determine the risk of
      thromboembolism in critically ill children. Certain molecules are associated with
      thromboembolism in adults. SUMMARY: Pediatric critical care practitioners should
      be cognizant of the importance of VTE in critically ill children to allow early
      identification and treatment. Adequately powered clinical trials are critically
      needed to generate evidence that will guide the treatment and prevention of
      thromboembolism in critically ill children. Risk assessment tools that
      incorporate biomarkers may improve our ability to predict the occurrence of
      thromboembolism in critically ill children.

PMID- 24732568
TI  - Development of sampling efficiency and internal noise in motion detection and
      discrimination in school-aged children.
AB  - The aim of this study was to use an equivalent noise paradigm to investigate the
      development and maturation of motion perception, and how the underlying
      limitations of sampling efficiency and internal noise effect motion detection and
      direction discrimination in school-aged children (5-14 years) and adults.
      Contrast energy thresholds of a 2c/deg sinusoidal grating drifting at 1.0 or 6.0
      Hz were measured as a function of added dynamic noise in three tasks: detection
      of a drifting grating; detection of the sum of two oppositely drifting gratings
      and direction discrimination of oppositely drifting gratings. Compared to the
      ideal observer, in both children and adults, the performance for all tasks was
      limited by reduced sampling efficiency and internal noise. However, the
      thresholds for discrimination of motion direction and detection of moving
      gratings show very different developmental profiles. Motion direction
      discrimination continues to improve after the age of 14 years due to an increase
      in sampling efficiency that differs with speed. Motion detection and summation
      were already mature at the age of 5 years, and internal noise was the same for
      all tasks. These findings were confirmed in a 1-year follow-up study on a group
      of children from the initial study. The results support suggestions that the
      detection of a moving pattern and discriminating motion direction are processed
      by different systems that may develop at different rates.

PMID- 24732570
TI  - Effects of fluoroquinolone eye solutions without preservatives on human corneal
      epithelial cells in vitro.
AB  - AIMS: To evaluate the biologic effects of fluoroquinolone eye solutions without
      preservatives on cultured human corneal epithelial cells in vitro. METHODS: We
      studied the effect of diverse generations of topical fluoroquinolones such as
      ofloxacin 0.3%, levofloxacin 0.5%, tosufloxacin 0.3%, moxifloxacin 0.5% and
      gatifloxacin 0.3% on cultured human corneal epithelial cells. MTT-based
      calorimetric assay, lactate dehydrogenase leakage (LDH) assay and scratch wound
      test were performed. Corneal epithelial cell morphologies were examined by
      performing inverted light microscopy and transmission electron microscopy.
      RESULTS: In all topical fluoroquinolones, the metabolic activity of the corneal
      epithelial cells decreased in a time-dependent fashion and the LDH titer
      increased with longer exposure times. Especially, the LDH titers significantly
      increased after exposure to moxifloxacin 0.5% and gatifloxacin 0.3% compared with
      controls. The migration rates of the corneal epithelial cells were faster in
      ofloxacin 0.3% or levofloxacin 0.5% than other fluoroquinolones. Severe cellular
      morphological damage was observed after exposure to moxifloxacin 0.5% and
      gatifloxacin 0.3%. CONCLUSIONS: As moxifloxacin 0.5% and gatifloxacin 0.3%
      induced the toxic effect to the corneal epithelial cells, compared with other
      fluoroquinolones, the 4th fluoroquinolone eye solutions should be carefully used
      in case of the corneal epithelium is damaged by long duration of treatment or
      overdosage.

PMID- 24732571
TI  - Understanding consumer evaluations of personalised nutrition services in terms of
      the privacy calculus: a qualitative study.
AB  - BACKGROUND: Personalised nutrition (PN) may provide major health benefits to
      consumers. A potential barrier to the uptake of PN is consumers' reluctance to
      disclose sensitive information upon which PN is based. This study adopts the
      privacy calculus to explore how PN service attributes contribute to consumers'
      privacy risk and personalisation benefit perceptions. METHODS: Sixteen focus
      groups (n = 124) were held in 8 EU countries and discussed 9 PN services that
      differed in terms of personal information, communication channel, service
      provider, advice justification, scope, frequency, and customer lock-in.
      Transcripts were content analysed. RESULTS: The personal information that
      underpinned PN contributed to both privacy risk perception and personalisation
      benefit perception. Disclosing information face-to-face mitigated the perception
      of privacy risk and amplified the perception of personalisation benefit. PN
      provided by a qualified expert and justified by scientific evidence increased
      participants' value perception. Enhancing convenience, offering regular face-to
      face support, and employing customer lock-in strategies were perceived as
      beneficial. CONCLUSION: This study suggests that to encourage consumer adoption,
      PN has to account for face-to-face communication, expert advice providers,
      support, a lifestyle-change focus, and customised offers. The results provide an
      initial insight into service attributes that influence consumer adoption of PN.

PMID- 24732569
TI  - Development of a radioiodinated triazolopyrimidine probe for nuclear medical
      imaging of fatty acid binding protein 4.
AB  - Fatty acid binding protein 4 (FABP4) is the most well-characterized FABP isoform.
      FABP4 regulates inflammatory pathways in adipocytes and macrophages and is
      involved in both inflammatory diseases and tumor formation. FABP4 expression was
      recently reported for glioblastoma, where it may participate in disease
      malignancy. While FABP4 is a potential molecular imaging target, with the
      exception of a tritium labeled probe there are no reports of other nuclear
      imaging probes that target this protein. Here we designed and synthesized a
      nuclear imaging probe, [123I]TAP1, and evaluated its potential as a FABP4
      targeting probe in in vitro and in vivo assays. We focused on the unique
      structure of a triazolopyrimidine scaffold that lacks a carboxylic acid to design
      the TAP1 probe that can undergo facilitated delivery across cell membranes. The
      affinity of synthesized TAP1 was measured using FABP4 and 8-anilino-1-naphthalene
      sulfonic acid. [125I]TAP1 was synthesized by iododestannylation of a precursor,
      followed by affinity and selectivity measurements using immobilized FABPs.
      Biodistributions in normal and C6 glioblastoma-bearing mice were evaluated, and
      excised tumors were subjected to autoradiography and immunohistochemistry. TAP1
      and [125I]TAP1 showed high affinity for FABP4 (Ki = 44.5+/-9.8 nM, Kd = 69.1+/
      12.3 nM). The FABP4 binding affinity of [125I]TAP1 was 11.5- and 35.5-fold higher
      than for FABP3 and FABP5, respectively. In an in vivo study [125I]TAP1 displayed
      high stability against deiodination and degradation, and moderate radioactivity
      accumulation in C6 tumors (1.37+/-0.24% dose/g 3 hr after injection). The
      radioactivity distribution profile in tumors partially corresponded to the FABP4
      positive area and was also affected by perfusion. The results indicate that
      [125I]TAP1 could detect FABP4 in vitro and partly in vivo. As such, [125I]TAP1 is
      a promising lead compound for further refinement for use in in vivo FABP4
      imaging. 

PMID- 24732572
TI  - Advantages and limitations of anticipating laboratory test results from
      regression- and tree-based rules derived from electronic health-record data.
AB  - Laboratory testing is the single highest-volume medical activity, making it
      useful to ask how well one can anticipate whether a given test result will be
      high, low, or within the reference interval ("normal"). We analyzed 10 years of
      electronic health records--a total of 69.4 million blood tests--to see how well
      standard rule-mining techniques can anticipate test results based on patient age
      and gender, recent diagnoses, and recent laboratory test results. We evaluated
      rules according to their positive and negative predictive value (PPV and NPV) and
      area under the receiver-operator characteristic curve (ROC AUCs). Using a
      stringent cutoff of PPV and/or NPV>=0.95, standard techniques yield few rules for
      sendout tests but several for in-house tests, mostly for repeat laboratory tests
      that are part of the complete blood count and basic metabolic panel. Most rules
      were clinically and pathophysiologically plausible, and several seemed clinically
      useful for informing pre-test probability of a given result. But overall, rules
      were unlikely to be able to function as a general substitute for actually
      ordering a test. Improving laboratory utilization will likely require different
      input data and/or alternative methods.

PMID- 24732573
TI  - Increased arterial stiffness in inflammatory bowel diseases is dependent upon
      inflammation and reduced by immunomodulatory drugs.
AB  - BACKGROUND: Inflammatory bowel diseases (IBD) are associated with an increased
      cardiovascular risk that is not fully explained by traditional cardiovascular
      risk factors but may be due to inflammation and mediated by an increased arterial
      stiffness. AIMS: Study 1, to investigate the relationship between inflammation
      and arterial stiffening; Study 2, to look whether aortic stiffening is reduced by
      immunomodulatory therapy in IBD. METHODS: Study 1 (Cross-sectional study): pulse
      wave velocity (PWV) was measured in 74 IBD subjects (40 ulcerative colitis and 34
      Crohn's disease) and 80 matched controls. Study 2 (Longitudinal study): the
      effect of therapy on PWV was measured at baseline and 3.4 +/- 0.5 years later in
      14 IBD subjects treated only with salicylates, 11 subjects treated with steroids
      and azathioprine, 7 subjects treated with anti TNF-alpha and 30 matched controls.
      RESULTS: Study 1: All parameters were comparable between subjects with ulcerative
      colitis and Crohn's disease. Compared to controls, subjects with ulcerative
      colitis and those with Crohn's disease have both higher carotid-femoral PWV (7.0
      +/- 1.1, 7.8 +/- 1.7 and 8.0 +/- 1.6 m/s, respectively; P < 0.001) and carotid
      radial PWV (7.2 +/- 0.9, 8.8 +/- 1.4 and 8.8 +/- 1.3 m/s, respectively; P <
      0.001). In fully adjusted models carotid-femoral PWV was positively associated
      with disease duration whereas carotid-radial PWV was associated with C-reactive
      protein and history of relapse. Study 2: in fully adjusted model carotid-femoral
      PWV increased significantly at follow-up in IBD subjects treated with salicylates
      but not in those treated with steroids and azathioprine or anti TNF-alpha.
      CONCLUSION: Increased arterial stiffness in IBD is dependent upon inflammation
      and reduced by immunomodulatory drugs.

PMID- 24732574
TI  - Activated platelets promote increased monocyte expression of CXCR5 through
      prostaglandin E2-related mechanisms and enhance the anti-inflammatory effects of
      CXCL13.
AB  - BACKGROUND: We have previously shown that the homeostatic chemokine CXCL13 is up
      regulated in monocytes in atherosclerosis, mediating anti-apoptotic and anti
      inflammatory effects. OBJECTIVE: To investigate the regulation of CXCL13s
      receptor, CXCR5. METHODS/PATIENTS: In vitro studies in THP-1 and primary
      monocytes and studies of CXCR5 expression in thrombus material obtained at the
      site of plaque rupture during myocardial infarction (MI). RESULTS: Our major
      findings were: (i) toll-like receptor agonists and particularly beta-adrenergic
      receptor activation and releasate from thrombin-activated platelets increased
      CXCR5 mRNA levels in monocytes. (ii) The platelet-mediated induction of CXCR5
      involved prostaglandin E2/cAMP/protein kinase A-dependent as well as RANTES
      dependent pathways with NFkappaB activation as a potential common down-stream
      mediator. (iii) Releasate from thrombin-activated platelets augmented the anti
      inflammatory effects of CXCL13 in monocytes at least partly by enhancing the
      effects of CXCL13 on CXCR5 expression. (iv) We found strong immunostaining of
      CXCR5 in thrombus material obtained at the site of plaque rupture in patients
      with ST elevation MI (STEMI) and in unstable carotid lesions, co-localized with
      platelets. CONCLUSION: Our findings suggest that platelet-mediated signaling
      through CXCR5 may be active in vivo during plaque destabilization, potentially
      representing a counteracting mechanism to inflammation.

PMID- 24732575
TI  - Association of borderline ankle-brachial index with mortality and the incidence
      of peripheral artery disease in diabetic patients.
AB  - OBJECTIVE: Peripheral artery disease (PAD) and diabetes mellitus are significant
      risk factors for all-cause death or cardiovascular death. PAD occurs more
      frequently in diabetic than in non-diabetic patients. However, the association of
      ankle-brachial index (ABI), especially borderline ABI, with clinical outcomes has
      not been fully elucidated in diabetic patients. This study aimed to investigate
      the association of ABI with mortality and the incidence of PAD in Japanese
      diabetic patients. METHODS: This observational study included 3981 diabetic
      patients (61.0 +/- 11.8 years of age, 59.4% men), registered in the Kyushu
      Prevention Study for Atherosclerosis. Patients were divided into 3 groups
      according to the value of ABI at baseline: ABI <=0.90 (abnormal ABI:354
      patients), 0.91 <= ABI <= 0.99 (borderline ABI:333 patients), and 1.00 <= ABI <=
      1.40 (normal ABI:3294 patients). RESULTS: Cumulative incidence of all-cause death
      was significantly higher in patients with abnormal and borderline ABI than in
      those with normal ABI (34.4% vs. 13.5%, P < 0.0001 and 26.1% vs. 13.5%, P <
      0.0001, respectively). In multivariate analysis, the risks for all-cause death in
      patients with abnormal ABI (HR:2.16; 95%CI:1.46-3.14; P = 0.0002) and borderline
      ABI (HR:1.78; 95%CI:1.14-2.70; P = 0.01) were significantly higher than in those
      with normal ABI. The incidence of PAD was remarkably higher in patients with
      borderline ABI than in those with normal ABI (32.2% vs.9.6%, P < 0.0001). After
      adjustment, the risk for PAD was significantly higher in patients with borderline
      ABI than in those with normal ABI (HR:3.10; 95%CI:1.90-4.95; P < 0.0001).
      CONCLUSIONS: Borderline ABI in diabetic patients was associated with
      significantly higher risks for mortality and PAD compared with normal ABI.

PMID- 24732576
TI  - Adjunctive application of chlorhexidine and ethanol-wet bonding on durability of
      bonds to sound and caries-affected dentine.
AB  - OBJECTIVES: To examine the effect of adjunctive application of chlorhexidine
      (CHX) and ethanol-wet bonding (EWB) on bond durability and nanoleakage of
      hydrophobic adhesive to sound (SD) and caries-affected dentine (CAD). METHODS:
      Dentine surfaces of molars were etched after caries removal and randomly
      allocated to four groups (n=12). In Groups 1 and 2, dentine surfaces were
      saturated with either 2 ml of 100% ethanol or 2 ml of ethanol with 2% CHX for
      60s. In Groups 3 and 4, dentine surfaces were saturated with either 15 MUL of
      distilled water or 15 MUL of distilled water with 2% CHX for 60s. Two coats of
      primer, followed by neat resin were applied and light-cured for 40s. Resin
      composite build-ups were placed and bonded specimens were sectioned for bond
      strength testing after 24 h and 12 months' storage in artificial saliva. Bond
      strength data were analyzed using 3-way ANOVA and SNK tests. Interfacial
      nanoleakage was evaluated after 24 h and 12 months using a field-emission
      scanning electron microscopy and data were analyzed using Kruskal-Wallis test.
      RESULTS: Significant differences were observed for the three factors: "substrate"
      (p<0.001), "rewetting agents" (p<0.001) and "time" (p<0.001) on bond strength.
      Incorporation of 2% CHX to EWB preserved bond strength to SD and CAD and reduced
      interfacial nanoleakage after 12 months. Incorporation of 2% CHX to WWB also
      preserved bond strength to SD after ageing. CONCLUSIONS: Incorporation of
      chlorhexidine to ethanol-wet bonding has an interaction effect on preservation of
      bond durability to sound and caries-affected dentine. CLINICAL SIGNIFICANCE:
      Incorporation of chlorhexidine to ethanol-wet bonding with hydrophobic adhesive
      enhances the success rate of aesthetic bonded restorations.

PMID- 24732577
TI  - Spontaneous self-assembly of SC3 hydrophobins into nanorods in aqueous solution.
AB  - Hydrophobins are small surface active proteins secreted by filamentous fungi.
      Because of their ability to self-assemble at hydrophilic-hydrophobic interfaces,
      hydrophobins play a key role in fungal growth and development. In the present
      work, the organization in aqueous solution of SC3 hydrophobins from the fungus
      Schizophyllum commune was assessed using Dynamic Light Scattering, Atomic Force
      Microscopy and fluorescence spectroscopy. These complementary approaches have
      demonstrated that SC3 hydrophobins are able not only to spontaneously self
      assemble at the air-water interface but also in pure water. AFM experiments
      evidenced that hydrophobins self-assemble in solution into nanorods. Fluorescence
      assays with thioflavin T allowed establishing that the mechanism governing SC3
      hydrophobin self-assembly into nanorods involves beta-sheet stacking. SC3
      assembly was shown to be strongly influenced by ionic strength and solution pH.
      The presence of a very low ionic strength significantly favoured the protein self
      assembly but a further increase of ions in solution disrupted the protein
      assembly. It was assessed that solution pH had a significant effect on the SC3
      hydrophobins organization. In peculiar, the self-assembly process was
      considerably reduced at acidic pH. Our findings demonstrate that the self
      assembly of SC3 hydrophobins into nanorods of well-defined length can be directly
      controlled in solution. Such control allows opening the way for the development
      of new smart self-assembled structures for targeted applications. 

PMID- 24732578
TI  - A single amino acid in VP2 is critical for the attachment of infectious bursal
      disease subviral particles to immobilized metal ions and DF-1 cells.
AB  - VP2 protein is the primary host-protective immunogen of infectious bursal disease
      virus (IBDV). His249 and His253 are two surface histidine residues in IBDV
      subviral particles (SVP), which is formed by twenty VP2 trimers when the VP2
      protein of a local isolate is expressed. Here, a systemic study was performed to
      investigate His249 or/and His253 on self-assembly, cell attachment and
      immunogenicity of SVP. Point-mutagenesis of either or both histidine residues to
      alanine did not affect self-assembly of the SVP, but the SVP lost its Ni-NTA
      binding affinity when the His253 was mutated. Indirect immunofluorescence assays
      and inhibitory experiments also showed that His253 is essential for SVP to attach
      onto the DF-1 cells and to inhibit IBDV infection of DF-1 cells. Finally, enzyme
      linked immunosorbent assays and chicken protection assays demonstrated that SVP
      with a mutation of His253 to alanine induced comparable neutralizing antibody
      titers in chickens as the wild-type SVP did. It was concluded that VP2's His253,
      a site not significant for the overall immunogenicity induced by SVP, is crucial
      for the binding affinity of SVP to Ni-NTA and the attachment of an IBDV host cell
      line. This is the first paper to decipher the role of His253 played in receptor
      interaction and immunogenicity. 

PMID- 24732580
TI  - Mitochondrial alterations in apoptosis.
AB  - Besides their conventional role as energy suppliers for the cell, mitochondria in
      vertebrates are active regulators of apoptosis. They release apoptotic factors
      from the intermembrane space into the cytosol through a mechanism that involves
      the Bcl-2 protein family, mediating permeabilization of the outer mitochondrial
      membrane. Associated with this event, a number of additional changes affect
      mitochondria during apoptosis. They include loss of important mitochondrial
      functions, such as the ability to maintain calcium homeostasis and to generate
      ATP, as well as mitochondrial fragmentation and cristae remodeling. Moreover, the
      lipidic component of mitochondrial membranes undergoes important alterations in
      composition and distribution, which have turned out to be relevant regulatory
      events for the proteins involved in apoptotic mitochondrial damage. 

PMID- 24732579
TI  - Estrogen receptor alpha variants affect age at onset of Alzheimer's disease in a
      multiethnic female cohort.
AB  - BACKGROUND/AIMS: Few studies of gene variants that affect estrogen activity
      investigate their association with age at onset of Alzheimer's disease (AD) in
      women of different ethnicities. We examined the influence of ESR1 polymorphisms
      on age at onset of AD in a multiethnic cohort of women. METHODS: Among 1,436
      women participating in the Washington Heights Inwood Columbia Aging Project,
      association with age at AD onset was assessed for 41 single-nucleotide
      polymorphisms (SNPs) on the ESR1 gene using Cox proportional hazard models,
      adjusting for presence of an APOE epsilon4 allele, years of education, and body
      mass index. RESULTS: Six SNPs in self-identified White women were protectively
      associated with delayed age of AD onset in this self-identified group, including
      the two restriction fragment length polymorphisms PvuII (rs2234693) and XbaI
      (rs9340799) (HR range = 0.420-0.483). Two separate SNPs were found to affect age
      of AD onset in self-identified Black women. CONCLUSIONS: ESR1 polymorphisms
      affect age of onset of AD in women, and risk alleles vary by ethnicity. These
      effects are possibly due to different linkage disequilibrium patterns or
      differences in comorbid environmental or cultural risk factors mediating the SNP
      effect on risk for AD.

PMID- 24732581
TI  - Insights into the role of cyclic ladderane lipids in bacteria from computer
      simulations.
AB  - Ladderanes, which are multiple fused cyclobutane rings, are unique structures
      available only in nature. Anammox bacteria produce ladderane phospholipids during
      their life cycle, but the synthesis mechanism still remains a mystery. The
      function of ladderane lipids in the membrane is unclear as well. According to
      previous speculations, ladderane moieties of the bilayer might decrease
      permeability for certain molecules, which should not diffuse out of the
      compartment enclosed by the ladderane-containing membrane. We report the first
      atomistic-precision molecular dynamics simulations of bilayers containing
      ladderane lipids. The structural and thermodynamics differences among (1) pure
      ladderane containing bilayer, (2) POPC bilayer, and (3) their equimolar mixture
      are discussed. Potentials of mean force are reported for the translocation of a
      hydrazine molecule through all investigated bilayers. All bilayers offer a
      potential energy barrier to hydrazine. Contrary to expectations, the presence of
      the ladderane lipids somewhat lowers the barrier for translocation of hydrazine.
      We conclude that the presence of ladderane phospholipids in anammox bacteria does
      not serve as a barrier to hydrazine. It may serve as a barrier to larger and
      noxious intermediates in the anammox reaction, or, the true mission of ladderane
      lipids must be located in a different plane. 

PMID- 24732582
TI  - Purification and characterisation of recombinant human eukaryotic elongation
      factor 1 gamma.
AB  - The eukaryotic elongation factor 1 gamma (eEF1gamma) is a multi-domain protein,
      which consist of a glutathione transferase (GST)-like N-terminus domain. In
      association with alpha, beta and delta subunits, eEF1gamma forms part of the
      eukaryotic elongation factor complex, which is mainly involved in protein
      biosynthesis. The N-terminus GST domain of eEF1gamma interacts with the beta
      subunit. eEF1gamma subunit is over-expressed in human carcinoma. The role of
      human eEF1gamma (heEF1gamma) is poorly understood. A successful purification of
      recombinant heEF1gamma is the first step towards determining unknown properties
      of the protein, including putative GST-like activities and the structure of the
      protein. This paper describes the over-expression, purification and
      characterisation of recombinant full-length, and the N- and C-terminus domains of
      heEF1gamma. All three recombinant heEF1gamma constructs over-expressed in the
      soluble Escherichia coli cell fraction and were purified to homogeneity.
      Secondary structure analysis indicates that the heEF1gamma constructs have high
      alpha-helical structural character. The full-length and N-terminus domain are
      dimeric, while the C-terminus is monomeric. Both full-length and N-terminus
      domain interact with 8-anilino-1-naphthalene sulfonate (ANS) with KD=70.0 (+/
      5.7) MUM and with reduced glutathione (GSH). Glutathione sulfonate displaced ANS
      bound to hydrophobic binding sites in the recombinant N-terminus domain. Using
      the standard GSH-1-chloro-2,4-dinitrobenzene conjugation assay, the N-domain
      showed some enzyme activity (0.03MUmolmin(-1) mg(-1) protein), while the full
      length heEF1gamma did not catalyse the GSH-CDNB conjugation. Consequently, we
      hypothesize the presence of a presumed GST-like active site structure in the
      heEF1gamma, which comprises a glutathione binding site and a hydrophobic
      substrate binding site. 

PMID- 24732583
TI  - A meta-analysis of circulating homocysteine levels in subjects with versus
      without abdominal aortic aneurysm.
AB  - The aim of this paper was to summarize the present evidence for an association
      between circulating total homocysteine (tHcy) levels and abdominal aortic
      aneurysm (AAA) presence, we performed a meta-analysis. MEDLINE and EMBASE were
      searched through December 2013. Search terms included homocysteine,
      hyperhomocysteinemia, hyperhomocysteinaemia, and abdominal aortic aneurysm.
      Eligible studies were case-control or population-screening studies reporting
      circulating tHcy levels in cases with AAA and subjects without AAA. For each
      study, data regarding plasma or serum tHcy levels in both the AAA and control
      groups were used to generate standardized mean differences (SMDs) and 95%
      confidence intervals (CIs). Further, adjusted and unadjusted odds ratios (ORs)
      with 95% CI of AAA incidence for subjects with hyperhomocysteinemia were
      extracted. Of 42 potentially relevant articles screened initially, 9 eligible
      studies enrolling 1643 cases with AAA and 5460 subjects without AAA were
      identified and included. A pooled analysis demonstrated significantly greater
      circulating tHcy levels in the AAA than control group (SMD, 0.58; 95% CI, 0.36 to
      0.79; P<0.00001). Another pooled analysis demonstrated a statistically
      significant 3.1-fold increase in AAA incidence for subjects with
      hyperhomocysteinemia (OR, 3.07; 95% CI, 1.59 to 5.92; P=0.0008). In conclusion,
      greater circulating tHcy levels are associated with AAA presence. 

PMID- 24732584
TI  - Antioxidant agents help primary Raynaud's phenomenon.

PMID- 24732585
TI  - CVD: a condition of underestimated severity.
AB  - Chronic venous disease (CVD) affects approximately a quarter of the adult
      population and causes a considerable burden on the health of these patients. The
      true extent of the severity of the disease is hampered because of reduced public
      awareness, operational difficulties in diagnosis, and the perception that
      varicose veins are mainly a cosmetic inconvenience. Consequently the disease
      receives little attention in public health care systems which focus on life
      threatening conditions and those which cause obvious morbidity like cancer,
      cardiac disease and stroke. This review aims to correct these misconceptions by
      addressing the full scope of CVD, including the post-thrombotic syndrome and
      venous ulceration. The severity of conditions like telangectasiae and edema and
      the symptoms they cause are frequently underestimated, especially if varicose
      veins are not present to alert the patient or doctor. The definition, diagnosis,
      scope, epidemiology, progression and cost of CVD are discussed with evidence to
      explain how these underestimate the severity of the disease. It is anticipated
      that once CVD achieves greater recognition this will open up greater
      opportunities for treatment. These include surgery, endovenous ablation,
      stenting, compression, venoactive drugs like micronized purified flavonoid
      fraction and other drugs such as sulodexide and pentoxifylline. 

PMID- 24732586
TI  - Vascular injuries in supracondylar humeral fracture: an active approach to
      diagnosis and treatment.
AB  - AIM: The strategy with vascular complications of supracondylar humeral fractures
      (SHF) is under scrutiny since modern diagnostic techniques, particularly
      ultrasound investigations, provide earlier and more precise assessment and
      updated vascular surgical procedures, particularly microvascular ones, obtain
      excellent results. The purpose of this study was to look prospectively at what
      could be achieved by early systematic diagnostic investigations and, when
      appropriate, immediate arterial exploration and repair. METHODS: Sixty-three
      pediatric patients with SHF were admitted and treated in our Service between
      January 2007 and February 2014. Besides clinical examination, they were all
      investigated by color-coded Duplex scanning (CCDS) and ultrasound velocimetry
      (UV) of the hand. Eighteen patients were pulseless at first observation. Seven of
      them presented without signs of ischemia and regained their pulse post-reduction;
      only dislodgement and compression of the brachial artery (BA) was found in those
      children. In 11 patients, with pink hand in 7 and severe ischemia (white
      pulseless hand) in 4, lesions of the BA were detected. All were operated upon by
      various forms of arterial repair. CCDS and UV were used also intraoperatively and
      during follow-up (1 m-13 y). RESULTS: All patients had favorable early and long
      term results: 8 came back to normal conditions, 2 had persistent paresthesia and
      weakness of the hand and 1 remained with partial disability of forearm and hand.
      All BA remained patent. CCDS correctly detected all the lesions preoperatively
      and showed the patency of the arteries after repair. CONCLUSION: Early
      assessment, use of ultrasound investigations and BA prompt repair seem to be the
      most logical and fruitful strategy at present time.

PMID- 24732587
TI  - Vascular histone deacetylation by pharmacological HDAC inhibition.
AB  - HDAC inhibitors can regulate gene expression by post-translational modification
      of histone as well as nonhistone proteins. Often studied at single loci,
      increased histone acetylation is the paradigmatic mechanism of action. However,
      little is known of the extent of genome-wide changes in cells stimulated by the
      hydroxamic acids, TSA and SAHA. In this article, we map vascular chromatin
      modifications including histone H3 acetylation of lysine 9 and 14 (H3K9/14ac)
      using chromatin immunoprecipitation (ChIP) coupled with massive parallel
      sequencing (ChIP-seq). Since acetylation-mediated gene expression is often
      associated with modification of other lysine residues, we also examined H3K4me3
      and H3K9me3 as well as changes in CpG methylation (CpG-seq). RNA sequencing
      indicates the differential expression of ~30% of genes, with almost equal numbers
      being up- and down-regulated. We observed broad deacetylation and gene expression
      changes conferred by TSA and SAHA mediated by the loss of EP300/CREBBP binding at
      multiple gene promoters. This study provides an important framework for HDAC
      inhibitor function in vascular biology and a comprehensive description of genome
      wide deacetylation by pharmacological HDAC inhibition. 

PMID- 24732588
TI  - Extensive and coordinated control of allele-specific expression by both
      transcription and translation in Candida albicans.
AB  - Though sequence differences between alleles are often limited to a few
      polymorphisms, these differences can cause large and widespread allelic variation
      at the expression level. Such allele-specific expression (ASE) has been
      extensively explored at the level of transcription but not translation. Here we
      measured ASE in the diploid yeast Candida albicans at both the transcriptional
      and translational levels using RNA-seq and ribosome profiling, respectively.
      Since C. albicans is an obligate diploid, our analysis isolates ASE arising from
      cis elements in a natural, nonhybrid organism, where allelic effects reflect
      evolutionary forces. Importantly, we find that ASE arising from translation is of
      a similar magnitude as transcriptional ASE, both in terms of the number of genes
      affected and the magnitude of the bias. We further observe coordination between
      ASE at the levels of transcription and translation for single genes.
      Specifically, reinforcing relationships--where transcription and translation
      favor the same allele--are more frequent than expected by chance, consistent with
      selective pressure tuning ASE at multiple regulatory steps. Finally, we
      parameterize alleles based on a range of properties and find that SNP location
      and predicted mRNA-structure stability are associated with translational ASE in
      cis. Since this analysis probes more than 4000 allelic pairs spanning a broad
      range of variations, our data provide a genome-wide view into the relative impact
      of cis elements that regulate translation.

PMID- 24732589
TI  - Tumor-suppressive functions of 15-Lipoxygenase-2 and RB1CC1 in prostate cancer.
AB  - 15-Lipoxygenase-2 (15-LOX2) is a human-specific lipid-peroxidizing enzyme most
      prominently expressed in epithelial cells of normal human prostate but
      downregulated or completely lost in>70% of prostate cancer (PCa) cases.
      Transgenic expression of 15-LOX2 in the mouse prostate surprisingly causes
      hyperplasia. Here we first provide evidence that 15-LOX2-induced prostatic
      hyperplasia does not progress to PCa even in p53(+/-) or p53(-/-) background.
      More important, by generating 15-LOX2; Hi-Myc double transgenic (dTg) mice, we
      show that 15-LOX2 expression inhibits Myc-induced PCa development, such that in
      the 3-month- and 6-month-old dTg mice, there is a significant reduction in
      prostate intraneoplasia (PIN) and PCa prevalent in age-matched Hi-Myc prostates.
      The dTg prostates show increased cell senescence and expression of several
      senescence-associated molecules, including p27, phosphorylated Rb, and Rb1cc1. We
      further show that in HPCa, 15-LOX2 and c-Myc manifest reciprocal protein
      expression patterns. Moreover, RB1CC1 accumulates in senescing normal human
      prostate (NHP) cells, and in both NHP and RWPE-1 cells, the 15-LOX2 metabolic
      products 15(S)-HPETE and 15(S)-HETE induce RB1CC1. We finally show that unlike 15
      LOX2, RB1CC1 is not lost but rather frequently overexpressed in PCa samples.
      RB1CC1 knockdown in PC3 cells enhances clonal growth in vitro and tumor growth in
      vivo. Together, our present studies provide evidence for tumor-suppressive
      functions for both 15-LOX2 and RB1CC1. 

PMID- 24732591
TI  - Associations of activity monitor output and an estimate of aerobic fitness with
      pulse wave velocities: the Nakanojo study.
AB  - BACKGROUND: We examined the relative contributions of habitual physical activity
      and aerobic fitness to the prevention of arteriosclerosis. METHODS: Elderly
      individuals (97 men and 109 women, aged > 65 y) each wore a uniaxial activity
      monitor continuously for 1 year, with activity data summarized as an average
      daily step count and duration of activity > 3 metabolic equivalents (METs).
      Aerobic fitness was assessed by a standardized 5-m walking test measure of
      maximal walking speed. Central arterial stiffness was determined using an
      automatic waveform analyzer measure of cardio-femoral pulse wave velocity
      (cfPWV). RESULTS: The cfPWV was negatively associated with daily step count,
      duration of activity > 3 METs, and maximal walking speed (P < .05). Multiple
      stepwise regression analysis revealed that the step count, duration of activity >
      3 METs, and maximal walking speed were all significant predictors of cfPWV,
      accounting for 11%, 7%, and 4% of total variance, respectively. CONCLUSIONS: In
      contrast to findings from studies using potentially fallible questionnaires, our
      data suggest that a measure of health (arterial stiffness) is more closely
      related to objective measures of physical activity than to an estimate of aerobic
      fitness.

PMID- 24732590
TI  - Adventitial delivery of lentivirus-shRNA-ADAMTS-1 reduces venous stenosis
      formation in arteriovenous fistula.
AB  - Hemodialysis vascular access can develop venous neointimal hyperplasia (VNH)
      causing stenosis. Recent clinical and experimental data has demonstrated that
      there is increased expression of a disintegrin and metalloproteinase
      thrombospondin motifs-1 (ADAMTS-1) at site of VNH. The experiments outlined in
      the present paper were designed to test the hypothesis that targeting of the
      adventitia of the outflow vein of murine arteriovenous fistula (AVF) using a
      small hairpin RNA that inhibits ADAMTS-1 expression (LV-shRNA-ADAMTS-1) at the
      time of fistula creation will decrease VNH. At early time points, ADAMTS-1
      expression was significantly decreased associated with a reduction in vascular
      endothelial growth factor-A (VEGF-A) and matrix metalloproteinase-9 (MMP-9) (LV
      shRNA-ADAMTS-1 transduced vessels vs. controls). These changes in gene and
      protein expression resulted in favorable vascular remodeling with a significant
      increase in mean lumen vessel area, decrease in media/adventitia area, with a
      significant increase in TUNEL staining accompanied with a decrease in cellular
      proliferation accompanied with a reduction in CD68 staining. Collectively, these
      results demonstrate that ADAMTS-1 transduced vessels of the outflow vein of AVF
      have positive vascular remodeling. 

PMID- 24732592
TI  - High level of soluble programmed cell death ligand 1 in blood impacts overall
      survival in aggressive diffuse large B-Cell lymphoma: results from a French
      multicenter clinical trial.
AB  - The dosage of soluble programmed cell death ligand 1 (sPD-L1) protein in the
      blood of adults with cancer has never been performed in a prospective patient
      cohort. We evaluated the clinical impact of sPD-L1 level measured at the time of
      diagnosis for newly diagnosed diffuse large B-cell lymphoma (DLBCL). Soluble PD
      L1 was measured in the plasma of 288 patients enrolled in a multicenter,
      randomized phase III trial that compared R-high-dose chemotherapy with R-CHOP.
      The median follow-up was 41.4 months. A cutoff of 1.52 ng/ml of PD-L1 level was
      determined and related to overall survival (OS). Patients with elevated sPD-L1
      experienced a poorer prognosis with a 3-year OS of 76% versus 89% (P<0.001).
      Considering clinical characteristics, the multivariate analysis retained this
      biomarker besides bone marrow involvement and abnormal lymphocyte-monocyte score
      as independently related to poor outcome. sPD-L1 was detectable in the plasma and
      not in the serum, found elevated in patients at diagnosis compared with healthy
      subjects and its level dropped back to normal value after CR. The intention-to
      treat analysis showed that elevated sPD-L1 was associated with a poorer prognosis
      for patients randomized within the R-CHOP arm (P<0.001). Plasma PD-L1 protein is
      a potent predicting biomarker in DLBCL and may indicate usefulness of alternative
      therapeutic strategies using PD-1 axis inhibitors. 

PMID- 24732593
TI  - Analysis of calreticulin mutations in Chinese patients with essential
      thrombocythemia: clinical implications in diagnosis, prognosis and treatment.

PMID- 24732595
TI  - piRNA-823 contributes to tumorigenesis by regulating de novo DNA methylation and
      angiogenesis in multiple myeloma.
AB  - Aberrant DNA hypermethylation contributes to myelomagenesis by silencing tumor
      suppressor genes. Recently, a few reports have suggested that a novel class of
      small non-coding RNAs, called Piwi-interacting RNAs (piRNAs), may be involved in
      the epigenetic regulation of cancer. In this study, for the first time we
      provided evidence that the expression of piRNA-823 was upregulated in multiple
      myeloma (MM) patients and cell lines, and positively correlated with clinical
      stage. Silencing piRNA-823 in MM cells induced deregulation of cell cycle
      regulators and apoptosis-related proteins expression, accompanied by inhibition
      of tumorigenicity in vitro and in vivo. Moreover, piRNA-823 was directly relevant
      to de novo DNA methyltransferases, DNMT3A and 3B, in primary CD138(+) MM cells.
      The inhibited expression of piRNA-823 in MM cells resulted in marked reduction of
      DNMT3A and 3B at both mRNA and protein levels, which in turn led to decrease in
      global DNA methylation and reexpression of methylation-silenced tumor suppressor,
      p16(INK4A). In addition, piRNA-823 abrogation in MM cells induced reduction of
      vascular endothelial growth factor secretion, with consequent decreased
      proangiogenic activity. Altogether, these data support an oncogenic role of piRNA
      823 in the biology of MM, providing a rational for the development of piRNA
      targeted therapeutic strategies in MM. 

PMID- 24732594
TI  - Allele-specific loss and transcription of the miR-15a/16-1 cluster in chronic
      lymphocytic leukemia.
AB  - Deregulation of the miR-15a/16-1 cluster has a key role in the pathogenesis of
      chronic lymphocytic leukemia (CLL), a clinically heterogeneous disease with
      indolent and aggressive forms. The miR-15a/16-1 locus is located at 13q14, the
      most frequently deleted region in CLL. Starting from functional investigations of
      a rare SNP upstream the miR cluster, we identified a novel allele-specific
      mechanism that exploits a cryptic activator region to recruit the RNA polymerase
      III for miR-15a/16-1 transcription. This regulation of the miR-15a/16- locus is
      independent of the DLEU2 host gene, which is often transcribed monoallellically
      by RPII. We found that normally one allele of miR-15a/16-1 is transcribed by
      RNAPII, the other one by RNAPIII. In our subset of CLL patients harboring 13q14
      deletions, exclusive RNA polymerase III (RPIII)-driven transcription of the miR
      15a/16-1 was the consequence of loss of the RPII-regulated allele and correlated
      with high expression of the poor prognostic marker ZAP70 (P=0.019). Thus, our
      findings point to a novel biological process, characterized by double allele
      specific transcriptional regulation of the miR-15a/16-1 locus by alternative
      mechanisms. Differential usage of these mechanisms may distinguish at onset
      aggressive from indolent forms of CLL. This provides a basis for the clinical
      heterogeneity of the CLL patients carrying 13q14 deletions. 

PMID- 24732596
TI  - Impaired hematopoietic differentiation of RUNX1-mutated induced pluripotent stem
      cells derived from FPD/AML patients.
AB  - Somatic mutation of RUNX1 is implicated in various hematological malignancies,
      including myelodysplastic syndrome and acute myeloid leukemia (AML), and previous
      studies using mouse models disclosed its critical roles in hematopoiesis.
      However, the role of RUNX1 in human hematopoiesis has never been tested in
      experimental settings. Familial platelet disorder (FPD)/AML is an autosomal
      dominant disorder caused by germline mutation of RUNX1, marked by
      thrombocytopenia and propensity to acute leukemia. To investigate the
      physiological function of RUNX1 in human hematopoiesis and pathophysiology of
      FPD/AML, we derived induced pluripotent stem cells (iPSCs) from three distinct
      FPD/AML pedigrees (FPD-iPSCs) and examined their defects in hematopoietic
      differentiation. By in vitro differentiation assays, FPD-iPSCs were clearly
      defective in the emergence of hematopoietic progenitors and differentiation of
      megakaryocytes, and overexpression of wild-type (WT)-RUNX1 reversed most of these
      phenotypes. We further demonstrated that overexpression of mutant-RUNX1 in WT
      iPSCs did not recapitulate the phenotype of FPD-iPSCs, showing that the mutations
      were of loss-of-function type. Taken together, this study demonstrated that
      haploinsufficient RUNX1 allele imposed cell-intrinsic defects on hematopoietic
      differentiation in human experimental settings and revealed differential impacts
      of RUNX1 dosage on human and murine megakaryopoiesis. FPD-iPSCs will be a useful
      tool to investigate mutant RUNX1-mediated molecular processes in hematopoiesis
      and leukemogenesis. 

PMID- 24732597
TI  - Gene expression profile alone is inadequate in predicting complete response in
      multiple myeloma.
AB  - With advent of several treatment options in multiple myeloma (MM), a selection of
      effective regimen has become an important issue. Use of gene expression profile
      (GEP) is considered an important tool in predicting outcome; however, it is
      unclear whether such genomic analysis alone can adequately predict therapeutic
      response. We evaluated the ability of GEP to predict complete response (CR) in
      MM. GEP from pretreatment MM cells from 136 uniformly treated MM patients with
      response data on an IFM, France led study were analyzed. To evaluate variability
      in predictive power due to microarray platform or treatment types, additional
      data sets from three different studies (n=511) were analyzed using same methods.
      We used several machine learning methods to derive a prediction model using
      training and test subsets of the original four data sets. Among all methods
      employed for GEP-based CR predictive capability, we got accuracy range of 56-78%
      in test data sets and no significant difference with regard to GEP platforms,
      treatment regimens or in newly diagnosed or relapsed patients. Importantly,
      permuted P-value showed no statistically significant CR predictive information in
      GEP data. This analysis suggests that GEP-based signature has limited power to
      predict CR in MM, highlighting the need to develop comprehensive predictive model
      using integrated genomics approach. 

PMID- 24732598
TI  - Deferoxamine promotes MDA-MB-231 cell migration and invasion through increased
      ROS-dependent HIF-1alpha accumulation.
AB  - BACKGROUND/AIM: Deferoxamine (DFO), an iron chelator, has been reported to induce
      hypoxia-inducible factor-1alpha (HIF-1alpha) expression. HIF-1alpha plays a
      critical role in promoting tumor metastasis. However, the molecular mechanisms
      underlying induction of HIF-1alpha in breast cancer cells remain unknown. Our aim
      was to ascertain whether DFO enhanced cancer metastasis in MDA-MB-231 cells.
      METHODS: Cellular reactive oxygen species (ROS) was measured by flow cytometry.
      Cell migration was determined by wound healing and transwell assays. Protein and
      mRNA expression were detected by western blotting and RT-PCR, respectively.
      RESULTS: DFO treatment enhanced cell migration and invasion, while HIF-1alpha
      expression was significantly up-regulated at the post-transcriptional level.
      However, treatment with a NADPH oxidase inhibitor, diphenyleneiodonium (DPI),
      strongly inhibited ROS generation and HIF-1alpha expression, as well as cell
      migration and invasion. Notably, DFO treatment increased extracellular signal
      regulated kinase (ERK)1/2 phosphorylation. Inhibition of ROS production with DPI
      attenuated DFO-induced ERK1/2 activation. Moreover, a MEK1 inhibitor, PD98059,
      suppressed DFO-induced cell migration and invasion. CONCLUSION: DFO-induced HIF
      1alpha expression involves a cascade of signaling events including ROS
      generation, activation of ERK signaling, and subsequent promotion of cell
      migration and invasion. These findings indicate a risk associated with DFO and
      other iron chelators for treatment of tumors with invasive potential.

PMID- 24732599
TI  - Facet dependent binding and etching: ultra-sensitive colorimetric visualization
      of blood uric acid by unmodified silver nanoprisms.
AB  - By combination of experiments and density functional theory calculations, we
      present a simple but effective "facet dependent binding and etching" strategy for
      non-enzymatic and non-aggregated colorimetric sensing of blood uric acid (UA),
      using unmodified Ag nanoprisms as the signal readout. In the absence of UA, the
      triangular Ag nanoprisms are etched alongside (110) facets by H2O2 and form round
      nanodiscs, and a more than 160 nm surface plasmon resonance (SPR) blue shift is
      observed. Because of special affinity between UA and side facets of the Ag
      nanoprisms, pre-added UA can well protect the Ag nanoprisms from etching. Such
      protection effect can be used for well quantifying UA in the range of 10-3000 nM,
      based on the inverse proportion of the SPR blue shift with the added analyte. Due
      to very thin plate morphology (5 nm) and facet dependent binding/etching effects
      of the Ag nanoprisms, the sensing system has ultrahigh sensitivity. The detection
      limit is only 10nM, which is about 2 to 4 orders of magnitude lower than that of
      previous colorimetric sensing systems. In addition to accurate quantitation, the
      proposed strategy can conveniently discriminate the patient of hyperuricemia from
      normal person by naked eyes. So, the present simple, low-cost and visualized UA
      chemosensor has great potential in the applications for point-of-care
      diagnostics.

PMID- 24732600
TI  - Detection of the antiepileptic drug phenytoin using a single free-standing
      piezoresistive microcantilever for therapeutic drug monitoring.
AB  - Phenytoin, one of the most widely used antiepileptic drugs, suppresses the
      abnormal brain activity often seen in seizures. In this study, we report the
      electrical detection of phenytoin as an antiepileptic medication with a narrow
      therapeutic dosage range to which therapeutic drug monitoring (TDM) is applied.
      The measurement technique used an electrical detection of a piezoresistive
      microcantilever biosensor. This label-free, electrically measured microcantilever
      can be miniaturized in order to be portable for point-of-care, personal diagnosis
      or for personalized therapeutic drug monitoring. The miniaturized piezoresistive
      microcantilever was fabricated by micro-electro-mechanical system processes, and
      was integrated into a microfluidic channel with a system for label-free
      detection. The microcantilever biosensor was approved for the detection of
      phenytoin in solutions of deionized water and 100% fetal bovine serum. A linear
      profile in a drug-concentration range of 10-80 MUg/mL was detected, with the
      signal resolution being about 0.005 Omega. The concentration sensitivity was
      2.94*10(-6) (MUg/mL)(-1). The binding affinity (KD) was calculated to be 58
      MUg/mL. The results of the present piezoresistive microcantilever biosensors
      showed a solid correlation of phenytoin drug detection with that in the
      clinically used fluorescence polarization immunoassay (FPIA).

PMID- 24732601
TI  - Universal biosensor for detection of influenza virus.
AB  - Influenza is a contagious disease caught by humans caused by viruses belonging to
      the family Orthomyxoviridae. Each year, the influenza virus infects millions of
      people and kills hundreds of thousands of them. Traditional diagnostic methods,
      such as virus propagation and isolation, antigen capture immunoassays and
      molecular methods are not sufficient for the detection of the influenza virus.
      Development of a valid diagnostic assay for quick detection (in less than an
      hour) of the virus, with high sensitivity, is a challenge for researchers all
      over the world. Here we present a new, universal immunosensor for detection of
      the influenza A virus. By using electrochemical impedance spectroscopy (EIS) and
      direct attachment of antibodies to the gold electrode the assay allows detection
      of the pathogen with sensitivity similar to molecular methods in relatively short
      time. Application of universal anti-M1 antibodies allows detection of all
      serotypes of influenza A virus. The simple design of the sensor facilitates
      miniaturization of the device and its implementation for routine diagnostics
      during first contact with the patient, before applying a proper treatment. 

PMID- 24732602
TI  - Novel helical TiO2 nanotube arrays modified by Cu2O for enzyme-free glucose
      oxidation.
AB  - A helical TiO2 nanotube (TNT) array modified with cuprous oxide (Cu2O) electrode
      was fabricated and used for nonenzymatic glucose detection. The structure and
      morphology of Cu2O/TNT were characterized by X-ray diffraction and transmission
      electron microscopy. The electrocatalytic performance of Cu2O/TNT electrode for
      glucose oxidation was investigated by cyclic voltammetry and chronoamperometry.
      At an applied potential of +0.65 V versus SCE, a linear range was obtained within
      the concentration range of 3.0-9.0 mM with a detection limit of 62 MUM
      (signal/noise=3). The response time was approximately 3 s after adding 0.10 mM
      glucose. Formate and gluconic acid were identified as the main products of the
      glucose oxidation using (1)H NMR spectrometry. A possible mechanism for
      continuous glucose oxidation was also proposed.

PMID- 24732603
TI  - Total internal reflection (TIRF)-based quantification of procalcitonin for sepsis
      diagnosis--a point-of-care testing application.
AB  - A new, highly sensitive fluorescence immunoassay for a TIRF (total internal
      reflection)-based point-of-care testing (POCT) device was developed for the
      detection of procalcitonin (PCT), a specific and early marker for sepsis and
      microbial infections. The immunoassay was performed on a bench-top system that
      fulfilled all the necessary characteristics of a POCT application, including a
      short measurement time (<9 min), no sample pre-treatment requirements and
      application directly near patients. New rat monoclonal antibodies targeting PCT
      were screened and characterized. The best combinations of antibodies were then
      integrated into single-use cartridges, and the reduction of nonspecific binding
      was achieved by supplying suitable additives. Moreover, human recombinant PCT
      (hrPCT) for use as a standard was developed in the native form of hPCT in plasma
      (PCT1-116, PCT3-116). The assay achieves the required sensitivity range in human
      plasma to allow reliable differentiation between healthy persons and varying
      stages of infection severity (LOD=0.04 ng/mL; LOQ=0.12 ng/mL). Furthermore, the
      developed PCT assay can be applied in whole human blood with an adequate
      sensitivity (LOD=0.02 ng/mL; LOQ=0.09 ng/mL). To the best of our knowledge, this
      is the first diagnostic test for sepsis to use whole blood, which is a crucial
      requirement for POCT. We were able to detect native PCT in patient samples and
      showed a good correlation (R(2)=0.988) with the results of the Kryptor((r))
      device from BRAHMS, a state of the art device for the detection of PCT.

PMID- 24732604
TI  - The transformation of common office supplies into a low-cost optical biosensing
      platform.
AB  - By reassembling common office supplies, an optical biosensing system was
      developed. A laser pointer and the solar cell from a calculator were utilized in
      the developed optical biosensing system as the light source and signal
      transducer, respectively. For intuitive signal evaluation, a multimeter was used.
      The following two types of conventional enzymatic colorimetric assays were
      employed with the optical biosensing system: (i) the Trinder's reaction-based
      enzymatic assay; and (ii) the competitive enzyme-linked immunosorbent assay.
      These colorimetric assays were performed in reaction channels made from
      transparent polymer and glass. By matching the maximum absorption spectra of the
      colored end products from the assays with the emission spectra of the laser
      diodes, the biochemical reaction rate was manifested as a change in the intensity
      of the laser beam. This change was then converted by the solar cell into voltage
      and displayed on the connected multimeter. To verify the detection performance of
      the system, glucose and an osteoarthritis biomarker (urinary collagen type II C
      telopeptide fragments [uCTX-II]) were quantified. With glucose, the voltages
      registered were linearly correlated with the glucose concentration, from 0 to 10
      mM. Using a competitive immunoassay for uCTX-II, the system exhibited a
      calibration curve with a dynamic detection range between 1.3 and 10 ng/mL uCTX
      II. Given the advantages of the proposed biosensing system, including its high
      sensitivity, facile fabrication, and the high obtainability and cost
      effectiveness of the components used to make it, we expect that this study will
      provide a basis for the production of a low-cost optical biosensor.

PMID- 24732605
TI  - Amplified and selective detection of Ag+ ions based on electrically contacted
      enzymes on duplex-like DNA scaffolds.
AB  - In the present study, ultrasensitive detection of Ag(+) is demonstrated by a
      biocatalytic signal amplification system which is realized by only one DNA
      sequence based electrical contacted enzyme structure and the Au
      nanoparticles/Carbon nanodots (AuNPs/C-dots) composite immobilization platform.
      In the presence of Ag(+), with the interaction of cytosine-Ag(+)-cytosine (C
      Ag(+)-C), cytosine-rich DNA sequence labeled with methylene blue (MB) molecules
      near 5' end and Glucose Oxidase (GOx) at 3' end, has a self-hybridization and
      then forms a duplex-like structure which makes MB and GOx approach the AuNPs/C
      dots modified electrode. MB units can then act as a relay that electrically
      contacts GOx with the AuNPs/C-dots modified electrode and activate the
      bioelectrocatalyzed oxidation of glucose to glucose acid. In consequence, based
      on the bioelectrocatalyzed signal amplification on the AuNPs/C-dots platform,
      Ag(+) could be quantitatively detected in the range of 10(-11)-10(-5) M with a
      low detection limit of 3 pM. Also, there is an excellent selectivity against
      other interferential metal ions. The detection of Ag(+) ions was realized by
      Ag(+) self-induced conformational change of DNA scaffold which involved only one
      oligonucleotide showing its convenience and availability.

PMID- 24732606
TI  - Postoperative vision loss during off-pump coronary artery bypass grafting.

PMID- 24732607
TI  - Perioperative optic neuropathy in patients undergoing off-pump coronary artery
      bypass graft surgery.
AB  - AIMS AND OBJECTIVES: Perioperative optic neuropathy (PON) is a rare, but
      devastating complication following coronary artery bypass graft surgery (CABG).
      We performed a retrospective study of PON associated with off-pump CABG (OPCABG)
      to identify possible risk factors. MATERIALS AND METHODS: 1442 patients underwent
      OPCABG over a 10-month period from October 2008 to August 2009; PON was
      identified in four (0.28%) patients. A retrospective review of the charts was
      done to identify the patient characteristics, pre-operative status, intra
      operative details, and ophthalmic examination details. Friedman test was used to
      compare the hematocrit (Hct) and the mean arterial pressure (MAP) values across
      the three time periods: Pre-, intra- and post-operative periods. RESULTS: All
      four patients were male, diabetic, and in the age range 51-69 years. All patients
      noted unilateral or bilateral severe visual loss in the immediate post-operative
      period, which was permanent. All the four patients had statistically significant
      decrease in the Hct (P < 0.039) and mean arterial blood pressure (P < 0.018) in
      the intraoperative and post-operative period when compared to pre-operative
      value. CONCLUSIONS : PON is a rare but definite possibility in patients
      undergoing OPCABG. Diabetes mellitus may be a risk factor. Perioperative
      hemodynamic abnormalities like decrease in MAP and anemia may play a role in the
      development of PON in OPCABG.

PMID- 24732608
TI  - Goal-directed hemostatic therapy using the rotational thromboelastometry in
      patients requiring emergent cardiovascular surgery.
AB  - AIMS AND OBJECTIVES: We assessed the clinical impact of goal-directed coagulation
      management based on rotational thromboelastometry (ROTEM) in patients undergoing
      emergent cardiovascular surgical procedures. MATERIALS AND METHODS: Over a 2-year
      period, data from 71 patients were collected prospectively and blood samples were
      obtained for coagulation testing. Administration of packed red blood cells (PRBC)
      and hemostatic products were guided by an algorithm using ROTEM-derived
      information and hemoglobin level. Based on the amount of PRBC transfused, two
      groups were considered: High bleeders (>=5 PRBC; HB) and low bleeders (<5 PRBC;
      LB). Data were analyzed using Chi-square test, unpaired t-test and analysis of
      variance as appropriate. RESULTS: Pre-operatively, the HB group (n = 31) was
      characterized by lower blood fibrinogen and decreased clot amplitude at ROTEM
      compared with the LB group (n = 40). Intraoperatively, larger amounts of
      fibrinogen, fresh frozen plasma and platelets were required to normalize the
      coagulation parameters in the HB group. Post-operatively, the incidence of major
      thromboembolic and ischemic events did not differ between the two groups (<10%)
      and the observed in-hospital mortality was significantly less than expected by
      the Physiological and Operative Severity Score for the enumeration of Mortality
      and Morbidity (POSSUM score, 22% vs. 35% in HB and 5% vs. 13% in LB group).
      CONCLUSIONS: ROTEM-derived information is helpful to detect early coagulation
      abnormalities and to monitor the response to hemostatic therapy. Early goal
      directed management of coagulopathy may improve outcome after cardiovascular
      surgery.

PMID- 24732609
TI  - Anesthesia and cor triatriatum.
AB  - AIMS AND OBJECTIVES: Cor triatriatum sinistrum (CTS) and cor triatriatum dextrum
      (CTD) are rare congenital anomalies characterized by the presence of a perforated
      septum which divides the respective atrium into a proximal and distal chamber.
      This report reviews the perioperative course of patients with uncorrected cor
      triatriatum (CT) undergoing procedures requiring anesthesia. In addition, we
      performed a literature search that examines the experience of others regarding
      the peri-operative course of patients with CT. MATERIALS AND METHODS: A
      computerized search of a medical record database was conducted to identify
      patients with a clinical diagnosis of uncorrected CTD and CTS undergoing surgical
      procedures. Descriptive statistics were used. RESULTS: We identified 12 adult
      patients with asymptomatic CTS (n = 7) and CTD (n = 5) who underwent 23
      anesthetics. There were no perioperative complications which could be attributed
      directly to the anatomy of CT. CONCLUSIONS: Our observation and review of the
      literature suggest that patients with asymptomatic CT typically tolerate
      anesthesia and surgical procedures well.

PMID- 24732610
TI  - Hypertrophic cardiomyopathy: part 1 - introduction, pathology and
      pathophysiology.
AB  - Hypertrophic cardiomyopathy (HCM) is the most common genetic cardiovascular
      disease with many genotype and phenotype variations. Earlier terminologies,
      hypertrophic obstructive cardiomyopathy and idiopathic hypertrophic sub-aortic
      stenosis are no longer used to describe this entity. Patients present with or
      without left ventricular outflow tract (LVOT) obstruction. Resting or provocative
      LVOT obstruction occurs in 70% of patients and is the most common cause of heart
      failure. The pathology and pathophysiology of HCM includes hypertrophy of the
      left ventricle with or without right ventricular hypertrophy, systolic anterior
      motion of mitral valve, dynamic and mechanical LVOT obstruction, mitral
      regurgitation, diastolic dysfunction, myocardial ischemia, and fibrosis. Thorough
      understanding of pathology and pathophysiology is important for anesthetic and
      surgical management. 

PMID- 24732611
TI  - Minimally invasive cardiac surgery and transesophageal echocardiography.
AB  - Improved cosmetic appearance, reduced pain and duration of post-operative stay
      have intensified the popularity of minimally invasive cardiac surgery (MICS);
      however, the increased risk of stroke remains a concern. In conventional cardiac
      surgery, surgeons can visualize and feel the cardiac structures directly, which
      is not possible with MICS. Transesophageal echocardiography (TEE) is essential
      during MICS in detecting problems that require immediate correction.
      Comprehensive evaluation of the cardiac structures and function helps in the
      confirmation of not only the definitive diagnosis, but also the success of
      surgical treatment. Venous and aortic cannulations are not under the direct
      vision of the surgeon and appropriate positioning of the cannulae is not possible
      during MICS without the aid of TEE. Intra-operative TEE helps in the navigation
      of the guide wire and correct placement of the cannulae and allows real-time
      assessment of valvular pathologies, ventricular filling, ventricular function,
      intracardiac air, weaning from cardiopulmonary bypass and adequacy of the
      surgical procedure. Early detection of perioperative complications by TEE
      potentially enhances the post-operative outcome of patients managed with MICS. 

PMID- 24732613
TI  - Left atrial myxoma, ruptured chordae tendinae causing mitral regurgitation and
      coronary artery disease.
AB  - Mitral regurgitation is uncommon with left atrial myxoma. The echocardiographic
      assessment of presence of mitral regurgitation and its severity are impaired by
      the presence of left atrial myxoma. We describe an uncommon association of left
      atrial myxoma with coronary artery disease and mitral regurgitation. MR was
      reported as mild on pre-operative transthoracic echocardiography but found to be
      severe due to ruptured chordae tendinae during intra-operative transesophageal
      echocardiography, which lead to change in the surgical plan to mitral valve
      replacement in addition to excision of myxoma. 

PMID- 24732614
TI  - Paravalvular leak after mitral valve replacement: advantage of 3D echo.

PMID- 24732615
TI  - Ectatic coronary arteries in a patient with Noonan syndrome on transoesophageal
      echocardiography.

PMID- 24732616
TI  - Healed perivalvular abscess: Incidental finding on transesophageal
      echocardiography [corrected].
AB  - A 36-year-old male patient presented with the complaints of palpitations and
      breathlessness. Preoperative transthoracic echocardiography (TTE) revealed a
      bicuspid aortic valve; severe aortic regurgitation with dilated left ventricle
      (LV) and mild LV systolic dysfunction (ejection fraction 50%). He was scheduled
      to undergo aortic valve replacement. History was not suggestive of infective
      endocarditis (IE). Preoperative TTE did not demonstrate any aortic perivalvular
      abscess. Intraoperative transesophageal echocardiography (TEE) examination using
      the mid-esophageal (ME) long-axis view, showed an abscess cavity affecting the
      aortic valve, which initially was assumed to be a dissection flap, but later
      confirmed to be an abscess cavity by color Doppler examination. The ME aortic
      valve short-axis view showed two abscesses; one was at the junction of the non
      coronary and left coronary commissure and the other one above the right coronary
      cusp. Intraoperatively, these findings were confirmed by the surgeons. The case
      report demonstrates the superiority of TEE over TTE in diagnosing perivalvular
      abscesses. 

PMID- 24732617
TI  - Acute pulmonary embolism during an endoscopic retrograde
      cholangiopancreatography.
AB  - A 76-year-old female patient presented for an endoscopic retrograde
      cholangiopancreatography (ERCP) for the removal of a biliary stent and
      lithotripsy. During the procedure, an acute drop in the end-tidal CO 2 , followed
      by cardiovascular collapse prompted the initiation of the advanced cardiac life
      support protocol. Transesophageal echocardiography (TEE) demonstrated direct
      evidence of pulmonary embolism. The patient was promptly treated with
      thrombolytic therapy and subsequently discharged home on oral warfarin therapy,
      with no noted sequelae. Although, there have been case reports of air embolism
      during an ERCP presenting with cardiovascular collapse, to the best of our
      knowledge, there are no reported cases of acute pulmonary embolus during this
      procedure. While the availability of TEE in the operating suites is quite common,
      quick access and interpretation capabilities in remote locations may not be as
      common. With the expansion of anesthesia services outside of the operating rooms,
      it may be prudent to develop rapid response systems that incorporate resources
      such as TEE and trained personnel to deal with such emergent situations. 

PMID- 24732618
TI  - Left atrial ball thrombus with acute mesenteric ischemia: anesthetic management
      and role of transesophageal echocardiography.
AB  - A 62 year old female with severe mitral stenosis, large left atrial ball thrombus
      and acute mesenteric ischemia emergently underwent mitral valve replacement, left
      atrial clot removal and emergency laparotomy for mesenteric ischemia. Peri
      operative management issues, particularly, the anesthetic challenges and the role
      of transesophageal echocardiography are discussed. 

PMID- 24732619
TI  - Repair of recurrent pseudoaneurysm of the mitral-aortic intervalvular fibrosa:
      role of transesophageal echocardiography.
AB  - Pseudoaneurysm of mitral-aortic intervalvular fibrosa (P-MAIVF) is a rare cardiac
      surgical condition. P-MAIVF commonly occurs as a complication of aortic and
      mitral valve replacement surgeries. The surgical trauma during replacement of the
      valves weakens the avascular mitral and aortic intervalvular area. We present a
      case of P-MAIVF recurrence 5 years after a primary repair. Congestive cardiac
      failure was the presenting feature with mitral and aortic regurgitation. In view
      of the recurrence, the surgical team planned for a double valve replacement. The
      sewing rings of the two prosthetic-valves were interposed to close the mouth of
      the pseudoaneurysm and to provide mechanical reinforcement of the MAIVF. Intra
      operative transesophageal echocardiography (TEE) helped in delineating the
      anatomy, extent of the lesion, rupture of one of the pseudoaneurysm into left
      atrium and severity of the valvular regurgitation. Post-procedure TEE confirmed
      complete obliteration of the pseudoaneurysm and prosthetic valve function. 

PMID- 24732620
TI  - Aortic root to left-atrial fistula after aortic valve replacement: a rare
      complication and its intraoperative management.
AB  - Aorto-atrial fistula is a rare complication of prosthetic aortic valve
      replacement (AVR) and most of them have been diagnosed as a late complication. We
      present a case of this unusual complication after AVR. Intraoperative
      transoesophageal echocardiography identified and diagnosed this rare and
      potentially disastrous surgical complication and confirmed adequacy of its
      surgical repair. 

PMID- 24732621
TI  - Postoperative Takotsubo cardiomyopathy.
AB  - Takotsubo cardiomyopathy also known as transient apical ballooning syndrome or
      stress induced reversible cardiomyopathy is an increasingly reported syndrome
      generally characterized by transient systolic dysfunction of the apical and/or
      mid segment of the left ventricle. It is frequently precipitated by severe stress
      and clinically mimics an acute ST-elevation myocardial infarction, with
      angiographically normal coronary arteries. A high index of suspicion is needed to
      diagnose this syndrome. We describe a patient who developed Takotsubo
      cardiomyopathy in the post-operative period following vaginal hysterectomy. 

PMID- 24732622
TI  - Post extubation negative pressure pulmonary edema due to posterior mediastinal
      cyst in an infant.
AB  - A 3-month-old male child underwent uneventful inguinal herniotomy under general
      anesthesia. After extubation, airway obstruction followed by pulmonary edema
      appeared for which the baby was reintubated and ventilated. The baby made a
      complete recovery and extubated after about 2 h. A post-operative computed
      tomography scan revealed a posterior mediastinal cystic mass abutting the
      tracheal bifurcation. Presumably, extrinsic compression by the mass on the
      tracheal bifurcation led to the development of negative pressure pulmonary edema.

PMID- 24732623
TI  - A novel technique to prevent endobronchial spillage during video assisted
      thoracoscopic lobectomy.
AB  - Endobronchial spillage of fungal material into normal lung can infect it and the
      spillage of fungal material should be prevented during surgery. We report our
      experience of a patient who presented for right upper lobectomy with
      bronchiectasis, tubercular destruction and subsequent aspergilloma. A 4F Fogarty
      catheter was introduced through the tracheal lumen of the left sided
      endobronchial double lumen tube (DLT) to occlude the bronchus intermedius to
      prevent spillage of aspergilloma into the non-infected lower and middle lobes of
      the right lung. The Fogarty catheter was pulled into the trachea just before
      stapling the bronchus; thereafter, right upper lobectomy was completed
      successfully. The patient was extubated uneventfully and transferred to post
      operative recovery ward. The endobronchial blockage of the intermediate bronchus
      of the operative lung by the Fogarty catheter and isolation of the left lung by
      the DLT prevented spillage of aspergilloma in both the operative right lung and
      the left lung. 

PMID- 24732624
TI  - Use of nitric oxide in thoracic surgery for a high risk cardiac patient.
AB  - Nitric oxide (NO) is a selective pulmonary vasodilator especially in the presence
      of pulmonary artery hypertension. With right ventricle (RV) dysfunction, inhaled
      NO may increase RV ejection fraction and cardiac output. The main advantage of NO
      over intravenous therapy is its inability to decrease systemic pressure thereby
      maintaining the coronary perfusion pressure and the myocardial perfusion. In this
      case report, we discuss the use of NO in a routine thoracic surgery patient
      suffering with severe left ventricular dysfunction and a potential candidate for
      a very high cardiac risk. 

PMID- 24732625
TI  - Sotalol: a rescue drug in the face of life-threatening refractory ventricular
      tachycardia.
AB  - We describe postoperative refractory ventricular tachycardia (VT) in a patient
      following aortic and mitral valve replacement. Following an uneventful separation
      from cardiopulmonary bypass with dobutamine, the patient developed recurrent VT,
      4 hours into the postoperative period. The VT did not respond to standard doses
      of xylocard, magnesium and amiodarone. Electrolyte and acid base parameters were
      normal. Multiple cardioversions failed to revert back to a stable rhythm. Intra
      aortic balloon pumping was instituted and overdrive right ventricular pacing was
      unsuccessful. Following intravenous sotalol 80 mg, the VT came under control and
      reverted to a nodal rhythm, which required atrial pacing for the next 8 hours.
      Oral sotalol therapy was continued at 40 mg daily. The VT did not recur. 

PMID- 24732626
TI  - Angioedema due to the new oral anticoagulant rivaroxaban.

PMID- 24732627
TI  - Extracorporeal membrane oxygenator for atrial septal defect!!

PMID- 24732628
TI  - Labor analgesia in Eisenmenger syndrome: peripartum concerns.

PMID- 24732629
TI  - Plasma vitamin D and prostate cancer risk: results from the Selenium and Vitamin
      E Cancer Prevention Trial.
AB  - BACKGROUND: In vitro, animal, and ecological studies suggest that inadequate
      vitamin D intake could increase prostate cancer risk, but results of biomarker
      based longitudinal studies are inconsistent. METHODS: Data for this case (n =
      1,731) and cohort (n = 3,203) analysis are from the Selenium and Vitamin E Cancer
      Prevention Trial. Cox proportional hazard models were used to test whether
      baseline plasma vitamin D (25-hydroxy) concentration, adjusted for season of
      blood collection, was associated with the risk of total and Gleason score 2-6, 7
      10, and 8-10 prostate cancer. RESULTS: There were U-shaped associations of
      vitamin D with total cancer risk: compared with the first quintile, HRs were 0.83
      [95% confidence interval (CI), 0.66-1.03; P = 0.092], 0.74 (95% CI, 0.59-0.92; P
      = 0.008), 0.86 (95% CI, 0.69-1.07; P = 0.181), and 0.98 (95% CI, 0.78-1.21; P =
      0.823), for the second through fifth quintiles, respectively. For Gleason 7-10
      cancer, corresponding HRs were 0.63 (95% CI, 0.45-0.90; P = 0.010), 0.66 (95% CI,
      0.47-0.92; P = 0.016), 0.79 (95% CI, 0.56-1.10; P = 0.165), and 0.88 (95% CI,
      0.63-1.22; P = 0.436). Among African American men (n = 250 cases), higher vitamin
      D was associated with reduced risk of Gleason 7-10 cancer only: in the a
      posteriori contrast of quintiles 1-2 versus 3-5, the HR was 0.55 (95% CI, 0.31
      0.97; P = 0.037), with no evidence of dose-response or a U-shaped association.
      CONCLUSIONS: Both low and high vitamin D concentrations were associated with
      increased risk of prostate cancer, and more strongly for high-grade disease.
      IMPACT: The optimal range of circulating vitamin D for prostate cancer prevention
      may be narrow. Supplementation of men with adequate levels may be harmful. Cancer
      Epidemiol Biomarkers Prev; 23(8); 1494-504. (c)2014 AACR.

PMID- 24732630
TI  - Physicians, clinics, and neighborhoods: multiple levels of influence on
      colorectal cancer screening.
AB  - BACKGROUND: We (i) described variability in colorectal cancer (CRC) test use
      across multiple levels, including physician, clinic, and neighborhood; and (ii)
      compared the performance of novel cross-classified models versus traditional
      hierarchical models. METHODS: We examined multilevel variation in CRC test use
      among patients not up-to-date with screening in a large, urban safety net health
      system (2011-2012). Outcomes included: (i) fecal occult blood test (FOBT) or (ii)
      colonoscopy and were ascertained using claims data during a 1-year follow-up. We
      compared Bayesian (i) cross-classified four-level logistic models nesting
      patients within separate, nonoverlapping "levels" (physicians, clinics, and
      census tracts) versus (ii) three hierarchical two-level models using deviance
      information criterion. Models were adjusted for covariates (patient
      sociodemographic factors, driving time to clinic, and census tract poverty rate).
      RESULTS: Of 3,195 patients, 157 (4.9%) completed FOBT and 292 (9.1%) completed
      colonoscopy during the study year. Patients attended 19 clinics, saw 177
      physicians, and resided in 332 census tracts. Significant variability was
      observed across all levels in both hierarchical and cross-classified models that
      was unexplained by measured covariates. For colonoscopy, variance was similar
      across all levels. For FOBT, physicians, followed by clinics, demonstrated the
      largest variability. Model fit using cross-classified models was superior or
      similar to 2-level hierarchical models. CONCLUSIONS: Significant and substantial
      variability was observed across neighborhood, physician, and clinic levels in CRC
      test use, suggesting the importance of factors at each of these levels on CRC
      testing. IMPACT: Future multilevel research and intervention should consider the
      simultaneous influences of multiple levels, including clinic, physician, and
      neighborhood.

PMID- 24732631
TI  - Green preparation of reduced graphene oxide for sensing and energy storage
      applications.
AB  - Preparation of graphene from chemical reduction of graphene oxide (GO) is
      recognized as one of the most promising methods for large-scale and low-cost
      production of graphene-based materials. This study reports a new, green, and
      efficient reducing agent (caffeic acid/CA) for GO reduction. The CA-reduced GO
      (CA-rGO) shows a high C/O ratio (7.15) that is among the best rGOs prepared with
      green reducing reagents. Electronic gas sensors and supercapacitors have been
      fabricated with the CA-rGO and show good performance, which demonstrates the
      potential of CA-rGO for sensing and energy storage applications. 

PMID- 24732632
TI  - Dense neuron clustering explains connectivity statistics in cortical
      microcircuits.
AB  - Local cortical circuits appear highly non-random, but the underlying connectivity
      rule remains elusive. Here, we analyze experimental data observed in layer 5 of
      rat neocortex and suggest a model for connectivity from which emerge essential
      observed non-random features of both wiring and weighting. These features include
      lognormal distributions of synaptic connection strength, anatomical clustering,
      and strong correlations between clustering and connection strength. Our model
      predicts that cortical microcircuits contain large groups of densely connected
      neurons which we call clusters. We show that such a cluster contains about one
      fifth of all excitatory neurons of a circuit which are very densely connected
      with stronger than average synapses. We demonstrate that such clustering plays an
      important role in the network dynamics, namely, it creates bistable neural
      spiking in small cortical circuits. Furthermore, introducing local clustering in
      large-scale networks leads to the emergence of various patterns of persistent
      local activity in an ongoing network activity. Thus, our results may bridge a gap
      between anatomical structure and persistent activity observed during working
      memory and other cognitive processes. 

PMID- 24732633
TI  - Gemcitabine-induced pancreatic cancer cell death is associated with
      MST1/cyclophilin D mitochondrial complexation.
AB  - The pancreatic adenocarcinoma remains the most aggressive human malignancy with
      an extremely low 5-year overall survival. Postoperative gemcitabine could
      significantly delay recurrence after complete resection of pancreatic cancer.
      However, the underlying mechanisms are not fully understood. The chemo-resistance
      factors against gemcitabine still need further characterizations. Here we studied
      the mechanism of gemcitabine-induced pancreatic cancer cell death by focusing on
      mammalian sterile 20-like kinase 1 (MST1) and cyclophilin D (Cyp-D). We found
      that MST1 and Cyp-D expressions were significantly lower in gemcitabine-resistant
      pancreatic cancer tissues and cell lines. In vitro, gemcitabine activated MST1
      through reactive oxygen species (ROS) production, which was prevented by
      antioxidant n-acetyl-cysteine (NAC). We found that gemcitabine-activated MST1
      translocated to mitochondria and formed a complex with the local protein Cyp-D.
      Gemcitabine-induced cell death was alleviated by MST1 or Cyp-D shRNA silencing,
      but was aggravated by MST1 or Cyp-D over-expression. Further, cyclosporin A
      (CsA), the Cyp-D inhibitor, prevented gemcitabine-induced MST1/Cyp-D
      mitochondrial complexation and cancer cell death. We suggest that gemcitabine
      induced death of pancreatic cancer cells requires MST1/Cyp-D mitochondrial
      complexation.

PMID- 24732635
TI  - Biodegradable Fe-based alloys for use in osteosynthesis: outcome of an in vivo
      study after 52 weeks.
AB  - This study investigates the degradation performance of three Fe-based materials
      in a growing rat skeleton over a period of 1 year. Pins of pure Fe and two Fe
      based alloys (Fe-10 Mn-1Pd and Fe-21 Mn-0.7C-1Pd, in wt.%) were implanted
      transcortically into the femur of 38 Sprague-Dawley rats and inspected after 4,
      12, 24 and 52 weeks. The assessment was performed by ex vivo microfocus computed
      tomography, weight-loss determination, surface analysis of the explanted pins and
      histological examination. The materials investigated showed signs of degradation;
      however, the degradation proceeded rather slowly and no significant differences
      between the materials were detected. We discuss these unexpected findings on the
      basis of fundamental considerations regarding iron corrosion. Dense layers of
      degradation products were formed on the implants' surfaces, and act as barriers
      against oxygen transport. For the degradation of iron, however, the presence of
      oxygen is an indispensable prerequisite. Its availability is generally a critical
      factor in bony tissue and rather limited there, i.e. in the vicinity of our
      implants. Because of the relatively slow degradation of both pure Fe and the Fe
      based alloys, their suitability for bulk temporary implants such as those in
      osteosynthesis applications appears questionable.

PMID- 24732634
TI  - A multifunctional streptococcal collagen-mimetic protein coating prevents
      bacterial adhesion and promotes osteoid formation on titanium.
AB  - The major barriers to the clinical success of orthopedic and dental implants are
      poor integration of fixtures with bone tissue and biomaterial-associated
      infections. Although multifunctional device coatings have long been considered a
      promising strategy, their development is hindered by difficulties in integrating
      biocompatibility, anti-infective activity and antithrombotic properties within a
      single grafting agent. In this study, we used cell adhesion assays and confocal
      microscopy of primary murine osteoblasts and human osteoblast cell lines MG-63
      and Saos-2 to demonstrate that a streptococcal collagen-like protein engineered
      to display the alpha1 and alpha2 integrin recognition sequences enhances
      osteoblast adhesion and spreading on titanium fixtures. By measuring calcium
      deposition and alkaline phosphatase activity, we also showed that selective
      activation of alpha2beta1 integrin induces osteoblast differentiation, osteoid
      formation and mineralization. Moreover, cell adhesion assays and scanning
      electron microscopy of clinical isolates Staphylococcus aureus Philips and
      Staphylococcus epidermidis 9491 indicated that streptococcal collagen-mimetic
      proteins inhibit bacterial colonization and biofilm formation irrespective of
      their interaction with integrins. Given that streptococcal collagenous substrates
      neither interact with platelets nor trigger a strong immune response, this novel
      bioactive coating appears to have desirable multifaceted properties with
      promising translational applications. 

PMID- 24732636
TI  - Effects of (+)-8-OH-DPAT on the duration of immobility during the forced swim
      test and hippocampal cell proliferation in ACTH-treated rats.
AB  - In the present study, we examined the effect of ACTH on the immobilization of
      rats in the forced swim test and hippocampal cell proliferation after
      administration of the 5-HT1A receptor agonist, R-(+)-8-hydroxy-2-di-n-propylamino
      tetralin ((+)-8-OH-DPAT). Chronic treatment with (+)-8-OH-DPAT (0.01-0.1 mg/kg,
      s.c.) significantly decreased the duration of immobility in saline- and ACTH
      treated rats. Chronic administration of ACTH caused a significant decrease in
      hippocampal cell proliferation. However, (+)-8-OH-DPAT significantly normalized
      cell proliferation in ACTH-treated rats. We then investigated the effects of (+)
      8-OH-DPAT on the expression of brain-derived neurotrophic factor (BDNF) and
      cyclin D1 (elements of cyclic adenosine monophosphate response element-binding
      protein (CREB)-BDNF and Wnt signaling pathways, respectively) in the hippocampus
      of saline- and ACTH-treated rats. ACTH treatment significantly decreased the
      expression of cyclin D1, while treatment with (+)-8-OH-DPAT normalized the
      expression of cyclin D1 in ACTH-treated rats. However, the expression of BDNF did
      not change in either saline- or ACTH-treated rats. These findings suggest that
      the antidepressant effects of (+)-8-OH-DPAT in treatment-resistant animals may be
      attributed to an enhancement of hippocampal cell proliferation, at least in part
      due to an enhancement of cyclin D1 expression.

PMID- 24732637
TI  - Acute effects on brain cholecystokinin-like concentration and anxiety-like
      behaviour in the female rat upon a single injection of 17beta-estradiol.
AB  - BACKGROUND: The neuropeptide cholecystokinin (CCK) has been implicated in the
      neurobiology of anxiety and panic disorders, as well as in dopamine-related
      behaviours. Anxiety and panic-disorders are twice as common in females compared
      to males, but studies of females are rare, although increasing in number. Limited
      studies have found that CCK fluctuates in limbic regions during the estrous
      cycle, and that CCK and its receptors are sensitive to estrogen. AIM/PURPOSE: The
      aim of the present work was to study the acute effects of 17beta-estradiol on
      anxiety-like behaviour and on CCK-like immunoreactivity (LI) in the female rat
      brain (amygdala, hippocampus, nucleus accumbens, and cingulate cortex). METHODS:
      Four groups of female Sprague-Dawley rats were used: ovariectomized,
      ovariectomized+17beta-estradiol-replacement, sham, and sham+17beta-estradiol
      replacement. The effect of 17beta-estradiol-replacement on anxiety-related
      behaviour was measured in all animals on the elevated plus maze 2-24 h after
      injection. CCK-LI concentration was measured in punch biopsies by means of
      radioimmunoassay. RESULTS: 17beta-estradiol decreased anxiety-like behaviour 2 h
      after administration in ovariectomized and sham-operated animals, as demonstrated
      by increased exploration of the open arms compared to respective sesame oil
      treated controls. This effect was not present when testing occurred 24 h post
      treatment. The rapid behavioural effect of 17beta-estradiol was accompanied by
      changes in CCK-LI concentrations in regions of the limbic system including
      cingulate cortex, hippocampus, amygdala and nucleus accumbens. CONCLUSION:
      Although the interpretation of these data requires caution since the data were
      collected from two different experiments, our results suggest that estrogen
      induced anxiolytic effects may be associated with changes of the CCK-system in
      brain regions controlling anxiety-like behaviour.

PMID- 24732638
TI  - Tau-based therapeutic approaches for Alzheimer's disease - a mini-review.
AB  - The accumulation of aggregated, hyperphosphorylated tau as neurofibrillary
      tangles and neuropil threads are cardinal features of Alzheimer's disease (AD).
      The other lesions found in AD include amyloid plaques and congophilic amyloid
      angiopathy, both associated with the extracellular accumulation of the amyloid
      beta (Abeta) peptide. AD is the most common cause of dementia globally.
      Currently, there are no effective means to treat AD or even to slow it down. The
      dominant theory for the causation of AD is the amyloid cascade hypothesis, which
      suggests that the aggregation of Abeta as oligomers and amyloid plaques is
      central to the pathogenesis of AD. Numerous therapies have been developed
      directed to Abeta-related pathology, in particular various immunotherapeutic
      approaches. So far all of these have failed in clinical trials. Recently, there
      has been more focus on therapy directed to tau-related pathology, which
      correlates better with the cognitive status of patients, compared to the amyloid
      burden. Immunotherapeutic targeting of tau pathology has shown great potential in
      treating tau pathologies in mouse models of AD. A number of studies have shown
      the efficacy of both passive and active immunization. This review summarizes
      recent advances in therapy targeting pathological tau protein, in particular
      focusing on immunotherapeutic approaches which are showing great promise.

PMID- 24732639
TI  - Glutathione S-transferase T1 and M1 polymorphisms are associated with lung cancer
      risk in a gender-specific manner.
AB  - BACKGROUND: Glutathione S-transferase (GST) T1 and M1 are detoxification enzymes
      which neutralize various carcinogenic compounds. Polymorphisms of the GSTT1 and
      GSTM1 genes which encode the enzymes could be associated with cancer risk.
      PATIENTS AND METHODS: We investigated the association of GSTT1 and GSTM1 null
      polymorphisms with lung cancer risk in a tightly matched, considerably large
      sample in China. Genotyping was performed utilizing polymerase chain reaction
      restriction fragment length polymorphism (PCR-RFLP) analysis and DNA sequencing,
      and associations were measured by using logistic regression analysis. RESULTS: We
      found that the null genotypes of both polymorphisms resulted in an increased lung
      cancer risk, with an odds ratio (OR) of 1.57 (95% confidence interval (CI) 1.23
      2.00) for GSTT1 and OR 1.87 (95% CI 1.46-2.39) for GSTM1 (p < 0.01). Significant
      associations remained after stratification by histopathology (p < 0.01) and
      smoking status (p < 0.05). When gender-stratified association was performed, we
      found that the GSTT1 null genotype resulted in an increased risk among males
      (adjusted OR 2.95, 95% CI 2.07-4.20; p < 0.01) but not females (p > 0.05), while
      the GSTM1 null genotype resulted in an increased risk among females (adjusted OR
      2.18, 95% CI 1.54-3.10; p < 0.01) but not males (p < 0.05). CONCLUSION:
      Polymorphisms in GSTT1 and GSTM1 are associated with the risk of lung cancer in a
      gender-specific manner.

PMID- 24732640
TI  - Intermittent pneumatic compression pump for breast cancer-related lymphedema: a
      systematic review and meta-analysis of randomized controlled trials.
AB  - BACKGROUND: Breast cancer-related lymphedema (BCRL) is a common complication
      after the treatment of breast cancer. The objective of this study was to
      determine whether the use of an intermittent pneumatic pump (IPC) could manage
      lymphedema effectively. METHODS: We searched PubMed, EMBASE, and the Cochrane
      Library for related trials to compare the percent of volume reduction and
      subjective symptoms. RESULTS: 7 randomized controlled trials, with 287 patients,
      were included. Results showed that the use of the IPC could alleviate lymphedema,
      but no significant difference between routine management of lymphedema with or
      without pneumatic pump existed. CONCLUSION: Current trials fail to show the
      effectiveness of the addition of an IPC to the routine management of BCRL.

PMID- 24732641
TI  - MDM2 rs2279744 and TP53 rs1042522 polymorphisms associated with etoposide- and
      cisplatin-induced grade III/IV neutropenia in Chinese extensive-stage small-cell
      lung cancer patients.
AB  - BACKGROUND/AIMS: Etoposide and cisplatin (EP) chemotherapy is the most frequently
      used regimen in extensive-stage small-cell lung cancer (SCLC) patients, although
      the side effects (e.g., neutropenia) are high. This study investigates the
      association of the MDM2 rs2279744 and TP53 rs1042522 single-nucleotide
      polymorphisms (SNPs) with EP-induced grade III/IV neutropenia and with response
      to EP in extensive-stage SCLC patients. METHODS: Blood samples from 119 extensive
      stage SCLC patients were subjected to genotyping of these 2 SNPs, using the
      allele-specific matrix-assisted laser desorption ionization-time-of-flight (MALDI
      TOF) mass spectrometry for determining the association with neutropenia in the
      patients. RESULTS: The data showed that patients carrying the MDM2 rs2279744-GG
      genotype were associated with a lower incidence of grade III/IV neutropenia in
      the recessive and additive models, while the TP53 rs1042522-CC genotype was
      associated with a higher incidence in the recessive model. Furthermore, the
      combination of the MDM2 rs2279744-TT+TG and the TP53 rs1042522-CC genotype was
      associated with a significantly higher incidence of grade III/IV neutropenia. And
      the combination of the MDM2 rs2279744-GG and the TP53 rs1042522-GG+GC genotype
      was associated with the lowest incidence of grade III/IV neutropenia.
      CONCLUSIONS: MDM2 rs2279744 and TP53 rs1042522 SNPs were associated with EP
      induced high-grade neutropenia in extensive-stage SCLC patients. Further studies
      are needed to investigate the underlying mechanisms.

PMID- 24732642
TI  - Clinicopathologic significance of nuclear factor-kappaB and vascular endothelial
      growth factor expression in advanced gastric cancer patients.
AB  - BACKGROUND: Nuclear factor-kappaB (NF-kappaB) and vascular endothelial growth
      factor (VEGF) are involved in cell proliferation, invasion, angiogenesis, and
      metastasis. The principal objective of this study was to assess the prognostic
      significance of NF-kappaB and VEGF expression in gastric cancer. METHODS: Tumor
      tissues of 154 patients with gastric cancer, all of whom underwent potentially
      curative resection, were immunohistochemically evaluated using monoclonal
      antibodies against NF-kappaB and VEGF. RESULTS: The positivity rates of NF-kappaB
      and VEGF staining were 44.2% and 39.6%, respectively. NF-kappaB expression in
      tumor tissues was significantly correlated with VEGF expression (p < 0.001). VEGF
      expression was related to Lauren's classification (p = 0.002), differentiation (p
      = 0.043), depth of invasion (p = 0.005), carcinoembryonic antigen expression (p =
      0.032), and stage (p = 0.026). Univariate analysis demonstrated that NF-kappaB
      expression was significantly related to both the 5-year disease-free survival
      (65.2% vs. 46.4%, p = 0.007) and the 5-year overall survival (60.0% vs. 42.5%, p
      = 0.014). Multivariate analysis verified that NF-kappaB was independently
      associated with disease-free survival (hazard ratio: 2.082, p = 0.005) and
      overall survival (hazard ratio: 1.841, p = 0.008). CONCLUSION: NF-kappaB
      expression in tumor tissue is associated with poor survival in gastric cancer
      patients.

PMID- 24732643
TI  - The Glasgow Prognostic Score is an independent prognostic predictor of
      hepatocellular carcinoma following radical resection.
AB  - BACKGROUND: Some prognostic evaluation systems were developed to postoperatively
      predict the outcome of hepatocellular carcinoma (HCC) patients, mainly based on
      the cancer itself and the underlying liver diseases. However, none of these
      prognostic evaluation systems have so far been universally accepted. A simple and
      feasible scoring system is still lacking for the prediction of prognosis of HCC
      patients following resection. We aimed to uncover the correlation between the
      preoperative Glasgow Prognostic Score (GPS) and the clinical outcome of HCC
      patients after radical resection. METHODS: The patients were separated into 3
      subgroups on the basis of their GPSs. The prognostic significance of the GPS in
      the patient cohort was evaluated by survival analysis. RESULTS: On univariate
      analysis, the levels of C-reactive protein and albumin, the Child-Pugh class,
      vascular invasion, tumor number, tumor size, the tumor/node/metastasis (TNM)
      stage, and the GPS were associated with overall survival and time to recurrence
      of HCC patients after radical resection. On multivariate analysis, the tumor
      size, albumin level, and GPS were independently associated with the outcome of
      HCC postoperatively. CONCLUSION: The GPS is an independent biomarker for
      prognostic prediction of HCC following radical resection.

PMID- 24732644
TI  - Expression of eukaryotic initiation factor 3f is associated with prognosis in
      gastric carcinomas.
AB  - BACKGROUND: Eukaryotic initiation factor 3f (eIF3f) expression, which plays an
      important role in human cancer, is significantly decreased in various types of
      cancers. The aim of this study was to detect the expression of eIF3f in gastric
      carcinoma (GC), which until now has not been reported. METHODS: Expression of
      eIF3f was detected by immunohistochemistry in GC tissues and adjacent non
      cancerous tissues (ANCT) from 195 patients with stage I-III GC who underwent
      curative gastrectomy. Clinicopathological results, including survival, were
      analyzed. RESULTS: Expression rate of eIF3f in GC and ANCT were 44.8 and 81.7%
      respectively. Low expression of eIF3f was significantly associated with an
      increased serum level of carcinoma embryonic antigen (p = 0.02), but not with
      levels of carbohydrate antigen 19-9 (p = 0.29). eIF3f levels were linked to more
      advanced tumor stages and likelihood of recurrence (all p < 0.05).The Kaplan
      Meier survival curves indicated that decreased expression of eIF3f was a
      significant factor for a poor prognosis for GC patients (p = 0.04). CONCLUSION:
      eIF3f may play an important role in recurrence. Its function and potential as a
      prognostic marker should be further verified in GC.

PMID- 24732645
TI  - Evaluation of factors associated with pain experienced during mammary ductoscopy.
AB  - BACKGROUND: The aim of this study was to evaluate patient characteristics and
      findings after mammary ductoscopy in an effort to reduce the pain experienced
      during the procedure. PATIENTS AND METHODS: We evaluated outpatients in whom
      mammary ductoscopy was performed under local or intraductal anesthesia without
      preference, and their clinical characteristics and findings were recorded.
      Average and maximum pain scores were determined after the examination for
      statistical analysis. RESULTS: The overall average pain score was 3.74 +/- 1.353,
      and the maximum pain score was 6.40 +/- 1.681. The type of anesthesia, total
      operation time, nipple retraction, and discharge status significantly correlated
      with the pain score. Intraductal anesthesia lowered the average pain score by
      0.60, whereas a total procedure time greater than 12 min increased the average
      pain score by 0.956. The pain score decreased if patients had nipple retraction,
      and intraductal anesthesia proved suitable for patients with normal nipples.
      CONCLUSION: Intraductal anesthesia is suitable for most patients, and ductoscopy
      should not exceed 12 min to minimize the pain. Nipple retraction does not
      significantly increase pain, but local anesthesia should be used in patients with
      retracted nipples. Patient age, breastfeeding history, menstrual stage, and
      presence of intraductal tumors were not associated with the level of pain
      experienced.

PMID- 24732646
TI  - Neuropathological characteristics of progression after prolonged response to
      bevacizumab in multifocal hemangioblastoma.
AB  - BACKGROUND: Antiangiogenic treatment has been explored in few patients with
      hemangioblastoma after failure of surgery and radiotherapy. CASE REPORT: We
      present the first histopathological follow-up study of a bevacizumab-responsive
      hemangioblastoma that eventually progressed. For a period of 12 months, therapy
      with bevacizumab achieved a clinical response and radiological stabilization in a
      patient with progressive multifocal central nervous system (CNS)
      hemangioblastoma. Subsequently, selected tumor sites showed radiological
      progression, in particular, the formation of an intramedullary lesion of the
      initially predominantly leptomeningeal disease. Histology showed diffuse dural
      invasion by the hemangioblastoma accompanied with a relatively reduced cell
      density compared to the preserved vessel structures. CONCLUSION: The pattern of
      progression upon vascular endothelial growth factor (VEGF)-targeting
      antiangiogenic treatment in hemangioblastoma may involve increased tumor
      invasiveness.

PMID- 24732647
TI  - Frequency and severity of semantic deficits in a consecutive memory clinic
      cohort.
AB  - BACKGROUND/AIM: Semantic memory deficits have been shown in dementia and mild
      cognitive impairment (MCI) by group comparisons. The aim of this study is to
      investigate the frequency of impairments on tests with semantic content in
      patients with dementia, MCI (amnestic and non-amnestic) and affective disorders.
      METHODS: A Famous faces test, Boston Naming Test and Category fluency were
      applied in 114 consecutive memory clinic patients and 95 healthy participants
      (all participants were 60 years old or older; dementia/MCI patients had Mini
      Mental State Examination scores >=20). RESULTS: Fifty-three patients were
      classified with dementia, 36 with MCI (14 amnestic, 22 non-amnestic) and 25 with
      affective disorders. Dementia and MCI patients differed significantly from the
      control group on all tests. Patients with dementia and MCI had impairments in
      about 40% of the cases (on the most sensitive tests). However, patients with
      affective disorders also had mild impairments on tests tapping semantic memory
      (25% were impaired on the most sensitive tests). Impairments on the Famous faces
      test were more frequently found in dementia and MCI as compared to patients with
      affective disorders. CONCLUSION: Short tests with semantic memory content are
      sensitive to changes in dementia and MCI, but impairments on such tests may also
      be found in other diseases, e.g. affective disorders.

PMID- 24732648
TI  - Monochromatic ultra-slow (~0.1 Hz) oscillations in the human electroencephalogram
      and their relation to hemodynamics.
AB  - Previous studies demonstrated the presence of Monochromatic Ultra-Slow
      Oscillations (MUSO) in human EEG. In the present study we explored the biological
      origin of MUSO by simultaneous recordings of EEG, Near-Infrared Spectroscopy
      (NIRS), arterial blood pressure, respiration and Laser Doppler flowmetry. We used
      a head-up tilt test in order to check whether MUSO might relate to Mayer waves in
      arterial blood pressure, known to be enhanced by the tilting procedure. MUSO were
      detected in 8 out of 10 subjects during rest and showed a striking monochromatic
      spectrum (0.07-0.14 Hz). The spatial topography of MUSO was complex, showing
      multiple foci variable across subjects. While the head-up tilt test increased the
      relative power of Mayer waves, it had no effect on MUSO. On the other hand, the
      relative spectral power of 0.1 Hz oscillations in EEG, NIRS and blood pressure
      signals were positively correlated across subjects in the tilted condition. Eight
      subjects showed a coherence between MUSO and NIRS/arterial blood pressure.
      Moreover, MUSO at different electrode sites demonstrated coherence not reducible
      to volume conduction, thus indicating that MUSO are unlikely to be generated by
      one source. We related our experimental findings to known biological phenomena
      being generated at about 0.1 Hz, i.e.: arterial blood pressure, cerebral and skin
      vasomotion, respiration and neuronal activity. While no definite conclusion can
      yet be drawn as to an exact physiological mechanism of MUSO, we suggest that
      these oscillations might be of a rather extraneuronal origin reflecting cerebral
      vasomotion.

PMID- 24732649
TI  - Comparison of two nasoalveolar molding techniques in unilateral complete cleft
      lip patients: a randomized, prospective, single-blind trial to compare nasal
      outcomes.
AB  - BACKGROUND: Nasoalveolar molding became increasingly popular in the 1990s as a
      means of easing surgery and improving nasal outcomes for cleft lip repairs. In
      the late 1990s, three orthodontists from our center underwent nasoalveolar
      molding training: two at the Rush Craniofacial Center, in Chicago; and one at New
      York University Craniofacial Center. They brought two different nasoalveolar
      molding techniques back to Chang Gung Craniofacial Center: the modified Figueroa
      and the modified Grayson techniques. Outcomes following use of these techniques
      have not previously been compared prospectively. METHODS: Between May of 2010 and
      March of 2013, a randomized, prospective, single-blind trial was conducted to
      compare the number of clinical visits, total costs, complications, and nasal
      symmetry between the two nasoalveolar molding techniques in 30 patients with
      unilateral complete cleft lip. RESULTS: There were no differences between
      nasoalveolar molding techniques in the number of clinical visits, total costs,
      nostril height, or nostril area ratio. Preoperatively but after nasoalveolar
      molding, the nostril width ratio was wider for the Figueroa group than for the
      Grayson group. Six months after surgical correction, there were no differences in
      nostril height, nostril width, nasal sill height, or nostril area ratio between
      nasoalveolar molding methods. Alveolar ulceration occurred more frequently in the
      Grayson group. CONCLUSIONS: The modified Grayson technique reduced nostril width
      more efficiently, but alveolar ulceration was more frequent and no differences in
      nostril width were found following surgery. Overall, the two nasoalveolar molding
      techniques produced similar nasal outcomes. CLINICAL QUESTION/LEVEL OF EVIDENCE:
      Therapeutic, II.

PMID- 24732650
TI  - A systematic review of functional donor-site morbidity after latissimus dorsi
      muscle transfer.
AB  - BACKGROUND: The authors performed a comprehensive literature review regarding
      functional impairment after latissimus dorsi muscle transfer, to investigate
      functional changes in the donor site and the potential impact on patients' daily
      lives. METHODS: The PubMed database was searched for articles regarding
      functional donor-site morbidity following latissimus dorsi muscle flap harvest.
      Articles discussing the thoracodorsal artery perforator flap, which shares the
      same donor sites with the latissimus dorsi muscle flap, were also included.
      Functional morbidity was analyzed based on questionnaire of subjective symptoms,
      Disabilities of the Arm, Shoulder and Hand questionnaire, shoulder range of
      motion, and shoulder strength. RESULTS: Twenty-two articles representing 719
      cases in 644 patients were reviewed, including seven prospective and 15
      retrospective cohort studies. As a questionnaire summary from eight articles, 94
      of 232 patients (41 percent) experienced any kind of discomfort at the donor
      site. In the Disabilities of the Arm, Shoulder and Hand questionnaire from seven
      articles, little difficulty in daily activities but significant difficulties in
      sports and art activities were observed. Nine of 13 articles reported some
      limitations of shoulder motion, particularly during the early postoperative
      period, and four other articles detected little limitation. Eight of 12 articles
      reported some shoulder strength weakness over time, and shoulder extension,
      adduction, and internal rotation were commonly involved. The muscle-sparing
      latissimus dorsi and thoracodorsal artery perforator flaps showed low functional
      morbidity. CONCLUSIONS: Functional impairment of the shoulder could develop after
      latissimus dorsi muscle flap transfer. Knowledge of the flap's functional
      morbidity will allow surgeons to inform patients regarding donor-site
      expectations and to accomplish better surgical outcomes.

PMID- 24732651
TI  - Value of surgical decompression of compressed nerves in the lower extremity in
      patients with painful diabetic neuropathy: a randomized controlled trial.
AB  - BACKGROUND: The authors aimed to assess the effect of lower extremity nerve
      decompression surgery for painful diabetic polyneuropathy on pain and
      sensibility. METHODS: The study was conducted as a single-center randomized
      controlled trial of one intervention with 1-year follow-up. Forty-two patients
      with painful diabetic neuropathy were included. After randomization, the lower
      extremity nerves were decompressed at four sites in one limb. The contralateral
      limb was used as control (within-patient comparison). All patients were assessed
      preoperatively and at 3, 6, and 12 months postoperatively. Primary outcome was
      the visual analogue scale score 12 months after surgery. Secondary outcomes were
      Semmes Weinstein monofilament testing and two-point discrimination outcomes at 3,
      6, and 12 months. RESULTS: Visual analogue scale scores improved significantly
      from a mean of 6.1 (95 percent CI, 5.5 to 6.7) preoperatively to 3.5 (95 percent
      CI, 2.5 to 4.4) at 12 months postoperatively (p<0.001). The score was also
      significantly lower compared with the control leg score of 5.3 (95 percent CI,
      4.4 to 6.2; p<0.001) at 12 months. Overall, 73.7 percent of the patients improved
      their score on the visual analogue scale, of which 35.7 percent had a decrease of
      more than five points. CONCLUSION: Surgical decompression of the nerves of the
      lower extremity can be added as a therapeutic option for patients with painful
      diabetic neuropathy who show signs of chronic nerve compression by means of a
      positive Tinel or other diagnostic criteria, when pain medication fails to reduce
      pain to an acceptable standard. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic,
      I.

PMID- 24732652
TI  - Impact of total skin-sparing mastectomy incision type on reconstructive
      complications following radiation therapy.
AB  - BACKGROUND: Postoperative complications after total skin-sparing mastectomy and
      expander-implant reconstruction can negatively impact outcomes, particularly in
      the setting of postmastectomy radiation therapy. The authors studied whether
      rates of ischemic complications after postmastectomy radiation therapy are
      impacted by the total skin-sparing mastectomy incision. METHODS: The authors
      queried a prospectively collected database of patients undergoing total skin
      sparing mastectomy and immediate two-stage expander-implant reconstruction. Their
      hypothesis was that, in the setting of radiation therapy, patients with
      inframammary incisions would be more likely to develop ischemic complications
      than those without incisions on the dependent portion of the breast. We divided
      our patient cohort into two groups, those with inframammary incisions and those
      with other incisions, and then analyzed the proportion that received radiation
      therapy. RESULTS: Of 756 cases included in the analysis, 91 (12 percent) received
      postmastectomy radiation therapy, 62 (68.1 percent) with inframammary incisions
      and 29 (31.9 percent) with other incisions. Mean follow-up was 3.1 years. Rates
      of mastectomy skin flap necrosis (3.2 percent versus 6.9 percent, p=0.4)
      following radiation therapy were not significantly higher in the inframammary
      group. However, breakdown of the total skin-sparing mastectomy incision was twice
      as likely in the inframammary group (21 percent versus 10.3 percent, p=0.2) and
      was more likely to lead to subsequent implant removal when incisional breakdown
      occurred (77 percent versus 0 percent, p=0.03). CONCLUSIONS: Total skin-sparing
      mastectomy incision type may impact rates of incisional breakdown and implant
      loss following postmastectomy radiation therapy, with higher rates seen with
      inframammary incisions. Multiple factors, including breast size, breast ptosis,
      and likelihood of radiation therapy, should be considered in determining optimal
      incision. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

PMID- 24732653
TI  - The effect of platelet-rich plasma on composite graft survival.
AB  - BACKGROUND: Composite grafts are suitable for facial reconstruction because of
      good color matching, low donor-site morbidity, acceptable texture, and easy
      surgical techniques. However, their use is limited to small defects and by
      unpredictable survival rates. As platelet-rich plasma contains large numbers of
      growth factors and has been widely used for tissue regeneration, this study aimed
      to investigate platelet-rich plasma as an adjuvant to enhance composite graft
      survival. METHODS: Twenty New Zealand White rabbits were used, and
      chondrocutaneous composite grafts were applied to their ears. The grafts were
      then returned to their original positions after rotation to block the original
      circulation from the base of the graft. Each of the individual ears was assigned
      randomly into one of two groups: experimental (n=20; platelet-rich plasma group)
      or control (n=20; control group). The surrounding skin of the composite graft was
      injected with either 1.0 ml of platelet-rich plasma derived from autologous whole
      blood in the platelet-rich plasma group or normal saline in the control group.
      Graft survival, cutaneous blood flow, CD31-stained vessels, and vascular
      endothelial growth factor protein levels were examined. RESULTS: Twelve days
      after surgery, graft viability in the platelet-rich plasma group was higher than
      in the control group. Blood perfusion was also higher in the platelet-rich plasma
      group. Compared with the control group, the number of CD31 blood vessels and
      vascular endothelial growth factor expression levels were significantly increased
      in the platelet-rich plasma group. CONCLUSIONS: The authors' results suggest that
      platelet-rich plasma restores the perfusion of composite grafts by enhancing
      revascularization and may exert therapeutic effects on the survival of composite
      grafts.

PMID- 24732655
TI  - Functional free muscle transfer for upper extremity reconstruction.
AB  - BACKGROUND: Functional losses in the upper extremity that cannot be restored by
      nerve or tendon transfer present a treatment dilemma to the reconstructive
      surgeon. Common indications for functional free muscle transfer include late
      reconstruction of brachial plexus injuries, traumatic muscle loss, Volkmann
      ischemic contracture, loss resulting from oncologic resection, and congenital
      absence of motor function as seen in arthrogryposis. METHODS: This article
      reviews the authors' experience in upper extremity reconstruction using
      functional free muscle transfer. The indications and technique for functional
      free muscle transfer in the upper extremity are reviewed. Surgical details for
      sites of reconstruction and the nuances of harvesting the main donor muscles are
      presented. RESULTS: Specific cases and outcome reviews for several series of
      functional free muscle transfers are presented. CONCLUSION: Functional free
      muscle transfer is the best and final option for restoring function in an
      otherwise nonreconstructible limb.

PMID- 24732654
TI  - The role of stem cells in aesthetic surgery: fact or fiction?
AB  - BACKGROUND: Stem cells are attractive candidates for the development of novel
      therapies, targeting indications that involve functional restoration of defective
      tissue. Although most stem cell therapies are new and highly experimental, there
      are clinics around the world that exploit vulnerable patients with the hope of
      offering supposed stem cell therapies, many of which operate without credible
      scientific merit, oversight, or other patient protection. METHODS: The authors
      review the potential and the drawbacks of incorporation of stem cells in cosmetic
      procedures. A review of U.S. Food and Drug Administration-approved indications
      and ongoing clinical trials with adipose stem cells is provided. Furthermore, a
      "snapshot" analysis of Web sites using the search terms "stem cell therapy" or
      "stem cell treatment" or "stem cell facelift" was performed. RESULTS: Despite the
      protective net cast by regulatory agencies such as the U.S. Food and Drug
      Administration and professional societies such as the American Society of Plastic
      Surgeons, the authors are witnessing worrying advertisements for procedures such
      as stem cell face lifts, stem cell breast augmentations, and even stem cell
      vaginal rejuvenation. The marketing and promotion of stem cell procedures in
      aesthetic surgery is not adequately supported by clinical evidence in the
      majority of cases. CONCLUSIONS: Stem cells offer tremendous potential, but the
      marketplace is saturated with unsubstantiated and sometimes fraudulent claims
      that may place patients at risk. With plastic surgeons at the forefront of stem
      cell-based regenerative medicine, it is critically important that they provide an
      example of a rigorous approach to research, data collection, and advertising of
      stem cell therapies.

PMID- 24732656
TI  - Multiple sclerosis.

PMID- 24732657
TI  - The essential role of T cells in multiple sclerosis: a reappraisal.
AB  - Multiple sclerosis is an inflammatory demyelinating disease of the central
      nervous system in which destruction of myelin and nerve axons has been shown to
      be mediated by immune mechanisms. Although the focus of research has been
      traditionally on T cells as key mediators of the immunopathology, more recent
      efforts at understanding this complex disorder have been directed increasingly at
      other cellular and humoral elements of the immune response. This review is a
      reappraisal of the crucial role of T cells, in particular the CD4+ helper T-cell
      subset, in multiple sclerosis. Recent evidence is discussed underlining the
      predominant contribution of T-cell-associated genes to the genome-wide
      association study results of multiple sclerosis susceptibility, the loss of T
      cell quiescence in the conversion from clinically isolated syndrome to clinically
      definite multiple sclerosis, and the fact that T cells represent the main target
      of effective immunomodulatory and immunosuppressive treatments in multiple
      sclerosis. 

PMID- 24732658
TI  - Advances in the treatment of relapsing-remitting multiple sclerosis.
AB  - This article reviews and discusses the approved and emerging therapies for
      multiple sclerosis (MS). MS is a chronic and disabling immune-mediated disease of
      the central nervous system (CNS) that affects mainly young adults. MS imposes a
      huge economic burden on healthcare systems and the society. Although the last 20
      years have brought a continuous expansion in therapeutic options, there are still
      unmet needs in MS management. Available MS drugs have varying degrees of efficacy
      in reducing relapse risk. The long-term term effects of these treatments are
      incompletely known. New therapies, along with variations of currently available
      treatments, may prove more effective and tolerable than the available drugs.
      Treatments for MS differ with respect to the mode of administration, tolerability
      and likelihood of treatment adherence, side effects, and risk of major toxicity.
      The armamentarium of approved disease-modifying therapies in MS and those in
      development include: (1) the first approved, moderately effective, injectable
      interferon-beta and glatiramer acetate; (2) oral drugs (fingolimod, laquinimod,
      teriflunomide, dimethyl fumarate); (3) monoclonal antibodies (rituximab,
      ocrelizumab, ofatumumab, daclizumab, alemtuzumab); and (4) immunosuppressive
      agents (e.g. mitoxantrone). The place of each drug in the therapeutic algorithm
      is dependent on its specific risk-benefit profile. Patients' clinical and
      paraclinical phenotypes and biomarker profile may help to elucidate disease
      subtypes and response to therapy in the future, thus allowing treatment
      individualization. 

PMID- 24732659
TI  - Diagnostic modalities in multiple sclerosis: perspectives in children.
AB  - Pediatric multiple sclerosis (MS) represents only 2-5% of the MS population, but
      children with MS have a higher relapse rate and reach permanent disability at a
      younger age than adult-onset MS. Early and accurate diagnosis of pediatric MS is
      vital for prompt treatment to mitigate ongoing neuroinflammation and irreversible
      neurodegeneration. However, it is difficult to differentiate MS from acute
      disseminated encephalomyelitis (ADEM) and neuromyelitis optica (NMO) in pediatric
      patients, even considering the clinical, magnetic resonance imaging (MRI), and
      paraclinical findings, because the first presentation of inflammatory
      demyelination in children is often atypical. The purpose of this review is to
      summarize the clinical, neuroimaging, and paraclinical key differences between
      pediatric patients with MS, ADEM, and NMO and to discuss novel biomarkers, such
      as antibodies to aquaporin-4 (AQP4) and myelin oligodendrocyte glycoprotein
      (MOG), which may help in making a diagnosis. 

PMID- 24732660
TI  - Gene expression profiles in peripheral blood mononuclear cells of Asian
      obstructive sleep apnea patients.
AB  - BACKGROUND: Obstructive sleep apnea (OSA) syndrome is a complicated disease
      involving several pathogenic mechanisms. Microarray technology provides a high
      throughput means of identifying differentially expressed genes in patients with
      OSA. METHODS: An Affymetrix U133A gene chip was used to globally analyze the
      transcriptome of peripheral blood mononuclear cells (PBMC) in patients with OSA
      and nonapneic control participants after overnight polysomnography. RESULTS:
      Several genes were differentially expressed in patients with OSA compared with
      control participants. These genes included disintegrin and metalloproteinase
      domain 29 (ADAM29), solute carrier family 18 (vesicular acetylcholine) member 3
      (SLC18A3), cyclin-dependent kinase inhibitor 2C (CDKN2C), and fibronectin-like
      domain-containing leucine-rich transmembrane protein 2 (FLRT2). Among these
      genes, the expression levels of ADAM29 (p = 0.00003), FLRT2 (p < 0.0001), and
      SLC18A3 (p = 0.0006) were found to be possible markers of severe OSA [respiratory
      disturbance index (RDI) > 30]. CONCLUSION: Our data suggest that PCMC expression
      of ADAM29, FLRT2, and SLC18A3 could be assessed as part of a routine screen to
      help identify individuals at risk of severe OSA in Asian populations.

PMID- 24732661
TI  - Nutritional status assessed by scored patient-generated subjective global
      assessment associated with length of hospital stay in adult patients receiving an
      appendectomy.
AB  - BACKGROUND: Malnutrition has been associated with poor health outcomes in
      hospitalized patients. This study assessed the validity of the scored patient
      generated subjective global assessment (PG-SGA) in adult patients who had
      undergone an open appendectomy, and examined the association of this assessment
      tool with length of hospital stay. METHODS: Nutritional status was determined by
      using the scored PG-SGA in adult patients (n = 86) who had undergone an open
      appendectomy within 24 hours of admission. Variables were compared between well
      nourished and malnourished participants. Regression analysis was used to identify
      potential predictors for length of hospital stay. Receiver operator
      characteristic (ROC) analysis was used to examine the validity of the PG-SGA
      score to predict the nutritional status. RESULTS: On admission, 17% of the study
      subjects were malnourished and associated with a significantly older age (53.0
      vs. 39.5), greater PG-SGA score (8 vs. 2), higher comorbidity (67% vs. 27%), and
      longer length of hospital stay (6.9 d vs. 4.1 d). The PG-SGA score and
      comorbidity were the determined risk factors for length of hospital stay after
      performing multiple regression analysis. Furthermore, the PG-SGA score had a
      significantly positive correlation with length of hospital stay (Spearman's rho =
      0.378, p < 0.001). The area under the ROC curve indicating the PG-SGA score,
      compared with nutritional status, is 0.9751. CONCLUSIONS: The scored PG-SGA in
      adults receiving an appendectomy is significantly associated with length of
      hospital stay, and is an effective tool for assessing the nutritional status of
      patients with cancer and chronic illness, as well as of patients with acute
      surgical abdomen.

PMID- 24732662
TI  - Influence of lumbar curvature and rotation on forward flexibility in idiopathic
      scoliosis.
AB  - BACKGROUND: Lumbar spine facet joints are arranged sagittally and mainly provide
      forward flexibility. Rotation of the lumbar vertebral body and coronal plane
      deformity may influence the function of lumbar forward flexibility. We
      hypothesize that the more advanced axial and coronal plane deformity could cause
      more limitation on forward flexibility in patients with idiopathic scoliosis.
      METHODS: Between January 2011 and August 2011, 85 patients with adolescent
      idiopathic scoliosis were enrolled in this study. The proximal thoracic, major
      thoracic, thoracolumbar/lumbar (TL/L), and lumbar (L1/L5) curves were measured by
      Cobb's method. Lumbar apical rotation was graded using the Nash-Moe score. Lumbar
      forward flexibility was measured using the sit and reach (S and R) test.
      Statistical analysis was performed using one-way analysis of variance (ANOVA),
      Spearman's and Pearson's correlation coefficients. RESULTS: The mean age was 16.1
      +/- 2.84 years. The mean proximal thoracic, major thoracic, TL/L, and L1/L5
      curves were 17.61 degrees  +/- 8.92, 25.56 degrees  +/- 11.61, 26.09 degrees  +/-
      8.6, and 15.10 degrees  +/- 7.85, respectively. The mean S and R measurement was
      25.56 +/- 12.33 cm. The magnitude of the TL/L and L1/L5 curves was statistically
      positively related to vertebral rotation (r(s) = 0.580 and 0.649, respectively).
      The correlation between the S and R test and both the TL/L and L1/L5 curves was
      negative (r(p) = -0.371 and -0.595, respectively). Besides, the S and R test also
      demonstrated a significant negative relationship with vertebral rotation (rs = 
      0.768). CONCLUSION: In patients with idiopathic scoliosis, spinal deformity can
      diminish lumbar forward flexibility. Higher lumbar curvature and rotation lead to
      greater restriction of lumbar flexion.

PMID- 24732663
TI  - Total knee arthroplasty in patients with dialysis: early complications and
      mortality.
AB  - BACKGROUND: Total hip arthroplasty (THA) in patients on long-term hemodialysis
      may result in a high prevalence of complications which related to nature of the
      disease, and associated cardiovascular conditions. However, the result of total
      knee artrhopalsty (TKA) in those patients is not clear. The purpose of this study
      was to retrospectively evaluate the early mortality and complications of TKA
      performed in patients with dialysis. METHODS: We retrospectively evaluated 15
      dialysis patients (18 knees) who underwent TKA using antibiotic-loaded cement
      fixation. Fourteen patients had maintained hemodialysis and one patient had
      continuous ambulatory peritoneal dialysis. The function of the knee was evaluated
      before operation and postoperatively using Knee Society evaluating system.
      Postoperative complications and mortality were recorded for all patients. The
      average follow up period was 25 months (6 to 59 months). RESULTS: There were no
      mortalities including short-term (<=90 days) or long-term (>90 days) follow up.
      The mean knee and function scores improved from preoperative 36 points (27~46)
      and 19.4 points (10~35) to 79 points (68~87) and 81 points (70~95) respectively
      at the latest follow up. One (6.7%) patient had early postoperative pneumonia
      (<=90 days). The late (>90 days) complication rate was 20% including 1 sepsis
      with toe gangrene, 1 recurrent stroke and 1 acute myocardiac infarction. There
      was no deep prosthetic joint infection or loosening of the components.
      CONCLUSION: TKA with antibiotic-loaded cement resulted in a substantial low short
      term mortality and deep infections in 15 patients with dialysis. However, a
      longer term follow up is necessary.

PMID- 24732664
TI  - Serum levels of melatonin and cytokines in multiple sclerosis.
AB  - Cytokines are important factors of the immune system in autoimmune diseases such
      as multiple sclerosis (MS) in which damage caused by oxidants plays a major role
      in the pathology. Melatonin secreted by the pineal gland has recently been
      considered as an antioxidant. The purpose of this study was to determine the
      relationship between melatonin and cytokines in patients with MS. Thirty patients
      with MS and 30 healthy controls were selected. Serum levels of melatonin and
      cytokines, including interleukin-4, interferon-gamma, and tumor necrosis factor
      alpha (TNF-alpha), were detected in all participants by the enzyme-linked
      immunosorbent assay (ELISA) method. There was a significant difference between
      patient and control groups in the levels of melatonin and TNF-alpha. Also, no
      significant correlation between the serum levels of melatonin and cytokines in
      both patient and control groups was seen. We concluded that decrease of melatonin
      and subsequent increase of pro-inflammatory cytokine, TNF-alpha, could be a
      factor in the inflammatory reactions in the pathologic process of MS. 

PMID- 24732665
TI  - Individual choices in dynamic networks: an experiment on social preferences.
AB  - Game-theoretic models of network formation typically assume that people create
      relations so as to maximize their own outcome in the network. Recent experiments
      on network formation suggest that the assumption of self-interest might be
      unwarranted and that social preferences, such as altruism and inequality
      aversion, play a role in the formation of social networks. We developed an
      experiment to systematically investigate whether people show preferences for
      outcomes of others during network formation. We find that such preferences play a
      role when network decisions degenerate to simple two-person decision tasks. In
      more complex environments, however, we find little evidence for social
      preferences as a significant decision criterion. Furthermore, we find some
      evidence for farsighted behavior in network formation. 

PMID- 24732666
TI  - Physical Biology : challenges for our second decade.
AB  - It is quite an honor to be asked to become the third editor-in-chief of Physical
      Biology . I am following in the footsteps of Tim Newman, who served with energy
      and enthusiasm. Hopefully, the entire community fully appreciates his
      contributions to moving the field forward. Thank you, Tim! With the honor,
      however, goes a clear responsibility. Our journal has survived its birth pangs
      and emerged as a serious venue for publishing quality research papers using
      physical science to address the workings of living matter. With the support of
      scientists in this field and with the ongoing commitment of the IOP, we have
      successfully reached adolescence. Yet, there is clearly much room to grow and
      there are clear challenges in defining and maintaining our special niche in the
      publishing landscape. In this still-developing state, the journal very much
      mimics the state of the field of physical biology itself. Few scientists continue
      to question the relevance of physical science for the investigation of the living
      world. But, will our new perspective and the methods that come with it really
      lead to radically new principles of how life works? Or, will breakthroughs
      continue to come from experimental biology (perhaps aided by the traditional
      physicist-as-tool-builder paradigm), leaving us to put quantitative touches on
      established fundamentals? In thinking about these questions for the field and for
      the journal, I have tried to understand what is really unique about our joint
      endeavors. I have become convinced that living matter represents a new challenge
      to our physical-science based conceptual framework. Not only is it far from
      equilibrium, as has been generally recognized, but it violates our simple notions
      of the separability of constituents, their interactions and the resulting large
      scale behavior. Unlike, say, atomic physicists who can do productive research
      while safely ignoring the latest developments in QCD (let alone particle physics
      at higher energies), we do not yet understand when the details of proteins and
      nucleic acids structure and function can be assumed constant when considering the
      cell. This problem is even more serious as we try to set higher sights and think
      of cells as constituents of tissue, organ and organism. Trying to understand
      higher-order biological systems is a bit like trying to play a board game where
      the pieces and rules are constantly changing, somehow in concert with what is
      happening at the scale of the game. Others will undoubtedly have their own view
      of what is really difficult and different about living systems. One of the roles
      of Physical Biology should therefore be to provide a needed forum to address some
      of these really difficult questions. Of course, most papers will operate with the
      safety-setting on, and will use established ideas in physics, either experimental
      or theoretical, to further our quantitative appreciation of living systems. These
      papers are without doubt an absolutely necessary part of the field, and we hope
      that our journal can serve as a home for the best of these. But, my real hope is
      that we can attract papers that really try to break new ground, that suggest ways
      in which the living world is not just an extremely messy example of the same
      phenomena that can be studied in non-biological contexts. Amazingly, this hope is
      actually shared by many leading biologists. In one of the most influential papers
      on cancer research in the past decades. Hanahan and Weinberg argue that 'one day,
      we imagine that cancer biology and treatment-at present, a patchwork quilt of
      cell biology, genetics, histopathology, biochemistry, immunology, and
      pharmacology-will become a science with a conceptual structure and logical
      coherence that rivals that of chemistry or physics.' We should take up the
      challenge, not just for cancer, and Physical Biology should help. Figuring out
      exactly how best to do this is now my responsibility, and I look forward to
      hearing from you and working with all of you, in order to make it happen. 

PMID- 24732668
TI  - The USDA barley core collection: genetic diversity, population structure, and
      potential for genome-wide association studies.
AB  - New sources of genetic diversity must be incorporated into plant breeding
      programs if they are to continue increasing grain yield and quality, and
      tolerance to abiotic and biotic stresses. Germplasm collections provide a source
      of genetic and phenotypic diversity, but characterization of these resources is
      required to increase their utility for breeding programs. We used a barley SNP
      iSelect platform with 7,842 SNPs to genotype 2,417 barley accessions sampled from
      the USDA National Small Grains Collection of 33,176 accessions. Most of the
      accessions in this core collection are categorized as landraces or
      cultivars/breeding lines and were obtained from more than 100 countries. Both
      STRUCTURE and principal component analysis identified five major subpopulations
      within the core collection, mainly differentiated by geographical origin and
      spike row number (an inflorescence architecture trait). Different patterns of
      linkage disequilibrium (LD) were found across the barley genome and many regions
      of high LD contained traits involved in domestication and breeding selection. The
      genotype data were used to define 'mini-core' sets of accessions capturing the
      majority of the allelic diversity present in the core collection. These 'mini
      core' sets can be used for evaluating traits that are difficult or expensive to
      score. Genome-wide association studies (GWAS) of 'hull cover', 'spike row
      number', and 'heading date' demonstrate the utility of the core collection for
      locating genetic factors determining important phenotypes. The GWAS results were
      referenced to a new barley consensus map containing 5,665 SNPs. Our results
      demonstrate that GWAS and high-density SNP genotyping are effective tools for
      plant breeders interested in accessing genetic diversity in large germplasm
      collections. 

PMID- 24732669
TI  - Molecular and cellular regulation of hypothalamic melanocortin neurons
      controlling food intake and energy metabolism.
AB  - The brain receives and integrates environmental and metabolic information,
      transforms these signals into adequate neuronal circuit activities, and generates
      physiological behaviors to promote energy homeostasis. The responsible neuronal
      circuitries show lifetime plasticity and guaranty metabolic health and survival.
      However, this highly evolved organization has become challenged nowadays by
      chronic overload with nutrients and reduced physical activity, which results in
      an ever-increasing number of obese individuals worldwide. Research within the
      last two decades has aimed to decipher the responsible molecular and cellular
      mechanisms for regulation of the hypothalamic melanocortin neurons, which have a
      key role in the control of food intake and energy metabolism. This review maps
      the central connections of the melanocortin system and highlights its global
      position and divergent character in physiological and pathological metabolic
      events. Moreover, recently uncovered molecular and cellular processes in
      hypothalamic neurons and glial cells that drive plastic morphological and
      physiological changes in these cells, and account for regulation of food intake
      and energy metabolism, are brought into focus. Finally, potential functional
      interactions between metabolic disorders and psychiatric diseases are discussed.

PMID- 24732667
TI  - Effects in the use of a genetically engineered strain of Lactococcus lactis
      delivering in situ IL-10 as a therapy to treat low-grade colon inflammation.
AB  - Irritable bowel syndrome (IBS) is a gastrointestinal disorder characterized by
      chronic abdominal pain, discomfort, and bloating. Interestingly, there is now
      evidence of the presence of a low-grade inflammatory status in many IBS patients,
      including histopathological and mucosal cytokine levels in the colon, as well as
      the presence of IBS-like symptoms in quiescent inflammatory bowel disease (IBD).
      The use of a genetically engineered food-grade bacterium, such as Lactococcus
      lactis, secreting the anti-inflammatory cytokine IL-10 has been proven by many
      pre-clinical studies to be a successful therapy to treat colon inflammation. In
      this study, we first reproduced the recovery-recurrence periods observed in IBS
      patients in a new chronic model characterized by 2 episodes of DiNitro
      BenzeneSulfonic-acid (DNBS)-challenge and we tested the effects of a recombinant
      strain of L. lactis secreting IL-10 under a Stress-Inducible Controlled
      Expression (SICE) system. In vivo gut permeability, colonic serotonin levels,
      cytokine profiles, and spleen cell populations were then measured as readouts of
      a low-grade inflammation. In addition, since there is increasing evidence that
      gut microbiota tightly regulates gut barrier function, tight junction proteins
      were also measured by qRT-PCR after administration of recombinant L. lactis in
      DNBS-treated mice. Strikingly, oral administration of L. lactis secreting active
      IL-10 in mice resulted in significant protective effects in terms of
      permeability, immune activation, and gut-function parameters. Although
      genetically engineered bacteria are, for now, used only as a "proof-of-concept,"
      our study validates the interest in the use of the novel SICE system in L. lactis
      to express therapeutic molecules, such as IL-10, locally at mucosal surfaces.

PMID- 24732670
TI  - Dietary triglycerides act on mesolimbic structures to regulate the rewarding and
      motivational aspects of feeding.
AB  - Circulating triglycerides (TGs) normally increase after a meal but are altered in
      pathophysiological conditions, such as obesity. Although TG metabolism in the
      brain remains poorly understood, several brain structures express enzymes that
      process TG-enriched particles, including mesolimbic structures. For this reason,
      and because consumption of high-fat diet alters dopamine signaling, we tested the
      hypothesis that TG might directly target mesolimbic reward circuits to control
      reward-seeking behaviors. We found that the delivery of small amounts of TG to
      the brain through the carotid artery rapidly reduced both spontaneous and
      amphetamine-induced locomotion, abolished preference for palatable food and
      reduced the motivation to engage in food-seeking behavior. Conversely, targeted
      disruption of the TG-hydrolyzing enzyme lipoprotein lipase specifically in the
      nucleus accumbens increased palatable food preference and food-seeking behavior.
      Finally, prolonged TG perfusion resulted in a return to normal palatable food
      preference despite continued locomotor suppression, suggesting that adaptive
      mechanisms occur. These findings reveal new mechanisms by which dietary fat may
      alter mesolimbic circuit function and reward seeking. 

PMID- 24732671
TI  - Estradiol for treatment-resistant schizophrenia: a large-scale randomized
      controlled trial in women of child-bearing age.
AB  - Many women with schizophrenia remain symptomatic despite optimal use of current
      therapies. While previous studies suggest that adjunctive oestrogen therapy might
      be effective, large-scale clinical trials are required before clinical
      applications are possible. This study is the first large-scale randomized
      controlled trial in women with treatment-resistant schizophrenia. This Definitive
      Oestrogen Patch Trial was an 8-week, three-arm, double-blind, randomized
      controlled trial conducted between 2006 and 2011. The 183 female participants
      were aged between 18 and 45 (mean = 35 years), with schizophrenia or
      schizoaffective disorder and ongoing symptoms of psychosis (Positive and Negative
      Syndrome Scale, PANSS score>60) despite a stable dose of antipsychotic medication
      for at least 4 weeks. Mean duration of illness was more than 10 years.
      Participants received transdermal estradiol 200 MUg, transdermal estradiol 100
      MUg or an identical placebo patch. For the 180 women who completed the study, the
      a priori outcome measure was the change in PANSS score measured at baseline and
      days 7, 14, 28 and 56. Cognition was assessed at baseline and day 56 using the
      Repeatable Battery of Neuropsychological Status. Data were analysed using latent
      growth curve modelling. Both estradiol groups had greater decreases in PANSS
      positive, general and total symptoms compared with the placebo group (P<0.01),
      with a greater effect seen for 200 MUg than 100 MUg estradiol. The largest effect
      size was for the positive subscale of PANSS in the estradiol 200 MUg treatment
      group (effect size 0.44, P<0.01). This study shows estradiol is an effective and
      clinically significant adjunctive therapy for women with treatment-resistant
      schizophrenia, particularly for positive symptoms.

PMID- 24732672
TI  - Analysis of prostate-specific antigen transcripts in chimpanzees, cynomolgus
      monkeys, baboons, and African green monkeys.
AB  - The function of prostate-specific antigen (PSA) is to liquefy the semen coagulum
      so that the released sperm can fuse with the ovum. Fifteen spliced variants of
      the PSA gene have been reported in humans, but little is known about alternative
      splicing in nonhuman primates. Positive selection has been reported in sex- and
      reproductive-related genes from sea urchins to Drosophila to humans; however,
      there are few studies of adaptive evolution of the PSA gene. Here, using
      polymerase chain reaction (PCR) product cloning and sequencing, we study PSA
      transcript variant heterogeneity in the prostates of chimpanzees (Pan
      troglodytes), cynomolgus monkeys (Macaca fascicularis), baboons (Papio hamadryas
      anubis), and African green monkeys (Chlorocebus aethiops). Six PSA variants were
      identified in the chimpanzee prostate, but only two variants were found in
      cynomolgus monkeys, baboons, and African green monkeys. In the chimpanzee the
      full-length transcript is expressed at the same magnitude as the transcripts that
      retain intron 3. We have found previously unidentified splice variants of the PSA
      gene, some of which might be linked to disease conditions. Selection on the PSA
      gene was studied in 11 primate species by computational methods using the
      sequences reported here for African green monkey, cynomolgus monkey, baboon, and
      chimpanzee and other sequences available in public databases. A codon-based
      analysis (dN/dS) of the PSA gene identified potential adaptive evolution at five
      residue sites (Arg45, Lys70, Gln144, Pro189, and Thr203). 

PMID- 24732673
TI  - Insulin-sensitizing effect of LXR agonist T0901317 in high-fat fed rats is
      associated with restored muscle GLUT4 expression and insulin-stimulated AS160
      phosphorylation.
AB  - BACKGROUND/AIM: Liver X receptors (LXRs) are ligand-activated transcription
      factors that were shown to stimulate hepatic lipogenesis leading to liver
      steatosis and hypertriglyceridemia. Despite their pro-lipogenic action, LXR
      activators normalize glycemia and improve insulin sensitivity in rodent models of
      type 2 diabetes. Antidiabetic action of LXR agonists is thought to result from
      suppression of hepatic gluconeogenesis. However, it remains unclear whether LXR
      activation affects muscle insulin sensitivity. In the present study we attempted
      to answer this question. METHODS: The experiments were performed on male Wistar
      rats fed for 5 weeks on either standard chow or high fat diet. The latter group
      was further divided into two subgroups receiving either selective LXR agonist -
      T0901317 (10mg/kg/d) or vehicle during the last week of the experiment. All
      animals were then anaesthetized and samples of the soleus as well as red and
      white sections of the gastrocnemius muscle were excised. RESULTS: As expected,
      administration of T0901317 to high-fat fed rats augmented diet-induced
      hyperlipidemia. Nevertheless, it also normalized glucose tolerance and improved
      insulin-stimulated glucose uptake in isolated soleus muscle. In addition, LXR
      agonist completely restored glucose transporter 4 expression and insulin
      stimulated Akt substrate of 160 kDa phosphorylation in all investigated muscles.
      Insulin-sensitizing effect of T0901317 was not related to changes in
      intramuscular level of lipid mediators of insulin resistance, since neither
      diacylglycerols nor ceramide content was affected by the treatment. CONCLUSION:
      We conclude that improvement in muscle insulin sensitivity is one of the
      mechanisms underlying the antidiabetic action of LXR activators.

PMID- 24732674
TI  - Genetics of congenital hypogonadotropic hypogonadism in Denmark.
AB  - Congenital hypogonadotropic hypogonadism (CHH) is a rare disorder characterized
      by incomplete/absent puberty caused by deficiency or defective action of
      gonadotropin-releasing hormone (GnRH). The phenotypic features of patients with
      CHH vary from genital hypoplasia and absent puberty to reversal of HH later in
      life. We examined the genetics and clinical features of CHH in Denmark. Forty-one
      male patients were screened for mutations in KAL1, FGFR1, FGF8, PROK2, PROKR2,
      GNRHR, TAC3, TACR3, and KISS1R. CHD7 was screened in two patients with hearing
      loss. In 12 patients, a molecular genetic cause for CHH was found. Four patients
      had mutations in KAL1 (C105VfsX13, C53X, ex5-8del, R257X), and five in FGFR1
      (G97S, R209C, A512V, R646W, and c.1614C>T, (p.I538I), predicted to affect
      splicing). All 9 had severe HH (cryptorchidism and/or micropenis), and 2 had
      cleft lip/palate. One patient with a previously reported homozygous R262Q
      mutation in GNRHR displayed fascinating temporal variation in his phenotype. Two
      patients with hearing loss had CHD7 mutations (c.7832_7841del (p.K2611MfsX25) and
      c.2443-2A>C), confirming that CHH patients with CHARGE syndrome-associated
      features should be screened for mutations in CHD7.

PMID- 24732675
TI  - Brain tumors in Turner syndrome.

PMID- 24732677
TI  - Karl Rickels: a tribute on his 90th birthday.

PMID- 24732676
TI  - Effects of prehospital 12-lead ECG on processes of care and mortality in acute
      coronary syndrome: a linked cohort study from the Myocardial Ischaemia National
      Audit Project.
AB  - OBJECTIVE: To describe patterns of prehospital ECG (PHECG) use and determine its
      association with processes and outcomes of care in patients with ST-elevation
      myocardial infarction (STEMI) and non-STEMI. METHODS: Population-based linked
      cohort study of a national myocardial infarction registry. RESULTS: 288 990
      patients were admitted to hospitals via emergency medical services (EMS) between
      1 January 2005 and 31 December 2009. PHECG use increased overall (51% vs 64%,
      adjusted OR (aOR) 2.17, 95% CI 2.12 to 2.22), and in STEMI (64% vs 79%, aOR 2.34,
      95% CI 2.25 to 2.44). Patients who received PHECG were younger (71 years vs 74
      years, P<0.0001); and less likely to be female (33.1% vs 40.3%, OR 0.87, 95% CI
      0.86 to 0.89), or to have comorbidities than those who did not. For STEMI,
      reperfusion was more frequent in those having PHECG (83.5% vs 74.4%, p<0.0001).
      PHECG was associated with more primary percutaneous coronary intervention
      patients achieving call-to-balloon time <90 min (27.9% vs 21.4%, aOR 1.38, 95% CI
      1.24 to 1.54) and more patients who received fibrinolytic therapy achieving door
      to-needle time <30 min (90.6% vs 83.7%, aOR 2.13, 95% CI 1.91 to 2.38). Patients
      with PHECG exhibited significantly lower 30-day mortality rates than those who
      did not (7.4% vs 8.2%, aOR 0.94, 95% CI 0.91 to 0.96). CONCLUSIONS: Findings from
      this national MI registry demonstrate a survival advantage in STEMI and non-STEMI
      patients when PHECG was used.

PMID- 24732678
TI  - Distinct strategies in the treatment of epidural hematoma in children: clinical
      considerations.
AB  - BACKGROUND: Epidural hematoma (EDH) is the most common form of intracranial
      bleeding following head trauma in pediatric patients. It may develop into a life
      threatening pathology, requiring an immediate neurosurgical intervention.
      However, due to an increasing number of posttrauma CT scans most pediatric EDH
      patients can be treated conservatively, because of minor dimensions of the clot
      and the possibility of quick control scanning. AIM: Evaluation of distinct
      strategies in the treatment of EDH patients in our department between January
      2007 and December 2012. RESULTS: During this period a total number of 221
      patients with EDH were enrolled in the study. Seventy-seven of them (35%)
      underwent surgical procedures. One hundred and forty-four patients (65%) were
      treated conservatively. The dominating age group among nonsurgical patients was 0
      4 years (85 cases, 61% of the nonsurgical group). In most of these cases a small
      epidural blood collection with inconsiderable dynamics was observed. Twenty-one
      patients from this age group (20%) were treated operatively. Among older children
      (5-18 years) surgical treatment was implemented in 56 (49%) cases. CONCLUSIONS:
      (1) EDH may be successfully treated conservatively with the use of control CT
      scans. (2) Smaller blood clots dominate in younger patients. (3) Surgical
      intervention is required more commonly in older patients.

PMID- 24732679
TI  - Partial volume corrected 18F-FDG PET mean standardized uptake value correlates
      with prognostic factors in breast cancer.
AB  - AIM: The aim of this paper was to assess the prognostic role of pretherapy
      partial volume corrected (PVC) 18F-fluorodeoxyglucose mean standardized uptake
      value (SUV) in breast cancer (BC). METHODS: Forty oncological patients, BC
      diagnosed by biopsy, with breast tumor mass diameter >1 cm measured to the
      mammography, designed for surgical intervention, underwent a pretherapy semi
      quantitative 18F-FDG positron emission tomography/computed tomography (18F-FDG
      PET/CT) whole-body study for tumor staging. Mean Body-Weight Standardized Uptake
      Value with Correction for Partial Volume effect (PVC- SUVBW-mean) was calculated
      in all mammary detected lesions. Excised tissues from primitive BC were sectioned
      and classified according to the WHO guidelines, evaluating biological features.
      Univariate (Mann-Withney/Kruskal-Wallis) and multivariate (linear regression,
      hierarchical clustering) statistical tests were performed between PVC-SUVBW-mean
      and biological indexes. ROC analysis was performed. PVC-SUVBW-mean thresholds
      were derived allowing to distinguish groups of BC patients with different
      biological characteristics. Specificity and Sensitivity were also calculated.
      RESULTS: Statistical and multiple correlations between pretherapy 18F-FDG PET PVC
      SUVBW-mean and histological type, grade, ER/PgR hormone receptors and Mib-1
      cellular proliferation index were found. In our samples, PVC-SUVBW-mean <~4 g/cc
      was found correlated to BC patients with Invasive Lobular Carcinoma (ILC) or well
      differentiated Invasive Ductal Carcinoma (IDC), a positive expression of ER and
      PgR and a negative expression of MiB-1, while PVC-SUVBW-mean >~7.00 is associated
      to BC patients with moderately and poorly differentiated IDC, negative expression
      of ER and PgR and a positive expression of MiB-1. CONCLUSION: Pretherapy PVC 18F
      FDG PET PVC-SUVBW-mean measurement correlates with prognostic factors in BC and
      could be used to stratify patients before intervention.

PMID- 24732680
TI  - Metabolic impact of partial volume correction of [18F]FDG PET-CT oncological
      studies on the assessment of tumor response to treatment.
AB  - AIM: The aim of this work is to evaluate the metabolic impact of Partial Volume
      Correction (PVC) on the measurement of the Standard Uptake Value (SUV) from
      [18F]FDG PET-CT oncological studies for treatment monitoring purpose. METHODS:
      Twenty-nine breast cancer patients with bone lesions (42 lesions in total)
      underwent [18F]FDG PET-CT studies after surgical resection of breast cancer
      primitives, and before (PET-II) chemotherapy and hormone treatment. PVC of bone
      lesion uptake was performed on the two [18F]FDG PET-CT studies, using a method
      based on Recovery Coefficients (RC) and on an automatic measurement of lesion
      metabolic volume. Body-weight average SUV was calculated for each lesion, with
      and without PVC. The accuracy, reproducibility, clinical feasibility and the
      metabolic impact on treatment response of the considered PVC method was
      evaluated. RESULTS: The PVC method was found clinically feasible in bone lesions,
      with an accuracy of 93% for lesion sphere-equivalent diameter >1 cm. Applying
      PVC, average SUV values increased, from 7% up to 154% considering both PET-I and
      PET-II studies, proving the need of the correction. As main finding, PVC modified
      the therapy response classification in 6 cases according to EORTC 1999
      classification and in 5 cases according to PERCIST 1.0 classification.
      CONCLUSION: PVC has an important metabolic impact on the assessment of tumor
      response to treatment by [18F]FDG PET-CT oncological studies.

PMID- 24732681
TI  - Phylogenetic position of Myriapoda revealed by 454 transcriptome sequencing.
AB  - Myriapods had been considered closely allied to hexapods (insects and relatives).
      However, analyses of molecular sequence data have consistently placed Myriapoda
      either as a sister group of Pancrustacea, comprising crustaceans and hexapods,
      and thereby supporting the monophyly of Mandibulata, or retrieved Myriapoda as a
      sister group of Chelicerata (spiders, ticks, mites and allies). In addition, the
      relationships among the four myriapod groups (Pauropoda, Symphyla, Diplopoda,
      Chilopoda) are unclear. To resolve the phylogeny of myriapods and their
      relationship to other main arthropod groups, we collected transcriptome data from
      the symphylan Symphylella vulgaris, the centipedes Lithobius forficatus and
      Scolopendra dehaani, and the millipedes Polyxenus lagurus, Glomeris pustulata and
      Polydesmus angustus by 454 sequencing. We concatenated a multiple sequence
      alignment that contained 1550 orthologous single copy genes (1,109,847 amino acid
      positions) from 55 euarthropod and 14 outgroup taxa. The final selected alignment
      included 181 genes and 37,425 amino acid positions from 55 taxa, with eight
      myriapods and 33 other euarthropods. Bayesian analyses robustly recovered
      monophyletic Mandibulata, Pancrustacea and Myriapoda. Most analyses support a
      sister group relationship of Symphyla in respect to a clade comprising Chilopoda
      and Diplopoda. Inclusion of additional sequence data from nine myriapod species
      resulted in an alignment with poor data density, but broader taxon average. With
      this dataset we inferred Diplopoda+Pauropoda as closest relatives (i.e.,
      Dignatha) and recovered monophyletic Helminthomorpha. Molecular clock
      calculations suggest an early Cambrian emergence of Myriapoda ~513 million years
      ago and a late Cambrian divergence of myriapod classes. This implies a marine
      origin of the myriapods and independent terrestrialization events during myriapod
      evolution.

PMID- 24732682
TI  - Phylogenetic disassembly of species boundaries in a widespread group of
      Australian skinks (Scincidae: Ctenotus).
AB  - Scincid lizards in the genus Ctenotus represent one of Australia's most species
      rich vertebrate clades, with more than 100 recognized species. Formal diagnoses
      of many species have relied on qualitative assessments of adult color pattern,
      but the validity of many such species has not been tested in a phylogenetic
      framework. We used mitochondrial and nuclear DNA to perform the first
      phylogenetic analysis of species in the Ctenotus inornatus group, a complex of at
      least 11 nominal forms that are distributed widely across the Australian
      continent. Mitochondrial and nuclear gene phylogenies support the presence of
      multiple species in the group, but these clades largely fail to match species
      boundaries as currently defined. Multivariate analyses of color pattern indicate
      that extreme intraspecific morphological variation in this character has created
      a significant impediment to understanding taxonomic diversity in the group. Our
      results suggest that nearly all species in the C. inornatus group require
      substantial taxonomic revision, and several geographically widespread forms ("C.
      saxatilis" and "C. robustus") appear to be polyphyletic taxa drawn from
      phenotypically similar but genetically distinct lineages. We describe one new
      species and provide redescriptions for three additional species. We synonymize
      names applied to a number of genetically incoherent or otherwise poorly-defined
      forms. The results of our study highlight an acute need for population genetic
      studies of species boundaries in Australian skinks, many of which are recognized
      by morphological traits that vary greatly within and between populations. 

PMID- 24732683
TI  - Nurse practitioners and the growth of palliative medicine.
AB  - As Americans live longer they are likely to suffer from chronic, life-limiting
      illness. Because there are not enough hospice and palliative medicine (HPM)
      trained physicians to care for these people, there have been recent calls to
      increase the number of HPM trained physicians. We, however, believe that greater
      involvement of nurse practitioners (NPs) is a step in remedying this deficit. The
      philosophy and culture in which nurse practitioners are trained make them ideal
      clinicians to provide excellent palliative care. In addition, NPs are not only
      numerous, they can provide care that is on par with that provided by physicians.
      Removal of barriers to NP practice and increasing the quality of their palliative
      care education/training needs to occur in order to make this suggestion a
      reality. 

PMID- 24732684
TI  - A difficult patient.

PMID- 24732685
TI  - Disorder-induced room temperature ferromagnetism in glassy chromites.
AB  - We report an unusual robust ferromagnetic order above room temperature upon
      amorphization of perovskite [YCrO3] in pulsed laser deposited thin films. This is
      contrary to the usual expected formation of a spin glass magnetic state in the
      resulting disordered structure. To understand the underlying physics of this
      phenomenon, we combine advanced spectroscopic techniques and first-principles
      calculations. We find that the observed order-disorder transformation is
      accompanied by an insulator-metal transition arising from a wide distribution of
      Cr-O-Cr bond angles and the consequent metallization through free carriers.
      Similar results also found in YbCrO3-films suggest that the observed phenomenon
      is more general and should, in principle, apply to a wider range of oxide
      systems. The ability to tailor ferromagnetic order above room temperature in
      oxide materials opens up many possibilities for novel technological applications
      of this counter intuitive effect. 

PMID- 24732686
TI  - Caregiver Quality of Life and Daily Functioning in Relation to Ventilating Tube
      Treatment.
AB  - OBJECTIVE: Caregiver quality of life and daily functioning may improve after
      ventilating tube treatment in children with otitis media. The aims of this study
      are to assess possible changes in caregiver quality of life and daily functioning
      in relation to ventilating tube treatment and to investigate possible predictors
      for clinical success. STUDY DESIGN: Longitudinal observational study. SETTING:
      Secondary care units. METHODS: Four hundred ninety-one families were enrolled in
      the study. The Caregiver Impact Questionnaire was applied in the assessment of
      caregiver quality of life. Caregivers completed questionnaires at baseline and at
      1, 3, 6, 12, and 18 months' follow-up. Variables on caregiver daily functioning
      comprised 4 weeks' history of number of interrupted nights, absenteeism,
      cancelled social activities, and doctor visits as a result of otitis media in the
      child. RESULTS: Response rates ranged from 96% to 79%. Significant improvements
      in disease-specific quality of life were seen after treatment. The poorest
      baseline quality of life was found in caregivers of children with recurrent acute
      otitis media. Significant improvements were found on all variables on daily
      functioning. Predictors for caregiver-perceived clinical success included child
      sex, number of interrupted nights, doctor visits, absenteeism, and cancelled
      social activities. CONCLUSION: Results of this study support the notion that
      caregivers of children with otitis media with defined surgical indications
      improve their quality of life and daily functioning after ventilating tube
      treatment. Factors related to caregiver functioning and disease severity were
      found to be associated with caregivers experiencing important improvements after
      treatment.

PMID- 24732687
TI  - Novel Indocyanine Green-Phytate Colloid Technique for Sentinel Node Detection in
      Head and Neck: Mouse Study.
AB  - OBJECTIVE: Sentinel node navigation surgery using real-time, near-infrared
      imaging with indocyanine green is becoming popular by allowing head and neck
      surgeons to avoid unnecessary neck dissection. The major drawback of this method
      is its quick migration through the lymphatics, limiting the diagnostic time
      window and undesirable detection of downstream nodes. We resolved this problem by
      mixing indocyanine green (ICG) with phytate colloid to retard its migration and
      demonstrated its feasibility in a nude mouse study. STUDY DESIGN: Experimental
      prospective animal study. SETTINGS: Animal laboratory. SUBJECTS AND METHODS:
      Indocyanine green at 3 concentrations was tested to determine the optimal
      concentration for sentinel lymph node detection in a mouse model. Effect of
      indocyanine green with phytate colloid mixture solutions was also analyzed.
      Indocyanine green or mixture solution at different mixing ratios were injected
      into the tongue of nude mice and near-infrared fluorescence images were captured
      sequentially for up to 48 hours. The brightness of fluorescence in the sentinel
      lymph node and lymph nodes further downstream were assessed. RESULTS: Indocyanine
      green concentration >50 MUg/mL did not improve sentinel lymph node detection. The
      addition of phytate colloid to indocyanine green extended the period when
      sentinel lymph node was detectable. Second echelon lymph nodes were not imaged in
      mice injected with the mixture, while these were visualized in mice injected with
      indocyanine green alone. CONCLUSION: This novel technique of ICG-phytate colloid
      mixture allows prolonged diagnostic time window, prevention of downstream
      subsequent nodes detection, and improved accuracy for the detection of true
      sentinel lymph nodes.

PMID- 24732688
TI  - Ultrasound-Guided Needle Localization during Open Parotid Sialolithotomy.
AB  - OBJECTIVES: Our objective is to describe a novel operative technique for
      localization of parotid sialolithiasis, demonstrate the feasibility of the
      technique, and discuss its indications. STUDY DESIGN: Prospective study. SETTING:
      Tertiary-level academic center. SUBJECTS AND METHODS: Patients with symptomatic
      parotid sialolithiasis who had failed prior sialendoscopic extraction underwent
      ultrasound needle localization and open sialolithotomy. Data were prospectively
      collected. Independent variables included size of and location of sialoliths.
      RESULTS: Eleven patients were treated using transcutaneous ultrasound-guided
      needle placement and injection of methylene blue prior to external
      sialolithotomy. Follow-up ranged from 6 to 12 months. Ten (91.9%) patients had
      stones within the proximal one-third of the ductal lumen, and 1 (9.1%) had stones
      present within both the proximal one-third and middle one-third of the ductal
      lumen. The average surgical time was 53 +/- 10.8 minutes. The average sialolith
      length was 7.6 +/- 2 mm. The average sialolith width was 6 +/- 1.9 mm. All 11
      (100%) cases were successful for stone retrieval. Ten (91%) patients had complete
      symptom resolution, and 1 (9.1%) patient had partial resolution of symptoms. No
      patients had major complications. Three (27.3%) patients had minor complications.
      CONCLUSION: After failing a purely endoscopic approach, sialoliths of the parotid
      gland pose a problem for precise localization and treatment. Ultrasound has been
      demonstrated to be reliable for identifying sialoliths. We propose a novel
      technique and assert that ultrasound-guided needle localization is a reliable aid
      to effective external parotid sialolithotomy, especially for larger stones >4 mm
      that are not amenable to sialendoscopic retrieval.

PMID- 24732689
TI  - Delayed Sino-nasal Complications of Radiotherapy for Nasopharyngeal Carcinoma.
AB  - OBJECTIVE: There are only sporadic reports of delayed sino-nasal complications
      associated with nasopharyngeal carcinoma (NPC) treated with radiotherapy. These
      include choanal stenosis, osteoradionecrosis, chronic sinusitis, and intranasal
      synechiae. Most likely, these complications are underestimated as in many
      institutions nasal endoscopies in NPC patients are not performed routinely. The
      aim of this study was to identify the onset and incidence of delayed sino-nasal
      complications in NPC patients and their effect on quality of life (QOL). STUDY
      DESIGN: Case series with chart review. SETTING: Tertiary medical center. SUBJECTS
      AND METHODS: A retrospective chart review was performed on all patients treated
      for NPC in our institution between 1988 through 2009. The inclusion criteria
      required at least a 3-year follow-up without recurrence. Included patients were
      contacted prospectively and asked to fill a SNOT-16 questionnaire. RESULTS: Sixty
      two patients were included in our review. There were 42 males and 20 females. The
      average age at onset was 42 years. The AJCC staging for T1, T2, T3, and T4 tumors
      was 22 (35%), 11 (18%), 18 (29%), and 11 (18%), respectively. Eleven patients
      (18%) suffered from chronic sinusitis. Nine patients (15%) developed choanal
      stenosis. Five patients (8%) developed osteoradionecrosis. Two patients suffered
      from nasal synechiae. Forty-eight patients completed the SNOT-16 questionnaire.
      Patients with choanal stenosis had the lowest QOL scores out of the cohort.
      CONCLUSION: The incidence of delayed sino-nasal complications after radiation
      treatment for NPC is not negligible and should be kept in mind when addressing
      the quality of life of NPC survivors.

PMID- 24732690
TI  - Scheduled physical activity is associated with better academic performance in
      Chilean school-age children.
AB  - BACKGROUND: This study was carried out to examine the association between
      systematic physical activity and academic performance in school kids after
      controlling for potential sociodemographic and educational confounders. METHODS:
      In a random sample of 1271 students from urban Santiago, attending 5th and 9th
      grade, who took the 2009 System for the Assessment of Educational Quality (SIMCE)
      tests, we measured physical activity habits, anthropometric characteristics, and
      socioeconomic status. Academic performance was measured by the standardized SIMCE
      tests. Logistic regressions assessed the relationship between the allocation of
      time to weekly scheduled exercise, potential confounding factors, and individual
      academic performance. RESULTS: About 80% of students reported less than 2 hours
      of weekly scheduled exercise, while 10.6% and 10.2% reported 2 to 4 hours/week
      and more than 4 hours/week, respectively. Devoting more than 4 hours/week to
      scheduled exercise significantly increased (P < .01) the odds of having SIMCE
      composite z-scores >= 50th percentile (OR: 2.3, 95% CI: 1.4 to 3.6) and >= 75th
      percentile (OR: 2.1, 95% CI: 1.3-3.3). CONCLUSIONS: Better academic performance
      was associated with a higher allocation of time to scheduled exercise in school
      age children.

PMID- 24732691
TI  - Can insomnia in pregnancy predict postpartum depression? A longitudinal,
      population-based study.
AB  - BACKGROUND: Insomnia and depression are strongly interrelated. This study aimed
      to describe changes in sleep across childbirth, and to evaluate whether insomnia
      in pregnancy is a predictor of postpartum depression. METHODS: A longitudinal,
      population-based study was conducted among perinatal women giving birth at
      Akershus University Hospital, Norway. Women received questionnaires in weeks 17
      and 32 of pregnancy and eight weeks postpartum. This paper presents data from
      2,088 of 4,662 women with complete data for insomnia and depression in week 32 of
      pregnancy and eight weeks postpartum. Sleep times, wake-up times and average
      sleep durations were self-reported. The Bergen Insomnia Scale (BIS) was used to
      measure insomnia. The Edinburgh Postnatal Depression Scale (EPDS) was used to
      measure depressive symptoms. RESULTS: After delivery, sleep duration was reduced
      by 49 minutes (to 6.5 hours), and mean sleep efficiency was reduced from 84% to
      75%. However, self-reported insomnia scores (BIS) improved from 17.2 to 15.4, and
      the reported prevalence of insomnia decreased from 61.6% to 53.8%. High EPDS
      scores and anxiety in pregnancy, fear of delivery, previous depression,
      primiparity, and higher educational level were risk factors for both postpartum
      insomnia and depression. Insomnia did not predict postpartum depression in women
      with no prior history of depression, whereas women who recovered from depression
      had residual insomnia. LIMITATIONS: Depression and insomnia were not verified by
      clinical interviews. Women with depressive symptoms were less likely to remain in
      the study. CONCLUSIONS: Although women slept fewer hours at night after delivery
      compared to during late pregnancy, and reported more nights with nighttime
      awakenings, their self-reported insomnia scores improved, and the prevalence of
      insomnia according to the DSM-IV criteria decreased. Insomnia in pregnancy may be
      a marker for postpartum recurrence of depression among women with previous
      depression.

PMID- 24732692
TI  - Cost-effectiveness analysis of HLA-B*5801 testing in preventing allopurinol
      induced SJS/TEN in Thai population.
AB  - BACKGROUND: Stevens-Johnson syndrome (SJS) and Toxic Epidermal Necrolysis (TEN),
      caused by allopurinol therapy, are strongly associated with the human leukocyte
      antigen (HLA), HLA-B*5801. Identification of HLA-B*5801 genotype before
      prescribing allopurinol offers the possibility of avoiding allopurinol-induced
      SJS/TEN. As there is a paucity of evidence about economic value of such testing,
      this study aims to determine the cost-effectiveness of HLA-B*5801 testing
      compared with usual care (no genetic testing) before allopurinol administration
      in Thailand. METHODS AND FINDING: A decision analytical and Markov model was used
      to estimate life time costs and outcomes represented as quality adjusted life
      years (QALYs) gained. The model was populated with relevant information of the
      association between gene and allopurinol-induced SJS/TEN, test characteristics,
      costs, and epidemiologic data for Thailand from a societal perspective. Input
      data were obtained from the literature and a retrospective database analysis. The
      results were expressed as incremental cost per QALY gained. A base-case analysis
      was performed for patients at age 30. A series of sensitivity analyses including
      scenario, one-way, and probabilistic sensitivity analyses were constructed to
      explore the robustness of the findings. Based on a hypothetical cohort of 1,000
      patients, the incremental total cost was 923,919 THB (USD 29,804) and incremental
      QALY was 5.89 with an ICER of 156,937.04 THB (USD 5,062) per QALY gained. The
      cost of gout management, incidence of SJS/TEN, case fatality rate of SJS/TEN, and
      cost of genetic testing are considered very influential parameters on the cost
      effectiveness value of HLA-B*5801 testing. CONCLUSIONS: The genetic testing for
      HLA-B*5801 before allopurinol administration is considered a highly potential
      cost-effective intervention in Thailand. The findings are sensitive to a number
      of factors. In addition to cost-effectiveness findings, consideration of other
      factors including ethical, legal, and social implications is needed for an
      informed policy decision making.

PMID- 24732693
TI  - Prevalence, associated factors, and comorbid conditions for Meniere's disease.
AB  - OBJECTIVES: The aims of this study were to estimate the prevalence of Meniere's
      disease and investigate its relationship with: demographic factors; symptoms and
      conditions that are known or hypothesized to be associated with Meniere's
      disease; other physical diseases; mental health. DESIGN: The authors used cross
      sectional data from the UK Biobank to compare 1376 self-reported Meniere's
      participants with over 500,000 without Meniere's. The data set has comprehensive
      anthropometric measures, questionnaire data investigating health, well-being,
      diet, and medical and drug-prescribing history for each participant. The authors
      used logistic regression models to investigate the relationship of Meniere's
      disease with: demographic factors; symptoms and conditions that are known or
      hypothesized to be associated with Meniere's disease; other physical diseases;
      and mental health. RESULTS: Meniere's disease was more common in participants who
      were older (adjusted odds ratio per 10-year increase: 1.5 [95% confidence
      interval:1.4-1.6]), white (odds ratio: 1.7;1.2-2.3), female (1.4;1.3-1.6), and
      having higher body mass index categories (p < 0.001). The Meniere's group had
      greater odds of hearing difficulty (10.9;9.6-12.5), current tinnitus (68.3;47.8
      97.5), and had fallen more than once in the last year (2.1;1.8-2.5). Meniere's
      participants had greater odds of reporting at least one disease from each
      grouping of allergic, immune dysfunction, or autonomic dysfunction (2.2;1.8-2.6),
      and poor mental health (2.1;1.8-2.5). CONCLUSIONS: This study provides an
      evidence base that improves understanding of Meniere's disease. Associations were
      noted with a number of diseases, and the authors hypothesize a role for the
      autonomic nervous system and immune system dysfunction in Meniere's etiology. The
      study also highlights the physical and mental health correlates of the condition.

PMID- 24732694
TI  - Noninvasive assessment of retinal vascular oxygen content among normal and
      diabetic human subjects: a study using hyperspectral computed tomographic imaging
      spectroscopy.
AB  - PURPOSE: This pilot study was aimed to demonstrate the clinical feasibility of
      using hyperspectral computed tomographic spectroscopy to measure blood oxygen
      content in human retinal vessels. METHODS: All procedures were performed under a
      University of Southern California Institutional Review Board-approved protocol
      and after obtaining informed consent. Fifty-seven subjects with and without
      diabetic retinopathy were dilated for standard fundus photography. Fundus
      photographs and retinal vascular oxygen measurements (oximetry) were made using a
      custom-made hyperspectral computed tomographic imaging spectrometer coupled to a
      standard fundus camera. Oximetry measurements were made along arteries (Aox) and
      veins (Vox) within vessel segments that were 1 to 2 disk diameters from the optic
      disk. RESULTS: For all control subjects (n = 45), mean Aox and Vox were 93 +/- 7%
      and 65 +/- 5% (P = 0.001), respectively. For all diabetic subjects (n = 12), mean
      Aox and Vox were 90 +/- 7% and 68 +/- 5% (P = 0.001), respectively. In subjects
      with proliferative diabetic retinopathy, Aox was significantly lower, and Vox was
      significantly higher than other groups (85 +/- 4% and 71 +/- 4%, respectively; P
      = 0.04, analysis of variance). There was a highly significant difference in the
      arteriovenous difference between subjects with proliferative diabetic retinopathy
      and those in the control group (14 vs. 26%, P = 0.003). CONCLUSION: Hyperspectral
      computed tomographic spectroscopy is a clinically feasible method for measurement
      and analysis of vascular oxygen content in retinal health and disease. This study
      uses the techniques relevant to oximetry; however, the breadth of spectral data
      available through this method may be applicable to study other anatomical and
      functional features of the retina in health and disease.

PMID- 24732695
TI  - Area of peripheral retinal nonperfusion and treatment response in branch and
      central retinal vein occlusion.
AB  - PURPOSE: To evaluate the extent of peripheral retinal nonperfusion in retinal
      vein occlusion and to determine its effect on the severity of macular edema and
      response to treatment. METHODS: This prospective clinic-based cohort study
      included 32 consecutive patients with retinal vein occlusion and refractory
      macular edema evaluated using spectral domain optical coherence tomography and
      wide-field fluorescein angiography. Areas of ischemia were calculated as a
      percentage of the total visible retina (ischemic index), which was evaluated when
      macular edema was present (foveal central subfield >300 MUm) and when edema had
      resolved (foveal central subfield <= 300 MUm). Ischemic index was the main
      outcome measure. RESULTS: The mean ischemic index at study enrollment was 14.8%
      and was larger when macular edema was present compared with when edema had
      resolved (14.8 vs. 10.3%, P < 0.001). Compared with those with less nonperfusion,
      patients with ischemic index >10% had thicker mean foveal central subfield on
      optical coherence tomography (520.8 vs. 424.5 MUm, P = 0.029) and worse visual
      acuity (56.3 vs. 59 letters) with the presence of macular edema and experienced
      greater decrease in optical coherence tomography (296.1 vs. 165.3 MUm, P = 0.019)
      and gain in visual acuity (12.4 vs. 0.9 letters, P = 0.036) in response to
      treatment. CONCLUSION: The area of peripheral retinal nonperfusion is variable in
      patients with retinal vein occlusion and affects its clinical course and response
      to treatment.

PMID- 24732696
TI  - Diagnostic and therapeutic challenges.

PMID- 24732697
TI  - The relationship between pseudodrusen and choroidal thickness.
AB  - PURPOSE: To determine the relationship between pseudodrusen as evidenced by the
      presence of subretinal drusenoid deposits and choroidal thickness using a
      multimodal imaging approach. METHODS: Two sets of data were analyzed. The first
      set was composed of consecutive patients older than 60 years with either high
      myopia or pseudodrusen. Correlations were calculated between the subfoveal
      choroidal thickness and the presence of pseudodrusen. The second set of data was
      obtained from a previously published data examining 90 consecutive eyes with
      nonexudative age-related macular degeneration so that the relationship between
      pseudodrusen and subfoveal choroidal thickness could be analyzed. RESULTS: There
      were 96 eyes of 53 patients in the first data set, 36 (67.9%) were female and 17
      (32.1%) were male. There were 34 patients (61 eyes) in the High Myopia group and
      19 patients (35 eyes) in the Primary Pseudodrusen group. The mean age of the
      Primary Pseudodrusen group was 83.7 years and that of the High Myopia group was
      74.9 years, a difference that was significant (P < 0.001). Of the 61 eyes in the
      High Myopia group, only 3 (4.9%) had pseudodrusen and 0 had conventional drusen.
      In the Primary Pseudodrusen group, all had pseudodrusen by definition, but 28
      (80%) also had conventional drusen. The mean subfoveal choroidal thickness was
      181.7 MUm (median, 147; interquartile range, 65-225 MUm) in the Primary
      Pseudodrusen group and 59 MUm (median, 36; interquartile range, 21-90 MUm) in the
      myopic group. Generalized estimating equation analysis showed that eyes with
      pseudodrusen had thicker subfoveal choroidal thickness than eyes without, a
      result driven by the High Myopia group. In the second set of data, while the
      absolute number of eyes with pseudodrusen had a choroidal thickness between 201
      MUm and 250 MUm, the proportion with pseudodrusen was higher in eyes with thinner
      choroids, with a broad peak between 50 MUm and 100 MUm. CONCLUSION: Our results
      are not consistent with a simple cause or consequence relationship between
      pseudodrusen and choroidal thinning, but rather with a third yet unknown factor
      impacting both the pseudodrusen appearance and the choroidal thinning in
      susceptible populations. The reasons for the relative lack of drusen and
      pseudodrusen formation in high myopes need to be ascertained.

PMID- 24732698
TI  - Angiographic evidence of retinal artery transient occlusion in paracentral acute
      middle maculopathy.

PMID- 24732699
TI  - Epiretinal proliferation seen in association with lamellar macular holes: a
      distinct clinical entity.
AB  - PURPOSE: To describe the prevalence and imaging characteristics of a distinct
      entity of epiretinal proliferation seen predominantly in association with
      lamellar macular holes (LMH), termed lamellar hole-associated epiretinal
      proliferation (LHEP). METHODS: Retrospective observational case review of 2,030
      eyes of 1,104 patients with diagnoses including LMH, full-thickness macular hole,
      and epiretinal membrane (ERM) imaged with spectral domain optical coherence
      tomography (SD-OCT) from 2008 to 2013. Lamellar hole-associated epiretinal
      proliferation, defined on SD-OCT imaging as an epiretinal material of homogenous
      medium reflectivity, was identified and its features were qualitatively compared
      against conventional ERM using the SD-OCT data. RESULTS: Lamellar hole-associated
      epiretinal proliferation was found in 68 of 2,030 eyes (3.3%), of which 88.2% had
      LMH and 11.8% had full-thickness macular hole. Lamellar hole-associated
      epiretinal proliferation was found in 60 of 197 eyes (30.5%) with LMH and 8 of 99
      eyes (8.0%) with full-thickness macular hole. Lamellar hole-associated epiretinal
      proliferation was not seen in 1,734 eyes with ERM, which had no inner retinal
      defects detectable on SD-OCT. Lamellar hole-associated epiretinal proliferation
      appeared as a substantial material of homogenous medium reflectivity on the
      epiretinal surface that demonstrated contiguity with the middle retinal layers
      and conformed to the adjacent retinal anatomy. Of the eyes with LHEP and LMH, 98%
      had splitting of the retina in the region of Henle's fiber layer in the area
      immediately around the partial thickness hole, whereas 88% had visible connecting
      tissue from the base of the lamellar hole to the proliferating epiretinal tissue.
      In contrast to ERM, LHEP did not induce tractional effects such as distortion or
      edema of the underlying normal retinal tissue. Morphologic stability was
      demonstrated in 97% of eyes containing LHEP in serial eye-tracked SD-OCT images
      for up to 63 months of retrospective follow-up. CONCLUSION: Spectral domain
      optical coherence tomography imaging showed that a subset of patients with LMH
      had an epiretinal proliferation with medium reflectivity and no evidence of
      contractile properties that was contiguous with layers of the mid-retina. This
      phenotype differs from conventionally described ERMs in appearance and induced
      changes of the underlying retina. Given these distinct anatomical relationships,
      the presence of LHEP could affect surgical outcomes.

PMID- 24732700
TI  - Anatomic variations of the intrahepatic bile ducts: analysis of magnetic
      resonance cholangiopancreatography in 1011 consecutive patients.
AB  - OBJECTIVES: The aim of the study was to evaluate the frequency of anatomic
      variations of the hepatic duct bifurcation using magnetic resonance
      cholangiopancreatography (MRCP). METHODS: A total of 1,160 consecutive patients,
      referred to our department for MRCP due to suspected pancreatobiliary disease or
      before liver transplantation, were reviewed retrospectively. A total of 149
      patients with less than optimal results due to imaging limitations or secondary
      differentiations of bile duct anatomy were excluded from the study. The final
      study population was composed of 1,011 cases. RESULTS: Of the 1,160 patients, 149
      were excluded from the analysis. Typical biliary anatomy was observed in 79.4% of
      cases, but female potential living liver donors more frequently presented an
      anatomic variation. Typical anatomy was present in 75.7% of the females and 85.3%
      of the males (p < 0.05). Out of the remaining 1,011 patients, 208 (20.57%) were
      diagnosed with different levels of various anatomic variations of the intra- and
      extrahepatic biliary ducts. Of the 208 cases with diagnosed variations, 204
      (98.07%) and 4 (1.92%) turned out to have 1 and 2 different variations,
      respectively. The trifurcation variant was observed in 81 cases (8.01%), while 73
      subjects (7.23%) had an aberrant right biliary duct draining into the common
      hepatic duct. A right dorsocaudal branch draining into the left hepatic duct was
      present in 42 cases (4.15%). Four cases (0.4%) had 2 different variations and 8
      (0.8%) had uncommon anatomic variations. CONCLUSIONS: Typical intrahepatic
      biliary anatomy is present in about 80% of the inhabitants of the Aegean region
      of Turkey, but anatomic variants seem to be more frequent in females as compared
      to males. Trifurcation was the most common anatomic variation in our study
      population. The presence of an aberrant right hepatic duct emptying into the
      common hepatic duct was the second most common observation amongst our findings.

PMID- 24732701
TI  - A paradoxical pattern of indoleamine 2,3-dioxygenase expression in the colon
      tissues of patients with acute graft-versus-host disease.
AB  - Indoleamine 2,3-dioxygenase (IDO) is a rate-limiting enzyme for tryptophan
      catabolism that plays an important role in the induction of immune tolerance. It
      is induced in the colon and exerts its effects there, regulating T-cell
      proliferation and survival. To address the role of IDO in acute graft-versus-host
      disease (AGVHD) after human allogeneic hematopoietic stem cell transplantation,
      we analyzed the relationship between IDO expression in colon tissues and clinical
      outcomes among 41 AGVHD patients who were diagnosed as gut AGVHD by a colon
      mucosal biopsy within 100 days posttransplantation. By in situ
      immunohistochemical analyses, IDO expression was measured in colon mucosal
      mononuclear cells (MNCs) and endothelial cells (ECs) in GVHD areas. High IDO
      expression in MNCs and low IDO expression in ECs had a trend toward a lower
      nonrelapse mortality (p = 0.157 and p = 0.062, respectively). Multivariate
      analysis showed that high MNC combined with low EC IDO expression (p = 0.046), as
      well as low disease risk (p = 0.012), are associated with lower nonrelapse
      mortality. Paradoxical upregulation of IDO expression in colon MNCs and ECs may
      represent a new predictive factor for prognosis in gut AGVHD after human
      allogeneic hematopoietic stem cell transplantation.

PMID- 24732702
TI  - Barriers to chimerism after major histocompatibility complex-mismatched stem cell
      transplantation: a potential role for heterologous immunity.
AB  - The induction of mixed hematopoietic chimerism following allogeneic stem cell
      transplantation is a potential treatment modality for numerous nonmalignant
      diseases and generates a robust state of donor-specific tolerance. However,
      despite several promising results in murine studies, the translation to nonhuman
      primate models and clinical trials has proven to be more difficult. In contrast
      to specific pathogen-free bred laboratory mice, the immune system of humans has
      been in repeated contact with numerous pathogens, resulting in a broad memory-T
      cell repertoire. Crossreactivity of the virus-specific memory-T-cell pool against
      alloantigens has been described in a phenomenon called heterologous immunity. In
      this study, we demonstrate, in a murine stem cell transplantation model, that
      heterologous immunity is likely to be an important barrier for the induction of
      mixed hematopoietic chimerism after immunologic conditioning in the absence of
      cytoreduction. Additional T-cell depletion or a brief cyclosporine treatment can
      be applied to overcome the barrier of heterologous immunity. 

PMID- 24732704
TI  - Water is a molecular liquid.
AB  - Science and society are failing to grapple with the public health burden of
      cancer. In this short perspective piece, I contrast reductionism and complexity
      in cancer research, using water as a simple example, arguing for more
      'ecological' approaches to cancer. This is a call to arms to physical scientists,
      ecologists and others to get involved, to link up with cancer clinicians and
      cancer biologists, and an appeal to funding agencies to link up across
      disciplines to make a difference. 

PMID- 24732703
TI  - Activation of AMPKalpha2 is not crucial for mitochondrial uncoupling-induced
      metabolic effects but required to maintain skeletal muscle integrity.
AB  - Transgenic (UCP1-TG) mice with ectopic expression of UCP1 in skeletal muscle (SM)
      show a phenotype of increased energy expenditure, improved glucose tolerance and
      increase substrate metabolism in SM. To investigate the potential role of
      skeletal muscle AMPKalpha2 activation in the metabolic phenotype of UCP1-TG mice
      we generated double transgenic (DTG) mice, by crossing of UCP1-TG mice with DN
      AMPKalpha2 mice overexpressing a dominant negative alpha2 subunit of AMPK in SM
      which resulted in an impaired AMPKalpha2 activity by 90+/-9% in SM of DTG mice.
      Biometric analysis of young male mice showed decreased body weight, lean and fat
      mass for both UCP1-TG and DTG compared to WT and DN-AMPKalpha2 mice. Energy
      intake and weight-specific total energy expenditure were increased, both in UCP1
      TG and DTG mice. Moreover, glucose tolerance, insulin sensitivity and fatty acid
      oxidation were not altered in DTG compared to UCP1-TG. Also uncoupling induced
      induction and secretion of fibroblast growth factor 21 (FGF21) from SM was
      preserved in DTG mice. However, voluntary physical cage activity as well as ad
      libitum running wheel access during night uncovered a severe activity intolerance
      of DTG mice. Histological analysis showed a progressive degenerative morphology
      in SM of DTG mice which was not observed in SM of UCP1-TG mice. Moreover, ATP
      depletion related cellular stress response via heat shock protein 70 was highly
      induced, whereas capillarization regulator VEGF was suppressed in DTG muscle. In
      addition, AMPKalpha2-mediated induction of mitophagy regulator ULK1 was
      suppressed in DTG mice, as well as mitochondrial respiratory capacity and
      content. In conclusion, we demonstrate that AMPKalpha2 is dispensable for SM
      mitochondrial uncoupling induced metabolic effects on whole body energy balance,
      glucose homeostasis and insulin sensitivity. But strikingly, activation of
      AMPKalpha2 seems crucial for maintaining SM function, integrity and the ability
      to compensate chronic metabolic stress induced by SM mitochondrial uncoupling. 

PMID- 24732705
TI  - The missing link between clinical states and biomarkers in mental disorders.
AB  - Current diagnostic definitions of psychiatric disorders based on collections of
      symptoms encompass very heterogeneous populations and are thus likely to yield
      spurious results when exploring biological correlates of mental disturbances. It
      has been suggested that large studies of biomarkers across diagnostic entities
      may yield improved clinical information. Such a view is based on the concept of
      assessment as a collection of symptoms devoid of any clinical judgment and
      interpretation. Yet, important advances have been made in recent years in
      clinimetrics, the science of clinical judgment. The current clinical taxonomy in
      psychiatry, which emphasizes reliability at the cost of clinical validity, does
      not include effects of comorbid conditions, timing of phenomena, rate of
      progression of an illness, responses to previous treatments, and other clinical
      distinctions that demarcate major prognostic and therapeutic differences among
      patients who otherwise seem to be deceptively similar since they share the same
      psychiatric diagnosis. Clinimetrics may provide the missing link between clinical
      states and biomarkers in psychiatry, building pathophysiological bridges from
      clinical manifestations to their neurobiological counterparts.

PMID- 24732706
TI  - Acidification of floodplains due to river level decline during drought.
AB  - A severe drought from 2007 to 2010 resulted in the lowest river levels (1.75 m
      decline from average) in over 90 years of records at the end of the Murray
      Darling Basin in South Australia. Due to the low river level and inability to
      apply irrigation, the groundwater depth on the adjacent agricultural flood plain
      also declined substantially (1-1.5 m) and the alluvial clay subsoils dried and
      cracked. Sulfidic material (pH>4, predominantly in the form of pyrite, FeS2) in
      these subsoils oxidised to form sulfuric material (pH<4) over an estimated 3300
      ha on 13 floodplains. Much of the acidity in the deeply cracked contaminated soil
      layers was in available form (in pore water and on cation exchange sites), with
      some layers having retained acidity (iron oxyhydroxysulfate mineral jarosite).
      Post drought, the rapid raising of surface and ground water levels mobilised
      acidity in acid sulfate soil profiles to the floodplain drainage channels and
      this was transported back to the river via pumping. The drainage water exhibited
      low pH (2-5) with high soluble metal (Al, Co, Mn, Fe, Mn, Ni, and Zn)
      concentrations, in exceedance of guidelines for ecosystem protection. Irrigation
      increased the short-term transport of acidity, however loads were generally
      greater in the non-irrigation (winter) season when rainfall is highest (0.0026
      tonnes acidity/ha/day) than in the irrigation (spring-summer) season (0.0013
      tonnes acidity/ha/day). Measured reductions in groundwater acidity and increases
      in pH have been observed over time but severe acidification persisted in
      floodplain sediments and waters for over two years post-drought. Results from 2
      dimensional modelling of the river-floodplain hydrological processes were
      consistent with field measurements during the drying phase and illustrated how
      the declining river levels led to floodplain acidification. A modelled management
      scenario demonstrated how river level stabilisation and limited irrigation could
      have prevented, or greatly lessened the severity of the acidification.

PMID- 24732707
TI  - Cultivation of Candida sp. LEB-M3 in glycerol: lipid accumulation and prediction
      of biodiesel quality parameters.
AB  - The quality of biodiesel from lipids produced by the yeast Candida sp. LEB-M3 was
      predicted, by the use of mathematical models for parameters that specify quality
      as a function of the fatty acid profile. The lipid production was studied
      according to the experimental design methodology, for different cultivation
      conditions for agitation and aeration. Lipid compositions were affected by the
      cultivation conditions, and the agitation presented a positive effect for the
      formation of monounsaturated fatty acids and negative effect for saturated fatty
      acids. Aeration had a positive effect on the formation of polyunsaturated fatty
      acids. According to the predictions by the mathematical models, the cetane number
      varied from 61 to 67, the oxidative stability from 11 to 17h, the iodine index
      from 55 to 75gI2/100g, density from 852 to 868kg/m(3). All cultivation conditions
      led to lipid compositions, whose predicted bioparameter values indicate that
      biodiesel from this lipid source should present current standard quality. 

PMID- 24732708
TI  - A Case of IgG4-Related Retroperitoneal Fibrosis from the Renal Pelvis Mimicking
      Bilateral Hydronephrosis.
AB  - We describe a 49-year-old woman who presented with continuous bilateral lumbago.
      As the patient's ultrasonography manifestations were very similar to those of
      bilateral hydronephrosis, we performed retrograde pyelography and ureteroscopy.
      However, apart from slight left ureteropelvic junction obstruction, there was no
      hydronephrosis. Since malignant disease could not be completely denied, computed
      tomography-guided biopsy was performed. However, the tissue did not show evidence
      of malignancy. As the patient continued to have lumbago, we measured serum IgG4
      levels because of suspicion of retroperitoneal fibrosis secondary to IgG4-related
      disease, which proved to be high. Further, immunostaining of the renal pelvic
      biopsy samples showed IgG4-positive cells. Therefore, diagnosing IgG4-related
      retroperitoneal fibrosis, we administered corticosteroids. The patient responded
      favorably to the drug, with gradual regression of the lesion. 

PMID- 24732710
TI  - Autophagy protects against senescence and apoptosis via the RAS-mitochondria in
      high-glucose-induced endothelial cells.
AB  - BACKGROUNDS: Autophagy is an important process in the pathogenesis of diabetes
      and plays a critical role in maintaining cellular homeostasis. However, the
      autophagic response and its mechanism in diabetic vascular endothelium remain
      unclear. METHODS AND RESULTS: We studied high-glucose-induced renin-angiotensin
      system (RAS)-mitochondrial damage and its effect on endothelial cells. With
      regard to therapeutics, we investigated the beneficial effect of angiotensin
      converting enzyme inhibitors (ACEIs) or angiotensin II type 1 receptor blockers
      (ARBs) against high-glucose-induced endothelial responses. High glucose activated
      RAS, enhanced mitochondrial damage and increased senescence, apoptosis and
      autophagic-responses in endothelial cells, and these effects were mimicked by
      using angiotensin II (Ang). The use of an ACEI or ARB, however, inhibited the
      negative effects of high glucose. Direct mitochondrial injury caused by carbonyl
      cyanide 3-chlorophenylhydrazone (CCCP) resulted in similar negative effects of
      high glucose or Ang and abrogated the protective effects of an ACEI or ARB.
      Additionally, by impairing autophagy, high-glucose-induced senescence and
      apoptosis were accelerated and the ACEI- or ARB-mediated beneficial effects were
      abolished. Furthermore, increases in FragELTM DNA Fragmentation (TUNEL)-positive
      cells, beta-galactosidase activation and the expression of autophagic biomarkers
      were revealed in diabetic patients and rats, and the treatment with an ACEI or
      ARB decreased these responses. CONCLUSIONS: These data suggest that autophagy
      protects against senescence and apoptosis via RAS-mitochondria in high-glucose
      induced endothelial cells.

PMID- 24732709
TI  - Reversal of tumor immune inhibition using a chimeric cytokine receptor.
AB  - The success of adoptively transferred tumor-directed T cells requires them to
      survive and expand in vivo. Most tumors, however, employ immune evasion
      mechanisms, including the production of inhibitory cytokines that limit in vivo T
      cell persistence and effector function. To protect tumor-directed T cells from
      such negative influences, we generated a chimeric cytokine receptor in which the
      interleukin (IL) 4 receptor exodomain was fused to the IL7 receptor endodomain.
      We thereby inverted the effects of tumor-derived IL4 so that the proliferation
      and activation of tumor directed cytotoxic T cells was enhanced rather than
      inhibited in the tumor microenvironment, resulting in superior antitumor
      activity. These transgenic T cells were only activated in the tumor environment
      since triggering required exposure to both tumor antigen (signal 1) and tumor
      derived IL4 (signal 2). This selectivity supports future clinical adaptation. 

PMID- 24732712
TI  - Plant autophagy is responsible for peroxisomal transition and plays an important
      role in the maintenance of peroxisomal quality.
AB  - In photosynthetic cells, a large amount of hydrogen peroxide is produced in
      peroxisomes through photorespiration, which is a metabolic pathway related to
      photosynthesis. Hydrogen peroxide, a reactive oxygen species, oxidizes
      peroxisomal proteins and membrane lipids, resulting in a decrease in peroxisomal
      quality. We demonstrate that the autophagic system is responsible for the
      elimination of oxidized peroxisomes in plant. We isolated Arabidopsis mutants
      that accumulated oxidized peroxisomes, which formed large aggregates. We revealed
      that these mutants were defective in autophagy-related (ATG) genes and that the
      aggregated peroxisomes were selectively targeted by the autophagic machinery.
      These findings suggest that autophagy plays an important role in the quality
      control of peroxisomes by the selective degradation of oxidized peroxisomes. In
      addition, the results suggest that autophagy is also responsible for the
      functional transition of glyoxysomes to leaf peroxisomes.

PMID- 24732711
TI  - Cellular processing of myocilin.
AB  - BACKGROUND: Myocilin (MYOC) is a gene linked directly to juvenile- and adult
      onset open angle glaucoma. Mutations including Pro370Leu (P370L) and Gln368stop
      (Q368X) have been identified in patients. In the present study, we investigated
      the processing of myocilin in human trabecular meshwork (TM) cells as well as in
      inducible, stable RGC5 cell lines. METHODOLOGY/PRINCIPAL FINDINGS: The turnover
      and photoactivation experiments revealed that the endogenous myocilin in human
      trabecular meshwork (TM) cells was a short-lived protein. It was found that the
      endogenous myocilin level in TM cells was increased by treatment of lysosomal and
      proteasomal inhibitors, but not by autophagic inhibitor. Multiple bands
      immunoreactive to anti-ubiquitin were seen in the myocilin pull down, indicating
      that myocilin was ubiquitinated. In inducible cell lines, the turnover rate of
      overexpressed wild-type and mutant P370L and Q368X myocilin-GFP fusion proteins
      was much prolonged. The proteasome function was compromised and autophagy was
      induced. A decreased PSMB5 level and an increased level of autophagic marker,
      LC3, were demonstrated. CONCLUSIONS/SIGNIFICANCE: The current study provided
      evidence that in normal homeostatic situation, the turnover of endogenous
      myocilin involves ubiquitin-proteasome and lysosomal pathways. When myocilin was
      upregulated or mutated, the ubiquitin-proteasome function is compromised and
      autophagy is induced. Knowledge of the degradation pathways acting on myocilin
      can help in design of novel therapeutic strategies for myocilin-related glaucoma.

PMID- 24732713
TI  - Diagnostic effectiveness of dynamic colpocystoproctography in women planning for
      combined surgery with urinary incontinence and pelvic organ prolapse.
AB  - OBJECTIVE: To evaluate the advantage of performing the dynamic cystoproctography
      (DCP) in patients planning for combined surgery due to urinary incontinence and
      pelvic organ prolapse (POP). MATERIALS AND METHODS: We performed DCP on a total
      of 113 consecutive women with POP and compared the findings of the physical
      examination with POP quantification against those of DCP including squeezing,
      straining and evacuation phases, and analyzed the changes to the rates of
      surgical planning. For statistical analysis, sensitivity, specificity, and
      positive predictive value of each test were performed. RESULTS: DCP identified an
      additional 10 cases of cystocele, 32 cases of rectocele, 2 cases of enterocele, 4
      cases of sigmoidocele, and 8 cases of rectal intussusception compared to those
      cases who were only included for a physical examination. The initial surgical
      plan was changed in a total of 24 cases (22.1%). The prevalence of bowel symptoms
      in the group in which the surgical plan changed was higher than in the group with
      no changes to the surgical plan (p = 0.023). CONCLUSIONS: DCP may be a more
      sensitive test for diagnosing POP compared to physical examination alone, and it
      is useful to patients with bowel symptoms by making surgical planning for
      combined surgery with stress urinary incontinence and POP.

PMID- 24732714
TI  - Fetuin A as a new marker of inflammation in Hashimoto thyroiditis.
AB  - AIM: Fetuin-A levels are reported to be low as a negative acute phase reactant in
      systemical inflammatory situations. Hashimoto thyroiditis is characterized with
      inflammation. In this study, we hypothesised that the serum fetuin A levels could
      be found to be low due to inflammation in patients with Hashimoto thyroiditis.
      For this purpose, serum fetuin A levels in patients with Hashimoto thyroiditis
      were compared with those in healthy subjects. METHODS: A total of 85 participants
      (11 male, 74 female, mean age: 38.60+/-10.14 years) were included. The patient
      group consisted of 44 Hashimoto thyroiditis patients with subclinical
      hypothyroidism (7 male, 37 female) and the control group consisted of 41 healthy
      subjects (4 male, 37 female). Groups were compared according to their
      demographic, anthropometric and biochemical data and serum fetuin-A levels.
      Correlation analysis was used for determining the relation between fetuin A
      levels and clinical parameters. RESULTS: Fetuin-A levels of the patient group
      were found lower than those of the control group (0.58+/-0.50 g/L versus 1.53+/
      1.60 g/L, P=0.001). Fetuin-A levels were not correlated with clinical parameters
      such as TSH, C-reactive protein, body mass index, waist circumference, blood
      pressure, glucose, and lipids. CONCLUSION: These findings supported the
      hypothesis that serum fetuin A levels could be found to be low as a negative
      acute phase reactant in patients with Hashimoto thyroiditis. Fetuin A can be
      considered as an indicator of inflammation in Hashimoto thyroiditis.

PMID- 24732715
TI  - Improving long-term prediction of first cardiovascular event: the contribution of
      family history of coronary heart disease and social status.
AB  - OBJECTIVE: The aim of this study is to assess whether family history of coronary
      heart disease (CHD) and education as proxy of social status improve long-term
      cardiovascular disease risk prediction in a low-incidence European population.
      METHODS: The 20-year risk of first coronary or ischemic stroke events was
      estimated using sex-specific Cox models in 3956 participants of three population
      based surveys in northern Italy, aged 35-69 years and free of cardiovascular
      disease at enrollment. The additional contribution of education and positive
      family history of CHD was defined as change in discrimination and Net
      Reclassification Improvement (NRI) over the model including 7 traditional risk
      factors. RESULTS: Kaplan-Meier 20-year risk was 16.8% in men (254 events) and
      6.4% in women (102 events). Low education (hazard ratio=1.35, 95%CI 0.98-1.85)
      and family history of CHD (1.55; 1.19-2.03) were associated with the endpoint in
      men, but not in women. In men, the addition of education and family history
      significantly improved discrimination by 1%; NRI was 6% (95%CI: 0.2%-15.2%),
      raising to 20% (0.5%-44%) in those at intermediate risk. NRI in women at
      intermediate risk was 7%. CONCLUSION: In low-incidence populations, family
      history of CHD and education, easily assessed in clinical practice, should be
      included in long-term cardiovascular disease risk scores, at least in men.

PMID- 24732716
TI  - Human papillomavirus vaccine acceptability among parents of adolescent girls:
      obstacles and challenges in Mysore, India.
AB  - OBJECTIVE: Worldwide, 530,000 women are diagnosed with cervical cancer and
      275,000 die annually. India bears the greatest burden of the disease with 132,000
      cases and 74,000 deaths yearly. Widespread uptake of human papillomavirus (HPV)
      vaccine could reduce incidence and mortality by two-thirds. This study explored
      obstacles and facilitators of parental acceptability of HPV vaccine. METHODS: In
      2010, questionnaires were sent home with a random sample of 800 girls attending
      12 schools in Mysore city to be completed by a parent. Data were analyzed using
      multivariable logistic regression with generalized estimating equation to account
      for potential clustering by school. RESULTS: Of the 797 completed surveys; 71%
      reported willingness to accept HPV vaccine for their daughters. The adjusted odds
      of acceptance was higher among participants who received recommendation from
      their parents, perceived cervical cancer as a serious disease, believed that HPV
      vaccine was safe, or felt that vaccination was a good way to protect against
      cervical cancer. Parents who had concerns about vaccine side-effects or thought
      that it would cause pain had lower odds of acceptance. CONCLUSION: Future
      promotion of vaccine should emphasize safety of immunization and involve
      promotion to the extended family, so that they actively recommend immunization of
      young adolescent girls.

PMID- 24732717
TI  - Urban sprawl and body mass index among displaced Hurricane Katrina survivors.
AB  - OBJECTIVE: Existing research suggests that walkable environments are protective
      against weight gain, while sprawling neighborhoods may pose health risks. Using
      prospective data on displaced Hurricane Katrina survivors, we provide the first
      natural experimental data on sprawl and body mass index (BMI). METHODS: The
      analysis uses prospectively collected pre- (2003-2005) and post-hurricane (2006
      2007) data from the Resilience in Survivors of Katrina (RISK) project on 280
      displaced Hurricane Katrina survivors who had little control over their
      neighborhood placement immediately after the disaster. The county sprawl index, a
      standardized measure of built environment, was used to predict BMI at follow-up,
      adjusted for baseline BMI and sprawl; hurricane-related trauma; and demographic
      and economic characteristics. RESULTS: Respondents from 8 New Orleans-area
      counties were dispersed to 76 counties post-Katrina. Sprawl increased by an
      average of 1.5 standard deviations (30 points) on the county sprawl index. Each
      one point increase in sprawl was associated with approximately .05kg/m(2) higher
      BMI in unadjusted models (95%CI: .01-.08), and the relationship was not
      attenuated after covariate adjustment. CONCLUSIONS: We find a robust association
      between residence in a sprawling county and higher BMI unlikely to be caused by
      self-selection into neighborhoods, suggesting that the built environment may
      foster changes in weight.

PMID- 24732718
TI  - A repeated cross-sectional study examining the school impact on child weight
      status.
AB  - OBJECTIVE: The aim of this study is to examine whether there is a differential
      impact of primary schools upon children's weight status. METHODS: A repeated
      cross-sectional study was undertaken using five years (2006/07-2010/11) of
      National Child Measurement Programme data, comprising 57,976 children (aged 4-5
      (Reception) and 10-11 (Year 6) years) from 300 primary schools across Devon,
      England. Examining each year separately, the schools were ranked according to
      their observed and residual (having accounted for school and neighbourhood
      clustering and pupil ethnicity and socioeconomic status) school mean body mass
      index standard deviation score (BMI-SDS). Subtracting the Reception from the Year
      6 mean residuals gave 'value-added' scores for each school which were also
      ranked. The rankings were compared within and across the years to assess
      consistency. RESULTS: Although pupil BMI-SDS was high, >97% of the variation in
      BMI-SDS was attributable to environments other than the school. The 'value-added'
      by each school was only poorly correlated with the observed and residual pupil
      BMI-SDS; but none of the rankings were consistent across the five years.
      CONCLUSION: The inconsistency of the rankings and the small variation in BMI-SDS
      at the level of the school suggests that there is no systematic differential
      impact of primary schools upon pupil weight status.

PMID- 24732719
TI  - Patterns of sedentary time and cardiometabolic risk among Canadian adults.
AB  - OBJECTIVE: The aim of this study is to examine the associations of total
      sedentary time and patterns of sedentary time with cardiometabolic biomarkers in
      a large representative sample of Canadian adults. METHODS: The study is based on
      4935 adults aged 20-79years, from the 2007/09 and 2009/11 Canadian Health
      Measures Survey. Total sedentary time, patterns of sedentary time (>=20minute
      prolonged sedentary bouts, number of sedentary breaks), and moderate- to vigorous
      intensity physical activity (MVPA) were accelerometer-derived. Waist
      circumference, systolic and diastolic blood pressure, high-density lipoprotein
      (HDL) cholesterol, and C-reactive protein were measured. Triglycerides, low
      density lipoprotein (LDL) cholesterol, insulin, and glucose were also measured in
      a fasting sub-sample (n=2551). RESULTS: Total sedentary time and time in
      >=20minute prolonged sedentary bouts were associated with higher insulin and
      lower diastolic blood pressure levels (P<0.05). On average, each additional 10
      breaks/day was associated with 0.83 (95%CI: 1.35, 0.31) cm lower waist
      circumference, 0.32 (0.62, 0.02) mmHg lower systolic blood pressure, 0.01 (0.00,
      0.02) mmol/l higher HDL-cholesterol, 3.72 (1.34, 6.13) % lower triglycerides,
      0.57 (0.23, 0.92) % lower glucose, and 4.19 (1.80, 6.63) % lower insulin.
      CONCLUSION: These findings in a large representative sample of Canadian adults
      indicate that breaking up sedentary time may be particularly important for
      cardiometabolic health.

PMID- 24732720
TI  - Changes in food and beverage environments after an urban corner store
      intervention.
AB  - OBJECTIVE: In response to the obesity epidemic, interventions to improve the food
      environment in corner stores have gained attention. This study evaluated the
      availability, quality, and price of foods in Philadelphia corner stores before
      and after a healthy corner store intervention with two levels of intervention
      intensity ("basic" and "conversion"). METHODS: Observational measures of the food
      environment were completed in 2011 and again in 2012 in corner stores
      participating in the intervention, using the Nutrition Environment Measures
      Survey for Corner Stores (NEMS-CS). Main analyses included the 211 stores
      evaluated at both time-points. A time-by-treatment interaction analysis was used
      to evaluate the changes in NEMS-CS scores by intervention level over time.
      RESULTS: Availability of fresh fruit increased significantly in conversion stores
      over time. Specifically, there were significant increases in the availability of
      apples, oranges, grapes, and broccoli in conversion stores over time. Conversion
      stores showed a trend toward a significantly larger increase in the availability
      score compared to basic stores over time. CONCLUSION: Interventions aimed at
      increasing healthy food availability are associated with improvements in the
      availability of low-fat milk, fruits, and some vegetables, especially when
      infrastructure changes, such as refrigeration and shelving enhancements, are
      offered.

PMID- 24732721
TI  - Protective factors against depression during the transition from adolescence to
      adulthood: findings from a national Canadian cohort.
AB  - OBJECTIVE: This study sought to identify factors protective against the onset or
      recurrence of depression in early adulthood, and to describe their interactions
      with stressors during this transitional period. METHODS: 1137 members of Canada's
      National Population Health Survey were followed from ages 12 to 17 in 1994/95 and
      contacted every two years until 2008/09. Protective factors measured at age 16/17
      included social support, physical activity, mastery, self-esteem, and education
      level. General linear mixed models were used to examine the relationship between
      the protective factors and five assessments of depression, including interactions
      between protective factors and four types of stress: stressful life events, and
      work, financial, and personal stress. RESULTS: High mastery in adolescence had a
      significant protective effect against depression in early adulthood. Participants
      with high social support in adolescence were significantly less likely to become
      depressed after experiencing work or financial stress, compared to those with low
      social support. Those who were physically active in adolescence were less likely
      to become depressed after experiencing work stress, and higher overall education
      level reduced depression risk following personal stress or major life events.
      CONCLUSION: Social support and physical activity may be ideal targets for school
      based depression interventions during a potentially stressful transitional
      period.

PMID- 24732722
TI  - Objectively measured physical activity and inflammatory cytokine levels in middle
      aged Japanese people.
AB  - OBJECTIVE: Studies using self-reported physical activity (PA) showed that higher
      PA is associated with lower circulating levels of C-reactive protein; in
      contrast, studies investigating associations of objective PA and other
      inflammatory markers are limited. We investigated cross-sectional associations of
      accelerometer-determined PA with circulating levels of myokine-type inflammatory
      cytokines in a middle-aged Japanese population. METHOD: A total of 1838
      individuals (737 men and 1101 women) aged 40 to 69 years participated in the
      baseline survey of a population-based cohort study in Saga, Japan (2005-2007).
      Habitual PA was assessed by a single-axis accelerometer. Serum interleukin (IL)
      4, IL-6, IL-8, IL-15, and tumor necrosis factor (TNF)-alpha were measured by a
      multiplex enzyme-linked immunosorbent assay. Associations between PA and cytokine
      levels were assessed by multiple regression analysis and analysis of covariance,
      with adjustment for potential confounders. RESULTS: Step count and PA level (PAL)
      were inversely associated with TNF-alpha and IL-15 even after adjusting for BMI.
      Similarly, greater PA indices were also independently associated with a lower
      level of inflammatory cytokine z score as an index of overall inflammation.
      CONCLUSION: The current results suggest that greater engagement in daily PA may
      be linked with reduced levels of myokine-type cytokines including IL-15,
      irrespective of body weight in middle-aged Japanese people.

PMID- 24732723
TI  - Epidemiology and outcomes associated with anemia during long-term support with
      continuous-flow left ventricular assist devices.
AB  - BACKGROUND: The purpose of this study was to define the prevalence and clinical
      ramifications of anemia in patients implanted with a continuous-flow left
      ventricular assist device (CF-LVAD). METHODS AND RESULTS: Patients implanted with
      a CF-LVAD from January 1, 2008, to April 30, 2012, were included in this
      retrospective cohort study. The primary outcome was the prevalence of anemia
      throughout the 1st year of device support. Secondary end points included the
      impact of anemia on rates of readmission to hospital and mortality. Ninety-one
      patients were included; the prevalence of anemia 360 days after implantation was
      significantly reduced compared with baseline (61.4% vs 79.1%, respectively; P =
      .032); 65.4% of anemic patients and 34.6% of nonanemic patients were readmitted
      at least once (P = .067). The median number of readmissions in the anemic
      compared with the nonanemic group was 4 (interquartile range [IQR] 2-6) versus
      1.5 (IQR 1-3), respectively (P < .001). Furthermore, among those who experienced
      >3 readmissions during the 1st year, 19 were anemic compared with 1 patient who
      was not anemic (P < .001). CONCLUSIONS: Anemia remains a prevalent condition
      while on CF-LVAD support and is associated with a significant increase in the
      number of hospital readmissions.

PMID- 24732725
TI  - Individualized proteomics.
AB  - Human individuals differ from one another in almost all of their genes due to
      single nucleotide polymorphisms (SNPs). When the maternal and the paternal
      genomes become combined in a F1 individual, the two alleles of each gene
      represent arbitrary combinations. In consequence, individuals show high
      variability in protein expression. Furthermore, within a proteome, the proteins
      form networks of protein-protein interactions. These networks differ between
      individuals in robustness against genetic or/and environmental perturbation due
      to polymorphisms, which differ in type and composition between individuals, and
      modify the arrangement of proteins in the proteomic network. As a general
      conclusion, the robustness of a human individual against diseases may depend on
      the structure and expression of the protein-protein interaction network that
      varies in its functional efficiency between individuals due to "network
      polymorphisms". This article is part of a Special Issue entitled: 20years of
      Proteomics in memory of Viatliano Pallini. Guest Editors: Luca Bini, Juan J.
      Calvete, Natacha Turck, Denis Hochstrasser and Jean-Charles Sanchez. 

PMID- 24732724
TI  - Torsion and antero-posterior bending in the in vivo human tibia loading regimes
      during walking and running.
AB  - Bending, in addition to compression, is recognized to be a common loading pattern
      in long bones in animals. However, due to the technical difficulty of measuring
      bone deformation in humans, our current understanding of bone loading patterns in
      humans is very limited. In the present study, we hypothesized that bending and
      torsion are important loading regimes in the human tibia. In vivo tibia segment
      deformation in humans was assessed during walking and running utilizing a novel
      optical approach. Results suggest that the proximal tibia primarily bends to the
      posterior (bending angle: 0.15 degrees -1.30 degrees ) and medial aspect (bending
      angle: 0.38 degrees -0.90 degrees ) and that it twists externally (torsion angle:
      0.67 degrees -1.66 degrees ) in relation to the distal tibia during the stance
      phase of overground walking at a speed between 2.5 and 6.1 km/h. Peak posterior
      bending and peak torsion occurred during the first and second half of stance
      phase, respectively. The peak-to-peak antero-posterior (AP) bending angles
      increased linearly with vertical ground reaction force and speed. Similarly, peak
      to-peak torsion angles increased with the vertical free moment in four of the
      five test subjects and with the speed in three of the test subjects. There was no
      correlation between peak-to-peak medio-lateral (ML) bending angles and ground
      reaction force or speed. On the treadmill, peak-to-peak AP bending angles
      increased with walking and running speed, but peak-to-peak torsion angles and
      peak-to-peak ML bending angles remained constant during walking. Peak-to-peak AP
      bending angle during treadmill running was speed-dependent and larger than that
      observed during walking. In contrast, peak-to-peak tibia torsion angle was
      smaller during treadmill running than during walking. To conclude, bending and
      torsion of substantial magnitude were observed in the human tibia during walking
      and running. A systematic distribution of peak amplitude was found during the
      first and second parts of the stance phase. 

PMID- 24732726
TI  - Analysis of initial changes in the proteins of soybean root tip under flooding
      stress using gel-free and gel-based proteomic techniques.
AB  - Flooding has a severe negative effect on soybean cultivation in the early stages
      of growth. To obtain a better understanding of the response mechanisms of soybean
      to flooding stress, initial changes in root tip proteins under flooding were
      analyzed using two proteomic techniques. Two-day-old soybeans were treated with
      flooding for 3, 6, 12, and 24h. The weight of soybeans increased during the first
      3h of flooding, but root elongation was not observed. Using gel-based and gel
      free proteomic techniques, 115 proteins were identified in root tips, of which 9
      proteins were commonly detected by both methods. The 71 proteins identified by
      the gel-free proteomics were analyzed by a hierarchical clustering method based
      on induction levels during the flooding, and the proteins were divided into 5
      clusters. Additional interaction analysis of the proteins revealed that ten
      proteins belonging to cluster I formed the center of a protein interaction
      network. mRNA expression analysis of these ten proteins showed that citrate lyase
      and heat shock protein 70 were down-regulated, whereas calreticulin was up
      regulated in initial phase of flooding. These results suggest that flooding
      stress to soybean induces calcium-related signal transduction, which might play
      important roles in the early responses to flooding. BIOLOGICAL SIGNIFICANCE:
      Flooding has a severe negative effect on soybean cultivation, particularly in the
      early stages of growth. To better understand the response mechanisms of soybean
      to the early stages of flooding stress, two proteomic techniques were used. Two
      day-old soybeans were treated without or with flooding for 3, 6, 12, and 24h. The
      fresh weight of soybeans increased during the first 3h of flooding stress, but
      the growth then slowed and no root elongation was observed. Using gel-based and
      gel-free proteomic techniques, 115 proteins were identified in root tips, of
      which 9 proteins were commonly detected by both methods. The 71 proteins
      identified by the gel-free proteomics were analyzed by a hierarchical clustering
      method based on induction levels during the flooding stress, and 5 protein
      clusters were recognized. Protein interaction analysis revealed that ten proteins
      belonging to cluster I formed the center of a protein interaction network. mRNA
      expression analysis of these ten proteins showed that citrate lyase and heat
      shock protein 70 were down-regulated in response to flooding stress, whereas
      calreticulin was up-regulated. These results suggest that flooding stress to
      soybean induces calcium-related signal transduction, which might play important
      roles in the early responses to flooding.

PMID- 24732727
TI  - Happy trails: the effect of a media campaign on urban trail use in southern
      Nevada.
AB  - BACKGROUND: Many Americans do not meet recommendations for physical activity
      (PA). Communities are building trail networks to encourage PA, but the
      relationship between trails and PA is not well understood. METHODS: We monitored
      usage of urban trails (N = 10) in Las Vegas, NV, before and after a promotional
      marketing campaign (October 2011 and April 2012). The media campaign featured
      print, online, and radio ads, as well as billboards and signage on gas pumps.
      Data were collected with infrared monitors that were placed on the trails for
      periods of 7 days. We compared preintervention and postintervention usage rates.
      RESULTS: Mean usage increased (P < .001) from 3.91 to 5.95 users per hour
      (52.17%) after the promotional campaign. We observed significant increases at 7
      individual trails, significant declines at 2 trails, and no change at 1 trail.
      CONCLUSION: Promotional campaigns may be an effective way to increase trail usage
      and encourage PA.

PMID- 24732728
TI  - Immature visual neural system in children reflected by contrast sensitivity with
      adaptive optics correction.
AB  - This study aimed to explore the neural development status of the visual system of
      children (around 8 years old) using contrast sensitivity. We achieved this by
      eliminating the influence of higher order aberrations (HOAs) with adaptive optics
      correction. We measured HOAs, modulation transfer functions (MTFs) and contrast
      sensitivity functions (CSFs) of six children and five adults with both corrected
      and uncorrected HOAs. We found that when HOAs were corrected, children and adults
      both showed improvements in MTF and CSF. However, the CSF of children was still
      lower than the adult level, indicating the difference in contrast sensitivity
      between groups cannot be explained by differences in optical factors. Further
      study showed that the difference between the groups also could not be explained
      by differences in non-visual factors. With these results we concluded that the
      neural systems underlying vision in children of around 8 years old are still
      immature in contrast sensitivity. 

PMID- 24732729
TI  - Trends in a life threatening condition: morbid obesity in dutch, Turkish and
      Moroccan children in The Netherlands.
AB  - BACKGROUND: Morbid obesity can be a life threatening condition. The aim of our
      study is to assess the trend in morbid obesity in The Netherlands among children
      of Dutch origin since 1980, and among children of Turkish and Moroccan origin
      since 1997. METHODS AND FINDINGS: Cross-sectional height and weight data of
      children of Dutch, Turkish and Moroccan origin aged 2-18 years were selected from
      three national Dutch Growth Studies performed in 1980, 1997 and 2009 (n =
      54,814). Extended international (IOTF) cut-offs in childhood were used to define
      morbid obesity (obesity class II and III combined). The morbidity index for
      overweight was calculated as the prevalence of morbid obesity divided by the
      prevalence of overweight. Our study showed that the prevalence of morbid obesity
      in children of Dutch origin was 0.59% in boys and 0.53% in girls in 2009.
      Significant upward trends occurred since 1980 and 1997. The prevalence was three
      to four fold higher in Turkish children compared to Dutch children. The Turkish
      children also had an upward trend since 1997, but this was only statistically
      significant in boys. The prevalence of morbid obesity in Moroccan children was
      two to three fold higher than in Dutch children, but it remained almost stable
      between 1997 and 2009. The Dutch and Turkish children showed an upward trend in
      morbidity index for overweight since respectively 1980 and 1997, while the
      Moroccan children showed a downward trend since 1997. In 2009, children of low
      educated parents had the highest prevalence rates of morbid obesity; 1.06% in
      Dutch, 2.11% in Turkish and 1.41% in Moroccan children. CONCLUSIONS AND
      SIGNIFICANCE: An upward trend of morbid obesity in Dutch and Turkish children in
      The Netherlands occurred. Monitoring and reducing the prevalence of childhood
      morbid obesity is of high importance for these children, health care and the
      community.

PMID- 24732733
TI  - Predictive factors for post-ERCP pancreatitis: a large-scale single expertized
      endoscopist study.
AB  - BACKGROUND: Pancreatitis remains the most common and feared complication of
      therapeutic endoscopic cholangiopancreatography (ERCP) associated with
      substantial morbidity. The patient-related and procedure-related independent risk
      factors for post-ERCP pancreatitis (PEP) in a large case volume by a single
      experienced endoscopist have been investigated only by few studies. The aim of
      the study was to investigate patient-related and procedure-related risk factors
      for PEP collected by a defined protocol on patients who underwent therapeutic
      ERCP in a single endoscopic unit during the last 8 years. PATIENTS AND METHODS:
      Our retrospective cohort study included a total of 2688 therapeutic ERCPs
      enrolled in the final analysis. The impact of the risk factors on PEP development
      was investigated by univariate and multivariate analysis. PEP was diagnosed and
      its severity was graded according to the consensus criteria. RESULTS: With the
      exception of history of pancreatitis, there was no other statistically
      significant difference of patients' characteristics between patients with and
      without PEP. Female sex, age, difficult cannulation, suspected sphincter of Oddi
      dysfunction, metal stent placement, opacification of main pancreatic duct, and
      suprapapillary fistulotomy were not found to be risk factors for PEP by
      univariate and multivariate analysis. Both univariate and multivariate analysis
      showed history of acute pancreatitis, needle-knife papillotomy, transpancreatic
      sphincterotomy, opacification of first-class and second-class pancreatic
      ductules, and acinarization as independent risk factors for PEP. CONCLUSIONS:
      History of acute pancreatitis, needle-knife papillotomy, transpancreatic
      sphincterotomy, opacification of first-class and second-class pancreatic
      ductules, and acinarization were all identified as independent risk factors for
      PEP.

PMID- 24732734
TI  - Surgical results of laparoscopic Roux-en-Y gastric bypass in super obese patients
      with BMI>=60 in China.
AB  - PURPOSE: Bariatric surgery in mainland China is still in its initial stages. The
      aim of this study was to investigate the feasibility and efficacy of laparoscopic
      Roux-en-Y gastric bypass (LRYGB) for Chinese super obese patients with body mass
      index (BMI) >=60 kg/m. METHODS: Twenty-six super obese patients underwent LRYGB,
      performed by a single surgeon, at the First Affiliated Hospital of Jinan
      University between June 2004 and September 2012. Surgical outcomes were analyzed
      retrospectively. RESULTS: All 26 LRYGB procedures were performed successfully,
      with no conversion to open surgery. Preoperative mean body weight and BMI were
      192.3 kg and 65.8 kg/m, respectively. Mean percentage of excess weight loss in
      the 12 months after surgery was 55.3+/-7.6%. Obesity-related comorbidities
      improved significantly. Two patients experienced perioperative complications, 1
      with respiratory failure and 1 with umbilical wound infection. Six patients
      developed long-term complications, but all were cured by conservative treatment.
      CONCLUSIONS: Chinese obese population is unique in diet, lifestyle, sex, age, and
      geographical differences. LRYGB is feasible for Chinese super obese patients,
      with significant short-term results. Further observations are required to assess
      long-term outcomes.

PMID- 24732735
TI  - One-port videothoracoscopic surgical intervention.
AB  - BACKGROUND: One-port video-assisted thoracic surgery (VATS) has recently been
      proposed as an alternative to conventional 3-port VATS. To reduce pain, chest
      wall paresthesia, and hospital stay, lesser ports are the current direction.
      MATERIALS AND METHODS: From 2007 to 2010, 98 patients underwent 1-port VATS
      procedure. The charts were retrospectively evaluated. A 2.5 cm long incision was
      made at the sixth intercostal space in the median axillary line. A single
      flexible port was used. Both the camera and the endoinstruments were introduced
      through the port. Patient characteristics, visual analog score, and postoperative
      paresthesia scores were evaluated. RESULTS: The study enrolled 38 women and 60
      men with the mean age of 49.1+/-1.5 years (range, 19 to 75 y). Thirty-one
      patients (28.6%) were diagnosed with malignant pleural effusion. Perioperative
      pleurodesis with talc was performed in 81% of them. One-port VATS approach was
      used for pleura biopsies in 77 (78.6%), wedge resection in 4 (3.8%), pleurectomy
      in 13 (12.4%), and biopsy with talc chemical pleurodesis in 4 (3.8%) instances.
      The mean operation time was 24.4 minutes (range, 15 to 50 min). No major
      cardiorespiratory or surgical complications were noted. The median observation
      time was 60 months (range, 36+/-81 mo). Among benign pathology patients, 56
      (82.3%) of them did not complain about any pain; however, 12 patients had
      prolonged discomfort (2 pinprick, 6 numbness, and 4 pruritus). CONCLUSIONS: One
      port VATS in selected patients are feasible and seems to be safe in thoracic
      surgical interventions instead of conventional 3 ports that was presented in this
      series.

PMID- 24732736
TI  - Totally laparoscopic caudate lobe resection: technical aspects and literature
      review.
AB  - The particular anatomic location of the hepatic caudate lobe between the hilar
      plate and inferior vena cava means that it is still considered unsuitable for
      laparoscopic measures and a difficult site even for conventional surgery. Here we
      describe the first case to be reported in the literature of caudate lobe
      resection for a single metastasis from breast adenocarcinoma that was completed
      using an exclusively laparoscopic procedure and a simplified scheme involving the
      placement of 4 trocars, without any need for conversion or the Pringle maneuver.
      The patient was 31 years old with a history of radical right mastectomy and
      chemotherapy. The patient's postoperative course was uneventful and she was
      discharged 4 days after the surgery. Twelve months on, she is currently alive and
      disease free. 

PMID- 24732737
TI  - Minimally invasive 3-field esophagectomy with cervical single-port access.
AB  - BACKGROUND: Minimally invasive esophagectomy for esophageal cancer include
      thoracoscopic and laparoscopic esophagectomy with a cervical single-port assist,
      which is inadequate for both techniques. This is the first reported series
      applying this technique to treat esophageal cancer patients in literature.
      MATERIALS AND METHODS: From March 2007 to April 2011, 12 cases of laparoscopic
      and thoracoscopic total esophagectomy with a cervical single-port assist were
      performed. Indications for minimally invasive esophagectomy included esophageal
      squamous cell carcinoma, diagnosed preoperatively in nonmetastatic tumors and
      fewer than 4 lymph nodes by endoscopic ultrasonography. RESULTS: The mean
      operative time was 440 minutes (range, 347 to 578 min). The mean intensive care
      stay was 1.6 days (range, 0 to 6 d). The mean hospital stay was 11.8 days (range,
      7 to 22 d). Minor complications included atrial fibrillation (n=1), pleural
      effusion (n=2), and persistent air leaks (n=1), and major complications included
      cervical anastomotic leak in 1 patient due to technical failure. The 30-day
      mortality rate was 0. CONCLUSIONS: Video-assisted thoracoscopic and laparoscopic
      esophagectomy combined with a cervical single-port assist is a safe and minimally
      invasive technique for whole esophagus and mediastinal lymph node dissection.
      This technique allows for the clear visualization of the mediastinum, reducing
      the risk of surgery-related trauma.

PMID- 24732738
TI  - Comparison of video-assisted thoracoscopic surgery and median sternotomy
      approaches for thymic tumor resections at a single institution.
AB  - PURPOSE: This study was designed to evaluate the feasibility and safety of video
      assisted thoracoscopic surgery (VATS), and to compare the surgical results of
      VATS with the standard median sternotomy (MS) approach. MATERIALS AND METHODS:
      Between April 2010 and April 2012, the data of 245 patients who underwent
      thymectomy for thymic tumors were prospectively collected. Among them, 93
      patients with clinical stage I-II disease were retrospectively reviewed. RESULTS:
      Resection was planned for VATS in 49 cases, and for MS in 44 cases. During
      operation, there were 3 conversions to open surgery because of local invasion
      (conversion to thoracotomy in 1 patient, and sternotomy in 2). No transfusion was
      required in any patient. There was no significant difference in duration or
      amount of postoperative chest tube drainage between the 2 groups (P>0.05).
      Operative time, blood loss during operation, average length of the intensive care
      unit stay, and length of hospital stay were significantly less in the VATS group
      than the MS group (P<0.05). There were no major perioperative complications or
      mortality. No recurrence was detected during a median follow-up of 27 months
      (range, 12 to 36 mo). CONCLUSIONS: VATS thymectomy for early-stage thymic tumors
      is safe and feasible. In comparison with standard MS, the VATS approach was
      associated with a shorter intensive care unit stay and hospital stay. Prospective
      randomized multi-institutional trials with long-term follow-up are needed to
      compare the oncological outcomes.

PMID- 24732739
TI  - Ligasure versus stapled hemorrhoidectomy in the treatment of hemorrhoids: a meta
      analysis of randomized control trials.
AB  - The aim of this meta-analysis was to compare the outcomes of Ligasure
      hemorrhoidectomy and stapled hemorrhoidectomy for prolapsed hemorrhoids. Original
      studies in any language were searched from MEDLINE database, PubMed, Web of
      science and the Cochrane Library database, and Wangfang database. Randomized
      control trials that compared Ligasure hemorrhoidectomy with stapled
      hemorrhoidectomy were identified. Data were extracted independently for each
      study, and a meta-analysis was performed using fixed and random-effects models.
      Five trials including 397 patients met the inclusion criteria. Patients treated
      with Ligasure had a significantly shorter operative time compared with patients
      who underwent stapler techniques. The recurrence rate was higher in patients who
      underwent stapled hemorrhoidectomy. No statistically significant differences were
      observed in postoperative bleeding, urinary retention, difficult defecating, anal
      fissure, anal stenosis, incontinence, postoperative pain, return to normal
      activities, and hospital stay. Our meta-analysis shows that Ligasure is an
      effective instrument for hemorrhoidectomy, which results in shorter operation
      time and lower recurrence rate. 

PMID- 24732740
TI  - Long-term oncologic outcomes of laparoscopic right hemicolectomy during the
      learning curve period: comparative study with cases after the learning curve
      period.
AB  - BACKGROUND: This study aimed to assess the learning curve in laparoscopic right
      hemicolectomy and compare the long-term oncologic outcomes of the learning curve
      period. MATERIALS AND METHODS: We retrospectively reviewed 97 patients who
      underwent a laparoscopic right hemicolectomy by a single surgeon between July
      2006 and January 2009. Among them, 87 patients, excluding patients with stage IV
      (n=10) disease, were evaluated for long-term oncologic outcomes. They were
      divided into 2 phases: phase 1 (the learning curve period) and phase 2 (the
      expert period). The cumulative sum method was used for estimating the learning
      curve. RESULTS: The learning curve was determined at the 42nd case. Patient
      characteristics and postoperative clinicopathologic outcomes were similar in both
      groups except for the operation time (212.5+/-65.0 min vs. 146.4+/-37.1 min;
      P<0.001) and length of stay (10.7+/-5.4 d vs. 8.4+/-2.9 d; P=0.015). The 5-year
      overall survival rates were similar in both groups throughout all stages. The 5
      year disease-free survival rate of stage III disease in phase 2 (85%) was better
      than that of phase 1 (53.3%; P=0.046). CONCLUSIONS: Laparoscopic right
      hemicolectomy during the learning curve period showed acceptable
      clinicopathologic outcomes. However, the 5-year disease-free survival rate was
      compromised in patients with stage III disease in phase I.

PMID- 24732741
TI  - Transition towards laparoscopic appendicectomy at a UK center over a 7-year
      period.
AB  - BACKGROUND: Acute appendicitis remains the most common indication for emergency
      abdominal surgery in the United Kingdom. Although laparoscopic appendicectomy has
      demonstrable advantages over open appendicectomy, uptake has not been universal.
      The aims of this study were to describe trends in laparoscopic appendicectomy in
      a District General Hospital in Scotland. METHODS: Retrospective review of
      appendix histopathology records within NHS Fife between 2003 and 2010. Note
      review of cases of acute appendicitis managed with laparoscopic appendicectomy
      was performed. Perioperative variables in perforated and nonperforated
      appendicitis were compared. A multivariate logistic regression analysis to
      determine factors associated with developing complications was performed.
      RESULTS: Between 2003 and 2010, 237 laparoscopic appendicectomies were performed.
      The rate of laparoscopic appendicectomy increased from 2.5% in 2003 to 78% in
      2010. In 50% of cases, the trainee surgeon was the primary operator.
      Complications occurred in 9.6% and the mortality rate was 0.4%. No factors on
      multivariate logistic regression predicted development of complications.
      CONCLUSIONS: We describe a change in practice towards laparoscopic appendicectomy
      for the treatment of acute appendicitis over a 7-year period. Furthermore,
      laparoscopic appendicectomy is associated with acceptable morbidity rates.

PMID- 24732742
TI  - A case series of adult intussusception managed laparoscopically.
AB  - OBJECTIVE: Adult intussusception is rare, representing only 1% to 5% of bowel
      obstructions. This is a case series of 8 patients who presented with intestinal
      obstruction secondary to intussusception managed laparoscopically at our
      institution. METHODS: Eight cases of adult intussusceptions were treated
      laparoscopically at our institution between January 2010 and December 2012. The
      presentation, diagnosis, management strategy, and pathology involved were
      reviewed. RESULTS: Three patients presented with small-bowel obstruction, whereas
      4 had recurrent bouts of abdominal pain and 1 had persisting diarrhea. Computed
      tomography scan was performed in all but 1 of our patients and was accurate in
      diagnosing in all instances. Laparoscopy and resection of the intussusceptions
      was completed successfully in all patients. There were no intraoperative and
      postoperative complications. Four patients underwent laparoscopy-assisted small
      bowel resection; 3 patients underwent right hemicolectomy and 1 had anterior
      resection. All patients recovered uneventfully. CONCLUSIONS: Laparoscopic
      management of adult intussusception is safe and feasible. Further, diagnostic
      laparoscopy is useful when the diagnosis is uncertain despite computed tomography
      scan imaging.

PMID- 24732743
TI  - The usefulness and safety of the introducer technique using a bumper-button-type
      device as compared with the pull method for percutaneous endoscopic gastrostomy.
AB  - PURPOSE: To describe our initial experiences with the standardized introducer
      technique for percutaneous endoscopic gastrostomy and to compare clinical
      outcomes and complications with the pull technique. METHODS: The introducer
      technique was used on 91 patients. The clinical outcomes of procedures were
      retrospectively collected and compared with those of 22 patients who had
      procedures using the pull technique. RESULTS: Mean operation time was
      significantly longer in the introducer technique group as compared with the pull
      technique group. Increased inflammation markers (body temperature, white blood
      cell count, and C-reactive protein) were observed in the pull technique group as
      compared with the introducer technique group. Incidences of peristomal infection
      and pneumonia were lower in the introducer method group than in the pull method
      group. CONCLUSIONS: The introducer technique is a useful and safe method for
      percutaneous endoscopic gastrostomy in terms of reduced incidences of peristomal
      infection, pneumonia, pain, and discomfort.

PMID- 24732744
TI  - Laparoscopic common bile duct exploration in cirrhotic patients with
      choledocholithiasis.
AB  - BACKGROUND: Although laparoscopic common bile duct exploration (LCBDE) has become
      the standard procedure for most choledocholithiasis patients, the application of
      this procedure to liver cirrhosis is still in debate. The aim of current study
      was to evaluate the feasibility and safety of LCBDE in choledocholithiasis
      patients with compensated liver cirrhosis. MATERIALS AND METHODS: From January
      2006 to December 2012, 346 LCBDE performed in our hospital. According to previous
      defined liver condition, the patients were divided into group A (liver cirrhosis,
      n=132) and group B (without cirrhosis, n=214). The perioperative data for the 2
      groups were retrospectively reviewed and compared. RESULTS: LCBDE was
      successfully completed in 326 patients. Conversion from laparoscopic to open
      surgery was necessary for 20 patients (5.7%) mainly because of hemorrhage (5,
      25%) and severe adhesions (8, 40%); a T-tube was placed in 211 patients (64.7%),
      and primary closure was done in 115 (35.3%). There was significant difference for
      groups A and B in term of intraoperative blood loss (85 vs. 35 mL; P<0.01).
      However, the 2 groups showed no significant differences with respect to mean
      operation time (2.1 vs. 1.9 h; P=0.07), complication rates (10.6% vs. 8.8%;
      P=0.6), and mean hospital stay (4.2 vs. 4.0 d; P=0.6), conversion rate (5.3% vs.
      6.1%; P=0.77), and retained choledocholithiasis rate (8.3% vs. 7.1%; P=0.65).
      There was no mortality in both the groups. CONCLUSION: LCBDE is a feasible,
      effective, and safe surgical procedure for choledocholithiasis patients with
      compensated cirrhosis.

PMID- 24732745
TI  - Laparoscopic anterior approach of major hepatectomy combined with colorectal
      resection for synchronous colorectal liver metastases.
AB  - PURPOSE: The aim of the study was to evaluate the feasibility and operative
      outcomes of the anterior approach technique for a simultaneous colorectal and
      liver laparoscopic procedure given its demonstrated benefits and discuss the
      advantages of this strategy. PATIENT AND METHODS: In the presented case, a total
      laparoscopic anterior approach was used for a left hemihepatectomy in combination
      with laparoscopic colorectal resections for synchronous liver metastases, which
      emphasizes the technical aspects of this procedure. The duration of surgery,
      blood loss, and postoperative outcomes were evaluated. RESULTS: The laparoscopic
      anterior approach for a left hepatectomy with simultaneous colon resection for
      liver metastases was feasible and safe without postoperative complications. The
      duration of surgery was 190 minutes with an estimated blood loss of 200 mL. The
      postoperative course was uneventful. CONCLUSIONS: The laparoscopic anterior
      approach for a major hepatectomy for unilobular synchronous metastases can be
      safely performed simultaneously with colorectal surgery in select patients.

PMID- 24732746
TI  - Clinical outcome of single plastic stent treatment of benign iatrogenic biliary
      strictures: is the outcome predetermined?
AB  - Endoscopic retrograde cholangiopancreatography (ERCP) is used for the management
      of benign iatrogenic biliary strictures after cholecystectomy and liver
      transplantation. Multiple stents can injure biliary circulation. If resolution of
      reversible ductal edema and/or ischemia is the mechanism for successful therapy
      then single stent placement for benign biliary stricture should work.
      Retrospectively reviewed ERCP records between November 1999 and 2012 provided 25
      patients with repeat ERCPs performed at 10-week intervals or if symptoms of stent
      occlusion were present. If strictures did not improve between stent changes and
      if removal was not an option, hepaticojejunostomy was used. Strictures resolved
      in 72% of patients. Seven patients underwent hepaticojejunostomy. Three had ERCP
      related complications. No stricture recurrence occurred during the follow-up
      period. Endoscopic single plastic stent treatment of benign biliary iatrogenic
      strictures has comparable success to multiple stenting. Many postsurgical
      strictures may have reversible ischemic/edematous component with stenting to
      maintain bile drainage. 

PMID- 24732747
TI  - The influence on immunologic parameters during NOTES in a porcine survival model.
AB  - OBJECTIVE: To analyze the effect of natural orifice transluminal endoscopic
      surgery (NOTES) on the survival of animals, by comparing the change of
      intraoperative and postoperative immunologic parameters of NOTES with
      laparoscopy. MATERIALS AND METHODS: Twenty pigs were randomized to treatment with
      NOTES or standard laparoscopy. Each group underwent diagnostic peritoneoscopy by
      laparoscopy or NOTES in 90 minutes. Laboratory values, including interleukin-1
      (IL-1) and tumor necrosis factor-alpha (TNF-alpha), were obtained at baseline, at
      intraoperative minute (IOM) 30, 60, and 90, and on postoperative day (POD) 1, 3,
      and 7. RESULTS: All procedures were successfully completed and all animals
      (except one in the NOTES group) survived to POD 14. The level of IL-1 and TNF
      alpha was not significantly different compared with the preoperative level of IL
      1 and TNF-alpha in both groups at IOM 30 and 60. It increased significantly at
      IOM 90 and POD 1 and 3 in both groups. Although levels of both IL-1 and TNF-alpha
      were higher in the NOTES group compared with the other group, there was no
      significant difference between the groups. At POD 7, the level of IL-1 and TNF
      alpha decreased to near-normal levels in both groups. CONCLUSIONS: Although
      preliminary, the findings in this study do not currently support the assumption
      that NOTES is less invasive than laparoscopy. Further research is required to
      confirm these findings.

PMID- 24732748
TI  - Review of psychodynamic psychotherapy neuroimaging studies.
AB  - The clinical efficacy of psychodynamic psychotherapy (PDT) has undergone
      extensive study and review. Recently, researchers have studied the effects of
      this treatment on brain metabolic or synaptic activity, but the collective
      findings have never been reviewed. The objective of this review was to describe
      the findings of all neuroimaging studies of any form of PDT treatment. An
      extensive literature search through databases along with surveying of research
      groups were undertaken to acquire all available published studies. Eleven series
      were included in the final sample, consisting of 2 randomized controlled trials,
      5 controlled trials and 4 case series, altogether involving 210 people: 94
      healthy controls and 116 people with mood disorders, panic disorder, somatoform
      disorders and borderline personality disorder. A variety of neuroimaging
      techniques were used to examine regional metabolic activity and synaptic
      neurotransmission before and after treatment. The common finding was
      normalization of synaptic or metabolic activity in limbic, midbrain and
      prefrontal regions, occurring in association with improved clinical outcomes. PDT
      has demonstrable effects on brain function in diverse clinical populations as
      evidenced by a modest group of mixed neuroimaging studies.

PMID- 24732749
TI  - Spontaneous emergence of large-scale cell cycle synchronization in amoeba
      colonies.
AB  - Unicellular eukaryotic amoebae Dictyostelium discoideum are generally believed to
      grow in their vegetative state as single cells until starvation, when their
      collective aspect emerges and they differentiate to form a multicellular slime
      mold. While major efforts continue to be aimed at their starvation-induced social
      aspect, our understanding of population dynamics and cell cycle in the vegetative
      growth phase has remained incomplete. Here we show that cell populations grown on
      a substrate spontaneously synchronize their cell cycles within several hours.
      These collective population-wide cell cycle oscillations span millimeter length
      scales and can be completely suppressed by washing away putative cell-secreted
      signals, implying signaling by means of a diffusible growth factor or mitogen.
      These observations give strong evidence for collective proliferation behavior in
      the vegetative state. 

PMID- 24732750
TI  - Management of bleeding gastric varices: a single session of histoacryl injection
      may be sufficient.
AB  - OBJECTIVE: Gastric variceal bleeding is one of the most feared complications of
      portal hypertension and hence merits investigation for its optimal therapy. We
      aimed to evaluate the efficacy and long-term outcome(s) of patients treated with
      a single session of histoacryl sclerotherapy for active gastric variceal
      bleeding. METHODS: The medical records of patients who presented with active
      gastric variceal bleeding between 1998 and 2011 in a tertiary care setting were
      evaluated retrospectively and the eventual outcome(s) (initial hemostasis,
      rebleeding, and mortality rate) was assessed at least 1 year after the index
      bleed. RESULTS: Ninety-seven patients were included. The mean age of the patients
      was 51.0 +/- 12.5 years; 62% were men. Hepatitis C was the most common etiology,
      found in 63 (65%) patients. The majority of the patients were classified as Child
      Pugh grade B and C: 44 (46%) and 29 (31%) patients, respectively. A total of 40
      (41%) patients were IGV1, 35 (36%) patients were GOV 2, 20 (21%) patients were
      GOV 1, and 2 (2%) patients were IGV2. A single session of histoacryl was
      successful in controlling bleeding in 83 (86%) patients. Seven (7%) patients died
      during the hospital stay. Rebleeding was observed in 24 (27%) patients during the
      1-year follow-up, of whom 12 (50%) were managed successfully with repeated
      histoacryl injection. The overall mortality rate at 6 weeks, 6 months, and 1 year
      was 14 (14%), 19 (20%) and 26 (27%) patients, respectively. Child-Pugh
      classification was a significant prognostic factor of survival (P<0.001).
      CONCLUSION: A single session of histoacryl sclerotherapy is effective in the
      majority of patients with active gastric variceal bleeding. Rebleeding was
      observed in one-fourth of patients, half of whom were controlled successfully by
      repeated histoacryl sclerotherapy.

PMID- 24732751
TI  - Correlation of clinical, endoscopic, and histological findings with virulence
      factors in children with Helicobacter pylori gastritis.
AB  - BACKGROUND AND GOALS: As there are limited data regarding the correlation between
      virulence factors and clinical, endoscopic, and histological findings in children
      with Helicobacter pylori gastritis, we aimed to evaluate that probable
      relationship in pediatric cases. STUDY: One hundred and fifty-nine children with
      chronic abdominal pain or dyspepsia were included in this study. Upper
      gastrointestinal endoscopy was performed and multiple biopsy samples were taken
      from the esophagus, the antrum, and the duodenum. PCR was used for the
      determination of virulence factors. RESULTS: According to PCR analysis, 98
      (61.6%) children were positive for H. pylori. Using histopathological examination
      and culture, H. pylori was detected in 65 (40.9%) and 51 (32.1%) children,
      respectively. Peptic ulcer prevalence and histopathological features were not
      different among cagA, cagE, or iceA1 positive and negative groups (P>0.05).
      Peptic ulcer prevalence and histopathological findings were more common in iceA2
      positive patients (P<0.05). Antral nodularity was more common in cagA-positive
      patients (P<0.05). Endoscopic and histological features were not different among
      patients with or without m1 or m2 strains (P>0.05). S1b positivity was associated
      with a higher esophagitis rate (P<0.05). CONCLUSION: Among virulence factors,
      iceA2 was associated with peptic ulcer and milder histopathological findings, and
      vacAs1 was associated with milder histopathological findings.

PMID- 24732752
TI  - Effect of fluvastatin on 24-week telaprevir-based combination therapy for
      hepatitis C virus genotype 1b-infected chronic hepatitis C.
AB  - OBJECTIVES: The addition of fluvastatin significantly improves sustained
      virological response (SVR) in pegylated interferon and ribavirin (peg-IFN/RBV)
      combination therapy for patients infected with the hepatitis C virus. However,
      the add-on effect on telaprevir-based triple combination therapy remains unknown.
      The aim of this study was to investigate the effect of fluvastatin on telaprevir
      based combination therapy by conducting a prospective, open-label, randomized,
      controlled trial. PATIENTS AND METHODS: Among 124 genotype 1b-infected chronic
      hepatitis C patients recruited, 116 eligible patients were allocated randomly to
      two study arms; they received 12 weeks of telaprevir/peg-IFN/RBV, followed by 12
      weeks of peg-IFN/RBV with or without 24 weeks of fluvastatin (fluvastatin group
      and control group, respectively). Treatment outcomes and adverse effects were
      compared between the two groups. RESULTS: There were 56 men and 60 women, median
      age 60 years (range, 28-71 years). Rapid virological response and end of
      treatment response rates were 87.9% (51/58) and 96.6% (56/58) in the control
      group and 75.9% (44/58) and 98.3% (57/58) in the fluvastatin group, respectively.
      SVR rates in the control group and the fluvastatin group were 84.5% (49/58) and
      81.0% (47/58), respectively; there was no significant difference (P=0.806).
      Stratified analysis showed that no factors associated with the SVR rate were
      found between the two groups. No adverse events were associated with fluvastatin.
      CONCLUSION: In this trial, administration of fluvastatin with telaprevir/peg
      IFN/RBV was a safe combination. However, fluvastatin had no add-on effect on 24
      week telaprevir-based combination therapy for chronic hepatitis C genotype 1b
      infected patients.

PMID- 24732753
TI  - Integration of thermodynamic, quantum and hierarchical theories of information in
      the context of Peircean semiosis--a review.
AB  - I claim that Peirce's notion of information and sign iteration as an
      intermediation between potentialities that are actualized and actualities that
      are potentiated provides a suitable framework for interpretation of Zurek'
      Information gathering and using systems (IGUS). Moreover, this model can be
      extended to address the problem of quantum measurement (QM) since it allows
      exploring an alternative view based on IGUS understood as agents of internal
      measurement, beyond Copenhagen interpretation (CI) that invokes a classical
      observer that performs measurements and the "many worlds interpretation" (MWI)
      that rejects all sort of observers and measurements. This integrative view allows
      figuring out a hierarchy of IGUS-like systems of interpretation that explore new
      possibilities in the upper level analog boundary and consolidate actualized
      information in the lower level digital boundary. 

PMID- 24732755
TI  - Minimally invasive percutaneous nephrolithotomy in children less than three years
      of age: five-year experience in 234 cases.
AB  - OBJECTIVE: The treatment of infant renal stones is still a huge challenge to the
      urologist. The present study aimed to evaluate the safety and efficiency of the
      minimally invasive percutaneous nephrolithotomy (MPCNL) method as a treatment for
      infant renal stones, and also to analyze the specific techniques and related
      complications of the procedure. PATIENTS AND METHODS: From January 2008 to
      December 2012, 234 cases (72 girls and 162 boys, mean age 15.8 months, range 5-36
      months) aged under 3 years and treated with MPCNL for renal stones were analyzed
      retrospectively. 125 cases were younger than 12 months, 67 cases were between 13
      and 24 months and 42 cases between 25 and 36 months. The indications for MPCNL
      were (1) stone over 1 cm(2), (2) hydronephrosis and (3) recurrent urinary tract
      infection. An initial percutaneous access to the targeted renal calyx was
      obtained through an ultrasound-guided peripheral calyceal puncture. Stones were
      fragmented by a holmium laser with a pediatric nephroscope via 14-F tract.
      RESULTS: All the procedures were performed by single tract, and totally 247
      tracts were established, including 245 14-F tracts, 1 16-F tract and 1 12-F
      tract, respectively. The stones were located in the left kidney (n = 91), right
      kidney (n = 105) and in both kidneys (n = 28), respectively. Regarding the
      puncture point, in 228 cases it was in the 12th subcostal space and in 19 cases
      in the 11th intercostal space. The distribution of target puncture calyx and the
      subsequent residual calculi were as follows: 39 cases in the upper calyx with 2
      cases of stone residual, 148 in the middle calyx with 3 stone residuals, and 60
      in the lower calyx with 2 stone residuals, respectively. As a result, completely
      stone-free state was achieved in 240 kidney units (97.2%). The mean operating
      time was 32.5 min. None of the patients required blood transfusion and no septic
      shock occurred after operation. A large quantity of washing fluid was infiltrated
      into the abdominal cavity in 3 cases. CONCLUSION: Using a single tract <=14 F,
      MPCNL is a safe and effective procedure in the management of renal stones in
      infant less than 3 years old.

PMID- 24732754
TI  - HIV-associated neuropathogenesis: a systems biology perspective for modeling and
      therapy.
AB  - Despite the development of powerful antiretroviral drugs, HIV-1 associated
      neurological disorders (HAND) will affect approximately half of those infected
      with HIV-1. Combined anti-retroviral therapy (cART) targets viral replication and
      increases T-cell counts, but it does not always control macrophage polarization,
      brain infection or inflammation. Moreover, it remains difficult to identify those
      at risk for HAND. New therapies that focus on modulating host immune response by
      making use of biological pathways could prove to be more effective than cART for
      the treatment of neuroAIDS. Additionally, while numerous HAND biomarkers have
      been suggested, they are of little use without methods for appropriate data
      integration and a systems-level interpretation. Machine learning, could be used
      to develop multifactorial computational models that provide clinicians and
      researchers with the ability to identify which factors (in what combination and
      relative importance) are considered important to outcome. 

PMID- 24732756
TI  - Selected ABCB1, ABCB4 and ABCC2 polymorphisms do not enhance the risk of drug
      induced hepatotoxicity in a Spanish cohort.
AB  - BACKGROUND AND AIMS: Flawed ABC transporter functions may contribute to increased
      risk of drug-induced liver injury (DILI). We aimed to analyse the influence of
      genetic variations in ABC transporters on the risk of DILI development and
      clinical presentations in a large Spanish DILI cohort. METHODS: A total of ten
      polymorphisms in ABCB1 (1236T>C, 2677G>T,A, 3435T>C), ABCB4 (1954A>G) and ABCC2 (
      1774G>del, -1549A>G, -24C>T, 1249G>A, 3972C>T and 4544G>A) were genotyped using
      Taqman 5' allelic discrimination assays or sequencing in 141 Spanish DILI
      patients and 161 controls. The influence of specific genotypes, alleles and
      haplotypes on the risk of DILI development and clinical presentations was
      analysed. RESULTS: None of the individual polymorphisms or haplotypes was found
      to be associated with DILI development. Carriers homozygous for the ABCC2 
      1774del allele were however only found in DILI patients. Hence, this genotype
      could potentially be associated with increased risk, though its low frequency in
      our Spanish cohort prevented a final conclusion. Furthermore, carriers homozygous
      for the ABCC2 -1774G/-1549A/-24T/1249G/3972T/4544G haplotype were found to have a
      higher propensity for total bilirubin elevations when developing DILI.
      CONCLUSIONS: Our findings do not support a role for the analysed polymorphisms in
      the ABCB1, ABCB4 and ABCC2 transporter genes in DILI development in Spanish
      patients. The ABCC2 -1774deldel genotype was however restricted to DILI cases and
      could potentially contribute to enhanced DILI susceptibility.

PMID- 24732757
TI  - Effective dystrophin restoration by a novel muscle-homing peptide-morpholino
      conjugate in dystrophin-deficient mdx mice.
AB  - Antisense oligonucleotide (AO)-mediated splice correction therapy for Duchenne
      muscular dystrophy has shown huge promise from recent phase 2b clinical trials,
      however high doses and costs are required and targeted delivery can lower both of
      these. We have previously demonstrated the feasibility of targeted delivery of
      AOs by conjugating a chimeric peptide, consisting of a muscle-specific peptide
      and a cell-penetrating peptide, to AOs in mdx mice. Although increased uptake in
      muscle was observed, the majority of peptide-AO conjugate was found in the liver.
      To search for more effective muscle-homing peptides, we carried out in vitro
      biopanning in myoblasts and identified a novel 12-mer peptide (M12) showing
      preferential binding to skeletal muscle compared to the liver. When conjugated to
      phosphorodiamidate morpholino oligomers, ~25% of normal level of dystrophin
      expression was achieved in body-wide skeletal muscles in mdx mice with
      significant recovery in grip strength, whereas <2% in corresponding tissues
      treated with either muscle-specific peptide-phosphorodiamidate morpholino
      oligomer or unmodified phosphorodiamidate morpholino oligomer under identical
      conditions. Our data provide evidences for the first time that a muscle-homing
      peptide alone can enhance AO delivery to muscle without appreciable toxicity at
      75 mg/kg, suggesting M12-phosphorodiamidate morpholino oligomer can be an
      alternative option to current AOs. 

PMID- 24732758
TI  - Age-related macular degeneration: clinical findings, histopathology and imaging
      techniques.
AB  - Age-related macular degeneration (AMD) is the most common cause of blindness
      among people over age 55 years in industrialized countries. Known major risk
      factors for AMD include: age >55 years, history of smoking, white race, and
      mutations in various components of the complement system. Early AMD is
      characterized by the presence of drusen and pigmentary abnormalities. Late AMD is
      associated with central visual loss and is characterized by the presence of
      choroidal neovascularization and/or geographic atrophy. Early AMD is associated
      with a number of biochemical abnormalities including oxidative damage to retinal
      pigment epithelium (RPE) cells, complement deposition in the RPE-Bruch's membrane
      choriocapillaris complex, lipidization of Bruch's membrane, and extracellular
      matrix abnormalities (e.g. collagen crosslinking, advanced glycation end product
      formation). Antiangiogenic drugs block the vascular leakage associated with
      choroidal new vessels, thus reducing retinal edema and stabilizing or restoring
      vision. At this time, there are no proven effective treatments for the
      nonexudative complications of AMD. Modern ocular imaging technologies (including
      spectral domain and phase variance optical coherence tomography, short- and long
      wavelength fundus autofluorescence, adaptive optics-scanning laser
      ophthalmoscopy, and near-infrared reflectance) enable one to follow changes in
      the RPE, photoreceptors, and choriocapillaris quantitatively as the disease
      progresses. In addition, one can quantitatively assess the volume of drusen and
      areas of atrophy. These data, when correlated with the known histopathology of
      AMD, may provide useful measures of treatment efficacy that are likely to be more
      sensitive and reproducible than conventional end points such as visual acuity and
      rate of enlargement of geographic atrophy. As a result, these imaging
      technologies may be valuable in assessing the effects of cell-based therapy for
      patients with AMD.

PMID- 24732759
TI  - General pathophysiology in retinal degeneration.
AB  - Retinal degeneration, including that seen in age-related macular degeneration and
      retinitis pigmentosa (RP), is the most common form of neural degenerative disease
      in the world. There is great genetic and allelic heterogeneity of the various
      retinal dystrophies. Classifications of these diseases can be ambiguous, as there
      are similar clinical presentations in retinal degenerations arising from
      different genetic mechanisms. As would be expected, alterations in the activity
      of the phototransduction cascade, such as changes affecting the renewal and
      shedding of the photoreceptor OS, visual transduction, and/or retinol metabolism
      have a great impact on the health of the retina. Mutations within any of the
      molecules responsible for these visual processes cause several types of retinal
      and retinal pigment epithelium degenerative diseases. Apoptosis has been
      implicated in the rod cell loss seen in a mouse model of RP, but the precise
      mechanisms that connect the activation of these pathways to the loss of
      phosphodiesterase (PDE6beta) function has yet to be defined. Additionally, the
      activation of apoptosis by CCAAT/-enhancer-binding protein homologous protein
      (CHOP), after activation of the unfolded protein response pathway, may be
      responsible for cell death, although the mechanism remains unknown. However, the
      mechanisms of cell death after loss of function of PDE6, which is a commonly
      studied mammalian model in research, may be generalizable to loss of function of
      different key proteins involved in the phototransduction cascade.

PMID- 24732760
TI  - Juvenile-onset macular degeneration and allied disorders.
AB  - While age-related macular degeneration (AMD) is a leading cause of central vision
      loss among the elderly, many inherited diseases that present earlier in life
      share features of AMD. These diseases of juvenile-onset macular degeneration
      include Stargardt disease, Best disease, retinitis pigmentosa, X-linked
      retinoschisis, and other allied disorders. In particular, they can be accompanied
      by the appearance of drusen, geographic atrophy, macular hyperpigmentation,
      choroidal neovascularization, and disciform scarring just as in AMD, and often
      may be confused for the adult form of the disease. Diagnosis based on funduscopic
      findings alone can be challenging. However, the use of diagnostic studies such as
      electroretinography, electrooculography, optical coherence tomography, and fundus
      autofluorescence in conjunction with genetic testing can lead to an accurate
      diagnosis.

PMID- 24732761
TI  - Diagnosis and complementary examinations.
AB  - Development of neuroprotective therapies requires an understanding of the
      mechanisms of retinal degeneration and a way to monitor response to treatment.
      With the increasing availability of genetic testing, precise characterization of
      the retinal degeneration phenotype is essential. This chapter covers standard and
      innovative diagnostic techniques and complementary examinations needed for the
      evaluation and treatment of retinal degenerative diseases. It aims to provide an
      overview of functional and structural diagnostic tools for the evaluation of
      retinal degenerative diseases, but is not intended as a comprehensive reference.
      Subjective assessment of visual function includes psychophysical tests, such as
      perimetry and microperimetry. Electrophysiology tests, such as the
      electroretinogram and electro-oculogram, are crucial in the assessment of retinal
      degenerative diseases and provide an objective assessment of global photoreceptor
      and retinal pigment epithelial cell function. Retinal structural measures are
      correlated with measures of retinal function to characterize the disease
      phenotype, including fundus photography using color, near-infrared, and
      autofluorescence imaging. Ocular perfusion can be assessed using fluorescein,
      indocyanine green, and noninvasive angiography. Optical coherence tomography
      provides information about retinal structure. Resolution of all images of retinal
      structure can be improved using adaptive optics, which permits visualization of
      individual photoreceptors and retinal pigment epithelial cells in the macula.

PMID- 24732762
TI  - Stem cells for retinal repair.
AB  - Remarkable progress over the past decade has led to the first clinical studies of
      stem cell therapy for retinal disease. The unique access retina offers for
      implantation, monitoring, and ablation is well suited for stem cell trials, and
      retinal applications have now moved to the forefront of the field of regenerative
      medicine. Retinal progeny derived from either pluripotent stem cells or tissue
      specific retinal and retinal pigment epithelium (RPE) stem cells have the
      capacity both to replace damaged retina and to provide trophic support that slows
      disease progression. In contrast, bone marrow and neural stem cells produce
      nonretinal progeny that provide trophic support but with limited integration and
      capacity to differentiate into retinal progeny that can replace damaged retinal
      tissue. Embryonic and induced pluripotent stem cells differentiated into neural
      retinal and RPE progeny provide an unlimited supply of human cells for
      transplantation and disease modeling but raise the risks of aberrant
      differentiation and over proliferation. Tissue-specific stem cells isolated from
      neural retina or RPE that are naturally committed to retinal fates have a
      restricted lineage potential that improves the margin of safety. This improved
      safety of retina and RPE stem cells is balanced, however, by a restricted
      proliferative potential, which limits the quantity of progeny produced. In this
      chapter, we review the types of stem cells under development for retinal therapy.

PMID- 24732763
TI  - Differentiation of pluripotent stem cells into retinal pigmented epithelium.
AB  - Ocular diseases affect millions worldwide and dramatically influence the quality
      of life. Although much is known about ocular biology and disease pathologies,
      effective treatments are still lacking. The eye is well suited for application of
      emerging cell-based therapies. This chapter explores the development of stem cell
      based treatments for age-related macular degeneration (AMD), a prevalent ocular
      disease in the elderly. Retinal pigmented epithelium (RPE), a cell type
      implicated in AMD, has been derived from both induced pluripotent stem cells and
      embryonic stem cells (ESC). Rapidly advancing research has generated various
      methods of RPE differentiation and several transplantation strategies. Clinical
      trials are already underway using suspensions of ESC-derived RPE and others are
      soon to follow. This chapter will provide an overview of current derivation and
      transplantation strategies for stem cell-derived RPE for the treatment of AMD and
      other related ocular diseases.

PMID- 24732764
TI  - Neural retinal regeneration with pluripotent stem cells.
AB  - Retinal degeneration represents a huge burden of blinding disease, and currently
      there are no effective treatments that reverse the most common causes of neural
      retinal degeneration. Stem cell biology has the potential to significantly ease
      this burden, not only through the development of disease models of retinal
      degeneration but also in the manufacture of a replacement for the neural retinal
      tissue. This review summarizes the major advancements in the last decade in the
      field of neural retinal regeneration with an emphasis on the differentiation of
      embryonic and induced pluripotent stem cells into cells with retinal and
      specifically photoreceptor characteristics.

PMID- 24732766
TI  - Stem cells: Immunology and immunomodulation.
AB  - Multipotent progenitor cells have the ability to differentiate in vitro into
      tissue-specific cells under the proper cellular signaling conditions. Because of
      this intrinsic property, pluripotent derived stem cells from embryonic tissues,
      induced from genetic reprogramming of somatic cells or from mesenchymal cells,
      have become the focus of many regenerative medicine studies directed toward
      application to clinical settings. Generation of retinal pigment epithelium
      derived from patient-specific, induced pluripotent stem cells may create the
      ability to recapitulate the disease state and screen new therapeutics, improving
      upon the limited treatment strategies currently available for afflicted patients.
      However, the method of delivery, cell culture differentiation, and immunological
      rejection are some of the limitations that continue to influence ongoing attempts
      for clinical applications. Understanding stem cell properties and the immune
      responses these cells elicit in vitro and in vivo will be of importance for
      designing successful protocols to overcome these immunological limitations. This
      chapter examines the immunological and immunomodulatory properties of multipotent
      stem cells in an attempt to provide insights for successful cellular
      transplantation.

PMID- 24732765
TI  - Stem cells, retinal ganglion cells and glaucoma.
AB  - Retinal ganglion cells (RGCs) represent an essential neuronal cell type for
      vision. These cells receive inputs from light-sensing photoreceptors via retinal
      interneurons and then relay these signals to the brain for further processing.
      RGC diseases that result in cell death, e.g. glaucoma, often lead to permanent
      damage since mammalian nerves do not regenerate. Stem cell differentiation can
      generate cells needed for replacement or can be used to generate cells capable of
      secreting protective factors to promote survival. In addition, stem cell-derived
      cells can be used in drug screening research. Here, we discuss the current state
      of stem cell research potential for interference in glaucoma and other optic
      nerve diseases with a focus on stem cell differentiation to RGCs.

PMID- 24732767
TI  - Biochemical restoration of aged human Bruch's membrane: experimental studies to
      improve retinal pigment epithelium transplant survival and differentiation.
AB  - Suspensions of human embryonic stem cell-derived retinal pigment epithelium (hES
      RPE) and human fetal RPE resurface aged and age-related macular degeneration
      (AMD) Bruch's membrane to a limited degree at day 21 in organ culture. Survival
      and differentiation of hES-RPE and human fetal RPE on aged or AMD Bruch's
      membrane are enhanced greatly (200%) if a biologically synthesized extracellular
      matrix (bovine corneal endothelial cell extracellular matrix) is laid down on
      Bruch's membrane prior to transplantation. Transplanted RPE survival is enhanced
      even more (400-1,000%) if Bruch's membrane is treated with bovine corneal
      endothelial cell-conditioned medium during organ culture of hES-RPE or fetal RPE
      on aged or AMD Bruch's membrane. Future efforts are focused on identifying the
      bioactive components of bovine corneal endothelial cell-conditioned medium, so
      that this material can be reconstituted for clinical use as an adjunct to improve
      RPE transplant survival and differentiation in AMD eyes.

PMID- 24732768
TI  - Approaches to cell delivery: substrates and scaffolds for cell therapy.
AB  - Retinal degeneration, associated with loss of photoreceptors, is the primary
      cause of permanent vision impairment, impacting millions of people worldwide. Age
      related macular degeneration and retinitis pigmentosa are two common retinal
      diseases resulting in photoreceptor loss and vision impairment or blindness.
      Presently, available treatments can only delay the progress of retinal
      degeneration, and there are no treatments that can restore permanent vision loss.
      Research is underway to develop methods of regenerating the impaired retina by
      delivering photoreceptor precursor cells and retinal pigment epithelium to the
      subretinal space. Challenges to cell transplantation include limited survival
      upon implantation and the formation of abnormal cell architectures in vivo.
      Retinal tissue engineering shows immense promise and potential in treatment of
      retinal degeneration by employing scaffold-based delivery systems of retinal
      progenitor cells to the subretinal space. Scaffold delivery strategy has been
      shown to enhance the cell survival and direct cell differentiation in a variety
      of retinal degenerative models. In this chapter, we summarize the research
      findings on different scaffold- or substrate-based transplantation techniques
      used to deliver retinal progenitor/photoreceptor precursors and retinal pigment
      epithelial cells to the subretinal space.

PMID- 24732769
TI  - Microdevice-based cell therapy for age-related macular degeneration.
AB  - This chapter reports the application of a micromachined parylene-C device as an
      artificial Bruch's membrane for the stem cell-based therapy of age-related
      macular degeneration. The feasibility of parylene-C as a substitute substrate
      material is demonstrated by evaluating the permeability of membranes of submicron
      thicknesses. It has been found that parylene-C membranes thinner than 0.3 um
      possess similar molecular weight exclusion limit and nutrient diffusion flux to
      that of the healthy human Bruch's membrane. This conclusion is further validated
      by the in vitro perfusion cell viability test. Since the submicron parylene-C
      itself is difficult to handle, we design a mesh-supported submicron parylene
      membrane (MSPM) to provide sufficient mechanical support. This MSPM can support
      the growth of retinal pigment epithelial (RPE) cells in a monolayer with well
      polarized morphology. Human embryonic stem cell-derived H9-RPE cells are cultured
      in vitro on the MSPM for one month before the implantation of the MSPM into the
      rat's retina. To facilitate the surgical implantation, a parylene-C/SU-8 hybrid
      microfluidic device is designed as an inserter. Histological studies with
      hematoxylin-eosin staining and immunofluorescence staining show that the
      implanted RPE cells adhere well to the artificial Bruch's membrane and are able
      to maintain high viability and normal morphology in vivo.

PMID- 24732770
TI  - Cell and gene therapy.
AB  - Replacement or repair of a dysfunctional gene combined with promoting cell
      survival is a two-pronged approach that addresses an unmet need in the therapy of
      retinal degenerative diseases. In this chapter, we discuss various strategies
      toward achieving both goals: transplantation of wild-type cells to replace
      degenerating cells and to rescue gene function, sequential gene and cell therapy,
      and in vivo reprogramming of rods to cones. These approaches highlight cutting
      edge advances in cell and gene therapy, and cellular lineage conversion in order
      to devise new therapies for various retinal degenerative diseases.

PMID- 24732771
TI  - Cellular manufacturing for clinical applications.
AB  - Rapid progress has been made in the development of novel cell-based approaches
      for the potential treatment of retinal degenerative diseases. As a result, one
      must consider carefully the conditions under which these therapeutics are
      manufactured if they are to be used in clinical studies or, ultimately, be
      approved as licensed cellular therapeutics. Here, we describe the principles
      behind the manufacturing of clinical-grade cellular products, as well as
      potential methods for large-scale expansion and processing according to Good
      Manufacturing Practice (GMP) standards sets by the United States Food and Drug
      Administration. Standards for personnel, materials, procedures, and facilities
      required for such manufacturing processes are reviewed. We also discuss current
      and future scale-up methods for the manufacturing of large doses of cellular
      therapeutics under GMP conditions and compare the use of conventional culture
      methods such as tissue culture flasks and multi-layered cell factories with novel
      systems such as closed system hollow-fiber bioreactors. Incorporation of these
      novel bioreactor systems into GMP facilities may enable us to provide adequate
      cell numbers for multi-center clinical trials and paves the way for development
      of cellular therapeutics with the potential to treat very large numbers of
      patients.

PMID- 24732772
TI  - Regulatory issues in cell-based therapy for clinical purposes.
AB  - Rapid development in the fields of cellular and molecular biology, biotechnology,
      and bioengineering medicine has brought new, highly innovative treatments and
      medicinal products, some of which contain viable cells and tissues associated
      with scaffolds and devices. These new cell-based therapy approaches in
      regenerative medicine have great potential for use in the treatment of a number
      of diseases that at present cannot be managed effectively. Given the unique
      challenges associated with the development of human cell-based medicinal
      products, great care is required in the development of procedures, practices, and
      regulation. In cell therapy, appropriate methodologies in the areas of
      production, reproducibility, maintenance, and delivery are essential for accurate
      definition and reliable assurance of the suitability and quality of the final
      products. Recently, the official European Community agencies (EMA) and the
      relevant authority in the USA (FDA) have made significant efforts to establish
      regulatory guidance for use in the application of the cell-based therapies for
      human patients. The guidelines surrounding cell-based therapy take into account
      the current legislation, but focus less on the heterogeneity and requirements of
      individual human cell-based products, including specific combination products and
      applications. When considering guidelines and regulation, a risk assessment
      approach is an effective method of identifying priority areas for the development
      of human cell-based medicinal products. Additionally, effective design and
      thorough validation of the manufacturing process in line with existing Good
      Manufacturing Practices (GMPs) and quality control regimes and a program that
      ensures the traceability and biovigilance of the final products are also all
      essential elements to consider.

PMID- 24732773
TI  - Cell-based therapy for retinal degenerative disease. Preface.

PMID- 24732774
TI  - Highly pathogenic adapted HIV-1 strains limit host immunity and dictate rapid
      disease progression.
AB  - OBJECTIVE: The study of HIV-1 rapid progressors has been limited to specific case
      reports. Nevertheless, identification and characterization of the viral and host
      factors involved in rapid progression are crucial when attempting to uncover the
      correlates of rapid disease outcome. DESIGN: We carried out comparative
      functional analyses in rapid progressors (n = 46) and standard progressors (n =
      46) early after HIV-1 seroconversion (<=1 year). The viral traits tested were
      viral replicative capacity, co-receptor usage, and genomic variation. Host CD8(+)
      T-cell responses, humoral activity, and HLA immunogenetic markers were also
      determined. RESULTS: Our data demonstrate an unusual convergence of highly
      pathogenic HIV-1 strains in rapid progressors. Compared with standard
      progressors, rapid progressor viral strains show higher in-vitro replicative
      capacity (81.5 vs. 67.9%; P = 0.025) and greater X4/DM co-receptor usage (26.3
      vs. 2.8%; P = 0.006) in early infection. Limited or absent functional HIV-1
      CD8(+) T-cell responses and neutralizing activity were measured in rapid
      progressors. Moreover, the increase in common HLA allele-restricted CD8(+) T-cell
      escape mutations in rapid progressors acts as a signature of uncontrolled HIV-1
      replication and early impairment of adaptive cellular responses. CONCLUSION: Our
      data support a dominant role for viral factors in rapid progressors. Robust HIV-1
      replication and intrinsic viral properties limit host adaptive immune responses,
      thus driving rapid disease progression.

PMID- 24732775
TI  - Employment status in persons with and without HIV infection in Denmark: 1996
      2011.
AB  - OBJECTIVE: To estimate annual employment rates and disability retirement rates
      (DRRs) among HIV-infected individuals and population controls during the period
      1996-2011. DESIGN: A population-based cohort study including all HIV-infected
      individuals born in Denmark and not reporting intravenous (i.v.) drug abuse as a
      route of HIV infection or diagnosed with hepatitis C infection (n = 2799) and
      22,369 individually matched persons from the background population. Study
      inclusion was 1 January 1996 or HIV diagnosis, which ever came last. METHODS:
      Data on employment status and disability pension were extracted from Danish
      national registries. Employment rate and DRR were estimated in each calendar year
      after study inclusion for the cohorts included before 1996 (pre-1996), 1996-1999
      and 2000-2011. RESULTS: Employment rate in the year of study inclusion increased
      from 54.8% [95% confidence interval (CI) 50.5-59.6] in the pre-1996 cohort to
      74.6% (66.9-83.2) and 77.4% (72.8-82.2) in the 1996-1999 and 2000-2011 cohorts,
      respectively, compared with 85.9-87.2% in the comparison cohorts. Five years from
      study inclusion, employment rates were 56.1 (51.4-61.1), 66.2 (58.7-74.6) and
      70.9% (65.0-77.3) in the pre-1996, 1996-1999 and 2000-2011 cohorts, respectively,
      compared with 82.5-85.6% in the comparison cohorts. Five years from study
      inclusion, DRRs were 32.3 (28.9-36.3) in the pre-1996 cohort and decreased to
      17.8 (14.1-22.4) and 11.6% (9.4-14.4) in the 1996-1999 and 2000-2011 cohorts,
      respectively, compared with 5.1-7.2% in the comparison cohorts. CONCLUSION: After
      the introduction of HAART, employment rates have increased profoundly among HIV
      infected individuals, but have remained lower than in the background population.
      During the same period, DRRs decreased among HIV-infected individuals, but still
      remained higher than in the background population.

PMID- 24732776
TI  - Ibudilast (AV411), and its AV1013 analog, reduce HIV-1 replication and neuronal
      death induced by HIV-1 and morphine.
AB  - OBJECTIVE: We explored the antiviral therapeutic potential of ibudilast (AV411,
      MN-166) and its amino analog, AV1013. METHODS: We analyzed whether Ibudilast, a
      nonselective cyclic AMP phosphodiesterase inhibitor that has been used clinically
      in Asia for bronchial asthma, poststroke dizziness, and ocular allergies, and
      AV1013, attenuate HIV-1 replication and the synergistic interactions seen with
      opiate abuse-HIV-1 comorbidity in neuronal death and inflammation. RESULTS: AV411
      and AV1013 inhibited replication by HIV-1 in microglia and significantly
      suppressed Tat +/- morphine-induced tumor necrosis factor-alpha and MIF
      production, the activation of the nuclear factor-kappa B subunit p65, and
      neuronal death. AV411 and AV1013 prevented HIV-1 replication, and attenuated
      tumor necrosis factor-alpha and MIF release at concentrations of 100  nmol/l and
      1  MUmol/l, which are likely achievable at clinical doses. More importantly, co
      exposure with morphine did not negate the inhibitory actions of AV411.
      CONCLUSION: Collectively, our data suggest that AV411 and its amino analog,
      AV1013, may be useful neuroprotective agents counteracting neurotoxicity caused
      by infected and activated glia, and implicate them as potential therapies for the
      management of HIV-associated neurocognitive disorders in an opioid-abusing
      population.

PMID- 24732777
TI  - Trib3 is developmentally and nutritionally regulated in the brain but is
      dispensable for spatial memory, fear conditioning and sensing of amino acid
      imbalanced diet.
AB  - Tribbles homolog 3 (TRIB3) is a mammalian pseudokinase that is induced in
      neuronal cell cultures in response to cell death-inducing stresses, including
      neurotrophic factor deprivation. TRIB3 is an inhibitor of activating
      transcription factor 4 (ATF4), the central transcriptional regulator in the
      eukaryotic translation initiation factor 2alpha (eIF2alpha) phosphorylation
      pathway that is involved in the cellular stress response and behavioral
      processes. In this article, we study the expression of Trib3 in the mouse brain,
      characterize the brain morphology of mice with a genetic ablation of Trib3 and
      investigate whether Trib3 deficiency alters eIF2alpha-dependent cognitive
      abilities. Our data show that the consumption of a leucine-deficient diet induces
      Trib3 expression in the anterior piriform cortex, the brain region responsible
      for detecting essential amino acid intake imbalance. However, the aversive
      response to leucine-devoid diet does not differ in Trib3 knockout and wild type
      mice. Trib3 deletion also does not affect long-term spatial memory and reversal
      learning in the Morris water maze and auditory or contextual fear conditioning.
      During embryonic development, Trib3 expression increases in the brain and
      persists in the early postnatal stadium. Neuroanatomical characterization of mice
      lacking Trib3 revealed enlarged lateral ventricles. Thus, although the absence of
      Trib3 does not alter the eIF2alpha pathway-dependent cognitive functions of
      several areas of the brain, including the hippocampus, amygdala and anterior
      piriform cortex, Trib3 may serve a role in other central nervous system processes
      and molecular pathways. 

PMID- 24732778
TI  - Insulin oversecretion in MSG-obese rats is related to alterations in cholinergic
      muscarinic receptor subtypes in pancreatic islets.
AB  - BACKGROUND/AIMS: Impaired pancreatic beta cell function and insulin
      secretion/action are a link between obesity and type 2 diabetes, which are
      worldwide public health burdens. We aimed to characterize the muscarinic
      acetylcholine receptor (mAChR) M1-M4 subtypes in isolated pancreatic islets from
      pre-diabetic obese rats that had been treated neonatally with monosodium L
      glutamate (MSG). METHODS: At 90 days of age, both the MSG and the control groups
      underwent biometric and biochemical evaluation. Anti-muscarinic drugs were used
      to study mAChR function either in vivo or in vitro. RESULTS: The results
      demonstrated that atropine treatment reduced insulin secretion in the MSG-treated
      and control groups, whereas treatment with an M2mAChR-selective antagonist
      increased secretion. Moreover, the insulinostatic effect of an M3mAChR-selective
      antagonist was significantly higher in the MSG-treated group. M1mAChR and M3mAChR
      expression was increased in the MSG-obese group by 55% and 73%, respectively. In
      contrast, M2mAChR expression decreased by 25% in the MSG group, whereas M4mAChR
      expression was unchanged. CONCLUSIONS: Functional changes in and altered content
      of the mAChR (M1-M4) subtypes are pivotal to the demand for high pancreatic beta
      cell insulin secretion in MSG-obese rats, which is directly associated with vagal
      hyperactivity and peripheral insulin resistance.

PMID- 24732779
TI  - Mouse genetic background influences the dental phenotype.
AB  - Dental enamel covers the crown of the vertebrate tooth and is considered to be
      the hardest tissue in the body. Enamel develops during secretion of an
      extracellular matrix by ameloblast cells in the tooth germ, prior to eruption of
      the tooth into the oral cavity. Secreted enamel proteins direct mineralization
      patterns during the maturation stage of amelogenesis as the tooth prepares to
      erupt. The amelogenins are the most abundant enamel proteins and are required for
      normal enamel development. Phenotypic differences were observed between incisors
      from individual Amelx (amelogenin) null mice that had a mixed 129xC57BL/6J
      genetic background and between inbred wild-type (WT) mice with different genetic
      backgrounds (C57BL/6J, C3H/HeJ, FVB/NJ). We hypothesized that this could be due
      to modifier genes, as human patients with a mutation in an enamel protein gene
      causing the enamel defect amelogenesis imperfecta (AI) can also have varied
      appearance of dentitions within a kindred. Enamel density measurements varied for
      all WT inbred strains midway during incisor development. Enamel thickness varied
      between some WT strains, and, unexpectedly, dentin density varied extensively
      between incisors and molars of all WT and Amelx null strains studied. WTFVB/NJ
      incisors were more similar to those of Amelx null mice than to those of the other
      WT strains in terms of incisor height/width ratio and pattern of enamel
      mineralization. Strain-specific differences led to the conclusion that modifier
      genes may be implicated in determining both normal development and severity of
      enamel appearance in AI mouse models and may in future studies be related to
      phenotypic heterogeneity within human AI kindreds reported in the literature.

PMID- 24732780
TI  - Isolated clonal cytogenetic abnormalities after high-dose therapy.
AB  - Therapy-related myeloid neoplasms (t-MN) are well-recognized complications of
      high-dose cytotoxic therapy (HDT), such as autologous stem cell transplantation
      (ASCT). Clonal marrow cytogenetic abnormalities (CMCA) in the setting of normal
      bone marrow pathology have also been reported after HDT, but their significance
      remains unclear. We retrospectively evaluated occurrences of CMCA and t-MN in 785
      patients treated with HDT at Johns Hopkins University between 1997 and 2007. Most
      patients received ASCT, but 106 patients who received high-dose cyclophosphamide
      without ASCT were also included in this study, as this is our institutional
      standard for malignant and nonmalignant lymphoproliferative disorders in need of
      HDT. Twenty-two patients developed t-MN, with an estimated cumulative incidence
      of 3.5% at 4 years. Eleven patients developed isolated CMCA, either transient or
      persistent without pathologic evidence of t-MN. Altogether, only 20 of the
      patients with reported CMCA subsequently developed t-MN during the follow-up
      period. Therefore, in the absence of pathologic evidence of t-MN, CMCA should not
      be considered diagnostic of t-MN. 

PMID- 24732781
TI  - Viral respiratory infections diagnosed by multiplex PCR after allogeneic
      hematopoietic stem cell transplantation: long-term incidence and outcome.
AB  - Viral respiratory infections (VRIs) are frequent after hematopoietic stem cell
      transplantation and constitute a potential cause of mortality. We analyzed the
      incidence, risk factors, and prognosis of VRIs in a cohort of transplanted
      patients. More frequent viruses were human coronavirus and human rhinovirus
      followed by flu-like viruses and adenovirus. Risk factors for death were
      lymphocytopenia and high steroid dosage. 

PMID- 24732782
TI  - Mixed chimerism: good news or bad news?

PMID- 24732783
TI  - Covert anti-compensatory quick eye movements during head impulses.
AB  - BACKGROUND: Catch-up saccades during passive head movements, which compensate for
      a deficient vestibulo-ocular reflex (VOR), are a well-known phenomenon. These
      quick eye movements are directed toward the target in the opposite direction of
      the head movement. Recently, quick eye movements in the direction of the head
      movement (covert anti-compensatory quick eye movements, CAQEM) were observed in
      older individuals. Here, we characterize these quick eye movements, their
      pathophysiology, and clinical relevance during head impulse testing (HIT).
      METHODS: Video head impulse test data from 266 patients of a tertiary vertigo
      center were retrospectively analyzed. Forty-three of these patients had been
      diagnosed with vestibular migraine, and 35 with Meniere's disease. RESULTS: CAQEM
      occurred in 38% of the patients. The mean CAQEM occurrence rate (per HIT trial)
      was 11+/-10% (mean+/-SD). Latency was 83+/-30 ms. CAQEM followed the saccade main
      sequence characteristics and were compensated by catch-up saccades in the
      opposite direction. Compensatory saccades did not lead to more false pathological
      clinical head impulse test assessments (specificity with CAQEM: 87%, and without:
      85%). CAQEM on one side were associated with a lower VOR gain on the
      contralateral side (p<0.004) and helped distinguish Meniere's disease from
      vestibular migraine (p = 0.01). CONCLUSION: CAQEM are a common phenomenon, most
      likely caused by a saccadic/quick phase mechanism due to gain asymmetries. They
      could help differentiate two of the most common causes of recurrent vertigo:
      vestibular migraine and Meniere's disease.

PMID- 24732784
TI  - Effects of equal-volume resistance training performed one or two times a week in
      upper body muscle size and strength of untrained young men.
AB  - AIM: The purpose of the present study was to compare the effects of equal-volume
      resistance training (RT) performed once or twice a week on muscle mass and
      strength of the elbow flexors in untrained young men. METHODS: Thirty men (23 +/-
      3 years) without previous resistance training experience were divided into two
      groups: Group 1 (G1) trained each muscle group only once a week and group 2 (G2)
      trained each muscle twice a week during 10 weeks. Baseline and 10 weeks post-test
      elbow flexors muscle thickness (MT) were measured using a B-Mode ultrasound. Peak
      torque (PT) was assessed by an isokinetic dynamometer before and after the
      training program. RESULTS: Elbow flexors MT increased significantly (P<0.05) from
      31.70 +/- 3.31 to 33.43 +/- 3.46 mm in G1, and from 32.78 +/- 4.03 to 35.09 +/-
      3.55 mm in G2. Elbow flexors PT also increased (P<0.05) from 50.77 +/- 9.26 to
      54.15 +/- 10.79 N.m in G1, and from 48.99 +/- 11.52 to 55.29 +/- 10.24 N.m in G2.
      The results of ANOVA did not reveal group by time interactions for any variable,
      indicating no difference between groups for the changes in MT or PT. CONCLUSION:
      The results from the present study suggest that untrained men experience similar
      gains in muscle mass and strength with equal volume RT performed one or two days
      per week.

PMID- 24732785
TI  - Does Bus Rapid Transit promote walking? An examination of New York City's Select
      Bus Service.
AB  - BACKGROUND: Cities across the U.S. and internationally are adopting Bus Rapid
      Transit to improve transit services for residents. Features of Bus Rapid Transit
      include fewer stops, dedicated bus lanes, and expedited systems for boarding
      busses, compared with regular bus service. This study examines whether Bus Rapid
      Transit (BRT) ridership is associated with increased rates of walking, because of
      the greater distance between BRT stops compared with regular bus service.
      METHODS: Surveys were conducted with riders of local and BRT buses for New York
      City's M15 Select Bus Service line. Surveys examined bus ridership, health status
      and physical activity, walking rates, and demographic information. RESULTS: BRT
      riders reported walking approximately half a block more than did local bus
      riders. The average number of blocks walked decreased for BRT riders who
      previously used the subway before the implementation of the BRT. CONCLUSIONS: BRT
      may be a useful tool to support walking for some groups. Depending on where it is
      implemented, BRT may also be associated with reduced walking among users who
      switch to BRT from other active transportation modes. Future research should
      examine associations between walking and BRT ridership with a larger sample and
      more sites.

PMID- 24732786
TI  - Probable Association of an Attack of Bilateral Acute Angle-Closure Glaucoma With
      Duloxetine.
AB  - OBJECTIVE: To report a patient who had an attack of bilateral acute angle-closure
      glaucoma (ACG) probably associated with the use of duloxetine. CASE SUMMARY: The
      case reported here involves an 81-year-old Caucasian woman whose past ocular
      history was unremarkable except for high hyperopia and cataract. The patient
      developed ocular symptoms 2 days after starting duloxetine, a serotonin
      norepinephrine reuptake inhibitor (SNRI) and was diagnosed with acute ACG. The
      elevated intraocular pressure (IOP) was successfully lowered with medical
      treatment, and the patient was advised to discontinue duloxetine. She
      subsequently underwent laser iridotomy in both eyes, and her IOP remained
      adequately controlled. A score of 6 was obtained using the Naranjo adverse drug
      reaction probability scale, suggesting duloxetine as the probable cause of the
      attack of ACG in this patient. DISCUSSION: There are a few previous reports of
      acute ACG associated with venlafaxine, another member of the class of SNRIs. In
      addition, there are several reports of ACG associated with members of the related
      class of selective serotonin reuptake inhibitors (SSRIs)-namely, fluoxetine,
      paroxetine, fluvoxamine, sertraline, citalopram, and escitalopram. The mechanism
      responsible for the precipitation of ACG by members of these 2 classes of drugs
      is likely a result of mydriasis caused by their adrenergic effects, weak
      anticholinergic activities, or the increased levels of serotonin. CONCLUSION:
      Because the SNRIs, including duloxetine, and SSRIs are commonly used in the
      management of depression or chronic pain, caution is warranted with the use of
      these drugs in patients with risk factors for ACG.

PMID- 24732787
TI  - Bupropion and Escitalopram During Lactation.
AB  - OBJECTIVE: To report a case of seizure-like symptoms in an infant exposed to
      bupropion and escitalopram through breastfeeding. CASE SUMMARY: A 6.5-month-old
      female infant, breastfed by a mother treated with bupropion XL 150 mg/d and
      escitalopram 10 mg/d for depression, presented to our hospital with severe emesis
      and tonic seizure-like symptoms. The symptoms resolved with supportive therapy.
      Urine toxicology screen in the infant revealed bupropion and escitalopram.
      Bupropion, and its active metabolite, hydroxybupropion, were analyzed and
      quantified both in the infant's serum and in the breast milk. Diagnostic workup
      for seizure etiologies was otherwise negative. After being asymptomatic for 48
      hours, her discharge diagnosis was adverse events associated with bupropion and
      escitalopram in lactation. An objective causality assessment (Naranjo assessment)
      revealed that this adverse effect was probable. DISCUSSION: The adverse events in
      our case were associated with serum concentrations of bupropion and
      hydroxybupropion that are lower than the reported therapeutic range, perhaps
      suggesting that infants, compared with adults, may have a higher susceptibility
      to the epileptogenic effects of bupropion and/or hydroxybupropion. Furthermore,
      although we do not have escitalopram serum concentrations, this drug interaction
      may have had a contributing role in this case, possibly because of cytochrome
      P4502D6 inhibition by bupropion and metabolites. CONCLUSION: As the number of
      reproductive-aged women requiring polytherapy to control their depression is
      increasing, further research is needed to establish the safety of combined
      antidepressants, such as selective serotonin reuptake inhibitors and bupropion,
      during lactation.

PMID- 24732788
TI  - Role of serum vaspin in progression of type 2 diabetes: a 2-year cohort study.
AB  - Vaspin is a novel adipocytokine that has potential insulin-sensitizing effects.
      The aim of this study is to explore the role of vaspin in the progression of type
      2 diabetes mellitus (T2DM) in humans through a longitudinal process. This was a 2
      year follow-up study that included 132 patients with T2DM and 170 non-diabetic
      subjects. The serum vaspin and adiponectin levels were determined with ELISA.
      Anthropometric measurements, circulating glucose, hemoglobin A1c, insulin level,
      liver function, kidney function, and lipid profile were measured for each
      participant. The new onset of T2DM was counted in non-diabetic subjects and the
      glycemic control was analyzed in T2DM patients at follow-up. At enrollment, the
      serum vaspin and adiponectin levels were lower in T2DM patients compared with non
      diabetic subjects. Significant positive correlation between serum vaspin and HDL
      C levels (r = 0.23, P = 0.006) was observed in non-diabetic controls. The serum
      vaspin concentration was also significantly correlated with body mass index (BMI)
      (r = 0.19, P = 0.028), waist-hip ratio (WHR) (r = 0.17, P = 0.035) and
      homeostasis model assessment of insulin resistance (HOMA-IR) (r = 0.14, P =
      0.029) in T2DM patients. In cohort analyses, it was found that lower serum vaspin
      [odds ratio (OR) = 0.52, 95% confidence interval (CI): 0.10-0.87, P = 0.015] and
      adiponectin (OR = 0.35, 95% CI: 0.20-0.72, P = 0.015) levels at baseline were
      risk factors for new onset of T2DM at follow-up. The percentage of insulin
      treatment in T2DM patients was higher in the sub-group with lower serum vaspin
      level than that in the sub-group with higher vaspin level at follow-up (55.3% vs.
      44.7%, P = 0.020). Our study indicates that low serum concentration of vaspin is
      a risk factor for the progression of T2DM. 

PMID- 24732789
TI  - Biomechanical analysis of the human finger extensor mechanism during isometric
      pressing.
AB  - This study investigated the effects of the finger extensor mechanism on the bone
      to-bone contact forces at the interphalangeal and metacarpal joints and also on
      the forces in the intrinsic and extrinsic muscles during finger pressing. This
      was done with finger postures ranging from very flexed to fully extended. The
      role of the finger extensor mechanism was investigated by using two alternative
      finger models, one which omitted the extensor mechanism and another which
      included it. A six-camera three-dimensional motion analysis system was used to
      capture the finger posture during maximum voluntary isometric pressing. The
      fingertip loads were recorded simultaneously using a force plate system. Two
      three-dimensional biomechanical finger models, a minimal model without extensor
      mechanism and a full model with extensor mechanism (tendon network), were used to
      calculate the joint bone-to-bone contact forces and the extrinsic and intrinsic
      muscle forces. If the full model is assumed to be realistic, then the results
      suggest some useful biomechanical advantages provided by the tendon network of
      the extensor mechanism. It was found that the forces in the intrinsic muscles
      (interosseus group and lumbrical) are significantly reduced by 22% to 61% due to
      the action of the extensor mechanism, with the greatest reductions in more flexed
      postures. The bone-to-bone contact force at the MCP joint is reduced by 10% to
      41%. This suggests that the extensor mechanism may help to reduce the risk of
      injury at the finger joints and also to moderate the forces in intrinsic muscles.
      These apparent biomechanical advantages may be a result of the extensor
      mechanism's distinctive interconnected fibrous structure, through which the
      contraction of the intrinsic muscles as flexors of the MCP joint can generate
      extensions at the DIP and PIP joints. 

PMID- 24732790
TI  - Discovery of small molecular (D)-leucinamides as potent, Notch-sparing gamma
      secretase modulators.
AB  - Structural optimization of the prior lead 3 led to the small molecular (D)
      leucinamides with potent modulating activity and Notch-sparing selectivity on the
      proteolytic processing of amyloid-beta precursor proteins. The N-(R)-epoxypropyl
      analog 10c exhibited potent gamma-secretase modulation compared to DAPT and
      showed substantial substrate selection for APP cleavage over Notch cleavage,
      while N-(2-fluoro)benzyl analog 10e showed the most potent gamma-secretase
      inhibition with dull selectivity. The exceptional suppression of ERK-mediated
      activation suggested that these potent gamma-secretase modulators may adapt an
      alternative pathway to prominently induce the differential inhibition of C99
      cleavage by gamma-secretase.

PMID- 24732791
TI  - Synthesis, radiolabeling and in vivo evaluation of [(11)C](R)-1-[4-[2-(4
      methoxyphenyl)phenyl]piperazin-1-yl]-3-(2-pyrazinyloxy)-2-propanol, a potential
      PET radioligand for the 5-HT(7) receptor.
AB  - In the search for a novel serotonin 7 (5-HT7) receptor PET radioligand we
      synthesized and evaluated a new series of biphenylpiperazine derivatives in
      vitro. Among the studied compounds, (R)-1-[4-[2-(4-methoxyphenyl)phenyl]piperazin
      1-yl]-3-(2-pyrazinyloxy)-2-propanol ((R)-16), showed the best combination of
      affinity, selectivity, and lipophilicity, and was thus chosen for carbon-11
      labelling and evaluation in pigs. After intravenous injection, [(11)C](R)-16
      entered the pig brain and displayed reversible tracer kinetics. Pretreatment with
      the 5-HT7 receptor selective antagonist SB-269970 (1) resulted in limited
      decrease in the binding of [(11)C](R)-16, suggesting that this radioligand is not
      optimal for imaging the brain 5-HT7 receptor in vivo but it may serve as a lead
      compound for the design of novel 5-HT7 receptor PET radioligands. 

PMID- 24732792
TI  - Gold(I) complexes with alkylated PTA (1,3,5-triaza-7-phosphaadamantane)
      phosphanes as anticancer metallodrugs.
AB  - New stable thiolate gold(I) derivatives containing the alkylated phosphanes [PTA
      CH2Ph]Br and [PTA-CH2COOMe]Br derived from 1,3,5-triaza-7-phosphaadamantane (PTA)
      have been prepared by different routes of synthesis. By the use of basic media to
      deprotonate the corresponding thiol in the former and by transmetallation
      reactions from tin (IV) complexes, in the later, thus avoiding side reactions on
      the phosphane. Strong antiproliferative effects are observed for most of the
      compounds, including the chloro- and bromo precursors with the series of
      phosphanes derived from PTA, in human colon cancer cell lines (Caco-2, PD7 and
      TC7 clones). Apoptosis-induced cell death is found for all compounds, being the
      thiolate derivatives with [PTA-CH2Ph]Br the most effective, as shown by an
      annexin-V/propidium iodide double-staining assay.

PMID- 24732793
TI  - The acyclic retinoid Peretinoin inhibits hepatitis C virus replication and
      infectious virus release in vitro.
AB  - Clinical studies suggest that the oral acyclic retinoid Peretinoin may reduce the
      recurrence of hepatocellular carcinoma (HCC) following surgical ablation of
      primary tumours. Since hepatitis C virus (HCV) infection is a major cause of HCC,
      we assessed whether Peretinoin and other retinoids have any effect on HCV
      infection. For this purpose, we measured the effects of several retinoids on the
      replication of genotype 1a, 1b, and 2a HCV in vitro. Peretinoin inhibited RNA
      replication for all genotypes and showed the strongest antiviral effect among the
      retinoids tested. Furthermore, it reduced infectious virus release by 80-90%
      without affecting virus assembly. These effects could be due to reduced
      signalling from lipid droplets, triglyceride abundance, and the expression of
      mature sterol regulatory element-binding protein 1c and fatty acid synthase.
      These negative effects of Peretinoin on HCV infection may be beneficial in
      addition to its potential for HCC chemoprevention in HCV-infected patients. 

PMID- 24732794
TI  - A novel RNA motif mediates the strict nuclear localization of a long noncoding
      RNA.
AB  - The ubiquitous presence of long noncoding RNAs (lncRNAs) in eukaryotes points to
      the importance of understanding how their sequences impact function. As many
      lncRNAs regulate nuclear events and thus must localize to nuclei, we analyzed the
      sequence requirements for nuclear localization in an intergenic lncRNA named BORG
      (BMP2-OP1-responsive gene), which is both spliced and polyadenylated but is
      strictly localized in nuclei. Subcellular localization of BORG was not dependent
      on the context or level of its expression or decay but rather depended on the
      sequence of the mature, spliced transcript. Mutational analyses indicated that
      nuclear localization of BORG was mediated through a novel RNA motif consisting of
      the pentamer sequence AGCCC with sequence restrictions at positions -8 (T or A)
      and -3 (G or C) relative to the first nucleotide of the pentamer. Mutation of the
      motif to a scrambled sequence resulted in complete loss of nuclear localization,
      while addition of even a single copy of the motif to a cytoplasmically localized
      RNA was sufficient to impart nuclear localization. Further, the presence of this
      motif in other cellular RNAs showed a direct correlation with nuclear
      localization, suggesting that the motif may act as a general nuclear localization
      signal for cellular RNAs. 

PMID- 24732795
TI  - The transcription factors Tec1 and Ste12 interact with coregulators Msa1 and Msa2
      to activate adhesion and multicellular development.
AB  - In Saccharomyces cerevisiae and related yeast species, the TEA transcription
      factor Tec1, together with a second transcription factor, Ste12, controls
      development, including cell adhesion and filament formation. Tec1-Ste12 complexes
      control target genes through Tec1 binding sites (TEA consensus sequences [TCSs])
      that can be further combined with Ste12 binding sites (pheromone response
      elements [PREs]) for cooperative DNA binding. The activity of Tec1-Ste12
      complexes is known to be under negative control of the Dig1 and Dig2 (Dig1/2)
      transcriptional corepressors that confer regulation by upstream signaling
      pathways. Here, we found that Tec1 and Ste12 can associate with the
      transcriptional coregulators Msa1 and Msa2 (Msa1/2), which were previously found
      to associate with the cell cycle transcription factor complexes SBF (Swi4/Swi6
      cell cycle box binding factor) and MBF (Mbp1/Swi6 cell cycle box binding factor)
      to control G1-specific transcription. We further show that Tec1-Ste12-Msa1/2
      complexes (i) do not contain Swi4 or Mbp1, (ii) assemble at single TCSs or
      combined TCS-PREs in vitro, and (iii) coregulate genes involved in adhesive and
      filamentous growth by direct promoter binding in vivo. Finally, we found that, in
      contrast to Dig proteins, Msa1/2 seem to act as coactivators that enhance the
      transcriptional activity of Tec1-Ste12. Taken together, our findings add an
      additional layer of complexity to our understanding of the control mechanisms
      exerted by the evolutionarily conserved TEA domain and Ste12-like transcription
      factors. 

PMID- 24732796
TI  - A conserved loop in the catalytic domain of eukaryotic elongation factor 2 kinase
      plays a key role in its substrate specificity.
AB  - Eukaryotic elongation factor 2 kinase (eEF2K) is the best-characterized member of
      the alpha-kinase family. Within this group, only eEF2K and myosin heavy chain
      kinases (MHCKs) have known substrates. Here we have studied the roles of specific
      residues, selected on the basis of structural data for MHCK A and TRPM7, in the
      function of eEF2K. Our data provide the first information regarding the basis of
      the substrate specificity of alpha-kinases, in particular the roles of residues
      in the so-called N/D loop, which appears to occupy a position in the structure of
      alpha-kinases similar to that of the activation loop in other kinases. Several
      mutations in the EEF2K gene occur in tumors, one of which (Arg303Cys) is at a
      highly conserved residue in the N/D loop. This mutation greatly enhances eEF2K
      activity and may be cytoprotective. Our data support the concept that the major
      autophosphorylation site (Thr348 in eEF2K) docks into a binding pocket to help
      create the kinase-competent conformation. This is similar to the situation for
      MHCK A and is consistent with this being a common feature of alpha-kinases. 

PMID- 24732797
TI  - RASSF1A inactivation unleashes a tumor suppressor/oncogene cascade with context
      dependent consequences on cell cycle progression.
AB  - The RASSF1A gene is one of the most frequently inactivated genes in over 30
      different types of cancers (H. Donninger, M. D. Vos, and G. J. Clark, J. Cell
      Sci. 120:3163-3172, 2007, http://dx.doi.org/10.1242/jcs.010389). Despite the
      prevalence of RASSF1A silencing in human cancer, the mechanism by which RASSF1A
      functions as a tumor suppressor is not well understood. Characterization of the
      consequences of RASSF1A loss on epithelial cell proliferation revealed that
      RASSF1A expression suppresses both microRNA 21 (miR-21) expression and
      extracellular signal-regulated kinase 1/2 (ERK1/2) activation. The mechanism of
      the former is through restraint of SCF(betaTrCP)-dependent destruction of the
      repressor element 1 silencing transcription factor (REST) tumor suppressor and
      consequent inhibition of miR-21 promoter activation. The mechanism of the latter
      is through physical sequestration of MST2, which results in accumulation of
      inactivating S259 phosphorylation of RAF1. Whether or not inactivation of these
      RASSF1A regulatory relationships can unleash enhanced proliferative capacity is
      dependent upon the coupling of SCF(betaTrCP) and miR-21 to suppression of SKP2
      protein translation and stability. Airway epithelial cultures retain this
      coupling and therefore respond to RASSF1A inactivation by p27-dependent cell
      cycle arrest. In contrast, colonic crypt-derived epithelial cells have uncoupled
      SCF(betaTrCP) from SKP2 and respond to RASSF1A inactivation by enhanced
      proliferation rates. These observations help account for context-specific
      molecular etiology of oncogenic transformation and suggest intervention
      strategies for recently developed SKP2 inhibitors. 

PMID- 24732798
TI  - Suv39h1 mediates AP-2alpha-dependent inhibition of C/EBPalpha expression during
      adipogenesis.
AB  - Previous studies have shown that CCAAT/enhancer-binding protein alpha
      (C/EBPalpha) plays a very important role during adipocyte terminal
      differentiation and that AP-2alpha (activator protein 2alpha) acts as a repressor
      to delay the expression of C/EBPalpha. However, the mechanisms by which AP-2alpha
      prevents the expression of C/EBPalpha are not fully understood. Here, we present
      evidence that Suv39h1, a histone H3 lysine 9 (H3K9)-specific
      trimethyltransferase, and G9a, a euchromatic methyltransferase, both interact
      with AP-2alpha and enhance AP-2alpha-mediated transcriptional repression of
      C/EBPalpha. Interestingly, we discovered that G9a mediates dimethylation of H3K9,
      thus providing the substrate, which is methylated by Suv39h1, to H3K9me3 on the
      C/EBPalpha promoter. The expression level of AP-2alpha was consistent with
      enrichment of H3K9me2 and H3K9me3 on the C/EBPalpha promoter in 3T3-L1
      preadipocytes. Knockdown of Suv39h markedly increased C/EBPalpha expression and
      promoted adipogenesis. Conversely, ectopic expression of Suv39h1 delayed
      C/EBPalpha expression and impaired the accumulation of triglyceride, while
      simultaneous knockdown of AP-2alpha or G9a partially rescued this process. These
      findings indicate that Suv39h1 enhances AP-2alpha-mediated transcriptional
      repression of C/EBPalpha in an epigenetic manner and further inhibits adipocyte
      differentiation. 

PMID- 24732799
TI  - KSRP and MicroRNA 145 are negative regulators of lipolysis in white adipose
      tissue.
AB  - White adipose tissue (WAT) releases fatty acids from stored triacylglycerol for
      an energy source. Here, we report that targeted deletion of KH-type splicing
      regulatory protein (KSRP), an RNA-binding protein that regulates gene expression
      at multiple levels, enhances lipolysis in epididymal WAT (eWAT) because of the
      upregulation of genes promoting lipolytic activity. Expression of microRNA 145
      (miR-145) is decreased because of impaired primary miR-145 processing in Ksrp(-/
      ) eWAT. We show that miR-145 directly targets and represses Foxo1 and Cgi58,
      activators of lipolytic activity, and forced expression of miR-145 attenuates
      lipolysis. This study reveals a novel in vivo function of KSRP in controlling
      adipose lipolysis through posttranscriptional regulation of miR-145 expression. 

PMID- 24732801
TI  - Retraction for Li et al., "ATAD3 Is a Limiting Factor in Mitochondrial Biogenesis
      and Adipogenesis of White Adipocyte-Like 3T3-L1 Cells".

PMID- 24732800
TI  - CtBP and associated LSD1 are required for transcriptional activation by NeuroD1
      in gastrointestinal endocrine cells.
AB  - Gene expression programs required for differentiation depend on both DNA-bound
      transcription factors and surrounding histone modifications. Expression of the
      basic helix-loop-helix (bHLH) protein NeuroD1 is restricted to endocrine cells in
      the gastrointestinal (GI) tract, where it is important for endocrine
      differentiation. RREB1 (RAS-responsive element binding protein 1), identified as
      a component of the CtBP corepressor complex, binds to nearby DNA elements to
      associate with NeuroD and potentiate transcription of a NeuroD1 target gene.
      Transcriptional activation by RREB1 depends on recruitment of CtBP with its
      associated proteins, including LSD1, through its PXDLS motifs. The mechanism of
      transcriptional activation by CtBP has not been previously characterized. Here we
      found that activation was dependent on the histone H3 lysine 9 (H3K9) demethylase
      activity of LSD1, which removes repressive methyl marks from dimethylated H3K9
      (H3K9Me2), to facilitate subsequent H3K9 acetylation by the NeuroD1-associated
      histone acetyltransferase, P300/CBP-associated factor (PCAF). The secretin, beta
      glucokinase, insulin I, and insulin II genes, four known direct targets of
      NeuroD1 in intestinal and pancreatic endocrine cells, all show similar promoter
      occupancy by CtBP-associated proteins and PCAF, with acetylation of H3K9. This
      work may indicate a mechanism for selective regulation of transcription by CtBP
      and LSD1 involving their association with specific transcription factors and
      cofactors to drive tissue-specific transcription. 

PMID- 24732802
TI  - Targeted activation of conventional and novel protein kinases C through
      differential translocation patterns.
AB  - Activation of the two ubiquitous families of protein kinases, protein kinase A
      (PKA) and protein kinase C (PKC), is thought to be independently coupled to
      stimulation of Galphas and Galphaq, respectively. Live-cell confocal imaging of
      protein kinase C fluorescent protein fusion constructs revealed that simultaneous
      activation of Galphas and Galphaq resulted in a differential translocation of the
      conventional PKCalpha to the plasma membrane while the novel PKCdelta was
      recruited to the membrane of the endoplasmic reticulum (ER). We demonstrate that
      the PKCdelta translocation was driven by a novel Galphas-cyclic AMP-EPAC-RAP
      PLCepsilon pathway resulting in specific diacylglycerol production at the
      membrane of the ER. Membrane-specific phosphorylation sensors revealed that
      directed translocation resulted in phosphorylation activity confined to the
      target membrane. Specific stimulation of PKCdelta caused phosphorylation of the
      inositol-1,4,5-trisphosphate receptor and dampening of global Ca(2+) signaling
      revealed by graded flash photolysis of caged inositol-1,4,5-trisphosphate. Our
      data demonstrate a novel signaling pathway enabling differential decoding of
      incoming stimuli into PKC isoform-specific membrane targeting, significantly
      enhancing the versatility of cyclic AMP signaling, thus demonstrating the
      possible interconnection between the PKA and PKC pathways traditionally treated
      independently. We thus provide novel and elementary understanding and insights
      into intracellular signaling events. 

PMID- 24732803
TI  - Thioesterase superfamily member 2 (Them2) and phosphatidylcholine transfer
      protein (PC-TP) interact to promote fatty acid oxidation and control glucose
      utilization.
AB  - Thioesterase superfamily member 2 (Them2) is a mitochondrion-associated long
      chain fatty acyl coenzyme A (CoA) thioesterase that is highly expressed in the
      liver and oxidative tissues. Them2 activity in vitro is increased when it
      interacts with phosphatidylcholine transfer protein (PC-TP), a cytosolic lipid
      binding protein. Them2-/- and Pctp-/- mice exhibit enhanced hepatic insulin
      sensitivity and increased adaptive thermogenesis, and Them2-/- mice are also
      resistant to diet-induced hepatic steatosis. Although we showed previously that a
      Them2-PC-TP complex suppresses insulin signaling, the enzymatic activity of Them2
      suggests additional direct involvement in regulating hepatic nutrient
      homeostasis. Here we used cultured primary hepatocytes to elucidate biochemical
      and cellular mechanisms by which Them2 and PC-TP regulate lipid and glucose
      metabolism. Under conditions simulating fasting, Them2-/- and Pctp-/- hepatocytes
      each exhibited decreased rates of fatty acid oxidation and gluconeogenesis. In
      results indicative of Them2-dependent regulation by PC-TP, chemical inhibition of
      PC-TP failed to reproduce these changes in Them2-/- hepatocytes. In contrast,
      rates of glucose oxidation and lipogenesis in the presence of high glucose
      concentrations were decreased only in Them2-/- hepatocytes. These findings reveal
      a primary role for Them2 in promoting mitochondrial oxidation of fatty acids and
      glucose in the liver.

PMID- 24732804
TI  - Mechanism of action of phenethylisothiocyanate and other reactive oxygen species
      inducing anticancer agents.
AB  - Reactive oxygen species (ROS)-inducing anticancer agents such as
      phenethylisothiocyanate (PEITC) activate stress pathways for killing cancer
      cells. Here we demonstrate that PEITC-induced ROS decreased expression of
      microRNA 27a (miR-27a)/miR-20a:miR-17-5p and induced miR-regulated ZBTB10/ZBTB4
      and ZBTB34 transcriptional repressors, which, in turn, downregulate specificity
      protein (Sp) transcription factors (TFs) Sp1, Sp3, and Sp4 in pancreatic cancer
      cells. Decreased expression of miR-27a/miR-20a:miR-17-5p by PEITC-induced ROS is
      a key step in triggering the miR-ZBTB Sp cascade leading to downregulation of Sp
      TFs, and this is due to ROS-dependent epigenetic effects associated with genome
      wide shifts in repressor complexes, resulting in decreased expression of Myc and
      the Myc-regulated miRs. Knockdown of Sp1 alone by RNA interference also induced
      apoptosis and decreased pancreatic cancer cell growth and invasion, indicating
      that downregulation of Sp transcription factors is an important common mechanism
      of action for PEITC and other ROS-inducing anticancer agents. 

PMID- 24732806
TI  - A natural unification of GNM and ANM and the role of inter-residue forces.
AB  - The Gaussian network model (GNM) and anisotropic network model (ANM) are two
      elastic network models that have been widely used to study protein fluctuation
      dynamics. Both models have strengths and weaknesses. Attempts have been made in
      the past to unify the two models but they had severe limitations. This work
      presents a novel theoretical result that shows how GNM and ANM can be unified
      through taking into account the effect of inter-residue forces. The unified
      model, called the force spring model, or FSM, is reduced to ANM when all the
      inter-residue forces are set to zero. Moreover, the unification reveals the role
      of inter-residue forces in protein fluctuation dynamics. Specifically, the effect
      of inter-residue forces is closely examined by studying the changes in mean
      square fluctuations when inter-residue forces are present. 

PMID- 24732805
TI  - Yeast DEAD box protein Mss116p is a transcription elongation factor that
      modulates the activity of mitochondrial RNA polymerase.
AB  - DEAD box proteins have been widely implicated in regulation of gene expression.
      Here, we show that the yeast Saccharomyces cerevisiae DEAD box protein Mss116p,
      previously known as a mitochondrial splicing factor, also acts as a transcription
      factor that modulates the activity of the single-subunit mitochondrial RNA
      polymerase encoded by RPO41. Binding of Mss116p stabilizes paused mitochondrial
      RNA polymerase elongation complexes in vitro and favors the posttranslocated
      state of the enzyme, resulting in a lower concentration of nucleotide substrate
      required to escape the pause; this mechanism of action is similar to that of
      elongation factors that enhance the processivity of multisubunit RNA polymerases.
      In a yeast strain in which the RNA splicing-related functions of Mss116p are
      dispensable, overexpression of RPO41 or MSS116 increases cell survival from
      colonies that were exposed to low temperature, suggesting a role for Mss116p in
      enhancing the efficiency of mitochondrial transcription under stress conditions. 

PMID- 24732807
TI  - Evidence of brain tumor stem progenitor-like cells with low proliferative
      capacity in human benign pituitary adenoma.
AB  - Tumor stem cells have been implicated as cancer-initiating cells in malignant
      brain tumors. However, whether benign brain tumors also contain tumor stem cells
      are largely unexplored. Here, we investigated whether tumor stem-like cells were
      present in pituitary adenoma similar to malignant brain tumors. By
      immunocytochemistry, we found that pituitary adenoma tissues expressed neural
      stem cell marker. These cells could form neurospheres in vitro, expressed neural
      stem/progenitor cell markers and generated daughter cells with the capacity to
      differentiate into three neural lineages. Importantly, compared with non-invasive
      pituitary adenomas, we found that CD133 expression was significantly increased in
      invasive pituitary adenomas, suggesting that the proliferative capacity was
      correlated with the malignance of pituitary adenomas. Finally, invasive pituitary
      adenomas cells displayed lower proliferative ability than glioblastoma. Our data
      indicate that a subpopulation of stem/progenitor-like cells are present in
      pituitary adenomas, and these cells may be responsible for benign tumor
      initiation and maintenance.

PMID- 24732808
TI  - Multi-targeted therapy of cancer by niclosamide: A new application for an old
      drug.
AB  - The rapid development of new anticancer drugs that are safe and effective is a
      common goal shared by basic scientists, clinicians and patients. The current
      review discusses one such agent, namely niclosamide, which has been used in the
      clinic for the treatment of intestinal parasite infections. Recent studies
      repeatedly identified niclosamide as a potential anticancer agent by various high
      throughput screening campaigns. Niclosamide not only inhibits the Wnt/beta
      catenin, mTORC1, STAT3, NF-kappaB and Notch signaling pathways, but also targets
      mitochondria in cancer cells to induce cell cycle arrest, growth inhibition and
      apoptosis. A number of studies have established the anticancer activities of
      niclosamide in both in vitro and in vivo models. Moreover, the inhibitory effects
      of niclosamide on cancer stem cells provide further evidence for its
      consideration as a promising drug for cancer therapy. This article reviews
      various aspects of niclosamide as they relate to its efficacy against cancer and
      associated molecular mechanisms.

PMID- 24732810
TI  - The Influence of Age and Comorbidity on the Benefit of Adding Androgen
      Deprivation to Dose-escalated Radiation in Men With Intermediate-risk Prostate
      Cancer.
AB  - OBJECTIVE: Androgen deprivation therapy (ADT) can improve outcomes for men with
      intermediate-risk prostate cancer (IR-PrCa) receiving external-beam radiotherapy
      (EBRT). Older men and men with significant comorbidity may be more susceptible to
      the harms of ADT, therefore we aimed to determine whether these men benefit from
      ADT. METHODS: The adult comorbidity evaluation-27 index categorized severity of
      comorbidity in 636 men treated for IR-PrCa with dose-escalated EBRT (>75 Gy). The
      cohort was dichotomized at median age of 70. Multivariate Cox proportional hazard
      analysis evaluated the association of ADT with failure-free survival (FFS) for
      each age and comorbidity subgroup. RESULTS: A total of 48% of men were 70 years
      and above. After adjustment for tumor characteristics, the addition of ADT to
      EBRT was associated with improved FFS for both men below 70 years of age
      (adjusted hazard ratio [AHR] 0.44; 95% confidence interval [CI], 0.19-0.99;
      P=0.046) and men 70 years and above (AHR 0.23; 95% CI, 0.06-0.91; P=0.035). ADT
      improved FFS for men below 70 years who had no or mild comorbidity (AHR 0.25; 95%
      CI, 0.09-0.73; P=0.011) but not for men below 70 years who had moderate or severe
      comorbidity (AHR 1.62; 95% CI, 0.35-7.49; P=0.537). Similarly, in men 70 years
      and above, there was a trend for improved FFS with ADT in healthy men (AHR 0.10;
      95% CI, 0.01-1.08; P=0.058) but not in men with moderate to severe comorbidity
      (AHR 0.38; 95% CI, 0.06-2.56; P=0.318). CONCLUSIONS: The addition of ADT to dose
      escalated EBRT can improve outcomes for both younger and older men with IR-PrCa.
      This benefit was more pronounced in healthy men.

PMID- 24732809
TI  - The Warburg effect in tumor progression: mitochondrial oxidative metabolism as an
      anti-metastasis mechanism.
AB  - Compared to normal cells, cancer cells strongly upregulate glucose uptake and
      glycolysis to give rise to increased yield of intermediate glycolytic metabolites
      and the end product pyruvate. Moreover, glycolysis is uncoupled from the
      mitochondrial tricarboxylic acid (TCA) cycle and oxidative phosphorylation
      (OXPHOS) in cancer cells. Consequently, the majority of glycolysis-derived
      pyruvate is diverted to lactate fermentation and kept away from mitochondrial
      oxidative metabolism. This metabolic phenotype is known as the Warburg effect.
      While it has become widely accepted that the glycolytic intermediates provide
      essential anabolic support for cell proliferation and tumor growth, it remains
      largely elusive whether and how the Warburg metabolic phenotype may play a role
      in tumor progression. We hereby review the cause and consequence of the
      restrained oxidative metabolism, in particular in the context of tumor
      metastasis. Cells change or lose their extracellular matrix during the metastatic
      process. Inadequate/inappropriate matrix attachment generates reactive oxygen
      species (ROS) and causes a specific type of cell death, termed anoikis, in normal
      cells. Although anoikis is a barrier to metastasis, cancer cells have often
      acquired elevated threshold for anoikis and hence heightened metastatic
      potential. As ROS are inherent byproducts of oxidative metabolism, forced
      stimulation of glucose oxidation in cancer cells raises oxidative stress and
      restores cells' sensitivity to anoikis. Therefore, by limiting the pyruvate flux
      into mitochondrial oxidative metabolism, the Warburg effect enables cancer cells
      to avoid excess ROS generation from mitochondrial respiration and thus gain
      increased anoikis resistance and survival advantage for metastasis. Consistent
      with this notion, pro-metastatic transcription factors HIF and Snail attenuate
      oxidative metabolism, whereas tumor suppressor p53 and metastasis suppressor
      KISS1 promote mitochondrial oxidation. Collectively, these findings reveal
      mitochondrial oxidative metabolism as a critical suppressor of metastasis and
      justify metabolic therapies for potential prevention/intervention of tumor
      metastasis. 

PMID- 24732811
TI  - A Phase II Study of Concurrent Chemoradiotherapy With Paclitaxel and Cisplatin
      for Inoperable Esophageal Squamous Cell Carcinoma.
AB  - OBJECTIVES: A phase II study was performed to investigate the efficacy and the
      safety of a 3-week schedule of paclitaxel (PTX) plus cisplatin (DDP) combined
      with concurrent radiotherapy for esophageal squamous cell cancer. PATIENTS AND
      METHODS: Patients with newly diagnosed esophageal squamous cell cancer who had
      histologic proof of local-regional carcinoma of the esophagus, a Karnofsky
      performance status of 80 or greater, and normal liver, renal, and bone marrow
      functions were enrolled in the phase II trial. Chemotherapy consisted of DDP (25
      mg/m/d) for 3 days plus PTX (175 mg/m) given for 3 hours, every 3 weeks for 4
      cycles. The total dose of concurrent radiation with 68.4 Gy/44 Fx (late course
      accelerated radiotherapy) or 61.2 Gy/34 Fx (conventional radiotherapy) was given
      at the first day of chemotherapy. RESULTS: Between July 2008 and November 2011,
      76 patients were enrolled in this trial. The median age was 58 years (range, 37
      to 74 y). The stages were stage II (21 patients), stage III (27 patients), and
      stage IV (28 patients). A total of 89.5% (68/76) and 63.2% (48/76) patients
      completed >=2 cycles and all 4 cycles of chemotherapy, respectively. With the
      median follow-up of 36 months, the overall median survival time was 28.5 months
      and the progression-free survival time was 14.7 months. One- and 3-year survival
      rates were 75% and 41%, respectively. Neutropenia grade 3 and 4 occurred in 30.3%
      and 31.6% of the patients, respectively. CONCLUSIONS: Radiotherapy concurrent
      with a 3-week schedule of PTX and DDP resulted in an encouraging overall survival
      rate, but a relatively higher hematological toxicity.

PMID- 24732812
TI  - Efficacy of Low-dose and High-dose Radioactive Iodine Ablation With rhTSH in
      Korean Patients With Differentiated Thyroid Carcinoma: The First Report in
      Nonwestern Countries.
AB  - OBJECTIVE: The aim of this study was to confirm the equivalent efficacy of
      recombinant human TSH (rhTSH) and thyroid hormone withdrawal (THW) as used in the
      preparation for low-dose and high-dose radioactive iodine (RAI) ablation in
      Korean patients with differentiated thyroid carcinoma. SUBJECTS AND METHODS: This
      retrospective study was designed to compare the efficacy of rhTSH and THW when
      used before ablation with low-dose (30 mCi) and high-dose (100 mCi) RAI,
      respectively. The study group included 570 patients with DTC with tumors staged
      T1 to T3, N0 to N1, and M0. Before RAI ablation, 190 patients used rhTSH and 380
      patients matched by age, sex, T-stage, and N-stage used THW. The success of
      ablation was evaluated in each group based on 4 criteria: (1) stimulated
      thyroglobulin (sTg) <2 ng/mL, (2) sTg<2 ng/mL and negative diagnostic whole-body
      scan (DxWBS), (3) sTg<1 ng/mL, and (4) sTg<1 ng/mL and negative DxWBS. RESULTS:
      When both sTg<2 ng/mL and negative DxWBS were selected as criteria for success in
      patients treated with low-dose RAI, the success rates were 80.5% and 77.0% with
      rhTSH and THW, respectively (95% confidence interval, 5.9-12.8). Using both sTg<1
      ng/mL and negative DxWBS as criteria, success rates were 78.2% and 71.8% with
      rhTSH and THW, respectively (95% confidence interval, 3.6-16.2). Using any
      criteria for success, low-dose RAI ablation with rhTSH was as effective as THW.
      Similar results were found for high-dose RAI ablation in patients using either
      rhTSH or THW. CONCLUSIONS: Low-dose and high-dose RAI ablation were equally
      effective using either rhTSH or THW before ablation in Korean patients with DTC,
      respectively.

PMID- 24732813
TI  - Kenya AIDS Indicator Survey 2012.

PMID- 24732814
TI  - Tuberculosis and HIV at the national level in Kenya: results from the Second
      Kenya AIDS Indicator Survey.
AB  - BACKGROUND: Co-morbidity with tuberculosis and HIV is a common cause of mortality
      in sub-Saharan Africa. In the second Kenya AIDS Indicator Survey, we collected
      data on knowledge and experience of HIV and tuberculosis, as well as on access to
      and coverage of relevant treatment services and antiretroviral therapy (ART) in
      Kenya. METHODS: A national, population-based household survey was conducted from
      October 2012 to February 2013. Information was collected through household
      questionnaires, and blood samples were taken for HIV, CD4 cell counts, and HIV
      viral load testing at a central laboratory. RESULTS: Overall, 13,720 persons aged
      15-64 years participated; 96.7% [95% confidence interval (CI): 96.3 to 97.1] had
      heard of tuberculosis, of whom 2.0% (95% CI: 1.7 to 2.2) reported having prior
      tuberculosis. Among those with laboratory-confirmed HIV infection, 11.6% (95% CI:
      8.9 to 14.3) reported prior tuberculosis. The prevalence of laboratory-confirmed
      HIV infection in persons reporting prior tuberculosis was 33.2% (95% CI: 26.2 to
      40.2) compared to 5.1% (95% CI: 4.5 to 5.8) in persons without prior
      tuberculosis. Among those in care, coverage of ART for treatment-eligible persons
      was 100% for those with prior tuberculosis and 88.6% (95% CI: 81.6 to 95.7) for
      those without. Among all HIV-infected persons, ART coverage among treatment
      eligible persons was 86.9% (95% CI: 74.2 to 99.5) for persons with prior
      tuberculosis and 58.3% (95% CI: 47.6 to 69.0) for those without. CONCLUSIONS:
      Morbidity from tuberculosis and HIV remain major health challenges in Kenya.
      Tuberculosis is an important entry point for HIV diagnosis and treatment. Lack of
      knowledge of HIV serostatus is an obstacle to access to HIV services and timely
      ART for prevention of HIV transmission and HIV-associated disease, including
      tuberculosis.

PMID- 24732815
TI  - Antiretroviral treatment scale-up among persons living with HIV in Kenya: results
      from a nationally representative survey.
AB  - BACKGROUND: In 2007, 29% of HIV-infected Kenyans in need of antiretroviral
      therapy (ART), based on an immunologic criterion of CD4 <=350 cells per
      microliter, were receiving ART. Since then, substantial treatment scale-up has
      occurred in the country. We analyzed data from the second Kenya AIDS Indicator
      Survey (KAIS 2012) to assess progress of treatment scale-up in Kenya. METHODS:
      KAIS 2012 was a nationally representative survey of persons aged 18 months to 64
      years that collected information on HIV status, care, and treatment. ART
      eligibility was defined based on 2 standards: (1) 2011 Kenya eligibility criteria
      for ART initiation: CD4 <=350 cells per microliter or co-infection with active
      tuberculosis and (2) 2013 World Health Organization (WHO) eligibility criteria
      for ART initiation: CD4 <=500 cells per microliter, co-infection with active
      tuberculosis, currently pregnant or breastfeeding, and infected partners in
      serodiscordant relationships. Blood specimens were tested for HIV antibodies and
      HIV-positive specimens tested for CD4 cell counts. RESULTS: Among 13,720 adults
      and adolescents aged 15-64 years, 11,626 provided a blood sample, and 648 were
      HIV infected. Overall, 58.8% [95% confidence interval (CI): 52.0 to 65.5) were
      eligible for treatment using the 2011 Kenya eligibility criteria and 77.4% (95%
      CI: 72.4 to 82.4) using the 2013 WHO eligibility criteria. Coverage of ART was
      60.5% (95% CI: 50.8 to 70.2) using the 2011 Kenya eligibility criteria and 45.9%
      (95% CI: 37.7 to 54.2) using the 2013 WHO eligibility criteria. CONCLUSIONS: ART
      coverage has increased from 29% in 2007 to 61% in 2012. If Kenya adopts the 2013
      WHO guidelines for ART initiation, need for ART increases by an additional 19
      percentage points and current coverage decreases by an additional 15 percentage
      points, representing an additional 214,000 persons who will need to be reached.

PMID- 24732816
TI  - Using information and communications technology in a national population-based
      survey: the Kenya AIDS Indicator Survey 2012.
AB  - BACKGROUND: With improvements in technology, electronic data capture (EDC) for
      large surveys is feasible. EDC offers benefits over traditional paper-based data
      collection, including more accurate data, greater completeness of data, and
      decreased data cleaning burden. METHODS: The second Kenya AIDS Indicator Survey
      (KAIS 2012) was a population-based survey of persons aged 18 months to 64 years.
      A software application was designed to capture the interview, specimen
      collection, and home-based testing and counseling data. The application included:
      interview translations for local languages; options for single, multiple, and
      fill-in responses; and automated participant eligibility determination. Data
      quality checks were programmed to automate skip patterns and prohibit outlier
      responses. A data sharing architecture was developed to transmit the data in real
      time from the field to a central server over a virtual private network. RESULTS:
      KAIS 2012 was conducted between October 2012 and February 2013. Overall, 68,202
      records for the interviews, specimen collection, and home-based testing and
      counseling were entered into the application. Challenges arose during
      implementation, including poor connectivity and a systems malfunction that
      created duplicate records, which prevented timely data transmission to the
      central server. Data cleaning was minimal given the data quality control
      measures. CONCLUSIONS: KAIS 2012 demonstrated the feasibility of using EDC in a
      population-based survey. The benefits of EDC were apparent in data quality and
      minimal time needed for data cleaning. Several important lessons were learned,
      such as the time and monetary investment required before survey implementation,
      the importance of continuous application testing, and contingency plans for data
      transmission due to connectivity challenges.

PMID- 24732817
TI  - Kenya AIDS Indicator Surveys 2007 and 2012: implications for public health
      policies for HIV prevention and treatment.
AB  - AIDS Indicator Surveys are standardized surveillance tools used by countries with
      generalized HIV epidemics to provide, in a timely fashion, indicators for
      effective monitoring of HIV. Such data should guide responses to the HIV
      epidemic, meet program reporting requirements, and ensure comparability of
      findings across countries and over time. Kenya has conducted 2 AIDS Indicator
      Surveys, in 2007 (KAIS 2007) and 2012-2013 (KAIS 2012). These nationally
      representative surveys have provided essential epidemiologic, sociodemographic,
      behavioral, and biologic data on HIV and related indicators to evaluate the
      national HIV response and inform policies for prevention and treatment of the
      disease. We present a summary of findings from KAIS 2007 and KAIS 2012 and the
      impact that these data have had on changing HIV policies and practice.

PMID- 24732818
TI  - The status of HIV testing and counseling in Kenya: results from a nationally
      representative population-based survey.
AB  - BACKGROUND: HIV testing and counseling (HTC) is essential for successful HIV
      prevention and treatment programs. The national target for HTC is 80% of the
      adult population in Kenya. Population-based data to measure progress towards this
      HTC target are needed to assess the country's changing needs for HIV prevention
      and treatment. METHODS: In 2012-2013, we conducted a national HIV survey among
      Kenyans aged 18 months to 64 years. Respondents aged 15-64 years were
      administered a questionnaire that collected information on demographics, HIV
      testing behavior, and self-reported HIV status. Blood samples were collected for
      HIV testing in a central laboratory. Participants were offered home-based testing
      and counseling to learn their HIV status in the home and point-of-care CD4
      testing if they tested HIV-positive. RESULTS: Of 13,720 adults who were
      interviewed, 71.6% [95% confidence interval (CI): 70.2 to 73.1] had been tested
      for HIV. Among those, 56.1% (95% CI: 52.8 to 59.4) had been tested in the past
      year, 69.4% (95% CI: 68.0 to 70.8) had been tested more than once, and 37.2% (95%
      CI: 35.7 to 38.8) had been tested with a partner. Fifty-three percent (95% CI:
      47.6 to 58.7) of HIV-infected persons were unaware of their infection. Overall
      9874 (72.0%) of participants accepted home-based HIV testing and counseling; 4.1%
      (95% CI: 3.3 to 4.9) tested HIV-positive, and of those, 42.5% (95% CI 31.4 to
      53.6) were in need of immediate treatment for their HIV infection but not
      receiving it. CONCLUSIONS: HIV testing rates have nearly reached the national
      target for HTC in Kenya. However, knowledge of HIV status among HIV-infected
      persons remains low. HTC needs to be expanded to reach more men and couples, and
      strategies are needed to increase repeat testing for persons at risk for HIV
      infection.

PMID- 24732819
TI  - The Kenya AIDS Indicator Survey 2012: rationale, methods, description of
      participants, and response rates.
AB  - BACKGROUND: Cross-sectional population-based surveys are essential surveillance
      tools for tracking changes in HIV epidemics. In 2007, Kenya implemented the first
      AIDS Indicator Survey [Kenya AIDS Indicator Survey (KAIS) 2007)], a nationally
      representative, population-based survey that collected demographic and behavioral
      data and blood specimens from individuals aged 15-64 years. Kenya's second AIDS
      Indicator Survey (KAIS 2012) was conducted to monitor changes in the epidemic,
      evaluate HIV prevention, care, and treatment initiatives, and plan for an
      efficient and effective response to the HIV epidemic. METHODS: KAIS 2012 was a
      cross-sectional 2-stage cluster sampling design, household-based HIV serologic
      survey that collected information on households as well as demographic and
      behavioral data from Kenyans aged 18 months to 64 years. Participants also
      provided blood samples for HIV serology and other related tests at the National
      HIV Reference Laboratory. RESULTS: Among 9300 households sampled, 9189 (98.8%)
      were eligible for the survey. Of the eligible households, 8035 (87.4%) completed
      household-level questionnaires. Of 16,383 eligible individuals aged 15-64 years
      and emancipated minors aged less than 15 years in these households, 13,720
      (83.7%) completed interviews; 11,626 (84.7%) of the interviewees provided a blood
      specimen. Of 6302 eligible children aged 18 months to 14 years, 4340 (68.9%)
      provided a blood specimen. Of the 2094 eligible children aged 10-14 years, 1661
      (79.3%) completed interviews. CONCLUSIONS: KAIS 2012 provided representative data
      to inform a strategic response to the HIV epidemic in the country.

PMID- 24732820
TI  - Status of voluntary medical male circumcision in Kenya: findings from 2
      nationally representative surveys in Kenya, 2007 and 2012.
AB  - BACKGROUND: The Kenyan Ministry of Health initiated a voluntary medical male
      circumcision (VMMC) program in 2008. We used data from 2 nationally
      representative surveys to estimate trends in the number, demographic
      characteristics, and sexual behaviors of recently circumcised and uncircumcised
      HIV-uninfected men in Kenya. METHODS: We compared the proportion of circumcised
      men between the first and second Kenya AIDS Indicator Survey (KAIS 2007 and KAIS
      2012) to assess the progress of Kenya's VMMC program. We calculated the number of
      uncircumcised HIV-uninfected men. We conducted descriptive analyses and used
      multivariable methods to identify the variables independently associated with HIV
      uninfected uncircumcised men aged 15-64 years in the VMMC priority region of
      Nyanza. RESULTS: The proportion of men who reported being circumcised increased
      significantly from 85.0% in 2007 to 91.2% in 2012. The proportions of circumcised
      men increased in all regions, with the highest increases of 18.1 and 9.0
      percentage points in the VMMC priority regions of Nyanza and Nairobi,
      respectively. Half (52.5%) of HIV-uninfected and uncircumcised men had never been
      married, and 84.6% were not using condoms at all times with their last sexual
      partner. CONCLUSIONS: VMMC prevalence has increased across Kenya demonstrating
      the success of the national program. Despite this accomplishment, the Nyanza
      region remains below the target to circumcise 80% of all eligible men aged 15-49
      years between 2009 and 2013. As new cohorts of young men enter into adolescence,
      consistent focus is needed. To ensure sustainability of the VMMC program,
      financial resources and coordinated planning must continue.

PMID- 24732821
TI  - Populations at increased risk for HIV infection in Kenya: results from a national
      population-based household survey, 2012.
AB  - BACKGROUND: Populations with higher risks for HIV exposure contribute to the HIV
      epidemic in Kenya. We present data from the second Kenya AIDS Indicator Survey to
      estimate the size and HIV prevalence of populations with high-risk
      characteristics. METHODS: The Kenya AIDS Indicator Survey 2012 was a national
      survey of Kenyans aged 18 months to 64 years which linked demographic and
      behavioral information with HIV results. Data were weighted to account for
      sampling probability. This analysis was restricted to adults aged 18 years and
      older. RESULTS: Of 5088 men and 6745 women, 0.1% [95% confidence interval (CI):
      0.03 to 0.14] were persons who inject drugs (PWID). Among men, 0.6% (CI: 0.3 to
      0.8) had ever had sex with other men, and 3.1% (CI: 2.4 to 3.7) were males who
      had ever engaged in transactional sex work (MTSW). Among women, 1.9% (CI: 1.3 to
      2.5) had ever had anal sex, and 4.1% (CI: 3.5 to 4.8) were women who had ever
      engaged in transactional sex work (FTSW). Among men, 17.6% (CI: 15.7 to 19.6) had
      been male clients of transactional sex workers (TSW). HIV prevalence was 0% among
      men who have sex with men, 6.3% (CI: 0 to 18.1) among persons who injected drugs,
      7.1% (CI: 4.8 to 9.4) among male clients of TSW, 7.6% (CI: 1.8 to 13.4) among
      MTSW, 12.1% (CI: 7.1 to 17.1) among FTSW, and 12.1% (CI: 5.0 to 19.2) among
      females who ever had engaged in anal sex. CONCLUSIONS: Population-based data on
      high-risk populations can be used to set realistic targets for HIV prevention,
      care, and treatment for these groups. These data should inform priorities for
      high-risk populations in the upcoming Kenyan strategic plan on HIV/AIDS.

PMID- 24732822
TI  - Mother-to-child transmission of HIV in Kenya: results from a nationally
      representative study.
AB  - BACKGROUND: Kenya has an estimated 13,000 new infant HIV infections that occur
      annually. We measured the burden of HIV infection among women of childbearing age
      and assessed access to and coverage of key prevention of mother-to-child
      transmission interventions. METHODS: The second Kenya AIDS Indicator Survey was a
      nationally representative 2-stage cluster sample of households. We analyzed data
      from women aged 15-54 years who had delivered a newborn within the preceding 5
      years and from whom we obtained samples for HIV testing. RESULTS: Of 3310 women
      who had >=1 live birth in the preceding 5 years, 2862 (86.5%) consented to HIV
      testing in the survey, and 171 (6.1%) were found to be infected. Ninety-five
      percent received prenatal care, 93.1% were screened for HIV during prenatal care,
      and of those screened, 97.8% received their test results. Seventy-six women were
      known to be infected in their last pregnancy. Of these, 54 (72.3%) received
      antepartum antiretroviral prophylaxis, and 51 (69.1%) received intrapartum
      prophylaxis; 56 (75.3%) reported their newborns received postpartum prophylaxis.
      Of the 76 children born to these mothers, 63 (82.5%) were tested for HIV at the
      first immunization visit or thereafter, and 8 (15.1%) were HIV infected.
      CONCLUSIONS: We found a substantial burden of HIV in Kenyan women of childbearing
      age and a cumulative 5-year mother-to-child transmission rate of 15%. Although
      screening has improved over the past 5 years, fewer than three-quarters of
      infected pregnant women are receiving antiretroviral prophylaxis. Universal
      antiretroviral therapy for HIV-infected pregnant women will be essential in
      achieving Kenyan's target to eliminate mother-to-child transmission to <5% by
      2015.

PMID- 24732823
TI  - Burden of HIV infection among children aged 18 months to 14 years in Kenya:
      results from a nationally representative population-based cross-sectional survey.
AB  - BACKGROUND: In Kenya, mathematical models estimate that there are approximately
      220,000 children aged less than 15 years infected with HIV. We analyzed data from
      the second Kenya AIDS Indicator Survey (KAIS 2012) to estimate the prevalence of
      HIV infection among children aged 18 months to 14 years. METHODS: KAIS 2012 was a
      nationally representative 2-stage cluster sample household survey. We studied
      children aged 18 months to 14 years whose parents or guardians answered questions
      pertaining to their children by interview. Blood specimens were collected for HIV
      serology and viral load measurement. RESULTS: We identified 5162 children who
      were eligible for the study. Blood was obtained for 3681 (71.3%) children. Among
      child participants, 16.4% had been tested for HIV infection in the past, and
      among children with parents or guardians who self-reported HIV-positive status,
      52.9% had been tested for HIV infection. Twenty-eight (0.9%) children tested HIV
      positive in the survey. Of these, 11 had been previously diagnosed with HIV
      infection before the survey. All 11 children were in HIV care and receiving
      cotrimoxazole; 8 were on antiretorivral therapy (ART). Among those on ART, 4 were
      virologically suppressed. CONCLUSIONS: HIV causes a substantial burden of disease
      in the Kenyan pediatric population. Although most children who had been diagnosed
      with HIV before the survey were engaged in care and treatment, they represented
      less than half of HIV-infected children identified in the survey. Future efforts
      should focus on identifying infected children and getting them into care and on
      suppressive ART as early as possible.

PMID- 24732824
TI  - Orphans and vulnerable children in Kenya: results from a nationally
      representative population-based survey.
AB  - BACKGROUND: In Kenya, it is estimated that there are approximately 3.6 million
      children aged <18 years who have been orphaned or who are vulnerable. We examined
      the data from the second Kenya AIDS Indicator Survey (KAIS 2012) to determine the
      number and profile of orphans and vulnerable children (OVC) in Kenya who were
      aged <18 years. METHODS: KAIS 2012 was a nationally representative, population
      based household survey. We analyzed the data for all the children from birth to
      age 17 years who resided in an eligible household so as to determine whether
      their parents were alive or had been very ill to define their OVC status.
      RESULTS: We estimated that there were 2.6 million OVC in Kenya in 2012, of whom
      1.8 million were orphans and 750,000 were vulnerable. Among orphans, 15% were
      double orphans. Over one-third of all the OVC were aged between 10 and 14 years.
      Households with >=1 OVC (12% of all households) were usually in the lowest 2
      wealth quintiles, and 22% of OVC households had experienced moderate or severe
      hunger. Receipt of OVC support services was low for medical (3.7%), psychological
      (4.1%), social (1.3%), and material support (6.2%); educational support was
      slightly more common (11.5%). Orphanhood among children aged <15 years increased
      from 1993 to 2003 (P < 0.01) but declined from 2003 to 2012 (P < 0.01).
      CONCLUSIONS: The 2.6 million OVC constitute a significant proportion of Kenya's
      population aged <18 years. Special attention should be paid to OVC to prevent
      further vulnerability and ensure their well-being and development as they
      transition into adulthood.

PMID- 24732827
TI  - Volatile anaesthesia during cardiopulmonary bypass.
AB  - Since its inception, administering and ensuring anaesthesia during
      cardiopulmonary bypass has been challenging. Partly because of the difficulty of
      administering volatile agents during cardiopulmonary bypass, total intravenous
      anaesthesia has been a popular technique used by cardiac anaesthetists in the
      last two decades. However, the possibility that volatile agents reduce mortality
      and the incidence of myocardial infarction by preconditioning the myocardium has
      stimulated a resurgence of interest in their use for cardiac anaesthesia. The aim
      of this review is to provide an overview of the administration of volatile
      anaesthetic agents during cardiopulmonary bypass for the maintenance of
      anaesthesia and to address some of the practical issues that are involved in
      doing so. 

PMID- 24732826
TI  - High-performance fluorescence molecular tomography through shape-based
      reconstruction using spherical harmonics parameterization.
AB  - Fluorescence molecular tomography in the near-infrared region is becoming a
      powerful modality for mapping the three-dimensional quantitative distributions of
      fluorochromes in live small animals. However, wider application of fluorescence
      molecular tomography still requires more accurate and stable reconstruction
      tools. We propose a shape-based reconstruction method that uses spherical
      harmonics parameterization, where fluorophores are assumed to be distributed as
      piecewise constants inside disjointed subdomains and the remaining background.
      The inverse problem is then formulated as a constrained nonlinear least-squares
      problem with respect to shape parameters, which decreases ill-posedness because
      of the significantly reduced number of unknowns. Since different shape parameters
      contribute differently to the boundary measurements, a two-step and modified
      block coordinate descent optimization algorithm is introduced to stabilize the
      reconstruction. We first evaluated our method using numerical simulations under
      various conditions for the noise level and fluorescent background; it showed
      significant superiority over conventional voxel-based methods in terms of the
      spatial resolution, reconstruction accuracy with regard to the morphology and
      intensity, and robustness against the initial estimated distribution. In our
      phantom experiment, our method again showed better spatial resolution and more
      accurate intensity reconstruction. Finally, the results of an in vivo experiment
      demonstrated its applicability to the imaging of mice. 

PMID- 24732825
TI  - Engagement in HIV care among Kenyan adults and adolescents: results from a
      national population-based survey.
AB  - BACKGROUND: Increasing access to care and treatment for HIV-infected persons is a
      goal in Kenya's response to the HIV epidemic. Using data from the second Kenya
      AIDS Indicator Survey (KAIS 2012), we describe coverage of services received
      among adults and adolescents who were enrolled in HIV care. METHODS: KAIS 2012
      was a population-based survey that collected information from persons aged 15-64
      years that included self-reported HIV status, and for persons reporting HIV
      infection, use of HIV care and antiretroviral therapy (ART). Blood specimens were
      collected and tested for HIV. HIV-positive specimens were tested for CD4 counts
      and viral load. RESULTS: Among 363 persons who reported HIV infection, 93.4% [95%
      confidence interval (CI): 87.2 to 99.6] had ever received HIV care. Among those
      receiving HIV care, 96.3% (95% CI: 94.1 to 98.4) were using cotrimoxazole
      prophylaxis, and 74.6% (95% CI: 69.0 to 80.2) were receiving ART. A lower
      proportion of persons in care and not on ART reported using cotrimoxazole (89.5%,
      95% CI: 82.5 to 96.5 compared with 98.6%, 95% CI: 97.1 to 100) and had a CD4
      count measurement done (72.9%, 95% CI: 64.0 to 81.9 compared with 90.0%, 95% CI:
      82.8 to 97.3) than persons in care and on ART, respectively. Among persons in
      care and not on ART, 23.2% (95% CI: 6.8 to 39.7) had CD4 counts <=350 cells per
      microliter. Viral suppression was observed in 75.3% (95% CI: 68.7 to 81.9) of
      persons on ART. CONCLUSIONS: Linkage and retention in care are high among persons
      with known HIV infection. However, improvements in care for the pre-ART
      population are needed. Viral suppression rates were comparable to developed
      settings.

PMID- 24732828
TI  - Incorporating biopsychosocial characteristics into personalized healthcare: a
      clinical approach.

PMID- 24732830
TI  - Tubes lead the way.

PMID- 24732829
TI  - High resolution systematic digital histological quantification of cardiac
      fibrosis and adipose tissue in phospholamban p.Arg14del mutation associated
      cardiomyopathy.
AB  - Myocardial fibrosis can lead to heart failure and act as a substrate for cardiac
      arrhythmias. In dilated cardiomyopathy diffuse interstitial reactive fibrosis can
      be observed, whereas arrhythmogenic cardiomyopathy is characterized by fibrofatty
      replacement in predominantly the right ventricle. The p.Arg14del mutation in the
      phospholamban (PLN) gene has been associated with dilated cardiomyopathy and
      recently also with arrhythmogenic cardiomyopathy. Aim of the present study is to
      determine the exact pattern of fibrosis and fatty replacement in PLN p.Arg14del
      mutation positive patients, with a novel method for high resolution systematic
      digital histological quantification of fibrosis and fatty tissue in cardiac
      tissue. Transversal mid-ventricular slices (n = 8) from whole hearts were
      collected from patients with the PLN p.Arg14del mutation (age 48+/-16 years; 4
      (50%) male). An in-house developed open source MATLAB script was used for digital
      analysis of Masson's trichrome stained slides
      (http://sourceforge.net/projects/fibroquant/). Slides were divided into
      trabecular, inner and outer compact myocardium. Per region the percentage of
      connective tissue, cardiomyocytes and fatty tissue was quantified. In PLN
      p.Arg14del mutation associated cardiomyopathy, myocardial fibrosis is
      predominantly present in the left posterolateral wall and to a lesser extent in
      the right ventricular wall, whereas fatty changes are more pronounced in the
      right ventricular wall. No difference in distribution pattern of fibrosis and
      adipocytes was observed between patients with a clinical predominantly dilated
      and arrhythmogenic cardiomyopathy phenotype. In the future, this novel method for
      quantifying fibrosis and fatty tissue can be used to assess cardiac fibrosis and
      fatty tissue in animal models and a broad range of human cardiomyopathies. 

PMID- 24732831
TI  - Biomechanical evaluation of a low-profile, anchored cervical interbody spacer
      device at the index level or adjacent to plated fusion.
AB  - STUDY DESIGN: In vitro biomechanical study. OBJECTIVE: To test the hypotheses:
      (1) an anchored spacer device would decrease motion similarly to a plate-spacer
      construct, and (2) the anchored spacer would achieve a similar reduction in
      motion when placed adjacent to a previously fused segment. SUMMARY OF BACKGROUND
      DATA: An anchored spacer device has been shown to perform similar to the plate
      spacer construct in previous biomechanical evaluation. The prevalence of adjacent
      segment disease after fusion is well established in the literature.There is
      currently no evidence supporting the use of an anchored interbody spacer device
      adjacent to a previous fusion. METHODS: Eight human cervical spines (age: 45.1 +/
      13.1 yr) were tested in moment control (+/-1.5 Nm) in flexion-extension, lateral
      bending, and axial rotation without preload. Flexion-extension was then retested
      under 150-N preload. Spines were tested intact and after anterior cervical
      discectomy and fusion (ACDF) at C4-C5 and C6-C7 with either a plate-spacer or
      anchored spacer construct (randomized). The specimens were tested finally with an
      ACDF at the floating C5-C6 segment using the anchored spacer device adjacent to
      the previous fusions. RESULTS: Both the plate-spacer and anchored spacer
      significantly reduced motion from the intact spine in flexion-extension, lateral
      bending, and axial rotation (P < 0.005). There was no statistically significant
      difference between the 2 fusion constructs in their abilities to reduce motions
      (P = 1.0). ACDF using the anchored spacer at the floating C5-C6 level (in between
      the plate-spacer and anchored spacer constructs) resulted in significant motion
      reductions in all modes of testing (P < 0.05). These motion reductions did not
      significantly differ from those of a single-level anchored-spacer construct or a
      single-level plated ACDF. CONCLUSION: The anchored spacer provided significant
      motion reductions, similar to a plated ACDF, when used as a single-level fusion
      construct or placed adjacent to a previously plated segment. LEVEL OF EVIDENCE:
      N/A.

PMID- 24732832
TI  - Wound complications of vertical expandable prosthetic titanium rib incisions.
AB  - STUDY DESIGN: Multicenter retrospective review. OBJECTIVE: To compare the
      incidence of infection between vertical expandable prosthetic titanium rib
      (VEPTR) incision locations and determine if the infection risk increases in
      relation to presence of previous incisions and/or increased number of times
      incisions are opened. SUMMARY OF BACKGROUND DATA: Patients undergoing treatment
      for chest and spine deformity with VEPTR require multiple incisions that are
      opened repeatedly during expansion procedures. METHODS: A prospective database (7
      sites) and institutional database (2 sites), were queried to identify their 20
      most recent patients with VEPTR with a minimum of 4 expansions for inclusion. A
      total of 103 patients were identified. Clinical and operative reports were
      reviewed to determine incision locations, number, and infection complications.
      RESULTS: Twenty-five of 103 patients (24%) developed an infection during
      treatment. Six had multiple infections (range, 2-4), providing a total of 34
      infection events. Patients averaged 6.4 expansion procedures and 13 total
      incisions. Infection rate at each incision site was not significantly different,
      in the range from 1% to 5%: paramedian (6 infections/23 patients with total 185
      incisions, 3%), proximal midline (12/39; 224, 5%), thoracotomy (6/61; 455, 1%),
      iliac (5/37; 143, 4%), and distal midline (5/58; 148, 3%). Infection events
      occurred after an average of 3 times a particular incision was opened (95%
      confidence interval: 2.2-3.8). There was a trend toward higher infection rate
      with increased number of times a particular incision was opened. There was no
      increased infection rate in patients with surgical incisions prior to VEPTR (26%;
      6/23) compared with patients not having prior incisions (24%; 19/80). CONCLUSION:
      The incidence of infection in patients with 4 or more VEPTR lengthenings was 24%
      and did not differ across the various incision locations. Presence of prior
      surgical incisions was not a risk factor for infection. Surgeons should use the
      most appropriate incision in relation to their patient's pathology when using
      VEPTR while remaining vigilant for infection. LEVEL OF EVIDENCE: 3.

PMID- 24732834
TI  - Biomechanical effects of cage positions and facet fixation on initial stability
      of the anterior lumbar interbody fusion motion segment.
AB  - STUDY DESIGN: An in vitro biomechanical study using porcine lumbar segments as
      specimens. OBJECTIVE: To evaluate the effects of interbody cage support and
      endplate strength on the stability of instrumented segments. SUMMARY OF
      BACKGROUND DATA: The anterior lumbar interbody fusion (ALIF) cage is widely used
      to restore disc height and support the anterior column. Transpedicle or posterior
      spinal fusion or facet screw fixation (FSF) can improve the stability of the
      vertebra-instrumented segments. The cage position can affect the anterior support
      and initial stability of the ALIF region, but there is no consistent data on its
      biomechanical effects on ALIF and ALIF/FSF segments. METHODS: Nine variations of
      3 instrumentation modes (intact, ALIF, ALIF/FSF) and 3 cage positions (type I,
      anterolateral; type II, mediolateral; and type III, posteromedial) are tested
      under 5 lumbar motions. The range of motion and axial displacement are used as
      comparison indices for the different variations. RESULTS: The cage placement
      serves as support for the intervertebral loads while the posterior fixation
      behaves as lever to further enhance the anterior support. At the endplate-cage
      interfaces, the endplate strength directly affects the cage subsidence. Type III
      exhibits higher stability for standing due to the greater strength of the
      endplate in the posterior region. Otherwise, type I consistently has higher
      stability for all other types of motion. CONCLUSION: The initial stability of the
      ALIF region is affected by the moment arm and the mechanical strength of the
      engaged endplates. Type I has greater moment arm and provides more efficient
      support to the instrumented segments. Endplate strength provides an ability to
      withstand lumbar loads and suppress the cage subsidence. Bone quality at the
      endplate-cage interfaces must therefore be cautiously evaluated preoperatively.
      LEVEL OF EVIDENCE: N/A.

PMID- 24732833
TI  - Radiation exposure to the surgeon and the patient during posterior lumbar spinal
      instrumentation: a prospective randomized comparison of navigated versus non
      navigated freehand techniques.
AB  - STUDY DESIGN: A prospective randomized study. OBJECTIVE: To compare occupational
      radiation exposure to the surgeon, as well as the patient, during posterior
      lumbar spine instrumentation in 10 navigated cases (navigated) versus 11 cases
      using the freehand technique (non-navigated). SUMMARY OF BACKGROUND DATA: The use
      of navigation increases the accuracy of posterior lumbar instrumentation.A
      further speculated benefit of navigation is the reduction of radiation exposure
      of the surgeon. However, this has so far not been evaluated in such comparative
      manner. METHODS: Radiation exposure to the surgeon was measured by digital
      dosimeters placed at the level of the eye, chest, and dominant forearm. Radiation
      exposure was measured from the time of positioning of the patient to the end of
      the procedure both for navigated (intraoperative 3-dimensional [3D] fluoroscopy
      based) and non-navigated (2-dimensional fluoroscopy-guided) freehand posterior
      lumbar spine instrumentations. A 3D fluoroscopic scan was routinely performed at
      the end of the procedure for all patients. RESULTS: Patients were distributed
      evenly in the 2 groups in terms of sex, age, body mass index, and the number of
      operated levels. The accumulated radiation dose for the surgeon was significantly
      higher in the non-navigated group; up to 9.96 times. The radiation dose for the
      patient was higher with the freehand technique, 1884.8 cGy.cm (non-navigated)
      versus 887 cGy.cm (navigated), without reaching a statistically significant
      level. CONCLUSION: Radiation exposure to the surgeon during pedicle screw
      placement with the freehand technique is up to 9.96 times greater than with the
      use of navigation. In the latter group, the only radiation exposure comes from
      the preoperative-level control and positioning of the 3D C-arm before 3D
      fluoroscopic acquisition. Furthermore, neuronavigation also reduces the
      cumulative dose for the patient. LEVEL OF EVIDENCE: 2.

PMID- 24732835
TI  - C2 nerve root on magnetic resonance imaging of occipital neuralgia.
AB  - STUDY DESIGN: Review and grade the morphology of the C1-C2 neural foramina, from
      the MR images of patients who underwent C1-C2 spinal surgery, and determine the
      relationship with ON. OBJECTIVE: To evaluate the feasibility of MRI for C1-C2
      neural foramen evaluation with a new grading system and to correlate the C1-C2
      neural foramen grade with ON. SUMMARY OF BACKGROUND DATA: There have been no MRI
      studies of patients with and without ON in relation to C2 nerve root ganglion
      findings. METHODS: Among the registry of 124 patients who underwent C1-C2 spinal
      surgery between July 2004 and May 2012 in Seoul National University Bundang
      Hospital, we enrolled 101 patients who had information about ON and a relevant
      preoperative cervical spine MR image. A total of 202 neural foramina were
      evaluated with our new C1-C2 neural foramen grading system (grade, 0-3) using
      consensus reading by 2 experienced radiologists who were blinded to the clinical
      information. The relationship between the C1-C2 grading system and ON was
      assessed using a chi test and Fisher exact test. Inter- and intraobserver
      reliability agreement was assessed using the kappa statistic. RESULTS: All C1-C2
      neural foramina were delineated on T2 parasagittal images. Among 202 C1-C2 neural
      foramina, grade zero was found in 49 foramina (24.3%), grade 1 in 95 (47.0%),
      grade 2 in 30 (14.9%), and grade 3 in 28 (13.9%). Grade 1 stenosis was most
      frequently noted. The grade 2 group had the most frequent prevalence of ON
      (43.3%), followed by grade 3 (35.7%), grade zero (30.6%), and grade 1 (29.5%).
      However, the relationship between the grade and ON was not statistically
      significant. Inter- and intraobserver agreements were substantially high.
      CONCLUSION: C1-C2 neural foramina can be depicted on MR image. However, the
      relationship between the new grading system for C1-C2 neural foramina and ON was
      not statistically significant. LEVEL OF EVIDENCE: 4.

PMID- 24732836
TI  - Upregulation of tumor necrosis factor alpha and ADAMTS-5, but not ADAMTS-4, in
      human intervertebral cartilage endplate with modic changes.
AB  - STUDY DESIGN: This study investigated the expression of 2 types of ADAMTS in
      human intervertebral cartilage endplate (CEP) and related mechanisms concerning
      tumor necrosis factor alpha (TNF-alpha)-induced nuclear factor kappaB signaling
      pathway. OBJECTIVE: To determine which type of ADAMTS is more strongly expressed
      and the role of TNF-alpha in CEP. SUMMARY OF BACKGROUND DATA: ADAMTS-4 and ADAMTS
      5 were proven to be essential in the degeneration of articular cartilage and
      intervertebral disc. CEP is an important structure adjacent to the disc. However,
      the activities of ADAMTS in CEP are unclear. METHODS: CEPs were obtained from
      subjects after spinal surgery and categorized as members of either the Modic
      change group or the control group. Sections of these tissues were stained with
      hematoxylin-eosin, safranin O, and immunohistochemistry procedures for ADAMTS-4,
      ADAMTS-5, and TNF-alpha. Transcriptional levels of aggrecan, type I collagen,
      type II collagen, type X collagen, ADAMTS-4, ADAMTS-5, and TNF-alpha were
      investigated by quantitative real-time polymerase chain reaction. In addition,
      the effect of TNF-alpha on ADAMTS-5 and its potential mechanisms are investigated
      in cultured bovine endplate chondrocytes in vitro. RESULTS: Our data demonstrated
      that the degenerative changes associated with the expression of extracellular
      matrix proteins were correlated with increased levels of ADAMTS-5, but not ADAMTS
      4, in the CEP of patients with Modic changes. The expression levels of TNF-alpha
      in the Modic change group were significantly increased, which was correlated with
      the enhanced expression of ADAMTS-5. Additional in vitro investigation confirmed
      that TNF-alpha could upregulate the expression of ADAMTS-5 by activating nuclear
      factor kappaB pathway in cultured bovine endplate chondrocytes. CONCLUSION: We
      conclude that the upregulation of TNF-alpha and ADAMTS-5, but not ADAMTS-4, may
      play an important role in degenerative CEP-induced low back pain. LEVEL OF
      EVIDENCE: N/A.

PMID- 24732837
TI  - Efficacy of anti-nerve growth factor therapy for discogenic neck pain in rats.
AB  - STUDY DESIGN: Immunohistological analysis of the cervical dorsal root ganglia
      (DRG). OBJECTIVE: To investigate immunohistologically in rats whether intradiscal
      administration of anti-nerve growth factor (NGF) antibody in injured cervical
      intervertebral discs (IVDs) suppresses pain-related peptide expression in DRG
      neurons. SUMMARY OF BACKGROUND DATA: Neck pain can involve the entire neck and
      become chronic and intractable. Cervical disc degeneration is a primary cause of
      neck pain, and pain-related mediators, such as NGF, have been correlated with
      discogenic pain. METHODS: We examined Sprague-Dawley rats that received 10
      punctures in the C5-C6 IVD, and were treated with saline (puncture group) or an
      anti-NGF antibody (anti-NGF group). The retrograde neurotracer Fluoro-Gold (FG)
      was then injected into the C5-C6 IVD. In addition, we examined a sham group that
      did not receive punctures (disc nonpuncture). The C2-C7 DRG were harvested 1 week
      after surgery and immunostained for calcitonin gene-related peptide (CGRP), a
      marker for peptide-containing neurons. We determined for each group the
      percentages of FG-labeled DRG neurons that were CGRP-immunoreactive (CGRP-ir).
      RESULTS: FG-labeled neurons innervating the C5-C6 IVD were found in all C2-C7 DRG
      examined. The percentage of FG-labeled CGRP-ir DRG neurons in the puncture group
      was significantly higher than that observed in the sham (P < 0.001) and anti-NGF
      groups (P < 0.001), but there was no significant difference between the sham and
      anti-NGF groups (P > 0.05). Therefore, intradiscal administration of anti-NGF
      antibody suppressed CGRP expression the cervical DRG. CONCLUSION: Neurons located
      in the C2-C7 DRG innervated the C5-C6 IVD. These findings indicate that neck pain
      may be derived from degenerated IVDs. Furthermore, intradiscal administration of
      anti-NGF antibody suppressed CGRP expression in the cervical DRG innervating the
      injured IVD. Therefore, inhibiting NGF upregulation in the cervical IVD may be an
      efficient treatment for discogenic neck pain. LEVEL OF EVIDENCE: N/A.

PMID- 24732838
TI  - Influence of spinal cord compression and traumatic force on the severity of
      cervical spinal cord injury associated with ossification of the posterior
      longitudinal ligament.
AB  - STUDY DESIGN: Retrospective review. OBJECTIVE: To evaluate the influence of
      static compression factors and dynamic factors based on the various degrees of
      traumatic force on the cervical spinal cord injury (SCI) in patients with
      ossification of the posterior longitudinal ligament. SUMMARY OF BACKGROUND DATA:
      Spinal cord disorder occurs as a result of various factors, including static
      factors and traumatic force. Discussions about the severity of paralysis
      resulting from SCI must therefore focus on dynamic factors based on the traumatic
      force as well as on static compression factors. However, the past reports did not
      describe the influence of traumatic force in detail. METHODS: Fifty patients
      presenting with cervical SCI associated with ossification of the posterior
      longitudinal ligament were included in this study. The American Spinal Injury
      Association motor score 3 days after injury, the degree of the traumatic force,
      and the spinal cord compression rate were investigated, and the relationships
      among these factors were investigated. RESULTS: Paralysis at the time of injury
      was not determined by static factors alone or by traumatic force alone. The
      severity of paralysis at the time of injury was determined on the basis of a
      combination of both the static factors and the degree of traumatic force.
      CONCLUSION: Both the degree of spinal cord compression and the degree of
      traumatic force were found to be important factors associated with the severity
      of cervical SCI in patients with ossification of the posterior longitudinal
      ligament. LEVEL OF EVIDENCE: 4.

PMID- 24732839
TI  - Comparative radiation exposure using standard fluoroscopy versus cone-beam
      computed tomography for posterior instrumented fusion in adolescent idiopathic
      scoliosis.
AB  - STUDY DESIGN: Retrospective cohort. OBJECTIVE: The objective of this study was to
      define the intraoperative radiation exposure during freehand surgical technique
      with fluoroscopic assistance for placement and confirmation of posterior
      instrumentation in patients with adolescent idiopathic scoliosis and compare data
      with published values using intraoperative cone-beam computed tomography (CBCT)
      for similar cases. SUMMARY OF BACKGROUND DATA: The treatment of idiopathic-like
      scoliosis used freehand placement of posterior instrumentation with fluoroscopic
      confirmation. Computer-assisted navigation systems coupled with intraoperative
      CBCT have been introduced to aid in accurate placement of instrumentation.
      Multiple studies report the improved accuracy of instrumentation using CBCT;
      however, there is a paucity of information regarding the radiation exposure when
      using CBCT in comparison with fluoroscopically assisted freehand technique.
      METHODS: Forty-three idiopathic-like scoliosis operations performed by 4 spine
      surgeons at an academic institution were retrospectively reviewed. Radiation
      exposure was recorded intraoperatively for each case. Effective dose was
      determined using published effective dose to dose-length product conversion
      factors. Values were compared with previous studies reporting radiation exposure
      for similar cases using CBCT for intraoperative navigation and confirmation of
      instrumentation placement. RESULTS: Calculated average effective dose using
      fluoroscopically assisted pedicle screw placement was 0.189 mSv (range, 0.00029
      0.953 mSv; SD = 0.16711) per case. Average radiation exposure time was 26 seconds
      (SD = 18 s) per case, with an average of 11 vertebral levels fused. The
      literature reports effective dose for CBCT ranging from 7.29 to 9.72 mSv per case
      for intraoperative navigation and 14.58 to 19.44 mSv per case for both
      intraoperative navigation and confirmation of screw placement with CBCT.
      CONCLUSION: We have demonstrated that the use of standard fluoroscopy results in
      markedly lower radiation exposure during a standard posterior instrumented fusion
      for idiopathic-like scoliosis than by the use of CBCT; this conclusion is limited
      by the retrospective nature of the study and lack of a control group. LEVEL OF
      EVIDENCE: 4.

PMID- 24732840
TI  - Upper thoracic versus lower thoracic upper instrumented vertebrae endpoints have
      similar outcomes and complications in adult scoliosis.
AB  - STUDY DESIGN: Retrospective review-multicenter database. OBJECTIVE: The purpose
      of this study was to compare the upper thoracic (UT) and lower thoracic (LT)
      upper instrumented vertebrae (UIV) in long fusions to the sacrum for adult
      scoliosis. SUMMARY OF BACKGROUND DATA: The optimal UIV for stopping long fusions
      to the sacrum/pelvis are controversial. Although a UT endpoint may lead to
      greater operative times, blood loss, and higher rates of pseudarthrosis, the risk
      for the development of proximal junctional kyphosis and need for revision surgery
      is likely lower. METHODS: Retrospective analysis of a prospective database of
      patients with adult spinal deformity, Patients were selected on the basis of
      fusions to the sacrum/pelvis with UIV of T1-T6 (UT group) and those with a UIV of
      T9-L1 (LT group). Demographic data, operative details, and radiographical
      outcomes with Scoliosis Research Society scores, and Oswestry Disability Index
      outcomes were collected, as well as complication data were compared. The Fisher
      exact T tests were used for statistical analysis. RESULTS: A total of 198
      patients (UT = 91, LT = 107) with a mean age of 61.6 were followed for an average
      of 2.5 years. Demographic variables were similar between the groups except for
      larger numbers of females in the UT group and a slightly higher body mass index
      in the LT group. Preoperatively, the UT group demonstrated significantly more
      lumbar scoliosis, thoracic scoliosis, and thoracolumbar kyphosis. The UT group
      demonstrated a larger number of fused segments length of stay and longer
      operative times. There was slightly larger volume of blood loss in the UT
      group.The total number of complications and number of revision surgical
      procedures were similar between the groups. The UT group had a higher percentage
      of patients with 2 or more complications. Both groups had similar proximal
      junctional kyphosis angles and number of cases requiring revision for proximal
      junctional kyphosis. Scoliosis Research Society and Oswestry Disability Index
      outcomes were similar between the groups. CONCLUSION: The UT and LT groups had
      similar outcomes. The UT group may have a higher rate of total complications, but
      major complications requiring return to the operative room were similar. The
      length of stay and operative times were higher in the UT group but may have been
      necessarily evidenced by the significantly higher coronal deformity and greater
      thoracolumbar kyphosis in the UT group. LEVEL OF EVIDENCE: 4.

PMID- 24732841
TI  - Administration of microRNA-210 promotes spinal cord regeneration in mice.
AB  - STUDY DESIGN: Experimental animal study of treatment of spinal cord injury (SCI).
      OBJECTIVE: To investigate the therapeutic effects of administering microRNA-210
      (miR-210) to promote angiogenesis in a mouse SCI model. SUMMARY OF BACKGROUND
      DATA: Despite many previous studies regarding SCI, there is no established
      treatment in clinical practice. miRNAs have attracted immense attention because
      of their crucial role in human disease, and they have been proposed as potential
      new therapeutic targets for SCI. METHODS: At specific times after administration,
      mice were analyzed by several methods to examine the distribution of miR-210,
      histological angiogenesis and neurogenesis, functional recovery from SCI, and the
      expression levels of target genes of miR-210. RESULTS: After injection of miR-210
      into the lesion of the injured spinal cord, expression of endogenous miR-210
      increased until 6 days after injection. The administration of miR-210 promoted
      angiogenesis and astrogliosis, and improved functional recovery after SCI
      compared with the noninjected controls. Furthermore, the area made up of axons
      and myelin in the spinal cord tissues caudal to the injury site was larger in
      mice injected with miR-210 than those of the controls. Apoptotic cell death was
      lower in mice administered miR-210. After administration of miR-210, the
      expressions of protein-tyrosine phosphate 1B and ephrin-A3, both gene targets of
      miR-210, were downregulated at the protein level and protein-tyrosine phosphate
      1B expression was also downregulated at the transcriptional level. CONCLUSION:
      MiR-210 might contribute to spinal cord repair by promoting angiogenesis via the
      inhibition of protein-tyrosine phosphate 1B and ephrin-A3. LEVEL OF EVIDENCE:
      N/A.

PMID- 24732842
TI  - Modified T4 hemivertebrectomy for persistent high left shoulder after surgery for
      double thoracic scoliosis.
AB  - STUDY DESIGN: Case report. OBJECTIVE: To surgically regain shoulder balance in
      patients with adolescent idiopathic scoliosis after loss of alignment after
      posterior fusion for Lenke II deformity correction. SUMMARY OF BACKGROUND DATA:
      Shoulder balance is known to have a large effect on patient satisfaction after
      deformity correction. Previous studies have outlined guidelines for determining
      levels of instrumentation to prevent postoperative high left shoulder. However,
      to our knowledge, no study has provided instructions on how to correct coronal
      imbalance in patients with previously fused scoliosis. We describe a case using a
      T4 unilateral pedicle subtraction osteotomy and contralateral Smith-Petersen
      osteotomy to treat high left shoulder in a patient who had previously undergone
      posterior instrumented fusion for adolescent idiopathic scoliosis. METHODS: The
      radiographs and clinical charts were reviewed for a 17-year-old female patient
      treated with a revision fusion and modified T4 hemivertebrectomy for a
      persistently high left shoulder after previous correction of a Lenke II
      idiopathic scoliosis. RESULTS: A reduction in the T1 tilt angle from 19.2 degrees
      to 10.1 degrees  and an improvement in the coronal Cobb angle of the proximal
      thoracic curve from 37 degrees  to 17 degrees  were obtained. Shoulder balance
      was greatly improved. CONCLUSION: A proximal thoracic partial vertebrectomy with
      unilateral pedicle subtraction osteotomy and contralateral Smith-Petersen
      osteotomy is a technique that can be used to successfully correct fixed shoulder
      imbalance after posterior instrumented fusion of a double thoracic adolescent
      idiopathic scoliosis. LEVEL OF EVIDENCE: N/A.

PMID- 24732843
TI  - Two-level spinal osteotomy for severe thoracolumbar kyphosis in ankylosing
      spondylitis. Experience with 48 patients.
AB  - STUDY DESIGN: A retrospective study. OBJECTIVE: To report surgical results for
      severe thoracolumbar kyphosis secondary to ankylosing spondylitis (AS) corrected
      with 2-level spinal osteotomy. SUMMARY OF BACKGROUND DATA: Transpedicular
      osteotomy in the lumbar spine is the major approach to correct kyphosis in AS.
      Most surgical procedures were performed at 1 level and only few literature report
      2-level osteotomy in 1 patient. METHODS: From January 2003 to June 2011, we
      reviewed 48 patients experiencing AS with severe thoracolumbar kyphosis who
      underwent stage 2-level spinal osteotomy in our hospital. The osteotomies were
      performed at T12 and L2 or L1 and L3, according to the apex of kyphosis.
      Preoperative and postoperative height, chin-brow vertical angle, sagittal
      balance, and the sagittal Cobb angle of the vertebral osteotomy segment were
      documented. Intraoperative, postoperative, and general complications were
      recorded. RESULTS: The chin-brow vertical angle improved from 65.0 degrees  +/-
      28.0 degrees  to 5.0 degrees +/- 10.0 degrees  (P = 0.000) and the sagittal
      imbalance distance improved from 26.9 +/- 10.4 cm to 10.6 +/- 5.6 cm (P = 0.000).
      The mean amount of correction was 24.9 degrees  at the superior site of the
      osteotomy and 38.1 degrees  at the inferior site of the osteotomy.
      Postoperatively, all patients could walk with horizontal vision and lie on their
      backs. No major acute complications such as death or complete paralysis occurred.
      Five patients experienced complications such as infections (n = 1) and
      cerebrospinal fluid leaks (n = 4). Both Oswestry Disability Index and Scoliosis
      Research Society scores improved largely. Fusion at the osteotomy site was
      achieved in each patient, and no implant failures were noted. CONCLUSION: Single
      stage 2-level osteotomy can effectively and safely correct kyphotic deformities
      of the thoracolumbar spine caused by AS. LEVEL OF EVIDENCE: 3.

PMID- 24732844
TI  - Sagittal standing posture, back pain, and quality of life among adults from the
      general population: a sex-specific association.
AB  - STUDY DESIGN: A prospective radiographical study of sagittal standing posture
      among adults consecutively recruited from the general population. OBJECTIVE: To
      analyze the relation of suboptimal sagittal standing posture with back pain and
      health-related quality of life in general adult males and females. SUMMARY OF
      BACKGROUND DATA: Clinical studies have shown the association of sagittal standing
      posture with pain and reduced quality of life, but this relation has not been
      assessed in the general adult population. METHODS: As part of the EPIPorto
      population-based study of adults, 178 males and 311 females were evaluated. Age,
      education, and body mass index were recorded. Radiographical data collection
      consisted of 36-in. standing sagittal radiographs. Creation of 3 groups for
      individual spinopelvic parameters was performed (low, intermediate, or high), and
      1 of 4 sagittal types of postural patterns attributed to each participant
      (Roussouly classification). Back pain prevalence and severity were assessed on
      the basis of self-reported data and health-related quality of life using 2 main
      components of the 36-Item Short Form Health Survey. RESULTS: In males,
      differences in back pain severity were observed only among pelvic tilt/pelvic
      incidence ratio groups. Females presenting high pelvic incidence and sacral slope
      exhibited higher odds of severe back pain than those with intermediate values
      (adjusted odds ratios = 2.21 and 2.15; 95% confidence interval, 1.24-3.97 and
      1.21-3.86; respectively). Sagittal vertical axis showed the largest differences
      in physical quality of life of females: high group had 8.8 lower score than the
      low group (P < 0.001), but this result lost statistical significance after
      adjustment for age, education, and body mass index. CONCLUSION: Sagittal standing
      posture was not consistently associated with quality of life measures in males.
      Increased pelvic incidence and sacral slope may be involved in causing severe
      back pain among females. Monitoring sagittal postural parameters has limited
      usefulness as a screening tool for causes of unspecific musculoskeletal symptoms
      in the general adult population. LEVEL OF EVIDENCE: 3.

PMID- 24732845
TI  - Use of Department of Veterans Affairs administrative data to identify veterans
      with acute low back pain: a pilot study.
AB  - STUDY DESIGN: This work compared administrative data obtained from the Department
      of Veterans Affairs (VA) databases with structured chart review. OBJECTIVE: We
      set out to determine whether a decision tool using administrative data could
      discriminate acute from nonacute cases among the many patients seen for a low
      back pain (LBP)-related diagnosis. SUMMARY OF BACKGROUND DATA: Large health care
      systems' databases present an opportunity for conducting research and planning
      operations related to the management of highly burdensome conditions. An
      efficient method of identifying cases of acute LBP in these databases may be
      useful. METHODS: This was a retrospective review of all consecutive Iraq and/or
      Afghanistan Veterans seen in a VA primary care service during a 6-month period.
      Administrative data were extracted from VA databases. Patients with at least 1
      encounter that was coded with at least 1 LBP-related ICD-9 code were included.
      Structured chart review of electronic medical record free text was the "gold
      standard" to determine acute LBP cases. Logistic regression models were used to
      assess the association of administrative data variables with chart review
      findings. RESULTS: We obtained complete data on 354 patient encounters, of which
      83 (23.4%) were designated acute upon chart review. No diagnostic code was more
      likely to be used in acute cases than nonacute. We identified an administrative
      data model of 18 variables that were significant and positively associated with
      an acute case (C-statistic = 0.819). A reduced model of 5 variables including a
      lumbar magnetic resonance imaging order, tramadol prescription, skeletal muscle
      relaxant prescription, physical therapy order, and addition of a new LBP-related
      ICD-9 code to the electronic medical record remained reasonable (C-statistic =
      0.784). CONCLUSION: Our results suggest that a decision model can identify acute
      from nonacute LBP cases in Veterans using readily available VA administrative
      data. LEVEL OF EVIDENCE: N/A.

PMID- 24732846
TI  - Patients' expectations of cervical spine surgery.
AB  - STUDY DESIGN: Cross-sectional analysis of patients' expectations of cervical
      spine surgery using the Hospital for Special Surgery Cervical Spine Surgery
      Expectations Survey (Expectations Survey). OBJECTIVE: To preoperatively describe
      patients' long-term expectations of surgery in terms of demographic, clinical,
      and psychological characteristics. SUMMARY OF BACKGROUND DATA: Although important
      components of patient-centered care, few studies have systematically considered
      patients' expectations of cervical spine surgery. METHODS: Several days before
      surgery, 150 patients completed the Expectations Survey, which is composed of 20
      physical and psychological items; scores range from 0 to 100, and higher scores
      reflect choosing more items and more improvement (i.e., more expectations).
      Patients completed additional questionnaires addressing demographic,
      psychological, and clinical status, including disability due to pain with the
      Neck Disability Index (NDI) and overall physical and mental health with the 12
      item Short Form Health Survey. RESULTS: Mean age was 54 years, and 61% were
      males. The most commonly chosen items were relieve neck (87%) and upper extremity
      (85%) pain, stop the spine condition from getting worse (97%), and remove the
      control the spine condition had on life (96%). Twenty-three percent of patients
      chose all 20 items, 39% chose 16 to 19 items, and 38% chose 15 or fewer items. In
      multivariate analysis, patients were more likely to choose more items if they
      were younger (odds ratio [OR] = 2.2; 95% confidence interval [CI], 1.2-4.0; P =
      0.01), had worse NDI scores (OR = 6.5; 95% CI, 3.2-13.2; P < 0.0001), and had
      worse SF-12 Physical (OR = 1.9; 95% CI, 1.0-3.6; P = 0.05) and Mental Health
      scores (OR = 2.0; 95% CI, 1.1-3.6; P = 0.02). The Expectations Survey scores
      ranged from 10 to 100, and the mean score was 65 +/- 24. In multivariate
      analysis, patients were more likely to have higher scores if they were younger
      (OR = 2.8; 95% CI, 1.4-6.0; P = 0.006) and had worse NDI scores (OR = 6.0; 95%
      CI, 2.8-13.2; P < 0.0001). CONCLUSION: Multiple clinical variables were
      associated with expectations, with younger age and more disability due to pain
      being the most consistently associated with more expectations. LEVEL OF EVIDENCE:
      3.

PMID- 24732847
TI  - Pedicle screw versus hybrid construct instrumentation in adolescent idiopathic
      scoliosis: meta-analysis of thoracic kyphosis.
AB  - STUDY DESIGN: A quantitative meta-analysis was conducted on publishing studies
      reporting results of spinal surgery in adolescent idiopathic scoliosis with
      instrumentation of pedicle screw or hybrid construct. OBJECTIVE: The primary
      objective is to get overview of the power to restore thoracic kyphosis using 2
      different instrumentations. SUMMARY OF BACKGROUND DATA: During the past years,
      surgery has mainly focused on correcting the coronal curve, but nowadays, the
      aims of posterior fusion and instrumentation are to achieve a stable, well
      balanced spine in the coronal as well as in the sagittal planes. METHODS: A
      PubMed and EMBASE search was conducted using combinations of the key words
      "hybrid construct" or "pedicle screw" with "adolescent idiopathic scoliosis" up
      to October 2013. A hand search of reference lists of obtained articles was also
      performed. RESULTS: A total of 24 studies were identified and included in this
      meta-analysis. Of this, 12 included pedicle screw group only, 5 included hybrid
      construct group only, and 7 included both groups. The total number of patients
      was 1615. Age ranged from 9 to 26 years, with a mean of 15. For pedicle screw
      group, we got standard mean difference (SMD) as 0.40 (95% confidence interval,
      0.31-0.50); I= 91.4%. For hybrid construct group, we got SMD as 0.15 (95%
      confidence interval, 0.04-0.26). Both intervals of SMD lay in positive value
      side. Overall SMD was 0.30 (95% confidence interval, 0.23-0.37). The positive
      value of SMD means thoracic kyphosis improves after surgery, whereas negative
      value means kyphosis loss after surgery. CONCLUSION: There is overall tendency
      for both instrumentations to restore thoracic kyphosis. Hybrid construct seems to
      be more powerful in restoring kyphosis than pedicle screw. Preoperative important
      factor was found to be reasonably distributed or balanced. For operative factor,
      rod stiffness, fashion of hybrid construct, in situ bending, and rod rotation
      maneuver could have influence on results of kyphosis in different ways. Loss of
      correction and limited restoration of loss may do exist after correction. LEVEL
      OF EVIDENCE: 3.

PMID- 24732848
TI  - Radiofrequency denervation for facet joint low back pain: a systematic review.
AB  - STUDY DESIGN: A systematic review and meta-analysis of randomized controlled
      trials. OBJECTIVE: To assess treatment effects (benefits and harms) of
      radiofrequency denervation for patients with facet joint-related chronic low back
      pain. SUMMARY OF BACKGROUND DATA: There is no consensus regarding the treatment
      efficacy of facet joint radiofrequency denervation (FJRD) and how it compares
      with nerve blockades and joint infiltration with anesthetics and/or
      corticosteroids. METHODS: We searched the Cochrane Central Register of Controlled
      Trials, MEDLINE, EMBASE, and LILACS for randomized controlled trials that
      compared FJRD with blockades, infiltrations, or placebo. Primary outcomes were
      pain, functional status, and quality of life. Secondary outcomes were cost
      effectiveness and complications. RESULTS: Fifteen studies were selected and 9
      were eligible. Overall quality of evidence was rated low to moderate. The
      evidence favored FJRD regarding pain control. There was no sufficient evidence
      for cost-effectiveness and complications. CONCLUSION: The available evidence
      reviewed in this study should be interpreted with caution. The data indicate that
      FJRD is more effective than placebo in pain control and functional improvement
      and is also possibly more effective than steroid injections in pain control.
      Complications and adverse effects were not sufficiently reported to allow
      comparisons, and there was no evidence for cost-effectiveness. High-quality
      randomized controlled trials addressing pain, function, quality of life,
      complications, and cost-effectiveness are urgently needed. LEVEL OF EVIDENCE: 1.

PMID- 24732849
TI  - National trends in spinal fusion for pediatric patients with idiopathic
      scoliosis: demographics, blood transfusions, and in-hospital outcomes.
AB  - STUDY DESIGN: Analysis of population-based national hospital discharge data
      collected for the Nationwide Inpatient Sample database. OBJECTIVE: To analyze
      trends in spinal fusion for pediatric patients with idiopathic scoliosis on a
      national level with regard to demographics, blood transfusions, and in-hospital
      outcomes. SUMMARY OF BACKGROUND DATA: Spinal fusion for pediatric patients with
      idiopathic scoliosis is required for rapid curve progression. For such patients
      and their families, blood transfusions and complications are important aspects of
      the surgery. METHODS: The Nationwide Inpatient Sample database was used to
      identify pediatric patients with idiopathic scoliosis who underwent spinal fusion
      from 2000 to 2009 using the International Classification of Diseases, Ninth
      Revision, Clinical Modification codes. Demographics of the patients were
      retrieved. Trends in demographics, blood transfusion methods, and in-hospital
      outcomes were analyzed. RESULTS: The total number of patients included in this
      study was 43,983. A total of 30.4% of patients received a blood transfusion.
      Predonated autologous blood transfusions decreased over time, whereas
      perioperative autologous blood transfusions increased over time (P < 0.05,
      respectively). The in-hospital overall complication rate was 14.4%. The
      respiratory complication rate was the highest among complications; however, the
      rate decreased over time (P = 0.003). In-hospital blood transfusion,
      complication, and mortality rates were high in certain subgroups of patients,
      such as those with increased Elixhauser Comorbidity Score and those who underwent
      anterior and posterior fusion. The mean length of hospital stay decreased over
      time (P = 0.043). CONCLUSION: During the last decade, 30% of pediatric patients
      with idiopathic scoliosis who underwent spinal fusion received some type of blood
      transfusion; and strategies for blood transfusion methods have changed over the
      years. A decreasing trend in the respiratory complication rate and reduction in
      length of hospital stay may indicate better postoperative care. LEVEL OF
      EVIDENCE: 3.

PMID- 24732850
TI  - Saphenous nerve somatosensory evoked potentials: a novel technique to monitor the
      femoral nerve during transpsoas lumbar lateral interbody fusion.
AB  - STUDY DESIGN: A retrospective analysis of a case series was performed. OBJECTIVE:
      To describe a novel technique to monitor femoral nerve function by analyzing the
      saphenous nerve somatosensory evoked potential (SSEP) during transpsoas surgical
      exposures of the lumbar spine. SUMMARY OF BACKGROUND DATA: During transpsoas
      direct lateral approaches to the lumbar spine, electromyography monitoring is
      frequently advocated; however, sensory and motor neurological complications are
      still being reported. Femoral nerve injury remains a feared complication at the
      L3-L4 and L4-L5 levels. The current neurophysiological monitoring modalities are
      not specific or sensitive enough to predict these injuries after the retractors
      are placed. The authors have developed a technique that is hypothesized to reduce
      femoral nerve injuries caused by retractor compression by adding saphenous nerve
      SSEPs to their neurophysiological monitoring paradigm. METHODS: Institutional
      review board approval was granted for this study and the medical records along
      with the intraoperative monitoring reports from 41 consecutive transpsoas lateral
      interbody fusion procedures were analyzed. The presence or absence of
      intraoperative changes to the saphenous nerve SSEP was noted and the
      postoperative symptoms and physical examination findings were noted. RESULTS:
      SSEP changes were noted in 5 of the 41 surgical procedures, with 3 of the
      patients waking up with a femoral nerve deficit. None of the patients with stable
      SSEP's developed sensory or motor deficits postoperatively. No patient in this
      series demonstrated intraoperative electromyography changes indicative of an
      intraoperative nerve injury. CONCLUSION: Saphenous nerve SSEP monitoring may be a
      beneficial tool to detect femoral nerve injury related to transpsoas direct
      lateral approaches to the lumbar spine. LEVEL OF EVIDENCE: 4.

PMID- 24732851
TI  - Transverse process hooks at upper instrumented vertebra provide more gradual
      motion transition than pedicle screws.
AB  - STUDY DESIGN: Biomechanical study in a porcine model. OBJECTIVE: To determine
      whether transverse process hooks (TPHs) placed at the proximal end of a long
      posterior spinal fusion construct provide a more gradual transition to normal
      motion of the adjacent cephalad motion segment compared with an all pedicle screw
      (APS) construct. SUMMARY OF BACKGROUND DATA: Proximal junctional kyphosis after
      instrumentation with long posterior spinal constructs has been increasingly
      associated with incidence of adjacent segment pathologies. Clinical studies have
      suggested that proximal anchor type may affect the incidence of proximal
      junctional kyphosis. METHODS: Biomechanical tests were conducted on porcine
      thoracic spines before and after implantation of a long spinal fusion construct.
      In all specimens, dual long rods (Co-Cr) were implanted posteriorly using pedicle
      screws at T7-T15. Upper instrumented vertebra, T6, received either TPHs (n = 7)
      or pedicle screws (APSs) (n = 6). Each specimen was tested in flexion-extension
      then lateral bending. Moments were applied, and vertebral displacements were
      recorded. Range of motion (ROM) and stiffness (K) were determined for each motion
      segment. Differences between TPH and APS at the transition were determined using
      t tests. RESULTS: In flexion-extension, ROM at the most proximal instrumented
      motion segment was 9% of control for APS versus 21% of control for TPH.
      Difference between APS and TPH at UIV was 0.5 degrees  (P < 0.008). Stiffness of
      TPH at T6-T7 was significantly lower than APS in FE (P < 0.003). For APS, the
      greatest mean ROM occurred at the first uninstrumented segment, whereas TPH
      maintained the pattern of monotonic increases in mean ROM from distal to
      proximal. CONCLUSION: TPHs at the upper instrumented vertebra provided a more
      gradual transition to normal motion compared with pedicle screws in long
      posterior spinal fusion constructs. TPH at the upper instrumented vertebra may be
      postulated to decrease the incidence of postoperative proximal junctional
      kyphosis compared with APS. LEVEL OF EVIDENCE: N/A.

PMID- 24732852
TI  - Craniopelvic alignment in elderly asymptomatic individuals: analysis of 671
      cranial centers of gravity.
AB  - STUDY DESIGN: Prospective radiographical analysis using the cranial center of
      gravity (CCG) of sagittal vertical axis (SVA) in elderly asymptomatic
      individuals. OBJECTIVE: To determine sex differences and age-related correlations
      of CCG and relationships between CCG and other spinopelvic parameters/health
      related quality of life (HRQOL) measures. SUMMARY OF BACKGROUND DATA: Few studies
      have investigated CCG in a relatively large sample of elderly asymptomatic
      individuals. METHODS: Six hundred seventy-one healthy participants older than 50
      years (mean age, 72.9 yr; range, 50-92 yr) were enrolled. Whole-spine standing
      radiographs were obtained. The following radiographical measurements were
      obtained: (1) CCG-C7 SVA, (2) C7-SVA, (3) CCG-SVA, (4) C2-C7 lordosis angle, (5)
      thoracic kyphosis, (6) lumbar lordosis, (7) pelvic incidence, and (8) sacral
      slope. HRQOL measures included the EuroQol-5D and Oswestry Disability Index.
      Pearson product-moment correlation coefficients were calculated between pairs of
      radiographical measures and HRQOL. RESULTS: Sex differences were observed in CCG
      C7 SVA, CCG-SVA, C2-C7 Cobb angle, thoracic kyphosis, and pelvic incidence. Three
      SVA parameters (CCG-C7 SVA, C7-SVA, CCG-SVA) rapidly increased between seventh
      and ninth decades and were approximately 40, 80, and 120 mm, respectively, in the
      ninth decade. Age-related correlations were observed for all parameters without
      pelvic incidence, and the CCG measurement correlated the most with age.
      Furthermore, CCG-SVA correlated with other spinopelvic measurements and HRQOL.
      CONCLUSION: Age-related changes and sex difference in craniopelvic alignment were
      analyzed. Craniopelvic alignment became rapidly positive with age, particularly
      in the eighth decade. The CCG measurement correlated the most with age and may be
      a useful index marker of global spinal balance in decision making for surgical
      treatment of adult deformity involving cervical and thoracolumbar lesions. LEVEL
      OF EVIDENCE: 4.

PMID- 24732853
TI  - Transcranial magnetic stimulation of the motor cortex correlates with objective
      clinical measures in patients with cervical spondylotic myelopathy.
AB  - STUDY DESIGN: Prospective cohort study. OBJECTIVE: To assess the correlation
      between central motor conduction time (CMCT) and various subjective and objective
      clinical assessment measures in patients undergoing decompressive surgery for
      cervical spondylotic myelopathy (CSM). SUMMARY OF BACKGROUND DATA: CSM can cause
      a spectrum of neurological deficits among individuals. Subjective clinical
      assessments of disease severity may lack the sensitivity of objective tests.
      Transcranial magnetic stimulation provides objective electrophysiological data on
      the integrity of the corticospinal tracts, which may be useful for monitoring
      disease progression or neurological improvement after surgery. METHODS: Patients
      undergoing surgical decompression for CSM underwent subjective and objective
      testing before surgery and at 1, 3, 6, and 12 months after surgery. Subjective
      measures included modified Japanese Orthopaedic Association score, Neck
      Disability Index, Nurick grade, and visual analogue scale score. Objective
      measures included CMCT as measured using transcranial magnetic stimulation, the
      10-m walk test, the 9-hole peg task, and the grip and release test. Primary
      outcome was the correlation between CMCT and subjective or objective measures at
      preoperative and postoperative time points. Secondary outcome was the correlation
      between preoperative CMCT and performance in subjective or objective testing
      after surgical intervention. RESULTS: Improvement in both subjective and
      objective measures was observed after surgery. CMCT correlated with other
      objective measures (10-m walk test, 9-hole peg task, and grip and release test)
      both at baseline and after decompressive surgery in these 17 patients with CSM.
      Patients with high baseline CMCTs were associated with poor performance on the 10
      m walk test, 9-hole peg task, and grip and release test. Modified Japanese
      Orthopaedic Association score correlated with CMCT at baseline but not after
      surgical intervention. CMCT was not associated with other subjective measures,
      such as Neck Disability Index, Nurick grade, and visual analogue scale score, at
      preoperative or postoperative time points. CONCLUSION: CMCT as measured by
      transcranial magnetic stimulation is a responsive objective assessment of CSM. It
      can be used to monitor disease severity and neurological function before and
      after surgical intervention. Prolonged baseline CMCT may be associated with worse
      surgical outcomes. LEVEL OF EVIDENCE: 2.

PMID- 24732854
TI  - Sagittal spinopelvic malalignment in Parkinson disease: prevalence and
      associations with disease severity.
AB  - STUDY DESIGN: Prospective study. OBJECTIVE: Our objectives were to evaluate the
      prevalence of sagittal spinopelvic malalignment in a consecutive series of
      patients with Parkinson disease (PD) and to identify factors associated with
      sagittal spinopelvic deformity in this population. SUMMARY OF BACKGROUND DATA: PD
      is a degenerative neurological condition characterized by tremor, rigidity,
      bradykinesia, and loss of postural reflexes. The prevalence of spinal deformity
      in PD is higher than that of age-matched adults without PD. METHODS: This study
      was a prospective assessment of consecutive patients with PD presenting to a
      neurology clinic during 12 months. Inclusion criteria included age more than 21
      years and diagnosis of PD. Age- and sex-matched control group was selected from
      patients with cervical spondylosis. Clinical and demographic factors were
      collected including Unified Parkinson Disease Rating Scale score and Hoehn and
      Yahr stage. Full-length standing spine radiographs were assessed. Patients were
      grouped into either low C7 sagittal vertical axis (SVA) (<5 cm) or high C7 SVA
      (>=5 cm) and into matched (<=10 degrees ) or mismatched (>10 degrees ) pelvic
      incidence (PI)-lumbar lordosis. RESULTS: Eighty-nine patients met criteria (41
      males/48 females), including 52 with low C7 SVA and 37 with high C7 SVA.
      Significantly higher prevalence of high C7 SVA was found in PD (41.6 vs. 16.8%; P
      < 0.001). The high C7 SVA group was significantly older (72.4 vs. 65.1 yr; P <
      0.001) and had a higher proportion of females (68% vs. 44%; P = 0.034), greater
      severity of PD based on Hoehn and Yahr stage (1.89 vs. 1.37; P < 0.001) and
      Unified Parkinson Disease Rating Scale (30.5 vs. 17.2; P = 0.002. Unified
      Parkinson Disease Rating Scale significantly correlated with C7 SVA (r = 0.474).
      Compared with the matched (<=10 degrees ) PI-lumbar lordosis group, the mismatch
      PI-lumbar lordosis group had higher C7 SVA, higher PI, higher pelvic tilt, lower
      lumbar lordosis, and lower thoracic kyphosis (P <= 0.003). CONCLUSION: Patients
      with PD have a high prevalence of sagittal spinopelvic malalignment than control
      group patients. Greater severity of PD is associated with sagittal spinopelvic
      malalignment. LEVEL OF EVIDENCE: 3.

PMID- 24732855
TI  - Surgical treatment of Lenke 1 thoracic adolescent idiopathic scoliosis with
      maintenance of kyphosis using the simultaneous double-rod rotation technique.
AB  - STUDY DESIGN: Retrospective analysis of a prospectively collected, consecutive,
      nonrandomized series of patients. OBJECTIVE: To assess the surgical outcomes of
      the simultaneous double-rod rotation technique for treating Lenke 1 thoracic
      adolescent idiopathic scoliosis (AIS). SUMMARY OF BACKGROUND DATA: With the
      increasing popularity of segmental pedicle screw spinal reconstruction for
      treating AIS, concerns regarding the limited ability to correct hypokyphosis have
      also increased. METHODS: A consecutive series of 32 patients with Lenke 1 main
      thoracic AIS treated with the simultaneous double-rod rotation technique at our
      institution was included. Outcome measures included patient demographics,
      radiographical measurements, and Scoliosis Research Society questionnaire scores.
      RESULTS: All 32 patients were followed up for a minimum of 2 years (average, 3.6
      yr). The average main thoracic Cobb angle correction rate and the correction loss
      at the final follow-up were 67.8% and 3.3 degrees , respectively. The average
      preoperative thoracic kyphosis (T5-T12) was 11.9 degrees , which improved
      significantly to 20.5 degrees  (P < 0.0001) at the final follow-up. An increase
      in thoracic kyphosis was significantly correlated with an increase in lumbar
      lordosis at the final follow-up (r = 0.42). The average preoperative vertebral
      rotation angle was 19.7 degrees , which improved significantly after surgery to
      14.9 degrees  (P = 0.0001). There was no correlation between change in thoracic
      kyphosis and change in apical vertebral rotation (r =-0.123). The average
      preoperative total Scoliosis Research Society questionnaire score was 3.0, which
      significantly improved to 4.4 (P < 0.0001) at the final follow-up. Throughout
      surgery and even after, there were no instrumentation failures, pseudarthrosis,
      infection of the surgical site, or clinically relevant neurovascular
      complications. CONCLUSION: The simultaneous double-rod rotation technique for
      treating Lenke 1 AIS provides significant sagittal correction of the main
      thoracic curve while maintaining sagittal profiles and correcting coronal and
      axial deformities. LEVEL OF EVIDENCE: 4.

PMID- 24732856
TI  - The incidence and risk factors for short-term morbidity and mortality in
      pediatric deformity spinal surgery: an analysis of the NSQIP pediatric database.
AB  - STUDY DESIGN: Retrospective review of a prospective cohort. OBJECTIVE: To
      determine the incidence and risk factors for 30-day morbidity and mortality after
      pediatric deformity spinal surgery. SUMMARY OF BACKGROUND DATA: Pediatric
      deformity spinal surgery is generally considered a safe and effective treatment
      option. The rising costs associated with spinal surgery and related perioperative
      complications have received national attention. Few studies with standardized
      definitions and data collection methods exist. METHODS: A large, multicenter
      clinical registry specifically designed to collect pediatric surgical outcomes
      was queried for all patients undergoing spinal deformity surgery in 2012. Current
      Procedural Terminology codes were used to select patients undergoing anterior,
      posterior, and combined fusions. Detailed patient and case characteristics were
      analyzed. Thirty-day morbidity and mortality rates were calculated. Univariate
      and multivariate logistic regression analyses were used to identify patient
      characteristics, comorbidities, and operative variables predictive of
      complication. RESULTS: In total, 2005 pediatric patients undergoing deformity
      spinal fusion were included. The rate of 30-day complications was 10.0%; with a
      mortality rate of 0.15% (3 patients), a morbidity rate of 8.4%, reoperation rate
      of 3.74%, and readmission rate of 3.94%. The morbidity rate was highest in the
      neuromuscular group (13.09%) and lowest in the idiopathic cohort (5.69%), P <
      0.01). Compared with posterior fusions, anterior fusions and those extending to
      the pelvis were associated with higher complication rates (P < 0.01). Risk
      factors for complication included hepatobiliary disease (P = 0.03), cognitive
      impairment (P = 0.02), elevated American Society of Anesthesiologists class (P <
      0.01), and prolonged operative time (P < 0.01). CONCLUSION: The overall rate of
      30-day morbidity after pediatric spinal deformity surgery was 10%. Multiple
      patient comorbidities and surgical duration and invasiveness were associated with
      an increased complication risk. These data may aid in the informed consent
      process, facilitate patient risk assessment, and allow quality comparisons
      between surgeons and institutions. LEVEL OF EVIDENCE: 2.

PMID- 24732858
TI  - Rehabilitation following surgery for lumbar spinal stenosis. A Cochrane review.
AB  - STUDY DESIGN: A systematic review of randomized controlled trials. OBJECTIVE: To
      determine the effects of active rehabilitation on functional outcome after lumbar
      spinal stenosis surgery when compared with "usual postoperative care." SUMMARY OF
      BACKGROUND DATA: Surgery rates for lumbar spinal stenosis have risen, yet
      outcomes remain suboptimal. Postoperative rehabilitation has been suggested as a
      tool to improve postoperative function but, to date, there is limited evidence to
      support its use. METHODS: CENTRAL (The Cochrane Library), the Cochrane Back
      Review Group Trials Register, MEDLINE, EMBASE, CINAHL, and PEDro electronic
      databases were searched. Randomized controlled trials comparing the effectiveness
      of active rehabilitation with usual care in adults with lumbar spinal stenosis
      who had undergone primary spinal decompression surgery were included. Two authors
      independently selected studies, assessed the risk of bias, and extracted the data
      in line with the recommendations of the Cochrane Back Review Group. Study results
      were pooled in a meta-analysis when appropriate using functional status as the
      primary outcome, with secondary outcomes including measures of leg pain, low back
      pain, and global improvement/general health. The GRADE approach was used to
      assess the quality of the evidence. RESULTS: Our searches yielded 1726 articles,
      of which 3 studies (N = 373 participants) were suitable for inclusion in meta
      analysis. All included studies were deemed to have low risk of bias; no study had
      unacceptably high dropout rates. There was moderate evidence suggesting that
      active rehabilitation was more effective than usual care in improving both short-
      and long-term functional status after surgery. Similar findings were noted for
      secondary outcomes, including short-term improvement in low back pain and long
      term improvement in both low back pain and leg pain. CONCLUSION: We obtained
      moderate-quality evidence indicating that postoperative active rehabilitation
      after decompression surgery for lumbar spinal stenosis is more effective than
      usual care. Further work is required particularly with respect to the cost
      effectiveness of such interventions. LEVEL OF EVIDENCE: 1.

PMID- 24732859
TI  - Defining clinically relevant values for developmental spinal stenosis: a large
      scale magnetic resonance imaging study.
AB  - STUDY DESIGN: Case-control study. OBJECTIVE: The aim of this study was to define
      clinically relevant relative and critical (absolute) magnetic resonance imaging
      values of lumbar spinal stenosis in a cohort of 100 surgical cases and 100
      asymptomatic controls. SUMMARY OF BACKGROUND DATA: Developmental spinal stenosis
      is a precipitating factor in patients presenting with lumbar canal stenosis. Yet,
      due to a lack of agreement on definitions and methods of assessment, as well as
      ethnic-specific normative values, its prevalence and significance is not known.
      METHODS: This was a case-control study comparing 100 age and sex-matched
      asymptomatic, volunteers with that of 100 patients who underwent surgery for
      spinal stenosis. All patients were of Chinese ethnicity and their details were
      blinded to 2 observers. Spinal stenosis parameters were measured on the basis of
      axial (pedicle level) and sagittal (midsagittal) magnetic resonance images.
      RESULTS: Anteroposterior spinal canal diameters change with levels. At each
      level, patients were found to have significantly narrower anteroposterior canal
      diameters than controls. By use of receiver operating characteristic curve, we
      defined developmental spinal stenosis if the anteroposterior canal diameter was
      at L1 <20 mm, L2 <19 mm, L3 <19 mm, L4 <17 mm, L5 <16 mm, and at S1 <16 mm on the
      basis of a value including 50% of controls and demonstrated best sensitivity and
      specificity. Furthermore, for L4, L5, and S1, critical stenosis values could be
      defined, below which almost all subjects needed surgery, these were L4 <14 mm, L5
      <14 mm, and S1 <12 mm. CONCLUSION: This is the largest magnetic resonance imaging
      based study with standardized measurements and comparable groups to determine
      clinically relevant magnetic resonance imaging criteria for lumbar spinal
      stenosis. The findings strongly suggest that developmental stenosis plays an
      important role in the pathogenesis of symptomatic spinal stenosis. Critical
      values of stenosis below which symptoms were highly likely were defined. These
      will need to be validated by longitudinal studies in future. However, they may
      possess clinical utility in determining the appropriate levels requiring canal
      widening surgery. LEVEL OF EVIDENCE: 3.

PMID- 24732860
TI  - Ten-year follow-up of strengthening versus flexibility exercises with or without
      abdominal bracing in recurrent low back pain.
AB  - STUDY DESIGN: Randomized prevention trial. OBJECTIVE: To compare the long-term
      effect of strengthening versus flexibility exercises and to evaluate the
      additional effect of abdominal bracing in recurrent low back pain (LBP). SUMMARY
      OF BACKGROUND DATA: No conclusions could be made regarding appropriate exercise
      types or parameters in recurrent LBP. Abdominal bracing increases trunk
      stiffness; however, its long-term effect has not been evaluated in recurrent LBP
      yet. METHODS: Six hundred patients with recurrent LBP participated. They were
      randomized into 4 groups-150 patients (age: 42.5 +/- 12.7) performed
      strengthening exercises; 150 patients (age: 41.3 +/- 11.5) performed flexibility
      exercises; 150 patients (age: 41.0 +/- 13.2) performed strengthening exercises
      and used abdominal bracing in daily activities/exercises; and 150 patients (age:
      40.6 +/- 12.3) performed flexibility exercises and used abdominal bracing in
      daily activities/exercises. At the beginning of the study and at the end of 10
      consecutive years were recorded 6 outcomes-frequency, intensity, and duration of
      pain, as well as frequency, intensity, and duration of exercises. RESULTS:
      Regarding the first 4 outcomes-all groups showed improvement from the beginning
      to the second year, but worsening from the second to the 10th year; there was no
      difference between strengthening and flexibility groups; bracing groups showed
      better results versus nonbracing groups. Intensity, frequency, and duration of
      the pain correlated with each other and with frequency of the exercises, but not
      with exercise duration or intensity. CONCLUSION: The exercise frequency is more
      important than the type, duration, or intensity of the exercise. Abdominal
      bracing adds to the exercise effect. It could be considered as a "preliminary
      muscle back belt on demand" increasing the trunk stiffness and the frequency of
      the trunk muscle contractions/cocontractions without interruption of daily
      activities, which may remind/convince the patients to exercise more frequently.
      Frequent exercising and bracing seems effective long-term prevention advices in
      recurrent LBP. LEVEL OF EVIDENCE: 2.

PMID- 24732861
TI  - Understanding the statistics and limitations of large database analyses.

PMID- 24732862
TI  - GSK-3beta and vitamin D receptor are involved in beta-catenin and snail signaling
      in high glucose-induced epithelial-mesenchymal transition of mouse podocytes.
AB  - BACKGROUND: Epithelial-mesenchymal transition (EMT) is recognized to play an
      important role in diabetic nephropathy (DN). OBJECTIVE: To analyze the roles of
      glycogen synthase kinase 3beta (GSK-3beta), beta-catenin and Snail signaling in
      high glucose (HG)-induced mouse podocytes EMT. METHODS: Differentiated podocytes
      were divided into: the normal glucose group (NG: glucose 5.6mM), the HG groups
      (12.5HG: 12.5mM; 25HG: 25mM; and 50HG: 50mM of glucose), and the osmotic control
      group (NG+M: glucose 5.6mM and mannitol 44.4mM). GSK-3beta, beta-catenin and
      Snail were assessed using semi-quantitative RT-PCR, western blot and
      immunofluorescence. beta-catenin and Snail pathways were assessed after down
      regulating GSK-3beta expression using an inhibitor (LiCl) or a small-interfering
      RNA (siRNA). RESULTS: HG increased GSK-3beta, beta-catenin and Snail expressions,
      and promoted EMT, as shown by decreased nephrin expression (epithelial marker),
      and increased alpha-SMA expression (mesenchymal marker). GSK-3beta inhibitor and
      GSK-3beta siRNA decreased beta-catenin and Snail expressions, and reversed HG
      induced EMT. Immunofluorescence showed that GSK-3beta and beta-catenin did not
      completely overlap; beta-catenin was transferred to the nucleus in the 25HG
      group. VDR seems to be involved in HG-induced beta-catenin nuclear translocation.
      CONCLUSION: Down-regulating GSK-3beta expression decreased beta-catenin and Snail
      expression and reversed HG-induced podocytes EMT. Thus, modulating GSK-3beta
      might be a target to slow or prevent DN. (c) 2014 S. Karger AG, Basel.

PMID- 24732863
TI  - Impact of radical and partial nephrectomy on renal function in patients with
      renal cancer.
AB  - OBJECTIVE: To evaluate renal function in renal cancer patients undergoing radical
      nephrectomy (RN) or partial nephrectomy (PN) (open or laparoscopic - ORN, OPN,
      LRN or LPN) and to identify risk factors contributing to renal function loss.
      METHODS: We analysed 228 consecutive renal cancer patients admitted for OPN, LPN,
      ORN or LRN. The variables analysed were age, gender, weight, type of surgery
      (radical versus partial), type of surgical access (open versus laparoscopic),
      preoperative renal function and history of hypertension, diabetes or malignancy.
      Absolute renal function was calculated as the difference in glomerular filtration
      rate (DeltaGFR) between the renal function before (GFR0) and 12 months after
      surgery (GFR12). The relative renal function of patients undergoing PN and RN was
      evaluated by the change in chronic kidney disease stage. RESULTS: LRN caused the
      greatest loss in absolute renal function, followed by ORN, LPN and OPN. A GFR of
      >=60 ml/min was noted for 90 (68.7%) patients before and 65 (49.6%) patients
      after RN and for 80 (82.5%) patients before and 74 (76.3%) patients after PN. The
      chronic kidney disease stage dropped to 4 or 5 in the case of 6 (4.6%) patients
      who underwent RN and 2 (2.1%) patients who underwent PN. Multivariate analysis
      revealed that only preoperative weight and type of surgery (radical versus
      partial) had a significant impact on renal function. CONCLUSION: Renal function
      significantly decreased in patients undergoing RN, irrespective of the access
      route. Patients with preoperative poor renal function are at risk of
      postoperative end-stage renal disease.

PMID- 24732864
TI  - Lack of serologic evidence to link IgA nephropathy with celiac disease or immune
      reactivity to gluten.
AB  - IgA nephropathy is the most common form of primary glomerulonephritis worldwide.
      Mucosal infections and food antigens, including wheat gluten, have been proposed
      as potential contributing environmental factors. Increased immune reactivity to
      gluten and/or association with celiac disease, an autoimmune disorder triggered
      by ingestion of gluten, have been reported in IgA nephropathy. However, studies
      are inconsistent about this association. We aimed to evaluate the proposed link
      between IgA nephropathy and celiac disease or immune reactivity to gluten by
      conducting a comprehensive analysis of associated serologic markers in cohorts of
      well-characterized patients and controls. Study participants included patients
      with biopsy-proven IgA nephropathy (n = 99), unaffected controls of similar age,
      gender, and race (n = 96), and patients with biopsy-proven celiac disease (n =
      30). All serum specimens were tested for IgG and IgA antibodies to native gliadin
      and deamidated gliadin, as well as IgA antibody to transglutaminase 2 (TG2). Anti
      TG2 antibody-positive nephropathy patients and unaffected controls were
      subsequently tested for IgA anti-endomysial antibody and genotyped for celiac
      disease-associated HLA-DQ2 and -DQ8 alleles. In comparison to unaffected
      controls, there was not a statistically significant increase in IgA or IgG
      antibody reactivity to gliadin in individuals with IgA nephropathy. In addition,
      the levels of celiac disease-specific serologic markers, i.e., antibodies to
      deamidated gliadin and TG2, did not differ between IgA nephropathy patients and
      unaffected controls. Results of the additional anti-endomysial antibody testing
      and HLA genotyping were corroborative. The data from this case-control study do
      not reveal any evidence to suggest a significant role for celiac disease or
      immune reactivity to gluten in IgA nephropathy. 

PMID- 24732865
TI  - FTSPlot: fast time series visualization for large datasets.
AB  - The analysis of electrophysiological recordings often involves visual inspection
      of time series data to locate specific experiment epochs, mask artifacts, and
      verify the results of signal processing steps, such as filtering or spike
      detection. Long-term experiments with continuous data acquisition generate large
      amounts of data. Rapid browsing through these massive datasets poses a challenge
      to conventional data plotting software because the plotting time increases
      proportionately to the increase in the volume of data. This paper presents
      FTSPlot, which is a visualization concept for large-scale time series datasets
      using techniques from the field of high performance computer graphics, such as
      hierarchic level of detail and out-of-core data handling. In a preprocessing
      step, time series data, event, and interval annotations are converted into an
      optimized data format, which then permits fast, interactive visualization. The
      preprocessing step has a computational complexity of O(n x log(N)); the
      visualization itself can be done with a complexity of O(1) and is therefore
      independent of the amount of data. A demonstration prototype has been implemented
      and benchmarks show that the technology is capable of displaying large amounts of
      time series data, event, and interval annotations lag-free with < 20 ms ms. The
      current 64-bit implementation theoretically supports datasets with up to 2(64)
      bytes, on the x86_64 architecture currently up to 2(48) bytes are supported, and
      benchmarks have been conducted with 2(40) bytes/1 TiB or 1.3 x 10(11) double
      precision samples. The presented software is freely available and can be included
      as a Qt GUI component in future software projects, providing a standard
      visualization method for long-term electrophysiological experiments.

PMID- 24732866
TI  - The rapid evolution of treatment strategies for hepatitis C.
AB  - Hepatitis C virus (HCV) treatment took a major step forward at the end of 2013
      with the approvals of the second-generation protease inhibitor simeprevir
      (Olysio) and the nucleotide polymerase inhibitor sofosbuvir (Sovaldi). The
      interferon-free regimen of sofosbuvir and ribavirin is now available for genotype
      2 and 3 patients. This regimen for 12 weeks is highly effective for genotype 2,
      whereas genotype 3 has proven to be more challenging and requires 24 weeks of
      therapy. Genotype 1 patients have reduced exposure to peginterferon-alpha with a
      12-week regimen with sofosbuvir and a 24-week regimen with simeprevir. Genotype
      4, 5, and 6 patients also respond well to the regimen of sofosbuvir,
      peginterferon-alpha, and ribavirin. In another landmark event, the initial
      approval of sofosbuvir included HCV/HIV-1 coinfected patients. Simeprevir and
      sofosbuvir also provide a window to the future with sustained virologic response
      (SVR) rates of >90% for genotype 1 when these agents are combined. Interferon
      free regimens for genotype 1 patients have anticipated approvals in late 2014 or
      early 2015. Clinicians and patients will have the opportunity to discuss and
      select from current treatment options or await upcoming regimens. These potent
      new agents provide the tools to cure HCV for many patients.

PMID- 24732868
TI  - Acid-based parameters on pH-impedance testing predict symptom improvement with
      medical management better than impedance parameters.
AB  - OBJECTIVES: pH-impedance testing detects reflux events irrespective of pH, but
      its value in predicting treatment outcome is unclear. We prospectively evaluated
      subjects treated medically after pH-impedance testing to determine predictors of
      symptom improvement. METHODS: Subjects referred for pH-impedance testing
      completed questionnaires in which dominant symptoms and global symptom severity
      (GSS) were recorded. Acid-reflux parameters (acid-exposure time, AET; symptom
      association by Ghillebert probability estimate, GPE; symptom index, SI) and
      impedance reflux parameters (reflux-exposure time, RET; number of reflux events;
      GPE and SI with impedance data) were extracted. Symptoms and GSS were
      prospectively reevaluated after medical therapy. Univariate and multivariate
      analyses determined predictors of GSS improvement following medical management.
      RESULTS: Over 5 years, 128 subjects (mean 53.3+/-1.3 years, 66.4% female; typical
      symptoms 57.0%, 53.9% tested on therapy) underwent pH-impedance testing and
      subsequent medical therapy for reflux symptoms, and completed required
      questionnaires. On follow-up 3.35+/-0.14 years later, mean GSS declined by 45.0%,
      with 42.2% patients reporting >=50% GSS improvement. On univariate analysis,
      total AET, AET>=4.0%, and GPE for all reflux events predicted both linear and
      >=50% GSS improvement, but RET and number of reflux events did not. On
      multivariate analysis, controlling for testing on or off therapy, only AET
      (P=0.003) and GPE for all reflux events (P=0.029) predicted GSS improvement.
      CONCLUSIONS: Acid-based reflux parameters offer greater value over impedance
      based nonacid-reflux parameters in predicting symptomatic responses to proton
      pump inhibitor (PPI) therapy. Our findings support conducting pH-impedance
      studies off PPI therapy to maximize clinical utility in predicting outcome.

PMID- 24732867
TI  - Prucalopride improves bowel function and colonic transit time in patients with
      chronic constipation: an integrated analysis.
AB  - OBJECTIVES: Constipation is often characterized by slow colonic transit, but the
      relationship between colonic transit time (CTT) and symptoms is unclear. The aims
      of this study were to investigate the effect of prucalopride, a 5
      hydroxytryptamine receptor-4 agonist, on CTT and assess the relationship between
      CTT and symptoms. METHODS: This was an integrated analysis of three randomized,
      placebo-controlled, phase 2 dose-finding trials of prucalopride in patients with
      chronic constipation (ClinicalTrials.gov identifiers: NCT00617513; NCT00631813;
      and NCT00596596). Measurements of CTT were analyzed using radio-opaque markers at
      the start and end (4 or 12 weeks) of treatment. At these visits, patients
      assessed the presence and severity of their symptoms. RESULTS: In total, 280
      patients had CTT measurements before and at the end of treatment and were
      included in the analysis. Their mean age was 43 years, 93% were women, and mean
      duration of constipation was 19 years. After a once daily treatment with
      prucalopride 2 mg (n=98) and 4 mg (n=70), CTT was reduced by 12.0 h (95%
      confidence interval (CI): -18.9, -5.1) and 13.9 h (95% CI: -20.5, -7.4),
      respectively; CTT increased by 0.5 h (95% CI: -4.5, 5.5) with placebo (n=112). At
      the end of the trial, symptoms including bloating/flatulence/distension and
      straining were rated as severe or very severe by a higher proportion of patients
      with slow or very slow CTT (>48 h) than by those with normal CTT. CONCLUSIONS:
      There was a clear relationship between increased CTT and increased symptom
      severity in patients with chronic constipation. Treatment with prucalopride
      accelerated CTT in these individuals.

PMID- 24732869
TI  - Poor adherence to AASLD guidelines for chronic hepatitis B Management and
      treatment in a large academic medical center.
AB  - OBJECTIVES: Adherence to the American Association for the Study of Liver Disease
      (AASLD) guidelines for the management of chronic hepatitis B (CHB) has not been
      systematically assessed. We sought to comprehensively evaluate adherence to five
      key areas of these guidelines. We also evaluated physician and patient factors
      underlying nonadherence, and predictors of nonadherence such as physician type,
      patient demographic factors, and phase of CHB infection. METHODS: Nine hundred
      and sixty-two adult patients were retrospectively identified. Each patient chart
      was reviewed in detail. The primary outcome was adherence to five areas of the
      AASLD guidelines: (i) timely alanine aminotransferase (ALT)/hepatitis B virus DNA
      level checks needed to monitor inactive carrier and immune-tolerant phases; (ii)
      liver biopsy to guide decisions on initiating treatment; (iii) treatment
      initiation when indicated; (iv) hepatocellular carcinoma (HCC) screening; (v)
      testing for hepatitis A virus (HAV) immunity, HIV, and hepatitis C virus (HCV) co
      infections. RESULTS: Sixty percent did not undergo clinically indicated liver
      biopsies, largely owing to physician nonadherence. Eighty-nine percent of these
      missed biopsies were needed to further assess possible e-antigen-negative CHB. A
      high treatment initiation rate was found for the treatment eligible, but 121
      patients had unclear treatment eligibility as they warranted, but did not
      undergo, liver biopsy. Forty-five percent did not have timely HCC screening,
      although gastroenterology physicians had the highest odds of adherence, and 29%
      did not have timely CHB lab assessment; patients seen by gastroenterologists had
      twice the odds compared with primary care physicians of undergoing timely lab
      monitoring. Thirty-five, 24, and 54% were not tested for HAV, HCV, and HIV co
      infections. CONCLUSIONS: Our findings show remarkably poor adherence to AASLD
      guidelines, particularly in the areas of liver biopsy, timely HCC and ALT
      monitoring, and testing for co-infection. These findings call for greater efforts
      to meet physician knowledge gaps, incorporation of decision support tools, and
      improved communication among providers.

PMID- 24732870
TI  - Clinical impact and cost-effectiveness of making third-line antiretroviral
      therapy available in sub-Saharan Africa: a model-based analysis in Cote d'Ivoire.
AB  - OBJECTIVE: In sub-Saharan Africa, HIV-infected adults who fail second-line
      antiretroviral therapy (ART) often do not have access to third-line ART. We
      examined the clinical impact and cost-effectiveness of making third-line ART
      available in Cote d'Ivoire. METHODS: We used a simulation model to compare 4
      strategies after second-line ART failure: continue second-line ART (C-ART2),
      continue second-line ART with an adherence reinforcement intervention (AR-ART2),
      immediate switch to third-line ART (IS-ART3), and continue second-line ART with
      adherence reinforcement, switching patients with persistent failure to third-line
      ART (AR-ART3). Third-line ART consisted of a boosted-darunavir plus raltegravir
      based regimen. Primary outcomes were 10-year survival and lifetime incremental
      cost-effectiveness ratios (ICERs), in $/year of life saved (YLS). ICERs below
      $3585 (3 times the country per capita gross domestic product) were considered
      cost-effective. RESULTS: Ten-year survival was 6.0% with C-ART2, 17.0% with AR
      ART2, 35.4% with IS-ART3, and 37.2% with AR-ART3. AR-ART2 was cost-effective
      ($1100/YLS). AR-ART3 had an ICER of $3600/YLS and became cost-effective if the
      cost of third-line ART decreased by <1%. IS-ART3 was less effective and more
      costly than AR-ART3. Results were robust to wide variations in the efficacy of
      third-line ART and of the adherence reinforcement, as well as in the cost of
      second-line ART. CONCLUSIONS: Access to third-line ART combined with an intense
      adherence reinforcement phase, used as a tool to distinguish between patients who
      can still benefit from their current second-line regimen and those who truly need
      third-line ART would provide substantial survival benefits. With minor decreases
      in drug costs, this strategy would be cost-effective.

PMID- 24732871
TI  - Peripheral neuropathy in primary HIV infection associates with systemic and
      central nervous system immune activation.
AB  - BACKGROUND: Peripheral neuropathy (PN) is a frequent complication of chronic HIV
      infection. We prospectively studied individuals with primary HIV infection (<1
      year after transmission) to assess the presence of and laboratory associations
      with PN in this early stage. METHODS: Standardized examination and analysis of
      blood and cerebrospinal fluid (CSF) was performed in participants with laboratory
      confirmed primary HIV infection. PN was defined as >=1 of the following
      unilateral or bilateral signs: decreased distal limb position, vibration, or
      temperature sense or hyporeflexia; symptomatic PN (SPN) was defined as the
      presence of these signs with symptoms. Analysis used nonparametric statistics.
      RESULTS: Overall, 20 (35%) of 58 antiretroviral-naive male subjects without
      diabetes evaluated at a median of 107 days post HIV transmission met criteria for
      PN. Thirteen (65%) of 20 PN subjects met criteria for SPN; 6 (30%) of 20 had
      bilateral findings. PN subjects and no PN subjects (NPN) did not differ in median
      age, days post HIV transmission, blood CD4 or CD8 counts, CSF or plasma HIV RNA
      levels, CSF white blood cell counts, or CSF to blood albumin ratio. PN and SPN
      subjects had elevated CSF neopterin (P = 0.003 and P = 0.0005), CSF monocyte
      chemoattractant protein-1 (P = 0.006 and P = 0.01), and blood neopterin (P =
      0.006 and P = 0.009) compared with NPN subjects. PN subjects had a higher
      percentage of activated phenotype CSF CD8 T lymphocytes than NPN subjects (P =
      0.009). CONCLUSIONS: Signs of PN were detected by detailed neurologic examination
      in 35% of men enrolled in a neurological study at a median of 3.5 months after
      HIV transmission. PN during this early period may be mediated by systemic and
      nervous system immune responses to HIV.

PMID- 24732872
TI  - Prevalence, treatment, and control of dyslipidemia and hypertension in 4278 HIV
      outpatients.
AB  - OBJECTIVE: Patients with HIV may have an increased risk of cardiovascular disease
      (CVD). The objective of this study was to determine the prevalence, treatment,
      and control of low-density lipoprotein cholesterol (LDL-C) dyslipidemia and
      hypertension in a population of HIV-infected patients at an HIV/AIDS clinic in
      New York City. METHODS: Review of electronic medical records of 4278 HIV-infected
      patients aged 20 years or older in a racially and ethnically diverse urban
      HIV/AIDS clinic based in a large tertiary hospital and designated New York State
      AIDS Center that provides comprehensive care. LDL-C dyslipidemia was defined
      according to the National Cholesterol Education Program Adult Treatment Panel III
      goals and hypertension according to Joint National Committee VII criteria.
      RESULTS: The prevalence of LDL-C dyslipidemia was 35%. Ninety percent of patients
      with LDL-C dyslipidemia were treated and 75% of those treated were at goal.
      Patients in high-risk groups (56%), including known coronary heart disease (57%)
      or coronary heart disease equivalents (62%), were less likely to be at LDL-C
      goal. The prevalence of hypertension was 43%. Seventy-five percent of patients
      with hypertension were treated but only 57% overall were at goal. CONCLUSIONS:
      Although most patients with HIV and LDL-C dyslipidemia or hypertension are
      treated, a significant percentage did not have adequate control of these risk
      factors. As patients with HIV are at higher risk for CVD and living to an age
      where CVD is more common, it will be important to identify ways to better manage
      and control CVD risk factors in this patient population. A comprehensive care
      model such as our setting may serve as an option.

PMID- 24732873
TI  - Detection of HIV-1 matrix protein p17 quasispecies variants in plasma of chronic
      HIV-1-infected patients by ultra-deep pyrosequencing.
AB  - BACKGROUND: The HIV-1 matrix protein p17 (p17MA) is a pleiotropic protein that
      plays a key role in the HIV-1 life cycle. It has been long believed to have a
      highly conserved primary amino acid sequence and a well-preserved structural
      integrity to avoid severe fitness consequences. However, recent data revealed
      that the carboxy (COOH)-terminus of p17MA possesses high levels of predicted
      intrinsic disorder, which would subtend to at least partially unfolded status of
      this region. This finding pointed to the need of investigating p17MA
      heterogeneity. METHODS: The degree of intrapatient variations in the p17MA
      primary sequence was assessed on plasma viral RNA by using ultra-deep
      pyrosequencing. RESULTS: Data obtained support a complex nature of p17MA
      quasispecies, with variants present at variable frequency virtually in all
      patients. Clusters of mutations were scattered along the entire sequence of the
      viral protein, but they were more frequently detected within the COOH-terminal
      region of p17MA. Moreover, deletions and insertions also occurred in a restricted
      area of the COOH-terminal region. CONCLUSIONS: On the whole, our data show that
      the intrapatient level of sequence diversity in the p17MA is much higher than
      predicted before. Our results pave the way for further studies aimed at
      unraveling possible correlations between the presence of distinct p17MA variants
      and peculiar clinical evolutions of HIV-1 disease. The presence of p17MA
      quasispecies diversity may offer new tools to improve our understanding of the
      viral adaptation during the natural history of HIV-1 infection.

PMID- 24732874
TI  - Increased left ventricular posterior wall end-diastolic thickness in adolescents
      with delayed diagnosis of vertically acquired HIV infection.

PMID- 24732875
TI  - Functionally defective high-density lipoproteins are related to heightened T-cell
      activation in vertically HIV-infected adolescents.
AB  - We assessed high-density lipoprotein (HDL) anti-inflammatory properties in a
      cohort of vertically HIV-infected adolescents. We hypothesized that
      proatherogenic mechanisms related to inflammation and immune activation during
      HIV infection may impair HDL functionality and impact on the atherosclerotic
      burden. Compared with healthy controls, HDL from HIV-infected adolescents
      presented impaired functionality, as determined by its ability to inhibit
      monocyte chemotaxis in vitro, which correlated with detectable viral loads (P =
      0.044), lower CD4 nadir (P = 0.043), increased levels of CD4 T-cell activation (P
      = 0.018), higher C-reactive protein (P = 0.009), and a tendency toward thicker
      carotid intima-media thickness (P = 0.071).

PMID- 24732876
TI  - Altered innate immune development in HIV-exposed uninfected infants.
AB  - BACKGROUND: Early in life, HIV-exposed uninfected (HEU) infants are at an
      increased risk of morbidity and mortality from infectious disease compared with
      HIV-unexposed (UE) infants. To improve our understanding of the mechanisms
      underlying their increased risk, we contrasted innate immune development between
      HEU and UE infants in a developing world setting, where early life infectious
      disease risk is exceptionally high. METHODS: A prospective longitudinal cohort of
      HEU and UE newborns was established, and the most detailed characterization to
      date of HEU infant immune development was performed. Single-cell cytokine
      production was analyzed by flow cytometry after stimulation of whole blood with
      pathogen-associated molecular patterns (PAMPs). RESULTS: Monocyte, classical
      dendritic cell, and plasmacytoid dendritic cell composition was similar between
      HEU and UE infants throughout the first year of life. However, HEU mononuclear
      cells mounted an enhanced pro-inflammatory response to PAMP stimulation, both in
      quantity of cytokine produced per cell and in proportion of responder cells.
      Significant differences in cytokine production were detected on the single-cell
      level in a PAMP-specific pattern, but only at 2 and 6 weeks of age; all
      differences normalized by 12 months of age. CONCLUSIONS: This time course of
      innate immune deviation early in life corresponds to the clinical window of
      vulnerability to infections in HEU infants and may be at least partially
      responsible for their increased morbidity and mortality from infectious disease.

PMID- 24732877
TI  - Spontaneous control of HIV replication, but not HAART-induced viral suppression,
      is associated with lower activation of immune cells.
AB  - HIV replication control is important to reduce AIDS progression. We determined
      frequency and activation status of immune cells in spontaneous HIV controllers
      vs. individuals with highly active antiretroviral therapy (HAART)-controlled
      viral load. HIV controllers exhibited significantly higher frequency of CD4 T
      cells and myeloid dendritic cells compared with HAART-controlled viral load.
      Additionally, HIV controllers have a significantly lower percentage of cells
      expressing activation markers on CD4 and CD8 T cells, myeloid dendritic cells,
      and natural killer cells. These findings suggest that during HIV infection,
      conservation of a normal frequency and physiological range of immune activation
      is associated with spontaneous, but not HAART-induced, control of viral
      replication.

PMID- 24732878
TI  - Cocaine alters cytokine profiles in HIV-1-infected African American individuals
      in the DrexelMed HIV/AIDS genetic analysis cohort.
AB  - BACKGROUND: This study evaluated the relationship between illicit drug use and
      HIV-1 disease severity in HIV-1-infected patients enrolled in the DREXELMED
      HIV/AIDS Genetic Analysis Cohort. Because cocaine is known to have
      immunomodulatory effects, the cytokine profiles of preferential nonusers, cocaine
      users, and multidrug users were analyzed to understand the effects of cocaine on
      cytokine modulation and HIV-1 disease severity. METHODS: Patients within the
      cohort were assessed approximately every 6 months for HIV-1 clinical markers and
      for history of illicit drug, alcohol, and tobacco use. The Luminex human cytokine
      30-plex panel was used for cytokine quantitation. Analysis was performed using a
      newly developed biostatistical model. RESULTS: Substance abuse was common within
      the cohort. Using the drug screens at the time of each visit, the subjects in the
      cohort were categorized as preferential nonusers, cocaine users, or multidrug
      users. The overall health of the nonuser population was better than that of the
      cocaine users, with peak and current viral loads in nonusers substantially lower
      than those in cocaine and multidrug users. Among the 30 cytokines investigated,
      differential levels were established within the 3 populations. The T-helper 2
      cytokines, interleukin-4 and -10, known to play a critical role during HIV-1
      infection, were positively associated with increasing cocaine use. Clinical
      parameters such as latest viral load, CD4 T-cell counts, and CD4:CD8 ratio were
      also significantly associated with cocaine use, depending on the statistical
      model used. CONCLUSIONS: Based on these assessments, cocaine use seems to be
      associated with more severe HIV-1 disease.

PMID- 24732879
TI  - 8-oxoguanine causes spontaneous de novo germline mutations in mice.
AB  - Spontaneous germline mutations generate genetic diversity in populations of
      sexually reproductive organisms, and are thus regarded as a driving force of
      evolution. However, the cause and mechanism remain unclear. 8-oxoguanine (8-oxoG)
      is a candidate molecule that causes germline mutations, because it makes DNA more
      prone to mutation and is constantly generated by reactive oxygen species in vivo.
      We show here that endogenous 8-oxoG caused de novo spontaneous and heritable G to
      T mutations in mice, which occurred at different stages in the germ cell lineage
      and were distributed throughout the chromosomes. Using exome analyses covering
      40.9 Mb of mouse transcribed regions, we found increased frequencies of G to T
      mutations at a rate of 2 * 10(-7) mutations/base/generation in offspring of
      Mth1/Ogg1/Mutyh triple knockout (TOY-KO) mice, which accumulate 8-oxoG in the
      nuclear DNA of gonadal cells. The roles of MTH1, OGG1, and MUTYH are specific for
      the prevention of 8-oxoG-induced mutation, and 99% of the mutations observed in
      TOY-KO mice were G to T transversions caused by 8-oxoG; therefore, we concluded
      that 8-oxoG is a causative molecule for spontaneous and inheritable mutations of
      the germ lineage cells.

PMID- 24732881
TI  - Nonlinear excitations match correlated motions unveiled by NMR in proteins: a new
      perspective on allosteric cross-talk.
AB  - In this paper we propose a novel theoretical framework for interpreting long
      range dynamical correlations unveiled in proteins through NMR measurements. The
      theoretical rationale relies on the hypothesis that correlated motions in
      proteins may be reconstructed as large-scale, collective modes sustained by long
      lived nonlinear vibrations known as discrete breathers (DB) localized at key, hot
      spot sites. DBs are spatially localized modes, whose nonlinear nature hinders
      resonant coupling with the normal modes, thus conferring them long lifetimes as
      compared to normal modes. DBs have been predicted to exist in proteins, localized
      at few hot-spot residues typically within the stiffest portions of the structure.
      We compute DB modes analytically in the framework of the nonlinear network model,
      showing that the displacement patterns of many DBs localized at key sites match
      to a remarkable extent the experimentally uncovered correlation blueprint. The
      computed dispersion relations prove that it is physically possible for some of
      these DBs to be excited out of thermal fluctuations at room temperature. Based on
      our calculations, we speculate that transient energy redistribution among the
      vibrational modes in a protein might favor the emergence of DB-like bursts of
      long-lived energy at hot-spot sites with lifetimes in the ns range, able to
      sustain critical, function-encoding correlated motions. More generally, our
      calculations provide a novel quantitative tool to predict fold-spanning dynamical
      pathways of correlated residues that may be central to allosteric cross-talk in
      proteins. 

PMID- 24732880
TI  - Transient receptor potential vanilloid type 1 channel may modulate opioid reward.
AB  - Transient receptor potential vanilloid type 1 (TRPV1), a nonselective cation
      channel, is a well-known pain-related receptor. TRPV1 involvement in morphine
      induced antinociception, tolerance, and withdrawal symptoms has been previously
      reported. Emerging evidence indicates that TRPV1 may be related to both the
      cellular and behavioral effects of addictive drugs. In the present study, we
      investigated the role of TRPV1 in morphine reward using the conditioned place
      preference (CPP) paradigm in mice. Repeated morphine treatments upregulated TRPV1
      expression in the dorsal striatum (DSt). Treatment with a TRPV1 agonist
      potentiated morphine reward, and pretreatment with TRPV1 antagonists attenuated
      these effects. Microinjection of a selective TRPV1 antagonist into the DSt
      significantly inhibited morphine-CPP. In addition, treatment with a TRPV1
      antagonist suppressed morphine-induced increases in MU-opioid receptor binding,
      adenylyl cyclase 1 (AC1), p38 mitogen-activated protein kinase (p38 MAPK), and
      nuclear factor kappa B (NF-kappaB) expression in the DSt. Administering a p38
      inhibitor not only prevented morphine-CPP, but also prevented morphine-induced NF
      kappaB and TRPV1 activation in the DSt. Furthermore, injecting an NF-kappaB
      inhibitor significantly blocked morphine-CPP. Our findings suggest that TRPV1 in
      the DSt contribute to morphine reward via AC1, p38 MAPK, and NF-kappaB. Brain
      TRPV1 may serve as a novel therapeutic target to treat morphine-addictive
      disorders. 

PMID- 24732882
TI  - Expression of bone morphogenetic protein-6 in dental follicle stem cells and its
      effect on osteogenic differentiation.
AB  - The dental follicle (DF) plays an essential role in tooth eruption via regulation
      of bone resorption and bone formation. Bone morphogenetic protein-6 (BMP6)
      expression in the DF is coincident with bone growth in the tooth crypt. DF stem
      cells (DFSCs) have been shown to possess strong osteogenic capability. This study
      aims to determine the expression of BMP6 in DFSCs and to elucidate the role of
      BMP6 in the osteogenesis of DFSCs. DFSCs and their non-stem cell counterpart, DF
      cells (DFCs), were obtained from the DFs of rat pups. We showed that expression
      of BMP6 was significantly higher in the DFSCs than in the DFCs. DFSCs lost
      osteogenic capability during in vitro expansion, and DFSCs in late passages had
      reduced BMP6 expression as compared to early passages of DFSCs when they were
      subjected to osteogenic induction. Addition of exogenous human recombinant BMP6
      (hrBMP6) to the osteogenic medium dramatically enhanced the osteogenesis of the
      late-passage DFSCs. Knockdown of BMP6 by short interfering RNA in the DFSCs in
      early passages resulted in a decrease in osteogenesis, which could be restored by
      addition of hrBMP6. We concluded that DFSCs need to express high levels of BMP6
      to maintain their osteogenesis capability. Increased BMP6 expression seen in vivo
      in the DF may reflect the activation of DFSCs for osteogenic differentiation for
      bone growth during tooth eruption.

PMID- 24732883
TI  - Spatial and temporal analysis of Air Pollution Index and its timescale-dependent
      relationship with meteorological factors in Guangzhou, China, 2001-2011.
AB  - There is an increasing interest in spatial and temporal variation of air
      pollution and its association with weather conditions. We presented the spatial
      and temporal variation of Air Pollution Index (API) and examined the associations
      between API and meteorological factors during 2001-2011 in Guangzhou, China. A
      Seasonal-Trend Decomposition Procedure Based on Loess (STL) was used to decompose
      API. Wavelet analyses were performed to examine the relationships between API and
      several meteorological factors. Air quality has improved since 2005. APIs were
      highly correlated among five monitoring stations, and there were substantial
      temporal variations. Timescale-dependent relationships were found between API and
      a variety of meteorological factors. Temperature, relative humidity,
      precipitation and wind speed were negatively correlated with API, while diurnal
      temperature range and atmospheric pressure were positively correlated with API in
      the annual cycle. Our findings should be taken into account when determining air
      quality forecasts and pollution control measures. 

PMID- 24732884
TI  - Assessing the relationship and influence of black carbon on distribution status
      of organochlorines in the coastal sediments from Pakistan.
AB  - Levels of total organic carbon (TOC) and black carbon (BC) were determined
      together with those of organochlorine pesticides (OCPs) and polychlorinated
      biphenyls (PCBs) in the selected eighteen coastal sites (n = 285) along the
      Arabian Sea from Pakistan. Results showed that the total concentration of TOC,
      BC, ?OCPs and ?26PCBs ranged between 0.3 and 2.9% dw, 0.1-0.2% dw, 0.9-110 ng g(
      1) dw and 6.2-1200 ng g(-1) dw, respectively. Correlation analysis of BC (r =
      0.26-0.89) and TOC (r = 0.06-0.69) revealed a stronger association with studied
      compounds. The sedimentary depositional fluxes (D) for ?OCPs and ?26PCBs were
      calculated as 1.7 and 4.9 tons yr(-1), respectively. In the coastal belt of
      Pakistan, sedimentary mass inventories (I) indicated the presence of 13 and 37
      metric tons of ?OCPs and ?26PCBs, respectively. 

PMID- 24732885
TI  - Decomposing the profile of PM in two low polluted German cities--mapping of air
      mass residence time, focusing on potential long range transport impacts.
AB  - This paper aims to decompose the profile of particulates in Karlsruhe and Potsdam
      (Germany), focusing on the localization of PM potential transboundary sources. An
      air mass cluster analysis was implemented, followed by a study of air mass
      residence time on a grid of a 0.5 degrees  * 0.5 degrees  resolution.
      Particulate/gaseous daily air pollution and meteorological data were used to
      indicate PM local sources. Four Principal Component Analysis (PCA) components
      were produced: traffic, photochemical, industrial/domestic and particulate.
      PM2.5/PM10 ratio seasonal trends, indicated production of PMCOARSE (PM10-PM2.5)
      from secondary sources in Potsdam during warm period (WP). The residing areas of
      incoming slow moving air masses are potential transboundary PM sources. For
      Karlsruhe those areas were mainly around the city. An air mass residence time
      secondary peak was observed over Stuttgart. For Potsdam, areas with increased
      dwelling time of the arriving air parcels were detected particularly above E/SE
      Germany. 

PMID- 24732886
TI  - Endothelial apoptosis in pulmonary hypertension is controlled by a
      microRNA/programmed cell death 4/caspase-3 axis.
AB  - Pulmonary endothelial cell apoptosis is a transient, yet defining pathogenic
      event integral to the onset of many pulmonary vascular diseases such as pulmonary
      hypertension (PH). However, there is a paucity of information concerning the
      molecular pathway(s) that control pulmonary arterial endothelial cell apoptosis.
      Here, we introduce a molecular axis that when functionally active seems to induce
      pulmonary arterial endothelial cell apoptosis in vitro and PH in vivo. In
      response to apoptotic stimuli, human pulmonary arterial endothelial cells
      exhibited robust induction of a programmed cell death 4 (PDCD4)/caspase
      3/apoptotic pathway that was reversible by direct PDCD4 silencing. Indirectly,
      this pathway was also repressed by delivery of a microRNA-21 mimic. In vivo,
      genetic deletion of microRNA-21 in mice (miR-21(-/-) mice) resulted in functional
      activation of the PDCD4/caspase-3 axis in the pulmonary tissues, leading to the
      onset of progressive PH. Conversely, microRNA-21-overexpressing mice (CAG
      microRNA-21 mice) exhibited reduced PDCD4 expression in pulmonary tissues and
      were partially resistant to PH in response to chronic hypoxia plus SU 5416
      injury. Furthermore, direct PDCD4 knockout in mice (PDCD4(-/-) mice) potently
      blocked pulmonary caspase-3 activation and the development of chronic hypoxia
      plus SU 5416 PH, confirming its importance in disease onset. Broadly, these
      findings support the existence of a microRNA-21-responsive PDCD4/caspase-3
      pathway in the pulmonary tissues that when active serves to promote endothelial
      apoptosis in vitro and PH in vivo. 

PMID- 24732887
TI  - Interferon regulatory factor 1 is required for cardiac remodeling in response to
      pressure overload.
AB  - Interferon regulatory factor 1 (IRF1), a critical member of the IRF family, was
      previously shown to be associated with the immune system and to be involved in
      apoptosis and tumor suppression. However, the role of IRF1 in pressure overload
      induced cardiac remodeling has remained unclear. Using genetic approaches, we
      established a central role for the IRF1 transcription factor in the regulation of
      cardiac remodeling both in vivo and in vitro, and we determined the mechanism
      underlying this process. The expression level of IRF1 was remarkably altered in
      both failing human hearts and hypertrophic murine hearts. Transgenic mice with
      cardiac-specific IRF1 overexpression exacerbated aortic banding-induced cardiac
      hypertrophy, ventricular dilation, fibrosis, and dysfunction, whereas IRF1
      deficient (knockout) mice exhibited a significant reduction in the hypertrophic
      response. Similar results were observed in a global IRF1-knockout rat model.
      Mechanistically, the prohypertrophic effects elicited by IRF1 in response to
      pathological stimuli were associated with the direct activation of inducible
      nitric oxide synthase (iNOS). Furthermore, we identified 1 IRF1-binding site in
      the promoter region of the iNOS gene, which was essential for its transcription.
      To examine the IRF1-iNOS axis in vivo, we generated IRF1-transgenic/iNOS-knockout
      mice. IRF1 exerted profoundly detrimental effects in these mice; however, these
      effects were nullified by iNOS ablation. These data suggest the IRF1-iNOS axis as
      a crucial regulator of cardiac remodeling and that IRF1 could be a potent
      therapeutic target for cardiac remodeling. 

PMID- 24732888
TI  - Renal denervation: what next?

PMID- 24732889
TI  - Estrogen protects against intracranial aneurysm rupture in ovariectomized mice.
AB  - Clinical observations suggest that postmenopausal women have a higher incidence
      of aneurysmal rupture than premenopausal women. We hypothesize that a relative
      deficiency in estrogen may increase the risks of aneurysmal growth and
      subarachnoid hemorrhage in postmenopausal women. We assessed the effects of
      estrogen and selective estrogen receptor subtype agonists on the development of
      aneurysmal rupture in ovariectomized female mice. We used an intracranial
      aneurysm mouse model that recapitulates the key features of human intracranial
      aneurysms, including spontaneous rupture. Ten- to 12-week-old ovariectomized
      female mice received treatment with estrogen, nonselective estrogen receptor
      antagonist, estrogen receptor-alpha agonist, or estrogen receptor-beta agonist
      starting 6 days after aneurysm induction so that the treatments affected the
      development of aneurysmal rupture without affecting aneurysmal formation.
      Estrogen significantly reduced the incidence of ruptured aneurysms and rupture
      rates in ovariectomized mice. Nonselective estrogen receptor antagonist abolished
      the protective effect of estrogen. Although estrogen receptor-alpha agonist did
      not affect the incidence of ruptured aneurysms or rupture rates, estrogen
      receptor-beta agonist prevented aneurysmal rupture without affecting the
      formation of aneurysms. The protective role of estrogen receptor-beta agonist was
      abolished by the inhibition of nitric oxide synthase. We showed that estrogen
      prevented aneurysmal rupture in ovariectomized female mice. The protective effect
      of estrogen seemed to occur through the activation of estrogen receptor-beta, a
      predominant subtype of estrogen receptor in human intracranial aneurysms and
      cerebral arteries. 

PMID- 24732890
TI  - Association between urinary sodium, creatinine, albumin, and long-term survival
      in chronic kidney disease.
AB  - Dietary sodium intake is associated with hypertension and cardiovascular risk in
      the general population. In patients with chronic kidney disease, sodium intake
      has been associated with progressive renal disease, but not independently of
      proteinuria. We studied the relationship between urinary sodium (UNa) excretion
      and UNa to creatinine ratio and mortality or requirement for renal replacement
      therapy in chronic kidney disease. Adult patients attending a renal clinic who
      had >=1 24-hour UNa measurement were identified. Twenty-four-hour UNa measures
      were collected and UNa to creatinine ratio calculated. Time to renal replacement
      therapy or death was recorded. Four hundred twenty-three patients were identified
      with mean estimated glomerular filtration rate of 48 mL/min per 1.73 m(2). Ninety
      patients required renal replacement therapy and 102 patients died. Mean slope
      decline in estimated glomerular filtration rate was -2.8 mL/min per 1.73 m(2) per
      year. Median follow-up was 8.5 years. Patients who died or required renal
      replacement therapy had significantly higher UNa excretion and UNa to creatinine
      ratio, but the association with these parameters and poor outcome was not
      independent of renal function, age, and albuminuria. When stratified by
      albuminuria, UNa to creatinine ratio was a significant cumulative additional risk
      for mortality, even in patients with low-level albuminuria. There was no
      association between low UNa and risk, as observed in some studies. This study
      demonstrates an association between UNa excretion and mortality in chronic kidney
      disease, with a cumulative relationship between sodium excretion, albuminuria,
      and reduced survival. These data support reducing dietary sodium intake in
      chronic kidney disease, but additional study is required to determine the target
      sodium intake. 

PMID- 24732891
TI  - Sustained sympathetic and blood pressure reduction 1 year after renal denervation
      in patients with resistant hypertension.
AB  - Renal denervation (RDN) reduces muscle sympathetic nerve activity (MSNA) and
      blood pressure (BP) in resistant hypertension. Although a persistent BP-lowering
      effect has been demonstrated, the long-term effect on MSNA remains elusive. We
      investigated whether RDN influences MSNA over time. Office BP and MSNA were
      obtained at baseline, 3, 6, and 12 months after RDN in 35 patients with resistant
      hypertension. Office BP averaged 166+/-22/88+/-19 mm Hg, despite the use of an
      average of 4.8+/-2.1 antihypertensive drugs. Baseline MSNA was 51+/-11 bursts/min
      ~2- to 3-fold higher than the level observed in healthy controls. Mean office
      systolic and diastolic BP significantly decreased by -12.6+/-18.3/-6.5+/-9.2, 
      16.1+/-25.6/-8.6+/-12.9, and -21.2+/-29.1/-11.1+/-12.9 mm Hg (P<0.001 for both
      systolic BP and diastolic BP) with RDN at 3-, 6-, and 12-month follow-up,
      respectively. MSNA was reduced by -8+/-12, -6+/-12, and -6+/-11 bursts/min
      (P<0.01) at 3-, 6-, and 12-month follow-up. The reduction in MSNA was maintained,
      despite a progressive fall in BP over time. No such changes were observed in 7
      control subjects at 6-month follow-up. These findings confirm previous reports on
      the favorable effects of RDN on elevated BP and demonstrate sustained reduction
      of central sympathetic outflow <=1-year follow-up in patients with resistant
      hypertension and high baseline MSNA. These observations are compatible with the
      hypothesis of a substantial contribution of afferent renal nerve signaling to
      increased BP in resistant hypertension and argue against a relevant reinnervation
      at 1 year after procedure. 

PMID- 24732892
TI  - Effects of cardiac overexpression of the angiotensin II type 2 receptor on
      remodeling and dysfunction in mice post-myocardial infarction.
AB  - The activation of angiotensin II type 2 receptor (AT2R) has been considered
      cardioprotective. However, there are controversial findings regarding the role of
      overexpressing AT2R in the heart. Using transgenic mice with different levels of
      AT2R gene overexpression in the heart (1, 4, or 9 copies of the AT2R transgene:
      Tg1, Tg4, or Tg9), we studied the effect of AT2R overexpression on left
      ventricular remodeling and dysfunction post-myocardial infarction (MI). Tg1, Tg4,
      Tg9, and their wild-type littermates were divided into (1) sham MI, (2) MI plus
      vehicle, and (3) MI plus AT2R antagonist. Treatments were started 4 weeks after
      MI and continued for 8 weeks. AT2R protein and mRNA expression in the heart was
      significantly increased in transgenic mice, and the increase positively
      correlated with copies of the transgene. AT1R protein and mRNA expression
      remained unchanged in Tg1 and Tg4 but slightly increased in Tg9 mice. Systolic
      blood pressure and cardiac phenotypes did not differ among strains under basal
      conditions. MI caused myocardial hypertrophy, interstitial fibrosis, ventricular
      dilatation, and dysfunction associated with increased protein expression of Nox2
      and transforming growth factor beta1. These pathological responses were
      diminished in Tg1 and Tg4 mice. Moreover, the protective effects of AT2R were
      abolished by AT2R antagonist and also absent in Tg9 mice. We thus conclude that
      whether overexpression of AT2R is beneficial or detrimental to the heart is
      largely dependent on expression levels and possibly via regulations of Nox2 and
      transforming growth factor beta1 signaling pathways.

PMID- 24732893
TI  - Matrix rigidity-modulated cardiovascular organoid formation from embryoid bodies.
AB  - Stem cell clusters, such as embryoid bodies (EBs) derived from embryonic stem
      cells, are extensively studied for creation of multicellular clusters and complex
      functional tissues. It is common to control phenotypes of ES cells with varying
      molecular compounds; however, there is still a need to improve the
      controllability of cell differentiation, and thus, the quality of created tissue.
      This study demonstrates a simple but effective strategy to promote formation of
      vascularized cardiac muscle-like tissue in EBs and form contracting
      cardiovascular organoids by modulating the stiffness of a cell adherent hydrogel.
      Using collagen-conjugated polyacrylamide hydrogels with controlled elastic
      moduli, we discovered that cellular organization in a form of vascularized
      cardiac muscle sheet was maximal on the gel with the stiffness similar to cardiac
      muscle. We envisage that the results of this study will greatly contribute to
      better understanding of emergent behavior of stem cells in developmental and
      regeneration process and will also expedite translation of EB studies to drug
      screening device assembly and clinical treatments.

PMID- 24732894
TI  - Argatroban for preventing occlusion and restenosis after extracranial artery
      stenting.
AB  - BACKGROUND/AIMS: Restenosis following extracranial artery stenting is a
      limitation that affects long-term outcomes. Effective and satisfying
      pharmacological strategies in preventing restenosis have not been established.
      This study aimed to evaluate whether argatroban, a direct thrombin inhibitor,
      could reduce the risk of in-stent restenosis after extracranial artery stenting.
      METHODS: One hundred and fourteen patients hospitalized between August 2010 and
      August 2011 were enrolled. Patients were randomly assigned to argatroban (n = 58)
      and blank control groups (n = 56). The patients in the argatroban arm were
      treated with 10 mg of intravenous argatroban twice daily 2 days before and 3 days
      after the stenting procedures. Patients were followed for 12 months after the
      procedure. During follow-up, restenosis and target revascularization were
      analyzed. Recurrent cerebrovascular and cardiovascular events and deaths were
      also compared between the groups. RESULTS: One patient in the stenting group
      withdrew immediately after the procedure due to unsuccessful stenting. Restenosis
      occurred in 4 patients (7.4%) in the argatroban group and in 11 patients (21.6%)
      in the control group during the 6- to 9-month angiographic follow-up period (p =
      0.032). Nine months after the procedures, argatroban-treated patients had a trend
      towards a lower incidence of target revascularization compared with the controls
      (5.4 vs. 13.7%, p = 0.188). No major bleeding events or other adverse events
      occurred in the argatroban group. CONCLUSION: This pilot clinical trial is the
      first that uses argatroban to prevent restenosis in ischemic cerebrovascular
      disease, and suggests that intravenous administration of argatroban is effective
      and safe in preventing restenosis after extracranial artery stenting. Larger
      randomized controlled clinical trials are warranted.

PMID- 24732895
TI  - Impulsive choice predicts poor working memory in male rats.
AB  - A number of maladaptive behaviors and poor health outcomes (e.g., substance
      abuse, obesity) correlate with impulsive choice, which describes the tendency to
      prefer smaller, immediate rewards in lieu of larger, delayed rewards. Working
      memory deficits are often reported in those diagnosed with the same maladaptive
      behaviors. Human studies suggest that impulsive choice is associated with working
      memory ability but, to date, only one study has explored the association between
      working memory and impulsive choice in rats and no relation was reported. The
      current study reevaluated the association between working memory and impulsive
      choice in 19 male Long-Evans rats. Psychophysical adjusting procedures were used
      to quantify working memory (titrating-delay match-to-position procedure) and
      impulsive choice (adjusting delay procedure). Rats were partitioned into low- and
      high-impulsive groups based on performance in the impulsive choice task. Low
      impulsive rats performed significantly better in the working memory assessment.
      Across all rats, impulsive choice was negatively correlated with working memory
      performance. These findings support the hypothesis that prefrontal cortex
      function, specifically, working memory, is related to impulsive choice. Future
      research might profitably examine the experimental variables designed to
      influence working memory to evaluate the effects of these variables on impulsive
      choice and maladaptive behaviors with which it is correlated. 

PMID- 24732898
TI  - The economic burden of posttransplant events in renal transplant recipients in
      Europe.
AB  - BACKGROUND: This study aims to describe the healthcare resource utilization and
      costs of managing renal posttransplant patients over 3 years posttransplant in
      nine European countries and to stratify them by year 1 glomerular filtration rate
      (GFR). METHODS: A retrospective observational and database analysis of renal
      transplant patients and a physician questionnaire study were conducted to collect
      recipient and donor characteristics, posttransplant events, and healthcare
      resource utilization related to these posttransplant events. In each country,
      local published costs were applied to the resource use identified. The results
      were stratified by the patient GFR reading at a time point 1 year after renal
      transplant. RESULTS: The database study identified 3,181 patients who met the
      inclusion criteria, along with 2,818 transplants carried out in the centers
      surveyed by questionnaire. Total 3-year costs derived from the questionnaire
      analysis vary depending on local treatment practices, from a minimum of
      &OV0556;33,602 per patient in the Czech Republic to &OV0556;77,461 per patient in
      the Netherlands. Consistently across countries, estimated costs appear to
      decrease with improved graft functioning status (increased GFR) at 1 year. The
      average 3-year costs, discounting immunosuppression therapy and certain
      posttransplant events, per patient with a GFR greater than or equal to 60 at 1
      year are estimated to be around 35% lower than those with 15<=GFR<30. CONCLUSION:
      This study demonstrates that in Europe, worsening posttransplant renal function
      may contribute to substantive increases in resource use, with some variation
      across regions. Therefore, management strategies that promote renal function
      after transplantation have the potential to provide important resource savings.

PMID- 24732899
TI  - Liver transplantation for patient with pretransplant undetectable hepatitis C
      RNA: can eradication of virus guarantee superior outcome?

PMID- 24732900
TI  - HCV therapy with daclatasvir, PEG-IFN, and RBV after boceprevir-based therapy
      failure post-liver transplantation in hyper-IgM syndrome.

PMID- 24732901
TI  - Increasing capacity for skin surveillance in a transplant review clinic.

PMID- 24732902
TI  - A novel biomarker of immune function and initial experience in a transplant
      population.

PMID- 24732903
TI  - Who are the users of urban parks? A study with adults from Curitiba, Brazil.
AB  - BACKGROUND: The aim of this study was to analyze how sociodemographic
      characteristics, health, characteristics of quality of life, and perceptions of
      places are associated with park use in Curitiba, Brazil. METHODS: A cross
      sectional study with face-to-face interviews was conducted with 1461 adults who
      lived within the area of 500 m near 8 parks. The survey included questions about
      gender, age, socioeconomic status, education, marital status, body mass index,
      perceived health, number of morbidities, perception of quality of life, physical
      environment, leisure opportunities, self-satisfaction, and satisfaction with the
      park. The use of a specific park near the residence was identified as 1 of 3
      outcomes: park use versus nonuse, park use >= 1 time/wk, and park use >= 3
      times/wk. Poisson regression was used to examine associations between the
      independent variables and each level of park use. RESULTS: Overall park use
      (60.9%) and >= 1 time/wk (32.2%) and >= 3 times/wk use (16.8%) were associated
      with age and leisure opportunities. Leisure opportunities and park satisfaction
      were related to more frequent visits to these outdoor areas. CONCLUSIONS: These
      results can be used in guiding interventions that improve the quality of parks
      and other outdoor areas and offer leisure opportunities to the community.

PMID- 24732904
TI  - Polish Lymphoma Research Group Experience With Bexarotene in the Treatment of
      Cutaneous T-Cell Lymphoma.
AB  - Bexarotene, a synthetic retinoid licensed for the treatment of refractory
      cutaneous T-cell lymphoma (CTCL), has been used clinically in Poland since 2007
      in 21 patients. The objective of our retrospective, multicenter study was to
      evaluate our experience with bexarotene therapy, including efficacy, safety, and
      survival outcomes. We retrospectively identified 21 adult patients who were
      treated with bexarotene between the years 2007 and 2012. Starting dose of
      bexarotene was 300 mg/m per day. The analysis included 3 patients with early
      stage mycosis fungoides (MF), 16 patients with advanced-stage MF, and 2 patients
      with Sezary syndrome (SS). The mean duration of therapy with bexarotene was 14.5
      months. Use of bexarotene resulted in an overall response rate of 81.0%, although
      the overall mortality rate was 52.8%. In our study, early-stage CTCL responded
      better than advanced-stage CTCL (100.0% vs. 77.8%, respectively). The mean time
      to observable response was 1.8 months, and the mean duration of the response was
      16.4 months. Most significant side effects were hyperlipidemia, hypothyroidism,
      and a bleeding gastric ulcer. Based on the results of our analysis, bexarotene is
      a valuable tool in the treatment of refractory early-stage CTCL. Although a
      majority of patients initially responded to therapy, the high mortality rate in
      the advanced-stage group suggests that bexarotene does not completely resolve the
      therapeutic problems in all stages of CTCL. Patient stratification for bexarotene
      treatment may need a thorough reassessment, in that bexarotene may not be an
      effective drug in the very advanced stages of CTCL. 

PMID- 24732905
TI  - Colchicine-Induced Myopathy in a Tacrolimus-Treated Renal Transplant Recipient:
      Case Report and Literature Review.
AB  - Renal transplant recipients are prone to develop drug toxicities because of
      polypharmacy and drug-drug interactions. Colchicine is often used for the
      treatment of gout in these patients as nonsteroidal medications are
      contraindicated. In addition, patients are often on corticosteroids and frequent,
      periodic, dose escalation for gouty flare may lead to side effects. Colchicine
      induced myopathy has been very well described in the literature. Several cases of
      colchicine toxicity have been reported in cyclosporine-treated patients due to a
      drug-drug interaction. We report a 62-year-old African American renal transplant
      recipient who had been doing well on tacrolimus-based immunosuppression and was
      started on colchicine (0.6 mg twice daily) for gouty flare. A few days later, he
      was found to have a 4-fold increase in aspartate aminotransferase and an elevated
      creatine phosphokinase. Although this interaction is very well known with
      cyclosporine, it has not yet been reported in patients on tacrolimus. 

PMID- 24732906
TI  - Dramatic Response to Catumaxomab Treatment for Malign Ascites Related to Renal
      Cell Carcinoma With Sarcomotoid Differentiation.
AB  - Refractory malignant ascites (MA) is a common complication in cancer patients.
      Renal cell carcinoma (RCC) is rarely present with peritoneal ascites, which is
      commonly associated with carcinomas of the gastrointestinal and female
      reproductive tracts; including especially ovarian high-grade serous carcinoma.
      Currently, chemotherapy and paracentesis represent the most widely used methods
      to relieve the symptoms. Recently, intraperitoneal therapy with catumaxomab-a
      trifunctional hybrid antibody-has been introduced for the treatment of MA. The
      benefit of this treatment has been demonstrated in patients with distinct
      abdominal malignancies. In this case report, we present the first case of
      successful catumaxomab treatment against MA in a patient with advanced RCC with
      sarcomatoid differentiation. After the second administration of catumaxomab,
      paracentesis became no longer necessary. Catumaxomab might represent a safe
      treatment option for MA in the course of metastatic RCC with sarcomatoid
      differentiation. 

PMID- 24732907
TI  - An Interferon-Induced Digital Vasculitis-Like Syndrome: A Case Report.
AB  - This report describes a patient with chronic hepatitis C undergoing therapy with
      interferon (IFN) alpha who developed bilateral ischemia of his fingers. We
      present a 43-year-old man with a failed renal transplant and chronic hepatitis C.
      He was treated with 6 months of IFN therapy with good reduction of his viral
      load. He presented with 2 days of pain and swelling in the second digits of both
      hands. Workup for extrahepatic manifestations of hepatitis C was initiated
      including assessment for vasculitis because of cryoglobulin- and noncryoglobulin
      related causes. Extensive assessment with invasive and noninvasive vascular
      testing was performed. His workup for vasculitis did not reveal any specific
      reasons for the ischemic changes. Angiography of his fingers showed mild stenotic
      changes but no evidence of systemic vasculitis. IFN therapy was stopped and over
      several weeks his symptoms resolved. The ischemic changes were attributed to IFN
      therapy. The patient in this report is unique because although IFN has been
      historically reported to cause a variety of vascular syndromes, the reported
      experience in hepatitis C patients is small. In addition, the likelihood of
      encountering vasculitis and vasculitis-like syndromes in patients with hepatitis
      C is significant, and the increasing use of IFN in this population makes drug
      induced vascular changes an essential consideration in this subset of patients. 

PMID- 24732908
TI  - Decreased core-fucosylation contributes to malignancy in gastric cancer.
AB  - The object of the study is to identify N-glycan profiling changes associated with
      gastric cancer and explore the impact of core-fucosylation on biological
      behaviors of human gastric cancer cells. A total of 244 subjects including
      gastric cancer, gastric ulcer and healthy control were recruited. N-glycan
      profiling from serum and total proteins in gastric tissues was analyzed by DNA
      sequencer-assisted fluorophore-assisted capillary electrophoresis. The abundance
      of total core-fucosylated residues and the expression of enzymes involved in core
      fucosylation were analyzed with lectin blot, quantitative reverse transcription
      polymerase chain reaction, western blot, Immunohistochemical staining and lectin
      histochemical staining. The recombinant plasmids of GDP-fucose transporter and
      alpha-1,6-fucosyltransferase (Fut8) were constructed and transfected into gastric
      cancer cell lines BGC-823 and SGC-7901. CCK-8 and wound healing assay were used
      to assess the functional impact of core-fucosylation modulation on cell
      proliferation and migration. Characteristic serum N-glycan profiles were found in
      gastric cancer. Compared with the healthy control, a trianntenary structure
      abundance, peak 9 (NA3Fb), was increased significantly in gastric cancer, while
      the total abundance of core-fucosylated residues (sumfuc) was decreased. Core
      fucosylated structures, peak6(NA2F) and peak7(NA2FB) were deceased in gastric
      tumor tissues when compared with that in adjacent non-tumor tissues.
      Consistently, lens culinaris agglutinin (LCA)-binding proteins were decreased
      significantly in sera of gastric cancer, and protein level of Fut8 was decreased
      significantly in gastric tumor tissues compared with that in adjacent non-tumor
      tissues. Upregulation of GDP-Tr and Fut8 could inhibit proliferation, but had no
      significant influence on migration of BGC-823 and SGC-7901 cells. Core
      fucosylation is down regulated in gastric cancer. Upregulation of core
      fucosylation could inhibit proliferation of the human gastric cancer cells. 

PMID- 24732909
TI  - The efficacy of antidepressants on overall well-being and self-reported
      depression symptom severity in youth: a meta-analysis.
AB  - BACKGROUND: Recent meta-analyses of the efficacy of second-generation
      antidepressants for youth have concluded that such drugs possess a statistically
      significant advantage over placebo in terms of clinician-rated depressive
      symptoms. However, no meta-analysis has included measures of quality of life,
      global mental health, self-esteem, or autonomy. Further, prior meta-analyses have
      not included self-reports of depressive symptoms. METHODS: Studies were selected
      through searching Medline, PsycINFO, and the Cochrane Central Register for
      Controlled Trials databases as well as GlaxoSmithKline's online trial registry.
      We included self-reports of depressive symptoms and pooled measures of quality of
      life, global mental health, self-esteem, and autonomous functioning as a proxy
      for overall well-being. RESULTS: We found a nonsignificant difference between
      second-generation antidepressants and placebo in terms of self-reported
      depressive symptoms (k = 6 trials, g = 0.06, p = 0.36). Further, pooled across
      measures of quality of life, global mental health, self-esteem, and autonomy,
      antidepressants yielded no significant advantage over placebo (k = 3 trials, g =
      0.11, p = 0.13). DISCUSSION: Though limited by a small number of trials, our
      analyses suggest that antidepressants offer little to no benefit in improving
      overall well-being among depressed children and adolescents.

PMID- 24732910
TI  - The 9p21 locus is associated with coronary artery disease and cardiovascular
      events in the presence (but not in the absence) of coronary calcification.
AB  - Variants at the 9p21 locus have been associated with coronary artery disease
      (CAD); coronary artery calcification (CAC) is related to CAD and other
      cardiovascular events. To determine the association of the 9p21 locus with CAD in
      the presence and absence of CAC, 4 groups were enrolled in a case-control study,
      including 527 CAD patients without CAC, 692 CAD patients with CAC, 585
      individuals with simple CAC but no CAD, and 725 healthy controls. The rs1333049
      representing the locus was associated with CAD in the presence of CAC (odds ratio
      = 1.38 in allelic analysis, 95%CI, 1.19-1.60, P<0.001), but not in the absence of
      CAC. Additionally, rs1333049 was not associated with simple CAC or CAC
      severity/extent in CAD patients with CAC. 849 CAD patients undergoing
      revascularization (660 with CAC and 189 without CAC) were enrolled in a cohort
      study to test its association with cardiovascular events in CAD patients with and
      without CAC in a 3-year follow-up. rs1333049 was significantly associated with
      the incidence of cardiovascular events in non-target vessels in patients with CAC
      (hazard ratio = 1.44, 95%CI, 1.08-1.91, P = 0.012), but not in those without CAC.
      The variants at the 9p21 locus were related to CAD and post-revascularization
      events only in the presence of CAC, suggesting that they may confer risk of
      calcification-related coronary atherosclerosis. 

PMID- 24732911
TI  - Zinc regulates the acute phase response and serum amyloid A production in
      response to sepsis through JAK-STAT3 signaling.
AB  - Sepsis rapidly activates the host inflammatory response and acute phase response.
      Severe sepsis, complicated by multiple organ failure, is associated with
      overwhelming inflammation and high mortality. We previously observed that zinc
      (Zn) deficiency significantly increases mortality in a mouse model of
      polymicrobial sepsis due to over-activation of the inflammatory response. In
      order to identify potential mechanisms that account for Zn-responsive effects, we
      generated whole exome expression profiles from the lung tissue of septic mice
      that were maintained on Zn modified diets. Based on systems analysis, we observed
      that Zn deficiency enhances the acute phase response and particularly the JAK
      STAT3 pathway, resulting in increased serum amyloid A production. In vitro
      studies of primary hepatocytes and HepG2 cells substantiated that Zn-deficiency
      augments serum amyloid A production through up-regulation of the JAK-STAT3 and NF
      kappaB pathways. In contrast, Zn inhibited STAT3 activation through the up
      regulation of SHP1 activity. Collectively, these findings demonstrate that Zn
      deficiency enhances the acute phase response through up-regulation of the JAK
      STAT3 pathway, thereby perpetuating increased inflammation that may lead to
      increased morbidity and mortality in response to sepsis. 

PMID- 24732912
TI  - Expression of DNAJB12 or DNAJB14 causes coordinate invasion of the nucleus by
      membranes associated with a novel nuclear pore structure.
AB  - DNAJB12 and DNAJB14 are transmembrane proteins in the endoplasmic reticulum (ER)
      that serve as co-chaperones for Hsc70/Hsp70 heat shock proteins. We demonstrate
      that over-expression of DNAJB12 or DNAJB14 causes the formation of elaborate
      membranous structures within cell nuclei, which we designate DJANGOS for DNAJ
      associated nuclear globular structures. DJANGOS contain DNAJB12, DNAJB14, Hsc70
      and markers of the ER lumen and ER and nuclear membranes. Strikingly, they are
      evenly distributed underneath the nuclear envelope and are of uniform size in any
      one nucleus. DJANGOS are composed primarily of single-walled membrane tubes and
      sheets that connect to the nuclear envelope via a unique configuration of
      membranes, in which the nuclear pore complex appears anchored exclusively to the
      outer nuclear membrane, allowing both the inner and outer nuclear membranes to
      flow past the circumference of the nuclear pore complex into the nucleus. DJANGOS
      break down rapidly during cell division and reform synchronously in the daughter
      cell nuclei, demonstrating that they are dynamic structures that undergo
      coordinate formation and dissolution. Genetic studies showed that the chaperone
      activity of DNAJ/Hsc70 is required for the formation of DJANGOS. Further analysis
      of these structures will provide insight into nuclear pore formation and
      function, activities of molecular chaperones, and mechanisms that maintain
      membrane identity. 

PMID- 24732913
TI  - Protein abundance changes and ubiquitylation targets identified after inhibition
      of the proteasome with syringolin A.
AB  - As proteins are the main effectors inside cells, their levels need to be tightly
      regulated. This is partly achieved by specific protein degradation via the
      Ubiquitin-26S proteasome system (UPS). In plants, an exceptionally high number of
      proteins are involved in Ubiquitin-26S proteasome system-mediated protein
      degradation and it is known to regulate most, if not all, important cellular
      processes. Here, we investigated the response to the inhibition of the proteasome
      at the protein level treating leaves with the specific inhibitor Syringolin A
      (SylA) in a daytime specific manner and found 109 accumulated and 140 decreased
      proteins. The patterns of protein level changes indicate that the accumulating
      proteins cause proteotoxic stress that triggers various responses. Comparing
      protein level changes in SylA treated with those in a transgenic line over
      expressing a mutated ubiquitin unable to form polyubiquitylated proteins produced
      little overlap pointing to different response pathways. To distinguish between
      direct and indirect targets of the UPS we also enriched and identified
      ubiquitylated proteins after inhibition of the proteasome, revealing a total of
      1791 ubiquitylated proteins in leaves and roots and 1209 that were uniquely
      identified in our study. The comparison of the ubiquitylated proteins with those
      changing in abundance after SylA-mediated inhibition of the proteasome confirmed
      the complexity of the response and revealed that some proteins are regulated both
      at transcriptional and post-transcriptional level. For the ubiquitylated proteins
      that accumulate in the cytoplasm but are targeted to the plastid or the
      mitochondrion, we often found peptides in their target sequences, demonstrating
      that the UPS is involved in controlling organellar protein levels. Attempts to
      identify the sites of ubiquitylation revealed that the specific properties of
      this post-translational modification can lead to incorrect peptide spectrum
      assignments in complex peptide mixtures in which only a small fraction of
      peptides is expected to carry the ubiquitin footprint. This was confirmed with
      measurements of synthetically produced peptides and calculating the similarities
      between the different spectra. 

PMID- 24732915
TI  - Urologic considerations of placenta accreta: a contemporary tertiary care
      institutional experience.
AB  - BACKGROUND: As the incidence of cesarean delivery has increased, we are
      experiencing a higher incidence of subsequent placenta accreta and the associated
      complications, including urologic complications. METHODS: This is a retrospective
      review of all patients delivered from 2000 to 2011 with a histologically proven
      diagnosis of placenta accreta. Data were analyzed for baseline maternal
      characteristics, intraoperative and postoperative outcomes and complications.
      RESULTS: 83 patients were included in the analysis. The depth of placenta accreta
      invasion varied in the cohort, with 48, 25 and 27% being classified as placenta
      accreta, placenta increta and placenta percreta, respectively. 88% of patients
      had had a previous cesarean delivery, and 58% had more than one prior operative
      delivery. Cystotomy was encountered in 27% of patients and ureteral injury
      occurred in 4%. Degree of placenta accreta invasion, number of prior cesarean
      deliveries and intraoperative blood loss were associated with a higher likelihood
      of urologic injury. CONCLUSIONS: Urologic injuries are among the most frequently
      encountered intraoperative complications of placenta accreta. Surgeons involved
      in these cases need to be aware of this risk and maintain a high level of
      surveillance intraoperatively.

PMID- 24732914
TI  - Modulation of the chromatin phosphoproteome by the Haspin protein kinase.
AB  - Recent discoveries have highlighted the importance of Haspin kinase activity for
      the correct positioning of the kinase Aurora B at the centromere. Haspin
      phosphorylates Thr(3) of the histone H3 (H3), which provides a signal for Aurora
      B to localize to the centromere of mitotic chromosomes. To date, histone H3 is
      the only confirmed Haspin substrate. We used a combination of biochemical,
      pharmacological, and mass spectrometric approaches to study the consequences of
      Haspin inhibition in mitotic cells. We quantified 3964 phosphorylation sites on
      chromatin-associated proteins and identified a Haspin protein-protein interaction
      network. We determined the Haspin consensus motif and the co-crystal structure of
      the kinase with the histone H3 tail. The structure revealed a unique bent
      substrate binding mode positioning the histone H3 residues Arg(2) and Lys(4)
      adjacent to the Haspin phosphorylated threonine into acidic binding pockets. This
      unique conformation of the kinase-substrate complex explains the reported
      modulation of Haspin activity by methylation of Lys(4) of the histone H3. In
      addition, the identification of the structural basis of substrate recognition and
      the amino acid sequence preferences of Haspin aided the identification of novel
      candidate Haspin substrates. In particular, we validated the phosphorylation of
      Ser(137) of the histone variant macroH2A as a target of Haspin kinase activity.
      MacroH2A Ser(137) resides in a basic stretch of about 40 amino acids that is
      required to stabilize extranucleosomal DNA, suggesting that phosphorylation of
      Ser(137) might regulate the interactions of macroH2A and DNA. Overall, our data
      suggest that Haspin activity affects the phosphorylation state of proteins
      involved in gene expression regulation and splicing.

PMID- 24732916
TI  - PTP1B inhibition causes Rac1 activation by enhancing receptor tyrosine kinase
      signaling.
AB  - BACKGROUND/AIMS: The present study investigated the signaling pathway underlying
      Rac1 activation induced by the linoleic acid derivative 8-[2-(2-pentyl
      cyclopropylmethyl)-cyclopropyl]-octanoic acid (DCP-LA). METHODS: Activity of
      protein tyrosine phosphatase 1B (PTP1B) was assayed under cell-free conditions.
      Western blot was carried out to quantify phosphorylation of insulin receptor
      substrate-1 (IRS-1) and Akt in PC-12 cells. Rac1 activity was monitored in the
      foerster resonance energy transfer (FRET) analysis using living and fixed PC-12
      cells. RESULTS: DCP-LA markedly suppressed PTP1B activity in a concentration (100
      pM-100 uM)-dependent manner. In the DCP-LA binding assay, fluorescein-conjugated
      DCP-LA produced a single fluorescent signal band at 60 kDa, corresponding to the
      molecule of PTP1B, and the signal was attenuated or abolished by co-treatment or
      pretreatment with non-conjugated DCP-LA. DCP-LA significantly enhanced nerve
      growth factor (NGF)-stimulated phosphorylation of IRS-1 at Tyr1222 and Akt1/2 at
      Thr308/309 and Ser473/474 in PC-12 cells. In the FRET analysis, DCP-LA
      significantly enhanced NGF-stimulated Rac1 activation, which is abrogated by the
      phosphatidylinositol 3 kinase (PI3K) inhibitor wortmannin, the 3-phosphoinositide
      dependent protein kinase-1 (PDK1) inhibitor BX912, or the Akt inhibitor MK2206.
      CONCLUSION: The results of the present study show that DCP-LA-induced PTP1B
      inhibition, possibly through its direct binding, causes Rac1 activation by
      enhancing a pathway along a receptor tyrosine kinase (RTK)/IRS-1/PI3K/Akt/Rac1
      axis.

PMID- 24732917
TI  - Efficacy of chest compressions directed by end-tidal CO2 feedback in a pediatric
      resuscitation model of basic life support.
AB  - BACKGROUND: End-tidal carbon dioxide (ETCO2) correlates with systemic blood flow
      and resuscitation rate during cardiopulmonary resuscitation (CPR) and may
      potentially direct chest compression performance. We compared ETCO2-directed
      chest compressions with chest compressions optimized to pediatric basic life
      support guidelines in an infant swine model to determine the effect on rate of
      return of spontaneous circulation (ROSC). METHODS AND RESULTS: Forty 2-kg piglets
      underwent general anesthesia, tracheostomy, placement of vascular catheters,
      ventricular fibrillation, and 90 seconds of no-flow before receiving 10 or 12
      minutes of pediatric basic life support. In the optimized group, chest
      compressions were optimized by marker, video, and verbal feedback to obtain
      American Heart Association-recommended depth and rate. In the ETCO2-directed
      group, compression depth, rate, and hand position were modified to obtain a
      maximal ETCO2 without video or verbal feedback. After the interval of pediatric
      basic life support, external defibrillation and intravenous epinephrine were
      administered for another 10 minutes of CPR or until ROSC. Mean ETCO2 at 10
      minutes of CPR was 22.7+/-7.8 mm Hg in the optimized group (n=20) and 28.5+/-7.0
      mm Hg in the ETCO2-directed group (n=20; P=0.02). Despite higher ETCO2 and mean
      arterial pressure in the latter group, ROSC rates were similar: 13 of 20 (65%;
      optimized) and 14 of 20 (70%; ETCO2 directed). The best predictor of ROSC was
      systemic perfusion pressure. Defibrillation attempts, epinephrine doses required,
      and CPR-related injuries were similar between groups. CONCLUSIONS: The use of
      ETCO2-directed chest compressions is a novel guided approach to resuscitation
      that can be as effective as standard CPR optimized with marker, video, and verbal
      feedback.

PMID- 24732918
TI  - Need for prophylactic application of verapamil in transradial coronary
      procedures: a randomized trial. The VITRIOL (is Verapamil In TransRadial
      Interventions OmittabLe?) trial.
AB  - BACKGROUND: Verapamil is traditionally applied prophylactically in transradial
      procedures to prevent radial artery spasm. However, verapamil may have side
      effects and is contraindicated in some clinical settings. METHODS AND RESULTS:
      During an investigator-initiated, randomized, double-blind trial, we evaluated
      the need for preventive verapamil administration. After vascular access was
      established, patients received either 5 mg verapamil (n=297) or placebo (n=294).
      We compared the rate of access site conversions as primary end point using a
      superiority margin of 5%. Occurrence of code breaks (composite of conversions and
      unplanned use of verapamil), overall verapamil use, procedural and fluoroscopic
      times, contrast volume, and subjective pain were investigated as secondary end
      points. The rate of access site conversions was not different in the 2 arms
      (placebo 1.7% versus verapamil 0.7%, P=0.28, difference 1.0%, 95% CI for the
      difference -1.1% to 3.3%). Proportion of code breaks was similar in the 2 groups
      (3.4% versus 1.3%, P=0.11), whereas overall verapamil use was markedly lower in
      the placebo arm (2.0% versus 100%, P<0.0001). Procedural time (median [IQR] 16.0
      minutes [9.0 to 30.0 minutes] versus 17.0 minutes [10.0 to 31.0 minutes],
      P=0.37), fluoroscopic time (4.4 minutes [2.1 to 9.6 minutes] versus 4.8 minutes
      [2.4 to 10.7 minutes], P=0.28), contrast volume (72.5 mL [48.0 to 146.0 mL]
      versus 75.5 mL [47.0 to 156.5 mL], P=0.74), and pain score (P for trend=0.12)
      were comparable in the 2 groups. CONCLUSIONS: The preventive use of verapamil may
      be unnecessary for transradial procedures. The omission of prophylactic verapamil
      may not only reduce the rate of potential complications related to the drug but
      also allow the safe extension of the transradial method to those with
      contraindications to verapamil. CLINICAL TRIAL REGISTRATION URL:
      http://www.clinicaltrials.gov. Unique identifier: NCT01402427.

PMID- 24732919
TI  - Tetanus toxoid-pulsed monocyte vaccination for augmentation of collateral vessel
      growth.
AB  - BACKGROUND: The pathogenesis of collateral growth (arteriogenesis) has been
      linked to both the innate and adaptive immune systems. While therapeutic
      approaches for the augmentation of arteriogenesis have focused on innate
      immunity, exploiting both innate and adaptive immune responses has not been
      examined. We hypothesized that tetanus toxoid (tt) immunization of mice followed
      by transplantation of monocytes (Mo) exposed ex vivo to tt augments
      arteriogenesis after ligation of the hind limb. METHODS AND RESULTS: Mo were
      generated from nonimmunized BALB/c mice, exposed ex vivo to tt for 24 hours and
      intravenously injected (ttMo, 2.5*10(6)) into the tail veins of tt-immunized
      syngeneic mice whose hind limbs had been ligated 24 hours prior to
      transplantation. Laser Doppler perfusion imaging was applied, and a perfusion
      index (PI) was calculated (ratio ligated/unligated). Twenty-one days after
      ligation, the arteriogenesis of untreated BALB/c mice was limited (PI=0.49+/
      0.09). Hind limb function was impaired in 80% of animals. Injection of non
      engineered Mo insignificantly increased the PI to 0.56+/-0.07. However, ttMo
      transplantation resulted in a strong increase of the PI to 0.82+/-0.08 (n=7;
      P<0.001), with no (0%) detectable functional impairment. ttMo injected into
      nonimmunized mice had no effect. The strong arteriogenic response of ttMo
      transplantation into immunized mice was prevented when mice had been depleted of
      T-helper cells by CD4-antibody pretreatment (PI=0.50+/-0.08; n=17; P<0.001),
      supporting the hypothesis that transplanted cells interact with recipient
      lymphocytes. CONCLUSIONS: Transplantation of ttMo into pre-immunized mice
      strongly promotes arteriogenesis. This therapeutic approach is feasible and
      highly attractive for the alleviation of morbidity associated with vascular
      occlusive disease.

PMID- 24732920
TI  - Relations of change in plasma levels of LDL-C, non-HDL-C and apoB with risk
      reduction from statin therapy: a meta-analysis of randomized trials.
AB  - BACKGROUND: Identifying the best markers to judge the adequacy of lipid-lowering
      treatment is increasingly important for coronary heart disease (CHD) prevention
      given that several novel, potent lipid-lowering therapies are in development.
      Reductions in LDL-C, non-HDL-C, or apoB can all be used but which most closely
      relates to benefit, as defined by the reduction in events on statin treatment, is
      not established. METHODS AND RESULTS: We performed a random-effects frequentist
      and Bayesian meta-analysis of 7 placebo-controlled statin trials in which LDL-C,
      non-HDL-C, and apoB values were available at baseline and at 1-year follow-up.
      Summary level data for change in LDL-C, non-HDL-C, and apoB were related to the
      relative risk reduction from statin therapy in each trial. In frequentist meta
      analyses, the mean CHD risk reduction (95% CI) per standard deviation decrease in
      each marker across these 7 trials were 20.1% (15.6%, 24.3%) for LDL-C; 20.0%
      (15.2%, 24.7%) for non-HDL-C; and 24.4% (19.2%, 29.2%) for apoB. Compared within
      each trial, risk reduction per change in apoB averaged 21.6% (12.0%, 31.2%)
      greater than changes in LDL-C (P<0.001) and 24.3% (22.4%, 26.2%) greater than
      changes in non-HDL-C (P<0.001). Similarly, in Bayesian meta-analyses using
      various prior distributions, Bayes factors (BFs) favored reduction in apoB as
      more closely related to risk reduction from statins compared with LDL-C or non
      HDL-C (BFs ranging from 484 to 2380). CONCLUSIONS: Using both a frequentist and
      Bayesian approach, relative risk reduction across 7 major placebo-controlled
      statin trials was more closely related to reductions in apoB than to reductions
      in either non-HDL-C or LDL-C.

PMID- 24732921
TI  - Early clopidogrel versus prasugrel use among contemporary STEMI and NSTEMI
      patients in the US: insights from the National Cardiovascular Data Registry.
AB  - BACKGROUND: P2Y12 antagonist therapy improves outcomes in acute myocardial
      infarction (MI) patients. Novel agents in this class are now available in the US.
      We studied the introduction of prasugrel into contemporary MI practice to
      understand the appropriateness of its use and assess for changes in antiplatelet
      management practices. METHODS AND RESULTS: Using ACTION Registry-GWTG (Get-with
      the-Guidelines), we evaluated patterns of P2Y12 antagonist use within 24 hours of
      admission in 100 228 ST elevation myocardial infarction (STEMI) and 158 492 Non
      ST elevation myocardial infarction (NSTEMI) patients at 548 hospitals between
      October 2009 and September 2012. Rates of early P2Y12 antagonist use were
      approximately 90% among STEMI and 57% among NSTEMI patients. From 2009 to 2012,
      prasugrel use increased significantly from 3% to 18% (5% to 30% in STEMI; 2% to
      10% in NSTEMI; P for trend <0.001 for all). During the same period, we observed a
      decrease in use of early but not discharge P2Y12 antagonist among NSTEMI
      patients. Although contraindicated, 3.0% of patients with prior stroke received
      prasugrel. Prasugrel was used in 1.9% of patients >=75 years and 4.5% of patients
      with weight <60 kg. In both STEMI and NSTEMI, prasugrel was most frequently used
      in patients at the lowest predicted risk for bleeding and mortality. Despite lack
      of supporting evidence, prasugrel was initiated before cardiac catheterization in
      18% of NSTEMI patients. CONCLUSIONS: With prasugrel as an antiplatelet treatment
      option, contemporary practice shows low uptake of prasugrel and delays in P2Y12
      antagonist initiation among NSTEMI patients. We also note concerning evidence of
      inappropriate use of prasugrel, and inadequate targeting of this more potent
      therapy to maximize the benefit/risk ratio.

PMID- 24732922
TI  - Hormonal control of metabolism by the hypothalamus-autonomic nervous system-liver
      axis.
AB  - The hypothalamus has long been appreciated to be fundamental in the control and
      coordination of homeostatic activity. Historically, this has been viewed in terms
      of the extensive neuroendocrine control system resulting from processing of
      hypothalamic signals relayed to the pituitary. Through these actions, endocrine
      signals are integrated throughout the body, modulating a vast array of
      physiological processes. Our understanding of the responses to endocrine signals
      is crucial for the diagnosis and management of many pathological conditions. More
      recently, the control emanating from the hypothalamus over the autonomic nervous
      system has been increasingly recognized as a powerful additional modulator of
      peripheral tissues. However, the neuroendocrine and autonomic control pathways
      emanating from the hypothalamus are not separate processes. They appear to act as
      a single integrated regulatory system, far more subtle and complex than when each
      is viewed in isolation. Consequently, hypothalamic regulation should be viewed as
      a summation of both neuroendocrine and autonomic influences. The neural
      regulation is believed to be fine and rapid, whereas the hormonal regulation is
      more stable and widespread. In this chapter, we will focus on the hypothalamic
      control of hepatic glucose and lipid metabolism.

PMID- 24732923
TI  - The blood-brain barrier as a regulator of the gut-brain axis.
AB  - The gut-brain axis is involved in metabolic homeostasis through optimization of
      nutrient absorption and appetite regulation, and encompasses a two-way
      communication between the gastrointestinal tract and neural circuits in the
      brain. An important feature of this axis is the secretion of gut-derived peptide
      hormones which signal energy status to the brain, provoking adaptive behaviors
      such as food intake or satiation. However, the major integrator of gut signals,
      the arcuate nucleus of the hypothalamus, is protected by blood-brain barrier, an
      obstacle to free diffusion of circulating molecules. The aim of this chapter is
      to therefore review and summarize recent findings regarding the mechanisms
      underlying entry of gastrointestinal tract hormones into the central nervous
      system, and identify how these become dysregulated in socioeconomically-costly
      metabolic diseases such as obesity and type 2 diabetes.

PMID- 24732924
TI  - The brain modulates insulin sensitivity in multiple tissues.
AB  - Insulin sensitivity is determined by direct effects of circulating insulin on
      metabolically active tissues in combination with indirect effects of circulating
      insulin, i.e. via the central nervous system. The dose-response effects of
      insulin differ between the various physiological effects of insulin. At lower
      insulin concentrations, circulating insulin inhibits endogenous glucose
      production through a combination of direct and indirect effects. At higher
      insulin concentrations, circulating insulin also stimulates glucose uptake and
      fatty acid uptake in adipose tissue, again through direct and indirect effects.
      High-fat diet induces insulin resistance in the central nervous system, which
      contributes considerably to overall insulin resistance of liver and peripheral
      tissues. Central insulin resistance is amendable to therapeutic intervention,
      reflected in the central effects of topiramate and glucagon-like peptide-1 on
      hepatic and peripheral insulin resistance in insulin resistant mice.

PMID- 24732925
TI  - The important role of sleep in metabolism.
AB  - Both reduction in total sleep duration with slow-wave sleep (SWS) largely
      preserved and alterations of sleep quality (especially marked reduction of SWS)
      with preservation of total sleep duration are associated with insulin resistance
      without compensatory increase in insulin secretion, resulting in impaired glucose
      tolerance and increased risk of type 2 diabetes. When performed under rigorously
      controlled conditions of energy intake and physical activity, sleep restriction
      is also associated with a decrease in circulating levels of leptin (an
      anorexigenic hormone) and an increase in circulating levels of ghrelin (an
      orexigenic hormone), hunger and appetite. Furthermore, sleep restriction is also
      associated with a stimulation of brain regions sensitive to food stimuli,
      indicating that sleep loss may lead to obesity through the selection of high
      calorie food. There is also evidence that sleep restriction could provide a
      permissive environment for the activation of genes that promote obesity. Indeed,
      the heritability of body mass index is increased in short sleepers. Thus, chronic
      sleep curtailment, which is on the rise in modern society, including in children,
      is likely to contribute to the current epidemics of type 2 diabetes and obesity.

PMID- 24732926
TI  - Metabolic interplay between gut bacteria and their host.
AB  - Shifts in the bacterial composition of the human gut microbiota (i.e. dysbiosis)
      have been associated with digestive tract dysfunctions such as inflammatory bowel
      diseases. More strikingly, strong evidence, from both human studies and germ-free
      animal models, links intestinal microbiota dysbiosis with metabolic disorders,
      such as obesity and liver diseases. This chapter focuses on the changes and
      impact of the gut microbiota during these diseased states, and describes the
      possible direct and indirect mechanisms that an aberrant gut microbiota can
      promote metabolic dysregulations. The possible involvement of the 'microbiota-gut
      brain' axis in the development of obesity is further discussed, as is the
      perspective of meta-omic technologies that give insight into the functions and
      potential effect of the non-cultured intestinal bacteria on the host health.
      Understanding how modifications in this finely tuned ecosystem lead to these
      pathological processes is crucial for the development of new therapeutic
      approaches to treat and hopefully ameliorate these metabolic diseases.

PMID- 24732927
TI  - The brain-stomach connection.
AB  - The stomach-brain connection has been revealed to be one of the most promising
      targets in treating obesity. The stomach plays a key role in the homeostatic
      mechanism implicating stomach-brain communication regulated under neural and
      hormonal control. The present review explores specific topics related to gut
      brain interactions focus on the stomach-brain connection through the different
      known systems implied in energy balance control as ghrelin, and nesfatin.
      Moreover, novel mechanisms for energy balance regulation involving gastric-brain
      communication are described including the role of the gastric intracellular
      mTOR/S6K1 pathway mediating the interaction among ghrelin, nesfatin and
      endocannabinoid gastric systems to modulate metabolism.

PMID- 24732928
TI  - Prader-Willi syndrome as a model of human hyperphagia.
AB  - Prader-Willi syndrome (PWS), first described in 1956, is considered as a paradigm
      of a neurodevelopmental disorder with severe and early obesity with hyperphagia
      and impaired satiety. The improved knowledge in the natural history and recent
      data on genetics offer new perspectives for understanding the metabolic and
      endocrine dysfunctions and possibly for treatment. Natural history of the disease
      has been described due to the early diagnosis performed in the first months of
      life and various nutritional phases have been described. In addition, there is
      clear evidence that the abnormal feeding behavior is included in the behavioral
      problems. Brain imaging studies have shown that some brain regions may be
      important in PWS. The role of SNORD116 gene cluster is detailed and its links
      with circadian rhythm and brain and hypothalamus development. Pathophysiology of
      the abnormal ghrelin levels and of OT dysfunction is documented. While no effect
      on appetite and weight regulation has been reported with ghrelin antagonists, OT
      has been shown to improve some of the behavioral problems in adults. We discuss
      our hypothesis of an abnormal ghrelin/OT/dopamine pathway which may explain the
      switch of nutritional phases and behavior. These new aspects offer an opportunity
      for therapeutic use and possible early intervention.

PMID- 24732929
TI  - Interactions between the gut, the brain and brown adipose tissue function.
AB  - Brown adipose tissue (BAT) has the unique ability to oxidize fatty acids to
      generate heat, a process termed thermogenesis. The mitochondrial uncoupling
      protein 1 is predominantly expressed in BAT and controls the thermogenetic
      properties of this tissue. Since activated BAT dissipates energy, it is
      considered beneficial in controlling metabolism, i.e. by combating obesity.
      Indeed, humans with a higher BMI have less active BAT. Many researchers attempt
      to uncover regulatory pathways in BAT activity in the pursuit for novel BAT
      modulators to control body weight. Endocrine factors such as thyroid hormone, sex
      steroid hormones and glucocorticoids can modulate BAT activity. Since the
      intestinal tract has emerged as an endocrine organ regulating energy balance and
      glucose homeostasis, this review will discuss how gut-derived hormones and other
      intestinal tract-related factors such as bile acids modulate BAT activity.
      Emphasis will be put on whether these hormones regulate BAT directly or via the
      central nervous system. In summary, it can be globally stated that anorexigenic
      gut hormones stimulate BAT while orexigenic gut hormones inhibit BAT activity.
      How these hormones modulate BAT and whether this is via a direct and/or central
      effect is largely unknown. Novel insights about gut-derived factors such as bile
      acids suggest that they also affect BAT activity. Altogether, effects of food
      intake per se on BAT activity are rather complex to interpret and depend on many
      (hormonal) factors.

PMID- 24732930
TI  - Gut sweet taste receptors and their role in metabolism.
AB  - Obesity is caused by an imbalance between food intake and energy expenditure. In
      recent decades the gastrointestinal tract has received growing attention as a
      control parameter for the regulation of appetite and food intake, however
      regulatory circuits and their interactions are complex. The basic understanding
      on the role of the gut starts with the notion 'we are what we eat'. Food enters
      the gastrointestinal tract, which then triggers specific mechanisms or a sensing
      machinery that respond to specific components of food. Enteroendocrine cells in
      the small intestine are the anatomical basis for the sensing machinery, which act
      as neural triggers or as intestinal satiation peptide-secreting cells. These
      cells express chemosensory receptors that respond to luminal stimuli. The
      understanding of each gastrointestinal mechanism that might be involved in the
      process of eating provides a basis for the assessment of the potential of the
      gastrointestinal tract in the fight against obesity. This review discusses the
      function of the gut sweet taste receptor T1R2/T1R3 in sensing sweet compounds, as
      well as its role in gastrointestinal peptide secretion and glucose metabolism.

PMID- 24732931
TI  - What is the role of metabolic hormones in taste buds of the tongue.
AB  - Gustation is one of the important chemical senses that guides the organism to
      identify nutrition while avoiding toxic chemicals. An increasing number of
      metabolic hormones and/or hormone receptors have been identified in the taste
      buds of the tongue and are involved in modulating taste perception. The gustatory
      system constitutes an additional endocrine regulatory locus that affects food
      intake, and in turn whole-body energy homeostasis. Here we provide an overview of
      the main metabolic hormones known to be present in the taste buds of the tongue;
      discuss their potential functional roles in taste perception and energy
      homeostasis and how their functional integrity is altered in the metabolic
      imbalance status (obesity and diabetes) and aging process. Better understanding
      of the functional roles of metabolic hormones in flavor perception as well as the
      link between taste perception and peripheral metabolism may be vital for
      developing strategies to promote healthier eating and prevent obesity or
      lifestyle-related disorders.

PMID- 24732932
TI  - Protein PYY and its role in metabolism.
AB  - The hormone PYY is released from the distal gut in response to nutrient
      ingestion. Numerous studies have shown that PYY3-36, the most abundant
      circulating isoform of PYY, reduces food intake when given to obese rodents and
      humans. Its infusion to mimic postprandial levels in fasting subjects inhibits
      appetite, suggesting a physiological role in postprandial satiety. However, the
      mechanisms underlying this effect remain unclear. Neuronal activity within
      several brain areas appears to be modified following peripheral administration of
      PYY3-36 and a direct effect on the central nervous system is possible. Several
      studies suggest that PYY3-36 levels are reduced in obesity and are elevated
      following gastric bypass surgery, possibly contributing to the increased feelings
      of satiety following this procedure. Whether PYY has a role in the regulation of
      energy expenditure is currently unclear. However, due to the clear appetite
      inhibitory effect of PYY, this hormone continues to be investigated as a
      potential therapeutic agent in the treatment of obesity.

PMID- 24732933
TI  - Nutropioids regulate gut-brain circuitry controlling food intake.
AB  - The modulation of hunger sensations by the u-opioid receptor (MOR) present in the
      brain is an established fact. That MORs expressed in the periphery could have a
      similar role was outstanding. Using portal infusions of agonists and/or
      antagonists of MOR in conscious rodents, we have shown that MORs present in the
      walls of the portal vein nervous system control a gut-brain circuit of induction
      of intestinal gluconeogenesis (IGN), a function controlling hunger sensations.
      Then, we have shown that peptides and proteins promote a MOR-dependent induction
      of IGN. Peptides have no effect in mice knockout for MOR. MOR-KO mice are also
      insensitive to satiety induced by protein-enriched diets. In addition, portal
      infusions of MOR modulators have no effect on food intake in mice deficient for
      IGN. Thus, the regulation by portal MORs and peptides of a gut-brain neural
      circuit of induction of IGN is a causal link in the phenomenon of satiety induced
      by dietary protein.

PMID- 24732934
TI  - Should we consider des-acyl ghrelin as a separate hormone and if so, what does it
      do?
AB  - The peptides ghrelin (or acyl ghrelin; AG), des-acyl ghrelin (DAG) and obestatin
      are all encoded by the prepro-ghrelin gene that is expressed predominantly in the
      stomach. Compared with ghrelin and obestatin, DAG has not received a great amount
      of attention. DAG has long been considered an inert degradation product of AG.
      Recent evidence, however, indicates that DAG behaves like a separate hormone.
      Therefore, it is believed that DAG must activate its own receptor, and that it
      may also interact with AG at this receptor. DAG can act together with AG, can
      antagonize AG and seems to have AG-independent effects. Of potential clinical
      importance is that an increasing number of studies suggest that DAG is a
      functional inhibitor of AG. Therefore, DAG or DAG analogs are being trialed in
      early clinical studies for treatment of metabolic disorders such as diabetes,
      obesity and Prader-Willi syndrome.

PMID- 24732935
TI  - Obestatin: is it really doing something?
AB  - Obestatin was identified in 2005 by Zhang and colleagues as a ghrelin-associated
      peptide, derived from posttranslational processing of the prepro-ghrelin gene.
      Initially, obestatin was reported to activate the G-protein-coupled receptor
      GPR39 and to reduce food intake and gastric emptying. However, obestatin remains
      a controversial peptide, as these findings have been questioned and its receptor
      is still a matter of debate, as well as its effects on feeding behavior.
      Recently, interaction with the glucagon-like peptide 1 receptor has been
      suggested, in line with obestatin-positive effects on glucose and lipid
      metabolism. In addition, obestatin displays a variety of cellular effects, by
      regulating metabolic cell functions, increasing cell survival and proliferation,
      and inhibiting apoptosis and inflammation in different cell types. Finally, like
      ghrelin, obestatin is produced in the gastrointestinal tract, including the
      pancreas and adipose tissue, and exerts both local actions in peripheral tissues,
      and distant effects at the central level. Therefore, obestatin may indeed be
      considered a hormone, although additional studies are required to clarify its
      physiopathological role and to definitely identify its receptor.

PMID- 24732936
TI  - Translating between social worlds of policy and everyday life: The development of
      a group-based method to support policymaking by exploring behavioural aspects of
      sustainable consumption.
AB  - A large international literature on how lay citizens make sense of various
      aspects of science and technology has been generated by investigations which
      utilise small group methods. Within that literature, focus group and other group
      based methods have come to co-exist, and to some extent, hybridise, with the use
      of small groups in citizen engagement initiatives. In this article, we report on
      how we drew upon these methodological developments in the design and
      operationalisation of a policymaking support tool (STAVE). This tool has been
      developed to gain insight, in a relatively speedy and cost-effective way, into
      practical details of the everyday lived experience of people's lives, as relating
      to the sustainability of corresponding practices. An important challenge we faced
      was how, in Kuhn's terms, to 'translate' between the forms of life corresponding
      to the world of policymaking and the world of everyday domestic life. We examine
      conceptual and methodological aspects of how the tool was designed and assembled,
      and then trialled in the context of active real-world collaborations with
      policymaking organisations. These trials were implemented in six European
      countries, where they were used to support work on live policy issues concerned
      with sustainable consumption. 

PMID- 24732937
TI  - Pregnancy in obese mice protects selectively against visceral adiposity and is
      associated with increased adipocyte estrogen signalling.
AB  - Maternal obesity is linked with increased adverse pregnancy outcomes for both
      mother and child. The metabolic impact of excessive fat within the context of
      pregnancy is not fully understood. We used a mouse model of high fat (HF) feeding
      to induce maternal obesity to identify adipose tissue-mediated mechanisms driving
      metabolic dysfunction in pregnant and non-pregnant obese mice. As expected,
      chronic HF-feeding for 12 weeks preceding pregnancy increased peripheral
      (subcutaneous) and visceral (mesenteric) fat mass. However, unexpectedly at late
      gestation (E18.5) HF-fed mice exhibited a remarkable normalization of visceral
      but not peripheral adiposity, with a 53% reduction in non-pregnant visceral fat
      mass expressed as a proportion of body weight (P<0.001). In contrast, in control
      animals, pregnancy had no effect on visceral fat mass proportion. Obesity
      exaggerated glucose intolerance at mid-pregnancy (E14.5). However by E18.5, there
      were no differences, in glucose tolerance between obese and control mice.
      Transcriptomic analysis of visceral fat from HF-fed dams at E18.5 revealed
      reduced expression of genes involved in de novo lipogenesis (diacylglycerol O
      acyltransferase 2--Dgat2) and inflammation (chemokine C-C motif ligand 20--Ccl2)
      and upregulation of estrogen receptor alpha (ERalpha) compared to HF non
      pregnant. Attenuation of adipose inflammation was functionally confirmed by a 45%
      reduction of CD11b+CD11c+ adipose tissue macrophages (expressed as a proportion
      of all stromal vascular fraction cells) in HF pregnant compared to HF non
      pregnant animals (P<0.001). An ERalpha selective agonist suppressed both de novo
      lipogenesis and expression of lipogenic genes in adipocytes in vitro. These data
      show that, in a HF model of maternal obesity, late gestation is associated with
      amelioration of visceral fat hypertrophy, inflammation and glucose intolerance,
      and suggest that these effects are mediated in part by elevated visceral
      adipocyte ERalpha signaling.

PMID- 24732938
TI  - Evaluation of inferior alveolar nerve regeneration by bifocal distraction
      osteogenesis with retrograde transportation of horseradish peroxidase in dogs.
AB  - BACKGROUND: Bifocal distraction osteogenesis has been shown to be a reliable
      method for reconstructing segmental mandibular defects. However, there are few
      reports regarding the occurrence of inferior alveolar nerve regeneration during
      the process of distraction. Previously, we reported inferior alveolar nerve
      regeneration after distraction, and evaluated the regenerated nerve using
      histological and electrophysiological methods. In the present study, we
      investigated axons regenerated by bifocal distraction osteogenesis using
      retrograde transportation of horseradish peroxidase in the mandibles of dogs to
      determine their type and function. METHODS AND FINDINGS: Using a bifocal
      distraction osteogenesis method, we produced a 10-mm mandibular defect, including
      a nerve defect, in 11 dogs and distracted using a transport disk at a rate of 1
      mm/day. The regenerated inferior alveolar nerve was evaluated by retrograde
      transportation of HRP in all dogs at 3 and 6 months after the first operation. At
      3 and 6 months, HRP-labeled neurons were observed in the trigeminal ganglion. The
      number of HRP-labeled neurons in each section increased, while the cell body
      diameter of HRP-labeled neurons was reduced over time. CONCLUSIONS: We found that
      the inferior alveolar nerve after bifocal distraction osteogenesis successfully
      recovered until peripheral tissue began to function. Although our research is
      still at the stage of animal experiments, it is considered that it will be
      possible to apply this method in the future to humans who have the mandibular
      defects.

PMID- 24732939
TI  - Transumbilical multiport laparoscopic nephrectomy with specimen extraction
      through the vagina.
AB  - OBJECTIVES: To report our initial experience with transumbilical multiport
      laparoscopic nephrectomy (TMLN) with transvaginal specimen extraction. PATIENTS
      AND METHODS: Between January and July 2010, 5 married and parous female patients
      were submitted to TMLN with transvaginal specimen extraction in our center. All
      data referring to patient demographics, surgery, pathology and perioperative
      outcomes were recorded. Sexual function was assessed with the Female Sexual
      Function Index questionnaire before and after surgery. The cosmetic result was
      investigated by administering the Patient Scar Assessment Questionnaire and
      Scoring System (PSAQ). RESULTS: All procedures were completed successfully. The
      mean operative time was 136 min (range 110-160 min, standard deviation [SD]
      20.7). The mean estimated blood loss was 66 ml (range 40-100 ml, SD 24.1). The
      mean postoperative hospitalization stay was 4.8 days (range 4-6 days, SD 0.8).
      All patients reported unaltered sexual function after surgery. The better
      cosmetic results were confirmed by the PSAQ score. CONCLUSIONS: TMLN with
      transvaginal specimen extraction is feasible and safe for married and parous
      female patients. This technique is a natural evolution towards natural orifice
      transluminal endoscopic surgery (NOTES). By acting as an intermediate-type
      procedure, it provides a bridge through which NOTES may ultimately gain clinical
      acceptance.

PMID- 24732940
TI  - Evaluation of the comparative efficacy and safety of artemether-lumefantrine,
      artesunate-amodiaquine and artesunate-amodiaquine-chlorpheniramine (ArtemocloTM)
      for the treatment of acute uncomplicated malaria in Nigerian children.
AB  - OBJECTIVE: To evaluate the comparative efficacy and safety of artemether
      lumefantrine (AL), artesunate-amodiaquine (ASAQ) and artesunate-amodiaquine
      chlorpheniramine (AQC) for the treatment of acute uncomplicated malaria among
      Southwest Nigerian children. SUBJECTS AND METHODS: One hundred and sixty children
      aged 6 months to 14 years with acute uncomplicated malaria were randomized to AL
      (n = 53), ASAQ (n = 53), or AQC (n = 54). Enrollees were seen daily on days 0-3
      and then on days 7, 14, 21, 28 and 42 for clinical and parasitological
      evaluations. Paired samples of genomic DNA at enrolment and at the time of
      recurrent parasitaemia were genotyped using nested PCR to distinguish between
      reinfection and recrudescence. Detailed haematological and biochemical
      evaluations were carried out in a subset of enrollees on days 0, 7 and 28 as part
      of a safety evaluation. RESULTS: Of the 160 children, 144 (90%) completed the
      study. The mean fever clearance times and parasite clearance times for AL, ASAQ
      and AQC were comparable (p = 0.94 and p = 0.122, respectively). On day 14, the
      adequate clinical and parasitological response (ACPR) for AL and AQC was 100% and
      for ASAQ it was 90% (p = 0.39). The PCR-uncorrected results on days 28 and 42 and
      the ACPR-corrected results on day 42 were similar for all drugs (p = 0.62 and p =
      0.56, respectively). AQC resulted in the best parasite clearance and
      haematological recovery on day 2 (p = 0.022 and p = 0.018, respectively).
      Biochemical parameters were not adversely affected by the three artemisinin-based
      combination therapies (ACTs) and these were well tolerated. CONCLUSION: The three
      ACTs were efficacious and safe, but AQC resulted in a better haematological
      recovery on day 2 and higher cure rates throughout the study period.

PMID- 24732941
TI  - Melanoma: Why is sentinel lymph node biopsy 'standard of care' for melanoma?

PMID- 24732942
TI  - Basic research: Rebooting rhabdomyosarcoma's operating system.

PMID- 24732943
TI  - Screening: Where does stool DNA testing FIT in the CRC screening menu?

PMID- 24732944
TI  - Melanoma: MSLT-1--putting sentinel lymph node biopsy into context.

PMID- 24732945
TI  - Genetics: SMARCA4 mutated in SCCOHT.

PMID- 24732947
TI  - High resolution imaging beyond the acoustic diffraction limit in deep tissue via
      ultrasound-switchable NIR fluorescence.
AB  - Fluorescence imaging in deep tissue with high spatial resolution is highly
      desirable because it can provide details about tissue's structural, functional,
      and molecular information. Unfortunately, current fluorescence imaging techniques
      are limited either in penetration depth (microscopy) or spatial resolution
      (diffuse light based imaging) as a result of strong light scattering in deep
      tissue. To overcome this limitation, we developed an ultrasound-switchable
      fluorescence (USF) imaging technique whereby ultrasound was used to switch on/off
      the emission of near infrared (NIR) fluorophores. We synthesized and
      characterized unique NIR USF contrast agents. The excellent switching properties
      of these agents, combined with the sensitive USF imaging system developed in this
      study, enabled us to image fluorescent targets in deep tissue with spatial
      resolution beyond the acoustic diffraction limit. 

PMID- 24732946
TI  - Standing the test of time: targeting thymidylate biosynthesis in cancer therapy.
AB  - Over the past 60 years, chemotherapeutic agents that target thymidylate
      biosynthesis and the enzyme thymidylate synthase (TS) have remained among the
      most-successful drugs used in the treatment of cancer. Fluoropyrimidines, such as
      5-fluorouracil and capecitabine, and antifolates, such as methotrexate and
      pemetrexed, induce a state of thymidylate deficiency and imbalances in the
      nucleotide pool that impair DNA replication and repair. TS-targeted agents are
      used to treat numerous solid and haematological malignancies, either alone or as
      foundational therapeutics in combination treatment regimens. We overview the
      pivotal discoveries that led to the rational development of thymidylate
      biosynthesis as a chemotherapeutic target, and highlight the crucial contribution
      of these advances to driving and accelerating drug development in the earliest
      era of cancer chemotherapy. The function of TS as well as the mechanisms and
      consequences of inhibition of this enzyme by structurally diverse classes of
      drugs with distinct mechanisms of action are also discussed. In addition,
      breakthroughs relating to TS-targeted therapies that transformed the clinical
      landscape in some of the most-difficult-to-treat cancers, such as pancreatic,
      colorectal and non-small-cell lung cancer, are highlighted. Finally, new
      therapeutic agents and novel mechanism-based strategies that promise to further
      exploit the vulnerabilities and target resistance mechanisms within the
      thymidylate biosynthesis pathway are reviewed. 

PMID- 24732949
TI  - CXCL10 controls inflammatory pain via opioid peptide-containing macrophages in
      electroacupuncture.
AB  - Acupuncture is widely used for pain treatment in patients with osteoarthritis or
      low back pain, but molecular mechanisms remain largely enigmatic. In the early
      phase of inflammation neutrophilic chemokines direct opioid-containing
      neutrophils in the inflamed tissue and stimulate opioid peptide release and
      antinociception. In this study the molecular pathway and neuroimmune connections
      in complete Freund's adjuvant (CFA)-induced hind paw inflammation and
      electroacupuncture for peripheral pain control were analyzed. Free moving Wistar
      rats with hind paw inflammation were treated twice with electroacupuncture at
      GB30 (Huan Tiao--gall bladder meridian) (day 0 and 1) and analyzed for mechanical
      and thermal nociceptive thresholds. The cytokine profiles as well as the
      expression of opioid peptides were quantified in the inflamed paw.
      Electroacupuncture elicited long-term antinociception blocked by local injection
      of anti-opioid peptide antibodies (beta-endorphin, met-enkephalin, dynorphin A).
      The treatment altered the cytokine profile towards an anti-inflammatory pattern
      but augmented interferon (IFN)-gamma and the chemokine CXCL10 (IP-10: interferon
      gamma-inducible protein) protein and mRNA expression with concomitant increased
      numbers of opioid peptide-containing CXCR3+ macrophages. In rats with CFA hind
      paw inflammation without acupuncture repeated injection of CXCL10 triggered
      opioid-mediated antinociception and increase opioid-containing macrophages.
      Conversely, neutralization of CXCL10 time-dependently decreased
      electroacupuncture-induced antinociception and the number of infiltrating opioid
      peptide-expressing CXCR3+ macrophages. In summary, we describe a novel function
      of the chemokine CXCL10--as a regulator for an increase of opioid-containing
      macrophages and antinociceptive mediator in inflammatory pain and as a key
      chemokine regulated by electroacupuncture.

PMID- 24732950
TI  - Sedentary behaviors, leisure-time physical inactivity, and chronic diseases in
      Brazilian workers: a cross sectional study.
AB  - BACKGROUND: Our purpose was to examine the association of television viewing
      (hours/day), sedentary work (predominantly sitting at work), passive
      transportation to work (car or motorcycle), and the clustering of these behaviors
      ("sedentary lifestyle"), as well as leisure-time physical inactivity (LTPI), with
      chronic diseases (hypertension, hypercholesterolemia, type 2 diabetes, obesity,
      and clustering of chronic diseases) in Brazilian workers. METHODS: Cross
      sectional study conducted from 2006 to 2008 in 24 Brazilian federal units (n =
      47,477). A questionnaire was applied. Descriptive statistics, binary and
      multinomial logistic regressions were used. RESULTS: Magnitude of association
      with chronic diseases varied greatly across domains and gender. Sedentariness at
      work was the most consistent behavior associated with chronic diseases,
      especially in men (OR hypertension = 1.10, 95% CI: 1.01-1.20; OR
      hypercholesterolemia = 1.34, 95% CI: 1.21-1.48; OR obesity = 1.27, 95% CI: 1.15
      1.41; OR1 chronic disease = 1.17, 95% CI: 1.09-1.26; OR >= 2 chronic diseases =
      1.61, 95% CI: 1.46-1.78) compared with women (OR hypercholesterolemia = 1.15, 95%
      CI: 1.01-1.31; OR obesity = 1.24, 95% CI: 1.04-1.48). LTPI was associated with
      all diseases in men (except type 2 diabetes), but only with obesity in women.
      CONCLUSION: Adverse health consequences may be differently associated according
      to behavior domain and gender. Sedentary work and LTPI were consistently
      associated with chronic disease in Brazilian workers, especially in men.

PMID- 24732948
TI  - Heterogeneous intracellular trafficking dynamics of brain-derived neurotrophic
      factor complexes in the neuronal soma revealed by single quantum dot tracking.
AB  - Accumulating evidence underscores the importance of ligand-receptor dynamics in
      shaping cellular signaling. In the nervous system, growth factor-activated Trk
      receptor trafficking serves to convey biochemical signaling that underlies
      fundamental neural functions. Focus has been placed on axonal trafficking but
      little is known about growth factor-activated Trk dynamics in the neuronal soma,
      particularly at the molecular scale, due in large part to technical hurdles in
      observing individual growth factor-Trk complexes for long periods of time inside
      live cells. Quantum dots (QDs) are intensely fluorescent nanoparticles that have
      been used to study the dynamics of ligand-receptor complexes at the plasma
      membrane but the value of QDs for investigating ligand-receptor intracellular
      dynamics has not been well exploited. The current study establishes that QD
      conjugated brain-derived neurotrophic factor (QD-BDNF) binds to TrkB receptors
      with high specificity, activates TrkB downstream signaling, and allows single QD
      tracking capability for long recording durations deep within the soma of live
      neurons. QD-BDNF complexes undergo internalization, recycling, and intracellular
      trafficking in the neuronal soma. These trafficking events exhibit little time
      synchrony and diverse heterogeneity in underlying dynamics that include phases of
      sustained rapid motor transport without pause as well as immobility of
      surprisingly long-lasting duration (several minutes). Moreover, the trajectories
      formed by dynamic individual BDNF complexes show no apparent end destination;
      BDNF complexes can be found meandering over long distances of several microns
      throughout the expanse of the neuronal soma in a circuitous fashion. The complex,
      heterogeneous nature of neuronal soma trafficking dynamics contrasts the reported
      linear nature of axonal transport data and calls for models that surpass our
      generally limited notions of nuclear-directed transport in the soma. QD-ligand
      probes are poised to provide understanding of how the molecular mechanisms
      underlying intracellular ligand-receptor trafficking shape cell signaling under
      conditions of both healthy and dysfunctional neurological disease models. 

PMID- 24732951
TI  - Lipoprotein-associated phospholipase A2 single-nucleotide polymorphisms and
      cardiovascular events in patients with coronary artery disease.
AB  - AIMS: We tested the hypothesis that variations in the PLA2G7 gene encoding the
      lipoprotein-associated phospholipase A2 (Lp-PLA2), an enzyme deemed to have
      proatherogenic activity, affect the Lp-PLA2 levels and predicts cardiovascular
      events. METHODS: Using a prospective cohort study design, we investigated
      incident cardiovascular events as a function of the PLA2G7 gene for rs1805017,
      rs1805018, and rs1051931 single-nucleotide polymorphisms (SNPs) in 643 randomly
      selected white patients from the GENICA Study, who at baseline underwent coronary
      angiography, measurement of Lp-PLA2 mass and activity. Cardiovascular event-free
      survival was compared across the genotypes by Cox regression, propensity score
      matching, and haplotype analysis. RESULTS: The rs1805018 SNP did not follow the
      Hardy-Weinberg equilibrium and was not further explored. The rs1805017 GG
      genotype had a lower Lp-PLA2 mass and a higher Lp-PLA2 activity, thus suggesting
      that this SNP is functional. Long-term follow-up (median 7.8 years) was obtained
      in 75% of the cohort and allowed recording of incident cardiovascular events in
      25.8% of the patients. On Cox regression analysis, the common rs1805017 GG
      genotype predicted acute myocardial infarction (AMI) [hazard ratio 1.75, 95%
      confidence interval (CI) 1.03-2.99, P = 0.041]; this finding was confirmed on
      propensity score matching (82.6% AMI-free survival in GG vs. 94.4% in GA + AA, P
      = 0.003). The rs1805017 and rs1051931 G/G haplotype was also associated with AMI
      (52.7 vs. 42.2%, P = 0.026) and cardiovascular event incidence (49.5 vs. 41.7%, P
      = 0.025). CONCLUSION: In high-risk coronary artery disease patients of European
      ancestry, the PLA2G7 rs1805017 GG genotype is associated with increased Lp-PLA2
      plasma activity and AMI.

PMID- 24732952
TI  - Use of T-wave alternans in identifying patients with coronary artery disease.
AB  - AIMS: Microvolt T-wave alternans (MTWA) has been found to predict fatal events in
      patients with coronary artery disease (CAD). In a previous study, we found that
      MTWA values are higher in patients with CAD, compared with apparently healthy
      individuals. In this study, we assessed the relation between CAD and MTWA in
      patients with a diagnosis based on coronary angiography results. METHODS: We
      studied 98 consecutive patients undergoing coronary angiography for suspected
      CAD. All patients underwent a maximal exercise stress test (EST), and MTWA was
      measured in the precordial ECG leads. Patients were divided into three groups: 40
      patients without any significant (>50%) stenosis (group 1); 47 patients with
      significant stenosis (group 2); and 11 patients with a previous percutaneous
      coronary intervention (PCI) who had no evidence of restenosis (group 3). EST was
      repeated after 1 month in 24 group 2 patients who underwent PCI and in 17 group 1
      patients. RESULTS: MTWA was significantly higher in group 2 (58.7 +/- 24 MUV)
      compared with group 1 (34.2  +/- 15 MUV, P < 0.01) and group 3 (43.2 +/- 24 MUV,
      P < 0.05). An MTWA greater than 60 MUV had 95% specificity and 82% positive
      predictive value for obstructive CAD. At 1-month follow-up, MTWA decreased
      significantly in patients treated with PCI (from 61.3 +/- 22 to 43.5 +/- 17 MUV;
      P < 0.001), but not in group 1 patients (from 50.5 +/- 22 to 44.3 +/- 19 MUV, P =
      0.19). CONCLUSION: MTWA is increased in patients with obstructive CAD and is
      reduced by coronary revascularization. An assessment of MTWA can be helpful in
      identifying which patients with suspected CAD are likely to show obstructive CAD
      on angiography.

PMID- 24732953
TI  - Structural brain abnormalities in patients with Parkinson's disease with visual
      hallucinations: a comparative voxel-based analysis.
AB  - The objective is to evaluate clinical characteristics and cerebral alterations in
      Parkinson's disease (PD) patients with diurnal visual hallucinations (VHs).
      Assessment was performed using magnetic resonance image (MRI) and voxel-based
      morphometry (VBM). Thirty-nine patients with PD (53.8%) and ten controls were
      studied. Voxel based morphology analysis was performed. Eleven patients presented
      diurnal VHs and among these, six had cognitive dysfunction. Patients with VHs
      performed worse in the mentation-related UPDRS I (p=0.005) and motor-related
      UPDRS III (p=0.02). Patients with VHs showed significant clusters of reduced grey
      matter volume compared to controls in the left opercula frontal gyrus and left
      superior frontal gyrus. PD without hallucinations demonstrated reduced grey
      matter volume in the left superior frontal gyrus compared to controls.
      Comparisons between patients with VHs regarding the presence of cognitive
      dysfunction showed that cases with cognitive dysfunction as compared to those
      without cognitive dysfunction showed significant clusters of reduced grey matter
      volume in the left opercular frontal gyrus. Cases without cognitive dysfunction
      had reduced grey matter substance in the left insula and left trigonal frontal
      gyrus. Judging from our findings, an abnormal frontal cortex, particularly left
      sided insula, frontal opercular, trigonal frontal gyrus and orbital frontal would
      make PD patients vulnerable to hallucinations. Compromise of the left operculum
      distinguished cases with VHs and cognitive dysfunction. Our findings reinforce
      the theoretical concept of a top-down visual processing in the genesis of VHs in
      PD. 

PMID- 24732954
TI  - Self processing in the brain: a paradigmatic fMRI case study with a professional
      singer.
AB  - Understanding the mechanisms involved in perception and conception of oneself is
      a fundamental psychological topic with high relevance for psychiatric and
      neurological issues, and it is one of the great challenges in neuroscientific
      research. The paradigmatic single-case study presented here aimed to investigate
      different components of self- and other-processes and to elucidate corresponding
      neurobiological underpinnings. An eminent professional opera singer with profound
      performance experience has undergone functional magnetic resonance imaging and
      was exposed to excerpts of Mozart arias, sung by herself or another singer. The
      results indicate a distinction between self- and other conditions in cortical
      midline structures, differentially involved in self-related and self-referential
      processing. This lends further support to the assumption of cortical midline
      structures being involved in the neural processing of self-specific stimuli and
      also confirms the power of single case studies as a research tool. 

PMID- 24732955
TI  - Temporospatial analysis of explicit and implicit processing of negative content
      during word comprehension.
AB  - Although divergences between explicit and implicit processing of affective
      content during word comprehension have been reported, the underlying nature of
      those differences remains in dispute. Prior studies focused on either the timing
      or the spatial location of the effects. The present study examined the precise
      dynamics of the processing of negative words when attention is directed to
      affective content or to non-emotional properties by capitalizing on fine temporal
      resolution of the event-related potentials (ERPs) and recent advances in source
      localization. Tasks were used that required accessing knowledge about different
      semantic properties of negative and neutral words. In the direct task,
      participants' attention was directed towards emotional information. By contrast,
      subjects had to decide whether the words' referent could be touched or not in the
      indirect task. Regardless of being processed explicitly or implicitly, negative
      compared to neutral words were associated with more errors and greater key
      pressure responses. Electrophysiologically, affective processing was reflected in
      larger amplitudes to negative words in a late positive component (LPC) at the
      scalp level, and in increased activity in the pre-supplementary motor area (pre
      SMA) at the voxel level. Interestingly, an interaction between emotion and type
      of task was observed. Negative words were associated with more errors, larger
      anterior distributed LPC amplitudes and increased activity in the posterior
      cingulate cortex (PCC) in the direct compared to the indirect task. This LPC
      effect was modulated by the concreteness of the words. Finally, a task effect was
      found in a posterior negativity around 220ms, with enhanced amplitudes to words
      in the direct compared to the indirect task. The present results suggest that
      negative information contained in written language is processed irrespective of
      controlled attention is directed to it or not, but that this processing is
      reinforced in the former case. 

PMID- 24732956
TI  - Expert athletes activate somatosensory and motor planning regions of the brain
      when passively listening to familiar sports sounds.
AB  - The present functional magnetic resonance imaging study examined the neural
      response to familiar and unfamiliar, sport and non-sport environmental sounds in
      expert and novice athletes. Results revealed differential neural responses
      dependent on sports expertise. Experts had greater neural activation than novices
      in focal sensorimotor areas such as the supplementary motor area, and pre- and
      postcentral gyri. Novices showed greater activation than experts in widespread
      areas involved in perception (i.e. supramarginal, middle occipital, and calcarine
      gyri; precuneus; inferior and superior parietal lobules), and motor planning and
      processing (i.e. inferior frontal, middle frontal, and middle temporal gyri).
      These between-group neural differences also appeared as an expertise effect
      within specific conditions. Experts showed greater activation than novices during
      the sport familiar condition in regions responsible for auditory and motor
      planning, including the inferior frontal gyrus and the parietal operculum.
      Novices only showed greater activation than experts in the supramarginal gyrus
      and pons during the non-sport unfamiliar condition, and in the middle frontal
      gyrus during the sport unfamiliar condition. These results are consistent with
      the view that expert athletes are attuned to only the most familiar, highly
      relevant sounds and tune out unfamiliar, irrelevant sounds. Furthermore, these
      findings that athletes show activation in areas known to be involved in action
      planning when passively listening to sounds suggests that auditory perception of
      action can lead to the re-instantiation of neural areas involved in producing
      these actions, especially if someone has expertise performing the actions. 

PMID- 24732957
TI  - Paralog re-emergence: a novel, historically contingent mechanism in the evolution
      of antimicrobial resistance.
AB  - Evolution of resistance to drugs and pesticides poses a serious threat to human
      health and agricultural production. CYP51 encodes the target site of azole
      fungicides, widely used clinically and in agriculture. Azole resistance can
      evolve due to point mutations or overexpression of CYP51, and previous studies
      have shown that fungicide-resistant alleles have arisen by de novo mutation.
      Paralogs CYP51A and CYP51B are found in filamentous ascomycetes, but CYP51A has
      been lost from multiple lineages. Here, we show that in the barley pathogen
      Rhynchosporium commune, re-emergence of CYP51A constitutes a novel mechanism for
      the evolution of resistance to azoles. Pyrosequencing analysis of historical
      barley leaf samples from a unique long-term experiment from 1892 to 2008
      indicates that the majority of the R. commune population lacked CYP51A until
      1985, after which the frequency of CYP51A rapidly increased. Functional analysis
      demonstrates that CYP51A retains the same substrate as CYP51B, but with different
      transcriptional regulation. Phylogenetic analyses show that the origin of CYP51A
      far predates azole use, and newly sequenced Rhynchosporium genomes show CYP51A
      persisting in the R. commune lineage rather than being regained by horizontal
      gene transfer; therefore, CYP51A re-emergence provides an example of adaptation
      to novel compounds by selection from standing genetic variation. 

PMID- 24732959
TI  - Treatment of acute mixed-cell leukemia with autologous hematopoietic SCT followed
      by allogeneic hematopoietic stem cell micro-transplantation.

PMID- 24732958
TI  - Accuracy of self-reported tobacco use status among hematopoietic SCT patients.
AB  - Tobacco use is a risk factor for adverse outcomes among hematopoietic SCT (HSCT)
      patients. Accurate identification of tobacco use offers a vital opportunity to
      treat this risk factor. The current study compared self-reported tobacco use
      status with serum cotinine levels among HSCT patients at the time of pre
      transplant evaluation. A total of 444 participants completed both assessments; 44
      participants (9.9%) were classified as tobacco users with serum cotinine
      concentrations >2 ng/mL vs 29 with self-reporting. Sensitivity and specificity of
      self-reporting were 65.9% and 100%, respectively. Positive and negative
      predictive values were 100% and 96.4%, respectively. Comparing tobacco use
      documented in the medical record with cotinine, sensitivity and specificity were
      51.2% and 99.2%, respectively. Factors associated with tobacco use were male
      gender, single relationship status, less education and younger age. In summary,
      utilization of serum cotinine assays increased detection of tobacco use cases
      >50% over self-reporting. Results are discussed in the context of translation to
      care, including clinical and ethical implications, and current tobacco use
      treatment guidelines. When cotinine assays are not available, self-reporting of
      any tobacco use in the year before HSCT should trigger brief advice and cessation
      or relapse prevention counseling. 

PMID- 24732960
TI  - A novel reduced-intensity umbilical cord blood transplantation using a
      recombinant G-CSF combined with high-dose Ara-C for active myeloid malignancies.
AB  - Non-remitting patients with hematologic myeloid malignancies have poor prognosis.
      To overcome this problem, we investigated the use of reduced-intensity
      preconditioning umbilical cord blood transplantation (RICBT) combined with
      recombinant G-CSF (rG-CSF) with high-dose Ara-C, fludarabine, melphalan, and 4 Gy
      of TBI in a phase I/II study in patients with non-remitting myeloid hematologic
      malignancies. Thirteen patients were enrolled, including 12 with non-remitting
      AML and one patient with blastic crisis CML (CML-BC). The patients' median age
      was 45 years, with a median comorbidity index of 4. All patients received 4/6
      serological HLA-antigen matched unrelated umbilical cord blood. All patients were
      engrafted within 30 days after RICBT (median, 20 days; range, 14-29) and achieved
      complete remission without prior hematopoiesis. Common grade III non-hematologic
      toxicities included eight cases of transient mucositis (62%) and six cases of
      febrile neutropenia (46%). Transplant-related mortality was 7.7%. The 1-year
      overall survival was 28.6% in cases without post-RICBT treatment and 83.3% in
      cases with post-RICBT treatment. These data suggest that in active AML and CML
      BC, the combination of rG-CSF with high-dose Ara-C and fludarabine/melphalan/4 Gy
      TBI with a reduced-intensity preconditioning regimen is well tolerated, secures
      engraftment and has significant anti-leukemia activity. In addition, performing
      post-RICBT treatment may provide high-quality long-term survival and remission. 

PMID- 24732961
TI  - Corticospinal excitability preceding the grasping of emotion-laden stimuli.
AB  - Evolutionary theories posit that emotions prime organisms for action. This study
      examined whether corticospinal excitability (CSE) is modulated by the emotional
      valence of a to-be-grasped stimulus. CSE was estimated based on the amplitude of
      motor evoked potentials (MEPs) elicited using transcranial magnetic stimulation
      (TMS) and recorded on the first dorsal interosseous (FDI) muscle. Participants
      were instructed to grasp (ACTION condition) or just look at (NO-ACTION condition)
      unpleasant, pleasant and neutral stimuli. TMS pulses were applied randomly at 500
      or 250 ms before a go signal. MEP amplitudes were normalized within condition by
      computing a ratio for the emotion-laden stimuli by reference to the neutral
      stimuli. A divergent valence effect was observed in the ACTION condition, where
      the CSE ratio was higher during the preparation to grasp unpleasant compared to
      pleasant stimuli. In addition, the CSE ratio was lower for pleasant stimuli
      during the ACTION condition compared to the NO-ACTION condition. Altogether,
      these results indicate that motor preparation is selectively modulated by the
      valence of the stimulus to be grasped. The lower CSE for pleasant stimuli may
      result from the need to refrain from executing an imminent action. 

PMID- 24732962
TI  - No talking, just writing! Efficacy of an Internet-based cognitive behavioral
      therapy with exposure and response prevention in obsessive compulsive disorder.
AB  - BACKGROUND: Many patients with obsessive-compulsive disorder (OCD) do not receive
      first-line treatment according to the current guidelines (cognitive behavioral
      therapy with exposure and response prevention, CBT with ERP) due to barriers to
      treatment. Internet-based therapy is designed to overcome these barriers. The
      present study evaluates the efficacy of an Internet-based writing therapy with
      therapeutic interaction based on the concept of CBT with ERP for patients with
      OCD. METHODS: Thirty-four volunteers with OCD according to DSM-IV-criteria were
      included in the trial and randomized according to a waiting-list control design
      with follow-up measures at 8 weeks and 6 months. The intervention consisted of 14
      sessions, either starting directly after randomization or with an 8-week delay.
      Main outcome measure was the change in the severity of OCD symptoms (Yale-Brown
      Obsessive Compulsive Scale Self-Rating, Y-BOCS SR, and Obsessive-Compulsive
      Inventory-Revised, OCI-R). RESULTS: Obsessive-compulsive symptoms were
      significantly improved in the treatment group compared to the waiting-list
      control group with large effect sizes of Cohen's d = 0.82 (Y-BOCS SR) and d =
      0.87 (OCI-R), using an intention-to-treat analysis. This effect remained stable
      at 6-month follow-up. Only 4 participants (12%) dropped out prematurely from the
      study. Of the 30 completers, 90% rated their condition as improved and would
      recommend the program to their friends. CONCLUSIONS: Internet-based writing
      therapy led to a significant improvement of obsessive-compulsive symptoms. Even
      though replications with larger sample sizes are needed, the results support the
      notion that Internet-based approaches have the potential for improving the
      treatment situation for patients with OCD.

PMID- 24732963
TI  - An open-label, non-comparative, non-interventional, multi-center, post
      authorization safety study on the administration of rabeprazole to adults with
      gastro-esophageal reflux disease.
AB  - BACKGROUND: Rabeprazole produces a profound and long-lasting inhibition of
      gastric acid secretion. The aim of the study was to monitor the safety and
      efficacy of rabeprazole administered to patients with erosive or symptomatic non
      erosive reflux disease, in real-life healthcare settings. METHODS: Male and
      female patients, aged >=18 years, with endoscopy diagnosed GERD were included;
      patients received at least 8 weeks treatment with rabeprazole. Changes in
      severity of symptoms recorded on the Likert scale were analysed using marginal
      homogeneity tests. RESULTS: 186 patients were enrolled across 17 study sites; 127
      patients (68.3%) completed the study. Almost 75% of patients had an initial
      diagnosis of GERD with Grade A or B esophagitis. The most commonly reported
      adverse events (AEs) were diarrhea, flatulence, dizziness, cough, abdominal pain,
      upper abdominal pain and somnolence. Over half of AEs were unrelated to study
      drug; 1 severe AE of diarrhea was possibly related to study drug. No new AEs were
      reported not included in the current version of Summary of Product
      Characteristics. Rabeprazole was effective in reducing the symptoms of GERD; the
      Likert scale scores of symptoms decreased significantly for all patients from 0-4
      weeks and 4-8 weeks. CONCLUSIONS: In our study, rabeprazole was safe and
      effective in reducing the symptoms of GERD.

PMID- 24732964
TI  - Thymosin beta4 regulates cardiac valve formation via endothelial-mesenchymal
      transformation in zebrafish embryos.
AB  - Thymosin beta4 (TB4) has multiple functions in cellular response in processes as
      diverse as embryonic organ development and the pathogeneses of disease,
      especially those associated with cardiac coronary vessels. However, the specific
      roles played by TB4 during heart valve development in vertebrates are largely
      unknown. Here, we identified a novel function of TB4 in endothelialmesenchymal
      transformation (EMT) in cardiac valve endocardial cushions in zebrafish. The
      expressions of thymosin family members in developing zebrafish embryos were
      determined by whole mount in situ hybridization. Of the thymosin family members
      only zTB4 was expressed in the developing heart region. Cardiac valve development
      at 48 h post fertilization was defected in zebrafish TB4 (zTB4) morpholino
      injected embryos (morphants). In zTB4 morphants, abnormal linear heart tube
      development was observed. The expressions of bone morphogenetic protein (BMP) 4,
      notch1b, and hyaluronic acid synthase (HAS) 2 genes were also markedly reduced in
      atrio-ventricular canal (AVC). Endocardial cells in the AVC region were stained
      with anti-Zn5 antibody reactive against Dm-grasp (an EMT marker) to observe EMT
      in developing cardiac valves in zTB4 morphants. EMT marker expression in valve
      endothelial cells was confirmed after transfection with TB4 siRNA in the presence
      of transforming growth factor beta (TGFbeta) by RT-PCR and immunofluorescent
      assay. Zn5-positive endocardial AVC cells were not observed in zTB4 morphants,
      and knockdown of TB4 suppressed TGF-beta-induced EMT in ovine valve endothelial
      cells. Taken together, our results demonstrate that TB4 plays a pivotal role in
      cardiac valve formation by increasing EMT.1. 

PMID- 24732965
TI  - The effects of incidentally learned temporal and spatial predictability on
      response times and visual fixations during target detection and discrimination.
AB  - Responses are quicker to predictable stimuli than if the time and place of
      appearance is uncertain. Studies that manipulate target predictability often
      involve overt cues to speed up response times. However, less is known about
      whether individuals will exhibit faster response times when target predictability
      is embedded within the inter-trial relationships. The current research examined
      the combined effects of spatial and temporal target predictability on reaction
      time (RT) and allocation of overt attention in a sustained attention task.
      Participants responded as quickly as possible to stimuli while their RT and eye
      movements were measured. Target temporal and spatial predictability were
      manipulated by altering the number of: 1) different time intervals between a
      response and the next target; and 2) possible spatial locations of the target.
      The effects of target predictability on target detection (Experiment 1) and
      target discrimination (Experiment 2) were tested. For both experiments, shorter
      RTs as target predictability increased across both space and time were found. In
      addition, the influences of spatial and temporal target predictability on RT and
      the overt allocation of attention were task dependent; suggesting that effective
      orienting of attention relies on both spatial and temporal predictability. These
      results indicate that stimulus predictability can be increased without overt cues
      and detected purely through inter-trial relationships over the course of repeated
      stimulus presentations. 

PMID- 24732967
TI  - Age-related tooth wear differs between forest and savanna primates.
AB  - Tooth wear in primates is caused by aging and ecological factors. However,
      comparative data that would allow us to delineate the contribution of each of
      these factors are lacking. Here, we contrast age-dependent molar tooth wear by
      scoring percent of dentine exposure (PDE) in two wild African primate populations
      from Gabonese forest and Kenyan savanna habitats. We found that forest-dwelling
      mandrills exhibited significantly higher PDE with age than savanna yellow
      baboons. Mandrills mainly feed on large tough food items, such as hard-shell
      fruits, and inhabit an ecosystem with a high presence of mineral quartz. By
      contrast, baboons consume large amounts of exogenous grit that adheres to
      underground storage organs but the proportion of quartz in the soils where
      baboons live is low. Our results support the hypothesis that not only age but
      also physical food properties and soil composition, particularly quartz richness,
      are factors that significantly impact tooth wear. We further propose that the
      accelerated dental wear in mandrills resulting in flatter molars with old age may
      represent an adaptation to process hard food items present in their environment. 

PMID- 24732966
TI  - Effects of calorie restriction and diet-induced obesity on murine colon
      carcinogenesis, growth and inflammatory factors, and microRNA expression.
AB  - Obesity is an established colon cancer risk factor, while preventing or reversing
      obesity via a calorie restriction (CR) diet regimen decreases colon cancer risk.
      Unfortunately, the biological mechanisms underlying these associations are poorly
      understood, hampering development of mechanism-based approaches for preventing
      obesity-related colon cancer. We tested the hypotheses that diet-induced obesity
      (DIO) would increase (and CR would decrease) colon tumorigenesis in the mouse
      azoxymethane (AOM) model. In addition, we established that changes in
      inflammatory cytokines, growth factors, and microRNAs are associated with these
      energy balance-colon cancer links, and thus represent mechanism-based targets for
      colon cancer prevention. Mice were injected with AOM once a week for 5 weeks and
      randomized to: 1) control diet; 2) 30% CR diet; or 3) DIO diet. Mice were
      euthanized at week 5 (n = 12/group), 10 (n = 12/group), and 20 (n = 20/group)
      after the last AOM injection. Colon tumors were counted, and cytokines, insulin
      like growth factor 1 (IGF-1), IGF binding protein 3 (IGFBP-3), adipokines,
      proliferation, apoptosis, and expression of microRNAs (miRs) were measured. The
      DIO diet regimen induced an obese phenotype (~36% body fat), while CR induced a
      lean phenotype (~14% body fat); controls were intermediate (~26% body fat).
      Relative to controls, DIO increased (and CR decreased) the number of colon tumors
      (p = 0.01), cytokines (p<0.001), IGF-1 (p = 0.01), and proliferation (p<0.001).
      DIO decreased (and CR increased) IGFBP-3 and apoptosis (p<0.001). miRs including
      mir-425, mir-196, mir-155, mir-150, mir-351, mir-16, let-7, mir34, and mir-138
      were differentially expressed between the dietary groups. We conclude that the
      enhancing effects of DIO and suppressive effects of CR on colon carcinogenesis
      are associated with alterations in several biological pathways, including
      inflammation, IGF-1, and microRNAs. 

PMID- 24732968
TI  - Genome-wide transcriptional profiling of skin and dorsal root ganglia after
      ultraviolet-B-induced inflammation.
AB  - Ultraviolet-B (UVB)-induced inflammation produces a dose-dependent mechanical and
      thermal hyperalgesia in both humans and rats, most likely via inflammatory
      mediators acting at the site of injury. Previous work has shown that the gene
      expression of cytokines and chemokines is positively correlated between species
      and that these factors can contribute to UVB-induced pain. In order to
      investigate other potential pain mediators in this model we used RNA-seq to
      perform genome-wide transcriptional profiling in both human and rat skin at the
      peak of hyperalgesia. In addition we have also measured transcriptional changes
      in the L4 and L5 DRG of the rat model. Our data show that UVB irradiation
      produces a large number of transcriptional changes in the skin: 2186 and 3888
      genes are significantly dysregulated in human and rat skin, respectively. The
      most highly up-regulated genes in human skin feature those encoding cytokines
      (IL6 and IL24), chemokines (CCL3, CCL20, CXCL1, CXCL2, CXCL3 and CXCL5), the
      prostanoid synthesising enzyme COX-2 and members of the keratin gene family.
      Overall there was a strong positive and significant correlation in gene
      expression between the human and rat (R = 0.8022). In contrast to the skin, only
      39 genes were significantly dysregulated in the rat L4 and L5 DRGs, the majority
      of which had small fold change values. Amongst the most up-regulated genes in DRG
      were REG3B, CCL2 and VGF. Overall, our data shows that numerous genes were up
      regulated in UVB irradiated skin at the peak of hyperalgesia in both human and
      rats. Many of the top up-regulated genes were cytokines and chemokines,
      highlighting again their potential as pain mediators. However many other genes
      were also up-regulated and might play a role in UVB-induced hyperalgesia. In
      addition, the strong gene expression correlation between species re-emphasises
      the value of the UVB model as translational tool to study inflammatory pain. 

PMID- 24732969
TI  - The nephrotoxic Ifosfamide-metabolite chloroacetaldehyde interferes with renal
      extracellular matrix homeostasis.
AB  - BACKGROUND/AIMS: Chronic renal proximal tubule dysfunction after therapy with the
      antineoplastic agent ifosfamide (IFO) is often attributed to the metabolite
      chloroacetaldehyde (CAA). Chronic IFO-nephropathy is reported to result in
      tubulointerstitial fibrosis and inflammation. METHODS: To elucidate possible
      effects of CAA on extracellular matrix homeostasis, we investigated the action of
      CAA on markers of extracellular matrix (ECM) homeostasis in human proximal tubule
      cells (RPTEC) by use of direct ELISA for extracellular collagens and gelatin
      zymography. RESULTS: An increase in type III collagen and a decrease in type IV
      collagen abundance in the media of RPTEC could be observed after exposure to CAA
      in clinically relevant concentrations. CAA increased intracellular type III and
      decreased intracellular type IV collagen. MMP-2 activity was decreased but MMP-9
      activity unchanged. The enhanced CAA-induced collagen III formation could be
      attenuated by the intracellular Ca(2+)-chelator BAPTA-AM, the PKA-antagonist H-89
      and by extracellular acidification. CAA-induced collagen III abundance was
      enhanced by db-cAMP and IBMX and by protein overload. CONCLUSIONS: CAA exerts
      profibrotic effects on RPTEC dependent on Ca(2+) and cAMP/PKA-signaling. These
      effects are enhanced by additional protein burden and attenuated by
      acidification. (c) 2014 S. Karger AG, Basel.

PMID- 24732971
TI  - Metabolism. Cilia length--role in energy balance.

PMID- 24732970
TI  - Transcutaneous electrical nerve stimulation regulates organ blood flow and
      apoptosis during controlled hypotension in dogs.
AB  - Transcutaneous electrical nerve stimulation (TENS) is commonly used in clinical
      practice for alleviating pains and physiological disorders. It has been reported
      that TENS could counteract the ischemic injury happened in some vital organs. To
      determine the protective effect of TENS on internal organs during CH in dogs,
      target hypotension was maintained for 60 min at 50% of the baseline mean arterial
      pressure (MAP). The perfusion to the brain, liver, stomach, and kidney was
      recorded and apoptosis within these organs was observed. Results showed that when
      arriving at the target MAP, and during the maintaining stage for 10 min,
      perfusion to the stomach and liver in the CH+TENS group was much higher than in
      the CH group (P<0.05). Perfusion to the cerebral cortex greatly declined in both
      the controlled pressure groups when compared with the general anesthesia (GA)
      group (P<0.05). After withdrawing CH, the hepatic blood flow in both the CH and
      CH+TENS groups, and the gastric and cerebral cortical blood flow in the CH+TENS
      group, were rapidly increased. By the end of MAP restoration, gastric blood flow
      in the CH group was still low. At 72 h after applying CH, terminal
      deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL)
      positive cells in stomach and kidney tissue from the CH group were significantly
      increased compared with those in the GA group (P<0.05). There was no significant
      difference in TUNEL-positive cells in the liver and hippocampus among the three
      groups. Our results demonstrated that CH with a 50% MAP level could cause lower
      perfusion to the liver, stomach, cerebral cortex, and kidney, with apoptosis
      subsequently occurring in the stomach and kidney. TENS combined GA is able to
      improve the blood flow to the liver, stomach, and reduce the apoptosis in the
      stomach and kidney. 

PMID- 24732972
TI  - Diabetes. Attenuated incretin effect after glucose loading in monogenic HNF1A
      diabetes.

PMID- 24732973
TI  - Obesity. Copy number variants in AMY1 connected with obesity via carbohydrate
      metabolism.

PMID- 24732975
TI  - Evaluation of prostate-specific antigen isoform p2PSA and its derivates, %p2PSA,
      prostate health index and prostate dimension-adjusted related index in the
      detection of prostate cancer at first biopsy: an exploratory, prospective study.
AB  - OBJECTIVE: To confirm the accuracy of serum proPSA (p2PSA) and its derivatives,
      percentage of p2PSA to free PSA (%p2PSA) and Prostate Health Index (PHI) and to
      test the value of prostate dimension-adjusted related index p2PSA density
      (p2PSAD), %p2PSA density (%p2PSAD) and PHI density (PHID) in discriminating
      between patients with and without prostate cancer (PCa). PATIENTS AND METHODS:
      This is a prospective cohort study of 275 patients with a total PSA (tPSA) of 2
      10 ng/ml who underwent initial prostate biopsy. Multivariate logistic regression
      models were complemented by predictive accuracy analysis. RESULTS: PCa was
      diagnosed in 31.2% of subjects. Median tPSA did not differ between groups, while
      PSA density (PSAD), percent free PSA (%fPSA), p2PSA, %p2PSA, PHI, p2PSAD, %p2PSAD
      and PHID (all p < 0.05) were different between men with and without PCa.
      Univariate accuracy analysis showed p2PSAD (area under the receiver-operating
      characteristic curve [AUC]: 0.71), %p2PSAD (AUC: 0.76) and PHID (AUC: 0.77) to be
      the most accurate predictors of PCa at biopsy, significantly outperforming tPSA
      (AUC: 0.54), PSAD (AUC: 0.68) and %fPSA (AUC: 0.59) (p <= 0.001). At multivariate
      logistic regression models, p2PSAD and PHID significantly increased the accuracy
      of the basal multivariate model (all p < 0.01). At 90% specificity, sensitivity
      for p2PSAD, %p2PSAD and PHID were 33.7, 43 and 40.7%, respectively. Spearman's
      rho coefficient analysis demonstrated a significant relationship between Gleason
      score, %p2PSA (r = 0.216, p = 0.046), PHI (r = 0.223, p = 0.039) and %p2PSAD (r =
      0.205, p = 0.05). CONCLUSIONS: Considering patients suited for initial prostate
      biopsy by a tPSA range of 2-10 ng/ml, PSA isoforms were confirmed to be strong
      predictors of PCa. The prostate dimension-adjusted PSA isoforms have been shown
      to differentiate between patients with or without PCa, with an AUC of 0.71-0.77,
      p2PSAD offering a gain in accuracy with respect to tPSA, %fPSA and PSAD.

PMID- 24732976
TI  - High performance polymer solar cells with as-prepared zirconium acetylacetonate
      film as cathode buffer layer.
AB  - Low-work-function active metals are commonly used as cathode in polymer solar
      cells (PSCs), but sensitivity of the active metals towards moisture and oxygen
      results in poor stability of the devices. Therefore, solution-proceessable and
      stable cathode buffer layer is of great importance for the application of PSCs.
      Here we demonstrate high performance PSCs by employing as-prepared zirconium
      acetylacetonate (a-ZrAcac) film spin-cast from its ethanol solution as cathode
      buffer layer. The PSCs based on a low bandgap polymer PBDTBDD as donor and PC60BM
      as acceptor with a-ZrAcac/Al cathode demonstrated an average power conversion
      efficiency (PCE) of 8.75% which is significantly improved than that of the
      devices with traditional Ca/Al cathode. The improved photovoltaic performance is
      benefitted from the decreased series resistance and enhanced light harvest of the
      PSCs with the a-ZrAcac/Al cathode. The results indicate that a-ZrAcac is a
      promising high performance cathode buffer layer for fabricating large area
      flexible PSCs. 

PMID- 24732977
TI  - Does physical exercise help maintain mental health during pregnancy? A comparison
      of changes in mental health in participants of physical exercise classes and
      childbirth classes.
AB  - BACKGROUND: This study aims to compare the changes in the negative indices of
      mental health in pregnant women who participated in programs of either physical
      exercise classes or childbirth classes. METHODS: The study was quasi-experimental
      in nature and run on 109 healthy primigravidae aged from 22 to 37, including 62
      women participating in an exercise program (exercise group, E-group) for pregnant
      women and 47 women attending traditional childbirth classes (childbirth classes
      group, CC-group). The mental health assessment was performed using Goldberg's
      General Health Questionnaire (GHQ-28). RESULTS: The negative indices of mental
      health did not change over time. Lower levels of somatic symptoms and severe
      depression, as well as total score, were observed in the E-group (condition
      effect). Time * condition interactions, as well as analysis of change within the
      groups, indicated that in the CC-group all indices of disorders increased
      significantly, whereas in the E-group, only the increase of depression was
      significant. CONCLUSIONS: Regular physical exercises during pregnancy may
      constitute a factor in the prophylaxis of mental health disorders in pregnant
      women.

PMID- 24732974
TI  - The pathophysiology of hypertension in patients with obesity.
AB  - The combination of obesity and hypertension is associated with high morbidity and
      mortality because it leads to cardiovascular and kidney disease. Potential
      mechanisms linking obesity to hypertension include dietary factors, metabolic,
      endothelial and vascular dysfunction, neuroendocrine imbalances, sodium
      retention, glomerular hyperfiltration, proteinuria, and maladaptive immune and
      inflammatory responses. Visceral adipose tissue also becomes resistant to insulin
      and leptin and is the site of altered secretion of molecules and hormones such as
      adiponectin, leptin, resistin, TNF and IL-6, which exacerbate obesity-associated
      cardiovascular disease. Accumulating evidence also suggests that the gut
      microbiome is important for modulating these mechanisms. Uric acid and altered
      incretin or dipeptidyl peptidase 4 activity further contribute to the development
      of hypertension in obesity. The pathophysiology of obesity-related hypertension
      is especially relevant to premenopausal women with obesity and type 2 diabetes
      mellitus who are at high risk of developing arterial stiffness and endothelial
      dysfunction. In this Review we discuss the relationship between obesity and
      hypertension with special emphasis on potential mechanisms and therapeutic
      targeting that might be used in a clinical setting. 

PMID- 24732979
TI  - Recent advances in thermal treatment techniques and thermally induced immune
      responses against cancer.
AB  - In the past decades, techniques for tumor diagnosis and treatment have been
      significantly advanced. However, the five-year survival rate of cancer patients
      remains low. New modalities are highly desirable based on technology innovation
      and translational medicine. In this paper, recent outcomes of thermal ablation
      techniques are reviewed, including thermal energy delivery methods, thermally
      induced immune responses in depth. It is suggested that the synergy of local
      thermal ablation and thermally induced whole body immune response could be a
      promising direction for effective cancer therapy in the near future, especially
      for highly metastatic tumor. 

PMID- 24732978
TI  - pix-1 controls early elongation in parallel with mel-11 and let-502 in
      Caenorhabditis elegans.
AB  - Cell shape changes are crucial for metazoan development. During Caenorhabditis
      elegans embryogenesis, epidermal cell shape changes transform ovoid embryos into
      vermiform larvae. This process is divided into two phases: early and late
      elongation. Early elongation involves the contraction of filamentous actin
      bundles by phosphorylated non-muscle myosin in a subset of epidermal (hypodermal)
      cells. The genes controlling early elongation are associated with two parallel
      pathways. The first one involves the rho-1/RHOA-specific effector let-502/Rho
      kinase and mel-11/myosin phosphatase regulatory subunit. The second pathway
      involves the CDC42/RAC-specific effector pak-1. Late elongation is driven by
      mechanotransduction in ventral and dorsal hypodermal cells in response to body
      wall muscle contractions, and involves the CDC42/RAC-specific Guanine-nucleotide
      Exchange Factor (GEF) pix-1, the GTPase ced-10/RAC and pak-1. In this study, pix
      1 is shown to control early elongation in parallel with let-502/mel-11, as
      previously shown for pak-1. We show that pix-1, pak-1 and let-502 control the
      rate of elongation, and the antero-posterior morphology of the embryos. In
      particular, pix-1 and pak-1 are shown to control head, but not tail width, while
      let-502 controls both head and tail width. This suggests that let-502 function is
      required throughout the antero-posterior axis of the embryo during early
      elongation, while pix-1/pak-1 function may be mostly required in the anterior
      part of the embryo. Supporting this hypothesis we show that low pix-1 expression
      level in the dorsal-posterior hypodermal cells is required to ensure high
      elongation rate during early elongation. 

PMID- 24732983
TI  - The importance of nursing a healthy reputation.

PMID- 24732980
TI  - Vibrio vulnificus phage PV94 is closely related to temperate phages of V.
      cholerae and other Vibrio species.
AB  - BACKGROUND: Vibrio vulnificus is an important pathogen which can cause serious
      infections in humans. Yet, there is limited knowledge on its virulence factors
      and the question whether temperate phages might be involved in pathogenicity, as
      is the case with V. cholerae. Thus far, only two phages (SSP002 and VvAW1)
      infecting V. vulnificus have been genetically characterized. These phages were
      isolated from the environment and are not related to Vibrio cholerae phages. The
      lack of information on temperate V. vulnificus phages prompted us to isolate
      those phages from lysogenic strains and to compare them with phages of other
      Vibrio species. RESULTS: In this study the temperate phage PV94 was isolated from
      a V. vulnificus biotype 1 strain by mitomycin C induction. PV94 is a myovirus
      whose genome is a linear double-stranded DNA of 33,828 bp with 5'-protruding
      ends. Sequence analysis of PV94 revealed a modular organization of the genome.
      The left half of the genome comprising the immunity region and genes for the
      integrase, terminase and replication proteins shows similarites to V. cholerae
      kappa phages whereas the right half containing genes for structural proteins is
      closely related to a prophage residing in V. furnissii NCTC 11218. CONCLUSION: We
      present the first genomic sequence of a temperate phage isolated from a human V.
      vulnificus isolate. The sequence analysis of the PV94 genome demonstrates the
      wide distribution of closely related prophages in various Vibrio species.
      Moreover, the mosaicism of the PV94 genome indicates a high degree of horizontal
      genetic exchange within the genus Vibrio, by which V. vulnificus might acquire
      virulence-associated genes from other species.

PMID- 24732982
TI  - Private-sector management solutions.

PMID- 24732981
TI  - Favorable outcomes for both mother and baby are possible in pregnant women with
      Crimean-Congo hemorrhagic fever disease: a case series and literature review.
AB  - To assess the impact of Crimean-Congo hemorrhagic fever (CCHF) infection during
      pregnancy on maternal and fetal outcomes, we present the clinical and laboratory
      findings and outcomes of 5 pregnant women with CCHF infection as well as fetal
      outcomes. We also reviewed previously reported cases with CCHF infection in
      pregnant women. All pregnant women with CCHF infection who had been hospitalized
      between August 2007 and September 2011 were included. The gestational ages at the
      time of CCHF infection were 8, 18, 20, 21 and 32 weeks. CCHF infection was
      acquired during the 1st trimester in only 1 case and resulted in spontaneous
      abortion. The other 4 pregnant women completely recovered, all reached a healthy
      full-term gestation and 4 term babies were born. All infants had normal birth
      weight and were found to be healthy on their first examination and follow-up. In
      the literature concerning CCHF infection in pregnancy, 8 published articles
      including case reports or case series and 1 poster presentation including 1 case
      could be accessed. In conclusion, there is a risk of vertical transmission of
      CCHF infection, and infections acquired early in gestation had a poor prognosis
      for the fetus.

PMID- 24732984
TI  - Breaking through the culture of fear in dementia care.

PMID- 24732985
TI  - Confirming nasogastric tube position with electromagnetic tracking versus pH or X
      ray and tube radio-opacity.
AB  - Recent evidence suggests official statistics greatly underestimate the occurrence
      of complications from misplaced nasogastric (NG) tubes, even when detected.
      Current methods of confirming tube position do not provide adequate protection
      from misplacement. In addition, some tubes are inadequately radio-opaque. We
      prospectively audited placement of Cortrak polyurethane tubes (PUTs) to
      determine: accuracy of the electromagnetic (EM) trace in confirming tube
      position, radio-opacity of PUTs compared with previously placed polyvinylchloride
      (PVC) Ryles tubes and whether 12 French PUTs can be used to aspirate gastric
      residual volumes (GRVs). A total of 127 PUTs were placed in 113 patients. EM
      traces accurately confirmed tube position compared with X-ray (100% agreement). A
      'gastric' EM trace has been defined for future use by other operators. PUTs were
      adequately radio-opaque with good agreement between interpreters (>98%) whereas
      PVC Ryles tubes were insufficiently radio-opaque (57-73%), invisible in 23% of
      cases and with poor agreement between interpreters leaving risk of error. The
      alternative of using pH confirmation was not possible in 44%. In these cases
      subsequent X-ray incurred a 2-hour delay to feed and medicines. In addition,
      neither post-placement pH testing nor X-ray warn of lung placement and potential
      trauma, whereas the EM trace warned of lung placement prior to damage in 7% of
      placements. 12 French, single-port PUTs appear adequate to aspirate large GRVs.
      EM tracing may be considered a standalone method of confirming NG tube position.
      Corflo (Cortrak) PUTs are adequately radio-opaque. Use of PVC Ryles and other
      inadequately radio-opaque tubes should stop.

PMID- 24732986
TI  - Five by five: the joys of placements.

PMID- 24732987
TI  - Problems with use of a Foley catheter in enteral tube feeding.
AB  - This article discusses the unlicensed use of a Foley catheter in home enteral
      tube feeding in the community. It is now clear that patients on long-term enteral
      feeding in the community may require replacement of their feeding tubes due to
      deterioration, damage or tube dislodgment. Often, these conventional feeding
      tubes such as percutaneous endoscopic gastrostomy and radiologically inserted
      gastrostomy tubes are replaced with similar tubes or with balloon gastrostomy
      tubes. However, the use of a Foley catheter in place of conventional feeding
      tubes as replacement tube has been observed in a number of patients in practice
      and documented in literature. The Foley catheter is significantly less expensive
      and easily accessible than conventional feeding tubes or balloon gastrostomy
      tubes. However, its use as an enteral feeding tube has implications for practice
      in terms of its use as unlicensed product, consent, ethics and professional
      responsibilities. Issues relating to body image and quality of life are also
      discussed. 

PMID- 24732988
TI  - Embedding the 6 Cs into clinical research practice and management.
AB  - The White Paper, Equity and Excellence:liberating the NHS (DH, 2010) emphasises
      the promotion and conduct of research as a core NHS role. The updated NHS
      Constitution(DH, 2013) outlines its commitment to innovation and also to the
      promotion and conduct of research to improve the current and future health and
      social care of the population.Furthermore, NHS England (2013) in its guidance,
      Everyone Counts: planning for patients 2014/15 to 2018/19, identified research as
      one of the essential elements for a successful and sustainable health economy
      recommending research and evaluation be embedded across the whole patient
      pathway.The 6 Cs were launched in 2012 to drive the Compassion in Practice vision
      with calls for every nurse, midwife and member of the care team to implement them
      into practice (NHS Commissioning Board, 2013). The 6 Cs can be embedded into the
      world of clinical research so that research patients are afforded the same levels
      of compassionate care by all members of the research workforce and, indeed, to
      drive compassion in practice for the researchers themselves. It is suggested that
      this will result in high quality, compassionate personalised care for all and
      that the biggest voices will be those of the patients themselves.

PMID- 24732989
TI  - What are the barriers to spiritual care in a hospital setting?
AB  - Spiritual care is a vital component of care that is given to patients by health
      professionals in order to prevent poor health and treat illness. It is
      fundamental to patients' wellbeing and nurses' integrity that nurses carry out
      their care in a holistic manner and meet patients' spiritual needs. However, a
      number of studies show that health professionals are failing to meet patients'
      spiritual needs while in hospital. Nurses are unable to fulfil patients'
      spiritual needs for a variety of reasons. The main barriers to spiritual care are
      the difficulty in defining spirituality; the lack of clear guidelines for the
      nurse's role in providing spiritual care; nurses' lack of time to provide
      spiritual care; and a lack of training and education on spirituality for pre- and
      post-registration nurses. 

PMID- 24732990
TI  - Nursing in universities: does it matter?

PMID- 24732991
TI  - Patient journeys: diagnosis and treatment of pernicious anaemia.
AB  - BACKGROUND: Instigating a patient support group for patients with pernicious
      anaemia (PA) revealed dissatisfaction with its current diagnosis and treatment.
      The authors investigated the clinical features, patient experience of diagnosis
      and treatment of PA in the UK. METHODS: A total of 889 patients registered with
      the PA Society support group completed an online survey or postal questionnaire.
      Outcome measures included clinical features, length of time to diagnosis and
      patient satisfaction with current treatment RESULTS: One-third of patients
      experienced symptoms for up to 1 year before diagnosis; 14% waited more than 10
      years for a diagnosis. Neurological features were highly prevalent, the most
      common being memory loss and poor concentration. Nearly two-thirds of respondents
      were dissatisfied with current treatment; 10% used a non-licensed form of B12 to
      supplement their prescribed injections. CONCLUSION: The diagnosis and treatment
      of PA should be subject to a thorough review. This article discusses the patient
      survey and results and makes recommendations for how the diagnosis and treatment
      of PA may be evaluated.

PMID- 24732992
TI  - Oxygen therapy: professional compliance with national guidelines.
AB  - One of the major causes of critical illness in the UK is the deterioration of
      respiratory function (British Thoracic Society (BTS), 2008). The administration
      of supplemental oxygen therapy, although often lifesaving, can also have serious
      consequences if performed inappropriately. A literature review was carried out to
      establish whether oxygen therapy was prescribed and administered in acute care in
      accordance with both national guidelines and local policy. Four common themes
      were identified from the literature: prescribing, monitoring, administration and
      equipment. The review suggests that an educational programme ranging from pre
      registration curriculum content to the practical experiences of junior doctors
      with regard to oxygen management would be appropriate. The authors suggest that
      the current practice of healthcare practitioners should undergo a planned
      timetable of audit to improve the prescription, administration and monitoring of
      supplemental oxygen therapy for the benefit of patient outcomes. 

PMID- 24732993
TI  - Reducing anxiety in preoperative patients: a systematic review.
AB  - There are still uncertainties regarding the appropriateness and effectiveness of
      various modes of delivering preoperative education. Hence, this systematic review
      was conducted to investigate the effectiveness of various preoperative
      educational interventions in reducing preoperative anxiety. Fourteen
      interventional trials (12 randomised controlled trials and two pre/post test
      trials) involving a total of 1752 participants were included in the review. Four
      studies used audiovisual; two trials used visual; two trials used multimedia
      supported education; one trial used a website; two trials involved verbal
      education delivered by a psychologist or a nurse facilitator coupled with
      leaflets; and one trial involved informational leaflets only. Eight of the 14
      trials demonstrated that preoperative education intervention reduced preoperative
      anxiety significantly (P<0.05). It can be concluded that preoperative education
      interventions are promising in reducing preoperative anxiety in patients
      scheduled for surgical procedures. 

PMID- 24732994
TI  - New nursing apprenticeship schemes to be introduced.

PMID- 24732995
TI  - Patient safety: a view from across The Pond.

PMID- 24732996
TI  - Reflection: from staff nurse to nurse consultant. Part 5: reflective practice.

PMID- 24732997
TI  - Paper-light working in nursing.

PMID- 24732998
TI  - The Illness Experiences of Women with Overactive Bladder in Hong Kong.
AB  - Overactive bladder (OAB) is a common chronic bladder dysfunction worldwide.
      However, the illness experiences of women with OAB in Asian countries have not
      been well documented. In this article, I investigate the illness experiences of
      women with OAB in Hong Kong. I adopted a qualitative study design by conducting
      30 in-depth, semistructured interviews with women who were diagnosed as having
      OAB and were aged between 28 and 55 years. Negative illness experiences were
      noted among the participants, including embarrassment, shame, frustration,
      helplessness, resignation, uselessness, and self-seclusion. These negative
      experiences were not only the result of the physical symptoms and limitations
      brought on by the bladder condition, but were also caused by social difficulties
      such as the flippant attitudes of primary care providers, the tortuous journey of
      seeking and receiving treatment, and a lack of understanding from social members
      such as family members and colleagues in the workplace.

PMID- 24732999
TI  - Older People's Perceptions of Remaining Physically Active and Living With Chronic
      Pain.
AB  - Active aging, using the conventional sense of activity, might be difficult to
      achieve for people with chronic musculoskeletal pain (CMP). Given that a large
      number of older people will develop CMP, it is important to consider a broader
      conceptualization of activity and how this might fit into discourses of aging. We
      report findings from a study of the experiences of chronic pain in the daily life
      of 60 older people. In this article we focus on the role and meanings of physical
      activity for those older people. We develop a typology of styles-deliberate,
      strategic, and natural-to show how people approached physical activity and how
      its meaning differed for individuals in different contexts and across their life
      course. We suggest a more balanced perspective of aging in which "slowing down"
      might also be a desirable outcome for some older people with CMP but is not
      incompatible with well-being.

PMID- 24733000
TI  - Unenhanced respiratory-gated magnetic resonance angiography (MRA) of renal artery
      in hypertensive patients using true fast imaging with steady-state precession
      technique compared with contrast-enhanced MRA.
AB  - OBJECTIVE: This study was aimed to evaluate the accuracy of "True Fast Imaging
      with Steady-State Precession" (TrueFISP) MR angiography (MRA) for diagnosis of
      renal arterial stenosis (RAS) in hypertensive patients. METHODS: Twenty-two
      patients underwent both TrueFISP MRA and contrast-enhanced MRA (CE-MRA) on a 1.5
      T MR imager. Volume of main renal arteries, length of maximal visible renal
      arteries, number of visualized branches, stenotic grade, and subjective quality
      were compared. Paired 2-tailed Student t test and Wilcoxon signed rank test were
      applied to evaluate the significance of these variables. RESULTS: Volume of main
      renal arteries, length of maximal visible renal arteries, and number of branches
      indicated no significant difference between the 2 techniques (P > 0.05). Stenotic
      degree of 10 RAS was greater on CE-MRA than on TrueFISP MRA. Qualitative scores
      from TrueFISP MRA were higher than those from CE-MRA (P < 0.05). CONCLUSIONS:
      TrueFISP MRA is a reliable and accurate method for evaluating RAS.

PMID- 24733001
TI  - The long-lasting effect of ferumoxytol on abdominal magnetic resonance imaging.
AB  - Ferumoxytol is a parenteral iron therapy that the Food and Drug Administration
      recently approved for the treatment of iron-deficiency anemia. The form of the
      iron, ultrasmall superparamagnetic iron oxide nanoparticles, causes T1, T2, and
      T2* shortening on magnetic resonance imaging, which can mimic hemosiderosis. We
      report such a case, with laboratory findings that demonstrate normal iron stores,
      and discuss the potential implications. 

PMID- 24733002
TI  - Preoperative T staging of gastric cancer: comparison of diffusion- and T2
      weighted magnetic resonance imaging.
AB  - OBJECTIVE: The objective of our study was to assess the clinical feasibility of
      diffusion-weighted (DW) magnetic resonance (MR) imaging in preoperative T staging
      of gastric cancer prospectively. METHODS: Forty-five patients underwent axial T2
      weighted (T2W) and DW (b, 0 and 1000 seconds/mm) MR imaging. Two radiologists
      interpreted the images for detection and staging of the tumors independently. The
      McNemar test was used to check differences in diagnostic accuracy with the
      reference of postoperative histopathological results. RESULTS: Diffusion-weighted
      and T2W images detected 44 and 42 of 45 histologically confirmed lesions,
      respectively. Furthermore, DW images detected 11 of 12 pT1 lesions compared to 9
      of 12 lesions by T2W images. The staging accuracy of advanced gastric cancer
      (>=pT2) in DW imaging is significantly higher than that in T2W imaging (87.9% and
      69.7%, respectively; P < 0.05). CONCLUSIONS: Diffusion-weighted is superior to
      T2W imaging in detection of early gastric cancers (pT1) and staging advanced
      cancers (>=pT2).

PMID- 24733003
TI  - Pulmonary hypertension detection using dynamic and static measurable parameters
      on CT angiography.
AB  - OBJECTIVE: The aim was to assess dynamic and static parameters on routine
      computed tomography pulmonary angiography (CTPA) that may detect pulmonary
      hypertension (PH). METHODS: Fifty patients underwent CTPA and echocardiograms.
      Twenty-six patients had PH, and 24 patients did not have PH. The following
      parameters were measured on CTPA: density of the pulmonary artery (PA), ratio
      between the density in the PA and the thoracic aorta (TA), the time between the
      start of contrast injection to the time the scan trigger density was reached, and
      PA diameter. RESULTS: All measured parameters showed significant correlation with
      PH detected by echocardiogram. The best combination of parameters for detection
      of PH was contrast density ratio between PA and thoracic aorta of greater than or
      equal to 1.5 and/or a time to scan trigger of greater than or equal to 8 seconds.
      CONCLUSIONS: The parameters measured correlate well with PH by echocardiography.
      This suggests that CTPA can potentially be used to detect PH.

PMID- 24733004
TI  - Multiparametric magnetic resonance imaging of the prostate aids detect lesion
      progression.
AB  - Multiparametric magnetic resonance imaging (MRI) provides an accurate anatomical
      assessment of the tumor and its local staging. Herein, we report a case of
      intermediate-risk prostatic adenocarcinoma, initially followed on active
      surveillance, which upgraded from Gleason 7 (3 + 4) to Gleason 8 (4 + 4) on
      transrectal ultrasound/MRI fusion biopsy after progression of MR spectroscopic
      findings and review of the role of multiparametric MRI in the follow-up of
      patients with prostate cancer undergoing active surveillance. 

PMID- 24733005
TI  - Intravoxel incoherent motion (IVIM) diffusion imaging in prostate cancer - what
      does it add?
AB  - OBJECTIVE: To compare 2 previously presented algorithms for extracting parameters
      from intravoxel incoherent motion (IVIM) studies and investigate them in the
      context of tissue differentiation. METHODS: Magnetic resonance imaging (MRI) was
      performed in 23 patients without histologically proven prostate carcinoma (PCa)
      and 27 patients with histologically proven PCa. Two methods were used to
      determine IVIM parameters (f, D, D*). Receiver operating characteristic analysis
      was performed for IVIM parameters and apparent diffusion coefficient for
      discrimination of prostate tissue. RESULTS: The IVIM parameters showed no
      significant difference between patients without PCa and normal areas in patients
      with PCa (r = 0.46-0.99). Results for D were not significantly different for both
      methods (P = 0.22), whereas f from method 1 was significantly higher than the f
      from method 2 (P < 0.05). The diffusion parameters D (both methods) and apparent
      diffusion coefficient could discriminate between tumor and normal areas (receiver
      operating characteristic analysis, area under the curve, >=0.90). Additionally,
      in subgroup analysis, only D was able to discriminate between low- and high-grade
      PCa. CONCLUSIONS: For tumor detection, IVIM diffusion does not yield a clear
      added value, but the perfusion-free diffusion constant D may hold potential for
      improved image-based tumor grading.

PMID- 24733006
TI  - The medial synovial fold of the posterior cruciate ligament: cadaveric
      investigation together with magnetic resonance imaging and histology.
AB  - OBJECTIVE: The purposes of our study were to analyze magnetic resonance imaging
      (MRI) and cadaveric findings concerning the medial synovial fold of the posterior
      cruciate ligament (PCL) and to classify the types of fold according to anatomic
      location. METHODS: Two musculoskeletal radiologists reviewed MR images of 17
      cadaveric knees to classify the types of medial fold of the PCL by consensus. The
      MRI types were divided into 3 groups. In type A, there was no definitive medial
      fold; and in type B, inferior-short type, there was a small protrusion of the
      medial border. Type C, inferior-long type, had a long enough fold to exceed the
      imaginary line, which is connecting between the medial tibial condyle and
      posterolateral aspect of the medial femoral condyle. Correlations were sought
      between the findings derived from the MRI studies and cadaveric dissections.
      Histologic analyses of the medial fold were also performed. RESULTS: On MRI, the
      most common type of medial fold was type B (76.4%), followed by type C (11.8%)
      and type A (11.8%). In the cadaveric investigation, the medial folds of both
      types B and C were found to project into the medial femorotibial joint. Moreover,
      there was also a protruding medial fold at the superior aspect of the PCL in the
      A. Histologic examination of the medial folds revealed collagenous tissue
      surrounded by synovial cells. CONCLUSIONS: Medial folds of the PCL are normal
      synovial structures that can be seen by MRI and in cadaveric studies in a large
      proportion of the population.

PMID- 24733008
TI  - pH-dependent drug-drug interactions for weak base drugs: potential implications
      for new drug development.
AB  - Absorption of an orally administered drug with pH-dependent solubility may be
      altered when it is coadministered with a gastric acid-reducing agent (ARA).
      Assessing a drug's potential for pH-dependent drug-drug interactions (DDIs),
      considering study design elements for such DDI studies, and interpreting and
      communicating study results in the drug labeling to guide drug dosing are
      important for drug development. We collected pertinent information related to new
      molecular entities approved from January 2003 to May 2013 by the US Food and Drug
      Administration for which clinical DDI studies with ARAs were performed. On the
      basis of assessments of data on pH solubility and in vivo DDIs with ARAs, we
      proposed a conceptual framework for assessing the need for clinical pH-dependent
      DDI studies for weak base drugs (WBDs). Important study design considerations
      include selection of ARAs and timing of dosing of an ARA relative to the WBD in a
      DDI study. Labeling implications for drugs having DDIs with ARAs are also
      illustrated.

PMID- 24733007
TI  - Association of CHRNA5-A3-B4 SNP rs2036527 with smoking cessation therapy response
      in African-American smokers.
AB  - Associations between CHRNA5-A3-B4 variants and smoking behaviors exist; however,
      the association with smoking abstinence is less understood, particularly that
      among African Americans. In 1,295 African Americans enrolled in two clinical
      trials, we investigated the association between CHRNA5-A3-B4 and smoking
      abstinence. The rs2056527(A) allele was associated with lower abstinence with
      active pharmacotherapy (during treatment: odds ratio (OR) = 0.42, P < 0.001; end
      of treatment (EOT): OR = 0.55, P = 0.004), or with nicotine gum alone (during
      treatment: OR = 0.31, P < 0.001; EOT: OR = 0.51, P = 0.02), but not significantly
      with bupropion, although similar directions and magnitudes were observed (during
      treatment: OR = 0.54, P = 0.05; EOT: OR = 0.59, P = 0.08). In addition, the
      rs588765(T) allele was associated with abstinence with gum during treatment (OR =
      2.31, P < 0.01). The SNP rs16969968 occurred at a low frequency and was not
      consistently associated with abstinence. CHRNA5-A3-B4 variants were not
      associated with tobacco consumption, and adjustments for smoking behaviors did
      not alter the associations with smoking abstinence. Together, our data suggest
      that among African Americans, CHRNA5-A3-B4 variants are not associated with
      baseline smoking but can influence smoking abstinence during active
      pharmacotherapy.

PMID- 24733009
TI  - Distributed dictionary learning for sparse representation in sensor networks.
AB  - This paper develops a distributed dictionary learning algorithm for sparse
      representation of the data distributed across nodes of sensor networks, where the
      sensitive or private data are stored or there is no fusion center or there exists
      a big data application. The main contributions of this paper are: 1) we decouple
      the combined dictionary atom update and nonzero coefficient revision procedure
      into two-stage operations to facilitate distributed computations, first updating
      the dictionary atom in terms of the eigenvalue decomposition of the sum of the
      residual (correlation) matrices across the nodes then implementing a local
      projection operation to obtain the related representation coefficients for each
      node; 2) we cast the aforementioned atom update problem as a set of decentralized
      optimization subproblems with consensus constraints. Then, we simplify the
      multiplier update for the symmetry undirected graphs in sensor networks and
      minimize the separable subproblems to attain the consistent estimates
      iteratively; and 3) dictionary atoms are typically constrained to be of unit norm
      in order to avoid the scaling ambiguity. We efficiently solve the resultant
      hidden convex subproblems by determining the optimal Lagrange multiplier. Some
      experiments are given to show that the proposed algorithm is an alternative
      distributed dictionary learning approach, and is suitable for the sensor network
      environment. 

PMID- 24733010
TI  - Anisotropic scattered data interpolation for pushbroom image rectification.
AB  - This paper deals with fast and accurate visualization of pushbroom image data
      from airborne and spaceborne platforms. A pushbroom sensor acquires images in a
      line-scanning fashion, and this results in scattered input data that need to be
      resampled onto a uniform grid for geometrically correct visualization. To this
      end, we model the anisotropic spatial dependence structure caused by the
      acquisition process. Several methods for scattered data interpolation are then
      adapted to handle the induced anisotropic metric and compared for the pushbroom
      image rectification problem. A trick that exploits the semiordered line structure
      of pushbroom data to improve the computational complexity several orders of
      magnitude is also presented.

PMID- 24733011
TI  - A locally adaptive system for the fusion of objective quality measures.
AB  - Objective measures to automatically predict the perceptual quality of images or
      videos can reduce the time and cost requirements of end-to-end quality
      monitoring. For reliable quality predictions, these objective quality measures
      need to respond consistently with the behavior of the human visual system (HVS).
      In practice, many important HVS mechanisms are too complex to be modeled
      directly. Instead, they can be mimicked by machine learning systems, trained on
      subjective quality assessment databases, and applied on predefined objective
      quality measures for specific content or distortion classes. On the downside,
      machine learning systems are often difficult to interpret and may even contradict
      the input objective quality measures, leading to unreliable quality predictions.
      To address this problem, we developed an interpretable machine learning system
      for objective quality assessment, namely the locally adaptive fusion (LAF). This
      paper describes the LAF system and compares its performance with traditional
      machine learning. As it turns out, the LAF system is more consistent with the
      input measures and can better handle heteroscedastic training data.

PMID- 24733012
TI  - Discriminability limits in spatio-temporal stereo block matching.
AB  - Disparity estimation is a fundamental task in stereo imaging and is a well
      studied problem. Recently, methods have been adapted to the video domain where
      motion is used as a matching criterion to help disambiguate spatially similar
      candidates. In this paper, we analyze the validity of the underlying assumptions
      of spatio-temporal disparity estimation, and determine the extent to which motion
      aids the matching process. By analyzing the error signal for spatio-temporal
      block matching under the sum of squared differences criterion and treating motion
      as a stochastic process, we determine the probability of a false match as a
      function of image features, motion distribution, image noise, and number of
      frames in the spatio-temporal patch. This performance quantification provides
      insight into when spatio-temporal matching is most beneficial in terms of the
      scene and motion, and can be used as a guide to select parameters for stereo
      matching algorithms. We validate our results through simulation and experiments
      on stereo video.

PMID- 24733013
TI  - Gradient histogram estimation and preservation for texture enhanced image
      denoising.
AB  - Natural image statistics plays an important role in image denoising, and various
      natural image priors, including gradient-based, sparse representation-based, and
      nonlocal self-similarity-based ones, have been widely studied and exploited for
      noise removal. In spite of the great success of many denoising algorithms, they
      tend to smooth the fine scale image textures when removing noise, degrading the
      image visual quality. To address this problem, in this paper, we propose a
      texture enhanced image denoising method by enforcing the gradient histogram of
      the denoised image to be close to a reference gradient histogram of the original
      image. Given the reference gradient histogram, a novel gradient histogram
      preservation (GHP) algorithm is developed to enhance the texture structures while
      removing noise. Two region-based variants of GHP are proposed for the denoising
      of images consisting of regions with different textures. An algorithm is also
      developed to effectively estimate the reference gradient histogram from the noisy
      observation of the unknown image. Our experimental results demonstrate that the
      proposed GHP algorithm can well preserve the texture appearance in the denoised
      images, making them look more natural.

PMID- 24733014
TI  - Combining LBP difference and feature correlation for texture description.
AB  - Effective characterization of texture images requires exploiting multiple visual
      cues from the image appearance. The local binary pattern (LBP) and its variants
      achieve great success in texture description. However, because the LBP(-like)
      feature is an index of discrete patterns rather than a numerical feature, it is
      difficult to combine the LBP(-like) feature with other discriminative ones by a
      compact descriptor. To overcome the problem derived from the nonnumerical
      constraint of the LBP, this paper proposes a numerical variant accordingly, named
      the LBP difference (LBPD). The LBPD characterizes the extent to which one LBP
      varies from the average local structure of an image region of interest. It is
      simple, rotation invariant, and computationally efficient. To achieve enhanced
      performance, we combine the LBPD with other discriminative cues by a covariance
      matrix. The proposed descriptor, termed the covariance and LBPD descriptor (COV
      LBPD), is able to capture the intrinsic correlation between the LBPD and other
      features in a compact manner. Experimental results show that the COV-LBPD
      achieves promising results on publicly available data sets.

PMID- 24733015
TI  - Image reconstruction from double random projection.
AB  - We present double random projection methods for reconstruction of imaging data.
      The methods draw upon recent results in the random projection literature,
      particularly on low-rank matrix approximations, and the reconstruction algorithm
      has only two simple and noniterative steps, while the reconstruction error is
      close to the error of the optimal low-rank approximation by the truncated
      singular-value decomposition. We extend the often-required symmetric
      distributions of entries in a random-projection matrix to asymmetric
      distributions, which can be more easily implementable on imaging devices.
      Experimental results are provided on the subsampling of natural images and
      hyperspectral images, and on simulated compressible matrices. Comparisons with
      other random projection methods are also provided.

PMID- 24733016
TI  - GABA and topiramate inhibit the formation of human macrophage-derived foam cells
      by modulating cholesterol-metabolism-associated molecules.
AB  - AIMS: gamma-aminobutyric acid (GABA), the principal inhibitory neurotransmitter,
      acts on GABA receptors to play an important role in the modulation of macrophage
      functions. The present study examined the effects of GABA and a GABA receptor
      agonist on modulating cholesterol-metabolism-associated molecules in human
      monocyte-derived macrophages (HMDMs). METHODS: ORO stain, HPLC, qRT-PCR, Western
      blot and EMSA were carried out using HMDMs exposed to ox-LDL with or without
      GABAergic agents as the experimental model. RESULTS: GABA and topiramate reduced
      the percentage of cholesterol ester in lipid-laden HMDMs by down-regulating SR-A,
      CD36 and LOX-1 expression and up-regulating ABCA1, ABCG1 and SR-BI expression in
      lipid-laden HMDMs. The production of TNF-alpha was decreased in GABA-and
      topiramate-treated lipid-laden HMDMs, and levels of interleukin (IL)-6 did not
      change. The activation of two signaling pathways, p38MAPK and NF-kappaB, was
      repressed by GABA and topiramate in lipid-laden HMDMs. CONCLUSION: GABA and
      topiramate inhibit the formation of human macrophage-derived foam cells and may
      be a possibility for macrophage targeted therapy of atherosclerotic lesions.

PMID- 24733017
TI  - Pathophysiology of lung injury induced by common bile duct ligation in mice.
AB  - BACKGROUND: Liver dysfunction and cirrhosis affect vasculature in several organ
      systems and cause impairment of organ functions, thereby increasing morbidity and
      mortality. Establishment of a mouse model of hepatopulmonary syndrome (HPS) would
      provide greater insights into the genetic basis of the disease. Our objectives
      were to establish a mouse model of lung injury after common bile duct ligation
      (CBDL) and to investigate pulmonary pathogenesis for application in future
      therapeutic approaches. METHODS: Eight-week-old Balb/c mice were subjected to
      CBDL. Immunohistochemical analyses and real-time quantitative reverse
      transcriptional polymerase chain reaction were performed on pulmonary tissues.
      The presence of HPS markers was detected by western blot and microarray analyses.
      RESULTS: We observed extensive proliferation of CD31-positive pulmonary vascular
      endothelial cells at 2 weeks after CBDL and identified 10 upregulated and 9 down
      regulated proteins that were associated with angiogenesis. TNF-alpha and MMP-9
      were highly expressed at 3 weeks after CBDL and were less expressed in the lungs
      of the control group. CONCLUSIONS: We constructed a mouse lung injury model by
      using CBDL. Contrary to our expectation, lung pathology in our mouse model
      exhibited differences from that of rat models, and the mechanisms responsible for
      these differences are unknown. This phenomenon may be explained by contrasting
      processes related to TNF induction of angiogenic signaling pathways in the
      inflammatory phase. Thus, we suggest that our mouse model can be applied to
      pulmonary pathological analyses in the inflammatory phase, i.e., to systemic
      inflammatory response syndrome, acute lung injury, and multiple organ dysfunction
      syndrome.

PMID- 24733018
TI  - Identification, molecular cloning and expression analysis of five RNA-dependent
      RNA polymerase genes in Salvia miltiorrhiza.
AB  - RNA-dependent RNA polymerases (RDRs) act as key components of the small RNA
      biogenesis pathways and play significant roles in post-transcriptional gene
      silencing (PTGS) and antiviral defense. However, there is no information about
      the RDR gene family in Salvia miltiorrhiza, an emerging model medicinal plant
      with great economic value. Through genome-wide predication and subsequent
      molecular cloning, five full-length S. miltiorrhiza RDR genes, termed SmRDR1
      SmRDR5, were identified. The length of SmRDR cDNAs varies between 3,262 (SmRDR5)
      and 4,130 bp (SmRDR3). The intron number of SmRDR genes varies from 3 (SmRDR1,
      SmRDR3 and SmRDR4) to 17 (SmRDR5). All of the deduced SmRDR protein sequences
      contain the conserved RdRp domain. Moreover, SmRDR2 and SmRDR4 have an additional
      RRM domain. Based on the phylogenetic tree constructed with sixteen RDRs from
      Arabidopsis, rice and S. miltiorrhiza, plant RDRs may be divided into four groups
      (RDR1-RDR4). The RDR1 group contains an AtRDR and an OsRDR, while includes two
      SmRDRs. On the contrary, the RDR3 group contains three AtRDRs and two OsRDRs, but
      has only one SmRDR. SmRDRs were differentially expressed in flowers, leaves,
      stems and roots of S. miltiorrhiza and responsive to methyl jasmonate treatment
      and cucumber mosaic virus infection. The results suggest the involvement of RDRs
      in S. miltiorrhiza development and response to abiotic and biotic stresses. It
      provides a foundation for further studying the regulation and biological
      functions of SmRDRs and the biogenesis pathways of small RNAs in S. miltiorrhiza.

PMID- 24733019
TI  - Unaltered striatal dopamine release levels in young Parkin knockout, Pink1
      knockout, DJ-1 knockout and LRRK2 R1441G transgenic mice.
AB  - Parkinson's disease (PD) is one of the most prevalent neurodegenerative brain
      diseases; it is accompanied by extensive loss of dopamine (DA) neurons of the
      substantia nigra that project to the putamen, leading to impaired motor
      functions. Several genes have been associated with hereditary forms of the
      disease and transgenic mice have been developed by a number of groups to produce
      animal models of PD and to explore the basic functions of these genes.
      Surprisingly, most of the various mouse lines generated such as Parkin KO, Pink1
      KO, DJ-1 KO and LRRK2 transgenic have been reported to lack degeneration of
      nigral DA neuron, one of the hallmarks of PD. However, modest impairments of
      motor behavior have been reported, suggesting the possibility that the models
      recapitulate at least some of the early stages of PD, including early dysfunction
      of DA axon terminals. To further evaluate this possibility, here we provide for
      the first time a systematic comparison of DA release in four different mouse
      lines, examined at a young age range, prior to potential age-dependent
      compensations. Using fast scan cyclic voltammetry in striatal sections prepared
      from young, 6-8 weeks old mice, we examined sub-second DA overflow evoked by
      single pulses and action potential trains. Unexpectedly, none of the models
      displayed any dysfunction of DA overflow or reuptake. These results, compatible
      with the lack of DA neuron loss in these models, suggest that molecular
      dysfunctions caused by the absence or mutation of these individual genes are not
      sufficient to perturb the function and survival of mouse DA neurons. 

PMID- 24733020
TI  - Population differences concerning TNF-alpha gene polymorphisms in gastric
      carcinogenesis based on meta-analysis.
AB  - BACKGROUND: Recent meta-analyses have studied population differences concerning
      interleukin (IL)-1 gene polymorphisms in gastric carcinogenesis. In addition to
      the IL-1 gene cluster, candidate genes include those encoding the pro
      inflammatory cytokine tumor necrosis factor (TNF)-alpha. The aim of the study was
      to systematically review the role of TNF-alpha-238 and TNF-alpha-308 gene
      polymorphisms (genotypes G/G, G/A, A/A) in gastric carcinogenesis by meta
      analyzing all relevant studies to look for any differences concerning TNF-alpha
      gene polymorphisms in gastric carcinogenesis. METHODS: Extensive English language
      medical literature searches for human studies were performed up to the end of May
      2013, using suitable keywords. Pooled estimates [odds ratio (OR) with 95%
      confidence intervals (CI)] were obtained using the random-effects model.
      Heterogeneity between studies was evaluated with the Cochran Q test whereas the
      likelihood of publication bias was assessed by constructing funnel plots. Their
      symmetry was estimated by the adjusted rank correlation test. RESULTS: In
      seventeen studies, from various countries, the TNF-alpha-308 and TNF-alpha-238
      frequencies of genotypes G/G, G/A, A/A were examined in gastric cancer patients
      and controls. For TNF-alpha-308 frequency overall, the pooled ORs with 95%CI for
      genotype G/G, A/A and G/A were 0.837 (0.712-0.982), 1.430 (1.064-1.923) and 1.145
      (0.973-1.348) with respective P values 0.029, 0.018 and 0.104. Subgroup analyses
      showed significant results for genotype G/G only in Asians [OR=0.774 (0.610
      0.983), P=0.036]. CONCLUSION: In this meta-analysis there was an overall
      statistically significant increased cancer risk associated with TNF-alpha-308 G/G
      and A/A genotypes. Subgroup analyses showed significant results for genotype G/G
      in Asians, whereas no such significant results were found for Caucasians and
      Hispanics.

PMID- 24733021
TI  - Outcomes in a cohort of women who discontinued maternal triple-antiretroviral
      regimens initially used to prevent mother-to-child transmission during pregnancy
      and breastfeeding--Kenya, 2003-2009.
AB  - BACKGROUND: In 2012, the World Health Organization (WHO) amended their 2010
      guidelines for women receiving limited duration, triple-antiretroviral drug
      regimens during pregnancy and breastfeeding for prevention of mother-to-child
      transmission of HIV (tARV-PMTCT) (Option B) to include the option to continue
      lifelong combination antiretroviral therapy (cART) (Option B+). We evaluated
      clinical and CD4 outcomes in women who had received antiretrovirals for
      prevention of mother-to-child transmission and then discontinued antiretrovirals
      6-months postpartum. METHODS AND FINDINGS: The Kisumu Breastfeeding Study, 2003
      2009, was a prospective, non-randomized, open-label clinical trial of tARV-PMTCT
      in ARV-naive, Kenyan women. Women received tARV-PMTCT from 34 weeks' gestation
      until 6-months postpartum when women were instructed to discontinue
      breastfeeding. Women with CD4 count (CD4) <250cells/mm3 or WHO stage III/IV prior
      to 6-months postpartum continued cART indefinitely. We estimated the change in
      CD4 after discontinuing tARV-PMTCT and the adjusted relative risk [aRR] for
      factors associated with declines in maternal CD4. We compared maternal and infant
      outcomes following weaning-when tARV-PMTCT discontinued-by maternal ARV status
      through 24-months postpartum. Compared with women who continued cART,
      discontinuing antiretrovirals was associated with infant HIV transmission and
      death (10.1% vs. 2.4%; P = 0.03). Among women who discontinued antiretrovirals,
      CD4<500 cells/mm3 at either initiation (21.8% vs. 1.5%; P = 0.002; aRR: 9.8; 95%
      confidence interval [CI]: 2.4-40.6) or discontinuation (36.9% vs. 8.3%; P<0.0001;
      aRR: 4.4; 95%-CI: 1.9-5.0) were each associated with increased risk of women
      requiring cART for their own health within 6 months after discontinuing.
      CONCLUSIONS: Considering the serious health risks to the woman's infant and the
      brief reprieve from cART gained by stopping, every country should evaluate the
      need for and feasibility to implement WHO Option B+ for PMTCT. Evaluating CD4 at
      antiretroviral initiation or 6-months postpartum can identify pregnant women who
      would most benefit from continuing cART in settings unable to implement WHO
      Option B+.

PMID- 24733022
TI  - Sequential decoding of intramuscular EMG signals via estimation of a Markov
      model.
AB  - This paper addresses the sequential decoding of intramuscular single-channel
      electromyographic (EMG) signals to extract the activity of individual motor
      neurons. A hidden Markov model is derived from the physiological generation of
      the EMG signal. The EMG signal is described as a sum of several action potentials
      (wavelet) trains, embedded in noise. For each train, the time interval between
      wavelets is modeled by a process that parameters are linked to the muscular
      activity. The parameters of this process are estimated sequentially by a Bayes
      filter, along with the firing instants. The method was tested on some simulated
      signals and an experimental one, from which the rates of detection and
      classification of action potentials were above 95% with respect to the reference
      decomposition. The method works sequentially in time, and is the first to address
      the problem of intramuscular EMG decomposition online. It has potential
      applications for man-machine interfacing based on motor neuron activities. 

PMID- 24733024
TI  - New cholinesterase inhibitory constituents from Lonicera quinquelocularis.
AB  - A phytochemical investigation on the ethyl acetate soluble fraction of Lonicera
      quinquelocularis (whole plant) led to the first time isolation of one new
      phthalate; bis(7-acetoxy-2-ethyl-5-methylheptyl) phthalate (3) and two new
      benzoates; neopentyl-4-ethoxy-3, 5-bis (3-methyl-2-butenyl benzoate (4) and
      neopentyl-4-hydroxy-3, 5-bis (3-methyl-2-butenyl benzoate (5) along with two
      known compounds bis (2-ethylhexyl phthalate (1) and dioctyl phthalate (2). Their
      structures were established on the basis of spectroscopic analysis and by
      comparison with available data in the literature. All the compounds (1-5) were
      tested for their acetylcholinesterase (AChE) and butyrylcholinesterase (BChE)
      inhibitory activities in dose dependent manner. The IC50 (50% inhibitory effect)
      values of compounds 3 and 5 against AChE were 1.65 and 3.43 uM while the values
      obtained against BChE were 5.98 and 9.84 uM respectively. Compounds 2 and 4
      showed weak inhibition profile. 

PMID- 24733025
TI  - Precise orbit determination of BeiDou constellation based on BETS and MGEX
      network.
AB  - Chinese BeiDou Navigation Satellite System is officially operational as a
      regional constellation with five Geostationary Earth Orbit (GEO) satellites, five
      Inclined Geosynchronous Satellite Orbit (IGSO) satellites and four Medium Earth
      Orbit (MEO) satellites. Observations from the BeiDou Experimental Tracking
      Stations (BETS) and the IGS Multi-GNSS Experiment (MGEX) network from 1 January
      to 31 March 2013 are processed for orbit determination of the BeiDou
      constellation. Various arc lengths and solar radiation pressure parameters are
      investigated. The reduced set of ECOM five-parameter model produces better
      performance than the full set of ECOM nine-parameter model for BeiDou IGSO and
      MEO. The orbit overlap for the middle days of 3-day arc solutions is better than
      20 cm and 14 cm for IGSO and MEO in RMS, respectively. Satellite laser ranging
      residuals are better than 10 cm for both IGSO and MEO. For BeiDou GEO, the orbit
      overlap of several meters and satellite laser ranging residuals of several
      decimetres can be achieved.

PMID- 24733026
TI  - Dual-functionalized mesoporous TiO(2) hollow nanospheres for improved CO(2)
      separation membranes.
AB  - Simultaneous improvement in CO2 permeability and CO2/N2 selectivity was obtained
      from mixed matrix membranes (MMMs) containing dual-functionalized mesoporous TiO2
      hollow nanospheres (f-MTHS). Dual functionality resulted in the increased CO2
      affinity and improved interfacial properties between inorganic nanofillers and
      the polymer matrix. 

PMID- 24733023
TI  - X chromosome regulation: diverse patterns in development, tissues and disease.
AB  - Genes on the mammalian X chromosome are present in one copy in males and two
      copies in females. The complex mechanisms that regulate the X chromosome lead to
      evolutionary and physiological variability in gene expression between species,
      the sexes, individuals, developmental stages, tissues and cell types. In early
      development, delayed and incomplete X chromosome inactivation (XCI) in some
      species causes variability in gene expression. Additional diversity stems from
      escape from XCI and from mosaicism or XCI skewing in females. This causes sex
      specific differences that manifest as differential gene expression and associated
      phenotypes. Furthermore, the complexity and diversity of X dosage regulation
      affect the severity of diseases caused by X-linked mutations. 

PMID- 24733027
TI  - Space availability in confined sheep during pregnancy, effects in movement
      patterns and use of space.
AB  - Space availability is essential to grant the welfare of animals. To determine the
      effect of space availability on movement and space use in pregnant ewes (Ovis
      aries), 54 individuals were studied during the last 11 weeks of gestation. Three
      treatments were tested (1, 2, and 3 m2/ewe; 6 ewes/group). Ewes' positions were
      collected for 15 minutes using continuous scan samplings two days/week. Total and
      net distance, net/total distance ratio, maximum and minimum step length, movement
      activity, angular dispersion, nearest, furthest and mean neighbour distance,
      peripheral location ratio, and corrected peripheral location ratio were
      calculated. Restriction in space availability resulted in smaller total travelled
      distance, net to total distance ratio, maximum step length, and angular
      dispersion but higher movement activity at 1 m2/ewe as compared to 2 and 3 m2/ewe
      (P<0.01). On the other hand, nearest and furthest neighbour distances increased
      from 1 to 3 m2/ewe (P<0.001). Largest total distance, maximum and minimum step
      length, and movement activity, as well as lowest net/total distance ratio and
      angular dispersion were observed during the first weeks (P<0.05) while inter
      individual distances increased through gestation. Results indicate that movement
      patterns and space use in ewes were clearly restricted by limitations of space
      availability to 1 m2/ewe. This reflected in shorter, more sinuous trajectories
      composed of shorter steps, lower inter-individual distances and higher movement
      activity potentially linked with higher restlessness levels. On the contrary,
      differences between 2 and 3 m2/ewe, for most variables indicate that increasing
      space availability from 2 to 3 m2/ewe would appear to have limited benefits,
      reflected mostly in a further increment in the inter-individual distances among
      group members. No major variations in spatial requirements were detected through
      gestation, except for slight increments in inter-individual distances and an
      initial adaptation period, with ewes being restless and highly motivated to
      explore their new environment. 

PMID- 24733028
TI  - A high normal ankle-brachial index is associated with proteinuria in a screened
      cohort of Japanese: the Okinawa Peripheral Arterial Disease Study.
AB  - OBJECTIVES: We hypothesized that ankle-brachial index (ABI) increased with age as
      a result of arterial stiffness, and decreased when flow-limiting atherosclerotic
      stenosis occurred in the lower limbs. As arterial stiffness is associated with
      proteinuria, we investigated the relationship between ABI and prevalence of
      proteinuria. METHODS: A cross-sectional study of ABI and proteinuria with 13,193
      participants aged 21-89 years (53% women) from health checkups between July 2003
      and March 2010 was conducted. ABI was measured using the automatic oscillometric
      method, and stratified into four groups: ABI <= 0.9 (low); 0.9 < ABI <1.0
      (borderline low); 1.0 <= ABI <1.2 (normal); and 1.2 <= ABI <1.4 (high normal).
      RESULTS: In participants with ABI at least 1.0, ABI was positively correlated
      with SBP, pulse pressure, and brachial-ankle pulse wave velocity. In participants
      with ABI less than 1.0, all indices were negatively correlated with ABI. The
      prevalence of proteinuria, defined as >= 1+ by dipstick, was significantly higher
      in low (23%) and high normal ABI (10%) compared with borderline low (6%) and
      normal ABI (7%). In participants at least 60 years, proteinuria was significantly
      associated with only low ABI [odds ratio (OR) 3.22, 95% confidence interval 1.34
      7.41] compared with normal ABI before and after multivariable adjustment. In
      participants less than 60 years, adjusted OR for proteinuria was only
      significantly associated with high normal ABI (OR 1.32, 95% confidence interval
      1.01-1.74). CONCLUSION: High normal ABI in younger participants may be a result
      of arterial stiffness and associated with proteinuria.

PMID- 24733029
TI  - Effect of changes in BMI and waist circumference on ambulatory blood pressure in
      obese children and adolescents.
AB  - BACKGROUND: Weight reduction has been accompanied with a reduction in clinic
      blood pressure (BP) in children and adolescents; however, the effect on
      ambulatory BP (ABP) is uncertain. The objective was to investigate the impact of
      weight changes on ABP in obese children and adolescents. METHODS: Sixty-one
      severely obese patients aged 10-18 years underwent lifestyle intervention at the
      Children's Obesity Clinic. Patients were examined with ABP monitoring at baseline
      and after 1 year of treatment (follow-up). To account for growth, BP and BMI were
      standardized into z scores, whereas waist circumference was indexed by height
      [waist/height ratio (WHR)]. RESULTS: Patients experienced a reduction at follow
      up in the degree of obesity [DeltaBMI z score: -0.21, 95% confidence interval
      (CI) -0.32 to -0.10, P = 0.0003; and DeltaWHR: -0.02, 95% CI -0.03 to -0.004, P =
      0.009]. Delta24-h, Deltadaytime and Deltanight-time SBP and DBP in mmHg and
      changes in equivalent z scores were related to DeltaBMI z scores and DeltaWHR.
      These relationships were reproduced in multiple regression analyses adjusted for
      relevant confounders, for example, a reduction in one BMI z score corresponds to
      a reduction in 24-h SBP by 6.5 mmHg (P < 0.05). No relationship was found between
      changes in these anthropometric obesity measures and changes in clinic BP.
      CONCLUSION: Changes in obesity measures were closely related to changes in ABP,
      but not to changes in clinic BP, in severe obese children and adolescents after 1
      year of lifestyle intervention. The findings emphasize the use of 24-h ABP
      measurements in children and adolescents.

PMID- 24733030
TI  - Coagulation factor XIIa-kinin-mediated contribution to hypertension of chronic
      kidney disease.
AB  - BACKGROUND: Activated coagulation Factor XII (FXIIa) infusion increases
      peripheral resistance (TPR) and mean arterial pressure (MAP) of Brown Norway but
      not plasma kininogen deficient Brown Norway Katholiek (BNK) rats. FXIIa
      concentrations are elevated in hypertensive end-stage renal disease patients
      receiving conventional haemodialysis (CHD). Conversion to nocturnal haemodialysis
      (NHD) lowers peripheral resistance and MAP. OBJECTIVE: To determine whether the
      plasma coagulation FXIIa-kallikrein-kinin axis contributes to the hypertension of
      chronic kidney disease (CKD). METHODS: Plasma FXIIa and haemodynamic data were
      acquired in 11 CHD patients before and after 2 months of NHD. Cardiac and
      systemic haemodynamics of Brown Norway and BNK rats rendered hypertensive and
      uremic by 5/6 nephrectomy (NX) were determined before and after acute FXIIa
      inhibition. RESULTS: FXIIa was increased three-fold in CHD patients relative to
      control plasma (P < 0.05). After conversion to NHD, both DeltaMAP and DeltaTPR
      correlated with DeltaFXIIa. In rats, plasma FXIIa was three-fold higher in both
      NX groups than respective SHAM controls (all P < 0.05), but MAP (147 +/- 4 vs.
      133 +/- 2 mmHg; P < 0.05) and TPR (2.8 +/- 0.2 vs. 2.3 +/- 0.2 units; P < 0.05)
      were greater in Brown Norway NX (n = 16) than in BNK (n = 15) NX rats. FXIIa
      correlated with MAP only in Brown Norway NX, and plasma catecholamines were
      increased relative to SHAM only in Brown Norway NX (P < 0.05). In Brown Norway NX
      rats, FXIIa inhibitor infusion decreased MAP (-12 mmHg) and TPR (-0.5 Units)
      (both P < 0.05), and halved catecholamines (P < 0.05). No such changes occurred
      in BNK NX rats. CONCLUSION: FXIIa-kininogen mediated vasoconstriction contributes
      significantly to CKD hypertension in Brown Norway rats; this novel mechanism may
      be active in humans with CKD.

PMID- 24733031
TI  - Juxta-vascular nodule segmentation based on flow entropy and geodesic distance.
AB  - Computed aided diagnosis of lung CT data is a new quantitative analysis technique
      to distinguish malignant nodules from benign ones. Nodule growth rate is a key
      indicator to discriminate between benign and malignant nodules. Accurate nodule
      segmentation is the essential for calculating the nodule growth rate. However, it
      is difficult to segment juxta-vascular nodules, due to the similar gray levels in
      nodule and attached blood vessels. To distinguish the nodule region from the
      adjacent vessel region, a flowing direction feature, referred to as the direction
      of the normal vector for a pixel, is introduced. Since blood is flowing in one
      single direction through a vessel, the normal vectors of pixels in the vessel
      region typically point in similar orientations while the directions of those in
      the nodule region can be viewed as disorganized. The entropy value of the flowing
      direction features in a neighboring region for a vessel pixel is smaller than
      that for a nodule pixel. Moreover, vessel pixels typically have a larger geodesic
      distance to the nodule center than nodule pixels. Based on k -means clustering
      method, the flow entropy, combined with the geodesic distance, is used to segment
      vessel attached nodules. The validation of the proposed segmentation algorithm
      was carried out on juxta-vascular nodules, identified in the Chinalung-CT
      screening trial and on Lung Image Database Consortium (LIDC) dataset. In fully
      automated mode, accuracies of 92.9% (26/28), 87.5%(7/8), and 94.9% (149/157) are
      reached for the outlining of juxta-vascular nodules in the Chinalung-CT, and the
      first and second datasets of LIDC, respectively. Furthermore, it is demonstrated
      that the proposed method has low time complexity and high accuracies.

PMID- 24733032
TI  - Fall detection in homes of older adults using the Microsoft Kinect.
AB  - A method for detecting falls in the homes of older adults using the Microsoft
      Kinect and a two-stage fall detection system is presented. The first stage of the
      detection system characterizes a person's vertical state in individual depth
      image frames, and then segments on ground events from the vertical state time
      series obtained by tracking the person over time. The second stage uses an
      ensemble of decision trees to compute a confidence that a fall preceded on a
      ground event. Evaluation was conducted in the actual homes of older adults, using
      a combined nine years of continuous data collected in 13 apartments. The dataset
      includes 454 falls, 445 falls performed by trained stunt actors and nine
      naturally occurring resident falls. The extensive data collection allows for
      characterization of system performance under real-world conditions to a degree
      that has not been shown in other studies. Cross validation results are included
      for standing, sitting, and lying down positions, near (within 4 m) versus far
      fall locations, and occluded versus not occluded fallers. The method is compared
      against five state-of-the-art fall detection algorithms and significantly better
      results are achieved.

PMID- 24733033
TI  - Integrative clustering by nonnegative matrix factorization can reveal coherent
      functional groups from gene profile data.
AB  - Recent developments in molecular biology and techniques for genome-wide data
      acquisition have resulted in abundance of data to profile genes and predict their
      function. These datasets may come from diverse sources and it is an open question
      how to commonly address them and fuse them into a joint prediction model. A
      prevailing technique to identify groups of related genes that exhibit similar
      profiles is profile-based clustering. Cluster inference may benefit from
      consensus across different clustering models. In this paper, we propose a
      technique that develops separate gene clusters from each of available data
      sources and then fuses them by means of nonnegative matrix factorization. We use
      gene profile data on the budding yeast S. cerevisiae to demonstrate that this
      approach can successfully integrate heterogeneous datasets and yield high-quality
      clusters that could otherwise not be inferred by simply merging the gene profiles
      prior to clustering. 

PMID- 24733034
TI  - The lag effects and vulnerabilities of temperature effects on cardiovascular
      disease mortality in a subtropical climate zone in China.
AB  - This research quantifies the lag effects and vulnerabilities of temperature
      effects on cardiovascular disease in Changsha--a subtropical climate zone of
      China. A Poisson regression model within a distributed lag nonlinear models
      framework was used to examine the lag effects of cold- and heat-related CVD
      mortality. The lag effect for heat-related CVD mortality was just 0-3 days. In
      contrast, we observed a statistically significant association with 10-25 lag days
      for cold-related CVD mortality. Low temperatures with 0-2 lag days increased the
      mortality risk for those >=65 years and females. For all ages, the cumulative
      effects of cold-related CVD mortality was 6.6% (95% CI: 5.2%-8.2%) for 30 lag
      days while that of heat-related CVD mortality was 4.9% (95% CI: 2.0%-7.9%) for 3
      lag days. We found that in Changsha city, the lag effect of hot temperatures is
      short while the lag effect of cold temperatures is long. Females and older people
      were more sensitive to extreme hot and cold temperatures than males and younger
      people.

PMID- 24733035
TI  - Nonmonotonic observer-based fuzzy controller designs for discrete time T-S fuzzy
      systems via LMI.
AB  - In this paper, based on the nonmonotonic Lyapunov functions, a new less
      conservative state feedback controller synthesis method is proposed for a class
      of discrete time nonlinear systems represented by Takagi-Sugeno (T-S) fuzzy
      systems. Parallel distributed compensation (PDC) state feedback is employed as
      the controller structure. Also, a T-S fuzzy observer is designed in a manner
      similar to state feedback controller design. The observer and the controller can
      be obtained separately and then combined together to form an output feedback
      controller by means of the Separation theorem. Both observer and controller are
      obtained via solving a sequence of linear matrix inequalities. Nonmonotonic
      Lyapunov method allows the design of controllers for the aforementioned systems
      where other methods fail. Illustrative examples are presented which show how the
      proposed method outperforms other methods such as common quadratic, piecewise or
      non quadratic Lyapunov functions. 

PMID- 24733036
TI  - On controllability of neuronal networks with constraints on the average of
      control gains.
AB  - Control gains play an important role in the control of a natural or a technical
      system since they reflect how much resource is required to optimize a certain
      control objective. This paper is concerned with the controllability of neuronal
      networks with constraints on the average value of the control gains injected in
      driver nodes, which are in accordance with engineering and biological
      backgrounds. In order to deal with the constraints on control gains, the
      controllability problem is transformed into a constrained optimization problem
      (COP). The introduction of the constraints on the control gains unavoidably leads
      to substantial difficulty in finding feasible as well as refining solutions. As
      such, a modified dynamic hybrid framework (MDyHF) is developed to solve this COP,
      based on an adaptive differential evolution and the concept of Pareto dominance.
      By comparing with statistical methods and several recently reported constrained
      optimization evolutionary algorithms (COEAs), we show that our proposed MDyHF is
      competitive and promising in studying the controllability of neuronal networks.
      Based on the MDyHF, we proceed to show the controlling regions under different
      levels of constraints. It is revealed that we should allocate the control gains
      economically when strong constraints are considered. In addition, it is found
      that as the constraints become more restrictive, the driver nodes are more likely
      to be selected from the nodes with a large degree. The results and methods
      presented in this paper will provide useful insights into developing new
      techniques to control a realistic complex network efficiently. 

PMID- 24733037
TI  - Acceleration of reinforcement learning by policy evaluation using nonstationary
      iterative method.
AB  - Typical methods for solving reinforcement learning problems iterate two steps,
      policy evaluation and policy improvement. This paper proposes algorithms for the
      policy evaluation to improve learning efficiency. The proposed algorithms are
      based on the Krylov Subspace Method (KSM), which is a nonstationary iterative
      method. The algorithms based on KSM are tens to hundreds times more efficient
      than existing algorithms based on the stationary iterative methods. Algorithms
      based on KSM are far more efficient than they have been generally expected. This
      paper clarifies what makes algorithms based on KSM makes more efficient with
      numerical examples and theoretical discussions. 

PMID- 24733038
TI  - Estimating physical activity in children: impact of pedometer wear time and
      metric.
AB  - BACKGROUND: The purpose of this study was to provide a practical demonstration of
      the impact of monitoring frame and metric when assessing pedometer-determined
      physical activity (PA) in youth. METHODS: Children (N = 1111) were asked to wear
      pedometers over a 7-day period during which time worn and steps were recorded
      each day. Varying data-exclusion criteria were used to demonstrate changes in
      estimates of PA. Steps were expressed using several metrics and criteria, and
      construct validity was demonstrated via correlations with adiposity. RESULTS:
      Meaningful fluctuations in average steps per day and percentage meeting PA
      recommendations were apparent when different criteria were used. Children who
      wore the pedometer longer appeared more active, with each minute the pedometer
      was worn each day accounting for an approximate increase of 11 and 8 steps for
      boys and girls, respectively (P < .05). Using more restrictive exclusion criteria
      led to stronger correlations between indices of steps per day, steps per minute,
      steps per leg length, steps per minute per leg length, and obesity. CONCLUSION:
      Wear time has a meaningful impact on estimates of PA. This should be considered
      when determining exclusion criteria and making comparisons between studies.
      Results also suggest that incorporating wear time per day and leg length into the
      metric may increase validity of PA estimates.

PMID- 24733039
TI  - The utility of chromosome microdissection in clinical cytogenetics: a new
      reciprocal translocation in sheep.
AB  - Local sheep breeders and scientists in Italy cooperate and conduct research on
      the genetic improvement of autochthonous genetic types (AGTs) by various
      approaches, including a cytogenetic breeding selection since 2011. The Laticauda
      sheep (Ovis aries, 2n = 54) breed is one of the AGTs reared in the Campania
      region (southern Italy). Performing cytogenetic analyses, we have detected and
      described a novel reciprocal translocation in a Laticauda sheep identified as
      54,XX t(18;23)(q14;q26). Our data support recurring appeals that suggest the
      regular performance of cytogenetic analyses for monitoring genetic health of
      livestock species. In total, 5 cases of reciprocal translocations in sheep are
      known, including the new case. None of them has any phenotypic effect on the
      living offspring. However, affected animals are characterized by sterility or
      have a low fertility which can have an effect on breeding success and on
      economical balance. Presence and kind of the described novel chromosomal
      aberration were detected by performing CBA-banding and FISH mapping with
      telomeric probes. RBA-banding allowed the karyotyping of sheep chromosomes and
      the identification of aberrant chromosomes and regions involved in the new
      reciprocal translocation. Whole chromosome painting (WCP) probes received from
      equivalent chromosomes in cattle and the derivative sheep chromosome 18 confirmed
      the cytogenetic data. This way, our study underlined both the importance of WCP
      probes by chromosome microdissection and a new way to use WCP probes directly
      generated from derivative chromosomes.

PMID- 24733040
TI  - Tanshinone IIA promotes pulmonary artery smooth muscle cell apoptosis in vitro by
      inhibiting the JAK2/STAT3 signaling pathway.
AB  - BACKGROUND: Tanshinone IIA inhibits the proliferation of pulmonary artery smooth
      muscle cells (PASMCs), but the potential mechanisms of its effects on PASMCs
      apoptosis remain unclear. METHODS: Rat were subjected to hypoxia for 9 days with
      or without Tanshinone IIA treatment. PASMCs were exposed to the conditions of 2%
      O2 and 93% N2 for 24 h in vitro. Hematoxylin and eosin (HE) staining was used to
      evaluate vascular remodeling. The Cell viability was determined using cell
      fluorescence staining and MTT assays, and apoptosis was assessed using flow
      cytometry. Protein expression was quantified by Western blotting. RESULTS: Our
      results showed that Tanshinone IIA treatment reduced pulmonary artery media
      thickening in hypoxic rats. Tanshinone IIA reduced PASMC viability in a dose
      dependent manner. Additionally, Tanshinone IIA promoted PASMC apoptosis, lowered
      Hsp60 levels, and upregulated caspase-3 expressions under hypoxic conditions.
      This pro-apoptotic effect of Tanshinone IIA might be due to the reduction of the
      phosphorylation of JAK2/STAT3 signaling markers and the increase in the levels of
      the downstream target, Cx43 in PASMCs. CONCLUSION: These data suggest that
      Tanshinone IIA promotes PASMC apoptosis during hypoxia and reverses vascular
      remodeling. This effect is mediated by modulating the expression of Hsp60,
      caspase-3, and Cx43 via the JAK2/STAT3 signaling pathway. These results might
      provide a new therapeutic target to explore a novel strategy for hypoxia-induced
      vessel remodeling.

PMID- 24733041
TI  - Radiosensitization effect of folate-conjugated gold nanoparticles on HeLa cancer
      cells under orthovoltage superficial radiotherapy techniques.
AB  - Due to the high atomic number of gold nanoparticles (GNPs), they are known as new
      radiosensitizer agents for enhancing the efficiency of superficial radiotherapy
      techniques by increasing the dose absorbed in tumor cells wherein they can be
      accumulated selectively. The aim of this study was to compare the effect of
      various common low energy levels of orthovoltage x-rays and megavoltage gamma
      rays (Co-60) on enhancing the therapeutic efficiency of HeLa cancer cells in the
      presence of conjugated folate and non-conjugated (pegylated) GNPs. To achieve
      this, GNPs with an average diameter of 52 nm were synthesized and conjugated to
      folic acid molecules. Pegylated GNPs with an average diameter of 47 nm were also
      synthesized and used as non-conjugated folate GNPs. Cytotoxicity assay of the
      synthesized folate-conjugated and pegylated GNPs was performed using different
      levels of nanoparticle concentration incubated with HeLa cells for 24 h. The
      radiosensitizing effect of both the conjugated and pegylated GNPs on the cells at
      a concentration of 50 uM was compared using MTT as well as clonogenic assays
      after exposing them to 2 Gy ionizing radiation produced by an orthovoltage x-ray
      machine at four different kVps and gamma-rays of a Co-60 unit. Significant
      differences were noted among various irradiated groups with and without the
      folate conjugation, with an average dose enhancement factor (DEF) of 1.64 +/-
      0.05 and 1.35 +/- 0.05 for the folate-conjugated and pegylated GNPs,
      respectively. The maximum DEF was obtained with the 180 kVp x-ray beam for both
      of the GNPs. Folate-conjugated GNPs can significantly enhance the cell killing
      potential of orthovoltage x-ray energies (especially at 180 kVp) in folate
      receptor-expressing cancer cells, such as HeLa, in superficial radiotherapy
      techniques. 

PMID- 24733042
TI  - Effective catalysis of imine metathesis by means of fast transiminations between
      aromatic-aromatic or aromatic-aliphatic amines.
AB  - This paper reports on a quantitative investigation of rates of amine-imine
      exchange reactions of primary amines with their benzylidene derivatives in
      organic solvents at room temperature. Exchange reactions involving aromatic
      aromatic or aromatic-aliphatic amines were in all cases fast enough to allow
      their use in the effective catalysis of imine metathesis in the absence of acid
      and metal catalysis. Transiminations based on exchange between aromatic and
      aliphatic amines were retarded both by electron-donating and electron-withdrawing
      substituents in the para-position of the benzylidene moiety. This result was
      interpreted as arising from a change in the rate-determining step of the two-step
      transimination reaction. 

PMID- 24733043
TI  - Ultrasensitive electrochemical immunoassay for avian influenza subtype H5 using
      nanocomposite.
AB  - We report a novel electrochemical immunosensor that can sensitively detect avian
      influenza virus H5 subtype (AIV H5) captured by graphene oxide-H5-polychonal
      antibodies-bovine serum albumin (GO-PAb-BSA) nanocomposite. The graphene oxide
      (GO) carried H5-polychonal antibody (PAb) were used as signal amplification
      materials. Upon signal amplification, the immunosensor showed a 256-fold increase
      in detection sensitivity compared to the immunosensor without GO-PAb-BSA. We
      designed a PAb labeling GO strategy and signal amplification procedure that allow
      ultrasensitive and selective detection of AIV H5. The established method
      responded to 2(-15) HA unit/50 uL H5, with a linear calibration range from 2(-15)
      to 2(-8) HA unit/50 uL. In summary, we demonstrated that the immunosenser has a
      high specificity and sensitivity for AIV H5, and the established assay could be
      potentially applied in the rapid detection of other pathogenic microorganisms.

PMID- 24733044
TI  - A chemical genetics analysis of the roles of bypass polymerase DinB and DNA
      repair protein AlkB in processing N2-alkylguanine lesions in vivo.
AB  - DinB, the E. coli translesion synthesis polymerase, has been shown to bypass
      several N2-alkylguanine adducts in vitro, including N2-furfurylguanine, the
      structural analog of the DNA adduct formed by the antibacterial agent
      nitrofurazone. Recently, it was demonstrated that the Fe(II)- and alpha
      ketoglutarate-dependent dioxygenase AlkB, a DNA repair enzyme, can dealkylate in
      vitro a series of N2-alkyguanines, including N2-furfurylguanine. The present
      study explored, head to head, the in vivo relative contributions of these two DNA
      maintenance pathways (replicative bypass vs. repair) as they processed a series
      of structurally varied, biologically relevant N2-alkylguanine lesions: N2
      furfurylguanine (FF), 2-tetrahydrofuran-2-yl-methylguanine (HF), 2-methylguanine,
      and 2-ethylguanine. Each lesion was chemically synthesized and incorporated site
      specifically into an M13 bacteriophage genome, which was then replicated in E.
      coli cells deficient or proficient for DinB and AlkB (4 strains in total).
      Biochemical tools were employed to analyze the relative replication efficiencies
      of the phage (a measure of the bypass efficiency of each lesion) and the base
      composition at the lesion site after replication (a measure of the mutagenesis
      profile of each lesion). The main findings were: 1) Among the lesions studied,
      the bulky FF and HF lesions proved to be strong replication blocks when
      introduced site-specifically on a single-stranded vector in DinB deficient cells.
      This toxic effect disappeared in the strains expressing physiological levels of
      DinB. 2) AlkB is known to repair N2-alkylguanine lesions in vitro; however, the
      presence of AlkB showed no relief from the replication blocks induced by FF and
      HF in vivo. 3) The mutagenic properties of the entire series of N2-alkyguanines
      adducts were investigated in vivo for the first time. None of the adducts were
      mutagenic under the conditions evaluated, regardless of the DinB or AlkB cellular
      status. Taken together, the data indicated that the cellular pathway to combat
      bulky N2-alkylguanine DNA adducts was DinB-dependent lesion bypass. 

PMID- 24733045
TI  - JNK confers 5-fluorouracil resistance in p53-deficient and mutant p53-expressing
      colon cancer cells by inducing survival autophagy.
AB  - Deficiency or mutation in the p53 tumor suppressor gene commonly occurs in human
      cancer and can contribute to disease progression and chemotherapy resistance.
      Currently, although the pro-survival or pro-death effect of autophagy remains a
      controversial issue, increasing data seem to support the idea that autophagy
      facilitates cancer cell resistance to chemotherapy treatment. Here we report that
      5-FU treatment causes aberrant autophagosome accumulation in HCT116 p53(-/-) and
      HT-29 cancer cells. Specific inhibition of autophagy by 3-MA, CQ or small
      interfering RNA treatment targeting Atg5 or Beclin 1 can potentiate the re
      sensitization of these resistant cancer cells to 5-FU. In further analysis, we
      show that JNK activation and phosphorylation of Bcl-2 are key determinants in 5
      FU-induced autophagy. Inhibition of JNK by the compound SP600125 or JNK siRNA
      suppressed autophagy and phosphorylation of c-Jun and Bcl-2 but increased 5-FU
      induced apoptosis in both HCT116 p53(-/-) and HT29 cells. Taken together, our
      results suggest that JNK activation confers 5-FU resistance in HCT116 p53(-/-)
      and HT29 cells by promoting autophagy as a pro-survival effect, likely via
      inducing Bcl-2 phosphorylation. These results provide a promising strategy to
      improve the efficacy of 5-FU-based chemotherapy for colorectal cancer patients
      harboring a p53 gene mutation. 

PMID- 24733047
TI  - An educational intervention to improve the endoscopist's ability to correctly
      diagnose small gastric lesions using magnifying endoscopy with narrow-band
      imaging.
AB  - BACKGROUND: Magnifying endoscopy with narrow-band imaging (ME-NBI) and a simple
      and systematic classification system based on microvascular and microsurface
      patterns, the "VS" classification system (VSCS), have been shown to be useful for
      the diagnosis of early gastric cancer. The aim of this study was to clarify
      whether an educational lecture about the VSCS improves performance with ME-NBI.
      METHODS: Sixty-four gastrointestinal endoscopists took the 1st exam before
      receiving the lecture about the VSCS, the 2nd exam immediately after the lecture,
      and the 3rd exam 2 months after the lecture. We compared the VSCS-based
      diagnostic accuracy among the participants before and after the lecture. RESULTS:
      The proportion of correct diagnoses was significantly higher, at 70.8% in the 2nd
      exam than in the 1st exam, at 53.1% (P<0.001). The correct diagnosis rate in the
      3rd exam was significantly lower than that in the 2nd exam (60.9% vs. 70.8%;
      P<0.001) but was still higher than that in the 1st exam (60.9% vs. 53.1%;
      P<0.001). The difference in proportion of correct diagnosis between the 2nd and
      the 3rd exams was smaller among routine ME-NBI practitioners (n=6; 79.2% and
      76.1%, respectively), compared to that among non-routine practitioners (n=34;
      71.6% and 59.8%, respectively) or non-practitioners (n=24; 67.5% and 58.8%,
      respectively). CONCLUSION: This study revealed that an educational intervention
      increased correct diagnosis rate of small gastric lesions using the VSCS,
      diagnosis criteria based on ME-NBI and also showed that the routine use of the
      modality and the diagnosis criteria was necessary to maintain diagnostic skills.

PMID- 24733046
TI  - Activity blockade and GABAA receptor blockade produce synaptic scaling through
      chloride accumulation in embryonic spinal motoneurons and interneurons.
AB  - Synaptic scaling represents a process whereby the distribution of a cell's
      synaptic strengths are altered by a multiplicative scaling factor. Scaling is
      thought to be a compensatory response that homeostatically controls spiking
      activity levels in the cell or network. Previously, we observed GABAergic
      synaptic scaling in embryonic spinal motoneurons following in vivo blockade of
      either spiking activity or GABAA receptors (GABAARs). We had determined that
      activity blockade triggered upward GABAergic scaling through chloride
      accumulation, thus increasing the driving force for these currents. To determine
      whether chloride accumulation also underlies GABAergic scaling following GABAAR
      blockade we have developed a new technique. We expressed a genetically encoded
      chloride-indicator, Clomeleon, in the embryonic chick spinal cord, which provides
      a non-invasive fast measure of intracellular chloride. Using this technique we
      now show that chloride accumulation underlies GABAergic scaling following
      blockade of either spiking activity or the GABAAR. The finding that GABAAR
      blockade and activity blockade trigger scaling via a common mechanism supports
      our hypothesis that activity blockade reduces GABAAR activation, which triggers
      synaptic scaling. In addition, Clomeleon imaging demonstrated the time course and
      widespread nature of GABAergic scaling through chloride accumulation, as it was
      also observed in spinal interneurons. This suggests that homeostatic scaling via
      chloride accumulation is a common feature in many neuronal classes within the
      embryonic spinal cord and opens the possibility that this process may occur
      throughout the nervous system at early stages of development. 

PMID- 24733048
TI  - Atrial fibrillation-linked germline GJA5/connexin40 mutants showed an increased
      hemichannel function.
AB  - Mutations in GJA5 encoding the gap junction protein connexin40 (Cx40) have been
      linked to lone atrial fibrillation. Some of these mutants result in impaired gap
      junction function due to either abnormal connexin localization or impaired gap
      junction channels, which may play a role in promoting atrial fibrillation.
      However, the effects of the atrial fibrillation-linked Cx40 mutants on
      hemichannel function have not been studied. Here we investigated two atrial
      fibrillation-linked germline Cx40 mutants, V85I and L221I. These two mutants
      formed putative gap junction plaques at cell-cell interfaces, with similar gap
      junction coupling conductance as that of wild-type Cx40. Connexin deficient HeLa
      cells expressing either one of these two mutants displayed prominent propidium
      iodide-uptake distinct from cells expressing wild-type Cx40 or other atrial
      fibrillation-linked Cx40 mutants, I75F, L229M, and Q49X. Propidium iodide-uptake
      was sensitive to [Ca2+]o and the hemichannel blockers, carbenoxolone, flufenamic
      acid and mefloquine, but was not affected by the pannexin 1 channel blocking
      agent, probenecid, indicating that uptake is most likely mediated via connexin
      hemichannels. A gain-of-hemichannel function in these two atrial fibrillation
      linked Cx40 mutants may provide a novel mechanism underlying the etiology of
      atrial fibrillation. 

PMID- 24733049
TI  - Antitumor activity of the dietary diterpene carnosol against a panel of human
      cancer cell lines.
AB  - Dietary phytochemicals found in vegetables and fruits consist of a wide variety
      of biologically active compounds with anti-carcinogenic activity. The aim of this
      study was to evaluate the antigrowth activity of carnosol, a dietary diterpene,
      as a single agent or in combination with other dietary phytochemicals or
      chemotherapeutic drugs against a panel of tumor cell lines. Carnosol decreased
      cell viability in human breast, ovarian, and intestinal tumor cell lines, and
      inhibited cancer cell adhesion on fibronectin and growth of cancer cells in
      suspension. Carnosol also inhibited EGF-induced epithelial mesenchymal transition
      in ovarian cancer cells. The combination treatment with other dietary
      phytochemicals increased the anti-proliferative activity of carnosol. The
      combination with curcumin resulted in a synergistic reduction of vitality in SKOV
      3 and MDA-231 cells and potently inhibited viability of primary cancer cells
      isolated from the pleural fluid or ascites of patients with metastatic cancers.
      These results provide additional evidence about the anticancer role of carnosol
      and its potential in blocking the growth of tumor cells. 

PMID- 24733051
TI  - Comparison of postoperative volume status and hemodynamics between surgical
      clipping and endovascular coiling in patients after subarachnoid hemorrhage.
AB  - BACKGROUND: Recent clinical data suggest that postoperative hemodynamic profile
      and fluid management may differ in aneurysmal subarachnoid hemorrhage patients
      depending on the treatment option: surgical clipping or endovascular coiling. Our
      aim was to determine the differences in hemodynamic parameters between the 2
      modalities using an advanced transpulmonary thermodilution technique. METHODS: We
      studied 73 consecutive aneurysmal subarachnoid hemorrhage patients treated with
      either clipping or coiling. Transpulmonary thermodilution was established for
      monitoring cardiac index, global end-diastolic volume index (GEDI), and
      extravascular lung water index (ELWI). Blood biochemical markers were sampled in
      parallel. RESULTS: Hypovolemia (GEDI: 656+/-72 vs. 713+/-40 mL/m; P=0.0001) and
      elevated plasma brain natriuretic peptide (114.0+/-56.7 vs. 68.6+/-47.4 pg/mL;
      P=0.0004) were evident on initial measurements in the clipping group. The number
      of fluid challenges until normalization of GEDI and ROC-based prediction of the
      responders (GEDI>=10%) during vasospasm risk period (day 4 to 14 of ictus) were
      less with coiling than with clipping (P<0.05). Therapy-related pulmonary edema
      was detected only in the clipping group (8%, n=3). Although length of intensive
      care unit stay was shorter in the coiling group (P=0.016), incidences of delayed
      ischemia (13% vs. 11%; P=0.50) and poor functional outcome on modified Rankin
      Scale score 4 to 6 at 1 month (37% vs. 46%; P=0.30) were not statistically
      different. CONCLUSIONS: Surgical clipping is associated with higher cardiac
      output and hypovolemia in the early postoperative stage and poorer preload
      responsiveness to volume therapy during the vasospasm risk period compared with
      endovascular coiling.

PMID- 24733050
TI  - Reduced virulence of an extensively drug-resistant outbreak strain of
      Mycobacterium tuberculosis in a murine model.
AB  - Bacterial drug resistance is often associated with a fitness cost. Large
      outbreaks of multidrug-resistant (MDR) and extensively drug-resistant (XDR) TB
      have been described that predominately affect persons with HIV infection. We
      obtained four closely-related Mycobacterium tuberculosis strains (genotype
      F15/LAM4/KZN) from an outbreak in KwaZulu-Natal (KZN), South Africa, including
      drug-sensitive, MDR, and XDR clinical isolates. We compared the virulence of
      these strains in a murine model of aerosol M. tuberculosis infection for four
      phenotypes: (1) competitive in vivo growth in lung and spleen, (2) non
      competitive in vivo growth in lung and spleen, (3) murine survival time, and (4)
      lung pathology. When mixtures of sensitive, MDR, and XDR KZN strains were
      aerosolized (competitive model), lung CFUs were similar at 60 days after
      infection, and spleen CFUs were ordered as follows: sensitive > MDR > XDR. When
      individual strains were aerosolized (non-competitive model), modest differences
      in lung and spleen CFUs were observed with the same ordering. C57BL/6, C3H/FeJ,
      and SCID mice all survived longer after infection with MDR as compared to
      sensitive strains. SCID mice infected with an XDR strain survived longer than
      those infected with MDR or sensitive strains. Lung pathology was reduced after
      XDR TB infection compared to sensitive or MDR TB infection. In summary,
      increasing degrees of drug resistance were associated with decreasing murine
      virulence in this collection of KZN strains as measured by all four virulence
      phenotypes. The predominance of HIV-infected patients in MDR and XDR TB outbreaks
      may be explained by decreased virulence of these strains in humans. 

PMID- 24733052
TI  - Anesthetic management of an orthopedic patient with a suspected occult spinal
      cord tumor: a review of spinal cord coning.

PMID- 24733053
TI  - Subarachnoid block in an undiagnosed isolated traumatic subarachnoid hemorrhage.

PMID- 24733054
TI  - Discovery of novel allosteric effectors based on the predicted allosteric sites
      for Escherichia coli D-3-phosphoglycerate dehydrogenase.
AB  - D-3-phosphoglycerate dehydrogenase (PGDH) from Escherichia coli catalyzes the
      first critical step in serine biosynthesis, and can be allosterically inhibited
      by serine. In a previous study, we developed a computational method for
      allosteric site prediction using a coarse-grained two-state Go Model and
      perturbation. Two potential allosteric sites were predicted for E. coli PGDH, one
      close to the active site and the nucleotide binding site (Site I) and the other
      near the regulatory domain (Site II). In the present study, we discovered
      allosteric inhibitors and activators based on site I, using a high-throughput
      virtual screen, and followed by using surface plasmon resonance (SPR) to
      eliminate false positives. Compounds 1 and 2 demonstrated a low-concentration
      activation and high-concentration inhibition phenomenon, with IC50 values of 34.8
      and 58.0 uM in enzymatic bioassays, respectively, comparable to that of the
      endogenous allosteric effector, L-serine. For its activation activity, compound 2
      exhibited an AC50 value of 34.7 nM. The novel allosteric site discovered in PGDH
      was L-serine- and substrate-independent. Enzyme kinetics studies showed that
      these compounds influenced Km, kcat, and kcat/Km. We have also performed
      structure-activity relationship studies to discover high potency allosteric
      effectors. Compound 2-2, an analog of compound 2, showed the best in vitro
      activity with an IC50 of 22.3 uM. Compounds targeting this site can be used as
      new chemical probes to study metabolic regulation in E. coli. Our study not only
      identified a novel allosteric site and effectors for PGDH, but also provided a
      general strategy for designing new regulators for metabolic enzymes. 

PMID- 24733055
TI  - Synthesis of naphthalene amino esters and arylnaphthalene lactone lignans through
      tandem reactions of 2-alkynylbenzonitriles.
AB  - Tandem reaction of 2-alkynylbenzonitriles with a Reformatsky reagent turned out
      to be a novel and efficient approach toward 1-aminonaphthalene-2-carboxylates.
      Interestingly, with 2-(3-hydroxyprop-1-ynyl)benzonitriles as the substrates, a
      more sophisticated cascade process occurred to give 9-aminonaphtho[2,3-c]furan
      1(3H)-ones in good yields. By using this tandem reaction as a key step, a concise
      and versatile synthetic strategy for the total synthesis of arylnaphthalene
      lactone lignans has been developed. 

PMID- 24733056
TI  - Unmet need, intention to use contraceptives and unwanted pregnancy in rural
      bangladesh.
AB  - CONTEXT: Unmet need for contraception has become a central concept in the family
      planning field and one of the most important indicators for program planning and
      evaluation. The measure has faced criticism, however, for not taking into account
      women's stated intention to use contraceptives. METHODS: Using longitudinal data
      on more than 2,500 rural Bangladeshi women in 128 villages, this study links
      women's contraceptive adoption and experience of unwanted pregnancy between 2006
      and 2009 to their unmet need status and their stated intention to use
      contraceptives in 2006. RESULTS: Intention to use a method was predictive of
      subsequent use for both women with and without an unmet need. Three-quarters of
      the unintended pregnancies reported between 2006 and 2009 occurred among women
      without an unmet need in 2006. In addition, nearly half of women without an unmet
      need who were pregnant or postpartum in 2006 had experienced an unwanted
      pregnancy, compared with 30% of all women classified as having an unmet need.
      CONCLUSION: To adequately meet population family planning needs, programs must
      look beyond unmet need and focus on the total demand for acceptable and effective
      methods.

PMID- 24733057
TI  - Relationship characteristics and contraceptive use among couples in urban kenya.
AB  - CONTEXT: Few studies have used couple data to identify associations between
      individual- and relationship-level characteristics and contraceptive use in urban
      areas. METHODS: Population-based survey data collected in 2010 in three Kenyan
      cities-Nairobi, Mombasa and Kisumu-were used to identify 883 couples. Bivariate
      and multivariate analyses were conducted to examine associations between
      relationship-level characteristics (i.e., desire for another child, and
      communication about desired number of children and family planning use) and
      contraceptive use among couples currently using contraceptives; additional
      analyses investigated intention to use contraceptives among couples currently not
      practicing contraception. RESULTS: Sixty percent of couples reported current use
      of contraceptives. In multivariate analyses, couples who desired another child
      were less likely to use contraceptives than couples who wanted no more children
      (odds ratio, 0.5). Couples in which both partners reported spousal communication
      about family planning in the past six months had greater odds of contraceptive
      use than couples that reported no spousal communication on the subject (3.8).
      Results from analyses examining associations between relationship-level
      characteristics and intention to use contraceptives among current nonusers
      resembled those from analyses of current contraceptive users. CONCLUSION: In this
      study, relationship-level characteristics were associated with current
      contraceptive use and intention to use contraceptives among couples in urban
      Kenya. Family planning programs that promote spousal communication about family
      planning and desired number of children may improve contraceptive use among urban
      couples.

PMID- 24733058
TI  - Injectable contraceptive sales at licensed chemical seller shops in ghana: access
      and reported use in rural and periurban communities.
AB  - CONTEXT: Most women in Ghana obtain oral contraceptives and condoms from shops
      run by licensed chemical sellers, but such shops are not legally permitted to
      sell the country's most widely used method, the injectable. Allowing shops to
      sell the injectable could increase access to and use of the method. METHODS: In
      2012-2013, semistructured telephone interviews were conducted among convenience
      samples of 94 licensed chemical seller shop operators in two districts who were
      trained to sell the injectable and of 298 women who purchased the method from
      these shops. Follow-up interviews were conducted with 92 clients approximately
      three months after their initial injectable purchase. RESULTS: Ninety-seven
      percent of shop operators reported selling the injectable, and 94% felt
      sufficiently trained to provide family planning methods and services. Virtually
      all sellers (99%) referred clients to a hospital or health facility for
      injection; none provided injections themselves. Fifty-six percent of injectable
      clients were new family planning users. Of those who completed a follow-up
      interview, 79% had purchased the injectable again from a shop. Virtually all
      clients (97%) reported getting their injection at the health facility to which
      they were referred by the seller. Women cited trust, convenience and commodities
      being in stock as key reasons for purchasing from a shop. CONCLUSION: Licensed
      chemical seller shop operators can safely sell the injectable and refer clients
      to health facilities for screening, counseling and injection.

PMID- 24733059
TI  - Differences in unintended pregnancy, contraceptive use and abortion by HIV status
      among women in Nigeria and Zambia.
AB  - CONTEXT: Sub-Saharan Africa is burdened by high rates of unintended pregnancy and
      HIV. Yet little is known about the relationship between these two health risks in
      the region. Understanding the associations between HIV status and pregnancy
      decision making may benefit strategies to reduce unintended pregnancy. METHODS:
      In 2009-2010, household-based surveys of 1,256 women in Nigeria and 1,280 women
      in Zambia collected information on social and demographic characteristics,
      unintended pregnancy, contraceptive use, abortion and self-reported HIV status.
      Multivariate models were used to examine the association of reported HIV status
      with unintended pregnancy and abortion in the five years preceding the survey and
      with contraceptive use at the time of conception. RESULTS: HIV-positive and HIV
      negative women did not differ in their odds of unintended pregnancy or of having
      an abortion. However, HIV-positive women were more likely than HIV-negative women
      to have been using a contraceptive at the time their unintended pregnancy was
      conceived (odds ratio, 3.2). Women who did not know their HIV status were less
      likely than HIV-negative women to report an unintended pregnancy (0.6). However,
      they were also less likely than HIV-negative women to have been using a
      contraceptive at the time of conception (0.5). CONCLUSION: HIV-positive women may
      be making greater efforts than HIV-negative women to prevent unintended
      pregnancy, but with less success. Efforts should be made to improve access to
      effective contraceptive methods and counseling for all women, and for HIV
      positive women in particular.

PMID- 24733060
TI  - Is age difference between partners associated with contraceptive use among
      married couples in Nigeria?
AB  - CONTEXT: The likelihood that women use contraceptives may be reduced when they
      are considerably younger than their husband, because such age differences are
      often accompanied by disparities in social position, resources and life
      experiences, which may make marital relationships inherently unequal. METHODS:
      Data from the 2008 Nigeria Demographic and Health Survey on 6,552 married couples
      in which the woman was aged 15-49 and the man was aged 15-59 were used to examine
      associations between partners' age difference and current contraceptive use.
      Associations were explored using multinomial logistic regression models that
      adjusted for women's and couples' characteristics. Separate analyses were
      conducted for couple methods (condoms, withdrawal and abstinence) and non-couple
      methods. RESULTS: Ninety-eight percent of women were younger than their partner,
      and two-fifths were younger by 10 or more years. In bivariate analyses, women who
      were less than five years younger than their partner or were 5-9 years younger
      were more likely than those who were at least 10 years younger to be using a
      couple or non-couple contraceptive method (relative risk ratios, 1.4-2.2).
      However, these associations were no longer significant after adjustment for other
      characteristics. The measures that were most consistently related to use of
      couple and non-couple methods were education level, fertility intentions and
      household wealth. CONCLUSION: Age differences between married partners are not
      associated with women's contraceptive use in Nigeria after adjustment for
      covariates. Further study is needed to understand this finding.

PMID- 24733062
TI  - Single-access laparoscopic rectal resection versus the multiport technique: a
      retrospective study with cost analysis.
AB  - BACKGROUND: Single-access laparoscopic surgery is not used routinely for the
      treatment of colorectal disease. The aim of this retrospective cohort study is to
      compare the results of single-access laparoscopic rectal resection (SALR) versus
      multiaccess laparoscopic rectal resection with a mean follow-up of 24 months.
      METHODS: This retrospective cohort study enrolled 42 patients. Between January
      2010 and June 2012, 21 SALRs were performed. These patients were compared with a
      group of 21 other patients who had undergone multiport laparoscopic rectal
      resection. This control group had the same exclusion criteria and patient
      demographics. Short-term outcomes were reassessed with a mean follow-up of 2
      years. Statistical analysis included the Student t test and Fisher's exact test.
      Finally, we performed a differential cost analysis between the 2 procedures.
      RESULTS: Exclusion criteria, patient demographics, and indication for surgery
      were similar in both groups. The conversion rate was 0% in both groups. There
      were no intraoperative complications or deaths. Bowel recovery was similar in
      both groups. No interventions, readmissions, or deaths were recorded at 30 days'
      follow-up. At a mean follow-up of 24 months, all the patients with a preoperative
      diagnosis of cancer are still alive and disease free. Considering the selected 3
      items, the mean cost per patient for single-access laparoscopic surgery and
      multiple-access laparoscopic surgery were estimated as 7213 and 7495 Euros,
      respectively. CONCLUSION: We think that SALR could be performed in selected
      patients by surgeons with high multiport laparoscopic skills. It is compulsory by
      law to evaluate outcomes and cost-effectiveness by using randomized controlled
      trials.

PMID- 24733061
TI  - Positive reinforcement mediated by midbrain dopamine neurons requires D1 and D2
      receptor activation in the nucleus accumbens.
AB  - The neural basis of positive reinforcement is often studied in the laboratory
      using intracranial self-stimulation (ICSS), a simple behavioral model in which
      subjects perform an action in order to obtain exogenous stimulation of a specific
      brain area. Recently we showed that activation of ventral tegmental area (VTA)
      dopamine neurons supports ICSS behavior, consistent with proposed roles of this
      neural population in reinforcement learning. However, VTA dopamine neurons make
      connections with diverse brain regions, and the specific efferent target(s) that
      mediate the ability of dopamine neuron activation to support ICSS have not been
      definitively demonstrated. Here, we examine in transgenic rats whether dopamine
      neuron-specific ICSS relies on the connection between the VTA and the nucleus
      accumbens (NAc), a brain region also implicated in positive reinforcement. We
      find that optogenetic activation of dopaminergic terminals innervating the NAc is
      sufficient to drive ICSS, and that ICSS driven by optical activation of dopamine
      neuron somata in the VTA is significantly attenuated by intra-NAc injections of
      D1 or D2 receptor antagonists. These data demonstrate that the NAc is a critical
      efferent target sustaining dopamine neuron-specific ICSS, identify receptor
      subtypes through which dopamine acts to promote this behavior, and ultimately
      help to refine our understanding of the neural circuitry mediating positive
      reinforcement. 

PMID- 24733063
TI  - Impact of the establishment of a specialty hernia referral center.
AB  - BACKGROUND: Creating a surgical specialty referral center requires a strong
      interest, expertise, and a market demand in that particular field, as well as
      some form of promotion. In 2004, we established a tertiary hernia referral
      center. Our goal in this study was to examine its impact on institutional volume
      and economics. MATERIALS AND METHODS: The database of all hernia repairs (2004
      2011) was reviewed comparing hernia repair type and volume and center financial
      performance. The ventral hernia repair (VHR) patient subset was further analyzed
      with particular attention paid to previous repairs, comorbidities, referral
      patterns, and the concomitant involvement of plastic surgery. RESULTS: From 2004
      to 2011, 4927 hernia repairs were performed: 39.3% inguinal, 35.5% ventral or
      incisional, 16.2% umbilical, 5.8% diaphragmatic, 1.6% femoral, and 1.5% other.
      Annual billing increased yearly from 7% to 85% and averaged 37% per year.
      Comparing 2004 with 2011, procedural volume increased 234%, and billing increased
      713%. During that period, there was a 2.5-fold increase in open VHRs, and plastic
      surgeon involvement increased almost 8-fold, (P = .004). In 2005, 51 VHR patients
      had a previous repair, 27.0% with mesh, versus 114 previous VHR in 2011, 58.3%
      with mesh (P < .0001). For VHR, in-state referrals from 2004 to 2011 increased
      340% while out-of-state referrals jumped 580%. In 2011, 21% of all patients had
      more than 4 comorbidities, significantly increased from 2004 (P = .02).
      CONCLUSION: The establishment of a tertiary, regional referral center for hernia
      repair has led to a substantial increase in surgical volume, complexity, referral
      geography, and financial benefit to the institution.

PMID- 24733064
TI  - Relationship between metabolic syndrome and moderate-to-vigorous physical
      activity in youth.
AB  - BACKGROUND: Associations of metabolic syndrome (MetS) with lifestyle behaviors in
      youth is potentially important for identifying subgroups at risk and encourage
      interventions. This study evaluates the associations among the clustering of
      metabolic risk factors and moderate-to-vigorous physical activity (MVPA) in
      youth. METHODS: The sample comprised 522 girls and 402 boys (N = 924) aged 11 to
      17 years. Height, weight, waist circumference (WC), fasting glucose, high-density
      lipoprotein cholesterol, triglycerides, and blood pressures were measured.
      Cardiorespiratory fitness (CRF) was assessed using the 20-m shuttle run test.
      MVPA was estimated with a 3-day diary. Outcome variables were statistically
      normalized and expressed as z scores. A clustered metabolic risk score was
      computed as the mean of z scores. Multiple linear regression was used to test
      associations between metabolic risk and MVPA by sex, adjusted for age, WC, and
      CRF. RESULTS: After adjustment for potential confounders, MVPA was inversely
      associated with the clustering of metabolic risk factors in girls, but not in
      boys; in addition, after adjusting for WC, the statistical model of that
      relationship was substantially improved in girls. CONCLUSION: MVPA was
      independently associated with increased risk of MetS in girls. Additional efforts
      are needed to encourage research with different analytical approach and
      standardization of criteria for MetS in youth.

PMID- 24733065
TI  - RNA sequencing analysis reveals transcriptomic variations in tobacco (Nicotiana
      tabacum) leaves affected by climate, soil, and tillage factors.
AB  - The growth and development of plants are sensitive to their surroundings.
      Although numerous studies have analyzed plant transcriptomic variation, few have
      quantified the effect of combinations of factors or identified factor-specific
      effects. In this study, we performed RNA sequencing (RNA-seq) analysis on tobacco
      leaves derived from 10 treatment combinations of three groups of ecological
      factors, i.e., climate factors (CFs), soil factors (SFs), and tillage factors
      (TFs). We detected 4980, 2916, and 1605 differentially expressed genes (DEGs)
      that were affected by CFs, SFs, and TFs, which included 2703, 768, and 507
      specific and 703 common DEGs (simultaneously regulated by CFs, SFs, and TFs),
      respectively. GO and KEGG enrichment analyses showed that genes involved in
      abiotic stress responses and secondary metabolic pathways were overrepresented in
      the common and CF-specific DEGs. In addition, we noted enrichment in CF-specific
      DEGs related to the circadian rhythm, SF-specific DEGs involved in mineral
      nutrient absorption and transport, and SF- and TF-specific DEGs associated with
      photosynthesis. Based on these results, we propose a model that explains how
      plants adapt to various ecological factors at the transcriptomic level.
      Additionally, the identified DEGs lay the foundation for future investigations of
      stress resistance, circadian rhythm and photosynthesis in tobacco. 

PMID- 24733066
TI  - Synthesis of cellulose-2,3-bis(3,5-dimethylphenylcarbamate) in an ionic liquid
      and its chiral separation efficiency as stationary phase.
AB  - A chiral selector of cellulose-2,3-bis(3,5-dimethylphenylcarbamate) (CBDMPC) was
      synthesized by reacting 3,5-dimethylphenyl isocyanate with microcrystalline
      cellulose dissolved in an ionic liquid of 1-allyl-3-methyl-imidazolium chloride
      (AMIMCl). The obtained chiral selector was effectively characterized by infrared
      spectroscopy, elemental analysis and 1H NMR. The selector was reacted with 3
      aminopropylsilanized silica gel and the CBDMPC bonded chiral stationary phase
      (CSP) was obtained. Chromatographic evaluation of the prepared CSPs was conducted
      by high performance liquid chromatographic (HPLC) and baseline separation of
      three typical fungicides including hexaconazole, metalaxyl and myclobutanil was
      achieved using n-hexane/isopropanol as the mobile phase with a flow rate 1.0
      mL/min. Experimental results also showed that AMIMCl could be recycled easily and
      reused in the preparation of CSPs as an effective reaction media. 

PMID- 24733067
TI  - Differential signaling by protease-activated receptors: implications for
      therapeutic targeting.
AB  - Protease-activated receptors (PARs) are a family of four G protein-coupled
      receptors that exhibit increasingly appreciated differences in signaling and
      regulation both within and between the receptor class. By nature of their
      proteolytic self-activation mechanism, PARs have unique processes of receptor
      activation, "ligand" binding, and desensitization/resensitization. These
      distinctive aspects have presented both challenges and opportunities in the
      targeting of PARs for therapeutic benefit-the most notable example of which is
      inhibition of PAR1 on platelets for the prevention of arterial thrombosis.
      However, more recent studies have uncovered further distinguishing features of
      PAR-mediated signaling, revealing mechanisms by which identical proteases elicit
      distinct effects in the same cell, as well as how distinct proteases produce
      different cellular consequences via the same receptor. Here we review this
      differential signaling by PARs, highlight how important distinctions between PAR1
      and PAR4 are impacting on the progress of a new class of anti-thrombotic drugs,
      and discuss how these more recent insights into PAR signaling may present further
      opportunities for manipulating PAR activation and signaling in the development of
      novel therapies. 

PMID- 24733069
TI  - Substance P activates the Wnt signal transduction pathway and enhances the
      differentiation of mouse preosteoblastic MC3T3-E1 cells.
AB  - Recent experiments have explored the impact of Wnt/beta-catenin signaling and
      Substance P (SP) on the regulation of osteogenesis. However, the molecular
      regulatory mechanisms of SP on the formation of osteoblasts is still unknown. In
      this study, we investigated the impact of SP on the differentiation of MC3T3-E1
      cells. The osteogenic effect of SP was observed at different SP concentrations
      (ranging from 10-10 to 10-8 M). To unravel the underlying mechanism, the MC3T3-E1
      cells were treated with SP after the pretreatment by neurokinin-1 (NK1)
      antagonists and Dickkopf-1 (DKK1) and gene expression levels of Wnt/beta-catenin
      signaling pathway components, as well as osteoblast differentiation markers
      (collagen type I, alkaline phosphatase, osteocalcin, and Runx2), were measured
      using quantitative polymerase chain reaction (PCR). Furthermore, protein levels
      of Wnt/beta-catenin signaling pathway were detected using Western blotting and
      the effects of SP, NK1 antagonist, and DKK1 on beta-catenin activation were
      investigated by immunofluorescence staining. Our data indicated that SP (10-9 to
      10-8 M) significantly up-regulated the expressions of osteoblastic genes. SP (10
      8 M) also elevated the mRNA level of c-myc, cyclin D1, and lymphocyte enhancer
      factor-1 (Lef1), as well as c-myc and beta-catenin protein levels, but decreased
      the expression of Tcf7 mRNA. Moreover, SP (10-8 M) promoted the transfer of beta
      catenin into nucleus. The effects of SP treatment were inhibited by the NK1
      antagonist and DKK1. These findings suggest that SP may enhance differentiation
      of MC3T3-E1 cells via regulation of the Wnt/beta-catenin signaling pathway.

PMID- 24733070
TI  - Preparation of lung-targeting, emodin-loaded polylactic acid microspheres and
      their properties.
AB  - Emodin (1,3,8-trihydroxy-6-methylanthraquinone) has been identified to have the
      potential to improve lung fibrosis and lung cancer. To avoid the liver and kidney
      toxicities and the fast metabolism of emodin, emodin-loaded polylactic acid
      microspheres (ED-PLA-MS) were prepared and their characteristics were studied. ED
      PLA-MS were prepared by the organic phase dispersion-solvent diffusion method. By
      applying an orthogonal design, our results indicated that the optimal formulation
      was 12 mg/mL PLA, 0.5% gelatin, and an organic phase:glycerol ratio of 1:20.
      Using the optimal experimental conditions, the drug loading and encapsulation
      efficiencies were (19.0+/-1.8)% and (62.2+/-2.6)%, respectively. The average
      particle size was 9.7+/-0.7 MUm. In vitro studies indicated that the ED-PLA-MS
      demonstrated a well-sustained release efficacy. The microspheres delivered
      emodin, primarily to the lungs of mice, upon intravenous injection. It was also
      detected by microscopy that partial lung inflammation was observed in lung
      tissues and no pathological changes were found in other tissues of the ED-PLA-MS
      treated animals. These results suggested that ED-PLA-MS are of potential value in
      treating lung diseases in animals.

PMID- 24733072
TI  - When is it better not to know everything?

PMID- 24733071
TI  - A rapid and efficient immunoenzymatic assay to detect receptor protein
      interactions: G protein-coupled receptors.
AB  - G protein-coupled receptors (GPCRs) represent one of the largest families of cell
      surface receptors, and are the target of at least one-third of the current
      therapeutic drugs on the market. Along their life cycle, GPCRs are accompanied by
      a range of specialized GPCR-interacting proteins (GIPs), which take part in
      receptor proper folding, targeting to the appropriate subcellular compartments
      and in receptor signaling tasks, and also in receptor regulation processes, such
      as desensitization and internalization. The direction of protein-protein
      interactions and multi-protein complexes formation is crucial in understanding
      protein function and their implication in pathological events. Although several
      methods have been already developed to assay protein complexes, some of them are
      quite laborious, expensive, and, more important, they do not generate fully
      quantitative results. Herein, we show a rapid immunoenzymatic assay to quantify
      GPCR interactionswith its signaling proteins. The recently de-orphanized GPCR,
      GPR17, was chosen as a GPCR prototype to optimize the assay. In a GPR17
      transfected cell line and primary oligodendrocyte precursor cells, GPR17
      interaction with proteins involved in the typical GPCR regulation, such as
      desensitization and internalization machinery, was investigated. The obtained
      results were validated by co-immunoprecipitation experiments, confirming this new
      method as a rapid and quantitative assay to study protein-protein interactions. 

PMID- 24733073
TI  - Spatial variability and stocks of soil organic carbon in the Gobi desert of
      Northwestern China.
AB  - Soil organic carbon (SOC) plays an important role in improving soil properties
      and the C global cycle. Limited attention, though, has been given to assessing
      the spatial patterns and stocks of SOC in desert ecosystems. In this study, we
      quantitatively evaluated the spatial variability of SOC and its influencing
      factors and estimated SOC storage in a region (40 km2) of the Gobi desert. SOC
      exhibited a log-normal depth distribution with means of 1.6, 1.5, 1.4, and 1.4 g
      kg(-1) for the 0-10, 10-20, 20-30, and 30-40 cm layers, respectively, and was
      moderately variable according to the coefficients of variation (37-42%).
      Variability of SOC increased as the sampling area expanded and could be well
      parameterized as a power function of the sampling area. Significant correlations
      were detected between SOC and soil physical properties, i.e. stone, sand, silt,
      and clay contents and soil bulk density. The relatively coarse fractions, i.e.
      sand, silt, and stone contents, had the largest effects on SOC variability.
      Experimental semivariograms of SOC were best fitted by exponential models. Nugget
      to-sill ratios indicated a strong spatial dependence for SOC concentrations at
      all depths in the study area. The surface layer (0-10 cm) had the largest spatial
      dependency compared with the other layers. The mapping revealed a decreasing
      trend of SOC concentrations from south to north across this region of the Gobi
      desert, with higher levels close to an oasis and lower levels surrounded by
      mountains and near the desert. SOC density to depths of 20 and 40 cm for this 40
      km2 area was estimated at 0.42 and 0.68 kg C m(-2), respectively. This study
      provides an important contribution to understanding the role of the Gobi desert
      in the global carbon cycle.

PMID- 24733068
TI  - Obesity and its metabolic complications: the role of adipokines and the
      relationship between obesity, inflammation, insulin resistance, dyslipidemia and
      nonalcoholic fatty liver disease.
AB  - Accumulating evidence indicates that obesity is closely associated with an
      increased risk of metabolic diseases such as insulin resistance, type 2 diabetes,
      dyslipidemia and nonalcoholic fatty liver disease. Obesity results from an
      imbalance between food intake and energy expenditure, which leads to an excessive
      accumulation of adipose tissue. Adipose tissue is now recognized not only as a
      main site of storage of excess energy derived from food intake but also as an
      endocrine organ. The expansion of adipose tissue produces a number of bioactive
      substances, known as adipocytokines or adipokines, which trigger chronic low
      grade inflammation and interact with a range of processes in many different
      organs. Although the precise mechanisms are still unclear, dysregulated
      production or secretion of these adipokines caused by excess adipose tissue and
      adipose tissue dysfunction can contribute to the development of obesity-related
      metabolic diseases. In this review, we focus on the role of several adipokines
      associated with obesity and the potential impact on obesity-related metabolic
      diseases. Multiple lines evidence provides valuable insights into the roles of
      adipokines in the development of obesity and its metabolic complications. Further
      research is still required to fully understand the mechanisms underlying the
      metabolic actions of a few newly identified adipokines. 

PMID- 24733078
TI  - Obesity. Beneficial effects of bariatric surgery are mediated by FXR signalling.

PMID- 24733074
TI  - Analysis of the robustness of network-based disease-gene prioritization methods
      reveals redundancy in the human interactome and functional diversity of disease
      genes.
AB  - Complex biological systems usually pose a trade-off between robustness and
      fragility where a small number of perturbations can substantially disrupt the
      system. Although biological systems are robust against changes in many external
      and internal conditions, even a single mutation can perturb the system
      substantially, giving rise to a pathophenotype. Recent advances in identifying
      and analyzing the sequential variations beneath human disorders help to
      comprehend a systemic view of the mechanisms underlying various disease
      phenotypes. Network-based disease-gene prioritization methods rank the relevance
      of genes in a disease under the hypothesis that genes whose proteins interact
      with each other tend to exhibit similar phenotypes. In this study, we have tested
      the robustness of several network-based disease-gene prioritization methods with
      respect to the perturbations of the system using various disease phenotypes from
      the Online Mendelian Inheritance in Man database. These perturbations have been
      introduced either in the protein-protein interaction network or in the set of
      known disease-gene associations. As the network-based disease-gene prioritization
      methods are based on the connectivity between known disease-gene associations, we
      have further used these methods to categorize the pathophenotypes with respect to
      the recoverability of hidden disease-genes. Our results have suggested that, in
      general, disease-genes are connected through multiple paths in the human
      interactome. Moreover, even when these paths are disturbed, network-based
      prioritization can reveal hidden disease-gene associations in some
      pathophenotypes such as breast cancer, cardiomyopathy, diabetes, leukemia,
      parkinson disease and obesity to a greater extend compared to the rest of the
      pathophenotypes tested in this study. Gene Ontology (GO) analysis highlighted the
      role of functional diversity for such diseases. 

PMID- 24733079
TI  - Colorectal cancer. Understanding the routes of metastasis in colorectal cancer.

PMID- 24733080
TI  - Liver transplantation: macrosteatosis and microsteatosis respond differently to
      intermittent hepatic inflow occlusion.

PMID- 24733082
TI  - Colonic involvement in amebic liver abscess: does site matter?
AB  - BACKGROUND: Colonic involvement in amebic liver abscess (ALA) occurs in more than
      half of the patients. However no studies have found any association between the
      site of the colonic lesions and location of abscesses in the liver. Thus, the
      present study was designed to find the correlation between colonic involvement in
      solitary and multiple ALAs. METHODS: This is a case control study of 80 patients
      allocated in two groups, the first with solitary (controls) and the second with
      multiple ALAs (cases). Colonoscopy was performed in all patients enrolled in the
      study. RESULTS: Solitary ALA was seen in 70% of patients whereas multiple ALAs in
      30%. Colonic involvement in the form of erythema, inflammation and ulceration was
      seen in 77.5% of cases of ALA. 71.4 % cases of solitary ALA had colonic lesions
      compared to 91.6% cases of multiple ALAs (P=0.02). Most of the patients with
      multiple ALAs had involvement of the transverse and right colon (75%).
      Involvement of right colon was present in all patients with colonic involvement.
      A significant involvement of the right and transverse colon was seen in cases of
      multiple compared to solitary ALA (P<0.0001). CONCLUSION: Colonic involvement is
      present in more than two thirds of patients with ALA. When colonic involvement is
      present, right colon lesion is universally present. Colonic involvement may
      extend beyond hepatic flexure in patients with multiple amebic ALAs, either
      involving right hepatic lobe or both lobes.

PMID- 24733083
TI  - Synthetic routes to the Neuropeptide Y Y1 receptor antagonist 1229U91 and related
      analogues for SAR studies and cell-based imaging.
AB  - The potent Y1 receptor antagonist, 1229U91 has an unusual cyclic dimer structure
      that makes syntheses of analogue series quite challenging. We have examined three
      new routes to the synthesis of such peptides that has given access to novel
      structural variants including heterodimeric compounds, ring size variants and
      labelled conjugates. These compounds, including a fluorescently labelled analogue
      VIII show potent antagonism that can be utilised in studying Y1 receptor
      pharmacology. 

PMID- 24733084
TI  - Bipolar disorder in primary care: clinical characteristics of 740 primary care
      patients with bipolar disorder.
AB  - OBJECTIVE: This study aimed to describe the characteristics of primary care
      patients with bipolar disorder enrolled in a statewide mental health integration
      program (MHIP). METHODS: With the Composite International Diagnostic Interview
      (Version 3.0) and clinician diagnosis, 740 primary care patients with bipolar
      disorder were identified in Washington State between January 2008 and December
      2011. Clinical rating scales were administered to patients at the time of
      enrollment and during treatment. Quality-of-care outcomes were obtained from a
      systematic review of the patient disease registry and compared with a previous
      study of patients with depressive symptoms in an MHIP. Descriptive analysis
      techniques were used to describe patients' clinical characteristics. RESULTS:
      Primary care patients with bipolar disorder had high symptom severity on
      depression and anxiety measures: Patient Health Questionaire-9 (mean+/-SD score
      of 18.1+/-5.9 out of 27) and the seven-item Generalized Anxiety Disorder scale
      (15.7+/-4.7 out of 21). Psychosocial problems were common, with approximately 53%
      reporting concerns about housing, 15% reporting homelessness, and 22% reporting
      lack of a support person. Only 26% of patients were referred to specialty mental
      health treatment. Patients with bipolar disorder had a greater amount of contact
      with clinicians during treatment compared with patients with depressive symptoms
      from a prior study. CONCLUSIONS: Primary care patients with bipolar disorder
      enrolled in MHIP had severe depression, symptoms of comorbid psychiatric
      illnesses, and multiple psychosocial problems. Patients with bipolar disorder
      received more intensive care compared with patients with depressive symptoms from
      a prior study. Referral to a community mental health center occurred infrequently
      even though most patients had persistent symptoms.

PMID- 24733086
TI  - Faraday rotation echo spectroscopy and detection of quantum fluctuations.
AB  - Central spin decoherence is useful for detecting many-body physics in
      environments and moreover, the spin echo control can remove the effects of static
      thermal fluctuations so that the quantum fluctuations are revealed. The central
      spin decoherence approach, however, is feasible only in some special
      configurations and often requires uniform coupling between the central spin and
      individual spins in the baths, which are very challenging in experiments. Here,
      by making analogue between central spin decoherence and depolarization of
      photons, we propose a scheme of Faraday rotation echo spectroscopy (FRES) for
      studying quantum fluctuations in interacting spin systems. The echo control of
      the photon polarization is realized by flipping the polarization with a
      birefringence crystal. The FRES, similar to spin echo in magnetic resonance
      spectroscopy, can suppress the effects of the static magnetic fluctuations and
      therefore reveal dynamical magnetic fluctuations. We apply the scheme to a rare
      earth compound LiHoF4 and calculate the echo signal, which is related to the
      quantum fluctuations of the system. We observe enhanced signals at the phase
      boundary. The FRES should be useful for studying quantum fluctuations in a broad
      range of spin systems, including cold atoms, quantum dots, solid-state
      impurities, and transparent magnetic materials. 

PMID- 24733085
TI  - Assembly of the cardiac intercalated disk during pre- and postnatal development
      of the human heart.
AB  - BACKGROUND: In cardiac muscle, the intercalated disk (ID) at the longitudinal
      cell-edges of cardiomyocytes provides as a macromolecular infrastructure that
      integrates mechanical and electrical coupling within the heart.
      Pathophysiological disturbance in composition of this complex is well known to
      trigger cardiac arrhythmias and pump failure. The mechanisms underlying assembly
      of this important cellular domain in human heart is currently unknown. METHODS:
      We collected 18 specimens from individuals that died from non-cardiovascular
      causes. Age of the specimens ranged from a gestational age of 15 weeks through 11
      years postnatal. Immunohistochemical labeling was performed against proteins
      comprising desmosomes, adherens junctions, the cardiac sodium channel and gap
      junctions to visualize spatiotemporal alterations in subcellular location of the
      proteins. RESULTS: Changes in spatiotemporal localization of the adherens
      junction proteins (N-cadherin and ZO-1) and desmosomal proteins (plakoglobin,
      desmoplakin and plakophilin-2) were identical in all subsequent ages studied.
      After an initial period of diffuse and lateral labelling, all proteins were fully
      localized in the ID at approximately 1 year after birth. Nav1.5 that composes the
      cardiac sodium channel and the gap junction protein Cx43 follow a similar pattern
      but their arrival in the ID is detected at (much) later stages (two years for
      Nav1.5 and seven years for Cx43, respectively). CONCLUSION: Our data on
      developmental maturation of the ID in human heart indicate that generation of the
      mechanical junctions at the ID precedes that of the electrical junctions with a
      significant difference in time. In addition arrival of the electrical junctions
      (Nav1.5 and Cx43) is not uniform since sodium channels localize much earlier than
      gap junction channels.

PMID- 24733087
TI  - Serum NGF, BDNF and IL-6 levels in postpartum mothers as predictors of infant
      development: the influence of affective disorders.
AB  - BACKGROUND: Early adverse experiences are associated with increased risk of
      developing psychiatric disorders, although little is known about the
      neurobiological mediators involved. The mechanisms by which early environmental
      influences may mediate vulnerability in the development of offspring await
      further investigation. The present study correlated the NGF, BDNF, IL-6 and
      cortisol levels of mothers with postpartum affective disorders (PPAD) with infant
      development. METHODS: A longitudinal study was performed with 152 pregnant women
      and their infants. Between 60 and 120 days after delivery, women were interviewed
      and provided biological samples for biochemical analysis, and the infants were
      examined for neurobiological-motor development. RESULTS: Overall, the mothers'
      history of affective disorders, PPAD and anxiety disorder were associated with
      infant motor development. Using an adjusted linear regression analysis, PPAD (p =
      0.049), maternal anxiety disorder (p = 0.043), NGF level (p = 0.034) and infant
      cortisol level (p = 0.013) were associated with infant motor development. Using a
      factorial analysis of primary components, two components were retained. The
      psychological factor was characterized by a positive loading of a history of
      affective disorder, PPAD and anxiety disorder. For the biological factor, infant
      cortisol adhered negatively with infant motor development, but NGF was positively
      associated. The psychological factor had a negative association, but the
      biological factor had a positive association with infant motor development.
      CONCLUSIONS: There are few studies that have focused on the relationship of
      biomarkers and infant neurodevelopment. Our study points that psychological and
      biological factors are associated with infant motor development, however the
      causal relationship between these factors is still to be defined.

PMID- 24733088
TI  - Microfluidic generation of chitosan/CpG oligodeoxynucleotide nanoparticles with
      enhanced cellular uptake and immunostimulatory properties.
AB  - Chitosan/cytosine-phosphodiester-guanine oligodeoxynucleotide (CpG ODN)
      nanoparticles as potential immunostimulatory adjuvants were synthesized by the
      conventional bulk mixing (BM) method and a novel microfluidic (MF) method. Their
      size and size distribution, CpG ODN loading efficiency, surface charge,
      biocompatibility, cellular uptake, and immunostimulatory response were
      investigated. In the BM method, nanoparticles were synthesized by vortexing a
      mixture of chitosan solution and CpG ODN2006x3-PD solution. In the MF method, the
      nanoparticles were synthesized by rapidly mixing a chitosan solution and CpG ODN
      solution in a poly(dimethylsiloxane) microfluidic device. Our results indicated
      that particle size and size distribution, CpG ODN loading efficiency, and surface
      charge could be easily adjusted by using the tuning preparation method and
      controlling the flow ratio of fluid rates in the different microfluidic channels.
      Compared with the BM method, the MF method yielded a decrease in particle size
      and size range, an increase in CpG ODN loading efficiency, and a decrease in
      surface charge. After the particles were exposed to 293XL-hTLR9 cells, a water
      soluble tetrazolium salt assay indicated that the BM and MF-processed
      nanoparticles had no significant toxicity and were biocompatible. An
      immunochemical assay indicated that both types of nanoparticles entered 293XL
      hTLR9 cells and were located in the endolysosomes. The MF-processed nanoparticles
      showed much higher cellular uptake efficiency. After the particles were exposed
      to peripheral blood mononuclear cells, an enzyme-linked immunosorbent assay
      quantitatively indicated that both types of nanoparticles stimulated the
      production of interleukin-6 and the MF-processed nanoparticles showed a much
      stronger immunostimulatory response. These results indicate that the MF method
      can be used to synthesize nanoparticles with a controllable size and size range
      for enhancing the biological activity of DNA and other biomolecules. 

PMID- 24733089
TI  - Gene expression profiling identifies microphthalmia-associated transcription
      factor (MITF) and Dickkopf-1 (DKK1) as regulators of microenvironment-driven
      alterations in melanoma phenotype.
AB  - BACKGROUND: The diversity of functional phenotypes observed within a tumor does
      not exclusively result from intratumoral genetic heterogeneity but also from the
      response of cancer cells to the microenvironment. We have previously demonstrated
      that the morphological and functional phenotypes of melanoma can be dynamically
      altered upon external stimuli. FINDINGS: In the present study, transcriptome
      profiles were generated to explore the molecules governing phenotypes of
      melanospheres grown in the bFGF(+)EGF(+) serum-free cultures and monolayers
      maintained in the serum-containing medium. Higher expression levels of MITF
      dependent genes that are responsible for differentiation, e.g., TYR and MLANA,
      and stemness-related genes, e.g., ALDH1A1, were detected in melanospheres. These
      results were supported by the observation that the melanospheres contained more
      pigmented cells and cells exerting the self-renewal capacity than the monolayers.
      In addition, the expression of the anti-apoptotic, MITF-dependent genes e.g.,
      BCL2A1 was also higher in the melanospheres. The enhanced activity of MITF in
      melanospheres, as illustrated by the increased expression of 74 MITF-dependent
      genes, identified MITF as a central transcriptional regulator in melanospheres.
      Importantly, several genes including MITF-dependent ones were expressed in
      melanospheres and original tumors at similar levels. The reduced MITF level in
      monolayers might be partially explained by suppression of the Wnt/beta-catenin
      pathway, and DKK1, a secreted inhibitor of this pathway, was highly up-regulated
      in monolayers in comparison to melanospheres and original tumors. Furthermore,
      the silencing of DKK1 in monolayers increased the percentage of cells with self
      renewing capacity. CONCLUSIONS: Our study indicates that melanospheres can be
      used to unravel the molecular pathways that sustain intratumoral phenotypic
      heterogeneity. Melanospheres directly derived from tumor specimens more
      accurately mirrored the morphology and gene expression profiles of the original
      tumors compared to monolayers. Therefore, melanospheres represent a relevant
      preclinical tool to study new anticancer treatment strategies.

PMID- 24733090
TI  - Site-dependent recruitment of inflammatory cells determines the effective dose of
      Leishmania major.
AB  - The route of pathogen inoculation by needle has been shown to influence the
      outcome of infection. Employing needle inoculation of the obligately
      intracellular parasite Leishmania major, which is transmitted in nature following
      intradermal (i.d.) deposition of parasites by the bite of an infected sand fly,
      we identified differences in the preexisting and acute cellular responses in mice
      following i.d. inoculation of the ear, subcutaneous (s.c.) inoculation of the
      footpad, or inoculation of the peritoneal cavity (intraperitoneal [i.p.]
      inoculation). Initiation of infection at different sites was associated with
      different phagocytic populations. Neutrophils were the dominant infected cells
      following i.d., but not s.c. or i.p., inoculation. Inoculation of the ear dermis
      resulted in higher frequencies of total and infected neutrophils than inoculation
      of the footpad, and these higher frequencies were associated with a 10-fold
      increase in early parasite loads. Following inoculation of the ear in the absence
      of neutrophils, parasite phagocytosis by other cell types did not increase, and
      fewer parasites were able to establish infection. The frequency of infected
      neutrophils within the total infected CD11b(+) population was higher than the
      frequency of total neutrophils within the total CD11b(+) population,
      demonstrating that neutrophils are overrepresented as a proportion of infected
      cells. Employing i.d. inoculation to model sand fly transmission of parasites has
      significant consequences for infection outcome relative to that of s.c. or i.p.
      inoculation, including the phenotype of infected cells and the number of
      parasites that establish infection. Vector-borne infections initiated in the
      dermis likely involve adaptations to this unique microenvironment. Bypassing or
      altering this initial step has significant consequences for infection. 

PMID- 24733091
TI  - A Listeria monocytogenes-based vaccine that secretes sand fly salivary protein
      LJM11 confers long-term protection against vector-transmitted Leishmania major.
AB  - Cutaneous leishmaniasis is a sand fly-transmitted disease characterized by skin
      ulcers that carry significant scarring and social stigmatization. Over the past
      years, there has been cumulative evidence that immunity to specific sand fly
      salivary proteins confers a significant level of protection against
      leishmaniasis. In this study, we used an attenuated strain of Listeria
      monocytogenes as a vaccine expression system for LJM11, a sand fly salivary
      protein identified as a good vaccine candidate. We observed that mice were best
      protected against an intradermal needle challenge with Leishmania major and sand
      fly saliva when vaccinated intravenously. However, this protection was short
      lived. Importantly, groups of vaccinated mice were protected long term when
      challenged with infected sand flies. Protection correlated with smaller lesion
      size, fewer scars, and better parasite control between 2 and 6 weeks
      postchallenge compared to the control group of mice vaccinated with the parent L.
      monocytogenes strain not expressing LJM11. Moreover, protection correlated with
      high numbers of CD4(+), gamma interferon-positive (IFN-gamma(+)), tumor necrosis
      factor alpha-positive/negative (TNF-alpha(+/-)), interleukin-10-negative (IL-10(
      )) cells and low numbers of CD4(+) IFN-gamma(+/-) TNF-alpha(-) IL-10(+) T cells
      at 2 weeks postchallenge. Overall, our data indicate that delivery of LJM11 by
      Listeria is a promising vaccination strategy against cutaneous leishmaniasis
      inducing long-term protection against ulcer formation following a natural
      challenge with infected sand flies. 

PMID- 24733092
TI  - Role of intracellular carbon metabolism pathways in Shigella flexneri virulence.
AB  - Shigella flexneri, which replicates in the cytoplasm of intestinal epithelial
      cells, can use the Embden-Meyerhof-Parnas, Entner-Doudoroff, or pentose phosphate
      pathway for glycolytic carbon metabolism. To determine which of these pathways is
      used by intracellular S. flexneri, mutants were constructed and tested in a
      plaque assay for the ability to invade, replicate intracellularly, and spread to
      adjacent epithelial cells. Mutants blocked in the Embden-Meyerhof-Parnas pathway
      (pfkAB and pykAF mutants) invaded the cells but formed very small plaques. Loss
      of the Entner-Doudoroff pathway gene eda resulted in small plaques, but the
      double eda edd mutant formed normal-size plaques. This suggested that the plaque
      defect of the eda mutant was due to buildup of the toxic intermediate 2-keto-3
      deoxy-6-phosphogluconic acid rather than a specific requirement for this pathway.
      Loss of the pentose phosphate pathway had no effect on plaque formation,
      indicating that it is not critical for intracellular S. flexneri. Supplementation
      of the epithelial cell culture medium with pyruvate allowed the glycolysis
      mutants to form larger plaques than those observed with unsupplemented medium,
      consistent with data from phenotypic microarrays (Biolog) indicating that
      pyruvate metabolism was not disrupted in these mutants. Interestingly, the wild
      type S. flexneri also formed larger plaques in the presence of supplemental
      pyruvate or glucose, with pyruvate yielding the largest plaques. Analysis of the
      metabolites in the cultured cells showed increased intracellular levels of the
      added compound. Pyruvate increased the growth rate of S. flexneri in vitro,
      suggesting that it may be a preferred carbon source inside host cells. 

PMID- 24733093
TI  - Chlamydia trachomatis polymorphic membrane protein D is a virulence factor
      involved in early host-cell interactions.
AB  - Chlamydia trachomatis is an obligate intracellular mucosotropic pathogen of
      significant medical importance. It is the etiological agent of blinding trachoma
      and bacterial sexually transmitted diseases, infections that afflict hundreds of
      millions of people globally. The C. trachomatis polymorphic membrane protein D
      (PmpD) is a highly conserved autotransporter and the target of broadly cross
      reactive neutralizing antibodies; however, its role in host-pathogen interactions
      is unknown. Here we employed a targeted reverse genetics approach to generate a
      pmpD null mutant that was used to define the role of PmpD in the pathogenesis of
      chlamydial infection. We show that pmpD is not an essential chlamydial gene and
      the pmpD null mutant has no detectable deficiency in cultured murine cells or in
      a murine mucosal infection model. Notably, however, the pmpD null mutant was
      significantly attenuated for macaque eyes and cultured human cells. A reduction
      in pmpD null infection of human endocervical cells was associated with a
      deficiency in chlamydial attachment to cells. Collectively, our results show that
      PmpD is a chlamydial virulence factor that functions in early host-cell
      interactions. This study is the first of its kind using reverse genetics to
      evaluate the contribution of a C. trachomatis gene to disease pathogenesis. 

PMID- 24733094
TI  - Identification of a diguanylate cyclase and its role in Porphyromonas gingivalis
      virulence.
AB  - Porphyromonas gingivalis is a Gram-negative obligate anaerobic bacterium and is
      considered a keystone pathogen in the initiation of periodontitis, one of the
      most widespread infectious diseases. Bacterial bis-(3'-5') cyclic GMP (cyclic di
      GMP [c-di-GMP]) serves as a second messenger and is involved in modulating
      virulence factors in numerous bacteria. However, the role of this second
      messenger has not been investigated in P. gingivalis, mainly due to a lack of an
      annotation regarding diguanylate cyclases (DGCs) in this bacterium. Using
      bioinformatics tools, we found a protein, PGN_1932, containing a GGDEF domain. A
      deletion mutation in the pgn_1932 gene had a significant effect on the
      intracellular c-di-GMP level in P. gingivalis. Genetic analysis showed that
      expression of the fimA and rgpA genes, encoding the major protein subunit of
      fimbriae and an arginine-specific proteinase, respectively, was downregulated in
      the pgn_1932 mutant. Correspondingly, FimA protein production and the fimbrial
      display on the mutant were significantly reduced. Mutations in the pgn_1932 gene
      also had a significant impact on the adhesive and invasive capabilities of P.
      gingivalis, which are required for its pathogenicity. These findings provide
      evidence that the PGN_1932 protein is both responsible for synthesizing c-di-GMP
      and involved in biofilm formation and host cell invasion by P. gingivalis by
      controlling the expression and biosynthesis of FimA. 

PMID- 24733095
TI  - Antiapoptotic activity of Coxiella burnetii effector protein AnkG is controlled
      by p32-dependent trafficking.
AB  - Intracellular bacterial pathogens frequently inhibit host cell apoptosis to
      ensure survival of their host, thereby allowing bacterial propagation. The
      obligate intracellular pathogen Coxiella burnetii displays antiapoptotic activity
      which depends on a functional type IV secretion system (T4SS). Accordingly,
      antiapoptotic T4SS effector proteins, like AnkG, have been identified. AnkG
      inhibits pathogen-induced apoptosis, possibly by binding to the host cell
      mitochondrial protein p32 (gC1qR). However, the molecular mechanism of AnkG
      activity remains unknown. Here, we demonstrate that ectopically expressed AnkG
      associates with mitochondria and traffics into the nucleus after apoptosis
      induction, although AnkG lacks a predicted nuclear localization signal. We
      identified the p32 interaction region in AnkG and constructed an AnkG mutant
      (AnkGR(22/23S)) unable to bind to p32. By using this mutant, we found that
      intracellular localization and trafficking of AnkG into the nucleus are dependent
      on binding to p32. Furthermore, we demonstrated that nuclear localization of AnkG
      but not binding to p32 is required for apoptosis inhibition. Thus, the
      antiapoptotic activity of AnkG is controlled by p32-mediated intracellular
      trafficking, which, in turn, seems to be regulated by host cell processes that
      sense stress.

PMID- 24733096
TI  - Giardia duodenalis cathepsin B proteases degrade intestinal epithelial
      interleukin-8 and attenuate interleukin-8-induced neutrophil chemotaxis.
AB  - Giardia duodenalis (syn. G. intestinalis, G. lamblia) infections are a leading
      cause of waterborne diarrheal disease that can also result in the development of
      postinfectious functional gastrointestinal disorders via mechanisms that remain
      unclear. Parasite numbers exceed 10(6) trophozoites per centimeter of gut at the
      height of an infection. Yet the intestinal mucosa of G. duodenalis-infected
      individuals is devoid of signs of overt inflammation. G. duodenalis infections
      can also occur concurrently with infections with other proinflammatory
      gastrointestinal pathogens. Little is known of whether and how this parasite can
      attenuate host inflammatory responses induced by other proinflammatory stimuli,
      such as a gastrointestinal pathogen. Identifying hitherto-unrecognized parasitic
      immunomodulatory pathways, the present studies demonstrated that G. duodenalis
      trophozoites attenuate secretion of the potent neutrophil chemoattractant
      interleukin-8 (CXCL8); these effects were observed in human small intestinal
      mucosal tissues and from intestinal epithelial monolayers, activated through
      administration of proinflammatory interleukin-1beta or Salmonella enterica
      serovar Typhimurium. This attenuation is caused by the secretion of G. duodenalis
      cathepsin B cysteine proteases that degrade CXCL8 posttranscriptionally.
      Furthermore, the degradation of CXCL8 via G. duodenalis cathepsin B cysteine
      proteases attenuates CXCL8-induced chemotaxis of human neutrophils. Taken
      together, these data demonstrate for the first time that G. duodenalis
      trophozoite cathepsins are capable of attenuating a component of their host's
      proinflammatory response induced by a separate proinflammatory stimulus. 

PMID- 24733097
TI  - The type II secretion pathway in Vibrio cholerae is characterized by growth phase
      dependent expression of exoprotein genes and is positively regulated by sigmaE.
AB  - Vibrio cholerae, an etiological agent of cholera, circulates between aquatic
      reservoirs and the human gastrointestinal tract. The type II secretion (T2S)
      system plays a pivotal role in both stages of the lifestyle by exporting multiple
      proteins, including cholera toxin. Here, we studied the kinetics of expression of
      genes encoding the T2S system and its cargo proteins. We have found that under
      laboratory growth conditions, the T2S complex was continuously expressed
      throughout V. cholerae growth, whereas there was growth phase-dependent
      transcriptional activity of genes encoding different cargo proteins. Moreover,
      exposure of V. cholerae to different environmental cues encountered by the
      bacterium in its life cycle induced transcriptional expression of T2S. Subsequent
      screening of a V. cholerae genomic library suggested that sigma(E) stress
      response, phosphate metabolism, and the second messenger 3',5'-cyclic diguanylic
      acid (c-di-GMP) are involved in regulating transcriptional expression of T2S.
      Focusing on sigma(E), we discovered that the upstream region of the T2S operon
      possesses both the consensus sigma(E) and sigma(70) signatures, and deletion of
      the sigma(E) binding sequence prevented transcriptional activation of T2S by
      RpoE. Ectopic overexpression of sigma(E) stimulated transcription of T2S in wild
      type and isogenic DeltarpoE strains of V. cholerae, providing additional support
      for the idea that the T2S complex belongs to the sigma(E) regulon. Together, our
      results suggest that the T2S pathway is characterized by the growth phase
      dependent expression of genes encoding cargo proteins and requires a
      multifactorial regulatory network to ensure appropriate kinetics of the secretory
      traffic and the fitness of V. cholerae in different ecological niches. 

PMID- 24733100
TI  - Synthesis and optical properties of water-soluble biperylene-based dendrimers.
AB  - We report the synthesis and photophysical properties of three biperylene-based
      dendrimers, which show red fluorescence in water. A fluorescence microscopy study
      demonstrated uptake of biperylene-based dendrimers in living cells. Our results
      indicate that these biperylene-based dendrimers are promising candidates in
      fluorescence imaging applications with the potential as therapeutic carriers. 

PMID- 24733098
TI  - Enteropathogenic Escherichia coli inhibits type I interferon- and RNase L
      mediated host defense to disrupt intestinal epithelial cell barrier function.
AB  - Enteropathogenic Escherichia coli (EPEC) primarily infects children in developing
      countries and causes diarrhea that can be deadly. EPEC pathogenesis occurs
      through type III secretion system (T3SS)-mediated injection of effectors into
      intestinal epithelial cells (IECs); these effectors alter actin dynamics,
      modulate the immune response, and disrupt tight junction (TJ) integrity. The
      resulting compromised barrier function and increased gastrointestinal (GI)
      permeability may be responsible for the clinical symptoms of infection. Type I
      interferon (IFN) mediates anti-inflammatory activities and serves essential
      functions in intestinal immunity and homeostasis; however, its role in the immune
      response to enteric pathogens, such as EPEC, and its impact on IEC barrier
      function have not been examined. Here, we report that IFN-beta is induced
      following EPEC infection and regulates IEC TJ proteins to maintain barrier
      function. The EPEC T3SS effector NleD counteracts this protective activity by
      inhibiting IFN-beta induction and enhancing tumor necrosis factor alpha to
      promote barrier disruption. The endoribonuclease RNase L is a key mediator of IFN
      induction and action that promotes TJ protein expression and IEC barrier
      integrity. EPEC infection inhibits RNase L in a T3SS-dependent manner, providing
      a mechanism by which EPEC evades IFN-induced antibacterial activities. This work
      identifies novel roles for IFN-beta and RNase L in IEC barrier functions that are
      targeted by EPEC effectors to escape host defense mechanisms and promote
      virulence. The IFN-RNase L axis thus represents a potential therapeutic target
      for enteric infections and GI diseases involving compromised barrier function. 

PMID- 24733099
TI  - Epidemic Clostridium difficile strains demonstrate increased competitive fitness
      compared to nonepidemic isolates.
AB  - Clostridium difficile infection is the most common cause of severe cases of
      antibiotic-associated diarrhea (AAD) and is a significant health burden. Recent
      increases in the rate of C. difficile infection have paralleled the emergence of
      a specific phylogenetic clade of C. difficile strains (ribotype 027; North
      American pulsed-field electrophoresis 1 [NAP1]; restriction endonuclease analysis
      [REA] group BI). Initial reports indicated that ribotype 027 strains were
      associated with increased morbidity and mortality and might be hypervirulent.
      Although subsequent work has raised some doubt as to whether ribotype 027 strains
      are hypervirulent, the strains are considered epidemic isolates that have caused
      severe outbreaks across the globe. We hypothesized that one factor that could
      lead to the increased prevalence of ribotype 027 strains would be if these
      strains had increased competitive fitness compared to strains of other ribotypes.
      We developed a moderate-throughput in vitro model of C. difficile infection and
      used it to test competition between four ribotype 027 clinical isolates and
      clinical isolates of four other ribotypes (001, 002, 014, and 053). We found that
      ribotype 027 strains outcompeted the strains of other ribotypes. A similar
      competitive advantage was observed when two ribotype pairs were competed in a
      mouse model of C. difficile infection. Based upon these results, we conclude that
      one possible mechanism through which ribotype 027 strains have caused outbreaks
      worldwide is their increased ability to compete in the presence of a complex
      microbiota. 

PMID- 24733101
TI  - [Circumcision and orchiopexy: management of complications].
AB  - Circumcision and orchidopexy are among the most frequently performed pediatric
      urological procedures. Although they may be classified as surgical interventions
      suitable for junior surgeons, either procedure can lead to serious consequences
      including the loss of the respective organ. In this paper, the general aspects of
      pediatric urological surgery (e.g., distinctive features of informing underage
      patients, the handling of children in the operating room, and relevant pediatric
      anesthesiological aspects) are described first. Then, the most important sources
      of error will be highlighted and potential complications and their management
      during all stages of the procedure will be illustrated. Apart from the so-called
      freehand circumcision, this paper also deals with potential complications when
      using the Plastibell(r) device. In regard to orchidopexy, laparoscopic procedure
      shall be discussed in addition to the standard procedure. 

PMID- 24733102
TI  - [Clinical significance of and treatment options for increased lipoprotein(a)].
AB  - Lipoprotein(a) has been shown to be associated with an increased incidence of
      cardiovascular diseases for decades. However, only recent research revealed more
      about its physiological function and its role in the development of
      cardiovascular diseases. The authors summarize the physiological role of
      lipoprotein(a), causes and treatment of elevated lipoprotein(a) level, and the
      association between lipoprotein(a) and cardiovascular diseases.

PMID- 24733103
TI  - [What pathomechanisms can lead to stroke in obstructive sleep apnea?].
AB  - One of the less well-documented, potentially modifiable stroke risk factor is the
      obstructive sleep apnea. Obstructive sleep apnea increases cardiovascular
      morbidity and mortality, including stroke risk. The article summarizes the
      pathophysiological factors in sleep apnea syndrome which can increase stroke
      risk.

PMID- 24733104
TI  - [Functional outcome of arthroscopic rotator cuff repair].
AB  - INTRODUCTION: Functional outcome after rotator cuff reconstruction is influenced
      by several factors of which re-rupture is probably the most important. AIM: The
      aim of the study was to evaluate the postoperative outcome including re-rupture
      rate after arthroscopic rotator cuff reconstruction. METHOD: 23 shoulders of 22
      patients were examined prospectively. Physical examination, ultrasound and
      radiography were performed. Quality of life and functional outcome were evaluated
      using Constant Score and Visual Analog Scale. RESULTS: Excellent or good results
      were found in 80% of the patients. The Constant Score has increased from 45 to
      79, and the level of pain decreased from 6.6 to 2.5. Full-thickness rotator cuff
      tear was absent, but partial tear occurred in 7 cases (30%). Average
      acromiohumeral distance in the operated side was 8.5 mm compared to 9.5 mm
      measured on the contralateral shoulder. CONCLUSIONS: Arthroscopic rotator cuff
      repair is a safe and reliable procedure that provides good results.

PMID- 24733105
TI  - [Effect of diabetes on the relation between troponin T and inflammatory markers
      in patients on hemodialysis].
AB  - INTRODUCTION: Cardiac troponin T in renal failure is used for the assessment of
      cardiovascular risk and mortality. Elevated cardiac troponin T levels correlate
      with subclinical myocardial necrosis, coronary heart disease, several
      echocardiographic parameters, metastatic calcification, as well as the presence
      of diabetes and uremic toxins. AIM: The aim of the authors was to examine the
      impact of factors, mainly the independent effects of inflammatory laboratory
      parameters, which may influence hypersensitive troponin T levels in hemodialysed
      patient groups with and without diabetes. METHOD: Hemodialysed patient groups
      with (n = 44) and without diabetes (n = 76) were studied. Difference in serum
      hypersensitive troponin T values before and after dialysis were analysed by
      paired Wilcoxon test. Factors possibly affecting the level of hypersensitive
      troponin T (especially inflammatory markers) were evaluated by multiregression
      analysis. RESULTS: Hypersensitive troponin T levels in patients without diabetes
      (p = 0.0003) and those with diabetes (p = 0.0032) significantly increased during
      hemodialysis. In patients without diabetes several factors had significant effect
      on hypersensitive troponin T including age (p = 0.025), duration of hemodialysis
      (p = 0.0002), presence of cardiovascular complications (p = 0.0002), high
      sensitivity C-reactive protein (p = 0.0021), white blood cell count (p = 0.038),
      and the monocyte ratio (p = 0.0202). However, in patients with diabetes only high
      sensitivity C-reactive protein (p = 0.0024) showed association with
      hypersensitive troponin T levels. CONCLUSIONS: In hemodyalised patients with and
      without diabetes the hypersensitive troponin T levels are differently influenced
      by clinical and inflammatory laboratory parameters, which should be taken into
      consideration during clinical judgement.

PMID- 24733106
TI  - [Prehistory of urology in Hungary -- from lithotomists to Balassa].

PMID- 24733107
TI  - [Scientific evidence in the clinical evaluation of health care delivery and
      health insurance financing].

PMID- 24733108
TI  - Effect of sperm DNA fragmentation on clinical outcome of frozen-thawed embryo
      transfer and on blastocyst formation.
AB  - During the last decades, many studies have shown the possible influence of sperm
      DNA fragmentation on assisted reproductive technique outcomes. However, little is
      known about the impact of sperm DNA fragmentation on the clinical outcome of
      frozen-thawed embryo transfer (FET) from cycles of conventional in vitro
      fertilization (IVF) and intra-cytoplasmic sperm injection (ICSI). In the present
      study, the relationship between sperm DNA fragmentation (SDF) and FET clinical
      outcomes in IVF and ICSI cycles was analyzed. A total of 1082 FET cycles with
      cleavage stage embryos (C-FET) (855 from IVF and 227 from ICSI) and 653 frozen
      thawed blastocyst transfer cycles (B-FET) (525 from IVF and 128 from ICSI) were
      included. There was no significant change in clinical pregnancy, biochemical
      pregnancy and miscarriage rates in the group with a SDF >30% compared with the
      group with a SDF <=30% in IVF and ICSI cycles with C-FET or B-FET. Also, there
      was no significant impact on the FET clinic outcome in IVF and ICSI when
      different values of SDF (such as 10%, 20%, 25%, 35%, and 40%) were taken as
      proposed threshold levels. However, the blastulation rates were significantly
      higher in the SDF <=30% group in ICSI cycle. Taken together, our data show that
      sperm DNA fragmentation measured by Sperm Chromatin Dispersion (SCD) test is not
      associated with clinical outcome of FET in IVF and ICSI. Nonetheless, SDF is
      related to the blastocyst formation in ICSI cycles. 

PMID- 24733109
TI  - Independent mobility and its relationship with moderate-to-vigorous physical
      activity in middle-school Portuguese boys and girls.
AB  - BACKGROUND: The exact relation between objectively measured moderate-to-vigorous
      physical activity (MVPA) and independent mobility in children has yet to be fully
      defined. The objective of this study was to determine whether independent
      mobility is associated with level of MVPA. METHODS: Data were collected from 9
      middle schools in Porto (Portugal) area. A total of 636 children in the 6th grade
      (340 girls and 296 boys) with a mean age of 11.64 years old participated in the
      study. PA was measured in 636 participants using an accelerometer. Multinomial
      logistic regression was applied to assess the odds for belonging to quartiles of
      MVPA. RESULTS: After controlling for age, gender, body mass index, meeting PA
      recommendations, and participation in structured exercise, the odds of having a
      higher level of MVPA when children have higher independent mobility increase
      through the MVPA quartiles. CONCLUSIONS: A positive associations were found
      between independent mobility and quartiles of physical activity.

PMID- 24733110
TI  - Mapping the distinctive populations of lymphatic endothelial cells in different
      zones of human lymph nodes.
AB  - The lymphatic sinuses in human lymph nodes (LNs) are crucial to LN function yet
      their structure remains poorly defined. Much of our current knowledge of
      lymphatic sinuses derives from rodent models, however human LNs differ
      substantially in their sinus structure, most notably due to the presence of
      trabeculae and trabecular lymphatic sinuses that rodent LNs lack. Lymphatic
      sinuses are bounded and traversed by lymphatic endothelial cells (LECs). A better
      understanding of LECs in human LNs is likely to improve our understanding of the
      regulation of cell trafficking within LNs, now an important therapeutic target,
      as well as disease processes that involve lymphatic sinuses. We therefore sought
      to map all the LECs within human LNs using multicolor immunofluorescence
      microscopy to visualize the distribution of a range of putative markers. PROX1
      was the only marker that uniquely identified the LECs lining and traversing all
      the sinuses in human LNs. In contrast, LYVE1 and STAB2 were only expressed by
      LECs in the paracortical and medullary sinuses in the vast majority of LNs
      studied, whilst the subcapsular and trabecular sinuses lacked these molecules.
      These data highlight the existence of at least two distinctive populations of
      LECs within human LNs. Of the other LEC markers, we confirmed VEGFR3 was not
      specific for LECs, and CD144 and CD31 stained both LECs and blood vascular
      endothelial cells (BECs); in contrast, CD59 and CD105 stained BECs but not LECs.
      We also showed that antigen-presenting cells (APCs) in the sinuses could be
      clearly distinguished from LECs by their expression of CD169, and their lack of
      expression of PROX1 and STAB2, or endothelial markers such as CD144. However,
      both LECs and sinus APCs were stained with DCN46, an antibody commonly used to
      detect CD209. 

PMID- 24733111
TI  - Crystal structure of yeast DNA polymerase epsilon catalytic domain.
AB  - DNA polymerase epsilon (Polepsilon) is a multi-subunit polymerase that
      contributes to genomic stability via its roles in leading strand replication and
      the repair of damaged DNA. Here we report the ternary structure of the Polepsilon
      catalytic subunit (Pol2) bound to a nascent G:C base pair (Pol2G:C). Pol2G:C has
      a typical B-family polymerase fold and embraces the template-primer duplex with
      the palm, fingers, thumb and exonuclease domains. The overall arrangement of
      domains is similar to the structure of Pol2T:A reported recently, but there are
      notable differences in their polymerase and exonuclease active sites. In
      particular, we observe Ca2+ ions at both positions A and B in the polymerase
      active site and also observe a Ca2+ at position B of the exonuclease site. We
      find that the contacts to the nascent G:C base pair in the Pol2G:C structure are
      maintained in the Pol2T:A structure and reflect the comparable fidelity of Pol2
      for nascent purine-pyrimidine and pyrimidine-purine base pairs. We note that
      unlike that of Pol3, the shape of the nascent base pair binding pocket in Pol2 is
      modulated from the major grove side by the presence of Tyr431. Together with
      Pol2T:A, our results provide a framework for understanding the structural basis
      of high fidelity DNA synthesis by Pol2. 

PMID- 24733112
TI  - Analysis of the surgical treatment of endobronchial tuberculosis (EBTB).
AB  - PURPOSE: Endobronchial tuberculosis (EBTB) is defined as tuberculosis infection
      of the tracheobronchial tree. EBTB may require aggressive treatment, including
      lung resection, because of severe bronchostenosis and its complications, despite
      formal anti-TB chemotherapy. We present our experience of treating 25 patients
      with EBTB. METHODS: We reviewed retrospectively the medical records of 25
      patients with EBTB treated between 2002 and 2012 at the Department of Thoracic
      Surgery in Beijing Chest Hospital. RESULTS: All 25 patients (5 male, 20 female)
      underwent surgery for fibrostenotic type EBTB. Bronchoscopy showed fibrostenotic
      change in all patients and a cough was the most common symptom. Postoperatively,
      all patients were given anti-TB therapy to take for 6-9 months. CONCLUSIONS: EBTB
      tends to occur at a higher incidence in young women. Surgery may be required for
      severe bronchostenosis and its complications and should be performed for
      symptomatic fibrostenotic type EBTB. During the operation, attention should be
      paid to prevent severe complications and postoperative anti-TB therapy is
      mandatory.

PMID- 24733113
TI  - Comparative evaluation of structural and functional changes in pancreas after
      endoscopic and surgical management of pancreatic necrosis.
AB  - BACKGROUND: Patients with acute necrotizing pancreatitis may develop pancreatic
      insufficiency and this is commonly seen in patients who have undergone surgery
      for pancreatic necrosis. Owing to the paucity of relative data, we
      retrospectively evaluated the structural and functional changes in the pancreas
      after endoscopic and surgical management of pancreatic necrosis. METHODS: The
      records of patients who underwent endoscopic transmural drainage of walled off
      pancreatic necrosis (WOPN) over the last 3 years and who completed at least 6
      months of follow up were analyzed. Structural and functional changes in these
      patients were compared with 25 historical surgical controls (operated in 2005
      2006). RESULTS: Twenty six patients (21 M; mean age 35.4+/-8.1 years) who
      underwent endoscopic drainage for WOPN were followed up for 22.3+/-8.6 months.
      During the follow up, five (19.2%) patients developed diabetes with 3 patients
      requiring insulin and 1 patient with steatorrhea requiring pancreatic enzyme
      supplementation. The pancreatic fluid collection (PFC) recurred in 1 patient
      whose stents spontaneously migrated out. On follow up, in the surgery group, 2
      (8%) patients developed steatorrhea and 11 (44%) developed diabetes. Five (20%)
      of these patients had recurrence of PFC. On comparison of follow up results of
      endoscopic drainage with surgery, recurrence rates as well as frequency of
      endocrine and exocrine insufficiency was lower in the endoscopic group but
      difference was not significant. CONCLUSION: Structural and functional impairment
      of pancreas is seen less frequently in patients with pancreatic necrosis treated
      endoscopically compared to patients undergoing surgery, although the difference
      was insignificant. Further studies with large sample size are needed to confirm
      these initial results.

PMID- 24733114
TI  - Ionic liquid functionalized Janus nanosheets.
AB  - Ionic liquid functionalized Janus nanosheets are synthesized by selective
      treatment of the imidazolin terminated side of Janus nanosheets while the other
      side is preserved. The Janus performance of the nanosheets and thus emulsion
      stability are reversibly triggered by anion exchange. 

PMID- 24733115
TI  - Cation-selective electropreconcentration.
AB  - A cation-selective microfluidic sample preconcentration system is described. The
      cation sample was electropreconcentrated using a reversed-direction
      electroosmotic flow (EOF) and an anion-permselective filter, where an electric
      double layer (EDL) overlap condition existed. The anion-permselective filter
      between microchannels was fabricated by three different methods: 1) extending a
      positively charged, nanoporous, polymer membrane by photopolymerization of
      poly(diallyldimethylammonium chloride) (PDADMAC); 2) etching a nanochannel and
      then coating it with a positively-charged monomer, N-[3-(trimethoxysilyl)propyl]
      N'-(4-vinylbenzyl)ethylenediamine hydrochloride (TMSVE); and, 3) etching a
      nanochannel and then coating it with a positively-charged, pre-formed polymer,
      polyE-323. The EOF direction in the microchannel was reversed by both TMSVE and
      polyE-323 coatings. The cation-selective preconcentration was investigated using
      charged fluorescent dyes and tetramethylrhodamine isothiocyanate (TRITC)-tagged
      peptides/proteins. The preconcentration in the three different systems was
      compared with respect to efficiency, dependence on buffer concentration and pH,
      tolerable flow rate, and sample adsorption. Both TMSVE- and polyE-323-coated
      nanochannels showed robust preconcentration at high flow rates, whereas the
      PDADMAC membrane maintained anion-permselectivity at higher buffer
      concentrations. The TMSVE-coated nanochannels showed a more stable
      preconcentration process, whereas the polyE-323-coated nanochannels showed a
      lower peptide sample adsorption and robust efficiency under a wide range of
      buffer pHs. The system described here can potentially be used for the
      preconcentration of cationic peptides/proteins on microfluidic devices for
      subsequent analyses. 

PMID- 24733116
TI  - An interstitial 4q31.21q31.22 microdeletion associated with developmental delay:
      case report and literature review.
AB  - The 4q deletion syndrome phenotype consists of growth failure and developmental
      delay, minor craniofacial dysmorphism, digital anomalies, and cardiac and
      skeletal defects. We have identified an inversion (inv(1)(q25.2q31.1)) and an
      interstitial deletion in a boy with developmental delay using array-comparative
      genomic hybridization. This de novo deletion is located at 4q31.21q31.22
      (145,963,820- 147,044,764), its size is 0.9-1.1 Mb, and it contains 7 genes
      (ABCE1, OTUD4, SMAD1, MMAA, C4orf51, ZNF827, and ANAPC10) as well as 5
      retrotransposon-derived pseudogenes. Bioinformatic analysis revealed that while
      small copy number variations seem to have no impact on the phenotype, larger
      deletions or duplications in the deleted region are associated with developmental
      delay. Additionally, we found a higher coverage in transposable element sequences
      in the 4q31.21q31.22 region compared to that of the expected repeat density when
      regarding any random genome region. Transposable elements might have contributed
      to the reshaping of the genome architecture and, most importantly, we identified
      3 L1PA family members in the breakpoint regions, suggesting their possible
      contribution in the mechanism underlying the appearance of this deletion. In
      conclusion, this is one of the smallest deletions reported associated with
      developmental delay, and we discuss the possible role of genomic features having
      an impact on the phenotype.

PMID- 24733117
TI  - Transplantation. Erythropoietin inhibits proliferation of human T cells.

PMID- 24733118
TI  - Renal denervation--implications for chronic kidney disease.
AB  - Catheter-based renal denervation to treat patients with resistant hypertension
      and chronic kidney disease (CKD) has generated considerable interest. Data from
      the majority of, but not all, observational studies and randomized controlled
      trials suggest that the procedure does not impair renal function and can
      effectively reduce office and ambulatory blood pressure in patients with primary
      hypertension. The putative beneficial effects of renal denervation seem to result
      from the interruption of renal efferent and afferent nerves. In patients with
      resistant hypertension and CKD, interruption of afferent reflexes might lead to a
      reduction in global sympathetic tone. The subsequent sustained reduction in blood
      pressure is expected to slow the progression of renal disease. However, renal
      denervation might also improve glucose metabolism, increase insulin sensitivity
      and reduce renal inflammation, with renoprotective effects in patients with CKD.
      Additional large randomized controlled trials of renal denervation in
      hypertensive and normotensive patients with CKD are required to precisely define
      the clinical value of the procedure in this population. 

PMID- 24733123
TI  - Adrenergic beta2-receptors mediates visceral hypersensitivity induced by
      heterotypic intermittent stress in rats.
AB  - Chronic visceral pain in patients with irritable bowel syndrome (IBS) has been
      difficult to treat effectively partially because its pathophysiology is not fully
      understood. Recent studies show that norepinephrine (NE) plays an important role
      in the development of visceral hypersensitivity. In this study, we designed to
      investigate the role of adrenergic signaling in visceral hypersensitivity induced
      by heterotypical intermittent stress (HIS). Abdominal withdrawal reflex scores
      (AWRs) used as visceral sensitivity were determined by measuring the visceromoter
      responses to colorectal distension. Colon-specific dorsal root ganglia neurons
      (DRGs) were labeled by injection of DiI into the colon wall and were acutely
      dissociated for whole-cell patch-clamp recordings. Blood plasma level of NE was
      measured using radioimmunoassay kits. The expression of beta2-adrenoceptors was
      measured by western blotting. We showed that HIS-induced visceral
      hypersensitivity was attenuated by systemic administration of a beta-adrenoceptor
      antagonist propranolol, in a dose-dependent manner, but not by a alpha
      adrenoceptor antagonist phentolamine. Using specific beta-adrenoceptor
      antagonists, HIS-induced visceral hypersensitivity was alleviated by beta2
      adrenoceptor antagonist but not by beta1- or beta3-adrenoceptor antagonist.
      Administration of a selective beta2-adrenoceptor antagonist also normalized
      hyperexcitability of colon-innervating DRG neurons of HIS rats. Furthermore,
      administration of beta-adrenoceptor antagonist suppressed sustained potassium
      current density (IK) without any alteration of fast-inactivating potassium
      current density (IA). Conversely, administration of NE enhanced the neuronal
      excitability and produced visceral hypersensitivity in healthy control rats, and
      blocked by beta2-adrenoceptor antagonists. In addition, HIS significantly
      enhanced the NE concentration in the blood plasma but did not change the
      expression of beta2-adrenoceptor in DRGs and the muscularis externa of the colon.
      The present study might provide a potential molecular target for therapy of
      visceral hypersensitivity in patents with IBS. 

PMID- 24733126
TI  - Privileging expands pharmacists' role.

PMID- 24733124
TI  - A rosemary extract rich in carnosic acid selectively modulates caecum microbiota
      and inhibits beta-glucosidase activity, altering fiber and short chain fatty
      acids fecal excretion in lean and obese female rats.
AB  - BACKGROUND: Carnosic acid (CA) and rosemary extracts (RE) show body-weight,
      energy metabolism and inflammation regulatory properties in animal models but the
      mechanisms are not yet understood. Gut microbiota plays an important role in the
      host metabolism and inflammatory status and is modulated by the diet. The aim of
      this research was to investigate whether a RE enriched in CA affected caecum
      microbiota composition and activity in a rat model of genetic obesity. METHODS
      AND PRINCIPAL FINDINGS: A RE (40% CA) was administered with the diet (0.5% w/w)
      to lean (fa/+) and obese (fa/fa) female Zucker rats for 64 days. Changes in the
      microbiota composition and beta-glucosidase activity in the caecum and in the
      levels of macronutrients and short chain fatty acids (SCFA) in feces were
      examined. The RE increased the Blautia coccoides and Bacteroides/Prevotella
      groups and reduced the Lactobacillus/Leuconostoc/Pediococccus group in both types
      of animals. Clostridium leptum was significantly decreased and Bifidobacterium
      increased only in the lean rats. beta-Glucosidase activity was significantly
      reduced and fecal fiber excretion increased in the two genotypes. The RE also
      increased the main SCFA excreted in the feces of the obese rats but decreased
      them in the lean rats reflecting important differences in the uptake and
      metabolism of these molecules between the two genotypes. CONCLUSIONS: Our results
      indicate that the consumption of a RE enriched in CA modifies microbiota
      composition and decreases beta-glucosidase activity in the caecum of female
      Zucker rats while it increases fiber fecal elimination. These results may
      contribute to explain the body weight gain reducing effects of the RE. The
      mutated leptin receptor of the obese animals significantly affects the microbiota
      composition, the SCFA fecal excretion and the host response to the RE intake.

PMID- 24733125
TI  - Mixed effects of elevated pCO2 on fertilisation, larval and juvenile development
      and adult responses in the mobile subtidal scallop Mimachlamys asperrima
      (Lamarck, 1819).
AB  - Ocean acidification is predicted to have severe consequences for calcifying
      marine organisms especially molluscs. Recent studies, however, have found that
      molluscs in marine environments with naturally elevated or fluctuating CO2 or
      with an active, high metabolic rate lifestyle may have a capacity to acclimate
      and be resilient to exposures of elevated environmental pCO2. The aim of this
      study was to determine the effects of near future concentrations of elevated pCO2
      on the larval and adult stages of the mobile doughboy scallop, Mimachlamys
      asperrima from a subtidal and stable physio-chemical environment. It was found
      that fertilisation and the shell length of early larval stages of M. asperrima
      decreased as pCO2 increased, however, there were less pronounced effects of
      elevated pCO2 on the shell length of later larval stages, with high pCO2
      enhancing growth in some instances. Byssal attachment and condition index of
      adult M. asperrima decreased with elevated pCO2, while in contrast there was no
      effect on standard metabolic rate or pHe. The responses of larval and adult M.
      asperrima to elevated pCO2 measured in this study were more moderate than
      responses previously reported for intertidal oysters and mussels. Even this more
      moderate set of responses are still likely to reduce the abundance of M.
      asperrima and potentially other scallop species in the world's oceans at
      predicted future pCO2 levels. 

PMID- 24733127
TI  - Specialty pharmacy presents opportunities for hospitals, health systems.

PMID- 24733128
TI  - CDC says pharmacist-leaders crucial for antimicrobial stewardship.

PMID- 24733129
TI  - Health disparities: Exploring the ethics of orphan drugs.

PMID- 24733130
TI  - FDA application of the USP salt policy.

PMID- 24733131
TI  - Streamlining the residency interview process using Web-based teleconferencing.

PMID- 24733132
TI  - Clinical implications of statin therapy in patients undergoing hemodialysis.
AB  - PURPOSE: The clinical implications regarding the use of statins in patients with
      end-stage renal disease (ESRD) undergoing hemodialysis are explored. SUMMARY: The
      majority of the evidence reviewed from randomized controlled trials and recent
      meta-analyses suggest that there is minimal to no benefit of statin therapy for
      reducing the risk of coronary heart disease (CHD), including cardiovascular
      events and mortality, for statin-naive patients undergoing hemodialysis. The
      Kidney Disease Outcomes Quality Initiative (KDOQI) 2003 dyslipidemia guidelines
      recommended that patients with ESRD receive a statin to reach a goal low-density
      lipoprotein (LDL) cholesterol concentration of <100 mg/dL; however, there was no
      distinction between nondialysis and dialysis patients, and newer evidence has
      since been published. Although KDOQI released 2012 guidelines that recommended
      against the initiation of statins in dialysis patients due to the lack of
      evidence to support benefit, the guidelines were specific for diabetic dialysis
      patients. Clinicians should use their clinical judgment and weigh the risks and
      benefits from the available evidence when deciding whether to initiate statins in
      hemodialysis patients. A statin may be warranted for secondary prevention of
      cardiovascular events or in younger hemodialysis patients who have a longer life
      expectancy. CONCLUSION: The available literature does not support the initiation
      of statins in hemodialysis patients who were not receiving statin therapy before
      requiring hemodialysis. At this time, there are no conclusive data to support
      discontinuation of statins in ESRD patients on hemodialysis receiving statins for
      either primary or secondary prevention of CHD.

PMID- 24733133
TI  - Use of argatroban and catheter-directed thrombolysis with alteplase in an
      oncology patient with heparin-induced thrombocytopenia with thrombosis.
AB  - PURPOSE: The case of an oncology patient who developed heparin-induced
      thrombocytopenia with thrombosis (HITT) and was treated with argatroban plus
      catheter-directed thrombolysis (CDT) with alteplase is presented. SUMMARY: A 63
      year-old Caucasian man with renal amyloidosis undergoing peripheral blood stem
      cell collection for an autologous stem cell transplant developed extensive
      bilateral upper-extremity deep venous thrombosis (DVT) and pulmonary embolism
      secondary to heparin-induced thrombocytopenia. A continuous i.v. infusion of
      argatroban was initiated, and the patient was managed on the general medical
      floor. After one week of therapy, he was transferred to the intensive care unit
      with cardiopulmonary compromise related to superior vena cava (SVC) syndrome. A
      percutaneous mechanical thrombectomy and CDT with alteplase were attempted, but
      the procedure was aborted due to epistaxis. The epistaxis resolved the next day,
      and the patient was restarted on argatroban. A second percutaneous mechanical
      thrombectomy was performed six days later and resulted in partial
      revascularization of the SVC and central veins. Postthrombectomy continuous CDT
      with alteplase was commenced while argatroban was withheld, and complete patency
      of the SVC and central veins was achieved after three days of therapy. Alteplase
      was discontinued, and the patient was reinitiated on argatroban; ultimately, he
      was transitioned to warfarin for long-term anticoagulation. Although the patient
      recovered, he experienced permanent vision and hearing loss, as well as end-stage
      renal disease. CONCLUSION: A 63-year-old man with renal amyloidosis and SVC
      syndrome secondary to HITT was successfully treated with argatroban and CDT with
      alteplase.

PMID- 24733134
TI  - Nalbuphine-induced psychosis treated with naloxone.
AB  - PURPOSE: A case of nalbuphine-induced psychosis, which resolved after the
      administration of naloxone, is described. SUMMARY: A 25-year-old African-American
      woman with a history of systemic lupus erythematosus was admitted to the hospital
      for management of cholecystitis. A laparoscopic cholecystectomy was performed,
      and the patient received multiple doses of i.v. hydromorphone for postoperative
      pain management. Four days later, shortly after receiving a dose of i.v.
      nalbuphine for opioid-induced pruritus, she experienced an acute psychotic event,
      with symptoms including intense headache, akathisia, altered mental status, and
      formication (a hallucinatory sensation of insects crawling on the skin). The
      neuropsychiatric symptoms abated within 5 minutes of two consecutively
      administered doses of i.v. naloxone. During this event, which lasted 25-30
      minutes, there was no evidence of metabolic abnormalities and were no signs of
      infection. The patient did not have a history of mental illness or substance
      abuse. The patient did not receive further doses of nalbuphine and did not
      experience similar events during her hospital stay; she was discharged home 10
      days later without further complications. According to the algorithm of Naranjo
      et al., the case was assigned a score of 6, indicating a probable adverse
      reaction to nalbuphine. CONCLUSION: A patient developed an acute psychotic
      reaction that was probably secondary to administration of i.v. nalbuphine for
      opioid-induced pruritus. Evidence supporting this diagnosis included correlation
      between the timing of administration of nalbuphine and symptom onset and the
      marked improvement in mentation following the administration of naloxone.

PMID- 24733135
TI  - Investigation of pegloticase-associated adverse events from a nationwide
      reporting system database.
AB  - PURPOSE: Pegloticase-associated adverse events reported to the Food and Drug
      Administration Adverse Event Reporting System (FAERS) database in the United
      States were evaluated. METHODS: Retrospective data-mining analysis of FAERS case
      reports listing Krystexxa or pegloticase as the suspect drug and specific adverse
      events (cardiovascular events, infusion-related reactions, gout flares, and
      anaphylaxis) was conducted from the drug's approval date (September 14, 2010)
      through August 27, 2012. Initial and follow-up reports with the same primary
      linked identification number were identified as unique to each patient case. When
      multiple reports for the same patient were identified with a common case number,
      the report with the most recent date was used to eliminate duplicate reports.
      Bayesian confidence propagation neural network methodology was used to identify
      signals of drug-associated adverse events. A potential signal for drug-adverse
      event reports is generated when the lower limit of the 95% two-sided confidence
      interval of the information component is greater than 0. RESULTS: A total of 118
      unique cases of adverse events involving pegloticase in the United States were
      identified during the study period. Fourteen reports were related to pegloticase
      associated cardiovascular events, and 35 were related to pegloticase-associated
      infusion-related reactions. Twenty-six reports were related to pegloticase
      associated gout, and 11 were reports of pegloticase-associated anaphylaxis.
      Bayesian statistics identified potential signals for all pegloticase-associated
      adverse events (cardiovascular events, infusion reactions, gout flares, and
      anaphylaxis). CONCLUSION: Analysis of pegloticase-associated adverse events
      submitted to the FAERS database found that cardiovascular events, infusion
      related reactions, gout flares, and anaphylaxis occurred more frequently than was
      statistically expected.

PMID- 24733137
TI  - The effect of a collaborative pharmacist-hospital care transition program on the
      likelihood of 30-day readmission.
AB  - PURPOSE: The effect of a collaborative pharmacist-hospital care transition
      program on the likelihood of 30-day readmission was evaluated. METHODS: This
      retrospective cohort study was conducted in two acute care hospitals within the
      same hospital system in the southeastern United States. One hospital initiated a
      care transition program in January 2011; the other hospital did not have such a
      program. All patients who were discharged from either hospital to home from
      January 1, 2010, through December 31, 2011, were included in the study. The two
      key program components included bedside delivery of postdischarge medications and
      follow-up telephone calls two to three days after discharge. The likelihood of
      readmission was assessed using multiple logistic regression. RESULTS: Over the 2
      year study period, 19,659 unique patients had 26,781 qualifying index admissions,
      2,523 of which resulted in a readmission within 30 days of discharge. After
      adjusting for various demographic and clinical characteristics, the usual care
      group (i.e., patients who did not participate in the program) had nearly twice
      the odds of readmission within 30 days (odds ratio [OR], 1.90; 95% confidence
      interval [CI], 1.35-2.67), compared with the intervention group (i.e., program
      participants). For patients age 65 years or older, those in the usual care group
      had a sixfold increase in the odds of a 30-day readmission (OR, 6.05; 95% CI,
      1.92-19.00) relative to those in the intervention group. CONCLUSION: A care
      transition program was associated with a lower likelihood of readmission and had
      a greater effect on older patients.

PMID- 24733136
TI  - Polypharmacy with antipsychotic drugs in patients with schizophrenia: trends in
      multiple health care systems.
AB  - PURPOSE: Patterns of pharmacologic treatment in U.S. outpatients with
      schizophrenia across multiple health care settings were investigated. METHODS:
      Antipsychotic drug utilization by patients with schizophrenia and related
      disorders was analyzed using data on 119,662 patients served by the Veterans
      Affairs (VA) health care system in fiscal years 2005-09, data on 5,440 enrollees
      in two health maintenance organizations (HMOs) in 2002-09, and National
      Ambulatory Medical Care Survey (NAMCS) data reflecting the experience of 17.6
      million U.S. residents seeking care outside federal systems during the same eight
      year period. Polypharmacy was defined as the use of more than one antipsychotic
      agent during one year (in the VA sample) or one week (in the HMO and NAMCS
      samples). The association of polypharmacy with hospital admissions was assessed
      via multivariable logistic regression. RESULTS: Rates of antipsychotic use in the
      VA sample ranged from 74% to 78%, with lower and more variable rates in the NAMCS
      sample (69-84%) and the HMO sample (22-67%). VA patients were found to have lower
      polypharmacy rates (20-22%) than patients in the HMO and NAMCS samples (19-31%).
      In all samples evaluated, polypharmacy was associated with an increased
      likelihood of hospital admission (odds ratio range, 1.4-2.4). CONCLUSION: A
      multisystem study revealed that antipsychotic use among patients with
      schizophrenia varied substantially among health care systems and that nearly one
      fifth of patients with schizophrenia or other psychotic disorders in most of the
      health care systems experienced antipsychotic polypharmacy.

PMID- 24733138
TI  - Predictors of naloxone use for respiratory depression and oversedation in
      hospitalized adults.
AB  - PURPOSE: Results of a study to determine the established risk factors most
      closely associated with the use of naloxone to reverse adverse effects of opioid
      analgesia in a hospital population are presented. METHODS: In a retrospective
      case-control study at a community hospital, pharmacy dispensing records were used
      to identify 65 cases over a one-year period that involved the use of naloxone for
      the treatment of oversedation or respiratory depression and met the other
      inclusion criteria; another 65 patients who received opioid analgesia during the
      same period but did not require naloxone were identified as controls. The
      influence of demographics and clinical variables on the likelihood of naloxone
      use was analyzed by linear regression and chisquare testing. RESULTS: Patients in
      the naloxone group had an average of 5 risk factors for opioid-induced
      oversedation or respiratory depression, compared with an average of 3.3 risk
      factors in the control group (p < 0.001). Five factors were significantly
      associated with naloxone use: comorbid renal disease (odds ratio [OR], 6.034; 95%
      confidence interval [CI], 2.565-14.195), cardiac disease (OR, 5.829; 95% CI,
      2.687-12.642), respiratory disease (OR, 3.600; 95% CI, 1.742-7.441), concurrent
      use of central nervous system-sedating medication (OR, 4.750; 95% CI, 1.949
      11.578), and positive smoking status (OR, 4.7421; 95% CI, 2.114-9.256).
      CONCLUSION: Hospitalized patients on general medical units who required naloxone
      to reverse opioid-induced oversedation or respiratory depression had
      significantly more risk factors than matched patients who did not require
      naloxone.

PMID- 24733139
TI  - Building a business plan to support a transplantation pharmacy practice model.

PMID- 24733140
TI  - Incidence and characteristics of injuries during the 2010 FELDA/FAM National
      Futsal League in Malaysia.
AB  - OBJECTIVE: In Malaysia, futsal is a popular sport played by individuals across
      all ages and genders. Despite its popularity, information on futsal related
      injury in Malaysia is not available. The purpose of this study is to examine the
      injury incidence and injury patterns among amateur men and women futsal players
      in Malaysia. METHODS: Players reported injury to the tournament medical team
      during the FELDA/FAM National Futsal League 2010 were interviewed and assessed by
      a Sports Medicine registrar. Player's socio-demographic profiles and information
      about the injury were documented in the injury report form adapted from medical
      report form used by FIFA: Medical Assessment and Research Centre (F-Marc).
      RESULTS: A total of 86 injuries were reported from 141 matches, equivalent to an
      incidence of 91.5 injuries per 1000 player hours (95% CI 72.2 to 110.8), or 61.0
      injuries per 1000 player matches (95% CI 48.1 to 73.9). Most were minor injuries
      resulted from contact with another player. Injuries often involved the lower
      extremity (44%) followed by the trunk (14%) and the upper limb (13%). Ankle (n =
      7; 39%) and knee (n = 6; 33%) sprains were the most prevalent diagnoses of time
      loss injuries. A significant association between time-loss and type of injury was
      found chi2 (1,N = 86) = 3.99, p = 0.04. In addition, time-loss injury was
      significantly associated with playing surface chi2 (1,N = 86) = 10.11, p = 0.018.
      CONCLUSION: The injury rate during the FELDA/FAM National Amateur Futsal Men's
      League in Malaysia was lower compared with previous Futsal World Cups
      competition. Most injuries resulted from contact with another player were minor
      and did not lead to time-loss from participation. Time-loss injury was
      significantly associated with type of injury and playing surface.

PMID- 24733142
TI  - An innovative or disconcerting approach to the psychosocial care of your patient
      with a cardiac condition: are you a lumper or a splitter?

PMID- 24733143
TI  - Screening and Intervention for Comorbid Substance Disorders, PTSD, Depression,
      and Suicide: A Trauma Center Survey.
AB  - OBJECTIVE: Few investigations have examined screening and intervention procedures
      for comorbid substance use and mental disorders at trauma centers in the United
      States, although these disorders are endemic among survivors of traumatic injury.
      In 2006, the American College of Surgeons (ACS) mandated that level I and level
      II trauma centers screen for alcohol use problems and that level I centers
      provide brief intervention for those who screen positive. The ACS is expected to
      recommend best practice policy guidelines for screening for drug use problems and
      posttraumatic stress disorder (PTSD). This study examined screening and
      intervention procedures for the full spectrum of comorbid mental and substance
      use disorders at U.S. trauma centers. METHODS: Respondents at all level I and
      level II trauma centers (N=518) in the United States were asked to complete a
      survey describing screening and intervention procedures for alcohol and drug use
      problems, suicidality, depression, and PTSD. RESULTS: There were 391 (75%)
      respondents. Over 80% of trauma centers routinely screened for alcohol and drug
      use problems. Routine screening and intervention for suicidality, depression, and
      PTSD were markedly less common; in fact, only 7% of centers reported routine
      screening for PTSD. Consistent with ACS policy, level I centers were
      significantly more likely than level II centers to provide alcohol intervention.
      CONCLUSIONS: Alcohol screening and intervention occurred frequently at U.S.
      trauma centers and appeared to be responsive to ACS mandates. In the future,
      efforts to orchestrate clinical investigation and policy could enhance screening
      and intervention procedures for highly prevalent, comorbid mental disorders.

PMID- 24733144
TI  - Asymmetric organocatalytic synthesis of 4,6-bis(1H-indole-3-yl)-piperidine-2
      carboxylates.
AB  - We developed an asymmetric organocatalytic synthesis of 4,6-bis(1H-indole-3-yl)
      piperidine-2-carboxylates using 10 mol% of a chiral phosphoric acid. The
      products, which are novel bisindole-piperidine-amino acid hybrids, can be
      obtained in one step from 3-vinyl indoles with imino esters in dichloromethane at
      room temperature after 1 h of reaction time. A variety of these compounds could
      be synthesized in up to 70% yield and 99% ee, and they were experimentally and
      computationally analyzed regarding their relative and absolute stereochemistry. 

PMID- 24733145
TI  - The environment can explain differences in adolescents' daily physical activity
      levels living in a deprived urban area: cross-sectional study using
      accelerometry, GPS, and focus groups.
AB  - BACKGROUND: Evidence suggests that many contemporary urban environments do not
      support healthy lifestyle choices and are implicated in the obesity pandemic.
      Middlesbrough, in the northeast of England is one such environment and a prime
      target for investigation. METHODS: To measure physical activity (PA) levels in a
      sample of 28 adolescents (aged 11 to 14 years) and describe the environmental
      context of their activity and explore where they are most and least active over a
      7-day period, accelerometry and Global Positioning System (GPS) technology were
      used. Twenty-five of these participants also took part in focus groups about
      their experiences and perceptions of PA engagement. RESULTS: Findings indicated
      that all participants were relatively inactive throughout the observed period
      although bouts of moderate-vigorous physical activity (MVPA) were identified in 4
      contexts: school, home, street, and rural/urban green spaces, with MVPA levels
      highest in the school setting. Providing access to local facilities and services
      (such as leisure centers) is not in itself sufficient to engage adolescents in
      MVPA. CONCLUSION: Factors influencing engagement in MVPA were identified within
      and across contexts, including 'time' as both a facilitator and barrier,
      perceptions of 'gendered' PA, and the social influences of peer groups and family
      members.

PMID- 24733146
TI  - Mapping physician Twitter networks: describing how they work as a first step in
      understanding connectivity, information flow, and message diffusion.
AB  - BACKGROUND: Twitter is becoming an important tool in medicine, but there is
      little information on Twitter metrics. In order to recommend best practices for
      information dissemination and diffusion, it is important to first study and
      analyze the networks. OBJECTIVE: This study describes the characteristics of four
      medical networks, analyzes their theoretical dissemination potential, their
      actual dissemination, and the propagation and distribution of tweets. METHODS:
      Open Twitter data was used to characterize four networks: the American Medical
      Association (AMA), the American Academy of Family Physicians (AAFP), the American
      Academy of Pediatrics (AAP), and the American College of Physicians (ACP). Data
      were collected between July 2012 and September 2012. Visualization was used to
      understand the follower overlap between the groups. Actual flow of the tweets for
      each group was assessed. Tweets were examined using Topsy, a Twitter data
      aggregator. RESULTS: The theoretical information dissemination potential for the
      groups is large. A collective community is emerging, where large percentages of
      individuals are following more than one of the groups. The overlap across groups
      is small, indicating a limited amount of community cohesion and cross
      fertilization. The AMA followers' network is not as active as the other networks.
      The AMA posted the largest number of tweets while the AAP posted the fewest. The
      number of retweets for each organization was low indicating dissemination that is
      far below its potential. CONCLUSIONS: To increase the dissemination potential,
      medical groups should develop a more cohesive community of shared followers.
      Tweet content must be engaging to provide a hook for retweeting and reaching
      potential audience. Next steps call for content analysis, assessment of the
      behavior and actions of the messengers and the recipients, and a larger-scale
      study that considers other medical groups using Twitter.

PMID- 24733147
TI  - The scaling of uphill and downhill locomotion in legged animals.
AB  - Animals must continually respond dynamically as they move through complex
      environments, and slopes are a common terrain on which legged animals must move.
      Despite this, non-level locomotion remains poorly understood. In this study, we
      first review the literature on locomotor mechanics, metabolic cost, and kinematic
      strategies on slopes. Using existing literature we then performed scaling
      analyses of kinematic variables, including speed, duty factor, and stride-length
      across a range of body sizes from ants to horses. The studies that examined
      locomotion on inclines vastly outnumbered those focusing on declines. On
      inclines, animals tend to reduce speed and increase duty factor, but a similar
      consensus could not be reached for declines. Remarkably, stride-length did not
      differ between locomotion on inclines and on level terrain, but this may have
      resulted from data only being available for low slopes (<30 degrees ). On
      declines there appears to be a shift in locomotor strategy that is size
      dependent. At masses <1-10 kg, animals tended to use shorter strides than on
      level terrain, and the opposite occurred at larger body masses. Therefore,
      possibly due to stability issues, body mass plays a significant role in the
      locomotor strategy used when traveling downhill. Although we currently lack
      sufficient data, differential leg function is likely to be critical for
      locomotion on slopes, with mechanical demands differing on limbs during movement
      on level, inclined, and declined surfaces. Our scaling analysis not only
      highlights areas that require future work, but also suggests that body size is
      important for determining the mechanics and strategies animals use to negotiate
      non-level terrain. It is clear that selection has resulted in an incredible range
      of body size among animals, both extant and extinct, and it is likely that the
      ability to move up and down slopes has constrained or relaxed these mechanical
      pressures. Given the lack of integration of ecological data with laboratory
      experiments, future work should first determine which inclines animals actually
      use in nature, as this likely plays a key role in behaviors such as predator-prey
      interactions. 

PMID- 24733148
TI  - A new approach for inversion of large random matrices in massive MIMO systems.
AB  - We report a novel approach for inversion of large random matrices in massive
      Multiple-Input Multiple Output (MIMO) systems. It is based on the concept of
      inverse vectors in which an inverse vector is defined for each column of the
      principal matrix. Such an inverse vector has to satisfy two constraints. Firstly,
      it has to be in the null-space of all the remaining columns. We call it the null
      space problem. Secondly, it has to form a projection of value equal to one in the
      direction of selected column. We term it as the normalization problem. The
      process essentially decomposes the inversion problem and distributes it over
      columns. Each column can be thought of as a node in the network or a particle in
      a swarm seeking its own solution, the inverse vector, which lightens the
      computational load on it. Another benefit of this approach is its applicability
      to all three cases pertaining to a linear system: the fully-determined, the over
      determined, and the under-determined case. It eliminates the need of forming the
      generalized inverse for the last two cases by providing a new way to solve the
      least squares problem and the Moore and Penrose's pseudoinverse problem. The
      approach makes no assumption regarding the size, structure or sparsity of the
      matrix. This makes it fully applicable to much in vogue large random matrices
      arising in massive MIMO systems. Also, the null-space problem opens the door for
      a plethora of methods available in literature for null-space computation to enter
      the realm of matrix inversion. There is even a flexibility of finding an exact or
      approximate inverse depending on the null-space method employed. We employ the
      Householder's null-space method for exact solution and present a complete
      exposition of the new approach. A detailed comparison with well-established
      matrix inversion methods in literature is also given. 

PMID- 24733149
TI  - Gastric non-Hodgkin's lymphoma.

PMID- 24733150
TI  - Single cell growth rate and morphological dynamics revealing an "opportunistic"
      persistence.
AB  - Bacteria persistence is a well-known phenomenon, where a small fraction of cells
      in an isogenic population are able to survive high doses of antibiotic treatment.
      Since the persistence is often associated with single cell behaviour, the ability
      to study the dynamic response of individual cells to antibiotics is critical. In
      this work, we developed a gradient microfluidic system that enables long-term
      tracking of single cell morphology under a wide range of inhibitor
      concentrations. From time-lapse images, we calculated bacterial growth rates
      based on the variations in cell mass and in cell number. Using E. coli and
      Comamonas denitrificans to amoxicillin inhibition as model systems, we found the
      IC50 determined via both methods are in a good agreement. Importantly, the growth
      rates together with morphological dynamics of individual cells has led to the
      discovery of a new form of persistence to amoxicillin. Normal cells that are
      sensitive to amoxicillin gain persistence or recover from the killing process, if
      they have had an opportunity to utilise the cytoplasm released from lysed cells
      close-by. We term this acquired persistence in normal growing cells
      "opportunistic persistence". This finding might shed new insights into biofilm
      resistance and the effect of antibiotics on environmental microbes. 

PMID- 24733151
TI  - Morphological parameters associated with ruptured posterior communicating
      aneurysms.
AB  - The rupture risk of unruptured intracranial aneurysms is known to be dependent on
      the size of the aneurysm. However, the association of morphological
      characteristics with ruptured aneurysms has not been established in a systematic
      and location specific manner for the most common aneurysm locations. We evaluated
      posterior communicating artery (PCoA) aneurysms for morphological parameters
      associated with aneurysm rupture in that location. CT angiograms were evaluated
      to generate 3-D models of the aneurysms and surrounding vasculature. Univariate
      and multivariate analyses were performed to evaluate morphological parameters
      including aneurysm volume, aspect ratio, size ratio, distance to ICA bifurcation,
      aneurysm angle, vessel angles, flow angles, and vessel-to-vessel angles. From
      2005-2012, 148 PCoA aneurysms were treated in a single institution. Preoperative
      CTAs from 63 patients (40 ruptured, 23 unruptured) were available and analyzed.
      Multivariate logistic regression revealed that smaller volume (p = 0.011), larger
      aneurysm neck diameter (0.048), and shorter ICA bifurcation to aneurysm distance
      (p = 0.005) were the most strongly associated with aneurysm rupture after
      adjusting for all other clinical and morphological variables. Multivariate
      subgroup analysis for patients with visualized PCoA demonstrated that larger neck
      diameter (p = 0.018) and shorter ICA bifurcation to aneurysm distance (p = 0.011)
      were significantly associated with rupture. Intracerebral hemorrhage was
      associated with smaller volume, larger maximum height, and smaller aneurysm
      angle, in addition to lateral projection, male sex, and lack of hypertension. We
      found that shorter ICA bifurcation to aneurysm distance is significantly
      associated with PCoA aneurysm rupture. This is a new physically intuitive
      parameter that can be measured easily and therefore be readily applied in
      clinical practice to aid in the evaluation of patients with PCoA aneurysms. 

PMID- 24733152
TI  - Prevalence and risk factors associated with HIV infection, hepatitis and syphilis
      in a state prison of Sao Paulo.
AB  - Given the importance of the control of sexually transmitted infections in the
      general population and specifically in the prison system, we rolled out this
      cross-sectional study in 2007. Standard questionnaires and blood samples were
      accessed among 680 prisoners. The protocol was approved by the Ethics Committee.
      We determined the following seroprevalences: HIV, 1.8% (95%CI = 0.1-3.3); HBV,
      21.0% (95%CI = 17.8-25.1); HBV, 5.3% (95%CI = 3.5-7.6) and syphilis 5.3% (95%CI =
      3.5-7.6). Logistic regression identified significant associations with (p <
      0.05): HIV: injectable drug use (OR = 15.4), age over 30 years (OR = 13.3),
      cocaine use (OR = 5.4) and crack-cocaine use (OR = 5.2); HBV: injectable drug use
      (OR = 3.4), history of previous sexually transmitted infection (OR = 2.3), age
      over 30 years (OR = 1.9) and more than 5 years in prison (OR = 2.2); HCV:
      injectable drug use (OR = 9.65), marijuana use in prison (OR = 2.9) and age over
      30 years (OR = 8.4) and for syphilis: homosexual relationship (OR = 7.8) and
      previous syphilis reported (OR = 7.7). These prevalences remain high when
      compared to the general population, however, HIV infection had decreased compared
      with previous studies in prisoners while the other studied infections remained
      unchanged. Preventive actions to reduce sexual and parenteral risk have been
      advocated. However, measures capable of controlling these infections still have
      not made an impact.

PMID- 24733153
TI  - Determination of the influence of home delivery of HIV therapy on virological
      outcomes and adherence.
AB  - The aim of this study was to evaluate whether the change in the mode of supply of
      HIV medicines to a homecare model was associated with any change in adherence and
      patient outcomes. We conducted a retrospective analysis of medical records of 100
      patients who received supplies from a clinic-based hospital HIV pharmacy and 100
      patients who were started on home delivery over a three-month period and were
      followed up over six months. Data on patient demographics, type of HIV drug
      regimen, HIV viral load, CD4% and adherence status were analysed. The mode of
      delivery had no significant effect on CD4% (p > 0.05), HIV viral load status (p >
      0.05) or adherence status (p > 0.05). There was a significant increase in CD4%
      over time for both groups (p < 0.01). This study suggests that expanding home
      delivery as a model of care in London HIV clinics is safe and does not affect
      adherence and patient outcomes as indicated by HIV viral load and CD4%.

PMID- 24733155
TI  - Nutrition in medical education: from counting hours to measuring competence.

PMID- 24733154
TI  - Colonisation of a phage susceptible Campylobacter jejuni population in two phage
      positive broiler flocks.
AB  - The pathogens Campylobacter jejuni and Campylobacter coli are commensals in the
      poultry intestine and campylobacteriosis is one of the most frequent foodborne
      diseases in developed and developing countries. Phages were identified to be
      effective in reducing intestinal Campylobacter load and this was evaluated, in
      the first field trials which were recently carried out. The aim of this study was
      to further investigate Campylobacter population dynamics during phage application
      on a commercial broiler farm. This study determines the superiority in
      colonisation of a Campylobacter type found in a field trial that was susceptible
      to phages in in vitro tests. The colonisation factors, i.e. motility and gamma
      glutamyl transferase activity, were increased in this type. The clustering in
      phylogenetic comparisons of MALDI-TOF spectra did not match the ST, biochemical
      phenotype and phage susceptibility. Occurrence of Campylobacter jejuni strains
      and phage susceptibility types with different colonisation potential seem to play
      a very important role in the success of phage therapy in commercial broiler
      houses. Thus, mechanisms of both, phage susceptibility and Campylobacter
      colonisation should be further investigated and considered when composing phage
      cocktails. 

PMID- 24733156
TI  - Risk factors for tuberculosis in foreign-born people (FBP) in Italy: a systematic
      review and meta-analysis.
AB  - In Italy, TB notifications in foreign-born people (FBP) are steadily increasing.
      To investigate this issue we did a meta-analysis on risk factors for FBP people.
      A systematic search was performed in PubMed and EMBASE from Jan-1980 to Jan-2013.
      We analysed HIV status, previous TB-treatment, intravenous drug use and alcohol
      abuse, and multidrug resistant TB. Odd ratio was used as a measure of effect. One
      and two-stages approaches were used. In the main analysis we used a 2-stages
      approach to include studies with only aggregate estimates. Among 1996 references,
      18 fulfilled inclusion criteria. In TB-affected FBP people positive HIV-status
      was about 3 times higher than among Italians, after 1996 when combined
      antiretroviral therapy for HIV was introduced (OR: 2.91; 95%CI: 1.37; 6.17). No
      association was found between FBP and intravenous drug users in adults; after 1
      stage meta-analysis foreign born people from highly endemic countries had a 4
      times higher risk to be multidrug resistant TB than Italian people. Finally, TB
      affected FBP were less likely than Italians to be alcoholics (OR: 0.10 95%CI:
      0.01; 0.84) or of having received previous TB-treatment (OR: 0.55; 95%CI: 0.43;
      0.71). An association of multidrug resistant TB with immigrant status as well as
      an association of Tuberculosis with HIV-positive status in foreign-born people
      are major findings of this analysis. Drugs and alcohol abuse do not appear to be
      risk factors for TB in FBP, however they cannot be discharged since may depend on
      cultural traditions and their role may change in the future along with the
      migratory waves. An effective control of TB risk factors among migrants is
      crucial to obtain the goal of TB eradication. 

PMID- 24733157
TI  - Arthroscopic Repair of Full-Thickness Rotator Cuff Tears With and Without
      Acromioplasty: Randomized Prospective Trial With 2-Year Follow-up.
AB  - BACKGROUND: Acromioplasty is commonly performed during arthroscopic rotator cuff
      repair, but its effect on short-term outcomes is debated. PURPOSE: To report the
      short-term clinical outcomes of patients undergoing arthroscopic repair of full
      thickness rotator cuff tears with and without acromioplasty. STUDY DESIGN:
      Randomized controlled trial; Level of evidence, 2. METHODS: Patients undergoing
      arthroscopic repair of full-thickness rotator cuff tears were randomized into
      acromioplasty or nonacromioplasty groups. The Simple Shoulder Test (SST),
      American Shoulder and Elbow Surgeons (ASES) score, Constant score, University of
      California-Los Angeles (UCLA) score, and Short Form-12 (SF-12) health assessment
      were collected along with physical examination including range of motion and
      dynamometer strength testing. Intraoperative data including tear size, repair
      configuration, and concomitant procedures were recorded. Follow-up examination
      was performed at regular intervals up to 2 years. Preoperative imaging was
      reviewed to classify the acromial morphologic type, acromial angle, and lateral
      acromial angulation. RESULTS: A total of 114 patients were initially enrolled in
      the study, and 95 (83%; 43 nonacromioplasty, 52 acromioplasty) were available for
      a minimum 2-year follow-up. There were no significant differences in baseline
      characteristics, including number of tendons torn, repair configuration,
      concomitant procedures, and acromion type and angles. Within groups, there was a
      significant (P < .001) improvement in all functional outcome scores from
      preoperatively to all follow-up time points, including 2 years, for the
      nonacromioplasty and acromioplasty groups (ASES score: 55.1-91.5, 48.8-89.0;
      Constant score: 48.3-75.0, 51.9-78.7, respectively). There were no significant
      differences in functional outcomes between nonacromioplasty and acromioplasty
      groups or between subjects with different acromial features at any time point.
      CONCLUSION: The results of this study demonstrate no difference in clinical
      outcomes after rotator cuff repair with or without acromioplasty at 2 years
      postoperatively.

PMID- 24733158
TI  - Rapid directional change degrades GPS distance measurement validity during
      intermittent intensity running.
AB  - Use of the Global Positioning System (GPS) for quantifying athletic performance
      is common in many team sports. The effect of running velocity on measurement
      validity is well established, but the influence of rapid directional change is
      not well understood in team sport applications. This effect was systematically
      evaluated using multidirectional and curvilinear adaptations of a validated
      soccer simulation protocol that maintained identical velocity profiles. Team
      sport athletes completed 90 min trials of the Loughborough Intermittent Shuttle
      running Test movement pattern on curvilinear, and multidirectional shuttle
      running tracks while wearing a 5 Hz (with interpolated 15 Hz output) GPS device.
      Reference total distance (13 200 m) was systematically over- and underestimated
      during curvilinear (2.61+/-0.80%) and shuttle (-3.17+/-2.46%) trials,
      respectively. Within-epoch measurement uncertainty dispersion was widest during
      the shuttle trial, particularly during the jog and run phases. Relative
      measurement reliability was excellent during both trials (Curvilinear r = 1.00,
      slope = 1.03, ICC = 1.00; Shuttle r = 0.99, slope = 0.97, ICC = 0.99). Absolute
      measurement reliability was superior during the curvilinear trial (Curvilinear
      SEM = 0 m, CV = 2.16%, LOA +/- 223 m; Shuttle SEM = 119 m, CV = 2.44%, LOA +/-
      453 m). Rapid directional change degrades the accuracy and absolute reliability
      of GPS distance measurement, and caution is recommended when using GPS to
      quantify rapid multidirectional movement patterns. 

PMID- 24733159
TI  - Shengmai (a traditional Chinese herbal medicine) for heart failure.
AB  - BACKGROUND: Heart failure is a major public health problem worldwide. Shengmai, a
      traditional Chinese herbal medicine, has long been used as a complementary
      treatment for heart failure in China. This is an update of a Cochrane Review
      published in 2012. OBJECTIVES: To determine the effect (both benefits and harms)
      of Shengmai in treatment of people with heart failure. SEARCH METHODS: We
      searched CENTRAL on The Cochrane Library (Issue 5 of 12, April 2013); DARE on The
      Cochrane Library (Issue 2 of 4, April 2013); MEDLINE (1948 to June Week 1 2013);
      EMBASE (1980 to 2013 Week 23); AMED (1985 to August 2008); BIOSIS (1969 to 7 June
      2013); CBM (1978 to June 2013); VIP (1989 to June 2013); and CNKI (1979 to June
      2013). We also handsearched Chinese journals and did not apply any language
      restrictions. SELECTION CRITERIA: We included randomised controlled trials (RCTs)
      of Shengmai plus usual treatment for heart failure versus usual treatment alone,
      or Shengmai versus placebo, irrespective of blinding status. In this update we
      only included studies with a clear description of randomisation methods and
      classified as true RCTs. DATA COLLECTION AND ANALYSIS: Two authors independently
      selected trials, assessed methodological quality and extracted data. We
      calculated dichotomous data as risk ratios (RRs) and continuous data as mean
      differences (MDs) or standardized mean differences (SMDs) with corresponding 95%
      confidence intervals (CIs). We used a fixed-effect model to perform meta-analysis
      for outcomes without heterogeneity; and a random-effects model to perform meta
      analysis for outcomes with heterogeneity. MAIN RESULTS: We included a total of 14
      RCTs (858 patients) in this review update, four of which were new trials. Of
      these 14 RCTs, 11 trials compared Shengmai plus usual treatment with usual
      treatment alone, and three trials compared Shengmai with placebo. Improvement of
      NYHA functional classification was more common in patients taking Shengmai plus
      usual treatment than in those receiving usual treatment alone (RR 0.37; 95% CI
      0.26 to 0.51; 10 trials, 672 participants; low quality evidence). Beneficial
      effects of Shengmai in treating heart failure were also observed in other
      outcomes, including exercise test, ejection fraction and cardiac output. The
      three RCTs (106 patients) comparing Shengmai with placebo reported improvement in
      NYHA functional classification and in stroke volume. Three of the 14 RCTs
      reported a total of six patients with mild adverse effects and two were withdrawn
      due to the adverse effects. The adverse events rate was 1.21%. AUTHORS'
      CONCLUSIONS: Shengmai may exert a positive effect on heart failure, especially
      for improving NYHA functional classification when Shengmai plus usual treatment
      is used. The review results should be interpreted with caution due to the high
      risk of bias of the included studies (particularly regarding allocation
      concealment and blinding), the small sample size of these studies, and the
      significant heterogeneity in outcomes such as ejection function, cardiac output
      and stroke volume. There was no evidence available concerning the effect of
      Shengmai on mortality, and more high quality studies with long-term follow-up are
      warranted.

PMID- 24733160
TI  - The nucleotide exchange factor SIL1 is required for glucose-stimulated insulin
      secretion from mouse pancreatic beta cells in vivo.
AB  - AIMS/HYPOTHESIS: Regulation of insulin secretion along the secretory pathway is
      incompletely understood. We addressed the expression of SIL1, a nucleotide
      exchange factor for the endoplasmic reticulum (ER) chaperone glucose-regulated
      protein 78 kD (GRP78), in pancreatic beta cells and investigated whether or not
      SIL1 is involved in beta cell function. METHODS: SIL1 expression was analysed by
      immunoblotting and immunofluorescence. Metabolic and islet variables, including
      glucose tolerance, beta cell mass, insulin secretion, islet ultrastructure,
      insulin content and levels of ER stress marker proteins, were addressed in Sil1
      knockout (Sil1 (-/-)) mice. Insulin, proinsulin and C-peptide release was
      addressed in Sil1 (-/-) islets, and SIL1 overexpression or knockdown was explored
      in MIN6 cells in vitro. Models of type 1 diabetes and insulin resistance were
      induced in Sil1 (-/-) mice by administration of streptozotocin (STZ) and a high
      fat diet (HFD), respectively. RESULTS: We show that SIL1 is expressed in
      pancreatic beta cells and is required for islet insulin content, islet sizing,
      glucose tolerance and glucose-stimulated insulin secretion in vivo. Levels of
      pancreatic ER stress markers are increased in Sil1 (-/-) mice, and Sil1 (-/-)
      beta cell ER is ultrastructurally compromised. Isolated Sil1 (-/-) islets show
      lower proinsulin and insulin content and impaired glucose-stimulated insulin
      secretion. Modulation of SIL1 protein levels in MIN6 cells correlates with
      changes in insulin content and secreted insulin. Furthermore, Sil1 (-/-) mice are
      more susceptible to STZ-induced type 1 diabetes with increased apoptosis. Upon
      HFD feeding, Sil1 (-/-) mice show markedly lower insulin secretion and
      exacerbated glucose intolerance compared with control mice. Surprisingly,
      however, HFD-fed Sil1 (-/-) mice display pronounced islet hyperplasia with low
      amounts of insulin in total pancreas. CONCLUSIONS/INTERPRETATION: These results
      reveal a novel role for the nucleotide exchange factor SIL1 in pancreatic beta
      cell function under physiological and disease conditions such as diabetes and the
      metabolic syndrome.

PMID- 24733162
TI  - CotA laccase: high-throughput manipulation and analysis of recombinant enzyme
      libraries expressed in E. coli using droplet-based microfluidics.
AB  - We present a high-throughput droplet-based microfluidic analysis/screening
      platform for directed evolution of CotA laccase: droplet-based microfluidic
      modules were combined to develop an efficient system that allows cell detection
      and sorting based on the enzymatic activity. This platform was run on two
      different operating modes: the "analysis" mode allowing the analysis of the
      enzymatic activity in droplets at very high rates (>1000 Hz) and the "screening"
      mode allowing sorting of active droplets at 400 Hz. The screening mode was
      validated for the directed evolution of the cytoplasmic CotA laccase from B.
      subtilis, a potential interesting thermophilic cathodic catalyst for biofuel
      cells. Single E. coli cells expressing either the active CotA laccase (E. coli
      CotA) or an inactive frameshifted variant (E. coli DeltaCotA) were
      compartmentalized in aqueous droplets containing expression medium. After cell
      growth and protein expression within the droplets, a fluorogenic substrate was
      "picoinjected" in each droplet. Fluorescence-activated droplet sorting was then
      used to sort the droplets containing the desired activity and the corresponding
      cells were then recultivated and identified using colorimetric assays. We
      demonstrated that E. coli CotA cells were enriched 191-fold from a 1 : 9 initial
      ratio of E. coli CotA to E. coli DeltaCotA cells (or 437-fold from a 1 : 99
      initial ratio) using a sorting rate of 400 droplets per s. This system allows
      screening of 10(6) cells in only 4 h, compared to 11 days for screening using
      microtitre plate-based systems. Besides this low error rate sorting mode, the
      system can also be used at higher throughputs in "enrichment" screening mode to
      make an initial purification of a library before further steps of selection.
      Analysis mode, without sorting, was used to rapidly quantify the activity of a
      CotA library constructed using error-prone PCR. This mode allows analysis of
      10(6) cells in only 1.5 h. 

PMID- 24733163
TI  - The hidden genetics of epilepsy-a clinically important new paradigm.
AB  - Understanding the aetiology of epilepsy is essential both for clinical management
      of patients and for conducting neurobiological research that will direct future
      therapies. The aetiology of epilepsy was formerly regarded as unknown in about
      three-quarters of patients; however, massively parallel gene-sequencing studies,
      conducted in a framework of international collaboration, have yielded a bounty of
      discoveries that highlight the importance of gene mutations in the aetiology of
      epilepsy. These data, coupled with clinical genetic studies, suggest a new
      paradigm for use in the clinic: many forms of epilepsy are likely to have a
      genetic basis. Enquiry about a genetic cause of epilepsy is readily overlooked in
      the clinic for a number of understandable but remediable reasons, not least an
      incomplete understanding of its genetic architecture. In addition, the importance
      of de novo mutagenesis is often underappreciated, particularly in the epileptic
      encephalopathies. Other genomic surprises are worth emphasizing, such as the
      emerging evidence of a genetic contribution to focal epilepsies-long regarded as
      acquired conditions-and the complex role of copy number variation. The importance
      of improved understanding of the genetics of the epilepsies is confirmed by the
      positive outcomes, in terms of treatment selection and counselling, of receiving
      a genetic diagnosis. 

PMID- 24733164
TI  - Genetic testing in the epilepsies-developments and dilemmas.
AB  - In the past two decades, the number of genes recognized to have a role in the
      epilepsies has dramatically increased. The availability of testing for epilepsy
      related genes is potentially helpful for clarification of the diagnosis and
      prognosis, selection of optimal treatments, and provision of information for
      family planning. For some patients, identification of a specific genetic cause of
      their epilepsy has important personal value, even in the absence of clear
      clinical utility. The availability of genetic testing also raises new issues that
      have only begun to be considered. These issues include the growing importance of
      educating physicians about when and how to test patients, the need to ensure that
      affected individuals and their families can make informed choices about testing
      and receive support after receiving the results, and the question of what the
      positive and negative consequences of genetic testing will be for affected
      individuals, their family members, and society. 

PMID- 24733166
TI  - State mental health policy: Back to the future: New Mexico returns to the early
      days of Medicaid managed care.
AB  - Gubernatorial administrations in New Mexico have initiated four overhauls of the
      publicly funded behavioral health care system over the past two decades. The most
      recent effort, Centennial Care, was implemented under a Section 1115 Medicaid
      waiver in January 2014. The authors describe Centennial Care, which closely
      resembles the now defunct restructuring of the public system that introduced
      Medicaid managed behavioral health care to the state in 1997. They also note
      disruptions in services to clients and hardships for providers, described locally
      as a "behavioral health crisis," that resulted from actions taken in 2013 by the
      current gubernatorial administration to force the takeover of 15 nonprofit
      service delivery agencies by five Arizona companies. These actions led to an
      onsite investigation by the Centers for Medicare and Medicaid Services.

PMID- 24733165
TI  - Acute ethanol intake induces mitogen-activated protein kinase activation,
      platelet-derived growth factor receptor phosphorylation, and oxidative stress in
      resistance arteries.
AB  - In the present study, we investigated the role of angiotensin type I (AT1)
      receptor in reactive oxygen species (ROS) generation and mitogen-activated
      protein kinases (MAPK) activation induced by acute ethanol intake in resistance
      arteries. We also evaluated the effect of ethanol on platelet-derived growth
      factor receptors (PDGF-R) phosphorylation and the role of this receptor on ROS
      generation by ethanol. Ethanol (1 g/kg; p.o. gavage) effects were assessed within
      30 min in male Wistar rats. Acute ethanol intake did not alter angiotensin I or
      angiotensin II levels in the rat mesenteric arterial bed (MAB). Ethanol induced
      vascular oxidative stress, and this response was not prevented by losartan (10
      mg/kg; p.o. gavage), a selective AT1 receptor antagonist. MAB from ethanol
      treated rats displayed increased SAPK/JNK and PDGF-R phosphorylation, responses
      that were not prevented by losartan. The phosphorylation levels of protein kinase
      B (Akt) and eNOS were not affected by acute ethanol intake. MAB nitrate levels
      and the reactivity of this tissue to acetylcholine, phenylephrine, and sodium
      nitroprusside were not affected by ethanol intake. Ethanol did not alter plasma
      antioxidant capacity, the levels of reduced glutathione, or the activities of
      superoxide dismutase and catalase in the rat MAB. Short-term effects of ethanol
      (50 mmol/l) were evaluated in vascular smooth muscle cells (VSMC) isolated from
      rat MAB. Ethanol increased ROS generation, and this response was not affected by
      AG1296, a PDGF-R inhibitor, or losartan. Finally, ethanol did not alter MAPK or
      PDGF-R phosphorylation in cultured VSMC. Our study provides novel evidence that
      acute ethanol intake induces ROS generation, PDGF-R phosphorylation, and MAPK
      activation through AT(1)-independent mechanisms in resistance arteries in vivo.
      MAPK and PDGF-R play a role in vascular signaling and cardiovascular diseases and
      may contribute to the vascular pathobiology of ethanol. 

PMID- 24733167
TI  - Comparison between RFLP and MIRU-VNTR genotyping of Mycobacterium tuberculosis
      strains isolated in Stockholm 2009 to 2011.
AB  - Our aim was to analyze the difference between methods for genotyping of
      Mycobacterium tuberculosis complex isolates. We collected genotyping results from
      Restriction Fragment Length Polymorphism (RFLP) and Mycobacterial Interspersed
      Repetitive Units-Variable Numbers of Tandem Repeat (MIRU-VNTR) in a
      geographically limited area (Stockholm) during a period of three years. The
      number and proportion of isolates belonging to clusters was reduced by 45 and 35%
      respectively when combining the two methods compared with using RFLP or MIRU-VNTR
      only. The mean size of the clusters was smaller when combining methods and
      smaller with RFLP compared to MIRU-VNTR. In clusters with confirmed
      epidemiological links RFLP coincided slightly better than MIRU-VNTR but where
      there was a difference, the variation in MIRU-VNTR pattern was only in a single
      locus. In isolates with few IS6110 bands in RFLP, MIRU-VNTR differentiated the
      isolates more, dividing the RFLP clusters. Since MIRU-VNTR is faster and less
      labour-intensive it is the method of choice for routine genotyping. In most cases
      it will be sufficient for epidemiological purposes but true clustering might
      still be considered if there are epidemiological links and the MIRU-VNTR results
      differ in only one of its 24 loci.

PMID- 24733168
TI  - In situ generation of sulfoxides with predetermined chirality via a structural
      template with a chiral-at-metal ruthenium complex.
AB  - The reaction of Delta/Lambda-[Ru(bpy)2(py)2](2+) with a prochiral sulfide ligand,
      and then in situ oxidation, provide the corresponding Delta-[Ru(bpy)2{(R)-OSO
      iPr}](+) and Lambda-[Ru(bpy)2{(S)-OSO-iPr}](+) (OSO-iPr = 2
      isopropylsulfonylbenzonate) enantiomers in a yield of 83% with 98% ee. The chiral
      sulfoxides were obtained by treatment of the sulfoxide complexes with TFA in a
      yield of 90% with 88-91% ee. 

PMID- 24733170
TI  - Reply to comments by Kakkar and Dahiya.

PMID- 24733169
TI  - Association of rs6265 and rs2030324 polymorphisms in brain-derived neurotrophic
      factor gene with Alzheimer's disease: a meta-analysis.
AB  - BACKGROUND: The association between polymorphisms rs6265 and rs2030324 in brain
      derived neurotrophic factor (BDNF) and Alzheimer's disease (AD) has been widely
      reported, but the results remain controversial. METHODS: A comprehensive search
      of Pubmed, Web of Science, China National Knowledge Infrastructure (CNKI),
      Wanfang Med Online and China Biology Medical literature database (CBM) was
      performed. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were
      calculated using fixed or random-effects models. We excluded the studies with
      OR>3.0 or OR<0.3 for sensitive analysis. Subgroup analysis by ethnicity, form of
      AD and gender was carried out. Meta-regression was conducted to explore the
      potential sources of between-study heterogeneity. RESULTS: 29 articles with 7548
      cases and 7334 controls concerning rs6265 and 22 articles with 5796 cases and
      5706 controls concerning rs2030324 were included in this meta-analysis. The
      combined evidence suggested rs6265 contributing significantly to the increased
      risk of AD in females (codominant: fixed-effects model (FEM): OR = 1.13, 95% CI =
      1.04-1.23; dominant: FEM: OR = 1.17, 95% CI = 1.05-1.31), especially for
      Caucasian females (codominant: FEM: OR = 1.18, 95% CI = 1.03-1.34; dominant: FEM:
      OR = 1.18, 95% CI = 1.01-1.37) and female late-onset Alzheimer's disease (LOAD)
      patients (codominant: FEM: OR = 1.22, 95% CI = 1.05-1.41; dominant: FEM: OR =
      1.23, 95% CI = 1.03-1.46). No evidence indicated an association between rs2030324
      with AD in codominant (random-effects model (REM): OR = 1.06, 95% CI = 0.89-1.26)
      and dominant (REM: OR = 1.05, 95% CI = 0.86-1.27) models. CONCLUSION: This meta
      analysis suggested A allele of rs6265 might increase the risk of AD in Caucasian
      females and female LOAD patients. In addition, no evidence indicated an
      association between rs2030324 with AD. Further studies are needed to confirm
      these results.

PMID- 24733173
TI  - Colonic polyposis.

PMID- 24733174
TI  - A cyclization-carbonylation-cyclization coupling reaction of (ortho-alkynyl
      phenyl) (methoxymethyl) sulfides with the palladium(II)-bisoxazoline catalyst.
AB  - A cyclization-carbonylation-cyclization coupling reaction (CCC-coupling reaction)
      of (o-alkynylphenyl) (methoxymethyl) sulfides, catalyzed by (box)Pd(II)
      complexes, afforded symmetrical ketones bearing two benzo[b]thiophene groups in
      good to excellent yields. This method is applicable to a broad range of
      substrates. 

PMID- 24733172
TI  - The "brittle response" to Parkinson's disease medications: characterization and
      response to deep brain stimulation.
AB  - OBJECTIVE: Formulate a definition and describe the clinical characteristics of PD
      patients with a "brittle response" (BR) to medications versus a "non-brittle
      response" (NBR), and characterize the use of DBS for this population. METHODS: An
      UF IRB approved protocol used a retrospective chart review of 400 consecutive PD
      patients presenting to the UF Center for Movement Disorders and Neurorestoration.
      Patient records were anonymized and de-identified prior to analysis. SPSS
      statistics were used to analyze data. RESULTS: Of 345 included patients, 19
      (5.5%) met criteria for BR PD. The BR group was comprised of 58% females,
      compared to 29% in the NBR group (P = .008). The former had a mean age of 63.4
      compared to 68.1 in the latter. BR patients had lower mean weight (63.5 vs. 79.6,
      P = <.001), longer mean disease duration (12.6 vs. 8.9 years, P = .003), and had
      been on LD for more years compared to NBR patients (9.8 vs. 5.9, P = .001). UPDRS
      motor scores were higher (40.4 vs. 30.0, P = .001) in BR patients. No differences
      were observed regarding the Schwab and England scale, PDQ-39, and BDI-II. Sixty
      three percent of the BR group had undergone DBS surgery compared to 18% (P =
      .001). Dyskinesias were more common, severe, and more often painful (P = <.001)
      in the BR group. There was an overall positive benefit from DBS. CONCLUSION: BR
      PD occurred more commonly in female patients with a low body weight. Patients
      with longer disease duration and longer duration of LD therapy were also at risk.
      The BR group responded well to DBS.

PMID- 24733175
TI  - Endozoicomonas atrinae sp. nov., isolated from the intestine of a comb pen shell
      Atrina pectinata.
AB  - A novel bacterium, designated strain WP70(T), was isolated from the gut of a comb
      pen shell (Atrina pectinata) collected from the southern sea of Yeosu in Korea.
      The isolate was Gram-stain-negative, aerobic, non-motile and rod-shaped.
      Phylogenetic analyses based on 16S rRNA gene sequences indicated that strain
      WP70(T) belonged to the genus Endozoicomonas. The highest level of sequence
      similarity (98.4%) was shared with Endozoicomonas elysicola MKT110(T). Optimal
      growth occurred in 2% (w/v) NaCl at 30  degrees C and at pH 7. The major cellular
      fatty acids were summed feature 3 (C16 : 1omega7c and/or C16 : 1omega6c), summed
      feature 8 (C18 : 1omega7c and/or C18 : 1omega6c) and C16 : 0. The main
      respiratory quinone was Q-9. The polar lipids comprised phosphatidylglycerol,
      phosphatidylethanolamine, diphosphatidylglycerol, three unidentified
      phospholipids, an unidentified aminolipid, an unidentified aminophospholipid and
      an unidentified lipid. The genomic DNA G+C content was 50.5 mol% and DNA-DNA
      hybridization values indicated <11% genomic relatedness to the closest species.
      Physiological, biochemical, chemotaxonomic and genotypic analyses indicated that
      strain WP70(T) represents a novel species of the genus Endozoicomonas, for which
      the name Endozoicomonas atrinae sp. nov. is proposed. The type strain is WP70(T)
      ( = KACC 17474(T)  = JCM 19190(T)).

PMID- 24733177
TI  - Measuring the impact of "meaningful use" on quality of care.

PMID- 24733176
TI  - Cellulomonas pakistanensis sp. nov., a moderately halotolerant Actinobacteria.
AB  - A rod-shaped, motile, facultatively anaerobic and moderately halotolerant plant
      growth-promoting actinobacterial strain, designated NCCP-11(T), was isolated from
      paddy grains. To delineate its taxonomic position, the strain was subjected to a
      polyphasic characterization. Cells of strain NCCP-11(T) grew at 10-37  degrees C
      (optimum 28-32  degrees C), at pH 6-9 (optimum pH 7) and in 0-12% (w/v) NaCl
      (optimum 1-2%) in broth medium. Based on 16S rRNA gene sequence analysis, strain
      NCCP-11(T) showed highest similarity to the type strains of Cellulomonas hominis
      (98.99%) and Cellulomonas denverensis (98.09 %) and less than 97 % with other
      closely related taxa. The chemotaxonomic data [major menaquinone: MK-9(H4); cell
      wall peptidoglycan: type A4beta; major fatty acids: anteiso-C15 : 0, C16 : 0, C14
      : 0 and anteiso-C17 : 0; major polar lipids: diphosphatidylglycerol,
      phosphatidylinositol, phosphatidylinositolmannosides and two unknown polar
      lipids] also supported the affiliation of strain NCCP-11(T) to the genus
      Cellulomonas. The level of DNA-DNA relatedness between strain NCCP-11(T) and the
      two type strains mentioned above was less than 42.7%. On the basis of DNA-DNA
      relatedness, physiological and biochemical characteristics and phylogenetic
      position, strain NCCP-11(T) can be differentiated from species of the genus
      Cellulomonas with validly published names and thus represents a novel species,
      for which the name Cellulomonas pakistanensis sp. nov. is proposed. The type
      strain is NCCP-11(T) ( = DSM 24792(T) = JCM 18755(T) = KCTC 19798(T)).

PMID- 24733181
TI  - Self-efficacy, physical activity, and sedentary behavior in adolescent girls:
      testing mediating effects of the perceived school and home environment.
AB  - BACKGROUND: According to social-cognitive theory (SCT), self-efficacy affects
      health behavior both directly and indirectly by influencing how individuals
      perceive their environment. This study examines whether perceptions of home and
      school environment mediate the association between self-efficacy and physical
      activity (PA) and sedentary behavior in adolescent girls. METHODS: Baseline data
      from the Nutrition and Enjoyable Activity for Teen Girls (NEAT) was used for this
      study. Grade 8 female students (n = 357) were recruited from 12 secondary schools
      located in low-income communities in the Hunter Region, New South Wales,
      Australia. PA was assessed using accelerometers, and sedentary behavior by self
      report and accelerometers. Self-reported measures were used for perceived home
      and school environment and self-efficacy. Multilevel regression models were
      calculated to determine if the perceived environment mediated the relationship
      between self-efficacy with both PA and sedentary behavior. RESULTS: The
      perceptions of the school and home environment did not mediate the relationship
      between PA self-efficacy and PA behavior or sedentary behavior. CONCLUSION: The
      mediated models were not supported for PA or sedentary behavior. However, other
      results of this paper may be helpful for future theory development and practice.
      More research is needed to understand behaviors in unique populations such as
      this.

PMID- 24733182
TI  - Tendon allograft sterilized by peracetic acid/ethanol combined with gamma
      irradiation.
AB  - BACKGROUND: Research and clinical applications have demonstrated that the effects
      of tendon allografts are comparable to those of autografts when reconstructing
      injured tendons or ligaments, but allograft safety remains problematic.
      Sterilisation could eliminate or decrease the possibility of disease
      transmission, but current methods seldom achieve satisfactory sterilisation
      without affecting the mechanical properties of the tendon. HYPOTHESIS: Peracetic
      acid-ethanol in combination with low-dose gamma irradiation (PE-R) would
      inactivate potential deleterious microorganisms without affecting mechanical and
      biocompatible properties of tendon allograft. STUDY DESIGN: Controlled laboratory
      design. METHODS: HIV, PPV, PRV and BVDV inactivation was evaluated. After
      verifying viral inactivation, the treated tendon allografts were characterised by
      optical microscopy, scanning electron microscopy and tensile testing, and the
      cytocompatibility was assessed with an MTT assay and by subcutaneous
      implantation. RESULTS: Effective and efficient inactivation of HIV, PPV, PRV and
      BVDV was observed. Histological structure and ultrastructure were unchanged in
      the treated tendon allograft, which also exhibited comparable biomechanical
      properties and good biocompatibility. CONCLUSION: The preliminary results
      confirmed our hypothesis and demonstrated that the PE-R tendon allograft has
      significant potential as an alternative to ligament/tendon reconstruction.
      CLINICAL RELEVANCE: Tendon allografts have been extensively used in ligament
      reconstruction and tendon repair. However, current sterilisation methods have
      various shortcomings, so PE-R has been proposed. This study suggests that PE-R
      tendon allograft has great potential as an alternative for ligament/tendon
      reconstruction. WHAT IS KNOWN ABOUT THIS SUBJECT: Sterilisation has been a great
      concern for tendon allografts. However, most sterilisation methods cannot
      inactivate viruses and bacteria without impairing the mechanical properties of
      the tendon allograft. WHAT THIS STUDY ADDS TO EXISTING KNOWLEDGE: Peracetic
      acid/ethanol with gamma irradiation can effectively inactivate viruses and
      bacteria. Meanwhile, tendon allografts sterilised by this method maintain their
      physiological tendon structure, biomechanical integrity and good compatibility.

PMID- 24733183
TI  - Drosophila microbiota modulates host metabolic gene expression via IMD/NF-kappaB
      signaling.
AB  - Most metazoans engage in mutualistic interactions with their intestinal
      microbiota. Despite recent progress the molecular mechanisms through which
      microbiota exerts its beneficial influences on host physiology are still largely
      uncharacterized. Here we use axenic Drosophila melanogaster adults associated
      with a standardized microbiota composed of a defined set of commensal bacterial
      strains to study the impact of microbiota association on its host transcriptome.
      Our results demonstrate that Drosophila microbiota has a marked impact on the
      midgut transcriptome and promotes the expression of genes involved in host
      digestive functions and primary metabolism. We identify the IMD/Relish signaling
      pathway as a central regulator of this microbiota-mediated transcriptional
      response and we reveal a marked transcriptional trade-off between the midgut
      response to its beneficial microbiota and to bacterial pathogens. Taken together
      our results indicate that microbiota association potentiates host nutrition and
      host metabolic state, two key physiological parameters influencing host fitness.
      Our work paves the way to subsequent mechanistic studies to reveal how these
      microbiota-dependent transcriptional signatures translate into host physiological
      benefits. 

PMID- 24733184
TI  - Elimination of inter-domain interactions increases the cleavage fidelity of the
      restriction endonuclease DraIII.
AB  - DraIII is a type IIP restriction endonucleases (REases) that recognizes and
      creates a double strand break within the gapped palindromic sequence CAC?NNN?GTG
      of double-stranded DNA (? indicates nicking on the bottom strand; ? indicates
      nicking on the top strand). However, wild type DraIII shows significant star
      activity. In this study, it was found that the prominent star site is
      CAT?GTT?GTG, consisting of a star 5' half (CAT) and a canonical 3' half (GTG).
      DraIII nicks the 3' canonical half site at a faster rate than the 5' star half
      site, in contrast to the similar rate with the canonical full site. The crystal
      structure of the DraIII protein was solved. It indicated, as supported by
      mutagenesis, that DraIII possesses a betabetaalpha-metal HNH active site. The
      structure revealed extensive intra-molecular interactions between the N-terminal
      domain and the C-terminal domain containing the HNH active site. Disruptions of
      these interactions through site-directed mutagenesis drastically increased
      cleavage fidelity. The understanding of fidelity mechanisms will enable
      generation of high fidelity REases. 

PMID- 24733185
TI  - Simultaneous voltammetric determination of dopamine and epinephrine in human body
      fluid samples using a glassy carbon electrode modified with nickel oxide
      nanoparticles and carbon nanotubes within a dihexadecylphosphate film.
AB  - A simple and highly selective electrochemical method was developed for the single
      or simultaneous determination of dopamine (DA) and epinephrine (EP) in human body
      fluids using a glassy carbon electrode modified with nickel oxide nanoparticles
      and carbon nanotubes within a dihexadecylphosphate film using square-wave
      voltammetry (SWV) or differential-pulse voltammetry (DPV). Using DPV with the
      proposed electrode, a separation of ca. 360 mV between the peak reduction
      potentials of DA and EP present in binary mixtures was obtained. The analytical
      curves for the simultaneous determination of dopamine and epinephrine showed an
      excellent linear response, ranging from 7.0 * 10(-8) to 4.8 * 10(-6) and 3.0 *
      10(-7) to 9.5 * 10(-6) mol L(-1) for DA and EP, respectively. The detection
      limits for the simultaneous determination of DA and EP were 5.0 * 10(-8) mol L(
      1) and 8.2 * 10(-8) mol L(-1), respectively. The proposed method was successfully
      applied in the simultaneous determination of these analytes in human body fluid
      samples of cerebrospinal fluid, human serum and lung fluid. 

PMID- 24733186
TI  - Co-transplantation of endothelial progenitor cells and pancreatic islets to
      induce long-lasting normoglycemia in streptozotocin-treated diabetic rats.
AB  - Graft vascularization is a crucial step to obtain stable normoglycemia in
      pancreatic islet transplantation. Endothelial progenitor cells (EPCs) contribute
      to neoangiogenesis and to the revascularization process during ischaemic events
      and play a key role in the response to pancreatic islet injury. In this work we
      co-transplanted EPCs and islets in the portal vein of chemically-induced diabetic
      rats to restore islet vascularization and to improve graft survival. Syngenic
      islets were transplanted, either alone or with EPCs derived from green
      fluorescent protein (GFP) transgenic rats, into the portal vein of streptozotocin
      induced diabetic rats. Blood glucose levels were monitored and intraperitoneal
      glucose tolerance tests were performed. Real time-PCR was carried out to evaluate
      the gene expression of angiogenic factors. Diabetic-induced rats showed long
      lasting (6 months) normoglycemia upon co-transplantation of syngenic islets and
      EPCs. After 3-5 days from transplantation, hyperglycaemic levels dropped to
      normal values and lasted unmodified as long as they were checked. Further,
      glucose tolerance tests revealed the animals' ability to produce insulin on
      demand as indexed by a prompt response in blood glucose clearance. Graft
      neovascularization was evaluated by immunohistochemistry: for the first time the
      measure of endothelial thickness revealed a donor-EPC-related neovascularization
      supporting viable islets up to six months after transplant. Our results highlight
      the importance of a newly formed viable vascular network together with pancreatic
      islets to provide de novo adequate supply in order to obtain enduring
      normoglycemia and prevent diabetes-related long-term health hazards. 

PMID- 24733187
TI  - Novel identification of Dermacentor variabilis Arp2/3 complex and its role in
      rickettsial infection of the arthropod vector.
AB  - Tick-borne spotted fever group (SFG) Rickettsia species must be able to infect
      both vertebrate and arthropod host cells. The host actin-related protein 2/3
      (Arp2/3) complex is important in the invasion process and actin-based motility
      for several intracellular bacteria, including SFG Rickettsia in Drosophila and
      mammalian cells. To investigate the role of the tick Arp2/3 complex in tick
      Rickettsia interactions, open reading frames of all subunits of the protein
      including Arp2, Arp3, ARPC1, ARPC2, ARPC3, ARPC4, and ARPC5 were identified from
      Dermacentor variabilis. Amino acid sequence analysis showed variation (ranging
      from 25-88%) in percent identity compared to the corresponding subunits of the
      complex from Drosophila melanogaster, Mus musculus, Homo sapiens, and
      Saccharomyces cerevisiae. Potential ATP binding sites were identified in D.
      variabilis (Dv) Arp2 and Arp3 subunits as well as five putative WD (Trp-Asp)
      motifs which were observed in DvARPC1. Transcriptional profiles of all subunits
      of the DvArp2/3 complex revealed greater mRNA expression in both Rickettsia
      infected and -uninfected ovary compared to midgut and salivary glands. In
      response to R. montanensis infection of the tick ovary, the mRNA level of only
      DvARPC4 was significantly upregulated compared to uninfected tissues. Arp2/3
      complex inhibition bioassays resulted in a decrease in the ability of R.
      montanensis to invade tick tissues with a significant difference in the tick
      ovary, indicating a role for the Arp2/3 complex in rickettsial invasion of tick
      cells. Characterization of tick-derived molecules associated with rickettsial
      infection is imperative in order to better comprehend the ecology of tick-borne
      rickettsial diseases. 

PMID- 24733188
TI  - Haloferax volcanii, a prokaryotic species that does not use the Shine Dalgarno
      mechanism for translation initiation at 5'-UTRs.
AB  - It was long assumed that translation initiation in prokaryotes generally occurs
      via the so-called Shine Dalgarno (SD) mechanism. Recently, it became clear that
      translation initiation in prokaryotes is more heterogeneous. In the haloarchaeon
      Haloferax volcanii, the majority of transcripts is leaderless and most
      transcripts with a 5'-UTR lack a SD motif. Nevertheless, a bioinformatic analysis
      predicted that 20-30% of all genes are preceded by a SD motif in haloarchaea. To
      analyze the importance of the SD mechanism for translation initiation in
      haloarchaea experimentally the monocistronic sod gene was chosen, which contains
      a 5'-UTR with an extensive SD motif of seven nucleotides and a length of 19 nt,
      the average length of 5'UTRs in this organism. A translational fusion of part of
      the sod gene with the dhfr reporter gene was constructed. A mutant series was
      generated that matched the SD motif from zero to eight positions, respectively.
      Surprisingly, there was no correlation between the base pairing ability between
      transcripts and 16S rRNA and translational efficiency in vivo under several
      different growth conditions. Furthermore, complete replacement of the SD motif by
      three unrelated sequences did not reduce translational efficiency. The results
      indicate that H. volcanii does not make use of the SD mechanism for translation
      initiation in 5'-UTRs. A genome analysis revealed that while the number of SD
      motifs in 5'-UTRs is rare, their fraction within open reading frames is high.
      Possible biological functions for intragenic SD motifs are discussed, including
      re-initiation of translation at distal genes in operons. 

PMID- 24733189
TI  - High glucose induces CCL20 in proximal tubular cells via activation of the KCa3.1
      channel.
AB  - BACKGROUND: Inflammation plays a key role in the development and progression of
      diabetic nephropathy (DN). KCa3.1, a calcium activated potassium channel protein,
      is associated with vascular inflammation, atherogenesis, and proliferation of
      endothelial cells, macrophages, and fibroblasts. We have previously demonstrated
      that the KCa3.1 channel is activated by TGF-beta1 and blockade of KCa3.1
      ameliorates renal fibrotic responses in DN through inhibition of the TGF-beta1
      pathway. The present study aimed to identify the role of KCa3.1 in the
      inflammatory responses inherent in DN. METHODS: Human proximal tubular cells (HK2
      cells) were exposed to high glucose (HG) in the presence or absence of the KCa3.1
      inhibitor TRAM34 for 6 days. The proinflammatory cytokine chemokine (C-C motif)
      ligand 20 (CCL20) expression was examined by real-time PCR and enzyme-linked
      immunosorbent assay (ELISA). The activity of nuclear factor-kappaB (NF-kappaB)
      was measured by nuclear extraction and electrophoretic mobility shift assay
      (EMSA). In vivo, the expression of CCL20, the activity of NF-kappaB and
      macrophage infiltration (CD68 positive cells) were examined by real-time PCR
      and/or immunohistochemistry staining in kidneys from diabetic or KCa3.1-/- mice,
      and in eNOS-/- diabetic mice treated with the KCa3.1 channel inhibitor TRAM34.
      RESULTS: In vitro data showed that TRAM34 inhibited CCL20 expression and NF
      kappaB activation induced by HG in HK2 cells. Both mRNA and protein levels of
      CCL20 significantly decreased in kidneys of diabetic KCa3.1-/- mice compared to
      diabetic wild type mice. Similarly, TRAM34 reduced CCL20 expression and NF-kappaB
      activation in diabetic eNOS-/- mice compared to diabetic controls. Blocking the
      KCa3.1 channel in both animal models led to a reduction in phosphorylated NF
      kappaB. CONCLUSIONS: Overexpression of CCL20 in human proximal tubular cells is
      inhibited by blockade of KCa3.1 under diabetic conditions through inhibition of
      the NF-kappaB pathway.

PMID- 24733190
TI  - A flexible urban health index for small area disparities.
AB  - Available urban health metrics focus primarily on large area rankings. Less has
      been done to develop an index that provides information about level of health and
      health disparities for small geographic areas. Adopting a method used by the
      Human Development Index, we standardized indicators for small area units on a (0,
      1) interval and combined them using their geometric mean to form an Urban Health
      Index (UHI). Disparities were assessed using the ratio of the highest to lowest
      decile and measurement of the slope of the eight middle deciles (middle; 80 %) of
      the data. We examined the sensitivity of the measure to weighting, to changes in
      the method, to correlation among indicators, and to substitution of indicators.
      Using seven health determinants and applying these methods to the 128 census
      tracts in the city of Atlanta, USA, we found a disparity ratio of 5.92 and a
      disparity slope of 0.54, suggesting substantial inequality and heterogeneity of
      risk. The component indicators were highly correlated; their systematic removal
      had a small effect on the results. Except in extreme cases, weighting had a
      little effect on the rankings. A map of Atlanta census tracts exposed a swath of
      high disparity. UHI rankings, ratio, and slope were resistant to alteration in
      composition and to non-extreme weighting schemes. This empirical evaluation was
      limited to a single realization, but suggests that a flexible tool, whose method
      rather than content is standardized, may be of use for local evaluation, for
      decision making, and for area comparison. 

PMID- 24733191
TI  - Comparison of Tripterygium wilfordii Hook F with methotrexate in the treatment of
      active rheumatoid arthritis (TRIFRA): a randomised, controlled clinical trial.
AB  - OBJECTIVES: To compare the efficacy and safety of Tripterygium wilfordii Hook F
      (TwHF) with methotrexate (MTX) in the treatment of active rheumatoid arthritis
      (RA). METHODS: Design: a multicentre, open-label, randomised controlled trial.
      All patients were assessed by trained investigators who were unaware of the
      therapeutic regimen. INTERVENTION: 207 patients with active RA were randomly
      allocated (1:1:1) to treatment with MTX 12.5 mg once a week, or TwHF 20 mg three
      times a day, or the two in combination. At week 12, if reduction of the 28-joint
      count Disease Activity Score (DAS28) was <30% in the monotherapy groups, the
      patient was switched to MTX+TwHF. The primary efficacy point was the proportion
      of patients achieving an American College of Rheumatology (ACR) 50 response at
      week 24. RESULTS: 174/207 (84.1%) patients completed 24 weeks of the trial. In an
      intention-to-treat analysis, the proportion of patients reaching the ACR50
      response criteria was 46.4% (32/69), 55.1% (38/69) and 76.8% (53/69),
      respectively, in the MTX, TwHF and MTX+TwHF groups (TwHF vs MTX monotherapy,
      p=0.014; MTX+TwHF vs MTX monotherapy, p<0.001). Similar statistically significant
      patterns at week 24 were found for ACR20, ACR70, clinical Disease Activity Index
      good responses, EULAR good response, remission rate and low disease activity
      rate. Significant improvement in the Health Assessment Questionnaire and 36-item
      Short-Form Health Survey questionnaire scores from baseline to week 24 was seen
      in each treatment arm (p<0.05), though no significant difference was found among
      the treatment arms (p>0.05). The result of per-protocol analysis agreed with that
      seen in the intention-to-treat analysis. Seven, three and five women in the TwHF,
      MTX and combination groups, respectively, developed irregular menstruation (TwHF
      vs MTX monotherapy, p=0.216). CONCLUSIONS: TwHF monotherapy was not inferior to,
      and MTX+TwHF was better than, MTX monotherapy in controlling disease activity in
      patients with active RA. TRIAL REGISTRATION NUMBER: NCT01613079.

PMID- 24733192
TI  - Trends in prevalence and control of diabetes in the United States, 1988-1994 and
      1999-2010.
AB  - BACKGROUND: Trends in the prevalence and control of diabetes defined by
      hemoglobin A1c (HbA1c) levels are important for health care policy and planning.
      OBJECTIVE: To update trends in the prevalence of diabetes, prediabetes, and
      glycemic control. DESIGN: Cross-sectional. SETTING: NHANES (National Health and
      Nutrition Examination Survey) in 1988-1994 and 1999-2010. PARTICIPANTS: Adults
      aged 20 years or older. MEASUREMENTS: We used calibrated HbA1c levels to define
      undiagnosed diabetes (>=6.5%); prediabetes (5.7% to 6.4%); and, among persons
      with diagnosed diabetes, glycemic control (<7.0% or <8.0%). Trends in HbA1c
      categories were compared with fasting glucose levels (>=7.0 mmol/L [>=126 mg/dL]
      and 5.6 to 6.9 mmol/L [100 to 125 mg/dL]). RESULTS: In 2010, approximately 21
      million U.S. adults aged 20 years or older had total confirmed diabetes (self
      reported diabetes or diagnostic levels for both fasting glucose and calibrated
      HbA1c). During 2 decades, the prevalence of total confirmed diabetes increased,
      but the prevalence of undiagnosed diabetes remained fairly stable, reducing the
      proportion of total diabetes cases that are undiagnosed to 11% in 2005-2010. The
      prevalence of prediabetes was lower when defined by calibrated HbA1c levels than
      when defined by fasting glucose levels but has increased from 5.8% in 1988-1994
      to 12.4% in 2005-2010 when defined by HbA1c levels. Glycemic control improved
      overall, but total diabetes prevalence was greater and diabetes was less
      controlled among non-Hispanic blacks and Mexican Americans compared with non
      Hispanic whites. LIMITATION: Cross-sectional design. CONCLUSION: Over the past 2
      decades, the prevalence of total diabetes has increased substantially. However,
      the proportion of undiagnosed diabetes cases decreased, suggesting improvements
      in screening and diagnosis. Among the growing number of persons with diagnosed
      diabetes, glycemic control improved but remains a challenge, particularly among
      non-Hispanic blacks and Mexican Americans. PRIMARY FUNDING SOURCE: National
      Institutes of Health.

PMID- 24733193
TI  - The CAM-S: development and validation of a new scoring system for delirium
      severity in 2 cohorts.
AB  - BACKGROUND: Quantifying the severity of delirium is essential to advancing
      clinical care by improved understanding of delirium effect, prognosis,
      pathophysiology, and response to treatment. OBJECTIVE: To develop and validate a
      new delirium severity measure (CAM-S) based on the Confusion Assessment Method.
      DESIGN: Validation analysis in 2 independent cohorts. SETTING: Three academic
      medical centers. PATIENTS: The first cohort included 300 patients aged 70 years
      or older scheduled for major surgery. The second included 919 medical patients
      aged 70 years or older. MEASUREMENTS: A 4-item short form and a 10-item long form
      were developed. Association of the maximum CAM-S score during hospitalization
      with hospital and posthospital outcomes related to delirium was evaluated.
      RESULTS: Representative results included adjusted mean length of stay, which
      increased across levels of short-form severity from 6.5 days (95% CI, 6.2 to 6.9
      days) to 12.7 days (CI, 11.2 to 14.3 days) (P for trend < 0.001) and across
      levels of long-form severity from 5.6 days (CI, 5.1 to 6.1 days) to 11.9 days
      (CI, 10.8 to 12.9 days) (P for trend < 0.001). Representative results for the
      composite outcome of adjusted relative risk of death or nursing home residence at
      90 days increased progressively across levels of short-form severity from 1.0
      (referent) to 2.5 (CI, 1.9 to 3.3) (P for trend < 0.001) and across levels of
      long-form severity from 1.0 (referent) to 2.5 (CI, 1.6 to 3.7) (P for trend <
      0.001). LIMITATION: Data on clinical outcomes were measured in an older data set
      limited to patients aged 70 years or older. CONCLUSION: The CAM-S provides a new
      delirium severity measure with strong psychometric properties and strong
      associations with important clinical outcomes. PRIMARY FUNDING SOURCE: National
      Institute on Aging.

PMID- 24733194
TI  - Virtual autopsy with multiphase postmortem computed tomographic angiography
      versus traditional medical autopsy to investigate unexpected deaths of
      hospitalized patients: a cohort study.
AB  - BACKGROUND: "Virtual" autopsy by postmortem computed tomography (PMCT) can
      replace medical autopsy to a certain extent but has limitations for
      cardiovascular diseases. These limitations might be overcome by adding multiphase
      PMCT angiography. OBJECTIVE: To compare virtual autopsy by multiphase PMCT
      angiography with medical autopsy. DESIGN: Prospective cohort study.
      (ClinicalTrials.gov: NCT01541995) SETTING: Single-center study at the University
      Medical Center Hamburg-Eppendorf, Hamburg, Germany, between 1 April 2012 and 31
      March 2013. PATIENTS: Hospitalized patients who died unexpectedly or within 48
      hours of an event necessitating cardiopulmonary resuscitation. MEASUREMENTS:
      Diagnoses from clinical records were compared with findings from both types of
      autopsy. New diagnoses identified by autopsy were classified as major or minor,
      depending on whether they would have altered clinical management. RESULTS: Of 143
      eligible patients, 50 (35%) had virtual and medical autopsy. Virtual autopsy
      confirmed 93% of all 336 diagnoses identified from antemortem medical records,
      and medical autopsy confirmed 80%. In addition, virtual and medical autopsy
      identified 16 new major and 238 new minor diagnoses. Seventy-three of the virtual
      autopsy diagnoses, including 32 cases of coronary artery stenosis, were
      identified solely by multiphase PMCT angiography. Of the 114 clinical diagnoses
      classified as cardiovascular, 110 were confirmed by virtual autopsy and 107 by
      medical autopsy. In 11 cases, multiphase PMCT angiography showed "unspecific
      filling defects," which were not reported by medical autopsy. LIMITATION: These
      results come from a single center with concerted interest and expertise in
      postmortem imaging; further studies are thus needed for generalization.
      CONCLUSION: In cases of unexpected death, the addition of multiphase PMCT
      angiography increases the value of virtual autopsy, making it a feasible
      alternative for quality control and identification of diagnoses traditionally
      made by medical autopsy. PRIMARY FUNDING SOURCE: University Medical Center
      Hamburg-Eppendorf.

PMID- 24733195
TI  - High-energy extracorporeal shock-wave therapy for treating chronic calcific
      tendinitis of the shoulder: a systematic review.
AB  - BACKGROUND: Calcific and noncalcific tendinitis of the shoulder can be
      unresponsive to conventional therapies. Extracorporeal shock-wave therapy (ESWT)
      has been suggested as an alternative treatment. PURPOSE: To assess the efficacy
      of ESWT in patients with calcific and noncalcific tendinitis. DATA SOURCES:
      MEDLINE, Cochrane Central Register of Controlled Trials, EMBASE, Web of Science,
      and Google Scholar were searched up to 1 November 2013. STUDY SELECTION:
      Randomized, controlled trials (RCTs) comparing high-energy versus low-energy ESWT
      or placebo for treatment of calcific or noncalcific tendinitis of the shoulder.
      Outcome measures included pain (visual analogue scale score), functional
      assessment (Constant-Murley score), and resolution of calcifications. DATA
      EXTRACTION: Three independent reviewers abstracted data and determined
      eligibility and quality by consensus. DATA SYNTHESIS: Twenty-eight RCTs met the
      inclusion criteria. Studies were heterogeneous. Twenty RCTs compared ESWT energy
      levels and placebo and consistently showed that high-energy ESWT was
      significantly better than placebo in decreasing pain and improving function and
      resorption of calcifications in calcific tendinitis. No significant difference
      was found between ESWT and placebo in treatment of noncalcific tendinitis.
      LIMITATION: The number of RCTs was small, and the studies were heterogeneous.
      CONCLUSION: High-energy ESWT is effective for improving pain and shoulder
      function in chronic calcific shoulder tendinitis and can result in complete
      resolution of calcifications. This therapy may be underutilized for a condition
      that can be difficult to manage. PRIMARY FUNDING SOURCE: None.

PMID- 24733196
TI  - Diagnostic accuracy of point-of-care tests for detecting albuminuria: a
      systematic review and meta-analysis.
AB  - BACKGROUND: Experts recommend screening for albuminuria in patients at risk for
      kidney disease. PURPOSE: To systematically review evidence about the diagnostic
      accuracy of point-of-care (POC) tests for detecting albuminuria in individuals
      for whom guidelines recommend such detection. DATA SOURCES: Cochrane Library,
      EMBASE, Medion database, MEDLINE, and Science Citation Index from 1963 through 5
      December 2013; hand searches of other relevant journals; and reference lists.
      STUDY SELECTION: Cross-sectional studies, published in any language, that
      compared the accuracy of machine-read POC tests of urinary albumin-creatinine
      ratio with that of laboratory measurement. DATA EXTRACTION: Two independent
      reviewers extracted study data and assessed study quality using the QUADAS-2
      (Quality Assessment of Diagnostic Accuracy Studies 2) tool. DATA SYNTHESIS:
      Sixteen studies (n = 3356 patients) that evaluated semiquantitative or
      quantitative POC tests and used random urine samples collected in primary or
      secondary ambulatory care settings met inclusion criteria. Pooling results from a
      bivariate random-effects model gave sensitivity and specificity estimates of 76%
      (95% CI, 63% to 86%) and 93% (CI, 84% to 97%), respectively, for the
      semiquantitative test. Sensitivity and specificity estimates for the quantitative
      test were 96% (CI, 78% to 99%) and 98% (CI, 93% to 99%), respectively. The
      negative likelihood ratios for the semiquantitative and quantitative tests were
      0.26 (CI, 0.16 to 0.40) and 0.04 (CI, 0.01 to 0.25), respectively. LIMITATION:
      Accuracy estimates were based on data from single-sample urine measurement, but
      guidelines require that diagnosis of albuminuria be based on at least 2 of 3
      samples collected in a 6-month period. CONCLUSION: A negative semiquantitative
      POC test result does not rule out albuminuria, whereas quantitative POC testing
      meets required performance standards and can be used to rule out albuminuria.
      PRIMARY FUNDING SOURCE: None.

PMID- 24733199
TI  - Value-based payment for physicians in Medicare: small step or giant leap?

PMID- 24733200
TI  - Carbapenem-resistant Enterobacteriaceae: a call for cultural change.

PMID- 24733201
TI  - Diabetes, prediabetes, and glycemic control in the United States: challenges and
      opportunities.

PMID- 24733202
TI  - Delirium severity in the hospitalized patient: time to pay attention.

PMID- 24733203
TI  - The day the EHR died.

PMID- 24733204
TI  - Dancing on Thursdays.

PMID- 24733205
TI  - Corpulence and correspondence.

PMID- 24733206
TI  - Corpulence and correspondence.

PMID- 24733207
TI  - Triple therapy for hepatitis C virus infection in patients receiving
      hemodialysis.

PMID- 24733208
TI  - Triple therapy for hepatitis C virus infection in patients receiving
      hemodialysis.

PMID- 24733209
TI  - Links between herpes zoster incidence and childhood varicella vaccination.

PMID- 24733210
TI  - Links between herpes zoster incidence and childhood varicella vaccination.

PMID- 24733211
TI  - Texting while doctoring.

PMID- 24733212
TI  - Texting while doctoring.

PMID- 24733213
TI  - Texting while doctoring.

PMID- 24733214
TI  - Web Exclusives. The Consult Guys--blindness after surgery: can you see the
      answer?

PMID- 24733215
TI  - ACP Journal Club. In patients with obstructive sleep apnea and resistant
      hypertension, CPAP reduced 24-hour blood pressure.

PMID- 24733216
TI  - ACP Journal Club. Review: Cholinesterase inhibitors do not prevent dementia in
      patients with mild cognitive impairment.

PMID- 24733217
TI  - ACP Journal Club. Review: In neuropathy, fibromyalgia, or chronic pain,
      duloxetine reduces pain but increases adverse events.

PMID- 24733218
TI  - ACP Journal Club. Review: Calprotectin testing differentiates inflammatory bowel
      disease from the irritable bowel syndrome.

PMID- 24733219
TI  - ACP Journal Club. Review: Nicotine replacement therapy increases CVD events;
      bupropion and varenicline do not.

PMID- 24733220
TI  - ACP Journal Club. Review: Exercise reduces mortality compared with drugs in
      stroke but not in CHD, HF, or prediabetes.

PMID- 24733221
TI  - ACP Journal Club. Review: Exercise programs after pulmonary rehabilitation
      preserve short-term exercise capacity in COPD.

PMID- 24733222
TI  - ACP Journal Club. Review: Dabigatran does not differ from vitamin K antagonists
      for mortality or major bleeding.

PMID- 24733223
TI  - ACP Journal Club. 4F-PCC was noninferior to plasma in patients with acute major
      bleeding who needed urgent VKA reversal.

PMID- 24733224
TI  - ACP Journal Club. After a first proximal DVT, compression stockings did not
      prevent the postthrombotic syndrome.

PMID- 24733225
TI  - ACP Journal Club. Review: In stable obstructive CAD, PCI plus medical therapy
      (MT) does not differ from MT alone.

PMID- 24733226
TI  - ACP Journal Club. Review: CABG reduces long-term mortality and morbidity more
      than PCI in multivessel coronary disease.

PMID- 24733227
TI  - Physical activity: does environment make a difference for tension, stress,
      emotional outlook, and perceptions of health status?
AB  - BACKGROUND: The importance of physical activity for health is well-established.
      Questions remain whether outdoor exercise additionally benefits overall mental
      and physical well-being. METHODS: Using cross-sectional data from the Aerobics
      Center Longitudinal Study, we examined relationships of physical activity
      environment (PAE) with reported tension, stress, emotional outlook, and health.
      RESULTS: 11,649 participants were included. 18% exercised indoors, 54% outdoors,
      and 28% in both. Participants who exercised partially or entirely outdoors
      exercised more. In fully adjusted models, for women combined PAE was protective
      for worse emotional outlook (OR: 0.72; 95% CI: 0.52-0.98). Combined PAE was also
      protective for reported poor health (OR for women: 0.63; 95% CI: 0.44-0.91; OR
      for men: 0.75; 95% CI: 0.61-0.92). Amount of physical activity modified PAE
      relationships with outcomes. Combined and outdoor PAE were more consistently
      protective for worse outcomes among high activity participants. Regardless of
      PAE, better outcomes were observed in active versus inactive participants.
      CONCLUSION: The current study suggests addition of outdoor PAE may be linked with
      better stress management, outlook and health perceptions for more active
      populations, whereas indoor PAE may be more important for low active populations.
      Further research should examine the order of causation and whether type of
      outdoor PAE (eg, urban, natural) is important.

PMID- 24733228
TI  - Meaningful use and quality of care.

PMID- 24733229
TI  - Ileal mucormycosis: a rare cause of lower gastrointestinal bleeding.

PMID- 24733230
TI  - Moderating effects of nurses' organizational support on the relationship between
      job satisfaction and organizational commitment.
AB  - The aim was to investigate whether job satisfaction enhances organizational
      commitment among nursing personnel while exploring whether organizational support
      perception has a moderating effect on the relationship between their job
      satisfaction and organizational commitment. A cross-sectional survey was sent to
      400 nurses; 386 valid questionnaires were collected, with a valid response rate
      of 96.5%. According to the research findings, nurses' job satisfaction has a
      positive and significant influence on organizational commitment. Results also
      indicated that the moderating effect of nurses' organizational support perception
      on the relationship between their job satisfaction and organizational commitment
      was stronger for high organizational support perception than it was for low
      organizational support perception. This study suggests that organizational
      support perception will develop a sense of belonging, and this will help improve
      nurses' job satisfaction and organizational commitment. This kind of relationship
      is rarely discussed in the research literature, and it can be applied for human
      resources management of nursing staff. 

PMID- 24733231
TI  - Correlates of self-reported incarceration among homeless gay and bisexual
      stimulant-using young adults.
AB  - Gay and bisexual (G/B) homeless adults face multiple challenges in life which may
      place them at high risk for incarceration. Yet, little is known about this
      understudied population in terms of risk for incarceration. Baseline data
      collected from a longitudinal study between October 2009 and March 2012 in
      Hollywood, California, explored correlates of self-reported incarceration among
      G/B homeless stimulant-using adults (N = 353). Findings revealed older age, less
      education, having children, as well as a history of injection drug use and being
      born in the United States were positively associated with incarceration.
      Moreover, having poor social support and having received hepatitis information
      were also correlated with a history of incarceration. Our findings help us gain a
      greater awareness of homeless G/B adults who may be at greater risk for
      incarceration, which may be used by health care providers to design targeted
      interventions for this underserved population. 

PMID- 24733232
TI  - Factors Associated With Forensic Nurses Offering HIV nPEP Status Post Sexual
      Assault.
AB  - Nonoccupational, postexposure prophylaxis (nPEP) for human immunodeficiency virus
      (HIV) is offered inconsistently to patients who have been sexually assaulted.
      This may be due to Forensic Nurse Examiner (FNE) programs utilizing diverse nPEP
      protocols and HIV risk assessment algorithms. This study examines factors
      associated with FNEs offering nPEP to patients following sexual assault at two
      FNE programs in urban settings. Offering nPEP is mostly driven by site-specific
      protocol. At Site 1, in addition to open anal or open genital wounds, the
      presence of injury to the head or face was associated with FNEs offering nPEP
      (adjusted odds ratio [AOR] 64.15, 95% confidence interval [CI] = [2.12,
      1942.37]). At Site 2, patients assaulted by someone of Other race/ethnicity (non
      White, non-African American) were 86% less likely to be offered nPEP (AOR 0.14,
      95% CI = [.03, .72]) than patients assaulted by Whites. In addition to following
      site-specific protocols, future research should further explore the mechanisms
      influencing clinician decision making. 

PMID- 24733233
TI  - Motivational interviewing to improve diabetes outcomes in African Americans
      adults with diabetes.
AB  - The purpose of this study was to determine the effect of a motivational
      interviewing intervention (MII) on regimen adherence and diabetes markers among
      African Americans with diabetes. Sixty-two participants were assigned to the
      usual care (UC; n = 36) or MII (n = 26) groups. UC participants received the
      usual clinic care. MII participants received a maximum of six motivational
      interviewing (MI) sessions over 3 months. Outcome variables were obtained at
      baseline and 3-month follow-up. Data were obtained using medical records, self
      reports, and glucose monitor and accelerometer print-outs. MII significantly
      increased the odds of participants adhering to recommended physical activity
      level (66.7% vs. 38.8%, odds ratio = 2.92, 95% confidence interval = [1.6, 14.3],
      p = .018) and significantly decreased glucose levels (p = .043) and body mass
      index (p = .046) over time when compared with UC. Findings support using MI as an
      intervention for improving health outcomes and regimen adherence rates among the
      study population. 

PMID- 24733234
TI  - Cognitive function as measured by trail making test in patients with COPD.
AB  - People with chronic obstructive pulmonary disease (COPD) exhibit cognitive
      impairment in several subdomains, but little is known about factors associated
      with cognitive function and its relationship to health-related quality of life
      (HRQOL) in people with COPD. A data set from the National Emphysema Treatment
      Trial was used for this study. Data were obtained through questionnaires and
      clinical testing. Cognitive function in people with COPD was measured with the
      Trail Making Test. Descriptive and inferential statistics were used to analyze
      the data. Participants with COPD had slightly impaired processing speed and
      executive function. Test results revealed that age, gender, education, and income
      were significantly associated with cognitive function. Test scores also showed
      that cognitive function was significantly associated with HRQOL in people with
      COPD. This finding suggests that cognitive function should be screened in people
      with COPD. 

PMID- 24733235
TI  - Varenicline, low dose naltrexone, and their combination for heavy-drinking
      smokers: human laboratory findings.
AB  - RATIONALE: Heavy-drinking smokers constitute a sizeable and hard-to-treat
      subgroup of smokers, for whom tailored smoking cessation therapies are not yet
      available. OBJECTIVES: The present study used a double-blind, randomized, 2 * 2
      medication design, testing varenicline alone (VAR; 1 mg twice daily), low dose
      naltrexone alone (L-NTX; 25 mg once daily), varenicline plus naltrexone, and
      placebo for effects on cigarette craving and subjective response to alcohol and
      cigarettes in a sample (n = 130) of heavy-drinking daily smokers (>=10
      cigarettes/day). METHODS: All participants were tested after a 9-day titration
      period designed to reach a steady state on the target medication. Testing was
      completed at 12 h of nicotine abstinence, after consuming a standard dose of
      alcohol (target breath alcohol concentration = 0.06 g/dl) and after smoking the
      first cigarette of the day. RESULTS: The combination of VAR + L-NTX was superior
      to placebo, and at times superior to monotherapy, in attenuating cigarette
      craving, cigarette and alcohol "high," and in reducing ad-lib consumption of both
      cigarettes and alcohol during the 9-day medication titration period. CONCLUSIONS:
      These preliminary findings indicate that clinical studies of the combination of
      VAR + L-NTX for heavy drinkers trying to quit smoking are warranted and may
      ultimately improve clinical care for this sizeable and treatment-resistant
      subgroup of smokers.

PMID- 24733236
TI  - Phosphorylation of hypothalamic AMPK on serine(485/491) related to sustained
      weight loss by alpha-lipoic acid in mice treated with olanzapine.
AB  - RATIONALE: Alpha-lipoic acid (ALA) was shown to suppress atypical antipsychotic
      drug (AAPD)-induced weight gain. However, its mode of action has remained
      unidentified. OBJECTIVE: We aimed to identify mechanisms underlying anti-obesity
      effects of ALA in mice treated with olanzapine. METHODS: We compared body weight
      and food intake among vehicle-, olanzapine-, and olanzapine plus ALA-treated
      mice, and measured hypothalamic AMP-activated protein kinase (AMPK) activity by
      detecting levels of Thr(172) and Ser(485/491) phosphorylation, which indicate
      activation and inhibition of AMPK, respectively. RESULTS: Body weights were
      increased by olanzapine in parallel with increased levels of Thr(172)
      phosphorylation of hypothalamic AMPK. Initially increased rate of weight gain was
      diminished as Thr(172) phosphorylation levels were decreased to control levels
      after 10 days of olanzapine treatment. ALA successfully not only prevented
      olanzapine-induced weight gain but also induced additional weight loss even
      relative to control levels throughout the treatment period. During the initial
      stage, ALA's action was indicated by both suppression of olanzapine-induced
      Thr(172) phosphorylation and an increase in Ser(485/491) phosphorylation levels.
      However, in the later stage when no more increases in Thr(172) phosphorylation
      and weight gain by olanzapine were observed, ALA's action was only indicated by
      increased levels of Ser(485/491) phosphorylation. CONCLUSIONS: Our data suggest
      that anti-obesity effects of ALA may be related to modulation of both
      Ser(485/491) phosphorylation and Thr(172) phosphorylation of hypothalamic AMPK,
      while olanzapine-induced weight gain may be only associated with increase in
      Thr(172) phosphorylation. This might be an important mechanistic clue for the
      future development of anti-obesity drugs beyond control of AAPD-induced weight
      gain.

PMID- 24733238
TI  - Recombineering: genetic engineering in bacteria using homologous recombination.
AB  - The bacterial chromosome and bacterial plasmids can be engineered in vivo by
      homologous recombination using PCR products and synthetic oligonucleotides as
      substrates. This is possible because bacteriophage-encoded recombination proteins
      efficiently recombine sequences with homologies as short as 35 to 50 bases.
      Recombineering allows DNA sequences to be inserted or deleted without regard to
      location of restriction sites. This unit first describes preparation of
      electrocompetent cells expressing the recombineering functions and their
      transformation with dsDNA or ssDNA. It then presents support protocols that
      describe several two-step selection/counter-selection methods of making genetic
      alterations without leaving any unwanted changes in the targeted DNA, and a
      method for retrieving onto a plasmid a genetic marker (cloning by retrieval) from
      the Escherichia coli chromosome or a co-electroporated DNA fragment. Additional
      protocols describe methods to screen for unselected mutations, removal of the
      defective prophage from recombineering strains, and other useful techniques.

PMID- 24733237
TI  - Altered cerebellar and prefrontal cortex function in rhesus monkeys that
      previously self-administered cocaine.
AB  - RATIONALE: Differences in brain function in cocaine users can occur even when
      frank deficits are not apparent, indicating neuroadaptive consequences of use.
      Using monkeys to investigate altered metabolic activity following chronic cocaine
      self-administration allows an assessment of altered function due to cocaine use,
      without confounding pre-existing differences or polysubstance use often present
      in clinical studies. OBJECTIVES: To evaluate alterations in metabolic function
      during a working memory task in the prefrontal cortex and the cerebellum
      following 1 year of chronic cocaine self-administration followed by a 20 month
      drug-free period. METHODS: Fluorodeoxyglucose ((18)F) PET imaging was used to
      evaluate changes in relative regional metabolic activity associated with a
      delayed match to sample working memory task. Chronic cocaine animals were
      compared to a control group, and region of interest analyses focused on the
      dorsolateral prefrontal cortex (DLPFC) and cerebellum. RESULTS: Despite no
      differences in task performance, in the cocaine group, the cerebellum showed
      greater metabolic activity during the working memory task (relative to the
      control task) compared to the control group. There was also a trend toward a
      significant difference between the groups in DLPFC activity (p = 0.054), with the
      cocaine group exhibiting lower DLPFC metabolic activity during the delay task
      (relative to the control task) than the control group. CONCLUSION: The results
      support clinical indications of increased cerebellar activity associated with
      chronic cocaine exposure. Consistent with evidence of functional interactions
      between cerebellum and prefrontal cortex, these changes may serve to compensate
      for potential impairments in functionality of DLPFC.

PMID- 24733239
TI  - Informatics for molecular biologists.

PMID- 24733240
TI  - Detection of Mycoplasma contamination in cell cultures.
AB  - Mycoplasma contamination of cell lines is a major problem in cell culture
      technology. This unit presents protocols involving either the polymerase chain
      reaction (PCR) or fluorescent in situ hybridization (FISH) to provide
      independent, fast, and sensitive techniques to monitor mycoplasma contamination
      in laboratory cultures. Special emphasis is placed on the integration of control
      reactions to prevent false-negative as well as false-positive results due to
      reaction inhibition or contamination and background staining, respectively.

PMID- 24733241
TI  - Eradication of Mycoplasma contaminations from cell cultures.
AB  - Mycoplasma contaminations have a multitude of effects on cultured cell lines that
      may influence the results of experiments or pollute bioactive substances isolated
      from the eukaryotic cells. The elimination of mycoplasma contaminations from cell
      cultures with antibiotics has been proven to be a practical alternative to
      discarding and re-establishing important or irreplaceable cell lines. Different
      fluoroquinolones, tetracyclins, pleuromutilins, and macrolides shown to have
      strong anti-mycoplasma properties are employed for the decontamination. These
      antibiotics are applied as single treatments, as combination treatment of two
      antibiotics in parallel or successively, or in combination with a surface-active
      peptide to enhance the action of the antibiotic. The protocols in this unit allow
      eradication of mycoplasmas, prevention of the development of resistant mycoplasma
      strains, and potential cure of heavily contaminated and damaged cells. Consistent
      and permanent alterations to eukaryotic cells attributable to the treatment have
      not been demonstrated.

PMID- 24733242
TI  - Next-Generation Sequencing RNA-Seq Library Construction.
AB  - This unit presents protocols for construction of next-generation sequencing (NGS)
      directional RNA sequencing libraries for the Illumina HiSeq and MiSeq from a wide
      variety of input RNA sources. The protocols are based on the New England Biolabs
      (NEB) small RNA library preparation set for Illumina, although similar kits exist
      from different vendors. The protocol preserves the orientation of the original
      RNA in the final sequencing library, enabling strand-specific analysis of the
      resulting data. These libraries have been used for differential gene expression
      analysis and small RNA discovery and are currently being tested for de novo
      transcriptome assembly. The protocol is robust and applicable to a broad range of
      RNA input types and RNA quality, making it ideal for high-throughput
      laboratories.

PMID- 24733244
TI  - Deletion in the EVC2 gene causes chondrodysplastic dwarfism in Tyrolean Grey
      cattle.
AB  - During the summer of 2013 seven Italian Tyrolean Grey calves were born with
      abnormally short limbs. Detailed clinical and pathological examination revealed
      similarities to chondrodysplastic dwarfism. Pedigree analysis showed a common
      founder, assuming autosomal monogenic recessive transmission of the defective
      allele. A positional cloning approach combining genome wide association and
      homozygosity mapping identified a single 1.6 Mb genomic region on BTA 6 that was
      associated with the disease. Whole genome re-sequencing of an affected calf
      revealed a single candidate causal mutation in the Ellis van Creveld syndrome 2
      (EVC2) gene. This gene is known to be associated with chondrodysplastic dwarfism
      in Japanese Brown cattle, and dwarfism, abnormal nails and teeth, and dysostosis
      in humans with Ellis-van Creveld syndrome. Sanger sequencing confirmed the
      presence of a 2 bp deletion in exon 19 (c.2993_2994ACdel) that led to a premature
      stop codon in the coding sequence of bovine EVC2, and was concordant with the
      recessive pattern of inheritance in affected and carrier animals. This loss of
      function mutation confirms the important role of EVC2 in bone development.
      Genetic testing can now be used to eliminate this form of chondrodysplastic
      dwarfism from Tyrolean Grey cattle. 

PMID- 24733243
TI  - Genome-Wide Fitness and Genetic Interactions Determined by Tn-seq, a High
      Throughput Massively Parallel Sequencing Method for Microorganisms.
AB  - The lagging annotation of bacterial genomes and the inherent genetic complexity
      of many phenotypes is hindering the discovery of new drug targets and the
      development of new antimicrobial agents and vaccines. This unit presents Tn-seq,
      a method that has made it possible to quantitatively determine fitness for most
      genes in a microorganism and to screen for quantitative genetic interactions on a
      genome-wide scale and in a high-throughput fashion. Tn-seq can thus direct
      studies on the annotation of genes and untangle complex phenotypes. The method is
      based on the construction of a saturated transposon insertion library. After
      library selection, changes in the frequency of each insertion mutant are
      determined by sequencing flanking regions en masse. These changes are used to
      calculate each mutant's fitness. The method was originally developed for the Gram
      positive bacterium Streptococcus pneumoniae, a causative agent of pneumonia and
      meningitis, but has now been applied to several different microbial species.

PMID- 24733245
TI  - Plasma and cerebrospinal fluid concentrations of ibuprofen in pediatric patients
      and antipyretic effect: Pharmacokinetic-pharmacodynamic modeling analysis.
AB  - We aimed to determine the relationship between plasma and cerebrospinal fluid
      (CSF) concentrations of ibuprofen and the antipyretic effect in pediatric
      patients. A prospective cohort of infants and children aged 3 months to 15 years
      and treated with ibuprofen was studied. The patients received ibuprofen (via oral
      route, median dose of 10.0 mg/kg; 3.4-11.4 mg/kg range), samples of blood and CSF
      were collected, and body temperature was measured. Sequential analysis of the
      pharmacokinetic and pharmacodynamic data from 28 patients was performed using a
      population modeling approach. The observed concentration versus time data
      indicated substantial pharmacokinetic variability in absorption and distribution
      of ibuprofen between the patients. The pharmacokinetic modeling outcomes indicate
      that following a ~25-minute lag time, ibuprofen is rapidly absorbed to the
      central compartment and rapidly equilibrates with the CSF, resulting in the total
      ibuprofen concentration in the CSF versus plasma (CCSF /Cplasma ) of 0.011 +/-
      0.007. The antipyretic effect of ibuprofen was best described by an indirect
      response PK-PD model incorporating patient baseline body temperature and
      ibuprofen concentration in the CSF. We conclude that the pharmacokinetic
      pharmacodynamic modeling can be used to predict the time course of ibuprofen
      plasma and CSF concentrations and of the antipyretic effects in individual
      pediatric patients. 

PMID- 24733246
TI  - Persistent inequalities in child undernutrition: evidence from 80 countries, from
      1990 to today.
AB  - BACKGROUND: Global progress in reducing the burden of undernutrition tends to be
      measured at the population level. It has been hypothesized that population-level
      improvements may mask widening socioeconomic inequalities, but little attempt has
      been made to assess whether this is true. METHODS: Original data from 131
      demographic health surveys and 48 multiple indicator cluster surveys from 1990 to
      2011 were used to examine trends in socioeconomic inequalities in stunting and
      underweight, as well as the relationship between changes in prevalence and
      changes in inequality, in 80 countries. Socioeconomic inequality is measured
      using the corrected concentration index. RESULTS: Countries with a higher
      prevalence of stunting tend to have larger socioeconomic inequalities in stunting
      (Spearman rank correlation = -0.27 P = 0.014). In most countries, there has been
      no change in inequality in stunting: in 31 out of 53, the 90% confidence
      intervals around the changes overlap the zero value. In the remaining 22, there
      was a reduction in inequality in 11 and an increase in 11. The distributional
      patterns underlying the summary inequality statistics vary considerably across
      countries, but in most there have been considerable gains to the poorest
      quintile. CONCLUSIONS: Reductions in the prevalence of undernutrition have
      generally not been accompanied by widening inequalities. However, inequalities
      have also not been narrowing. Rather, the picture is one of a strong persistence
      of existing inequalities. In addition, there are different distributional
      patterns underlying changes in the summary indices of inequality which will need
      to be taken into consideration in designing programmes to reach the poor.

PMID- 24733247
TI  - Weight status in young adulthood and survival after cardiovascular diseases and
      cancer.
AB  - BACKGROUND: Some studies have suggested that overweight is associated with lower
      mortality, but these results may be affected by reverse causality. We analysed
      how body mass index (BMI) in young adulthood is associated with mortality in the
      general population and after the diagnoses of coronary heart disease (CHD),
      stroke and cancer. METHODS: BMI was measured at an average age of 18 years in 734
      438 Swedish men born in 1950-65. Diagnoses of CHD, stroke and cancer as well as
      all-cause mortality were derived from registers covering the whole population, up
      to 31 December 2010. The follow-up of 24.56 million person-years included 33 067
      cases of mortality and 19 843 CHD, 13 578 stroke and 27 365 cancer diagnoses.
      Hazard ratios (HR) [with 95% confidence intervals (CI)] were estimated by the Cox
      proportional hazards model. RESULTS: Higher mortality in the whole cohort (HR =
      1.26, 1.21-1.32) as well as after the diagnosis of CHD (HR = 1.33, 1.09-1.63) or
      cancer (HR = 1.13, 1.01-1.25) was found in moderately overweight men (BMI 25.0
      27.4 kg/m(2)) as compared with normal weight men (BMI 20.1-22.4 kg/m(2)); for
      stroke patients the result for the same BMI categories was not statistically
      significant (HR = 1.17, 0.94-1.45). Mortality increased with increasing weight
      status and was highest in obese men (BMI >30 kg/m(2)): HR = 2.17 (2.02-2.34) for
      the whole cohort, 2.35 (1.81-3.05) after the diagnosis of CHD, 2.08 (1.56-2.77)
      after stroke and 1.68 (1.40-2.01) after cancer. CONCLUSIONS: Even moderate
      overweight in young adulthood increases all-cause mortality and mortality after
      the diagnosis of CHD, stroke and cancer in men. Preventing overweight in young
      adulthood remains as an important public health issue.

PMID- 24733248
TI  - Potential of Start Codon Targeted (SCoT) markers for DNA fingerprinting of newly
      synthesized tritordeums and their respective parents.
AB  - Hexaploid tritordeum (H(ch)H(ch)AABB; 2n = 42) results from the cross between
      Hordeum chilense (H(ch)H(ch); 2n = 14) and cultivated durum wheat (Triticum
      turgidum ssp. durum (AABB; 2n = 28). Morphologically, tritordeum resembles the
      wheat parent, showing promise for agriculture and wheat breeding. Start Codon
      Targeted (SCoT) polymorphism is a recently developed technique that generates
      gene-targeted markers. Thus, we considered it interesting to evaluate its
      potential for the DNA fingerprinting of newly synthesized hexaploid tritordeums
      and their respective parents. In this study, 60 SCoT primers were tested, and 18
      and 19 of them revealed SCoT polymorphisms in the newly synthesized tritordeum
      lines HT27 and HT22, respectively, and their parents. An analysis of the
      presence/absence of bands among tritordeums and their parents revealed three
      types of polymorphic markers: (i) shared by tritordeums and one of their parents,
      (ii) exclusively amplified in tritordeums, and (iii) exclusively amplified in the
      parents. No polymorphism was detected among individuals of each parental species.
      Three SCoT markers were exclusively amplified in tritordeums of lines HT22 and
      HT27, being considered as polyploidization-induced rearrangements. About 70% of
      the SCoT markers of H. chilense origin were not transmitted to the allopolyploids
      of both lines, and most of the SCoTs scored in the newly synthesized
      allopolyploids originated from wheat, reinforcing the potential use of tritordeum
      as an alternative crop.

PMID- 24733249
TI  - Paradoxical mucocutaneous flare in a case of Behcet's disease treated with
      tocilizumab.
AB  - We report on a patient with a long-standing history of recurrent oral aphthosis
      and pseudofolliculitis, diagnosed with Behcet's disease (BD), previously treated
      with high-dose prednisone, colchicine, cyclosporine, cyclophosphamide and
      methotrexate, all of which were partially effective. Treatment with the chimeric
      mouse-human anti-tumour necrosis factor (TNF)-alpha monoclonal antibody
      infliximab brought about the resolution of mucocutaneous lesions for a period of
      6 years. After an oral and articular BD relapse, the anti-interleukin-6 agent
      tocilizumab was started in association with high-dose prednisone. Unexpectedly,
      the patient experienced a paradoxical mucocutaneous flare following tocilizumab
      administration, which worsened after the second infusion. Tocilizumab was then
      discontinued, and total recovery was achieved after the patient was started on
      the fully human anti-TNF-alpha monoclonal antibody golimumab in association with
      colchicine and methylprednisolone.

PMID- 24733251
TI  - Anakinra treatment in patients with gout and type 2 diabetes.
AB  - We report three Caucasian patients affected by gout and type 2 diabetes, who were
      treated with the recombinant nonglycosylated human interleukin-1 receptor
      antagonist anakinra (100 mg/day subcutaneously) after an unsatisfactory or
      incomplete response to urate-lowering therapy, colchicine, nonsteroidal anti
      inflammatory drugs, and prednisone. The remarkable clinical improvement in joint
      symptoms within 24 h and in glycemic control during a 6-month period gives
      anakinra a potential therapeutic role in the management of gout and type 2
      diabetes. When anakinra was discontinued, a gout attack occurred within 3-25 days
      in all three patients. The contribution of anakinra in the treatment of such
      syndromes is encouraging, but requires further studies to establish its long-term
      efficacy.

PMID- 24733250
TI  - Inhibition of transient receptor potential melastatin 7 (TRPM7) channel induces
      RA FLSs apoptosis through endoplasmic reticulum (ER) stress.
AB  - Transient receptor potential melastatin 7 (TRPM7) is involved in both normal
      physiological processes and pathology of various diseases. The purpose of this
      study was to explore the function and underlying mechanisms of TRPM7 channels in
      rheumatoid arthritis (RA) fibroblast-like synoviocytes (FLSs) apoptosis induced
      by thapsigargin in vitro. In this study, using a combination of Western blotting,
      RT-PCR, and nuclear morphology analysis, we investigated the influence and
      potential function of TRPM7 channels on the apoptosis induced by thapsigargin in
      RA FLSs. Chemical inhibitors (Gd(3+) and 2-APB) and specific siRNA for TRPM7 were
      used to study the role of TRPM7 in RA FLSs apoptosis. The expression of TRPM7 was
      significantly potentiated in RA FLSs. Co-incubation of RA FLSs with Gd(3+), 2
      APB, or TRPM7-siRNA increased cell apoptosis. Furthermore, we found that
      suppression of TRPM7 channels also increased the expression CHOP and calpain and
      decreased the expression caspase-3. We conclude that suppression of TRPM7
      channels may increase RA FLSs apoptosis in vitro, and this is associated with
      endoplasmic reticulum (ER) stress. Therefore, inhibition of TRPM7 could activate
      ER stress and induce RA FLSs apoptosis. 

PMID- 24733252
TI  - The apoptosis of osteoblasts and osteocytes in femoral head osteonecrosis: its
      specificity and its distribution.
AB  - The pathogenesis of nontraumatic osteonecrosis (ON) remains unclear. Some studies
      have suggested that nontraumatic ON is attributed to increased osteocytic
      apoptosis. To test this hypothesis, a controlled study must compare the apoptosis
      of osteocytes and osteoblasts in cases of ON and osteoarthritis (OA). To assess
      either the localized or diffuse patterns of this increased osteocytic and
      osteoblastic apoptosis, we evaluated both the proximal and distal regions of
      necrotic areas. Femoral heads resected for total hip prosthesis were included for
      this study. Of these, 10 were ON cases-three were induced by corticosteroids,
      three by alcohol abuse, one resulted from trauma, one resulted from hyperlipemia,
      and two were idiopathic-10 were osteoarthritis cases, and 1 from a patient
      suffering from a subcapital fracture. The TUNEL reaction was used to detect the
      apoptosis in osteoblasts and osteocytes. A semi-quantitative evaluation was
      conducted, at both distal and proximal areas relative to the lesions,
      specifically in the area surrounding the necrotic region in the osteonecrosis
      cases, in the eburnated bone in the osteoarthritis cases, and in the subchondral
      bone fracture. The apoptosis of osteoblasts and osteocytes was statistically more
      frequent in the regions close to the necrotic areas in the ON group. No
      difference was found in the unpaired areas. In the ON group, no difference was
      found in terms of the etiological factors. During ON, the apoptosis of osteocytes
      and osteoblasts is increased proximally to the necrotic regions in the patients
      presenting with osteoarthritis and subcapital fractures. This increase was found
      not only in the corticosteroid-induced ON cases but also in the idiopathic and
      alcohol abuse- and trauma-induced ON cases.

PMID- 24733254
TI  - Convergent routes to substituted naphthylamides.
AB  - Practical, convergent routes to variously substituted 1- and 2-naphthylamides
      have been developed. They exploit the ability of xanthates to undergo both
      intermolecular radical additions to vinyl pivalate and intramolecular radical
      cyclisations to aromatic rings. In the case of 1-naphthylamides, the existence of
      an intramolecular hydrogen bond was used to facilitate the cyclisation step. 

PMID- 24733253
TI  - Multicentric reticulohistiocytosis: case report with response to infliximab and
      review of treatment options.
AB  - Multicentric reticulohistiocytosis (MRH) is a rare systemic and devastating
      disease with main involvement of skin and joints, frequently related with
      malignancies. Macrophages and TNFalpha are the main targets of multiple treatment
      options with variable results. Although MRH has the tendency of self-resolve in
      an average of 8 years, treatment must be started early to avoid sequelae, mainly
      in joints with severe deformities and daily life activity impairment. We describe
      a 50-year-old man with skin and joint involvement, with a non-previously
      described muscle affectation, that failed to different drugs and achieved skin
      improvement with infliximab. We review for the first time in medical literature
      the available therapeutic options of MRH and its outcomes and propose possible
      future targets.

PMID- 24733255
TI  - Completely ES cell-derived mice produced by tetraploid complementation using
      inner cell mass (ICM) deficient blastocysts.
AB  - Tetraploid complementation is often used to produce mice from embryonic stem
      cells (ESCs) by injection of diploid (2n) ESCs into tetraploid (4n) blastocysts
      (ESC-derived mice). This method has also been adapted to mouse cloning and the
      derivation of mice from induced pluripotent stem (iPS) cells. However, the
      underlying mechanism(s) of the tetraploid complementation remains largely
      unclear. Whether this approach can give rise to completely ES cell-derived mice
      is an open question, and has not yet been unambiguously proven. Here, we show
      that mouse tetraploid blastocysts can be classified into two groups, according to
      the presence or absence of an inner cell mass (ICM). We designate these as type a
      (presence of ICM at blastocyst stage) or type b (absence of ICM). ESC lines were
      readily derived from type a blastocysts, suggesting that these embryos retain a
      pluripotent epiblast compartment; whereas the type b blastocysts possessed very
      low potential to give rise to ESC lines, suggesting that they had lost the
      pluripotent epiblast. When the type a blastocysts were used for tetraploid
      complementation, some of the resulting mice were found to be 2n/4n chimeric;
      whereas when type b blastocysts were used as hosts, the resulting mice are all
      completely ES cell-derived, with the newborn pups displaying a high frequency of
      abdominal hernias. Our results demonstrate that completely ES cell-derived mice
      can be produced using ICM-deficient 4n blastocysts, and provide evidence that the
      exclusion of tetraploid cells from the fetus in 2n/4n chimeras can largely be
      attributed to the formation of ICM-deficient blastocysts. 

PMID- 24733256
TI  - Conventional versus laparoscopic surgery for hepatic hydatidosis: a 6-year single
      center experience.
AB  - BACKGROUND: The aim of this study is to evaluate the clinical results of
      laparoscopic surgery compared with conventional surgery. METHODS: Records of
      patients who underwent surgery for liver hydatid disease between 2005 and 2011
      were reviewed. Operative time, blood loss, conversion to open, postoperative
      morbidity, mortality, hospital stay, and recurrence rate were measured. RESULTS:
      Among 353 eligible patients, 60 were considered for laparoscopic and 293 for
      conventional surgery. Operative time was slightly increased in laparoscopic
      group. No major blood loss and blood transfusion were needed. Postoperative
      hospital stay was significantly short in laparoscopic group (3.8 +/- 1.2 days)
      than that in conventional group (7.4 +/- 1.4 days). The overall morbidity was
      13.3 % (8/60) in laparoscopic and 19.8 % (58/293) in conventional group without
      significance. Both conversion rate and mortality was 0 %. One recurrence in
      laparoscopic (1.7 %, 1/60) and five in conventional group (1.7 %, 5/293) occurred
      within 48 months of follow-up. CONCLUSIONS: Laparoscopic treatment of liver
      hydatid disease is safe and effective in selected patients with all its
      advantages.

PMID- 24733257
TI  - Volume-outcome associations after major hepatectomy for hepatocellular carcinoma:
      a nationwide Taiwan study.
AB  - OBJECTIVE: The objective of this study was to explore volume-outcome associations
      after major hepatectomy for hepatocellular carcinoma (HCC). METHODS: This
      population-based cohort study retrospectively analyzed 23,107 major hepatectomies
      for HCC patients from 1998 to 2009. Relationships between hospital/surgeon volume
      and patient outcome were analyzed by propensity score matching (PSM). Five-year
      overall survival (OS) was estimated by Kaplan-Meier method, and differences were
      compared by log-rank test. RESULTS: The mean length of stay (LOS) after major
      hepatectomy was 18.1 days, and the mean hospital cost was US$5,088.2. After PSM,
      the mean OS in high- and low-volume hospitals was 71.1 months (standard deviation
      (SD) 0.7 months) and 68.6 months (SD 0.6 months), respectively; the mean OS in
      high- and low-volume surgeons was 78.5 months (SD 0.7 months) and 66.9 months (SD
      0.7 months), respectively. The PSM analysis showed that treatment by high-volume
      hospitals and treatment by high-volume surgeons were both associated with
      significantly shorter LOS, lower hospital cost, and longer survival compared to
      their low-volume counterparts (P < 0.001). CONCLUSIONS: The results of this
      nationwide study support the regionalization of HCC treatment by hospital volume
      and by surgeon volume. High surgeon volume revealed both short- and long-term
      benefits. The applicability of PSM in volume-outcome analysis may also be
      confirmed.

PMID- 24733258
TI  - Discrete improvement in racial disparity in survival among patients with stage IV
      colorectal cancer: a 21-year population-based analysis.
AB  - PURPOSE: Recently, multiple clinical trials have demonstrated improved outcomes
      in patients with metastatic colorectal cancer. This study investigated if the
      improved survival is race dependent. PATIENTS AND METHODS: Overall and cancer
      specific survival of 77,490 White and Black patients with metastatic colorectal
      cancer from the 1988-2008 Surveillance Epidemiology and End Results registry were
      compared using unadjusted and multivariable adjusted Cox proportional hazard
      regression as well as competing risk analyses. RESULTS: Median age was 69 years,
      47.4 % were female and 86.0 % White. Median survival was 11 months overall, with
      an overall increase from 8 to 14 months between 1988 and 2008. Overall survival
      increased from 8 to 14 months for White, and from 6 to 13 months for Black
      patients. After multivariable adjustment, the following parameters were
      associated with better survival: White, female, younger, better educated and
      married patients, patients with higher income and living in urban areas, patients
      with rectosigmoid junction and rectal cancer, undergoing cancer-directed surgery,
      having well/moderately differentiated, and N0 tumors (p < 0.05 for all
      covariates). Discrepancies in overall survival based on race did not change
      significantly over time; however, there was a significant decrease of cancer
      specific survival discrepancies over time between White and Black patients with a
      hazard ratio of 0.995 (95 % confidence interval 0.991-1.000) per year (p = 0.03).
      CONCLUSION: A clinically relevant overall survival increase was found from 1988
      to 2008 in this population-based analysis for both White and Black patients with
      metastatic colorectal cancer. Although both White and Black patients benefitted
      from this improvement, a slight discrepancy between the two groups remained.

PMID- 24733259
TI  - Modified Blumgart anastomosis for pancreaticojejunostomy: technical improvement
      in matched historical control study.
AB  - BACKGROUND: Postoperative pancreatic fistula (POPF) is the main cause of fatal
      complications after pancreatoduodenectomy. There is still no universally accepted
      technique for pancreaticoenterostomy, especially in patients with soft pancreas.
      METHODS: Between July 2008 and June 2013, 240 patients who underwent
      pancreatoduodenectomy were enrolled in this single-institution matched historical
      control study. To approximate the pancreatic parenchyma to the jejunal
      seromuscular layer, 120 patients underwent anastomosis using the Kakita method
      (three or four interrupted penetrating sutures) and 120 underwent anastomosis
      using the modified Blumgart anastomosis (m-BA) method (one to three
      transpancreatic/jejunal seromuscular sutures to completely cover the pancreatic
      stump with jejunal serosa). RESULTS: The rate of clinically relevant POPF
      formation was significantly lower in the m-BA group than that in the Kakita group
      (2.5 vs 36 %; p < 0.001). The duration of drain placement and the length of
      postoperative hospital stay were significantly shorter in the m-BA group.
      Multivariate analysis showed that m-BA was an independent predictor of non
      formation of POPF (hazard ratio, 0.02; 95 % confidence interval, 0.01-0.08; p <
      0.001). CONCLUSION: The m-BA method is safe and simple and improves postoperative
      outcomes. We suggest that the m-BA is suitable for use as a standard method of
      pancreaticojejunostomy after pancreatoduodenectomy.

PMID- 24733260
TI  - Detection and molecular characterization of J subgroup avian leukosis virus in
      wild ducks in China.
AB  - To assess the status of avian leukosis virus subgroup J (ALV-J) in wild ducks in
      China, we examined samples from 528 wild ducks, representing 17 species, which
      were collected in China over the past 3 years. Virus isolation and PCR showed
      that 7 ALV-J strains were isolated from wild ducks. The env genes and the 3'UTRs
      from these isolates were cloned and sequenced. The env genes of all 7 wild duck
      isolates were significantly different from those in the prototype strain HPRS
      103, American strains, broiler ALV-J isolates and Chinese local chicken isolates,
      but showed close homology with those found in some layer chicken ALV-J isolates
      and belonged to the same group. The 3'UTRs of 7 ALV-J wild ducks isolates showed
      close homology with the prototype strain HPRS-103 and no obvious deletion was
      found in the 3'UTR except for a 1 bp deletion in the E element that introduced a
      binding site for c-Ets-1. Our study demonstrated the presence of ALV-J in wild
      ducks and investigated the molecular characterization of ALV-J in wild ducks
      isolates. 

PMID- 24733262
TI  - Low temperature growth of graphene on Cu-Ni alloy nanofibers for stable, flexible
      electrodes.
AB  - Here, we report a facile approach to grow graphene on Cu-Ni alloy NFs at a
      temperature as low as 450-500  degrees C, in which solid polystyrene (PS) carbon
      source and two-temperature-zone furnace were used to prepare graphene. The
      graphene coated Cu-Ni (designated as G-coated Cu-Ni) NFs were fully characterized
      by Raman spectra, XPS, FESEM and TEM. The G-coated Cu-Ni NFs exhibited excellent
      anti-oxidation, anti-corrosion and flexibility properties. The anti-corrosion of
      G-coated Cu-Ni NFs was examined through cyclic voltammetry measurements by using
      sea water as the electrolyte solution. Finally, using crossed arrays of G-coated
      Cu-Ni NF composite electrode thin films (sheet resistance is ~10 Omega sq(-1)) as
      the flexible electrode, an alternating current (AC) electroluminescent (EL)
      device with a configuration of G-coated Cu-Ni/active layer (ZnS : Cu
      phosphor)/dielectric layer (BaTiO3)/front electrode (CNT) has been fabricated.
      Under an AC voltage of 200 V and frequency of 1300 Hz, the ACEL device emitted
      blue light at 496 nm with a brightness of 103 cd m(-2). 

PMID- 24733263
TI  - Application of polypyrrole multi-walled carbon nanotube composite layer for
      detection of mercury, lead and iron ions using surface plasmon resonance
      technique.
AB  - Polypyrrole multi-walled carbon nanotube composite layers were used to modify the
      gold layer to measure heavy metal ions using the surface plasmon resonance
      technique. The new sensor was fabricated to detect trace amounts of mercury (Hg),
      lead (Pb), and iron (Fe) ions. In the present research, the sensitivity of a
      polypyrrole multi-walled carbon nanotube composite layer and a polypyrrole layer
      were compared. The application of polypyrrole multi-walled carbon nanotubes
      enhanced the sensitivity and accuracy of the sensor for detecting ions in an
      aqueous solution due to the binding of mercury, lead, and iron ions to the
      sensing layer. The Hg ion bonded to the sensing layer more strongly than did the
      Pb and Fe ions. The limitation of the sensor was calculated to be about 0.1 ppm,
      which produced an angle shift in the region of 0.3 degrees  to 0.6 degrees . 

PMID- 24733266
TI  - Paraneoplastic neuromyelitis optica spectrum disorder associated with metastatic
      carcinoid expressing aquaporin-4.
AB  - IMPORTANCE: Reports of neuromyelitis optica spectrum disorder (NMOSD) occurring
      in the setting of neoplasia suggest that aquaporin-4 autoimmunity may in some
      cases have a paraneoplastic basis. OBSERVATIONS: In this case report, we describe
      a patient with NMOSD whose test results were seropositive for aquaporin-4 IgG and
      who had a hepatic metastasis from a small-bowel neuroendocrine tumor. The tumor
      cells expressed aquaporin-4 immunoreactivity. She presented to the Neurology
      Department at Wayne State University with bilateral leg weakness, ascending
      paresthesias, and decreased sensation. CONCLUSIONS AND RELEVANCE: This case
      extends the context of NMOSD as a paraneoplastic disorder.

PMID- 24733267
TI  - Neuronal antibodies in Creutzfeldt-Jakob disease.

PMID- 24733268
TI  - Neuronal antibodies in Creutzfeldt-Jakob disease - reply.

PMID- 24733270
TI  - In memoriam: Theodore Leon Munsat, MD (1930-2013).

PMID- 24733271
TI  - Intraindividual variability of boldness is repeatable across contexts in a wild
      lizard.
AB  - Animals do not behave in exactly the same way when repeatedly tested in the same
      context or situation, even once systematic variation, such as habituation, has
      been controlled for. This unpredictability is called intraindividual variability
      (IIV) and has been little studied in animals. Here we investigated how IIV in
      boldness (estimated by flight initiation distances) changed across two seasons-
      the dry, non-breeding season and the wet, breeding season--in a wild population
      of the Namibian rock agama, Agama planiceps. We found significant differences in
      IIV both between individuals and seasons, and IIV was higher in the wet season,
      suggesting plasticity in IIV. Further, IIV was highly repeatable (r = 0.61)
      between seasons and we found strong negative correlations between consistent
      individual differences in flight initiation distances, i.e. their boldness, and
      individuals' IIVs. We suggest that to understand personality in animals,
      researchers should generate a personality 'profile' that includes not only the
      relative level of a trait (i.e. its personality), but also its plasticity and
      variability under natural conditions.

PMID- 24733272
TI  - Self-efficacy, action control, and social support explain physical activity
      changes among Costa Rican older adults.
AB  - BACKGROUND: Self-efficacy, action control, and social support are considered to
      influence changes in physical activity levels in older adults. This study
      examines the relationship among these variables and explores the putative
      mediating and moderating mechanisms that might account for activity changes.
      METHODS: A longitudinal study with 54 older adults (>= 50 years of age) was
      carried out in Costa Rica. In a moderated mediation analysis, action control was
      specified as a mediator between self-efficacy and physical activity, whereas
      social support was specified as a moderator between self-efficacy and action
      control. Baseline physical activity, age, and sex were specified as covariates.
      RESULTS: Action control mediated between self-efficacy and physical activity. An
      interaction between social support and self-efficacy on action control pointed to
      a synergistic effect at the first stage of the mediating process. CONCLUSIONS:
      The effect of self-efficacy on physical activity was partly explained by action
      control, providing evidence of action control as a proximal mediator of physical
      activity. Moreover, the moderator role of social support was confirmed: high
      social support appeared to compensate for low levels of self-efficacy.

PMID- 24733274
TI  - Recurrent small bowel obstruction in a 60-year-old celiac patient: a rare entity
      of a common disease.
AB  - A 60-year-old woman with a medical history of celiac disease was evaluated due to
      recurrent episodes of small bowel obstruction. Upper and lower endoscopies were
      normal. The small bowel pathology consisted of celiac disease, and the anti
      endomysial antibody was positive. Dilatation of small bowel loops was
      demonstrated on abdominal computed tomography. Further evaluation was conducted
      using video capsule endoscopy that demonstrated regional narrowing and severe
      ulceration in the middle of the small bowel. Upper and lower double balloon
      endoscopies failed to demonstrate the lesion. On explorative laparotomy a small
      bowel mass in the proximal ileum was excised. Pathology revealed ulcerated, well
      to moderately differentiated adenocarcinoma without regional nodal involvement.
      We discuss the etiology and treatment of small bowel carcinoma. This case
      emphasizes that a high level of suspicion is required in order to diagnose early
      stage small bowel adenocarcinoma in celiac patients.

PMID- 24733275
TI  - A tribute to Max L. Deinzer (June 19, 1937-May 20, 2013).

PMID- 24733273
TI  - Meta-analysis of the association between COX-2 polymorphisms and risk of
      colorectal cancer based on case-control studies.
AB  - OBJECTIVE: Cyclooxygenase-2 (COX-2) is an inducible enzyme converting arachidonic
      acid to prostaglandins and playing important roles in inflammatory diseases as
      well as tumor development. Previous studies investigating the association between
      COX-2 polymorphisms and colorectal cancer (CRC) risk reported conflicting
      results. We performed a meta-analysis of all available studies to explore this
      association. METHODS: All studies published up to October 2013 on the association
      between COX-2 polymorphisms and CRC risk were identified by searching electronic
      databases PubMed, EMBASE, and Cochrane library. The association between COX-2
      polymorphisms and CRC risk was assessed by odds ratios (ORs) together with their
      95% confidence intervals (CIs). RESULTS: Ten studies with 6,774 cases and 9,772
      controls were included for -1195A>G polymorphism, 13 studies including 6,807
      cases and 10,052 controls were available for -765G>C polymorphism, and 8 studies
      containing 5,121 cases and 7,487 controls were included for 8473T>C polymorphism.
      With respect to -765G>C polymorphism, we did not find a significant association
      with CRC risk when all eligible studies were pooled into the meta-analysis.
      However, in subgroup analyses by ethnicity and cancer location, with a Bonferroni
      corrected alpha of 0.05/2, statistical significant increased CRC risk was found
      in the Asian populations (dominant model CC+CG vs. GG: OR = 1.399, 95%CI: 1.113
      1.760, P = 0.004) and rectum cancer patients (CC vs. GG: OR = 2.270, 95%CI: 1.295
      3.980, P = 0.004; Recessive model CC vs. CG+GG: OR = 2.269, 95%CI: 1.297-3.970, P
      = 0.004). In subgroup analysis according to source of control, no significant
      association was detected. With respect to -1195A>G and 8473T>C polymorphisms, no
      significant association with CRC risk was demonstrated in the overall and
      subgroup analyses. CONCLUSIONS: The present meta-analysis suggests that the COX-2
      -765G>C polymorphism may be a risk factor for CRC in Asians and rectum cancer
      patients. Further large and well-designed studies are needed to confirm this
      association.

PMID- 24733276
TI  - Soft supercharging of biomolecular ions in electrospray ionization mass
      spectrometry.
AB  - The charge states of biomolecular ions in ESI-MS can be significantly increased
      by the addition of low-vapor supercharging (SC) reagents into the spraying
      solution. Despite the considerable interest from the community, the mechanistic
      aspects of SC are not well understood and are hotly debated. Arguments that
      denaturation accounts for the increased charging observed in proteins sprayed
      from aqueous solutions containing SC reagent have been published widely, but
      often with incomplete or ambiguous supporting data. In this work, we explored ESI
      MS charging and SC behavior of several biopolymers including proteins and DNA
      oligonucleotides. Analytes were ionized from 100 mM ammonium acetate (NH4Ac)
      aqueous buffer in both positive (ESI+) and negative (ESI-) ion modes. SC was
      induced either with m-NBA or by the elevated temperature of ESI capillary. For
      all the analytes studied we, found striking differences in the ESI MS response to
      these two modes of activation. The data suggest that activation with m-NBA
      results in more extensive analyte charging with lower degree of denaturation.
      When working solution with m-NBA was analyzed at elevated temperatures, the SC
      effect from m-NBA was neutralized. Instead, the net SC effect was similar to the
      SC effect achieved by thermal activation only. Overall, our observations indicate
      that SC reagents enhance ESI charging of biomolecules via distinctly different
      mechanism compared with the traditional approaches based on analyte denaturation.
      Instead, the data support the hypothesis that the SC phenomenon involves a direct
      interaction between a biopolymer and SC reagent occurring in evaporating ESI
      droplets. 

PMID- 24733277
TI  - Collaborative care for depression and anxiety disorders in patients with recent
      cardiac events: the Management of Sadness and Anxiety in Cardiology (MOSAIC)
      randomized clinical trial.
AB  - IMPORTANCE: Depression and anxiety are associated with adverse cardiovascular
      outcomes in patients with recent acute cardiac events. There has been minimal
      study of collaborative care (CC) management models for mental health disorders in
      high-risk cardiac inpatients, and no prior CC intervention has simultaneously
      managed depression and anxiety disorders. OBJECTIVE: To determine the impact of a
      low-intensity CC intervention for depression, generalized anxiety disorder, and
      panic disorder among patients hospitalized for an acute cardiac illness. DESIGN,
      SETTING, AND PARTICIPANTS: Single-blind randomized clinical trial, with study
      assessors blind to group assignment, from September 2010 through July 2013 of 183
      patients admitted to inpatient cardiac units in an urban academic general
      hospital for acute coronary syndrome, arrhythmia, or heart failure and found to
      have clinical depression, generalized anxiety disorder, or panic disorder on
      structured assessment. INTERVENTIONS: Participants were randomized to 24 weeks of
      a low-intensity telephone-based multicomponent CC intervention targeting
      depression and anxiety disorders (n = 92) or to enhanced usual care (serial
      notification of primary medical providers; n = 91). The CC intervention used a
      social work care manager to coordinate assessment and stepped care of psychiatric
      conditions and to provide support and therapeutic interventions as appropriate.
      MAIN OUTCOMES AND MEASURES: Improvement in mental health-related quality of life
      (Short Form-12 Mental Component Score [SF-12 MCS]) at 24 weeks, compared between
      groups using a random-effects model in an intent-to-treat analysis. RESULTS:
      Patients randomized to CC had significantly greater estimated mean improvements
      in SF-12 MCS at 24 weeks (11.21 points [from 34.21 to 45.42] in the CC group vs
      5.53 points [from 36.30 to 41.83] in the control group; estimated mean
      difference, 5.68 points [95% CI, 2.14-9.22]; P = .002; effect size, 0.61).
      Patients receiving CC also had significant improvements in depressive symptoms
      and general functioning, and higher rates of treatment of a mental health
      disorder; anxiety scores, rates of disorder response, and adherence did not
      differ between groups. CONCLUSIONS AND RELEVANCE: A novel telephone-based, low
      intensity model to concurrently manage cardiac patients with depression and/or
      anxiety disorders was effective for improving mental health-related quality of
      life in a 24-week trial. TRIAL REGISTRATION: clinicaltrials.gov Identifier:
      NCT01201967.

PMID- 24733278
TI  - Perioperative chemotherapy for muscle-invasive bladder cancer: A population-based
      outcomes study.
AB  - BACKGROUND: Practice guidelines recommend neoadjuvant chemotherapy (NACT) for
      bladder cancer. However, the evidence in support of adjuvant chemotherapy (ACT)
      is less robust. Here we describe whether the evidence of efficacy for NACT/ACT
      was sufficient to change clinical practice and whether the efficacy demonstrated
      in clinical trials was translated into effectiveness in the general population.
      METHODS: Electronic records of treatment were linked to the population-based
      Ontario Cancer Registry to identify all patients with bladder cancer treated with
      cystectomy in Ontario 1994-2008. Utilization of NACT/ACT was compared across 1994
      1998, 1999-2003, and 2004-2008. Logistic regression was used to analyze factors
      associated with NACT/ACT. Cox model and propensity score analyses were used to
      explore the association between ACT and survival. RESULTS: Two thousand forty
      four patients underwent cystectomy for muscle-invasive bladder cancer (MIBC). Use
      of NACT remained stable (mean, 4%), whereas utilization of ACT increased over
      time (16%, 18%, 22%; P = .001). Advanced stage (T3/T4; OR, 1.83; 95% CI, 1.38
      2.46) and node-positive disease (OR, 8.10; 95% CI, 6.20-10.7) were associated
      with greater utilization of ACT. Five-year overall survival (OS) and cancer
      specific survival (CSS) for all patients was 29% (95% CI, 28%-31%) and 33% (95%
      CI, 31%-35%), respectively. Utilization of ACT was associated with improved OS
      (HR, 0.71; 95% CI, 0.62-0.81) and CSS (HR, 0.73; 95% CI, 0.64-0.84). Results were
      consistent in propensity score analyses. CONCLUSIONS: NACT remains substantially
      underutilized in routine clinical practice. Our results suggest that
      perioperative chemotherapy is associated with a substantial survival benefit in
      the general population. Patients who are planning to undergo cystectomy for
      bladder cancer should be reviewed by a multidisciplinary team.

PMID- 24733279
TI  - The impact of ambient particle pollution during extreme-temperature days in
      Guangzhou City, China.
AB  - The aim of this study is to explore whether the effect of PM10 (particulate
      matter with an aerodynamic diameter of <10 um) on daily mortality was modified by
      extreme temperatures in Guangzhou from 2005 to 2009. The present study used time
      series analysis to explore the modification effects of temperature on the
      association between PM10 and the cause-specific mortalities for cardiovascular,
      respiratory, cardiopulmonary, and nonaccidental mortality. The interactions
      between PM10 and temperature were statistically significant on respiratory
      mortality. The effect estimates per 10-ug/m(3) increase in PM10 concentrations at
      the moving average of lags of 0 and 1 day on high-temperature days were 2.34%
      (95% confidence interval = 0.55, 4.16) for nonaccidental, 1.35% (-1.69, 4.48) for
      cardiovascular, 6.09% (2.42, 9.89) for respiratory, and 3.36% (0.92, 5.86) for
      cardiopulmonary mortalities. The results suggest that it is important to control
      and reduce the emission of air particles in Guangzhou, particularly on extreme
      high-temperature days.

PMID- 24733280
TI  - The association of market competition with hospital charges, length of stay, and
      quality outcomes for patients with joint diseases: a longitudinal study in Korea.
AB  - This study investigated the association of market competition with hospital
      charges, length of stay, and quality outcomes. A total of 279,847 patients from
      851 hospitals were analyzed. The Herfindahl-Hirschman Index was used as a measure
      of hospital market competition level. Our results suggest that hospitals in less
      competitive markets charged more on charge per admission, possibly by increasing
      the length of stays, however, hospitals in more competitive markets charged more
      for daily services by providing more intensive services while reducing the length
      of stays, thereby reducing the overall charge per admission. Quality outcomes
      measured by mortality within 30 days of admission and readmission within 30 days
      of discharge were better for surgical procedures within competitive areas.
      Continued government monitoring of hospital response to market competition level
      is recommended in order to determine whether changes in hospitals' strategies
      influence the long-term outcomes of services performance and health care
      spending. 

PMID- 24733281
TI  - A logistic regression model for estimating transport accident deaths using verbal
      autopsy data.
AB  - This study aimed to create an appropriate model using verbal autopsy (VA) data to
      estimate transport accident deaths from vital registration data in Thailand. A
      sample of 9644 VA deaths was obtained from the Thai Ministry of Public Health. VA
      assessed transport accidents accounted for 546 deaths (5.7% of sample). Logistic
      regression was used to model transport accident deaths classified by 9 provinces,
      16 gender-age groups, 14 combinations of vital reported cause groups, and place
      of death (in or outside hospital). The receiver operating characteristic curve
      was used to match the number of reported transport accident deaths to the number
      predicted by the model with sensitivity 73.8% and false positive rate 1.6%. The
      estimated transport accident deaths ranged from 1.68 to 2.65 times higher than
      the vital registration data reported according to gender-age groups. 

PMID- 24733282
TI  - Effectiveness of the diode laser in the treatment of ligature-induced
      periodontitis in rats: a histopathological, histometric, and immunohistochemical
      study.
AB  - The aim of this study was to evaluate the effects of the use of a high-power
      gallium-aluminum-arsenide diode laser (GaAlAs; 808 nm, 1 W, 20 s, 20 Hz, 10 J)
      alone or as adjunctive therapy to scaling and root planing in the treatment of
      induced periodontitis in rats. Periodontitis was induced by placing a ligature
      around the mandibular first molar of 60 rats. After 7 days, the ligature was
      removed and the animals were divided into four groups as follows: C (control), no
      periodontal treatment; SRP, scaling and root planing (SRP); DL, diode laser (DL)
      irradiation treatment; and SRP/DL, both SRP and DL irradiation treatment. Five
      animals from each group were euthanized at 7, 15, and 30 days posttreatment. The
      effectiveness of the treatments was evaluated in the furcation area using
      histopathological analysis, histometric analysis of alveolar bone loss (ABL), and
      immunohistochemical detection of tartrate-resistant acid phosphatase (TRAP), runt
      related transcription factor 2 (RUNX2), and osteocalcin (OCN). DL, alone or in
      combination with adjunctive therapy to SRP in the treatment of experimental
      periodontitis, resulted in a decreased local inflammatory response. At 7-days
      posttreatment, the DL and SRP/DL groups had fewer TRAP-positive cells and more
      RUNX2-positive cells. There was greater OCN immunolabeling in the DL group than
      in the C and SRP groups at 15 days. There was less ABL in the DL and SRP/DL
      groups at 15 and 30 days. In conclusion, DL was effective in the treatment of
      ligature-induced periodontitis in rats, both when used alone and when used as
      adjunctive therapy to SRP.

PMID- 24733283
TI  - The effect of low-level laser therapy on knee osteoarthritis: prospective,
      descriptive study.
AB  - BACKGROUND: Osteoarthritis (OA) is one of the most common joint disorders in the
      elderly which could be associated with considerable physical disability. PATIENTS
      AND METHODS: In a descriptive, prospective study, 33 patients enrolled in the
      study from which 15 people were excluded due to incomplete course of treatment,
      leaving the total number of 18 patients with knee osteoarthritis. Gal-Al-As diode
      laser device was used as a source of low-power laser. Patients were performed
      laser therapy with a probe of LO7 with a wavelength of 810 nm and 50 mW output
      power in pulse radiation mode (F = 3,000, peak power = 80 W, Deltat = 200 ns,
      density = 0.05 W/cm(2), dose = 6 J/cm(2), area = 1 cm(2)) and also a probe of
      MLO1K with a power output of 30 mW and a wavelength of 890 nm in pulse radiation
      mode (F = 3,000 Hz, peak power = 50 W, Deltat = 200 ns, density = 0.017 W/cm(2),
      total dose = 10 J/cm(2)), and were given low-level laser therapy (LLLT) three
      times a week with a total number of 12 sessions. Data were analyzed using SPSS
      ver. 15, and the obtained data were reported as mean +/- SD and frequency (%). To
      analyze the data, repeated measurement and marginal homogeneity approaches were
      used. RESULTS: In the current study, a significant reduction was observed
      regarding the nocturnal pain, pain on walking and ascending the steps, knee
      circumference, distance between the hip and heel, and knee to horizontal hip to
      heel distance at the end of the treatment course. CONCLUSIONS: In brief, the
      current study focuses on the fact that LLLT is effective in reducing pain in knee
      osteoarthritis.

PMID- 24733286
TI  - Palladium-catalyzed regioselective azidation of allylic C-H bonds under
      atmospheric pressure of dioxygen.
AB  - A palladium-catalyzed allylic azidation of alkenes with sodium azide under
      atmospheric pressure of dioxygen was developed. This methodology provides a new
      efficient and simple route for accessing allylic azides. Furthermore, the one-pot
      process consisting of Pd-catalyzed allylic azidation of alkenes and Cu-catalyzed
      1,3-dipolar cycloaddition led directly to the 1,2,3-triazole from the alkene. The
      formed allylic azide can be also in situ reduced to the allylic amine or oxidized
      to the alkenyl nitrile. 

PMID- 24733287
TI  - Plasmonic Fano resonances in metallic nanorod complexes.
AB  - Plasmonic Fano resonances (FRs) in nanostructures have been extensively studied
      in recent years. Nanorod-based complexes for FRs have also attracted much
      attention. The basic optical properties and fabrication technology of different
      kinds of plasmonic nanorods have been greatly developed over the last several
      years. The mutipole plasmon resonances and their flexible adjustment ranges on
      nanorods make them promising for FR modifications and structure diversity. In
      this paper, we review some recently studied plasmonic nanorod based
      nanostructures for FRs, including single nanorods, dimers, mutipole rods and
      nanorod-nanoparticle hybrids. The corresponding applications of the FRs are also
      briefly discussed. 

PMID- 24733284
TI  - In high-light-acclimated coffee plants the metabolic machinery is adjusted to
      avoid oxidative stress rather than to benefit from extra light enhancement in
      photosynthetic yield.
AB  - Coffee (Coffea arabica L.) has been traditionally considered as shade-demanding,
      although it performs well without shade and even out-yields shaded coffee. Here
      we investigated how coffee plants adjust their metabolic machinery to varying
      light supply and whether these adjustments are supported by a reprogramming of
      the primary and secondary metabolism. We demonstrate that coffee plants are able
      to adjust its metabolic machinery to high light conditions through marked
      increases in its antioxidant capacity associated with enhanced consumption of
      reducing equivalents. Photorespiration and alternative pathways are suggested to
      be key players in reductant-consumption under high light conditions. We also
      demonstrate that both primary and secondary metabolism undergo extensive
      reprogramming under high light supply, including depression of the levels of
      intermediates of the tricarboxylic acid cycle that were accompanied by an up
      regulation of a range of amino acids, sugars and sugar alcohols, polyamines and
      flavonoids such as kaempferol and quercetin derivatives. When taken together, the
      entire dataset is consistent with these metabolic alterations being primarily
      associated with oxidative stress avoidance rather than representing adjustments
      in order to facilitate the plants from utilizing the additional light to improve
      their photosynthetic performance. 

PMID- 24733288
TI  - Phosphine-catalyzed sequential annulation domino reaction: rapid construction of
      bicyclo[4.1.0]heptene skeletons.
AB  - A convenient and efficient phosphine-catalyzed sequential annulation domino
      reaction between dienic sulfones and MBH carbonates has been developed. In the
      presence of 20 mol% of tris(4-fluorophenyl)phosphine, functionalized
      bicyclo[4.1.0]heptenes were prepared in excellent yields and stereoselectivities
      under mild conditions. 

PMID- 24733289
TI  - Evidence for the effectiveness of walking training on walking and self-care after
      stroke: a systematic review and meta-analysis of randomized controlled trials.
AB  - OBJECTIVE: To examine the effect of randomized controlled trials of walking
      training on walking and self-care in patients with stroke. DATA SOURCES: MEDLINE,
      CINAHL, Embase, PEDro, OTSeeker, Central, and manual search to the end of August
      2012. STUDY SELECTION: English, Finnish, Swedish, or German language walking
      training randomized controlled trials for patients over 18 years of age with
      stroke. DATA SYNTHESIS: The meta-analyses included 38 randomized controlled
      trials from 44 reports. There was high evidence that in the subacute stage of
      stroke, specific walking training resulted in improved walking speed and distance
      compared with traditional walking training of the same intensity. In the chronic
      stage, walking training resulted in increased walking speed and walking distance
      compared with no/placebo treatment, and increased walking speed compared with
      overall physio-therapy. On average, 24 training sessions for 7 weeks were needed.
      CONCLUSION: Walking training improves walking capacity and, to some extent, self
      care in different stages of stroke, but the training frequency should be fairly
      high.

PMID- 24733290
TI  - Rhinitis symptoms and asthma among parents of preschool children in relation to
      the home environment in Chongqing, China.
AB  - Risk factors for rhinitis and asthma in the home environment were studied by a
      questionnaire survey. Parents of 4530 1-8 year old children (one parent per
      child) from randomly selected kindergartens in Chongqing, China participated.
      70.4% were females; 47.1% had rhinitis symptoms in the last three months (current
      rhinitis, CR); 1.6% reported a history of allergic asthma (AA); 2.7% reported a
      history of allergic rhinitis (AR); 16.4% were current smokers; 50.8% males and
      2.4% females were current smokers. Stuffy odor, unpleasant odor, tobacco smoke
      odor and dry air were associated with CR (adjustment for gender, current smoking
      and other perceptions of odor or humidity). Associations between home environment
      and CR, AR, and AA were studied by multiple logistic regression analyses,
      adjusting for gender, current smoking and other significant home factors. Living
      near a main road or highway was a risk factor for both CR (OR(95%CI):
      1.31(1.13,1.52)) and AR (OR(95%CI): 2.44(1.48,4.03)). Other risk factors for CR
      included living in rural areas (OR(95%CI): 1.43(1.10,1.85)), new furniture
      (OR(95%CI): 1.28(1.11,1.49)), water damage (OR(95%CI): 1.68(1.29,2.18)),
      cockroaches (OR(95%CI): 1.46(1.23,1.73)), and keeping pets (OR(95%CI):
      1.24(1.04,1.49)). Other risk factors for AR included redecoration (OR(95%CI):
      2.14(1.34,3.41)), mold spots (OR(95%CI): 2.23(1.06,4.68)), window pane
      condensation (OR(95%CI): 2.04(1.28,3.26)). Water damage was the only home factor
      associated with AA (2.56(1.34,4.86)). Frequently put bedding to sunshine was
      protective for CR (OR(95%CI): 0.79(0.68,0.92); cleaning every day was protective
      for AR (OR(95%CI): 0.40(0.22,0.71)). In conclusion, parents' CR and AR were
      related to a number of factors of the home environment. 

PMID- 24733291
TI  - R PheWAS: data analysis and plotting tools for phenome-wide association studies
      in the R environment.
AB  - Phenome-wide association studies (PheWAS) have been used to replicate known
      genetic associations and discover new phenotype associations for genetic
      variants. This PheWAS implementation allows users to translate ICD-9 codes to
      PheWAS case and control groups, perform analyses using these and/or other
      phenotypes with covariate adjustments and plot the results. We demonstrate the
      methods by replicating a PheWAS on rs3135388 (near HLA-DRB, associated with
      multiple sclerosis) and performing a novel PheWAS using an individual's maximum
      white blood cell count (WBC) as a continuous measure. Our results for rs3135388
      replicate known associations with more significant results than the original
      study on the same dataset. Our PheWAS of WBC found expected results, including
      associations with infections, myeloproliferative diseases and associated
      conditions, such as anemia. These results demonstrate the performance of the
      improved classification scheme and the flexibility of PheWAS encapsulated in this
      package. AVAILABILITY AND IMPLEMENTATION: This R package is freely available
      under the Gnu Public License (GPL-3) from http://phewascatalog.org. It is
      implemented in native R and is platform independent.

PMID- 24733292
TI  - Association analysis using next-generation sequence data from publicly available
      control groups: the robust variance score statistic.
AB  - MOTIVATION: Sufficiently powered case-control studies with next-generation
      sequence (NGS) data remain prohibitively expensive for many investigators. If
      feasible, a more efficient strategy would be to include publicly available
      sequenced controls. However, these studies can be confounded by differences in
      sequencing platform; alignment, single nucleotide polymorphism and variant
      calling algorithms; read depth; and selection thresholds. Assuming one can match
      cases and controls on the basis of ethnicity and other potential confounding
      factors, and one has access to the aligned reads in both groups, we investigate
      the effect of systematic differences in read depth and selection threshold when
      comparing allele frequencies between cases and controls. We propose a novel
      likelihood-based method, the robust variance score (RVS), that substitutes
      genotype calls by their expected values given observed sequence data. RESULTS: We
      show theoretically that the RVS eliminates read depth bias in the estimation of
      minor allele frequency. We also demonstrate that, using simulated and real NGS
      data, the RVS method controls Type I error and has comparable power to the 'gold
      standard' analysis with the true underlying genotypes for both common and rare
      variants. AVAILABILITY AND IMPLEMENTATION: An RVS R script and instructions can
      be found at strug.research.sickkids.ca, and at https://github.com/strug-lab/RVS.
      CONTACT: lisa.strug@utoronto.ca SUPPLEMENTARY INFORMATION: Supplementary data are
      available at Bioinformatics online.

PMID- 24733294
TI  - Body mass index is associated with appropriateness of weight gain but not leisure
      time physical activity during pregnancy.
AB  - BACKGROUND: Little is known about how leisure-time physical activity (LTPA)
      influences gestational weight gain (GWG) among body mass index (BMI) categories.
      The purpose of this study was to examine the relationship between pregnancy LTPA
      and the proportion of normal, overweight, and obese women who meet GWG
      recommendations. METHODS: Participants included 449 subcohort women from the
      Pregnancy Outcomes and Community Health (POUCH) study. LTPA was collapsed into 3
      categories [(None, < 7.5 kcal/kg/wk (low), >= 7.5 kcal/kg/wk (recommended)]. GWG
      was categorized according to IOM recommendations (low, recommended, or excess).
      Chi-square and logistic regression analyses were used to evaluate relationships
      among LTPA, BMI, and GWG. RESULTS: Overweight women were more likely to have high
      GWG vs. normal weight women (OR = 2.3, 95% CI 1.3-4.0). Obese women were more
      likely to experience low GWG (OR = 7.3, 95% CI 3.6-15.1; vs. normal and
      overweight women) or excess GWG (OR = 3.5, 95% CI 1.9-6.5; vs. normal weight
      women). LTPA did not vary by prepregnancy BMI category (P = .55) and was not
      related to GWG in any prepregnancy BMI category (P = .78). CONCLUSIONS:
      Regardless of prepregnancy BMI, LTPA did not affect a woman's GWG according to
      IOM recommendations. Results may be due to LTPA not differing among BMI
      categories.

PMID- 24733293
TI  - Glucagon stimulates hepatic FGF21 secretion through a PKA- and EPAC-dependent
      posttranscriptional mechanism.
AB  - Previous studies have shown that whole body deletion of the glucagon receptor
      suppresses the ability of starvation to increase hepatic fibroblast growth factor
      21 (FGF21) expression and plasma FGF21 concentration. Here, we investigate the
      mechanism by which glucagon receptor activation increases hepatic FGF21
      production. Incubating primary rat hepatocyte cultures with glucagon, dibutyryl
      cAMP or forskolin stimulated a 3-4-fold increase in FGF21 secretion. The effect
      of these agents on FGF21 secretion was not associated with an increase in FGF21
      mRNA abundance. Glucagon induction of FGF21 secretion was additive with the
      stimulatory effect of a PPARalpha activator (GW7647) on FGF21 secretion.
      Inhibition of protein kinase A (PKA) and downstream components of the PKA pathway
      [i.e. AMP-activated protein kinase and p38 MAPK] suppressed glucagon activation
      of FGF21 secretion. Incubating hepatocytes with an exchange protein directly
      activated by cAMP (EPAC)-selective cAMP analog [i.e. 8-(4-chlorophenylthio)-2'-O
      methyladenosine-3', 5'-cyclic monophosphate (cpTOME)], stimulated a 3.9-fold
      increase FGF21 secretion, whereas inhibition of the EPAC effector, Rap1,
      suppressed glucagon activation of FGF21 secretion. Treatment of hepatocytes with
      insulin also increased FGF21 secretion. In contrast to glucagon, insulin
      activation of FGF21 secretion was associated with an increase in FGF21 mRNA
      abundance. Glucagon synergistically interacted with insulin to stimulate a
      further increase in FGF21 secretion and FGF21 mRNA abundance. These results
      demonstrate that glucagon increases hepatic FGF21 secretion via a
      posttranscriptional mechanism and provide evidence that both the PKA branch and
      EPAC branch of the cAMP pathway play a role in mediating this effect. These
      results also identify a novel synergistic interaction between glucagon and
      insulin in the regulation of FGF21 secretion and FGF21 mRNA abundance. We propose
      that this insulin/glucagon synergism plays a role in mediating the elevation in
      FGF21 production during starvation and conditions related to metabolic syndrome. 

PMID- 24733295
TI  - How and how well do pediatric radiology fellows learn ultrasound skills? A
      national survey.
AB  - BACKGROUND: Ultrasound (US) comprises a significant portion of pediatric imaging.
      Technical as well as interpretive skills in US imaging are consequently
      fundamental in training pediatric radiologists. Unfortunately, formalized
      technical education regarding US imaging in pediatric fellowships has lagged.
      OBJECTIVE: We surveyed pediatric fellows and program directors regarding US
      scanning education to improve this experience moving forward. MATERIALS AND
      METHODS: We conducted an online survey from February 2011 to March 2011 of all
      United States pediatric radiology body imaging fellows and fellowship program
      directors. Questions posed to fellows assessed their educational US experiences
      during their residencies and fellowships. Directors were asked to evaluate US
      educational opportunities in their programs. RESULTS: Among the respondents,
      43.9% of fellows undertook on-call US scanning without a sonographer during
      residency, 23.3% during fellowship; 41.8% of fellows and 58.6% of program
      directors reported that their fellowship had a dedicated curriculum to facilitate
      independent US scanning. Both fellows and program directors cited the volume of
      cases requiring immediate dictation as an obstacle to scanning. Fewer program
      directors than fellows identified lack of sufficient staffing as an obstacle, but
      more identified fellow disinterest. Program directors and fellows alike rated
      independent US scanning as highly important to pediatric radiologists' future
      success. CONCLUSION: Pediatric radiology fellowship directors and fellows agree
      that technical US skills are crucial to the practice of pediatric radiology.
      However, the groups identify different obstacles to training. As US instruction
      is developing in undergraduate medicine and subspecialists are acquiring point-of
      care US skills, pediatric radiology education should address the obstacles to US
      training and formalize a curriculum at the fellowship level.

PMID- 24733296
TI  - Dissociable influences of reward motivation and positive emotion on cognitive
      control.
AB  - It is becoming increasingly appreciated that affective and/or motivational
      influences contribute strongly to goal-oriented cognition and behavior. An
      unresolved question is whether emotional manipulations (i.e., direct induction of
      affectively valenced subjective experience) and motivational manipulations (e.g.,
      delivery of performance-contingent rewards and punishments) have similar or
      distinct effects on cognitive control. Prior work has suggested that reward
      motivation can reliably enhance a proactive mode of cognitive control, whereas
      other evidence is suggestive that positive emotion improves cognitive
      flexibility, but reduces proactive control. However, a limitation of the prior
      research is that reward motivation and positive emotion have largely been studied
      independently. Here, we directly compared the effects of positive emotion and
      reward motivation on cognitive control with a tightly matched, within-subjects
      design, using the AX-continuous performance task paradigm, which allows for
      relative measurement of proactive versus reactive cognitive control. High
      resolution pupillometry was employed as a secondary measure of cognitive dynamics
      during task performance. Robust increases in behavioral and pupillometric indices
      of proactive control were observed with reward motivation. The effects of
      positive emotion were much weaker, but if anything, also reflected enhancement of
      proactive control, a pattern that diverges from some prior findings. These
      results indicate that reward motivation has robust influences on cognitive
      control, while also highlighting the complexity and heterogeneity of positive
      emotion effects. The findings are discussed in terms of potential neurobiological
      mechanisms. 

PMID- 24733298
TI  - Pleural effusion from leaky diaphragm--the hepatic hydrothorax.

PMID- 24733297
TI  - Phase variation in Myxococcus xanthus yields cells specialized for iron
      sequestration.
AB  - Myxococcus xanthus undergoes phase variation during growth to produce
      predominantly two colony phenotypes. The majority are yellow colonies containing
      swarm-proficient cells and a minority are tan colonies containing swarm-deficient
      cells. Comparison of the transcriptomes of a yellow variant, a tan variant, and
      three tan mutants led to the identification of differentially-regulated genes
      that define key segments of the phase variation pathway. For example, expression
      of genes for the yellow pigment DKxanthene and the antibiotic myxovirescin was
      increased significantly in yellow variants. In contrast, expression of the
      siderophore myxochelin, hemin binding proteins, and iron transport proteins was
      increased specifically in tan strains. Thus, a consequence of phase variation is
      that yellow cells shift from producing antibiotic and pigment to producing
      components involved in acquisition of iron, which may increase fitness during
      periods of iron limitation. Multiple protein kinases and HTH-Xre DNA-binding
      proteins identified in this study may be involved in the regulatory hierarchy
      that governs phase variation. 

PMID- 24733299
TI  - Addressing the nation's physician workforce needs: The Society of General
      Internal Medicine (SGIM) recommendations on graduate medical education reform.
AB  - The Graduate Medical Education (GME) system in the United States (US) has
      garnered worldwide respect, graduating over 25,000 new physicians from over 8,000
      residency and fellowship programs annually. GME is the portal of entry to medical
      practice and licensure in the US, and the pathway through which resident
      physicians develop the competence to practice independently and further develop
      their career plans. The number and specialty distribution of available GME
      positions shapes the overall composition of our national workforce; however, GME
      is failing to provide appropriate programs that support the delivery of our
      society's system of healthcare. This paper, prepared by the Health Policy
      Education Subcommittee of the Society of General Internal Medicine (SGIM) and
      unanimously endorsed by SGIM's Council, outlines a set of recommendations on how
      to reform the GME system to best prepare a physician workforce that can provide
      high quality, high value, population-based, and patient-centered health care,
      aligned with the dynamic needs of our nation's healthcare delivery system. These
      recommendations include: accurate workforce needs assessment, broadened GME
      funding sources, increased transparency of the use of GME dollars, and
      implementation of incentives to increase the accountability of GME-funded
      programs for the preparation and specialty selection of their program graduates.

PMID- 24733300
TI  - Clinical image: clubbed with a reminder to test for HIV.

PMID- 24733302
TI  - MRI diagnosis of rupture of pancreatic pseudocyst into portal vein: case report
      and review of literature.
AB  - Rupture into the portal vein is a rare complication of a pancreatic pseudocyst.
      Only 15 cases of such an incidence have been described in the literature. Only
      one of these was diagnosed with magnetic resonance imaging (MRI), the rest being
      diagnosed using other invasive diagnostic modalities or at surgery. We report a
      case of this rare complication diagnosed on MRI and also describe the
      demonstration of residual lysed thrombus within the portal vein as a new feature
      on MRI which supports this diagnosis. The presence of liver necrosis present in
      our case is a probable effect of this complication not described in the
      literature before. Early diagnosis of this potentially lethal complication can
      help in the proper management of these patients.

PMID- 24733301
TI  - Effectiveness and safety of patient activation interventions for adults with type
      2 diabetes: systematic review, meta-analysis, and meta-regression.
AB  - BACKGROUND: Patient activation interventions (PAIs) engage patients in care by
      promoting increased knowledge, confidence, and/or skills for disease self
      management. However, little is known about the impact of these interventions on a
      wide range of outcomes for adults with type 2 diabetes (DM2), or which of these
      interventions, if any, have the greatest impact on glycemic control. METHODS:
      Electronic databases were searched from inception through November 2011. Of
      16,290 citations, two independent reviewers identified 138 randomized trials
      comparing PAIs to usual care/control groups in adults with DM2 that reported
      intermediate or long-term outcomes or harms. For meta-analyses of continuous
      outcomes, we used a random-effects model to derive pooled weighted mean
      differences (WMD). For all-cause mortality, we calculated the pooled odds ratio
      (OR) using Peto's method. We assessed statistical heterogeneity using the I (2)
      statistic and conducted meta-regression using a random-effects model when I (2) >
      50 %. A priori meta-regression primary variables included: intervention
      strategies, intervention leader, baseline outcome value, quality, and study
      duration. RESULTS: PAIs modestly reduced intermediate outcomes [A1c: WMD 0.37 %,
      CI 0.28-0.45 %, I (2) 83 %; SBP: WMD 2.2 mmHg, CI 1.0-3.5 mmHg, I (2) 72 %; body
      weight: WMD 2.3 lbs, CI 1.3-3.2 lbs, I (2) 64 %; and LDL-c: WMD 4.2 mg/dL, CI 1.5
      6.9 mg/dL, I (2) 64 %]. The evidence was moderate for A1c, low/very low for other
      intermediate outcomes, low for long-term mortality and very low for
      complications. Interventions had no effect on hypoglycemia (evidence: low) or
      short-term mortality (evidence: moderate). Higher baseline A1c, pharmacist-led
      interventions, and longer follow-up were associated with larger A1c improvements.
      No intervention strategy outperformed any other in adjusted meta-regression.
      CONCLUSIONS: PAIs modestly improve A1c in adults with DM2 without increasing
      short-term mortality. These results support integration of these interventions
      into primary care for adults with uncontrolled glycemia, and provide evidence to
      insurers who do not yet cover these programs.

PMID- 24733303
TI  - [Suicidal drug overdose while receiving palliative home care: a case report].
AB  - Suicidal thoughts are a common phenomenon in palliative care which can be seen in
      around 10% of the patients. There is very little knowledge about attempted and
      committed suicide. This article is a case report about a patient with lung cancer
      in a terminal state of illness who ingested drugs in a toxic dose while receiving
      palliative home care. This article deals with ethical issues in medical treatment
      and various ways of decision-making.

PMID- 24733304
TI  - [High-intensity interval training for young athletes].
AB  - A computer-based literature research during July 2013 using the electronic
      databases PubMed, MEDLINE, SPORTDiscus and Web of Science was performed to assess
      the effect of the high intensity interval training (HIIT) on sport performance in
      healthy children and adolescents. Studies examining the effect of HIIT on aerobic
      and anaerobic performance pre and post to HIIT-Interventions in children and
      adolescents (9-18 years) were included. The results indicate increased aerobic
      and anaerobic performance following two or three HIIT sessions per week for a
      period of five to ten weeks, additional to normal training. Results regarding
      long term effects following HIIT have not been documented so far. In addition,
      due to the physiological characteris-tics during HIIT protocols improved fatigue
      resistance has been demonstrated in children as compared to adults, which may be
      interpreted as a prerequisite for the applicability of HIIT in children. 

PMID- 24733305
TI  - Bleeding risk of patients with acute venous thromboembolism taking nonsteroidal
      anti-inflammatory drugs or aspirin.
AB  - IMPORTANCE: Combined anticoagulant and aspirin therapy is associated with
      increased bleeding risk in patients with atrial fibrillation, but the bleeding
      risk of combined use of anticoagulant and nonsteroidal anti-inflammatory drugs
      (NSAIDs) is poorly documented. OBJECTIVE: To estimate the bleeding risk of
      combined anticoagulant (rivaroxaban or enoxaparin-vitamin K antagonist [VKA]) and
      NSAID or aspirin therapy in patients with venous thromboembolism. DESIGN,
      SETTING, AND PARTICIPANTS: Prospective analysis of observational data from the
      EINSTEIN deep vein thrombosis and pulmonary embolism clinical trials comparing
      rivaroxaban with enoxaparin-VKA treatment, trials performed in hospitals and
      clinics in 8246 patients enrolled from 2007 to 2009. EXPOSURE: Bleeding event
      rates during exposure to NSAID and aspirin therapy were compared to time without
      exposure. MAIN OUTCOMES AND MEASURES: Days of NSAID or aspirin use and nonuse,
      clinically relevant bleeding event and major bleeding event rates by patient
      years, and hazard ratios. RESULTS: During NSAID-anticoagulant concomitant
      treatment, clinically relevant bleeding occurred with an event rate of 37.5 per
      100 patient-years vs 16.6 per 100 patient-years during anticoagulant use only
      (hazard ratio [HR], 1.77 [95% CI, 1.46-2.14]). Major bleeding during NSAID
      anticoagulant treatment occurred with an event rate of 6.5 per 100 patient-years,
      compared to 2.0 per 100 patient-years during nonuse (HR, 2.37 [95% CI, 1.51
      3.75]). For aspirin-anticoagulant concomitant treatment, clinically relevant
      bleeding occurred with an event rate of 36.6 per 100 patient-years, compared to
      16.9 per 100 patient-years during aspirin nonuse (HR, 1.70 [95% CI, 1.38-2.11]).
      Major bleeding in aspirin-anticoagulant-treated patients occurred with an event
      rate of 4.8 per 100 patient-years, compared to 2.2 per 100 patient-years during
      aspirin nonuse (HR, 1.50 [95% CI, 0.86-2.62]). Increases in risk for clinically
      relevant and major bleeding were similar for rivaroxaban and enoxaparin-VKA
      anticoagulation regimens. CONCLUSIONS AND RELEVANCE: Among patients with venous
      thromboembolism receiving anticoagulant therapy, concomitant use of an NSAID or
      aspirin is associated with an increased risk of clinically relevant and major
      bleeding.

PMID- 24733306
TI  - Adding glycolipid functionality to model membranes--phase behaviour of a
      synthetic glycolipid in a phospholipid membrane.
AB  - Glycolipid phase behaviour is less well understood than for many phospholipids,
      but due to their structural and functional diversity, glycolipids represent an
      important group of amphiphiles from which biological function is derived. Here we
      have incorporated a synthetic glycolipid in binary mixtures with DOPC (1,2
      dioleoyl-sn-glycero-3-phosphocholine) into giant unilamellar vesicles (GUVs) at
      biologically relevant concentrations and observed the phase behaviour of the
      lipid mixtures for a range of glycolipid concentrations. At low concentrations,
      the glycolipid is fully dispersed in the GUV membrane. At glycolipid molar
      concentrations above 10%, the formation of lipid tubules is observed, and is
      consistent with the formation of a columnar lipid phase. Lipid tubules are
      observed in aqueous and oil solvents, suggesting that both hexagonal and inverted
      hexagonal lipid arrangements can be formed. This work may offer insights into the
      biological function of glycolipids and the challenges in formulating them for use
      in industrial applications. 

PMID- 24733307
TI  - Community treatment orders in New Zealand: regional variability and international
      comparisons.
AB  - OBJECTIVES: Community treatment orders (CTOs) have been used in New Zealand since
      1992 and are now used in most Commonwealth countries. There is little research on
      the rate of use of CTOs in New Zealand. This study compares the prevalence of CTO
      use across New Zealand's 20 health districts and makes comparisons with
      international prevalence rates. METHODS: New Zealand Ministry of Health reports
      provided data on rates of CTO use in New Zealand between 2005 and 2011.
      International rates were obtained from published reports and academic literature
      on CTO use. RESULTS: Rates of CTO use in New Zealand show marked and persistent
      regional variation over the period of data collection. National average rates
      increased from 58 per 100,000 in 2005 to 84 per 100,000 in 2011. Rates of use of
      CTOs are increasing internationally. New Zealand's CTO use is high by
      international comparisons. CONCLUSIONS: New Zealand's high and increasing rate of
      CTO use by international standards raises questions about the delivery and
      functioning of mental health services, and about mental health service users'
      experience of mental health care. The high rate of CTO use needs to be addressed
      as a human rights issue as well as a clinical issue.

PMID- 24733308
TI  - Zebrafish on a chip: a novel platform for real-time monitoring of drug-induced
      developmental toxicity.
AB  - Pharmaceutical safety testing requires a cheap, fast and highly efficient
      platform for real-time evaluation of drug toxicity and secondary effects. In this
      study, we have developed a microfluidic system for phenotype-based evaluation of
      toxic and teratogenic effects of drugs using zebrafish (Danio rerio) embryos and
      larvae as the model organism. The microfluidic chip is composed of two
      independent functional units, enabling the assessment of zebrafish embryos and
      larvae. Each unit consists of a fluidic concentration gradient generator and a
      row of seven culture chambers to accommodate zebrafish. To test the accuracy of
      this new chip platform, we examined the toxicity and teratogenicity of an anti
      asthmatic agent-aminophylline (Apl) on 210 embryos and 210 larvae (10 individuals
      per chamber). The effect of Apl on zebrafish embryonic development was
      quantitatively assessed by recording a series of physiological indicators such as
      heart rate, survival rate, body length and hatch rate. Most importantly, a new
      index called clonic convulsion rate, combined with mortality was used to evaluate
      the toxicities of Apl on zebrafish larvae. We found that Apl can induce deformity
      and cardiovascular toxicity in both zebrafish embryos and larvae. This
      microdevice is a multiplexed testing apparatus that allows for the examination of
      indexes beyond toxicity and teratogenicity at the sub-organ and cellular levels
      and provides a potentially cost-effective and rapid pharmaceutical safety
      assessment tool. 

PMID- 24733311
TI  - Conversion of 5-hydroxymethylfurfural to a cyclopentanone derivative by ring
      rearrangement over supported Au nanoparticles.
AB  - Supported Au nanoparticles showed efficient catalytic performance for the ring
      rearrangement of 5-hydroxymethylfurfural (HMF) to a cyclopentanone derivative, 3
      hydroxymethylcyclopentanone (HCPN), by taking advantage of the selective
      hydrogenation on Au nanoparticles and the Lewis acid catalysis of metal oxide
      supports. Among various metal oxide supported Au catalysts, the highest yield of
      HCPN was obtained by using Au/Nb2O5 (86% yield). 

PMID- 24733310
TI  - Faecal microbiota composition in adults is associated with the FUT2 gene
      determining the secretor status.
AB  - The human intestine is colonised with highly diverse and individually defined
      microbiota, which likely has an impact on the host well-being. Drivers of the
      individual variation in the microbiota compositions are multifactorial and
      include environmental, host and dietary factors. We studied the impact of the
      host secretor status, encoded by fucosyltransferase 2 (FUT2) -gene, on the
      intestinal microbiota composition. Secretor status determines the expression of
      the ABH and Lewis histo-blood group antigens in the intestinal mucosa. The study
      population was comprised of 14 non-secretor (FUT2 rs601338 genotype AA) and 57
      secretor (genotypes GG and AG) adult individuals of western European descent.
      Intestinal microbiota was analyzed by PCR-DGGE and for a subset of 12 non
      secretor subjects and 12 secretor subjects additionally by the 16S rRNA gene
      pyrosequencing and the HITChip phylogenetic microarray analysis. All three
      methods showed distinct clustering of the intestinal microbiota and significant
      differences in abundances of several taxa representing dominant microbiota
      between the non-secretors and the secretors as well as between the FUT2
      genotypes. In addition, the non-secretors had lower species richness than the
      secretors. The soft clustering of microbiota into enterotypes (ET) 1 and 3 showed
      that the non-secretors had a higher probability of belonging to ET1 and the
      secretors to ET3. Our study shows that secretor status and FUT2 polymorphism are
      associated with the composition of human intestinal microbiota, and appears thus
      to be one of the key drivers affecting the individual variation of human
      intestinal microbiota. 

PMID- 24733312
TI  - Supramolecular self-assembly of brominated molecules on a silicon surface.
AB  - Hydrogen and halogen bonds have been associated for the growth of 2D compact
      supramolecular networks on a silicon surface. These interactions have been
      elucidated in a complete monolayer of a 4,4''-dibromo-p-terphenyl (DBT) molecule
      on a Si(111)-B surface by combining scanning tunneling microscopy (STM) and
      density functional theory (DFT) calculations. 

PMID- 24733313
TI  - Regional versus widespread pain in patients with chronic low back pain: it does
      matter!

PMID- 24733314
TI  - Family physicians and electronic communication.

PMID- 24733316
TI  - Beauty of patient-centred care within a cultural context.

PMID- 24733318
TI  - Vitamin B12 doses and the elderly.

PMID- 24733319
TI  - Elaboration on vitamin B12.

PMID- 24733320
TI  - Age of complexity.

PMID- 24733322
TI  - Toxoplasmosis and pregnancy.
AB  - Question Congenital toxoplasmosis is a dangerous fetal infection. Why is routine
      screening for Toxoplasma gondii infection during pregnancy not available for most
      Canadians? Answer Low prevalence of the infection, high cost associated with
      testing, low sensitivity of screening tests, false-positive test results, and
      limitations of treatment effectiveness are all cited as reasons for not routinely
      screening for T gondii infection in Canada. Currently, screening for the
      detection of T gondii is only performed in Nunavik and other parts of northern
      Quebec owing to the high prevalence of infection in this region. Congenital
      toxoplasmosis causes neurologic or ocular disease (leading to blindness), as well
      as cardiac and cerebral anomalies. 

PMID- 24733323
TI  - Early exposure to food and food allergy in children.
AB  - Question I have been under the impression that infants should avoid potential
      allergenic foods such as nuts, cow's milk, and eggs in order to avoid developing
      allergic reactions. What advice should I give parents regarding the introduction
      of food in infancy and the development of food allergy? Answer There is no
      evidence that delaying the introduction of any specific food beyond 6 months of
      age helps to prevent allergy. A recent Canadian Paediatric Society statement
      recommends no delay in the introduction of food in infancy. Recent research also
      appears to suggest that early introduction of potentially allergenic foods (at 4
      to 6 months of age) might actually provide a form of protection and help prevent
      allergy, but more research is needed. 

PMID- 24733321
TI  - Bisphosphonates for treatment of osteoporosis: expected benefits, potential
      harms, and drug holidays.
AB  - OBJECTIVE: To outline the efficacy and risks of bisphosphonate therapy for the
      management of osteoporosis and describe which patients might be eligible for
      bisphosphonate "drug holiday." QUALITY OF EVIDENCE: MEDLINE (PubMed, through
      December 31, 2012) was used to identify relevant publications for inclusion. Most
      of the evidence cited is level II evidence (non-randomized, cohort, and other
      comparisons trials). MAIN MESSAGE: The antifracture efficacy of approved first
      line bisphosphonates has been proven in randomized controlled clinical trials.
      However, with more extensive and prolonged clinical use of bisphosphonates,
      associations have been reported between their administration and the occurrence
      of rare, but serious, adverse events. Osteonecrosis of the jaw and atypical
      subtrochanteric and diaphyseal femur fractures might be related to the use of
      bisphosphonates in osteoporosis, but they are exceedingly rare and they often
      occur with other comorbidities or concomitant medication use. Drug holidays
      should only be considered in low-risk patients and in select patients at moderate
      risk of fracture after 3 to 5 years of therapy. CONCLUSION: When bisphosphonates
      are prescribed to patients at high risk of fracture, their antifracture benefits
      considerably outweigh their potential for harm. For patients taking
      bisphosphonates for 3 to 5 years, reassess the need for ongoing therapy.

PMID- 24733324
TI  - Runner's new diet, his collapse, and his ECG: when a rapid ECG diagnosis can save
      the day.

PMID- 24733325
TI  - Turning over the rocks: role of anticholinergics and benzodiazepines in cognitive
      decline and falls.

PMID- 24733326
TI  - Testing vitamin D levels.

PMID- 24733327
TI  - New therapy for managing moderate to severe chronic obstructive pulmonary
      disease.

PMID- 24733329
TI  - Donald Ingram Rice: 1965-1985: constructing certification in family medicine.

PMID- 24733328
TI  - Socioeconomic composition of low-acuity emergency department users in Ontario.
AB  - OBJECTIVE: To describe the associations between the socioeconomic status of
      emergency department (ED) users and age, sex, and acuity of medical conditions to
      better understand users' common characteristics, and to better meet primary and
      ambulatory health care needs. DESIGN: A retrospective, observational, population
      based analysis. A rigorous proxy of socioeconomic status was applied using census
      based methods to calculate a relative deprivation index. SETTING: Ontario.
      PARTICIPANTS: All Ontario ED visits for the fiscal year April 1, 2008, to March
      31, 2009, from the National Ambulatory Care Reporting System data set. MAIN
      OUTCOME MEASURES: Emergency department visits were ranked into deprivation
      quintiles, and associations between deprivation and age, sex, acuity at triage,
      and association with a primary care physician were investigated. RESULTS: More
      than 25% of ED visits in Ontario were from the most deprived population; almost
      half of those (12.3%) were for conditions of low acuity. Age profiles indicated
      that a large contribution to low-acuity ED visits was made by young adults (aged
      20 to 30 years) from the most deprived population. For the highest-volume ED in
      Ontario, 94 of the 499 ED visits per day were for low-acuity patients from the
      most deprived population. Most of the highest volume EDs in Ontario (more than
      200 ED visits per day) follow this trend. CONCLUSION: Overall input into EDs
      might be reduced by providing accessible and appropriate primary health care
      resources in catchment areas of EDs with high rates of low-acuity ED visits,
      particularly for young adults from the most deprived segment of the population.

PMID- 24733330
TI  - The FitzGeralds: accolades and agony.

PMID- 24733332
TI  - Scholarship for community physicians.

PMID- 24733333
TI  - Getting to usable EMR data.

PMID- 24733334
TI  - Finding the path together.

PMID- 24733337
TI  - The CFPC's relationship with the health care and pharmaceutical industry.

PMID- 24733341
TI  - Medication-related emergency department visits and hospitalizations among older
      adults.
AB  - OBJECTIVE: To identify medications that have a high risk of adverse drug effects
      (ADEs) among seniors, using data from publicly available administrative
      databases. DESIGN: Cross-sectional study using the Discharge Abstracts Database
      (DAD) (which contains data on acute care institutions in all provinces and
      territories except Quebec), the National Ambulatory Care Reporting System (NACRS)
      (which contains data on emergency department [ED] visits in Ontario), and the IMS
      Brogan database Canadian CompuScript. SETTING: Canada. PARTICIPANTS: Adults 65
      years of age and older with diagnostic codes for drugs, medicaments, and biologic
      substances causing adverse effects in therapeutic use. MAIN OUTCOME MEASURES:
      Adverse drug events from 2006 to 2008 associated with hospitalizations and ED
      visits among adults 65 years of age and older were identified by the DAD and the
      NACRS. The medications most frequently prescribed by primary care providers in
      2008 were identified using data from Canadian CompuScript. RESULTS: From 2006 to
      2008, the DAD identified 92 141 ADEs among older adults, and the NACRS identified
      23 845 ADEs among older adults in Ontario EDs, which represented 2.9% of
      inpatients and 0.8% of ED patients (21.5% of whom were admitted to hospital).
      Drugs implicated in the DAD ADEs included anticoagulants (15.4%), antineoplastic
      agents (10.6%), opioids (9.2%), and nonsteroidal anti-inflammatory drugs (6.5%);
      drugs included in the ADEs of ED visits were anti-infective agents (15.9%),
      anticoagulants (14.2%), antineoplastic agents (9.6%), and opioids (7.3%).
      CONCLUSION: Among older adults, the drug classes most often associated with
      causing harm in the hospital setting and occurring out of proportion to the
      frequency prescribed were anticoagulants, opioids, antibiotics, and
      cardiovascular drugs. Thus, these drug classes should be the focus of quality
      improvement efforts in primary care.

PMID- 24733342
TI  - Emergency department use: is frequent use associated with a lack of primary care
      provider?
AB  - OBJECTIVE: To determine if having a primary care provider is an important factor
      in frequency of emergency department (ED) use. DESIGN: Analysis of a central
      computerized health network database. SETTING: Three EDs in southern New
      Brunswick. PARTICIPANTS: All ED visits during 1 calendar year to an urban
      regional hospital (URH), an urban urgent care centre (UCC), and a rural community
      hospital (RCH) were captured. MAIN OUTCOME MEASURES: Patients with and without
      listed primary care providers were compared in terms of number of visits to the
      ED. A logistic regression analysis was used to determine factors predictive of
      frequent attendance. RESULTS: In total, 48 505, 41 004, and 27 900 visits were
      made to the URH, UCC, and RCH, respectively, in 2009. The proportion of patients
      with listed primary care providers was 36.6% for the URH, 37.1% for the UCC, and
      89.4% for the RCH. Among ED patients at all sites, frequent attenders (4 or more
      visits to an ED in 1 year) were significantly more likely (59.6% vs 45.1%, P <
      .001) to have listed primary care providers. Other factors that predicted
      frequent use included attendance at a rural ED, female sex, and older age.
      CONCLUSION: This study characterizes attendance rates for 3 EDs in southern New
      Brunswick. Our findings highlight interesting differences between urban and rural
      ED populations, and suggest that frequent use of the ED might not be related to
      lack of a listed primary care provider.

PMID- 24733343
TI  - Patient satisfaction with access and continuity of care in a multidisciplinary
      academic family medicine clinic.
AB  - OBJECTIVE: To determine patient satisfaction with care provided at a family
      medicine teaching clinic. DESIGN: Mailed survey. SETTING: Victoria Family Medical
      Centre in London, Ont. PARTICIPANTS: Stratified random sample of 600 regular
      patients of the clinic aged 18 years or older; 301 responses were received. MAIN
      OUTCOME MEASURES: Patient satisfaction with overall care, wait times for
      appointments, contact with physicians, and associated demographic factors.
      Logistic regression analysis and analysis were used to determine the significance
      of factors associated with satisfaction. RESULTS: The response rate was 50%.
      Overall, 88% of respondents were fairly, very, or completely satisfied with care.
      Older patients tended to be more satisfied. Patients who were less satisfied had
      longer wait times for appointments (P < .001) and reduced continuity with
      specific doctors (P = .004). More satisfied patients also felt connected through
      other members of the health care team. CONCLUSION: Patients were generally
      satisfied with the care provided at the family medicine teaching clinic. Older
      patients tended to be more satisfied than younger patients. Points of
      dissatisfaction were related to wait times for appointments and continuity with
      patients' usual doctors. These findings support the adoption of practices that
      reduce wait times and facilitate continuity with patients' usual doctors and
      other regular members of the health care team.

PMID- 24733348
TI  - Serum free immunoglobulin light chain evaluation as a marker of impact from
      intraclonal heterogeneity on myeloma outcome.
AB  - Intraclonal heterogeneity was recently described in multiple myeloma (MM), but
      its full impact on disease progression and relapse has not been entirely
      explored. The immunoglobulin type produced by myeloma cells provides an excellent
      marker to follow changes in clonal substructure over time. We have prospectively
      evaluated serial paraprotein and serum free light chain (FLC) measurements and
      found that 258 of 520 and 54 of 520 patients who presented with a whole
      paraprotein relapsed with paraprotein only (PO) and "FLC escape," respectively.
      The median overall survival of PO patients was longer, when compared with
      patients whose relapse manifested as an increase in FLC both alone and with a
      whole paraprotein, as a result of a significantly shorter survival from relapse
      of the latter groups. These observations fit a model in which 1 clone is able to
      produce a complete antibody, whereas the other secretes only FLC; the type of
      relapse represents the outgrowth of different clones, some of which are more
      resistant to therapy. To our knowledge, this is the largest series describing
      patients who have relapsed with FLC escape and highlights the importance of
      monitoring FLC when there is a suspicion of clinical relapse. This study was
      registered at www.isrctn.org as ISRCTN68454111. 

PMID- 24733347
TI  - An agomir of miR-144-3p accelerates plaque formation through impairing reverse
      cholesterol transport and promoting pro-inflammatory cytokine production.
AB  - AIMS: ATP-binding cassette transporter A1 (ABCA1) mediates the efflux of
      cholesterol and phospholipids to lipid-poor apolipoproteins, which then form
      nascent HDL, a key step in the mechanism of reverse cholesterol transport (RCT).
      While a series of microRNAs (miRNAs) have been identified as potent post
      transcriptional regulators of lipid metabolism, their effects on ABCA1 function
      and associated mechanisms remain unclear. METHODS AND RESULTS: ABCA1 was
      identified as a potential target of miR-144-3p, based on the results of
      bioinformatic analysis and the luciferase reporter assay, and downregulated after
      transfection of cells with miR-144-3p mimics, as observed with real-time PCR and
      western blot. Moreover, miR-144-3p mimics (agomir) enhanced the expression of
      inflammatory factors, including IL-1beta, IL-6 and TNF-alpha, in vivo and in
      vitro, inhibited cholesterol efflux in THP-1 macrophage-derived foam cells,
      decreased HDL-C circulation and impaired RCT in vivo, resulting in accelerated
      pathological progression of atherosclerosis in apoE-/- mice. Clinical studies
      additionally revealed a positive correlation of circulating miR-144-3p with serum
      CK, CK-MB, LDH and AST in subjects with AMI. CONCLUSIONS: Our findings clearly
      indicate that miR-144-3p is essential for the regulation of cholesterol
      homeostasis and inflammatory reactions, supporting its utility as a potential
      therapeutic target of atherosclerosis and a promising diagnostic biomarker of
      AMI.

PMID- 24733349
TI  - Validity and reliability question 8 of the Paffenbarger Physical Activity
      Questionnaire among healthy adults.
AB  - BACKGROUND: Little information exists regarding the psychometric properties of
      question 8 (Q8) of the Paffenbarger Physical Activity Questionnaire (PPAQ) to
      assess exercise. Thus, we conducted 2 studies to assess the validity and test
      retest reliability of Q8 among adults. METHODS: Study 1 participants (n = 419)
      were 44.1 +/- 16.1 years of age. Validity was determined by comparing self
      reported hr.d-1 in sedentary, light, moderate, and vigorous intensity physical
      activity (PA) and MET-hr.wk-1 on Q8 at baseline to accelerometer and
      health/fitness measurements using Spearman rank-order correlations. Study 2
      participants (n = 217) were 44.7 +/- 16.3 years of age and completed Q8 at
      baseline, 3 months, and 6 months. Test-retest reliability was determined using
      repeated measures analysis of covariance, intraclass correlations (ICCs), and
      standard error of the measurement (SEM). RESULTS: Q8 displayed good criterion
      validity compared with accelerometer measurements (r = .102 to .200, P < .05) and
      predictive validity compared with health/fitness measurements (r = -.272 to .203,
      P < .05). No differences were observed in self-reported hr.d-1 in any of the PA
      categories at baseline, 3 months, and 6 months (ICC: 0.49 to 0.68; SEM: 1.0 to
      2.0; P > .05), indicating good reliability. CONCLUSION: Q8 demonstrates adequate
      criterion validity, acceptable predictive validity, and satisfactory test-retest
      reliability and can be used in conjunction with other components of the PPAQ to
      provide a complete representation of exercise.

PMID- 24733350
TI  - The complex problem of childhood obesity.

PMID- 24733351
TI  - The regulatory sciences for stem cell-based medicinal products.
AB  - Over the past few years, several new achievements have been made from stem cell
      studies, many of which have moved up from preclinical stages to early, or from
      early to middle or late, stages thanks to relatively safe profile and preliminary
      evidence of effectiveness. Moreover, some stem cell-based products have been
      approved for marketing by different national regulatory authorities. However,
      many critical issues associated mainly with incomplete understanding of stem cell
      biology and the relevant risk factors, and lack of effective regulations still
      exist and need to be urgently addressed, especially in countries where
      establishment of appropriate regulatory system just commenced. More relevantly,
      the stem cell regulatory sciences need to be established or improved to more
      effectively evaluate quality, safety and efficacy of stem cell products, and for
      building up the appropriate regulatory framework. In this review, we summarize
      some new achievements in stem cell studies, especially the preclinical and
      clinical studies, the existing regulations, and the associated challenges, and we
      then propose some considerations for improving stem cell regulatory sciences with
      a goal of promoting the steadfast growth of the well-regulated stem cell
      therapies abreast of evolvement of stem cell sciences and technologies. 

PMID- 24733352
TI  - Chymase mediates injury and mitochondrial damage in cardiomyocytes during acute
      ischemia/reperfusion in the dog.
AB  - Cardiac ischemia and reperfusion (I/R) injury occurs because the acute increase
      in oxidative/inflammatory stress during reperfusion culminates in the death of
      cardiomyocytes. Currently, there is no drug utilized clinically that attenuates
      I/R injury in patients. Previous studies have demonstrated degranulation of mast
      cell contents into the interstitium after I/R. Using a dog model of I/R, we
      tested the role of chymase, a mast cell protease, in cardiomyocyte injury using a
      specific oral chymase inhibitor (CI). 15 adult mongrel dogs had left anterior
      descending artery occlusion for 60 min and reperfusion for 100 minutes. 9 dogs
      received vehicle and 6 were pretreated with a specific CI. In vivo cardiac
      microdialysis demonstrated a 3-fold increase in interstitial fluid chymase
      activity in I/R region that was significantly decreased by CI. CI pretreatment
      significantly attenuated loss of laminin, focal adhesion complex disruption, and
      release of troponin I into the circulation. Microarray analysis identified an I/R
      induced 17-fold increase in nuclear receptor subfamily 4A1 (NR4A1) and
      significantly decreased by CI. NR4A1 normally resides in the nucleus but can
      induce cell death on migration to the cytoplasm. I/R caused significant increase
      in NR4A1 protein expression and cytoplasmic translocation, and mitochondrial
      degradation, which were decreased by CI. Immunohistochemistry also revealed a
      high concentration of chymase within cardiomyocytes after I/R. In vitro, chymase
      added to culture HL-1 cardiomyocytes entered the cytoplasm and nucleus in a
      dynamin-dependent fashion, and promoted cytoplasmic translocation of NR4A1
      protein. shRNA knockdown of NR4A1 on pre-treatment of HL-1 cells with CI
      significantly decreased chymase-induced cell death and mitochondrial damage.
      These results suggest that the beneficial effects of an orally active CI during
      I/R are mediated in the cardiac interstitium as well as within the cardiomyocyte
      due to a heretofore-unrecognized chymase entry into cardiomyocytes. 

PMID- 24733353
TI  - A paper electrode integrated lateral flow immunosensor for quantitative analysis
      of oxidative stress induced DNA damage.
AB  - A novel device combining electrochemical and colorimetric detection is developed
      for the rapid measurement of 8-hydroxy-2'-deoxyguanosine (8-OHdG), a DNA
      oxidative damage biomarker. The device takes advantage of the speed and low cost
      of the conventional strip test as well as the high reliability and accuracy of
      the electrochemical assay. Competitive immunoreactions were performed on the
      lateral flow strip, and the captured 8-OHdG on the control line was determined by
      chronoamperometric measurement with carbon nanotube paper as the working
      electrode. At the same time, the color intensity of the test line was measured by
      a scanner and analyzed by the ImageJ software. The device was able to detect 8
      OHdG concentrations in PBS as low as 2.07 ng mL(-1) by the colorimetric method
      and 3.11 ng mL(-1) by the electrochemical method. Furthermore, the device was
      successfully utilized to detect 8-OHdG in urine with a detection limit of 5.76 ng
      mL(-1) (colorimetric method) and 8.85 ng mL(-1) (electrochemical method),
      respectively. In conclusion, the integrated device with dual detection methods
      can provide a rapid, visual, quantitative and feasible detection method for 8
      OHdG. The integration of these two methods holds two major advantages over tests
      based on a single method. Firstly, it can provide double confidence on the same
      assay. Secondly, by involving two methods that differ in principle, the
      integration could potentially avoid false results coming from one method. In
      addition, these methods do not require expensive equipment or trained personnel,
      making it suitable for use as a simple, economical, portable field kit for on
      site monitoring of 8-OHdG in a variety of clinical settings. 

PMID- 24733355
TI  - Elevating the quality of disability and rehabilitation research: mandatory use of
      the reporting guidelines.

PMID- 24733354
TI  - Reduction of inappropriate benzodiazepine prescriptions among older adults
      through direct patient education: the EMPOWER cluster randomized trial.
AB  - IMPORTANCE: The American Board of Internal Medicine Foundation Choosing Wisely
      Campaign recommends against the use of benzodiazepine drugs for adults 65 years
      and older. The effect of direct patient education to catalyze collaborative care
      for reducing inappropriate prescriptions remains unknown. OBJECTIVE: To compare
      the effect of a direct-to-consumer educational intervention against usual care on
      benzodiazepine therapy discontinuation in community-dwelling older adults.
      DESIGN, SETTING, AND PARTICIPANTS: Cluster randomized trial (EMPOWER [Eliminating
      Medications Through Patient Ownership of End Results] study [2010-2012, 6-month
      follow-up]). Community pharmacies were randomly allocated to the intervention or
      control arm in nonstratified, blocked groups of 4. Participants (303 long-term
      users of benzodiazepine medication aged 65-95 years, recruited from 30 community
      pharmacies) were screened and enrolled prior to randomization: 15 pharmacies
      randomized to the educational intervention included 148 participants and 15
      pharmacies randomized to the "wait list" control included 155 participants.
      Participants, physicians, pharmacists, and evaluators were blinded to outcome
      assessment. INTERVENTIONS: The active arm received a deprescribing patient
      empowerment intervention describing the risks of benzodiazepine use and a
      stepwise tapering protocol. The control arm received usual care. MAIN OUTCOMES
      AND MEASURES: Benzodiazepine therapy discontinuation at 6 months after
      randomization, ascertained by pharmacy medication renewal profiles. RESULTS: A
      total of 261 participants (86%) completed the 6-month follow-up. Of the
      recipients in the intervention group, 62% initiated conversation about
      benzodiazepine therapy cessation with a physician and/or pharmacist. At 6 months,
      27% of the intervention group had discontinued benzodiazepine use compared with
      5% of the control group (risk difference, 23% [95% CI, 14%-32%]; intracluster
      correlation, 0.008; number needed to treat, 4). Dose reduction occurred in an
      additional 11% (95% CI, 6%-16%). In multivariate subanalyses, age greater than 80
      years, sex, duration of use, indication for use, dose, previous attempt to taper,
      and concomitant polypharmacy (10 drugs or more per day) did not have a
      significant interaction effect with benzodiazepine therapy discontinuation.
      CONCLUSIONS AND RELEVANCE: Direct-to-consumer education effectively elicits
      shared decision making around the overuse of medications that increase the risk
      of harm in older adults. TRIAL REGISTRATION: clinicaltrials.gov Identifier:
      NCT01148186.

PMID- 24733359
TI  - Solution properties and electrospinning of phosphonium gemini surfactants.
AB  - Bis(diphenylphosphino)alkanes quantitatively react with excess 1-bromododecane to
      prepare novel phosphonium gemini surfactants with spacer lengths ranging from 2
      to 4 methylenes (12-2/3/4-12P). Dodecyltriphenylphosphonium bromide (DTPP), a
      monomeric surfactant analog, was readily water soluble, however, in sharp
      contrast, phosphonium gemini surfactants were poorly soluble in water due to two
      hydrophobic tails and relatively hydrophobic cationic head groups containing
      phenyl substituents. Isothermal titration calorimetry did not reveal a measurable
      critical micelle concentration for the 12-2-12P phosphonium gemini surfactant in
      water at 25  degrees C. Subsequent studies in 50/50 v/v water-methanol at 25 
      degrees C showed a CMC of 1.0 mM for 12-2-12P. All phosphonium gemini surfactants
      effectively complexed nucleic acids, but failed to deliver nucleic acids in vitro
      to HeLa cells. The solution behavior of phosphonium gemini surfactants was
      investigated in chloroform, which is an organic solvent where reverse micellar
      structures are favored. Solution rheology in chloroform explored the solution
      behavior of the phosphonium gemini surfactants compared to DTPP. The 12-2-12P and
      12-3-12P gemini surfactants were successfully electrospun from chloroform to
      generate uniform fibers while 12-4-12P gemini surfactant and DTPP only
      electrosprayed to form droplets. 

PMID- 24733356
TI  - Renal involvement in non-Hodgkin lymphoma: proven by renal biopsy.
AB  - AIMS: To determine the spectrum of renal lesions in patients with kidney
      involvement in non-Hodgkin's lymphoma (NHL) by renal biopsy. METHODS: The
      clinical features and histological findings at the time of the renal biopsy were
      assessed for each patient. RESULTS: We identified 20 patients with NHL and renal
      involvement, and the diagnosis of NHL was established following the kidney biopsy
      in 18 (90%) patients. The types of NHL include the following: chronic lymphocytic
      leukemia/small lymphocytic lymphoma (n = 8), diffuse large B-cell lymphoma (n =
      4), T/NK cell lymphoma (n = 3), lymphoplasmacytic lymphoma (n = 2), cutaneous T
      cell lymphoma (n = 1), mucosa-associated lymphoid tissue lymphoma (n = 1) and
      mantle cell lymphoma (n = 1). All presented with proteinuria, and 15 patients had
      impaired renal function. The pathological findings included (1)
      membranoproliferative glomerulonephritis-like pattern in seven patients; (2)
      crescent glomerulonephritis in four; (3) minimal-change disease in three, and
      glomeruli without specific pathological abnormalities in three; (4)
      intraglomerular large B-cell lymphoma in one; (5) intracapillary monoclonal IgM
      deposits in one; (6) primary diffuse large B-cell lymphoma of the kidneys in one;
      and (7) lymphoma infiltration of the kidney in eight patients. CONCLUSION: A wide
      spectrum of renal lesions can be observed in patients with NHL, and NHL may be
      first proven by renal biopsies for evaluation of kidney injury or proteinuria.
      Renal biopsy is necessary to establish the underlying cause of renal involvement
      in NHL.

PMID- 24733360
TI  - Role of Rip2 in development of tumor-infiltrating MDSCs and bladder cancer
      metastasis.
AB  - Tumor invasion and metastases represent a complex series of molecular events that
      portends a poor prognosis. The contribution of inflammatory pathways mediating
      this process is not well understood. Nod-like receptors (NLRs) of innate immunity
      function as intracellular sensors of pathogen motifs and danger molecules. We
      propose a role of NLRs in tumor surveillance and in programming tumor
      infiltrating lymphocytes (TILs). In this study, we examined the downstream
      serine/threonine and tyrosine kinase Rip2 in a murine model of bladder cancer. In
      Rip2-deficient C57Bl6 mice, larger orthotopic MB49 tumors developed with more
      numerous and higher incidence of metastases compared to wild-type controls. As
      such, increased tumor infiltration of CD11b+ Gr1hi myeloid-derived suppressor
      cells (MDSCs) with concomitant decrease in T cells and NK cells were observed in
      Rip2-deficient tumor bearing animals using orthotopic and subcutaneous tumor
      models. Rip2-deficient tumors showed enhanced epithelial-to-mesenchymal
      transition, with elevated expression of zeb1, zeb2, twist, and snail in the tumor
      microenvironment. We found that the absence of Rip2 plays an intrinsic role in
      fostering the development of granulocytic MDSCs by an autocrine and paracrine
      effect of granulocytic colony stimulating factor (G-CSF) expression. Our findings
      suggest that NLR pathways may be a novel modality to program TILs and influence
      tumor metastases.

PMID- 24733362
TI  - Non-traumatic hypertrophic callus of the fibula mimicking osteosarcoma in
      osteogenesis imperfecta type V: a case report.
AB  - We report a case of hyperplastic callus mimicking osteosarcoma in the fibula of a
      patient with osteogenesis imperfecta type V. Among the various imaging
      modalities, computed tomography was the most useful in distinguishing this rare
      process from a malignant entity. In addition, simple radiographs demonstrated the
      presence of characteristic "zebra lines", a manifestation of cyclic
      bisphosphonate therapy during childhood. 

PMID- 24733361
TI  - Filial attachment and its disruption: insights from the guinea pig.
AB  - Guinea pigs are precocial rodents that show evidence of a selective attachment to
      the mother who, in turn, exhibits little active maternal care. Effects of
      separation in guinea pigs are, therefore, more likely to reflect the disruption
      of attachment than the removal of, or alterations in, patterns of maternal care.
      Here, effects in guinea pigs of the presence or absence of the mother on
      psychobiological endpoints and of maternal separation on depressive-like behavior
      are reviewed. It is argued that results with guinea pigs often align more closely
      with those of nonhuman primates than those of laboratory rats and mice, and that
      the guinea pig offers a valuable translational model for studies of the
      consequences of attachment and its disruption.

PMID- 24733363
TI  - Incidental encoding of enclosure geometry does not require visual input: evidence
      from blindfolded adults.
AB  - Although spatial orientation with respect to the geometric properties of an
      environment appears to be an ability shared across various species, debate
      remains concerning potential similarities and differences with respect to the
      underlying mechanism(s). One prominent theoretical account of orientation with
      respect to the environment suggests that participants match visual memories to
      their current visual perception and navigate to reduce the discrepancy between
      the two. We tested whether visual input was necessary to incidentally encode the
      geometric properties of an environment, by training disoriented and blindfolded
      adult participants to search by touch for a target object hidden in one of four
      locations, marked by distinctive textural cues, located in the corners of a
      rectangular enclosure. Following training, we removed the distinctive textural
      cues and probed the extent to which the participants had learned the geometry of
      the enclosure. Even in the absence of vision and unique textural cues, search
      behavior was consistent with evidence for the encoding of enclosure geometry. A
      follow-up experiment in which participants were trained in a rectangular
      enclosure but were tested in a square enclosure provided converging evidence that
      search behavior was influenced by the geometric properties of the enclosure.
      Collectively, these results suggest that even in the absence of vision,
      participants incidentally encoded the geometric properties of the enclosure,
      indicating that visual input is not required to encode the geometric properties
      of an environment.

PMID- 24733366
TI  - High temperature and salinity enhance soil nitrogen mineralization in a tidal
      freshwater marsh.
AB  - Soil nitrogen (N) mineralization in wetlands is sensitive to various
      environmental factors. To compare the effects of salinity and temperature on N
      mineralization, wetland soils from a tidal freshwater marsh locating in the
      Yellow River Delta was incubated over a 48-d anaerobic incubation period under
      four salinity concentrations (0, 10, 20 and 350/00) and four temperature levels
      (10, 20, 30 and 40 degrees C). The results suggested that accumulated ammonium
      nitrogen (NH4+-N) increased with increasing incubation time under all salinity
      concentrations. Higher temperatures and salinities significantly enhanced soil N
      mineralization except for a short-term (~10 days) inhibiting effect found under
      350/00 salinity. The incubation time, temperature, salinity and their
      interactions exhibited significant effects on N mineralization (P<0.001) except
      the interactive effect of salinity and temperature (P>0.05), while temperature
      exhibited the greatest effect (P<0.001). Meanwhile, N mineralization processes
      were simulated using both an effective accumulated temperature model and a one
      pool model. Both models fit well with the simulation of soil N mineralization
      process in the coastal freshwater wetlands under a range of 30 to 40 degrees C
      (R2 = 0.88-0.99, P<0.01). Our results indicated that an enhanced NH4+-N release
      with increasing temperature and salinity deriving from the projected global
      warming could have profound effects on nutrient cycling in coastal wetland
      ecosystems. 

PMID- 24733364
TI  - Is gestational hypertension protective against perinatal mortality in twin
      pregnancies?
AB  - BACKGROUND: Pregnancy-induced or gestational hypertension is a common pregnancy
      complication. Paradoxically, gestational hypertension has been associated with a
      protective effect against perinatal mortality in twin pregnancies in analytic
      models (logistic regression) without accounting for survival time. Whether this
      effect is real remains uncertain. This study aimed to validate the impact of
      gestational hypertension on perinatal mortality in twin pregnancies using a
      survival analysis approach. METHODS: This was a retrospective cohort study of
      278,821 twin pregnancies, using the U.S. 1995-2000 matched multiple birth dataset
      (the largest dataset available for multiple births). Cox proportional hazard
      models were applied to estimate the adjusted hazard ratios (aHR) of perinatal
      death (stillbirth and neonatal death) comparing gestational hypertensive vs. non
      hypertensive pregnancies controlling for maternal characteristics and twin
      cluster-level dependence. RESULTS: Comparing births in gestational hypertensive
      vs. non-hypertensive twin pregnancies, perinatal mortality rates were
      significantly lower (1.20% vs. 3.38%), so were neonatal mortality (0.72% vs.
      2.30%) and stillbirth (0.48% vs. 1.10%) rates. The aHRs (95% confidence
      intervals) were 0.34 (0.31-0.38) for perinatal death, 0.31 (0.27-0.34) for
      neonatal death, and 0.45 (0.38-0.53) for stillbirth, respectively. The protective
      effect of gestational hypertension against perinatal death became weaker over
      advancing gestational age; the aHRs in very preterm (<32 weeks), mild preterm (32
      36 weeks) and term (37+ weeks) births were 0.29, 0.48 and 0.76, respectively. The
      largest risk reductions in neonatal mortality were observed for infections and
      immaturity-related conditions. CONCLUSIONS: Gestational hypertension appears to
      be beneficial for fetal survival in twin pregnancies, especially in those ending
      more prematurely or for deaths due to infections and immaturity-related
      conditions. Prospective studies are required to rule out the possibility of
      unmeasured confounders.

PMID- 24733365
TI  - Odds of Getting Adequate Physical Activity by Dog Walking.
AB  - BACKGROUND: We aimed to determine the likelihood that adult dog owners who walk
      their dogs will achieve a healthy level of moderate-intensity (MI) physical
      activity (PA), defined as at least 150 mins/wk. METHODS: We conducted a
      systematic search of 6 databases with data from 1990-2012 on dog owners' PA, to
      identify those who achieved MIPA. To compare dog-walkers' performance with non
      dog walkers, we used a random effects model to estimate the unadjusted odds ratio
      (OR) and corresponding 95% confidence interval (CI). RESULTS: We retrieved 9
      studies that met our inclusion criterion and allowed OR calculations. These
      yielded data on 6980 dog owners aged 18 to 81 years (41% men). Among them, 4463
      (63.9%) walked their dogs. Based on total weekly PA, 2710 (60.7%) dog walkers,
      and 950 (37.7%) non-dog walkers achieved at least MIPA. The estimated OR was 2.74
      (95% CI 2.09-3.60). CONCLUSION: Across 9 published studies, almost 2 in 3 dog
      owners reported walking their dogs, and the walkers are more than 2.5 times more
      likely to achieve at least MIPA. These findings suggest that dog walking may be a
      viable strategy for dog owners to help achieve levels of PA that may enhance
      their health.

PMID- 24733367
TI  - High-sensitivity cardiac troponin I assay to screen for acute rejection in
      patients with heart transplant.
AB  - BACKGROUND: A noninvasive biomarker that could accurately diagnose acute
      rejection (AR) in heart transplant recipients could obviate the need for
      surveillance endomyocardial biopsies. We assessed the performance metrics of a
      novel high-sensitivity cardiac troponin I (cTnI) assay for this purpose. METHODS
      AND RESULTS: Stored serum samples were retrospectively matched to endomyocardial
      biopsies in 98 cardiac transplant recipients, who survived >=3 months after
      transplant. AR was defined as International Society for Heart and Lung
      Transplantation grade 2R or higher cellular rejection, acellular rejection, or
      allograft dysfunction of uncertain pathogenesis, leading to treatment for
      presumed rejection. cTnI was measured with a high-sensitivity assay (Abbott
      Diagnostics, Abbott Park, IL). Cross-sectional analyses determined the
      association of cTnI concentrations with rejection and International Society for
      Heart and Lung Transplantation grade and the performance metrics of cTnI for the
      detection of AR. Among 98 subjects, 37% had >=1 rejection episode. cTnI was
      measured in 418 serum samples, including 35 paired to a rejection episode. cTnI
      concentrations were significantly higher in rejection versus nonrejection samples
      (median, 57.1 versus 10.2 ng/L; P<0.0001) and increased in a graded manner with
      higher biopsy scores (P(trend)<0.0001). The c-statistic to discriminate AR was
      0.82 (95% confidence interval, 0.76-0.88). Using a cut point of 15 ng/L,
      sensitivity was 94%, specificity 60%, positive predictive value 18%, and negative
      predictive value 99%. CONCLUSIONS: A high-sensitivity cTnI assay seems useful to
      rule out AR in cardiac transplant recipients. If validated in prospective
      studies, a strategy of serial monitoring with a high-sensitivity cTnI assay may
      offer a low-cost noninvasive strategy for rejection surveillance.

PMID- 24733368
TI  - Splenic injury complicating ERCP.
AB  - Endoscopic retrograde cholangiopancreatography (ERCP) is an invasive procedure
      which carries a complication rate of 5-10%. Splenic injury is a very rare and
      potentially lethal complication following ERCP. We report a case of a 64-year-old
      man with a mass at the pancreatic head and obstructive jaundice, who sustained a
      splenic injury following ERCP. Six hours after the procedure, the patient
      presented with epigastric pain and hypotension. The abdominal CT scan revealed
      splenic hematoma. He was offered surgical treatment. Splenectomy was performed
      with enterogastrostomy.

PMID- 24733369
TI  - A Web-based, educational, quality-of-life intervention for patients with a
      chronic skin disease: feasibility and acceptance in routine dermatological
      practice.
AB  - Chronic skin diseases have a negative impact on patients' health-related quality
      of life (HRQoL). Patient education might contribute to HRQoL improvement. We
      developed a web-based, educational, HRQoL intervention for patients with a
      chronic skin disease. We aimed to assess 1) the feasibility of implementing the
      intervention in routine dermatological practice and patients' daily life, and 2)
      the acceptance of the intervention by health care providers and patients.
      Additionally, we aimed to create a patient user profile. We conducted an
      observational pilot study at 6 dermatological centres, including 105 outpatients.
      Implementation in routine practice was feasible and acceptable to health care
      providers. However, implementation in patients' daily life was found not to be
      entirely feasible. Perceived relevance by patients was low, though patients rated
      the intervention as convenient and attractive. No univocal user profile was
      found. Suggestions for improvements of the intervention, e.g. tailoring and
      adding blended learning components, are discussed. 

PMID- 24733370
TI  - Chemical exchange saturation transfer (CEST): an efficient tool for detecting
      molecular information on proteins' behaviour.
AB  - A versatile method for assessing protein properties via magnetic resonance
      imaging (MRI) through chemical exchange saturation transfer (CEST) modality is
      described. The observed CEST signal changes allow monitoring of protein
      aggregation processes, protein folding/unfolding steps and interaction with lipid
      membranes. 

PMID- 24733371
TI  - Just one more "noninvasive" test....

PMID- 24733372
TI  - Antibiotic prophylaxis in bariatric surgery with continuous infusion of
      cefazolin: determination of concentration in adipose tissue.
AB  - BACKGROUND: The aim of this study was to evaluate the concentration of cefazolin
      in adipose tissue of patients undergoing bariatric surgery. METHODS: Eighteen
      patients undergoing bariatric surgery were evaluated during the period from
      October 2011 to May 2012. All patients had a dosage schedule of antibiotic
      prophylaxis with cefazolin administered as follows: first, 2 g in anesthetic
      induction, followed by continuous infusion of 1 g diluted in 250 ml of saline
      solution. Adipose samples, collected soon after the incision (initial) and before
      the skin synthesis (final), were analyzed using reverse phase high-pressure
      liquid chromatography. The level of significance adopted was 5 %. RESULTS: The
      cefazolin concentration in the adipose tissue samples at the beginning of surgery
      was an average of 6.66 +/- 2.56 ug/ml. The mean concentration before the skin
      synthesis was 7.93 +/- 2.54 ug/ml. Patients with BMI < 40 kg/m(2) had higher
      initial and final sample concentrations of cefazolin than patients with BMI >= 40
      kg/m(2). There was no surgical site infection (SSI) in any of the patients.
      CONCLUSIONS: In bariatric surgeries, addition of a 1 g increase of cefazolin,
      administered through continuous intravenous infusion, to the currently
      recommended dose of 2 g administered in anesthetic induction provided a
      concentration in the adipose tissue above the minimum inhibitory concentration
      (MIC) of the main causal agents of SSI. An inverse correlation between BMI and
      concentration of cefazolin in adipose tissue was observed.

PMID- 24733373
TI  - S(N)1-S(N)2 and S(N)2-S(N)3 mechanistic changes revealed by transition states of
      the hydrolyses of benzyl chlorides and benzenesulfonyl chlorides.
AB  - Hydrolysis reactions of benzyl chlorides and benzenesulfonyl chlorides were
      theoretically investigated with the density functional theory method, where the
      water molecules are explicitly considered. For the hydrolysis of benzyl chlorides
      (para-Z-C6H4-CH2-Cl), the number of water molecules (n) slightly influences the
      transition-state (TS) structure. However, the para-substituent (Z) of the phenyl
      group significantly changes the reaction process from the stepwise (S(N)1) to the
      concerted (S(N)2) pathway when it changes from the typical electron-donating
      group (EDG) to the typical electron-withdrawing one (EWG). The EDG stabilizes the
      carbocation (MeO-C6H4-CH2(+)), which in turn makes the S(N)1 mechanism more
      favorable and vice versa. For the hydrolysis of benzenesulfonyl chlorides (para-Z
      C6H4-SO2-Cl), both the Z group and n influence the TS structure. For the
      combination of the large n value (n > 9) and EDG, the S(N)2 mechanism was
      preferred. Conversely, for the combination of the small n value and EWG, the
      S(N)3 one was more favorable.

PMID- 24733375
TI  - Why good placements matter: Pre-placement and placement risk factors associated
      with mental health disorders in pre-school children in foster care.
AB  - Pre-school children placed in local authority care show elevated rates of mental
      health disorders when compared to the general population. This study investigated
      risk factors for mental health disorders relating to the period prior to entering
      care and while in care. A representative sample of 43 children in care aged 0-72
      months in an inner London borough underwent comprehensive multidimensional
      assessments. Presence of emotional, behavioural, attachment and adaptive
      disorders was ascertained. Exposure to two pre-placement risk factors and six
      placement risk factors was compared between children with and without a disorder.
      A total of 26 children (60.5%) had at least one mental health disorder. The two
      pre-placement risk factors, multiple types of maltreatment and entry into care
      after the age of 6 months, were both significantly associated with mental health
      disorders. The three placement risk factors of sudden placement moves, multiple
      placement moves and child-carer alienation showed a significant association with
      mental health disorders. There was a strong correlation between the number of
      risk factors and the number of co-morbid mental health disorders per child (r =
      .67, p < .001). In conclusion, this study identified five modifiable risk factors
      related to the quality of safeguarding and fostering services which showed a
      significant association with pre-school mental health. 

PMID- 24733376
TI  - Separating 'emotion' from 'the science': Exploring the perceived value of
      information for parents and families of children with autistic spectrum disorder.
AB  - Autistic spectrum disorder (ASD) is a life-long condition. In recent years, there
      has been a rise in the number of children diagnosed with ASD and a greater
      recognition that parents need clear, accessible information communicated through
      different modalities. The objective of this research was to explore the views of
      stakeholders regarding their information needs, current information modalities
      and the perceived barriers and complexities of information. Three focus groups
      with the same stakeholders were conducted with a range of individuals from a
      variety of backgrounds, all of whom had a personal and/or professional interest
      in ASD. The same stakeholders were included in all three groups to promote depth
      of analysis and to facilitate rapport. All focus groups were audio-recorded,
      transcribed and analysed using thematic analysis. Three main issues were
      identified, including (1) the value of particular information sources; (2) the
      vulnerability of families and (3) the need for validated evidence. It was
      concluded, therefore, that information should be available through a multitude of
      modalities, accounting for the educational ability and economic status of
      families. The information should also be communicated in an accessible style,
      should be presented as trustworthy and clinical professionals may play a key role
      in translating information. Such information also needs to account for practical
      problems inherent to having a child with ASD, including time constraints and
      fatigue. 

PMID- 24733377
TI  - Two-stage, in silico deconvolution of the lymphocyte compartment of the
      peripheral whole blood transcriptome in the context of acute kidney allograft
      rejection.
AB  - Acute rejection is a major complication of solid organ transplantation that
      prevents the long-term assimilation of the allograft. Various populations of
      lymphocytes are principal mediators of this process, infiltrating graft tissues
      and driving cell-mediated cytotoxicity. Understanding the lymphocyte-specific
      biology associated with rejection is therefore critical. Measuring genome-wide
      changes in transcript abundance in peripheral whole blood cells can deliver a
      comprehensive view of the status of the immune system. The heterogeneous nature
      of the tissue significantly affects the sensitivity and interpretability of
      traditional analyses, however. Experimental separation of cell types is an
      obvious solution, but is often impractical and, more worrying, may affect
      expression, leading to spurious results. Statistical deconvolution of the cell
      type-specific signal is an attractive alternative, but existing approaches still
      present some challenges, particularly in a clinical research setting. Obtaining
      time-matched sample composition to biologically interesting, phenotypically
      homogeneous cell sub-populations is costly and adds significant complexity to
      study design. We used a two-stage, in silico deconvolution approach that first
      predicts sample composition to biologically meaningful and homogeneous leukocyte
      sub-populations, and then performs cell type-specific differential expression
      analysis in these same sub-populations, from peripheral whole blood expression
      data. We applied this approach to a peripheral whole blood expression study of
      kidney allograft rejection. The patterns of differential composition uncovered
      are consistent with previous studies carried out using flow cytometry and provide
      a relevant biological context when interpreting cell type-specific differential
      expression results. We identified cell type-specific differential expression in a
      variety of leukocyte sub-populations at the time of rejection. The tissue
      specificity of these differentially expressed probe-set lists is consistent with
      the originating tissue and their functional enrichment consistent with allograft
      rejection. Finally, we demonstrate that the strategy described here can be used
      to derive useful hypotheses by validating a cell type-specific ratio in an
      independent cohort using the nanoString nCounter assay. 

PMID- 24733379
TI  - Transcriptional control of regulatory T-cell differentiation.
AB  - Regulatory T (Treg) cells are essential for maintaining peripheral tolerance and
      for limiting excessive inflammatory responses under various conditions. The
      lineage-specific transcription factor Foxp3 has a critical role in Treg-cell
      biology. Foxp3 forms large protein complexes and cooperates with environmentally
      induced transcription factors to shape the Treg-cell transcriptional program.
      Here, we discuss mechanisms of gene regulation that underlie Treg-cell
      differentiation and function with an emphasis on studies from our laboratory. 

PMID- 24733378
TI  - Intermolecular beta-strand networks avoid hub residues and favor low
      interconnectedness: a potential protection mechanism against chain dissociation
      upon mutation.
AB  - Altogether few protein oligomers undergo a conformational transition to a state
      that impairs their function and leads to diseases. But when it happens, the
      consequences are not harmless and the so-called conformational diseases pose
      serious public health problems. Notorious examples are the Alzheimer's disease
      and some cancers associated with a conformational change of the amyloid precursor
      protein (APP) and of the p53 tumor suppressor, respectively. The transition is
      linked with the propensity of beta-strands to aggregate into amyloid fibers.
      Nevertheless, a huge number of protein oligomers associate chains via beta-strand
      interactions (intermolecular beta-strand interface) without ever evolving into
      fibers. We analyzed the layout of 1048 intermolecular beta-strand interfaces
      looking for features that could provide the beta-strands resistance to
      conformational transitions. The interfaces were reconstructed as networks with
      the residues as the nodes and the interactions between residues as the links. The
      networks followed an exponential decay degree distribution, implying an absence
      of hubs and nodes with few links. Such layout provides robustness to changes. Few
      links per nodes do not restrict the choices of amino acids capable of making an
      interface and maintain high sequence plasticity. Few links reduce the "bonding"
      cost of making an interface. Finally, few links moderate the vulnerability to
      amino acid mutation because it entails limited communication between the nodes.
      This confines the effects of a mutation to few residues instead of propagating
      them to many residues via hubs. We propose that intermolecular beta-strand
      interfaces are organized in networks that tolerate amino acid mutation to avoid
      chain dissociation, the first step towards fiber formation. This is tested by
      looking at the intermolecular beta-strand network of the p53 tetramer. 

PMID- 24733381
TI  - Establishment and maintenance of B cell identity.
AB  - B lymphocyte differentiation is dependent on an intricate interplay of
      transcription factors and signaling pathways to establish a lineage-specific
      program of gene expression. Functional perturbations of several transcription
      factors by gain- or loss-of-function experiments indicated that E2A, EBF1, and
      FoxO1 are required for the specification of the B cell lineage, whereas Pax5
      antagonizes alternative cell fates by repressing genes that allow for
      responsiveness to T lymphoid- and myeloid-promoting signals. However, genome-wide
      analysis of EBF1-binding sites and their functional interrogation indicated that
      EBF1 is involved in both activation of the B cell program and repression of
      alternative cell fates. Recent studies indicate that EBF1 function is required
      throughout the B cell lineage until the onset of plasma cell differentiation and
      includes a role in the maintenance of B cell identity. Thus, early B cell
      differentiation requires intertwined networks of transcription factors in which
      EBF1 collaborates with E2A and FoxO1 to activate the B lineage program and acts
      together with Pax5 to antagonize alternative cell fates. 

PMID- 24733383
TI  - The relationship between physical activity and aging symptoms among community
      dwelling men aged 40-70 years in Shanghai, China.
AB  - BACKGROUND: Research on the relationship between physical activity and aging
      symptoms among men is limited in China. METHODS: Eight hundred nineteen
      participants aged 40 to 70 (mean age = 58.25) were administered the International
      Physical Activity Questionnaire and Aging Males' Symptoms scale (AMS) in face-to
      face interviews between 2009 and 2010. Ordinal logistic regression and
      generalized linear models were used to examine severity of aging symptoms. AMS
      total score and subscale scores (psychological, somatic, and sexual health) were
      examined according to physical activity level. RESULTS: Participants who reported
      higher levels of physical activity were significantly less likely to develop
      aging symptoms compared with those who reported lower levels of physical
      activity, both with (odds ratio [OR] = 0.78, 95% confidence interval [CI]: 0.64
      to 0.95) and without (OR = 0.70, 95% CI: 0.56 to 0.87) adjustment for age, body
      mass index (BMI), smoking, alcohol consumption, and chronic disease. In addition,
      physical activity was negatively correlated with AMS total score (P < .01) and
      scores for somatic (P < .01) and sexual (P = .04) health. After covariate
      adjustment, the negative correlation between physical activity and all AMS scores
      remained significant (P < .01). CONCLUSION: Physical activity is negatively
      correlated with aging symptoms among middle-aged men in Shanghai.

PMID- 24733382
TI  - MxA mRNA quantification and disability progression in interferon beta-treated
      multiple sclerosis patients.
AB  - Even though anti-interferon beta (IFNbeta) antibodies are the main determinants
      of IFNbeta bioactivity loss and Myxovirus-resistance protein A (MxA) is the most
      established marker of IFNbeta biological activity in IFNbeta-treated multiple
      sclerosis patients, their usefulness in the routine clinical practice is still
      debated. Therefore, 118 multiple sclerosis patients naive for treatment were
      enrolled for a 3-year longitudinal observational study mimicking the conditions
      of a real-world setting. In order to evaluate the kinetics of bioactivity loss in
      blood samples obtained every 6 months after therapy initiation, MxA and
      interferon receptor isoform/subunit mRNA were quantified by real-time PCR, anti
      IFNbeta binding antibodies were detected by radioimmunoprecipitation, and
      neutralizing antibodies by cytopathic effect inhibition assay. Clinical measures
      of disease activity and disability progression were also obtained at all time
      points. We found that, at the individual-patient level, the response to IFNbeta
      therapy was extremely heterogeneous, including patients with stable or
      transitory, early or late loss of IFNbeta bioactivity, and patients with samples
      lacking MxA mRNA induction in spite of absence of antibodies. No interferon
      receptor isoform alterations that could explain these findings were found. At the
      group level, none of these biological features correlated with the measures of
      clinical disease activity or progression. However, when MxA mRNA was evaluated
      not at the single time point as a dichotomic marker (induced vs. non-induced),
      but as the mean of its values measured over the 6-to-24 month period, the
      increasing average MxA predicted a decreasing risk of short-term disability
      progression, independently from the presence of relapses. Therefore, a more
      bioactive treatment, even if unable to suppress relapses, reduces their severity
      by an amount that is proportional to MxA levels. Together with its feasibility in
      the routine laboratory setting, these data warrant the quantification of MxA mRNA
      as a primary tool for a routine monitoring of IFNbeta therapy. 

PMID- 24733384
TI  - Incidentaloma fatigue.

PMID- 24733380
TI  - The "histone mimicry" by pathogens.
AB  - One of the defining characteristics of human and animal viruses is their ability
      to suppress host antiviral responses. Viruses express proteins that impair the
      detection of viral nucleic acids by host pattern-recognition receptors, block
      signaling pathways that lead to the synthesis of type I interferons and other
      cytokines, or prevent the activation of virus-induced genes. We have identified a
      novel mechanism of virus-mediated suppression of antiviral gene expression that
      relies on the presence of histone-like sequences (histone mimics) in viral
      proteins. We describe how viral histone mimics can interfere with key regulators
      of gene expression and contribute to the suppression of antiviral responses. We
      also describe how viral histone mimics can facilitate the identification of novel
      mechanisms of antiviral gene regulation and lead to the development of drugs that
      use histone mimicry for interference with gene expression during diseases. 

PMID- 24733387
TI  - Glycerol monomycolate is a novel ligand for the human, but not mouse macrophage
      inducible C-type lectin, Mincle.
AB  - An array of lipidic compounds that constitute the cell wall of mycobacteria is
      recognized by host receptors. Examples include trehalose dimycolate (TDM), which
      is a major surface-exposed glycolipid of mycobacteria, that interacts with the
      macrophage inducible C-type lectin, Mincle, and exerts its highly potent adjuvant
      functions. Recent evidence has suggested that glycerol monomycolate (GroMM),
      another mycolate-containing lipid species produced by mycobacteria, can stimulate
      innate immune cells; however, its specific host receptors have yet to be
      identified. We here demonstrated that cell transfectants expressing human Mincle
      (hMincle) reacted to both TDM and GroMM, while those expressing mouse Mincle
      (mMincle) only reacted to TDM and failed to recognize GroMM. Studies using domain
      swap chimeras confirmed that the ectodomain of hMincle, but not that of mMincle,
      interacted with GroMM, and site-directed mutagenesis analyses revealed that short
      stretches of amino acid residues at positions 174-176 and 195-196 were involved
      in GroMM recognition. To further substantiate the differential recognition of
      GroMM by hMincle and mMincle, hMincle transgenic/mMincle knock-out mice (i.e.
      hMincle(+) mice) were established and compared with non-transgenic mice (i.e.
      mMincle(+) mice). We showed that macrophages derived from hMincle(+) mice were
      activated by GroMM and produced inflammatory cytokines, whereas those derived
      from mMincle(+) mice did not exhibit any reactivity to GroMM. Furthermore, local
      inflammatory responses were elicited in the GroMM-injected skin of hMincle(+),
      but not mMincle(+) mice. These results demonstrated that GroMM is a unique ligand
      for hMincle that is not recognized by mMincle. 

PMID- 24733388
TI  - Generating symmetry in the asymmetric ATP-binding cassette (ABC) transporter Pdr5
      from Saccharomyces cerevisiae.
AB  - Pdr5 is a plasma membrane-bound ABC transporter from Saccharomyces cerevisiae and
      is involved in the phenomenon of resistance against xenobiotics, which are
      clinically relevant in bacteria, fungi, and humans. Many fungal ABC transporters
      such as Pdr5 display an inherent asymmetry in their nucleotide-binding sites
      (NBS) unlike most of their human counterparts. This degeneracy of the NBSs is
      very intriguing and needs explanation in terms of structural and functional
      relevance. In this study, we mutated nonconsensus amino acid residues in the NBSs
      to its consensus counterpart and studied its effect on the function of the
      protein and effect on yeast cells. The completely "regenerated" Pdr5 protein was
      severely impaired in its function of ATP hydrolysis and of rhodamine 6G
      transport. Moreover, we observe alternative compensatory mechanisms to counteract
      drug toxicity in some of the mutants. In essence, we describe here the first
      attempts to restore complete symmetry in an asymmetric ABC transporter and to
      study its effects, which might be relevant to the entire class of asymmetric ABC
      transporters. 

PMID- 24733389
TI  - Atypical OmpR/PhoB subfamily response regulator GlnR of actinomycetes functions
      as a homodimer, stabilized by the unphosphorylated conserved Asp-focused charge
      interactions.
AB  - The OmpR/PhoB subfamily protein GlnR of actinomycetes is an orphan response
      regulator that globally coordinates the expression of genes related to nitrogen
      metabolism. Biochemical and genetic analyses reveal that the functional GlnR from
      Amycolatopsis mediterranei is unphosphorylated at the potential phosphorylation
      Asp(50) residue in the N-terminal receiver domain. The crystal structure of this
      receiver domain demonstrates that it forms a homodimer through the alpha4-beta5
      alpha5 dimer interface highly similar to the phosphorylated typical response
      regulator, whereas the so-called "phosphorylation pocket" is not conserved, with
      its space being occupied by an Arg(52) from the beta3-alpha3 loop. Both in vitro
      and in vivo experiments confirm that GlnR forms a functional homodimer via its
      receiver domain and suggest that the charge interactions of Asp(50) with the
      highly conserved Arg(52) and Thr(9) in the receiver domain may be crucial in
      maintaining the proper conformation for homodimerization, as also supported by
      molecular dynamics simulations of the wild type GlnR versus the deficient mutant
      GlnR(D50A). This model is backed by the distinct phenotypes of the total
      deficient GlnR(R52A/T9A) double mutant versus the single mutants of GlnR (i.e.
      D50N, D50E, R52A and T9A), which have only minor effects upon both dimerization
      and physiological function of GlnR in vivo, albeit their DNA binding ability is
      weakened compared with that of the wild type. By integrating the supportive data
      of GlnRs from the model Streptomyces coelicolor and the pathogenic Mycobacterium
      tuberculosis, we conclude that the actinomycete GlnR is atypical with respect to
      its unphosphorylated conserved Asp residue being involved in the critical
      Arg/Asp/Thr charge interactions, which is essential for maintaining the
      biologically active homodimer conformation. 

PMID- 24733390
TI  - Golgi phosphoprotein 3 mediates the Golgi localization and function of protein O
      linked mannose beta-1,2-N-acetlyglucosaminyltransferase 1.
AB  - GOLPH3 is a highly conserved protein found across the eukaryotic lineage. The
      yeast homolog, Vps74p, interacts with and maintains the Golgi localization of
      several mannosyltransferases, which is subsequently critical for N- and O
      glycosylation in yeast. Through the use of a T7 phage display, we discovered a
      novel interaction between GOLPH3 and a mammalian glycosyltransferase, POMGnT1,
      which is involved in the O-mannosylation of alpha-dystroglycan. The cytoplasmic
      tail of POMGnT1 was found to be critical for mediating its interaction with
      GOLPH3. Loss of this interaction resulted in the inability of POMGnT1 to localize
      to the Golgi and reduced the functional glycosylation of alpha-dystroglycan. In
      addition, we showed that three clinically relevant mutations present in the stem
      domain of POMGnT1 mislocalized to the endoplasmic reticulum, highlighting the
      importance of identifying the molecular mechanisms responsible for Golgi
      localization of glycosyltransferases. Our findings reveal a novel role for GOLPH3
      in mediating the Golgi localization of POMGnT1. 

PMID- 24733391
TI  - Two residues predominantly dictate functional difference in motility between
      Shewanella oneidensis flagellins FlaA and FlaB.
AB  - Nearly half of flagellated microorganisms possess a multiple-flagellin system.
      Although a functional filament can be formed from one of multiple flagellins
      alone in many bacteria, it is more common that one flagellin is the major
      constituent and others contribute. Underlying mechanisms proposed for such
      scenarios cover flagellin regulation of various levels, including transcription,
      translation, post-translational modification, secretion, and filament assembly.
      In Shewanella oneidensis, the flagellar filament is composed of FlaA and FlaB
      flagellins; the latter is the major one in terms of motility. In this study, we
      showed that regulation of all levels except for filament assembly is
      indistinguishable between these two flagellins. Further analyses revealed that
      two amino acid residues predominantly dictated functional difference with respect
      to motility. Given that Shewanella prefer a solid surface-associated life style,
      of which filaments consisting of either FlaA or FlaB are equally supportive, we
      envision that roles of flagella in surface adhesion and formation of bacterial
      communities are particularly important for their survival and proliferation in
      these specific niches. 

PMID- 24733392
TI  - Telomerase reverse transcriptase has an extratelomeric function in somatic cell
      reprogramming.
AB  - Reactivation of the endogenous telomerase reverse transcriptase (TERT) catalytic
      subunit and telomere elongation occur during the reprogramming of somatic cells
      to induced pluripotent stem (iPS) cells. However, the role of TERT in the
      reprogramming process is unclear. To clarify its function, the reprogramming
      process was examined in TERT-KO somatic cells. To exclude the effect of telomere
      elongation, tail-tip fibroblasts (TTFs) from first generation TERT-KO mice were
      used. Although iPS cells were successfully generated from TERT-KO TTFs, the
      efficiency of reprogramming these cells was markedly lower than that of WT TTFs.
      The gene expression profiles of iPS cells induced from TERT-KO TTFs were similar
      to those of WT iPS cells and ES cells, and TERT-KO iPS cells formed teratomas
      that differentiated into all three germ layers. These data indicate that TERT
      plays an extratelomeric role in the reprogramming process, but its function is
      dispensable. However, TERT-KO iPS cells showed transient defects in growth and
      teratoma formation during continuous growth. In addition, TERT-KO iPS cells
      developed chromosome fusions that accumulated with increasing passage numbers,
      consistent with the fact that TERT is essential for the maintenance of genome
      structure and stability in iPS cells. In a rescue experiment, an enzymatically
      inactive mutant of TERT (D702A) had a positive effect on somatic cell
      reprogramming of TERT-KO TTFs, which confirmed the extratelomeric role of TERT in
      this process. 

PMID- 24733393
TI  - The tetraspanin CD81 protein increases melanoma cell motility by up-regulating
      metalloproteinase MT1-MMP expression through the pro-oncogenic Akt-dependent Sp1
      activation signaling pathways.
AB  - Despite the importance of multiple tetraspanin proteins in cancer invasion and
      metastasis, little is known about the role and significance of tetraspanin CD81
      in these processes. In the present study, we examined CD81 effects on melanoma
      cell invasiveness and metastasis. Transfection of CD81 into melanoma cells
      lacking endogenous CD81 expression significantly enhanced the migrating,
      invasive, and metastatic abilities of melanoma cells. Interestingly, membrane
      type 1 matrix metalloproteinase (MT1-MMP) expression was found in CD81-expressing
      melanoma cells but not in CD81-deficient cells. siRNA knockdown of CD81 in
      melanoma cells with endogenous CD81 demonstrated decreased MT1-MMP levels and
      cell motility. Notably, CD81-induced cell migration was abrogated by antibody
      blocking and siRNA knockdown of MT1-MMP, indicating that MT1-MMP is responsible
      for CD81-stimulated melanoma cell migration. Promoter analysis revealed an
      essential role of the Sp1 transcription factor in CD81-induced MT1-MMP
      transcription. We also demonstrate that the Sp1-activating Akt pathway is
      involved in adhesion-dependent CD81 signaling to induce MT1-MMP expression and
      cell motility. Importantly, human skin cancer tissue specimens displayed a
      positive correlation of CD81 with MT1-MMP expression levels and a close
      association of CD81 with malignant melanomas. Taken together, these results
      strongly suggest that CD81 stimulates melanoma cell motility by inducing MT1-MMP
      expression through the Akt-dependent Sp1 activation signaling pathway, leading to
      increased melanoma invasion and metastasis. 

PMID- 24733394
TI  - Mitochondrial MTHFD2L is a dual redox cofactor-specific methylenetetrahydrofolate
      dehydrogenase/methenyltetrahydrofolate cyclohydrolase expressed in both adult and
      embryonic tissues.
AB  - Mammalian mitochondria are able to produce formate from one-carbon donors such as
      serine, glycine, and sarcosine. This pathway relies on the mitochondrial pool of
      tetrahydrofolate (THF) and several folate-interconverting enzymes in the
      mitochondrial matrix. We recently identified MTHFD2L as the enzyme that catalyzes
      the oxidation of 5,10-methylenetetrahydrofolate (CH2-THF) in adult mammalian
      mitochondria. We show here that the MTHFD2L enzyme is bifunctional, possessing
      both CH2-THF dehydrogenase and 5,10-methenyl-THF cyclohydrolase activities. The
      dehydrogenase activity can use either NAD(+) or NADP(+) but requires both
      phosphate and Mg(2+) when using NAD(+). The NADP(+)-dependent dehydrogenase
      activity is inhibited by inorganic phosphate. MTHFD2L uses the mono- and
      polyglutamylated forms of CH2-THF with similar catalytic efficiencies. Expression
      of the MTHFD2L transcript is low in early mouse embryos but begins to increase at
      embryonic day 10.5 and remains elevated through birth. In adults, MTHFD2L is
      expressed in all tissues examined, with the highest levels observed in brain and
      lung. 

PMID- 24733395
TI  - Nitric oxide and heat shock protein 90 activate soluble guanylate cyclase by
      driving rapid change in its subunit interactions and heme content.
AB  - The chaperone heat shock protein 90 (hsp90) associates with signaling proteins in
      cells including soluble guanylate cyclase (sGC). hsp90 associates with the heme
      free (apo) sGC-beta1 subunit and helps to drive heme insertion during maturation
      of sGC to its NO-responsive active form. Here, we found that NO caused apo-sGC
      beta1 to rapidly and transiently dissociate from hsp90 and associate with sGC
      alpha1 in cells. This NO response (i) required that hsp90 be active and that
      cellular heme be available and be capable of inserting into apo-sGC-beta1; (ii)
      was associated with an increase in sGC-beta1 heme content; (iii) could be
      mimicked by the heme-independent sGC activator BAY 60-2770; and (iv) was followed
      by desensitization of sGC toward NO, sGC-alpha1 disassociation, and reassociation
      with hsp90. Thus, NO promoted a rapid, transient, and hsp90-dependent heme
      insertion into the apo-sGC-beta1 subpopulation in cells, which enabled it to
      combine with the sGC-alpha1 subunit to form the mature enzyme. The driving
      mechanism likely involves conformational changes near the heme site in sGC-beta1
      that can be mimicked by the pharmacologic sGC activator. Such dynamic interplay
      between hsp90, apo-sGC-beta1, and sGC-alpha1 in response to NO is unprecedented
      and represent new steps by which cells can modulate the heme content and activity
      of sGC for signaling cascades. 

PMID- 24733396
TI  - Point mutations in dimerization motifs of the transmembrane domain stabilize
      active or inactive state of the EphA2 receptor tyrosine kinase.
AB  - The EphA2 receptor tyrosine kinase plays a central role in the regulation of cell
      adhesion and guidance in many human tissues. The activation of EphA2 occurs after
      proper dimerization/oligomerization in the plasma membrane, which occurs with the
      participation of extracellular and cytoplasmic domains. Our study revealed that
      the isolated transmembrane domain (TMD) of EphA2 embedded into the lipid bicelle
      dimerized via the heptad repeat motif L(535)X3G(539)X2A(542)X3V(546)X2L(549)
      rather than through the alternative glycine zipper motif A(536)X3G(540)X3G(544)
      (typical for TMD dimerization in many proteins). To evaluate the significance of
      TMD interactions for full-length EphA2, we substituted key residues in the heptad
      repeat motif (HR variant: G539I, A542I, G553I) or in the glycine zipper motif (GZ
      variant: G540I, G544I) and expressed YFP-tagged EphA2 (WT, HR, and GZ variants)
      in HEK293T cells. Confocal microscopy revealed a similar distribution of all
      EphA2-YFP variants in cells. The expression of EphA2-YFP variants and their
      kinase activity (phosphorylation of Tyr(588) and/or Tyr(594)) and ephrin-A3
      binding were analyzed with flow cytometry on a single cell basis. Activation of
      any EphA2 variant is found to occur even without ephrin stimulation when the
      EphA2 content in cells is sufficiently high. Ephrin-A3 binding is not affected in
      mutant variants. Mutations in the TMD have a significant effect on EphA2
      activity. Both ligand-dependent and ligand-independent activities are enhanced
      for the HR variant and reduced for the GZ variant compared with the WT. These
      findings allow us to suggest TMD dimerization switching between the heptad repeat
      and glycine zipper motifs, corresponding to inactive and active receptor states,
      respectively, as a mechanism underlying EphA2 signal transduction. 

PMID- 24733398
TI  - The politics of color: preferences for Republican red versus Democratic blue.
AB  - The present study reveals that Election Day differentially affects the color
      preferences of US Republicans and Democrats. Voters' preferences for Republican
      red and Democratic blue were assessed, along with several distractor colors, on
      and around the 2010 interim and 2012 presidential elections. On non-Election
      Days, Republicans and Democrats preferred Republican red equally, and Republicans
      actually preferred Democratic blue more than Democrats did. On Election Day,
      however, Republicans' and Democrats' color preferences changed to become more
      closely aligned with their own party's colors. Republicans liked Republican red
      more than Democrats did, and no longer preferred Democratic blue more than
      Democrats did. These results are consistent with the hypothesis that color
      preferences are determined by people's preferences for correspondingly colored
      objects/entities (Palmer & Schloss in Proceedings of the National Academy of
      Sciences 107:8877-8882, 2010). They further suggest that color preferences are
      calculated at a given moment, depending on which color-object associations are
      currently most activated or salient. Color preferences are thus far more dynamic
      and context-dependent than has previously been believed. 

PMID- 24733397
TI  - The retinaldehyde reductase activity of DHRS3 is reciprocally activated by
      retinol dehydrogenase 10 to control retinoid homeostasis.
AB  - The retinoic acid-inducible dehydrogenase reductase 3 (DHRS3) is thought to
      function as a retinaldehyde reductase that controls the levels of all-trans
      retinaldehyde, the immediate precursor for bioactive all-trans-retinoic acid.
      However, the weak catalytic activity of DHRS3 and the lack of changes in
      retinaldehyde conversion to retinol and retinoic acid in the cells overexpressing
      DHRS3 undermine its role as a physiologically important all-trans-retinaldehyde
      reductase. This study demonstrates that DHRS3 requires the presence of retinol
      dehydrogenase 10 (RDH10) to display its full catalytic activity. The RDH10
      activated DHRS3 acts as a robust high affinity all-trans-retinaldehyde-specific
      reductase that effectively converts retinaldehyde back to retinol, decreasing the
      rate of retinoic acid biosynthesis. In turn, the retinol dehydrogenase activity
      of RDH10 is reciprocally activated by DHRS3. At E13.5, DHRS3-null embryos have ~4
      fold lower levels of retinol and retinyl esters, but only slightly elevated
      levels of retinoic acid. The membrane-associated retinaldehyde reductase and
      retinol dehydrogenase activities are decreased by ~4- and ~2-fold, respectively,
      in Dhrs3(-/-) embryos, and Dhrs3(-/-) mouse embryonic fibroblasts exhibit reduced
      metabolism of both retinaldehyde and retinol. Neither RDH10 nor DHRS3 has to be
      itself catalytically active to activate each other. The transcripts encoding
      DHRS3 and RDH10 are co-localized at least in some tissues during development. The
      mutually activating interaction between the two related proteins may represent a
      highly sensitive and conserved mechanism for precise control over the rate of
      retinoic acid biosynthesis. 

PMID- 24733401
TI  - Comparison of cardiac troponin T and N-terminal pro-B-type natriuretic peptide
      between fetuses with hemoglobin Bart's disease and nonanemic fetuses.
AB  - OBJECTIVE: The objective of this study was to compare the levels of fetal serum
      cardiac troponin T (cTnT), representing cardiac injury, and N-terminal pro-B-type
      natriuretic peptide (nt-proBNP), representing cardiac volume overload, between
      fetuses affected and not affected by hemoglobin (Hb) Bart's disease, as well as
      between anemic and nonanemic fetuses. METHODS: One hundred fourteen pregnancies
      at risk for fetal Hb Bart's disease scheduled for cordocentesis at 18 to 22 weeks
      were recruited into the study. Fetal blood was collected to test for cTnT, nt
      proBNP and Hb levels as well as Hb typing. RESULTS: Serum nt-proBNP was
      significantly higher in Hb Bart's fetuses (24 cases) than in unaffected fetuses
      (63 cases), whereas cTnT was significantly lower in the affected group than in
      the unaffected group. The serum nt-proBNP levels significantly increased with the
      degree of fetal anemia; cTnT levels decreased in fetuses with high degree of
      anemia. CONCLUSIONS: At mid-pregnancy, nt-proBNP was significantly higher in
      fetuses with Hb Bart's disease than in nonanemic fetuses; cTnT was significantly
      lower in anemic than in normal fetuses. This study suggests that cardiomegaly
      from fetal anemia in early gestation is not associated with fetal cardiac injury
      or myocardial dysfunction but presents as cardiac volume overload from a
      compensatory process to maintain adequate tissue oxygenation.

PMID- 24733402
TI  - Ethnography in community psychology: promises and tensions.
AB  - Community psychology recognizes the need for research methods that illuminate
      context, culture, diversity, and process. One such method, ethnography, has
      crossed into multiple disciplines from anthropology, and indeed, community
      psychologists are becoming community ethnographers. Ethnographic work stands at
      the intersection of bridging universal questions with the particularities of
      people and groups bounded in time, geographic location, and social location.
      Ethnography is thus historical and deeply contextual, enabling a rich, in-depth
      understanding of communities that is aligned with the values and goals of
      community psychology. The purpose of this paper is to elucidate the potential of
      ethnography for community psychology and to encourage its use within the field as
      a method to capture culture and context, to document process, and to reveal how
      social change and action occur within and through communities. We discuss the
      method of ethnography, draw connections to community psychology values and goals,
      and identify tensions from our experiences doing ethnography. Overall, we assert
      that ethnography is a method that resonates with community psychology and present
      this paper as a resource for those interested in using this method in their
      research or community activism. 

PMID- 24733404
TI  - Symmetry-breaking magnetic fields create a vortex fluid that exhibits a negative
      viscosity, active wetting, and strong mixing.
AB  - There are many areas of science and technology where being able to generate
      vigorous, noncontact flow would be desirable. We have discovered that three
      dimensional, time-dependent electric or magnetic fields having key symmetries can
      be used to generate controlled fluid motion by the continuous injection of
      energy. Unlike natural convection, this approach does not require a thermal
      gradient as an energy source, nor does it require gravity, so space applications
      are feasible. The result is a highly active material we call a vortex fluid. The
      homogeneous torque density of this fluid enables it to climb walls, induce
      ballistic droplet motion, and mix vigorously, even in such complex geometries as
      porous media. This vortex fluid can also exhibit a negative viscosity, which can
      immeasurably extend the control range of the "smart fluids" used in electro- and
      magnetorheological devices and can thus significantly increase their performance.
      Because the applied fields are uniform and modest in strength, vortex fluids of
      any scale can be created, making applications of any size, from directing
      microdroplet motion to controlling damping in magnetorheological dampers that
      protect bridges and buildings from earthquakes, feasible. 

PMID- 24733403
TI  - The gut microbial community of Midas cichlid fish in repeatedly evolved limnetic
      benthic species pairs.
AB  - Gut bacterial communities are now known to influence a range of fitness related
      aspects of organisms. But how different the microbial community is in closely
      related species, and if these differences can be interpreted as adaptive is still
      unclear. In this study we compared microbial communities in two sets of closely
      related sympatric crater lake cichlid fish species pairs that show similar
      adaptations along the limnetic-benthic axis. The gut microbial community
      composition differs in the species pair inhabiting the older of two crater lakes.
      One major difference, relative to other fish, is that in these cichlids that live
      in hypersaline crater lakes, the microbial community is largely made up of
      Oceanospirillales (52.28%) which are halotolerant or halophilic bacteria. This
      analysis opens up further avenues to identify candidate symbiotic or co-evolved
      bacteria playing a role in adaptation to similar diets and life-styles or even
      have a role in speciation. Future functional and phylosymbiotic analyses might
      help to address these issues. 

PMID- 24733405
TI  - Lymphomatoid plaquosis - a CD30+ lymphoproliferative rash exhibiting a
      predilection for recurrence on the same skin sites.

PMID- 24733406
TI  - Detection of transgene expression using hyperpolarized 13C urea and diffusion
      weighted magnetic resonance spectroscopy.
AB  - PURPOSE: To assess the potential of a gene reporter system, based on a urea
      transporter (UTB) and hyperpolarized [(13) C]urea. METHODS: Mice were implanted
      subcutaneously with either unmodified control cells or otherwise identical cells
      expressing UTB. After injection of hyperpolarized [(13) C]urea, a spin echo
      sequence was used to measure urea concentration, T1 , and diffusion in control
      and UTB-expressing tissue. RESULTS: The apparent diffusion coefficient of
      hyperpolarized urea was 21% lower in tissue expressing UTB, in comparison with
      control tissue (P < 0.05, 1-tailed t-test, n = 6 in each group). No difference in
      water apparent diffusion coefficient or cellularity between these tissues was
      found, indicating that they were otherwise similar in composition. CONCLUSION:
      Expression of UTB, by mediating cell uptake of urea, lowers the apparent
      diffusion coefficient of hyperpolarized (13) C urea in tissue and thus the
      transporter has the potential to be used as a magnetic resonance-based gene
      reporter in vivo. Magn Reson Med 73:1401-1406, 2015. (c) 2014 Wiley Periodicals,
      Inc.

PMID- 24733407
TI  - Frailty in heart failure.
AB  - Considering the increasing age of individuals affected with heart failure (HF), a
      specific approach to their treatment is required, with more attention paid to
      geriatric conditions such as poor mobility, multiple disabilities, and cognitive
      impairment. Frailty is a distinct biological syndrome reflecting decreased
      physiologic reserve and resistance to stressors. It was shown to occur frequently
      in patients with heart failure, with the prevalence ranging from 15 to 74 %,
      depending on the studied population and the method of assessment. We reviewed
      literature data on the influence of frailty, skeletal abnormalities,
      comorbidities and geriatric condition on diagnosis, treatment, and outcomes in
      elderly patients with HF. Identification of frailty in patients with HF is
      important from the clinical point of view, as this condition exerts unfavorable
      effects on the course of heart failure. Frailty contributes to a higher frequency
      of visits to emergency departments, hospitalizations, and mortality in patients
      with HF. Exercise may improve mobility, and nursing support can be implemented to
      help the patients adhere to medications. Therefore, frail patients should be
      diagnosed and treated according to available guidelines, and successfully
      educated about their condition. 

PMID- 24733408
TI  - Results of a multicenter, double-blind, randomized, parallel-group, placebo
      controlled, single-dose study comparing the fixed combination of acetaminophen,
      acetylsalicylic acid, and caffeine with ibuprofen for acute treatment of patients
      with severe migraine.
AB  - INTRODUCTION: In a multicenter, double-blind, randomized, parallel-group, placebo
      controlled, single-dose study (n = 1555), a fixed combination of acetaminophen
      500 mg, acetylsalicylic acid 500 mg, and caffeine 130 mg (AAC) was compared with
      ibuprofen 400 mg (IB) and placebo (PLA) for acute treatment of migraine. SUBJECTS
      AND METHODS: An exploratory post-hoc analysis compared AAC with IB and PLA in the
      subset of patients with severe pain at baseline (n = 660). RESULTS: At most time
      points, AAC and IB relieved the pain and associated symptoms of severe migraine
      significantly better than PLA (p <= 0.05). AAC was significantly superior to IB
      for pain relief at 45 minutes and at one, two, three, and four hours postdose (p
      < 0.04); pain intensity difference from one hour through three hours (p < 0.05);
      headache response at two hours (p = 0.04); functional disability reduced to
      little or none at three hours (p = 0.013); freedom from phonophobia at three
      hours (p = 0.04) and photophobia at 15 minutes postdose (p = 0.03); and use of
      rescue medication (p = 0.018). AAC patients also reported meaningful pain relief
      16 minutes faster than IB patients (132 minutes vs 148 minutes, p = 0.026).
      CONCLUSIONS: In patients with severe baseline migraine pain, AAC and IB are
      significantly more effective than PLA, and AAC provides significantly faster and
      more effective pain relief than IB.

PMID- 24733409
TI  - Accuracy of ultrasonography and magnetic resonance imaging in the diagnosis of
      placenta accreta.
AB  - PURPOSE: To evaluate the accuracy of ultrasonography and magnetic resonance
      imaging (MRI) in the diagnosis of placenta accreta and to define the most
      relevant specific ultrasound and MRI features that may predict placental
      invasion. MATERIAL AND METHODS: This study was approved by the institutional
      review board of the French College of Obstetricians and Gynecologists. We
      retrospectively reviewed the medical records of all patients referred for
      suspected placenta accreta to two university hospitals from 01/2001 to 05/2012.
      Our study population included 42 pregnant women who had been investigated by both
      ultrasonography and MRI. Ultrasound images and MRI were blindly reassessed for
      each case by 2 raters in order to score features that predict abnormal placental
      invasion. RESULTS: Sensitivity in the diagnosis of placenta accreta was 100% with
      ultrasound and 76.9% for MRI (P = 0.03). Specificity was 37.5% with
      ultrasonography and 50% for MRI (P = 0.6). The features of greatest sensitivity
      on ultrasonography were intraplacental lacunae and loss of the normal
      retroplacental clear space. Increased vascularization in the uterine serosa
      bladder wall interface and vascularization perpendicular to the uterine wall had
      the best positive predictive value (92%). At MRI, uterine bulging had the best
      positive predictive value (85%) and its combination with the presence of dark
      intraplacental bands on T2-weighted images improved the predictive value to 90%.
      CONCLUSION: Ultrasound imaging is the mainstay of screening for placenta accreta.
      MRI appears to be complementary to ultrasonography, especially when there are few
      ultrasound signs.

PMID- 24733411
TI  - Vedolizumab, a gut-specific monoclonal antibody, renews hope for an alternative
      to anti-TNF therapy in inflammatory bowel diseases.

PMID- 24733410
TI  - Mitochondrial morphological features are associated with fission and fusion
      events.
AB  - Mitochondria are dynamic organelles that undergo constant remodeling through the
      regulation of two opposing processes, mitochondrial fission and fusion. Although
      several key regulators and physiological stimuli have been identified to control
      mitochondrial fission and fusion, the role of mitochondrial morphology in the two
      processes remains to be determined. To address this knowledge gap, we
      investigated whether morphological features extracted from time-lapse live-cell
      images of mitochondria could be used to predict mitochondrial fate. That is, we
      asked if we could predict whether a mitochondrion is likely to participate in a
      fission or fusion event based on its current shape and local environment. Using
      live-cell microscopy, image analysis software, and supervised machine learning,
      we characterized mitochondrial dynamics with single-organelle resolution to
      identify features of mitochondria that are predictive of fission and fusion
      events. A random forest (RF) model was trained to correctly classify mitochondria
      poised for either fission or fusion based on a series of morphological and
      positional features for each organelle. Of the features we evaluated,
      mitochondrial perimeter positively correlated with mitochondria about to undergo
      a fission event. Similarly mitochondrial solidity (compact shape) positively
      correlated with mitochondria about to undergo a fusion event. Our results
      indicate that fission and fusion are positively correlated with mitochondrial
      morphological features; and therefore, mitochondrial fission and fusion may be
      influenced by the mechanical properties of mitochondrial membranes. 

PMID- 24733412
TI  - A rich fossil record yields calibrated phylogeny for Acanthaceae (Lamiales) and
      evidence for marked biases in timing and directionality of intercontinental
      disjunctions.
AB  - More than a decade of phylogenetic research has yielded a well-sampled, strongly
      supported hypothesis of relationships within the large ( > 4000 species) plant
      family Acanthaceae. This hypothesis points to intriguing biogeographic patterns
      and asymmetries in sister clade diversity but, absent a time-calibrated estimate
      for this evolutionary history, these patterns have remained unexplored. Here, we
      reconstruct divergence times within Acanthaceae using fossils as calibration
      points and experimenting with both fossil selection and effects of invoking a
      maximum age prior related to the origin of Eudicots. Contrary to earlier reports
      of a paucity of fossils of Lamiales (an order of ~ 23,000 species that includes
      Acanthaceae) and to the expectation that a largely herbaceous to soft-wooded and
      tropical lineage would have few fossils, we recovered 51 reports of fossil
      Acanthaceae. Rigorous evaluation of these for accurate identification, quality of
      age assessment and utility in dating yielded eight fossils judged to merit
      inclusion in analyses. With nearly 10 kb of DNA sequence data, we used two sets
      of fossils as constraints to reconstruct divergence times. We demonstrate
      differences in age estimates depending on fossil selection and that enforcement
      of maximum age priors substantially alters estimated clade ages, especially in
      analyses that utilize a smaller rather than larger set of fossils. Our results
      suggest that long-distance dispersal events explain present-day distributions
      better than do Gondwanan or northern land bridge hypotheses. This biogeographical
      conclusion is for the most part robust to alternative calibration schemes. Our
      data support a minimum of 13 Old World (OW) to New World (NW) dispersal events
      but, intriguingly, only one in the reverse direction. Eleven of these 13 were
      among Acanthaceae s.s., which comprises > 90% of species diversity in the family.
      Remarkably, if minimum age estimates approximate true history, these 11 events
      occurred within the last ~ 20 myr even though Acanthaceae s.s is over 3 times as
      old. A simulation study confirmed that these dispersal events were significantly
      skewed toward the present and not simply a chance occurrence. Finally, we review
      reports of fossils that have been assigned to Acanthaceae that are substantially
      older than the lower Cretaceous estimate for Angiosperms as a whole (i.e., the
      general consensus that has resulted from several recent dating and fossil-based
      studies in plants). This is the first study to reconstruct divergence times among
      clades of Acanthaceae and sets the stage for comparative evolutionary research in
      this and related families that have until now been thought to have extremely poor
      fossil resources.

PMID- 24733413
TI  - Targeted BRAF inhibition impacts survival in melanoma patients with high levels
      of Wnt/beta-catenin signaling.
AB  - Unprecedented clinical responses have been reported in advanced stage metastatic
      melanoma patients treated with targeted inhibitors of constitutively activated
      mutant BRAF, which is present in approximately half of all melanomas. We and
      others have previously observed an association of elevated nuclear beta-catenin
      with improved survival in molecularly-unselected melanoma patients. This study
      sought to determine whether levels of Wnt/beta-catenin signaling in melanoma
      tumors prior to treatment might predict patient responses to BRAF inhibitors
      (BRAFi). We performed automated quantification of beta-catenin
      immunohistochemical expression in pretreatment BRAF-mutant tumors from 32 BRAFi
      treated melanoma patients. Unexpectedly, patients with higher nuclear beta
      catenin in their tumors did not exhibit the survival advantage previously
      observed in molecularly-unselected melanoma patients who did not receive BRAFi.
      In cultured melanoma cells treated with long-term BRAFi, activation of Wnt/beta
      catenin signaling is markedly inhibited, coinciding with a loss of the
      enhancement of BRAFi-induced apoptosis by WNT3A observed in BRAFi-naive cells.
      Together, these observations suggest that long-term treatment with BRAFi can
      impact the interaction between BRAF/MAPK and Wnt/beta-catenin signaling to affect
      patient outcomes. Studies with larger patient cohorts are required to determine
      whether nuclear beta-catenin expression correlates with clinical responses to
      BRAFi and to specific mechanisms of acquired resistance to BRAFi. Understanding
      these pathway interactions will be necessary to facilitate efforts to
      individualize therapies for melanoma patients. 

PMID- 24733414
TI  - Fingerprint changes in CSF composition associated with different aetiologies in
      human neonatal hydrocephalus: inflammatory cytokines.
AB  - PURPOSE: Hydrocephalus (HC) has a multifactorial and complex picture of
      pathophysiology due to aetiology, age at and duration since onset. We have
      previously identified distinctions in markers of cell death associated with
      different aetiologies. Here, we examined cerebrospinal fluid (CSF) from human HC
      neonates for cytokines to identify further distinguishing features of different
      aetiologies. METHODS: CSF was collected during routine lumbar puncture or
      ventricular tap from neonates with hydrocephalus, or with no neurological
      condition (normal controls). Total protein, Fas receptor, Fas ligand, stem cell
      factor (SCF), hepatocyte growth factor (HGF), vascular endothelial growth factor
      (VEGF), insulin growth factor-1 (IGF-1), tumour necrosis factor alpha (TNF-alpha)
      and interleukin 6 (IL-6) were measured and compared between 8 unaffected and 28
      HC neonatal CSF samples. RESULTS: Total protein was significantly (P < 0.05)
      raised in late-onset hydrocephalus (LOH). Fas receptor was raised (P < 0.05) in
      post-haemorrhagic hydrocephalus (PHH) and spina bifida with hydrocephalus
      (SB/HC), but no difference in Fas ligand was found. SCF was raised (P < 0.05) in
      SB/HC. HGF was found in all HC and was increased (P < 0.01) in PHH. Increased
      VEGF was found in PHH (P < 0.01) and SB/HC (P < 0.05). Variable levels of IL-6,
      TNF-alpha and IGF-1 were found in all HC groups compared with none in normal.
      CONCLUSIONS: LOH was unusual with significantly raised total protein indicating
      an inflammatory state. Increased Fas receptor, VEGF, IGF-1 and HGF suggest anti
      apoptotic and repair mechanism activation. By contrast, elevated TNF-alpha and IL
      6 indicate inflammatory processes in these neonatal brains. Taken with our
      previous study, these data indicate that different pathophysiology, inflammation
      and repair are occurring in HC of different aetiologies and that additional
      treatment strategies may benefit these infants in addition to fluid diversion.

PMID- 24733415
TI  - Insights into the regulation of DMSP synthesis in the diatom Thalassiosira
      pseudonana through APR activity, proteomics and gene expression analyses on cells
      acclimating to changes in salinity, light and nitrogen.
AB  - Despite the importance of dimethylsulphoniopropionate (DMSP) in the global
      sulphur cycle and climate regulation, the biological pathways underpinning its
      synthesis in marine phytoplankton remain poorly understood. The intracellular
      concentration of DMSP increases with increased salinity, increased light
      intensity and nitrogen starvation in the diatom Thalassiosira pseudonana. We used
      these conditions to investigate DMSP synthesis at the cellular level via analysis
      of enzyme activity, gene expression and proteome comparison. The activity of the
      key sulphur assimilatory enzyme, adenosine 5'-phosphosulphate reductase was not
      coordinated with increasing intracellular DMSP concentration. Under all three
      treatments coordination in the expression of sulphur assimilation genes was
      limited to increases in sulphite reductase transcripts. Similarly, proteomic 2D
      gel analysis only revealed an increase in phosphoenolpyruvate carboxylase
      following increases in DMSP concentration. Our findings suggest that increased
      sulphur assimilation might not be required for increased DMSP synthesis, instead
      the availability of carbon and nitrogen substrates may be important in the
      regulation of this pathway. This contrasts with the regulation of sulphur
      metabolism in higher plants, which generally involves up-regulation of several
      sulphur assimilatory enzymes. In T. pseudonana changes relating to sulphur
      metabolism were specific to the individual treatments and, given that little
      coordination was seen in transcript and protein responses across the three growth
      conditions, different patterns of regulation might be responsible for the
      increase in DMSP concentration seen under each treatment. 

PMID- 24733416
TI  - Potential first trimester metabolomic biomarkers of abnormal birth weight in
      healthy pregnancies.
AB  - OBJECTIVE: Macrosomia and low birth weight (LBW) can be associated with pregnancy
      complications and may affect the long-term health of the child. The aim of this
      study was to evaluate the metabolomic serum profiles of healthy pregnant women to
      identify early biomarkers of macrosomia and LBW and to understand mechanisms
      leading to abnormal fetal growth not related to mother's body mass index or
      presence of gestational diabetes. METHOD: Serum samples from 770 women were
      collected between the 12th and 14th gestational week. Delivery samples were
      divided into three groups according to the infant birth weight as follows: low,
      <2500 g; normal, 2500-4000 g; and high >4000 g. Samples from women with any
      complications of pregnancy were excluded. Serum fingerprinting was performed by
      LC-QTOF-MS. RESULTS: Lower levels of phospholipids, lysophospholipids, and
      monoacylglycerols; low vitamin D3 metabolites; and increased bilirubin level were
      associated with macrosomia. Because most changes involved lipids, as a concept of
      validation, adipocyte fatty acid-binding protein (A-FABP) levels were measured
      and found correlated with the studied lipids and birth weight. CONCLUSION: Serum
      fingerprinting in early pregnancy can predict the risk of macrosomia. Serum
      levels of A-FABP and several lipids are promising prognostic markers for
      macrosomia in healthy pregnancies.

PMID- 24733417
TI  - Evaluation of the effect of polymeric microneedle arrays of varying geometries in
      combination with a high-velocity applicator on skin permeability and irritation.
AB  - Polymeric microneedles offer the advantages of being both mass-producible and
      inexpensive. However, their weakness lies in the fact that they are not adequate
      for sharp fabrication of a needle tip, which is an important factor for effective
      penetration. We hypothesized that effective penetration can be achieved using a
      high-velocity application system. Therefore, in the present study, we
      investigated the influence of various polymeric microneedle array geometries on
      skin permeability and irritation using such a system. Volar forearms of 16
      healthy volunteers were treated using the microneedle system with four different
      parameters: applicator velocity (4.3, 6, and 8.5 m/s), tip radius (10, 15, and 20
      MUm), length (100, 200, and 300 MUm), and number of needles (189 and 305 on a 50
      mm(2) area). A higher velocity of piercing clearly enhanced skin permeability and
      damage. A larger tip radius resulted in lower skin permeability and irritation at
      an applicator velocity of 4.3 m/s but did not have an effect at 6 m/s. Skin
      permeability was positively variable, ranging from 100 to 200 MUm of needle
      length, and needle number showed no influence in the range investigated. In
      conclusion, a faster application speed could significantly enhance skin
      permeability and damage and compensate for insufficient penetration of the larger
      tip radius and shorter needles, which are also important factors for effective
      insertion. 

PMID- 24733419
TI  - Synthesis of Au130(SR)50 and Au(130-x)Ag(x)(SR)50 nanomolecules through core size
      conversion of larger metal clusters.
AB  - Gold nanomolecules with a precise number of metal atoms and thiolate ligands are
      being used for catalysis, biosensing, drug delivery and as alternative energy
      sources. Highly monodisperse products, with reproducible synthesis and complete
      characterization, are essential for these purposes. Post synthetic etching is
      used to synthesize highly stable gold nanomolecules. We report a synthetic
      protocol for the scalable synthesis of Au130(SR)50 for the first time, by etching
      of larger clusters via a core conversion process. Au130(SR)50 is not present in
      the crude product, but, is exclusively formed by etching larger clusters (>40
      kDa). This is the first evidence that larger nanocluster cores convert to
      Au130(SR)50. The special stability of Au130(SR)50 is confirmed by the formation
      of Au130-x(metal)x(SR)50, where R = CH2CH2Ph, C6H13, C12H25 and metal = Ag, Pd.
      AuxAg130-x(SR)50 is isolated and characterized with two different Au : Ag
      precursor ratios. Upon alloying there is a change in the optical features of this
      130-metal atom nanomolecule. To understand the process of etching and core
      conversion, a possible mechanism is being proposed. Highly stable nanomolecules
      like this can find potential applications in high temperature catalysis and
      sensing. 

PMID- 24733421
TI  - The neglect of nutrition in medical education: a firsthand look.

PMID- 24733422
TI  - Complete remission of refractory, ulcerated, primary cutaneous CD30+ anaplastic
      large cell lymphoma following brentuximab vedotin therapy.

PMID- 24733423
TI  - Chemotherapy and QT Prolongation: Overview With Clinical Perspective.
AB  - OPINION STATEMENT: Cardiotoxic adverse events are of concern to physicians
      treating cancer patients; they are encountered with a variety of agents. Cardiac
      events may delay the approval of new drugs or impose burdensome monitoring
      requirements as either part of the pre-approval process or in the daily use of
      these agents. Among the cardiac issues are the development of QT prolongation and
      the fear of torsades de pointes (TdP), an unusual yet potentially fatal form of
      ventricular tachycardia associated with QT prolongation. Several risk factors,
      including electrolyte imbalance and polypharmacy with concomitant QT prolonging
      agents use can increase the risk of TdP in cancer patients; separating the
      individual contributions of the various triggers for TdP remains problematic.
      Understanding the individual risk of QT prolongation associated with particular
      chemotherapies can better differentiate between those shown to have higher risk
      vs. those with lower risk potential. Cardiac monitoring and electrocardiogram
      analysis require recognition of the common challenges with regard to the precise
      measurement of the QT interval such as the presence of U waves, intraventricular
      conduction delays, and heart rate correction. Rapid identification and treatment
      of QT prolongation and TdP is critical in mitigating the risk of sudden cardiac
      death in cancer patients. A multidisciplinary treatment approach among
      cardiologists and oncologists should be employed to help facilitate an
      appropriate balance between oncologic efficacy and adverse cardiac events.

PMID- 24733424
TI  - Common metal of copper(0) as an efficient catalyst for preparation of nitriles
      and imines by controlling additives.
AB  - A novel, efficient, convenient and environmentally friendly approach for the
      synthesis of nitriles and imines from primary amines has been developed. Using
      commercially available red copper as the catalyst, ammonium bromide as the co
      catalyst and molecular oxygen as the sole oxidant, nitriles and imines can be
      afforded in high yields through benzylic oxidation. 

PMID- 24733425
TI  - Signal-transducing adaptor protein-2 regulates macrophage migration into
      inflammatory sites during dextran sodium sulfate induced colitis.
AB  - Signal-transducing adaptor protein-2 (STAP-2) was cloned as a c-fms/M-CSF
      receptor interacting protein. STAP-2 is an adaptor protein carrying pleckstrin
      homology and Src homology 2 like domains, as well as a YXXQ motif. STAP-2 has
      been indicated to have an ability to bind and modulate a variety of signaling and
      transcriptional molecules. Especially, our previous in vitro studies showed that
      STAP-2 is crucial for immune and/or inflammatory responses. Here, we have
      investigated the role of STAP-2 in intestinal inflammation in vivo. The
      disruption of STAP-2 attenuates dextran sodium sulfate induced colitis via
      inhibition of macrophage recruitment. To study whether hematopoietic or
      epithelial cell derived STAP-2 is required for this phenomenon, we generated BM
      chimeric mice. STAP-2-deficient macrophages impair the ability of CXCL12-induced
      migration. Intriguingly, STAP-2 also regulates production of proinflammatory
      chemokines and cytokines such as CXCL1 and TNF-alpha from intestinal epithelial
      cells. Therefore, STAP-2 has a potential to regulate plural molecular events
      during pathological inflammatory responses. Furthermore, our findings not only
      indicate that STAP-2 is important in regulating intestinal inflammation, but also
      provide new insights toward the development of novel therapeutic approaches. 

PMID- 24733426
TI  - The microbiome in non-alcoholic fatty liver disease: associations and
      implications.

PMID- 24733427
TI  - Expression analysis of heat shock protein 90 (HSP90) and Her2 in colon carcinoma.
AB  - PURPOSE: The molecular chaperone heat shock protein 90 (HSP90) plays an important
      role in several types of tumors also participating in the modulation of the
      activity of receptor tyrosine kinases activity such as members of the Her family.
      We evaluated the significance of HSP90 and Her2 expression in colon cancer.
      METHODS: HSP90 and Her2 expression was determined by immunohistochemistry and by
      fluorescence in situ hybridization (FISH) on 355 primary resected colon
      carcinomas. Results were correlated with pathologic features (Union for
      International Cancer Control (UICC) pTNM category, tumor localisation, tumor
      differentiation), additional molecular genetic characteristics (BRAF, KRAS
      mutational status, mismatch repair genes (MMR)), and survival. RESULTS: HSP90
      immunoreactivity was observed in various degrees. Fifty-one cases (14 %) were
      positive for Her2 (score 2+ and 3+) with 16/43 cases with Her2 2+ staining
      pattern showing amplification of Her2 determined by FISH. There was a significant
      correlation between high HSP90 expression and Her2 overexpression (p = 0.011).
      High HSP90 expression was associated with earlier tumor stages (p = 0.019),
      absence of lymph node (p = 0.006), and absence of distant metastases (p = 0.001).
      Patients with high tumoral HSP90 levels had a better survival (p = 0.032), but
      this was not independent from other prognostic relevant pathologic parameters.
      Her2 expression was not associated with any of the investigated
      histopathological, molecular, or clinical parameters. CONCLUSIONS: High HSP90
      levels are reflecting lower malignant potential in colon cancer. Her2 positivity
      can be observed in a small number of cases. Targeting HSP90 and/or Her2 may be an
      alternative therapeutic approach in colon cancer in a subset of patients.

PMID- 24733428
TI  - Strategies for improving participation in diabetes education. A qualitative
      study.
AB  - OBJECTIVE: Diabetes mellitus is highly prevalent and can lead to serious
      complications and mortality. Patient education can help to avoid negative
      outcomes, but up to half of the patients do not participate. The aim of this
      study was to analyze patients' attitudes towards diabetes education in order to
      identify barriers to participation and develop strategies for better patient
      education. METHODS: We conducted a qualitative study. Seven GP practices were
      purposively selected based on socio-demographic data of city districts in
      Hamburg, Germany. Study participants were selected by their GPs in order to
      increase participation. Semi-structured face-to-face interviews were conducted
      with 14 patients. Interviews were audiotaped and transcribed verbatim. The sample
      size was determined by data saturation. Data were analysed by qualitative content
      analysis. Categories were determined deductively and inductively. RESULTS: The
      interviews yielded four types of barriers: 1) Statements and behaviour of the
      attending physician influence the patients' decisions about diabetes education.
      2) Both, a good state of health related to diabetes and physical/psychosocial
      comorbidity can be reasons for non-participation. 3) Manifold motivational
      factors were discussed. They ranged from giving low priority to diabetes to
      avoidance of implications of diabetes education as being confronted with illness
      narratives of others. 4) Barriers also include aspects of the patients' knowledge
      and activity. CONCLUSIONS: First, physicians should encourage patients to
      participate in diabetes education and argue that they can profit even if actual
      treatment and examination results are promising. Second, patients with other
      priorities, psychic comorbidity or functional limitations might profit more from
      continuous individualized education adapted to their specific situation instead
      of group education. Third, it might be justified that patients do not participate
      in diabetes education if they have slightly increased blood sugar values only and
      no risk for harmful consequences or if they already have sufficient knowledge on
      diabetes.

PMID- 24733429
TI  - Basal cell carcinoma: an evidence-based treatment update.
AB  - BACKGROUND: Basal cell carcinoma (BCC) is the most common skin cancer. Surgical
      excision remains the standard of treatment, but several alternative treatment
      modalities exist. OBJECTIVES: This review aims to provide a current analysis of
      evidence for the treatment of BCC; specifically, which treatments have the lowest
      recurrence rates and the best cosmetic outcomes. METHODS: We searched PubMed
      (January 1946 to August 2013), Ovid MEDLINE (2003-August 2013), the Cochrane
      Central Register of Controlled Trials (January 1993 to August 2013), and the
      Cochrane Database of Systematic Reviews (The Cochrane Library Issue 9, 2013)
      databases for randomized controlled trials, systematic reviews, or comparative
      studies for the treatment of BCC. RESULTS: We found 615 potential articles. Two
      independent reviewers selected 40 studies: 29 randomized controlled trials
      (RCTs), seven systematic reviews, and four nonrandomized prospective trials.
      Treatment modalities reviewed include surgical therapy, radiotherapy and
      cryotherapy, photodynamic therapy (PDT), topical imiquimod, topical 5
      fluorouracil (5-FU), topical solasodine glycoalkaloids, topical ingenol mebutate,
      intralesional 5-FU, intralesional interferon (IFN), and oral hedgehog pathway
      inhibitors. CONCLUSIONS: The available data suggest that surgical methods remain
      the gold standard in BCC treatment, with Mohs micrographic surgery typically
      utilized for high-risk lesions. Suitable alternate treatment options for
      appropriately selected primary low-risk lesions may include PDT, cryotherapy,
      topical imiquimod, and 5-FU. Radiotherapy is a suitable alternate for surgical
      methods for treatment in older patient populations. Electrodesiccation and
      curettage (ED&C) is a commonly used primary treatment option for low-risk
      lesions; however, there were no RCTs examining ED&C that met our inclusion
      criteria. New hedgehog pathway inhibitors are promising for the management of
      advanced BCC; however, side effects are a concern for some patients, and much
      remains to be learned regarding optimal treatment length, risk of recurrence, and
      potential development of resistance. There is insufficient evidence at present to
      make recommendations on topical solasodine glycoalkaloids, topical ingenol
      mebutate, and intralesional 5-FU and IFN-alpha. Overall continued research on the
      efficacy of treatment modalities is needed. In particular, studies should include
      histologic ascertainment of clearance, long-term follow-up, stratification based
      on tumor subtype, and comparison with surgical outcomes.

PMID- 24733431
TI  - Chiral/ring closed vs. achiral/open chain triazine-based organogelators:
      induction and amplification of supramolecular chirality in organic gels.
AB  - The purpose of this study is to compare the gelling behavior of two molecules: a
      chiral compound and its achiral counterpart. The chiral partner is characterized
      by a rigid, chiral pyrrolidine nucleus, while the achiral one contains a flexible
      diethanolamine moiety. The chiral compound is an already known good
      organogelator, but also the achiral compound shows remarkable gelling properties.
      Very interestingly, a small fraction of the chiral compound induces chirality and
      strong CD effects in its aggregates with the achiral one. The observed chirality
      amplification corresponds to a peculiar sergeant-and-soldier effect. Molecular
      modelling and CD calculations suggested a model for the supramolecular assembly
      of hetero-aggregates that fits the experimental data. 

PMID- 24733432
TI  - Crystal structure of truncated haemoglobin from an extremely thermophilic and
      acidophilic bacterium.
AB  - A truncated haemoglobin (tHb) has been identified in an acidophilic and
      thermophilic methanotroph Methylacidiphilium infernorum. Hell's Gate Globin IV
      (HGbIV) and its related tHbs differ from all other bacterial tHbs due to their
      distinctively large sequence and polar distal haem pocket residues. Here we
      report the crystal structure of HGbIV determined at 1.96 A resolution. The HGbIV
      structure has the distinctive 2/2 alpha-helical structure with extensions at both
      termini. It has a large distal site cavity in the haem pocket surrounded by four
      polar residues: His70(B9), His71(B10), Ser97(E11) and Trp137(G8). This cavity can
      bind bulky ligands such as a phosphate ion. Conformational shifts of His71(B10),
      Leu90(E4) and Leu93(E7) can also provide more space to accommodate larger ligands
      than the phosphate ion. The entrance/exit of such bulky ligands might be
      facilitated by positional flexibility in the CD1 loop, E helix and haem
      propionate A. Therefore, the large cavity in HGbIV with polar His70(B9) and
      His71(B10), in contrast to the distal sites of other bacterial tHbs surrounded by
      non-polar residues, suggests its distinct physiological functions. 

PMID- 24733433
TI  - Exchange kinetics by inversion transfer: integrated analysis of the phosphorus
      metabolite kinetic exchanges in resting human skeletal muscle at 7 T.
AB  - PURPOSE: To develop an inversion pulse-based, chemical exchange saturation
      transfer-like method for detection of (31) P magnetization exchanges among all
      nuclear magnetic resonance visible metabolites suitable for providing an
      integrated kinetic analysis of phosphorus exchange reactions in vivo. METHODS:
      The exchange kinetics by inversion transfer (EKIT) sequence includes application
      of a frequency-selective inversion pulse arrayed over the range of relevant (31)
      P frequencies, followed by a constant delay and a hard readout pulse. A series of
      EKIT spectra, each given by a plot of Z-magnetization for each metabolite of
      interest versus frequency of the inversion pulse, can be generated from this
      single data set. RESULTS: EKIT spectra reflect chemical exchange due to known
      biochemical reactions, cross-relaxation effects, and relayed magnetization
      transfers due to both processes. The rate constants derived from EKIT data
      collected on resting human skeletal muscle were: ATP synthesis via ATP synthase
      (0.050 +/- 0.016 s(-1) ), ATP synthesis via creatine kinase (0.264 +/- 0.023 s(
      1) ), and cross-relaxation between neighboring spin pairs within ATP (0.164 +/-
      0.022 s(-1) ). CONCLUSION: EKIT provides a simple, alternative method to detect
      chemical exchange, cross relaxation, and relayed magnetization transfer effects
      in human skeletal muscle at 7 T.

PMID- 24733434
TI  - Strategies in the design of small-molecule fluorescent probes for peptidases.
AB  - Peptidases, which can cleave specific peptide bonds in innumerable categories of
      substrates, usually present pivotal positions in protein activation, cell
      signaling and regulation as well as in the origination of amino acids for protein
      generation or application in other metabolic pathways. They are also involved in
      many pathological conditions, such as cancer, atherosclerosis, arthritis, and
      neurodegenerative disorders. This review article aims to conduct a wide-ranging
      survey on the development of small-molecule fluorescent probes for peptidases, as
      well as to realize the state of the art in the tailor-made probes for diverse
      types of peptidases. 

PMID- 24733435
TI  - Improved performance of a polymer nanogenerator based on silver nanoparticles
      doped electrospun P(VDF-HFP) nanofibers.
AB  - We report on the electrospinning of poly(vinylidene fluoride-hexafluoropropylene)
      [P(VDF-HFP)] nanofibers doped with silver nanoparticles for the preparation of a
      polymer based nanogenerator (PNG). It has been found that the yield of the
      piezoelectric phase is increased by the addition of silver nanoparticles.
      Furthermore, defects in the P(VDF-HFP) electrospun fibers are removed resulting
      in a significant enhancement in the output power of the PNG. A maximum generated
      PNG output voltage of 3 V with a current density of 0.9 MUA cm(-2) is achieved. 

PMID- 24733436
TI  - Biomonitoring of air pollution with mercury in Croatia by using moss species and
      CV-AAS.
AB  - Moss samples from four dominant species (Hypnum cupressiforme, Pleurozium
      schreberi, Homalothecium sericeum and Brachythecium rutabulum) were collected
      during the summer and autumn of 2010 from 121 sampling sites evenly distributed
      over the territory of Croatia. Samples were totally digested by using microwave
      digestion system, whilst mercury was analysed by using cold vapour atomic
      absorption spectrometry (CV-AAS). Descriptive statistics were done from analyses
      of mercury in all moss samples. The content of mercury ranged from 0.010 to 0.145
      mg kg(-1) with a median value of 0.043 mg kg(-1). Hg distribution map shows the
      sites of the country with higher levels of this element. High contents of Hg were
      found in moss samples collected from the regions of Podravina and Istria as a
      result of anthropogenic pollution. Comparison of median values and ranges with
      those found in moss samples in 2006 shows slight reduction of mercury air
      pollution. When compared to the results obtained from recent studies conducted in
      Slovenia, Macedonia and especially in Norway-which serves as a reference
      considering the fact that it is a pristine area-mercury air pollution in Croatia
      is insignificant. 

PMID- 24733437
TI  - A comparative study on the decomposition of edible and non-edible oil cakes in
      the Gangetic alluvial soil of West Bengal.
AB  - An experiment has been conducted under laboratory conditions to investigate the
      effect of decomposition of two edible oil cakes, viz. mustard cake (Brassica
      juncea L) and groundnut cake (Arachis hypogaea L), and two non-edible oil cakes,
      viz. mahua cake (Madhuca indica Gmel) and neem cake (Azadirachta indica Juss), at
      the rate of 5.0 t ha(-1) on the changes of microbial growth and activities in
      relation to transformations and availability of some plant nutrients in the
      Gangetic alluvial (Typic Haplustept) soil of West Bengal, India. Incorporation of
      oil cakes, in general, highly induced the proliferation of total bacteria,
      actinomycetes, and fungi, resulting in greater retention and availability of
      oxidizable C, N, and P in soil. As compared to untreated control, the highest
      stimulation of total bacteria and actinomycetes was recorded with mustard cake
      (111.9 and 84.3 %, respectively) followed by groundnut cake (50.5 and 52.4 %,
      respectively), while the fungal colonies were highly accentuated due to the
      incorporation of neem cake (102.8 %) in soil. The retention of oxidizable organic
      C was highly increased due to decomposition of non-edible oil cakes, more so
      under mahua cake (14.5 %), whereas edible oil cakes and groundnut cake in
      particular exerted maximum stimulation (16.7 %) towards the retention of total N
      in soil. A similar trend was recorded towards the accumulation of available
      mineral N in soil and this was more pronounced with mustard cake (45.6 %) for
      exchangeable NH4 (+) and with groundnut cake (63.9 %) for soluble NO3 (-). The
      highest retention of total P (46.9 %) was manifested by the soil when it was
      incorporated with neem cake followed by the edible oil cakes; while the available
      P was highly induced due to the addition of edible oil cakes, the highest being
      under groundnut cake (23.5 %) followed by mustard cake (19.6 %). 

PMID- 24733438
TI  - Indirect magnetic resonance imaging lymphography identifies lymph node metastasis
      in rabbit pyriform sinus VX2 carcinoma using ultra-small super-paramagnetic iron
      oxide.
AB  - BACKGROUND: USPIO is a contrast agent for MRI that can generate T2W images with
      low signal intensities. After subcutaneous or intravenous injection of USPIO,
      normal lymph node tissues uptake these nano-particles, but tumor cells do not.
      Thus, tumor metastasis can be detected using this contrast agent. OBJECTIVE: The
      aim of this study was to access the feasibility of USPIO enhanced MRI for the
      detection of cervical lymph node metastasis in a pyriform sinus carcinoma animal
      model and to investigate the ability of USPIO to enhance images of cervical lymph
      node metastases. METHODS AND FINDINGS: Twenty New Zealand rabbits were randomly
      divided into tumor and inflammatory groups, and each group contained 10 rabbits.
      In the inflammatory group, a 0.5 ml egg yolk emulsion was injected into the sub
      mandibular muscle of the rabbits to induce an inflammatory reaction in their
      cervical lymph nodes. In the tumor group, a VX2 tumor tissue suspension was
      transplanted into the pyriform sinus sub-mucosa of the rabbits using direct
      laryngoscope. Four weeks after the tumor or egg yolk injection, MRIs were
      performed before and after USPIO injection to observe the imaging enhancement
      features of USPIO. After that, a histo-pathological analysis was performed for
      all rabbits. We found the metastatic lymph nodes had no signal reduced intensity
      or irregular signal reduced intensity on T2-weighted image by using USPIO
      enhancement. In the tumor group,the sensitivity and specificity of plain MRI were
      57.6% and 60.7%. The corresponding values of USPIO-enhanced MRl were 96.1% and
      85.7%. (P<0.05). CONCLUSION: The features and the extent of the lymph node
      metastases corresponded to those observed on USPIO-enhanced MR images. USPIO
      enhanced MRI is useful for the detection and estimation of lymph node metastasis
      in this cervical carcinoma animal model.

PMID- 24733439
TI  - Valproate-induced liver injury: modulation by the omega-3 fatty acid DHA proposes
      a novel anticonvulsant regimen.
AB  - BACKGROUND: The polyunsaturated, omega-3 fatty acid, docosahexaenoic acid (DHA),
      claims diverse cytoprotective potentials, although via largely undefined
      triggers. Thus, we currently first tested the ability of DHA to ameliorate
      valproate (VPA)-evoked hepatotoxicity, to modulate its anticonvulsant effects,
      then sought the cellular and molecular basis of such actions. Lastly, we also
      verified whether DHA may kinetically alter plasma levels/clearance rate of VPA.
      METHODS AND RESULTS: VPA (500 mg/kg orally for 14 days in rats) evoked prominent
      hepatotoxicity that appeared as a marked rise (2- to 4-fold) in serum hepatic
      enzymes (gamma-glutamyl transferase [gamma-GT], alanine aminotransferase [ALT],
      and alkaline phosphatase [ALP]), increased hepatic lipid peroxide (LPO) and tumor
      necrosis factor-alpha (TNFalpha) levels, as well as myeloperoxidase (MPO)
      activity (3- to 5-fold), lowering of serum albumin (40 %), and depletion of liver
      reduced-glutathione (GSH, 35 %). Likewise, histopathologic examination revealed
      hepatocellular degeneration, replacement by inflammatory cells, focal pericentral
      necrosis, and micro/macrovesicular steatosis. Concurrent treatment with DHA (250
      mg/kg) markedly blunted the elevated levels of liver enzymes, lipid peroxides,
      TNFalpha, and MPO activity, while raising serum albumin and hepatic GSH levels.
      DHA also alleviated most of the cytologic insults linked to VPA. Besides, in a
      pentylenetetrazole (PTZ) mouse convulsion model, DHA (250 mg/kg) markedly
      increased the latency in convulsion evoked by VPA, beyond their individual
      responses. Lastly, pharmacokinetic studies revealed that joint DHA administration
      did not alter serum VPA concentrations. CONCLUSIONS: DHA substantially
      ameliorated liver injury induced by VPA, while also markedly boosted its
      pharmacologic effects. DHA manipulated definite cellular machinery to curb liver
      oxidative stress and inflammation, without affecting VPA plasma levels.
      Collectively, these protective and synergy profiles for DHA propose a superior
      VPA-drug combination regimen.

PMID- 24733440
TI  - Aqueous worm gels can be reconstituted from freeze-dried diblock copolymer
      powder.
AB  - Worm-like diblock copolymer nanoparticles comprising poly(glycerol
      monomethacrylate) (PGMA) as a stabilizer block and poly(2-hydroxypropyl
      methacrylate) (PHPMA) as a core-forming block were readily synthesized at 10% w/w
      solids via aqueous dispersion polymerization at 70  degrees C using Reversible
      Addition-Fragmentation chain Transfer (RAFT) chemistry. On cooling to 20  degrees
      C, soft transparent free-standing gels are formed due to multiple inter-worm
      interactions. These aqueous PGMA-PHPMA diblock copolymer worms were freeze-dried,
      then redispersed in water with cooling to 3-5  degrees C before warming up to 20 
      degrees C; this protocol ensures molecular dissolution of the copolymer chains,
      which aids formation of a transparent aqueous gel. Rheology, SAXS and TEM studies
      confirm that such reconstituted gels comprise formed PGMA-PHPMA copolymer worms
      and they possess essentially the same physical properties determined for the
      original worm gels prior to freeze-drying. Such worm gel reconstitution is
      expected to be highly beneficial in the context of various biomedical
      applications, since it enables worm gels to be readily prepared using a wide
      range of cell growth media as the continuous aqueous phase. 

PMID- 24733441
TI  - Genome-wide association for growth traits in Canchim beef cattle.
AB  - Studies are being conducted on the applicability of genomic data to improve the
      accuracy of the selection process in livestock, and genome-wide association
      studies (GWAS) provide valuable information to enhance the understanding on the
      genetics of complex traits. The aim of this study was to identify genomic regions
      and genes that play roles in birth weight (BW), weaning weight adjusted for 210
      days of age (WW), and long-yearling weight adjusted for 420 days of age (LYW) in
      Canchim cattle. GWAS were performed by means of the Generalized Quasi-Likelihood
      Score (GQLS) method using genotypes from the BovineHD BeadChip and estimated
      breeding values for BW, WW, and LYW. Data consisted of 285 animals from the
      Canchim breed and 114 from the MA genetic group (derived from crossings between
      Charolais sires and 1/2 Canchim + 1/2 Zebu dams). After applying a false
      discovery rate correction at a 10% significance level, a total of 4, 12, and 10
      SNPs were significantly associated with BW, WW, and LYW, respectively. These SNPs
      were surveyed to their corresponding genes or to surrounding genes within a
      distance of 250 kb. The genes DPP6 (dipeptidyl-peptidase 6) and CLEC3B (C-type
      lectin domain family 3 member B) were highlighted, considering its functions on
      the development of the brain and skeletal system, respectively. The GQLS method
      identified regions on chromosome associated with birth weight, weaning weight,
      and long-yearling weight in Canchim and MA animals. New candidate regions for
      body weight traits were detected and some of them have interesting biological
      functions, of which most have not been previously reported. The observation of
      QTL reports for body weight traits, covering areas surrounding the genes (SNPs)
      herein identified provides more evidence for these associations. Future studies
      targeting these areas could provide further knowledge to uncover the genetic
      architecture underlying growth traits in Canchim cattle. 

PMID- 24733442
TI  - Anti-laminin-gamma1 pemphigoid developed in a case of autosomal recessive
      congenital ichthyosis.

PMID- 24733444
TI  - Veterans' perceptions of behavioral health care in the veterans health
      administration: a national survey.
AB  - OBJECTIVE: This study provided national estimates of perceptions of behavioral
      health care services among patients of the Veterans Health Administration (VHA)
      with a diagnosis of bipolar I disorder, major depression, posttraumatic stress
      disorder, schizophrenia, or substance use disorder. METHODS: A stratified random
      sample of 6,190 patients completed telephone interviews from November 2008
      through August 2009. Patients (N=5,185) who reported receiving VHA behavioral
      health care in the prior 12 months were asked about their need for housing and
      employment services, timeliness and recovery orientation of their care,
      satisfaction with care, and perceived improvement. RESULTS: Half of patients
      reported always receiving routine appointments as soon as requested, and 42% were
      highly satisfied with their VHA mental health care. Approximately 74% of patients
      reported being helped by the treatment they received, yet only 32% reported that
      their symptoms had improved. After controlling for covariates, the analyses
      showed that patients with a substance use disorder reported lower satisfaction
      with care and perceived their treatment to be less helpful compared with patients
      without a substance use disorder. CONCLUSIONS: Although matched sample comparison
      data were not available, the results showed that overall patient perceptions of
      VHA mental health care were favorable, but there was significant room for
      improvement across all areas of assessment. A majority reported being helped by
      treatment, but few reported symptom improvement. Variations in perceptions among
      patients with different disorders suggest the potential importance of psychiatric
      diagnosis, particularly substance use disorder, in assessing patient perceptions
      of care.

PMID- 24733445
TI  - Does a torsion adapter improve functional mobility, pain, and fatigue in patients
      with transtibial amputation?
AB  - BACKGROUND: Turning gait is an integral part of daily ambulation and likely poses
      a greater challenge for patients with transtibial amputation compared with
      walking a straight pathway. A torsion adapter is a prosthetic component that can
      increase transverse plane compliance of the prosthesis and decrease the torque
      applied to the residual limb, but whether this will improve patients' mobility,
      pain, and fatigue remains unknown. QUESTIONS/PURPOSES: Does prescription of a
      torsion adapter translate to improvements in (1) functional mobility and (2) self
      perceived pain and fatigue in moderately active patients with lower limb
      amputation? METHODS: Ten unilateral transtibial amputees wore a torsion or rigid
      adapter in random order. Functional mobility was assessed through a field
      measurement using an activity monitor and through a laboratory measurement using
      a 6-minute walk test that included turns. The residual limb pain grade assessed
      self-perceived pain and the Multidimensional Fatigue Inventory assessed fatigue.
      RESULTS: We found relatively small functional differences for amputees wearing a
      torsion adapter versus a rigid adapter. Amputees wearing a torsion adapter tended
      to take more low- and medium-intensity steps per day (331 +/- 365 and 437 +/- 511
      difference in steps; effect size = 0.44 and 0.17; confidence interval [CI], 70
      592 and 71-802; p = 0.019 and 0.024, respectively). They also experienced less
      pain interference with activities (1.9 +/- 1.7 change in score; effect size =
      0.83; CI, 0.3-3.4; p = 0.026) when wearing a torsion adapter. However, these
      patients took a similar number of total steps per day, walked a comparable
      distance in 6 minutes, and reported similar residual limb pain and fatigue.
      CONCLUSIONS: For a moderately active group of amputees, the torsion adapter did
      not translate to substantial improvements in functional mobility and self
      perceived pain and fatigue. The small increases in low- and medium-intensity
      activities with less pain interference when wearing a torsion adapter provides
      evidence to support prescribing this device for amputees with difficulty
      navigating the household and community environments.

PMID- 24733446
TI  - Hospital readmissions after surgical treatment of proximal humerus fractures: is
      arthroplasty safer than open reduction internal fixation?
AB  - BACKGROUND: With technologic advances such as locked periarticular plating,
      hemiarthroplasty of the humeral head, and more recently reverse total shoulder
      replacement, surgical treatment of proximal humerus fractures has become more
      commonplace. However, there is insufficient information regarding patient
      outcomes after surgery, such as the frequency of unplanned hospital readmissions
      and factors contributing to readmission. QUESTIONS/PURPOSES: We measured (1) the
      frequency of unplanned hospital readmissions after surgical treatment of proximal
      humerus fractures, (2) the medical and surgical causes of readmission, and (3)
      the risk factors associated with unplanned readmissions. METHODS: The State
      Inpatient Database from seven different states was used to identify patients who
      underwent treatment for a proximal humerus fracture with open reduction and
      internal fixation (ORIF), hemiarthroplasty of the humeral head, or reverse total
      shoulder arthroplasty from 2005 through 2010. The database was used to measure
      the 30-day and 90-day readmission rates and identify causes and risk factors for
      readmission. Multivariate modeling and a Cox proportional hazards model were used
      for statistical analysis. RESULTS: A total of 27,017 patients were included with
      an overall 90-day readmission rate of 14% (15% for treatment with ORIF, 15% for
      reverse total shoulder arthroplasty, and 13% for hemiarthroplasty). The majority
      of readmissions were associated with medical diagnoses (75%), but treatment with
      ORIF was associated with the most readmissions from surgical complications, (29%)
      followed by reverse total shoulder arthroplasty (20%) and hemiarthroplasty (16%)
      (p < 0.001). Risk of readmission was greater for patients who were female,
      African American, discharged to a nursing facility, or had Medicaid insurance.
      CONCLUSIONS: As the majority of unplanned hospital readmissions were associated
      with medical diagnoses, it is important to consider patient medical comorbidities
      before surgical treatment of proximal humerus fractures and during the
      postoperative care phase. LEVEL OF EVIDENCE: Level III, therapeutic study. See
      the Instructions for Authors for a complete description of levels of evidence.

PMID- 24733447
TI  - Screening for deep vein thrombosis after periacetabular osteotomy in adult
      patients: is it necessary?
AB  - BACKGROUND: The periacetabular osteotomy has become a common procedure for
      treating symptomatic acetabular dysplasia. Like other major hip procedures, there
      is concern regarding the risk of associated venous thromboembolic disease.
      Nevertheless, there is limited information regarding the need for screening, and
      optimal prophylactic measures have not been established. QUESTIONS/PURPOSES: We
      sought to determine the frequency of thromboembolic events (deep vein thrombosis
      [DVT] and symptomatic pulmonary embolism [PE]) associated with the periacetabular
      osteotomy in in patients receiving aspirin and mechanical compression
      prophylaxis. METHODS: We performed a retrospective review of 134 adult patients
      (149 hips) treated with the periacetabular osteotomy during an 8-year period.
      During this period, 136 (91%) of the hips treated with a periacetabular osteotomy
      were screened within 1 week for DVT, whereas 13 (9%) could not be evaluated for
      various reasons. The mean age of the patients at the time of surgery was 30 years
      (range, 18-60 years), and no patients were lost to followup during the 4 to 6
      months after surgery. The same thromboembolic prophylactic regimen was used for
      all patients. This consisted of 325 mg aspirin twice a day and compression
      stockings for 6 weeks and lower extremity pneumatic compression devices while
      hospitalized. Screening bilateral lower extremity ultrasonography was performed
      within 1 week (mean, 4 days) of the procedure to detect asymptomatic DVTs.
      RESULTS: Of the 134 patients, two patients (two hips) with negative postoperative
      screening ultrasounds presented at 14 and 38 days postoperatively with clinical
      symptoms of DVT. Repeat ultrasound confirmed this diagnosis in both cases. There
      were no symptoms of PE. Screening venous ultrasonography did not identify any
      DVTs during the early postoperative period before discharge. These two patients
      were treated with 3 to 6 months of warfarin anticoagulation. Neither patient had
      persistent symptoms related to the DVT. CONCLUSIONS: These data indicate that the
      risk of symptomatic DVT associated with periacetabular osteotomy is low (1%) with
      use of aspirin and mechanical compression prophylaxis. Furthermore, routine
      postoperative screening did not detect any patients with an asymptomatic DVT.
      LEVEL OF EVIDENCE: Level IV, therapeutic study. See the Instructions for Authors
      for a complete description of levels of evidence.

PMID- 24733449
TI  - Polished trays reduce backside wear independent of post location in posterior
      stabilized TKAs.
AB  - BACKGROUND: Backside damage of the polyethylene in TKA is a potential source of
      debris. The location of the tibial post in posterior-stabilized implants may
      influence micromotion, and thus affect backside damage, as may surface roughness.
      QUESTIONS: We used implant retrieval analysis to (1) examine if there were
      differences in backside damage among three modern posterior-stabilized implants
      attributable to variable surface roughness; (2) determine if the location of
      damage on the tibial post affected the pattern of backside damage; and (3)
      determine if demographics influenced backside damage. METHODS: We identified 403
      posterior-stabilized tibial retrieved inserts (147 NexGen((r)), 152
      Optetrak((r)), 104 Genesis((r)) II). The damage on the surfaces of the tibial
      posts was previously graded. The backside of the inserts (divided into quadrants)
      were scored for evidence of damage. The total quadrant damage was compared for
      each implant group, the relationship between post face damage and location of
      damage on the backside was determined for each implant group, and total backside
      damage was compared among the three implant groups. RESULTS: No correlation was
      found between the location of damage on the post and location of damage on the
      backside of the implant for any of the three groups. The Genesis((r)) II
      polyethylene implants, which articulate with a highly polished tibial tray,
      showed a significantly lower total backside damage score (p < 0.01) when compared
      with the other two implant groups. The Genesis((r)) II and Optetrak((r)) showed
      significantly more damage in the posterior quadrants of the implants (p < 0.01)
      when compared with the anterior quadrants. A linear regression analysis revealed
      that lower tibial tray surface roughness was correlated with decreased damage.
      CONCLUSIONS: An implant design with a highly polished tibial tray was associated
      with decreased backside damage. However, tibial post design and location did not
      influence the location of backside damage. CLINICAL RELEVANCE: Our study showed
      that a highly polished tibial tray was associated with decreased damage to the
      backside of polyethylene inserts independent of post design and location. These
      findings should be taken into consideration when new generations of implants are
      designed.

PMID- 24733450
TI  - CORR Insights(r): High satisfaction yet decreased activity 4 years after
      transphyseal ACL reconstruction.

PMID- 24733451
TI  - Aspects and assessment of delirium in old age. First data from a German
      interdisciplinary emergency department.
AB  - BACKGROUND: The prevalence of delirium in hospitalized patients is high, but
      delirium is frequently not identified by treating physicians in emergency
      departments (EDs). Although the number of elderly patients admitted to EDs is
      increasing, no data on prevalence, identification and outcome of delirious
      elderly patients in German EDs exist. OBJECTIVES: To evaluate the prevalence and
      identification of delirium in elderly patients in a German ED and to identify
      characteristics of delirium in elderly ED patients. METHODS: Evaluation of data
      from a prospective single-center observational study. The study was conducted in
      the interdisciplinary ED of an urban university-affiliated hospital receiving
      approximately 80,000 visits per year. The shortened Confusion Assessment Method
      (CAM) was used to screen 133 consecutive ED patients, aged 75 years and older,
      for delirium. Comorbid conditions were ascertained by patient interview and
      review of medical records. Data concerning patient mortality and current living
      status were collected 28 days after the ED visit in a structured telephone
      interview. RESULTS: A positive CAM result was recorded in 14.3 % of cases; 68.4 %
      of these CAM-positive patients were not identified as being delirious by the ED
      physician. The 28-day mortality was higher among patients with delirium.
      Dependency on external help, polypharmacy, pre-existing cognitive or mobility
      impairments and the presence of any care level were strongly associated with
      delirium. CONCLUSION: Elderly patients with known risk factors should be
      routinely assessed for delirium in the ED with a standardized assessment tool
      such as the CAM.

PMID- 24733453
TI  - An unusual cause of dysphagia.

PMID- 24733454
TI  - Methods for the preparation of large quantities of complex single-stranded
      oligonucleotide libraries.
AB  - Custom-defined oligonucleotide collections have a broad range of applications in
      fields of synthetic biology, targeted sequencing, and cytogenetics. Also, they
      are used to encode information for technologies like RNA interference, protein
      engineering and DNA-encoded libraries. High-throughput parallel DNA synthesis
      technologies developed for the manufacture of DNA microarrays can produce
      libraries of large numbers of different oligonucleotides, but in very limited
      amounts. Here, we compare three approaches to prepare large quantities of single
      stranded oligonucleotide libraries derived from microarray synthesized
      collections. The first approach, alkaline melting of double-stranded PCR
      amplified libraries with a biotinylated strand captured on streptavidin coated
      magnetic beads results in little or no non-biotinylated ssDNA. The second method
      wherein the phosphorylated strand of PCR amplified libraries is nucleolyticaly
      hydrolyzed is recommended when small amounts of libraries are needed. The third
      method combining in vitro transcription of PCR amplified libraries to reverse
      transcription of the RNA product into single-stranded cDNA is our recommended
      method to produce large amounts of oligonucleotide libraries. Finally, we propose
      a method to remove any primer binding sequences introduced during library
      amplification. 

PMID- 24733455
TI  - Dissolution of NaCl nanocrystals: an ab initio molecular dynamics study.
AB  - The dissolution of NaCl has been systematically investigated by employing ab
      initio molecular dynamics (AIMD) on different NaCl nanocrystals as well as on a
      surface system immersed in water. We discovered a complex dissolution process
      simultaneously involving multiple ions initiated at the corner sites of the
      crystal. Our simulations indicated a difference in the dissolution rates of
      sodium and chlorine. While sodiums readily became partially solvated, chlorines
      more frequently transitioned into the fully solvated state leading to an overall
      greater dissolution rate for Cl. We determined that this difference arises due to
      faster water mediated elongations of individual ionic bonds to Na, but a
      significantly slower process for the last bond in comparison to Cl. In an attempt
      to investigate this phenomenon further, we performed metadynamics based free
      energy simulations on a surface slab presenting corner sites similar to those in
      cubic crystals, aiming to extract the dissolution free energy profile of corner
      ions. In qualitative agreement with the nanocrystal simulations, this revealed a
      shallower first free energy minimum for Na, but no statistically significant
      difference in the corresponding barriers and inconclusive results for the latter
      stage. Finally, simulations of smaller NaCl crystals illustrated how dissolution
      proceeds beyond the point of crystal lattice collapse, highlighting the strength
      of solvated ion interactions. 

PMID- 24733457
TI  - Quantification of cerebral perfusion using dynamic quantitative susceptibility
      mapping.
AB  - PURPOSE: The purpose of this study is to develop a dynamic quantitative
      susceptibility mapping (QSM) technique with sufficient temporal resolution to map
      contrast agent concentration in cerebral perfusion imaging. METHODS: The dynamic
      QSM used a multiecho three-dimensional (3D) spoiled gradient echo golden angle
      interleaved spiral sequence during contrast bolus injection. Four-dimensional
      (4D) space-time resolved magnetic field reconstruction was performed using the
      temporal resolution acceleration with constrained evolution reconstruction
      method. Deconvolution of the gadolinium-induced field was performed at each time
      point with the morphology enabled dipole inversion method to generate a 4D
      gadolinium concentration map, from which three-dimensional spatial distributions
      of cerebral blood volume and cerebral blood flow were computed. RESULTS: Initial
      in vivo brain imaging demonstrated the feasibility of using dynamic QSM for
      generating quantitative 4D contrast agent maps and imaging three-dimensional
      perfusion. The cerebral blood flow obtained with dynamic QSM agreed with that
      obtained using arterial spin labeling. CONCLUSION: Dynamic QSM can be used to
      perform 4D mapping of contrast agent concentration in contrast-enhanced magnetic
      resonance imaging. The perfusion parameters derived from this 4D contrast agent
      concentration map were in good agreement with those obtained using arterial spin
      labeling.

PMID- 24733456
TI  - Molecular network analysis enhances understanding of the biology of mental
      disorders.
AB  - We provide an introduction to network theory, evidence to support a connection
      between molecular network structure and neuropsychiatric disease, and examples of
      how network approaches can expand our knowledge of the molecular bases of these
      diseases. Without systematic methods to derive their biological meanings and
      inter-relatedness, the many molecular changes associated with neuropsychiatric
      disease, including genetic variants, gene expression changes, and protein
      differences, present an impenetrably complex set of findings. Network approaches
      can potentially help integrate and reconcile these findings, as well as provide
      new insights into the molecular architecture of neuropsychiatric diseases.
      Network approaches to neuropsychiatric disease are still in their infancy, and we
      discuss what might be done to improve their prospects. 

PMID- 24733458
TI  - Importance of multidrug efflux pumps in the antimicrobial resistance property of
      clinical multidrug-resistant isolates of Neisseria gonorrhoeae.
AB  - The contribution of drug efflux pumps in clinical isolates of Neisseria
      gonorrhoeae that express extensively drug-resistant or multidrug-resistant
      phenotypes has heretofore not been examined. Accordingly, we assessed the effect
      on antimicrobial resistance of loss of the three gonococcal efflux pumps
      associated with a known capacity to export antimicrobials (MtrC-MtrD-MtrE, MacA
      MacB, and NorM) in such clinical isolates. We report that the MIC of several
      antimicrobials, including seven previously and currently recommended for
      treatment was significantly impacted. 

PMID- 24733459
TI  - Very-high-dose caspofungin combined with voriconazole to treat central nervous
      system aspergillosis: substantial penetration of caspofungin into cerebrospinal
      fluid.

PMID- 24733460
TI  - Predictive models for identification of hospitalized patients harboring KPC
      producing Klebsiella pneumoniae.
AB  - The production of Klebsiella pneumoniae carbapenemases (KPCs) by
      Enterobacteriaceae has become a significant problem in recent years. To identify
      factors that could predict isolation of KPC-producing K. pneumoniae (KPCKP) in
      clinical samples from hospitalized patients, we conducted a retrospective,
      matched (1:2) case-control study in five large Italian hospitals. The case cohort
      consisted of adult inpatients whose hospital stay included at least one
      documented isolation of a KPCKP strain from a clinical specimen. For each case
      enrolled, we randomly selected two matched controls with no KPCKP-positive
      cultures of any type during their hospitalization. Matching involved hospital,
      ward, and month/year of admission, as well as time at risk for KPCKP isolation. A
      subgroup analysis was also carried out to identify risk factors specifically
      associated with true KPCKP infection. During the study period, KPCKP was isolated
      from clinical samples of 657 patients; 426 of these cases appeared to be true
      infections. Independent predictors of KPCKP isolation were recent admission to an
      intensive care unit (ICU), indwelling urinary catheter, central venous catheter
      (CVC), and/or surgical drain, >= 2 recent hospitalizations, hematological cancer,
      and recent fluoroquinolone and/or carbapenem therapy. A Charlson index of >= 3,
      indwelling CVC, recent surgery, neutropenia, >= 2 recent hospitalizations, and
      recent fluoroquinolone and/or carbapenem therapy were independent risk factors
      for KPCKP infection. Models developed to predict KPCKP isolation and KPCKP
      infection displayed good predictive power, with the areas under the receiver
      operating characteristic curves of 0.82 (95% confidence interval [CI], 0.80 to
      0.84) and 0.82 (95% CI, 0.80 to 0.85), respectively. This study provides novel
      information which might be useful for the clinical management of patients
      harboring KPCKP and for controlling the spread of this organism.

PMID- 24733461
TI  - Pharmacokinetics of prophylactic cefazolin in parturients undergoing cesarean
      delivery.
AB  - The objectives of this work were (i) to characterize the pharmacokinetics of
      cefazolin in pregnant women undergoing elective cesarean delivery and in their
      neonates; (ii) to assess cefazolin transplacental transmission; (iii) to evaluate
      the dosing and timing of preoperative, prophylactic administration of cefazolin
      to pregnant women; and (iv) to investigate the impact of maternal dosing on
      therapeutic duration and exposure in newborns. Twenty women received 1 g of
      cefazolin preoperatively. Plasma concentrations of total cefazolin were analyzed
      from maternal blood samples taken before, during, and after delivery; umbilical
      cord blood samples obtained at delivery; and neonatal blood samples collected 24
      h after birth. The distribution volume of cefazolin was 9.44 liters. [corrected]
      The values for pre- and postdelivery clearance were 7.18 and 4.12 liters/h,
      respectively. Computer simulations revealed that the probability of maintaining
      free cefazolin concentrations in plasma above 8 mg/liter during scheduled
      caesarean surgery was <50% in the cord blood when cefazolin was administered in
      doses of <2 g or when it was administered <1 h before delivery. Therapeutic
      concentrations of cefazolin persisted in neonates >5 h after birth. Cefazolin
      clearance increases during pregnancy, and larger doses are recommended for
      surgical prophylaxis in pregnant women to obtain the same antibacterial effect as
      in nonpregnant patients. Cefazolin has a longer half-life in neonates than in
      adults. Maternal administration of up to 2 g of cefazolin is effective and
      produces exposure within clinically approved limits in neonates.

PMID- 24733462
TI  - Randomized, placebo-controlled, single-ascending-dose study of BMS-791325, a
      hepatitis C virus (HCV) NS5B polymerase inhibitor, in HCV genotype 1 infection.
AB  - BMS-791325 is a nonnucleoside inhibitor of hepatitis C virus (HCV) NS5B
      polymerase with low-nanomolar potency against genotypes 1a (50% effective
      concentration [EC50], 3 nM) and 1b (EC50, 7 nM) in vitro. BMS-791325 safety,
      pharmacokinetics, and antiviral activity were evaluated in a double-blind,
      placebo-controlled, single-ascending-dose study in 24 patients (interferon naive
      and experienced) with chronic HCV genotype 1 infection, randomized (5:1) to
      receive a single dose of BMS-791325 (100, 300, 600, or 900 mg) or placebo. The
      prevalence and phenotype of HCV variants at baseline and specific posttreatment
      time points were assessed. Antiviral activity was observed in all cohorts, with a
      mean HCV RNA decline of ~2.5 log10 copies/ml observed 24 h after a single 300-mg
      dose. Mean plasma half-life among cohorts was 7 to 9 h; individual 24-hour levels
      exceeded the protein-adjusted EC90 for genotype 1 at all doses. BMS-791325 was
      generally well tolerated, with no serious adverse events or discontinuations.
      Enrichment for resistance variants was not observed at 100 to 600 mg. At 900 mg,
      variants (P495L/S) associated with BMS-791325 resistance in vitro were
      transiently observed in one patient, concurrent with an observed HCV RNA decline
      of 3.4 log10 IU/ml, but were replaced with wild type by 48 h. Single doses of BMS
      791325 were well tolerated; demonstrated rapid, substantial, and exposure-related
      antiviral activity; displayed dose-related increases in exposure; and showed
      viral kinetic and pharmacokinetic profiles supportive of once- or twice-daily
      dosing. These results support its further development in combination with other
      direct-acting antivirals for HCV genotype 1 infection. (This trial has been
      registered at ClinicalTrials.gov under registration no. NCT00664625.). 

PMID- 24733463
TI  - Phase 1B study of the pharmacokinetics and safety of posaconazole intravenous
      solution in patients at risk for invasive fungal disease.
AB  - This was a phase 1B, dose-ranging, multicenter, pharmacokinetics, and safety
      study of cyclodextrin-based posaconazole intravenous (i.v.) solution administered
      through a central line to subjects at high risk for invasive fungal disease (part
      1 of a 2-part study [phase 1B/3]). Initially, the safety and tolerability of
      single-dose posaconazole i.v. 200 mg (n = 10) were compared with those of a
      placebo (n = 11). Subsequently, 2 doses were evaluated, posaconazole i.v. 200 mg
      once daily (q.d.) (n = 21) and 300 mg q.d. (n = 24). The subjects received twice
      daily (b.i.d.) posaconazole i.v. on day 1, followed by 13 days of posaconazole
      i.v. q.d., then 14 days of posaconazole oral suspension 400 mg b.i.d. The steady
      state (day 14) exposure target (average concentration [areas under concentration
      time curve {AUCs}/24 h, average concentrations at steady state {Cavgs}], of >=
      500 to <= 2,500 ng/ml in >= 90% of the subjects) was achieved by 94% of the
      subjects for 200 mg posaconazole q.d. and by 95% of subjects for 300 mg
      posaconazole q.d. The desired exposure target (mean steady-state Cavg, ~ 1,200
      ng/ml) was 1,180 ng/ml in the 200-mg dosing cohort and was exceeded in the 300-mg
      dosing cohort (1,430 ng/ml). Posaconazole i.v. was well tolerated. Posaconazole
      i.v. 300 mg q.d. was selected for the phase 3 study segment. (This study has been
      registered at ClinicalTrials.gov under registration no. NCT01075984.).

PMID- 24733464
TI  - Prevalence and molecular characteristics of drug-resistant Mycobacterium
      tuberculosis in Hunan, China.
AB  - To determine the prevalence and molecular characteristics of drug-resistant
      tuberculosis in Hunan province, drug susceptibility testing and spoligotyping
      methods were performed among 171 M. tuberculosis isolates. In addition, the
      mutated characteristics of 12 loci, including katG, inhA, rpoB, rpsL, nucleotides
      388 to 1084 of the rrs gene [rrs(388-1084)], embB, pncA, tlyA, eis, nucleotides
      1158 to 1674 of the rrs gene [rrs(1158-1674)], gyrA, and gyrB, among drug
      resistant isolates were also analyzed by DNA sequencing. Our results indicated
      that the prevalences of isoniazid (INH), rifampin (RIF), streptomycin (SM),
      ethambutol (EMB), pyrazinamide (PZA), capreomycin (CAP), kanamycin (KAN),
      amikacin (AKM), and ofloxacin (OFX) resistance in Hunan province were 35.7%,
      26.9%, 20.5%, 9.9% 15.2%, 2.3%, 1.8%, 1.2%, and 10.5%, respectively. The
      previously treated patients presented significantly increased risks for
      developing drug resistance. The majority of M. tuberculosis isolates belonged to
      the Beijing family. Almost all the drug resistance results demonstrated no
      association with genotype. The most frequent mutations of drug-resistant isolates
      were katG codon 315 (katG315), inhA15, rpoB531, rpoB526, rpoB516, rpsL43, rrs514,
      embB306, pncA96, rrs1401, gyrA94, and gyrA90. These results contribute to the
      knowledge of the prevalence of drug resistance in Hunan province and also expand
      the molecular characteristics of drug resistance in China. 

PMID- 24733466
TI  - Quinolone resistance mechanisms in Salmonella enterica serovars Hadar, Kentucky,
      Virchow, Schwarzengrund, and 4,5,12:i:-, isolated from humans in Switzerland, and
      identification of a novel qnrD variant, qnrD2, in S. Hadar.
AB  - Human isolates of Salmonella enterica serovars Hadar, Kentucky, Virchow,
      Schwarzengrund, and the monophasic variant of S. Typhimurium, Salmonella enterica
      subsp. enterica serovar 4,5,12:i:- were examined for mutations within the
      quinolone resistance target genes gyrA, gyrB, parC, and parE and for plasmid
      mediated resistance genes. Differences were observed among the serovars. A novel
      variant of qnrD, qnrD2, was detected in an S. Hadar isolate. 

PMID- 24733465
TI  - Preclinical characterization of BMS-791325, an allosteric inhibitor of hepatitis
      C Virus NS5B polymerase.
AB  - BMS-791325 is an allosteric inhibitor that binds to thumb site 1 of the hepatitis
      C virus (HCV) NS5B RNA-dependent RNA polymerase. BMS-791325 inhibits recombinant
      NS5B proteins from HCV genotypes 1, 3, 4, and 5 at 50% inhibitory concentrations
      (IC50) below 28 nM. In cell culture, BMS-791325 inhibited replication of HCV
      subgenomic replicons representing genotypes 1a and 1b at 50% effective
      concentrations (EC50s) of 3 nM and 6 nM, respectively, with similar (3 to 18 nM)
      values for genotypes 3a, 4a, and 5a. Potency against genotype 6a showed more
      variability (9 to 125 nM), and activity was weaker against genotype 2 (EC50, 87
      to 925 nM). Specificity was demonstrated by the absence of activity (EC50s of >4
      MUM) against a panel of mammalian viruses, and cytotoxic concentrations (50%)
      were >3,000-fold above the HCV EC50. Resistance substitutions selected by BMS
      791325 in genotype 1 replicons mostly mapped to a single site, NS5B amino acid
      495 (P495A/S/L/T). Additive or synergistic activity was observed in combination
      studies using BMS-791325 with alfa interferon plus ribavirin, inhibitors of NS3
      protease or NS5A, and other classes of NS5B inhibitor (palm site 2-binding or
      nucleoside analogs). Plasma and liver exposures in vivo in several animal species
      indicated that BMS-791325 has a hepatotropic disposition (liver-to-plasma ratios
      ranging from 1.6- to 60-fold across species). Twenty-four hours postdose, liver
      exposures across all species tested were >= 10-fold above the inhibitor EC50s
      observed with HCV genotype 1 replicons. These findings support the evaluation of
      BMS-791325 in combination regimens for the treatment of HCV. Phase 3 studies are
      ongoing.

PMID- 24733467
TI  - Positions and numbers of FKS mutations in Candida albicans selectively influence
      in vitro and in vivo susceptibilities to echinocandin treatment.
AB  - Candidemia is the fourth most common kind of microbial bloodstream infection,
      with Candida albicans being the most common causative species. Echinocandins are
      employed as the first-line treatment for invasive candidiasis until the fungal
      species is determined and confirmed by clinical diagnosis. Echinocandins block
      the FKS glucan synthases responsible for embedding beta-(1,3)-d-glucan in the
      cell wall. The increasing use of these drugs has led to the emergence of
      antifungal resistance, and elevated MICs have been associated with single-residue
      substitutions in specific hot spot regions of FKS1 and FKS2. Here, we show for
      the first time the caspofungin-mediated in vivo selection of a double mutation
      within one allele of the FKS1 hot spot 1 in a clinical isolate. We created a set
      of isogenic mutants and used a hematogenous murine model to evaluate the in vivo
      outcomes of echinocandin treatment. Heterozygous and homozygous double mutations
      significantly enhance the in vivo resistance of C. albicans compared with the
      resistance seen with heterozygous single mutations. The various FKS1 hot spot
      mutations differ in the degree of their MIC increase, substance-dependent in vivo
      response, and impact on virulence. Our results demonstrate that echinocandin
      EUCAST breakpoint definitions correlate with the in vivo response when a standard
      dosing regimen is used but cannot predict the in vivo response after a dose
      escalation. Moreover, patients colonized by a C. albicans strain with multiple
      mutations in FKS1 have a higher risk for therapeutic failure. 

PMID- 24733468
TI  - Quantification and validation of ertapenem using a liquid chromatography-tandem
      mass spectrometry method.
AB  - Ertapenem, a carbapenem, relies on time-dependent killing. Therapeutic drug
      monitoring (TDM) should be considered, when ertapenem is used in specific
      populations, to achieve optimal bactericidal activity and optimize drug-dosing
      regimens. No validated liquid chromatography-tandem mass spectrometry (LC-MS/MS)
      method has been reported using deuterated ertapenem as the internal standard. A
      new simple and robust LC-MS/MS method using a quadrupole mass spectrometer was
      developed for analysis of ertapenem in human plasma, using deuterated ertapenem
      as the internal standard. The calibration curve was linear over a range of 0.1
      (lower limit of quantification [LLOQ]) to 125 mg/liter. The calculated accuracy
      ranged from -2.4% to 10.3%. Within-run coefficients of variation (CV) ranged from
      2.7% to 11.8%, and between-run CV ranged from 0% to 8.4%. Freeze-thaw stability
      had a bias of -3.3% and 0.1%. Storage of QC samples for 96 h at 4 degrees C had a
      bias of -4.3 to 5.6%, storage at room temperature for 24 h had a bias of -10.7%
      to -14.8%, and storage in the autosampler had a bias between -2.9% and -10.0%. A
      simple LC-MS/MS method to quantify ertapenem in human plasma using deuterated
      ertapenem as the internal standard has been validated. This method can be used in
      pharmacokinetic studies and in clinical studies by performing TDM. 

PMID- 24733469
TI  - Cefoxitin continuous infusion for lung infection caused by the Mycobacterium
      abscessus group.

PMID- 24733470
TI  - Multiplex PCR for identification of two capsular types in epidemic KPC-producing
      Klebsiella pneumoniae sequence type 258 strains.
AB  - We developed a multiplex PCR assay capable of identifying two capsular
      polysaccharide synthesis sequence types (sequence type 258 [ST258] cps-1 and cps
      2) in epidemic Klebsiella pneumoniae ST258 strains. The assay performed with
      excellent sensitivity (100%) and specificity (100%) for identifying cps types in
      60 ST258 K. pneumoniae sequenced isolates. The screening of 419 ST258 clonal
      isolates revealed a significant association between cps type and K. pneumoniae
      carbapenemase (KPC) variant: cps-1 is largely associated with KPC-2, while cps-2
      is primarily associated with KPC-3. 

PMID- 24733472
TI  - Uptake of polymyxin B into renal cells.
AB  - Polymyxin B is increasingly used as a treatment of last resort against multidrug
      resistant Gram-negative infections. Using a mammalian kidney cell line, we
      demonstrated that polymyxin B uptake into proximal tubular epithelial cells was
      saturable and occurred primarily through the apical membrane, suggesting the
      involvement of transporters in the renal uptake of polymyxin B. Megalin might
      play a role in the uptake and accumulation of polymyxin B into renal cells. 

PMID- 24733471
TI  - Significance and clinical management of persistent low-level viremia and very-low
      level viremia in HIV-1-infected patients.
AB  - A goal of HIV therapy is to sustain suppression of the plasma viral load below
      the detection limits of clinical assays. However, widely followed treatment
      guidelines diverge in their interpretation and recommended management of
      persistent viremia of low magnitude, reflecting the limited evidence base for
      this common clinical finding. Here, we review the incidence, risk factors, and
      potential consequences of low-level HIV viremia (LLV; defined in this review as a
      viremia level of 50 to 500 copies/ml) and very-low-level viremia (VLLV; defined
      as a viremia level of <50 copies/ml detected by clinical assays that have
      quantification cutoffs of <50 copies/ml). Using this framework, we discuss
      practical issues related to the diagnosis and management of patients experiencing
      persistent LLV and VLLV. Compared to viral suppression at <50 or 40 copies/ml,
      persistent LLV is associated with increased risk of antiretroviral drug
      resistance and overt virologic failure. Higher immune activation and HIV
      transmission may be additional undesirable consequences in this population. It is
      uncertain whether LLV of <200 copies/ml confers independent risks, as this level
      of viremia may reflect assay-dependent artifacts or biologically meaningful
      events during suppression. Resistance genotyping should be considered in patients
      with persistent LLV when feasible, and treatment should be modified if resistance
      is detected. There is a dearth of clinical evidence to guide management when
      genotyping is not feasible. Increased availability of genotypic assays for
      samples with viral loads of <400 copies/ml is needed. 

PMID- 24733473
TI  - Efficacy and safety of AVP-21D9, an anthrax monoclonal antibody, in animal models
      and humans.
AB  - Anthrax is an acute infectious disease caused by the spore-forming bacterium
      Bacillus anthracis. Timely administration of antibiotics approved for the
      treatment of anthrax disease may prevent associated morbidity and mortality.
      However, any delay in initiating antimicrobial therapy may result in increased
      mortality, as inhalational anthrax progresses rapidly to the toxemic phase of
      disease. An anthrax antitoxin, AVP-21D9, also known as Thravixa (fully human
      anthrax monoclonal antibody), is being developed as a therapeutic agent against
      anthrax toxemia. The efficacy of AVP-21D9 in B. anthracis-infected New Zealand
      White rabbits and in cynomolgus macaques was evaluated, and its safety and
      pharmacokinetics were assessed in healthy human volunteers. The estimated mean
      elimination half-life values of AVP-21D9 in surviving anthrax-challenged rabbits
      and nonhuman primates (NHPs) ranged from approximately 2 to 4 days and 6 to 11
      days, respectively. In healthy humans, the mean elimination half-life was in the
      range of 20 to 27 days. Dose proportionality was observed for the maximum serum
      concentration (Cmax) of AVP-21D9 and the area under the concentration-time curve
      (AUC). In therapeutic efficacy animal models, treatment with AVP-21D9 resulted in
      survival of up to 92% of the rabbits and up to 67% of the macaques. Single
      infusions of AVP-21D9 were well tolerated in healthy adult volunteers across all
      doses evaluated, and no serious adverse events were reported. (This study has
      been registered at ClinicalTrials.gov under registration no. NCT01202695.). 

PMID- 24733474
TI  - In vitro antifungal susceptibility of Candida glabrata to caspofungin and the
      presence of FKS mutations correlate with treatment response in an
      immunocompromised murine model of invasive infection.
AB  - It has been argued that the in vitro activity of caspofungin (CSP) is not a good
      predictor of the outcome of echinocandin treatment in vivo. We evaluated the in
      vitro activity of CSP and the presence of FKS mutations in the hot spot 1 (HS1)
      region of the FKS1 and FKS2 genes in 17 Candida glabrata strains with a wide
      range of MICs. The efficacy of CSP against systemic infections from each of the
      17 strains was evaluated in a murine model. No HS1 mutations were found in the
      eight strains showing MICs for CSP of <= 0.5 MUg/ml, but they were present in
      eight of the nine strains with MICs of >= 1 MUg/ml, i.e., three in the FKS1 gene
      and five in the FKS2 gene. CSP was effective for treating mice infected with
      strains with MICs of <= 0.5 MUg/ml, showed variable efficacy in animals
      challenged with strains with MICs of 1 MUg/ml, and did not work in those with
      strains with MICs of >1 MUg/ml. In addition, mutations, including one reported
      for the first time, were found outside the HS1 region in the FKS2 gene of six
      strains with different MICs, but their presence did not influence drug efficacy.
      The in vitro activity of CSP was compared with that of another echinocandin,
      anidulafungin, suggesting that the MICs of both drugs, as well as mutations in
      the HS1 regions of the FKS1 and FKS2 genes, are predictive of outcome.

PMID- 24733475
TI  - Pneumocystis jirovecii Rtt109, a novel drug target for Pneumocystis pneumonia in
      immunosuppressed humans.
AB  - Pneumocystis pneumonia (PcP) is a significant cause of morbidity and mortality in
      immunocompromised patients. In humans, PcP is caused by the opportunistic fungal
      species Pneumocystis jirovecii. Progress in Pneumocystis research has been
      hampered by a lack of viable in vitro culture methods, which limits laboratory
      access to human-derived organisms for drug testing. Consequently, most basic drug
      discovery research for P. jirovecii is performed using related surrogate
      organisms such as Pneumocystis carinii, which is derived from immunosuppressed
      rodents. While these studies provide useful insights, important questions arise
      about interspecies variations and the relative utility of identified anti
      Pneumocystis agents against human P. jirovecii. Our recent work has identified
      the histone acetyltransferase (HAT) Rtt109 in P. carinii (i.e., PcRtt109) as a
      potential therapeutic target for PcP, since Rtt109 HATs are widely conserved in
      fungi but are absent in humans. To further address the potential utility of this
      target in human disease, we now demonstrate the presence of a functional Rtt109
      orthologue in the clinically relevant fungal pathogen P. jirovecii (i.e.,
      PjRtt109). In a fashion similar to that of Pcrtt109, Pjrtt109 restores H3K56
      acetylation and genotoxic resistance in rtt109-null yeast. Recombinant PjRtt109
      is an active HAT in vitro, with activity comparable to that of PcRtt109 and yeast
      Rtt109. PjRtt109 HAT activity is also enhanced by the histone chaperone Asf1 in
      vitro. PjRtt109 and PcRtt109 showed similar low micromolar sensitivities to two
      reported small-molecule HAT inhibitors in vitro. Together, these results
      demonstrate that PjRtt109 is a functional Rtt109 HAT, and they support the
      development of anti-Pneumocystis agents directed at Rtt109-catalyzed histone
      acetylation as a novel therapeutic target for human PcP. 

PMID- 24733476
TI  - Selection of drug resistance-mediating Plasmodium falciparum genetic
      polymorphisms by seasonal malaria chemoprevention in Burkina Faso.
AB  - Seasonal malaria chemoprevention (SMC), with regular use of amodiaquine plus
      sulfadoxine-pyrimethamine (AQ/SP) during the transmission season, is now a
      standard malaria control measure in the Sahel subregion of Africa. Another
      strategy under study is SMC with dihydroartemisinin plus piperaquine (DP).
      Plasmodium falciparum single nucleotide polymorphisms (SNPs) in P. falciparum crt
      (pfcrt), pfmdr1, pfdhfr, and pfdhps are associated with decreased response to
      aminoquinoline and antifolate antimalarials and are selected by use of these
      drugs. To characterize selection by SMC of key polymorphisms, we assessed 13 SNPs
      in P. falciparum isolated from children aged 3 to 59 months living in
      southwestern Burkina Faso and randomized to receive monthly DP or AQ/SP for 3
      months in 2009. We compared SNP prevalence before the onset of SMC and 1 month
      after the third treatment in P. falciparum PCR-positive samples from 120 randomly
      selected children from each treatment arm and an additional 120 randomly selected
      children from a control group that did not receive SMC. The prevalence of
      relevant mutations was increased after SMC with AQ/SP. Significant selection was
      seen for pfcrt 76T (68.5% to 83.0%, P = 0.04), pfdhfr 59R (54.8% to 83.3%, P =
      0.0002), and pfdhfr 108N (55.0% to 87.2%, P = 0.0001), with trends toward
      selection of pfmdr1 86Y, pfdhfr 51I, and pfdhps 437G. After SMC with DP, only
      borderline selection of wild-type pfmdr1 D1246 (mutant; 7.7% to 0%, P = 0.05) was
      seen. In contrast to AQ/SP, SMC with DP did not clearly select for known
      resistance-mediating polymorphisms. SMC with AQ/SP, but not DP, may hasten the
      development of resistance to components of this regimen. (This study has been
      registered at ClinicalTrials.gov under registration no. NCT00941785.). 

PMID- 24733479
TI  - The changing legal climate for physician aid in dying.

PMID- 24733477
TI  - Lysine acetylation in sexual stage malaria parasites is a target for antimalarial
      small molecules.
AB  - Therapies to prevent transmission of malaria parasites to the mosquito vector are
      a vital part of the global malaria elimination agenda. Primaquine is currently
      the only drug with such activity; however, its use is limited by side effects.
      The development of transmission-blocking strategies requires an understanding of
      sexual stage malaria parasite (gametocyte) biology and the identification of new
      drug leads. Lysine acetylation is an important posttranslational modification
      involved in regulating eukaryotic gene expression and other essential processes.
      Interfering with this process with histone deacetylase (HDAC) inhibitors is a
      validated strategy for cancer and other diseases, including asexual stage malaria
      parasites. Here we confirm the expression of at least one HDAC protein in
      Plasmodium falciparum gametocytes and show that histone and nonhistone protein
      acetylation occurs in this life cycle stage. The activity of the canonical HDAC
      inhibitors trichostatin A (TSA) and suberoylanilide hydroxamic acid (SAHA;
      Vorinostat) and a panel of novel HDAC inhibitors on early/late-stage gametocytes
      and on gamete formation was examined. Several compounds displayed early/late
      stage gametocytocidal activity, with TSA being the most potent (50% inhibitory
      concentration, 70 to 90 nM). In contrast, no inhibitory activity was observed in
      P. falciparum gametocyte exflagellation experiments. Gametocytocidal HDAC
      inhibitors caused hyperacetylation of gametocyte histones, consistent with a mode
      of action targeting HDAC activity. Our data identify HDAC inhibitors as being
      among a limited number of compounds that target both asexual and sexual stage
      malaria parasites, making them a potential new starting point for gametocytocidal
      drug leads and valuable tools for dissecting gametocyte biology. 

PMID- 24733478
TI  - Efficiency of incorporation and chain termination determines the inhibition
      potency of 2'-modified nucleotide analogs against hepatitis C virus polymerase.
AB  - Ribonucleotide analog inhibitors of the RNA-dependent RNA polymerase of hepatitis
      C virus (HCV) represent one of the most exciting recent developments in HCV
      antiviral therapy. Although it is well established that these molecules cause
      chain termination by competing at the triphosphate level with natural nucleotides
      for incorporation into elongating RNA, strategies to rationally optimize
      antiviral potency based on enzyme kinetics remain elusive. In this study, we used
      the isolated HCV polymerase elongation complex to determine the pre-steady-state
      kinetics of incorporation of 2'F-2'C-Me-UTP, the active metabolite of the anti
      HCV drug sofosbuvir. 2'F-2'C-Me-UTP was efficiently incorporated by HCV
      polymerase with apparent Kd (equilibrium constant) and kpol (rate of nucleotide
      incorporation at saturating nucleotide concentration) values of 113 +/- 28 MUM
      and 0.67 +/- 0.05 s(-1), respectively, giving an overall substrate efficiency
      (kpol/Kd) of 0.0059 +/- 0.0015 MUM(-1) s(-1). We also measured the substrate
      efficiency of other UTP analogs and found that substitutions at the 2' position
      on the ribose can greatly affect their level of incorporation, with a rank order
      of OH > F > NH2 > F-C-Me > C-Me > N3 > ara. However, the efficiency of chain
      termination following the incorporation of UMP analogs followed a different
      order, with only 2'F-2'C-Me-, 2'C-Me-, and 2'ara-UTP causing complete and
      immediate chain termination. The chain termination profile of the 2'-modified
      nucleotides explains the apparent lack of correlation observed across all
      molecules between substrate efficiency at the single-nucleotide level and their
      overall inhibition potency. To our knowledge, these results provide the first
      attempt to use pre-steady-state kinetics to uncover the mechanism of action of 2'
      modified NTP analogs against HCV polymerase. 

PMID- 24733480
TI  - Development and validation of the AFSympTM: an atrial fibrillation-specific
      measure of patient-reported symptoms.
AB  - BACKGROUND: Patients with atrial fibrillation (AF) can be severely incapacitated
      by symptoms, but validated symptom measures are lacking. The aim of this study
      was to develop an AF-specific symptom questionnaire (AFSympTM). METHODS:
      Following a literature review, qualitative interviews with 91 patients (United
      States [US], n = 30; United Kingdom [UK], n = 16; France, n = 15; Germany, n =
      15; Japan, n = 15) with paroxysmal, persistent, and permanent AF were conducted
      to identify emergent concepts and to develop the items and response options for
      the AFSympTM. Clinical experts (n = 21) in the US, the UK, France, Germany, and
      Japan provided feedback on the most clinically relevant symptoms via an email
      survey. Cognitive interviews with 30 patients were conducted to evaluate content
      validity. A prospective, observational, psychometric evaluation study (n = 313)
      consisting of two study visits was performed at 32 sites across the US. RESULTS:
      After item reduction, the AFSympTM consisted of 11 items with a 1-week recall
      period. Exploratory and confirmatory factor analysis resulted in three subscales
      (heart symptoms, tiredness, chest discomfort) and two items: dizziness and
      shortness of breath. Internal consistency was strong across subscales (Cronbach's
      alpha 0.82-0.91). The test-retest reliability of items and subscales was
      acceptable (intra-class correlation [ICC] 0.58-0.78). The reproducibility of the
      single global score was strong (ICC 0.78). The construct and known-groups
      validity was acceptable. CONCLUSION: The AFSympTM demonstrates evidence of
      reliability and validity as a comprehensive measure of AF symptoms that can be
      used to assess patient outcomes in clinical and research settings. More research
      is needed to evaluate the instrument's responsiveness.

PMID- 24733482
TI  - [Not Available].

PMID- 24733481
TI  - Neurotic disorders of general medical outpatients in Xi'an, China: knowledge,
      attitudes, and help-seeking preferences.
AB  - OBJECTIVE: This study assessed knowledge of neurotic disorders, and attitudes and
      preferences toward professional help and treatment for them, among general
      medical outpatients in general hospitals in Xi'an, China. METHODS: General
      medical outpatients (N=372) from general hospitals in China were recruited by
      using a stratified cluster sampling method between June and September 2010. In
      face-to-face interviews, participants age 16 years or older were assessed for
      their knowledge, attitudes, and help-seeking preferences in regard to neurotic
      disorders (obsessive-compulsive disorder, social phobia, and panic disorder).
      Demographic data were also collected. RESULTS: Lack of insight into neurotic
      disorders was common among medical outpatients in general hospitals of Xi'an,
      China. Twenty-four percent to 58% of the outpatients had some knowledge of the
      symptoms and treatment of neurotic disorders. Only 11% of the outpatients would
      reveal to others that they or a family member suffered from neurotic disorders.
      When faced with the problem of neurotic disorders, the preference of the
      respondents was to visit a psychiatrist in a general hospital (44%), and only 17%
      would visit a physician in a psychiatric hospital. Major ways for the outpatients
      to obtain knowledge regarding neurotic disorders were via radio and television
      (36%), and only 18%-23% of outpatients obtained knowledge about neurotic
      disorders through printed public health materials and by attending lectures.
      CONCLUSIONS: Study results underscore the need for information campaigns aimed at
      improving the mental health literacy of general medical outpatients. Such
      campaigns must consider culturally relevant beliefs to facilitate the development
      of specific educational programs.

PMID- 24733483
TI  - Self-perception of when old age begins for Cambodian elders living in the United
      States.
AB  - OBJECTIVE: To deepen the understanding of the life course of refugees this study
      explores the question: when do Cambodian elders perceive the beginning of old
      age? METHODS: In-depth interviews were conducted with 32 Cambodians, age range 53
      82, who attended an elder day center in an urban setting in Massachusetts.
      Interviews were transcribed and analyzed using the modified grounded theory
      approach. RESULTS: The analysis revealed that the participants primarily reported
      two determinants to defining when old age begins: 1) the body "has too many
      illnesses" due to harsh working conditions; and 2) social role transition into
      grandparent. DISCUSSION: This study extends research on cultural differences in
      aging, specifically identifying the cultural difference in the definition of when
      "old age" begins. Age is culturally derived and creates expectations for social
      roles, health, self-identity, and behavior. Understanding how refugees experience
      the cultural discrepancies in their expectations of aging can inform providers
      who serve this population.

PMID- 24733485
TI  - New specimens of Yanornis indicate a piscivorous diet and modern alimentary
      canal.
AB  - A crop adapted for an herbivorous diet of seeds has previously been documented in
      the Early Cretaceous birds Sapeornis and Hongshanornis. Here we report on several
      specimens of Yanornis that preserve a crop containing fish. One specimen
      preserves two whole fish in the oesophagus, indicating that Early Cretaceous
      birds shared trophic specializations with Neornithes for the increased energetic
      demands of flight--namely the storing of food for later consumption when the
      stomach is full. Whole fish also indicate that despite their presence, teeth were
      not used to orally process food, suggesting the hypertrophied dentition in this
      taxon were utilized in prey capture. The presence of macerated fish bones in the
      crop of other specimens indicates the highly efficient advanced muscular system
      of peristalsis responsible for moving ingested items between different segments
      of the alimentary canal was also in place. Despite the fact many features of the
      modern avian alimentary canal are inferred to compensate for the absence of teeth
      in birds (expandable oesophagus, grinding gizzard), the derived alimentary canal
      was apparently present in toothed Cretaceous birds. Although Yanornis was
      considered to have switched their diet from piscivorous to herbivorous, based on
      position and morphology we reinterpret the gastroliths reported in one specimen
      as sand impacted in the intestines, and reconstruct the taxon as primarily
      piscivorous. This is a novel interpretation for fossilized gastroliths, and the
      first documentation of this condition in the fossil record.

PMID- 24733486
TI  - Enhancement of CYP3A4 activity in Hep G2 cells by lentiviral transfection of
      hepatocyte nuclear factor-1 alpha.
AB  - Human hepatoma cell lines are commonly used as alternatives to primary
      hepatocytes for the study of drug metabolism in vitro. However, the phase I
      cytochrome P450 (CYP) enzyme activities in these cell lines occur at a much lower
      level than their corresponding activities in primary hepatocytes, and thus these
      cell lines may not accurately predict drug metabolism. In the present study, we
      selected hepatocyte nuclear factor-1 alpha (HNF1alpha) from six transcriptional
      regulators for lentiviral transfection into Hep G2 cells to optimally increase
      their expression of the CYP3A4 enzyme, which is the major CYP enzyme in the human
      body. We subsequently found that HNF1alpha-transfected Hep G2 enhanced the CYP3A4
      expression in a time- and dose-dependent manner and the activity was noted to
      increase with time and peaked 7 days. With a multiplicity of infection (MOI) of
      100, CYP3A4 expression increased 19-fold and enzyme activity more than doubled at
      day 7. With higher MOI (1,000 to 3,000), the activity increased 8- to 10-fold;
      however, it was noted the higher MOI, the higher cell death rate and lower cell
      survival. Furthermore, the CYP3A4 activity in the HNF1alpha-transfected cells
      could be induced by CYP3A4-specific inducer, rifampicin, and metabolized
      nifedipine in a dose-dependent manner. With an MOI of 3,000, nifedipine
      metabolizing activity was 6-fold of control and as high as 66% of primary
      hepatocytes. In conclusion, forceful delivery of selected transcriptional
      regulators into human hepatoma cells might be a valuable method to enhance the
      CYP activity for a more accurate determination of drug metabolism in vitro. 

PMID- 24733487
TI  - A phosphoramidite-based [FeFe]H2ase functional mimic displaying fast
      electrocatalytic proton reduction.
AB  - A phosphoramidite modified [FeFe]H2ase mimic is studied as a model for
      photodriven production of H2. On cathodic activation, the pyridyl-phosphoramidite
      complex exhibits a strongly enhanced rate of proton reduction over the previously
      reported pyridylphosphine model at the same overpotential. Analysis of the cyclic
      voltammograms shows an apparent H2 evolution rate strongly influenced by the
      presence of both side-bound pyridyl and phosphorous-bound dimethylamino moieties
      at the phosphoramidite ligands. This difference is ascribed to the basic amines
      acting as proton relays. 

PMID- 24733490
TI  - Mechanically adaptive organic transistors for implantable electronics.
AB  - A unique form of adaptive electronics is demonstrated, which change their
      mechanical properties from rigid and planar to soft and compliant, in order to
      enable soft and conformal wrapping around 3D objects, including biological
      tissue. These devices feature excellent mechanical robustness and maintain
      initial electrical properties even after changing shape and stiffness. 

PMID- 24733492
TI  - 13C NMR relaxation and reorientation dynamics in imidazolium-based ionic liquids:
      revising interpretation.
AB  - The temperature dependencies of (13)C NMR relaxation rates in [bmim]PF6 ionic
      liquid have been measured and the characteristic times (tauc) for the cation
      reorientation have been recalculated. We found the origin of the incorrect tauc
      temperature dependencies that were earlier reported for ring carbons in a number
      of imidazolium-based ILs. After a correction of the approach (13)C T1, the
      relaxation data allowed us to obtain the characteristic times for an orientation
      mobility of each carbon, and a complicated experiment, such as NOE, was not
      required. Thus the applicability of (13)C NMR relaxation rate measurements to the
      calculation of the characteristic times for reorientation of all the carbons of
      the [bmim](+) cation was confirmed and our findings have shown that a (13)C NMR
      relaxation technique allowed its application to ionic liquids to be equally
      successful as for other liquid systems. 

PMID- 24733489
TI  - New insights into Dehalococcoides mccartyi metabolism from a reconstructed
      metabolic network-based systems-level analysis of D. mccartyi transcriptomes.
AB  - Organohalide respiration, mediated by Dehalococcoides mccartyi, is a useful
      bioremediation process that transforms ground water pollutants and known human
      carcinogens such as trichloroethene and vinyl chloride into benign ethenes.
      Successful application of this process depends on the fundamental understanding
      of the respiration and metabolism of D. mccartyi. Reductive dehalogenases,
      encoded by rdhA genes of these anaerobic bacteria, exclusively catalyze
      organohalide respiration and drive metabolism. To better elucidate D. mccartyi
      metabolism and physiology, we analyzed available transcriptomic data for a pure
      isolate (Dehalococcoides mccartyi strain 195) and a mixed microbial consortium
      (KB-1) using the previously developed pan-genome-scale reconstructed metabolic
      network of D. mccartyi. The transcriptomic data, together with available
      proteomic data helped confirm transcription and expression of the majority genes
      in D. mccartyi genomes. A composite genome of two highly similar D. mccartyi
      strains (KB-1 Dhc) from the KB-1 metagenome sequence was constructed, and operon
      prediction was conducted for this composite genome and other single genomes. This
      operon analysis, together with the quality threshold clustering analysis of
      transcriptomic data helped generate experimentally testable hypotheses regarding
      the function of a number of hypothetical proteins and the poorly understood
      mechanism of energy conservation in D. mccartyi. We also identified functionally
      enriched important clusters (13 for strain 195 and 11 for KB-1 Dhc) of co
      expressed metabolic genes using information from the reconstructed metabolic
      network. This analysis highlighted some metabolic genes and processes, including
      lipid metabolism, energy metabolism, and transport that potentially play
      important roles in organohalide respiration. Overall, this study shows the
      importance of an organism's metabolic reconstruction in analyzing various "omics"
      data to obtain improved understanding of the metabolism and physiology of the
      organism. 

PMID- 24733493
TI  - Experts voice concerns over safety of prostate cancer monitoring.

PMID- 24733495
TI  - Psychometric characteristics of the Night Eating Questionnaire in a Middle East
      population.
AB  - OBJECTIVE: To translate and validate the Night Eating Questionnaire (NEQ) into
      Arabic and to describe the distribution of night eating in an Egyptian sample.
      METHOD: The NEQ was translated into Arabic and administered to 420 university
      students in Cairo, Egypt. Reliability, validity, and clinical cut-scores were
      generated for the Arabic NEQ. Distribution and demographic information were
      examined. RESULTS: Cronbach's alpha for the Arabic NEQ was 0.54. A first order
      confirmatory factor analysis yielded five factors: 1: Nocturnal Ingestions,
      Factor 2: Evening Hyperphagia, Factor 3: Morning Anorexia, Factor 4: Insomnia,
      and Factor 5: Mood. A total NEQ score of 26 was determined to be very high after
      T-score transformation. Of the students, 4.8% scored above this cut score, and no
      differences for total NEQ score were found for demographic variables. DISCUSSION:
      The Arabic NEQ generated a lower internal consistency score as compared to
      previous translations, but a similar factor structure. A cut score of 26 is
      similar to that determined significant for screening purposes in the original
      English version, and the proportion of those scoring above it is also similar to
      those of several international community samples. More research is needed to
      characterize night eating syndrome, its symptoms, and clinical impact in the
      Arabic culture.

PMID- 24733494
TI  - Rapid regulation of nuclear proteins by rapamycin-induced translocation in
      fission yeast.
AB  - Genetic analysis of protein function requires a rapid means of inactivating the
      gene under study. Typically, this exploits temperature-sensitive mutations or
      promoter shut-off techniques. We report the adaptation to Schizosaccharomyces
      pombe of the anchor-away technique, originally designed in budding yeast by
      Laemmli lab. This method relies on a rapamycin-mediated interaction between the
      FRB- and FKBP12-binding domains to relocalize nuclear proteins of interest to the
      cytoplasm. We demonstrate a rapid nuclear depletion of abundant proteins as proof
      of principle.

PMID- 24733497
TI  - Successful en bloc endoscopic submucosal dissection of early gastric cancer and
      rectal lateral spreading tumor in a Greek hospital.

PMID- 24733500
TI  - The value of time in assessing the effectiveness of newborn screening for
      congenital adrenal hyperplasia.

PMID- 24733499
TI  - Tissue-specific fatty acids response to different diets in common carp (Cyprinus
      carpio L.).
AB  - Fish depend on dietary fatty acids (FA) to support their physiological condition
      and health. Exploring the FA distribution in common carp (Cyprinus carpio), one
      of the world's most consumed freshwater fish, is important to understand how and
      where FA of different sources are allocated. We investigated diet effects on the
      composition of polar and neutral lipid fatty acids (PLFA and NLFA, respectively)
      in eight different tissues (dorsal and ventral muscle, heart, kidney, intestine,
      eyes, liver and adipose tissue) of common carp. Two-year old carp were exposed to
      three diet sources (i.e., zooplankton, zooplankton plus supplementary feeds
      containing vegetable, VO, or fish oil, FO) with different FA composition. The
      PLFA and NLFA response was clearly tissue-specific after 210 days of feeding on
      different diets. PLFA were generally rich in omega-3 polyunsaturated FA and only
      marginally influenced by dietary FA, whereas the NLFA composition strongly
      reflected dietary FA profiles. However, the NLFA composition in carp tissues
      varied considerably at low NLFA mass ratios, suggesting that carp is able to
      regulate the NLFA composition and thus FA quality in its tissues when NLFA
      contents are low. Finally, this study shows that FO were 3X more retained than VO
      as NLFA particularly in muscle tissues, indicating that higher nutritional
      quality feeds are selectively allocated into tissues and thus available for human
      consumption. 

PMID- 24733501
TI  - Synthesis and f-element ligation properties of NCMPO-decorated pyridine N-oxide
      platforms.
AB  - Stepwise syntheses of 2-{[2-(diphenylphosphoryl)acetamido]methyl}pyridine 1
      oxide, 2-[Ph2P(O)CH2C(O)N(H)CH2]C5H4NO (6), 2-{[2
      (diphenylphosphoryl)acetamido]methyl}-6-[(diphenylphosphoryl)methyl]pyridine 1
      oxide, 2-[Ph2P(O)CH2C(O)N(H)CH2]-6-[Ph2P(O)CH2]C5H3NO (7) and 2,6-bis{[2
      (diphenylphosphoryl)acetamido]methyl}pyridine 1-oxide, 2,6
      [Ph2P(O)CH2C(O)N(H)CH2]2C5H3NO (8), are reported along with spectroscopic
      characterization data and single crystal X-ray diffraction structure
      determination for 6.2H2O, 7 and 2,6-[Ph2P(O)CH2C(O)N(H)CH2]2C5H3N.MeOH 18.MeOH,
      the pyridine precursor of 8. Molecular mechanics computations indicate that 6, 7
      and 8 should experience minimal steric hindrance to donor group reorganization
      that would permit tridentate, tetradentate and pentadentate docking structures
      for the respective ligands on lanthanide cations. However, crystal structure
      determination for the lanthanide complexes, {[Yb(6)(NO3)3].(MeOH)}n,
      {[Lu(6)(NO3)3].(MeOH)}n, [Er(6)2(H2O)2](NO3)3.(H2O)4}n,
      {[La(13)(NO3)3(MeOH)].(MeOH)}n, {[Eu(7)(NO3)2(EtOAc)0.5(H2O)0.5](NO3)}2.MeOH and
      [Dy3(7)4(NO3)4(H2O)2](NO3)5.(MeOH)5.(H2O)2 reveal solid-state structures with
      mixed chelating/bridging ligand : Ln(III) interactions that employ lower than the
      maximal denticity. The binding of 6 and 7 with Eu(III) in the solid state and in
      MeOH solutions is also accessed by emission spectroscopy. The acid dependence for
      solvent extractions with 6 and 7 in 1,2-dichloroethane for Eu(III) and Am(III) in
      nitric acid solutions is described and compared with the behavior of n
      octyl(phenyl)-N,N-diisobutylcarbamoylmethylphosphine oxide (OPhDiBCMPO, 1b) and 2
      [(diphenyl)phosphinoylmethyl]pyridine N-oxide (DPhNOPO, 4a).

PMID- 24733504
TI  - Prevalence of mental health problems among Iraq and Afghanistan veterans who have
      and have not received VA services.
AB  - OBJECTIVE: Roughly half of veterans who served in Operation Enduring Freedom and
      Operation Iraqi Freedom (OEF/OIF) have not received services from the Veterans
      Health Administration (VHA). This study assessed probable posttraumatic stress
      disorder (PTSD) and depression among OEF/OIF veterans by receipt of VHA services.
      METHODS: In 2010 a mixed-mode survey assessing symptoms and VHA services
      utilization was fielded in a random sample of 913 New York State OEF/OIF
      veterans. RESULTS: Probable PTSD and depression were roughly three times more
      common among veterans who had received VHA services (N=537) (PTSD, 23%;
      depression, 21%) than those who had not (N=376) (PTSD, 6%; depression, 8%).
      CONCLUSIONS: Studies of veterans receiving VHA services likely overstate the
      prevalence of mental health problems among the broader OEF/OIF veteran
      population. However, many veterans with mental health problems are not receiving
      VHA services. Policies that improve outreach to this population may improve
      health outcomes.

PMID- 24733505
TI  - Carbon nanotube and graphene hybrid thin film for transparent electrodes and
      field effect transistors.

PMID- 24733503
TI  - MuRF1 activity is present in cardiac mitochondria and regulates reactive oxygen
      species production in vivo.
AB  - MuRF1 is a previously reported ubiquitin-ligase found in striated muscle that
      targets troponin I and myosin heavy chain for degradation. While MuRF1 has been
      reported to interact with mitochondrial substrates in yeast two-hybrid studies,
      no studies have identified MuRF1's role in regulating mitochondrial function to
      date. In the present study, we measured cardiac mitochondrial function from
      isolated permeabilized muscle fibers in previously phenotyped MuRF1 transgenic
      and MuRF1-/- mouse models to determine the role of MuRF1 in intermediate energy
      metabolism and ROS production. We identified a significant decrease in reactive
      oxygen species production in cardiac muscle fibers from MuRF1 transgenic mice
      with increased alpha-MHC driven MuRF1 expression. Increased MuRF1 expression in
      ex vivo and in vitro experiments revealed no alterations in the respiratory chain
      complex I and II function. Working perfusion experiments on MuRF1 transgenic
      hearts demonstrated significant changes in glucose oxidation. However, total
      oxygen consumption was decreased [corrected]. This data provides evidence for
      MuRF1 as a novel regulator of cardiac ROS, offering another mechanism by which
      increased MuRF1 expression may be cardioprotective in ischemia reperfusion
      injury, in addition to its inhibition of apoptosis via proteasome-mediate
      degradation of c-Jun. The lack of mitochondrial function phenotype identified in
      MuRF1-/- hearts may be due to the overlapping interactions of MuRF1 and MuRF2
      with energy regulating proteins found by yeast two-hybrid studies reported here,
      implying a duplicity in MuRF1 and MuRF2's regulation of mitochondrial function.

PMID- 24733506
TI  - Wrist fracture in a 6-year-old girl after an accidental electric shock at low
      voltages.
AB  - Bone injuries related to electric shocks are usually seen with high-voltage
      current exposure or with additional traumas, such as falls. Few cases of
      fractures after electric shocks at low-voltages (with no direct blunt trauma) are
      reported in the literature. They result from electrically-induced tetanic muscle
      contractions. Most of them involve the proximal appendicular skeleton, while
      distal fractures of limbs are uncommon. We report the case of a 6-year-old girl
      who suffered local superficial burns of the hand and a distal radius buckle-type
      fracture after sustaining a 230-V electric shock. The accident occurred while the
      girl was touching with the right hand the metallic stand of a non-insulated
      street lamp. She felt a sudden jolt and managed to pull her hand free quickly,
      without falling or losing consciousness. The superficial burns of the hand were
      consistent with Jellinek's electric marks, while the buckle fracture of the
      radius was consistent with a forceful contraction of the flexor muscles of the
      hand. Only four cases of radius fractures resulting from accidental electric
      shocks at low voltages have been previously reported in the literature. All of
      them involved pediatric patients, suggesting that a child's vulnerability to this
      kind of fracture may exist. The present case is the youngest one ever described. 

PMID- 24733507
TI  - Functional consequences of the over-expression of TRPC6 channels in HEK cells:
      impact on the homeostasis of zinc.
AB  - The canonical transient receptor potential 6 (TRPC6) protein is a non-selective
      cation channel able to transport essential trace elements like iron (Fe) and zinc
      (Zn) through the plasma membrane. Its over-expression in HEK-293 cells causes an
      intracellular accumulation of Zn, indicating that it could be involved in Zn
      transport. This finding prompted us to better understand the role played by TRPC6
      in Zn homeostasis. Experiments done using the fluorescent probe FluoZin-3 showed
      that HEK cells possess an intracellular pool of mobilisable Zn present in
      compartments sensitive to the vesicular proton pump inhibitor Baf-A, which
      affects endo/lysosomes. TRPC6 over-expression facilitates the basal uptake of Zn
      and enhances the size of the pool of Zn sensitive to Baf-A. Quantitative RT-PCR
      experiments showed that TRPC6 over-expression does not affect the mRNA expression
      of Zn transporters (ZnT-1, ZnT-5, ZnT-6, ZnT-7, ZnT-9, Zip1, Zip6, Zip7, and
      Zip14); however it up-regulates the mRNA expression of metallothionein-I and -II.
      This alters the Zn buffering capacities of the cells as illustrated by the
      experiments done using the Zn ionophore Na pyrithione. In addition, HEK cells
      over-expressing TRPC6 grow slower than their parental HEK cells. This feature can
      be mimicked by growing HEK cells in a culture medium supplemented with 5 MUM of
      Zn acetate. Finally, a proteomic analysis revealed that TRPC6 up-regulates the
      expression of the actin-associated proteins ezrin and cofilin-1, and changes the
      organisation of the actin cytoskeleton without changing the cellular actin
      content. Altogether, these data indicate that TRPC6 is participating in the
      transport of Zn and influences the Zn storage and buffering capacities of the
      cells. 

PMID- 24733509
TI  - Roles of water molecules in trapping carbon dioxide molecules inside the
      interlayer space of graphene oxides.
AB  - Density functional theory (DFT) calculations were employed to investigate the
      energetics of carbon dioxide migration within hydrated or anhydrous graphene
      oxides (GOs). When anhydrous GO structures contain a carbon dioxide molecule, the
      carbon dioxide interacts repulsively with the GO layers to increase the
      interlayer spacing. The repulsive electrostatic interactions are reduced by the
      insertion of water molecules into CO2-containing GO structures due to the
      occurrence of attractive water-layer interactions through hydrogen bonding.
      Consequently, the interlayer spacings in CO2-containing hydrated structures are
      shortened compared with those in the anhydrous structures. The results indicate
      that the intercalated water molecules have the ability to connect the GO layers
      in the presence of carbon dioxide. Furthermore, the DFT calculations indicated
      that the GO interlayer spacings, which are influenced by the intercalation of
      water molecules, control carbon dioxide migration within the GO layers. The
      importance of the interlayer spacings on the migration of carbon dioxide arises
      from the occurrence of repulsive interactions between CO2 and oxygen-containing
      groups attached on the graphene sheets. When the GO interlayer spacings are short
      due to the presence of intercalated water molecules, the repulsive interactions
      between carbon dioxide and the GO layers are strong enough to prevent CO2 from
      migrating from its original position. Such repulsive interactions do not occur
      during the migration of CO2 within anhydrous GO structures because of the
      relatively longer interlayer spacing. Accordingly, CO2 migrates within anhydrous
      GO with a less significant barrier, indicating that carbon dioxide molecules are
      easily released from the GO. 

PMID- 24733508
TI  - History of pregnancy loss increases the risk of mental health problems in
      subsequent pregnancies but not in the postpartum.
AB  - While grief, emotional distress and other mental health conditions have been
      associated with pregnancy loss, less is known about the mental health impact of
      these events during subsequent pregnancies and births. This paper examined the
      impact of any type of pregnancy loss on mental health in a subsequent pregnancy
      and postpartum. Data were obtained from a sub-sample (N = 584) of the 1973-78
      cohort of the Australian Longitudinal Study on Women's Health, a prospective
      cohort study that has been collecting data since 1996. Pregnancy loss was defined
      as miscarriage, termination due to medical reasons, ectopic pregnancy and
      stillbirth. Mental health outcomes included depression, anxiety, stress or
      distress, sadness or low mood, excessive worry, lack of enjoyment, and feelings
      of guilt. Demographic factors and mental health history were controlled for in
      the analysis. Women with a previous pregnancy loss were more likely to experience
      sadness or low mood (AOR = 1.75, 95% CI: 1.11 to 2.76, p = 0.0162), and excessive
      worry (AOR = 2.01, 95% CI: 1.24 to 3.24, p = 0.0043) during a subsequent
      pregnancy, but not during the postpartum phase following a subsequent birth.
      These results indicate that while women who have experienced a pregnancy loss are
      a more vulnerable population during a subsequent pregnancy, these deficits are
      not evident in the postpartum. 

PMID- 24733510
TI  - Adjusting for misclassification in a stratified biomarker clinical trial.
AB  - Clinical trials utilizing predictive biomarkers have become a research focus in
      personalized medicine. We investigate the effects of biomarker misclassification
      on the design and analysis of stratified biomarker clinical trials. For a variety
      of inference problems including marker-treatment interaction in particular, we
      show that marker misclassification may have profound adverse effects on the
      coverage of confidence intervals, power of the tests, and required sample sizes.
      For each inferential problem, we propose methods to adjust for the classification
      errors.

PMID- 24733511
TI  - Lactobacillus amylovorus inhibits the TLR4 inflammatory signaling triggered by
      enterotoxigenic Escherichia coli via modulation of the negative regulators and
      involvement of TLR2 in intestinal Caco-2 cells and pig explants.
AB  - Inflammation derived from pathogen infection involves the activation of toll-like
      receptor (TLR) signaling. Despite the established immunomodulatory activities of
      probiotics, studies relating the ability of such bacteria to inhibit the TLR
      signaling pathways are limited or controversial. In a previous study we showed
      that Lactobacillus amylovorus DSM 16698T, a novel lactobacillus isolated from
      unweaned pigs, protects the intestinal cells from enterotoxigenic Escherichia
      coli (ETEC) K88 infection through cytokine regulation. In the present study we
      investigated whether the ability of L. amylovorus to counteract the inflammatory
      status triggered by ETEC in intestine is elicited through inhibition of the TLR4
      signaling pathway. We used the human intestinal Caco-2/TC7 cells and intestinal
      explants isolated from 5 week-old crossbreed Pietrain/Duroc/Large-White piglets,
      treated with ETEC, L. amylovorus or L. amylovorus cell free supernatant, either
      alone or simultaneously with ETEC. Western blot analysis showed that L.
      amylovorus and its cell free supernatant suppress the activation of the different
      steps of TLR4 signaling in Caco-2/TC7 cells and pig explants, by inhibiting the
      ETEC induced increase in the level of TLR4 and MyD88, the phosphorylation of the
      IKKalpha, IKKbeta, IkappaBalpha and NF-kappaB subunit p65, as well as the over
      production of inflammatory cytokines IL-8 and IL-1beta. The immunofluorescence
      analysis confirms the lack of phospho-p65 translocation into the nucleus. These
      anti-inflammatory effects are achieved through modulation of the negative
      regulators Tollip and IRAK-M. We also found that L. amylovorus blocks the up
      regulation of the extracellular heat shock protein (Hsp)72 and Hsp90, that are
      critical for TLR4 function. By using anti-TLR2 antibody, we demonstrate that TLR2
      is required for the suppression of TLR4 signaling activation. These results may
      contribute to develop therapeutic interventions using L. amylovorus in intestinal
      disorders of piglets and humans. 

PMID- 24733512
TI  - Plasma lipidomic profiling of treated HIV-positive individuals and the
      implications for cardiovascular risk prediction.
AB  - BACKGROUND: The increased risk of coronary artery disease in human
      immunodeficiency virus (HIV) positive patients is collectively contributed to by
      the human immunodeficiency virus and antiretroviral-associated dyslipidaemia. In
      this study, we investigate the characterisation of the plasma lipid profiles of
      treated HIV patients and the relationship of 316 plasma lipid species across
      multiple lipid classes with the risk of future cardiovascular events in HIV
      positive patients. METHODS: In a retrospective case-control study, we analysed
      plasma lipid profiles of 113 subjects. Cases (n = 23) were HIV-positive
      individuals with a stored blood sample available 12 months prior to their
      diagnosis of coronary artery disease (CAD). They were age and sex matched to HIV
      positive individuals without a diagnosis of CAD (n = 45) and with healthy HIV
      negative volunteers (n = 45). RESULTS: Association of plasma lipid species and
      classes with HIV infection and cardiovascular risk in HIV were determined. In
      multiple logistic regression, we identified 83 lipids species and 7 lipid classes
      significantly associated with HIV infection and a further identified 74 lipid
      species and 8 lipid classes significantly associated with future cardiovascular
      events in HIV-positive subjects. Risk prediction models incorporating lipid
      species attained an area under the receiver operator characteristic curve (AUC)
      of 0.78 (0.775, 0.785)) and outperformed all other tested markers and risk scores
      in the identification of HIV-positive subjects with increased risk of
      cardiovascular events. CONCLUSIONS: Our results demonstrate that HIV-positive
      patients have significant differences in their plasma lipid profiles compared
      with healthy HIV-negative controls and that numerous lipid species were
      significantly associated with elevated cardiovascular risk. This suggests a
      potential novel application for plasma lipids in cardiovascular risk screening of
      HIV-positive patients.

PMID- 24733513
TI  - Determination of pinocembrin in human plasma by solid-phase extraction and
      LC/MS/MS: application to pharmacokinetic studies.
AB  - A sensitive, fast and specific method for the quantitation of pinocembrin in
      human plasma based on high-performance liquid chromatography-tandem mass
      spectrometry (LC/MS/MS) was developed and validated. Clonazepam was used as the
      internal standard (IS). After solid-phase extraction of 500 MUL plasma,
      pinocembrin and the IS were separated on a Luna C8 column using the mobile phase
      composed of acetonitrile-0.3 mm ammonium acetate solution (65:35, v/v) at a flow
      rate of 0.25 mL/min in isocratic mode. The detection was performed on a triple
      quadrupole tandem mass spectrometer by multiple reaction monitoring via an
      electrospray ionization source in negative mode by AB SCIEX Qtrap 5500. The assay
      was linear from 1 to 400 ng/mL, with within- and between-run accuracy (relative
      error) from -1.82 to 0.54%, and within- and between-run precision (CV) below
      5.25%. The recovery was above 88% for the analyte at 1, 50 and 300 ng/mL. This
      analytical method was successful for the determination of pinocembrin in human
      plasma and applied to a pharmacokinetic study of pinocembrin injection in healthy
      volunteers after intravenous drip administration.

PMID- 24733515
TI  - Collaborative care intervention targeting violence risk behaviors, substance use,
      and posttraumatic stress and depressive symptoms in injured adolescents: a
      randomized clinical trial.
AB  - IMPORTANCE: Violence and injury risk behaviors, alcohol and drug use problems,
      and posttraumatic stress disorder (PTSD) and depressive symptoms occur frequently
      among adolescents presenting to acute care medical settings after traumatic
      physical injury. OBJECTIVE: To test the effectiveness of a stepped collaborative
      care intervention targeting this constellation of risk behaviors and symptoms in
      randomly sampled hospitalized adolescents with and without traumatic brain
      injury. DESIGN, SETTING, AND PARTICIPANTS: A pragmatic randomized clinical trial
      was conducted at a single US level I trauma center. Participants included 120
      adolescents aged 12 to 18 years randomized to intervention (n = 59) and control
      (n = 61) conditions. INTERVENTIONS: Stepped collaborative care intervention
      included motivational interviewing elements targeting risk behaviors and
      substance use as well as medication and cognitive behavioral therapy elements
      targeting PTSD and depressive symptoms. MAIN OUTCOMES AND MEASURES: Adolescents
      were assessed at baseline before randomization and 2, 5, and 12 months after
      injury hospitalization. Standardized instruments were used to assess violence
      risk behaviors, alcohol and drug use, and PTSD and depressive symptoms. RESULTS:
      The investigation attained more than 95% adolescent follow-up at each assessment
      point. At baseline, approximately one-third of the participants endorsed the
      violence risk behavior of carrying a weapon. Regression analyses demonstrated
      that intervention patients experienced significant reductions in weapon carrying
      compared with controls during the year after injury (group * time effect, F3,344
      = 3.0; P = .03). At 12 months after the injury, 4 (7.3%) intervention patients vs
      13 (21.3%) control patients reported currently carrying a weapon (relative risk,
      0.31; 95% CI, 0.11-0.90). The intervention was equally effective in reducing the
      risk of weapon carrying among injured adolescents with and without traumatic
      brain injury. Other treatment targets, including alcohol and drug use problems
      and high levels of PTSD and depressive symptoms, occurred less frequently in the
      cohort relative to weapon carrying and were not significantly affected by the
      intervention. CONCLUSIONS AND RELEVANCE: Collaborative care intervention reduced
      the risk of adolescent weapon carrying during the year after the injury
      hospitalization. Future investigation should replicate this preliminary
      observation. If the finding is replicated, orchestrated investigative and policy
      efforts could systematically implement and evaluate screening and intervention
      procedures targeting youth violence prevention at US trauma centers. TRIAL
      REGISTRATION: clinicaltrials.gov identifier: NCT00619255.

PMID- 24733517
TI  - Deletion of the Saccharomyces cerevisiae ARO8 gene, encoding an aromatic amino
      acid transaminase, enhances phenylethanol production from glucose.
AB  - Phenylethanol has a characteristic rose-like aroma that makes it a popular
      ingredient in foods, beverages and cosmetics. Microbial production of
      phenylethanol currently relies on whole-cell bioconversion of phenylalanine with
      yeasts that harbour an Ehrlich pathway for phenylalanine catabolism. Complete
      biosynthesis of phenylethanol from a cheap carbon source, such as glucose,
      provides an economically attractive alternative for phenylalanine bioconversion.
      In this study, synthetic genetic array (SGA) screening was applied to identify
      genes involved in regulation of phenylethanol synthesis in Saccharomyces
      cerevisiae. The screen focused on transcriptional regulation of ARO10, which
      encodes the major decarboxylase involved in conversion of phenylpyruvate to
      phenylethanol. A deletion in ARO8, which encodes an aromatic amino acid
      transaminase, was found to underlie the transcriptional upregulation of ARO10
      during growth, with ammonium sulphate as the sole nitrogen source. Physiological
      characterization revealed that the aro8Delta mutation led to substantial changes
      in the absolute and relative intracellular concentrations of amino acids.
      Moreover, deletion of ARO8 led to de novo production of phenylethanol during
      growth on a glucose synthetic medium with ammonium as the sole nitrogen source.
      The aro8Delta mutation also stimulated phenylethanol production when combined
      with other, previously documented, mutations that deregulate aromatic amino acid
      biosynthesis in S. cerevisiae. The resulting engineered S. cerevisiae strain
      produced >3 mm phenylethanol from glucose during growth on a simple synthetic
      medium. The strong impact of a transaminase deletion on intracellular amino acid
      concentrations opens new possibilities for yeast-based production of amino acid
      derived products.

PMID- 24733518
TI  - High hydrostatic pressure treatment provides persimmon good characteristics to
      formulate milk-based beverages with enhanced functionality.
AB  - High hydrostatic pressure (HHP) applied during food processing can improve the
      retention of food quality attributes and nutritional values in comparison with
      pasteurization. Persimmon is a good source of bioactive compounds but it is a
      seasonal fruit that cannot be consumed throughout the year. The aim of this work
      was to compare the HHP and pasteurization treatments to formulate milk-based
      beverages containing this carotenoid rich ingredient and to evaluate their
      performance in these beverages. The carotenoid and tannin contents of persimmon
      were determined and the microstructure and rheology of the new milk-based
      persimmon beverages were examined. The results showed that HHP treatment favoured
      the release of carotenoids from the fruit matrix and precipitation of the
      tannins. The milk-based beverages prepared with the high-pressure persimmon
      presented the best rheological properties because unlike the untreated and
      pasteurized persimmon milk-based beverages, they did not form a gel-like
      structure or separate out. 

PMID- 24733519
TI  - Triplet-triplet annihilation photon-upconversion: towards solar energy
      applications.
AB  - Solar power production and solar energy storage are important research areas for
      development of technologies that can facilitate a transition to a future society
      independent of fossil fuel based energy sources. Devices for direct conversion of
      solar photons suffer from poor efficiencies due to spectrum losses, which are
      caused by energy mismatch between the optical absorption of the devices and the
      broadband irradiation provided by the sun. In this context, photon-upconversion
      technologies are becoming increasingly interesting since they might offer an
      efficient way of converting low energy solar energy photons into higher energy
      photons, ideal for solar power production and solar energy storage. This
      perspective discusses recent progress in triplet-triplet annihilation (TTA)
      photon-upconversion systems and devices for solar energy applications.
      Furthermore, challenges with evaluation of the efficiency of TTA-photon
      upconversion systems are discussed and a general approach for evaluation and
      comparison of existing systems is suggested. 

PMID- 24733520
TI  - FAT-free p300 is good for scar-free tissue repair.
AB  - Fibrosis, the deadly pathological manifestation of an abnormal tissue remodeling
      in any organ due to excessive collagen deposition, is associated with a wide
      variety of organ failure-related human diseases. Chronic stress or repeated
      injury in a particular organ induces abnormal molecular signals that lead to
      super-activation of matrix protein producing fibroblasts, excessive matrix
      proteins accumulation, loss of physiological tissue architecture or elasticity,
      and ultimately leading to organ failure. There is no effective therapy for
      fibrosis. Factor acetyltransferase p300 (FATp300), a major epigenetic regulator
      that acetylates specific lysines in histones and transcription factors, is
      essential for elevated collagen synthesis and the levels of FATp300 are
      significantly elevated in different fibrotic tissues. Pharmacological inhibition
      of FAT activity of p300 is associated with decreased collagen synthesis by
      fibroblasts in tissues and amelioration of organ fibrosis. Therefore, FAT-free
      p300 is superior for physiological tissue repair and must be exploited as a
      viable therapeutic target against multi-organ fibrosis.

PMID- 24733521
TI  - In vivo characterisation of the inflammatory reaction following mesh implantation
      in transgenic mice models.
AB  - INTRODUCTION: Hernia repair with prosthetic meshes represents one of the most
      common surgical procedures in the field of surgery. This intervention is always
      associated with an ensuing inflammatory response, angiogenesis and fibrotic
      encapsulation forming a foreign body granuloma (FBG) around the mesh fibres.
      Several studies have described this inflammatory reaction by characterising
      inflammatory cell infiltrate around the FBG after mesh explantation. However,
      very little is known about the real-time progression of such an inflammatory
      response. The aim of this study was to investigate the feasibility of monitoring
      the ongoing inflammatory response to mesh implantation using bioluminescence in
      vivo. MATERIALS AND METHODS: Three luciferase transgenic mice strains (FVB/N
      Tg(Vegfr2-luc)-Xen, BALB/C-Tg(NFkappaB-RE-luc)-Xen and Tg(INS/EpRE-Luc)T20Rbl)
      were used. Mice were anaesthetized with 2 % isoflurane, and two incisions were
      made on the left and right sides of the abdomen of the mice. A 1-cm(2) propylene
      mesh was implanted subcutaneously in the right incision wound of each mouse, and
      the left wound served as control. Two hundred microliters of D-luciferin was
      injected into the mice, and bioluminescence measurements were done prior to the
      surgical intervention and subsequently every 3 days. After mesh explantation,
      histological analysis was done. Statistical analysis was done using prism
      GraphPad software. RESULTS: Bioluminescence results revealed different time
      points of maximum signal for the different mice strains. VEGFR2 gene expression
      peaked on day 6, NFkB on day 12 and ARE on day 3 post mesh implantation. We also
      observed much higher bioluminescent signal around the FBG surrounding the mesh as
      compared to the control wound, with p < 0.05 for all the different mice strains.
      CONCLUSION: Our results prove the possibility of monitoring the inflammatory
      reaction after mesh implantation in vivo using bioluminescence signal release.
      This provides a novel method of accessing and accurately describing the ongoing
      inflammatory response over a given period of time.

PMID- 24733522
TI  - Generating a dynamic synthetic population--using an age-structured two-sex model
      for household dynamics.
AB  - Generating a reliable computer-simulated synthetic population is necessary for
      knowledge processing and decision-making analysis in agent-based systems in order
      to measure, interpret and describe each target area and the human activity
      patterns within it. In this paper, both synthetic reconstruction (SR) and
      combinatorial optimisation (CO) techniques are discussed for generating a
      reliable synthetic population for a certain geographic region (in Australia)
      using aggregated- and disaggregated-level information available for such an area.
      A CO algorithm using the quadratic function of population estimators is presented
      in this paper in order to generate a synthetic population while considering a two
      fold nested structure for the individuals and households within the target areas.
      The baseline population in this study is generated from the confidentialised unit
      record files (CURFs) and 2006 Australian census tables. The dynamics of the
      created population is then projected over five years using a dynamic micro
      simulation model for individual- and household-level demographic transitions.
      This projection is then compared with the 2011 Australian census. A prediction
      interval is provided for the population estimates obtained by the bootstrapping
      method, by which the variability structure of a predictor can be replicated in a
      bootstrap distribution. 

PMID- 24733523
TI  - In vitro and in silico evaluation of NF-kappaB targeted costunolide action on
      estrogen receptor-negative breast cancer cells--a comparison with normal breast
      cells.
AB  - Costunolide, a sesquiterpene lactone is a plant-derived secondary metabolite
      found to be present in most of the pharmacologically active herbs, being the
      cause for their medicinal values. The present study aims to evaluate the
      cytotoxic effect of costunolide isolated from Costus speciosus rhizome extract on
      MDA-MB-231 cells and explore its targeted action in comparison with its action on
      the normal breast cells (MCF 10A). The effect of costunolide on cell viability of
      the cells was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium
      bromide viability assay. The targeted action of the compound was analyzed
      comparing the effectiveness of the compound to alter the protein expression
      levels of NF-kappaB subunits in the normal and the cancer cells using western
      blotting analysis. In silico studies were performed to predict the targeted
      interaction of costunolide with the NF-kappaB subunit proteins. Costunolide
      inhibited the cell viability of MDA-MB-231 cells in a dose-dependent manner
      leaving no significant change in the viability of the normal breast cells. The
      over expressed NF-kappaB subunits - p65, 52 and 100 in the cancer cells were
      found to be downregulated when treated with costunolide at an effective dose of
      20 and 40 MUM costunolide. In silico results provided stable interactions between
      costunolide and the target proteins, supporting the in vitro results in addition.
      Thus, costunolide derived from C. speciosus plant source elevates a fresh
      conviction for its use in breast cancer therapy for its cytotoxic efficacy and
      non-toxic nature.

PMID- 24733524
TI  - Employment barriers, skills, and aspirations among unemployed job seekers with
      and without social anxiety disorder.
AB  - OBJECTIVE: The literature has consistently demonstrated that social anxiety
      disorder has substantial negative impacts on occupational functioning. However,
      to date, no empirical work has focused on understanding the specific nature of
      vocational problems among persons with social anxiety disorder. This study
      examined the association between perceived barriers to employment, employment
      skills, and job aspirations and social anxiety among adults seeking vocational
      rehabilitation services. METHODS: Data from intake assessments (June 2010
      December 2011) of 265 low-income, unemployed adults who initiated vocational
      rehabilitation services in urban Michigan were examined to assess perceived
      barriers to employment, employment skills, job aspirations, and demographic
      characteristics among participants who did or did not screen positive for social
      anxiety disorder. Bivariate and multiple logistic regression analyses were
      performed. RESULTS: After adjustment for other factors, the multiple logistic
      regression analysis revealed that perceiving more employment barriers involving
      experience and skills, reporting fewer skills related to occupations requiring
      social skills, and having less education were significantly associated with
      social anxiety disorder. Participants who screened positive for social anxiety
      disorder were significantly less likely to aspire to social jobs. CONCLUSIONS:
      Employment-related characteristics that were likely to have an impact on
      occupational functioning were significantly different between persons with and
      without social anxiety problems. Identifying these differences in employment
      barriers, skills, and job aspirations revealed important information for
      designing psychosocial interventions for treatment of social anxiety disorder.
      The findings underscored the need for vocational services professionals to assess
      and address social anxiety among their clients.

PMID- 24733525
TI  - An efficient RFID authentication protocol to enhance patient medication safety
      using elliptic curve cryptography.
AB  - Medication errors are very dangerous even fatal since it could cause serious even
      fatal harm to patients. In order to reduce medication errors, automated patient
      medication systems using the Radio Frequency Identification (RFID) technology
      have been used in many hospitals. The data transmitted in those medication
      systems is very important and sensitive. In the past decade, many security
      protocols have been proposed to ensure its secure transition attracted wide
      attention. Due to providing mutual authentication between the medication server
      and the tag, the RFID authentication protocol is considered as the most important
      security protocols in those systems. In this paper, we propose a RFID
      authentication protocol to enhance patient medication safety using elliptic curve
      cryptography (ECC). The analysis shows the proposed protocol could overcome
      security weaknesses in previous protocols and has better performance. Therefore,
      the proposed protocol is very suitable for automated patient medication systems. 

PMID- 24733526
TI  - Chaos based encryption system for encrypting electroencephalogram signals.
AB  - In the paper, we use the Microsoft Visual Studio Development Kit and C#
      programming language to implement a chaos-based electroencephalogram (EEG)
      encryption system involving three encryption levels. A chaos logic map, initial
      value, and bifurcation parameter for the map were used to generate Level I chaos
      based EEG encryption bit streams. Two encryption-level parameters were added to
      these elements to generate Level II chaos-based EEG encryption bit streams. An
      additional chaotic map and chaotic address index assignment process was used to
      implement the Level III chaos-based EEG encryption system. Eight 16-channel EEG
      Vue signals were tested using the encryption system. The encryption was the most
      rapid and robust in the Level III system. The test yielded superior encryption
      results, and when the correct deciphering parameter was applied, the EEG signals
      were completely recovered. However, an input parameter error (e.g., a 0.00001 %
      initial point error) causes chaotic encryption bit streams, preventing the
      recovery of 16-channel EEG Vue signals.

PMID- 24733527
TI  - Unusual effects of solvent polarity on capacitance for organic electrolytes in a
      nanoporous electrode.
AB  - The interplay between ions and solvent molecules inside the nanoporous electrodes
      of a supercapacitor has not been well understood but could be a fertile ground
      for new insights into the device's performance. By tuning the dipole moment of
      the solvent in an organic electrolyte, we find, from classical density functional
      theory calculations, pronounced oscillation of capacitance with the pore size for
      a moderately to weakly polar solvent. A quantitative analysis of the electric
      double-layer (EDL) structure indicates that the capacitance oscillation shares a
      similar physical origin to that of an ionic liquid electrolyte: the oscillatory
      behavior arises from the formation of alternating layers of counterions and
      coions near strongly charged surfaces. More interestingly, we find that in the
      large-pore region, the capacitance versus the pore size has a volcano-shaped
      trend; in other words, there exists a solvent dipole moment that yields a maximal
      capacitance. These theoretical predictions can be validated with future
      experiments and highlight the great potential in tuning the organic solvent to
      achieve optimal performance of EDL capacitors. 

PMID- 24733528
TI  - Effects of Streptomyces pactum Act12 on Salvia miltiorrhiza hairy root growth and
      tanshinone synthesis and its mechanisms.
AB  - The fermentation broth and mycelium pellet of Streptomyces pactum Act12 (Act12)
      may promote the accumulation of soluble sugar when added to Salvia miltiorrhiza
      hairy roots, increasing the accumulation level by as much as 23.20 % compared
      with the control; it may also inhibit the accumulation of soluble protein in the
      hairy roots, decreasing it by as much as 17.96 % compared with the control. The
      ACT12 also has a certain promotional effect on the growth of hairy root at an
      appropriate concentration of elicitors and upregulates the expression of genes 3
      hydroxy-3-methyglutary1-CoA reductase (HMGR), 1-deoxy-D-xylulose 5-phosphate
      synthase (DXS), 1-deoxy-D-xylulose-5-phosphate reductoisomerase (DXR), and
      geranylgeranyl diphosphate synthase (GGPPS). Among these effects, that of the
      HMGR gene expression is as high as 33.66 times that of the control, indicating
      that the test Streptomyces pactum may efficiently adjust the secondary metabolism
      of S. miltiorrhiza at the level of gene transcription, thereby greatly increasing
      the accumulation level of tanshinone in the hairy roots; among which, the
      cryptotanshinone levels increased most significantly, as much as 33.63 times that
      of the control, and the total tanshinone levels were 12.61 times that of the
      control. 

PMID- 24733529
TI  - Enzymatic synthesis of gamma-glutamylmethylamide from glutamic acid gamma-methyl
      ester and methylamine catalyzed by Escherichia coli having gamma
      glutamyltranspeptidase activity.
AB  - A new method for the synthesis of gamma-glutamylmethylamide is presented.
      Glutamic acid gamma-methyl ester was used as substrate for gamma
      glutamylmethylamide synthesis catalyzed by Escherichia coli with gamma
      glutamyltranspeptidase activity. Reaction conditions were optimized by using 300
      mM glutamic acid gamma-methyl ester and 3,000 mM methylamine at pH 10 and 40 
      degrees C. Bioconversion rate of gamma-glutamylmethylamide reached 87 % after 10
      h. gamma-Glutamyltranspeptidase was reversibly inhibited only when glutamic acid
      gamma-methyl ester was above 300 mM. 

PMID- 24733530
TI  - Biosynthesis of glucosyl glycerol, a compatible solute, using intermolecular
      transglycosylation activity of amylosucrase from Methylobacillus flagellatus KT.
AB  - A putative alpha-amylase gene (accession number, CP000284) of Methylobacillus
      flagellatus KT ATCC51484 was cloned in Escherichia coli, and its gene product was
      expressed and characterized. The purified recombinant enzyme (MFAS) displayed a
      typical amylosucrase (ASase) activity by the demonstration of multiple activities
      of hydrolysis, isomerization, and polymerization although it was designated as an
      alpha-amylase. The optimal reaction temperature and pH for the sucrose hydrolysis
      activity of MFAS were determined to be 45  degrees C and pH 8.5, respectively.
      MFAS has relatively high thermostable characteristics compared with other ASases,
      as demonstrated by a half-life of 19.3 min at 50  degrees C. MFAS also showed
      polymerization activity using sucrose as a sole substrate. Glycerol was
      transglycosylated by the intermolecular transglycosylation activity of MFAS. Two
      major products were observed by thin-layer chromatography and isolated by paper
      chromatography and recycling HPLC. Using (1)H and (13)C NMR, their chemical
      structures were determined to be (2S)-1-O-alpha-D-glucosyl-glycerol or (2R)-1-O
      alpha-D-glucosyl-glycerol and 2-O-alpha-D-glucosyl-glycerol, in which a glucose
      molecule is linked to glycerol via an alpha-glycosidic linkage. 

PMID- 24733531
TI  - Waste Biogas residue from cassava dregs as carbon source to produce Galactomyces
      sp. Cczu11-1 cellulase and its enzymatic saccharification.
AB  - In the conversion of cassava starch dregs to biogas by anaerobic fermentation,
      the biogas residue (BR) containing lignocellulosic materials still remained in
      the environment. In order to effectively utilize BR, the complexed 1-methyl-3
      methylimidazolium dimethyl phosphate ([Mmim]DMP) media were used for pretreating
      cellulosic materials. After the optimization of pretreatment, the IL [Mmim]DMP
      HCl-water (78.5:1.5:20, w/w/w) pretreament media were used for pretreating BR at
      130  degrees C for 30 min. Furthermore, BR pretreated could be effectively
      saccharified by cellulase of Galactomyces sp. CCZU11-1. Moreover, BR could be
      used as a cheap carbon source for the production of Galactomyces sp. CCZU11-1
      cellulase. After the culture optimization, the optimal culture conditions were
      obtained as follows: BR 5 g/L, (NH4)2SO4 5 g/L, K2HPO4 2 g/L, MgSO4 0.2 g/L, NaCl
      1 g/L, PEG6000 4 g/L, pH 5.5, and culture temperature 30  degrees C. After the
      fermentation for 6 days, the FPA and CMCase were 26.2 and 52.8 U/mL,
      respectively. In conclusion, waste BR could be chosen as a promising feedstock
      for biofuels. 

PMID- 24733532
TI  - Improved production of poly-gamma-glutamic acid by Bacillus subtilis D7 isolated
      from Doenjang, a Korean traditional fermented food, and its antioxidant activity.
AB  - The objectives of this study was to improve poly-gamma-glutamic acid (gamma-PGA)
      production by Bacillus subtilis D7 isolated from a Korean traditional fermented
      food and to assess its antioxidant activity for applications in the cosmetics and
      pharmaceutical industries. Strain D7 produced gamma-PGA in the absence of L
      glutamic acid, indicating L-glutamic acid-independent production. However, the
      addition of L-glutamic acid increased gamma-PGA production. Several tricarboxylic
      acid cycle intermediates and amino acids could serve as the metabolic precursors
      for gamma-PGA production, and the addition of pyruvic acid and D-glutamic acid to
      culture medium improved the yield of gamma-PGA markedly. The maximum yield of
      gamma-PGA obtained was 24.93 +/- 0.64 g/l in improved medium, which was about 5.4
      fold higher than the yield obtained in basal medium. gamma-PGA was found to have
      1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity (46.8 +/- 1.5
      %), hydroxyl radical scavenging activity (52.0 +/- 1.8 %), 2,2'-azinobis-3
      ethylbenzothiazoline-6-sulfonate (ABTS) radical scavenging activity (42.1 +/- 1.8
      %), nitric oxide scavenging activity (35.1 +/- 1.3 %), reducing power (0.304 +/-
      0.008), and metal chelating activity (91.3 +/- 3.5 %). These results indicate
      that gamma-PGA has a potential use in the food, cosmetics, and biomedical
      industries for the development of novel products with radical scavenging
      activity. As far as we are aware, this is the first report to describe the
      antioxidant activityof gamma-PGA produced by bacteria. 

PMID- 24733533
TI  - Galactorrhea with menstrual irregularity: something other than a prolactinoma?
AB  - We report the case of a 29-year-old female who presented with galactorrhea and
      irregular menstrual periods. Laboratory tests showed elevated levels of serum
      prolactin, raising the possibility of a prolactinoma. However, further evaluation
      revealed an unusual and unexpected cause for her illness.

PMID- 24733534
TI  - Jejunal polyp: a rare cause of intussusception.

PMID- 24733535
TI  - Anticoagulation in atrial fibrillation.
AB  - Atrial fibrillation increases the risk of stroke, which is a leading cause of
      death and disability worldwide. The use of oral anticoagulation in patients with
      atrial fibrillation at moderate or high risk of stroke, estimated by established
      criteria, improves outcomes. However, to ensure that the benefits exceed the
      risks of bleeding, appropriate patient selection is essential. Vitamin K
      antagonism has been the mainstay of treatment; however, newer drugs with novel
      mechanisms are also available. These novel oral anticoagulants (direct thrombin
      inhibitors and factor Xa inhibitors) obviate many of warfarin's shortcomings, and
      they have demonstrated safety and efficacy in large randomized trials of patients
      with non-valvular atrial fibrillation. However, the management of patients taking
      warfarin or novel agents remains a clinical challenge. There are several
      important considerations when selecting anticoagulant therapy for patients with
      atrial fibrillation. This review will discuss the rationale for anticoagulation
      in patients with atrial fibrillation; risk stratification for treatment;
      available agents; the appropriate implementation of these agents; and additional,
      specific clinical considerations for treatment. 

PMID- 24733536
TI  - Routine treatment of patients with chronic lymphocytic leukaemia by office-based
      haematologists in Germany-data from the Prospective Tumour Registry Lymphatic
      Neoplasms.
AB  - Various treatment options exist for patients with chronic lymphocytic leukaemia
      (CLL). Clinical registries provide insight into routine treatment and identify
      changes in treatment over time. The Tumour Registry Lymphatic Neoplasms
      prospectively collects data on the treatment of patients with lymphoid B-cell
      neoplasm as administered by office-based haematologists in Germany. Data on
      patient and tumour characteristics, co-morbidities, systemic treatments, and
      outcome parameters are recorded. Eight hundred and six patients with CLL were
      recruited between May 2009 and August 2013. At the start of first-line treatment,
      median age was 71 years, 64% were male, and 44% had a Binet stage C disease. The
      most frequently used first-line/second-line regimens were bendamustine +
      rituximab (BR, 56%/55%), fludarabine + cyclophosphamide + rituximab (FCR,
      22%/11%), and bendamustine (B, 5%/9%). Chlorambucil was used in only 7% (first
      line) and 6% (second-line) of patients. Patients treated with FCR were younger
      and healthier than patients treated with BR. Overall, 91% of first-line
      treatments were successful (40% complete response). Real-life patient populations
      differ considerably from patients treated in randomized controlled trials. BR and
      FCR dominate the first-line and second-line treatments of CLL by office-based
      haematologists in Germany. Future analysis will investigate progression-free and
      overall survival times.

PMID- 24733537
TI  - Numerical and structural genomic aberrations are reliably detectable in tissue
      microarrays of formalin-fixed paraffin-embedded tumor samples by fluorescence in
      situ hybridization.
AB  - Few data are available regarding the reliability of fluorescence in-situ
      hybridization (FISH), especially for chromosomal deletions, in high-throughput
      settings using tissue microarrays (TMAs). We performed a comprehensive FISH study
      for the detection of chromosomal translocations and deletions in formalin-fixed
      and paraffin-embedded (FFPE) tumor specimens arranged in TMA format. We analyzed
      46 B-cell lymphoma (B-NHL) specimens with known karyotypes for translocations of
      IGH-, BCL2-, BCL6- and MYC-genes. Locus-specific DNA probes were used for the
      detection of deletions in chromosome bands 6q21 and 9p21 in 62 follicular
      lymphomas (FL) and six malignant mesothelioma (MM) samples, respectively. To test
      for aberrant signals generated by truncation of nuclei following sectioning of
      FFPE tissue samples, cell line dilutions with 9p21-deletions were embedded into
      paraffin blocks. The overall TMA hybridization efficiency was 94%. FISH results
      regarding translocations matched karyotyping data in 93%. As for chromosomal
      deletions, sectioning artefacts occurred in 17% to 25% of cells, suggesting that
      the proportion of cells showing deletions should exceed 25% to be reliably
      detectable. In conclusion, FISH represents a robust tool for the detection of
      structural as well as numerical aberrations in FFPE tissue samples in a TMA-based
      high-throughput setting, when rigorous cut-off values and appropriate controls
      are maintained, and, of note, was superior to quantitative PCR approaches. 

PMID- 24733538
TI  - Teaching psychiatry residents to work at the interface of mental health and
      primary care.
AB  - The authors present examples of programs educating psychiatry residents to work
      in integrated healthcare settings. 

PMID- 24733539
TI  - Don't judge books by their covers: vascular smooth muscle cells in arterial
      pathologies.

PMID- 24733542
TI  - Multidetector computed tomographic angiography imaging of pentalogy of Cantrell.

PMID- 24733540
TI  - Standardizing clinical end points in aortic arch surgery: a consensus statement
      from the International Aortic Arch Surgery Study Group.

PMID- 24733543
TI  - Osler node.

PMID- 24733544
TI  - Update: shortness of breath.

PMID- 24733545
TI  - Letter by Correia et al regarding article, "stress cardiac magnetic resonance
      imaging provides effective cardiac risk reclassification in patients with known
      or suspected stable coronary artery disease".

PMID- 24733546
TI  - Response to letter regarding article, "stress cardiac magnetic resonance imaging
      provides effective cardiac risk reclassification in patients with known or
      suspected stable coronary artery disease".

PMID- 24733548
TI  - Reducing the dietary omega-6:omega-3 utilizing alpha-linolenic acid; not a
      sufficient therapy for attenuating high-fat-diet-induced obesity development nor
      related detrimental metabolic and adipose tissue inflammatory outcomes.
AB  - AIMS: To examine the effect of manipulating the omega-6:omega-3 (1?1, 5?1, 10?1,
      and 20?1) utilizing only alpha-linolenic and linoleic acid within a clinically
      relevant high-fat diet (HFD) composed of up to seven sources of fat and designed
      to be similar to the standard American diet (MUFA?PUFA of 2?1, 12% and 40% of
      calories from saturated and total fat, respectively) on body composition,
      macrophage polarization, inflammation, and metabolic dysfunction in mice.
      METHODS: Diets were administered for 20 weeks. Body composition and metabolism
      (HOMA index and lipid profile) were examined monthly. GC-MS was utilized to
      determine the eicosapentaenoic acid (EPA):arachidonic acid (AA) and the
      docosahexaenoic acid (DHA):AA in AT phospholipids. Adipose tissue (AT) mRNA
      expression of chemokines (MCP-1, Fetuin-A, CXCL14), marker genes for M1 and M2
      macrophages (CD11c and CD206, respectively) and inflammatory markers (TNF-alpha,
      IL-6, IL-1beta, TLR-2, TLR-4, IL-10, GPR120) were measured along with activation
      of NFkappaB, JNK, and STAT-3. Macrophage infiltration into AT was examined using
      F4/80 immunohistochemistry. RESULTS: Any therapeutic benefit produced by reducing
      the omega-6:omega-3 was evident only when comparing the 1?1 to 20?1 HFD; the 1?1
      HFD resulted in a lower TC:HDL-C and decreased AT CXCL14 gene expression and AT
      macrophage infiltration, which was linked to a higher EPA:AA and DHA:AA in AT
      phospholipids. However, despite these effects, and independent of the omega
      6:omega-3, all HFDs, in general, led to similar levels of adiposity, insulin
      resistance, and AT inflammation. CONCLUSION: Reducing the omega-6:omega-3 using
      alpha-linolenic acid is not an effective therapy for attenuating obesity and type
      II diabetes mellitus development.

PMID- 24733549
TI  - Down-regulation of FcepsilonRI-mediated CD63 basophil response during short-term
      VIT determined venom-nonspecific desensitization.
AB  - BACKGROUND: We recently showed a desensitization of FcepsilonRI-mediated basophil
      response after short-term VIT. Our aim was to evaluate the allergen specificity
      of this desensitization. METHODS: In 11 Hymenoptera-venom double positive
      subjects, basophil threshold sensitivity (CD-sens) to anti-FcepsilonRI, honeybee,
      and Vespula venom was assessed at the beginning and just before the first
      maintenance dose (MD) of single ultra-rush VIT. In some patients we also
      monitored CD-sens to rApi m 1 and/or rVes v 5 or other co-sensitizations (i.e.,
      grass pollen). In additional 7 patients, basophils were stripped and sensitized
      with house dust mite (HDM) IgEs at the same time points. RESULTS: We demonstrated
      a marked reduction of CD-sens to anti-FcepsilonRI and VIT-specific venom before
      the first MD in all 18 subjects included. Furthermore, in 10 out of 11 double
      positive subjects, a significant and comparable decrease before the first MD was
      also evident for non-VIT venom; this nonspecific decrease was further supported
      by the opposite recombinant species-specific major allergen. In one subject with
      additional grass pollen allergy, a decrease of CD-sens to grass allergen was also
      demonstrated. Similarly, in 7 cases of patients with passively HDM-sensitized
      basophils, a significant reduction of CD-sens was also evident to de novo
      sensitized HDM allergen. CONCLUSIONS: Short-term VIT induced basophil
      desensitization to VIT-specific as well as to VIT-nonspecific venom. As opposed
      to long-term VIT, which induces venom-specific changes, the effect of short-term
      VIT seems to be venom-nonspecific.

PMID- 24733550
TI  - The role of therapeutic leukapheresis in hyperleukocytotic AML.
AB  - PURPOSE: Hyperleukocytosis in AML with leukostasis is a serious life-threatening
      condition leading to a high early mortality which requires immediate
      cytoreductive therapy. Therapeutic leukapheresis is currently recommended by the
      American Society of Apheresis in patients with a WBC>100 G/l with signs of
      leukostasis, but the role of prophylactic leukapheresis before clinical signs of
      leukostasis occur is unclear. PATIENTS: We retrospectively analyzed the role of
      leukapheresis in 52 patients (median age 60 years) with hyperleukocytotic AML
      with and without clinical signs of leukostasis. Since leukapheresis was performed
      more frequently in patients with signs of leukostasis due to the therapeutic
      policy in our hospital, we developed a risk score for early death within seven
      days after start of therapy (EDd7) to account for this selection bias and to
      independently measure the effect of leukapheresis on EDd7. RESULTS: 20 patients
      received leukapheresis in combination to chemotherapy compared to 32 patients who
      received chemotherapy only. In a multivariate logistic regression model for the
      estimation of the probability of EDd7 thromboplastin time and creatinine remained
      as independent significant parameters and were combined to create an EDd7 risk
      score. The effect of leukapheresis on EDd7 was evaluated in a bivariate logistic
      regression together with the risk score. Leukapheresis did not significantly
      change early mortality in all patients with a WBC>=100 G/l. DISCUSSION:
      Prophylactic leukapheresis in hyperleukocytotic patients with and without
      leukostasis did not improve early mortality in our retrospective study. Larger
      and prospective clinical trials are needed to validate the risk score and to
      further explore the role of leukapheresis in AML with hyperleukocytosis.

PMID- 24733551
TI  - Effects of prolonged exposure to hypobaric hypoxia on oxidative stress,
      inflammation and gluco-insular regulation: the not-so-sweet price for good
      regulation.
AB  - OBJECTIVES: The mechanisms by which low oxygen availability are associated with
      the development of insulin resistance remain obscure. We thus investigated the
      relationship between such gluco-insular derangements in response to sustained
      (hypobaric) hypoxemia, and changes in biomarkers of oxidative stress,
      inflammation and counter-regulatory hormone responses. METHODS: After baseline
      testing in London (75 m), 24 subjects ascended from Kathmandu (1,300 m) to
      Everest Base Camp (EBC;5,300 m) over 13 days. Of these, 14 ascended higher, with
      8 reaching the summit (8,848 m). Assessments were conducted at baseline, during
      ascent to EBC, and 1, 6 and 8 week(s) thereafter. Changes in body weight and
      indices of gluco-insular control were measured (glucose, insulin, C-Peptide,
      homeostasis model assessment of insulin resistance [HOMA-IR]) along with
      biomarkers of oxidative stress (4-hydroxy-2-nonenal-HNE), inflammation
      (Interleukin-6 [IL-6]) and counter-regulatory hormones (glucagon, adrenalin,
      noradrenalin). In addition, peripheral oxygen saturation (SpO2) and venous blood
      lactate concentrations were determined. RESULTS: SpO2 fell significantly from
      98.0% at sea level to 82.0% on arrival at 5,300 m. Whilst glucose levels remained
      stable, insulin and C-Peptide concentrations increased by >200% during the last 2
      weeks. Increases in fasting insulin, HOMA-IR and glucagon correlated with
      increases in markers of oxidative stress (4-HNE) and inflammation (IL-6). Lactate
      levels progressively increased during ascent and remained significantly elevated
      until week 8. Subjects lost on average 7.3 kg in body weight. CONCLUSIONS:
      Sustained hypoxemia is associated with insulin resistance, whose magnitude
      correlates with the degree of oxidative stress and inflammation. The role of 4
      HNE and IL-6 as key players in modifying the association between sustained
      hypoxia and insulin resistance merits further investigation.

PMID- 24733552
TI  - Linked production of pyroglutamate-modified proteins via self-cleavage of fusion
      tags with TEV protease and autonomous N-terminal cyclization with glutaminyl
      cyclase in vivo.
AB  - Overproduction of N-terminal pyroglutamate (pGlu)-modified proteins utilizing
      Escherichia coli or eukaryotic cells is a challenging work owing to the fact that
      the recombinant proteins need to be recovered by proteolytic removal of fusion
      tags to expose the N-terminal glutaminyl or glutamyl residue, which is then
      converted into pGlu catalyzed by the enzyme glutaminyl cyclase. Herein we
      describe a new method for production of N-terminal pGlu-containing proteins in
      vivo via intracellular self-cleavage of fusion tags by tobacco etch virus (TEV)
      protease and then immediate N-terminal cyclization of passenger target proteins
      by a bacterial glutaminyl cyclase. To combine with the sticky-end PCR cloning
      strategy, this design allows the gene of target proteins to be efficiently
      inserted into the expression vector using two unique cloning sites (i.e., SnaB I
      and Xho I), and the soluble and N-terminal pGlu-containing proteins are then
      produced in vivo. Our method has been successfully applied to the production of
      pGlu-modified enhanced green fluorescence protein and monocyte chemoattractant
      proteins. This design will facilitate the production of protein drugs and drug
      target proteins that possess an N-terminal pGlu residue required for their
      physiological activities. 

PMID- 24733553
TI  - Predicting rotator cuff tears using data mining and Bayesian likelihood ratios.
AB  - OBJECTIVES: Rotator cuff tear is a common cause of shoulder diseases. Correct
      diagnosis of rotator cuff tears can save patients from further invasive, costly
      and painful tests. This study used predictive data mining and Bayesian theory to
      improve the accuracy of diagnosing rotator cuff tears by clinical examination
      alone. METHODS: In this retrospective study, 169 patients who had a preliminary
      diagnosis of rotator cuff tear on the basis of clinical evaluation followed by
      confirmatory MRI between 2007 and 2011 were identified. MRI was used as a
      reference standard to classify rotator cuff tears. The predictor variable was the
      clinical assessment results, which consisted of 16 attributes. This study
      employed 2 data mining methods (ANN and the decision tree) and a statistical
      method (logistic regression) to classify the rotator cuff diagnosis into "tear"
      and "no tear" groups. Likelihood ratio and Bayesian theory were applied to
      estimate the probability of rotator cuff tears based on the results of the
      prediction models. RESULTS: Our proposed data mining procedures outperformed the
      classic statistical method. The correction rate, sensitivity, specificity and
      area under the ROC curve of predicting a rotator cuff tear were statistical
      better in the ANN and decision tree models compared to logistic regression. Based
      on likelihood ratios derived from our prediction models, Fagan's nomogram could
      be constructed to assess the probability of a patient who has a rotator cuff tear
      using a pretest probability and a prediction result (tear or no tear).
      CONCLUSIONS: Our predictive data mining models, combined with likelihood ratios
      and Bayesian theory, appear to be good tools to classify rotator cuff tears as
      well as determine the probability of the presence of the disease to enhance
      diagnostic decision making for rotator cuff tears.

PMID- 24733554
TI  - Development of genetically flexible mouse models of sarcoma using RCAS-TVA
      mediated gene delivery.
AB  - Sarcomas are a heterogeneous group of mesenchymal malignancies and unfortunately
      there are limited functional genomics platforms to assess the molecular pathways
      contributing to sarcomagenesis. Thus, novel model systems are needed to validate
      which genes should be targeted for therapeutic intervention. We hypothesized that
      delivery of oncogenes into mouse skeletal muscle using a retroviral (RCAS-TVA)
      system would result in sarcomagenesis. We also sought to determine if the cell
      type transformed (mesenchymal progenitors vs. terminally differentiated tissues)
      would influence sarcoma biology. Cells transduced with RCAS vectors directing the
      expression of oncoproteins KrasG12D, c-Myc and/or Igf2 were injected into the
      hindlimbs of mice that expressed the retroviral TVA receptor in
      neural/mesenchymal progenitors, skeletal/cardiac muscle or ubiquitously (N-tva,
      AKE and BKE strains respectively). Disrupting the G1 checkpoint CDKN2 (p16/p19-/
      ) resulted in sarcoma in 30% of p16/p19-/- xN-tva mice with a median latency of
      23 weeks (range 8-40 weeks). A similar incidence occurred in p16/p19-/- xBKE mice
      (32%), however, a shorter median latency (10.4 weeks) was observed. p16/p19-/-
      xAKE mice also developed sarcomas (24% incidence; median 9 weeks) yet 31% of mice
      also developed lung sarcomas. Gene-anchored PCR demonstrated retroviral DNA
      integration in 86% of N-tva, 93% of BKE and 88% of AKE tumors. KrasG12D was the
      most frequent oncogene isolated. Oncogene delivery by the RCAS-TVA system can
      generate sarcomas in mice with a defective cell cycle checkpoint. Sarcoma biology
      differed between the different RCAS models we created, likely due to the cell
      population being transformed. This genetically flexible system will be a valuable
      tool for sarcoma research.

PMID- 24733555
TI  - A modified screening system for loss-of-function and dominant negative alleles of
      essential MCMV genes.
AB  - Inactivation of gene products by dominant negative mutants is a valuable tool to
      assign functions to yet uncharacterized proteins, to map protein-protein
      interactions or to dissect physiological pathways. Detailed functional and
      structural knowledge about the target protein would allow the construction of
      inhibitory mutants by targeted mutagenesis. Yet, such data are limited for the
      majority of viral proteins, so that the target gene needs to be subjected to
      random mutagenesis to identify suitable mutants. However, for cytomegaloviruses
      this requires a two-step screening approach, which is time-consuming and labor
      intensive. Here, we report the establishment of a high-throughput suitable
      screening system for the identification of inhibitory alleles of essential genes
      of the murine cytomegalovirus (MCMV). In this screen, the site-specific
      recombination of a specifically modified MCMV genome was transferred from the
      bacterial background to permissive host cells, thereby combining the genetic
      engineering and the rescue test in one step. Using a reference set of
      characterized pM53 mutants it was shown that the novel system is applicable to
      identify non-complementing as well as inhibitory mutants in a high-throughput
      suitable setup. The new cis-complementation assay was also applied to a basic
      genetic characterization of pM99, which was identified as essential for MCMV
      growth. We believe that the here described novel genetic screening approach can
      be adapted for the genetic characterization of essential genes of any large DNA
      viruses. 

PMID- 24733556
TI  - Staphylococcus aureus alpha-toxin mediates general and cell type-specific changes
      in metabolite concentrations of immortalized human airway epithelial cells.
AB  - Staphylococcus aureus alpha-toxin (Hla) is a potent pore-forming cytotoxin that
      plays an important role in the pathogenesis of S. aureus infections, including
      pneumonia. The impact of Hla on the dynamics of the metabolome in eukaryotic host
      cells has not been investigated comprehensively. Using 1H-NMR, GC-MS and HPLC-MS,
      we quantified the concentrations of 51 intracellular metabolites and assessed
      alterations in the amount of 25 extracellular metabolites in the two human
      bronchial epithelial cell lines S9 and 16HBE14o- under standard culture
      conditions and after treatment with sub-lethal amounts (2 ug/ml) of recombinant
      Hla (rHla) in a time-dependent manner. Treatment of cells with rHla caused
      substantial decreases in the concentrations of intracellular metabolites from
      different metabolic pathways in both cell lines, including ATP and amino acids.
      Concomitant increases in the extracellular concentrations were detected for
      various intracellular compounds, including nucleotides, glutathione disulfide and
      NAD+. Our results indicate that rHla has a major impact on the metabolome of
      eukaryotic cells as a consequence of direct rHla-mediated alterations in plasma
      membrane permeability or indirect effects mediated by cellular signalling.
      However, cell-specific changes also were observed. Glucose consumption and
      lactate production rates suggest that the glycolytic activity of S9 cells, but
      not of 16HBE14o- cells, is increased in response to rHla. This could contribute
      to the observed higher level of resistance of S9 cells against rHla-induced
      membrane damage. 

PMID- 24733558
TI  - DNA as a phosphate storage polymer and the alternative advantages of polyploidy
      for growth or survival.
AB  - Haloferax volcanii uses extracellular DNA as a source for carbon, nitrogen, and
      phosphorous. However, it can also grow to a limited extend in the absence of
      added phosphorous, indicating that it contains an intracellular phosphate storage
      molecule. As Hfx. volcanii is polyploid, it was investigated whether DNA might be
      used as storage polymer, in addition to its role as genetic material. It could be
      verified that during phosphate starvation cells multiply by distributing as well
      as by degrading their chromosomes. In contrast, the number of ribosomes stayed
      constant, revealing that ribosomes are distributed to descendant cells, but not
      degraded. These results suggest that the phosphate of phosphate-containing
      biomolecules (other than DNA and RNA) originates from that stored in DNA, not in
      rRNA. Adding phosphate to chromosome depleted cells rapidly restores polyploidy.
      Quantification of desiccation survival of cells with different ploidy levels
      showed that under phosphate starvation Hfx. volcanii diminishes genetic
      advantages of polyploidy in favor of cell multiplication. The consequences of the
      usage of genomic DNA as phosphate storage polymer are discussed as well as the
      hypothesis that DNA might have initially evolved in evolution as a storage
      polymer, and the various genetic benefits evolved later. 

PMID- 24733559
TI  - Sources of the increasing number of Vietnam era veterans with a diagnosis of PTSD
      using VHA services.
AB  - OBJECTIVE: Correlates of the sharp increase in Vietnam era veterans diagnosed as
      having posttraumatic stress disorder (PTSD) in the Veterans Health Administration
      (VHA) were examined. METHODS: Analyses compared receipt of a PTSD diagnosis and
      service-connected disability compensation in 2004-2006 and 2007-2009. RESULTS:
      Among Vietnam era veterans, the percentage with a PTSD diagnosis in 2007-2009 was
      22.2% higher than the percentage with PTSD in 2004-2006; the percentage without
      PTSD was 6.2% higher than in 2004-2006. Of those with PTSD in 2007-2009, 22.6%
      were previous VHA service users newly diagnosed ("conversions"); only 12.8% were
      entirely new to VHA ("recents"). Rates of disability compensation among recents
      and conversions were almost two and three times higher, respectively, than among
      those without PTSD. CONCLUSIONS: The increase in Vietnam era veterans with PTSD
      is associated with more frequent "conversion" to PTSD among previous VHA users
      and receipt of disability compensation.

PMID- 24733557
TI  - PI3K/Akt-independent NOS/HO activation accounts for the facilitatory effect of
      nicotine on acetylcholine renal vasodilations: modulation by ovarian hormones.
AB  - We investigated the effect of chronic nicotine on cholinergically-mediated renal
      vasodilations in female rats and its modulation by the nitric oxide synthase
      (NOS)/heme oxygenase (HO) pathways. Dose-vasodilatory response curves of
      acetylcholine (0.01-2.43 nmol) were established in isolated phenylephrine
      preconstricted perfused kidneys obtained from rats treated with or without
      nicotine (0.5-4.0 mg/kg/day, 2 weeks). Acetylcholine vasodilations were
      potentiated by low nicotine doses (0.5 and 1 mg/kg/day) in contrast to no effect
      for higher doses (2 and 4 mg/kg/day). The facilitatory effect of nicotine was
      acetylcholine specific because it was not observed with other vasodilators such
      as 5'-N-ethylcarboxamidoadenosine (NECA, adenosine receptor agonist) or
      papaverine. Increases in NOS and HO-1 activities appear to mediate the nicotine
      evoked enhancement of acetylcholine vasodilation because the latter was
      compromised after pharmacologic inhibition of NOS (L-NAME) or HO-1 (zinc
      protoporphyrin, ZnPP). The renal protein expression of phosphorylated Akt was not
      affected by nicotine. We also show that the presence of the two ovarian hormones
      is necessary for the nicotine augmentation of acetylcholine vasodilations to
      manifest because nicotine facilitation was lost in kidneys of ovariectomized
      (OVX) and restored after combined, but not individual, supplementation with
      medroxyprogesterone acetate (MPA) and estrogen (E2). Together, the data suggests
      that chronic nicotine potentiates acetylcholine renal vasodilation in female rats
      via, at least partly, Akt-independent HO-1 upregulation. The facilitatory effect
      of nicotine is dose dependent and requires the presence of the two ovarian
      hormones. 

PMID- 24733561
TI  - Loss of nuclear prothymosin-alpha expression is associated with disease
      progression in human superficial bladder cancer.
AB  - In this paper, we report a study on the clinical relevance of prothymosin-alpha
      expression and its correlation with intratumoral Foxp3(+) and CD8(+) lymphocytes
      (Foxp3(+)TIL and CD8(+)TIL) in bladder cancer patients. We used
      immunohistochemical staining for prothymosin-alpha, Foxp3, and CD8 on 101 tumor
      specimens harvested by endoscopic resection. The results were correlated with
      clinicopathological variables and clinical outcome in bladder cancer patients,
      particularly in 73 patients with superficial disease, using the log-rank test and
      Cox proportional hazard model. Overall, of the tumors, 30 % were negative, 34 %
      showed nuclear, and 37 % showed cytoplasmic prothymosin-alpha expression.
      Foxp3(+)TILs were detected in 11 % of patients (nonnuclear vs. nuclear, p =
      0.096). Patients with a history of urothelial carcinoma have a higher frequency
      of nonnuclear prothymosin-alpha expression than those without (p = 0.016, chi
      square test). By univariate and multivariate analyses of cases with superficial
      disease, grade and stage were identified as independent predictors for recurrence
      free survival (p = 0.016 and 0.016, respectively). Higher stage and nonnuclear
      prothymosin-alpha expression independently predict shorter progression-free
      survival (p = 0.006 and 0.043, respectively). The presence of Foxp3(+)TILs was
      significantly associated with disease progression by univariate analysis (p =
      0.022), but not by multivariate analysis (p = 0.147). In vitro assays showed that
      J82 cells which express ectopically nuclear prothymosin-alpha exhibit higher
      growth rate and secrete less TGF-beta1 than those with cytoplasmic expression or
      control cells. Altogether, prothymosin-alpha expression is a determinant of
      disease progression in superficial bladder cancer. Foxp3(+)TILs tend to be found
      more often in bladder cancer with nonnuclear prothymosin-alpha expression. Future
      study is required to unravel their interaction. 

PMID- 24733562
TI  - Beclin-1 is required for RANKL-induced osteoclast differentiation.
AB  - Beclin-1 plays a critical role in autophagy; however, it also contributes to
      other biological processes in a non-autophagic manner. Although studies have
      examined the non-autophagic role of autophagy proteins in the secretory function
      of osteoclasts (OC), the role of Beclin-1 is unclear. Here, we examined the role
      of Beclin-1 in OC differentiation, and found that mouse bone marrow macrophages
      (BMMs) showed increased expression of Beclin-1 upon RANKL stimulation in a p38-
      and NF-kappa B-dependent manner. During OC differentiation, Beclin-1 localized to
      the mitochondria, where it was involved in the production of mitochondrial
      intracellular reactive oxygen species. Knockdown of Beclin-1 in RANKL-primed BMMs
      led to a significant reduction in RANKL-dependent osteoclastogenesis, which was
      accompanied by reduced NFATc1 induction. Furthermore, knockdown of Beclin-1
      inhibited RANKL-mediated activation of JNK and p38, both of which act downstream
      of reactive oxygen species, resulting in the suppression of NFATc1 induction.
      Finally, overexpression of constitutively active NFATc1 rescued the phenotype
      induced by Beclin-1 knockdown, indicating that Beclin-1 mediates RANKL-induced
      osteoclastogenesis by regulating NFATc1 expression. These findings show that
      Beclin-1 plays a non-autophagic role in RANKL-induced osteoclastogenesis by
      inducing the production of reactive oxygen species and NFATc1.

PMID- 24733563
TI  - Unraveling manganese dissolution/deposition mechanisms on the negative electrode
      in lithium ion batteries.
AB  - The structure, chemistry, and spatial distribution of Mn-bearing nanoparticles
      dissolved from the Li1.05Mn2O4 cathode during accelerated electrochemical cycling
      tests at 55  degrees C and deposited within the solid electrolyte interphase
      (SEI) are directly characterized through HRTEM imaging and XPS. Here we use air
      protection and vacuum transfer systems to transport cycled electrodes for imaging
      and analytical characterization. From HRTEM imaging, we find that a band of
      individual metallic Mn nanoparticles forms locally at the SEI/graphite interface
      while the internal and outermost layer of the SEI contains a mixture of LiF and
      MnF2 nanoparticles, which is confirmed with XPS. Based on our experimental
      findings we propose a new interpretation of how Mn is reduced from the cathode
      and how metallic Mn and Mn-bearing nanoparticles form within the SEI during
      electrochemical cycling. 

PMID- 24733560
TI  - Immune escape of gamma-herpesviruses from adaptive immunity.
AB  - Epstein-Barr virus (EBV) and Kaposi's sarcoma-associated herpesvirus (KSHV) are
      two gamma-herpesviruses identified in humans and are strongly associated with the
      development of malignancies. Murine gamma-herpesvirus (MHV-68) is a naturally
      occurring rodent pathogen, representing a unique experimental model for
      dissecting gamma-herpesvirus infection and the immune response. These gamma
      herpesviruses actively antagonize the innate and adaptive antiviral responses,
      thereby efficiently establishing latent or persistent infections and even
      promoting development of malignancies. In this review, we summarize immune
      evasion strategies of gamma-herpesviruses. These include suppression of MHC-I
      restricted and MHC-II-restricted antigen presentation, impairment of dendritic
      cell functions, downregulation of costimulatory molecules, activation of virus
      specific regulatory T cells, and induction of inhibitory cytokines. There is a
      focus on how both gamma-herpesvirus-derived and host-derived immunomodulators
      interfere with adaptive antiviral immunity. Understanding immune-evasive
      mechanisms is essential for developing future immunotherapies against EBV-driven
      and KSHV-driven tumors.

PMID- 24733564
TI  - Nationwide neonatal screening for congenital adrenal hyperplasia in sweden: a 26
      year longitudinal prospective population-based study.
AB  - IMPORTANCE: Recent reports have questioned the rationale for neonatal screening
      for congenital adrenal hyperplasia (CAH) owing to low sensitivity in salt-wasting
      forms and a high rate of recall (ie, a positive finding resulting in a visit to a
      pediatrician and a second test) in preterm infants. OBJECTIVE: To determine the
      efficiency of the neonatal screening program for CAH in Sweden over time. DESIGN,
      SETTING, AND PARTICIPANTS: Longitudinal prospective population-based study in
      Sweden. We assessed neonatal screening for CAH from January 1, 1986, through
      December 31, 2011, when 2 737 932 infants (99.8%) underwent testing. The CYP21A2
      genotype was investigated in 219 cases with true-positive findings (94.8%). We
      investigated the screening outcomes for 231 patients who had true-positive
      findings, 43 with late diagnosis, and 1497 infants with false-positive findings.
      MAIN OUTCOMES AND MEASURES: Sensitivity of the screening for salt-wasting CAH.
      The most important secondary outcome measures were the positive predictive values
      and recall rates for full-term and preterm infants and sensitivity for milder
      forms of CAH. RESULTS: A total of 143 patients with salt-wasting CAH were
      identified; none were missed. The sensitivity was lower for milder forms of the
      disorder (P = .04), including 79.7% for simple virilizing forms and 32.4% for
      nonclassic forms. The positive predictive value was higher in full-term (25.1%)
      than preterm (1.4%) infants and correlated with gestational age (r = 0.98; P <
      .001). The recall rate in full-term infants (0.03%) was lower than that in
      preterm infants (0.57%) (P < .001). An analysis of previously reported results
      from other screening programs revealed that the sensitivity of the screening was
      negatively correlated with the duration of follow-up (P = .03). CONCLUSIONS AND
      RELEVANCE: Screening for CAH was highly effective in detecting the salt-wasting
      form and thereby reducing mortality. Additional late-onset cases of CAH were
      detected in childhood and adolescence, reducing the sensitivity for milder forms.
      The positive predictive value was high despite a low recall rate in full-term
      infants. Further improvements are necessary to increase the effectiveness of
      screening among preterm infants.

PMID- 24733565
TI  - Unusual polyposis in ulcerative colitis.

PMID- 24733566
TI  - Determination of free serotonin and its metabolite 5-HIAA in blood human samples
      with consideration to pre-analytical factors.
AB  - Significant differences have been reported over the years in measuring
      physiological levels of free circulating serotonin (f5-HT) in platelet-poor
      plasma (PPP). This work shows that there are crucial pre-analytical factors in
      sample manipulation that can provoke an artifactual release of 5-HT from
      platelets, and that, even when the sample is accurately processed to obtain PPP,
      f5-HT levels are approximately 2.8 times higher than those of f5-HT in blood. An
      alternative methodology consisting of ex vivo blood microdialysis coupled to high
      performance liquid chromatography-electrochemical detection is proposed and
      validated. It is considered the most accurate technique to measure physiological
      circulating f5-HT and its metabolite 5-hydroxyindoleacetic acid (f5-HIAA), owing
      to its sensitivity (limits of quantification of 0.08 ng/mL) and reliability since
      there is no sample manipulation. The f5-HT and f5-HIAA levels in blood and in PPP
      were studied in control subjects, hypertensive and end-stage renal disease
      patients, who have a deregulated serotonergic system. This work reveals that
      blood is the best matrix to determine f5-HT concentrations, and the clinical
      relevance of the accuracy of f5-HT determination is discussed.

PMID- 24733567
TI  - Zearalenone exposure affects mouse oocyte meiotic maturation and granulosa cell
      proliferation.
AB  - Zearalenone (ZEN) is a metabolite of Fusarium and is a common contaminant of
      grains and foodstuffs. ZEN acts as a xenoestrogen and is considered to be
      cytotoxic, tissue toxic, and genotoxic, which causes abortions and stillbirths in
      humans and animals. Since estrogens affect oocyte maturation during meiosis, in
      this study we investigated the effects of ZEN on mouse oocyte meiotic maturation
      and granulosa cell proliferation. Our results showed that ZEN-treated oocyte
      maturation rates were decreased, which might be due to the disrupted
      cytoskeletons: (1) ZEN treatment resulted in significantly more oocytes with
      abnormal spindle morphologies; (2) actin filament expression and distribution
      were also disrupted after ZEN treatment, which was confirmed by the aberrant
      distribution of actin regulatory proteins. In addition, cortical granule-free
      domains (CGFDs) were disrupted after ZEN treatment, which indicated that ZEN may
      affect mouse oocyte fertilization capability. ZEN reduced mouse granulosa cell
      proliferation in a dose-dependent manner as determined by MTT assay and TUNEL
      apoptosis analysis, which may be another cause for the decreased oocyte
      maturation. Thus, our results demonstrated that exposure to zearalenone affected
      oocyte meiotic maturation and granulosa cell proliferation in mouse.

PMID- 24733568
TI  - A systematic review of randomized controlled trials testing the efficacy of
      psychosocial interventions for gastrointestinal cancers.
AB  - INTRODUCTION: Psychological morbidity in those diagnosed with cancer has been
      shown to result in poorer quality of life and increase the risk of mortality. As
      a result, researchers have designed and tested psychosocial interventions to
      improve quality of life and survival of patients diagnosed with cancer. METHODS:
      A systematic review of the literature was performed to describe the psychosocial
      interventions that have been tested in patients with gastrointestinal cancers.
      Databases such as MEDLINE, PsychINFO, PubMed, MedLine, and Cochrane Reviews were
      searched. The searches were inclusive of studies published in English between
      1966 and October 2013. Raters conducted full-text review of the resulting
      articles for the following eligibility criteria: (1) participants were 18 years
      or older, (2) the majority of patients in the sample were diagnosed with a
      gastrointestinal cancer, (3) the trial was testing a psychosocial intervention,
      and (4) random assignment to one or more interventions versus a usual care,
      placebo, attention control, or waiting-list control condition. RESULTS: The
      interventions that were eligible for this review included psychosocial or
      behavioral intervention (e.g., cognitive behavioral therapy, problem solving,
      educational, and collaborative care), physical activity, and/or
      psychopharmacologic treatment (e.g., selective serotonin reuptake inhibitor).
      Interventions that included dietary changes were not included in the present
      review. Study quality was also assessed using the Physiotherapy Evidence Database
      (PEDro) system. The results of the review resulted in a finding of eight studies
      to have been conducted, testing psychosocial interventions, in patients with
      gastrointestinal cancers. Findings of these studies suggested that the
      interventions were effective in reducing psychological and physical symptoms
      associated with the cancer, improved quality of life, and reduced immune system
      dysregulation, and one study demonstrated an improvement in survival. Two studies
      reported no benefit from psychosocial intervention when compared with a control
      group. The quality of the studies varied greatly, but reporting of the details of
      the trials, and the methodological rigor, improved over time. CONCLUSION: Further
      research is warranted to design and test interventions that may be effective in
      patients diagnosed with gastrointestinal cancers.

PMID- 24733569
TI  - The role of HBsAg levels in the current management of chronic HBV infection.
AB  - Chronic hepatitis B virus (HBV) infection can result in liver cirrhosis, hepatic
      decompensation, and hepatocellular carcinoma (HCC). However, the natural course
      of the disease is highly dynamic and not every patient requires therapy. The
      challenges for optimal management are who to treat, which therapeutic regimen to
      use, and when to begin or stop treatment. Constant monitoring is mandatory to
      predict the natural course and guide treatment decisions. Surrogate markers for
      baseline and on treatment decisions are needed. Besides HBV DNA, hepatitis B
      surface antigen levels also proved to be useful to help judge the natural course
      and guide treatment. High levels of HBsAg are suggestive of low fibrosis and
      immune tolerance in hepatitis B e antigen (HBeAg) positive patients; whereas low
      levels of HBsAg indicate a lower risk for HCC and inactive carrier state in HBeAg
      negative patients. Data also support the possible use of HBsAg levels as an on
      treatment response marker. So far, the best evidence exists for treatment with
      interferon (IFN)-alpha where lack of HBsAg decline after 12 weeks is associated
      with non-response. Thus, stopping rules after 12 weeks therapy could be
      established for HBeAg positive as well as for HBeAg negative patients. However,
      the positive predictive value for achieving sustained response is still vague.
      The value of HBsAg monitoring is less clear during treatment with nucleos(t)ide
      analogues (NA) but it can be a useful marker for new concepts such as stopping NA
      or add-on IFN strategies. Currently, several studies are underway to validate
      HBsAg in these settings.

PMID- 24733571
TI  - Ventricular B1 (+) perturbation at 7 T - real effect or measurement artifact?
AB  - The objective of this work was to explore the origin of local B1 (+)
      perturbations in the ventricles measured at 7 T. The B1 (+) field in the human
      brain was mapped using four different MRI techniques: dual refocusing echo
      acquisition mode (DREAM), actual flip-angle imaging (AFI), saturated double-angle
      method (SDAM) and Bloch-Siegert shift (BSS). Electromagnetic field simulations of
      B1 (+) were performed in male and female subject models to assess the dependence
      of the B1 (+) distribution on the dielectric properties of cerebrospinal fluid
      and subject anatomy. All four B1 (+) mapping techniques, based on different B1
      (+) encoding mechanisms, show 'residual' structure of the ventricles, with a
      slightly enhanced B1 (+) field in the ventricles. Electromagnetic field
      simulations indicate that this effect is real and arises from the strong contrast
      in electrical conductivity between cerebrospinal fluid and brain tissue. The
      simulated results were in good agreement with those obtained in three volunteers.
      Measured local B1 (+) perturbations in the ventricles at 7 T can be partially
      explained by the high contrast in electrical conductivity between cerebrospinal
      fluid and white matter, in addition to effects related to the particular B1 (+)
      measurement technique used.

PMID- 24733570
TI  - Closing the gap in hypertension control between younger and older adults:
      National Health and Nutrition Examination Survey (NHANES) 1988 to 2010.
AB  - BACKGROUND: Joint National Committee goal blood pressure for all adults was
      <140/<90 mm Hg or lower from 1984 to 2013. Adults aged >=60 years (older) have
      mainly isolated systolic hypertension, with major trials attaining systolic blood
      pressure <150 but not <140 mm Hg. The main objective was to assess changes in
      hypertension control to <140/<90 mm Hg in younger (aged <60 years) and older
      adults and <150/<90 mm Hg in the latter. METHODS AND RESULTS: National Health and
      Nutrition Examination Surveys (NHANES) 1988 to 1994, 1999 to 2004, and 2005 to
      2010 were analyzed in adults aged >=18 years. From 1988 to 1994 to 2005 to 2010,
      hypertension control to <140/<90 mm Hg improved in older (31.6% to 53.1%;
      P<0.001) and younger (45.7% to 55.9%; P<0.001) patients. The age gap in control
      declined from 14.1% (P<0.01) in 1988 to 1994 to 2.8% (P=0.13) in 2005 to 2010.
      Better hypertension control reflected increased percentages of older (55.6% to
      77.5%) and younger (34.6% to 54.7%) patients on treatment and treated older
      (45.7% to 64.9%) and younger (56.8% to 73.4%) patients controlled (all P<0.001).
      Control to <150/<90 mm Hg rose from 48.8% to 69.9% in older adults.
      Antihypertensive medication number and percentages on >=3 medications increased
      in both age groups but increased more in older patients (P<0.01). Blood pressure
      control was higher in both age groups with >=2 healthcare visits per year and on
      statin therapy. CONCLUSIONS: The age gap in hypertension control to <140/<90 mm
      Hg was virtually eliminated in 2005 to 2010 as clinicians intensified therapy,
      especially in older patients in whom isolated systolic hypertension predominates,
      controlling 70% to <150/<90 mm Hg. More frequent healthcare visits and the use of
      statin therapy may improve hypertension control in all adults.

PMID- 24733572
TI  - Ratiometric fluorescence sensing of sugars via a reversible disassembly and
      assembly of the peptide aggregates mediated by sugars.
AB  - An amphiphilic dipeptide (1) bearing pyrene and phenylboronic acid was
      demonstrated as a unique example of a ratiometric sensing system for sugars by
      reversibly converting the peptide aggregates into the monomer form of the complex
      with sugars in aqueous solutions.

PMID- 24733574
TI  - Good doctors are close and aloof with patients.

PMID- 24733573
TI  - Microglia: dismantling and rebuilding circuits after acute neurological injury.
AB  - The brain is comprised of neurons and its support system including astrocytes,
      glial cells and microglia, thereby forming neurovascular units. Neurons require
      support from glial cells to establish and maintain functional circuits, but
      microglia are often overlooked. Microglia function as the immune cell of the
      central nervous system, acting to monitor the microenvironment for changes in
      signaling, pathogens and injury. More recently, other functional roles for
      microglia within the healthy brain have been identified, including regulating
      synapse formation, elimination and function. This review aims to highlight and
      discuss these alternate microglial roles in the healthy and in contrast, diseased
      brain with a focus on two acute neurological diseases, traumatic brain injury and
      epilepsy. In these conditions, microglial roles in synaptic stripping and
      stabilization as part of neuronal:glial interactions may position them as
      mediators of the transition between injury-induced circuit dismantling and
      subsequent reorganization. Increased understanding of microglia roles could
      identify therapeutic targets to mitigate the consequences of neurological
      disease. 

PMID- 24733575
TI  - The clinical utility of fMRI for identifying covert awareness in the vegetative
      state: a comparison of sensitivity between 3T and 1.5T.
AB  - In the last few years, mental imagery fMRI paradigms have been used successfully
      to identify covert command-following and awareness in some patients who are
      thought to be entirely vegetative. However, to date there is only evidence
      supporting their use at magnetic fields of 3T, which limits their applicability
      in clinical settings where lower field strengths are typically used. Here, we
      test the 'gold standard' fMRI paradigm for detecting residual awareness in non
      responsive patients by comparing its sensitivity at 1.5T and 3T in the same group
      of healthy volunteers. We were able to successfully detect brain activity showing
      command-following in most participants at both 3T and 1.5T, with similar
      reliability. These results demonstrate that fMRI assessment of covert awareness
      is clinically viable and therefore justify a broader use of these methods in
      standard assessments in severely brain injured patients. 

PMID- 24733576
TI  - Colloidal nickel/gallium nanoalloys obtained from organometallic precursors in
      conventional organic solvents and in ionic liquids: noble-metal-free alkyne
      semihydrogenation catalysts.
AB  - Efforts to replace noble-metal catalysts by low-cost alternatives are of constant
      interest. The organometallic, non-aqueous wet-chemical synthesis of various
      hitherto unknown nanocrystalline Ni/Ga intermetallic materials and the use of
      NiGa for the selective semihydrogenation of alkynes to alkenes are reported.
      Thermal co-hydrogenolysis of the all-hydrocarbon precursors [Ni(COD)2] (COD = 1,5
      cyclooctadiene) and GaCp* (Cp* = pentamethylcyclopentadienyl) in high-boiling
      organic solvents mesitylene and n-decane in molar ratios of 1 : 1, 2 : 3 and 3 :
      1 yields the nano-crystalline powder materials of the over-all compositions NiGa,
      Ni2Ga3 and Ni3Ga, respectively. Microwave induced co-pyrolysis of the same
      precursors without additional hydrogen in the ionic liquid [BMIm][BF4] (BMIm = 1
      butyl-3-methyl-imidazolium) selectively yields the intermetallic phases NiGa and
      Ni3Ga from the respective 1 : 1 and 3 : 1 molar ratios of the precursors. The
      obtained materials are characterized by transmission electron microscopy (TEM),
      energy dispersive X-ray spectroscopy (EDX), IR, powder X-ray diffraction (PXRD)
      and atomic absorption spectroscopy (AAS). The single-source precursor
      [Ni(GaCp*)(PMe3)3] with a fixed Ni : Ga stoichiometry of 1 : 1 was employed as
      well. In comparison with the co-hydrogenolytic dual precursor source approach it
      turned out to be less practical due to inefficient nickel incorporation caused by
      the parasitic formation of stable [Ni(PMe3)4]. The use of ionic liquid
      [BMIm][BF4] as a non-conventional solvent to control the reaction and stabilize
      the nanoparticles proved to be particularly advantageous and stable colloids of
      the nanoalloys NiGa and Ni3Ga were obtained. A phase-selective Ni/Ga colloid
      synthesis in conventional solvents and in the presence of surfactants such as
      hexadecylamine (HDA) was not feasible due to the undesired reactivity of HDA with
      GaCp* leading to inefficient gallium incorporation. Recyclable NiGa nanoparticles
      selectively semihydrogenate 1-octyne and diphenylacetylene (tolan) to 1-octene
      and diphenylethylene, respectively, with a yield of about 90% and selectivities
      of up to 94 and 87%. Ni-NPs yield alkanes with a selectivity of 97 or 78%,
      respectively, under the same conditions. 

PMID- 24733577
TI  - MiR-124 inhibits myogenic differentiation of mesenchymal stem cells via targeting
      Dlx5.
AB  - MicroRNAs (miRNAs), including miR-1, miR-133, and miR-206, play a crucial role in
      muscle development by regulating muscle cell proliferation and differentiation.
      The aim of the present study was to define the effect of miR-124 on myogenic
      differentiation of mesenchymal stem cells (MSCs). The expression level of miR-124
      in skeletal muscles was much lower than those in primary cultured bone marrow
      derived MSCs and the bone, fat and brain tissues obtained from C57BL/6 mice.
      Myogenic stimuli significantly decreased the expression levels of miR-124 in
      mouse bone marrow-derived MSCs and C2C12 cells. Forced expression of miR-124
      suppressed the expression of myogenic marker genes such as Myf5, Myod1, myogenin
      and myosin heavy chain and multinucleated myotube formation. Blockade of
      endogenous miR-124 with a hairpin inhibitor enhanced myogenic marker gene
      expression and myotube formation. During myogenic differentiation of MSCs and
      C2C12 cells, the levels of Dlx5, a known target of miR-124, were inversely
      regulated with those of miR-124. Furthermore, overexpression of Dlx5 increased
      myogenic differentiation, whereas knockdown of Dlx5 using siRNA inhibited
      myogenesis in C2C12 cells. These results suggest that miR-124 is a negative
      regulator of myogenic differentiation of MSCs and that upregulation of Dlx5
      accompanied with downregulation of miR-124 by myogenic stimuli is necessary for
      the proper progression of myogenic differentiation.

PMID- 24733578
TI  - Definition of minimal duplicated region encompassing the XIAP and STAG2 genes in
      the Xq25 microduplication syndrome.
AB  - Typical Xq25 duplications are large and associated with heterogeneous phenotypes.
      Recently, small duplications involving this genomic region and encompassing the
      GRIA3 and STAG2 genes have been reported. These Xq25 microduplications are
      associated with a recognizable syndrome including intellectual disability and
      distinctive facial appearance. We report on Xq25 microduplications in two
      unrelated families identified by array comparative genomic hybridization. In both
      families, the genomic imbalances segregated with the disease in male individuals,
      while the phenotypes of the heterozygous females appeared to be modulated by
      their X-inactivation pattern. These rearrangements of about 600 kb involved only
      three genes: THOC2, XIAP, and STAG2. Further characterization by FISH analyses
      showed tandem duplication in the Xq25 locus of these genes. These data refine the
      Xq25 candidate region, identifying a minimal duplicated region of about 270 kb
      encompassing the XIAP and STAG2 genes. We discuss the function of the genes in
      the rearrangements and their involvement in the pathogenesis of this disorder.

PMID- 24733579
TI  - Relationship of community integration of persons with severe mental illness and
      mental health service intensity.
AB  - OBJECTIVE: Community integration is integral to recovery for individuals with
      severe mental illness. This study explored the integration of individuals with
      severe mental illness into mental health and non-mental health communities and
      associations with mental health service intensity. METHODS: Thirty-three
      ethnically diverse participants with severe mental illness were categorized in
      high-intensity (N=18) or low-intensity (N=15) mental health service groups.
      Community integration was assessed with measures of involvement in community
      activities, social capital resources, social support, social network maps, and
      subjective integration. RESULTS: Although participants rated themselves as being
      more integrated into the mental health community, their social networks and
      social capital were primarily derived from the non-mental health community. The
      high-intensity group had a higher proportion of members from the mental health
      community in their networks and had less overall social capital resources than
      the low-intensity group. CONCLUSIONS: The findings suggest opportunities and
      possible incongruities in the experience of community integration.

PMID- 24733580
TI  - Chronic opioid use emerging after bariatric surgery.
AB  - PURPOSE: Little is known about opioid use after bariatric surgery among patients
      who did not use opioids chronically before surgery. Our purpose was to determine
      opioid use the year after bariatric surgery among patients who did not use
      opioids chronically pre-surgery and to identify pre-surgery characteristics
      associated with chronic opioid use after surgery. METHODS: This retrospective
      cohort study across nine US health systems included 10 643 patients aged 21 years
      or older who underwent bariatric surgery and who were not chronic opioid users
      pre-surgery. The main outcome was chronic opioid use the post-surgery year
      (excluding 30 post-operative days) defined as >=10 dispensings over >=90 days or
      >=120 total days' supply. RESULTS: Overall, 4.0% (n = 421) of patients became
      chronic opioid users the post-surgery year. Pre-surgery opioid total days' supply
      was strongly associated with chronic use post-surgery (1-29 days adjusted odds
      ratio [OR] 1.89 [95%CI, 1.24-2.88]; 90-119 days OR, 14.29 [95%CI, 6.94-29.42]
      compared with no days). Other factors associated with increased likelihood of
      post-surgery chronic use included pre-surgery use of non-narcotic analgesics (OR,
      2.22 [95%CI, 1.39-3.54]), antianxiety agents (OR, 1.67 [95%CI, 1.12-2.50]), and
      tobacco (OR, 1.44 [95%CI, 1.03-2.02]). Older age (OR, 0.84 [95%CI, 0.73-0.97]
      each decade) and a laparoscopic band procedure (OR, 0.42 [95%CI, 0.25-0.70] vs.
      laparoscopic bypass) were associated with decreased likelihood of chronic opioid
      use post-surgery. CONCLUSIONS: Most patients who became chronic opioid users the
      year after bariatric surgery used opioids intermittently before surgery.

PMID- 24733581
TI  - Matthew Freeman: the sharp end of rhomboids.

PMID- 24733582
TI  - A new life for an old pump: V-ATPase and neurotransmitter release.
AB  - Neurons fire by releasing neurotransmitters via fusion of synaptic vesicles with
      the plasma membrane. Fusion can be evoked by an incoming signal from a preceding
      neuron or can occur spontaneously. Synaptic vesicle fusion requires the formation
      of trans complexes between SNAREs as well as Ca(2+) ions. Wang et al. (2014. J.
      Cell Biol. http://dx.doi.org/jcb.201312109) now find that the Ca(2+)-binding
      protein Calmodulin promotes spontaneous release and SNARE complex formation via
      its interaction with the V0 sector of the V-ATPase. 

PMID- 24733583
TI  - Quality control: quality control at the plasma membrane: one mechanism does not
      fit all.
AB  - The plasma membrane quality control system of eukaryotic cells is able to
      recognize and degrade damaged cell surface proteins. Recent studies have
      identified two mechanisms involved in the recognition of unfolded transmembrane
      proteins. One system uses chaperones to detect unfolded cytoplasmic domains of
      transmembrane proteins, whereas the second mechanism relies on an internal
      quality control system of the protein, which can trigger degradation when the
      protein deviates from the folded state. Both quality control mechanisms are key
      to prevent proteotoxic effects at the cell surface and to ensure cell integrity. 

PMID- 24733584
TI  - Ca2+-Calmodulin regulates SNARE assembly and spontaneous neurotransmitter release
      via v-ATPase subunit V0a1.
AB  - Most chemical neurotransmission occurs through Ca(2+)-dependent evoked or
      spontaneous vesicle exocytosis. In both cases, Ca(2+) sensing is thought to occur
      shortly before exocytosis. In this paper, we provide evidence that the Ca(2+)
      dependence of spontaneous vesicle release may partly result from an earlier
      requirement of Ca(2+) for the assembly of soluble N-ethylmaleimide-sensitive
      fusion attachment protein receptor (SNARE) complexes. We show that the neuronal
      vacuolar-type H(+)-adenosine triphosphatase V0 subunit a1 (V100) can regulate the
      formation of SNARE complexes in a Ca(2+)-Calmodulin (CaM)-dependent manner.
      Ca(2+)-CaM regulation of V100 is not required for vesicle acidification. Specific
      disruption of the Ca(2+)-dependent regulation of V100 by CaM led to a >90% loss
      of spontaneous release but only had a mild effect on evoked release at Drosophila
      melanogaster embryo neuromuscular junctions. Our data suggest that Ca(2+)-CaM
      regulation of V100 may control SNARE complex assembly for a subset of synaptic
      vesicles that sustain spontaneous release. 

PMID- 24733585
TI  - The role of albuminuria in the follow-up of HIV-infected pediatric patients.
AB  - BACKGROUND: In HIV-infected adults, elevated albumin has been associated with
      increased inflammatory activity, HIV-related nephropathy, and type 2 diabetes.
      Data on albuminuria in HIV-infected children are very scarce, and guidelines do
      not include routine determination of urinary albumin/creatinine ratio in this
      population. METHODS: We performed a cross-sectional study in a cohort of HIV
      infected pediatric patients. Urinary protein/creatinine and albumin/creatinine
      ratios and hematuria were determined from at least three morning urine samples,
      and glomerular filtration rate (GFR) was estimated from creatinine levels.
      Persistent renal damage was defined according to the presence of at least two
      sequentially abnormal values in one of the parameters. The relationship between
      renal damage, HIV-related variables, and metabolic comorbidities (dyslipidemia,
      fat redistribution, glucose intolerance, hypertension) was investigated. RESULTS:
      Symptom-free renal damage was observed in 13 of 68 patients (19.1%) and mainly
      consisted of persistent proteinuria (17.6%); glomerular proteinuria was twice as
      prevalent as tubular proteinuria. GFR were normal in all cases. No relationship
      between renal markers and HIV-related variables or metabolic comorbidities was
      observed. CONCLUSIONS: Mild proteinuria affected approximately one fifth of
      patients in our cohort. The determination of albuminuria allowed the
      differentiation between glomerular and tubular proteinuria, although no
      relationship with metabolic comorbidities was observed.

PMID- 24733586
TI  - Henoch-Schonlein purpura nephritis.
AB  - Henoch-Schonlein purpura (HSP) is the one of most common types of systemic
      vasculitis in childhood. Glomerulonephritis (HSPN) occurs in 30-50 % of HSP
      patients, mostly in a mild form but a small percentage of patients present with
      nephrotic syndrome or renal failure. HSPN is caused by the glomerular deposition
      of immunoglobulin A1 (IgA1)-containing immune complexes in the mesangium, the
      subepithelial and the subendothelial space. Formation of the IgA1 immune complex
      is thought to be the consequence of aberrantly glycosylated IgA1 molecules
      secreted into the circulation and their subsequent recognition by IgG specific
      for galactose-deficient IgA1. Mesangial proliferation and renal damage are
      triggered by the deposited immune complexes, which likely require activation of
      the complement system. Whereas other organ manifestations of HSP are mostly
      benign and self-limiting, HSPN might lead to chronic renal disease and end stage
      renal failure, thereby justifying immunosuppressive treatment. Long-term renal
      outcome correlates to the severity of the initial clinical presentation and the
      extent of renal biopsy changes, both of which are used to decide upon a possible
      treatment. As there are no evidence-based treatment options for severe HSPN, a
      large variety of therapeutic regimens are used. Prospective randomized controlled
      treatment studies are needed, but the low incidence of severe HSPN renders such
      studies difficult. 

PMID- 24733587
TI  - Catalytic immunoglobulin gene delivery in a mouse model of Alzheimer's disease:
      prophylactic and therapeutic applications.
AB  - Accumulation of amyloid beta-peptide (Abeta) in the brain is hypothesized to be a
      causal event leading to dementia in Alzheimer's disease (AD). Abeta vaccination
      removes Abeta deposits from the brain. Abeta immunotherapy, however, may cause T
      cell- and/or Fc-receptor-mediated brain inflammation and relocate parenchymal
      Abeta deposits to blood vessels leading to cerebral hemorrhages. Because
      catalytic antibodies do not form stable immune complexes and Abeta fragments
      produced by catalytic antibodies are less likely to form aggregates, Abeta
      specific catalytic antibodies may have safer therapeutic profiles than reversibly
      binding anti-Abeta antibodies. Additionally, catalytic antibodies may remove
      Abeta more efficiently than binding antibodies because a single catalytic
      antibody can hydrolyze thousands of Abeta molecules. We previously isolated Abeta
      specific catalytic antibody, IgVL5D3, with strong Abeta-hydrolyzing activity.
      Here, we evaluated the prophylactic and therapeutic efficacy of brain-targeted
      IgVL5D3 gene delivery via recombinant adeno-associated virus serotype 9 (rAAV9)
      in an AD mouse model. One single injection of rAAV9-IgVL5D3 into the right
      ventricle of AD model mice yielded widespread, high expression of IgVL5D3 in the
      unilateral hemisphere. IgVL5D3 expression was readily detectable in the
      contralateral hemisphere but to a much lesser extent. IgVL5D3 expression was also
      confirmed in the cerebrospinal fluid. Prophylactic and therapeutic injection of
      rAAV9-IgVL5D3 reduced Abeta load in the ipsilateral hippocampus of AD model mice.
      No evidence of hemorrhages, increased vascular amyloid deposits, increased
      proinflammatory cytokines, or infiltrating T-cells in the brains was found in the
      experimental animals. AAV9-mediated anti-Abeta catalytic antibody brain delivery
      can be prophylactic and therapeutic options for AD.

PMID- 24733589
TI  - Structural modification strategies for the rational design of red/NIR region
      BODIPYs.
AB  - This review focuses on classifying different types of long wavelength absorbing
      BODIPY dyes based on the wide range of structural modification methods that have
      been adopted, and on tabulating their spectral and photophysical properties. The
      structure-property relationships are analyzed in depth with reference to
      molecular modeling calculations, so that the effectiveness of the different
      structural modification strategies for shifting the main BODIPY spectral bands to
      longer wavelengths can be readily compared, along with their effects on the
      fluorescence quantum yield (PhiF) values. This should facilitate the future
      rational design of red/NIR region BODIPY dyes for a wide range of different
      applications. 

PMID- 24733588
TI  - Clearance of amyloid-beta in Alzheimer's disease: shifting the action site from
      center to periphery.
AB  - Amyloid-beta (Abeta) is suggested to play a causal role in the pathogenesis of
      Alzheimer's disease (AD). Immunotherapies are among the most promising Abeta
      targeting therapeutic strategies for AD. But, to date, all clinical trials of
      this modality have not been successful including Abeta vaccination (AN1792), anti
      Abeta antibodies (bapineuzumab, solanezumab and ponezumab), and intravenous
      immunoglobulin (IVIG). We propose that one reason for the failures of these
      clinical trials may be the adverse effects of targeting the central clearance of
      amyloid plaques. The potential adverse effects include enhanced neurotoxicity
      related to Abeta oligomerization from plaques, neuroinflammation related to
      opsonized Abeta phagocytosis, autoimmunity related to cross-binding of antibodies
      to amyloid precursor protein (APP) on the neuron membrane, and antibody-mediated
      vascular and neuroskeletal damage. Overall, the majority of the adverse effects
      seen in clinical trials were associated with the entry of antibodies into the
      brain. Finally, we propose that peripheral Abeta clearance would be effective and
      safe for future Abeta-targeting therapies.

PMID- 24733590
TI  - Effects of a combination of losartan and hydrochlorothiazide in patients with
      hypertension and a history of heart failure.
AB  - OBJECTIVES: To evaluate the switching from an angiotensin receptor blocker (ARB)
      to a drug combination containing an ARB and a diuretic drug in terms of effects
      on hypertension, cardiac load, and cardiac function. METHODS: In a study
      conducted on 82 patients with a history of heart failure and hypertension who had
      been treated with an ARB but failed to reach the target blood pressure, ongoing
      oral ARB treatment was switched to a drug combination of losartan and
      hydrochlorothiazide (HCTZ). Using ambulatory blood pressure monitoring (ABPM),
      the variations in blood pressure and the effects on cardiac load and cardiac
      function were evaluated before and after treatment. RESULTS: Comparison of the
      ABPM findings before and after switching treatment showed significant
      improvements in mean systolic and diastolic blood pressure, improvements in
      systolic and diastolic blood pressure 1 hour before getting out of bed, and
      improvements in the plasma levels of human brain natriuretic peptide as an
      indicator of cardiac load. CONCLUSION: The drug combination of losartan and
      hydrochlorothiazide showed a stronger antihypertensive effect than that of the
      conventional ARB and improved heart function.

PMID- 24733591
TI  - Case of exogenous insulin-derived acanthosis nigricans caused by insulin
      injections.
AB  - A 73-year-old male with diabetes mellitus had been treated with insulin for six
      years. He developed a solid mass on his left lateral of the abdomen at the
      insulin injection site. A firm subcutaneous mass with dark-red erythema was
      overlaid by dark-brown keratinized plaques. On histological examination of the
      mass, keratin proliferation and epidermal papilloma were observed. There were
      four previously reported cases of acanthosis nigricans that were considered to be
      caused by continuous injections of insulin. Using immunohistochemistry, in our
      case the findings were positive in the basal epithelial and prickle cell layers
      when the patient's lesion was dyed with insulin-like growth factor (IGF)-1
      antibody. The coexistence of dermal IGF-1 receptor and acanthosis nigricans found
      in our patient has not been reported previously, to our knowledge. 

PMID- 24733592
TI  - Case of Wenckebach-type atrioventricular block caused by administration of indigo
      carmine.
AB  - We report a case of first-degree atrioventricular (A-V) block progressing to
      second-degree (Wenckebach-type) A-V block after administration of indigo carmine
      in a patient undergoing hysterectomy under general anesthesia. We believe that
      the onset of Wenckebach-type A-V block may have been induced by one or more of
      three factors: 1) preoperative first-degree A-V block, 2) the anesthetics used
      (propofol and remifentanil), and 3) administration of indigo carmine. 

PMID- 24733593
TI  - Inhibitory effects of glutamate-stimulated astrocytes on action potentials evoked
      by bradykinin in cultured dorsal root ganglion neurons.
AB  - Patch-clamp and Ca2+-imaging techniques have revealed that astrocytes have
      dynamic properties including ion channel activity and release of
      neurotransmitters, such as adenosine triphosphate (ATP) and glutamate. Here, we
      used the patch-clamp technique to determine whether ATP and glutamate is able to
      modulate the bradykinin (BK) response in neurons cultured with astrocytes in the
      mouse dorsal root ganglia (DRG) in order to clarify the role of astrocytes in
      nociceptive signal transmission. Astrocytes were identified using a fluorescent
      anti-GFAP antibody. The membrane potential of astrocytes was about -39 mV. The
      application of glutamic acid (GA) to the bath evoked the opening of two types of
      Cl- channel in the astrocyte cell membrane with a unit conductance of about 380
      pS and 35 pS in the cell-attached mode, respectively. ATP application evoked the
      opening of two types of astrocyte K+ channel with a unit conductance of about 60
      pS and 29 pS, respectively. Application of BK to the neuron evoked an action
      potential (spike). Concomitant BK application with ATP increased the frequency of
      BK-evoked neuron spikes when neurons coexisted with astrocytes. Stimulation of BK
      with GA inhibited the BK-evoked spike under similar conditions. The application
      of furosemide, a potent cotransporter (Na+-K+-2Cl-) inhibitor, prior to
      stimulation of BK with GA blocked inhibition of the spike. It is thought that
      inhibition of the spike is related to Cl- movement from astrocytes. 

PMID- 24733594
TI  - Post-vitrectomy observation of Coat's disease associated with exudative retinal
      detachment, successfully treated with long-term silicone oil tamponade.
AB  - BACKGROUND: Treating Coat's disease with exudative retinal detachment remains a
      challenge, since vitreous surgery is frequently accompanied by serious
      complications such as secondary glaucoma. CASE: A 25-year-old woman with Coat's
      disease of the right eye had cystic exudative retinal detachment along the naso
      inferior vessels at the peripheral retina, due to 5-o'clock telangiectasia. Right
      visual acuity was finger counting. This patient underwent vitrectomy
      simultaneously with cataract surgery, completed with silicone oil replacement,
      with thorough drainage of subretinal exudates through the artificial break.
      Although the complication of secondary glaucoma developed as a result of using
      silicone oil, approximately three years after the operation, this condition was
      ameliorated by removing the silicone oil. Thus, blindness was prevented in this
      patient. CONCLUSION: Long-term tamponade with silicone oil facilitates performing
      vitreous surgery in this patient suffering from Coat's disease associated from
      exudative retinal detachment.

PMID- 24733595
TI  - Mid-ventricular obstructive hypertrophic cardiomyopathy with an apical aneurysm
      caused by vasospastic angina.
AB  - Mid-ventricular obstructive hypertrophic cardiomyopathy (MVOHCM) is a rare form
      of cardiomyopathy, characterized by the presence of a pressure gradient between
      the left ventricular basal and apical chambers and is frequently associated with
      an apical aneurysm. However, the exact cause of this aneurysm remains unknown. We
      here describe a patient with MVOHCM in whom the apical aneurysm may be caused by
      vasospastic angina. 

PMID- 24733596
TI  - Measurements of intracranial pressure and compliance index using 1.5-T clinical
      MRI machine.
AB  - OBJECTIVE: To assess a newly proposed noninvasive technique for evaluating
      intracranial pressure (ICP) index and brain compliance (BC) index based on an
      inverse analysis of a brain-circulation-equivalent electrical circuit (EC) model,
      in which cerebrospinal fluid (CSF) flow and arterial flow rates measured by using
      the phase contrast method are used as currents. MATERIALS AND METHODS:
      Quantitative phase contrast flow measurements were performed by using a 1.5-T
      scanner for 25 volunteers and 23 patients with chronic increased ICP state.
      Bilateral carotid and verrtebral arteries and CSF flows were modeled by a pair of
      electrical circuits inductively coupled by a transformer. The ICP index was
      defined as the voltage of the second order circuit, while the BC index was
      calculated as the ratio between the mutual indeuctance of the transformer and the
      reactance in the second order circuit. RESULTS: The ICP index obtained by the EC
      correlated well with the pressure gradient obtained by the Navier-Stokes
      Technique (NS-PG). The combination of NS-PG and BC index by the EC appeared to be
      appropriate for characterizing the brain circulation status of the volunteers.
      CONCLUSION: This noninvasive ICP and BC index measurement technique is more
      useful for asessment of intracranial condition.

PMID- 24733597
TI  - MRI analysis of chronological changes in free-flap volume in head and neck
      reconstruction by volumetry.
AB  - OBJECTIVE: To evaluate changes in flap volumes for head and neck cancer patients
      by MRI. METHODS: MRI examinations of a total of 21 head and neck cancer patients
      (13 males and 8 females; average age, 67 years) were performed after surgery to
      monitor changes in flap volumes, including muscle and fat content, using
      volumetric analysis of T2-weighted images at 1, 3, 6, and 12 months after
      surgery. RESULTS: Fat-to-muscle ratios of all flaps at 1 month varied (muscle/fat
      ratio, 0.04-0.96). Flap volumes in all patients decreased at 12 months after
      surgery. The average final volumes of overall, muscle, and fat volumes reached
      76.9% +/- 5.2%, 37.1% +/- 3.7%, and 85.5% +/- 5.7%, respectively. The average fat
      volume slightly increased between 6 and 12 months, whereas compared with the fat
      volume, the average muscle volume significantly decreased (p<0.001). CONCLUSIONS:
      The final overall flap volume in all patients decreased to approximately 25% of
      the original volume after surgery, which primarily resulted from muscle atrophy.
      Therefore fat-rich flaps may maintain flap volumes after surgery. MRI is a useful
      method to evaluate the size and shape of flaps of the head and neck.

PMID- 24733598
TI  - Energy for myocardial Ca2+ handling per beat increases with heart rate in excised
      cross-circulated canine heart.
AB  - OBJECTIVE: Although tachycardia is well known to increase cardiac oxygen
      consumption (Vo2) per min, the relationship between Vo2 for excitation
      contraction (E-C) coupling per beat and heart rate change over its full working
      range still remains controversial. METHODS: To elucidate this relationship, we
      varied heart rate over a reasonably wide range (60-180 beat/min) and studied the
      relationship between left ventricular (LV) Emax (load-independent contractility
      index), PVA (pressure-volume area)-independent Vo2, and basal metabolic Vo2 in
      nine excised, cross-circulated canine hearts. RESULTS: PVA-independent Vo2 per
      min significantly increased linearly with increasing heart rate while Emax
      remained unchanged. Basal metabolic Vo2 per min was measured under KCl arrest. E
      C coupling Vo2 per min obtained by subtracting the constant basal metabolic Vo2
      from the PVA-independent Vo2 also significantly increased linearly with
      increasing heart rate. However, PVA-independent Vo2 per beat significantly
      decreased with increasing heart rate. In contrast, E-C coupling Vo2 per beat, as
      well as that normalized to Emax, slightly but significantly increased with
      increasing heart rate. CONCLUSION: The E-C coupling energy for myocardial Ca2+
      handling increases with heart rate despite constant contractility in the left
      ventricle of the excised cross-circulated canine heart.

PMID- 24733599
TI  - Moderate-to-high intensity aerobic exercise in patients with mild to moderate
      Alzheimer's disease: a pilot study.
AB  - OBJECTIVES: Physical exercise may modulate neuropathology and symptoms of
      Alzheimer's disease (AD). This pilot study assessed the feasibility of conducting
      a study of moderate-to-high intensity aerobic exercise in home-dwelling patients
      with mild AD. METHODS: An uncontrolled preintervention-postintervention test
      design with a single group receiving the same intervention. A total of eight
      patients with mild to moderate AD from the Copenhagen Memory clinic were included
      in the study. The intervention lasted for 14 weeks and consisted of supervised, 1
      h sessions of aerobic exercise three times per week (50-60% of heart rate reserve
      for a two-week adaptation period and 70-80 % of heart rate reserve for the
      remaining 12 weeks) Feasibility was assessed based on acceptability, including
      attendance and drop-out, safety, and patients' and caregivers' attitudes towards
      the intervention as well as other relevant parameters. RESULTS: Attendance (mean,
      range: 90 %, 70-100 %) and retention (seven out of eight) rates were very high.
      No serious adverse events were observed. In general, patients and caregivers were
      positive towards the intervention. CONCLUSION: This study shows that it is
      feasible to conduct moderate-to-high intensity aerobic exercise in community
      dwelling patients with mild AD. Our findings indicate that aspects such as a
      longer adaptation period, information about injury prevention, and need for
      involvement and support from caregivers should be addressed when planning an
      exercise intervention in an AD population.

PMID- 24733600
TI  - A new opportunity to define health care reform for children.

PMID- 24733601
TI  - C-reactive protein and bacterial infection in cirrhosis.
AB  - In the general population, C-reactive protein (CRP) level increases in the
      presence of acute or chronic inflammation and infections. In patients with
      cirrhosis, the basal level is higher than in patients without cirrhosis, due to
      chronic hepatic and other inflammation, but when infection occurs the more severe
      the underlying liver dysfunction, the lower the increase in CRP. Therefore, the
      predictive power of CRP for infection and prognosis is weak in patients with
      decompensated/advanced cirrhosis and in the intensive care setting. However,
      higher CRP and also persistently elevated CRP levels can help identify patients
      with a higher short-term risk of mortality.

PMID- 24733602
TI  - Correspondence regarding SNX8 haploinsufficiency and its potential for cardiac
      anomalies including tetralogy of Fallot.

PMID- 24733603
TI  - Evaluation of anti-oxidant and acetylcholinesterase activity and identification
      of polyphenolics of the invasive weed Dittrichia viscosa.
AB  - INTRODUCTION: The bioactive metabolites derived from weeds have attracted the
      interest of the food and pharmaceutical industries due to their health benefits.
      OBJECTIVE: To evaluate the anti-oxidant and acetylcholinesterase activity of
      Dittrichia viscosa extracts and characterise the polyphenolic metabolites using
      the LC coupled with diode-array detection (DAD) and positive mode electrospray
      ionisation (ESI) MS method with a view to evaluating the exploitation potential
      of this invasive weed. MATERIALS AND METHODS: Roots and aerial parts of D.
      viscosa were extracted with solvents of increasing polarity and their major
      polyphenolic metabolites were identified by LC - DAD/ESI(+)/MS. The total
      phenolic content of the extracts was determined using the Folin-Ciocalteu method,
      while their anti-oxidant activity was evaluated on the basis of their ability to
      scavenge the stable free radical 1,1-diphenyl-2-picrylhydrazyl (DPPH) and
      hydrogen peroxide. Thin-layer chromatography was used to screen for
      acetylcholinesterase inhibitors. RESULTS: Stem extracts gave the highest phenolic
      content, whereas the roots showed the lowest content. Twenty-five polyphenolic
      constituents of the extracts were tentatively characterised according to their MS
      and UV spectroscopic data. Among the extracts studied, roots-ethyl acetate and
      flowers-diethyl ether revealed the highest activity according to the DPPH and
      chemiluminescence assays respectively. CONCLUSION: The metabolic profile of D.
      viscosa was studied and the structures of the major polyphenolic metabolites were
      tentatively assigned based on their MS and UV-vis spectra. The extracts exhibited
      high levels of anti-oxidant and acetylcholinesterase inhibitory activity and the
      inhibitors are probably localised mainly in flowers and roots.

PMID- 24733604
TI  - Advanced glycation end products induce lipogenesis: regulation by natural
      xanthone through inhibition of ERK and NF-kappaB.
AB  - Advanced glycation end products (AGE) accumulate in diabetic patients and aged
      persons due to high amounts of 3- or 4-carbon derivatives of glucose.
      Understanding the mechanism of AGE-mediated signaling leading to these
      consequences, like oxidative stress, inflammation, apoptosis, etc. and its
      regulation would be a viable strategy to control diabetic complication and age
      related diseases. We have detected the probable mechanism by which AGE increases
      lipogenesis, the cause of fatty liver in diabetic patients. AGE increased lipid
      accumulation in different cells as shown by Oil Red O staining. AGE-mediated
      regulation of several transcription factors was determined by gel shift assay.
      Antioxidants like NAC, PDTC, and vitamin C, except mangiferin, were unable to
      protect AGE-induced activation of SREBP and subsequent lipid accumulation. AGE
      increased the phosphorylation of ERK, and IKK and also DNA binding ability of
      SREBP, thereby its dependent gene transcription. AGE induces NF-kappaB which
      might suppress PPARgamma activity, in turn reducing lipid breakdown and
      mobilization. Mangiferin not only inhibits AGE-mediated ROI generation that
      requires NF-kappaB activation, but also inhibits ERK and IKK activity, thereby
      suppression of SREBP activity and lipogenesis. Mangiferin has shown a double
      edged sword effect to suppress AGE-mediated ailments by reducing ROI-mediated
      responses as antioxidant and inhibiting SREBP activation thereby lipogenesis,
      suggesting its potential efficacy against diabetes and obesity-related diseases.

PMID- 24733605
TI  - Therapeutic monitoring of amphotericin B in Saudi ICU patients using UPLC MS/MS
      assay.
AB  - Amphotericin B (AmB) is the first-line agent for the treatment of life
      threatening invasive fungal infections. The aim of this study was to monitor AmB
      in critically ill Saudi patients in ICU after i.v. administration of 0.68 +/- 0.1
      mg/kg/day Fungizone(r). A selective, sensitive and precise UPLC MS/MS method was
      developed to measure AmB concentrations in these patients. Seven ICU patients
      with creatinine clearance (ClCr) >40 mL/min were included. AmB levels were
      analyzed using a Waters Aquity UPLC MS/MS system, a BEH Shield RP18 column and
      detection via electrospray ionization source with positive ionization mode. The
      precision and accuracy of the developed UPLC method in the concentration range of
      200-4000 ng/mL show no significant difference among inter- and-intra-day analysis
      (p > 0.05). Linearity was observed over the investigated range with correlation
      coefficient, r > 0.995 (n = 6/day). The pharmacokinetics of AmB in these
      patients, at steady state, showed a high terminal half-life of 124.6 +/- 73.4 h,
      with a highest concentration of 513.9 +/- 281.1 ng/mL, a lowest concentration
      316.4 +/- 129.0 ng/mL and a mean clearance 91.1 +/- 39.2 mL/h/kg. The
      pharmacokinetics of AmB in critically ill Saudi patients in ICU was studied using
      a fully validated assay. A weak correlation (r = -0.22) of AmB Cl with ClCr was
      obtained, which suggests the need for further investigation in a larger
      population.

PMID- 24733606
TI  - MicroRNA-122 overexpression promotes hepatic differentiation of human adipose
      tissue-derived stem cells.
AB  - MicroRNAs are the regulatory molecules in post-transcriptional regulation of gene
      expression, which affect diverse biological processes and have been found to play
      important roles in regulating stem cell character in plants and animals. The aim
      of this study was to identify the role of miR-122 during hepatic differentiation
      of human adipose tissue-derived stem cells (hADSCs), and also to investigate
      whether overexpression of miR-122 could enhance differentiation of hADSCs toward
      functional hepatocyte-like cells without any extrinsic factor. To investigate
      this, the level of miR-122 was monitored by quantitative real-time PCR (qRT-PCR)
      at specific time intervals following hepatic differentiation of hADSCs using
      growth factors. For the next step, lentiviral transduction was applied to
      overexpress miR-122 in hADSCs for up to 21 days. Hepatic functionality was
      evaluated by analyzing specific hepatocyte genes and biochemical markers at
      different time points of differentiation induction. The qRT-PCR results revealed
      that miR-122 was upregulated during hepatic differentiation of hADSCs.
      Additionally, the stable miR-122 overexpression in hADSCs resulted in increased
      expression of specific hepatocyte markers such as ALB, AFP, CK18, CK19, and HNF4a
      compared with the negative control cells. Moreover, urea and albumin production
      as well as glycogen deposits were observed in the treated cells. Therefore, our
      findings demonstrate that the hepatic differentiation process could be improved
      by the overexpression of miR-122 in hADSCs, making it a potential therapeutic
      resource for liver disorders.

PMID- 24733607
TI  - [Researcher of the Month April 2014].

PMID- 24733609
TI  - Priorities for the next Indian government's reform of healthcare.

PMID- 24733610
TI  - Using the Oaxaca-Blinder decomposition as an empirical tool to analyze racial
      disparities in obesity.
AB  - OBJECTIVE: Racial disparities in obesity in the US are often assumed to reflect
      racial disparities in socio-economic status, diet and physical-activity. We
      present an econometric method that helps examine this by "decomposing" the racial
      gap in body-mass index (BMI) into how much can be explained by racial differences
      in "standard" predictors of BMI, and how much remains unexplained. METHODS: The
      Oaxaca-Blinder decomposition is widely used in other fields, but remains under
      utilized in the obesity literature. We provide algebraic and graphical
      illustrations of the decomposition, and further illustrate it with an example
      using data for white and black respondents in Mississippi and Alabama. BMI is the
      outcome of interest. Predictor variables include income, education, age, marital
      status, children, mental health indicators, diet and exercise. RESULTS: The mean
      predicted gap in BMI between white and black men is small, statistically
      insignificant, and can be attributed to racial differences in the predictor
      variables. The mean predicted gap for women is larger, statistically significant,
      and <10% of it can be explained by differences in predictor variables.
      Implications of the findings are discussed. CONCLUSION: Wider application of this
      method is advocated in the obesity literature, to better understand racial
      disparities in obesity.

PMID- 24733611
TI  - AIE macromolecules: syntheses, structures and functionalities.
AB  - Macromolecules with aggregation-induced emission (AIE) attributes are a class of
      luminescent materials that display enhanced emission when they are aggregated.
      They have attracted much attention because of their good solubility,
      processability, high emission efficiency in the aggregated states, etc. A large
      variety of AIE macromolecules have been developed, showing exponential growth of
      research interest in this field. This review summarizes the design principles and
      recent synthetic advancements, topological structures, as well as the frontiers
      of functionalities and potential applications of AIE macromolecules, especially
      fluorescence sensing, biological applications and optoelectronic applications,
      with an emphasis on the recent progress. New luminogenic systems without
      conventional chromophores displaying aggregated state emission are discussed. The
      highly dense clusters of heteroatoms with lone pair electrons in these systems
      may serve as the chromophore and are cited as "heterodox clusters". It is
      expected that the mechanistic insights into the AIE phenomena, based on the
      restriction of intramolecular motions and structure rigidification, can guide the
      future design of AIE materials with fascinating structures and functionalities. 

PMID- 24733612
TI  - Portal hypertension complicating myelofibrosis in a patient without portal or
      hepatic vein thrombosis.

PMID- 24733613
TI  - [Multimodal management in soft tissue sarcoma of the trunk and extremities].
AB  - Soft tissue sarcoma (STS) is a rare, extremely heterogeneous group of malignant
      tumors of mesodermal origin. With an incidence of 1-5 per 100,000/year they
      account for only 1 % of all human malignancies. The STSs occur predominantly in
      the lower extremities and the trunk. To date 100 different histopathological
      subentities can be defined. The prognosis varies substantially depending on the
      localization and histology. Whereas local recurrence rates and overall survival
      of sarcomas of the extremities have benefited from the introduction of multimodal
      therapies, only marginal progress has been made in the management of trunk STSs.
      This manuscript gives an overview of preoperative diagnostics, pathology and
      neoadjuvant as well as adjuvant therapeutic options for soft tissue sarcoma. 

PMID- 24733615
TI  - Graphene nanoribbon blends with P3HT for organic electronics.
AB  - In organic field-effect transistors (OFETs) the electrical characteristics of
      polymeric semiconducting materials suffer from the presence of
      structural/morphological defects and grain boundaries as well as amorphous
      domains within the film, hindering an efficient transport of charges. To improve
      the percolation of charges we blend a regioregular poly(3-hexylthiophene) (P3HT)
      with newly designed N = 18 armchair graphene nanoribbons (GNRs). The latter,
      prepared by a bottom-up solution synthesis, are expected to form solid aggregates
      which cannot be easily interfaced with metallic electrodes, limiting charge
      injection at metal-semiconductor interfaces, and are characterized by a finite
      size, thus by grain boundaries, which negatively affect the charge transport
      within the film. Both P3HT and GNRs are soluble/dispersible in organic solvents,
      enabling the use of a single step co-deposition process. The resulting OFETs show
      a three-fold increase in the charge carrier mobilities in blend films, when
      compared to pure P3HT devices. This behavior can be ascribed to GNRs, and
      aggregates thereof, facilitating the transport of the charges within the
      conduction channel by connecting the domains of the semiconductor film. The
      electronic characteristics of the devices such as the Ion/Ioff ratio are not
      affected by the addition of GNRs at different loads. Studies of the electrical
      characteristics under illumination for potential use of our blend films as
      organic phototransistors (OPTs) reveal a tunable photoresponse. Therefore, our
      strategy offers a new method towards the enhancement of the performance of OFETs,
      and holds potential for technological applications in (opto)electronics. 

PMID- 24733614
TI  - Elevated neurofilament light chain (NFL) mRNA levels in prediabetic peripheral
      neuropathy.
AB  - Evidence suggests that peripheral nerve injury occurs during the early stages of
      disease with mild glycemic dysregulation. Two proteins, neuron-specific enolase
      (NSE) and neurofilament light chain (NFL), have been examined previously as
      possible markers of neuronal damage in the pathophysiology of neuropathies.
      Herein, we aimed to determine the potential value of circulatory NSE and NFL mRNA
      levels in prediabetic patients and in those with peripheral neuropathy. This
      prospective clinical study included 45 prediabetic patients and 30 age- and sex
      matched controls. All prediabetic patients were assessed with respect to diabetes
      related microvascular complications, such as peripheral neuropathy, retinopathy
      and nephropathy. mRNA levels of NSE and NFL were determined in the blood by real
      time polymerase chain reaction. NSE mRNA levels were similar between prediabetic
      and control groups (p > 0.05), whereas NFL mRNA levels were significantly higher
      in prediabetics than in controls (p < 0.001). NSE mRNA levels did not
      significantly differ between prediabetic patients with and without peripheral
      neuropathy (p > 0.05), while NFL mRNA levels were significantly higher in
      prediabetics with peripheral neuropathy than in those without (p = 0.038).
      According to correlation analysis, NFL mRNA levels were positively correlated
      with the Douleur Neuropathique 4 questionnaire score in prediabetic patients (r =
      0.302, p = 0.044). This is the first study to suggest blood NFL mRNA as a
      surrogate marker for early prediction of prediabetic peripheral neuropathy, while
      NSE mRNA levels may be of no diagnostic value in prediabetic patients.

PMID- 24733616
TI  - Maternal and child roles in the feeding relationship: what are mothers doing?

PMID- 24733617
TI  - Difference in differences for stayers with a time-varying qualification: health
      expenditure elasticity of the elderly.
AB  - In difference in differences, a treatment is applied only to a qualified group at
      some time point. The qualification may be time-constant as in gender, or time
      varying as in residential location. When the qualification is time-varying, there
      appear four groups: the newly qualified (in-movers), the already qualified (in
      stayers), the newly disqualified (out-movers), and the already disqualified (out
      stayers). A change in qualification may affect the response variable of interest
      even when the treatment effect is zero, which is an 'untreated moving effect'.
      Also, when the treatment effect is not zero, it may be different across the four
      groups. The conventional difference in differences fails to remove untreated
      moving effects and ignores the possible treatment effect heterogeneity across the
      groups. This paper shows how to account for untreated moving effects and proposes
      'the effect on in-stayers' as the main effect of interest. Our proposal can be
      implemented with least squares estimator for panel models or with nonparametric
      methods. An empirical analysis is provided using Korean data for the effects of
      the basic elder pension on health-care expenditure.

PMID- 24733618
TI  - Spectrum of pediatric brain tumors: a report of 341 cases from a tertiary cancer
      center in India.
AB  - Brain tumors are the second most common cancers after hematological malignancies
      accounting for approximate 21% of all childhood malignancies in children between
      ages of 0 and 14 y. The present study was undertaken to determine the spectrum of
      the brain tumors diagnosed in a tertiary cancer center in South India. A
      retrospective analysis of the data of pediatric brain tumors diagnosed between
      2003 and 2009 was done and data was classified according to the age, gender and
      histology types. Out of 2,844 pediatric patients, 341 (11.99%) were diagnosed as
      having brain tumors. Most of the patients were in the age group of >5-14 y. Male
      to female ratio was 1.58:1. The most common pediatric brain tumor was
      medulloblastoma followed by astrocytoma and ependymoma. Glioblastoma multiforme
      was the most common subtype of astrocytoma. Other common tumors were glioma,
      oligodendroglioma, periphereral neuroectodermal tumor and germ cell tumor. As
      compared to western data, incidence of brain tumors in children was found to be
      less in the present study.

PMID- 24733619
TI  - Mean platelet volume and uric acid levels in neonatal sepsis.
AB  - OBJECTIVES: To determine the role of mean platelet volume (MPV) and uric acid
      levels in the diagnosis of neonatal sepsis (NS). METHODS: A total of 146 newborns
      with suspected NS were prospectively included in the study and infants without NS
      (n = 142) were assigned as controls. The patients were divided into three groups:
      Group I (n = 64): clinical NS, Group II (n = 82): culture-proven NS, and Group
      III (n = 142): healthy controls. RESULTS: The patients in Group II had the
      highest C-reactive protein (CRP) levels (54.6 +/- 5.4 mg/L), lowest platelet
      counts (199,329 +/- 135,952/mm(3)) and lowest uric acid levels (2.6 +/- 1.8
      mg/dL) when compared to Groups I and III (p < 0.05, for all comparisons). MPV
      values were higher in Group I (10.6 +/- 1.1 fL) and Group II (10.4 +/- 0.9 fL)
      when compared to Group III (9.2 +/- 1.2 fL) (p = 0.001), although there was no
      difference between Groups I and II. Area under curve (AUC) values for CRP, MPV,
      and uric acid were 0.92 (p = 0.001), 0.76 (p = 0.001) and 0.28 (p = 0.001),
      respectively. The diagnostic cut-off values for CRP and MPV were 9.5 mg/dL and
      10.4 fL. Sensitivity and specificity of MPV in NS were 54 % and 82 %
      respectively. When combined with CRP its sensitivity and specificity increased to
      89 % and 79 % respectively. CONCLUSIONS: The combined use of CRP and MPV should
      be considered in the early diagnosis of NS, but uric acid levels may only be
      utilized as an additional tool to support diagnosis. CRP is shown to be more
      sensitive and specific than MPV and uric acid in diagnosing neonatal sepsis.

PMID- 24733621
TI  - Subjective sleep characteristics associated with anxiety and depression in older
      adults: a population-based study.
AB  - OBJECTIVE: Sleep complaints are often associated with anxiety and depression, but
      the specific complaints related to each syndrome are poorly characterized,
      especially in older adults. The objective was to identify subjective sleep
      characteristics specific to anxiety and depression in this population. METHODS: A
      random sample of 2393 individuals aged 65 years or older was used. Anxiety and
      depression were categorized using DSM-V criteria for phobias, panic disorder,
      generalized anxiety disorder, unspecified anxiety disorder, major depressive
      episode, and depressive episode with insufficient symptoms. Subjective sleep
      characteristics were measured using the Pittsburgh Sleep Quality Index. Logistic
      regression models predicting anxiety or depression were used to determine the
      independent sleep characteristics associated with each syndrome adjusting for
      age, sex, education level, cognitive functioning, anxiolytic/sedative/hypnotic
      use, antidepressants use, subjective health, chronic diseases, cardiovascular
      conditions, and anxiety or depression (as appropriate). RESULTS: Nearly all
      Pittsburgh Sleep Quality Index subscales were significantly associated with
      anxiety, but these subscales shared variance and only sleep duration in hours,
      sleep disturbance score, and daytime functioning score were independently related
      to anxiety. Within these significant subscales, the main specific sleep
      complaints associated with anxiety were daytime sleepiness and sleep disturbances
      related to coughing/snoring, feeling cold, and bad dreams. The use of sleeping
      medication was the only specific sleep characteristic associated with depression.
      CONCLUSIONS: These results suggest that in older adults, symptoms of short sleep
      duration, daytime sleepiness and sleep disturbances are independently related to
      anxiety while the use of sleep medication is independently associated to
      depression.

PMID- 24733620
TI  - Multiple system atrophy and amyotrophic lateral sclerosis in a family with
      hexanucleotide repeat expansions in C9orf72.
AB  - IMPORTANCE: Here we report a family with coexistence of multiple system atrophy
      (MSA) and amyotrophic lateral sclerosis (ALS) with hexanucleotide repeat
      expansions in C9orf72. OBSERVATIONS: A 65-year-old woman had a 2-year history of
      ataxia with autonomic dysfunction but without motor neuron signs. She was
      diagnosed as having MSA based on her clinical history and the hot cross bun sign
      on brain magnetic resonance imaging. Her 62-year-old brother had progressive
      weakness, fasciculations, hyperreflexia, and active denervation on
      electromyography without cerebellar ataxia. He was diagnosed as having ALS. Both
      patients had a greater than 1000/2 hexanucleotide expansion in C9orf72.
      CONCLUSIONS AND RELEVANCE: Patients with hexanucleotide repeat expansions in
      C9orf72 can present with MSA as well as ALS or frontotemporal dementia. We report
      this family with coexisting MSA and ALS, highlighting the phenotypic variability
      in neurologic presentations with hexanucleotide repeat expansions in C9orf72.

PMID- 24733622
TI  - Gelatin tannate for treating acute gastroenteritis: a systematic review.
AB  - Gelatin tannate (GT) is a complex of tannic acid, which possesses astringent,
      antibacterial, and anti-inflammatory properties, and a protective gelatin. It is
      increasingly being marketed as an antidiarrheal drug. Our aim was to review data
      on the effectiveness of GT in treating acute gastroenteritis (AGE) in children
      and adults. The MEDLINE, EMBASE, and the Cochrane Library databases were searched
      in July 2013, with no language restrictions, for controlled clinical trials.
      Additional references were obtained from reviewed articles. Two trials met the
      inclusion criteria. In adults, one randomized controlled trial involving 40
      subjects (mean age: 43+/-13 years) found that, compared with placebo, GT may be
      more effective at reducing some symptoms of AGE in the first 48 h after
      initiation of treatment. In children, one poor quality study (no randomization
      and no blinding) involving 211 children (mean age: 2.5+/-2.4 years) reported some
      beneficial effect of GT at 12 h after initiation of treatment. None of the
      studies evaluated the effect of GT on the primary outcome measures for this
      review such as stool output, duration of diarrhea, admission to hospital,
      duration of hospital stay, and (in children) weight gain after rehydration.
      Currently, there is no evidence to support the use of GT for treating AGE in
      children and only sparse evidence to support the use of GT in adults. Further
      well-designed trials, with sufficient power, adequate follow-up periods, and
      clinically relevant outcome measures, are needed. These include stool volume,
      duration of diarrhea, admission to hospital, duration of hospital stay, weight
      gain after rehydration, and adverse effects.

PMID- 24733627
TI  - Assessing accuracy on the front lines: a pragmatic approach for single-donor
      proficiency testing.

PMID- 24733628
TI  - Analysis of parabens in dentifrices and the oral cavity.
AB  - This study analyzed levels of parabens in commercial dentifrices and saliva. HPLC
      was performed using 35% acetonitrile and measuring absorbance at 254 nm. Thirteen
      toothpastes and five mouthwashes were analyzed. Of these, volunteers used three
      toothpastes and two mouthwashes, and levels of parabens were analyzed in saliva
      and water used for mouth rinsing. In toothpastes, the highest concentrations of
      methylparaben (MP), propylparaben (PP) and n-butylparaben (nBP) were 1.86, 1.42
      and 1.87 mg/g, respectively. In mouthwashes, the highest concentrations of MP and
      PP were 0.97 and 0.11 mg/mL, respectively. After volunteers used 500 mg
      toothpaste T-1, which contained 895 ug MP, the first and tenth mouth rinse
      samples contained means of 64.63 and 1.89 ug MP, respectively. After rinsing the
      mouth three or five times, 37 ug or 18 ug MP was calculated to remain in the oral
      cavity, respectively. After using 20 mL mouthwash S-1, which contained 19 mg MP,
      1.53 mg MP was calculated to remain in the oral cavity. Immediately after using
      this mouthwash, the mean salivary concentration of MP was 237 ug/mL. The daily
      intake of parabens from dentifrices was predicted to be insignificant compared
      with the intake from food; however, parabens can be ingested from dentifrices.

PMID- 24733629
TI  - Isoforms of receptors of fibroblast growth factors.
AB  - The breadth and scope of Fibroblast Growth Factor signaling is immense, with
      documentation of its role in almost every organism and system studied so far. FGF
      ligands signal through a family of four distinct tyrosine kinase receptors, the
      FGF receptors (FGFRs). One contribution to the diversity of function and
      signaling of FGFs and their receptors arises from the numerous alternative
      splicing variants that have been documented in the FGFR literature. The present
      review discusses the types and roles of alternatively spliced variants of the
      FGFR family members and the significant impact of alternative splicing on the
      physiological functions of five broad classes of FGFR isoforms. Some
      characterized known regulatory mechanisms of alternative splicing and future
      directions in studies of FGFR alternative splicing are also discussed. Presence,
      absence, and/or the combination of specific exons within each FGFR protein impart
      upon each individual isoform its unique function and expression pattern during
      normal function and in diseased states (e.g., in cancers and birth defects). A
      better understanding of the diversity of FGF signaling in different developmental
      contexts and diseased states can be achieved through increased knowledge of the
      presence of specific FGFR isoforms and their impact on downstream signaling and
      functions. Modern high-throughput techniques afford an opportunity to explore the
      distribution and function of isoforms of FGFR during development and in diseases.

PMID- 24733630
TI  - Piper betle leaves: profiling phenolic compounds by HPLC/DAD-ESI/MS(n) and anti
      cholinesterase activity.
AB  - INTRODUCTION: Piper betle L. is a widely distributed plant in the tropical and
      subtropical regions, its leaves being largely consumed as a masticator and mouth
      freshener. OBJECTIVE: The purposes of this work were to characterise the phenolic
      profile of this species and to improve knowledge of its anti-cholinesterase
      properties. METHODS: The phenolic composition of P. betle leaf aqueous and
      ethanol extracts was characterised by HPLC coupled with a diode-array detector
      and combined with electrospray ionisation tandem MS, and in vitro cholinesterase
      inhibitory capacity of both extracts was assessed by spectrophotometric
      microassays. The effect on neuronal cells (SH-SY5Y) viability was evaluated by 3
      (4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide reduction and lactate
      dehydrogenase leakage. RESULTS: Twelve phenolic compounds, comprising a
      phenylpropanoid, five cinnamoyl and six flavonoids derivatives were identified in
      P. betle leaves. Hydroxychavicol was the major compound in both extracts;
      however, the aqueous extract presented a greater diversity of compounds. Both
      extracts showed strong activity against both acetyl- and butyrylcholinesterase,
      which can be due, at least partially, to the phenolic composition. Furthermore,
      the aqueous extract proved to be cytotoxic to human neuroblastoma cells at
      concentrations higher than 500 ug/mL. CONCLUSION: The results suggest that the
      consumption of P. betle leaves as an infusion can have a positive impact in the
      prevention and treatment of neurodegenerative diseases. Apigenin and luteolin
      derivatives are reported for the first time in this species.

PMID- 24733631
TI  - A model to resolve organochlorine pharmacokinetics in migrating humpback whales.
AB  - Humpback whales are iconic mammals at the top of the Antarctic food chain. Their
      large reserves of lipid-rich tissues such as blubber predispose them to
      accumulation of lipophilic contaminants throughout their lifetime. Changes in the
      volume and distribution of lipids in humpback whales, particularly during
      migration, could play an important role in the pharmacokinetics of lipophilic
      contaminants such as the organochlorine pesticide hexachlorobenzene (HCB).
      Previous models have examined constant feeding and nonmigratory scenarios. In the
      present study, the authors develop a novel heuristic model to investigate HCB
      dynamics in a humpback whale and its environment by coupling an ecosystem
      nutrient-phytoplankton-zooplankton-detritus (NPZD) model, a dynamic energy budget
      (DEB) model, and a physiologically based pharmacokinetic (PBPK) model. The model
      takes into account the seasonal feeding pattern of whales, their energy
      requirements, and fluctuating contaminant burdens in the supporting plankton food
      chain. It is applied to a male whale from weaning to maturity, spanning 20
      migration and feeding cycles. The model is initialized with environmental HCB
      burdens similar to those measured in the Southern Ocean and predicts blubber HCB
      concentrations consistent with empirical concentrations observed in a southern
      hemisphere population of male, migrating humpback whales. Results show for the
      first time some important details of the relationship between energy budgets and
      organochlorine pharmacokinetics.

PMID- 24733632
TI  - Predictors of unmet need for medical care among justice-involved persons with
      mental illness.
AB  - OBJECTIVE: This cross-sectional study examined factors associated with unmet need
      for care from primary care physicians or from psychiatrists among clients
      enrolled in mental health court support programs in Toronto, Ontario. METHODS:
      The sample included adults admitted to these programs during 2009 (N=994). Both
      measures of unmet need were determined by mental health court workers at program
      intake. Predictors included client predisposing, clinical, and enabling
      variables. RESULTS: Twelve percent had unmet need for care from primary care
      physicians and 34% from psychiatrists. Both measures of unmet need were
      associated with having an unknown diagnosis, having no income source or receiving
      welfare, homelessness, and not having a case manager. Unmet need for care from
      psychiatrists was associated with symptoms of serious mental illness and current
      hospitalization. CONCLUSIONS: Obtaining care from psychiatrists appears to be a
      particular challenge for justice-involved persons with mental illness. Policies
      and practices that improve access warrant more attention.

PMID- 24733633
TI  - Automated detection of circulating tumor cells with naive Bayesian classifiers.
AB  - Personalized medicine is a modern healthcare approach where information on each
      person's unique clinical constitution is exploited to realize early disease
      intervention based on more informed medical decisions. The application of
      diagnostic tools in combination with measurement evaluation that can be performed
      in a reliable and automated fashion plays a key role in this context. As the
      progression of various cancer diseases and the effectiveness of their treatments
      are related to a varying number of tumor cells that circulate in blood, the
      determination of their extremely low numbers by liquid biopsy is a decisive
      prognostic marker. To detect and enumerate circulating tumor cells (CTCs) in a
      reliable and automated fashion, we apply methods from machine learning using a
      naive Bayesian classifier (NBC) based on a probabilistic generative mixture
      model. Cells are collected with a functionalized medical wire and are stained for
      fluorescence microscopy so that their color signature can be used for
      classification through the construction of Red-Green-Blue (RGB) color histograms.
      Exploiting the information on the fluorescence signature of CTCs by the NBC does
      not only allow going beyond previous approaches but also provides a method of
      unsupervised learning that is required for unlabeled training data. A
      quantitative comparison with a state-of-the-art support vector machine, which
      requires labeled data, demonstrates the competitiveness of the NBC method.

PMID- 24733634
TI  - Sleep, fatigue, depression, and circadian activity rhythms in women with breast
      cancer before and after treatment: a 1-year longitudinal study.
AB  - PURPOSE: Sleep disturbance, fatigue and depression are common complaints in
      patients with cancer, and often contribute to worse quality of life (QoL).
      Circadian activity rhythms (CARs) are often disrupted in cancer patients. These
      symptoms worsen during treatment, but less is known about their long-term
      trajectory. METHODS: Sixty-eight women with stage I-III breast cancer (BC)
      scheduled to receive >=4 cycles of chemotherapy, and age-, ethnicity-, and
      education-matched normal, cancer-free controls (NC) participated. Sleep was
      measured with actigraphy (nocturnal total sleep time [nocturnal TST] and daytime
      total nap time [NAPTIME]) and with the Pittsburgh Sleep Quality Index (PSQI);
      fatigue with the Multidimensional Fatigue Symptom Inventory-Short Form (MFSI-SF);
      depression with the Center of Epidemiological Studies-Depression (CES-D). CARs
      were derived from actigraphy. Several measures of QoL were administered. Data
      were collected at three time points: before (baseline), end of cycle 4 (cycle 4),
      and 1 year post-chemotherapy (1 year). RESULTS: Compared to NC, BC had longer
      NAPTIME, worse sleep quality, more fatigue, more depressive symptoms, more
      disrupted CARs, and worse QoL at baseline (all p values <0.05). At cycle 4, BC
      showed worse sleep, increased fatigue, more depressive symptoms, and more
      disrupted CARs compared to their own baseline levels and to NC (all p values
      <0.05). By 1 year, BC's fatigue, depressive symptoms, and QoL returned to
      baseline levels but were still worse than those of NC, while NAPTIME and CARs did
      not differ from NC's. CONCLUSION: Additional research is needed to determine if
      beginning treatment of these symptoms before the start of chemotherapy will
      minimize symptom severity over time.

PMID- 24733636
TI  - [Coagulation medicine : Brushing up on knowledge for daily practice].

PMID- 24733635
TI  - Holistic needs assessment in advanced, intensively treated multiple myeloma
      patients.
AB  - PURPOSE: It is recommended that patients with multiple myeloma should be assessed
      for unmet holistic needs at key times in their disease trajectory. The aim of
      this exploratory study was to characterise the holistic needs of advanced,
      intensively treated multiple myeloma using a structured assessment tool. METHODS:
      Patients with multiple myeloma who had undergone a haematopoietic stem cell
      transplantation and subsequent treatment for at least one episode of progressive
      disease but were in stable plateau phase were included in the study. Patients'
      holistic needs were assessed using the self-reporting tool, Sheffield Profile for
      Assessment and Referral for Care (SPARC). RESULTS: Thirty-two patients with a
      median age of 60 years at assessment and a median of 5.5 years from diagnosis
      were recruited. Using the SPARC, half of the patients reported tiredness as
      'quite a bit/very much,' while one third complained that daytime somnolence and
      insomnia were 'quite a bit/very much.' Forty-four percent of patients reported
      pain. One third of patients were bothered and distressed by the side effects from
      their treatment and were worried about long-term effects of their treatment.
      Thirty-one percent of patients felt that the effect of their condition had an
      impact on their sexual life, and 40 % were worried about the effect that their
      illness was having on their family or other people. CONCLUSION: This is the first
      study to use a self-reported holistic needs assessment tool in multiple myeloma.
      A multidimensional structured questionnaire like the SPARC could provide a useful
      first step in the effective delivery of supportive and palliative care for
      patients with multiple myeloma.

PMID- 24733637
TI  - [Importance of thrombophilia screening].
AB  - Thrombophilia testing denotes a test battery for inherited or acquired features
      associated with a tendency for clot formation. Currently, it is being used in a
      frequency and to an extent which is not supported by evidence. In order to
      protect patients from unnecessary worry and stigmatization, but also for reasons
      of cost effectiveness, thrombophilia testing should be reduced to a very small
      number of medically justifiable indications which are outlined in this
      review.Those indications include the following: secondary prevention of venous
      thromboembolism in patients from a thrombophilic family, i.e., with two or more
      first degree relatives with venous thromboembolism (VTE), or patients with
      suspected antiphospholipid syndrome; women prior to oral contraception or
      planning to become pregnant if they had no prior VTE but have one or more first
      degree relatives with VTE-provided they are willing to follow the consequences of
      positive test results; women with recurrent miscarriage. The inappropriate
      indications are discussed as well.The test panel for inherited thrombophilias
      includes deficiencies of antithrombin, protein C and protein S, factor V Leiden
      and prothrombin 20210 mutation. Patients with suspicion of antiphospholipid
      syndrome have to be tested for lupus anticoagulans, anti-cardiolipin antibodies,
      and anti-beta2-glycoprotein I-antibodies. It is important to do the blood
      sampling at an appropriate point in time.

PMID- 24733638
TI  - [Mediterranean diet for primary prevention of cardiovascular diseases :
      Prevencion-con-Dieta-Mediterranea (PREDIMED) Study].

PMID- 24733639
TI  - MOFs as proton conductors--challenges and opportunities.
AB  - Proton conducting materials have garnered immense attention for their role as
      electrolytes in fuel cells. Metal Organic Frameworks (MOFs) and coordination
      polymers have recently been investigated as possible candidates for proton
      conducting applications. Their crystallinity, chemically functionalizable pores
      and options for systematic structural variation are some of the factors that
      allow for the targeted design of better proton conductors operating over a wide
      variety of temperatures and/or humidity conditions. This review will examine
      selected examples from this nascent field, and will focus on the design and
      synthesis of proton conducting MOFs, their properties and conditions under which
      they operate. 

PMID- 24733640
TI  - The oriented growth of tungsten oxide in ordered mesoporous carbon and their
      electrochemical performance.
AB  - Electrocatalysts for hydrogen oxidation and methanol oxidation are the heart of
      the proton exchange membrane fuel cell. In spite of tremendous efforts,
      developing low-cost anodic electrocatalysts with high catalytic activity and
      corrosion resistance is still a great challenge. Here, we report a nanocomposite
      consisting of oriented WO3 nanorods grown in ordered mesoporous carbon as a high
      performance functional catalyst carrier for proton exchange membrane fuel cells.
      As a result of the catalytic graphitization effect of tungsten compounds, the
      degree of graphitization and conductivity of mesoporous carbon film were improved
      even at a low temperature. Furthermore, compared with ordered mesoporous carbon,
      ordered mesoporous C-WO3 nanocomposites possess favorable hydrophilicity,
      excellent corrosion resistance and notable electrocatalytic activities. The
      unusual electrocatalytic activities arise from the ideal physical properties of
      the carrier and synergetic catalysis between Pt and WO3. 

PMID- 24733641
TI  - Support in the early years of life is crucial to reducing obesity.

PMID- 24733642
TI  - Determination of naphazoline hydrochloride in biological and pharmaceutical
      samples by a quantum dot-assisted chemiluminescence system using response-surface
      methodology.
AB  - A simple and highly sensitive chemiluminescence (CL) method is reported for the
      determination of naphazoline hydrochloride (NH). It was found that the weak CL
      from the reaction of luminol and KIO4 in an alkaline medium could be highly
      amplified by cysteine-capped cadmium telluride quantum dots (QDs) and the
      enhanced CL was effectively quenched by NH and this finding was utilized as a
      basis for the determination of NH. The QDs were synthesized in aqueous medium and
      characterized by X-ray diffraction (XRD), transmission electron microscopy (TEM),
      and UV-vis and photoluminescence spectroscopy. A possible mechanism was proposed
      for the CL system based on radical identification experiments, along with CL
      spectrum of the system. The experimental parameters were optimized by the
      reliable response surface methodology (RSM). Under the optimized experimental
      conditions, the proposed method allowed the determination of NH over the range of
      5.0 * 10(-10) -2.0 * 10(-7) mol/L (r(2) = 0.9993, n = 10). The precision (RSD%)
      of the method, obtained from five replicate determinations of 2.0 and 150 nmol/L
      NH, was found to be 1.0% and 1.3%, respectively. The method was successfully
      applied to the determination of NH in pharmaceutical formulations and human urine
      and serum samples with results corroborated with the aid of those obtained from a
      standard method.

PMID- 24733644
TI  - Editorial: pituitary tumors.

PMID- 24733643
TI  - The role of neuropathology in the management of progressive glioblastoma : a
      systematic review and evidence-based clinical practice guideline.
AB  - QUESTION: 1. What are the most important diagnostic considerations in reporting
      progressive glioblastoma? TARGET POPULATION: These recommendations apply to
      adults with progressive glioblastoma RECOMMENDATIONS:  LEVEL III: For patients
      who undergo biopsy or neurosurgical resection at the time of radiologic or
      clinical progression, it is recommended that the pathologist report the presence
      and extent of progressive neoplasm as well as the presence and extent of necrosis
      within the pathologic material examined. Furthermore, to ensure the proper
      interpretation of progressive glioblastoma, it is recommended that the
      pathologist take into account the patient's previous diagnosis and treatment, as
      well as the current clinical and neuroimaging features that have led to a second
      biopsy or resection. QUESTION: 2. What techniques and ancillary studies are most
      useful in separating malignant progression from treatment effect? TARGET
      POPULATION: These recommendations apply to adults with progressive glioblastoma
      RECOMMENDATIONS:  LEVEL III: In the setting of prior radiation and chemotherapy,
      it is recommended to adhere to strict histologic criteria for microvascular
      proliferation and necrosis in order to establish a diagnosis of a glioblastoma.
      Immunohistochemistry and genetic studies are selectively recommended for
      distinguishing neoplastic cells from atypical reactive cells in progressive
      glioblastoma.

PMID- 24733645
TI  - Role of child weight status and the relative reinforcing value of food in
      children's response to portion size increases.
AB  - OBJECTIVE: Food portion size is an important determinant of intake in children.
      It remains unknown if children's weight status and relative reinforcing value of
      food (RRVF) interact with portion size to affect intake. METHODS: In a randomized
      crossover design, 25 normal-weight and 25 obese children, ages 8-10 years,
      consumed dinner once a week for 3 weeks. At each dinner, the same meal was
      served, but the portion size of all foods (chicken nuggets, hash browns, ketchup,
      green beans, brownies) and a sugar-sweetened beverage (fruit punch) varied across
      conditions (100, 150, and 200%). Children's RRVF was assessed using a behavioral
      choice task. RESULTS: There was a significant main effect of portion size
      condition (P = 0.003) and weight status (P = 0.0005) and a nonsignificant trend
      for a portion size-by-weight status interaction (P = 0.108) on intake. Mean
      intakes across conditions (100, 150, and 200%) were 801 +/- 57, 964 +/- 58, and
      873 +/- 57 kcal for normal-weight children and 1041 +/- 57, 1129 +/- 57, and 1210
      +/- 57 kcal for obese children, respectively. Neither the main effect of RRVF
      status nor the condition-by-RRVF status interaction was significant (P > 0.48).
      CONCLUSIONS: Environments that offer large portions of palatable foods affect all
      children's intake irrespective of their weight status or how reinforcing they
      find food to be.

PMID- 24733647
TI  - Walled-off pancreatic necrosis: where are we?

PMID- 24733648
TI  - The effects of a physiotherapy programme on patients with a pleural effusion: a
      randomized controlled trial.
AB  - OBJECTIVE: To investigate the effects of a physiotherapy protocol on patients
      with pleural effusion. DESIGN: Randomized controlled trial. SETTING: University
      hospital. PARTICIPANTS: A total of 104 consecutive inpatients with a medical
      diagnosis of pleural effusion. INTERVENTION: Patients were randomly allocated to
      a control group receiving standard treatment (medical treatment and drainage) or
      an intervention group treated with physiotherapy added to standard treatment. The
      physiotherapy programme included deep breathing exercises, mobilizations and
      incentive spirometry. MAIN OUTCOME MEASURES: Spirometric predicted values and
      chest radiographs were measured before treatment and at discharge and the length
      of hospital stay was recorded. Assessors were blinded to the intervention.
      RESULTS: A comparative analysis showed a significant improvement of spirometric
      parameters in the intervention group; pre-to-post hospitalization predicted
      values showed significant changes in vital capacity (73.1 +/- 12.6% to 72.13 +/-
      13.7 %, P<0.001 ), forced expiratory volume in first second (72.13 +/- 13.7% to
      78.98 +/- 16.9%, P<0.001) and forced expiratory flow at 25-75 % (64.8 +/- 35.1%
      to 76.78 +/- 35.3%, P=0.198) compared to the control group that showed no
      significant changes across treatment. The radiographic findings showed better
      scores on the affected side of the thorax at discharge in the physiotherapy
      group. Length of hospital stay was also significantly (P=0.014) shorter in the
      intervention group (26.7 +/- 8.8 days) compared to the control group (38.6 +/-
      10.7 days). CONCLUSIONS: A physiotherapy programme added to standard treatment
      improves the spirometric parameters and the radiological findings and reduces the
      hospital stay in patients with a pleural effusion.

PMID- 24733646
TI  - Antecedents of intact cognition and dementia at age 90 years: a prospective
      study.
AB  - OBJECTIVES: This study aimed to examine the possible antecedents of both dementia
      and sustained intact cognition at age 90 years among men who underwent a
      prospective, multidisciplinary assessment from ages 19 to 90 years, with little
      attrition. METHODS: We conducted a prospective 20-year reassessment of 196 (out
      of 268) former Harvard college sophomores who survived until age 70 years. Since
      1939, the study gathered measurements of childhood environment, dominant
      personality traits, objective mental and physical health over time, smoking in
      pack-years, alcohol abuse, and depression. Questionnaires were obtained every 2
      years and physical exams every 5 years. Cognitive status was assessed at ages 80,
      85, and 90 years. RESULTS: Despite addressing a wide variety of health,
      behavioral, and social factors over the lifespan, we observed few predictors with
      strong association with either intact cognition at age 90 years (n = 40) or
      dementia (n = 44). Univariate analysis revealed seven suggestive predictors of
      intact cognition at age 90 years or of dementia: warm childhood relationship with
      mother, exercise at age 60 years, high maternal education, young age of mother at
      subject's birth, low body mass index, good physical health at 60 years, and late
      retirement. Only the first three variables, warm childhood relationship with
      mother, exercise at age 60 years, and high maternal education, remained
      significant with logistic regression. CONCLUSIONS: In this prospective study of
      long-lived, highly educated men, several well-known putative predictors of
      Alzheimer's disease did not distinguish those who over the next 20 years
      developed dementia from those with unimpaired cognition until age 90 years.

PMID- 24733649
TI  - Alzheimer's disease: from molecule to clinic.

PMID- 24733650
TI  - Uric formaldehyde levels are negatively correlated with cognitive abilities in
      healthy older adults.
AB  - Recent studies have shown that the abnormal accumulation of endogenous
      formaldehyde could be a critical factor in age-related cognitive decline. The aim
      of this study was to estimate the correlation between uric formaldehyde and
      general cognitive abilities in a community-based elderly population, and to
      measure the extent and direction in which the correlation varied with demographic
      characteristics. Using a double-blind design, formaldehyde in human urine was
      analyzed by high-performance liquid chromatography (n = 604), and general
      cognitive abilities were measured using the Montreal Cognitive Assessment (MoCA).
      Demographic characteristics, in terms of age, gender, residential region, and
      education were taken into consideration. We found that uric formaldehyde levels
      were inversely correlated with the MoCA score, and the concentration varied with
      demographic features: higher odds of a high formaldehyde level occurred among the
      less educated and those living in old urban or rural areas. In cytological
      experiments, the level of cellular formaldehyde released into the medium
      increased as SH-SY5Y and BV2 cells were incubated for three days. Formaldehyde in
      excess impaired the processes of N2a cells and neurites of primary cultured rat
      hippocampal cells. However, removal of formaldehyde markedly rescued and
      regenerated the processes of N2a cells. These results demonstrated a negative
      correlation between the endogenous formaldehyde and general cognitive abilities.
      High formaldehyde levels could be a risk factor for cognitive impairment in older
      adults, and could be developed as a non-invasive marker for detection and
      monitoring of age-related cognitive impairment.

PMID- 24733651
TI  - Intraneuronal accumulation of Abeta42 induces age-dependent slowing of neuronal
      transmission in Drosophila.
AB  - Beta amyloid (Abeta42)-induced dysfunction and loss of synapses are believed to
      be major underlying mechanisms for the progressive loss of learning and memory
      abilities in Alzheimer's disease (AD). The vast majority of investigations on AD
      related synaptic impairment focus on synaptic plasticity, especially the decline
      of long-term potentiation of synaptic transmission caused by extracellular
      Abeta42. Changes in other aspects of synaptic and neuronal functions are less
      studied or undiscovered. Here, we report that intraneuronal accumulation of
      Abeta42 induced an age-dependent slowing of neuronal transmission along pathways
      involving multiple synapses.

PMID- 24733652
TI  - Disrupted structural and functional brain connectomes in mild cognitive
      impairment and Alzheimer's disease.
AB  - Alzheimer's disease (AD) is the most common type of dementia, comprising an
      estimated 60-80% of all dementia cases. It is clinically characterized by
      impairments of memory and other cognitive functions. Previous studies have
      demonstrated that these impairments are associated with abnormal structural and
      functional connections among brain regions, leading to a disconnection concept of
      AD. With the advent of a combination of non-invasive neuroimaging (structural
      magnetic resonance imaging (MRI), diffusion MRI, and functional MRI) and
      neurophysiological techniques (electroencephalography and magnetoencephalography)
      with graph theoretical analysis, recent studies have shown that patients with AD
      and mild cognitive impairment (MCI), the prodromal stage of AD, exhibit disrupted
      topological organization in large-scale brain networks (i.e., connectomics) and
      that this disruption is significantly correlated with the decline of cognitive
      functions. In this review, we summarize the recent progress of brain connectomics
      in AD and MCI, focusing on the changes in the topological organization of large
      scale structural and functional brain networks using graph theoretical
      approaches. Based on the two different perspectives of information segregation
      and integration, the literature reviewed here suggests that AD and MCI are
      associated with disrupted segregation and integration in brain networks. Thus,
      these connectomics studies open up a new window for understanding the
      pathophysiological mechanisms of AD and demonstrate the potential to uncover
      imaging biomarkers for clinical diagnosis and treatment evaluation for this
      disease.

PMID- 24733653
TI  - Cerebrospinal fluid biomarkers of Alzheimer's disease.
AB  - Alzheimer's disease (AD) is a fatal neurodegenerative disorder that takes about a
      decade to develop, making early diagnosis possible. Clinically, the diagnosis of
      AD is complicated, costly, and inaccurate, so it is urgent to find specific
      biomarkers. Due to its multifactorial nature, a panel of biomarkers for the
      multiple pathologies of AD, such as cerebral amyloidogenesis, neuronal
      dysfunction, synapse loss, oxidative stress, and inflammation, are most promising
      for accurate diagnosis. Highly sensitive and high-throughput proteomic techniques
      can be applied to develop a panel of novel biomarkers for AD. In this review, we
      discuss the metabolism and diagnostic performance of the well-established core
      candidate cerebrospinal fluid (CSF) biomarkers (beta-amyloid, total tau, and
      hyperphosphorylated tau). Meanwhile, novel promising CSF biomarkers, especially
      those identified by proteomics, updated in the last five years are also
      extensively discussed. Furthermore, we provide perspectives on how biomarker
      discovery for AD is evolving.

PMID- 24733654
TI  - Neuronal failure in Alzheimer's disease: a view through the oxidative stress
      looking-glass.
AB  - Considerable debate and controversy surround the cause(s) of Alzheimer's disease
      (AD). To date, several theories have gained notoriety, however none is
      universally accepted. In this review, we provide evidence for the oxidative
      stress-induced AD cascade that posits aged mitochondria as the critical origin of
      neurodegeneration in AD.

PMID- 24733657
TI  - Understanding of BRCA1/2 genetic tests results: the importance of objective and
      subjective numeracy.
AB  - BACKGROUND: The majority of women (71%) who undergo BRCA1/2 testing-designed to
      identify genetic mutations associated with increased risk of cancer-receive
      results that are termed 'ambiguous' or 'uninformative negative'. How women
      interpret these results and the association with numerical ability was examined.
      METHODS: In this study, 477 women at increased risk for breast and ovarian cancer
      were recruited via the Cancer Genetics Network. They were presented with
      information about the four different possible BRCA1/2 test results-positive, true
      negative, ambiguous and uninformative negative-and asked to indicate which of six
      options represents the best response. Participants were then asked which
      treatment options they thought a woman receiving the results should discuss with
      her doctor. Finally, participants completed measures of objective and subjective
      numeracy. RESULTS: Almost all of the participants correctly interpreted the
      positive and negative BRCA1/2 genetic test results. However, they encountered
      difficulties interpreting the uninformative and ambiguous BRCA1/2 genetic test
      results. Participants were almost equally likely to think either that the woman
      had learned nothing from the test result or that she was as likely to develop
      cancer as the average woman. Highly numerate participants were more likely to
      correctly interpret inconclusive test results (ambiguous, OR = 1.62; 95% CI
      [1.28, 2.07]; p < 0.001; uninformative, OR = 1.40; 95% CI [1.10, 1.80]).
      DISCUSSION: Given the medical and psychological ramifications of genetic testing,
      healthcare professionals should consider devoting extra effort to ensuring proper
      comprehension of ambiguous and uninformative negative test results by women.

PMID- 24733655
TI  - Lipid metabolism in Alzheimer's disease.
AB  - Lipids play crucial roles in cell signaling and various physiological processes,
      especially in the brain. Impaired lipid metabolism in the brain has been
      implicated in neurodegenerative diseases, such as Alzheimer's disease (AD), and
      other central nervous system insults. The brain contains thousands of lipid
      species, but the complex lipid compositional diversity and the function of each
      of lipid species are currently poorly understood. This review integrates current
      knowledge about major lipid changes with the molecular mechanisms that underlie
      AD pathogenesis.

PMID- 24733656
TI  - Tau-induced neurodegeneration: mechanisms and targets.
AB  - The accumulation of hyperphosphorylated tau is a common feature of several
      dementias. Tau is one of the brain microtubule-associated proteins. Here we
      discuss tau's functions in microtubule assembly and stabilization and with regard
      to its interactions with other proteins. We describe and analyze important post
      translational modifications: hyperphosphorylation, ubiquitination, glycation,
      glycosylation, nitration, polyamination, proteolysis, acetylation, and
      methylation. We discuss how these post-translational modifications can alter
      tau's biological function. We analyze the role of mitochondrial health in
      neurodegeneration. We propose that microtubules could be a therapeutic target and
      review different approaches. Finally, we consider whether tau accumulation or its
      conformational change is related to tau-induced neurodegeneration, and propose a
      mechanism of neurodegeneration.

PMID- 24733658
TI  - DNA methylation changes in inflammatory bowel disease.
AB  - The cause of inflammatory bowel disease, encompassing Crohn's disease and
      ulcerative colitis, remains a mystery but evidence is accumulating that complex
      interactions between the genetic background and the gut microbiota of the host
      and environmental factors associated with rapid industrialization and westernized
      life styles may underlie its pathogenesis. Recent epigenetic studies have
      suggested that interactions between environment and host DNA may play a leading
      role in the phenotypical expression of both diseases, explaining amongst others
      the differences in disease expression in monozygotic twins. DNA methylation is
      the most studied epigenetic modification and during the last decade its
      correlation to IBD pathogenesis has been well established. Genes from different
      molecular pathways have been studied but till now there is no standardized
      database of methylated genes in IBD. Thus, a thorough and in depth study of DNA
      methylation, its potential relation to IBD and its interaction with the available
      pharmaceutical armamentarium is of great interest.

PMID- 24733659
TI  - Reasons for not seeking general medical care among individuals with serious
      mental illness.
AB  - OBJECTIVE: The study compared delays in seeking general medical care among adults
      with serious mental illness and a general population sample. Associations of
      delays with health status and use of emergency department services among
      individuals with serious mental illness were also assessed. METHODS: Data for 271
      persons with serious mental illness (clinic sample) and 40,016 participants in
      the National Health Interview Survey (NHIS sample) were compared. RESULTS: Fifty
      three percent of the clinic sample and 13% of the NHIS sample reported delays,
      most because of difficulties accessing services. In the clinic sample, delays
      were associated with receipt of routine care at a public clinic, rather than a
      physician's office; more severe depressive symptoms; and functional difficulties.
      Delays were also associated with poorer health status and use of emergency
      department services. CONCLUSIONS: Integration of services as envisioned in the
      Affordable Care Act and targeted case management may reduce delays among
      individuals with serious mental illness.

PMID- 24733660
TI  - Swiss cheese striatum: clinical implications.
AB  - IMPORTANCE: Markedly enlarged Virchow-Robin spaces throughout the striatum appear
      occasionally on magnetic resonance imaging (MRI) scans of the elderly, and this
      type of striatum is known as the Swiss cheese striatum (SCS); however, its
      clinical impact is unknown. OBJECTIVE: To determine the clinical features
      associated with SCS detected on MRI scans. DESIGN, SETTING, AND PARTICIPANTS: A
      blinded, retrospective case-control study using medical records from 2000 to 2007
      obtained from an MRI database at the Mayo Clinic in Rochester, Minnesota, of
      residents 40 years of age or older of Olmsted County, Minnesota, who had
      extensive Mayo Clinic medical records and MRI reports suggestive of SCS. Cases
      with a severe form of SCS (n = 27) were randomly selected for comparison with age
      , sex-, and examination year-matched controls (n = 52) with a minimal form of SCS
      or no SCS. EXPOSURE: Magnetic resonance imaging. MAIN OUTCOMES AND MEASURES:
      Associations of clinical and imaging features with the presence of a severe form
      of SCS. Medical records were reviewed for clinical features such as parkinsonism,
      dementia, and vascular risk factors. The MRI scans were visually scored for
      degree of leukoaraiosis, central atrophy, and cortical atrophy. RESULTS: No
      significant differences were found between those with a severe form of SCS and
      controls in rates of parkinsonism (19% vs 17%; odds ratio, 1.09 [95% CI, 0.28
      4.16]) or dementia of any type (30% vs 21%; odds ratio, 1.57 [95% CI, 0.48
      5.13]). Vascular risk factors were not significantly different between groups.
      Swiss cheese striatum correlated with degree of leukoaraiosis (P < .001).
      Potential associations with visualized cortical atrophy (P = .01), nonobstructive
      urinary incontinence (18.5% vs 3.9%; P = .04), and syncope (37% vs 9.6%; P = .01)
      did not hold up after correction for the false discovery rate. CONCLUSIONS AND
      RELEVANCE: Our study suggests that marked cribriform change in the striatum was
      not associated with the development of extrapyramidal clinical disorders,
      including parkinsonism. The association of SCS with leukoaraiosis suggests that
      it is part of a more generalized cerebrovascular process. Skepticism is called
      for when attributing clinical symptoms to this MRI finding.

PMID- 24733663
TI  - Identification and quantification of basophils in the airways of asthmatics
      following segmental allergen challenge.
AB  - During asthma attacks, allergens activate sensitized basophils in the lung,
      thereby aggravating symptoms. Due to the paucity of basophils in bronchial lavage
      fluid and the lack of specific basophil detection and quantification methods,
      basophil-directed research in these samples was hampered in the past. This study
      aimed to establish and validate a flow cytometry-based basophil detection and
      quantification method for human basophils from bronchoalveolar lavage (BAL) and
      blood as a prerequisite for a better understanding of their pathogenic
      contribution and subtyping of asthma phenotypes. BAL and blood leukocytes from
      seasonal asthmatics were analyzed by flow cytometry. Chipcytometry, a highly
      sensitive single-cell analysis method, was used to validate the staining panel
      for basophils. Cell differentials of May-Grunwald-Giemsa-stained cytospins were
      used to compare basophil percentages. BAL basophils are identifiable as CD123(+)
      HLA-DR(-) CD3(-) CD14(-) CD19(-) CD20(-) CD56(-) cells in flow cytometrical
      analysis. Their identity was validated by Chipcytometry. CD203c was highly
      expressed by BAL basophils, whereas it was expressed at variable levels on blood
      basophils. The two quantification methods correlated, although more basophils
      were detected by flow cytometry. Furthermore, the increase in basophil
      percentages in the lung correlated with the decrease in the basophil percentages
      in the blood after allergen challenge. We here validated a reliable basophil
      quantification method, which is independent of the cell's activation and
      degranulation state. The results obtained with this method indicate that
      basophils are directly recruited from the blood circulation to the airway lumen.

PMID- 24733664
TI  - The effects of dexpanthenol in streptozotocin-induced diabetic rats:
      histological, histochemical and immunological evidences.
AB  - This study was designed to investigate the effects of Dexpanthenol (Dxp) on liver
      and pancreas histology and cytokine levels in streptozotocine (STZ)-induced
      diabetic rats. Twenty-four Wistar albino male rats were divided into four groups:
      control, Dxp, STZ-induced diabetic (STZ) and diabetic treatment with Dexpanthenol
      (STZ-Dxp) groups. Experimental diabetes was induced by single dose STZ (50 mg/kg)
      intraperitoneally (i.p.). After administration of STZ, the STZ-Dxp group began to
      receive a 300 mg/kg/day i.p. dose of Dxp for 6 weeks. Liver and pancreas tissues
      of the control group were in normal morphology. Liver tissue of STZ group showed
      vacuolisation of hepatocytes in the liver parenchyma with enlargement of
      sinusoidal spaces and increasing amounts of connective tissue in the portal area.
      Pancreatic section of STZ group displayed beta-cells with of cytoplasmic mass,
      reduction of islet size, and atrophy. The STZ-Dxp group that received Dxp
      treatment exhibit partially normal hepatic parenchyma. Histochemical examinations
      revealed that the diabetes-induced glycogen depletion markedly improved with the
      Dxp treatment (p?0.001). The severity of degenerative alteration was lessened by
      Dxp supplementation in the STZ-Dxp group. Induction of STZ presented a
      significant increase both in interleukin-1alpha (IL-1alpha) (p=0.033) and
      monocyte chemotactic protein-1 (MCP-1) (p=0.011) levels, when compared with the
      control rats. DXP-treated diabetic rats' IL-1alpha and MCP-1 levels were similar
      to control value. This evidence suggests that Dxp is effective in reducing STZ
      induced, diabetic-related complications and may be beneficial for the treatment
      of diabetic patients.

PMID- 24733665
TI  - Optimisation of the microplate resazurin assay for screening and bioassay-guided
      fractionation of phytochemical extracts against Mycobacterium tuberculosis.
AB  - INTRODUCTION: Because of increased resistance to current drugs, there is an
      urgent need to discover new anti-mycobacterial compounds for the development of
      novel anti-tuberculosis drugs. The microplate resazurin assay (MRA) is commonly
      used to evaluate natural products and synthetic compounds for anti-mycobacterial
      activity. However, the assay can be problematic and unreliable when screening
      methanolic phytochemical extracts. OBJECTIVE: To optimise the MRA for the
      screening and bioassay-guided fractionation of phytochemical extracts using
      Mycobacterium tuberculosis H37Ra. METHODS: The effects of varying assay duration,
      resazurin solution composition, solvent (dimethyl sulphoxide - DMSO)
      concentration and type of microtitre plate used on the results and reliability of
      the MRA were investigated. The optimal bioassay protocol was applied to
      methanolic extracts of medicinal plants that have been reported to possess anti
      mycobacterial activity. RESULTS: The variables investigated were found to have
      significant effects on the results obtained with the MRA. A standardised
      procedure that can reliably quantify anti-mycobacterial activity of phytochemical
      extracts in as little as 48 h was identified. The optimised MRA uses 2% aqueous
      DMSO, with an indicator solution of 62.5 ug/mL resazurin in 5% aqueous Tween 80
      over 96 h incubation. CONCLUSION: The study has identified an optimal procedure
      for the MRA when used with M. tuberculosis H37Ra that gives rapid, reliable and
      consistent results. The assay procedure has been used successfully for the
      screening and bioassay-guided fractionation of anti-mycobacterial compounds from
      methanol extracts of Canadian medicinal plants.

PMID- 24733666
TI  - Comparing population recovery after insecticide exposure for four aquatic
      invertebrate species using models of different complexity.
AB  - Population models, in particular individual-based models (IBMs), are becoming
      increasingly important in chemical risk assessment. They can be used to assess
      recovery of spatially structured populations after chemical exposure that varies
      in time and space. The authors used an IBM coupled to a toxicokinetic
      toxicodynamic model, the threshold damage model (TDM), to assess recovery times
      for 4 aquatic organisms, after insecticide application, in a nonseasonal
      environment and in 3 spatial settings (pond, stream, and ditch). The species had
      different life histories (e.g., voltinism, reproductive capacity, mobility).
      Exposure was derived from a pesticide fate model, following standard European
      Union scenarios. The results of the IBM-TDM were compared with results from
      simpler models: one in which exposure was linked to effects by means of
      concentration-effect relationships (IBM-CE) and one in which the IBM was replaced
      by a nonspatial, logistic growth model (logistic). For the first, exposure was
      based on peak concentrations only; for the second, exposure was spatially
      averaged as well. By using comparisons between models of different complexity and
      species with different life histories, the authors obtained an understanding of
      the role spatial processes play in recovery and the conditions under which the
      full time-varying exposure needs to be considered. The logistic model, which is
      amenable to an analytic approach, provided additional insights into the
      sensitivity of recovery times to density dependence and spatial dimensions.

PMID- 24733668
TI  - Incorporation of a self-aligned selective emitter to realize highly efficient
      (12.8%) Si nanowire solar cells.
AB  - Formation of a selective emitter in crystalline silicon solar cells improves
      photovoltaic conversion efficiency by decoupling emitter regions for light
      absorption (moderately doped) and metallization (degenerately doped). However,
      use of a selective emitter in silicon nanowire (Si NW) solar cells is
      technologically challenging because of difficulties in forming robust Ohmic
      contacts that interface directly with the top-ends of nanowires. Here we describe
      a self-aligned selective emitter successfully integrated into an antireflective
      Si NW solar cell. By one-step metal-assisted chemical etching, NW arrays formed
      only at light-absorbing areas between top-metal grids while selectively retaining
      Ohmic contact regions underneath the metal grids. We observed a remarkable ~40%
      enhancement in blue responses of internal quantum efficiency, corresponding to a
      conversion efficiency of 12.8% in comparison to the 8.05% of a conventional NW
      solar cell. 

PMID- 24733667
TI  - Efficacy and tolerability of different starting doses of sorafenib in patients
      with differentiated thyroid cancer.
AB  - Sorafenib has proven efficacy in advanced differentiated thyroid cancer (DTC),
      but many patients must reduce the dose or discontinue treatment because of
      toxicity. The tolerability and efficacy of lower starting doses of sorafenib for
      DTC remain largely unstudied. Methods. We retrospectively examined overall
      survival, time to treatment failure, time to progression, discontinuation rates,
      and dose-reduction and interruption rates in patients with metastatic DTC treated
      with first-line sorafenib outside of a clinical trial. Two patient groups were
      compared; group 1 received the standard starting dose of 800 mg/day, and group 2
      received any dose lower than 800 mg/day. Results. We included 75 adult patients,
      with 51 in group 1 and 24 in group 2. Mean age at diagnosis was 54 years, and 56%
      were male. The most common histologies included 43% papillary thyroid cancer of
      the conventional type, 15% papillary thyroid cancer of the follicular variant,
      and 15% Hurthle cell carcinoma. Time to treatment failure was 10 months (95%
      confidence interval [CI]: 5.6-14.3) in group 1 and 8 months (95% CI: 3.4-12.5) in
      group 2 (p = .56). Median overall survival was 56 months (95% CI: 30.6-81.3) in
      group 1 and 30 months (95% CI: 16.1-43.8) in group 2 (p = .08). Rates of
      discontinuation due to disease progression were 79% in group 1 and 91% in group
      2, and 21% in group 1 and 9% in group 2 (p = .304) stopped treatment because of
      toxicity. Dose-reduction rates were 59% and 43% (p = .29), and interruption rates
      were 65% and 67% (p = .908) in group 1 and group 2, respectively. Conclusion.
      Efficacy and tolerability of sorafenib in treatment-naive DTC patients does not
      appear to be negatively influenced by lower starting daily doses. 

PMID- 24733669
TI  - A simple and sensitive fluorescence method for the determination of trace ozone
      in air using acridine red as a probe.
AB  - The ozone in an air sample was trapped by H3 BO3 -LK solution to produce iodine
      (I2) that interacted with excess I(-) to form I3(-). In pH 4.0 acetate buffer
      solutions, the I3(-) reacted with acridine red to form acridine red-I3 ion
      association particles that resulted in the fluorescence peak decreased at 553 nm.
      The decreased value DeltaF553 nm is linear to the O3 concentration in the range
      0.08-53.3 * 10(-6) mol/L, with a detection limit of 4 * 10(-8) mol/L. This
      fluorescence method was used to determine ozone in air samples, and the results
      were in agreement with that of indigo carmine spectrophotometry.

PMID- 24733670
TI  - Transportability of confined field trial data for environmental risk assessment
      of genetically engineered plants: a conceptual framework.
AB  - It is commonly held that confined field trials (CFTs) used to evaluate the
      potential adverse environmental impacts of a genetically engineered (GE) plant
      should be conducted in each country where cultivation is intended, even when
      relevant and potentially sufficient data are already available from studies
      conducted elsewhere. The acceptance of data generated in CFTs "out of country"
      can only be realized in practice if the agro-climatic zone where a CFT is
      conducted is demonstrably representative of the agro-climatic zones in those
      geographies to which the data will be transported. In an attempt to elaborate
      this idea, a multi-disciplinary Working Group of scientists collaborated to
      develop a conceptual framework and associated process that can be used by the
      regulated and regulatory communities to support transportability of CFT data for
      environmental risk assessment (ERA). As proposed here, application of the
      conceptual framework provides a scientifically defensible process for evaluating
      if existing CFT data from remote sites are relevant and/or sufficient for local
      ERAs. Additionally, it promotes a strategic approach to identifying CFT site
      locations so that field data will be transportable from one regulatory
      jurisdiction to another. Application of the framework and process should be
      particularly beneficial to public sector product developers and small enterprises
      that develop innovative GE events but cannot afford to replicate redundant CFTs,
      and to regulatory authorities seeking to improve the deployment of limited
      institutional resources. 

PMID- 24733671
TI  - SMART designs in cancer research: Past, present, and future.
AB  - BACKGROUND: Cancer affects millions of people worldwide each year. Patients
      require sequences of treatment based on their response to previous treatments to
      combat cancer and fight metastases. Physicians provide treatment based on
      clinical characteristics, changing over time. Guidelines for these individualized
      sequences of treatments are known as dynamic treatment regimens (DTRs) where the
      initial treatment and subsequent modifications depend on the response to previous
      treatments, disease progression, and other patient characteristics or behaviors.
      To provide evidence-based DTRs, the Sequential Multiple Assignment Randomized
      Trial (SMART) has emerged over the past few decades. PURPOSE: To examine and
      learn from past SMARTs investigating cancer treatment options, to discuss
      potential limitations preventing the widespread use of SMARTs in cancer research,
      and to describe courses of action to increase the implementation of SMARTs and
      collaboration between statisticians and clinicians. CONCLUSION: There have been
      SMARTs investigating treatment questions in areas of cancer, but the novelty and
      perceived complexity has limited its use. By building bridges between
      statisticians and clinicians, clarifying research objectives, and furthering
      methods work, there should be an increase in SMARTs addressing relevant cancer
      treatment questions. Within any area of cancer, SMARTs develop DTRs that can
      guide treatment decisions over the disease history and improve patient outcomes.

PMID- 24733672
TI  - Anti-inflammatory effects of methyl ursolate obtained from a chemically derived
      crude extract of apple peels: potential use in rheumatoid arthritis.
AB  - Ursolic acid (UA), a pentacyclic triterpene acid found in apple peels (Malus
      domestica, Borkh, Rosaceae), has a large spectrum of pharmacological effects.
      However, the vegetal matrix usually produces highly viscous and poorly soluble
      extracts that hamper the isolation of this compound. To overcome this problem,
      the crude EtOH-AcOEt extract of commercial apple peels was exhaustively treated
      with diazomethane, after which methyl ursolate (MU) was purified by column
      chromatography and characterized spectrometrically. The anti-inflammatory effects
      of UA and MU (50 mg/kg) were analyzed by zymosan-induced paw edema, pleurisy and
      in an experimental arthritis model. After 4 h of treatment with UA and MU, paw
      edema was reduced by 46 and 44 %, respectively. Both UA and MU inhibited protein
      extravasation into the thoracic cavity; tibio-femoral edema by 40 and 48 %,
      respectively; and leukocyte influx into the synovial cavity after 6 h by 52 and
      73 %, respectively. Additionally, both UA and MU decreased the levels of
      mediators related to synovial inflammation, such as KC/CXCL-1 levels by 95 and 90
      %, TNF-alpha levels by 76 and 71 %, and IL-1beta levels by 57 and 53 %,
      respectively. Both the compounds were equally effective when assayed in different
      inflammatory models, including experimental arthritis. Hence, MU may be
      considered to be a useful anti-inflammatory derivative to overcome the inherent
      poor solubility of UA for formulating pharmaceutical products.

PMID- 24733673
TI  - Suppressive effects of coixol, glyceryl trilinoleate and natural products derived
      from Coix Lachryma-Jobi var. ma-yuen on gene expression, production and secretion
      of airway MUC5AC mucin.
AB  - In this study, we investigated whether natural products including coixol derived
      from Coix Lachryma-Jobi var. ma-yuen affect MUC5AC mucin gene expression,
      production and secretion from airway epithelial cells. Confluent NCI-H292 cells
      were pretreated with oleic acid, linoleic acid, glyceryl trilinoleate, beta
      stigmasterol or coixol for 30 min and then stimulated with PMA (phorbol 12
      myristate 13-acetate), EGF (epidermal growth factor) or TNF-alpha (tumor necrosis
      factor-alpha) for 24 h. The MUC5AC mucin gene expression, mucin protein
      production and secretion were measured by RT-PCR and ELISA. The results were as
      follows: (1) Oleic acid, linoleic acid, glyceryl trilinoleate, beta-stigmasterol
      and coixol inhibited the expression of MUC5AC mucin gene induced by PMA from NCI
      H292 cells; (2) Oleic acid, linoleic acid, glyceryl trilinoleate, beta
      stigmasterol and coixol also inhibited the production of MUC5AC mucin protein
      induced by the same inducers from NCI-H292 cells; (3) Coixol inhibited the
      expression of MUC5AC mucin gene and production of MUC5AC mucin protein, induced
      by EGF or TNF-alpha from NCI-H292 cells; (4) Coixol decreased PMA-induced MUC5AC
      mucin secretion from NCI-H292 cells. This result suggests that coixol, the
      characteristic component among the examined five natural products derived from C.
      Lachryma-Jobi var. ma-yuen, can regulate gene expression, production and
      secretion of mucin, by directly acting on airway epithelial cells. 

PMID- 24733674
TI  - Cantharidin inhibits angiogenesis by suppressing VEGF-induced JAK1/STAT3, ERK and
      AKT signaling pathways.
AB  - Cantharidin (CTD), a chemical compound secreted by blister beetles, has been
      shown with anti-tumor property in many cancer cells. In this study, our data
      showed that CTD exerts potent anti-angiogenesis activity in a dose-dependent
      manner. CTD dose dependently suppressed human umbilical vascular endothelial
      cells proliferation, migration, and tube formation in vitro. Furthermore, CTD
      concentration dependently inhibited angiogenesis in chick embryo CAM model in
      vivo. At the molecular level, CTD abrogated VEGF-induced activation of STAT3 and
      suppressed the phosphorylation of JAK1 and ERK in a dose-dependent manner.
      Furthermore, CTD blocked the phosphorylation of AKT in a time-dependent manner.
      Taken together, these findings clearly demonstrate for the first time that CTD
      can inhibit angiogenesis and may have applications in the development of new anti
      angiogenesis drugs.

PMID- 24733675
TI  - Triterpenoid saponins from the roots of Rosa rugosa Thunb. as rat intestinal
      sucrase inhibitors.
AB  - Medicinal plants constitute an important source of potential therapeutic agents
      for diabetes. The purpose of present study is to investigate the effect of root
      extract of Rosa rugosa Thunb. on inhibition of sucrase related to diabetes
      mellitus (DM). Bioassay-guided fractionation of the methanol extract led to the
      identification of 13 triterpenoid saponins (1-13). Their structures were
      elucidated on the basis of extensive spectroscopic analysis, including 1D, 2D
      NMR, and MS. The n-butanol fraction showed potent rat intestinal sucrase
      inhibitory activity with value of 87.62 +/- 5.84 % inhibition compared to the
      positive control acarbose (50.96 +/- 2.97 % inhibition at 0.02 mM). Subsequently,
      compounds 11-13 (1.0 mM) exhibited significant sucrase inhibitory activity, with
      inhibition percentage values of 41.17 +/- 3.52, 46.80 +/- 4.00, and 39.39 +/-
      4.19 %, respectively. Whereas, compounds 2-6, 8, and 10 showed moderate sucrase
      inhibitory activity (ranging from 13.26 +/- 7.00 to 32.08 +/- 6.04 % inhibition)
      at a same concentration. The data provide a starting point for creating new
      sucrase inhibitors, which may be useful for the development of effective
      therapies for the treatment of DM. 

PMID- 24733676
TI  - Antiangiogenic effects of cucurbitacin-I.
AB  - Cucurbitacin-I is a naturally occurring tetracyclic triterpenoid compound with
      diverse physiological actions that include inducing apoptosis and blocking cell
      cycle progression of various cancer cells. However, its antiangiogenic activity
      has not yet been examined. Accordingly, we investigated the antiangiogenic
      efficacy and associated mechanisms of cucurbitacin-I in vitro using human
      umbilical vein endothelial cells (HUVECs). Cucurbitacin-I inhibited HUVEC
      proliferation, invasion, migration and tubule formation, as well as angiogenic
      activity by rat aorta explants. Notably, cucurbitacin-I inhibited phosphorylation
      of vascular endothelial growth factor receptor-2 and fibroblast growth factor
      receptor-1, which are key regulators of endothelial cell function and
      angiogenesis. In vivo matrigel plug assay in mice showed significant decrease in
      vascularization and hemoglobin content in the plugs from cucurbitacin-I-treated
      mice, compared with control mice. Overall, these results suggest that
      cucurbitacin-I inhibits various attributes of angiogenesis, which might
      contribute to its reported antitumor effects. Cucurbitacin-I warrants further
      investigation as an angiogenesis inhibitor for use in cancer treatment.

PMID- 24733677
TI  - IgG4-related hypertrophic pachymeningitis: clinical features, diagnostic
      criteria, and treatment.
AB  - IMPORTANCE: IgG4-related hypertrophic pachymeningitis (IgG4-RHP) is an
      increasingly recognized manifestation of IgG4-related disease, a
      fibroinflammatory condition that can affect virtually any organ. It is estimated
      that IgG4-RHP may account for a high proportion of cases of hypertrophic
      pachymeningitis once considered idiopathic. OBJECTIVE: To summarize the current
      knowledge on IgG4-RHP including its pathological, clinical, and radiological
      presentations. Particular emphasis is placed on diagnostic and therapeutic
      implications. EVIDENCE REVIEW: This review is based on 21 reports published in
      the English medical literature since 2009. PubMed was searched with the following
      terms: IgG4, pachymeningitis, IgG4-related pachymeningitis, IgG4-related disease,
      IgG4-related, and IgG4 meningitis. Only cases with biopsy-proven IgG4-RHP were
      considered and included in this review. FINDINGS: Little is known with certainty
      regarding the pathogenesis of IgG4-RHP. The presence of oligoclonally restricted
      IgG4-positive plasma cells within inflammatory meningeal niches strongly suggests
      a specific response against a still unknown antigen. Clinical presentation of
      IgG4-RHP is not distinguishable from other forms of hypertrophic pachymeningitis
      and reflects mechanical compression of vascular or nerve structures, leading to
      functional deficits. Signs of systemic IgG4-related disease may concomitantly be
      present. Diagnostic process should rely primarily on magnetic resonance imaging,
      cerebrospinal fluid analysis, and meningeal biopsy. In particular, hallmark
      histopathological features of IgG4-RHP are a lymphoplasmacytic infiltration of
      IgG4-positive plasma cells, storiform fibrosis, and obliterative phlebitis. High
      dose glucocorticoids are still the treatment of choice for IgG4-RHP because
      immunosuppressive agents have shown variable efficacy in reducing the meningeal
      hypertrophy. Rituximab is a promising therapeutic approach but experience with B
      cell depletion strategies remains limited. CONCLUSIONS AND RELEVANCE: IgG4
      related disease accounts for an increasing proportion of cases of idiopathic
      hypertrophic pachymeningitis. Clinicians should become familiar with this
      alternative differential diagnosis because a prompt, specific therapeutic
      approach may avoid long-term neurological complications.

PMID- 24733678
TI  - Effect of Aloe vera (Aloe barbadensis Miller) on survivability, extent of
      proteolysis and ACE inhibition of potential probiotic cultures in fermented milk.
AB  - BACKGROUND: In the present investigation, the effect of Aloe vera gel powder on
      angiotensin-converting enzyme (ACE) inhibitory activity, extent of proteolysis
      during fermentation and survival of Lactobacillus casei NCDC19 during storage of
      fermented milk was studied. RESULTS: Among the different cultures screened for
      ACE inhibitory activity, Lactobacillus casei NCDC 19 exhibited the highest ACE
      inhibition (approx. 40%) as well as extent of proteolysis (0.37, Abs340). In the
      presence of Aloe vera (0.5% and 1% w/v) an increase in extent of proteolysis
      (0.460 +/- 0.047 and 0.480 +/- 0.027) and percent ACE inhibitory activity (44.32
      +/- 2.83 and 47.52 +/- 1.83) was observed in comparison to control. Aloe vera
      powder addition also led to an increase in viable counts (>11 log cfu mL-1) of L.
      casei NCDC 19 in fermented milk during storage for 7 days and the counts were
      maintained in sufficiently higher numbers. CONCLUSION: The study suggests Aloe
      vera to be a good functional ingredient which can be further explored for
      different health attributes.

PMID- 24733679
TI  - Clinical course and prognosis in ulcerative colitis: results from population
      based and observational studies.
AB  - The clinical course of ulcerative colitis (UC) may range from a quiescent course
      with prolonged periods of remission to fulminant disease requiring intensive
      medical treatment or surgery. Disease outcome is often determined by relapse
      rates, the development of colorectal cancer (CRC) and mortality rates. Early
      patient classification, identifying those with a high risk of developing
      complicated disease, is essential for choosing appropriate treatment. This paper
      reviews the clinical outcomes of UC patients as reported in population-based and
      observational studies representative of the whole patient population. Extensive
      colitis, a high level of systemic symptoms and young age at diagnosis are factors
      associated with a high risk of colectomy. Patients with distal disease who
      progress to extensive colitis seem to be a subgroup with an especially high risk
      of colectomy. Some prognostic factors of severe disease have been identified
      which could be used to optimize treatment and possibly reduce future
      complications. The overall risk of CRC and mortality was not significantly
      different from that of the background population. These results may have
      implications for follow-up strategies, especially regarding endoscopic
      surveillance of UC patients.

PMID- 24733680
TI  - A randomized controlled trial of illness management and recovery with an active
      control group.
AB  - OBJECTIVE: The purpose of the study was to rigorously test Illness Management and
      Recovery (IMR) against an active control group in a sample that included
      veterans. METHODS: A total of 118 participants with schizophrenia spectrum
      disorders, 56 of whom were veterans, were recruited from a Department of Veterans
      Affairs medical center and a community mental health center in the same city and
      were randomly assigned to an IMR group (N=60) or a weekly problem-solving group
      intervention (N=58). Groups met weekly for nine months. Blinded assessments were
      conducted at baseline, nine months, and 18 months on measures of symptoms,
      functioning, illness self-management, medication adherence, subjective recovery
      experiences, and service utilization. RESULTS: No significant differences were
      found between IMR and problem-solving groups. Participants in both groups
      improved significantly over time in symptom severity, illness management, and
      quality of life and had fewer emergency department visits. Participation rates in
      both interventions were low. Only 28% of consumers assigned to IMR and 17% of
      those assigned to the problem-solving group participated in more than half the
      scheduled groups, and 23% and 34%, respectively, attended no sessions.
      CONCLUSIONS: This is the first randomized controlled trial of IMR to report
      negative findings. Given the inclusion of an active control group and the low
      participation rates, further research is needed to understand factors affecting
      IMR effectiveness. Increased attention may need to be paid to facilitate more
      active participation in IMR, such as individual follow-up with consumers and the
      integration of IMR with ongoing treatment.

PMID- 24733681
TI  - Authors' reply to Hodson and colleagues.

PMID- 24733683
TI  - Overcoming NHCs neutrality: installing tetracarbenes on group 13 and 14 metals.
AB  - The first tetracarbene complexes of group 13 and 14 metals have been synthesized
      by employing dianionic macrocyclic tetracarbene ligands. The tin, indium, and
      aluminium tetracarbene complexes are structurally analogous to their porphyrin or
      salen analogues. The aluminium complex is the first example of multiple NHCs
      bound to this metal centre. 

PMID- 24733682
TI  - The utility of the Edinburgh Depression Scale as a screening tool for depression
      in Parkinson's disease.
AB  - OBJECTIVE: This study aimed to evaluate the Edinburgh Depression Scale (EDS) as a
      screening tool for use in a Parkinson's disease (PD) population. Many commonly
      used depression scales include items relating to somatic symptoms that also occur
      in PD, which could potentially result in inaccurate reporting of depressive
      symptoms. The EDS is a scale that incorporates no somatic items. METHOD: One
      hundred twenty patients attending specialist PD clinics were assessed using a
      standardised diagnostic interview (Present State Examination--Schedules for
      Clinical Assessment in Neuropsychiatry) to establish a diagnosis of DSM-IV
      depression. They later completed the EDS with another researcher who was blind to
      the results of diagnostic interview. A receiver operating characteristic curve
      analysis was carried out to identify the optimal threshold score on the EDS and
      the Brief EDS to identify any depressive disorder or major depression. The
      performance characteristics at a range of thresholds were compared. RESULTS: A
      cut-off score of 10/11 gave maximal discriminant validity, with 74% sensitivity,
      92% specificity and 64% positive predictive value for the identification of any
      depression according to DSM-IV criteria. CONCLUSIONS: This study suggests that
      the EDS is both a valid and potentially useful instrument that can be used as a
      quick self-completion questionnaire for screening for depression in people who
      have PD.

PMID- 24733684
TI  - Ultra-performance LC separation and quadrupole time-of-flight MS identification
      of major alkaloids in Plumula Nelumbinis.
AB  - INTRODUCTION: As an essential medicine and tea source in many countries, Plumula
      Nelumbinis potentially exerts its major biological activities through its
      alkaloids. However, the activities of Plumula Nelumbinis are not fully understood
      due to the lack of studies on its chemical components. OBJECTIVE: To establish an
      ultra-performance liquid chromatography combined with diode-array detector
      (UPLC/DAD) method, coupled to an electrospray ionisation with quadrupole time-of
      flight mass spectrometry (ESI/QTOF/MS) method, for the separation and
      identification of Plumula Nelumbinis alkaloids. METHODS: The eluant from an UPLC
      separation of an ethanol extract of Plumula Nelumbinis was directly infused into
      an ESI/QTOF/MS system. Both positive and negative ion modes of ESI with low and
      high collision energy (CE) were used to obtain sufficient MS information.
      RESULTS: Twenty-one alkaloids were tentatively identified based on their
      chromatographic characteristics, UV spectra, exact mass, MS fragments and
      literature reports. They consist of six bis-1-benzyltetrahydroisoquinoline,
      eleven benzyltetrahydroisoquinoline (including two glycoalkaloids and two
      quaternary ammoniums), two aporphine, one proaporphine and one indole alkaloids.
      Eleven were identified in Plumula Nelumbinis for the first time and seven were
      first reported in Nelumbo nucifera Gaertn. Five compounds, namely norcoclaurine
      4'-O-glucoside, norcoclaurine-6-O-glucoside, isolotusine, 6-demethyl-4-demethylN
      methylcoclaurine and N-norisoliensinine, were characterised and proposed as new
      compounds. CONCLUSION: The established UPLC/DAD - ESI/QTOF/MS method is efficient
      for systematic identification of the alkaloids in Plumula Nelumbinis extract.

PMID- 24733685
TI  - A new therapeutic community: development of a compassion-focussed and contextual
      behavioural environment.
AB  - Social relationships and communities provide the context and impetus for a range
      of psychological developments, from genetic expression to the development of core
      self-identities. This suggests a need to think about the therapeutic changes and
      processes that occur within a community context and how communities can enable
      therapeutic change. However, the 'therapeutic communities' that have developed
      since the Second World War have been under-researched. We suggest that the
      concept of community, as a change process, should be revisited within mainstream
      scientific research. This paper briefly reviews the historical development of
      therapeutic communities and critically evaluates their current theory, practice
      and outcomes in a systematic review. Attention is drawn to recent research on the
      nature of evolved emotion regulation systems, the way these are entrained by
      social relationships, the importance of affiliative emotions in the regulation of
      threat and the role of fear of affiliative emotions in psychopathology. We draw
      on concepts from compassion-focussed therapy, social learning theory and
      functional analytical psychotherapy to consider how members of a therapeutic
      community can be aware of each other's acts of courage and respond using
      compassion. Living in structured and affiliative-orientated communities that are
      guided by scientific models of affect and self-regulation offers potential
      therapeutic advantages over individual outpatient therapy for certain client
      groups. This conclusion should be investigated further. Key Practitioner Message
      Current therapeutic community practice is not sufficiently evidence based and may
      not be maximizing the potential therapeutic value of a community. Compassion
      focussed therapy and social learning theory offer new approaches for a
      therapeutic environment, involving an understanding of the role, nature and
      complexities of compassionate and affiliative relationships from staff and
      members, behavioural change guided by learning theory, a clear formulation based
      on threat-derived safety strategies, goal setting and positive reinforcement.

PMID- 24733686
TI  - Submicron-scale surface architecture of tricalcium phosphate directs osteogenesis
      in vitro and in vivo.
AB  - A current challenge of synthetic bone graft substitute design is to induce bone
      formation at a similar rate to its biological resorption, matching bone's
      intrinsic osteoinductivity and capacity for remodelling. We hypothesise that both
      osteoinduction and resorption can be achieved by altering surface microstructure
      of beta-tricalcium phosphate (TCP). To test this, two TCP ceramics are engineered
      with equivalent chemistry and macrostructure but with either submicron- or micron
      scale surface architecture. In vitro, submicron-scale surface architecture
      differentiates larger, more active osteoclasts--a cell type shown to be important
      for both TCP resorption and osteogenesis--and enhances their secretion of
      osteogenic factors to induce osteoblast differentiation of human mesenchymal stem
      cells. In an intramuscular model, submicrostructured TCP forms 20 % bone in the
      free space, is resorbed by 24 %, and is densely populated by multinucleated
      osteoclast-like cells after 12 weeks; however, TCP with micron-scale surface
      architecture forms no bone, is essentially not resorbed, and contains scarce
      osteoclast-like cells. Thus, a novel submicron-structured TCP induces substantial
      bone formation and is resorbed at an equivalent rate, potentially through the
      control of osteoclast-like cells.

PMID- 24733687
TI  - Liraglutide-induced autoimmune hepatitis.
AB  - IMPORTANCE: Use of incretin-based hypoglycemic agents is increasing, but safety
      data remain limited. We treated a woman with marker-negative autoimmune hepatitis
      associated with the glucagon-like peptide 1 agonist liraglutide. OBSERVATIONS: A
      young woman with type 2 diabetes mellitus and vitiligo presented with a 10-day
      history of acute hepatitis. Other than starting liraglutide therapy 4 months
      prior, she reported no changes in medication therapy and no use of supplements.
      At admission, aspartate aminotransferase level was 991 U/L; alanine
      aminotransferase level, 1123 U/L; total bilirubin level, 9.5 mg/dL; and
      international normalized ratio, 1.3. Results of a liver biopsy demonstrated
      interface hepatitis with prominent eosinophils and rare plasma cells. The
      patient's liraglutide therapy was withheld at discharge but her symptoms
      worsened. A second biopsy specimen revealed massive hepatic necrosis. She started
      oral prednisone therapy for presumed liraglutide-induced marker-negative
      autoimmune hepatitis. CONCLUSIONS AND RELEVANCE: This case represents, to our
      knowledge, the first report of liraglutide-induced autoimmune hepatitis.
      Hepatotoxicity may be an incretin analogue class effect with a long latency
      period. This case raises prescriber awareness about the potential adverse effects
      of glucagon-like peptide 1 agonists. Postmarketing studies are needed to define
      the hepatotoxic potential of these agents.

PMID- 24733688
TI  - MRI and cardiac implantable electronic devices; current status and required
      safety conditions.
AB  - Magnetic resonance imaging (MRI) has evolved into an essential diagnostic
      modality for the evaluation of all patient categories. This gain in popularity
      coincided with an increase in the number of implanted cardiac implantable
      electronic devices (CIEDs). Therefore, questions arose with regard to the MRI
      compatibility of these devices. Various investigators have reported the harmless
      performance of MRI in patients with conventional (non-MRI conditional) devices.
      The recently published European Society of Cardiology (ESC) guidelines on cardiac
      pacing and cardiac resynchronisation therapy (CRT) indicate that MRI can be
      safely performed in patients with an implanted pacemaker or ICD (MRI conditional
      or not), as long as strict safety conditions are met. This is a major
      modification of the former general opinion that patients with a pacemaker or ICD
      were not eligible to undergo MRI. This review paper attempts to elucidate the
      current situation for practising cardiologists by providing a clear overview of
      the potential life-threatening interactions and discuss safety measures to be
      taken prior to and during scanning. An overview of all available MRI conditional
      devices and their individual restrictions is given. In addition, an up-to-date
      safety protocol is provided that can be used to ensure patient safety before,
      during and after the scan. Key points * Historically, MRI examination of patients
      with a CIED has been considered hazardous. * Ongoing advances in technology and
      increasing usage of MRI in clinical practice have led to the introduction of MRI
      conditional CIEDs and to more lenient regulations on the examination of patients
      with non-conditional CIEDs. * MRI investigations can be performed safely in
      selected patients when adhering to a standardised up-to-date safety protocol. 

PMID- 24733689
TI  - New antiarrhythmic targets to control intracellular calcium handling.
AB  - Sudden cardiac death due to ventricular arrhythmias is a major problem. Drug
      therapies to prevent SCD do not provide satisfying results, leading to the demand
      for new antiarrhythmic strategies. New targets include Ca(2+)/Calmodulin
      dependent protein kinase II (CaMKII), the Na/Ca exchanger (NCX), the Ryanodine
      receptor (RyR, and its associated protein FKBP12.6 (Calstabin)) and the late
      component of the sodium current (I Na-Late ), all related to intracellular
      calcium (Ca(2+)) handling. In this review, drugs interfering with these targets
      (SEA-0400, K201, KN-93, W7, ranolazine, sophocarpine, and GS-967) are evaluated
      and their future as clinical compounds is considered. These new targets prove to
      be interesting; however more insight into long-term drug effects is necessary
      before clinical applicability becomes reality. 

PMID- 24733690
TI  - Trends in cardiovascular disease risk factors by obesity level in adults in the
      United States, NHANES 1999-2010.
AB  - OBJECTIVE: To assess whether trends in cardiovascular disease (CVD) risk factors
      by among overweight and obese US adults have improved. METHODS: The study
      included 10,568 adults 18 years and older who participated in National Health and
      Nutrition Examination Survey 1999-2010. CVD risk factors included diabetes (self
      reported diagnosis, glycated hemoglobin >=6.5%, or fasting plasma glucose
      >=126mg/dl), hypertension (treatment or blood pressure >=140/90 mmHg),
      dyslipidemia (treatment or non-HDL cholesterol >=160 mg/dl), and smoking (self
      report or cotinine levels >=10 ng/ml). The prevalence and temporal trends of CVD
      risk factors for each BMI group were estimated. RESULTS: In 2007-2010, the
      prevalence of diabetes, hypertension, and dyslipidemia was highest among obese
      (18.5%, 35.7%, 49.7%, respectively) followed by overweight (8.2%, 26.4%, 44.2%,
      respectively) and normal weight adults (5.4%, 19.8%, 28.6%, respectively).
      Smoking exposure was highest among normal weight (29.8%) followed by overweight
      (24.8%) and obese adults (24.6%). From 1999-2002 to 2007-2010, untreated
      hypertension decreased among obese and overweight adults and untreated
      dyslipidemia decreased for all weight groups. There were no significant temporal
      changes in smoking across BMI groups. CONCLUSIONS: Despite decreases in untreated
      risk factors, it is important to improve the CVD risk profile of overweight and
      obese US adults.

PMID- 24733691
TI  - Fate and behavior of rotenone in Diamond Lake, Oregon, USA following invasive tui
      chub eradication.
AB  - In September 2006, Diamond Lake (OR, USA) was treated by the Oregon Department of
      Fish and Wildlife with a mixture of powdered and liquid rotenone in the
      successful eradication of invasive tui chub Gila bicolor. During treatment, the
      lake was in the middle of a phytoplankton (including cyanobacteria Anabaena sp.)
      bloom, resulting in an elevated pH of 9.7. Dissipation of rotenone and its major
      metabolite rotenolone from water, sediment, and macrophytes was monitored.
      Rotenone dissipated quickly from Diamond Lake water; approximately 75% was gone
      within 2 d, and the average half-life (t1/2) value, estimated by using first
      order kinetics, was 4.5 d. Rotenolone persisted longer (>46 d) with a short-term
      t1/2 value of 16.2 d. Neither compound was found in groundwater, sediments, or
      macrophytes. The dissipation of rotenone and rotenolone appeared to occur in 2
      stages, which was possibly the result of a release of both compounds from
      decaying phytoplankton following their initial dissipation. Fisheries managers
      applying rotenone for fish eradication in lentic environments should consider the
      following to maximize efficacy and regulatory compliance: 1) treat at a minimum
      of twice the minimum dose demonstrated for complete mortality of the target
      species and possibly higher depending on the site's water pH and algae abundance,
      and 2) implement a program that closely monitors rotenone concentrations in the
      posttreatment management of a treated water body.

PMID- 24733692
TI  - Mechanical ventilation in acute hypoxemic respiratory failure: a review of new
      strategies for the practicing hospitalist.
AB  - BACKGROUND: The goal of mechanical ventilation in acute hypoxemic respiratory
      failure is to support adequate gas exchange without harming the lungs. How
      patients are mechanically ventilated can significantly impact their ultimate
      outcomes. METHODS: This review focuses on emerging evidence regarding strategies
      for mechanical ventilation in patients with acute hypoxemic respiratory failure
      including: low tidal volume ventilation in the acute respiratory distress
      syndrome (ARDS), novel ventilator modes as alternatives to low tidal volume
      ventilation, adjunctive strategies that may enhance recovery in ARDS, the use of
      lung-protective strategies in patients without ARDS, rescue therapies in
      refractory hypoxemia, and an evidence-based approach to weaning from mechanical
      ventilation. RESULTS: Once a patient is intubated and mechanically ventilated,
      low tidal volume ventilation remains the best strategy in ARDS. Adjunctive
      therapies in ARDS include a conservative fluid management strategy, as well as
      neuromuscular blockade and prone positioning in moderate-to-severe disease. There
      is also emerging evidence that a lung-protective strategy may benefit non-ARDS
      patients. For patients with refractory hypoxemia, extracorporeal membrane
      oxygenation should be considered. Once the patient demonstrates signs of
      recovery, the best approach to liberation from mechanical ventilation involves
      daily spontaneous breathing trials and protocolized assessment of readiness for
      extubation. CONCLUSIONS: Prompt recognition of ARDS and use of lung-protective
      ventilation, as well as evidence-based adjunctive therapies, remain the
      cornerstones of caring for patients with acute hypoxemic respiratory failure. In
      the absence of contraindications, it is reasonable to consider lung-protective
      ventilation in non-ARDS patients as well, though the evidence supporting this
      practice is less conclusive.

PMID- 24733693
TI  - INDs for PET molecular imaging probes-approach by an academic institution.
AB  - We have developed an efficient, streamlined, cost-effective approach to obtain
      Investigational New Drug (IND) approvals from the Food and Drug Administration
      (FDA) for positron emission tomography (PET) imaging probes (while the FDA uses
      the terminology PET drugs, we are using "PET imaging probes," "PET probes," or
      "probes" as the descriptive terms). The required application and supporting data
      for the INDs were collected in a collaborative effort involving appropriate
      scientific disciplines. This path to INDs was successfully used to translate
      three [(18) F]fluoro-arabinofuranosylcytosine (FAC) analog PET probes to phase 1
      clinical trials. In doing this, a mechanism has been established to fulfill the
      FDA regulatory requirements for translating promising PET imaging probes from
      preclinical research into human clinical trials in an efficient and cost
      effective manner.

PMID- 24733694
TI  - Studies on the antioxidant activity of some thiazolidinedione, imidazolidinedione
      and rhodanine derivatives having a flavone core.
AB  - A series of flavonyl-2,4-thiazolidinedione, imidazolidinedione and rhodanine
      derivatives were tested for their antioxidant activity as scavengers of oxygen
      free radicals. Free radical scavenging activities, including superoxide anion
      radical O2*, hydroxyl radical (HO(*)) and 2,2'-diphenyl-1-picrylhydrazyl free
      radical have been evaluated using chemiluminescence, electron paramagnetic
      resonance and spin trapping with 5,5-dimethyl-1-pyrroline-1-oxide as a spin trap.
      Potassium superoxide in dimethylsulfoxide and 18-crown-6 ether were used for the
      production of O2*. Hydroxyl radical was generated using the Fenton reaction. Ten
      of the eleven examined compounds exhibited decrease in chemiluminescence, but
      there were large differences in the decrease, ranging from 16% to 89%; also, two
      of these compounds increased light emission by about 200%. On the contrary, all
      compounds tested exhibited 30-68% scavenging HO(*) and 25-96% scavenging the
      DPPH(*) radical respectively. Possible mechanisms are proposed to explain the
      results.

PMID- 24733695
TI  - Pain in care home residents with dementia: an exploration of frequency,
      prescribing and relatives' perspectives.
AB  - OBJECTIVES: This study aims to determine pain frequency amongst care home
      residents with dementia, to investigate variables associated with pain, to
      explore analgesic use among residents and to seek residents' relatives' views on
      provision of care and management of pain by the care home. METHODS: Structured
      face-to-face interviews were conducted with residents, nursing staff and
      relatives from nine dementia care homes in Northern Ireland, between May 2010 and
      March 2012. Demographic information was collected from participants,
      neuropsychiatric tests were used to assess residents' cognitive functioning,
      medication use was determined from care home records and residents' pain was
      assessed using a verbal descriptor scale. Relatives' views were sought on care
      provision and management of pain. RESULTS: Forty-two residents, 16 nurses/care
      assistants and 35 relatives participated; the participation rate of residents was
      low (27.6%). Most residents were suffering moderate-severe dementia, and some
      residents (26.2%) were unable to provide a self-report of pain. A significantly
      higher proportion of relatives (57.1%) deemed residents to be experiencing pain
      at the time of the interview, compared with residents (23.8%, p = 0.005) and
      nurses/care assistants (42.9%, p = 0.035). Most residents (88.1%) were prescribed
      with analgesia; non-opioid analgesics were most commonly prescribed. High
      proportions of residents were prescribed with psychoactive medications.
      Antipsychotic drug use was associated with presence of pain (p = 0.046).
      CONCLUSIONS: This study has reinforced the challenge of assessing and managing
      pain in this resident population and highlighted issues to be addressed by long
      term care providers and clinicians. Participation of people with dementia, and
      their families, in healthcare research needs to be improved.

PMID- 24733696
TI  - [Teleradiology - update 2014].
AB  - Due to economic considerations and thanks to technological advances there is a
      growing interest in the integration of teleradiological applications into the
      regular radiological workflow. The legal and technical hurdles which are still to
      be overcome are being discussed in politics as well as by national and
      international radiological societies. The European Commission as well as the
      German Federal Ministry of Health placed a focus on telemedicine with their
      recent eHealth initiatives. The European Society of Radiology (ESR) recently
      published a white paper on teleradiology. In Germany S3 section 4 of the
      Rontgenverordnung (RoV, X-ray regulations) and DIN 6868-159 set a framework in
      which teleradiology can also be used for primary reads. These possibilities are
      already being used by various networks and some commercial providers across
      Germany. With regards to cross-border teleradiology, which currently stands in
      contrast to the RoV, many issues remain unsolved.

PMID- 24733697
TI  - Action is needed to tackle current public health threats.

PMID- 24733698
TI  - A demonstration of peer support for Ugandan adults with type 2 diabetes.
AB  - BACKGROUND: By 2030, 80% of people with diabetes will be living in developing
      countries. PURPOSE: The purpose of this pre-post quasi-experimental study was to
      test the feasibility of a peer intervention to improve the following: (1)
      diabetes self-care behaviors, (2) glycemic control, (3) social support and
      emotional well-being, (4) linkages to health care providers, and (5) to assess
      the sustainability of the intervention 18 months later. METHOD: Participants were
      adults with type 2 diabetes who resided in rural Uganda. Participants (n = 46)
      attended a 1-day diabetes education program and agreed to make weekly contacts
      over 4 months with each other by phone or in person to assist with daily
      management, provide social and emotional support, and encourage appropriate
      contact with health care providers. RESULTS: Results indicated improvement in
      glycosylated hemoglobin (A1C), diastolic blood pressure, and eating behaviors.
      CONCLUSIONS: A short-term peer support program was a feasible intervention to
      improve diabetes care in rural Uganda. Participants were successfully recruited
      and retained, and they experienced positive behavioral and physiologic outcomes.
      Elements of the intervention were sustained 18 months after the intervention.

PMID- 24733699
TI  - Right hemispheric dominance of visual phenomena evoked by intracerebral
      stimulation of the human visual cortex.
AB  - Electrical brain stimulation can provide important information about the
      functional organization of the human visual cortex. Here, we report the visual
      phenomena evoked by a large number (562) of intracerebral electrical stimulations
      performed at low-intensity with depth electrodes implanted in the occipito
      parieto-temporal cortex of 22 epileptic patients. Focal electrical stimulation
      evoked primarily visual hallucinations with various complexities: simple (spot or
      blob), intermediary (geometric forms), or complex meaningful shapes (faces);
      visual illusions and impairments of visual recognition were more rarely observed.
      With the exception of the most posterior cortical sites, the probability of
      evoking a visual phenomenon was significantly higher in the right than the left
      hemisphere. Intermediary and complex hallucinations, illusions, and visual
      recognition impairments were almost exclusively evoked by stimulation in the
      right hemisphere. The probability of evoking a visual phenomenon decreased
      substantially from the occipital pole to the most anterior sites of the temporal
      lobe, and this decrease was more pronounced in the left hemisphere. The greater
      sensitivity of the right occipito-parieto-temporal regions to intracerebral
      electrical stimulation to evoke visual phenomena supports a predominant role of
      right hemispheric visual areas from perception to recognition of visual forms,
      regardless of visuospatial and attentional factors.

PMID- 24733700
TI  - Does right ventricular pacing increase the risk of ventricular arrhythmias in
      patients with an implantable cardioverter-defibrillator?

PMID- 24733701
TI  - Hypertrophic cardiomyopathy associated with abnormal origin of right coronary
      artery.

PMID- 24733702
TI  - [Infective endocarditis in patient with implantable cardiac pacemaker successful
      antibiotic treatment: two-year follow-up].

PMID- 24733703
TI  - Myocarditis and pericarditis in the course of colitis ulcerosa.

PMID- 24733704
TI  - Recurrent restenosis in saphenous vein graft. What is the next step?

PMID- 24733705
TI  - Acute anterior myocardial infarction due to stent thrombosis after bee stings.

PMID- 24733706
TI  - Superior vena cava syndrome in a 37-year-old woman with a cardioverter
      defibrillator.

PMID- 24733707
TI  - System Tornus in chronic total occlusions.

PMID- 24733708
TI  - Transcatheter aortic valve implantation: the role of transcranial Doppler
      monitoring.

PMID- 24733709
TI  - [Contemporary imaging of infective endocarditis. Infective endocarditis on
      prosthetic valves, implantable devices and right-sided location. Expert consensus
      statement of the Polish Clinical Forum for Cardiovascular Imaging].

PMID- 24733710
TI  - High rate of aspirin resistance in advanced kidney failure: does it matter?

PMID- 24733711
TI  - Diagnostic yield of head computed tomography for the hospitalized medical patient
      with delirium.
AB  - BACKGROUND: Delirium is common in hospitalized patients and warrants early
      diagnosis and treatment. Often the evaluation of delirium includes head computed
      tomography imaging. However, in hospitalized medical patients, the yield of head
      computed tomography is unknown. OBJECTIVE: To determine the diagnostic yield of
      head computed tomography when evaluating a hospitalized medical patient with
      delirium in the absence of a recent fall, head trauma, or new neurologic deficit.
      DESIGN AND SETTING: Retrospective medical record review at a large academic
      medical center in Boston, Massachusetts. PARTICIPANTS: We reviewed all medical
      records for head computed tomography scans performed from January 2010 through
      November 2012 in patients on the general medicine or medical subspecialties
      units. MAIN OUTCOMES: A "positive" head computed tomography was defined as an
      intracranial process that could explain delirium. An "equivocal" head computed
      tomography was defined as the presence of a finding of unclear significance in
      relation to delirium. RESULTS: There were 398 patients hospitalized for >24 hours
      who underwent head computed tomography for delirium. Two hundred twenty head
      computed tomography studies met eligibility criteria, with 6 (2.7%) positive and
      4 (1.8%) equivocal results. All positive and equivocal findings resulted in
      change in management. CONCLUSIONS: The diagnostic yield of head computed
      tomography in determining the cause of delirium in hospitalized patients is low.
      Due to the low rate of positive findings, head imaging is unnecessary in the
      majority of cases of delirium. However, there may be a subset of high-risk
      individuals in which head imaging is indicated.

PMID- 24733712
TI  - Contaminant exposure of birds nesting in Green Bay, Wisconsin, USA.
AB  - In earlier studies, elevated concentrations of polychlorinated biphenyl (PCB) and
      p,p'-dichlorodiphenyldichloroethylene (DDE) were reported in double-crested
      cormorant (Phalacrocorax auritus) eggs and tree swallow (Tachycineta bicolor)
      eggs and nestlings collected from lower Green Bay (WI, USA) in 1994 and 1995 and
      black-crowned night-heron (Nycticorax nycticorax) eggs collected in 1991.
      Comparable samples collected in 2010 and 2011 indicated that concentrations of
      PCBs were 35%, 62%, 70%, and 88% lower than in the early 1990s in tree swallow
      eggs, tree swallow nestlings, double-crested cormorant eggs, and black-crowned
      night-heron eggs, respectively; concentrations of DDE were 47%, 43%, 51%, and 80%
      lower, respectively. These declines are consistent with regional contaminant
      trends in other species. Concentrations of PCBs were higher in herring gull
      (Larus argentatus) than in black-crowned night-heron eggs collected from Green
      Bay in 2010; PCB concentrations in double-crested cormorant and tree swallow eggs
      were intermediate. The estimated toxicity of the PCB mixture in eggs of the
      insectivorous tree swallow was the equal to or greater than toxicity in the 3
      piscivorous bird species. A multivariate analysis indicated that the composition
      percentage of lower-numbered PCB congeners was greater in eggs of the
      insectivorous tree swallow than in eggs of the 3 piscivorous species nesting in
      Green Bay. Dioxin and furan concentrations and the toxicity of these chemicals
      were also higher in tree swallows than these other waterbird species nesting in
      Green Bay.

PMID- 24733713
TI  - A Big Five facet analysis of sub-clinical narcissism: understanding boldness in
      terms of well-known personality traits.
AB  - This study aimed to examine a Big Five 'bright-side' analysis of a sub-clinical
      personality disorder, i.e. narcissism. A total of 6957 British adults completed
      the NEO-PI-R, which measures the Big Five Personality factors at the domain and
      the facet level, as well as the Hogan Development Survey (HDS), which has a
      measure of Narcissism called Bold as one of its dysfunctional interpersonal
      tendencies. Correlation and regression results confirmed many of the associations
      between the Big Five domains and facets (NEO-PI-R) and sub-clinical narcissism.
      The Bold (Narcissism) scale from the HDS was the criterion variable in all
      analyses. Bold individuals are disagreeable extraverts with very low scores on
      facet Modesty but moderately high scores on Assertiveness, Competence and
      Achievement Striving. The study confirmed work using different population groups
      and different measures.

PMID- 24733714
TI  - Aptamer-based biosensors for biomedical diagnostics.
AB  - Aptamers are single-stranded nucleic acids that selectively bind to target
      molecules. Most aptamers are obtained through a combinatorial biology technique
      called SELEX. Since aptamers can be isolated to bind to almost any molecule of
      choice, can be readily modified at arbitrary positions and they possess
      predictable secondary structures, this platform technology shows great promise in
      biosensor development. Over the past two decades, more than one thousand papers
      have been published on aptamer-based biosensors. Given this progress, the
      application of aptamer technology in biomedical diagnosis is still in a quite
      preliminary stage. Most previous work involves only a few model aptamers to
      demonstrate the sensing concept with limited biomedical impact. This Critical
      Review aims to summarize progress that might enable practical applications of
      aptamers for biological samples. First, general sensing strategies based on the
      unique properties of aptamers are summarized. Each strategy can be coupled to
      various signaling methods. Among these, a few detection methods including
      fluorescence lifetime, flow cytometry, upconverting nanoparticles, nanoflare
      technology, magnetic resonance imaging, electronic aptamer-based sensors, and
      lateral flow devices have been discussed in more detail since they are more
      likely to work in a complex sample matrix. The current limitations of this field
      include the lack of high quality aptamers for clinically important targets. In
      addition, the aptamer technology has to be extensively tested in a clinical
      sample matrix to establish reliability and accuracy. Future directions are also
      speculated to overcome these challenges. 

PMID- 24733717
TI  - Analysis of Brain Functional Changes in High-Frequency Repetitive Transcranial
      Magnetic Stimulation in Treatment-Resistant Depression.
AB  - Repetitive transcranial magnetic stimulation (rTMS) is a treatment procedure that
      uses magnetic fields to stimulate nerve cells in the brain, and is associated
      with significant improvements in clinical symptoms of major depressive disorder
      (MDD). The effect of rTMS treatment on the brain can be evaluated by cordance, a
      quantitative electroencephalography (QEEG) method that extracts information from
      absolute and relative power of EEG spectra. In this study, to analyze brain
      functional changes, pre- and post-rTMS, QEEG data were collected from 6 frontal
      electrodes (Fp1, Fp2, F3, F4, F7, and F8) in 2 slow bands (delta and theta) for
      55 MDD subjects. To examine brain changes, cordance scores were determined, using
      repeated-measures analysis of variance (ANOVA). High-frequency rTMS was
      associated with cordance decrease in left frontal and right prefrontal regions in
      both delta and theta for nonresponders; it was associated with cordance increase
      in all right and left frontal electrodes, except F8, for responders.

PMID- 24733715
TI  - Short- and long-term effects of nocturnal oxygen therapy on sleep apnea in
      chronic heart failure.
AB  - PURPOSE: This paper studies the short- and long-term effects of nocturnal oxygen
      therapy (NOT) on sleep apnea in chronic heart failure (CHF). METHODS: We enrolled
      51 adults in New York Heart Association (NYHA) heart failure functional classes
      II or III, <=45 % left ventricular ejection fraction (LVEF), in a randomized,
      open, single-center study. Nocturnal cardiorespiratory polygraphy showed sleep
      apnea [apnea-hypopnea index (AHI) >=15 events/h] in 33 patients, of whom 19 were
      randomly assigned to NOT, 3.0 l/min, and 14 to no NOT. The NOT group underwent
      follow-up polygraphy at 24 h and 6 months, and the no NOT group a single follow
      up polygraphy at 6 months. RESULTS: No significant difference was observed
      between baseline and 6 months in the no NOT group. In the NOT group, AHI
      decreased from 36.8 +/- 2.6 events/h at baseline to 20.8 +/- 3.0 at 24 h and to
      18.3 +/- 2.4 at 6 months (both P < 0.0001 vs. baseline), due to central AHI
      changes from 23.3 +/- 2.8 events/h at baseline to 8.3 +/- 1.6 at 24 h and to 6.1
      +/- 1.4 at 6 months (both P < 0.0001 vs. baseline). Oxygen desaturation index
      (ODI) decreased from 33.0 +/- 5.2 events/h at baseline to 7.5 +/- 0.5 at 24 h and
      9.3 +/- 2.6 at 6 months (both P < 0.0001 vs. baseline). NOT had no significant
      effect on obstructive and mixed AHI, quality of life (QOL), NYHA class, and LVEF
      up to 6 months of follow-up. CONCLUSIONS: NOT decreased central AHI and ODI
      significantly within 24 h and up to 6 months in CHF patients with sleep apnea,
      without significantly modifying obstructive and mixed AHI, QOL, and ventricular
      function.

PMID- 24733716
TI  - Linking cognition and frailty in middle and old age: metabolic syndrome matters.
AB  - OBJECTIVES: This study examined whether metabolic syndrome (MetS) would moderate
      the association of cognition with frailty in middle and old age. METHODS: A cross
      sectional design was used. Six hundred and ninety participants (age >= 50 years)
      from an on-going national survey were included in the study. Confirmatory factor
      analysis was applied to determine latent variables of executive function (EF),
      episodic memory (EM), and MetS based on relevant measurements. Frailty was
      defined using a modified form of Fried's criteria. RESULTS: Applying structural
      equation modeling, having MetS significantly increased the likelihood of being
      frail. Better performance on EM tasks, but not EF, was significantly associated
      with lower likelihood of MetS. Worse performance on EF, but not EM, significantly
      increased the likelihood of being frail. There was a significant interacting
      effect between MetS and EF, but not EM, on frailty. Further contrast analysis
      indicated that having MetS strengthened the negative association between EF and
      frailty. CONCLUSION: Metabolic syndrome moderates the relationship between EF and
      frailty. A prospecitve study is needed to validate such relationships before
      developing interventions targeting the prevention or treatment of EF and frailty
      in individuals with MetS.

PMID- 24733718
TI  - Feature Selection and Classification of Electroencephalographic Signals: An
      Artificial Neural Network and Genetic Algorithm Based Approach.
AB  - Feature selection is an important step in many pattern recognition systems aiming
      to overcome the so-called curse of dimensionality. In this study, an optimized
      classification method was tested in 147 patients with major depressive disorder
      (MDD) treated with repetitive transcranial magnetic stimulation (rTMS). The
      performance of the combination of a genetic algorithm (GA) and a back-propagation
      (BP) neural network (BPNN) was evaluated using 6-channel pre-rTMS
      electroencephalographic (EEG) patterns of theta and delta frequency bands. The GA
      was first used to eliminate the redundant and less discriminant features to
      maximize classification performance. The BPNN was then applied to test the
      performance of the feature subset. Finally, classification performance using the
      subset was evaluated using 6-fold cross-validation. Although the slow bands of
      the frontal electrodes are widely used to collect EEG data for patients with MDD
      and provide quite satisfactory classification results, the outcomes of the
      proposed approach indicate noticeably increased overall accuracy of 89.12% and an
      area under the receiver operating characteristic (ROC) curve (AUC) of 0.904 using
      the reduced feature set. 

PMID- 24733719
TI  - On the limited recognition of inorganic surfaces by short peptides compared with
      antibodies.
AB  - The vast potential applications of biomolecules that bind inorganic surfaces led
      mostly to the isolation of short peptides that target selectively specific
      materials. The demonstrated differential affinity toward certain surfaces created
      the impression that the recognition capacity of short peptides may match that of
      rigid biomolecules. In the following, we challenge this view by comparing the
      capacity of antibody molecules to discriminate between the (100) and (111A)
      facets of a gallium arsenide semiconductor crystal with the capacity of short
      peptides to do the same. Applying selection from several peptide and single chain
      phage display libraries, we find a number of antibody molecules that bind
      preferentially a given crystal facet but fail to isolate, in dozens of attempts,
      a single peptide capable of such recognition. The experiments underscore the
      importance of rigidity to the recognition of inorganic flat targets and therefore
      set limitations on potential applications of short peptides in biomimetics.

PMID- 24733720
TI  - Managing facility risk: external threats and health care organizations.
AB  - Clinicians and clinical administrators should have a basic understanding of
      physical and financial risk to mental health facilities related to external
      physical threat, including actions usually viewed as "terrorism" and much more
      common sources of violence. This article refers to threats from mentally ill
      persons and those acting out of bizarre or misguided "revenge," extortionists and
      other outright criminals, and perpetrators usually identified as domestic or
      international terrorists. The principles apply both to relatively small and
      contained acts (such as a patient or ex-patient attacking a staff member) and to
      much larger events (such as bombings and armed attack), and are relevant to
      facilities both within and outside the U.S. Patient care and accessibility to
      mental health services rest not only on clinical skills, but also on a place to
      practice them and an organized system supported by staff, physical facilities,
      and funding. Clinicians who have some familiarity with the non-clinical
      requirements for care are in a position to support non-clinical staff in
      preventing care from being interrupted by external threats or events such as
      terrorist activity, and/or to serve at the interface of facility operations and
      direct clinical care. Readers should note that this article is an introduction to
      the topic and cannot address all local, state and national standards for hospital
      safety, or insurance providers' individual facility requirements.

PMID- 24733722
TI  - GSK faces accusations of bribing doctors in Poland.

PMID- 24733721
TI  - Virus-templated plasmonic nanoclusters with icosahedral symmetry via directed
      self-assembly.
AB  - The assembly of plasmonic nanoparticles with precise spatial and orientational
      order may lead to structures with new electromagnetic properties at optical
      frequencies. The directed self-assembly method presented controls the
      interparticle-spacing and symmetry of the resulting nanometer-sized elements in
      solution. The self-assembly of three-dimensional (3D), icosahedral plasmonic
      nanosclusters (NCs) with resonances at visible wavelengths is demonstrated
      experimentally. The ideal NCs consist of twelve gold (Au) nanospheres (NSs)
      attached to thiol groups at predefined locations on the surface of a genetically
      engineered cowpea mosaic virus with icosahedral symmetry. In situ dynamic light
      scattering (DLS) measurements confirm the NSs assembly on the virus. Transmission
      electron micrographs (TEM) demonstrate the ability of the self-assembly method to
      control the nanoscopic symmetry of the bound NSs, which reflects the icosahedral
      symmetry of the virus. Both, TEM and DLS show that the NCs comprise of a
      distribution of capsids mostly covered (i.e., 6-12 NS/capsid) with NSs. 3D finite
      element simulations of aqueous suspensions of NCs reproduce the experimental bulk
      absorbance measurements and major features of the spectra. Simulations results
      show that the fully assembled NCs give rise to a 10-fold surface-averaged
      enhancement of the local electromagnetic field. 

PMID- 24733723
TI  - Error disclosure how to say, "I'm sorry.".

PMID- 24733724
TI  - Comparison of access, outcomes and experiences of older adults and working age
      adults in psychological therapy.
AB  - OBJECTIVE: This study aimed to evaluate the access, experiences and outcomes of
      older adults receiving psychological therapies in comparison with adults of
      working age METHODS: Primary and secondary care providers of psychological
      therapy services participated in the National Audit of Psychological Therapies.
      The main standards of access, experience and outcomes were measured by
      retrospective case records audits of people who completed therapy and a service
      user questionnaire. Outcomes were measured pre-treatment and post-treatment on
      the PHQ-9 and GAD-7. RESULTS: A total of 220 services across 97 organisations
      took part, 137 (62%) in primary care. Service user questionnaires were received
      from 14 425 (20%) respondents. A total of 122 740 records were audited, of whom
      7794 (6.4%) were older adults. They were under represented as 13% of the sample
      would have been expected to be over 65 years according to age adjusted
      psychiatric morbidity figures. People over 75 years had the third expected
      referral rate. Significantly, more older adults than working age adults completed
      therapy (59.6% vs 48.6%) and were assessed as having 'recovered' post-treatment
      (58.5% vs 45.5%). Older adults were more satisfied with waiting times and numbers
      of sessions, but there were no differences in self-reported experience of
      therapy. CONCLUSION: Although older adults are less likely to gain access to
      psychological therapies, they appear to have better outcomes than working age
      adults. Further work is needed to improve access for older people.

PMID- 24733725
TI  - Positive impact of a master of science in applied anatomy program on USMLE Step 1
      performance.
AB  - In this retrospective study of medical student data from Case Western Reserve
      University School of Medicine, we examined the impact of the Master of Science in
      Applied Anatomy (MS) program on medical student performance on the United States
      Medical Licensing Examination((r)) (USMLE((r))) Step 1 and Step 2. From 2002 to
      2010, 1,142 students matriculated as either students in the medical curriculum
      (MD group; 1,087 students) or MD students who also participated in the MS program
      (MD/MS group; 55 students). In addition, students were grouped as in either the
      Western Reserve Curriculum (2002-2005; WR1) or the Western Reserve 2 Curriculum
      (2006-2010; WR2). Data were analyzed using SPSS statistical package. The mean
      Medical College Admission Test((r)) (MCAT((r))) score of all students increased
      significantly between the WR1 and WR2 curricula [from 32.48 +/- 3.73 to 34.00 +/-
      2.92 (P < 0.00)], but MD and MD/MS students showed similar mean MCAT scores in
      each curriculum. In contrast, the mean USMLE Step 1 score for the MD/MS group
      (241.45 +/- 18.90) was significantly higher than that of the MD group (229.93 +/-
      20.65; P < 0.00). The MD/MS group in the WR2 curriculum showed significantly
      higher USMLE Step 1 scores than the MD group. No significant difference was
      observed in the USMLE Step 2 Clinical Knowledge scores between the groups. The
      results show that MD/MS students performed better on the USMLE Step 1 than MD
      students in the WR2 curriculum, although MCAT scores were similar between the two
      groups. Together, these results suggest that medical student participation in the
      Masters in Applied Anatomy program enhances student performance on the USMLE Step
      1.

PMID- 24733726
TI  - Heritability and lifestyle factors in chronic low back pain: results of the
      Australian twin low back pain study (The AUTBACK study).
AB  - BACKGROUND: Heritability and population-specific lifestyle factors are considered
      to significantly contribute to chronic low back pain (LBP), but traditional
      population studies fail to (1) adjust for genetics; and (2) use standard and
      validated definitions for LBP and for lifestyle factors. METHODS: Using a
      classical and a co-twin control study design and validated definitions for
      chronic LBP and lifestyle variables, we explored the relative contribution of
      genetics and environment on the prevalence of chronic LBP in a sample of adult
      Australian twins. RESULTS: Data from 105 twin pairs showed that the prevalence of
      chronic LBP is significantly determined by genetic factors (heritability = 32%).
      Additionally, monozygotic twins were five times more likely to have chronic LBP
      than dizygotic twins when one of the siblings of the pair was affected. In a case
      control analysis (n = 38 twin pairs), an exploratory analysis showed higher
      prevalence of chronic LBP associated with light walking exercises and vigorous
      gardening or heavy work around the house. Daily time spent in sitting was also
      positively associated with chronic LBP, but not moderate physical activities such
      as jogging, cycling and gentle swimming. In the final multivariate model, only
      time spent in vigorous gardening or heavy work around the house remained
      associated with chronic LBP (odds ratio 6.5; 95% confidence interval 1.47-28.8).
      CONCLUSIONS: The type, frequency and duration of physical activity may be
      important to understand risk factors for chronic LBP. The causation path between
      chronic LBP and people's engagement in activities involving frequent bending and
      twisting such as gardening and housework should be further investigated.

PMID- 24733732
TI  - From suffering to caring: a model of differences among older adults in levels of
      compassion.
AB  - OBJECTIVE: Compassion is an important contributor to pro-social behavior and
      maintenance of interpersonal relationships, yet little is known about what
      factors influence compassion in late life. The aim of this study was to test
      theories about how past and current stressors and emotional functioning,
      resilience, and demographic indicators of life experiences are related to
      compassion among older adults. METHODS: One thousand and six older adults (50-99
      years) completed a comprehensive survey including self-report measures of
      compassion, resilience, past and present stress, and emotional functioning (i.e.,
      stressful life events, perceived stress, and current and prior depression and
      anxiety), and demographic information. The sample was randomly split, and
      exploratory and confirmatory regression analyses were conducted testing
      hypothesized relationships with compassion. RESULTS: Exploratory stepwise
      regression analysis (n = 650) indicated that participants who reported higher
      levels of compassion were more likely to be female, not currently in a
      married/married-like relationship, reported higher resilience levels, and had
      experienced more significant life events. Age, income level, past and current
      mental distress, and interactions between resilience and other predictors were
      not significantly related to compassion. The associations between greater self
      reported compassion and being female, having greater resilience, and having
      experienced more significant life events were supported by a confirmatory
      stepwise regression analysis (n = 356). CONCLUSIONS: Older women report more
      compassion than older men. Resilience and significant life events, independently,
      also appear to facilitate a desire to help others, while current stress and past
      and present emotional functioning are less relevant. Specificity of findings to
      older adults is not yet known.

PMID- 24733733
TI  - Effect of a home intervention program on pediatric asthma in an environmental
      justice community.
AB  - Asthma prevalence rates are at an all-time high in the United States with over 25
      million persons diagnosed with asthma. African Americans and other minorities
      have higher asthma prevalence and higher exposure to environmental factors that
      worsen asthma as compared to Caucasians. This article describes the evaluation of
      an inner-city home-based asthma education and environmental remediation program
      that addressed both indoor and outdoor triggers through collaboration between a
      health system and local environmental justice organization. The program enrolled
      132 children older than 2.5 years and centers on a 4- to 6-week intervention with
      peer counselors using the U.S. Environmental Protection Agency Asthma Home
      Environment Checklist and the You Can Control Asthma curriculum. Families receive
      asthma-friendly environmental home kits. Peer counselors reinforce key asthma
      management messages and facilitate the completion of Asthma Action Plans. The
      environmental justice community partner organized block cleanups to reduce
      outdoor triggers. The evaluation used a pretest-posttest design to assess changes
      in client behavior and asthma symptoms. Data were collected at baseline and
      during a 6-month postintervention period. Participants saw enhanced conditions on
      asthma severity and control. The improvement was greatest for children whose
      asthma was considered "severe" based on the validated Asthma Control Test. Other
      positive results include the following: greater completion of Asthma Action
      Plans, significant reduction in the number of emergency room visits (p = .006),
      and substantial decreases in school absenteeism (p = .008) and use of rescue
      medications (p = .049). The evaluation suggests that the program was effective in
      improving asthma self-management in a high-risk population living within an
      environmental justice community. 

PMID- 24733734
TI  - Has Britain solved its teenage pregnancy problem?

PMID- 24733735
TI  - Nasopharyngeal squamous cell carcinoma: a comparative analysis of keratinizing
      and nonkeratinizing subtypes.
AB  - BACKGROUND: Nasopharyngeal squamous cell carcinoma (NPSCC) is uncommon in non
      endemic regions. Two major histologic subtypes are recognized: keratinizing (K
      NPSCC) and nonkeratinizing (NK-NPSCC). We hypothesize that significant
      differences exist between the 2 in terms of demographic, clinicopathologic,
      survival, and prognostic features. We aim to show that differentiating between
      the 2 subtypes is perhaps the most important first step at the time of diagnosis.
      METHODS: Using a retrospective cohort design, the U.S. National Cancer
      Institute's Surveillance, Epidemiology, and End Results (SEER) registry was used
      to extract data on the 2 major subtypes of NPSCC. Frequency, incidence, and
      relative survival (RS) were analyzed comparatively. Regression analysis was
      conducted and hazard ratios (HRs) calculated. RESULTS: A total of 1624 cases were
      identified: 1234 (76.0%) cases of NK-NPSCC and 390 (24.0%) cases of K-NPSCC. Five
      year RS was 60.6% for NK-NPSCC and 40.5% for K-NPSCC. Regression analysis
      revealed K-NPSCC to be a poor prognostic factor (HR 2.1; 95% confidence interval,
      1.8-2.6; p < 0.0001). Other factors associated with a poor prognosis included
      female gender in K-NPSCC, age greater than 44 years in both groups, and advanced
      stage disease at diagnosis. Favorable prognostic factors included Asian/Pacific
      Islander race, and treatment with radiation therapy. Higher histologic grade did
      not portend a worse prognosis for either group. CONCLUSION: NPSCC remains an
      uncommon malignancy in the United States. K-NPSCC and NK-NPSCC represent 2
      different histologic entities with important clinical differences. K-NPSCC
      carries a worse overall prognosis when compared to NK-NPSCC.

PMID- 24733737
TI  - Glycodelin-A treatment reduces the adverse effect of macrophage co-culture on
      human sperm motility.

PMID- 24733736
TI  - Role of alpha2beta1 integrins in mediating cell shape on microtextured titanium
      surfaces.
AB  - Surface microroughness plays an important role in determining osteoblast behavior
      on titanium. Previous studies have shown that osteoblast differentiation on
      microtextured titanium substrates is dependent on alpha-2 beta-1 (alpha2beta1)
      integrin signaling. This study used focused ion beam milling and scanning
      electron microscopy, combined with three-dimensional image reconstruction, to
      investigate early interactions of individual cells with their substrate and the
      role of integrin alpha2beta1 in determining cell shape. MG63 osteoblast-like
      cells on sand blasted/acid etched (SLA) Ti surfaces after 3 days of culturing
      indicated decreased cell number, increased cell differentiation, and increased
      expression of mRNA levels for alpha1, alpha2, alphaV, and beta1 integrin subunits
      compared to cells on smooth Ti (PT) surfaces. alpha2 or beta1 silenced cells
      exhibited increased cell number and decreased differentiation on SLA compared to
      wild-type cells. Wild-type cells on SLA possessed an elongated morphology with
      reduced cell area, increased cell thickness, and more apparent contact points.
      Cells on PT exhibited greater spreading and were relatively flat. Silenced cells
      possessed a morphology and phenotype similar to wild-type cells grown on PT.
      These observations indicate that surface microroughness affects cell response via
      alpha2beta1 integrin signaling, resulting in a cell shape that promotes
      osteoblastic differentiation.

PMID- 24733738
TI  - Pain reactivity in preterm neonates: examining the sex differences.
AB  - BACKGROUND: Early and repeated experiences of pain may have long-term effects on
      vulnerable newborns hospitalized in the Neonatal Intensive Care Unit (NICU), and
      neonatal pain responses may be affected by a variety of factors that neonates
      encounter. We tested the hypothesis that male preterm neonates exhibited greater
      pain sensitivity than females by assessing biobehavioural pain reactivity and
      recovery patterns to painful procedure. METHODS: Fifty-three infants born preterm
      and low birthweight who were admitted to NICU were observed during five phases
      (baseline, antisepsis, puncture, recovery-dressing and recovery-resting).
      Behavioural pain reactivity was measured using the Neonatal Facial Coding System
      (NFCS) and the Sleep-Wake States Scale (SWS). The heart rate (HR) was
      continuously recorded. All measures were assessed based on scores and magnitude
      of responses. RESULTS: We found that male and female preterm neonates had similar
      patterns of behavioural pain reactivity and recovery; there were no statistical
      differences between groups in NFCS and SWS scores. However, male preterm infants
      presented higher HR immediately in the first minute of the puncture phase and
      also higher change in maximum HR between the baseline and puncture phases, than
      female preterm infants. CONCLUSION: Although we found that male infants showed
      higher physiological reactivity to painful stimulus in some HR parameters than
      female infants, the evidences were not sufficient to confirm the influence of sex
      on biobehavioural response to pain in vulnerable neonates.

PMID- 24733739
TI  - Rapid-Steady-State-T1 signal modeling during contrast agent extravasation: toward
      tumor blood volume quantification without requiring the arterial input function.
AB  - PURPOSE: This study demonstrates how to quantify the tumor blood volume fraction
      (BVf) using the dynamic Rapid-Steady-State-T1 (RSST1 )-MRI method despite
      contrast agent (CA) leakage and without arterial input function (AIF)
      determination. METHODS: For vasculature impermeable to CAs, the BVf is directly
      quantified from the RSST1 signal amplitude. In case of CA extravasation, we
      propose a two-compartment model to describe the dynamic RSST1 signal increase. We
      applied the mathematical model in a pilot-study on a RG2-glioma model to compare
      extravasation of two Gd-based CAs. The BVf quantification using the mathematical
      model in a C6-glioma model (n = 8) with the clinical CA Gd-DOTA was validated
      using a DeltaR2 *-steady-state MRI method with an USPIO and by
      immunohistochemical staining of perfused vessels labeled with Hoechst-33342 dye
      in the same rats. RESULTS: BVf in tumor and in healthy brain tissues (0.034 +/-
      0.005 and 0.026 +/- 0.004, respectively) derived from the dynamic RSST1 signal
      were confirmed by DeltaR2 *-steady-state MRI (0.036 +/- 0.003 and 0.027 +/-
      0.002, respectively, correlation coefficient rS = 0.74) and by histology (0.036
      +/- 0.003 and 0.025 +/- 0.004 respectively, rS = 0.87). CONCLUSION:
      Straightforward tumor BVf quantification without AIF determination is
      demonstrated in presence of CA leakage. The method will facilitate angiogenesis
      assessment in longitudinal neuro-oncologic studies in particular when monitoring
      the response to antiangiogenic therapies.

PMID- 24733741
TI  - Endothelial cell responses in terms of adhesion, proliferation, and morphology to
      stiffness of polydimethylsiloxane elastomer substrates.
AB  - Extracellular environments can regulate cell behavior because cells can actively
      sense their mechanical environments. This study evaluated the adhesion,
      proliferation and morphology of endothelial cells on polydimethylsiloxane
      (PDMS)/alumina (Al2 O3 ) composites and pure PDMS. The substrates were prepared
      from pure PDMS and its composites with 2.5, 5, 7.5, and 10 wt % Al2 O3 at a
      curing temperature of 50 degrees C for 4 h. The substrates were then
      characterized by mechanical, structural, and morphological analyses. The cell
      adhesion, proliferation, and morphology of cultured bovine aortic endothelial
      (BAEC) cells on substrate materials were evaluated by using resazurin assay and
      1,1'-dioctadecyl-1,3,3,3',3'-tetramethylindocarbocyanine perchlorate-acetylated
      LDL (Dil-Ac-LDL) cell staining, respectively. The composites (PDMS/2.5, 5, 7.5,
      and 10 wt % Al2 O3 ) exhibited higher stiffness than the pure PDMS substrate. The
      results also revealed that stiffer substrates promoted endothelial cell adhesion
      and proliferation and also induced spread morphology in the endothelial cells
      compared with lesser stiff substrates. Statistical analysis showed that the
      effect of time on cell proliferation depended on stiffness. Therefore, this study
      concludes that the addition of different Al2 O3 percentages to PDMS elevated
      substrate stiffness which in turn increased endothelial cell adhesion and
      proliferation significantly and induced spindle shape morphology in endothelial
      cells.

PMID- 24733740
TI  - Chronic rhinosinusitis without nasal polyps is associated with increased
      expression of trefoil factor family peptides.
AB  - BACKGROUND: Trefoil factor family (TFF) peptides are mucin-associated secretory
      products that are produced in the airways and gastrointestinal tract. These
      peptides appear to play an important role in mucosal healing and epithelial
      protection and are overexpressed in chronically inflamed gastrointestinal
      tissues. We hypothesize that TFF peptides may also be differentially expressed in
      the sinonasal tissue of patients with and without chronic rhinosinusitis (CRS).
      METHODS: Ethmoid sinus tissue was obtained from patients with CRS without nasal
      polyps (CRSsNP) (n = 12), CRS with nasal polyps (CRSwNP) (n = 12), and
      nondiseased controls (n = 7). Messenger RNA (mRNA) and protein were extracted
      from samples and expression of TFF1, TFF2, and TFF3 were assessed using
      quantitative real-time polymerase chain reaction qRT-PCR and Western blots,
      respectively. Tissue localization of TFF expression was confirmed using
      immunohistochemistry. RESULTS: TFF1 and TFF3 were both highly expressed in
      sinonasal tissue, while TFF2 was expressed at near-undetectable levels. CRSsNP
      tissue had a statistically significant increase in the expression of both TFF1
      and TFF3. No difference in TFF expression was found between control and CRSwNP
      patients. CONCLUSION: TFF1 and TFF3 are overexpressed in CRSsNP. The role of TFF
      peptides in mucosal protection and repair suggests a possible important
      physiologic role in maintaining the sinonasal epithelial barrier and modulating
      innate immunity in the sinonasal tract.

PMID- 24733742
TI  - Inducing bias modulates sensitivity to nonverbal cues of others' pain.
AB  - BACKGROUND: There is ample research to support the existence of bias in the
      perception of others' pain. Both studies involving health-care professionals and
      student surrogate samples have found that, firstly, pain is under-perceived when
      using nonverbal cues to gauge another's suffering and, secondly, that personal
      characteristics of both the viewer and the target (such as gender) can bias pain
      perception, affecting the allocation of help. However, the extant research shows
      conflicts about the direction of the bias that target gender exerts on pain
      perception. Our study aims to address these challenges by examining whether under
      perception of pain can be attenuated or exacerbated with gender primes and how
      target gender affects nonverbal pain perception, in particular. METHODS:
      University students (N = 120) were primed with either masculine, neutral, or
      feminine concepts followed by photos of male and female targets displaying
      various levels of pain and asked to quantify the photographed targets' distress.
      RESULTS: Participants perceived lower target distress when this task was preceded
      by a masculine gender prime, as compared to a neutral or feminine gender prime.
      Pain was underestimated for all targets; however, this underestimation was
      significantly more pronounced for female targets. CONCLUSIONS: These results
      suggest that gender cues may influence the perception of observed pain and, as a
      result, clinical decision making. They also support the conjecture that nonverbal
      pain cues may be under-perceived in women.

PMID- 24733743
TI  - Auto-amplification system for prostaglandin F2alpha in bovine corpus luteum.
AB  - The bovine corpus luteum (CL) is hypothesized to utilize a local auto
      amplification system for prostaglandin (PG) F2alpha production. The objective of
      the present study was to determine if such a PGF2alpha auto-amplification system
      exists in the bovine CL, and if so, which factors regulate it. PGF2alpha
      significantly stimulated intra-luteal PGF2alpha production in all luteal phases,
      but did not affect PGE2 production. The stimulatory effect of exogenous PGF2alpha
      on CL PGF2alpha production was lower at the early luteal phase. Indomethacin, an
      inhibitor of prostaglandin-endoperoxide synthase (PTGS), significantly suppressed
      the PGF2alpha-stimulated PGF2alpha production by luteal tissue, indicating that
      the PGF2alpha in the medium was of luteal origin. Consistent with these secreted
      PGF2alpha profiles, PGF2alpha receptor (PTGFR) protein expression was higher
      during the mid and late luteal phases than at early and developing luteal phases.
      Treatment of cultured bovine luteal cells obtained from the mid-luteal phase with
      PGF2alpha (1 uM) significantly increased the expressions of PTGS2, PGF synthase
      (PGFS), and carbonyl reductase1 (CBR1) at 24 hr post-treatment. Together, these
      results suggest the presence of a local auto-amplification system for PGF2alpha
      mediated by PTGS2, PGFS, and CBR1 in the bovine CL, which may play an important
      role in luteolysis.

PMID- 24733744
TI  - Properties of a 2D fat navigator for prospective image domain correction of
      nodding motion in brain MRI.
AB  - PURPOSE: A two-dimensional fat navigator (FatNav) image is proposed, designed for
      future use as a means of prospective motion correction of head-nodding motion.
      METHODS: The proposed FatNav module comprised a fat-selective excitation,
      followed by an accelerated echo planar imaging readout played out in one central
      sagittal plane. Step-wise motion experiments with different acceleration factors,
      blip polarity, and matrix sizes were performed. The accuracy of motion estimates
      derived from the FatNav data was assessed using water-based, distortion-free,
      spoiled-gradient echo images as the gold standard. The duration of the FatNav
      module was 10 ms to 20 ms. Volunteer data were acquired on a 3T system using an 8
      channel radiofrequency coil. METHODS: It is shown that acceleration factors of R
      = 8 are feasible for FatNav data. Best results are obtained when parallel imaging
      calibration data is matched in terms of both geometric distortions and signal
      content. For head rotations up to about 15 mm and 20 degrees, mean absolute
      errors of the motion estimates using FatNav data were about 0.5 mm and 1 degree.
      CONCLUSION: FatNav is advantageous in that it leaves most of the brain water
      magnetization unaffected and left to the host pulse sequence. Furthermore, high
      acceleration factors are possible with FatNav, which reduces estimation bias and
      the navigator duration.

PMID- 24733745
TI  - A patient with rheumatoid arthritis, cryoglobulinaemia, and an "accidental"
      finding.

PMID- 24733746
TI  - Elongator and SPT4/SPT5 complexes as proxy to study RNA polymerase II transcript
      elongation control of plant development.
AB  - The elongation phase of the RNA polymerase II (RNAPII) transcription process is
      dynamic and regulated. Elongator and SUPPRESSOR OF Ty4 (SPT4)/SPT5 are transcript
      elongation factors that contribute to the regulation of mRNA synthesis by RNA
      polymerase II in the chromatin context. Recently, the Elongator complex
      consisting of six subunits and the SPT4/SPT5 heterodimer were isolated from
      Arabidopsis. Mutant plants affected in the expression of Elongator or SPT4/SPT5
      share various auxin-signaling phenotypes. In line with that observation, auxin
      related genes are prominent among the genes differentially expressed in these
      mutants. Exemplified by Elongator and SPT4/SPT5, we discuss here the role that
      transcript elongation factors may play in the control of plant growth and
      development.

PMID- 24733747
TI  - P2Y1 receptor inhibits GABA transport through a calcium signalling-dependent
      mechanism in rat cortical astrocytes.
AB  - Astrocytes express a variety of purinergic (P2) receptors, involved in astrocytic
      communication through fast increases in [Ca(2+) ]i . Of these, the metabotropic
      ATP receptors (P2Y) regulate cytoplasmic Ca(2+) levels through the PLC-PKC
      pathway. GABA transporters are a substrate for a number of Ca(2+) -related
      kinases, raising the possibility that calcium signalling in astrocytes impact the
      control of extracellular levels of the major inhibitory transmitter in the brain.
      To access this possibility we tested the influence of P2Y receptors upon GABA
      transport into astrocytes. Mature primary cortical astroglial-enriched cultures
      expressed functional P2Y receptors, as evaluated through Ca(2+) imaging, being
      P2Y1 the predominant P2Y receptor subtype. ATP (100 MUM, for 1 min) caused an
      inhibition of GABA transport through either GAT-1 or GAT-3 transporters,
      decreasing the Vmax kinetic constant. ATP-induced inhibition of GATs activity was
      still evident in the presence of adenosine deaminase, precluding an adenosine
      mediated effect. This, was mimicked by a specific agonist for the P2Y1,12,13
      receptor (2-MeSADP). The effect of 2-MeSADP on GABA transport was blocked by the
      P2 (PPADS) and P2Y1 selective (MRS2179) receptor antagonists, as well as by the
      PLC inhibitor (U73122). 2-MeSADP failed to inhibit GABA transport in astrocytes
      where intracellular calcium had been chelated (BAPTA-AM) or where calcium stores
      were depleted (alpha-cyclopiazonic acid, CPA). In conclusion, P2Y1 receptors in
      astrocytes inhibit GABA transport through a mechanism dependent of P2Y1 -mediated
      calcium signalling, suggesting that astrocytic calcium signalling, which occurs
      as a consequence of neuronal firing, may operate a negative feedback loop to
      enhance extracellular levels of GABA.

PMID- 24733749
TI  - Preparation of animal polysaccharides nanofibers by electrospinning and their
      potential biomedical applications.
AB  - Animal polysaccharides belong to a class of biological macromolecules. They are
      natural biopolymers with numerous advantages for biomedical applications, such as
      biocompatibility, biodegradability, non-antigenicity and non-toxicity.
      Electrospinning is a versatile and facile technique which can produce continuous
      fibers with nanoscale from a wide range of natural and synthetic polymers. The
      review aims to provide an up-to-date overview of the preparation of animal
      polysaccharides nanofibers by electrospinning and their potential biomedical
      applications such as tissue engineering, wound healing, and drug delivery.
      Various animal polysaccharides including chitin and chitosan (CS), hyaluronic
      acid (HA), heparin and heparan sulfate (HS), and chondroitin sulfate (ChS), are
      discussed. The challenges and some useful strategies in electrospinning of animal
      polysaccharides also are summarized. In addition, future study of animal
      polysaccharides nanofibers by electrospinning is proposed.

PMID- 24733748
TI  - Porcine nasal epithelial cultures for studies of cystic fibrosis sinusitis.
AB  - BACKGROUND: Transgenic cystic fibrosis (CF) murine models do not develop
      spontaneous lung or sinus disease, 2 major causes of morbidity in human CF
      patients. Because of these limitations, transgenic cystic fibrosis transmembrane
      conductance regulator (CFTR)(-/-) pigs have been developed and are currently
      being characterized. These CF animal models have phenotypes closely resembling
      that of human CF subjects. The objectives of the current study were to develop
      primary porcine nasal epithelial (PNE) cultures and evaluate their usefulness as
      a means to investigate sinonasal transepithelial transport and CFTR function.
      METHODS: PNE derived from the septum or turbinates of CFTR(+/+) and CFTR(-/-)
      pigs were cultured at an air-liquid interface to confluence and full
      differentiation. Epithelial monolayers were mounted in Ussing chambers to
      investigate pharmacologic manipulation of ion transport. Ciliary beat frequency
      (CBF) and scanning electron microscopy of monolayers were used to indicate degree
      of ciliation and cell differentiation. RESULTS: Stimulation of CFTR-mediated
      anion transport (DeltaIsc in MUA/cm(2) ) was significantly greater in epithelia
      derived from the septum when compared to turbinates (33.04 +/- 1.17 vs 18.9 +/-
      0.73; p < 0.05). Cyclic adenosine monophosphate (cAMP)-activated Cl(-) secretion
      was absent in CFTR(-/-) and present in CFTR(+/+) epithelia. Calcium-activated Cl(
      ) (CaCC) secretion was increased in CF; however, overall Cl(-) transport through
      CaCCs was very low. Degree of ciliation (90%) and CBF were similar between
      groups. CONCLUSION: Septal PNE exhibit a robust ion transport phenotype and
      indicate CFTR(-/-) sinus disease could be attributable to diminished alternative
      pathways for Cl(-) transport. Overall, PNE have similarities to human respiratory
      epithelia not demonstrated in murine cells and represent useful in vitro models
      for studying CF sinus disease.

PMID- 24733750
TI  - Angiotensin (1-7) prevents angiotensin II-induced nociceptive behaviour via
      inhibition of p38 MAPK phosphorylation mediated through spinal Mas receptors in
      mice.
AB  - BACKGROUND: We have recently demonstrated that intrathecal (i.t.) administration
      of angiotensin II (Ang II) induces nociceptive behaviour in mice accompanied by a
      phosphorylation of p38 mitogen-activated protein kinase (MAPK) mediated through
      Ang II type 1 (AT1 ) receptors. The N-terminal fragment of Ang II, Ang (1-7),
      plays a pivotal role in counterbalancing many of the well-established actions
      induced by Ang II. However, the role of Ang (1-7) in spinal nociceptive
      transmission remains unclear. Therefore, we examined whether i.t. administration
      of Ang (1-7) can inhibit the Ang II-induced nociceptive behaviour in mice.
      METHODS: In the behavioural experiments, the accumulated response time of
      nociceptive behaviour consisting of scratching, biting and licking in conscious
      mice was determined during a 25-min period starting after i.t. injection. The
      distribution and localization of AT1 or Mas receptors were analysed using a
      MapAnalyzer and confocal microscope, respectively. Phosphorylation of p38 MAPK in
      the dorsal spinal cord was measured by Western blotting. RESULTS: The nociceptive
      behaviour induced by Ang II was dose-dependently inhibited by the co
      administration of Ang (1-7). The inhibitory effect of Ang (1-7) was reversed by
      the co-administration of A779, a Mas receptor antagonist. Western blot analysis
      showed that the increase in spinal p38 MAPK phosphorylation following the i.t.
      administration of Ang II was also inhibited by Ang (1-7), and the Ang (1-7)
      induced-inhibition was prevented by A779. CONCLUSIONS: Our data show that the
      i.t. administration of Ang (1-7) attenuates an Ang II-induced nociceptive
      behaviour and is accompanied by the inhibition of p38 MAPK phosphorylation
      mediated through Mas receptors.

PMID- 24733751
TI  - What Type of Social Support Influences Self-Reported Physical and Mental Health
      Among Older Women?
AB  - OBJECTIVE: We examined which types of social support were associated with older
      women's self-report of physical and mental health and whether the effects of
      social support were moderated by race/ethnicity. METHOD: Women completed a health
      behavior survey that included the Medical Outcomes Study-Short Form-12 (MOS SF
      12). Single race/ethnic group regressions examined whether different types of
      social support were related to health. We also examined Pratt's relative
      importance measures. RESULTS: Emotional support had the strongest effect on both
      physical and mental health, explaining the highest amount of variation, except
      among African Americans. Race/ethnicity moderated the association of
      informational support for Asian women's reports of their mental health.
      DISCUSSION: For clinicians, assessing individuals' emotional support is important
      for maintaining or increasing physical and mental health. Clinicians can also
      assess Asian women's stress, providing informational support accordingly as too
      much information could be detrimental to their health. For researchers, the
      inclusion of emotional support items is the most important.

PMID- 24733752
TI  - Religious Attendance and Biological Functioning: A Multiple Specification
      Approach.
AB  - OBJECTIVE: This study explores the role of religious attendance across a wide
      range of biological markers. METHOD: The data are drawn from the National Social
      Life, Health, and Aging Project to assess continuous and categorical biomarker
      specifications. RESULTS: Across specifications, higher levels of attendance are
      associated with lower levels of pulse rate and overall allostatic load. Depending
      on the specification, higher levels of attendance are also associated with lower
      levels of body mass, diastolic blood pressure, C-reactive protein, and Epstein
      Barr virus. Attendance is unrelated to dehydroepiandrosterone, systolic blood
      pressure, and glycosylated hemoglobin across specifications. DISCUSSION: The
      study confirms that religious attendance is associated with healthier biological
      functioning in later life. Additional research is needed to verify these patterns
      with other data sources and to test viable mediators of the association between
      religious attendance and biological risk.

PMID- 24733753
TI  - Generating a detailed protein profile of Fasciola hepatica during the chronic
      stage of infection in cattle.
AB  - Fasciola hepatica is a trematode helminth causing a damaging disease,
      fasciolosis, in ruminants and humans. Comprehensive proteomic studies broaden our
      knowledge of the parasite's protein profile, and provide new insights into the
      development of more effective strategies to deal with fasciolosis. The objective
      of this study was to generate a comprehensive profile of F. hepatica proteins
      expressed during the chronic stage of infection in cattle by building on previous
      efforts in this area. The approach included an improved sample preparation
      procedure for surface and internal layers of the parasite, the application of
      nano-UPLC-ESI-qTOF-MS (nano-ultra-performance LC and ESI quadrupole TOF MS)
      integrated with different acquisition methods and in silico database search
      against various protein databases and a transcript database including a new
      assembly of publically available EST. Of a total of 776 identified proteins, 206
      and 332 were specific to the surface and internal layers of the parasite,
      respectively. Furthermore, 238 proteins were common to both layers, with
      comparative differences of 172 proteins detected. Specific proteins not
      previously identified in F. hepatica, but shown to be immunomodulatory or
      potential drug targets for other parasites, are discussed. 

PMID- 24733754
TI  - Assessment of diffusion tensor MR imaging (DTI) in liver fibrosis with minimal
      confounding effect of hepatic steatosis.
AB  - PURPOSE: Given the potential confounding effect of fat on apparent diffusion
      coefficient (ADC) in the liver, we have assessed diffusion tensor imaging in
      liver fibrosis with minimal effect of fat on ADC and fractional anisotropy (FA).
      METHODS: Thirty-six mice were used, among which 20 mice were CCl4 treated for
      fibrosis induction. Diffusion tensor imaging was performed at 9.4T using a spin
      echo diffusion tensor imaging sequence with six gradient directions. Hepatic fat
      fraction obtained by MR spectroscopy was used as hepatic fat content. Fibrosis
      scores were obtained from histopathology. RESULTS: The hepatic fat fractions of
      the two animal groups were below 5.5% and not different (5.3 +/- 1.5 vs. 4.6 +/-
      1.1%; P = 0.115). Fibrosis scores were higher in CCl4 -treated mice (0.0 +/- 0.0
      vs. 2.1 +/- 0.7; P < 0.001). Nonetheless, there was no difference in ADC between
      the two groups (0.711 +/- 0.068 * 10(-3) vs. 0.718 +/- 0.095 * 10(-3) mm(2) s(-1)
      ; P = 0.911). The treated group had a lower FA than control (0.552 +/- 0.050 vs.
      0.586 +/- 0.013; P = 0.023). ADC was not correlated with hepatic fat fraction and
      fibrosis. FA was correlated with hepatic fat fraction (r = 0.418, P = 0.011) and
      fibrosis (r = -0.411, P = 0.012). CONCLUSION: FA may be more sensitive to mild-to
      moderate liver fibrosis than ADC. In addition to ADC, FA may also be sensitive to
      hepatic fat content, and therefore need careful interpretation in liver fibrosis
      with concomitant fatty liver.

PMID- 24733755
TI  - Some local authorities are funding public health programmes.

PMID- 24733757
TI  - Recombinant TAT-gelonin fusion toxin: synthesis and characterization of
      heparin/protamine-regulated cell transduction.
AB  - Protein toxins, such as gelonin, are highly desirable anti-cancer drug candidates
      due to their unparalleled potency and repetitive reaction mechanism in inhibiting
      protein translation. However, for its potential application in cancer therapy,
      there remains the cell membrane barrier that allows permeation of only small
      molecules, which must be overcome. To address this challenge, we conjugated
      gelonin with a protein transduction domain (PTD), the TAT peptide, via genetic
      recombination. The chimeric TAT-gelonin fusion protein (TAT-Gel) retained
      equipotent N-glycosidase activity yet displayed greater cell uptake than
      unmodified recombinant gelonin (rGel), thereby yielding a significantly augmented
      cytotoxic activity. Remarkably, TAT-Gel displayed up to 177-fold lower IC50 (avg.
      54.3 nM) than rGel (avg. IC50 : 3640 nM) in tested cell lines. This enhanced
      cytotoxicity, however, also raised potential toxicity concerns due to the non
      selectivity of PTD in its mediated cell transduction. To solve this problem, we
      investigated the plausibility of regulating the cell transduction of TAT-Gel via
      a reversible masking using heparin and protamine. Here, we demonstrated, both in
      vitro and in vivo, that the cell transduction of TAT-Gel can be completely curbed
      with heparin and yet this heparin block can be efficiently reversed by the
      addition of protamine. This reversible tight regulation of the cell transduction
      of TAT-Gel by heparin and protamine sheds light of possible application of TAT
      Gel in achieving a highly effective yet safe drug therapy for the treatment of
      tumors.

PMID- 24733756
TI  - Astrocytic transforming growth factor-beta signaling reduces subacute
      neuroinflammation after stroke in mice.
AB  - Astrocytes limit inflammation after CNS injury, at least partially by physically
      containing it within an astrocytic scar at the injury border. We report here that
      astrocytic transforming growth factor-beta (TGFbeta) signaling is a second,
      distinct mechanism that astrocytes utilize to limit neuroinflammation. TGFbetas
      are anti-inflammatory and neuroprotective cytokines that are upregulated
      subacutely after stroke, during a clinically accessible time window. We have
      previously demonstrated that TGFbetas signal to astrocytes, neurons and microglia
      in the stroke border days after stroke. To investigate whether TGFbeta affects
      astrocyte immunoregulatory functions, we engineered "Ast-Tbr2DN" mice where
      TGFbeta signaling is inhibited specifically in astrocytes. Despite having a
      similar infarct size to wildtype controls, Ast-Tbr2DN mice exhibited
      significantly more neuroinflammation during the subacute period after distal
      middle cerebral occlusion (dMCAO) stroke. The peri-infarct cortex of Ast-Tbr2DN
      mice contained over 60% more activated CD11b(+) monocytic cells and twice as much
      immunostaining for the activated microglia and macrophage marker CD68 than
      controls. Astrocytic scarring was not altered in Ast-Tbr2DN mice. However, Ast
      Tbr2DN mice were unable to upregulate TGF-beta1 and its activator thrombospondin
      1 2 days after dMCAO. As a result, the normal upregulation of peri-infarct
      TGFbeta signaling was blunted in Ast-Tbr2DN mice. In this setting of lower
      TGFbeta signaling and excessive neuroinflammation, we observed worse motor
      outcomes and late infarct expansion after photothrombotic motor cortex stroke.
      Taken together, these data demonstrate that TGFbeta signaling is a molecular
      mechanism by which astrocytes limit neuroinflammation, activate TGFbeta in the
      peri-infarct cortex and preserve brain function during the subacute period after
      stroke.

PMID- 24733758
TI  - Pain threshold and sleep quality in women with endometriosis.
AB  - BACKGROUND: Pain is a common complaint in women with endometriosis and can be
      influenced by many variables, including sleep disorders; however, no data are
      available on the sleep quality of women with endometriosis or on the correlation
      between sleep quality and pain. METHODS: The 510 volunteers included in this
      study were divided into two groups: 257 women with a laparoscopic and
      histopathological diagnosis of endometriosis and 253 women with no history of
      endometriosis and no endometriosis-related symptoms. The volunteers answered two
      questionnaires: the Post-Sleep Inventory to evaluate sleep quality and the
      International Physical Activity Questionnaire to assess their level of physical
      activity. Pain was evaluated using a visual analogue scale (VAS) and women were
      also submitted to a physical examination, during which their pain threshold was
      assessed at 20 different body sites. RESULTS: Sleep quality was significantly
      poorer in women with endometriosis compared to women without the disease. The
      pain threshold was significantly lower in the greater trochanter and abdomen in
      women with endometriosis when compared to women without the disease; however,
      there was no difference in VAS pain score between the groups. The higher the VAS
      pain score, the lower the Post-Sleep Inventory score. Additionally, there was a
      significant positive correlation between the pain threshold at some body sites
      and sleep quality. CONCLUSIONS: Sleep quality was poorer and the pain threshold
      at certain body sites was lower in the group of women with endometriosis.

PMID- 24733759
TI  - The overexpression of a single oncogene (ERBB2/HER2) alters the proteomic
      landscape of extracellular vesicles.
AB  - ERBB2/HER2 amplification activates signaling cascades that lead to a tumor cell
      phenotype. However, despite its remarkable importance in oncology, the
      consequences of HER2 amplification over the extracellular vesicles (EVs) content
      have not yet been investigated. Here, we isolated EVs secreted by HB4a, a mammary
      luminal epithelial cell line and C5.2, its HER2-overexpressing clone. We isolated
      two EV sets (20 and 100 K) by ultracentrifugation and used electron microscopy
      and nanoparticle tracking analysis for their morphological characterization. We
      employed GeLC-MS/MS combined with isotope-coded protein labeling to evaluate cell
      derived proteins and LC-MS/MS label free spectral counting to quantify the EVs
      proteome. We found higher HER2 levels in both C5.2-derived EVs when compared with
      C5.2 cells, suggesting its preferential shuttling. Proteins capable of inducing
      malignant transformation are enriched in both C5.2 EV subsets, including two HER2
      related proteins involved in cell motility and invasion, cofilin and CD44.
      MetaCoreTM analysis indicated an enrichment of cell adhesion and cytoskeleton
      remodeling pathways in C5.2 EVs, as well as proteins related to HER2 signaling,
      such as sphingosine-1-phosphate pathway. Together, our data indicate that in
      terms of protein content, distinct vesicle sets reinforce and complement each
      other. Our results also suggest that HER2-upregulated proteins from EVs may be
      relevant for cellular malignancy and can be potential biomarkers for HER2(+)
      cancer patients. 

PMID- 24733760
TI  - Atrophying pityriasis versicolor.

PMID- 24733761
TI  - Inefficient health care costs lives: CIHI.

PMID- 24733762
TI  - Midwifery to be offered in Newfoundland and Labrador.

PMID- 24733763
TI  - Time to rein in the "Wild West" of medical apps.

PMID- 24733764
TI  - Decline in early elective deliveries across the United States.

PMID- 24733765
TI  - Confidentiality concerns delay UK patient data system.

PMID- 24733767
TI  - Brief interventions for substance use in adolescents: still promising, still
      unproven.

PMID- 24733768
TI  - Artificial trans fatty acids do not belong in our food.

PMID- 24733769
TI  - Fever and rash in a woman returning from the Caribbean.

PMID- 24733770
TI  - Case management for blood pressure and lipid level control after minor stroke:
      PREVENTION randomized controlled trial.
AB  - BACKGROUND: Optimization of systolic blood pressure and lipid levels are
      essential for secondary prevention after ischemic stroke, but there are
      substantial gaps in care, which could be addressed by nurse- or pharmacist-led
      care. We compared 2 types of case management (active prescribing by pharmacists
      or nurse-led screening and feedback to primary care physicians) in addition to
      usual care. METHODS: We performed a prospective randomized controlled trial
      involving adults with recent minor ischemic stroke or transient ischemic attack
      whose systolic blood pressure or lipid levels were above guideline targets.
      Participants in both groups had a monthly visit for 6 months with either a nurse
      or pharmacist. Nurses measured cardiovascular risk factors, counselled patients
      and faxed results to primary care physicians (active control). Pharmacists did
      all of the above as well as prescribed according to treatment algorithms
      (intervention). RESULTS: Most of the 279 study participants (mean age 67.6 yr,
      mean systolic blood pressure 134 mm Hg, mean low-density lipoprotein [LDL]
      cholesterol 3.23 mmol/L) were already receiving treatment at baseline
      (antihypertensives: 78.1%; statins: 84.6%), but none met guideline targets
      (systolic blood pressure <= 140 mm Hg, fasting LDL cholesterol <= 2.0 mmol/L).
      Substantial improvements were observed in both groups after 6 months: 43.4% of
      participants in the pharmacist case manager group met both systolic blood
      pressure and LDL guideline targets compared with 30.9% in the nurse-led group
      (12.5% absolute difference; number needed to treat = 8, p = 0.03).
      INTERPRETATION: Compared with nurse-led case management (risk factor evaluation,
      counselling and feedback to primary care providers), active case management by
      pharmacists substantially improved risk factor control at 6 months among patients
      who had experienced a stroke. TRIAL REGISTRATION: ClinicalTrials.gov, no.
      NCT00931788.

PMID- 24733772
TI  - Neuronal release and successful astrocyte uptake of aminoacidergic
      neurotransmitters after spinal cord injury in lampreys.
AB  - In contrast to mammals, the spinal cord of lampreys spontaneously recovers from a
      complete spinal cord injury (SCI). Understanding the differences between lampreys
      and mammals in their response to SCI could provide valuable information to
      propose new therapies. Unique properties of the astrocytes of lampreys probably
      contribute to the success of spinal cord regeneration. The main aim of our study
      was to investigate, in the sea lamprey, the release of aminoacidergic
      neurotransmitters and the subsequent astrocyte uptake of these neurotransmitters
      during the first week following a complete SCI by detecting glutamate, GABA,
      glycine, Hu and cytokeratin immunoreactivities. This is the first time that
      aminoacidergic neurotransmitter release from neurons and the subsequent
      astrocytic response after SCI are analysed by immunocytochemistry in any
      vertebrate. Spinal injury caused the immediate loss of glutamate, GABA and
      glycine immunoreactivities in neurons close to the lesion site (except for the
      cerebrospinal fluid-contacting GABA cells). Only after SCI, astrocytes showed
      glutamate, GABA and glycine immunoreactivity. Treatment with an inhibitor of
      glutamate transporters (DL-TBOA) showed that neuronal glutamate was actively
      transported into astrocytes after SCI. Moreover, after SCI, a massive
      accumulation of inhibitory neurotransmitters around some reticulospinal axons was
      observed. Presence of GABA accumulation significantly correlated with a higher
      survival ability of these neurons. Our data show that, in contrast to mammals,
      astrocytes of lampreys have a high capacity to actively uptake glutamate after
      SCI. GABA may play a protective role that could explain the higher regenerative
      and survival ability of specific descending neurons of lampreys.

PMID- 24733773
TI  - Injectable colloidal gold in a sucrose acetate isobutyrate gelating matrix with
      potential use in radiation therapy.
AB  - External beam radiation therapy relies on the ability to deliver high radiation
      doses to tumor cells with minimal exposure to surrounding healthy tissue.
      Advanced irradiation techniques, including image-guided radiation therapy (IGRT),
      rely on the ability to locate tumors to optimize the therapeutic benefit of these
      techniques. Today, radiopaque fiducial tissue markers are placed in or around
      tumors, for example, in prostate cancer patients to enhance the precision of
      daily and/or real-time IGRT. A liquid injectable fiducial marker (nanogel) is
      developed based on PEGylated gold nanoparticles and sucrose acetate isobutyrate
      (SAIB) with improved properties compared to current solid fiducial markers. The
      developed nanogel is investigated in vitro and subsequently evaluated in vivo in
      immunocompetent NMRI mice. The nanogel shows high CT-contrast and excellent
      stability in vivo over a period of 12 weeks. The nanogel is found to be
      biocompatible and well tolerated. No induction of the inflammatory cytokines INF
      gamma, IL-6, or TNF-alpha is observed throughout the study period. The developed
      nanogel seems to be a safe injectable fiducial marker ideally suited for IGRT
      that may further enhance the effect of radiation. 

PMID- 24733774
TI  - Quantitative regulation of bone-mimetic, oriented collagen/apatite matrix
      structure depends on the degree of osteoblast alignment on oriented collagen
      substrates.
AB  - Bone tissue has a specific anisotropic morphology derived from collagen fiber
      alignment and the related apatite crystal orientation as a bone quality index.
      However, the precise mechanism of cellular regulation of the crystallographic
      orientation of apatite has not been clarified. In this study, anisotropic
      construction of cell-produced mineralized matrix in vitro was established by
      initiating organized cellular alignment and subsequent oriented bone-like matrix
      (collagen/apatite) production. The oriented collagen substrates with three
      anisotropic levels were prepared by a hydrodynamic method. Primary osteoblasts
      were cultured on the fabricated substrates until mineralized matrix formation is
      confirmed. Osteoblast alignment was successfully regulated by the level of
      substrate collagen orientation, with preferential alignment along the direction
      of the collagen fibers. Notably, both fibrous orientation of newly synthesized
      collagen matrix and c-axis of produced apatite crystals showed preferential
      orientation along the cell direction. Because the degree of anisotropy of the
      deposited apatite crystals showed dependency on the directional distribution of
      osteoblasts cultured on the oriented collagen substrates, the cell orientation
      determines the crystallographic anisotropy of produced apatite crystals. To the
      best of our knowledge, this is the first report demonstrating that bone tissue
      anisotropy, even the alignment of apatite crystals, is controllable by varying
      the degree of osteoblast alignment via regulating the level of substrate
      orientation.

PMID- 24733775
TI  - The effects of dimethyl 3,3'-dithiobispropionimidate di-hydrochloride cross
      linking of collagen and gelatin coating on porous spherical biphasic calcium
      phosphate granules.
AB  - Collagen- and gelatin-coated porous spherical granule was prepared by slurry
      dripping process using biphasic calcium phosphate powder. The coating was
      stabilized by cross-linking with dimethyl 3,3'-dithiobispropionimidate di
      hydrogenchloride (DTBP). Afer DTBP cross-linking, the nanostructure of collagen-
      and gelatin-coated surfaces was changed from smooth to fibrous and net-like
      structure. Excellent cross-linking of the coating was seen as indicated by the
      differential scanning calorimetry thermogram and the Fourier transform infrared
      spectroscopy spectra. After cross-linking the relative intensities of the Fourier
      transform infrared spectroscopy peaks were decreased and amide bands were shifted
      to the left. The interaction of gelatin with DTBP cross-linking agent was
      stronger than that with collagen according to differential scanning calorimetry
      and Fourier transform infrared spectroscopy results. The compressive strength of
      the granular bone substitutes increased significantly after the coating process
      and gelatin coated biphasic calcium phosphate granules showed highest value at
      3.68 MPa after cross-linking. Porosity was greater than 63% and did not change
      significantly with coating. Biocompatibility investigation by in vitro and in
      vivo showed that the coating improved the cell proliferation marginally. However,
      the cross-linking process did not jeopardize the excellent biocompatibility of
      collagen and gelatin. The in vivo study confirms better bone formation behavior
      of the cross-linked gelatin and collagen coated samples investigated for 8 weeks
      in vivo.

PMID- 24733776
TI  - Fiber-reinforced hydrogel scaffolds for heart valve tissue engineering.
AB  - Heart valve-related disorders are among the major causes of death worldwide.
      Although prosthetic valves are widely used to treat this pathology, current
      prosthetic grafts cannot grow with the patient while maintaining normal valve
      mechanical and hemodynamic properties. Tissue engineering may provide a possible
      solution to this issue through using biodegradable scaffolds and patients' own
      cells. Despite their similarity to heart valve tissue, most hydrogel scaffolds
      are not mechanically suitable for the dynamic stresses of the heart valve
      microenvironment. In this study, we integrated electrospun poly(glycerol
      sebacate) (PGS)-poly(E-caprolactone) (PCL) microfiber scaffolds, which possess
      enhanced mechanical properties for heart valve engineering, within a hybrid
      hydrogel made from methacrylated hyaluronic acid and methacrylated gelatin. Sheep
      mitral valvular interstitial cells were encapsulated in the hydrogel and
      evaluated in hydrogel-only, PGS-PCL scaffold-only, and composite scaffold
      conditions. Although the cellular viability and metabolic activity were similar
      among all scaffold types, the presence of the hydrogel improved the three
      dimensional distribution of mitral valvular interstitial cells. As seen by
      similar values in both the Young's modulus and the ultimate tensile strength
      between the PGS-PCL scaffolds and the composites, microfibrous scaffolds
      preserved their mechanical properties in the presence of the hydrogels. Compared
      to electrospun or hydrogel scaffolds alone, this combined system may provide a
      more suitable three-dimensional structure for generating scaffolds for heart
      valve tissue engineering. 

PMID- 24733777
TI  - Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue of the
      salivary glands: a population-based study from 1994 to 2009.
AB  - BACKGROUND: Extranodal marginal zone lymphoma of mucosa-associated lymphoid
      tissue (MALT lymphoma) arising from the salivary glands is rare. METHODS: Five
      hundred seven cases were available for frequency/incidence analysis, and 712 for
      relative survival and regression analysis in the Surveillance Epidemiology and
      End Results (SEER) database. RESULTS: Of the total patients, 72.98% were women,
      80.47% were white, and 74.75% were >=50 years old. The parotid gland was involved
      in 80.87% of cases. Ann Arbor stage at diagnosis was 53.85% IE, 18.54% IIE, and
      10.06% IIIE/IV. Overall, 15-year relative survival was 78.40%. Relative survival
      was worst among blacks and those with advanced-stage disease. No difference was
      noted between those treated with surgery, radiation, or both. Statistically
      significant poor prognosticators included black race (hazard ratio [HR], 2.3961;
      95% confidence interval [CI], 1.54-3.72; p = .0001) and stage IIIE/IV (HR,
      2.3677; 95%CI, 1.36-4.11; p = .0022). CONCLUSION: Early-stage salivary gland MALT
      lymphoma disease may be amenable to unimodality treatment. Even patients with
      advanced disease have relatively high survivals.

PMID- 24733778
TI  - Adolescent Risperidone treatment alters protein expression associated with
      protein trafficking and cellular metabolism in the adult rat prefrontal cortex.
AB  - The prefrontal cortex (PFC) is associated with mental health illnesses including
      schizophrenia, depression, bipolar disorder, and autism spectrum disorders. It
      richly expresses neuroreceptors which are the target for antipsychotics. However,
      as the precise mechanism of action of antipsychotic medications is not known,
      proteomic studies of the effects of antipsychotic drugs on the brain are
      warranted. In the current study, we aimed to characterize protein expression in
      the adult rodent PFC (n = 5 per group) following low-dose treatment with
      Risperidone or saline in adolescence (postnatal days 34-47). The PFC was examined
      by triplicate 1 h runs of label-free LC-MS/MS. The raw mass spectral data were
      analyzed with the MaxQuant(TM) software. Statistical analysis was carried out
      using SAS(r) Version 9.1. Pathway and functional analysis was performed with
      IngenuityPathway Analysis and in the Database for Annotation, Visualization and
      Integrated Discovery (DAVID), respectively, the most implicated pathways were
      found to be related to mitochondrial function, protein trafficking, and the
      cytoskeleton. This report adds to the current repertoire of data available
      concerning the effects of antipsychotic drugs on the brain and sheds light on
      their biological mechanisms. The MS data have been deposited with the
      ProteomeXchange Consortium with dataset identifier PXD000480. 

PMID- 24733779
TI  - Lipase-catalyzed kinetic resolution of (+/-)-1-(2-furyl) ethanol in nonaqueous
      media.
AB  - S-1-(2-Furyl) ethanol serves as an important chiral building block for the
      preparation of various natural products, fine chemicals, and is widely used in
      the chemical and pharmaceutical industries. In this work, lipase-catalyzed
      kinetic resolution of (R/S)-1-(2-furyl) ethanol using different acyl donors was
      investigated. Vinyl esters are good acyl donors vis-a-vis alkyl esters for
      kinetic resolution. Among them, vinyl acetate was found to be the best acyl
      donor. Different immobilized lipases such as Rhizomucor miehei lipase,
      Thermomyces lanuginosus lipase, and Candida antarctica lipase B were evaluated
      for this reaction, among which C. antarctica lipase B, immobilized on acrylic
      resin (Novozym 435), was found to be the best catalyst in n-heptane as solvent.
      The effect of various parameters was studied in a systematic manner. Maximum
      conversion of 47% and enantiomeric excess of the substrate (ees ) of 89% were
      obtained in 2 h using 5 mg of enzyme loading with an equimolar ratio of alcohol
      to vinyl acetate at 60  degrees C at a speed of 300 rpm in a batch reactor. From
      the analysis of progress curve and initial rate data, it was concluded that the
      reaction followed the ordered bi-bi mechanism with dead-end ester inhibition.
      Kinetic parameters were obtained by using nonlinear regression. This process is
      more economical, green, and easily scalable than the chemical processes.

PMID- 24733781
TI  - Aromatherapy hand massage for older adults with chronic pain living in long-term
      care.
AB  - PURPOSE: Older adults living in long-term care experience high rates of chronic
      pain. Concerns with pharmacologic management have spurred alternative approaches.
      The purpose of this study was to examine a nursing intervention for older adults
      with chronic pain. DESIGN: This prospective, randomized control trial compared
      the effect of aromatherapy M technique hand massage, M technique without
      aromatherapy, and nurse presence on chronic pain. Chronic pain was measured with
      the Geriatric Multidimensional Pain and Illness Inventory factors, pain and
      suffering, life interference, and emotional distress and the Iowa Pain
      Thermometer, a pain intensity scale. METHOD: Three groups of 39 to 40
      participants recruited from seven long-term care facilities participated twice
      weekly for 4 weeks. Analysis included multivariate analysis of variance and
      analysis of variance. FINDINGS: Participants experienced decreased levels of
      chronic pain intensity. Group membership had a significant effect on the
      Geriatric Multidimensional Pain Inventory Pain and Suffering scores; Iowa Pain
      Thermometer scores differed significantly within groups. CONCLUSIONS: M technique
      hand massage with or without aromatherapy significantly decreased chronic pain
      intensity compared to nurse presence visits. M technique hand massage is a safe,
      simple, but effective intervention. Caregivers using it could improve chronic
      pain management in this population.

PMID- 24733780
TI  - Lithium-end-capped polylactide thin films influence osteoblast progenitor cell
      differentiation and mineralization.
AB  - End-capping by covalently binding functional groups to the ends of polymer chains
      offers potential advantages for tissue engineering scaffolds, but the ability of
      such polymers to influence cell behavior has not been studied. As a
      demonstration, polylactide (PLA) was end-capped with lithium carboxylate ionic
      groups (hPLA13kLi) and evaluated. Thin films of the hPLA13kLi and PLA homopolymer
      were prepared with and without surface texturing. Murine osteoblast progenitor
      cells from collagen 1alpha1 transgenic reporter mice were used to assess cell
      attachment, proliferation, differentiation, and mineralization. Measurement of
      green fluorescent protein expressed by these cells and xylenol orange staining
      for mineral allowed quantitative analysis. The hPLA13kLi was biologically active,
      increasing initial cell attachment and enhancing differentiation, while reducing
      proliferation and strongly suppressing mineralization, relative to PLA. These
      effects of bound lithium ions (Li(+) ) had not been previously reported, and were
      generally consistent with the literature on soluble additions of lithium. The
      surface texturing generated here did not influence cell behavior. These results
      demonstrate that end-capping could be a useful approach in scaffold design, where
      a wide range of biologically active groups could be employed, while likely
      retaining the desirable characteristics associated with the unaltered homopolymer
      backbone.

PMID- 24733784
TI  - A smart drug delivery system from charge-conversion polymer-drug conjugate for
      enhancing tumor therapy and tunable drug release.
AB  - A smart drug delivery system is prepared by citraconylated polyaspartic acid
      (PASP) derivate-drug conjugate. The conjugate contains two pH-sensitive groups:
      citraconic amide and hydrazone linker. Citraconic amide group can enhance tumor
      therapy efficiency by the extracellular pH-sensitive charge-conversion property.
      Hydrazone linker between polymer and drug can cleave efficiently in the
      intracellular pH environment. The resulting conjugate shows dual-pH sensitive
      properties: extracellular pH-triggered enhanced tumor targeting and intracellular
      pH-triggered drug release. The results of physicochemical properties,
      intracellular location, and cytotoxicity of conjugate micelles demonstrate that
      this novel smart drug delivery system can enhance intracellular delivery of drug
      at a low pH and then release drug rapidly.

PMID- 24733785
TI  - Lanthanide tris(beta-diketonates) as useful probes for chirality determination of
      biological amino alcohols in vibrational circular dichroism: ligand to ligand
      chirality transfer in lanthanide coordination sphere.
AB  - A series of lanthanide tris(beta-diketonates) functioned as useful chirality
      probes in the vibrational circular dichroism (VCD) characterization of biological
      amino alcohols. Various chiral amino alcohols induced intense VCD signals upon
      ternary complexation with racemic lanthanide tris(beta-diketonates). The VCD
      signals observed around 1500 cm(-1) (beta-diketonate IR absorption region)
      correlated well with the stereochemistry and enantiomeric purity of the targeted
      amino alcohol, while the corresponding monoalcohol, monoamine, and diol
      substrates induced very weak VCD signals. The high-coordination number and
      dynamic property of the lanthanide complex offer an effective chirality VCD
      probing of biological substrates.

PMID- 24733786
TI  - Optimization of the activation and nucleation steps in the precipitation of a
      calcium phosphate primer layer on electrospun poly(E-caprolactone).
AB  - The present study aimed to optimize the procedure for coating electrospun
      poly(epsilon-caprolactone) (PCL) fibers with a calcium phosphate (CP) layer in
      order to improve their potential as bone tissue engineering scaffold. In
      particular, attention was paid to the reproducibility of the procedure, the
      morphology of the coating, and the preservation of the porous structure of the
      scaffold. Ethanol dipping followed by an ultrasonic assisted hydrolysis of the
      fiber surface with sodium hydroxide solution efficiently activated the surface.
      The resulting reactive groups served as nucleation points for CP precipitation,
      induced by alternate dipping of the samples in calcium and phosphate rich
      solutions. By controlling the deposition, a reproducible thin layer of CP was
      grown onto the fiber surface. The deposited CP was identified as calcium
      deficient apatite (CDHAp). Analysis of the cell viability, adhesion, and
      proliferation of MC3T3-E1 cells on untreated and CDHAp coated PCL scaffolds
      showed that the CDHAp coating enhanced the cell response, as the number of
      attached cells was higher in comparison to the untreated PCL and cells on the
      CDHAp coated samples showed similar morphologies as the ones found in the
      positive control.

PMID- 24733787
TI  - A recombinant humanized anti-cocaine monoclonal antibody inhibits the
      distribution of cocaine to the brain in rats.
AB  - The monoclonal antibody (mAb), h2E2, is a humanized version of the chimeric
      human/murine anti-cocaine mAb 2E2. The recombinant h2E2 protein was produced in
      vitro from a transfected mammalian cell line and retained high affinity (4 nM Kd)
      and specificity for cocaine over its inactive metabolites benzoylecgonine (BE)
      and ecgonine methyl ester. In rats, pharmacokinetic studies of h2E2 (120 mg/kg
      i.v.) showed a long terminal elimination half-life of 9.0 days and a low volume
      of distribution at steady state (Vdss) of 0.3 l/kg. Pretreatment with h2E2
      produced a dramatic 8.8-fold increase in the area under the plasma cocaine
      concentration-time curve (AUC) and in brain a concomitant decrease of 68% of
      cocaine's AUC following an i.v. injection of an equimolar cocaine dose.
      Sequestration of cocaine in plasma by h2E2, shown via reduction of cocaine's
      Vdss, indicates potential clinical efficacy. Although the binding of cocaine to
      h2E2 in plasma should inhibit distribution and metabolism, the elimination of
      cocaine remained multicompartmental and was still rapidly eliminated from plasma
      despite the presence of h2E2. BE was the major cocaine metabolite, and brain BE
      concentrations were sixfold higher than in plasma, indicating that cocaine is
      normally metabolized in the brain. In the presence of h2E2, brain BE
      concentrations were decreased and plasma BE was increased, consistent with the
      observed h2E2-induced changes in cocaine disposition. The inhibition of cocaine
      distribution to the brain confirms the humanized mAb, h2E2, as a lead candidate
      for development as an immunotherapy for cocaine abuse. 

PMID- 24733788
TI  - Hepatic microsomal thiol methyltransferase is involved in stereoselective
      methylation of pharmacologically active metabolite of prasugrel.
AB  - Prasugrel, a thienopyridine antiplatelet drug, is converted in animals and humans
      to the pharmacologically active metabolite R-138727 [(2Z)-{1-[(1RS)-2-cyclopropyl
      1-(2-fluorophenyl)-2-oxoethyl]-4-sulfanylpiperidin-3-ylidene}ethanoic acid],
      which has two chiral centers, occurring as a mixture of four isomers. The RS and
      RR isomers are more active than the SS and SR isomers (RS > RR > > SR = SS). The
      pharmacologically active metabolite is further metabolized to an S-methylated
      metabolite that is the major identified inactive metabolite in humans. In rat,
      dog, and human liver microsomes supplemented with S-adenosyl methione, the SS and
      SR isomers of the active metabolite were extensively S-methylated while the RS
      and RR isomers were not. Addition of 2,3-dichloromethyl benzylamine (50 uM)
      completely inhibited the S-methylation reaction, indicating that the microsomal
      and cytosolic thiol methyltransferase but not the cytosolic thiopurine S
      methyltransferase is involved in the methylation. The hepatic intrinsic clearance
      values for methylation of the RS, RR, SS, and SR isomers (ml/min/kg) were 0, 0,
      40.4, and 37.6, respectively, in rat liver microsomes, 0, 0, 11.6, and 2.5,
      respectively, in dog liver microsomes, and 0, 0, 17.3, and 17.7, respectively, in
      human liver microsomes, indicating that the RS and RR isomers are not methylated
      in vitro and that the methylation of SS and SR isomers is high with rat > human >
      dog. This finding in vitro agreed well with the in vivo observation in rats and
      dogs, where the S-methylated SS and SR isomers were the major metabolites in the
      plasma whereas negligible amounts of S-methylated RS and RR isomers were detected
      after intravenous administration of the pharmacologically active metabolites. 

PMID- 24733789
TI  - Metabolic activation of the antibacterial agent triclocarban by cytochrome P450
      1A1 yielding glutathione adducts.
AB  - Triclocarban (3,4,4'-trichlorocarbanilide; TCC) is an antibacterial agent used in
      personal care products such as bar soaps. Small amounts of chemical are absorbed
      through the epidermis. Recent studies show that residues of reactive TCC
      metabolites are bound covalently to proteins in incubations with keratinocytes,
      raising concerns about the potential toxicity of this antimicrobial agent. To
      obtain additional information on metabolic activation of TCC, this study
      characterized the reactive metabolites trapped as glutathione conjugates.
      Incubations were carried out with (14)C-labeled TCC, recombinant CYP1A1 or
      CYP1B1, coexpressed with cytochrome P450 reductase, glutathione-S-transferases
      (GSH), and an NADPH-generating system. Incubations containing CYP1A1, but not
      1B1, led to formation of a single TCC-GSH adduct with a conversion rate of 1% of
      parent compound in 2 hours. Using high-resolution mass spectrometry and
      diagnostic fragmentation, the adduct was tentatively identified as 3,4-dichloro
      3'-glutathionyl-4'-hydroxycarbanilide. These findings support the hypothesis that
      TCC is activated by oxidative dehalogenation and oxidation to a quinone imine.
      Incubations of TCDD-induced keratinocytes with (14)C-TCC yielded a minor
      radioactive peak coeluting with TCC-GSH. Thus, we conclude that covalent protein
      modification by TCC in TCDD-induced human keratinocyte incubations is mainly
      caused by activation of TCC by CYP1A1 via a dehalogenated TCC derivative as
      reactive species. 

PMID- 24733790
TI  - NUT Midline Carcinoma Masquerading As a Thymic Carcinoma.

PMID- 24733791
TI  - Positron Emission Tomography-Computed Tomography Imaging of a Patient With
      Several Myeloid Sarcomas With FLT3-ITD and NPM1 Mutations.

PMID- 24733792
TI  - Clinical evaluation of a multiple-gene sequencing panel for hereditary cancer
      risk assessment.
AB  - PURPOSE: Multiple-gene sequencing is entering practice, but its clinical value is
      unknown. We evaluated the performance of a customized germline-DNA sequencing
      panel for cancer-risk assessment in a representative clinical sample. METHODS:
      Patients referred for clinical BRCA1/2 testing from 2002 to 2012 were invited to
      donate a research blood sample. Samples were frozen at -80 degrees  C, and DNA
      was extracted from them after 1 to 10 years. The entire coding region, exon
      intron boundaries, and all known pathogenic variants in other regions were
      sequenced for 42 genes that had cancer risk associations. Potentially actionable
      results were disclosed to participants. RESULTS: In total, 198 women participated
      in the study: 174 had breast cancer and 57 carried germline BRCA1/2 mutations.
      BRCA1/2 analysis was fully concordant with prior testing. Sixteen pathogenic
      variants were identified in ATM, BLM, CDH1, CDKN2A, MUTYH, MLH1, NBN, PRSS1, and
      SLX4 among 141 women without BRCA1/2 mutations. Fourteen participants carried 15
      pathogenic variants, warranting a possible change in care; they were invited for
      targeted screening recommendations, enabling early detection and removal of a
      tubular adenoma by colonoscopy. Participants carried an average of 2.1 variants
      of uncertain significance among 42 genes. CONCLUSION: Among women testing
      negative for BRCA1/2 mutations, multiple-gene sequencing identified 16
      potentially pathogenic mutations in other genes (11.4%; 95% CI, 7.0% to 17.7%),
      of which 15 (10.6%; 95% CI, 6.5% to 16.9%) prompted consideration of a change in
      care, enabling early detection of a precancerous colon polyp. Additional studies
      are required to quantify the penetrance of identified mutations and determine
      clinical utility. However, these results suggest that multiple-gene sequencing
      may benefit appropriately selected patients.

PMID- 24733795
TI  - Acquisition of compassion among physicians: why is this rite different from all
      other rites?

PMID- 24733793
TI  - Screening, assessment, and care of anxiety and depressive symptoms in adults with
      cancer: an American Society of Clinical Oncology guideline adaptation.
AB  - PURPOSE: A Pan-Canadian Practice Guideline on Screening, Assessment, and Care of
      Psychosocial Distress (Depression, Anxiety) in Adults With Cancer was identified
      for adaptation. METHODS: American Society of Clinical Oncology (ASCO) has a
      policy and set of procedures for adapting clinical practice guidelines developed
      by other organizations. The guideline was reviewed for developmental rigor and
      content applicability. RESULTS: On the basis of content review of the pan
      Canadian guideline, the ASCO panel agreed that, in general, the recommendations
      were clear, thorough, based on the most relevant scientific evidence, and
      presented options that will be acceptable to patients. However, for some topics
      addressed in the pan-Canadian guideline, the ASCO panel formulated a set of
      adapted recommendations based on local context and practice beliefs of the ad hoc
      panel members. It is recommended that all patients with cancer be evaluated for
      symptoms of depression and anxiety at periodic times across the trajectory of
      care. Assessment should be performed using validated, published measures and
      procedures. Depending on levels of symptoms and supplementary information,
      differing treatment pathways are recommended. Failure to identify and treat
      anxiety and depression increases the risk for poor quality of life and potential
      disease-related morbidity and mortality. This guideline adaptation is part of a
      larger survivorship guideline series. CONCLUSION: Although clinicians may not be
      able to prevent some of the chronic or late medical effects of cancer, they have
      a vital role in mitigating the negative emotional and behavioral sequelae.
      Recognizing and treating effectively those who manifest symptoms of anxiety or
      depression will reduce the human cost of cancer.

PMID- 24733794
TI  - Milestones in the curability of pediatric cancers.

PMID- 24733796
TI  - Phase IIa trial of trastuzumab emtansine with pertuzumab for patients with human
      epidermal growth factor receptor 2-positive, locally advanced, or metastatic
      breast cancer.
AB  - PURPOSE: Our phase IIa study characterized the safety and efficacy of two human
      epidermal growth factor receptor 2 (HER2) -targeted agents, trastuzumab emtansine
      (T-DM1) and pertuzumab, in patients with HER2-positive metastatic breast cancer
      (MBC). PATIENTS AND METHODS: Patients with HER2-positive locally advanced breast
      cancer or MBC were treated with 3.6 mg/kg T-DM1 plus pertuzumab (840-mg loading
      dose, then 420 mg subsequently) once every 3 weeks. The primary efficacy end
      point was investigator-assessed objective response rate (ORR). RESULTS: Sixty
      four patients (43 patients in the second-line or greater setting [advanced MBC];
      21 patients in the first-line setting [first-line MBC]) were enrolled. Patients
      with advanced MBC had received trastuzumab and a median of six prior nonhormonal
      treatments for MBC; 86% of first-line MBC patients had received trastuzumab in
      the (neo)adjuvant setting. The ORR was 41% overall, 33% in patients with advanced
      MBC, and 57% in first-line patients. Median progression-free survival was 6.6,
      5.5, and 7.7 months, respectively. The most common adverse events were fatigue
      (61%), nausea (50%), and diarrhea (39%). The most frequent grade >= 3 adverse
      events were thrombocytopenia (13%), fatigue (11%), and liver enzyme elevations
      (increased ALT: 9%; increased AST: 9%). One patient had left ventricular ejection
      fraction of less than 40% after study drug discontinuation. Exploratory biomarker
      analyses demonstrated that patients with above-median tumor HER2 mRNA levels had
      a numerically higher ORR than patients with below-median levels (44% v 33%,
      respectively). CONCLUSION: T-DM1 and pertuzumab can be combined at full doses
      with no unexpected toxicities. The preliminary efficacy in patients in the first
      line and advanced MBC settings warrants further investigation.

PMID- 24733797
TI  - Comparative effectiveness of robot-assisted and open radical prostatectomy in the
      postdissemination era.
AB  - PURPOSE: Given the lack of randomized trials comparing robot-assisted radical
      prostatectomy (RARP) and open radical prostatectomy (ORP), we sought to re
      examine the outcomes of these techniques using a cohort of patients treated in
      the postdissemination era. PATIENTS AND METHODS: Overall, data from 5,915
      patients with prostate cancer treated with RARP or ORP within the SEER-Medicare
      linked database diagnosed between October 2008 and December 2009 were abstracted.
      Postoperative complications, blood transfusions, prolonged length of stay (pLOS),
      readmission, additional cancer therapies, and costs of care within the first year
      after surgery were compared between the two surgical approaches. To decrease the
      effect of unmeasured confounders, instrumental variable analysis was performed.
      Multivariable logistic regression analyses were then performed. RESULTS: Overall,
      2,439 patients (41.2%) and 3,476 patients (58.8%) underwent ORP and RARP,
      respectively. In multivariable analyses, patients undergoing RARP had similar
      odds of overall complications, readmission, and additional cancer therapies
      compared with patients undergoing ORP. However, RARP was associated with a higher
      probability of experiencing 30- and 90-day genitourinary and miscellaneous
      medical complications (all P <= .02). Additionally, RARP led to a lower risk of
      experiencing blood transfusion and of having a pLOS (all P < .001). Finally,
      first-year reimbursements were greater for patients undergoing RARP compared with
      ORP (P < .001). CONCLUSION: RARP and ORP have comparable rates of complications
      and additional cancer therapies, even in the postdissemination era. Although RARP
      was associated with lower risk of blood transfusions and a slightly shorter
      length of stay, these benefits do not translate to a decrease in expenditures.

PMID- 24733798
TI  - Choroidal Metastases From EML4-ALK-Positive Non-Small-Cell Lung Adenocarcinoma.

PMID- 24733800
TI  - Reply to C.C. Earle.

PMID- 24733799
TI  - Doxepin rinse versus placebo in the treatment of acute oral mucositis pain in
      patients receiving head and neck radiotherapy with or without chemotherapy: a
      phase III, randomized, double-blind trial (NCCTG-N09C6 [Alliance]).
AB  - PURPOSE: Painful oral mucositis (OM) is a significant toxicity during
      radiotherapy for head and neck cancers. The aim of this randomized, double-blind,
      placebo-controlled trial was to test the efficacy of doxepin hydrochloride in the
      reduction of radiotherapy-induced OM pain. PATIENTS AND METHODS: In all, 155
      patients were randomly allocated to a doxepin oral rinse or a placebo for the
      treatment of radiotherapy-related OM pain. Patients received a single dose of
      doxepin or placebo on day 1 and then crossed over to receive the opposite agent
      on a subsequent day. Pain questionnaires were administered at baseline and at 5,
      15, 30, 60, 120, and 240 minutes. Patients were then given the option to continue
      doxepin. The primary end point was pain reduction as measured by the area under
      the curve (AUC) of the pain scale using data from day 1. RESULTS: Primary end
      point analysis revealed that the AUC for mouth and throat pain reduction was
      greater for doxepin (-9.1) than for placebo (-4.7; P < .001). Crossover analysis
      of patients completing both phases confirmed that patients experienced greater
      mouth and throat pain reduction with doxepin (intrapatient changes of 4.1 for
      doxepin-placebo arm and -2.8 for placebo-doxepin arm; P < .001). Doxepin was
      associated with more stinging or burning, unpleasant taste, and greater
      drowsiness than the placebo rinse. More patients receiving doxepin expressed a
      desire to continue treatment than did patients with placebo after completion of
      each of the randomized phases of the study. CONCLUSION: A doxepin rinse
      diminishes OM pain. Further studies are warranted to determine its role in the
      management of OM.

PMID- 24733801
TI  - Complete Cytologic Remission of V600E BRAF-Mutant Melanoma-Associated
      Leptomeningeal Carcinomatosis Upon Treatment With Dabrafenib.

PMID- 24733802
TI  - Limitations of assessing value in robotic surgery for prostate cancer: what data
      should patients and physicians use to make the best decision?

PMID- 24733804
TI  - Is more intensive surveillance really a good idea for high-risk patients with
      colorectal cancer?

PMID- 24733803
TI  - Screening, assessment, and management of fatigue in adult survivors of cancer: an
      American Society of Clinical oncology clinical practice guideline adaptation.
AB  - PURPOSE: This guideline presents screening, assessment, and treatment approaches
      for the management of adult cancer survivors who are experiencing symptoms of
      fatigue after completion of primary treatment. METHODS: A systematic search of
      clinical practice guideline databases, guideline developer Web sites, and
      published health literature identified the pan-Canadian guideline on screening,
      assessment, and care of cancer-related fatigue in adults with cancer, the
      National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines In
      Oncology (NCCN Guidelines) for Cancer-Related Fatigue and the NCCN Guidelines for
      Survivorship. These three guidelines were appraised and selected for adaptation.
      RESULTS: It is recommended that all patients with cancer be evaluated for the
      presence of fatigue after completion of primary treatment and be offered specific
      information and strategies for fatigue management. For those who report moderate
      to severe fatigue, comprehensive assessment should be conducted, and medical and
      treatable contributing factors should be addressed. In terms of treatment
      strategies, evidence indicates that physical activity interventions, psychosocial
      interventions, and mind-body interventions may reduce cancer-related fatigue in
      post-treatment patients. There is limited evidence for use of psychostimulants in
      the management of fatigue in patients who are disease free after active
      treatment. CONCLUSION: Fatigue is prevalent in cancer survivors and often causes
      significant disruption in functioning and quality of life. Regular screening,
      assessment, and education and appropriate treatment of fatigue are important in
      managing this distressing symptom. Given the multiple factors contributing to
      post-treatment fatigue, interventions should be tailored to each patient's
      specific needs. In particular, a number of nonpharmacologic treatment approaches
      have demonstrated efficacy in cancer survivors.

PMID- 24733805
TI  - Primary Cutaneous Mantle-Cell Lymphoma: A Case Report and Literature Review.

PMID- 24733806
TI  - Interpreting plasma estrogen levels in breast cancer: caution needed.

PMID- 24733807
TI  - Results of a multicenter, controlled, randomized clinical trial evaluating the
      combination of piperacillin/tazobactam and tigecycline in high-risk hematologic
      patients with cancer with febrile neutropenia.
AB  - PURPOSE: Empiric antibiotic monotherapy is considered the standard of treatment
      for febrile neutropenic patients with cancer, but this approach may be inadequate
      because of the increasing prevalence of infections caused by multidrug resistant
      (MDR) bacteria. PATIENTS AND METHODS: In this multicenter, open-label,
      randomized, superiority trial, adult, febrile, high-risk neutropenic patients
      (FhrNPs) with hematologic malignancies were randomly assigned to receive
      piperacillin/tazobactam (4.5 g intravenously every 8 hours) with or without
      tigecycline (50 mg intravenously every 12 hours; loading dose 100 mg). The
      primary end point was resolution of febrile episode without modifications of the
      initial allocated treatment. RESULTS: Three hundred ninety FhrNPs were enrolled
      (combination/monotherapy, 187/203) and were included in the intention-to-treat
      analysis (ITTA). The ITTA revealed a successful outcome in 67.9% v 44.3% of
      patients who had received combination therapy and monotherapy, respectively
      (127/187 v 90/203; absolute difference in risk (adr), 23.6%; 95% CI, 14% to 33%;
      P < .001). The combination regimen proved better than monotherapy in bacteremias
      (adr, 32.8%; 95% CI, 19% to 46%; P < .001) and in clinically documented
      infections (adr, 36%; 95% CI, 9% to 64%; P < .01). Mortality and number of
      adverse effects were limited and similar in the two groups. CONCLUSION: The
      combination of piperacillin/tazobactam and tigecycline is safe, well tolerated,
      and more effective than piperacillin/tazobactam alone in febrile, high-risk,
      neutropenic hematologic patients with cancer. In epidemiologic settings
      characterized by a high prevalence of infections because of MDR microorganisms,
      this combination could be considered as one of the first-line empiric antibiotic
      therapies.

PMID- 24733809
TI  - Optofluidic rotation of living cells for single-cell tomography.
AB  - Flow cytometry provides a high throughput, multi-dimensional analysis of cells
      flowing in suspension. In order to combine this feature with the ability to
      resolve detailed structures in 3D, we developed an optofluidic device that
      combines a microfluidic system with a dual beam trap. This allows for the
      rotation of single cells in a continuous flow, around an axis perpendicular to
      the imaging plane. The combination of both techniques enables the tomographic
      reconstruction of the 3D structure of the cell. In addition this method is
      capable to provide detailed 3D structural data for flow cytometry, as it improves
      the reconstructed z-resolution of a standard microscopy system to produce images
      with isotropic resolution in all three axes. 

PMID- 24733808
TI  - Prevention and management of chemotherapy-induced peripheral neuropathy in
      survivors of adult cancers: American Society of Clinical Oncology clinical
      practice guideline.
AB  - PURPOSE: To provide evidence-based guidance on the optimum prevention and
      treatment approaches in the management of chemotherapy-induced peripheral
      neuropathies (CIPN) in adult cancer survivors. METHODS: A systematic literature
      search identified relevant, randomized controlled trials (RCTs) for the treatment
      of CIPN. Primary outcomes included incidence and severity of neuropathy as
      measured by neurophysiologic changes, patient-reported outcomes, and quality of
      life. RESULTS: A total of 48 RCTs met eligibility criteria and comprise the
      evidentiary basis for the recommendations. Trials tended to be small and
      heterogeneous, many with insufficient sample sizes to detect clinically important
      differences in outcomes. Primary outcomes varied across the trials, and in most
      cases, studies were not directly comparable because of different outcomes,
      measurements, and instruments used at different time points. The strength of the
      recommendations is based on the quality, amount, and consistency of the evidence
      and the balance between benefits and harms. RECOMMENDATIONS: On the basis of the
      paucity of high-quality, consistent evidence, there are no agents recommended for
      the prevention of CIPN. With regard to the treatment of existing CIPN, the best
      available data support a moderate recommendation for treatment with duloxetine.
      Although the CIPN trials are inconclusive regarding tricyclic antidepressants
      (such as nortriptyline), gabapentin, and a compounded topical gel containing
      baclofen, amitriptyline HCL, and ketamine, these agents may be offered on the
      basis of data supporting their utility in other neuropathic pain conditions given
      the limited other CIPN treatment options. Further research on these agents is
      warranted.

PMID- 24733810
TI  - The Association Between Admission Magnesium Concentrations and Lactic Acidosis in
      Critical Illness.
AB  - INTRODUCTION: Although magnesium plays an important role in aerobic metabolism
      and magnesium deficiency is a common phenomenon in critical illness, the
      association between magnesium deficiency and lactic acidosis in the intensive
      care unit (ICU) has not been defined. METHODS: This was a retrospective, cross
      sectional study conducted at a 77 ICU bed tertiary medical center. Data
      pertaining to the first unique admission of any ICU patient between 2001 and 2008
      were extracted from the Multiparameter Intelligent Monitoring in Intensive Care
      database. Hypomagnesemia was defined as serum magnesium <1.6 mg/dL. Mild and
      severe lactic acidosis were defined as lactate concentrations of >2 and > 4
      mmol/L, respectively. Multivariate modeling was used to explore the association
      between magnesium and lactate concentrations. RESULTS: Of 8922 critically ill
      patients, 22.6% were hypomagnesemic. Hypomagnesemia was associated with an
      increased adjusted risk of mild lactic acidosis (odds ratio [OR] 1.71, 95%
      confidence interval [95%CI] 1.51-1.94, P < .001) and severe lactic acidosis (OR
      1.56, 95%CI 1.32-1.84, P < .001) than the reference quartile. The association
      between hypomagnesemia and mild lactic acidosis was stronger in those at risk of
      magnesium deficiency, including diabetics (OR 2.02, 95%CI 1.51-2.72, P < .001)
      and alcoholics (OR 1.92, 95%CI 1.16-3.19, P = .01). As an internal model control,
      hypokalemia was not associated with an increased risk of lactic acidosis.
      CONCLUSIONS: Magnesium deficiency is a common finding in patients admitted to the
      ICU and is associated with lactic acidosis. Our findings support the biologic
      role of magnesium in metabolism and raise the possibility that hypomagnesemia is
      a correctable risk factor for lactic acidosis in critical illness.

PMID- 24733811
TI  - Growth factor conjugation: strategies and applications.
AB  - Growth factors, first known for their essential role in the initiation of
      mitosis, are required for a variety of cellular processes and their localized
      delivery is considered as a rational approach in their therapeutic application to
      assure a safe and effective treatment while avoiding unwanted adverse effects.
      Noncovalent immobilization of growth factors as well as their covalent
      conjugation is amongst the most common strategies for localized delivery of
      growth factors. Today, immobilized and covalently conjugated growth factors are
      considered as a promising drug design and are widely used for protein
      reformulation and material design to cover the unwanted characteristics of growth
      factors as well as improving their functions. Selection of a suitable conjugation
      technique depends on the substrate chemistry and the availability of functional
      reactive groups in the structure of growth factor, the position of reactive
      groups in growth factor molecules and its relation with the receptor binding
      area, and the intention of creating either patterned or unpatterned conjugation.
      Various approaches for growth factor reformulation have been reported. This
      review provides an overview on chemical conjugation of growth factors and covers
      the relevant studies accomplished for bioconjugation of growth factors and their
      related application.

PMID- 24733812
TI  - Dual-polarization Raman spectral imaging to extract overlapping molecular
      fingerprints of living cells.
AB  - Raman spectral imaging is gaining more and more attention in biological studies
      because of its label-free characteristic. However, the discrimination of
      overlapping chemical contrasts has been a major challenge. In this study, we
      introduce an optical method to simultaneously obtain two orthogonally polarized
      Raman images from a single scan of the sample. We demonstrate how this technique
      can improve the quality and quantity of the hyperspectral Raman dataset and how
      the technique is expected to further extend the horizons of Raman spectral
      imaging in biological studies by providing more detailed chemical information.
      The dual-polarization Raman images of a HeLa cell. 

PMID- 24733813
TI  - Climate extremes drive changes in functional community structure.
AB  - The response of communities to climate extremes can be quite variable. Much of
      this variation has been attributed to differences in community-specific
      functional trait diversity, as well as community composition. Yet, few if any
      studies have explicitly tested the response of the functional trait structure of
      communities following climate extremes (CEs). Recently in South Florida, two
      independent, but sequential potential CEs took place, a 2010 cold front, followed
      by a 2011 drought, both of which had profound impacts on a subtropical estuarine
      fish community. These CEs provided an opportunity to test whether the structure
      of South Florida fish communities following each extreme was a result of species
      specific differences in functional traits. From historical temperature (1927
      2012) and freshwater inflows records into the estuary (1955-2012), we determined
      that the cold front was a statistically extreme disturbance, while the drought
      was not, but rather a decadal rare disturbance. The two disturbances predictably
      affected different parts of functional community structure and thus different
      component species. The cold front virtually eliminated tropical species,
      including large-bodied snook, mojarra species, nonnative cichlids, and striped
      mullet, while having little affect on temperate fishes. Likewise, the drought
      severely impacted freshwater fishes including Florida gar, bowfin, and two
      centrarchids, with little effect on euryhaline species. Our findings illustrate
      the ability of this approach to predict and detect both the filtering effects of
      different types of disturbances and the implications of the resulting changes in
      community structure. Further, we highlight the value of this approach to
      developing predictive frameworks for better understanding community responses to
      global change. 

PMID- 24733814
TI  - In vitro age dependent response of macrophages to micro and nano titanium dioxide
      particles.
AB  - As a result of corrosion, microparticles (MP) and/or nanoparticles (NP) can be
      released from the metallic implants surface into the bioenvironment. The
      biological response to these particles depends not only on the physico-chemical
      properties of the particles but also on host factors, such as age. Macrophages
      have attracted wide concern in biomedicine. The aim of this investigation was to
      study the age related biological response of macrophages to TiO2 -MP and NP in
      vitro. Alveolar macrophages (AM) obtained from young and senescent rats were
      cultured and exposed to TiO2 -MP and NP. Cell metabolism, superoxide anion (O2 (
      ) ) and nitric oxide (NO) generation, and cytokine release (IL-6, TNFalpha, IL
      10) were measured. Cell metabolism was not affected by particle exposure. O2 (-)
      and NO generation increased in a dose dependent manner. A marked increase on IL-6
      release was found in the young-AM subpopulation exposed to TiO2 -MP. Conversely,
      both particle sizes induced a dose dependent release of TNFalpha in senescent-AM.
      Only the highest concentration of TiO2 -particles caused a significant increase
      in IL-10 release in AM-cultures. These observations lend strong support to the
      suggestion that cellular response of macrophages to TiO2 -particles is age
      dependent. The biological effect of the particles would seem to be more
      deleterious in the senescent age-group.

PMID- 24733815
TI  - Clinical use of the Kessler psychological distress scales with culturally diverse
      groups.
AB  - The Kessler 10 (K10) and embedded Kessler 6 (K6) was developed to screen for non
      specific psychological distress and serious mental illness in mental health
      surveys of English-speaking populations, but has been adopted in Western and non
      Western countries as a screening and outcome measure in primary care and mental
      health settings. This review examines whether the original K6/K10's validity for
      culturally diverse populations was established, and whether the cultural
      equivalence, and sensitivity to change of translated or culturally adapted
      K6/K10s, has been demonstrated with culturally diverse client groups. Evidence
      for the original K6/K10's validity for culturally diverse populations is limited.
      Questions about the conceptual and linguistic equivalence of translated/adapted
      K6/K10s arise from reports of changes in item connotation and differential item
      functioning. Evidence for structural equivalence is inconsistent, as is support
      for criterion equivalence, with the majority of studies compromising on accuracy
      in case prediction. Research demonstrating sensitivity to change with culturally
      diverse groups is lacking. Inconsistent evidence for the K6/K10's cultural
      appropriateness in clinical settings, and a lack of clinical norms for either
      majority or culturally diverse groups, indicate the importance of further
      research into the psychological distress construct with culturally diverse
      clients, and the need for caution in interpreting K6/K10 scores.

PMID- 24733816
TI  - Isotropic high resolution optoacoustic imaging with linear detector arrays in bi
      directional scanning.
AB  - Optoacoustic (photoacoustic) imaging is often performed with one-dimensional
      transducer arrays, in analogy to ultrasound imaging. Optoacoustic imaging using
      linear arrays offers ease of implementation but comes with several performance
      drawbacks, in particular poor elevation resolution, i.e. the resolution along the
      axis perpendicular to the focal plane. Herein, we introduce and investigate a bi
      directional scanning approach using linear arrays that can improve the imaging
      performance to quasi-isotropic transverse resolution. We study the approach
      theoretically and perform numerical simulations and phantom measurements to
      evaluate its performance under defined conditions. Finally, we discuss the
      features and the limitations of the proposed method.

PMID- 24733817
TI  - Using the International Classification of Functioning, Disability and Health in
      Physiotherapy in Multidisciplinary Vocational Rehabilitation: A Case Study of Low
      Back Pain.
AB  - OBJECTIVES: Multidisciplinary teamwork is increasingly recognized as a critical
      factor of success in vocational rehabilitation. Although its clinical
      implementation is still challenging, the International Classification of
      Functioning, Disability and Health (ICF) has shown to be a useful framework to
      facilitate communication between stakeholders, to help structure rehabilitation
      plans and for setting goals and clarifying team roles. With this in mind, the
      objective of this teaching case study is to illustrate an application of ICF
      based tools in a multidisciplinary return to work (RTW) program for patients with
      non-specific low back pain (NLBP) from the perspective of the physiotherapist.
      PARTICIPANT: The participant is a 42-year-old kindergarten teacher, who was on
      sick leave for 10 weeks due to NLBP. METHODS: This case study describes the use
      of ICF-based tools such as the Rehabilitation Management Sheet (RehabManagement
      Sheet) to guide the rehabilitation process and facilitate team-based and
      physiotherapist goal setting and documentation in a multidisciplinary RTW program
      for NLBP. RESULTS: Utilizing ICF tools, we defined long-term and short-term
      goals, documented improvements in the patient's impairments, activity
      limitations, and participation restrictions and formulated action steps.
      CONCLUSION: The use of ICF-based tools in multidisciplinary rehabilitation allows
      for a comprehensive assessment, common goal setting and coordinated intervention
      planning. ICF-based tools like the RehabManagement-Sheet support the
      physiotherapist's role within the rehabilitation team by enhancing transparency
      in goal setting and intervention planning across disciplines.

PMID- 24733818
TI  - Anxiety and Depression in Children With Nonverbal Learning Disabilities, Reading
      Disabilities, or Typical Development.
AB  - The main goal of the present study was to shed further light on the psychological
      characteristics of children with different learning disability profiles aged
      between 8 and 11 years, attending from third to sixth grade. Specifically,
      children with nonverbal learning disabilities (NLD), reading disabilities (RD),
      or a typical development (TD) were tested. In all, 15 children with NLD, 15 with
      RD, and 15 with TD were administered self-report questionnaires to assess
      different types of anxiety and depression symptoms. Both NLD and RD children
      reported experiencing more generalized and social anxiety than TD, the NLD
      children reported more severe anxiety about school and separation than TD, and
      the children with RD had worse depressive symptoms than those with NLD or TD. 

PMID- 24733819
TI  - A Study of the Relationships Among Chinese Multicharacter Words, Subtypes of
      Readers, and Instructional Methods.
AB  - This article reports the results of two studies examining the effectiveness of
      the whole-word and analytic instructional methods in teaching different subtypes
      of readers (students with normal reading performance, surface dyslexics,
      phonological dyslexics, and both dyslexic patterns) and four kinds of Chinese two
      character words (two regular [RR], two irregular [II], one regular, one irregular
      [RI], and one irregular, one regular [IR]). The approaches employed were the
      analytic method, which focuses on highlighting the phonological components of
      words, and the whole-word method, which focuses on learning by sight. Two studies
      were conducted among a sample of 40 primary school students with different
      reading patterns. The aim was to examine the relationships among different
      subtypes of readers, two-character words, and instructional methods. In general,
      students with a surface dyslexic pattern benefited more from the analytic
      methods. Regarding combinations of different kinds of two-character words, all
      subtypes of students performed better in reading RR words than in reading II
      words. 

PMID- 24733820
TI  - Patient advocates as partners in genetic research: investigators see benefits of
      forging relationships with disease advocacy groups.

PMID- 24733821
TI  - Gender plays role in predicting neuronal dysfunction for patients with
      neurofibromatosis 1: girls more likely to require treatment for visual decline
      caused by NF1-related brain tumors.

PMID- 24733823
TI  - Tips for single-port laparoscopic cholecystectomy.
AB  - Single-port laparoscopic cholecystectomy (SPLC) is an emerging technique and
      gaining increased attention by its superiority in cosmesis. A 1.5-cm vertical
      transumbilical incision is used for the single port, followed by the glove
      method. Indications for SPLC are the same as those for standard 4-port
      laparoscopic cholecystectomy, including patients with morbid obesity, previous
      upper abdominal surgery, severe acute cholecystitis, or suspected presence of
      common bile duct stones. Some randomized controlled trials have shown negative
      results of SPLC regarding operative time, wound-related complications, and
      postoperative pain. However, our retrospective analysis shows equivalent clinical
      outcomes among the two approaches in terms of postoperative pain and
      complications. In this context, SPLC can be a good option for gallbladder
      pathologies. 

PMID- 24733827
TI  - Hedgehog pathway as a potential treatment target in human cholangiocarcinoma.
AB  - BACKGROUND: Innovative treatment concepts targeting essential signaling pathways
      may offer new chances for patients suffering from cholangiocarcinoma (CCC). For
      that, we performed a systematic molecular genetic analysis concerning the
      Hedgehog activity in human CCC samples and analyzed the effect of Hh inhibition
      on CCC cells in vitro and in vivo. METHODS: Activation of the Hh pathway was
      analyzed in 50 human CCC samples using quantitative polymerase chain reaction
      (qPCR). The efficacy of Hh inhibition using cyclopamine and BMS-833923 was
      evaluated in vitro. In addition, the effect of BMS-833923, alone or in
      combination with gemcitabine, was analyzed in vivo in a murine subcutaneous
      xenograft model. RESULTS: Expression analysis revealed a significant activation
      of the Hh-signaling pathway in nearly 50% of CCCs. Hh inhibition resulted in a
      significant decrease in cell proliferation of CCC cells. Moreover, a distinct
      inhibition of tumor growth could be seen as a result of a combined therapy with
      BMS-833923 and gemcitabine in CCC xenografts. CONCLUSION: The results of our
      study suggest that the Hh pathway plays a relevant role at least in a subset of
      human CCC. Inhibition of this pathway may represent a possible treatment option
      for CCC patients in which the Hh pathway is activated.

PMID- 24733828
TI  - Targeting CXCR7/ACKR3 as a therapeutic strategy to promote remyelination in the
      adult central nervous system.
AB  - Current treatment modalities for the neurodegenerative disease multiple sclerosis
      (MS) use disease-modifying immunosuppressive compounds but do not promote repair.
      Although several potential targets that may induce myelin production have been
      identified, there has yet to be an approved therapy that promotes remyelination
      in the damaged central nervous system (CNS). Remyelination of damaged axons
      requires the generation of new oligodendrocytes from oligodendrocyte progenitor
      cells (OPCs). Although OPCs are detected in MS lesions, repair of myelin is
      limited, contributing to progressive clinical deterioration. In the CNS, the
      chemokine CXCL12 promotes remyelination via CXCR4 activation on OPCs, resulting
      in their differentiation into myelinating oligodendrocytes. Although the CXCL12
      scavenging receptor CXCR7/ACKR3 (CXCR7) is also expressed by OPCs, its role in
      myelin repair in the adult CNS is unknown. We show that during cuprizone-induced
      demyelination, in vivo CXCR7 antagonism augmented OPC proliferation, leading to
      increased numbers of mature oligodendrocytes within demyelinated lesions. CXCR7
      mediated effects on remyelination required CXCR4 activation, as assessed via both
      phospho-S339-CXCR4-specific antibodies and administration of CXCR4 antagonists.
      These findings identify a role for CXCR7 in OPC maturation during remyelination
      and are the first to use a small molecule to therapeutically enhance myelin
      repair in the demyelinated adult CNS. 

PMID- 24733829
TI  - Identification of a human splenic marginal zone B cell precursor with NOTCH2
      dependent differentiation properties.
AB  - Mouse splenic marginal zone precursors (MZPs) differentiate into marginal zone B
      (MZB) cells under a signaling pathway involving Notch2 and its ligand, delta-like
      1 ligand (Dll1). We report the identification of an MZP subset in the spleen of
      young children. These MZPs differentiate into MZ-like B cells in vitro in the
      presence of OP9 cells expressing human DLL1, as demonstrated by the up-regulation
      of classical MZB cell markers. A set of diagnostic genes discriminating
      IgM(+)IgD(+)CD27(+) blood and splenic MZB cells from switched B cells was
      identified (up-regulation of SOX7, down-regulation of TOX, COCH, and HOPX), and
      their expression during the induction assay mirrored the one of MZB cells.
      Moreover, Alagille patients with a NOTCH2 haploinsufficiency display a marked
      reduction of IgM(+)IgD(+)CD27(+) B cells in blood, whereas their switched memory
      B cells are not affected. Altogether, these results argue in favor of the
      existence of a rodent-like MZB cell lineage in humans. 

PMID- 24733830
TI  - Lymphatic function is required prenatally for lung inflation at birth.
AB  - Mammals must inflate their lungs and breathe within minutes of birth to survive.
      A key regulator of neonatal lung inflation is pulmonary surfactant, a lipoprotein
      complex which increases lung compliance by reducing alveolar surface tension
      (Morgan, 1971). Whether other developmental processes also alter lung mechanics
      in preparation for birth is unknown. We identify prenatal lymphatic function as
      an unexpected requirement for neonatal lung inflation and respiration. Mice
      lacking lymphatic vessels, due either to loss of the lymphangiogenic factor CCBE1
      or VEGFR3 function, appear cyanotic and die shortly after birth due to failure of
      lung inflation. Failure of lung inflation is not due to reduced surfactant levels
      or altered development of the lung but is associated with an elevated wet/dry
      ratio consistent with edema. Embryonic studies reveal active lymphatic function
      in the late gestation lung, and significantly reduced total lung compliance in
      late gestation embryos that lack lymphatics. These findings reveal that lymphatic
      vascular function plays a previously unrecognized mechanical role in the
      developing lung that prepares it for inflation at birth. They explain respiratory
      failure in infants with congenital pulmonary lymphangiectasia, and suggest that
      inadequate late gestation lymphatic function may also contribute to respiratory
      failure in premature infants. 

PMID- 24733832
TI  - Hypergonadotropic hypogonadism and hypersegmented neutrophils in a patient with
      ataxia-telangiectasia-like disorder: potential diagnostic clues?
AB  - Ataxia-telangiectasia-like disorder (ATLD) is a rare autosomal recessive
      disorder, and has symptoms similar to ataxia-telangiectasia (AT). ATLD is caused
      by mutations in the MRE11 gene, involved in DNA double-strand break repair
      (DSBR). In contrast to AT, ATLD patients lack key clinical features, such as
      telangiectasia or immunodeficiency, and are therefore difficult to be diagnosed.
      We report a female ATLD patient presenting with hypergonadotropic hypogonadism
      and hypersegmented neutrophils, previously undescribed features in this disorder,
      and potential diagnostic clues to differentiate ATLD from other conditions. The
      patient showed slowly progressive cerebellar ataxia from 2 years of age, and MRI
      revealed atrophy of the cerebellum, oculomotor apraxia, mild cognitive
      impairment, writing dystonia, hypergonadotropic hypogonadism with primary
      amenorrhea, and hypersegmented neutrophils. Western blot assay demonstrated total
      loss of MRE11 and reduction of ATM-dependent phosphorylation; thus, we diagnosed
      ATLD. Genetically, a novel missense mutation (c.140C>T) was detected in the MRE11
      gene, but no other mutation was found in the patient. Our presenting patient
      suggests that impaired DSBR may be associated with hypergonadotropic hypogonadism
      and neutrophil hypersegmentation. In conclusion, when assessing patients with
      ataxia of unknown cause, ATLD should be considered, and the gonadal state and
      peripheral blood smear samples evaluated.

PMID- 24733831
TI  - B-RAF kinase drives developmental axon growth and promotes axon regeneration in
      the injured mature CNS.
AB  - Activation of intrinsic growth programs that promote developmental axon growth
      may also facilitate axon regeneration in injured adult neurons. Here, we
      demonstrate that conditional activation of B-RAF kinase alone in mouse embryonic
      neurons is sufficient to drive the growth of long-range peripheral sensory axon
      projections in vivo in the absence of upstream neurotrophin signaling. We further
      show that activated B-RAF signaling enables robust regenerative growth of sensory
      axons into the spinal cord after a dorsal root crush as well as substantial axon
      regrowth in the crush-lesioned optic nerve. Finally, the combination of B-RAF
      gain-of-function and PTEN loss-of-function promotes optic nerve axon extension
      beyond what would be predicted for a simple additive effect. We conclude that
      cell-intrinsic RAF signaling is a crucial pathway promoting developmental and
      regenerative axon growth in the peripheral and central nervous systems. 

PMID- 24733833
TI  - Modulation of microRNA expression by volatile organic compounds in mouse lung.
AB  - Volatile organic compounds (VOCs) are one of main pollutants indoors. Exposure to
      VOCs is associated with cancer, asthma disease, and multiple chemical allergies.
      Despite the adverse health effects of VOCs, the molecular mechanisms underlying
      VOCs-induced disease remain largely unknown. MicroRNAs (miRNAs), as key post
      transcriptional regulators of gene expression, may influence cellular disease
      state. To investigate whether lung miRNA expression profiles in mice are modified
      by VOCs mixture exposure, 44 male Kunming mice were exposed in 4 similar static
      chambers, 0 (control) and 3 different doses of VOCs mixture (groups 1-3). The
      concentrations of VOCs mixture were as follows: formaldehyde, benzene, toluene,
      and xylene 3.0 + 3.3 + 6.0 + 6.0 mg/m(3) , 5.0 + 5.5 + 10.0 + 10.0 mg/m(3) , 10.0
      + 11.0 + 20.0 + 20.0 mg/m(3) , respectively, which corresponded to 30, 50, and
      100 times of indoor air quality standard in China, after exposure to 2 weeks (2
      h/day, 5 days/week). Small RNAs in lung and protein isolated from bronchoalveolar
      lavage fluid (BALF) were collected and analyzed for miRNA expression using
      microarray analysis and for interleukin-8 (IL-8) protein levels by enzyme-linked
      immunosorbent assay, respectively. VOCs exposure altered the miRNA expression
      profiles in lung in mice. Specifically, 69 miRNAs were significantly
      differentially expressed in VOCs-exposed samples versus controls. Functional
      annotation analysis of the predicted miRNA transcript targets revealed that VOCs
      exposure potentially alters signaling pathways associated with cancer, chemokine
      signaling, Wnt signaling, neuroactive ligand-receptor interaction, and cell
      adhesion molecules. IL-8 isolated from BALF and nitric oxide synthase of lung
      increased significantly, whereas GSH of lung decreased significantly in mice
      exposed to VOCs. These results indicate that inhalation of VOCs alters miRNA
      patterns that regulate gene expression, potentially leading to the initiation of
      cancer and inflammatory diseases.

PMID- 24733834
TI  - Protective effect of melatonin on propoxur-induced impairment of memory and
      oxidative stress in rats.
AB  - Propoxur (a carbamate pesticide) has been shown to adversely affect memory and
      induce oxidative stress on both acute and chronic exposure. This study was
      designed to explore the modulation of the effects of propoxur over cognitive
      function by melatonin (MEL). Cognitive function was assessed using step-down
      latency (SDL) on a passive avoidance apparatus, and transfer latency (TL) on an
      elevated plus maze. Oxidative stress was assessed by examining brain
      malondialdehyde (MDA) and reduced glutathione (GSH) levels and catalase (CAT)
      activity. A significant reduction in SDL and prolongation of TL was observed for
      the propoxur (10 mg/kg/d; p.o.) treated group at weeks 6 and 7 when compared with
      control. One week treatment with MEL (50 mg/kg/d; i.p.) antagonized the effect of
      propoxur on SDL, as well as TL. Propoxur produced a statistically significant
      increase in the brain MDA levels and decrease in the brain GSH levels and CAT
      activity. Treatment with MEL attenuated the effect of propoxur on oxidative
      stress. The results of the present study thus show that MEL has the potential to
      attenuate cognitive dysfunction and oxidative stress induced by toxicants like
      propoxur in the brain.

PMID- 24733835
TI  - Surgical education using a multi-viewpoint and multi-layer three-dimensional
      atlas of surgical anatomy (with video).
AB  - BACKGROUND: Trainee surgeons must have a good understanding of surgical anatomy.
      Especially in the hepatobiliary-pancreatic field, beginning surgeons often find
      it difficult to recognize the three-dimensional structure of the target organ and
      its complex anatomical correlation with surrounding organs. Conventional anatomy
      textbooks are not written with the aim of teaching these three-dimensional
      structures and complex correlations. We developed a novel teaching atlas of
      surgical anatomy using a multi-viewpoint and multi-layer three-dimensional camera
      system. METHODS: Layer-by-layer dissection of the upper abdominal organs of a
      cadaver was performed by expert surgeons. A stereoscopic camera system was used
      to capture a series of anatomical views. The images were remodeled in a multi
      viewpoint and multi-layer manner. RESULTS: Images of each dissection layer could
      be viewed serially from the appropriate angle, which was tilted up to 90 degrees 
      along the anteroposterior axis. The clinical anatomy specific to the surgical
      procedure could thus be learned using this atlas system. CONCLUSIONS: Rotatable
      three-dimensional panoramic views of local dissection of the upper abdominal
      organs of a cadaver were developed for educational purposes. Trainee surgeons
      could use these anatomical images instead of conventional anatomical atlases to
      learn how to perform surgical procedures such as pancreaticoduodenectomy and
      major hepatectomy.

PMID- 24733836
TI  - State-dependent block of Orai3 TM1 and TM3 cysteine mutants: insights into 2-APB
      activation.
AB  - After endoplasmic reticulum (ER) Ca(2+) store depletion, Orai channels in the
      plasma membrane (PM) are activated directly by ER-resident stromal interacting
      molecule (STIM) proteins to form the Ca(2+)-selective Ca(2+) release-activated
      Ca(2+) (CRAC) channel. Of the three human Orai channel homologues, only Orai3 can
      be activated by high concentrations (>50 uM) of 2-aminoethyl diphenylborinate (2
      APB). 2-APB activation of Orai3 occurs without STIM1-Orai3 interaction or store
      depletion, and results in a cationic, nonselective current characterized by
      biphasic inward and outward rectification. Here we use cysteine scanning
      mutagenesis, thiol-reactive reagents, and patch-clamp analysis to define the
      residues that assist in formation of the 2-APB-activated Orai3 pore. Mutating
      transmembrane (TM) 1 residues Q83, V77, and L70 to cysteine results in
      potentiated block by cadmium ions (Cd(2+)). TM1 mutants E81C, G73A, G73C, and
      R66C form channels that are not sensitive to 2-APB activation. We also find that
      Orai3 mutant V77C is sensitive to block by 2-aminoethyl methanethiosulfonate
      (MTSEA), but not 2-(trimethylammonium)ethyl methanethiosulfonate (MTSET). Block
      induced by reaction with MTSEA is state dependent, as it occurs only when Orai3
      V77C channels are opened by either 2-APB or by cotransfection with STIM1 and
      concurrent passive store depletion. We also analyzed TM3 residue E165. Mutation
      E165A in Orai3 results in diminished 2-APB-activated currents. However, it has
      little effect on store-operated current density. Furthermore, mutation E165C
      results in Cd(2+)-induced block that is state dependent: Cd(2+) only blocks 2-APB
      activated, not store-operated, mutant channels. Our data suggest that the dilated
      pore of 2-APB-activated Orai3 is lined by TM1 residues, but also allows for TM3
      E165 to approach the central axis of the channel that forms the conducting
      pathway, or pore.

PMID- 24733837
TI  - State-dependent and site-directed photodynamic transformation of HCN2 channel by
      singlet oxygen.
AB  - Singlet oxygen ((1)O2), which is generated through metabolic reactions and
      oxidizes numerous biological molecules, has been a useful tool in basic research
      and clinical practice. However, its role as a signaling factor, as well as a
      mechanistic understanding of the oxidation process, remains poorly understood.
      Here, we show that hyperpolarization-activated, cAMP-gated (HCN) channels--which
      conduct the hyperpolarization-activated current (Ih) and the voltage-insensitive
      instantaneous current (Iinst), and contribute to diverse physiological functions
      including learning and memory, cardiac pacemaking, and the sensation of pain--are
      subject to modification by (1)O2. To increase the site specificity of (1)O2
      generation, we used fluorescein-conjugated cAMP, which specifically binds to HCN
      channels, or a chimeric channel in which an in-frame (1)O2 generator (SOG)
      protein was fused to the HCN C terminus. Millisecond laser pulses reduced Ih
      current amplitude, slowed channel deactivation, and enhanced Iinst current. The
      modification of HCN channel function is a photodynamic process that involves
      (1)O2, as supported by the dependence on dissolved oxygen in solutions, the
      inhibitory effect by a (1)O2 scavenger, and the results with the HCN2-SOG fusion
      protein. Intriguingly, (1)O2 modification of the HCN2 channel is state dependent:
      laser pulses applied to open channels mainly slow down deactivation and increase
      Iinst, whereas for the closed channels, (1)O2 modification mainly reduced Ih
      amplitude. We identified a histidine residue (H434 in S6) near the activation
      gate in the pore critical for (1)O2 modulation of HCN function. Alanine
      replacement of H434 abolished the delay in channel deactivation and the
      generation of Iinst induced by photodynamic modification. Our study provides new
      insights into the instantaneous current conducted by HCN channels, showing that
      modifications to the region close to the intracellular gate underlie the
      expression of Iinst, and establishes a well-defined model for studying (1)O2
      modifications at the molecular level.

PMID- 24733838
TI  - Intracellular calcium movements during relaxation and recovery of superfast
      muscle fibers of the toadfish swimbladder.
AB  - The mating call of the Atlantic toadfish is generated by bursts of high-frequency
      twitches of the superfast twitch fibers that surround the swimbladder. At 16
      degrees C, a calling period can last several hours, with individual 80-100-Hz
      calls lasting ~ 500 ms interleaved with silent periods (intercall intervals)
      lasting ~ 10 s. To understand the intracellular movements of Ca(2+) during the
      intercall intervals, superfast fibers were microinjected with fluo-4, a high
      affinity fluorescent Ca(2+) indicator, and stimulated by trains of 40 action
      potentials at 83 Hz, which mimics fiber activity during calling. The fluo-4
      fluorescence signal was measured during and after the stimulus trains; the signal
      was also simulated with a kinetic model of the underlying myoplasmic Ca(2+)
      movements, including the binding and transport of Ca(2+) by the sarcoplasmic
      reticulum (SR) Ca(2+) pumps. The estimated total amount of Ca(2+) released from
      the SR during a first stimulus train is ~ 6.5 mM (concentration referred to the
      myoplasmic water volume). At 40 ms after cessation of stimulation, the myoplasmic
      free Ca(2+) concentration ([Ca(2+)]) is below the threshold for force generation
      (~ 3 uM), yet the estimated concentration of released Ca(2+) remaining in the
      myoplasm (Delta[CaM]) is large, ~ 5 mM, with ~ 80% bound to parvalbumin. At 10 s
      after stimulation, [Ca(2+)] is ~ 90 nM (three times the assumed resting level)
      and Delta[CaM] is ~ 1.3 mM, with 97% bound to parvalbumin. Ca(2+) movements
      during the intercall interval thus appear to be strongly influenced by (a) the
      accumulation of Ca(2+) on parvalbumin and (b) the slow rate of Ca(2+) pumping
      that ensues when parvalbumin lowers [Ca(2+)] near the resting level. With
      repetitive stimulus trains initiated at 10-s intervals, Ca(2+) release and
      pumping come quickly into balance as a result of the stability (negative
      feedback) supplied by the increased rate of Ca(2+) pumping at higher [Ca(2+)].

PMID- 24733840
TI  - The importance of basic science in clinical cardiology.

PMID- 24733839
TI  - The state of the art of odorant receptor deorphanization: a report from the
      orphanage.
AB  - The odorant receptors (ORs) provide our main gateway to sensing the world of
      volatile chemicals. This involves a complex encoding process in which multiple
      ORs, each of which detects its own set of odorants, work as an ensemble to
      produce a distributed activation code that is presumably unique to each odorant.
      One marked challenge to decoding the olfactory code is OR deorphanization, the
      identification of a set of activating odorants for a particular receptor. Here,
      we survey various methods used to try to express defined ORs of interest. We also
      suggest strategies for selecting odorants for test panels to evaluate the
      functional expression of an OR. Integrating these tools, while retaining
      awareness of their idiosyncratic limitations, can provide a multi-tiered approach
      to OR deorphanization, spanning the initial discovery of a ligand to vetting that
      ligand in a physiologically relevant setting. 

PMID- 24733841
TI  - Crystal structures of the structure-selective nuclease Mus81-Eme1 bound to flap
      DNA substrates.
AB  - The Mus81-Eme1 complex is a structure-selective endonuclease with a critical role
      in the resolution of recombination intermediates during DNA repair after
      interstrand cross-links, replication fork collapse, or double-strand breaks. To
      explain the molecular basis of 3' flap substrate recognition and cleavage
      mechanism by Mus81-Eme1, we determined crystal structures of human Mus81-Eme1
      bound to various flap DNA substrates. Mus81-Eme1 undergoes gross substrate
      induced conformational changes that reveal two key features: (i) a hydrophobic
      wedge of Mus81 that separates pre- and post-nick duplex DNA and (ii) a "5' end
      binding pocket" that hosts the 5' nicked end of post-nick DNA. These features are
      crucial for comprehensive protein-DNA interaction, sharp bending of the 3' flap
      DNA substrate, and incision strand placement at the active site. While Mus81-Eme1
      unexpectedly shares several common features with members of the 5' flap nuclease
      family, the combined structural, biochemical, and biophysical analyses explain
      why Mus81-Eme1 preferentially cleaves 3' flap DNA substrates with 5' nicked ends.

PMID- 24733842
TI  - Coordination of transposon expression with DNA replication in the targeting of
      telomeric retrotransposons in Drosophila.
AB  - In Drosophila, a group of retrotransposons is mobilized exclusively to telomeres
      in a sequence-independent manner. How they target chromosome ends is not
      understood. Here, we focused on the telomeric element HeT-A and characterized the
      cell cycle expression and cytological distribution of its protein and RNA
      products. We determined the timing of telomere replication by creating a single
      lacO-marked telomere and provide evidence suggesting that transposon expression
      and recruitment to telomeres is linked to telomere replication. The HeT-A-encoded
      ORF1p protein is expressed predominantly in S phase, particularly in early S
      phase. Orf1p binds HeT-A transcripts and forms spherical structures at telomeres
      undergoing DNA replication. HeT-A sphere formation requires Verrocchio, a
      putative homolog of the conserved Stn1 telomeric protein. Our results suggest
      that coupling of telomere elongation and telomere replication is a universal
      feature, and raise the possibility that transposon recruitment to Drosophila
      telomeres is mechanistically related to telomerase recruitment in other
      organisms. Our study also supports a co-adaptive relationship between the
      Drosophila host and HeT-A mobile elements.

PMID- 24733843
TI  - The human immune system recognizes neopeptides derived from mitochondrial DNA
      deletions.
AB  - Mutations in mitochondrial (mt) DNA accumulate with age and can result in the
      generation of neopeptides. Immune surveillance of such neopeptides may allow
      suboptimal mitochondria to be eliminated, thereby avoiding mt-related diseases,
      but may also contribute to autoimmunity in susceptible individuals. To date, the
      direct recognition of neo-mtpeptides by the adaptive immune system has not been
      demonstrated. In this study we used bioinformatics approaches to predict MHC
      binding of neopeptides identified from known deletions in mtDNA. Six such
      peptides were confirmed experimentally to bind to HLA-A*02. Pre-existing human
      CD4(+) and CD8(+) T cells from healthy donors were shown to recognize and respond
      to these neopeptides. One remarkably promiscuous immunodominant peptide (P9)
      could be presented by diverse MHC molecules to CD4(+) and/or CD8(+) T cells from
      75% of the healthy donors tested. The common soil microbe, Bacillus pumilus,
      encodes a 9-mer that differs by one amino acid from P9. Similarly, the ATP
      synthase F0 subunit 6 from normal human mitochondria encodes a 9-mer with a
      single amino acid difference from P9 with 89% homology to P9. T cells expanded
      from human PBMCs using the B. pumilus or self-mt peptide bound to P9/HLA-A2
      tetramers, arguing for cross-reactivity between T cells with specificity for self
      and foreign homologs of the altered mt peptide. These findings provide proof of
      principal that the immune system can recognize peptides arising from spontaneous
      somatic mutations and that such responses might be primed by foreign peptides
      and/or be cross-reactive with self. 

PMID- 24733844
TI  - Pseudomonas aeruginosa-induced apoptosis in airway epithelial cells is mediated
      by gap junctional communication in a JNK-dependent manner.
AB  - Chronic infection and inflammation of the airways is a hallmark of cystic
      fibrosis (CF), a disease caused by mutations in the CF transmembrane conductance
      regulator (CFTR) gene. The response of the CF airway epithelium to the
      opportunistic pathogen Pseudomonas aeruginosa is characterized by altered
      inflammation and apoptosis. In this study, we examined innate immune recognition
      and epithelial responses at the level of the gap junction protein connexin43
      (Cx43) in polarized human airway epithelial cells upon infection by PAO1. We
      report that PAO1 activates cell surface receptors to elicit an intracellular
      signaling cascade leading to enhancement of gap junctional communication.
      Expression of Cx43 involved an opposite regulation exerted by JNK and p38 MAPKs.
      PAO1-induced apoptosis was increased in the presence of a JNK inhibitor, but
      latter effect was prevented by lentiviral expression of a Cx43-specific short
      hairpin RNA. Moreover, we found that JNK activity was upregulated by
      pharmacological inhibition of CFTR in Calu-3 cells, whereas correction of a CF
      airway cell line (CF15 cells) by adenoviral expression of CFTR reduced the
      activation of this MAPK. Interestingly, CFTR inhibition in Calu-3 cells was
      associated with decreased Cx43 expression and reduced apoptosis. These results
      indicate that Cx43 expression is a component of the response of airway epithelial
      cells to innate immune activation by regulating the survival/apoptosis balance.
      Defective CFTR could alter this equilibrium with deleterious consequences on the
      CF epithelial response to P. aeruginosa. 

PMID- 24733845
TI  - Maturation of innate responses to mycobacteria over the first nine months of
      life.
AB  - Newborns and young infants are particularly susceptible to infections, including
      Mycobacterium tuberculosis. Further, immunogenicity of vaccines against
      tuberculosis and other infectious diseases appears suboptimal early in life
      compared with later in life. We hypothesized that developmental changes in innate
      immunity would underlie these observations. To determine the evolution of innate
      responses to mycobacteria early in life, whole blood or PBMC from newborns, as
      well as 10- and 36-wk-old infants, was incubated with viable Mycobacterium bovis
      bacillus Calmette-Guerin or TLR ligands. Innate cell expression of cytokines and
      maturation markers was assessed, as well as activation of the proinflammatory NF
      kappaB- and MAPK-signaling pathways. Bacillus Calmette-Guerin-induced production
      of the proinflammatory cytokines TNF-alpha, IL-6, and IL-12p40 increased from the
      newborn period to 9 mo of age in monocytes but not in myeloid dendritic cells. No
      changes in production of anti-inflammatory IL-10 were observed. CD40 expression
      increased with age in both cell populations. Older infants displayed substantial
      activation of all three signal transduction molecules: degradation of NF-kappaB
      inhibitor IkappaBalpha and phosphorylation of MAPK Erk and p38 upon TLR1/2
      triggering, compared with predominant activation of only one of any of these
      molecules in newborns. Maturation of innate proinflammatory responses during the
      first 9 mo of life may underlie more effective control of mycobacteria and other
      pathogens observed later in infancy and age-related differential induction of Th1
      responses by vaccination. 

PMID- 24733846
TI  - The very low density lipoprotein receptor attenuates house dust mite-induced
      airway inflammation by suppressing dendritic cell-mediated adaptive immune
      responses.
AB  - The very low density lipoprotein receptor (VLDLR) is a member of the low-density
      lipoprotein receptor family that binds multiple ligands and plays a key role in
      brain development. Although the VLDLR mediates pleiotropic biological processes,
      only a limited amount of information is available regarding its role in adaptive
      immunity. In this study, we identify an important role for the VLDLR in
      attenuating house dust mite (HDM)-induced airway inflammation in experimental
      murine asthma. We show that HDM-challenged Vldlr(-/-) mice have augmented
      eosinophilic and lymphocytic airway inflammation with increases in Th2 cytokines,
      C-C chemokines, IgE production, and mucous cell metaplasia. A genome-wide
      analysis of the lung transcriptome identified that mRNA levels of CD209e (DC
      SIGNR4), a murine homolog of DC-SIGN, were increased in the lungs of HDM
      challenged Vldlr(-/-) mice, which suggested that the VLDLR might modify dendritic
      cell (DC) function. Consistent with this, VLDLR expression by human monocyte
      derived DCs was increased by HDM stimulation. In addition, 55% of peripheral
      blood CD11c(+) DCs from individuals with allergy expressed VLDLR under basal
      conditions. Lastly, the adoptive transfer of HDM-pulsed, CD11c(+) bone marrow
      derived DCs (BMDCs) from Vldlr(-/-) mice to the airways of wild type recipient
      mice induced augmented eosinophilic and lymphocytic airway inflammation upon HDM
      challenge with increases in Th2 cytokines, C-C chemokines, IgE production, and
      mucous cell metaplasia, as compared with the adoptive transfer of HDM-pulsed,
      CD11c(+) BMDCs from wild type mice. Collectively, these results identify a novel
      role for the VLDLR as a negative regulator of DC-mediated adaptive immune
      responses in HDM-induced allergic airway inflammation. 

PMID- 24733847
TI  - Conversion of Der p 23, a new major house dust mite allergen, into a
      hypoallergenic vaccine.
AB  - Der p 23, a new, major house dust mite (HDM) allergen that is recognized by >70%
      of HDM-allergic patients, has high allergenic activity and, therefore, must be
      considered an important component for HDM-specific immunotherapy. We constructed
      and characterized a hypoallergenic Der p 23 vaccine for HDM immunotherapy. Three
      nonallergenic peptides from the C-terminal IgE epitope-containing part of Der p
      23 (P4, P5) and P6, a mutant peptide containing serines instead of cysteines,
      were identified. Peptides were fused to the hepatitis B virus-derived PreS domain
      as recombinant fusion proteins (i.e., PreS-2XP4P5 and PreS-4XP6) that were
      expressed in Escherichia coli and purified to homogeneity. Compared with Der p
      23, PreS-2XP4P5 and PreS-4XP6 showed no relevant IgE reactivity and exhibited
      considerably reduced allergenic activity in basophil activation tests using blood
      from HDM-allergic patients. Upon immunization of rabbits, only PreS-2XP4P5
      induced high levels of Der p 23-specific IgG Abs that inhibited binding of
      patients' IgE to Der p 23, comparable to IgG Abs induced with Der p 23, whereas
      Abs induced with PreS-4XP6 had only low blocking capacity. Additionally, IgG Abs
      induced with PreS-2XP4P5 inhibited Der p 23-induced basophil activation
      comparable to IgG Abs induced with Der p 23. Compared with Der p 23, PreS-2XP4P5
      induced lower T cell proliferation but higher levels of the tolerogenic cytokine
      IL-10 and the Th1 cytokine IFN-gamma in PBMCs from HDM-allergic patients,
      indicating an immunomodulatory capacity of the fusion protein. Therefore, PreS
      2XP4P5 represents a promising candidate for immunotherapy of HDM-allergic
      patients. 

PMID- 24733848
TI  - Bromodomain and extraterminal proteins suppress NF-E2-related factor 2-mediated
      antioxidant gene expression.
AB  - Oxidative stress, a pathogenetic factor in many conditions, including chronic
      obstructive pulmonary disease, arises due to accumulation of reactive oxygen
      species and defective antioxidant defenses in the lungs. The latter is due, at
      least in part, to impaired activation of NF-E2-related factor 2 (Nrf2), a
      transcription factor involved in the activation of antioxidant and cytoprotective
      genes. The bromodomain and extraterminal (BET) proteins, Brd2, Brd3, Brd4, and
      BrdT, bind to acetylated lysine residues on histone or nonhistone proteins
      recruiting transcriptional regulators and thus activating or repressing gene
      transcription. We investigated whether BET proteins modulate the regulation of
      Nrf2-dependent gene expression in primary human airway smooth muscle cells and
      the human monocytic cell line, THP-1. Inhibition of BET protein bromodomains
      using the inhibitor JQ1+ or attenuation of Brd2 and Brd4 expression using small
      interfering RNA led to activation of Nrf2-dependent transcription and expression
      of the antioxidant proteins heme oxygenase-1, NADPH quinone oxidoreductase 1, and
      glutamate-cysteine ligase catalytic subunit. Also, JQ1+ prevented H2O2-induced
      intracellular reactive oxygen species production. By coimmunoprecipitation, BET
      proteins were found to be complexed with Nrf2, whereas chromatin
      immunoprecipitation studies indicated recruitment of Brd2 and Brd4 to Nrf2
      binding sites on the promoters of heme oxygenase-1 and NADPH quinone
      oxidoreductase 1. BET proteins, particularly Brd2 and Brd4, may play a key role
      in the regulation of Nrf2-dependent antioxidant gene transcription and are hence
      an important target for augmenting antioxidant responses in oxidative stress
      mediated diseases. 

PMID- 24733849
TI  - SHP2 phosphatase promotes mast cell chemotaxis toward stem cell factor via
      enhancing activation of the Lyn/Vav/Rac signaling axis.
AB  - SHP2 protein-tyrosine phosphatase (encoded by Ptpn11) positively regulates KIT
      (CD117) signaling in mast cells and is required for mast cell survival and
      homeostasis in mice. In this study, we uncover a role of SHP2 in promoting
      chemotaxis of mast cells toward stem cell factor (SCF), the ligand for KIT
      receptor. Using an inducible SHP2 knockout (KO) bone marrow-derived mast cell
      (BMMC) model, we observed defects in SCF-induced cell spreading, polarization,
      and chemotaxis. To address the mechanisms involved, we tested whether SHP2
      promotes activation of Lyn kinase that was previously shown to promote mast cell
      chemotaxis. In SHP2 KO BMMCs, SCF-induced phosphorylation of the inhibitory C
      terminal residue (pY507) was elevated compared with control cells, and
      phosphorylation of activation loop (pY396) was diminished. Because Lyn also was
      detected by substrate trapping assays, these results are consistent with SHP2
      activating Lyn directly by dephosphorylation of pY507. Further analyses revealed
      a SHP2- and Lyn-dependent pathway leading to phosphorylation of Vav1, Rac
      activation, and F-actin polymerization in SCF-treated BMMCs. Treatment of BMMCs
      with a SHP2 inhibitor also led to impaired chemotaxis, consistent with SHP2
      promoting SCF-induced chemotaxis of mast cells via a phosphatase-dependent
      mechanism. Thus, SHP2 inhibitors may be useful to limit SCF/KIT-induced mast cell
      recruitment to inflamed tissues or the tumor microenvironment. 

PMID- 24733851
TI  - Progression-free survival: too much risk, not enough reward?

PMID- 24733850
TI  - A biased non-Galphai OXE-R antagonist demonstrates that Galphai protein subunit
      is not directly involved in neutrophil, eosinophil, and monocyte activation by 5
      oxo-ETE.
AB  - Galphai-coupled chemoattractant receptors, such as the 5-oxo-6E,8Z,11Z,14Z
      eicosatetraenoic acid (5-oxo-ETE) receptor (OXE-R), are able to switch on
      Galphaibetagamma protein-dependent and beta-arrestin-related signaling traits.
      However, which of these signaling pathways are truly important for the
      chemoattractant functions in leukocytes is not clarified yet. As we recently
      reported, Gue1654 is a unique Gbetagamma-biased OXE-R antagonist having no
      inhibitory activity on Galphai-related signaling, which makes Gue1654 an
      unprecedented tool for assessing the involvement of G protein subunits in
      chemoattractant receptor function. beta-arrestin2 recruitment was studied in OXE
      R-overexpressing HEK293 cells using bioluminescence resonance energy transfer
      assays. Activation of leukocytes was assessed by flow cytometric assays and by
      immunofluorescence microscopy. Leukocyte capture to endothelial cells was
      addressed under physiological flow conditions. We found that Gue1654 blocks beta
      arrestin2 recruitment in HEK293 cells overexpressing OXE-R and ERK1/2
      phosphorylation in human eosinophils and neutrophils. Furthermore, Gue1654 was
      able to prevent several 5-oxo-ETE-triggered functional events in eosinophils and
      neutrophils, such as activation of CD11b/CD18 integrins, oxidative burst, actin
      polymerization, and interaction with endothelial cells. In addition, Gue1654
      completely prevented 5-oxo-ETE-induced Ca(2+) flux and chemotaxis of human
      primary monocytes. All of these leukocyte responses to 5-oxo-ETE, except ERK1/2
      phosphorylation and oxidative burst, were likewise prevented by pertussis toxin.
      Therefore, we conclude that chemoattractant receptors require Galphai subunits
      only as adaptors to transactivate the Gbetagamma heteromers, which then act
      responsible for cell activation. Finally, our data characterize Gue1654 as a non
      Galphai-biased antagonist of OXE-R that provides a new basis for therapeutic
      intervention in inflammatory diseases that involve activation of eosinophils,
      neutrophils, and monocytes. 

PMID- 24733853
TI  - Bevacizumab treatment for human glioblastoma. Can it induce cognitive impairment?
AB  - Recent results from 2 double-blind, placebo-controlled phase III trials (RTOG
      0825) and (AVAglio) for first-line treatment of glioblastoma patients with the
      VEGF antibody bevacizumab, showed similar results, related to overall and
      progression-free survival. The RTOG 0825 trial indicated, opposed to the AVAglio
      trial, that patients treated with bevacizumab showed a decline in global
      neurocognitive function compared to untreated patients, -a decline that was most
      obvious after prolonged treatment. At present, there is a considerably
      controversy related to these observations. In the present work we point at the
      possibility that bevacizumab treatment of the normal brain can reduce synaptic
      plasticity in the hippocampus. We believe that such a phenomenon may partly
      explain the reduced cognitive function observed in patients in the RTOG 0825
      trial. Since the same effects were not clearly defined in the AVAglio trial,
      further studies on putative neurocognitive effects after bevacizumab treatment
      are warranted. 

PMID- 24733854
TI  - Is there a role for vaccine-based therapy in recurrent glioblastoma?

PMID- 24733857
TI  - Remote spinal cord injury in mucopolysaccharidosis type IVA after cervical
      decompression.
AB  - Morquio A syndrome (Online Mendelian Inheritance in Man #253000) is a lysosomal
      storage disease caused by deficiency of N-acetylgalactosamine-6-sulfatase encoded
      by the GALNS gene. Key clinical features are skeletal dysplasia and short
      stature. 

PMID- 24733858
TI  - Evolution of mild cognitive impairment in Parkinson disease.

PMID- 24733859
TI  - Risk factors for dementia with Lewy bodies: a case-control study.

PMID- 24733860
TI  - Incidence and prevalence of small-fiber neuropathy: a survey in the Netherlands.

PMID- 24733862
TI  - Clinical reasoning: a 49-year-old woman with progressive motor deficit.
AB  - A previously healthy 49-year-old woman presented with progressive motor deficit.
      The complaints started the year before with weakness of the right arm. Over the
      subsequent months, she developed weakness in the left arm, followed by both legs,
      and, finally, difficulty speaking, with nasal voice, and swallowing. It was
      increasingly difficult to attend to her chores, and, by the time she sought
      medical attention, she needed help with all daily activities. In the last few
      weeks, she also complained of diffuse joint and muscle pain. Medical and family
      history were unremarkable. 

PMID- 24733863
TI  - Clinical reasoning: acute-onset homonymous hemianopia with hyperglycemia: seeing
      is believing.
AB  - A 32-year-old woman with a history of bipolar disorder, polycystic ovarian
      syndrome, and hypertension and a 4-year history of uncontrolled type 2 diabetes
      mellitus (DM) presented with bifrontal headache, elevated blood sugars (>500
      mg/dL), and abrupt-onset left homonymous hemianopia upon awakening. Vital signs
      included temperature 98.0 degrees F, blood pressure 160/89 mm Hg, and heart rate
      67 bpm. Neurologic examination showed dense left homonymous hemianopia with
      macular sparing and without other focal findings. 

PMID- 24733864
TI  - Teaching neuroimages: carotid-cavernous fistula caused by fibromuscular
      dysplasia.
AB  - A 26-year-old woman developed headache, diplopia, and pulsatile tinnitus in 10
      days. Neurologic examination revealed limitation of left eye movement, left
      dilated pupil with optic disc swelling and mild decreased vision, and a bruit
      over the left superior orbit. Her family history, laboratory data, and cerebral
      MRI showed normal findings. Cerebral CT angiography suggested left carotid
      cavernous fistula (CCF). Follow-up angiography confirmed left CCF (figure 1).
      Nevertheless, multiple stenoses interspersed with aneurysmal dilation segments of
      carotid, vertebral, and renal arteries were found (figure 2). A diagnosis of
      fibromuscular dysplasia (FMD) was finally made. FMD is a rare cause of CCF.(1,2.)

PMID- 24733865
TI  - Transcriptome comparison of global distinctive features between pollination and
      parthenocarpic fruit set reveals transcriptional phytohormone cross-talk in
      cucumber (Cucumis sativus L.).
AB  - Parthenocarpy is an important trait determining yield and quality of fruit crops.
      However, the understanding of the mechanisms underlying parthenocarpy induction
      is limited. Cucumber (Cucumis sativus L.) is abundant in parthenocarpic germplasm
      resources and is an excellent model organism for parthenocarpy studies. In this
      study, the transcriptome of cucumber fruits was studied using RNA sequencing (RNA
      Seq). Differentially expressed genes (DEGs) of set fruits were compared against
      aborted fruits. Distinctive features of parthenocarpic and pollinated fruits were
      revealed by combining the analysis of the transcriptome together with
      cytomorphological and physiological analysis. Cell division and the transcription
      of cell division genes were found to be more active in parthenocarpic fruit. The
      study also indicated that parthenocarpic fruit set is a high sugar-consuming
      process which is achieved via enhanced carbohydrate degradation through
      transcription of genes that lead to the breakdown of carbohydrates. Furthermore,
      the evidence provided by this work supports a hypothesis that parthenocarpic
      fruit set is induced by mimicking the processes of pollination/fertilization at
      the transcriptional level, i.e. by performing the same transcriptional patterns
      of genes inducing pollination and gametophyte development as in pollinated fruit.
      Based on the RNA-Seq and ovary transient expression results, 14 genes were
      predicted as putative parthenocarpic genes. The transcription analysis of these
      candidate genes revealed auxin, cytokinin and gibberellin cross-talk at the
      transcriptional level during parthenocarpic fruit set. 

PMID- 24733867
TI  - Technology-enhanced simulation and pediatric education: a meta-analysis.
AB  - BACKGROUND AND OBJECTIVE: Pediatrics has embraced technology-enhanced simulation
      (TES) as an educational modality, but its effectiveness for pediatric education
      remains unclear. The objective of this study was to describe the characteristics
      and evaluate the effectiveness of TES for pediatric education. METHODS: This
      review adhered to PRISMA (Preferred Reporting Items for Systematic Reviews and
      Meta-Analyses) standards. A systematic search of Medline, Embase, CINAHL, ERIC,
      Web of Science, Scopus, key journals, and previous review bibliographies through
      May 2011 and an updated Medline search through October 2013 were conducted.
      Original research articles in any language evaluating the use of TES for
      educating health care providers at any stage, where the content solely focuses on
      patients 18 years or younger, were selected. Reviewers working in duplicate
      abstracted information on learners, clinical topic, instructional design, study
      quality, and outcomes. We coded skills (simulated setting) separately for time
      and nontime measures and similarly classified patient care behaviors and patient
      effects. RESULTS: We identified 57 studies (3666 learners) using TES to teach
      pediatrics. Effect sizes (ESs) were pooled by using a random-effects model. Among
      studies comparing TES with no intervention, pooled ESs were large for outcomes of
      knowledge, nontime skills (eg, performance in simulated setting), behaviors with
      patients, and time to task completion (ES = 0.80-1.91). Studies comparing the use
      of high versus low physical realism simulators showed small to moderate effects
      favoring high physical realism (ES = 0.31-0.70). CONCLUSIONS: TES for pediatric
      education is associated with large ESs in comparison with no intervention. Future
      research should include comparative studies that identify optimal instructional
      methods and incorporate pediatric-specific issues into educational interventions.

PMID- 24733866
TI  - Baroreflex failure, sympathetic storm, and cerebral vasospasm in fibulin-4 cutis
      laxa.
AB  - Sudden, severe, and life-threatening, the crises associated with baroreflex
      failure are diagnostically challenging, particularly in children, a population in
      which it has rarely been described. The baroreflex failure syndrome results from
      impaired afferent baroreceptive input and manifests with autonomic stimulation
      induced surges in blood pressure and heart rate accompanied by distinct signs,
      including thunderclap headache, diaphoresis, and emotional instability. Although
      the adult literature includes cases of severe headache in baroreflex failure,(1)
      (,) (2) we present the first case of a child with recurrent thunderclap headache
      and cerebral vasospasm with baroreflex failure secondary to vascular
      complications of a rare genetic connective tissue disorder. 

PMID- 24733868
TI  - Infant self-regulation and early childhood media exposure.
AB  - OBJECTIVES: Examine prospective associations between parent-reported early
      childhood self-regulation problems and media exposure (television and video
      viewing) at 2 years. We hypothesized that children with poor self-regulation
      would consume more media, possibly as a parent coping strategy. METHODS: We used
      data from 7450 children in the Early Childhood Longitudinal Study-Birth Cohort.
      When children were 9 months and 2 years old, parents completed the Infant Toddler
      Symptom Checklist (ITSC), a validated scale of self-regulation. With daily media
      use at 2 years as our outcome, we conducted weighted multivariable regression
      analyses, controlling for child, maternal, and household characteristics.
      RESULTS: Children watched an average of 2.3 hours per day (SD 1.9) of media at
      age 2 years. Infants with poor self-regulation (9-month ITSC score >=3) viewed
      0.23 hour per day (95% confidence interval [CI] 0.12-0.35) more media at 2 years
      compared with those with 9-month ITSC score of 0 to 2; this remained significant
      in adjusted models (0.15 hour per day [95% CI 0.02-0.28]). Children rated as
      having persistent self-regulation problems (ITSC >=3 at both 9 months and 2
      years) were even more likely to consume media at age 2 (adjusted beta 0.21 hour
      per day [95% CI 0.03-0.39]; adjusted odds ratio for >2 hours per day 1.40 [95% CI
      1.14-1.71]). These associations were slightly stronger in low socioeconomic
      status and English-speaking households. CONCLUSIONS: Early childhood self
      regulation problems are associated with mildly increased media exposure, even
      after controlling for important confounding variables. Understanding this
      relationship may provide insight into helping parents reduce their children's
      screen time.

PMID- 24733870
TI  - Marking the path forward with milestones.

PMID- 24733869
TI  - Social media methods for studying rare diseases.
AB  - For pediatric rare diseases, the number of patients available to support
      traditional research methods is often inadequate. However, patients who have
      similar diseases cluster "virtually" online via social media. This study aimed to
      (1) determine whether patients who have the rare diseases Fontan-associated
      protein losing enteropathy (PLE) and plastic bronchitis (PB) would participate in
      online research, and (2) explore response patterns to examine social media's role
      in participation compared with other referral modalities. A novel, internet-based
      survey querying details of potential pathogenesis, course, and treatment of PLE
      and PB was created. The study was available online via web and Facebook portals
      for 1 year. Apart from 2 study-initiated posts on patient-run Facebook pages at
      the study initiation, all recruitment was driven by study respondents only.
      Response patterns and referral sources were tracked. A total of 671 respondents
      with a Fontan palliation completed a valid survey, including 76 who had PLE and
      46 who had PB. Responses over time demonstrated periodic, marked increases as new
      online populations of Fontan patients were reached. Of the responses, 574 (86%)
      were from the United States and 97 (14%) were international. The leading referral
      sources were Facebook, internet forums, and traditional websites. Overall, social
      media outlets referred 84% of all responses, making it the dominant modality for
      recruiting the largest reported contemporary cohort of Fontan patients and
      patients who have PLE and PB. The methodology and response patterns from this
      study can be used to design research applications for other rare diseases. 

PMID- 24733871
TI  - Postmarketing trials and pediatric device approvals.
AB  - BACKGROUND: Medical devices can be useful in a variety of diseases, but few
      devices have been specifically approved for use in children. The 2007 Pediatric
      Medical Device Safety and Improvement Act was passed to stimulate pediatric
      device development. The current state of trial evidence underpinning the approval
      of pediatric devices remains poorly described. METHODS: We identified all high
      risk (ie, class III) devices approved through the premarket approval or
      humanitarian device exemption pathways for therapeutic use in children between
      2008 and 2011. We collected key information on clinical trial design
      (randomization, blinding, controls, and types of end points) as well as age
      distribution of trial participants. We also identified US Food and Drug
      Administration (FDA)-mandated postmarketing trials. RESULTS: Twenty-two devices
      were approved for use in children via the premarket approval pathway and 3 via
      the humanitarian device exemption pathway. Twenty-two (88%) qualified as
      pediatric despite minimum approval ages of >=18 years (the FDA Center for Devices
      and Radiologic Health considers patients 18-21 years old as pediatric). Most
      devices were approved on the basis of nonrandomized (59%), open-label (68%)
      studies with surrogate effectiveness end points (86%). Overall, 21 (84%) devices
      were not studied in any patients <18 years of age. Postmarketing studies were
      mandated by the FDA for 19 (76%) devices, although only 3 (18%) required
      enrollment of pediatric patients. CONCLUSIONS: Most high-risk pediatric devices
      are approved on the basis of trials in patients >=18 years old, with few
      pediatric patients exposed to the devices before market availability. Few
      postmarketing studies require additional study in pediatric patients.

PMID- 24733872
TI  - Injury among children and young adults with epilepsy.
AB  - OBJECTIVE: To investigate whether children and young adults with epilepsy are at
      a greater risk of fracture, thermal injury, or poisoning than those without.
      METHODS: A cohort study was conducted by using the Clinical Practice Research
      Datalink (1987-2009), a longitudinal database containing primary care records. A
      total of 11 934 people with epilepsy and 46 598 without, aged between 1 and 24
      years at diagnosis, were followed for a median (interquartile range) of 2.6 (0.8
      5.9) years. The risk of fractures (including long bone fractures), thermal
      injuries, and poisonings (including medicinal and nonmedicinal poisonings) was
      estimated. RESULTS: Adjusting for age, gender, Strategic Health Authority region,
      deprivation, and calendar year at study entry (and, for medicinal poisonings,
      behavior disorder), people with epilepsy had an 18% increase in risk of fracture
      (hazard ratio [HR] = 1.18; 95% confidence interval [CI], 1.09-1.27), a 23%
      increase in risk of long bone fracture (HR = 1.23; 95% CI, 1.10-1.38), a 49%
      increase in risk of thermal injury (HR = 1.49; 95% CI, 1.27-1.75), and more than
      twice the risk of poisoning (HR = 2.47; 95% CI, 2.15-2.84), which was limited to
      poisoning from medicinal products (medicinal HR = 2.54; 95% CI, 2.16-2.99;
      nonmedicinal HR = 0.96; 95% CI, 0.61-1.52). CONCLUSIONS: Children and young
      adults with epilepsy are at a greater risk of fracture, thermal injury, and
      poisoning than those without. The greatest risk is from medicinal poisonings.
      Doctors and other health care professionals should provide injury and poison
      prevention advice at diagnosis and epilepsy reviews.

PMID- 24733873
TI  - Putting the pediatrics milestones into practice: a consensus roadmap and resource
      analysis.
AB  - The Accreditation Council for Graduate Medical Education has partnered with
      member boards of the American Board of Medical Specialties to initiate the next
      steps in advancing competency-based assessment in residency programs. This
      initiative, known as the Milestone Project, is a paradigm shift from traditional
      assessment efforts and requires all pediatrics residency programs to report
      individual resident progression along a series of 4 to 5 developmental levels of
      performance, or milestones, for individual competencies every 6 months beginning
      in June 2014. The effort required to successfully make this shift is tremendous
      given the number of training programs, training institutions, and trainees.
      However, it holds great promise for achieving training outcomes that align with
      patient needs; developing a valid, reliable, and meaningful way to track
      residents' development; and providing trainees with a roadmap for learning.
      Recognizing the resources needed to implement this new system, the authors, all
      residency program leaders, provide their consensus view of the components
      necessary for implementing and sustaining this effort, including resource
      estimates for completing this work. The authors have identified 4 domains: (1)
      Program Review and Development of Stakeholders and Participants, (2) Assessment
      Methods and Validation, (3) Data and Assessment System Development, and (4)
      Summative Assessment and Feedback. This work can serve as a starting point and
      framework for collaboration with program, department, and institutional leaders
      to identify and garner necessary resources and plan for local and national
      efforts that will ensure successful transition to milestones-based assessment. 

PMID- 24733874
TI  - Writing medical student and resident performance evaluations: beyond "performed
      as expected".

PMID- 24733875
TI  - Pain insensitivity syndrome misinterpreted as inflicted burns.
AB  - We present a case study of a 10-year-old child with severe burns that were
      misinterpreted as inflicted burns. Because of multiple injuries since early life,
      the family was under suspicion of child abuse and therefore under supervision of
      the Child Care Board for 2 years before the boy was burned. Because the boy
      incurred the burns without feeling pain, we conducted a thorough medical
      examination and laboratory testing, evaluated detection and pain thresholds, and
      used MRI to study brain morphology and brain activation patterns during pain
      between this patient and 3 healthy age- and gender-matched controls. We found
      elevated detection and pain thresholds and lower brain activation during pain in
      the patient compared with the healthy controls and reference values. The patient
      received the diagnosis of hereditary sensory and autonomic neuropathy type IV on
      the basis of clinical findings and the laboratory testing, complemented with the
      altered pain and detection thresholds and MRI findings. Hereditary sensory and
      autonomic neuropathy IV is a very rare congenital pain insensitivity syndrome
      characterized by the absence of pain and temperature sensation combined with oral
      mutilation due to unawareness, fractures, and anhidrosis caused by abnormalities
      in the peripheral nerves. Health care workers should be aware of the potential
      presence of this disease to prevent false accusations of child abuse. 

PMID- 24733876
TI  - Variations in measurement of sexual activity based on EHR definitions.
AB  - OBJECTIVE: The goal of this study was to compare the performance of 4 operational
      definitions of sexual activity by using data electronically abstracted from
      electronic health records (EHRs) and examine how documentation of Chlamydia
      screening and positivity vary according to definition of sexual activity.
      METHODS: Extracts were created from EHRs of adolescent females 12 to 19 years old
      who had >=1 visit to a primary care practice during 2011 at 4 US pediatric health
      care organizations. We created 4 definitions of sexual activity derived from
      electronically abstracted indicator variables. Percent sexually active,
      documentation of Chlamydia screening, and rate of positive Chlamydia test results
      per 1000 adolescent females according to the sexual activity definition were
      calculated. RESULTS: The most commonly documented individual indicator of sexual
      activity was "patient report of being sexually active" (mean across 4 sites:
      19.2%). The percentage of adolescent females classified as sexually active varied
      by site and increased as more indicator variables were included. As the
      definition of sexual activity expanded, the percentage of sexually active females
      who received at least 1 Chlamydia test decreased. Using a broader definition of
      sexual activity resulted in improved identification of adolescent females with
      Chlamydia infection. For each sexual activity definition and performance item,
      the difference was statistically significant (P < .0001). CONCLUSIONS:
      Information about sexual activity may be gathered from a variety of data sources,
      and changing the configurations of these indicators results in differences in the
      percentage of adolescent females classified as sexually active, screened for
      Chlamydia infection, and Chlamydia infection rates.

PMID- 24733877
TI  - A longitudinal study of paternal mental health during transition to fatherhood as
      young adults.
AB  - BACKGROUND AND OBJECTIVE: Rates of paternal depression range from 5% to 10% with
      a growing body of literature describing the harm to fathers, children, and
      families. Changes in depression symptoms over the life course, and the role of
      social factors, are not well known. This study examines associations with changes
      in depression symptoms during the transition to fatherhood for young fathers and
      whether this association differed by key social factors. METHODS: We combined all
      4 waves of the National Longitudinal Study of Adolescent Health to support a 23
      year longitudinal analysis of 10 623 men and then created a "fatherhood-year"
      data set, regressing age-adjusted standardized depressive symptoms scores on
      fatherhood status (nonresidence/residence), fatherhood-years, and covariates to
      determine associations between Center for Epidemiologic Studies Depression Scale
      scores and fatherhood life course intervals. RESULTS: Depressive symptom scores
      reported at the entry into fatherhood are higher for nonresident fathers than
      nonfathers, which in turn are higher than those of resident fathers. Resident
      fathers have a significant decrease in scores during late adolescence (beta = 
      0.035, P = .023), but a significant increase in scores during early fatherhood
      (beta = 0.023, P = .041). From entrance into fatherhood to the end of early
      fatherhood (+5 years), the depressive symptoms score for resident fathers
      increases on average by 68%. CONCLUSIONS: In our longitudinal, population-based
      study, resident fathers show increasing depressive symptom scores during
      children's key attachment years of 0-5. Identifying at-risk fathers based on
      social factors and designing effective interventions may ultimately improve
      health outcomes for the entire family.

PMID- 24733878
TI  - Television viewing, bedroom television, and sleep duration from infancy to mid
      childhood.
AB  - BACKGROUND: Television and insufficient sleep are associated with poor mental and
      physical health. This study assessed associations of TV viewing and bedroom TV
      with sleep duration from infancy to midchildhood. METHOD: We studied 1864
      children in Project Viva. Parents reported children's average daily TV viewing
      and sleep (at 6 months and annually from 1-7 years) and the presence of a bedroom
      TV (annually 4-7 years). We used mixed effects models to assess associations of
      TV exposures with contemporaneous sleep, adjusting for child age, gender,
      race/ethnicity, maternal education, and income. RESULTS: Six hundred forty-three
      children (35%) were racial/ethnic minorities; 37% of households had incomes <=$70
      000. From 6 months to 7 years, mean (SD) sleep duration decreased from 12.2 (2.0)
      hours to 9.8 (0.9) hours per day; TV viewing increased from 0.9 (1.2) hours to
      1.6 (1.0) hours per day. At 4 years, 17% had a bedroom TV, rising to 23% at 7
      years. Each 1 hour per day increase in lifetime TV viewing was associated with 7
      minutes per day (95% confidence interval [CI]: 4 to 10) shorter sleep. The
      association of bedroom TV varied by race/ethnicity; bedroom TV was associated
      with 31 minutes per day shorter sleep (95% CI: 16 to 45) among racial/ethnic
      minority children, but not among white, non-Hispanic children (8 fewer minutes
      per day [95% CI: -19 to 2]). CONCLUSIONS: More TV viewing, and, among
      racial/ethnic minority children, the presence of a bedroom TV, were associated
      with shorter sleep from infancy to midchildhood.

PMID- 24733879
TI  - Childhood sexual abuse and suicidal behavior: a meta-analysis.
AB  - BACKGROUND AND OBJECTIVE: Self-inflicted injuries are one of the major causes of
      disease burden and death globally. Understanding the extent to which this is
      associated with childhood sexual abuse (CSA) exposure can help inform prevention
      strategies. We aimed to quantify to what extent CSA was associated with incident
      suicide attempts in men and women. METHODS: We searched 20 health and social
      science databases from first record until February 2009 and updated the search in
      Medline from February 2009 to February 1, 2013. Longitudinal studies and cotwin
      analyses from twin studies in any population from any year were eligible for
      inclusion. Of 22 235 abstracts screened as part of a series of reviews, 9 studies
      met the inclusion criteria for this review. Characteristics, effect estimates,
      and quality data were extracted. Random-effects meta-analysis was used to
      generate pooled odds ratios (ORs). RESULTS: Seven longitudinal and 2 twin studies
      with 8733 participants met the inclusion criteria. The overall pooled estimate
      for longitudinal studies was OR = 2.43 (95% confidence interval: 1.94-3.05), I(2)
      = 87.5%, P < .0001. The pooled OR from cotwin analysis was 2.65 (95% confidence
      interval: 0.82-4.49, I(2) = 0%, P = .867). Studies adjusted for a range of
      confounders, but baseline suicidal behavior was not well-controlled. Too few
      studies met the inclusion criteria to quantitatively examine sources of
      heterogeneity. CONCLUSIONS: CSA exposure is associated with suicide attempts when
      a range of different confounders are controlled for, but the temporality of the
      association is not well established, and the association is highly heterogeneous.

PMID- 24733880
TI  - Rape prevention through empowerment of adolescent girls.
AB  - BACKGROUND AND OBJECTIVE: Sexual assault is a major cause of injury, unplanned
      pregnancy, HIV infection, and mental health problems worldwide. In parts of sub
      Saharan Africa, sexual assault has reached epidemic proportions. This study
      evaluated the efficacy of an empowerment and self-defense intervention for
      adolescent girls to decrease the incidence of sexual assault and harassment in
      Nairobi's large informal settlements. METHODS: A prospective cohort of 1978
      adolescents from 4 neighborhoods near Nairobi were taught empowerment,
      deescalation, and self-defense skills in six 2-hour sessions. The standard-of
      care (SOC) group (n = 428) received a life skills class. Self-reported, anonymous
      survey data were collected at baseline and 10.5 months after intervention.
      RESULTS: Annual sexual assault rates decreased from 17.9/100 person-years at
      baseline to 11.1 at follow-up (rate ratio = 1.61; 95% confidence interval [CI],
      1.26-1.86; P < .001); there was no significant change in the SOC group (14.3 to
      14.0, rate ratio = 1.02; 95% CI, 0.67-1.57, P = .92). Sexual assault disclosure
      in the intervention group increased from 56% to 75% (P = .006), compared with a
      constant incidence of disclosure (53%) in the SOC group. The majority (52.3%) of
      adolescents in the intervention group reported using skills learned to stop an
      assault. CONCLUSIONS: This intervention decreased sexual assault rates among
      adolescent girls in Kenya. The intervention was also associated with an increase
      in the disclosure of assaults, thereby enabling survivors to seek care and
      support and possibly leading to the identification and prosecution of
      perpetrators. This model should be adaptable to other settings both in Africa and
      globally.

PMID- 24733881
TI  - Prenatal SSRI use and offspring with autism spectrum disorder or developmental
      delay.
AB  - OBJECTIVE: To examine associations between prenatal use of selective serotonin
      reuptake inhibitors (SSRIs) and the odds of autism spectrum disorders (ASDs) and
      other developmental delays (DDs). METHODS: A total of 966 mother-child pairs were
      evaluated (492 ASD, 154 DD, 320 typical development [TD]) from the Childhood
      Autism Risks from Genetics and the Environment (CHARGE) Study, a population-based
      case-control study. Standardized measures confirmed developmental status.
      Interviews with biological mothers ascertained prenatal SSRI use, maternal mental
      health history, and sociodemographic information. RESULTS: Overall, prevalence of
      prenatal SSRI exposure was lowest in TD children (3.4%) but did not differ
      significantly from ASD (5.9%) or DD (5.2%) children. Among boys, prenatal SSRI
      exposure was nearly 3 times as likely in children with ASD relative to TD
      (adjusted odds ratio [OR]: 2.91; 95% confidence interval [CI]: 1.07-7.93); the
      strongest association occurred with first-trimester exposure (OR: 3.22; 95% CI:
      1.17-8.84). Exposure was also elevated among boys with DD (OR: 3.39; 95% CI: 0.98
      11.75) and was strongest in the third trimester (OR: 4.98; 95% CI: 1.20-20.62).
      Findings were similar among mothers with an anxiety or mood disorder history.
      CONCLUSIONS: In boys, prenatal exposure to SSRIs may increase susceptibility to
      ASD or DD. Findings from published studies on SSRIs and ASD continues to be
      inconsistent. Potential recall bias and residual confounding by indication are
      concerns. Larger samples are needed to replicate DD results. Because maternal
      depression itself carries risks for the fetus, the benefits of prenatal SSRI use
      should be carefully weighed against potential harms.

PMID- 24733882
TI  - Reactive Oxygen Species-Dependent Nitric Oxide Production Contributes to Hydrogen
      Promoted Stomatal Closure in Arabidopsis.
AB  - The signaling role of hydrogen gas (H2) has attracted increasing attention from
      animals to plants. However, the physiological significance and molecular
      mechanism of H2 in drought tolerance are still largely unexplored. In this
      article, we report that abscisic acid (ABA) induced stomatal closure in
      Arabidopsis (Arabidopsis thaliana) by triggering intracellular signaling events
      involving H2, reactive oxygen species (ROS), nitric oxide (NO), and the guard
      cell outward-rectifying K+ channel (GORK). ABA elicited a rapid and sustained H2
      release and production in Arabidopsis. Exogenous hydrogen-rich water (HRW)
      effectively led to an increase of intracellular H2 production, a reduction in the
      stomatal aperture, and enhanced drought tolerance. Subsequent results revealed
      that HRW stimulated significant inductions of NO and ROS synthesis associated
      with stomatal closure in the wild type, which were individually abolished in the
      nitric reductase mutant nitrate reductase1/2 (nia1/2) or the NADPH oxidase
      deficient mutant rbohF (for respiratory burst oxidase homolog). Furthermore, we
      demonstrate that the HRW-promoted NO generation is dependent on ROS production.
      The rbohF mutant had impaired NO synthesis and stomatal closure in response to
      HRW, while these changes were rescued by exogenous application of NO. In
      addition, both HRW and hydrogen peroxide failed to induce NO production or
      stomatal closure in the nia1/2 mutant, while HRW-promoted ROS accumulation was
      not impaired. In the GORK-null mutant, stomatal closure induced by ABA, HRW, NO,
      or hydrogen peroxide was partially suppressed. Together, these results define a
      main branch of H2-regulated stomatal movement involved in the ABA signaling
      cascade in which RbohF-dependent ROS and nitric reductase-associated NO
      production, and subsequent GORK activation, were causally involved.

PMID- 24733883
TI  - Distinct Copy Number, Coding Sequence, and Locus Methylation Patterns Underlie
      Rhg1-Mediated Soybean Resistance to Soybean Cyst Nematode.
AB  - Copy number variation of kilobase-scale genomic DNA segments, beyond
      presence/absence polymorphisms, can be an important driver of adaptive traits.
      Resistance to Heterodera glycines (Rhg1) is a widely utilized quantitative trait
      locus that makes the strongest known contribution to resistance against soybean
      cyst nematode (SCN), Heterodera glycines, the most damaging pathogen of soybean
      (Glycine max). Rhg1 was recently discovered to be a complex locus at which
      resistance-conferring haplotypes carry up to 10 tandem repeat copies of a 31-kb
      DNA segment, and three disparate genes present on each repeat contribute to SCN
      resistance. Here, we use whole-genome sequencing, fiber-FISH (fluorescence in
      situ hybridization), and other methods to discover the genetic variation at Rhg1
      across 41 diverse soybean accessions. Based on copy number variation, transcript
      abundance, nucleic acid polymorphisms, and differentially methylated DNA regions,
      we find that SCN resistance is associated with multicopy Rhg1 haplotypes that
      form two distinct groups. The tested high-copy-number Rhg1 accessions, including
      plant introduction (PI) 88788, contain a flexible number of copies (seven to 10)
      of the 31-kb Rhg1 repeat. The identified low-copy-number Rhg1 group, including PI
      548402 (Peking) and PI 437654, contains three copies of the Rhg1 repeat and a
      newly identified allele of Glyma18g02590 (a predicted alpha-SNAP [alpha-soluble N
      ethylmaleimide-sensitive factor attachment protein]). There is strong evidence
      for a shared origin of the two resistance-conferring multicopy Rhg1 groups and
      subsequent independent evolution. Differentially methylated DNA regions also were
      identified within Rhg1 that correlate with SCN resistance. These data provide
      insights into copy number variation of multigene segments, using as the example a
      disease resistance trait of high economic importance.

PMID- 24733884
TI  - Arabidopsis Glutathione Transferases U24 and U25 Exhibit a Range of
      Detoxification Activities with the Environmental Pollutant and Explosive, 2,4,6
      Trinitrotoluene.
AB  - The explosive 2,4,6-trinitrotoluene (TNT) is a major worldwide military
      pollutant. The presence of this toxic and highly persistent pollutant,
      particularly at military sites and former manufacturing facilities, presents
      various health and environmental concerns. Due to the chemically resistant
      structure of TNT, it has proven to be highly recalcitrant to biodegradation in
      the environment. Here, we demonstrate the importance of two glutathione
      transferases (GSTs), GST-U24 and GST-U25, from Arabidopsis (Arabidopsis thaliana)
      that are specifically up-regulated in response to TNT exposure. To assess the
      role of GST-U24 and GST-U25, we purified and characterized recombinant forms of
      both enzymes and demonstrated the formation of three TNT glutathionyl products.
      Importantly, GST-U25 catalyzed the denitration of TNT to form 2-glutathionyl-4,6
      dinitrotoluene, a product that is likely to be more amenable to subsequent
      biodegradation in the environment. Despite the presence of this biochemical
      detoxification pathway in plants, physiological concentrations of GST-U24 and GST
      U25 result in only a limited innate ability to cope with the levels of TNT found
      at contaminated sites. We demonstrate that Arabidopsis plants overexpressing GST
      U24 and GST-U25 exhibit significantly enhanced ability to withstand and detoxify
      TNT, properties that could be applied for in planta detoxification of TNT in the
      field. The overexpressing lines removed significantly more TNT from soil and
      exhibited a corresponding reduction in glutathione levels when compared with wild
      type plants. However, in the absence of TNT, overexpression of these GSTs reduces
      root and shoot biomass, and although glutathione levels are not affected, this
      effect has implications for xenobiotic detoxification.

PMID- 24733885
TI  - Endemism and functional convergence across the North American soil mycobiome.
AB  - Identifying the ecological processes that structure communities and the
      consequences for ecosystem function is a central goal of ecology. The recognition
      that fungi, bacteria, and viruses control key ecosystem functions has made
      microbial communities a major focus of this field. Because many ecological
      processes are apparent only at particular spatial or temporal scales, a complete
      understanding of the linkages between microbial community, environment, and
      function requires analysis across a wide range of scales. Here, we map the
      biological and functional geography of soil fungi from local to continental
      scales and show that the principal ecological processes controlling community
      structure and function operate at different scales. Similar to plants or animals,
      most soil fungi are endemic to particular bioregions, suggesting that factors
      operating at large spatial scales, like dispersal limitation or climate, are the
      first-order determinants of fungal community structure in nature. By contrast,
      soil extracellular enzyme activity is highly convergent across bioregions and
      widely differing fungal communities. Instead, soil enzyme activity is correlated
      with local soil environment and distribution of fungal traits within the
      community. The lack of structure-function relationships for soil fungal
      communities at continental scales indicates a high degree of functional
      redundancy among fungal communities in global biogeochemical cycles. 

PMID- 24733886
TI  - Optogenetic control of chemokine receptor signal and T-cell migration.
AB  - Adoptive cell transfer of ex vivo-generated immune-promoting or tolerogenic T
      cells to either enhance immunity or promote tolerance in patients has been used
      with some success. However, effective trafficking of the transferred cells to the
      target tissue sites is the main barrier to achieving successful clinical
      outcomes. Here we developed a strategy for optically controlling T-cell
      trafficking using a photoactivatable (PA) chemokine receptor. Photoactivatable
      chemokine C-X-C motif receptor 4 (PA-CXCR4) transmitted intracellular CXCR4
      signals in response to 505-nm light. Localized activation of PA-CXCR4 induced T
      cell polarization and directional migration (phototaxis) both in vitro and in
      vivo. Directing light onto the melanoma was sufficient to recruit PA-CXCR4
      expressing tumor-targeting cytotoxic T cells and improved the efficacy of
      adoptive T-cell transfer immunotherapy, with a significant reduction in tumor
      growth in mice. These findings suggest that the use of photoactivatable chemokine
      receptors allows remotely controlled leukocyte trafficking with outstanding
      spatial resolution in tissues and may be feasible in other cell transfer
      therapies. 

PMID- 24733887
TI  - X-ray structure of human aquaporin 2 and its implications for nephrogenic
      diabetes insipidus and trafficking.
AB  - Human aquaporin 2 (AQP2) is a water channel found in the kidney collecting duct,
      where it plays a key role in concentrating urine. Water reabsorption is regulated
      by AQP2 trafficking between intracellular storage vesicles and the apical
      membrane. This process is tightly controlled by the pituitary hormone arginine
      vasopressin and defective trafficking results in nephrogenic diabetes insipidus
      (NDI). Here we present the X-ray structure of human AQP2 at 2.75 A resolution.
      The C terminus of AQP2 displays multiple conformations with the C-terminal alpha
      helix of one protomer interacting with the cytoplasmic surface of a symmetry
      related AQP2 molecule, suggesting potential protein-protein interactions involved
      in cellular sorting of AQP2. Two Cd(2+)-ion binding sites are observed within the
      AQP2 tetramer, inducing a rearrangement of loop D, which facilitates this
      interaction. The locations of several NDI-causing mutations can be observed in
      the AQP2 structure, primarily situated within transmembrane domains and the
      majority of which cause misfolding and ER retention. These observations provide a
      framework for understanding why mutations in AQP2 cause NDI as well as structural
      insights into AQP2 interactions that may govern its trafficking. 

PMID- 24733888
TI  - Brf1 posttranscriptionally regulates pluripotency and differentiation responses
      downstream of Erk MAP kinase.
AB  - AU-rich element mRNA-binding proteins (AUBPs) are key regulators of development,
      but how they are controlled and what functional roles they play depends on
      cellular context. Here, we show that Brf1 (zfp36l1), an AUBP from the Zfp36
      protein family, operates downstream of FGF/Erk MAP kinase signaling to regulate
      pluripotency and cell fate decision making in mouse embryonic stem cells (mESCs).
      FGF/Erk MAP kinase signaling up-regulates Brf1, which disrupts the expression of
      core pluripotency-associated genes and attenuates mESC self-renewal without
      inducing differentiation. These regulatory effects are mediated by rapid and
      direct destabilization of Brf1 targets, such as Nanog mRNA. Enhancing Brf1
      expression does not compromise mESC pluripotency but does preferentially regulate
      mesendoderm commitment during differentiation, accelerating the expression of
      primitive streak markers. Together, these studies demonstrate that FGF signals
      use targeted mRNA degradation by Brf1 to enable rapid posttranscriptional control
      of gene expression in mESCs. 

PMID- 24733889
TI  - Initial steps of inactivation at the K+ channel selectivity filter.
AB  - K(+) efflux through K(+) channels can be controlled by C-type inactivation, which
      is thought to arise from a conformational change near the channel's selectivity
      filter. Inactivation is modulated by ion binding near the selectivity filter;
      however, the molecular forces that initiate inactivation remain unclear. We probe
      these driving forces by electrophysiology and molecular simulation of MthK, a
      prototypical K(+) channel. Either Mg(2+) or Ca(2+) can reduce K(+) efflux through
      MthK channels. However, Ca(2+), but not Mg(2+), can enhance entry to the
      inactivated state. Molecular simulations illustrate that, in the MthK pore,
      Ca(2+) ions can partially dehydrate, enabling selective accessibility of Ca(2+)
      to a site at the entry to the selectivity filter. Ca(2+) binding at the site
      interacts with K(+) ions in the selectivity filter, facilitating a conformational
      change within the filter and subsequent inactivation. These results support an
      ionic mechanism that precedes changes in channel conformation to initiate
      inactivation. 

PMID- 24733890
TI  - Transformation of the cerebellum into more ventral brainstem fates causes
      cerebellar agenesis in the absence of Ptf1a function.
AB  - Model organism studies have demonstrated that cell fate specification decisions
      play an important role in normal brain development. Their role in human
      neurodevelopmental disorders, however, is poorly understood, with very few
      examples described. The cerebellum is an excellent system to study mechanisms of
      cell fate specification. Although signals from the isthmic organizer are known to
      specify cerebellar territory along the anterior-posterior axis of the neural
      tube, the mechanisms establishing the cerebellar anlage along the dorsal-ventral
      axis are unknown. Here we show that the gene encoding pancreatic transcription
      factor PTF1A, which is inactivated in human patients with cerebellar agenesis, is
      required to segregate the cerebellum from more ventral extracerebellar fates.
      Using genetic fate mapping in mice, we show that in the absence of Ptf1a, cells
      originating in the cerebellar ventricular zone initiate a more ventral brainstem
      expression program, including LIM homeobox transcription factor 1 beta and T-cell
      leukemia homeobox 3. Misspecified cells exit the cerebellar anlage and contribute
      to the adjacent brainstem or die, leading to cerebellar agenesis in Ptf1a
      mutants. Our data identify Ptf1a as the first gene involved in the segregation of
      the cerebellum from the more ventral brainstem. Further, we propose that
      cerebellar agenesis represents a new, dorsal-to-ventral, cell fate
      misspecification phenotype in humans. 

PMID- 24733891
TI  - Conserved electron donor complex Dre2-Tah18 is required for ribonucleotide
      reductase metallocofactor assembly and DNA synthesis.
AB  - Eukaryotic ribonucleotide reductases (RNRs) require a diferric-tyrosyl radical
      (Fe(III)2-Y*) cofactor to produce deoxynucleotides essential for DNA replication
      and repair. This metallocofactor is an important target of RNR-based
      therapeutics, although mechanisms of in vivo cofactor assembly, inactivation, and
      reactivation are poorly understood. Here, we demonstrate that the conserved Fe-S
      protein-diflavin reductase complex, Dre2-Tah18, plays a critical role in RNR
      cofactor biosynthesis. Depletion of Dre2 affects both RNR gene transcription and
      mRNA turnover through the activation of the DNA-damage checkpoint and the
      Aft1/Aft2-controlled iron regulon. Under conditions of comparable RNR protein
      levels, cells with diminishing Dre2 have significantly reduced ability to make
      deoxynucleotides. Furthermore, the kinetics and levels of in vivo reconstitution
      of the RNR cofactor are severely impaired in two conditional tah18 mutants.
      Together, these findings provide insight into RNR cofactor formation and reveal a
      shared mechanism underlying assembly of the Fe(III)2-Y* cofactor in RNR and the
      Fe-S clusters in cytosolic and nuclear proteins. 

PMID- 24733892
TI  - Gq/5-HT2c receptor signals activate a local GABAergic inhibitory feedback circuit
      to modulate serotonergic firing and anxiety in mice.
AB  - Serotonin 2c receptors (5-HT2c-Rs) are drug targets for certain mental disorders,
      including schizophrenia, depression, and anxiety. 5-HT2c-Rs are expressed
      throughout the brain, making it difficult to link behavioral changes to circuit
      specific receptor expression. Various 5-HT-Rs, including 5-HT2c-Rs, are found in
      the dorsal raphe nucleus (DRN); however, the function of 5-HT2c-Rs and their
      influence on the serotonergic signals mediating mood disorders remain unclear. To
      investigate the role of 5-HT2c-Rs in the DRN in mice, we developed a melanopsin
      based optogenetic probe for activation of Gq signals in cellular domains, where 5
      HT2c-Rs are localized. Our results demonstrate that precise temporal control of
      Gq signals in 5-HT2c-R domains in GABAergic neurons upstream of 5-HT neurons
      provides negative feedback regulation of serotonergic firing to modulate anxiety
      like behavior in mice. 

PMID- 24733893
TI  - Structural basis for regulation of rhizobial nodulation and symbiosis gene
      expression by the regulatory protein NolR.
AB  - The symbiosis between rhizobial microbes and host plants involves the coordinated
      expression of multiple genes, which leads to nodule formation and nitrogen
      fixation. As part of the transcriptional machinery for nodulation and symbiosis
      across a range of Rhizobium, NolR serves as a global regulatory protein. Here, we
      present the X-ray crystal structures of NolR in the unliganded form and complexed
      with two different 22-base pair (bp) double-stranded operator sequences (oligos
      AT and AA). Structural and biochemical analysis of NolR reveals protein-DNA
      interactions with an asymmetric operator site and defines a mechanism for
      conformational switching of a key residue (Gln56) to accommodate variation in
      target DNA sequences from diverse rhizobial genes for nodulation and symbiosis.
      This conformational switching alters the energetic contributions to DNA binding
      without changes in affinity for the target sequence. Two possible models for the
      role of NolR in the regulation of different nodulation and symbiosis genes are
      proposed. To our knowledge, these studies provide the first structural insight on
      the regulation of genes involved in the agriculturally and ecologically important
      symbiosis of microbes and plants that leads to nodule formation and nitrogen
      fixation. 

PMID- 24733894
TI  - Hepatitis C virus triggers mitochondrial fission and attenuates apoptosis to
      promote viral persistence.
AB  - Mitochondrial dynamics is crucial for the regulation of cell homeostasis. Our
      recent findings suggest that hepatitis C virus (HCV) promotes Parkin-mediated
      elimination of damaged mitochondria (mitophagy). Here we show that HCV perturbs
      mitochondrial dynamics by promoting mitochondrial fission followed by mitophagy,
      which attenuates HCV-induced apoptosis. HCV infection stimulated expression of
      dynamin-related protein 1 (Drp1) and its mitochondrial receptor, mitochondrial
      fission factor. HCV further induced the phosphorylation of Drp1 (Ser616) and
      caused its subsequent translocation to the mitochondria, followed by mitophagy.
      Interference of HCV-induced mitochondrial fission and mitophagy by Drp1 silencing
      suppressed HCV secretion, with a concomitant decrease in cellular glycolysis and
      ATP levels, as well as enhanced innate immune signaling. More importantly,
      silencing Drp1 or Parkin caused significant increase in apoptotic signaling,
      evidenced by increased cytochrome C release from mitochondria, caspase 3
      activity, and cleavage of poly(ADP-ribose) polymerase. These results suggest that
      HCV-induced mitochondrial fission and mitophagy serve to attenuate apoptosis and
      may contribute to persistent HCV infection. 

PMID- 24733895
TI  - PDGFRbeta reverses EphB4 signaling in alveolar rhabdomyosarcoma.
AB  - Alveolar rhabdomyosarcoma (aRMS) is an aggressive myogenic childhood malignancy,
      not infrequently presenting as incurable metastatic disease. To identify
      therapeutic targets, we performed an unbiased tyrosine kinome RNA interference
      screen in primary cell cultures from a genetically engineered, conditional mouse
      model of aRMS. We identified ephrin receptor B4 (EphB4) as a target that is
      widely expressed in human aRMS and that portends a poor clinical outcome in an
      expression level-dependent manner. We also uncovered cross-talk of this ephrin
      receptor with another receptor tyrosine kinase, PDGFRbeta, which facilitates PDGF
      ligand-dependent, ephrin ligand-independent activation of EphB4 converging on the
      Akt and Erk1/2 pathways. Conversely, EphB4 activation by its cognate ligand,
      EphrinB2, did not stimulate PDGFRbeta; instead, apoptosis was paradoxically
      induced. Finally, we showed that small-molecule inhibition of both PDGFRbeta and
      EphB4 by dasatinib resulted in a significant decrease in tumor cell viability in
      vitro, as well as decreased tumor growth rate and significantly prolonged
      survival in vivo. To our knowledge, these results are the first to identify EphB4
      and its cross-talk with PDGFRbeta as unexpected vital determinants of tumor cell
      survival in aRMS, with EphB4 at the crux of a bivalent signaling node that is
      either mitogenic or proapoptotic. 

PMID- 24733896
TI  - Evolutionary pathway to increased virulence and epidemic group A Streptococcus
      disease derived from 3,615 genome sequences.
AB  - We sequenced the genomes of 3,615 strains of serotype Emm protein 1 (M1) group A
      Streptococcus to unravel the nature and timing of molecular events contributing
      to the emergence, dissemination, and genetic diversification of an unusually
      virulent clone that now causes epidemic human infections worldwide. We discovered
      that the contemporary epidemic clone emerged in stepwise fashion from a precursor
      cell that first contained the phage encoding an extracellular DNase virulence
      factor (streptococcal DNase D2, SdaD2) and subsequently acquired the phage
      encoding the SpeA1 variant of the streptococcal pyrogenic exotoxin A
      superantigen. The SpeA2 toxin variant evolved from SpeA1 by a single-nucleotide
      change in the M1 progenitor strain before acquisition by horizontal gene transfer
      of a large chromosomal region encoding secreted toxins NAD(+)-glycohydrolase and
      streptolysin O. Acquisition of this 36-kb region in the early 1980s into just one
      cell containing the phage-encoded sdaD2 and speA2 genes was the final major
      molecular event preceding the emergence and rapid intercontinental spread of the
      contemporary epidemic clone. Thus, we resolve a decades-old controversy about the
      type and sequence of genomic alterations that produced this explosive epidemic.
      Analysis of comprehensive, population-based contemporary invasive strains from
      seven countries identified strong patterns of temporal population structure.
      Compared with a preepidemic reference strain, the contemporary clone is
      significantly more virulent in nonhuman primate models of pharyngitis and
      necrotizing fasciitis. A key finding is that the molecular evolutionary events
      transpiring in just one bacterial cell ultimately have produced millions of human
      infections worldwide. 

PMID- 24733897
TI  - Transcription factors TFIIF and TFIIS promote transcript elongation by RNA
      polymerase II by synergistic and independent mechanisms.
AB  - Recent evidence suggests that transcript elongation by RNA polymerase II (RNAPII)
      is regulated by mechanical cues affecting the entry into, and exit from,
      transcriptionally inactive states, including pausing and arrest. We present a
      single-molecule optical-trapping study of the interactions of RNAPII with
      transcription elongation factors TFIIS and TFIIF, which affect these processes.
      By monitoring the response of elongation complexes containing RNAPII and
      combinations of TFIIF and TFIIS to controlled mechanical loads, we find that both
      transcription factors are independently capable of restoring arrested RNAPII to
      productive elongation. TFIIS, in addition to its established role in promoting
      transcript cleavage, is found to relieve arrest by a second, cleavage-independent
      mechanism. TFIIF synergistically enhances some, but not all, of the activities of
      TFIIS. These studies also uncovered unexpected insights into the mechanisms
      underlying transient pauses. The direct visualization of pauses at near-base-pair
      resolution, together with the load dependence of the pause-entry phase, suggests
      that two distinct mechanisms may be at play: backtracking under forces that
      hinder transcription and a backtrack-independent activity under assisting loads.
      The measured pause lifetime distributions are inconsistent with prevailing views
      of backtracking as a purely diffusive process, suggesting instead that the extent
      of backtracking may be modulated by mechanisms intrinsic to RNAPII. Pauses
      triggered by inosine triphosphate misincorporation led to backtracking, even
      under assisting loads, and their lifetimes were reduced by TFIIS, particularly
      when aided by TFIIF. Overall, these experiments provide additional insights into
      how obstacles to transcription may be overcome by the concerted actions of
      multiple accessory factors. 

PMID- 24733898
TI  - Horizontal transfer of an adaptive chimeric photoreceptor from bryophytes to
      ferns.
AB  - Ferns are well known for their shade-dwelling habits. Their ability to thrive
      under low-light conditions has been linked to the evolution of a novel chimeric
      photoreceptor--neochrome--that fuses red-sensing phytochrome and blue-sensing
      phototropin modules into a single gene, thereby optimizing phototropic responses.
      Despite being implicated in facilitating the diversification of modern ferns, the
      origin of neochrome has remained a mystery. We present evidence for neochrome in
      hornworts (a bryophyte lineage) and demonstrate that ferns acquired neochrome
      from hornworts via horizontal gene transfer (HGT). Fern neochromes are nested
      within hornwort neochromes in our large-scale phylogenetic reconstructions of
      phototropin and phytochrome gene families. Divergence date estimates further
      support the HGT hypothesis, with fern and hornwort neochromes diverging 179 Mya,
      long after the split between the two plant lineages (at least 400 Mya). By
      analyzing the draft genome of the hornwort Anthoceros punctatus, we also
      discovered a previously unidentified phototropin gene that likely represents the
      ancestral lineage of the neochrome phototropin module. Thus, a neochrome
      originating in hornworts was transferred horizontally to ferns, where it may have
      played a significant role in the diversification of modern ferns.

PMID- 24733899
TI  - Thalamocortical rhythms during a vibrotactile detection task.
AB  - To explore the role of oscillatory dynamics of the somatosensory thalamocortical
      network in perception and decision making, we recorded the simultaneous neuronal
      activity in the ventral posterolateral nucleus (VPL) of the somatosensory
      thalamus and primary somatosensory cortex (S1) in two macaque monkeys performing
      a vibrotactile detection task. Actively detecting a vibrotactile stimulus and
      reporting its perception elicited a sustained poststimulus beta power increase in
      VPL and an alpha power decrease in S1, in both stimulus-present and stimulus
      absent trials. These oscillatory dynamics in the somatosensory thalamocortical
      network depended on the behavioral context: they were stronger for the active
      detection condition than for a passive stimulation condition. Furthermore,
      contrasting stimulus-present vs. stimulus-absent responses, we found that
      poststimulus theta power increased in both VPL and S1, and alpha/beta power
      decreased in S1, reflecting the monkey's perceptual decision but not the motor
      response per se. Additionally, higher prestimulus alpha power in S1 correlated
      with an increased probability of the monkey reporting a stimulus, regardless of
      the actual presence of a stimulus. Thus, we found task-related modulations in
      oscillatory activity, not only in the neocortex but also in the thalamus,
      depending on behavioral context. Furthermore, oscillatory modulations reflected
      the perceptual decision process and subsequent behavioral response. We conclude
      that these early sensory regions, in addition to their primary sensory functions,
      may be actively involved in perceptual decision making. 

PMID- 24733900
TI  - Selective inhibition of the function of tyrosine-phosphorylated STAT3 with a
      phosphorylation site-specific intrabody.
AB  - Signal transducer and activator of transcription 3 (STAT3) is a multifunctional
      protein that participates in signaling pathways initiated by various growth
      factors and cytokines. It exists in multiple forms including those phosphorylated
      on Tyr(705) (pYSTAT3) or Ser(727) (pSSTAT3) as well as the unphosphorylated
      protein (USTAT3). In addition to the canonical transcriptional regulatory role of
      pYSTAT3, both USTAT3 and pSSTAT3 function as transcriptional regulators by
      binding to distinct promoter sites and play signaling roles in the cytosol or
      mitochondria. The roles of each STAT3 species in different biological processes
      have not been readily amenable to investigation, however. We have now prepared an
      intrabody that binds specifically and with high affinity to the tyrosine
      phosphorylated site of pYSTAT3. Adenovirus-mediated expression of the intrabody
      in HepG2 cells as well as mouse liver blocked both the accumulation of pYSTAT3 in
      the nucleus and the production of acute phase response proteins induced by
      interleukin-6. Intrabody expression did not affect the overall accumulation of
      pSSTAT3 induced by interleukin-6 or phorbol 12-myristate 13-acetate (PMA), the
      PMA-induced expression of the c-Fos gene, or the PMA-induced accumulation of
      pSSTAT3 specifically in mitochondria. In addition, it had no effect on
      interleukin-6-induced expression of the gene for IFN regulatory factor 1, a
      downstream target of STAT1. Our results suggest that the engineered intrabody is
      able to block specifically the downstream effects of pYSTAT3 without influencing
      those of pSSTAT3, demonstrating the potential of intrabodies as tools to dissect
      the cellular functions of specific modified forms of proteins that exist as
      multiple species. 

PMID- 24733902
TI  - Closing the gap between viral and noninfectious arthritis.

PMID- 24733901
TI  - MicroRNAs are critical regulators of tuberous sclerosis complex and mTORC1
      activity in the size control of the Xenopus kidney.
AB  - MicroRNAs (miRNAs) are major posttranscriptional regulators of a wide variety of
      biological processes. However, redundancy among most miRNAs has made it difficult
      to identify their in vivo functions. We previously demonstrated that global
      inhibition of miRNA biogenesis in Xenopus resulted in a dramatically smaller
      pronephric kidney. This suggested that microRNAs play a pivotal role in organ
      size control. Here we now provide a detailed mechanistic explanation for this
      phenotype. We identified that the activation of the mechanistic target of
      rapamycin complex 1 (mTORC1) by Insulin and insulin-like growth factor (Igf) 2 is
      an important regulator in kidney growth, which in turn is modulated by microRNAs.
      Molecular analyses demonstrate that microRNAs set a threshold for mTORC1
      signaling by down-regulating one of its core negative regulators, tuberous
      sclerosis 1 (Tsc1). Most importantly, this rheostat can be reprogrammed
      experimentally. Whereas knockdown of miRNAs causes growth arrest, concomitant
      knockdown of Tsc1 restores mTORC1 activity and proximal tubular size. Together,
      these data establish a previously unidentified in vivo paradigm for the
      importance of posttranscriptional regulation in organ size control. 

PMID- 24733903
TI  - Rapidly reversible redox transformation in nanophase manganese oxides at room
      temperature triggered by changes in hydration.
AB  - Chemisorption of water onto anhydrous nanophase manganese oxide surfaces promotes
      rapidly reversible redox phase changes as confirmed by calorimetry, X-ray
      diffraction, and titration for manganese average oxidation state. Surface
      reduction of bixbyite (Mn2O3) to hausmannite (Mn3O4) occurs in nanoparticles
      under conditions where no such reactions are seen or expected on grounds of bulk
      thermodynamics in coarse-grained materials. Additionally, transformation does not
      occur on nanosurfaces passivated by at least 2% coverage of what is likely an
      amorphous manganese oxide layer. The transformation is due to thermodynamic
      control arising from differences in surface energies of the two phases (Mn2O3 and
      Mn3O4) under wet and dry conditions. Such reversible and rapid transformation
      near room temperature may affect the behavior of manganese oxides in
      technological applications and in geologic and environmental settings. 

PMID- 24733904
TI  - Essential role for TrpC5-containing extracellular vesicles in breast cancer with
      chemotherapeutic resistance.
AB  - A critical challenge for chemotherapy is the development of chemoresistance in
      breast cancer. However, the underlying mechanisms and validated predictors remain
      unclear. Extracellular vesicles (EVs) have gained attention as potential means
      for cancer cells to share intracellular contents. In adriamycin-resistant human
      breast cancer cells (MCF-7/ADM), we analyzed the role of transient receptor
      potential channel 5 (TrpC5) in EV formation and transfer as well as the
      diagnostic implications. Up-regulated TrpC5, accumulated in EVs, is responsible
      for EV formation and trapping of adriamycin (ADM) in EVs. EV-mediated
      intercellular transfer of TrpC5 allowed recipient cells to acquire TrpC5,
      consequently stimulating multidrug efflux transporter P-glycoprotein production
      through a Ca(2+)- and activated T-cells isoform c3-mediated mechanism and thus,
      conferring chemoresistance on nonresistant cells. TrpC5-containing circulating
      EVs were detected in nude mice bearing MCF-7/ADM tumor xenografts, and the level
      was lower after TrpC5-siRNA treatment. In breast cancer patients who underwent
      chemotherapy, TrpC5 expression in the tumor was significantly higher in patients
      with progressive or stable disease than in patients with a partial or complete
      response. TrpC5-containing circulating EVs were found in peripheral blood from
      patients who underwent chemotherapy but not patients without chemotherapy. Taken
      together, we found that TrpC5-containing circulating EVs may transfer
      chemoresistance property to nonchemoresistant recipient cells. It may be
      worthwhile to further explore the potential of using TrpC5-containing EVs as a
      diagnostic biomarker for chemoresistant breast cancer. 

PMID- 24733905
TI  - Rescuing US biomedical research from its systemic flaws.
AB  - The long-held but erroneous assumption of never-ending rapid growth in biomedical
      science has created an unsustainable hypercompetitive system that is discouraging
      even the most outstanding prospective students from entering our profession--and
      making it difficult for seasoned investigators to produce their best work. This
      is a recipe for long-term decline, and the problems cannot be solved with
      simplistic approaches. Instead, it is time to confront the dangers at hand and
      rethink some fundamental features of the US biomedical research ecosystem.

PMID- 24733906
TI  - Strong interlayer coupling in van der Waals heterostructures built from single
      layer chalcogenides.
AB  - Semiconductor heterostructures are the fundamental platform for many important
      device applications such as lasers, light-emitting diodes, solar cells, and high
      electron-mobility transistors. Analogous to traditional heterostructures, layered
      transition metal dichalcogenide heterostructures can be designed and built by
      assembling individual single layers into functional multilayer structures, but in
      principle with atomically sharp interfaces, no interdiffusion of atoms, digitally
      controlled layered components, and no lattice parameter constraints. Nonetheless,
      the optoelectronic behavior of this new type of van der Waals (vdW) semiconductor
      heterostructure is unknown at the single-layer limit. Specifically, it is
      experimentally unknown whether the optical transitions will be spatially direct
      or indirect in such hetero-bilayers. Here, we investigate artificial
      semiconductor heterostructures built from single-layer WSe2 and MoS2. We observe
      a large Stokes-like shift of ~ 100 meV between the photoluminescence peak and the
      lowest absorption peak that is consistent with a type II band alignment having
      spatially direct absorption but spatially indirect emission. Notably, the
      photoluminescence intensity of this spatially indirect transition is strong,
      suggesting strong interlayer coupling of charge carriers. This coupling at the
      hetero-interface can be readily tuned by inserting dielectric layers into the vdW
      gap, consisting of hexagonal BN. Consequently, the generic nature of this
      interlayer coupling provides a new degree of freedom in band engineering and is
      expected to yield a new family of semiconductor heterostructures having tunable
      optoelectronic properties with customized composite layers.

PMID- 24733907
TI  - Discovery of LPMO activity on hemicelluloses shows the importance of oxidative
      processes in plant cell wall degradation.
AB  - The recently discovered lytic polysaccharide monooxygenases (LPMOs) are known to
      carry out oxidative cleavage of glycoside bonds in chitin and cellulose, thus
      boosting the activity of well-known hydrolytic depolymerizing enzymes. Because
      biomass-degrading microorganisms tend to produce a plethora of LPMOs, and
      considering the complexity and copolymeric nature of the plant cell wall, it has
      been speculated that some LPMOs may act on other substrates, in particular the
      hemicelluloses that tether to cellulose microfibrils. We demonstrate that an LPMO
      from Neurospora crassa, NcLPMO9C, indeed degrades various hemicelluloses, in
      particular xyloglucan. This activity was discovered using a glycan microarray
      based screening method for detection of substrate specificities of carbohydrate
      active enzymes, and further explored using defined oligomeric hemicelluloses,
      isolated polymeric hemicelluloses and cell walls. Products generated by NcLPMO9C
      were analyzed using high performance anion exchange chromatography and
      multidimensional mass spectrometry. We show that NcLPMO9C generates oxidized
      products from a variety of substrates and that its product profile differs from
      those of hydrolytic enzymes acting on the same substrates. The enzyme
      particularly acts on the glucose backbone of xyloglucan, accepting various
      substitutions (xylose, galactose) in almost all positions. Because the attachment
      of xyloglucan to cellulose hampers depolymerization of the latter, it is possible
      that the beneficial effect of the LPMOs that are present in current commercial
      cellulase mixtures in part is due to hitherto undetected LPMO activities on
      recalcitrant hemicellulose structures. 

PMID- 24733908
TI  - Sea star tenacity mediated by a protein that fragments, then aggregates.
AB  - Sea stars adhere firmly but temporarily to various substrata as a result of
      underwater efficient adhesive secretions released by their tube feet. Previous
      studies showed that this material is mainly made up of proteins, which play a key
      role in its adhesiveness and cohesiveness. Recently, we solubilized the majority
      of these proteins and obtained 43 de novo-generated peptide sequences by tandem
      MS. Here, one of these sequences served to recover the full-length sequence of
      Sea star footprint protein 1 (Sfp1), by RT-PCR and tube foot transcriptome
      analysis. Sfp1, a large protein of 3,853 aa, is the second most abundant
      constituent of the secreted adhesive. By using MS and Western blot analyses, we
      showed that Sfp1 is translated from a single mRNA and then cleaved into four
      subunits linked together by disulphide bridges in tube foot adhesive cells. The
      four subunits display specific protein-, carbohydrate-, and metal-binding
      domains. Immunohistochemistry and immunocytochemistry located Sfp1 in granules
      stockpiled by one of the two types of adhesive cells responsible for the
      secretion of the adhesive material. We also demonstrated that Sfp1 makes up the
      structural scaffold of the adhesive footprint that remains on the substratum
      after tube foot detachment. Taken together, the results suggest that Sfp1 is a
      major structural protein involved in footprint cohesion and possibly in adhesive
      interactions with the tube foot surface. In recombinant form, it could be used
      for the design of novel sea star-inspired biomaterials. 

PMID- 24733909
TI  - Younger Dryas deglaciation of Scotland driven by warming summers.
AB  - The Younger Dryas Stadial (YDS; ~ 12,900-11,600 y ago) in the Northern Hemisphere
      is classically defined by abrupt cooling and renewed glaciation during the last
      glacial-interglacial transition. Although this event involved a global
      reorganization of atmospheric and oceanic circulation [Denton GH, Alley RB, Comer
      GC, Broecker WS (2005) Quat Sci Rev 24:1159-1182], the magnitude, seasonality,
      and geographical footprint of YDS cooling remain unresolved and pose a challenge
      to our understanding of abrupt climate change. Here, we present a deglacial
      chronology from Scotland, immediately downwind of the North Atlantic Ocean,
      indicating that the Scottish ice cap disintegrated during the first half of the
      YDS. We suggest that stratification of the North Atlantic Ocean resulted in
      amplified seasonality that, paradoxically, stimulated a severe wintertime climate
      while promoting warming summers through solar heating of the mixed layer. This
      latter process drove deglaciation of downwind landmasses to completion well
      before the end of the YDS.

PMID- 24733910
TI  - Humoral response to a viral glycan correlates with survival on PROSTVAC-VF.
AB  - Therapeutic cancer vaccines can be effective for treating patients, but clinical
      responses vary considerably from patient to patient. Early indicators of a
      favorable response are crucial for making individualized treatment decisions and
      advancing vaccine design, but no validated biomarkers are currently available. In
      this study, we used glycan microarrays to profile antiglycan antibody responses
      induced by PROSTVAC-VF, a poxvirus-based cancer vaccine currently in phase III
      clinical trials. Although the vaccine is designed to induce T-cell responses to
      prostate-specific antigen, we demonstrate that this vaccine also induces humoral
      responses to a carbohydrate on the poxvirus, the Forssman disaccharide
      (GalNAcalpha1-3GalNAcbeta). These responses had a statistically significant
      correlation with overall survival in two independent sample sets (P = 0.015 and
      0.008) comprising more than 100 patients. Additionally, anti-Forssman humoral
      responses correlated with clinical outcome in a separate study of PROSTVAC-VF
      combined with a radiopharmaceutical (Quadramet). Studies on control subjects
      demonstrated that the survival correlation was specific to the vaccine. The
      results provide evidence that antiglycan antibody responses may serve as early
      biomarkers of a favorable response to PROSTVAC-VF and offer unique insights for
      improving vaccine design. 

PMID- 24733911
TI  - Methylation protects microRNAs from an AGO1-associated activity that uridylates
      5' RNA fragments generated by AGO1 cleavage.
AB  - In plants, methylation catalyzed by HEN1 (small RNA methyl transferase) prevents
      microRNAs (miRNAs) from degradation triggered by uridylation. How methylation
      antagonizes uridylation of miRNAs in vivo is not well understood. In addition, 5'
      RNA fragments (5' fragments) produced by miRNA-mediated RNA cleavage can be
      uridylated in plants and animals. However, the biological significance of this
      modification is unknown, and enzymes uridylating 5' fragments remain to be
      identified. Here, we report that in Arabidopsis, HEN1 suppressor 1 (HESO1, a
      miRNA nucleotidyl transferase) uridylates 5' fragments to trigger their
      degradation. We also show that Argonaute 1 (AGO1), the effector protein of
      miRNAs, interacts with HESO1 through its Piwi/Argonaute/Zwille and PIWI domains,
      which bind the 3' end of miRNA and cleave the target mRNAs, respectively.
      Furthermore, HESO1 is able to uridylate AGO1-bound miRNAs in vitro. miRNA
      uridylation in vivo requires a functional AGO1 in hen1, in which miRNA
      methylation is impaired, demonstrating that HESO1 can recognize its substrates in
      the AGO1 complex. On the basis of these results, we propose that methylation is
      required to protect miRNAs from AGO1-associated HESO1 activity that normally
      uridylates 5' fragments. 

PMID- 24733912
TI  - Enhanced evolution by stochastically variable modification of epigenetic marks in
      the early embryo.
AB  - Evolution by gene duplication is generally accepted as one of the crucial driving
      forces for the gain of new complexity and functions, but the formation of
      pseudogenes remains a problem for this mechanism. Here we expand on earlier ideas
      that epigenetic modifications can drive neo- and subfunctionalization in
      evolution by gene duplication. We explore the effects of stochastic epigenetic
      modifications on the evolution (and thus development) of complex organisms in a
      constant environment. Modeling is done both using a modified genetic drift
      analytical treatment and computer simulations, which were found to agree. A
      transposon silencing model is also explored. Some key assumptions made include
      (i) stochastic, incomplete removal (or addition) of repressive epigenetic marks
      takes place during a window(s) of opportunity in the zygote and early embryo;
      (ii) there is no statistical variation of the marks after the window closes; and
      (iii) the genes affected are sensitive to dosage. Our genetic drift treatment
      takes into account that after gene duplication the prevailing case upon which
      selection operates is a duplicate/singlet heterozygote; to the best of our
      knowledge, this has not been considered in previous treatments. We conclude from
      our modeling that stochastic epigenetic modifications, with rates consistent with
      experimental observation, can both increase the rate of gene fixation and
      decrease pseudogenization, thus dramatically improving the efficacy of evolution
      by gene duplication. We also find that a transposon silencing model is
      advantageous for fixation of recessive genes in diploid organisms, especially
      with large effective population sizes. 

PMID- 24733913
TI  - Regional cerebral metabolic patterns demonstrate the role of anterior forebrain
      mesocircuit dysfunction in the severely injured brain.
AB  - Although disorders of consciousness (DOCs) demonstrate widely varying clinical
      presentations and patterns of structural injury, global down-regulation and
      bilateral reductions in metabolism of the thalamus and frontoparietal network are
      consistent findings. We test the hypothesis that global reductions of background
      synaptic activity in DOCs will associate with changes in the pattern of metabolic
      activity in the central thalamus and globus pallidus. We compared 32
      [(18)F]fluorodeoxyglucose PETs obtained from severely brain-injured patients
      (BIs) and 10 normal volunteers (NVs). We defined components of the anterior
      forebrain mesocircuit on high-resolution T1-MRI (ventral, associative, and
      sensorimotor striatum; globus pallidus; central thalamus and noncentral
      thalamus). Metabolic profiles for BI and NV demonstrated distinct changes in the
      pattern of uptake: ventral and association striatum (but not sensorimotor) were
      significantly reduced relative to global mean uptake after BI; a relative
      increase in globus pallidus metabolism was evident in BI subjects who also showed
      a relative reduction of metabolism in the central thalamus. The reversal of
      globus pallidus and central thalamus profiles across BIs and NVs supports the
      mesocircuit hypothesis that broad functional (or anatomic) deafferentation may
      combine to reduce central thalamus activity and release globus pallidus activity
      in DOCs. In addition, BI subjects showed broad frontoparietal metabolic down
      regulation consistent with prior studies supporting the link between central
      thalamic/pallidal metabolism and down-regulation of the frontoparietal network.
      Recovery of left hemisphere frontoparietal metabolic activity was further
      associated with command following. 

PMID- 24733914
TI  - Arthritogenic alphaviral infection perturbs osteoblast function and triggers
      pathologic bone loss.
AB  - Arthritogenic alphaviruses including Ross River virus (RRV), Sindbis virus, and
      chikungunya virus cause worldwide outbreaks of musculoskeletal disease. The
      ability of alphaviruses to induce bone pathologies remains poorly defined. Here
      we show that primary human osteoblasts (hOBs) can be productively infected by
      RRV. RRV-infected hOBs produced high levels of inflammatory cytokine including IL
      6. The RANKL/OPG ratio was disrupted in the synovial fluid of RRV patients, and
      this was accompanied by an increase in serum Tartrate-resistant acid phosphatase
      5b (TRAP5b) levels. Infection of bone cells with RRV was validated using an
      established RRV murine model. In wild-type mice, infectious virus was detected in
      the femur, tibia, patella, and foot, together with reduced bone volume in the
      tibial epiphysis and vertebrae detected by microcomputed tomographic (uCT)
      analysis. The RANKL/OPG ratio was also disrupted in mice infected with RRV; both
      this effect and the bone loss were blocked by treatment with an IL-6 neutralizing
      antibody. Collectively, these findings provide previously unidentified evidence
      that alphavirus infection induces bone loss and that OBs are capable of producing
      proinflammatory mediators during alphavirus-induced arthralgia. The perturbed
      RANKL/OPG ratio in RRV-infected OBs may therefore contribute to bone loss in
      alphavirus infection. 

PMID- 24733915
TI  - Tau mutants bind tubulin heterodimers with enhanced affinity.
AB  - Tau is a microtubule binding protein that forms pathological aggregates in the
      brain in Alzheimer's disease and other tauopathies. Disease etiology is thought
      to arise from loss of native interactions between tau and microtubules, as well
      as from gain of toxicity tied to tau aggregation, although neither mechanism is
      well understood. Here we investigate the link between function and disease using
      disease-associated and disease-motivated mutants of tau. We find that mutations
      to highly conserved proline residues in repeats 2 and 3 of the microtubule
      binding domain have differential effects on tau binding to tubulin and the
      capacity of tau to enhance tubulin polymerization. Notably, mutations to these
      residues result in an increased affinity for tubulin dimers while having a
      negligible effect on binding to stabilized microtubules. We measure
      conformational changes in tau on binding to tubulin that provide a structural
      framework for the observed altered affinity and function. Additionally, we find
      that these mutations do not necessarily enhance aggregation, which could have
      important implications for tau therapeutic strategies that focus solely on
      searching for tau aggregation inhibitors. We propose a model that describes tau
      binding to tubulin dimers and a mechanism by which disease-relevant alterations
      to tau impact its function. Together, these results draw attention to the
      interaction between tau and free tubulin as playing an important role in
      mechanisms of tau pathology. 

PMID- 24733916
TI  - Tetherin antagonism by Vpu protects HIV-infected cells from antibody-dependent
      cell-mediated cytotoxicity.
AB  - Tetherin is an IFN-inducible transmembrane protein that inhibits the detachment
      of enveloped viruses from infected cells. HIV-1 overcomes this restriction factor
      by expressing HIV-1 viral protein U (Vpu), which down-regulates and degrades
      tetherin. We report that mutations in Vpu that impair tetherin antagonism
      increase the susceptibility of HIV-infected cells to antibody-dependent cell
      mediated cytotoxicity (ADCC), and conversely that RNAi knockdown of tetherin, but
      not other cellular proteins down-modulated by Vpu, decreases the susceptibility
      of HIV-infected cells to ADCC. These results reveal that Vpu protects HIV
      infected cells from ADCC as a function of its ability to counteract tetherin. By
      serving as link between innate and adaptive immunity, the antiviral activity of
      tetherin may be augmented by virus-specific antibodies, and hence much greater
      than previously appreciated. 

PMID- 24733917
TI  - Incomplete Wood-Ljungdahl pathway facilitates one-carbon metabolism in
      organohalide-respiring Dehalococcoides mccartyi.
AB  - The acetyl-CoA "Wood-Ljungdahl" pathway couples the folate-mediated one-carbon
      (C1) metabolism to either CO2 reduction or acetate oxidation via acetyl-CoA. This
      pathway is distributed in diverse anaerobes and is used for both energy
      conservation and assimilation of C1 compounds. Genome annotations for all
      sequenced strains of Dehalococcoides mccartyi, an important bacterium involved in
      the bioremediation of chlorinated solvents, reveal homologous genes encoding an
      incomplete Wood-Ljungdahl pathway. Because this pathway lacks key enzymes for
      both C1 metabolism and CO2 reduction, its cellular functions remain elusive. Here
      we used D. mccartyi strain 195 as a model organism to investigate the metabolic
      function of this pathway and its impacts on the growth of strain 195.
      Surprisingly, this pathway cleaves acetyl-CoA to donate a methyl group for
      production of methyl-tetrahydrofolate (CH3-THF) for methionine biosynthesis,
      representing an unconventional strategy for generating CH3-THF in organisms
      without methylene-tetrahydrofolate reductase. Carbon monoxide (CO) was found to
      accumulate as an obligate by-product from the acetyl-CoA cleavage because of the
      lack of a CO dehydrogenase in strain 195. CO accumulation inhibits the
      sustainable growth and dechlorination of strain 195 maintained in pure cultures,
      but can be prevented by CO-metabolizing anaerobes that coexist with D. mccartyi,
      resulting in an unusual syntrophic association. We also found that this pathway
      incorporates exogenous formate to support serine biosynthesis. This study of the
      incomplete Wood-Ljungdahl pathway in D. mccartyi indicates a unique bacterial C1
      metabolism that is critical for D. mccartyi growth and interactions in
      dechlorinating communities and may play a role in other anaerobic communities. 

PMID- 24733918
TI  - Measurement of histidine pKa values and tautomer populations in invisible protein
      states.
AB  - The histidine imidazole side chain plays a critical role in protein function and
      stability. Its importance for catalysis is underscored by the fact that
      histidines are localized to active sites in ~ 50% of all enzymes. NMR
      spectroscopy has become an important tool for studies of histidine side chains
      through the measurement of site-specific pK(a)s and tautomer populations. To
      date, such studies have been confined to observable protein ground states;
      however, a complete understanding of the role of histidine electrostatics in
      protein function and stability requires that similar investigations be extended
      to rare, transiently formed conformers that populate the energy landscape, yet
      are often "invisible" in standard NMR spectra. Here we present NMR experiments
      and a simple strategy for studies of such conformationally excited states based
      on measurement of histidine (13)Cgamma, (13)Cdelta2 chemical shifts and
      (1)Hepsilon-(13)Cepsilon one-bond scalar couplings. The methodology is first
      validated and then used to obtain pKa values and tautomer distributions for
      histidine residues of an invisible on-pathway folding intermediate of the colicin
      E7 immunity protein. Our results imply that the side chains of H40 and H47 are
      exposed in the intermediate state and undergo significant conformational
      rearrangements during folding to the native structure. Further, the pKa values
      explain the pH-dependent stability differences between native and intermediate
      states over the pH range 5.5-6.5 and they suggest that imidazole deprotonation is
      not a barrier to the folding of this protein.

PMID- 24733920
TI  - Fundamental differences between Arctic and Antarctic ozone depletion.
AB  - Antarctic ozone depletion is associated with enhanced chlorine from anthropogenic
      chlorofluorocarbons and heterogeneous chemistry under cold conditions. The deep
      Antarctic "hole" contrasts with the generally weaker depletions observed in the
      warmer Arctic. An unusually cold Arctic stratospheric season occurred in 2011,
      raising the question of how the Arctic ozone chemistry in that year compares with
      others. We show that the averaged depletions near 20 km across the cold part of
      each pole are deeper in Antarctica than in the Arctic for all years, although
      2011 Arctic values do rival those seen in less-depleted years in Antarctica. We
      focus not only on averages but also on extremes, to address whether or not Arctic
      ozone depletion can be as extreme as that observed in the Antarctic. This
      information provides unique insights into the contrasts between Arctic and
      Antarctic ozone chemistry. We show that extreme Antarctic ozone minima fall to or
      below 0.1 parts per million by volume (ppmv) at 18 and 20 km (about 70 and 50
      mbar) whereas the lowest Arctic ozone values are about 0.5 ppmv at these
      altitudes. At a higher altitude of 24 km (30-mbar level), no Arctic data below
      about 2 ppmv have been observed, including in 2011, in contrast to values more
      than an order of magnitude lower in Antarctica. The data show that the lowest
      ozone values are associated with temperatures below -80  degrees C to -85 
      degrees C depending upon altitude, and are closely associated with reduced
      gaseous nitric acid concentrations due to uptake and/or sedimentation in polar
      stratospheric cloud particles. 

PMID- 24733919
TI  - Control of vacuolar dynamics and regulation of stomatal aperture by tonoplast
      potassium uptake.
AB  - Stomatal movements rely on alterations in guard cell turgor. This requires
      massive K(+) bidirectional fluxes across the plasma and tonoplast membranes.
      Surprisingly, given their physiological importance, the transporters mediating
      the energetically uphill transport of K(+) into the vacuole remain to be
      identified. Here, we report that, in Arabidopsis guard cells, the tonoplast
      localized K(+)/H(+) exchangers NHX1 and NHX2 are pivotal in the vacuolar
      accumulation of K(+) and that nhx1 nhx2 mutant lines are dysfunctional in
      stomatal regulation. Hypomorphic and complete-loss-of-function double mutants
      exhibited significantly impaired stomatal opening and closure responses.
      Disruption of K(+) accumulation in guard cells correlated with more acidic
      vacuoles and the disappearance of the highly dynamic remodelling of vacuolar
      structure associated with stomatal movements. Our results show that guard cell
      vacuolar accumulation of K(+) is a requirement for stomatal opening and a
      critical component in the overall K(+) homeostasis essential for stomatal
      closure, and suggest that vacuolar K(+) fluxes are also of decisive importance in
      the regulation of vacuolar dynamics and luminal pH that underlie stomatal
      movements. 

PMID- 24733921
TI  - Single bacterial strain capable of significant contribution to carbon cycling in
      the surface ocean.
AB  - Marine dissolved organic carbon (DOC) encompasses one of the largest reservoirs
      of carbon on Earth. Heterotrophic bacteria are the primary biotic force
      regulating the fate of this material, yet the capacity of individual strains to
      significantly contribute to carbon cycling is unknown. Here we quantified the
      ability of a single Alteromonas strain [Alteromonas sp. strain Scripps
      Institution of Oceanography (AltSIO)] to drawdown ambient DOC in a coastal
      ecosystem. In three experiments, AltSIO alone consumed the entire pool of labile
      DOC, defined here as the quantity consumed by the submicron size fraction of
      ambient microbial assemblages within 5 d. These findings demonstrate that
      complete removal of the labile DOC pool in coastal surface seawater can be
      achieved by a single taxon. During long-term incubations (>1 y) testing
      semilabile DOC consumption, AltSIO entered dormancy but remained viable, while
      the diverse assemblages continued to consume carbon. Given that AltSIO is a large
      bacterium and thus subject to increased grazing pressure, we sought to determine
      the ecological relevance of this phenotype. Growth dynamics in natural seawater
      revealed that AltSIO rapidly outgrew the native bacteria, and despite intense
      grazing pressure, was never eliminated from the population. A survey in the
      California Current Ecosystem revealed that large bacteria (>=40 fg C?cell(-1))
      were persistent, accounting for up to 12% of total bacterial abundance and 24% of
      total bacterial biomass. We conclude that large, rapidly growing bacteria have
      the potential to disproportionately alter the fate of carbon in the mesotrophic
      ocean and play an important role in ecosystem function. 

PMID- 24733922
TI  - Host-derived, pore-forming toxin-like protein and trefoil factor complex protects
      the host against microbial infection.
AB  - Aerolysins are virulence factors belonging to the bacterial beta-pore-forming
      toxin superfamily. Surprisingly, numerous aerolysin-like proteins exist in
      vertebrates, but their biological functions are unknown. betagamma-CAT, a complex
      of an aerolysin-like protein subunit (two betagamma-crystallin domains followed
      by an aerolysin pore-forming domain) and two trefoil factor subunits, has been
      identified in frogs (Bombina maxima) skin secretions. Here, we report the rich
      expression of this protein, in the frog blood and immune-related tissues, and the
      induction of its presence in peritoneal lavage by bacterial challenge. This
      phenomena raises the possibility of its involvement in antimicrobial infection.
      When betagamma-CAT was administrated in a peritoneal infection model, it greatly
      accelerated bacterial clearance and increased the survival rate of both frogs and
      mice. Meanwhile, accelerated Interleukin-1beta release and enhanced local
      leukocyte recruitments were determined, which may partially explain the robust
      and effective antimicrobial responses observed. The release of interleukin-1beta
      was potently triggered by betagamma-CAT from the frog peritoneal cells and murine
      macrophages in vitro. betagamma-CAT was rapidly endocytosed and translocated to
      lysosomes, where it formed high molecular mass SDS-stable oligomers (>170 kDa).
      Lysosomal destabilization and cathepsin B release were detected, which may
      explain the activation of caspase-1 inflammasome and subsequent interleukin-1beta
      maturation and release. To our knowledge, these results provide the first
      functional evidence of the ability of a host-derived aerolysin-like protein to
      counter microbial infection by eliciting rapid and effective host innate immune
      responses. The findings will also largely help to elucidate the possible
      involvement and action mechanisms of aerolysin-like proteins and/or trefoil
      factors widely existing in vertebrates in the host defense against pathogens. 

PMID- 24733923
TI  - Assessing the effects of anthropogenic aerosols on Pacific storm track using a
      multiscale global climate model.
AB  - Atmospheric aerosols affect weather and global general circulation by modifying
      cloud and precipitation processes, but the magnitude of cloud adjustment by
      aerosols remains poorly quantified and represents the largest uncertainty in
      estimated forcing of climate change. Here we assess the effects of anthropogenic
      aerosols on the Pacific storm track, using a multiscale global aerosol-climate
      model (GCM). Simulations of two aerosol scenarios corresponding to the present
      day and preindustrial conditions reveal long-range transport of anthropogenic
      aerosols across the north Pacific and large resulting changes in the aerosol
      optical depth, cloud droplet number concentration, and cloud and ice water paths.
      Shortwave and longwave cloud radiative forcing at the top of atmosphere are
      changed by -2.5 and +1.3 W m(-2), respectively, by emission changes from
      preindustrial to present day, and an increased cloud top height indicates
      invigorated midlatitude cyclones. The overall increased precipitation and
      poleward heat transport reflect intensification of the Pacific storm track by
      anthropogenic aerosols. Hence, this work provides, for the first time to the
      authors' knowledge, a global perspective of the effects of Asian pollution
      outflows from GCMs. Furthermore, our results suggest that the multiscale modeling
      framework is essential in producing the aerosol invigoration effect of deep
      convective clouds on a global scale. 

PMID- 24733925
TI  - Secretion of von Willebrand factor by endothelial cells links sodium to
      hypercoagulability and thrombosis.
AB  - Hypercoagulability increases risk of thrombi that cause cardiovascular events.
      Here we identify plasma sodium concentration as a factor that modulates blood
      coagulability by affecting the production of von Willebrand factor (vWF), a key
      initiator of the clotting cascade. We find that elevation of salt over a range
      from the lower end of what is normal in blood to the level of severe
      hypernatremia reversibly increases vWF mRNA in endothelial cells in culture and
      the rate of vWF secretion from them. The high NaCl increases expression of
      tonicity-regulated transcription factor NFAT5 and its binding to promoter of vWF
      gene, suggesting involvement of hypertonic signaling in vWF up-regulation. To
      elevate NaCl in vivo, we modeled mild dehydration, subjecting mice to water
      restriction (WR) by feeding them with gel food containing 30% water. Such WR
      elevates blood sodium from 145.1 +/- 0.5 to 150.2 +/- 1.3 mmol/L and activates
      hypertonic signaling, evidenced from increased expression of NFAT5 in tissues. WR
      increases vWF mRNA in liver and lung and raises vWF protein in blood.
      Immunostaining of liver revealed increased production of vWF protein by
      endothelium and increased number of microthrombi inside capillaries. WR also
      increases blood level of D-dimer, indicative of ongoing coagulation and
      thrombolysis. Multivariate regression analysis of clinical data from the
      Atherosclerosis Risk in Communities Study demonstrated that serum sodium
      significantly contributes to prediction of plasma vWF and risk of stroke. The
      results indicate that elevation of extracellular sodium within the physiological
      range raises vWF sufficiently to increase coagulability and risk of thrombosis. 

PMID- 24733924
TI  - Prevention of influenza by targeting host receptors using engineered proteins.
AB  - There is a need for new approaches for the control of influenza given the burden
      caused by annual seasonal outbreaks, the emergence of viruses with pandemic
      potential, and the development of resistance to current antiviral drugs. We show
      that multivalent biologics, engineered using carbohydrate-binding modules
      specific for sialic acid, mask the cell-surface receptor recognized by the
      influenza virus and protect mice from a lethal challenge with 2009 pandemic H1N1
      influenza virus. The most promising biologic protects mice when given as a single
      1-MUg intranasal dose 7 d in advance of viral challenge. There also is sufficient
      virus replication to establish an immune response, potentially protecting the
      animal from future exposure to the virus. Furthermore, the biologics appear to
      stimulate inflammatory mediators, and this stimulation may contribute to their
      protective ability. Our results suggest that this host-targeted approach could
      provide a front-line prophylactic that has the potential to protect against any
      current and future influenza virus and possibly against other respiratory
      pathogens that use sialic acid as a receptor. 

PMID- 24733926
TI  - [2Fe-2S] cluster transfer in iron-sulfur protein biogenesis.
AB  - Monothiol glutaredoxins play a crucial role in iron-sulfur (Fe/S) protein
      biogenesis. Essentially all of them can coordinate a [2Fe-2S] cluster and have
      been proposed to mediate the transfer of [2Fe-2S] clusters from scaffold proteins
      to target apo proteins, possibly by acting as cluster transfer proteins. The
      molecular basis of [2Fe-2S] cluster transfer from monothiol glutaredoxins to
      target proteins is a fundamental, but still unresolved, aspect to be defined in
      Fe/S protein biogenesis. In mitochondria monothiol glutaredoxin 5 (GRX5) is
      involved in the maturation of all cellular Fe/S proteins and participates in
      cellular iron regulation. Here we show that the structural plasticity of the
      dimeric state of the [2Fe-2S] bound form of human GRX5 (holo hGRX5) is the
      crucial factor that allows an efficient cluster transfer to the partner proteins
      human ISCA1 and ISCA2 by a specific protein-protein recognition mechanism. Holo
      hGRX5 works as a metallochaperone preventing the [2Fe-2S] cluster to be released
      in solution in the presence of physiological concentrations of glutathione and
      forming a transient, cluster-mediated protein-protein intermediate with two
      physiological protein partners receiving the [2Fe-2S] cluster. The cluster
      transfer mechanism defined here may extend to other mitochondrial [2Fe-2S] target
      proteins. 

PMID- 24733927
TI  - Toward a better understanding and quantification of methane emissions from shale
      gas development.
AB  - The identification and quantification of methane emissions from natural gas
      production has become increasingly important owing to the increase in the natural
      gas component of the energy sector. An instrumented aircraft platform was used to
      identify large sources of methane and quantify emission rates in southwestern PA
      in June 2012. A large regional flux, 2.0-14 g CH4 s(-1) km(-2), was quantified
      for a ~ 2,800-km(2) area, which did not differ statistically from a bottom-up
      inventory, 2.3-4.6 g CH4 s(-1) km(-2). Large emissions averaging 34 g CH4/s per
      well were observed from seven well pads determined to be in the drilling phase, 2
      to 3 orders of magnitude greater than US Environmental Protection Agency
      estimates for this operational phase. The emissions from these well pads,
      representing ~ 1% of the total number of wells, account for 4-30% of the observed
      regional flux. More work is needed to determine all of the sources of methane
      emissions from natural gas production, to ascertain why these emissions occur and
      to evaluate their climate and atmospheric chemistry impacts.

PMID- 24733928
TI  - Tumor microenvironment-based feed-forward regulation of NOS2 in breast cancer
      progression.
AB  - Inflammation is widely recognized as an inducer of cancer progression. The
      inflammation-associated enzyme, inducible nitric oxide synthase (NOS2), has
      emerged as a candidate oncogene in estrogen receptor (ER)-negative breast cancer,
      and its increased expression is associated with disease aggressiveness and poor
      survival. Although these observations implicate NOS2 as an attractive therapeutic
      target, the mechanisms of both NOS2 induction in tumors and nitric oxide (NO)
      driven cancer progression are not fully understood. To enhance our mechanistic
      understanding of NOS2 induction in tumors and its role in tumor biology, we used
      stimulants of NOS2 expression in ER(-) and ER(+) breast cancer cells and examined
      downstream NO-dependent effects. Herein, we show that up-regulation of NOS2
      occurs in response to hypoxia, serum withdrawal, IFN-gamma, and exogenous NO,
      consistent with a feed-forward regulation of NO production by the tumor
      microenvironment in breast cancer biology. Moreover, we found that key indicators
      of an aggressive cancer phenotype including increased S100 calcium binding
      protein A8, IL-6, IL-8, and tissue inhibitor matrix metalloproteinase-1 are up
      regulated by these NOS2 stimulants, whereas inhibition of NOS2 in MDA-MB-231
      breast cancer cells suppressed these markers. Moreover, NO altered cellular
      migration and chemoresistance of MDA-MB-231 cells to Taxol. Most notably, MDA-MB
      231 tumor xenographs and cell metastases from the fat pad to the brain were
      significantly suppressed by NOS2 inhibition in nude mice. In summary, these
      results link elevated NOS2 to signals from the tumor microenvironment that arise
      with cancer progression and show that NO production regulates chemoresistance and
      metastasis of breast cancer cells. 

PMID- 24733929
TI  - Mapping the stochastic response of nanostructures.
AB  - Nanostructures are technological devices constructed on a nanometer length scale
      more than a thousand times thinner than a human hair. Due to the unique
      properties of matter at this scale, such devices offer great potential for
      creating novel materials and behaviors that can be leveraged to benefit mankind.
      This paper addresses a particular challenge involved in the design of
      nanostructures--their stochastic or apparently random response to external
      loading. This is because fundamentally the function that relates the energy of a
      nanostructure to the arrangement of its atoms is extremely nonconvex, with each
      minimum corresponding to a possible equilibrium state that may be visited as the
      system responds to loading. Traditional atomistic simulation techniques are not
      capable of systematically addressing this complexity. Instead, we construct an
      equilibrium map (EM) for the nanostructure, analogous to a phase diagram for bulk
      materials, which fully characterizes its response. Using the EM, definitive
      predictions can be made in limiting cases and the spectrum of responses at any
      desired loading rate can be obtained. The latter is important because standard
      atomistic methods are fundamentally limited, by computational feasibility, to
      simulations of loading rates that are many orders of magnitude faster than
      reality. In contrast, the EM-based approach makes possible the direct simulation
      of nanostructure experiments. We demonstrate the method's capabilities and its
      surprisingly complex results for the case of a nanoslab of nickel under
      compression.

PMID- 24733930
TI  - (Finite) statistical size effects on compressive strength.
AB  - The larger structures are, the lower their mechanical strength. Already discussed
      by Leonardo da Vinci and Edme Mariotte several centuries ago, size effects on
      strength remain of crucial importance in modern engineering for the elaboration
      of safety regulations in structural design or the extrapolation of laboratory
      results to geophysical field scales. Under tensile loading, statistical size
      effects are traditionally modeled with a weakest-link approach. One of its
      prominent results is a prediction of vanishing strength at large scales that can
      be quantified in the framework of extreme value statistics. Despite a frequent
      use outside its range of validity, this approach remains the dominant tool in the
      field of statistical size effects. Here we focus on compressive failure, which
      concerns a wide range of geophysical and geotechnical situations. We show on
      historical and recent experimental data that weakest-link predictions are not
      obeyed. In particular, the mechanical strength saturates at a nonzero value
      toward large scales. Accounting explicitly for the elastic interactions between
      defects during the damage process, we build a formal analogy of compressive
      failure with the depinning transition of an elastic manifold. This critical
      transition interpretation naturally entails finite-size scaling laws for the mean
      strength and its associated variability. Theoretical predictions are in
      remarkable agreement with measurements reported for various materials such as
      rocks, ice, coal, or concrete. This formalism, which can also be extended to the
      flowing instability of granular media under multiaxial compression, has important
      practical consequences for future design rules. 

PMID- 24733931
TI  - Avirulent strains of Toxoplasma gondii infect macrophages by active invasion from
      the phagosome.
AB  - Unlike most intracellular pathogens that gain access into host cells through
      endocytic pathways, Toxoplasma gondii initiates infection at the cell surface by
      active penetration through a moving junction and subsequent formation of a
      parasitophorous vacuole. Here, we describe a noncanonical pathway for T. gondii
      infection of macrophages, in which parasites are initially internalized through
      phagocytosis, and then actively invade from within a phagosomal compartment to
      form a parasitophorous vacuole. This phagosome to vacuole invasion (PTVI) pathway
      may represent an intermediary link between the endocytic and the penetrative
      routes for host cell entry by intracellular pathogens. The PTVI pathway is
      preferentially used by avirulent strains of T. gondii and confers an infectious
      advantage over virulent strains for macrophage tropism. 

PMID- 24733932
TI  - Low glucose relates to greater aggression in married couples.
AB  - Intimate partner violence affects millions of people globally. One possible
      contributing factor is poor self-control. Self-control requires energy, part of
      which is provided by glucose. For 21 days, glucose levels were measured in 107
      married couples. To measure aggressive impulses, each evening participants stuck
      between 0 and 51 pins into a voodoo doll that represented their spouse, depending
      how angry they were with their spouse. To measure aggression, participants
      competed against their spouse on a 25-trial task in which the winner blasted the
      loser with loud noise through headphones. As expected, the lower the level of
      glucose in the blood, the greater number of pins participants stuck into the
      voodoo doll, and the higher intensity and longer duration of noise participants
      set for their spouse. 

PMID- 24733933
TI  - Structure of the Toll-Spatzle complex, a molecular hub in Drosophila development
      and innate immunity.
AB  - Drosophila Toll receptors are involved in embryonic development and the immune
      response of adult flies. In both processes, the only known Toll receptor ligand
      is the human nerve growth factor-like cystine knot protein Spatzle. Here we
      present the crystal structure of a 1:1 (nonsignaling) complex of the full-length
      Toll receptor ectodomain (ECD) with the Spatzle cystine knot domain dimer. The
      ECD is divided into two leucine-rich repeat (LRR) domains, each of which is
      capped by cysteine-rich domains. Spatzle binds to the concave surface of the
      membrane-distal LRR domain, in contrast to the flanking ligand interactions
      observed for mammalian Toll-like receptors, with asymmetric contributions from
      each Spatzle protomer. The structure allows rationalization of existing genetic
      and biochemical data and provides a framework for targeting the immune systems of
      insects of economic importance, as well as a variety of invertebrate disease
      vectors. 

PMID- 24733934
TI  - Defining modulatory inputs into CNS neuronal subclasses by functional
      pharmacological profiling.
AB  - Previously we defined neuronal subclasses within the mouse peripheral nervous
      system using an experimental strategy called "constellation pharmacology." Here
      we demonstrate the broad applicability of constellation pharmacology by extending
      it to the CNS and specifically to the ventral respiratory column (VRC) of mouse
      brainstem, a region containing the neuronal network controlling respiratory
      rhythm. Analysis of dissociated cells from this locus revealed three major cell
      classes, each encompassing multiple subclasses. We broadly analyzed the
      combinations (constellations) of receptors and ion channels expressed within VRC
      cell classes and subclasses. These were strikingly different from the
      constellations of receptors and ion channels found in subclasses of peripheral
      neurons from mouse dorsal root ganglia. Within the VRC cell population, a subset
      of dissociated neurons responded to substance P, putatively corresponding to
      inspiratory pre-Botzinger complex (preBotC) neurons. Using constellation
      pharmacology, we found that these substance P-responsive neurons also responded
      to histamine, and about half responded to bradykinin. Electrophysiological
      studies conducted in brainstem slices confirmed that preBotC neurons responsive
      to substance P exhibited similar responsiveness to bradykinin and histamine. The
      results demonstrate the predictive utility of constellation pharmacology for
      defining modulatory inputs into specific neuronal subclasses within central
      neuronal networks. 

PMID- 24733935
TI  - Light intensity modulates the regulatory network of the shade avoidance response
      in Arabidopsis.
AB  - Plants such as Arabidopsis thaliana respond to foliar shade and neighbors who may
      become competitors for light resources by elongation growth to secure access to
      unfiltered sunlight. Challenges faced during this shade avoidance response (SAR)
      are different under a light-absorbing canopy and during neighbor detection where
      light remains abundant. In both situations, elongation growth depends on auxin
      and transcription factors of the phytochrome interacting factor (PIF) class.
      Using a computational modeling approach to study the SAR regulatory network, we
      identify and experimentally validate a previously unidentified role for long
      hypocotyl in far red 1, a negative regulator of the PIFs. Moreover, we find that
      during neighbor detection, growth is promoted primarily by the production of
      auxin. In contrast, in true shade, the system operates with less auxin but with
      an increased sensitivity to the hormonal signal. Our data suggest that this
      latter signal is less robust, which may reflect a cost-to-robustness tradeoff, a
      system trait long recognized by engineers and forming the basis of information
      theory. 

PMID- 24733936
TI  - Partner choice and fidelity stabilize coevolution in a Cretaceous-age defensive
      symbiosis.
AB  - Many insects rely on symbiotic microbes for survival, growth, or reproduction.
      Over evolutionary timescales, the association with intracellular symbionts is
      stabilized by partner fidelity through strictly vertical symbiont transmission,
      resulting in congruent host and symbiont phylogenies. However, little is known
      about how symbioses with extracellular symbionts, representing the majority of
      insect-associated microorganisms, evolve and remain stable despite opportunities
      for horizontal exchange and de novo acquisition of symbionts from the
      environment. Here we demonstrate that host control over symbiont transmission
      (partner choice) reinforces partner fidelity between solitary wasps and
      antibiotic-producing bacteria and thereby stabilizes this Cretaceous-age
      defensive mutualism. Phylogenetic analyses show that three genera of beewolf
      wasps (Philanthus, Trachypus, and Philanthinus) cultivate a distinct clade of
      Streptomyces bacteria for protection against pathogenic fungi. The symbionts were
      acquired from a soil-dwelling ancestor at least 68 million years ago, and
      vertical transmission via the brood cell and the cocoon surface resulted in host
      symbiont codiversification. However, the external mode of transmission also
      provides opportunities for horizontal transfer, and beewolf species have indeed
      exchanged symbiont strains, possibly through predation or nest reuse.
      Experimental infection with nonnative bacteria reveals that--despite successful
      colonization of the antennal gland reservoirs--transmission to the cocoon is
      selectively blocked. Thus, partner choice can play an important role even in
      predominantly vertically transmitted symbioses by stabilizing the cooperative
      association over evolutionary timescales.

PMID- 24733937
TI  - Abrupt increases in Amazonian tree mortality due to drought-fire interactions.
AB  - Interactions between climate and land-use change may drive widespread degradation
      of Amazonian forests. High-intensity fires associated with extreme weather events
      could accelerate this degradation by abruptly increasing tree mortality, but this
      process remains poorly understood. Here we present, to our knowledge, the first
      field-based evidence of a tipping point in Amazon forests due to altered fire
      regimes. Based on results of a large-scale, long-term experiment with annual and
      triennial burn regimes (B1yr and B3yr, respectively) in the Amazon, we found
      abrupt increases in fire-induced tree mortality (226 and 462%) during a severe
      drought event, when fuel loads and air temperatures were substantially higher and
      relative humidity was lower than long-term averages. This threshold mortality
      response had a cascading effect, causing sharp declines in canopy cover (23 and
      31%) and aboveground live biomass (12 and 30%) and favoring widespread invasion
      by flammable grasses across the forest edge area (80 and 63%), where fires were
      most intense (e.g., 220 and 820 kW ? m(-1)). During the droughts of 2007 and
      2010, regional forest fires burned 12 and 5% of southeastern Amazon forests,
      respectively, compared with <1% in nondrought years. These results show that a
      few extreme drought events, coupled with forest fragmentation and anthropogenic
      ignition sources, are already causing widespread fire-induced tree mortality and
      forest degradation across southeastern Amazon forests. Future projections of
      vegetation responses to climate change across drier portions of the Amazon
      require more than simulation of global climate forcing alone and must also
      include interactions of extreme weather events, fire, and land-use change.

PMID- 24733938
TI  - Lipopolysaccharide O antigen size distribution is determined by a chain extension
      complex of variable stoichiometry in Escherichia coli O9a.
AB  - The lengths of bacterial polysaccharides can be critical for their biological
      function. Unlike DNA or protein synthesis, where polymer length is implicit in
      the nucleic acid template, the molecular mechanisms for regulating polysaccharide
      length are poorly understood. Two models are commonly cited: a "molecular clock"
      regulates length by controlling the duration of the polymer extension process,
      whereas a "molecular ruler" determines length by measurement against a physical
      structure in the biosynthetic complex. Escherichia coli O9a is a prototype for
      the biosynthesis of O polysaccharides by ATP-binding cassette transporter
      dependent processes. The length of the O9a polysaccharide is determined by two
      proteins: an extension enzyme, WbdA, and a termination enzyme, WbdD. WbdD is
      known to self-oligomerize and also to interact with WbdA. Changing either
      enzyme's concentration can alter the polysaccharide length. We quantified the O9a
      polysaccharide length distribution and the enzyme concentration dependence in
      vivo, then made mathematical models to predict the polymer length distributions
      resulting from hypothetical length-regulation mechanisms. Our data show
      qualitative features that cannot be explained by either a molecular clock or a
      molecular ruler model. Therefore, we propose a "variable geometry" model, in
      which a postulated biosynthetic WbdA-WbdD complex assembles with variable
      stoichiometry dependent on relative enzyme concentration. Each stoichiometry
      produces polymers with a distinct, geometrically determined, modal length. This
      model reproduces the enzyme concentration dependence and modality of the observed
      polysaccharide length distributions. Our work highlights limitations of previous
      models and provides new insight into the mechanisms of length control in
      polysaccharide biosynthesis. 

PMID- 24733939
TI  - Training-free atomistic prediction of nucleosome occupancy.
AB  - Nucleosomes alter gene expression by preventing transcription factors from
      occupying binding sites along DNA. DNA methylation can affect nucleosome
      positioning and so alter gene expression epigenetically (without changing DNA
      sequence). Conventional methods to predict nucleosome occupancy are trained on
      observed DNA sequence patterns or known DNA oligonucleotide structures. They are
      statistical and lack the physics needed to predict subtle epigenetic changes due
      to DNA methylation. The training-free method presented here uses physical
      principles and state-of-the-art all-atom force fields to predict both nucleosome
      occupancy along genomic sequences as well as binding to known positioning
      sequences. Our method calculates the energy of both nucleosomal and linear DNA of
      the given sequence. Based on the DNA deformation energy, we accurately predict
      the in vitro occupancy profile observed experimentally for a 20,000-bp genomic
      region as well as the experimental locations of nucleosomes along 13 well
      established positioning sequence elements. DNA with all C bases methylated at the
      5 position shows less variation of nucleosome binding: Strong binding is weakened
      and weak binding is strengthened compared with normal DNA. Methylation also
      alters the preference of nucleosomes for some positioning sequences but not
      others. 

PMID- 24733940
TI  - Cellular heterogeneity profiling by hyaluronan probes reveals an invasive but
      slow-growing breast tumor subset.
AB  - Tumor heterogeneity confounds cancer diagnosis and the outcome of therapy,
      necessitating analysis of tumor cell subsets within the tumor mass. Elevated
      expression of hyaluronan (HA) and HA receptors, receptor for HA-mediated motility
      (RHAMM)/HA-mediated motility receptor and cluster designation 44 (CD44), in
      breast tumors correlates with poor outcome. We hypothesized that a probe for
      detecting HA-HA receptor interactions may reveal breast cancer (BCa) cell
      heterogeneity relevant to tumor progression. A fluorescent HA (F-HA) probe
      containing a mixture of polymer sizes typical of tumor microenvironments (10-480
      kDa), multiplexed profiling, and flow cytometry were used to monitor HA binding
      to BCa cell lines of different molecular subtypes. Formulae were developed to
      quantify binding heterogeneity and to measure invasion in vivo. Two subsets
      exhibiting differential binding (HA(-/low) vs. HA(high)) were isolated and
      characterized for morphology, growth, and invasion in culture and as xenografts
      in vivo. F-HA-binding amounts and degree of heterogeneity varied with BCa
      subtype, were highest in the malignant basal-like cell lines, and decreased upon
      reversion to a nonmalignant phenotype. Binding amounts correlated with CD44 and
      RHAMM displayed but binding heterogeneity appeared to arise from a differential
      ability of HA receptor-positive subpopulations to interact with F-HA. HA(high)
      subpopulations exhibited significantly higher local invasion and lung
      micrometastases but, unexpectedly, lower proliferation than either unsorted
      parental cells or the HA(-/low) subpopulation. Querying F-HA binding to
      aggressive tumor cells reveals a previously undetected form of heterogeneity that
      predicts invasive/metastatic behavior and that may aid both early identification
      of cancer patients susceptible to metastasis, and detection/therapy of invasive
      BCa subpopulations. 

PMID- 24733941
TI  - Glioblastoma cellular architectures are predicted through the characterization of
      two-cell interactions.
AB  - To understand how pairwise cellular interactions influence cellular
      architectures, we measured the levels of functional proteins associated with EGF
      receptor (EGFR) signaling in pairs of U87EGFR variant III oncogene receptor cells
      (U87EGFRvIII) at varying cell separations. Using a thermodynamics-derived
      approach we analyzed the cell-separation dependence of the signaling stability,
      and identified that the stable steady state of EGFR signaling exists when two
      U87EGFRvIII cells are separated by 80-100 MUm. This distance range was verified
      as the characteristic intercellular separation within bulk cell cultures. EGFR
      protein network signaling coordination for the U87EGFRvIII system was lowest at
      the stable state and most similar to isolated cell signaling. Measurements of
      cultures of less tumorigenic U87PTEN cells were then used to correctly predict
      that stable EGFR signaling occurs for those cells at smaller cell-cell
      separations. The intimate relationship between functional protein levels and
      cellular architectures explains the scattered nature of U87EGFRvIII cells
      relative to U87PTEN cells in glioblastoma multiforme tumors. 

PMID- 24733942
TI  - Reactive cysteine persulfides and S-polythiolation regulate oxidative stress and
      redox signaling.
AB  - Using methodology developed herein, it is found that reactive persulfides and
      polysulfides are formed endogenously from both small molecule species and
      proteins in high amounts in mammalian cells and tissues. These reactive sulfur
      species were biosynthesized by two major sulfurtransferases: cystathionine beta
      synthase and cystathionine gamma-lyase. Quantitation of these species indicates
      that high concentrations of glutathione persulfide (perhydropersulfide >100 MUM)
      and other cysteine persulfide and polysulfide derivatives in peptides/proteins
      were endogenously produced and maintained in the plasma, cells, and tissues of
      mammals (rodent and human). It is expected that persulfides are especially
      nucleophilic and reducing. This view was found to be the case, because they
      quickly react with H2O2 and a recently described biologically generated
      electrophile 8-nitroguanosine 3',5'-cyclic monophosphate. These results indicate
      that persulfides are potentially important signaling/effector species, and
      because H2S can be generated from persulfide degradation, much of the reported
      biological activity associated with H2S may actually be that of persulfides. That
      is, H2S may act primarily as a marker for the biologically active of persulfide
      species. 

PMID- 24733944
TI  - Raoultella planticola-associated cholangitis and sepsis: a case report and
      literature review.

PMID- 24733943
TI  - Stretched cell cycle model for proliferating lymphocytes.
AB  - Stochastic variation in cell cycle time is a consistent feature of otherwise
      similar cells within a growing population. Classic studies concluded that the
      bulk of the variation occurs in the G1 phase, and many mathematical models assume
      a constant time for traversing the S/G2/M phases. By direct observation of
      transgenic fluorescent fusion proteins that report the onset of S phase, we
      establish that dividing B and T lymphocytes spend a near-fixed proportion of
      total division time in S/G2/M phases, and this proportion is correlated between
      sibling cells. This result is inconsistent with models that assume independent
      times for consecutive phases. Instead, we propose a stretching model for dividing
      lymphocytes where all parts of the cell cycle are proportional to total division
      time. Data fitting based on a stretched cell cycle model can significantly
      improve estimates of cell cycle parameters drawn from DNA labeling data used to
      monitor immune cell dynamics. 

PMID- 24733945
TI  - Satellite remote sensing, biodiversity research and conservation of the future.
AB  - Assessing and predicting ecosystem responses to global environmental change and
      its impacts on human well-being are high priority targets for the scientific
      community. The potential for synergies between remote sensing science and
      ecology, especially satellite remote sensing and conservation biology, has been
      highlighted by many in the past. Yet, the two research communities have only
      recently begun to coordinate their agendas. Such synchronization is the key to
      improving the potential for satellite data effectively to support future
      environmental management decision-making processes. With this themed issue, we
      aim to illustrate how integrating remote sensing into ecological research
      promotes a better understanding of the mechanisms shaping current changes in
      biodiversity patterns and improves conservation efforts. Added benefits include
      fostering innovation, generating new research directions in both disciplines and
      the development of new satellite remote sensing products. 

PMID- 24733946
TI  - Oil in the Sahara: mapping anthropogenic threats to Saharan biodiversity from
      space.
AB  - Deserts are among the most poorly monitored and understood biomes in the world,
      with evidence suggesting that their biodiversity is declining fast. Oil
      exploration and exploitation can constitute an important threat to fragmented and
      remnant desert biodiversity, yet little is known about where and how intensively
      such developments are taking place. This lack of information hinders local
      efforts to adequately buffer and protect desert wildlife against encroachment
      from anthropogenic activity. Here, we investigate the use of freely available
      satellite imagery for the detection of features associated with oil exploration
      in the African Sahelo-Saharan region. We demonstrate how texture analyses
      combined with Landsat data can be employed to detect ground-validated exploration
      sites in Algeria and Niger. Our results show that site detection via supervised
      image classification and prediction is generally accurate. One surprising outcome
      of our analyses is the relatively high level of site omission errors in Niger
      (43%), which appears to be due to non-detection of potentially small-scale,
      temporary exploration activity: we believe the repeated implementation of our
      framework could reduce the severity of potential methodological limitations.
      Overall, our study provides a methodological basis for the mapping of
      anthropogenic threats associated with oil exploitation that can be conducted
      across desert regions. 

PMID- 24733947
TI  - Assessing current and projected suitable habitats for tree-of-heaven along the
      Appalachian Trail.
AB  - The invasion of ecosystems by non-native species is a major driver of
      biodiversity loss worldwide. A critical component of effective land management to
      control invasion is the identification and active protection of areas at high
      risk of future invasion. The Appalachian Trail Decision Support System (A.T.-DSS)
      was developed to inform regional natural resource management by integrating
      remote sensing data, ground-based measurements and predictive modelling products.
      By incorporating NASA's remote sensing data and modelling capacities from the
      Terrestrial Observation and Prediction System (TOPS), this study examined the
      current habitat suitability and projected suitable habitat for the invasive
      species tree-of-heaven (Ailanthus altissima) as a prototype application of the
      A.T.-DSS. Species observations from forest surveys, geospatial data, climatic
      projections and maximum entropy modelling were used to identify regions
      potentially susceptible to tree-of-heaven invasion. The modelling result
      predicted a 48% increase in suitable area over the study area, with significant
      expansion along the northern extremes of the Appalachian Trail. 

PMID- 24733948
TI  - Role of African protected areas in maintaining connectivity for large mammals.
AB  - The African protected area (PA) network has the potential to act as a set of
      functionally interconnected patches that conserve meta-populations of mammal
      species, but individual PAs are vulnerable to habitat change which may disrupt
      connectivity and increase extinction risk. Individual PAs have different roles in
      maintaining connectivity, depending on their size and location. We measured their
      contribution to network connectivity (irreplaceability) for carnivores and
      ungulates and combined it with a measure of vulnerability based on a 30-year
      trend in remotely sensed vegetation cover (Normalized Difference Vegetation
      Index). Highly irreplaceable PAs occurred mainly in southern and eastern Africa.
      Vegetation cover change was generally faster outside than inside PAs and
      particularly so in southern Africa. The extent of change increased with the
      distance from PAs. About 5% of highly irreplaceable PAs experienced a faster
      vegetation cover loss than their surroundings, thus requiring particular
      conservation attention. Our analysis identified PAs at risk whose isolation would
      disrupt the connectivity of the PA network for large mammals. This is an example
      of how ecological spatial modelling can be combined with large-scale remote
      sensing data to investigate how land cover change may affect ecological processes
      and species conservation. 

PMID- 24733949
TI  - Imaging spectroscopy links aspen genotype with below-ground processes at
      landscape scales.
AB  - Fine-scale biodiversity is increasingly recognized as important to ecosystem
      level processes. Remote sensing technologies have great potential to estimate
      both biodiversity and ecosystem function over large spatial scales. Here, we
      demonstrate the capacity of imaging spectroscopy to discriminate among genotypes
      of Populus tremuloides (trembling aspen), one of the most genetically diverse and
      widespread forest species in North America. We combine imaging spectroscopy
      (AVIRIS) data with genetic, phytochemical, microbial and biogeochemical data to
      determine how intraspecific plant genetic variation influences below-ground
      processes at landscape scales. We demonstrate that both canopy chemistry and
      below-ground processes vary over large spatial scales (continental) according to
      aspen genotype. Imaging spectrometer data distinguish aspen genotypes through
      variation in canopy spectral signature. In addition, foliar spectral variation
      correlates well with variation in canopy chemistry, especially condensed tannins.
      Variation in aspen canopy chemistry, in turn, is correlated with variation in
      below-ground processes. Variation in spectra also correlates well with variation
      in soil traits. These findings indicate that forest tree species can create
      spatial mosaics of ecosystem functioning across large spatial scales and that
      these patterns can be quantified via remote sensing techniques. Moreover, they
      demonstrate the utility of using optical properties as proxies for fine-scale
      measurements of biodiversity over large spatial scales. 

PMID- 24733950
TI  - Environmental drivers of variability in the movement ecology of turkey vultures
      (Cathartes aura) in North and South America.
AB  - Variation is key to the adaptability of species and their ability to survive
      changes to the Earth's climate and habitats. Plasticity in movement strategies
      allows a species to better track spatial dynamics of habitat quality. We describe
      the mechanisms that shape the movement of a long-distance migrant bird (turkey
      vulture, Cathartes aura) across two continents using satellite tracking coupled
      with remote-sensing science. Using nearly 10 years of data from 24 satellite
      tracked vultures in four distinct populations, we describe an enormous amount of
      variation in their movement patterns. We related vulture movement to
      environmental conditions and found important correlations explaining how far they
      need to move to find food (indexed by the Normalized Difference Vegetation Index)
      and how fast they can move based on the prevalence of thermals and temperature.
      We conclude that the extensive variability in the movement ecology of turkey
      vultures, facilitated by their energetically efficient thermal soaring, suggests
      that this species is likely to do well across periods of modest climate change.
      The large scale and sample sizes needed for such analysis in a widespread migrant
      emphasizes the need for integrated and collaborative efforts to obtain tracking
      data and for policies, tools and open datasets to encourage such collaborations
      and data sharing. 

PMID- 24733951
TI  - Functional analysis of normalized difference vegetation index curves reveals
      overwinter mule deer survival is driven by both spring and autumn phenology.
AB  - Large herbivore populations respond strongly to remotely sensed measures of
      primary productivity. Whereas most studies in seasonal environments have focused
      on the effects of spring plant phenology on juvenile survival, recent studies
      demonstrated that autumn nutrition also plays a crucial role. We tested for both
      direct and indirect (through body mass) effects of spring and autumn phenology on
      winter survival of 2315 mule deer fawns across a wide range of environmental
      conditions in Idaho, USA. We first performed a functional analysis that
      identified spring and autumn as the key periods for structuring the among
      population and among-year variation of primary production (approximated from 1 km
      Advanced Very High Resolution Radiometer Normalized Difference Vegetation Index
      (NDVI)) along the growing season. A path analysis showed that early winter
      precipitation and direct and indirect effects of spring and autumn NDVI
      functional components accounted for 45% of observed variation in overwinter
      survival. The effect size of autumn phenology on body mass was about twice that
      of spring phenology, while direct effects of phenology on survival were similar
      between spring and autumn. We demonstrate that the effects of plant phenology
      vary across ecosystems, and that in semi-arid systems, autumn may be more
      important than spring for overwinter survival. 

PMID- 24733952
TI  - Modelling avian biodiversity using raw, unclassified satellite imagery.
AB  - Applications of remote sensing for biodiversity conservation typically rely on
      image classifications that do not capture variability within coarse land cover
      classes. Here, we compare two measures derived from unclassified remotely sensed
      data, a measure of habitat heterogeneity and a measure of habitat composition,
      for explaining bird species richness and the spatial distribution of 10 species
      in a semi-arid landscape of New Mexico. We surveyed bird abundance from 1996 to
      1998 at 42 plots located in the McGregor Range of Fort Bliss Army Reserve.
      Normalized Difference Vegetation Index values of two May 1997 Landsat scenes were
      the basis for among-pixel habitat heterogeneity (image texture), and we used the
      raw imagery to decompose each pixel into different habitat components (spectral
      mixture analysis). We used model averaging to relate measures of avian
      biodiversity to measures of image texture and spectral mixture analysis
      fractions. Measures of habitat heterogeneity, particularly angular second moment
      and standard deviation, provide higher explanatory power for bird species
      richness and the abundance of most species than measures of habitat composition.
      Using image texture, alone or in combination with other classified imagery-based
      approaches, for monitoring statuses and trends in biological diversity can
      greatly improve conservation efforts and habitat management. 

PMID- 24733953
TI  - Drivers of extinction risk in African mammals: the interplay of distribution
      state, human pressure, conservation response and species biology.
AB  - Although conservation intervention has reversed the decline of some species, our
      success is outweighed by a much larger number of species moving towards
      extinction. Extinction risk modelling can identify correlates of risk and species
      not yet recognized to be threatened. Here, we use machine learning models to
      identify correlates of extinction risk in African terrestrial mammals using a set
      of variables belonging to four classes: species distribution state, human
      pressures, conservation response and species biology. We derived information on
      distribution state and human pressure from satellite-borne imagery. Variables in
      all four classes were identified as important predictors of extinction risk, and
      interactions were observed among variables in different classes (e.g. level of
      protection, human threats, species distribution ranges). Species biology had a
      key role in mediating the effect of external variables. The model was 90%
      accurate in classifying extinction risk status of species, but in a few cases the
      observed and modelled extinction risk mismatched. Species in this condition might
      suffer from an incorrect classification of extinction risk (hence require
      reassessment). An increased availability of satellite imagery combined with
      improved resolution and classification accuracy of the resulting maps will play a
      progressively greater role in conservation monitoring. 

PMID- 24733954
TI  - The optimal power puzzle: scrutiny of the monotone likelihood ratio assumption in
      multiple testing.
AB  - In single hypothesis testing, power is a non-decreasing function of type I error
      rate; hence it is desirable to test at the nominal level exactly to achieve
      optimal power. The puzzle lies in the fact that for multiple testing, under the
      false discovery rate paradigm, such a monotonic relationship may not hold. In
      particular, exact false discovery rate control may lead to a less powerful
      testing procedure if a test statistic fails to fulfil the monotone likelihood
      ratio condition. In this article, we identify different scenarios wherein the
      condition fails and give caveats for conducting multiple testing in practical
      settings.

PMID- 24733955
TI  - Bodies of Data: Genomic Data and Bioscience Data Sharing.

PMID- 24733956
TI  - E-learning in a virtual science camp for urban youth.
AB  - The Virtual Science Camp (VSC) is a unique demonstration of synchronous e
      learning developed by Mentoring in Medicine (MIM). This paper reports on a pilot
      offering during the summer of 2012 that taught advanced biological concepts,
      healthy living and health care career opportunities to medically underserved
      urban youth. Livestream's interactive video technology was used to engage a
      diverse audience of mostly high school students at remote sites in a new two week
      instructional program that provided custom course content free of charge over the
      internet. We describe the technical and program preparations undertaken, their
      implementation, the IT environment, a multi-faceted evaluation plan, the results
      of the experiment, and lessons learned.

PMID- 24733957
TI  - Seminal fluid protein depletion and replenishment in the fruit fly, Drosophila
      melanogaster: an ELISA-based method for tracking individual ejaculates.
AB  - In many species, seminal fluid proteins (SFPs) affect female post-mating
      behavioral patterns, including sperm storage, egg laying, feeding, and remating.
      Yet, few studies have investigated the patterns of allocation, depletion, and
      replenishment of SFPs in male animals, despite the importance of these proteins
      to male and female reproductive success. To investigate such SFP dynamics, it is
      necessary to have a sensitive method for quantifying SFP levels in males and
      mated females. We developed such a method by adapting the enzyme-linked
      immunosorbent assay (ELISA) using anti-SFP antibodies. Here, we first use two
      Drosophila melanogaster SFPs (ovulin and sex peptide) to demonstrate that ELISAs
      provide accurate measures of SFP levels. We find that, consistent with previous
      data from Western blotting or immunofluorescence studies, levels of both ovulin
      and sex peptide decline in the mated female with time since mating, but they do
      so at different rates. We then use ELISAs to show that males become depleted of
      SFPs with repeated matings, but that previously mated males are able to transfer
      "virgin" levels of SFPs after 3 days of sexual inactivity. Finally, we
      demonstrate that ELISAs can detect SFPs from wild-caught D. melanogaster males
      and, thus, potentially can be used to track mating patterns in the wild. This
      method of measuring SFP dynamics can be used in a wide range of species to
      address questions related to male reproductive investment, female mating history,
      and variation in female post-mating behavioral changes.

PMID- 24733958
TI  - The beta-2-adrenoreceptor agonists, formoterol and indacaterol, but not
      salbutamol, effectively suppress the reactivity of human neutrophils in vitro.
AB  - The clinical relevance of the anti-inflammatory properties of beta-2 agonists
      remains contentious possibly due to differences in their molecular structures and
      agonist activities. The current study has compared the effects of 3 different
      categories of beta 2-agonists, namely, salbutamol (short-acting), formoterol
      (long-acting) and indacaterol (ultra-long-acting), at concentrations of 1-1000
      nM, with human blood neutrophils in vitro. Neutrophils were activated with either
      N-formyl-L-methionyl-L-leucyl-L-phenylalanine (fMLP, 1 uM) or platelet-activating
      factor (PAF, 200 nM) in the absence and presence of the beta 2-agonists followed
      by measurement of the generation of reactive oxygen species and leukotriene B4,
      release of elastase, and expression of the beta 2-integrin, CR3, using a
      combination of chemiluminescence, ELISA, colorimetric, and flow cytometric
      procedures respectively. These were correlated with alterations in the
      concentrations of intracellular cyclic-AMP and cytosolic Ca(2+). At the
      concentrations tested, formoterol and indacaterol caused equivalent, significant
      (P < 0.05 at 1-10 nM) dose-related inhibition of all of the pro-inflammatory
      activities tested, while salbutamol was much less effective (P < 0.05 at 100 nM
      and higher). Suppression of neutrophil reactivity was accompanied by elevations
      in intracellular cAMP and accelerated clearance of Ca(2+) from the cytosol of
      activated neutrophils. These findings demonstrate that beta 2-agonists vary with
      respect to their suppressive effects on activated neutrophils.

PMID- 24733959
TI  - Elevated plasma IL-37, IL-18, and IL-18BP concentrations in patients with acute
      coronary syndrome.
AB  - OBJECTIVE: More recently, evidence showed that the novel anti-inflammatory
      cytokine interleukin- (IL-) 37 was expressed in the foam-like cells of
      atherosclerotic coronary and carotid artery plaques, suggesting that IL-37 is
      involved in atherosclerosis-related diseases. However, the plasma levels of IL-37
      in patients with acute coronary syndrome (ACS, including unstable angina pectoris
      and acute myocardial infarction) have yet to be investigated. METHODS: Plasma IL
      37, IL-18, and IL-18BP levels were measured in 50 patients with stable angina
      pectoris (SAP), 75 patients with unstable angina pectoris (UAP), 67 patients with
      acute myocardial infarction (AMI), and 65 control patients. RESULTS: The plasma
      IL-37, IL-18, and IL-18BP levels were significantly increased in ACS patients
      compared to SAP and control patients. A correlation analysis showed that the
      plasma biomarker levels were positively correlated with each other and with the
      levels of C-reactive protein (CRP), N-terminal probrain natriuretic peptide (NT
      proBNP), and left ventricular end-diastolic dimension (LVEDD) but negatively
      correlated with left ventricular ejection fraction (LVEF). Furthermore, the
      plasma IL-37, IL-18, and IL-18BP had no correlation with the severity of the
      coronary artery stenosis. CONCLUSIONS: The results indicate that the plasma IL-37
      levels are associated with the onset of ACS.

PMID- 24733960
TI  - The first trimester gravid serum regulates procalcitonin expression in human
      macrophages skewing their phenotype in vitro.
AB  - Procalcitonin (PCT) is one of the best diagnostic and prognostic markers in
      clinical practice, widely used to evaluate the evolution of bacterial infections.
      Although it is mainly produced by thyroid, during sepsis almost all the
      peripheral tissues are involved in PCT production. Parenchymal cells have been
      suggested as the main source of PCT expression; however the contribution of
      macrophages is not clear yet. In response to environmental cues, tissue
      macrophages acquire distinct functional phenotypes, ranging from proinflammatory
      (M1) to anti-inflammatory (M2) phenotype. Macrophages at the fetal-maternal
      interface show immunosuppressive M2-like activities required for the maintenance
      of immunological homeostasis during pregnancy. This study aims to clarify the
      ability to synthesise PCT of fully differentiated (M0), polarized (M1/M2)
      macrophages and those cultured either in the presence of first trimester gravid
      serum (GS) or pregnancy hormones. We found out that M1 macrophages upregulate PCT
      expression following LPS stimulation compared to M0 and M2. The GS downregulates
      PCT expression in macrophages, skewing them towards an M2-like phenotype. This
      effect seems only partially mediated by the hormonal milieu. Our findings
      strengthen the key role of macrophages in counteracting inflammatory stimuli
      during pregnancy, suggesting PCT as a possible new marker of M1-like macrophages.

PMID- 24733961
TI  - Importins and exportins regulating allergic immune responses.
AB  - Nucleocytoplasmic shuttling of macromolecules is a well-controlled process
      involving importins and exportins. These karyopherins recognize and bind to
      receptor-mediated intracellular signals through specific signal sequences that
      are present on cargo proteins and transport into and out of the nucleus through
      nuclear pore complexes. Nuclear localization signals (NLS) present on cargo
      molecules to be imported while nuclear export signals (NES) on the molecules to
      be exported are recognized by importins and exportins, respectively. The
      classical NLS are found on many transcription factors and molecules that are
      involved in the pathogenesis of allergic diseases. In addition, several immune
      modulators, including corticosteroids and vitamin D, elicit their cellular
      responses by regulating the expression and activity of importin molecules. In
      this review article, we provide a comprehensive list of importin and exportin
      molecules and their specific cargo that shuttled between cytoplasm and the
      nucleus. We also critically review the role and regulation of specific importin
      and exportin involved in the transport of activated transcription factors in
      allergic diseases, the underlying molecular mechanisms, and the potential target
      sites for developing better therapeutic approaches. 

PMID- 24733962
TI  - Cytokines as biomarkers in rheumatoid arthritis.
AB  - RA is a complex disease that develops as a series of events often referred to as
      disease continuum. RA would benefit from novel biomarker development for
      diagnosis where new biomarkers are still needed (even if progresses have been
      made with the inclusion of ACPA into the ACR/EULAR 2010 diagnostic criteria) and
      for prognostic notably in at risk of evolution patients with autoantibody
      positive arthralgia. Risk biomarkers for rapid evolution or cardiovascular
      complications are also highly desirable. Monitoring biomarkers would be useful in
      predicting relapse. Finally, predictive biomarkers for therapy outcome would
      allow tailoring therapy to the individual. Increasing numbers of cytokines have
      been involved in RA pathology. Many have the potential as biomarkers in RA
      especially as their clinical utility is already established in other diseases and
      could be easily transferable to rheumatology. We will review the current
      knowledge's relation to cytokine used as biomarker in RA. However, given the
      complexity and heterogeneous nature of RA, it is unlikely that a single cytokine
      may provide sufficient discrimination; therefore multiple biomarker signatures
      may represent more realistic approach for the future of personalised medicine in
      RA. 

PMID- 24733963
TI  - A role of lipid metabolism during cumulus-oocyte complex maturation: impact of
      lipid modulators to improve embryo production.
AB  - Oocyte intracellular lipids are mainly stored in lipid droplets (LD) providing
      energy for proper growth and development. Lipids are also important signalling
      molecules involved in the regulatory mechanisms of maturation and hence in oocyte
      competence acquisition. Recent studies show that LD are highly dynamic
      organelles. They change their shape, volume, and location within the ooplasm as
      well as their interaction with other organelles during the maturation process.
      The droplets high lipid content has been correlated with impaired oocyte
      developmental competence and low cryosurvival. Yet the underlying mechanisms are
      not fully understood. In particular, the lipid-rich pig oocyte might be an
      excellent model to understand the role of lipids and fatty acid metabolism during
      the mammalian oocyte maturation and their implications on subsequent monospermic
      fertilization and preimplantation embryo development. The possibility of using
      chemical molecules to modulate the lipid content of oocytes and embryos to
      improve cryopreservation as well as its biological effects during development is
      here described. Furthermore, these principles of lipid content modulation may be
      applied not only to germ cells and embryo cryopreservation in livestock
      production but also to biomedical fundamental research. 

PMID- 24733964
TI  - New insight for the diagnosis of gastrointestinal acute graft-versus-host
      disease.
AB  - Allogeneic stem cell transplantation (allo-SCT) is a curative therapy for
      different life-threatening malignant and nonmalignant hematologic disorders.
      Graft-versus-host disease (GVHD) remains a major source of morbidity and
      mortality following allo-SCT, which limits the use of this treatment in a broader
      spectrum of patients. Early diagnostic of GVHD is essential to initiate treatment
      as soon as possible. Unfortunately, the diagnosis of GVHD may be difficult to
      establish, because of the nonspecific nature of the associated symptoms and of
      the numerous differential diagnosis. This is particularly true regarding
      gastrointestinal (GI) acute GVHD. In the recent years many progress has been made
      in medical imaging test and endoscopic techniques. The interest of these
      different techniques in the diagnosis of GI acute GVHD has been evaluated in
      several studies. With this background we review the contributions, limitations,
      and future prospect of these techniques in the diagnosis of GI acute GVHD. 

PMID- 24733965
TI  - The proinflammatory cytokine high-mobility group box-1 mediates retinal
      neuropathy induced by diabetes.
AB  - To test the hypothesis that increased expression of proinflammatory cytokine high
      mobility group box-1 (HMGB1) in epiretinal membranes and vitreous fluid from
      patients with proliferative diabetic retinopathy and in retinas of diabetic rats
      plays a pathogenetic role in mediating diabetes-induced retinal neuropathy.
      Retinas of 1-month diabetic rats and HMGB1 intravitreally injected normal rats
      were studied using Western blot analysis, RT-PCR and glutamate assay. In
      addition, we studied the effect of the HMGB1 inhibitor glycyrrhizin on diabetes
      induced biochemical changes in the retina. Diabetes and intravitreal injection of
      HMGB1 in normal rats induced significant upregulation of HMGB1 protein and mRNA,
      activated extracellular signal-regulated kinase 1 and 2 (ERK1/2), cleaved caspase
      3 and glutamate; and significant downregulation of synaptophysin, tyrosine
      hydroxylase, glutamine synthetase, and glyoxalase 1. Constant glycyrrhizin intake
      from the onset of diabetes did not affect the metabolic status of the diabetic
      rats, but it significantly attenuated diabetes-induced upregulation of HMGB1
      protein and mRNA, activated ERK1/2, cleaved caspase-3, and glutamate. In the
      glycyrrhizin-fed diabetic rats, the decrease in synaptophysin, tyrosine
      hydroxylase, and glyoxalase 1 caused by diabetes was significantly attenuated.
      These findings suggest that early retinal neuropathy of diabetes involves
      upregulated expression of HMGB1 and can be ameliorated by inhibition of HMGB1. 

PMID- 24733966
TI  - Upregulating nonneuronal cholinergic activity decreases TNF release from
      lipopolysaccharide-stimulated RAW264.7 cells.
AB  - Nonneuronal cholinergic system plays a primary role in maintaining homeostasis.
      It has been proved that endogenous neuronal acetylcholine (ACh) could play an
      anti-inflammatory role, and exogenous cholinergic agonists could weaken
      macrophages inflammatory response to lipopolysaccharide (LPS) stimulation through
      activation of alpha7 subunit-containing nicotinic acetylcholine receptor
      (alpha7nAChR). We assumed that nonneuronal cholinergic system existing in
      macrophages could modulate inflammation through autocrine ACh and expressed
      alpha7nAChR on the cells. Therefore, we explored whether LPS continuous
      stimulation could upregulate the nonneuronal cholinergic activity in macrophages
      and whether increasing autocrine ACh could decrease TNF release from the
      macrophages. The results showed that, in RAW264.7 cells incubated with LPS for 20
      hours, the secretion of ACh was significantly decreased at 4 h and then gradually
      increased, accompanied with the enhancement of alpha7nAChR expression level. The
      release of TNF was greatly increased from RAW264.7 cells at 4 h and 8 h exposure
      to LPS; however, it was suppressed at 20 h. Upregulating choline
      acetyltransferase (ChAT) expression through ChAT gene transfection could enhance
      ACh secretion and reduce TNF release from the infected RAW264. 7cells. The
      results indicated that LPS stimulation could modulate the activity of nonneuronal
      cholinergic system of RAW264.7 cells. Enhancing autocrine ACh production could
      attenuate TNF release from RAW264.7 cells.

PMID- 24733967
TI  - Redesigning antidepressant drug discovery.
AB  - Antidepressant drug discovery and development have been put on hold by many
      pharmaceutical companies. The main reason for this is the negative efficacy
      studies with novel specific drugs. Here I argue that the main obstacles are the
      absence of gene tests and biomarkers as an integral part of a diagnostic process.
      Further, too much emphasis has been put on validating drug candidates in animal
      models of psychiatric disorders. A more rapid transfer of drug candidates into
      human research is necessary to overcome current obstacles that prevent the
      discovery of next-generation antidepressants. 

PMID- 24733968
TI  - Pathophysiology of depression and innovative treatments: remodeling glutamatergic
      synaptic connections.
AB  - Despite the complexity and heterogeneity of mood disorders, basic and clinical
      research studies have begun to elucidate the pathophysiology of depression and to
      identify rapid, efficacious antidepressant agents. Stress and depression are
      associated with neuronal atrophy, characterized by loss of synaptic connections
      in key cortical and limbic brain regions implicated in depression. This is
      thought to occur in part via decreased expression and function of growth factors,
      such as brain-derived neurotrophic factor (BDNF), in the prefrontal cortex (PFC)
      and hippocampus. These structural alterations are difficult to reverse with
      typical antidepressants. However, recent studies demonstrate that ketamine, an N
      methyl-D-aspartate (NMDA) receptor antagonist that produces rapid antidepressant
      actions in treatment-resistant depressed patients, rapidly increases spine
      synapses in the PFC and reverses the deficits caused by chronic stress. This is
      thought to occur by disinhibition of glutamate transmission, resulting in a rapid
      but transient burst of glutamate, followed by an increase in BDNF release and
      activation of downstream signaling pathways that stimulate synapse formation.
      Recent work demonstrates that the rapid-acting antidepressant effects of
      scopolamine, a muscarinic receptor antagonist, are also associated with increased
      glutamate transmission and synapse formation. These findings have resulted in
      testing and identification of additional targets and agents that influence
      glutamate transmission and have rapid antidepressant actions in rodent models and
      in clinical trials. Together these studies have created tremendous excitement and
      hope for a new generation of rapid, efficacious antidepressants. 

PMID- 24733969
TI  - Serotonin-related pathways and developmental plasticity: relevance for
      psychiatric disorders.
AB  - Risk for adult psychiatric disorders is partially determined by early-life
      alterations occurring during neural circuit formation and maturation. In this
      perspective, recent data show that the serotonin system regulates key cellular
      processes involved in the construction of cortical circuits. Translational data
      for rodents indicate that early-life serotonin dysregulation leads to a wide
      range of behavioral alterations, ranging from stress-related phenotypes to social
      deficits. Studies in humans have revealed that serotonin-related genetic variants
      interact with early-life stress to regulate stress-induced cortisol
      responsiveness and activate the neural circuits involved in mood and anxiety
      disorders. Emerging data demonstrate that early-life adversity induces epigenetic
      modifications in serotonin-related genes. Finally, recent findings reveal that
      selective serotonin reuptake inhibitors can reinstate juvenile-like forms of
      neural plasticity, thus allowing the erasure of long-lasting fear memories. These
      approaches are providing new insights on the biological mechanisms and clinical
      application of antidepressants. 

PMID- 24733971
TI  - Proteomics, metabolomics, and protein interactomics in the characterization of
      the molecular features of major depressive disorder.
AB  - Omics technologies emerged as complementary strategies to genomics in the attempt
      to understand human illnesses. In general, proteomics technologies emerged
      earlier than those of metabolomics for major depressive disorder (MDD) research,
      but both are driven by the identification of proteins and/or metabolites that can
      delineate a comprehensive characterization of MDD's molecular mechanisms, as well
      as lead to the identification of biomarker candidates of all types-prognosis,
      diagnosis, treatment, and patient stratification. Also, one can explore protein
      and metabolite interactomes in order to pinpoint additional molecules associated
      with the disease that had not been picked up initially. Here, results and
      methodological aspects of MDD research using proteomics, metabolomics, and
      protein interactomics are reviewed, focusing on human samples. 

PMID- 24733972
TI  - Functional neuroimaging studies of the effects of psychotherapy.
AB  - It has been long established that psychological interventions can markedly alter
      patients' thinking patterns, beliefs, attitudes, emotional states, and behaviors.
      Little was known about the neural mechanisms mediating such alterations before
      the advent of functional neuroimaging techniques. Since the turn of the new
      millenium, several functional neuroimaging studies have been conducted to tackle
      this important issue. Some of these studies have explored the neural impact of
      various forms of psychotherapy in individuals with major depressive disorder.
      Other neuroimaging studies have investigated the effects of psychological
      interventions for anxiety disorders. I review these studies in the present
      article, and discuss the putative neural mechanisms of change in psychotherapy.
      The findings of these studies suggest that mental and behavioral changes
      occurring during psychotherapeutic interventions can lead to a normalization of
      functional brain activity at a global level. 

PMID- 24733970
TI  - Emerging role of microRNAs in major depressive disorder: diagnosis and
      therapeutic implications.
AB  - Major depressive disorder (MDD) is a major public health concern. Despite
      tremendous advances, the pathogenic mechanisms associated with MDD are still
      unclear. Moreover, a significant number of MDD subjects do not respond to the
      currently available medication. MicroRNAs (miRNAs) are a class of small noncoding
      RNAs that control gene expression by modulating translation, messenger RNA (mRNA)
      degradation, or stability of mRNA targets. The role of miRNAs in disease
      pathophysiology is emerging rapidly. Recent studies demonstrating the involvement
      of miRNAs in several aspects of neural plasticity, neurogenesis, and stress
      response, and more direct studies in human postmortem brain provide strong
      evidence that miRNAs can not only play a critical role in MDD pathogenesis, but
      can also open up new avenues for the development of therapeutic targets.
      Circulating miRNAs are now being considered as possible biomarkers in disease
      pathogenesis and in monitoring therapeutic responses because of the presence
      and/or release of miRNAs in blood cells as well as in other peripheral tissues.
      In this review, these aspects are discussed in a comprehensive and critical
      manner. 

PMID- 24733973
TI  - Deep brain stimulation in the treatment of depression.
AB  - Major depressive disorder is a worldwide disease with debilitating effects on a
      patient's life. Common treatments include pharmacotherapy, psychotherapy, and
      electroconvulsive therapy. Many patients do not respond to these treatments; this
      has led to the investigation of alternative therapeutic modalities. Deep brain
      stimulation (DBS) is one of these modalities. It was first used with success for
      treating movement disorders and has since been extended to the treatment of
      psychiatric disorders. Although DBS is still an emerging treatment, promising
      efficacy and safety have been demonstrated in preliminary trials in patients with
      treatment-resistant depression (TRD). Further, neuroimaging has played a pivotal
      role in identifying some DBS targets and remains an important tool for evaluating
      the mechanism of action of this novel intervention. Preclinical animal studies
      have broadened knowledge about the possible mechanisms of action of DBS for TRD,
      Given that DBS involves neurosurgery in patients with severe psychiatric
      impairment, ethical questions concerning capacity to consent arise; these issues
      must continue to be carefully considered. 

PMID- 24733974
TI  - Endogenous and exogenous electric fields as modifiers of brain activity: rational
      design of noninvasive brain stimulation with transcranial alternating current
      stimulation.
AB  - Synchronized neuronal activity in the cortex generates weak electric fields that
      are routinely measured in humans and animal models by electroencephalography and
      local field potential recordings. Traditionally, these endogenous electric fields
      have been considered to be an epiphenomenon of brain activity. Recent work has
      demonstrated that active cortical networks are surprisingly susceptible to weak
      perturbations of the membrane voltage of a large number of neurons by electric
      fields. Simultaneously, noninvasive brain stimulation with weak, exogenous
      electric fields (transcranial current stimulation, TCS) has undergone a
      renaissance due to the broad scope of its possible applications in modulating
      brain activity for cognitive enhancement and treatment of brain disorders. This
      review aims to interface the recent developments in the study of both endogenous
      and exogenous electric fields, with a particular focus on rhythmic stimulation
      for the modulation of cortical oscillations. The main goal is to provide a
      starting point for the use of rational design for the development of novel
      mechanism-based TCS therapeutics based on transcranial alternating current
      stimulation, for the treatment of psychiatric illnesses. 

PMID- 24733975
TI  - Neurofeedback and networks of depression.
AB  - Recent advances in imaging technology and in the understanding of neural circuits
      relevant to emotion, motivation, and depression have boosted interest and
      experimental work in neuromodulation for affective disorders. Real-time
      functional magnetic resonance imaging (fMRI) can be used to train patients in the
      self regulation of these circuits, and thus complement existing neurofeedback
      technologies based on electroencephalography (EEG). EEG neurofeedback for
      depression has mainly been based on models of altered hemispheric asymmetry. fMRI
      based neurofeedback (fMRI-NF) can utilize functional localizer scans that allow
      the dynamic adjustment of the target areas or networks for self-regulation
      training to individual patterns of emotion processing. An initial application of
      fMRI-NF in depression has produced promising clinical results, and further
      clinical trials are under way. Challenges lie in the design of appropriate
      control conditions for rigorous clinical trials, and in the transfer of
      neurofeedback protocols from the laboratory to mobile devices to enhance the
      sustainability of any clinical benefits. 

PMID- 24733976
TI  - Henri Laborit and the inhibition of action.
AB  - Henri Laborit was one of the founders of modern neuropsychopharmacology, having
      discovered, or participated in, the discovery of chlorpromazine, gamma-OH,
      clomethiazole, and minaprine. He also put forward a theory regarding the
      necessity of counteracting the negative consequences of defense mechanisms during
      anesthesia or behavioral inhibition. The scope of his work covers
      neurophysiology, pharmacology, psychiatry, and psychosomatics. His independence
      of spirit meant that most of his research was not done within university
      settings. 

PMID- 24733977
TI  - Use of Web and Phone Survey Modes to Gather Data From Adults About Their Young
      Adult Children: An Evaluation Based on a Randomized Design.
AB  - Mode effects on responses to survey items may introduce bias to data collected
      using multiple modes of administration. The present study examines data from 704
      surveys conducted as part of a longitudinal study in which parents and their
      children had been surveyed at multiple prior time points. Parents of 22-year-old
      study participants were randomly assigned to one of two mixed-mode conditions:
      (a) Web mode first followed by the offer of an interviewer-administered telephone
      mode; or (b) telephone mode first followed by the offer of the Web mode.
      Comparison of responses by assigned condition on 12 measures showed one
      statistically significant difference. Analyses that modeled differences by
      completed mode and the interaction between assigned condition and completed mode
      found significant differences on six measures related to completed mode. None of
      the differences indicated that more socially desirable responses were given in
      interviewer-administered surveys.

PMID- 24733978
TI  - Sleep apnea and 20-year follow-up for all-cause mortality, stroke, and cancer
      incidence and mortality in the Busselton Health Study cohort.
AB  - OBJECTIVE: To ascertain whether objectively measured obstructive sleep apnea
      (OSA) independently increases the risk of all cause death, cardiovascular disease
      (CVD), coronary heart disease (CHD), stroke or cancer. DESIGN: Community-based
      cohort. SETTING AND PARTICIPANTS: 400 residents of the Western Australian town of
      Busselton. MEASURES: OSA severity was quantified via the respiratory disturbance
      index (RDI) as measured by a single night recording in November-December 1990
      using the MESAM IV device, along with a range of other risk factors. Follow-up
      for deaths and hospitalizations was ascertained via record linkage to the end of
      2010. RESULTS: We had follow-up data in 397 people and then removed those with a
      previous stroke (n = 4) from the mortality/ CVD/CHD/stroke analyses and those
      with cancer history from the cancer analyses (n = 7). There were 77 deaths, 103
      cardiovascular events (31 strokes, 59 CHD) and 125 incident cases of cancer (39
      cancer fatalities) during 20 years follow-up. In fully adjusted models, moderate
      severe OSA was significantly associated with all-cause mortality (HR = 4.2; 95%
      CI 1.9, 9.2), cancer mortality (3.4; 1.1, 10.2), incident cancer (2.5; 1.2, 5.0),
      and stroke (3.7; 1.2, 11.8), but not significantly with CVD (1.9; 0.75, 4.6) or
      CHD incidence (1.1; 0.24, 4.6). Mild sleep apnea was associated with a halving in
      mortality (0.5; 0.27, 0.99), but no other outcome, after control for leading risk
      factors. CONCLUSIONS: Moderate-to-severe sleep apnea is independently associated
      with a large increased risk of all-cause mortality, incident stroke, and cancer
      incidence and mortality in this community-based sample.

PMID- 24733979
TI  - Emerging from the shadows: a possible link between sleep apnea and cancer.

PMID- 24733980
TI  - Blood pressure improvement with continuous positive airway pressure is
      independent of obstructive sleep apnea severity.
AB  - STUDY OBJECTIVES: We sought to perform a patient-level meta-analysis using the
      individual patient data of the trials identified in our previous study-level meta
      analysis investigating the effect of positive airway pressure (PAP) treatment for
      obstructive sleep apnea (OSA) on blood pressure (BP). DESIGN: Patient-level meta
      analysis. SETTING: N/A. PARTICIPANTS: 968 adult OSA subjects without major
      comorbidities drawn from eight randomized controlled trials. INTERVENTIONS:
      Therapeutic PAP versus non-therapeutic control conditions (sham-PAP, pill placebo
      or standard care) over at least one week. MEASUREMENTS AND RESULTS: The mean
      reductions in BP between PAP and non-therapeutic control arms were -2.27 mm Hg
      (95% CI -4.01 to -0.54) for systolic BP and -1.78 mm Hg (95% CI -2.99 to -0.58)
      for diastolic BP. The presence of uncontrolled hypertension at baseline was
      significantly associated with a reduction in systolic BP of 7.1 mm Hg and
      diastolic BP of 4.3 mm Hg after controlling for OSA severity (apnea-hypopnea
      index, Epworth Sleepiness Scale score, PAP level), patient demographics (age,
      gender, body mass index, use of antihypertensive medication/s), and measures of
      PAP efficacy (PAP adherence and treatment duration). CONCLUSIONS: OSA patients
      with uncontrolled hypertension are likely to gain the largest benefit from PAP in
      terms of a substantial reduction in BP, even after controlling for disease
      severity.

PMID- 24733981
TI  - Is technologist review of raw data necessary after home studies for sleep apnea?
AB  - STUDY OBJECTIVES: As the importance of portable monitors for detection of sleep
      apnea increases, efficient and cost-minimizing methods for data interpretation
      are needed. We sought to compare in stroke patients, for whom portable studies
      often have particular advantages, results from a cardiopulmonary monitoring
      device with and without manual edits by a polysomnographic technologist. METHODS:
      Participants in an ongoing stroke surveillance study in Corpus Christi, Texas,
      underwent sleep apnea assessments with the ApneaLink Plus device within 45 days
      of stroke onset. Recordings were analyzed by the device's software unedited, and
      again after edits were made to the raw data by a registered polysomnographic
      technologist. Sensitivity and specificity were calculated, with the edited data
      as the reference standard. Sleep apnea was defined by 3 different apnea-hypopnea
      index (AHI) thresholds: >= 5, >= 10, and >= 15. RESULTS: Among 327 subjects, 54%
      were male, 59% were Hispanic, and the median age was 65 years (interquartile
      range: 57, 77). The median AHI for the unedited data was 9 (4, 22), and for the
      edited data was 13 (6, 27) (p < 0.01). Specificity was above 98% for each AHI
      cutoff, while sensitivity was 81% to 82%. For each cutoff threshold, the edited
      data yielded a higher proportion of positive sleep apnea screens (p < 0.01) by
      approximately 10% in each group. CONCLUSIONS: For stroke patients assessed with a
      cardiopulmonary monitoring device, manual editing by a technologist appears
      likely to improve sensitivity, whereas specificity of unedited data is already
      excellent.

PMID- 24733982
TI  - Effect of addition of chin strap on PAP compliance, nightly duration of use, and
      other factors.
AB  - STUDY OBJECTIVES: A chinstrap is potentially useful to reduce unintentional air
      leak by preventing mouth opening during PAP treatment. This study examines
      whether the addition of a chinstrap to PAP therapy has any effect on adherence,
      nightly duration of use, air leak, and residual AHI. METHODS: This was a
      retrospective study performed at an AASM-accredited VAMC sleep center. Clinical
      sleep data of veterans (n = 124) prescribed PAP therapy for sleep apnea was
      evaluated, and the effect of chinstrap use vs non-use on the above parameters was
      assessed. RESULTS: Chinstrap users had significantly greater PAP adherence,
      longer nightly duration of PAP use, lower residual AHI and lower leak compared to
      chinstrap non-users at first follow up visit. CONCLUSIONS: The addition of a chin
      strap to PAP therapy is a simple and inexpensive method of increasing PAP
      adherence.

PMID- 24733983
TI  - Nasopharyngeal tube: a simple and effective tool to screen patients indicated for
      glossopharyngeal surgery.
AB  - STUDY OBJECTIVES: The aim of this prospective controlled study was to explore the
      diagnostic value of repeated polysomnography (PSG) post-nasopharyngeal tube
      insertion in the setting of glossopharyngeal obstruction in obstructive sleep
      apnea hypopnea syndrome (OSAHS). METHODS: Patients were eligible for this study
      if they were diagnosed as OSAHS by the first PSG and presented with moderate to
      severe OSAHS by repeated PSG scanning post-nasopharyngeal tube insertion (NPT
      PSG). Fifty-nine patients were enrolled into this study and assigned to received
      either modified uvulopalatopharyngoplasty (H-UPPP; n = 25) or H-UPPP in
      combination with glossopharyngeal surgery (n = 34). RESULTS: General data and PSG
      data were collected prior to and following nasopharyngeal tube insertion and were
      found not to be significantly different. However, both the PSG and Epworth
      sleepiness scale (ESS) were significantly superior in the combination group
      compared to the UPPP alone group post-surgery. The success rates of surgery were
      82.3% and 40.0%, respectively. CONCLUSION: Patients with moderate to severe OSAHS
      post-nasopharyngeal tube insertion generally have glossopharyngeal obstruction.
      Glossopharyngeal surgery can significantly improve surgical outcome in the
      setting of OSAHS.

PMID- 24733984
TI  - High hypopnea/apnea ratio (HAR) in extreme obesity.
AB  - STUDY OBJECTIVES: The study was performed to evaluate the hypothesis that the
      extremely obese manifest sleep disordered breathing with a preponderance of
      hypopneas and relative paucity of obstructive apneas. METHODS: Retrospective
      review of 90 adults with obstructive sleep apnea-hypopnea syndrome (OSAHS)
      matched for age and gender, comparing two groups, Group A: body mass index (BMI)
      < 35, Group B: BMI >= 45. EXCLUSION CRITERIA: age < 18 years, pregnancy, >= 5
      central apneas/hour, BMI >= 35 < 45. PRIMARY OUTCOME MEASURE: Hypopnea/apnea
      ratio (HAR); secondary measures: obstructive apnea-hypopnea index (AHI),
      obstructive and central apnea indices, hypopnea index (HI), oxygen saturation
      (SpO2) nadir, end-tidal carbon dioxide tension (PetCO2), and presence of obesity
      hypoventilation syndrome (OHS). STATISTICAL METHODS: t-test for independent
      samples; Mann-Whitney, linear regression with natural log transformation, and
      Kruskal-Wallis chi(2). Descriptive statistics were expressed as interquartile
      range, median and mean +/- standard deviation, p < 0.05 considered significant.
      RESULTS: Group A (n = 45): age = 50.6 +/- 11.5 years, BMI = 28.9 +/- 4 kg/m(2);
      Group B (n = 45): age = 47.4 +/- 12.7 years, BMI = 54.5 +/- 8 kg/m(2). HAR was
      significantly higher in Group B (38.8 +/- 50.7) than Group A (10.6 +/- 16.5), p =
      0.0006, as was HI (28.7 +/- 28.6 in B vs 12.6 +/- 8.4 in A, p = 0.0005) and AHI
      (35.5 +/- 33.8 vs 22 +/- 23, p = 0.03), but not apnea index. HAR was
      significantly higher in Group B regardless of race, gender, or presence of OHS.
      The BMI was the only significant predictor of HAR (adjusted r(2) = 0.138; p =
      0.002) in a linear regression model with natural log transformation of the HAR
      performed for age, gender, race, BMI, and PetCO2. CONCLUSION: Extremely obese
      patients manifest OSAHS with a preponderance of hypopneas.

PMID- 24733985
TI  - Comparison of BMI, AHI, and apolipoprotein E epsilon4 (APOE-epsilon4) alleles
      among sleep apnea patients with different skeletal classifications.
AB  - STUDY OBJECTIVES: This case-control study investigated whether variations within
      the APOE-epsilon gene were associated with having a convex facial profile
      (skeletal Class II) compared to exhibiting a straight or concave facial profile
      (Class I or Class III) among patients with obstructive sleep apnea (OSA).
      Associations between the apnea-hypopnea index (AHI) and body mass index (BMI)
      scores for these OSA patients were also examined in the context of facial
      profile. METHOD: OSA patients with an AHI >= 15 were recruited from a sleep
      clinic and classified by facial and dental occlusal relationships based on a
      profile facial analysis, lateral photographs, and dental examination. Saliva was
      collected as a source of DNA. The APOE-epsilon1-4 allele-defining single
      nucleotide polymorphisms (SNPs) rs429358 and rs7412 were genotyped. A chi(2)
      analysis was used to assess Hardy-Weinberg equilibrium and for association
      analysis (significance at p < 0.05). ANOVA and Fisher exact test were also used.
      RESULT: Seventy-six Caucasian OSA patients participated in the study-25 Class II
      cases and 51 non-Class II cases. There was no association of the APOE-epsilon4
      allele with facial profile among these OSA patients. Class II OSA patients had
      significantly lower BMIs (30.7 +/- 5.78) than Class I (37.3 +/- 6.14) or Class
      III (37.8 +/- 6.17) patients (p < 0.001), although there was no statistical
      difference in AHI for Class II patients compared with other groups. CONCLUSION:
      OSA patients with Class II convex profile were more likely to have a lower BMI
      than those in other skeletal groups. In fact 20% of them were not obese,
      suggesting that a Class II convex profile may influence or be associated with OSA
      development independent of BMI.

PMID- 24733986
TI  - Prader Willi syndrome and obstructive sleep apnea: co-occurrence in the pediatric
      population.
AB  - BACKGROUND: A high prevalence of obstructive sleep apnea (OSA) occurs in children
      with Prader-Willi syndrome (PWS). Yet, due in part to the relatively small
      samples previously used, the prevalence of OSA has varied greatly across studies.
      It is also unclear if factors such as age, gender, body mass index (BMI), or type
      of genetic imprinting are associated with increased risk for OSA among children
      with PWS. OBJECTIVES: To evaluate the (a) prevalence of OSA, as well as
      narcolepsy, in pediatric populations diagnosed with PWS; (b) effects of age,
      gender, body mass index, and genetic imprinting on OSA severity; and (c) efficacy
      of adenotonsillectomy (AT) for decreasing OSA severity in this population.
      METHODS: All studies assessing OSA among children with PWS through August 2013
      were identified using the PubMed/Medline, Psych Info, Cochrane library, and
      Google Scholar data bases. RESULTS: Fourteen studies of children diagnosed with
      PWS and who were assessed for OSA using polysomnography (PSG) met inclusion
      criteria (n = 224 children). The prevalence of OSA across studies was 79.91% (n =
      179/224). Among youths with OSA, 53.07% had mild OSA, 22.35% moderate OSA, and
      24.58% severe OSA. Narcolepsy was found to occur in 35.71% of children with PWS.
      Adenotonsillectomy was associated with improvement in OSA for most children with
      PWS. However, residual OSA was present in the majority of cases post-surgery.
      CONCLUSION: This study confirms the high prevalence of OSA and narcolepsy among
      children with PWS. Screening for OSA and narcolepsy among children with PWS is
      recommended. In addition, while adenotonsillectomy was effective in reducing OSA
      for some children, alternative treatments may need to be considered, given the
      only moderate response rate.

PMID- 24733988
TI  - Sleep problems and sleep disorders in pediatric primary care: treatment
      recommendations, persistence, and health care utilization.
AB  - STUDY OBJECTIVE: This study examined documented treatment recommendations
      provided for sleep disorders and sleep problems in pediatric primary care, the
      persistence of sleep problems and sleep disorders in children and adolescents,
      and the relationship between sleep issues and health care utilization. METHODS:
      In-depth chart review of pediatric primary care patient visits (n = 750 patients)
      from 2007 through 2010. RESULTS: Only 26 children (5.2% of those with a sleep
      disorder/ problem) received a treatment recommendation, with half of these
      recommendations behavioral in nature. Sleep disorders and sleep problems were
      highly persistent across time for up to a third of children. Children with sleep
      disorders had significantly more sick visits/calls (mean = 8.84, 95% CI 7.77
      9.90) than children without a sleep disorder (mean = 6.34, 95% CI 5.56-7.12).
      CONCLUSIONS: Very few children or adolescents were found to have documented
      treatment recommendations or referrals for diagnosed sleep disorders or sleep
      problems. In addition, given that sleep disorders and sleep problems are highly
      persistent, as well as result in more sick visits/calls, it is important that
      pediatric primary care providers screen for and identify these issues across
      development. Furthermore, it is essential to provide health care providers with
      more education and support on sleep disorders and sleep problems in pediatric
      primary care.

PMID- 24733987
TI  - High prevalence of sleep disorders and associated comorbidities in a community
      sample of children with Down syndrome.
AB  - STUDY OBJECTIVES: Down syndrome (DS) is a neurodevelopmental disorder
      characterized by multiple comorbidities. Sleep disorders are common among
      children with DS and can cause significant distress for families. However,
      research is limited describing sleep problems and correlates in large population
      based samples. Accordingly, we aimed to describe sleep behavior among children
      with DS and its relationship with medical conditions in this population. METHODS:
      We conducted a population-based, cross-sectional study (2009-2011) of sleep
      disturbances in children and adolescents with DS 7 to 17 years of age (N = 107).
      We assessed sleep problems using caregiver report on two validated screening
      tools: the Childhood Sleep Habits Questionnaire (CSHQ) and the Pediatric Sleep
      Questionnaire (PSQ). The prevalence of sleep problems was compared in children
      with and without important comorbidities using modified Poisson regression with
      robust standard errors. RESULTS: 65% of children screened positive on the CSHQ
      for significant sleep problems in the past month, but their parents often did not
      report sleeping difficulties in their children. On the PSQ, 46% screened positive
      for sleep related breathing problems and 21% screened positive for sleep related
      movement disorders. Children with asthma, autism, and a history of enlarged
      adenoids and tonsils had more current sleep problems than children without these
      comorbidities. CONCLUSIONS: Our findings suggest that sleep problems may be an
      important but under-recognized problem in children with DS. Sleep problems appear
      to be correlated with prevalent comorbidities, which may provide guidance to
      augment current practice guidelines to evaluate sleep problems in this
      population.

PMID- 24733990
TI  - Change in quality of life after brief behavioral therapy for insomnia in
      concurrent depression: analysis of the effects of a randomized controlled trial.
AB  - STUDY OBJECTIVES: The efficacy of cognitive behavioral therapy for insomnia (CBT
      I) has been suggested for insomnia concomitant with depression, but its impact on
      quality of life (QoL) has not been adequately evaluated. The study aimed to
      determine which aspects of QoL could be affected by CBT-I and how any changes in
      QoL were mediated by changes in insomnia and depression. METHODS: We conducted a
      4-week randomized controlled trial with 4-week follow-up in outpatient clinics in
      Japan. Thirty-seven patients with DSM-IV diagnosis of major depressive disorder
      concomitant with chronic insomnia were randomly assigned to the treatment-as
      usual (TAU) alone arm or the TAU with brief behavioral therapy for insomnia (TAU
      plus psychotherapy) arm using modified CBT-I consisting of 4 weekly individual
      sessions. We evaluated QoL using norm-based scoring of the Short Form-36 at
      baseline and at 8 weeks. We also examined associations between QoL subscales and
      remission in insomnia or depression while controlling for baseline scores of the
      entire sample. RESULTS: We tested group effects while controlling for baseline
      scores. TAU plus psychotherapy resulted in significantly better scores on
      physical functioning (p = 0.006), social functioning (p = 0.002), and mental
      health (p = 0.041) subscales than TAU alone at 8 weeks. Patients with either
      remitted insomnia or depression showed higher QoL scores than non-remitted
      patients; scores approximated those within the normal range. CONCLUSIONS: For
      patients with insomnia in depression, adding CBT-I to TAU can produce substantive
      benefits in some aspects of QoL. TRIAL REGISTRATION: ClinicalTrials.gov
      Identifier: NCT00610259, http://www.clinicaltrials.gov/.

PMID- 24733989
TI  - The link between sleep disturbance and depression among Mexican Americans: a
      Project FRONTIER study.
AB  - OBJECTIVE: To examine the link between disturbed sleep and depression scores in
      Mexican Americans and non-Hispanic Whites. METHODS: Data were analyzed for 566
      participants (45% Mexican Americans) who were part of a rural healthcare study,
      Project FRONTIER. Mean age was 55.5 years for Mexican Americans (70% female) and
      65.6 years for non-Hispanic Whites (69% female). Self-reported sleep disturbance
      was entered as the predictor, GDS-30 total and factor scores as the outcome
      variables, and age, sex, education, BMI, and medical diagnoses (hyperlipidemia,
      diabetes mellitus, and hypertension) entered as covariates. RESULTS: Mexican
      Americans reported higher rates of sleep disturbances (25%) than non-Hispanic
      whites (17%). Sleep disturbances were significantly associated with GDS-30 total
      scores and the factors Dysphoria and Cognitive Impairment in both Mexican
      Americans and non-Hispanic whites. CONCLUSIONS: In this study, Mexican Americans
      reported higher rates of sleep disturbances than non-Hispanic whites. Disturbed
      sleep was positively associated with depression and the factor scores for
      Dysphoria and Cognitive Impairment in both groups. Given the paucity of research
      on sleep disorders in Mexican Americans, identifying what sleep disorders are
      present and the impact treating these sleep disorders have on depression warrant
      further investigation.

PMID- 24733991
TI  - CPAP therapy reverses weakness of myasthenia gravis: role of obstructive sleep
      apnea in paradoxical weakness of myasthenia gravis.
AB  - Fatigability after exercise and restoration of strength by rest are clinical
      hallmarks of myasthenia gravis (MG). These unique features are originated from a
      reduced safety factor, which is related to a defect of acetylcholine receptor,
      and post-exercise exhaustion of neuromuscular junction transmission. Therefore,
      most patients with MG feel recharged muscle strength and show normal muscle power
      after nocturnal sleep. As such, worsening of MG symptoms during nighttime is
      usual. However, in very rare cases, some patients with MG complain fatigability
      and weakness in the morning, so called "paradoxical weakness (PW)." We report two
      MG patients with typical PW, diagnosed with OSA by polysomnography. CPAP therapy
      successfully improved their morning symptoms and quality of life. So far, the
      detailed mechanism of PW in MG is unknown; however, our report highlights the
      possible role of sleep disorders in developing a PW in MG and the therapeutic
      target for life quality of MG.

PMID- 24733992
TI  - Sleep-wake pattern following gunshot suprachiasmatic damage.
AB  - BACKGROUND: The suprachiasmatic nucleus (SCN) plays a critical role in
      maintaining melatonin and sleep-wake cycles. METHODS/PATIENT: We report a case of
      38-year-old woman who, after gunshot wound to the right temple, developed a sleep
      complaint of multiple nocturnal awakenings and several naps throughout the day.
      RESULTS: Computerized tomography and magnetic resonance imaging revealed
      bilateral optic nerve and optic chiasm damage. Diagnostic polysomnography and
      actigraphy revealed an irregular sleep wake rhythm. CONCLUSIONS: We speculate
      concurrent damage of the SCN and optic nerves bilaterally resulted in the
      posttraumatic irregular sleep-wake rhythm.

PMID- 24733994
TI  - Nocturnal arousals in a middle-aged woman.

PMID- 24733993
TI  - The American Academy of Sleep Medicine Inter-scorer Reliability program:
      respiratory events.
AB  - STUDY OBJECTIVES: The American Academy of Sleep Medicine (AASM) Inter-scorer
      Reliability program provides a unique opportunity to compare a large number of
      scorers with varied levels of experience to determine agreement in the scoring of
      respiratory events. The objective of this paper is to examine areas of
      disagreement to inform future revisions of the AASM Manual for the Scoring of
      Sleep and Associated Events. METHODS: The sample included 15 monthly records, 200
      epochs each. The number of scorers increased steadily during the period of data
      collection, reaching more than 3,600 scorers by the final record. Scorers were
      asked to identify whether an obstructive, mixed, or central apnea; a hypopnea; or
      no event was seen in each of the 200 epochs. The "correct" respiratory event
      score was defined as the score endorsed by the most scorers. Percentage agreement
      with the majority score was determined for each epoch and the mean agreement
      determined. RESULTS: The overall agreement for scoring of respiratory events was
      93.9% (kappa = 0.92). There was very high agreement on epochs without respiratory
      events (97.4%), and the majority score for most of the epochs (87.8%) was no
      event. For the 364 epochs scored as having a respiratory event, overall agreement
      that some type of respiratory event occurred was 88.4% (kappa = 0.77). The
      agreement for epochs scored as obstructive apnea by the majority was 77.1% (kappa
      = 0.71), and the most common disagreement was hypopnea rather than obstructive
      apnea (14.4%). The agreement for hypopnea was 65.4% (kappa = 0.57), with 16.4%
      scoring no event and 14.8% scoring obstructive apnea. The agreement for central
      apnea was 52.4% (kappa = 0.41). A single epoch was scored as a mixed apnea by a
      plurality of scorers. CONCLUSIONS: The study demonstrated excellent agreement
      among a large sample of scorers for epochs with no respiratory events. Agreement
      for some type of event was good, but disagreements in scoring of apnea vs.
      hypopnea and type of apnea were common. A limitation of the analysis is that most
      of the records had normal breathing. A review of controversial events yielded no
      consistent bias that might be resolved by a change of scoring rules.

PMID- 24733995
TI  - Further experience using clarithromycin in patients with Kleine-Levin syndrome.

PMID- 24733996
TI  - (E)3-2-(1-(2,4-Dihydroxyphenyl)ethyldeneamino)phenyl)-2-methylquinazoline-4(3H)
      one Schiff Base and Its Metal Complexes: A New Drug of Choice against Methicillin
      Resistant Staphylococcus aureus.
AB  - The 3-(2-aminophenyl) quinazolin-2-methyl-4(3H)-one and 2,4-dihydroxyacetophenone
      undergo condensation to afford (E)3-2-(1-(2,4
      dihydroxyphenyl)ethyldeneamino)phenyl)-2-methylquinazoline-4(3H)-one Schiff base
      (DHPEAPMQ). The newly synthesized Schiff base (DHPEAPMQ) and its metal complexes
      were evaluated for their antimicrobial activity against methicillin-resistant
      Staphylococcus aureus isolated from the Gulbarga region in India. The Cu(II),
      Ni(II), and Zn(II) complexes of Schiff base (DHPEAPMQ) showed good antimicrobial
      activity. So, this could be a new drug of choice. 

PMID- 24733997
TI  - Social isolation disrupts hippocampal neurogenesis in young non-human primates.
AB  - Social relationships are crucial for the development and maintenance of normal
      behavior in non-human primates. Animals that are raised in isolation develop
      abnormal patterns of behavior that persist even when they are later reunited with
      their parents. In rodents, social isolation is a stressful event and is
      associated with a decrease in hippocampal neurogenesis but considerably less is
      known about the effects of social isolation in non-human primates during the
      transition from adolescence to adulthood. To investigate how social isolation
      affects young marmosets, these were isolated from other members of the colony for
      1 or 3 weeks and evaluated for alterations in their behavior and hippocampal cell
      proliferation. We found that anxiety-related behaviors like scent-marking and
      locomotor activity increased after social isolation when compared to baseline
      levels. In agreement, grooming-an indicative of attenuation of tension-was
      reduced among isolated marmosets. These results were consistent with increased
      cortisol levels after 1 and 3 weeks of isolation. After social isolation (1 or 3
      weeks), reduced proliferation of neural cells in the subgranular zone of dentate
      granule cell layer was identified and a smaller proportion of BrdU-positive cells
      underwent neuronal fate (doublecortin labeling). Our data is consistent with the
      notion that social deprivation during the transition from adolescence to
      adulthood leads to stress and produces anxiety-like behaviors that in turn might
      affect neurogenesis and contribute to the deleterious consequences of prolonged
      stressful conditions. 

PMID- 24733998
TI  - Neural evidence for description dependent reward processing in the framing
      effect.
AB  - Human decision making can be influenced by emotionally valenced contexts, known
      as the framing effect. We used event-related brain potentials to investigate how
      framing influences the encoding of reward. We found that the feedback related
      negativity (FRN), which indexes the "worse than expected" negative prediction
      error in the anterior cingulate cortex (ACC), was more negative for the negative
      frame than for the positive frame in the win domain. Consistent with previous
      findings that the FRN is not sensitive to "better than expected" positive
      prediction error, the FRN did not differentiate the positive and negative frame
      in the loss domain. Our results provide neural evidence that the description
      invariance principle which states that reward representation and decision making
      are not influenced by how options are presented is violated in the framing
      effect. 

PMID- 24733999
TI  - CYFIP family proteins between autism and intellectual disability: links with
      Fragile X syndrome.
AB  - Intellectual disability (ID) and autism spectrum disorders (ASDs) have in common
      alterations in some brain circuits and brain abnormalities, such as synaptic
      transmission and dendritic spines morphology. Recent studies have indicated a
      differential expression for specific categories of genes as a cause for both
      types of disease, while an increasing number of genes is recognized to produce
      both disorders. An example is the Fragile X mental retardation gene 1 (FMR1),
      whose silencing causes the Fragile X syndrome, the most common form of ID and
      autism, also characterized by physical hallmarks. Fragile X mental retardation
      protein (FMRP), the protein encoded by FMR1, is an RNA-binding protein with an
      important role in translational control. Among the interactors of FMRP, CYFIP1/2
      (cytoplasmic FMRP interacting protein) proteins are good candidates for ID and
      autism, on the bases of their genetic implication and functional properties, even
      if the precise functional significance of the CYFIP/FMRP interaction is not
      understood yet. CYFIP1 and CYFIP2 represent a link between Rac1, the WAVE (WAS
      protein family member) complex and FMRP, favoring the cross talk between actin
      polymerization and translational control. 

PMID- 24734000
TI  - Firing clamp: a novel method for single-trial estimation of excitatory and
      inhibitory synaptic neuronal conductances.
AB  - Understanding non-stationary neuronal activity as seen in vivo requires
      estimation of both excitatory and inhibitory synaptic conductances from a single
      trial of recording. For this purpose, we propose a new intracellular recording
      method, called "firing clamp." Synaptic conductances are estimated from the
      characteristics of artificially evoked probe spikes, namely the spike amplitude
      and the mean subthreshold potential, which are sensitive to both excitatory and
      inhibitory synaptic input signals. The probe spikes, timed at a fixed rate, are
      evoked in the dynamic-clamp mode by injected meander-like current steps, with the
      step duration depending on neuronal membrane voltage. We test the method with
      perforated-patch recordings from isolated cells stimulated by external
      application or synaptic release of transmitter, and validate the method with
      simulations of a biophysically-detailed neuron model. The results are compared
      with the conductance estimates based on conventional current-clamp recordings. 

PMID- 24734002
TI  - Activation of MU-opioid receptors inhibits calcium-currents in the vestibular
      afferent neurons of the rat through a cAMP dependent mechanism.
AB  - Opioid receptors are expressed in the vestibular endorgans (afferent neurons and
      hair cells) and are activated by the efferent system, which modulates the
      discharge of action potentials in vestibular afferent neurons (VANs). In mammals,
      VANs mainly express the MU opioid-receptor, but the function of this receptors
      activation and the cellular mechanisms by which they exert their actions in these
      neurons are poorly studied. To determine the actions of MU opioid receptor (MOR)
      and cell signaling mechanisms in VANs, we made perforated patch-clamp recordings
      of VANs that were obtained from postnatal days 7 to 10 (P7-10) rats and then
      maintained in primary culture. The MOR agonist [D-Ala(2), N-Me-Phe(4), Gly(5)-ol]
      enkephalin (DAMGO) inhibited the total voltage-gated outward current; this effect
      was prevented by the perfusion of a Ca(2+)-free extracellular solution. We then
      studied the voltage-gated calcium current (Ica) and found that DAMGO Met
      enkephalin or endomorphin-1 inhibited the ICa in a dose-response fashion. The
      effects of DAMGO were prevented by the MOR antagonist (CTAP) or by pertussis
      toxin (PTX). The use of specific calcium channel blockers showed that MOR
      activation inhibited T-, L- and N-type ICa. The use of various enzyme activators
      and inhibitors and of cAMP analogs allowed us to demonstrate that the MOR acts
      through a cAMP dependent signaling mechanism. In current clamp experiments, MOR
      activation increased the duration and decreased the amplitude of the action
      potentials and modulated the discharge produced by current injection. Pre
      incubation with PTX occluded MOR activation effect. We conclude that MOR
      activation inhibits the T-, L- and N-type ICa through activation of a Galphai/o
      protein that involves a decrease in AC-cAMP-PKA activity. The modulation of ICa
      may have an impact on the synaptic integration, excitability, and
      neurotransmitter release from VANs. 

PMID- 24734001
TI  - Roles of taurine-mediated tonic GABAA receptor activation in the radial migration
      of neurons in the fetal mouse cerebral cortex.
AB  - gamma-Aminobutyric acid (GABA) depolarizes embryonic cerebrocortical neurons and
      continuous activation of the GABAA receptor (GABAAR) contributes to their tonic
      depolarization. Although multiple reports have demonstrated a role of GABAAR
      activation in neocortical development, including in migration, most of these
      studies have used pharmacological blockers. Herein, we performed in utero
      electroporation in GABA synthesis-lacking homozygous GAD67-GFP knock-in mice
      (GAD67(GFP/GFP)) to label neurons born in the ventricular zone. Three days after
      electroporation, there were no differences in the distribution of labeled cells
      between the genotypes. The dose-response properties of labeled cells to GABA were
      equivalent among genotypes. However, continuous blockade of GABAAR with the
      GABAAR antagonist SR95531 accelerated radial migration. This effect of GABAAR
      blockade in GAD67(GFP/GFP) mice suggested a role for alternative endogenous
      GABAAR agonists. Thus, we tested the role of taurine, which is derived from
      maternal blood but is abundant in the fetal brain. The taurine-evoked currents in
      labeled cells were mediated by GABAAR. Taurine uptake was blocked by a taurine
      transporter inhibitor, 2-(guanidino)ethanesulfonic acid (GES), and taurine
      release was blocked by a volume-sensitive anion channel blocker, 4-(2-butyl-6,7
      dichlor-2-cyclopentylindan-1-on-5-yl) oxobutyric acid, as examined through high
      performance liquid chromatography. GES increased the extracellular taurine
      concentration and induced an inward shift of the holding current, which was
      reversed by SR95531. In a taurine-deficient mouse model, the GABAAR-mediated
      tonic currents were greatly reduced, and radial migration was accelerated. As the
      tonic currents were equivalent among the genotypes of GAD67-GFP knock-in mice,
      taurine, rather than GABA, might play a major role as an endogenous agonist of
      embryonic tonic GABAAR conductance, regulating the radial migration of neurons in
      the developing neocortex. 

PMID- 24734003
TI  - Modulating excitation through plasticity at inhibitory synapses.
AB  - Learning is believed to depend on lasting changes in synaptic efficacy such as
      long-term potentiation and long-term depression. As a result, a profusion of
      studies has tried to elucidate the mechanisms underlying these forms of
      plasticity. Traditionally, experience-dependent changes at excitatory synapses
      were assumed to underlie learning and memory formation. However, with the
      relatively more recent investigation of inhibitory transmission, it had become
      evident that inhibitory synapses are not only plastic, but also provide an
      additional way to modulate excitatory transmission and the induction of
      plasticity at excitatory synapses. Thanks to recent technological advances,
      progress has been made in understanding synaptic transmission and plasticity from
      particular interneuron subtypes. In this review article, we will describe various
      forms of synaptic plasticity that have been ascribed to two fairly well
      characterized populations of interneurons in the hippocampus, those expressing
      cholecystokinin (CCK) and parvalbumin (PV). We will discuss the resulting changes
      in the strength and plasticity of excitatory transmission that occur in the local
      circuit as a result of the modulation of inhibitory transmission. We will focus
      on the hippocampus because this region has a relatively well-understood
      circuitry, numerous forms of activity-dependent plasticity and a multitude of
      identified interneuron subclasses. 

PMID- 24734004
TI  - Extracellular Vesicles in Multiple Sclerosis: What are They Telling Us?
AB  - Extracellular vesicles (EVs) are membrane-bound particles secreted by almost all
      cell types. They are classified depending on their biogenesis and size into
      exosomes and microvesicles or according to their cell origin. EVs play a role in
      cell-to-cell communication, including contact-free cell synapsis, carrying active
      membrane proteins, lipids, and genetic material both inside the particle and on
      their surface. They have been related to several physiological and pathological
      conditions. In particular, increasing concentrations of EVs have been found in
      many autoimmune diseases including multiple sclerosis (MS). MS is a central
      nervous system (CNS) demyelinating disease characterized by relapsing of symptoms
      followed by periods of remission. Close interaction between endothelial cells,
      leukocytes, monocytes, and cells from CNS is crucial for the development of MS.
      This review summarizes the pathological role of EVs in MS and the relationship of
      EVs with clinical characteristics, therapy, and biomarkers of the disease. 

PMID- 24734005
TI  - Nicotinic modulation of cortical circuits.
AB  - The ascending cholinergic neuromodulatory system sends projections throughout
      cortex and has been shown to play an important role in a number of cognitive
      functions including arousal, working memory, and attention. However, despite a
      wealth of behavioral and anatomical data, understanding how cholinergic synapses
      modulate cortical function has been limited by the inability to selectively
      activate cholinergic axons. Now, with the development of optogenetic tools and
      cell-type specific Cre-driver mouse lines, it has become possible to stimulate
      cholinergic axons from the basal forebrain (BF) and probe cholinergic synapses in
      the cortex for the first time. Here we review recent work studying the cell-type
      specificity of nicotinic signaling in the cortex, synaptic mechanisms mediating
      cholinergic transmission, and the potential functional role of nicotinic
      modulation. 

PMID- 24734007
TI  - The claustrum of the bottlenose dolphin Tursiops truncatus (Montagu 1821).
AB  - The mammalian claustrum is involved in processing sensory information from the
      environment. The claustrum is reciprocally connected to the visual cortex and
      these projections, at least in carnivores, display a clear retinotopic
      distribution. The visual cortex of dolphins occupies a position strikingly
      different from that of land mammals. Whether the reshaping of the functional
      areas of the cortex of cetaceans involves also modifications of the claustral
      projections remains hitherto unanswered. The present topographic and
      immunohistochemical study is based on the brains of eight bottlenose dolphins and
      a wide array of antisera against: calcium-binding proteins (CBPs) parvalbumin
      (PV), calretinin (CR), and calbindin (CB); somatostatin (SOM); neuropeptide Y
      (NPY); and the potential claustral marker Gng2. Our observations confirmed the
      general topography of the mammalian claustrum also in the bottlenose dolphin,
      although (a) the reduction of the piriform lobe modifies the ventral
      relationships of the claustrum with the cortex, and (b) the rotation of the
      telencephalon along the transverse axis, accompanied by the reduction of the
      antero-posterior length of the brain, apparently moves the claustrum more
      rostrally. We observed a strong presence of CR-immunoreactive (-ir) neurons and
      fibers, a diffuse but weak expression of CB-ir elements and virtually no PV
      immunostaining. This latter finding agrees with studies that report that PV-ir
      elements are rare in the visual cortex of the same species. NPY- and somatostatin
      containing neurons were evident, while the potential claustral markers Gng2 was
      not identified in the sections, but no explanation for its absence is currently
      available. Although no data are available on the projections to and from the
      claustrum in cetaceans, our results suggest that its neurochemical organization
      is compatible with the presence of noteworthy cortical inputs and outputs and a
      persistent role in the general processing of the relative information. 

PMID- 24734006
TI  - Purkinje cell stripes and long-term depression at the parallel fiber-Purkinje
      cell synapse.
AB  - The cerebellar cortex comprises a stereotyped array of transverse zones and
      parasagittal stripes, built around multiple Purkinje cell subtypes, which is
      highly conserved across birds and mammals. This architecture is revealed in the
      restricted expression patterns of numerous molecules, in the terminal fields of
      the afferent projections, in the distribution of interneurons, and in the
      functional organization. This review provides an overview of cerebellar
      architecture with an emphasis on attempts to relate molecular architecture to the
      expression of long-term depression (LTD) at the parallel fiber-Purkinje cell (pf
      PC) synapse. 

PMID- 24734008
TI  - Recovering stimulus locations using populations of eye-position modulated neurons
      in dorsal and ventral visual streams of non-human primates.
AB  - We recorded visual responses while monkeys fixated the same target at different
      gaze angles, both dorsally (lateral intraparietal cortex, LIP) and ventrally
      (anterior inferotemporal cortex, AIT). While eye-position modulations occurred in
      both areas, they were both more frequent and stronger in LIP neurons. We used an
      intrinsic population decoding technique, multidimensional scaling (MDS), to
      recover eye positions, equivalent to recovering fixated target locations. We
      report that eye-position based visual space in LIP was more accurate (i.e.,
      metric). Nevertheless, the AIT spatial representation remained largely
      topologically correct, perhaps indicative of a categorical spatial representation
      (i.e., a qualitative description such as "left of" or "above" as opposed to a
      quantitative, metrically precise description). Additionally, we developed a
      simple neural model of eye position signals and illustrate that differences in
      single cell characteristics can influence the ability to recover target position
      in a population of cells. We demonstrate for the first time that the ventral
      stream contains sufficient information for constructing an eye-position based
      spatial representation. Furthermore we demonstrate, in dorsal and ventral streams
      as well as modeling, that target locations can be extracted directly from eye
      position signals in cortical visual responses without computing coordinate
      transforms of visual space. 

PMID- 24734009
TI  - Touch increases autonomic coupling between romantic partners.
AB  - Interpersonal touch is of paramount importance in human social bonding and close
      relationships, allowing a unique channel for affect communication. So far the
      effect of touch on human physiology has been studied at an individual level. The
      present study aims at extending the study of affective touch from isolated
      individuals to truly interacting dyads. We have designed an ecological paradigm
      where romantic partners interact only via touch and we manipulate their empathic
      states. Simultaneously, we collected their autonomic activity (skin conductance,
      pulse, respiration). Fourteen couples participated to the experiment. We found
      that interpersonal touch increased coupling of electrodermal activity between the
      interacting partners, regardless the intensity and valence of the emotion felt.
      In addition, physical touch induced strong and reliable changes in physiological
      states within individuals. These results support an instrumental role of
      interpersonal touch for affective support in close relationships. Furthermore,
      they suggest that touch alone allows the emergence of a somatovisceral resonance
      between interacting individuals, which in turn is likely to form the
      prerequisites for emotional contagion and empathy. 

PMID- 24734010
TI  - Consequences of early postnatal benzodiazepines exposure in rats. I. Cognitive
      like behavior.
AB  - Clinical and experimental studies suggest possible risks associated with the
      repeated administration of benzodiazepines (BZDs) during the prenatal or early
      postnatal period on further development and behavior. In the present study, we
      assess short- and long-term effects of early exposure to clonazepam (CZP) on
      cognitive tasks. CZP (0.5 or 1.0 mg/kg/day) was administered from postnatal day
      (P)7 until P11, and animals were exposed to the following behavioral tests at
      different developmental stages: (1) a homing response (HR) test, which exploits
      the motivation of a rat pup to reach its home nest, was administered on P12, P15,
      P18 and P23 rats; (2) passive avoidance was tested in three trials (at 0, 2 and
      24 h intervals) on P12, P15, P18, P25 and P32 rats; (3) within- and between
      session habituation was tested in an open field (OF) at P70; and (4) a long-term
      memory (LTM) version of the Morris water maze (MWM) was tested at P80. A 1.0
      mg/kg dose of CZP extended latency in the HR and decreased the number of correct
      responses when tested at P12 and P23. In the first trial of the passive avoidance
      test, latency to enter a dark compartment was shorter in the CZP-exposed rats.
      Both treated and control animals older than P15 learned the passive-avoidance
      response at the same rate. Irrespective of the treatments, all adult animals
      showed within-session habituation. Between-session habituation, however, was
      found only in the controls. With respect to the MWM test, all animals learned to
      reach the platform, but animals exposed to higher doses of CZP spent more time
      swimming in the first acquisition test. No difference between groups was found in
      a repeated acquisition test (10 and 40 days after the first acquisition test).
      The results of the present study show that even short-term exposure to CZP alters
      behavioral responsiveness in pre-weaning, juvenile and adult animals. Not only
      were changes observed on conventional cognitive tests in our study, but the
      changes also seem to be related to emotional/motivational responsiveness. 

PMID- 24734011
TI  - Enfacing others but only if they are nice to you.
AB  - Experiencing tactile facial stimulation while seeing synchronous stimuli on the
      face of another individual induces "enfacement," i.e., the subjective illusory
      experience of ownership of the other's face (explicit measure) and the
      attribution of the others' facial features to one's own face (implicit measure).
      Here we expanded previous knowledge by investigating if the tendency to include
      the other into one's own representation is influenced by positive or negative
      interpersonal attitudes derived either from consolidated socio-cultural
      stereotypes or from newly acquired, short-term individual interactions with a
      specific person. To this aim, we tested in Caucasian white participants the
      enfacement with a white and a black confederate, before and after an experimental
      procedure inducing a positive or negative perception of each of them. The results
      show that the subjective experience of enfacement with in- and out-group others
      before and after the manipulation is similar. The bias in attributing other's
      facial features to one's own face after synchronous stroking was, instead,
      dependent on whether the other person was positively perceived, independently of
      his/her ethnicity. Thus, we show that realistic positive face-to-face
      interactions are more effective than consolidated racial biases in influencing
      the strength of self-attribution of another persons' facial features in the
      context of multisensory illusions. Results suggest that positive interpersonal
      interactions might powerfully change the plasticity of self-other
      representations. 

PMID- 24734012
TI  - EEG activity represents the correctness of perceptual decisions trial-by-trial.
AB  - Performance monitoring is an executive function, which we depend on for detecting
      and evaluating the consequences of our behavior. Although event related
      potentials (ERPs) have revealed the existence of differences after correct and
      incorrect decisions, it is not known whether there is a trial-by-trial
      representation of the accuracy of the decision. We recorded the
      electroencephalographic activity (EEG) while participants performed a perceptual
      discrimination task, with two levels of difficulty, in which they received
      immediate feedback. Receiver Operating Characteristic (ROC) analyses were used to
      reveal two components that convey trial-by-trial representations of the
      correctness of the decisions. Firstly, the performance monitoring-related
      negativity (PM-N), a negative deflection whose amplitude is higher (more
      negative) after incorrect trials. Secondly, the performance monitoring-related
      positivity (PM-P), a positive deflection whose amplitude is higher after
      incorrect trials. During the time periods corresponding to these components,
      trials can be accurately categorized as correct or incorrect by looking at the
      EEG activity; this categorization is more accurate when based on the PM-P. We
      further show that the difficulty of the discrimination task has a different
      effect on each component: after easy trials the latency of the PM-N is shorter
      and the amplitude of the PM-P is higher than after difficult trials. Consistent
      with previous interpretations of performance-related ERPs, these results suggest
      a functional differentiation between these components. The PM-N could be related
      to an automatic error detection system, responsible for fast behavioral
      corrections of ongoing actions, while the PM-P could reflect the difference
      between expected and actual outcomes and be related to long-term changes in the
      decision process. 

PMID- 24734013
TI  - The effect of haptic cues on motor and perceptual based implicit sequence
      learning.
AB  - We introduced haptic cues to the serial reaction time (SRT) sequence learning
      task alongside the standard visual cues to assess the relative contributions of
      visual and haptic stimuli to the formation of motor and perceptual memories. We
      used motorized keys to deliver brief pulse-like displacements to the resting
      fingers, expecting that the proximity and similarity of these cues to the
      subsequent response motor actions (finger-activated key-presses) would strengthen
      the motor memory trace in particular. We adopted the experimental protocol
      developed by Willingham (1999) to explore whether haptic cues contribute
      differently than visual cues to the balance of motor and perceptual learning. We
      found that sequence learning occurs with haptic stimuli as well as with visual
      stimuli and we found that irrespective of the stimuli (visual or haptic) the SRT
      task leads to a greater amount of motor learning than perceptual learning. 

PMID- 24734014
TI  - Auditory feedback of one's own voice is used for high-level semantic monitoring:
      the "self-comprehension" hypothesis.
AB  - What would it be like if we said one thing, and heard ourselves saying something
      else? Would we notice something was wrong? Or would we believe we said the thing
      we heard? Is feedback of our own speech only used to detect errors, or does it
      also help to specify the meaning of what we say? Comparator models of self
      monitoring favor the first alternative, and hold that our sense of agency is
      given by the comparison between intentions and outcomes, while inferential models
      argue that agency is a more fluent construct, dependent on contextual inferences
      about the most likely cause of an action. In this paper, we present a theory
      about the use of feedback during speech. Specifically, we discuss inferential
      models of speech production that question the standard comparator assumption that
      the meaning of our utterances is fully specified before articulation. We then
      argue that auditory feedback provides speakers with a channel for high-level,
      semantic "self-comprehension". In support of this we discuss results using a
      method we recently developed called Real-time Speech Exchange (RSE). In our first
      study using RSE (Lind et al., in press) participants were fitted with headsets
      and performed a computerized Stroop task. We surreptitiously recorded words they
      said, and later in the test we played them back at the exact same time that the
      participants uttered something else, while blocking the actual feedback of their
      voice. Thus, participants said one thing, but heard themselves saying something
      else. The results showed that when timing conditions were ideal, more than two
      thirds of the manipulations went undetected. Crucially, in a large proportion of
      the non-detected manipulated trials, the inserted words were experienced as self
      produced by the participants. This indicates that our sense of agency for speech
      has a strong inferential component, and that auditory feedback of our own voice
      acts as a pathway for semantic monitoring. We believe RSE holds great promise as
      a tool for investigating the role of auditory feedback during speech, and we
      suggest a number of future studies to serve this purpose. 

PMID- 24734015
TI  - The role of the habenula in drug addiction.
AB  - Interest in the habenula has greatly increased in recent years. The habenula is a
      small brain structure located posterior to the thalamus and adjacent to the third
      ventricle. Despite its small size, the habenula can be divided into medial
      habenula (MHb) and lateral habenula (LHb) nuclei that are anatomically and
      transcriptionally distinct. The habenula receives inputs from the limbic system
      and basal ganglia primarily via the stria medullaris. The fasciculus retroflexus
      is the primary habenular output from the habenula to the midbrain and governs
      release of glutamate onto gabaergic cells in the rostromedial tegmental nucleus
      (RMTg) and onto the interpeduncular nucleus. The resulting GABA released from
      RMTg neurons inactivates dopaminergic cells in the ventral tegmental
      area/substantia nigra compacta. Through this process, the habenula controls
      dopamine levels in the striatum. Thus, the habenula plays a critical role in
      reward and reward-associated learning. The LHb also modulates serotonin levels
      and norepinephrine release, while the MHb modulates acetylcholine. The habenula
      is a critical crossroad that influences the brain's response to pain, stress,
      anxiety, sleep, and reward. Dysfunction of the habenula has been linked to
      depression, schizophrenia, and the effects of drugs of abuse. This review focuses
      on the possible relationships between the habenula and drug abuse. 

PMID- 24734016
TI  - A review of neuroimaging studies of race-related prejudice: does amygdala
      response reflect threat?
AB  - Prejudice is an enduring and pervasive aspect of human cognition. An emergent
      trend in modern psychology has focused on understanding how cognition is linked
      to neural function, leading researchers to investigate the neural correlates of
      prejudice. Research in this area using racial group memberships has quickly
      highlighted the amygdala as a neural structure of importance. In this article, we
      offer a critical review of social neuroscientific studies of the amygdala in race
      related prejudice. Rather than the dominant interpretation that amygdala activity
      reflects a racial or outgroup bias per se, we argue that the observed pattern of
      sensitivity in this literature is best considered in terms of potential threat.
      More specifically, we argue that negative culturally-learned associations between
      black males and potential threat better explain the observed pattern of amygdala
      activity. Finally, we consider future directions for the field and offer specific
      experiments and predictions to directly address unanswered questions. 

PMID- 24734017
TI  - A problem-solving task specialized for functional neuroimaging: validation of the
      Scarborough adaptation of the Tower of London (S-TOL) using near-infrared
      spectroscopy.
AB  - Problem-solving is an executive function subserved by a network of neural
      structures of which the dorsolateral prefrontal cortex (DLPFC) is central.
      Whereas several studies have evaluated the role of the DLPFC in problem-solving,
      few standardized tasks have been developed specifically for use with functional
      neuroimaging. The current study adapted a measure with established validity for
      the assessment of problem-solving abilities to design a test more suitable for
      functional neuroimaging protocols. The Scarborough adaptation of the Tower of
      London (S-TOL) was administered to 38 healthy adults while hemodynamic
      oxygenation of the PFC was measured using 16-channel continuous-wave functional
      near-infrared spectroscopy (fNIRS). Compared to a baseline condition, problems
      that required two or three steps to achieve a goal configuration were associated
      with higher activation in the left DLPFC and deactivation in the medial PFC.
      Individuals scoring higher in trait deliberation showed consistently higher
      activation in the left DLPFC regardless of task difficulty, whereas individuals
      lower in this trait displayed less activation when solving simple problems. Based
      on these results, the S-TOL may serve as a standardized task to evaluate problem
      solving abilities in functional neuroimaging studies. 

PMID- 24734018
TI  - Isotropic non-white matter partial volume effects in constrained spherical
      deconvolution.
AB  - Diffusion-weighted (DW) magnetic resonance imaging (MRI) is a non-invasive
      imaging method, which can be used to investigate neural tracts in the white
      matter (WM) of the brain. Significant partial volume effects (PVEs) are present
      in the DW signal due to relatively large voxel sizes. These PVEs can be caused by
      both non-WM tissue, such as gray matter (GM) and cerebrospinal fluid (CSF), and
      by multiple non-parallel WM fiber populations. High angular resolution diffusion
      imaging (HARDI) methods have been developed to correctly characterize complex WM
      fiber configurations, but to date, many of the HARDI methods do not account for
      non-WM PVEs. In this work, we investigated the isotropic PVEs caused by non-WM
      tissue in WM voxels on fiber orientations extracted with constrained spherical
      deconvolution (CSD). Experiments were performed on simulated and real DW-MRI
      data. In particular, simulations were performed to demonstrate the effects of
      varying the diffusion weightings, signal-to-noise ratios (SNRs), fiber
      configurations, and tissue fractions. Our results show that the presence of non
      WM tissue signal causes a decrease in the precision of the detected fiber
      orientations and an increase in the detection of false peaks in CSD. We estimated
      35-50% of WM voxels to be affected by non-WM PVEs. For HARDI sequences, which
      typically have a relatively high degree of diffusion weighting, these adverse
      effects are most pronounced in voxels with GM PVEs. The non-WM PVEs become severe
      with 50% GM volume for maximum spherical harmonics orders of 8 and below, and
      already with 25% GM volume for higher orders. In addition, a low diffusion
      weighting or SNR increases the effects. The non-WM PVEs may cause problems in
      connectomics, where reliable fiber tracking at the WM-GM interface is especially
      important. We suggest acquiring data with high diffusion-weighting 2500-3000
      s/mm(2), reasonable SNR (~30) and using lower SH orders in GM contaminated
      regions to minimize the non-WM PVEs in CSD. 

PMID- 24734019
TI  - The multi-modal Australian ScienceS Imaging and Visualization Environment
      (MASSIVE) high performance computing infrastructure: applications in neuroscience
      and neuroinformatics research.
AB  - The Multi-modal Australian ScienceS Imaging and Visualization Environment
      (MASSIVE) is a national imaging and visualization facility established by Monash
      University, the Australian Synchrotron, the Commonwealth Scientific Industrial
      Research Organization (CSIRO), and the Victorian Partnership for Advanced
      Computing (VPAC), with funding from the National Computational Infrastructure and
      the Victorian Government. The MASSIVE facility provides hardware, software, and
      expertise to drive research in the biomedical sciences, particularly advanced
      brain imaging research using synchrotron x-ray and infrared imaging, functional
      and structural magnetic resonance imaging (MRI), x-ray computer tomography (CT),
      electron microscopy and optical microscopy. The development of MASSIVE has been
      based on best practice in system integration methodologies, frameworks, and
      architectures. The facility has: (i) integrated multiple different neuroimaging
      analysis software components, (ii) enabled cross-platform and cross-modality
      integration of neuroinformatics tools, and (iii) brought together neuroimaging
      databases and analysis workflows. MASSIVE is now operational as a nationally
      distributed and integrated facility for neuroinfomatics and brain imaging
      research. 

PMID- 24734020
TI  - Mechanisms of cellular fibrosis associated with cancer regimen-related
      toxicities.
AB  - Fibrosis is a common, persistent and potentially debilitating complication of
      chemotherapy and radiation regimens used for the treatment of cancer. The
      molecular mechanisms underlying fibrosis have been well studied and reveal
      overall processes that are largely ubiquitous. However, it is important to note
      that although the processes are similar, they result in cellular phenotypes that
      are highly tissue specific. These tissue specific differences may present
      opportunities for therapeutic interventions to prevent or treat this often
      irreversible condition. Data generated from animal models of cancer therapy
      related tissue toxicities have revealed that the signaling pathways involved in
      fibrosis are the same as those involved in the normal injury response and include
      the transforming growth factor beta superfamily and a range of pro-inflammatory
      cytokines. The critical difference between normal wound healing and fibrosis
      development appears to be, that in fibrosis, these signaling pathways escape
      normal cellular regulation. As a result, an injury state is maintained and
      processes involved in normal healing are usurped. There are a few, if any,
      therapeutics that effectively prevent or treat fibrosis in patients.
      Consequently, cancer survivors may be chronically plagued with a variety of life
      altering fibrosis-related symptoms. Uncovering the signaling pathways that drive
      cellular fibrosis is paramount to the development of specific therapeutics that
      will mitigate this potentially devastating condition. 

PMID- 24734021
TI  - Systems biology approaches to understanding the cause and treatment of heart,
      lung, blood, and sleep disorders.

PMID- 24734023
TI  - The role IL-1 in tumor-mediated angiogenesis.
AB  - Tumor angiogenesis is one of the hallmarks of tumor progression and is essential
      for invasiveness and metastasis. Myeloid inflammatory cells, such as immature
      myeloid precursor cells, also termed myeloid-derived suppressor cells (MDSCs),
      neutrophils, and monocytes/macrophages, are recruited to the tumor
      microenvironment by factors released by the malignant cells that are subsequently
      "educated" in situ to acquire a pro-invasive, pro-angiogenic, and
      immunosuppressive phenotype. The proximity of myeloid cells to endothelial cells
      (ECs) lining blood vessels suggests that they play an important role in the
      angiogenic response, possibly by secreting a network of cytokines/chemokines and
      inflammatory mediators, as well as via activation of ECs for proliferation and
      secretion of pro-angiogenic factors. Interleukin-1 (IL-1) is an "alarm,"
      upstream, pro-inflammatory cytokine that is generated primarily by myeloid cells.
      IL-1 initiates and propagates inflammation, mainly by inducing a local cytokine
      network and enhancing inflammatory cell infiltration to affected sites and by
      augmenting adhesion molecule expression on ECs and leukocytes. Pro-inflammatory
      mediators were recently shown to play an important role in tumor-mediated
      angiogenesis and blocking their function may suppress tumor progression. In this
      review, we summarize the interactions between IL-1 and other pro-angiogenic
      factors during normal and pathological conditions. In addition, the feasibility
      of IL-1 neutralization approaches for anti-cancer therapy is discussed. 

PMID- 24734024
TI  - Differences in the phototaxis of pollen and nectar foraging honey bees are
      related to their octopamine brain titers.
AB  - The biogenic amine octopamine is an important neuromodulator, neurohormone and
      neurotransmitter in insects. We here investigate the role of octopamine signaling
      in honey bee phototaxis. Our results show that groups of bees differ naturally in
      their phototaxis. Pollen forgers display a lower light responsiveness than nectar
      foragers. The lower phototaxis of pollen foragers coincides with higher
      octopamine titers in the optic lobes but is independent of octopamine receptor
      gene expression. Increasing octopamine brain titers reduces responsiveness to
      light, while tyramine application enhances phototaxis. These findings suggest an
      involvement of octopamine signaling in honey bee phototaxis and possibly division
      of labor, which is hypothesized to be based on individual differences in sensory
      responsiveness. 

PMID- 24734022
TI  - The status of and future research into Myalgic Encephalomyelitis and Chronic
      Fatigue Syndrome: the need of accurate diagnosis, objective assessment, and
      acknowledging biological and clinical subgroups.
AB  - Although Myalgic Encephalomyelitis (ME) and Chronic Fatigue Syndrome (CFS) are
      used interchangeably, the diagnostic criteria define two distinct clinical
      entities. Cognitive impairment, (muscle) weakness, circulatory disturbances,
      marked variability of symptoms, and, above all, post-exertional malaise: a long
      lasting increase of symptoms after a minor exertion, are distinctive symptoms of
      ME. This latter phenomenon separates ME, a neuro-immune illness, from chronic
      fatigue (syndrome), other disorders and deconditioning. The introduction of the
      label, but more importantly the diagnostic criteria for CFS have generated much
      confusion, mostly because chronic fatigue is a subjective and ambiguous notion.
      CFS was redefined in 1994 into unexplained (persistent or relapsing) chronic
      fatigue, accompanied by at least four out of eight symptoms, e.g., headaches and
      unrefreshing sleep. Most of the research into ME and/or CFS in the last decades
      was based upon the multivalent CFS criteria, which define a heterogeneous patient
      group. Due to the fact that fatigue and other symptoms are non-discriminative,
      subjective experiences, research has been hampered. Various authors have
      questioned the physiological nature of the symptoms and qualified ME/CFS as
      somatization. However, various typical symptoms can be assessed objectively using
      standardized methods. Despite subjective and unclear criteria and measures,
      research has observed specific abnormalities in ME/CFS repetitively, e.g.,
      immunological abnormalities, oxidative and nitrosative stress, neurological
      anomalies, circulatory deficits and mitochondrial dysfunction. However, to
      improve future research standards and patient care, it is crucial that patients
      with post-exertional malaise (ME) and patients without this odd phenomenon are
      acknowledged as separate clinical entities that the diagnosis of ME and CFS in
      research and clinical practice is based upon accurate criteria and an objective
      assessment of characteristic symptoms, as much as possible that well-defined
      clinical and biological subgroups of ME and CFS patients are investigated in more
      detail, and that patients are monitored before, during and after interventions
      with objective measures and biomarkers. 

PMID- 24734025
TI  - Differences in cerebral cortical anatomy of left- and right-handers.
AB  - The left and right sides of the human brain are specialized for different kinds
      of information processing, and much of our cognition is lateralized to an extent
      toward one side or the other. Handedness is a reflection of nervous system
      lateralization. Roughly ten percent of people are mixed- or left-handed, and they
      show an elevated rate of reductions or reversals of some cerebral functional
      asymmetries compared to right-handers. Brain anatomical correlates of left
      handedness have also been suggested. However, the relationships of left
      handedness to brain structure and function remain far from clear. We carried out
      a comprehensive analysis of cortical surface area differences between 106 left
      handed subjects and 1960 right-handed subjects, measured using an automated
      method of regional parcellation (FreeSurfer, Destrieux atlas). This is the
      largest study sample that has so far been used in relation to this issue. No
      individual cortical region showed an association with left-handedness that
      survived statistical correction for multiple testing, although there was a
      nominally significant association with the surface area of a previously
      implicated region: the left precentral sulcus. Identifying brain structural
      correlates of handedness may prove useful for genetic studies of cerebral
      asymmetries, as well as providing new avenues for the study of relations between
      handedness, cerebral lateralization and cognition. 

PMID- 24734027
TI  - Morphology, phylogeny, and ecology of the aphelids (Aphelidea, Opisthokonta) and
      proposal for the new superphylum Opisthosporidia.
AB  - The aphelids are a small group of intracellular parasitoids of common species of
      eukaryotic phytoplankton with three known genera Aphelidium, Amoeboaphelidium,
      and Pseudaphelidium, and 10 valid species, which form along with related
      environmental sequences a very diversified group. The phyla Microsporidia and
      Cryptomycota, and the class Aphelidea have recently been considered to be a deep
      branch of the Holomycota lineage forming the so called the ARM-clade which is
      sister to the fungi. In this review we reorganize the taxonomy of ARM-clade, and
      establish a new superphylum the Opisthosporidia with three phyla: Aphelida phyl.
      nov., Cryptomycota and Microsporidia. We discuss here all aspects of aphelid
      investigations: history of our knowledge, life cycle peculiarities, the
      morphology (including the ultrastructure), molecular phylogeny, ecology, and
      provide a taxonomic revision of the phylum supplied with a list of species. We
      compare the aphelids with their nearest relatives, the species of Rozella, and
      improve the diagnosis of the phylum Cryptomycota. 

PMID- 24734026
TI  - How low can you go? Changing the resolution of novel complex objects in visual
      working memory according to task demands.
AB  - In three experiments we manipulated the resolution of novel complex objects in
      visual working memory (WM) by changing task demands. Previous studies that
      investigated the trade-off between quantity and resolution in visual WM yielded
      mixed results for simple familiar stimuli. We used the contralateral delay
      activity as an electrophysiological marker to directly track the deployment of
      visual WM resources while participants preformed a change-detection task. Across
      three experiments we presented the same novel complex items but changed the task
      demands. In Experiment 1 we induced a medium resolution task by using change
      trials in which a random polygon changed to a different type of polygon and
      replicated previous findings showing that novel complex objects are represented
      with higher resolution relative to simple familiar objects. In Experiment 2 we
      induced a low resolution task that required distinguishing between polygons and
      other types of stimulus categories, but we failed in finding a corresponding
      decrease in the resolution of the represented item. Finally, in Experiment 3 we
      induced a high resolution task that required discriminating between highly
      similar polygons with somewhat different contours. This time, we observed an
      increase in the item's resolution. Our findings indicate that the resolution for
      novel complex objects can be increased but not decreased according to task
      demands, suggesting that minimal resolution is required in order to maintain
      these items in visual WM. These findings support studies claiming that capacity
      and resolution in visual WM reflect different mechanisms. 

PMID- 24734028
TI  - Co-inoculation of aflatoxigenic and non-aflatoxigenic strains of Aspergillus
      flavus to study fungal invasion, colonization, and competition in maize kernels.
AB  - A currently utilized pre-harvest biocontrol method involves field inoculations
      with non-aflatoxigenic Aspergillus flavus strains, a tactic shown to
      strategically suppress native aflatoxin-producing strains and effectively
      decrease aflatoxin contamination in corn. The present in situ study focuses on
      tracking the invasion and colonization of an aflatoxigenic A. flavus strain
      (AF70), labeled with green fluorescent protein (GFP), in the presence of a non
      aflatoxigenic A. flavus biocontrol strain (AF36), to better understand the
      competitive interaction between these two strains in seed tissue of corn (Zea
      mays). Corn kernels that had been co-inoculated with GFP-labeled AF70 and wild
      type AF36 were cross-sectioned and observed under UV and blue light to determine
      the outcome of competition between these strains. After imaging, all kernels were
      analyzed for aflatoxin levels. There appeared to be a population difference
      between the co-inoculated AF70-GFP+AF36 and the individual AF70-GFP tests, both
      visually and with pixel count analysis. The GFP allowed us to observe that AF70
      GFP inside the kernels was suppressed up to 82% when co-inoculated with AF36
      indicating that AF36 inhibited progression of AF70-GFP. This was in agreement
      with images taken of whole kernels where AF36 exhibited a more robust external
      growth compared to AF70-GFP. The suppressed growth of AF70-GFP was reflected in a
      corresponding (upto 73%) suppression in aflatoxin levels. Our results indicate
      that the decrease in aflatoxin production correlated with population depression
      of the aflatoxigenic fungus by the biocontrol strain supporting the theory of
      competitive exclusion through robust propagation and fast colonization by the non
      aflatoxigenic fungus. 

PMID- 24734029
TI  - The earthworm-Verminephrobacter symbiosis: an emerging experimental system to
      study extracellular symbiosis.
AB  - ALMOST ALL LUMBRICID EARTHWORMS (OLIGOCHAETA: Lumbricidae) harbor extracellular
      species-specific bacterial symbionts of the genus Verminephrobacter
      (Betaproteobacteria) in their nephridia. The symbionts have a beneficial effect
      on host reproduction and likely live on their host's waste products. They are
      vertically transmitted and presumably associated with earthworms already at the
      origin of Lumbricidae 62-136 million years ago. The Verminephrobacter genomes
      carry signs of bottleneck-induced genetic drift, such as accelerated evolutionary
      rates, low codon usage bias, and extensive genome shuffling, which are
      characteristic of vertically transmitted intracellular symbionts. However, the
      Verminephrobacter genomes lack AT bias, size reduction, and pseudogenization,
      which are also common genomic hallmarks of vertically transmitted, intracellular
      symbionts. We propose that the opportunity for genetic mixing during part of the
      host-symbiont life cycle is the key to evade drift-induced genome erosion.
      Furthermore, we suggest the earthworm-Verminephrobacter association as a new
      experimental system for investigating host-microbe interactions, and especially
      for understanding genome evolution of vertically transmitted symbionts in the
      presence of genetic mixing.

PMID- 24734030
TI  - Regulation of immune reactivity by intercellular transfer.
AB  - It was recently proposed that T lymphocytes, which closely interact with APCs,
      can extract surface molecules from the presenting cells when they dissociate.
      These observations question the classical view of discrete interactions between
      phenotypically defined cell populations. In this review, we summarize some
      reports suggesting that membrane exchange at the immune synapse can be a vector
      for intercellular communication and envisage some consequences on the biology of
      T cells. 

PMID- 24734031
TI  - AIDing Chromatin and Transcription-Coupled Orchestration of Immunoglobulin Class
      Switch Recombination.
AB  - Secondary diversification of the antibody repertoire upon antigenic challenge, in
      the form of immunoglobulin heavy chain (IgH) class-switch recombination (CSR)
      endows mature, naive B cells in peripheral lymphoid organs with a limitless
      ability to mount an optimal humoral immune response, thus expediting pathogen
      elimination. CSR replaces the default constant (CH) region exons (CMU) of IgH
      with any of the downstream CH exons (Cgamma, Cepsilon, or Calpha), thereby
      altering effector functions of the antibody molecule. This process depends on,
      and is orchestrated by, activation-induced deaminase (AID), a DNA cytidine
      deaminase that acts on single-stranded DNA exposed during transcription of switch
      (S) region sequences at the IgH locus. DNA lesions thus generated are processed
      by components of several general DNA repair pathways to drive CSR. Given that AID
      can instigate DNA lesions and genomic instability, stringent checks are imposed
      that constrain and restrict its mutagenic potential. In this review, we will
      discuss how AID expression and substrate specificity and activity is rigorously
      enforced at the transcriptional, post-transcriptional, post-translational, and
      epigenetic levels, and how the DNA-damage response is choreographed with
      precision to permit targeted activity while limiting bystander catastrophe. 

PMID- 24734032
TI  - Innate and adaptive immune interactions at the fetal-maternal interface in
      healthy human pregnancy and pre-eclampsia.
AB  - Maternal immune tolerance of the fetus is indispensable for a healthy pregnancy
      outcome. Nowhere is this immune tolerance more important than at the fetal
      maternal interface - the decidua, the site of implantation, and placentation.
      Indeed, many lines of evidence suggest an immunological origin to the common
      pregnancy-related disorder, pre-eclampsia. Within the innate immune system,
      decidual NK cells and antigen presenting cells (including dendritic cells and
      macrophages) make up a large proportion of the decidual leukocyte population, and
      are thought to modulate vascular remodeling and trophoblast invasion. On the
      other hand, within the adaptive immune system, Foxp3(+) regulatory T cells are
      crucial for ensuring immune tolerance toward the semi-allogeneic fetus.
      Additionally, another population of CD4(+)HLA-G(+) suppressor T cells has also
      been identified as a potential player in the maintenance of immune tolerance.
      More recently, studies are beginning to unravel the potential interactions
      between the innate and the adaptive immune system within the decidua, that are
      required to maintain a healthy pregnancy. In this review, we discuss the recent
      advances exploring the complex crosstalk between the innate and the adaptive
      immune system during human pregnancy. 

PMID- 24734034
TI  - Splenic B-1a Cells Expressing CD138 Spontaneously Secrete Large Amounts of
      Immunoglobulin in Naive Mice.
AB  - B-1a cells constitutively secrete natural antibody that provides immediate
      protection against microbial pathogens and functions homeostatically to speed
      removal of apoptotic cell debris. Although B-1a cells are especially prominent in
      the peritoneal and pleural cavities, some B-1a cells reside in the spleen. A
      small subset of splenic B-1a cells in naive, unimmunized mice express CD138, a
      recognized plasma cell antigen, whereas the bulk of splenic B-1a cells are CD138
      negative. Splenic B-1a cells in toto have been shown to generate much more
      antibody per cell than peritoneal B-1a cells; however, specific functional
      information regarding CD138(+) splenic B-1a cells has been lacking. Here, we find
      a higher proportion of CD138(+) splenic B-1a cells spontaneously secrete more IgM
      as compared to CD138(-) B-1a cells. Moreover, IgM secreted by CD138(+) splenic B
      1a cells is skewed with respect to N-region addition, and some aspects of VH and
      JH utilization, as compared to CD138(-) splenic B-1a cells and peritoneal B-1a
      cells. The small population of CD138(+) splenic B-1a cells is likely responsible
      for a substantial portion of natural IgM and differs from IgM produced by other B
      1a cell subsets. 

PMID- 24734033
TI  - Genome-wide analysis of DNA methylation, copy number variation, and gene
      expression in monozygotic twins discordant for primary biliary cirrhosis.
AB  - Primary biliary cirrhosis (PBC) is an uncommon autoimmune disease with a
      homogeneous clinical phenotype that reflects incomplete disease concordance in
      monozygotic (MZ) twins. We have taken advantage of a unique collection consisting
      of genomic DNA and mRNA from peripheral blood cells of female MZ twins (n = 3
      sets) and sisters of similar age (n = 8 pairs) discordant for disease. We
      performed a genome-wide study to investigate differences in (i) DNA methylation
      (using a custom tiled four-plex array containing tiled 50-mers 19,084 randomly
      chosen methylation sites), (ii) copy number variation (CNV) (with a chip
      including markers derived from the 1000 Genomes Project, all three HapMap phases,
      and recently published studies), and/or (iii) gene expression (by whole-genome
      expression arrays). Based on the results obtained from these three approaches we
      utilized quantitative PCR to compare the expression of candidate genes.
      Importantly, our data support consistent differences in discordant twins and
      siblings for the (i) methylation profiles of 60 gene regions, (ii) CNV of 10
      genes, and (iii) the expression of 2 interferon-dependent genes. Quantitative PCR
      analysis showed that 17 of these genes are differentially expressed in discordant
      sibling pairs. In conclusion, we report that MZ twins and sisters discordant for
      PBC manifest particular epigenetic differences and highlight the value of the
      epigenetic study of twins. 

PMID- 24734035
TI  - Genome analysis of poplar LRR-RLP gene clusters reveals RISP, a defense-related
      gene coding a candidate endogenous peptide elicitor.
AB  - In plants, cell-surface receptors control immunity and development through the
      recognition of extracellular ligands. Leucine-rich repeat receptor-like proteins
      (LRR-RLPs) constitute a large multigene family of cell-surface receptors.
      Although this family has been intensively studied, a limited number of ligands
      has been identified so far, mostly because methods used for their identification
      and characterization are complex and fastidious. In this study, we combined
      genome and transcriptome analyses to describe the LRR-RLP gene family in the
      model tree poplar (Populus trichocarpa). In total, 82 LRR-RLP genes have been
      identified in P. trichocarpa genome, among which 66 are organized in clusters of
      up to seven members. In these clusters, LRR-RLP genes are interspersed by orphan,
      poplar-specific genes encoding small proteins of unknown function (SPUFs). In
      particular, the nine largest clusters of LRR-RLP genes (47 LRR-RLPs) include 71
      SPUF genes that account for 59% of the non-LRR-RLP gene content within these
      clusters. Forty-four LRR-RLP and 55 SPUF genes are expressed in poplar leaves,
      mostly at low levels, except for members of some clusters that show higher and
      sometimes coordinated expression levels. Notably, wounding of poplar leaves
      strongly induced the expression of a defense SPUF gene named Rust-Induced
      Secreted protein (RISP) that has been previously reported as a marker of poplar
      defense responses. Interestingly, we show that the RISP-associated LRR-RLP gene
      is highly expressed in poplar leaves and slightly induced by wounding. Both gene
      promoters share a highly conserved region of ~300 nucleotides. This led us to
      hypothesize that the corresponding pair of proteins could be involved in poplar
      immunity, possibly as a ligand/receptor couple. In conclusion, we speculate that
      some poplar SPUFs, such as RISP, represent candidate endogenous peptide ligands
      of the associated LRR-RLPs and we discuss how to investigate further this
      hypothesis. 

PMID- 24734036
TI  - Overexpression of SAMDC1 gene in Arabidopsis thaliana increases expression of
      defense-related genes as well as resistance to Pseudomonas syringae and
      Hyaloperonospora arabidopsidis.
AB  - It has been previously described that elevation of endogenous spermine levels in
      Arabidopsis could be achieved by transgenic overexpression of S
      Adenosylmethionine decarboxylase (SAMDC) or Spermine synthase (SPMS). In both
      cases, spermine accumulation had an impact on the plant transcriptome, with up
      regulation of a set of genes enriched in functional categories involved in
      defense-related processes against both biotic and abiotic stresses. In this work,
      the response of SAMDC1-overexpressing plants against bacterial and oomycete
      pathogens has been tested. The expression of several pathogen defense-related
      genes was induced in these plants as well as in wild type plants exposed to an
      exogenous supply of spermine. SAMDC1-overexpressing plants showed an increased
      tolerance to infection by Pseudomonas syringae and by Hyaloperonospora
      arabidopsidis. Both results add more evidence to the hypothesis that spermine
      plays a key role in plant resistance to biotic stress. 

PMID- 24734037
TI  - Hormonal crosstalk for root development: a combined experimental and modeling
      perspective.
AB  - Plants are sessile organisms and therefore they must adapt their growth and
      architecture to a changing environment. Understanding how hormones and genes
      interact to coordinate plant growth in a changing environment is a major
      challenge in developmental biology. Although a localized auxin concentration
      maximum in the root tip is important for root development, auxin concentration
      cannot change independently of multiple interacting hormones and genes. In this
      review, we discuss the experimental evidence showing that the POLARIS peptide of
      Arabidopsis plays an important role in hormonal crosstalk and root growth, and
      review the crosstalk between auxin and other hormones for root growth with and
      without osmotic stress. Moreover, we discuss that experimental evidence showing
      that, in root development, hormones and the associated regulatory and target
      genes form a network, in which relevant genes regulate hormone activities and
      hormones regulate gene expression. We further discuss how it is increasingly
      evident that mathematical modeling is a valuable tool for studying hormonal
      crosstalk. Therefore, a combined experimental and modeling study on hormonal
      crosstalk is important for elucidating the complexity of root development. 

PMID- 24734038
TI  - Despeckle Filtering for Multiscale Amplitude-Modulation Frequency-Modulation (AM
      FM) Texture Analysis of Ultrasound Images of the Intima-Media Complex.
AB  - The intima-media thickness (IMT) of the common carotid artery (CCA) is widely
      used as an early indicator of cardiovascular disease (CVD). Typically, the IMT
      grows with age and this is used as a sign of increased risk of CVD. Beyond
      thickness, there is also clinical interest in identifying how the composition and
      texture of the intima-media complex (IMC) changed and how these textural changes
      grow into atherosclerotic plaques that can cause stroke. Clearly though texture
      analysis of ultrasound images can be greatly affected by speckle noise, our goal
      here is to develop effective despeckle noise methods that can recover image
      texture associated with increased rates of atherosclerosis disease. In this
      study, we perform a comparative evaluation of several despeckle filtering
      methods, on 100 ultrasound images of the CCA, based on the extracted multiscale
      Amplitude-Modulation Frequency-Modulation (AM-FM) texture features and visual
      image quality assessment by two clinical experts. Texture features were extracted
      from the automatically segmented IMC for three different age groups. The
      despeckle filters hybrid median and the homogeneous mask area filter showed the
      best performance by improving the class separation between the three age groups
      and also yielded significantly improved image quality. 

PMID- 24734039
TI  - Physician perceptions on colonoscopy quality: results of a national survey of
      gastroenterologists.
AB  - Background. Quality indicators for colonoscopy have been developed, but the
      uptake of these metrics into practice is uncertain. Our aims were to assess
      physician perceptions regarding colonoscopy quality measurement and to quantify
      the perceived impact of quality measurement on clinical practice. Methods. We
      conducted in-person interviews with 15 gastroenterologists about their
      perceptions regarding colonoscopy quality. Results from these interviews informed
      the development of a 34-question web-based survey that was emailed to 1,500
      randomlyselected members of the American College of Gastroenterology. Results.
      160 invitations were undeliverable, and 167 out of 1340 invited physicians
      (12.5%) participated in the survey. Respondents and nonrespondents did not differ
      in age, sex, practice setting, or years since training. 38.8% of respondents
      receive feedback on their colonoscopy quality. The majority of respondents agreed
      with the use of completion rate (90%) and adenoma detection rate (83%) as quality
      indicators but there was less enthusiasm for withdrawal time (61%). 24% of
      respondents reported usually or always removing diminutive polyps solely to
      increase their adenoma detection rate, and 20% reported prolonging their
      procedure time to meet withdrawal time standards. Conclusions. A minority of
      respondents receives feedback on the quality of their colonoscopy. Interventions
      to increase continuous quality improvement in colonoscopy screening are needed. 

PMID- 24734040
TI  - Efficacy of i-Scan Imaging for the Detection and Diagnosis of Early Gastric
      Carcinomas.
AB  - We determined comparative efficacy of i-Scan for detection and diagnosis of
      gastric cancer. Ten patients diagnosed with early gastric cancer based on
      histopathological findings were analyzed. White light and i-Scan moving images
      recorded from these patients in twin mode were separated into white light and i
      Scan. Twelve endoscopists (three different skill levels) blinded to patient
      information evaluated the images. Correlation between demarcation accuracy and
      lesion brightness on still images was investigated. No significant differences
      were found in diagnostic accuracy between white light and i-Scan moving images
      for tumor detection rate (91.7% versus 90.8%, P = 0.777). Diagnostic accuracy of
      tumor size was comparable between novice and experienced endoscopists for i-Scan
      moving images (65.7% versus 71.1%, P = 0.528), whereas it was significantly lower
      for white light moving images (41.2% versus 79.5%, P = 0.019). Tumor demarcation
      accuracy was significantly better with white light than i-Scan still images
      (71.0% versus 65.8%, P = 0.033). Correlations between demarcation accuracy and
      brightness reached highs of 0.75 for white light and 0.89 for i-Scan imaging.
      Efficacy of i-Scan over that of white light imaging for detecting and diagnosing
      gastric cancer was not shown; however, the diagnostic capability of i-Scan can be
      improved if imaging conditions are optimized. 

PMID- 24734041
TI  - Acute Toxicity and Determination of the Active Constituents of Aqueous Extract of
      Uncaria tomentosa Bark in Hyphessobrycon eques.
AB  - Uncaria tomentosa is a medicinal plant used in folk medicine by Amazon tribes. In
      this study the constituents of aqueous extract of U. tomentosa bark were
      quantified by chromatographic technique and its lethal concentration 50 (48 h) in
      Hyphessobrycon eques was determined. The chromatography showed high levels of
      oxindole alkaloids, quinovic acid glycosides, and low molecular weight
      polyphenols. The CL50 48 h was 1816 mg/L. Fish showed behavior changes at
      concentrations above 2000 mg/L, accompanied by a significant decrease of
      dissolved oxygen. At the highest concentration 100% mortality was observed
      attributed to oxygen reduction by the amount of oxindole alkaloids, polyphenols
      accumulation of the extract in the gills, and the interaction of these compounds
      with dopamine. In conclusion, the aqueous extract of U. tomentosa did not alter
      the chemical components and it was shown that U. tomentosa has low toxicity to H.
      eques; therefore, it can be used safely in this species. 

PMID- 24734042
TI  - Fasting Leptin Is a Metabolic Determinant of Food Reward in Overweight and Obese
      Individuals during Chronic Aerobic Exercise Training.
AB  - Changes in food reward have been implicated in exercise-induced compensatory
      eating behaviour. However, the underlying mechanisms of food reward, and the
      physiological correlates of exercise-induced changes in food reward, are unknown.
      Methods. Forty-six overweight and obese individuals completed 12 weeks of aerobic
      exercise. Body composition, food intake, and fasting metabolic-related hormones
      were measured at baseline, week six, and postintervention. On separate days, the
      reward value of high-and-low-fat food (explicit liking and implicit wanting) was
      also assessed at baseline, week six, and postintervention. Results. Following the
      intervention, FM, FFM, and VO2peak improved significantly, while fasting leptin
      decreased. However, food intake or reward did not change significantly. Cross
      sectional analyses indicated that FM (P = 0.022) and FFM (P = 0.046) were
      associated with explicit liking for high-fat food, but implicit wanting was
      associated with FM only (P = 0.005). Fasting leptin was associated with liking (P
      = 0.023) and wanting (P = 0.021) for high-fat food. Furthermore, a greater
      exercise-induced decline in fasting leptin was associated with increased liking
      (P = 0.018). Conclusion. These data indicate that food reward has a number of
      physiological correlates. In particular, fasting leptin appears to play an active
      role in mediating food reward during exercise-induced weight loss. 

PMID- 24734043
TI  - Modified glomerular filtration rate-estimating equations developed in asiatic
      population for chinese patients with type 2 diabetes.
AB  - Objectives. To evaluate eight modified equations developed in Asiatic populations
      in type 2 diabetic patients in China. Methods. A total of 209 Chinese patients
      with type 2 diabetes were recruited. Using the technetium-99m
      diethylenetriaminepentaacetic acid-glomerular filtration rate (GFR) to act as the
      reference, comparisons of their efficiency to estimate GFR in the subjects were
      made between various equations. Results. Median of difference of the Chinese
      equation 1 was the lowest (median of difference, 0.51 mL/min/1.73 m(2)). Median
      percent of absolute difference of the Chinese equation 2 was less than those of
      the other equations (26.97 versus ranged from 32.54 to 37.61 mL/min/1.73 m(2), [P
      < 0.001 for all]). Precision of the simplified reexpressed MDRD equation was the
      best (92.9 mL/min/1.73 m(2)). Accuracies of the Chinese equation 2 were greater
      (P < 0.05 for all). There was also an improvement in chronic kidney disease (CKD)
      stage misclassification of the Chinese equation 2 (55.0 versus ranged from 61.2
      to 64.6%, [P < 0.001 for all]). However, the 30% accuracies of all the equations
      were less than 70%. Conclusions. Our study highlighted a limitation in the use of
      the above equations in the majority of Chinese diabetic subjects. A better
      equation is needed in order to give an accurate estimation of GFR in type 2
      diabetic patients in China. 

PMID- 24734044
TI  - Adipocytokines, metabolic syndrome, and exercise.

PMID- 24734045
TI  - Bone mineral density in children and adolescents with congenital adrenal
      hyperplasia.
AB  - Chronic glucocorticoid therapy is associated with reduced bone mineral density.
      In paediatric patients with congenital adrenal hyperplasia, increased levels of
      androgens could not only counteract this effect, but could also advance bone age,
      with interference in the evaluation of densitometry. We evaluate bone mineral
      density in paediatric patients with classic congenital adrenal hyperplasia taking
      into account chronological and bone ages at the time of the measurement. Patients
      aged between 5 and 19 years underwent radiography of the hand and wrist followed
      by total body and lumbar spine densitometry. Chronological and bone ages were
      used in the scans interpretation. In fourteen patients, mean bone mineral density
      Z-score of total body to bone age was -0.76 and of lumbar spine to bone age was 
      0.26, lower than those related to chronological age (+0.03 and +0.62, resp.).
      Mean Z-score differences were statistically significant (P = 0.004 for total body
      and P = 0.003 for lumbar spine). One patient was classified as having low bone
      mineral density only when assessed by bone age. We conclude that there was a
      reduction in the bone mineral density Z-score in classic congenital adrenal
      hyperplasia paediatric patients when bone age was taken into account instead of
      chronological age. 

PMID- 24734046
TI  - Detection of Integrase Gene in E. coli Isolated from Pigs at Different Stages of
      Production System.
AB  - Integrons are one of the genetic elements involved in the acquisition of
      antibiotic resistance. The aim of the present research is to investigate the
      presence of integrons in commensal Escherichia coli (E. coli) strains, isolated
      from pigs at different stages of production system and from the environment in an
      Argentinian farm. Five sows postpartum and five randomly chosen piglets from each
      litter were sampled by rectal swabs. They were sampled again at day 21 and at day
      70. Environmental samples from the farm were also obtained. E. coli containing
      any integron class or combination of both integrons was detected by polymerase
      chain reaction in 100% of sows and in piglets at different stages of production:
      farrowing pen stage 68.1%;, weaning 60%, and growing/finishing 85.8%, showing an
      increase along the production system. From environmental samples 78.4% of E. coli
      containing any integron class was detected. We conclude that animals and farm
      environment can act as reservoirs for potential spread of resistant bacteria by
      means of mobile genetic elements as integrons, which has a major impact on
      production of food animals and that can reach man through the food chain,
      constituting a problem for public health. 

PMID- 24734047
TI  - Escherichia coli Strains Isolated from the Uteri Horn, Mouth, and Rectum of
      Bitches Suffering from Pyometra: Virulence Factors, Antimicrobial
      Susceptibilities, and Clonal Relationships among Strains.
AB  - Pyometra is recognized as one of the main causes of disease and death in the
      bitch, and Escherichia coli is the major pathogen associated with this disease.
      In this study, 70 E. coli isolates from the uteri horn, mouth, and rectum of
      bitches suffering from the disease and 43 E. coli isolates from the rectum of
      clinically healthy bitches were examined for the presence of uropathogenic
      virulence genes and susceptibility to antimicrobial drugs. DNA profiles of
      isolates from uteri horn and mouth in bitches with pyometra were compared by REP,
      ERIC, and BOX-PCR. Virulence gene frequencies detected in isolates from canine
      pyometra were as follows: 95.7% fim, 27.1% iss, 25.7% hly, 18.5% iuc, and 17.1%
      usp. Predominant resistance was determined for cephalothin, ampicillin, and
      nalidixic acid among the isolates from all sites examined. Multidrug resistance
      was found on ~ 50% pyometra isolates. Using the genotypic methods some isolates
      from uteri, pus, and saliva of the same bitch proved to have identical DNA
      profiles which is a reason for concern due to the close relationship between
      household pets and humans. 

PMID- 24734048
TI  - Factors Associated with Acute Malnutrition among Children Admitted to a Diarrhoea
      Treatment Facility in Bangladesh.
AB  - To assess the risk factors for acute malnutrition (weight-for-height z-score
      (WHZ) < -2), a case-control study was conducted during June-September 2012 in 449
      children aged 6-59 months (178 with WHZ < -2 and 271 comparing children with WHZ
      >= -2 and no edema) admitted to the Dhaka Hospital of icddr,b in Bangladesh. The
      overall mean +/- SD age was 12.0 +/- 7.6 months, 38.5% (no difference between
      case and controls). The mean +/- SD WHZ of cases and controls was -3.24 +/- 1.01
      versus -0.74 +/- 0.95 (P < 0.001), respectively. Logistic regression analysis
      revealed that children with acute malnutrition were more likely than controls to
      be older (age > 1 year) (adjusted OR (AOR): 3.1, P = 0.004); have an
      undernourished mother (body mass index < 18.5), (AOR: 2.8, P = 0.017); have a
      father with no or a low-paying job (AOR: 5.8, P < 0.001); come from a family
      having a monthly income of <10,000 taka, (1 US$ = 80 taka) (AOR: 2.9, P = 0.008);
      and often have stopped predominant breastfeeding before 4 months of age (AOR:
      2.7, P = 0.013). Improved understanding of these characteristics enables the
      design and targeting of preventive-intervention programs of childhood acute
      malnutrition. 

PMID- 24734051
TI  - Alignment is the Most Efficient Tool in the Management of the Pharmaceutical
      Turbulent Market.

PMID- 24734049
TI  - Workplace-related traumatic injuries: insights from a rapidly developing Middle
      Eastern country.
AB  - Traumatic workplace-related injuries (WRIs) carry a substantial negative impact
      on the public health worldwide. We aimed to study the incidence and outcomes of
      WRIs in Qatar. We conducted occupational injury surveillance for all WRI patients
      between 2010 and 2012. A total of 5152 patients were admitted to the level 1
      trauma unit in Qatar, of which 1496 (29%) sustained WRI with a mean age of 34.3
      +/- 10.3. Fall from height (FFH) (51%) followed by being struck by heavy objects
      (FHO) (18%) and motor vehicle crashes (MVC) (17%) was the commonest mechanism of
      injury (MOI). WRI patients were mainly laborers involved in industrial work
      (43%), transportation (18%), installation/repair (12%), carpentry (9%), and
      housekeeping (3%). Use of protective device was not observed in 64% of cases. The
      mean ISS was 11.7 +/- 8.9, median ICU stay was 3 days (1-64), and total hospital
      stay was 6 days (1-192). The overall case fatality was 3.7%. Although the
      incidence of WRI in Qatar is quite substantial, its mortality rate is relatively
      low in comparison to other countries of similar socioeconomic status. Prolonged
      hospital stay and treatment exert a significant socioeconomic burden on the
      nation's and families' resources. Focused and efficient injury prevention
      strategies are mandatory to prevent future WRI. 

PMID- 24734050
TI  - Neonates in Ahmedabad, India, during the 2010 heat wave: a climate change
      adaptation study.
AB  - Health effects from climate change are an international concern with urban areas
      at particular risk due to urban heat island effects. The burden of disease on
      vulnerable populations in non-climate-controlled settings has not been well
      studied. This study compared neonatal morbidity in a non-air-conditioned hospital
      during the 2010 heat wave in Ahmedabad to morbidity in the prior and subsequent
      years. The outcome of interest was neonatal intensive care unit (NICU) admissions
      for heat. During the months of April, May, and June of 2010, 24 NICU admissions
      were for heat versus 8 and 4 in 2009 and 2011, respectively. Both the effect of
      moving the maternity ward and the effect of high temperatures were statistically
      significant, controlling for each other. Above 42 degrees Celsius, each daily
      maximum temperature increase of a degree was associated with 43% increase in heat
      related admissions (95% CI 9.2-88%). Lower floor location of the maternity ward
      within hospital which occurred after the 2010 heat wave showed a protective
      effect. These findings demonstrate the importance of simple surveillance measures
      in motivating a hospital policy change for climate change adaptation-here
      relocating one ward-and the potential increasing health burden of heat in non
      climate-controlled institutions on vulnerable populations. 

PMID- 24734052
TI  - A review of medication errors in iran: sources, underreporting reasons and
      preventive measures.
AB  - Medication error (ME) is the most common preventable cause of adverse drug events
      which negatively affects patient safety. Inadequate, low-quality studies plus
      wide estimation variations in ME from developing countries including Iran,
      decreases the reliability of ME evaluations. To clarify sources, underreporting
      reasons and preventive measures of MEs, we reviewed Iran current available
      literature. We searched Scopus, WOS, PubMed, CINAHL, EBSCOHOST and Persian
      databases (IranMedex, and SID) up to October 2012. Two authors independently
      selected and one reviewed and extracted data. Results reported by more than 30%
      of studies considered as the most important topics. Finally 25 articles were
      included. All study designs were cross-sectional (except for two interventional
      studies) and in hospital settings. Nursing staff and students were the most
      observed populations. Individual factor, with "inadequate knowledge of
      medication" as its most frequent reason, were the mostly reported source of MEs.
      Fear and reporting process were two most important reporting barriers. The sense
      of being reprimanded and ignoring to report respectively were their most frequent
      factors. Anti-infectives were the most frequent drugs involved in MEs. Preventive
      measures were varied and reporting of their effectiveness was inconsistent. There
      are still many research gaps which need to be explored by further studies. Based
      on our findings, further researches may be focused on design, implementation, and
      evaluation of a ME reporting system as groundwork, assessing systems-related
      factors to ME alongside individual factors and evaluating the effectiveness of
      preventive measures for MEs in trials. 

PMID- 24734053
TI  - Formulation and In-vitro Characterization of Sustained Release Matrix Type Ocular
      Timolol Maleate Mini-Tablet.
AB  - The purpose of this study was preparation and evaluation of sustained release
      matrix type ocular mini-tablets of timolol maleate, as a potential formulation
      for the treatment of glaucoma. Following the initial studies on timolol maleate
      powder, it was formulated into ocular mini-tablets. The polymers investigated in
      this study included cellulose derivatives (HEC, CMC, EC) and Carbopol 971P.
      Mannitol was used as the solubilizing agent and magnesium stearate as the
      lubricant. Mini-tablets were prepared by through mixing of the ingredients,
      followed by direct compression. All the prepared formulations were evaluated in
      terms of physicochemical tests, including uniformity of weight, thickness,
      crushing strength, friability and in-vitro drug release. Four groups of
      formulations were prepared. The presence of different amounts of cellulose
      derivatives or Carbopol 971P, alone, was studied in group A formulations. In
      group B formulations, the effect of adding Carbopol 971P alongside different
      cellulose derivatives was investigated. Group C formulations were made by
      including mannitol as the solubilizing agent, alongside Carbopol 971P and a
      cellulose derivative. In group D formulations, mini-tablets were made using
      Carbopol 971P, alongside two different cellulose derivative. The selected
      formulation (C1) contained ethyl cellulose, Carbopol 971P, mannitol and magnesium
      stearate, which showed almost 100% drug release over 5 h. Based on kinetic
      studies, this formulation was found to best fit the zero-order model of drug
      release. However, the Higuchi and Hixson -Crowell models also showed a good fit.
      Hence, overall, formulation C1 was chosen as the best formulation. 

PMID- 24734054
TI  - Pharmacokinetics and pharmacodynamics of gliclazide from immediate and modified
      release formulation tablets in rats.
AB  - The objective of the study was to compare pharmacokinetic and pharmacodynamic
      parameters of gliclazide after administration of immediate (IR) and modified
      release (MR) tablets. The experiment included rats with both normoglycemia and
      streptozocin (STZ)-induced hyperglycemia. Several MR formulations were designed
      and in-vitro drug release profile was assessed by a dissolution test. For the
      further in-vivo study the most suitable formulation was chosen. For
      pharmacokinetic analysis concentrations of gliclazide in plasma were determined
      by a validated high performance liquid chromatography (HPLC) method with UV
      detection. Pharmacodynamic efficacy of the drug was evaluated by measuring blood
      glucose concentrations. Gliclazide bioavailability was totally different for two
      formulations in both healthy and diabetic rats based on area under the curve
      (AUC), time to peak concentration (tmax) and peak concentration (Cmax). Reduction
      of blood glucose level was significantly higher after the administration of IR
      than MR formulation. The highest pharmacodynamic efficacy of gliclazide was
      observed in the normal animals group after administration of the IR tablets,
      while hypoglycemic effect of the drug was diminished in animals with induced
      diabetes. Our study suggested that results of reduction in blood glucose level
      for STZ-induced groups were not comparable with pharmacodynamic effect for normal
      group. It may be assumed that a decrease in glycemia in healthy subjects might
      not be a suitable factor for characterizing anti-diabetic drugs. 

PMID- 24734055
TI  - Mathematical modeling of the release of active ingredients from a contraceptive
      patch: ortho evra((r)) as a case study.
AB  - Contraceptive patches have become a frequently used contraceptive method. We
      present a mathematical model that describes the serum concentration profiles of
      Norelgestromin (NGMN) and Ethinylestradiol (EE) released from the contraceptive
      patch Ortho Evra((r)). We propose a simple one-compartment model based on
      pharmacokinetics data reported in previous studies. The model assumes a time
      dependent release rate and a first order elimination rate for each of the active
      ingredients contained in the patch. The model was applied to noncompliance
      scenarios, such as total and partial detachment of the patch or prolonged use
      without patch replacement. The proposed model adequately describes the clinically
      observed evolution of NGMN and EE in serum. Predictions from the model were
      successfully validated using reported experimental data of serum concentrations
      of NGMN and EE. This simple model can be a valuable tool to predict
      pharmacokinetic profiles in diverse scenarios such us non-compliance situations.
      Alternatively, the model can be conveniently adapted to anticipate the effect of
      variations on patch characteristics such as differences in contact area, doses,
      materials, among others. 

PMID- 24734057
TI  - Formulation and Evaluation of In-vitro Characterization of Gastic-Mucoadhesive
      Microparticles/Discs Containing Metformin Hydrochloride.
AB  - The present study involves preparation and evaluation of gastric-mucoadhesive
      microparticles with Metformin Hydrochloride as model drug for prolongation of
      gastric residence time. The microparticles were prepared by the emulsification
      solvent evaporation technique using polymers of Carbomer 934p (CP) and
      Ethylcellulose (EC). The microparticles were prepared by emulsion solvent
      evaporation method (O1/O2). Disc formulations were prepared by direct compression
      technique from microparticles. In the current study, gastric-mucoadhesive
      microparticles with different polymers ratios (CP:EC) were prepared and were
      characterized by encapsulation efficiency, particle size, flowability,
      mucoadhesive property and drug release studies. The best polymers ratio was 1:3
      (F2) with Carbomer 934p (as mucoadhesive polymer) and ethylcellulose (as
      retardant polymer), respectively. The production yield microparticles F2 showed
      98.80%, mean particle size 933.25 um and loading efficiency %98.44. The results
      were found that microparticle discs prepared had slower release than
      microparticles (p > o.o5). The microparticles exhibited very good percentage of
      mucoadhesion and flowability properties. The release of drug was prolonged to 8 h
      (71.65-82.22%) when incorporated into mucoadhesive microparticles. The poor
      bioavailability of metformine is attributed to short retention of its dosage form
      at the absorption sites (in upper gastrointestinal tract). The results of
      mucoadhesion study showed better retention of metformine microparticles (8 h) in
      duodenal and jejunum regions of intestine (F1, 1:2 ratio of CP:EC). Therefore, it
      may be concluded that drug loaded gastric-mucoadhesive microparticles are a
      suitable delivery system for metformin hydrochloride, and may be used for
      effective management of NIDDM (Non Insulin Dependent Diabetes Mellitus). 

PMID- 24734056
TI  - Structure Optimization of Neuraminidase Inhibitors as Potential Anti-Influenza
      (H1N1Inhibitors) Agents Using QSAR and Molecular Docking Studies.
AB  - The urgent need of neuraminidase inhibitors (NI) has provided an impetus for
      understanding the structure requisite at molecular level. Our search for
      selective inhibitors of neuraminidase has led to the identification of
      pharmacophoric requirements at various positions around acyl thiourea
      pharmacophore. The main objective of present study is to develop selective NI,
      with least toxicity and drug like ADMET properties. Electronic, Steric
      requirements were defined using kohnone nearest neighbour- molecular field
      analysis (kNN-MFA) model of 3D-QSAR studies. Results generated by QSAR studies
      showed that model has good internal as well as external predictivity. Such
      defined requirements were used to generate new chemical entities which exhibit
      higher promising predicted activities. To check selective binding of designed
      NCE's docking studies were carried out using the crystal structure of the
      neuraminidase enzyme having co-crystallized ligand Oseltamivir. Thus, molecular
      modelling provided a good platform to optimize the acyl thiourea pharmacophore
      for designing its derivatives having potent anti-viral activity. 

PMID- 24734058
TI  - Validated spectrophtometric method for determination of tamsulosin in bulk and
      pharmaceutical dosage forms.
AB  - In this study a sensitive, simple and accurate spectrophotometric method was
      suggested for determination of tamsulosin in bulk powder and pharmaceutical
      dosage form based on the formation of an ion-pair complex between the drug and
      bromocresol green in a buffer solution at pH 3.5. The formed yellow color complex
      was extracted with chloroform and measured at 415 nm. The optimum reaction
      conditions such as pH, reagent amount, extracting solvent and the stoichiometry
      of the ion-pair complex were investigated. Under the optimized conditions, the
      Beer's law was obeyed in the concentration range of 1-160 g/mL with acceptable
      correlation coefficient (r(2) > 0.9997) and precision (CV < 3%) and accuracy
      (error < 2%). The proposed method was successfully used for the determination of
      tamsulosin in pharmaceutical capsule with nosignificant interferences of
      excipients. 

PMID- 24734059
TI  - Synthesis of brominated 2-phenitidine derivatives as valuable inhibitors of
      cholinesterases for the treatment of Alzheimer's disease.
AB  - The present study reports the synthesis of a series N-substituted derivatives of
      brominated 2-phenitidine. First, the reaction of 2-phenitidine (1) with
      benzenesulfonyl chloride (2) in aqueous media yielded N-(2-ethoxyphenyl)
      benzenesulfonamide (3), which was then subjected to bromination with bromine in
      the presence of glacial acetic acid to give N-(4,5-dibromo-2-ethoxyphenyl)
      benzenesulfonamide (4). Secondly, the product (4) on further treatment with
      alkyl/aryl halides (5a-l) in the presence of lithium hydride (LiH) produced
      twelve new derivatives of N-substituted sulfonamides (6a-l). These were
      characterized by (1)H-NMR spectrum and screened against acetylcholinesterase
      (AChE), butyrylcholinesterase (BChE) and lipoxygenase (LOX) and were found to be
      valuable inhibitors of butyrylcholinesterase (BChE) and acetylcholinesterase
      (AChE). Few of them were also active against LOX. 

PMID- 24734060
TI  - Simple Synthesis and Biological Evaluation of Some Benzimidazoles Using Sodium
      Hexafluroaluminate, Na 3 AlF 6 , as an Efficient Catalyst.
AB  - Considerable attention has been focused on the synthesis of benzimidazoles due to
      having a broad spectrum of biological activities such as anti-parasitic,
      fungicidal, anti-thelemintic and anti-inflammatory activities. As a part of our
      research work in this area, a series of benzimidasole derivatives (3a-n) were
      synthesized in good to high yields by reaction of o-phenylenediamine and
      different aromatic aldehydes in the presence of sodium hexafluroaluminate,
      Na3AlF6, as an efficient catalyst at 50 (?)C. This environmentally benign and
      practical method offers several advantages, such as high yields, use of available
      catalyst, mild reaction conditions and easy workup. The antibacterial activity of
      these benzimidasoles was also evaluated using Staphylococcus aureus (mm) and
      Escherichia coli (mm) bacterial strain. All synthesized materials were
      characterized using IR and NMR spectroscopy as well as microanalyses data. 

PMID- 24734061
TI  - Oxidative Aromatization, Cytotoxic Activity Evaluation and Conformational Study
      of Novel 7-aryl-10, 11-dihydro-7H-chromeno [4, 3-b]quinoline-6, 8(9H, 12H)-dione
      Derivatives.
AB  - In the present work, novel 7-aryl-10, 11-dihydro-7H-chromeno [4, 3-b]quinoline-6,
      8(9H, 12H)-dione derivatives were synthesized by oxidation of 7-aryl-8, 9, 10, 12
      tetrahydro-7H-chromeno[4, 3-b]quinoline-6, 8-diones in the presence of silica
      sulfuric acid/NaNO2 with yields of 64-74%. Cytotoxic activity of synthesized
      compounds was assessed on three different human cancer cell lines (K562, LS180,
      and MCF-7). Synthesized compounds showed moderate cytotoxic activities. The most
      active one apeared to be 2e, containing a methoxy group on the meta position of
      phenyl ring (IC50 range in different cell lines: 11.1-55.7 uM). Furthermore;
      comparison of the cytotoxic activity of these novel oxidized derivatives with non
      oxidized counterparts revealed that oxidation of dihydropyridine ring to
      pyridine, improves the activity especially in LS180 cell line. Conformational
      analysis revealed that some conformational aspects of oxidized derivatives such
      as orientation of C7-aryl substitute were clearly different from non-oxidized
      ones. 

PMID- 24734062
TI  - Synthesis and evaluation of new fluorinated anti-tubercular compounds.
AB  - Treatment of tuberculosis (TB) and the discovery of effective new anti-tubercular
      drugs are among the most urgent priorities in health organizations all over the
      world. In the present study, fluorinated analogs of some of the most important
      anti-TB agents such as p-aminosalicylic acid (PAS), thiacetazone and pyrazinamide
      were synthesized and tested against TB. The fluorinated analog of thiacetazone
      was 20 times more potent than the parent compound against M.tuberculosis H37-RV,
      while the fluorinated p-aminosalicylic acid (PAS) was almost three times less
      potent than PAS. A few other halogenated analogs of thioacetazone were also
      synthesized and subjected to anti-M.tuberculosis screening tests. The best
      halogen substituent was found to be fluorine which has the smallest size from one
      hand and the strongest electronegativity from the other hand among the halogen
      atoms. Fluorine therefore could be considered as a golden substituent to improve
      the anti-M.tuberculosis activity of thioacetazone. 

PMID- 24734063
TI  - TLC-Bioautography and GC-MS Analyses for Detection and Identification of
      Antioxidant Constituents of Trachyspermum copticum Essential Oil.
AB  - The present work was designed to study the antioxidant activity and to identify
      the main active components of the essential oil of ajowan (Trachyspermum
      copticum) fruit. GC and GC-MS analyses of the essential oil showed the presence
      of eight compounds. The main constituents of the oil were thymol (43.7%), p
      cymene (26.8%), and gamma-terpinene (24.9%). The antioxidant and free radical
      scavenging activities of ajowan oil was evaluated by using ABTS(*+) and beta
      carotene bleaching assays. The oil exhibited a considerable dose-dependent
      antioxidant activity. Antioxidant activity guided fractionation of the oil was
      carried out by TLC-bioautography method based on the DPPH(*) assay to screen and
      separate the main active constituents. The bioautography screening and
      fractionation resulted in the separation of the main antioxidant compound which
      was identified as thymol. 

PMID- 24734064
TI  - Cycloartane Triterpenoids from Euphorbia Macrostegia with their Cytotoxicity
      against MDA-MB48 and MCF-7 Cancer Cell Lines.
AB  - The dried plant was extracted with dichloromethane and after defatting with
      hexane, transferred repeatedly on silica columns using dichloromethane-hexane and
      ethyl acetate-hexane as mobile phases. Finally the fractions were purified by
      high performance liquid chromatography using a Pack-Sil column and hexane: Ethyl
      acetate as mobile phase. The structures of the isolated compounds included:
      cycloart-25-ene-3beta, 24-diol (1), cycloart-23(Z)-ene-3beta, 25-diol (2),
      cycloart-23(E)-ene-3beta, 25-diol (3), and 24-methylene-cycloart-3beta-ol (4)
      were elucidated by (13)C- and (1)H-NMR as well as IR and by the aid of mass
      fragmentation pattern and comparing with the literature. The biological effects
      of the compounds were done by the MTT assay on two different cancer cell lines
      including MDA-MB48 and MCF-7. Among these compounds, cycloart-23(E)-ene-3beta,25
      diol (3) was the most active compound on MDA-MB468 cell line (LD50 = 2.05 MUgmL(-
      1) ) and cycloart-23(Z)-ene-3beta, 25-diol (2) was the most active compound on
      MCF-7 cell line (LD50 = 5.4 MUgmL(- 1)). 

PMID- 24734065
TI  - Isolation of aurantiamides from gomphrena celosioides C. Mart.
AB  - In West Africa and Nigeria in particular, many virgin plants are still waiting to
      be evaluated for their medicinal importance. Claims of plants with folk medicinal
      applications need to be evaluated and verified. Gomphrena celosioides (family -
      Amaranthaceae) is a weed grown in lawns and the biological activity of the
      extract had earlier been established. In the present study, the plant was
      collected, air dried, ground and soxhlet extracted with n-hexane and two
      compounds were isolated from the flakes that were recovered from the n-hexane
      extract on cooling. Column chromatography using 5% chloroform in n-hexane
      effected the separation. The structures of the isolated compounds were elucidated
      by spectroscopic analysis using IR, NMR ((1)H and (13)C) and EI-MS. The compounds
      were found to be aurantiamide and aurantiamide acetate. This is the first report
      of isolation of these compounds in Gomphrena celosioides. 

PMID- 24734066
TI  - Two matrix metalloproteinase inhibitors from scrophularia striata boiss.
AB  - Many species belonging to the Scrophularia genus have been used since ancient
      times as folk remedies for many medical conditions such as scrofulas, scabies,
      tumors, eczema, psoriasis, inflammations. The aim of this study was to
      characterize the matrix metalloproteinases (MMPs) inhibitor compounds of the
      Scrophularia striata extract by bio-guide fractionation. The aerial parts of S.
      striata were collected and different extracts were sequentially prepared with
      increasingly polar solvents. The MMPs inhibitory activity of the crude extract
      and its fractions were evaluated by the Zymoanalysis method. The pure compounds
      were purified from the active fraction by chromatography methods. Chemical
      structures were deduced by nuclear magnetic resonance and mass spectrometry. Two
      active compounds (acteoside and nepitrin) were identified by bio-guide
      fractionation. The inhibitory effects of nepitrin and acteoside at 20 ug/mL were
      about 56 and 18 percent, respectivly. The inhibitory effects of acteoside at 80
      ug/mL were increased to about 73 percent. In summary, the results suggest that
      nepitrin effectively inhibited MMPs inhibitory activity at low concentrations,
      whereas acteoside showed inhibition at high concentrations. 

PMID- 24734067
TI  - Ethno-medicinal plants used to cure jaundice by traditional healers of mashhad,
      iran.
AB  - Jaundice is the commonest ailments affecting the citizens of both developed and
      poor Asians countries including Iran. An ethnobotanical survey of plants used by
      the traditional healers for the treatment of jaundice was conducted in the
      Mashhad city, Northeastern Iran. A total of 37 plants belonging to 32 genera and
      26 families have been documented for their therapeutic use against jaundice. The
      plant families which contained the most commonly used species for their effects
      are: Fabaceae (5 species), Polygonaceae (4 sp.), Asteraceae (3 sp.),
      Plantaginaceae (2 sp.) and Salicaceae (2 sp.). The plants were arranged with
      correct nomenclature along with their common name, family, the part used and
      their medicinal value. The use of decoction is the most preferred method of
      herbal preparation. In all cases, the treatment involved oral administration of
      the extracts 2 to 3 times daily from a week to month till the problem disappears.
      Cichorium intybus, Salix alba, Cotoneaster nummularius, Descurainia sophia, Malva
      sylvestris, Berberis integrrima, Rumex acetosella, Phyllanthus emblica and Alhagi
      maurorum were repeatedly mentioned by the traditional healers as the most widely
      used for the treatment of jaundice in the study area. The study indicates that
      the local inhabitants rely on medicinal plants for treatment. This paper
      suggested that further clinical experimentation is needed to scientifically
      evaluate these widely used herbal remedies for possible bioactive effects. 

PMID- 24734068
TI  - Antioxidant Activity, Total Phenolics and Flavonoid Contents of some Edible Green
      Seaweeds from Northern Coasts of the Persian Gulf.
AB  - The antioxidant activity, contents of total phenolics and flavonoids were
      quantified in the methanolic extracts of four Ulva species (Ulva clathrata (Roth)
      C.Agardh, Ulva linza Linnaeus, Ulva flexuosa Wulfen and Ulva intestinalis
      Linnaeus) grown at different parts of northern coasts of the Persian Gulf in
      south of Iran. The seaweeds were collected from Dayyer, Taheri and Northern Ouli
      coasts in April 2011. Methanolic extracts of the seaweeds were assessed for their
      antioxidant activity using DPPH radical scavenging assay and was performed in a
      microplate reader. All species exhibited a DPPH radical scavenging activity, and
      among the species, Ulva clathrata demonstrated greater antioxidant potential with
      a low IC50 (0.881 mg mL(-1)) in comparison with those of the other species. Also
      the highest phenolic content (5.080 mg GAE g(-1)) and flavonoid content (33.094
      mg RE g(-1)) were observed in U.clathrata. Total phenolic and flavonoid contents
      showed positive correlations with the DPPH radical scavenging activity (p < 0.01)
      and negative correlations with IC50 (p < 0.01).The results suggest that these
      edible green seaweeds possess antioxidant potential which could be considered for
      future applications in medicine, dietary supplements ,cosmetics or food
      industries. 

PMID- 24734069
TI  - Identification of a Novel Antibiotic from Myxobacterium Stigmatella Eracta WXNXJ
      B and Evaluation of its Antitumor Effects I n - vitro.
AB  - This work was to isolate and identify the bioactive secondary metabolite which
      was produced by myxobacterium Stigmatella eracta WXNXJ-B, and to evaluate its
      antitumor and apoptosis-inducing effects. The results showed that one novel
      compound (molecular formula C29H25NO3) was isolated, purified by Sephadex LH-20
      column chromatography and preparative RP-HPLC, and identified as 5-(6-benzyl
      quinolin-3-ylmethyl)-6- phenyl-3,7-dioxa- bicycle [4.1.0] heptan-3-one (named as
      quinoxalone) according to its UV, IR, HRMS and NMR spectra. The compound showed
      strong antitumor activity on B16, HepG2, MCF-7, SGC-7901, MDA-MB231 and CT-26 six
      tumor cell lines in-vitro. Nevertheless, it showed less cytotoxic to the mouse
      normal spleen cells (IC50 was 836.27 +/- 13.02 ug mL(-1)). The cytotoxic study on
      HepG2 cells in-vitro showed that quinoxalone could induce the change of cell
      nuclear and arrested the cell division in the S and G2/M phase. Our results
      suggest that quinoxalone could be a potential anti-cancer agent. 

PMID- 24734070
TI  - The Study of Pentoxifylline Drug Effects on Renal Apoptosis and BCL-2 Gene
      Expression Changes Following Ischemic Reperfusion Injury in Rat.
AB  - Ischemia Reperfusion injury is the tissue damage caused when blood supply returns
      to the tissue after a period of ischemia or lack of oxygen. In this study, the
      effect of pentoxyfylline on BCL-2 gene expression changes and cell injury in
      kidney of rat following Ischemia Reperfusion were evaluated. In this experimental
      study, 20 male wistar rats with average weight of 250-300 g were selected and
      then were accidently divided them on two tenth group of control and treatment
      groups. In the control group, celiotomy was performed by ventral midline
      incision. The left kidney was isolated, and then both the renal artery and vein
      were obstructed. After 60 minutes of warm ischemia, vessel obstruction resolved
      and the right kidney was removed. 72 hours after reperfusion, tissue samples were
      taken from left kidney for Tunel assay. We used quantitative real time PCR for
      detection of BCL-2 gene expression in treated groups and then compared them to
      control samples. In the treatment group, the cell death changes, showed lower
      level than the control group. The results also showed the BCL-2 gene expression
      was declined in ischemia group as campared to PNT drug group. The pentoxyfylline
      might have a role in control of apoptosis result from Ischemia- reperfusion and
      quantitative real-time PCR can be used as a direct method for detection BCL-2
      gene expression in tested samples and normal samples. 

PMID- 24734071
TI  - Cytochrome C and Caspase-3/7 are Involved in Mycophenolic Acid- Induced Apoptosis
      in Genetically Engineered PC12 Neuronal Cells Expressing the p53 gene.
AB  - Mycophenolic acid (MPA) is the active metabolite of mycophenolate mofetil. This
      study designed to investigate the mechanism of cytotoxicity of MPA on the
      genetically engineered PC12 Tet Off (PTO) neuronal cells with p53 gene. Alamar
      Blue (AB) reduction showed concentration-dependent cytotoxicity of MPA on PTO
      cells with IC50 value of 32.32 +/- 4.61 MUM. The reactive oxygen species (ROS)
      generation following exposing the cells to MPA showed a significant (p < 0.05)
      increase in the ROS production and in a concentration-dependent fashion.
      Involvement of Caspase 3/7 proteases and Cytochrome C release in the induction of
      DNA fragmentation are all hallmarks of MPA-induced apoptosis in PTO cells. Our
      data suggest that MPA exerts an apoptotic effect on PTO cells. Moreover, the
      apoptotic effect of MPA attribute to the elevation of ROS generation by which
      might trigger the cytochrome C release and the activation of Caspase 3/7 that
      ultimately results in DNA fragmentation. 

PMID- 24734072
TI  - Embryo toxic effects of depleted uranium on the morphology of the mouse fetus.
AB  - Although the biokinetics, metabolism, and chemical toxicity of uranium are well
      known, until recently little attention was paid to the potential toxic effects of
      uranium on reproduction and development in mammals. In recent years, it has been
      shown that uranium is a developmental toxicant when given orally or
      subcutaneously (SC) to mice. Decreased fertility, embryo/fetal toxicity including
      teratogenicity, and reduced growth of the offspring have been observed following
      uranium exposure at different gestation periods. For investigating the effects of
      DU on pregnant animals, three groups (control, sham and test) of NMRI mice were
      chosen. In test group 4 mg/Kg of DU were administered intraperitonealy at 11 day
      of gestation, in sham group only normal saline injected to interior peritoneum as
      indicated in the test group and in Control group which was considered as the
      comparison base line of our research, no injection was made. Caesarean sections
      were performed at 15 day of the gestation; and their placentas were examined
      externally. Base on our results DU caused significant external anomalies, and
      caused a significant decrease (p < 0.05) in the weight and diameter of placentas,
      the number of the embryos, their body weight and crown-rump length of fetuses. 

PMID- 24734074
TI  - Composition and Free Radical Scavenging Activity of Kernel Oil from Torreya
      grandis, Carya Cathayensis, and Myrica R ubra.
AB  - In this study, we measured the composition and free radical scavenging activity
      of several species of nuts, namely, Torreya grandis, Carya cathayensis, and
      Myrica rubra. The nut kernels of the aforementioned species are rich in fatty
      acids, particularly in unsaturated fatty acids, and have 51% oil content. T.
      grandis and C. cathayensis are mostly produced in ZheJiang province. The trace
      elements in the kernels of T. grandis and C. cathayensis were generally higher
      than those in M. rubra, except for Fe with a value of 64.41 mg/Kg. T. grandis is
      rich in selenium (52.91-68.71 mg/Kg). All three kernel oils have a certain free
      radical scavenging capacity, with the highest value in M. rubra. In the DPPH
      assay, the IC50 of M. rubra kernel oil was 60 MUg/mL, and OH was 100 MUg/mL. The
      results of this study provide basic data for the future development of the edible
      nut resources in ZheJiang province. 

PMID- 24734073
TI  - Antioxidant, Anti-inflammatory and Antiproliferative Effects of Aqueous Extracts
      of Three Mediterranean Brown Seaweeds of the Genus Cystoseira.
AB  - Seaweeds have caused an emerging interest in the biomedical area, mainly due to
      their contents of bioactive substances which show great potential as anti
      inflammatory, anti-microbial, anti-viral and anti-tumoral drugs. Despite the
      diversity in quality and quantity of the Mediterranean Tunisian coast flora, with
      its large contains of marine organisms and seaweeds, most of them have not yet
      been investigated for pharmacological and biological activities. Antioxidant,
      anti-inflammatory and antiproliferative effects of the aqueous extracts (AQ) of
      three brown seaweed respectively, Cystoseira crinita (AQ-C cri), Cystoseira
      sedoides (AQ-C sed) and Cystoseira compressa (AQ-C com) were investigated.
      Antioxidant activity was evaluated using the DPPH assay. Total phenolic contents
      were measured using Folin-Ciocalteu method. The anti-inflammatory activity of
      these extracts was determined in-vivo, using carrageenan induced rat paw oedema
      assay. The antiproliferative activity was studied on normal cells (MDCK and rat
      fibroblast) and cancer (A549, MCF7 and HCT15) cell lines by the ability of the
      cells to metabolically reduce MTT formazan dyes, in comparison to a reference
      drug the Cisplatin. Results demonstrated that AQ-C cri, AQ-C sed and AQ-C com
      extracts exhibited significant radical scavenging activity. AQ-C com extract had
      the highest total phenolic content. AQ-C cri, AQ-C sed and AQ-C com extracts
      exhibited significant anti-inflammatory activity in a dose dependent manner by
      comparison to reference drugs. Moreover, AQ-C cri, AQ-C sed and AQ-C com extracts
      showed an important antiproliferative activity against both Human tumor cell
      lines HCT15 and MCF7. These pharmacological efficacies of these AQ- extracts of
      Cystoseira were positively correlated with their total phenol content and their
      good antioxidant activity. The purification and the determination of chemical
      structures of compounds of these active aqueous extracts are under investigation.
      It could have a promising role in the future medicine and nutrition when used as
      drug or food additive. 

PMID- 24734075
TI  - Neuroprotective effect of thymoquinone, the nigella sativa bioactive compound, in
      6-hydroxydopamine-induced hemi-parkinsonian rat model.
AB  - Parkinson disease (PD) is the most common movement disorder with progressive
      degeneration of midbrain dopaminergic neurons for which current treatments afford
      symptomatic relief with no-prevention of disease progression. Due to the
      neuroprotective property of the Nigella sativa bioactive compound thymoquinone
      (TQ), this study was undertaken to evaluate whether TQ could improve behavioral
      and cellular abnormalities and markers of oxidative stress in an experimental
      model of early PD in rat. Unilateral intrastriatal 6-hydroxydopamine (6-OHDA)
      lesioned rats were daily pretreated p.o. with TQ at doses of 5 and/or 10 mg/Kg
      three times at an interval of 24 h. After 1 week, apomorphine caused
      contralateral rotations, a reduction in the number of neurons on the left side of
      the substantia nigra pars compacta (SNC) was observed, malondialdehyde (MDA) and
      nitrite level in midbrain homogenate increased and activity of superoxide
      dismutase (SOD) reduced in the 6-OHDA lesion group. TQ pretreatment significantly
      improved turning behavior, prevented loss of SNC neurons, and lowered level of
      MDA. These results suggest that TQ could afford neuroprotection against 6-OHDA
      neurotoxicity that is partly due to the attenuation of lipid peroxidation and
      this may provide benefits, along with other therapies, in neurodegenerative
      disorders including PD. 

PMID- 24734076
TI  - Toxicity Effect of Silver Nanoparticles on Mice Liver Primary Cell Culture and
      HepG2 Cell Line.
AB  - Nano-silver (AgNP) has biological properties which are significant for consumer
      products, food technology, textiles and medical applications (e.g. wound care
      products, implantable medical devices, in diagnosis, drug delivery, and imaging).
      For their antibacterial activity, silver nanoparticles are largely used in
      various commercially available products. Thus, the use of nano-silver is becoming
      more and more widespread in medicine. In this study we investigated the cytotoxic
      effects of AgNPs on liver primary cells of mice, as well as the human liver HepG2
      cell. Cell viability was examined with MTT assay after HepG2 cells exposure to
      AgNPs at 1, 2, 3, 4, 5, 7.5, 10 ppm compared to mice primary liver cells at 1,
      10, 50, 100, 150, 200, 400 ppm for 24h. AgNPs caused a concentration-dependent
      decrease of cell viability in both cells. IC50 value of 2.764 ppm (ug/mL) was
      calculated in HepG2 cell line and IC50 value of 121.7 ppm (ug/mL) was calculated
      in primary liver cells of mice. The results of this experiment indicated that
      silver nanoparticles had cytotoxic effects on HepG2 cell line and primary liver
      cells of mice. The results illustrated that nano-silver had 44 times stronger
      inhibitory effect on the growth of cancerous cells (HepG2 cell line) compared to
      the normal cells (primary liver cells of mice). which might further justify AgNPs
      as a cytotoxic agents and a potential anticancer candidate which needs further
      studies in this regard. 

PMID- 24734077
TI  - Effects of minoxidil gel on burn wound healing in rats.
AB  - Minoxidil has been reported to inhibit in-vitro fibroblast proliferation and
      lysyl hydroxylase activity, a key enzyme in collagen biosynthesis. These in-vitro
      effects proposed minoxidil to be a potential antifibrotic agent. The present
      study aimed to investigate the effects of minoxidil gel on wound healing
      procedure in a second-degree burn model in rats. Wistar rats were anesthetized
      and a second-degree burn was induced on the back of Wistar rats using a heated 2
      cm diameter metal plate. Experimental groups received 2% or 5% topical minoxidil
      gel, dexpanthenol or sliver sulfadiazine. Histological parameters including
      collagen content, angiogenesis, number of preserved follicles and necrosis along
      with tensile strength of burn wound area were assessed on days 3, 7, 14 and 21
      post-injury.Microscopic evaluation of specimens collected from sample animals
      were consistent and showed a second-degree burn. Main histological findings
      regarding minoxidil topical usage showed that collagen content and tensile
      strength of burned area did not differ between groups. However, minoxidil
      increased the number and diameter of blood vessels significantly compared with
      other groups.Although minoxidil improved the process of wound-healing, our
      results did not support the proposed idea of its usage as an antifibrotic agent.
      However, to reject its possible effects as an antifibrotic agent, more objective
      animal models should be developed and studied. 

PMID- 24734079
TI  - Topical simvastatin enhances tissue regeneration in full-thickness skin wounds in
      rat models.
AB  - Wounds and wound healing have always been one of the most important subjects that
      experimental researches were dedicated to. Simvastatin has been used for long as
      a common lipid lowering agent which was reported to have some pleiotropic effects
      such as antioxidation, anti-inflammation and immunomodulation. In this study we
      aimed to determine the effect of simvastatin on wound healing process in
      laboratory rats by means of stereological and histopathological analyses. 36 male
      Sprague-Dawley rats (220 +/- 20 g) with a 1 cm(2) circular full-thickness wound
      on their back were divided into three groups: SS group that received a gel with
      2% concentration of simvastatin; UW group that received no treatment but daily
      irrigation with normal saline; Base group that was treated with the gel base.
      Duration of the study was 12 days and at the end, wound closure rate, grade of
      inflammation, granulation-tissue formation, ulceration, epithelization,
      fibroblast proliferation, collagen-bundles synthesis, and vascularization were
      determined. Outcome of this study revealed that Simvastatin improves the wound
      healing by its anti-inflammatory and epithelization induction effect as well as
      statistically significant induction of fibroblast proliferation and collagen
      bundle synthesis which were reported by our stereological and histopathological
      investigations. Results of the present study demonstrated that topical
      Simvastatin enhances the wound healing process through affecting different
      aspects of tissue regeneration; however, further researches are needed to find
      the exact mechanism, advantages and disadvantages of this chemical agent. 

PMID- 24734078
TI  - Propofol Attenuates Toxic Oxidative Stress by CCl4 in Liver Mitochondria and
      Blood in Rat.
AB  - Anti-oxidant effects of propofol (2, 6-diisopropylphenol) were evaluated agains
      carbon tetrachloridet CCl4 -induced oxidative stress in rat liver. 30 male rats
      were equally divided in to 6 groups (5 rats each). Group I (control), while Group
      II was given CCl4 (3 mL /Kg/day, IP). Animals of Groups III received only
      propofol (10 mg/Kg/day, IP). Group IV was given propofol+ CCl4. Group V was
      administered vitamin E (alpha-tocopherol acetate 15 mg/Kg/day, SC) .Animals of
      Group VII received alpha-tocopherol acetate + CCl4 once daily for two weeks.
      After treatment, blood and liver mitochondria were isolated. Anti-oxidant enzymes
      activity such as glutathione peroxidase (GPx), superoxide dismutase (SOD) and
      oxidative stress marker such as reduced glutathione (GSH) and lipid peroxidation
      (LPO) concentration were measured. Oxidative stress induced with CCl4 in liver
      mitochondria was evident by a significant increase in enzymatic activities of
      GPx, SOD, and LPO and decreased of GSH and vailability of mitochondria. Propofol
      and vitamin E restored CCl4-induced changes in GSH, GPx, SOD and LPO in blood and
      liver mitochondria. CCl4 decreased viability of mitochondria that was recovered
      by propofol and vitamin E. It is concluded that oxidative damage is the mechanism
      of toxicity of CCl4 in the mitochondria that can be recovered by propofol
      comparable to vitamin E. 

PMID- 24734080
TI  - Costs of Treatment after Renal Transplantation: Is it Worth to Pay More?
AB  - The primary aim of the study was to estimate costs of treatment for the first
      year after renal transplantation from the perspective of health insurance
      organizations in Iran. An Excel-based and a Monte Carlo model were developed to
      determine the treatment costs of current clinical practice in renal
      transplantation therapy (RTT). Inputs were derived from Ministry of Health and
      insurance organizations database, hospital and pharmacy records, clinical trials
      and local and international literature. According to the model, there were almost
      17,000 patients receiving RTT in Iran, out of which about 2,200 patients
      underwent the operation within the study year (2011 - 2012; n = 2,200) The
      estimated first year total treatment cost after renal transplantation was almost
      $14,000,000. These costs corresponded to annual total cost per patient of almost
      $6500 for the payers. Renal transplantation therapy is almost fully reimbursed by
      government in Iran. However, regarding new expensive medicines, cost of medical
      expenditure is rapidly growing and becoming quite unaffordable for the
      government; therefore, out-of-pocket (OOP) payments are dramatically increasing
      over time. In order to improve reimbursement policy making under pressure of
      current budget constraints, the present study is providing decision makers with
      practical tools make it possible for them to easily compare budgetary impact of
      the current therapy strategy with the future financial consequences of purchasing
      newly proposed medicines. In other words having estimation of the current budget
      spending on RTT would help policy makers in making efficient resource allocation
      and decrease quite high OOP expenditures. 

PMID- 24734081
TI  - Clinical pharmacokinetics of tacrolimus in Iranian liver transplant recipients.
AB  - Tacrolimus, a cornerstone of immunosuppressive therapy in solid organ
      transplantation, has a narrow therapeutic range with considerable inter
      individual and intra-individual pharmacokinetic variability. To date, there is no
      information on the pharmacokinetics of tacrolimus in Iranian liver transplant
      recipients. This study was designed to determine pharmacokinetic properties of
      orally administered tacrolimus in Iranian adult liver transplant recipients.
      Tacrolimus doses and steady state whole blood trough concentrations as well as
      patient demographic and clinical data were obtained retrospectively using the 30
      included patients' medical records. Pharmacokinetic parameters were estimated by
      using a nonlinear mixed effect model program (Monolix version 3.1). Absorption
      rate constant was fixed at two hours(-1). Drug apparent clearance (CL/F),
      apparent volume of distribution (Vd/F), and elimination half life (t1/2beta) were
      calculated. The administered dose of tacrolimus to the patients ranged from 0.02
      to 0.14 mg/Kg/day. Tacrolimus blood trough concentrations varied widely within
      the range of 1.8 to 30 ng/mL. The mean values of CL/F, Vd/F, and t1/2beta were
      found to be 9.3 +/- 0.96 L/h, 101 +/- 29 L, and 7.5 hours, respectively. The
      pharmacokinetics of tacrolimus was highly variable among our patients. CL/F,
      Vd/F, and t1/2beta of tacrolimus in this study were comparable to reported values
      from Italian heart transplant patients but somewhat different from reported ones
      from other solid organ transplant populations. 

PMID- 24734082
TI  - Dosage comparison of snake anti-venomon coagulopathy.
AB  - This study was done to determine whether high or low dose ofanti-snake venom
      (ASV) is better incoagulopathy invictims of envenoming by vipers. This
      retrospective study was conducted on the 154 patients (Mean age +/- SD, Range) of
      viper snake bites who were referred to the emergency ward of Razi Hospital,
      Ahvaz, Iran over 2 years period (2004-2006).According to the treatment dosage the
      patients were divided in two groups include group 1(78 cases), low dose regimen
      and group 2 (76 cases), high dose one. In group 1, the treatment was performed by
      administration of 4 to 6 vials of ASV through intravenous infusion.In group 2,
      the patients were given 5 to 10 vials of ASV as an initial dose. In low dose
      regimen, the number of received packed red blood cell was higher (14 vs. 3) in
      comparison with high dose group. The number of ASV vials the patients received
      was 5.5and 21.06 in group 1 and 2, respectively (5.5+/-1.7 vs. 21.06+/-10.89; p <
      0.01).The difference in frequency of coagulopathy complications, and need for
      using packed red blood cell were statistically significant(96.2% and 17.9% in
      group 1 vs. 34.2% and 3.9% in group 2, p < 0.01).It seems that cautious usage of
      high dose of ASV (10-20 vials) without very special concerns about the cost,
      dose, and without hazardous side effects is essential for the routine management
      of sever snake envenoming. 

PMID- 24734083
TI  - Increasing the number of adverse drug reactions reporting: the role of clinical
      pharmacy residents.
AB  - Detection of adverse drug reactions (ADRs) in hospitals provides an important
      measure of the burden of drug related morbidity on the healthcare system.
      Spontaneous reporting of ADRs is scare and several obstacles to such reporting
      have been identified formerly. This study aimed to determine the role of clinical
      pharmacy residents in ADR reporting within a hospital setting. Clinical pharmacy
      residents were trained to report all suspected ADRs through ADR-reporting yellow
      cards. The incidence, pattern, seriousness, and preventability of the reported
      ADRs were analyzed. During the period of 12 months, for 8559 patients, 202 ADR
      reports were received. The most frequently reported reactions were due to anti
      infective agents (38.38%). Rifampin accounted for the highest number of the
      reported ADRs among anti-infective agents. The gastro-intestinal system was the
      most frequently affected system (21.56%) of all reactions. Fifty four of the ADRs
      were reported as serious reactions. Eighteen of the ADRs were classified as
      preventable. Clinical pharmacy residents' involvement in the ADR reporting
      program could improve the ADR reporting system. 

PMID- 24734084
TI  - Vaginal versus sublingual misoprostol for labor induction at term and post term:
      a randomized prospective study.
AB  - We want to compare the efficacy and safety of vaginal versus sublingual
      misoprostol for cervical ripening and induction of labor. This randomized
      clinical trial was performed on 140 women with medical or obstetric indications
      for labor induction. The patients were randomly divided into two groups: vaginal
      and sublingual administration of misoprostol. In first group, 25 ug misoprostol
      was placed in the posterior fornix of the vagina and second group received 25 ug
      misoprostol sublingually, every 6 hours for 24 h. Maternal and neonatal outcomes
      were analyzed. There was no significant difference in the demographic
      characteristics between two groups. The main indication for cesarean section in
      both groups was fetal distress, followed by absence of active labor progress.
      Evaluation of cesarean indication was not significantly different in two groups;
      including fetal distress, absence of active labor, uterine over activity and
      failure to progress. The maternal complication in sublingual group included
      residual placenta (2%), tachysystole (2%), vomiting (12%), atoni (3.3%) and
      abdominal pain (5.5%), although there was no significant difference between two
      groups. Sublingual misoprostol is as effective as vaginal misoprostol for
      induction of labor at term. However, sublingual misoprostol has the advantage of
      easy administration and may be more suitable than vaginal misoprostol. 

PMID- 24734085
TI  - Assessment of cyclosporine serum concentrations on the incidence of acute graft
      versus host disease post hematopoietic stem cell transplantation.
AB  - Allogeneic hematopoietic stem cell transplantation (HSCT) is a curative treatment
      option for hematological disorders. Cyclosporine (CsA) is one of the major
      immunosuppressive agents for the prophylaxis against graft versus host disease
      (GvHD). In this retrospective study, we evaluated the effects of CsA serum levels
      on the incidence of acute GvHD and transplant outcomes. Retrospective study in
      103 adult patients received Hematopoitic Stem Cell Transplantation (HSCT) in the
      Hematology-Oncology, Bone Marrow Transplantation center at Shariati Hospital in
      Tehran, Iran. All participants received prophylactic regimen of cyclosporine plus
      methotrexate. CsA dose titration was done according to patients? serum levels and
      drug toxicity. Serum levels tested on the twice weekly basis in first 4 weeks
      after transplantation. Acute GvHD (grades II-IV) developed in 44 patients (43%,
      95%CI: 33%-52%). The median time to ANC and PLT recovery was 13 days (range: 9-31
      days) and 16 days (range: 0-38 days), respectively. Univariate analysis of risk
      factors related to aGvHD (grade II-IV) development showed a higher risk of
      incidence of aGvHD (grades II-IV) for patients having the lowest blood CSA
      concentration (<200 ng/mL) in the third weeks after transplantation (36% vs. 12%,
      P = 0.035). The only risk factors related to incidence of aGvHD grades III-IV was
      also blood CsA concentration at 3(rd) week post-transplant (15% vs. 3%, P =
      0.047). The CsA concentration at 3(rd) week was not related to disease free
      survival and overall survival (P = 0.913 vs. P = 0.81) respectively. Higher CsA
      serum levels in the third week post HSCT significantly decreased incidence of
      acute GvHD. 

PMID- 24734086
TI  - Correlation between Cigarette Smoking and Urine Cotinine Level in Gastric Cancer
      Patients.
AB  - Various substances in cigarette smoke including nicotine have been shown to
      promote/induce cancer cell proliferation. Since cotinine has a longer half life
      and stability in the blood, it has become the preferred biomarker for cigarette
      smoking exposure. Seventy-three gastric cancer patients were included in this
      study. The tumor tissues were stained with H & E for pathological evaluation. The
      cotinine levels were measured in urine using a competitive ELISA. Tumors were 90%
      adenocarcinoma with 63% intestinal and 37% diffuse subtypes. Tumors were poorly
      (45.2%) or moderately differentiated (41.1%) and localized mainly (77%) in the
      upper part of stomach. The levels of cotinine were significantly different
      between smoker (283.83 +/- 178.10 ng/mL) and non-smoker (39.28 +/- 113.34 ng/mL)
      groups (p < 0.001). However, there is no-significant correlation between tumor
      characteristics and cotinine level in smoker patients. Cotinine level correlates
      with smoking in gastric patients, however, correlation with the tumor features
      has not been observed. 

PMID- 24734087
TI  - Plasma Vitamin D Status and Its Correlation with Risk Factors of Thrombosis, P
      selectin and hs-CRP Level in Patients with Venous Thromboembolism; the First
      Study of Iranian Population.
AB  - Low plasma level of vitamin D is linked to the increased risk of cardiovascular
      diseases such as hypertension, diabetes, dyslipidemia and peripheral vascular
      diseases. Vitamin D deficiency is a worldwide problem that involves Iranian
      population. To the best of our knowledge, this was the first investigation on
      venous thromboembolism (VTE) subjects that assessed the correlation of vitamin D
      level with plasma P-selectin, hs-CRP, and risk factors of thrombosis. In this
      prospective pilot study, patients with diagnosis of acute deep vein thrombosis
      and/ or pulmonary embolism were enrolled. All patients' clinical data,
      demographics and risk factors of thrombosis were evaluated. Plasma level of P
      selectin and hs-CRP were measured by ELISA method. Radio immune assay method was
      used to determine plasma level of 25-hydroxy vitamin D (25(OH) D). In this study,
      60 subjects were included. The mean +/- SD plasma 25-hydroxy vitamin D level
      (25(OH) D) of participants was 21.4 +/- 14.6 ng/mL. The vitamin D deficiency was
      detected in 60% of patients. No significant relation was found between the plasma
      25(OH)D level and P-selectin and hs-CRP. In multiple regression analysis, there
      was a significant relationship between the level of 25(OH)D and the patients' age
      (beta = 0.452; p = 0.001), diabetes (beta = 0.280; p = 0.036) and positive family
      history of cardiovascular diseases (beta = 0.373; p = 0.003). Vitamin D
      deficiency is a frequent problem in Iranian VTE patients. Moreover, Plasma level
      of vitamin D is not associated with P-selectin and hs-CRP in VTE patients. 

PMID- 24734088
TI  - Effects of ethanol on the toxicokinetics of methamphetamine in rabbits.
AB  - In the current study, the effects of ethanol (EtOH) on toxicokinetics of
      methamphetamine (MA) and its metabolite amphetamine (AP) were investigated. A
      single dose of MA hydrochloride at 15 mg/Kg was given intragastrically, either
      alone (MA group; n = 8) or in conjunction with 3 g/Kg EtOH (MA+EtOH group; n = 8)
      to rabbits. In placebo group, normal saline only was given (placebo group; n =
      4). Plasma and urine samples were collected and analyzed by gas
      chromatography/mass spectrometry (GC/MS) for MA and AP. Toxicokinetic parameters
      of MA and AP were determined using WinNonlin. Our results showed that
      toxicokinetic profiles of MA and AP in the two experimental groups were both
      fitted to an open two-compartment model with first-order kinetics. These were not
      affected by co-administration of EtOH. However, concomitant intake of EtOH
      significantly increased MA plasma absorption constant (Ka) and maximum
      concentration (Cmax). The Ka of MA was increased from 0.679/h +/- 0.023/h to
      0.964/h +/- 0.033/h (P < 0.05, the mean Cmax from 1.408 mg/L +/- 0.072 mg/L to
      1.676 mg/L +/- 0.135 mg/L (P < 0.05), whereas the Tmax was significantly
      decreased from 1.620 h +/- 0.062 h to 1.259h +/- 0.033h (P < 0.05). In contrast,
      no significant difference was observed on MA elimination. Furthermore, the plasma
      AP area under the curve (AUC0-30 h) increased from 5.281 mg/h/L +/- 0.264 mg/h/L
      to.13.052 mg/h/L +/- 0.956 mg/h/L and Cmax increased from 0.315 mg/L +/- 0.010
      mg/L to 0.423 mg/L +/- 0.042 mg/L (P < 0.01). Taken together, co-administration
      of EtOH with MA significantly accelerated MA absorption and subsequent metabolism
      to AP, but did not have significant effect on MA elimination. 

PMID- 24734089
TI  - Component analysis of Iranian crack; a newly abused narcotic substance in iran.
AB  - Iranian crack is a new form of narcotic substance that has found widespread
      prevalence in Iran in the past years. Crack only nominally resembles crack
      cocaine as it is widely different in its clinical signs. Thus the present study
      aims to quantify the chemical combination of this drug. The samples included 18
      specimen of Crack collected from different zones of Tehran, Iran. All specimens
      were in the form of inodorous cream solid powdery substance. TLC and HPLC methods
      were used to perform semi-quantitative and quantitative analysis of the
      components, respectively. The TLC analysis showed no cocaine compound in the
      specimens while they all revealed to contain heroin, codeine, morphine and
      caffeine. All but two specimens contained thebaine. None of the specimens
      contained amphetamine, benzodiazepines, tricyclic antidepressants, aspirin,
      barbiturates, tramadol and buprenorphine. Acetaminophen was found in four
      specimens. HPLC revealed heroin to be the foundation substance in all specimens
      and most of them contained a significant amount of acetylcodeine. The present
      analysis of the chemical combination of Crack showed that this substance is a
      heroin-based narcotic which is basically different from the cocaine-based crack
      used in Western countries. Studies like the present one at different time points,
      especially when abnormal clinical signs are detected, can reveal the chemical
      combination of the target substance and contribute to the clinical management of
      its acute or chronic poisoning. 

PMID- 24734090
TI  - Simultaneous Measurement of Zinc, Copper, Lead and Cadmium in Baby Weaning Food
      and Powder Milk by DPASV.
AB  - Apart from the breast milk, infant formula and baby weaning food have a special
      role in infant diet. Infants and young children are very susceptible to amount of
      trace elements. Copper and zinc are two elements that add in infant food. Lead
      and cadmium are heavy metals that enter to food chain unavoidably. DPASV is a
      benefit and applicable method for measurement of trace elements in food products.
      In this study, concentration of zinc, copper, lead and cadmium in four brands of
      baby food (rice and wheat based) and powder milk was analyzed with DPASV and
      polarograph set. Total Mean +/- SE of zinc, copper, lead and cadmium in baby
      foods (n = 240) were 11.86 +/- 1.474 mg/100g, 508.197 +/- 83.154 MUg/100g, 0.445
      +/- 0.006, 0.050 +/- 0.005 mg/Kg respectively. Also these amount in powder milk
      (n = 240) were 3.621+/- 0.529 mg/100g, 403.822 +/- 133.953 MUg/100g, 0.007 +/-
      0.003, 0.060 +/- 0.040 mg/Kg respectively. Zinc level in baby food type I was
      higher than lablled value (P = 0.030), but in other brands was not difference.
      Concentration of copper in all of samples was in labeled range (P > 0.05). In
      each four products, level of lead and cadmium were lower than the standard limit
      (P < 0.05). Amount of zinc and lead in baby food I, had difference versus other
      products. Concentration of zinc, camium in baby food type I, was higher than type
      II (P = 0.043, 0.001 respectively). Concentration of lead and cadmium in baby
      food type II, was higher than infant formulas, but are in standard limit. 

PMID- 24734091
TI  - The IFN-lambda Genetic Polymorphism Association With the Viral Clearance Induced
      by Hepatitis C Virus Treatment in Pakistani Patients.
AB  - BACKGROUND: Polymorphisms in the interferon lambda (INF lambda) genes on
      chromosome 19 have been associated with clearance of hepatitis C virus (HCV)
      induced by interferon and ribavirin therapy however there is no such data
      available for Pakistani patients with HCV infection. OBJECTIVES: In this study,
      the effects of single nucleotide polymorphisms (SNPs) have been investigated in
      response to treatment with interferon-alpha and ribavirin in a cohort of 75 HCV
      genotype 3a patients. PATIENTS AND METHODS: A total number of 50 SNPs from the
      Interferon lambda region on chromosome 19 were genotyped to investigate allelic
      associations with the treatment response in HCV type 3a patients. Thirteen SNPs
      were associated with HCV clearance, with the most significant alleles being
      RS8109886 (Fisher's P = 0.0001), RS8113007 (Fisher's P = 0.0001) and RS12979860
      (Fisher's P = 0.0002). RESULTS: These SNPs were found to be the most suitable
      SNPs for predicting treatment response in the present study. These findings
      support those reported previously. This could be used to improve HCV treatment
      strategies and suggest that Pakistani patients should be genotyped for the
      relevant SNPs to identify the patients who are more likely to respond to
      interferon and ribavirin therapy. CONCLUSIONS: This therapy is costly and can be
      accompanied by several adverse side-effects, hence pre-treatment prediction of
      patients who are most likely to benefit would have both economic and patient
      benefits in the long term.

PMID- 24734092
TI  - Mysterious Linkages Between Hepatitis C Virus Genotypes, Interleukin-28B
      Genotypes and Viral Clearance- A Meta-Analysis.
AB  - BACKGROUND: Recent genome wide association studies (GWAS) have shown important
      roles of single nucleotide polymorphisms (SNP) near region of interleukin B 28
      (IL28B) gene in spontaneous and drug-induced clearance of hepatitis C virus (HCV)
      in genotype 1 HCV infection. OBJECTIVES: This meta-analysis was designed to
      determine the world-wide distribution patterns of IL28B genotypes and alleles,
      and to find possible linkages between IL28B and HCV genotypes. PATIENTS AND
      METHODS: Manual and electronic databases were searched. Critical appraisal was
      performed. According to the results of heterogeneity tests, we used fix/random
      model for the analysis. The data concerning patients' ethnicity and HCV genotypes
      were analyzed by using statistical analysis software. RESULTS: A total of 255
      articles were found. After article review and quality assessment, 50 studies,
      including 18662 patients and 1313 healthy subjects, were analyzed. Presence of
      HCV genotype 3 versus genotype 1 was significantly associated with a higher
      frequency of CC genotype and C allele, with an odds ratio (OR) of 1.68 (95% CI:
      1.44-1.99) and 1.49 (95% CI: 1.33-1.67), respectively. Prevalence of the
      rs12979860 CC genotype among genotype 1 HCV infected patients of Asian ethnicity
      was 69.48% (95% CI: 65.20-73.77), which was significantly higher than its
      prevalence [33.27% (95% CI: 28.88-37.67)] in the Caucasian genotype 1 HCV
      infected patients. Prevalence of rs12979860 TT genotype in the African-American
      genotype 1 HCV infected patients was the highest [36.20% (95% CI: 32.91-39.49)],
      and significantly different compared to all other ethnicities. CONCLUSIONS: There
      were significant linkages between HCV genotypes and IL28B genotypes/alleles.
      Patients with a favorable IL28B and genotypes 1 and 4 HCV infection stand a
      better chance to clear HCV in the acute phase.

PMID- 24734093
TI  - Disappearance of Oral Lichen Planus After Liver Transplantation for Primary
      Biliary Cirrhosis and Immunosuppressive Therapy in a 63-year-Old Japanese Woman.
AB  - INTRODUCTION: There are few reports concerning association between primary
      biliary cirrhosis (PBC) and lichen planus. In addition, there is only one report
      about lichen planus after liver transplantation. CASE PRESENTATION: We describe a
      case of oral lichen planus (OLP) accompanied with PBC that resolved following
      liver transplantation 14 years later. This patient received immunosuppressive
      drugs after liver transplantation. DISCUSSION: The disappearance of OLP might be
      due to immunosuppressive therapy following liver transplantation. Further
      observations and studies are necessary to clarify the relationship between OLP
      and PBC.

PMID- 24734094
TI  - Skin Adverse Events During Dual and Triple Therapy for HCV-Related Cirrhosis.
AB  - INTRODUCTION: Dermatological adverse events are an existing concern during
      treatment of hepatitis C virus infection. Peginterferon/ribavirin treatment is
      associated with well-characterized dermatological lesions tending towards a
      uniform entity of dermatitis. New telaprevir- or boceprevir-based triple-therapy
      has led to significant improvements in sustained virological response rates,
      although associated with an increase in cutaneous adverse events compared
      peginterferon/ribavirin alone. CASE PRESENTATION: We report a case of a patient
      who discontinued telaprevir because of severe skin eruptions and who, during
      ribavirin and interferon treatment, after a period free of skin lesions,
      developed new dermatological lesions different than those experienced during
      telaprevir treatment. CONCLUSIONS: Several adverse effects are associated to anti
      HCV drugs, hence appropriate skin care management and follow-up are very
      important. A careful anamnesis before the initiation of triple therapy is
      necessary to identify previous dermatological diseases that could increase skin
      adverse effects incidence.

PMID- 24734095
TI  - Hepatitis B vaccination: needs a revision.

PMID- 24734096
TI  - Pneumothorax.
AB  - Pneumothorax-either spontaneous or iatrogenic-is commonly encountered in
      pulmonary medicine. While secondary pneumothorax is caused by an underlying
      pulmonary disease, the spontaneous type occurs in healthy individuals without
      obvious cause. The British Thoracic Society (BTS, 2010) and the American College
      of Chest Physicians (ACCP, 2001) published the guidelines for pneumothorax
      management. This review compares the diagnostic and management recommendations
      between the two societies. Patients diagnosed with primary spontaneous
      pneumothorax (PSP) may be observed without intervention if the pneumothorax is
      small and there are no symptoms. Oxygen therapy is only discussed in the BTS
      guidelines. If intervention is needed, BTS recommends a simple aspiration in all
      spontaneous and some secondary pneumothorax cases, whereas ACCP suggests a chest
      tube insertion rather than a simple aspiration. BTS and ACCP both recommend
      surgery for patients with a recurrent pneumothorax and persistent air leak. For
      patients who decline surgery or are poor surgical candidates, pleurodesis is an
      alternative recommended by both BTS and ACCP guidelines. Treatment strategies of
      iatrogenic pneumothorax are very similar to PSP. However, recurrence is not a
      consideration in iatrogenic pneumothorax. 

PMID- 24734097
TI  - Respiratory reviews in asthma 2013.
AB  - From January 2012 up until March 2013, many articles with huge clinical
      importance in asthma were published based on large numbered clinical trials or
      meta-analysis. The main subjects of these studies were the new therapeutic plan
      based on the asthma phenotype or efficacy along with the safety issues regarding
      the current treatment guidelines. For efficacy and safety issues, inhaled
      corticosteroid tapering strategy or continued long-acting beta agonists use was
      the major concern. As new therapeutic trials, monoclonal antibodies or macrolide
      antibiotics based on inflammatory phenotypes have been under investigation, with
      promising preliminary results. There were other issues on the disease
      susceptibility or genetic background of asthma, particularly for the "severe
      asthma" phenotype. In the era of genome and pharmacogenetics, there have been
      extensive studies to identify susceptible candidate genes based on the results of
      genome wide association studies (GWAS). However, for severe asthma, which is
      where most of the mortality or medical costs develop, it is very unclear.
      Moreover, there have been some efforts to find important genetic information in
      order to predict the possible disease progression, but with few significant
      results up until now. In conclusion, there are new on-going aspects in the
      phenotypic classification of asthma and therapeutic strategy according to the
      phenotypic variations. With more pharmacogenomic information and clear
      identification of the "severe asthma" group even before disease progression from
      GWAS data, more adequate and individualized therapeutic strategy could be
      realized in the future. 

PMID- 24734098
TI  - Schedule-Dependent Effect of Epigallocatechin-3-Gallate (EGCG) with Paclitaxel on
      H460 Cells.
AB  - BACKGROUND: Epigallocatechin-3-gallate (EGCG), a major biologically active
      component of green tea, has anti-cancer activity in human and animal models. We
      investigated the schedule-dependent effect of EGCG and paclitaxel on growth of
      NCI-H460 non-small cell lung cancer cells. METHODS: To investigate the combined
      effect of EGCG (E) and paclitaxel (P), combination indices (CIs) were calculated,
      and cell cycle analysis was performed. For the effect on cell apoptosis, western
      blot analysis was also performed. RESULTS: CI analysis demonstrated that both
      concurrent and sequential E -> P treatments had antagonistic effects (CIs >1.0),
      but sequential P -> E had synergistic effects (CIs <1.0), on the growth
      inhibition of NCI-H460 cells. In the cell cycle analysis, although paclitaxel
      induced G2/M cell cycle arrest and increased the sub-G1 fraction, concurrent EGCG
      and paclitaxel treatments did not have any additive or synergistic effects
      compared with the paclitaxel treatment alone. However, western blot analysis
      demonstrated that sequential P -> E treatment decreased the expression of Bcl-2
      and procaspase-3 and increased poly(ADP-ribose) polymerase (PARP) cleavage; while
      minimal effects were seen with concurrent or sequential E -> P treatments.
      CONCLUSION: Concurrent or sequential E -> P treatment had opposite effects to P 
      > E treatment, where P -> E treatment showed a synergistic effect on growth
      inhibition of NCI-H460 cells by inducing apoptosis. Thus, the efficacy of EGCG
      and paclitaxel combination treatment seems to be schedule-dependent.

PMID- 24734099
TI  - Apigenin and Wogonin Regulate Epidermal Growth Factor Receptor Signaling Pathway
      Involved in MUC5AC Mucin Gene Expression and Production from Cultured Airway
      Epithelial Cells.
AB  - BACKGROUND: We investigated whether wogonin and apigenin significantly affect the
      epidermal growth factor receptor (EGFR) signaling pathway involved in MUC5AC
      mucin gene expression, and production from cultured airway epithelial cells; this
      was based on our previous report that apigenin and wogonin suppressed MUC5AC
      mucin gene expression and production from human airway epithelial cells. METHODS:
      Confluent NCI-H292 cells were pretreated with wogonin or apigenin for 15 minutes
      or 24 hours and then stimulated with epidermal growth factor (EGF) for 24 hours
      or the indicated periods. RESULTS: We found that incubation of NCI-H292 cells
      with wogonin or apigenin inhibited the phosphorylation of EGFR. The downstream
      signals of EGFR such as phosphorylation of MEK1/2 and ERK1/2 were also inhibited
      by wogonin or apigenin. CONCLUSION: The results suggest that wogonin and apigenin
      inhibits EGFR signaling pathway, which may explain how they inhibit MUC5AC mucin
      gene expression and production induced by EGF.

PMID- 24734100
TI  - Effect of rivaroxaban on fibrinolytic therapy in massive pulmonary embolism: two
      cases.
AB  - The risk of dying from a pulmonary embolism (PE) is estimated to be about 30% if
      inotropic support is required and no cardiopulmonary arrest occurs. Fibrinolysis
      in massive PE is regarded as a life-saving intervention, unless there is a high
      risk of bleeding following the use of the fibrinolytic therapy. Rivaroxaban is an
      oral factor Xa inhibitor, however its anticoagulation effects before or after
      administration of fibrinolytics in massive PE are still unknown. Two patents were
      admitted: 61-year-old woman with repeated syncope, and a 73-year-old woman was
      admitted with dyspnea and poor oral intake. Systemic arterial hypotension with
      radiologic confirmation led to a diagnosis of massive PE in both patients.
      Rivaroxaban was administered before in one, and after firbrinolytic therapy in
      the other. One showed similar efficacy of rivaroxaban with currently used
      anticoagulants after successful fibrinolysis, and the other one without
      antecedent administration of the fibrinolytic agent showed unfavorable efficacy
      of rivaroxaban. 

PMID- 24734101
TI  - Endometrial stromal sarcoma presented as an incidental lung mass with multiple
      pulmonary nodules.
AB  - Low-grade endometrial stromal sarcoma (ESS) is an uncommon gynecologic malignancy
      of mesodermal origin. Pulmonary metastasis of low-grade ESS can occur years and
      decades after the treatment of the primary disease. Low-grade ESS is frequently
      mistaken as benign uterine neoplasm like uterine leiomyoma, which can potentially
      lead to a misdiagnosis. We present a case of a 42-year-old woman with low-grade
      ESS, that initially presented as an incidental lung mass with multiple pulmonary
      nodules, seven years after an uterine myomectomy. A 6.9*5.8 cm-sized intrapelvic
      mass suspected of uterine origin was discovered while searching for potential
      extrathoracic primary origin. A pelviscopy and simultaneous thoracoscopic lung
      biopsy were conducted for pathologic diagnosis. Finally, the diagnosis was
      confirmed as low-grade ESS with lung metastasis based on the histopathologic
      examination with immunohistochemical stain, which was showed positive for CD10
      and hormone receptor markers (estrogen and progesterone receptors) in both pelvic
      and lung specimens. 

PMID- 24734102
TI  - A case of pulmonary artery sarcoma presented as cavitary pulmonary lesions.
AB  - Pulmonary artery sarcoma (PAS) is a rare, poorly differentiated malignancy
      arising from the intimal layer of the pulmonary artery. Contrast-enhanced chest
      computed tomography (CT) is a good diagnostic modality that shows a low
      attenuation filling defect of the pulmonary artery in PAS patients. An 18-year
      old man was referred to our hospital for the evaluation and management of
      cavitary pulmonary lesions that did not respond to treatment. A contrast-enhanced
      CT of the chest was performed, which showed a filling defect within the right
      interlobar pulmonary artery. The patient underwent a curative right pneumonectomy
      after confirmation of PAS. Although lung parenchymal lesions of PAS are generally
      nonspecific, it can be presented as cavities indicate pulmonary infarcts.
      Clinicians must consider the possibility of PAS as well as pulmonary
      thromboembolism in patients with pulmonary infarcts. So, we report the case with
      PAS that was diagnosed during the evaluation of cavitary pulmonary lesions and
      reviewed the literatures. 

PMID- 24734103
TI  - Two Cases of Diagnosis and Removal of Endobronchial Hamartoma by Cryotherapy via
      Flexible Bronchoscopy.
AB  - Although endobronchial hamartoma is a rare benign tumor, most patients with
      endobronchial hamartoma have respiratory symptoms such as obstructive pneumonia,
      hemoptysis, cough, or dyspnea due to bronchial obstruction. It can cause
      irreversible post-obstructive pulmonary destruction, thus early diagnosis and
      treatment is very important. Recently, there have been cases of neodymium-doped
      yttrium aluminum garnet (Nd:YAG) laser and electrocautery procedures for
      bronchoscopic treatment of malignant or benign central airway obstruction with
      comparable therapeutic efficacy and few complications. Bronchoscopic cryotherapy
      is a newly developed technique for management of central airway obstruction.
      Moreover, it provides diagnostic methods with improving diagnostic yield and
      safety. We report two cases of endobronchial hamartoma, each diagnosed and
      definitively treated with bronchoscopic techniques. Endobronchial biopsy and
      removal was successfully performed by cryotherapy via flexible bronchoscopy
      without notable complications. Follow-up bronchoscopic examinations excluded
      residual or recurrent disease. 

PMID- 24734104
TI  - Hedyotis diffusa Combined with Scutellaria barbata Are the Core Treatment of
      Chinese Herbal Medicine Used for Breast Cancer Patients: A Population-Based
      Study.
AB  - Traditional Chinese medicine (TCM), which is the most common type of
      complementary and alternative medicine (CAM) used in Taiwan, is increasingly used
      to treat patients with breast cancer. However, large-scale studies on the
      patterns of TCM prescriptions for breast cancer are still lacking. The aim of
      this study was to determine the core treatment of TCM prescriptions used for
      breast cancer recorded in the Taiwan National Health Insurance Research Database.
      TCM visits made for breast cancer in 2008 were identified using ICD-9 codes. The
      prescriptions obtained at these TCM visits were evaluated using association rule
      mining to evaluate the combinations of Chinese herbal medicine (CHM) used to
      treat breast cancer patients. A total of 37,176 prescriptions were made for 4,436
      outpatients with breast cancer. Association rule mining and network analysis
      identified Hedyotis diffusa plus Scutellaria barbata as the most common duplex
      medicinal (10.9%) used for the core treatment of breast cancer. Jia-Wei-Xiao-Yao
      San (19.6%) and Hedyotis diffusa (41.9%) were the most commonly prescribed herbal
      formula (HF) and single herb (SH), respectively. Only 35% of the commonly used
      CHM had been studied for efficacy. More clinical trials are needed to evaluate
      the efficacy and safety of these CHM used to treat breast cancer. 

PMID- 24734106
TI  - Inhibitory Effects of Gymnema (Gymnema sylvestre) Leaves on Tumour Promotion in
      Two-Stage Mouse Skin Carcinogenesis.
AB  - Ethanol extracts of gymnema (Gymnema sylvestre) leaves exhibited marked
      antitumour-promoting activity in an in vivo two-stage carcinogenesis test in mice
      using 7,12-dimethylbenz[a]anthracene as an initiator and 12-O
      tetradecanoylphorbol-13-acetate (TPA) as a promoter. From the active fraction of
      the ethanol extract of the gymnema leaves, three triterpenoids were isolated and
      identified. These compounds were evaluated for their inhibitory effects on TPA
      induced inflammation (1 ug/ear) in mice. The tested compounds showed marked anti
      inflammatory effects, with a 50% inhibitory dose of 50-555 nmol/ear. 

PMID- 24734105
TI  - Toad glandular secretions and skin extractions as anti-inflammatory and
      anticancer agents.
AB  - Toad glandular secretions and skin extractions contain many natural agents which
      may provide a unique resource for novel drug development. The dried secretion
      from the auricular and skin glands of Chinese toad (Bufo bufo gargarizans) is
      named Chansu, which has been used in Traditional Chinese Medicine (TCM) for
      treating infection and inflammation for hundreds of years. The sterilized hot
      water extraction of dried toad skin is named Huachansu (Cinobufacini) which was
      developed for treating hepatitis B virus (HBV) and several types of cancers.
      However, the mechanisms of action of Chansu, Huachansu, and their constituents
      within are not well reported. Existing studies have suggested that their anti
      inflammation and anticancer potential were via targeting Nuclear Factor (NF)
      kappaB and its signalling pathways which are crucial hallmarks of inflammation
      and cancer in various experimental models. Here, we review some current studies
      of Chansu, Huachansu, and their compounds in terms of their use as both anti
      inflammatory and anticancer agents. We also explored the potential use of toad
      glandular secretions and skin extractions as alternate resources for treating
      human cancers in combinational therapies. 

PMID- 24734107
TI  - Clinical Study of Effects of Jian Ji Ning, a Chinese Herbal Medicine Compound
      Preparation, in Treating Patients with Myasthenia Gravis via the Regulation of
      Differential MicroRNAs Expression in Serum.
AB  - Myasthenia gravis (MG) is an autoimmune disease, of which the pathogenesis has
      remained unclear. At present, MG does not have any effective treatment with minor
      side effects. Jian Ji Ning (JJN), a traditional Chinese medicine formula
      consisting of 11 medicinal plants, has been used in the treatment of MG for many
      years. The present study aims to determine if the Chinese herbal medicine JJN
      could lighten the clinical symptoms of patients with MG via the regulation of
      differential microRNAs (miRNAs) expression in serum. JJN should be orally
      administered twice a day for 6 months. In the efficacy evaluation adopting the
      Quantitative Myasthenia Gravis Score (QMG), we found that JJN could improve the
      clinical symptoms of patients with MG more effectively. Besides, we found that
      JJN could regulate differential miRNAs expression in serum of patients with MG.
      Accordingly, we speculate that the effects of JJN on improving clinical symptoms
      and blood test indicators of patients with MG may be due to its inhibition of
      apoptotic pathways of some immune cells and its connection with the regulation of
      serum miRNAs of some patients. In conclusion, we believe that JJN has a reliable
      curative effect on patients with MG-induced neuropathologic changes. 

PMID- 24734108
TI  - Acupuncture Enhances Effective Connectivity between Cerebellum and Primary
      Sensorimotor Cortex in Patients with Stable Recovery Stroke.
AB  - Recent neuroimaging studies have demonstrated that stimulation of acupuncture at
      motor-implicated acupoints modulates activities of brain areas relevant to the
      processing of motor functions. This study aims to investigate acupuncture-induced
      changes in effective connectivity among motor areas in hemiparetic stroke
      patients by using the multivariate Granger causal analysis. A total of 9 stable
      recovery stroke patients and 8 healthy controls were recruited and underwent
      three runs of fMRI scan: passive finger movements and resting state before and
      after manual acupuncture stimuli. Stroke patients showed significantly attenuated
      effective connectivity between cortical and subcortical areas during passive
      motor task, which indicates inefficient information transmissions between
      cortical and subcortical motor-related regions. Acupuncture at motor-implicated
      acupoints showed specific modulations of motor-related network in stroke patients
      relative to healthy control subjects. This specific modulation enhanced
      bidirectionally effective connectivity between the cerebellum and primary
      sensorimotor cortex in stroke patients, which may compensate for the attenuated
      effective connectivity between cortical and subcortical areas during passive
      motor task and, consequently, contribute to improvement of movement coordination
      and motor learning in subacute stroke patients. Our results suggested that
      further efficacy studies of acupuncture in motor recovery can focus on the
      improvement of movement coordination and motor learning during motor
      rehabilitation. 

PMID- 24734109
TI  - Neuronal Activity Stimulated by Liquid Substrates Injection at Zusanli (ST36)
      Acupoint: The Possible Mechanism of Aquapuncture.
AB  - Aquapuncture is a modified acupuncture technique and it is generally accepted
      that it has a greater therapeutic effect than acupuncture because of the
      combination of the acupoint stimulation and the pharmacological effect of the
      drugs. However, to date, the mechanisms underlying the effects of aquapuncture
      remain unclear. We hypothesized that both the change in the local spatial
      configuration and the substrate stimulation of aquapuncture would activate
      neuronal signaling. Thus, bee venom, normal saline, and vitamins B1 and B12 were
      injected into a Zusanli (ST36) acupoint as substrate of aquapuncture, whereas a
      dry needle was inserted into ST36 as a control. After aquapuncture, activated
      neurons expressing Fos protein were mainly observed in the dorsal horn of the
      spinal cord in lumbar segments L3-5, with the distribution nearly identical among
      all groups. However, the bee venom injection induced significantly more Fos
      expressing neurons than the other substrates. Based on these data, we suggest
      that changes in the spatial configuration of the acupoint activate neuronal
      signaling and that bee venom may further strengthen this neuronal activity. In
      conclusion, the mechanisms for the effects of aquapuncture appear to be the
      spatial configuration changes occurring within the acupoint and the ability of
      injected substrates to stimulate neuronal activity. 

PMID- 24734110
TI  - Characterization and Quantification of Compounds in the Hydroalcoholic Extract of
      the Leaves from Terminalia catappa Linn. (Combretaceae) and Their Mutagenic
      Activity.
AB  - Terminalia is a genus of Combretaceous plants widely distributed in tropical and
      subtropical regions. Thus, the aim of this study was to quantify the majority
      compounds of the hydroalcoholic extract (7 : 3, v/v) of the leaves from T.
      catappa by HPLC-PDA, chemically characterize by hyphenated techniques (HPLC-ESI
      IT-MS(n)) and NMR, and evaluate its mutagenic activity by the
      Salmonella/microsome assay on S. typhimurium strains TA98, TA97a, TA100, and
      TA102. The quantification of analytes was performed using an external calibration
      standard. Punicalagin is the most abundant polyphenol found in the leaves. The
      presence of this compound as a mixture of anomers was confirmed using HPLC-PDA
      and (1)H and (13)C NMR. Mutagenic activity was observed in strains TA100 and
      TA97a. As the extract is a complex mixture of punicalagin, its derivatives, and
      several other compounds, the observed mutagenicity may be explained in part by
      possible synergistic interaction between the compounds present in the extract.
      These studies show that mutagenic activity of T. catappa in the Ames test can
      only be observed when measured at high concentrations. However, considering the
      mutagenic effects observed for T. catappa, this plant should be used cautiously
      for medicinal purposes. 

PMID- 24734111
TI  - How to assess the external validity and model validity of therapeutic trials: a
      conceptual approach to systematic review methodology.
AB  - Background. Evidence rankings do not consider equally internal (IV), external
      (EV), and model validity (MV) for clinical studies including complementary and
      alternative medicine/integrative medicine (CAM/IM) research. This paper describe
      this model and offers an EV assessment tool (EVAT(c)) for weighing studies
      according to EV and MV in addition to IV. Methods. An abbreviated systematic
      review methodology was employed to search, assemble, and evaluate the literature
      that has been published on EV/MV criteria. Standard databases were searched for
      keywords relating to EV, MV, and bias-scoring from inception to Jan 2013. Tools
      identified and concepts described were pooled to assemble a robust tool for
      evaluating these quality criteria. Results. This study assembled a streamlined,
      objective tool to incorporate for the evaluation of quality of EV/MV research
      that is more sensitive to CAM/IM research. Conclusion. Improved reporting on EV
      can help produce and provide information that will help guide policy makers,
      public health researchers, and other scientists in their selection, development,
      and improvement in their research-tested intervention. Overall, clinical studies
      with high EV have the potential to provide the most useful information about
      "real-world" consequences of health interventions. It is hoped that this novel
      tool which considers IV, EV, and MV on equal footing will better guide clinical
      decision making. 

PMID- 24734112
TI  - Scientific basis of mind-body interventions.

PMID- 24734113
TI  - Acupuncture modulates the functional connectivity of the default mode network in
      stroke patients.
AB  - Abundant evidence from previous fMRI studies on acupuncture has revealed
      significant modulatory effects at widespread brain regions. However, few reports
      on the modulation to the default mode network (DMN) of stroke patients have been
      investigated in the field of acupuncture. To study the modulatory effects of
      acupuncture on the DMN of stroke patients, eight right hemispheric infarction and
      stable ischemic stroke patients and ten healthy subjects were recruited to
      undergo resting state fMRI scanning before and after acupuncture stimulation.
      Functional connectivity analysis was applied with the bilateral posterior
      cingulate cortices chosen as the seed regions. The main finding demonstrated that
      the interregional interactions between the ACC and PCC especially enhanced after
      acupuncture at GB34 in stroke patients, compared with healthy controls. The
      results indicated that the possible mechanisms of the modulatory effects of
      acupuncture on the DMN of stroke patients could be interpreted in terms of
      cognitive ability and motor function recovery. 

PMID- 24734114
TI  - Medicinal plants and ethnomedicine in peril: a case study from Nepal himalaya.
AB  - The impacts of climate change were severe on indigenous medicinal plant species
      and their dependent communities. The harvesting calendar and picking sites of
      these species were no longer coinciding and the changes were affecting
      harvesters' and cultivators' abilities to collect and use those species.
      Secondary sites: road-heads, wastelands, regenerated forests, and so forth, were
      being prioritized for collection and the nonindigenous medicinal plant species
      were being increasingly introduced into the medical repertoire as a substitution
      and to diversify the local medicinal stock. Acceptance and application of
      nonindigenous species and sites for livelihood and ethnopharmacopoeias with
      caution were considered as an important adaptation strategy. Findings on species
      and site specific accounts urged further researches on medicinal plants,
      ethnomedicine, and their interrelationship with impacts of climate change. 

PMID- 24734115
TI  - Statistical genetics and its applications in medical studies.

PMID- 24734116
TI  - A hybrid approach of using symmetry technique for brain tumor segmentation.
AB  - Tumor and related abnormalities are a major cause of disability and death
      worldwide. Magnetic resonance imaging (MRI) is a superior modality due to its
      noninvasiveness and high quality images of both the soft tissues and bones. In
      this paper we present two hybrid segmentation techniques and their results are
      compared with well-recognized techniques in this area. The first technique is
      based on symmetry and we call it a hybrid algorithm using symmetry and active
      contour (HASA). In HASA, we take refection image, calculate the difference image,
      and then apply the active contour on the difference image to segment the tumor.
      To avoid unimportant segmented regions, we improve the results by proposing an
      enhancement in the form of the second technique, EHASA. In EHASA, we also take
      reflection of the original image, calculate the difference image, and then change
      this image into a binary image. This binary image is mapped onto the original
      image followed by the application of active contouring to segment the tumor
      region. 

PMID- 24734117
TI  - A new multistage medical segmentation method based on superpixel and fuzzy
      clustering.
AB  - The medical image segmentation is the key approach of image processing for brain
      MRI images. However, due to the visual complex appearance of image structures and
      the imaging characteristic, it is still challenging to automatically segment
      brain MRI image. A new multi-stage segmentation method based on superpixel and
      fuzzy clustering (MSFCM) is proposed to achieve the good brain MRI segmentation
      results. The MSFCM utilizes the superpixels as the clustering objects instead of
      pixels, and it can increase the clustering granularity and overcome the influence
      of noise and bias effectively. In the first stage, the MRI image is parsed into
      several atomic areas, namely, superpixels, and a further parsing step is adopted
      for the areas with bigger gray variance over setting threshold. Subsequently,
      designed fuzzy clustering is carried out to the fuzzy membership of each
      superpixel, and an iterative broadcast method based on the Butterworth function
      is used to redefine their classifications. Finally, the segmented image is
      achieved by merging the superpixels which have the same classification label. The
      simulated brain database from BrainWeb site is used in the experiments, and the
      experimental results demonstrate that MSFCM method outperforms the traditional
      FCM algorithm in terms of segmentation accuracy and stability for MRI image. 

PMID- 24734118
TI  - Deep learning based syndrome diagnosis of chronic gastritis.
AB  - In Traditional Chinese Medicine (TCM), most of the algorithms used to solve
      problems of syndrome diagnosis are superficial structure algorithms and not
      considering the cognitive perspective from the brain. However, in clinical
      practice, there is complex and nonlinear relationship between symptoms (signs)
      and syndrome. So we employed deep leaning and multilabel learning to construct
      the syndrome diagnostic model for chronic gastritis (CG) in TCM. The results
      showed that deep learning could improve the accuracy of syndrome recognition.
      Moreover, the studies will provide a reference for constructing syndrome
      diagnostic models and guide clinical practice. 

PMID- 24734119
TI  - Enhancing the detection of BOLD signal in fMRI by reducing the partial volume
      effect.
AB  - PURPOSE: To investigate the advantages of reducing the partial volume effect
      (PVE) to enhance the detection of the BOLD signal in fMRI. METHODS: A linear
      phase term was added in k-space to obtain half-voxel shifting of 64 * 64 T2*
      weighted echo-planar images. Three sets of image data shifted in the x, y, and
      diagonal direction, respectively, are combined with the original 64 * 64 data to
      form the 128 * 128 voxel-shifted interpolated data. RESULTS: A simulation of a
      synthetic fMRI dataset shows that the voxel-shifted interpolation (VSI) can
      increase the t-score up to 50% in single-voxel activations. An fMRI study (n = 7)
      demonstrates that 20.4% of the interpolated voxels have higher t-scores than
      their nearest neighboring voxels in the original maps. The average increase of
      the t-score in these interpolated voxels is 13.3%. CONCLUSION: VSI yields
      increased sensitivity in detecting voxel-size BOLD activations, improved spatial
      accuracy of activated regions, and improved detection of the peak BOLD signal of
      an activated region. VSI can potentially be used as an alternative to the high
      resolution fMRI studies in which reduction in SNR and increase in imaging time
      become prohibitive.

PMID- 24734120
TI  - An inulin and doxorubicin conjugate for improving cancer therapy.
AB  - Chemotherapy is one of the primary treatment mechanisms for treating cancer.
      Current chemotherapy is systemically delivered and causes significant side
      effects; therefore the development of new chemotherapeutic agents or enhancing
      the effectiveness of current chemotherapeutic could prove vital to patients and
      cancer care. The purpose of this research was to develop a new conjugate composed
      of doxorubicin (chemotherapeutic) and inulin (polysaccharide chain) and evaluate
      its potential as a new therapeutic agent for cancer treatment. The synergistic
      effect of inulin conjugated to doxorubicin has allowed the same cytotoxic
      response to be maintained or improved at lower doses as compared to doxorubicin.
      Supporting results include cytotoxicity profiles, calf thymus DNA binding
      studies, confocal microscopy, and transport studies.

PMID- 24734122
TI  - Analysis of electronic medication orders with large overdoses: opportunities for
      mitigating dosing errors.
AB  - BACKGROUND: Users of electronic health record (EHR) systems frequently prescribe
      doses outside recommended dose ranges, and tend to ignore the alerts that result.
      Since some of these dosing errors are the result of system design flaws, analysis
      of large overdoses can lead to the discovery of needed system changes.
      OBJECTIVES: To develop database techniques for detecting and extracting large
      overdose orders from our EHR. To identify and characterize users' responses to
      these large overdoses. To identify possible causes of large-overdose errors and
      to mitigate them. METHODS: We constructed a data mart of medication-order and
      dosing-alert data from a quaternary pediatric hospital from June 2011 to May
      2013. The data mart was used along with a test version of the EHR to explain how
      orders were processed and alerts were generated for large (>500%) and extreme
      (>10,000%) overdoses. User response was characterized by the dosing alert
      salience rate, which expresses the proportion of time users take corrective
      action. RESULTS: We constructed an advanced analytic framework based on workflow
      analysis and order simulation, and evaluated all 5,402,504 medication orders
      placed within the 2 year timeframe as well as 2,232,492 dose alerts associated
      with some of the orders. 8% of orders generated a visible alert, with 1/4 of
      these related to overdosing. Alerts presented to trainees had higher salience
      rates than those presented to senior colleagues. Salience rates were low, varying
      between 4-10%, and were lower with larger overdoses. Extreme overdoses fell into
      eight causal categories, each with a system design mitigation. CONCLUSIONS: Novel
      analytic systems are required to accurately understand prescriber behavior and
      interactions with medication-dosing CDS. We described a novel analytic system
      that can detect apparent large overdoses (>=500%) and explain the sociotechnical
      factors that drove the error. Some of these large overdoses can be mitigated by
      system changes. EHR design should prospectively mitigate these errors.

PMID- 24734121
TI  - An exploratory, population-based, mixed-methods program evaluation of user
      satisfaction of services provided by a regional extension center (REC).
AB  - OBJECTIVES: To evaluate user satisfaction among practices receiving services
      provided by the Arizona Regional Extension Center (REC). METHODS: This program
      evaluation utilized a mixed-methods approach including: 1) a mail-based survey
      targeting all 489 REC member practices; and 2) a series of telephone-based focus
      groups using a convenience sample of rural and urban REC member practices.
      Targeted respondents were key contacts who handle interactions with the REC at
      each practice. Program evaluators at the University of Arizona and experts at
      Arizona Health-e Connection (AzHeC) created the questionnaires, focus group
      script, participant invitation and follow up documents via a collaborative
      process. Regression and Rasch analyses were used to identify key factors
      associated with satisfaction with REC and to assess questionnaire validity,
      respectively. RESULTS: Responses from both the focus groups and survey revealed
      that most of the respondents were satisfied with the current services, despite
      the presence of satisfaction gaps between practices of various characteristics:
      respondents that were clinicians, practices using web-based electronic health
      record systems (EHRs), and practices that had achieved Stage 1 Meaningful Use had
      a higher level of satisfaction compared with their respective counterparts. Focus
      group participants provided suggestions for improving REC services. CONCLUSIONS:
      Most respondents reported being satisfied with REC services. Specialized
      representatives may be needed for practices at different stages of Meaningful Use
      to further improve REC satisfaction in order to facilitate more efficient
      adoption of EHRs.

PMID- 24734123
TI  - Burden on university hospitals of handling portable data for imaging (PDI) media.
AB  - BACKGROUND: Portable Data for Imaging (PDI) is regularly used as a guideline for
      sharing medical imaging data between hospitals and other medical institutions.
      When a patient is referred to another location, the patient almost always brings
      PDI media on a CD or DVD. However, problems often occur when trying to view
      images on PDI discs inserted into computer terminals, and it is more efficient to
      view images on the hospitals' own picture archiving and communication system
      (PACS). On the request of doctors, it has become a routine practice to import PDI
      data to the PACS of the referred hospital. OBJECTIVE: The aim of this study was
      to analyze the increase in PDI image importing and investigate methods for
      reducing the burden caused by importing images. METHODS: We compiled
      representative data on image importing over time and analyzed the test
      modalities, number of images, volume of data, and referring hospital or medical
      clinic from which the data originated. RESULTS: The amount of PDI images imported
      to the PACS has risen despite no large increase in the number of patients.
      Currently, images imported from PDI media make up 22.8% of the total number of
      images stored in the PACS. The images come from a diverse array of hospitals (184
      hospitals) and 82% are essential for medical care. The total annual expenditure
      associated with PDI data management is estimated to be 98,300 USD. CONCLUSION:
      The spreading use of the PDI guideline has led to a dramatic increase in data
      image sharing in the field of healthcare. While this has great benefits for
      patients and doctors, it is also associated with a greater cost and an overall
      burden for hospitals. These results indicate the need for a system to enable many
      hospitals and clinics to participate in image sharing at a cheaper cost.

PMID- 24734125
TI  - Generating sensor data summaries to communicate change in elders' health status.
AB  - BACKGROUND: Sensor systems detect critical health changes of frail residents in
      the community. However, sensor systems alone may not allow users to identify data
      trends fast enough. Linguistic summaries of sensor data describing elder activity
      in their apartment provide a useful solution so clinicians can respond quicker.
      OBJECTIVES: This paper describes two case studies of independent elders living
      with sensors in their assisted living apartment. Residents experienced declining
      health status and activity level over a period of approximately 24 months.
      Linguistic summaries were assessed iteratively by engineers and nurses working
      with the sensor system. METHODS: We created summaries of activity data collected
      from sensors located in resident apartments during a period of health status
      change. Engineers distilled information from heterogeneous data sources including
      bedroom motion and bed restlessness sensors during the summarization process.
      Engineers used fuzzy measures to compare two different periods of nighttime
      activity. Using iterative approaches a registered nurse worked with the team to
      develop algorithms and short phrases that appropriately capture and describe
      changes in activity levels. RESULTS: Total activity levels captured by sensors
      were graphed for two elderly residents experiencing health problems over a period
      of months. In the first case study (resident 3004), an elderly resident had knee
      surgery and onset of backspasms postoperatively. Graphed dissimilar measures show
      changes from baseline when backspasms occur. In the second case study (resident
      3003), there were increased periods of bed restlessness before and after a
      resident had a major surgical procedure. During these periods, graphs of
      dissimilarity measures indicate that there were changes from usual baseline
      periods of restlessness postoperatively indicating the health problems were
      persisting. Nurse care coordination notes indicate these episodes were related to
      poor pain control. CONCLUSIONS: Summaries of activity change are useful for care
      coordinators to detect resident health status for community dwelling residents.

PMID- 24734124
TI  - Towards prevention of acute syndromes: electronic identification of at-risk
      patients during hospital admission.
AB  - BACKGROUND: Identifying patients at risk for acute respiratory distress syndrome
      (ARDS) before their admission to intensive care is crucial to prevention and
      treatment. The objective of this study is to determine the performance of an
      automated algorithm for identifying selected ARDS predisposing conditions at the
      time of hospital admission. METHODS: This secondary analysis of a prospective
      cohort study included 3,005 patients admitted to hospital between January 1 and
      December 31, 2010. The automated algorithm for five ARDS predisposing conditions
      (sepsis, pneumonia, aspiration, acute pancreatitis, and shock) was developed
      through a series of queries applied to institutional electronic medical record
      databases. The automated algorithm was derived and refined in a derivation cohort
      of 1,562 patients and subsequently validated in an independent cohort of 1,443
      patients. The sensitivity, specificity, and positive and negative predictive
      values of an automated algorithm to identify ARDS risk factors were compared with
      another two independent data extraction strategies, including manual data
      extraction and ICD-9 code search. The reference standard was defined as the
      agreement between the ICD-9 code, automated and manual data extraction. RESULTS:
      Compared to the reference standard, the automated algorithm had higher
      sensitivity than manual data extraction for identifying a case of sepsis (95% vs.
      56%), aspiration (63% vs. 42%), acute pancreatitis (100% vs. 70%), pneumonia (93%
      vs. 62%) and shock (77% vs. 41%) with similar specificity except for sepsis and
      pneumonia (90% vs. 98% for sepsis and 95% vs. 99% for pneumonia). The PPV for
      identifying these five acute conditions using the automated algorithm ranged from
      65% for pneumonia to 91 % for acute pancreatitis, whereas the NPV for the
      automated algorithm ranged from 99% to 100%. CONCLUSION: A rule-based electronic
      data extraction can reliably and accurately identify patients at risk of ARDS at
      the time of hospital admission.

PMID- 24734126
TI  - Symposium highlights and synopses of the scientific program: the Sixth Annual Mid
      Atlantic Healthcare Informatics Symposium.
AB  - As the bar to actively participate in one's own health is consistently lowered
      through technology, patients are helping to evolve traditional workflows to make
      data more accessible at the point of care. This growing trend of patient
      engagement and personalized medicine was the focus of the 2013 Mid-Atlantic
      Healthcare Informatics Symposium in Philadelphia, PA on April 26, 2013. The
      conference, presented annually by the Center for Bio-medical Informatics (CBMi)
      at The Children's Hospital of Philadelphia, featured plenary sessions, panel
      discussions, and paper presentations on a range of topics, including patient
      engagement and personalized medicine; using data and analytics to optimize
      patient care; nursing informatics; and the future of biomedical informatics. 

PMID- 24734127
TI  - CAH to CAH: EHR implementation advice to critical access hospitals from peer
      experts and other key informants.
AB  - The US government allocated $30 billion to implement electronic health records
      (EHRs) in hospitals and provider practices through policy addressing Meaningful
      Use (MU). Most small, rural hospitals, particularly those designated as Critical
      Access Hospitals (CAHs), comprising nearly a quarter of US hospitals, had not
      implemented EHRs before. Little is known about implementation in this setting.
      Socio-technical factors differ between larger hospitals and CAHs, which continue
      to lag behind other hospitals in EHR adoption. OBJECTIVE: The main objective is
      to provide EHR implementation advice for CAHs from a spectrum of experts with an
      emphasis on recommendations from their peers at CAHs that have undertaken the
      process. The secondary objective is to begin to identify implementation process
      differences at CAHs v. larger hospitals. METHODS: We interviewed 41 experts,
      including 16 CAH staff members from EHR teams at 10 CAHs that recently
      implemented EHRs. We qualitatively analyzed the interviews to ascertain themes
      and implementation recommendations. RESULTS: Nineteen themes emerged. Under each
      theme, comments by experts provide in-depth advice on all implementation stages
      including ongoing optimization and use. We present comments for three top themes
      as ranked by number of CAH peer experts commenting - EHR System Selection, EHR
      Team, and Preparatory Work - and for two others, Outside Partners/Resources and
      Clinical Decision Support (CDS)/Knowledge Management (KM). Comments for remaining
      themes are included in tables. DISCUSSION: CAH experts rank the themes
      differently from all experts, a likely indication of the differences between
      hospitals. Comments for each theme indicate the specific difficulties CAHs
      encountered. CAH staffs have little or no EHR experience before implementation. A
      factor across themes is insufficient system and process knowledge, compounded by
      compressed implementation schedules. Increased, proactive self-education, via
      available outside partners and information resources, will mitigate difficulties
      and aid CAHs in meeting increased CDS requirements in MU Stages 2 and 3.

PMID- 24734128
TI  - A rigorous algorithm to detect and clean inaccurate adult height records within
      EHR systems.
AB  - BACKGROUND: Height is a critical variable for many biomedical analyses because it
      is an important component of Body Mass Index (BMI). Transforming EHR height
      measures into meaningful research-ready values is challenging and there is
      limited information available on methods for "cleaning" these data. OBJECTIVES:
      We sought to develop an algorithm to clean adult height data extracted from EHR
      using only height values and associated ages. RESULTS: The algorithm we developed
      is sensitive to normal decreases in adult height associated with aging, is
      implemented using an open-source software tool and is thus easily modifiable, and
      is freely available. We checked the performance of our algorithm using data from
      the Northwestern biobank and a replication sample from the Marshfield Clinic
      biobank obtained through our participation in the eMERGE consortium. The
      algorithm identified 1262 erroneous values from a total of 33937 records in the
      Northwestern sample. Replacing erroneous height values with those identified as
      correct by the algorithm resulted in meaningful changes in height and BMI
      records; median change in recorded height after cleaning was 7.6 cm and median
      change in BMI was 2.9 kg/m(2). Comparison of cleaned EHR height values to
      observer measured values showed that 94.5% (95% C.I 93.8-% - 95.2%) of cleaned
      values were within 3.5 cm of observer measured values. CONCLUSIONS: Our freely
      available height algorithm cleans EHR height data with only height and age
      inputs. Use of this algorithm will benefit groups trying to perform research with
      height and BMI data extracted from EHR.

PMID- 24734129
TI  - Methods and applications for visualization of SNOMED CT concept sets.
AB  - Inconsistent use of SNOMED CT concepts may reduce comparability of information in
      health information systems. Terminology implementation should be approached by
      common strategies for navigating and selecting proper concepts. This study aims
      to explore ways of illustrating common pathways and ancestors of particular sets
      of concepts, to support consistent use of SNOMED CT and also assess potential
      applications for such visualizations. The open source prototype presented is an
      interactive web-based re-implementation of the terminology visualization tool
      TermViz that provides an overview of concepts and their hierarchical relations.
      It provides terminological features such as interactively rearranging graphs,
      fetching more concept nodes, highlighting least common parents and shared
      pathways in merged graphs etc. Four teams of three to four people used the
      prototype to complete a terminology mapping task and then, in focus group
      interviews, discussed the user experience and potential future tool usage.
      Potential purposes discussed included SNOMED CT search and training, consistent
      selection of concepts and content management. The evaluation indicated that the
      tool may be useful in many contexts especially if integrated with existing
      systems, and that the graph layout needs further tuning and development. 

PMID- 24734130
TI  - A qualitative analysis evaluating the purposes and practices of clinical
      documentation.
AB  - OBJECTIVES: An important challenge for biomedical informatics researchers is
      determining the best approach for healthcare providers to use when generating
      clinical notes in settings where electronic health record (EHR) systems are used.
      The goal of this qualitative study was to explore healthcare providers' and
      administrators' perceptions about the purpose of clinical documentation and their
      own documentation practices. METHODS: We conducted seven focus groups with a
      total of 46 subjects composed of healthcare providers and administrators to
      collect knowledge, perceptions and beliefs about documentation from those who
      generate and review notes, respectively. Data were analyzed using inductive
      analysis to probe and classify impressions collected from focus group subjects.
      RESULTS: We observed that both healthcare providers and administrators believe
      that documentation serves five primary domains: clinical, administrative, legal,
      research, education. These purposes are tied closely to the nature of the
      clinical note as a document shared by multiple stakeholders, which can be a
      source of tension for all parties who must use the note. Most providers reported
      using a combination of methods to complete their notes in a timely fashion
      without compromising patient care. While all administrators reported relying on
      computer-based documentation tools to review notes, they expressed a desire for a
      more efficient method of extracting relevant data. CONCLUSIONS: Although clinical
      documentation has utility, and is valued highly by its users, the development and
      successful adoption of a clinical documentation tool largely depends on its
      ability to be smoothly integrated into the provider's busy workflow, while
      allowing the provider to generate a note that communicates effectively and
      efficiently with multiple stakeholders.

PMID- 24734131
TI  - Determining primary care physician information needs to inform ambulatory visit
      note display.
AB  - BACKGROUND: With the increase in the adoption of electronic health records (EHR)
      across the US, primary care physicians are experiencing information overload. The
      purpose of this pilot study was to determine the information needs of primary
      care physicians (PCPs) as they review clinic visit notes to inform EHR display.
      METHOD: Data collection was conducted with 15 primary care physicians during semi
      structured interviews, including a third party observer to control bias.
      Physicians reviewed major sections of an artificial but typical acute and chronic
      care visit note to identify the note sections that were relevant to their
      information needs. Statistical methods used were McNemar-Mosteller's and Cochran
      Q. RESULTS: Physicians identified History of Present Illness (HPI), Assessment,
      and Plan (A&P) as the most important sections of a visit note. In contrast, they
      largely judged the Review of Systems (ROS) to be superfluous. There was also a
      statistical difference in physicians' highlighting among all seven major note
      sections in acute (p = 0.00) and chronic (p = 0.00) care visit notes. CONCLUSION:
      A&P and HPI sections were most frequently identified as important which suggests
      that physicians may have to identify a few key sections out of a long,
      unnecessarily verbose visit note. ROS is viewed by doctors as mostly "not
      needed," but can have relevant information. The ROS can contain information
      needed for patient care when other sections of the Visit note, such as the HPI,
      lack the relevant information. Future studies should include producing a display
      that provides only relevant information to increase physician efficiency at the
      point of care. Also, research on moving A&P to the top of visit notes instead of
      having A&P at the bottom of the page is needed, since those are usually the first
      sections physicians refer to and reviewing from top to bottom may cause cognitive
      load.

PMID- 24734133
TI  - An information retrieval system for computerized patient records in the context
      of a daily hospital practice: the example of the Leon Berard Cancer Center
      (France).
AB  - BACKGROUND: A full-text search tool was introduced into the daily practice of
      Leon Berard Center (France), a health care facility devoted to treatment of
      cancer. This tool was integrated into the hospital information system by the IT
      department having been granted full autonomy to improve the system. OBJECTIVES:
      To describe the development and various uses of a tool for full-text search of
      computerized patient records. METHODS: The technology is based on Solr, an open
      source search engine. It is a web-based application that processes HTTP requests
      and returns HTTP responses. A data processing pipeline that retrieves data from
      different repositories, normalizes, cleans and publishes it to Solr, was
      integrated in the information system of the Leon Berard center. The IT department
      developed also user interfaces to allow users to access the search engine within
      the computerized medical record of the patient. RESULTS: From January to May
      2013, 500 queries were launched per month by an average of 140 different users.
      Several usages of the tool were described, as follows: medical management of
      patients, medical research, and improving the traceability of medical care in
      medical records. The sensitivity of the tool for detecting the medical records of
      patients diagnosed with both breast cancer and diabetes was 83.0%, and its
      positive predictive value was 48.7% (gold standard: manual screening by a
      clinical research assistant). CONCLUSION: The project demonstrates that the
      introduction of full-text-search tools allowed practitioners to use unstructured
      medical information for various purposes.

PMID- 24734134
TI  - Simulating adverse event spontaneous reporting systems as preferential attachment
      networks: application to the Vaccine Adverse Event Reporting System.
AB  - BACKGROUND: Spontaneous Reporting Systems [SRS] are critical tools in the post
      licensure evaluation of medical product safety. Regulatory authorities use a
      variety of data mining techniques to detect potential safety signals in SRS
      databases. Assessing the performance of such signal detection procedures requires
      simulated SRS databases, but simulation strategies proposed to date each have
      limitations. OBJECTIVE: We sought to develop a novel SRS simulation strategy
      based on plausible mechanisms for the growth of databases over time. METHODS: We
      developed a simulation strategy based on the network principle of preferential
      attachment. We demonstrated how this strategy can be used to create simulations
      based on specific databases of interest, and provided an example of using such
      simulations to compare signal detection thresholds for a popular data mining
      algorithm. RESULTS: The preferential attachment simulations were generally
      structurally similar to our targeted SRS database, although they had fewer nodes
      of very high degree. The approach was able to generate signal-free SRS
      simulations, as well as mimicking specific known true signals. Explorations of
      different reporting thresholds for the FDA Vaccine Adverse Event Reporting System
      suggested that using proportional reporting ratio [PRR] > 3.0 may yield better
      signal detection operating characteristics than the more commonly used PRR > 2.0
      threshold. DISCUSSION: The network analytic approach to SRS simulation based on
      the principle of preferential attachment provides an attractive framework for
      exploring the performance of safety signal detection algorithms. This approach is
      potentially more principled and versatile than existing simulation approaches.
      CONCLUSION: The utility of network-based SRS simulations needs to be further
      explored by evaluating other types of simulated signals with a broader range of
      data mining approaches, and comparing network-based simulations with other
      simulation strategies where applicable.

PMID- 24734135
TI  - Association between use of a health information exchange system and hospital
      admissions.
AB  - OBJECTIVE: Relevant patient information is frequently difficult to obtain in
      emergency department (ED) visits. Improved provider access to previously
      inaccessible patient information may improve the quality of care and reduce
      hospital admissions. Health information exchange (HIE) systems enable access to
      longitudinal, community-wide patient information at the point of care. However,
      the ability of HIE to avert admissions is not well demonstrated. We sought to
      determine if HIE system usage is correlated with a reduction in admissions via
      the ED. METHODS: We identified 15,645 adults from New York State with an ED visit
      during a 6-month period, all of whom consented to have their information
      accessible in the HIE system, and were continuously enrolled in two area health
      plans. Using claims we determined if the ED encounter resulted in an admission.
      We used the HIE's system log files to determine usage during the encounter. We
      determined the association between HIE system use and the likelihood of admission
      to the hospital from the ED and potential cost savings. RESULTS: The HIE system
      was accessed during 2.4% of encounters. The odds of an admission were 30% lower
      when the system was accessed after controlling for confounding (odds ratio =
      0.70; 95%C I= 0.52, 0.95). The annual savings in the sample was $357,000.
      CONCLUSION: These findings suggest that the use of an HIE system may reduce
      hospitalizations from the ED with resultant cost savings. This is an important
      outcome given the substantial financial investment in interventions designed to
      improve provider access to patient information in the US.

PMID- 24734136
TI  - Home blood pressure monitoring, secure electronic messaging and medication
      intensification for improving hypertension control: a mediation analysis.
AB  - OBJECTIVE: We evaluated the role of home monitoring, communication with
      pharmacists, medication intensification, medication adherence and lifestyle
      factors in contributing to the effectiveness of an intervention to improve blood
      pressure control in patients with uncontrolled essential hypertension. METHODS:
      We performed a mediation analysis of a published randomized trial based on the
      Chronic Care Model delivered over a secure patient website from June 2005 to
      December 2007. Study arms analyzed included usual care with a home blood pressure
      monitor and usual care with home blood pressure monitor and web-based pharmacist
      care. Mediator measures included secure messaging and telephone encounters; home
      blood pressure monitoring; medications intensification and adherence and
      lifestyle factors. Overall fidelity to the Chronic Care Model was assessed with
      the Patient Assessment of Chronic Care (PACIC) instrument. The primary outcome
      was percent of participants with blood pressure (BP) <140/90 mm Hg. RESULTS: At
      12 months follow-up, patients in the web-based pharmacist care group were more
      likely to have BP <140/90 mm Hg (55%) compared to patients in the group with home
      blood pressure monitors only (37%) (p = 0.001). Home blood pressure monitoring
      accounted for 30.3% of the intervention effect, secure electronic messaging
      accounted for 96%, and medication intensification for 29.3%. Medication adherence
      and self-report of fruit and vegetable intake and weight change were not
      different between the two study groups. The PACIC score accounted for 22.0 % of
      the main intervention effect. CONCLUSIONS: The effect of web-based pharmacist
      care on improved blood pressure control was explained in part through a
      combination of home blood pressure monitoring, secure messaging, and
      antihypertensive medication intensification.

PMID- 24734137
TI  - Text prediction on structured data entry in healthcare: a two-group randomized
      usability study measuring the prediction impact on user performance.
AB  - BACKGROUND: Structured data entry pervades computerized patient safety event
      reporting systems and serves as a key component in collecting patient-related
      information in electronic health records. Clinicians would spend more time being
      with patients and arrive at a high probability of proper diagnosis and treatment,
      if data entry can be completed efficiently and effectively. Historically it has
      been proven text prediction holds potential for human performance regarding data
      entry in a variety of research areas. OBJECTIVE: This study aimed at examining a
      function of text prediction proposed for increasing efficiency and data quality
      in structured data entry. METHODS: We employed a two-group randomized design with
      fifty-two nurses in this usability study. Each participant was assigned the task
      of reporting patient falls by answering multiple choice questions either with or
      without the text prediction function. t-test statistics and linear regression
      model were applied to analyzing the results of the two groups. RESULTS: While
      both groups of participants exhibited a good capacity of accomplishing the
      assigned task, the results were an overall 13.0% time reduction and 3.9% increase
      of response accuracy for the group utilizing the prediction function. CONCLUSION:
      As a primary attempt investigating the effectiveness of text prediction in
      healthcare, study findings validated the necessity of text prediction to
      structured date entry, and laid the ground for further research improving the
      effectiveness of text prediction in clinical settings.

PMID- 24734138
TI  - Design and multicentric implementation of a generic software architecture for
      patient recruitment systems re-using existing HIS tools and routine patient data.
AB  - OBJECTIVE: (1) To define features and data items of a Patient Recruitment System
      (PRS); (2) to design a generic software architecture of such a system covering
      the requirements; (3) to identify implementation options available within
      different Hospital Information System (HIS) environments; (4) to implement five
      PRS following the architecture and utilizing the implementation options as proof
      of concept. METHODS: Existing PRS were reviewed and interviews with users and
      developers conducted. All reported PRS features were collected and prioritized
      according to their published success and user's request. Common feature sets were
      combined into software modules of a generic software architecture. Data items to
      process and transfer were identified for each of the modules. Each site collected
      implementation options available within their respective HIS environment for each
      module, provided a prototypical implementation based on available implementation
      possibilities and supported the patient recruitment of a clinical trial as a
      proof of concept. RESULTS: 24 commonly reported and requested features of a PRS
      were identified, 13 of them prioritized as being mandatory. A UML version 2 based
      software architecture containing 5 software modules covering these features was
      developed. 13 data item groups processed by the modules, thus required to be
      available electronically, have been identified. Several implementation options
      could be identified for each module, most of them being available at multiple
      sites. Utilizing available tools, a PRS could be implemented in each of the five
      participating German university hospitals. CONCLUSION: A set of required features
      and data items of a PRS has been described for the first time. The software
      architecture covers all features in a clear, well-defined way. The variety of
      implementation options and the prototypes show that it is possible to implement
      the given architecture in different HIS environments, thus enabling more sites to
      successfully support patient recruitment in clinical trials.

PMID- 24734139
TI  - Using a scripted data entry process to transfer legacy immunization data while
      transitioning between electronic medical record systems.
AB  - BACKGROUND: Transitioning between Electronic Medical Records (EMR) can result in
      patient data being stranded in legacy systems with subsequent failure to provide
      appropriate patient care. Manual chart abstraction is labor intensive, error
      prone, and difficult to institute for immunizations on a systems level in a
      timely fashion. OBJECTIVES: We sought to transfer immunization data from two of
      our health system's soon to be replaced EMRs to the future EMR using a single
      process instead of separate interfaces for each facility. METHODS: We used
      scripted data entry, a process where a computer automates manual data entry, to
      insert data into the future EMR. Using the Center for Disease Control's CVX
      immunization codes we developed a bridge between immunization identifiers within
      our system's EMRs. We performed a two-step process evaluation of the data
      transfer using automated data comparison and manual chart review. RESULTS: We
      completed the data migration from two facilities in 16.8 hours with no data loss
      or corruption. We successfully populated the future EMR with 99.16% of our legacy
      immunization data - 500,906 records - just prior to our EMR transition date. A
      subset of immunizations, first recognized during clinical care, had not
      originally been extracted from the legacy systems. Once identified, this data -
      1,695 records - was migrated using the same process with minimal additional
      effort. CONCLUSIONS: Scripted data entry for immunizations is more accurate than
      published estimates for manual data entry and we completed our data transfer in
      1.2% of the total time we predicted for manual data entry. Performing this
      process before EMR conversion helped identify obstacles to data migration.
      Drawing upon this work, we will reuse this process for other healthcare
      facilities in our health system as they transition to the future EMR.

PMID- 24734140
TI  - An electronic alert for HIV screening in the emergency department increases
      screening but not the diagnosis of HIV.
AB  - OBJECTIVE: Based on US. Centers for Disease Control and Prevention
      recommendations, New York State enacted legislation in 2010 requiring healthcare
      providers to offer non-targeted human immunodeficiency virus (HIV) testing to all
      patients aged 13-64. Three New York City adult emergency departments implemented
      an electronic alert that required clinicians to document whether an HIV test was
      offered before discharging a patient. The purpose of this study was to assess the
      impact of the electronic alert on HIV testing rates and diagnosis of HIV positive
      individuals. METHODS: During the pre-intervention period (2.5-4 months), an
      electronic "HIV Testing" order set was available for clinicians to order a test
      or document a reason for not offering the test (e.g., patient is not conscious).
      An electronic alert was then added to enforce completion of the order set,
      effectively preventing ED discharge until an HIV test was offered to the patient.
      We analyzed data from 79,786 visits, measuring HIV testing and detection rates
      during the pre-intervention period and during the six months following the
      implementation of the alert. RESULTS: The percentage of visits where an HIV test
      was performed increased from 5.4% in the preintervention period to 8.7% (p<0.001)
      after the electronic alert. After the implementation of the electronic alert,
      there was a 61% increase in HIV tests performed per visit. However, the
      percentage of patients testing positive per total patients-tested was slightly
      lower in the post-intervention group than the pre-intervention group (0.48% vs.
      0.55%), but this was not significant. The number of patients-testing positive per
      total-patient visit was higher in the post-intervention group (0.04% vs. 0.03%).
      CONCLUSIONS: An electronic alert which enforced non-targeted screening was
      effective at increasing HIV testing rates but did not significantly increase the
      detection of persons living with HIV. The impact of this electronic alert on
      healthcare costs and quality of care merits further examination.

PMID- 24734141
TI  - Multidisciplinary approach to synchronous prostate and rectal cancer: current
      experience and future challenges.
AB  - The management of synchronous prostate and rectal cancer is a challeging task for
      the general surgeons and urologists, due to the complex anatomy of the pelvis and
      the sequential significant effects on the patient's functional independency and
      quality of life. As both rectal and prostate cancers still remain leading causes
      of death in the male population, along with the increase of the average life
      expectancy, it is certain that synchronous prostate and rectal cancer will be a
      clinical scenario that the clinicians of the future will encounter more
      frequently. Our aim is to perform a comprehensive review on the management of
      this oncological entity, focusing on the significance of multidisciplinary
      approach which will enable the formation of an accurate strategy plan, having at
      all times the patient in the center of desicion-making. 

PMID- 24734142
TI  - Researchers' and clinicians' perceptions of recruiting participants to clinical
      research: a thematic meta-synthesis.
AB  - BACKGROUND: Recruiting the desired number of research participants is frequently
      problematic with resulting financial and clinical implications. The views of
      individuals responsible for participant recruitment have not been previously
      reviewed. This systematic review and thematic meta-synthesis explores
      researchers' and clinicians' experiences and perceptions of recruiting
      participants to clinical research, with the aim of informing improved recruitment
      systems and strategies. METHODS: Studies published between January 1995 and May
      2013 were identified from: Ovid MEDLINE, Ovid EMBASE, Ovid PSYCHINFO, ASSIA,
      British Nursing Index, Scopus, Web of Science, CINAHL and PubMed. Included
      studies were original peer reviewed research, with qualitative methodologies and
      an aim of exploring the views of clinicians and/or researchers on recruitment to
      clinical research. Studies discussing the recruitment of patients unable to give
      informed consent were excluded. The findings sections of the relevant studies
      were free coded to identify key concepts which were grouped into hierarchical
      themes. The quality of the identified studies was assessed and the relative
      contribution of each paper was checked to ensure individual studies did not
      dominate in any theme. RESULTS: Eighteen relevant papers were identified which
      examined the views of researchers and clinicians in 10 clinical specialties. Five
      main themes emerged: building a research community, securing resources, the
      nature of research, professional identities and recruitment strategies. The views
      of researchers and clinicians were similar, although the role of 'researcher' was
      inconsistently defined. CONCLUSIONS: The general experience of recruiting
      participants to clinical research was one of competition and compromise.
      Competition arose over funding, staffing and participants, and between clinical
      and research responsibilities. Compromise was needed to create study designs that
      were acceptable to patients, clinicians and researchers. Forging relationships
      between clinical and research teams featured extensively, however the involvement
      of patients and the public within the research community was rarely discussed.

PMID- 24734143
TI  - The impact of a heart failure educational program for physicians varies based
      upon physician specialty.
AB  - BACKGROUND: Beta blocker (BB) doses are often suboptimal in heart failure (HF)
      management. Differences in BB management patterns may exist between physicians in
      family medicine (FM) and internal medicine (IM). The aims of this study were to
      compare: 1) BB doses and prescription patterns; and 2) health care utilization
      rates in patients cared for by all primary care physicians compared to an
      historical control group after an educational program on HF management. A
      subgroup analysis was performed between patients cared for by FM and IM
      physicians. A secondary aim was to assess physician knowledge scores and
      satisfaction. METHODS: A historically controlled study was conducted among low
      income, underserved HF patients (mean age 54.1 +/- 13.1, males 70%, mean ejection
      fraction 28.2 +/- 9.8%). Statistical methods included linear mixed models and
      Fisher's exact tests to assess prescription patterns of BB dosing and health care
      utilization rates (all cause and HF related hospitalizations, emergency
      department use and clinic visits). RESULTS: Among 135 patients (experimental N =
      81 and control N = 54), a linear mixed model test of group by time interaction
      showed no difference in BB dosage (t = -0.12, P = 0.91). FM physicians prescribed
      significant changes in BB doses compared to IM physicians (P = 0.04), had higher
      numbers of clinic visits (P = 0.03) and reported greater satisfaction with the
      program. CONCLUSIONS: There was no difference in BB titration rates following an
      HF training intervention for physicians compared to historical controls. However,
      FM physicians had a greater change in prescribing practices compared to IM
      physicians. Educational programs targeting FM physicians may benefit HF patients
      and could potentially lead to greater adherence to clinical guidelines related to
      BB use and address gaps in providing HF care.

PMID- 24734144
TI  - Exercise Profile and Diastolic Functions Measured via Tissue Doppler Imaging of
      Fibromyalgia Patients.
AB  - BACKGROUND: Our aim was to evaluate electrocardiographic and echocardiographic
      properties and exercise response of patients with fibromyalgia (FM). METHODS: The
      study included 60 women with primary FM and 30 healthy individuals. Resting
      electrocardiography, echocardiography and exercise treadmill test were used to
      compare these two groups. At apical four-chamber window, samples of transmitral
      diastolic inflow and tissue Doppler imaging of left ventricle lateral wall were
      obtained. Left ventricle ejection fraction was measured via modified Simpson's
      method. Exercise duration, maximal exercise capacity, maximal heart rate (HR)
      (bpm), maximal HR (%), rate-pressure product at maximal HR (bpm * mmHg), heart
      rate recovery 1 (bpm), heart rate recovery 2 (bpm) and chronotropic reserve (%)
      values were calculated. RESULTS: Resting HR and QTc values were similar in both
      groups. Echocardiographic measurements in both groups did not reveal
      statistically significant difference except left ventricle end-diastolic diameter
      and left atrial diameter. Parameters related to diastolic function of the left
      ventricle did not differ significantly in both groups. Also, there was not any
      significant difference between the groups for E/E' ratio and chronotropic
      reserve. Exercise treadmill test results were statistically similar for both
      groups. CONCLUSION: Patients with FM presented a normal HR response to exercise
      and those patients had normal diastolic function similar to their healthy
      controls.

PMID- 24734145
TI  - Value of twelfth hour bilirubin level in predicting significant
      hyperbilirubinemia in preterm infants.
AB  - BACKGROUND: As hyperbilirubinemia is a significant cause of brain injury, it is
      important to predict the cases who are at risk. Data for preterm infants are
      scarce. The aim of this study is to predict significant hyperbilirubinemia in
      preterm infants by measuring capillary bilirubin at 12th hour of life. METHODS:
      One hundred and fifty neonates born <= 35 weeks were included in the study. They
      were categorized into two groups according to their birth weights (group 1: 1,000
      - 1,499 g; group 2: 1,500 - 2,000 g). Their bilirubin levels were measured at
      12th hour and daily thereafter for 5 days. Risk nomograms were generated based on
      their bilirubin measurements and postnatal ages. On the age-specific percentile
      based nomogram, the zone above the 90th percentile was determined as high risk
      and those below the fifth percentile as low risk. Infants who had bilirubin
      levels over the limits defined according to their postnatal ages and birth
      weights were accepted to have significant hyperbilirubinemia and received
      phototherapy and predictive value of the 12th hour bilirubin was asssessed.
      RESULTS: Fifty-four of 57 infants (94.7%) in group 1 and 75/93 infants (80.7%) in
      group 2 received phototherapy. Capillary bilirubin levels of 3.55 mg/dL and 4.55
      mg/dL for group 1 and group 2 measured at the 12th hour of life had the highest
      sensitivity, negative and positive predictive value to predict the neonates who
      will develop significant hyperbilirubinemia. CONCLUSION: Bilirubin levels of
      preterm infants should be monitored closely. More attention should be paid to the
      ones who had 12th hour bilirubin level above the cutoff values.

PMID- 24734146
TI  - Knowledge levels regarding crimean-congo hemorrhagic Fever among emergency
      healthcare workers in an endemic region.
AB  - BACKGROUND: In this study, we aimed to determine knowledge levels regarding
      Crimean-Congo hemorrhagic fever (CCHF) among emergency healthcare workers (HCWs)
      in an endemic region. METHODS: A questionnaire form consisting of questions about
      CCHF was applied to the participants. RESULTS: The mean age was 29.6 +/- 6.5
      years (range 19 - 45). Fifty-four (49.5%) participants were physicians, 39
      (35.8%) were nurses and 16 (14.7%) were paramedics. All of the participants were
      aware of CCHF, and 48 (44%) of them had previously followed CCHF patients. Rates
      of the use of protective equipment (masks and gloves) during interventions for
      patients who were admitted to the emergency service with active hemorrhage were
      100% among paramedics, 76.9% among nurses and 61.1% among physicians (P = 0.003).
      Among 86 (78.9%) HCWs who believed that their knowledge regarding CCHF was
      adequate, 62 (56.9%) declared that they would prefer not to care for patients
      with CCHF (P = 0.608). CONCLUSIONS: The use of techniques to prevent transmission
      of this disease, including gloves, face masks, face visors and box coats, should
      be explained to emergency room HCWs, and encouragement should be provided for
      using these techniques.

PMID- 24734147
TI  - Informed consent for phase I oncology trials: form, substance and signature.
AB  - BACKGROUND: Federal regulations state consent information should be
      understandable to participants; concerns have been voiced about the quality of
      informed consent forms (ICFs) in oncology trials. METHODS: The content of ICFs
      for phase I studies that were conducted at a tertiary care cancer center over 3
      years' period was reviewed. Information pertaining to the length of the ICF,
      description of study purpose, research regimen/methods, treatment agent,
      potential risks, benefits and alternatives to the research was extracted.
      RESULTS: In total, 54 ICFs for phase I trials approved by the local Institutional
      Review Board were reviewed. Median length of ICF was 20 pages. Nearly one half of
      the forms (57.4%) were of first-in-human phase I studies. The main goal of
      research was explicitly stated as safety testing in 59.2% forms, while 37.1%
      studies described primary objective as dose finding. All of the forms identified
      serious risks, unexpected risks, possibility of death and risks to pregnant and
      or lactating women. A detailed estimation of the frequency or intensity of risks
      (range 3-8 pages) was provided qualitatively or quantitatively if known.
      Information regarding mechanism of action of investigational agent, study schema,
      dose escalation, loss of time/energy and possibility of receiving sub-therapeutic
      dose was missing in significant number of forms. CONCLUSION: We found that these
      ICFs were compliant with approved guidelines and provided a thorough description
      of risks or potential benefits. However, there still remains room for
      improvement, so patients can make better informed decisions.

PMID- 24734148
TI  - Non-invasive respiratory volume monitoring to detect apnea in post-operative
      patients: case series.
AB  - Obstructive sleep apnea (OSA) is a potential independent risk factor for
      postoperative complications, adverse surgical outcomes, and longer hospital
      stays. Obese patients with OSA have increased post-operative complications. An
      estimated 25-30% of pre-operative patients are at a high risk for OSA. A novel,
      non-invasive respiratory volume monitor (RVM) has been developed to provide a
      real time respiratory curve demonstrating lung volumes as well as a continuous,
      display of minute ventilation, tidal volume and respiratory rate. Clinical
      application of this device in the post-anesthesia care unit (PACU) can "unmask"
      post-operative apneic events resulting from partial or complete airway collapse
      due to the residual effects of narcotic administration and volatile and/or
      intravenous anesthetics. Clinical examples from two patients, one with known OSA
      and one without a previous diagnosis of OSA, monitored in the PACU with RVM are
      presented here. Post-operatively both patients had an increase in apneic episodes
      with significant decreases in their MV during apneic episodes after opioid
      administration as compared to pre-op baseline. In addition, oxygen saturation,
      for both patients, which is an essential component of current respiratory
      monitoring remained normal in the cases presented, despite the significant
      decreases in MV. Continuous RVM monitoring demonstrates both changes in
      respiratory patterns and overall adequacy of ventilation, and allows
      practitioners to quantify the increase in the number and duration apneic episodes
      as a response to narcotic administration. These case studies demonstrate that a
      non-invasive respiratory volume monitoring system can detect and quantify
      respiratory disturbances that currently go undetected. 

PMID- 24734149
TI  - Multifocal Cellulitis due to Disseminated Neisseria Gonorrhoeae in a Male
      Patient.
AB  - We report a rare case of disseminated gonococcal infection in a 37-year-old man
      presenting with multifocal cellulitis. The patient presented with fever and
      painful swelling of the right foot and left hand, and was admitted to our
      hospital. CT scanning of the extremities revealed multifocal cellulitis.
      Transthoracic echocardiography findings were normal, and piperacilin/tazoactam
      therapy was initiated. On antibiotic day 4, Neisseria gonorrhoeae was cultured
      from a purulent effusion collected from a focal site. Chlamydia trachomatis was
      detected in urine samples by PCR. We made the diagnosis of multifocal cellulitis
      due to N. gonorrhoeae in a patient with chlamydia urethritis. The antibiotic
      agent was changed from piperacilin/tazobactam to ceftriaxone. Levofloxacin was
      also administered for chlamydia urethritis. By admission day 14, all lesions had
      resolved and administration of antibiotic agents was terminated. Disseminated
      gonococcal infection, although rare, should be included in the differential
      diagnosis of all sexually active patients who present with multifocal cellulitis 
      also a rare condition, particularly in light of the fact that in recent times,
      patterns of sexual activity have changed, which was a pertinent factor in this
      case. 

PMID- 24734150
TI  - Chondrosarcoma of the proximal humerus secondary to ollier disease: an 8-year
      follow-up of successful resection of the tumor with endoprosthetic replacement of
      the proximal humerus.
AB  - We present a 25-year-old male patient with a diagnosis of multiple
      enchondromatosis, who developed chondrosarcoma on the proximal humerus of the
      right upper limb. The patient had the pre-existing lesions of Ollier's disease
      discovered during his childhood. The patient underwent wide resection of the
      sarcoma with a prosthetic replacement of the proximal humerus. So far we have
      followed up the patient for 8 years with no evidence of local recurrence and/or
      metastasis. The therapeutic results have been satisfied with a good functional
      recovery of the treated limb, enabling the patient to return to the pre-disease
      daily living and occupational activities. The reconstructive procedures represent
      an effective surgical strategy for limb salvage in the treatment of large
      segmental defects after resection of humeral tumors, substantially solving the
      functional and esthetic problems due to such a wide resection, and significantly
      improving the quality of life for the patient. 

PMID- 24734151
TI  - Primary prevention of colorectal neoplasias: ample evidence, lack of guidelines.

PMID- 24734152
TI  - In vitro antioxidant and cytotoxic activities of Arnebia benthamii (Wall ex. G.
      Don): a critically endangered medicinal plant of Kashmir Valley.
AB  - Arnebia benthamii is a major ingredient of the commercial drug available under
      the name Gaozaban, which has antibacterial, antifungal, anti-inflammatory, and
      wound-healing properties. In the present study, in vitro antioxidant and
      anticancer activity of different extracts of Arnebia benthamii were investigated.
      Antioxidant potential of plant extracts was evaluated by means of total
      phenolics, DPPH, reducing power, microsomal lipid peroxidation, and hydroxyl
      radical scavenging activity. The highest phenolic content (TPC) of 780 mg GAE/g
      was observed in ethyl acetate, while the lowest TPC of 462 mg GAE/g was achieved
      in aqueous extract. At concentration of 700 ug/mL, DPPH radical scavenging
      activity was found to be highest in ethyl acetate extract (87.99%) and lowest in
      aqueous extract (73%). The reducing power of extracts increased in a
      concentration dependent manner. We also observed its inhibition on
      Fe(2+)/ascorbic acid-induced lipid peroxidation (LPO) on rat liver microsomes in
      vitro. In addition, Arnebia benthamii extracts exhibited antioxidant effects on
      Calf thymus DNA damage induced by Fenton reaction. Cytotoxicity of the extracts
      (10-100 ug/mL) was tested on five human cancer cell lines (lung, prostate,
      leukemia, colon, and pancreatic cell lines) using the Sulphorhodamine B assay.

PMID- 24734153
TI  - Cardiovascular complications of sleep apnea: role of oxidative stress.
AB  - Obstructive sleep apnea (OSA) occurs in 2% of middle-aged women and 4% of middle
      aged men with a higher prevalence among obese subjects. This condition is
      considered as an independent risk factor for cerebrovascular and cardiovascular
      diseases. One of the major pathophysiological characteristics of OSA is
      intermittent hypoxia. Hypoxia can lead to oxidative stress and overproduction of
      reactive oxygen species, which can lead to endothelial dysfunction, a hallmark of
      atherosclerosis. Many animal models, such as the rodent model of intermittent
      hypoxia, mimic obstructive sleep apnea in human patients and allow more in-depth
      investigation of biological and cellular mechanisms of this condition. This
      review discusses the role of oxidative stress in cardiovascular disease resulting
      from OSA in humans and animal models. 

PMID- 24734156
TI  - Relationship between ABO blood group and Acute Lymphoblastic Leukemia.
AB  - Acute lymphoblastic leukemia (ALL) constitute a family of genetically
      heterogeneous lymphoid neoplasms derived from B- and T-lymphoid progenitors. ALL
      affects both children and adults. Diagnosis is based on morphologic,
      immunophenotypic, and genetic features that allow differentiation from normal
      progenitors and other hematopoietic and nonhematopoietic neoplasms. The aim of
      this study was to investigate the association between ALL and ABO blood group.
      MATERIAL AND METHOD: This is a case-control study that was carried out in Amir
      Oncology Hospital in Shiraz during 2011 to2013. The case group consisted of 293
      patients with acute lymphoblastic leukemia. And compared with 300 subject in
      control group ( the age in the case group was between 2-5 year, and the age in
      the control group was between 2-45 year) .Statistical analyzes was done performed
      by chi -square test. The results was considered significant when p value <0.05.
      (CI:0.95). RESULTS: The ABO blood group distribution was 82(A), 59 (B), 24 (AB)
      and 128(O) in patient with Acute Lymphoblastic Leukemia and the blood group of
      300 participants in the control group include, 63% (25) A, 69% (25.6) B, 18 %
      06.8) AB and 101% (42.6) O. The ABO blood group distribution showed that there is
      significant differences between ABO blood group and patients with acute
      lymphoblastic leukemia . CONCLUSION: This study showed significant association
      between ALL and ABO blood group and showed that blood group AB was associated
      with a higher risk of All (p value<0.001).

PMID- 24734154
TI  - Use of blood-based biomarkers for early diagnosis and surveillance of colorectal
      cancer.
AB  - Early screening for colorectal cancer (CRC) holds the key to combat and control
      the increasing global burden of CRC morbidity and mortality. However, the current
      available screening modalities are severely inadequate because of their high cost
      and cumbersome preparatory procedures that ultimately lead to a low participation
      rate. People simply do not like to have colonoscopies. It would be ideal,
      therefore, to develop an alternative modality based on blood biomarkers as the
      first line screening test. This will allow for the differentiation of the general
      population from high risk individuals. Colonoscopy would then become the
      secondary test, to further screen the high risk segment of the population. This
      will encourage participation and therefore help to reach the goal of early
      detection and thereby reduce the anticipated increasing global CRC incidence
      rate. A blood-based screening test is an appealing alternative as it is non
      invasive and poses minimal risk to patients. It is easy to perform, can be
      repeated at shorter intervals, and therefore would likely lead to a much higher
      participation rate. This review surveys various blood-based test strategies
      currently under investigation, discusses the potency of what is available, and
      assesses how new technology may contribute to future test design. 

PMID- 24734157
TI  - Prevalence of transient hyperglycemia and diabetes mellitus in pediatric patients
      with acute leukemia.
AB  - BACKGROUND: The most common malignancy of children is Leukemia, accounting
      approximately one third of cancer diagnosis. Available data demonstrate
      improvement in survival of pediatric leukemia, so evaluation of side effects of
      treatment is very important. This study investigates hyperglycemia and diabetes
      mellitus prevalence in pediatric patients with acute leukemia. MATERIALS AND
      METHODS: This study was performed in children with acute leukemia. At the first
      admission, demographic data was collected and blood glucose and HbA1c levels were
      obtained. These tests examined at least two times during six months of follow up.
      Growth parameters and blood samples were obtained too. RESULT: Twenty nine
      patients were examined; three of them (10.3%) had diabetes mellitus and 5patients
      (17.2%) had transient hyperglycemia.Mean age of the patients was 6.26 years and
      nineteen Children (63%) were in preschool age. In preschool age children,
      incidence of hyperglycemia was meaningfully higher than school age children (p=
      0.02). 24 of 29 patients (82.7%) were known case of acute lymphoblastic leukemia
      (ALL) and 5 patients (17.3%) were known case of acute myeloblastic leukemia
      (AML). No significant difference was found between sex groups. Also underweight
      was significant risk factor for hyperglycemia. CONCLUSION: The prevalence of
      hyperglycemia was in the range of other similar studies in different parts of the
      world. Underweight and preschool ages were significant predictors of
      hyperglycemia.

PMID- 24734155
TI  - Colorectal carcinoma in a Southern Mediterranean country: The Libyan scenario.
AB  - AIM: To study the salient features of colorectal cancer (CRC) in Libya. METHODS:
      Patients records were gathered at the primary oncology clinic in eastern Libya
      for the period of one calendar year (2012). Using this data, various parameters
      were analyzed and age-standardized incidence rates were determined using the
      direct method and the standard population. RESULTS: During 2012, 174 patients
      were diagnosed with CRC, 51.7% (n = 90) male and 48.3% (n = 84) females. The
      average age was 58.7 (+/- 13.4) years, with men around 57.3 (+/- 13) years old
      and women usually 60.1 (+/- 13.8) years of age. Libya has the highest rate of CRC
      in North Africa, with an incidence closer to the European figures. The age
      standardized rate for CRC was 17.5 and 17.2/100000 for males and females
      respectively. It was the second most common cancer, forming 19% of malignancies,
      with fluctuation in ranking and incidence in different cities/villages.
      Increasingly, younger ages are being afflicted and a higher proportion of
      patients are among the > 40 years subset. Nearly two-thirds presented at either
      stage III (22.4%) or IV (38.4%). CONCLUSION: Cancer surveillance systems should
      be established in order to effectively monitor the situation. Likewise, screening
      programs are invaluable in the Libyan scenario given the predominance of sporadic
      cases.

PMID- 24734158
TI  - Comparison of two iron supplementation methods on Hemoglobin level and Menstrual
      Bleeding in Tabriz students.
AB  - BACKGROUND: Iron deficiency anemia is a global health problem, and approximately
      50% of anemia is caused by iron deficiency. According to studies, iron
      supplementation in young females improves iron status by increasing concentration
      of hemoglobin. To compare of prescribing two methods of iron supplementation
      administered either on a weekly basis or during menstruation, on hemoglobin level
      and menstrual blood  this double blind Randomized clinical trial study was
      carried out among female students in Tabriz, Iran. MATERIALS AND METHODS: In this
      double-blind randomized clinical trial, 150 female students allocated randomly in
      two groups. (75 students took an iron tablet weekly and 75 students took an iron
      tablet for first four days during their menstruation cycle for 16 weeks). Before
      and after intervention, the level of hemoglobin was measured and Higham chart was
      completed by participants in each group. Chi-square, independent t-Test, paired t
      Test and ANCOVA were used for data analysis. RESULTS: There was no significant
      difference between two groups in terms of demographic characteristics, hemoglobin
      level and amount of menstrual bleeding before and after intervention (p>0.05).
      Taking iron supplement increased significantly the level of hemoglobin in each
      group (p<0.001). However, there was no significant difference in amount of
      menstrual bleeding (p>0.05) when comparing the data before and after intervention
      in each group. CONCLUSION: The two iron supplementation methods (menstrual
      bleeding period and weekly) have similar results on Hemoglobin level and
      menstrual bleeding.

PMID- 24734159
TI  - Association between serum ferritin level, cardiac and hepatic T2-star MRI in
      patients with major beta-thalassemia.
AB  - BACKGROUND: Frequent blood transfusion is often associated with iron overload.
      Proper use of iron chelators to treat iron overload requires an accurate
      measurement of iron levels. Magnetic resonance T2-star (T2* MRI) can measure iron
      level in the heart and liver. Our goal was to see whether an association exists
      between serum ferritin level and T2* MRI in patients with major beta thalassemia.
      MATERIALS AND METHODS: Sixty patients with a diagnosis of major beta thalassemia
      were enrolled in the study. They were older than five years old and needed
      regular transfusion. Cardiac and hepatic T2*MRI and mean serum ferritin levels
      were measured within 3 months. RESULTS: No significant correlation was observed
      between serum ferritin level and cardiac T2*MRI (p=0.361, r=-0.120).However, a
      significant correlation was observed between serum ferritin and liver T2*MRI
      (p=0.021, r=-0.297). CONCLUSION: Our results showed an association between
      hepatic T2*MRI and serum ferritin level.

PMID- 24734160
TI  - Toxoplasmosis as a complication of transfusion in hemodialysis patients.
AB  - BACKGROUND: Toxoplasma Gondi is an obligate intracellular protozoan parasite that
      is one of the most important protozoa of blood and tissue. The medical importance
      of this parasite is considered from two aspects of congenital defects and
      opportunities among those with congenital immune deficiency. Depending on the
      mode of transmission through blood and the risk of infection to Toxoplasma Gondi
      in hemodialysis patients, this serological study was conducted on Iranian
      population. MATERIALS AND METHODS: This case-control study was conducted on 37
      patients that underwent regular hemodialysis that 21 were male and 16 were
      female, and the mean age of them was 17.52+/-4.10 years (rages 13-22 years).
      Thirty-seven healthy individuals were chosen as control group. All samples were
      tested by using of ELISA kits with two methods of IgG-ELISA and IgM-ELISA.
      Finally obtained data was analysis by SPSS software. RESULTS: The results of this
      study revealed high prevalence of toxoplasmosis among hemodialysis patients.
      Other findings indicate that 21 out of 37 patients in the case group were
      positive for anti-Toxoplasma Gondi IgG in case group while in control group just
      11 individuals were positive that was a statistically significant difference(p
      <0.05 ). CONCLUSION: because of the high prevalence of toxoplasmosis among
      hemodialysis patients, identification of these patients for prevention of
      transfusion complications is important.

PMID- 24734161
TI  - Family screening for a novel ATP7B gene mutation, c.2335T>G, in the South of
      Iran.
AB  - BACKGROUND: Wilson disease (WD) is a rare autosomal recessive disorder, which
      leads to copper metabolism, due to mutations in ATP7B gene. The gene responsible
      for WD consists of 21 exons that span a genomic region of about 80 kb and encodes
      a copper transporting P-type ATPase (ATP7B), a protein consisting of 1465 amino
      acids. Identifying mutation in ATP7B gene is important to find carrier
      individuals for proper counseling. A novel mutation in exon 8 of ATP7B gene,
      c.2335T>G (p.Trp779Gly), with severe neuropsychiatric condition in the South of
      Iran, was recently identified. The aim of this study was to screen 120
      individuals from a large family using a simple amplification refractory mutation
      system PCR (ARMS-PCR) for carrier screening in the South of Iran. MATERIALS AND
      METHODS: 120 individuals from family relatives of an index case in the Nasr Abad,
      south of Iran, were studied for screening of the c.2335T>G mutation. One patient
      with homozygous mutation and one homozygous normal individual were used as
      controls in this experiment. RESULTS: Altogether, 16 out of 120 (13.3%)
      individuals within this region had heterozygous mutation. One individual with
      homozygote mutation was also identified. CONCLUSION: Identification of carriers
      in families with affected individuals is of great importance for counseling
      before marriage. The results of this study can be used for further counseling
      programs in this population.

PMID- 24734162
TI  - Assessment of Thiopurine-based drugs according to Thiopurine S-methyltransferase
      genotype in patients with Acute Lymphoblastic Leukemia.
AB  - For the past half century, thiopurines have earned themselves a reputation as
      effective anti-cancer and immunosuppressive drugs. Thiopurine S-methyltransferase
      (TPMT) is involved in the metabolism of all thiopurines and is one of the main
      enzymes that inactivates mercaptopurine. 6-MP is now used as a combination
      therapies for maintenance therapy of children with acute lymphocytic leukemia
      (ALL). In all patients receiving mercaptopurine, there is a risk of bone marrow
      suppression. TPMT activity is inherited as a monogenic, co-dominant trait. More
      than 25 variants are known. Genetic testing is available for several TPMT variant
      alleles. Most commonly TPMT*2, *3A, and *3C are tested for, which account for
      >90% of inactivating alleles. Differences in DNA that alter the expression or
      function of proteins that are targeted by drugs can contribute significantly to
      variation in the responses of individuals.Genotyping may become part of routine
      investigations to help clinicians tailor drug treatment effectively. This success
      is mainly due to the development of combination therapies and stratification of
      patients according to risk of treatment failure and relapse, rather than the
      discovery of new drugs. The aim of this study was to investigate the effect of
      genotype or methyltransferase enzyme activity before starting therapy in children
      with ALL. This can prevent the side effect of thiopurine drugs. In fact, the
      common polymorphism of this enzyme in population could be a prognostic factor in
      relation to drug use and treatment of patients with ALL. 

PMID- 24734163
TI  - Mosaic and partial monosomy of chromosome 21 in a case with low platelets count.
AB  - BACKGROUND: Monosomy is defined as the presence of only one chromosome instead of
      two in humans. Partial monosomy occurs when only a portion of the chromosome is
      present in a single copy, while the rest has two copies. It can occur in
      unbalanced translocations or deletions. CASE REPORT: In this report, a 6 years
      old girl was presented who was referred to the Pediatric Dep, Shahid Sadoughi
      Hospital,Yazd, Iran, due to multiple congenital anomalies such as: frontal
      bossing, horizontal palpebral fissure, small deepest eyes, aplastic nasal bridge,
      broad philtrum, low set ears, large prominent ears, short neck, microcephaly,
      pectus excavatum, mental retardation, and dislocation of the hip. In peripheral
      blood smear, platelets were decreased but other hematological levels were normal.
      The karyotype result indicated a mosaic monosomy and partial monosomy of
      chromosome 21. CONCLUSION: According to this and other case reports of monosomy
      of chromosome 21, this disease had very low prevalence rate among live infants or
      children. The present case had some congenital anomalies that present with
      abnormal medical condition. Therefore these patients must be evaluated for
      chromosomal studies.

PMID- 24734164
TI  - Establishment of reference standards in biosimilar studies.
AB  - When an innovative biological product goes off-patent, biopharmaceutical or
      biotechnological companies may file an application for regulatory approval of
      biosimilar products. In practice, however, important information on the
      innovative (reference) product may not be available for assessment. Thus, it is
      important to first establish a reference standard while assessing biosimilarity
      between a biosimilar product and the reference product. In this paper, reference
      standard is established through the biosimilarity index approach based on a
      reference-replicated study (or R-R study), in which the reference product is
      compared with itself under various scenarios. The reference standard can then be
      used for assessing the degree of similarity between the test and reference drugs
      in biosimilar studies.

PMID- 24734165
TI  - Developmental neurotoxicity of alcohol and anesthetic drugs is augmented by co
      exposure to caffeine.
AB  - Anesthetic and anti-epileptic drugs used in pediatric and obstetric medicine and
      several drugs, including alcohol, that are abused by pregnant women, trigger
      widespread neuroapoptosis in the developing brain of several animal species,
      including non-human primates. Caffeine (CAF) is often administered to premature
      infants to stimulate respiration, and these infants are also exposed
      simultaneously to anesthetic drugs for procedural sedation and/or surgical
      procedures. Pregnant women who abuse alcohol or other apoptogenic drugs also may
      heavily consume CAF. We administered CAF to infant mice alone or in combination
      with alcohol, phencyclidine, diazepam, midazolam, ketamine, or isoflurane, which
      are drugs of abuse and/or drugs frequently used in pediatric medicine, and found
      that CAF weakly triggers neuroapoptosis by itself and markedly potentiates the
      neuroapoptogenic action of each of these other drugs. Exposure of infant mice to
      CAF + phencyclidine resulted in long-term impairment in behavioral domains
      relevant to attention deficit/hyperactivity disorder, whereas exposure to CAF +
      diazepam resulted in long-term learning/memory impairment. At doses used in these
      experiments, these behavioral impairments either did not occur or were
      substantially less pronounced in mice exposed to CAF alone or to phencyclidine or
      diazepam alone. CAF currently enjoys the reputation of being highly beneficial
      and safe for use in neonatal medicine. Our data suggest the need to consider
      whether CAF may have harmful as well as beneficial effects on the developing
      brain, and the need for research aimed at understanding the full advantage of its
      beneficial effects while avoiding its potentially harmful effects. 

PMID- 24734166
TI  - Gender differences in vogt-koyanagi-harada disease and sympathetic ophthalmia.
AB  - Vogt-Koyanagi-Harada disease (VKH) and sympathetic ophthalmia (SO) are types of T
      cell mediated autoimmune granulomatous uveitis. Although the two diseases share
      common clinical features, they have certain differences in gender predilections.
      VKH classically has been reported as more prevalent in females than males, yet
      some studies in Japan and China have not found differences in gender prevalence.
      Male patients have a higher risk of chorioretinal degeneration, vitiligo, and
      worse prognosis. Conversely, the changing levels of estrogen/progesterone during
      pregnancy and the menstrual cycle as well as higher levels of TGF-beta show a
      protective role in females. Potential causes of female predilection for VKH are
      associated with HLA-DR and HLA-DQ alleles. SO, a bilateral granulomatous uveitis,
      occurs in the context of one eye after a penetrating injury due to trauma or
      surgery. In contrast to the female dominance in VKH, males are more frequently
      affected by SO due to a higher incidence of ocular injury, especially during
      wartime. However, no gender predilection of SO has been reported in postsurgical
      cases. No clinically different manifestations are revealed between males and
      females in SO secondary to either ocular trauma or surgery. The potential causes
      of the gender difference may provide hints on future treatment and disease
      evaluation. 

PMID- 24734167
TI  - Age-matched, case-controlled comparison of clinical indicators for development of
      entropion and ectropion.
AB  - Purpose. To analyze the clinical findings associated with involutional entropion
      and ectropion and compare them to each other and to age-matched controls.
      Methods. Prospective, age-matched cohort study involving 30 lids with
      involutional entropion, 30 lids with involutional ectropion, and 52 age-matched
      control lids. Results. The statistically significant differences associated with
      both the entropion and ectropion groups compared to the control group were
      presence of a retractor dehiscence, presence of a "white line," occurrence of
      orbital fat prolapse in the cul-de-sac, decreased lower lid excursion, increased
      lid laxity by the snapback test, and an increased lower lid distraction.
      Entropion also differed from the control group with an increased lid crease
      height and decreased lateral canthal excursion. Statistically significant
      differences associated with entropion compared to ectropion were presence of a
      retractor dehiscence, decreased lateral canthal excursion, and less laxity in the
      snapback test. Conclusion. Entropic and ectropic lids demonstrate clinically and
      statistically significant anatomical and functional differences from normal, age
      matched lids. Many clinical findings associated with entropion are also present
      in ectropion. Entropion is more likely to develop with a pronounced retractor
      deficiency. Ectropion is more likely to develop with diminished elasticity as
      measured by the snapback test. 

PMID- 24734168
TI  - Corneal backscatter analysis by in vivo confocal microscopy: fellow eye
      comparison of small incision lenticule extraction and femtosecond laser-assisted
      LASIK.
AB  - Purpose. To evaluate and compare corneal backscatter from anterior stroma between
      small incision lenticule extraction (SMILE) and femtosecond laser-assisted LASIK
      (femto-LASIK). Methods. A cohort of 60 eyes of 30 patients was randomized to
      receive SMILE in one eye and femto-LASIK in the fellow eye. In vivo confocal
      microscopy was performed at 1 week and 1, 3, and 6 months after surgery. The main
      outcome measurements were maximum backscattered intensity and the depth from
      which it was measured, the backscattered light intensity 30  MU m below Bowman's
      membrane at the flap interface and 150  MU m below the superficial epithelium,
      and the number of refractive particles at the flap interface. Results. The mean
      backscattered light intensity (LI) at all measured depths and the maximum
      backscattered LI were higher in the SMILE group than the femto-LASIK group at all
      postoperative visits. LI differences at 1 week and 1- and 3-month visits were
      statistically significant (P < 0,05). LI differences at 6 months were not
      statistically significant. There was no difference in the number of refractive
      particles at the flap interface between the groups at any visit. Conclusions.
      SMILE results in increased backscattered LI in the anterior stroma when compared
      with femto-LASIK were evaluated. 

PMID- 24734169
TI  - Solitary sarcoid granuloma of the iris mimicking tuberculosis: a case report.
AB  - Introduction. We report a case of a male patient presented with sarcoid lesions
      of the iris and conjunctiva, mimicking tuberculosis due to epithelioid cell
      granulomas with small central necrosis in conjunctival biopsy. Patient. A 25-year
      old man was referred to our department for further management of an "iris tumor
      with iridocyclitis" in his right eye. Initial examination showed an isolated
      vascular tumor of the iris and ciliary body with anterior uveitis and mutton-fat
      keratic precipitates, suggesting the diagnosis of a granulomatous disease.
      Conjunctival biopsy revealed granulomatous epithelioid cell inflammation with
      small central necrosis without acid-fast bacilli. Extensive systemic examination,
      including bronchoscopy and transbronchial biopsy, provided the diagnosis of
      sarcoidosis stage 2 with pulmonary involvement, thus ruling out tuberculosis.
      Systemic and local steroid therapy was initiated, leading to complete recovery of
      our patient with complete disappearance of the iris lesion and improvement of the
      pulmonary function. Conclusion. Although noncaseating epithelioid cell granulomas
      are typical for sarcoidosis, small central necrosis can be found in some
      granulomas, leading to presumption of tuberculosis. Extensive systemic checkup in
      cooperation with other specialists is essential to confirm the correct diagnosis
      and to initiate the appropriate therapy. 

PMID- 24734170
TI  - Intravitreal and subconjunctival melphalan for retinoblastoma in transgenic mice.
AB  - Purpose. To measure the chemotherapeutic effects of focal melphalan (intravitreal
      and subconjunctival) on tumor burden, hypoxia, and vasculature in LHBETATAG
      murine retinoblastoma model. Methods. LHBETATAG transgenic mice were treated with
      a single 1 mcg intravitreal injection of melphalan, 100 mcg subconjunctival
      injection, or semiweekly 10 mcg subconjunctival injections for 3 weeks. At 1 or 3
      weeks, eyes were enucleated, serially sectioned, and processed with haematoxylin
      and eosin (H&E) for tumor burden measurements and probed with immunofluorescence
      to analyze tumor hypoxia and vasculature. Results. Focal melphalan significantly
      reduced retinal tumor size (P < 0.02) when given intravitreally or
      subconjunctivally. Eyes treated with a one-time intravitreal injection of 1 mcg
      melphalan had significantly smaller tumors at both 1 week (P = 0.017) and at 3
      weeks after injection (P = 0.005). Intratumoral hypoxia showed a significant
      decline in hypoxia at 1 week following intravitreal injection and after maximum
      dosage of subconjunctival melphalan. Total vasculature was not significantly
      affected following intravitreal administration. Conclusion. Focal delivery of
      melphalan via intravitreal or subconjunctival injection has a significant effect
      on reducing tumor burden, hypoxia, and vasculature, in the treatment of murine
      retinoblastoma tumors. 

PMID- 24734171
TI  - Comparison of latanoprost/timolol with carbonic anhydrase inhibitor and
      dorzolamide/timolol with prostaglandin analog in the treatment of glaucoma.
AB  - Purpose. We retrospectively reviewed medical records of glaucoma patients to
      investigate how switching medications may affect intraocular pressure (IOP)
      management. Three concomitant medications were changed to two medications: one
      combination drop and one single-action drop. Associated adverse effects were also
      examined. Subjects and Methods. A total of 112 patients with primary open-angle
      glaucoma or ocular hypertension were examined. All patients were concomitantly
      using a prostaglandin (PG) analog, a beta -blocker, and a carbonic anhydrate
      inhibitor (CAI). Fifty-five patients began using latanoprost (PG analog)/timolol
      ( beta -blocker) fixed-combination (LTFC) drops and a CAI (group 1), and 57
      patients began using dorzolamide (CAI)/timolol fixed-combination (DTFC) drops and
      a PG analog (group 2). The IOP was measured every 6 months for 2 years following
      medication changes. Changes in visual field mean deviation (MD) and medication
      discontinuations were also examined. Results. There were no significant
      differences in IOP or MD values before and after medication changes in either
      group. The proportion of medication discontinuations, uncontrolled IOP, and
      adverse reactions was similar in both groups. Conclusion. Switching patients from
      multiple single-action medications to combination medications was not associated
      with changes in IOP, visual field testing results, or adverse event frequency. 

PMID- 24734172
TI  - Prolonged Laccase Production by a Cold and pH Tolerant Strain of Penicillium
      pinophilum (MCC 1049) Isolated from a Low Temperature Environment.
AB  - Production of laccase by a cold and pH tolerant strain of Penicillium pinophilum
      has been investigated under different cultural conditions for up to 35 days of
      incubation. The fungus was originally isolated from a low temperature environment
      under mountain ecosystem of Indian Himalaya. The estimations were conducted at 3
      temperatures (15, 25, and 35 degrees C), a range of pH (3.5-11.5), and in
      presence of supplements including carbon and nitrogen sources, vitamins, and
      antibiotics. Optimum production of laccase was recorded at 25 degrees C (optimum
      temperature for fungal growth) and 7.5 pH. The production of enzyme was recorded
      maximum on day 28 (11.6 +/- 0.52 U/L) following a slow decline at day 35 of
      incubation (10.6 +/- 0.80 U/L). Fructose and potassium nitrate (0.2%) among
      nutritional supplements, chloramphenicol (0.1%) among antibiotics, and folic acid
      (0.1%) among vitamins were found to be the best enhancers for production of
      laccase. Relatively lower but consistent production of laccase for a longer
      period is likely to be an ecologically important phenomenon under low temperature
      environment. Further, enhancement in production of enzyme using various
      supplements will be useful for its use in specific biotechnological applications.

PMID- 24734173
TI  - Role of hla-B alleles and clinical presentation of b27 negative spondyloarthritis
      patients from mumbai, Western India.
AB  - Seronegative spondyloarthritis (SpA) are variably associated with HLA-B*27
      antigen. HLA-B*27 negative SpA has also been reported from different parts of the
      world. There is paucity of data on this entity from Indian subcontinent. We
      studied 100 consecutively diagnosed HLA-B27 negative spondyloarthritis patients
      from a tertiary care center in India. Modified New York Criteria for ankylosing
      spondylitis (AS) and ESSG criteria for SpA were used for diagnosing patients. HLA
      B*27 typing was done by an in-house PCR-SSP technique in SpA patients to exclude
      B*27 positive patients and PCR-SSOP technique was used to type 100 B*27 negative
      SpA patients and 100 controls from the same ethnicity. Frequency of B*07 was
      significantly increased (B*07: % PF 54 versus 18; OR 5.348; 95% CI 2.808-10.186;
      P value 1.14E - 07), whereas frequency of B*40 was significantly decreased (B*40:
      % PF 17 versus 32; OR 0.435; 95% CI 0.222-0.850; P value 0.013) when compared
      with B*27 negative controls. Among 100 SpA patients, 47 were undifferentiated
      spondyloarthritis and 33 patients were reactive arthritis patients. 40% of the
      patients were suffering from polyarticular arthritis, 35% had pauciarticular
      arthritis with knee joint, hip joint, ankle joint, and SI joint involvement. We
      conclude that B*07 was significantly associated with B27 negative
      spondyloarthropathy from Western India and majority of B*27 negative patients
      were uSpA. 

PMID- 24734174
TI  - The facial affective scale as a predictor for pain unpleasantness when children
      undergo immunizations.
AB  - Needle fear is a common problem in children undergoing immunization. To ensure
      that the individual child's needs are met during a painful procedure it would be
      beneficial to be able to predict whether there is a need for extra support. The
      self-reporting instrument facial affective scale (FAS) could have potential for
      this purpose. The aim of this study was to evaluate whether the FAS can predict
      pain unpleasantness in girls undergoing immunization. Girls, aged 11-12 years,
      reported their expected pain unpleasantness on the FAS at least two weeks before
      and then experienced pain unpleasantness immediately before each vaccination. The
      experienced pain unpleasantness during the vaccination was also reported
      immediately after each immunization. The level of anxiety was similarly assessed
      during each vaccination and supplemented with stress measures in relation to the
      procedure in order to assess and evaluate concurrent validity. The results show
      that the FAS is valid to predict pain unpleasantness in 11-12-year-old girls who
      undergo immunizations and that it has the potential to be a feasible instrument
      to identify children who are in need of extra support to cope with immunization.
      In conclusion, the FAS measurement can facilitate caring interventions. 

PMID- 24734175
TI  - How do older persons understand the purpose and relevance of preventive home
      visits? A study of experiences after a first visit.
AB  - The aim of this study was to explore and describe older persons' experiences of
      their first Preventive Home Visit. Preventive Home Visits (PHV) are health
      services that aim to promote older persons' health, prevent functional decline,
      and reduce the need for comprehensive healthcare. The knowledge base to guide the
      design of effective PHV interventions is scarce. Studies that explore older
      persons' experiences of the first visit are essential, as compliance with the
      service is a prerequisite for positive outcomes. An explorative and descriptive
      design was applied. Qualitative research interviews with ten older persons who
      had received the first PHV the previous year were analysed with regard to
      manifest and latent content. The findings revealed that the understanding of the
      purpose of PHV varied. For some participants, the concepts and aims of health
      promotion and disease prevention were difficult to comprehend. The possibility to
      prepare for the visit was sought. All participants appreciated the service; the
      dialogue quality was good and a trusted municipal contact person provided
      security. To enhance compliance and ensure effective PHV, the invitation to the
      PHV service should include clearly stated aims and specific information about the
      first visit. An individualised, person-centred approach should be applied. 

PMID- 24734176
TI  - Factors influencing early health facility contact and low default rate among new
      sputum smear positive tuberculosis patients, India.
AB  - Early case identification and prompt treatment of new sputum smear positive case
      are important to reduce the spread of tuberculosis (TB). Present study was
      planned to study the associated factors for duration to contact the health
      facility since appearance of symptoms and treatment default. Methodology. It was
      prospective cohort study of TB patients already registered for treatment in
      randomly selected TB units (TUs) in Himachal Pradesh, India. Relative risk (RR)
      was calculated as risk estimate to find out the explanatory variables for early
      contact and default. Results. Total 1607 patients were recruited and 25 (1.5%)
      defaulted treatment. Patients from nuclear family (aRR: 1.37; 1.09-1.73), ashamed
      of TB (aRR: 1.32; 1.03-1.70), wishing to disclose disease status (aRR: 1.79; 1.43
      2.24), but aware of curable nature (aRR: 1.67; 1.17-2.39) and preventable (aRR:
      1.35; 1.07-1.70) nature of disease, contacted health facility early since
      appearance of symptoms. Conclusion. Better awareness and less misconceptions
      about disease influences the early contact of health facility and low default
      rate in North India. 

PMID- 24734178
TI  - An update on coronary artery disease and chronic kidney disease.
AB  - Despite the improvements in diagnostic tools and medical applications,
      cardiovascular diseases (CVD), especially coronary artery disease (CAD), remain
      the most common cause of morbidity and mortality in patients with chronic kidney
      disease (CKD). The main factors for the heightened risk in this population,
      beside advanced age and a high proportion of diabetes and hypertension, are
      malnutrition, chronic inflammation, accelerated atherosclerosis, endothelial
      dysfunction, coronary artery calcification, left ventricular structural and
      functional abnormalities, and bone mineral disorders. Chronic kidney disease is
      now recognized as an independent risk factor for CAD. In community-based studies,
      decreased glomerular filtration rate (GFR) and proteinuria were both found to be
      independently associated with CAD. This paper will discuss classical and recent
      epidemiologic, pathophysiologic, and clinical aspects of CAD in CKD patients. 

PMID- 24734179
TI  - Gray and green revisited: a multidisciplinary perspective of gardens, gardening,
      and the aging process.
AB  - Over fourteen years ago, the concept of "gray and green" was first introduced by
      Wright and Lund (2000) to represent a new awareness and a call for increased
      scholarship at the intersection of environmental issues and the aging process.
      This review paper revisits that concept with a fresh perspective on the specific
      role of gardens and gardening in the aging experience. As example, gardening is
      one of the most popular home-based leisure activities in the US and represents an
      important activity in the lives of older adults in a variety of residential
      settings. Yet, there has been a lack of any comprehensive and multidisciplinary
      (science and humanities) examination of the nexus between gardening and the aging
      experience, and in particular with research connections to stewardship and
      caring. In this paper, we review contemporary articles demonstrating the
      multidisciplinarity of gardening and the aging process. First, we will focus on
      the beneficial psychological effects resulting from the cultivation of caring,
      including personal contentment and artistic expression. Second, we will focus on
      stewardship and how gardening increases health, community awareness, and a
      connection to future generations. On the surface, this may demonstrate a
      separation between the humanities and science, but we will clarify a symbiotic
      relationship between the two disciplines in our conclusion. 

PMID- 24734177
TI  - Potential Role of Selenoenzymes and Antioxidant Metabolism in relation to Autism
      Etiology and Pathology.
AB  - Autism and autism spectrum disorders (ASDs) are behaviorally defined, but the
      biochemical pathogenesis of the underlying disease process remains
      uncharacterized. Studies indicate that antioxidant status is diminished in
      autistic subjects, suggesting its pathology is associated with augmented
      production of oxidative species and/or compromised antioxidant metabolism. This
      suggests ASD may result from defects in the metabolism of cellular antioxidants
      which maintain intracellular redox status by quenching reactive oxygen species
      (ROS). Selenium-dependent enzymes (selenoenzymes) are important in maintaining
      intercellular reducing conditions, particularly in the brain. Selenoenzymes are a
      family of ~25 genetically unique proteins, several of which have roles in
      preventing and reversing oxidative damage in brain and endocrine tissues. Since
      the brain's high rate of oxygen consumption is accompanied by high ROS
      production, selenoenzyme activities are particularly important in this tissue.
      Because selenoenzymes can be irreversibly inhibited by many electrophiles,
      exposure to these organic and inorganic agents can diminish selenoenzyme
      dependent antioxidant functions. This can impair brain development, particularly
      via the adverse influence of oxidative stress on epigenetic regulation. Here we
      review the physiological roles of selenoproteins in relation to potential
      biochemical mechanisms of ASD etiology and pathology. 

PMID- 24734180
TI  - Effect of Posture Training with Weighted Kypho-Orthosis (WKO) on Improving
      Balance in Women with Osteoporosis.
AB  - Objectives. To determine the effect of weighted kypho-orthosis (WKO) on improving
      balance in women with osteoporosis. In this nonrandomized controlled clinical
      trial, 31 patients with osteoporosis were included. The patients were assigned to
      two groups: (1) control group who received 4-week home-based daily exercise
      program including weight bearing, back strengthening, and balance exercises and
      (2) intervention group (WKO) who performed aforementioned exercises and wore WKO
      for one hour twice a day. Patients were assessed using clinical balance tests
      (timed up and go test, functional reach test, and unilateral balance test) before
      and 4 weeks after start of treatment. Results. Functional reach and timed up and
      go test were improved significantly in both groups compared to baseline. The
      improvement in intervention group was more significant in comparison to control
      group (P < 0.05). Discussion. Posture training with WKO together with exercise
      program improved two clinical balance tests in women with osteoporosis.
      Conclusion. Posture training support (PTS) applied as WKO together with back
      extension exercises can be prescribed as an intervention in elderly women in
      order to reduce the risk of falling. 

PMID- 24734181
TI  - Oxygen cost of walking in persons with multiple sclerosis: disability matters,
      but why?
AB  - Background. The oxygen cost (O2 cost) of walking is elevated in persons with MS,
      particularly as a function of increasing disability status. Objective. The
      current study examined symptomatic (i.e., fatigue, pain, anxiety, and depression)
      and gait (i.e., velocity, cadence, and step length) variables that might explain
      why disability status is associated with O2 cost of walking in persons with MS.
      Materials and Methods. 82 participants completed the Patient-Determined Disease
      Steps, Fatigue Severity Scale, McGill Pain Questionnaire, and Hospital Anxiety
      and Depression Scale and undertook 2 trials of walking on a GAITRite electronic
      walkway. Participants then completed a six-minute walk test with concurrent
      assessment of expired gases for quantifying oxygen consumption and O2 cost of
      walking. Results. Disability (r = 0.55) as well as fatigue (r = 0.22), gait
      velocity (r = -0.62), cadence (r = -0.73), and step length (r = -0.53) were
      associated with the O2 cost of walking. Cadence (beta = -0.67), but not step
      length (beta = -0.14) or fatigue (beta = -0.10), explained the association
      between disability and the O2 cost of walking. Conclusions. These results
      highlight cadence as a target of rehabilitation for increasing metabolic
      efficiency during walking among those with MS, particularly as a function of
      worsening disability. 

PMID- 24734182
TI  - Fatigue is associated with poor sleep in people with multiple sclerosis and
      cognitive impairment.
AB  - Background. Fatigue is the most common symptom in people with multiple sclerosis
      (MS). Poor sleep also occurs in this population. Objective. The objective of this
      study was to determine the relationship between fatigue and sleep quality in
      people with MS and cognitive impairment. Method. This cross-sectional study
      assessed relationships among fatigue, assessed with the Modified Fatigue Impact
      Scale (MFIS) and the Fatigue Severity Scale (FSS), sleep quality assessed with
      the Pittsburg Sleep Quality Index (PSQI), and demographics in 121 people with MS
      and cognitive impairment. Results. Fatigue was significantly correlated with poor
      sleep quality (MFIS: F = 15.60, P < 0.01; FSS: F = 12.09, P < 0.01). FSS scores
      were also significantly correlated with the PSQI subscore for daytime dysfunction
      and MFIS scores were significantly correlated with disability, age, and the PSQI
      subscores for sleep quality, sleep duration, and daytime dysfunction.
      Conclusions. This study demonstrates a relationship between fatigue and sleep
      quality in individuals with MS and cognitive impairment. 

PMID- 24734183
TI  - Significance of maternal and cord blood nucleated red blood cell count in
      pregnancies complicated by preeclampsia.
AB  - OBJECTIVES: To evaluate the effect of preeclampsia on the cord blood and maternal
      NRBC count and to correlate NRBC count and neonatal outcome in preeclampsia and
      control groups. STUDY DESIGN: This is a prospective case control observational
      study. PATIENTS AND METHODS: Maternal and cord blood NRBC counts were studied in
      50 preeclamptic women and 50 healthy pregnant women. Using automated cell counter
      total leucocyte count was obtained and peripheral smear was prepared to obtain
      NRBC count. Corrected WBC count and NRBC count/100 leucocytes in maternal venous
      blood and in cord blood were compared between the 2 groups. RESULTS: No
      significant differences were found in corrected WBC count in maternal and cord
      blood in cases and controls. Significant differences were found in mean cord
      blood NRBC count in preeclampsia and control groups (40.0 +/- 85.1 and 5.9 +/-
      6.3, P = 0.006). The mean maternal NRBC count in two groups was 2.4 +/- 9.0 and
      0.8 +/- 1.5, respectively (P = 0.214). Cord blood NRBC count cut off value <= 13
      could rule out adverse neonatal outcome with a sensitivity of 63% and specificity
      of 89%. CONCLUSION: Cord blood NRBC are significantly raised in preeclampsia.
      Neonates with elevated cord blood NRBC counts are more likely to have IUGR, low
      birth weight, neonatal ICU admission, respiratory distress syndrome, and assisted
      ventilation. Below the count of 13/100 leucocytes, adverse neonatal outcome is
      quite less likely.

PMID- 24734184
TI  - Safety and efficacy of misoprostol versus oxytocin for the prevention of
      postpartum hemorrhage.
AB  - Postpartum hemorrhage (PPH) is the commonest cause of maternal death worldwide.
      Studies suggest that the use of misoprostol may be beneficial in clinical
      settings where oxytocin is unavailable. The aim of this study was to compare the
      safety and efficacy of oxytocin and misoprostol when used in the prevention of
      PPH. In a double-blind randomized controlled trial, 400 pregnant women who had a
      vaginal delivery were assigned into two groups: to receive either 20 IU of
      oxytocin in 1000 mL Ringer's solution and two placebo tablets or 400 mcg oral
      misoprostol (as two tablets) and 2 mL normal saline in 1000 mL Ringer's solution.
      The quantity of blood loss was higher in the oxytocin group in comparison to the
      misoprostol group. There was no significant difference in the decrease in
      hematocrit and hemoglobin between the two groups. Although there was no
      significant difference in the need for transfusions between the two groups, the
      patients in the oxytocin group had greater need for additional oxytocin. Results
      from this study indicate that it may be considered as an alternative for oxytocin
      in low resource clinical settings. This study is registered with
      ClinicalTrials.gov NCT01863706.

PMID- 24734185
TI  - A bioclinical pattern for the early diagnosis of cardioembolic stroke.
AB  - Background and Scope. Early etiologic diagnosis of ischemic stroke subtype guides
      acute management and treatment. We aim to evaluate if plasma biomarkers can
      predict stroke subtypes in the early phase from stroke onset. Methods. Plasma N
      terminal prohormone of brain natriuretic peptide (NT-proBNP), D-dimer, C-reactive
      protein, serum albumin, and globulin levels have been investigated in 114
      consecutive patients presenting at the emergency room within 6 hours of the
      ischemic stroke onset. Plasma levels of biomarkers have been correlated with
      stroke aetiology (based on TOAST criteria) by multivariable logistic regression
      analysis, adjusted for several covariates. Results. Of the 114 patients, 34 (30%)
      had cardioembolic stroke, 27 (23%) atherothrombotic stroke, 19 (17%) lacunar
      stroke, and 34 (30%) stroke of undetermined origin. Patients with cardioembolic
      stroke had significantly higher levels of NT-proBNP and lower globulin/albumin
      (G/A) ratio compared with the other subgroups. At multiple logistic regression NT
      proBNP > 200 pg/mL, G/A ratio > 0.70, and NIHSS score were independent predictors
      of cardioembolic stroke with high accuracy of the model, either including (AUC,
      0.91) or excluding (AUC, 0.84) atrial fibrillation. Conclusions. A prediction
      model that includes NT-proBNP, G/A ratio, and NIHSS score can be useful for the
      early etiologic diagnosis of ischemic stroke. 

PMID- 24734186
TI  - Correlation between PFGE Groups and mrp/epf/sly Genotypes of Human Streptococcus
      suis Serotype 2 in Northern Thailand.
AB  - Streptococcus suis infection is a severe zoonotic disease commonly found in
      Northern Thailand where people often consume raw pork and/or pig's blood. The
      most frequent clinical presentations are meningitis, sepsis, and endocarditis
      with higher rate of mortality and hearing loss sequelae. To clarify the
      correlation between pulsed-field gel electrophoresis (PFGE) groups and
      mrp/epf/sly genotypes of S. suis serotype 2, 62 patient and 4 healthy pig
      isolates from Northern Thailand were studied. By PFGE analysis, at 66% homology,
      most human isolates (69.4%) and 1 pig isolate were in group A, whereas 14.5% of
      human isolates and 3 out of 4 pig isolates were in group D. According to
      mrp/epf/sly genotypes, 80.6% of human isolates were identified in mrp (+) epf (-)
      sly (-) and only 12.9% were in mrp (-) epf (-) sly (+) genotypes; in contrast, 1
      and 3 pig isolates were detected in these two genotypes, respectively.
      Interestingly, all isolates of S. suis serotype 2 classified in PFGE groups A, B,
      and E were set in mrp (+) epf (-) sly (-) genotypes. These data show a close
      correlation between PFGE groups and mrp/epf/sly genotypes of human S. suis
      serotype 2. 

PMID- 24734187
TI  - One-Year Period Prevalence of Oral Aphthous Ulcers and Oral Health-Related
      Quality of Life in Patients with Behcet's Disease.
AB  - The aim of this study was to investigate the 1-year period prevalence of oral
      aphthous ulcers (OAUs) and their association with oral health-related quality of
      life (OHQOL) in patients with Behcet's disease (BD) and in the general
      population. In this cross-sectional study, 675 patients with Behcet's disease (BD
      group) and 1,097 males and females in the Japanese general population (control
      group) completed both questionnaires on their OAU status during the prior year
      and the General Oral Health Assessment Index (GOHAI). In the BD group, 84% of
      patients reported experiencing an OAU during the previous year, and the mean
      number of OAUs/year was 13. In the control group, 31% of individuals experienced
      an OAU during the previous year, and the mean number of OAUs/year was one.
      Multivariate analysis indicated that both BD patients (OR, 6.2; 95% CI, 4.8-8.0)
      and controls (OR, 2.6; 95% CI, 2.0-3.5) who had OAUs at least twice per year were
      more likely to have GOHAI scores below the norm than were controls who had fewer
      than two OAUs per year. The association between HLA-B*51 and OAUs remains
      unknown. The presence of OAUs has a negative effect on the OHQOL of patients with
      BD. 

PMID- 24734188
TI  - A comprehensive prospective clinical study of hydatid disease.
AB  - The actual prevalence of hydatid disease in northern part of India is found more
      than usually interpreted. The present study has been done on 25 patients
      suffering from hydatid disease of various sites and treated during June 2009 to
      November 2011 at JLN Medical College and Hospital, Ajmer, with the aim of
      studying the clinical manifestations of hydatid disease of different sites and/or
      organ system and of analysing the morbidity and mortality of hydatid disease. The
      age, sex, h/o dog contact, duration of hospital stay, clinical presentation,
      treatment advised, findings and difficulties encountered during operation, and
      postoperative management of patients as well as morbidity and mortality were
      recorded and analysed. We observed that the mean age was 40 years. The sex
      incidence revealed female preponderance in the study (M : F: 1 : 2). Duration of
      illness in the present study varied from 1 month to 6 years in case of liver
      hydatid disease. Majority of patients were from rural areas (21) and the
      remaining (4) from urban areas. Swelling was the most common presenting feature.
      Incidence of hydatid disease at unusual sites in India is higher than in other
      parts of the world. 

PMID- 24734190
TI  - Prevalence of psychological disorders in patients with alopecia areata in
      comparison with normal subjects.
AB  - Alopecia areata is a chronic disease with a great impact on the patient's quality
      of life. In this study we reviewed the frequency of psychological disorders in
      patients with alopecia areata in comparison to a control group. We enrolled 40
      patients with alopecia areata and a 40-volunteer random age-sex matched control
      group. The study is based on anxiety and Beck Depression Inventory (BDI) and the
      Eysenck Personality Questionnaire (EPQ). Analytical evaluation was done by Mann
      Whitney, Kruskal Wallis, and t-tests. There was a significant difference between
      the case and control group regarding the prevalence of depression (P value =
      0.008), anxiety (P value = 0.003), and neuroticism (P value = 0.05). There was no
      significant differences regarding extraversion (P value = 0.249), psychosis (P
      value = 0.147), and lying (P value = 0.899) between the two groups. In alopecia
      areata involving the head, there was a significant relation only between
      neuroticism (P value = 0.045) and lying (P value = 0.005). The facial involvement
      had a significant relation with depression (P value = 0.020), anxiety (P value =
      0.019), and neuroticism (P value = 0.029). The frequency of psychological
      disorders in the case group is significantly greater than the control group. 

PMID- 24734189
TI  - Comparison of Laboratory Data of Acute Cholangitis Patients Treated with or
      without Immunosuppressive Drugs.
AB  - Objective. Symptoms and laboratory data between acute cholangitis (AC) patients
      treated with and AC patients treated without immunosuppressive drugs
      (corticosteroids or methotrexate) were compared to identify factors that can be
      meaningful to the diagnosis of AC. Methods. The Wilcoxon signed-rank test was
      used for comparison of baseline variables between the patients with AC treated
      with immunosuppressive drugs and those without it. The chi-squared test was used
      in the analysis of the symptoms. Results. In total, 69 patients with AC were
      enrolled. Fifteen patients were treated with immunosuppressants due to rheumatoid
      arthritis or other collagen diseases. Jaundice was less frequent in the patients
      treated with immunosuppressive drugs (P = 0.0351). T-Bil level was marginally
      lower in the patients treated with immunosuppressants (P = 0.086). AST and ALT
      levels were lower in the patients treated with immunosuppressants (P = 0.0417 and
      0.022, respectively). Conclusions. The frequency of jaundice and AST and ALT
      levels were lower in the patients treated with immunosuppressive drugs. It is
      recommended that care be taken to evaluate jaundice, AST level, and ALT level in
      the diagnosis of AC. 

PMID- 24734191
TI  - Incidence of retinopathy of prematurity in extremely premature infants.
AB  - Purpose. To investigate the incidence and the severity of retinopathy of
      prematurity (ROP) in extremely preterm infants born before 28 weeks of gestation
      in southeastern Turkey. Methods. A retrospective chart review was performed for
      infants born before 28 weeks of gestation. The following data were reviewed:
      gender, gestational age (GA), birth weight (BW), zone and stage of ROP, presence
      of plus disease, and treatment for ROP if needed. Infants were divided into 2
      groups according to GA as follows: group 1 included infants of GAs 25 weeks and
      under; group 2 included infants of GAs less than 28 weeks and over 25 weeks.
      Results. The incidence of any ROP in the whole cohort, in group 1, and in group
      2, was 66.0%, 95.5%, and 58.6%, respectively. Incidence of any ROP was
      significantly associated with BW and GA (P = 0.014 and P = 0.002, resp.). The
      overall incidence of type 1 ROP was 35.8% (59.1% in group 1 and 29.9% in group
      2). Development of type 1 ROP was independently associated with GA. Conclusion.
      Any ROP was significantly associated with BW and GA. Extremely premature infants
      with lower GA were found to be more likely to develop type 1 ROP. BW cannot
      predict the development of type 1 ROP. 

PMID- 24734192
TI  - Antihyperlipidemic and Antioxidant Potential of Paeonia emodi Royle against High
      Fat Diet Induced Oxidative Stress.
AB  - The present study was intended to evaluate the effects of Paeonia emodi rhizome
      extracts on serum triglycerides (TGs), total cholesterol (TC), low density
      lipoprotein cholesterol (LDL-c), high density lipoprotein cholesterol (HDL-c),
      atherogenic index (AI), superoxide dismutase (SOD), and glutathione peroxidase
      (GPx). The plant was extensively examined for its in vitro antioxidant activity,
      and the preliminary phytochemical screening was carried out using standard
      protocols. Male Wistar rats were induced with hyperlipidemia using high-fat diet
      and were treated orally with hydroalcoholic and aqueous extracts at the dose of
      200 mg/kg bw for 30 days. TGs, TC, LDL-c, and AI were significantly reduced while
      HDL-c, SOD, and GPx levels rose to a considerable extent. After subjecting to
      acute toxicity testing, the extracts were found to be safe. The observations
      suggest antihyperlipidemic and antioxidant potential of P. emodi in high-fat diet
      induced hyperlipidemic/oxidative stressed rats. 

PMID- 24734193
TI  - Promotive effect of topical ketoconazole, minoxidil, and minoxidil with tretinoin
      on hair growth in male mice.
AB  - Recently topical use of 2% Ketoconazole solution has been reported to have a
      therapeutic effect on androgenic alopecia. Minoxidil is a vasodilatory medication
      used primarily as antihypertensive drug. It was discovered to have the side
      effect of hair growth and reversing baldness. Tretinoin is commonly used
      topically for acne treatment and in the treatment of photoaging. It is used by
      some as hair loss treatment. Objective. To compare the stimulatory effect of
      Ketoconazole, Minoxidil, and Minoxidil with Tretinoin on hair growth in a mouse
      model. Materials and Methods. Coat hairs on the dorsal skin of seven weeks old
      male mice were gently clipped and then stained by using commercial dye. These
      mice were divided into four groups each of five treated with topical application
      of ethanol 95%, Ketoconazole solution 2%, Minoxidil solution 5%, and Minoxidil
      with Tretinoin solution 0.1%, respectively. The drugs were applied once daily for
      three weeks, the clipped area was photographed, and the ratio of regrown coat
      area was calculated. Results. The results demonstrated that Ketoconazole,
      Minoxidil, and Minoxidil with Tretinoin had a significant stimulatory effect on
      hair growth compared with the control group and Minoxidil was the most effective
      drug among them. 

PMID- 24734194
TI  - Modulation of arachidonic Acid metabolism in the rat kidney by sulforaphane:
      implications for regulation of blood pressure.
AB  - Background. We investigated the effects of sulforaphane (SF), the main active
      isothiocyanate in cruciferous vegetables, on arachidonic acid (AA) metabolism in
      the kidney and its effect on arterial blood pressure, using spontaneously
      hypertensive rats (SHR) as models. Methods. Rats were treated for 8 weeks with
      either drinking water alone (control) or SF (20 or 40 mg/kg) added to drinking
      water. Mean arterial pressure (MAP) was measured at 7-day intervals throughout
      the study. At the end of treatment rats were euthanized, and kidneys were
      harvested to prepare microsomes and measure enzymes involved in regulation of
      vasoactive metabolites: CYP4A, the key enzyme in the formation of 20
      hydroxyeicosatetraenoic acid, and the soluble epoxide hydrolase, which is
      responsible for the degradation of the vasodilator metabolites such as
      epoxyeicosatetraenoic acids. Effect of SF on kidney expression of CYP4A was
      investigated by immunoblotting. Results. We found that treatment with SF leads to
      significant reductions in both, the expression and activity of renal CYP4A
      isozymes, as well as the activity of soluble epoxide hydrolase (sEH). Consistent
      with these data, we have found that treatment with SF resisted the progressive
      rise in MAP in the developing SHR in a dose-dependent manner. Conclusion. This is
      the first demonstration that SF modulates the metabolism of AA by both P450
      enzymes and sEH in SHR rats. This may represent a novel mechanism by which SF
      protects SHR rats against the progressive rise in blood pressure. 

PMID- 24734195
TI  - Can HLA-DRB4 Help to Identify Asthmatic Patients at Risk of Churg-Strauss
      Syndrome?
AB  - HLA-DRB4 gene is associated with Churg-Strauss syndrome (CSS), a systemic
      eosinophilic vasculitis with a prodromal phase characterized by severe asthma,
      eosinophilia, nasal polyposis, and sinusitis. Aim of this study was to evaluate
      if the presence of HLA-DRB4 in asthmatic patients is associated with a clinical
      picture resembling that of the prodromal phase of CSS. HLA-DRB1 was determined in
      a cohort of 159 asthmatic patients and its frequency was compared with that of
      1808 blood donors. HLA-DRB4 presence/absence was correlated with clinical
      features, including sinusitis, nasal polyposis, eosinophils, antiasthmatic drugs,
      asthma severity, and pulmonary function tests. HLA-DRB4 gene was associated with
      severe persistent asthma before treatment (P < 0.02), near fatal or severe
      hypoxemic asthma (P < 0.01), sinusitis (P < 0.01), nasal polyposis (P < 0.01),
      number of patients with eosinophils >1000/ MU l: (P < 0.05), need of
      beclomethasone >1000-2000  MU g/daily (P < 0.001), use of a third controller (P <
      0.05), and oral prednisone (P < 0.02). HLA-DRB4 gene is associated in asthmatic
      patients with a clinical picture characterized by asthma severity, sinusitis,
      nasal polyposis, and eosinophilia closely resembling that of the prodromal phase
      of CSS and might be useful to suspect corticosteroids-masked cases of CSS. 

PMID- 24734196
TI  - Job Burnout, Mood State, and Cardiovascular Variable Changes of Doctors and
      Nurses in a Children's Hospital in China.
AB  - Aims. This study examines mood and cardiovascular variables related to job stress
      and burnout in hospital personnel. Main Methods. 400 nurses and physicians from a
      children's hospital in China were recruited. Participants completed job stress,
      burnout, and mood state questionnaires. Cardiovascular variables such as body
      mass index (BMI), triglyceride (TG), and high density lipoprotein (HDL) were
      measured. Key Findings. Job stress and burnout were significantly associated with
      mood state. Statistically significant correlations were found between
      triglyceride levels and job stress scores (r = 0.175, P < 0.01), BMI and job
      stress scores (r = 0.121, P < 0.05), and HDL levels and job stress scores (r = 
      0.117, P < 0.05). Significance. Mood state changes may be related to job stress
      and job burnout, in turn, associated with triglycerides and HDL levels. Public
      health implications and interventions are discussed. 

PMID- 24734197
TI  - Effects of ocular dominance on contrast sensitivity in middle-aged people.
AB  - Purpose. Our aim was to compare contrast sensitivity values of the dominant and
      nondominant eyes of healthy middle-aged subjects. Material and Methods. Ninety
      eyes of 45 healthy middle-aged subjects (30 males and 15 females) were included
      in this study. Patients were aged between 40 and 60 years, having uncorrected
      visual acuity (UCVA) of 20/25 or better (Snellen chart). Ocular dominance was
      determined by hole-in-the-card test. Functional acuity contrast testing
      (F.A.C.T.) was measured using the Optec 6500 vision testing system (Stereo
      Optical Co. Inc., Chicago, IL, USA) under both photopic and mesopic conditions.
      Results. At all spatial frequencies (1.5, 3, 6, 12, and 18 cpd), under mesopic
      conditions, the contrast sensitivity values of the dominant eyes were slightly
      greater than those of the nondominant eyes; but only 18 cpd spatial frequency
      measurements' difference was statistically significant (P = 0.035). Under
      photopic conditions, the contrast sensitivity values of the dominant eyes and non
      dominant eyes were similar at all spatial frequencies (P > 0.05). Conclusions.
      The photopic and mesopic contrast sensitivity values of dominant and nondominant
      eyes of healthy middle-aged people were similar at all spatial frequencies,
      except at mesopic 18 cpd spatial frequency. 

PMID- 24734198
TI  - Outcomes and control rates for I-125 plaque brachytherapy for uveal melanoma: a
      community-based institutional experience.
AB  - Purpose. To evaluate our community-based institutional experience with plaque
      brachytherapy for uveal melanomas with a focus on local control rates, factors
      impacting disease progression, and dosimetric parameters impacting treatment
      toxicity. Methods and Materials. Our institution was retrospectively reviewed
      from 1996 to 2011; all patients who underwent plaque brachytherapy for uveal
      melanoma were included. Follow-up data were collected regarding local control,
      distant metastases, and side effects from treatment. Analysis was performed on
      factors impacting treatment outcomes and treatment toxicity. Results. A total of
      107 patients underwent plaque brachytherapy, of which 88 had follow-up data
      available. Local control at 10 years was 94%. Freedom from progression (FFP) and
      overall survival at 10 years were 83% and 79%, respectively. On univariate
      analysis, there were no tumor or dosimetric treatment characteristics that were
      found to have a prognostic impact on FFP. Brachytherapy treatment was well
      tolerated, with clinically useful vision (>20/200) maintained in 64% of patients.
      Statistically significant dosimetric relationships were established with
      cataract, glaucoma, and retinopathy development (greatest P = 0.05). Conclusions.
      Treatment with plaque brachytherapy demonstrates excellent outcomes in a
      community-based setting. It is well tolerated and should remain a standard of
      care for COMS medium sized tumors. 

PMID- 24734199
TI  - Feasibility of endoscopic treatment of middle ear myoclonus: a cadaveric study.
AB  - Stapedius and tensor tympani tenotomy is a relatively simple surgical procedure
      commonly performed to control pulsatile tinnitus due to middle ear myoclonus and
      for several other indications. We designed a cadaveric study to assess the
      feasibility of an entirely endoscopic approach to stapedius and tensor tympani
      tenotomy. We performed this endoscopic ear surgery in 10 cadaveric temporal bones
      and summarized our experience. Endoscopic stapedius and tensor tympani section is
      a new, minimally invasive treatment option for middle ear myoclonus that should
      be considered as the first line surgical approach in patients who fail medical
      therapy. The use of an endoscopic approach allows for easier access and vastly
      superior visualization of the relevant anatomy, which in turn allows the surgeon
      to minimize tissue dissection. The entire operation, including raising the
      tympanomeatal flap and tendon section, can be safely completed under
      visualization with a rigid endoscope. 

PMID- 24734200
TI  - Oral tongue squamous cell carcinoma in young women: a matched comparison-do
      outcomes justify treatment intensity?
AB  - Background. The incidence of oral tongue squamous cell carcinoma (OTSCC) in young
      women is increasing with uncertain outcomes compared to traditional patients.
      Published outcomes data are at odds in this cohort of young women. Methods.
      Retrospective analysis comparing demographic, clinicopathologic, and outcomes
      data of women OTSCC patients younger than 45 years old matched 1 : 2 by stage
      with men both younger and older than 45 and women older than 45. Results. No
      disease-free or overall survival differences were found between cohorts. Young
      women were significantly more likely to receive radiation therapy, particularly
      in stage I disease, even when controlling for common pathologic indications.
      Conclusions. OTSCC in young women was not associated with worse outcomes compared
      to a matched cohort of other patients. Increased frequency of radiation treatment
      for this cohort may not be justified. 

PMID- 24734201
TI  - Novel closing method using subcutaneous continuous drain for preventing surgical
      site infections in radical cystectomy.
AB  - To reduce the incidence of surgical site infection (SSI) after radical
      cystectomy, a new closing method using subcutaneous continuous aspiration drain
      was developed and compared to the conventional closing method. The new method
      involved (a) closed aspiration with an indwelling aspiration drain without suture
      of the subcutaneous fat and (b) covering with hydrocolloid wound dressing after
      suture of the dermis with 4-0 absorbable thread and reinforcement using strips.
      The incidence of SSI was significantly improved by using the new method.
      Furthermore, univariate and multivariate analysis associated with SSI revealed
      that the new closing method was statistically correlated with 85% reduction of
      SSI (odds ratio: 0.15, 95% confidence interval: 0.03-0.69).Our new method using
      continuous aspiration with subcutaneous drain is useful for preventing SSI
      through removal of effusions and reduction of dead space by apposition of the
      subcutaneous fat. 

PMID- 24734202
TI  - Retrograde robotic radical prostatectomy: description of a new technique and
      early perioperative outcomes.
AB  - Objectives. This research was conducted to describe a novel technique for
      performing robotic-assisted laparoscopic prostatectomy (RALP) using a retrograde
      approach that mimics the classic open surgical technique. Methods. From June 2009
      to March 2011, we performed 18 nonconsecutive RALPs using a novel retrograde
      approach. Patients were initially selected with D'Amico low to intermediate risk
      disease. Pre-, intra-, and postoperative data were analyzed in all patients.
      Results. All 18 patients had successful surgery without any intraoperative
      complications. Mean preoperative PSA was 6.0 ng/mL. Nine patients had biopsy
      Gleason score (GS) 6, seven patients had GS 7, and two patients had GS 8.
      Fourteen patients had clinical stage T1c and four patients had stage T2a. Mean
      operative time was 198 minutes, with a mean robotic console time of 168 minutes.
      Fifteen patients had T2 disease on the final pathology and three had T3 disease.
      With a median follow-up of 11 months, 10 patients had an undetectable PSA.
      Conclusions. Our early experience with retrograde robotic-assisted laparoscopic
      prostatectomy demonstrates the feasibility of this approach with early outcomes
      comparable to the contemporary antegrade approach. Long-term study with a greater
      number of patients will be necessary to fully evaluate the oncologic and
      functional outcomes using this technique. 

PMID- 24734203
TI  - Active calcium/calmodulin-dependent protein kinase II (CaMKII) regulates NMDA
      receptor mediated postischemic long-term potentiation (i-LTP) by promoting the
      interaction between CaMKII and NMDA receptors in ischemia.
AB  - Active calcium/calmodulin-dependent protein kinase II (CaMKII) has been reported
      to take a critical role in the induction of long-term potentiation (LTP). Changes
      in CaMKII activity were detected in various ischemia models. It is tempting to
      know whether and how CaMKII takes a role in NMDA receptor (NMDAR)-mediated
      postischemic long-term potentiation (NMDA i-LTP). Here, we monitored changes in
      NMDAR-mediated field excitatory postsynaptic potentials (NMDA fEPSPs) at
      different time points following ischemia onset in vitro oxygen and glucose
      deprivation (OGD) ischemia model. We found that 10 min OGD treatment induced
      significant i-LTP in NMDA fEPSPs, whereas shorter (3 min) or longer (25 min) OGD
      treatment failed to induce prominent NMDA i-LTP. CaMKII activity or CaMKII
      autophosphorylation displays a similar bifurcated trend at different time points
      following onset of ischemia both in vitro OGD or in vivo photothrombotic lesion
      (PT) models, suggesting a correlation of increased CaMKII activity or CaMKII
      autophosphorylation with NMDA i-LTP. Disturbing the association between CaMKII
      and GluN2B subunit of NMDARs with short cell-permeable peptides Tat-GluN2B
      reversed NMDA i-LTP induced by OGD treatment. The results provide support to a
      notion that increased interaction between NMDAR and CaMKII following ischemia
      induced increased CaMKII activity and autophosphorylation is essential for
      induction of NMDA i-LTP. 

PMID- 24734204
TI  - Prevalence, clinical features, and outcome of pseudomonas bacteremia in under
      five diarrheal children in bangladesh.
AB  - We sought to evaluate the prevalence, associated factors, and outcome of under
      five diarrheal children with either sex having Pseudomonas bacteremia. A
      retrospective chart review of under-five diarrheal children admitted to the Dhaka
      Hospital of the International Centre for Diarrhoeal Disease Research, Bangladesh
      (icddr,b), from January 2011 to December 2011 was performed using an online
      hospital management system. Children with Pseudomonas bacteremia constituted the
      cases (n = 31), and the controls (n = 124), without Pseudomonas bacteremia, were
      randomly selected. The prevalence of Pseudomonas bacteremia was 1% (31/5,179).
      The Pseudomonas was multidrug resistant but was 84% sensitive to ceftazidime and
      100% to imipenem. The case-fatality rate was significantly higher among the cases
      than the controls (26% versus 5%; P = 0.003). In logistic regression analysis,
      after adjusting for potential confounders such as severe wasting, severe
      underweight, severe pneumonia, and young age (11.71 (4.0, 18.0) months), the
      cases more often presented with absent peripheral pulses in absence of
      dehydration (95% CI = 2.31-24.45) on admission. This finding underscores the
      importance of early identification of this simple clinical sign to ensure prompt
      management including fluid resuscitation and broad spectrum antibiotics to help
      reduce morbidity and mortality in such children, especially in resource-poor
      settings. 

PMID- 24734205
TI  - Comparative Assessment of Factors Involved in Acetoin Synthesis by Bacillus
      subtilis 168.
AB  - Acetoin is widely used as flavor agent and serves as a precursor for chemical
      synthesis. Here we focused on identifying the best physiological conditions
      (initial substrate concentrations, pH, temperature, and agitation) for enhanced
      acetoin accumulation by Bacillus subtilis 168. The optimal physiological
      conditions support maximum acetoin accumulation by minimizing byproduct (acetate
      and butanediol) synthesis and a maximum of 75% enhancement in acetoin yield could
      be achieved. Additionally, the effect of change in ALS (acetolactate synthase)
      and ALDC (acetolactate decarboxylase) activities was evaluated on acetoin
      accumulation. Increasing ALS and ALDC enzyme activities led to efficient
      utilization of pyruvate towards acetoin accumulation and about 80% enhancement in
      acetoin accumulation was observed. 

PMID- 24734206
TI  - The psychogeriatric patient in the emergency room: focus on management and
      disposition.
AB  - Background. The growing geriatric population in the United States (US) has
      prompted better understanding of treatment of the elderly in the hospital and
      emergency room (ER) settings. This study examines factors influencing the
      disposition of psychogeriatric patients after their initial presentation in the
      ER. Methods. Data was collected on patients 65 years of age or older arriving at
      the ER of a large urban hospital in the USA (January 2009-December 2010).
      Results. Of the total subjects (n = 95) included in the study, majority were
      females (66.3%) with an average age of 75.5 years. The chief complaint for
      psychogeriatric patients coming to the ER was delirium (61.6%). Caucasians were
      significantly more likely than African-American patients to get a psychiatric
      consult (33% versus 9%). Patients with delirium were less likely than patients
      with other psychiatric complaints to get a psychiatric consult in the ER (1.2%
      versus 47.2%) and less likely to be referred to a psychiatric inpatient unit
      compared to patients with other psychiatric complaints (2.4% versus 16.7%).
      Conclusion. Even though delirium is the most common reason for ER visits among
      psychogeriatric patients, very few delirium patients got a psychiatric
      consultation in the ER. A well-equipped geriatric psychiatry unit can manage
      delirium and associated causes. 

PMID- 24734207
TI  - Osteoporosis health beliefs of women with increased risk of the female athlete
      triad.
AB  - Women with increased risk of the female athlete triad (Triad) are more
      susceptible to osteoporosis compared to other women. The study included 65 women
      with increased risk of the Triad who had their osteoporosis health beliefs
      measured to assess their concern for the disease. Participants were female
      collegiate cross-country runners at different levels of competition, including
      National Association of Intercollegiate Athletics (NAIA) and National Collegiate
      Athletic Association (NCAA) Divisions III, II, and I. Although these participants
      have an increased risk of the Triad and are more susceptible to osteoporosis, on
      a scale of 1 to 5, results showed that they had low to moderate perceived
      susceptibility to osteoporosis with a mean score as high as 2.81 and moderate
      perceived severity of osteoporosis with a mean score as high as 3.38. A
      statistically significant difference in perceived susceptibility to osteoporosis
      was found between female collegiate cross-country runners in the NAIA and those
      in the NCAA DIII. Reasons that could explain relatively low levels of concern for
      osteoporosis in female collegiate cross-country runners and reasons for
      significant differences in perceived susceptibility to osteoporosis are given,
      and recommendations for health education and intervention to help care for this
      population are provided. 

PMID- 24734208
TI  - Study assessing the quality of quantification of estrogen receptor protein
      expression by immunohistochemistry and gene expression in breast cancer.
AB  - Although immunohistochemistry (IHC) is a widely used technique to classify tumors
      in ER-positive versus ER-negative ones, interlab variabilities can occur. This
      study aims to investigate the influences of preanalytical and analytical factors
      on IHC results. For this purpose, the different steps of the preparation of IHC
      sections and scoring procedures were compared between two participating
      laboratories and a central lab. There was a significant positive correlation
      between the IHC results of the participating laboratories and those of the
      central lab (correlation coefficient > 0.600; P<0.05). Nevertheless, some
      discordant cases for immunostaining (5.3% for ER and 5.6% for PR) and for scoring
      (10.5% for PR) occur at site 1. Comparing IHC results with ESR1 gene expression
      results revealed a significant positive correlation (correlation coefficients >
      0.769; P<0.05). PCR results of ER target genes showed some heterogeneity in the
      ER-signalling pathway. These results suggest that differences in the IHC
      procedure between these laboratories did not have a big influence on the end
      result. Nevertheless, discordant cases caused by preanalytical and analytical lab
      specific procedures have been identified. 

PMID- 24734209
TI  - A new method for the analysis of bacterial endotoxins in ultrapure paraffin oil.
AB  - The paper demonstrates the feasibility of the gel-clot method for the analysis of
      bacterial endotoxins in water extracts of ultrapure paraffin oil which is a water
      insoluble oily medical device. Because ultrapure paraffin oil is water insoluble
      oily liquid, the ultrapure paraffin oil (10 mL) was shaken with 10 mL water for
      15 minutes at 2000 rpm, the endotoxin present was extracted to the aqueous phase
      without interference inhibition/enhancement of the product, the recovery of the
      endotoxin added to the ultrapure paraffin oil was determined. A validation study
      confirmed that endotoxins present in ultrapure paraffin oil which is water
      insoluble liquid medical device pass over into the aqueous phase at
      concentrations of 20, 10, and 5 EU/mL with recoveries of 94.2% to 111%. So the
      conclusion is that the gel-clot test is suitable for detecting bacterial
      endotoxins in ultrapure paraffin oil which is a water insoluble oily medical
      device. 

PMID- 24734210
TI  - Concurrent Associations between Physical Activity, Screen Time, and Sleep
      Duration with Childhood Obesity.
AB  - Aim. To examine the simultaneous influence of physical activity, screen time, and
      sleep duration recommendations on the odds of childhood obesity (including
      overweight). Methods. Physical activity was assessed via pedometer and screen
      time, and sleep duration were assessed via survey in a cross sectional sample of
      674 children (aged 7-12 years) from two Midwestern communities in the fall of
      2005. Participants were cross tabulated into four groups depending on how many
      recommendations were being met (0, 1, 2, or all 3). Linear and logistic
      regression were used to examine the influence of physical activity, screen time
      and sleep duration on obesity and interactions among the three variables.
      Results. Children achieving all three recommendations simultaneously (9.2% of
      total sample) were the least likely to be obese. Approximately 16% of boys and 9%
      of girls achieving all recommendations were overweight or obese compared to 53%
      of boys and 42.5% of girls not achieving any. Conclusions. The odds of obesity
      increased in a graded manner for each recommendation which was not met. Meeting
      all three recommendations appears to have a protective effect against obesity.
      Continued efforts are warranted to promote healthy lifestyle behaviors that
      include meeting physical activity, screen time, and sleep duration
      recommendations concurrently. 

PMID- 24734211
TI  - An outbreak of community-associated methicillin-resistant Staphylococcus aureus
      infection in a boarding school in Hong Kong Special Administrative Region
      (China).
AB  - BACKGROUND: In November 2012, an outbreak of community-associated methicillin
      resistant Staphylococcus aureus (CA-MRSA) skin and soft tissue infections
      affecting students at a boarding school in Hong Kong Special Administrative
      Region (China) was detected. METHODS: A case was defined as any student or staff
      notified with MRSA infection from 25 October 2012 to 5 July 2013 with the
      clinical isolate being of staphylococcal cassette chromosome mec type IV or V and
      positive for Panton-Valentine leukocidin gene. We conducted field investigations,
      advised on control measures and enhanced surveillance for skin and soft tissue
      infections at the school. Decolonization therapies were offered to all cases and
      contacts, and carrier screening was conducted. RESULTS: There were five cases;
      two (40%) were hospitalized and three (60%) required surgical treatments. Initial
      screening comprised 240 students and 81 staff members. Overall, four cases (80%)
      plus eight other students (3.3%) were carriers, with eight of 12 (66.7%) from the
      same dormitory. All staff members screened negative. After intensified control
      measures, the number of students screened positive for CA-MRSA decreased from
      nine to one with no more cases identified in the school. CONCLUSION:
      Identification of carriers, decolonization therapy, monitoring of cases and
      contacts and strengthening of environmental and personal hygiene were control
      measures that helped contain this CA-MRSA outbreak in a boarding school in Hong
      Kong Special Administrative Region (China).

PMID- 24734212
TI  - National dengue surveillance in the Lao People's Democratic Republic, 2006-2012:
      epidemiological and laboratory findings.
AB  - Although dengue has been a public health problem for several decades in the Lao
      People's Democratic Republic, the magnitude of the disease burden and
      epidemiological trends remain poorly understood. We analysed national dengue
      surveillance and laboratory data from 2006 to 2012 by person, place and time.
      Between 2006 and 2012, the annual dengue notification rate ranged between 62 and
      367 cases per 100 000 population with an apparent geographical expansion of
      transmission throughout the country in recent years and concurrent co-circulation
      of all four dengue virus subtypes. An electronic database, called Lao People's
      Democratic Republic Early Warning Alert and Response Network, was introduced in
      2008 to provide automated early warning for outbreaks and epidemics. Village
      outbreaks continue to be notified primarily through event-based surveillance,
      whereas the weekly indicator-based system provides systematic assessment of
      annual epidemic cycles. The dengue case data indicate a high and increasing
      burden of disease. Efforts now need to focus on using available data to prompt
      more effective outbreak response and to guide the design and implementation of
      intervention strategies. 

PMID- 24734213
TI  - Natural Anaplasma phagocytophilum infection in ticks from a forest area of
      Selenge province, Mongolia.
AB  - Anaplasma phagocytophilum is a zoonotic agent of public health importance,
      infecting both humans and animals. An investigation of the presence of Anaplasma
      phagocytophilum as well as Anaplasma platys was conducted in a forest area of
      Selenge province, Mongolia, where ticks are widely distributed and tick-borne
      diseases are highly endemic. Ticks were collected and tested using polymerase
      chain reaction based on groEL methodology. Anaplasma phagocytophilum was detected
      in 14 (6%) of Ixodes persulcatus ticks and four (1%) Dermacentor nuttalli ticks;
      infection of Anaplasma platys was detected in 1% of Ixodes persulcatus ticks and
      10% of Dermacentor nuttalli ticks. The phylogenetic tree showed that the
      Anaplasma phagocytophilum clustered with the Russian group, most likely due to
      similar geographical locations. This finding is significant for both veterinary
      and public health officials given that these agents can cause both animal and
      human illness. 

PMID- 24734214
TI  - Epidemiology and control of tuberculosis in the Western Pacific Region: analysis
      of 2012 case notification data.
AB  - Tuberculosis (TB) control in the World Health Organization (WHO) Western Pacific
      Region has seen substantial progress in the last decade, with a 33% reduction in
      prevalent TB cases since 2000. The burden remains immense, however, and national
      TB programmes must evolve and adapt to build upon these gains. Through routine
      surveillance, countries and areas in the Region reported 1.4 million TB cases in
      2012. The case notification rate increased in the early 2000s, appears to have
      stabilized in recent years and is in decline for all forms and new smear-positive
      cases. The age and sex breakdown for smear-positive TB case rates by country
      shows generally higher rates with increased age and declining rates over time for
      all age groups. Treatment success remains high in the Region, with 15 countries
      reaching or maintaining an 85% success rate. HIV testing among TB patients has
      increased gradually along with a slow decline in the number of HIV-positive
      patients found. The trend of TB notification is heavily influenced by
      programmatic improvements in many countries and rapidly changing demographics. It
      appears that cases are being found earlier as reflected in declining rates of
      smear-positive TB and steady rates of TB in all forms. WHO estimates depict a
      decline in TB incidence in the Region. HIV testing, while still low, has
      increased substantially in recent years, with essential TB/HIV services expanding
      in many countries. TB surveillance data, within inherent limitations, is an
      important source of programmatic and epidemiological information. Careful
      interpretation of these findings can provide useful insight for programmatic
      decision-making. 

PMID- 24734215
TI  - Immune checkpoint blockade in malignant mesothelioma: A novel therapeutic
      strategy against a deadly disease?
AB  - Monoclonal antibodies that target immune checkpoints are undoubtedly changing the
      therapeutic landscape of different human malignancies. Here we comment on the
      effects of blocking cytotoxic T lymphocyte-associated protein 4 (CTLA4) by means
      of the monoclonal antibody tremelimumab in patients with refractory malignant
      mesothelioma, a deadly disease with no effective therapeutic options.

PMID- 24734216
TI  - gammadelta T cells for cancer immunotherapy: A systematic review of clinical
      trials.
AB  - gammadelta T cells contribute to the front line of lymphoid antitumor
      surveillance and bridge the gap between innate and adaptive immunity. They can be
      readily expanded to high numbers in vivo and in vitro, starting from the blood of
      cancer patients, and a number of Phase I trials have demonstrated that these
      cells can be employed in cancer immunotherapy. Sufficient patients have received
      gammadelta T cell-based immunotherapies in the context of clinical trials to
      evaluate their utility, and to inform the direction of new trials. A systematic
      approach was used to identify Phase I, Phase II, and feasibility studies testing
      gammadelta T cell-based immunotherapy in cancer patients. Studies were excluded
      from further analysis if they did not provide patient-specific data. Data were
      compiled to evaluate efficacy, with stratification by treatment approach. When
      possible, comparisons were made with the efficacy of second-line conventional
      therapeutic approaches for the same malignancy. Twelve eligible studies were
      identified, providing information on 157 patients who had received gammadelta T
      cell-based immunotherapy. The comparison of objective response data suggests that
      gammadelta T cell-based immunotherapy is superior to current second-line
      therapies for advanced renal cell carcinoma and prostate cancer, but not for non
      small cell lung carcinoma. An evaluation of pooled data from 132 published in
      vitro experiments shows a consistent improvement in the cytotoxicity of
      gammadelta T cells in the presence of antitumor antibodies. Immunotherapy using
      gammadelta T cells alone shows promising clinical activity, but there is a strong
      preclinical rationale for combining this treatment modality with cancer-targeting
      antibodies to augment its efficacy.

PMID- 24734217
TI  - Dasatinib promotes the expansion of a therapeutically superior T-cell repertoire
      in response to dendritic cell vaccination against melanoma.
AB  - Dasatinib (DAS) is a potent inhibitor of the BCR-ABL, SRC, c-KIT, PDGFR, and
      ephrin tyrosine kinases that has demonstrated only modest clinical efficacy in
      melanoma patients. Given reports suggesting that DAS enhances T cell infiltration
      into the tumor microenvironment, we analyzed whether therapy employing the
      combination of DAS plus dendritic cell (DC) vaccination would promote superior
      immunotherapeutic benefit against melanoma. Using a M05 (B16.OVA) melanoma mouse
      model, we observed that a 7-day course of orally-administered DAS (0.1 mg/day)
      combined with a DC-based vaccine (VAC) against the OVA257-264 peptide epitope
      more potently inhibited tumor growth and extended overall survival as compared
      with treatment with either single modality. The superior efficacy of the
      combinatorial treatment regimen included a reduction in hypoxic-signaling
      associated with reduced levels of immunosuppressive CD11b+Gr1+ myeloid-derived
      suppressor cells (MDSC) and CD4+Foxp3+ regulatory T (Treg) populations in the
      melanoma microenvironment. Furthermore, DAS + VAC combined therapy upregulated
      expression of Type-1 T cell recruiting CXCR3 ligand chemokines in the tumor
      stroma correlating with activation and recruitment of Type-1, vaccine-induced
      CXCR3+CD8+ tumor-infiltrating lymphocytes (TILs) and CD11c+ DC into the tumor
      microenvironment. The culmination of this bimodal approach was a profound
      "spreading" in the repertoire of tumor-associated antigens recognized by CD8+
      TILs, in support of the therapeutic superiority of combined DAS + VAC
      immunotherapy in the melanoma setting.

PMID- 24734218
TI  - Control of the adaptive immune response by tumor vasculature.
AB  - THE ENDOTHELIUM IS NOWADAYS DESCRIBED AS AN ENTIRE ORGAN THAT REGULATES VARIOUS
      PROCESSES: vascular tone, coagulation, inflammation, and immune cell trafficking,
      depending on the vascular site and its specific microenvironment as well as on
      endothelial cell-intrinsic mechanisms like epigenetic changes. In this review, we
      will focus on the control of the adaptive immune response by the tumor
      vasculature. In physiological conditions, the endothelium acts as a barrier
      regulating cell trafficking by specific expression of adhesion molecules enabling
      adhesion of immune cells on the vessel, and subsequent extravasation. This
      process is also dependent on chemokine and integrin expression, and on the type
      of junctions defining the permeability of the endothelium. Endothelial cells can
      also regulate immune cell activation. In fact, the endothelial layer can
      constitute immunological synapses due to its close interactions with immune
      cells, and the delivery of co-stimulatory or co-inhibitory signals. In tumor
      conditions, the vasculature is characterized by an abnormal vessel structure and
      permeability, and by a specific phenotype of endothelial cells. All these
      abnormalities lead to a modulation of intra-tumoral immune responses and
      contribute to the development of intra-tumoral immunosuppression, which is a
      major mechanism for promoting the development, progression, and treatment
      resistance of tumors. The in-depth analysis of these various abnormalities will
      help defining novel targets for the development of anti-tumoral treatments.
      Furthermore, eventual changes of the endothelial cell phenotype identified by
      plasma biomarkers could secondarily be selected to monitor treatment efficacy. 

PMID- 24734219
TI  - Cancer-associated fibroblasts as another polarized cell type of the tumor
      microenvironment.
AB  - Tumor- or cancer-associated fibroblasts (CAFs) are one of the most abundant
      stromal cell types in different carcinomas and comprise a heterogeneous cell
      population. Classically, CAFs are assigned with pro-tumorigenic effects
      stimulating tumor growth and progression. More recent studies demonstrated also
      tumor-inhibitory effects of CAFs suggesting that tumor-residing fibroblasts
      exhibit a similar degree of plasticity as other stromal cell types. Reciprocal
      interactions with the tumor milieu and different sources of origin are emerging
      as two important factors underlying CAF heterogeneity. This review highlights
      recent advances in our understanding of CAF biology and proposes to expand the
      term of cellular "polarization," previously introduced to describe different
      activation states of various immune cells, onto CAFs to reflect their phenotypic
      diversity. 

PMID- 24734220
TI  - Bacteriophages: an underestimated role in human and animal health?
AB  - Metagenomic approaches applied to viruses have highlighted their prevalence in
      almost all microbial ecosystems investigated. In all ecosystems, notably those
      associated with humans or animals, the viral fraction is dominated by
      bacteriophages. Whether they contribute to dysbiosis, i.e., the departure from
      microbiota composition in symbiosis at equilibrium and entry into a state
      favoring human or animal disease is unknown at present. This review summarizes
      what has been learnt on phages associated with human and animal microbiota, and
      focuses on examples illustrating the several ways by which phages may contribute
      to a shift to pathogenesis, either by modifying population equilibrium, by
      horizontal transfer, or by modulating immunity. 

PMID- 24734221
TI  - New therapeutic approaches for treatment of tularaemia: a review.
AB  - Antibiotic treatment of tularaemia is based on a few drugs, including the
      fluoroquinolones (e.g., ciprofloxacin), the tetracyclines (e.g., doxycycline),
      and the aminoglycosides (streptomycin and gentamicin). Because no effective and
      safe vaccine is currently available, tularaemia prophylaxis following proven
      exposure to F. tularensis also relies on administration of antibiotics. A number
      of reasons make it necessary to search for new therapeutic alternatives: the
      potential toxicity of first-line drugs, especially in children and pregnant
      women; a high rate of treatment relapses and failures, especially for severe
      and/or suppurated forms of the disease; and the possible use of antibiotic
      resistant strains in the context of a biological threat. This review presents
      novel therapeutic approaches that have been explored in recent years to improve
      tularaemia patients' management and prognosis. These new strategies have been
      evaluated in vitro, in axenic media and cell culture systems and/or in animal
      models. First, the activities of newly available antibiotic compounds were
      evaluated against F. tularensis, including tigecycline (a glycylcycline),
      ketolides (telithromycin and cethromycin), and fluoroquinolones (moxifloxacin,
      gatifloxacin, trovafloxacin and grepafloxacin). The liposome delivery of some
      antibiotics was evaluated. The effect of antimicrobial peptides against F.
      tularensis was also considered. Other drugs were evaluated for their ability to
      suppress the intracellular multiplication of F. tularensis. The effects of the
      modulation of the innate immune response (especially via TLR receptors) on the
      course of F. tularensis infection was characterized. Another approach was the
      administration of specific antibodies to induce passive resistance to F.
      tularensis infection. All of these studies highlight the need to develop new
      therapeutic strategies to improve the management of patients with tularaemia.
      Many possibilities exist, some unexplored. Moreover, it is likely that new
      therapeutic alternatives that are effective against this intracellular pathogen
      could be, at least partially, extrapolated to other human pathogens. 

PMID- 24734222
TI  - N2-Phenyl-9-(hydroxyalkyl)guanines and related compounds are substrates for
      Herpes simplex virus thymidine kinases.
AB  - Herpes simplex virus (HSV) types 1 and 2 thymidine kinases (TK) are responsible
      for phosphorylation of antiherpes acyclonucleosides such as acyclovir (ACV) and 9
      (4-hydroxybutyl)guanine (HBG). Related compounds, the N2-phenyl-9
      (hydroxyalkyl)guanines, are devoid of direct antiviral activity, but potently
      inhibit the viral TKs and block viral reactivation from latency in vivo. The
      similarity in structure between the acyclonucleosides and TK inhibitors raised
      the question of the relevance of phosphorylation of certain of the latter analogs
      in their mechanisms of action. Using recombinant TKs and HPLC analysis of
      reaction mixtures, we report that the lead TK inhibitor N2-phenyl-9 -(4
      hydroxybutyl)guanine (HBPG) and its pentyl homolog (HPnPG) are excellent
      substrates for the enzymes, approaching the efficiency with which the natural
      substrate thymidine is phosphorylated, and significantly better than ACV or HBG.
      Other 9-hydroxyalkyl congeners are substrates for the enzymes, but with much
      poorer efficiency. HBPG triphosphate was a poor inhibitor of HSV DNA polymerase,
      the target of acyclonucleoside triphosphates, suggesting that phosphorylation of
      HBPG is not important in its mechanism of blocking viral reactivation in vivo.
      The fact that HBPG is an efficient substrate is consistent, however, with its
      binding mode based both on molecular modeling studies and x-ray structure of the
      HBPG:TK complex.

PMID- 24734223
TI  - Juvenile myelomonocytic leukemia: molecular pathogenesis informs current
      approaches to therapy and hematopoietic cell transplantation.
AB  - Juvenile myelomonocytic leukemia (JMML) is a rare childhood leukemia that has
      historically been very difficult to confidently diagnose and treat. The majority
      of patients ultimately require allogeneic hematopoietic cell transplantation
      (HCT) for cure. Recent advances in the understanding of the pathogenesis of the
      disease now permit over 90% of patients to be molecularly characterized. Pre-HCT
      management of patients with JMML is currently symptom-driven. However, evaluation
      of potential high-risk clinical and molecular features will determine which
      patients could benefit from pre-HCT chemotherapy and/or local control of splenic
      disease. Furthermore, new techniques to quantify minimal residual disease burden
      will determine whether pre-HCT response to chemotherapy is beneficial for long
      term disease-free survival. The optimal approach to HCT for JMML is unclear, with
      high relapse rates regardless of conditioning intensity. An ongoing clinical
      trial in the Children's Oncology Group will test if less toxic approaches can be
      equally effective, thereby shifting the focus to post-HCT immunomanipulation
      strategies to achieve long-term disease control. Finally, our unraveling of the
      molecular basis of JMML is beginning to identify possible targets for selective
      therapeutic interventions, either pre- or post-HCT, an approach which may
      ultimately provide the best opportunity to improve outcomes for this aggressive
      disease. 

PMID- 24734224
TI  - Engineered Human Muscle Tissue from Skeletal Muscle Derived Stem Cells and
      Induced Pluripotent Stem Cell Derived Cardiac Cells.
AB  - During development, cardiac and skeletal muscle share major transcription factors
      and sarcomere proteins which were generally regarded as specific to either
      cardiac or skeletal muscle but not both in terminally differentiated adult
      cardiac or skeletal muscle. Here, we investigated whether artificial muscle
      constructed from human skeletal muscle derived stem cells (MDSCs) recapitulates
      developmental similarities between cardiac and skeletal muscle. We constructed 3
      dimensional collagen-based engineered muscle tissue (EMT) using MDSCs (MDSC-EMT)
      and compared the biochemical and contractile properties with EMT using induced
      pluripotent stem (iPS) cell-derived cardiac cells (iPS-EMT). Both MDSC-EMT and
      iPS-EMT expressed cardiac specific troponins, fast skeletal muscle myosin heavy
      chain, and connexin-43 mimicking developing cardiac or skeletal muscle. At the
      transcriptional level, MDSC-EMT and iPS-EMT upregulated both cardiac and skeletal
      muscle-specific genes and expressed Nkx2.5 and Myo-D proteins. MDSC-EMT displayed
      intracellular calcium ion transients and responses to isoproterenol. Contractile
      force measurements of MDSC-EMT demonstrated functional properties of immature
      cardiac and skeletal muscle in both tissues. Results suggest that the EMT from
      MDSCs mimics developing cardiac and skeletal muscle and can serve as a useful in
      vitro functioning striated muscle model for investigation of stem cell
      differentiation and therapeutic options of MDSCs for cardiac repair.

PMID- 24734225
TI  - Physical properties of polyamide-12 versus PMMA denture base material.
AB  - OBJECTIVES: Polyamide-12 (PA) is a flexible material suited for denture bases and
      clasping. This study investigated its potential aging effects with a focus on
      surface roughness, color stability, and elasticity. METHODS: PA specimens
      (Valplast) of 40*10*2 mm and equally measuring PMMA specimens (Palapress) as
      control were fabricated. Color changes after storage in air, water, coffee, and
      red wine (n=10) were measured using the CIE L*a*b* color specification.
      Elasticity after thermocycling (1000, 3000, and 7000 cycles,  n=15) was measured
      by three-point bending testing. Mean surface roughness (Ra) was determined after
      storage in the liquids mentioned above and thermocycling (n=10). RESULTS: Tukey's
      HSD test (P<0.05) revealed statistically significant color changes of PA in red
      wine (DeltaE=4.27 after 12 days, DeltaE=6.90 after 12 days) and coffee
      (DeltaE=3.93 after 36 days) but no color changes in PMMA. Elastic modulus of PA
      was 845 MPa and not affected by thermocycling (Tukey's HSD test,  P>0.81). Dry
      specimens showed significantly decreased elasticity (P<0.001). Mean surface
      roughness (PA 0.20  MU m, PMMA 0.28  MU m) did not change significantly after
      thermocycling or storage (Mann-Whitney U-test,  0.16<P<0.65). SIGNIFICANCE: PA
      exhibited a higher susceptibility to discoloration than PMMA. Neither surface
      roughness nor elasticity of PA was altered by artificial aging.

PMID- 24734226
TI  - Durable expression of minicircle DNA-liposome-delivered androgen receptor cDNA in
      mice with hepatocellular carcinoma.
AB  - BACKGROUND: The most common gene-based cancer therapies involve the suppression
      of oncogenic molecules and enhancement of the expression of tumor-suppressor
      genes. Studies in noncancer disease animal models have shown that minicircle (MC)
      DNA vectors are easy to deliver and that the proteins from said MC-carrying DNA
      vectors are expressed over a long period of time. However, delivery of
      therapeutic genes via a liposome-mediated, MC DNA complex has never been tested
      in vascular-rich hepatocellular carcinoma (HCC). Liposome-mediated DNA delivery
      exhibits high in vivo transfection efficiency and minimal systemic immune
      response, thereby allowing for repetitive interventions. In this study, we
      evaluated the efficacy of delivering an MC-liposome vector containing a 3.2 kb
      androgen receptor (AR; HCC metastasis suppressor) cDNA into Hepatitis B Virus-
      (HBV-) induced HCC mouse livers. RESULTS: Protein expression and promoter
      luciferase assays revealed that liposome-encapsulated MC-AR resulted in abundant
      functional expression of AR protein (100 kD) for up to two weeks. The AR cDNA was
      also successfully delivered into normal livers and diseased livers, where it was
      persistently expressed. In both normal livers and livers with tumors, the
      expression of AR was detectable for up to 60 days. CONCLUSION: Our results show
      that an MC/liposome delivery system might improve the efficacy of gene therapy in
      patients with HCC.

PMID- 24734228
TI  - Osteoblasts growth behaviour on bio-based calcium carbonate aragonite
      nanocrystal.
AB  - Calcium carbonate (CaCO3) nanocrystals derived from cockle shells emerge to
      present a good concert in bone tissue engineering because of their potential to
      mimic the composition, structure, and properties of native bone. The aim of this
      study was to evaluate the biological response of CaCO3 nanocrystals on hFOB 1.19
      and MC3T3 E-1 osteoblast cells in vitro. Cell viability and proliferation were
      assessed by MTT and BrdU assays, and LDH was measured to determine the effect of
      CaCO3 nanocrystals on cell membrane integrity. Cellular morphology was examined
      by SEM and fluorescence microscopy. The results showed that CaCO3 nanocrystals
      had no toxic effects to some extent. Cell proliferation, alkaline phosphatase
      activity, and protein synthesis were enhanced by the nanocrystals when compared
      to the control. Cellular interactions were improved, as indicated by SEM and
      fluorescent microscopy. The production of VEGF and TGF-1 was also affected by the
      CaCO3 nanocrystals. Therefore, bio-based CaCO3 nanocrystals were shown to
      stimulate osteoblast differentiation and improve the osteointegration process. 

PMID- 24734227
TI  - Nitric oxide, oxidative stress, and p66Shc interplay in diabetic endothelial
      dysfunction.
AB  - Increased oxidative stress and reduced nitric oxide (NO) bioavailability play a
      causal role in endothelial cell dysfunction occurring in the vasculature of
      diabetic patients. In this review, we summarized the molecular mechanisms
      underpinning diabetic endothelial and vascular dysfunction. In particular, we
      focused our attention on the complex interplay existing among NO, reactive oxygen
      species (ROS), and one crucial regulator of intracellular ROS production, p66Shc
      protein.

PMID- 24734230
TI  - Strain diversity of Mycobacterium tuberculosis isolates from pulmonary
      tuberculosis patients in Afar pastoral region of Ethiopia.
AB  - Data on genotypic diversity of Mycobacterium tuberculosis complex (MTBC) is
      important to understand its epidemiology, human adaptation, clinical phenotypes,
      and drug resistance. This study aimed to characterize MTBC clinical isolates
      circulating in a predominantly pastoralist area in Ethiopia, a country where
      tuberculosis is the second leading cause of mortality. Culture of sputum samples
      collected from a total of 325 pulmonary TB suspects was done to isolate MTBC.
      Spoligotyping was used to characterize 105 isolates from culture positive slopes
      and the result was compared with an international database. Forty-four
      spoligotype patterns were observed to correspond to 35 shared-types (SITs)
      containing 96 isolates and 9 orphan patterns; 27 SITs containing 83 isolates
      matched a preexisting shared-type in the database, whereas 8 SITs (n = 13
      isolates) were newly created. A total of 19 SITs containing 80 isolates were
      clustered within this study (overall clustering of 76.19%). Three dominant
      lineages (T, CAS, and Manu) accounted for 76.19% of the isolates. SIT149/T3-ETH
      was one of the two most dominant sublineages. Unlike previous reports, we show
      that Manu lineage strains not only constitute a dominant lineage, but are also
      associated with HIV infection in Afar region of Ethiopia. The high level of
      clustering suggests the presence of recent transmission that should be further
      studied using additional genotyping markers. 

PMID- 24734231
TI  - Characterization of musclin as a new target for treatment of hypertension.
AB  - Musclin is a novel skeletal muscle-derived factor found in the signal sequence
      trap of mouse skeletal muscle cDNAs. Recently, it has been demonstrated that
      musclin is involved in the pathogenesis of spontaneously hypertensive rats
      (SHRs). However, it is known as a genetic hypertension model. In the present
      study, we aim to investigate the role of musclin in another animal model of
      hypertension and characterize the direct effect of musclin on vascular
      contraction. The results show that expression of musclin was increased in
      arterial tissues isolated from DOCA-salt induced hypertensive rats or the normal
      rats received repeated vasoconstriction with phenylephrine. Additionally, direct
      incubation with phenylephrine did not modify the expression of musclin in the in
      vitro studies. Also, the direct effect of musclin on the increase of
      intracellular calcium was observed in a concentration-dependent manner. These
      results provide the evidence to support that musclin is involved in hypertension.
      Thus, musclin is suitable to be considered as a novel target for treatment of
      hypertension. 

PMID- 24734229
TI  - Role of methylglyoxal in Alzheimer's disease.
AB  - Alzheimer's disease is the most common and lethal neurodegenerative disorder. The
      major hallmarks of Alzheimer's disease are extracellular aggregation of amyloid
      beta peptides and, the presence of intracellular neurofibrillary tangles formed
      by precipitation/aggregation of hyperphosphorylated tau protein. The etiology of
      Alzheimer's disease is multifactorial and a full understanding of its
      pathogenesis remains elusive. Some years ago, it has been suggested that
      glycation may contribute to both extensive protein cross-linking and oxidative
      stress in Alzheimer's disease. Glycation is an endogenous process that leads to
      the production of a class of compounds known as advanced glycation end products
      (AGEs). Interestingly, increased levels of AGEs have been observed in brains of
      Alzheimer's disease patients. Methylglyoxal, a reactive intermediate of cellular
      metabolism, is the most potent precursor of AGEs and is strictly correlated with
      an increase of oxidative stress in Alzheimer's disease. Many studies are showing
      that methylglyoxal and methylglyoxal-derived AGEs play a key role in the
      etiopathogenesis of Alzheimer's disease. 

PMID- 24734232
TI  - Simple and cost-effective restriction endonuclease analysis of human
      adenoviruses.
AB  - Restriction endonuclease analyses (REAs) constitute the only inexpensive
      molecular approach capable of typing and characterizing human adenovirus (HAdV)
      strains based on the entire genome. However, the application of this method is
      limited by the need for time-consuming and labor-intensive procedures. We herein
      developed a simple and cost-effective REA for assessing HAdV. The method consists
      of (1) simple and cost-effective DNA extraction, (2) fast restriction
      endonuclease (RE) digestion, and (3) speedy mini agarose gel electrophoresis. In
      this study, DNA was isolated according to the kit-based method and 21.0 to 28.0 
      MUg of viral DNA was extracted from prototypes (HAdV-1, HAdV-3, HAdV-4, and HAdV
      37) in each flask. The amount of DNA ranged from 11.4 to 57.0  MUg among the HAdV
      3 (n=73) isolates. The obtained viral DNA was found to be applicable to more than
      10 types of REAs. Fast-cut restriction endonucleases (REs) were able to digest
      the DNA within 15 minutes, and restriction fragments were easily separated via
      horizontal mini agarose gel electrophoresis. The whole procedure for 10 samples
      can be completed within approximately six hours (the conventional method requires
      at least two days). These results show that our REA is potentially applicable in
      many laboratories in which HAdVs are isolated.

PMID- 24734233
TI  - A preliminary study of the influence of age of onset and childhood trauma on
      cortical thickness in major depressive disorder.
AB  - BACKGROUND: Major depressive disorder (MDD) neural underpinnings may differ based
      on onset age and childhood trauma. We assessed cortical thickness in patients who
      differed in age of MDD onset and examined trauma history influence. METHODS:
      Adults with MDD (N=36) and controls (HC; N=18) underwent magnetic resonance
      imaging. Twenty patients had MDD onset<24 years of age (pediatric onset) and 16
      had onset>25 years of age (adult onset). The MDD group was also subdivided into
      those with (N=12) and without (N=19) physical and/or sexual abuse as assessed by
      the Childhood Trauma Questionnaire (CTQ). Cortical thickness was analyzed with
      FreeSurfer software. RESULTS: Thicker frontal pole and a tendency for thinner
      transverse temporal cortices existed in MDD. The former was driven by the
      pediatric onset group and abuse history (independently), particularly in the
      right frontal pole. Inverse correlations existed between CTQ scores and frontal
      pole cortex thickness. A similar inverse relation existed with left inferior and
      right superior parietal cortex thickness. The superior temporal cortex tended to
      be thinner in pediatric versus adult onset groups with childhood abuse.
      CONCLUSIONS: This preliminary work suggests neural differences between pediatric
      and adult MDD onset. Trauma history also contributes to cytoarchitectural
      modulation. Thickened frontal pole cortices as a compensatory mechanism in MDD
      warrant evaluation.

PMID- 24734235
TI  - The dopaminergic reward system and leisure time exercise behavior: a candidate
      allele study.
AB  - PURPOSE: Twin studies provide evidence that genetic influences contribute
      strongly to individual differences in exercise behavior. We hypothesize that part
      of this heritability is explained by genetic variation in the dopaminergic reward
      system. Eight single nucleotide polymorphisms (SNPs in DRD1: rs265981, DRD2:
      rs6275, rs1800497, DRD3: rs6280, DRD4: rs1800955, DBH: rs1611115, rs2519152, and
      in COMT: rs4680) and three variable number of tandem repeats (VNTRs in DRD4,
      upstream of DRD5, and in DAT1) were investigated for an association with regular
      leisure time exercise behavior. MATERIALS AND METHODS: Data on exercise
      activities and at least one SNP/VNTR were available for 8,768 individuals aged 7
      to 50 years old that were part of the Netherlands Twin Register. Exercise
      behavior was quantified as weekly metabolic equivalents of task (MET) spent on
      exercise activities. Mixed models were fitted in SPSS with genetic relatedness as
      a random effect. RESULTS: None of the genetic variants were associated with
      exercise behavior (P>.02), despite sufficient power to detect small effects.
      DISCUSSION AND CONCLUSIONS: We did not confirm that allelic variants involved in
      dopaminergic function play a role in creating individual differences in exercise
      behavior. A plea is made for large genome-wide association studies to unravel the
      genetic pathways that affect this health-enhancing behavior.

PMID- 24734236
TI  - Acute kidney injury in neonates: from urine output to new biomarkers.
AB  - In the past 10 years, great effort has been made to define and classify a common
      syndrome previously known as acute renal failure and now renamed "acute kidney
      injury (AKI)." Initially suggested and validated in adult populations, AKI
      classification was adapted to the pediatric population and recently has been
      modified for the neonatal population. Several studies have been performed in
      adults and older children using this consensus definition, leading to improvement
      in the knowledge of AKI incidence and epidemiology. In spite of these advances,
      the peculiar renal pathophysiology of critically ill newborn patients makes it
      difficult to interpret urine output (UO) and serum creatinine (SCr) levels in
      these patients to diagnose AKI. Also, new urine biomarkers have emerged as a
      possible alternative to diagnose early AKI in the neonatal population. In this
      review, we describe recent advances in neonatal AKI epidemiology, discuss
      difficulties in diagnosing AKI in newborns, and show recent advances in new AKI
      biomarkers and possible long-term consequences after AKI episode. 

PMID- 24734237
TI  - Does intraoperative ulinastatin improve postoperative clinical outcomes in
      patients undergoing cardiac surgery: a meta-analysis of randomized controlled
      trials.
AB  - INTRODUCTION: The systematic meta-analysis of randomized controlled trials (RCTs)
      evaluated the effects of intraoperative ulinastatin on early-postoperative
      recovery in patients undergoing cardiac surgery. METHODS: RCTs comparing
      intraoperative ulinastatin with placebo in cardiac surgery were searched through
      PubMed, Cochrane databases, Medline, SinoMed, and the China National Knowledge
      Infrastructure (1966 to May 20th, 2013). The primary endpoints included hospital
      mortality, postoperative complication rate, length of stay in intensive care
      unit, and extubation time. The physiological and biochemical parameters
      illustrating postoperative cardiac and pulmonary function as well as inflammation
      response were considered as secondary endpoints. RESULTS: Fifteen RCTs (509
      patients) met the inclusion criteria. Ulinastatin did not affect hospital
      mortality, postoperative complication rate, or ICU length of stay but reduced
      extubation time. Ulinastatin also increased the oxygenation index on
      postoperative day 1 and reduced the plasma level of cardiac troponin-I.
      Additionally, ulinastatin inhibited the increased level of tumor necrosis factor
      alpha, polymorphonuclear neutrophil elastase, interleukin-6, and interleukin-8
      associated with cardiac surgery. CONCLUSION: Ulinastatin may be of value for the
      inhibition of postoperative increased inflammatory agents and most likely
      provided pulmonary protective effects in cardiac surgery. However, larger
      adequately powered RCTs are required to define the clinical effect of ulinastatin
      on postoperative outcomes in cardiac surgery.

PMID- 24734238
TI  - Effects of growth phase and temperature on sigmaB activity within a Listeria
      monocytogenes population: evidence for RsbV-independent activation of sigmaB at
      refrigeration temperatures.
AB  - The alternative sigma factor sigmaB of Listeria monocytogenes is responsible for
      regulating the transcription of many of the genes necessary for adaptation to
      both food-related stresses and to conditions found within the gastrointestinal
      tract of the host. The present study sought to investigate the influence of
      growth phase and temperature on the activation of sigmaB within populations of L.
      monocytogenes EGD-e wild-type, DeltasigB, and DeltarsbV throughout growth at both
      4 degrees C and 37 degrees C, using a reporter fusion that couples expression of
      EGFP to the strongly sigmaB-dependent promoter of lmo2230. A similar sigmaB
      activation pattern within the population was observed in wt-egfp at both
      temperatures, with the highest induction of sigmaB occurring in the early
      exponential phase of growth when the fluorescent population rapidly increased,
      eventually reaching the maximum in early stationary phase. Interestingly,
      induction of sigmaB activity was heterogeneous, with only a proportion of the
      cells in the wt-egfp population being fluorescent above the background
      autofluorescence level. Moreover, significant RsbV-independent activation of
      sigmaB was observed during growth at 4 degrees C. This result suggests that an
      alternative route to sigmaB activation exists in the absence of RsbV, a finding
      that is not explained by the current model for sigmaB regulation.

PMID- 24734239
TI  - Disruption of lipid rafts interferes with the interaction of Toxoplasma gondii
      with macrophages and epithelial cells.
AB  - The intracellular parasite Toxoplasma gondii can penetrate any warm-blooded
      animal cell. Conserved molecular assemblies of host cell plasma membranes should
      be involved in the parasite-host cell recognition. Lipid rafts are well-conserved
      membrane microdomains that contain high concentrations of cholesterol,
      sphingolipids, glycosylphosphatidylinositol, GPI-anchored proteins, and dually
      acylated proteins such as members of the Src family of tyrosine kinases.
      Disturbing lipid rafts of mouse peritoneal macrophages and epithelial cells of
      the lineage LLC-MK2 with methyl-beta cyclodextrin (M beta CD) and filipin, which
      interfere with cholesterol or lidocaine, significantly inhibited internalization
      of T. gondii in both cell types, although adhesion remained unaffected in
      macrophages and decreased only in LLC-MK2 cells. Scanning and transmission
      electron microscopy confirmed these observations. Results are discussed in terms
      of the original role of macrophages as professional phagocytes versus the LLC-MK2
      cell lineage originated from kidney epithelial cells. 

PMID- 24734240
TI  - Toxic damage increases angiogenesis and metastasis in fibrotic livers via PECAM
      1.
AB  - Excessive ethanol consumption is one of the main causes of liver fibrosis.
      However, direct effects of ethanol exposure on endothelial cells and their
      contribution to fibrogenesis and metastasis were not investigated. Therefore we
      analysed whether ethanol directly affects endothelial cells and if this plays a
      role during fibrogenesis and metastasis in the liver. Murine and human
      endothelial cells were exposed to ethanol for up to 72 hours. In vitro, effects
      on VEGF, HIF-1alpha, PECAM-1, and endothelial cell functions were analysed. In
      vivo, effects of continuous liver damage on blood vessel formation and metastasis
      were analysed by PECAM-1 immunohistochemistry. Ethanol increased HIF-1alpha and
      VEGF levels in murine and human endothelial cells. This resulted in enhanced
      intracellular signal transduction, and PECAM-1 expression as well as tube
      formation and wound healing. In vivo, toxic liver damage increased angiogenesis
      during fibrogenesis. Metastasis was also enhanced in fibrotic livers and located
      to PECAM-1 positive blood vessels compared to nonfibrotic mice. In conclusion,
      ethanol had strong effects on endothelial cells, which--at least in part--led to
      a profibrotic and prometastatic environment mediated by PECAM-1. Blockade of
      increased PECAM-1 expression could be a promising tool to inhibit fibrogenesis
      and metastasis in the liver.

PMID- 24734241
TI  - Peri- and postanalgesic properties of lidokain, lornoxicam, and nitroglycerine
      combination at intravenous regional anesthesia.
AB  - BACKGROUND: This study was conducted to compare and evaluate the effect of adding
      lornoxicam or nitroglycerine as adjuncts to lidocaine in intravenous regional
      anesthesia (IVRA). METHODS: 60 patients were randomly separated into three
      groups, lidocaine group (group L), lidocaine+lornoxicam group (group LL), and
      lidocaine+lornoxicam+transdermal nitroglycerine group (group LL-N). Hemodynamic
      parameters, sensory and motor blocks onset, and recovery times were recorded.
      Analgesic consumption for tourniquet pain and postoperative period were recorded.
      RESULTS: Sensory block onset times and motor block onset times were shorter in
      the LL-N and LL groups compared with L group. Sensory block recovery time and
      motor block recovery time were prolonged in the LL and LL-N groups compared with
      group L. The amount of fentanyl required for tourniquet pain was less in group LL
      and group LL-N when compared with group L. VAS scores of tourniquet pain were
      higher in group L compared with the other study groups. Postoperative VAS scores
      were higher for the first 4 hours in group L compared with the other study
      groups. CONCLUSION: The adjuvant drugs (lornoxicam or TNG) when added to
      lidocaine in IVRA were effective in improving the overall quality of anesthesia,
      reducing tourniquet pain, increasing tourniquet tolerance, and improving the
      postoperative analgesia.

PMID- 24734242
TI  - Role of G protein-coupled receptors in control of dendritic cell migration.
AB  - Dendritic cells (DCs) are highly efficient antigen-presenting cells. The
      migratory properties of DCs give them the capacity to be a sentinel of the body
      and the vital role in the induction and regulation of adaptive immune responses.
      Therefore, it is important to understand the mechanisms in control of migration
      of DCs to lymphoid and nonlymphoid tissues. This may provide us novel insight
      into the clinical treatment of diseases such as autoimmune disease, infectious
      disease, and tumor. The chemotactic G protein-coupled receptors (GPCR) play a
      vital role in control of DCs migration. Here, we reviewed the recent advances
      regarding the role of GPCR in control of migration of subsets of DCs, with a
      focus on the chemokine receptors. Understanding subsets of DCs migration could
      provide a rational basis for the design of novel therapies in various clinical
      conditions. 

PMID- 24734244
TI  - Effect of video-based versus personalized instruction on errors during elastic
      tubing exercises for musculoskeletal pain: a randomized controlled trial.
AB  - Workplace interventions have shown beneficial results of resistance training for
      chronic pain in the neck, shoulder, and arm. However, studies have relied on
      experienced exercise instructors, which may not be an available resource at most
      workplaces. The objective of this study is to evaluate the technical performance
      level of upper limb rehabilitation exercises following video-based versus
      personalized exercise instruction. We recruited 38 laboratory technicians and
      office workers with neck/shoulder pain for a two-week exercise training period
      receiving either (1) personal and video or (2) video only instruction in four
      typical neck/shoulder/arm rehabilitation exercises using elastic tubing. At a 2
      week follow-up, the participants' technical execution was assessed by two blinded
      physical therapists using a reliable error assessment tool. The error assessment
      was based on ordinal deviation of joint position from the ideal position of the
      shoulder, elbow, and wrist in a single plane by visual observation. Of the four
      exercises only unilateral shoulder external rotation had a higher normalized
      error score in the V group of 22.19 (9.30) to 12.64 (6.94) in the P group
      (P=0.002). For the remaining three exercises the normalized error score did not
      differ. In conclusion, when instructing simple exercises to reduce
      musculoskeletal pain the use of video material is a cost-effective solution that
      can be implemented easily in corporations with challenging work schedules not
      allowing for a fixed time of day to go see a personal trainer.

PMID- 24734243
TI  - Estrogen Deficiency and the Origin of Obesity during Menopause.
AB  - Sex hormones strongly influence body fat distribution and adipocyte
      differentiation. Estrogens and testosterone differentially affect adipocyte
      physiology, but the importance of estrogens in the development of metabolic
      diseases during menopause is disputed. Estrogens and estrogen receptors regulate
      various aspects of glucose and lipid metabolism. Disturbances of this metabolic
      signal lead to the development of metabolic syndrome and a higher cardiovascular
      risk in women. The absence of estrogens is a clue factor in the onset of
      cardiovascular disease during the menopausal period, which is characterized by
      lipid profile variations and predominant abdominal fat accumulation. However,
      influence of the absence of these hormones and its relationship to higher obesity
      in women during menopause are not clear. This systematic review discusses of the
      role of estrogens and estrogen receptors in adipocyte differentiation, and its
      control by the central nervous systemn and the possible role of estrogen-like
      compounds and endocrine disruptors chemicals are discussed. Finally, the
      interaction between the decrease in estrogen secretion and the prevalence of
      obesity in menopausal women is examined. We will consider if the absence of
      estrogens have a significant effect of obesity in menopausal women. 

PMID- 24734245
TI  - Digging up the human genome: current progress in deciphering adverse drug
      reactions.
AB  - Adverse drug reactions (ADRs) are a major clinical problem. In addition to their
      clinical impact on human health, there is an enormous cost associated with ADRs
      in health care and pharmaceutical industry. Increasing studies revealed that
      genetic variants can determine the susceptibility of individuals to ADRs. The
      development of modern genomic technologies has led to a tremendous advancement of
      improving the drug safety and efficacy and minimizing the ADRs. This review will
      discuss the pharmacogenomic techniques used to unveil the determinants of ADRs
      and summarize the current progresses concerning the identification of biomarkers
      for ADRs, with a focus on genetic variants for genes encoding drug-metabolizing
      enzymes, drug-transporter proteins, and human leukocyte antigen (HLA). The
      knowledge gained from these cutting-edge findings will form the basis for better
      prediction and management for ADRs, ultimately making the medicine personalized. 

PMID- 24734246
TI  - Quantitative elastography for cervical stiffness assessment during pregnancy.
AB  - AIM: Feasibility and reliability of tissue Doppler imaging-(TDI-) based
      elastography for cervical quantitative stiffness assessment during all three
      trimesters of pregnancy were evaluated. MATERIALS AND METHODS: Prospective case
      control study including seventy-four patients collected between the 12th and 42nd
      weeks of gestation. The tissue strain (TS) was measured by two independent
      operators as natural strain. Intra- and interoperator intraclass correlation
      coefficient (ICC) agreements were evaluated. RESULTS: TS measurement was always
      feasible and exhibited a high performance in terms of reliability (intraoperator
      ICC-agreement=0.93; interoperator ICC agreement=0.89 and 0.93 for a single
      measurement and for the average of two measurements, resp.). Cervical TS showed
      also a significant correlation with gestational age, cervical length, and parity.
      CONCLUSIONS: TS measurement during pregnancy demonstrated high feasibility and
      reliability. Furthermore, TS significantly correlated with gestational age,
      cervical length, and parity.

PMID- 24734247
TI  - Lasting effects of workplace strength training for neck/shoulder/arm pain among
      laboratory technicians: natural experiment with 3-year follow-up.
AB  - OBJECTIVES: This study investigated long-term effects and implementation
      processes of workplace strength training for musculoskeletal disorders. METHODS:
      333 and 140 laboratory technicians from private and public sector companies,
      respectively, replied to a 3-year follow-up questionnaire subsequent to a 1-year
      randomized controlled trial (RCT) with high-intensity strength training for
      prevention and treatment of neck, shoulder, and arm pain. Being a natural
      experiment, the two participating companies implemented and modified the initial
      training program in different ways during the subsequent 2 years after the RCT.
      RESULTS: At 3-year follow-up the pain reduction in neck, shoulder, elbow, and
      wrist achieved during the first year was largely maintained at both companies.
      However, the private sector company was rated significantly better than the
      public sector company in (1) training adherence, (2) training culture, that is,
      relatively more employees trained at the workplace and with colleagues, (3) self
      reported health changes, and (4) prevention of neck and wrist pain development
      among initially pain-free employees. CONCLUSIONS: This natural experiment shows
      that strength training can be implemented successfully at different companies
      during working hours on a long-term basis with lasting effects on pain in neck,
      shoulder, and arm.

PMID- 24734248
TI  - Cumulative delivery rate after providing full reimbursement in vitro
      fertilization programme: a 6-years survey.
AB  - Since 1983, Slovenia has been offering well-established, successful, and fully
      reimbursed IVF programme to infertile couples. On the grounds of data gathered at
      the Slovenian IVF units we aimed to determine whether the fully accessible IVF
      treatment system can provide notable success considering cumulative delivery rate
      (cDR). Longitudinal analysis of getting cDR was performed in 810 IVF cycles of
      395 couples who for the first time attended the IVF programme in year 2006 and
      were followed until year 2012. We calculated the actual and the optimistic cDR.
      In women aged<38 years the actual cDR was 54% and optimistic DR was 83%,
      respectively. In women aged>=38 years the actual cDR was 24% and optimistic cDR
      was 27%. These results enable us to report that prospects of the treatment for
      the women aged<38 years, if they undergo all 6 available IVF cycles, are very
      positive and quite comparable to the chances of spontaneous conception. Even in
      older patients it is beneficial to repeat the IVF procedures. Therefore we
      consider the existing infertility treatment system in Slovenia as an example of
      good medical practice with high level of beneficence offered to the patients.

PMID- 24734249
TI  - Dynamics of blood count after rheohemapheresis in age-related macular
      degeneration: possible association with clinical changes.
AB  - BACKGROUND: Rheohemapheresis (RHF) is a method that can stop the activity of the
      dry form of age-related macular degeneration (AMD). The pathophysiologic
      mechanisms are not well understood, and the effects of the RHF procedures extend
      beyond the time of the individual procedures. PATIENTS AND METHODS: We present
      the data for 46 patients with AMD treated with a series of 8 rheohemapheretic
      procedures. Blood count parameters were measured before the first and the last
      procedures. The clinical effect was judged by changes in the drusenoid pigment
      epithelium detachment (DPED) area before and after the rheopheretic sessions.
      RESULTS: Rheopheresis caused a decrease in hemoglobin (P<0.001), a decrease in
      leukocytes (P<0.034), and an increase in platelets (P<0.005). We found a negative
      correlation between the amount of platelets and their volume (P<0.001, Pearson
      correlation coefficient: -0.509). We identified the platelet/MPV ratio as a good
      predictor of the clinical outcome. Patients with a platelet/MPV ratio greater
      than 21.5 (before the last rheopheresis) had a significantly better outcome
      (P=0.003, sensitivity of 76.9% and specificity of 80%). CONCLUSION: Several basic
      blood count parameters after RHF can be concluded to significantly change, with
      some of those changes correlating with the clinical results (reduction of the
      DPED area).

PMID- 24734250
TI  - Contrast-induced acute kidney injury: definition, epidemiology, and outcome.
AB  - Contrast-induced acute kidney injury (CI-AKI) is commonly defined as a decline in
      kidney function occurring in a narrow time window after administration of
      iodinated contrast material. The incidence of AKI after contrast material
      administration greatly depends on the specific definition and cutoff values used.
      Although self-limiting in most cases, postcontrast AKI carries a risk of more
      permanent renal insufficiency, dialysis, and death. The risk of AKI from contrast
      material, in particular when administered intravenously for contrast-enhanced CT,
      has been exaggerated by older, noncontrolled studies due to background
      fluctuations in renal function. More recent evidence from controlled studies
      suggests that the risk is likely nonexistent in patients with normal renal
      function, but there may be a risk in patients with renal insufficiency. However,
      even in this patient population, the risk of CI-AKI is probably much smaller than
      traditionally assumed. Since volume expansion is the only preventive strategy
      with a convincing evidence base, liberal hydration should be encouraged to
      further minimize the risk. The benefits of the diagnostic information gained from
      contrast-enhanced examinations will still need to be balanced with the potential
      risk of CI-AKI for the individual patient and clinical scenario. 

PMID- 24734251
TI  - Anti-CD133 antibody immobilized on the surface of stents enhances
      endothelialization.
AB  - Drug eluting stents successfully reduce restenosis at the cost of delayed
      reendothelialization. In recent years, a novel concept to enhance
      reendothelialization using anti-CD34 antibody coated stents which capture
      circulating progenitor cells (EPCs) has been developed with conflicting clinical
      results. CD133 is a glycoprotein expressed on circulating hematopoietic and
      putative endothelial-regenerating cells and may be superior to CD34 for EPCs
      capture stents. In the present study, anti-CD133 antibody has been successfully
      immobilized to the biodegradable polymeric coating material by covalent
      conjugation. We explore whether anti-CD133 antibody coated stents (CD133 stents)
      might accelerate reendothelialization in comparison with bare metal stents (BMS)
      through the superior ability to capture EPCs. The in vitro cell culture results
      indicate that anti-CD133 antibody functionalized polymer film significantly
      promotes CD133 positive cells attachment and growth compared with the
      unfunctionalized polymer film. In the semi-in vivo arteriovenous shunt model
      CD133 stents demonstrate much quicker specific capturing of EPCs from the blood
      stream than BMS within 6 hours. In a porcine coronary artery injury model CD133
      stents show more effective reendothelialization in short term compared with BMS,
      while no significant difference in endothelial function recovery was observed
      between these two groups within 6-month followup. 

PMID- 24734252
TI  - Effect of chromium on antioxidant potential of Catharanthus roseus varieties and
      production of their anticancer alkaloids: vincristine and vinblastine.
AB  - Catharanthus roseus (L.) G. Don, a medicinal plant, has a very important place in
      the traditional as well as modern pharmaceutical industry. Two common varieties
      of this plant rosea and alba are named so because of pink and white coloured
      flowers, respectively. This plant comprises of about 130 terpenoid indole
      alkaloids and two of them, vincristine and vinblastine, are common anticancer
      drugs. The effect of chromium (Cr) on enzymatic and non-enzymatic antioxidant
      components and on secondary metabolites vincristine and vinblastine was studied
      under pot culture conditions of both varieties of C. roseus. Antioxidant
      responses of these varieties were analyzed under 0, 10, 50, and 100  MUM chromium
      (Cr) level in order to investigate the plant's protective mechanisms against Cr
      induced oxidative stress. The results indicated that Cr affects all the studied
      parameters and decreases growth performance. However, vincristine and vinblastine
      contents were increased under Cr stress. Results are quite encouraging, as this
      plant shows good antioxidant potential and increased the level of active
      constituents under Cr stress.

PMID- 24734253
TI  - Mercury speciation in hair of children in three communities of the Amazon,
      Brazil.
AB  - Children from riverside communities located downstream of gold mining areas may
      be chronically exposed to relatively high levels of MeHg through the consumption
      of fish of this region. The objective of this study was to evaluate and compare
      levels of THg and MeHg in hair of children less than 12 years in communities near
      mines in the municipality of Itaituba and in communities far from prospecting
      areas in the city of Abaetetuba. The communities of Itaituba (Barreiras and Sao
      Luiz do Tapajos) had THg mean levels of 5.64+/-5.55  MUg.g(-1) (0.43-27.82) and
      11.41+/-7.16  MUg.g(-1) (1.08-28.17), respectively, and an average count of MeHg
      relative to THg of 92.20% and 90.27%, respectively. In the Maranhao community,
      the THg average concentrations results were 2.27+/-2.11  MUg.g(-1) (0.13-9.54)
      and the average values were 93.17% for MeHg. Children of Itaituba had average
      levels of mercury above the limit established by the World Health Organization
      (10  MUg.g(-1)) and the strong correlation coefficient between the communities
      (R=0.968 and P=0.0001) suggests the hair as an excellent biomarker of human
      exposure to organic mercury in riverside populations of the Tapajos, which has
      the intake of fish daily as main source of protein dietary.

PMID- 24734254
TI  - Commentary on the regulation of viral proteins in autophagy process.
AB  - The ability to subvert intracellular antiviral defenses is necessary for virus to
      survive as its replication occurs only in the host cells. Viruses have to
      modulate cellular processes and antiviral mechanisms to their own advantage
      during the entire virus life cycle. Autophagy plays important roles in cell
      regulation. Its function is not only to catabolize aggregate proteins and damaged
      organelles for recycling but also to serve as innate immunity to remove
      intracellular pathogenic elements such as viruses. Nevertheless, some viruses
      have evolved to negatively regulate autophagy by inhibiting its formation. Even
      more, some viruses have employed autophagy to benefit their replication. To date,
      there are more and more growing evidences uncovering the functions of many viral
      proteins to regulate autophagy through different cellular pathways. In this
      review, we will discuss the relationship between viruses and autophagy and
      summarize the current knowledge on the functions of viral proteins contributing
      to affect autophagy process. 

PMID- 24734256
TI  - P38 plays an important role in glucolipotoxicity-induced apoptosis in INS-1
      cells.
AB  - OBJECTIVES: The mechanism underlying the regulation of glucolipotoxicity-induced
      apoptosis by MAPKs was examined in INS-1 cells. METHODS: The rat insulinoma cell
      line INS-1 was cotreated with glucose (30 mM) and palmitic acid (0.2 mM)
      (GLU+PA). Apoptosis was assessed by cell morphology and detection of PARP
      cleavage. The activation of MAPKs was examined by Western blotting using specific
      antibodies against the phosphorylated forms of JNK, ERK1/2, and P38. RESULTS: (1)
      Live cell imaging studies showed that treatment with GLU+PA for 72 h induced
      significant cell death, concomitant with PARP-1 cleavage and caspase-3
      activation, which peaked at 96 h of treatment. (2) Western blot analysis of the
      activation of MAPKs during GLU+PA-induced INS-1 cell apoptosis showed that
      phosphorylation of P38 increased gradually and reached a peak at 96 h, which
      coincided with PARP-1 cleavage. A transient increase of ERK activation was
      followed by a rapid decline at 96 h, whereas JNK phosphorylation status remained
      unchanged in response to GLU+PA. (3) Phosphorylation of insulin receptor
      substrate (IRS)-2 at 48 h of treatment triggered its degradation, which coincided
      with P38 activation. (4) Inhibition of P38, but not JNK or ERK, blocked GLU+PA
      induced INS-1 cell apoptosis. CONCLUSIONS: P38 may be involved in the regulation
      of glucolipotoxicity-induced apoptosis through the phosphorylation of IRS-2.

PMID- 24734257
TI  - Xin Scaffolding Proteins and Arrhythmias.

PMID- 24734258
TI  - Marshall Nirenberg: after the genetic code and into neurobiology.

PMID- 24734259
TI  - Platon G. Kostyuk (August 20, 1924-May 10, 2010): A unique survey of a life
      spanning turbulent times.
AB  - On May 10th 2010 Platon Grigorevitch Kostyuk sadly left us at the age of 85. He
      was a talented scientist, a brilliant experimenter, an outstanding organizer of
      science and an excellent teacher. Platon Kostyuk was born in 1924 in Kiev,
      Ukraine. He obtained a double education: a graduate of the Kiev University
      Department of Biology in 1946 and the Kiev Medical Institute in 1949, he became a
      pioneer in neuroscience, the first in the Soviet Union to use microelectrodes for
      intracellular recording of electrical signals in neurons. Despite the
      difficulties for international travel for those living behind the Iron Curtain,
      he was able to present his work at the International Congress of Physiology in
      Buenos Aires in 1959 and here met Prof. John Eccles who invited him to work at
      the University of Canberra in Australia in 1960-1961. This was the start of an
      outstanding international career, complementing his creative achievements in the
      Soviet Union. In 1966 P.G. Kostyuk became director of the Bogomoletz Institute of
      Physiology in Kiev, which he headed for nearly 45 years. Under his direction this
      Institute became a leading centre for neuroscience, renowned not only in the
      Soviet Union but also internationally. New directions of research were developed
      in cell physiology, molecular biophysics and neurophysiology. Several important
      discoveries were made including the development of a method for intracellular
      perfusion, evidence for a calcium-dependent conductance in nerve cells and the
      discovery of new types of ion channels. Elected to the Ukraine Academy of Science
      in 1969 and Grand Academician of the Soviet Academy of Science in 1974, Kostyuk
      has also been honoured by many international societies. He is the author of more
      than 650 articles, 17 monographs and 7 discoveries and was the creator and editor
      of two scientific journals: "Neurophysiology" and "Neuroscience". The outstanding
      career and multifaceted activities of Academician Platon Kostyuk form a pyramid
      of achievement, at the top of which ride his research in cognition and his
      enthusiasm for the discovery of the secrets of Nature.

PMID- 24734255
TI  - Role of microRNAs in islet beta-cell compensation and failure during diabetes.
AB  - Pancreatic beta-cell function and mass are markedly adaptive to compensate for
      the changes in insulin requirement observed during several situations such as
      pregnancy, obesity, glucocorticoids excess, or administration. This requires a
      beta-cell compensation which is achieved through a gain of beta-cell mass and
      function. Elucidating the physiological mechanisms that promote functional beta
      cell mass expansion and that protect cells against death, is a key therapeutic
      target for diabetes. In this respect, several recent studies have emphasized the
      instrumental role of microRNAs in the control of beta-cell function. MicroRNAs
      are negative regulators of gene expression, and are pivotal for the control of
      beta-cell proliferation, function, and survival. On the one hand, changes in
      specific microRNA levels have been associated with beta-cell compensation and are
      triggered by hormones or bioactive peptides that promote beta-cell survival and
      function. Conversely, modifications in the expression of other specific microRNAs
      contribute to beta-cell dysfunction and death elicited by diabetogenic factors
      including, cytokines, chronic hyperlipidemia, hyperglycemia, and oxidized LDL.
      This review underlines the importance of targeting the microRNA network for
      future innovative therapies aiming at preventing the beta-cell decline in
      diabetes. 

PMID- 24734260
TI  - The ecology of plant populations: their dynamics, interactions and evolution.

PMID- 24734261
TI  - On the intrinsic photophysics of indigo: a time-resolved photoelectron
      spectroscopy study of the indigo carmine dianion.
AB  - The intrinsic photophysics of indigo has been studied using gas-phase time
      resolved photoelectron imaging of the indigo carmine dianion (InC(2-)). The
      action spectrum reveals that the gas-phase absorption spectrum arising from the
      S(1) <-- S(0) transition in InC(2-) has a similar solvent shift to that of
      neutral indigo. Femtosecond spectroscopy shows that the S(1) state decays on a
      1.4 ps timescale. Through isotopic substitution, the primary mechanism on the
      S(1) excited state can be assigned to an intra-molecular proton transfer, which
      is the same as that which has been observed in solution. However, the excited
      state lifetime is significantly shorter in vacuum. These similarities and
      differences are discussed in terms of recent theoretical investigations of the
      S(1) excited state of indigo.

PMID- 24734262
TI  - Getting nurses to use evidence-based practice takes culture change.

PMID- 24734263
TI  - Nothing new doesn't mean nothing important.

PMID- 24734264
TI  - Creative efforts drive goals home.

PMID- 24734265
TI  - Call to Action wants more reporting.

PMID- 24734266
TI  - Sentinel event data show little change.

PMID- 24734267
TI  - The grass isn't always greener.

PMID- 24734269
TI  - Authors' reply.

PMID- 24734268
TI  - Authors' reply.

PMID- 24734270
TI  - Authors' reply.

PMID- 24734271
TI  - Jeffrey Bland, Phd, FACN, FACB: heart disease, inflammation, and the revolution
      in health care. Interview by Craig Gustafson.

PMID- 24734272
TI  - Identification of CDCA1-derived long peptides bearing both CD4+ and CD8+ T-cell
      epitopes: CDCA1-specific CD4+ T-cell immunity in cancer patients.
AB  - We recently identified a novel cancer-testis antigen, cell division cycle
      associated 1 (CDCA1) using genome-wide cDNA microarray analysis, and CDCA1
      derived cytotoxic T lymphocyte (CTL)-epitopes. In this study, we attempted to
      identify CDCA1-derived long peptides (LPs) that induce both CD4+ helper T (Th)
      cells and CTLs. We combined information from a recently developed computer
      algorithm predicting HLA class II-binding peptides with CDCA1-derived CTL-epitope
      sequences presented by HLA-A2 (A*02:01) or HLA-A24 (A*24:02) to select candidate
      CDCA1-LPs encompassing both Th cell epitopes and CTL-epitopes. We studied the
      immunogenicity of CDCA1-LPs and the cross-priming potential of LPs bearing CTL
      epitopes in both human in vitro and HLA-class I transgenic mice in vivo. Then we
      analyzed the Th cell response to CDCA1 in head-and-neck cancer (HNC) patients
      before and after vaccination with a CDCA1-derived CTL-epitope peptide using IFN
      gamma enzyme-linked immunospot assays. We identified two CDCA1-LPs, CDCA1(39-64)
      LP and CDCA1(55-78)-LP, which encompass naturally processed epitopes recognized
      by Th cells and CTLs. CDCA1-specific CTLs were induced through cross-presentation
      of CDCA1-LPs in vitro and in vivo. In addition, CDCA1-specific Th cells enhanced
      induction of CDCA1-specific CTLs. Furthermore, significant frequencies of CDCA1
      specific Th cell responses were detected after short-term in vitro stimulation of
      peripheral blood mononuclear cells (PBMCs) with CDCA1-LPs in HNC patients
      (CDCA1(39-64)-LP, 74%; CDCA1(55-78)-LP, 68%), but not in healthy donors. These
      are the first results demonstrating the presence of CDCA1-specific Th cell
      responses in HNC patients and underline the possible utility of CDCA1-LPs for
      propagation of both CDCA1-specific Th cells and CTLs.

PMID- 24734273
TI  - Commentary on 'Sequential cervical length screening in pregnancies after LLETZ
      conisation: a retrospective analysis'.

PMID- 24734274
TI  - Reply: To PMID 24111502.

PMID- 24734275
TI  - Attitudes of healthcare providers towards family involvement and presence in
      adult critical care units in Saudi Arabia: a quantitative study.
AB  - AIMS AND OBJECTIVES: To describe healthcare providers' attitudes to family
      involvement during routine care and family presence during resuscitation or other
      invasive procedures in adult intensive care units in Saudi Arabia. BACKGROUND:
      Previous research has shown that healthcare professionals have revealed a
      diversity of opinions on family involvement during routine care and family
      presence during resuscitation or other invasive procedures. Attitude assessment
      can provide an indication of staff acceptance or rejection of the practice and
      also help identify key potential barriers that will need to be addressed. It has
      also been evident that participation in the care has potential benefits for
      patients and families as well as healthcare providers. DESIGN: A quantitative
      descriptive design. METHODS: A questionnaire was used with a convenience sample
      of 468 healthcare providers who were recruited from eight intensive care units.
      RESULTS: The analysis found that healthcare providers had positive attitudes
      towards family involvement during routine care, but negative attitudes towards
      family presence during resuscitation or other invasive procedures. Physicians
      expressed more opposition to the practice than did nurses and respiratory
      therapists. Staff indicated a need to develop written guidelines and policies, as
      well as educational programmes, to address this sensitive issue in clinical
      practice. CONCLUSION: Family is an important resource in patient care in the
      context of the critical care environment. Clinical barriers including resources,
      hospital policies and guidelines, staff and public education should be taken into
      account to facilitate family integration to the care model. RELEVANCE TO CLINICAL
      PRACTICE: The findings can help to develop policies and guidelines for safe
      implementation of the practice. They can also encourage those who design nursing
      and other medical curricula to place more emphasis on the role of the family
      especially in critical care settings.

PMID- 24734276
TI  - Authors' reply.

PMID- 24734278
TI  - Retraction notice of: "Physical activity within a CBT intervention improves
      coping with pain in traumatized refugees: results of a randomized controlled
      design". Pain Med 2011;12:234-45.

PMID- 24734277
TI  - Higher risk of superficial injection during injection laryngoplasty in women.
AB  - PURPOSE: To review our clinical experience with percutaneous injection
      laryngoplasty at a single institution over a three-year period, and to
      specifically assess the rate of unintentional injection into the superficial
      lamina propria (SLP) and compare with results found in the literature. MATERIALS
      AND METHODS: Medical records were retrospectively reviewed to identify patients
      who underwent office-based injection laryngoplasty (OBIL) over a three-year
      period. Video documentation and the written notes of the procedures were reviewed
      to determine the rate of inadvertent placement of injectate into the SLP. A
      literature review was performed to identify other reports of this complication
      and contributing factors. RESULTS: 113 consecutive patients were identified who
      underwent OBIL in the study period. Of these, 100 patients had adequate records
      and follow-up available for this review. All patients underwent injection
      augmentation with bovine collagen using a percutaneous trans-membrane or trans
      cartilaginous technique. 96 had improvement in their vocal quality and/or effort.
      Four patients, who were all women, had unintentional injection into the SLP with
      resultant no change in voice or worsened voice. All superficially placed
      injectates were managed conservatively. CONCLUSIONS: Injection into the SLP is a
      well-recognized possible complication of OBIL. Our results suggest that this
      complication occurs more often in women than in men, perhaps due to differing
      laryngeal anatomy and size.

PMID- 24734279
TI  - Differential Release Kinetics of Cardiac Biomarkers in Patients Undergoing Valve
      Replacement Surgery.
AB  - BACKGROUND: Differential release kinetics of cardiac biomarkers including brain
      natriuretic peptide (BNP), Troponin-I, and CK-MB following valve replacement (VR)
      are not well characterized. METHODS AND RESULTS: We serially measured these
      biomarkers 24 hours prior, six hours, 24 hours, 48 hours, and one month following
      mitral/aortic VR in 100 patients. Baseline BNP, Tn-I, and CK-MB levels were
      304.01 pg/mL, 0.03 ng/mL, and 0.99 ng/mL, respectively. While BNP levels
      decreased at six hours, and then peaked at 24 hours, Tn-I and CK-MB levels
      increased within six hours and then showed declining trends by 24 hours. While Tn
      I and CK-MB levels normalized at one month, 33% patients still had BNP >200
      pg/mL. Those with baseline BNP >200 pg/mL more commonly had AF, higher RV
      systolic pressure, longer inotrope and ventilator duration, and longer mean
      ICU/hospital stay as compared to those with lower BNP, although echocardiographic
      left ventricular ejection fraction and Tn-I/CK-MB levels were similar. Inotrope
      duration >42 hours, ventilation time >29 hours, and ICU stay >4 days was seen in
      42% versus 19%, 30% versus 9%, and 33% versus 14%, respectively, in those with
      BNP >/<200 pg/mL. Baseline BNP had a significant positive correlation with mean
      inotrope duration, ICU, and hospital stay. Baseline BNP was also a significant
      predictor of inotrope duration (odds ratio [OR]=5.9, 95% confidence interval
      [CI]=1.20-29.68, p=0.01) and ventilation time (OR=4.7, 95% CI=1.76-17.21,
      p=0.02). CONCLUSION: Release kinetics of cardiac biomarkers is significantly
      different following VR; BNP levels increase following an initial transient
      decline. Only BNP was a predictor of postoperative variables.

PMID- 24734280
TI  - Predictors of prognosis in patients with mild to moderate paravalvular leakage
      after mitral valve replacement.
AB  - BACKGROUND: The aim of this study was to evaluate predictors of clinical events
      in patients with mild to moderate paravalvular leakage (PVL) after mitral valve
      replacement (MVR). METHODS AND RESULTS: We retrospectively reviewed all the
      medical records and echocardiography of 60 patients with PVL after MVR. After
      excluding 18 patients who required immediate surgical repair for severe symptoms
      or regurgitation and four patients with severe anemia who required transfusion,
      two patients with concomitant infective endocarditis, two patients with severe
      stenosis or regurgitation of other valves, and one patient with severe left
      ventricular systolic dysfunction, the remaining 33 patients who were not
      indicated for reoperation or immediate blood transfusion comprised the study
      population. During a median follow-up period of 19 months, there were 18 events,
      including two cardiac deaths, one noncardiac death, 13 repeat surgeries, and two
      admissions for heart failure. Cox regression analysis revealed that the presence
      of hemolytic anemia at the diagnosis of PVL was the only independent predictor of
      event-free survival (p=0.035). The estimated three-year event-free survival rates
      were 78 +/- 12% in patients without hemolytic anemia and 16 +/- 10% in those with
      hemolytic anemia (p=0.004). CONCLUSION: Presence of hemolytic anemia was
      associated with poor short-term clinical outcome in mild to moderate PVL after
      MVR, even in the cases when the degree of anemia was not severe at the time of
      diagnosis. Therefore, in PVL patients after MVR with hemolytic anemia, more early
      aggressive therapeutic approaches should be considered, regardless of the
      severity of anemia.

PMID- 24734281
TI  - Global state of sunscreens.
AB  - The use of sunscreen is embedded in a hierarchy of sun protection strategies
      consisting primarily of sun avoidance by seeking shade and covering up with
      clothing. Sunscreens are, however, important means of protection; thus,
      understanding how they work and knowing their limitations are crucial. This
      review explains the role of ultraviolet (UV) filters, emollients, emulsifier
      systems and other components in a sunscreen, as well as trends in formulations in
      Europe, North America, Latin America, and Asia Pacific. Furthermore, it explains
      how sunscreen performance in terms of sun protection factor, UVA protection, and
      other metrics can be simulated. The role of sensory characteristics in assessing
      and improving compliance is also discussed.In the final chapter, Facts and
      Fiction, five of the most common myths about sun exposure and sun protection by
      sunscreen are debunked.

PMID- 24734282
TI  - Influence of circulating levels of fibrinogen and perioperative coagulation
      parameters on predicting postoperative blood loss in cardiac surgery: a
      prospective observational study.
AB  - BACKGROUND: Fibrinogen, the major clotting protein in blood plasma, plays key
      roles in blood coagulation and thrombosis. In this prospective cohort study, we
      measured patient's fibrinogen levels and common coagulation parameters before and
      after cardiopulmonary bypass (CPB) and examined their relationships with
      postoperative blood loss. STUDY DESIGN: Patients undergoing cardiac surgery with
      CPB who did not have pre-existing coagulopathy were eligible. Standard blood and
      coagulation testing were performed before and after CPB. The association of these
      variables with postoperative blood loss (estimated blood loss from CPB) was
      assessed with Spearman's ranked correlation and multivariable linear regression
      models. RESULTS: Two hundred and fifty patients were enrolled in the study. The
      median blood loss was 780 mL (range 320-2340 mL). Variables independently
      associated with increasing blood loss were lower post-CPB platelet counts
      (p<0.001), lower postoperative fibrinogen levels (p<0.001), and larger percent
      decrease in fibrinogen levels (p<0.05). There was no correlation between
      preoperative fibrinogen levels and preoperative coagulation tests with
      postoperative bleeding. The only significant independent predictors of
      transfusion in a logistic regression model were postoperative fibrinogen
      concentration. CONCLUSION: Postoperative fibrinogen, the larger percent decrease
      in fibrinogen, and postoperative platelet levels are markers of bleeding and
      blood transfusion requirements after CPB than preoperative standard screening
      tests. Postoperative fibrinogen had the best predictive value of all tests of
      postoperative blood loss.

PMID- 24734283
TI  - Hybrid arch debranching and endograft repair in a patient with a ruptured
      thoracic aortic aneurysm.
AB  - Recent advances in hybrid techniques of aortic arch debranching allow for the
      repair of thoracic aortic arch aneurysm without requiring cardiopulmonary bypass
      or hypothermic circulatory arrest. We describe the repair of a ruptured proximal
      descending thoracic aortic aneurysm, using off-pump aortic arch debranching and
      antegrade transaortic deployment of a thoracic endograft in an elderly patient.

PMID- 24734284
TI  - Thromboelastography (TEG)-based algorithm reduces blood product utilization in
      patients undergoing VAD implant.
AB  - OBJECTIVES: Multiple blood products are often required during and after
      ventricular assist device (VAD) implants. Generally, transfusion therapy is
      empirically guided by conventional laboratory tests. In this study, we aimed to
      compare a thromboelastography (TEG)-based algorithm with a laboratory coagulation
      test-based algorithm with respect to blood product utilization in patients
      undergoing VAD implant. METHODS: From June 2010 to May 2012, a total of 39
      consecutive patients underwent VAD implantation. Patients undergoing VAD implant
      were retrospectively divided into two groups according to transfusion strategy.
      In the control group (n=20), the need for blood transfusion was based on
      clinician's discretion according to standard coagulation test results. In the TEG
      group (n=19), a strict protocol based on TEG parameters was followed for the
      usage of all perioperative blood products. Coagulation factors, TEG parameters,
      and blood transfusions were documented and compared between these two groups.
      RESULTS: There were no differences in demographic variables with the exception of
      a decreased CPB time in the TEG group (p=0.019). Prothrombin time (PT) (p<0.001)
      and international normalized ratio (INR) (p<0.001) in the postprotamine interval
      were significantly higher in the TEG group than in the control group. No
      significant difference was detected in any coagulation variable in the
      postoperative (ICU) period between the two groups. Platelet counts decreased in a
      linear fashion from baseline to the postoperative period in the two groups
      (p<0.001). Patients in the TEG group received significantly less fresh-frozen
      plasma in both the intraoperative (p=0.005) and postoperative (p=0.014) periods.
      Patients in the TEG group also received significantly less platelets both in the
      postoperative (p=0.03) period and in total amount (p=0.033). There was no
      difference in consumption of packed red blood cell units between the two groups.
      CONCLUSIONS: Our results show that the strict use of a TEG-guided algorithm
      significantly reduces the consumption of blood products in patients undergoing
      VAD implant

PMID- 24734285
TI  - Immunological comparison of allergen immunotherapy tablet treatment and
      subcutaneous immunotherapy against grass allergy.
AB  - BACKGROUND: IgE-mediated allergic rhinitis to grass pollen can successfully be
      treated with either allergen immunotherapy tablets (SLIT tablet) or SQ
      standardized subcutaneous immunotherapy (SCIT). The efficacy of these two
      treatment modalities for grass allergy is comparable, but the immunological
      mechanisms may differ. ClinicalTrials.gov ID: NCT01889875. OBJECTIVES: To compare
      the immunological changes induced by SQ-standardized SCIT and SLIT tablet.
      METHODS: We randomized 40 individuals with grass pollen rhinitis into groups
      receiving SCIT, SLIT tablet, or neither and followed them for 15 months with
      regular serum measurements of specific IgE, IgG4, IgE-blocking factor,
      facilitated antigen presentation (FAP), and basophil activation test (BAT). Nasal
      challenges were used to assess changes in nasal sensitivity. RESULTS: After 15
      months of treatment IgG4, IgE-blocking factor, FAP, and BAT values differed
      significantly in both SCIT and SLIT-tablet treatment groups when compared to the
      control group. Both SCIT and SLIT-tablet groups were significantly different from
      the control group after 1-3 months of treatment. In general, the changes induced
      by SCIT reached twice that of SLIT tablet, with the exception of specific IgE
      where SLIT tablet induced initial threefold increase compared with SCIT. A slight
      but significant increase in IgE and BAT after season was seen only in the control
      group. Significant differences between SCIT and SLIT tablet were observed early,
      but the differences diminished with the length of treatment, especially for FAP
      inhibition. CONCLUSIONS: Both SCIT and SLIT tablet induce significant changes in
      specific antibodies (IgE and IgG4) and competition assays (IgE-blocking factor,
      FAP, and BAT). Overall, SCIT induced larger (two- to threefold) changes than SLIT
      tablet, with the exception of FAP, where SLIT tablet showed a gradual increase
      ending at the same level as SCIT. Maximal change was generally reached after 3
      months' treatment.

PMID- 24734286
TI  - Author response.

PMID- 24734287
TI  - Cardiopulmonary exercise performance after total cavopulmonary connection with or
      without prior superior cavopulmonary connection.
AB  - OBJECTIVE: To compare cardiopulmonary exercise capacity of patients undergoing
      primary total cavopulmonary connection (TCPC) with those undergoing TCPC after a
      prior bidirectional Glenn (BDG). METHODS: Out of 42 patients in this study, 24
      had undergone primary TCPC while 18 had undergone staged TCPC. The peak oxygen
      consumption (O(2) peak), O(2) pulse, chronotropic index, and other exercise
      parameters were studied. RESULTS: There were no significant differences in O(2)
      peak (940 +/- 538 vs. 1010 +/- 417 mL/min, p=0.42) and O(2) pulse (5.76 +/- 3.52
      vs. 6.85 +/- 2.95) of patients undergoing staged TCPC versus primary TCPC,
      respectively; however, chronotropic index (0.43 +/- 0.23 vs. 0.30 +/- 017,
      p=0.047) was significantly different. Exercise tolerance was the same in
      fenestrated versus nonfenestrated TCPC groups and age at TCPC less than or more
      than 7 years. However, O(2) peak and O(2) pulse of patients with extracardiac
      TCPC was better than patients with lateral tunnel TCPC (p values 0.05, 0.04 and
      respectively). Some parameters of exercise tolerance of patients with antegrade
      pulmonary blood flow (APBF) interrupted at the time of BDG were better than those
      with APBF open. CONCLUSION: There were no differences in the exercise parameters
      of patients undergoing a staged versus a primary TCPC, fenestrated versus
      nonfenestrated TCPC, and age at surgery less than or more than 7 years. Exercise
      parameters were better in the extracardiac conduit group versus lateral tunnel
      TCPC groups. Patients who had a TCPC after prior interruption of APBF had better
      exercise parameters.

PMID- 24734288
TI  - Author response.

PMID- 24734289
TI  - Health gets greater attention in the 2014 Indian elections.

PMID- 24734290
TI  - Rethinking mental health care for young offenders.

PMID- 24734291
TI  - Childbirth in the UK: suffering and citizenship before the 1950s.

PMID- 24734292
TI  - Peramivir and laninamivir susceptibility of circulating influenza A and B
      viruses.
AB  - Influenza viruses collected from regions of Asia, Africa and Oceania between 2009
      and 2012 were tested for their susceptibility to two new neuraminidase
      inhibitors, peramivir and laninamivir. All viruses tested had normal laninamivir
      inhibition. However, 3.2% (19/599) of A(H1N1)pdm09 viruses had highly reduced
      peramivir inhibition (due to H275Y NA mutation) and <1% (6/1238) of influenza B
      viruses had reduced or highly reduced peramivir inhibition, with single
      occurrence of variants containing I221T, A245T, K360E, A395E, D432G and a
      combined G145R+Y142H mutation. These data demonstrate that despite an increase in
      H275Y variants in 2011, there was no marked change in the frequency of peramivir-
      or laninamivir-resistant variants following the market release of the drugs in
      Japan in 2010.

PMID- 24734293
TI  - Influenza H1N1pdm-specific maternal antibodies offer limited protection against
      wild-type virus replication and influence influenza vaccination in ferrets.
AB  - OBJECTIVE: The objective was to study passively acquired influenza H1N1 pandemic
      (H1N1pdm) maternal antibody kinetics and its impact on subsequent influenza
      infection and vaccination in ferrets during an outbreak of the H1N1pdm. DESIGN
      AND MAIN OUTCOME MEASURES: Infectivity of the H1N1pdm in the respiratory tract of
      ferrets was compared with the previous seasonal A/South Dakota/6/2007 (SD07,
      H1N1). Influenza-specific antibodies were quantitated and antibody-mediated
      protection against the homologous and heterologous H1N1 virus challenge infection
      was determined. RESULTS: H1N1pdm virus was approximately 10 times more infectious
      than SD07 in ferrets, replicated to higher viral titers in the upper respiratory
      tract and shed for a longer duration. Influenza-specific antibodies after natural
      infection persisted much longer in the circulation than passively acquired
      maternal antibodies. The protection conferred by the maternal antibodies was
      limited to the homologous virus strain and was ineffective against SD07 and H3N2
      virus. Serum antibodies from maternal transmission or passive transfer interfered
      with homologous vaccine strain-mediated antibody responses in the ferret. A
      booster immunization was required to elicit a high level of antibody.
      CONCLUSIONS: The findings support the rationale for a prime and boost
      immunization strategy in young children in whom maternal antibodies are present.

PMID- 24734294
TI  - Analysis of the acute-phase protein response in pigs to clinical and subclinical
      infection with H3N2 swine influenza virus.
AB  - BACKGROUND: Swine influenza (SI) is a contagious, important respiratory disease.
      Diagnosis of SI is based on the clinical signs, confirmed by the detection of
      viral RNA or specific antibodies. However, the infection is much more frequent
      than the disease. OBJECTIVES: The aim of study was to investigate the kinetics of
      acute-phase protein (APP) response during subclinical and clinical influenza in
      pigs. The utility of APP measurements in identification of infected animals was
      also evaluated. METHODS: Twenty-eight piglets were used. C-reactive protein
      (CRP), haptoglobin (Hp), serum amyloid A (SAA) and pig major acute-phase protein
      (Pig-MAP) concentrations in serum were measured using commercial ELISAs. RESULTS
      AND CONCLUSIONS: No relevant clinical signs were observed in intranasally
      infected pigs. In contrast, coughing, nasal discharge, and fever were observed in
      pigs infected intratracheally. All infected pigs exhibited specific antibodies in
      the serum at 10 dpi, and viral shedding was confirmed. The concentrations of CRP,
      Hp and SAA were significantly increased after infection. The level of Pig-MAP
      remained constant during subclinical and clinical infection. The concentrations
      of CRP, Hp and SAA were higher in pigs with clinical disease. Although not
      specific, strategic APP measurements may reveal ongoing clinical and subclinical
      infection. A close relationship between the magnitude of serum APP response with
      the severity of disease, providing an objective tool for validation the severity
      of infection. The maximum concentration of SAA in serum was closely correlated
      with lung score and makes this APP potential indicator for disease progress or
      estimation of treatment strategy.

PMID- 24734295
TI  - Variety of non-invasive continuous monitoring methodologies including electrical
      impedance tomography provides novel insights into the physiology of lung collapse
      and recruitment - case report of an anaesthetized horse.
AB  - INTRODUCTION: The use of alveolar recruitment maneuvers during general
      anaesthesia of horses is a potentially useful therapeutic option for the
      ventilatory management. While the routine application of recruitments would
      benefit from the availability of dedicated large animal ventilators their impact
      on ventilation and perfusion in the horse is not yet well documented nor
      completely understood. CASE HISTORY: A healthy 533 kg experimental horse
      underwent general anaesthesia in lateral recumbency. During intermittent positive
      pressure ventilation a stepwise alveolar recruitment maneuver was performed.
      MANAGEMENT: Anaesthesia was induced with ketamine and midazolam and maintained
      with isoflurane in oxygen using a large animal circle system. Mechanical
      ventilation was applied in pressure ventilation mode and an alveolar recruitment
      maneuver performed employing a sequence of ascending and descending positive end
      expiratory pressures. Next to the standard monitoring, which included spirometry,
      additionally three non-invasive monitoring techniques were used: electrical
      impedance tomography (EIT), volumetric capnography and respiratory ultrasonic
      plethysmography. The functional images continuously delivered by EIT initially
      showed markedly reduced ventilation in the dependent lung and allowed on-line
      monitoring of the dynamic changes in the distribution of ventilation during the
      recruitment maneuver. Furthermore, continuous monitoring of compliance, dead
      space fraction, tidal volumes and changes in end expiratory lung volume were
      possible without technical difficulties. FOLLOW: up The horse made an
      unremarkable recovery. CONCLUSION: The novel non-invasive monitoring technologies
      used in this study provided unprecedented insights into the physiology of lung
      collapse and recruitment. The synergic information of these techniques holds
      promise to be useful when developing and evaluating new ventilatory strategies in
      horses.

PMID- 24734296
TI  - Evaluation of analgesic and physiologic effects of epidural morphine administered
      at a thoracic or lumbar level in dogs undergoing thoracotomy.
AB  - OBJECTIVE: To evaluate the analgesic and physiological effects of epidural
      morphine administered at the sixth and seventh lumbar or the fifth and sixth
      thoracic vertebrae in dogs undergoing thoracotomy. STUDY DESIGN: Prospective,
      randomized, blinded trial. ANIMALS: Fourteen mixed-breed dogs, weighing 8.6 +/-
      1.4 kg. METHODS: The animals received acepromazine (0.1 mg kg-1) IM and
      anesthesia was induced with propofol (4 mg kg)-1 IV. The lumbosacral space was
      punctured and an epidural catheter was inserted up to the region between the
      sixth and seventh lumbar vertebrae (L, n = 6) or up to the fifth or sixth
      intercostal space (T, n = 8). The dogs were allowed to recover and after
      radiographic confirmation of correct catheter position, anesthesia was reinduced
      with propofol IV and maintained with 1.7% isoflurane. Following stabilization of
      monitored parameters, animals received morphine (0.1 mg kg-1) diluted in 0.9%
      NaCl to a final volume of 0.25 mL kg-1 via the epidural catheter, and after 40
      minutes, thoracotomy was initiated. Heart rate and rhythm, systolic, mean and
      diastolic arterial pressures, respiratory rate, arterial hemoglobin oxygen
      saturation, partial pressure of expired CO2 and body temperature were measured
      immediately before the epidural administration of morphine (0 minute) and every
      10 minutes during the anesthetic period. The Melbourne pain scale and the visual
      analog scale were used to assess postoperative pain. The evaluation began 3 hours
      after the epidural administration of morphine and occurred each hour until rescue
      analgesia. RESULTS: There were no important variations in the physiological
      parameters during the anesthetic period. The post-operative analgesic period
      differed between the groups, being longer in T (9.9 01.6 hours) compared with L
      (5.8 +/- 0.8 hours). CONCLUSIONS: The use of morphine, at a volume of 0.25 mL kg
      0.1, administered epidurally over the thoracic vertebrae provided longer lasting
      analgesia than when deposited over the lumbar vertebrae.

PMID- 24734297
TI  - Pity or peanuts? Oxytocin induces different neural responses to the same infant
      crying labeled as sick or bored.
AB  - The neuropeptide oxytocin plays an important role in mother-infant bonding.
      However, recent studies indicate that the effects of oxytocin on prosociality are
      dependent on perceived social context. Using functional magnetic resonance
      imaging, we examined differential effects of intranasally administered oxytocin
      on neural responding to 500 and 700 Hz crying that was indicated as emanating
      from a sick infant and 500 and 700 Hz crying emanating from a bored infant. We
      found that oxytocin significantly increased insula and inferior frontal gyrus
      responding to sick infant crying, but decreased activation in these brain regions
      during exposure to crying of an infant that was labeled as bored. In addition,
      oxytocin decreased amygdala responding to 500 Hz crying, but increased amygdala
      responding to 700 Hz crying. These findings indicate that labeling the same
      infant crying as 'sick' or as 'bored' drastically changes neural activity in
      response to intranasal oxytocin administration. Oxytocin increases empathic
      reactions to sick infants' crying, but lowers the perceived urgency of crying of
      an infant perceived as bored, thus flexibly adapting adult responses to infant
      crying labeled in various ways.

PMID- 24734298
TI  - Phononic crystal with adaptive connectivity.
AB  - The band structure of a phononic crystal can be controlled by tuning the
      mechanical stiffness of the links connecting its constituting elements. The first
      implementation of a phononic crystal with adaptive connectivity is obtained by
      using piezoelectric resonators as variable stiffness elements, and its wave
      propagation properties are experimentally characterized.

PMID- 24734300
TI  - Thin film metal nanocluster light-emitting devices.
AB  - Light-emitting devices that utilize thin films of metal nanoclusters as quantum
      emitters are presented. Implementing Ag as well as Au nanoclusters, the
      versatility of the approach is demonstrated, and it is shown that the
      electroluminescence measured from these devices is tunable by the choice of
      nanocluster. Ultimately, it is demonstrated that metal nanoclusters represent an
      additional option for future light-generating applications.

PMID- 24734299
TI  - Control of functional responses via reversible oxygen loss in La1-xSrxFeO3-delta
      films.
AB  - La0.3 Sr0.7 FeO3-delta films undergo dramatic changes in electronic and optical
      properties due to reversible oxygen loss induced by low-temperature heating. This
      mechanism to control the functional properties may serve as a platform for new
      devices or sensors in which external stimuli are used to dynamically control the
      composition of complex oxide heterostructures.

PMID- 24734301
TI  - High contrast fluorescence patterning in cyanostilbene-based crystalline thin
      films: crystallization-induced mass flow via a photo-triggered phase transition.
AB  - A facile and innovative method for the fabrication of highly fluorescent micro
      patterns is presented, which operates on the principle of phototriggered phase
      transition and physical mass migration in the crystalline film of a cyanostilbene
      type aggregation-induced enhanced emission (AIEE) molecule ((Z)-2,3-bis(3,4,5
      tris(dodecyloxy)phenyl) acrylonitrile) with liquid-crystalline (LC) mesomorphic
      behavior.

PMID- 24734302
TI  - Retraction: "Coaxial electrospinning of P(LLA-CL)/heparin biodegradable polymer
      nanofibers: potential vascular graft for substitution of femoral artery", by Zhai
      W, Qiu L-J, Mo X-M, Wang S, Xu Y-F, Peng B, Liu M, Huang J-H, Wang G-C and Zheng
      J-H.

PMID- 24734303
TI  - Retraction: 'IFATS collection: selenium induces improvement of stem cell
      behaviors in human adipose-tissue stromal cells via SAPK/JNK and stemness acting
      signals'.

PMID- 24734304
TI  - Pure endoscopic full-thickness resection with peritoneoscopy and omentectomy.
AB  - OBJECTIVE: To investigate surgical procedures for pure endoscopic full-thickness
      resection (EFTR) using a flexible endoscope and a prototype of a full thickness
      suturing device in animal experiments. METHODS: Six beagles were divided into two
      groups: sutured with over-the-scope-clip (OTSC group, n = 3) and with a prototype
      of the double-arm bar suturing system (DBSS group, n = 3). The peritoneoscopy,
      omentectomy and EFTR procedures were performed through the transgastric route. We
      examined the surgical procedures required to accomplish pure EFTR and survival
      rates of these dogs after EFTR. RESULTS: The duodenal balloon occlusion method
      maintained a sufficient endoscopic view during peritoneoscopy. Grooves of 10-mm
      wide were created around the tumor down to the third layer for treating all blood
      vessels and adding landmark for full-thickness resection lines. Using the muscle
      layer thin-cutting method, hyaluronic acid was locally injected into the muscle
      layer and fine incisions were made. Creating tiny perforations provided safe
      access to the abdominal cavity. Although it was difficult to suture the resected
      site safely in the OTSC group, the DBSS prototype was useful and reliable for
      closing there section sites with 3-0 absorbable thread. After EFTR there were no
      complications in the DBSS group and the dogs were in good health on POD 30,
      whereas in the OTSC group two dogs died due to dehiscence and gastric juice
      leaks. Postmortem examinations showed abscess around the suturing sites and two
      OTSC were detached from the suturing sites. CONCLUSIONS: Pure EFTR is feasible
      with DBSS when systematic methods are established. The high safety of full
      thickness resection suturing will permit their clinical application in the near
      future.

PMID- 24734305
TI  - Late onset of Crohn's disease in familial Mediterranean fever: the necessity of
      anti-TNF treatment.

PMID- 24734306
TI  - Total synthesis of hibarimicinone, a v-Src tyrosine kinase inhibitor possessing
      the pseudo-dimer structure of tetracycline.
AB  - The total synthesis of hibarimicinone, a potent v-Src tyrosine kinase inhibitor
      possessing thirteen stereogenic centers and an axial chirality, has been
      achieved. The key step to constructing the eight-ring skeleton was the double
      Michael-Dieckmann-type cyclization (Hauser annulation) using a thiolactone pseudo
      dimer. These synthetic studies indicated the efficiency of the thiolactone
      employed route to synthesize the multiply functionalized polycyclic compounds.
      The ABCD-ring moiety including the bridging ether was constructed by a strategy
      including oxidation of the C-ring hydroquinone and the subsequent transfer of the
      oxidation stage to the neighboring ring. The atropisomer of hibarimicinone was
      also synthesized to confirm the structure of the natural product.

PMID- 24734307
TI  - Liver transplantation for hepatocellular carcinoma: recent advances in China.
AB  - Orthotopic liver transplantation is currently the best treatment option for
      selected patients with hepatocellular carcinoma (HCC). From 1980 to 2011, 8874
      patients with HCC in China underwent liver transplantation. The organ donation
      classification criteria of China (China criteria), which are established by the
      Government of China, are divided into three parts: China criteria I, donation
      after brain death; China criteria II, donation after cardiac death and China
      criteria III, donation after dual brain-cardiac death. Data from the China Liver
      Transplant Registry(CLTR) System shows that patients within the Milan criteria
      have higher survival rates than those who are beyond these criteria. Based on
      CLTR data, altogether 416 patients received living-donor liver
      transplantation(LDLT) in China. Their 1-year and 3-year survival rates were
      significantly higher than those of the non-LDLT recipients. The most common early
      stage(<30 days after liver transplantation) complications include pleural
      effusion, diabetes, peritoneal effusion or abscess, postoperative infection,
      hypertension and intraperitoneal hemorrhage; while the most common late stage (>=
      30 days after liver transplantation) complications were diabetes, hypertension,
      biliary complications,postoperative infection, tacrolimus toxicity and chronic
      graft rejection. The incidence of vascular complication, which is the main reason
      for acute graft failure and re-transplantation, was 2.4%. Liver transplantation
      is an effective treatment for patients with HCC in China.

PMID- 24734308
TI  - Triazole-linked analogues of DNA and RNA ((TL)DNA and (TL)RNA): synthesis and
      functions.
AB  - Click chemistry has provided us with access to DNA and RNA analogues with non
      natural triazole internucleoside linkages. The bond periodicity of the
      oligonucleotides was designed to enforce duplex formation with natural congeners,
      and the non-cleavable linkages protect the oligomers against nuclease digestion.
      This account reviews the progress of the triazole-linked analogues over the past
      five years. Reinforced by their synthetic robustness, these analogues may find
      various utilities as tools for exploratory research.

PMID- 24734309
TI  - Asymmetric Mukaiyama aldol reactions using chiral diamine-coordinated Sn(II)
      triflate: development and application to natural product synthesis.
AB  - In 1989, the asymmetric Mukaiyama aldol reaction mediated by a Lewis acid
      consisting of a chiral diamine and Sn(II) triflate was reported. The asymmetric
      Mukaiyama aldol reaction is now widely used as a versatile tool for the
      construction of highly advanced, multifunctionalized molecules. In this Personal
      Account, the history of the development of this powerful methodology and the
      application of the asymmetric Mukaiyama aldol reaction in the synthesis of
      natural products are reviewed.

PMID- 24734310
TI  - Meta-methodology: conducting and reporting meta-analyses.

PMID- 24734311
TI  - Chocolate--guilty pleasure or healthy supplement?
AB  - Dark chocolate and other cocoa products are popular in the population as a whole,
      but their overall health benefit remains controversial. Observations from the
      Kuna Indian population have shown an impressive cardiovascular health benefit
      from cocoa. For various reasons, this benefit has not been as robust as in other
      populations. Additionally, several mechanisms have been proposed that might
      confer cocoa's possible health benefit, but no consensus has been reached on
      cocoa's physiologic role in promoting cardiovascular health. Flavanols, as well
      as theobromine, may contribute to enhancements in endothelial function and
      subsequent improvements in various contributors to cardiovascular disease (CVD)
      including hypertension, platelet aggregation and adhesion, insulin resistance,
      and hypercholesterolemia. While the benefits of cocoa may be altered at the
      various stages of growth, development, and production, it appears that for many
      people "healthy" dark chocolate may, indeed, provide a pleasurable role in CVD
      risk reduction. The objectives of this review are to discuss the associations of
      cocoa with decreased blood pressure and improved CVD risk, to describe the
      possible mechanisms for these potential benefits, and to highlight considerations
      for the use of cocoa as a dietary supplement.

PMID- 24734312
TI  - Pharmacokinetic interactions of the microsomal triglyceride transfer protein
      inhibitor, lomitapide, with drugs commonly used in the management of
      hypercholesterolemia.
AB  - STUDY OBJECTIVE: To characterize the effects of two doses (10 and 60 mg) of
      lomitapide-a microsomal triglyceride transfer protein inhibitor approved as
      adjunct treatment to lower low-density lipoprotein cholesterol levels in patients
      with homozygous familial hypercholesterolemia-on the pharmacokinetics of several
      lipid-lowering therapies: atorvastatin, simvastatin, rosuvastatin, fenofibrate,
      ezetimibe, and niacin. DESIGN: Two prospective open-label studies (study 1 and
      study 2). SETTING: Two clinical research units. SUBJECTS: A total of 130 healthy
      volunteers (114 subjects in study 1 and 16 subjects in study 2). INTERVENTION: In
      study 1, subjects were enrolled sequentially to one of the following eight open
      label treatment arms (probe drug + lomitapide): atorvastatin 20 mg + lomitapide
      10 mg, atorvastatin 20 mg + lomitapide 60 mg, simvastatin 20 mg + lomitapide 10
      mg, rosuvastatin 20 mg + lomitapide 10 mg, rosuvastatin 20 mg + lomitapide 60 mg,
      fenofibrate 145 mg + lomitapide 10 mg, ezetimibe 10 mg + lomitapide 10 mg, and
      extended-release niacin 1000 mg + lomitapide 10 mg. Study 2 consisted of the
      ninth treatment arm: simvastatin 40 mg + lomitapide 60 mg. Subjects received one
      dose of the probe drug on the morning of day 1. On days 2-7, subjects took their
      dose of lomitapide once/day in the morning. On day 8, subjects received one dose
      of lomitapide simultaneously with the same probe drug they took on day 1.
      Subjects returned 1 week later (day 15) for a final visit to check safety
      laboratory parameters. MEASUREMENTS AND MAIN RESULTS: A full pharmacokinetic
      profile was performed for the probe drug on day 1 and day 8 (after 7 days of
      dosing with lomitapide [i.e., at steady state]). Pharmacokinetic parameters were
      calculated from the plasma concentration-time data for each day by using
      noncompartmental methods. Analysis of variance was applied to the ln-transformed
      maximum concentration (Cmax) and area under the plasma concentration-time curve
      from time 0-t (AUC0-t) values, and ratios of the means were compared for day 8
      versus day 1. Lomitapide increased exposure to the statin medications. The
      percent least squares means ratios (LSMR%) (90% confidence intervals [CIs]) for
      AUC0-t of the statin medications with lomitapide at the 60 mg dose were as
      follows: 129 (115-144) for the sum of the active atorvastatin moieties, 168 (139
      203) for simvastatin acid, and 132 (112-157) for rosuvastatin. The LSMR% (90% CI)
      for Cmax was 138 (120-160) for the sum of the active atorvastatin moieties, 157
      (133-186) for simvastatin acid, and 104 (82-32) for rosuvastatin. The LSMRs were
      not appreciably altered for the other probe drugs. CONCLUSION: This study shows
      that lomitapide is a weak inhibitor of CYP3A4 and increased the exposure of
      statin medications. Careful monitoring of adverse events of CYP3A4-metabolized
      statins should be used when initiating therapy with lomitapide.

PMID- 24734313
TI  - A review of inhaled nitric oxide and aerosolized epoprostenol in acute lung
      injury or acute respiratory distress syndrome.
AB  - Acute respiratory distress syndrome (ARDS) and acute lung injury (ALI) are
      conditions associated with an estimated mortality of 40-50%. The use of inhaled
      vasodilators can help to improve oxygenation without hemodynamic effects. This
      article reviews relevant studies addressing the safety and efficacy of inhaled
      nitric oxide (iNO) and aerosolized epoprostenol (aEPO) in the treatment of life
      threatening hypoxemia associated with ARDS and ALI. In addition, the article also
      provides a practicable guide to the clinical application of these therapies. Nine
      prospective randomized controlled trials were included for iNO reporting on
      changes in oxygenation or clinical outcomes. Seven reports of aEPO were examined
      for changes in oxygenation. Based on currently available data, the use of either
      iNO or aEPO is safe to use in patients with ALI or ARDS to transiently improve
      oxygenation. No differences have been observed in survival, ventilator-free days,
      or attenuation in disease severity. Further studies with consistent end points
      using standard delivery devices and standard modes of mechanical ventilation are
      needed to determine the overall benefit with iNO or aEPO.

PMID- 24734314
TI  - Risk factors for exceeding the Milan criteria after successful  radiofrequency
      ablation in patients with early-stage hepatocellular  carcinoma.
AB  - Radiofrequency ablation (RFA) is an effective and safe noninvasive treatment for
      hepatocellular carcinoma (HCC) and may be useful as a bridging therapy in liver
      transplantation. The prognosis after liver transplantation for patients within
      the Milan criteria is excellent. This study was aimed at identifying risk factors
      associated with exceeding the Milan criteria after initial locally curative RFA
      therapy. Among 554 primary HCC patients, 323 with early-stage HCC after RFA were
      analyzed (mean age = 66 years). Two hundred forty-eight patients had hepatitis C
      virus, 33 patients had hepatitis B virus, and 41 patients had neither hepatitis B
      nor hepatitis C; 256, 67, and 0 patients were classified as Child-Pugh A, B, and
      C, respectively. The rates of cumulative overall survival and recurrence
      exceeding the Milan criteria were analyzed with Kaplan-Meier analysis, and
      factors associated with overall survival were determined with Cox proportional
      hazards analysis. The cumulative overall survival rates at 1, 3, 5, and 10 years
      were 96.2%, 84.4%, 69.9%, and 40.6% respectively, without liver transplantation.
      The cumulative rates of recurrence exceeding the Milan criteria at 1, 3, and 5
      years were 15.1%, 46.0%, and 61.1% respectively. An alpha-fetoprotein (AFP) level
      > 100 ng/mL and recurrence within 1 year after initial ablation were
      independently associated with earlier recurrence exceeding the Milan criteria and
      overall survival. The 3- and 5-year survival rates for patients with both risk
      factors were 33.5% and 22.6%, respectively, despite an early stage at initial
      ablation. In conclusion, a higher AFP level and HCC recurrence within 1 year of
      RFA are risk factors for exceeding the Milan criteria and for overall survival.
      Early liver transplantation or adjuvant therapy should be considered for patients
      with both risk factors.

PMID- 24734315
TI  - Nationwide survey of the outcomes of living donor liver transplantation for
      hepatoblastoma in Japan.
AB  - Recently, liver transplantation (LT) has been increasingly performed for
      unresectable hepatoblastoma (HB) with acceptable results. We conducted a national
      survey of cases undergoing living donor liver transplantation (LDLT) for HB to
      evaluate their outcomes. Thirty-nine patients (28 males and 11 females with a
      median age at LDLT of 3.6 years) who had undergone LDLT for HB by the end of 2009
      were enrolled in this study. The clinical data were collected from their medical
      records via a questionnaire survey in 2011 (median follow-up = 4.6 years).
      Thirteen patients (33.3%) had extrahepatic lesions before LDLT. Thirty-eight
      patients (97.4%) received chemotherapy, and 15 (38.5%) underwent hepatectomy
      before LDLT. Twenty-seven patients (69.2%) were alive without recurrence after
      LDLT, and 12 patients (30.8%) suffered from recurrence. The most common site of
      recurrence was the lung (9 cases), which was followed by the graft liver (6
      cases). The median interval from LDLT to recurrence was 5.5 months. Four of the 9
      cases (44.4%) with lung metastasis underwent surgical resection, and 3 were alive
      without any tumor recurrence. Eight patients died because of tumor recurrence.
      The multivariate landmark analysis revealed that the independent recurrence risk
      factors were a high alpha-fetoprotein (AFP) level at diagnosis [>= 500,000 ng/mL;
      hazard ratio (HR) = 7.86, P = 0.010], the presence of extrahepatic lesions before
      LDLT (HR = 3.82, P = 0.042), and a high AFP level at LDLT (>= 4000 ng/mL; HR =
      9.19, P = 0.036). The actuarial 3- and 5-year patient survival rates were 84.3%
      and 77.3%, respectively. In conclusion, with appropriate timing for scheduled LT,
      LDLT provides a valuable alternative treatment with excellent results for
      children with HB.

PMID- 24734317
TI  - Is your system ready for population health management?
AB  - Health care organizations will need to migrate to population health management
      sooner rather than later in response to statutory and regulatory pressures coming
      from the federal government.

PMID- 24734318
TI  - Coexistence of lobular granulomatous mastitis and ductal carcinoma: a fortuitous
      association?
AB  - A 77-year-old female patient with a medical history significant for hypertension
      and epilepsy presented with right breast pain of 6-months duration. Examination
      revealed a hard sub-areola tender mass with irregular borders associated with
      mild right nipple retraction. Mammography showed a 2.2 x 2.4 cm stellate mass of
      the right breast. Ultrasound-guided core biopsies of the tumour were performed.
      Pathological examination revealed a grade II infiltrating ductal carcinoma. The
      patient underwent right radical mastectomy with homolateral axillary
      lymphadenectomy. Histological examination of the surgical specimen revealed grade
      II infiltrating ductal carcinoma concomitant with granulomatous lobular mastitis.
      To the best of our knowledge, the coexistence of granulomatous lobular mastitis
      and ductal carcinoma has been described only twice in the English language
      literature. The theory that chronic inflammation leads to cancer is well
      documented. Whether our patient had developed cancer from granulomatous lobular
      mastitis or otherwise is a matter of debate until more cases are encountered and
      more research is done in the area of breast cancer pathogenesis with regards to
      it arising from granulomatous lobular mastitis.

PMID- 24734316
TI  - Tetraspanin 3c requirement for pigment cell interactions and boundary formation
      in zebrafish adult pigment stripes.
AB  - Skin pigment pattern formation in zebrafish requires pigment-cell autonomous
      interactions between melanophores and xanthophores, yet the molecular bases for
      these interactions remain largely unknown. Here, we examined the dali mutant that
      exhibits stripes in which melanophores are intermingled abnormally with
      xanthophores. By in vitro cell culture, we found that melanophores of dali
      mutants have a defect in motility and that interactions between melanophores and
      xanthophores are defective as well. Positional cloning and rescue identified dali
      as tetraspanin 3c (tspan3c), encoding a transmembrane scaffolding protein
      expressed by melanophores and xanthophores. We further showed that dali mutant
      Tspan3c expressed in HeLa cell exhibits a defect in N-glycosylation and is
      retained inappropriately in the endoplasmic reticulum. Our results are the first
      to identify roles for a tetraspanin superfamily protein in skin pigment pattern
      formation and suggest new mechanisms for the establishment and maintenance of
      zebrafish stripe boundaries.

PMID- 24734319
TI  - [Multiple sclerosis and occupational exposures: results of an explorative study].
AB  - OBJECTIVES: The aim of the study is to explore possible relationships between
      occupational exposures and Multiple Sclerosis (MS), whose etiology is not well
      defined yet. To date, only few literature data are available on this subject.
      METHODS: We carried out a case-control study, where cases were MS patients
      included in the MS Register of the Province of Pavia, Northern Italy, and
      controls, 1:4 matched by sex and age (5 years classes), were randomly selected
      from the National Health Service population files. The occupational histories
      were obtained from Italian Institute for Social Security (INPS) archives by
      automatic linkage using Italian Occupational Cancer Monitoring (OCCAM) method
      that estimates the risk of specific occupational cancers, by geographic area and
      industrial sector. OR adjusted for sex and age and corresponding 90% confidence
      intervals were used to estimate the association between exposure and disease.
      RESULTS: We included in the study 227 MS patients (130 (57.3%) female, 97 (42.7%)
      male) and 907 controls (514 (56.7%) female, 393 (43.3%) male). Our results
      suggest an increased risk for men in mechanical manufacturing industry (OR 1.71,
      90% CI 1.03-2.85) and agriculture (OR 2.47, 90% CI 1.03-5.91). Women show an
      increased risk in mechanical manufacturing industry (OR 2.05, 90% CI 1.22-3.45),
      agriculture (OR 2.57, 90% CI 1.09-6.09) and leather/shoe industry (OR 2.34, 90%
      CI 1.06-5.20). CONCLUSIONS: Our preliminary findings indicate that solvent
      exposures could be related to the risk of MS, as both shoe/leather workers and
      mechanical manufacturing industry workers are exposed to organic solvents.
      Interestingly, a major risk of MS was also found among workers engaged in
      agriculture, suggesting a role of pesticides, whose neurotoxic effect is well
      known.

PMID- 24734320
TI  - [Presenteeism and workers' health: effects of mediation on psycho-physical stress
      in a longitudinal study].
AB  - The present work aims to investigate the phenomenon of presenteeism, a construct
      still little studied, especially in Italy, in its medical, psychological, social
      and economic implications. In the first part we propose a review of the
      international literature, and of the meanings, causes and consequences of the
      phenomenon on individual and organizational health. In the second part, we
      present a study which involved, for a period of about a year, 326 workers of a
      company in the engineering industry. This study is, in this writers' knowledge,
      the first survey--characterized by a longitudinal design and a multi-method
      approach, both not very present also in the international literature--carried out
      in our country on the phenomenon of presenteeism. The survey examines the
      mediating role of presenteeism in the relationship between specific risk factors
      of work context and content--career growth, conflict with colleagues, social
      rewards--and the psycho-physical strain. The risk factors were detected through a
      self-report instrument at the beginning of the year. The workers, at the end of
      the same year, were subjected to a healthcare surveillance visit in which the
      competent physician evaluated the psycho-physical strain. The hypothesized
      relations have been tested by estimating a structural equation model with
      observed variables. What emerged was a negative association between social
      rewards and presenteeism and a positive relation between conflict with colleagues
      and presenteeism. Instead, no association between growth and presenteeism
      emerged. Presenteeism, in turn, predicts psycho-physical strain. Overall,
      presenteeism mediates the relationship between social rewards and strain, as well
      as between interpersonal conflict and strain, but not between growth and strain.
      This work is characterized by some innovative aspects compared to previous
      studies conducted on the subject, both in theory and methodology. From a
      theoretical point of view the hypothesized model aims to capture specific risk
      factors of the process leading to the formation of work stress, through the role
      of presenteeism. From a methodological point of view the adoption of a
      longitudinal and multi-method research design allows a better understanding of
      the relationships between the variables investigated, often limited by the
      exclusive use of self-report instruments in cross-sectional designs. Finally, the
      possible interventions aimed at preventing presenteeism and minimizing its
      negative consequences on health are discussed.

PMID- 24734321
TI  - Excessive daytime sleepiness works together with other sleep disorders in
      determining sleepiness-related events in shift workers.
AB  - BACKGROUND: Shift-workers may experience sleep disturbances more frequently than
      day-workers. Interactions between obstructive sleep apnea (OSA), shift-work and
      other factors promoting sleepiness have never been studied. The present study was
      designed to assess the prevalence of excessive daytime sleepiness (EDS), high
      risk for OSA (HR) and insomnia in shift-workers and day-workers and to evaluate
      their mutual effects on the risk of home-to-work commuting car accidents or
      episodes of falling asleep during work. METHODS: Workers (153 shift-workers, 85
      day-workers) were evaluated for the presence of sleep disorders including HR and
      EDS. The relationships between sleepiness-related events, shift-work and sleep
      disorders were investigated by path analysis. RESULTS: Forty-nine subjects had
      HR. EDS was more frequent in shift-workers than in day-workers (16.3% vs. 5.9%, P
      = 0.01) and in workers with HR (28.6% vs. 8.4%, P < 0.001) or insomnia (35.7% vs.
      9.5%, P < 0.001). Path analysis support the evidence that EDS was directly linked
      to shift-work, HR and insomnia. Car accidents or falling asleep at work were
      directly associated with EDS and shift-work, and indirectly (via EDS) with HR and
      insomnia. CONCLUSIONS: Development of EDS in shift-workers is not only due to
      work schedule, but also to the presence of sleep disorders. OSA and insomnia co
      promote falling asleep during work and sleepiness-related car accidents.

PMID- 24734322
TI  - [Occupational stress in municipal police officers: contribution to the Italian
      adaptation of a questionnaire for the assessment of the operational and
      organizational stressors].
AB  - INTRODUCTION: The study of occupational stress in police has received growing
      interest because of the potential negative effects that it may produce both on an
      individual and on an organizational level. The aim of the present research is to
      give a first contribution to the Italian adaptation of two questionnaires used in
      order to assess operational and organizational stressors in police: the
      Operational Police Stress Questionnaire (PSQ-Op) and the Organizational Police
      Stress Questionnaire (PSQ-Org). METHODS; The PSQ-Op-It and the PSQ-Org-It have
      been administered to all the municipal police officers serving the population of
      a small town in Northern Italy (N = 88). An explorative factor analysis has been
      carried out to verify the internal structure; in order to assess the concurrent
      validity, correlations with psycho-physical malaise (GHQ-12) and burnout (MBI-GS)
      have been calculated. RESULTS: The factor analysis (rotation method oblimin)
      confirmed the original structure of the two questionnaires: two factors,
      corresponding to organizational and operational stressors, have been extracted.
      The Cronbach's alphas of the two questionnaires, 0.95 and 0.94 respectively, have
      pointed out good internal consistency. The two instruments are related to the
      subscales of the GHQ-12 and the MBI-GS, with the exception of the professional
      inefficacy dimension. CONCLUSIONS: The PSQ-Org-It and the PSQ-Op-It have shown
      good psychometric properties, so they could be used in order to assess police
      specific stressors. Nevertheless we suggest to deepen the obtained results by
      confirmative factor analyses to carry out through the administration of the
      instrument to more numerous samples, in different and more structured urban
      contexts.

PMID- 24734324
TI  - [Job demands and work-family conflict in a health care staff. The role of work
      shifts].
AB  - INTRODUCTION: Work-family conflict (wfc), that originates from an incompatibility
      between the job and the family demands, is a very relevant topic in health care
      context, as suggested by NEXT study. Work overload and schedule organization are
      dimensions that can affect wfc, and particularly, studies indicate work shifts as
      one of its main determinants, as they limit the work-family balance and represent
      one of the prime risk factors for workers' health. The aim of this study was to
      detect the role of some job demands (both general and specific) and of schedule
      organization in determining the wfc experience, with particular attention to work
      shifts. METHODS: Respondents to our questionnaire are 207 nurses of a north
      Italian public health organization. They are mostly women (92.8%) and their
      average age is 42. RESULTS: Data analysis shows that wfc is mostly influenced by
      work shifts, but also by work overload, cognitive load and by on-call
      availability. Staff working on shifts and on-call availability perceive a higher
      wfc than their colleagues without work shifts and on-call availability.
      CONCLUSIONS: The central role of work shifts in determining wfc suggests the need
      to act on schedule organization and on training programs for supervisors and
      workers.

PMID- 24734323
TI  - [Biological risk among health workers].
AB  - INTRODUCTION: In health care the contact with body fluids, such as saliva or
      blood is frequent. The aim of our study was to analyze whether the exposure to
      biological risks in health care, in particular exposure to HBV and HCV, could
      cause alterations of some liver parameters. MATERIALS AND METHODS: Our study
      analyzes of 254 health care workers of a big hospital in Rome. The subjects
      exposed to biological risks were divided into two groups, one exposed to a high
      biological risk and the other one exposed to a low biological risk, according to
      individual duties and/or the departments where they carry out their work. We
      checked the markers for hepatitis B and C in order to highlight a possible
      infection, the possible vaccine coverage and the control of the antibody titer by
      previous infection. We measured the values of transaminases, GGT, alkaline
      phosphatase, total bilirubin and fractional proteinaemia total and
      electrophoresis. RESULTS: In health care workers exposed to high risk the average
      values of transaminases, total protein, alkaline phosphatase, gamma GT, total
      bilirubin were not significant compared to the some values formed in workers
      exposed to low risk (p > 0.05). Subjects positive for hepatitis B and C were 4%
      in the group of workers exposed to high risk (class 1) while in the group of
      workers exposed to low risk (class 2) the percentage of exposed individuals was
      0.01% for the hepatitis B and 2.6% for hepatitis C. DISCUSSION AND CONCLUSIONS:
      We found a small numbers of positive cases of hepatitis B and C in people exposed
      to biological agents. We did not find alterations of the average values of
      transaminases, total protein, alkaline phosphatase, gamma GT, total bilirubin and
      albumin in positive cases, so that we can say that the proper use of personal
      protective equipment, training and information of workers and the observance of
      universal precautions are effective in protecting workers.

PMID- 24734325
TI  - [Update on electrical safety of equipment used in surgery and interventional
      medicine].
AB  - Update on electrical safety of medical equipment used in Surgery and
      Interventional Medicine. Expanding on the theme of relevant operating safety has
      become extremely topical as a result of the broad diffusion of electro-medical
      equipment in medical and surgical practice. This aspect is related to the
      technical features of the equipment, to regulations to be observed inside medical
      facilities, to the correct use of the equipment. The article suggests a setting
      up of the problem, outlining the physiological and pathological effects of
      electric currents on the human body and indicating regulations in force as to
      electric safety of electro-medical equipment and of facilities used for medical
      and surgical purposes, and examines common clinical situations at electrical
      risk.

PMID- 24734326
TI  - [Neuropsychological evaluation and psychological intervention on patients with
      Parkinson's disease in physical rehabilitation].
AB  - OBJECTIVE: Parkinson's Disease (PD) is characterized by a wide range of motor and
      non-motor symptoms. In the last years the evaluation of cognitive functioning,
      emotional aspects and health status of PD patients has became ever-growing
      important. METHODS: In this article a neuropsychological and psychological
      assessment model, by means of tests and interviews, and a clinical approach to
      the narrative themes are described. Areas of clinical investigation: cognitive
      processing, emotional acceptance and behavioural adaptation to the disease,
      motivation to rehabilitation treatment, expectations regarding functional
      recovery, adherence, social and family perceived support, mood, awareness of
      possible cognitive deficits. Tests assessment (based on specific cognitive
      deficits related to PD): MMSE, FAB, TMTA-B, Phonological verbal fluency test,
      Stroop test, Geriatric Depression Scale (GDS) or Beck Depression Inventory- BDI
      II and Parkinson's Disease Questionnaire-8 (PDQ-8). The psychological approach,
      which is part of an interdisciplinary rehabilitative intervention, is based on
      Cognitive Behavioural Therapy and it is focused on disease management even in the
      absence, sometimes, of a significant general emotional status modification and it
      is aimed at improving patient's adaptability, self-management and empowerment. In
      order to describe the model, the clinical and test data of two PD patients are
      illustrated. CONCLUSIONS: The added value of this psychological approach lies in
      the clinical data integration of the test evaluation, the narrative aspects and
      the information mediated by the inter-professional team. This model allows a
      deeper and more personalized identification of the patient's subjective
      adjustment process according to his/her personal needs and resources.

PMID- 24734327
TI  - [Address by the rector of the Pomeranian Medical University in Szczecin
      inaugurating the academic year of 2012/2013].

PMID- 24734328
TI  - Ectrodactyly-ectodermal dysplasia-cleft syndrome (EEC syndrome) with a
      developmental delay caused by R304W mutation in the tp63 gene.
AB  - Ectrodactyly-ectodermal dysplasia-cleft syndrome (EEC) results from a
      simultaneous developmental abnor-caused by mutations of the tp63 gene. Five
      mutations: 204, 227, 279, 280, and 304 account for most cases of this syndrome. A
      case with R304W mutation, characterized by the presence of all major
      (ectrodactyly, ectodermal dysplasia, cleft lip and palate) and two minor
      (lacrimal duct obstruction, developmental delay) clinical symptoms of the
      syndrome is presented. This severe case improves the existing knowledge
      concerning the genotype-phenotype correlations in EEC syndrome.

PMID- 24734329
TI  - [A coexistence of the Dupuytren's disease and malignant neoplasms: a review].
AB  - Dupuytren's disease is classified as a benign superficial fibromatosis, in which
      excessive proliferation of myofibroblats and formation of nodules and chords
      occurs, followed by development of finger contractures. The similarities between
      Dupuytren's disease and neoplasms were shown at molecular and clinical grounds.
      The objective of the study was to review of the literature investigating possible
      relationship between occurrence of Dupuytren's disease and malignancies. Review
      of the few available papers shows (1) statistically significantly increased
      malignant neoplasm mortality among men with advanced Dupuytren's disease,
      comparing to reference population and men with early stage of the disease, (2)
      statistically significantly increased malignant neoplasm morbidity, mainly
      related to smoking and alcohol consumption among patients (men and women)
      operated on for Dupuytren's disease and (3) increased sarcoma of the bone and
      soft tissue morbidity in patients 5 years after operation for Dupuytren's
      disease. Some genetical studies show also altered expression of the
      dehydrogenases ALDH2 and DHDH genes in patients with Dupuytren's disease and with
      digestive tract malignancies related to alcohol abuse.

PMID- 24734330
TI  - [Elevated blood pressure as cardiovascular risk factor].
AB  - Cardiovascular diseases for decades have been and still are the main and current
      health problem of the Polish society and there are many reasons for these
      diseases. Hypertension is one of the major risk factors for developing
      cardiovascular disease. The factors significantly increasing risk the of
      cardiovascular disease are in addition to high blood pressure, smoking (also
      passive), high blood fats (cholesterol and its HDL, LDL fractions as well as
      triglyceride levels, obesity, lack of exercise, diabetes and hereditary features.
      Other important factors which play an important role are external factors such as
      e.g. environmental pollution, lifestyle, stress. Prediction of cardiovascular
      disease should start from the evaluation of the fetal period because low birth
      weight may be a risk of coronary heart disease, hypertension, obesity or diabetes
      in adulthood. The authors of the referred tests showed that the level of blood
      pressure observed during childhood is closely associated with the level of blood
      pressure in adults and is also dependent on the body weight. Since the issue of
      the effects of high pressure on the cardiovascular system is inherent in the
      issue of the metabolic syndrome, it should be mentioned also that another
      causative factor may be an irregularity in the removal of urine from the body and
      the amount of insulin. The control of hypertension is a complex problem, at least
      in view of the wide range of adverse factors affecting the human body:
      hypertension is often either a constituent of other lesions. Therefore, it is
      difficult to treat high blood pressure in the strict sense; more often it is a
      combination therapy based on pharmacology caused for other reasons.

PMID- 24734331
TI  - [Biochemical risk factors for cardiovascular disease in children].
AB  - The problem of finding the biochemical markers for determining cardiovascular
      risk is complex, difficult and multidisciplinary. Even in a simple biochemical
      blood test the number of possible variables significant for indicating the
      negative changes in the cardiovascular system is high. The image created from a
      variety of factors is fuzzy, inconclusive and sometimes difficult to define and
      explain. Contemporary cardiology uses fixed operative levels and the presence of
      biochemical factors as the basis for patient diagnosis. Even a thorough and multi
      biochemical analysis can not give conclusive results. Many precautions are needed
      in using the results of biochemical analysis. Ambiguous results may be
      misleading, disrupt the analytical process, or suggest probable, but not
      necessarily the correct, solutions. This biochemical analysis presented points to
      the most important prognostic factors and biochemical information used in the
      cardiological treatment of children and adolescents.

PMID- 24734332
TI  - [Depression in children and adolescents -symptoms, etiology, therapy].
AB  - Early onset depression, regarding its high prevalence and debilitating effects on
      development, is considered to be one of the major mental illness in children and
      adolescents. Most commonly is recurrent and continues in adulthood. Factors
      determining vulnerability to depression can be grouped into following categories:
      genetics, familial environment, personal characteristics and severe stress. Main
      risk factors include: being a female, family history of depression, subclinical
      symptoms, negative cognitive style, negative life events. Common symptoms of
      depression can be different in children and teens than they are in adults. Often
      occur with atypical features. The diagnosis might be problematic as it often
      relays on the observation of children's dysfunctions. Therefore treatment of
      major depression in children and adolescents is considered difficult. It is
      important to estimate all the features that underlie the symptoms, their
      persistence, and then implement proper therapy.

PMID- 24734333
TI  - [Monitoring of hospital infections in cardiac surgery ward].
AB  - INTRODUCTION: The development of techniques applied in cardiac surgery changed
      the profile of operated patients. Patients with small lesions within the
      cardiovascular system are treated using invasive cardiology. The occurrence of
      infections is directly related to the type of surgery and the implanted material.
      Many hospitals, even in the developed countries, contend with hospital
      infections, which are the source of serious clinical and economic problems.
      Paradoxically, problems associated with hospital infections have grown worse
      along with advances in medicine and the implementation of new invasive diagnostic
      methods. Cardiac surgery wards are specialist units, where infections among
      patients are quite common. Hospital infections are dangerous for patients' health
      and even life. They also contribute to the failure of therapy. Therefore, the
      awareness of infections and their reasons, which may help to control and
      eliminate this problem, is so important. The aim of this study was an annual
      forward-looking analysis of hospital infections in the cardiac surgery ward,
      which included: patients' profiles, clinical forms of infections, aetiological
      factors and infection risk factors in patients with various types of cardiac
      surgical procedures. MATERIAL AND METHODS: This forward-looking study involved
      all patients hospitalised in the Cardiac Surgery Clinic, the Pomeranian Medical
      University of Szczecin in the period 1.01-31.12.2008. The total number of
      participants was 1127, including 804 (71.3%) men and 323 (28.7%) women. analysis
      of procedures used in cardiac surgery wards so far and the offer of optimal
      prevention measures. Each patient had his/her own infection registration card.
      The material for microbiological tests was taken in accordance with a routine
      procedure once a week or in cases of suspected infections. CONCLUSIONS: 1.
      Infections were detected in 7.2% of patients. 2. Death rates among patients with
      infections was higher in women than in men (46.2% vs 33.3%). 3. The most common
      clinical forms of infection were pneumonia (44.4%), sepsis (42.0%) and surgical
      site infection (33.3%), however every infected patient had 1-4 clinical forms. 4.
      The most common aetiological factors of infection, irrespective of a clinical
      form, were Gram-negative rods with the prevalence of Enterobacter cloacae and
      Pseudomonas aeruginosa. 5. Patient-related infection risk factors included
      overweight and womens' age > 72, while a statistically significant increase in
      the incidence of infections was found in patients who had not received anti
      thrombosis treatment. 6. Infection risk factors associated with treatment and
      specificity of the cardiac surgery ward were mainly: artificial ventilation > 24
      h, the necessity for reoperation, a blood transfusion, pressor administration,
      treatment complications, as well as not using extracorporeal circulation and
      surgical site drainage. 7. Risk factors related to treatment complications
      included mainly: circulatory problems, renal insufficiency, respiratory
      insufficiency, low cardiac output syndrome and ischaemic cerebral stroke. 8.
      There were no correlations between infections and the course of surgery, the type
      of a prosthesis (mechanical/biological) or catheterization of vessels and the
      bladder. 9. The presented results enable the analysis of procedures used in
      cardiac surgery wards so far and the offer of optimal prevention measures.

PMID- 24734334
TI  - [Replantation and reconstruction vs terminalization in the treatment of
      amputation of the digits].
AB  - MATERIAL AND METHODS: This study records the outcomes of the treatment of 21
      patients, 19 men and two women, who sustained an amputation of the total of 35
      digits (27 fingers and eight thumbs). Eleven patients received replantation or
      reconstruction maintaining the length of the digit, whereas ten had their digits
      terminalized. RESULTS: The results were assessed at a mean of 5 years after
      injury. Patients with finger stumps had stronger grip than those with replanted
      digits (72% vs 48% of strength of the healthy hand). Hand function as assessed by
      quickDASH score (29 vs 33), quality of life as assessed by SF-36 score (63 vs 67)
      and number of patients experiencing cold sensitivity (7 vs 7) were similar in
      both groups. Patients after terminalization returned to work significantly
      earlier than those after replantation or reconstruction (6 vs 12 months).
      CONCLUSIONS: These results show that - considering function of the hand -
      replantation or advanced reconstruction offers the patient less benefit than
      simple terminalization.

PMID- 24734335
TI  - [Patients functioning after surgical treatment for Perthes disease].
AB  - INTRODUCTION: Perthes disease appears in children and affects hip joints. The
      proximal head of the femur is damaged, which results in deformation of the
      femoral ball and loss of its spherical shape. Instant diagnosis and introduction
      of treatment is crucial for maintaining the femoral head in the hip socket, which
      facilitates recovery to its spherical shape. To assess the quality of life of
      patients who have undergone surgical treatment. The factors examined were: state
      of functioning and occurrence of pain in affected hip joint. MATERIAL AND
      METHODS: 61 participants underwent the examination. The duration and type of
      disease were established on the basis of a radiogram. The patients were treated
      with varus derotation osteotomy in the 2 and 3 degree of the Reinberg scale. A
      Modified Oxford Hip Score was used to assess the patients' quality of life.
      RESULTS: Subjective assessment of the quality of life after recovering from the
      disease was regarded as very good and good. CONCLUSION: According to the
      patients' own evaluation the disease and the treatment did not affect their
      everyday life.

PMID- 24734336
TI  - [A rare case of exposure to natural psychoactive substances, and difficulties
      with medicolegal assessment].
AB  - An unusual case of exposure to natural psychoactive substances deriving from
      Datura stramonium (jimsonweed, thorn-apple) is presented in this article. It may
      be of interest in this case that a hallucinogenic substance was intentionally
      administered by a third party. An initial assessment in this criminal case was
      questionable, and resulted from a lack of consideration of toxicological exposure
      and its possible aftermath. The above-mentioned case demonstrates the necessity
      of considering all toxicological aspects of the case, even though initial
      findings seemed to indicate something else.

PMID- 24734337
TI  - [Mesenteric infarction of the small bowel in the course of portal vein thrombosis
      - a case report].
AB  - Portal vein thrombosis is a rare entity, usually concomitant with hepatic
      cirrhosis and malignancies. Spontaneous disease occurs very rarely, and it
      presents with venous small bowel mesenteric infarction, causing intestinal
      ischaemia extremely rarely. We present a patient who was operated on because of
      symptoms and signs of "acute abdomen" and in whom segmental ischaemia of the
      small bowel and mesenteric thrombosis were found intraoperatively. The correct
      diagnosis, mesenteric infarction of the small bowel in the course of portal vein
      thrombosis, was made after performing an abdominal computer tomography scan a
      week after surgery. The course of the treatment, complications, and data from the
      literature are presented about this very rare condition, which may constitute a
      difficult diagnostic problem for a surgeon.

PMID- 24734338
TI  - Influence of semipermanent cement application used in immediately loaded, implant
      supported restorations on crestal bone resorption.
AB  - INTRODUCTION: The paper presents clinical-radiological research on the impact of
      the new semi-cement luting agent in the immediately loaded implant-supported
      restoration on alveolar ridge resorption. MATERIAL AND METHODS: 25 patients with
      a partially edentulous alveolar ridge in the anterior section of the maxilla or
      mandible were included in the study. The implants were inserted with the
      application of traditional burs or with a Piezosurgery device supplied by
      Mectron. Taking into account the method of implant bed preparation, the
      scientific material was divided into two groups. The implants were loaded
      immediately with single crown restorations cemented with the Implantlink semi
      cement application. The following indices were taken into consideration: pocket
      depth around implant calculated at four measuring points, marginal alveolar bone
      loss measured using radio-visiography, the 3-degree Wachtel scale of healing of
      the soft tissue. In addition, the presence and possible width or height of any
      recession around the implants was measured. The success of the implant treatment
      was assessed according to the Albrektsson success criteria. The research results
      were subjected to statistical analysis. RESULTS: The results of our study
      revealed no influence of the Implant-link semi cement on the crestal bone level,
      regardless of the bone bed preparation technique.

PMID- 24734339
TI  - [Analysis of variation of orbital openings in contemporary skulls].
AB  - INTRODUCTION: The size and symmetry of the eye-socket have puzzled many medical
      and biological scientists. The orbit is a very complicated skull part because of
      the great number of bones involved in its structure, and its specific
      physiological function. The aim of our study was to estimate variations in the
      shape, size and position of the orbital openings in contemporary human skulls by
      using computer software. MATERIAL AND METHODS: The material consisted of 80 male
      human skulls of the European population from the beginning of the 20th century. X
      ray photographs were taken in the P-A projection, then the images were scanned
      and calibrated by means of MicroStation 95 Academic Edition software. Tools for
      measuring the vector elements were used to assess measurements: n-mf, mf-ml, mf
      ek, spa--sbk and the area of the orbital opening. The orbital index and the index
      of morphological asymmetry were assessed. Michalski's tables were used to
      establish orbit features. The statistical analysis was performed using the
      Statistica computer software package. RESULTS AND CONCLUSIONS: Measurements of
      the eye--socket position in relation to the mid-line were significantly more
      frequently larger on the left-hand side, which means a more lateral position of
      orbits on that side. The measurements of breadth, height and area were more
      frequently larger on the right side. The asymmetry index was significant for
      orbit width. The majority of the examined orbits were classified as hypsikonch,
      according to the orbital index. According to Michalski's scale, the dominant size
      data described orbital openings in the European population from the West
      Pomeranian region. The awareness of variability in this area is necessary for the
      correct interpretation of patients' examination results, reconstruction planning,
      in forensic medicine, and anthropology.

PMID- 24734340
TI  - [Variation in the course of human veins based on the anatomical and morphometric
      research].
AB  - INTRODUCTION: The cardiac veins have inspired numerous generations of
      researchers. From anatomists and pathologists to cardiologists and cardiac
      surgeons, the issue of the structure of heart and cardiovascular disorders- in
      spite of enormous progress of medicine - have not been completely discovered so
      far. MATERIAL AND METHODS: The material of the research comes from the collection
      of the Chair and Department of Normal and Clinical Anatomy of the Pomeranian
      Medical University and it includes 102 human hearts, of which 59 male and 43
      female ones, aged from 12 and 70. Both coronary veins and arteries of the tested
      hearts were filled with the epoxy resin, which allowed for thorough exposing and
      differentiating between the venous vessels and the arterial vessels. The aim of
      this study was to assessing the interrelationships between the dimensions of the
      heart, the size of the coronary sinus, the length of the cardiac veins and a sex.
      Also determined the frequency and variability of cardiac veins run in the
      material, as well as the correlation between the topography of the course of the
      great cardiac vein, the middle cardiac vein, the branches of the left and right
      coronary arteries and the cardiac size and a gender. The measurements of the
      heart and the veins were made with the use of a pair of spherical compasses, an
      electronic caliper, a goniometer and a planimeter. RESULTS: It was found that the
      size of the male heart is statistically significantly greater than the female
      one. The dimensions of the heart correlated positively with the diameter and the
      length of the coronary sinus (CS) and the length of the great cardiac vein (GCV),
      the middle cardiac vein (MCV) and the small cardiac vein (SCV). The length of the
      CS positively correlated with its diameter and the length of the veins draining
      into it. The veins which were not always present in the tested material included:
      the SCV, the right marginal vein (RMV), the oblique vein of the left atrium
      (OVLA), the left marginal vein (LMV). It was found that the length of the GCV and
      the MCV in males were statistically significantly greater. The length of the MCV
      positively correlated with the length of the GCV, the SCV, the OVLA, the
      posterior vein of the left ventricle (PVLV), the LMV. The anastomoses between the
      GCV and the MCV were more often found in males and it was a statistically
      significant difference. It was found that there is a positive correlation between
      the venous arch connecting the GCV and the MCV and the length of the GCV. The
      anastomoses between the PVLV and the MCV and the LMV did not correlated with a
      sex, but it statistically significantly correlated with the length of the right
      and left PVLV and with the length of the MCV.

PMID- 24734341
TI  - [Anthropometric, densitometric and histometric investigations into the
      development of the femoral bone in human foetuses].
AB  - INTRODUCTION: The purpose of this study was the estimation of foetal femoral bone
      development, based on anthropometric, densitometric and histometric examination.
      MATERIAL AND METHODS: The study was done on 68 foetuses (31 female and 37 male)
      of various foetal ages (16-31 weeks of gestation). The specimens, ranging 16-31
      weeks of gestation, were divided into 3 groups for better statistical analysis.
      After the left and right limb were removed from specimens each femoral bone was
      radiographed using a Microfocus 401 bone X-ray apparatus. Radiographs were
      digitized with an analogue camera and an A/D converter for transfer to a
      computer. Four measurements were taken for each bone: the total length of the
      shaft; the breadth of the proximal epiphysis; the breadth of the central part of
      the shaft; and the breadth of the distal epiphysis. After anthropometric research
      densitometric research was started within which BMC and BMD measurements were
      taken by a DPX-L osteodensitometer, Lunar, Wisconsin, USA, for tiny osseous
      structures. Mean values for results were calculated, and their correlation with
      the age and sex of the examined foetuses was described. The bones examined were
      cleared of soft tissues, and afterwards histological specimens were taken from
      the proximal epiphysis, the central part of the shaft, and the distal epiphysis
      for histometric study. The obtained histological images were saved on the
      computer, and processed using a special image analyser. During the experiment the
      surface area and circumference oftrabeculae of bone were calculated. The obtained
      values were used for estimating histometric indicators that describe the osseous
      structure of the proximal epiphysis, the central part of the shaft, and the
      distal epiphysis. RESULTS: Results of this research from certain parts of the
      femoral bone were described for the right and left limbs in correlation with the
      foetuses' age and sex. It has been stated that arbitrary diameters of foetal
      femoral bone are strongly and positively correlated with the total length of the
      femoral bone, CRL and the age of the examined foetuses. Anthropometric analysis
      of foetal femoral bones in the early stage of development do not indicate
      lateralization features. The mineral content of femoral bones (BMC) indicates a
      characteristic, positive correlation with foetal age, but the mineral density of
      foetal femoral bones (BMD) does not correlate with its development. The density
      of the femoral bone in human foetuses increases with age in all bone's parts and
      histometric parameters of foetal femoral bones show variability in terms of sex
      at an early stage of intrauterine development. Based on the given anthropometric
      densitometric and histometric data the occurrence of foetal dimorphism features
      has been analyzed in randomly chosen foetal groups. The cluster analysis and
      analysis of many other parameters of developing femoral bone revealed features of
      sexual dimorphism in selected groups of human foetuses.

PMID- 24734342
TI  - [Watsu: a modern method in physiotherapy, body regeneration, and sports].
AB  - Progress in existing methods of physiotherapy and body regeneration and
      introduction of new methods has made it possible to precisely select the
      techniques according to patient needs. The modern therapist is capable of
      improving the physical and mental condition of the patient. Watsu helps the
      therapist eliminate symptoms from the locomotor system and reach the psychic
      sphere at the same time.

PMID- 24734343
TI  - The health behaviour of people in late adulthood -sociodemographic correlations
      and differences between social environments.
AB  - PURPOSE: The increasing number of elderly people living in society draws
      attention to the problem of health promotion and health education. The present
      day problem is prevention in late adulthood and - as a consequence - keeping
      healthy. In this study the relationships between the individual categories of the
      health behaviour of the aged and those social-demographic variables which
      characterize this research group were analysed. The following were taken into
      consideration: age, sex, education of the test subjects, and whether or not the
      test subjects belong to a University of the Third Age (UTW) circle, or whether or
      not the test subjects belong to a social welfare centre circle (DPS). MATERIAL
      AND METHODS: A total of 199 persons, over 60 years old, living in Bydgoszcz and
      Torun were tested. The questionnaire method was used in the study. The
      questionnaire used was the Health Behaviour Inventory by Z. Juczynski. Spearman's
      non-parametric test and the Mann-Whitney U Test were used for statistical
      analysis. RESULTS: Among the four categories of health behaviour and its general
      intensity only the positive psychological attitude score has a relationship that
      is of statistical significance to belonging to a DPS or UTW group. Education was
      seen to be the variable that most often correlates with health behaviour (the
      behaviour's general indicator and positive psychological attitude). The higher
      the level of education, the greater the intensity of this behaviour. The sex
      variable is of marginal significance. The p-value is less than 0.05 (p < 0.05)
      only for eating habits. Age differentiates the scores pertaining to sleeping and
      recreational habits, along with physical activity. The younger group scored
      lower, on average. CONCLUSIONS: Health behaviour during the period of late
      adulthood is influenced by both belonging to DPS or UTW groups and
      sociodemographic characteristics. There was no evidence of a dominating variable
      which significantly differentiates the individual health behaviour categories.
      Programmes promoting healthy lifestyle should be addressed to a wide group of
      recipients. Variables such as age, sex and level of education are not as
      significant for health behaviours as predicted. That is the reason to refer to
      other sociodemographic parameters.

PMID- 24734344
TI  - [Overdosing of popular medicines available without a prescription, a new trend
      among teenagers].
AB  - INTRODUCTION: For last several years popularity of substances which improve
      concentration or/and cause hallucinations has considerably increased. There is a
      conviction that most frequent addictions among teenagers are cigarettes, alcohol
      or drugs of abuse. A very dangerous phenomenon has been ignored, becoming more
      common among scholars and students - usage of medicines available without
      doctor's prescription (over the counter drugs - OTC). Popularity and fame of
      these specifics comes from side effects observed especially when overdosed.
      MATERIAL AND METHODS: In years 2007-2012 in Clinical Toxicology Laboratory of
      Medical Pomeranian University 4304 toxicological analyses was conducted with
      specified direction on drugs analysis (39% of all analyses made in that period).
      In some cases, especially of young people, a doctor ordering the analysis pointed
      as possible cause of intoxication "recreational usage" of OTC drugs. Those
      suspicions were confirmed by toxicological examinations. CONCLUSIONS: It seems
      that dominating character feature of people who abuse psychoactive substances is
      emotional immaturity. Maturation process can be impaired or completely inhibited
      by abusing psychoactive substances. This is processes are considered which
      enhance immaturity of person's personality - so called defense mechanisms.

PMID- 24734345
TI  - [Incidence of trauma in young football players aged 15-19].
AB  - It is obvious that sports have beneficial effects on health, but they often pose
      a certain risk to health. Recent studies point to the growing number of injuries
      and accidents among players practicing football. Players are injured during a
      match (65.68%) more often than during training (34.31%). The most common injuries
      include damage to the lower extremities (97%) including: bruising (56.70%),
      muscle and ligament injuries (17%), tearing muscles and ligaments (13.40%) and
      fractures (13%). A forced break in training activity contributes to the weakening
      of the player's performance, which is why one of the main goals of rehabilitation
      is to restore it as soon as possible. This paper is devoted to the
      characteristics of injuries among players practicing football. The survey
      comprised 102 athletes of both sexes, practicing in Polish football clubs, at
      various levels of competition, e.g. junior team of players aged under 17 years
      representing Poland.

PMID- 24734346
TI  - [Characteristics of miscarriage and women's rights after pregnancy loss].
AB  - The term "miscarriage" refers to the end of pregnancy before the 22nd week of
      gestation, or taking into account the criterion of foetal weight (less than 500
      g). Approximately 15-20% of recognized pregnancies and miscarriage involve
      spontaneous expulsion of the blastocyst from the uterine cavity. This constitutes
      about 80% of miscarriages in the first 12 weeks of gestation. The literature
      lists a number of factors which cause the loss of pregnancies. The most
      frequently cited causes of abortion are: genetic, anatomical, immunological and
      hormonal factors, and infections. A large number of miscarriages remain
      unexplained (idiopathic miscarriages). Clinical signs of miscarriage include
      bleeding and pain. Bleeding or spotting is the earliest sign of miscarriage. Data
      from the patient's history, physical examination, ultrasound examination and
      tests for hCG level can enable diagnosis of bleeding in early pregnancy, help to
      assess the degree of risk, and implement an appropriate treatment regimen and
      care for pregnant women adapted to their needs. Loss of pregnancy is an
      interdisciplinary problem involving obstetrics, epidemiology, public health,
      psychology, and other specialities. The role of medical personnel in the care of
      women after the loss of a child, regardless of the week and therapeutic
      procedures, as well as for giving adequate information regarding the rights of
      women after pregnancy loss. The obligation to inform women of their rights
      concerns medical staff, and it is important to promote knowledge in this field
      among doctors, nurses and midwives who care for women after miscarriage.

PMID- 24734347
TI  - [Neuroethics: new quality of medical ethics?].
AB  - During the last decade there has been a striking growth in interest in ethical
      issues arising from the development of neurosciences. It was as late as 2002 that
      the new discipline, called neuroethics, started. It was intended to be a new area
      of interdisciplinary discourse on moral dilemmas connected with recent advances
      in, broadly understood, neurosciences. Ten years after its launch neuroethics
      possesses a distinct body of knowledge and an institutional basis for its further
      development. As a very young discipline, however, neuroethics is still in a state
      offlux. Two essential theoretical concepts of how this discipline is to be built
      on are emerging. Both are discussed in this article. According to the first of
      them (i.e. ethics of neurosciences), neuroethics is basically understood as a sub
      -discipline of bioethics. Although there are some reasons for distinguishing
      several branches or sub-disciplines of bioethics (genethics, neuroethics,
      nanoethics, etc.), there are sound arguments against such a tendency for the
      proliferation of biomedical ethics. The second approach to neuroethics
      (neuroscience of ethics), which aims at studying neuronal correlates of the well
      known ethical concepts (e.g. free-will, moral responsibility, etc.), seems to be
      much more promising. Neuroethics understood in this way (and only in this way)
      can be considered as a truly new opportunity for collaboration between
      neuroscientists and ethicists.

PMID- 24734348
TI  - [The development of treatment in the Birstonas health resort up to 1939 and the
      physicians of Birstonas in the 19th and first half of the 20th century].
AB  - First of all, the history and development of Birstonas, a health resort by the
      river Neman, near Vilnius, first mentioned in 1382, are recounted in detail. The
      value of this health resort was determined by a mild climate and salt springs.
      Information on Birstonas by Wladyslaw Syrokomla (1823-1862), the Polish poet, and
      Zygmunt Gloger (1845-1910), the Polish ethnographer, archaeologist and historian
      are well known. The indications and contraindications in many diseases, and the
      effects of treatment in this health resort are described. Finally, the
      opportunities for recreation and the attractions in this charming health resort
      are presented. Attention was paid to the leading role of Poles in the development
      of this health resort now in Lithuania. The biographies of several physicians
      practicing in Birstonas: Jan Sokolowski, Aleksander T.W. Korewa, Anicety Renier,
      Stanislaw K. Wikszemski, Benedykt Bilifiski, Erminio Andriolli, Roman Przybylski
      and Pawel A. Sawicki are presented. Their biographies, professional achievements
      and work in Birstonas are depicted in detail.

PMID- 24734349
TI  - [The development of treatment in a health resort in Niemirow until the end of the
      second republic].
AB  - The history ofNiemirow, a health resort on the south-eastern borderland of Poland
      is recounted in full particulars first of all. A mild climate, charming regions,
      natural stuffs (sulphuric-alkaline salt springs and therapeutic mud) formed the
      status of this health resort. The indications and contraindications in many
      diseases and effects of treatment in a health resort are described. The bats in
      Niemirow and fixtures are presented widely. The chances of recreation and
      attractions in this health resort are presented finally.

PMID- 24734350
TI  - History of urology in Iwow (Lemberg, Lviv). the impact of political changes on
      progress in urology and medicine.
AB  - Innovations in diagnostic techniques due to the introduction of endoscopy, and
      the development in X-ray technology were fundamental in lessening dependence on
      surgery, and for urology to be recognised as a new discipline. Afterwards,
      endoscopic surgery came to the fore. Urology in Lemberg, The aim of the study is
      to present the development of urology in Lemberg as an independent speciality,
      and its separation from surgery. Well-known Lemberg surgeons who were interested
      in surgery of the genitourinary system are discussed. The beginning of urology
      and its development within the framework of surgical departments, and as an
      independent facility in the interwar period is described. The fate of the Polish
      department of urology during the interwar period and the World War II is also
      presented. The development of Ukrainian urology after the World War II is also
      described. Extensive research was undertaken to collect the literature and
      documents in Polish and German archives and libraries in order to prepare this
      study. The author also presents the leading Ukrainian urologists who contributed
      from the post war period to the last 22 years of free Ukraine (from December
      1991), and discusses the development of modern urology in Lviv today.

PMID- 24734351
TI  - Methotrexate pharmacology in leukaemia cells -letter to the editor.

PMID- 24734352
TI  - [Present and future perspectives for the rapid molecular diagnosis of TB and MDR
      TB].
AB  - Tuberculosis is still one of the diseases with a major medical and social impact,
      and in terms of early diagnosis (which would imply a fair treatment and
      established at the time), difficulties related to the delay bacilli isolation in
      culture, decreased susceptibility testing methods to antituberculosis drugs, lack
      of methods for differentiation of M. Tuberculosis complex germs of non-TB
      Mycobacteria, may have important clinical implications. Traditional testing of
      anti-TB drug susceptibility on solid Lowenstein-Jensen medium (gold standard) or
      liquid media can only be performed using grown samples. Determining the time it
      takes up to 42 days on solid media and 12 days for liquid media. For MDR/XDR TB
      cases itis absolutely essential to reduce the detection time. In these cases
      rapid diagnostic methods prove their usefulness. Automatic testing in liquid
      medium, molecular hybridization methods are currently recommended by the current
      WHO guidelines. Rapid diagnosis of MDR-TBis extremely useful for the early
      establishment of an effective treatment tailored more accurately on the spectrum
      of sensitivity of the resistant strain (thus reducing the risk of developing
      additional resistance to other drugs) and control the spread of these strains.
      Genetic diagnostic methods, approved and recommended by the WHO, can reduce the
      time of diagnosis of TB case and, importantly, the case of MDR-TB. They do not
      replace the current standard diagnostic methods and resistance profile, but
      complete them in selected cases.

PMID- 24734353
TI  - Interstitial lung diseases: an observational study in patients admitted in
      "Marius Nasta" Institute of Pulmonology Bucharest, Romania, in 2011.
AB  - Interstitial lung diseases (lLD) are a large group of rare diseases, with
      difficult diagnosis and management. Very little is known about prevalence,
      diagnosis and management of ILDs in Romania. This study aims to gather
      information on how ILDs are diagnosed and managed in Romania, focusing on a
      tertiary hospital with expertise and equipment needed for accurate diagnosis. We
      analyzed retrospectively the files of patients admitted with ILD in 2011 in
      "Marius Nasta" Institute of Pulmonology Bucharest. There were 178 eligible
      patient files with ILDs and 186 sarcoidosis cases. The ILD diagnosis were: 41
      cases idiopathic pulmonary fibrosis (IPF), collagen disease associated ILD (29
      cases), hypersensitivity pneumonia (19 cases), alveolar proteinosis (9 cases),
      cryptogenic organizing pneumonia (9 cases), undefined ILD (46 cases), other (25
      cases). The investigations used for the diagnosis were: chest X-ray (100%),
      spirometry (157pts, 88.21%), diffusion capacity (127 pts, 71.43%, broncho
      alveolar lavage (92 pts, 51.69%), CT scan (141 pts, 79.22%), lung biopsy (26 pts,
      14.6%), similar to other European centers, but fewer lung biopsies are performed.
      There is need for a prospective registration of ILD cases in a national registry,
      for creating local guidelines for diagnosis of ILDs, to improve the suspicion of
      ILD and referring of patients to specialized centers. Diagnosis can be improved
      by a multidisciplinary approach of each case, involving the clinician, the
      radiologist, the pathologist and the thoracic surgeon.

PMID- 24734354
TI  - Inhaled steroids reduce apnea-hypopnea index in overlap syndrome.
AB  - BACKGROUND: Obstructive sleep apnea (OSA) and chronic obstructive pulmonary
      disease (COPD) are two of the most common chronic respiratory disorders. Co
      existence of both conditions, referred as overlap syndrome (OLS), is associated
      with substantially high rates of mortality and morbidity. The present study aimed
      to evaluate the effect of inhaled corticosteroids (ICS) on apnea-hypopnea index
      (AHI), an indicator for diagnosis and identifying the severity of OSA, in overlap
      syndrome. METHODS: We conducted a clinical trial on 60 patients diagnosed with
      overlap syndrome by employing overnight polysomnography before and after
      receiving ICS. Tstudent test and Mann-Whitney test were applied to analyze the
      gathered data including age, AHI, nocturnal oxygen desaturation index and SaO2,
      (saturated arterial oxygen), daytime (pressure of arterial carbon dioxide) PaCO,
      level, forced expiratory volume in one second (FEV1), body mass index (BMI), and
      waist and neck circumferences. RESULTS: By 3-month ICS administration, this study
      demonstrated significant reduction of mean AHI and nocturnal oxygen desaturation
      index along with remarkable improvement of FEV1, diurnal PaCO2, level and
      nocturnal SaO2, (P< 0.05). Meanwhile, BMI and waist and neck circumferences
      measurement showed no noticeable changes. CONCLUSION: As we have not found any
      literature demonstrating, this is the first study which has evaluated the effect
      of ICS on AHI in overlap syndrome. Because of a remarkable improvement in
      obstructive sleep apneas, this study suggests that ICS might be beneficial in
      treatment of overlap syndrome.

PMID- 24734355
TI  - The impact of 0.5% chlorhexidine oral decontamination on the prevalence of
      colonization and respiratory tract infection in mechanically ventilated patients.
      Preliminary study.
AB  - AIMS: To determine the effect of Chlorhexidine (CHX) 0.5% oral decontamination on
      the incidence of colonization/infection of lower respiratory tract in critically
      ill mechanically ventilated patients. METHODS: The study was conducted in the
      multidisciplinary ICU. 30 patients, mechanically ventilated for at least 48
      hours, were included. The oral care was performed every 6 hours (6 h CHX group)
      or 12 hours (12 h CHX group). Tracheal samples were collected every day and the
      mucosal plaque score (MPS) was also assessed. RESULTS: The MPS score averages
      were between 3.8 and 6 in the 6 hours CHX group and between 3.6 and 5 in the 12
      hours CHX group. There was no positive association between MPS score and
      frequency of CHX decontamination (p= 0.898). For 60% of patients in 6 h CHX group
      and for 40% of patients in 12 h CHX group, colonization did not develop until
      leaving the study. No significant difference were found between groups with
      respect to frequency of colonization based on its time of onset (p= 0.523). There
      is a relationship between the isolation of MRSA and CHX oral decontamination at
      12 hours (<phi c =0.392, p=0.032). CONCLUSIONS: In our preliminary study, no
      signifficant differences were found between 6 or 12 hour CHX oral decontamination
      with respect to MPS score and colonization. However, MRSA is vulnerable to 6
      hours CHX decontamination. Larger sample size studies are required to determine
      the efficacy of CHX in the prevention of colonization or respiratory tract
      infections in mechanically ventilated patients.

PMID- 24734356
TI  - Modified minimally invasive pectus repair in children, adolescents and adults: an
      analysis of 262 patients.
AB  - In order to achieve safe and successful funnel chest treatment even in older
      patients and reduce postoperative complications, we modified the procedure of
      minimally invasive pectus repair using the single-piece pectus bar (PSI Hofer
      Medical, Austria) with no metal abrasion. The features of modified minimally
      invasive funnel chest correction (MMIPR) are the following: (a) additional
      subxiphoidal incision, (b) anterior mediastinal-mediastinoscopic mobilization,
      (c) mediastinoscopy, (d) elevation of the funnel during pectus bar placement, and
      (e) fixation of the implant ends in a latissimus dorsi muscle bag, below the
      anterior margin of the muscle. In older funnel chest patients with a stiff
      thorax, a curved sternum, marked asymmetry or a mixed pigeon/funnel chest, the
      minimally invasive correction method has to be supplemented by additional
      surgical measures (MEMIPR) such as partial sternotomy (23%), slit-rib chondrotomy
      under thoracoscopic guidance (Rokitansky method; 48%), rib resection (5%), and
      occasionally rib osteotomy. In 8 patients with residual minor deformities we
      administered an ultrasound-guided Macrolane injection (5 to 20 cc). 262 patients
      (mean age: 17.7+/-7 years) were eligible for analysis. The large majority of them
      underwent MIPR between the age of 14 and 20 years; 6 patients were older than 40
      years. The pectus bar implant was left in the chest for a period of 1.4 to 6.5
      years. Modified minimally invasive pectus repair (MMIPR) was performed in 121
      patients (mean age: 15.2+/-5 years). The majority of patients received one pectus
      bar; 13.2% received two bars. Modified extended minimally invasive pectus repair
      (MEMIPR) was performed in 141 patients (mean age: 22.5+/-8 years); two pectus
      bars were used in 58.1% of cases. We observed no bar dislocation. Minimal bar
      movements were noted in 1.6% (MEMIPR) and 4.9% (MMIPR) of cases. With the MEMIPR
      technique, subcutaneous hematoma was observed in 4.1% of patients. No re
      thoracotomy was required in the 262 patients who underwent MMIPR or MEMIPR. After
      a mean period of 3.4 years the implants were removed surgically in 103 patients;
      recurrences were observed 0.9%. Our procedures of MMIPR and MEMIPR with a single
      piece pectus bar permitted safe and successful surgery in patients who required
      complex funnel chest correction.

PMID- 24734357
TI  - [Microcalorimetry -- a new method for bacterial characterisation].
AB  - The microcalorimetry is a method used for recording of the heat produced by a
      thermodinamic system in a scale of micronanojouls. One of the domains in which
      this method is used is the one called bacterial microcalorimetry, which studies
      the heat generated by the bacterial populations. The process of bacterial growth
      can be monitored in real time by the recording a graph of the generated power
      over time. The modern isothermal microcalorimeters allow the detection of a
      signal variation of only one microwatt. The estimated generated power of a
      bacteria is approximately 1-4pW thus only a small number of bacteria is necessary
      for the experiments. Recent studies in the field of bacterial microcalorimetry
      have demonstrated that, in standard conditions, this method can be reproductible
      and can be used to detect and characterize bacterial growth (through the study of
      the microcalorimetric growth curve particular to a bacterial species which is
      called a microcalorimetric fingerprint) and offers the new information in regards
      to bacterial metabolism. Also, microcalorimetry can offer information about
      bacterial interaction with different factors in the medium (for example,
      antibioticsubstances, in which case an antibiogram is obtained in 4-5 hours). In
      conclusion, we can say that microcalorimetry is a reproducible method, which
      offers an interesting perspective on bacterial characterization, with great
      scientific potential, and there are sufficient arguments to continue studies in
      this field.

PMID- 24734358
TI  - [Role of surgery in small cell lung cancer].
AB  - Role of surgery in small cell lung cancer Small-cell lung cancer (SCLC) is a very
      aggressive neuroendocrine carcinoma that accounts for approximately 10-15% of all
      lung cancer cases. This histological subtype is a distinct entity with biological
      and oncological features differing from non-small cell lung cancer (NSCLC).
      Standard treatment is performed using systemic chemotherapy, and surgery in
      association with chemotherapy and radiotherapy may be indicated for a minor
      proportion of cases with limited disease. Since the results after surgical
      intervention in patients with very early disease are comparable to those for
      NSCLC, careful staging is required, especially in terms of nodal involvement- use
      of PET-CT EUS, EBUS and/ or mediastinoscopy is recommended. However, only two
      randomized control studies have examined the efficacy of surgery in SCLC, and
      both yielded negative results and are out of date. We review here several studies
      concerning surgery for SCLC and discuss the results from a practical standpoint.

PMID- 24734359
TI  - [The importance of determining the prevalence of COPD].
AB  - The chronic obstructive pulmonary disease (COPD) is a common, preventable and
      partially treatable disease. COPD often remains undiagnosed, until it reaches
      advanced stages and significantly affects thepatient's quality of life. In the
      European Union the direct costs of COPD represent 56% (38.6 billion euro
      annually) of the direct costs of pulmonary diseases in the health budget. We
      analyzed a series of studies and we observed that the prevalence values vary
      between 6.5% (Lu Ming, China), 8.13% (Mihaltan Florin, Romania), 10.1% (the BOLD
      study), 17.4% (Peder Fabricius, Denmark). In Romania, the COPD prevalence is
      partially known, a recent study that evaluated the COPD prevalence on national
      level revealing a value of 8.13% in the population with an age over 40 years.
      Most of the studies include a selected population (smokers, age over 40, with or
      without symptoms). Establishing the prevalence of this disease as precise as
      possible becomes a necessity, even if this is pretty difficult to accomplish; the
      methods used in many studies on this subject are not uniform, thus the obtained
      results cannot be compared and correctly evaluated. Getting to know the
      prevalence of this disease as exact as possible is a difficult challenge, but
      extremely necessary for evaluating the seriousness of the phenomenon and getting
      to know the prevention and fighting measures. It is necessary to establish a
      methodology that has maximum effectiveness in identifying the COPD cases not only
      at an age over 40, but at lower ages as well, as it was proven that the disease
      can appear, even if more rarely, at ages below 40 as well. This article is part
      of a study which intends to try to determine a national wide applicable
      methodology.

PMID- 24734360
TI  - [Sexuality and eroticism face to face].

PMID- 24734361
TI  - [Public health and sexuality].
AB  - The paper questions the legitimacy and relevance of a potential emergence of any
      public health policies relating to sexology, as they exist for most of the major
      medical issues. It discusses the two major areas of intervention of sexology
      namely problems related to access to pleasure on the one hand, violence, abuse
      and other sexual perversions on the other hand. The legitimacy and relevance of
      public health policy to prevent the latter, i.e. sexual violence cannot be
      questioned. However, interventions to promote erotic skills are beyond the role
      and responsibility of the State but can be assigned to the civil society,
      especially community associations engaged in culture, solidarity and the
      promotion of social links in general.

PMID- 24734362
TI  - [Interdependance between somatic symptoms, sleep and dreams].
AB  - Even in an established illness, somatic complains can hide other emotional
      inquiries. The therapist, always with a kind attitude, can ask more about
      patient's sexual life. This can be use of having a better idea of patient's life
      and problems. Talking about dreams can also be useful: it gives new and
      surprising elements about patient's personality and helps to progress on
      healing's way.

PMID- 24734363
TI  - [Treatement of sex offenders: limits and possibilities].
AB  - Sexual offending is a matter of public concern and of interest to caregivers
      because of the consequences to the victims. Though there is a high prevalence of
      paraphilias among sexual aggressors, there is no strict link between aggressive
      sexual behavior and psychiatric disorders. Several typologies of sex offenders,
      based on personality and motivation, have been described. According to several
      studies, recidivism risk, for all known typologies of sex offenders, is estimated
      to be around 15% at 5 years. The use of standardized scales improves the
      reliability of the risk assessment. Psychotherapy, with or without a
      pharmacological treatment, forms the basis of the psychiatric treatment of these
      patients. Serotoninergic selective reuptake inhibitors, antiandrogens and GnRH
      analogues are the main drugs that are used.

PMID- 24734364
TI  - [Sex therapy for sexual dysfunctions].
AB  - Sex therapy, a specialized form of psychotherapy for sexual dysfunctions,
      combines the three main therapeutic approaches, cognitive-behavioral, family and
      psychodynamic in an integrated approach. The treatment emphasis is first placed
      on the sexual symptom and then, if necessary, on understanding the underlying
      intrapsychic and interpersonal aspects of the disorder. In addition to work on
      the body and fantasies, sex therapy has integrated in recent years a number of
      innovative approaches: combination therapies, internet therapy, pain therapy and
      mindfulness. Sexual disorders can be difficult to treat. It is, therefore,
      important to take into account the role of biological, psychological, relational
      and cultural factors.

PMID- 24734365
TI  - [Psychotherapy of sexual perversions: is it possible?].
AB  - Different psychotherapeutic interventions in order to cure paraphilic
      symptomatology appeared until now rather disappointing. We propose a new modality
      focusing especially on some particular aspects, for example the relationship
      between pleasure and pain and between excitation and inhibition.

PMID- 24734366
TI  - [Complications of body piercing].
AB  - The trend of body piercing has grown in popularity in the past decade within the
      general population and especially among young adults. Complications of body
      piercing include local inflammation and infections, but severe complications are
      also possible and largely underestimated. People are usually not aware of the
      risks before making a piercing, and their medical history, medication and
      comorbidities are largely neglected by the people who realise the piercing. This
      article presents a review of the complications that a primary care physician may
      observe, for a patient who wishes to make a piercing, or presents complications
      due to the implementation of such a device.

PMID- 24734367
TI  - [The "second life" of rifampicin].
AB  - Despite it was initially used and was restricted mainly for the treatment of
      tuberculosis, rifampicin gained in past years interest for the treatment of
      infections associated with prosthetic devices. Rifampicin has an excellent tissue
      penetration and a unique activity on bacteria in biofilms growing on the surface
      of prosthetic devices. The rapid emergence of resistance in bacteria constitutes
      the Achilles' heel and therefore rifampicin should be used with caution. This
      review addresses the mode of action of rifampicin and describes possible pitfalls
      of its use.

PMID- 24734368
TI  - [Found dead (6 hours too late) at the Cochin hospital emergency department].

PMID- 24734369
TI  - [Thrown out of home].

PMID- 24734370
TI  - [Do you dare enter the Grand Cabinet of Medical Curiosities?].

PMID- 24734371
TI  - [Let's not return to the era before antibiotics - phagotherapy (2)].

PMID- 24734372
TI  - [Fine particle air pollution].

PMID- 24734373
TI  - [Specially trained personnel can save lives while waiting for the ambulance].

PMID- 24734374
TI  - [Information in health care: Students' rights to access medical records should be
      regulated].

PMID- 24734375
TI  - [ E-cigarettes are a poor alternative to quitting smoking. Health risks and
      dependence is poorly researched].

PMID- 24734376
TI  - [Economic cycles and public health: The aftermath of the Iceland banking crisis].

PMID- 24734377
TI  - [Injuries in gallbladder surgery--again and again. Event analyses indicate that
      it is time to learn from the mistakes].

PMID- 24734378
TI  - [Botulism is a treatable, very rare type of poisoning. Smoked vacuum packed
      whitefish provided guidance to the diagnosis].

PMID- 24734379
TI  - [Lack of peer influence undermines loyalty to the manager and the organization
      ... but not to the patients].

PMID- 24734380
TI  - [How many "unnecessary" knee arthroscopies are performed really?].

PMID- 24734381
TI  - [Expensive and unnecessary overuse, more pronounced in some regions].

PMID- 24734382
TI  - [Reply from the Health and Social Care Inspectorate on coercive measures: The
      Ministry of Health and Social Affairs has been informed of the issue].

PMID- 24734383
TI  - [Interns' learning should be emphasized in connection with improvement projects].

PMID- 24734384
TI  - [The pioneer in abdominal surgery could not be saved by abdominal surgery].

PMID- 24734385
TI  - [The core of freedom of choice].

PMID- 24734386
TI  - Witnessing down in the delta.

PMID- 24734387
TI  - Patrolling dollars: how should your ACO gear up for ACA?

PMID- 24734389
TI  - Real-world BYOD security BYOD security strategie from two distinct healthcare
      organizations.

PMID- 24734388
TI  - Unlocking cloud computing: an examination of Seattle Children's Hospital's use of
      cloud computing.

PMID- 24734390
TI  - Great expectations for Big Data: will the next wave of analytics lead to a great
      awakening or more strife?

PMID- 24734391
TI  - The risks of legacy processes in a changing ecosystem: in a cloud-based world, a
      new approach to identity management is necessary.

PMID- 24734392
TI  - Homebody: for a large patient, getting out of the house is tricky.

PMID- 24734393
TI  - Home: if you have one at your job-or anywhere-count yourself lucky.

PMID- 24734394
TI  - Making EMS safer.

PMID- 24734395
TI  - All you need to know about bariatrics. Anatomical and physiological differences
      make their care a challenge.

PMID- 24734396
TI  - Acute alcohol poisoning: what can you do for the patient who's had too much?

PMID- 24734397
TI  - Neurotrauma review series part 3: what's in a dermatome? Nerves can tell us much
      about spinal cord injuries.

PMID- 24734398
TI  - 10 Rules for EMS newbies: want to excel in your new field? Try these strategies.

PMID- 24734399
TI  - I get you, babe in work and love, you need a partner who understan.

PMID- 24734400
TI  - Physicians as patients in advance care planning.

PMID- 24734401
TI  - The state of telemedicine in Wisconsin.

PMID- 24734403
TI  - Communication as prevention: the value of talking with each other.

PMID- 24734402
TI  - The national anguish.

PMID- 24734404
TI  - An exploratory study of the use of advance directives by US oncologists.
AB  - PURPOSE: This study sought to determine the rate of advance directive completion
      among US oncologists and factors influencing such a decision. METHODS: We
      surveyed 7590 members of the American Society of Clinical Oncology using a web
      based questionnaire. RESULTS: The response rate was 8.1%. Most respondents (59%)
      had completed at least 1 document: 9% living will, 9% power of attorney for
      health care, and 41% both. Respondents who were older, men, married, with
      children, working in the community setting, radiation oncologists, and practicing
      general oncology were more likely than their counterparts to have an advance
      directive. Among those who had one, 95% and 36% had discussed their wishes with
      their loved ones and health care providers, respectively. Factors including
      experience at work, spouse, children, family, and religion had the most influence
      on respondents' decision. The majority of those without an advance directive
      reported either no reason or lack of time. Those who had them were more likely to
      report having a comprehensive review of their wishes with those closest to them,
      being more knowledgeable, having more routine discussions with their patients,
      and being more comfortable helping their patients complete one. CONCLUSION: Only
      about half of US oncologists who responded to our survey have completed an
      advance directive.

PMID- 24734405
TI  - Nursing home staff perception of a falls management intervention.
AB  - BACKGROUND: Many nursing home fall injuries are believed to be preventable.
      Little is known about the fall prevention activities nursing homes are using.
      METHODS: We conducted a census of all nursing homes in 6 Wisconsin counties by
      mailing a needs assessment to administrators and directors of nursing. Later we
      mailed a report of the results, an information intervention (an annotated list of
      falls management resources), and a follow-up questionnaire. RESULTS: Respondents
      believed that the most important barriers to better falls management in typical
      Wisconsin nursing homes were the fall-prone character of the population (80%),
      followed by the need for staff to communicate changes in a resident's condition
      better and more quickly (58%). Most felt that the components they needed to
      improve in their own nursing home were training for new staff (71%) and
      communicating any immediate care plan changes (65%). Respondents reported getting
      useful fall prevention information in the last year from in-house physical and
      occupational therapists (87%) and conferences, workshops, or meetings (82%). They
      were most interested in receiving new information about how to train their staff
      to analyze resident fall data and develop prevention plans (76%) and where to
      find training videos (68%). Forty-four percent reported becoming personally more
      aware of falls management resources and 31% reported that their nursing home had
      adopted changes in falls management activities in the last 7 months at least in
      part as a result of our intervention. CONCLUSION: Information dissemination
      interventions can increase awareness and changes in nursing home falls management
      activities.

PMID- 24734406
TI  - Geographic and racial variation in teen pregnancy rates in Wisconsin.
AB  - BACKGROUND: Despite recent declines in teen birth rates, teenage pregnancy
      remains an important public health problem in Wisconsin with significant social,
      economic, and health-related effects. OBJECTIVE: Compare and contrast teen birth
      rate trends by race, ethnicity, and county in Wisconsin. METHODS: Teen (ages 15
      19 years) birth rates (per 1000 teenage females) in Wisconsin from 2001-2010 were
      compared by racelethnicity and county of residence using data from the Wisconsin
      Interactive Statistics on Health. RESULTS: Teen birth rates in Wisconsin have
      declined by 20% over the past decade, from 35.5/1000 teens in 2001 to 28.3/1000
      teens in 2010-a relative decline of 20.3%. However, trends vary by race, with
      declines among blacks (-33%) and whites (-26%) and increases among American
      Indians (+21%) and Hispanics (+30%). Minority teen birth rates continue to be 3
      to 5 times greater than birth rates among whites. Rates varied even more by
      county, with an over 14-fold difference between Ozaukee County (7.8/1000) and
      Menominee County (114.2). CONCLUSION: Despite recent declines, teen pregnancy
      continues to be an important public health problem in Wisconsin. Pregnancy
      prevention programs should be targeted toward the populations and counties with
      the highest rates.

PMID- 24734407
TI  - A case of dabigatran-associated acute renal failure.
AB  - Dabigatran is a direct thrombin inhibitor that reduces the risk of systemic
      embolism in patients with nonvalvular atrial fibrillation. We report a case of an
      elderly man who developed unexplained rapid decline in renal function 6 weeks
      after starting dabigatran. A renal biopsy was planned to find out the etiology of
      acute renal failure, but the patient has significantly prolonged coagulation
      parameters despite holding medication for 5 days per manufacturer's
      recommendation. He was started on hemodialysis due to worsening renal function
      and to ensure dabigatran clearance before renal biopsy. Renal biopsy showed renal
      atheroembolic disease, which was possibly induced by dabigatran. Although renal
      atheroembolic disease is a known rare complication following treatment with
      warfarin, heparin, and thrombolytic agents, this is the first reported case of
      renal atheroembolic disease potentially caused by dabigatran. This case also
      highlights the extended duration of prolonged coagulation parameters after
      holding dabigatran and its implication for timing of nonemergent invasive
      procedures.

PMID- 24734408
TI  - A case report of deferasirox-induced kidney injury and Fanconi syndrome.
AB  - Cases of kidney injury associated with the use of deferasirox chelation therapy
      during the course of treatment for iron overload have been reported infrequently.
      We present the case of a patient treated with deferasirox who had biopsy-proven
      tubular injury in the setting of clinical Fanconi syndrome. The patient required
      hospitalization for metabolic acidosis, electrolyte abnormalities, and associated
      symptoms. With supportive care and cessation of chelation therapy he improved,
      but has yet to fully recover. This is the first known case reporting biopsy
      proven tubular damage in the setting of deferasirox use.

PMID- 24734409
TI  - Population health improvement: moving beyond the clinic and into the community.

PMID- 24734410
TI  - MetaStar: celebrating 40 years of improving health care.

PMID- 24734411
TI  - The art of doctoring--inspiring a generation.

PMID- 24734412
TI  - Making progress, but still a way to go.

PMID- 24734413
TI  - Providing premedical students with quality clinical and research experience: the
      Tobacco Science Scholars Program.
AB  - Undergraduate premedical students face a formidable decision as they work to
      determine whether to pursue a profession in medicine. Exposure to clinical
      medicine and research is essential to inform students what it might be like to be
      a physician. Undergraduates, however, face a number of obstacles to obtaining the
      kind of quality clinical and research experience needed to make an informed
      decision. Growing regulations designed to protect patient confidentiality, though
      undeniably important, pose a barrier to students seeking patient contact.
      Traditional passive physician shadowing often does not provide ample
      opportunities for one-on-one patient interaction or problem solving. Finally,
      research opportunities available to students typically are not associated with
      clinical work and therefore do not provide an experiential model of how empirical
      evidence informs medical practice. This report describes the University of
      Wisconsin School of Medicine and Public Health's Tobacco Science Scholars
      Program, a pilot program designed to address some of these barriers. While
      fulfilling institutional requirements for patient contact, the program provides
      students with an active model of clinical patient interaction and problem
      solving, with a research experience integrated into these clinical experiences so
      that undergraduates better understand how research informs clinical medicine.

PMID- 24734414
TI  - Barriers and facilitators of universal HIV screening among internal medicine
      residents.
AB  - BACKGROUND: Adoption of universal HIV screening has been low despite national
      recommendations. OBJECTIVE: To describe the barriers and facilitators to adoption
      of universal HIV screening in a low-prevalence setting. DESIGN: Qualitative,
      thematic analysis of focus group discussions among internal medicine residents
      who introduced universal HIV screening into their primary care practice in
      Madison, Wisconsin. APPROACH: Deductive and inductive codes constructed a
      hybridized thematic analysis model. Deductive codes stemmed from a knowledge
      attitude-behavior framework for physician nonadherence to guidelines. Inductive
      codes emerged from the focus group discussions and were embedded into broader
      deductive codes to provide an HIV-specific model. KEY RESULTS: Residents were
      knowledgeable and had positive attitudes toward recommendations for universal HIV
      screening. Residents felt the majority of their patients were receptive to HIV
      screening, especially when introduced with normalizing techniques and reference
      to an expert authority such as the Centers for Disease Control and Prevention
      (CDC). They still perceived patient discussions as challenging due to stigma
      surrounding HIV and patients' perceptions of being at low risk. Residents
      employed individualized electronic medical record cues as a memory aid to discuss
      the issue. CONCLUSION: This qualitative study of internal medicine residents
      training in an area with low HIV prevalence suggests that stigma and patient
      perception of being at low risk are barriers that should be addressed to
      effectively integrate universal HIV screening into primary care.

PMID- 24734415
TI  - Child abuse pediatric consults in the pediatric emergency department improve
      adherence to hospital guidelines.
AB  - BACKGROUND: Little data describes the role of child abuse pediatricians in
      consultation for physical abuse patients the pediatric emergency department.
      OBJECTIVES: To compare adherence in the emergency department to hospital physical
      abuse guidelines and need to return for testing between 2 groups: those receiving
      a child abuse consultation in the pediatric emergency department vs those who
      received standard emergency department care with subsequent child abuse review.
      METHODS: We reviewed 471 records of visits to the pediatric emergency department
      for physical abuse. Data collected included demographics, studies performed,
      whether patients need to return after child abuse review, child abuse subpoenas,
      child abuse testimony in court. RESULTS: Patients who received a child abuse
      consult in the emergency department or inpatient were more likely to be younger
      and to have more severe injuries. In cases where a consult was obtained, there
      was 100% adherence to emergency department clinical guidelines vs 66% when no
      consult was obtained. In addition, in cases that did not receive a child abuse
      consult, 8% had to return to the hospital for labs or radiographs after their
      emergency department visit. CONCLUSIONS: Child abuse consultation in the
      pediatric emergency department improves compliance with clinical guidelines and
      decreases the likelihood that patients will need to return for further testing.

PMID- 24734416
TI  - Progress in reducing premature deaths in Wisconsin counties, 2000-2010.
AB  - BACKGROUND: Measuring trends in a county's premature death rate is a
      straightforward method that can be used to assess a county's progress in
      improving the health of the population. METHODS: Age-adjusted premature death
      rate data from Wisconsin Interactive Statistics on Health for persons less than
      75 years of age were collected for the years 2000-2010. Overall 10-year percent
      change was calculated, compared, and ranked for all Wisconsin counties during
      this time period. Progress was assessed as excellent (25.0% or greater decline),
      very good (20.0%-24.9% decline), good (10.0%-19.9% decline), fair (0.0%-9.9%
      decline), or poor (any increase). RESULTS: Overall, premature death rates in
      counties declined by 16.8% over the 10-year period 2000-2010 in Wisconsin. Trends
      varied by county, with 8, 15, 37, 9, and 3 counties having excellent, very good,
      good, fair, and poor progress, respectively. The most improvement was seen in
      Kewaunee County (decreasing 38.3%) and the least progress in Lafayette County
      (increasing 4.8%). Trends in premature death rates were not related to the
      county's initial death rate, population, rurality, or income. CONCLUSIONS:
      Although premature death rates declined overall in Wisconsin during the 2000s,
      this progress varied across counties and was not related to baseline mortality
      rates or other county characteristics.

PMID- 24734417
TI  - Heiner syndrome mimicking an immune deficiency.
AB  - Heiner syndrome is a rare but reversible non-IgE mediated hypersensitivity to
      cow's milk resulting in an atypical pulmonary disease in infants and young
      children. There isoften a delay in diagnosis in this disorder due to its unusual
      presentation with heterogeneous manifestations. Such infants usually have chronic
      or recurrent upper or lower respiratory tract symptoms, suggestive of recurring
      infections such as otitis media or pneumonia. The patchy infiltrates on chest x
      ray are commonly mistaken for pneumonia, yet are refractory to
      antibiotictreatment. Systemic features such as fever, vomiting, diarrhea, and
      failure to thrive further contribute to the difficulty in making a prompt
      diagnosis. Only a few case reports have been published. We report a case of this
      unique milk-induced pulmonary syndrome in a hospitalized 12-month-old child,
      which illustrates the importance of considering this diagnosis in any child with
      unexplained lung infiltrates.

PMID- 24734419
TI  - Clinical implementation of whole genome sequencing a valuable step toward
      personalized care.

PMID- 24734418
TI  - Heat-related fatalities in Wisconsin during the summer of 2012.
AB  - BACKGROUND: The hottest year on record for the contiguous United States was 2012.
      July 2012 ranked as Wisconsin's fourth warmest July, which has profound
      implications for heat-related mortality. METHODS: We conducted a case series of
      27 heat-related fatalities in Wisconsin during summer 2012. Data from death
      certificates supplemented by coroner reports were analyzed to characterize
      factors that increase vulnerability to heat-related fatality. RESULTS: The 2012
      heat-related fatalities occurred in both urban and rural counties. All cases had
      1 or more known risk factors: 100% lacked functioning residential air
      conditioning; 70% were over age 65; 75% had a cardiovascular disease; and 52% had
      a mental health condition. Of the 14 cases with a mental health condition, half
      were known to be taking psychotropic medication. None of the decedents had been
      in air conditioning immediately prior to death, and 8 (36%) had been using fans.
      CONCLUSIONS: Air conditioning is known to be a strong protective factor in
      preventing heat-related deaths whereas fans have not been shown to be
      significantly protective across all exposure situations. Prevention efforts
      should stress reducing social isolation by encouraging checks by friends,
      neighbors, or police. Prevention messages should also warn patients on
      psychotropic medications that the medication could increase their risk of heat
      related illness or fatality.

PMID- 24734420
TI  - Driven to serve.

PMID- 24734421
TI  - [Quantitative determination of penicillins by iodometry using potassium hydrogen
      peroxymonosulfate].
AB  - The kinetics and stoichiometry of S-oxidation of semisynthetic penicillins
      (amoxicillin trihydrate, ampicillin trihydrate, sodium salt of oxacillin and
      ticarcillin disodium salt) by potassium hydrogen peroxymonosulfate in aqueous
      solutions at pH 3-6 was studied by iodometric titration: 1 mol of KNSO5 per 1 mol
      of penicillin, the quantitative interaction is achieved in 1 min (time of
      observation). A unified method was developed and the possibility of
      quantification of penicillins by the iodometric method using potassium hydrogen
      peroxymonosulfate as an analytical reagent was shown.

PMID- 24734422
TI  - [Comparative study of immunomodulatory activity of peptides, tinrostim and
      thymalin].
AB  - The immunomodulatory activity of peptide drugs i.e. tinrostim (dosage form)
      prepared of squid optical ganglia and pharmacopoeia thymain was studied.
      Tinrostim showed a stimulating effect on the humoral and cellular nimmune
      responses when administered parenterally in experimental animals, as well as on
      the phagocytic activity of neutrophils, comparable to the effect of thymalin. It
      was demonstrated that both the peptide drugs increased the production of pro
      (TNFa, IL-1) and antiinflammatory (IL- 10) cytokines in the culture of intact
      cells of peripheral blood in vitro. It is essential that when tinrostim was used
      in 10-fold different doses (0.005 mg / kg and 0.05 mg /kg) in mice, the effect of
      the lower dose was comparable to the effect of the higher dose.

PMID- 24734423
TI  - [Dynamics of contamination and persistence of Clostridium difficile in intestinal
      microbiota in newborn infants during antibiotic therapy and use of probiotic
      strain enterococcus faecium L3].
AB  - Ninety four infants were observed as inpatients. Thirty nine of them were mature
      neonates and 55 were premature infants with a very low body weight. The majority
      of the patients were treated with antibiotics. The mature infants were treated
      with penicillins, aminoglycosides, cephalosporins and the premature neonates were
      treated in addition with carbapenems, fluoroquinolones, glycopeptides. The mature
      infants were randomized into 2 groups: the control group (n=18) received the
      standard therapy and the main group (n=21) in addition received 1 ml of liquid
      probiotic Enterococcus faecium L3 (with a titer of 5x10(8) CFU/ml) 2 times a day
      for 10 days. The premature newborn infants were also randomized into 2 groups.
      The control group (n=26) received the standard therapy. The main group (n=29)
      additionally received 1 ml of liquid probiotic E.faecium L3 2 times a day for 10
      days. The effectiveness of the therapy in the mature neonates was evaluated by
      the frequency of dyspeptic disorders and in the premature infants by the
      frequency of infectious complications and the episodes of food intolerance. The
      intestinal microbiota of the infants was investigated by the real-time PCR and
      bacteriological analyses of the feces: in the mature infants on admission to the
      hospital and 10 days after the treatment (periods 1-2), in the premature infants
      on admission to the hospital and then twice with an interval of 14 days (periods
      1-2-3). It was shown that the use of the probiotic strain E.faecium L3 during the
      antibiotic therapy in the premature infants promoted significant reduction in the
      frequency of infectious complications. In the mature neonates the probiotic
      therapy reduced the risk of dyspeptic disorder. The studies showed reduction in
      persistence of Clostridium difficile in the intestinal microbiota of the newborn
      infants receiving the antibiotic therapy in combination with probiotic E.faecium
      L3, that was accompanied by preserving and growth of bifidobacteria and
      lactobacilli and reduction of the number of opportunistic microorganisms.

PMID- 24734424
TI  - [Correction of immunity dysbalance in children with frequent recurrent
      respiratory infection].
AB  - Children with frequent recurrent acute respiratory infections represent an actual
      medical and social problem. Frequent respiratory infections provoke the host
      lower immunity, disturbance of the compensatory-adaptative mechanisms, impairment
      of the physical and neuropsychic development of the child, the social
      disadaptation, chronic pathologic processes in the respiratory organs. High
      efficacy of cycloferon in correction of the immune and interferon responses in
      the frequently ill children was noted.

PMID- 24734425
TI  - [Multiple drug resistance of Mycobacterium tuberculosis isolated from new cases
      of respiratory tract tuberculosis].
AB  - Resistance of Mycobacterium tuberculosis isolated from new cases registered
      during a period from 2007 to 2012 was estimated. High rate of the M.tuberculosis
      multiple drug resistance increase was observed: from 28% in 2007 to 64% in 2012.
      Low efficacy of the treatment of such patients requires revision of the
      tuberculosis control strategy and search for new pharmacological agents groups.

PMID- 24734426
TI  - [Algorithm of identification of atypical variants of Staphylococci, pathogens of
      chronic pyo-inflammatory processes in humans].
AB  - Staphylococcal pathogens of chronic relapsing infections, such as cystic
      pneumosclerosis and osteomyelitis are characterized by atypical morphology of the
      colonies (atypical variants of staphylococci) and present a subpopulation in
      clinically significant staphylococci. Since the loss of some phenotypic
      characteristics important for the genus Staphylococcus due to mutations,
      identification of such staphylococcal variants is difficult and sometimes
      impossible. An algorithm of identification of atypical variants of S.aureus
      (SSCVs) was developed. The advantages of the molecular methods and in particular
      the tRNA-PCR analysis, as well as the use of the diagnostic preparation Diastaph
      for correct identification of Staphylococcus atypical variants were shown.

PMID- 24734427
TI  - [A new approach to postexposure treatment of rabies by complex of immuno- and
      chemotherapy in belarus].
AB  - A method for preventive treatment of rabies with a complex of immuno- and
      chemotherapeutics was developed. Rifampicin was used a an etiotropic drug. In the
      experiments on laboratory animals infected with fixed and street strains of
      rabies virus it was shown to prolong the incubation period and to increase the
      survival rate. The protective mechanisms of rifampicin against rabies should be
      associated with inhibition of RNA transcription, as well as immunomodulating
      function of macrophages, dendritic cells, B- and T-cells. Since 1992, after the
      approval of the Ministry of Health of Belarus rifampicin is used in complex with
      antirabic vaccine for postexposure treatment of rabies in people after severe
      bites by infected animals (wolves, foxes, dogs). For an 18-year period (1992
      2009) of integrated application of chemo- and immunotherapy in Belarus there was
      not registered any case of hydrophobia in people even after the heaviest wolf
      bites, incompatible with life (penetrating injuries of the skull, scalping,
      multiple bites).

PMID- 24734428
TI  - [Molecular and cellular mechanisms of fingolimod action].
AB  - The data on the mechanism of action, efficacy and safety of the drug fingolimod
      are presented. Further study of the molecular, biochemical and cellular
      mechanisms of action of pharmacological regulators of phospholipid mediators'
      signal transduction is an important basis for developing new immunomodulators and
      antitumor agents.

PMID- 24734429
TI  - [The Russian Armed Forces Military Medical Service: condition and ways of
      improvement].
AB  - In 2013 the main efforts of the Medical Service were aimed at the following
      tasks: optimization of management system of military medical service, improvement
      of medical evacuation system, medical service security for military contingents,
      assigned according to territory principle to military-medical facilities of the
      Ministry of Defence of the Russian Federation, implementation of innovations at
      all stages of medical evacuation in peace- and wartime, security of combat and
      mobilization readiness of regulatory bodies of the Medical Service, medical
      military units and military medical facilities, medical service of troops battle
      training, improvement of material and technical resources, security of regular
      pharmacy and equipment supply, activation of research work in the Medical Service
      interests. Lines of military medicine development in 2014 are: transfer of
      treatment facilities that are not used by the Ministry of Defence into the
      Federal Biomedical Agency till the end of 2014, prevention of pneumonia and
      meningitis in military personnel, improvement of early diagnosis system, medical
      service for military contingents according to territory principle, improvement of
      diagnostic and treatment work in military-medical units and subunits and military
      medical facilities by means of development of material and technical resources,
      monitor the implementation of innovative diagnostic and treatment technologies,
      completion of construction projects of central military hospitals and etc.

PMID- 24734430
TI  - [Current state and prospects of military personnel health monitoring].
AB  - The current article is dedicated to some features of the Russian Federation Armed
      Forces military personnel health monitoring such as legal and informational
      provision, methodological basis of functioning, historical aspect of formation
      and development of the social and hygienic monitoring in the Russian Federation
      Armed Forces. The term "military personnel health monitoring" is defined as an
      analytical system of constant and long-term observation, analysis, assessment,
      studying of factors determined the military personnel health, these factors
      correlations, health risk factors management in order to minimize them. The
      current state of the military personnel health monitoring allows coming to the
      conclusion that the military health system does have forces and resources for
      state policy of establishing the population health monitoring system
      implementation. The following directions of the militarily personnel health
      monitoring improvement are proposed: the Russian Federation Armed Forces medical
      service record and report system reorganization bringing it closer to the
      civilian one, implementation of the integrated approach to the medical service
      informatisation, namely, military personnel health status and medical service
      resources monitoring. The leading means in this direction are development and
      introduction of a military serviceman individual health status monitoring system
      on the basis of a serviceman electronic medical record card. Also it is proposed
      the current Russian Federation Armed Forces social and hygienic monitoring
      improvement at the expense of informational interaction between the two
      subsystems on the basis of unified military medical service space.

PMID- 24734431
TI  - [Mistakes and complications in internal osteosynthesis in patients with fractures
      of long bones].
AB  - Authors analyzed unsatisfied anatomical and functional treatment results of 118
      patients after the internal osteosynthesis for fractures of long bones of
      extremities, which required ion performed revision surgery. Patients were
      examined clinically and instrumental before revision osteosynthesis, in short
      term and long-term period after the operation. Authors systemized revealed
      mistakes into 4 groups and found out that the most frequent were tactical and
      technical (84.7%) mistakes, much less--diagnostic and organizational. Developed
      algorithm of preoperative evaluation, planning, technology, revision
      reconstructive operations allowed shortening recover time of anatomy and function
      to the average in 92.6% of patients.

PMID- 24734432
TI  - [Hip replacement in military personnel].
AB  - Hip joint diseases and injuries are common for orthopedic pathology among
      military personnel. Hip replacement is one of the most frequent operations.
      Authors evaluated hip replacement in 136 servicemen treated at the center of
      traumatology and orthopedics of Burdenko General Military Clinical Hospital of
      the Ministry of Defense of Russia in 2010-2013. On the basis of the conducted
      analysis the main disease groups were revealed, peculiarities of pathology among
      this category of patients. Authors proposed surgical doctrine for the treatment
      of this contingent. Effective surgical treatment, in particular, hip replacement
      surgery, conducted with the use of the proposed principles, as a rule, fully
      functionally cured patients and contributes to return them in the system that
      contributes to the strengthening of defensibility of the country.

PMID- 24734433
TI  - [Diphtheria in the military forces: lessons and current status of prophylaxis,
      prospects of epidemiological control process].
AB  - We analyzed the epidemiological situation of diphtheria in the world and in
      Russia and experience of mass vaccination of military personnel and civil
      population with diphtheria toxoid for the last 50 years. Early diagnosis of
      diphtheria in military personnel has a prognostic value. Authors described the
      peculiarities of epidemiological process of diphtheria in military personnel in
      80-90 years of 20th century and organizational aspects of mass vaccination with
      diphtheria toxoid. Authors analyzed current problems of epidemiology and
      prophylaxis of diphtheria in military personnel and civil population and possible
      developments. According to long-term prognosis authors mentioned the increase of
      morbidity and came to conclusion that it is necessary enhance the epidemiological
      surveillance. Authors presented prospect ways of improvement of vaccination and
      rational approaches to immunization of military personnel under positive long
      term epidemiological situation.

PMID- 24734434
TI  - [Improvement of the health care delivery system in war-time: monitoring of
      servicemen's health status].
AB  - Authors came to conclusion that the constant monitoring of servicemen's health
      status allows the commanding officer to receive detailed information about combat
      effectiveness. In case of battle injury or trauma the information used by the
      medical service will be the base for early health care delivery and organization
      of evacuation. The information about health status of injured may be used as a
      base for diagnosis at all stages of evacuation. Authors came to conclusion that
      individual monitoring of health status will help to further health care delivery
      system and first stages of medical evacuation.

PMID- 24734435
TI  - [The modern approaches to the principles of medical and surgical casualty
      estimation. The US and British experience].
AB  - The current article is dedicated to the principles of medical and surgical
      casualty estimation elaborated by the medical services of the US and Great
      Britain Armed Forces on the basis of their experience obtained during Afghanistan
      and Iraq operations.

PMID- 24734436
TI  - [Experience in provision of medical services to earthquake victims in Armenia in
      1988].
AB  - The most devastating catastrophe in the USSR was the Armenian earthquake occurred
      on 7th December 1988. The city of Leninakan and towns of Kirovokan, Spitak (the
      epicenter), Stepanovan were destroyed by the earthquake with a magnitude 10. Up
      to 25 542 people have died, more than 500 000 were homeless and 39 795 were
      rescued. Medical service of the Ministry of Defence of the USSR took part in
      rescue work. Medical service units finished their rescue work on 31st December
      after results of work were summed up. Lethality rate was an index of successful
      rescue work of the unit. Only 6% of injured rescued by the medical unit have
      died, meanwhile 40%-50% of injured have died in Erevan hospitals. Mortality rate
      in patients with crush syndrome was 8.9% (according to other authors--30-75%). 75
      injured remained in hospital, 25 injured were evacuated to central military
      hospitals for reconstructive plastic surgery. Officers of the medical unit,
      embodied from the main and central hospitals, successfully completed the task and
      received experience in provision of medical services to earthquake victims.

PMID- 24734437
TI  - [European Congress for trauma and emergency surgery].

PMID- 24734438
TI  - [Brown spots on the whole body: the mother has them as well. Neurofibromatosis].

PMID- 24734439
TI  - [Study in general practice: healing the common cold: landing on the moon is
      easier].

PMID- 24734440
TI  - [No stent for unpopular politicians?].

PMID- 24734441
TI  - [Regresses for medicine prescription: benchmark evaluations should be
      eliminated].

PMID- 24734442
TI  - [E-mail and internet: online security in the general practice office].

PMID- 24734443
TI  - [Do you have advice when the patient asks: "Doctor, how high is my risk?"].

PMID- 24734444
TI  - [Your patient needs an antithrombotic drug, 9. Atrial fibrillation: unnecessary
      hesitation regarding anticoagulants?].

PMID- 24734445
TI  - [Atrial fibrillation: catheter ablation: release from anticoagulation?].

PMID- 24734446
TI  - [Galenus prize 2013: impulse for progress].

PMID- 24734447
TI  - [Infection prophylaxis: anyone who has brains in his head, coughs into his
      elbow!].

PMID- 24734448
TI  - [Rainbow colored halo: what causes it?].

PMID- 24734449
TI  - [Patient maintains the generic drug is ineffective: is there an explanation for
      this?].

PMID- 24734450
TI  - [Patient syncope during an injection: may I administer further vaccinations?].

PMID- 24734452
TI  - [Balance after ten years of pneumococcal vaccination].

PMID- 24734451
TI  - [Weight loss of unknown origin in a type 1 diabetic patient: then suddenly the
      metabolism derailed].

PMID- 24734453
TI  - [Is there a "healthy" obese?].

PMID- 24734454
TI  - [Are questions better than the glucose tolerance test?].

PMID- 24734455
TI  - [Be careful with hospital self-discharge].

PMID- 24734456
TI  - [Depression as a compliance obstacle].

PMID- 24734457
TI  - [Post-Treatment Lyme Disease Syndrome only a phantom?].

PMID- 24734458
TI  - [Influenza].

PMID- 24734459
TI  - [Skin aging].

PMID- 24734460
TI  - [Inflammatory bowel diseases].

PMID- 24734461
TI  - [Use of strong opioids in general practice].

PMID- 24734462
TI  - [Diagnostic and treatment of female urinary incontinence].

PMID- 24734463
TI  - [Chronic heart failure].

PMID- 24734464
TI  - [The anxiously depressed patient and the general practitioner].

PMID- 24734465
TI  - [Sarcoidosis--a state-of-the art review].

PMID- 24734466
TI  - Bay oysters, the polar vortex, and sustainable engineering.

PMID- 24734467
TI  - Removal of triclocarban and triclosan during municipal biosolid production.
AB  - The antimicrobial compounds triclosan (TCS) and triclocarban (TCC) accumulate in
      sludges produced during municipal wastewater treatment and persist through sludge
      treatment processes into finished biosolids. The objective of this research was
      to determine the extent to which conventional sludge processing systems such as
      aerobic digestion, anaerobic digestion, and lime stabilization were able to
      remove TCC and TCS. The concentrations of TCC and TCS in sludge and biosolid
      samples were determined via heated solvent extraction and analysis with liquid
      chromatography electrospray ionization mass spectrometry. The removal of TCC and
      TCS in municipal biosolid processing systems was determined from the measured
      concentration change after correcting for reductions in solid mass during sludge
      treatment. Removal in the digester systems ranged from 15 to 68% for TCC and 20
      to 75% for TCS. Increased solid retention times during sludge treatment
      operations were correlated with higher removals of TCC and TCS.

PMID- 24734468
TI  - Oxygen and carbon requirements for biological nitrogen removal processes
      accomplishing nitrification, nitritation, and anammox.
AB  - The oxygen and carbon savings associated with novel nitrogen removal processes
      for the treatment of high ammonia, low biodegradable organic matter waste streams
      such as the recycle streams from the dewatering of anaerobically digested sludges
      are well documented.This understanding may lead some to think that similar oxygen
      savings are possible if novel processes such as nitritation/ denitritation and
      partial nitritation-deammonification are incorporated into main liquid stream
      processes where influent biodegradable organic matter is used to denitrify
      residual oxidized nitrogen (nitrite and nitrate). It is demonstrated that the net
      oxygen required for nitrogen removal is 1.71 mg O2/mg ammonia-nitrogen converted
      to nitrogen gas as long as influent biodegradable organic matter is used to
      denitrify residual oxidized nitrogen. Less oxygen is required to produce oxidized
      nitrogen with these novel processes, but less biodegradable organic matter is
      also required for oxidized nitrogen reduction to nitrogen gas, resulting in
      reduced oxygen savings for the oxidation of biodegradable organic matter. The net
      oxygen requirement is the same since the net electron transfer for the conversion
      of ammonia-nitrogen to nitrogen gas is the same. The biodegradable organic matter
      required to reduce the oxidized nitrogen to nitrogen gas is estimated for these
      processes based on standard biological process calculations. It is estimated to
      be in the range of 3.5 to 4.0 mg biodegradable COD/mg ammonia-nitrogen reduced to
      nitrogen gas for nitrification-denitrification, 2.0 to 2.5 for nitritation
      denitritation, and 0.5 for partial nitritation-deammonification. The resulting
      limiting influent wastewater carbon-to-nitrogen ratios are estimated and can be
      used to guide the appropriate selection of biological nitrogen removal process
      given knowledge of the biological process influent wastewater carbon-to-nitrogen
      ratio. Energy savings possible for mainstream processes incorporating these novel
      nitrogen removal processes include reduced process oxygen requirements from
      reduced biodegradable carbon loadings to the biological process and the potential
      that plant influent biodegradable carbon can be captured upstream of the
      biological nitrogen removal process and used to produce energy, for example, by
      conversion into biogas.

PMID- 24734469
TI  - Microwave effects on soluble substrate and thermophilic digestibility of
      activated sludge.
AB  - Thickened waste-activated sludge (TWAS) was subjected to microwave pretreatment
      and athermal irradiation. The soluble phase of each type of TWAS pretreatment was
      subject to ultrafiltration in series using progressively smaller pore-size
      membranes (300, 100, 10, and 1 kDa) and biodegradability tests. Microwave
      pretreatment solubilizes a considerable amount of the suspended organic
      substrate, but athermal irradiation also causes solubilization of organic matter,
      although at a smaller scale than microwave. Proteins are particularly sensitive
      to athermal irradiation, and both microwave and athermal irradiation are capable
      of changing the size distribution of dissolved organic matter. Athermal
      irradiation and microwave have a substantially different effect on thermophilic
      anaerobic biodegradability of the various size fractions obtained after
      ultrafiltration. Slight inhibition and decrease in total biogas production was
      measured in some microwave tests. Athermal irradiation does not cause a decrease
      in maximum biogas production rate in any test and increases slightly biogas
      production.

PMID- 24734470
TI  - Soluble microbial products from water biological treatment process: a review.
AB  - The relationship between soluble microbial products (SMPs) and extracellular
      polymeric substances is described, and the characteristics of SMPs in the
      biological wastewater treatment process, including molecular weight distribution,
      metal-chelating property, biodegradability, biotoxicity, and membrane fouling,
      are investigated. The SMPs produced by autotrophs are degradable and utilizable
      for heterotrophs, thereby confirming the biodegradation of SMPs. Soluble
      microbial product models are designed through three approaches: establishment of
      SMP kinetic models or combination with Monod equations, incorporation of SMP
      generation and degradation into the unified theory raised by Laspidou and
      Rittmann (2002a), and introduction of the concept of SMP into activated sludge
      models. The effects of process parameters on SMP concentration are elaborated,
      based on the optimum biological treatment process operating parameters that can
      effectively minimize SMP production. The progress of SMP research in water
      biotreatment systems is presented, and suggestions for future studies are made.

PMID- 24734471
TI  - Modeling energy consumption in membrane bioreactors for wastewater treatment in
      north Africa.
AB  - Two pilot-scale membrane bioreactors were operated alongside a full-sized
      activated sludge plant in Tunisia in order to compare specific energy demand and
      treated water quality. Energy consumption rates were measured for the complete
      membrane bioreactor systems and for their different components. Specific energy
      demand was measured for the systems and compared with the activated sludge plant,
      which operated at around 3 kWh m(-3). A model was developed for each membrane
      bioreactor based on both dynamic and steady-state mass balances, microbial
      kinetics and stoichiometry, and energy balance. Energy consumption was evaluated
      as a function of mixed-liquor suspended solids concentration, net permeate
      fluxes, and the resultant treated water quality. This work demonstrates the
      potential for using membrane bioreactors in decentralised domestic water
      treatment in North Africa, at energy consumption levels similar or lower than
      conventional activated sludge systems, with the added benefit of producing
      treated water suitable for unrestricted crop irrigation.

PMID- 24734472
TI  - Simultaneous biological nutrient removal: a state-of-the-art review.
AB  - Simultaneous biological nutrient removal (SBNR) is the occurrence of biological
      nutrient removal (BNR) in systems that do not possess defined anaerobic and/or
      anoxic zones. A review of the relevant literature demonstrates that two
      mechanisms are primarily responsible for SBNR: (1) the bioreactor macro
      environment and (2) the floc microenvironment. Complex hydraulic flow patterns
      exist in full-scale bioreactors that can result in the cycling of mixed liquor
      through the different environments needed for BNR. Diffusion resistance further
      allows oxygen-sufficient and oxygen-deficient zones to develop in activated
      sludge flocs if the external dissolved oxygen concentration is properly
      controlled. The diffusion of substrates between these zones allows BNR to occur.
      Long-term acclimation to the unique environmental conditions occurring in these
      systems results in the selection of microorganisms well adapted to the low
      dissolved oxygen concentrations occurring in them. The experience base for the
      design and operation of SBNR systems is expanding, thereby allowing their more
      widespread application, especially coupled with conventional mathematical
      modeling approaches. Computational fluid dynamics is an evolving tool to assist
      with the design and optimization of SBNR.

PMID- 24734473
TI  - Characterization of the microbial community in the rhizosphere of Phragmites
      australis (cav.) trin ex. steudel growing in the Sun Island Wetland.
AB  - Rhizospheric microorganisms are important for environmental conservancy. The
      constancy and variability of the microorganisms in the rhizosphere of Phragmites
      australis in relation to the spatiotemporal variations in wetland ecosystems were
      studied. During the peak and trough of the vegetative period of the Phragmites
      australis growing across the hydrologic gradients of the Sun Island Wetland,
      Biolog and denaturing gradient gel electrophoresis (DGGE) were used to
      investigate the rhizospheric microbial characteristics. Both methods demonstrated
      that the microbial activity, richness, and diversity decreased from summer to
      autumn. However, these properties did not show significant correlation with
      hydrologic gradient, except that the genetic richness and diversity of the fungi
      decreased with it. Cluster analysis also demonstrated that the rhizospheric
      microbial community seemed to be largely affected by a vegetative period. In
      addition, this research was extended to a broader range of determining the
      universal microorganisms, which showed notable adaptability.

PMID- 24734474
TI  - Hydrochemical versus biological conditions of the functioning of three shallow
      lakes in Leczna-Wlodawa.
AB  - Lake-catchment relationships were presented with reference to each part of the
      subsystem. Ionic loads reflected the potential of the catchment areas and
      displayed the following pattern: Lake Rotcze < Lake Sumin < Lake Syczynskie; with
      respect to every ion, except nitrogen. The highest specific load of ions in Lake
      Syczynskie and the strong hydrochemical influence of the lake inlets facilitated
      the growth of water blooms of cyanobacteria, with a dominance of toxic
      filamentous P agardhii. It resulted in a poor ecological status of the lake (Q
      index = 0.8) and its hypertrophy (TSIchl-a = 78). The specific load of ions in
      the Lake Rotcze catchment (0.23 kg/yr-km(2) of P-PO4) contributed to the good
      ecological status (Q = 3.2) and mesotrophic character (TSIchl.a = 50) of the
      lake. Lake Sumin has a moderate catchment influence (2.41 kg/yr-km(2) of P-PO4),
      which facilitated moderate ecological (Q = 2.1) and trophic (eutrophy; TSIchlSa =
      63) status.

PMID- 24734475
TI  - Biodegradation characteristics of naphthalene and benzene, toluene, ethyl
      benzene, and xylene (BTEX) by bacteria enriched from activated sludge.
AB  - Naphthalene and BTEX (benzene, toluene, ethyl benzene, and xylene) are frequently
      detected toxic hydrocarbons in contaminated sites, which can easily enter the
      soil or groundwater system. To test the potential of treating these hydrocarbons
      in a conventional water resource recovery facility, municipal activated sludge
      was used as the seed and the bacteria successfully enriched using naphthalene or
      BTEX as the sole carbon source under aerobic conditions. The pseudo first order
      kinetic constant for naphthalene degradation by enriched bacteria was 14.053 L h(
      1) g(-1). For BTEX degradation, kinetic constants of 0.234, 0.958, 1.212, and
      0.455 L h(-1) g(-1)1' were obtained for benzene, toluene, ethyl benzene, and
      xylene, respectively, which collectively accounted for a total BTEX removal rate
      constant of 0.550 L h(-1) g(-1) . Through cloning and sequencing, Pseudomonas and
      Burkholderia were identified as the primary bacteria communities in the
      naphthalene degradation reactor, whereas for BTEX degradation, Pseudomonas and
      Acidovorax dominated in the reactor.

PMID- 24734476
TI  - Of: variations in highway stormwater runoff quality and stormwater treatment
      performance in relation to the age of porous friction courses, J. P. Moores, P.
      E. Pattinson, C. R. Hyde, 85, 772-781 (2013); corrected at 86, 285 (2014).

PMID- 24734477
TI  - Routine active management of the third stage.

PMID- 24734478
TI  - Marion's message: developing midwifery judgment.

PMID- 24734479
TI  - Motherbaby placenta: state of emergency.

PMID- 24734480
TI  - The placenta encapsulation movement.

PMID- 24734481
TI  - Placentophagy.

PMID- 24734482
TI  - Group B strep: a holistic approach.

PMID- 24734483
TI  - Placentas I have known.

PMID- 24734485
TI  - Honoring placenta wisdom.

PMID- 24734484
TI  - Mercy in action midwives form disaster response to deadly super typhoon.

PMID- 24734486
TI  - Lanyero Karamela: a midwife of Uganda.

PMID- 24734487
TI  - Thoughts on homebirth transfer.

PMID- 24734488
TI  - Research on placenta encapsulation.

PMID- 24734489
TI  - Microphones on pregnant bellies.

PMID- 24734490
TI  - Consuming placenta.

PMID- 24734491
TI  - It's ours: we claim the benefits.

PMID- 24734492
TI  - My retained placenta.

PMID- 24734493
TI  - Our placenta journey.

PMID- 24734494
TI  - Surprise...it's a placenta!

PMID- 24734495
TI  - Herbs and the placenta.

PMID- 24734496
TI  - Placenta handling.

PMID- 24734497
TI  - A watched pot: the importance of a sacred, private labor and birth.

PMID- 24734498
TI  - Supporting Muslim families as midwives.

PMID- 24734499
TI  - The gift of the womb.

PMID- 24734500
TI  - Amniotic membrane use for perineal healing: a re-discovery.

PMID- 24734501
TI  - A midwife between worlds.

PMID- 24734502
TI  - The placental pause.

PMID- 24734503
TI  - Guardians of birth.

PMID- 24734504
TI  - The breech birth of Edith.

PMID- 24734505
TI  - Birth workers of color scholarship: matching scholars to scholarships to reduce
      disparities in birth outcomes.

PMID- 24734506
TI  - Delayed cord clamping.

PMID- 24734507
TI  - Recent advances in the nanotechnology-based drug delivery of Silybin.
AB  - Silybin is the main component of silymarin and is a polyphenolic bioactive
      natural product found in the milk thistle plant Silybum marianum. Silybin
      possesses many health-promoting benefits, such as antioxidation and anticancer.
      However, the benefits are curtailed by its extremely poor water solubility.
      Consequently, the bioavailability and therapeutic effective of silybin is also
      limited. Nanotechnology is an available approach to solving these issues.
      Currently, nanosuspensions, micelles, nanoparticles, nano-emulsions, etc. are
      used to improve the in vitro dissolution velocity and in vivo efficiency of
      silybin. The present work reviews the nanotechnology-based applications and
      developments on silybin production. Silybin can also be utilized as a reference
      for the production and development of other water-insoluble drug delivery
      systems.

PMID- 24734508
TI  - Silymarin encapsulated poly(D,L-lactic-co-glycolic acid) nanoparticles: a
      prospective candidate for prostate cancer therapy.
AB  - Silymarin, a clinically proved hepato-protective herbal drug having significant
      anti-cancerous property towards prostate cancer, is inadequately utilized for
      cancer therapy due to its hydrophobic nature and poor bioavailability. In this
      work, we have developed silymarin Poly(D,L-lactic-co-glycolic acid) (PLGA)
      nanoparticles (NPs) in order to improve the therapeutic efficacy of silymarin
      towards prostate cancer by single emulsion solvent evaporation technique. The
      prepared nanoparticles had an encapsulation efficiency of 60% and a loading
      efficiency of 13%. The silymarin-PLGA NPs (SNPs) characterization, using DLS and
      SEM analysis revealed its size as less than 300 nm. FT-IR analysis confirmed
      encapsulation of silymarin by the SNPs, whereas XRD and TGA proved amorphous
      nature of the SNPs. In vitro drug release study demonstrated a slow and sustained
      release of encapsulated drug from the SNPs in physiological conditions. The
      hemocompatibility of the SNPs was established by in vitro hemolysis and
      coagulation assays. In vitro cell viability studies revealed preferential
      toxicity of SNPs towards prostate cancer cells (PC-3) compared to normal cells
      (Vero) in a dose dependant way. Cell uptake studies using confocal microscopy
      confirmed internalization of the SNPs by PC-3 cells. Furthermore, in vitro cell
      migration assay showed a concentration and time dependent inhibitory effect of
      SNPs on PC-3 cell migration. Finally, flow-cytometry based apoptosis assay
      suggested induction of apoptosis mediated death in PC-3 cells by the SNPs.
      Overall, the prepared SNPs proved as a promising candidate for prostate cancer
      therapy.

PMID- 24734509
TI  - Substrate-mediated delivery of microRNA-145 through a polysorbitol-based
      osmotically active transporter suppresses smooth muscle cell proliferation:
      implications for restenosis treatment.
AB  - Smooth muscle cells (SMCs) can grow over a stent surface and block blood flow
      through the stent, resulting in restenosis. MicroRNAs (miRNAs) are post
      transcriptional regulators that contribute to cell proliferation, survival, and
      metabolism. Several miRNAs, including miR-145, have been identified that regulate
      vascular SMC proliferation and are down-regulated under conditions of
      proliferation. We hypothesized that SMC proliferation would be reduced or
      diminished if miR-145 expression was restored in SMCs. We designed a method to
      coat the stent surface with miR-145 to suppress the over-growth of SMCs. For
      effective miRNA delivery, various types of nanocarriers were tested for enhanced
      transfection efficiency and biocompatibility in the case of surface-mediated
      delivery. Physico-chemical characterization of the prepared nanoparticles was
      performed, and the cell viabilities and transfection efficiencies of the carriers
      were studied and compared to select the most efficient carrier for substrate
      mediated delivery. The polysorbitol-based osmotically active transporter (PSOAT)
      retained its transgene delivery capacity and had higher biocompatibility than the
      other tested carriers. We detected reporter and therapeutic gene expression at
      the stent surface following PSOAT-mediated delivery. SMC proliferation after the
      treatment with PSOAT/miR-145 nanoparticles (PMN) was monitored using the MTS
      assay, and miR-145 target gene expression after PMN treatment was measured by
      reverse transcription-polymerase chain reaction. PSOAT-mediated delivery of miR
      145 was associated with efficient intracellular expression of the therapeutic
      gene. A drastic reduction in SMC proliferation was observed after PMN treatment,
      and miR-145 target proteins were down-regulated upon miR-145 replacement.

PMID- 24734510
TI  - Anti-tumor activity and safety evaluation of fisetin-loaded methoxy poly(ethylene
      glycol)-poly(epsilon-caprolactone) nanoparticles.
AB  - Fisetin (3,3',4',7-tetrahydroxyflavone) is a potential anti-tumor agent but poor
      water solubility hinders its application and complicates direct parenteral
      administration. Nanoparticle encapsulation is an efficient way to enhance the
      solubility of some hydrophobic drugs. In this study, methoxy poly(ethylene
      glycol)-polycaprolactone (MPEG-PCL) nanoparticles were successfully prepared for
      fisetin delivery in vitro and in vivo. Narrow distribution fisetin-loaded MPEG
      PCL NPs (aproximately100 nm) were obtained via emulsification (O/W) and displayed
      a sustained release behavior in vitro. Moreover, hemolysis and cell cytotoxicity
      testing showed that MPEG-PCL is biocompatible and safe for intravenous injection.
      Most importantly, NPs encapsulation enhanced the anti-cancer activity of fisetin
      as shown in a subcutaneous LL/2 tumor model, and reduced the hepatotoxicity of
      fisetin. Therefore, our data demonstrate that fisetin-loaded MPEG-PCL NPs have
      potential application in cancer chemotherapy.

PMID- 24734511
TI  - Dexamethasone-loaded poly(D, L-lactic acid) microspheres/poly(ethylene glycol)
      poly(epsilon-caprolactone)-poly(ethylene glycol) micelles composite for skin
      augmentation.
AB  - Soft tissue augmentation using various injectable fillers has gained popularity
      as more patients seek esthetic improvement through minimally invasive procedures
      requiring little or no recovery time. The currently available injectable skin
      fillers can be divided into three categories. With careful assessment,
      stimulatory fillers are the most ideal fillers. In this study, dexamethasone
      loaded poly(D, L-lactic acid) (PLA) microspheres of approximately 90 micro m
      suspended in poly(ethylene glycol)-poly(epsilon-caprolactone)-poly(ethylene
      glycol) (PEG-PCL-PEG, PECE) micelles were prepared as stimulatory filler for skin
      augmentation. The biodegradable PECE copolymer can form nano-sized micelles in
      water, which instantly turns into a non-flowing gel at body temperature due to
      micellar aggregation. The PECE micelles (making up 90% of composite) served as
      vehicle for subcutaneous injection were metabolized within 44 days. At the same
      time, the dexamethasone-loaded PLA microspheres (10% of composite) merely served
      as stimulus for connective tissue formation. Dexamethasone-loaded PLA
      microspheres/PECE micelles composite presented great hemocompatibility in vitro.
      It was demonstrated in the in vive study that the composite was biodegradable,
      biocompatible, nontoxic and nonmigratory. Histopathological studies indicated
      that the composite could stimulate collagen regeneration. Furthermore, granuloma,
      the main complication of the stimulatory fillers, did not appear when the
      composite was injected into the back of SD rats, because of the dexamethasone
      controlled release from the composite. All results suggested that dexamethasone
      loaded PLA microspheres/PECE micelles composite may be an efficient and promising
      biomaterial for skin augmentation.

PMID- 24734512
TI  - Cell infiltration and vascularization in porous nanoyarn scaffolds prepared by
      dynamic liquid electrospinning.
AB  - A novel electrospun nanoyarn scaffold, aimed to improve cell infiltration and
      vascularization, as well as guide cell behaviors by its biomimetic structure, was
      fabricated for tissue engineering. Electrospun nanofibers were deposited and
      twisted into yarns in a water vortex before collecting on a rotating mandrel to
      form a nanoyarn scaffold. Field emission-scanning electronic microscope (FE-SEM)
      images revealed that the scaffold, composed of aligned nanoyarns (24 micro m)
      which were composed of a bundle of nanofibers, created a porous structure which
      may be conducive to cellular infiltration. Thus, we hypothesized that the
      biomimetic nanoyarn will have a positive influence on cell proliferation and
      morphology. Pig iliac endothelial cells (PIECs) and MC3T3-E1 pre-osteoblastic
      cells cultured on the nanoyarn scaffolds showed significantly higher
      proliferation rates than that on traditional electrospun nanofiber scaffolds.
      Histological analysis demonstrated that cells infiltrate throughout the nanoyarn
      scaffolds over a 10-day period, however, no cell infiltration was observed on the
      nanofiber scaffolds. Moreover, confocal microscopy images indicated that both
      PIECs and MC3T3-E1 pre-osteoblastic cells cultured on the nanoyarn scaffolds
      exhibit an extremely elongated morphology compared to the flattened morphology
      when cells were cultured on electrospun nanofiber scaffolds or tissue culture
      plates. Furthermore, complex capillary-like structures were observed when PIECs
      cultured on the nanoyarn scaffold for 7 days, indicating that the nanoyarns
      provide templates and topographical cues for the assembly of PIECs and the
      promotion of a capillary network in vitro. In conclusion, the positive cellular
      interactions on the nanoyarn scaffold demonstrate potential application for use
      in tissue engineering.

PMID- 24734513
TI  - Dual channel sensitive detection of hsa-miR-21 based on rolling circle
      amplification and quantum dots tagging.
AB  - An isothermal, highly sensitive and specific assay for the detection of hsa-miR
      21 with the integration of QDs tagging and rolling circle amplification was
      offered. In addition, a dual channel strategy for miRNA detection was proposed:
      anodic stripping voltammetry (ASV) and fluorescent method were both performed for
      the final Cd2+ signal readout. The designed strategy exhibited good specificity
      to hsa-miR-21 and presented comparable detection results by detection methods.

PMID- 24734514
TI  - Increased cortical neuronal survival during liver injury: effect of gamma
      aminobutyric acid and 5-HT chitosan nanoparticles.
AB  - Use of nanoparticulate drug delivery system for an effective therapeutic outcome
      against diseases gains immense hope in the study of drug delivery to partially
      hepatectomised rats. In the present study, partially hepatectomised rats treated
      with Gamma aminobutyric acid (GABA) and serotonin (5-HT) chitosan nanoparticles,
      individually and in combination, were evaluated to analyse their role in GABAB,
      and 5-HT2A receptors functional regulation, interrelated neuronal survival
      mechanisms by nuclear factor kappa B (NF-kappaB), tumour necrosis factor-a (TNF
      alpha), Akt-1 and the antioxidant enzyme superoxide dismutase (SOD) in the
      cerebral cortex. A significant decrease in GABA, and 5-HT2A receptor numbers and
      gene expressions denoted a homeostatic adjustment by the cerebral cortex to
      trigger the sympathetic innervations during elevated DNA synthesis in the liver.
      GABAB, and 5-HT2A signalling directly influenced the cyclic AMP response element
      binding protein (CREB) expression, neuronal survival and ROS mediated cell damage
      which was confirmed from the gene expression of NF-kappaB, TNF-alpha, Akt-1 and
      SOD. In addition to enhanced hepatocyte proliferation, GABA and 5-HT chitosan
      nanoparticle treatment protected the neurons from ROS mediated cell damage and
      promoted their survival in the cerebral cortex. This has application in liver
      based diseases and treatments with nanosized active compounds.

PMID- 24734515
TI  - Preparation of curcumin-loaded poly(ester amine) nanoparticles for the treatment
      of anti-angiogenesis.
AB  - The aim of this study was to prepare curcumin loaded poly(ester amine)
      nanoparticles and enhance their hydrophilicity and treatment efficacy on anti
      angiogenesis zebra fish model. Poly(ester amine) (PEA) copolymer was synthesized
      in this study. The curcumin-loaded PEA nanoparticles were prepared through double
      emulsion-solvent evaporation technique. The average particle size of obtained
      nanoparticles was about 100 nm. The zeta potential of prepared nanoparticles was
      about 35.8+/-2.4 mV. Transmission electron microscopy demonstrated a narrow size
      distribution with in vitro release profile demonstrating in vitro slow release of
      curcumin from the PEA nanoparticles. The in vitro cytotoxicity of the curcumin
      encapsulated PEA nanoparticles nearly had the same tendency of cytotoxic activity
      in vitro with free curcumin on tumor cells. In vitro cellular uptake of the
      curcumin-loaded nanoparticles demonstrated in Hela cells demonstrated that this
      kind of nanoparticles can be a promising candidate as a drug delivery system to
      cancer cells. The Cur/PEA nanoparticles more efficiently inhibited angiogenesis
      (in vivo) in transgenic zebra fish model and Alginate-encapsulated tumor cells
      than free curcumin. No mortality or significant lesions were observed from
      histopathological study of the major organs. From our results, we can conclude
      that the prepared PEA nanoparticles are an efficient curcumin drug delivery
      system for anti-angiogenesis therapy.

PMID- 24734516
TI  - pH sensitive thiolated cationic hydrogel for oral insulin delivery.
AB  - The objective of this work is to study the efficacy of pH sensitive thiolated
      Polydimethylaminoethylmethacrylate for oral delivery of insulin. Synthesis of pH
      sensitive thiolated Polydimethylaminoethylmethacrylate (PDCPA) was carried out by
      crosslinking Polymethacrylic acid with thiolated
      Polydimethylaminoethylmethacrylate (PDCys) via carbodiimide chemistry. Prior to
      in vivo experiment, various physicochemical and biological characterisation were
      carried out to evaluate the efficacy of PDCPA. Modification was confirmed by IR
      and NMR spectroscopy. The particle size was found to be 284 nm with a zeta
      potential of 37.3+/-1.58 mV. Texture analyser measurements showed that PDCPA is
      more mucoadhesive than the parent polymer. Transepithelial electrical
      measurements showed a reduction of greater than 50% on incubation with PDCPA
      particles. Permeation studies showed that PDCPA is more permeable than the parent
      polymer. On in vivo evaluation on male diabetic rats, insulin loaded PDCPA
      exhibited a blood glucose reduction of 19%.

PMID- 24734517
TI  - Variation of mechanical property of single-walled carbon nanotubes-treated cells
      explored by atomic force microscopy.
AB  - With a range of biological properties, single-walled carbon nanotubes (SWCNTs)
      are a promising material for nanobiotechnology. Concerns about their potential
      effect on human health have led to the interest in understanding the interaction
      between SWCNTs and cells. There are many reports showing the potential cellular
      effects of SWCNTs but this issue is quite controversially discussed in the
      literature. In this study, we used conventional biological evaluation methods and
      atomic force microscopy (AFM) to compare the effects of SWCNTs on three different
      cell types: bovine articular chondrocytes, human bone marrow-derived mesenchymal
      stem cells and HeLa cells. No obvious effects of SWCNTs on cell morphology and
      viability were observed during 3 days in vitro culture. However, SWCNTs
      significantly increased the Young's modulus of all the three types of cells. The
      effect of SWCNTs on Young's modulus was in an increasing order of Hela cells <
      chondrocytes < mesenchymal stem cells. AFM was shown to be a useful tool for
      investigation of the effect of nanomaterials on mechanical property of cells.

PMID- 24734518
TI  - Bone marrow stromal cell adhesion and morphology on micro- and sub-micropatterned
      titanium.
AB  - The objective of this study was to investigate the adhesion and morphology of
      bone marrow derived stromal cells (BMSCs) on bulk titanium (Ti) substrates with
      precisely-patterned surfaces consisting of groove-based gratings with groove
      widths ranging from 50 micro m down to 0.5 micro m (500 nm). Although it is well
      known that certain surface patterning enhances osteoblast (bone-forming cell)
      functions, past studies on cell-pattern interactions reported in the literature
      have heavily relied on surface patterning on materials with limited clinical
      relevance for orthopedic applications, such as polymeric substrates. The clinical
      need for improving osseointegration and juxtaposed bone formation around load
      bearing Ti implants motivated this in vitro study. BMSCs were selected as model
      cells due to their important role in bone regeneration. The results showed
      significantly greater BMSC adhesion density and more favorable cell morphology on
      sub-micropatterned gratings when compared with larger micropatterned gratings and
      non-patterned control surfaces after both 24 hr and 72 hr cultures. We observed
      increasing cellular alignment and elongation with decreasing feature size. We
      also identified two distinctive cellular morphologies: Type I-Attached and spread
      cells that elongated along the pattern axes; and Type II-Superficially adhered
      round cells. Sub-micropatterned gratings demonstrated significantly greater Type
      I cell density than the non-patterned control, and lower Type II cell density
      than the larger micropatterned gratings. Collectively, these results suggest
      potential for rationally designing nano-scale surface topography on Ti implants
      to improve osseointegration.

PMID- 24734519
TI  - The cellular uptake and cytotoxic effect of silver nanoparticles on chronic
      myeloid leukemia cells.
AB  - Several studies have suggested that silver nanoparticles (AgNPs) have the
      potential to treat human cancers, including leukemia. However, the detailed
      cellular mechanisms for AgNPs to inhibit the growth of leukemic cells and their
      efficacy on clinical isolates of leukemic patients are not elucidated. In this
      study, the cellular uptake and cytotoxic mechanism of AgNPs in chronic myeloid
      leukemia (CML) cells were investigated. AgNPs were synthesized with a modified
      polyol method, which were stable under cell culture conditions with fetal bovine
      serum (FBS). AgNPs were demonstrated to be able to enter K562 cells (a CML cell
      line) in a dose-dependent manner and locate in endosomes. Reactive oxygen species
      (ROS) could be generated upon AgNPs exposure and cause cytotoxicity and
      apoptosis. It was also found that AgNPs treatment inhibited the viability of
      cells from CML patients (n = 4). The cell cycle status and several critical
      regulators were altered upon AgNPs treatment as well. All these cellular and
      molecular alterations caused by AgNPs exposure could be reversed by the addition
      of Vitamin C (an antioxidant). These results suggested that proper usage of AgNPs
      would be of great significance for CML treatment in future.

PMID- 24734520
TI  - Cellular uptake and photosensitizing properties of quantum dot-chlorin e6
      complex: in vitro study.
AB  - Recently it has been suggested that quantum dots could be used in the
      photodynamic therapy of cancer as resonant energy donors for conventional
      porphyrin type photosensitizers. Here we summarize our results obtained by
      studying a non-covalent complex formed between quantum dots and a second
      generation photosensitizer, chlorin e6, in aqueous medium and in live pancreatic
      MiaPaCa2 cancer cells. Spectral changes in the absorption and photoluminescence
      of quantum dots and chlorin e6, as well as changes in the photoluminescence
      lifetime of quantum dots, revealed the formation of quantum dot-chlorin e6
      complex. Fluorescence confocal microscopy with spectral imaging unit showed
      uptake of quantum dot-chlorin e6 complex in live cancer cells: the complex
      localized in plasma membrane and endocytic vesicles. Fluorescence lifetime
      imaging revealed Forster resonance energy transfer from quantum dots to chlorin
      e6 within live cells. Finally, a light-induced damage to cancer cells by the
      quantum dot-chlorin e6 complex was achieved.

PMID- 24734521
TI  - Comparative evaluation of polymeric nanoparticles of rifampicin comprising
      Gantrez and poly(ethylene sebacate) on pharmacokinetics, biodistribution and lung
      uptake following oral administration.
AB  - The present study reports the comparative pharmacokinetic evaluation and
      biodistribution of rifampicin (RIF) following oral administration of
      nanoparticles of a bioadhesive polymer, Gantrez and a hydrophobic polymer
      poly(ethylene sebacate) (PES). A specific objective of the study was to evaluate
      lung uptake of the nanoparticles following oral administration. Nanoparticles
      were obtained in the size range 350-450 nm with rifampicin loading of 12-14% w/w.
      Zeta potential confirmed colloidal stability. PES nanoparticles revealed high
      macrophage uptake compared to Gantrez nanoparticles, and direct correlation was
      observed between hydrophobicity (contact angle) and macrophage uptake (r2 
      0.940). Enhanced RIF uptake with folic acid anchoring suggested folate receptor
      mediated uptake. RIF nanoparticles exhibited significantly higher Cmax and AUC,
      delayed Tmax and sustained release compared to plain RIF. More importantly the
      plasma concentration of RIF with the nanoparticles was significantly greater than
      the MIC of RIF (0.25 microng/mL) over 24 h. While gamma scintigraphy revealed
      higher lung accumulation of nanoparticles, the concentration with Gantrez
      nanoparticles was significantly higher. HPLC evaluation of lung concentration
      correlated with scintigraphy data. The significantly higher bioavailability and
      lung accumulation with Gantrez nanoparticle over PES nanoparticles was attributed
      mucoadhesion and high affinity of Gantrez to the Peyer's patches. Our study
      suggests Gantrez nanoparticles as a promising carrier for enhancing lung
      accumulation of drugs.

PMID- 24734522
TI  - Inhibitory effect of biosynthetic nanoscale peptide Melittin on hepatocellular
      carcinoma, driven by survivin promoter.
AB  - Hepatic resection and orthotopic liver transplantation are the only potentially
      curative treatments for hepatocellular carcinoma (HCC) but are indicated only in
      a minority of patients. Biosynthetic nanoscale peptide Melittin (Mel) is
      postulated to disrupt microbial phospholipid membranes by formation of stable or
      transient pores. Survivin, a member of the inhibitor of apoptosis family, is
      transcriptionally upregulated in most malignant tissues but not in normal
      tissues. It has been reported that the survivin promoter activity is tumor
      specific and makes it a good candidate for construction of gene therapy vectors.
      In the present study, a non-viral vector (pSURV-Mel), encoding Mel gene, was
      developed to evaluate its anti-tumor effect in HCC cell lines and in vivo in a
      mouse model of human HCC xenograft tumor. Our results showed that the survivin
      promoter is specifically activated in tumor cells, and the pSURV-Mel plasmid
      expressed Mel selectively in tumor cells and also induced cytotoxicity. Moreover,
      intratumoral Injection of pSURV-Mel significantly suppressed the growth of
      xenograft tumors. Mechanistically, pSURV-Mel induced cell death by an apoptosis
      dependent pathway. All taken together, this study elucidates a relatively safe,
      highly effective and cancer specific gene therapy strategy for HCC. The
      mechanisms of non-viral vector-induced cell death which were revealed by this
      work will shed light on the construction of more powerful vectors for cancer
      therapy.

PMID- 24734523
TI  - Differential toxicity of rod and spherical zinc oxide nanoparticles on human
      peripheral blood mononuclear cells.
AB  - The cytotoxic and genotoxic potential of rod and spherical zinc oxide
      nanoparticles (ZnO NPs) were evaluated on human peripheral blood mononuclear
      cells (PBMCs). Their sizes and shapes were determined by Transmission electron
      microscopy (TEM) and physical characterizations were done by X-ray diffraction
      (XRD) and Dynamic light scattering (DLS). The cytotoxic potential of rod ZnO NPs
      was greater than spherical ZnO NPs when applied to PBMCs and was limited to the
      proliferative lymphocytes. Rod ZnO NPs produced more reactive oxygen species
      (ROS) compared to spherical ones. Additionally rod ZnO NPs induced significant
      DNA damage to PBMCs as revealed by cytokinesis block micronucleus (CBMN) assay
      and comet assay. On the other hand UV absorption property was enhanced in case of
      spherical ZnO NPs compared to rod ZnO NPs. Thus, present study implicates the
      shape dependent differential application of ZnO NPs in our daily life.

PMID- 24734524
TI  - Enhancing proteasome-lnhibitor effect by functionalized gold nanoparticles.
AB  - Colloidal gold nanoparticles intensify the anticancer response of the drug
      bortezomib, a proteasome inhibitor. Polyethylene glycol-coated gold nanoparticles
      and the drug show a synergistic effect in reducing the cell viability of prostate
      cancer cell line Du145. It was observed a significant cell viability reduction
      with bortezomib concentrations as low as 4 nM. The proteasome inhibitor alone had
      to be present at concentrations in the ranger of 120 nM to induce identical
      cytotoxicity response. These findings demonstrate that gold nanoparticles
      enhancing the permeation and retention (EPR) effect in Du145 cells and open the
      possibility to decrease multi-drug resistance (MDR). The in vitro results of
      functionalized gold nanoparticles, internalized by cancer cells, pave the way for
      a more efficient proteasome inhibitor delivery and release in adenocarcinoma
      cells.

PMID- 24734525
TI  - Multifunctional carbon nanotube/bioceramics modulate the directional growth and
      activity of osteoblastic cells.
AB  - Biomaterials can still be reinvented to become simple and universal bone
      regeneration solutions. Following this roadmap, a bone graft of carbon nanotube
      (CNT)/glass/hydroxyapatite (HA) with controlled CNT agglomeration state was
      designed with multifunctionalities able to stimulate the bone cell phenotype. The
      preparation route, the mechanical and electrical behavior and the in vitro
      profiles of degradation and osteocompatibility were described. A non-destructive
      dynamic route was found to have a higher influence than the Diels-Alder
      functionalization one on controlling the CNT agglomerate state in the ceramic
      matrix composite. Biologically safe CNT agglomerates, with diameter sizes below 3
      microm homogenously distributed, were obtained in non-functionalized and
      functionalized composites. Yet, the lowest CNT damage and the highest mechanical
      and electrical properties were found for the non-functionalized materials. Even
      though that these composites present higher degradation rate at pH:3 than the
      ceramic matrix, the CNT agglomerates are released with safe diameter sizes. Also,
      non-functionalized composites allowed cellular adhesion and modulated the
      orientation of the cell growth, with a proliferation/differentiation relationship
      favoring osteoblastic functional activity. Findings offer further contributions
      for bone tissue engineering by showing that multifunctional bone grafts with high
      electroconductivity, and integrating CNT agglomerates with maximized interfacing
      area, allow the in situ control of bone cell functions.

PMID- 24734526
TI  - Nanostructured sensors containing immobilized nuclear receptors for thyroid
      hormone detection.
AB  - Thyroid hormone receptors (TRs) are members of the nuclear receptors (NRs)
      superfamily, being encoded by two genes: TRa and TRbeta. In this paper, the
      ligand-binding domain (LBD) of the TRbeta1 isoform was immobilized on the surface
      of nanostructured electrodes for TR detection. The platforms containing TRbeta1
      LBD were applied to the detection of specific ligand agonists, including the
      natural hormones T3 (triiodothyronine) and T4 (thyroxine), and the synthetic
      agonists TRIAC (3,5,3'-triiodothyroacetic acid) and GC-1 [3,5-dimethyl-4-(4'
      hydroxy-3'-isopropylbenzyl phenoxy) acetic acid]. Detection was performed via
      impedance spectroscopy. The biosensors were capable of distinguishing between the
      thyroid hormones T3 and T4, and/or the analogues TRIAC and GC-1 at concentrations
      as low as 50 nM. The detection and separation of thyroid hormones and analogue
      ligands by impedance techniques represents an innovative tool in the field of
      nanomedicine because it allows the design of inexpensive devices for the rapid
      and real-time detection of distinct ligand/receptor systems.

PMID- 24734527
TI  - Sequencing-by-ligation using oligonucleotide probes with 3'-thio-deoxyinosine.
AB  - We have developed a novel sequencing-by-ligation (SBL) system employing
      oligonucleotide probes containing 3'-thio-deoxyinosine on a microarray. The
      oligonucleotide probes were synthesized from 3'-S-(2-cyanoethyl-N,N
      diisopropylphosphorothioamidite)-5'-O-(4,4' dimet-hoxytrityl) deoxyinosine. The
      resultant probes could be cleaved chemically by aqueous silver ions under mild
      conditions, generating a 5'-terminal phosphate group in a degradation
      oligodeoxynucleotide fragment. This 5'-terminal phosphate was used directly for
      detecting the corresponding bases in subsequent sequencing cycles. The queried
      bases in the template were identified with eight cycles of ligation and cleavage.
      The read length of our method could reach up to 40 bp with high accuracy. As this
      SBL method uses commercially available enzymes and standard microarrays, it will
      be amenable to automation and adaptation by the research community.

PMID- 24734528
TI  - Convenient generation of quantum dot-incorporated photonic crystal beads for
      multiplex bioassays.
AB  - Barcode particles have a demonstrated value for multiplexed bioassays in clinical
      diagnostics, drug discovery, and so on. Attempts to develop this technology are
      focusing on the generation of novel particles with a large number of
      identifications to increase the throughput of the assays. Here we report a new
      type of barcode particles with quantum dot (QD)-photonic crystal (PC) joint
      spectrum encoding. These barcode particles are simply prepared by in-situ
      polymerization of CdTe QDs-contained acrylamide pre-gel in the colloidal photonic
      crystal beads (PCBs). By encapsulating different wavelength-and-intensity QDs
      into the PCBs with various-reflection spectra, thousands of available barcode
      particles could be obtained. Moreover, by employing magnetic nanoparticles into
      the PCBs, the achieved barcode particles could be conferred a function of
      controllable movement under magnetic field. This feature could significantly
      increase the sensitivity and simplify the processing of the bioassays.

PMID- 24734529
TI  - A transparent nanostructured optical biosensor.
AB  - Herein we report a new transparent nanostructured Fabry-Perot interferometer
      (FPI) device. The unique features of the nanostructured optical device can be
      summarized as the following: (i) optically transparent nanostructured optical
      device; (ii) simple and inexpensive for fabrication; (iii) easy to be fabricated
      and scaled up as an arrayed format. These features overcome the existing barriers
      for the current nanopore-based interferometric optical biosensors by measuring
      the transmitted optical signals rather than the reflected optical signals,
      thereby facilitating the optical testing significantly for the arrayed biosensors
      and thus paving the way for their potential for high throughput biodetection
      applications. The optically transparent nanostructures (i.e., anodic aluminum
      oxide nanopores) inside the FPI devices are fabricated from 2.2 microm thick
      lithographically patterned Al thin film on an indium tin oxide (ITO) glass
      substrate using a two-step anodization process. Utilizing the binding between
      Protein A and porcine immunoglobulin G (IgG) as a model, the detection of the
      bioreaction between biomolecules has been demonstrated successfully. Experiments
      found that the lowest detection concentration of proteins is in the range of
      picomolar level using current devices, which can be easily tuned into the range
      of femtomolar level by optimizing the performance of devices.

PMID- 24734530
TI  - Surface properties of quantum dots define their cellular endocytic routes,
      mitogenic stimulation and suppression of cell migration.
AB  - The practical use of quantum dots (QD) as diagnostic, visualizing and therapeutic
      nano-agents depends on the understanding of fundamental mechanisms of their
      entrance and trafficking within cells. Here we show that CdSe/ZnS carboxylic
      coated QD (COOH-QD) enter fibroblast cells via lipid raft/caveolin-mediated
      endocytosis, pass early sorting endosomes and accumulate in the multivesicular
      bodies, but not in the lysosomes. Later phase of their endocytosis leads to the
      generation of lipid raft/caveolin-dependent endocytosis inhibition that prevents
      intracellular uptake of new COOH-QD, but not the QD coupled with platelet-derived
      growth factor BB (PDGF-QD). PDGF-QD enter fibroblasts by the clathrin-mediated
      endocytosis and undergo similar intracellular trafficking as COOH-QD, yet they
      accumulate in lysosomes in contrast to COOH-QD. The PDGF-QD activate PDGF
      receptor-beta and are mitogenic, however, COOH-QD suppress cell migration and
      chemotaxis. Data show that surface coating of QD with the biologically active
      proteins redirects their intracellular traffic routes and changes their
      biological activity.

PMID- 24734531
TI  - On the mucoadhesive properties of chitosan-coated polycaprolactone nanoparticles
      loaded with curcumin using quartz crystal microbalance with dissipation
      monitoring.
AB  - Quartz Crystal Microbalance with Dissipation Monitoring (QCM-D) was used to
      investigate the mucoadhesive properties of nanoparticles decorated with low,
      medium and high molar mass chitosan (CS). Uncoated and chitosan-coated
      polycaprolactone (PCL) nanoparticles loaded with curcumin were prepared by
      nanoprecipitation method and characterized in terms of size, surface charge and
      drug content. The interactions between nanoparticles and mucin layer were
      monitored after the treatment of SAM-functionalized gold-coated quartz crystals
      with bovine submaxillary gland mucin (BSM). The results show that all
      investigated chitosan-coated nanoparticles adsorb onto the BSM layer, and the
      mass uptake was found to be independent of the chitosan molar mass. Uncoated
      nanoparticles showed, however, no affinity with BSM layer, confirming that the
      adsorption of colloidal systems occurs due to their decoration with chitosan. The
      adhesion is mainly attributed to electrostatic interactions between protonated
      amino groups of mucoadhesive chitosan and negatively charged groups of mucin. The
      results suggest that chitosan-coated nanoparticles are promising carriers for
      hydrophobic drugs delivery in the buccal mucosa.

PMID- 24734532
TI  - Three monofunctional copolymers into one multifunctional Micelle: Part 1.
      Preparation and properties.
AB  - In the present work, we propose a new multifunctional micelle, co-self-assembled
      from different monofunctional copolymers, for tumor targeting and fluorescent and
      electron spin resonance (ESR) dual detection. Firstly, a poly(D,L-lactic acid)-b
      poly(N-isopropyl methacrylamide-co-N-isopropylmaelic acid-co-10-undecenoic acid)
      b-poly(N-acryloxysuccinimide) (PLA-PNNUA-PNAS) copolymer, with pH-dependent
      thermo-responsive properties, was synthesized. The copolymer was synthesized
      using reversible addition fragmentation chain transfer (RAFT) polymerization
      method, after which it was further used as a parent copolymer to combine with
      folic acid (FA), fluorescein isothiocyanate (FITC) and 4-amino-2,2,6,6
      tetramethylpiperidin-1-oxyl (4-NH2-TEMPO), respectively, resulting into three new
      monofunctional copolymers. Finally, the multifunctional copolymer micelle was
      easily then fabricated, through co-self-assembly, using the monofunctional
      copolymers. The results from in vitro cell assays indicated that the proposed
      micelle was able to provide desired multifunctional properties, including tumor
      specific targeting and fluorescent and ESR dual detection. Additionally, the
      parent copolymer allowed conjugation with other ligands to prepare them for more
      functional copolymers attachment for future potential applications. More
      importantly, the multifunctional properties of the copolymer micelles could be
      rationally tailored, able for given purposes.

PMID- 24734533
TI  - Novel layer-by-layer structured nanofibrous mats coated by protein films for
      dermal regeneration.
AB  - Layer-by-layer coating technique is effective in modifying the surface of
      nanofibrous mats, but overmuch film-coating makes the mats less porous to hardly
      suit the condition for tissue engineering. We developed novel nanofibrous mats
      layer-by-layer coated by silk fibroin and lysozyme on the cellulose electrospun
      template via electrostatic interaction. The film-coating assembled on the mats
      was not excessive because the charge of the proteins varied in the coating
      process due to different pH value. In addition, pure nature materials made the
      mats nontoxic, biodegradable and low-cost. The morphology and composition
      variation during layer-by-layer coating process was investigated and the results
      showed that the structure and thickness of film-coatings could be well
      controlled. The antibacterial assay and in vitro cell experiments indicated that
      the mats could actively inhibit bacteria and exhibit excellent biocompatibility.
      In vivo implant assay further verified the mats cultured with human epidermal
      cells could promote wound healing and avoid wound infection. Therefore, these
      mats showed promising prospects when performed for dermal reconstruction.

PMID- 24734534
TI  - Protein-polymer functionalized aqueous ferrofluids showing high T2 relaxivity.
AB  - Controlled size, shape and dispersibility of superparamagnetic iron oxide
      nanoparticles (SPIONs), has been achieved in a protein-polymer colloidal
      dispersion. Stable ferrofluid (FF) is synthesized in an aqueous medium of
      collagen, bovine serum albumin and poly(vinyl) alcohol that equilibrates with
      time, at ambient conditions, into an organized matrix with iron oxide particles
      sterically caged at defined sites. It mimics a biomineralization system; hence
      the process is termed biomimetics. Though the exact mechanism is not understood
      at this stage, we have established, with serial dilution of the protein-polymer
      solution that the SPIONs are formed inside the self-contained clusters of the two
      proteins and the polymer, which show a tendency to self assemble. More than the
      interparticle dipolar attractions of magnetic particles, electrostatic
      interactions play a role in cluster formation and collagen is responsible for the
      overall stability, supported by systematic dynamic light scattering data. The
      basic aim of this study was to increase magnetization of a previously synthesized
      ferrofluid without hampering stability, by reducing the total macromolecular
      concentration. Thrice the magnetization was achieved and in addition, the
      synthesized FFs exhibited very high transverse relaxivity and showed good
      contrast in mice liver, in the in vivo studies.

PMID- 24734535
TI  - Combined effect of polymeric nanocapsules and chitosan hydrogel on the increase
      of capsaicinoids adhesion to the skin surface.
AB  - This work explored the effect of the encapsulation in polymeric nanocapsules, as
      well as of the incorporation of such nanoparticles in a chitosan hydrogel, on the
      skin adhesion and skin penetration/permeation of capsaicinoids (capsaicin and
      dihydrocapsaicin), which are used as topical analgesic to treat chronic pain. The
      skin experiments were performed using a modified (drug adhesion and drug
      diffusion) and a normal Franz diffusion cell (drug diffusion) with porcine skin
      as membrane. The AUC0-h of the washability profile (% washed away vs. time)
      determined for the formulation combining both factors studied (chitosan hydrogel
      containing drug-loaded nanocapsules) was 198.88 +/- 10.05/153.53 +/- 5.99, for
      capsaicin and dihydrocapsaicin respectively, significantly lower than the values
      observed for the chitosan hydrogel containing free drug (291.57 +/- 3.83/278.18
      +/- 5.28) and for the hydroxyethyl cellulose containing drug-loaded nanocapsules
      (245.47 +/- 13.18/197.69 +/- 15.78). By adequate fitting to the monoexponential
      first order equation, the washing rate values indicated that the nanocapsules
      were more efficient in increasing the drugs skin adhesion than the chitosan gel.
      Regarding the skin penetration/permeation study, after washing the skin, the
      formulation which presented the lowest washing rate (chitosan gel containing
      nanocapsules) was the one which led to a higher amount of capsaicinoids in the
      skin layers (epidermis and dermis). Without washing the skin, the nanoencapsules
      caused retention of the drugs in the outer skin layer (epidermis). In conclusion,
      the skin adhesion of the nanocapsules and their capability of controlling the
      drug diffusion were shown. Combining chitosan gel to nanocapsules led to a
      formulation of great skin bioadhesion.

PMID- 24734536
TI  - Induction of osteogenic differentiation by nanostructured alumina surfaces.
AB  - Permanent orthopedic implants are becoming increasingly important due to the
      demographic development. Their optimal osseointegration is key in obtaining good
      secondary stability. For anchorage dependent cells, topographic features of a
      surface play an essential role for cell adhesion, proliferation, differentiation
      and biomineralization. We studied the topographical effect of nanostructured
      alumina surfaces prepared by chemical vapor deposition on osteogenic
      differentiation and growth of human osteoblasts. Chemical vapor deposition of the
      single source precursor (tBuOAIH2)2 led to synthesis of one dimensional alumina
      nanostructures of high purity with a controlled stoichiometry. We fabricated
      different topographic features by altering the distribution density of deposited
      one dimensional nanostructures. Although the topography differed, all surfaces
      exhibited identical surface chemistry, which is the key requirement for
      systematically studying the effect of the topography on cells. Forty-eight hours
      after seeding, cell density and cell area were not affected by the
      nanotopography, whereas metabolic activity was reduced and formation of actin
      fibres and focal adhesions was impaired compared to the uncoated control.
      Induction of osteogenic differentiation was demonstrated via up-regulation of
      alkaline phosphatase, bone sialoprotein, osteopontin and Runx2 at the mRNA level,
      demonstrating the potential of nanostructured surfaces to improve the
      osseointegration of permanent implants.

PMID- 24734537
TI  - Phosphatidylserine-targeted molecular imaging of tumor vasculature by magnetic
      resonance imaging.
AB  - Phosphatidylserine (PS), normally restricted to the inner leaflet of the plasma
      membrane, becomes exposed on the outer surface of viable endothelial cells in
      tumor vasculature, but not in normal blood vessels. In the present study, we
      report the use of PGN635, a novel human monoclonal antibody that specifically
      targets PS, for in vivo molecular MRI of tumor vasculature. The F(ab')2 fragments
      of PGN635 were conjugated to polyethylene glycol (PEG) coated iron oxide
      nanoparticles (IO). Targeting specificity of the PS-targeted Nanoprobe, IO
      PGN635F(ab')2 was first confirmed by in vitro MRI and histological staining. In
      vivo longitudinal MRI was then performed before and after i.v. injection of IO
      PGN635F(ab')2 into mice bearing 4T1 breast tumors. T2-weighted MR images at 9.4 T
      revealed inhomogeneous signal loss in tumor as early as 2 h post injection.
      Furthermore, ionizing radiation induced a significant increase in PS exposure on
      tumor vascular endothelial cells, resulting in significantly enhanced and
      sustained tumor contrast (p < 0.05). Spatially heterogeneous MRI contrast
      correlated well with histological staining of tumor vascular endothelium. Our
      studies suggest that PS exposed within the lumen of tumor vasculature is a highly
      specific and useful biomarker for targeted MRI contrast agents.

PMID- 24734538
TI  - In vivo imaging of infection using a bacteria-targeting optical nanoprobe.
AB  - Wound and device-associated infection is a leading cause for morbidity and
      mortality. As such, rapid and early diagnosis of bacterial colonization is
      critical to infection treatment. The current diagnostic methods however, are not
      able to meet this requirement. Therefore, there is a practical need for the
      development of a new method to rapidly identify colonized bacteria. This study
      aims to develop optical nanoprobes that can detect and quantify the number of
      colonized bacteria in real time. To this end, we have synthesized an imaging
      nanoprobe with three elements: Concanavalin A (Con A) as a bacterial targeting
      ligand, a nanoparticle carrier, and a near infrared fluorescent dye. An MTS assay
      revealed that the bacteria nanoprobe is cell compatible. In vitro testing further
      showed that the bacteria nanoprobe had a very high specificity and affinity to
      bacteria. Using a murine wound and catheter infection model, we found that the
      bacteria nanoprobes can rapidly detect and quantify the extent of bacterial
      colonization on wounds and catheters in real time.

PMID- 24734539
TI  - Synthesis and anti-staphylococcal activity of TiO2 nanoparticles and nanowires in
      ex vivo porcine skin model.
AB  - Staphylococcus aureus is one of the major causes of skin and soft tissue
      infections. In this study we compared the antimicrobial activity of two different
      TiO2 nanoformulations against Staphylococcus aureus. We synthesized TiO2
      nanoparticles of approximately 80 nm diameter and TiO2 nanowires of approximately
      100 nm diameter. Both nanoformulations possess anti-microbial activity; were non
      hemolytic and cytocompatible. However, the anti-staphylococcal activity of TiO2
      nanowires was better than the nanoparticles. In broth culture, growth of S.
      aureus was only partially inhibited by 2% and 4 wt% TiO2 nanoparticles and
      completely inhibited by TiO2 nanowires till 24 h. TiO2 nanowires treated S.
      aureus cells exhibits diminished membrane potential than nanoparticle treated
      cells. The anti-microbial properties of both TiO2 nanoformulations were validated
      using ex vivo porcine skin model which supplements the in vitro assays. Anti
      bacterial activity of the TiO2 nanowires were also validated against multi drug
      resistant pathogenic strains of S. aureus, showing the clinical potency of the
      TiO2 nanowires compared to its nanoparticles.

PMID- 24734540
TI  - A simplified method to attach antibodies on liposomes by biotin-streptavidin
      affinity for rapid and economical screening of targeted liposomes.
AB  - The biotin-Streptavidin (STREP) technique for attachment of monoclonal antibodies
      (mAbs) (or other ligand types) on liposome surface offers high attachment yield,
      however it is time consuming and expensive due to the number of steps used and
      the consumption of large quantities of STREP. Herein, a simplified, fast and
      economic technique, by incubating pre-mixed biotin-mAb/STREP with biotin
      liposomes, at a 3:1:1 biotin-mAb/STREP/biotin-LIP ratio (mol/mol/mol) was
      evaluated. The physichochemical properties, final mAb attachment yield and
      targeting potential of liposomes decorated with an anti-transferrin receptor mAb
      (TfR-mAb), prepared by the simple method (SM) and the conventional method (CM),
      were compared. The vesicle uptake by hCMEC/D3 cells (known to overexpress TfR)
      were considered as a measure of liposome targeting capability. Results show that
      both targeted liposome types (SM and CM) have small size (mean diameters around
      150 nm), low poly-dispersity (approx. 0.20) and similar mAb attachment yield
      (between 64-88%). However, the uptake of the SM-liposomes is slightly lower
      compared to CM-LIP (24-30% decrease), suggesting that the modulated conformation
      of mAbs on the liposome surface (triplets attached to one single STREP molecule)
      results in decreased targeting capability. Nevertheless, the simpler and faster
      one-step preparation procedure which has very high lipid recovery (> 95%)
      compared to the CM (50-60%) and 15-30 times lower consumption of STREP, may be a
      good alternative for initial screening of various mAbs as ligands for targeted
      liposomal or other nanotechnologies, during pre-clinical development.

PMID- 24734541
TI  - Nanoformulation improves activity of the (pre)clinical anticancer ruthenium
      complex KP1019.
AB  - Ruthenium anticancer drugs belong to the most promising non-platinum anticancer
      metal compounds in clinical evaluation. However, although the clinical results
      are promising regarding both activity and very low adverse effects, the clinical
      application is currently hampered by the limited solubility and stability of the
      drug in aqueous solution. Here, we present a new nanoparticle formulation based
      on polymer-based micelles loaded with the anticancer lead ruthenium compound
      KP1019. Nanoprepared KP1019 was characterised by enhanced stability in aqueous
      solutions. Moreover, the nanoparticle formulation facilitated cellular
      accumulation of KP1019 (determined by ICP-MS measurements) resulting in
      significantly lowered IC50 values. With regard to the mode of action, increased
      cell cycle arrest in G2/M phase (PI-staining), DNA damage (Comet assay) as well
      as enhanced levels of apoptotic cell death (caspase 7 and PARP cleavage) were
      found in HCT116 cells treated with the new nanoformulation of KP1019.
      Summarizing, we present for the first time evidence that nanoformulation is a
      feasible strategy for improving the stability as well as activity of experimental
      anticancer ruthenium compounds.

PMID- 24734542
TI  - Fullerene-C60 derivatives prevent UV-irradiation/ TiO2-induced cytotoxicity on
      keratinocytes and 3D-skin tissues through antioxidant actions.
AB  - Microcorpuscular titanium dioxide (TiO2), a useful sunscreen agent,
      photocatalyzes generation of reactive oxygen species (ROS). We assessed
      protective effects of fullerene-C60 derivatives or microcolloidal platinum (Pt)
      against ultraviolet ray (UV)-irradiation in the presence of TiO2 in vitro. UV
      irradiation (8 J/cm2, mixed UVA and UVB) in the presence of 15 ppm TiO2 on HaCaT
      keratinocytes decreased cell viability as quantified by WST-1 assay, and
      increased both intracellular ROS and cell-membrane-lipid peroxidation, as
      quantified by nitroblue-tetrazolium (NBT) assay and diphenyl-1-pyrenylphosphine
      (DPPP) assay, respectively, whereas all of three phototoxicity-related symptoms
      were appreciably repressed almost to UV-unirradiational levels by pretreatment
      with polyvinylpyrrolidone-entrapped fullerene-C60 (C60/PVP) or fullerene-C60
      dissolved in squalane (C60/Sqn) in a dose-dependent manner of C60, but scarcely
      by PVP alone or Sqn alone. In contrast, Pt repressed intracellular ROS
      generation, but did not prevent either peroxidation of cell-membrane-lipid or
      cell mortality. Then in the epidermis of 3-dimensional human skin tissue model,
      UV-irradiation in the presence of TiO2 extensively induced two symptoms such as
      ROS-generation around perinuclear regions and membrane-lipid peroxidation, both
      of which were repressed by C60/PVP or C60/Sqn, whereas Pt did not prevent
      membrane-lipid peroxidation adequately. Thus the advantageous application of the
      lipophilic antioxidant fullerene-C60 which effectively protects cell membrane
      against peroxidation. In conclusion, fullerene-C60 can be expected to serve as an
      antioxidant for scavenging of TiO2-photocatalyzed ROS in the skin surface, and
      therefore provide a functional improvement of TiO2-containing sunscreens.

PMID- 24734543
TI  - Mechanism of cellular uptake, localization and cytotoxicity of organic
      nanoparticles.
AB  - Water-dispersed organic nanoparticles (NPs) were prepared from a conjugated
      molecule 2,5,2',5'-tetra(4'-N,N-diphenylaminostyryl)biphenyl (DPA-TSB). As a
      potential material for photodynamic therapy, we investigated cellular toxicity by
      using fluorescence confocal microscopy and Western blotting. Our results
      demonstrated that the cells treated with DPA-TSB NPs showed an increase in
      apoptosis accompanied by the increased expression of Bax protein, decreased
      expression of Bcl-2 protein and caspase-3 protein, the decreased mitochondrial
      membrane potential and the release of ROS. Using inhibitors of endocytosis can
      block nanoparticles uptake, indicating that DPA-TSB NPs entered the cells via an
      energy-dependent manner, mostly through clathrin-mediated and caveolae-mediated
      processes.

PMID- 24734544
TI  - The luminescent properties and toxicity controllability investigation of novel
      ZnO quantum dots with Schiff base complexes modification.
AB  - The Schiff base complexes modified ZnO quantum dots (ZnO-SBC QDs) are
      successfully synthesized via the reflux and chemical co-precipitation route. For
      control experiments, we also synthesized the ZnO QDs and amino-modified ZnO QDs
      (ZnO-NH2 QDs). The structures and morphologies of the samples were characterized
      via X-ray powder diffraction (XRD), transmission electron microscopy (TEM), high
      resolution transmission electron microscopy (HR-TEM), FTIR spectroscopy (IR),
      Fluorescence Spectrometer (FL) and so on. The XRD pattern shows that the three
      types of QDs possess hexagonal wurtzite structures. The TEM investigation reveals
      that the as-prepared products have hexagonal morphologies. The plane fringe with
      0.26 nm crystalline plane spacing of three types of quantum dots is assigned to
      the ZnO {002} planes via HR-TEM, which match with the lattice parameter of the
      hexagonal wurtzite structure of ZnO and also coincide with the data obtained by
      XRD. By analyzing the fluorescence emission and excitation spectra of ZnO QDs,
      ZnO-NH2 QDs, ZnO-SBC QDs and Schiff base complexes, we find that the ZnO-SBC QDs
      still have a perfect fluorescence emission which makes it interesting candidates
      for luminescence applications such as biochemical sensors and fluorescent labels
      to mark the cells and DNA. This novel ZnO-SBC QDs under UV irradiation is capable
      of generating reactive oxygen species by UV irradiation and may be used for the
      photodynamic therapy. The surface modification with Schiff base complexes makes
      it difficult to release Zn2+, therefore the toxicity is much more controllable.

PMID- 24734545
TI  - Synthesis, biodistribution, and imaging of PEGylated-acetylated polyamidoamine
      dendrimers.
AB  - Polyamidoamine (PAMAM) dendrimers have been widely used as drug carriers, non
      viral gene vectors and imaging agents. However, the use of dendrimers in
      biological system is constrained because of inherent toxicity and organ
      accumulation. In this study, the strategy of acetylation and PEGylation
      acetylation was used to minimize PAMAM dendrimers toxicities and to improve their
      biodistribution and pharmacokinetics for medical application. PEGylated
      acetylated PAMAM (G4-Ac-PEG) dendrimers were synthesized by PEGylation of
      acetylated PAMAM dendrimer of generation 4 (G4) with acetic anhydride and
      polyethylene glycol (PEG) 3.4 k. To investigate the cytotoxicity and in vivo
      biodistribution of the conjugates, in vitro cell viability analysis, Iodine-125
      (125I) imaging, tissue distribution and hematoxylin-eosin (HE) staining were
      performed. We find that acetylation and PEGylation-acetylation essentially
      eliminates the inherent dendrimer cytotoxicity in vitro. Planar gamma (gamma)
      camera imaging revealed that all the conjugates were slowly eliminated from the
      body, and higher abdominal accumulation of acetylation PAMAM dendrimer was
      observed. Tissue distribution analysis showed that PEGylated-acetylated
      dendrimers have longer blood retention and lower accumulation in organs such as
      the kidney and liver than the non-PEGylated-acetylated dendrimers, but
      acetylation only can significantly increase the accumulation of G4 in the kidney
      and decrease the concentration in blood. Histology results reveal that no obvious
      damage was observed in all groups after high dose administration. This study
      indicates that PEGylation-acetylation could improve the blood retention, decrease
      organ accumulation, and improve pharmacokinetic profile, which suggests that
      PEGylation-acetylation provides an alternative method for PAMAM dendrimers
      modification.

PMID- 24734546
TI  - Biodistribution of quantum dots in the kidney after intravenous injection.
AB  - The biodistribution of nanoparticles is a major subject of current nanomedical
      research. To date, however, the exact investigation of nanoparticle fate in the
      microenvironment of a main excretory organ, the kidney has largely been
      neglected. In this study, the biodistribution of polyethylene glycol-coated
      quantum dots (Qdots) with special focus on their interaction with the kidney is
      investigated. Upon intravenous injection, nanoparticles showed effective blood
      circulation in mice and significant renal accumulation after two hours.
      Histological analysis of the kidney revealed that Qdots were strongly associated
      to the intraglomerular mesangial cells. This preferential deposition of
      nanoparticles in the kidney mesangium is highly promising, since it could be of
      utmost value for site-specific treatment of severe kidney diseases like diabetic
      nephropathy in the future.

PMID- 24734547
TI  - Fluorescence plate reader for quantum dot-protein bioconjugation analysis.
AB  - We present here a new and alternative method that uses a Fluorescence Plate
      Reader in a different approach, not to study protein-protein interactions, but to
      evaluate the efficiency of the protein bioconjugation to quantum dots (QDs). The
      method is based on the QDs' native fluorescence and was successfully tested by
      employing two different QDs-proteins conjugation methodologies, one by promoting
      covalent binding and other by inducing adsorption processes. For testing, we used
      bioconjugates between carboxyl coated CdTe QDs and bovine serum albumin,
      concanavalin A lectin and anti-A antibody. Flow cytometry and fluorescence
      spectroscopy studies corroborated the results found by the Fluorescence Plate
      Reader assay. This kind of analysis is important because poor bioconjugation
      efficiency leads to unsuccessful applications of the fluorescent bioconjugates.
      We believe that our method presents the possibility of performing semi
      quantitative and simultaneous analysis of different samples with accuracy taking
      the advantage of the high sensitivity of optical based measurements.

PMID- 24734548
TI  - Safety profile of dextran-spermine gene delivery vector in mouse lungs.
AB  - A nano-sized polymer, dextran-spermine (D-SPM), was shown to have the capacity to
      deliver gene to the lung of mouse via intranasal route. In this study,
      assessments on the safety profile of D-SPM were performed to complement the gene
      expression results. African green monkey kidney fibroblast (COS-7) and human
      adenocarcinoma breast (MCF-7) cells transfected with D-SPM/pDNA showed massive
      reduction in the number of viable cells. As for in vivo study, elevated level of
      neutrophils was observed, despite the minimal level of pro-inflammatory cytokines
      (TNF-alpha, IL-12, IFN-gamma) detected in the bronchoalveolar lavage fluid (BALF)
      of mice treated with the D-SPM/pDNA complexes. Histology profile examinations of
      the lungs showed mild inflammatory responses, with inflamed areas overlap with
      healthy areas. Although reduction of mice weight was seen at day 1 post
      administration, the mice did not show any sign of abnormal behavior or physical
      appearance. Biodistribution study was performed to determine the ability of the D
      SPM/pDNA complexes to infiltrate to other non-intended organs. The result showed
      that the D-SPM/pDNA complexes were only localized at the lung and no gene
      expression was detected in other organs or blood. In short, these results
      indicate that the D-SPM/pDNA exhibited mild toxicity in the mouse lungs.

PMID- 24734549
TI  - Magnetic beads-based chemiluminescent assay for ultrasensitive detection of
      pseudorabies virus.
AB  - A rapid, ultrasensitive and economical Pseudorabies virus (PRV) detection system
      based on magnetic beads (MBs) and chemiluminescence was developed in this paper.
      The carboxyl functionalized MBs (MBs-COOH) were covalently coupled with aminated
      DNA probes for capturing PRV biotinylated amplicon, the product of polymerase
      chain reaction (PCR). Agarose gel electrophoresis analysis approved the
      reliability of biotinylated amplicon. The MBs composites were incubated with
      alkaline phosphatase labeled streptavidin (ALP-SA) and chemiluminescene was
      determined by subsequently adding 3-(2'-spiroadamantane)-4-methoxy-4-(3"
      phosphoryloxy)phenyl-1,2-dioxetane (AMPPD). The optimal conditions of the PRV
      detection method were 10 microM for probe concentration, 50 degrees C for
      hybridization temperature and 30 min for hybridization time. The limit of
      detection (LOD) was as low as 100 amol/5 pM of amplicon which proved that this
      approach for PRV detection was ultrasensitive.

PMID- 24734550
TI  - Novel chitosan coated magnetic nanocarriers for the targeted Diclofenac delivery.
AB  - New magnetic devices consisting of magnetite functionalized with oleic acid and
      chitosan have been synthesized and employed to the loading of Diclofenac as
      potential tool for treatment of targeted inflammatory diseases. Magnetic loaded
      and un-loaded nanoparticles have been thoroughly characterized by infrared
      spectroscopy, transmission electron microscopy, determination of hydrodynamic
      diameter by Dynamic light scattering and zeta potential measurements at different
      pH conditions. A study of the release of Diclofenac has been performed in vitro
      and available mathematical models have been used to determine the release
      kinetic. Both properties and release data reveal that this nanomagnetic platform
      would be suitable for in vivo assays.

PMID- 24734551
TI  - Application of functional microsphere in human hepatitis B virus surface antigen
      detection.
AB  - A novel and simple emulsifier-free emulsion polymerization technique was
      developed for preparation of mono-dispersed amino functionalized polymer
      microspheres with well defined diameters (about 400 nm). Various characterization
      methods demonstrated that the obtained amino microspheres had a uniform size and
      good dispersity which were confirmed by scanning electron microscope (SEM). Zeta
      potential and Fourier transform infrared spectrometer (FT-IR) demonstrated that
      amino groups have been successfully introduced to the microsphere surface. These
      functionalized microspheres have been shown to be efficient and controllable
      carriers capable of immobilizing and enriching monoclonal antibodies. Moreover, a
      newest chemiluminescent enzyme-linked immunoassay (ELISA) approach has been
      developed for human Hepatitis B virus surface antigen (HBsAg) detection. HBsAg
      was sandwiched between goat anti-HBsAg polyclonal antibody and mouse anti-HBsAg
      antibody. Alkaline phosphatase (ALP) conjugated horse anti-mouse immunnogloblin
      was used to bond with monoclonal antibody. Finally, chemiluminesent (CL) signals
      were recorded after adding 3-(2-spiroadamantane)-4-methoxy-4-(3-phosphoryloxy)
      phenyl-1,2-dioxetane (AMPPD) which was used as a chemiluminescent substrate
      reagent of ALP. This novel chemiluminescent ELISA assay was proved to be of
      excellent specificity and high sensitivity when using ALP and AMPPD luminescence
      systems for specific HBsAg detection.

PMID- 24734552
TI  - Decrease of reactive oxygen species-related biomarkers in the tissue-mimic 3D
      spheroid culture of human lung cells exposed to zinc oxide nanoparticles.
AB  - Common 2-dimensional (2D) cell cultures do not adequately represent cell-cell and
      cell-matrix signaling and substantially different diffusion/transport pathways.
      To obtain tissue-mimic information on nanoparticle toxicity from in vitro cell
      tests, we used a 3-dimensional (3D) culture of human lung cells (A549) prepared
      with elastin-like peptides modified with an arginine-glycine-aspartate motif. The
      3D cells showed different cellular phenotypes, gene expression profiles, and
      functionalities compared to the 2D cultured cells. In gene array analysis, 3D
      cells displayed the induced extracellular matrix (ECM)-related biological
      functions such as cell-to-cell signaling and interaction, cellular function and
      maintenance, connective tissue development and function, molecular transport, and
      tissue morphology. Additionally, the expression of ECM-related molecules, such as
      laminin, fibronectin, and insulin-like growth factor binding protein 3 (IGFBP3),
      was simultaneously induced at both mRNA and protein levels. When 0.08-50
      microg/ml zinc oxide nanoparticles (ZnO-NPs) were administered to 2D and 3D
      cells, the cell proliferation was not significantly changed. The level of
      molecular markers for oxidative stress, such as superoxide dismutase (SOD), Bcl
      2, ATP synthase, and Complex IV (cytochrome C oxidase), was significantly reduced
      in 2D culture when exposed to 10 microg/ml ZnO-NPs, but no significant decrease
      was detected in 3D culture when exposed to the same concentration of ZnO-NPs. In
      conclusion, the tissue-mimic phenotype and functionality of 3D cells could be
      achieved through the elevated expression of ECM components. The 3D cells were
      expected to help to better predict the nanotoxicity of ZnO-NPs at tissue-level by
      increased cell-cell and cell-ECM adhesion and signaling. The tissue-mimic
      morphology would also be useful to simulate the diffusion/transport of the
      nanoparticles in vitro.

PMID- 24734553
TI  - Synthesis and properties of core-shell SiO2@Y2O3:Eu3+ wavelength conversion
      materials.
AB  - In this paper, with spherical SiO2 particles fabricated via Stober method,
      monodispersed and uniform SiO2 @Y2O3:Eu3+ core-shell submicrospheres were
      prepared through a simply homogeneous precipitation method. SEM, TEM and XRD
      analysis indicated that the as-prepared samples were uniform and well
      monodispersed spheres. The SiO2 core was perfectly coated by the shell composed
      of cubic crystalline Y2O3:Eu3+ and the thickness of the shell was about 26 nm.
      Photoluminescence spectra showed that the luminescence efficiency was improved
      remarkably after being coated on the SiO2 core. The 3D PL spectra showed that
      almost all UV photons in the range from 200 nm to 400 nm can be converted to
      visible photons by the as-prepared samples. Results showed that when the SiO2
      core was synthesized in the TEOS single feeding model with the amount of core
      being 0.4 g, doping concentration being 4% and annealing at 800 degrees C, the
      sample has the best performance on luminescence. By dispersing the as-prepared
      sample in the anti-reflection sol to prepared the wavelength conversion and anti
      reflection film and apply it to the silicon solar cell, the photoelectric
      conversion efficiency can be increased by 7.41% in maximum.

PMID- 24734554
TI  - Spectroscopic detection of clenbuterol applying gold nanoparticles encapsulated
      with melamine.
AB  - In this paper, a simple, rapid and highly sensitive method for detecting trace
      amount of clenbuterol based on gold nanoparticles (GNPs) encapsulated with
      melamine was investigated. Morphological characterization using SEM and AFM
      revealed that the size of obtained GNPs was about 15 nm. The hydrogen-bonding
      interaction existed between clenbuterol and melamine, which caused the
      aggregation of GNPs, was demonstrated by FT-IR and EELS spectrum. Consequently,
      the concentration of clenbuterol can be measured by the change of GNPs' color and
      optical absorption band with naked eye or absorption spectrum, respectively. A
      relationship existed between the intensity of the absorption band and
      concentration of clenbuterol. The possible impurities in practical applications
      such as alanine, MgCl2, tryptophan, NaCI, did not interfere in the detection of
      clenbuterol. The proposed protocol showed promising applications in the clinical
      and industrial detection of clenbuterol in food safety area.

PMID- 24734555
TI  - Hydrothermal synthesis and upconversion properties of CaF2:Er3+/Yb3+
      nanocrystals.
AB  - A series of rare-earth ions (Er3+ and Yb3+) Co-doped CaF2 upconversion
      luminescent nanomaterials have been successfully prepared via a facile
      hydrothermal method using pluronic p123 (p123), pluronic F127 (F127) and sodium
      citrate as surfactants at 180 degrees C with different reaction time. The
      crystallographic phase, size and morphology can be controlled by simply tuning
      the reaction parameters such as the types of surfactants and the reaction time.
      It is found that reaction time and surfactant play a key role in forming the
      nanocrystals with different morphologies. X-ray diffraction, field-emission
      scanning electron microscopy FE-SEM, and photoluminescence spectra were used to
      characterize the structure, morphology and upconversion luminescence properties
      of CaF2:Er3+/Yb3+ upconversion nanomaterials, respectively. The experimental
      results indicate that three monodispersive and highly uniform CaF2:Er3+/Yb3+
      nanocrystals with mean size of 200 nm, 3 um, and 700 nm have cubic and sphere
      shapes, respectively. While the possible mechanisms of upconversion luminescence
      are analyzed by the diagram of proposed energy transfer mechanisms, the schematic
      energy level diagrams showing typical upconversion processes for Er3+ also
      reveals that the as-synthesized CaF2:Er3+/Yb3 nanomaterials may be in the cubic
      structure with space group Fm-3m, in which Ln3+ cations occupy crystal lattice
      positions with lower point symmetry, leading to a high upconversion efficiency
      under the excitation of a 980 nm diode laser.

PMID- 24734556
TI  - The photoluminescent properties of Y2O3:Bi3+, Eu3+, Dy3+ phosphors for white
      light-emitting diodes.
AB  - Bi3+, Eu3+, Dy3+ activated Y2O3 phosphors were prepared through the sol-gel
      process. X-ray diffraction (XRD), Fourier transform infrared (FT-IR) spectra, and
      photoluminescence (PL) spectra were used to characterize the resulting phosphors.
      The XRD patterns show the refined crystal structure of Y2O3. The energy transfer
      processes of Bi(3+)-Eu3+ occurred in the host lattices. The thermal stability of
      Y2O3:Bi3+, Eu3+, Dy3+ phosphors was studied. Under short wavelength UV
      excitation, the phosphors show excellent characteristic red, blue, and yellow
      emission with medium intensity.

PMID- 24734557
TI  - Bio-functionalization of silicon carbide nanostructures for SiC nanowire-based
      sensors realization.
AB  - The bio-functionalization process consisting in grafting desoxyribo nucleic acid
      via aminopropyl-triethoxysilane is performed on several kinds of silicon carbide
      nanostructures. Prior, the organic layer is characterized on planar surface with
      fluorescence microscopy and X-ray photoelectron spectroscopy. Then, the
      functionalization is performed on two kinds of nanopillar arrays. One is composed
      of top-down SiC nanopillars with a wide pitch of 5 microm while the other one is
      a dense array (pitch: 200 nm) of core-shell Si-SiC nanowires obtained by
      carburization of silicon nanowires. Depending on both the pillar morphology and
      the pitch, different results in term of DNA surface coverages are obtained, as
      seen from fluorescence microscopy images. Particularly, in the case of the wide
      pitch array, it has been shown that the DNA molecules are located all along the
      nanopillars. To achieve a DNA sensor based on a nanowire-field effect transistor,
      the functionalization must be conducted on a single SiC nanowire or nanopillar
      that constitutes the channel of the field effect transistor. The localization of
      the functionalization in a small area around the nanostructures guarantees high
      performances to the sensor. In this aim, the functionalization process is
      combined with common microelectronics techniques of lithography and lift-off. The
      DNA immobilization is investigated by fluorescence microscopy and atomic force
      microscopy.

PMID- 24734558
TI  - The removal of metallic single-walled carbon nanotubes using an aqueous two-phase
      system.
AB  - Here we report our findings on the removal of metallic single-walled carbon
      nanotubes using an aqueous two-phase system. The aqueous two-phase system
      contained as received carbon nanotubes, polyethylene glycol, dextran, N
      methylpyrrolidone, cetyltrimethylammonium bromide, and water which phase
      separated into top and bottom phases. The top phase was dominated by polyethylene
      glycol whereas the bottom phase was dominated by dextran. The dextran-rich phase
      contained more semiconducting species while metallic species was more abundant in
      the polyethylene glycol rich-phase. It was found via Fourier-Transform Infrared
      Spectroscopy that cetyltrimethylammonium bromide only present in the dextran-rich
      phase. A selectivity mechanism is tentatively proposed and discussed.

PMID- 24734559
TI  - Simulation and analysis of terahertz modulator based a gated nanostructure.
AB  - In this paper we discuss the possibility of an electrically controlled terahertz
      modulator based on a gated two-dimensional electronic gas structure. To
      investigate and analyze the modulation capabilities of such a nanostructure, we
      calculated the modulation characteristics. Results caused by the change in
      intensity and phase of transmitted terahertz radiation are presented.

PMID- 24734560
TI  - Improved performance of P3HT:PCBM photovoltaic devices with ITO treated by
      hydrogen peroxide.
AB  - The properties of poly(3-hexylthiophene):(6,6)-phenyl C61 butyric acid methyl
      ester (P3HT:PCBM) organic photovoltaic devices (OPVs) with indium tin oxide (ITO)
      anode treated by hydrogen peroxide are investigated. The optimized hydrogen
      peroxide solution has a concentration of 10% and ITO is treated for 15 min. The
      modification of ITO anode results in an enhancement of the power conversion
      efficiency (PCE) of the device, which is attributed to the increase of the
      photocurrent. The performance enhancement is attributed to the work function
      modification of the ITO substrate through the strong oxygenation of hydrogen
      peroxide, and then the charge collection efficiency is improved.

PMID- 24734561
TI  - Synthesis of gold nanoparticles with graphene oxide.
AB  - Single sheets of functionalized graphene oxide are derived through chemical
      exfoliation of natural flake graphite. We present an effective synthetic method
      of graphene-gold nanoparticles hybrid nanocomposites. AFM (Atomic Force
      Microscope) was used to measure the thickness of the individual GO nanosheet.
      FTIR (Fourier transform infrared) spectroscopy was used to verify the attachment
      of oxygen functionalities on the surface of graphene oxide. TEM (Transmission
      Electron Microscope) data revealed the average diameters of the gold colloids and
      characterized the composite particles situation. Absorption spectroscopy showed
      that before and after synthesis the gold particle size did not change. Our
      studies indicate that the hybrid is potential substrates for catalysts and
      biosensors.

PMID- 24734562
TI  - Synthesis and properties of nano-polyaniline films doped with camphor sulfonic
      acid.
AB  - Polyaniline (PANI) is an important conductive polymer with good stability in the
      air and high conductivity. It can be used in the field of sensors, cells and
      capacitors. In this paper, PANI is prepared in the (NH4)2S2O8/HCI solution
      system. We used XRD, SEM and other relevant means to characterize the morphology
      and property of PANI-CSA, and we applied four-point probe measurement and FTIR to
      study the optical and electrical properties. We also analyzed the possible impact
      to infrared reflectance of various doping concentrations and the mechanism. The
      results show that the PANI-CSA film has the best performance and the highest
      infrared reflectivity when the doping ratio is 2:2.

PMID- 24734563
TI  - Preparation, electrochemical properties and electrocatalytic activity of Zn
      substituted tungstoborate modified electrode.
AB  - 3-Aminopropyltrimethoxysilane (APTMS) was covalently grafted on a glassy carbon
      electrode (GCE) by silicon-oxygen bonds formation. The APTMS-modified GCE was
      used as a suitable charged substrate to fabricate Keggin Zn-substituted
      tungstoborate (BW11Zn)-consisting monolayer film through layer-by-layer assembly
      based on the electrostatic attraction. This modification strategy is proven to be
      a general one suitable for anchoring many kinds of POMs on the APTMS-modified
      GCE. The APTMS/BW11Zn film obtained on GCE is electrochemically active in acid
      aqueous solutions and exhibited three pairs of well defined, stable and quasi
      reversible cyclic voltammetry peaks in the pH range 0-2. The anodic and cathodic
      peak currents are linearly proportional to the scan rate in the 200-1000 mV s(
      1), indicating a surface confined electrode process. The formal potentials of
      BW11Zn film, E0 versus saturated calomel electrode (SCE), are -0.27, -0.43, -0.55
      V in pH 1 H2SO4 solution and changed linearly with the slope of 44, 63, and 60
      mV/pH in the pH range 0-2, respectively. The BW11Zn/APTMS/GC electrode shows good
      catalytic activity for the reduction of BrO3-, NO2- and H2O2.

PMID- 24734564
TI  - Synthesis and photocatalytic properties of CuO nanostructures.
AB  - CuO nanostructures were grown by decomposition of a mixture of Cu(CH3COO)2 x H2O
      and NaCl at different temperatures. The nanostructure properties were studied by
      X-ray diffractometer, scanning electron microscope and Raman spectroscope.
      Photodegradation activity of the nanostructures towards methyl orange was also
      examined. CuO spheres and hollow spheres composed of nanoparticles were obtained.
      CuO nanoparticle size increases with an increase in the growth temperature. More
      specifically, it increases slowly when the temperature was lower than 280 degrees
      C and increases dramatically in a higher temperature range. The degradation
      activity is sensitive to the nanostructure growth temperatures, but the
      degradation activity varies with the growth temperatures or the size of
      nanoparticles composing of nanospheres non-monotonously. The hollow spheres
      composed of nanoparticles grown at 280 degrees C show superior photocatalytic
      activity towards the degradation of methyl orange than that grown at lower and
      higher temperatures.

PMID- 24734565
TI  - 1D structure of Y2O3:Eu nanorods: controllable synthesis, growth mechanisms and
      luminescence properties.
AB  - Y2O3O:Eu nanorods were successfully synthesized by a facile and effective
      hydrothermal method in the presence of P123 (EO106PO70EO106) as the surfactant
      followed by a subsequent heat treatment process. The scanning electron microscopy
      (SEM) and transmission electron microscopy (TEM) images indicate that the as
      prepared samples consist of nanorods with diameters ranging from 80 nm to 100 nm
      and grow along the (100) direction. The growth mechanism of the as-obtained
      Y2O3:Eu nanorods was proposed on the basis of pH-dependent experiments. It is
      found that the pH is a crucial factor in determining the phase, morphology and
      luminescence properties of Y2O3:Eu nanorods. The luminescent spectra of Y2O3:Eu
      nanorods show the strong characteristic dominant emission of the Eu3+ ions at 613
      nm.

PMID- 24734566
TI  - Photoluminescence of nanosized GdAl3(BO3)4:Sm3+, Eu3+ phosphor under UV
      excitation.
AB  - GdAl3(BO3)4:Eu3+, Sm3+ nanophosphors were successfully prepared by a sol-gel
      process. The nanoparticles have been characterized by X-ray diffraction, scanning
      electron microscopy (SEM) and transmission electron microscopy (TEM) techniques,
      and fluorescence measurements. The results show that the samples are composed of
      nanoparticles 40-60 nm in width. Under 406 nm excitation, the predominant
      emission peak of the GdAl3(BO3)4:Sm3+ nanoparticles is located at 599 nm, which
      is due to the 4G5/2-6H7/2 transition of Sm3+; Eu3+ activated GdAl3(BO3)4 shows
      intense red emission at 613 nm in the emission spectrum under 393 nm excitation,
      belonging to the 5D0-7F2 transition of Eu3+; For the Eu3+/Sm3+ co-doped sample,
      the most intensive emission at 613 nm under 393 nm excitation has been enhanced
      about 54% over that of the Eu3+ single-doped sample, due to an energy transfer
      from Sm3+ to Eu3+.

PMID- 24734567
TI  - The short circuit current improvement in P3HT:PCBM based polymer solar cell by
      introducing PSBTBT as additional electron donor.
AB  - Here we demonstrate the influence of electron-donating polymer addition on the
      performance of poly(3-hexylthiophene) (P3HT):1 -(3-methoxycarbonyl)-propyl-1
      phenyl-(6,6) C61 (PCBM) solar cells. Poly[(4,42-bis(2-ethylhexyl) dithieno [3,2
      b:22,32-d] silole)-2,6-diylalt-(2,1,3-benzothiadiazole)-4,7-diyl] (PSBTBT) was
      chosen as the electron-donating polymer to improve the short circuit current
      (J(sc)) due to its distinct absorption in the near-IR range and similar HOMO
      level with that of P3HT. In the study, we found that J(sc) was improved for
      ternary blend (P3HT:PSBTBT:PCBM) solar cells. The dependence of device
      performance was investigated. J(sc) got decreased with increasing the ratio of
      PSBTBT. Result showed that J(sc) of ternary blend solar cells was improved
      greatly after thermal annealing at 150 degrees C, close to that of the binary
      blend (PSBTBT:PCBM) solar cells.

PMID- 24734568
TI  - Luminescence of AgCl:Ho nanocrystals and applied in IR LEDs used as active
      material.
AB  - AgCl:Ho nanocrystals were synthesized in the aqueous medium from readily
      available precursors. The construction and morphology of AgCl:Ho nanocrystals
      were studied. Vis-NIR absorption, excitation and photoluminescence emission
      spectra of AgCl:Ho nanocrystals were investigated at room temperature. PL spectra
      of AgCl:Ho nanocrystals with different molar ratio of Ho ions excited at 448 nm
      all have broadened emission bands centered around 1000, 1210 and 1540 nm, which
      can be attributed to the 5F5 --> 5I7, 5I6 --> 5I8 and SF5 --> 5I6 energy
      transition, respectively. Moreover, AgCl:Ho nanocrystals used as an active
      material were combined with InGaN diode to fabricate the IR LED which possesses
      the effective near infrared emission.

PMID- 24734569
TI  - Synthesis of gold nanoparticles from different cellular fractions of Fusarium
      oxysporum.
AB  - The addition of varying concentrations of precursor gold salt to different
      cellular fractions of Fusarium oxysporum, viz., the culture filtrate and the
      intracellular extract obtained in the growing and resting phase of the cells had
      a profound influence on the size, shape, and state of aggregation of the
      nanoparticles. Multiply-twinned nanoparticles were obtained when the culture
      filtrate was used for synthesizing nanoparticles while mostly irregular shapes
      were obtained with the intracellular extract. The time taken for the formation of
      gold nanoparticles in the culture filtrate of resting cells was very less (< 30
      min) while it took more than 8 h when the intracellular extract was used for
      synthesis of nanoparticles. There was a reduction in size of the nanoparticles
      with decreasing concentration of the gold salt from 1 mM to 0.05 mM. With the
      intracellular extract, the initial rate of increase in surface plasmon absorption
      maximum was linearly proportional to the initial concentration of the gold salt
      used. Gold nanoparticles were also obtained with the heat-inactivated culture
      filtrate which suggests alternatively the role of peptides and amino acids
      besides proteins in reducing and/or stabilizing the nanoparticles.

PMID- 24734570
TI  - Process optimization of mechano-electrospinning by response surface methodology.
AB  - In this paper, mechano-electrospinning (MES) is presented to write the
      polyvinylidene fluoride (PVDF) solution into fibers directly, and the effects of
      the process parameters on the fiber are investigated experimentally based on
      response surface methodology. The different width of the fiber is obtained by
      adjusting the individual process parameters (velocity of the substrate, applied
      voltage and nozzle-to-substrate distance). Considering the continuous jet and
      stable Taylor-cone, the operation field is selected for investigating the
      complicated relationship between the process parameters on the width of the fiber
      by using the response surface methodology. The experiment results show that the
      predicted width of the fiber is in good agreement with the actual width of the
      fiber. Based on the analysis of the importance of the terms in the equation, a
      simple model can be used to predict the width of the fiber. Depending on this
      model, a large number of calibration experiments can be subducted. Additionally,
      the principle of the selection of the process parameters is presented by
      optimizing parameters, which can give a guideline for obtaining the desired fiber
      in the experiment.

PMID- 24734571
TI  - Structure and characteristics of Li-doped NiO thin films prepared by using pulsed
      laser deposition process.
AB  - 10 at% Li doped NiO thin films were prepared on glass and sapphire single crystal
      substrates by using pulsed-laser deposition (PLD) process. The effects of the
      substrate and the deposition temperature on the crystal structures, electrical,
      and optical properties of NiO thin films were studied by using XRD, 4 point
      probe, and UV-VIS spectrometer. The electrical conductivities and the optical
      properties of NiO thin films depend on the crystallinity of the thin films and
      substrate temperatures. The Li doped NiO thin film with electrical conductivity
      of 2.25 S/cm and optical transmittance of 80% was fabricated on the sapphire
      substrate when processing parameters were optimized.

PMID- 24734572
TI  - Surface plasmon resonance enhanced organic light emitting diode.
AB  - Surface plasmonic structure in solution-processable PHOLED was fabricated by
      blending and spin-coating techniques. ZnO nanoparticles were incorporated into
      the hole injection layer (PEDOT:PSS) by mixing solutions prior the EML spin
      coating. The device structure are ITO/PEDOT:PSS+ ZnO/FIrpic:PVK/BCP/Alq3/LiF/Al.
      Plasmonic structures in PHOLED can be used for the enhancement of performance in
      existing device architectures.

PMID- 24734573
TI  - Delayed electroluminescence of doped fluorescent aingle layer organic light
      emitting devices.
AB  - Doped single-layer polymer OLEDs consisting of PVK: (TPB, C545T, Rubrene or
      DCJTB) were prepared. By applying high-frequency electric pulse of 0.5 micros
      pulse width to each device, we observed various delayed electroluminescence after
      withdrawing the forward bias. The order of magnitude of fitting life time ranges
      from hundreds of nanoseconds to several milliseconds. Current density-voltage and
      brightness-voltage characteristics reveals charge trapped on guest sites
      initially before released. Subsequently, the recombination of these trapped
      charges is strongly involved in the origin of delayed electroluminescence.

PMID- 24734574
TI  - Growth and optical properties of ZnO/MgO core/shell nanoparticles.
AB  - Octylamine capped ZnO/MgO core/shell nanoparticles with different shell thickness
      were grown by thermolysis of metal organic precursors. The as-grown nanoparticles
      and subsequently annealed ones were characterized by X-ray diffractometer,
      transmission electron microscope, high resolution transmission electron
      microscope, and Micro Raman spectroscope. ZnMgO alloys and amorphous MgO formed
      on the surface of the ZnO cores in the as-grown core/shell nanoparticles. MgO
      crystalline formed after annealing at 430 degrees C for 2 h. ZnO cores have
      strong UV emission and weak visible emission. Growth of the shells could enhance
      the intensity of ZnO UV emission by 4.2 times. The thinner shells promote the
      core luminescence more efficiently than thicker ones. After being annealed in air
      at high temperatures, UV luminescence intensities of both pure core and
      core/shell nanoparticles degraded, while the luminescence of the core/shell
      nanoparticles with thinner shells degraded more obviously.

PMID- 24734575
TI  - Improved ultraviolet upconversion emissions of Ho3+ in hexagonal NaYF4
      microcrystals under 980 nm excitation.
AB  - Under 980 nm excitation, enhanced ultraviolet (UV) upconversion (UC) emissions at
      242.4 nm, 276.1 nm, 289.7 nm, 296.4 nm, 303.6 nm, 357.7 nm and 387.8 nm of Ho3+
      ions were observed in beta-NaYF4:20%Yb3+, 1.5%Ho3+ microcrystals (MC) which were
      synthesized through a hydrothermal method. The results indicated that these UV
      emissions came from five- and four-photon UC processes. Dynamical analysis on
      Ho3+ excited states suggests that, for excited Ho3+ ions, the higher the energy
      level is, the shorter the lifetime is.

PMID- 24734576
TI  - Luminescence enhancement in Eu3+, Sm3+ co-doped liy(MoO4)2 nano-phosphors by sol
      gel process.
AB  - A series of LiY(0.95-x)Eu(0.05)Sm(x)(MoO4)2 red light emitting phosphors were
      synthesized by sol-gel technique. The phase impurity and spectroscopic properties
      were characterized by X-ray Diffraction (XRD), Photo-Luminescence (PL) and Photo
      Luminescence Excitation (PLE) spectra, respectively. It is found that the PLE
      spectra of the Eu3+, Sm3+ co-doped nanoparticles are enhanced and broadened as
      compared with the solely doped samples, which will make the co-doped phosphors
      match better with blue and/or UV GaN based LED chips. The red emission intensity
      of Eu3+ is largely enhanced by the energy transfer from Sm3+. The mechanism of
      the enhancement is clearly proven to be the increase in the quantum efficiency of
      5D0 state of Eu3+ rather than the increase in the absorption of Eu3+. Meanwhile,
      the characteristic f-f transitions of Sm3+ are greatly reduced, resulting in
      little influence in the color purity of the co-doped phosphors. The present
      material is an amendatory promising red light emitting phosphor for white LEDs.

PMID- 24734577
TI  - NaYF4 nanocrystals with intense 1530 nm fluorescence for polymer optical
      waveguide amplifiers.
AB  - Alfa-NaYF4:18%Yb,0.2%Er nanocrystals have been synthesized. The average size of
      nanocrystals is 15 nm. The fluorescence spectra of the nanocrystals excited under
      980 nm LD was recorded. An optical waveguide amplifier was fabricated using SU-8
      2005 polymer doped with 0.21 wt% of nanocrytals. For an input signal power of
      0.05 mW and a pump power of 212 mW, a relative optical gain of 3.3 dB at 1520 nm
      was achieved.

PMID- 24734578
TI  - Solvothermal synthesis and upconversion properties of YF3:Ln (Ln =
      Yb/Er,Yb/Tm,Yb/Ho) nanoparticles.
AB  - YF3 nanoparticles with different morphology, dimension, and dispersity have been
      synthesized through a simple solvothermal method by using n-octanol and n
      octylamine as a mixed solvent and lanthanide acetylacetonate as the RE3+ source.
      X-ray diffraction (XRD), scanning electron microscopy (SEM), transmission
      electron microscopy (TEM), high-resolution transmission electron microscopy
      (HRTEM), energy dispersive X-ray spectrum (EDS) and up-conversion (UC)
      photoluminescence spectra were used to characterize the samples. The results
      reveal that the morphology and dimension of the as-prepared nanoparticles can be
      regulated by adjusting n-octanol/ n-octylamine volume ratio in the initial
      system. Besides, by doping with different rare-earth elements (Yb/Er, Yb/Tm,
      Yb/Ho), the as-prepared YF3 samples can emit characteristic green, blue, and
      yellow light under 980 nm laser excitation. Additionally, when being co-doped
      with the activator ion-pairs Tm/Er and Tm/Ho, the color of the emission light can
      be further modified by adjusting the Yb3+ ion content.

PMID- 24734579
TI  - Tuning upconversion luminescence of LiYF4:Yb3+,Er3+/Tm3+/Ho3+ microcrystals
      synthesized through a molten salt process.
AB  - In this paper, well-defined tetragonal-phase LiYF4:Yb3+,Er3+/Tm3+/Ho3+ micro
      crystals with octahedral morphology were successfully prepared through a
      surfactant-free molten salt process for the first time. By gradually increasing
      the LiF content in the NaNO3-KNO3 reaction medium, the crystal phase transforms
      from a mixture of YF3 and LiYF4 to pure tetragonal-phase LiYF4. The possible
      formation process for the phase and morphology evolution is also presented.
      Moreover, upon 980 nm laser diode (LD) excitation, the lanthanide ions (Yb3+,
      Er3+/Tm3+/Ho3+) doped LiYF4 crystals exhibit intense upconversion emission
      lights. By tuning the sensitizer concentrations of Yb3+ ions in LiYF4:Yb3+,Er3+,
      the relative intensities of green and red emissions can be precisely adjusted
      under single wavelength excitation. Consequently, multicolor upconversion
      emissions can be obtained. On the other hand, UC mechanisms were also given based
      on the emission spectra and the plot of luminescence intensity to pump power.

PMID- 24734580
TI  - The regulation of sepiolite surface free energy and its impact on the thermal
      insulation property of coating.
AB  - Surface modification is used to regulate surface free energy of sepiolite with 3
      glycidoxypropyltrimethoxysilanes (3-GPTMS), 3-methacryloxypropyltrimethoxysilanes
      (3-MAPTMS) and 3-mercaptopropyltrimethoxysilane (3-MPTMS). Through
      characterization by Fourier transform infrared spectroscopy, surface free energy,
      zeta potential and sedimentation measurements and infrared emissivity, it is
      found that the surface free energy of 3-MPTMS modified sepiolite decreases to
      31.72 mJ/m2 and the percentage of polar component increases to 89.75%, thus
      leading to that the infrared emissivity of 3-MPTMS modified sepiolite increase to
      be higher than 0.8 and the dispersion of sepiolite has been improved. The
      excellent thermal insulation property of coating is prepared with 10% additive
      amount of 3-MPTMS modified sepiolite and the temperature difference between upper
      and lower box of modified sepiolite coatings is 10 degrees C which is higher than
      the untreated sepiolite.

PMID- 24734581
TI  - Synthesis and optimum luminescence of doughnut-shape undoped and doped CaMoO4.
AB  - In this work, we report the size and shape-controlled synthesis of CaMoO4
      nanocrystals with an aim of investigate their structural, electronic, and
      luminescent properties. The samples were carefully characterized by X-ray
      diffraction, transmission electron microscopy, Fourier transformed infrared
      spectroscopy, UV-vis diffuse reflectance spectroscopy, and luminescence
      spectroscopy. It is found that when MoO4(2-) and Ca2+ were mixed at relatively
      low temperature (in ice salt bath), the reaction produces a uniform population of
      microparticles with an interesting "doughnut" shapes. Due to the low temperature,
      the process of crystal nucleus is slow enough to for separated growth. The
      intensity of the absorption band for CaMoO4 nanocrystals was greatly enhanced
      with the decrease reaction temperature. The as-prepared CaMoO4 doughnut phosphors
      reveal a broad emission with a maximum at 500 nm, which exhibit blue-green
      emission. We also study the luminescent property for Eu(3+)-doped CaMoO4. As for
      the Eu(3+)-doped samples (initial Ca2+:Eu3+ molar ratio 20:1), it is shown that
      Eu3+ was substituted at Ca2+ sites in the CaMoO4 host lattice, which favors
      energy transition between Eu3+ ions and molybdate groups that caused the decrease
      of strength of the peak in emission spectra.

PMID- 24734582
TI  - Electro-catalytic activity of palladium modified nitrogen doped titania
      nanoparticles.
AB  - Pd-modified N-doped TiO2 nanoparticles were prepared by the sol-gel method. The X
      ray diffraction (XRD) pattern indicated that the pure anatase TiO2 has been
      obtained. Transmission electron microscope (TEM) was used to observe the micro
      morphology of the nanoparticles. The average size of the particles was 8.04 nm.
      The N2 adsorption isotherm of the resulted nanoparticles was the type IV with a
      H1 type hysteresis loop. The specific surface area was 145.2 m2 g(-1) and the
      average diameter of adsorption was 4.178 nm. These Pd-modified N-doped TiO2
      nanoparticles were applied onto the surface of glass carbon electrode (GCE), and
      its electro-catalytic activity was tested by cyclic voltammetry (CV). The
      reduction peak currents showed a linear response to the dissolved oxygen (DO)
      concentrations ranging from 0.6 mg L(-1) to 7.2 mg L(-1) on the Pd-N-TiO2/ GCE.
      The linear regression equation was y = 3E - 6x + 1E-5 (R = 0.9909). The detection
      limit was 0.22 mg L(-1.) The result indicated that the Pd-N-TiO2 possessed a good
      electro-catalytic activity.

PMID- 24734583
TI  - Effect of calcination on the visible light photocatalytic activity of N-doped
      TiO2 prepared by the sol-gel method.
AB  - A series of N-doped TiO2 nanoparticle powders have been prepared by the sol-gel
      method using triethylamine as N precursor. The effect of calcination temperatures
      on the quality of the as-prepared samples was studied and an annealing treatment
      was introduced to improve further the quality of the as-prepared sample. The
      visible light photocatalytic activities of the samples were evaluated by
      decomposition of methyl orange (MO) in water. The calcination temperature plays a
      key role in determining the quality of N-doped TiO2 nanoparticle powders. The
      enhancement of calcination temperatures facilitates the crystallization of N
      doped TiO2 powders and the elimination of surface organic residues, but promotes
      the loss of doping N and the agglomeration of nanoparticles and results in low N
      doping level and large particle sizes. The N-doped TiO2 sample (NT-300) calcined
      at 300 degrees C in air for 3 h produced the maximum visible light photocatalytic
      activity. The annealing treatment of NT-300 at its calcination temperature could
      improve the crystallinity, remove effectively the surface organic residues, keep
      nanoparticles in smaller size, and retain the doping N, therefore improving the
      visible light photocatalytic activity significantly.

PMID- 24734584
TI  - Switching mechanism in Au nanodot-embedded Nb2O5 memristors.
AB  - Resistive switching behavior of Au nanodot-embedded Nb2O5 memristor devices is
      reported. Due to controlled formation and/or rupture of conductive filaments; Au
      nanodot-embedded Nb2O5 devices show better consistency during transition from
      high to low resistance state and vice-versa. The memristive transition is
      explained using a physical model which involves oxygen ion, O(2-) trapping or
      detrapping at the metal-oxide interface, and O(2-) transport and annihilation
      with the oxygen vacancies in the breakdown percolation path. The experimental
      results indicate that Au nanodot-embedded Nb2O5 memristors may find applications
      as non-volatile memory devices.

PMID- 24734585
TI  - Gamma-Fe2O3 nanospindles for environmental remediation: a study on the adsorption
      and desorption characteristics of acridine orange and direct red dyes.
AB  - In this paper, the adsorption and desorption characteristics of two harmful dyes,
      i.e., acridine orange (AO; cationic dye) and direct red 81 (DR; anionic dye) from
      aqueous solutions onto gamma-Fe2O3 nanospindles have been investigated. The
      nanospindles were synthesized by facile chemical precipitation method and
      characterized in detail in terms of their morphological, compositional and
      optical properties. Batch mode experiments were conducted to examine the
      adsorption process by investigating several factors such as effect of pH, amount
      of adsorbent dose, and effect of dye concentrations. The experimental results
      indicated that the maximum adsorption capacity occurred at pH = 6.0 for AO and at
      pH = 4.0 for DR, respectively with 0.03 gm of adsorbent. Langmuir, Freundlich,
      Temkin, and Dubinin-Radushkevich isotherm models have been used to evaluate the
      ongoing adsorption. Kinetic parameters for the adsorption have also been applied.
      Moreover, the gamma-Fe2O3 nanospindles and the adsorbed dyes were desorbed with
      good performance and could be reused to absorb the dyes again.

PMID- 24734586
TI  - Effect of mesa structure formation on the electrical properties of zinc oxide
      thin film transistors.
AB  - ZnO based bottom-gate thin film transistor (TFT) with SiO2 as insulating layer
      has been fabricated with two different structures. The effect of formation of
      mesa structure on the electrical characteristics of the TFTs has been studied.
      The formation of mesa structure of ZnO channel region can definitely result in
      better control over channel region and enhance value of channel mobility of ZnO
      TFT. As a result, by fabricating a mesa structured TFT, a better value of
      mobility and on-state current are achieved at low voltages. A typical saturation
      current of 1.85 x 10(-7) A under a gate bias of 50 V is obtained for non mesa
      structure TFT while for mesa structured TFT saturation current of 5 x 10(-5) A
      can be obtained at comparatively very low gate bias of 6.4 V.

PMID- 24734587
TI  - Synthesis and properties of nanohybrid materials with SiO2 and epoxy resin.
AB  - SiO2-epoxy nanohybrid materials were synthesized by hybridization of surface
      modified colloidal silica nanoparticle (CS) and epoxy resin. The CS was surface
      modified with either methyltrimethoxysilane (MTMS) or phenyltrimethoxysilane
      (PTMS) followed by the solvent exchange with dimethylacetamide (DMAc) to have a
      homogenous dispersion in epoxy resin. Various amounts of surface-modified CS were
      mixed with epoxy resin. The chemical structures of surface-modified CS were
      investigated with FT-IR spectroscopy. The particle sizes of CS and surface
      modified CS were measured with DLS. The morphology of hybrid materials analyzed
      using FE-SEM and AFM showed homogeneous dispersion in epoxy resin. The optical
      and thermal properties of the hybrid materials determined by refractive index
      meter and DSC were lower in RI and higher in Tg than neat epoxy resin,
      respectively.

PMID- 24734588
TI  - Performance degradation of c-Si solar cells under UV exposure.
AB  - Current-Voltage (I-V) and Capacitance-Voltage (C-V) characteristics of
      crystalline silicon solar cells were obtained under UV exposure. The solar cell
      parameters degraded with increasing exposure time. For example, open-circuit
      voltage (V(oc)), short-circuit current (J(sc)), fill-factor (FF) and efficiency
      (eta) were degraded. In this study, solar cell did not degrade at the p-n
      junction or silicon substrate effective lifetime by UltraViolet (UV) light
      exposure. The main degradation occurred at the SiN(x) layer, the commonly used
      anti-reflection coating (ARC), due to the positive charges generated by the high
      energy UV light source. UV light changed the characteristics of the SiN(x) layer
      and the Si/SiN(x) interface to degrade the cell efficiency.

PMID- 24734589
TI  - Study on thermal and structural stability of high power light-emitting diode
      lighting system.
AB  - In this paper, we have been analyzed the thermal-fluid flow and structural stress
      of high power Light-emitting diode (LED) lighting system for outdoor lighting.
      Thermal and Structural performances of LED lighting systems were designed using
      computer aided engineering (CAE) and after securing their structural and thermal
      safety, simulated in order to develop 400 W high-efficiency LED floodlight. The
      temperature of LED was shown to rise up to 136 degrees C. This means that the
      cooling system should be improved. Maximum strain was detected in the glass, yet
      they appeared largely safe. It is important for the design to focus on the
      cooling fin. Regarding the lifespan of LED, it is necessary to have a plan for
      minimizing errors when testing designs for optimizing air-cooling structures.
      Which measured the lifetime of the lighting equipment has passed.

PMID- 24734590
TI  - Glucose sensor based on copper oxide nanostructures.
AB  - CuO spheres composed of finely arranged nanobricks were synthesized by simple and
      facile hydrothermal process and used as efficient electron mediators for the
      fabrication of highly sensitive non-enzymatic glucose sensor. The CuO spheres
      were synthesized at low-temperature of -30 degrees C and characterized in terms
      of their morphological, compositional, and structural properties. The
      morphological investigations revealed that the synthesized CuO powder possess
      spherical shapes and made of several CuO nanobricks. The detailed structural
      characterizations exhibited that the synthesized CuO spheres are nanocrystalline
      and possessing monoclinic structure. The fabricated glucose sensor based on CuO
      spheres exhibits a high sensitivity of -164.2523 microA mM(-1) cm(-2) and
      experimental detection limit of -39 microM with a quick response time of -10.0 s.
      The presented work shows that the easily prepared CuO nanomaterials can be used
      as efficient electron mediators for the fabrication of high sensitive non
      enzymatic glucose sensors.

PMID- 24734591
TI  - Humidity sensing by carbon nanocones.
AB  - Carbon nano-structures, mainly nanotubes, have been explored in the past as
      sensing devices. In this report we have considered cones and discs (CNCs)
      subjected to acid treatment, dry oxidation and high temperature annealing, to
      study the modifications induced as they are used as sensing elements of varying
      relative humidity (RH). The relative humidity was varied in cycles of 30 min
      between 36% and 75%. Not strangely, the acid treated films displayed a much
      larger variation in resistance for the same difference in RH (16%). In the as
      grown material, very small variations were detected among cycles under similar
      conditions. The changes induced in the sensors structures by the different
      preparation procedures were characterized by transmission electron microscopy
      (TEM) and Raman reflexion. These results were used to model their behaviour as RH
      sensors.

PMID- 24734592
TI  - Interaction between Rashba and Zeeman effects in a quantum well channel.
AB  - The applied field induced Zeeman effect interferes with Rashba effect in a
      quantum well system. The angle dependence of Shubnikov-de Haas oscillation shows
      that the in-plane term of the applied field changes the intrinsic Rashba induced
      spin splitting. The total effective spin-orbit interaction parameter is
      determined by the vector sum of the Rashba field and the applied field.

PMID- 24734593
TI  - Ultraviolet-enhanced upconversion emission mechanism of Tm3+ in YF3:Yb3+, Tm3+
      nanocrystals.
AB  - Dependences of the spectral profiles on the both Tm(3+)- and Yb3+ additive
      amounts were presented. Further, the temporal evolution of Tm3+ luminescence in
      the nanocrystals was explored. Enhanced ultraviolet emissions with Tm3+
      upconversion were investigated in the Y(0.800-x)Fa:Yb(3+)0.200, Tm3+(x),
      nanocrystal samples following excitation with 980 nm. The emissions can be
      attributed to the transitions of 1G4 --> 3H6, 1D2 --> 3F4 or 3H6 and (3P0 and
      1I6) --> 3F4 or 3H6. A detailed energy-transition scheme was proposed and
      described well the ultraviolet-enhanced upconversion of Tm3+ and the energy
      transfer processes from Yb3+ to Tm3+ based on energy-matching conditions.

PMID- 24734594
TI  - Solution-processable functionalized graphene oxide as an efficient hole transport
      layer in organic photovoltaics.
AB  - Solution-processable functionalized graphene oxide (SPFGO) thin films as the hole
      transport layer in organic photovoltaics (OPVs) are fabricated. The performance
      of the device has been improved by the incorporation of SPFGO. The best results
      of the open-circuit voltage (V(oc)), short-circuit current density (J(sc)), fill
      factor (FF) and power conversion efficiency (PCE) were 0.57 V, 7.7 mA/cm2 0.65,
      and 2.90%, respectively, which are achieved when the thickness of SPFGO film is 3
      nm. The dramatic increase in the PCE of OPVs are comparable to those devices
      fabricated with PEDOT:PSS as the hole transport layers. Therefore, we suggest
      that SPFGO thin films could be a promising solution-processable alternative to
      PEDOT:PSS as the effective hole transport layers (HTLs) in OPV devices.

PMID- 24734595
TI  - 1,8-Diiodooctane as the processing additive to improve the efficiency of
      P3HT:PC61BM solar cells.
AB  - Controlling the blend morphology is critical for achieving high power conversion
      efficiency in polymer/fullerene bulk heterojunction (BHJ) photovoltaic devices.
      As a simple and effective method to control morphology, adding processing
      additives has been widely applied in the organic BHJ solar cells. In this paper,
      we demonstrate that adding 1,8-diiodooctane as a processing additives is an
      effective method to improve the morphology and the efficiency of bulk
      heterojunctions (BHJ) solar cells based on the regioregular poly(3
      hexylthiophene) (P3HT) and a soluble fullerene derivative ([6,6]-phenyl C61
      butyric acid methyl ester, PC61BM). We investigated the unique way in which the
      1,8-diiodooctane plays the rule to enhance the performance of solar cells
      according to different morphology and crystallinity of active layers prepared
      with and without the additive. The morphology is studied with atomic force
      microscopy (AFM) and Grazing Incidence X-ray Diffraction (GIXRD). We also find a
      balance between a large interfacial area for exciton dissociation and continuous
      pathways for carrier transportation when the additive is used.

PMID- 24734596
TI  - Synthesis of water dispersible hexagonal-phase NaYF4:Yb, Er nanoparticles with
      high efficient upconversion fluorescence.
AB  - Yb3+ and EP(3+)-codoped hexagonal-phase NaYF4 nanoparticles are synthesized by a
      simple, safe, and cost-effective method. The results of X-ray powder diffraction
      (XRD) and transmission electron microscopy (TEM) show that the as-synthesized
      nanoparticles are in good accordance with the standard beta-NaYF4 with an average
      diameter of 60 nm after silica coating. The upconversion luminescence of prepared
      material under 980 nm excitation is detected, and the luminescence mechanism is
      discussed.

PMID- 24734597
TI  - Properties of ZnO nanofilms formed at solution interfaces by nanoparticle
      oriention arrangement.
AB  - ZnO nanoparticles with the diameter of 11-33 nm were grown by decomposing a
      mixture of Zn(CH3COO)2 x 2H2O with NaCl and Li2CO3. Compact ZnO nanofilms were
      fabricated with the as-grown nanoparticles at the interfaces of the polar and non
      polar solutions. The nanofilm properties were characterized by X-ray diffraction,
      scanning electron microscope, photoluminescence spectroscope and Raman
      spectroscope. Effects of the nanoparticle size on the nanofilm properties were
      studied. The nanoparticles with smaller sizes would align preferentially along
      [001] orientation during forming a film at an interface of two kinds of
      solutions. The nanofilm photoluminescence and Raman vibration are very sensitive
      to the sizes of the nanoparticles that form the nanofilms. 1LO vibration is
      enhanced in the nanofilms composed of nanoparticles with sizes smaller than 20
      nm. The enhancement is attributed to the high density of deep level defects.

PMID- 24734598
TI  - Effect of heat treatment on the far-infrared emission spectra and fine structures
      of black tourmaline.
AB  - Mineral black tourmaline powders were heat-treated at different temperatures.
      Their crystal structure was studied by X-ray diffractometer. Their infrared
      absorption and emission spectra before and after the heat treatment were analyzed
      by the Fourier transform infrared spectrometer. The corresponding fine structures
      were discussed in detail. The results showed that the powders possessed higher
      infrared emissivity at the band where they showed stronger infrared absorption.
      However, there is no certain correlation between the peak intensity of infrared
      absorption and emissivity values at the same frequency. Because of the crystal
      shrinkage of c-axis, the electronic transitions were stimulated between different
      energy levels, and the abilities of infrared absorption and emission were
      enhanced with increasing the temperature of heat treatment.

PMID- 24734599
TI  - Enhanced luminescence of CaWO4:Eu3+ loaded in SBA-16.
AB  - CaWO4:Eu3+/SBA-16 composites with various molar ratios of Eu3+ to CaWO4(x) were
      successfully synthesized by impregnation and subsequent hydrothermal treatment.
      The physicochemical properties of the resultant composites were well
      characterized by X-ray diffraction (XRD), high-resolution transmission electron
      microscopy (HRTEM), N2 adsorption-desorption, Fourier transform infrared
      spectroscopy (FT-IR) and luminescence spectra. The results demonstrated that the
      resultant CaWO4:Eu3+/SBA-16 composites still had ordered mesostructure, i.e., the
      loading of CaWO4:Eu3+ has little impact on the uniform mesostructure of the host
      matrix SBA-16, but just reduced the specific surface area and pore volume of the
      host matrix. Furthermore, the CaWO4:Eu3+/SBA-16 composites with various x showed
      enhanced luminescent properties than the pure CaWO4:Eu3+ counterparts, and
      reached the highest luminescence intensity when x was 3%.

PMID- 24734600
TI  - Microwave-assisted synthesis and luminescence properties of Cd(1-x)Eu(x)MoO4 red
      phosphor.
AB  - Cd(1-x)Eu(x)MoO4 nanoparticles were prepared by a microwave-assisted method. X
      ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron
      microscopy (TEM) and photoluminescence (PL) spectra were used to characterize the
      structures, morphologies and the luminescent properties of as-prepared products.
      Emission and excitation spectra showed that the phosphor exhibits a dominant red
      emission at 612 nm with excitation wavelength of 330 nm at room temperature. The
      optimized concentration of Eu3+ is 5 mol.% for the highest emission intensity at
      612 nm. The concentration quenching mechanism can be interpreted by the nearest
      neighbor ions interaction of Eu3+ ions. It is found that Eu3+ concentration has
      great impact on the luminescent intensity which is attributed to the variation of
      the local symmetry. The red emission is visible to naked eyes, indicating that
      CdMoO4 may act as a promising host material for Eu3+ doped red phosphors.

PMID- 24734601
TI  - The role of Fe3O4 nanocrystal film in bilayer-heterojunction CuPc/C60 solar
      cells.
AB  - The CuPc/C60 thin-film bilayer-heterojunction solar cells are fabricated by
      vacuum deposition with bathocuproine (BCP) as the exciton-blocking layer.
      Ferroferric oxide (Fe3O4) nanocrystal film is inserted between the copper
      phthalocaynine (CuPc) layer and indium tin oxide (ITO) anode. The device
      performances dependent on the thickness of Fe3O4 are investigated and compared.
      The results show that both the short-circuit current density and fill factor are
      enhanced by introducing a 1 nm Fe3O4 buffer layer, leading to an increase of
      power conversion efficiency. The role of Fe3O4 as a buffer layer in the
      improvement of the device performances is studied in detail by ultraviolet
      photoemission spectroscopy (UPS).

PMID- 24734602
TI  - Intense near-infrared quantum cutting emissions in LaF3:Sm3+ nanocrystals.
AB  - In this letter, visible to near-infrared (NIR) quantum cutting (QC) luminescence
      of -20 nm LaF3:Sm3+ (0.2-1 mol%) nanocrystals (NCs) was first studied. A number
      of novel NIR QC emissions (850-2000 nm) were distinguished. The results show that
      the QC emission lines and populating channels depend strongly on Sm3+
      concentration due to the cross relaxation processes. The overall QC efficiency is
      as high as -193% in LaF3:Sm3+ (0.4 mol%) NCs, which shows that NIR QC of Sm3+ is
      of great significance for enhancing the efficiency of solar cells.

PMID- 24734603
TI  - Luminescent properties of LuVO4:Eu3+,Bi3+ red phosphor for light-emitting diodes.
AB  - White light-emitting diodes have recently attracted great attention as promising
      candidates for next-generation lighting. The LuVO4:Eu3+,Bi3+ as new near
      ultraviolet excited phosphors were synthesized via high-temperature solid-state
      reactions. The X-ray diffraction, excitation spectra, emission spectra and decay
      lifetimes of the phosphors were measured to characterize the structure and
      luminescent properties. With Bi3+ doping, the edge of excitation band
      corresponding to the Eu3+ emission shifts from 350 nm to 400 nm with the help of
      Bi(3+)-V5+ metal-metal charge transfer. Consequently, the phosphor exhibits
      efficient absorption of near-ultraviolet excitation, and it also exhibits
      excellent performance in emission intensity compared with the Y2O2S:Eu3+ phosphor
      in current use. This red-emitting material may be applied as a promising red
      phosphor for near-ultraviolet excited white light-emitting diodes.

PMID- 24734604
TI  - Differences in photoluminescence properties and thermal degradation between
      nanoparticle and bulk particle BaMgAl10O17:Eu2+ phosphors under UV?VUV
      irradiation.
AB  - BaMgAl10O17:Eu2+ (BAM) phosphors used for plasma display panels and three-band
      fluorescence lamps are exposed to an oxidizing environment at about 500 degrees
      C, which is currently unavoidable in actual applications. We investigated the
      mechanism of the luminance degradation of BAM caused by annealing at 500 degrees
      C based on the difference in luminance degradation of bulk particle and
      nanoparticle samples under various excitation source irradiations. When the
      samples were excited by the different light sources, more than 30% degradation of
      luminance occurred under 147 nm while less than 10% degradation occurred under
      254 nm both for nanoparticle and bulk particle samples. In addition, the
      luminescence degradation of nanophosphors shows a different tendency compared to
      the bulk phosphors. With a model based on the particle size and excitation light
      penetration depth, we demonstrate that the degradation is still mainly ascribed
      to the oxidized of divalent Eu. The differences in luminescence properties
      between nanophosphors and bulk phosphors are also illustrated by this model. As a
      result, the potential industrial applications of nanophosphors are evaluated.

PMID- 24734605
TI  - Transition from Eu3+ to Eu2+ in SiO2 matrix prepared by sol-gel.
AB  - Activated silica matrix fluorescent materials doped with Al3+ and Eu2+ are
      prepared by sol-gel method. The effects of different atmospheres and annealing
      temperatures on luminescent properties are characterized by analysis techniques
      including X-ray diffraction, infrared spectroscopy and fluorescence spectra. When
      being excited at 281 nm wavelength, the fluorescent materials show a strong broad
      blue emission band, with the emission center at 430 nm and the FWHM of 56 nm. The
      results indicate that the blue emission is derived from 4f6 5d to 4f7 transition
      of the Eu2+ ions. Al3+ ion plays a key role in the process of deoxidization from
      Eu3+ to Eu2+. Al3+ and B3+ can enhance the blue-emission intensity. Also it is
      found that the highest luminescent intensity of the samples occurs in the sample
      Eu-03 annealed at 1150 degrees C in N2 atmosphere.

PMID- 24734606
TI  - Luminescence properties of Y2O3:Eu3+ nanocrystals prepared by the ultrasonic
      chemistry method.
AB  - Y2O3:Eu3+ nanocrystals were prepared by ultrasonic chemistry and characterized by
      scanning electron microscopy (SEM) and X-ray diffraction (XRD). The resulting
      nanocrystals were found to be nanoparticles with size distribution in the range
      of 50-80 nm. The phase of all the samples was cubic. The luminescence properties
      of the samples were systematically studied and show significant change with
      concentration of surfactant and annealing temperature. The results show that the
      intensity of the excitation and emission spectra of Y2O3:Eu3+ nanocrytals
      increases gradually with increasing P123 concentration and annealing temperature.
      The fluorescence lifetime of 5D0 level Eu3+ decreases with increasing P123
      concentration and increases with annealing temperature. The photoluminescence
      stability of Y2O3:Eu3+ nanocrytals becomes worse with increasing P123
      concentration and annealing temperature.

PMID- 24734607
TI  - Preparation and ethanol sensing properties of In2O3 nanotubes.
AB  - In this paper, In2O3 nanotubes were prepared by an electrospinning method
      combined with an oriented-contract calcinations scheme, and characterized by
      differential thermal and thermal gravimetric analyzer (DTA-TGA), X-ray
      diffraction (XRD), and scanning electron microscopy (SEM). Ethanol sensing
      properties of the as-prepared nanotubes were investigated. The results showed
      that the In2O3 nanotubes were obtained at a fast heating rate of 100 degrees
      C/min. Ethanol sensing properties indicated that the nanotubes exhibit a high
      response of 87.5 to 500 ppm ethanol, fast response (20 s) and recovery (18 s)
      rate at the optimal operating temperature of 260 degrees C. Moreover, the
      nanotubes also exhibit good selectivity.

PMID- 24734608
TI  - Electrical coating method of graphene oxide.
AB  - In this work, we use the electrical method to coat graphene oxide (GO) on ITO
      (Indium Tin Oxide) glass. The coated GO was characterized by Raman spectroscopy
      and X-ray photoelectron spectroscopy (XPS). The coated surface was monitored by
      scanning electron microscope (SEM) and atomic force microscope (AFM). Based on
      this coating method, we can control the thickness of GO film by changing the
      applied voltage. Result of thickness control was analyzed by AFM and
      transmittance measurement. Also this method can selectively deposition of GO film
      is possible on patterned ITO. This result was confirmed by Raman spectroscopic
      mapping.

PMID- 24734609
TI  - Optical and structural properties of Al-ZnO nanocomposites.
AB  - The optical and structural properties of aluminium-doped zinc oxide (AZO) films
      were investigated by photoluminescence (PL) spectroscopy, X-ray diffraction
      (XRD), and scanning electron microscopy. Pure zinc oxide (ZnO) and AZO composite
      films were deposited using vacuum evaporation method. The films exhibited
      different morphologies and crystallinity depending on the Al-doping. The SEM
      micrographs showed that a granular and compact structure could be seen for the
      ZnO film, while a nanoleaf structure with relatively porous nature was observed
      for the AZO composite film. The XRD patterns indicated that the crystalline
      growth orientation would be significantly affected by addition of Al. Compared
      with pure ZnO, the XRD peak intensity of the AZO composite was stronger and the
      line-width was narrower. Two-probe resistivity measurements showed that the AZO
      composites could be used as transparent conducting materials. The PL spectra
      revealed that the PL intensities of the AZO composites were stronger than that of
      the pure ZnO. The PL enhancement might be ascribed to the surface plasmon
      resonance of metal nanoclusters within the composite. Another possible reason of
      the PL enhancement would be the metal-induced crystallization caused by doping Al
      to ZnO matrix.

PMID- 24734610
TI  - Effect of Fe doping on optical and magnetic properties of ZnO nanorods.
AB  - Fe-doped ZnO nanorods were synthesized by solvothermal method with Fe
      concentration of 2%, 5% and 10%, respectively. The morphological and structural
      properties of the Fe-doped ZnO nanorods were investigated using scanning electron
      microscopy (SEM), transmission electron microscopy (TEM) and X-ray diffraction
      (XRD) technique, respectively. The presence of Fe doping with different
      concentration was confirmed by X-ray fluorescence (XRF) spectroscopy. For largest
      doping concentration of Fe, the optical band gap of ZnO was found to shift
      considerably about 25% to lower energies than that of the pristine ZnO.
      Furthermore the magnetic behavior was investigated on doped and undoped ZnO
      samples at room temperature as well as at low temperature. We found that these
      nanorods do not exhibit room temperature ferromagnetism. Instead a
      superparamagnetic-type behavior is observed for all the concentration with the
      blocking temperature in the range 13-35 K.

PMID- 24734611
TI  - 3-D perpendicular assembly of single walled carbon nanotubes for complimentary
      metal oxide semiconductor interconnects.
AB  - Due to their superior electrical properties such as high current density and
      ballistic transport, carbon nanotubes (CNT) are considered as a potential
      candidate for future Very Large Scale Integration (VLSI) interconnects. However,
      direct incorporation of CNTs into Complimentary Metal Oxide Semiconductor (CMOS)
      architecture by conventional chemical vapor deposition (CVD) growth method is
      problematic since it requires high temperatures that might damage insulators and
      doped semiconductors in the underlying CMOS circuits. In this paper, we present a
      directed assembly method to assemble aligned CNTs into pre-patterned vias and
      perpendicular to the substrate. A dynamic electric field with a static offset is
      applied to provide the force needed for directing the SWNT assembly. It is also
      shown that by adjusting assembly parameters the density of the assembled CNTs can
      be significantly enhanced. This highly scalable directed assembly method is
      conducted at room temperature and pressure and is accomplished in a few minutes.
      I-V characterization of the assembled CNTs was conducted using a Zyvex
      nanomanipulator in a scanning electron microscope (SEM) and the measured value of
      the resistance is found to be 270 komega s.

PMID- 24734612
TI  - Sensitized luminescence of LaF3:Eu3+ nanoparticles through pyromellitic acid.
AB  - The LaF3 nanoparticles doped with different concentration Eu3+ ions are prepared
      by a simple and low temperature synthetic route. The nanoparticles with the size
      of about 3.5 nm are roughly spherical and monodisperse. The emission of Eu3+ ions
      is sensitized through pyromellitic acid bonded onto the surface of nanoparticles.
      The structure, morphology, photoluminescence properties and fluorescence dynamics
      are studied systemically. The results show that the sensitized nanoparticles have
      a broad absorption band in the UV domain and high asymmetry radio, and enhanced
      Eu3+ luminescence by "antenna effect" of ligands. The excited state lifetimes of
      sensitized nanoparticles are longer than those of un-sensitized nanoparticles and
      corresponding europium complexes.

PMID- 24734613
TI  - Luminescence properties of Tb3+, Eu3+, Tm3+ co-doped Na5La(MoO4)4 for white light
      emitting diode.
AB  - Tb3+, Eu3+, Tm3+ co-doped Na5La(MoO4)4 phosphors were prepared by the
      conventional solid-state reaction. Under the excitation of UV light,
      Na5La(MoO4)4:Tm3+, Na5La(MoO4)4:Tb3+, and Na5La(MoO4)4:Eu3+ exhibit the
      characteristic emissions of Tm3+ (1D2 --> 3F4, blue), Tb3+ (5D4 --> 7F5, green),
      and Eu3+ (5D0 --> 7F2, red), respectively. By adjusting the doping concentration
      of rare earth ions in Na5La(MoO4)4:a Tm3+, b Tb3+, c Eu3+, a white emission in a
      single composition was obtained under the excitation of 362 nm. It might be a
      promising phosphor for the future applications.

PMID- 24734614
TI  - Enhanced near-infrared upconversion luminescence of GdF3:Yb3+, Tm3+ by Li+.
AB  - GdF3:0.23Yb3+, 0.005Tm3+, x%Li+ (x = 0-7) NIR to NIR upconversion nanocrystals
      (UCNPs) were synthesized by a hydrothermal method. Their XRD patterns show that
      they are all orthorhombic phase despite of different Li+ ion concentrations. The
      detailed analysis indicates that lithium ions substitute Gd3+ sites at x < 3. As
      the Li+ content increases, more Li+ ions enter host lattice interstitially. The
      doped Li+ ions affect the crystal field symmetry around Tm3+ ions, which results
      in the change of the irradiation transition probabilities between their
      corresponding transition levels. Compared with GdF3:0.23Yb3+, 0.005Tm3+, the NIR
      to NIR upconversion emission intensity of GdF3:0.23Yb3+, 0.005Tm3+, 0.03Li+
      nanocrystals (excitation at 980 nm, emission at 808 nm) increases 2.2 times.

PMID- 24734615
TI  - Bioconjugations of polyethylenimine-capped LaF3:Ce, Tb nanoparticles with bovine
      serum albumin and photoluminescent properties.
AB  - Water-soluble Ce3+ and Tb3+ co-doped LaF3 nanoparticles with surfaces
      functionalized by a layer of polyethylenimine (PEI) were synthesized via a facile
      one-step hydrothermal method. Bovine serum albumin (BSA) protein was conjugated
      with LaF3:Ce, Tb nanoparticles via free amino groups on the surfaces of the
      nanocrystals. The final products were characterized by X-ray diffraction (XRD),
      field emission scanning electron microscopy (FE-SEM), ultraviolet (UV)
      spectrophotometry, and photoluminescence (PL) spectroscopy. XRD results showed
      that pure hexagonal phase LaF3:Ce, Tb nanoparticles could be obtained via a PEI
      assisted hydrothermal process at 180 degrees C for 24 h. The FE-SEM results
      showed that the morphology of pure LaF3:Ce, Tb nanoparticles was spherical with
      an average diameter of -20 nm. The UV spectra showed that BSA had been conjugated
      with LaF3:Ce, Tb nanoparticles. The photoluminescent (PL) properties of LaF3:Ce,
      Tb nanoparticles were also studied. The strong green emission of Tb3+ in LaF3:Ce,
      Tb nanoparticles suggests that these nanoparticles may have potential
      applications for labels in biological imaging and immunoassays.

PMID- 24734616
TI  - Polymer-mediated tunneling transport between carbon nanotubes in nanocomposites.
AB  - Electron transport in nanocomposites has attracted a good deal of attention for
      some time now; furthermore, the ability to control its characteristics is a
      necessary step in the design of multifunctional materials. When conductive
      nanostructures (for example carbon nanotubes) are inserted in a non-conductive
      matrix, electron transport below the percolation threshold is dominated by
      tunneling and thus the conductive characteristics of the composite depends
      heavily on the characteristics of the tunneling currents between nanoinserts. A
      parameter-free approach to study tunneling transport between carbon nanotubes
      across a polymer matrix is presented. The calculation is done with a combination
      of Density Functional Theory and Green functions (an approach heavily used in
      molecular electronics) which is shown here to be effective in this non-resonant
      transport condition. The results show that the method can effectively capture the
      effect of a dielectric layer in tunneling transport. The current is found to
      exponentially decrease with the size of the gap for both vacuum and polymer, and
      that the polymer layer lowers the tunneling barrier enhancing tunneling
      conduction. For a polyacrylonitrile matrix, a four-fold decrease in the tunneling
      constant, compared to tunneling in vacuum, is observed, a result that is
      consistent with available information. The method is very versatile as any DFT
      functional (or any other quantum mechanics method) can be used and thus the most
      accurate method for each particular system can be chosen. Furthermore as more
      methods become available, the calculations can be revised and improved. This
      approach can be used to design functional materials for fine-tunning the
      tunneling transport, for instance, the effect of modifying the nanoinsert-matrix
      interface (for example, by adding functional groups to carbon nanotubes) can be
      captured and the comparative performance of each interface predicted by
      simulation.

PMID- 24734617
TI  - Functionalized bio-artifact fabricated via selective slurry extrusion. Part 2:
      Fabrication of ceramic dental crown.
AB  - Functionalized ceramic dental crown was successfully fabricated through selective
      slurry extrusion (SSE) based technique of solid freeform fabrication (also known
      as rapid prototyping). After sintering, the decomposed tourmaline powders were
      embedded in ZrO2 matrix. The far infrared emission properties of the ceramic
      dental crown were improved due to the increase of the numbers of infrared active
      bonds from tourmaline. This new dental restoration process presents potential to
      provide dental patients with functionalized artificial teeth, which benefits the
      body health by the way of emitting far infrared rays in ambient temperatures.

PMID- 24734618
TI  - Controlled synthesis and tunable upconversion luminescence of NaYW2O8:Yb3+/Ho3+
      nanocrystals.
AB  - Tetragonal phase NaYW2O8:Yb3+/Ho3+ nanocrystals were successfully synthesized
      using a hydrothermal method with a subsequent calcination treatment. Under 980 nm
      excitation, the 5S2/5F4 --> 5I8 and 5F5 --> 5I8 emissions were observed. The
      relative intensity of the 5F5 --> 5I8 to the 5S2/5F4 -->5I8 in the samples
      increased with increasing the pH values of the resultant solutions. The CIE
      coordinates of the upconversion luminescence were (0.43, 0.54), (0.41, 0.55),
      (0.40, 0.56), (0.39, 0.54), (0.37, 0.49), (0.35, 0.44), and (0.33, 0.37) for the
      samples prepared at pH = 7, 8, 9, 10, 11, 13, and 14, respectively. In addition,
      the upconversion mechanism was also investigated.

PMID- 24734619
TI  - Synthesis, phase structure and up-conversion luminescence of NaYF4:Yb3+,
      Er3+/Tm3+ nanorods.
AB  - Upconversion luminescent NaYF4:Yb3+, Er3+/Tm3+ nanocrystals were successfully
      synthesized via a facile and one-pot solvothermal method using oleic
      acid/oleylamine (OA/OM) as surfactants. The effects of synthetic parameters
      including rare earth ion doping concentrations and temperatures on the crystal
      phase structure, size and shape of NaYF4:Yb3+, Er3+/Tm3+ nanocrystals were
      systematically investigated. By modulating the synthetic parameters, the shape of
      NaYF4:Yb3+, Er3+/Tm3+ nanocrystals were controlled in forms of nanorods and
      nanowires. The reaction temperature has large effects on the phase structure of
      NaYF4:Yb3+, Er+/Tm3+ nanorods, exhibiting a phase transformation from cubic phase
      (alpha-) in low temperatures to hexagonal phase (beta-) in high temperatures.
      Moreover, the upconversion luminescence of NaYF4:Yb3+, Er3+/Tm3+ nanocrystals was
      found to be dependent on the rare earth ion doping concentrations and
      temperatures.

PMID- 24734620
TI  - Oleic acid-modified LiYF4:Er,Yb nanocrystals for potential optical-amplification
      applications.
AB  - LiYF4:18%Yb, 2%Er nanocrystals and NaYF4:18%Yb,2% Er nanoparticles (NCs) were
      synthesized by a solvothermal approach using oleic acid (OA) as the surfactant.
      With the excitation of a 980 nm diode laser, LiYF4:18%Yb, 2%Er NCs exhibit more
      strong emission than alpha-NaYF4:18%Yb, 2%Er at around 1530 nm. The TEM images
      showed that the LiYF4:18%Yb, 2%Er NCs have a nearly spherical shape and the size
      is about 15 nm. The OA-capped LiYF4 NCs have excellent dispersibility in organic
      solvents. These results showed that LiYF4:18%Yb, 2%Er NCs are a promising
      material for polymer-based optical waveguide amplifiers.

PMID- 24734621
TI  - Ultraviolet upconversion emissions of Gd3+ in beta-NaLuF4:Yb3+,Tm3+,Gd3+
      nanocrystals.
AB  - Beta-NaLuF4:20%Yb,0.5%Tm,x%Gd (x = 10, 20, 30) nanocrystals were synthesized by
      high temperature thermal decomposition method. X-ray diffraction (XRD) show the
      as-prepared samples are characteristic of a pure beta-NaLuF4. Transmission
      electron microscope (TEM) investigations indicate the nanocrystals have particle
      size of -85 nm with good monodispersity and well-defined crystallographic facets.
      Particularly, under 980 nm excitation, upconversion (UC) emissions in the UV
      range of 270-320 nm were observed in these nanocrystals, which further prove that
      beta-NaLuF4 is an excellent host for building UV compact solid-state lasers or
      fiber lasers.

PMID- 24734622
TI  - Preparation and upconversion luminescence of beta-NaYF4:Yb3+, Tm3+/ZnO
      nanoparticles.
AB  - Beta-NaYF4:Yb3+, Tm3+/ZnO core/shell nanoparticles (NPs) were synthesized via a
      high temperature thermal decomposition method. The as-synthesized core/shell NPs
      were characterized by X-ray diffraction (XRD), transmission electron microscopy
      (TEM), and upconversion luminescence spectra (UCL). Under 980 nm laser
      excitation, the measured intensity of upconversion luminescence (1I6 --> 3H6, 1I6
      --> 3F4, and 1D2 --> 3H6) was different with and without ZnO. During the sample
      preparations, changing the ratio of the solvent affected the ZnO UV absorption
      efficiency. The results show that the NIR light can be used as the driving source
      to excite ZnO, thus extending utility rate to the NIR spectral region and
      enhancing the light harvest rate.

PMID- 24734623
TI  - Photovoltaic properties of Zr(x)Ti(1-x)O2 solid solution nanowire arrays.
AB  - In this paper, Zr(0.05Ti(0.95)O2 solid solution nanowire arrays (NWs) were
      prepared by a low temperature hydrothermal method. The as-prepared NWs were
      characterized by scanning electron microscopy (SEM), X-ray diffraction (XRD), X
      ray photoelectron spectroscopy (XPS), and UV-visible (UV-vis) spectroscopy. With
      the doping of Zr content, the band gap of the composite can be varied in a wide
      range and excellent photoelectric properties of the arrays could be obtained.
      Moreover, a preliminary study on the photoelectric properties was conducted,
      which indicates potential applications of the arrays for fabricating high
      performance ultraviolet photodetectors.

PMID- 24734624
TI  - Luminescent properties of NaGdF4: Ln3+ (Ln3+ = Ce3+, Tb3+) phosphors.
AB  - Ln3+ (Ln3+ = Ce3+, Tb3+) single doped and/or co-doped NaGdF4 phosphors have been
      synthesized through a solid state reaction method under a weak reducing N2/H2
      (95/5) atmosphere. The phosphors were characterized by X-ray diffraction (XRD)
      patterns, room temperature photoluminescence (PL) excitation and emission
      spectra, and luminescent dynamics decay curves. XRD analysis indicated that the
      phosphors were in the hexagonal phase and crystallized well. Under Ce3+ 4f-5d 252
      nm excitation, the Ce3+ single doped phosphor emitted near ultraviolet light
      peaking at 398 nm. Under host Gd3+ 275 nm sensitization and direct Tb3+ 4f-4f 380
      nm excitation, the Tb3+ single doped NaGdF4 phosphor gave blue and/or green
      light. Under sensitizer Ce3+ 4f-5d 252 nm and host Gd3+ 4f-4f 275 nm
      sensitization and direct Tb3+ 4f-4f 380 nm excitation, the Ce3+/Tb3+ co-doped
      NaGdF4 phosphors had blue and/or green light. With fixed Ce3+ concentrations in
      the Ce3+/Tb3+ co-doped phosphors, the blue light of Tb3+ became weaker and the
      green light of Tb3+ became stronger with the increase of Tb3+ concentrations,
      which was caused by the cross relaxation process 5D3 --> 5D4:7F6 --> F0. The
      experimental results suggested that the Ce3+/Tb3+ co-doped and Tb3+ single doped
      NaGdF4 phosphors might be used as blue and/or green light emitting materials.

PMID- 24734625
TI  - Pr(3+)-doped beta-NaYF4 for temperature sensing with fluorescence intensity ratio
      technique.
AB  - Pure beta-NaYF4:0.8%Pr3+ powder sample was synthesized by the hydrothermal
      method. The temperature dependence of the fluorescence intensity ratio (FIR) of
      emission bands corresponding to the 3P1 --> 3H5 and 3P0 --> 3H5 transitions was
      measured in the temperature range of 120 K to 300 K excited by a 473 nm
      continuous wave (CW) laser. The dependence of the FIR on temperature is well
      fitted with an exponential function and the effective energy difference obtained
      is 457 cm(-1), which gives further an absolute temperature sensitivity of 0.01352
      K(-1) at 300 K. The monotonous increase of FIR with temperature and high absolute
      temperature sensitivity demonstrate that this material can be used as temperature
      sensor. In addition, mono-dispersed NaYF4:1%Pr3+ nanoparticles were also
      synthesized.

PMID- 24734626
TI  - The luminous and magnetic properties of Tb3+-doped four angle star-like
      NaGd(WO4)2.
AB  - Four angle star-like double tungstates NaGd(WO4)2 have been prepared
      hydrothermally with cetyl trimethyl ammonium bromide (CTAB) as the chelating
      agent and ethanol as the mixing solvent. Monodisperse micron-sized four angle
      star-like NaGd(WO4)2 were fabricated for the first time. The samples were
      characterized by powder X-ray diffraction (XRD), scanning electron microscopy
      (SEM), Fourier transform infrared spectroscopy (FT-IR), and vibrating sample
      magnetrometer (VSM) techniques. This work emphasizes the luminescence properties
      of Tb(3+)-doped NaGd(WO4)2 under ultraviolet (UV) and vacuum ultraviolet (VUV)
      excitation and the magnetic properties. The results demonstrate the phosphors are
      expected to have potential applications in weak lighting systems and magnetic
      resonance imaging.

PMID- 24734627
TI  - Significant enhancement of yellow-green light emission of TiO2 thin films using
      Au localized surface plasmons: effect of dielectric MgO spacer layer thickness.
AB  - TiO2/MgO/Au composite thin films with different MgO spacer layer thicknesses (0
      41 nm) were fabricated on c-sapphire substrates by sputtering and pulsed laser
      deposition. Through optimizing the thickness of MgO spacer layer, which can
      effectively prevent nonradiative Forster resonant energy transfer and charge
      transfer between Au and TiO2, defect-related yellow-green light emission of TiO2
      thin film was greatly enhanced - 12 times. The enhancement mechanism is
      attributed to the efficient increase of luminescence efficiency of deep levels in
      TiO2 induced by resonant coupling between localized surface plasmons in Au
      nanoparticles and electron-hole pairs in defect-related levels of TiO2.

PMID- 24734628
TI  - Synthesis of gold microstructures with surface nanoroughness using a deep
      eutectic solvent for catalytic and diagnostic applications.
AB  - We synthesized highly monodisperse gold microparticles (AuMPs) using a deep
      eutectic solvent (DES) which composed of choline chloride and malonic acid as
      both a reaction medium and structure-directing agent. These microparticles
      exhibit distinctive surface nanoroughness and highly defined diameters that can
      be precisely controlled over a range of a few micrometers under different
      reductive conditions. The internal and external structures of the particles are
      thoroughly investigated by electron microscopy, which is further analyzed in
      association with their optical properties. We also investigate the gold
      microparticle concentration-dependent catalytic property employing a reductive
      reaction of 4-nitrophenol to 4-aminopenol as a model system. Importantly, the
      gold microparticles are densely functionalized with DNA and reversibly assemble
      with DNA-gold nanoparticle conjugate probes for the colorimetric detection of
      target DNA sequences, demonstrating that these novel structures can be utilized
      as platforms that quickly regulate the optical properties of plasmonic
      nanoparticles for diagnostic applications.

PMID- 24734629
TI  - Tungsten disulfide-multiwalled carbon nanotube hybrid anode for lithium-ion
      battery.
AB  - The present work is focused on the preparation of tungsten disulfide-multiwalled
      carbon nanotube (WS2-MWCNT) hybrids by simple dry grinding of WS2 and MWCNT in
      different proportion by weight (1:3, 1:1, 3:1). The as prepared hybrids have been
      characterized by X-ray diffraction (XRD), field emission scanning electron
      microscopy (FESEM), high resolution transmission electron microscopy (HRTEM) and
      Raman analyses. XRD results indicated complete exfoliation of MWCNT among WS2
      particles in WS2-MWCNT (3:1) and (1:1) hybrids. FESEM images showed the formation
      of a 3-D network in WS2-MWCNT (1:1) hybrid with uniform dispersion of MWCNT being
      evident from HRTEM images. Raman analysis also suggested significant interaction
      between WS2 and MWCNT. WS2-MWCNT (1:1) hybrid, when used as anode material in
      lithium ion battery, exhibited a high initial charge capacity (483 mA h g(-1))
      and an improved cycling stability with over 80% retention of the first cycle
      capacity after 20 cycles compared to only 40% capacity retention in pristine WS2.
      Such enhanced electrochemical performance of WS2-MWCNT (1:1) hybrid has been
      attributed to synergistic effect of WS2 and MWCNT.

PMID- 24734630
TI  - Synthesis and characterizations of ferrite nanomaterials for phenyl hydrazine
      chemical sensor applications.
AB  - This paper presents the synthesis, characterization and phenyl hydrazine chemical
      sensing applications of Cd0.5Mg0.5Fe2O4 ferrite nanoparticles. The nanoparticles
      were synthesized by facile and simple co-precipitation method and characterized
      in detail in terms of their morphological, structural, compositional and
      electrical properties. The detailed characterization studies revealed that the
      prepared nanoparticles are grown in high density, possessing Cd0.5Mg0.5Fe2O4
      composition and exhibiting spinel cubic structure. Moreover, the prepared
      Cd0.5Mg0.5Fe2O4 ferrite nanoparticles were used as efficient electron mediators
      for the fabrication of high-sensitive, robust, reliable and reproducible phenyl
      hydrazine chemical sensor by simple I-V technique. The fabricated chemical sensor
      exhibits a highsensitivity of 7.01 microA mM(-1) cm(-2) with an experimental
      detection limit of 3.125 mM in a short response time of -10.0 s. This work
      demonstrates that Cd0.5Mg0.5Fe2O4 ferrite nanoparticles can efficiently be
      utilized for the fabrication of highly sensitive and reliable chemical sensors.

PMID- 24734631
TI  - Dip-coating of nano-sized CeO2 on SiC membrane and its effect on thermal
      diffusivity.
AB  - CeO2-SiC mixed composite membrane was fabricated with porous SiC ceramic and
      cerium oxide powder synthesized by sol-gel process. This CeO2-SiC membrane and
      SiC membrane which is made by the purified SiC ceramic were pressed and sintered
      in Ar atmosphere. And then, the SiC membrane was dip-coated by cerium oxide
      precursor sol solution and heat-treated in air. The surface morphology, particle
      size, porosity and structure analysis of the mixing and dip-coating SiC membrane
      were monitored by FE-SEM and X-ray diffraction analysis. Surface area, pore
      volume and pore diameter were determined by BET instrument. Thermal diffusivity
      was measured by laser flash method with increasing temperature. The relation
      between porosity and thermal diffusivity from different preparation process has
      been discussed on this study.

PMID- 24734632
TI  - Formation and characterization of wrinkle structures of chemically-derived
      graphene thin films and micropatterns.
AB  - In this study, we report a simple and effective process for the fabrication of
      wrinkle structures of chemically derived graphene thin films and patterns.
      Reduced graphene oxide (rGO) thin films/patterns formed on glass substrates are
      transferred to pre-strained elastomeric layers by improving adhesion strength at
      the rGO/PDMS interface with the assistance of oxygen plasma treatment. The
      morphology of rGO wrinkle structures is investigated in the various applied
      strains and film thicknesses. The experimental results were interpreted by
      theoretical models and well fitted to the estimated values. The techniques for
      such well-defined rGO wrinkle structures could be used for flexible and
      stretchable graphene-based electronic devices.

PMID- 24734633
TI  - Electric field effect on the magnetic property of Mn adatom on graphene: Ab
      initio calculations.
AB  - Changes in the magnetic property of the Mn transition metal on graphene were
      observed using density functional calculations (DFT) where the Mn/graphene system
      was enforced by an external electric field. The magnetic moment of the Mn adatom
      on graphene showed continuous changes as a result of the external field. Analysis
      of the charge redistribution of the system revealed that the electrons are
      partially transferred between graphene and the Mn adatom from the effect of the
      external electric field. According to the density of states (DOS) data, the
      transferred charge originates from the electrons in 3d spin down states. In this
      study, it was found that the external electric field affected the changes in the
      electronic structure of the outermost shell of the Mn adatom, and this change
      resulted in change in the magnetic moment.

PMID- 24734634
TI  - Influence of citric acid molar ratio on the sintering behavior of nanocrystalline
      BaCe0.8Sm0.2O(3-delta).
AB  - The samarium-doped barium cerate (BaCe0.8Sm0.2O(3-delta), BCS) nano crystalline
      powders were synthesized via citric-nitrate method. The BCS nanopowders were
      prepared with various molar ratio of citric acid to metal nitrate. The pure
      perovskite structure was obtained from the BCS calcinated at 1200 degrees C and
      its crystalline size was increased with increase of the molar ratio citric acid
      to metal nitrate, while the aggregated particle size was significantly decreased
      as increasing the molar ratio. Also, excellent densification behavior was
      observed when high molar ratio of citric acid to metal nitrate was used. It was
      clarified that the molar ratio of citric acid determines the aggregated particle
      size and, in turn, finial microstructure after sintering.

PMID- 24734635
TI  - Nanofluidic sustainable energy conversion using a 1D nanofluidic network.
AB  - We propose a 1-dimensional (1D) nanofluidic energy conversion device by
      implementing a surface-patterned Nafion membrane for the direct energy conversion
      of the pressure to electrical power. By implementing a -200-nm-thick nano-bridge
      with a 5-nm pore size between two microfluidic channels, we acquired an effective
      streaming potential of 307 mV and output power of 94 pW with 0.1 mM KCI under
      pressure difference of 45 MPa. The experimental results show both the effects of
      applied pressure differences and buffer concentrations on the effective streaming
      potential, and are consistent with the analytical prediction.

PMID- 24734636
TI  - The effect of employing the p/i buffer layers and in-situ hydrogen treatment for
      transparent a-Si:H solar cells.
AB  - In this study, we describe the effects of various thicknesses of triple p/i
      buffer layers and hydrogen treatment on various performances in the fabrication
      of transparent a-Si:H solar cells. For the increment of buffer layer thickness,
      V(oc) increases steadily and J(sc) firstly increases and then decreases. The
      triple buffer layers also enhance the transmittance as well as conversion
      efficiency. For hydrogen plasma treatment, overall performances were enhanced
      with plasma power due to the passivation of dangling bonds at p/i interface.
      Therefore, the usage of triple buffer layers with proper treatment is beneficial
      to obtaining transparent a-Si:H solar cells with high quality.

PMID- 24734637
TI  - Enhanced performance on polymeric light-emitting diode with non-metallic ion in
      the water soluble non-conjugated polymer.
AB  - We have fabricated a polymer light-emitting diode (PLED) from the conventional
      blue-emitting polymer, polyfluorene (PFO), by constructing a multilayer structure
      with non-metal ion containing water soluble non-conjugated polymer, polyurethane
      with F- ion (PU:F-), on the top of the PFO. The device with PU:F- layer shows a
      maximum luminance of 5294 cd/m2 at an applied voltage of 10 V while the one
      without PU:F- layer shows only 4439 cd/m2 at the same applied voltage. We propose
      the improvement of device performance with PU:F- layer was due to not only an
      effective hole blocking at the polymer-polymer interface but also increase of
      electric field strength with anode after electro-stactic repulsion between
      electrons from the cathod and anions from the water soluble polymer layer. We
      will discuss the effect of multilayer polymer structure in PLED in terms of
      current/voltage characteristics, luminance, and quantum efficiency related with
      the applied bias.

PMID- 24734638
TI  - Fabrication of cost-effective surface enhanced Raman spectroscopy substrate using
      glancing angle deposition for the detection of urea in body fluid.
AB  - A surface enhanced Raman spectroscopy (SERS) with glancing angle deposited Ag
      nanorods structures was developed for the detection of urea in human serum. To
      maximize the SERS enhancement, the effects of Ag nanorod length on the SERS
      signal were analyzed. The SERS signals of different concentrations of urea
      solutions were measured in order to generate a regression model for use in
      analyzing the amount of urea in body fluid using the SERS substrate. To examine
      the feasibility of the fabricated SERS substrate, the amount of urea in human
      serum was measured using the SERS substrate and compared with that determined via
      conventional blood analysis.

PMID- 24734639
TI  - Preparation and upconversion emission modification of Yb, Er co-doped Y2SiO5
      inverse opal photonic crystals.
AB  - Yb, Er co-doped Y2SiO5 inverse opal photonic crystals with three-dimensionally
      ordered macroporous were fabricated using polystyrene colloidal crystals as the
      template. Under 980 nm excitation, the effect of the photonic stopband on the
      upconversion luminescence of Er3+ ions has been investigated in the Y2SiO5:Yb, Er
      inverse opals. Significant suppression of the green or red UC emissions was
      detected if the photonic band-gap overlaps with the Er3+ ions emission band.

PMID- 24734640
TI  - Growth and properties of ZnO films grown by the ultrasonic spray-assisted CVD.
AB  - ZnO films were successfully grown on the glass substrates employing an ultrasonic
      spray-assisted CVD method at 573-673 K. The optical properties, electrical
      characteristics and crystalline structures of the films were characterized.
      Effects of the growth temperatures on the film properties were studied. The film
      growth mode, morphology, transmittance, conductivity and emission properties are
      very sensitive to the growth temperatures. Growing at lower temperatures would
      improve both the preferential growth along c-axis and smoothness of the films.
      The conductivity and transmittance of the films grown at 573 K are also superior
      to that grown at higher temperatures. All films exhibit strong emission in the
      visible region and weak emission in UV region. However, the relative intensity of
      the UV emission to visible emission of the film grown at 573 K is obviously
      stronger than that grown at higher temperatures.

PMID- 24734641
TI  - Preparation and photoelectrochemical properties of a self-assembled film based on
      wheel type polyoxomolybdate and hemicyanine derivative.
AB  - A new electrostatically self-assembled film has been successfully prepared on
      quartz and indium-tin-oxide (ITO) coated glass substrates by alternating
      adsorption of a wheel-shaped polyoxomolybdate {Mo154} and a hemicyanine of (E)
      1,1'-methylenebis(4-(4-(dimethylamino)styryl)pyridinium) bromide (H1). The UV
      visible spectra demonstrated that the film was uniform, reproducible, and the H1
      in the film forms the J-aggregation. Photoelectrochemical investigations showed
      that the films can generate stable cathodic photocurrent, and the cathodic
      photocurrent density of three-layer film was 5.1 microA/cm2 while irradiated with
      100 mW/cm2 polychromatic light of 730 nm > lambda > 325 nm at an applied
      potential of -0.3 V versus saturated calomel electrode.

PMID- 24734642
TI  - Dominant factor determining the conduction-type of nitrogen-doped ZnO film.
AB  - Nitrogen-doped zinc oxide (ZnO) film has been grown by molecular beam epitaxy.
      The as-grown sample showed p-type conduction with a hole concentration of 3.1 x
      10(17) cm(-3). After an annealing process in O2 at 600 degrees C for 30 min, p
      type conduction was still remained, and the hole concentration of the film
      decreased to 6.8 x 10(16) cm(-3). Secondary ion mass spectroscopy revealed that
      the concentration of both nitrogen and hydrogen decreased after the annealing
      process. It is demonstrated that the intrinsic compensation source has been
      decreased after the annealing process. Because the variation trend of the hole
      concentration in the ZnO:N film is opposite to that of hydrogen and intrinsic
      defects, but in good accordance with nitrogen, the extrinsically substituted
      nitrogen (N(o)) should be the dominant factor that determines the conduction-type
      of the ZnO:N film.

PMID- 24734643
TI  - Inhibition of water activated by far infrared functional ceramics on
      proliferation of hepatoma cells.
AB  - Rare earth (RE)/tourmaline composite materials prepared by the precipitation
      method are added to the ceramic raw materials at a certain percentage and
      sintered into RE functional ceramics with high far infrared emission features.
      Then the far infrared functional ceramics are used to interact with water. The
      influence of the ceramics on the physical parameters of water is investigated,
      and the effect of the activated water on the growth of Bel-7402 hepatoma cells
      cultured in vitro is further studied. The results indicate that, compared with
      the raw water, the water activated by the ceramics can inhibit the proliferation
      of hepatoma cells, with statistical probability P < 0.01, which means that the
      effect is significant. It can be explained that the water activated by the
      ceramics has a higher concentration of H+, which decreases the potential
      difference across the cell membrane to release the apoptosis inducing factor
      (AIF). After entering the cells, the activated water stimulates the mitochondria
      to produce immune substances that lead tumor cells to apoptosis.

PMID- 24734644
TI  - Cleanability evaluation of ceramic glazes with nanometer far-infrared materials
      using contact angle measurement.
AB  - The cleanability of easy-to-clean ceramic glazes doped with nanometer far
      infrared materials was compared with that of some high-quality household ceramic
      glazes from the market. The cleanability was evaluated by the contact angle
      measurement using a sessile drop method with a Dataphysics OCA-30 contact angle
      analyzer. The results showed that the difference of contact angles of water on
      the glazes before soiling and after cleaning could be used as a parameter for
      evaluating the cleanability of the glazes. The relationship between cleanability
      and surface properties, such as surface free energy and surface topography, was
      investigated. The surface free energy of the samples and their components were
      calculated using van Oss acid-base approach. By measuring advancing and receding
      contact angles, the contact angle hysteresis of the ceramic glazes due to the
      surface topography was investigated. It was shown that the cleanability of
      ceramic glazes containing nanometer far-infrared materials (NFIM) is better than
      that of household ceramic glazes from market, due to a higher ratio of electron
      acceptor parameter to electron-donor parameter, which led to the effect of water
      hydration as well as better hydrophilic property and increased smoothness. The
      contact angle measurement not only accurately evaluates the cleanability of the
      ceramic glazes, but also has a contribution to the study of cleanability theory.
      Moreover, this method is simple, convenient and less sample-consumption.

PMID- 24734645
TI  - Solar-blind photodetector based on LaAlO3 with low dark current.
AB  - In this letter, metal-semiconductor-metal (MSM) solar-blind photodetector was
      fabricated on LaAlO3 (110) substrates with Pt and Au electrodes. The substrate
      material was characterized by XRD and UV-visible absorption spectrum. At 10 V
      bias, the photodetector with Pt electrodes shows a very low dark current of 4.1
      pA, which is much smaller than that of detector with Au electrodes (14.6 pA). The
      low dark current may be attributed to the high density steps and facets on the
      (110) surface as well as the large lattice mismatch at the Pt/LaAlO3 interface.
      The device exhibits a peak responsivity of 32.5 mA/W at 200 nm ultraviolet light,
      which lies in the solar-blind spectral region (200-280 nm). The reasons of low
      dark current and high responsivity, which were important to photodetectors, were
      discussed in detail.

PMID- 24734646
TI  - Upconversion luminescence properties of Yb3+ and Tm3+ codoped amorphous fluoride
      ZrF4-BaF2-LaF3-AlF3-NaF thin film prepared by pulsed laser deposition.
AB  - The Yb3+ and Tm3+ co-doped 55.98ZrF4-28BaF2-2.5LaF3-4AlF3-7NaF-2.5YbF3-0.02TmF3
      amorphous fluoride film was prepared by pulsed laser deposition. The
      spectroscopic properties and energy transfer analysis of this film were studies
      in detail. Ultraviolet and visible upconversion emissions were observed under the
      infrared excitation at 980 nm. In comparison with that of its target, the
      upconversion emissions of the film in the visible and ultraviolet range were
      greatly enhanced. The possible energy transfer mechanism of the emissions was
      given to understand the upconversion process. This kind of thin films has
      potential applications for the integrated optical waveguide amplifier and
      ultraviolet laser.

PMID- 24734647
TI  - Photoluminescence properties and spectral structure analysis of NaLn(MoO4)2:Eu3+
      (Ln = Gd, Y) phosphors.
AB  - In this paper, a facile synthetic route for the preparation of NaLn(MoO4)2:Eu3+
      (Ln = Gd, Y) nanocrystals by a hydrothermal method is reported. The
      NaLn(MoO4)2:Eu3+ (Ln = Gd, Y) micro-powders were synthesized by a high
      temperature solid-state reaction. The optical properties of Eu3+ as a local
      structural probe are analyzed when being incorporated into NaLn(MoO4)2 (Ln = Gd,
      Y) micro-powders and nanocrystals. In NaLn(MoO4)2:Eu3+ (Ln = Gd, Y), the
      substitution of Ln3+ by Eu3+ is confirmed and the point symmetry of the site and
      crystal structure are analyzed. The luminescence mechanism and the size
      dependence of their fluorescence properties in NaLn(MoO4)2:Eu3+ (Ln = Gd, Y)
      micro-powders and nanocrystals are also discussed in detail.

PMID- 24734648
TI  - Enhancement of the short wavelength upconversion emission in inverse opal
      photonic crystals.
AB  - Upconversion luminescence properties of Yb-Tb codoped Bi4Ti3O12 inverse opals
      have been investigated. The results show that the upconversion emission can be
      modulated by the photonic band gap. More significantly, in the upconversion
      inverse opals, the excited-state absorption of Tb3+ is greatly enhanced by the
      suppression of upconversion spontaneous emissions of the intermediate excited
      state, and thus the short wavelength upconversion emission from Tb3+ is
      considerably improved. We believe that the present work will be valuable for not
      only the foundational study of upconversion emission modifications but also new
      optical devices in upconversion displays and short wavelength upconversion
      lasers.

PMID- 24734649
TI  - Preparation and characterization of fucoidan-chitosan nanospheres by the
      sonification method.
AB  - Fucoidan was chosen a substitute for alginate in chitosan-based polyelectrolytes
      or polyiones because it is negatively charged and possesses pharmacological
      properties. The fucoidan-chitosan nanospheres were prepared by the sonification
      method, and different formulation variables were investigated to get regular and
      round microspheres. Single factor and orthogonal experiments were carried out in
      this process, and nanospheres were finally prepared successfully. Stability tests
      revealed that some of the spheres were stable over one week. Combined with the
      drug loading/release profiles when using bovine serum albumin and capecitabine as
      model drugs for peptide and small molecule drug respectively, it can be concluded
      that the nanospheres may have potential applications in drug delivery.

PMID- 24734650
TI  - The photoluminescence properties of CdSe QDs prepared by the one-pot process.
AB  - CdSe quatum dots (QDs) have been prepared through the one-pot process.
      Ultraviolet-visible (UV-vis) absorption and emission spectra were used to
      characterize the resulting samples. The effect of the synthesis time and
      temperature on the optical properties of the CdSe QDs samples have been studied.
      The maximum of the absorption spectra of the CdSe QDs samples is 486 nm and the
      emission spectra is 528 nm. The emission intensity of the CdSe QDs samples
      increases, and the emission maximum presents a red shift with increasing reaction
      time.

PMID- 24734651
TI  - Hydrothermal synthesis and green luminescent properties of Lu2O3:Yb3+/Ho3+
      nanocubes.
AB  - Uniform and dispersive Lu2O3:Yb3+/Ho3+ nanocubes have been successfully
      synthesized by the hydrothermal process followed by a subsequent calcination at
      800 degrees C. X-ray diffraction (XRD), field-emission scanning electron
      microscopy (FESEM), high-resolution transmission electron microscopy (HRTEM),
      photoluminescence (PL), cathodoluminescence (CL) spectra, as well as lifetimes
      measurements were utilized to characterize the synthesized phosphors. The as
      formed RE(3+)-doped lutetium oxide precursor via the hydrothermal process as a
      template could transform to RE(3+)-doped Lu2O3 with their original cubic
      morphology and slight shrinkage in the size after the post-annealing process. The
      formation mechanism for the lutetium oxide precursor cubes has been proposed.
      Under the excitation of UV light, 980-nm laser and low-voltage electron-beams,
      Lu2O3:Yb3+/Ho3+ phosphors all show the characteristic emission of the Ho3+ ion
      (5F4, 5S2 --> 18 transition) withgreen color, which is easily observed by naked
      eyes. The corresponding luminescent mechanisms have been discussed. Due to the
      excellent PL (including up-conversion and down-conversion) properties and CL
      properties of the Lu2O3:Yb3+/Ho3+ phosphors, they are potentially applicable in
      fluorescent lamps, up-conversion fluorescent labels and FED devices as an
      efficient green phosphor.

PMID- 24734652
TI  - Preparation and performance of thermal insulation energy saving coating materials
      for exterior wall.
AB  - Nano zinc oxide with a high refractive index has good thermal reflection
      performance, hollow glass microspheres have good thermal reflection and
      insulation performance, and sepiolite nanofibers with many nanostructural pores
      have good thermal insulation performance. The dispensability of nano zinc oxide
      in coating materials was improved by optimizing surface silane coupling agent
      modification process, leading to the good thermal reflection performance. The
      thermal insulation performance was improved by hollow glass microspheres and
      sepiolite nanofibers. On this basis, the thermal insulation coating materials
      were prepared by exploring the effect of amount, complex mode, and other factors
      of the above three kinds of functional fillers on the thermal reflection and
      insulation performance of coating materials. The results showed that the surface
      modification effect of nano zinc oxide was the best when the silane coupling
      agent addition was 6%. The reflection and insulation performance of the coatings
      were the best when the additions of modified nano zinc oxide, hollow glass
      microspheres, and sepiolite nanofibers were 3%, 4%, and 4%, respectively.
      Compared with the control coating materials, the thermal insulation effect was
      improved obviously, which was evaluated by the -13.5 degrees C increase of
      maximum temperature difference between the upper and the lower surfaces.

PMID- 24734653
TI  - Magnetic and morphological properties of CoCu nanowires.
AB  - Heterogeneous CoCu nanowires containing different amounts of Co (up to 50% at. wt
      of Co) are made by electro-deposition (ED) method. CoCu nanowires were grown in
      AAO templates by varying the current density. The diameter of CoCu nanowires was
      around 40 nm. Therefore, the growing of CoCu nanowires was compacted with the
      diameter of AAO templates. The XRD patterns showed that all the CoCu nanowires
      fabricated via electro-deposition were polycrystalline. At low current density
      (1.32 mA/cm2), the intensity of Cu (111) peak was very strong. Increasing the
      current density can be led to increase the intensity of Co (100) peak. High
      resolution transmission electron microscopy (HRTEM) images of the highest Co
      content (50%at.) wires showed the existence of layers of polycrystalline
      heterogeneous CoCu alternating with layers of Cu. The magnetic properties showed
      that the highest coercivity (7.235 kOe) and squareness (0.754) were found in the
      unannealed nanowires having the highest Co content.

PMID- 24734654
TI  - Growth control of carbon nanotubes using by anodic aluminum oxide nano templates.
AB  - Anodic Aluminum Oxide (AAO) template prepared in acid electrolyte possess regular
      and highly anisotropic porous structure with pore diameter range from five to
      several hundred nanometers, and with a density of pores ranging from 10(9) to
      10(11) cm(-2). AAO can be used as microfilters and templates for the growth of
      CNTs and metal or semiconductor nanowires. Varying anodizing conditions such as
      temperature, electrolyte, applied voltage, anodizing and widening time, one can
      control the diameter, the length, and the density of pores. In this work, we
      deposited Al thin film by radio frequency magnetron sputtering method to
      fabricate AAO nano template and synthesized multi-well carbon nanotubes on a
      glass substrate by microwave plasma-enhanced chemical vapor deposition (MPECVD).
      AAO nano-porous templates with various pore sizes and depths were introduced to
      control the dimension and density of CNT arrays. The AAO nano template was
      synthesize on glass by two-step anodization technique. The average diameter and
      interpore distance of AAO nano template are about 65 nm and 82 nm. The pore
      density and AAO nano template thickness are about 2.1 x 10(10) pores/cm2 and 1
      microm, respectively. Aligned CNTs on the AAO nano template were synthesized by
      MPECVD at 650 degrees C with the Ni catalyst layer. The length and diameter of
      CNTs were grown 2 microm and 50 nm, respectively.

PMID- 24734655
TI  - Preparation and mechanism of nano mullite powders from kaolin via open
      hydrothermal process.
AB  - Nano mullite powders have been synthesized from calcined kaolin via open
      hydrothermal process. The powder product was characterized by X-ray diffraction
      (XRD) analysis, scanning electron microscopy (SEM), transmission electron
      microscopy (TEM) with selected area electron diffraction (SAED) analysis. The
      results indicated that single phase puncheon-shaped nano mullite with about 140
      360 nm in length and 50-80 nm in diameter is produced when synthesized in 4 mol/L
      NaOH solution at 100 degrees C for 4 h. The grain size of mullite decrease
      slightly with increasing reaction time from 0 h to 4 h. In addition, nuclear
      magnetic resonance (NMR) analysis confirms presence of Al3+ during the whole
      reaction process, which indicates that there is an absence of growth units of
      mullite in the open hydrothermal system and the mullite precursor mainly
      underwent a solution process during open hydrothermal treatment.

PMID- 24734656
TI  - Growth and characterization of CdS thin films on polymer substrates for
      photovoltaic applications.
AB  - In this work, cadmium sulfide (CdS) films were deposited on flexible polymer
      substrates such as polycarbonate (PC) and polyethylene terephthalate (PET). The
      r.f. magnetron sputtering, which is cost-effective scalable technique, was used
      for the film deposition. The structural and optical properties of the films grown
      at different sputtering pressures were investigated. When the CdS film was
      deposited at lower pressure, the crystallinity and the preferred orientation
      toward c-axis in hexagonal phase was improved. However, the optical transmittance
      was reduced as the sputtering pressure was decreased. Compared with the glass
      substrate, CdS films grown on polymer substrates were exhibited some wore
      structural and optical characteristics. CdTe thin film solar cell applied to
      sputtered CdS as a window layer showed a maximum efficiency of 11.6%.

PMID- 24734657
TI  - Preparation and characterization of nanosilica from oil shale ash.
AB  - Nano-sized silica powders was prepared using oil shale ash (OSA) as starting
      materials. A combined process was proposed for the utilization of OSA in the
      production of the nanosilica, including three stages: calcination, alkaline
      leaching and carbon dioxide separation. Effects of the calcining temperature,
      sodium hydroxide concentration and holding time on the desilication ratio were
      investigated. The microstructure and morphologies of the nano-sized silica were
      characterized by X-ray diffraction, transmission electron microscopy, and
      Brunauer-Emmett-Teller nitrogen-gas adsorption method. The results indicated that
      the obtained powders with particle size of about 40 nm are homegeneously
      dispersed and its specific surface area is 387 m2/g. The properties of the nano
      sized silica powder meet the requirements of the Chinese Chemical Industry
      Standard HG/T 3061-1999.

PMID- 24734658
TI  - Bioconjugation of poly(acrylic acid)-capped BaYF5:Yb3+/Er3+ up-conversion
      nanoparticles to bovine serum albumin: synthesis and photoluminescent properties.
AB  - Water-soluble BaYF5:Yb3+/Er3+ nanoparticles with the surface functionalized by a
      layer of poly(acrylic acid) (PAA) were synthesized via a facile one-step PAA
      assisted hydrothermal method. Bovine serum albumin (BSA) protein was conjugated
      with BaYF5:Yb3+/Er3+ upconversion nanoparticles via free carboxylic acid groups
      on the surface of nanoparticles. The final products were characterized by X-ray
      diffraction (XRD), transmission electron microscopy (TEM), infrared (IR)
      spectrophotometry, ultraviolet (UV) spectrophotometry and photoluminescence
      spectroscopy (PL). The XRD results showed that PAA-capped BaYF5:Yb3+/Er3+
      upconversion nanoparticles could be obtained via a PAA assisted hydrothermal
      process with the pH value of 8 at 200 degrees C for 24 h. The TEM results showed
      that the morphology of BaYF5:Yb3+/Er3+ nanoparticles was spherical particles with
      an average diameter of about 4 nm. The IR and UV spectra showed that BSA has been
      conjugated with BaYF5:Yb3+/Er3+ up-conversion nanoparticles. The luminescence
      properties of BaYF5:Yb3+/Er3+ up-conversion nanoparticles were also studied. The
      luminescence properties of the products suggest that BaYF5:Yb3+/Er3+ upconversion
      nanoparticles have promising applications for labels in biological assays.

PMID- 24734659
TI  - The size confinement effect for Ln3+ (Ln = Tm or Eu) concentration quenching and
      energy transfer in Y2O3 nanocrystals.
AB  - Y2O3:Ln (Ln = Tm or Eu) nano-powders with different particle sizes and various
      doping concentrations were prepared by using a combustion method. The bulk
      powders doped with the same concentrations were obtained by annealing the nano
      powders at high temperatures. Emission spectra of the phosphors were measured.
      The crystal structure and morphology of the phosphors were characterized by XRD
      (X-ray diffraction) and FE-SEM (field emission scanning electron microscopy),
      respectively. The concentration quenching of luminescent centers and energy
      transfer between luminescent centers in Y2O3:Ln nanocrystal powders were
      investigated. It is found that the behavior of luminescent concentration
      quenching for Eu3+ 5D0 --> 7F2 in nano-powders is similar to that in bulk
      powders. On the contrary, the quenching concentration for Tm3+ 1D2 --> 3H4 is
      distinctly higher than that in bulk powders. This owes to the size confinement
      effect which will restrain the electric dipole-dipole interaction as a long-rang
      interaction (e.g., energy transfer between Tm3+ ions), and will hardly affect the
      exchange interaction which is a short-rang interaction (e.g., energy transfer
      between Eu3+ ions).

PMID- 24734660
TI  - The R-curve behavior and thermal shock resistance for Al2O3 + ZrO2 laminated
      nanoceramics.
AB  - The properties of thermal shock resistances of Al2O3 + ZrO2 monolayer and
      laminated ceramics are determined by the indentation method. The relationships
      between the R-curve, the thermal shock resistance properties and the mechanism of
      strengthening and toughening are also studied in this paper. The Al2O3 + ZrO2
      laminated ceramics have an R-curve feature and a decrease in the sensitivity of
      the strength to the size of surface cracks. Indentation thermal shock test shows
      that the critical temperature difference of the Al2O3 + ZrO2 laminated ceramics
      is 400 degrees C, 150 degrees C higher than that of the monolayer ceramics. Under
      the condition of the surface compressive stress, the surface fracture appearance
      is more uneven and the fracture mechanism is different along the interface. The R
      curve and thermal shock resistance properties are improved by strengthening the
      transformation effect resulting from the surface compressive stress.

PMID- 24734661
TI  - X-ray reflectivity analysis of titanium dioxide thin films grown by cathodic arc
      deposition.
AB  - TiO2 thin films deposited by a vacuum arc on a glass substrate were characterized
      by X-ray reflectivity (XRR), X-ray diffraction (XRD), scanning electron
      microscopy (SEM) and atomic force microscopy (AFM). Several thin films with
      different amounts of deposited TiO2 mass and different deposition and annealing
      temperatures were studied. A qualitative analysis of the XRD patterns indicated
      the presence of the anatase and/or rutile crystalline phases in most of the
      studied samples. From the analysis of the experimental XRR curves--which
      exhibited a wide angular range of oscillatory behavior--the thickness, mass
      density and interface roughness were determined. All XRR patterns were well
      fitted by modeled curves that assume the presence of a single and homogeneous
      TiO2 layer over which a very thin H2O layer is adsorbed. The thickest H2O
      adsorption layers were developed in films with the highest anatase content. Our
      overall results of the XRR analyses are consistent with those derived from the
      imaging techniques (SEM and AFM).

PMID- 24734662
TI  - Alpha-NaYF4:Nd3+ nanocrystal with near-infrared to near-infrared luminescence for
      bioimaging applications.
AB  - Nd3+ doped alpha-NaYF4 nanocrystals with size of about 15 nm were successfully
      synthesized through hydrothermal method. Nearly pure near-infrared to near
      infrared (NIR-to-NIR) luminescence can be realized. Moreover, the excitation and
      the emission at 880 and 1060 nm, respectively, are away from the visible region.
      These are beneficial to deeper tissue penetration and reduced auto-fluorescence.
      This material exhibits an excellent NIR-to-NIR emission performance and is thus
      potentially applicable as a high-contrast in vitro and in vivo imaging probe.

PMID- 24734663
TI  - Electrospinning preparation and luminescence properties of terbium
      complex/polymer composite fibers.
AB  - The terbium complex Tb(acac)2AA (acac: acetyl acetone, AA: acrylic acid) was
      incorporated into polystyrene (PS) matrix and electrospun into various composite
      fibers. The mass ratios of rare-earth complex to polymer were fixed in all
      composite fibers. The diameters of the composite fibers decrease with increase in
      the collection distance during electrospinning. The luminescence properties of
      the Tb(acac)2AA/PS composite fibers were studied in comparison to those of the
      pure Tb complex. The excitation bands became narrower and blue-shifted compared
      with that of the pure complex in all of the Tb(acac)2AA/PS composite fibers. The
      fluorescence lifetime of the 5D4 state of Tb3+ ion in the composite fibers was
      shorter than that of the Tb complex. The effect of the fiber diameter on the
      luminescence properties was also studied. As a result, the fluorescence lifetimes
      of the 5D4 state in all of the Tb(acac)2AA/PS composite fibers decreased
      gradually with decrease in diameter.

PMID- 24734664
TI  - Regulating the formation of self-supported LiCoO2 nanostructure by alkaline
      concentration and study on its electrochemical property.
AB  - LiCoO2 nanosheets with high crystallinity and large area were synthesized via a
      facile hydrothermal route. The structure and morphology properties of the
      nanosheet are identified by powder X-ray diffraction (XRD), transmission electron
      microscopy (TEM), scanning electron microscopy (SEM), Brunauer-Emmett-Teller
      (BET) specific surface area analysis. The experimental results show that the
      morphology and the thickness of the nanosheet can be tuned by simply regulating
      the concentration of the NaOH solution. The higher the NaOH concentration, the
      thinner (less than 100 nm) and larger (up to several microm) the nanosheet
      becomes. Moreover, the electrical properties of the as-designed nanosheet also
      change with the thickness of the nanosheet. The charge-discharge capacity of the
      LiCoO2 nanosheet tends to increase in the thinner nanosheet with a larger surface
      area. We proposed that the reason may be attributed to the accelerated
      intercalation and de-intercalation process of the lithium ion in the nanosheet.

PMID- 24734665
TI  - Band offsets in YSZ/InGaZnO4 heterostructure system.
AB  - The energy discontinuity in the valence band (deltaE(v)) of Y2O3-stabilized ZrO2
      (YSZ)/InGaZnO4 (IGZO) heterostructures was obtained from X-ray photoelectron
      spectroscopy (XPS) measurements. The YSZ exhibited a bandgap of 4.4 eV from
      absorption measurements. A value of deltaE(v) = 0.57 +/- 0.12 eV was obtained by
      using Ga 2P3/2, Zn 2p3/2 and In 3d5/2 energy levels as references. This implies a
      conduction band offset (deltaE(c)) of 0.63 eV in YSZ/InGaZnO4 heterostructures
      and a nested interface band alignment.

PMID- 24734666
TI  - Photoluminescence studies of SiC/SiO2 aloetic-shaped nanowires.
AB  - Room- and variable-temperature photoluminescence from 3C-SiC aloetic-shaped
      nanowires was presented. The SiC nanowires were prepared on Si(100) substrates by
      the reaction of methane with silicon dioxide. Scanning electron microscope (SEM)
      and X-ray diffraction (XRD) are used to characterization the nanowires. A green
      photoluminescence (PL) band centered at 2.34 eV is observed in the nanowires at
      room temperature. The results from variable-temperature photoluminescence show
      anomalous temperature dependencies of the spectral characteristics. The emission
      intensity increases with decreasing temperature until reaching an intensity
      maximum at about 155 K, then it decreases at lower temperatures. The emission
      energy has little shift following temperature variations. The anomalous
      temperature dependencies of PL results may be explained by quantum confinement
      effect and phonon participation in the emission process.

PMID- 24734667
TI  - Photoelectrochemical properties of graphene oxide-based electrostatically self
      assembled film.
AB  - Graphene oxide (GO) and polyethylenimine were successfully assembled into
      ultrathin films by using the electrostatic layer-by-layer self-assembly
      technique. The film assembling process was monitored by ultraviolet-visible
      spectroscopy. A linear increase in the film absorption with the number of
      deposited layers indicated that the (GO/PEI)(n) film depositions were uniform and
      reproducible. The photoelectrochemical properties of these multilayer films were
      investigated in an aqueous Na2SO4 solution, and it was found that the GO(PEI/GO)2
      film exhibited stable cathodic photocurrents.

PMID- 24734668
TI  - Channel microstructure and thermal insulation mechanism of sepiolite mineral
      nanofibers.
AB  - The longitudinal and cross sectional TEM images of sepiolite mineral nanofibers
      were prepared by cutting in the direction parallel and perpendicular to
      nanofibers, and the channel microstructure of sepiolite nanofibers was studied.
      The thermal insulation mechanism of sepiolite nanofibers was analyzed according
      to the diagrammatic sketch obtained from the above experimental method. The
      results showed that many discontinuously connected bending shape channels with
      about 23-26 nm in diameter existed in the center region of nanofibers, and many
      discontinuously connected irregular micropores and mesopores with the size of
      about 1-9 nm existed on the wall of nanofibers. The main reasons for the
      formation of channel microstructure in sepiolite nanofibers were their
      minerogenetic conditions and the interaction between acid and high-speed airflow
      in the process of nanofibers preparation, and bubbles in the hydrotherm played a
      significant role in the microstructure formation. The thermal insulation
      performance of sepiolite nanofibers could be attributed to obstructive and
      infrared radiative thermal insulation.

PMID- 24734669
TI  - Preparation of tourmaline nano-particles through a hydrothermal process and its
      infrared emission properties.
AB  - Tourmaline nano-particles were successfully prepared via a hydrothermal process
      using HCl as an additive. The reaction temperature (T) and the concentration of
      HCI (C(HCl)) had effects on the size and morphology of the tourmaline nano
      particles. The optimum reaction condition was that: T = 180 degrees C and C(HCl)
      = 0.1 mol/l. The obtained nano-particles were spherical with the diameter of 48
      nm. The far-infrared emissivity of the product was 0.923. The formation mechnism
      of the tourmaline nano-particles might come from the corrosion of grain boundary
      between the tourmaline crystals in acidic hydrothermal conditions and then the
      asymmetric contraction of the crystals.

PMID- 24734670
TI  - Facile synthesis and enhanced near infrared luminescent properties of
      CaWO4:Ln3+/Na+ (Ln = Nd, Er, and Yb) core/shell microstructure.
AB  - In this work, we reported the fabrication and characterization of CaWO4:Ln3+/Na+
      (Ln = Nd, Er, and Yb) core/shell microspheres via a facile hydrothermal method in
      the presence of citric acid and PVP. The samples were characterized by X-ray
      diffraction, scanning electron microscopy, transmission electron microscopy,
      infrared spectra, and photoluminescence. It's found that citric acid could
      modulate the nucleation and growth of CaWO4 nanocrystals and enable the co
      incorporation of Na+ and Ln3+ (Ln = Nd, Er, and Yb) into CaWO4 lattice.
      Meanwhile, PVP controlled the assembly of CaWO4 nanocrystals into a core/shell
      spherical structure. All CaWO4:Ln3+/Na+ (Ln = Nd, Er, and Yb) core/shell
      microspheres exhibited intense near-IR luminescence. In comparison with
      CaWO4:Ln3+/Na+ nanocrystals, the self-assembled core/shell nanoarchitechtures
      showed highly enhanced IR luminescent properties due to the depressing of surface
      energy-loss.

PMID- 24734671
TI  - Preparation of ZnO:Eu3+ nanospheres via a micro-emulsion method and analysis of
      the photoluminescence properties.
AB  - ZnO:Eu3+ nanospheres were prepared via a micro-emulsion method with hexadecyl
      trimethyl ammonium bromide as the primary surfactant, butanol as the cosurfactant
      and octane as the oil phase. The X-ray diffraction (XRD) pattern suggests that
      the Eu3+ ions have entered into the ZnO lattices. Scanning electron microscopy
      (SEM) images show that large scale-shaped nanospheres about 200-500 nm in size
      were formed. The photoluminescence (PL) spectra suggest that the Eu3+ ions doped
      into ZnO have located at the non-inversion center positions because only the 612
      nm peak (5D0 --> 7F2) occurred in the emission spectra. A schematic drawing for
      the possible mechanisms of electron transitions in the PL excitation and emission
      spectra is also proposed.

PMID- 24734672
TI  - Hydrothermal synthesis and luminescent properties of SrF2 and SrF2:Ln3+ (Ln = Eu,
      Ce, Tb) nano-assembly with controllable morphology.
AB  - SrF2 and SrF2:Ln3+ (Ln = Eu, Ce, Tb) nano-assemblies with controllable size and
      morphology have been successfully prepared via a facile hydrothermal process. X
      ray diffraction, scanning electron microscopy, and photoluminescence spectrum
      were used to characterize the samples. The experimental results indicate that
      chelating reagent and acidity play important roles in the formation of micro
      crystals with uniform size and peculiar morphology. As-obtained SrF2:Eu3+ and
      SrF2:Ce3+, SrF2:Tb3+ samples show red, ultraviolet and green emission under the
      irradiation of ultraviolet.

PMID- 24734673
TI  - Self-assembly of silver nanoparticles illuminated by a visible-near-infrared
      lamp.
AB  - Silver nanoparticles (NPs) with diameters of 5-10 nm were synthesized by using
      formaldehyde (HCHO) to reduce silver nitrate (AgNO3) and polyethylenemine (PEI)
      as a stabilizer. It was found that on the carbon-supported cupper grid
      (Cu/polyvinylformal (PVF)/C) and under a visible-near-infrared (VIS-NIR, 400-860
      nm) lamp illuminating at about 75 degrees C for six minutes, the spherical Ag NPs
      self-assembled into bigger NPs, triangular nanoprisms, or structures like clock
      hands. On the glass slides, the NPs firstly self-assembled into spherical
      particles with 3-6 microm in sizes, then assembled into chain structures
      comprised of 3-20 spherical particles after being illuminated by the VIS-NIR lamp
      for about nine minutes. The violent thermal motion of the NPs after being
      illuminated by the VIS-NIR lamp leads to the self-assembly and the shapes of the
      self-assembled particles are related to the interactions between the substrates
      and the samples.

PMID- 24734674
TI  - Preparation of zirconia transparent ceramics by low temperature microwave
      sintering.
AB  - Nanocrystalline yttria-stabilized zirconia (ZrO2-8 mol%Y2O3, 8YSZ) was
      synthesized by a homogeneous precipitation process using urea as the
      precipitation agent. Zirconia (ZrO2) transparent ceramics samples have been
      successfully fabricated by a microwave sintering process at low temperature. The
      technologies of low-temperature microwave sintering and the relationships of the
      microstructures and properties of the specified samples have been investigated in
      detail. We have found out that the low-temperature microwave sintering has its
      obvious advantages over the other methods in manufacturing zirconia transparent
      ceramics.

PMID- 24734675
TI  - Facile synthesis of TiO2 microspheres with reactive (001) facets for improved
      photocatalytic performance.
AB  - Anatase TiO2 microspheres with a high percentage of exposed (001) facets were
      synthesized by a template-free hydrothermal method without using concentrated
      hydrofluoric acid. The influence of various experiment conditions, such as
      hydrothermal temperature, acid condition, reaction time, etc., on the morphology
      of the final products was investigated in detail. The formation mechanism of the
      microspheres was deduced according to the XRD, SEM, TEM, and HRTEM
      characterizations. The as-obtained microspheres exhibited superior photocatalytic
      activity in the degradation of Acid Red 88 compared to TiO2 without exposed (001)
      facet.

PMID- 24734676
TI  - A novel method for tinidazole detection using Mn-modified CdSe/CdS quantum dots
      as a luminescent probe.
AB  - A new method for the determination of tinidazole based on the fluorescence
      quenching of citrate-capped Mn-modified CdSe/CdS quantum dots was developed. In
      aqueous solution, the fluorescence of the quantum dots at 610 nm was quenched
      gradually with the increase of the concentration of tinidazole. Based on this, a
      simple, fast, low-cost and specific quantitative method for tinidazole detection
      was set up. Under optimal conditions, a good linearity was built between the
      fluorescence quenching of Mn-modified CdSe/CdS quantum dots and the concentration
      of tinidazole in the range of 4-400 microM with a correlation coefficient of
      0.9998. The limit of detection (3sigma/K) was 0.4 microM. The proposed method was
      applied to the detections of tinidazole in tablets and injections with
      satisfactory results.

PMID- 24734677
TI  - The effect of thin film morphology on the electrochemical performance of Cu-Sn
      anode for lithium rechargeable batteries.
AB  - We investigate the anode performance of non ordered and ordered nanostructured Cu
      Sn thin films deposited via electron beam deposition technique. The ordered
      nanostructured Cu-Sn thin film having nano-porosities was fabricated using an
      oblique (co)deposition technique. Our results showed that the nano structured Cu
      Sn thin film containing Cu-Sn nanorods had higher initial anodic capacity (790 mA
      h g(-)) than that of the non ordered thin film (330 mA h g(-)). But the capacity
      of the ordered nanostructured Cu-Sn thin film diminished after the first cycle
      and a steady state capacity value around 300 mA h g(-) is sustainable in
      following up to 80th cycle, which is attributed to the composition and morphology
      of the thin film. The presence of copper containing Sn nanorods leading to form
      nano-porosities as interstitial spaces among them, enhanced lithium ions movement
      within thin film and increased the thin film tolerance against the stress
      generated because of the drastic volume change occurred during lithiation
      delithiation processes; hence, homogenously distributed porosities increased the
      cycle life of the thin film.

PMID- 24734678
TI  - Electroluminescence emission of crystalline germanium nanoclusters deposited with
      laser assistance at low temperature.
AB  - With CO2 laser assistance, crystalline Ge nanocluster-embedded Ge films were
      deposited at low temperature using a conventional plasma-enhanced chemical vapor
      deposition system. Raman spectrum showed a wavenumber peak at 290 cm(-1) which
      corresponded to the crystalline Ge nanoclusters in the Ge film deposited with CO2
      laser assistance. Crystalline Ge nanoclusters embedded in Ge matrices were
      observed from transmission electron microscopy (TEM) images and electron
      diffraction pattern. The electroluminescent devices constructed with multilayered
      Ge nanoclusters-embedded Ge films were fabricated. The experimental results
      demonstrated that the electroluminescence emission originated from the radiative
      recombination of the electron-hole pairs in the Ge nanoclusters.

PMID- 24734679
TI  - Pauli-Rydberg-London potential: an accurate pair potential function for diatomic
      systems.
AB  - Based on a molecular-orbital theory for H2(+), we have proposed and tested a pair
      potential function form for the diatomic systems. The new form has included the
      Pauli repulsive term, Rydberg potential, and London inverse-sixth-power energy,
      and is accurate at all relevant distances and simple enough for practical
      application in all-atom computer simulations. We find that an "approximate"
      universal reduced potential curve for strongly and weakly bound diatomic
      molecules may exist.

PMID- 24734680
TI  - Entrapment into nanoemulsions potentiates the anticancer activity of tocotrienols
      against the highly malignant (+SA) mouse mammary epithelial cells.
AB  - The highly malignant +SA mouse mammary epithelial cells were used as the model
      cell line over the years to establish the anticancer activity of tocotrienols.
      Tocotrienols, however, have poor oral bioavailability and were therefore
      entrapped into parenteral nanoemulsions for parenteral administration. The
      objective of this work was to test whether the activity of tocotrienols in lipid
      nanoemulsions against the +SA cells was retained. A secondary objective was to
      test whether stabilizing the nanoemulsions with poloxamer or sodium oleate would
      affect their activity. Nanoemulsions were found to be significantly more potent
      than tocotrienol/albumin conjugate. The IC50 values of the poloxamer and sodium
      oleate nanoemulsions were 3 and 6 microM, respectively, whereas the IC50 value of
      the conjugate was 10 microM. The antiproliferative activity of the nanoemulsions
      was also found to inversely correlate with particle size. No activity was
      observed with nanoemulsions loaded with alpha-tocopherol or vehicle, which
      confirmed the cytotoxic activity of tocotrienols and the potential use of
      nanoemulsions in cancer therapy.

PMID- 24734681
TI  - Characterization of polymer based nanocomposites with carbon nanotubes.
AB  - The paper concerns investigation of the processing methods influence on the
      electrical, thermal and mechanical properties of the polymer matrix
      nanocomposites with carbon nanotubes (CNTs) as a filler. The focus is put on the
      relation between microstructure and properties dependently on the parameters of
      mixing, epoxy matrix curing parameters, neat epoxy resin viscosity, carbon
      nanotubes modified with different functional groups, as well as carbon nanotubes
      weight fraction. Nanocomposites with the CNTs varied from 0.05 to 5 wt.% were
      obtained by dispersion methods such as: mechanical stirring, ultrasonication and
      combination both of them, as well as calendaring. Three epoxy resin systems were
      tested, varied in viscosity and curing temperature. Also CNTs nonmodified and
      modified with amino, carboxyl and hydroxyl groups were used. The choice of the
      best epoxy resin system and kind of CNTs for fabrication of conductive
      nanocomposites was done. The lower neat epoxy resin viscosity the better
      dispersion of CNTs can be achieved. The distribution of CNTs in the epoxy matrix
      was evaluated using high resolution scanning electron microscopy, supported by
      image analysis. Electrical conductivity, as well as thermal stability and
      thermodynamic properties of polymers filled with CNTs were determined. Activation
      energy of decomposition process was calculated from thermogravimetric curves by
      Flynn-Wall-Ozawa method. The deterioration of thermal stability was obtained,
      while mechanical properties increase with the CNTs weight fraction growth up to
      0.1%. Calendaring was found as the best method of CNTs dispersion in the polymer
      matrix.

PMID- 24734682
TI  - Synthesis, characterization, and hydrogen storage enhancement of M2(BDC)2dabco
      with palladium-doped activated carbon.
AB  - Two bi-organic type metal organic frameworks (MOFs) such as Co2(BDC)2dabco and
      Zn2(BDC)2 dabco have been synthesized by hydrothermal method and characterized
      along with hydrogen adsorption. The hydrogen adsorption capacity of these MOFs
      was increased after doping by palladium-activated carbon. Co2(BDC)2dabco has
      cracked and folded thin film like surface while Zn2(BDC)2dabco has a brick-typed
      cubic structure with particle size about 10-15 microm identified by FE-SEM. The
      XRD patterns represents that both MOFs have the well crystalline structure.
      Nitrogen adsorption isotherms show that both structures have Type I adsorption
      isotherm with the BET specific surface area of 1,390 and 1,433 m2 g(-1) for
      Co2(BDC)2dabco and Zn2(BDC)2dabco, respectively. Pristine Co2(BDC)2dabco and
      Zn2(BDC)2dabco can store about 0.22 and 0.25 wt.% of H2 measured at 298 K and 32
      bar. This capacity was greatly enhanced by doping palladium-activated carbon to
      0.31 and 0.41 wt.%, respectively. Moreover, both structures were also
      characterized by XANES/EXAFS. EXAFS spectra indicate that Co2(BDC)2dabco has the
      Co--O bond distance of 2.030 A with the coordination number of 4.2 while
      Zn2(BDC)2dabco has 2.015 angstroms bond distance of Zn--O with the coordination
      number of 3.4.

PMID- 24734683
TI  - Synthesis, fine structural characterization, and CO2 adsorption capacity of metal
      organic frameworks-74.
AB  - Two metal organic frameworks of MOF-74 group (zinc and copper-based) were
      successfully synthesized, characterized, and evaluated for CO2 adsorption. The
      both samples such as MOF-74(Zn) and MOF-74(Cu) were characterized with FE-SEM for
      morphology and particle size, XRD patterns for phase structure, FTIR for organic
      functional groups, nitrogen adsorption for pore textural properties, and X-ray
      absorption spectroscopy for fine structural parameters and oxidation states of
      central metal atoms. CO2 adsorption isotherms of MOF-74 samples were measured in
      a volumetric adsorption unit at 273 K and pressure up to 1.1 bar. The MOF-74(Zn)
      and MOF-74(Cu) adsorbents have the pore widths of 8.58 and 8.04 angstroms with
      the BET specific surface areas of 1,474 and 1,345 m2 g(-1), respectively. CO2
      adsorption capacities of MOF-74(Zn) and MOF-74(Cu) were 4.10 and 3.38 mmol x g(
      1), respectively measured at 273 K and 1.1 bar. The oxidation state of central
      atoms in MOF-74(Zn) was Zn(II) confirmed by XANES spectra while MOF-74(Cu) was
      composed of Cu(I) and Cu(II) central atoms. The bond distances of Zn--O and Cu--O
      were 1.98 and 1.94 angstroms, respectively.

PMID- 24734684
TI  - Photocatalytic degradation of reactive red 141 in the presence of Cr(VI) using
      TiO2 nanotubes.
AB  - TiO2 nanotubes were prepared by hydrothermal process, then characterized using
      Brunauer-Emmett-Teller (BET), transmission electron microscopy (TEM), X-ray
      diffraction (XRD) and UV-Visible spectroscopy measurements. The photodegradation
      performance assessment of Reactive Red 141 (RR141) with near visible light
      irradiation (lambda = 380 nm) was carried out under different catalyst doses, dye
      concentrations, pH and initial Cr(VI) concentrations by TiO2 powder and
      nanotubes. The results showed that the specific surface area of TiO2 nanotubes
      were 152 m2 g(-1), about three times larger than that of TiO2 powder which was
      roughly 51 m2 g(-1). The TiO2 nanotubes did not affect the lattice structure of
      the TiO2. The adsorption amount increases as the dosage and RR141 concentration
      increases. However, the decolonization efficiency decreased with increasing
      initial RR141 concentration. Results also showed that an acidic solution is more
      favorable for photocatalytic degradation of RR141. On the other hand, Cr(VI) can
      be adsorbed on the surface of TiO2 nanotubes to affect the decolonization
      efficiency of RR141.

PMID- 24734685
TI  - Photocatalytic studies of crystal violet dye using mn doped and PVP capped ZnO
      nanoparticles.
AB  - Mn (0.5%, 1%, 1.5% and 2%) doped and undoped ZnO nanoparticles (NPs) capped with
      PVP (1.0%) were successfully synthesized via co-precipitation approach using zinc
      acetate, sodium hydroxide and manganese acetate as precursors. Structural
      analysis was performed by XRD confirming phase purity and crystalline wurtzite
      structure. TEM results show average particle size 15-20 nm and 22-25 nm for Mn
      (1%) and Mn (2%) doped ZnO NPs respectively. Manganese (Mn) doping has led to
      reduction in band gap which facilitate the absorption of radiation in visible
      region. The Photocatalytic activity of undoped and Mn (0.5%,1%,1.5% and 2%) doped
      NPs was analyzed via degradation of crystal violet (CV) dye. The crystal violet
      decomposition rate of undoped and Mn doped NPs were studied under UV-visible
      region. It is observed from degradation studies that the doping has a pronounced
      effect on the photocatalytic activity of ZnO NPs. Kinetic studies shows that
      photo degradation of CV follow a pseudo first-order kinetic law. Experiments for
      reusability of Mn (1%) doped with PVP (1%) capped ZnO were also performed to
      determine the stability of as prepared sample. It shows an increase in catalytic
      activity of NPs by small amount when exposed to UV irradiation for 3 h.
      Photoluminescence and UV-Visible absorption spectroscopy studies were also
      performed for studying the effect of UV irradiation on the surface of ZnO NPs.

PMID- 24734686
TI  - Study on the degradation of the dye wastewater with polyaniline on titanium
      nanotubes.
AB  - Polyaniline/titanium nanotube composite (PANI/TNT) photocatalysts were prepared
      by 'in situ'chemical oxidative polymerization of aniline. Transmission electron
      microscopy (TEM), X-ray diffraction (XRD), Fourier transform IR spectra (FTIR)
      and UV-Visible spectroscopy measurements were used to characterize the obtained
      photocatalysts, and their photocatalytic activities were investigated by
      degrading Reactive Green19 (RG19) under near visible light irradiation (lambda =
      365 nm). The content of PANI, pH, dosage, and concentration of RG19 were also
      investigated. The results showed that the inner diameter of the PANI/TNT was 6 nm
      and that the PANI did not change the structure of the TNT. The PANI was coated on
      the surface of the TNT. The light response of the PANI/TNT was extended to the
      visible-light regions. Among the six different kinds of photocatalysts, the 1.17
      wt% PANI/TNT had the best performance in treating 10 ppm RG19. The best pH is 3
      for the largely protonated surface of the composite at low pH. The adsorption
      amount was increased as the dosage increased. The decolonization efficiency
      decreased with increasing initial RG19 concentration. The performance of the
      photocatalyst in decomposing RG19 was stable after 5 time cycles.

PMID- 24734687
TI  - Extended vapor-liquid-solid growth of silicon carbide nanowires.
AB  - We developed an alloy catalytic method to explain extended vapor-liquid-solid
      (VLS) growth of silicon carbide nanowires (SiC NWs) by a simple thermal
      evaporation of silicon and activated carbon mixture using lanthanum nickel
      (LaNi5) alloy as catalyst in a chemical vapor deposition process. The LaNi5 alloy
      binary phase diagram and the phase relationships in the La-Ni-Si ternary system
      were play a key role to determine the growth parameters in this VLS mechanism.
      Different reaction temperatures (1300, 1350 and 1400 degrees C) were applied to
      prove the established growth process by experimentally. Scanning electron
      microscopy and transmission electron microscopy studies show that the crystalline
      quality of the SiC NWs increases with the temperature at which they have been
      synthesized. La-Ni alloyed catalyst particles observed on the top of the SiC NWs
      confirms that the growth process follows this extended VLS mechanism. The X-ray
      diffraction and confocal Raman spectroscopy analyses demonstrate that the
      crystalline structure of the SiC NWs was zinc blende 3C-SiC. Optical property of
      the SiC NWs was investigated by photoluminescence technique at room temperature.
      Such a new alloy catalytic method may be extended to synthesis other one
      dimensional nanostructures.

PMID- 24734688
TI  - Coupled molecular dynamics-stochastic model for thermal conductivity of ethylene
      glycol based copper nanofluid.
AB  - A coupled molecular dynamics (MD)-stochastic simulation based model has been
      proposed here for the thermal conductivity of ethylene glycol (EG) based copper
      nanofluid. The model is based on the thermal evolution of the nanoparticles
      dispersed in the nanofluid which is in contact with a heat source. It is natural
      that the nanoparticles dispersed in the nanofluid would move randomly by Brownian
      motion and repeatedly collide with the heat source. During each collision the
      nanoparticles would extract some heat by conduction mode from the heat source and
      this heat would be dissipated to the base fluid during Brownian motion by a
      combination of conduction and microconvection mode. Thus, in addition to normal
      conductive heat transfer through the base fluid (EG) itself (without
      nanoparticles) some amount of heat is transferred by the collision of the
      nanoparticles with the heat source. The extent of this additional heat transfer
      has been estimated in the present model to estimate the enhancement in thermal
      conductivity of EG based copper nanofluid, as a function of volume fraction
      loading of nanoparticles. The prediction of the present model has been compared
      with the experimental data available in literature, and it has shown a reasonable
      agreement between the theoretical prediction and the experimental data.

PMID- 24734689
TI  - Preparation and characterization of amorphous solid dispersions of nimesulide in
      cyclodextrin copolymers.
AB  - A study to enhance the dissolution rate of nimesulide (NIM), a poorly water
      soluble, non-steroidal anti-inflammatory drug, was carried out through developing
      new amorphous solid dispersions (ASD) based on soluble or insoluble water
      cyclodextrin copolymers (alpha-cyclodextrin, beta-cyclodextrin and y-cyclodextrin
      polymers) synthesized by direct melt polycondensation. Amorphous solid
      dispersions of NIM in cyclodextrin copolymers, obtained by solvent evaporation,
      were characterized by thermogravimetric analyzer (TGA), differential scanning
      calorimetry (DSC), powder X-ray diffraction (PXRD) and fourier transform-infrared
      spectroscopy (FT-IR). These analyses provided the existence of interactions
      between amorphous drug and its carrier. A burst release of more than 80% NIM
      within approximately 70 minutes was seen with soluble alpha-cyclodextrin polymers
      (poly-alpha-sol) and insoluble gamma-cyclodextrin polymers (poly-gamma-insol)
      where no significant differences were observed with the other copolymers.
      Mathematical kinetic models such as zero order, Higuchi and Korsmeyer-Peppas were
      used to evaluate the kinetic and mechanism of release of NIM from the different
      ASD compared to lactose reference matrix. The kinetic of release of NIM from
      different ASD followed a Higuchi model and the mechanism of release was explained
      by Korsmeyer-Peppas model in which a fickian diffusion for lactose and soluble
      beta-cyclodextrin polymers (poly-beta-sol) was observed. However, an anomalous
      non-Fickian transport was found for the other copolymers.

PMID- 24734690
TI  - Gaussian beam incident on the one-dimensional diffraction gratings with the high
      K metal gate stack structures.
AB  - Optical scatterometry has attracted extensive interest in extracting the
      geometric shape information of nanolithography patterns because of the trend of
      shrinking device size and complicated stack structure. RCWA is the numerical
      algorithm implemented in the current scatterometry tool to calculate the
      diffraction efficiency. However, the known weakness for the RCWA method is the
      analysis of metallic gratings illuminated by the TM wave. This research applies
      the FDTD method using the Gaussian beam excitation source to analyze the
      diffraction efficiency of HKMG gratings for the use in the optical scatterometry
      and verifies the numerical diffraction efficiency discrepancy between the
      Gaussian beam and plane wave excitation methods. The numerical study is carried
      out with the line/space nanolithography patterns on the HKMG process stacks at 45
      nm node technology. The nanolithography patterns are modeled as 1-D surface
      relief gratings. The 0th order diffraction efficiency is analyzed as a function
      of CDs, SWAs, incident angles and pitches of the gratings. The study presents the
      impact of the polarizations of the incident waves on the diffraction efficiency.
      In addition, this research investigates the phase of the 0th diffraction order as
      a function of the SWAs and illustrates the corresponding SWA parameter effect on
      the phase distribution. This research suggests the minimum beam radius to
      converge the numerical diffraction efficiency using Gaussian beam excitation to
      it using the plan wave.

PMID- 24734691
TI  - Gold nanoparticles incorporated 3-(trimethoxysilyl)propyl methacrylate modified
      electrode for non-enzymatic electro-sensing of urea.
AB  - We describe non-enzymatic electrochemical sensor for urea based on the
      electrocatalytic activity of gold nanoparticle (AuNPs) incorporated in 3
      (Trimethoxysilyl)propyl methacrylate (TMSPMA) network. AuNPs incorporated in
      TMSPMA network on poly crystalline gold electrode show excellent electrocatalytic
      activity towards urea sensing. Uniform distribution and interaction of Au
      nanoparticles in nanospace of TMSPMA network are probably the key factors for
      catalytic effect of the nanocomposite. Nanocomposite is characterized by UV
      visible diffuse reflectance spectroscopy, cyclic voltammetry, field emission
      scanning electron microscopy and X-ray photoelectron spectroscopy before using as
      urea sensor. The sensing platform is found to be highly sensitive and shows
      linear response in wide range for urea concentration with a sensitivity of 1.13
      microA/microM and limit of detection as 2.08 microM respectively at S/N (signal
      to-noise ratio): 3. It is also observed that the sensor does not suffer
      interference from phosphate and sulphate ions. Further, a possible mechanism for
      electro-sensing of urea with modified electrode has also been proposed.

PMID- 24734692
TI  - Benchtop fabrication of memristive atomic switch networks.
AB  - Recent advances in nanoscale science and technology provide possibilities to
      directly self-assemble and integrate functional circuit elements within the
      wiring scheme of devices with potentially unique architectures. Electroionic
      resistive switching circuits comprising highly interconnected fractal electrodes
      and metal-insulator-metal interfaces, known as atomic switch networks, have been
      fabricated using simple benchtop techniques including solution-phase electroless
      deposition. These devices are shown to activate through a bias-induced forming
      step that produces the frequency dependent, nonlinear hysteretic switching
      expected for gapless-type atomic switches and memristors. By eliminating the need
      for complex lithographic methods, such an approach toward device fabrication
      provides a more accessible platform for the study of ionic resistive switches and
      memristive systems.

PMID- 24734693
TI  - Zr mesoporous molecular sieves as novel solid acid catalysts in synthesizing
      nitrile and caprolactam.
AB  - Zr mesoporous materials with different Si/Zr ratio were synthesized by the
      surfactant-templated method involving cetyl trimethyl ammonium bromide (CTAB) as
      template and tetraethyl ortho silicate (TEOS) as organic source of silicon. The
      synthesized materials were labeled as SiZrMx (where x is Si/Zr = 10, 20 and 30).
      The BET analysis showed bimodal distribution of pores in SiZrMx structure. An
      attempt was made to generate super acidity on SiZrM20 by sulfation using sulfuric
      acid and ammonium sulfate (wt% = 4, 8 and 12). The NH3-TPD results revealed the
      presence of strong acidity in sulfated Zr-MCM-41. To understand the nature of
      acidity in Sulfated Zr-MCM-41, the efficiency of the materials is investigated in
      dehydration of Oximes. The industrially important materials caprolactam and
      intermediate nitrile were synthesized from their oximes in liquid phase system.
      Due to strong acidity in sulfated Zr-MCM-41, fast deactivation was observed
      during the synthesis of caprolactam but, the catalyst showed 96% nitrile
      selectivity. The strong acidity and medium strong acidity favoured the formation
      of nitrile and caprolactam respectively. This study revealed the molecular sieves
      were effective and eco-friendly solid acid catalysts for synthesizing caprolactam
      and nitrile.

PMID- 24734694
TI  - Cationic Poly-L-Lysine-Fe2O3/SiO2 nanoparticles loaded with small interference
      RNA: Application to silencing gene expression in primary rat neurons.
AB  - The cationic PLL-Fe2o3/SiO2-siRNA nanoparticles with an average crystallite size
      of about 20 nm were prepared and delivered into primary rat neurons for knockdown
      of gene expression. Primary rat fetal neurons were scratched to simulate the
      injury of central nervous system and then were transfected with PLL-Fe2O3/SiO2
      siRNA nanoparticles. Optical microscopy, fluorescence microscopy, Western
      blotting, immunofluorescence, and MTT assays were employed to test the
      cytotoxicity, the efficiency of encapsulation and targeted gene silencing. The
      results indicated that the PLL-Fe2O3/SiO2-siRNA nanoparticles have a remarkable
      efficiency of encapsulation and targeted gene silencing with negligible
      cytotoxicity. It could be concluded that the PLL-Fe2O3/SiO2 nanoparticles are a
      promising delivery carrier of siRNA.

PMID- 24734695
TI  - Transparent conductive multiwall carbon nanotubes-polymer composite for electrode
      applications.
AB  - Disperse Multiwall carbon nanotubes (MWCNTs) are incorporated aqueous N-hydroxy
      methyl acrylamide, which is subjected to crosslinking to develop a transparent
      conductive composite free standing film. The effects of the concentration of
      MWCNTs and temperature on optical and electrical properties of nano-composites
      are investigated. Interestingly, only 0.06 mg/ml of MWCNTs is sufficient to reach
      the percolation threshold (Phi) for transition in electrical conductivity up to
      10(-4) S/cm, with a visible transmittance over 85%, which is well above the
      reported for such a low level of MWCNTs loading. The electrical conductivity of
      the composite was measured at 120 degrees C. It has been observed that electrical
      conductivity increases significantly with the increase in temperature, signifying
      the semiconducting nature of nano-composites. Finally, current-voltage (I-V)
      characteristics show liner behaviour, confirms Ohmic nature of nano-composites
      and metal contact.

PMID- 24734696
TI  - Poly(3-hexylthiophene) (P3HT)/graphene nanocomposite material based organic field
      effect transistor with enhanced mobility.
AB  - The major drawback of organic field effect transistors (OFETs) is its lower
      mobility, which restricts their applications for high performance devices.
      Recently, graphene exhibits excellent carrier mobility, therefore, is used as a
      novel electronic substance for the fundamental research and several potential
      applications. Pristine graphene is not applicable in field effect transistors
      (FETs) for satisfactory on/off current ratio as it has no forbidden energy gap.
      Here, we report the fabrication as well as characterizations of poly-3
      hexylthiophene (P3HT)/graphene nanocomposite (with two distinct concentrations
      i.e., 0.05 and 0.1 mg/ml of graphene in P3HT solution) based FETs to over come
      the limitations. The current-voltage (I-V) characteristics of P3HT/graphene based
      FETs are measured and key performance parameters of device are compared against
      only polymer P3HT based FETs. The analysis demonstrates that, in P3HT/graphene
      transistors some crucial parameters such as drain saturation current and mobility
      enhanced drastically although the on/off ratio reduced significantly. Our study
      demonstrates that presence of graphene in organic semiconductor and a synergic
      effect due to uniform distribution in the nanospace is an ordinary route to
      achieve high mobility OFETs which impart an affordable way for raising the
      performance of organic transistors.

PMID- 24734697
TI  - Nano-porous TiO2 layer using ultrafine nano-particles for the blocking layer in
      dye-sensitized solar cells.
AB  - A nano-porous TiO2 layer was produced by spray-deposition using ultrafine anatase
      nano-particles for the blocking layer for the dye-sensitized solar cells (DSCs).
      The microstructure and the electrochemical properties of the spray-deposited TiO2
      layer were examined. The results of electrochemical properties showed that the
      spray-deposited TiO2 layer was capable to suppress the I3- ions diffusion to FTO
      substrate, reducing the electron recombination between the electrons on FTO
      substrate and I3- ions in electrolyte. In addition, the connection between TiO2
      film and FTO substrate was improved by the TiO2 layer. Therefore, the short
      circuit current density and thereby the photo-to-electric energy conversion
      efficiency were improved by this blocking layer. The blocking effect of the
      porous layer was attributed to both the complicated pore structure of the spray
      deposited layer and the enhanced connections between TiO2 film and FTO substrate.
      The low temperature characteristic of spray deposition approach indicates that it
      is suitable to the flexible-based DSCs.

PMID- 24734698
TI  - Multi-branched CdSe nanocrystals stabilized by weak ligand for hybrid solar cell
      application.
AB  - In this article, multi-branched CdSe nanocrystals were produced by a facile
      colloidal approach stabilized by oleylamine at a relative low temperature. The as
      prepared multi-branched CdSe nanocrystals after simple washing process were used
      in the fabrication of poly(3-hexylthiophene)/CdSe bulk heterojunction
      photovoltaic device. The effective charge separation in the poly(3
      hexylthiophene)/ CdSe nanocomposites have been confirmed by the strong
      photoluminescence quenching. The films of the blends of P3HT and simply-washed
      CdSe nanocrystals show more uniform morphology and flatter surface than the film
      of the bends of P3HT and pyridine-refluxed CdSe nanocrystals. The corresponding
      power conversion efficiency under 1 sun is about 0.66% for the P3HT/pyridine
      washed CdSe hybrid device. Our work did a preliminary study in the hybrid solar
      cell application of branched blenze CdSe nanocrystals prepared by an easier way,
      and will be interesting and helpful for making the high-efficiency hybrid solar
      cells with branched CdSe acceptors.

PMID- 24734699
TI  - Modelization of nanospace interaction involving a ferromagnetic atom: a spin
      polarization effect study by thermogravimetric analysis.
AB  - Ab initio studies of ferromagnetic atom interacting with carbon nanotubes have
      been reported in the literature that predict when the interaction is strong, a
      higher hybridization with confinement effect will result in spin polarization in
      the ferromagnetic atom. The spin polarization effect on the thermal oxidation to
      form its oxide is modeled here for the ferromagnetic atom and its alloy, as the
      above studies predict the 4s electrons are polarized in the atom. The four models
      developed here provide a pathway for distinguishing the type of interaction that
      exists in the real system. The extent of spin polarization in the ferromagnetic
      atom has been examined by varying the amount of carbon nanotubes in the
      composites in the thermogravimetric experiments. In this study we report the
      experimental results on the CoNi alloy which appears to show selective spin
      polarization. The products of the thermal oxidation has been analyzed by Fourier
      Transform Infrared Spectroscopy.

PMID- 24734700
TI  - SiO/Carbon complex produced by carbothermal reduction for the anode materials of
      high-performance lithium ion battery.
AB  - SiO/carbon complexes were prepared by electrospinning and carbothermal reduction
      to improve the rate performance at a high C rate, and their electrochemical
      properties were investigated for use as an anode material in a lithium ion
      battery. The SiO/carbon complexes that were prepared by electrospinning had a
      fibrous structure with considerable beads. The crystal structure, composition,
      and surface chemical composition of the SiO/carbon complexes changed based on the
      carbothermal reduction temperature. The SiO/carbon complexes were a mixture of
      SiO2, PAN-based carbon, and beta-SiC. SiC crystal structures and C--Si--O or Si-
      C bonds formed from the reaction of SiO2 and PAN in the SiO2/PAN complex during
      carbothermal reduction above 1,500 degrees C. The charge-discharge profiles of
      these SiO/carbon complexes were similar to those observed for disordered carbon.
      The second discharge capacities and rate capabilities of the SiO/carbon complexes
      were higher than those of graphite. These results were based on reversible
      lithium insertion into and extraction from a silicon material, such as amorphous
      SiO2 or Cx--Si--Oy.

PMID- 24734701
TI  - Probing commensurate ground states of Josephson vortex in layered
      superconductors.
AB  - Because of the commensurability condition between the vortex lattice constant
      determined by external magnetic field and the nano-scale layered structure,
      interlayer Josephson vortices (JVs) in high-Tc cuprate superconductors can take
      various configurations. We have simulated with Langevin scheme the in-plane flux
      flow dynamics of JVs subject to point-like pinning centers. Oscillation in
      resistivity is found with the applied magnetic field, where the resistivity peaks
      occur around commensurate JV configurations. We have also measured the
      resistivity experimentally using single crystals of underdoped YBa2Cu3Oy with the
      anisotropy parameter gamma approximately equal to 50. A unique JV lattice has
      been detected for the first time.

PMID- 24734702
TI  - Selective oxidation of cyclohexane using Ce1-xMnxO2 nanocatalysts.
AB  - The Ce1-xMnxO2 nanocatalysts (x = 0.25, 0.50 and 0.75 wt.%) were synthesized by
      sol-gel method. The catalysts were characterized using various techniques such as
      XRD, N2 sorption study, DRSUV-Vis, TPR, SEM and TEM. The incorporation of Mn ions
      into the ceria lattice was confirmed by XRD analysis. DRUV-Vis spectra confirm
      the presence of Ce3+ ions in the lattice of Ce1-xMnxO2. H2-TPR study revealed the
      oxygen storage capacity of the catalyst. The 3D flowerlike morphology of the
      nanocatalysts was confirmed from FESEM and HRTEM images. The catalytic activity
      was tested for the vapor phase oxidation of cyclohexane using air as an oxidant.
      The key reaction parameters were varied to study the stability, activity and
      selectivity of the catalysts. The study concluded that suitable amount of
      manganese content is essential for the selective oxidation of cyclohexane at low
      temperature and Ce0.25Mn0.75O2 is the most suitable catalyst for high conversion
      and selectivity under the given reaction conditions. The activity of the catalyst
      is correlated with the characterization results.

PMID- 24734703
TI  - Mesoporous iron oxide nanofibers and their loading capacity of curcumin.
AB  - Mesoporous iron oxide nanofibers were obtained by calcination of electrospun
      precursors at various temperatures. Their microstructure is influenced by the
      calcination temperature. As the calcination temperature is at 350 degrees C, the
      resultant iron oxide nanofibers largely consist of magnetic Fe3O4 and gamma
      Fe2O3, with a specific surface area of about 120 m2/g and magnetization of about
      66.5 Am2/kg. When the precursor calcined at 450 degrees C, the pure mesoporous
      alpha-Fe2O3 nanofibers with a specific surface area of about 92 m2/g are obtained
      and they show a high loading for curcumin. All the adjusted R-squares for the
      pseudo-second-order model overtop 0.99 in the initial curcumin ethanol solution
      concentrations of 30, 40 and 60 microg/mL, which suggests the pseudo-second-order
      kinetics model fit the adsorption kinetics of curcumin onto the mesoporous alpha
      Fe2O3 nanofibers, and the adsorption can reach equilibrium in 60 min. While,
      Langmuir model (R2 = 0.9980) fits well the curcumin adsorption isotherm onto
      alpha-Fe2O3 mesoporous nanofibers, and the adsorption capacity is up to 12.48
      mg/g at the curcumin concentration of 60 microg/mL.

PMID- 24734704
TI  - Three-layer structure microwave absorbers based on nanocrystalline alpha-Fe,
      Fe0.2(Co0.2Ni0.8)0.8 and Ni0.5Zn0.5Fe2O4 porous microfibers.
AB  - The three-layer structure microwave absorbers with thickness of 2 mm were
      designed based on nanocrystalline alpha-Fe, Fe0.2(Co0.2Ni0.8)0.8 and
      Ni0.5Zno.sFe204 porous microfibers with diameters about 2-5 microm. The
      electromagnetic parameters and microwave absorption properties were investigated
      by vector network analyzer in the frequency range of 2-18 GHz. The results show
      that the three-layer structure microwave absorbers display stronger absorption
      properties in a wide frequency range than the single-layer and double-layer
      microwave absorber. For the three-layer structure, the microwave absorption
      properties are mainly influenced by the microfibers layer arrangement order,
      total thickness and each layer thickness. When the Ni0.5Zn0.5Fe2O4 porous
      microfibers layer is arranged as the impedance-matching surface layer, with a
      total thickness of 2 mm consisting of 0.7 mm thick alpha-Fe porous microfibers
      inner layer, 0.9 mm thick Fe0.2(Co0.2Ni0.8)0.8 porous microfibers medium layer
      and 0.4 mm thick impedance-matching surface layer, the three-layer structure has
      a strongest microwave absorption of 45.7 dB at 12.8 GHz, the absorption bandwidth
      (with RL < -10 dB ) of 10.2 GHz from 7.8 GHz to 18 GHz and bandwidth (with RL < 
      20 dB) of 4.4 GHz from 11.1 GHz to 15.5 GHz respectively. This three-layer
      structure is promising microwave absorbers to meet the requirements of thin
      thickness, light weight and wide band for military and civil applications.

PMID- 24734705
TI  - Cr-Si Schottky nano-diodes utilizing anodic aluminum oxide templates.
AB  - We have fabricated Cr nanodot Schottky diodes utilizing AAO templates formed on n
      Si substrates. The diameters of the diodes were 75.0, 57.6, and 35.8 nm. Cr
      nanodot Schottky diodes with smaller diameters yield higher current densities
      than those with larger diameters due to an enhanced tunnel current contribution,
      which is attributed to a reduction in the barrier thickness. The diameters of Cr
      nanodots smaller than the Debye length (156 nm) play an important role in the
      reduction of barrier thickness. Also, we have fabricated Cr-Si nanorod Schottky
      diodes with three different lengths (130, 220, and 330 nm) by dry etching of n-Si
      substrate. Cr-Si nanorod Schottky diodes with longer nanorods yield higher
      reverse current than those with shorter nanorods due to the enhanced electric
      field, which is attributed to a high aspect ratio of Si nanorod.

PMID- 24734706
TI  - Photophysical properties and biocompatibility of Photoluminescent Y2O3:Eu
      nanoparticles in polymethylmetacrylate matrix.
AB  - In this study, we produced europium-doped yttoria (Y2O3:Eu) nanoparticles and
      investigated their photoluminescent properties and biocompatibility. The Y2O3:Eu
      nanoparticles showed excellent photoluminescent properties and cytocompatibility.
      We also analyzed the photophysical properties of the nanoparticles in PMMA films.
      When the Y2O3:Eu nanoparticles were incorporated in the polymer film, they showed
      a strong red emission spectrum, similar to that seen with the particles alone.
      Energy dispersive X-ray spectroscopy (EDS) measurements indicated that the
      particles were distributed homogeneously in the PMMA film. Such materials could
      be applied not only to optoelectronic devices but also to biomedical applications
      such as bioimaging tools or luminescent medical/dental adhesive materials.

PMID- 24734707
TI  - The size control of nano-cluster formed on an inorganic nanosheet/cationic
      organic molecule hybrid Langmuir-Blodgett film.
AB  - Organic molecules adsorbed on an inorganic nanosheet often form a nanometer-sized
      cluster. In this study, we propose novel strategy for controlling the cluster
      size. We fabricated hybrid Langmuir-Blodgett (LB) films consisting of N-n
      octadecyl-4-[2-(4-dimethylaminophenyl)ethenyl]-pyridinium bromide and a clay
      mineral, sodium montmorillonite, with varying subphase temperature. As a result,
      the size of the clusters was found to be decreased from 300 nm to 50 nm by
      increasing the subphase temperature from 10 degrees C to 40 degrees C.

PMID- 24734708
TI  - A two-dimensional network of Au nanoclusters on water surface: example of facile
      control of nanospace.
AB  - We report isotherm and Brewster Angle Microscopy (BAM) studies on mixed
      monolayers of Stearic Acid (StA) and Dodecanethiol-capped gold nanoparticles
      (AuNPs) (10% by weight) at the air-water interface. The surface pressure-specific
      molecular area isotherm for the mixed monolayer shows small hysteresis as well as
      a lowering of the slope change in going from L2-L2' and L2'-S phases, indicating
      lesser number of monolayer phases for the mixed film relative to a pristine StA
      monolayer. The BAM study shows formation of a two-dimensional, stable,
      reproducible, and extensive network of nanoparticle clusters with near-circular
      pores, in the 5-20 mN/m surface pressure range. This assembly of nanospaces has a
      pore area peak at approximately 75 microm2, width approximately 120 microm2 and
      can be disassembled and reassembled simply by changing the surface pressure.

PMID- 24734709
TI  - Effects of coating materials on two dimensional stress-induced deflection of
      nanomechanical sensors.
AB  - Nanomechanical sensors, which have been expected as a promising platform for
      various applications, will not generate any measureable signal without an
      appropriate coating (receptor) layer. In spite of this critical dependence on the
      coating layer, there is almost no guideline for the optimization of these layers
      in terms of their material properties; such as, Young's modulus, Poisson's ratio,
      and geometrical parameters. In the present study, the effects of coating layer
      thickness [3 nm-10 microm], Young's modulus [100 Pa to approximately 1 TPa], and
      Poisson's ratio [0.10 to approximately 0.45] are investigated with the finite
      element analysis (FEA), focusing on systems with two dimensional (2D) stress
      induced either on top of the coating layer (i.e., surface stress) or at the
      interface between the coating layer and the silicon cantilever. It is found that
      the coating layer can either enhance or reduce the deflection of nanomechanical
      sensors depending on its material properties. These results provide guidelines
      for designing a coating layer to achieve higher sensitivity.

PMID- 24734710
TI  - Vertical growth of core-shell III-V nanowires for solar cells application.
AB  - High density (In)GaAs/GaAs/AIGaAs nanowires (NWs) consisting of n-type core and p
      type shell have been vertically grown on (111) GaAs substrate using metal organic
      chemical vapor deposition (MOCVD) and fabricated into solar cells. Au colloidal
      nanoparticles (NPs) are employed as a catalyst. High density nanowires were
      obtained by uniform distribution of Au NPs. Fe-SEM, TEM and HRTEM images show
      that the morphology of shell is sensitive to p-doping concentration. Increase in
      the density of p-doping precursor results in "kinking" of NPs and rough shell
      surface. The origin of kinking has been explained by the GaAs twin phases due to
      Zn segregation on the surface of shell. It has been observed that the morphology
      of NPs can be controlled through optimizing various source purge technique of
      DEZn and deposition temperature. Electrical properties of core-shell doped NWs
      are carried out using I-V characterization. The core-shell NWs show
      characteristics of p-n junction as revealed by I-V studies.

PMID- 24734711
TI  - Preparation of La1-xKxFeO3 microtubes and their adsorption kinetics of methyl
      blue.
AB  - The nanocrystalline La1-xKxFeO3 (x < or = 0.2) microtubes with a high specific
      surface area were prepared by the citrate-gel and thermal transformation process.
      These microtubes were characterized by X-ray diffraction (XRD), Brunauere-Emmette
      Teller method (BET), and field emission scanning electron microscopy (FE-SEM).
      With the increase in K content (x) from 0 to 0.2, the average grain size
      decreases from 32.4 to 24.4 nm, and the specific surface area increases from 8.9
      to 36.4 m2/g. The adsorption of methyl blue was analyzed by UV visible
      spectrophotometer. The adsorption capacity increases with the increase of the
      substituted-K content and the surface area of the La1-xKxFeO3 microtubes. The
      adsorption results shows that all the La1-xKxFeO3 microtubes exhibit a high
      adsorption activity for methyl blue, with the value of x ranging from 0 to 0.2,
      the adsorbance increases from 139.7 to 173.7 mg/g at the initial methyl blue
      concentration of 0.5 mg/mL in aqueous solution, and the kinetics data related to
      the adsorption of methyl blue onto the La1-xKxFeO3 microtubes are in good
      agreement with the pseudo-second-order kinetic model in the initial methyl blue
      concentration of 0.1-0.5 mg/mL.

PMID- 24734712
TI  - Catalytic upgrading of xylan over mesoporous Y catalyst.
AB  - In-situ catalytic cracking of xylan, a model compound of hemicellulose, was
      carried out using pyrolysis-gas chromatography/mass spectrometry over mesoporous
      Y for the first time. Experiments were conducted at three different temperatures,
      400 degrees C, 450 degrees C, and 500 degrees C, to investigate the effect of
      reaction temperature. Three different biomass-to-catalyst ratios, 1:1, 1:2, and
      1:3, were tested at 500 degrees C to examine the effect of catalyst dose. In
      addition, the catalytic activity of mesoporous Y was compared with that of Al-MCM
      41. The catalysts used were characterized by N2 adsorption-desorption,
      temperature programmed desorption of NH3, and X-ray diffraction. The main
      pyrolysis products of xylan were acids, hydrocarbons, phenolics, oxygenates,
      aromatics, and polycyclic aromatic hydrocarbons. Mesoporous Y, which has acid
      sites with larger quantity and stronger acidity than those of Al-MCM-41, was
      shown to enhance the quality of bio-oil to a larger extent, producing a larger
      quantity of high-value-added products, such as aromatics and furans.

PMID- 24734713
TI  - Molecular imprinting and immobilization of cellulase onto magnetic Fe3O4@SiO2
      nanoparticles.
AB  - Supermagnetic Fe3O4@SiO2 nanoparticles were molecular-imprinted prepared with
      cellulase as the template. The molecular imprinted nanoparticles were used as
      support to immobilization of cellulase. The transmission electron microscopy
      confirmed the core-shell structure and revealed that the size of the
      nanoparticles was around 10 nm. It was observed that cellulase was immobilized on
      the nanoparticles successfully from the Fourier transform infrared spectra. The
      adsorption of cellulase on the nanoparticles was specific and rapid. A high
      immobilization efficiency of 95% was achieved after the optimization. At 70
      degrees C, the half-life of the immobilized cellulase was 3.3-fold of the free
      enzyme. Compared with the free enzyme, the immobilized cellulase has the same
      optimal pH, higher optimal temperature, better thermal stability and higher
      catalytic efficiency. The results strongly suggest that the immobilized cellulase
      on molecular imprinted Fe3O4@SiO2 has the potential applications in the
      production of bioethanol, paper and pulp industry, and pharmaceutical industry.

PMID- 24734714
TI  - Effective removal of heavy metal ions using Mn2O3 doped polyaniline
      nanocomposite.
AB  - Mn2O3 doped Poly Aniline (MPANI) nanocomposite was prepared by chemical oxidative
      polymerization. Characterization of the MPANI nanocomposite was carried out using
      Fourier transfer infrared spectroscopy (FT-IR), Powder X-ray diffraction (XRD),
      Thermogravimetric analysis (TGA), Scanning electron microscopy (SEM) and Energy
      dispersive analysis of X-rays (EDAX). SEM image showed that the MPANI
      nanocomposite shows agglomerated sponge of 200-500 nm in length. XRD data
      revealed that the doping of Mn2O3 onto polymer surface which was confirmed due to
      the decrease in crystalline nature. The MPANI nanocomposite was used as an
      efficient adsorbent for removal Pb(II), Ni(II), and Cd(II) ions in aqueous media.
      Batch experiments show maximum adsorption capacity for MPANI nanocomposite on
      Pb(II) (437 mg/g), Ni(II) (494 mg/g), and Cd(II) (480 mg/g). The metal ions
      adsorption on MPANI nanocomposite is a fast process and the kinetics followed a
      pseudo second order rate equation (R2 approximately 0.99).

PMID- 24734715
TI  - Development and optimization of doxorubicin loaded poly(lactic-co-glycolic acid)
      nanobubbles for drug delivery into HeLa cells.
AB  - Microbubbles (MBs, usually 2-8 microm) as ultrasound contrast agent and drug
      carrier are promising for ultrasonic imaging and drug delivery. However, MBs
      posed some limitations due to their large diameters. In the current study, we
      developed a nanoscale bubbles (nanobubbles, NBs) by encapsulating the doxorubicin
      (DOX) into poly(lactic-co-glycolic acid) (PLGA) shells (denoted as DOX-PLGA NBs)
      for drug delivery into cancer cells. The size, morphology, particle stability,
      drug encapsulation efficiency, and drug payload were determined. The results
      showed that the DOX-PLGA NBs were uniform (270 +/- 3 nm) and spherical with a
      smooth surface, and were well dispersed and stable in water. The encapsulation
      efficiency and payload of DOX increased with its initial loading concentrations.
      The release behavior of DOX from the DOX-PLGA NBs exhibited a biphasic pattern
      characterized by an initial burst release followed by a slower and continuous
      release at both pH 7.4 and pH 4.4, and also presented in a pH-triggered releasing
      profile. The qualitative analysis of cellular internalization into HeLa cells by
      inverted fluorescence microscope showed that the cellular uptake of DOX-PLGA NBs
      was both concentration- and time-dependent. Moreover, the cell viability was also
      investigated using CCK-8 assay. It was found that DOX-PLGA NBs showed greater
      HeLa cell growth inhibition effect in vitro compared with free DOX. It was
      concluded that the DOX-PLGA NBs were biocompatible and appropriate for anti
      cancer drug delivery, and were potentially promising as a new therapeutic system
      for cancer treatment.

PMID- 24734716
TI  - Effect of growth temperature and quantum structure on InAs/GaAs quantum dot solar
      cell.
AB  - InGaAs-capped InAs quantum dots (QDs) and InAs QDs were adopted for the study of
      the effects through growth temperature and the band structure of InAs QDs on the
      performance of GaAs-based QD solar cell. It has been shown that the defects due
      to low temperature growth resulted in the decrease of Voc, Jsc and external
      quantum efficiency for GaAs bulk solar cell and QD embedded solar cells. It has
      been also found that InAs QDs act as defects by trapping photo-generated carries
      which affect the carrier transport in QD solar cell. The QD solar cell with
      InGaAs-capped InAs QDs showed higher performance than the QD solar cell with only
      InAs QDs. Such result has been explained by photo-generated carrier trapping and
      tunneling through InGaAs QW state in InGaAs-capped InAs QDs.

PMID- 24734717
TI  - Formation of two-dimensional ZnO nanosheets by rapid thermal oxidation in
      oxygenated environment.
AB  - Crystalline 2-D (dimensional) ZnO nanosheets were formed by rapid thermal
      oxidation of etched Zn foil in oxygen at 300 degrees C and 400 degrees C. Short
      oxidation time was varied from 10, 20 and 30 min. The morphologies and optical
      properties of the ZnO nanosheets evolved with the oxidation temperature and time.
      At 300 degrees C, ZnO nanosheets with thickness ranging from 32 nm to 80 nm were
      obtained while at 400 degrees C, the thickness of the nanosheets increased from
      88 nm to approximately 200 nm after 10 and 30 min of oxidation, respectively. The
      surface roughness of the ZnO nanosheets and grain size increased with oxidation
      time and temperature. Photoluminescence of the oxidized samples shows ultraviolet
      (UV) and visible emissions indicating good crystallinity of ZnO which was further
      confirmed by high-resolution transmission electron microscope observation of ZnO
      wurtzite interplanar spacing. Photocatalytic activity of ZnO was also
      investigated by using degradation of methyl orange (MO) and all the samples
      exhibit photocatalytic activity. The sample oxidized at 400 degrees C for 10 min
      show better MO degradation after 2 h of exposure due to higher surface area and
      better crystallinity of the ZnO nanosheets obtained.

PMID- 24734718
TI  - One dimensional spindle titanium oxide nanocrystals.
AB  - Anatase TiO2 nanocrystals of 10 nm were formed in aqueous solutions at 90 degrees
      C for 1 day. The solutions contained ammonium hexafluorotitanate (5 mM) and boric
      acid (15 mM). The nanocrystals connected each other to form particles of about
      100-500 nm. X-ray diffraction, Raman and FT-IR analysis revealed characteristics
      of the nanocrystals. They had BET surface area of 68 m2/g. Furthermore,
      morphology was controlled to one dimensional spindle shape by change of
      supersaturation degree. The spindle nanocrystals of 30 nm in width and 100 nm in
      length were formed in low concentration solutions. They contained
      hexafluorotitanate of 0.5 mM and boric acid of 0.15 mM. The spindle nanocrystals
      had higher crystallinity compared to the above nanocrystals. BET surface area
      reached 88 m2/g. One dimensional structure was realized by anisotropic crystal
      growth along c-axis. Low supersaturation degree decreased growth speed and
      brought out anisotropic crystal growth.

PMID- 24734719
TI  - Selective edge modification in graphene and graphite by chemical oxidation.
AB  - The effect of edge structures in graphene sheets has been well investigated
      theoretically but most experimental demonstrations of the functionalization have
      been for the bulk structures because of only a few reports on chemical methods to
      modify the edges selectively. We herein report a chemical method using the
      Lemieux-von Rudloff reagent that selectively oxidizes only the edges of graphene
      sheets. The selective oxidation at the edges of the graphene sheet was confirmed
      by thermogravimetric analysis (TGA), Raman mapping measurements, and X-ray
      photoelectron spectroscopy (XPS). The TGA result of the oxidized graphite with
      different particle sizes showed a slight weight loss at approximately 350 degrees
      C (2.29% for the middle particles (35 microm)), which indicates thermal
      decomposition of the oxidized edge part. The Raman mapping measurement in the
      inner part of graphene sheets didn't detect any defects or translational symmetry
      breaking after the oxidation. The XPS data clearly showed that the total carbon
      atom content present as C--O, C==O, and O--C==C increased from 4.65 to 6.18% by
      the oxidation. Using the obtained edge-oxidized graphene as a starting material,
      various functionalizations of the edge structure are expected in the future.

PMID- 24734720
TI  - Metal free growth of graphene on quartz substrate using chemical vapor deposition
      (CVD).
AB  - Graphene was grown on (0001) quartz substrate (z-cut) using catalyst free
      Chemical Vapor Deposition (CVD). Methane was used as a carbon source and hydrogen
      was introduced independently to optimize the growth. The effect of growth
      temperature was investigated while varying the temperature between 1000 and 1300
      degrees C. With an optimized condition, a thin (< or = 2 mono-layer) continuous
      graphene film was grown as confirmed by Raman spectroscopy, optical transmission,
      and electrical measurements. The best quality film showed the Raman D-peak to G
      peak intensity ratio of approximately 0.8 with the 2D-peak width of approximately
      60 cm(-1). High resolution X-ray Photoelectron Spectroscopy (XPS) revealed that
      the grown graphene is slightly oxidized but there is no detectable Si--C chemical
      bond in the graphene/quartz system. Hall effect measurements exhibited a carrier
      mobility of approximately 400 cm2/V x s with a sheet carrier density of
      approximately 5 x 10(12) cm(-2).

PMID- 24734721
TI  - Fabrication of GaAs/Al0.3Ga0.7As multiple quantum well nanostructures on (100) si
      substrate using a 1-nm InAs relief layer.
AB  - Nanometer scale thin InAs layer has been incorporated between Si (100) substrate
      and GaAs/Al0.3Ga0.7As multiple quantum well (MQW) nanostructure in order to
      reduce the defects generation during the growth of GaAs buffer layer on Si
      substrate. Observations based on atomic force microscopy (AFM) and transmission
      electron microscopy (TEM) suggest that initiation and propagation of defect at
      the Si/GaAs interface could be suppressed by incorporating thin (1 nm in
      thickness) InAs layer. Consequently, the microstructure and resulting optical
      properties improved as compared to the MQW structure formed directly on Si
      substrate without the InAs layer. It was also observed that there exists some
      limit to the desirable thickness of the InAs layer since the MQW structure having
      thicker InAs layer (4 nm-thick) showed deteriorated properties.

PMID- 24734722
TI  - Application of mesoporous Al-MCM-48 material to the conversion of lignin.
AB  - Al-MCM-48 was applied to the catalytic pyrolysis of lignin for the first time.
      The pyrolysis reaction and in-situ product were analyzed by pyrolysis gas
      chromatography/mass spectrometry. The main products of the non-catalytic
      pyrolysis of lignin were phenols. The use of Al-MCM-48 increased the production
      of light phenols considerably. The yields of high-value-added compounds, such as
      hydrocarbons and aromatics, were also increased by catalytic upgrading. Al-MCM-48
      is believed to promote cracking, aromatization and deoxygenation, such as
      decarbonylation. On the other hand, Si-MCM-48, which has no acid sites, showed
      lower deoxygenation efficiency than Al-MCM-48. Al-MCM-48 could be regenerated by
      calcining in air.

PMID- 24734723
TI  - Cooperative rotation of alkylated sulfide molecules at the liquid-graphite
      interface.
AB  - Self-assembled monolayers of hexadecyl sulfide adsorbed on a graphite surface
      were studied using scanning tunneling microscopy (STM). STM images of the
      molecule indicate a bright spot and two relatively dim thin bands that correspond
      to the sulfur atom positioned at the center of the molecule and two alkyl chains
      that extend linearly from the sulfur atom, respectively. The contrast of the
      bands changes reversibly between the zigzag and aligned bright spots, which
      correspond to the zigzag methylene units of the alkyl chains; accordingly, the
      methylene units alternate between parallel and perpendicular orientations to the
      surface, respectively, on a time scale of minutes. The variation in contrast
      indicates cooperative rotation along the long axis of the molecules in the
      monolayer at the liquid-graphite interface. The reversibility of the contrast
      suggests that the solvent influences the difference in the free energies of the
      parallel and perpendicular configurations of the molecules with respect to the
      graphite surface.

PMID- 24734724
TI  - Incorporation of graphene oxide in quantum dot sensitized photocatalyst based on
      ZnO nanorods.
AB  - The novel efficient architecture of photocatalyst is fabricated by incorporating
      graphene oxide (GO) in quantum dots (QDs) sensitized ZnO nanorods and the
      photocatalytic properties for methyl orange (MO) degradation are investigated by
      scanning electron microscopy (SEM), transmission electron microscopy (TEM), X-ray
      diffraction (XRD), UV-vis-NIR absorption spectroscopy. The results indicate that
      the incorporating of grapheme oxide is more favourable for the degradation. The
      improved photocatalytic properties can take several advantages given that the
      higher carrier mobility of GO which can reduce the recombination of carriers, and
      assembled quantum dots which can facilitate the absorption of solar light. The
      paper provides the clue to design the effective and easy recyclable
      photocatalyst.

PMID- 24734725
TI  - Hard coating for polymer substrates through lamination and peeling of porous
      anodized zirconia.
AB  - Transparent and hard zirconia (ZrO2) films with thicknesses in the range of 1.5
      to 1.8 microm were successfully formed on various polymer surfaces, i.e.,
      polycarbonate (PC), polystyrene (PS), polyethylene terephthalate (PET) and
      polymethylmethacrylate (PMMA) with excellent adhesion and without cracking, while
      preserving their bulk properties. Our process is based on a lamination of porous
      anodized ZrO2 membranes (PAZMs) to the polymer surfaces through capillary action,
      followed by simple peeling with tweezers to remove the unanodized metal Zr foil.
      The resulting PAZM-laminated surfaces exhibited excellent surface chemical and
      physical durability. Our technique also allowed the reuse of a single Zr foil
      piece multiple times for several anodization and lamination cycles.

PMID- 24734726
TI  - Synthesis of Ag nanoparticles with tunable sizes using N,N-dimethyl formamide.
AB  - Ag nanoparticles (NPs) were fabricated using N,N-Dimethyl formamide (DMF) as a
      solvent and reducing agent together with polyvinyl pyrrolidone (PVP) through a
      solvothermal method. The position of surface plasmon resonance (SPR) band of as
      prepared Ag NPs changed with the chain length of PVP and red shifted with
      increasing the molecular weight of PVP. The concentration of PVP and reaction
      time affected the position of absorption peaks. The selective adsorption of PVP
      on the {100} and {111} facets of Ag depended on the kinds of solvents, which
      determined the driving force of the growth process of nanostructures. For
      comparison, ethylene glycol, water, and ethanol was added serving as solvents in
      the presence of PVP. The result indicates that DMF is a vital factor to
      kinetically control the formation of Ag NPs. Therefore the favorable facets of Ag
      nanostructures are {111} facets in a DMF solution. Ag nanoplates together with
      nanowires were observed in the system of ethanol and water, respectively.

PMID- 24734727
TI  - Extraordinary mid-infrared transmission of subwavelength holes in gold films.
AB  - Gold (Au) nanoholes are fabricated with electron-beam lithography and used for
      the investigation of extraordinary transmission in mid-infrared regime.
      Transmission properties of the nanoholes are studied as the dependence on hole
      size. Transmittance spectra are characterized by Fourier transform infrared
      spectroscopy (FTIR) and enhanced transmittance through the subwavelength holes is
      observed. The transmission spectra exhibit well-defined maximum and minimum of
      which the position are determined by the lattice of the hole array. The hole-size
      primarily influence the transmission intensity and bandwidth of the resonance
      peak. With an increase of hole-size, while keep lattice constant fixed, the
      intensity of the resonance peak and the bandwidth increases, which are due to the
      localized surface plasmons. Numerical simulation for the transmission through the
      subwavelength holes is performed and the simulated results agree with the
      experimental observations.

PMID- 24734728
TI  - Fabrication of bi-layer graphene and theoretical simulation for its possible
      application in thin film solar cell.
AB  - High quality graphene film is fabricated using mechanical exfoliation of highly
      oriented pyrolytic graphite. The graphene films on glass substrates are
      characterized using field-emission scanning electron microscopy, atomic force
      microscopy, Raman spectroscopy, UV-vis spectroscopy and Fourier transform
      infrared spectroscopy. A very high intensity ratio of 2D to G-band (to
      approximately 1.67) and narrow 2D-band full-width at half maximum (to
      approximately 40 cm(-1)) correspond to the bi-layer graphene formation. The bi
      layer graphene/p-GaN/n-InGaN/n-GaN/GaN/sAl2O3 system is studied theoretically
      using TCAD Silvaco software, in which the properties of exfoliated bi-layer
      graphene are used as transparent and conductive film, and the device exhibits an
      efficiency of 15.24% compared to 13.63% for ITO/p-GaN/n-InGaN/n-GaN/GaN/Al2O3
      system.

PMID- 24734729
TI  - Dispersion of boron nitride nanotubes in aqueous solution by simple aromatic
      molecules.
AB  - We report that the simple aromatic molecules successfully disentangle and
      disperse multi-walled boron nitride nanotubes (BNNTs) in aqueous solutions
      through pi-pi stacking interactions. Aromatic molecules such as derivatives of
      naphthalene, anthracene, and pyrene were used as dispersants and components for
      construction of nanohybrids. Spectroscopic analyses of water-dispersed BNNTs
      revealed that not only numbers of aromatic rings but also substituted functional
      groups were essential for dispersion capabilities. It was suggested that greater
      numbers of aromatic rings and a carboxylic acid as the substituted group showed
      higher dispersion capabilities among the molecules used in this study. Detailed
      microscopic analyses using atomic force microscopy and transmission electron
      microscopy showed certain isolation capabilities of the aromatic molecules for
      BNNTs in aqueous solution. Moreover, fluorescence spectra indicated that BNNTs
      and the aromatic molecules have different electronic states after hybrid
      formation. Our results using the simple aromatic molecules will be utilized as a
      basic data for dispersion of BNNTs and construction of disentangled BNNT
      nanohybrids effectively.

PMID- 24734730
TI  - Porous tubular rutile TiO2 nanofibers: synthesis, characterization and
      photocatalytic properties.
AB  - Electrospinning was employed to synthesize tubular TiO2 nanofibers. The as-spun
      fibers were subjected to heat treatment at 800 degrees C for 1 h in the air. By
      controlling the polymer concentration, pores measuring 30-60 nm were formed on
      the side walls of the tubular nanofibers. During annealing, the average nanofiber
      diameter shrank from 150 nm to 120 nm. The structural properties were
      characterized by XRD, Raman and FTIR spectroscopy. Further porous and tubular
      structures were confirmed by SEM and HRTEM. The specific surface area of porous
      tubular nanofibers (PTNFs) was measured using the Brunauer-Emmett-Teller (BET)
      method, which revealed a high surface area of 63 m2 g(-1). Photodegradation of
      methyl orange demonstrated that the PTNFs have higher photocatalytic activity
      than nonporous nanofibers. This enhanced photocatalytic activity can be
      attributed to the high surface area of the porous and tubular structures.

PMID- 24734731
TI  - Synthesis and properties of cathode materials xLi2MnO3 x (1-x)LiMn1/3Ni1/3Co1/3O2
      for Li-ion batteries.
AB  - Lithium- and manganese-rich layered electrode materials, represented by the
      general formula xLi2MnO3 x (1-x)LiMO2 in which M is Mn, Ni, and Co, are of
      interest for both high-power and high-capacity lithium ion batteries. In this
      paper, a series of nano-sized materials based on the xLi2MnO3 x (1
      x)LiMn1/3Ni1/3Co1/3O2 (x = 0, 0.2, 0.4, 0.6) as a cathode material for lithium
      batteries were synthesized by the sol-gel method, citric acid as a chelating
      agent. Its structural and electrochemical properties were investigated using X
      ray diffractometry, scanning electron microscopy, galvanostatic charge-discharge
      test. Differences between electrochemical and chemical activation of the Li2MnO3
      component are discussed. The results indicated that well-ordering layered
      xLi2MnO3 x (1-x)LiMn1/3Ni1/3Co1/3O2 (x = 0, 0.2, 0.4, 0.6) cathode materials were
      successfully prepared with alpha-NaFeO2 typical crystal. It is found that the
      changes in compositional, crystal structure and electrochemical performance
      depend highly on the different values of x. The charge-discharge capacity and
      cycle number plots confirm unequivocally that the Li2MnO3 component serves to
      stabilize LiMn1/3Ni1/3Co1/3O2 electrodes to electrochemical cycling. The study
      emphasizes that, for high values of x, a relatively small LiMn1/3Ni1/3Co1/3O2
      concentration stabilizes a layered Li2MnO3 electrode to reversible lithium
      insertion and extraction. The composition x = 0.2 leads to the best
      electrochemical performance cathode material with high capacity of 253 mA h/g and
      high-rate property.

PMID- 24734732
TI  - Surface-enhanced Raman spectroscopy-active substrates: adapting the shape of
      plasmonic nanoparticles for different biological applications.
AB  - We discuss the relationship between the shape of plasmonic nanoparticles and the
      biological surface-enhanced Raman spectroscopy (SERS) applications which they can
      enable. As a step forward in developing SERS-active substrates adapted to a
      particular application, we demonstrate that a modification of the widely used
      protocol for the sodium citrate mediated reduction of chloroauric acid, which is
      typically employed only for obtaining spherical gold nanoparticles, can yield
      flat polygonal nanoparticles at room temperature and a decreased amount of the
      reducing agent. The significant advantage of the described approach is that it
      allows for synthesis of nanoparticles with different geometries using a well
      established synthesis protocol without the need for any additional chemicals or
      special synthesis apparatus. By contrasting spherical and anisotropically shaped
      nanoparticles, we demonstrate that multifaceted nanoparticles with sharp edges
      are better suitable for SERS analysis of low concentration analytes requiring
      strong SERS enhancement. On the other hand, gold nanoparticles with isotropic
      shapes, while giving a smaller enhancement, can provide a more reproducible SERS
      signal. This is important for analytical applications of complex biological
      systems where large SERS enhancement may not always be required, whereas data
      reproducibility and minimal false positive rate are imperative. Using a SERS
      active substrate comprising isotropically shaped gold nanoparticles, we
      demonstrate the differences between Gram-negative (E. coli) and Gram-positive (S.
      aureus) bacteria, attributable to the outer membrane and peptidoglycan layer,
      with the level of detail which has not been previously reported with optical
      spectroscopic techniques.

PMID- 24734733
TI  - Synthesis and optical properties of Eu3+ doped ZnO nanoparticles used for white
      light emitting diodes.
AB  - ZnO nanoparticles doped with trivalent europium ions (Eu3+) were synthesized by
      the hydrothermal method. The structural properties of the samples were
      investigated by the X-ray diffraction (XRD). The results indicated that Eu3+ was
      incorporated into the lattice of ZnO. Photoluminescence (PL) measurements of
      ZnO:Eu3+ showed a strong red luminescence emission. Specially, the red emission
      can be obtained even under the nonresonant excitation of 320 nm, and it is
      explained by an energy transfer mechanism in which the energy is transferred from
      ZnO matrix to Eu3+. These results indicate that the ZnO:Eu3+ is the attractive
      candidate phosphor for the application in phosphor-converted light-emitting
      diodes (pc-LEDs) as red phosphor. The intensity of Eu3+ PL decreased with the
      increasing Eu3+ concentration and the concentration quenching mechanism was
      presented based on non-radiative recombination processes in ZnO and the energy
      back-transfer from the excited state of Eu3+ to the ZnO host. Moreover, the
      samples were synthesized under low temperature condition.

PMID- 24734734
TI  - Long term synthesis of needle crystal assembled TiO2 films in an aqueous
      solution.
AB  - Crystals of TiO2 grew on substrates in aqueous solutions at 50 degrees C for 180
      day. Long term synthesis brought us nano-structured films and information of
      crystal growth. The films showed 101 diffraction peak of anatase phase.
      Morphology of the crystals well developed to needle shapes. They stood
      perpendicular to the substrates. The films had nano-structured surfaces. Surface
      nanostructures would contribute to high sensitive sensors, solar cells,
      photocatalysis, etc. The films had high transparency compared to bare substrates
      in the range 360-525 nm.

PMID- 24734735
TI  - Fabrication of Al-beta/silicalite-1 hydrophilic-hydrophobic zeolite membranes.
AB  - Hydrophobic-hydrophilic composite membranes containing silicalite-1 and Al-beta
      zeolites are prepared on the outer surface of the porous alpha-alumina tube for
      the first time. The hydrophilic layer with aluminum serves as an active catalytic
      domain, whereas the hydrophobic layer containing silicalite-1 with medium pore
      size is expected to assist in separating the reaction products based on their
      hydrophobicity as well as shape-selectivity. The continuous defect-free composite
      membranes are fabricated by two-step synthesis approach by initial deposition of
      Al-beta crystals on the outer surface of porous alumina tube followed by coating
      of silicalite-1 crystals over the Al-beta layer in the second step under
      hydrothermal conditions. The composite membranes exhibited a high thermal
      stability of up to 550 degrees C. The powder X-ray diffraction patterns of
      samples collected at the bottom of crystallization vessel as well as coated
      membranes indicated typical BEA and MFI structures consisting of ca. 0.5-0.7 nm
      size micropores, and free from impurity phase. The field emission scanning
      electron microscopic (FE SEM) analysis of the silicalite-1 sample exhibited
      uniform rectangular crystals of size about 20 microm; whereas Al-beta showed
      spherical morphology with crystal size of approximately 0.6-0.7 microm. The
      surface and cross-sectional analyses of composite membranes both before and after
      calcinations exhibited defect-free microstructures for the composite membranes.
      The calcined membranes exhibited single gas permeation and the observed values
      for composite membranes are an order of magnitude lower than that of the
      individual membranes.

PMID- 24734736
TI  - Preparation of magnetic Fe3O4@SiO2 nanoparticles for immobilization of lipase.
AB  - Magnetic Fe3O4 nanoparticles were prepared with coprecipitatation method and
      covered with SiO2 to form the core-shell Fe3O4@SiO2 nanoparticles. Then the
      nanoparticles were modified with glutaradehyde for functionalization of the
      surface to aldehyde groups. The transmission electron microscopy confirmed the
      core-shell structure and revealed that the size of the nanoparticles was around
      10 nm. It was observed that the lipase was immobilized on the nanoparticles
      successfully from the Fourier transform infrared spectra. The immobilized lipase
      on Fe3O4@SiO2 nanoparticles was characterized and compared to free enzyme. There
      are no significant differences observed in the optimal pH, temperature and Km
      before and after immobilization. However, the immobilized lipase displayed higher
      relative activity in the range of pH from 7.0 to 9.5. Compare with the free
      enzyme, the immobilized one showed higher thermal stability at temperature range
      from 30 to 70 degrees C, especially at high temperature. The relative activity of
      immobilized enzyme was 5.8 fold of the free lipase at 70 degrees C after 10 h
      incubation. Thus, the prepared lipase was proved to have the advantages like
      higher relative activity, better stability, broader pH range and easy to
      recovery. These results suggest that immobilization of lipase on Fe3O4@SiO2
      nanoparticles has the potential industrial applications.

PMID- 24734737
TI  - Construction of late transition metal complex on amine-functionalized SiO2 and
      SBA-15 for L-lactide polymerization.
AB  - We report the in-situ synthesis of a late transition metal catalyst on amine
      functionalized SBA-15 and amorphous silica and their ring opening polymerizations
      of L-lactide. Funtionalizations of SBA-15 and amorphous silica with N-[3
      (trimethoxysilyl)propyl]-ethylenediamine (2NS) were carried out to in-situ
      synthesize late transition metal catalysts on the surface of nanoporous
      materials. FT-IR spectra indicates that the 1,2-dimethoxyethane ligand did not
      participate in the reaction when (DME)NiBr2 was immobilized on the amine
      functionalized silica. In addition, the XPS spectrum confirmed the presence of Ni
      compound on the 2NS-functionalized SiO2. SBA-15/2NS/Ni and SBA-15/ 2NS/Pd
      catalysts showed higher conversion of PLA polymerization in comparison to
      SiO2/2NS/Ni and SiO2/2NS/Pd, respectively. The molecular weights of PLA produced
      by SBA-15/2NS/Ni or Pd were larger than those of SiO2/2NS/Ni or Pd, respectively.
      The effects of polymerization conditions such as the polymerization temperature,
      time, the catalyst amount in the feed, and the polymerization medium in L-lactide
      polymerization were also investigated.

PMID- 24734738
TI  - Chemical force microscopy using functionalized ZnO whisker probe tips.
AB  - We have developed an atomic force microscope-based technique utilizing a zinc
      oxide whisker crystal as a probe tip. This technique was used for measuring
      interactions between the chemically modified tip and oxidized silicon substrates
      as a function of solution pH. Surfaces terminating in amine and methyl functional
      groups were prepared by covalently modifying the silicon substrate with self
      assembled monolayers of (3-amino-propyl)triethoxysilane and n
      butyltrichlorosilane, respectively. Patterned samples prepared by microcontact
      printing consisted of amine-terminated square regions surrounded by a methyl
      terminated background. The contrast in lateral force images of the patterned
      samples obtained with amine-functionalized tips was seen to strongly depend on
      solution pH. High friction was observed between the attractive and strongly
      interacting functional groups in the methyl-terminated regions at low pH values
      and the amine-terminated regions at intermediate pH values. Low friction was
      observed between repulsive and weakly interacting functional groups. In addition,
      interacting force measurements on approach showed long-range attractive forces
      between the amine-terminated surfaces at intermediate pH values. Adhesive force
      measurements showed a dependency on the state of ionization of the amine groups,
      which was controlled by varying the pH. The pKa value estimated from the
      measurements was shifted to a lower pH than that of primary amine groups in
      solution. These results show that functionalized ZnO whisker probe tips have
      great potential for chemically sensitive imaging.

PMID- 24734739
TI  - Synthesis of polyaniline-coated carbon nanotubes and study on their pH-sensitive
      conductivity.
AB  - We report the synthesis of polyaniline-coated-carbon nanotubes (PANI-c-CNTs)
      composites by using water-soluble CNTs with phenyl sulfonate groups as templates.
      A series of characterizations including transmission electron microscopy (TEM),
      Fourier-Transform Infrared Spectroscopy (FTIR) and UV-vis spectroscopy were
      conducted to investigate the formation of PANI coating on the surfaces of the
      CNTs. The thickness of PANI coating in the PANI-c-CNTs composites was controlled
      by adjusting concentrations of aniline and CNTs. The conductivities of PANI-c
      CNTs composites were measured by using conductive atomic force microscopy (c
      AFM). It was found that the conductivities of PANI-c-CNTs composites were
      remarkably affected after doping and dedoping process of PANI coating by
      different pH solution. Therefore, our preliminary result indicates that as
      prepared PANI-c-CNTs composites may be used as gas sensor such as HCl and NH3
      vapor.

PMID- 24734740
TI  - Synthesis of highly crystalline titania nanocrystals through solvothermal
      technique.
AB  - Highly crystalline rhombic TiO2 nanocrystals (NCs) were fabricated through a
      solvothermal technique in anhydrous ethanol. A Teflon cup with reaction agents
      including titanium (IV) isopropoxide, oleic acid (OA), oleylamine (OM), and
      anhydrous ethanol was put into a Teflon-lined stainless steel autoclave with
      ethanol and water for the purpose of controlling the hydrolytic reaction of Ti
      precursors. Water vapor generated from the mixture of water and ethanol was as a
      hydrolysis agent and oleic acid and oleylamine were as two distinct capping
      surfactants which have different binding strengths to control the growth of the
      TiO2 NCs. The molar ratios of oleic acid/oleylamine play a crucial role for the
      size and morphology of TiO2 NCs created through hydrolytic and nonhydrolytic
      processes. Highly crystalline rhombic TiO2 NCs were fabricated by combining
      hydrolytic and nonhydrolytic sol-gel reactions of titanium (IV) isopropoxide
      using a molar ratio of Ti precursors/OA/OM of 1/2/3 at 180 degrees C for 22 h.
      The transmission electron microscopic observations indicated that the rhombic
      TiO2 NCs have a uniform size distribution under optimal preparation conditions.
      The size and size distribution of the rhombic TiO2 NCs were adjusted by adding OM
      to the reaction mixture as a cosurfactant together with OA.

PMID- 24734741
TI  - Poly(lactic acid) microparticles coated with insulin-containing layer-by-layer
      films and their pH-dependent insulin release.
AB  - Poly(lactic acid) (PLA) microparticles were coated with layer-by-layer (LbL)
      films containing insulin and the pH-dependent release of insulin was studied. The
      LbL films were prepared on the surface of PLA microparticles by the alternate
      deposition of insulin and poly(allylamine hydrochloride) (PAH) through the
      electrostatic attraction between insulin and PAH. The insulin loading on the PLA
      microparticles depended on the film thickness, which corresponded to the number
      of insulin layers, and on the pH of the solution used to deposit insulin. The
      insulin loading increased with the film thickness and when the film was prepared
      at pH 7.4. The LbL films decomposed upon exposure to acidic solutions because the
      electrostatic attraction between the insulin and the PAH in the films disappeared
      when the charge on insulin changed from negative to positive at an acidic pH,
      which resulted in the release of insulin. The temperature and salt concentration
      did not affect the pH stability of the LbL films. The pH threshold for insulin
      release was pH 5.0-6.0, which corresponds to isoelectric point of insulin, 5.4.
      The release of insulin from the microparticles was rapid, and was almost complete
      within a few minutes. The circular dichroism spectra showed that the released
      insulin retained its original secondary structure. Our insulin-loaded PLA
      microparticles may be useful for the controlled release of insulin.

PMID- 24734742
TI  - Difference in protein adsorption onto polymer films with or without thermal
      annealing.
AB  - Protein adsorptions onto non-annealed (NA) and thermally annealed (TA)
      polyetherimide films were examined by surface plasmon resonance measurements.
      Proteins adsorbed onto the NA films with smaller adsorption constants in
      comparison with the TA films. Neutron reflectivity measurements of the two films
      suggested that the outermost region of the NA films swelled with larger amounts
      of water molecules than the TA films. It is plausible that the aforementioned
      difference in the protein adsorption properties is derived from the difference in
      the interfacial aggregation structures of the two films.

PMID- 24734743
TI  - Hydroisomerization of n-dodecane over Pt/Al-MCM-48 catalysts.
AB  - The objective of this study is to evaluate the catalytic potential of Pt/Al-MCM
      48 catalysts in hydroisomerization of n-dodecane. The effects of the Si/Al ratio
      and platinum loading on the acid characteristics of Al-MCM-48 and the catalytic
      performance in n-dodecane hydroisomerization were analyzed. The catalysts were
      characterized by X-ray diffraction, nitrogen adsorption, infrared spectroscopy of
      pyridine adsorption, and temperature programmed desorption of ammonia. The number
      of weak strength acid sites on Al-MCM-48 increased with 0.5 wt% platinum loading.
      The weak strength acid sites of Pt/Al-MCM-48 catalysts were ascribed to Lewis
      acid sites, which can be confirmed by NH3-TPD and FTIR spectra of pyridine
      adsorption. Iso-dodecane can be produced with high selectivity in n-dodecane
      hydrosisomerization over Pt/Al-MCM-48 catalysts. This is attributed to the mild
      acidic properties of Pt/Al-MCM-48 catalysts.

PMID- 24734744
TI  - Electrical and optical characterization of copper oxide/calcium oxide
      nanocomposite fibers.
AB  - The Poly(vinyl alcohol)/copper acetate/calcium acetate sol was prepared by sol
      gel route. Poly(vinyl alcohol)/copper acetate/calcium acetate composite
      nanofibers were synthesized by electrospinning process. These nanofibers had an
      average diameter of 200 nm. Calcining these fibers at 1000 degrees C produced
      copper oxide/calcium oxide nanofibers with average diameter of 75 nm. These
      fibers were characterized by Atomic Force Microscopy, Scanning Electron
      Microscopy, Fourier Transform Infrared spectroscopy, powder X-ray Diffraction,
      Ultraviolet spectroscopy, dielectric study and Second Harmonic Generation (SHG)
      efficiency test. Band gap energy was calculated as 4.1 eV. SHG efficiency was
      found to be 1.7 times than that of KDP.

PMID- 24734745
TI  - Dispersion of nano-sized hydrophilic silica particles into various hydrophobic
      polymer networks.
AB  - Dispersion of fine silica particles with hydrophilic surfaces to the hydrophobic
      polymer network has been investigated. Strength-controlled agglomerates of silica
      particles with 190 nm diameter were prepared, and they were blended with some
      polymers in an intensive mixer. Through the shear breakdown of the silica
      agglomerates in the kneaded polymer melts, the isolated primary silica
      nanoparticles with hydrophilic surfaces were dispersed uniformly into
      polycarbonate, as well as poly(ethylene-ran-vinylalcohol), polystyrene, and
      poly(tetrafluoroethylene-co-perfluoropropylvinylether) selected as a matrix
      polymer in the authors' previous studies. Unexpected result was the well
      dispersion of the hydrophilic silica particles into hydrophobic polymers. Taking
      the extremely hydrophobic perfluoropolymer as an example, the reason why silica
      particles can disperse into a hydrophobic polymer was also discussed by comparing
      the quite short-range (< or = 0.4 nm) attractive interaction energies between
      silica nanoparticle and polymer melt with that between silica nanoparticles
      calculated on the assumption that the agglomerate is peeling off at the shear
      breakdown stage. The main finding of this study is that the attractive silica
      perfluoropolymer interaction may exceed the silica-silica interaction under the
      special condition where the perfluoropolymer chains wind about the silica
      surfaces in nano-areas (less than 1% of the whole surface area of the silica
      particle), resulting in the well dispersion of nano-silica into the
      perfluoropolymer.

PMID- 24734746
TI  - Vapour phase hydrogenolysis of glycerol over nano Ru/SBA-15 catalysts on the
      effect of preparatory routes and metal precursors.
AB  - The effect of preparation method and metal precursor of ruthenium employed during
      the preparation of Ru/SBA-15 catalysts were investigated. The catalytic
      functionalities are evaluated during the vapour phase hydrogenolysis of glycerol
      to 1,2-propyleneglycol, 1,3-propylene glycol and ethylene glycol. The catalysts
      exhibit high conversion/selectivity for 3 wt%Ru (3Ru/SBA-15) catalysts during
      glycerol hydrogenolysis. CO-chemisorption results suggest that the variation in
      the dispersion of Ru on SBA-15 support. These catalysts were characterized by
      XRD, TPR, TEM, BET surface area, pore size distribution and CO-chemisorption
      measurements. The Ru/SBA-15 catalysts synthesized from micro-emulsion method and
      polyol method have shown higher catalytic activity than the samples prepared by
      impregnation method and deposition-precipitation method. The catalytic behavior
      during glycerol hydrogenolysis is attributed to the formation of nano particles
      of ruthenium.

PMID- 24734747
TI  - Synthesis of near-infrared-emitting CdTe/CdSe/ZnSe/ZnS heterostructure.
AB  - Near-infrared-emitting quantum dots (QDs) were fabricated via organic synthesis
      strategies through constructing CdTe/CdSe/ZnSe/ZnS multishell heterostructure. An
      effective shell-coating route was developed for multishell growth on CdTe cores.
      Core/shell growth was monitored by absorption and photoluminescence (PL)
      spectroscopy and transmission electron microscopy observation. Yellow emitting
      CdTe cores were coated with a CdSe shell to generate type II structure. This
      yields core/shell QDs with red photoluminescence. The passivation by the ZnSe
      shell having a substantially wide bandgap confines the excitons within the
      CdTe/CdSe interface and isolates them from the solution environment and
      consequently improves the stability of the heterostructure. An additional ZnS
      shell was deposited around the outer layer of CdTe/CdSe/ZnSe QDs to form a
      heterostructure through the reaction between zinc oleate and trioctylphosphine
      sulfur in the crude CdTe/CdSe/ZnSe solution. By varying CdTe core size and each
      shell thickness, the PL wavelength of the obtained heterostructure can span from
      580 to 770 nm. The PL efficiency is quenched in CdTe QDs in diluted solution but
      increases substantially up to 24% for CdTe/CdSe core/shell QDs. The PL efficiency
      of CdTe/CdSe/ZnSe/ZnS QDs with average diameter of 5.4 nm and a PL peak
      wavelength of 770 nm is 20%.

PMID- 24734748
TI  - Application of functionalized nanoparticle for mass spectrometry.
AB  - We synthesized functionalized nanoparticles (NPs) by in mixing aqueous solutions
      of 3d transition metal (iron, or manganese) chlorides (MCl2 x nH2O) and (3
      aminopropyl)triethoxysilane, and in this unique method, monodispersed NPs were
      obtained in a single step. The prepared NPs examined by X-ray diffraction,
      transmission electron microscope, Fourier transform infrared spectroscopy and
      zeta potential measurement. The synthesized NPs surround by amorphous SiO2 and
      possess amino and hydroxyl groups on NPs surface. The number-average diameter of
      the NPs was determined to be about 3 and 5 nm. The NPs worked as an ionization
      assisting reagent in mass spectrometry (MS) by means of what is called
      nanoparticle assisted laser desorption/ionization (nano-PALDI) MS has begun to be
      used to analyze low molecular compound. In this paper, we introduced analysis of
      the food product and pesticide as environmental pollutant by using nano-PALDI MS.

PMID- 24734749
TI  - Adsorption characterization of gaseous volatile organic compound on mesoporous
      silica particles prepared from spent diatomaceous earth.
AB  - This study used spent diatomaceous earth (SDE) from drink processing as source of
      Si and cationic surfactant (CTAB) as a template for the synthesis of mesoporous
      silica Materials (MSM) through hydrothermal method. The MSM was characterized by
      Small-angle X-ray Diffraction (SXRD), Scanning Electron Microscopy (SEM), Thermo
      Gravimetric Analysis (TGA), Fourier Transform Infrared (FT-IR) spectroscopy and
      N2 adsorption-desorption analyzer. The results showed that the surface area, pore
      volume and pore size was roughly ranged from 880 to 1060 m2 g(-1), 1.05 cm3 g(-1)
      and 4.0 nm, respectively. The properties of the synthesized MSM were also
      compared with those prepared from pure silica sources (MCM-41) and got almost the
      same characteristics. The synthesized MSM was used as adsorbent at 25 degrees C
      with carrier gas of air. The adsorption equilibrium revealed that adsorption
      capacity of MSM was 59.6, 65.7, 69.6, 84.9 mg g(-1) while the acetone
      concentration was 600, 800, 1000 ppm, 1600 ppm respectively. Results showed that
      breakthrough curves correlate to the challenge vapor concentration, adsorbent
      loading, and the flow rate. The results obtained in the present work demonstrated
      that it was feasibility of using the SDE as a potential source of silica to
      prepare MSM.

PMID- 24734750
TI  - Liquid-phase hydrogenation of phenylacetylene over the nano-sized Pd/TiO2
      catalysts.
AB  - Understanding the mechanisms of metal-support interaction and/or adhesion and
      growth of the metal particles is important not only in the field of catalysis but
      also the design of advanced nanostructure materials. In the present work, the
      strong metal-support interaction (SMSI) effect occurred on the Pd/TiO2 catalysts
      synthesized by the sonochemical method when reduced at 500 degrees C whereas the
      ones prepared by the conventional impregnation resulted in sintering of Pd0
      particles instead. The presence of SMSI was correlated to the amount of oxygen
      vacancies or Ti3+ defective sites. Smaller Pd0 particles with more uniform size
      distribution on the sonochemical-derived catalysts may promote hydrogen spillover
      from Pd0 surface to TiO2 support so that the reduction of Ti4+ to Ti3+ occurred,
      resulting in the SMSI. As a consequence, the catalysts exhibited improved
      catalytic performances in the liquid-phase selective hydrogenation of
      phenylacetylene to styrene.

PMID- 24734751
TI  - The structure of graphene/nickel interfaces within nickel-encapsulating carbon
      nanocapsules studied by high-resolution transmission electron microscopy.
AB  - Nickel (Ni)-encapsulating carbon nanocapsules (CNCs) were synthesized by vacuum
      deposition. The graphene/Ni interfaces within the CNCs were observed by high
      resolution transmission electron microscopy. From lattice imaging, the
      orientational relationship and atomic configuration at the interfaces were
      investigated. It was found that the interlayer spacing at the
      (0001)graphene/(001)Ni interfaces was 0.21 +/- 0.05 nm. The interfaces within
      Ni3C-encapsulating CNCs, synthesized by the same method, were also examined.

PMID- 24734752
TI  - Fabrication of visible-light-driven N-doped ordered mesoporous TiO2
      photocatalysts and their photocatalytic applications.
AB  - Herein we report a facile method for the synthesis of N-doped crystalline
      mesoporous titanium dioxide (NMT) with ordered structure. Structural
      characterization and HR-TEM studies revealed that NMT exhibits pure anatase phase
      with highly crystalline ordered mesoporous structure in NMT. The N2 isotherms are
      of type IV with an H1 hysteresis loop and a pronounced capillary condensation
      step at high relative pressure for NMT, suggesting the presence of well-ordered
      mesoporous structure. The reflectance spectrum of NMT shows stronger absorption
      in the visible region above 400 nm, owing to the substitution of the lattice
      oxygen by nitrogen. XPS results proved the doping of nitrogen in to oxygen in
      TiO2 lattice, which confirmed by the presence of peak at 401 eV for N1s. The
      efficiency of photocatalyst was evaluated by the degradation of Rhodamine-B and
      antibacterial activity against E. coli under visible-light irradiation. N-doped
      mesoporous TiO2 shows superior photocatalytic and anti-bacterial activity
      compared to pure TiO2 under visible-light irradiation. The enhanced
      photocatalytic activity of NMT is attributed to synergistic effect of NMT that is
      N-doping and well ordered crystalline mesoporous structure with high surface area
      of NMT. These findings suggest that N-doped mesoporous TiO2 has potential
      application in many areas such as degradation of hazardous pollutants, anti
      bacterial agents, fuel cells, battery electrode, sensors, opto electronic
      devices, photo active self-cleaning surfaces.

PMID- 24734753
TI  - Vapour phase oxidation of toluene over CeAlPO-5 molecular sieves.
AB  - Single-site CeAlPO-5 with Al/Ce ratios 25, 50, 75, 100 and 125 were synthesized
      hydrothermally in fluoride medium. The XRD patterns of CeAlPO-5 exhibited
      characteristic reflections of AlPO-5. 27Al MAS-NMR of CeAIPO-5(25) showed two
      unusual peaks at -20.78 and -71.35 ppm due to delocalization of cerium unpaired
      electron. However, 31P MAS-NMR exhibited the usual characteristic peak similar to
      that of AlPO-5. Vapour phase oxidation of toluene in air over CeAlPO-5 yielded
      benzaldehyde with high toluene conversion. The time on stream study established
      the stability of the catalyst. This catalyst can also be used for the selective
      oxidation of other alkyl aromatics.

PMID- 24734754
TI  - Direct evidence of spatially selective iron mineralization using an immobilized
      ferritin protein cage.
AB  - (Apo)ferritins are cage-shaped proteins which have recently received a great deal
      of attention because the inner cavity of the protein shell can be used as a size
      restricted reaction field for the synthesis of nanomaterials. The
      biomineralization behavior and inorganic nanoparticle (NP) synthesis mechanism of
      (apo)ferritin in solution systems have been studied but the mineralization
      behavior of (apo)ferritin on the substrates has not yet been well studied. Here,
      we conducted quantitative and kinetic analyses of the mineralization behavior of
      immobilized (apo)ferritin on a polyelectrolyte multilayer (PEM) using quartz
      crystal microbalance (QCM), scanning electron microscopy (SEM), and X-ray
      photoelectron spectroscopy (XPS) techniques. We demonstrated that the
      (apo)ferritin immobilized on a substrate synthesizes a ferrihydrite core within
      the confines of the protein cage; similar to a solution dispersed system. In
      addition, we applied a ferritin/apoferritin blended monolayer to the study of
      iron mineralization and revealed that biomineralization in this system is
      spatially selective. It is important to understand the mineralization mechanisms
      for the synthesis of other functional NPs as this approach has potential for a
      broad range of magnetic, catalytic, and biomedical sensing applications.

PMID- 24734755
TI  - Catalytic decomposition of CF4 over iron promoted mesoporous catalysts.
AB  - A series of mesoporous catalysts (MCM-41) promoted by iron nanoparticles were
      prepared by the co-precipitation method and tested for the decomposition of
      carbon tetrafluoride (CF4). The addition of iron oxide nanoparticles to MCM-41
      led to an improvement in the catalytic activity for CF4 decomposition. The
      catalyst was the most active around 5 wt% iron added to MCM-41. Methods of X-ray
      Powder Diffractometer, Scanning Electron Microscope-Energy Dispersive
      Spectrometer, BET, and high resolution transmission electron microscopy were used
      to characterize the MCM-41 catalysts. The analytical results indicated that the
      addition of over 2 wt% iron nanoparticles increased the surface area of MCM-41,
      which was the rate-determining factor of CF4 decomposition over MCM-41 catalyst.
      In conclusion, the addition of iron was responsible for the enhancement of
      catalytic activity of MCM-41.

PMID- 24734756
TI  - Preparation of polysaccharide-apatite hybrid microtubes using layer-by-layer
      assembly and biomimetic mineralization process.
AB  - Organic-inorganic hybrid microtubes were prepared that consisted of
      polysaccharide inner layers and hydroxyapatite (HAp) outer layers. Poly(methyl
      methacrylate) (PMMA) fibers containing small amounts of polyethyleneimine (PEI)
      were used as templates for the layer-by-layer (LbL) assembly of chondroitin
      sulfate C and chitosan. HAp layers were then deposited on polysaccharide layer
      coated fibers using biomimetic processes. PMMA-PEI fiber templates were removed
      by immersing the samples in chloroform. Examination of the resulting materials
      using various physical characterizations such as scanning electron microscopy, FT
      IR spectroscopy, X-ray photoelectron spectroscopy, and X-ray diffraction studies
      supported the successful formation of the hybrid microtubes as designed. The
      results also showed that incorporation of PEI into PMMA fiber matrices was
      effective in inducing HAp deposition. The present procedure can be applied to the
      preparation of various hybrid microtubes consisting of biocompatible organic
      inner layers formed using LbL assemblies and HAp outer layers. Some of these
      hybrids have potential applications in regenerative medicine or tissue
      engineering.

PMID- 24734757
TI  - Interaction of multi-walled carbon nanotubes with water-soluble proteins: effect
      of sidewall carboxylation.
AB  - Effect of sidewall carboxylation on protein adsorption behavior of multi-walled
      carbon nanotubes (MWCNTs) was studied. Two water-soluble proteins, bovine serum
      albumin (BSA) and egg white lysozyme (LYS), were employed in this work.
      Carboxylation of MWCNTs suppressed adsorption of BSA, whereas adsorption of LYS
      was enhanced by the carboxylation. These behaviors are explained by the
      difference in the dominance of hydrophobic interaction and ionic interaction
      between MWCNTs and the proteins.

PMID- 24734759
TI  - Interface structure of niobium carbide-encapsulating carbon nanocapsules studied
      by high-resolution transmission electron microscopy.
AB  - Carbon nanocapsules (CNCs) encapsulating niobium carbide (NbC) crystals with a
      sodium chloride structure were synthesized via a gas-evaporation method by arc
      discharge heating. CNCs were observed by high-resolution transmission electron
      microscopy, and the atomic configurations at the graphene/NbC interfaces were
      investigated. The NbC crystals within the nanospaces of CNCs were truncated by
      the {100}, {110}, and (111} facets and were coated with several graphene layers.
      It was found that the interlayer spacings for the graphene{0001}/NbC{100} and
      graphene{0001}/NbC{110} interfaces were 0.33 +/- 0.05 nm, whereas those for the
      graphene{0001}/{111}NbC interfaces were 0.28 +/- 0.05 nm.

PMID- 24734758
TI  - Collagen/Wollastonite nanowire hybrid scaffolds promoting osteogenic
      differentiation and angiogenic factor expression of mesenchymal stem cells.
AB  - Porous materials and scaffolds have wide applications in biomedical and
      biological fields. They can provide biological and physical cues to promote cell
      adhesion, proliferation, differentiation and extracellular matrix secretion to
      guide new tissue formation. Hybrid scaffolds of collagen and wollastonite
      nanowires with well controlled pore structures were prepared by using ice
      particulates as a porogen material. The hybrid scaffolds had interconnected large
      spherical pores with wollastonite nanowires embedded in the walls of the pores.
      The wollastonite nanowires reinforced the hybrid scaffolds and showed some
      stimulatory effects on cell functions. Human bone marrow-derived mesenchymal stem
      cells showed higher proliferation and osteogenic differentiation and expressed
      higher level of genes encoding angiogenesis-related genes in the hybrid scaffolds
      than did in the collagen scaf-. fold. The results suggest the hybrid scaffolds
      could facilitate osteogenic differentiation and induce angiogenesis and will be
      useful for bone tissue engineering.

PMID- 24734760
TI  - Growth of "waist" ZnO twin rods through hydrothermal synthesis.
AB  - The factors that govern the deposition and structure of "waist" ZnO twin rods
      from aqueous solution through hydrothermal synthesis were discussed in details.
      Pencil-like ZnO hexagonal twin rods were obtained in Zn(2+) + HMTA system on ITO
      glass substrates with ZnO buffer layer deposited in advance. As a contrast, a
      series of experiments were preceded with TBAB or on bare Cu sheet, Zn sheet, and
      Al sheet to research lattice-match influences on ZnO nucleation. A series of
      "waist" ZnO hexagonal twin rods were synthesized and the morphology of each
      "waist" was shown. The forming of different waists results from the different
      lattice-match effects between substrates and ZnO crystal. We demonstrated ZnO
      hexagonal twin rods synthesis on Cu, Al, Zn sheet by normal hydrothermal
      synthesis and revealed different forming schemes of these varying "waists" of the
      twin structures. On the basis of our research, not only some new ways of
      synthesizing ZnO twin rods were proposed but a new idea of applying metal to nano
      devices used in piezoelectric area.

PMID- 24734761
TI  - Physical properties of maleated poly(lactic acid) composites containing different
      functionalized multiwalled carbon nanotubes.
AB  - In the current study, maleic anhydride-grafted poly(lactic acid) (MA-g-PLA) was
      prepared by using a reactive blending method to improve interfacial interaction
      and compatibilization in PLA/functionalized multiwalled carbon nanotube
      nanocomposites. Concentrations of maleic anhydride and initiator were varied at
      3, 5 wt% and 0-0.7 wt%, respectively. The maleation content was determined by
      using a titration method, in which MA-g-PLA containing the optimum degree of
      grafting was subsequently chosen to prepare the nanocomposites containing
      hydroxyl and carboxylic functionalized multiwalled carbon nanotubes at various
      contents (0-5 wt%) and compared with the ones prepared with non-functionalized
      type. Dispersion morphology, thermal and mechanical properties of the resultant
      nanocomposites were investigated by means of transmission electron microscopy,
      differential scanning calorimetry, thermogravimetric analysis, and tensile
      measurement. It was shown that the compatibility between the nanotubes and MA-g
      PLA was improved where the functionalized nanotubes exhibited a better dispersion
      and mechanical property than the nonfunctionalized nanotubes. With increasing
      concentration of carbon nanotubes, tensile strength and Young's modulus of the
      nanocomposites were correspondingly enhanced, in which at 5 wt% addition yielded
      the highest values at 90 MPa and 10 GPa, respectively.

PMID- 24734762
TI  - Study on the methylene blue adsorption from wastewaters by pore-expanded calcium
      fluoride sludge adsorbent.
AB  - The adsorption of methylene blue (MB) onto pore-expanded calcium fluoride sludge
      (ECF) by the batch adsorption technique was investigated. The results showed that
      the adsorption capacity increased with increasing MB concentration but decreased
      as pH was increased. In order to investigate the adsorption mechanisms, three
      simplified isotherm models and kinetic models were used in this study. The best
      fit adsorption isotherm was achieved with the Temkin model. Furthermore, the
      pseudo-second-order kinetic model agreed very well with the dynamical behavior
      for the adsorption of MB onto ECF. Thermodynamic studies revealed that the
      adsorption process of MB onto ECF was spontaneous and exothermic. The results
      indicated that ECF adsorbed MB efficiently and could be used as a waste adsorbent
      for the removal of cationic dyes in wastewater treatment.

PMID- 24734763
TI  - Flexible design of free-standing hybrid polymer nanosheets through bottom-up
      approach.
AB  - We describe the bottom-up design of highly ordered free-standing nanofilms
      consisting of polymer Langmuir-Blodgett films (polymer nanosheets). Polymer
      nanosheets enable the incorporation of a wide variety of functional groups such
      as reactive components and chromophores, which serve as building blocks of free
      standing nanofilms. We demonstrated a free-standing fluorescent hybrid nanofilm
      in which the separation between gold nanoparticles and fluorophores was tuned at
      the nanometer scale. Moreover, we prepared a free-standing nanofilm consisting of
      a two-dimensional homogeneous nickel zinc iron oxide (NiZnFe22O4) nanoparticle
      monolayer assembled on polymer nanosheets.

PMID- 24734764
TI  - Facile electrodeposition of flower like gold nanostructures on a conducting
      polymer support.
AB  - Herein, we report an attractive, simple and templateless synthetic method for the
      formation of anisotropic gold nanostructures. Gold 'mesoflowers' consisting of
      arrays of nanoplatelets were synthesized by electrochemical gold deposition
      on/off conditions onto a conducting poly(diphenylamine) (PDPA) support matrix. A
      possible forming mechanism of anisotropic gold nanostructures is presented. The
      electronic and electrochemical properties of gold nanoflower decorated PDPA in an
      assembled diode configuration were evaluated.

PMID- 24734765
TI  - The influence of oxidation time on the morphologies of TiO2 nanostructures.
AB  - Highly-ordered TiO2 nanostructures have been successfully fabricated by anodic
      oxidation method on the surface of pure titanium and Ti film deposited on the Si
      substrates using 20 V of the DC voltage in 0.5% HF electrolyte. X-ray
      diffractometer (XRD), Raman spectroscopy and field emission scanning electron
      microscope (SEM) were used to characterize the transformations of morphologies
      and structures on the TiO2 nanostructures. The experimental results showed that
      the final morphologies of the nanostructures were time-dependent. The tube
      architectures were firstly fabricated, and with the increase of the oxidation
      time, the tube morphologies were ruined and the rod-like morphologies were
      formed. When the Ti films on the Si substrates were anodized, a new kind of
      porous nanostructures was formed on the surface of the Ti foils, which are
      different to the previous reports. The formation mechanisms of these
      nanostructures were also briefly discussed.

PMID- 24734766
TI  - Synthesis of LiMnPO4 porous plates in mixed solvents system.
AB  - 0.6 to 7.5 microm LiMnPO4 porous plates with pore sizes from 100 to 150 nm were
      successfully synthesized in mixed solvents of ethylene glycol and distilled
      water. By changing stirring time, different morphologies of LiMnPO4 were
      prepared. Porous plates with the percentages of more than 70%, more than 50% and
      25% porous ones were formed in sequence. The according rest parts were particles,
      less than 40% solid plates and 25% solid ones, respectively. Stirring time is the
      key cause influencing the nucleation rate and diffusion rate of the initial
      formed growth units of LiMnPO4. Through adjusting the factor, chemicals with
      specific morphology can be obtained in mixed solvents. The phase composition and
      microstructure were investigated by X-ray diffraction (XRD) and transmission
      electron microscopy (TEM), respectively. This synthetic route provides us a new
      idea to prepare new structure materials.

PMID- 24734767
TI  - Synthesis of porous ZnO in mixed solvents system.
AB  - Three porous structures of ZnO were successfully synthesized in mixed solvents of
      ethylene glycol and distilled water. By adjusting ratios of ethylene glycol and
      distilled water, ZnO morphologies changed. Small porous plates with different
      sizes, folded porous plates with well-proportioned pores, heavily folded porous
      plates and solid flowers without pores emerged in sequence. The mechanism of the
      synthetic process was discussed. The morphologies and microstructures were
      investigated by transmission electron microscopy (TEM). The phase composition was
      verified by X-ray diffraction (XRD). This synthetic route provides a new idea to
      prepare other new structure materials.

PMID- 24734768
TI  - Low temperature growth of double walled carbon nanotubes using FeMoMgO catalyst.
AB  - The chemical vapour deposition technique was utilised to grow the double walled
      carbon nanotubes (DWCNTs) over FeMoMgO catalyst at low temperature (550 degrees
      C) under the mixture of argon, hydrogen and acetylene gas. Thermogravimetric
      analysis revealed that synthesised nanotubes have thermal stability and high
      purity. The high-resolution transmission electron microscopy image showed the
      formation of DWCNTs with tube diameter of 2.5-3.5 nm. We observed radial
      breathing mode (RBM) in Raman spectrum, which is related to the diameter of
      DWCNTs. This synthesis process is simple and economically viable ascribed to low
      synthesis temperature, simplicity and well graphitization with high yield.

PMID- 24734769
TI  - Self-encapsulated core-shell ZnS microspheres: controlled synthesis, growth
      mechanism and photoluminescence properties.
AB  - Self-encapsulated ZnS microspheres with novel cubic structure have been prepared
      at a low temperature. Zinc sulfate and thioacetamide were chosen as raw materials
      in water/ethanol mixed solvents. FESEM images show that the nanostructures
      exhibit a unique geometry consisting of a microsphere core with outer shell of
      nanorods, and the diameter of rods are of about 50 nm. A possible formation
      mechanism is proposed; we think that the agglomeration of ZnS nanocrystals into
      microspheres, and then followed by the polymorph nucleation on the external
      surface are two factors. In the present case, the solvent and the surfactant are
      crucial in the nucleation on the external of the surface of the ZnS microspheres,
      resulting in the formation of nanorod arrays in the shells. Photoluminescence
      shows its strong blue band emission, which may be related to structure defects
      such as point defects that could potentially induce deep-level emission.

PMID- 24734770
TI  - Preparation and characterization of SnO2 and Carbon Co-coated LiFePO4 cathode
      materials.
AB  - The SnO2 and carbon co-coated LiFePO4 cathode materials were successfully
      synthesized by solid state method. The microstructure and morphology of LiFePO4
      composites were characterized by X-ray diffraction, Raman spectroscopy, scanning
      electron microscopy and transmission electron microscope. The results showed that
      the SnO2 and carbon co-coated LiFePO4 cathode materials exhibited more uniform
      particle size distribution. Compared with the uncoated LiFePO4/C, the structure
      of LiFePO4 with SnO2 and carbon coating had no change. The existence of SnO2 and
      carbon coating layer effectively enhanced the initial discharge capacity. Among
      the investigated samples, the one with DBTDL:LiFePO4 molar ratios of 7:100
      exhibited the best electrochemical performance.

PMID- 24734771
TI  - Hydrothermal synthesis of Mo-doped VO2/TiO2 composite nanocrystals with enhanced
      thermochromic performance.
AB  - This paper reports a one-step TiO2 seed-assistant hydrothermal synthesis of Mo
      doped VO2(M)/TiO2 composite nanocrystals. It was found that excess Mo doping can
      promote formation of the VO2(M) phase, and rutile TiO2 seed is beneficial to
      morphology control, size reduction, and infrared modulation of Mo-doped VO2(M)
      nanocrystals. The Mo-doped VO2 nanocrystals epitaxially grow on TiO2 seeds and
      have a quasi-spherical shape with size down to 20 nm and a nearly 35% infrared
      modulation near room temperature. The findings of this work demonstrate important
      progress in the near-room-temperature thermochromic performance of VO2(M)
      nanomaterials, which will find potential application in constructing VO2(M)
      nanocrystal-based smart window coatings. 

PMID- 24734772
TI  - Electrospray ionization-tandem mass spectrometry method for differentiating
      chlorine substitution in disinfection byproduct formation.
AB  - An electrospray ionization-tandem mass spectrometry (ESI-tqMS) method was
      developed to identify the location of chlorine substitution during the
      chlorination of model organic compounds. The chlorine substitution in the
      aliphatic part and that in the benzene ring of an organic molecule can be
      differentiated by their corresponding ranges of optimum collision energies, 5-7
      eV and over 15 eV, respectively, in the precursor ion scan of m/z 35. The method
      was applied to predict the structures of intermediates and reveal the
      transformation pathways during the chlorination of 4-amino-2-chlorobenzoic acid
      and phenylalanine as a function of reaction time and the chlorine-to-precursor
      ratio. In the case of phenylalanine, chlorine was found to replace one hydrogen
      atom attached to the aliphatic nitrogen; in the case of 4-amino-2-chlorobenzoic
      acid, chlorine was found to replace the hydrogen atoms attached to the aromatic
      rings. 

PMID- 24734773
TI  - Daily changes of peak expiratory flow and respiratory symptom occurrence around a
      soy processing factory.
AB  - OBJECTIVES: To evaluate sensitization and acute respiratory health effects in
      inhabitants living in the vicinity of a factory producing soy oil. METHODS: Two
      panels of potential responders were created on the basis of a response to a short
      screening questionnaire sent to random samples of 1,000 exposed and 1,000 non
      exposed individuals living around the factory and a control area. Individuals
      responding to the questionnaire were invited for a medical evaluation, including
      a respiratory symptom questionnaire and skin prick testing, for a panel of common
      allergens and a soy allergen extract. This resulted in 53 atopic and/or asthmatic
      inhabitants from the area surrounding the factory and 30 comparable control
      subjects. In these subjects, morning and evening Peak Expiratory Flow (PEF),
      respiratory symptoms and medication use were recorded daily during a 10-week
      period in the autumn. At the same time, soy allergen and endotoxin concentrations
      were determined in airborne dust in the exposed and the control area. The wind
      direction relative to the location of a subjects' house and the factory was used
      to determine whether an individual was exposed on a particular day. RESULTS: Only
      few of the atopic subjects were sensitized to soy. PEF showed a decrease,
      respiratory symptoms and bronchodilator use, an increase among soy sensitized
      subjects after having been downwind from the factory. Airborne soy allergen was
      found more frequently in the area surrounding the factory and levels were higher
      than in the control area. Highest levels were found on the factory premises. Only
      a weak association was found with wind direction. Airborne endotoxin
      concentrations did not show a consistent pattern with distance, but levels were
      clearly higher on the factory premises. CONCLUSION: Sensitization to soy allergen
      was not increased among the population sample living in the vicinity of the
      factory. Soy sensitized individuals living in the surroundings of the factory
      reported more respiratory symptoms, used bronchodilators more often and had a
      lower PEF after having been downwind of the factory.

PMID- 24734775
TI  - Effect of processing technologies on the allergenicity of food products.
AB  - Heat treatment has been used since ancient times for food processing, first to
      ensure the safety of food and its storage, but also to transform its
      characteristics (in its raw form) and obtain new textures, flavors, or novel
      foods. However, the transformation experienced by food components when heated, or
      processed, can dramatically affect the allergenicity of food, either reducing or
      increasing it. To date, most of the articles published dealing with the changes
      in the potential allergenicity of food are focused on heat treatment and the
      Maillard reaction. However, it is also important to give prominence to other
      group of new technologies developed nowadays, such as high-pressure processing,
      microwaves and food irradiation. These techniques are not likely to replace
      traditional processing methods, but they are becoming attractive for the food
      industry due to different reasons, and it is expected in the near future to have
      different products on the market processed with these new technologies at an
      affordable cost. Moreover, other biochemical modifications, particularly
      enzymatic cross-linking of proteins, have attracted wide-spread attention and
      will be considered as well in this review, because of its great opportunities to
      induce protein modification and thus affect food allergenicity. Together with the
      effect of processing of food allergens, this review will place special attention
      on gastroduodenal digestion of processed allergens, which directly affects their
      allergenicity.

PMID- 24734776
TI  - Attentional capture by spoken language: effects on netballers' visual task
      performance.
AB  - In two experiments, participants performed visual detection, visual
      discrimination and decision-making tasks, in which a binary (left/right) response
      was required. In all experimental conditions, a spoken word ("left"/"right") was
      presented monaurally (left or right ear) at the onset of the visual stimulus. In
      Experiment 1, 26 non-athletes located a target amongst an array of distractors as
      quickly as possible, in both the presence and absence of spoken cues.
      Participants performed superiorly in the presence of valid cues, relative to
      invalid-cue and control conditions. In Experiment 2, 42 skilled netballers
      completed three tasks, in randomised order: a visual detection task, a visual
      discrimination task and a netball decision-making task - all in the presence of
      spoken cues. Our data showed that spoken auditory cues affected not only target
      detection, but also performance on more complex decision-making tasks: cues that
      were either spatially or semantically invalid slowed target detection time;
      spatially invalid cues impaired discrimination task accuracy; and cues that were
      either spatially or semantically valid improved accuracy and speeded decision
      making time in the netball task. When studying visual perception and attention in
      sport, the impact of concomitant auditory information should be taken into
      account in order to achieve a more representative task design.

PMID- 24734777
TI  - Iridium-catalyzed regioselective silylation of secondary alkyl C-H bonds for the
      synthesis of 1,3-diols.
AB  - We report Ir-catalyzed intramolecular silylation of secondary alkyl C-H bonds.
      (Hydrido)silyl ethers, generated in situ by dehydrogenative coupling of a
      tertiary or conformationally restricted secondary alcohol with diethylsilane,
      undergo regioselective silylation at a secondary C-H bond gamma to the hydroxyl
      group. Oxidation of the resulting oxasilolanes in the same vessel generates 1,3
      diols. This method provides a strategy to synthesize 1,3-diols through a hydroxyl
      directed, functionalization of secondary alkyl C-H bonds. Mechanistic studies
      suggest that the C-H bond cleavage is the turnover-limiting step of the catalytic
      cycle. This silylation of secondary C-H bonds is only 40-50 times slower than the
      analogous silylation of primary C-H bonds. 

PMID- 24734774
TI  - Regulation of mucosal immunity in the female reproductive tract: the role of sex
      hormones in immune protection against sexually transmitted pathogens.
AB  - The immune system in the female reproductive tract (FRT) does not mount an attack
      against human immunodeficiency virus (HIV) or other sexually transmitted
      infections (STI) with a single endogenously produced microbicide or with a single
      arm of the immune system. Instead, the body deploys dozens of innate
      antimicrobials to the secretions of the FRT. Working together, these
      antimicrobials along with mucosal antibodies attack viral, bacterial, and fungal
      targets. Within the FRT, the unique challenges of protection against sexually
      transmitted pathogens coupled with the need to sustain the development of an
      allogeneic fetus, has evolved in such a way that sex hormones precisely regulate
      immune function to accomplish both tasks. The studies presented in this review
      demonstrate that estradiol (E2 ) and progesterone secreted during the menstrual
      cycle act both directly and indirectly on epithelial cells, fibroblasts and
      immune cells in the reproductive tract to modify immune function in a way that is
      unique to specific sites throughout the FRT. As presented in this review, studies
      from our laboratory and others demonstrate that the innate and adaptive immune
      systems are under hormonal control, that protection varies with the stage of the
      menstrual cycle and as such, is dampened during the secretory stage of the cycle
      to optimize conditions for fertilization and pregnancy. In doing so, a window of
      STI vulnerability is created during which potential pathogens including HIV enter
      the reproductive tract to infect host targets. 

PMID- 24734778
TI  - Response to the letter to the editor.

PMID- 24734779
TI  - Prediction of large-gap two-dimensional topological insulators consisting of
      bilayers of group III elements with Bi.
AB  - We use first-principles electronic structure calculations to predict a new class
      of two-dimensional (2D) topological insulators (TIs) in binary compositions of
      group III elements (B, Al, Ga, In, and Tl) and bismuth (Bi) in a buckled
      honeycomb structure. We identify band inversions in pristine GaBi, InBi, and TlBi
      bilayers, with gaps as large as 560 meV, making these materials suitable for room
      temperature applications. Furthermore, we demonstrate the possibility of strain
      engineering in that the topological phase transition in BBi and AlBi could be
      driven at ~6.6% strain. The buckled structure allows the formation of two
      different topological edge states in the zigzag and armchair edges. More
      importantly, isolated Dirac-cone edge states are predicted for armchair edges
      with the Dirac point lying in the middle of the 2D bulk gap. A room-temperature
      bulk band gap and an isolated Dirac cone allow these states to reach the long
      sought topological spin-transport regime. Our findings suggest that the buckled
      honeycomb structure is a versatile platform for hosting nontrivial topological
      states and spin-polarized Dirac fermions with the flexibility of chemical and
      mechanical tunability. 

PMID- 24734780
TI  - Measurement of nonsulfated cholecystokinins.
AB  - Most proteins undergo posttranslational modifications that govern the function of
      the protein. In synchrony, correspondingly unmodified proteins that are
      functionally silent or act differently may also be synthesized. The gut hormone
      precursor, procholecystokinin (proCCK) is an example of a protein that is heavily
      modified. An essential modification is O-sulfation of Y77, which is necessary for
      the gallbladder emptying effect of CCK peptides via the CCKA-receptor. In order
      to examine possible in vivo synthesis also of nonsulfated CCK, we have
      established a two-step analysis that requires tryptic cleavage at a defined
      processing site in proCCK (R75-D76) followed by monospecific RIA-measurement of
      the then exposed nonsulfated N-terminal sequence of CCK-8 (DYMGW...). The
      analysis shows that endocrine cells in the gut synthesize nonsulfated CCK
      peptides (-58, -33, -22, and -8) in the order of 20-35% of the corresponding
      sulfated CCKs. Since nonsulfated CCK peptides are full agonists of the CCKB
      receptor, the assay has revealed a hitherto unrecognized gut hormonal peptide
      system. The assay may prove useful in the diagnosis and control of diseases with
      hyperCCKemia. This includes CCK-producing neuroendocrine tumors such as the
      recently described CCKomas and medullary thyroid C-cell carcinomas.

PMID- 24734781
TI  - Ultrastructural characterization of mesenchymal stromal cells labeled with
      ultrasmall superparamagnetic iron-oxide nanoparticles for clinical tracking
      studies.
AB  - INTRODUCTION: To evaluate survival and engraftment of mesenchymal stromal cells
      (MSCs) in vivo, it is necessary to track implanted cells non-invasively with a
      method, which does not influence cellular ultrastructure and functional
      characteristics. Iron-oxide particles have been applied for cell tracking for
      years, but knowledge regarding possible cytotoxic ultrastructural changes
      subsequent to iron-oxide particle labeling is limited. Hence, the purpose of this
      study was to label MSCs with dextran-coated ultrasmall super-paramagnetic iron
      oxide (USPIO) particles conjugated with the transduction sequence of trans
      activator of transcription (TAT) (IODEX-TAT) and evaluate the effect of labeling
      on ultrastructure, viability, phenotype and proliferative capacity of the cells.
      MATERIALS AND METHODS: MSCs were labeled with 5 and 10 MUg IODEX-TAT/10(5) cells
      for 2, 6 and 21 hours. IODEX-TAT uptake and cellular ultrastructure were
      determined by electron microscopy. Cell viability was determined by propidium
      iodide staining and cell proliferation capacity by 5-bromo-2-deoxyuridine (BrdU)
      incorporation. Maintenance of stem cell surface markers was determined by flow
      cytometry. Results. IODEX-TAT labeling for 2, 6 and 21 h did not influence
      cellular ultrastructure or viability. Moreover, neither stem cell surface markers
      nor cell proliferation capacity was affected by labeling with IODEX-TAT.
      CONCLUSION: Our results demonstrate that labeling of MSCs for 21 h with a
      clinically relevant dose of 10 MUg IODEX-TAT/10(5) cells is feasible and does not
      affect MSC ultrastructure, viability, phenotype or proliferation capacity.

PMID- 24734782
TI  - The influence of the gastrointestinal tract and the liver on cystatin C serum
      concentrations.
AB  - OBJECTIVE: The purpose of this study in humans was to examine the influence of
      the gastrointestinal tract and liver on the serum concentrations of cystatin C.
      METHODS: Eighteen healthy volunteers and 28 patients suspected of having chronic
      intestinal ischemia underwent catheterization of the abdominal aorta and the
      central hepatic vein. Blood samples were taken simultaneously from the abdominal
      aorta and the central hepatic vein 60, 90 and 120 minutes after the start of the
      investigation. After the first blood sample, a standard liquid meal was ingested.
      Measurement of splanchnic blood flow was performed using the Fick principle with
      constant infusion of (99m)Tc-Bridatec. Angiography was performed at the end of
      the investigation. RESULTS: The splanchnic blood flow increased significantly
      postprandially in the healthy volunteers and in the patients with normal
      angiography by 0.613-0.698 L/min and increased non- significantly in the patients
      with abnormal angiography (n = 5) by 0.135 L/min on average. ANOVA and the
      Bonferroni's multiple comparison test showed no significant difference between
      the means of cystatin C, creatinine or urea in the samples taken 60, 90 and 120
      minutes after the start of the investigation in the abdominal aorta and the
      hepatic vein in the healthy volunteers or in the patients suspected of chronic
      intestinal ischemia with normal angiography. CONCLUSION: There was no indication
      of hepatic elimination of cystatin C, creatinine or urea. The serum
      concentrations of cystatin C, creatinine and urea in the central hepatic vein and
      the abdominal aorta were independent of the splanchnic blood flow.

PMID- 24734783
TI  - H-bonding vs non-H-bonding in 100% pyrene methacrylate comb polymers: self
      assembly probed by time-resolved emission spectra and temperature dependent
      fluorescence.
AB  - The differences in self-organization behavior in novel 100% pyrene labeled comb
      methacrylate polymers probed as a function of their varied origins of excimer
      formation are presented. The different structural variations in the polymers
      included the presence or absence of hydrogen bonding interactions in the form of
      urethane linkages, short or long alkyl spacer segments separating the pyrene
      units from the polymer backbone and linear versus kinked urethane linkage. The
      effect of variable concentration and temperature on the chemical shift of the NH
      proton of the urethane linkage was probed using (1)H NMR experiments conducted at
      temperatures varying from 25 to 70  degrees C at two different concentrations
      (2.5 and 25 mmol) in DMSO-d6 as solvent. The photophysical properties of the
      polymers in dilute DMF solutions were investigated by steady state emission,
      fluorescence decay studies, time-resolved emission spectra (TRES), and variable
      temperature emission studies. It was observed that the polymer poly(PBH) having a
      non-hydrogen-bondable ester linkage in the pendant chains formed an excimer
      completely via a static mechanism and the ground state aggregate species were not
      broken even at higher temperatures. The polymer poly(PIC) having a short hydrogen
      bondable urethane linkage formed an excimer via a static as well as dynamic
      mechanism. The other hydrogen-bondable urethane methacrylate polymers having a
      linear linker poly(PHH) and kinked linker (PIHP) formed excimer mostly via a
      dynamic mechanism with a very small contribution from the static route. The TRES
      studies carried out for the polymers provided significant insight into the
      excimer formation mechanism in these polymers. The variable temperature
      fluorescence studies highlighted the differences in the H-bonded vs non-H-bonded
      polymer as a function of their excimer recovery upon cooling. 

PMID- 24734784
TI  - Species-specific alternative splicing leads to unique expression of sno-lncRNAs.
AB  - BACKGROUND: Intron-derived long noncoding RNAs with snoRNA ends (sno-lncRNAs) are
      highly expressed from the imprinted Prader-Willi syndrome (PWS) region on human
      chromosome 15. However, sno-lncRNAs from other regions of the human genome or
      from other genomes have not yet been documented. RESULTS: By exploring non
      polyadenylated transcriptomes from human, rhesus and mouse, we have
      systematically annotated sno-lncRNAs expressed in all three species. In total,
      using available data from a limited set of cell lines, 19 sno-lncRNAs have been
      identified with tissue- and species-specific expression patterns. Although
      primary sequence analysis revealed that snoRNAs themselves are conserved from
      human to mouse, sno-lncRNAs are not. PWS region sno-lncRNAs are highly expressed
      in human and rhesus monkey, but are undetectable in mouse. Importantly, the
      absence of PWS region sno-lncRNAs in mouse suggested a possible reason why
      current mouse models fail to fully recapitulate pathological features of human
      PWS. In addition, a RPL13A region sno-lncRNA was specifically revealed in mouse
      embryonic stem cells, and its snoRNA ends were reported to influence lipid
      metabolism. Interestingly, the RPL13A region sno-lncRNA is barely detectable in
      human. We further demonstrated that the formation of sno-lncRNAs is often
      associated with alternative splicing of exons within their parent genes, and
      species-specific alternative splicing leads to unique expression pattern of sno
      lncRNAs in different animals. CONCLUSIONS: Comparative transcriptomes of non
      polyadenylated RNAs among human, rhesus and mouse revealed that the expression of
      sno-lncRNAs is species-specific and that their processing is closely linked to
      alternative splicing of their parent genes. This study thus further demonstrates
      a complex regulatory network of coding and noncoding parts of the mammalian
      genome.

PMID- 24734785
TI  - Enzyme-modified starch as an oil delivery system for bake-only chicken nuggets.
AB  - This study investigated the effects of enzyme modification on starch as an
      effective oil delivery system for bake-only chicken nuggets. Various native
      starches were hydrolyzed by amyloglucosidase to a hydrolysis degree of 20% to 25%
      and plated with 50% (w/w, starch dry basis) with canola oil to create a starch
      oil matrix. This matrix was then blended into a dry ingredient blend for batter
      and breader components. Nuggets were prepared by coated with predust, hydrated
      batter, and breader, and the coated nuggets were steam-baked until fully cooked
      and then frozen until texture and sensory analyses. The enzyme-modified starches
      showed a significant decrease in pasting viscosities for all starch types. For
      textural properties of nuggets, no clear relationship was found between peak
      force and starch source or amylose content. Sensory attributes related to fried
      foods (for example, crispness and mouth-coating) did not significantly differ
      between bake-only nuggets formulated using the enzyme-modified starches and the
      partially fried and baked ones. The present findings suggest that enzyme-modified
      starches can deliver sufficient quantity of oil to create sensory attributes
      similar to those of partially fried chicken nuggets. Further study is needed to
      optimize the coating formulation of bake-only chicken nugget to become close to
      the fried one in sensory aspects. PRACTICAL APPLICATION: The food industry has
      become increasingly focused on healthier items. Frying imparts several critical
      and desirable product functionalities, such as developing texture and color, and
      providing mouth-feel and flavor. The food industry has yet to duplicate all of
      the unique characteristics of fried chicken nuggets with a baking process. This
      study investigated the application of enzyme-modified starch as an oil delivery
      system in bake-only chicken nugget formulation in attempts to provide
      characteristics of fried items. This information is useful to improve the
      nutritional value of fried food by eliminating the frying process while
      preserving the desired characteristics of fried products.

PMID- 24734786
TI  - Efficient generation of human embryonic stem cell-derived cardiac progenitors
      based on tissue-specific enhanced green fluorescence protein expression.
AB  - Cardiac progenitor cells (CPCs) are committed to the cardiac lineage but retain
      their proliferative capacity before becoming quiescent mature cardiomyocytes
      (CMs). In medical therapy and research, the use of human pluripotent stem cell
      derived CPCs would have several advantages compared with mature CMs, as the
      progenitors show better engraftment into existing heart tissues, and provide
      unique potential for cardiovascular developmental as well as for pharmacological
      studies. Here, we demonstrate that the CAG promoter-driven enhanced green
      fluorescence protein (EGFP) reporter system enables the identification and
      isolation of embryonic stem cell-derived CPCs. Tracing of CPCs during
      differentiation confirmed up-regulation of surface markers, previously described
      to identify cardiac precursors and early CMs. Isolated CPCs express cardiac
      lineage-specific transcripts, still have proliferating capacity, and can be re
      aggregated into embryoid body-like structures (CAG-EGFP(high) rEBs). Expression
      of troponin T and NKX2.5 mRNA is up-regulated in long-term cultured CAG
      EGFP(high) rEBs, in which more than 90% of the cells become Troponin I positive
      mature CMs. Moreover, about one third of the CAG-EGFP(high) rEBs show spontaneous
      contractions. The method described here provides a powerful tool to generate
      expandable cultures of pure human CPCs that can be used for exploring early
      markers of the cardiac lineage, as well as for drug screening or tissue
      engineering applications. 

PMID- 24734787
TI  - Effect of sitting position on equal-dose spinal anaesthetic for caesarean section
      and post-partum tubal ligation.
AB  - BACKGROUND: We studied the hypothesis that an equal spinal anaesthetic dose
      administered in the sitting position to patients undergoing post-partum tubal
      ligation (PPTL) and caesarean section (CS) would yield similar sensory block
      characteristics and analgesic efficacy. METHODS: This prospective, non-randomised
      trial recruited 20 women undergoing PPTL within 48 h of vaginal delivery and 20
      undergoing CS. Spinal anaesthesia comprising intrathecal hyperbaric bupivacaine
      12 mg and morphine 100 MUg was administered at L3/4 with patients sitting. Our
      primary end point was the maximal dermatomal sensory block (to cold). RESULTS:
      Baseline demographics were comparable, but PPTL patients had greater parity, with
      mean +/- standard deviation 17.54 +/- 11.2 h from delivery to spinal anaesthesia,
      and shorter duration of surgery, 17.54 +/- 11.2 vs. 40.3 +/- 15.5 min. Similar
      maximal sensory blocks (to cold) were achieved in group PPTL vs. CS, T4 (T1-T5)
      vs. T3 (T1-T5), P = 0.104, in comparable times, 8.6 +/- 2.6 vs. 7.6 +/- 3.0 min,
      P = 0.267. PPTL patients had significantly faster two-segment block regression
      (70.7 +/- 23.5 vs. 97.6 +/- 23.9 min, P = 0.001) and to T10 (120.8 +/- 35.6 vs.
      145.1 +/- 24.3 min, P = 0.016), with less hypotension (25% vs. 65%, P = 0.025)
      and phenylephrine (20.0 +/- 60.6 MUg vs. 120.0 +/- 119.6 MUg, P = 0.005).
      CONCLUSION: The same dose of hyperbaric bupivacaine 12 mg and morphine 100 MUg
      administered in the sitting position to both PPTL and CS parturients yielded
      similar maximal sensory blocks, but PPTL exhibited faster block regression and
      less hypotension/vasopressor requirement.

PMID- 24734788
TI  - Childhood psychosocial development and fatal injuries in Gauteng, South Africa.
AB  - BACKGROUND: In South Africa, injuries are the third leading cause of death and
      disability. Children are especially susceptible to unintentional injuries,
      especially pedestrian injuries, burns and drowning. Injury risk is informed by
      children's exposure to adverse environmental circumstances, and individual
      capacities dependent on developmental maturity. Boys are at greater risk than
      girls. This study investigates the incidence of fatal childhood injuries as well
      as sex differences across psychosocial development stages. METHODS: Data on fatal
      injuries in Gauteng, South Africa's most populous province, were obtained from
      the National Injury Mortality Surveillance System. The analysis drew on Erikson's
      psychosocial theory of development which was used to create meaningful age
      groups. Age-specific population data from the 2011 Census were used to calculate
      rates, and significant differences were determined through the generation of risk
      ratios and confidence intervals. RESULTS: There were 5404 fatal injuries among
      children in Gauteng from 2008 to 2011. The average age of victims was 8.9 years,
      and the majority male (65.6%). In infancy, the mortality rates for all injuries
      and non-traffic unintentional injuries were significantly higher than for the
      other age groups. Burns were the most common cause of death in infancy and early
      childhood. Pedestrian injuries accounted for a third of mortality in preschool
      and school age, and homicide rates were significantly higher in adolescence than
      in the other developmental stages. For injuries in general, boys had
      significantly higher mortality rates than girls in all age groups except
      preschool. The only instance where the mortality rate for girls was significantly
      higher than for boys was for adolescent ingestion poisoning suicides.
      CONCLUSIONS: The exposure to environmental and social risks is differentially
      moderated with maturing age and levels of autonomy. The sex of the child also
      informs risk. The nature of these risks is important when considering child
      injury prevention strategies.

PMID- 24734789
TI  - Nurses' voices amplify reality of staff shortages.

PMID- 24734791
TI  - Nurses say patients still neglected because of inadequate staff levels.

PMID- 24734794
TI  - Study shows no progress in past decade for BME nursing directors.

PMID- 24734796
TI  - Increase in nurse numbers linked to better patient survival rates in ICU.

PMID- 24734804
TI  - Nurse training places creeping up after dire warnings of shortages.

PMID- 24734805
TI  - Divide and conquer: how to dismantle the NHS.

PMID- 24734811
TI  - Care homes: managing medicines.

PMID- 24734812
TI  - Added values.
AB  - Values-based interviewing is an approach to recruitment that focuses on the job
      applicant's attitudes and behaviours and whether they are a good 'fit' for the
      organization.Used successfully by hospitals in the United States, the approach is
      being introduced to some NHS trusts.

PMID- 24734813
TI  - The dark side of night shifts.
AB  - A growing body of evidence shows that night work can have a negative effect on
      health. With the NHS moving towards providing a seven-day, 24-hour service, more
      nurses may be required to work nights. Employers will have to take action to
      mitigate the potentially damaging effects.

PMID- 24734826
TI  - Loss of NHS direct will pile more pressure on health services.

PMID- 24734827
TI  - Sign the e-petition and respond to the RCN consultation on pay.

PMID- 24734828
TI  - If we do not stand up for ourselves, how can we battle for our patients?

PMID- 24734829
TI  - MPs and nurses both serve the public - so pay them the same.

PMID- 24734830
TI  - What could go wrong that the NMC needs so much in reserves?

PMID- 24734832
TI  - 'Normal' anxiety is being treated as a chronic medical condition.

PMID- 24734833
TI  - Anxiety, particularly in young women, needs to be addressed.

PMID- 24734836
TI  - Managing Clostridium difficile infection in hospitalised patients.
AB  - Checklists are not a new phenomenon and have been used in the aviation industry
      for some time as a means of ensuring safety and minimising harm. Checklists are
      now used commonly in health care to improve patient safety. This article
      describes the development and integration of a daily review checklist process to
      support the care and management of patients with Clostridium difficile infection
      in one NHS trust hospital. The aim of the checklist is to assist staff in early
      recognition of disease severity, identification of potential complications and
      prevention of cross-transmission of C.difficile. 

PMID- 24734837
TI  - Nervous system: part 3.
AB  - This article, which forms part of the life sciences series and is the last of
      three articles on the nervous system, explores the major divisions of the
      peripheral nervous system. Motor and sensory nerves will be described before a
      more detailed examination of the cranial and spinal nerves is provided. The
      autonomic nervous system will be explored, including the diverse roles of the
      parasympathetic and sympathetic divisions. The role of spinal reflexes in
      maintaining homeostasis is identified. Motor neurone disease will be discussed
      briefly as an example of a disorder of the peripheral nervous system. 

PMID- 24734838
TI  - Varicella zoster virus: chickenpox and shingles.
AB  - The varicella zoster virus causes two infections: varicella, also known as
      chickenpox occurring mostly in childhood, and herpes zoster, also known as
      shingles affecting mainly older people. Varicella usually occurs in children
      under ten years of age. It is generally a mild infection and in the UK
      vaccination is not offered as part of the routine immunisation programme.
      However, adults who develop varicella are at risk of developing complications and
      the infection is likely to be more severe. Serious complications are a particular
      risk for pregnant women, unborn children, neonates and those who are
      immunocompromised. Nurses whose work brings them into contact with those at risk
      have a vital role in providing information about the importance of avoiding
      varicella. After the acute infection, the varicella zoster virus gains access to
      the ganglia in the sensory nervous system where it can remain dormant for years.
      Reactivation results in herpes zoster, a common and unpleasant illness. A vaccine
      for herpes zoster was introduced for people aged 70-79 in the UK in September
      2013. 

PMID- 24734839
TI  - Psychosis.

PMID- 24734840
TI  - Setting the standard.

PMID- 24734841
TI  - What makes you so specialist?

PMID- 24734844
TI  - Bridging the theoretical gap.

PMID- 24734845
TI  - Secular trends in Cherokee cranial morphology: Eastern vs Western bands.
AB  - BACKGROUND: The research objective was to examine if secular trends can be
      identified for cranial data commissioned by Boas in 1892, specifically for
      cranial breadth and cranial length of the Eastern and Western band Cherokee who
      experienced environmental hardships. MATERIALS AND METHODS: Multiple regression
      analysis was used to test the degree of relationship between each of the cranial
      measures: cranial length, cranial breadth and cephalic index, along with
      predictor variables (year-of-birth, location, sex, admixture); the model revealed
      a significant difference for all craniometric variables. Additional regression
      analysis was performed with smoothing Loess plots to observe cranial length and
      cranial breadth change over time (year-of-birth) separately for Eastern and
      Western Cherokee band females and males born between 1783-1874. RESULTS: This
      revealed the Western and Eastern bands show a decrease in cranial length over
      time. Eastern band individuals maintain a relatively constant head breadth, while
      Western Band individuals show a sharp decline beginning around 1860. CONCLUSIONS:
      These findings support negative secular trend occurring for both Cherokee bands
      where the environment made a detrimental impact; this is especially marked with
      the Western Cherokee band.

PMID- 24734846
TI  - What's in this issue?

PMID- 24734847
TI  - Recent advances in understanding pain: what lies ahead for critical care?

PMID- 24734848
TI  - Providing compassionate care to patients waiting on Emergency Department
      trolleys: can we do more?

PMID- 24734849
TI  - Rationales of restricted visiting hour in Iranian intensive care units: a
      qualitative study.
AB  - BACKGROUND: Today, critical care visitation is considered an important aspect of
      patient-centred care and its positive effects on patients and their relatives
      have been demonstrated. However, restricted visiting hours in the intensive care
      units (ICUs) is often an adopted norm. The reasons for such restricted policies
      in Iran still remain unknown. OBJECTIVES: The purpose of this study was to
      identify the rationales for restricted visiting hours in adult ICUs in Iran.
      METHODS: A qualitative design using a thematic analysis approach was used for
      data gathering and analysis. Participants in this study were six nurses, three
      head nurses, two patients and four visitors. They were chosen through purposive
      sampling method. Data were gathered through semi-structured individual
      interviews. FINDINGS: The data analysis resulted in three themes: 'health
      protection', 'safety promotion' and 'privacy preservation'. CONCLUSION: The
      result showed that through restricted visiting hours, nurses try to protect
      vulnerable ICU patients from physical, psychological and legal risk. Although the
      ICU nurses' concerns seem reasonable in some cases, a review of visiting policies
      in order to meet the needs of patients and their families is essential. RELEVANCE
      TO CLINICAL PRACTICE: Effective supervision by charge nurses and regulation of
      environmental activities with visiting hours can resolve many concerns. Health
      care professionals, especially nurses, are required to create the conditions in
      which patients' family members are informed about the patients' health status and
      patients can be visited in suitable ward conditions.

PMID- 24734854
TI  - Effect of cleansing of biofilm formed on titanium discs.
AB  - OBJECTIVES: To study the combined effect of mechanical and chemical cleansing on
      a 4-day biofilm grown intra-orally on titanium discs with different surface
      characteristics. MATERIAL AND METHODS: Twenty subjects used a splint with two
      metal plates in the upper jaw. Each plate was placed in the premolar-molar region
      and carried four titanium discs with four different surface characteristics
      (OsseoSpeed(TM), TiOblast(TM), experimental and turned surface). After 4 days of
      biofilm growth, the discs were cleaned mechanically and chemically with saline or
      chlorhexidine. Following cleansing, microbial samples were obtained and analysed
      by culture. The titanium discs were processed for scanning electron microscope
      (SEM) analysis. The experiment was repeated 3 days later using delmopinol or a
      mixture of essential oils during cleansing. RESULTS: The combination of
      mechanical and chemical cleansing was ineffective in complete biofilm removal
      from all four titanium discs. The microbiological analysis did not reveal any
      statistically significant differences between surface types or between cleaning
      agents regarding logarithmic mean counts of CFU for specific bacteria, aerobes,
      anaerobes or the TVC. Aerobes were more numerous than anaerobes on all surface
      types. The SEM analysis disclosed that the remaining biofilm on moderately rough
      surfaces (OsseoSpeed(TM), TiOblast(TM) and experimental) was complex and firmly
      attached, while the biofilm on turned surface had a pattern of spread bacteria
      forming less clusters. CONCLUSIONS: Cleansing may call for prolonged time of
      chemomechanical debridement and/or more effective disinfectants to suppress
      biofilms on dental implant surfaces.

PMID- 24734855
TI  - Why self-care pain medicine?

PMID- 24734856
TI  - The current state of the science for active self-care complementary and
      integrative medicine therapies in the management of chronic pain symptoms:
      lessons learned, directions for the future.
AB  - OBJECTIVES: Chronic pain management typically consists of prescription
      medications or provider-based, behavioral, or interventional procedures which are
      often ineffective, may be costly, and can be associated with undesirable side
      effects. Because chronic pain affects the whole person (body, mind, and spirit),
      patient-centered complementary and integrative medicine (CIM) therapies that
      acknowledge the patients' roles in their own healing processes have the potential
      to provide more efficient and comprehensive chronic pain management. Active self
      care CIM (ACT-CIM) therapies allow for a more diverse, patient-centered treatment
      of complex symptoms, promote self-management, and are relatively safe and cost
      effective. To date, there are no systematic reviews examining the full range of
      ACT-CIM used for chronic pain symptom management. METHODS: A systematic review
      was conducted, using Samueli Institute's rapid evidence assessment of the
      literature methodology, to rigorously assess both the quality of the research on
      ACT-CIM modalities and the evidence for their efficacy and effectiveness in
      treating chronic pain symptoms. A working group of subject matter experts was
      also convened to evaluate the overall literature pool and develop recommendations
      for the use and implementation of these modalities. RESULTS: Following key
      database searches, 146 randomized controlled trials were included in the review.
      CONCLUSION: This article summarizes the current state of the science, lessons
      learned from the gaps exposed by the review, as well as suggestions for next
      steps toward translation for the field. Although the review's entire scope is
      detailed throughout the current Pain Medicine supplement, the authors encourage
      the use of this report as a guide for future ACT-CIM research.

PMID- 24734857
TI  - Mind-body therapies for the self-management of chronic pain symptoms.
AB  - OBJECTIVES: Chronic pain management typically consists of prescription
      medications or provider-based, behavioral, or interventional procedures which are
      often ineffective, may be costly, and can be associated with undesirable side
      effects. Because chronic pain affects the whole person (body, mind, and spirit),
      patient-centered complementary and integrative medicine (CIM) therapies that
      acknowledge the patients' roles in their own healing processes have the potential
      to provide more efficient and comprehensive chronic pain management. Active self
      care complementary and integrative medicine (ACT-CIM) therapies allow for a more
      diverse, patient-centered treatment of complex symptoms, promote self-management,
      and are relatively safe and cost-effective. To date, there are no systematic
      reviews examining the full range of ACT-CIM used for chronic pain symptom
      management. METHODS: A systematic review was conducted, using Samueli Institute's
      rapid evidence assessment of the literature (REAL(c)) methodology, to rigorously
      assess both the quality of the research on ACT-CIM modalities and the evidence
      for their efficacy and effectiveness in treating chronic pain symptoms. A panel
      of subject matter experts was also convened to evaluate the overall literature
      pool and develop recommendations for the use and implementation of these
      modalities. RESULTS: Following key database searches, 146 randomized controlled
      trials were included in the review, 54 of which investigated mind-body therapies,
      as defined by the authors. CONCLUSIONS: This article summarizes the current
      evidence, quality, efficacy, and safety of these modalities. Recommendations and
      next steps to move this field of research forward are also discussed. The entire
      scope of the review is detailed throughout the current Pain Medicine supplement.

PMID- 24734858
TI  - Call to action: "if not now, when? If not you, who?".

PMID- 24734859
TI  - Movement therapies for the self-management of chronic pain symptoms.
AB  - OBJECTIVES: Chronic pain management typically consists of prescription
      medications or provider-based, behavioral, or interventional procedures which are
      often ineffective, may be costly, and can be associated with undesirable side
      effects. Because chronic pain affects the whole person (body, mind, and spirit),
      patient-centered complementary and integrative medicine (CIM) therapies that
      acknowledge the patients' roles in their own healing processes have the potential
      to provide more efficient and comprehensive chronic pain management. Active self
      care CIM therapies (ACT-CIM) allow for a more diverse, patient-centered treatment
      of complex symptoms, promote self-management, and are relatively safe and cost
      effective. To date, there are no systematic reviews examining the full range of
      ACT-CIM used for chronic pain symptom management. METHODS: A systematic review
      was conducted, using Samueli Institute's rapid evidence assessment of the
      literature methodology, to rigorously assess both the quality of the research on
      ACT-CIM modalities and the evidence for their efficacy and effectiveness in
      treating chronic pain symptoms. A working group of subject matter experts was
      also convened to evaluate the overall literature pool and develop recommendations
      for the use and implementation of these modalities. RESULTS: Following key
      database searches, 146 randomized controlled trials were included in the review,
      30 of which investigated movement therapies, as defined by the authors.
      CONCLUSIONS: This article summarizes the current evidence, quality, efficacy, and
      safety of these modalities. Recommendations and next steps to move this field of
      research forward are also discussed. The entire scope of the review is detailed
      throughout the current Pain Medicine supplement.

PMID- 24734860
TI  - Physically oriented therapies for the self-management of chronic pain symptoms.
AB  - OBJECTIVES: Chronic pain management typically consists of prescription
      medications or provider-based, behavioral, or interventional procedures that are
      often ineffective, may be costly, and can be associated with undesirable side
      effects. Because chronic pain affects the whole person (body, mind, and spirit),
      patient-centered complementary and integrative medicine (CIM) therapies that
      acknowledge the patients' roles in their own healing processes have the potential
      to provide more efficient and comprehensive chronic pain management. Active self
      care CIM (ACT-CIM) therapies allow for a more diverse, patient-centered treatment
      of complex symptoms, promote self-management, and are relatively safe and cost
      effective. To date, there are no systematic reviews examining the full range of
      ACT-CIM used for chronic pain symptom management. METHODS: A systematic review
      was conducted, using Samueli Institute's Rapid Evidence Assessment of the
      Literature methodology, to rigorously assess both the quality of the research on
      ACT-CIM modalities and the evidence for their efficacy and effectiveness in
      treating chronic pain symptoms. A working group of subject matter experts was
      also convened to evaluate the overall literature pool and develop recommendations
      for the use and implementation of these modalities. RESULTS: Following key
      database searches, 146 randomized controlled trials were included in the review,
      10 of which investigated physically oriented therapies, as defined by the
      authors. CONCLUSION: This article summarizes the current evidence, quality,
      efficacy, and safety of these modalities. Recommendations and next steps to move
      this field of research forward are also discussed. The entire scope of the review
      is detailed throughout the current Pain Medicine supplement.

PMID- 24734861
TI  - Sensory art therapies for the self-management of chronic pain symptoms.
AB  - OBJECTIVES: Chronic pain management typically consists of prescription
      medications or provider-based, behavioral, or interventional procedures which are
      often ineffective, may be costly, and can be associated with undesirable side
      effects. Because chronic pain affects the whole person (body, mind, and spirit),
      patient-centered complementary and integrative medicine (CIM) therapies that
      acknowledge the patients' roles in their own healing processes have the potential
      to provide more efficient and comprehensive chronic pain management. Active self
      care CIM therapies (ACT-CIM) allow for a more diverse, patient-centered treatment
      of complex symptoms, promote self-management, and are relatively safe and cost
      effective. To date, there are no systematic reviews examining the full range of
      ACT-CIM used for chronic pain symptom management. METHODS: A systematic review
      was conducted, using Samueli Institute's rapid evidence assessment of the
      literature methodology, to rigorously assess both the quality of the research on
      ACT-CIM modalities and the evidence for their efficacy and effectiveness in
      treating chronic pain symptoms. A working group of subject matter experts was
      also convened to evaluate the overall literature pool and develop recommendations
      for the use and implementation of these modalities. RESULTS: Following key
      database searches, 146 randomized controlled trials were included in the review,
      eight of which investigated sensory art therapies, as defined by the authors.
      CONCLUSIONS: This article summarizes the current evidence, quality, efficacy, and
      safety of these modalities. Recommendations and next steps to move this field of
      research forward are also discussed. The entire scope of the review is detailed
      throughout the current Pain Medicine supplement.

PMID- 24734862
TI  - Patients' use of active self-care complementary and integrative medicine in their
      management of chronic pain symptoms.

PMID- 24734863
TI  - Multimodal, integrative therapies for the self-management of chronic pain
      symptoms.
AB  - OBJECTIVES: Chronic pain management typically consists of prescription
      medications or provider-based, behavioral, or interventional procedures which are
      often ineffective, may be costly, and can be associated with undesirable side
      effects. Because chronic pain affects the whole person (body, mind, and spirit),
      patient-centered complementary and integrative medicine (CIM) therapies that
      acknowledge the patients' roles in their own healing processes have the potential
      to provide more efficient and comprehensive chronic pain management. Active self
      care CIM therapies (ACT-CIM) allow for a more diverse, patient-centered treatment
      of complex symptoms, promote self-management, and are relatively safe and cost
      effective. To date, there are no systematic reviews examining the full range of
      ACT-CIM used for chronic pain symptom management. METHODS: A systematic review
      was conducted, using Samueli Institute's rapid evidence assessment of the
      literature methodology, to rigorously assess both the quality of the research on
      ACT-CIM modalities and the evidence for their efficacy and effectiveness in
      treating chronic pain symptoms. A working group of subject matter experts was
      also convened to evaluate the overall literature pool and develop recommendations
      for the use and implementation of these modalities. RESULTS: Following key
      database searches, 146 randomized controlled trials were included in the review,
      26 of which investigated multimodal, integrative therapies, as defined by the
      authors. CONCLUSION: This article summarizes the current evidence, quality, and
      effectiveness of these modalities. Recommendations and next steps to move this
      field of research forward are also discussed. The entire scope of the review is
      detailed throughout the current Pain Medicine supplement.

PMID- 24734864
TI  - Effectiveness of active self-care complementary and integrative medicine
      therapies: options for the management of chronic pain symptoms.
AB  - OBJECTIVES: Chronic pain management typically consists of prescription
      medications or provider-based, behavioral, or interventional procedures that are
      often ineffective, may be costly, and can be associated with undesirable side
      effects. Because chronic pain affects the whole person (body, mind, and spirit),
      patient-centered complementary and integrative medicine (CIM) therapies that
      acknowledge the patients' roles in their own healing processes have the potential
      to provide more efficient and comprehensive chronic pain management. Active self
      care CIM (ACT-CIM) therapies allow for a more diverse, patient-centered treatment
      of complex symptoms, promote self-management, and are relatively safe and cost
      effective. To date, there are no systematic reviews examining the full range of
      ACT-CIM used for chronic pain symptom management. METHODS: A systematic review
      was conducted, using Samueli Institute's Rapid Evidence Assessment of the
      Literature methodology, to rigorously assess both the quality of the research on
      ACT-CIM modalities and the evidence for their efficacy and effectiveness in
      treating chronic pain symptoms. A working group of subject matter experts was
      also convened to evaluate the overall literature pool and develop recommendations
      for the use and implementation of these modalities. RESULTS: Following key
      database searches, 146 randomized controlled trials were included in the review,
      18 of which directly compared ACT-CIM approaches with one another. CONCLUSIONS:
      This article summarizes the current evidence, quality, effectiveness, and safety
      of these modalities. Recommendations and next steps to move this field of
      research forward are also discussed. The entire scope of the review is detailed
      throughout the current Pain Medicine supplement.

PMID- 24734865
TI  - Assessing the quality, efficacy, and effectiveness of the current evidence base
      of active self-care complementary and integrative medicine therapies for the
      management of chronic pain: a rapid evidence assessment of the literature.
AB  - OBJECTIVES: Chronic pain management typically consists of prescription
      medications or provider-based, behavioral, or interventional procedures that are
      often ineffective, may be costly, and can be associated with undesirable side
      effects. Because chronic pain affects the whole person (body, mind, and spirit),
      patient-centered complementary and integrative medicine (CIM) therapies that
      acknowledge the patients' roles in their own healing processes have the potential
      to provide more efficient and comprehensive chronic pain management. Active self
      care CIM (ACT-CIM) therapies allow for a more diverse, patient-centered treatment
      of complex symptoms, promote self-management, and are relatively safe and cost
      effective. To date, there are no systematic reviews examining the full range of
      ACT-CIM used for chronic pain symptom management. METHODS: A systematic review
      was conducted, using Samueli Institute's Rapid Evidence Assessment of the
      Literature methodology, to rigorously assess both the quality of the research on
      ACT-CIM modalities and the evidence for their efficacy and effectiveness in
      treating chronic pain symptoms. A working group of subject matter experts was
      also convened to evaluate the overall literature pool and develop recommendations
      for the use and implementation of these modalities. RESULTS: Following key
      database searches, 146 randomized controlled trials were included in the review.
      CONCLUSIONS: This article provides an introduction and background to the review,
      summarizes the methodological processes involved, details the initial results,
      and identifies strengths and weakness of the review. Specific results of the
      review as well as overall recommendations for moving this field of research
      forward are detailed throughout the current Pain Medicine supplement.

PMID- 24734866
TI  - An analysis of the various chronic pain conditions captured in a systematic
      review of active self-care complementary and integrative medicine therapies for
      the management of chronic pain symptoms.
AB  - OBJECTIVES: Chronic pain management typically consists of prescription
      medications or provider-based, behavioral, or interventional procedures that are
      often ineffective, may be costly, and can be associated with undesirable side
      effects. Because chronic pain affects the whole person (body, mind, and spirit),
      patient-centered complementary and integrative medicine (CIM) therapies that
      acknowledge the patients' roles in their own healing processes have the potential
      to provide more efficient and comprehensive chronic pain management. Active self
      care CIM therapies (ACT-CIM) allow for a more diverse, patient-centered treatment
      of complex symptoms, promote self-management, and are relatively safe and cost
      effective. To date, there are no systematic reviews examining the full range of
      ACT-CIM used for chronic pain symptom management. METHODS: A systematic review
      was conducted, using Samueli Institute's rapid evidence assessment of the
      literature (REAL(c)) methodology, to rigorously assess both the quality of the
      research on ACT-CIM modalities and the evidence for their efficacy and
      effectiveness in treating chronic pain symptoms. A working group of subject
      matter experts was also convened to evaluate the overall literature pool and
      develop recommendations for the use and implementation of these modalities.
      RESULTS: Following key database searches, 146 randomized controlled trials,
      covering 33 different pain conditions, were included in the review. CONCLUSIONS:
      This article categorized studies by pain condition, describing the diagnostic
      criteria used and modalities that seem most effective for each condition.
      Complexities associated with investigating chronic pain populations are also
      discussed. The entire scope of the review, categorized by modality rather than
      pain condition, is detailed throughout the current Pain Medicine supplement.

PMID- 24734867
TI  - Future considerations for dendritic cell immunotherapy against chronic viral
      infections.
AB  - Dendritic cells (DCs) are multifunctional cells that are pivotal in immune
      defense. As such they have been explored as vaccine carriers, largely in cancer
      immunotherapy and against some infectious diseases including HIV and viral
      hepatitis. However, while the use of DCs as vaccine carrier has shown some
      promise in cancer immunotherapy, this approach is laborious and is subject to
      strict quality control, which makes it expensive. Furthermore, in some
      individuals chronically infected with HIV, HCV and/or HBV the numbers of
      circulating DCs are reduced and/or their functions impaired. In vivo expansion
      and mobilization of DCs with Flt3L in combination with antigen and/or adjuvant
      targeting to critical DC receptors may be a more effective approach to control
      viral replication in chronically infected HIV, HBV and/or HCV patients than
      current DC immunotherapy approaches.

PMID- 24734868
TI  - Systematic review on cashew nut allergy.
AB  - Recent studies on cashew nut allergy suggest that the prevalence of cashew nut
      allergy is increasing. Cashew nut consumption by allergic patients can cause
      severe reactions, including anaphylaxis. This review summarizes current knowledge
      on cashew nut allergy to facilitate timely clinical recognition and to promote
      awareness of this emerging food allergy amongst clinicians. The goal of this
      study is to present a systematic review focused on the clinical aspects of
      allergy to cashew nut including the characteristics of cashew nut, the
      prevalence, allergenic components, cross-reactivity, diagnosis and management of
      cashew nut allergy. The literature search yielded 255 articles of which 40 met
      our selection criteria and were considered to be relevant for this review. The 40
      articles included one prospective study, six retrospective studies and seven case
      reports. The remaining 26 papers were not directly related to cashew nut allergy.
      The literature suggests that the prevalence of cashew nut allergy is increasing,
      although the level of evidence for this is low. A minimal amount of cashew nut
      allergen may cause a severe allergic reaction, suggesting high potency comparable
      with other tree nuts and peanuts. Cashew allergy is clearly an underestimated
      important healthcare problem, especially in children.

PMID- 24734869
TI  - The utility of fasting plasma glucose to identify impaired glucose metabolism in
      women with polycystic ovary syndrome.
AB  - We evaluated the utility of impaired fasting plasma glucose as defined by ADA to
      identify women with polycystic ovary syndrome (PCOS) affected by impaired glucose
      metabolism (i.e. impaired fasting glucose, impaired glucose tolerance and
      diabetes mellitus). In 330 women with PCOS, according to ESHRE criteria, an oral
      glucose tolerance test was done. Impaired fasting glucose was present in 36 women
      (12%), impaired glucose tolerance in 29 women (8.8%) and diabetes mellitus in 10
      women (3%), 4 of them have fasting glucose higher than 7 mmol/l. The combination
      of impaired fasting glucose and impaired glucose tolerance was seen in 5 women
      (1.5%). The sensitivity of impaired fasting glucose for the detection of impaired
      glucose tolerance was 24% and specificity 91.8%. When fasting glucose above 5.6
      mmol/l was used as the screening criterion, 28/35 subjects (80%) would have been
      missed. We conclude that fasting plasma glucose is not sufficiently sensitive for
      the detection of impaired glucose tolerance and diabetes mellitus type 2 in women
      with PCOS.

PMID- 24734870
TI  - Live birth following vitrification of in vitro matured oocytes derived from
      sibling smaller follicles at follicle selection phase in the context of in vitro
      fertilization.
AB  - In ovarian stimulation, a 31-year-old woman with polycystic ovary syndrome was at
      the risk of developing ovarian hyperstimulation syndrome, follicle aspiration was
      performed, and eight immature oocytes were collected from follicle fluids. After
      28 h in vitro culture, six of them reached MII and were vitrified. The patient
      failed to conceive in her fresh in vitro fertilization cycle and next two
      replacement cycles. In the third replacement cycle, a successful pregnancy was
      obtained by vitrified-thawed oocytes. This case demonstrates that follicular
      aspiration during follicle selection phase has protective effects against
      developing ovarian hyperstimulation syndrome, and rescued immature oocytes are
      viable and could produce promising embryos for live birth.

PMID- 24734871
TI  - Specific detection and simultaneously localized photothermal treatment of cancer
      cells using layer-by-layer assembled multifunctional nanoparticles.
AB  - There is a great need to develop multifunctional nanoparticles (MFNPs) for cancer
      biomarker-based detection and highly selective therapeutic treatment
      simultaneously. Here we describe a facile approach of layer-by-layer-assembled
      MFNPs conjugated with monoclonal antibody anti-HER2, demonstrating the specific
      detection of breast cancer BT474 cells (biomarker HER2 positive) with a high
      signal-to-noise ratio. The MFNPs contain a well-defined core-shell structure of
      UCNP@Fe3O4@Au coated by poly(ethylene glycol) (PEG) and anti-HER2 antibody,
      displaying excellent dispersity in various aqueous solutions. This unique
      combination of nanoparticles and ligand molecules allows us to perform
      photothermal treatment (PTT) of the cancer cells, while simultaneously
      quantifying the distribution of MFNPs on a cancer cell surface induced by antigen
      antibody binding events. An important finding is that cancer cells adjacent to
      each other or in physical proximity within micrometers may end up with different
      fates of survival or death in PTT. This dramatic difference is determined by the
      antigen-antibody binding events at the interface of MFNPs and cells because of
      tumor cell heterogeneity. Therefore, our experiments reveal a new scale of the
      highly localized feature of the photothermal effect at the single-cell level
      illuminated by a continuous-wave near-IR laser. 

PMID- 24734872
TI  - High-throughput sequencing of Bacillus anthracis in France: investigating genome
      diversity and population structure using whole-genome SNP discovery.
AB  - BACKGROUND: Single nucleotide polymorphisms (SNPs) are ideal signatures for
      subtyping monomorphic pathogens such as Bacillus anthracis. Here we report the
      use of next-generation sequencing technology to investigate the historical,
      geographic and genetic diversity of Bacillus anthracis in France. 122 strains
      isolated over a 60-years period throughout the country were whole-genome
      sequenced and comparative analyses were carried out with a focus on SNPs
      discovery to discriminate regional sub-groups of strains. RESULTS: A total of
      1581 chromosomal SNPs precisely establish the phylogenetic relationships existing
      between the French strains. Phylogeography patterns within the three canSNP sub
      lineages present in France (i.e. B.Br.CNEVA, A.Br.011/009 and A.Br.001/002) were
      observed. One of the more remarkable findings was the identification of a variety
      of genotypes within the A.Br.011/009 sub-group that are persisting in the
      different regions of France. The 560 SNPs defining the A.Br.011/009- affiliated
      French strains split the Trans-Eurasian sub-group into six distinct branches
      without any intermediate nodes. Distinct sub-branches, with some geographic
      clustering, were resolved. The 345 SNPs defining the major B.Br CNEVA sub-lineage
      clustered three main phylogeographic clades, the Alps, the Pyrenees, and the
      Massif Central, with a small Saone-et-Loire sub-cluster nested within the latter
      group. The French strains affiliated to the minor A.Br.001/002 group were
      characterized by 226 SNPs. All recent isolates collected from the Doubs
      department were closely related. Identification of SNPs from whole-genome
      sequences facilitates high-resolution strain tracking and provides the level of
      discrimination required for outbreak investigations. Eight diagnostic SNPs,
      representative of the main French-specific phylogeographic clusters, were
      therefore selected and developed into high-resolution melting SNP discriminative
      assays. CONCLUSIONS: This work has established one of the most accurate
      phylogenetic reconstruction of B. anthracis population structure in a country. An
      extensive next-generation sequencing (NGS) dataset of 122 French strains have
      been created that allowed the identification of novel diagnostic SNPs useful to
      rapidly determine the geographic origin of any strain found in France.

PMID- 24734874
TI  - Measuring physical properties of neuronal and glial cells with resonant
      microsensors.
AB  - Microelectromechanical systems (MEMS) resonant sensors provide a high degree of
      accuracy for measuring the physical properties of chemical and biological
      samples. These sensors enable the investigation of cellular mass and growth,
      though previous sensor designs have been limited to the study of homogeneous cell
      populations. Population heterogeneity, as is generally encountered in primary
      cultures, reduces measurement yield and limits the efficacy of sensor mass
      measurements. This paper presents a MEMS resonant pedestal sensor array
      fabricated over through-wafer pores compatible with vertical flow fields to
      increase measurement versatility (e.g., fluidic manipulation and throughput) and
      allow for the measurement of heterogeneous cell populations. Overall, the
      improved sensor increases capture by 100% at a flow rate of 2 MUL/min, as
      characterized through microbead experiments, while maintaining measurement
      accuracy. Cell mass measurements of primary mouse hippocampal neurons in vitro,
      in the range of 0.1-0.9 ng, demonstrate the ability to investigate neuronal mass
      and changes in mass over time. Using an independent measurement of cell volume,
      we find cell density to be approximately 1.15 g/mL. 

PMID- 24734873
TI  - Identification and characterization of microRNAs in the flag leaf and developing
      seed of wheat (Triticum aestivum L.).
AB  - BACKGROUND: MicroRNAs (miRNAs) regulate various biological processes in plants.
      Considerable data are available on miRNAs involved in the development of rice,
      maize and barley. In contrast, little is known about miRNAs and their functions
      in the development of wheat. In this study, five small RNA (sRNA) libraries from
      wheat seedlings, flag leaves, and developing seeds were developed and sequenced
      to identify miRNAs and understand their functions in wheat development. RESULTS:
      Twenty-four known miRNAs belonging to 15 miRNA families were identified from 18
      MIRNA loci in wheat in the present study, including 15 miRNAs (9 MIRNA loci)
      first identified in wheat, 13 miRNA families (16 MIRNA loci) being highly
      conserved and 2 (2 MIRNA loci) moderately conserved. In addition, fifty-five
      novel miRNAs were also identified. The potential target genes for 15 known miRNAs
      and 37 novel miRNAs were predicted using strict criteria, and these target genes
      are involved in a wide range of biological functions. Four of the 15 known miRNA
      families and 22 of the 55 novel miRNAs were preferentially expressed in the
      developing seeds with logarithm (log2) of the fold change of 1.0 ~ 7.6, and half
      of them were seed-specific, suggesting that they participate in regulating wheat
      seed development and metabolism. From 5 days post-anthesis to 20 days post
      anthesis, miR164 and miR160 increased in abundance in the developing seeds,
      whereas miR169 decreased, suggesting their coordinating functions in the
      different developmental stages of wheat seed. Moreover, 8 known miRNA families
      and 28 novel miRNAs exhibited tissue-biased expression in wheat flag leaves, with
      the logarithm of the fold changes of 0.1 ~ 5.2. The putative targets of these
      tissue-preferential miRNAs were involved in various metabolism and biological
      processes, suggesting complexity of the regulatory networks in different tissues.
      Our data also suggested that wheat flag leaves have more complicated regulatory
      networks of miRNAs than developing seeds. CONCLUSIONS: Our work identified and
      characterised wheat miRNAs, their targets and expression patterns. This study is
      the first to elucidate the regulatory networks of miRNAs involved in wheat flag
      leaves and developing seeds, and provided a foundation for future studies on
      specific functions of these miRNAs.

PMID- 24734875
TI  - Adult fat content: reinterpreting and modelling the Benn Index and related sex
      differences.
AB  - BACKGROUND: In women, the height exponent, p, of the Benn Index, (body
      mass)/height(p), is typically lower than in men, body masses are more weakly
      correlated with height and fat masses tend to be higher. In both sexes fat masses
      correlate only weakly with height. Changes in fat mass are typically accompanied
      by changes in fat-free mass. AIMS: To integrate these facts, together with other
      published findings relating to fat content and to explain why p is lower in
      women. METHODS: Data and statistics are taken from the literature. The
      differences in p are explored by Monte Carlo and algebraic modelling. Mean
      transverse areas of the body (MTAs), calculated as (body mass)/height, are
      related to height. RESULTS AND CONCLUSIONS: The body can be modelled as
      consisting of a component, M1, varying roughly with the cube of height and
      another, M2, varying little with height. The low correlation between total body
      mass and height is due both to M2 and to data scatter. The low p values in women
      relate especially to M2. Relationships amongst height, fatness, MTAs and girths
      of body parts generally conform to this interpretation. Questions are raised as
      to how health risks are best related to fat mass.

PMID- 24734876
TI  - Interocular symmetry analysis of bilateral eyes.
AB  - The purpose of this study was to evaluate the interocular symmetry of several
      biometric parameters between both eyes. The symmetry between the right and left
      eye of 397 subjects in 14 biometric parameters, spherical equivalent of
      refractive error (SE), Jackson crossed cylinder power of refractive error
      astigmatism with axes at 90 degrees  and 180 degrees  (RJ0) and at 45 degrees 
      and 135 degrees  (RJ45), best-corrected visual acuity (BCVA), average corneal
      curvature (CC), Jackson crossed cylinder power of corneal astigmatism (CJ0 and
      CJ45), corneal asphericity coefficient (Q), intraocular pressure (IOP), central
      corneal thickness (CCT), axial length (AL), anterior chamber depth (ACD), lens
      thickness (LT) and vitreous chamber depth (VCD), was assessed by comparative data
      analysis. Aside from RJ0 (p = 0.00), RJ45 (p = 0.02) and Q (p = 0.00), the
      overall interocular differences of other biometric parameters between fellow eyes
      were not significant (p > 0.05). The interocular correlation and Bland-Altman
      plots showed a good agreement between fellow eyes in 14 biometric parameters.
      Correlations between interocular differences in SE and that in RJ0 (p = 0.03), CC
      (p = 0.00), AL (p = 0.00) and VCD (p = 0.00) were statistically significant.
      There were similar strong linear relationships between refractive error
      astigmatism vectors and corneal astigmatism vectors in bilateral eyes. There were
      negative correlations of RJ45 and CJ45 between bilateral eyes. A potentially
      clinically important interocular symmetry in SE, BCVA, CC, CJ0, CJ45, IOP, CCT,
      AL, ACD, LT and VCD is found in this research, while the differences of RJ0, RJ45
      and Q between left and right eyes seem a bit large. The negative interocular
      relationships of RJ45 and CJ45 demonstrate moderate mirror symmetry exists among
      fellow eyes. High interocular symmetry in bilateral eyes may be helpful in
      intraocular lens power calculation, intraocular pressure evaluation, post
      operative visual acuity and refraction prediction at the time the fellow eye is
      undergoing refractive surgery.

PMID- 24734877
TI  - Multifunctional graphene optical modulator and photodetector integrated on
      silicon waveguides.
AB  - Graphene's unique optoelectronic properties have been exploited for many photonic
      applications. Here, we demonstrate a single graphene-based device that
      simultaneously provides efficient optical modulation and photodetection. The
      graphene device is integrated on a silicon waveguide and is tunable with a
      graphene gate to achieve a near-infrared photodetection responsivity of 57 mA/W
      and modulation depth of 64% with GHz bandwidth. Simultaneous modulation of
      photocurrent and optical transmission has been achieved, which may lead to
      unprecedented optoelectronic applications. 

PMID- 24734879
TI  - Transient electrostatic interactions dominate the conformational equilibrium
      sampled by multidomain splicing factor U2AF65: a combined NMR and SAXS study.
AB  - Multidomain proteins containing intrinsically disordered linkers exhibit large
      scale dynamic modes that play key roles in a multitude of molecular recognition
      and signaling processes. Here, we determine the conformational space sampled by
      the multidomain splicing factor U2AF65 using complementary nuclear magnetic
      resonance spectroscopy and small-angle scattering data. Available degrees of
      conformational freedom are initially stochastically sampled and experimental data
      then used to delineate the potential energy landscape in terms of statistical
      probability. The spatial distribution of U2AF65 conformations is found to be
      highly anisotropic, comprising significantly populated interdomain contacts that
      appear to be electrostatic in origin. This hypothesis is supported by the
      reduction of signature PREs reporting on expected interfaces with increasing salt
      concentration. The described spatial distribution reveals the complete spectrum
      of the unbound forms of U2AF65 that coexist with the small percentage of a
      preformed RNA-bound domain arrangement required for polypyrimidine-tract
      recognition by conformational selection. More generally, the proposed approach to
      describing conformational equilibria of multidomain proteins can be further
      combined with other experimental data that are sensitive to domain dynamics. 

PMID- 24734880
TI  - Role of the surface chemistry of ceria surfaces on silicate adsorption.
AB  - Ceria nanoparticles (NPs) have been widely explored as a promising material in
      various fields. As synthesized under various physicochemical conditions, it
      exhibits the different surface chemistry. Here, the role of hydroxyl and nitrate
      group on ceria surface, formed under various physicochemical conditions, for the
      silicate adsorption was experimentally and theoretically investigated based on
      the adsorption isotherms and theoretical analyses using density functional theory
      (DFT) calculation. Experimental results acquired from adsorption isotherms with
      Freundlich model indicated that the nitrate group shows a much higher affinity
      with silicate than the hydroxyl groups. These phenomena were demonstrated through
      the theoretical approaches that exhibit the binding energy of the NO3-ceria (
      4.383 eV) on the SiO2 surface being much higher than that of the OH-ceria (-3.813
      eV). In good agreement with the experimental and the theoretical results based on
      adsorption properties, the results of chemical mechanical planarization (CMP)
      also show that the nitrate groups significantly enhance the removal of SiO2 than
      the hydroxyl groups. The results investigated in this study will provide
      researchers, studying the ceria NPs, with guidelines on the importance of
      exploring the surface chemistry of ceria. 

PMID- 24734881
TI  - Deaths due to traumatic brain injury in Austria between 1980 and 2012.
AB  - BACKGROUND: To investigate changes in TBI mortality in Austria during 1980-2012
      and to identify causes for these changes. METHODS: Statistik Austria provided
      data (from death certificates) on all TBI deaths from January 1980-December 2012.
      Data included year/month of death, age, sex, residency of the cases and mechanism
      of accident. Data regarding the size of the age groups was obtained from
      Statistik Austria. Mortality rates (MR; deaths/10(5) population/year) were
      calculated for male vs. female patients and for different age groups. Changes in
      mechanisms of TBI were evaluated. RESULTS: The MR decreased from 28.1 to 11.8
      deaths/10(5) population/year. Traffic-related TBI deaths decreased from 62% to
      9%. This caused a significant decrease in TBI deaths in younger age groups. Fall
      related TBI deaths (mostly geriatric cases) remained unchanged. Falls became the
      leading cause; its rate increased from 22% to 64% of all TBI deaths. Thus, the
      mean age of fatal TBI cases increased by 20 years and the rate of cases aged <60
      years decreased from 71% to 28%. Another important cause was suicide by firearms;
      its rate increased from 10% to 23% of all TBI deaths. CONCLUSIONS: These findings
      warrant better prevention of falls in the elderly and of suicides.

PMID- 24734882
TI  - Soluble urokinase plasminogen activator receptor, the candidate prophetic
      biomarker in severe inflammatory response syndrome.

PMID- 24734883
TI  - The effect of starvation on plastid number and photosynthetic performance in the
      kleptoplastidic dinoflagellate Amylax triacantha.
AB  - The dinoflagellate Amylax triacantha is known to retain plastids of cryptophyte
      origin by engulfing the mixotrophic ciliate Mesodinium rubrum, itself a consumer
      of cryptophytes. However, there is no information on the fate of the prey's
      organelles and the photosynthetic performance of the newly retained plastids in
      A. triacantha. In this study, we conducted a starvation experiment to observe the
      intracellular organization of the prey's organelles and temporal changes in the
      photosynthetic efficiency of acquired plastids in A. triacantha. The
      ultrastructural observations revealed that while the chloroplast-mitochondria
      complexes and nucleus of cryptophyte were retained by A. triacantha, other
      ciliate organelles were digested in food vacuoles. Acquired plastids were
      retained in A. triacantha for about 1 mo and showed photosynthetic activities for
      about 18 d when measured by a pulse-amplitude modulation fluorometer. 

PMID- 24734884
TI  - The brain in micro- and hypergravity: the effects of changing gravity on the
      brain electrocortical activity.
AB  - Understanding the effects of increased and decreased gravity on central nervous
      system is essential for developing proper physical and cognitive countermeasures
      to assure safe and effective space missions and human survival in space. This
      short review covers the available literature on the brain electrocortical
      activity effects of decreased and increased gravitational force comparing to the
      1g Earth conditions. Among all neuroimaging methods such as functional magnetic
      resonance imaging (fMRI), positron-emission tomography (PET), diffusion tensor
      imaging (DTI), the electroencephalography (EEG) was found to be suitable method
      to monitor brain electrocortical activity in the extreme environments. Due to
      complexity and high cost of space flight missions, ground-based models have been
      employed to simulate microgravity effects on human body. Surprisingly, there is
      very limited number of publications reporting gravity-dependent EEG spectral
      changes. With increased gravity there are initially increased EEG activity in
      higher frequencies and at around 4 g appears loss of consciousness with
      accompanying slowing of EEG due to hypoxia. In microgravity, the most prevalent
      changes in EEG are faster frequencies such as alpha and beta. The results from
      simulated microgravity (bed rest) are pointing to changes in theta and alpha,
      representing signs of cortical inhibition. The changes in EEG activity in space
      flight are attributed to a decreased sensorimotor input while in parabolic
      flights short and fast transitions from hyper to microgravity presumably reflect
      lower arousal levels and emotional processes in microgravity. Thus, based on
      limited research about gravity-related changes in EEG from different environments
      it is difficult to draw any unequivocal conclusions. Additional systematic
      studies about electrocortical activity in space and parabolic flights, as well as
      longer bed rest studies are needed in order to advance knowledge about brain
      functioning in extreme conditions such as space flights.

PMID- 24734885
TI  - Population pharmacodynamic analysis of LDL-cholesterol lowering effects by
      statins and co-medications based on electronic medical records.
AB  - AIMS: HMG-CoA reductase inhibitors are available for use in low density
      lipoprotein-cholesterol (LDL-C) lowering therapy. The purposes of this study were
      to develop a population pharmacodynamic (PPD) model to describe the time course
      for the LDL-C lowering effects of statins and assess the efficacy of combination
      therapy based on electronic medical records. METHODS: Patient backgrounds,
      laboratory tests and prescribed drugs were collected retrospectively from
      electronic medical records. Patients who received atorvastatin, pitavastatin or
      rosuvastatin were enrolled. A physiological indirect response model was used to
      describe the changes observed in LDL-C concentrations. The PPD analysis was
      performed using nonmem 7.2.0 with the first order conditional estimation method
      with interaction (FOCE-INTER). RESULTS: An indirect response Imax model, based on
      the 2863 LDL-C concentrations of 378 patients, successfully and quantitatively
      described the time course for the LDL-C lowering effects of three statins. The
      combination of ezetimibe, a cholesterol absorption inhibitor, decreased the LDL
      synthesis rate (Kin ) by 10.9%. A simulation indicated that the combined
      treatment of ezetimibe with rosuvastatin (2.5 mg day(-1) ) led to superior
      clinical responses than those with high doses of rosuvastatin (5.0 mg day(-1) )
      monotherapy, even in patients with higher baseline LDL-C concentrations prior to
      the treatment. CONCLUSIONS: A newly constructed PPD model supported previous
      evidence for the beneficial effects of ezetimibe combined with rosuvastatin. In
      addition, the established framework is expected to be applicable to other drugs
      without pharmacokinetic data in clinical practice.

PMID- 24734887
TI  - Protective effect of N-acetylcysteine (NAC) on renal ischemia/reperfusion injury
      through Nrf2 signaling pathway.
AB  - The aim of this study was to investigate whether N-acetylcysteine (NAC), a known
      antioxidant, can protect kidney against ischemic injury through regulating Nrf2
      signaling pathway. The expression of Nrf2, HO-1 and cleaved caspase 3 were
      analyzed by Western blot analysis. Apoptosis of renal tubular epithelial cells
      was assessed by the TUNEL method. Malondialdehyde (MDA) levels were measured by
      the thiobarbituric acid reaction. Blood serum creatinine and blood urea nitrogen
      levels were measured with an Olympus automatic multi-analyzer. We found that NAC
      significantly increased Nrf2 and downstream HO-1 expression. Furthermore, NAC
      significantly decreased cleaved caspase 3, p53 and renal epithelial tubular cell
      apoptosis. In addition, NAC reduced the MDA level. These findings suggest that
      the protective action of NAC on ischemia renal injury is associated closely with
      Nrf2 signaling pathway.

PMID- 24734888
TI  - A mouse renin distal enhancer is essential for blood pressure homeostasis in BAC
      rescued renin-null mutant mice.
AB  - Renin is predominantly expressed in juxtaglomerular cells in the kidney and
      regulates blood pressure homeostasis. To examine possible in vivo functions of a
      mouse distal enhancer (mdE), we generated transgenic mice (TgM) carrying either
      wild-type or mdE-deficient renin BACs (bacterial artificial chromosome),
      integrated at the identical chromosomal site. In the kidneys of the TgM, the mdE
      contributed 80% to basal renin promoter activity. To test for possible
      physiological roles for the mdE, renin BAC transgenes were used to rescue the
      hypotensive renin-null mice. Interestingly, renal renin expression in the
      Tg(BAC):renin-null compound mice was indistinguishable between the wild-type and
      mutant BAC carriers. Surprisingly, however, the plasma renin activity and
      angiotensin I concentration in the mdE compound mutant mice were significantly
      lower than the same parameters in the control mice, and the mutants were
      consistently hypotensive, demonstrating that blood pressure homeostasis is
      regulated through transcriptional cis elements controlling renin activity.

PMID- 24734889
TI  - Heterogeneity of cardiovascular risk factors profile in non-diabetic women 2-24
      months post gestational diabetes mellitus.
AB  - Previously gestational diabetic (pGDM) women are characterized by high
      cardiovascular risk (CVR). The aim of this study was to assess the CVR markers
      levels in non-diabetic pGDM women in relation to time postpartum and to soluble E
      selectin (sES) level. We investigated 125 women aged 18-40 years with a history
      of GDM between 2 and 24 months after their pregnancy. We evaluated age, body mass
      index (BMI), waist circumference, glucose levels during the oral glucose
      tolerance test (OGTT), levels of insulin and the parameters of endothelial
      dysfunction, fibrinolysis activity, low-grade systemic inflammation and lipid
      profiles. Prediabetes was identified in 38 women (30%), while in the remaining
      women OGTT results were normal. The tests performed >6 months revealed decreased
      hs-CRP (p = 0.01), sICAM-1 (p = 0.01), and elevated sES (p = 0.01) >12 months
      after adjustment for age, BMI, waist circumference and 2 h OGTT glucose. In the
      subgroup tested <=12 months after an index pregnancy sES was independently
      associated with hs-CRP (p < 0.0001) and triglycerides (p = 0.0139). No
      association was found between sES and remaining parameters in women tested >12
      months postpartum. We conclude that the period 2-24 months post GDM is
      heterogeneous with respect to the CVR markers. The plasma level of hs-CRP could
      be useful as an important cardiovascular risk marker up to 12 months postpartum
      in non-diabetic pGDM women.

PMID- 24734886
TI  - Regulation of B lymphocytes and plasma cells by innate immune mechanisms and
      stromal cells in rheumatoid arthritis.
AB  - B cells mediate multiple functions that influence immune and inflammatory
      responses in rheumatoid arthritis. Production of a diverse array of
      autoantibodies can happen at different stages of the disease, and are important
      markers of disease outcome. In turn, the magnitude and quality of acquired
      humoral immune responses is strongly dependent on signals delivered by innate
      immune cells. Additionally, the milieu of cells and chemokines that constitute a
      niche for plasma cells rely strongly on signals provided by stromal cells at
      different anatomical locations and times. The chronic inflammatory state
      therefore importantly impacts the developing humoral immune response and its
      intensity and specificity. We focus this review on B cell biology and the role of
      the innate immune system in the development of autoimmunity in patients with
      rheumatoid arthritis.

PMID- 24734890
TI  - Immediate loading of post-extractive single-tooth implants: a 1-year prospective
      study.
AB  - PURPOSE: The aim of this prospective clinical trial was to assess clinical,
      radiological, and esthetic outcomes of immediate-loaded post-extractive implants
      after 1 year of follow-up. MATERIALS AND METHODS: Twenty-four consecutive
      patients (15 females and nine males) with a mean age of 47.27 years (range 35-65)
      requiring single-tooth extraction in the maxillary or mandibular anterior or
      premolar areas were enrolled. Twenty-five NobelActive implants (Nobel Biocare,
      Goteborg, Sweden) were placed and loaded immediately after tooth extraction. The
      definitive prosthetic restoration was delivered 6 months later. Clinical
      parameters, marginal bone loss, as well as, pink and white esthetic scores (PES
      and WES) were evaluated at 3, 6, and 12 months after implant placement. RESULTS:
      After 12-month follow-up period, a success rate of 91.67% was reported: Two of
      the 25 initially placed implants were lost after 4 weeks due to lack of
      osseointegration. The mean marginal bone loss after 1-year follow-up was 0.383
      (SD +/- 0.749) at mesial site and 0.278 (SD +/- 0.595) at distal site. No
      statistically significant changes in the full-mouth plaque score (FMPS) and in
      the full-mouth bleeding score (FMBS) were observed from baseline to 12 months.
      The mean total PES/WES was 17.13 +/- 1.91 (range: 13-20). None of 23 implants had
      an overall score <12 (threshold of clinical acceptability). CONCLUSION: Within
      the limitations of the present study, when careful patient selection and strict
      clinical protocol are observed, the immediate placement and loading of a single
      NobelActive(TM) implant in a fresh extraction socket may be considered a valuable
      and predictable option in terms of implant success as well as hard and soft
      tissues stability.

PMID- 24734892
TI  - Gelling properties of chia seed and flour.
AB  - Healthy oil profile of chia has been well established. Chia could also be a good
      source of gel. The characteristics of chia gel were studied and compared to guar
      gum and gelatin which are commonly used in the food industry. The properties
      tested were water and oil holding capacities, viscosity, line-spread;
      emulsification activity and freeze-thaw stability. The extracted chia gels from
      seeds and flour were analyzed for moisture, ash, protein, crude fiber, oil, and
      fatty acid profile. Water-holding capacity, oil-holding capacity, viscosity,
      emulsion activity, and freeze-thaw stability of the extracted chia seed gel were
      similar to guar gum, and gelatin. Chia gel is a polysaccharide based gel mainly
      consists of crude fiber (58%) and carbohydrate (34%). Extracted chia seed gel has
      a great potential in food formulations as thickening agent, emulsifying agent,
      and as a stabilizer. PRACTICAL APPLICATION: Extracted chia seed gel has good
      water-holding capacity, oil-holding capacity, viscosity, emulsion activity, and
      freeze-thaw ability. Chia seed gel has potential application in food formulation
      as a thickening agent, emulsifying agent, and as a stabilizer in frozen food
      product.

PMID- 24734891
TI  - Glycemic control after 6 days of insulin pump reservoir use in type 1 diabetes:
      results of double-blind and open-label cross-over trials of insulin lispro and
      insulin aspart.
AB  - BACKGROUND: The objective of the current study was to assess mean self-monitored
      blood glucose (SMBG), on day 6 of 6 days of continuous reservoir wear (6D), with
      insulin lispro (Lis) or insulin aspart (Asp). METHODS: Two 24-week, randomized
      trials were conducted in subjects with type 1 diabetes treated by continuous
      subcutaneous insulin infusion (CSII) for >=6 months, with a mean total daily
      insulin dose capable of supporting 6 days of in-reservoir use. Study 1 had an
      open-label, six-sequence, three-treatment, three-period, cross-over design. Study
      2 had a double-blind, two-sequence, two-treatment, two-period, cross-over design.
      The primary efficacy measure was the mean of Day 6, seven-point SMBG profiles for
      insulin lispro 6D (Lis6D) and insulin aspart 6D (Asp6D) treatment periods. Safety
      measures were also assessed. RESULTS: Lis did not achieve noninferiority (SMBG;
      margin = 0.6 mmol/L [10.8 mg/dL]) to Asp on Day 6 of reservoir wear in either
      Study (least-squares mean difference: Study 1 = 0.48 mmol/L [8.64 mg/dL]; 95%
      confidence interval [CI] [0.20, 0.76], Study 2 = 0.36 mmol/L [6.49 mg/dL]; 95% CI
      [0.06, 0.66]). Noninferiority was demonstrated for overall daily mean of SMBG
      values over days 1 to 6 of reservoir use during each treatment period. In the Lis
      treatment period, subjects reported a lower documented and total hypoglycemia
      rate per 30 days and a higher rate of non-explained hyperglycemia than in the Asp
      treatment period. CONCLUSION: While the mean blood glucose on Day 6 of Lis6D did
      not meet non-inferiority, the overall daily mean blood glucose was not different,
      with a decreased rate of hypoglycemia with Lis.

PMID- 24734893
TI  - Serum concentrations of HE4 change little during in vitro fertilization.
AB  - OBJECTIVE: Human epididymal secretory protein 4 (HE4) is a biomarker for ovarian
      cancer. The effect of follicle stimulating hormone (FSH) stimulation during in
      vitro fertilization (IVF) on HE4 was evaluated to determine whether substantial
      hormonal stimulation of the ovaries affects the serum levels of this marker.
      Findings were compared with serum concentrations of cancer antigen 125 (CA125),
      currently the most commonly used marker for ovarian cancer. DESIGN: Prospective
      cohort study. SETTING: University hospital infertility clinic. POPULATION:
      Infertility patients undergoing IVF treatment. METHODS: We determined the serum
      concentration of HE4 and CA125 in serial blood samples in 20 women treated with
      IVF. Samples were taken following gonadotrophin-releasing hormone agonist
      suppression, two to three times during FSH stimulation, at ovum pick-up and 2
      weeks following embryo transfer at the time of the pregnancy test. Ovarian
      follicles were counted and serum estradiol concentrations measured throughout
      treatment. MAIN OUTCOME MEASURES: Serum HE4, CA125 and estradiol concentrations.
      RESULTS: Serum HE4 levels did not increase significantly during the FSH
      stimulation. The majority of values remained below the normal reference range
      (<70 pm) throughout the treatment. Serum CA125 concentration also remained low
      during stimulation. Serum estradiol concentration reflected the severity of
      ovarian stimulation during IVF, increasing 3.9-fold with stimulation.
      CONCLUSIONS: Serum HE4 concentrations respond little if at all to
      supraphysiological ovarian stimulation, suggesting that the amount of circulating
      HE4 in women with normal ovaries is independent of gonadotropin stimulation.
      Hormonal stimulation of the ovaries is unlikely to affect the differential
      diagnosis of ovarian tumors with HE4.

PMID- 24734894
TI  - BisQC: an operational pipeline for multiplexed bisulfite sequencing.
AB  - BACKGROUND: Bisulfite sequencing is the most efficient single nucleotide
      resolution method for analysis of methylation status at whole genome scale, but
      improved quality control metrics are needed to better standardize experiments.
      RESULTS: We describe BisQC, a step-by-step method for multiplexed bisulfite
      converted DNA library construction, pooling, spike-in content, and
      bioinformatics. We demonstrate technical improvements for library preparation and
      bioinformatic analyses that can be done in standard laboratories. We find that
      decoupling amplification of bisulfite converted (bis) DNA from the indexing
      reaction is an advantage, specifically in reducing total PCR cycle number and pre
      selecting high quality bis-libraries. We also introduce a progressive PCR method
      for optimal library amplification and size-selection. At the sequencing stage, we
      thoroughly test the benefits of pooling non-bis DNA library with bis-libraries
      and find that BisSeq libraries can be pooled with a high proportion of non-bis
      DNA libraries with minimal impact on BisSeq output. For informatics analysis, we
      propose a series of optimization steps including the utilization of the
      mitochondrial genome as a QC standard, and we assess the validity of using
      duplicate reads for coverage statistics. CONCLUSION: We demonstrate several
      quality control checkpoints at the library preparation, pre-sequencing, post
      sequencing, and post-alignment stages, which should prove useful in determining
      sample and processing quality. We also determine that including a significant
      portion of non-bisulfite converted DNA with bisulfite converted DNA has a minimal
      impact on usable bisulfite read output.

PMID- 24734895
TI  - Why the body comes first: effects of experimenter touch on infants' word finding.
AB  - The lexicon of 6-month-olds is comprised of names and body part words. Unlike
      names, body part words do not often occur in isolation in the input. This
      presents a puzzle: How have infants been able to pull out these words from the
      continuous stream of speech at such a young age? We hypothesize that caregivers'
      interactions directed at and on the infant's body may be at the root of their
      early acquisition of body part words. An artificial language segmentation study
      shows that experimenter-provided synchronous tactile cues help 4-month-olds to
      find words in continuous speech. A follow-up study suggests that this
      facilitation cannot be reduced to the highly social situation in which the
      directed interaction occurs. Taken together, these studies suggest that direct
      caregiver-infant interaction, exemplified in this study by touch cues, may play a
      key role in infants' ability to find word boundaries, and suggests that early
      vocabulary items may consist of words often linked with caregiver touches. A
      video abstract of this article can be viewed at http://youtu.be/NfCj5ipatyE. 

PMID- 24734896
TI  - Using findings from observational studies to guide vitamin D randomized
      controlled trials.

PMID- 24734897
TI  - Oxygen-vacancy-induced polar behavior in (LaFeO3)2/(SrFeO3) superlattices.
AB  - Complex oxides displaying ferroelectric and/or multiferroic behavior are of high
      fundamental and applied interest. In this work, we show that it is possible to
      achieve polar order in a superlattice made up of two nonpolar oxides by means of
      oxygen vacancy ordering. Using scanning transmission electron microscopy imaging,
      we show the polar displacement of magnetic Fe ions in a superlattice of
      (LaFeO3)2/(SrFeO3) grown on a SrTiO3 substrate. Using density functional theory
      calculations, we systematically study the effect of epitaxial strain, octahedral
      rotations, and surface terminations in the superlattice and find them to have a
      negligible effect on the antipolar displacements of the Fe ions lying in between
      SrO and LaO layers of the superlattice (i.e., within La0.5Sr0.5FeO3 unit cells).
      The introduction of oxygen vacancies, on the other hand, triggers a polar
      displacement of the Fe ions. We confirm this important result using electron
      energy loss spectroscopy, which shows partial oxygen vacancy ordering in the
      region where polar displacements are observed and an absence of vacancy ordering
      outside of that area. 

PMID- 24734898
TI  - Maternal and perinatal outcomes in women with placenta praevia and accreta in
      teaching hospitals in Western Turkey.
AB  - In this retrospective study, we investigated patient characteristics and fetal
      and maternal outcomes of placenta praevia and accreta at two tertiary hospitals
      in Istanbul. A total of 364 pregnancies complicated by placenta praevia with (n =
      46) and without (n = 318) placenta accreta managed between January 2005 and
      December 2010 were reviewed. Among 364 women, 46 (12.6%) had placenta accreta and
      318 (87.4%) had placenta praevia without accreta. The rates of curettage history
      and caesarean delivery were significantly higher in the group with placenta
      accreta. Furthermore, we found that emergency surgery had negative effects on
      maternal outcomes in the placenta praevia group. In addition, when accreta was
      suspected at ultrasound examination in women who had placenta praevia, the mean
      estimated blood loss during surgery was reduced significantly. If placenta
      praevia is detected, a careful ultrasound examination should be performed and the
      patient should undergo elective surgery at a tertiary referral hospital.

PMID- 24734899
TI  - Enhanced charge transfer by gold nanoparticle at DNA modified electrode and its
      application to label-free DNA detection.
AB  - Rational utilization of nanomaterials to construct electrochemical nucleic acid
      sensors has attracted large attention in recent years. In this work, we
      systematically interrogate the interaction between gold nanoparticles (GNPs) and
      single-strand DNA (ssDNA) immobilized on an electrode surface and then take
      advantage of the ultrahigh charge-transfer efficiency of GNPs to develop a novel
      DNA sensing method. Specifically, ssDNA modified gold electrode can adsorb GNPs
      because of the interaction between gold and nitrogen-containing bases; thus, the
      negative electrochemical species [Fe(CN)6](3-/4-) may transfer electrons to
      electrode through adsorbed GNPs. In the presence of target DNA, the formed double
      strand DNA (dsDNA) cannot capture GNPs onto the electrode surface and the dsDNA
      may result in a large charge-transfer resistance owing to the negatively charged
      phosphate backbones of DNA. So a simple but sensitive method for the detection of
      target DNA can be developed by using GNPs without any requirement of
      modification. Experimental results demonstrate that the electrochemical method we
      have proposed in this work can detect as low as 1 pM breast cancer gene BRCA1 in
      a 10 MUL sample volume without any signal amplification process or the
      involvement of other synthesized complex, which may provide an alternative for
      cancer DNA detection. This method may also be generalized for detecting a
      spectrum of targets using functional DNA (aptamer, metal-specific
      oligonucleotide, or DNAzyme) in the future. 

PMID- 24734900
TI  - Quantitative chemical imaging of the intracellular spatial distribution of
      fundamental elements and light metals in single cells.
AB  - We report a method that allows a complete quantitative characterization of whole
      single cells, assessing the total amount of carbon, nitrogen, oxygen, sodium, and
      magnesium and providing submicrometer maps of element molar concentration, cell
      density, mass, and volume. This approach allows quantifying elements down to
      10(6) atoms/MUm(3). This result was obtained by applying a multimodal fusion
      approach that combines synchrotron radiation microscopy techniques with off-line
      atomic force microscopy. The method proposed permits us to find the element
      concentration in addition to the mass fraction and provides a deeper and more
      complete knowledge of cell composition. We performed measurements on LoVo human
      colon cancer cells sensitive (LoVo-S) and resistant (LoVo-R) to doxorubicin. The
      comparison of LoVo-S and LoVo-R revealed different patterns in the maps of Mg
      concentration with higher values within the nucleus in LoVo-R and in the
      perinuclear region in LoVo-S cells. This feature was not so evident for the other
      elements, suggesting that Mg compartmentalization could be a significant trait of
      the drug-resistant cells. 

PMID- 24734902
TI  - Maximal intended velocity training induces greater gains in bench press
      performance than deliberately slower half-velocity training.
AB  - The purpose of this study was to compare the effect on strength gains of two
      isoinertial resistance training (RT) programmes that only differed in actual
      concentric velocity: maximal (MaxV) vs. half-maximal (HalfV) velocity. Twenty
      participants were assigned to a MaxV (n = 9) or HalfV (n = 11) group and trained
      3 times per week during 6 weeks using the bench press (BP). Repetition velocity
      was controlled using a linear velocity transducer. A complementary study (n = 10)
      aimed to analyse whether the acute metabolic (blood lactate and ammonia) and
      mechanical response (velocity loss) was different between the MaxV and HalfV
      protocols used. Both groups improved strength performance from pre- to post
      training, but MaxV resulted in significantly greater gains than HalfV in all
      variables analysed: one-repetition maximum (1RM) strength (18.2 vs. 9.7%),
      velocity developed against all (20.8 vs. 10.0%), light (11.5 vs. 4.5%) and heavy
      (36.2 vs. 17.3%) loads common to pre- and post-tests. Light and heavy loads were
      identified with those moved faster or slower than 0.80 m . s(-1) (~ 60% 1RM in
      BP). Lactate tended to be significantly higher for MaxV vs. HalfV, with no
      differences observed for ammonia which was within resting values. Both groups
      obtained the greatest improvements at the training velocities (<= 0.80 m . s(
      1)). Movement velocity can be considered a fundamental component of RT intensity,
      since, for a given %1RM, the velocity at which loads are lifted largely
      determines the resulting training effect. BP strength gains can be maximised when
      repetitions are performed at maximal intended velocity.

PMID- 24734903
TI  - Microbial communities associated with tree bark foliose lichens: a perspective on
      their microecology.
AB  - Tree-bark, foliose lichens occur widely on a global scale. In some locales, such
      as forests, they contribute a substantial amount of biomass. However, there are
      few research reports on microbial communities including eukaryotic microbes
      associated with foliose lichens. Lichens collected from tree bark at 11 locations
      (Florida, New York State, Germany, Australia, and the Arctic) were examined to
      determine the density and C-biomass of bacteria and some eukaryotic microbes,
      i.e. heterotrophic nanoflagellates (HNF) and amoeboid protists. A rich microbial
      diversity was found, including large plasmodial slime molds, in some cases
      exceeding 100 MUm in size. The densities of HNF and amoeboid protists were each
      positively correlated with densities of bacteria, r = 0.84 and 0.80, respectively
      (p < 0.01, N = 11 for each analysis) indicating a likely bacterial-based food
      web. Microbial densities (number/g lichen dry weight) varied markedly across the
      geographic sampling sites: bacteria (0.7-13.1 * 10(8) ), HNF (0.2-6.8 * 10(6) )
      and amoeboid protists (0.4-4.6 * 10(3) ). The ranges in C-biomass (MUg/g lichen
      dry weight) across the 11 sites were: bacteria (8.8-158.5), HNF (0.03-0.85), and
      amoeboid protists (0.08-540), the latter broad range was due particularly to
      absence or presence of large slime mold plasmodia. 

PMID- 24734904
TI  - miRNA-155 controls mast cell activation by regulating the PI3Kgamma pathway and
      anaphylaxis in a mouse model.
AB  - BACKGROUND: Mast cells (MCs) play a central role in allergic and inflammatory
      disorders by rapid degranulation and release of inflammatory mediators upon
      antigen-driven engagement of the FcepsilonRI. Receptor-mediated MC responses are
      controlled by the activation of different isoforms of phosphoinositide-3-kinase
      (PI3K) and the downstream signaling processes. Recent evidence suggests that
      miRNAs are important molecular players regulating the PI3K/Akt pathway. METHODS:
      The role of miR-155 in the regulation of MC functions in vivo was studied in the
      passive cutaneous anaphylaxis (PCA) MC-dependent model. WT and miR-155(-/-) mice
      were injected intradermally with anti-DNP-IgE and intravenously with the antigen
      DNP-HSA. Ear swelling was assessed to evaluate the anaphylactic response. All
      investigations, to characterize miR-155 specific activities in MCs, were
      conducted comparing WT and miR-155(-/-) bone marrow-derived MCs (BMMCs). RESULTS:
      We report that miR-155(-/-) mice display enhanced anaphylaxis reactions. Although
      miR-155(-/-) BMMCs show normal development, proliferation, and survival, miR-155
      deficiency enhances FcepsilonRI-mediated degranulation and release of TNF-alpha,
      IL-13, and IL-6. Interestingly, the level of Akt phosphorylation on both of its
      regulatory residues Thr308 and Ser473 was increased in miR-155(-/-) compared to
      WT BMMCs. Gene expression profiling showed that miR-155(-/-) BMMCs exhibited
      significantly increased expression of the adapter PI3Kgamma subunits Pik3r5
      (p101) and Pik3r6 (p84, p87(PIKAP) ). Furthermore, selective blockade of the
      PI3Kgamma pathway inhibited degranulation in miR-155(-/-) BMMCs. CONCLUSIONS:
      Thus, we suggest that miR-155 plays a critical role in FcepsilonRI-mediated MC
      responses by modulating components of the PI3Kgamma pathway. This newly
      identified mechanism of miRNA-controlled MC activation may affect the initiation
      and maintenance of allergic disorders.

PMID- 24734905
TI  - A transition metal-free Minisci reaction: acylation of isoquinolines, quinolines,
      and quinoxaline.
AB  - Transition metal-free acylation of isoquinoline, quinoline, and quinoxaline
      derivatives has been developed employing a cross dehydrogenative coupling (CDC)
      reaction with aldehydes using substoichiometric amount of TBAB
      (tetrabutylammonium bromide, 30 mol %) and K2S2O8 as an oxidant. This
      intermolecular acylation of electron-deficient heteroarenes provides an easy
      access and a novel acylation method of heterocyclic compounds. The application of
      this CDC strategy for acylation strategy has been illustrated in synthesizing
      isoquinoline-derived natural products. 

PMID- 24734906
TI  - The potential of radioimmunotherapy as a new hope for HIV patients.
AB  - HIV/AIDS remains an enormous public health burden. Advances in anti-retroviral
      therapy (ART) have greatly reduced mortality and morbidity but HIV remains
      incurable, with patients suffering numerous disease- and treatment-related side
      effects. Any curative strategy for HIV must selectively eliminate existing
      infected cells. Radioimmunotherapy (RIT) is an established clinical modality in
      cancer treatment and has been shown to be effective in multiple infectious
      diseases models. We have recently demonstrated that RIT using a gp41-targeting
      antibody was effective and safe in eliminating HIV-infected cells in vivo (in
      mice), in vitro, and ex vivo in cells from HIV patients treated with ART. In
      addition, there is strong evidence that this radiolabeled antibody can eliminate
      HIV infected cells across the blood brain barrier. We consider RIT to be the most
      promising backbone strategy for HIV eradication.

PMID- 24734907
TI  - Differentially expressed miRNAs in cancer-stem-like cells: markers for tumor cell
      aggressiveness of pancreatic cancer.
AB  - Pancreatic cancer (PC) is one of the most deadly cancers. The higher mortality is
      in part due to treatment resistance and early onset of metastasis. The existence
      of cancer-stem-like cells (CSLCs) has been widely accepted to be responsible for
      tumor aggressiveness in PC. Emerging evidence suggests that CSLCs have the
      capacity for increased cell growth, cell migration/invasion, metastasis, and
      treatment resistance, which leads to poor clinical outcome. However, the
      molecular role of CSLCs in tumor development and progression is poorly
      understood. Therefore, mechanistic understanding, and targeted killing of CSLCs
      may provide a newer therapeutic strategy for the treatment of PC. It has been
      well accepted that microRNAs (miRNAs) play critical roles during tumor
      development and progression through deregulation of multiple genes. Moreover,
      deregulated expression of miRNAs may also play a key role in the regulation of
      CSLC characteristics and functions. Here we show that isolated
      CD44(+)/CD133(+)/EpCAM(+) cells (triple-marker-positive cells) from human PC cell
      lines, MiaPaCa-2 and L3.6pl cells, display aggressive characteristics, such as
      increased cell growth, clonogenicity, cell migration, and self-renewal capacity,
      which is consistent with overexpression of CSLC signatures/markers. We also found
      deregulated expression of over 400 miRNAs, including let-7, miR-30, miR-125b, and
      miR-335, in CSLCs. As a proof-of-concept, knockdown of miR-125b resulted in the
      inhibition of tumor cell aggressiveness of CSLCs (triple-marker-positive cells),
      consistent with the downregulation of CD44, EpCAM, EZH2, and snail. These results
      clearly suggest the importance of miRNAs in the regulation of CSLC
      characteristics, and may serve as novel targets for therapy. 

PMID- 24734908
TI  - Single- and multiple-dose tolerability and pharmacokinetics of the CRTH2
      antagonist setipiprant in healthy male subjects.
AB  - Chemoattractant receptor-homologous molecule expressed on T helper (Th) 2 cells
      (CRTH2) is a G-protein-coupled receptor for prostaglandin D2 (PGD2), a key
      mediator in inflammatory disorders such as asthma and allergic rhinitis. In this
      study, we investigated the single- and multiple-dose tolerability and
      pharmacokinetics (PKs) of setipiprant, an orally active, potent, and selective
      CRTH2 antagonist. This randomized, double-blind, placebo-controlled study was
      performed in two parts in healthy male subjects. In study Part A, single oral
      doses of up to 2000 mg setipiprant or placebo were given to sequential groups of
      eight subjects each. Additionally, the impact of food on the PKs was investigated
      in one-dose group. In study Part B, two groups of subjects received 500 or 1000
      mg setipiprant or placebo b.i.d. during 5.5 days. At regular intervals,
      tolerability variables and plasma and urine levels of setipiprant were
      determined. Setipiprant was well tolerated after single- and multiple-dose
      administration. Headache was the most frequently reported adverse event. No
      treatment effect on tolerability variables was observed. After single- and
      multiple-dose administration, setipiprant was rapidly absorbed and followed a
      biphasic elimination pattern with an elimination half-life between 10 and 18 h.
      Steady-state conditions were reached after 2-3 days and setipiprant did not
      accumulate. Exposure to setipiprant was lower in the presence of food. Urinary
      excretion of unchanged setipiprant did not exceed 7% of the administered dose. In
      this entry-into-human study, setipiprant showed good tolerability and a favorable
      PK profile, thus warranting its development in the treatment of inflammatory
      disorders.

PMID- 24734909
TI  - Maxillary sinus grafting with autograft vs. fresh frozen allograft: a split-mouth
      histomorphometric study.
AB  - BACKGROUND: Surgical techniques as sinus floor augmentation have made it possible
      to increase the bone volume of the posterior maxilla so that implant placement
      may be feasible. A large variety of bone grafting materials have been utilized
      for sinus floor augmentation. A good alternative is allograft. Fresh frozen bone
      is harvested from live or cadaveric donors and then immediately frozen and stored
      at -80  degrees C. To date, studies about the effect of fresh frozen bone are
      scarce. OBJECTIVE: Evaluation of new bone formation, following maxillary sinus
      grafting with autograft vs. fresh frozen allograft. MATERIALS AND METHODS: A
      split-mouth edentulous design including 15 patients was used. Sinus floor
      augmentation was carried out using either autogenous bone harvested from the
      ramus area or fresh frozen bone from allogeneic femoral heads. The choice was
      determined randomly, using a randomized table. The grafted sinus was left to heal
      for 6 months. Biopsies were harvested from the lateral wall. The biopsies were
      used for bone histology and histomorphometric analysis. After collection of the
      biopsy, dental implants were placed. After a healing period of 6 months, the
      implants were loaded. RESULTS: Implant survival, histology, and histomorphometry
      of sinuses grafted with autogenous or fresh frozen bone were similar. The new
      bone formation took place predominantly around and in-between particles.
      CONCLUSIONS: The findings of the present study support the use of fresh frozen
      bone allografts for sinus floor augmentation.

PMID- 24734911
TI  - Environmental monitoring through protist next-generation sequencing
      metabarcoding: assessing the impact of fish farming on benthic foraminifera
      communities.
AB  - The measurement of species diversity represents a powerful tool for assessing the
      impacts of human activities on marine ecosystems. Traditionally, the impact of
      fish farming on the coastal environment is evaluated by monitoring the dynamics
      of macrobenthic infaunal populations. However, taxonomic sorting and morphology
      based identification of the macrobenthos demand highly trained specialists and
      are extremely time-consuming and costly, making it unsuitable for large-scale
      biomonitoring efforts involving numerous samples. Here, we propose to alleviate
      this laborious task by developing protist metabarcoding tools based on next
      generation sequencing (NGS) of environmental DNA and RNA extracted from sediment
      samples. In this study, we analysed the response of benthic foraminiferal
      communities to the variation of environmental gradients associated with salmon
      farms in Scotland. We investigated the foraminiferal diversity based on ribosomal
      minibarcode sequences generated by the Illumina NGS technology. We compared the
      molecular data with morphospecies counts and with environmental gradients,
      including distance to cages and redox used as a proxy for sediment oxygenation.
      Our study revealed high variations between foraminiferal communities collected in
      the vicinity of fish farms and at distant locations. We found evidence for
      species richness decrease in impacted sites, especially visible in the RNA data.
      We also detected some candidate bioindicator foraminiferal species. Based on this
      proof-of-concept study, we conclude that NGS metabarcoding using foraminifera and
      other protists has potential to become a new tool for surveying the impact of
      aquaculture and other industrial activities in the marine environment.

PMID- 24734910
TI  - Altering gene expression by aminocoumarins: the role of DNA supercoiling in
      Staphylococcus aureus.
AB  - BACKGROUND: It has been shown previously that aminocoumarin antibiotics such as
      novobiocin lead to immediate downregulation of recA expression and thereby
      inhibit the SOS response, mutation frequency and recombination capacity in
      Staphylococcus aureus. Aminocoumarins function by inhibiting the ATPase activity
      of DNA gyrase subunit B with a severe impact on DNA supercoiling. RESULTS: Here,
      we have analysed the global impact of the DNA relaxing agent novobiocin on gene
      expression in S. aureus. Using a novobiocin-resistant mutant, it became evident
      that the change in recA expression is due to gyrase inhibition. Microarray
      analysis and northern blot hybridisation revealed that the expression levels of a
      distinct set of genes were increased (e.g., recF-gyrB-gyrA, the rib operon and
      the ure operon) or decreased (e.g., arlRS, recA, lukA, hlgC and fnbA) by
      novobiocin. The two-component ArlRS system was previously found to decrease the
      level of supercoiling in S. aureus. Thus, downregulation of arlRS might partially
      compensate for the relaxing effect of novobiocin. Global analysis and gene
      mapping of supercoiling-sensitive genes did not provide any indication that they
      are clustered in the genome. Promoter fusion assays confirmed that the
      responsiveness of a given gene is intrinsic to the promoter region but
      independent of the chromosomal location. CONCLUSIONS: The results indicate that
      the molecular properties of a given promoter, rather than the chromosomal
      topology, dictate the responsiveness to changes in supercoiling in the pathogen
      Staphylococcus aureus.

PMID- 24734912
TI  - Maximum likelihood estimation of semiparametric mixture component models for
      competing risks data.
AB  - In the analysis of competing risks data, the cumulative incidence function is a
      useful quantity to characterize the crude risk of failure from a specific event
      type. In this article, we consider an efficient semiparametric analysis of
      mixture component models on cumulative incidence functions. Under the proposed
      mixture model, latency survival regressions given the event type are performed
      through a class of semiparametric models that encompasses the proportional
      hazards model and the proportional odds model, allowing for time-dependent
      covariates. The marginal proportions of the occurrences of cause-specific events
      are assessed by a multinomial logistic model. Our mixture modeling approach is
      advantageous in that it makes a joint estimation of model parameters associated
      with all competing risks under consideration, satisfying the constraint that the
      cumulative probability of failing from any cause adds up to one given any
      covariates. We develop a novel maximum likelihood scheme based on semiparametric
      regression analysis that facilitates efficient and reliable estimation.
      Statistical inferences can be conveniently made from the inverse of the observed
      information matrix. We establish the consistency and asymptotic normality of the
      proposed estimators. We validate small sample properties with simulations and
      demonstrate the methodology with a data set from a study of follicular lymphoma.

PMID- 24734913
TI  - Survivors' experiences of dysphagia-related services following head and neck
      cancer: implications for clinical practice.
AB  - BACKGROUND: It is known that people with dysphagia experience a number of
      negative consequences as a result of their swallowing difficulties following head
      and neck cancer management (HNC). However their perceptions and experiences of
      adjusting to dysphagia in the post-treatment phase, and the services received to
      assist this process, has not been studied. AIMS: To explore the lived experience
      of people with dysphagia following non-surgical treatment for HNC and examine
      their perceptions of service needs. METHODS & PROCEDURES: A demographically
      diverse group of 24 people who had received radiotherapy for HNC in the past five
      years, and experienced dysphagia as a result of treatment, were recruited using
      maximum variation sampling. Each participant took part in a semi-structured, in
      depth interview, where they reflected on their adjustment to, and recovery from
      dysphagia following treatment for HNC, as well as the dysphagia-related services
      they received during their treatment. Thematic analysis was used to analyse the
      transcripts and to identify key themes that emerged from the data. RESULTS: The
      main integrative theme was the desire for ongoing access to dysphagia-related
      services in order to adequately manage dysphagia. Within this integrative theme
      were five additional themes including: (1) entering the unknown: life after
      treatment for HNC; (2) making practical adjustments to live with dysphagia; (3)
      making emotional adjustments to live with dysphagia; (4) accessing support
      outside the hospital services; and (5) perceptions of dysphagia-related services.
      CONCLUSIONS & IMPLICATIONS: The interviews revealed the need for both greater
      access to services and a desire for services which address the multitude of
      issues faced by people with dysphagia following HNC in the post-treatment period.
      Speech and language therapists managing this caseload need to ensure post
      treatment services are available and address not only the physical but also the
      emotional and psychosocial changes impacting people with dysphagia in order to
      assist them to adjust to, and live successfully with dysphagia. Further research
      should be conducted to support the development of innovative services and to
      highlight dysphagia-related survivorship issues to governing bodies/policy
      makers.

PMID- 24734914
TI  - Effects of chitosan-essential oil coatings on safety and quality of fresh
      blueberries.
AB  - Chitosan coating plus different essential oils was developed and applied to fresh
      blueberries in order to find more natural treatments to preserve fresh fruit
      quality and safety during postharvest storage. Studies were 1st performed in
      vitro where wild-type Escherichia coli and Penicillium digitatum were grown in
      suitable media, and then subjected to 6 essential oils. Three compounds,
      carvacrol (CAR), cinnamaldehyde (CIN), and trans-cinnamaldehyde (ECIN) had high
      antimicrobial capacity and were selected for an in vivo study for postharvest
      storage of blueberries. The selected essential oils, 0.5% each, were added into a
      chitosan solution and coated on fresh blueberries. After storage at 5, 10, and 20
      degrees C for various days, fruit firmness and microbial populations were
      evaluated. The chitosan coating substantially decreased bacteria and yeasts/molds
      on the fruit, and all 3 essential oils added to the antimicrobial activities.
      Further dosage experiments showed that the antimicrobial activity remained even
      when lowering CAR concentration to 0.1% and ECIN to 0.2%. Chitosan, CAR, and ECIN
      also maintained fruit firmness. Our results suggest that chitosan coatings
      containing essential oils are effective in extending the shelf life of fresh
      blueberries. PRACTICAL APPLICATION: Blueberries are high-value fruit with strong
      antioxidant capacity and other health-promoting benefits. However, microbial food
      safety is an increasing concern, and decay and softening limits their
      storability. A combination of >= 0.1% CAR or >= 0.2% ECIN with a chitosan coating
      effectively reduced softening of fresh berries and decay by inhibiting microbial
      growth.

PMID- 24734915
TI  - Is Smoking a Risk Factor in Ocular Behcet Disease?
AB  - PURPOSE: To investigate the association between smoking and prognosis of ocular
      Behcet disease. MATERIAL/METHODS: Medical records of 202 patients with Behcet
      uveitis were collected retrospectively. Patients were assigned to two groups
      according to smoking habits. In group I, 72 patients were current smokers. In
      group II, 130 were nonsmokers. The localization of uveitis, time to resolution of
      uveitis, time to recurrences, visual acuities, and presence of cystoid macular
      edema were compared between groups. RESULTS: The demographic characteristics were
      similar in both groups. Smoking was not associated with types of uveitis with OR
      of 1.01 (95% CI, 0.99-1.04; p = 0.21) for anterior uveitis, 0.96 (95%CI, 0.90
      1.02; p = 0.18) for posterior uveitis, and 1.80 (95% CI, 0.75-2.77; p = 0.24) for
      panuveitis. The average times to inflammation resolution were 48 +/- 10.1 days in
      group I and 51 +/- 14 days in group II (p = 0.82). The average times to
      recurrence were 8.6 +/- 5 months for smokers and 9.1 +/- 7 months for nonsmokers
      (p = 0.43). Patients with CME in groups were 18 (25%) and 42 (32.3%),
      respectively (p = 0.08). CONCLUSIONS: Our findings suggest that smoking does not
      have a negative effect on the clinical findings and prognosis of uveitis in
      Behcet disease.

PMID- 24734916
TI  - Persistent abdominal symptoms post-travel: lessons learned.

PMID- 24734917
TI  - Consider prescribing tourism.

PMID- 24734918
TI  - Response to letter.

PMID- 24734919
TI  - Apropos "Point-of-care syndrome-based, rapid diagnosis of infections on
      commercial ships".

PMID- 24734920
TI  - Late seroconversion of acute schistosomiasis.

PMID- 24734921
TI  - Response to letter.

PMID- 24734922
TI  - Rate constant and mechanism of the reaction Cl + CFCl2H -> CFCl2 + HCl over the
      temperature range 298-670 K in N2 or N2/O2 diluent.
AB  - The rate constant of the reaction Cl + CFCl2H (k1) has been measured relative to
      the established rate constant for the reaction Cl + CH4 (k2) at 760 Torr. The
      measurements were carried out in Pyrex reactors using a mixture of CFCl2H, CH4,
      and Cl2 in either N2 or N2/O2 diluent. Reactants and products were quantified by
      GC/FID analysis. Cl atoms were generated by irradiation of the mixture with 360
      nm light to dissociate the Cl2 for temperatures up to ~550 K. At higher
      temperature, the Cl2 dissociated thermally, and no irradiation was used. Over the
      temperature range 298-670 K, k1 is consistently a factor of ~5 smaller than that
      of k2 with a nearly identical temperature dependence. The optimum non-Arrhenius
      rate constant is represented by the expression k1 = 1.14 * 10(-22) T(3.49) e(
      241/T) cm(3) molecule(-1) s(-1) with an estimated uncertainty of +/-15% including
      uncertainty in the reference reaction. CFCl3 formed from the reaction CFCl2 + Cl2
      (k3) is the sole product in N2 diluent. In ~20% O2 at 298 K, the CFCl3 product is
      suppressed. The rate constant of reaction 3 was measured relative to that of
      reaction 4 [CFCl2 + O2 (k4)] giving the result k3/k4 = 0.0031 +/- 0.0005 at 298
      K. An earlier experiment by others observed C(O)FCl to be the major product of
      reaction channel 4 [formed via the sequence, CFCl2(O2) -> CFCl2O -> C(O)FCl +
      Cl]. Our current experiments verified that there is a Cl atom chain reaction in
      the presence of O2 as required by this mechanism.

PMID- 24734923
TI  - Organocatalytic asymmetric Michael-Michael cascade for the construction of highly
      functionalized N-fused piperidinoindoline derivatives.
AB  - Application of indolin-3-one derivatives in a cascade reaction for efficient
      assembly of complex molecules is a much less explored research area. It is
      demonstrated that structurally interesting polysubstituted piperidino[1,2
      a]indoline compounds containing four contiguous stereocenters including one
      tetrasubstituted carbon center can be readily obtained with good yields (up to
      94% yield) and excellent enantioselectivities (up to >99% ee) by employing
      indolin-3-one derivatives as substrates via bifunctional catalysis. 

PMID- 24734925
TI  - More (on) airway eosinophilia in asthma.

PMID- 24734926
TI  - Changing practice: no need to stop ACE inhibition for venom immunotherapy.

PMID- 24734927
TI  - Regulation of IgE-mediated signalling in human basophils by CD32b and its role in
      Syk down-regulation: basic mechanisms in allergic disease.
AB  - BACKGROUND: CD32b has been previously demonstrated to modulate IgE-mediated
      secretion from human basophils. However, exploration of the implications of this
      regulation has been limited. One unstudied area is whether regulation of
      signalling by CD32 also alters some of the phenotypic changes induced by IgE
      mediated activation. The reported character of CD32-mediated signal transduction
      is not clear for human basophils and the two primary mechanisms considered
      important in this reaction predict different long-term outcomes, notably
      predicting different outcomes for down-regulation of syk expression. OBJECTIVE:
      Syk expression was considered a unique point of phenotypic control in human
      basophils and the role of CD32b in its regulation is explored in this study.
      However, initial pilot studies discovered that IL-3 could markedly up-regulate
      CD32 expression and first describing the consequences of this up-regulation
      became an additional focus of this study. METHODS: Human basophils were examined
      for the changes in IgE-mediated signalling during simultaneous engagement of
      CD32b. RESULTS: Preliminary experiments noted that CD32b could be up-regulated by
      IL-3 (3- to 12-fold). Both natural variation and induced up-regulation of CD32b
      modulated the efficacy of this receptor to inhibit IgE-mediated release.
      Signalling induced by engagement of CD32b (lyn, syk, SHP-1, or SHIP1
      phosphorylation) was more consistent with a mode of action involving SHIP1 rather
      than SHP-1. IgE-mediated down-regulation of syk expression was not altered by co
      engagement of CD32b, a result also consistent with a SHIP1-dependent mechanism of
      inhibition. CONCLUSIONS: Taken together these results suggest that the combined
      action of IgE and IgG could generate a natural mechanism, whereby the significant
      variation in syk expression in allergic subjects occurs without necessarily also
      inducing mediator release.

PMID- 24734929
TI  - Nano-hydroxyapatite and nano-titanium dioxide exhibit different subcellular
      distribution and apoptotic profile in human oral epithelium.
AB  - Nanomaterials (NMs) such as titanium dioxide (nano-TiO2) and hydroxyapatite (nano
      HA) are widely used in food, personal care, and many household products. Due to
      their extensive usage, the risk of human exposure is increased and may trigger
      NMs specific biological outcomes as the NMs interface with the cells. However,
      the interaction of nano-TiO2 and nano-HA with cells, their uptake and subcellular
      distribution, and the cytotoxic effects are poorly understood. Herein, we
      characterized and examined the cellular internalization, inflammatory response
      and cytotoxic effects of nano-TiO2 and nano-HA using TR146 human oral buccal
      epithelial cells as an in vitro model. We showed both types of NMs were able to
      bind to the cellular membrane and passage into the cells in a dose dependent
      manner. Strikingly, both types of NMs exhibited distinct subcellular distribution
      profile with nano-HA displaying a higher preference to accumulate near the cell
      membrane compared to nano-TiO2. Exposure to both types of NMs caused an elevated
      reactive oxygen species (ROS) level and expression of inflammatory transcripts
      with increasing NMs concentration. Although cells treated with nano-HA induces
      minimal apoptosis, nano-TiO2 treated samples displayed approximately 28% early
      apoptosis after 24 h of NMs exposure. We further showed that nano-TiO2 mediated
      cell death is independent of the classical p53-Bax apoptosis pathway. Our
      findings provided insights into the potential cellular fates of human oral
      epithelial cells as they interface with industrial grade nano-HA and nano-TiO2. 

PMID- 24734930
TI  - Health economics of percutaneous hemodynamic support in the treatment of high
      risk cardiac patients: a systematic appraisal of the literature.
AB  - This article systematically appraises the findings and conclusions derived from
      six recent studies of the economic impact and relative value of using
      percutaneous ventricular assist devices to render short-term hemodynamic support
      to high-risk patients with particular attention to the settings of cardiogenic
      shock and percutaneous coronary interventions. Although the extant body of
      literature is still growing, these studies offer evidence and insight regarding
      the health economics of traditional and emerging technologies in this treatment
      domain, and generally find the latter to be cost-effective in the long term. As
      the incidence of heart disease rises and the attendant economic burden of
      healthcare climbs, technologies for mitigating cardiovascular illness will be the
      target for more robust empirical evidence to justify the comparative value of
      minimally invasive hemodynamic support interventions in the armamentarium of
      treatment options available to physicians. 

PMID- 24734931
TI  - Study on influence of age, gender and genetic variants on lactose intolerance and
      its impact on milk intake in adult Asian Indians.
AB  - BACKGROUND: Lactase non-persistence (LNP) has been associated with the CC
      genotype of -13910C > T and GG genotype of -22018G > A polymorphisms present
      upstream of the lactase gene. Lactose intolerance (LI) is caused when
      gastrointestinal symptoms develop in individuals with low lactase activity.
      OBJECTIVE: To analyse association of LNP genotype and LI symptoms with milk
      intake and determine whether factors such as age, gender and genotype affect LI
      status. SUBJECTS AND METHODS: Genetic analysis and lactose tolerance test (LTT)
      were performed on 205 healthy Indian adults. The pattern of milk consumption was
      recorded using a dietary questionnaire. RESULTS: LI was strongly associated with 
      13910CC genotype (OR = 10.28, 95% CI = 2.32-45.55, p = 0.002). Females were found
      to be at a higher risk of developing LI (OR = 2.47, 95% CI = 1.33-4.59, p =
      0.004). The association of the >=50 years age group with LI was marginally
      significant (OR = 1.86, 95% CI = 0.995-3.47, p = 0.05). Frequency and quantity of
      milk intake were lower in subjects belonging to the LNP genotype and LI groups (p
      < 0.05). CONCLUSIONS: Subject study suggests that gender and genotype may be
      associated with development of LI. Association of age with LI was marginal. The
      data also indicate that LNP genotype and LI may play a role in influencing milk
      intake in individuals.

PMID- 24734932
TI  - Extravascular migratory metastasis in gynaecological carcinosarcoma.
AB  - AIMS: Extravascular migratory metastasis (EVMM) is a potential mechanism of
      tumour spread reported most extensively in cutaneous melanoma. It has not been
      described previously in gynaecological malignancies. We describe EVMM in four
      gynaecological carcinosarcomas. METHODS AND RESULTS: Extravascular migratory
      metastasis was observed in an ovarian carcinosarcoma during routine diagnostic
      assessment. Twenty-three additional, randomly selected gynaecological
      carcinosarcomas (11 tubo-ovarian and 12 endometrial) were examined
      retrospectively and EVMM was identified in three of these. Other than the index
      case, EVMM was a focal finding, identified in 12-18% of slides. The malignant
      cells demonstrating EVMM appeared sarcomatoid and were distributed abluminally,
      partly or completely surrounding the endothelium. Affected vessels often showed
      mural fibrin deposition. Immunohistochemistry for alpha-smooth muscle actin
      (SMA), CD31, CD34, D2-40, laminin and type IV collagen was performed on the EVMM
      positive cases. The perivascular malignant cells showed more consistent SMA and
      laminin immunoreactivity than the non-vascular tumour elements. CONCLUSIONS:
      Extravascular migratory metastasis is a hitherto unrecognized mechanism of tumour
      spread in gynaecological carcinosarcomas. The perivascular tumour cells appear to
      adopt a pericytic phenotype, and this may represent a specific pattern of
      epithelial-mesenchymal transition. Further studies with pericyte-specific
      immunohistological markers may better demonstrate the presence and possible
      prognostic significance of EVMM in gynaecological tumours.

PMID- 24734933
TI  - A review of heat transfer phenomena and the impact of moisture on firefighters'
      clothing and protection.
AB  - Protective clothing with high insulation properties helps to keep the wearer safe
      from flames and other types of hazards. Such protection presents some drawbacks
      since it hinders movement and decreases comfort, in particular due to heat
      stress. In fact, sweating causes the accumulation of moisture which directly
      influences firefighters' performance, decreasing protection due to the increase
      in radiant heat flux. Vaporisation and condensation of hot moisture also induces
      skin burn. To evaluate the heat protection of protective clothing, Henrique's
      equation is used to predict the time leading to second-degree burn. The influence
      of moisture on protection is complex, i.e., at low radiant heat flux, an increase
      in moisture content increases protection, and also changes thermal properties.
      Better understanding of heat and mass transfer in protective clothing is required
      to develop enhanced protection and to prevent burn injuries. PRACTITIONER
      SUMMARY: This paper aims to contribute to a better understanding of heat and mass
      transfer inside firefighters' protective clothing to enhance safety. The focus is
      on the influence of moisture content and the prevention of steam burn.

PMID- 24734934
TI  - Mammographic and clinicopathological features of triple-negative breast cancer.
AB  - OBJECTIVE: Triple-negative breast cancer (TNBC) lacks effective treatment and has
      a poor prognosis. This study assessed mammographic findings and
      clinicopathological features of TNBC by comparing with non-TNBC in order to
      improve clinical diagnosis of TNBC. METHODS: A total of 426 patients with
      pathologically confirmed breast cancer were retrospectively assigned into two
      groups, TNBC (n = 54) and non-TNBC (n = 372), and then analysed. RESULTS: TNBC
      frequently showed a high histological grade, presented with a mass (79.6%) and
      was less frequently associated with focal asymmetric density (11.1%),
      microcalcifications (5.6%) and distortion (3.7%) on mammography. TNBC
      mammographic masses were most frequently round/oval (58.1%) or lobular (30.2%) in
      shape and were less frequently irregular in shape (11.6%). Masses with
      circumscribed margins were the most frequent (37.2%), with microlobulated (25.6%)
      and obscured (16.3%) margins being commonly observed, but masses with spiculated
      margins were rare (9.3%). CONCLUSION: TNBC could have distinct mammographic and
      clinicopathological features compared with non-TNBC, and thus mammography may be
      useful in the diagnosis of TNBC. ADVANCES IN KNOWLEDGE: This study demonstrated
      distinct mammographic and clinicopathological features to help in diagnosis of
      Chinese patients with TNBC.

PMID- 24734935
TI  - Complications of rotator cuff surgery-the role of post-operative imaging in
      patient care.
AB  - When pain or disability occurs after rotator cuff surgery, post-operative imaging
      is frequently performed. Post-operative complications and expected post-operative
      imaging findings in the shoulder are presented, with a focus on MRI, MR
      arthrography (MRA) and CT arthrography. MR and CT techniques are available to
      reduce image degradation secondary to surgical distortions of native anatomy and
      implant-related artefacts and to define complications after rotator cuff surgery.
      A useful approach to image the shoulder after surgery is the standard
      radiography, followed by MRI/MRA for patients with low "metal presence" and CT
      for patients who have a higher metal presence. However, for the assessment of
      patients who have undergone surgery for rotator cuff injuries, imaging findings
      should always be correlated with the clinical presentation because post-operative
      imaging abnormalities do not necessarily correlate with symptoms. 

PMID- 24734936
TI  - Effectiveness and security of CT-guided percutaneous implantation of (125)I seeds
      in pancreatic carcinoma.
AB  - OBJECTIVE: To assess the effectiveness and security of CT-guided percutaneous
      implantation of iodine-125 ((125)I)-labelled seeds in pancreatic carcinoma.
      METHODS: A total of 36 patients (25 males and 11 females) with an average age of
      57 years (range, 39-84 years) were enrolled and categorized into Stage III (27
      cases) and Stage IV (9 cases) of pancreatic cancer. There were 3 tumours in the
      pancreatic head and 33 tumours in the pancreatic body or tail. The average
      diameter of the tumours was 37.1 mm (range, 15-65 mm). The implantation of (125)I
      seeds was performed by using 18-G needles (length, 150-200 mm) through the
      anterior, lateral and posterior approaches. Then, (125)I seeds were loaded and
      released into the lesions. RESULTS: Implantations were performed via the anterior
      (23 patients), lateral (9 patients) and posterior (4 patients) approaches. During
      implantation, 3-14 punctures were performed for each patient, and a total of 164
      punctures were recorded. Meanwhile, a total of 657 seeds were implanted with an
      average of 25.27 (range, 12-50) seeds per patient, and the success rate was 100%.
      The activity of each seed ranged from 0.55 to 0.65 mCi. A main adverse event
      occurred in one puncture and minor events in seven punctures. No significant
      relationship between the punctures or adverse events was identified. No serious
      complication was detected after the implantations during follow-up visits.
      CONCLUSION: This study suggested that CT-guided percutaneous implantation of
      (125)I seeds in a pancreatic carcinoma was relatively safe and effective for
      treating unresectable pancreatic cancer. ADVANCES IN KNOWLEDGE: The CT-guided
      percutaneous implantation of (125)I seeds in unresectable pancreatic cancer
      showed highly successful rates without serious complications.

PMID- 24734937
TI  - Resistive intrarenal index: myth or reality?
AB  - In renal diagnosis, the B-mode ultrasound is used to provide an accurate study of
      the renal morphology, whereas the colour and power Doppler are of strategic
      importance in providing qualitative and quantitative information about the renal
      vasculature, which can also be obtained through the assessment of the resistive
      index (RI). To date, this is one of the most sensitive parameters in the study of
      kidney diseases and allows us to quantify the changes in renal plasma flow. If a
      proper Doppler ultrasound examination is carried out and a critical analysis of
      the values obtained is performed, the RI measurement at the interlobar artery
      level has been suggested in the differential diagnosis between nephropathies. The
      aim of this review is to highlight the pathological conditions in which the study
      of intrarenal RI provides useful information about the pathophysiology of renal
      diseases in both the native and the transplanted kidneys.

PMID- 24734938
TI  - Multimodality imaging features, metastatic pattern and clinical outcome in adult
      extraskeletal Ewing sarcoma: experience in 26 patients.
AB  - OBJECTIVE: To describe the multimodality imaging features, metastatic pattern and
      clinical outcome in adult extraskeletal Ewing sarcoma (EES). METHODS: In this
      institutional review board-approved, health insurance portability and
      accountability act-compliant retrospective study, we included 26 patients (17
      females and 9 males; mean age, 36 years; range, 18-85 years) with pathologically
      confirmed EES seen at our institute between 1999 and 2011, who had imaging of
      primary tumour. Imaging of primary tumour in all 26 patients and follow-up
      imaging in 23 was reviewed by two radiologists in consensus. Clinical data were
      extracted from electronic medical records. RESULTS: The most common primary sites
      were the torso (n = 13), extremities (n = 10) and head and neck (HN) region (n =
      3). The mean tumour size was 9 cm (range, 3-22 cm); tumours of the torso were
      larger than those of other areas (p > 0.05). Compared with the skeletal muscle,
      tumours were isodense on CT (21/21), hypointense (n = 5) to isointense (n = 14)
      on T1 weighted image, hyperintense on T2 weighted image (19/19) and were fluorine
      18 fludeoxyglucose ((18)F-FDG)-avid [10/10; mean maximum standardized uptake
      value of 7 (range, 3-11)]. Necrosis (15/26), haemorrhage (5/26) and adjacent
      organ invasion (14/26) were present without calcification. Median follow-up was
      16 months. 5 patients had local recurrence (torso, 3; extremity, 1; and HN, 1).
      Metastases developed in 11 patients (torso, 7; extremities, 3; and HN, 1; p >
      0.05); 8 at presentation, most commonly to lung (9/11), peritoneum (4/11),
      muscles (4/11) and lymph nodes (4/11). Nine patients (torso, 7; extremity, 1; and
      HN, 1) died (10 months median survival) (p > 0.05). CONCLUSION: Adult EESs are
      large tumours, which frequently invade adjacent organs and metastasize to the
      lung. EESs of the torso are larger, have more frequent metastases and poorer
      outcomes. ADVANCES IN KNOWLEDGE: Adult EESs of the torso have poor outcomes
      compared with other EESs.

PMID- 24734940
TI  - Rapid prototyping of multichannel microfluidic devices for single-molecule DNA
      curtain imaging.
AB  - Single-molecule imaging and manipulation of biochemical reactions continues to
      reveal numerous biological insights. To facilitate these studies, we have
      developed and implemented a high-throughput approach to organize and image
      hundreds of individual DNA molecules at aligned diffusion barriers. Nonetheless,
      obtaining statistically relevant data sets under a variety of reaction conditions
      remains challenging. Here, we present a method for integrating high-throughput
      single-molecule "DNA curtain" imaging with poly(dimethylsiloxane) (PDMS)-based
      microfluidics. Our benchtop fabrication method can be accomplished in minutes
      with common tools found in all molecular biology laboratories. We demonstrate the
      utility of this approach by simultaneous imaging of two independent biochemical
      reaction conditions in a laminar flow device. In addition, five different
      reaction conditions can be observed concurrently in a passive linear gradient
      generator. Combining rapid microfluidic fabrication with high-throughput DNA
      curtains greatly expands our capability to interrogate complex biological
      reactions. 

PMID- 24734941
TI  - Diagnostic accuracy of intraoperative consultation (frozen section) in borderline
      ovarian tumours and factors associated with misdiagnosis.
AB  - The objective of our study was to evaluate the accuracy of frozen section (FS) in
      borderline ovarian tumours (BOT) and to define the factors associated with
      misdiagnosis during FS evaluation. We performed a retrospective review of
      patients who underwent exploratory laparotomy for an adnexal mass, from January
      2007 to July 2012, at a tertiary oncology centre in Turkey. Patients with a
      diagnosis of BOT either in FS or in permanent pathology were identified.
      Agreement between FS diagnosis and permanent histology was observed in 37/59
      patients (62.7%), which gave a sensitivity and a positive predictive value of
      71.2% and 84.1%, respectively. In patients with a diagnosis of BOT by frozen
      section only (n = 44), the diagnosis was consistent with permanent histopathology
      in 37/44 patients (84.1%). Frozen section interpreted a malignant tumour as BOT
      (under-diagnosis) in 6/44 (13.6%) of cases and interpreted a benign lesion as BOT
      (over-diagnosis) in 1/44 (2.3%) of cases. Slide review of discrepant cases
      revealed that major pathological causes of under-diagnosis were misinterpretation
      and sampling errors. Univariate analysis showed that presence of bilateral tumour
      and positive peritoneal cytology were associated with under-diagnosis. We
      concluded that, despite significant risk of under-diagnosis, FS analysis is an
      accurate method for intraoperative diagnosis of BOTs.

PMID- 24734939
TI  - Recent developments and best practice in brachytherapy treatment planning.
AB  - Brachytherapy has evolved over many decades, but more recently, there have been
      significant changes in the way that brachytherapy is used for different treatment
      sites. This has been due to the development of new, technologically advanced
      computer planning systems and treatment delivery techniques. Modern, three
      dimensional (3D) imaging modalities have been incorporated into treatment
      planning methods, allowing full 3D dose distributions to be computed. Treatment
      techniques involving online planning have emerged, allowing dose distributions to
      be calculated and updated in real time based on the actual clinical situation. In
      the case of early stage breast cancer treatment, for example, electronic
      brachytherapy treatment techniques are being used in which the radiation dose is
      delivered during the same procedure as the surgery. There have also been
      significant advances in treatment applicator design, which allow the use of
      modern 3D imaging techniques for planning, and manufacturers have begun to
      implement new dose calculation algorithms that will correct for applicator
      shielding and tissue inhomogeneities. This article aims to review the recent
      developments and best practice in brachytherapy techniques and treatments. It
      will look at how imaging developments have been incorporated into current
      brachytherapy treatment and how these developments have played an integral role
      in the modern brachytherapy era. The planning requirements for different
      treatments sites are reviewed as well as the future developments of brachytherapy
      in radiobiology and treatment planning dose calculation. 

PMID- 24734942
TI  - Accuracy of three activity monitors in patients with chronic obstructive
      pulmonary disease: a comparison with video recordings.
AB  - Low physical activity and sedentary behaviour characterise the lives of patients
      with chronic obstructive pulmonary disease (COPD). Using activity monitors,
      assessment of both aspects are possible, but many outcomes are not well
      validated. The aim of this study was to assess the accuracy and equivalency of
      three activity monitors regarding steps, body position and their ability to
      differentiate between periods of physical activity and inactivity. Fifteen
      patients with COPD (8 females; median (interquartile range, IQR) age, 64 (59-69)
      years; forced expiratory volume in 1 second, 37 (28-48)% predicted; 6-minute walk
      distance, 444 (410-519) m) were enrolled. The DynaPort ADL-monitor, the DynaPort
      MiniMod monitor and the SenseWear Armband Pro 3 monitor were assessed. Subjects
      performed a structured protocol alternating physical activity and inactivity
      while simultaneously wearing all three monitors and being video recorded. The
      mean difference (limits of agreement) in step count from monitors compared to
      manual step count was -69 (-443 to 305) for the ADL-monitor, -19 (-141 to 103)
      for the MiniMod and -479 (-855 to -103) for the SenseWear Armband. Compared to
      the video, the sitting time was 97 (94-100)% when measured by the ADL-monitor and
      121 (110-139)% by the MiniMod. Standing time was 114 (107-122)% when measured by
      the ADL-monitor and 68 (47-106)% by the MiniMod. Activity monitors are not
      equivalent in their abilities to detect steps or body positions. The choice of
      monitor should be based on the particular outcome of interest.

PMID- 24734943
TI  - Shared decision making in dermatology: asking patients, 'What is important to
      you?'.

PMID- 24734944
TI  - The outstanding record of clinical trials in the British Journal of Dermatology.

PMID- 24734945
TI  - The association between beta-blockers and melanoma survival: evidence of absence
      or absence of evidence?

PMID- 24734946
TI  - Inflammasome activation and vitiligo/nonsegmental vitiligo progression.
AB  - BACKGROUND: Polymorphisms of NLR (nucleotide-binding domain and leucine rich
      repeat containing) family, pyrin domain containing protein 1 (NLRP1) have been
      found in patients with vitiligo/nonsegmental vitiligo (NSV), and increased NLRP1
      expression has been detected in the leading edge of lesional skin biopsies.
      OBJECTIVES: To evaluate the presence and intensity of NLRP1 immunostaining in
      lesional and perilesional skin of patients with vitiligo/NSV and to search for
      possible correlations between NLRP1 and interleukin (IL)-1beta expression,
      lymphocytic infiltrates and disease activity. METHODS: Of 14 consecutive
      vitiligo/NSV patients, eight had active disease [Vitiligo European Task Force
      (VETF) spreading score +1 to +5], one patient had stable disease and five
      patients had regressive disease (VETF spreading score -1 to -3). We performed
      immunostaining for NLRP1, B and T lymphocytes, IL-1beta and kallikrein 7 on
      lesional and perilesional vitiligo skin. RESULTS: NLRP1 and IL-1beta
      immunostaining in perilesional vitiligo/NSV skin was significantly associated
      with progressive disease (P = 0.009 and 0.04, respectively) and performed better
      than the simple detection of lymphocytic infiltrates. CONCLUSIONS: Our findings
      suggest that markers of the NLRP1 inflammasome could be a useful test for
      assessing disease activity in addition to the detection of inflammatory
      infiltrates in the progressing margins of vitiligo/NSV lesions.

PMID- 24734947
TI  - Serum autoantibodies against the dermal-epidermal junction in patients with
      chronic pruritic disorders, elderly individuals and blood donors prospectively
      recruited.
AB  - BACKGROUND: Bullous pemphigoid (BP) is a subepidermal blistering autoimmune
      disease characterized by autoantibodies against two structural proteins of the
      epidermal basal membrane zone (BMZ), BP180 (type XVII collagen) and BP230.
      Patients are usually old and suffer from severe pruritus. Advanced age and severe
      pruritus have been hypothesized as potential risk factors for the development of
      autoantibodies in BP. OBJECTIVES: To prospectively determine anti-BMZ antibodies
      in sera from patients with advanced age and/or pruritus compared with regular
      blood donors. METHODS: Sera from (i) patients with chronic pruritic skin
      disorders (PSD, n = 78; mean age 62 years), (ii) patients with noninflammatory
      skin disease aged >= 70 years (n = 93; mean age 78 years), and (iii) blood donors
      (n = 50; mean age 41 years) were included. A large panel of validated test
      systems used for routine diagnosis were employed comprising indirect
      immunofluorescence (IF) microscopy on monkey oesophagus and human salt-split
      skin, BP180 NC16A- and BP230-specific enzyme-linked immunosorbent assay (ELISA)
      systems, and immunoblotting with various substrates, including LAD-1 (the soluble
      ectodomain of BP180), BP180, BP230, laminin 332, p200 antigen, laminin gamma1 and
      type VII collagen. RESULTS: No statistically significant difference was seen
      between the three study groups. The same result was obtained when data for IF
      microscopy, ELISA and immunoblotting were analysed separately. CONCLUSIONS:
      Neither advanced age nor chronic pruritus have been verified as risk factors for
      autoantibodies against the epidermal BMZ.

PMID- 24734951
TI  - 2'-hydroxyflavanone induces apoptosis of human osteosarcoma 143 B cells by
      activating the extrinsic TRAIL- and intrinsic mitochondria-mediated pathways.
AB  - Flavanones demonstrate a propensity to antiproliferation and induce apoptosis of
      malignant cells. Among the 4 flavanones under study, 2'-hydroxyflavanone
      exhibited the greatest potency to reduce the cell viability of 143 B cells in 4
      osteosarcoma cells. Flow cytometry analysis showed that 2'-hydroxyflavanone
      increased the hypodiploid cells in the sub-G1 phase but resulted in the reduced
      DNA content in the G0/G1 phase in 143 B cells. The 2'-hydroxyflavanone-induced
      apoptosis in 143 B cells was confirmed by 4'-6-diamidino-2-phenylindole staining
      and mitochondrial membrane potential (Deltapsim) assay. Increasing expressions of
      tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and death
      receptor 5 (DR5) were found in 2'-hydroxyflavanone-treated cells. Moreover, 2'
      hydroxyflavanone increased the expressions of B-cell lymphoma-extra small,
      cytochrome c, and cleavage poly (ADP-ribose) polymerase but downregulated B-cell
      lymphoma/leukemia-2expressions in 143 B cells. Furthermore, in vivo experiments
      showed that 2'-hydroxyflavanone inhibited the tumor growth of 143 B cells. 2'
      hydroxyflavanone induced the apoptosis of 143 B cells via the extrinsic TRAIL-
      and intrinsic mitochondrial-dependent pathways, indicating its potential for
      inducing cancer apoptosis in osteosarcoma. 

PMID- 24734952
TI  - The emotional memory effect in Alzheimer's disease: emotional words enhance
      recollective experience similarly in patients and control participants.
AB  - The purpose of the present study was to investigate emotional memory enhancement
      (EME) in Alzheimer's disease (AD). In particular, we were interested in exploring
      which memory process (i.e., recollection or familiarity) could be improved by
      emotional information in the course of the disease. Eighteen AD patients were
      compared with 15 normal controls on the Remember/Know/Guess paradigm following
      encoding of emotional and neutral words. AD patients' recollective experience was
      improved for emotional compared to neutral words to the same extent as that of
      normal controls, whereas emotion had no effect on participants' memory
      performance involving familiarity processes. Our results showed that AD patients'
      memory can be enhanced qualitatively but not quantitatively by an emotional
      material. Furthermore, we found that AD patients were as able as normal controls
      to benefit from the emotional content of information to improve the recollection
      of details. 

PMID- 24734954
TI  - Multidrug resistance protein-1 expression, function and polymorphisms in patients
      with rheumatoid arthritis not responding to methotrexate.
AB  - OBJECTIVE: To study the expression, function and polymorphism of MDR-1 protein on
      the peripheral blood lymphocytes in patients with RA following treatment with MTX
      and its relationship with response to therapy. METHODS: RA patients naive to
      MTX/DMARD- and glucocorticoid were enrolled. Expression and function of MDR-1 was
      carried out by flow cytometry at baseline and after 4 months of therapy. MDR-1
      expression was measured by relative fluorescence intensities and percentage of
      positive cells. MDR-1 function was assessed by Rhodamine efflux in presence or
      absence of verapamil. Patients with reduction in disease activity score 28 >=1.2
      were defined as responders and <1.2 as non-responders. Three single nucleotide
      polymorphisms in MDR-1 gene, 3435T, 1236T and 2677T/A were studied. RESULTS:
      Fifty-two patients of RA were grouped into responders (n = 41), and non
      responders (n = 11) as per the defined criteria. There was no difference between
      the groups in terms of age, sex ratio or duration of illness, MTX dose and follow
      up duration. The expression and function of the MDR-1 protein reduced
      significantly in the responder group after the treatment with MTX when compared
      to the baseline evaluation. The decrease was significant when compared to the non
      responders at the fourth month. MDR-1 expression and function either increased or
      remained the same in the non-responder group after treatment with MTX. MTX
      unresponsiveness was not related to any of the three polymorphisms studied.
      CONCLUSION: Persistent expression and function of MDR-1 identifies a subset of RA
      patients not responding to MTX. Its early recognition may help in appropriately
      modulating therapy.

PMID- 24734953
TI  - Transcriptome profiling of genes and pathways associated with arsenic toxicity
      and tolerance in Arabidopsis.
AB  - BACKGROUND: Arsenic (As) is a toxic metalloid found ubiquitously in the
      environment and widely considered an acute poison and carcinogen. However, the
      molecular mechanisms of the plant response to As and ensuing tolerance have not
      been extensively characterized. Here, we report on transcriptional changes with
      As treatment in two Arabidopsis accessions, Col-0 and Ws-2. RESULTS: The root
      elongation rate was greater for Col-0 than Ws-2 with As exposure. Accumulation of
      As was lower in the more tolerant accession Col-0 than in Ws-2. We compared the
      effect of As exposure on genome-wide gene expression in the two accessions by
      comparative microarray assay. The genes related to heat response and oxidative
      stresses were common to both accessions, which indicates conserved As stress
      associated responses for the two accessions. Most of the specific response genes
      encoded heat shock proteins, heat shock factors, ubiquitin and aquaporin
      transporters. Genes coding for ethylene-signalling components were enriched in As
      tolerant Col-0 with As exposure. A tolerance-associated gene candidate encoding
      Leucine-Rich Repeat receptor-like kinase VIII (LRR-RLK VIII) was selected for
      functional characterization. Genetic loss-of-function analysis of the LRR-RLK
      VIII gene revealed altered As sensitivity and the metal accumulation in roots.
      CONCLUSIONS: Thus, ethylene-related pathways, maintenance of protein structure
      and LRR-RLK VIII-mediated signalling may be important mechanisms for toxicity and
      tolerance to As in the species. Here, we provide a comprehensive survey of global
      transcriptional regulation for As and identify stress- and tolerance-associated
      genes responding to As.

PMID- 24734955
TI  - Safety and efficacy of embryonic stem cell microenvironment in a leukemia mouse
      model.
AB  - The embryonic stem cell (ESC) microenvironment can promote the proliferation of
      terminal cells and reduce the invasiveness of tumor cells. However, implanting
      ESCs directly in vivo can result in tumorigenicity, immune rejection after
      differentiation, and graft-versus-host reaction. Therefore, safety is very
      important in the clinical application of ESCs. We injected ESCs modified with a
      suicide gene into a leukemia mouse model through peripheral blood to observe the
      treatment effectiveness. In addition, according to the pre-test, we set the time
      point of differentiation after transplantation and then activated the suicide
      gene to kill the ESCs that we had initially implanted, hoping to avoid the risks
      mentioned earlier. Our results indicated that the body weight and survival rates
      of mice treated with an ESC microenvironment increased, and leukemic cells in
      peripheral blood and bone marrow decreased compared with untreated mice. There
      was no obvious teratoma in mice that received ESC therapy and induced the suicide
      gene at the proper time during the observation period, while an apparent teratoma
      was observed in the lungs of mice which received ESC therapy and never induced
      the suicide gene. Therefore, the ESC microenvironment can promote self-healing of
      the in vivo microenvironment. Inducing the suicide gene at the appropriate time
      can reduce or even avoid tumorigenicity and immune rejection after
      transplantation of ESCs in vivo and improve the safety of their clinical
      application. 

PMID- 24734956
TI  - Unsplinted implants and teeth supporting maxillary removable partial dentures
      retained by telescopic crowns: a retrospective study with >6 years of follow-up.
AB  - OBJECTIVES: Data regarding tooth- and implant-supported maxillary removable
      partial dentures (TIRPDs) are scarce. The objective of this research was to
      perform a retrospective evaluation of the clinical long-term outcome of maxillary
      TIRPDs rigidly retained via telescopic crowns in patients undergoing supportive
      post-implant therapy (SIT). MATERIAL AND METHODS: The inclusion criteria were met
      by 26 patients restored with maxillary TIRPDs between 1997 and 2011 in a private
      practice. Primary crowns (Marburg double crowns, MDCs) on teeth were cemented,
      whereas those on implants were screw-retained. Using patient records and data
      from a cross-sectional clinical examination in 2013, the survival rates of the
      teeth, implants and prostheses, together with the biological and technical
      complications, were analyzed. RESULTS: After 6.12 +/- 3.80 (range: 2-16) years of
      loading, 23 non-smoking patients with 23 dentures supported by 60 implants and 66
      teeth were available for assessment. Nine teeth (survival rate: 86.36%) were
      lost, whereas 1 implant (survival rate: 98.36%) failed because of peri
      implantitis. Although 30 implants (50%) in 16 patients (69.57%) showed bleeding
      on probing (BOP+), no further peri-implantitis was observed. The mean peri
      implant probing depth (PPD) was 3.68 +/- 0.71 mm. All dentures were functional
      and required technical maintenance efforts amounting to 0.128 treatments per
      patient per year (T/P/Y). CONCLUSIONS: Within the limitations of this study, we
      conclude that TIRPDs retained via MDCs may represent a viable treatment option
      for patients with residual maxillary teeth.

PMID- 24734957
TI  - Survival benefit of radioembolization for inoperable hepatocellular carcinoma
      using yttrium-90 microspheres.
AB  - BACKGROUND AND AIM: Transarterial radioembolization with yttrium-90 microspheres
      is one treatment option for inoperable hepatocellular carcinoma. We compared the
      survival in a cohort of patients receiving radioembolization or no
      radioembolization. METHODS: The data of 46 patients referred for
      radioembolization was retrospectively reviewed. The patient, tumor
      characteristics, and the survival were compared in the two groups. The
      independent predictors for survival were studied with multivariate analysis. The
      side-effects and the complication of radioembolization-induced liver disease was
      recorded. RESULTS: Thirty patients received radioembolization; 16 patients did
      not. The two groups did not differ in the mean age, Child-Pugh classes, Barcelona
      Clinic of Liver Cancer (BCLC) stages, tumor types, sum of diameter of the two
      biggest tumors, and extent of portal vein invasion. Those with BCLC stage C
      tumor, with portal vein thrombus, or with less than three nodules had
      significantly longer survival after radioembolization. There was a trend of
      longer survival in patients with Child-Pugh A liver function, or with BCLC stage
      B tumor after radioembolization. The median survival was more than 31.9 months,
      14.5 months, and 5.2 months in patients with BCLC stage A, B, and C tumors. The
      independent predictors for longer survival were Child-Pugh class, tumor diameter
      sum, BCLC stage, and receiving radioembolization. Grade 2 irradiation-induced
      gastritis occurred in three patients (10%). Radioembolization-induced liver
      disease occurred in four patients (13%). CONCLUSIONS: Radioembolization may
      prolong survival for patients with inoperable hepatocellular carcinoma.
      Radioembolization-induced liver disease occurred and should be further studied.

PMID- 24734958
TI  - The non-medical use of tramadol in the UK: findings from a large community
      sample.
AB  - BACKGROUND: Prescription drug misuse has become a public health problem in
      several developed countries. In the UK, there has been no increase in people
      seeking treatment for prescription drug dependence, but there has been a
      progressive rise in fatal overdoses involving tramadol. OBJECTIVES: To explore
      the source, motivations for use and patterns of use of tramadol in the UK.
      METHODS: We conducted anonymous online survey of drug use and related behaviours
      as part of an ongoing drug trend monitoring initiative. We included questions
      assessing the patterns of use, source and function of tramadol. RESULTS: UK
      Survey respondents (n = 7360) were predominantly young (mean age 29), and 90%
      reported being employed or studying. Less than 1% reported past-year use of
      heroin or methadone, but about 1/3 reported past-year use of cocaine. 326 (5% of
      respondents) reported having used tramadol in the preceding year, usually
      obtained by prescription but in 1/3 of cases from a friend; rarely from a dealer
      or from the internet. Most used the drug for pain relief, but 163 respondents
      (44%) reported using tramadol for reasons other than pain relief - particularly,
      using it to relax, to sleep, to get high or to relieve boredom. Nineteen per cent
      took doses higher than prescribed, and 10% reported difficulty discontinuing.
      Twenty-eight per cent combined tramadol with alcohol or other drugs to enhance
      its effect. CONCLUSION: Misuse and sharing of tramadol, supplied by prescription,
      was common.

PMID- 24734959
TI  - Rapid HPLC-MS method for the simultaneous determination of tea catechins and
      folates.
AB  - An effective and rapid HPLC-MS method for the simultaneous separation of the
      eight most abundant tea catechins, gallic acid, and caffeine was developed. These
      compounds were rapidly separated within 9 min by a linear gradient elution using
      a Zorbax SB-C18 packed with sub 2 MUm particles. This methodology did not require
      preparative and semipreparative HPLC steps. In fact, diluted tea samples can be
      easily analyzed using HPLC-MS as described in this study. The use of mass
      spectrometry detection for quantification of catechins ensured a higher
      specificity of the method. The percent relative standard deviation was generally
      lower than 4 and 7% for most of the compounds tested in tea drinks and tea
      extracts, respectively. Furthermore, the method provided excellent resolution for
      folate determination alone or in combination with catechins. To date, no HPLC
      method able to discriminate catechins and folates in a quick analysis has been
      reported in the literature. 

PMID- 24734960
TI  - Investigation of variations in the acrylamide and N(epsilon) -(carboxymethyl)
      lysine contents in cookies during baking.
AB  - Baking processing is indispensable to determine special sensory prosperities of
      cookies and induces the formation of some beneficial components such as
      antioxidants. However, the formation of some Maillard reaction-derived chemical
      hazards, such as acrylamide (AA) and N(epsilon) -(carboxymethyl) lysine (CML) in
      cookies is also a significant consequence of baking processing from a food safety
      standpoint. This study investigated the effects of baking conditions on the
      formation of AA and CML, as well as the antioxidant activity (AOA) of cookies.
      Cookies were baked at various baking temperatures (155 to 230  degrees C) and
      times (1.5 to 31 min). AA and CML contents were determined by ultra-performance
      liquid chromatography-tandem mass spectrometry, respectively. The highest level
      of AA was obtained in the cookies baked at 155  degrees C/21 min and 205  degrees
      C/11 min (328.93 +/- 3.10 MUg/kg and 329.29 +/- 5.29 MUg/kg), while the highest
      level of CML was obtained in the cookies baked at 230  degrees C/1.5 min (118.05
      +/- 0.21 mg/kg). AA was prone to form at relatively low temperature range (155 to
      205  degrees C), however, CML at relatively high temperature range (205 to 230 
      degrees C). The CML content was much higher than the AA content in the same set
      of cookies, by about 2 to 3 orders of magnitude. The AOA of cookies increased at
      more severe baking conditions. According to the AA and CML content, AOA and
      sensory properties of cookies, the temperature-time regime of 180  degrees C/16
      min might be a compromised selection. However, only optimizing the baking
      condition was not enough for manufacture of high-quality cookies. PRACTICAL
      APPLICATION: Cookies, a kind of widely consumed bakery products in the world,
      contain some potentially harmful compounds, like acrylamide (AA) and N(epsilon) 
      (carboxymethyl) lysine (CML). AA in cookies has led to public health concern and
      several research efforts. But CML, another Maillard reaction-derived chemical
      hazard, has been neglected so far, even though its content is much higher than
      that of AA in cookies. The results contribute to further insight into the
      Maillard reaction and are useful for the selection of baking conditions to
      produce high-quality cookies with lower AA and CML contents, higher AOA, and
      better sensory properties.

PMID- 24734961
TI  - Preferences and decision needs of Boston-area travelers to countries with risk of
      Yellow fever virus transmission: implications for health care providers.
AB  - BACKGROUND: Yellow fever (YF), a potentially fatal mosquito-borne infection, is
      preventable with a live-attenuated vaccine, rarely associated with severe adverse
      events. We surveyed travelers to assess their reasons for pre-travel medical
      consultation, information they considered important regarding YF disease and
      vaccination, whether they recalled receiving this information, and whether they
      were involved in vaccine decision-making. METHODS: Travelers aged 18 years and
      older were surveyed at three Boston-area travel clinics. Only those making YF
      vaccination decisions were included for analyses. RESULTS: Of 831 travelers
      surveyed, 589 (70%) indicated making a YF vaccination decision. Travel medicine
      providers recommended YF vaccination to 537 (91%) of 589 travelers; 92% of these
      537 received vaccine. Among 101 travelers aged 60 years and older, 9% declined
      the vaccine; among those younger than 60 years, 4% declined the vaccine (p =
      0.06). Of 589 travelers, most agreed they needed to understand destination
      specific YF risks (82%) and vaccine risks (88%), and were involved in YF vaccine
      decisions (87%). Less than half recalled discussing their concerns about YF
      vaccine with the provider (42%) or what risks and benefits mattered most to them
      (32%). CONCLUSION: Most participants sought YF disease and vaccine risk
      information and wanted to be involved in decision-making; however, fewer than
      half recalled discussing their opinions or concerns about YF vaccine. Providers
      need effective risk communication skills and the ability to elicit and respond to
      travelers' concerns to help them make informed, shared decisions.

PMID- 24734962
TI  - Systematic analysis of reactivities and fragmentation of glutathione and its
      isomer GluCysGly.
AB  - Glutathione (GSH) is the most abundant tripeptide in human cells and plays an
      important role in protecting cells' integrity against oxidative stress. GSH has
      an unusual amide linkage formed between the gamma-carboxylic group of the
      glutamic acid in its side-chain and the amine group of cysteine residue. In the
      present study, we have compared reactivities of GSH to its isomer GluCysGly
      (ECG), which has a regular amide bond formed between the alpha-carboxylic group
      of glutamic acid and the amine group of cysteine residue. The fragmentation
      pattern of GSH ions in the gas phase is different from that of ECG ions, showing
      that the loss of H2O is the major dissociation pathway in ECG fragmentation. This
      is consistent with the dissociation pathway predicted by density functional
      calculation. Formation of GSSG from oxidation of GSH is faster than that of ECG
      disulfide, and the gas phase fragmentation pattern of GSSG is different from that
      of ECG disulfide. GSH and ECG display similar rates in nucleophilic aromatic
      substitution when reacting with 1-chloro-2,4-dinitrobenzene (CDNB). However, in
      the presence of glutathione S-transferases (GST), substitution of CDNB by GSH is
      10 times faster than that by ECG. GSH and ECG also show differences in clustering
      patterns in the gas phase. Taken together, our results shed light on
      understanding effects of unique boding structure in GSH on its stability and
      reactivities. 

PMID- 24734963
TI  - Biotransformation of trace organic contaminants in open-water unit process
      treatment wetlands.
AB  - The bottoms of shallow, open-water wetland cells are rapidly colonized by a
      biomat consisting of an assemblage of photosynthetic and heterotrophic
      microorganisms. To assess the contribution of biotransformation in this biomat to
      the overall attenuation of trace organic contaminants, transformation rates of
      test compounds measured in microcosms were compared with attenuation rates
      measured in a pilot-scale system. The biomat in the pilot-scale system was
      composed of diatoms (Staurosira construens) and a bacterial community dominated
      by beta- and gamma-Proteobacteria. Biotransformation was the dominant removal
      mechanism in the pilot-scale system for atenolol, metoprolol, and trimethoprim,
      while sulfamethoxazole and propranolol were attenuated mainly via photolysis. In
      microcosm experiments, biotransformation rates increased for metoprolol and
      propranolol when algal photosynthesis was supported by irradiation with visible
      light. Biotransformation rates increased for trimethoprim and sulfamethoxazole in
      the dark, when microbial respiration depleted dissolved oxygen concentrations
      within the biomat. During summer, atenolol, metoprolol, and propranolol were
      rapidly attenuated in the pilot-scale system (t1/2 < 0.5 d), trimethoprim and
      sulfamethoxazole were transformed more slowly (t1/2 ~ 1.5-2 d), and carbamazepine
      was recalcitrant. The combination of biotransformation and photolysis resulted in
      overall transformation rates that were 10 to 100 times faster than those
      previously measured in vegetated wetlands, allowing for over 90% attenuation of
      all compounds studied except carbamazepine within an area similar to that typical
      of existing full-scale vegetated treatment wetlands. 

PMID- 24734964
TI  - Synthesis of the first water-soluble hemicryptophane host: selective recognition
      of choline in aqueous medium.
AB  - The first water-soluble hemicryptophane cage compound, 4, was synthesized in
      seven steps from commercially available products, and its complexation properties
      were studied. NMR and ITC experiments indicate that 4 is an efficient receptor
      for choline in water (DeltaG degrees  = -5.2 kcal mol(-1)). High substrate
      selectivity was achieved since no complexation was observed for its closely
      related substrates: glycine betaine and betaine aldehyde. Density functional
      theory calculations were performed to analyze the interactions that are involved
      in the formation of the inclusion complex. 

PMID- 24734965
TI  - Cardiopulmonary effects during anaesthesia induced and maintained with propofol
      in acepromazine pre-medicated donkeys.
AB  - OBJECTIVE: To evaluate the cardiopulmonary effects of anaesthesia induced and
      maintained with propofol in acepromazine pre-medicated donkeys. STUDY DESIGN:
      Prospective experimental study. ANIMALS: Six healthy male donkeys weighing 78-144
      kg. METHODS: Donkeys were pre-medicated with intravenous (IV) acepromazine (0.04
      mg kg(-1) ). Ten minutes later, anaesthesia was induced with IV propofol (2 mg
      kg(-1) ) and anaesthesia maintained by continuous IV infusion of the propofol
      (0.2 mg kg(-1)  minute(-1) ) for 30 minutes. Baseline measurements of
      physiological parameters, and arterial blood samples were taken before the
      acepromazine administration, then 5, 15, 30, 45, and 60 minutes after the
      induction of anaesthesia. Changes from baseline were analysed by anova for
      repeated measures. RESULTS: When compared with baseline (standing) values, during
      anaesthesia heart rate increased throughout: significant at 5 (p = 0.001) and 15
      (p = 0.015) minutes. Mean arterial blood pressure increased significantly only at
      15 minutes (p < 0.001). Respiratory rate and arterial pH did not change
      significantly. PaO2 was lower throughout anaethesia, but this only reached
      significance at 15 minutes (p = 0.041). PaCO2 was statistically (but not
      clinically) significantly reduced at the times of 30 (p = 0.02), 45 (p = 0.01)
      and 60 (p = 0.04). Rectal temperature decreased significantly at all times of the
      study. CONCLUSIONS AND CLINICAL RELEVANCE: Administration of propofol by the
      continuous infusion rate for the maintenance of anaesthesia resulted in stable
      cardiopulmonary effects and could prove to be clinically useful in donkeys.

PMID- 24734966
TI  - Report of a case emphasizing the clinical utility of fine needle aspiration
      cytology in the diagnosis of histoid leprosy.

PMID- 24734967
TI  - Key issues and challenges in estimating the impact and cost-effectiveness of
      quadrivalent influenza vaccination.
AB  - Evidence has shown that quadrivalent influenza vaccines containing all four
      subtypes are safe and immunogenic. However, to date there have been few published
      studies exploring the population-level clinical and economic impact of
      quadrivalent compared to trivalent influenza vaccines. Economic evaluation
      studies need to be conducted in order to inform country-level decision making
      about whether (and how to) introduce and replace the current trivalent influenza
      vaccines with quadrivalent influenza vaccination programs. Several key issues
      associated with estimating the clinical and economic impact of the trivalent
      versus quadrivalent vaccines are discussed in this article, particularly the
      complexities involved in estimating the incremental preventable disease and
      economic burden. Other factors, such as the indirect (herd) protection from
      quadrivalent influenza vaccination and the timing of the replacement of trivalent
      influenza vaccination programs are also discussed. 

PMID- 24734968
TI  - Stimuli-responsive cement-reinforced rubber.
AB  - In this work, we report the successful development of a cement-rubber reactive
      composite with reversible mechanical properties. Initially, the composite behaves
      like rubber containing inert filler, but when exposed to water, it increases in
      volume and reaches a stiffness that is intermediate between that of hydrogenated
      nitrile butadiene rubber (HNBR) and hydrated cement, while maintaining a
      relatively large ductility characteristic of rubber. After drying, the modulus
      increases even further up to 400 MPa. Wet/drying cycles prove that the elastic
      modulus can reversibly change between 150 and 400 MPa. Utilizing attenuated total
      reflection Fourier transform infrared spectroscopy), we demonstrate that the high
      pH produced by the hydration of cement triggers the hydrolysis of the rubber
      nitrile groups into carboxylate anions. Thus, the salt bridges, generated between
      the carboxylate anions of the elastomer and the cations of the filler, are
      responsible for the reversible variations in volume and elastic modulus of the
      composite as a consequence of environmental moisture exposure. These results
      reveal that cement nanoparticles can successfully be used to accomplish a twofold
      task: (a) achieve an original postpolymerization modification that allows one to
      work with carboxylate HNBR (HXNBR) not obtained by direct copolymerization of
      carboxylate monomers with butadiene, and (b) synthesize a stimuli-responsive
      polymeric composite. This new type of material, having an ideal behavior for
      sealing application, could be used as an alternative to cement for oil field
      zonal isolation applications. 

PMID- 24734969
TI  - Cognitive conflicts in major depression: between desired change and personal
      coherence.
AB  - OBJECTIVES: The notion of intrapsychic conflict has been present in
      psychopathology for more than a century within different theoretical
      orientations. However, internal conflicts have not received enough empirical
      attention, nor has their importance in depression been fully elaborated. This
      study is based on the notion of cognitive conflict, understood as implicative
      dilemma (ID), and on a new way of identifying these conflicts by means of the
      Repertory Grid Technique. Our aim was to explore the relevance of cognitive
      conflicts among depressive patients. DESIGN: Comparison between persons with a
      diagnosis of major depressive disorder and community controls. METHODS: A total
      of 161 patients with major depression and 110 non-depressed participants were
      assessed for presence of IDs and level of symptom severity. The content of these
      cognitive conflicts was also analysed. RESULTS: Repertory grid analysis indicated
      conflict (presence of ID/s) in a greater proportion of depressive patients than
      in controls. Taking only those grids with conflict, the average number of IDs per
      person was higher in the depression group. In addition, participants with
      cognitive conflicts displayed higher symptom severity. Within the clinical
      sample, patients with IDs presented lower levels of global functioning and a more
      frequent history of suicide attempts. CONCLUSIONS: Cognitive conflicts were more
      prevalent in depressive patients and were associated with clinical severity.
      Conflict assessment at pre-therapy could aid in treatment planning to fit patient
      characteristics.

PMID- 24734970
TI  - The influence of a seated break on prolonged standing induced low back pain
      development.
AB  - With the recent attention to 'sitting disease', health practitioners and
      scientists are promoting standing in the workplace to decrease sedentary time,
      despite a high prevalence of low back pain (LBP) development during prolonged
      standing. The purpose of this study was to assess how a seated break inserted
      between bouts of prolonged standing would influence LBP development, posture and
      movement. A total of 20 participants stood for 45 minutes, sat for 15 minutes and
      repeated this sequence while lumbar and thoracic angles were measured, and LBP
      visual analogue scale reports were taken. Of the sample, 55% participants
      reported LBP in standing. A stand to sit ratio of 3:1 did not provide lasting
      recovery of LBP from standing and pain developers utilised a limited range of
      their lumbar spine angle and increased thoracic extension, resulting in static
      postures that caused tissue aggravation that was not resolved after 15 minutes of
      sitting. Prolonged standing in the workplace has the potential to result in LBP
      for some workers and alternate ways to reduce sedentary time should be
      investigated. 

PMID- 24734971
TI  - Self-selected duty cycle times for grip force, wrist flexion postures and three
      grip types.
AB  - Performance and health issues are common in industry. On-the-job productivity
      gains related to good design, which could help justify ergonomics intervention,
      are often not considered. More quantitative data are needed to model the
      discomfort/productivity relationship for upper limb activity in simulated
      repetitive assembly type work. Eighteen participants completed an experiment,
      simulating a repetitive upper limb task with force, posture and grip type
      recorded as independent variables. Duty cycle time and discomfort were recorded
      as dependent variables. Participants performed 18 experiment combinations (block
      designed around force); each treatment lasted 35 min, including breaks. Analysis
      indicated a significant two-way interaction between posture and grip type.
      Results from this experiment were used to model the effect of these variables on
      operator discomfort and performance. 

PMID- 24734972
TI  - Analytical and toxicity characterization of halo-hydroxyl-benzoquinones as stable
      halobenzoquinone disinfection byproducts in treated water.
AB  - Exposure to chlorination disinfection byproducts (DBPs) is potentially associated
      with an increased risk of bladder cancer. Four halobenzoquinones (HBQs) have been
      detected in treated drinking water and have shown potency in producing reactive
      oxygen species and inducing damage to cellular DNA and proteins. These HBQs are
      unstable in drinking water. The fate and behavior of these HBQs in drinking water
      distribution systems is unclear. Here we report the high-resolution mass
      spectrometry identification of the transformation products of HBQs as halo
      hydroxyl-benzoquinones (OH-HBQs) in water under realistic conditions. To further
      examine the kinetics of transformation, we developed a solid-phase extraction
      with ultrahigh-performance liquid chromatography tandem mass spectrometry (SPE
      UHPLC-MS/MS) method to determine both the HBQs and OH-HBQs. The method provides
      reproducible retention times (SD < 0.05 min), limits of detection (LODs) at
      subnanogram per liter levels, and recoveries of 68%-96%. Using this method, we
      confirmed that decrease of HBQs correlated with increase of OH-HBQs in both the
      laboratory experiments and several distribution systems, supporting that OH-HBQs
      were more stable forms of HBQ DBPs. To understand the toxicological relevance of
      the OH-HBQs, we studied the in vitro toxicity with CHO-K1 cells and determined
      the IC50 of HBQs and OH-HBQs ranging from 15.9 to 72.9 MUM. While HBQs are 2-fold
      more toxic than OH-HBQs, both HBQs and OH-HBQs are substantially more toxic than
      the regulated DBPs. 

PMID- 24734973
TI  - Dorzolamide cyclodextrin nanoparticle suspension eye drops and Trusopt in rabbit.
AB  - PURPOSE: Dorzolamide nanoparticle gamma-cyclodextrin eye drops may prolong the
      effect of dorzolamide on intraocular pressure. We test whether the nanoparticle
      drops have an irritating or toxic effect on the eye in an in vivo rabbit model.
      METHODS: Eighteen pigmented rabbits were divided into 4 groups receiving
      dorzolamide nanoparticle gamma-cyclodextrin eye drops*1/day or*2/day, Trusopt(r)
      (dorzolamide HCl)*3/day, and untreated controls that received no drops. The
      rabbits received treatment for 1 month. After sacrifice, 33 eyes and 25 Harderian
      glands were evaluated for histopathology in a masked way. RESULTS: Mild
      inflammation was seen in 19/31 eyes and 13/23 Harderian glands. The difference in
      inflammation (n=eyes/n=glands)between the gamma-cyclodextrin nanoparticle eye
      drops*1/day (n=5/5),*2/day (n=5/3), Trusopt (n=7/4), or untreated control (n=2/0)
      groups was nonsignificant in both eyes and glands (P=0.87 and P=0.92) Acute
      inflammation was seen in 1 Harderian gland that received gamma-cyclodextrin
      nanoparticle eye drops*2/day. The difference in conjunctival injection between
      the groups was nonsignificant (P=0.30). CONCLUSIONS: Dorzolamide gamma
      cyclodextrin nanoparticle eye drops are no more locally toxic or irritating to
      the eye than Trusopt.

PMID- 24734974
TI  - Orthodontic treatment of a patient with hypoglossia.
AB  - OBJECTIVE: The aim of this case study was to provide a detailed report of the
      orthodontic approach used in treating a Japanese patient with congenital
      hypoglossia. PATIENT: The patient was a 6-year-old girl with hypoglossia,
      micrognathia, congenital absence of three incisors, and a telescopic occlusion
      accompanied by an extremely narrow lower arch. She had no limb anomalies, and her
      speech was normal. RESULTS: Bite opening and mandibular widening from the early
      mixed dentition dramatically improved the extremely constricted mandible and
      telescopic occlusion. Cephalometric tracings taken from the beginning to the end
      of active treatment revealed substantial forward and downward growth in the
      mandible over time, which may have contributed to correction of the
      intermaxillary relationship. CONCLUSIONS: Treatment of telescopic occlusion by
      bite opening and mandibular widening from the early mixed dentition may be
      effective in facilitating mandibular growth acceleration. An acceptable
      intermaxillary occlusal relationship and improvement of profile were achieved by
      an orthodontic approach in this case.

PMID- 24734975
TI  - Rapid intraoperative fabrication of an inexpensive, reliable nasal stent for use
      after primary cleft nasal repair.
AB  - Nasal stents are frequently used to maintain corrected nostril shape following
      primary cleft lip and nasal repair. Various stents have been described, but they
      are often cumbersome to generate, expensive, or difficult to retain. The author
      describes a rapid, effective, and inexpensive alternative to previously described
      commercially available or molded nasal stents whereby a nasal stent is fabricated
      from a pediatric nasal oxygen cannula. All patients in whom this stent has been
      used to date tolerated it well with no complication and with good maintenance of
      nostril shape at a minimum of 6 months follow-up. 

PMID- 24734976
TI  - Body shape indices and cardiometabolic risk in adolescents.
AB  - BACKGROUND: "A Body Shape Index" (ABSI) is a recently proposed index that
      standardizes waist circumference for body mass index (BMI) and height using the
      scaling exponents 2/3 and 1/2, respectively, estimated from adults. Incidentally,
      waist-to-height ratio has been suggested as an indicator of cardiometabolic risk
      in adolescents. AIMS: This study aims to estimate the scaling exponents for
      standardizing waist circumference for BMI and height in Chinese adolescents and
      to estimate and compare the ability of various body shape indices in predicting
      cardiometabolic risk in adolescents. SUBJECTS AND METHODS: Participants aged 10
      17 years in the 2009 China Health and Nutrition Survey were analysed. RESULTS:
      The appropriate scaling exponents for standardizing waist circumference for BMI
      and height in this adolescent sample were 0.45 and 0.55, respectively. A new ABSI
      adolescents was defined accordingly. Ignoring the age dependence in the scaling
      exponents would lead to confounded associations. The ABSI-adolescents and the
      waist-to-height ratio were more associated with glycated haemoglobin and pre
      diabetes, but not blood pressure, than the BMI was. CONCLUSION: The scaling
      exponent for standardizing waist circumference for BMI is age-dependent. Indices
      based on waist circumference adjusted for BMI are more associated with glycated
      haemoglobin than BMI in adolescents.

PMID- 24734977
TI  - Microstructural brain changes in acromegaly: quantitative analysis by diffusion
      tensor imaging.
AB  - OBJECTIVE: We examined brain diffusion changes of patients with acromegaly. We
      searched whether there are differences in apparent diffusion coefficient (ADC)
      and fractional anisotropy (FA) values between remission and non-remission
      patients with acromegaly and investigated any effect of time of hormone exposure
      on diffusion metrics. METHODS: The values of FA and ADC were calculated in a
      total of 35 patients with acromegaly and 28 control subjects. Patients were
      subdivided into remission and non-remission groups. We looked at brain FA and ADC
      differences among the groups and looked for any relation between the diffusion
      changes and time of hormone exposure among the patients with acromegaly. RESULTS:
      We found decreased FA and increased ADC values in some of the growth hormone
      responsive areas. There were no significant brain diffusion changes between
      remission and non-remission groups. The most affected areas were the
      hypothalamus, parietal white matter and pre-motor cortex in patients with
      acromegaly. In terms of hormone exposure time among the patients with acromegaly,
      there was no effect of disease duration on brain microstructural changes.
      CONCLUSION: All patients with acromegaly showed increased brain diffusion with no
      relation to disease duration and treatment status. We suggested that in patients
      with acromegaly, brain damage had already occurred in the subclinical period
      before symptom onset. ADVANCES IN KNOWLEDGE: This study contributes to the
      understanding of the mechanisms in acromegaly.

PMID- 24734979
TI  - Colorectal resection in nonagenarians: effectiveness of laparoscopic surgery.
AB  - INTRODUCTION: The number and proportion of elderly persons in the general
      population have been increasing. Inevitably, the incidence of colorectal
      carcinoma has also increased. Although substantial evidence indicates that
      surgery is well tolerated in patients 80 years or older, studies in nonagenarians
      are not well documented. METHODS: Consecutive nonagenarians and octogenarians who
      underwent elective laparoscopic-assisted colectomy (LAC) from September 2009
      through October 2011 were studied. Data on medical history, ASA score, details of
      operations, and postoperative events were collected. RESULTS: LAC was performed
      in nine nonagenarians and seven octogenarians. There were no complications
      related to laparoscopy. No patient required conversion from LAC to an open
      procedure or died postoperatively. Peristalsis was confirmed and oral intake was
      initiated on postoperative days 2.6 and 2.7, respectively. CONCLUSIONS:
      Laparoscopic surgery is considered an extremely useful treatment for very old
      patients because it has a low risk of postoperative complications, even in the
      presence of pre-existing diseases. We conclude that LAC may be indicated in
      nonagenarians.

PMID- 24734981
TI  - Clinical leadership in mental health nursing: the importance of a calm and
      confident approach.
AB  - PURPOSE: Explore the perceptions of nurses working in mental health of effective
      clinical leadership. DESIGN AND METHODS: In-depth interviews were conducted with
      registered nurses employed in a mental health setting. Qualitative research using
      grounded theory. FINDINGS: Remaining calm and confident in times of crisis and
      uncertainty was identified as one attribute of clinical leadership. Participants
      noted clinical leaders' demeanor during stressful or crisis situations, and their
      ability to manage unpredictable or unexpected clinical situations as contributing
      positively to clinical practice. PRACTICE IMPLICATIONS: Understanding these
      characteristics and how they can influence positive outcomes for clients is
      crucial in addressing the recruitment and retention challenges for the nursing
      workforce.

PMID- 24734980
TI  - Evolution of gene structure in the conifer Picea glauca: a comparative analysis
      of the impact of intron size.
AB  - BACKGROUND: A positive relationship between genome size and intron length is
      observed across eukaryotes including Angiosperms plants, indicating a co
      evolution of genome size and gene structure. Conifers have very large genomes and
      longer introns on average than most plants, but impacts of their large genome and
      longer introns on gene structure has not be described. RESULTS: Gene structure
      was analyzed for 35 genes of Picea glauca obtained from BAC sequencing and genome
      assembly, including comparisons with A. thaliana, P. trichocarpa and Z. mays. We
      aimed to develop an understanding of impact of long introns on the structure of
      individual genes. The number and length of exons was well conserved among the
      species compared but on average, P. glauca introns were longer and genes had four
      times more intronic sequence than Arabidopsis, and 2 times more than poplar and
      maize. However, pairwise comparisons of individual genes gave variable results
      and not all contrasts were statistically significant. Genes generally accumulated
      one or a few longer introns in species with larger genomes but the position of
      long introns was variable between plant lineages. In P. glauca, highly expressed
      genes generally had more intronic sequence than tissue preferential genes.
      Comparisons with the Pinus taeda BACs and genome scaffolds showed a high
      conservation for position of long introns and for sequence of short introns. A
      survey of 1836 P. glauca genes obtained by sequence capture mostly containing
      introns <1 Kbp showed that repeated sequences were 10* more abundant in introns
      than in exons. CONCLUSION: Conifers have large amounts of intronic sequence per
      gene for seed plants due to the presence of few long introns and repetitive
      element sequences are ubiquitous in their introns. Results indicate a complex
      landscape of intron sizes and distribution across taxa and between genes with
      different expression profiles.

PMID- 24734982
TI  - The differential effects of 2% oxygen preconditioning on the subsequent
      differentiation of mouse and human pluripotent stem cells.
AB  - A major challenge facing the development of effective cell therapies is the
      efficient differentiation of pluripotent stem cells (PSCs) into pure populations.
      Lowering oxygen tension to physiological levels can affect both the expansion and
      differentiation stages. However, to date, there are no studies investigating the
      knock-on effect of culturing PSCs under low oxygen conditions on subsequent
      lineage commitment at ambient oxygen levels. PSCs were passaged three times at 2%
      O2 before allowing cells to spontaneously differentiate as embryoid bodies (EBs)
      in high oxygen (20% O2) conditions. Maintenance of mouse PSCs in low oxygen was
      associated with a significant increase in the expression of early differentiation
      markers FGF5 and Eomes, while conversely we observed decreased expression of
      these genes in human PSCs. Low oxygen preconditioning primed mouse PSCs for their
      subsequent differentiation into mesodermal and endodermal lineages, as confirmed
      by increased gene expression of Eomes, Goosecoid, Brachyury, AFP, Sox17, FoxA2,
      and protein expression of Brachyury, Eomes, Sox17, FoxA2, relative to high oxygen
      cultures. The effects extended to the subsequent formation of more mature
      mesodermal lineages. We observed significant upregulation of cardiomyocyte marker
      Nkx2.5, and critically a decrease in the number of contaminant pluripotent cells
      after 12 days using a directed cardiomyocyte protocol. However, the impact of low
      oxygen preconditioning was to prime human cells for ectodermal lineage commitment
      during subsequent EB differentiation, with significant upregulation of Nestin and
      beta3-tubulin. Our research demonstrates the importance of oxygen tension control
      during cell maintenance on the subsequent differentiation of both mouse and human
      PSCs, and highlights the differential effects. 

PMID- 24734983
TI  - Docosahexaenoic acid inhibits vascular endothelial growth factor (VEGF)-induced
      cell migration via the GPR120/PP2A/ERK1/2/eNOS signaling pathway in human
      umbilical vein endothelial cells.
AB  - Cell migration plays an important role in angiogenesis and wound repair. Vascular
      endothelial growth factor (VEGF) is an endothelial cell-specific mitogen that is
      essential for endothelial cell survival, proliferation, and migration.
      Docosahexaenoic acid (DHA), an n-3 polyunsaturated fatty acid, shows both anti
      inflammatory and antioxidant activities in vitro and in vivo. This study
      investigated the molecular mechanism by which DHA down-regulates VEGF-induced
      cell migration. HUVECs were used as the study model, and the MTT assay, Western
      blot, wound-healing assay, and phosphatase activity assay were used to explore
      the effects of DHA on cell migration. GPR120 is the putative receptor for DHA
      action. The results showed that DHA, PD98059 (an ERK1/2 inhibitor), and GW9508 (a
      GPR120 agonist) inhibited VEGF-induced cell migration. In contrast, pretreatment
      with okadaic acid (OA, a PP2A inhibitor) and S-nitroso-N-acetyl-DL-penicillamine
      (an NO donor) reversed the inhibition of cell migration by DHA. VEGF-induced cell
      migration was accompanied by phosphorylation of ERK1/2 and eNOS. Treatment of
      HUVECs with DHA increased PP2A enzyme activity and decreased VEGF-induced
      phosphorylation of ERK1/2 and eNOS. However, pretreatment with OA significantly
      decreased DHA-induced PP2A enzyme activity and reversed the DHA inhibition of
      VEGF-induced ERK1/2 and eNOS phosphorylation. These results suggest that
      stimulation of PP2A activity and inhibition of the VEGF-induced ERK1/2/eNOS
      signaling pathway may be involved in the DHA suppression of VEGF-induced cell
      migration. Thus, the effect of DHA on angiogenesis and wound repair is at least
      partly by virtue of its attenuation of cell migration.

PMID- 24734984
TI  - Corneal blindness: a global problem.

PMID- 24734985
TI  - Correcting refractive error with spectacles: a simple solution but a global
      challenge.

PMID- 24734986
TI  - Hemospray for multifocal bleeding following ultra-low rectal endoscopic
      submucosal dissection.

PMID- 24734987
TI  - Neurofunctional maps of the 'maternal brain' and the effects of oxytocin: a
      multimodal voxel-based meta-analysis.
AB  - Several studies have tried to understand the possible neurobiological basis of
      mothering. The putative involvement of oxytocin, in this regard, has been deeply
      investigated. Performing a voxel-based meta-analysis, we aimed at testing the
      hypothesis of overlapping brain activation in functional magnetic resonance
      imaging (fMRI) studies investigating the mother-infant interaction and the
      oxytocin modulation of emotional stimuli in humans. We performed two systematic
      literature searches: fMRI studies investigating the neurofunctional correlates of
      the 'maternal brain' by employing mother-infant paradigms; and fMRI studies
      employing oxytocin during emotional tasks. A unimodal voxel-based meta-analysis
      was performed on each database, whereas a multimodal voxel-based meta-analytical
      tool was adopted to assess the hypothesis that the neurofunctional effects of
      oxytocin are detected in brain areas implicated in the 'maternal brain.' We found
      greater activation in the bilateral insula extending to the inferior frontal
      gyrus, basal ganglia and thalamus during mother-infant interaction and greater
      left insular activation associated with oxytocin administration versus placebo.
      Left insula extending to basal ganglia and frontotemporal gyri as well as
      bilateral thalamus and amygdala showed consistent activation across the two
      paradigms. Right insula also showed activation across the two paradigms, and
      dorsomedial frontal cortex activation in mothers but deactivation with oxytocin.
      Significant activation in areas involved in empathy, emotion regulation,
      motivation, social cognition and theory of mind emerged from our multimodal meta
      analysis, supporting the need for further studies directly investigating the
      neurobiology of oxytocin in the mother-infant relationship. 

PMID- 24734988
TI  - White upconversion luminescence nanocrystals for the simultaneous and selective
      detection of 2,4,6-trinitrotoluene and 2,4,6-trinitrophenol.
AB  - A highly water stable and strong upconversion (UC) luminescence NaYF4@PSI-NH
      nanosensor for the simultaneous and selective detection of 2,4,6-trinitrotoluene
      (TNT) and 2,4,6-trinitrophenol (TNP) was successfully developed. Via the 980 nm
      near-infrared (NIR) irradiation, these nanosensors emit strong white UC
      luminescence with five typical emission peaks centered at 363, 455, 475, 546, and
      654 nm. The UC emission at both 363 and 546 nm was quenched by the addition of
      TNT; however, the ratio of luminescence intensity at 363 nm to 546 nm (I363/I546)
      had no change with the increase of TNT concentration. Meanwhile, only violet UC
      emission at 363 nm was dramatically quenched via the addition of TNP, and the
      I363/I546 ratio is negatively proportional to the TNP concentration in the range
      of 0.01-4.5 MUg/mL of TNP. On the other hand, the green UC emission intensity at
      546 nm is in negative proportion to the concentration of TNT. Moreover,
      cyclohexane, toluene, and other nitroaromatics (such as 2,4-dinitrotoluene (DNT)
      and nitrobenzene (NB)) have no influence on the detection. Therefore, we
      developed a facile method for the simultaneous and selective detection of TNT and
      TNP in the mixture solution of nitroaromatics independent of complicated
      instruments and sample pretreatment. 

PMID- 24734989
TI  - alpha-Ketophosphonates as ester surrogates: isothiourea-catalyzed asymmetric
      diester and lactone synthesis.
AB  - Isothiourea HBTM-2.1 catalyzes the asymmetric Michael addition/lactonization of
      aryl- and alkenylacetic acids using alpha-keto-beta,gamma-unsaturated
      phosphonates as alpha,beta-unsaturated ester surrogates, giving access to a
      diverse range of stereodefined lactones or enantioenriched functionalized
      diesters upon ring-opening. 

PMID- 24734990
TI  - Reinvestigating the reaction of 1H-pyrazol-5-amines with 4,5-dichloro-1,2,3
      dithiazolium chloride: a route to pyrazolo[3,4-c]isothiazoles and pyrazolo[3,4
      d]thiazoles.
AB  - The reaction of Appel salt 1 with 1H-pyrazol-5-amines 2 gives main products N-(4
      chloro-5H-1,2,3-dithiazol-5-ylidene)-1H-pyrazol-5-amines 3, and 6H-pyrazolo[3,4
      c]isothiazole-3-carbonitriles 5, together with several minor side products. When
      the pyrazoles are N-1 methylated, the product ratio 3:5 can be modified by
      adjusting the pH of the reaction medium: acidic conditions favor formation of the
      dithiazolylidenes 3, while basic conditions favor formation of pyrazolo[3,4
      c]isothiazoles 5. Furthermore, thermolysis of N-(4-chloro-5H-1,2,3-dithiazol-5
      ylidene)-1H-pyrazol-5-amines 3 gives 1H-pyrazolo[3,4-d]thiazole-5-carbonitriles
      4. Single crystal X-ray crystallography supports the structure of 4,6-dimethyl-6H
      pyrazolo[3,4-c]isothiazole-3-carbonitrile (5a) and helps resolve a previous
      incorrect structural assignment of 1H-pyrazolo[3,4-d]thiazole-5-carbonitriles 4. 

PMID- 24734991
TI  - Handheld mechanical nociceptive threshold testing in dairy cows - intra
      individual variation, inter-observer agreement and variation over time.
AB  - OBJECTIVE: To examine the use of handheld methodology to assess mechanical
      nociceptive threshold (MNT) on cows kept loose-housed. STUDY DESIGN: Prospective
      randomized partial cross-over experimental study. A one-factor (test day) design
      was used to evaluate MNT over time. ANIMALS: One hundred and fifteen healthy,
      loose-housed Danish Holstein cattle. METHODS: We evaluated intra-individual
      variation, inter-observer agreement and variation over time of MNT using two
      handheld devices and two stimulation sites. Mechanical, ramped stimulations were
      performed with an algometer (6.5 mm diameter steel probe, 0-10.0 kgf) or an
      electronic von Frey device (plastic tip with diameter 0.8 mm, 0-1000 gf). Each
      cow received 5-6 consecutive stimulations within a 2 * 5 cm skin area on the
      dorsal or lateral aspect of the left third metatarsus until an avoidance reaction
      occurred. We investigated the difference in precision [expressed as coefficient
      of variation (CV)] between the combinations of devices and stimulation sites. The
      inter-observer agreement and the difference in MNT between test day 1, 3, 7, 10
      and 24 were investigated for selected combinations. Data were analysed in mixed
      models and Bland-Altman as relevant. RESULTS: The CVs did not differ [range 0.34
      0.52 (p = 0.1)]. Difference between observers (95% limits) was 0.2 kgf (2.8) and
      4 gf (369) for the algometer and von Frey device, respectively. Mechanical
      nociceptive threshold increased from 361 on test day one to 495 gf on test day 24
      (p < 0.01). CONCLUSION AND CLINICAL RELEVANCE: All methods showed a high degree
      of intra-individual variation, and no combination of device and stimulation site
      showed superior precision. Mean difference between observers was low, and MNT was
      not consistent over time. Further development of the methods is required before
      they can be used in research to investigate possible relations between claw
      lesions and hyperalgesia.

PMID- 24734992
TI  - Localized drug application and sub-second voltammetric dopamine release
      measurements in a brain slice perfusion device.
AB  - The use of fast scan cyclic voltammetry (FSCV) to measure the release and uptake
      of dopamine (DA) as well as other biogenic molecules in viable brain tissue
      slices has gained popularity over the last 2 decades. Brain slices have the
      advantage of maintaining the functional three-dimensional architecture of the
      neuronal network while also allowing researchers to obtain multiple sets of
      measurements from a single animal. In this work, we describe a simple, easy-to
      fabricate perfusion device designed to focally deliver pharmacological agents to
      brain slices. The device incorporates a microfluidic channel that runs under the
      perfusion bath and a microcapillary that supplies fluid from this channel up to
      the slice. We measured electrically evoked DA release in brain slices before and
      after the administration of two dopaminergic stimulants, cocaine and GBR-12909.
      Measurements were collected at two locations, one directly over and the other 500
      MUm away from the capillary opening. Using this approach, the controlled delivery
      of drugs to a confined region of the brain slice and the application of this
      chamber to FSCV measurements, were demonstrated. Moreover, the consumption of
      drugs was reduced to tens of microliters, which is thousands of times less than
      traditional perfusion methods. We expect that this simply fabricated device will
      be useful in providing spatially resolved delivery of drugs with minimum
      consumption for voltammetric and electrophysiological studies of a variety of
      biological tissues both in vitro and ex vivo. 

PMID- 24734993
TI  - Photophysical characterization of a chromophore/water oxidation catalyst
      containing a layer-by-layer assembly on nanocrystalline TiO2 using ultrafast
      spectroscopy.
AB  - Femtosecond transient absorption spectroscopy is used to characterize the first
      photoactivation step in a chromophore/water oxidation catalyst assembly formed
      through a "layer-by-layer" approach. Assemblies incorporating both chromophores
      and catalysts are central to the function of dye-sensitized photoelectrosynthesis
      cells (DSPECs) for generating solar fuels. The chromophore, [Rua(II)](2+) =
      [Ru(pbpy)2(bpy)](2+), and water oxidation catalyst, [Rub(II)-OH2](2+) = [Ru(4,4'
      (CH2PO3H2)2bpy)(Mebimpy)(H2O)](2+), where bpy = 2,2'-bipyridine, pbpy = 4,4'
      (PO3H2)2bpy, and Mebimpy = 2,6-bis(1-methylbenzimidazol-2-yl)pyridine), are
      arranged on nanocrystalline TiO2 via phosphonate-Zr(IV) coordination linkages.
      Analysis of the transient spectra of the assembly (denoted TiO2-[Rua(II)-Zr
      Rub(II)-OH2](4+)) reveal that photoexcitation initiates electron injection, which
      is then followed by the transfer of the oxidative equivalent from the chromophore
      to the catalyst with a rate of kET = 5.9 * 10(9) s(-1) (tau = 170 ps). While the
      assembly, TiO2-[Rua(II)-Zr-Rub(II)-OH2](4+), has a near-unit efficiency for
      transfer of the oxidative equivalent to the catalyst, the overall efficiency of
      the system is only 43% due to nonproductive photoexcitation of the catalyst and
      nonunit efficiency for electron injection. The modular nature of the layer-by
      layer system allows for variation of the light-harvesting chromophore and water
      oxidation catalyst for future studies to increase the overall efficiency. 

PMID- 24734994
TI  - Combined small cell carcinoma of the lung: a case diagnosed on bronchoscopic wash
      cytology and bronchial biopsy.

PMID- 24734995
TI  - Human leucocyte antigen-Cw6 as a predictor for clinical response to ustekinumab,
      an interleukin-12/23 blocker, in Chinese patients with psoriasis: a retrospective
      analysis.
AB  - BACKGROUND: Ustekinumab, an interleukin-12/23 inhibitor, is effective in the
      treatment of psoriasis. A recent Italian study showed more favourable response to
      ustekinumab in patients with positive human leucocyte antigen (HLA)-Cw6.
      Nonetheless, there are differences in genetic susceptibility to psoriasis between
      races, and no studies have specifically assessed the candidate genetic markers in
      predicting therapy outcome in Chinese patients with psoriasis treated with
      ustekinumab. OBJECTIVES: To determine whether HLA gene polymorphisms can predict
      the response to ustekinumab in Chinese patients with psoriasis. METHODS: Sixty
      six patients with psoriasis treated with ustekinumab were included in the study,
      and the effectiveness of ustekinumab therapy was evaluated at weeks 0, 16 and 28
      by Psoriasis Area and Severity Index (PASI). RESULTS: More HLA-Cw6-positive
      patients achieved a PASI 75 response at week 4 compared with HLA-Cw6-negative
      patients (38% vs. 9%, P = 0.019). Similarly, at week 16, patients carrying the
      HLA-Cw6 allele showed a higher likelihood of achieving PASI 50, 75 and 90 than
      Cw6-negative patients, although this was not statistically significant. At week
      28, a significantly higher percentage of HLA-Cw6-positive patients maintained
      PASI 90 response compared with Cw6-negative patients (63% vs. 26%, P = 0.035).
      Further analysis of other HLA allele polymorphisms did not show significant
      associations with therapeutic response to ustekinumab. CONCLUSIONS: This
      pharmacogenetic study provides preliminary data indicating that positive HLA-Cw6
      is associated with a good response to ustekinumab treatment in Chinese patients
      with psoriasis.

PMID- 24734996
TI  - Combining ambulatory and laboratory assessment of rollator use for balance and
      mobility in neurologic rehabilitation in-patients.
AB  - PURPOSE: Despite the common use of rollators (four-wheeled walkers),
      understanding their effects on gait and balance is limited to laboratory testing
      rather than everyday use. This study evaluated the utility of an ambulatory
      assessment approach to examine balance and mobility in everyday conditions
      compared to a laboratory assessment. METHODS: Standing and walking with a
      rollator was assessed in three neurological rehabilitation in-patients under two
      conditions: (1) in laboratory (i.e. forceplate, GaitRite), and (2) while
      performing a natural walking course within and outside of the institution. An
      instrumented rollator (iWalker) was used to measure variables related to the
      balance control (e.g. upper limb kinetics), destabilizing events (e.g.
      stumbling), and environmental context. RESULTS: Two of three patients
      demonstrated greater reliance on the rollator for standing balance (2.3-5.9 times
      higher vertical loading, 72-206% increase in COP excursion) and 29-42% faster
      gait during the walking course compared to the laboratory. Importantly,
      destabilizing events (collisions, stumbling) were recorded during the walking
      course. Such events were not observed in the laboratory. CONCLUSION: This study
      illustrated a greater reliance on the rollator during challenges in everyday use
      compared to laboratory assessment and provided evidence of specific circumstances
      associated with destabilizing events that may precipitate falls in non-laboratory
      settings. Implications for Rehabilitation The value of combining laboratory and
      ambulatory assessment approaches to provide a more comprehensive profile of the
      risks and benefits of rollator use to prevent falling was studied. Patients
      demonstrated greater reliance on rollator assistive devices for standing balance
      and exhibited higher gait speeds during ambulatory assessment, compared to
      standard laboratory protocols. Repeated instances of events that may precipitate
      falls (e.g. collisions, stumbling, and unloading behaviors) were observed only
      during the ambulatory assessment. Individual challenges to balance can be used to
      identify specific training targets, assess suitability for assistive devices, and
      recommend rehabilitation goals.

PMID- 24734997
TI  - Understanding history, philanthropy and the role of WHO in provision of assistive
      technologies for hearing loss.
AB  - Philanthropy continues to play an important role in provision of hearing devices
      and is often the only alternative for the majority of those in need of these
      devices. While this leads to improved access to services it may also create
      unsustainable service delivery models. Over the past decade, World Health
      Organization (WHO) has been making consistent efforts towards promoting
      accessibility and affordability of high-quality hearing devices, especially in
      Low- and Middle-Income Countries (LMIC). WHO developed and updated the
      "Guidelines for Hearing Aids and Services in Developing Countries", in 2004. In
      2006, WHO supported the establishment of "World Wide (WW) Hearing", to promote
      hearing aid access across the globe. In the past year, WHO has renewed these
      efforts. As the first step and following a consultation on promoting access to
      hearing devices, WHO has developed a preferred product profile in order to
      facilitate the development and access of appropriate and affordable hearing aids
      for developing countries. The Convention on the Rights of Persons with
      Disabilities (article 32), calls for international collaboration to promote
      access to assistive technology including hearing devices. A coordinated global
      effort is required to promote availability and affordability of high-quality
      hearing devices. Such an undertaking requires the cooperation of all
      stakeholders: WHO, Member States, Non-Governmental Organizations (NGOs),
      philanthropists, manufacturers and users, to fulfill the international obligation
      and bring about a change in the quality of life of millions of people with
      hearing loss. IMPLICATIONS FOR REHABILITATION: Development of preferred product
      profile for hearing aids in LMICs can improve development and provision of high
      quality, affordable hearing devices. Investment made by the recipients, such as
      partial financial contribution towards the cost of device or through purchase of
      ear mould or batteries, leads to a greater sense of responsibility towards the
      device and its maintenance. Low level of awareness about hearing loss and the
      potential benefits of hearing aids contribute to the underutilization of hearing
      aids.

PMID- 24734998
TI  - Extending particle tracking capability with Delaunay triangulation.
AB  - Particle tracking, the analysis of individual moving elements in time series of
      microscopic images, enables burgeoning new applications, but there is need to
      better resolve conformation and dynamics. Here we describe the advantages of
      Delaunay triangulation to extend the capabilities of particle tracking in three
      areas: (1) discriminating irregularly shaped objects, which allows one to track
      items other than point features; (2) combining time and space to better connect
      missing frames in trajectories; and (3) identifying shape backbone. To
      demonstrate the method, specific examples are given, involving analyzing the time
      dependent molecular conformations of actin filaments and lambda-DNA. The main
      limitation of this method, shared by all other clustering techniques, is the
      difficulty to separate objects when they are very close. This can be mitigated by
      inspecting locally to remove edges that are longer than their neighbors and also
      edges that link two objects, using methods described here, so that the
      combination of Delaunay triangulation with edge removal can be robustly applied
      to processing large data sets. As common software packages, both commercial and
      open source, can construct Delaunay triangulation on command, the methods
      described in this paper are both computationally efficient and easy to implement.

PMID- 24734999
TI  - Ultrasound-guided Prolotherapy with Polydeoxyribonucleotide Sodium in
      Ischiofemoral Impingement Syndrome.
AB  - Ischiofemoral impingement syndrome is an uncommon disorder defined by hip pain
      caused by the narrowing of the space between the ischial tuberosity and lesser
      trochanter with associated entrapment of the quadratus femoris muscle. We
      effectively treated two male patients using ultrasound-guided prolotherapy with
      polydeoxyribonucleotide sodium mixed with local anesthetics. A 24-year-old male
      patient with no history of trauma or surgery complained of bilateral hip and
      groin pain; magnetic resonance imaging demonstrated slight narrowing of the
      bilateral ischiofemoral spaces with mild enhancement of the left quadratus
      femoris muscle. A 23-year-old male patient with a history of iliotibial band
      release and iliopsoas tendon release complained of left hip and groin pain;
      magnetic resonance imaging revealed swelling of the left quadratus femoris
      muscle. After the fifth treatment session of prolotherapy, the pain severity
      score using the visual analog scale was found to be minimal (0-1/10), and follow
      up magnetic resonance imaging revealed a slightly decreased enhancement of the
      quadratus femoris muscle compared with that on previous images. Prolotherapy with
      polydeoxyribonucleotide sodium was an efficacious treatment for two patients with
      ischiofemoral impingement syndrome who were not candidates for surgery. 

PMID- 24735000
TI  - Interpreting cobalt blood concentrations in hip implant patients - let us not,
      yet, skip the uncertainty factor.

PMID- 24735001
TI  - Prolonged altered mental status and bradycardia following pediatric donepezil
      ingestion.
AB  - CONTEXT: Donepezil is a centrally-acting, reversible acetylcholinesterase
      inhibitor that is used in the treatment of Alzheimer disease. Altered mental
      status, nausea, vomiting, and bradycardia have been reported in therapeutic and
      supratherapeutic ingestions of donepezil, though pediatric exposures have not
      been well-described. We report a case of prolonged altered mental status and
      recurrent bradycardia in a child with a single-pill ingestion of donepezil. CASE
      DETAILS: A 14-month-old boy was brought to the Emergency Department 3 hours after
      ingesting one of his grandfather's donepezil tablets (10 mg). Upon arrival, he
      was somnolent and drooling, with multiple episodes of vomiting and diarrhea.
      Pupils were normal. Initial vitals: temperature, 36.8 degrees C; blood pressure,
      103/56 mmHg; heart rate, 140/min; respiratory rate, 36/min; oxygen saturation,
      97%. His drooling, vomiting, and diarrhea resolved, but he remained
      intermittently agitated. Over the course of the following four days, he had
      intermittent, episodes of asymptomatic bradycardia to a low of 55/min, primarily
      when sleeping. A transient episode of junctional rhythm was observed. Serum
      donepezil level 97 hours post-ingestion was 10 ng/ml. He did not require atropine
      treatment, and was discharged in stable condition on hospital day 5. DISCUSSION:
      Donepezil has a prolonged elimination of half-life in adults of approximately 70
      hours. Despite its relative specificity for central AChEs, peripheral cholinergic
      symptoms have been described. We report a case of a symptomatic ingestion of
      donepezil in a child. CONCLUSIONS: Even after a single-tablet ingestion,
      donepezil may cause prolonged altered mental status and bradycardia in young
      children.

PMID- 24735002
TI  - Prevention of adverse drug events.

PMID- 24735003
TI  - National toxicovigilance for pesticide exposures resulting in health care contact
      - An example from the UK's National Poisons Information Service.
AB  - BACKGROUND: Although there are extensive systems in place for pharmacovigilance,
      similar systems for detecting adverse health effects relating to pesticide
      exposure are rare. In 2004, the National Poisons Information Service (NPIS)
      pesticide surveillance study was implemented to identify cases requiring health
      care contact in the UK. This report describes the epidemiology of pesticide
      exposures reported to poison centres in the UK over a 9-year period. METHODS:
      Data on exposures were gathered through monitoring access to the NPIS's online
      clinical toxicology database TOXBASE((r)) and through monitoring calls to the
      four NPIS units (Edinburgh, Cardiff, Newcastle and Birmingham). Severity was
      judged by both caller and NPIS staff. RESULTS: During the 9 years, 34,092
      enquiries concerning pesticides were recorded; 7,804 cases of pesticide exposure
      were derived from these enquiries. Exposures were predominantly unintentional and
      acute (6,789; 87.0%); 217 (2.8%) and 755 (9.7%) were chronic unintentional and
      acute deliberate self-harm exposures, respectively. The majority of cases
      occurred in children, especially the 0-4 year age group The minimum incidence of
      pesticide exposure requiring health care contact was 2.0 cases/100,000 population
      per year. Reported numbers were 6- to 25-fold greater than those picked up
      through other UK pesticide toxicovigilance schemes. There were 81 cases of severe
      toxicity and 38 cases of fatal exposure. Deliberate self-harm accounted for 62.3%
      of severe cases and 79% of deaths. Aluminium phosphide, paraquat, diquat and
      glyphosate were responsible for most severe and fatal cases. CONCLUSIONS: The
      data gathered from this pesticide surveillance study indicate that poison centre
      resources can usefully monitor pesticide exposures resulting in health care
      contact in the UK. The NPIS may usefully be one component of the UK's response to
      European legislation requiring surveillance of complications resulting from
      pesticide use.

PMID- 24735004
TI  - Development and implementation of a workshop to enhance the effectiveness of
      mentors working with diverse mentees in HIV research.
AB  - Abstract A growing body of evidence highlights the importance of competent
      mentoring in academic research in the field of HIV, particularly for early stage
      investigators from diverse, underrepresented backgrounds. We describe the
      development and implementation of a 2-day intensive workshop to train mid-level
      and senior-level investigators conducting HIV-related clinical and translational
      research across multiple academic institutions on more effective mentoring, with
      an emphasis on techniques to foster mentees of diversity. The workshop was
      focused on training mentors in techniques designed to improve the effectiveness
      of the mentor-mentee relationship, and included didactic presentations,
      interactive discussions, and small-group problem-based learning activities. Mid
      level or senior-level faculty involved or planning to be involved in significant
      mentorship activities related to HIV research were eligible. Surveys and formal
      actions plans allowed for workshop evaluation and laid the groundwork for
      subsequent workshops. Twenty-six faculty from 16 U.S.-based institutions
      participated, with good representation across discipline, gender, and
      race/ethnicity. The sessions were highly rated and discussions and evaluations
      revealed important barriers and facilitators to mentoring, challenges and
      solutions related to mentoring mentees from diverse backgrounds, and specific
      tools to enhance mentoring effectiveness. The Mentoring the Mentors training
      program for HIV researchers focusing on early career investigators of diversity
      was the first of its kind and was well attended, was rated highly, and provided
      guidance for improving the program in the future. This training program fills an
      important gap in the HIV researcher community and offers guidance for training
      mentors interested in diversity issues in settings outside of HIV. 

PMID- 24735005
TI  - Prophylactic use of ketorolac tromethamine in cataract surgery: a randomized
      trial.
AB  - PURPOSE: To determine the efficacy of topical ketorolac tromethamine in
      preventing cystoid macular edema (CME) after uncomplicated cataract surgery.
      METHODS: This single-center, prospective, double-masked, randomized clinical
      trial consisted of 81 patients who were scheduled for cataract surgery. Patients
      were randomized to receive hypromellose/dextran 70 as a placebo (n=44) or
      ketorolac tromethamine 0.4% (n=37) as an adjuvant therapy. These eye drops were
      administered 4 times daily (QID) for 3 days before surgery and 5 weeks
      postoperatively. All patients received prednisolone acetate 1% QID during the
      same period as basal/standard anti-inflammatory therapy. The primary outcome was
      the incidence of angiographic CME 5 weeks after surgery. The secondary outcomes
      were mean change in best-corrected visual acuity (BCVA) [Early Treatment Diabetic
      Retinopathy study (ETDRS)], clinical CME incidence, intraocular pressure, and
      retinal thickness measured using optical coherence tomography (OCT). RESULTS: In
      the placebo group, 2/44 (4.5%) patients and in the ketorolac group, 2/37 (5.4%)
      patients presented with angiographic CME (P=0.624). The mean change in
      postoperative BCVA was 32+/-15 letters in the placebo group and 26+/-16 letters
      in the ketorolac group (P=0.07). There were no statistically significant between
      group differences in the mean central subfield thickness (P=0.679), minimal
      central thickness (P=0.352), or central macular volume (P=0.729). CONCLUSION:
      There was no difference between ketorolac tromethamine and a placebo with regard
      to BCVA results or prevention of CME after uncomplicated cataract surgery.

PMID- 24735006
TI  - Serial measurements of the Nt-ProBNP during the dry state in patients with
      systolic heart failure are predictors of the long-term prognosis.
AB  - OBJECTIVE: To evaluate the long-term predictive value of serial Nt-ProBNP during
      dry-state in patients with systolic heart failure (SHF). METHODS: Nt-ProBNP was
      measured quarterly during a 6-month dry-state period in 40 SHF outpatients.
      EVENTS: all-cause mortality or hospitalization. FOLLOW-UP: 5 years. RESULTS: The
      Nt-ProBNP >1000 pg/ml (baseline and 6 months) and the variation rate (VR) >30%
      were independently associated with the survival and composite endpoint curve. VR
      >30% added significant prognostic information to the single Nt-ProBNP 1000 pg/ml
      cut-off. Patients with at least one Nt-ProBNP determination >1000 pg/ml were at
      greater risk of death. CONCLUSION: Serial Nt-ProBNP measurements in patients with
      SHF during the dry-state are strong predictors of the long-term prognosis.

PMID- 24735008
TI  - Effects and feasibility of the "traffic light method for somatic screening and
      lifestyle" in patients with severe mental illness: a pilot study.
AB  - PURPOSE: To study the preliminary effects and feasibility of the "Traffic Light
      Method for somatic screening and lifestyle" (TLM) in patients with severe mental
      illness. DESIGN AND METHODS: A pilot study using a quasi-experimental mixed
      method design with additional content analyses of lifestyle plans and logbooks.
      FINDINGS: Significant improvements were found in body weight and waist
      circumference. Positive trends were found in patients' subjective evaluations of
      the TLM. The implementation of the TLM was considered feasible. PRACTICE
      IMPLICATIONS: The TLM may contribute to a higher quality of care regarding
      somatic screening and lifestyle training.

PMID- 24735010
TI  - Human dietary exposure to PBDEs around E-waste recycling sites in Eastern China.
AB  - Analysis of 10 types of locally produced staple foods (including meat, fish, and
      eggs), provided estimates of dietary intakes of polybrominated diphenyl ethers
      (PBDEs) for residents of areas of Taizhou City (Zhejiang Province, Eastern
      China), which are long-established centers of rudimentary "e-waste" recycling.
      Average ?PBDE concentrations in chicken meat, eggs, and liver and duck meat and
      liver were among the highest recorded to date, with BDE-209 particularly
      abundant. The highest estimated contributions to ?PBDE intake under a median
      exposure scenario were associated with adult consumption of duck eggs (3882
      ng/day) and chicken eggs (1091 ng/day), and with consumption of fish by both
      adults (792 ng/day) and children (634 ng/day). Including estimates for ingestion
      of contaminated dust reported elsewhere increased median ?PBDE daily intakes by
      approximately 19% for adults and 42% for children. Normalized to body weight,
      estimated median ?PBDE exposures (from food and dust combined) were 130.9 ng/kg
      bw/day for adults and 614.1 ng/kg bw/day for children. High-end estimates of
      exposure for young children exceeded the U.S. Environmental Protection Agency
      reference doses for BDE-47 and BDE-99 by factors of approximately 2.5 and 1.5,
      respectively. 

PMID- 24735007
TI  - Gender-dependent associations between socioeconomic status and metabolic
      syndrome: a cross-sectional study in the adult Saudi population.
AB  - BACKGROUND: To determine the gender-dependent association of socio-economic
      status variables with the prevalence of metabolic syndrome (MetS) in the adult
      Saudi population. METHODS: A total of 9164 adult Saudis (aged 18-70 years) were
      included in this cross-sectional study. Marital status, income, education, and
      occupation were used as socio-economic indicators while behavioral factor like
      physical exercise was also taken into account. MetS was defined using the
      criteria based from the National Cholesterol Education Program Adult Treatment
      Panel III (NCEP-ATP III). RESULTS: In males, the odds ratio (OR) of harboring
      MetS was higher in married [OR1.6 (Confidence Interval (CI) 1.1, 2.4); p < 0.03],
      and high income class [OR 2.3(CI 1.5, 3.5); p < 0.001] and lowest in retired and
      unemployed individuals [1.4(1.0, 1.9); p < 0.04, 0.61(0.45, 0.82); p < 0.001]
      respectively. In females, MetS was inversely related to high income [OR 0.70 (CI
      0.46, 1.1); p < 0.09] and education level [OR 0.38 (CI 0.26, 0.56); p < 0.001],
      and was significantly higher in the unemployed class [OR 1.6 (CI 1.2, 2.2); p <
      0.004]. CONCLUSIONS: The prevalence of MetS is significantly high among retired,
      married and high-earning Saudi males while in females, high earners and high
      education seem to confer a protective effect against MetS.

PMID- 24735011
TI  - Risk factors for open-angle glaucoma with normal baseline intraocular pressure in
      a young population: the Korea National Health and Nutrition Examination Survey.
AB  - BACKGROUND: To identify risk factors associated with open-angle glaucoma with
      normal baseline intraocular pressure in a young Korean population. DESIGN:
      Retrospective, population-based, case-control study. PARTICIPANTS: Between 2009
      and 2010, among participants from the Korea National Health and Nutrition
      Examination Survey (n = 17 901), subjects between 19 and 39 years of age were
      included. METHODS: Participants had structured interviews systemic and ophthalmic
      examination. Glaucoma was diagnosed using the International Society of
      Geographical and Epidemiological Ophthalmology criteria. MAIN OUTCOME MEASURES:
      The risk factors for open-angle glaucoma with normal baseline intraocular
      pressure were analyzed using univariate and multivariate comparisons. RESULTS:
      Eighty open-angle glaucoma with normal baseline intraocular pressure patients and
      4015 controls were included. In the univariate analysis, the patient group was
      more likely to have higher fasting plasma glucose (98.04 +/- 33.16 vs. 89.74 +/-
      12.65, P < 0.001) and higher proportion of fasting capillary glucose >=200 mg/dL
      (P < 0.001) than the control. Multivariate analysis found that high myopia (odds
      ratio, 3.54 [95% confidence interval, 1.34-9.39], P = 0.011), fasting capillary
      glucose >=200 mg/dL (odds ratio, 12.65 [95% confidence interval, 2.63-60.94], P =
      0.002) and low high-density lipoprotein cholesterol (odds ratio, 0.96 [95%
      confidence interval, 0.94-0.99], P = 0.015) were associated with an increased
      risk of having open-angle glaucoma with normal baseline intraocular pressure.
      CONCLUSIONS: High myopia, fasting capillary glucose level >=200 mmol/L and high
      density lipoprotein cholesterol level were significant risk factors for open
      angle glaucoma with normal baseline intraocular pressure in a young Korean
      population.

PMID- 24735012
TI  - Metabolomic analysis of antimicrobial mechanisms of epsilon-poly-L-lysine on
      Saccharomyces cerevisiae.
AB  - epsilon-Poly-L-lysine (epsilon-PL), a naturally occurring amino acid homopolymer,
      has been widely used as a food preservative. However, its antimicrobial mechanism
      has not been fully understood. This study investigated the antimicrobial mode of
      action of epsilon-PL on a yeast, Saccharomyces cerevisiae. When treated with
      epsilon-PL at the concentration of 500 MUg/mL, cell mortality was close to 100%
      and the phospholipid bilayer curvature, pores, and micelles on the surface of S.
      cerevisiae were clearly observed by scanning electron microscopy (SEM). At the
      level of 200 MUg/mL, epsilon-PL significantly inhibited the cell growth of S.
      cerevisiae. When treated with 50 MUg/mL epsilon-PL, the yeast cell was able to
      grow but the cell cycle was prolonged. A significant increase in cell membrane
      permeability was induced by epsilon-PL at higher concentrations. Metabolomics
      analysis revealed that the epsilon-PL stress led to the inhibition of primary
      metabolic pathways through the suppression of the tricarboxylic acid cycle and
      glycolysis. It is therefore proposed that the microbiostatic effect of epsilon-PL
      at lower levels on S. cerevisiae is achieved by inducing intracellular metabolic
      imbalance via disruption of cell membrane functions. Moreover, the results
      suggested that the antimicrobial mechanism of epsilon-PL on S. cerevisiae can in
      fact change from microbiostatic to microbicidal when the concentration of epsilon
      PL increased, and the mechanisms of these two modes of action were completely
      different.

PMID- 24735013
TI  - Cystomanamides: structure and biosynthetic pathway of a family of glycosylated
      lipopeptides from myxobacteria.
AB  - Cystomanamides A-D were isolated as novel natural product scaffolds from
      Cystobacter fuscus MCy9118, and their structures were established by
      spectroscopic techniques including 2D NMR, LC-SPE-NMR/-MS, and HR-MS. The
      cystomanamides contain beta-hydroxy amino acids along with 3-amino-9
      methyldecanoic acid that is N-glycosylated in cystomanamide C and D. The gene
      cluster for cystomanamide biosynthesis was identified by gene disruption as
      PKS/NRPS hybrid incorporating an iso-fatty acid as starter unit and including a
      reductive amination step at the interface of the PKS and NRPS modules. 

PMID- 24735014
TI  - A peculiar histopathological form of dysembryoplastic neuroepithelial tumor with
      separated pilocytic astrocytoma and rosette-forming glioneuronal tumor
      components.
AB  - Dysembryoplastic neuroepithelial tumors (DNTs) mostly display typical clinical,
      neuroimaging and histopathological features, but sometimes they reveal
      heterogeneous or non-specific morphology, which results in diagnostic dilemmas.
      We present a case of a young adult with longstanding, intractable epilepsy
      associated with a multinodular cystic lesion in the temporal lobe. The lesion
      consisted of morphologically different components. In particular, a few cortical
      nodules displayed a specific glioneuronal element with floating neurons typically
      found in DNT. Two large, well-circumscribed nodules were entirely composed of
      biphasic, piloid, astroglial patterns that corresponded strictly to a pilocytic
      astrocytoma. The well-defined areas, which contained numerous distinct neurocytic
      like rosettes, were identical with rosette-forming glioneuronal tumors (RGNTs).
      This type of neurocytic rosette was widespread within the surrounding piloid
      background. Some solid nodules exhibited increased cellularity, oligodendroglioma
      like elements and a focal ribbon cell arrangement. The lesion was associated with
      advanced reactive gliosis and foci of dysplastic changes in the adjacent cortex.
      The clinico-radiological and main histopathological features were consistent with
      a diagnosis of a complex variant of DNT composed of pilocytic and rosette-forming
      glioneuronal components. Although both piloid tissue and rosette-like formations
      have been occasionally mentioned in DNT lesions, the present case of DNT was
      unique in its well-circumscribed, separate pilocytic and RGNT nodules. We
      concluded that it represented an unusual, mixed pilocytic/RGNT variant of DNT. 

PMID- 24735015
TI  - Sudden hearing loss followed by deep vein thrombosis and pulmonary embolism in a
      patient with factor V Leiden mutation.
AB  - OBJECTIVE: Factor V Leiden (FVL) is by far the most prevalent inherited
      thrombophilic abnormality in Western countries, and this genetic condition has
      been associated with sudden sensorineural hearing loss (SSHL). Audiologists
      should be aware that SSHL may be the precursor of life-threatening thromboembolic
      events, especially in Caucasians who are more likely to be FVL carriers. DESIGN:
      Case report. STUDY SAMPLE: A 41-year-old male patient. RESULTS: Although this is
      not the first report of SSHL in a FVL carrier, it is the first to describe SSHL
      occurring in a heterozygous FVL carrier who--within a month--was also diagnosed
      with deep vein thrombosis of the left common femoral, saphenous, and popliteal
      veins, and pulmonary embolism of the left pulmonary artery branch serving the
      posterior basal segment of the inferior lobe. CONCLUSIONS: SSHL is an emergency
      condition that warrants prompt medical examination and treatment. Hematological
      investigations should be considered in SSHL patients at least for those with a
      family history of thrombotic events, and for women on estrogen-progestin therapy
      or during pregnancy, with a view to providing adequate antithrombotic prophylaxis
      and reducing the risk of other thromboembolic events.

PMID- 24735016
TI  - Minimal residual disease monitoring in chronic lymphocytic leukaemia patients. A
      comparative analysis of flow cytometry and ASO IgH RQ-PCR.
AB  - Minimal residual disease (MRD) is becoming increasingly important in chronic
      lymphocytic leukaemia (CLL) as treatment strategies are progressively improving.
      The primary objective of this study was to compare the applicability of three
      different flow cytometric approaches: basic 4-colour analysis, European Research
      Initiative in CLL (ERIC) consensus method and 8-colour analysis. Secondly, we
      investigated the sensitivity and specificity of flow cytometry (FC) compared to
      molecular analyses for MRD detection. A total of 462 CLL samples were evaluated
      by basic FC; in 143, ERIC consensus method was also performed and all three FC
      methodologies were applied in a subgroup of 10 cases. No discordance in defining
      MRD-positive/negative samples was observed between the FC methods; within
      positive samples, the ERIC consensus method and 8-colour analysis showed the most
      accurate results. MRD was analysed by FC and polymerase chain reaction (PCR) in
      243 cases: concordant results were obtained in 199/243 samples (81.9%); 42/243
      were FC-/PCR+. Overall, the sensitivity and specificity of FC compared to PCR was
      96.5% and 77.2%, respectively. Both FC and PCR proved suitable for the detection
      of MRD and prediction of progression-free survival, which was significantly
      reduced in MRD-positive patients, regardless of the methodology. These results
      offer the rationale for a strategy to monitor MRD in CLL patients. 

PMID- 24735017
TI  - Molecular dynamics simulations and electronic excited state properties of a self
      assembled peptide amphiphile nanofiber with metalloporphyrin arrays.
AB  - We have employed molecular dynamics simulations and quantum chemistry methods to
      study the structures and electronic absorption properties of a novel type of
      photonic nanowire gel constructed by the self-assembly of peptide amphiphiles
      (PAs) and the chromophore-(PPIX)Zn molecules. Using molecular dynamics
      simulations, structures of the self-assembled fiber were determined with
      atomistic detail, including the distribution of chromophores along the nanofiber
      and the relative distances and orientations of pairs of chromophores. In
      addition, quantum chemistry calculations were used to determine the electronic
      structure and absorption properties of the chromophores in the fiber, so as to
      assess the capabilities of the nanofiber for photonics applications. The
      calculations show that the PA nanofiber provides an effective scaffold for the
      chromophores in which the chromophores form several clusters in which nearest
      neighbor chromophores are separated by less than 20 A. The calculations also
      indicate that the chromophores can be in both the hydrophilic shell and
      hydrophobic core portions of the fiber. There are only small spectral shifts to
      the B-band of the porphyrins arising from the inhomogeneous microelectronic
      environment provided by the fiber. However, there are much stronger electronic
      interactions between nearby pairs of chromophores, leading to a more significant
      red shift of the B-band that is similar to what is found in the experiments and
      to significant excitonic coupling that is seen in circular dichroism spectra.
      This electronic interaction between chromophores associated with the PA nanofiber
      structure is crucial to future applications of these fibers for light-harvesting
      applications. 

PMID- 24735018
TI  - Utility of transesophageal electrocardiography to guide optimal placement of a
      transesophageal pacing catheter in dogs.
AB  - OBJECTIVE: To determine if the transesophageal atrial (A) wave amplitude or
      ventricular (V) wave amplitude can be used to guide optimal positioning of a
      transesophageal pacing catheter in dogs. STUDY DESIGN: Prospective clinical
      study. ANIMALS: Fourteen client owned healthy dogs with a median weight of 15.4
      kg (IQR = 10.6-22.4) and a median age of 12 months (IQR = 6-12). MATERIALS AND
      METHODS: Transesophageal atrial pacing (TAP) using a 6 Fr pacing catheter was
      attempted in dogs under general anesthesia. The pacing catheter was inserted
      orally into the esophagus to a position caudal to the heart. With the pulse
      generator set at a rate 20 beats/minute(-1) above the intrinsic sinus rate, the
      catheter was slowly withdrawn until atrial pacing was noted on a surface
      electrocardiogram (ECG). Then the catheter was withdrawn in 1 cm increments until
      atrial capture was lost. Minimum pacing threshold (MPT) and transesophageal ECG
      were recorded at each site. Amplitudes of the A and V waves on transesophageal
      ECG were then measured and their relationship to MPT was evaluated. RESULTS: TAP
      was achieved in all dogs. In 9/14 dogs the site of lowest overall MPT was the
      same as the site of maximal A wave deflection. In dogs with at least three data
      points, linear regression analysis of the relationship between the estimated site
      of the lowest overall MPT compared to estimated site of the maximal A and V
      waveform amplitudes demonstrated a strong correlation (R(2) = 0.99). CONCLUSION
      AND CLINICAL RELEVANCE: Transesophageal ECG A and V waveforms were correlated to
      MPT and could be used to direct the placement of a pacing catheter. However, the
      technique was technically challenging and was not considered to be clinically
      useful to guide the placement of a pacing catheter.

PMID- 24735019
TI  - Development of pharmacophore similarity-based quantitative activity hypothesis
      and its applicability domain: applied on a diverse data-set of HIV-1 integrase
      inhibitors.
AB  - Quantitative pharmacophore hypothesis combines the 3D spatial arrangement of
      pharmacophore features with biological activities of the ligand data-set and
      predicts the activities of geometrically and/or pharmacophoric similar ligands.
      Most pharmacophore discovery programs face difficulties in conformational
      flexibility, molecular alignment, pharmacophore features sampling, and feature
      selection to score models if the data-set constitutes diverse ligands. Towards
      this focus, we describe a ligand-based computational procedure to introduce
      flexibility in aligning the small molecules and generating a pharmacophore
      hypothesis without geometrical constraints to define pharmacophore space,
      enriched with chemical features necessary to elucidate common pharmacophore
      hypotheses (CPHs). Maximal common substructure (MCS)-based alignment method was
      adopted to guide the alignment of carbon molecules, deciphered the MCS atom
      connectivity to cluster molecules in bins and subsequently, calculated the
      pharmacophore similarity matrix with the bin-specific reference molecules. After
      alignment, the carbon molecules were enriched with original atoms in their
      respective positions and conventional pharmacophore features were perceived.
      Distance-based pharmacophoric descriptors were enumerated by computing the
      interdistance between perceived features and MCS-aligned 'centroid' position. The
      descriptor set and biological activities were used to develop support vector
      machine models to predict the activities of the external test set. Finally,
      fitness score was estimated based on pharmacophore similarity with its bin
      specific reference molecules to recognize the best and poor alignments and, also
      with each reference molecule to predict outliers of the quantitative hypothesis
      model. We applied this procedure to a diverse data-set of 40 HIV-1 integrase
      inhibitors and discussed its effectiveness with the reported CPH model. 

PMID- 24735020
TI  - Single-subject gray matter graph properties and their relationship with cognitive
      impairment in early- and late-onset Alzheimer's disease.
AB  - Abstract We investigated the relationships between gray matter graph properties
      and cognitive impairment in a sample of 215 patients with Alzheimer's disease
      (AD) and also whether age of disease onset modifies such relationships. We
      expected that more severe cognitive impairment in AD would be related to more
      random graph topologies. Single-subject gray matter graphs were constructed from
      T1-weighted magnetic resonance imaging scans. The following global and local
      graph properties were calculated: betweenness centrality, normalized clustering
      coefficient gamma, and normalized path length lambda. Local clustering, path
      length, and betweenness centrality measures were determined for 90 anatomically
      defined areas. Regression models with as interaction term age of onset (i.e.,
      early onset when patients were <=65 years old and late onset when they were >65
      years old at the time of diagnosis)*graph property were used to assess the
      relationships between cognitive functioning in five domains (memory, language,
      visuospatial, attention, and executive). Worse cognitive impairment was
      associated with more random graphs, as indicated by low gamma, lambda, and
      betweenness centrality values. Three interaction effects for age of onset*global
      graph property were found: Low gamma and lambda values more strongly related to
      memory impairment in early-onset patients; low beta values were significantly
      related to impaired visuospatial functioning in late-onset patients. For the
      local graph properties, language impairment showed the strongest relationship
      with decreased clustering coefficient in the left superior temporal gyrus across
      the entire sample. Our study shows that single-subject gray matter graph
      properties are associated with individual differences in cognitive impairment. 

PMID- 24735021
TI  - Potential role of anticonvulsants in the treatment of obsessive-compulsive and
      related disorders.
AB  - We reviewed the extant literature to evaluate the current evidence regarding the
      efficacy and safety of anticonvulsants in the treatment of obsessive-compulsive
      and related disorders. Relevant literature was accessed using the Cochrane
      database, embase and PubMed on 29 October 2013. Prospective studies examining the
      efficacy of anticonvulsants in obsessive-compulsive and related disorders were
      included. Case reports, case series, and retrospective studies were excluded. A
      total of 10 studies were included in this review. The studies of obsessive
      compulsive disorder, except for two negative studies, showed favorable efficacy
      results of anticonvulsants. In one study on body dysmorphic disorder,
      levetiracetam showed favorable efficacy. In two lamotrigine studies for
      pathologic skin-picking, the efficacy findings were inconsistent. In one
      trichotillomania study, topiramate had reduced hair-pulling symptoms. Despite
      limited evidence, our review suggests that anticonvulsants have a potential role
      in the treatment of obsessive-compulsive and related disorders. 

PMID- 24735022
TI  - An efficient synthesis of bis-1,3-(3'-aryl-N-heterocycl-1'-yl)arenes as CCC-NHC
      pincer ligand precursors.
AB  - A report that demonstrated an efficient methodology for the arylation of
      imidazoles has been extended to bis(N-heterocyclic) compounds. Using bis(aryl)
      iodonium salts provides high-yielding access to CCC-NHC ligand precursors in a
      single step. Examples of arylation using various iodonium salts are reported
      herein with an investigation into the factors governing their relative rate of
      reactivity. The metalation of one of these compounds using Zr(NMe2)4 and its
      subsequent treatment with [Pt(COD)Cl2] to yield a transmetalated product are
      reported. 

PMID- 24735023
TI  - High tricellulin expression is associated with better survival in human
      hepatoblastoma.
AB  - AIMS: The more differentiated fetal component of hepatoblastoma (HB) is
      characterized by increased expression of tight junction (TJ) proteins claudin-1
      and -2 when compared with embryonal component. Expression patterns of the
      recently identified TJ protein tricellulin and the epigenetic regulator enzyme
      EZH2 were investigated in epithelial subtypes of HB and related to survival.
      METHODS AND RESULTS: Twenty-one cases of epithelial HBs subtyped as pure fetal (n
      = 12) and embryonal/fetal (n = 9), along with 16 non-tumorous samples from
      surrounding liver, were analysed by immunohistochemistry for tricellulin, beta
      catenin and EZH2 expression. No significant differences were revealed in overall
      survival between fetal and embryonal/fetal types of HBs. The fetal component,
      however, showed considerably increased tricellulin expression while the embryonal
      component displayed significantly increased nuclear EZH2 positivity, in
      comparison to other epithelial subtypes and non-tumorous surrounding hepatocytes.
      Strong nuclear beta-catenin staining was notably more frequent in embryonal than
      in fetal types. High tricellulin expression was associated with significantly
      increased overall survival (P = 0.03), while elevated EZH2 expression was linked
      to the presence of distant metastases (P = 0.013). CONCLUSIONS: Our data indicate
      that patients with treated HBs showing high expression of tricellulin have
      significantly better overall survival, independent of histological subtype.
      Increased nuclear expression of EZH2 was associated with the presence of distant
      metastases.

PMID- 24735024
TI  - Efficacy of dignity therapy on depression and anxiety in Portuguese terminally
      ill patients: a phase II randomized controlled trial.
AB  - BACKGROUND: Dignity therapy is a brief psychotherapy developed for patients
      living with a life-limiting illness. OBJECTIVE: To determine the influence of
      dignity therapy on depression and anxiety in inpatients with a terminal illness
      and experiencing a high level of distress in a palliative care unit. METHODS: A
      nonblinded phase II randomized controlled trial of 80 patients who were randomly
      assigned to one of two groups: intervention group (dignity therapy+standard
      palliative care [SPC]) or control group (SPC alone). The main outcomes were
      depression and anxiety scores, as measured with the Hospital Anxiety and
      Depression Scale, and assessed at baseline (T1), day 4 (T2), day 15 (T3), and day
      30 (T4) of follow-up. This study is registered with www.controlled
      trials.com/ISRCTN34354086. RESULTS: Of the final 80 participants, 41 were
      randomly assigned to SPC and 39 to dignity therapy. Baseline characteristics were
      similar between the two groups. Dignity therapy was associated with a decrease in
      depression scores (median, 95% confidence interval [CI]: -4.00, -6.00 to -2.00,
      p<0.0001; -4.00, -7.00 to -1.00, p=0.010; -5.00, -8.00 to -1.00, p=0.043, for T2,
      T3, and T4, respectively). Dignity therapy was similarly associated with a
      decrease in anxiety scores (median, 95% CI: -3.00, -5.00 to -1.00, p<0.0001; 
      4.00, -7.00 to -2.00, p=0.001; -4.00, -7.00 to -1.00, p=0.013, for T2, T3, and
      T4, respectively). CONCLUSION: Dignity therapy resulted in a beneficial effect on
      depression and anxiety symptoms in end-of-life care. The therapeutic benefit of
      dignity therapy was sustained over a 30-day period. Having established its
      efficacy, future trials of dignity therapy may now begin, comparing it with other
      psychotherapeutic approaches within the context of terminal illness.

PMID- 24735026
TI  - Understanding and improving clinical trial outcome measures in acute respiratory
      failure.

PMID- 24735027
TI  - Oxidant-mediated aggregation of Z alpha1-antitrypsin in pulmonary epithelial
      cells amplifies lung inflammation.

PMID- 24735028
TI  - Novel biomarkers to anticipate acute kidney injury. Getting ahead of the curve.

PMID- 24735029
TI  - Ventilator-associated complications, ventilator-associated pneumonia, and
      Newton's third law of mechanics.

PMID- 24735030
TI  - Seeing is believing: imaging early lung disease in cystic fibrosis.

PMID- 24735031
TI  - Update in tuberculosis and nontuberculous mycobacterial infections 2013.

PMID- 24735032
TI  - Official American Thoracic Society technical standards: spirometry in the
      occupational setting.
AB  - PURPOSE: This document addresses aspects of the performance and interpretation of
      spirometry that are particularly important in the workplace, where inhalation
      exposures can affect lung function and cause or exacerbate lung diseases, such as
      asthma, chronic obstructive pulmonary disease, or fibrosis. METHODS: Issues that
      previous American Thoracic Society spirometry statements did not adequately
      address with respect to the workplace were identified for systematic review.
      Medline 1950-2012 and Embase 1980-2012 were searched for evidence related to the
      following: training for spirometry technicians; testing posture; appropriate
      reference values to use for Asians in North America; and interpretative
      strategies for analyzing longitudinal change in lung function. The evidence was
      reviewed and technical recommendations were developed. RESULTS: Spirometry
      performed in the work setting should be part of a comprehensive workplace
      respiratory health program. Effective technician training and feedback can
      improve the quality of spirometry testing. Posture-related changes in FEV1 and
      FVC, although small, may impact interpretation, so testing posture should be kept
      consistent and documented on repeat testing. Until North American Asian-specific
      equations are developed, applying a correction factor of 0.88 to white reference
      values is considered reasonable when testing Asian American individuals in North
      America. Current spirometry should be compared with previous tests. Excessive
      loss in FEV1 over time should be evaluated using either a percentage decline (15%
      plus loss expected due to aging) or one of the other approaches discussed, taking
      into consideration testing variability, worker exposures, symptoms, and other
      clinical information. CONCLUSIONS: Important aspects of workplace spirometry are
      discussed and recommendations are provided for the performance and interpretation
      of workplace spirometry.

PMID- 24735033
TI  - Lung cancer screening, targeted temperature after cardiac arrest, and vasopressin
      and steroids in cardiac arrest.

PMID- 24735034
TI  - Beyond removal of endobronchial foreign body.

PMID- 24735035
TI  - Heterogeneity in the definition of mechanical ventilation duration and ventilator
      free days.

PMID- 24735036
TI  - A novel predictor of cancer malignancy: up-regulation of myristoylated alanine
      rich C kinase substrate phosphorylation in lung cancer.

PMID- 24735037
TI  - Intelectin-1 is a prominent protein constituent of pathologic mucus associated
      with eosinophilic airway inflammation in asthma.

PMID- 24735038
TI  - Antioxidants in the intensive care unit.

PMID- 24735039
TI  - Classification of the idiopathic interstitial pneumonias.

PMID- 24735040
TI  - Reply: antioxidants in the intensive care unit.

PMID- 24735041
TI  - Ventilatory long-term facilitation in humans.

PMID- 24735042
TI  - A unique presentation of a rare congenital anomaly. Double scimitar veins.

PMID- 24735043
TI  - Treatment of bronchopulmonary dyplasia (BPD).

PMID- 24735044
TI  - Abstracts of the 44th Annual Scientific Meeting of the Australian and New Zealand
      Society of Nuclear Medicine (ANZSNM), 25-28 April 2014, Adelaide, Australia.

PMID- 24735045
TI  - Comparison of the h-Index Scores Among Pathogens Identified as Emerging Hazards
      in North America.
AB  - Disease surveillance must assess the relative importance of pathogen hazards.
      Here, we use the Hirsch index (h-index) as a novel method to identify and rank
      infectious pathogens that are likely to be a hazard to human health in the North
      American region. This bibliometric index was developed to quantify an
      individual's scientific research output and was recently used as a proxy measure
      for pathogen impact. Analysis of more than 3000 infectious organisms indicated
      that 651 were human pathogen species that had been recorded in the North American
      region. The h-index of these pathogens ranged from 0 to 584. The h-index of
      emerging pathogens was greater than non-emerging pathogens as was the h-index of
      frequently pathogenic pathogens when compared to non-pathogenic pathogens. As
      expected, the h-index of pathogens varied over time between 1960 and 2011. We
      discuss how the h-index can contribute to pathogen prioritization and as an
      indicator of pathogen emergence. 

PMID- 24735046
TI  - Organocatalyzed enantioselective Mannich reaction of pyrazoleamides with isatin
      derived ketimines.
AB  - The first organocatalytic enantioselective Mannich reaction of pyrazoleamides
      with isatin-derived N-Boc ketimines has been developed to afford 2-oxindole-based
      chiral beta-amino amides in good yields (84-97%) with excellent diastereo- and
      enantioselectivities (up to 99:1 dr and >99% ee). 

PMID- 24735047
TI  - Development of the spittlebug Mahanarva fimbriolata under varying photophase
      conditions.
AB  - The effects of varying photophase conditions on biological parameters of
      Mahanarva fimbriolata (Stal) (Hemiptera: Cercopidae), nymphs and adults were
      evaluated. Eggs of a late developmental stage were placed near sugarcane roots
      (cultivar RB739735) maintained in a greenhouse (21 +/- 7  degrees C, 90 +/- 10%
      RH). Nymphs and adults were exposed to the following photophase conditions: (a)
      13:11 L:D as nymphs and adults, (b) 13:11 as nymphs and 12:12 as adults, (c)
      12:12 as nymphs and adults, and d) 12:12 as nymphs and 13:11 as adults. Exposure
      of nymphs to 13 hr of light significantly reduced the duration of the nymphal
      stage and the number of nymphs that matured to adults. The duration of the
      nymphal stage was longer in individuals developing into females than in those
      developing into males. There was an increase in the longevity of adults kept at
      13 hr of light since the nymphal stage. The average longevity of adult males and
      females was approximately the same. The sex ratio was similar under all
      photophase conditions. The life cycle of insects kept at 12 and 13 hr of light
      during nymphal and adult stages respectively was extended. The total life cycle
      was significantly longer in M. fimbriolata females than males. The different
      photophase conditions did not affect the reproductive potential of M.
      fimbriolata. Females produced more diapausing than non-diapausing eggs, except
      when under 13- and 12-hr light conditions. There was no significant difference in
      the number of diapausing and non-diapausing eggs produced by females under the
      other photophase conditions.

PMID- 24735048
TI  - Nutrient-related changes in the toxicity of field blooms of the cyanobacterium,
      Cylindrospermopsis raciborskii.
AB  - Nutrients have the capacity to change cyanobacterial toxin loads via growth
      related toxin production, or shifts in the dominance of toxic and nontoxic
      strains. This study examined the effect of nitrogen (N) and phosphorus on cell
      division and strain-related changes in production of the toxins,
      cylindrospermopsins (CYNs) by the cyanobacterium, Cylindrospermopsis raciborskii.
      Two short-term experiments were conducted with mixed phytoplankton populations
      dominated by C. raciborskii in a subtropical reservoir where treatments had
      nitrate (NO3 ), urea (U) and inorganic phosphorus (P) added alone or in
      combination. Cell division rates of C. raciborskii were only statistically higher
      than the control on day 5 when U and P were co-supplied. In contrast, cell quotas
      of CYNs (QCYNS ) increased significantly in treatments where P was supplied,
      irrespective of whether N was supplied, and this increase was not necessarily
      related to cell division rates. Increased QCYNS did correlate with an increase in
      the proportion of the cyrA toxin gene to 16S genes in the C. raciborskii
      dominated cyanobacterial population. Therefore, changes in strain dominance are
      the most likely factor driving differences in toxin production between
      treatments. Our study has demonstrated differential effects of nutrients on cell
      division and strain dominance reflecting a C. raciborskii population with a range
      of strategies in response to environmental conditions.

PMID- 24735049
TI  - Molecular recognition and organizational and polyvalent effects in vesicles
      induce the formation of artificial multicompartment cells as model systems of
      eukaryotes.
AB  - Researchers have become increasingly interested in the preparation and
      characterization of artificial cells based on amphiphilic molecules. In
      particular, artificial cells with multiple compartments are primitive mimics of
      the structure of eukaryotic cells. Endosymbiotic theory, widely accepted among
      biologists, states that eukaryotic cells arose from the assembly of prokaryotic
      cells inside other cells. Therefore, replicating this process in a synthetic
      system could allow researchers to model molecular and supramolecular processes
      that occur in living cells, shed light on mass and energy transport through cell
      membranes, and provide a unique, isolated space for conducting chemical
      reactions. In addition, such structures can serve as drug delivery systems that
      encapsulate both bioactive and nonbiocompatible compounds. In this Account, we
      present various coating, incubation, and electrofusion strategies for forming
      multicompartment vesicle systems, and we are focusing on strategies that rely on
      involving molecular recognition of complementary vesicles. All these methods
      afforded multicompartment systems with similar structures, and these
      nanoparticles have potential applications as drug delivery systems or
      nanoreactors for conducting diverse reactions. The complementarity of interacting
      vesicles allows these artificial cells to form, and the organization and
      polyvalency of these interacting vesicles further promote their formation. The
      incorporation of cholesterol in the bilayer membrane and the introduction of PEG
      chains at the surface of the interacting vesicles also support the structure of
      these multicompartment systems. PEG chains appear to destabilize the bilayers,
      which facilitates the fusion and transport of the small vesicles to the larger
      ones. Potential applications of these well-structured and reproducibly produced
      multicompartment systems include drug delivery, where researchers could load a
      cocktail of drugs within the encapsulated vesicles, a process that could enhance
      the bioavailability of these substances. In addition, the production of
      artificial cells with multiple compartments provides a platform where researchers
      could carry out individual reactions in small, isolated spaces. Such a reactive
      space can avoid problems that occur when the environment can be destructive to
      reactants or products or when a diverse set of compounds difficult to obtain in a
      conventional reactor space are produced. Our work on these artificial cells with
      multicompartment structures also led us to formulate a hypothesis on the
      processes that possibly generated eukaryotic cells. We hope both that our
      research efforts will excite interest in these nanoparticles and that this
      research could lead to systems designed for specific scientific and technological
      applications and further insights into the evolution of eukaryotic cells.

PMID- 24735050
TI  - The sub/supra-optimal temperature-induced inhibition of photosynthesis and
      oxidative damage in cucumber leaves are alleviated by grafting onto figleaf
      gourd/luffa rootstocks.
AB  - Shoot-root communication is involved in plant stress responses, but its mechanism
      is largely unknown. To determine the role of roots in stress tolerance, cucumber
      (Cucumis sativus) shoots from plants with roots of their own or with figleaf
      gourd (Cucurbita ficifolia, a chilling-tolerant species) or luffa (Luffa
      cylindrica (L.) M. Roem., a heat-tolerant species) rootstocks were exposed to low
      (18/13 degrees C), optimal (27/22 degrees C) and high (36/31 degrees C)
      temperatures, respectively. Grafting onto figleaf gourd and luffa rootstocks
      significantly alleviated chilling and heat-induced reductions, respectively, in
      biomass production and CO(2) assimilation capacity in the shoots, while levels of
      lipid peroxidation and protein oxidation were decreased. Figleaf gourd and luffa
      rootstocks upregulated a subset of stress-responsive genes involved in signal
      transduction (MAPK1 and RBOH), transcriptional regulation (MYB and MYC), protein
      protection (HSP45.9 and HSP70), the antioxidant response (Cu/Zn-SOD, cAPX and
      GR), and photosynthesis (RBCL, RBCS, RCA and FBPase) at low and high growth
      temperatures, respectively, and this was accompanied by increased activity of the
      encoded enzymes and reduced glutathione redox homeostasis in the leaves.
      Moreover, Heat Shock Protein 70 (HSP70) expression in cucumber leaves was
      strongly induced by the luffa rootstock at the high growth temperature but
      slightly induced by the figleaf gourd rootstock at low or high growth
      temperatures. These results indicate that rootstocks could induce significant
      changes in the transcripts of stress-responsive and defense-related genes, and
      the ROS scavenging activity via unknown signals, especially at stressful growth
      temperatures, and this is one of mechanisms involved in the grafting-induced
      stress tolerance.

PMID- 24735051
TI  - The most intriguing question in synesthesia research.
AB  - This discussion paper forms an insightful addition to the synesthesia literature.
      Accompanying a steep increase in recent publications on synesthesia, it helps
      remedy the conspicuous paucity of mechanistic process models explaining the
      condition. The paper furthermore addresses what is arguably among the most
      interesting questions: Why do most synesthetes *not* get confused by their
      additional sensations? This is particularly interesting when phrased in a broader
      context: What are the mechanisms for deciding which of the sensations we
      experience reflect something "real" (phenomena in the outside world) and which
      reflect something that is "not real" (internally generated and private
      phenomena).

PMID- 24735052
TI  - Noise propagation in synthetic gene circuits for metabolic control.
AB  - Dynamic control of enzyme expression can be an effective strategy to engineer
      robust metabolic pathways. It allows a synthetic pathway to self-regulate in
      response to changes in bioreactor conditions or the metabolic state of the host.
      The implementation of this regulatory strategy requires gene circuits that couple
      metabolic signals with the genetic machinery, which is known to be noisy and one
      of the main sources of cell-to-cell variability. One of the unexplored design
      aspects of these circuits is the propagation of biochemical noise between enzyme
      expression and pathway activity. In this article, we quantify the impact of a
      synthetic feedback circuit on the noise in a metabolic product in order to
      propose design criteria to reduce cell-to-cell variability. We consider a
      stochastic model of a catalytic reaction under negative feedback from the product
      to enzyme expression. On the basis of stochastic simulations and analysis, we
      show that, depending on the repression strength and promoter strength,
      transcriptional repression of enzyme expression can amplify or attenuate the
      noise in the number of product molecules. We obtain analytic estimates for the
      metabolic noise as a function of the model parameters and show that noise
      amplification/attenuation is a structural property of the model. We derive an
      analytic condition on the parameters that lead to attenuation of metabolic noise,
      suggesting that a higher promoter sensitivity enlarges the parameter design
      space. In the theoretical case of a switch-like promoter, our analysis reveals
      that the ability of the circuit to attenuate noise is subject to a trade-off
      between the repression strength and promoter strength. 

PMID- 24735053
TI  - Asymmetric hydroformylation catalyzed by RhH(CO)2[(R,S)-Yanphos]: mechanism and
      origin of enantioselectivity.
AB  - Asymmetric hydroformylation (AHF) catalyzed by transition metal (TM) complexes
      bearing chiral phosphorus ligands is one of the most powerful synthetic ways that
      could provide chiral aldehydes directly from alkenes and syngas in one step.
      Experiments have proved the efficiency of Rh catalyst with hybrid phosphorus
      ligands owning two different phosphorus moieties in AHF. Herein the origin of
      enantioselectivity of AHF catalyzed by RhH(CO)2[(R,S)-Yanphos] was studied at
      M06/BSI level using the density functional theory (DFT) method to unveil a
      fundamental understanding on factors contributing to the efficiency in AHF. The
      alkene insertion step is supposed to be the chirality-determining step in the
      whole catalytic cycle of the Rh-Yanphos system. Four possible pathways of styrene
      (Sub1) insertion step (pathways R1, S1, R2, and S2) were discussed; the
      calculated results indicate that pathways R1 and S2 are proposed to be two
      dominant alkene insertion pathways and that styrene tends to adopt apical
      coordination mode (A mode) to Rh center in pathways R1 and S2 compared to
      equatorial coordination mode (E mode) in pathways R2 and S1. The
      enantioselectivity of AHFs of ten alkene substrates (CH2?CH-R, R?Ph, C(?O)OCH3,
      Ph-(p)-Me, Ph-(p)-OMe, Ph-(p)-(i)Bu, Ph-(p)-F, Ph-(p)-Cl, Ph-(o)-F, OC(?O)-Ph and
      O-Ph, corresponding alkenes are abbreviated as Sub1 to Sub10, respectively) were
      also investigated. The predicted chiralities agree well with experimental
      results. The present work suggests that the relative stabilities of coordination
      modes (A/E mode) of alkene to 2 (RhH(CO)[(R,S)-Yanphos]) might be of importance
      in the enantioselectivity of AHF catalyzed by Rh-Yanphos. 

PMID- 24735054
TI  - Immunomodulation in post-metamorphic northern leopard frogs, Lithobates pipiens,
      following larval exposure to polybrominated diphenyl ether.
AB  - Pollutants and disease are factors implicated in amphibian population declines,
      and it is hypothesized that these factors exert a synergistic adverse effect,
      which is mediated by pollutant-induced immunosuppression. Polybrominated diphenyl
      ethers (PBDEs) are ubiquitous pollutants that can exert immunotoxicity, making
      them of interest to test effects on amphibian immune function. We orally exposed
      Lithobates (Rana) pipiens tadpoles to environmentally realistic levels (0-634
      ng/g wet diet) of a pentabromodiphenyl ether mixture (DE-71) from as soon as they
      became free-swimming through metamorphic climax. To assess adaptive immune
      response in juvenile frogs, we used an enzyme-linked immunosorbent assay to
      measure specific IgY production following immunization with keyhole limpet
      hemocyanin (KLH). Specific KLH antibody response was significantly decreased in
      juvenile frogs that had been exposed to PBDEs as tadpoles. When assessing innate
      immune responses, we found significantly different neutrophil counts among
      treatments; however, phagocytic activity of neutrophils was not significantly
      different. Secretion of antimicrobial skin peptides (AMPs) nonsignificantly
      decreased with increasing PBDE concentrations, and no significant effect of PBDE
      treatment was observed on efficacy of AMPs to inhibit chytrid fungus
      (Batrachochytrium dendrobatidis) growth. Our findings demonstrate that
      environmentally realistic concentrations of PBDEs are able to alter immune
      function in frogs; however, further research is needed to determine how these
      alterations impact disease susceptibility in L. pipiens. 

PMID- 24735055
TI  - Estimating age and ethnic variation in the histological prevalence of prostate
      cancer to inform the impact of screening policies.
AB  - OBJECTIVES: To estimate histological prevalence of prostate cancer by age and
      ethnic group. METHODS: A literature review identified autopsy studies of men
      without clinical diagnosis of prostate cancer during their lifetime. A total of
      25 studies fulfilled the inclusion criteria, and a Bayesian logistic meta
      regression was carried out to examine the association between histological
      prevalence, age by decade and ethnic group (white, African American and
      Chinese/Japanese). RESULTS: Histological cancer was estimated to increase with
      age from 2% (95% confidence interval 1-3%) between 20-29 years-of-age to 69% (95%
      confidence interval 51-83%) by 90-99 years-of-age in the white ethnic group. The
      African American group was associated with the highest prevalence of cancer,
      albeit non-significantly (odds ratio 1.2, 95% confidence interval 0.9-1.5),
      whereas the Chinese/Japanese group was significantly associated with the lowest
      prevalence relative to the white group (odds ratio 0.6, 95% confidence interval
      0.4-0.9). CONCLUSIONS: The present study provides an updated and improved
      analysis of the histological prevalence of prostate cancer. The results confirm
      ethnicity as a potential predictor of prevalence, but highlight the need for
      further research in the area. The findings are valuable for understanding the
      epidemiology and natural history of prostate cancer across ethnicities, and
      increasing the body of evidence aimed at estimating benefits and risks associated
      with prostate cancer screening programs.

PMID- 24735056
TI  - Measuring the Intensity of Chronic Pain: Are the Visual Analogue Scale and the
      Verbal Rating Scale Interchangeable?
AB  - OBJECTIVES: The 0 to 100 mm visual analogue scale (VAS) and the five-category
      verbal rating scale (VRS) are commonly used for measuring pain intensity. An open
      question remains as to whether these scales can be used interchangeably to allow
      comparisons between intensities of pain in the clinical setting or increased
      statistical power in pain research. METHODS: Seven hundred and ninety-six
      patients were requested to rate the present intensity of their chronic pain on
      the two scales. Spearman's rank correlation coefficients between VAS and VRS were
      calculated. For testing interchangeability, VAS was transformed into a discrete
      ordinal scale by dividing the entire VAS into five categories, either
      equidistantly (biased) or using frequency distributions of VAS (unbiased). We
      used Goodman-Kruskal's gamma and Wilson's e measures of ordinal association
      quantified the relationships between the transformed VAS and VRS scores and
      Svensson method to evaluate agreement between biased and unbiased discrete VAS
      and VRS scales. RESULTS: Average VAS and VRS scores were 76 +/- 18 mm and
      "severe," respectively. Spearman's rank correlation coefficient values between
      continuous VAS and VRS were 0.77 to 0.85. Goodman-Kruskal's gamma ordinal
      associations between discrete VAS and VRS were 0.82 to 0.92 and 0.90 to 0.98 for
      the biased and unbiased VAS, respectively. Wilson's e measures were 0.51 to 0.61
      and 0.54 to 0.65, accordingly. Svensson analysis showed low probability of
      agreement between both biased (0.66 to 0.76) and unbiased (0.75 to 0.82) VAS and
      VRS. DISCUSSION: Regardless of the relatively high Spearman correlations between
      original VAS and VRS, the low ordinal association and low probability of
      agreement between discrete VAS and VRS suggest that they are not interchangeable.
      Therefore, VAS and VRS should not be used interchangeably in the clinical setting
      or for increased statistical power in pain research.

PMID- 24735057
TI  - Syndrome of inappropriate antidiuretic hormone secretion associated with adult T
      cell leukaemia/lymphoma.

PMID- 24735058
TI  - Gender differences in composite control of cardiovascular risk factors among
      patients with type 2 diabetes.
AB  - OBJECTIVE: Disparities in outcomes for cardiovascular disease (CVD) exist between
      men and women with type 2 diabetes mellitus (T2DM). We examined gender
      differences in composite control of cardiovascular risk factors in a sample of
      adults with T2DM. SUBJECTS AND METHODS: This was a cross-sectional study of 680
      people recruited from three primary care settings. Primary outcomes were
      individual and composite control of CVD risk factors. Control of individual risk
      outcomes was defined as glycosylated hemoglobin A1c (HbA1c) level of <7%, blood
      pressure (BP) of <130/80 mm Hg, and low-density lipoprotein (LDL) cholesterol
      level of <100 mg/dL. Composite control was defined as having all three outcomes
      under control simultaneously. Linear and logistic regression models were used to
      assess differences in individual means and individual and composite outcomes
      control between men and women, while adjusting for relevant covariates. RESULTS:
      Men made up 56% of the sample, approximately 67% were non-Hispanic black, and 78%
      made less than $35,000 annually. Unadjusted mean systolic BP (134 mm Hg vs. 130
      mm Hg, P=0.005) and LDL cholesterol (99.7 mg/dL vs. 87.6 mg/dL, P<0.001) levels
      were significantly higher in women than in men. Adjusted linear regression showed
      mean diastolic BP (beta=3.09; 95% confidence interval 0.56, 5.63) was
      significantly higher in women. Overall, 12.4% of the sample had composite
      control, and women had poorer composite control compared with men (5.9% vs.
      17.3%). Adjusted logistic models showed that men were significantly more likely
      to have composite risk factor control (odds ratio 2.90; 95% confidence interval
      1.37, 6.13) compared with women. CONCLUSIONS: In this sample of adults with T2DM,
      women had significantly lower composite control compared with men, when adjusting
      for relevant confounders. It is imperative that women are informed about CVD risk
      factors, educated on how to reduce them, and aggressively treated to avoid
      adverse outcomes. Additional research involving women is needed to explore and
      reduce disparities in CVD risk between men and women with T2DM.

PMID- 24735059
TI  - Pharmacokinetic-pharmacodynamic modelling of intravenous buprenorphine in
      conscious horses.
AB  - OBJECTIVE: Describe the pharmacokinetics of buprenorphine and norbuprenorphine in
      horses and to relate the plasma buprenorphine concentration to the
      pharmacodynamic effects. STUDY DESIGN: Single phase non-blinded study. ANIMALS:
      Six dedicated research horses, aged 3-10 years and weighing 480-515 kg. METHODS:
      Thermal and mechanical nociceptive thresholds, heart and respiratory rates and
      locomotor activity were measured before and 15, 30, 45 & 60 minutes and 2, 4, 6,
      8, 12 & 24 hours post-administration of 10 MUg kg(-1) buprenorphine IV.
      Intestinal motility was measured 1, 6, 12 & 24 hours after buprenorphine
      administration. Venous blood samples were obtained before administration of
      buprenorphine 10 MUg kg(-1) IV and 1, 2, 4, 6, 10, 15, 30, 45 & 60 minutes, and
      2, 4, 6, 8, 12 & 24 hours afterwards. Plasma buprenorphine and norbuprenorphine
      concentrations were measured using a liquid chromatography-tandem mass
      spectroscopy (LC-MS/MS) assay with solid-phase extraction. A non-compartmental
      method was used for analysis of the plasma concentration-time data and plasma
      buprenorphine concentrations were modelled against two dynamic effects (change in
      thermal threshold and mechanical threshold) using a simple Emax model. RESULTS:
      Plasma buprenorphine concentrations were detectable to 480 minutes in all horses
      and to 720 minutes in two out of six horses. Norbuprenorphine was not detected.
      Thermal thresholds increased from 15 minutes post-buprenorphine administration
      until the 8-12 hour time points. The increase in mechanical threshold ranged from
      3.5 to 6.0 Newtons (median: 4.4 N); and was associated with plasma buprenorphine
      concentrations in the range 0.34-2.45 ng mL(-1) . CONCLUSIONS AND CLINICAL
      RELEVANCE: The suitability of the use of buprenorphine for peri-operative
      analgesia in the horse is supported by the present study.

PMID- 24735060
TI  - PGR5 and NDH pathways in photosynthetic cyclic electron transfer respond
      differently to sublethal treatment with photosystem-interfering herbicides.
AB  - Effects of sublethal levels of the photosystem-interfering herbicides atrazine
      (Atr) and methyl viologen (MV) on photosynthetic electron transport were
      investigated in Arabidopsis thaliana mutants with defects in cyclic electron
      transfer (CET) activity. Analysis based on chlorophyll fluorescence parameters
      showed that pgr5 mutant (a defect in the PGR5 pathway) was more sensitive to both
      Atr and MV than wild type (Wt) and pnsB3 mutant (a defect in the NDH pathway).
      Real-time PCR (polymerase chain reaction) analysis of transcripts indicated that
      Wt plants showed marked increases in transcripts in the PRG5 and NDH pathways
      under treatment with either Atr or MV. In contrast, Atr increased the gene
      transcripts in CET, but MV decreased them in pnsB3 mutant plants. Atr did not
      increase the transcripts, while MV down-regulated them in pgr5 mutant. Immunoblot
      analysis partially supported the changes in the transcripts; that is, the protein
      levels of PGRL1 and PGR5 were increased in pnsB3 mutant, while no protein level
      was increased in pgr5 mutant after the herbicide treatment. The present results
      suggest that cyclic electron transport is very sensitive to photosystem
      interference induced by chemicals and that the PGR5 pathway is very critical for
      regulation. Thus, pgr5 mutants may be useful plants for monitoring photosystem
      interfering herbicides. 

PMID- 24735061
TI  - Collection of patient-reported outcomes;--text messages on mobile phones provide
      valid scores and high response rates.
AB  - BACKGROUND: Patients with inflammatory rheumatic diseases have expressed a need
      for more frequent measurement of relevant outcomes, due to the variations in
      their symptoms during the day and from day to day. At present, patient-reported
      outcomes are extensively collected with questionnaires completed with pen and
      paper. However, as a measurement tool in frequent data collection the
      questionnaires are impractical. In contrast, text messages on mobile phones are
      suitable for frequent data collection. The aim of this study was two-fold; to
      compare daily registrations of patient-reported outcomes assessed with text
      messages on mobile phones (SMS) or with questionnaires completed with pen and
      paper (P&P), with regard to scores and variation of scores, and to examine
      feasibility of the SMS method in a multicentre clinical study. METHODS: To
      compare scores, 21 patients with an inflammatory, rheumatic disease performed
      daily assessments of pain, fatigue, stiffness and ability to carry out daily
      activities on a numeric rating scale (NRS). The patients were asked to assess the
      variables every other day with the SMS method and every other day with the P&P
      method for 28 consecutive days. In total each participant had to answer 14 P&P
      forms and 14 SMS messages. Mean scores and variation, expressed as the pooled
      standard deviation or as the average range between the maximum and minimum scores
      for the two methods, were compared using paired sample t-tests or Wilcoxon Signed
      Rank Test. To examine feasibility, 36 patients with an inflammatory, rheumatic
      disease assessed the same four variables with SMS twice a week for 35 weeks.
      Feasibility of the SMS method was expressed as mean response-rate (%) in the
      total group and per centre. RESULTS: Mean scores, standard deviation of mean
      scores and mean range scores did not differ significantly between the two methods
      (p > 0.05). Response-rate with the SMS method was 97.9% for the whole group and
      for the three centres 97.1%, 98.3% and 98.4%, respectively. CONCLUSION: Outcomes
      assessed on numeric rating scales and reported with text-messages on mobile
      phones or with questionnaires completed with pen and paper provide comparable
      scores. Further, the SMS method provided high response rates (> 97%) in a
      multicentre setting. Our results encourage the use of text messages on mobile
      phones in studies requiring frequent data collection and real-time assessment, as
      in fluctuating diseases such inflammatory, rheumatic diseases.

PMID- 24735062
TI  - Ultrafast molecular dynamics of biofuel extraction for microalgae and bacteria
      milking: blocking membrane folding pathways to damaged lipid-bilayer
      conformations with nanomicelles.
AB  - Cell milking is a 100% renewable green energy for CO2 by extraction of biofuels
      inside the cytosol of photosynthetic micro-organisms as microalgae and bacteria.
      The cells are exposed to a hydrophobic solvent forming holes and cracks through
      their membranes from which the biofuels can leak out. In protein folding, the
      goal would be to find pathways to the unique functional protein conformer.
      However, in the lipid-bilayer interaction with the solvent for milking, the
      objective is to block the pathways for damaged membrane conformations of low free
      energy with undesired nanostructures, using the solvent properties, as shown with
      an ab initio structural bioinformatic model. Statistical thermodynamics is used
      to compute the free energy (including entropy) from the molecular dynamics
      trajectory of the biomolecular system with many conformational changes. This
      model can be extended to the general problem of biomolecules folding as for
      proteins and nucleic acids. Using an adaptation of the Einstein diffusion law,
      the conformational change dynamics of the lipid bilayer depends on the two
      diffusion coefficients of the solvent: D1 before the irreversible folding
      transition time and the much smaller D2 thereafter. In contrast to the n-hexane
      and n-heptane hydrocarbons of smaller size, the residual D2=4.7 * 10(-7)cm(2)/s
      of the n-decane solvent, with the highest partition coefficient among the three
      extractors, is the only to present a D2 value that is significantly below the
      critical threshold of 10(-6)cm(2)/s. Therefore, the membrane would resist to long
      hydrocarbons and the exposed cells would remain viable for milking.

PMID- 24735063
TI  - Ru-catalyzed rearrangement of N-methyl isoxazolidines to N-H 1,3-oxazinanes: a
      strategy of self-hydride transferring cleavage of N-O bonds.
AB  - A strategy of ruthenium-catalyzed self-hydride transferring cleavage of N-O bonds
      was designed and utilized in a cascade 1,3-dipolar cyclization of alkenes and N
      methyl nitrones followed by an N-demethylative rearrangement, furnishing
      synthetically useful N-H 1,3-oxazinanes. 

PMID- 24735064
TI  - Kidney fibrosis is independent of the amount of ascorbic acid in mice with
      unilateral ureteral obstruction.
AB  - In response to sustained damage to a kidney, fibrosis that can be characterized
      as the deposition of a collagenous matrix occurs and consequently causes chronic
      kidney failure. Because most animals used in experiments synthesize ascorbic acid
      (AsA) from glucose, the roles of AsA in fibrotic kidney diseases are largely
      unknown. Unilateral ureteric obstruction (UUO) mimics the complex pathophysiology
      of chronic obstructive nephropathy and is an ideal model for the investigation of
      the roles of AsA in kidney failure. We examined the impact of a deficiency of
      Akr1a, a gene that encodes aldehyde reductase and is responsible for the
      production of AsA, on fibrotic damage caused by UUO in mice. Oxidatively modified
      DNA was elevated in wild-type and Akr1a-deficient kidneys as a result of UUO to a
      similar extent, and was only slightly suppressed by the administration of AsA.
      Even though Akrla-deficient mice could produce only about 10% of the AsA produced
      by wild-type mice, no difference was observed in collagen I synthesis under
      pathological conditions. The data implied either a low demand for AsA or the
      presence of another electron donor for collagen I production in the mouse kidney.
      Next, we attempted to elucidate the potential causes for oxidative damage in
      kidney cells during the fibrotic change. We found decreases in mitochondrial
      proteins, particularly in electron transport complexes, at the initial stage of
      the kidney fibrosis. The data imply that a dysfunction of the mitochondria leads
      to an elevation of ROS, which results in kidney fibrosis by stimulating cellular
      transformation to myofibroblasts.

PMID- 24735065
TI  - Measuring adjustment in Japanese juvenile delinquents with learning disabilities
      using Japanese version of Kaufman Assessment Battery for Children II.
AB  - AIM: The aim of this study was to create a profile of the cognitive and academic
      abilities of juvenile delinquents (JD) in Japan using the newly validated
      Japanese version of the Kaufman Assessment Battery for Children, Second Edition
      (KABC-II-J). METHODS: We administered the KABC-II-J to 22 JD (Mage  = 15.9 years,
      standard deviation [SD] = 1.4), 28 typically developing high school students
      (Mage  = 16.0 years, SD = 0.08), and (as controls) 12 special education students
      (Mage  = 16.9, SD = 0.83) with mild intellectual disabilities. RESULTS: We
      observed significant differences between JD and typically developing students on
      learning index of the Mental Process Index, and the vocabulary, reading, writing,
      and mathematics indices on the Achievement Index. JD had lower scores than did
      typically developing high school students. Fourteen JD had a 1 SD discrepancy
      (43%) in scores on these indices. These cases were suspected of having learning
      disabilities. CONCLUSION: The KABC-II-J is a suitable means of assessing academic
      and cognitive problems in JD; professionals working in the field of juvenile
      delinquency should recognize that offenders might have severe academic delays and
      learning disabilities.

PMID- 24735066
TI  - Accurate predictions of forces in the presence of multivalent ions by Poisson
      Boltzmann theory.
AB  - Forces between positively and negatively charged colloidal particles across
      aqueous salt solutions containing multivalent ions are measured directly with the
      atomic force microscope (AFM). The measurements are interpreted quantitatively
      with Poisson-Boltzmann (PB) theory. Thereby, the surface potentials and
      regulation properties of the particle surfaces are extracted from symmetric
      measurements between the same types of particles. This information is used to
      predict force profiles in the asymmetric situations involving different types of
      particles without any adjustable parameters. These predictions turn out to be
      very accurate, which demonstrates that the mean-field PB theory is reliable down
      to distances of about 5 nm. While various reports in the literature indicate that
      this theory should fail due to neglect of ion correlations, such effects seem
      important only at higher concentrations and smaller distances. 

PMID- 24735067
TI  - The emergent relevance of care staff decision-making and situation awareness to
      mobility care in nursing homes: an ethnographic study.
AB  - AIM: To explore mobility care as provided by care staff in nursing homes.
      BACKGROUND: Care staff regularly assist residents with their mobility. Nurses are
      increasingly reliant on such staff to provide safe and quality mobility care.
      However, the nature of care staff decision-making when providing assistance has
      not been fully addressed in the literature. DESIGN: A focused ethnography.
      METHOD: The study was conducted in four nursing homes in Melbourne, Australia.
      Non-participant observations of residents and staff in 2011. Focus groups with 18
      nurses, care and lifestyle staff were conducted at three facilities in 2012.
      Thematic analysis was employed for focus groups and content analysis for
      observation data. Cognitive Continuum Theory and the notion of 'situation
      awareness' assisted data interpretation. FINDINGS: Decision-making during
      mobility care emerged as a major theme. Using Cognitive Continuum Theory as a
      guide, nursing home staff's decision-making was described as ranging from system
      aided, through resident- and peer-aided, to reflective and intuitive. Staff
      seemed aware of the need for resident-aided decision-making consistent with
      person-centred care. Habitual mobility care based on shared mental models
      occurred. It was noted that levels of situation awareness may vary among staff.
      CONCLUSION: Care staff may benefit from support via collaborative and reflective
      practice to develop decision-making skills, situation awareness and person
      centred mobility care. Further research is required to explore the connection
      between staff's skills in mobility care and their decision-making competence as
      well as how these factors link to quality mobility care.

PMID- 24735068
TI  - Abstracts of the Australian Rheumatology Association in conjunction with
      Rheumatology Health Professionals Association 55th Annual Scientific Meeting, 17
      20 May 2014, Hobart, Tasmania.

PMID- 24735070
TI  - 2,2,2-Trifluoroacetophenone: an organocatalyst for an environmentally friendly
      epoxidation of alkenes.
AB  - A cheap, mild, fast, and environmentally friendly oxidation of olefins to the
      corresponding epoxides is reported using polyfluoroalkyl ketones as efficient
      organocatalysts. Namely, 2,2,2-trifluoroacetophenone was identified as an
      improved organocatalyst for the epoxidation of alkenes. Various olefins, mono-,
      di-, and trisubstituted, are epoxidized chemoselectively in high to quantitative
      yields utilizing 2-5 mol % catalyst loading and H2O2 as the green oxidant. 

PMID- 24735069
TI  - Functional magnetic resonance imaging networks induced by intracranial
      stimulation may help defining the epileptogenic zone.
AB  - Patients with medically intractable epilepsy often undergo invasive evaluation
      and surgery, with a 50% success rate. The low success rate is likely due to poor
      identification of the epileptogenic zone (EZ), the brain area causing seizures.
      This work introduces a new method using functional magnetic resonance imaging
      (fMRI) with simultaneous direct electrical stimulation of the brain that could
      help localize the EZ, performed in five patients with medically intractable
      epilepsy undergoing invasive evaluation with intracranial depth electrodes.
      Stimulation occurred in a location near the hypothesized EZ and a location away.
      Electrical recordings in response to stimulation were recorded and compared to
      fMRI. Multiple stimulation parameters were varied, like current and frequency.
      The brain areas showing fMRI response were compared with the areas resected and
      the success of surgery. Robust fMRI maps of activation networks were easily
      produced, which also showed a significant but weak positive correlation between
      quantitative measures of blood-oxygen-level-dependent (BOLD) activity and
      measures of electrical activity in response to direct electrical stimulation
      (mean correlation coefficient of 0.38 for all acquisitions that produced a strong
      BOLD response). For four patients with outcome data at 6 months, successful
      surgical outcome is consistent with the resection of brain areas containing high
      local fMRI activity. In conclusion, this method demonstrates the feasibility of
      simultaneous direct electrical stimulation and fMRI in humans, which allows the
      study of brain connectivity with high resolution and full spatial coverage. This
      innovative technique could be used to better define the localization and
      extension of the EZ in intractable epilepsies, as well as for other functional
      neurosurgical procedures.

PMID- 24735071
TI  - Looking back, looking forward: A historical reflection on psychotherapy process
      research.
AB  - In 1983, a group of 14 prominent psychotherapy process researchers attended a
      workshop sponsored by the US National Institute of Mental Health. Although the
      previous decade had seen a marked emphasis on psychotherapy outcome research,
      there had also been several major advances in the field of process research. The
      goals of the workshop were to review the current state of the field, address
      methodological and conceptual issues, and provide recommendations to advance
      scholarship in this area. In this paper, we summarize the major themes of the
      workshop and consider the degree to which its recommendations have come to
      fruition via subsequent developments in the field. Although 30 years have passed
      since the workshop was held, its insights remain highly relevant to psychotherapy
      process research today. 

PMID- 24735072
TI  - Clinical Presentation Resembling Mucosal Disease Associated with 'HoBi'-like
      Pestivirus in a Field Outbreak.
AB  - The genus Pestivirus of the family Flaviviridae consists of four recognized
      species: Bovine viral diarrhoea virus 1 (BVDV-1), Bovine viral diarrhoea virus 2
      (BVDV-2), Classical swine fever virus (CSFV) and Border disease virus (BDV).
      Recently, atypical pestiviruses ('HoBi'-like pestiviruses) were identified in
      batches of contaminated foetal calf serum and in naturally infected cattle with
      and without clinical symptoms. Here, we describe the first report of a mucosal
      disease-like clinical presentation (MD) associated with a 'HoBi'-like pestivirus
      occurring in a cattle herd. The outbreak was investigated using
      immunohistochemistry, antibody detection, viral isolation and RT-PCR. The
      sequence and phylogenetic analysis of 5'NCR, N(pro) and E2 regions of the RT-PCR
      positive samples showed that four different 'HoBi'-like strains were circulating
      in the herd. The main clinical signs and lesions were observed in the respiratory
      and digestive systems, but skin lesions and corneal opacity were also observed.
      MD characteristic lesions and a pestivirus with cytopathic biotype were detected
      in one calf. The present study is the first report of a MD like presentation
      associated with natural infection with 'HoBi'-like pestivirus. This report
      describes the clinical signs and provides a pathologic framework of an outbreak
      associated with at least two different 'HoBi'-like strains. Based on these
      observations, it appears that these atypical pestiviruses are most likely
      underdiagnosed in Brazilian cattle. 

PMID- 24735074
TI  - Measuring the strength of the horned passalus beetle, Odontotaenius disjunctus:
      revisiting an old topic with modern technology.
AB  - Over a century ago, a pioneering researcher cleverly devised a means to measure
      how much weight the horned passalus beetle, Odontotaenius disjunctus (Illiger)
      (Coleoptera: Passalidae), could pull using a series of springs, pulleys, and
      careful observation. The technology available in modern times now allows for more
      rigorous data collection on this topic, which could have a number of uses in
      scientific investigations. In this study, an apparatus was constructed using a
      dynamometer and a data logger in an effort to ascertain the pulling strength of
      this species. By allowing beetles to pull for 10 min, each beetle's mean and
      maximum pulling force (in Newtons) were obtained for analyses, and whether these
      measures are related was determined. Then, whether factors such as body length,
      thorax size, horn size, or gender affect either measure of strength was
      investigated. Basic body measurements, including horn size, of males versus
      females were compared. The measurements of 38 beetles (20 females, 18 males)
      showed there was no difference in overall body length between sexes, but females
      had greater girth (thorax width) than males, which could translate into larger
      muscle mass. A total of 21 beetles (10 females, 11 males) were tested for pulling
      strength. The grand mean pulling force was 0.14 N, and the grand mean maximum was
      0.78 N. Despite the fact that beetles tended to pull at 20% of their maximum
      capacity most of the time, and that maximum force was over 5 times larger than
      the mean force, the 2 measures were highly correlated, suggesting they may be
      interchangeable for research purposes. Females had twice the pulling strength
      (both maximum and mean force) as males in this species overall, but when the
      larger thorax size of females was considered, the effect of gender was not
      significant. Beetle length was not a significant predictor of pulling force, but
      horn size was associated with maximum force. The best predictor of both measures
      of strength appeared to be thorax size. There are a multitude of interesting
      scientific questions that could be addressed using data on beetle pulling
      strength, and this project serves as a starting point for such work.

PMID- 24735073
TI  - Interleukin-1beta mediates virus-induced m2 muscarinic receptor dysfunction and
      airway hyperreactivity.
AB  - Respiratory viral infections are associated with the majority of asthma attacks.
      Inhibitory M2 receptors on parasympathetic nerves, which normally limit
      acetylcholine (ACh) release, are dysfunctional after respiratory viral infection.
      Because IL-1beta is up-regulated during respiratory viral infections, we
      investigated whether IL-1beta mediates M2 receptor dysfunction during
      parainfluenza virus infection. Virus-infected guinea pigs were pretreated with
      the IL-1beta antagonist anakinra. In the absence of anakinra, viral infection
      increased bronchoconstriction in response to vagal stimulation but not to
      intravenous ACh, and neuronal M2 muscarinic receptors were dysfunctional.
      Pretreatment with anakinra prevented virus-induced increased bronchoconstriction
      and M2 receptor dysfunction. Anakinra did not change smooth muscle M3 muscarinic
      receptor response to ACh, lung viral loads, or blood and bronchoalveolar lavage
      leukocyte populations. Respiratory virus infection decreased M2 receptor mRNA
      expression in parasympathetic ganglia extracted from infected animals, and this
      was prevented by blocking IL-1beta or TNF-alpha. Treatment of SK-N-SH
      neuroblastoma cells or primary cultures of guinea pig parasympathetic neurons
      with IL-1beta directly decreased M2 receptor mRNA, and this was not synergistic
      with TNF-alpha treatment. Treating guinea pig trachea segment with TNF-alpha or
      IL-1beta in vitro increased tracheal contractions in response to activation of
      airway nerves by electrical field stimulation. Blocking IL-1beta during TNF-alpha
      treatment prevented this hyperresponsiveness. These data show that virus-induced
      hyperreactivity and M2 dysfunction involves IL-1beta and TNF-alpha, likely in
      sequence with TNF-alpha causing production of IL-1beta.

PMID- 24735075
TI  - Dynamin 2 regulates actin-mediated spindle migration in mouse oocytes.
AB  - BACKGROUND INFORMATION: During meiosis, a bipolar spindle forms in the central
      cytoplasm of an oocyte and then moves to the cortex to extrude the first polar
      body. This is dependent on the regulation of actin and actin-related molecules.
      Dynamin 2, a large guanosine triphosphatases (GTPase) known to regulate clathrin
      mediated endocytosis, is involved in actin recruitment and actin-based vesicle
      mobility. In this study, we investigated the role of Dynamin 2 in oocyte meiosis.
      RESULTS: Dynamin 2 was localised at the cortex and around the spindles of
      oocytes. Disrupting Dynamin 2 activity by RNAi or an inhibitor resulted in polar
      body extrusion failure. Using time-lapse microscopy to monitor aberrant oocyte
      cytokinesis, the chromosomes were first separated, but then re-joined. Actin
      expression in oocytes was decreased; and actin cap formation was disrupted, which
      was confirmed by the disappearance of cortical-granule-free domains. In addition,
      live cell imaging showed that spindle migration had failed and that spindles were
      arrested centrally in oocytes. This may have been due to the Dynamin-binding
      protein Profilin and actin-related protein 2/3 (ARP2/3) complexes, which
      exhibited dispersed signals after disrupting Dynamin 2 activity. CONCLUSIONS:
      Thus, our results indicate that Dynamin 2 regulates spindle migration and polar
      body extrusion during mouse oocyte meiosis through an actin-based pathway.

PMID- 24735076
TI  - Founders of pediatric pathology: remembering Dr Marie Valdes-Dapena.

PMID- 24735077
TI  - Opposite variations in fumarate and malate dominate metabolic phenotypes of
      Arabidopsis salicylate mutants with abnormal biomass under chilling.
AB  - In chilling conditions (5 degrees C), salicylic acid (SA)-deficient mutants
      (sid2, eds5 and NahG) of Arabidopsis thaliana produced more biomass than wild
      type (Col-0), whereas the SA overproducer cpr1 was extremely stunted. The
      hypothesis that these phenotypes were reflected in metabolism was explored using
      600 MHz (1) H nuclear magnetic resonance (NMR) analysis of unfractionated polar
      shoot extracts. Biomass-related metabolic phenotypes were identified as
      multivariate data models of these NMR 'fingerprints'. These included principal
      components that correlated with biomass. Also, partial least squares-regression
      models were found to predict the relative size of plants in previously unseen
      experiments in different light intensities, or relative size of one genotype from
      the others. The dominant signal in these models was fumarate, which was high in
      SA-deficient mutants, intermediate in Col-0 and low in cpr1 at 5 degrees C. Among
      signals negatively correlated with biomass, malate was prominent. Abundance of
      transcripts of the FUM2 cytosolic fumarase (At5g50950) showed strong positive
      correlation with fumarate levels and with biomass, whereas no significant
      differences were found for the FUM1 mitochondrial fumarase (At2g47510). It was
      confirmed that the morphological effects of SA under chilling find expression in
      the metabolome, with a role of fumarate highlighted.

PMID- 24735078
TI  - Water-accelerated OH addition to sulfur dioxide SO2: direct ab initio molecular
      dynamics (AIMD) study.
AB  - Ionization dynamics of water microsolvated sulfur dioxide SO2(H2O)n (n = 1-3 and
      6) have been investigated by means of direct ab initio molecular dynamics (AIMD)
      method to elucidate the hydration effects of OH addition reaction to SO2
      following the ionization. The calculations showed that the neutral 1:1 complex
      SO2-H2O has a C(s) symmetry and the sulfur of SO2 interacts with the oxygen of
      H2O with an eclipsed form. In the case of ionization of SO2-H2O 1:1 complex (n =
      1), the cation complex composed of [H2O-SO2](+) with a face-to-face form was
      obtained as the product. The OH addition reactions to SO2 were found in larger
      systems (n = 2, 3, and 6) following the ionization. The reaction was expressed as
      SO2(+)(H2O)n -> SO2(OH)...H(+)(H2O)(n-1) (n = 2, 3, and 6). The proton generated
      as (SO2-H2O)(+) -> (HSO3) + H(+) was stabilized by the second water molecule as
      the reaction: H(+) + H2O -> H3O(+). These processes occurred and were completed
      within the cluster. The OH addition mechanism in SO2(+)(H2O)n cluster was
      discussed on the basis of the present results.

PMID- 24735079
TI  - Trade-offs in engineering sugar utilization pathways for titratable control.
AB  - Titratable systems are common tools in metabolic engineering to tune the levels
      of enzymes and cellular components as part of pathway optimization. For nonmodel
      microorganisms with limited genetic tools, inducible sugar utilization pathways
      offer built-in titratable systems. However, these pathways can exhibit
      undesirable single-cell behaviors that hamper the uniform and tunable control of
      gene expression. Here, we applied mathematical modeling and single-cell
      measurements of L-arabinose utilization in Escherichia coli to systematically
      explore how sugar utilization pathways can be altered to achieve desirable
      inducible properties. We found that different pathway alterations, such as the
      removal of catabolism, constitutive expression of high-affinity or low-affinity
      transporters, or further deletion of the other transporters, came with trade-offs
      specific to each alteration. For instance, sugar catabolism improved the
      uniformity and linearity of the response at the cost of requiring higher sugar
      concentrations to induce the pathway. Within these alterations, we also found
      that a uniform and linear response could be achieved with a single alteration:
      constitutively expressing the high-affinity transporter. Equivalent modifications
      to the D-xylose utilization pathway yielded similar responses, demonstrating the
      applicability of our observations. Overall, our findings indicate that there is
      no ideal set of typical alterations when co-opting natural utilization pathways
      for titratable control and suggest design rules for manipulating these pathways
      to advance basic genetic studies and the metabolic engineering of microorganisms
      for optimized chemical production.

PMID- 24735080
TI  - Emissions from South Asian brick production.
AB  - Thirteen South Asian brick kilns were tested to quantify aerosol and gaseous
      pollutant emissions. Particulate matter (PM2.5), carbon monoxide (CO), and
      optical scattering and absorption measurements in the exhaust of six kiln
      technologies demonstrate differences in overall emission profiles and relative
      climate warming resulting from kiln design and fuel choice. Emission factors
      differed between kiln types, in some cases by an order of magnitude. The kilns
      currently dominating the sector had the highest emission factors of PM2.5 and
      light absorbing carbon, while improved Vertical Shaft and Tunnel kilns were lower
      emitters. An improved version of the most common technology in the region, the
      zig-zag kiln, was among the lowest emitting kilns in PM2.5, CO, and light
      absorbing carbon. Emission factors measured here are lower than those currently
      used in emission inventories as inputs to global climate models; 85% lower
      (PM2.5) and 35% lower for elemental carbon (EC) for the most common kiln in the
      region, yet the ratio of EC to total carbon was higher than previously estimated
      (0.96 compared to 0.47). Total annual estimated emissions from the brick industry
      are 120 Tg CO2, 2.5 Tg CO, 0.19 Tg PM2.5, and 0.12 Tg EC. 

PMID- 24735081
TI  - Early effect of dutasteride added to alpha-1 blocker therapy for patients with
      lower urinary tract symptoms associated with benign prostatic hyperplasia.
AB  - OBJECTIVE: To investigate the hypothesis that 5-alpha-reductase inhibitors exert
      early ameliorative effects on voiding and storage symptoms in men with lower
      urinary tract symptom-associated benign prostatic hyperplasia. METHODS: This was
      a prospective study involving the participation of eight outpatient clinics in
      Chiba Prefecture, Japan. The patients received dutasteride (0.5 mg) once daily
      orally for 24 weeks as an add-on to their ongoing therapy with an alpha-1
      blocker. The study patients recorded their urinary symptoms every day for 14 days
      after starting dutasteride. The International Prostate Symptom Score, prostate
      volume, uroflowmetry results, and residual urine volume were checked at 3 and 6
      months after starting dutasteride. RESULTS: A total of eighty-eight patients
      participated in the present study; 74 were eligible for analysis of the early
      effects of dutasteride. The median age was 69.6 years (range 54-89), the median
      prostate volume was 50.3 mL (range 24.7-103.3) and the median International
      Prostate Symptom Score was 17.6 (range 8-35). The proportion of patients with
      International Prostate Symptom Score improvements (>=3 points, or >=25%) or 3
      points or more decreased International Prostate Symptom Score were defined
      effective, 37 (50.0%) and 47 (63.5%) experienced improvement at 1 month after
      administration, respectively. CONCLUSION: This is the first prospective clinical
      study to show the early beneficial effects of 5-alpha-reductase inhibitors for
      lower urinary tract symptom-associated benign prostatic hyperplasia. Patients
      with severe symptoms were found to be responsive to dutasteride. The influence of
      the placebo effect was not denied. Further study is necessary.

PMID- 24735082
TI  - The Relation Between Patients' NRS Pain Scores and Their Desire for Additional
      Opioids after Surgery.
AB  - BACKGROUND: Postoperative pain is commonly assessed through a numerical rating
      scale (NRS), an 11-point scale where 0 indicates no pain and 10 indicates the
      worst imaginable pain. Guidelines advise the administration of analgesics at NRS
      pain scores above 3 or 4. In clinical practice, not all patients with pain scores
      above the treatment threshold are willing to accept additional analgesic
      treatment, especially when opioids are offered. The objective of this study is to
      measure the relation between patients' NRS pain scores and their desire for
      additional opioids. METHODS: This cross-sectional study examined 1,084 patients
      in an academic hospital the day after surgery between January 2010 and June 2010.
      The day after surgery, patients were asked to score their pain and desire for
      opioids. Sensitivity, specificity, positive predictive value, and negative
      predictive value of the desire for opioids and the different NRS thresholds were
      calculated. RESULTS: Only when patients scored an 8 or higher on the NRS did the
      majority express a need for opioids. Many patients did not desire opioids,
      because they considered their pain tolerable, even at an NRS score above 4.
      CONCLUSIONS: With the current guidelines (ie, using pain scores above 3 or 4 for
      prescribing opioids), many patients could be overtreated. Therefore, scores
      generated by the NRS should be interpreted individually.

PMID- 24735083
TI  - Impact of initiating insulin glargine disposable pen versus vial/syringe on real
      world glycemic outcomes and persistence among patients with type 2 diabetes
      mellitus in a large managed care plan: a claims database analysis.
AB  - BACKGROUND: Diabetes accounts for almost 15% of all direct healthcare
      expenditures. Managed care organizations try to reduce costs and improve patient
      outcomes. Increasing patient persistence with antidiabetes treatment could help
      achieve these goals. SUBJECTS AND METHODS: A retrospective study was conducted
      using the Optum Research Database (Optum, Eden Prairie, MN) to analyze clinical
      and economic outcomes associated with initiation of insulin glargine via a
      disposable pen (GLA-P) or vial and syringe (GLA-V) among adult, insulin-naive
      patients with type 2 diabetes mellitus (T2DM). Propensity-matched patient cohorts
      were assessed for persistence with insulin therapy, glycated hemoglobin (A1C),
      hypoglycemic events (based on diagnosis codes), and healthcare costs (total paid
      amount of adjudicated claims) after follow-up at 1 year. RESULTS: In 1,308
      matched patients, persistence was significantly higher (P=0.011) and longer
      (P=0.001) with GLA-P. Follow-up A1C values were significantly lower (P=0.038),
      and decreases in A1C from baseline significantly larger (P=0.043), in GLA-P than
      in GLA-V. Significantly fewer hypoglycemic events (P=0.042) were experienced, and
      a lower rate of diabetes-related inpatient admissions (P=0.008) was reported in
      GLA-P than GLA-V. Despite higher study drug costs with GLA-P than GLA-V, all
      cause and diabetes-related healthcare costs were similar. CONCLUSIONS: In insulin
      naive patients with T2DM, initiation of insulin glargine using the disposable pen
      rather than the vial and syringe is associated with higher persistence, better
      A1C control, and lower rates of hypoglycemia. The higher study drug costs
      associated with pen use do not increase total all-cause or diabetes-related
      healthcare costs. This may help treatment selection for patients with T2DM in a
      managed care setting.

PMID- 24735084
TI  - Factors associated with mortality risk for malignant colonic obstruction in
      elderly patients.
AB  - BACKGROUND: Acute colonic obstruction is the most common complication of
      colorectal cancer (CRC) in elderly patients. Medical treatment has been
      associated with higher perioperative morbidity and mortality rates. There is a
      need for identification of elderly CRC patients who will do poorly so that
      results can be improved. The purpose of this study is to assess the 30-day
      outcome of elderly patients undergoing malignant colonic obstruction procedures
      and identify the associated factors of mortality. METHODS: A review of 233
      elderly patients who received medical procedures for malignant colonic
      obstruction between April 2000 and April 2012 was conducted. Data regarding
      clinical variables, surgical procedures and outcomes, complications, and
      mortality were studied. Univariate and logistic regression analyses were
      performed on mortality risk factors. RESULTS: Patients had a mean age of 78.2
      years (range 70-95). A total of 126 (54.1%) patients were classified ASA III and
      above. Eighty (34.3%) patients had right-sided colonic obstruction. In the 153
      (65.7%) patients with left-sided colonic obstruction, 40 patients received self
      expandable metallic stent (SEMS) treatment and 193 patients received surgery. A
      total of 62.2% (n = 145) patients had post operation complications. The overall
      30-day mortality was 24.5% (n = 57). ASA grading, peritonitis and Dukes staging
      were independent risk factors for mortality. CONCLUSIONS: Medical procedures in
      elderly patients with malignant colonic obstruction are associated with
      significant complications and mortality. Identifying these high-risk patients and
      treating promptly may improve outcomes. SEMS treatment provides a useful
      alternative to surgical intervention.

PMID- 24735085
TI  - Opioid-related mortality and filled prescriptions for buprenorphine and
      methadone.
AB  - INTRODUCTION AND AIMS: To assess opioid-related mortality and correlation with
      filled prescriptions for buprenorphine and methadone. DESIGN AND METHODS: A
      register study, including data from the Swedish Forensic Pathology and Forensic
      Toxicology databases 2003-2010, the Prescribed Drug Register and the National
      Patient Register. RESULTS: A total of 1301 deaths, assessed as related to
      buprenorphine, methadone or heroin, or a combination of them, were studied. The
      largest number of fatalities was related to intake of heroin (n = 776), followed
      by methadone (n = 342) and buprenorphine (n = 168). The total annual number of
      fatal cases related to the studied drugs more than doubled (116 to 255) during
      the study period. There were increases in mortality related to both buprenorphine
      and methadone: from 1 to 49 cases for buprenorphine, and from 19 to 81 cases for
      methadone. Only one-fifth of the fatal cases had a filled prescription for the
      maintenance drug assessed as the cause of death. DISCUSSION AND CONCLUSION: This
      study showed that most fatalities were not related to filled prescriptions of
      maintenance drugs, and a substantial illicit use of buprenorphine and methadone
      resulting in deaths was revealed. To prevent opioid toxicity deaths it is
      important to make efforts not only to reduce drug diversion from maintenance
      programs, but also to improve the control of drug trafficking and other illegal
      sources.

PMID- 24735086
TI  - Chronotropic effect of propofol or alfaxalone following fentanyl administration
      in healthy dogs.
AB  - OBJECTIVE: To compare the effect of alfaxalone and propofol on heart rate (HR)
      and blood pressure (BP) after fentanyl administration in healthy dogs. STUDY
      DESIGN: Prospective, randomised clinical study. ANIMALS: Fifty healthy client
      owned dogs (ASA I/II) requiring general anaesthesia for elective magnetic
      resonance imaging for neurological conditions. METHODS: All dogs received
      fentanyl 7 MUg kg(-1) IV and were allocated randomly to receive either alfaxalone
      (n = 25) or propofol (n = 25) to effect until endotracheal (ET) intubation was
      possible. Heart rate and oscillometric BP were measured before fentanyl
      (baseline), after fentanyl (Time F) and after ET intubation (Time GA). Post
      induction apnoea were recorded. Data were analysed using Fisher's exact test,
      Mann Whitney U test and one-way anova for repeated measures as appropriate; p
      value <0.05 was considered significant. RESULTS: Dogs receiving propofol showed a
      greater decrease in HR (-14 beat minute(-1) , range -47 to 10) compared to
      alfaxalone (1 beat minute(-1) , range -33 to 26) (p = 0.0116). Blood pressure
      decreased over the three time periods with no difference between groups.
      Incidence of post-induction apnoea was not different between groups. CONCLUSION:
      Following fentanyl administration, anaesthetic induction with propofol resulted
      in a greater negative chronotropic effect while alfaxalone preserved or increased
      HR. CLINICAL RELEVANCE: Following fentanyl administration, HR decreases more
      frequently when propofol rather than alfaxalone is used as induction agent.
      However, given the high individual variability and the small change in predicted
      HR (-7.7 beats per minute after propofol), the clinical impact arising from
      choosing propofol or alfaxalone is likely to be small in healthy animals. Further
      studies in dogs with myocardial disease and altered haemodynamics are warranted.

PMID- 24735087
TI  - Reliability and validity of Brief Problem Monitor, an abbreviated form of the
      Child Behavior Checklist.
AB  - AIM: The parent form of the 113-item Child Behavior Checklist (CBCL) is widely
      utilized by child psychiatrists and psychologists. This report examines the
      reliability and validity of a recently developed abbreviated version of the CBCL,
      the Brief Problem Monitor (BPM). METHODS: Caregivers (n = 567) completed the CBCL
      online and the 19 BPM items were examined separately. RESULTS: Internal
      consistency of the BPM was high (Cronbach's alpha = 0.91) and satisfactory for
      the Internalizing (0.78), Externalizing (0.86), and Attention (0.87) scales. High
      correlations between the CBCL and BPM were identified for the total score (r =
      0.95) as well as the Internalizing (0.86), Externalizing (0.93), and Attention
      (0.97) scales. The BPM and scales were sensitive and identified significantly
      higher behavioral and emotional problems among children whose caregiver reported
      a psychiatric diagnosis of attention-deficit hyperactivity disorder, bipolar
      disorder, depression, anxiety, developmental disabilities, or autism spectrum
      disorders relative to a comparison group that had not been diagnosed with these
      disorders. BPM ratings also differed by the socioeconomic status and education of
      the caregiver. Mothers with higher annual incomes rated their children as having
      38.8% fewer total problems (Cohen's d = 0.62) as well as 42.8% lower
      Internalizing (d = 0.53), 44.1% less Externalizing (d = 0.62), and 30.9%
      decreased Attention (d = 0.39). A similar pattern was evident for maternal
      education (d = 0.30-0.65). CONCLUSION: Overall, these findings provide strong
      psychometric support for the BPM, although the differences based on the
      characteristics of the parent indicate that additional information from other
      sources (e.g., teachers) should be obtained to complement parental reports.

PMID- 24735088
TI  - A comparison of two milling strategies to reduce the mycotoxin deoxynivalenol in
      barley.
AB  - Winter barley (Hordeum vulgare L.), a potential feedstock for fuel ethanol
      production, may be contaminated with the trichothecene mycotoxin deoxynivalenol
      (DON). DON is a threat to feed and food safety in the United States and may
      become concentrated during the production of distillers dried grains with
      solubles (DDGS). DDGS is a coproduct of fuel ethanol production and is
      increasingly being used as feed for domestic animals. Therefore, new strategies
      to reduce the threat of DON in DDGS need to be developed and implemented for
      grain destined for fuel ethanol production. It is known that large concentrations
      of DON accumulate in the hulls of wheat and barley. Consequently, improved
      methods are needed to carefully remove the hull from the grain and preserve the
      starchy endosperm. Whole kernels from five Virginia winter barley genotypes were
      used to evaluate the abilities of two different milling strategies (roller
      milling and precision milling (FitzMill)) for their ability to remove the hull
      enriched tissue from the kernel while maintaining starch levels and reducing DON
      levels in the endosperm-enriched tissue. After whole kernels were milled, DON and
      starch levels were quantified in the hull-enriched fractions and endosperm
      enriched fractions. Initial milling experiments demonstrated that the precision
      mill system (6 min run time) is able to reduce more DON than the roller mill but
      with higher starch losses. The average percent DON removed from the kernel with
      the roller mill was 36.7% +/- 5.5 and the average percent DON removed from the
      dehulled kernel with the precision mill was 85.1% +/- 9.0. Endosperm-enriched
      fractions collected from the roller mill and precision mill contained starch
      levels ranging from 49.0% +/- 12.1 to 59.1% +/- 0.5 and 58.5% +/- 1.6 to 65.3% +/
      3.9, respectively. On average, the precision mill removed a mass of 23.1% +/-
      6.8 and resulted in starch losses of 9.6% +/- 6.3, but produced an endosperm
      enriched fraction with relatively very little average DON (5.5 +/- 2.7 MUg g(
      1)). In contrast, on average, the roller mill removed a mass of 12.2% +/- 1.6 and
      resulted in starch losses of 2.1% +/- 0.5, but produced an endosperm-enriched
      fraction with high average DON (20.7 +/- 13.5 MUg g(-1)). In a time course
      precision milling experiment, we tested barley genotypes Nomini, Atlantic, and
      VA96-44-304 and attempted to reduce the starch loss seen in the first experiment
      while maintaining low DON concentrations. Decreasing the run time of the
      precision mill from 5 to 2 min, reduced starch loss at the expense of higher DON
      concentrations. Aspirated fractions revealed that the precision milled hull
      enriched fraction contained endosperm-enriched components that were highly
      contaminated with DON. This work has important implications for the reduction of
      mycotoxins such as DON in barley fuel ethanol coproducts and barley enriched
      animal feeds and human foods. 

PMID- 24735089
TI  - Surface modification of polydimethylsiloxane with a covalent antithrombin-heparin
      complex to prevent thrombosis.
AB  - To prevent coagulation in contact with blood, polydimethylsiloxane (PDMS) was
      modified with an antithrombin-heparin (ATH) covalent complex using polyethylene
      glycol (PEG) as a linker/spacer. Using NHS chemistry, ATH was attached covalently
      to the distal chain end of the immobilized PEG linker. Surfaces were
      characterized by contact angle and X-ray photoelectron spectroscopy; attachment
      was confirmed by decrease in contact angles and an increase in nitrogen content
      as determined by X-ray photoelectron spectroscopy. Protein interactions in plasma
      were investigated using radiolabeled proteins added to plasma as tracers, and by
      immunoblotting of eluted proteins. Modification of PDMS with PEG alone was
      effective in reducing non-specific protein adsorption; attachment of ATH at the
      distal end of the PEG chains did not significantly affect protein resistance. It
      was shown that surfaces modified with ATH bound antithrombin selectively from
      plasma through the pentasaccharide sequence on the heparin moiety of ATH,
      indicating the ability of the ATH-modified surfaces to inhibit coagulation. Using
      thromboelastography, the effect of ATH modification on plasma coagulation was
      evaluated directly. It was found that initiation of coagulation was delayed and
      the time to clot was prolonged on PDMS modified with ATH/PEG compared to
      controls. For comparison, surfaces modified in a similar way with heparin were
      prepared and investigated using the same methods. The data suggest that the ATH
      modified surfaces have superior anticoagulant properties compared to those
      modified with heparin. 

PMID- 24735090
TI  - Proton transfer in host-guest complexation between a difunctional pillar[5]arene
      and alkyldiamines.
AB  - Host-guest complexation between a novel difunctional pillar[5]arene-based host H
      and alkyldiamines was fully investigated in both solution and the solid state.
      Proton transfer from the carboxylic acid groups to the amine units occurred in
      the principle by undergoing an acid-base reaction. Driven by the cooperativity of
      electrostatic interactions, multiple C-H...pi interactions, and H-bonds, the
      guests penetrated into the cavity of H to form pseudorotaxane-type inclusion
      complexes with relatively high binding affinities. 

PMID- 24735091
TI  - Are competence frameworks fit for practice? Examining the validity of competence
      frameworks for CBT, psychodynamic, and humanistic therapies.
AB  - Practitioners transporting psychological therapies from a research context to
      clinical settings need to know what competences they should demonstrate to
      maintain congruence with the evidence base. This study explores the validity of a
      suite of competence frameworks for cognitive behavior therapy (CBT), humanistic,
      and psychodynamic therapies developed to aid the transportation process.
      Experienced psychological therapists (N = 111) undertook a Q-sort of 100 items,
      drawn from frameworks representing each of the modalities and including a set of
      pantheoretical generic competences, rating items as characteristic or
      uncharacteristic of their orientation. There were significant differences in the
      way competences were assigned, with practitioners strongly favoring items from
      their own modality framework and eschewing items from the others. These results
      confirm the validity of the items within the frameworks; their utility and
      application is discussed. 

PMID- 24735094
TI  - Attachment chemistry of PCBM to a primary-amine-terminated organic monolayer on a
      Si(111) surface.
AB  - Interfacing multifunctional molecules with semiconductor surfaces has a variety
      of applications; however, it is important to understand the selectivity of target
      surface reactions to produce the surface with desired functionality. In this
      work, a silicon surface modified with 1-amino-10-undecene was reacted with [6,6]
      phenyl-C61-butyric acid methyl ester (PCBM) in toluene. Two possible competing
      reactions for PCBM, via the ester group and by direct attachment to the C60
      portion, are analyzed. X-ray photoelectron spectroscopy, atomic force microscopy,
      Fourier-transform infrared spectroscopy, and time-of-flight secondary ion mass
      spectroscopy, supplemented by density functional theory calculations, suggest
      that despite the similarity of the energetics for those two reaction pathways,
      predominant chemisorption occurs via the direct attachment of the C60 cage to the
      primary amino group of the functionalized silicon surface. 

PMID- 24735092
TI  - Spatial-temporal Variations of Bovine Tuberculosis Incidence in France between
      1965 and 2000.
AB  - We analysed the spatiotemporal variations of bovine tuberculosis (bTB) incidence
      between 1965 and 2000 in France at the department level (95 areas). Using a
      Bayesian space-time model, we studied the association between the evolution of
      bTB incidence and changes of cattle population structure and of herd management
      practices. Several spatiotemporal hierarchical Bayesian models were compared, and
      the deviance information criterion was used to select the best of them. Southern
      France remained a high-risk area over the analysed period, whereas central and
      western regions were low-risk areas. Besides the frequency of tuberculin skin
      testing (fixed according to bTB incidence in the preceding years), four factors
      were associated with an increased risk of bTB: the average herd density and size,
      the percentage of dairy cows in the cattle population, and the percentage of
      permanent grassland in cultivated surfaces area. These four factors are linked to
      the progressive professionalization and specialization of cattle farming, with
      the disappearance of family farms and of the intensification of breeding systems
      (especially in dairy farms after the application of the milk quota system in the
      1980s). Both trends probably played a significant role in reducing the risk of
      bTB in France between 1965 and 2000, besides mandatory detection and control
      procedures. 

PMID- 24735093
TI  - Prognostic factors for survival of patients with ampullary carcinoma after local
      resection.
AB  - BACKGROUND: Local resection (LR) is a potentially effective alternative to
      pancreaticoduodenectomy for treatment of ampullary cancer, but the prognostic
      factors remain undefined. The purpose of this study was to identify the
      prognostic factors for ampullary cancer patients who had undergone LR. METHODS:
      We retrospectively reviewed the clinical, pathological data and surgical approach
      of 34 ampullary cancer patients who had undergone LR during 1996-2009 at People's
      Liberation Army General Hospital. Prognostic factors for survival and recurrence
      were analysed. RESULTS: The 1-, 3- and 5-year survival rates of the patients were
      97.1, 69.5 and 53.7%, respectively. The gender, age, preoperative bilirubin
      levels, CA19-9 levels and preoperative biopsy did not correlate with the survival
      rates. The survival rates of patient with T1 and T2 tumours were superior to that
      of patients with T3 tumours (P = 0.000). Tumour size, surgical margin status and
      the extent of differentiation had no effect on survival rates (P = 0.464, P =
      0.601 and P = 0.121, respectively). The survival rate of patients who had
      extraduodenal LR (12 cases) was superior to that of patients who had
      transduodenal LR (22 cases) (P = 0.026). Tumour recurrence occurred in 14 (41.2%)
      patients. Tumour infiltration (P = 0.014) correlated with the recurrence.
      CONCLUSION: The degree of tumour infiltration is the pathological factor that
      most affects the survival of ampullary cancer patients who undergo LR.
      Extraduodenal LR is a promising surgical procedure, the efficacy of which is
      superior to that of transduodenal LR. The depth of tumour invasion correlated
      with the recurrence.

PMID- 24735095
TI  - Nutrient variability in phloem: examining changes in K, Mg, Zn and Fe
      concentration during grain loading in common wheat (Triticum aestivum).
AB  - In wheat, nutrients are transported to seeds via the phloem yet access to this
      vascular tissue for exudate collection and quantitative analysis of elemental
      composition is difficult. The purest phloem is collected through the use of aphid
      stylectomy with volumes of exudate collected normally in the range of 20-500 nl.
      In this work a new method using inductively coupled plasma mass spectroscopy (ICP
      MS) was developed to measure the concentration of K, Mg, Zn and Fe in volumes of
      wheat (Triticum aestivum, genotype Samnyt 16) phloem as small as 15.5 nl. This
      improved method was used to observe changes in phloem nutrient concentration
      during the grain loading period. There were statistically significant increases
      in phloem Mg and Zn concentration and a significant decrease in K over the period
      from 1-2 days after anthesis (DAA) to 9-12 DAA. During this period, there was no
      statistically significant change in phloem Fe concentration. 

PMID- 24735096
TI  - Does Alcohol consumption during multidrug-resistant tuberculosis treatment affect
      outcome?. A population-based study in Kerala, India.
AB  - RATIONALE: India reports the largest number of multidrug-resistant tuberculosis
      cases in the world; yet, no longitudinal study has assessed factors related to
      treatment outcomes under programmatic conditions in the public sector.
      OBJECTIVES: To describe demographic, clinical, and risk characteristics
      associated with treatment outcomes for all patients with multidrug-resistant
      tuberculosis registered in the Revised National Tuberculosis Control Programme,
      Kerala State, India from January 1, 2009 to June 30, 2010. METHODS: Cox
      regression methods were used to calculate adjusted hazard ratios with 95%
      confidence intervals (CIs) to assess factors associated with an unsuccessful
      treatment outcome. MEASUREMENTS AND MAIN RESULTS: Of 179 patients with multidrug
      resistant tuberculosis registered, 112 (63%) had successful treatment outcomes
      (77 bacteriologically cured, 35 treatment completed) and 67 (37%) had
      unsuccessful treatment outcomes (30 died, 26 defaulted, 9 failed treatment, 1
      stopped treatment because of drug-related adverse events, and 1 developed
      extensively drug-resistant tuberculosis). The hazard for unsuccessful outcome was
      significantly higher among patients who consumed alcohol during treatment
      (adjusted hazard ratio, 4.3; 95% CI, 1.1-17.6) than those who did not. Persons
      who consumed alcohol during treatment, on average, missed 18 more intensive-phase
      doses (95% CI, 13-22) than those who did not. Although many patients had diabetes
      (33%), were ever smokers (39%), or had low body mass index (47%), these factors
      were not associated with outcome. CONCLUSION: Overall treatment success was
      greater than global and national averages; however, outcomes among patients
      consuming alcohol remained poor. Integration of care for multidrug-resistant
      tuberculosis and alcoholism should be considered to improve treatment adherence
      and outcomes.

PMID- 24735097
TI  - Thermoresponsive oligomers reduce Escherichia coli O157:H7 biofouling and
      virulence.
AB  - Thermoresponsive polymers have potential biomedical applications for drug
      delivery and tissue engineering. Here, two thermoresponsive oligomers were
      synthesized, viz. oligo(N-isopropylacrylamide) (ONIPAM) and oligo(N
      vinylcaprolactam) (OVCL), and their anti-biofouling abilities investigated
      against enterohemorrhagic E. coli O157:H7, which produces Shiga-like toxins and
      forms biofilms. Biofilm formation (biofouling) is closely related to E. coli
      O157:H7 infection and constitutes a major mechanism of antimicrobial resistance.
      The synthetic OVCL (MW 679) and three commercial OVCLs (up to MW 54,000) at 30
      MUg ml(-1) were found to inhibit biofouling by E. coli O157:H7 at 37  degrees C
      by more than 80% without adversely affecting bacterial growth. The anti
      biofouling activity of ONIPAM was weaker than that of OVCL. However, at 25 
      degrees C, ONIPAM and OVCL did not affect E. coli O157:H7 biofouling.
      Transcriptional analysis showed that OVCL temperature-dependently downregulated
      curli genes in E. coli O157:H7, and this finding was in line with observed
      reductions in fimbriae production and biofouling. In addition, OVCL downregulated
      the Shiga-like toxin genes stx1 and stx2 in E. coli O157:H7 and attenuated its in
      vivo virulence in the nematode Caenorhabditis elegans. These results suggest that
      OVCL has potential use in antivirulence strategies against persistent E. coli
      O157:H7 infection.

PMID- 24735098
TI  - Thinking beyond sickling to better understand pain in sickle cell disease.
AB  - Painful vaso-occlusive crises (VOCs) are the hallmark of sickle cell disease
      (SCD); however, many patients experience frequent daily pain that does not follow
      the pattern of typical VOCs. This pain of variable severity, also referred as
      persistent pain in the SCD literature, contributes to significant morbidity and
      poor quality of life and often fails to respond adequately to standard SCD
      therapies. In this article, we briefly describe types of pain encountered in SCD
      with a special emphasis on persistent pain. We discuss altered pain processing as
      a potential contributing mechanism, which may lead to development and maintenance
      of persistent pain. We describe the advances in the non-SCD pain field that may
      help improve the understanding of SCD pain. We highlight the need for further
      investigation in this area because some of these patients with persistent pain
      may benefit from receiving adjuvant mechanism-based therapies used successfully
      in other non-SCD chronic pain conditions. 

PMID- 24735099
TI  - Modified penile disassembly technique for boys with epispadias and those
      undergoing complete primary repair of exstrophy: long-term outcomes.
AB  - OBJECTIVES: To describe our experience performing the modified penile disassembly
      technique for boys with epispadias and for those undergoing complete primary
      repair of exstrophy. METHODS: Between January 2004 and July 2009, 34 boys
      underwent the modified penile disassembly technique at our institution. The first
      group included 15 boys with bladder exstrophy who underwent complete primary
      repair of exstrophy. The second group comprised 11 boys with penopupic epispadias
      after previous closure of bladder exstrophy. The third group included 8 boys with
      isolated complete epispadias. RESULTS: The age range was 3 months to 8 years
      (median, 9 months). The follow-up time ranged from 36 months to 8 years (mean, 63
      months). A conical-shaped glans with the absence of any ischemic changes occurred
      in 94% of patients. A mild degree of penile dorsal tilt occurred in 11.7% of
      patients, urethrocutanous fistula in 17.6% and meatal stenosis 5.8%. In cases of
      complete primary repair of exstrophy, hydronephrosis occurred in 66.6% of
      patients. Vesicoureteral reflux appeared in 60% of patients; despite suppressive
      antibiotic therapy, 33.3% are awaiting reimplantation. Continence with volitional
      voiding with dry intervals of >=3 h was achieved in 40% of patients. CONCLUSIONS:
      The modified penile disassembly technique can be used in epispadias and complete
      primary repair of exstrophy with excellent cosmetic results. Preservation of the
      distal urethral plate along with both hemiglans avoids shortening and prevents
      occurrence of hypospadias. Complete primary repair of exstrophy is a feasible
      technique with positive effects on continence with preservation of kidney
      function.

PMID- 24735100
TI  - Assessment of a new insulin preparation for implanted pumps used in the treatment
      of type 1 diabetes.
AB  - BACKGROUND: Implanted insulin pumps using the peritoneal route provide long-term
      improvement of glucose control compared with subcutaneous insulin therapy in type
      1 diabetes (T1D) patients. The stability of insulin preparation is critical for a
      safe use in implanted pumps. Insuman implantable((r)) (400 IU/mL) (Sanofi-Aventis
      Deutschland GmbH, Frankfurt am Main, Germany), a recombinant human insulin, has
      been developed as a replacement for Insuplant((r)) (Aventis Pharma, Frankfurt am
      Main, Germany), a semisynthetic insulin, the only one used so far. The aim of the
      study was to demonstrate the noninferiority of Insuman versus Insuplant, in terms
      of safety and effectiveness when used in implanted pumps. SUBJECTS AND METHODS:
      The patients enrolled, currently treated for T1D by the Medtronic MiniMed
      (Northridge, CA) implantable pump model 2007 with Insuplant, were randomized into
      two study arms and received either Insuman or Insuplant for four pump refill
      cycles. Each pump refill cycle was 40+/-5 days. The co-primary end points
      included glycated hemoglobin (HbA1c) change from baseline and pump infusion
      accuracy. RESULTS: In total, 169 patients were randomized. Noninferiority of
      Insuman versus Insuplant was demonstrated both for the HbA1c change from baseline
      (as a percentage) with intergroup difference of 95% confidence interval (
      0.36;+0.11) and for the infusion accuracy assessed by the measured percentage of
      error at pump refill, as shown by intergroup difference of 95% confidence
      interval (-5.81; -0.50), in per-protocol populations, although the insulin daily
      dose was similar. Severe hypoglycemia occurred at least once in 12 versus 11
      patients, respectively, and metabolic or technical adverse events were
      comparable. CONCLUSIONS: Findings suggest that Insuman can safely and effectively
      replace Insuplant in implanted pumps.

PMID- 24735101
TI  - Founders of pediatric pathology: Arthur James McAdams.

PMID- 24735103
TI  - Improvement in day zero recoveries in field soil dissipation studies using larger
      diameter soil samples.
AB  - Obtaining acceptable recovery of the applied test substance at zero time in field
      soil dissipation studies has been a subject of considerable interest among
      scientists conducting regulatory field studies. In particular, achieving
      recoveries of >=90% in soil samples collected immediately after applications in
      most studies has been elusive. This study investigated a modified soil sampling
      method, which could be used not only on day zero but for the entire study
      duration, to see if the recoveries in soil samples, especially in the early
      stages, can be improved. The modified sampling system has demonstrated that
      recoveries averaging 90% are possible and can be routinely obtained on day zero.
      Description of this modified sampling procedure and statistical analysis of the
      data collected for day zero samples are discussed. 

PMID- 24735102
TI  - Lifestyle and host defense mechanisms of the dung beetle, Euoniticellus
      intermedius: the toll signaling pathway.
AB  - The dung beetle, Euoniticellus intermedius (Reiche) (Coleoptera: Scarabaeidae) is
      an important ecological and agricultural agent. Their main activity, the burying
      of dung, improves quality of the soil and reduces pests that could cause illness
      in animals. E. intermedius are therefore important for agriculture and for good
      maintenance of the environment, and are regarded as effective biological control
      agents for parasites of the gastrointestinal tract in livestock. The ability of
      E. intermedius to co-exist comfortably with many microorganisms, some of which
      are important human pathogens, stimulated our interest in its host defense
      strategies. The aim of this study was to investigate the Toll signaling pathway,
      which is strongly activated by fungi. Gene expression associated with fungal
      infection was analyzed by using 2-D gel electrophoresis and mass spectroscopy.
      Furthermore, the partial adult transcriptome was investigated for the presence of
      known immune response genes by using high-throughput sequencing and
      bioinformatics. The results presented here suggest that E. intermedius responds
      to fungal challenge via the Toll signaling pathway.

PMID- 24735104
TI  - Visual variability affects early verb learning.
AB  - Research demonstrates that within-category visual variability facilitates noun
      learning; however, the effect of visual variability on verb learning is unknown.
      We habituated 24-month-old children to a novel verb paired with an animated star
      shaped actor. Across multiple trials, children saw either a single action from an
      action category (identical actions condition, for example, travelling while
      repeatedly changing into a circle shape) or multiple actions from that action
      category (variable actions condition, for example, travelling while changing into
      a circle shape, then a square shape, then a triangle shape). Four test trials
      followed habituation. One paired the habituated verb with a new action from the
      habituated category (e.g., 'dacking' + pentagon shape) and one with a completely
      novel action (e.g., 'dacking' + leg movement). The others paired a new verb with
      a new same-category action (e.g., 'keefing' + pentagon shape), or a completely
      novel category action (e.g., 'keefing' + leg movement). Although all children
      discriminated novel verb/action pairs, children in the identical actions
      condition discriminated trials that included the completely novel verb, while
      children in the variable actions condition discriminated the out-of-category
      action. These data suggest that - as in noun learning - visual variability
      affects verb learning and children's ability to form action categories. 

PMID- 24735105
TI  - Pre-test genetic counseling services for hereditary breast and ovarian cancer
      delivered by non-genetics professionals in the state of Florida.
AB  - Genetic counseling and testing for hereditary breast and ovarian cancer now
      includes practitioners from multiple healthcare professions, specialties, and
      settings. This study examined whether non-genetics professionals (NGPs) perform
      guideline-based patient intake and informed consent before genetic testing. NGPs
      offering BRCA testing services in Florida (n = 386) were surveyed about clinical
      practices. Among 81 respondents (response rate = 22%), approximately half
      reported: sometimes scheduling a separate session for pre-test counseling lasting
      11-30 min prior to testing, discussing familial implications of testing, benefits
      and limitations of risk management options, and discussing the potential
      psychological impact and insurance-related issues. Few constructed a three
      generation pedigree, discussed alternative hereditary cancer syndromes, or the
      meaning of a variant result. This lack of adherence to guideline-based practice
      may result in direct harm to patients and their family members. NGPs who are
      unable to deliver guideline adherent cancer genetics services should focus on
      identification and referral of at-risk patients to in person or telephone
      services provided by genetics professionals. 

PMID- 24735106
TI  - Enhanced olivine carbonation within a basalt as compared to single-phase
      experiments: reevaluating the potential of CO2 mineral sequestration.
AB  - Batch experiments were conducted in water at 150  degrees C and PCO2 = 280 bar on
      a Mg-rich tholeiitic basalt (9.3 wt % MgO and 12.2 wt % CaO) composed of olivine,
      Ti-magnetite, plagioclase, and clinopyroxene. After 45 days of reaction, 56 wt %
      of the initial MgO had reacted with CO2 to form Fe-bearing magnesite,
      (Mg0.8Fe0.2)CO3, along with minor calcium carbonates. The substantial decrease in
      olivine content upon carbonation supports the idea that ferroan magnesite
      formation mainly follows from olivine dissolution. In contrast, in experiments
      performed under similar run durations and P/T conditions with a San Carlos
      olivine separate (47.8 wt % MgO) of similar grain size, only 5 wt % of the
      initial MgO content reacted to form Fe-bearing magnesite. The overall carbonation
      kinetics of the basalt was enhanced by a factor of ca. 40. This could be
      explained by differences in the chemical and textural properties of the secondary
      silica layer that covers reacted olivine grains in both types of sample.
      Consequently, laboratory data obtained on olivine separates might yield a
      conservative estimate of the true carbonation potential of olivine-bearing
      basaltic rocks. 

PMID- 24735107
TI  - Gonadotrophic hormone and reinforcement sensitivity systems in women with
      premenstrual dysphoric disorder.
AB  - AIM: Behavior inhibition and behavior approach system (BIS/BAS) determine the
      sensitivity to aversion and rewarding stimuli, respectively. This study aimed at
      evaluating the BIS/BAS of premenstrual dysphoric disorder (PMDD) and effect of
      estrogen and progesterone on the BIS/BAS. METHODS: Women with PMDD without
      treatment and control subjects were recruited from the community. The PMDD
      diagnosis was based on psychiatric interviewing and the result of two-menstrual
      cycle follow up. A total of 67 women with PMDD and 75 control subjects were
      recruited and entered the final analysis. They were evaluated with BIS/BAS scale
      and for estrogen and progesterone levels in both premenstrual and follicular
      phases. RESULTS: The results revealed that BAS score was higher among women with
      PMDD in both premenstrual and follicular phases. Progesterone level negatively
      correlated with fun-seeking, and its change in the menstrual cycle also
      negatively correlated to a change in fun-seeking score among women with PMDD.
      Women with PMDD had a higher score in BIS in the premenstrual phase and the BIS
      score correlated to depression, anxiety, and hostility among them. CONCLUSION:
      These results suggest reward sensitivity of women with PMDD is vulnerable to the
      effect of progesterone change in the menstrual cycle. Furthermore, the
      sensitivity to aversive stimuli plays an important role involving core symptoms
      of PMDD. The reinforcement sensitivity of PMDD deserves further detailed study.

PMID- 24735108
TI  - Synthesis of 1,5-dideoxy-1,5-iminoribitol C-glycosides through a nitrone-olefin
      cycloaddition domino strategy: identification of pharmacological chaperones of
      mutant human lysosomal beta-galactosidase.
AB  - We report herein a newly developed domino reaction that facilitates the synthesis
      of new 1,5-dideoxy-1,5-iminoribitol iminosugar C-glycosides 7a-e and 8. The key
      intermediate in this approach is a six-membered cyclic sugar nitrone that is
      generated in situ and trapped by an alkene dipolarophile via a [2 + 3]
      cycloaddition reaction to give the corresponding isooxazolidines 10a-e in a "one
      pot" protocol. The iminoribitol C-glycosides 7a-e and 8 were found to be modest
      beta-galactosidase (bGal) inhibitors. However, compounds 7c and 7e showed
      "pharmacological chaperone" activity for mutant lysosomal bGal activity and
      facilitated its recovery in GM1 gangliosidosis patient fibroblasts by 2-6-fold. 

PMID- 24735109
TI  - Formal homologous aldol reactions: interrupting the Nazarov cyclization via
      carboalkoxylation of alkynes.
AB  - Reactions between 1,4-pentadien-3-ones and aryl acetylenes in the presence of
      BF3.OEt2 furnish alpha-phenacyl cyclopentanones via a domino
      electrocyclization/carboalkoxylation reaction sequence. The overall process
      underscores a new mode of interrupted Nazarov trapping, where two new carbon
      carbon bonds are installed with concomitant formation of carbonyl functionality. 

PMID- 24735110
TI  - Feasibility and impact of a post-discharge geriatric evaluation and management
      service for patients from residential care: the Residential Care Intervention
      Program in the Elderly (RECIPE).
AB  - BACKGROUND: Geriatric evaluation and management has become standard care for
      community dwelling older adults following an acute admission to hospital. It is
      unclear whether this approach is beneficial for the frailest older adults living
      in permanent residential care. This study was undertaken to evaluate (1) the
      feasibility and consumer satisfaction with a geriatrician-led supported discharge
      service for older adults living in residential care facilities (RCF) and (2) its
      impact on the uptake of Advanced Care Planning (ACP) and acute health care
      service utilisation. METHODS: In 2002-4 a randomised controlled trial was
      conducted in Melbourne, Australia comparing the geriatrician-led outreach service
      to usual care for RCF residents. Patients were recruited during their acute
      hospital stay and followed up at the RCF for six months. The intervention group
      received a post-discharge home visit within 96 hours, at which a comprehensive
      geriatric assessment was performed and a care plan developed. Participants and
      their families were also offered further meetings to discuss ACPs and document
      Advanced Directives (AD). Additional reviews were made available for assessment
      and management of intercurrent illness within the RCF. Consumer satisfaction was
      surveyed using a postal questionnaire. RESULTS: The study included 116
      participants (57 intervention and 59 controls) with comparable baseline
      characteristics. The service was well received by consumers demonstrated by
      higher satisfaction with care in the intervention group compared to controls (95%
      versus 58%, p = 0.006).AD were completed by 67% of participants/proxy decision
      makers in the intervention group compared to 13% of RCF residents prior to
      service commencement. At six months there was a significant reduction in
      outpatient visits (intervention 21 (37%) versus controls 45 (76%), (p < 0.001),
      but no difference in readmissions rates (39% intervention versus 34% control, p =
      0.6). There was a trend towards reduced hospital bed-day utilisation
      (intervention 271 versus controls 372 days). CONCLUSION: It is feasible to
      provide a supported discharge service that includes geriatrician assessment and
      care planning within a RCF. By expanding the service there is the potential for
      acute health care cost savings by decreasing the demand for outpatient
      consultation and further reducing acute care bed-days.

PMID- 24735111
TI  - Access, excess, and ethics--towards a sustainable distribution model for
      antibiotics.
AB  - The increasing antibiotic resistance is a global threat to health care as we know
      it. Yet there is no model of distribution ready for a new antibiotic that
      balances access against excessive or inappropriate use in rural settings in low-
      and middle-income countries (LMICs) where the burden of communicable diseases is
      high and access to quality health care is low. Departing from a hypothetical
      scenario of rising antibiotic resistance among pneumococci, 11 stakeholders in
      the health systems of various LMICs were interviewed one-on-one to give their
      view on how a new effective antibiotic should be distributed to balance access
      against the risk of inappropriate use. Transcripts were subjected to qualitative
      'framework' analysis. The analysis resulted in four main themes: Barriers to
      rational access to antibiotics; balancing access and excess; learning from other
      communicable diseases; and a system-wide intervention. The tension between access
      to antibiotics and rational use stems from shortcomings found in the health
      systems of LMICs. Constructing a sustainable yet accessible model of antibiotic
      distribution for LMICs is a task of health system-wide proportions, which is why
      we strongly suggest using systems thinking in future research on this issue.

PMID- 24735112
TI  - Understanding and changing human behaviour--antibiotic mainstreaming as an
      approach to facilitate modification of provider and consumer behaviour.
AB  - This paper addresses: 1) Situations where human behaviour is involved in relation
      to antibiotics, focusing on providers and consumers; 2) Theories about human
      behaviour and factors influencing behaviour in relation to antibiotics; 3) How
      behaviour in relation to antibiotics can change; and, 4) Antibiotic mainstreaming
      as an approach to facilitate changes in human behaviour as regards antibiotics.
      Influencing human behaviour in relation to antibiotics is a complex process which
      includes factors like knowledge, attitudes, social norms, socio-economic
      conditions, peer pressure, experiences, and bio-physical and socio-behavioural
      environment. Further, key concepts are often perceived in different ways by
      different individuals. While designing and implementing projects or programmes
      for behavioural change with respect to antibiotics for professionals or consumers
      it is helpful to consider theories or models of behaviour change, e.g. the
      'stages of change model', including pre-contemplation, contemplation,
      preparation, action, and maintenance. People in different stages of change are
      susceptible to different behaviour modification strategies. Application of
      marketing principles to 'global good', so-called 'social marketing', to improve
      'welfare of the individual and society' is gaining increased attention in public
      health. In conclusion, just providing correct knowledge is not sufficient
      although it is a pre-requisite for behaviour modification in the desired
      direction. We can never change the behaviour of any other human, but we can
      facilitate for others to change their own behaviour. One possibility is to
      implement 'antibiotic mainstreaming' as a potentially effective way for behaviour
      modification, i.e. to address consequences for maintaining effective antibiotics
      in all activities and decisions in society.

PMID- 24735113
TI  - Intimate partner, familial and community violence among men who have sex with men
      in Namibia.
AB  - Men who have sex with men in sub-Saharan Africa are known to experience high
      levels of violence, yet little research has focused on their perceptions of
      intimate partner violence (IPV). This study examines the perceived typologies and
      sources of multiple forms of violence, including IPV, family/community violence
      and discrimination from healthcare workers, among men who have sex with men in
      Namibia. Focus-group discussions and in-depth interviews were conducted with a 52
      men residing in five cities across Namibia. Results indicate that violence, in
      varying forms, is commonplace in the lives of men who have sex with men in this
      community, and may be associated with HIV testing patterns. 

PMID- 24735114
TI  - Safety assessment of genetically modified plants with deliberately altered
      composition.
AB  - The development and marketing of 'novel' genetically modified (GM) crops in which
      composition has been deliberately altered poses a challenge to the European Union
      (EU)'s risk assessment processes, which are based on the concept of substantial
      equivalence with a non-GM comparator. This article gives some examples of these
      novel GM crops and summarizes the conclusions of a report that was commissioned
      by the European Food Safety Authority on how the EU's risk assessment processes
      could be adapted to enable their safety to be assessed. 

PMID- 24735115
TI  - Risk assessment of venous thrombosis in families with known hereditary
      thrombophilia: the MARseilles-NImes prediction model.
AB  - BACKGROUND: Although predicting the risk of venous thrombosis (VT) in an
      individual from a family with inherited thrombophilia is of major importance, it
      is often not feasible. OBJECTIVES: To develop a simple risk assessment model that
      improves prediction of the risk of VT for individuals of families with inherited
      thrombophilia. PATIENTS/METHODS: 1201 relatives from 430 families with inherited
      thrombophilia (deficiencies of antithrombin, protein C or protein S, and the
      factor V Leiden and F2 20210A mutations) were recruited at the referral center
      for thrombophilia in Marseilles, France, from 1986 to 2008. One hundred and
      twenty-two individuals had a personal history of VT. Sixteen preselected clinical
      and laboratory variables were used to derive the VT risk score. RESULTS: The
      scores based on the 16 variables and on the five most strongly associated
      variables performed similarly (areas under receiver operating characteristic
      curves of 0.85 and 0.83, respectively). For the five-variable score, named the
      MARNI score, derived from family history score of VT, von Willebrand factor
      antigen levels, age, severity of thrombophilia, and FGG rs2066865, the risk of VT
      ranged from 0.2% for individuals with a score of 0 (n = 186) to > 70% for
      individuals with a score of >= 7 (n = 27). The model was validated with an
      internal bootstrap method. CONCLUSIONS: With the use of a simple scoring system,
      assessment of the risk of VT in subjects from families with inherited
      thrombophilia can be greatly improved. External validation is now needed to
      replicate these findings.

PMID- 24735117
TI  - Anti-factor IXa/X bispecific antibody (ACE910): hemostatic potency against
      ongoing bleeds in a hemophilia A model and the possibility of routine
      supplementation.
AB  - BACKGROUND: We previously reported that a humanized anti-factor IXa/X bispecific
      antibody, hBS23, mimics the function of FVIII even in the presence of FVIII
      inhibitors, and has preventive hemostatic activity against bleeding in an animal
      model of acquired hemophilia A. After further molecular engineering of hBS23, we
      recently identified an improved humanized bispecific antibody, ACE910, for
      clinical investigation. OBJECTIVES: To elucidate the in vivo hemostatic potency
      of ACE910 by examining its effect against ongoing bleeds, and to determine its
      pharmacokinetic parameters for discussion of its potency for prophylactic use.
      METHODS: A non-human primate model of acquired hemophilia A was established by
      injecting anti-primate FVIII neutralizing antibody. When bleeds emerged following
      an artificial bleed-inducing procedure, either ACE910 or recombinant porcine
      FVIII (rpoFVIII) was intravenously administered. rpoFVIII was additionally
      administered twice daily on the following 2 days. Bleeding symptoms were
      monitored for 3 days. A pharmacokinetic study and multiple-dosing simulations of
      ACE910 were also performed. RESULTS: A single bolus of 1 or 3 mg kg-1 ACE910
      showed hemostatic activity comparable to that of 10 U kg-1 (twice daily) rpoFVIII
      against ongoing bleeds. The determined ACE910 pharmacokinetic parameters included
      a long half-life (3 weeks) and high subcutaneous bioavailability (nearly 100%).
      The simulation results based on pharmacokinetic parameters indicated that the
      above hemostatic level could be maintained with once-weekly subcutaneous
      administration of ACE910, suggesting the possibility of more effective
      prophylaxis. CONCLUSIONS: ACE910 may offer an alternative on-demand treatment
      option for patients with hemophilia A, as well as user-friendly and aggressive
      routine supplementation.

PMID- 24735119
TI  - MiR-9 contributes to the developmental differences in CXCR-4 expression in human
      megakaryocytes.

PMID- 24735118
TI  - G protein-coupled receptor kinase 2 moderates recruitment of THP-1 cells to the
      endothelium by limiting histamine-invoked Weibel-Palade body exocytosis.
AB  - BACKGROUND: G protein-coupled receptors (GPCRs) are a major family of signaling
      molecules, central to the regulation of inflammatory responses. Their activation
      upon agonist binding is attenuated by GPCR kinases (GRKs), which desensitize the
      receptors through phosphorylation. G protein-coupled receptor kinase 2(GRK2) down
      regulation in leukocytes has been closely linked to the progression of chronic
      inflammatory disorders such as rheumatoid arthritis and multiple sclerosis.
      Because leukocytes must interact with the endothelium to infiltrate inflamed
      tissues, we hypothesized that GRK2 down-regulation in endothelial cells would
      also be pro-inflammatory. OBJECTIVES: To determine whether GRK2 down-regulation
      in endothelial cells is pro-inflammatory. METHODS: siRNA-mediated ablation of
      GRK2 in human umbilical vein endothelial cells (HUVECs) was used in analyses of
      the role of this kinase. Microscopic and biochemical analyses of Weibel-Palade
      body (WPB) formation and functioning, live cell imaging of calcium concentrations
      and video analyses of adhesion of monocyte-like THP-1 cells provide clear
      evidence of GRK2 function in histamine activation of endothelial cells. RESULTS:
      G protein-coupled receptor kinase 2 depletion in HUVECs increases WPB exocytosis
      and P-selectin-dependent adhesion of THP-1 cells to the endothelial surface upon
      histamine stimulation, relative to controls. Further, live imaging of
      intracellular calcium concentrations reveals amplified histamine receptor
      signaling in GRK2-depleted cells, suggesting GRK2 moderates WPB exocytosis
      through receptor desensitization. CONCLUSIONS: G protein-coupled receptor kinase
      2 deficiency in endothelial cells results in increased pro-inflammatory signaling
      and enhanced leukocyte recruitment to activated endothelial cells. The ability of
      GRK2 to modulate initiation of inflammatory responses in endothelial cells as
      well as leukocytes now places GRK2 at the apex of control of this finely balanced
      process.

PMID- 24735120
TI  - Assessing Potential Risks of Influenza A Virus Transmission at the Pig-Human
      Interface in Thai Small Pig Farms Using a Questionnaire Survey.
AB  - Influenza A viruses pose a major public health threat worldwide, especially due
      to the potential for inter-species transmission. Farmers could be among the first
      people to be infected with a novel reassortant virus in a pig herd and may serve
      as a source of the virus for their communities. In this study, the pig production
      systems of smallholders in rural Thailand were examined to qualitatively evaluate
      the potential risks that may contribute to the spread of influenza A viruses. The
      investigation was based on questionnaire interviews regarding pig farmers'
      practices and trading activities. We found that extensive pig-human contacts,
      commingling of pigs and chickens and suboptimal biosecurity practices adopted by
      farmers and traders may constitute substantial risks for inter-species influenza
      virus transmission, thereby posing a threat to pig populations and human public
      health. The regular practices of using manure as field fertilizer, hiring boars
      from outside and trading activities could contribute to the potential spread of
      influenza viruses in the local community. To mitigate the potential risks of
      influenza A virus transmission and spread in the local community, it is
      recommended that appropriate public health strategies and disease prevention
      policies for farmers and traders should be developed including improving
      biosecurity, encouraging separation of animals raised on farms and minimizing the
      exposure between pigs and humans. Furthermore, surveillance systems for pig
      diseases should be targeted around the festival months, and on-farm
      identification of pigs should be promoted. 

PMID- 24735121
TI  - Fishbone perforation causing duodenocaval fistula and caval thrombus.

PMID- 24735123
TI  - Base stacking in adenosine dimers revealed by femtosecond transient absorption
      spectroscopy.
AB  - Excitons formed in DNA by UV absorption decay via poorly understood pathways that
      can culminate in mutagenic photoproducts. In order to gain insight into how base
      stacking influences UV excited states in DNA, five dinucleosides composed of
      adenosine or 2'-deoxyadenosine units joined by flexible linkers were studied by
      femtosecond transient absorption spectroscopy. In aqueous solution, transient
      absorption signals recorded at pump and probe wavelengths of 267 and 250 nm,
      respectively, show that UV absorption produces excimer states in all dimers that
      decay orders of magnitude more slowly than excitations in a single adenine
      nucleotide. Adding methanol as a cosolvent disrupts pi-pi stacking of the adenine
      moieties and causes the excimer states in all five dinucleosides to vanish for a
      methanol concentration of 80% by volume. These observations confirm that base
      stacking is an essential requirement for the slow decay channel seen in these and
      other DNA model compounds. This channel appears to be insensitive to the precise
      stacking conformation at the instant of photon absorption as long as the bases
      are cofacially stacked. Notably, circular dichroism (CD) spectra of several of
      the dinucleosides are weak and monomer-like and lack the exciton coupling that
      has been emphasized in the past as an indicator of base-stacked structure. For
      these dimers, the coupled transition dipole moments of the two adenines are
      proposed to adopt left- and right-handed arrangements upon stacking with roughly
      equal probability. Although the mechanism behind slow nonradiative decay in DNA
      is still uncertain, these results show that the signature of these states in
      transient absorption experiments can be a more reliable diagnostic of base
      stacking than the occurrence of exciton-coupled CD signals. These observations
      also draw attention to the important role the backbone plays in producing
      structures with axial (helical) chirality. 

PMID- 24735122
TI  - Can comprehensive specialised end-of-life care be provided at home? Lessons from
      a study of an innovative consultant-led community service in the UK.
AB  - The Midhurst Macmillan Specialist Palliative Care Service (MMSPCS) is a UK,
      medical consultant-led, multidisciplinary team aiming to provide round-the-clock
      advice and care, including specialist interventions, in the home, community
      hospitals and care homes. Of 389 referrals in 2010/11, about 85% were for cancer,
      from a population of about 155 000. Using a mixed method approach, the evaluation
      comprised: a retrospective analysis of secondary-care use in the last year of
      life; financial evaluation of the MMSPCS using an Activity Based Costing
      approach; qualitative interviews with patients, carers, health and social care
      staff and MMSPCS staff and volunteers; a postal survey of General Practices; and
      a postal survey of bereaved caregivers using the MMSPCS. The mean cost is about
      3000 GBP (3461 EUR) per patient with mean cost of interventions for cancer
      patients in the last year of life 1900 GBP (2192 EUR). Post-referral, overall
      costs to the system are similar for MMSPCS and hospice-led models; however,
      earlier referral avoided around 20% of total costs in the last year of life.
      Patients and carers reported positive experiences of support, linked to the
      flexible way the service worked. Seventy-one per cent of patients died at home.
      This model may have application elsewhere.

PMID- 24735124
TI  - Capsular hyaluronic acid of equine isolates of Streptococcus zooepidemicus is
      upregulated at temperatures below 35 degrees C.
AB  - REASONS FOR PERFORMING STUDY: Streptococcus zooepidemicus causes opportunist
      respiratory and other infections in the horse. Capsule expression is highly
      variable and known to affect resistance to phagocytosis. Most clinical isolates
      producing small, dry colonies at 37 degrees C produce mucoid colonies at
      temperatures below 35 degrees C. OBJECTIVES: The aim was to understand the
      molecular basis of increased capsule expression by equine isolates of S.
      zooepidemicus at temperatures lower than 35 degrees C. STUDY DESIGN: Cross
      sectional observational study. METHODS: Capsule production by groups of equine S.
      zooepidemicus strains was determined at 23, 30, 35 and 37 degrees C.
      Hyaluronidase (HylC) at 23 and 37 degrees C was measured by quantitative enzyme
      linked immunosorbent assay. Expressions of hasA and hylC at 23 and 37 degrees C
      were measured by quantitative reverse transcriptase-PCR. The covRS genes in
      representative S. zooepidemicus were sequenced and checked for mutations.
      RESULTS: Colonies of randomly selected S. zooepidemicus strains became mucoid or
      showed marked increase in colony mucoidy following the change in temperature to
      23 degrees C. Expression of hasA at 23 degrees C was 45- to 700-fold greater than
      at 37 degrees C. Transcription of hylC at 23 degrees C was 2.5- to 200-fold
      greater than at 37 degrees C, yet enzyme concentrations in cultures were
      significantly higher at 37 degrees C (P<0.05), suggesting that production of HylC
      is regulated post transcriptionally. The covRS gene in S. zooepidemicus was not
      mutated as seen in isolates of Streptococcus pyogenes with increased capsule
      production at 25 degrees C. CONCLUSIONS: Sensitivity of capsule expression to
      temperature above 35 degrees C but not HylC by the general population of equine
      S. zooepidemicus indicates that capsule is not required for extended colonisation
      nor for opportunist invasion. Instead, capsule production at lower than body
      temperature may reflect adaptation to life on skin and mucosal surfaces, where
      hyaluronic acid contributes to adhesion and resistance to desiccation.
      Pathogenicity of S. zooepidemicus following opportunist invasion is possibly
      dependent on factors other than capsule that may be co-regulated with HylC. The
      Summary is available in Chinese - see Supporting information.

PMID- 24735125
TI  - Structure irregularity impedes drop roll-off at superhydrophobic surfaces.
AB  - We study water drop roll-off at superhydrophobic surfaces with different surface
      patterns. Superhydrophobic microcavity surfaces were fabricated in silicon and
      coated with 1H,1H,2H,2H-perfluorodecyltrichlorosilane (FDTS). For the more
      irregular surface patterns, the observed increase in roll-off angles is found to
      be caused by a decrease of the receding contact angle, which in turn is caused by
      an increase of the triple phase contact line of the drops for those more
      irregular surfaces. To understand the observation, we propose to treat the
      microdrops as rigid bodies and apply a torque balance between the torque exerted
      by the projected gravity force and the torque exerted by the adhesion force
      acting along the triple line on the receding side of the drop. This simple model
      provides a proper order of magnitude estimate of the measured effects. 

PMID- 24735126
TI  - Control of invasive marine invertebrates: an experimental evaluation of the use
      of low salinity for managing pest corals (Tubastraea spp.).
AB  - This study investigated the use of low salinity as a killing agent for the
      invasive pest corals Tubastraea coccinea and Tubastraea tagusensis
      (Dendrophylliidae). Experiments investigated the efficacy of different
      salinities, the effect of colony size on susceptibility and the influence of
      length of exposure. Experimental treatments of colonies were carried out in
      aquaria. Colonies were then fixed onto experimental plates and monitored in the
      field periodically over a period of four weeks. The killing effectiveness of low
      salinity depended on the test salinity and the target species, but was
      independent of colony size. Low salinity was fast acting and prejudicial to
      survival: discoloration, necrosis, fragmenting and sloughing, exposure of the
      skeleton and cover by biofoulers occurred post treatment. For T. tagusensis, 50%
      mortality (LC50) after three days occurred at eight practical salinity units
      (PSU); for T. coccinea the LC50 was 2 PSU. Exposure to freshwater for 45-120 min
      resulted in 100% mortality for T. tagusensis, but only the 120 min period was
      100% effective in killing T. coccinea. Freshwater is now routinely used for the
      post-border management of Tubastraea spp. This study also provides insights as to
      how freshwater may be used as a routine biosecurity management tool when applied
      pre-border to shipping vectors potentially transporting non-indigenous marine
      biofouling species.

PMID- 24735127
TI  - Metabolic profiling of the resurrection plant Haberlea rhodopensis during
      desiccation and recovery.
AB  - Desiccation tolerance is among the most important parameters for crop improvement
      under changing environments. Resurrection plants are useful models for both
      theoretical and practical studies. We performed metabolite profiling via gas
      chromatography coupled with mass spectrometry (GC-MS) and high-performance liquid
      chromatography (HPLC) and analyzed the antioxidant capacity of the endemic
      resurrection plant Haberlea rhodopensis at desiccation and recovery. More than
      100 compounds were evaluated. Stress response included changes in both primary
      and secondary metabolic pathways. The high amounts of the specific glycoside
      myconoside and some phenolic acids - e.g. syringic and dihydrocaffeic acid under
      normal conditions tend to show their importance for the priming of H. rhodopensis
      to withstand severe desiccation and oxidative stress. The accumulation of sucrose
      (resulting from starch breakdown), total phenols, beta-aminoisobutyric acid, beta
      sitosterol and alpha-tocopherol increased up to several times at later stages of
      desiccation. Extracts of H. rhodopensis showed high antioxidant capacity at
      stress and normal conditions. Myconoside was with the highest antioxidant
      properties among tested phenolic compounds. Probably, the evolution of
      resurrection plants under various local environments has resulted in unique
      desiccation tolerance with specific metabolic background. In our case, it
      includes the accumulation of a relatively rare compound (myconoside) that
      contributes alone and together with other common metabolites. Further systems
      biology studies on the involvement of carbohydrates, phenolic acids and
      glycosides in the desiccation tolerance and antioxidant capacity of H.
      rhodopensis will definitely help in achieving the final goal - improving crop
      drought tolerance. 

PMID- 24735128
TI  - Immediate antiinflammatory effects of inhaled budesonide in patients with asthma.
AB  - BACKGROUND: In patients with asthma, single doses of inhaled glucocorticosteroids
      (ICS) have been reported to have antiinflammatory actions that can be detected
      several hours after drug administration. However, the onset and duration of the
      effect have not been investigated. We therefore measured airway blood flow
      ([Formula: see text]aw) as an index of airway inflammation to determine the time
      course and dose dependence of the antiinflammatory action of an ICS in 20
      patients with moderate asthma receiving regular ICS treatment. METHODS: [Formula:
      see text]aw and spirometry were measured before and serially for 360 minutes
      after a single inhaled dose of 360 MUg, 720 MUg, and 1,440 MUg budesonide or
      placebo as well as after four repetitive 720-MUg budesonide doses given 30
      minutes apart. RESULTS: Baseline mean [Formula: see text]aw was increased and
      FEV1 was decreased without significant differences among the 5 treatment days.
      After budesonide inhalation, there was a transient, dose-dependent decrease in
      mean [Formula: see text]aw from 12 to 21%, with significant differences from
      baseline at 60 and 90 minutes for the 720-MUg and 1,440-MUg doses (P < 0.05).
      Thirty minutes after four repetitive budesonide administrations, mean [Formula:
      see text]aw was 28% below baseline (P < 0.05) and remained 11% below baseline
      after 270 minutes. There was no change in mean FEV1 after any of the treatments.
      CONCLUSIONS: In subjects with moderate asthma who use ICS regularly, inhaled
      budesonide caused a transient dose-dependent vasoconstriction in the airway,
      thereby reversing one manifestation of airway inflammation. These results suggest
      that a pure controller medication can have immediate beneficial effects not
      paralleled by changes in airflow. Clinical trial registered with
      www.clinicaltrials.gov (NCT 01219738).

PMID- 24735130
TI  - Usefulness of Succinate dehydrogenase B (SDHB) immunohistochemistry in guiding
      mutational screening among patients with pheochromocytoma-paraganglioma
      syndromes.
AB  - Genetic testing of pheochromocytomas (PCC) and paragangliomas (PGL), although
      expensive, is gradually becoming a part of the routine laboratory investigation
      for patients with PCC-PGL syndrome. Recently, Succinate dehydrogenase B (SDHB)
      immunochemistry has been shown to be an excellent indicator of germline mutations
      in the SDH genes and could help significantly reduce cost. This study assesses
      the utility of SDHB immunohistochemical analysis when used to guide genetic
      analysis, with emphasis on cost benefits it could provide in a resource-limited
      setting. Forty-four cases of PCC/PGL characterized by genetic analysis were
      included to determine their SDHB expression pattern by immunohistochemistry. SDHB
      antibody expression was negative among three cases each, with SDHB and SDHD
      mutations. Immunohistochemistry results were positive for all three cases of RET,
      a single case of neurofibromatosis and for two cases with Von Hippel-Lindau (VHL)
      mutations while the remaining two cases with VHL mutations showed a diffuse
      'cytoplasmic blush'. Thirty of the remaining 31 samples demonstrated positive
      staining and were negative for mutations, while a lone sample that was negative
      for staining and mutation was not included in the final analysis as the internal
      control for the sample was not adequately stained. Cost analysis in our settings
      showed that triaging with SDHB immunohistochemistry could potentially reduce
      costs by USD 320-500 per patient. SDHB immunohistochemistry, when used as a guide
      to genetic testing, can significantly reduce the effort, time and costs of
      testing among patients with PCC-PGL, a huge benefit in resource limited settings.

PMID- 24735132
TI  - Systemic sclerosis after silicone injections for facial cosmetic surgery.

PMID- 24735131
TI  - Managing the sugarcane borer, Diatraea saccharalis, and corn earworm, Helicoverpa
      zea, using Bt corn and insecticide treatments.
AB  - The sugarcane borer, Diatraea saccharalis (Fabricius) (Lepidoptera: Crambidae)
      and the corn earworm, Helicoverpa zea (Boddie) (Lepidoptera: Noctuidae), are
      important pests of corn in Brazil and have not been successfully managed, because
      of the difficulty of managing them with pesticides. The objective of this study
      was to evaluate the effect of Bt corn MON810, transformed with a gene from
      Bacillus thuringiensis Berliner (Bacillales: Bacillaceae) insecticide seed
      treatment, and foliar insecticide spray using treatments developed for control of
      the fall armyworm, Spodoptera frugiperda (J. E. Smith) (Lepidoptera: Noctuidae),
      which is the major pest of corn. The experiments were done under field conditions
      in early- and late-planted corn in the state of Rio Grande do Sul, Brazil, and in
      the laboratory. The MON810 corn reduced infestations and damage by D. saccharalis
      and H. zea. The insecticides used in seed treatments or foliar sprays did not
      affect D. saccharalis and H. zea infestations or damage levels. The exception was
      the insecticide seed treatment in non-transformed corn, which reduced early
      infestations of D. saccharalis. The MON810 corn, therefore, can be used for
      managing these two pest species, especially D. saccharalis.

PMID- 24735129
TI  - Intercellular electrical communication in the heart: a new, active role for the
      intercalated disk.
AB  - Cardiac conduction is the propagation of electrical excitation through the heart
      and is responsible for triggering individual myocytes to contract in synchrony.
      Canonically, this process has been thought to occur electrotonically, by means of
      direct flow of ions from cell to cell. The intercalated disk (ID), the site of
      contact between adjacent myocytes, has been viewed as a structure composed of
      mechanical junctions that stabilize the apposition of cell membranes and gap
      junctions which constitute low resistance pathways between cells. However,
      emerging evidence suggests a more active role for structures within the ID in
      mediating intercellular electrical communication by means of non-canonical
      ephaptic mechanisms. This review will discuss the role of the ID in the context
      of the canonical, electrotonic view of conduction and highlight new, emerging
      possibilities of its playing a more active role in ephaptic coupling between
      cardiac myocytes.

PMID- 24735133
TI  - Genetic and bioinformatics analysis of four novel GCK missense variants detected
      in Caucasian families with GCK-MODY phenotype.
AB  - Heterozygous loss-of-function mutations in the glucokinase (GCK) gene cause
      maturity-onset diabetes of the young (MODY) subtype GCK (GCK-MODY/MODY2). GCK
      sequencing revealed 16 distinct mutations (13 missense, 1 nonsense, 1 splice
      site, and 1 frameshift-deletion) co-segregating with hyperglycaemia in 23 GCK
      MODY families. Four missense substitutions (c.718A>G/p.Asn240Asp,
      c.757G>T/p.Val253Phe, c.872A>C/p.Lys291Thr, and c.1151C>T/p.Ala384Val) were novel
      and a founder effect for the nonsense mutation (c.76C>T/p.Gln26*) was supposed.
      We tested whether an accurate bioinformatics approach could strengthen family
      genetic evidence for missense variant pathogenicity in routine diagnostics, where
      wet-lab functional assays are generally unviable. In silico analyses of the novel
      missense variants, including orthologous sequence conservation, amino acid
      substitution (AAS)-pathogenicity predictors, structural modeling and splicing
      predictors, suggested that the AASs and/or the underlying nucleotide changes are
      likely to be pathogenic. This study shows how a careful bioinformatics analysis
      could provide effective suggestions to help molecular-genetic diagnosis in
      absence of wet-lab validations. 

PMID- 24735134
TI  - OpT2mise: a randomized controlled trial to compare insulin pump therapy with
      multiple daily injections in the treatment of type 2 diabetes-research design and
      methods.
AB  - BACKGROUND: In insulin-requiring type 2 diabetes patients, current insulin
      therapy approaches such as basal-alone or basal-bolus multiple daily injections
      (MDI) have not consistently provided achievement of optimal glycemic control.
      Previous studies have suggested a potential benefit of continuous subcutaneous
      insulin infusion (CSII) in these patients. The OpT2mise study is a multicenter,
      randomized, trial comparing CSII with MDI in a large cohort of subjects with
      evidence of persistent hyperglycemia despite previous MDI therapy. SUBJECTS AND
      METHODS: Subjects were enrolled into a run-in period for optimization of their
      MDI insulin regimen. Subjects showing persistent hyperglycemia (glycated
      hemoglobin [HbA1c] >=8% and <=12%) were then randomly assigned to CSII or
      continuing an MDI regimen for a 6-month phase followed by a single crossover of
      the MDI arm, switching to CSII. The primary end point is the between-group
      difference in mean change in HbA1c from baseline to 6 months. Secondary end
      points include change in mean 24-h glucose values, area under the curve and time
      spent in hypoglycemia and hyperglycemia, measures of glycemic excursions, change
      in postprandial hyperglycemia, and evaluation of treatment satisfaction. Safety
      end points include hypoglycemia, hospital admissions, and emergency room visits.
      RESULTS: When subject enrollment was completed in May 2013, 495 subjects had been
      enrolled in the study. The study completion for the primary end point is expected
      in January 2014. CONCLUSIONS: OpT2mise will represent the largest studied
      homogeneous cohort of type 2 diabetes patients with persistent hyperglycemia
      despite optimized MDI therapy. OpT2mise will help define the role of CSII in
      insulin intensification and define its safety, rate of hypoglycemia, patient
      adherence, and patient satisfaction.

PMID- 24735135
TI  - The complete mitochondrial genome of the jumping spider Telamonia vlijmi
      (Araneae: Salticidae).
AB  - The complete mitochondrial genome of a jumping spider Telamonia vlijmi was
      sequenced and its total length is 14,601 bp, with A 35.5%, T 41.8%, C 8.7%, and G
      14.0%. Among protein-coding genes, two genes (CO1 and Cytb) start with TTA,
      uncommon in invertebrate mitogenomes. The standard cloverleaf secondary structure
      was found in 10 tRNA genes and TV-replacement loop was not found in the other 12
      tRNA genes.

PMID- 24735136
TI  - Commentary: scoring models for short-term mortality in alcoholic hepatitis.

PMID- 24735137
TI  - Commentary: coincidental metabolic syndrome increases the risk of liver fibrosis
      progression in patients with chronic hepatitis B.

PMID- 24735138
TI  - Commentary: coincidental metabolic syndrome increases the risk of liver fibrosis
      progression in patients with chronic hepatitis B - authors' reply.

PMID- 24735139
TI  - Commentary: TIPSS for Budd-Chiari syndrome.

PMID- 24735140
TI  - Commentary: TIPSS for Budd-Chiari syndrome - authors' reply.

PMID- 24735141
TI  - Commentary: metformin use is associated with reduced gastric cancer risk.

PMID- 24735142
TI  - Commentary: metformin use is associated with reduced gastric cancer risk -
      authors' reply.

PMID- 24735143
TI  - Letter: nonresponsive coeliac disease and evaluation of the strictness of a
      gluten-free diet.

PMID- 24735144
TI  - Letter: nonresponsive coeliac disease and evaluation of the strictness of a
      gluten-free diet - authors' reply.

PMID- 24735145
TI  - Letter: biological drugs for inducing remission in ulcerative colitis.

PMID- 24735146
TI  - Letter: TNFalpha blockers and psoriasis: a 'reasonable paradox' - the role of TH
      17 cells.

PMID- 24735147
TI  - Letter: biological drugs for inducing remission in ulcerative colitis - authors'
      reply.

PMID- 24735148
TI  - Letter: not the end of the role of anti-viral therapy in ulcerative colitis with
      cytomegalovirus reactivation.

PMID- 24735149
TI  - Letter: not the end of the role of anti-viral therapy in ulcerative colitis with
      cytomegalovirus reactivation - authors' reply.

PMID- 24735150
TI  - Letter: distinguishing PPI-responsive oesophageal eosinophilia from eosinophilic
      oesophagitis - still a long way to go.

PMID- 24735151
TI  - Letter: distinguishing PPI-responsive oesophageal eosinophilia from eosinophilic
      esophagitis - still a long way to go; authors' reply.

PMID- 24735152
TI  - Letter: do interferon lambda 3 polymorphisms predict the outcome of interferon
      therapy in hepatitis B infection?

PMID- 24735153
TI  - Letter: do interferon lambda 3 polymorphisms predict the outcome of interferon
      therapy in hepatitis B infection? Authors' reply.

PMID- 24735154
TI  - Association of the five-factor personality model with prefrontal activation
      during frontal lobe task performance using two-channel near-infrared
      spectroscopy.
AB  - AIM: The aim of this study was to investigate the biological background of the
      five-factor model using near-infrared spectroscopy and cognitive tasks. METHODS:
      Twenty right-handed healthy volunteers participated in this study. Their
      personality traits were assessed using the NEO Five-Factor Inventory, and changes
      in oxyhemoglobin concentration ([oxy-Hb]) were measured during cognitive tasks
      using a wireless near-infrared spectroscopy. RESULTS: The average [oxy-Hb] in the
      right prefrontal area had a significant positive correlation with the
      agreeableness score during the Stroop test at incongruent stimulus block. For the
      verbal fluency task, there were no significant correlations of bilateral [oxy-Hb]
      changes with any items. CONCLUSION: Higher agreeableness scores may involve less
      suppression to the default mode network related to resting state brain function.
      Keeping selective attention during the Stroop test may require more power of
      concentration than retrieving words during the verbal fluency task.

PMID- 24735155
TI  - Clear cell sarcoma of the kidney in a child with Fanconi anemia.
AB  - Patients with Fanconi anemia subgroup D1, attributable to biallelic mutations in
      BRCA2, have an increased risk of solid tumors. Tumors in the kidneys of these
      patients are almost exclusively Wilms tumor. We report the first recorded case,
      to our knowledge, of a Clear Cell Sarcoma of the Kidney in a patient with this
      cancer predisposition syndrome. We review different aspects of the need for
      careful clinical observation in patients of this complementation group, given
      their risk for malignancy.

PMID- 24735156
TI  - Traumatic dental injuries among 8- to 12-year-old schoolchildren in Pinggu
      District, Beijing, China, during 2012.
AB  - BACKGROUND: Although traumatic dental injuries are most common during childhood
      and can cause significant health problems, the literature contains few reports of
      the prevalence of traumatic dental injuries in children in China. AIM: To study
      the prevalence of and factors related to traumatic dental injuries among 8- to 12
      year-old schoolchildren in Pinggu District, Beijing during 2012. MATERIAL AND
      METHODS: An epidemiological survey of traumatic dental injuries was performed in
      all nine primary schools of Pinggu District, Beijing, China. Andreasen criteria
      as the diagnostic criteria were used in the study. A sample of 5165 students aged
      from 8 to 12 years old were examined, consisting of 2711 boys and 2454 girls.
      RESULTS: A total of 367 students (7.1%), 251 boys and 116 girls, were found to
      have traumatic dental injuries, and 442 permanent teeth were involved. Maxillary
      central incisors were the most affected by dental injuries (378, 85.5%). Among
      the 52 traumatized teeth (11.8%) that were treated, endodontic treatment (55.8%)
      was the most common method. CONCLUSIONS: The study showed a relatively low
      prevalence of dental injuries in Pinggu District. The treatment rate of
      traumatized teeth was relatively low. Schoolchildren need more medical assistance
      when they face accidents. Policymakers should develop a strategy for the
      prevention of traumatic dental injuries. Educational programs to increase the
      knowledge of traumatic dental injuries and prevent them should be initiated for
      teachers and schoolchildren.

PMID- 24735157
TI  - Occurrence of surface polysulfides during the interaction between ferric
      (hydr)oxides and aqueous sulfide.
AB  - Polysulfides are often referred to as key reactants in the sulfur cycle,
      especially during the interaction of ferric (hydr)oxides and sulfide, forming
      ferrous-sulphide minerals. Despite their potential relevance, the extent of
      polysulfide formation and its relevance for product formation pathways remains
      enigmatic. We applied cryogenic X-ray Photoelectron Spectroscopy and wet chemical
      analysis to study sulfur oxidation products during the reaction of goethite and
      lepidocrocite with aqueous sulfide at different initial Fe/S molar ratios under
      anoxic conditions at neutral pH. The higher reactivity of lepidocrocite leads to
      faster and higher electron turnover compared to goethite. We were able to
      demonstrate for the first time the occurrence of surface-associated polysulfides
      being the main oxidation products in the presence of both minerals, with a
      predominance of disulfide (S2(2-)(surf)), and elemental sulfur. Concentrations of
      aqueous polysulfide species were negligible (<1%). With prior sulfide fixation by
      zinc acetate, the surface-associated polysulfides could be precipitated as
      zerovalent sulfur (S degrees ), which was extracted by methanol thereafter. Of
      the generated S degrees , 20-34% were associated with S2(2-)(surf). Varying the
      Fe/S ratio revealed that surface polysulfide formation only becomes dominant when
      the remaining aqueous sulfide concentration is low (<0.03 mmol L(-1)). We
      hypothesize these novel surface sulfur species, particularly surface disulfide,
      to act as pyrite precursors. We further propose that these species play an
      overlooked role in the sulfur cycle. 

PMID- 24735159
TI  - 2013 Statistics for global prescription medications: CNS therapeutics maintain a
      leading position among small molecule therapeutics.

PMID- 24735158
TI  - Respiratory viral pathogens among Singapore military servicemen 2009-2012:
      epidemiology and clinical characteristics.
AB  - BACKGROUND: Few studies have comprehensively described tropical respiratory
      disease surveillance in military populations. There is also a lack of studies
      comparing clinical characteristics of the non-influenza pathogens with influenza
      and amongst themselves. METHODS: From May 2009 through October 2012, 7733
      consenting cases of febrile respiratory illness (FRI) (temperature [greater than
      or equal to]37.5 degrees C with cough or sorethroat) and controls in the
      Singapore military had clinical data and nasal washes collected prospectively.
      Nasal washes underwent multiplex PCR, and the analysis was limited to viral mono
      infections. RESULTS: 49% of cases tested positive for at least one virus, of whom
      10% had multiple infections. 53% of the FRI cases fulfilled the definition of
      influenza-like illness (ILI), of whom 52% were positive for at least one virus.
      The most frequent etiologies for mono-infections among FRI cases were Influenza
      A(H1N1)pdm09 (13%), Influenza B (13%) and coxsackevirus (9%). The sensitivity,
      specificity, positive predictive value and negative predictive value of ILI for
      influenza among FRI cases were 72%, 48%, 40% and 69% respectively. On logistic
      regression, there were marked differences in the prevalence of different symptoms
      and signs between viruses with fever more prevalent amongst influenza and
      adenovirus infections than other viruses. CONCLUSION: There are multiple viral
      etiologies for FRI and ILI with differing clinical symptoms in the Singapore
      military. Influenza and coxsackevirus were the most common etiology for FRI,
      while influenza and adenoviruses displayed the most febrile symptoms. Further
      studies should explore these differences and possible interventions.

PMID- 24735161
TI  - Processed foods and the nutrition transition: evidence from Asia.
AB  - This paper elucidates the role of processed foods and beverages in the 'nutrition
      transition' underway in Asia. Processed foods tend to be high in nutrients
      associated with obesity and diet-related non-communicable diseases: refined
      sugar, salt, saturated and trans-fats. This paper identifies the most significant
      'product vectors' for these nutrients and describes changes in their consumption
      in a selection of Asian countries. Sugar, salt and fat consumption from processed
      foods has plateaued in high-income countries, but has rapidly increased in the
      lower-middle and upper-middle-income countries. Relative to sugar and salt, fat
      consumption in the upper-middle- and lower-middle-income countries is converging
      most rapidly with that of high-income countries. Carbonated soft drinks, baked
      goods, and oils and fats are the most significant vectors for sugar, salt and fat
      respectively. At the regional level there appears to be convergence in
      consumption patterns of processed foods, but country-level divergences including
      high levels of consumption of oils and fats in Malaysia, and soft drinks in the
      Philippines and Thailand. This analysis suggests that more action is needed by
      policy-makers to prevent or mitigate processed food consumption. Comprehensive
      policy and regulatory approaches are most likely to be effective in achieving
      these goals. 

PMID- 24735163
TI  - Exploring spiritual needs and their associated factors in an urban sample of
      early and advanced cancer patients.
AB  - Although it is widely recognised that people turn to spirituality in times of
      crises, the interest in exploring the spiritual needs of cancer patients is just
      beginning to grow. The purpose of this study was to conduct a spiritual needs
      assessment with cancer patients living in a Northern European metropolitan region
      in order to (a) examine the relevance and nature of spiritual needs; (b) to
      clarify the role of demographic and clinical characteristics in spiritual needs;
      and (c) to identify their associations with dimensions of psychological distress.
      N = 285 outpatients with mixed cancer sites and of all tumour stages were
      surveyed cross-sectionally. Instruments included the Spiritual Needs
      Questionnaire (SpNQ) and measures of anxiety, distress, hopelessness and meaning
      related life attitudes. Almost all patients (94%) reported at least one spiritual
      need. The needs for Inner Peace and Actively Giving emerged to be of greatest
      importance. Significant, but weak differences were found for age, gender and
      being in a partnership. No associations for medical characteristics were
      observed. Regression analyses revealed anxiety as the strongest predictor for the
      subscales Existential Needs, Inner Peace and Actively Giving. The results
      emphasise the relevance of spiritual needs in cancer patients. The call for
      spiritual assessment and interventions to meet spiritual needs in cancer patients
      is strengthened. 

PMID- 24735162
TI  - Serotype Diversity of Foot-and-Mouth-Disease Virus in Livestock without History
      of Vaccination in the Far North Region of Cameroon.
AB  - Little information is available about the natural cycle of foot-and-mouth disease
      (FMD) in the absence of control measures such as vaccination. Cameroon presents a
      unique opportunity for epidemiological studies because FMD vaccination is not
      practiced. We carried out a prospective study including serological, antigenic
      and genetic aspects of FMD virus (FMDV) infections among different livestock
      production systems in the Far North of Cameroon to gain insight into the natural
      ecology of the virus. We found serological evidence of FMDV infection in over 75%
      of the animals sampled with no significant differences of prevalence observed
      among the sampled groups (i.e. market, sedentary, transboundary trade and
      mobile). We also found antibodies reactive to five of the seven FMDV serotypes
      (A, O, SAT1, SAT2 and SAT3) among the animals sampled. Finally, we were able to
      genetically characterize viruses obtained from clinical and subclinical FMD
      infections in Cameroon. Serotype O viruses grouped into two topotypes (West and
      East Africa). SAT2 viruses grouped with viruses from Central and Northern Africa,
      notably within the sublineage causing the large epidemic in Northern Africa in
      2012, suggesting a common origin for these viruses. This research will guide
      future interventions for the control of FMD such as improved diagnostics,
      guidance for vaccine formulation and epidemiological understanding in support of
      the progressive control of FMD in Cameroon. 

PMID- 24735164
TI  - Synthesis of substituted adamantylzinc reagents using a Mg-insertion in the
      presence of ZnCl2 and further functionalizations.
AB  - The LiCl-mediated Mg-insertion in the presence of ZnCl2 allows an efficient
      synthesis of adamantylzinc reagents starting from the corresponding
      functionalized tertiary bromides. The highly reactive adamantylzinc species
      readily undergo a broad variety of functionalizations such as Negishi cross
      couplings, Cu(I)-catalyzed acylations and allylations, and 1,4-addition reactions
      leading to the expected products in excellent yields. Furthermore, the adamantyl
      moiety could be introduced as alpha-substituent in terthiophene, increasing its
      solubility due to the higher lipophilicity and the prevention of pi-stacking. 

PMID- 24735165
TI  - Activity and spatial distribution of Candida antarctica lipase B immobilized on
      macroporous organic polymeric adsorbents.
AB  - A systematic study of the influence of carrier particle size (500-850 MUm) and
      enzyme load (26,200-66,100 lipase activity units (LU)/g dry carrier) on the
      content and activity of Candida antarctica lipase B (CALB) immobilized by
      adsorption onto macroporous poly(methyl methacrylate) (PMM) and polystyrene (PS)
      carriers was conducted. Furthermore, localization of CALB on the carrier was
      investigated by light and fluorescence microscopy of freeze microtome sliced
      catalyst particles. Fluorescence microscopy showed localization of enzyme in an
      outer rim of 50-85 and 10-20 MUm thickness for the PMM and PS catalysts,
      respectively, whereas no rim was observed in the absence of enzyme. Statistical
      analyses showed that carrier type was the major effect in determining the
      activities of the catalysts, with enzyme load being the second most significant
      effect and particle size also exerting a significant, yet smaller, effect. The
      PMM catalysts showed higher activities compared to PS catalysts, possibly
      indicating that the microenvironment interactions of CALB with the PMM are more
      favorable than with the PS carrier, resulting in a higher specific enzyme
      activity. Furthermore, smaller particles and higher enzyme load had a positive
      influence on the activities within the investigated ranges, and the carrier type
      and enzyme load interaction was statistically significant (p < 0.001).

PMID- 24735166
TI  - Immunomodulatory agents.

PMID- 24735167
TI  - A convergent approach to the dioxaadamantane core of (+/-)-tetrodotoxin.
AB  - A fully stereocontrolled 1,3-diol orthoesterification and a water-promoted
      intramolecular Henry addition, combined with the previously reported formal (3 +
      3) annulation of alpha-nitro-alpha,beta-enals and 2,2-dimethyl-1,3-dioxan-5-one,
      provided for a short convergent pathway to the dioxaadamantane core of (+/-)
      tetrodotoxin. 

PMID- 24735168
TI  - An interesting case of F-18 fluorodeoxyglucose positron emission tomography avid
      renal oncocytoma.

PMID- 24735169
TI  - Birth weight and cognition in children with epilepsy.
AB  - OBJECTIVE: Birth weight is an important indicator of prenatal environment, and
      subtle variations of birth weight within the normal range have been associated
      with differential risk for cognitive and behavioral problems. Therefore, we aimed
      to determine if there are differences in birth weight between full-term children
      with uncomplicated new/recent-onset epilepsies and typically developing healthy
      controls. We further examined the relationships between birth weight and
      childhood/adolescent cognition, behavior, and academic achievement. METHODS: One
      hundred eight children with new-onset/recent-onset epilepsy and 70 healthy
      controls underwent neuropsychological assessment. All participants were born full
      term (>37 weeks) without birth complications. Parents were interviewed regarding
      their child's gestation, birth, and neurodevelopmental history. RESULTS: Birth
      weight of children with epilepsy was significantly lower than healthy controls (p
      = 0.023). Whereas birth weight (covaried with age, sex, handedness, and mother's
      education) was significantly associated with cognition in controls in multiple
      domains (intelligence, language, aspects of academic achievement), this
      relationship was absent in children with epilepsy. Birth weight was not
      associated with clinical epilepsy variables (age of onset, epilepsy syndrome) and
      was not predictive of a variety of other academic or psychiatric comorbidities of
      epilepsy. SIGNIFICANCE: Although the origin of lower birth weight in children
      with epilepsy is unknown, these findings raise the possibility that abnormal
      prenatal environment may affect childhood-onset epilepsy. Furthermore, the
      positive relationship between birth weight and cognition evident in healthy
      controls was disrupted in children with epilepsy. However, birth weight was not
      related to academic and psychiatric comorbidities of childhood epilepsy. A
      PowerPoint slide summarizing this article is available for download in the
      Supporting Information section here.

PMID- 24735170
TI  - Operative factors associated with short-term outcome in horses with large colon
      volvulus: 47 cases from 2006 to 2013.
AB  - REASONS FOR PERFORMING STUDY: There is an important need for objective parameters
      that accurately predict the outcome of horses with large colon volvulus.
      OBJECTIVES: To evaluate the predictive value of a series of histomorphometric
      parameters on short-term outcome, as well as the impact of colonic resection on
      horses with large colon volvulus. STUDY DESIGN: Retrospective cohort study.
      METHODS: Adult horses admitted to the Equine and Farm Animal Veterinary Center at
      North Carolina State University, Peterson and Smith and Chino Valley Equine
      Hospitals between 2006 and 2013 that underwent an exploratory coeliotomy,
      diagnosed with large colon volvulus of >=360 degrees, where a pelvic flexure
      biopsy was obtained, and that recovered from general anaesthesia, were selected
      for inclusion in the study. Logistic regression was used to determine
      associations between signalment, histomorphometric measurements of interstitium
      to-crypt ratio, degree of haemorrhage, percentage loss of luminal and glandular
      epithelium, as well as colonic resection with short-term outcome (discharge from
      the hospital). RESULTS: Pelvic flexure biopsies from 47 horses with large colon
      volvulus were evaluated. Factors that were significantly associated with short
      term outcome on univariate logistic regression were Thoroughbred breed (P =
      0.04), interstitium-to-crypt ratio >1 (P = 0.02) and haemorrhage score >=3 (P =
      0.005). Resection (P = 0.92) was not found to be associated significantly with
      short-term outcome. No combined factors increased the likelihood of death in
      forward stepwise logistic regression modelling. A digitally quantified
      measurement of haemorrhage area strengthened the association of haemorrhage with
      nonsurvival in cases of large colon volvulus. CONCLUSIONS: Histomorphometric
      measurements of interstitium-to-crypt ratio and degree of haemorrhage predict
      short-term outcome in cases of large colon volvulus. Resection was not associated
      with short-term outcome in horses selected for this study. Accurate
      quantification of mucosal haemorrhage at the time of surgery may improve
      veterinary surgeons' prognostic capabilities in horses with large colon volvulus.

PMID- 24735172
TI  - Gender differences in support for the discontinuation of female genital cutting
      in Sierra Leone.
AB  - Despite decades of policies, interventions and legislation, many girls and women
      are being subjected to female genital cutting (FGC) across the African continent.
      Because FGC has profound implications for women's wellbeing and reproductive
      health rights, an examination of behavioural changes toward the practice is
      imperative to reinforce strategies directed at eradicating it. Using a nationally
      representative survey, this study examines support for discontinuation of FGC and
      its associated predictors among both women and men in Sierra Leone. Findings
      reveal gender differences in attitudes toward the elimination of the practice
      across most of the socioeconomic predictors. Interestingly, beliefs about and
      perceived benefits of FGC emerge as important determinants of the support for the
      elimination of FGC, both genders considered. The findings highlight the
      importance of achieving gender equality and women's empowerment, and the
      necessity for a more contextualised approach to FGC eradication. 

PMID- 24735171
TI  - A comparison of adverse reaction rates for PAS C versus plasma platelet units.
AB  - BACKGROUND: Plasma constituents have been implicated in some types of platelet
      (PLT) transfusion reactions. Leukoreduced apheresis PLTs stored in InterSol have
      65% less plasma than apheresis PLTs stored in 100% plasma (PPs). This study
      compared transfusion reaction rates in InterSol PLTs (PLT additive solution [PAS]
      C) versus PPs. STUDY DESIGN AND METHODS: The study design was an open-label,
      nonrandomized retrospective review. Statistical methods were applied to
      substantiate noninferiority and superiority of PAS C compared to PP in terms of
      transfusion reaction rates. Adverse reactions (ARs) were categorized using the
      Biovigilance Component of the National Healthcare Safety Network. Active
      surveillance was used to monitor all transfusions, both with ARs and without ARs.
      RESULTS: A total of 14,005 transfusions from six study sites were included, with
      9845 PP transfusions given to 2202 patients and 4160 PAS C to 1444 patients. A
      total of 165 ARs were reported. Percentages of transfusions with ARs were 1.37%
      for PPs, 0.55% for PAS C, and 1.13% overall. The relative risk (RR) for PAS C
      versus PPs was calculated as 0.403 with an upper confidence limit (UCL) of 0.663.
      Overall, ARs with the highest incidence were allergic transfusion reactions
      (ATRs) and febrile nonhemolytic transfusion reactions (FNHTRs), at 0.66 and 0.40%
      of total transfusions reported, respectively. The relative risks (UCLs) for ATRs
      and FNHTRs, respectively, were 0.350 (0.686) and 0.336 (0.827). CONCLUSIONS: PAS
      C PLTs were statistically superior and noninferior to PPs with respect to the
      transfusion-related AR rate. PAS C noninferiority and superiority were also
      demonstrated for ATRs and FNHTRs, separately.

PMID- 24735173
TI  - Characterization of CTX-M-producing Escherichia coli by repetitive sequence-based
      PCR and real-time PCR-based replicon typing of CTX-M-15 plasmids.
AB  - The emergence of extended-spectrum beta-lactamase (ESBL)-producing
      Enterobacteriaceae is a major global concern. CTX-M is the dominating ESBL type
      worldwide, and CTX-M-15 is the most widespread CTX-M type. The dissemination of
      CTX-M appears to be in part due to global spread of the Escherichia coli clone
      O25b-ST131. However, the gene-encoding CTX-M is mainly located on mobile genetic
      elements, such as plasmids, that also promote the horizontal dissemination of the
      CTX-M genes. In this study, 152 CTX-M-producing E. coli isolated in 1999-2008 in
      Orebro County, Sweden, were typed using a commercial repetitive sequence-based
      PCR (the DiversiLab system), and the prevalence of ST131 was investigated by pabB
      PCR. Real-time PCR-based plasmid replicon typing was performed on 82 CTX-M-15
      producing E. coli isolates. In general, the CTX-M-producing E. coli population
      was genetically diverse; however, ST131 was highly prevalent (27%), and the
      dominating clone in our area. The blaCTX -M-15 gene was mainly located on IncF
      plasmids (69%), but a relatively high proportion of IncI1 plasmids (29%) were
      also detected among E. coli with diverse rep-PCR patterns, indicating that
      horizontal transmission of IncI1 plasmids carrying blaCTX -M-15 may have occurred
      between different E. coli strains. 

PMID- 24735174
TI  - Hemodynamic monitoring of middle cerebral arteries during cognitive tasks
      performance.
AB  - AIM: The aim of this study was to obtain temporal pattern and hemispheric
      dominance of blood flow velocity (BFV) changes and to assess suitability of
      different cognitive tasks for monitoring of BFV changes in the middle cerebral
      arteries (MCA). METHODS: BFV were recorded simultaneously in MCA during
      performance of phonemic verbal fluency test (pVFT), Trail Making Tests A and B
      (TMTA and TMTB) and Stroop tests in 14 healthy, right-handed volunteers aged 20
      26 years. RESULTS: A significant increase of BFV in both MCA was obtained during
      performance of all cognitive tasks. Statistically significant lateralization was
      found during performance of Stroop test with incongruent stimuli, while TMTB was
      found to have the best activation potential for MCA. CONCLUSION: Our findings
      specify TMTB as the most suitable cognitive test for monitoring of BFV in MCA.

PMID- 24735175
TI  - Increased serum level of N-terminal Pro-B-type natriuretic peptide as a possible
      biomarker of cardiovascular risk in psoriatic patients.
AB  - BACKGROUND: Apparently, these days psoriasis is regarded as a systemic disease
      with frequent cardiovascular comorbidities, such as hypertension, myocardial
      infarction, valvular defects etc., which may lead to reduced lifespan or even
      sudden death. Therefore, it is important that biomarkers helpful in early
      detection or prediction of cardiovascular complications as well as their
      prevention should be identified. Even though the N-terminal pro B-type
      natriuretic peptide (NT-proBNP) is a well-known cardiovascular predictor in
      cardiovascular (CV) patients and in the general population, its usefulness in
      detection of CV comorbidities in psoriatic patients is still unclear. OBJECTIVE:
      The aim of the study was to determine whether the N-terminal pro B-type
      natriuretic peptide (NT-proBNP) concentration was increased in psoriatic
      patients. METHODS: The study included 73 psoriatic patients and 45 age-matched
      healthy individuals. The serum NT pro-BNP concentration as well as lipid profile
      parameters were assessed in the study and control groups. Correlations between
      patients' clinical data, their serum NT-proBNP and lipid concentrations were
      calculated. RESULTS: The serum concentration of NT-proBNP was significantly
      higher in psoriatic patients (109.22 +/- 172.59 pg/mL) in comparison with
      controls (35.82 +/- 22.90 pg/mL) (P = 0.000054). In 28 (38.36%) psoriatic
      patients the lipid profile was within normal limits, whereas in 45 (61.64%)
      psoriatic patients triglyceride and/or total cholesterol were increased.
      Moreover, in both psoriatic groups, i.e. normo- and hyperlipidaemic, NT-proBNP
      concentrations were significantly higher compared to normo- and hyperlipidaemic
      controls, P = 0.02 and P = 0.001 respectively. A positive correlation was found
      between the NT-proBNP concentration and duration of psoriasis (P < 0.05).
      CONCLUSIONS: The study findings confirmed higher NT-proBNP concentrations in
      psoriatic patients, which could be a useful biomarker of CV disease in both normo
      and hyperlipidaemic groups.

PMID- 24735176
TI  - A GFP promoter fusion library for the study of Salmonella biofilm formation and
      the mode of action of biofilm inhibitors.
AB  - Salmonella, an important foodborne pathogen, forms biofilms in many different
      environments. The composition of these biofilms differs depending on the growth
      conditions, and their development is highly coordinated in time. To develop
      efficient treatments, it is therefore essential that biofilm formation and its
      inhibition be understood in different environments and in a time-dependent
      manner. Many currently used techniques, such as transcriptomics or proteomics,
      are still expensive and thus limited in their application. Therefore, a GFP
      promoter fusion library with 79 important Salmonella biofilm genes was developed
      (covering among other things matrix production, fimbriae and flagella synthesis,
      and c-di-GMP regulation). This library is a fast, inexpensive, and easy-to-use
      tool, and can therefore be conducted in different experimental setups in a time
      dependent manner. In this paper, four possible applications are highlighted to
      illustrate and validate the use of this reporter fusion library.

PMID- 24735177
TI  - Development and preliminary assessment of a critical care ultrasound course in an
      adult pulmonary and critical care fellowship program.
AB  - BACKGROUND: The focused ultrasound examination has become increasingly recognized
      as a safe and valuable diagnostic tool for the bedside assessment of the
      critically ill patient. We implemented a dedicated on-site critical care
      ultrasonography curriculum with the goal of developing a model for teaching
      ultrasound skills to pulmonary and critical care medicine fellows. METHODS: The
      program was comprised of blended didactic and bedside sessions in the following
      topic domains: fundamentals; vascular access and diagnosis; and abdominal,
      thoracic, and cardiac ultrasonography. Formal knowledge and image acquisition
      assessments were performed before and after the program to assess success in
      meeting predefined learning objectives. Participants completed surveys (on Likert
      scale 1-5) before and after the program to assess their confidence in
      ultrasonography knowledge and skills as well as their perception as to training
      effectiveness. RESULTS: The preintervention knowledge and bedside image
      acquisition scores were 71 and 32%, respectively. The global preintervention
      score was 51%. All postintervention measures demonstrated significant
      improvement: 89% (P < 0.01), 86% (P < 0.0001), and 87% (P < 0.0001).
      Preintervention participant confidence in their ultrasound knowledge and skill
      was 2.9/5, which improved to 4.3/5 (P = 0.007) after intervention. Participants
      rated the curriculum as meeting course objectives at a mean of 4.8/5.
      CONCLUSIONS: At one academic medical center, the knowledge of eight adult
      pulmonary and critical care fellowship trainees regarding critical care
      ultrasound was high at baseline; however, bedside image acquisition skills were
      poor. A dedicated 6-week educational intervention resulted in highly significant
      improvements in subject knowledge and image acquisition skills. These preliminary
      results warrant validation studies at other medical centers.

PMID- 24735178
TI  - Sequential and spatial organization of metal complexes inside a peptide duplex.
AB  - To generate integrated organized molecular properties, multiple molecular
      components are required to be assembled into the molecular system with sequential
      and spatial accuracy in accordance with the design of the molecular assembly.
      Herein, we present a novel programmable synthesis of a cofacially stacked
      porphyrin array via repetitive construction of a peptide duplex. We designed and
      synthesized a novel porphyrin having two artificial amino acid moieties at the
      trans meso-positions. The amino acid moieties can be connected with another
      porphyrin unit by repetitive doubly coupling reactions to afford the peptide
      duplex bridged by the porphyrins. In the duplex, the porphyrin units are stacked
      cofacially, and the efficient electronic communication among the arrayed
      porphyrin units was characterized by split redox waves in the cyclic
      voltammograms. We also demonstrated the three different square-planar metal ions,
      namely Cu(2+), Ni(2+), and Pd(2+), were arranged inside the ladder-type porphyrin
      array in a programmable fashion. 

PMID- 24735179
TI  - Association between 17q12-21 variants and asthma in Japanese women: rs11650680
      polymorphism as potential genetic marker for asthma.
AB  - Epidemiological evidence on the relationship between single-nucleotide
      polymorphisms (SNPs) rs7216389 and rs11650680 on chromosome 17q12-21 and asthma
      is inconsistent. We examined this issue in young adult Japanese women. Case
      subjects were 202 women who had been diagnosed with asthma by a doctor, while
      1290 women without doctor-diagnosed asthma served as control subjects.
      Adjustments were made for age and the presence of older siblings. There were no
      significant associations between SNP rs7216389 and asthma. Compared with the CC
      genotype of SNP rs11650680, the CT genotype, but not the TT genotype, was
      significantly inversely associated with asthma: the adjusted odds ratio for the
      CT genotype was 0.67 (95% confidence interval: 0.46-0.96). This inverse
      relationship was significant in women with late-onset asthma, but not in those
      with early-onset asthma. Under the dominant model, a significant inverse
      association was found between rs11650680 and asthma in women without older
      siblings, but not in those with older siblings; the interaction, however, was not
      significant. This is the first study to show that the CT genotype of SNP
      rs11650680 was significantly inversely associated with asthma, especially adult
      onset asthma. We could not find evidence for interactions between rs11650680 and
      older siblings affecting asthma. 

PMID- 24735180
TI  - Situation-specific factors predicting nonadherence to methadone maintenance
      treatment: a cross-sectional study using the case-crossover design in Guangzhou,
      China.
AB  - Methadone maintenance treatment (MMT) is a key risk reduction measure for
      controlling HIV transmission among drug users. Studies using traditional methods
      exist to distinguish between drop outs and nondrop outs. However, many nondrop
      outs use MMT discontinuously and no study has identified situation-specific
      factors predicting their showing or not showing up. This study used a case
      crossover design comparing situation-specific factors appearing on the last
      episode of attendance versus those of the last episode of nonattendance. A total
      of 133 participants were recruited from two MMT clinics in Guangzhou, China.
      Participants were asked separately whether various situation-specific factors
      existed in the last episodes of nonattendance and attendance of MMT. Matched odds
      ratios (ORs) based on conditional logistic regression analysis were presented.
      The results showed that the participants attended the MMT clinics on average for
      25 days in the last month. Situation-specific factors significantly predicting
      nonattendance included: (1) physical and mental health status: in illness (OR =
      33.0, P < 0.001), in a bad mood (OR = 7.5, P < 0.001), and occurrence of an
      unhappy event (OR = 18.0, P < 0.001); (2) other engagement: work engagement (OR =
      40.0, P < 0.001), trip to other places (OR = 83.0, P < 0.001), and social
      activities (OR = 10.0, P = 0.012); (3) interpersonal relationship: conflicts with
      family (OR = 19.0, P = 0.004); and (4) structural situational factors: financial
      difficulty (OR = 19.0, P = 0.004) and worrying about police arrest (OR = 12.0, P
      = 0.003). Other factors such as interaction with drug users and heroin use were
      marginally significant, while reduced methadone dosage was nonsignificant.
      Interventions to improve MMT adherence need to consider situation-specific
      factors. Ancillary psychosocial services should be integrated with current MMT;
      MMT should also provide more flexible services to the clients. Furthermore,
      efforts should be taken to build up interdisciplinary teams and to connect with
      MMT in order to provide holistic harm reduction, rehabilitation, and health care.

PMID- 24735181
TI  - Defects in laterality with emphasis on heterotaxy syndromes with asplenia and
      polysplenia: an autopsy case series at a single institution.
AB  - Heterotaxy is a rare disease with high morbidity and mortality. Controversy
      exists over how to classify these syndromes with most cases stratified into
      asplenia/polysplenia syndromes or right/left isomerism. In an effort to review
      comprehensively specific pheonotypes associated with heterotaxy syndromes, we
      reviewed published cases series, adopted a classification scheme based on spleen
      status, and evaluated autopsy cases retrospectively with abnormal laterality at
      our institution. We categorized 116 cases as situs inversus totalis, polysplenia,
      asplenia, and single right-sided spleen. Cardiovascular abnormalities occurred in
      87.1% of polysplenia, 90.5% of asplenia, and all cases of single right-sided
      spleen. For polysplenia, 48.9% had bilateral bilobed lungs, 87% had right-sided
      stomach, 58.1% had midline symmetric liver, and 60.4% had malrotated intestines.
      For asplenia, 51.9% had bilateral trilobed lungs, 86.7% had right-sided stomach,
      45.8% had symmetric liver, and 65.5% had malrotated intestines. Atrioventricular
      septal defects occurred in 91.2% of asplenia compared to 56.8% of polysplenia
      cases. Eight percent had pulmonary/aortic stenosis or atresia. Double outlet
      right ventricle was more common in polysplenia (32.6%) compared to asplenia
      (21.4%). Total anomalous systemic venous return was described in 55.6% of
      polysplenia and total anomalous pulmonary venous connections in 81% of asplenia
      cases. Greater than half of the cases had no heterotaxy diagnosis. Although, we
      found similar heterotaxy-associated characteristics, the frequencies differed
      from previous studies. We found great variation in how heterotaxy-associated
      defects were described, diagnosed, and reported. Although there are known
      associated characteristics with the polysplenia/asplenia syndromes, correct
      identification requires a standardized approach for diagnosis and reporting.

PMID- 24735182
TI  - How effective is eccentric viewing training? A systematic literature review.
AB  - PURPOSE: The global prevalence of age-related macular degeneration and associated
      central vision loss is rising. Central vision loss hinders the performance of
      many activities of daily living. Adaptive strategies such as eccentric viewing
      and steady eye strategy may be used to compensate for central vision loss. In
      order to establish the potential of these rehabilitation strategies, this
      systematic review evaluates current literature regarding the effectiveness of
      eccentric viewing and steady eye strategy training in people with central vision
      loss. RESULTS: The search strategies identified 2605 publications, 36 of which
      met the inclusion criteria for the review, but only three of which were
      randomised controlled trials. This literature shows that eccentric viewing and
      steady eye strategy training can improve near visual acuity, reading speed, and
      performance of activities of daily living in people with central vision loss.
      However, there was insufficient literature to establish a relationship between
      training and distance visual acuity or quality of life. There is no conclusive
      evidence to show that a particular model of eccentric viewing training is
      superior to another, little clear evidence of a relationship between participant
      characteristics and training outcomes and no data regarding the cost
      effectiveness of training. CONCLUSION: This report highlights the need for
      further robust research to establish the true potential and cost effectiveness of
      eccentric viewing and steady eye strategy training as a rehabilitation strategy
      for individuals with central vision loss.

PMID- 24735183
TI  - Macrolide, lincosamide, and streptogramin B resistance in lipophilic
      Corynebacteria inhabiting healthy human skin.
AB  - Corynebacteria exist as part of human skin microbiota. However, under some
      circumstances, they can cause opportunistic infections. The subject of the study
      was to examine the macrolide-lincosamide-streptogramin B (MLSB) antibiotic
      resistance in 99 lipophilic strains of Corynebacterium genus isolated from the
      skin of healthy men. Over 70% of the tested strains were resistant to
      erythromycin and clindamycin. All of which demonstrated a constitutive type of
      MLSB resistance mechanism. In all strains, there were being investigated the
      erm(A), erm(B), erm(C), erm(X), lin(A), msr(A), and mph(C) genes that could be
      responsible for the different types of resistance to marcolides, lincosamides,
      and streptogramin B. In all strains with the MLSB resistance phenotype, the
      erm(X) gene was detected. None of the other tested genes were discovered. Strains
      harboring the erm(X) gene were identified using a phenotypic method based on
      numerous biological and biochemical tests. Identification of the chosen strains
      was compared with the results of API Coryne, MALDI-TOF MS, and 16S rDNA
      sequencing methods. Only 7 out of the 23 investigated resistant strains provided
      successful results in all the used methods, showing that identification of this
      group of bacteria is still a great challenge. The MLSB resistance mechanism was
      common in most frequently isolated from healthy human skin Corynebacterium
      tuberculostearicum and Corynebacterium jeikeium strains. This represents a threat
      as these species are also commonly described as etiological factors of
      opportunistic infections. 

PMID- 24735185
TI  - Study on the Distribution of Disease-Resistant Shrimp Identified by DNA Markers
      in Respect to WSSV Infection in Different Seasons Along the Entire East Coast of
      India Aiming to Prevent White Spot Disease in Penaeus monodon.
AB  - White spot disease caused by white spot syndrome virus (WSSV) is responsible for
      harming shrimp aquaculture industry and results in a pandemic throughout the
      world. Undeniably, the knowledge on geographic distribution, transmission,
      virulence, and seasonal prevalence of this disease alongside information on the
      distribution of disease-resistant shrimps may be helpful to understand important
      aspects of disease biology. This study was intended to estimate WSSV prevalence
      by qualitative and quantitative PCR method among the Penaeus monodon samples
      collected from four different places namely Digha, West Bengal; Chilika, Orissa;
      Visakhapatnam, Andhra Pradesh; and Chennai, Tamil Nadu at three different seasons
      in the period of 2011-2013 from east coast of India. Along with this, the disease
      resistant prevalence was also investigated using earlier developed 71 bp
      microsatellite and 457 bp RAPD-SCAR DNA marker among the collected shrimps.
      Qualitative PCR depicted that the cumulative WSSV prevalence at four places was
      the lowest (0%) at pre-monsoon, whereas, it was the highest (21.2%) during post
      monsoon season. Quantitative real-time PCR showed the average copy number of WSSV
      to be the highest (~10(3) copy MUg(-1) shrimp genomic DNA) at post-monsoon
      season. Additionally, estimated disease-resistant prevalence was the highest in
      Visakhapatnam (79%) and lowest in Digha (21%). It is well known to all that a
      trait cannot be identified using a single genetic pattern. This study will
      significantly contribute insight to develop specific pathogen-resistant (SPR)
      seeds of P. monodon simultaneously using two DNA markers that would be a cost
      effective and safer approach towards disease prevention instead of conventional
      trends of seed generation from unselected wild broodstock.

PMID- 24735184
TI  - Bleeding patterns during the menopausal transition in the multi-ethnic Study of
      Women's Health Across the Nation (SWAN): a prospective cohort study.
AB  - OBJECTIVE: Previous studies describing menses duration and heaviness of flow
      during the menopausal transition (MT) have been short in duration and limited to
      white women. We estimated the frequency of and risk factors for prolonged
      bleeding, spotting and heavy bleeding during the MT in an ethnically diverse
      population. DESIGN: Prospective community-based cohort study. SETTING USA:
      southeastern Michigan, northern California and Los Angeles, California.
      POPULATION: A total of 1320 midlife women who participated in the Study of
      Women's Health Across the Nation (SWAN) Menstrual Calendar Substudy. Participants
      included African-American, white, Chinese, and Japanese women. METHODS: Women
      completed daily menstrual calendars from 1996 to 2006, and provided information
      on hormone therapy, smoking and physical activity. Annual measures included
      height and weight. Kaplan-Meier survival analysis and multivariable regression
      were used to analyse the data. MAIN OUTCOME MEASURES: Menses of 10+ days,
      spotting of 6+ days, heavy bleeding of 3+ days. RESULTS: At least three
      occurrences of menses 10+ days was reported by 77.7% (95% confidence interval
      [95% CI] 56.7-93.2), of 6+ days of spotting by 66.8% (95% CI 55.2-78.0) and of 3+
      days of heavy bleeding by 34.5% (95% CI 30.2-39.2) of women. Menses of 10+ days,
      6+ days of spotting, and 3+ days of heavy bleeding were associated with MT stage,
      uterine fibroids, hormone use and ethnicity. Body mass index was associated with
      3+ days of heavy bleeding. CONCLUSIONS: These data provide clinicians and women
      with important information about the expected frequency of prolonged and heavy
      bleeding and spotting during the menopausal transition that may facilitate
      clinical decision making.

PMID- 24735187
TI  - Disordered gambling in residential substance use treatment centers: an unmet
      need.
AB  - This study examined prevalence and potential impact of disordered gambling in a
      sample of individuals (N = 684) undergoing residential treatment for substance
      use disorders at 13 facilities. Lifetime disordered gambling prevalence was
      20.2%, as identified by South Oaks Gambling Screen. Within individuals who
      screened positive for disordered gambling, few had sought help for gambling
      (15.9%) and only 14.3% reported having gambling addressed in their current
      substance use disorder treatment. Meanwhile, 30.4% identified gambling as a
      concern in their recovery efforts. The presence of a gambling problem, either
      historical or current, potentially affects residential treatment outcomes and
      warrants clinical attention within these programs. 

PMID- 24735186
TI  - Multi-dimensional factors associated with unprotected anal intercourse with
      regular partners among Chinese men who have sex with men in Hong Kong: a
      respondent-driven sampling survey.
AB  - BACKGROUND: The HIV prevalence and incidence among men who have sex with men
      (MSM) are high. Unprotected anal intercourse (UAI) with male regular partners
      (RP) is an important but under-emphasized risk behavior. The current study aimed
      to describe the prevalence of UAI with regular partner and the associated multi
      dimensional factors with UAI among MSM in Hong Kong, China. METHODS: Respondent
      Driven Sampling method was used to recruit participants. A total of 285
      participants were recruited, of whom 211 (75.1%) had had anal sex with RP in the
      last six months and their data were analyzed in this report. Weighed data were
      presented and logistic regression methods were fit. RESULTS: Participants' high
      risk behaviors in the last six months included high prevalence of having had UAI
      with RP (45.8%), having had non-regular male sex partners (NRP: 27.3%) and UAI
      with such partners (18.9%). Adjusted for socio-demographic variables, factors
      associated with UAI with RP included: 1) substances use prior to having anal sex
      (65.7% versus 43.8%; AOR =2.36; 95% CI =1.07-5.18), 2) worry that condom use
      symbolizes mistrust (67.9% versus 44.3%; AOR = 2.91; 95% CI =1.19-7.10), 3) a
      lower perceived degree of the RP's acceptance of condom use (91.7% versus 38.3%;
      AOR = 22.70; 95% CI =6.20-83.10), and 4) a higher level of impulsivity (61.1%
      versus 35.0%; AOR =4.02; 95% CI = 1.62-9.97). Two of these four variables,
      substances use (ORm = 2.28, 95% CI = 1.01-5.16) and perceived lower level of RP's
      acceptance of condom use (ORm = 17.22; 95% CI = 5.06-58.62) were selected by the
      forward stepwise logistic regression model. CONCLUSIONS: MSM with RP in Hong Kong
      is subjected to high risk of HIV transmission. Risk factors of UAI are multi
      dimensional and interventions need to take into account factors of structural,
      interpersonal and individual levels.

PMID- 24735188
TI  - Warning color changes in response to food deprivation in the pipevine swallowtail
      butterfly, Battus philenor.
AB  - Predation on distasteful animals should favor warning coloration that is
      relatively conspicuous and phenotypically invariable. However, even among
      similarly colored individuals there can be variation in their warning signals. In
      butterflies, individual differences in larval feeding history could cause this
      variation. The warning signal of the pipevine swallowtail butterfly, Battus
      philenor L. (Lepidoptera: Papilionidae) consists of both a blue iridescent patch
      and pigmentbased orange spots on the ventral hindwing. B. philenor males also
      display a dorsal surface iridescent patch that functions as a sexual indicator
      signal. A previous study of iridescence in B. philenor found that the iridescent
      blue on both the dorsal and ventral hind wings is variable and significantly
      different between lab-reared and field-caught individuals. These differences
      could be the result of larval food deprivation in the field. Through experimental
      manipulation of larval diet, larval food deprivation was evaluated as a potential
      cause of the differences observed between lab and field individuals, and if food
      deprivation is a source of inter-individual variation in warning signals. B.
      philenor larvae were food restricted starting at two points in the last larval
      instar, and one group was fed through pupation. Adult coloration was then
      compared. Food deprivation led to poorer adult condition, as indicated by lower
      adult body mass, forewing length, and fat content of stressed individuals. As the
      level of food deprivation increased, the hue of the iridescent patches on both
      the dorsal and ventral hind wing shifted to shorter wavelengths, and the chroma
      of the orange spots decreased. The shifts in iridescent color did not match the
      differences previously found between lab and field individuals. However, the
      treatment differences indicate that food deprivation may be a significant source
      of warning color variation. The differences between the treatment groups are
      likely detectable by predators, but the effect of the variation on signal
      effectiveness and function remains to be empirically explored.

PMID- 24735189
TI  - Formations of hydroxyapatite and inositol hexakisphosphate in poultry litter
      during the composting period: sequential fractionation, P K-edge XANES and
      solution (31)P NMR investigations.
AB  - Little is known about how the solubility and chemical speciation of phosphorus
      (P) in poultry litters are altered during the composting period. This study
      investigated the quantitative and qualitative changes in organic P (Po) and
      inorganic P (Pi) compositions in poultry litters during the seven-day composting
      period using sequential extraction in combination with P K-edge X-ray absorption
      near-edge structure (XANES) and solution (31)P nuclear magnetic resonance (NMR)
      spectroscopy. The result of sequential extraction illustrated that the
      significant decrease of H2O-P by 55% in poultry litters occurred concomitantly
      with the increase of HCl-Pi and HCl-Po during the composting period (p < 0.05). X
      ray diffraction results for poultry litter samples showed three distinct peaks
      indicative of hydroxyapatite. Phosphorus K-edge XANES confirmed the increase of
      hydroxyapatite during the composting period, corresponding to the increase of HCl
      Pi determined by the sequential extraction. The NaOH-EDTA extraction for solution
      (31)P NMR revealed that myo-inositol hexakisphosphate (IHP) constituted about 80%
      of phosphate monoesters and was increased from 16 to 28% in the poultry litter
      during the composting period. The combined applications of chemical extraction
      and molecular-spectroscopic techniques determined that water-soluble P in poultry
      litter was transformed into less soluble phases, primarily hydroxyapatite and
      IHP, during the composting period. 

PMID- 24735191
TI  - Graphene oxide nanosheet wrapped white-emissive conjugated polymer nanoparticles.
AB  - We have demonstrated the preparation of white-emissive conjugated polymer
      nanoparticles wrapped with graphene oxide (GO) nanosheets. Highly stable, GO
      wrapped, poly(9,9-di-n-octylfluorenyl-2,7-diyl) nanoparticles (GO-PFO NPs) with
      diameters in the range 30-150 nm were successfully obtained by utilizing the GO
      nanosheets as an interface stabilizer in an emulsification process. The
      synthesized GO-PFO NPs exhibited unique white-emitting photoluminescence with a
      characteristic green-emissive broad band above 500 nm, which was distinct from
      the photoluminescent behavior of PFO NPs without GO. This green emission was
      deduced to originate from the presence of the GO nanosheet shell surrounding the
      PFO NPs, rather than from luminescence of GO itself or formation of keto defects
      in the PFO chain. PL decay analysis showed that the GO-wrapped PFO NPs had a
      longer luminescence lifetime in comparison to PFO NPs without GO, and highly
      efficient energy transfer to lower energy state induced by the GO occurred. 

PMID- 24735190
TI  - Sedative and mechanical hypoalgesic effects of butorphanol in xylazine
      premedicated donkeys.
AB  - REASONS FOR PERFORMING STUDY: Combinations of alpha2 -adrenoceptor and opioid
      agonists are commonly used in equids, but little scientific information is
      available on donkeys. OBJECTIVES: To compare the sedative and hypoalgesic effects
      of xylazine alone or in combination with different dosages of butorphanol in
      donkeys. STUDY DESIGN: Placebo-controlled, operator-blinded, randomised,
      crossover, Latin square study. METHODS: Six donkeys received intravenous normal
      saline and normal saline (NS-NS); xylazine (0.5 mg/kg bwt) and normal saline (X
      NS); xylazine and 10 MUg/kg bwt butorphanol (X-B10); xylazine and 20 MUg/kg bwt
      butorphanol (X-B20); xylazine and 30 MUg/kg bwt butorphanol (X-B30); and xylazine
      and 40 MUg/kg bwt butorphanol (X-B40). Sedation scores (SS), head height above
      ground (HHAG) and mechanical nociceptive thresholds (MNT) were assessed before
      and for 120 min after treatment. Areas under the curve (AUC) values for 0-30, 30
      60 and 60-120 min were computed for SS, HHAG and MNT. As appropriate, differences
      between treatments were analysed using the Friedman test followed by Dunn's test
      and a repeated measures one-way analysis of variance followed by Tukey's test;
      significance was set at P<0.05. RESULTS: All treatments apart from NS-NS induced
      sedation. Butorphanol treatments induced significantly larger SS-AUC0 -30 values
      than those for NS-NS (P<0.05). Compared to corresponding NS-NS values, HHAG-AUC0 
      30 values were significantly smaller for all other treatments (P<0.001) and HHAG
      AUC30-60 values were significantly smaller for X-B40 (P<0.05). Compared to NS-NS,
      all treatments induced mechanical hypoalgesia and yielded significantly larger
      MNT-AUC0-30 values (P<0.001). Treatment X-NS yielded significantly smaller MNT
      AUC0 -30 values than those for X-B30 and X-B40 (P<0.05). Only MNT-AUC30 -60
      values for X-B30 and X-B40 were significantly larger than those for NS-NS and X
      NS (P<0.05). CONCLUSIONS: Sedation and mechanical hypoalgesia induced by xylazine
      were enhanced by butorphanol at 40 MUg/kg bwt. This drug combination may be
      suitable for chemical restraint of donkeys undergoing certain clinical
      procedures.

PMID- 24735192
TI  - Copper-catalyzed oxoazidation and alkoxyazidation of indoles.
AB  - Copper-catalyzed oxoazidation and alkoxyazidation of indoles has been developed.
      The dearomatization reaction which leads to versatile 3-azido indolenine and
      oxindole derivatives in moderate to good yields could be used in a further
      transformation. 

PMID- 24735193
TI  - Posterior mediastinal paraspinal angioleiomyoma causing thoracic radiculopathy.

PMID- 24735194
TI  - Randomized study of washing 40- to 42-day-stored red blood cells.
AB  - BACKGROUND: Pretransfusion washing of red blood cells (RBCs) stored for a longer
      duration may have theoretical advantages but few data exist to support this
      practice. In many hospital settings, use of a point-of-care cell washer could
      conceivably be used to quickly wash allogeneic RBCs before transfusion. The
      purpose of this preliminary study was to compare a point-of-care device with a
      common blood bank device for washing longer-stored RBCs. STUDY DESIGN AND
      METHODS: Forty RBC units stored for 40 to 42 days were randomized to washing with
      the COBE 2991 device (Terumo BCT; FDA-cleared for washing stored RBCs) or the
      Cell Saver Elite (Haemonetics; FDA-cleared point-of-care device for processing
      and washing fresh autologous shed whole blood). Supernatant and unit RBCs from
      unwashed (baseline) and washed blood were assayed for potassium, lactate,
      intracellular ATP, percentage of RBC recovery, cell-free hemoglobin, RBC
      microparticles, and RBCs were examined for susceptibility to hemolysis by
      physical stress. RESULTS: Both devices recovered a high percentage of RBCs and
      efficiently removed extracelluar potassium. Washing with the Elite resulted in
      significant increases in cell-free Hb, percent hemolysis, and RBC microparticle
      production, whereas washing with the COBE 2991 did not (fold Delta = 2.1 vs. 1.0,
      4.6 vs. 1.2, 2.0 vs. 1.1, respectively; p < 0.05). Hemolysis induced by physical
      stress was not altered by washing. CONCLUSION: Although point-of-care washing of
      longer-stored RBCs is appealing, these preliminary data suggest that transfusion
      of washed, longer-stored units could result in potentially greater exposure to
      plasma free Hb. More data are needed before this practice can be routinely
      recommended.

PMID- 24735195
TI  - Periorbital papules and erythematous-brownish plaques on the neck and axilla.

PMID- 24735196
TI  - Ethics in global health outreach: three key considerations for pharmacists.
AB  - OBJECTIVE: The objective of this article is to explore three key ethical tenets
      that pharmacists should consider prior to participating in global health
      outreach. KEY FINDINGS: There are increasing opportunities for pharmacists to be
      involved in global health outreach; however, little attention has been given to
      the ethical issues that participation may raise for pharmacists. Pharmacists'
      widely accepted and basic ethical obligations at home lay the foundation for
      effective management of these ethical challenges abroad. At home, pharmacists
      have an ethical obligation to provide the best possible quality of care to the
      patients for whom they serve. During global health outreach, this involves
      identifying and mitigating the potential for harm, as well as understanding and
      respecting cultural differences. Furthermore, pharmacists have an ethical
      obligation to not only meet individual patient needs, but also community and
      societal needs, when applicable. In global health outreach, this involves
      tailoring interventions to the needs of the population served. CONCLUSIONS:
      Because of their unique skillset, pharmacists have the potential to make
      significant contributions to global health. Applying ethical principles, such as
      providing the best possible care, respecting cultural differences and meeting
      societal needs, provides the foundation for successful global health outreach by
      pharmacists.

PMID- 24735197
TI  - Copper-catalyzed intramolecular tandem reaction of (2-halogenphenyl)(3
      phenyloxiran-2-yl)methanones: synthesis of (Z)-aurones.
AB  - A convenient and efficient method for the copper-catalyzed synthesis of (Z)
      aurones via intramolecular tandem reaction of (2-halogenphenyl)(3-phenyloxiran-2
      yl)methanones is reported. Moreover, a plausible mechanism for the formation of
      (Z)-aurones is proposed. This is the first report on the synthesis of (Z)-aurones
      through copper-catalyzed Ullmann coupling reaction employing epoxides as
      substrates. 

PMID- 24735198
TI  - Primary subcutaneous spindle cell Ewing sarcoma with strong S100 expression and
      EWSR1-FLI1 fusion: a case report.
AB  - Ewing sarcoma is described classically as a small, round cell tumor of bone and
      soft tissue in children and young adults. Ewing sarcoma most often is
      characterized by a fusion of the Ewing sarcoma breakpoint region 1 (EWSR1) and
      the Friend leukemia virus integration 1 (FLI1) genes, forming an EWSR1-FLI1
      fusion transcript. We report an exceptional case of primary subcutaneous Ewing
      sarcoma in a 16-year-old female composed entirely of spindle cells with focal
      fascicular growth and exhibiting strong, diffuse immunohistochemical reactivity
      for S100, unlike classic Ewing sarcoma. However, reverse transcription-polymerase
      chain reaction (RT-PCR) analysis confirmed the presence of a rare variant of the
      EWSR1-FLI1 fusion transcript, featuring fusion of EWSR1 exon 10 to FLI1 exon 6.
      To our knowledge, the combined histologic, molecular, and clinical features have
      not been reported previously in Ewing sarcoma, and raise a broad differential
      diagnosis emphasizing the importance of molecular techniques in the diagnosis of
      this tumor.

PMID- 24735199
TI  - Can a woman refuse sex if her husband has a sexually transmitted infection?
      Attitudes toward safer-sex negotiation among married women in Bangladesh.
AB  - In developing countries, HIV, sexually transmitted infections (STIs) and
      unintended pregnancy take an enormous toll on women's reproductive health, yet
      preventive programmes are lacking as married women's risks are frequently
      underestimated. We examined predictors of married Bangladeshi women's attitudes
      towards safer-sex negotiation using data on 15,178 currently married women aged
      15-49 from the 2011 Bangladesh Demographic Health Survey. Approximately 92% of
      women believed that a wife's refusal to have sex with her husband is justified if
      he has an STI. Multilevel logistic regression analysis revealed that the
      likelihood of a woman holding this belief increased with her autonomy, as
      measured by the ability to go to a health centre/hospital without another adult,
      participation in household decision making and rejection of wife beating (p <
      0.001). Other significant predictors were knowledge/awareness of STIs (p < 0.05),
      living in Dhaka division (p < 0.001) and younger age (p < 0.01). Our findings
      suggest that sexual health education programmes may be more effective if they
      include strategies to address social norms and cultural practices that limit
      women's autonomy in society. 

PMID- 24735200
TI  - Epilepsy surgery and meaningful improvements in quality of life: results from a
      randomized controlled trial.
AB  - OBJECTIVE: We examine improvement and worsening in quality of life (QOL) in terms
      of proportions achieving minimum clinically important change (MCID), and factors
      related to MCID, in patients with temporal lobe epilepsy randomized to medical or
      surgical treatment. METHODS: Eighty patients with temporal lobe epilepsy
      randomized to surgical (n(1) = 40) or medical (n(2) = 40) therapy were followed
      for 12 months, reporting QOL at baseline, and at 6 and 12 months. Previously
      established thresholds for MCID across various general and epilepsy-specific QOL
      instruments were used to determine meaningful improvement (positive MCID) or
      worsening (negative MCID). Generalized linear mixed-effects models were used to
      compare MCID in both groups. RESULTS: At 6 months, 56.0% of patients in the
      surgical group achieved positive MCID on the Quality of Life in Epilepsy (QOLIE)
      89, as compared to 11.0% of those in the medical group (p < 0.001). On the QOLIE
      31, 62.0% of the surgical group and 17.0% of the medical group achieved positive
      MCID (p < 0.001). Substantially more medically treated patients exhibited
      clinically significant worsening in QOL, as compared with those surgically
      treated. The respective medical versus surgical proportions with worsening were
      36.67% versus 13.8% in QOLIE31, 20% versus 15% in Health Utility Index-III (HUI
      III), and 30% versus 19% in Short Form-36 (SF-36) Mental Composite Score (MCS).
      The number of patients who need to undergo surgery for one additional person to
      have a meaningful improvement in the QOLIE-31 is two (number needed to treat =
      2). The results also favored surgery using the generic HUI-III instrument, but
      not with the mental of physical function subscales of the SF-36. SIGNIFICANCE:
      Significantly more patients in the surgical group achieved meaningful improvement
      in epilepsy-specific measures of QOL at 6 and 12 months compared to those in the
      medical group. Substantially more patients in the medical therapy group exhibited
      clinically significant worsening in their QOL assessed with epilepsy-specific and
      generic instruments. A PowerPoint slide summarizing this article is available for
      download in the Supporting Information section here.

PMID- 24735201
TI  - Family quality of life in families affected by HIV: the perspective of HIV
      positive mothers.
AB  - The HIV infection of a family member can impact family quality of life (FQoL).
      The objectives of this study are to (1) describe patterns of FQoL among mothers
      living with HIV (MLHIV) and (2) identify key factors associated with FQoL in
      families affected by HIV. Recruitment took place in HIV-specialized clinics and
      community organizations. A 100 MLHIV and 67 of their children participated in
      this study. Mothers were on average 40.8 years old and reported having an average
      of two dependent children at home (M = 2.1, SD = 1.0). Participating children
      were 16.2 years old, on average. Half of the children were boys (50.8%). More
      than half were aware of their mother's positive HIV status (68.2%) and 19.7% were
      diagnosed with HIV. All HIV-positive children were aware of their status. A
      latent profile analysis was performed on the five continuous indicators of FQoL,
      and three main profiles of self-reported FQoL among MLHIV were established: high
      FQoL (33%), moderate FQoL (58%), and low FQoL (9%). Among the mothers'
      characteristics, education, physical functioning, social support, and resilience
      increased FQoL, while anxiety and irritability decreased FQoL. Among the
      children's characteristics, resilience followed the FQoL profile. A trend was
      observed toward children's greater awareness of the mother's HIV status in high
      and low FQoL profiles. Additionally, irritability tended to be higher within the
      lower FQoL profile. FQoL profiles can be used to identify families needing
      special care, particularly for family interventions with both parents and
      children. Other relevant indicators must be studied (e.g., closeness and support
      between family members, availability and accessibility of care, family structure,
      father-child relationships, and medical condition of the mother) and longitudinal
      research conducted to estimate the direction of causality between FQoL profile
      and individual family member characteristics. 

PMID- 24735202
TI  - Autophagy mediates neutrophil responses to bacterial infection.
AB  - Neutrophils constitute the first line of cellular defense against pathogens and
      autophagy is a fundamental cellular homeostasis pathway that operates with the
      intracellular degradation/recycling system. Induction of the autophagic process
      in neutrophils, in response to invading pathogens, constitutes a crucial
      mechanism in innate immunity. Exploration of autophagy has greatly progressed and
      diverse strategies have been reported for studying this molecular process in
      different biological systems; especially in infectious and inflammatory diseases.
      Furthermore, the role of autophagy in neutrophils, during pathogenic infection,
      continues to be of interest, due to the role of the cell in immunity function,
      its recruitment to the site of infection and its implication in inflammatory
      diseases. This review focuses on the known role of autophagy in neutrophils
      defence against pathogenic infections. A more detailed discussion will concern
      the recent findings highlighting the role of autophagy in inflammation and cell
      death in infected neutrophils. 

PMID- 24735203
TI  - Methodological challenges in studies of bright light therapy to treat sleep
      disorders in nursing home residents with dementia.
AB  - AIM: Numerous studies have explored the effectiveness of bright light therapy as
      a treatment of sleep disorders in nursing home and long-stay geriatric hospital
      residents, most of whom have dementia. A recent Cochrane Collaboration meta
      analysis of 10 selected studies concluded that there was insufficient evidence to
      assess its therapeutic efficacy as most available studies had methodological
      problems. We sought to remedy this situation by developing proposals to guide
      research methods in future studies. METHODS: Based on the literature and our own
      clinical and research experience, we developed a series of proposals relating to
      study design, participant selection, light delivery modalities and outcome
      measures that we believe will maximize the chances of identifying a bright light
      treatment effect. We then checked adherence to these proposals in all relevant
      published experimental studies. RESULTS: Of the 18 studies published in the last
      two decades that met our selection criteria, only half the studies had selected
      participants with a sleep disorder. Eleven studies excluded people with severe
      vision loss; seven included a clinical rating of sleep, and five measured
      baseline lighting levels. Most checked psychoactive medication prescriptions but
      few reported changes in prescriptions over the course of the study. Most also
      checked treatment adherence and included some control for differences in amount
      of social contact. CONCLUSIONS: Evidence for the effectiveness of bright white
      light treatment in people residing in nursing homes is equivocal. We anticipate
      that the quality of this evidence will be improved if researchers refine their
      study methods and adopt a more uniform approach.

PMID- 24735204
TI  - FGF21 increases cholesterol efflux by upregulating ABCA1 through the ERK1/2
      PPARgamma-LXRalpha pathway in THP1 macrophage-derived foam cells.
AB  - FGF21, a member of the fibroblast growth factor superfamily, is an important
      endogenous regulator of systemic glucose and lipid metabolism. Elevated serum
      FGF21 levels have been reported in subjects with coronary heart disease and
      carotid artery plaques. However, whether FGF21 is associated with atherosclerotic
      diseases remains unclear. In this study, the effects of FGF21 on cholesterol
      efflux in THP1 macrophage-derived foam cells and the underlying mechanisms were
      investigated. THP1 macrophage-derived foam cells were incubated with 0, 25, 50,
      100, 200, and 400 ng/mL of FGF21 for varying time periods (0, 6, 12, and 24 h).
      Cholesterol efflux onto apoA-1 was assessed by high-performance liquid
      chromatography assays, while change in ABCA1 expression was analyzed by western
      blot and real-time quantitative PCR. Incubation was performed with the ERK1/2
      specific inhibitor PD98059, PPARgamma-specific inhibitor GW9662, and LXRalpha
      siRNA. Our results show that FGF21 promotes cholesterol efflux and ABCA1
      expression in THP1 macrophage-derived foam cells in a dose- and time-dependent
      manner. In addition, inhibition of ERK1/2 or PPARgamma, or knockdown of LXRalpha
      attenuated FGF21-mediated promotion of ABCA1 expression and cholesterol efflux.
      These results demonstrate that FGF21 can promote cholesterol efflux by
      upregulating ABCA1 through the ERK1/2-PPARgamma-LXRalpha pathway in THP1
      macrophage-derived foam cells. 

PMID- 24735205
TI  - Improved efficiency of bulk heterojunction polymer solar cells by doping low
      bandgap small molecules.
AB  - We present performance improved ternary bulk heterojunction polymer solar cells
      by doping a small molecule, 2,4-bis[4-(N,N-diisobutylamino)-2,6-dihydroxyphenyl]
      squaraine (DIB-SQ), into the common binary blend of poly(3-hexylthiophene) (P3HT)
      and [6,6]-phenyl-C71-butyric acid methyl ester (PC71BM). The optimized power
      conversion efficiency (PCE) of P3HT:PC71BM-based cells was improved from 3.05% to
      3.72% by doping 1.2 wt % DIB-SQ as the second electron donor, which corresponds
      to ~22% PCE enhancement. The main contributions of doping DIB-SQ material on the
      improved performance of PSCs can be summarized as (i) harvesting more photons in
      the low-energy range, (ii) increased exciton dissociation, energy transfer, and
      charge carrier transport in the ternary blend films. The energy transfer process
      from P3HT to DIB-SQ is demonstrated by time-resolved transient photoluminescence
      spectra through monitoring the lifetime of 700 nm emission from neat P3HT, DIB-SQ
      and blended P3HT:DIB-SQ solutions. The lifetime of 700 nm emission is increased
      from 0.9 ns for neat P3HT solution, to 4.9 ns for neat DIB-SQ solution, to 6.2 ns
      for P3HT:DIB-SQ blend solution. 

PMID- 24735207
TI  - Association between socioeconomic vulnerability and height with obesity in low
      income Chilean children in the transition from preschool to first grade.
AB  - This study determined the percentage of obesity among lower-income Chilean
      children 4-6 years of age, by socioeconomic vulnerability (family score assessing
      the children's risk of becoming poor) and height. The sample included 17,080
      children with anthropometry at 4, 5, and 6 years of age, and three categories of
      socioeconomic vulnerability. Body mass index Z-score (BMI Z), % obesity,
      height/age Z-score (HAZ) by socioeconomic vulnerability/sex, the effect of
      socioeconomic vulnerability on BMI Z and HAZ by age/sex, and BMI Z and % obesity
      at 4-6 years, according to initial height, were determined. Between 4-6 years, %
      obesity is very high, especially among the less-vulnerable and taller children.
      Preventive measures should prioritize this group. 

PMID- 24735206
TI  - Identification of transcription factors and single nucleotide polymorphisms of
      Lrh1 and its homologous genes in Lrh1-knockout pancreas of mice.
AB  - BACKGROUND: To identify transcription factors (TFs) and single nucleotide
      polymorphisms (SNPs) of Lrh1 (also named Nr5a2) and its homologous genes in Lrh1
      knockout pancreas of mice. METHODS: The RNA-Seq data GSE34030 were downloaded
      from Gene Expression Omnibus (GEO) database, including 2 Lrh1 pancreas knockout
      samples and 2 wild type samples. All reads were processed through TopHat and
      Cufflinks package to calculate gene-expression level. Then, the differentially
      expressed genes (DEGs) were identified via non-parametric algorithm (NOISeq)
      methods in R package, of which the homology genes of Lrh1 were identified via
      BLASTN analysis. Furthermore, the TFs of Lrh1 and its homologous genes were
      selected based on TRANSFAC database. Additionally, the SNPs were analyzed via SAM
      tool to record the locations of mutant sites. RESULTS: Total 15683 DEGs were
      identified, of which 23 was Lrh1 homology genes (3 up-regulated and 20 down
      regulated). Fetoprotein TF (FTF) was the only TF of Lrh1 identified and the
      promoter-binding factor of FTF was CYP7A. The SNP annotations of Lrh1 homologous
      genes showed that 92% of the mutation sites were occurred in intron and upstream.
      Three SNPs of Lrh1 were located in intron, while 1819 SNPs of Phkb were located
      in intron and 1343 SNPs were located in the upstream region. CONCLUSION: FTF
      combined with CYP7A might play an important role in Lrh1 regulated pancreas
      specific transcriptional network. Furthermore, the SNPs analysis of Lrh1 and its
      homology genes provided the candidate mutant sites that might affect the Lrh1
      related production and secretion of pancreatic fluid.

PMID- 24735208
TI  - Body mass index and blood pressure among men of three ethnic groups of
      Darjeeling, West Bengal, India.
AB  - This study was undertaken from 2009-2011 to understand the association between
      body mass index (BMI) and blood pressure (BP) (systolic or SBP and diastolic or
      DBP) among randomly chosen men, aged 30 to 59 years, of three endogamous
      communities in Darjeeling, West Bengal, India: Dhimal (n = 88), Mech (n = 71),
      and Rajbanshi (n = 83). Analysis of variance was applied. Remarkable rates of BMI
      based undernutrition (chronic energy deficiency or CED) were recorded among
      Dhimals (31%) and Rajbanshis (18%). Notable prevalence of overweight (20%) was
      recorded among men of Mech community. None were found to be obese in three
      samples. Mean SBP and DBP were found to rise consistently at levels of BMI
      (undernutrition, normal, and overweight). BMI was observed to rise consistently
      at levels of blood pressures (normotensive, prehypertensive, and hypertensive).
      Among Mech, this pattern was found to be more conspicuous. DBP was found to be
      more sensitive with changes of BMI in men. 

PMID- 24735209
TI  - Migration as a turning point in food habits: the early phase of dietary
      acculturation among women from South Asian, African, and Middle Eastern Countries
      living in Norway.
AB  - This article explores the early phase of dietary acculturation after migration.
      South Asian, African and Middle Eastern women (N = 21) living in Norway were
      interviewed about their early experiences with food in a new context. The
      findings pointed to abrupt changes in food habits in the first period after
      migration. To various degrees, women reported unfamiliarity with foods in shops,
      uncertainty about meal formats and food preparation and fear of eating food
      prohibited by their religion. Their food consumption tended to be restricted to
      food items perceived as familiar or safe. Our findings indicate that the first
      period after migration represents a specific phase in the process of dietary
      acculturation. Early initiatives aimed at enhancing confidence in food and
      familiarity with the new food culture are recommended. 

PMID- 24735210
TI  - Effects of information on young consumers' willingness to pay for genetically
      modified food: experimental auction analysis.
AB  - This study examines the effects of information on consumers' willingness to pay
      (WTP) for genetically modified food (GMF). We used Vickrey second price
      experimental auction method for elicitation of consumer WTP for GM potato chips
      and GM soya-chocolate bar. The sample used in this study was university students
      from Delhi, India. Four information formats (positive, negative, no information,
      and combined information about GM technology) were used for the examination. The
      results show that, when students received the combine information they were
      willing to pay around 17%-20% premium for GMF and when received the negative
      information they demanded around 22% discount for GMF. While the positive- and
      the no-information formats alone have no considerable effect on consumers' WTP
      for GMF. Overall, our findings suggest that while doing marketing of GMF in
      India, the best strategy is to provide combined information about GM technology. 

PMID- 24735211
TI  - Household food insecurity shows associations with food intake, social support
      utilization and dietary change among refugee adult caregivers resettled in the
      United States.
AB  - Forced migration puts families at risk of household food insecurity and economic
      hardship. We administered a questionnaire to examine household food insecurity in
      a sample of 49 recently legally resettled Sudanese refugees with at least one
      child under age 3 years. Of households polled, 37% had experienced household food
      insecurity and 12% reported child hunger within the previous month. Increasing
      severity of household food insecurity was associated with decreased consumption
      of high-cost, high-nutrient-density food items and increased consumption of some
      low-cost traditional Sudanese foods by adult caregivers of young children.
      Furthermore, household food insecurity was associated with decreased household
      and per capita food expenditure, indicators of more limited dietary change with
      migration, and indicators of increased social support. 

PMID- 24735212
TI  - A case study of middle school food policy and persisting barriers to healthful
      eating.
AB  - Decreasing access to competitive foods in schools has produced only modest
      effects on adolescents' eating patterns. This qualitative case study investigated
      persistent barriers to healthful eating among students attending an ethnically
      diverse middle school in a working-class urban neighborhood that had banned on
      campus competitive food sales. Participant observations, semi-structured
      interviews and document reviews were conducted. Unappealing school lunches and
      easily accessible unhealthful foods, combined with peer and family influences,
      increased the appeal of unhealthy foods. Areas for further inquiry into
      strategies to improve urban middle school students' school and neighborhood food
      environments are discussed. 

PMID- 24735213
TI  - In silico prediction of chemical acute oral toxicity using multi-classification
      methods.
AB  - Chemical acute oral toxicity is an important end point in drug design and
      environmental risk assessment. However, it is difficult to determine by
      experiments, and in silico methods are hence developed as an alternative. In this
      study, a comprehensive data set containing 12, 204 diverse compounds with median
      lethal dose (LD50) was compiled. These chemicals were classified into four
      categories, namely categories I, II, III and IV, based on the criterion of the
      U.S. Environmental Protection Agency (EPA). Then several multiclassification
      models were developed using five machine learning methods, including support
      vector machine (SVM), C4.5 decision tree (C4.5), random forest (RF), kappa
      nearest neighbor (kNN), and naive Bayes (NB) algorithms, along with MACCS and FP4
      fingerprints. One-against-one (OAO) and binary tree (BT) strategies were employed
      for SVM multiclassification. Performances were measured by two external
      validation sets containing 1678 and 375 chemicals, separately. The overall
      accuracy of the MACCS-SVM(OAO) model was 83.0% and 89.9% for external validation
      sets I and II, respectively, which showed reliable predictive accuracy for each
      class. In addition, some representative substructures responsible for acute oral
      toxicity were identified using information gain and substructure frequency
      analysis methods, which might be very helpful for further study to avoid the
      toxicity.

PMID- 24735214
TI  - Transposable element 'roo' attaches to nuclear matrix of the Drosophila
      melanogaster.
AB  - The genome of eukaryotes is organized into structural units of chromatin loops.
      This higher order organization is supported by a nuclear skeleton called the
      nuclear matrix. The genomic DNA associated with the nuclear matrix is called the
      matrix associated region (MAR). Only a few genome-wide screens have been
      attempted, although many studies have characterized locusspecific MAR DNA
      sequences. In this study, a MAR DNA library was prepared from the Drosophila
      melanogaster Meigen (Diptera: Drosophilidae) genome. One of the sequences
      identified as a MAR was from a long terminal repeat region of 'roo'
      retrotransposon (roo MAR). Sequence analysis of roo MAR showed its distribution
      across the D. melanogaster genome. roo MAR also showed high sequence similarity
      with a previously identified MAR in Drosophila, namely the 'gypsy'
      retrotransposon. Analysis of the genes flanking roo MAR insertions in the
      Drosophila genome showed that genes were co-ordinately expressed. The results
      from the present study in D. melanogaster suggest this sequence plays an
      important role in genome organization and function. The findings point to an
      evolutionary role of retrotransposons in shaping the genomic architecture of
      eukaryotes.

PMID- 24735216
TI  - Academic writing for publication--how to start and proceed?

PMID- 24735215
TI  - Identification and characterization of Argonaute gene family and meiosis-enriched
      Argonaute during sporogenesis in maize.
AB  - Argonaute (AGO) proteins play a key role in regulation of gene expression through
      small RNA-directed RNA cleavage and translational repression, and are essential
      for multiple developmental processes. In the present study, 17 AGO genes of maize
      (Zea mays L., ZmAGOs) were identified using a Hidden Markov Model and validated
      by rapid amplification of cDNA ends assay. Subsequently, quantitative PCR
      revealed that expressions of these genes were higher in reproductive than in
      vegetative tissues. AGOs presented five temporal and spatial expression patterns,
      which were likely modulated by DNA methylation, 5'-untranslated exons and
      microRNA-mediated feedback loops. Intriguingly, ZmAGO18b was highly expressed in
      tassels during meiosis. Furthermore, in situ hybridization and immunofluorescence
      showed that ZmAGO18b was enriched in the tapetum and germ cells in meiotic
      anthers. We hypothesized that ZmAGOs are highly expressed in reproductive
      tissues, and that ZmAGO18b is a tapetum and germ cell-specific member of the AGO
      family in maize.

PMID- 24735217
TI  - Change in smoking status during two consecutive pregnancies: a population-based
      cohort study.
AB  - OBJECTIVE: To investigate changes in tobacco smoking in two consecutive
      pregnancies and factors associated with the change. DESIGN: Population-based
      cohort study. SETTING: New South Wales, Australia, 2000-10. POPULATION: A total
      of 183,385 women having first and second singleton pregnancies. METHODS:
      Descriptive and multivariable logistic regression analyses of perinatal data
      linked to hospital admission data. MAIN OUTCOME MEASURES: Proportion of women
      smoking during their first pregnancy who quit by their second, and of women not
      smoking in their first pregnancy who did smoke during their second. RESULTS:
      Among 22,761 smokers in the first pregnancy, 33.5% had quit by their second.
      Among 160,624 non-smokers in their first pregnancy, 3.6% smoked during their
      second. Women who were aged >=25 years, were married, born in a non-English
      speaking country, used private obstetric care, and lived in a socio-economically
      advantaged area were more likely to quit or less likely to start smoking in the
      second pregnancy. Smokers who had gestational hypertension (adjusted odds ratio
      [OR] 1.36, 95% confidence interval [95% CI] 1.23-1.51), a large-for-gestational
      age infant (OR 1.66, 95% CI, 1.46-1.89), and a stillbirth (OR 1.44, 95% CI 1.06
      1.94) were more likely to quit, whereas smokers whose infant was small-for
      gestational-age (OR 0.65, 95% CI 0.60-0.70) or admitted to special care nursery
      (OR 0.87, 95% CI 0.81-0.94) were less likely to quit. Among non-smokers in the
      first pregnancy, the risk of smoking in the second pregnancy increased with late
      antenatal attendance (e.g. >=26 weeks, OR 1.30, 95% CI 1.14-1.48), gestational
      diabetes (OR 1.25, 95% CI 1.07-1.45), preterm birth (e.g. spontaneous, OR 1.25,
      95% CI 1.10-1.43), caesarean section (e.g. prelabour, OR 1.13, 95% CI 1.01-1.26),
      and infant small-for-gestational-age (OR 1.37, 95% CI 1.26-1.48) or required
      special care nursery (OR 1.14, 95% CI 1.06-1.23). Inter-pregnancy interval of >=3
      years was associated with either change in smoking status. CONCLUSIONS: Most
      smokers continue to smoke in their next pregnancy, even among those who
      experienced poor outcomes. Intensive interventions should be explored and offered
      to women at the highest risk.

PMID- 24735218
TI  - Microbial tailoring of acyl peptidic siderophores.
AB  - Marine bacteria produce an abundance of suites of acylated siderophores
      characterized by a unique, species-dependent headgroup that binds iron(III) and
      one of a series of fatty acid appendages. Marinobacter sp. DS40M6 produces a
      suite of seven acylated marinobactins, with fatty acids ranging from saturated
      and unsaturated C12-C18 fatty acids. In the present study, we report that in the
      late log phase of growth, the fatty acids are hydrolyzed by an amide hydrolase
      producing the peptidic marinobactin headgroup. Halomonas aquamarina str. DS40M3,
      another marine bacterium isolated originally from the same sample of open ocean
      water as Marinobacter sp. DS40M6, produces the acyl aquachelins, also as a suite
      composed of a peptidic headgroup distinct from that of the marinobactins. In
      contrast to the acyl marinobactins, hydrolysis of the suite of acyl aquachelins
      is not detected, even when H. aquamarina str. DS40M3 is grown into the stationary
      phase. The Marinobacter cell-free extract containing the acyl amide hydrolase is
      active toward exogenous acyl-peptidic siderophores (e.g., aquachelin C,
      loihichelin C, as well as octanoyl homoserine lactone used in quorum sensing).
      Further, when H. aquamarina str. DS40M3 is cultured together with Marinobacter
      sp. DS40M6, the fatty acids of both suites of siderophores are hydrolyzed, and
      the aquachelin headgroup is also produced. The present study demonstrates that
      coculturing bacteria leads to metabolically tailored metabolites compared to
      growth in a single pure culture, which is interesting given the importance of
      siderophore-mediated iron acquisition for bacterial growth and that Marinobacter
      sp. DS40M6 and H. aquamarina str. DS40M3 were isolated from the same sample of
      seawater.

PMID- 24735219
TI  - Prevalence of and risk factors for equine obesity in Great Britain based on owner
      reported body condition scores.
AB  - REASONS FOR PERFORMING THE STUDY: Few data are available on the prevalence of
      obesity in the general equine population of Great Britain (GB), and its
      associated risk factors. OBJECTIVES: To estimate the prevalence of owner-reported
      obesity in veterinary-registered horses and ponies in GB, and identify factors
      associated with obesity. STUDY DESIGN: A cross-sectional survey of horse/pony
      owners in GB was undertaken using a postal questionnaire. METHODS: Thirty
      veterinary practices randomly selected horse/pony owners to complete a self
      administered postal questionnaire. Owners estimated body condition score using a
      modified Carroll and Huntington method (1-6 scale), and animals were classified
      as obese if they were scored as either 5 (fat) or 6 (very fat). Factors
      associated with obesity were assessed using logistic regression analysis.
      RESULTS: Prevalence of obesity was 31.2% (n = 247/792; 95% confidence interval
      [CI] 27.9-34.2%). Factors associated with increased odds of obesity were breed
      (P<0.001), ease of maintaining weight (P<0.001) and primary use (P = 0.002).
      Compared to Thoroughbreds, draught-type (odds ratio [OR] 7.3; 95% CI 3.1-17.1),
      cob-type (OR 5.6; 95% CI 2.5-12.5), native (OR 3.2; 95% CI 1.8-5.78) and Welsh
      breeds (OR 3.5; 95% CI 1.9-6.2) were more likely to be obese. Animals described
      as 'good doers' were more likely to be obese than those described as readily
      maintaining normal weight (OR 3.7; 95% CI 2.6-5.3). Compared to competition
      animals, animals used for pleasure riding (OR 2.5; 95% CI 1.4-4.4) and nonridden
      animals (OR 2.9; 95% CI 1.5-5.5) were more likely to be obese. CONCLUSIONS:
      Identification of at-risk breeds and other horse- and management-level risk
      factors for obesity will enable optimal targeting of owner education regarding
      management strategies to reduce the frequency of equine obesity.

PMID- 24735221
TI  - Sequence-specific Cu(II)-dependent peptide bond hydrolysis: similarities and
      differences with the Ni(II)-dependent reaction.
AB  - Potentiometry and UV-vis and circular dichroism spectroscopies were applied to
      characterize Cu(II) coordination to the Ac-GASRHWKFL-NH2 peptide. Using HPLC and
      ESI-MS, we demonstrated that Cu(II) ions cause selective hydrolysis of the Ala
      Ser peptide bond in this peptide and characterized the pH and temperature
      dependence of the reaction. We found that Cu(II)-dependent hydrolysis occurs
      solely in 4N complexes, in which the equatorial coordination positions of the
      Cu(II) ion are saturated by peptide donor atoms, namely, the pyridine-like
      nitrogen of the His imidazole ring and three preceding peptide bond nitrogens.
      Analysis of the reaction products led to the conclusion that Cu(II)-dependent
      hydrolysis proceeds according to the mechanism demonstrated previously for Ni(II)
      ions (Kopera, E.; Krezel, A.; Protas, A. M.; Belczyk, A.; Bonna, A.; Wyslouch
      Cieszynska, A.; Poznanski, J.; Bal, W. Inorg. Chem. 2010, 49, 6636-6645).
      However, the pseudo-first-order reaction rate found for Cu(II) is, on average,
      100 times lower than that for Ni(II) ions. The greater ability of Cu(II) ions to
      form 4N complexes at lower pH partially compensates for this difference in rates,
      resulting in similar hydrolytic activities for the two ions around pH 7.

PMID- 24735222
TI  - Favored composition design and atomic structure characterization for ternary Al
      Cu-Y metallic glasses via proposed interatomic potential.
AB  - A realistic interatomic potential is constructed for the Al-Cu-Y system under a
      newly proposed formulism and applied to perform atomistic simulations, leading to
      predicting a hexagonal composition region within which metallic glass formation
      is energetically favored and the region is defined as the quantitative glass
      formation ability of the system. Amorphization driving force of a glassy alloy is
      then calculated to correlate the readiness of its forming ability in practice,
      and a local optimized stoichiometry is pinpointed to be Al74Cu14Y12, of which the
      metallic glass could be most stable or easiest obtainable. The predictions are
      well supported by the experimental observations reported so far in the
      literature. Further structural analysis indicates that adding Y extends the short
      range landscape and facilitates developing a hybridized icosahedral- and fcc-like
      packing in the medium-range, eventually enhancing the glass formation ability of
      the system. 

PMID- 24735223
TI  - A case of leucocyte chimerism (78,XX/78,XY) in a dog with a disorder of sexual
      development.
AB  - A 1-year-old Shih Tzu dog was presented for examination because of abnormal
      external genitalia. A residual penis with a prepuce was located in a position
      typical of a male. The dog had no palpable testicles or scrotum. The ultrasound
      examination revealed the presence of the prostate, but the gonads remained
      undetectable. Cytogenetic analysis performed on chromosome preparations obtained
      from lymphocyte culture showed two cell lines - 78,XX and 78,XY. Molecular
      analysis of 14 polymorphic microsatellite markers allowed us to distinguish
      leucocyte chimerism from whole body chimerism. The presence of 3 or 4 alleles was
      confirmed in DNA isolated from blood, while in DNA isolated from hair follicles
      only 1 or 2 alleles were detected. The case was classified as leucocyte
      78,XX/78,XY chimerism. Our study showed that XX/XY leucocyte chimerism might be
      associated with disorder of sexual development in dogs. Furthermore, it is
      emphasized that the use of cytogenetic study, in combination with analysis of
      polymorphic markers in DNA isolated from different somatic cells, facilitates
      distinguishing between leucocyte and whole body chimerism. 

PMID- 24735224
TI  - Motivation and readiness for drug treatment: differences by modality and special
      populations.
AB  - The purpose of this research is to expand our knowledge of motivational factors
      among admissions to various substance abuse treatment modalities and among those
      entering special programs. Differences in motivation are reported in a
      convenience sample of more than 6,000 admissions to 38 programs. Results from
      multilevel analyses show (a) an ordered increase in motivation by settings from
      referral to outpatient, to methadone maintenance, and to the highest levels in
      residential programs and (b) significantly lower motivation among admissions to
      programs for special populations. Results are discussed in relation to the demand
      characteristics of treatment and non-recovery reasons for entering treatment. 

PMID- 24735220
TI  - Molecular players involved in temperature-dependent sex determination and sex
      differentiation in Teleost fish.
AB  - The molecular mechanisms that underlie sex determination and differentiation are
      conserved and diversified. In fish species, temperature-dependent sex
      determination and differentiation seem to be ubiquitous and molecular players
      involved in these mechanisms may be conserved. Although how the ambient
      temperature transduces signals to the undifferentiated gonads remains to be
      elucidated, the genes downstream in the sex differentiation pathway are shared
      between sex-determining mechanisms. In this paper, we review recent advances on
      the molecular players that participate in the sex determination and
      differentiation in fish species, by putting emphasis on temperature-dependent sex
      determination and differentiation, which include temperature-dependent sex
      determination and genetic sex determination plus temperature effects. Application
      of temperature-dependent sex differentiation in farmed fish and the consequences
      of temperature-induced sex reversal are discussed. 

PMID- 24735225
TI  - How context dependent are species interactions?
AB  - The net effects of interspecific species interactions on individuals and
      populations vary in both sign (-, 0, +) and magnitude (strong to weak).
      Interaction outcomes are context-dependent when the sign and/or magnitude change
      as a function of the biotic or abiotic context. While context dependency appears
      to be common, its distribution in nature is poorly described. Here, we used meta
      analysis to quantify variation in species interaction outcomes (competition,
      mutualism, or predation) for 247 published articles. Contrary to our
      expectations, variation in the magnitude of effect sizes did not differ among
      species interactions, and while mutualism was most likely to change sign across
      contexts (and predation least likely), mutualism did not strongly differ from
      competition. Both the magnitude and sign of species interactions varied the most
      along spatial and abiotic gradients, and least as a function of the
      presence/absence of a third species. However, the degree of context dependency
      across these context types was not consistent among mutualism, competition and
      predation studies. Surprisingly, study location and ecosystem type varied in the
      degree of context dependency, with laboratory studies showing the highest
      variation in outcomes. We urge that studying context dependency per se, rather
      than focusing only on mean outcomes, can provide a general method for describing
      patterns of variation in nature.

PMID- 24735226
TI  - Treatment of hereditary angioedema: a review (CME).
AB  - Hereditary angioedema (HAE) is a rare autosomal dominant disorder characterized
      by recurrent attacks of self-limiting tissue swelling. The management of HAE has
      transformed dramatically with recently approved therapies in the United States.
      However, there is lack of awareness among physicians about these new modalities.
      The aim of this review is to update the practicing physician about various
      therapeutic options available for HAE patients. An exhaustive literature search
      of PubMed and OVID was performed to develop this article. Management of HAE is
      traditionally classified into treatment of acute attacks or on-demand therapy,
      short-term (preprocedural) prophylaxis, and long-term prophylaxis. Newer
      therapies include C1 esterase inhibitor (C1-INH) and contact system modulators,
      namely, ecallantide and icatibant. Recombinant C1-INH, which is available in
      Europe, is awaiting approval in the United States. C1-INH concentrate is approved
      for prophylaxis as well as on-demand therapy while ecallantide and icatibant are
      approved for acute treatment only. Effective HAE management further includes
      patient education, reliable access to specific medications, and regular follow-up
      to monitor therapeutic response and safety. 

PMID- 24735228
TI  - Self-care behaviour for minor symptoms: can Andersen's Behavioral Model of Health
      Services Use help us to understand it?
AB  - OBJECTIVE: To explore whether Andersen's Behavioral Model of Health Services Use
      can aid understanding of self-care behaviour and inform development of
      interventions to promote self-care for minor illness. METHOD: Qualitative
      interviews were conducted with 24 Scottish participants about their experience
      and management of minor symptoms normally associated with analgesic use.
      Synthesised data from the interviews were mapped onto the Behavioral Model. KEY
      FINDINGS: All factors identified as influencing decisions about how to manage the
      symptoms discussed, mapped onto at least one domain of Andersen's model.
      Individual characteristics including beliefs, need factors and available
      resources were associated with health behaviour, including self-care. Outcomes
      such as perceived health status and consumer satisfaction from previous
      experience of managing symptoms also appeared to feed back into health behaviour.
      CONCLUSIONS: The Behavioral Model seems relevant to self-care as well as formal
      health services. Additional work is needed to explore applicability of the
      Behavioral Model to different types of symptoms, different modalities of self
      care and in countries with different health care systems. Future quantitative
      studies should establish the relative importance of factors influencing the
      actions people take to manage minor symptoms to inform future interventions aimed
      at optimising self-care behaviour.

PMID- 24735227
TI  - Cu-catalyzed direct amidation of aromatic C-H bonds: an access to arylamines.
AB  - A Cu-catalyzed aromatic C-H amidation with phthalimide under oxygen as a terminal
      oxidant without using additional additives has been achieved. This reaction has
      the broad substrate scope and shows moderate to good yields in most cases. This
      method is complementary to the previously reported metal-catalyzed C-H amination
      systems. 

PMID- 24735229
TI  - Satisfaction with sexual life in people living with HIV in Romania, together with
      associated individual and social factors.
AB  - The present study aimed to identify social and individual factors associated with
      satisfaction with sexual life (SSL) in people living with HIV (PLHIV) in contact
      with a community-based organisation in Romania. A standardised questionnaire was
      administered (N = 300) in a community-based research study. Multivariate analysis
      (using a weighted logistic regression restricted to the 291 respondents who
      answered a question about SSL) was used to determine factors associated with SSL.
      Sixty-eight per cent of the participants declared that they were satisfied with
      their sexual life. The following individual factors were associated with SSL:
      being over 36 years old (Odds Ratio [95% CI]: 0.27 [0.13-0.55]), having ceased
      sexual intercourse because of HIV (0.33 [0.14-0.76]), not knowing how infection
      had occurred (0.29 [0.15-0.59]), being officially registered with a level of
      disability lower than "severe" (0.47 [0.23-0.98]) and having a higher self
      efficacy score (1.36 [1.14-1.61]). Living in a couple (7.60 [3.69-15.66]),
      knowing at least one HIV-infected person who had publicly disclosed his/her
      seropositivity (2.23 [1.03-4.84]), and having a higher social exclusion score
      (0.91 [0.82-1]) were social factors associated with SSL. The results suggest that
      HIV service providers must be sensitised to the necessity of systematically
      including the topic of PLHIV SSL in field interventions. Self-empowerment,
      positive examples of public disclosure, promoting the benefits of living in a
      couple, and supporting social integration can all improve the well-being of
      PLHIV, including their SSL. 

PMID- 24735230
TI  - Enhancing Neurobehavioral Gains with the Aid of Games and Exercise (ENGAGE):
      Initial open trial of a novel early intervention fostering the development of
      preschoolers' self-regulation.
AB  - Poor self-regulation during the preschool years predicts a wide array of adverse
      adult outcomes and, as such, is an important treatment target. We assessed the
      efficacy of a novel early intervention aimed at fostering the development of
      preschoolers' self-regulation. Enhancing Neurobehavioral Gains with the Aid of
      Games and Exercise (ENGAGE) involves parents and children playing a wide range of
      games targeting self-regulation on a daily basis over a 5-week period. Twenty
      five New Zealand families, in whom parents identified their children as difficult
      to manage, took part in this study. Parent hyperactivity, aggression, and
      attention problems ratings on the BASC-2 were used to assess improvements in
      behavioral self-regulation, and subtests of the Stanford Binet-5 and NEPSY-2 were
      used to assess improvements in cognitive control. Improvements in parent-rated
      hyperactivity, aggression, and attention problems were maintained throughout the
      12-month follow-up. In addition, improvements were found in two neurocognitive
      areas associated with self-regulation. While more rigorous randomized controlled
      trials are necessary, ENGAGE shows promise as a novel intervention for developing
      self-regulation in at-risk preschoolers. 

PMID- 24735231
TI  - Emotional prosody rarely affects the spatial distribution of visual attention.
AB  - Emotional manipulations have been demonstrated to produce leftward shifts in
      perceptual asymmetries. However, much of this research has used linguistic tasks
      to assess perceptual asymmetry and there are therefore two interpretations of the
      leftward shift. It may reflect a leftward shift in the spatial distribution of
      attention as a consequence of emotional activation of the right hemisphere;
      alternatively it may reflect emotional facilitation of right hemisphere
      linguistic processing. The current study used two non-linguistic attention tasks
      to determine whether emotional prosody influences the spatial distribution of
      visual attention. In a dual-task paradigm participants listened to semantically
      neutral sentences in neutral, happy or sad prosodies while completing a target
      discrimination task (Experiment 1) and a target detection task (Experiments 2 and
      3). There was only one condition in one experiment that induced perceptual
      asymmetries that interacted with emotional prosody, suggesting that task
      irrelevant emotional prosody only rarely directs attention. Instead a more likely
      cause of the leftward perceptual shift for comprehension of emotional speech is
      facilitation of right hemisphere linguistic processing. 

PMID- 24735232
TI  - Age-related decline in lateralised prey capture success in Garnett's bushbaby
      (Otolemur garnettii).
AB  - We examined differences in prey capture success when reaching for moving prey
      with the preferred and non-preferred hand (as determined previously using
      stationary food items) in 12 Garnett's bushbabies (Otolemur garnettii). Hand
      preference was determined by a test of simple reaching for stationary food items.
      We assessed both the frequency of hand use and success rates for each hand in
      capturing live mealworms. We also examined the effect of age on overall prey
      capture success. Subjects were individually presented with live mealworms in a
      cup partially filled with a cornmeal medium. The preferred hand was used
      significantly more often than the non-preferred hand to obtain the moving prey;
      however, no differences were found in the frequency of usage of the left vs the
      right hand. Furthermore, there were no differences in the success rates of the
      left vs the right hand, nor the preferred vs the non-preferred hand. There was a
      significant negative correlation between age and prey capture success. These data
      suggest that age, rather than preferred hand, may be the most relevant factor in
      the bushbabies' prey capture success. 

PMID- 24735233
TI  - The right ear advantage revisited: speech lateralisation in dichotic listening
      using consonant-vowel and vowel-consonant syllables.
AB  - The dichotic listening task is typically administered by presenting a consonant
      vowel (CV) syllable to each ear and asking the participant to report the syllable
      heard most clearly. The results tend to show more reports of the right ear
      syllable than of the left ear syllable, an effect called the right ear advantage
      (REA). The REA is assumed to be due to the crossing over of auditory fibres and
      the processing of language stimuli being lateralised to left temporal areas.
      However, the tendency for most dichotic listening experiments to use only CV
      syllable stimuli limits the extent to which the conclusions can be generalised to
      also apply to other speech phonemes. The current study re-examines the REA in
      dichotic listening by using both CV and vowel-consonant (VC) syllables and
      combinations thereof. Results showed a replication of the REA response pattern
      for both CV and VC syllables, thus indicating that the general assumption of left
      side localisation of processing can be applied for both types of stimuli.
      Further, on trials where a CV is presented in one ear and a VC is presented in
      the other ear, the CV is selected more often than the VC, indicating that these
      phonemes have an acoustic or processing advantage. 

PMID- 24735234
TI  - Four anti-inflammatory drugs induce tolC gene overexpression and repression of
      OmpF synthesis, enhance active efflux and decrease susceptibility to antibiotics
      in Escherichia coli AG100 strain.

PMID- 24735235
TI  - Stereoselective synthesis of quaternary carbons via the dianionic Ireland-Claisen
      rearrangement.
AB  - A dianionic Ireland-Claisen rearrangement of chiral, nonracemic alpha-methyl-beta
      hydroxy allylic esters has been developed that proceeds with high
      diastereoselectivity and provides products containing three contiguous
      stereogenic carbons, including a quaternary center. The potential utility of the
      rearrangement for complex molecule synthesis is also demonstrated. 

PMID- 24735236
TI  - Re-activating modern traditions of justice: mobilising around health in rural
      Tamil Nadu, South India.
AB  - This paper uses empirical material from health activists in Tamil Nadu to show
      that the health discourses that enjoy the greatest continuity and reach in India
      are also those that presume a radical connection between the health of the
      individual body and mobilising for a more just social order. The forging of this
      tradition is traced back to early anti-colonial forms of mobilisation. The
      transmission of this tradition is then ethnographically traced through various
      organisations that relay a characteristic set of orientations of thought and
      action to new generations and groups. The freshness of the synthesis of the
      tradition effected by each activist is emphasised. Arguing along phenomenological
      lines, these capacities to synthesise and renew a tradition are located in the
      capacities of the body. By attending to the unique place of the body in human
      experience, we may be in a better position to also understand the way in which
      health discourses that are embedded within wider experiences of injustice are
      able to circulate with renewed affective force. 

PMID- 24735237
TI  - Cost-effectiveness of family history-based colorectal cancer screening in
      Australia.
AB  - BACKGROUND: With 14.234 diagnoses and over 4047 deaths reported in 2007,
      colorectal cancer (CRC) is the second most common cancer and second most common
      cause of cancer-related mortality in Australia. The direct treatment cost has
      recently been estimated to be around AU$1.2 billion for the year 2011, which
      corresponds to a four-fold increase, compared the cost reported in 2001.
      Excluding CRCs due to known rare genetic disorders, 20% to 25% of all CRCs occur
      in a familial aggregation setting due to genetic variants or shared environmental
      risk factors that are yet to be characterised. A targeted screening strategy
      addressed to this segment of the population is a potentially valuable tool for
      reducing the overall burden of CRC. METHODS: We developed a Markov model to
      assess the cost-effectiveness of three screening strategies offered to people at
      increased risk due to a strong family history of CRC. The model simulated the
      evolution of a cohort of 10,000 individuals from age 50 to 90 years. We compared
      screening with biennial iFOBT, five-yearly colonoscopy and ten-yearly colonoscopy
      versus the current strategy of the Australian National Bowel Cancer Screening
      Programme (i.e. base case). RESULTS: Under the NBCSP scenario, 6,491 persons
      developed CRC with an average screening lifetime cost of AU$3,441 per person. In
      comparison, screening with biennial iFOBT, colonoscopy every ten years, and
      colonoscopy every five years reduced CRC incidence by 27%, 35% and 60%, and
      mortality by 15%, 26% and 46% respectively. All three screening strategies had a
      cost under AU$50,000 per life year gained, which is regarded as the upper limit
      of acceptable cost-effectiveness in the Australian health system. At AU$12,405
      per life year gained and an average lifetime expectancy of 16.084 years, five
      yearly colonoscopy screening was the most cost-effective strategy. CONCLUSION:
      The model demonstrates that intensive CRC screening strategies targeting people
      at increased risk would be cost-effective in the Australian context. Our findings
      provide evidence that substantial health benefits can be generated from risk
      based CRC screening at a relatively modest incremental cost.

PMID- 24735238
TI  - Increased training of general practitioners in Ireland may increase the frequency
      of exercise counselling in patients with chronic illness: a cross-sectional
      study.
AB  - BACKGROUND: Recent systematic reviews have established that brief interventions
      in primary care are effective and economic at promoting physical activity. Lack
      of training has previously been identified as a barrier to lifestyle counselling
      in Ireland. OBJECTIVES: This study evaluates frequency of exercise counselling
      (EC), in patients with six chronic illnesses (type 2 diabetes mellitus, stable
      coronary heart disease, hypertension, depression, obesity, osteoarthritis) and
      healthy adults, by general practitioners (GPs) in the mid-west of Ireland, as
      well as, whether training in EC influences the frequency of EC. METHODS: A
      questionnaire survey of GPs based in the mid-west of Ireland was conducted during
      February and March 2012. The questionnaire was distributed to 39 GPs at two
      continuing medical education meetings and posted to 120 other GPs in the area.
      The questionnaire assessed the frequency of EC, use of written advice and
      frequency of recommending resistance exercise in the above patient groups. It
      also assessed training in EC. RESULTS: 64% of GPs responded (n = 102). Frequency
      of EC varied among the chronic illnesses evaluated. Use of written advice and
      advice on resistance exercise in EC was low. Only 17% of GPs had previous
      training in EC. If available, 94% of GPs would use guidelines to prescribe
      exercise in chronic illness. The association of previous training in EC with
      frequency of EC was variable, with significantly higher counselling rates found
      in T2DM, obesity and healthy adults. CONCLUSION: Improved training of GPs and
      development of guidelines may increase the frequency of EC in Ireland.

PMID- 24735239
TI  - Pathophysiological mechanisms of headache in patients with HIV.
AB  - BACKGROUND: The pathophysiology of human immunodeficiency virus (HIV) is complex.
      The etiology of headache in the HIV population is often multifactorial, and
      attributing causality to specific pathophysiological mechanisms is challenging.
      Headaches can occur any time during the infection and may be primary (as in non
      HIV-infected patients) or secondary (either from HIV directly or due to
      opportunistic disease). DISCUSSION: Direct HIV related headaches are due to the
      underlying viral pathophysiology. For example, acute meningitis can be seen
      during HIV-1 seroconversion. Headaches can occur during symptomatic HIV and also
      after an AIDS-defining illness. Late-stage HIV headache can occur without any
      pleocytosis. A correlation between viral load and neurological symptoms including
      headache has been suggested. There may be similar mechanisms involving migraine,
      tension-type headache, and HIV infection. CONCLUSION: Secondary HIV headaches can
      be related to opportunistic infections, malignancy, medications used to treat
      HIV, and immune restoration inflammatory syndrome.

PMID- 24735240
TI  - A prospective study on association of prostatic calcifications with sexual
      dysfunction in men with chronic prostatitis/chronic pelvic pain syndrome
      (CP/CPPS).
AB  - INTRODUCTION: Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a
      common debilitating condition of unclear etiology. Sexual dysfunction is an
      important component of the clinical phenotype of CP/CPPS. Patients often have
      prostatic calcifications, but a link to sexual dysfunction is unknown. AIM: The
      aim of this study was to evaluate the association of prostatic calcifications
      with sexual dysfunction in this condition. METHODS: A total of 358 males with
      CP/CPPS were consecutively enrolled, and a prospectively maintained database of
      these patients was analyzed. Calcifications were diagnosed using ultrasound
      imaging of the prostate. Symptom severity was measured using the National
      Institutes of Health Chronic Prostatitis Symptom Index (CPSI). Sexual dysfunction
      was evaluated using the validated 15-item International Index of Erectile
      Function (IIEF-15) questionnaire and 5-item Premature Ejaculation Diagnostic Tool
      scales. The variables were compared between patients with prostatic
      calcifications and those without using the Student's t-test, Wilcoxon unpaired
      test, or chi-square test. MAIN OUTCOME MEASURE: Logistic regression models were
      developed to explore a possible association between prostatic calcifications and
      sexual dysfunction. RESULTS: Measurable calcifications in the prostate were found
      in 175 (48.9%) of the 358 patients. Patients with calcifications were more likely
      to have higher white blood cell counts or positive bacteria cultures in their
      prostatic fluid, longer symptoms duration, and lower scores for the total IIEF
      15, IIEF-erectile function, and IIEF-intercourse satisfaction domains (P < 0.001
      for each). However, the scores for CPSI, premature ejaculation, and IIEF-orgasmic
      function, IIEF-sexual desire, and IIEF-overall satisfaction domains were
      identical between men with and without calcifications (P > 0.05 for each).
      Furthermore, logistic regression analyses revealed that intraprostatic
      calcification is significantly associated with self-assessed erectile dysfunction
      (ED) (odds ratio:3.632, 95% confidence interval: 2.405-5.822, P < 0.001).
      CONCLUSION: Our results showed that prostatic calcifications are significantly
      associated with the presence of ED in CP/CPPS males.

PMID- 24735241
TI  - Enhanced performance of organic thin film solar cells using electrodes with
      nanoimprinted light-diffraction and light-diffusion structures.
AB  - An ITO substrate with periodic surface nanostructures was used to induce strong
      diffusion and diffraction of incident light. The nanostructures were fabricated
      using nanoimprint lithography on photoresist followed by coating of the ITO layer
      and organic materials with uniform morphology. The nanostructures embedded into
      the ITO layer were found to increase absorption in poly(3-hexylthiophene):[6,6]
      phenyl-C61-butyric acid methyl ester solar devices. The short-circuit current of
      the nanostructured organic solar cells improved from 7.07 to 10.76 mA/cm2. This
      improvement was due to the increased effective optical path of absorbed light
      resulting from the trapping and scattering by the nanostructures.

PMID- 24735242
TI  - Water oxidation by an electropolymerized catalyst on derivatized mesoporous metal
      oxide electrodes.
AB  - A general electropolymerization/electro-oligomerization strategy is described for
      preparing spatially controlled, multicomponent films and surface assemblies
      having both light harvesting chromophores and water oxidation catalysts on metal
      oxide electrodes for applications in dye-sensitized photoelectrosynthesis cells
      (DSPECs). The chromophore/catalyst ratio is controlled by the number of reductive
      electrochemical cycles. Catalytic rate constants for water oxidation by the
      polymer films are similar to those for the phosphonated molecular catalyst on
      metal oxide electrodes, indicating that the physical properties of the catalysts
      are not significantly altered in the polymer films. Controlled potential
      electrolysis shows sustained water oxidation over multiple hours with no decrease
      in the catalytic current. 

PMID- 24735243
TI  - Oncological outcome and long-term complications in robot-assisted radical surgery
      for early stage cervical cancer: an observational cohort study.
AB  - OBJECTIVE: To report the oncological outcome and long-term complications of
      radical surgery by robot-assisted laparoscopy in early stage cervical cancer.
      DESIGN: Observational cohort study. SETTING: Tertiary referral centre.
      POPULATION: About 100 cervical cancer patients treated consecutively with robot
      assisted radical surgery between 2008 and 2013. METHODS: Two gynaecological
      oncologists specialised in minimally invasive surgery performed all surgeries on
      a three/four-armed robotic system. Procedures consisted of pelvic lymph node
      dissection combined with a radical hysterectomy, radical vaginal trachelectomy or
      parametrectomy. MAIN OUTCOME MEASURES: Recurrence, survival and long-term
      complication rates. RESULTS: 104 robot-assisted laparoscopies were performed in
      100 patients (stage IA1-IIB), with a median follow-up of 29.5 months (range 2.5
      67.1 months). Thirteen cases were diagnosed with a loco-regional (8%), distant
      (4%) or combined (1%) recurrence at a median of 14.4 months (range 2.9-34.8
      months). All mortality (7%) was cervical cancer-related and due to recurrent
      disease. Four recurrences receive palliative care and two are in complete
      remission. The overall 5-year progression-free and disease-specific survival
      rates are 81.4 and 88.7%, respectively. Frequent complications were lymphoedema
      (26%), lower urinary tract symptoms (19%), urinary tract infection (17%) and
      sexual disorders (9%). Five patients had a vaginal cuff dehiscence. No
      complication-related mortality occurred. CONCLUSION: The recurrence, survival and
      long-term complication rates of robot-assisted radical surgery for early stage
      cervical cancer in this cohort are reassuring concerning its continued clinical
      use.

PMID- 24735244
TI  - Antiviral, immunomodulatory, and free radical scavenging activities of a protein
      enriched fraction from the larvae of the housefly, Musca domestica.
AB  - In our previous study, protein-enriched fraction (PEF) that was isolated from the
      larvae of the housefly, Musca domestica L. (Diptera: Muscidae), showed excellent
      hepatoprotective activity as well as the potential for clinical application in
      therapy for liver diseases. In this study, antiviral, immunomodulatory, and free
      radical scavenging activities of PEF were evaluated. The antiviral results
      demonstrated that PEF inhibited the infection of avian influenza virus H9N2 and
      had a virucidal effect against the multicapsid nucleopolyhedrovirus of the
      alfalfa looper, Autographa californica Speyer (Lepidoptera: Noctuidae) in vitro.
      The mortality of silkworm larve in a PEF treatment group decreased significantly
      compared with a negative control. PEF showed excellent scavenging activity for
      1,1-diphenyl-2-picrylhydrazyl and superoxide anion radicals, which were similar
      to those of ascorbic acid. The imunomodulatory results suggested that PEF could
      effectively improve immune function in experimental mice. Our results indicated
      that PEF could possibly be used for the prophylaxis and treatment of diseases
      caused by avian influenza virus infection. In addition, PEF with virucidal
      activity against insect viruses might provide useful for the development of
      antimicrobial breeding technology for economically important insects. As a
      natural product from insects, PEF could be a potential source for the discovery
      of potent antioxidant and immunomodulatory agents.

PMID- 24735245
TI  - Using rifapentine - hen egg lipoprotein conjugate as macrophage-targeted drug
      delivery carrier against intracellular Staphylococcus aureus.
AB  - CONTEXT: Hen egg low-density lipoprotein (heLDL), which is present in large
      quantities in egg yolk, share a high identity with human apolipoprotein B-100
      precursor. OBJECTIVE: This study investigated the use of heLDL as a macrophage
      targeted drug delivery carrier against intracellular Staphylococcus aureus.
      METHODS: Rifapentine (RPT) was incorporated into heLDL (RPT-heLDL).
      Staphylococcus aureus ATCC 29740 and human U937 macrophage were used as
      intracellular infection models. RESULTS AND CONCLUSION: The loading efficiency of
      RPT into the heLDL was 66.10 +/- 2.28 MUg RPT/mg heLDL. Fluorescence microscopy
      and oil red O staining results indicated RPT-heLDL can be taken up by U937
      macrophages. The cell viability (MTT assay) was increased when the concentration
      of heLDL was <150 MUg/mL. Unloaded heLDL (100 MUg/mL) can inhibit the growth of
      intracellular S. aureus compared with the untreated control group after 18 h
      incubation. RPT-heLDL (6.6 MUg/mL RPT, 100 MUg/mL heLDL) eliminated 94% of
      intracellular S. aureus, whereas the corresponding dose of free RPT (6.6 MUg/mL)
      induced an 87% reduction. The in vitro results of the current study indicated
      that heLDL might be used as a suitable drug carrier for targeting human
      macrophages.

PMID- 24735246
TI  - Novel carbopol-based transfersomal gel of 5-fluorouracil for skin cancer
      treatment: in vitro characterization and in vivo study.
AB  - 5-fluorouracil (5-Fu) is an antineoplastic drug, topically used for the treatment
      of actinic keratosis and nonmelanoma skin cancer. It shows poor percutaneous
      permeation through the conventionally applicable creams and thus inefficient for
      the treatment of deep-seated skin cancer. In the present article, transfersomal
      gel containing 5-Fu was investigated for the treatment of skin cancer. Different
      formulation of tranfersomes was prepared using Tween-80 and Span-80 as edge
      activators. The vesicles were characterized for particle size, shape, entrapment
      efficiency, deformability and in vitro skin permeation. Optimized formulation was
      incorporated into 1% carbopol 940 gel and evaluated for efficacy in the treatment
      of skin cancer. 5-Fu-loaded transfersomes (TT-2) has the size of 266.9 +/- 2.04
      nm with 69.2 +/- 0.98% entrapment efficiency and highest deformability index of
      27.8 +/- 1.08. Formulation TT-2 showed maximum skin deposition (81.3%) and
      comparable transdermal flux of 21.46 ug/cm(2) h. The TT-2-loaded gel showed
      better skin penetration and skin deposition of the drug than the marketed
      formulation. Composition of the transfersomal gel has been proved nonirritant to
      the skin. We concluded that the developed 5-Fu-loaded transfersomal gel improves
      the skin absorption of 5-Fu and provide a better treatment for skin cancer.

PMID- 24735247
TI  - Enhanced dissolution and oral bioavailability of valsartan solid dispersions
      prepared by a freeze-drying technique using hydrophilic polymers.
AB  - This study aimed to improve the dissolution rate and oral bioavailability of
      valsartan (VAL), a poorly soluble drug using solid dispersions (SDs). The SDs
      were prepared by a freeze-drying technique with polyethylene glycol 6000
      (PEG6000) and hydroxypropylmethylcellulose (HPMC 100KV) as hydrophilic polymers,
      sodium hydroxide (NaOH) as an alkalizer, and poloxamer 188 as a surfactant
      without using any organic solvents. In vitro dissolution rate and physicochemical
      properties of the SDs were characterized using the USP paddle method,
      differential scanning calorimetry (DSC), X-ray diffractometry (XRD) and Fourier
      transform-infrared (FT-IR) spectroscopy, respectively. In addition, the oral
      bioavailability of SDs in rats was evaluated by using VAL (pure drug) as a
      reference. The dissolution rates of the SDs were significantly improved at pH 1.2
      and pH 6.8 compared to those of the pure drug. The results from DSC, XRD showed
      that VAL was molecularly dispersed in the SDs as an amorphous form. The FT-IR
      results suggested that intermolecular hydrogen bonding had formed between VAL and
      its carriers. The SDs exhibited significantly higher values of AUC 0-24 h and
      Cmax in comparison with the pure drug. In conclusion, hydrophilic polymer-based
      SDs prepared by a freeze-drying technique can be a promising method to enhance
      dissolution rate and oral bioavailability of VAL.

PMID- 24735248
TI  - A comprehensive study of iRGD-modified liposomes with improved chemotherapeutic
      efficacy on B16 melanoma.
AB  - iRGD is a tumor tissue penetrating peptide due to its targeted binding of
      integrin and neuropilin-1 receptors. Whether iRGD carries the liposomes in a
      similar way as it penetrates the cancer drugs or conjugated drugs into tumor
      tissues and cells has not been fully defined. Here, iRGD-modified and doxorubicin
      loaded sterically stabilized liposomes (iRGD-SSL-DOX) and passive liposomes (SSL
      DOX) were prepared. A series of experiments were performed to evaluate the tissue
      penetration, cell penetration, tumor blood vessel damage and anti-tumor effect.
      The results of flow cytometry and confocal microscopy studies showed that iRGD
      SSL-DOX with 5% DSPE-PEG2000-iRGD achieved higher cellular uptake level than that
      of SSL-DOX on B16 melanoma cells. iRGD-SSL-DOX also exhibited stronger cell
      growth inhibition in cytotoxicity experiments. The tumor penetrating effect of
      iRGD was further confirmed by imaging and cellular uptake studies in vivo, in
      which higher distribution of iRGD-modified liposomes in tumor tissue and tumor
      cells was observed. Moreover, iRGD-SSL-DOX displayed improved tumor growth
      inhibition and anti-angiogenesis with less systemic toxicity in an armpit B16
      melanoma model. In conclusion, iRGD reserved its tumor-penetrating properties
      well when modified on the surface of liposomes at optimal density and iRGD-SSL
      DOX would be a promising drug delivery system for active targeting tumor therapy.

PMID- 24735249
TI  - Design of solid lipid nanoparticles for caffeine topical administration.
AB  - CONTEXT: Solid lipid nanoparticles (SLN) are drug carriers possessing numerous
      features useful for topical application. A copious scientific literature outlined
      their ability as potential delivery systems for lipophilic drugs, while the
      entrapment of a hydrophilic drug inside the hydrophobic matrix of SLN is often
      difficult to obtain. OBJECTIVE: To develop SLN intended for loading caffeine (SLN
      CAF) and to evaluate the permeation profile of this substance through the skin
      once released from the lipid nanocarriers. Caffeine is an interesting compound
      showing anticancer and protective effects upon topical administration, although
      its penetration through the skin is compromised by its hydrophilicity. MATERIALS
      AND METHODS: SLN-CAF were formulated by using a modification of the quasi
      emulsion solvent diffusion technique (QESD) and characterized by PCS and DSC
      analyses. In vitro percutaneous absorption studies were effected using excised
      human skin membranes (i.e. Stratum Corneum Epidermis or SCE). RESULTS: SLN-CAF
      were in a nanometric range (182.6 +/- 8.4 nm) and showed an interesting payload
      value (75% +/- 1.1). DSC studies suggest the presence of a well-defined system
      and the successful drug incorporation. Furthermore, SLN-CAF generated a
      significantly faster permeation than a control formulation over 24 h of
      monitoring. DISCUSSION AND CONCLUSIONS: SLN-CAF were characterized by valid
      dimensions and a good encapsulation efficiency, although the active to
      incorporate showed a hydrophilic character. This result confirms the suitability
      of the formulation strategy employed in the present work. Furthermore, the in
      vitro evidence outline the key role of lipid nanoparticles in enhancing caffeine
      permeation through the skin.

PMID- 24735250
TI  - Management and horse-level risk factors for recurrent colic in the UK general
      equine practice population.
AB  - REASONS FOR PERFORMING STUDY: Recurrent colic occurs frequently in the general
      horse population but little evidence exists about what factors place horses at
      greater risk of recurrent colic. OBJECTIVES: To quantify time-varying and non
      time-varying risk factors for recurrent colic among horses attended by first
      opinion veterinary surgeons in northwest England. STUDY DESIGN: Nested case
      control study. METHODS: A nested case-control study was conducted on data from a
      prospective longitudinal cohort study of 127 horses recruited subsequent to an
      episode of medical colic. Data were collected on management and recurrent colic
      episodes at 4-monthly intervals by telephone questionnaires. All recurrent colic
      episodes were selected as cases; controls were unmatched and randomly selected
      from all horse-time at risk. Data relating to the 30 days prior to the date of
      colic or control selection were used to determine exposure status. Multivariable
      logistic regression analyses were used to determine risk factors for recurrent
      colic. RESULTS: In total, 59 cases and 177 controls were included. The final
      model showed that horses that displayed crib-biting/windsucking (odds ratio [OR]
      10.1, 95% confidence interval [CI] 2.5-41.0) or weaving behaviour (OR 3.9, 95% CI
      1.5-10.1) had an increased risk of recurrence of colic. Increasing time at
      pasture reduced the risk of recurrence (OR 0.99, 95% CI 0.99-1.0). A significant
      interaction was found suggesting that the risk associated with crib
      biting/windsucking may be modified by feeding fruit/vegetables; however, further
      research is required before recommendations for feeding practices can be made.
      CONCLUSIONS: This study suggests that sufficient access to pasture may be an
      important means of reducing recurrent colic risk. The behavioural risk factors
      highlight individuals who may be at increased risk of recurrent colic and whose
      colic prevention strategies should be carefully managed.

PMID- 24735251
TI  - The low/high BCS permeability class boundary: physicochemical comparison of
      metoprolol and labetalol.
AB  - Although recognized as overly conservative, metoprolol is currently the common
      low/high BCS permeability class boundary reference compound, while labetalol was
      suggested as a potential alternative. The purpose of this study was to identify
      the various characteristics that the optimal marker should exhibit, and to
      investigate the suitability of labetalol as the permeability class reference
      drug. Labetalol's BCS solubility class was determined, and its physicochemical
      properties and intestinal permeability were thoroughly investigated, both in
      vitro and in vivo in rats, considering the complexity of the whole of the small
      intestine. Labetalol was found to be unequivocally a high-solubility compound. In
      the pH range throughout the small intestine (6.5-7.5), labetalol exhibited pH
      dependent permeability, with higher permeability at higher pH values. While in
      vitro octanol-buffer partitioning (Log D) values of labetalol were significantly
      higher than those of metoprolol, the opposite was evident in the in vitro PAMPA
      permeability assay. The results of the in vivo perfusion studies in rats lay
      between the two contradictory in vitro studies; metoprolol was shown to have
      moderately higher rat intestinal permeability than labetalol. Theoretical
      distribution of the ionic species of the drugs was in corroboration with the
      experimental in vitro and the in vivo data. We propose three characteristics that
      the optimal permeability class reference drug should exhibit: (1) fraction dose
      absorbed in the range of 90%; (2) the optimal marker drug should be absorbed
      largely via passive transcellular permeability, with no/negligible carrier
      mediated active intestinal transport (influx or efflux); and (3) the optimal
      marker drug should preferably be nonionizable. The data presented in this paper
      demonstrate that neither metoprolol nor labetalol can be regarded as optimal
      low/high-permeability class boundary standard. While metoprolol is too
      conservative due to its complete absorption, labetalol has been shown to be a
      substrate for P-gp-mediated efflux transport, and both drugs exhibit significant
      segmental-dependent permeability along the gastrointestinal tract. Nevertheless,
      the use of metoprolol as the marker compound does not carry a risk of
      bioinequivalence: Peff value similar to or higher than metoprolol safely
      indicates high-permeability classification. On the other hand, a more careful
      data analysis is needed if labetalol is used as the reference compound. 

PMID- 24735252
TI  - Diagnostic utility of worry and rumination: a comparison between generalized
      anxiety disorder and major depressive disorder.
AB  - AIM: Although previous reports have addressed worry and rumination as prominent
      cognitive processes in generalized anxiety disorder (GAD) and major depressive
      disorder (MDD) and their distinct correlation with anxious and depressive
      symptoms, the differential association of worry and rumination with the diagnosis
      of GAD and MDD remains unclear. The purpose of this study was to investigate the
      distinct features of worry and rumination in factor structure and their
      predictive validity for the diagnosis of GAD and MDD. METHODS: Four hundred and
      sixty-eight patients with GAD (n = 148) and MDD (n = 320) were enrolled and the
      diagnoses were confirmed with the Structured Clinical Interview for DSM-IV.
      Participants completed the Penn State Worry Questionnaire and Ruminative Response
      Scale and the severity of anxiety and depressive symptoms was assessed via
      clinician ratings. RESULTS: In joint factor analysis using the Penn State Worry
      Questionnaire and Ruminative Response Scale items, worry and rumination emerged
      as distinct factors. In logistic regression analyses, worry contributed to a
      higher probability of the diagnosis of GAD than rumination, as rumination did in
      MDD than worry. CONCLUSION: This is the first comprehensive study investigating
      the diagnostic utility of worry and rumination in a well-defined clinical sample
      of both GAD and MDD. Our results suggest that worry and rumination are distinct
      cognitive processes and play a differential role in the diagnosis of GAD and MDD,
      distinguishing them at the cognitive level.

PMID- 24735253
TI  - Memory T cell proliferative responses and IFN-gamma productivity sustain long
      lasting efficacy of a Cap-based PCV2 vaccine upon PCV2 natural infection and
      associated disease.
AB  - Porcine circovirus type 2 (PCV2) vaccination represents an important measure to
      cope with PCV2 infection; however, data regarding the modulation of the immune
      cell compartment are still limited, especially under field conditions. This study
      is aimed at investigating the features of the cellular immune response in
      conventional piglets induced by vaccination using a capsid (Cap) protein-based
      PCV2 vaccine compared to unvaccinated animals when exposed to PCV2 natural
      infection. Immune reactivity was evaluated by quantifying peripheral cell subsets
      involved in the anti-viral response and characterizing the interferon-gamma (IFN
      gamma) secreting cell (SC) responsiveness both in vivo and upon in vitro whole
      PCV2 recall. The vaccination triggered an early and intense IFN-gamma secreting
      cell response and induced the activation of peripheral lymphocytes. The early
      increase of IFN-gamma SC frequencies resulted in a remarkable and transient
      tendency to increased IFN-gamma productivity in vaccinated pigs. In vaccinated
      animals, soon before the onset of infection occurred 15-16 weeks post
      vaccination, the recalled PCV2-specific immune response was characterized by
      moderate PCV2-specific IFN-gamma secreting cell frequencies and augmented
      productivity together with reactive CD4+CD8+ memory T cells. Conversely, upon
      infection, unvaccinated animals showed very high frequencies of IFN-gamma
      secreting cells and a tendency to lower productivity, which paralleled with
      effector CD4-CD8+ cytotoxic cell responsiveness. The study shows that PCV2
      vaccination induces a long-lasting immunity sustained by memory T cells and IFN
      gamma secreting cells that potentially played a role in preventing the onset of
      infection; the extent and duration of this reactivity can be an important feature
      for evaluating the protective immunity induced by vaccination. 

PMID- 24735254
TI  - Catalytic roles of substrate-binding residues in coenzyme B12-dependent
      ethanolamine ammonia-lyase.
AB  - Ethanolamine ammonia-lyase (EAL) catalyzes the adenosylcobalamin-dependent
      conversion of ethanolamine to acetaldehyde and ammonia. 1-OH of the substrate is
      hydrogen-bonded with Glualpha287, Argalpha160, and Asnalpha193 and 2-NH2 with
      Glualpha287, Glnalpha162, and Aspalpha362. The active site somewhat resembles
      that of diol dehydratase. All five residues were important for the high-affinity
      binding of the substrate and for catalysis. The -COO(-) group at residue alpha287
      was absolutely required for activity and coenzyme Co-C bond cleavage, and there
      was a spatially optimal position for it, suggesting that Glualpha287 contributes
      to Co-C bond homolysis, stabilizes the transition state for the migration of NH2
      from C2 to C1 through partial deprotonation of spectator OH, and functions as a
      base in the elimination of ammonia. A positive charge and/or the hydrogen bond at
      position alpha160 and the hydrogen bonds at positions alpha162 and alpha193 with
      the substrate are important for catalysis and for preventing a radical
      intermediate from undergoing side reactions. Argalpha160 would stabilize the
      trigonal transition state in NH2 migration by electrostatic catalysis and
      hydrogen bonding with spectator OH. Asnalpha193 would contribute to maintaining
      the appropriate position and direction of the guanidinium group of Argalpha160,
      as well. Hydrogen bond acceptors were necessary at position alpha162, but
      hydrogen bond donors were rather harmful. Glnalpha162 might stabilize the
      trigonal transition state by accepting a hydrogen bond from migrating NH3(+). The
      activity was very sensitive to the position of -COO(-) at alpha362. Aspalpha362
      would assist Co-C bond homolysis indirectly and stabilize the trigonal transition
      state by accepting a hydrogen bond from migrating NH3(+) and electrostatic
      interaction.

PMID- 24735255
TI  - Synthesis of substituted styrenes and 3-vinylphenols using ruthenium-catalyzed
      ring-closing enyne metathesis.
AB  - The synthesis of substituted styrenes 3 and 3-vinylphenols 9 was achieved by ring
      closing enyne metathesis (RCEM)/dehydration of 7 and RCEM/tautomerization of 8,
      respectively. Those methods provide selective access to unique aromatic compounds
      and solve the problem of regioisomer formation. 

PMID- 24735256
TI  - High-coordinate gold(I) complexes with dithiocarboxylate ligands.
AB  - Ferrocene dithiocarboxylate has been introduced into the chemistry of gold(I) and
      copper(I). First, a modified synthesis of piperidinium ferrocene
      dithiocarboxylate (1) is reported. Reaction of this reagent with [Au(tht)Cl] in
      the presence of different phosphines resulted in monomeric, dimeric, and
      polymeric structures. Although gold(I) is usually two coordinate, mainly three-
      and four-fold coordinated compounds were obtained by using ferrocene
      dithiocarboxylate as ligands. The isolated compounds are [(FcCSS)Au(PPh3)2] (2)
      (FcCSS = ferrocene dithiocarboxylate), [(FcCSS)Au2(dppm)2] (3) (dppm =
      bis(diphenylphosphino)methane), and [(FcCSS)Au(dppf)]n (4) (dppf =
      bis(diphenylphosphino)ferrocene) [{(FcCSS)Au}2(dppp)] (5) (dppp =
      bis(diphenylphosphino)propane). The FcCSS ligand shows a remarkable flexible
      coordination mode. It coordinates either in a monodentate, a chelating, or in a
      metal bridging mode. In the four gold(I) complexes 2-5 four different
      coordination modes of the FcCSS ligand are seen. Attempts to extend this rich
      coordination chemistry to other coinage metals were only partly successful.
      [(FcCSS)Cu(PPh3)2] (6) was obtained from the reaction of piperidinium ferrocene
      dithiocarboxylate with [(Ph3P)3CuCl]. (57)Fe-Mossbauer spectroscopy was performed
      for compounds 2-4. The spectra show isomer shifts and quadrupole splittings that
      are typical for diamagnetic ferrocenes. 

PMID- 24735257
TI  - Comparison of a new microscopic system for the measurement of residual leucocytes
      in apheresis platelets with flow cytometry and manual counting.
AB  - BACKGROUND AND OBJECTIVES: Since 2001, all blood components in Germany must be
      leucocyte depleted. Recently, a new method for quality control of depletion was
      introduced. Our study aimed at the validation of the method for routine use in
      apheresis platelet concentrates. MATERIALS AND METHODS: We compared the new ADAM
      rWBC device with manual counting in the Nageotte chamber and flow cytometry, two
      standard methods, by measuring residual leucocytes in 40 units of apheresis
      platelet concentrates and in six geometrical dilution series. RESULTS: Cell
      counts of residual leucocytes in the 40 units were below 10(6) cells per
      component with all methods, although mean cell counts were approximately 5 and 6
      times higher in flow cytometry and ADAM-rWBC, respectively, compared to the
      Nageotte chamber. No unit with <10(6) leucocytes was regarded as contaminated.
      The dilution series showed acceptable accuracy, especially in the range around
      the cut-off (approximately 4.5 cells/MUl in components with a volume of 220 ml)
      for regarding a concentrate as contaminated with leucocytes. No sample spiked
      with more than 4.5 cells/MUl was counted as having less. CONCLUSION: In
      comparison with manual counting and flow cytometry, the ADAM-rWBC device
      performed equally. The method is suitable for routine screening of leucocyte
      contamination of apheresis platelets.

PMID- 24735258
TI  - Practices and recommendations in infant feeding and HIV prevention: the child's
      perspective.
AB  - Although the attainment of Millennium Development Goal 4 (MDG 4), reducing under
      five mortality by two-thirds by the year 2015, depends on optimizing breast
      feeding practices in resource-limited settings, there are some conditions in
      which breast-feeding is impossible, contraindicated, or not recommended. The
      overall impact of involuntary nonbreast-feeding on the attainment of MDG 4 has
      not been documented. In industrialized and many middle-income countries
      replacement feeding is affordable, feasible, acceptable, sustainable, and safe
      and complete avoidance of breast-feeding is the norm to prevent postnatal
      transmission of HIV. The situation is very different in many low-income countries
      affected by the HIV epidemic where infants are exposed to HIV and antiretroviral
      (ARV) mediation through breast milk for long periods with risk of acquiring HIV
      infection, development of multidrug resistant HIV and short and long term
      toxicity associated to ARV medications. Despite the obvious needs, there is no
      specific research on how to make replacement feeding safer for infants with no
      access to breast-feeding and for whom replacement feeding is justified. Orphans,
      abandoned and infants of severely ill mothers unable to breast-feed, won't
      benefit from the research done on making breast-feeding safer for HIV exposed
      infants. A child rights perspective illuminates societal obligations to provide
      replacement feeding with infant formula milk to such infants, and to support
      research to make it safer at the same time that breast-feeding is promoted and
      protected for the general population. 

PMID- 24735259
TI  - The impact of a worksite weight management program on obesity: a retrospective
      analysis.
AB  - The objective of this study was to examine the efficacy of a worksite weight
      management program on the reduction of weight and lipid levels in employees and
      their dependents. This retrospective study examined the impact of a one-on-one
      worksite weight management program. Patients with a body mass index (BMI)>30, or
      a BMI>25 and 2 or more risk factors were eligible for inclusion. Laboratory and
      biometric readings at study end were compared to those at baseline. In addition,
      the percentage change of patients reaching recommended guideline levels was
      reported. Of the 310 employees enrolled, 157 completed the program (50.6%) with
      an average weight loss of 5.6%. Improvement was realized for pre-post weight (
      6.0 lbs.; P<=.0001), BMI (-0.9; P<=.0001), blood pressure (systolic: -2.6;
      P<=.0001; diastolic: -1.9; P<=.0001), total cholesterol (-5.9; P=.0485), low
      density lipoprotein cholesterol (LDL; -4.7; P=.0004), and triglycerides (-7.6;
      P=.0060). The proportion moving to within guideline levels increased for the
      following metrics: normal BMI category (2.6%; P=.0060),<30 BMI (10%; P<=.0001),
      systolic and diastolic blood pressure readings (7.7%; P=.0011 and 6.1; P=.0056,
      respectively), total cholesterol (6.5%; P=.0020), LDL (3.9%; P=.0396), and
      triglycerides (4.8; P=.0137). Retention in the worksite program was almost twice
      that seen in some commercial weight loss programs and significant improvements in
      laboratory and biometric readings were achieved. This study suggests that
      employer worksite-based programs may have an important role in improving the
      health of an employee population, which is of particular interest given the high
      prevalence of obesity and its attendant costs.

PMID- 24735260
TI  - RB1 gene in Merkel cell carcinoma: hypermethylation in all tumors and concurrent
      heterozygous deletions in the polyomavirus-negative subgroup.
AB  - Sequestration of the tumor suppressor retinoblastoma protein (RB) by the Merkel
      cell polyomavirus (MCV) is a crucial step in the pathogenesis of Merkel cell
      carcinoma (MCC). RB expression is frequently lost, particularly in MCV-negative
      MCC tumors, through yet unknown mechanisms. We compared the genomic copy number
      changes of 13 MCV-positive and 13 -negative MCC tumors by array comparative
      genomic hybridization. The analysis revealed increased genomic instability,
      amplification of 1p34.3-1p34.2, and losses of 11p in the absence of MCV
      infection. Deletions of the RB1 locus were also detected at high rates in MCV
      negative tumors. None of the tumors with heterozygous RB1 losses expressed RB in
      immunohistochemistry. RB1 promoter hypermethylation was studied with a
      methylation-specific multiplex ligation-dependent probe amplification technique.
      The RB1 promoter was methylated in all tumor specimens at CpG islands located
      close to the ATG start codon, albeit at low levels. The pattern of
      hypermethylation was similar in all MCC samples, despite RB expression, survival
      or MCV status. In conclusion, the frequent heterozygous losses of the RB1 locus
      could partly explain the decreased RB expression in MCV-negative MCC tumors,
      although the effects of RB1 mutations, coinciding promoter hypermethylation and,
      for example, miRNA regulation, cannot be excluded.

PMID- 24735261
TI  - Behavioral and mind/body interventions in headache: unanswered questions and
      future research directions.
AB  - BACKGROUND: Many unanswered questions remain regarding behavioral and mind/body
      interventions in the treatment of primary headache disorders in adults. METHODS:
      We reviewed the literature to ascertain the most pressing unanswered research
      questions regarding behavioral and mind/body interventions for headache. RESULTS:
      We identify the most pressing unanswered research questions in this field,
      describe ideal and practical ways to address these questions, and outline steps
      needed to facilitate these research efforts. We discuss proposed mechanisms of
      action of behavioral and mind/body interventions and outline goals for future
      research in this field. CONCLUSIONS: Although challenges arise from the complex
      nature of the interventions under study, research that adheres to published study
      design and reporting standards and focuses closely on answering key questions is
      most likely to lead to progress in achieving these goals.

PMID- 24735262
TI  - Wiki technology enhanced group project to promote active learning in a
      neuroscience course for first-year medical students: an exploratory study.
AB  - A Wiki group project was integrated into a neuroscience course for first-year
      medical students. The project was developed as a self-directed, collaborative
      learning task to help medical students review course content and make clinically
      important connections. The goals of the project were to enhance students'
      understanding of key concepts in neuroscience, promote active learning, and
      reinforce their information literacy skills. The objective of the exploratory
      study was to provide a formative evaluation of the Wiki group project and to
      examine how Wiki technology was utilized to enhance active and collaborative
      learning of first-year medical students in the course and to reinforce
      information literacy skills.

PMID- 24735263
TI  - Establishing a new clinical informationist role in an academic health sciences
      center.
AB  - The concept of clinical informationists is not new, but has recently been gaining
      more widespread acceptance across the United States. This article describes the
      lessons and challenges learned from starting a new clinical informationist
      service targeted to internal medicine residents in a large academic medical
      center. Lessons included the need for becoming immersed in evidence-based
      practice fundamentals; becoming comfortable with the pace, realities, and topics
      encountered during clinical rounds; and needing organizational commitment to both
      the evidence-based practice paradigm and clinical informationist role. Challenges
      included adapting to organizational culture, resident burnout, and perceptions of
      information overload. 

PMID- 24735264
TI  - Book discussion course: timely topics for medical students.
AB  - Several library faculty members at the Louisiana State University Health
      Shreveport Health Sciences Library offered a book discussion course as an
      elective for first-year medical students. This article provides details on how
      the librarians developed, taught, and evaluated this elective. The librarians
      took a team-teaching approach, required the students to read two books, and
      outlined the criteria for participation. At the end of the course, the students
      completed an evaluation, commenting on positive and negative aspects of the
      course. The elective proved to be successful, and the librarians look forward to
      offering the course again in the spring of 2014. 

PMID- 24735265
TI  - Leveraging technology and staffing in developing a new liaison program.
AB  - With nearly all library resources and services delivered digitally, librarians
      working for the New York University Health Sciences Library struggled with
      maintaining awareness of changing user needs, understanding barriers faced in
      using library resources and services, and determining knowledge management
      challenges across the organization. A liaison program was created to provide
      opportunities for librarians to meaningfully engage with users. The program was
      directed toward a subset of high-priority user groups to provide focused
      engagement with these users. Responsibility for providing routine reference
      service was reduced for liaison librarians to provide maximum time to engage with
      their assigned user communities. 

PMID- 24735266
TI  - Development of a Web-based repository for sharing biomedical terminology from
      systematic review searches: a case study.
AB  - Requests for comprehensive searches, such as searches to support systematic
      reviews, seem to be evolving into routine practice in the health sciences library
      environment. Collecting terminology for these searches is often a time-consuming
      process. This case study reports on the development of a searchable Web-based
      repository, MedTerm Search Assist, as a means for librarians to share biomedical
      terminology from systematic review searches.

PMID- 24735267
TI  - Library support of mobile resources during clinical clerkships.
AB  - In response to frequent use of mobile devices among medical students, Dana
      Medical Library at the University of Vermont provided mobile resource support to
      medical students preparing for clerkships. The librarians offered group
      instruction, individual assistance, and an online subject guide. These activities
      were assessed through evaluations, web statistics, and a survey. Survey questions
      gathered data on access to mobile devices, use of library-licensed mobile
      resources, and benefits and barriers to use in the clinical setting. The majority
      of survey respondents believed access to mobile resources improved their
      clerkship experience and contributed to comparable educational experiences across
      clerkship sites. Researchers found that library support affected student
      perception of the value of mobile resources in the clerkship experience. 

PMID- 24735268
TI  - FastStats: a public health statistics database.
AB  - FastStats is a site that provides quick and easy access to public health
      statistics. The freely available website is maintained by the Centers for Disease
      Control and Prevention's National Center for Health Statistics. Users can browse
      alphabetically by topic and state/territory or search across the National Center
      for Health Statistics site. A description of the browsing capabilities and sample
      searches are presented. 

PMID- 24735269
TI  - Taking advantage of Google's Web-based applications and services.
AB  - Google is a company that is constantly expanding and growing its services and
      products. While most librarians possess a "love/hate" relationship with Google,
      there are a number of reasons you should consider exploring some of the tools
      Google has created and made freely available. Applications and services such as
      Google Docs, Slides, and Google+ are functional and dynamic without the cost of
      comparable products. This column will address some of the issues users should be
      aware of before signing up to use Google's tools, and a description of some of
      Google's Web applications and services, plus how they can be useful to librarians
      in health care.

PMID- 24735270
TI  - Books, children, dogs, artists: library programs for the entire family.
AB  - The promotion of library resources and services is a continuous process for all
      libraries, especially hospital family resource center libraries. Like public
      libraries, a family resource center can utilize programs as a pathway for
      connecting with and developing awareness of library resources and services
      available to patient families. This column describes the programs currently
      offered for All Children's Hospital Johns Hopkins Medicine patient families,
      marketing initiatives to promote these programs, and utilization of grant funding
      to supplement a program. 

PMID- 24735271
TI  - Helping improve dissemination of research: Toastmasters is a novel mechanism.
AB  - Competencies for health professionals and students often include the ability to
      transfer knowledge to different audiences in a variety of ways. Consultation,
      presentation, teaching, multimedia, and posters are some examples. A recent
      question on a national listserv about writing, editing, and proofreading services
      in health sciences libraries prompted this column about a potentially novel way
      of helping students and faculty in health disciplines to improve their abilities
      to communicate professionally. In addition to the poster design and review
      services that one library offers, it is also the host of two Toastmasters
      International clubs that provide participants a nonthreatening, real-world
      environment to improve the content, structure, methods, and delivery of their
      written and spoken messages. A librarian on staff is a member of and serves as
      liaison to the two clubs. 

PMID- 24735276
TI  - Impact of urinary incontinence on sexual functioning in community-dwelling older
      women.
AB  - INTRODUCTION: Knowledge on the sexual health of patients with urinary
      incontinence in primary care is scarce; therefore, the impact of urinary
      incontinence on sexual functioning was examined in community-dwelling older
      women. AIM: The aim of this study was to provide primary health care
      professionals with more information on the sexual health of older women with
      urinary incontinence, which can be used to discuss this sensitive topic during a
      consultation. METHOD: A cross-sectional survey among the 350 women aged >=55
      years participating in a primary care trial on urinary incontinence was
      conducted. MAIN OUTCOME MEASURES: Among patients with a partner, sexual problems
      of the sexually active patients were described as well as reasons for not being
      sexually active. A multivariate logistic regression model was performed to
      identify factors that are predictors of sexual activity, and odds ratios (ORs)
      and 95% confidence intervals (CIs) were estimated. RESULTS: Of all participants
      with a partner, 68% (95% CI: 61-74) were sexually active. Of these, 25% (95% CI:
      17-35) felt restricted in (or avoided) sexual activity because of their urinary
      incontinence. Urine leakage during sexual activity was present in 26% (95% CI: 19
      34). The most frequent reason for not being sexually active was a physical
      problem of their partner (28%, 95% CI: 18-40); only 5% (95%-CI: 2-13) reported
      that urinary incontinence was a reason for not having sex. Increasing age was the
      only independent (negative) predictor of sexual activity (OR: 0.95, 95%-CI: 0.90
      1.00). CONCLUSIONS: Most of these older women with urinary incontinence were
      sexually active, if they had a partner. The main reason for not being sexually
      active was a partner-related problem. Although for only 5% was urinary
      incontinence the main reason for not having sex, about 25% of the sexually active
      women reported a negative influence of urine loss on their sex life. This implies
      that assessing sexual function is relevant in older women with urinary
      incontinence.

PMID- 24735277
TI  - Anodes for sodium ion batteries based on tin-germanium-antimony alloys.
AB  - Here we provide the first report on several compositions of ternary Sn-Ge-Sb thin
      film alloys for application as sodium ion battery (aka NIB, NaB or SIB) anodes,
      employing Sn50Ge50, Sb50Ge50, and pure Sn, Ge, Sb as baselines. Sn33Ge33Sb33,
      Sn50Ge25Sb25, Sn60Ge20Sb20, and Sn50Ge50 all demonstrate promising
      electrochemical behavior, with Sn50Ge25Sb25 being the best overall. This alloy
      has an initial reversible specific capacity of 833 mAhg(-1) (at 85 mAg(-1)) and
      662 mAhg(-1) after 50 charge-discharge cycles. Sn50Ge25Sb25 also shows excellent
      rate capability, displaying a stable capacity of 381 mAhg(-1) at a current
      density of 8500 mAg(-1) (~10C). A survey of published literature indicates that
      833 mAhg(-1) is among the highest reversible capacities reported for a Sn-based
      NIB anode, while 381 mAhg(-1) represents the optimum fast charge value. HRTEM
      shows that Sn50Ge25Sb25 is a composite of 10-15 nm Sn and Sn-alloyed Ge
      nanocrystallites that are densely dispersed within an amorphous matrix. Comparing
      the microstructures of alloys where the capacity significantly exceeds the rule
      of mixtures prediction to those where it does not leads us to hypothesize that
      this new phenomenon originates from the Ge(Sn) that is able to sodiate beyond the
      1:1 Na:Ge ratio reported for the pure element. Combined TOF-SIMS, EELS TEM, and
      FIB analysis demonstrates substantial Na segregation within the film near the
      current collector interface that is present as early as the second discharge,
      followed by cycling-induced delamination from the current collector. 

PMID- 24735279
TI  - Young women's education and behavioural risk trajectories: clarifying their
      association with unintended-pregnancy resolution.
AB  - In the USA, most pregnancies occurring to teenage women are unplanned, making
      both the decisions regarding their resolution and the consequences of those
      decisions important topics of inquiry. Substantial debate surrounds the potential
      consequences for young women of either carrying an unintended pregnancy to term
      or voluntarily terminating it. The present study utilises data from The US
      National Longitudinal Study of Adolescent Health prospectively to examine the
      predictors of pregnancy resolution decisions in terms of young women's
      educational goals and their engagement in risk behaviours. Additionally, the long
      term consequences of these decisions for education and risk-taking behaviours are
      identified. Results indicate that young women with strong educational goals have
      a greater likelihood of terminating an unintended pregnancy than those with low
      aspirations, and that pregnancy termination predicts higher educational
      attainment compared to motherhood. Risk behaviours did not predict pregnancy
      resolution decisions, but young women who became mothers reported lower rates of
      subsequent substance use and fewer sexual partners post-pregnancy than those who
      terminated the pregnancy or who had never been pregnant. Motherhood appears to be
      a catalyst for lifestyle change among young women, limiting substance use and
      sexual partnering, in contrast to abortion, which appears to allow adolescents to
      continue risk-taking trajectories. 

PMID- 24735278
TI  - Type 1 diabetes - impact on children and parents at diagnosis and 1 year
      subsequent to the child's diagnosis.
AB  - BACKGROUND AND AIM: When a child is diagnosed with type 1 diabetes, it is a
      complex and challenging situation for the whole family. The management of the
      disease places substantial demands on the family and they need to change their
      daily life. The short- and long-term impact on the family has rarely been
      described; therefore, the aim of this study was to describe and compare the
      disease impact on parents and children in terms of health-related quality of life
      (HRQOL) at diagnosis and 1 year subsequent to the child's diagnosis with type 1
      diabetes. A further aim was to describe and compare the parents' satisfaction
      with the care received. METHOD: Sixty-nine children and their parents were
      included. Parents independently filled in the PedsQL(TM) Family Impact Module and
      the PedsQL(TM) Health Care Satisfaction Generic Module. The PedsQL(TM) 3.0
      Diabetes Module was filled in by parents and children over the age of 5. RESULTS:
      Mothers reported a lower HRQOL than fathers both at the time of diagnosis (p =
      0.003) and 1 year later (p = 0.041). For diabetes-specific HRQOL, children aged 5
      7 years and their parents reported more worry than children and parents in older
      age groups (p = 0.037). Children aged 8-12 and 13-18 years reported a higher
      treatment adherence than mothers (p = 0.011 and p = 0.039, respectively); no
      differences were found between children and fathers. Both parents expressed
      overall satisfaction with the child's health care. CONCLUSION: The family is
      affected during the first year after their child is diagnosed with type 1
      diabetes. Both parents and the youngest children estimated a high degree of
      worry. The diabetes team needs to be aware of this and to take it into
      consideration.

PMID- 24735280
TI  - Geographic distribution of habitat, development, and population growth rates of
      the Asian citrus psyllid, Diaphorina citri, in Mexico.
AB  - The Asian citrus psyllid, Diaphorina citri Kuwayama (Hemiptera: Psyllidae), is an
      introduced pest in Mexico and a vector of huanglongbing, a lethal citrus disease.
      Estimations of the habitat distribution and population growth rates of D. citri
      are required to establish regional and areawide management strategies and can be
      used as a pest risk analysis tools. In this study, the habitat distribution of D.
      citri in Mexico was computed with MaxEnt, an inductive, machine-learning program
      that uses bioclimatic layers and point location data. Geographic distributions of
      development and population growth rates were determined by fitting a temperature
      dependent, nonlinear model and projecting the rates over the target area, using
      the annual mean temperature as the predictor variable. The results showed that
      the most suitable regions for habitat of D. citri comprise the Gulf of Mexico
      states, Yucatan Peninsula, and areas scattered throughout the Pacific coastal
      states. Less suitable areas occurred in northern and central states. The most
      important predictor variables were related to temperature. Development and growth
      rates had a distribution wider than habitat, reaching some of the northern states
      of Mexico. Habitat, development, and population growth rates were correlated to
      each other and with the citrus producing area. These relationships indicated that
      citrus producing states are within the most suitable regions for the occurrence,
      development, and population growth of D. citri, therefore increasing the risk of
      huanglongbing dispersion.

PMID- 24735281
TI  - Communication: Determining the structure of the N2Ar van der Waals complex with
      laser-based channel-selected Coulomb explosion.
AB  - We experimentally reconstructed the structure of the N2Ar van der Waals complex
      with the technique of laser-based channel-selected Coulomb explosion imaging. The
      internuclear distance between the N2 center of mass and the Ar atom, i.e., the
      length of the van der Waals bond, was determined to be 3.88 A from the two-body
      explosion channels. The angle between the van der Waals bond and the N2 principal
      axis was determined to be 90 degrees  from the three-body explosion channels. The
      reconstructed structure was contrasted with our high level ab initio
      calculations. The agreement demonstrated the potential application of laser-based
      Coulomb explosion in imaging transient molecular structure, particularly for
      floppy van der Waals complexes, whose structures remain difficult to be
      determined by conventional spectroscopic methods.

PMID- 24735282
TI  - Unrestricted density functional theory based on the fragment molecular orbital
      method for the ground and excited state calculations of large systems.
AB  - We extended the fragment molecular orbital (FMO) method interfaced with density
      functional theory (DFT) into spin unrestricted formalism (UDFT) and developed
      energy gradients for the ground state and single point excited state energies
      based on time-dependent DFT. The accuracy of FMO is evaluated in comparison to
      the full calculations without fragmentation. Electronic excitations in solvated
      organic radicals and in the blue copper protein, plastocyanin (PDB code: 1BXV),
      are reported. The contributions of solvent molecules to the electronic
      excitations are analyzed in terms of the fragment polarization and quantum
      effects such as interfragment charge transfer. 

PMID- 24735283
TI  - Theory of ultrafast photoinduced electron transfer from a bulk semiconductor to a
      quantum dot.
AB  - This paper describes analytical and numerical results from a model Hamiltonian
      method applied to electron transfer (ET) from a quasicontinuum (QC) of states to
      a set of discrete states, with and without a mediating bridge. Analysis of the
      factors that determine ET dynamics yields guidelines for achieving high-yield
      electron transfer in these systems, desired for instance for applications in
      heterogeneous catalysis. These include the choice of parameters of the laser
      pulse that excites the initial state into a continuum electronic wavepacket and
      the design of the coupling between the bridge molecule and the donor and
      acceptor. The vibrational mode on a bridging molecule between donor and acceptor
      has an influence on the yield of electron transfer via Franck-Condon factors,
      even in cases where excited vibrational states are only transiently populated.
      Laser-induced coherence of the initial state as well as energetic overlap is
      crucial in determining the ET yield from a QC to a discrete state, whereas the ET
      time is influenced by competing factors from the coupling strength and the
      coherence properties of the electronic wavepacket. 

PMID- 24735284
TI  - Derivation of spin-orbit couplings in collinear linear-response TDDFT: a rigorous
      formulation.
AB  - Using an approach based upon a set of auxiliary many-electron wavefunctions we
      present a rigorous derivation of spin-orbit coupling (SOC) within the framework
      of linear-response time-dependent density functional theory (LR-TDDFT). Our
      method is based on a perturbative correction of the non-relativistic collinear
      TDDFT equations using a Breit-Pauli spin-orbit Hamiltonian. The derivation, which
      is performed within both the Casida and Sternheimer formulations of LR-TDDFT, is
      valid for any basis set. The requirement of spin noncollinearity for the
      treatment of spin-flip transitions is also discussed and a possible alternative
      solution for the description of these transitions in the collinear case is also
      proposed. Our results are validated by computing the SOC matrix elements between
      singlet and triplet states of two molecules, formaldehyde and acetone. In both
      cases, we find excellent agreement with benchmark calculations performed with a
      high level correlated wavefunction method. 

PMID- 24735285
TI  - FOHI-D: an iterative Hirshfeld procedure including atomic dipoles.
AB  - In this work, a new partitioning method based on the FOHI method (fractional
      occupation Hirshfeld-I method) will be discussed. The new FOHI-D method uses an
      iterative scheme in which both the atomic charge and atomic dipole are calculated
      self-consistently. In order to induce the dipole moment on the atom, an electric
      field is applied during the atomic SCF calculations. Based on two sets of
      molecules, the atomic charge and intrinsic atomic dipole moment of hydrogen and
      chlorine atoms are compared using the iterative Hirshfeld (HI) method, the
      iterative Stockholder atoms (ISA) method, the FOHI method, and the FOHI-D method.
      The results obtained are further analyzed as a function of the group
      electronegativity of Boyd et al. [J. Am. Chem. Soc. 110, 4182 (1988); Boyd et
      al., J. Am. Chem. Soc. 114, 1652 (1992)] and De Proft et al. [J. Phys. Chem. 97,
      1826 (1993)]. The molecular electrostatic potential (ESP) based on the HI, ISA,
      FOHI, and FOHI-D charges is compared with the ab initio ESP. Finally, the effect
      of adding HI, ISA, FOHI, and FOHI-D atomic dipoles to the multipole expansion as
      a function of the precision of the ESP is analyzed. 

PMID- 24735286
TI  - Multidimensional spectroscopy with a single broadband phase-shaped laser pulse.
AB  - We calculate the frequency-dispersed nonlinear transmission signal of a phase
      shaped visible pulse to fourth order in the field. Two phase profiles, a phase
      step and phase-pulse, are considered. Two dimensional signals obtained by varying
      the detected frequency and phase parameters are presented for a three electronic
      band model system. We demonstrate how two-photon and stimulated Raman resonances
      can be manipulated by the phase profile and sign, and selected quantum pathways
      can be suppressed. 

PMID- 24735287
TI  - Nonequilibrium fluctuation-dissipation relations for one- and two-particle
      correlation functions in steady-state quantum transport.
AB  - We study the non-equilibrium (NE) fluctuation-dissipation (FD) relations in the
      context of quantum thermoelectric transport through a two-terminal nanodevice in
      the steady-state. The FD relations for the one- and two-particle correlation
      functions are derived for a model of the central region consisting of a single
      electron level. Explicit expressions for the FD relations of the Green's
      functions (one-particle correlations) are provided. The FD relations for the
      current-current and charge-charge (two-particle) correlations are calculated
      numerically. We use self-consistent NE Green's functions calculations to treat
      the system in the absence and in the presence of interaction (electron-phonon) in
      the central region. We show that, for this model, there is no single universal FD
      theorem for the NE steady state. There are different FD relations for each
      different class of problems. We find that the FD relations for the one-particle
      correlation function are strongly dependent on both the NE conditions and the
      interactions, while the FD relations of the current-current correlation function
      are much less dependent on the interaction. The latter property suggests
      interesting applications for single-molecule and other nanoscale transport
      experiments. 

PMID- 24735288
TI  - mBEEF: an accurate semi-local Bayesian error estimation density functional.
AB  - We present a general-purpose meta-generalized gradient approximation (MGGA)
      exchange-correlation functional generated within the Bayesian error estimation
      functional framework [J. Wellendorff, K. T. Lundgaard, A. Mogelhoj, V. Petzold,
      D. D. Landis, J. K. Norskov, T. Bligaard, and K. W. Jacobsen, Phys. Rev. B 85,
      235149 (2012)]. The functional is designed to give reasonably accurate density
      functional theory (DFT) predictions of a broad range of properties in materials
      physics and chemistry, while exhibiting a high degree of transferability.
      Particularly, it improves upon solid cohesive energies and lattice constants over
      the BEEF-vdW functional without compromising high performance on adsorption and
      reaction energies. We thus expect it to be particularly well-suited for studies
      in surface science and catalysis. An ensemble of functionals for error estimation
      in DFT is an intrinsic feature of exchange-correlation models designed this way,
      and we show how the Bayesian ensemble may provide a systematic analysis of the
      reliability of DFT based simulations. 

PMID- 24735289
TI  - Polarizability effects on the structure and dynamics of ionic liquids.
AB  - Polarization effects on the structure and dynamics of ionic liquids are
      investigated using molecular dynamics simulations. Four different ionic liquids
      were simulated, formed by the anions Cl(-) and PF6(-), treated as single fixed
      charge sites, and the 1-n-alkyl-3-methylimidazolium cations (1-ethyl and 1-butyl
      ), which are polarizable. The partial charge fluctuation of the cations is
      provided by the electronegativity equalization model (EEM) and a complete
      parameter set for the cations electronegativity (chi) and hardness (J) is
      presented. Results obtained from a non-polarizable model for the cations are also
      reported for comparison. Relative to the fixed charged model, the equilibrium
      structure of the first solvation shell around the imidazolium cations shows that
      inclusion of EEM polarization forces brings cations closer to each other and that
      anions are preferentially distributed above and below the plane of the
      imidazolium ring. The polarizable model yields faster translational and
      reorientational dynamics than the fixed charges model in the rotational-diffusion
      regime. In this sense, the polarizable model dynamics is in better agreement with
      the experimental data.

PMID- 24735290
TI  - Theory and efficient computation of differential vibrational spectra.
AB  - We developed a general computational scheme for differential spectra on the basis
      of time correlation function and perturbation theory. The scheme provides a quite
      efficient route to evaluate small differential spectra by molecular dynamics
      simulation instead of the straightforward subtraction of two spectra.
      Applications of this scheme have demonstrated that the proposed route is accurate
      and far more efficient in several orders of magnitude. The present method enables
      us to analyze a variety of experimental differential spectra using molecular
      dynamics simulation. 

PMID- 24735291
TI  - Investigation of giant magnetoconductance in organic devices based on hopping
      mechanism.
AB  - We suggest a spin-dependent hopping mechanism which includes the effect of the
      external magnetic field as well as hyperfine interaction (HFI) to explain the
      observed giant magnetoconductance (MC) in non-magnetic organic devices. Based on
      the extended Marcus theory, we calculate the MC by using the master equation. It
      is found that a MC value as large as 91% is obtained under a low driving voltage.
      For suitable parameters, the theoretical results are in good agreement with the
      experimental data. Influences of the carrier density, HFI, and the carrier
      localization on the MC value are investigated. Especially, it is found that a low
      dimensional structure of the organic materials is favorable to get a large MC
      value. 

PMID- 24735292
TI  - Second-order perturbative corrections to the restricted active space
      configuration interaction with the hole and particle approach.
AB  - Second-order corrections to the restricted active space configuration interaction
      (RASCI) with the hole and particle truncation of the excitation operator are
      developed. Theoretically, the computational cost of the implemented perturbative
      approach, abbreviated as RASCI(2), grows like its single reference counterpart in
      MP2. Two different forms of RASCI(2) have been explored, that is the generalized
      Davidson-Kapuy and the Epstein-Nesbet partitions of the Hamiltonian. The
      preliminary results indicate that the use of energy level shift of a few tenths
      of a Hartree might systematically improve the accuracy of the RASCI(2) energies.
      The method has been tested in the computation of the ground state energy profiles
      along the dissociation of the hydrogen fluoride and N2 molecules, the computation
      of correlation energy in the G2/97 molecular test set, and in the computation of
      excitation energies to low-lying states in small organic molecules. 

PMID- 24735293
TI  - Size dependent transition to solid hydrogen and argon clusters probed via
      spectroscopy of PTCDA embedded in helium nanodroplets.
AB  - Complexes made of either Ar(N) or (H2)N clusters (N = 1-170) and a single PTCDA
      molecule (3,4,9,10-perylene-tetracarboxylic-dianhydride) are assembled inside
      helium droplets and spectroscopically studied via laser-induced fluorescence
      spectroscopy. The frequency shift and line-broadening are analyzed as a function
      of N and of the pick-up order of the PTCDA and cluster material in order to track
      liquid or solid properties of the clusters. For argon, the solid phase is
      observed for N > 10 above which the pick-up order dramatically influences the
      localization of the chromophore with respect to the Ar cluster. If the droplets
      are doped first with Ar, the chromophore remains on the surface of a solid
      cluster whereas for the reversed pick-up order the molecule is surrounded by an
      argon shell. At N < 10 wetting and the formation of the first solvation shell are
      observed. For para-hydrogen, a transition to the solid is observed at N ~ 20-25,
      confirming previous theoretical predictions on the existence of a liquid-like
      phase at such small sizes, even below the bulk hydrogen freezing temperature.

PMID- 24735294
TI  - Global optimization of cholic acid aggregates.
AB  - In spite of recent investigations into the potential pharmaceutical importance of
      bile acids as drug carriers, the structure of bile acid aggregates is largely
      unknown. Here, we used global optimization techniques to find the lowest energy
      configurations for clusters composed between 2 and 10 cholate molecules, and
      evaluated the relative stabilities of the global minima. We found that the
      energetically most preferred geometries for small aggregates are in fact reverse
      micellar arrangements, and the classical micellar behaviour (efficient burial of
      hydrophobic parts) is achieved only in systems containing more than five cholate
      units. Hydrogen bonding plays a very important part in keeping together the
      monomers, and among the size range considered, the most stable structure was
      found to be the decamer, having 17 hydrogen bonds. Molecular dynamics simulations
      showed that the decamer has the lowest dissociation propensity among the studied
      aggregation numbers. 

PMID- 24735295
TI  - Theoretical prediction of nuclear magnetic shieldings and indirect spin-spin
      coupling constants in 1,1-, cis-, and trans-1,2-difluoroethylenes.
AB  - A theoretical prediction of nuclear magnetic shieldings and indirect spin-spin
      coupling constants in 1,1-, cis- and trans-1,2-difluoroethylenes is reported. The
      results obtained using density functional theory (DFT) combined with large basis
      sets and gauge-independent atomic orbital calculations were critically compared
      with experiment and conventional, higher level correlated electronic structure
      methods. Accurate structural, vibrational, and NMR parameters of
      difluoroethylenes were obtained using several density functionals combined with
      dedicated basis sets. B3LYP/6-311++G(3df,2pd) optimized structures of
      difluoroethylenes closely reproduced experimental geometries and earlier reported
      benchmark coupled cluster results, while BLYP/6-311++G(3df,2pd) produced accurate
      harmonic vibrational frequencies. The most accurate vibrations were obtained
      using B3LYP/6-311++G(3df,2pd) with correction for anharmonicity. Becke half and
      half (BHandH) density functional predicted more accurate (19)F isotropic
      shieldings and van Voorhis and Scuseria's tau-dependent gradient-corrected
      correlation functional yielded better carbon shieldings than B3LYP. A
      surprisingly good performance of Hartree-Fock (HF) method in predicting nuclear
      shieldings in these molecules was observed. Inclusion of zero-point vibrational
      correction markedly improved agreement with experiment for nuclear shieldings
      calculated by HF, MP2, CCSD, and CCSD(T) methods but worsened the DFT results.
      The threefold improvement in accuracy when predicting (2)J(FF) in 1,1
      difluoroethylene for BHandH density functional compared to B3LYP was observed
      (the deviations from experiment were -46 vs. -115 Hz). 

PMID- 24735296
TI  - Non-covalent interactions of nitrous oxide with aromatic compounds: spectroscopic
      and computational evidence for the formation of 1:1 complexes.
AB  - We present the first study of intermolecular interactions between nitrous oxide
      (N2O) and three representative aromatic compounds (ACs): phenol, cresol, and
      toluene. The infrared spectroscopic experiments were performed in a Ne matrix and
      were supported by high-level quantum chemical calculations. Comparisons of the
      calculated and experimental vibrational spectra provide direct identification and
      characterization of the 1:1 N2O-AC complexes. Our results show that N2O is
      capable of forming non-covalently bonded complexes with ACs. Complex formation is
      dominated by dispersion forces, and the interaction energies are relatively low
      (about -3 kcal mol(-1)); however, the complexes are clearly detected by frequency
      shifts of the characteristic bands. These results suggest that N2O can be bound
      to the amino-acid residues tyrosine or phenylalanine in the form of pi complexes.

PMID- 24735297
TI  - Solvation of molecules in superfluid helium enhances the "interaction induced
      localization" effect.
AB  - Atomic nuclei become delocalized at low temperatures as a result of quantum
      effects, whereas they are point-like in the high temperature (classical) limit.
      For non-interacting nuclei, the delocalization upon lowering the temperature is
      quantitatively described in terms of the thermal de Broglie wavelength of free
      particles. Clearly, light non-interacting nuclei--the proton being a prominent
      one--are much more delocalized at low temperatures compared to heavy nuclei, such
      as non-interacting oxygen having water in mind. However, strong interactions due
      to chemical bonding in conjunction with ultra-low temperatures characteristic to
      superfluid helium nanodroplets change this common picture substantially for
      nuclei in molecules or clusters. It turns out that protons shared in hydrogen
      bonds undergo an extreme "interaction induced localization" at temperatures on
      the order of 1 K, which compresses the protonic spatial distributions to the size
      of the much heavier donor or acceptor atoms, such as O or Cl nuclei,
      corresponding to about 0.1% of the volume occupied by a non-interacting proton at
      the same temperature. Moreover, applying our recently developed hybrid ab initio
      path integral molecular dynamics/bosonic path integral Monte Carlo quantum
      simulation technique to a HCl/water cluster, HCl(H2O)4, we find that helium
      solvation has a significant additional localizing effect of up to about 30% in
      volume. In particular, the solvent-induced excess localization is the stronger
      the lesser the given nucleus is already localized in the gas phase reference
      situation.

PMID- 24735298
TI  - Magnetic properties and hyperfine interactions in Cr8, Cr7Cd, and Cr7Ni molecular
      rings from 19F-NMR.
AB  - A detailed experimental investigation of the (19)F nuclear magnetic resonance is
      made on single crystals of the homometallic Cr8 antiferromagnetic molecular ring
      and heterometallic Cr7Cd and Cr7Ni rings in the low temperature ground state.
      Since the F(-) ion is located midway between neighboring magnetic metal ions in
      the ring, the (19)F-NMR spectra yield information about the local electronic spin
      density and (19)F hyperfine interactions. In Cr8, where the ground state is a
      singlet with total spin S(T) = 0, the (19)F-NMR spectra at 1.7 K and low external
      magnetic field display a single narrow line, while when the magnetic field is
      increased towards the first level crossing field, satellite lines appear in the
      (19)F-NMR spectrum, indicating a progressive increase in the Boltzmann population
      of the first excited state S(T) = 1. In the heterometallic rings, Cr7Cd and
      Cr7Ni, whose ground state is magnetic with S(T) = 3/2 and S(T) = 1/2,
      respectively, the (19)F-NMR spectrum has a complicated structure which depends on
      the strength and orientation of the magnetic field, due to both isotropic and
      anisotropic transferred hyperfine interactions and classical dipolar
      interactions. From the (19)F-NMR spectra in single crystals we estimated the
      transferred hyperfine constants for both the F(-)-Ni(2+) and the F(-)-Cd(2+)
      bonds. The values of the hyperfine constants compare well to the ones known for
      F(-)-Ni(2+) in KNiF3 and NiF2 and for F(-)-Cr(3+) in K2NaCrF6. The results are
      discussed in terms of hybridization of the 2s, 2p orbitals of the F(-) ion and
      the d orbitals of the magnetic ion. Finally, we discuss the implications of our
      results for the electron-spin decoherence.

PMID- 24735299
TI  - Static and dynamic length scales in supercooled liquids: insights from molecular
      dynamics simulations of water and tri-propylene oxide.
AB  - We perform molecular dynamics simulations to study static and dynamic length
      scales in molecular supercooled liquids, in particular, water. For a
      determination of these scales, we use equilibrium configurations and pin
      appropriate subsets of molecules so as to obtain random matrices, cylindrical
      pores, and slit confinements. Static length scales xi(s) are determined by
      analyzing overlap correlation functions for various fractions of pinned molecules
      or distances to the confining walls. For water in all confinements and for
      propylene oxide trimers in random geometry, a linear increase of xi(s) with
      inverse temperature is found. Dynamic length scales xi(d) are determined by
      analogous analysis of fraction-dependent or position-resolved correlation times
      of structural relaxation. While xi(d) continuously grows upon cooling in the
      cylindrical and slit confinements, we find no evidence for a temperature
      dependence in random matrices, implying that molecular dynamics in parsed volumes
      is qualitatively different from that in bulk liquids. Finally, we study possible
      connections between the growth of the static and dynamic length scales and the
      slowdown of the structural relaxation of the supercooled bulk liquids. For water,
      we observe a linear relation between ln tau(alpha) and xi(s)2/T in the whole
      accessible range down to the critical temperature of mode-coupling theory, T(c).
      In the weakly supercooled regime, the same relation holds also for xi(d), as
      obtained from cylindrical and slit confinements, but deviations from this
      behavior are observed near T(c). The results are discussed in connection with
      random first-order theory and experimental studies of liquid dynamics in
      nanoscopic confinements and binary mixtures.

PMID- 24735300
TI  - Anharmonicity, mechanical instability, and thermodynamic properties of the Cr-Re
      sigma-phase.
AB  - Using density-functional theory in combination with the direct force method and
      molecular dynamics we investigate the vibrational properties of a binary Cr-Re
      sigma-phase. In the harmonic approximation, we have computed phonon dispersion
      curves and density of states, evidencing structural and chemical effects. We
      found that the sigma-phase is mechanically unstable in some configurations, for
      example, when all crystallographic sites are occupied by Re atoms. By using a
      molecular-dynamics-based method, we have analysed the anharmonicity in the system
      and found negligible effects (~0.5 kJ/mol) on the Helmholtz energy of the binary
      Cr-Re sigma-phase up to 2000 K (~0.8T(m)). Finally, we show that the vibrational
      contribution has significant consequences on the disordering of the sigma-phase
      at high temperature.

PMID- 24735301
TI  - First principles calculation of a large variation in dielectric tensor through
      the spin crossover in the CsFe[Cr(CN)6] Prussian blue analogue.
AB  - The dielectric response of spin-crossover (SCO) materials is a key property
      facilitating their use in next-generation information processing technologies.
      Solid state hybrid density functional theory calculations show that the
      temperature-induced and strongly hysteretic SCO transition in the
      Cs(+)Fe(2+)[Cr(3+)(CN(-))6] Prussian blue analogue (PBA) is associated with a
      large change (Delta) in both the static, DeltaE(0)(HS - LS), and high frequency,
      DeltaE(infinity)(HS - LS) dielectric constants. The SCO-induced variation in
      CsFe[Cr(CN)6] is significantly greater than the experimental DeltaE values
      observed previously in other SCO materials. The phonon contribution,
      DeltaE(phon)(HS - LS), determined within a lattice dynamics approach, dominates
      over the clamped nuclei term, DeltaE(infinity)(HS - LS), and is in turn dominated
      by the low-frequency translational motions of Cs(+) cations within the cubic
      voids of the Fe[Cr(CN)6](-) framework. The Cs(+) translational modes couple
      strongly to the large unit cell volume change occurring through the SCO
      transition. PBAs and associated metal-organic frameworks emerge as a potentially
      fruitful class of materials in which to search for SCO transitions associated
      with large changes in dielectric response and other macroscopic properties. 

PMID- 24735302
TI  - A recipe for free-energy functionals of polarizable molecular fluids.
AB  - Classical density-functional theory is the most direct approach to equilibrium
      structures and free energies of inhomogeneous liquids, but requires the
      construction of an approximate free-energy functional for each liquid of
      interest. We present a general recipe for constructing functionals for small
      molecular liquids based only on bulk experimental properties and ab initio
      calculations of a single solvent molecule. This recipe combines the exact free
      energy of the non-interacting system with fundamental measure theory for the
      repulsive contribution and a weighted density functional for the short-ranged
      attractive interactions. We add to these ingredients a weighted polarization
      functional for the long-range correlations in both the rotational and molecular
      polarizability contributions to the dielectric response. We also perform
      molecular dynamics calculations for the free energy of cavity formation and the
      high-field dielectric response, and show that our free-energy functional
      adequately describes these properties (which are key for accurate solvation
      calculations) for all three solvents in our study: water, chloroform, and carbon
      tetrachloride. 

PMID- 24735303
TI  - Inverse melting in a two-dimensional off-lattice model.
AB  - We carry out computer simulations of a simple, two-dimensional off-lattice model
      that exhibits inverse melting. The monodisperse system comprises core-softened
      disks interacting through a repulsive square shoulder located inside an
      attractive square well. By systematically varying the potential parameters, we
      increase the pressure range over which the liquid freezes to a crystal upon
      isobaric heating. The effect is largely controlled by the extent of the shoulder.
      Despite occurring in two dimensions, the melting transition is first order and to
      a liquid, rather than to a hexatic or quasicrystal phase. We also provide comment
      on a commonly employed correlation function used to determine the degree of
      translational ordering in a system. 

PMID- 24735304
TI  - Topology and glass structure evolution in (BaO)x((B2O3)32(SiO2)68)(100-x) ternary
      -evidence of rigid, intermediate, and flexible phases.
AB  - We examine variations in the glass transition temperature (T(g)(x)), molar volume
      (V(m)(x)), and Raman scattering of titled glasses as a function of modifier (BaO)
      content in the 25% < x < 48% range. Three distinct regimes of behavior are
      observed; at low x, 24% < x < 29% range, the modifier largely polymerizes the
      backbone, T(g)(x) increase, features that we identify with the stressed-rigid
      elastic phase. At high x, 32% < x < 48% range, the modifier depolymerizes the
      network by creating non-bridging oxygen (NBO) atoms; in this regime T(g)(x)
      decreases, and networks are viewed to be in the flexible elastic phase. In the
      narrow intermediate x regime, 29% < x < 32% range, T(g)(x) shows a broad global
      maximum almost independent of x, and Raman mode scattering strengths and mode
      frequencies become relatively x-independent, V(m)(x) show a global minimum,
      features that we associate with the isostatically rigid elastic phase, also
      called the intermediate phase. In this phase, medium range structures adapt as
      revealed by the count of Lagrangian bonding constraints and Raman mode scattering
      strengths.

PMID- 24735305
TI  - Dynamical and structural properties of monohydroxy alcohols exhibiting a Debye
      process.
AB  - We perform molecular dynamics simulations to study dynamical and structural
      properties of various primary monohydroxy alcohols. Comparing rotational
      correlation functions for the individual dipole moment of the molecules and the
      total dipole moment of the system, it is shown that the studied models exhibit a
      Debye process, which is slower than the alpha process, in harmony with
      experimental results. Performing cluster analysis, it is found that hydroxyl
      groups tend to form hydrogen-bonded aggregates, in particular, chain structures,
      which are transient in nature. To ascertain a possible relation between the Debye
      process and aggregate fluctuations, we devise an algorithm allowing us to follow
      the time evolution of transient chains. It is observed that the life times of
      transient chains are substantially shorter than the correlation times of the
      Debye process, indicating that the latter relaxation is not a direct consequence
      of the chain reorganization in the studied models. We assure that this conclusion
      is not affected when hydrogen-bond cooperativity is mimicked in the simulations
      or when the polarity of the molecules and the size of the systems are varied. On
      the other hand, we find that orientational correlations of molecular dipole
      moments are not limited to hydrogen-bonded chains, but they also exist in more
      globular regions around these objects, implying that the neighboring molecules
      are polarized in the dipole field exerted by the hydrogen-bonded chains. Further
      evidence for a relevance of dipole fields comes from the observation that some
      correlation between the initial orientation of the total dipole moment and the
      instantaneous orientations of the molecular dipole moments is retained up to the
      time scale of the Debye process. The simulation results are discussed in terms of
      a La-Ola wave model with diffusive propagation. 

PMID- 24735306
TI  - Effects of excluded volume and correlated molecular orientations on Forster
      resonance energy transfer in liquid water.
AB  - Forster theory for the survival probability of excited chromophores is
      generalized to include the effects of excluded volume and orientation correlation
      in the molecular distribution. An analytical expression for survival probability
      was derived and written in terms of a few simple elementary functions. Because of
      the excluded volume, the survival probability exhibits exponential decay at early
      times and stretched exponential decay at later times. Experimental schemes to
      determine the size of the molecular excluded volume are suggested. With the
      present generalization of theory, we analyzed vibrational resonance energy
      transfer kinetics in neat water. Excluded volume effects prove to be important
      and slow down the kinetics at early times. The majority of intermolecular
      resonance energy transfer was found to occur with exponential kinetics, as
      opposed to the stretched exponential behavior predicted by Forster theory.
      Quantum yields of intra-molecular vibrational relaxation, intra-, and
      intermolecular energy transfer were calculated to be 0.413, 0.167, and 0.420,
      respectively. 

PMID- 24735307
TI  - Six-dimensional quantum dynamics study for the dissociative adsorption of DCl on
      Au(111) surface.
AB  - We carried out six-dimensional quantum dynamics calculations for the dissociative
      adsorption of deuterium chloride (DCl) on Au(111) surface using the initial state
      selected time-dependent wave packet approach. The four-dimensional dissociation
      probabilities are also obtained with the center of mass of DCl fixed at various
      sites. These calculations were all performed based on an accurate potential
      energy surface recently constructed by neural network fitting to density function
      theory energy points. The origin of the extremely small dissociation probability
      for DCl/HCl (v = 0, j = 0) fixed at the top site compared to other fixed sites is
      elucidated in this study. The influence of vibrational excitation and rotational
      orientation of DCl on the reactivity was investigated by calculating six
      dimensional dissociation probabilities. The vibrational excitation of DCl
      enhances the reactivity substantially and the helicopter orientation yields
      higher dissociation probability than the cartwheel orientation. The site-averaged
      dissociation probability over 25 fixed sites obtained from four-dimensional
      quantum dynamics calculations can accurately reproduce the six-dimensional
      dissociation probability. 

PMID- 24735308
TI  - Theory of third-order spectroscopic methods to extract detailed molecular
      orientational dynamics for planar surfaces and other uniaxial systems.
AB  - Functionalized organic monolayers deposited on planar two-dimensional surfaces
      are important systems for studying ultrafast orientational motions and structures
      of interfacial molecules. Several studies have successfully observed the
      orientational relaxation of functionalized monolayers by fluorescence
      depolarization experiments and recently by polarization-resolved heterodyne
      detected vibrational transient grating (HDTG) experiments. In this article we
      provide a model-independent theory to extract orientational correlation functions
      unique to interfacial molecules and other uniaxial systems based on polarization
      resolved resonant third-order spectroscopies, such as pump-probe spectroscopy,
      HDTG spectroscopy, and fluorescence depolarization experiment. It will be shown
      (in the small beam-crossing angle limit) that five measurements are necessary to
      completely characterize the monolayer's motions: I(?)(t) and I(?)(t) with the
      incident beams normal to the surface, I(?)(t) and I(?)(t) with a non-zero
      incident angle, and a time averaged linear dichroism measurement. Once these
      measurements are performed, two orientational correlation functions corresponding
      to in-plane and out-of-plane motions are obtained. The procedure is applicable
      not only for monolayers on flat surfaces, but any samples with uniaxial symmetry
      such as uniaxial liquid crystals and aligned planar bilayers. The theory is valid
      regardless of the nature of the actual molecular motions on interface. We then
      apply the general results to wobbling-in-a-cone model, in which molecular motions
      are restricted to a limited range of angles. Within the context of the model, the
      cone angle, the tilt of the cone relative to the surface normal, and the
      orientational diffusion constant can be determined. The results are extended to
      describe analysis of experiments where the beams are not crossing in the small
      angle limit.

PMID- 24735309
TI  - On the role of long range interactions for the adsorption of sexithiophene on
      Ag(110) surface.
AB  - The adsorption characteristics of the sexithiophene (6T) molecule on Ag(110) are
      studied using density functional theory with the inclusion of van der Waals (vdW)
      interactions. The stable adsorption configurations on 6T on Ag(110) as well as
      the nature of bonding the Ag substrate are evaluated. We also assess the
      performance of the vdW-DF method in describing the adsorption, energetics,
      heights, as well as the interface characteristics with the Ag(110) surface. We
      find two lowest adsorption energy configurations, at which the 6T molecule aligns
      with its molecular long axis parallel and perpendicular to the [001] direction,
      to be energetically close to each other, suggesting that they may coexist. Our
      findings indicate a significant increase in the 6T adsorption energies upon the
      inclusion of vdW interactions with the highest increase obtained using the opt
      type functionals, in particular with the optB86b-vdW functional. The revPBE-vdW
      and rPW86-vdW2 functionals lead to less enhancement in adsorption energies that
      is attributed to the strong repulsive nature of these functionals, in agreement
      with earlier predictions. Upon adsorption of the 6T molecule, the changes in the
      atomic and electronic structures of the 6T molecule and Ag surface are found to
      be negligible; there is no charge transfer, and no interface state is observed.
      The work function is reduced upon adsorption with the largest change is ~0.6 eV
      obtained using the optB88-vdW functional. The results are in good agreement with
      the available experimental observations of the adsorption configurations and the
      work function changes. Based on our results, we conclude that the nature of
      bonding for 6T on Ag(110) can be classified as strong physisorption.

PMID- 24735310
TI  - Influence of longitudinal isotope substitution on the thermal conductivity of
      carbon nanotubes: results of nonequilibrium molecular dynamics and local density
      functional calculations.
AB  - We report reverse nonequilibrium molecular dynamics calculations of the thermal
      conductivity of isotope substituted (10,10) carbon nanotubes (CNTs) at 300 K.
      (12)C and (14)C isotopes both at 50% content were arranged either randomly, in
      bands running parallel to the main axis of the CNTs or in bands perpendicular to
      this axis. It is found that the systems with randomly distributed isotopes yield
      significantly reduced thermal conductivity. In contrast, the systems where the
      isotopes are organized in patterns parallel to the CNTs axis feature no reduction
      in thermal conductivity when compared with the pure (14)C system. Moreover, a
      reduction of approximately 30% is observed in the system with the bands of
      isotopes running perpendicular to the CNT axis. The computation of phonon
      dispersion curves in the local density approximation and classical densities of
      vibrational states reveal that the phonon structure of carbon nanotubes is
      conserved in the isotope substituted systems with the ordered patterns, yielding
      high thermal conductivities in spite of the mass heterogeneity. In order to
      complement our conclusions on the (12)C-(14)C mixtures, we computed the thermal
      conductivity of systems where the (14)C isotope was turned into pseudo-atoms of
      20 and 40 atomic mass units. 

PMID- 24735311
TI  - Molecular dynamics study of salt-solution interface: solubility and surface
      charge of salt in water.
AB  - The NaCl salt-solution interface often serves as an example of an uncharged
      surface. However, recent laser-Doppler electrophoresis has shown some evidence
      that the NaCl crystal is positively charged in its saturated solution. Using
      molecular dynamics (MD) simulations, we have investigated the NaCl salt-solution
      interface system, and calculated the solubility of the salt using the direct
      method and free energy calculations, which are kinetic and thermodynamic
      approaches, respectively. The direct method calculation uses a salt-solution
      combined system. When the system is equilibrated, the concentration in the
      solution area is the solubility. In the free energy calculation, we separately
      calculate the chemical potential of NaCl in two systems, the solid and the
      solution, using thermodynamic integration with MD simulations. When the chemical
      potential of NaCl in the solution phase is equal to the chemical potential of the
      solid phase, the concentration of the solution system is the solubility. The
      advantage of using two different methods is that the computational methods can be
      mutually verified. We found that a relatively good estimate of the solubility of
      the system can be obtained through comparison of the two methods. Furthermore, we
      found using microsecond time-scale MD simulations that the positively charged
      NaCl surface was induced by a combination of a sodium-rich surface and the
      orientation of the interfacial water molecules. 

PMID- 24735312
TI  - Microrheology close to an equilibrium phase transition.
AB  - We investigate the microstructural and microrheological response to a tracer
      particle of a two-dimensional colloidal suspension under thermodynamic conditions
      close to a liquid-gas phase boundary. On the liquid side of the binodal,
      increasing the velocity of the (repulsive) tracer leads to the development of a
      pronounced cavitation bubble, within which the concentration of colloidal
      particles is strongly depleted. The tendency of the liquid to cavitate is
      characterized by a dimensionless "colloidal cavitation" number. On the gas side
      of the binodal, a pulled (attractive) tracer leaves behind it an extended trail
      of colloidal liquid, arising from downstream advection of a wetting layer on its
      surface. For both situations the velocity dependent friction is calculated. 

PMID- 24735313
TI  - Cooperative polymerization of one-patch colloids.
AB  - We numerically investigate cooperative polymerization in an off-lattice model
      based on a pairwise additive potential using particles with a single attractive
      patch that covers 30% of the colloid surface. Upon cooling, these particles self
      assemble into small clusters which, below a density-dependent temperature,
      spontaneously reorganize into long straight tubes. We evaluate the partition
      functions of clusters of all sizes to provide an accurate description of the
      chemical reaction constants governing this process. Our calculations show that,
      for intermediate sizes, the partition functions retain contributions from two
      different structures, differing in both energy and entropy. We illustrate the
      microscopic mechanism behind the complex polymerization process in this system
      and provide a detailed evaluation of its thermodynamics. 

PMID- 24735314
TI  - Electric-field induced alignment of nanoparticle-coated channels in thin-film
      polymer membranes.
AB  - Microscopic phase separation in immiscible polymer melts can be significantly
      altered by the presence of dispersed nanoparticles and externally applied
      electric fields. Inducing order or directionality to the resulting microstructure
      can lead to novel materials with efficient synthesis. Here, the coupled
      morphology of an immiscible binary polymer blend with dispersed nanoparticles in
      a thin-film geometry is investigated under the influence of an applied electric
      field using a unique mesoscale computational approach. For asymmetric binary
      blends (e.g., 70-30), the resulting microstructure consists of columnar channels
      of the B-phase perpendicular to the major plane of the film (aligned with the
      electric field), with the particles segregated along the channel interfaces. The
      simulations reveal the variability of the average channel diameter and the
      interfacial arrangement of the particles. The high density of exposed particles
      makes these structures viable candidates for catalytically active porous
      membranes or macromolecular manipulation devices. 

PMID- 24735316
TI  - Assembly of diblock copolymer functionalized spherical nanoparticles as a
      function of copolymer composition.
AB  - In this work, we use coarse-grained molecular dynamics simulations to study
      spherical nanoparticles functionalized with AB diblock copolymer chains at low
      grafting density, to obtain a design library linking copolymer composition,
      monomer-monomer interaction strengths, graft lengths, particle sizes, and monomer
      solvent-philicity to the two stages of nanoparticle assembly: the initial
      formation of patches within the copolymer-grafted particles from attractive
      monomers aggregating, and then the (equilibrium) assembled cluster formation.
      With regards to patch formation, as the fraction of the solvent-phobic (A or B)
      block decreases along the graft and the interaction strength decreases, the
      propensity to form patches on the particles decreases. As the fraction of the
      solvent-phobic block increases, the time for patch formation decreases, in
      particular if the inner A block is solvent-phobic. As the ratio of graft length
      to particle size increases the propensity to form fewer patches increases due to
      inter-graft monomer aggregation. For all compositions, the assembled clusters
      formed in B-selective solvents (solvent-phobic A block) have a higher fraction of
      particles at smaller inter-particle distances than in A-selective solvents
      (solvent-phobic B block). In an A-selective solvent at low interaction strengths,
      as the graft length to particle diameter ratio is increased, the tendency to form
      isotropic clusters at equilibrium is increased, and intermediate anisotropic
      chain-like assembly is observed. When these anisotropic intermediate states are
      observed, they accelerate the formation of equilibrium isotropic clusters. With
      increasing strength of interaction between solvent-phobic B monomers, the
      intermediate states disappear from the assembly pathway. At low and intermediate
      interaction strengths, as fraction of A block increases, the clusters' outer
      shell of solvent-philic A monomers which surrounds the patch of solvent-phobic B
      monomers becomes dense, hindering addition of more particles to the cluster
      leading to smaller overall clusters. In a B-selective solvent, predominantly
      anisotropic clusters form, and show an increase in shape anisotropy with
      increasing monomer interaction strength. In both cases of monomer solvent
      philicity, with an increase in the graft length to particle diameter ratio we see
      a decrease in anisotropic cluster formation. And, in both cases of monomer
      solvent philicity, with increasing monomer interaction strength the average
      cluster size and tendency to form anisotropic clusters is increased. 

PMID- 24735315
TI  - The hydrophobic effect in a simple isotropic water-like model: Monte Carlo study.
AB  - Using Monte Carlo computer simulations, we show that a simple isotropic water
      like model with two characteristic lengths can reproduce the hydrophobic effect
      and the solvation properties of small and large non-polar solutes. Influence of
      temperature, pressure, and solute size on the thermodynamic properties of apolar
      solute solvation in a water model was systematically studied, showing two
      different solvation regimes. Small particles can fit into the cavities around the
      solvent particles, inducing additional order in the system and lowering the
      overall entropy. Large particles force the solvent to disrupt their network,
      increasing the entropy of the system. At low temperatures, the ordering effect of
      small solutes is very pronounced. Above the cross-over temperature, which
      strongly depends on the solute size, the entropy change becomes strictly
      positive. Pressure dependence was also investigated, showing a "cross-over
      pressure" where the entropy and enthalpy of solvation are the lowest. These
      results suggest two fundamentally different solvation mechanisms, as observed
      experimentally in water and computationally in various water-like models. 

PMID- 24735317
TI  - Relaxation transition in glass-forming polybutadiene as revealed by nuclear
      resonance X-ray scattering.
AB  - We investigated the arrest mechanism of molecular motions in a glass forming
      polybutadiene near the glass transition using a new nuclear resonance synchrotron
      X-ray scattering technique to cover a wide time range (10(-9) to 10(-5) s) and a
      scattering vector Q range (9.6-40 nm(-1)), which have never been accessed by
      other methods. Owing to the wide time and Q ranges it was found for the first
      time that a transition of the alpha-process to the slow beta-process (or the
      Johari-Goldstein process) was observed in a Q range higher than the first peak in
      the structure factor S(Q) at the critical temperature T(c) in the mode coupling
      theory. The results suggest the important roles of hopping motions below T(c),
      which was predicted by the recent extended mode coupling theory and the
      cooperative motions due to the strong correlation at the first peak in S(Q) in
      the arrest mechanism.

PMID- 24735318
TI  - A numerical study of the phase behaviors of drug particle/star triblock copolymer
      mixtures in dilute solutions for drug carrier application.
AB  - The complex microstructures of drug particle/ABA star triblock copolymer in
      dilute solutions have been investigated by a theoretical approach which combines
      the self-consistent field theory and the hybrid particle-field theory. Simulation
      results reveal that, when the volume fraction of drug particles is smaller than
      the saturation concentration, the drug particle encapsulation efficiency is 100%,
      and micelle loading capacity increases with increasing particle volume fraction.
      When the volume fraction of drug particles is equal to the saturation
      concentration, the micelles attain the biggest size, and micelle loading capacity
      reaches a maximum value which is independent of the copolymer volume fraction.
      When the volume fraction of drug particles is more than the saturation
      concentration, drug particle encapsulation efficiency decreases with increasing
      volume fraction of drug particles. Furthermore, it is found that the saturation
      concentration scales linearly with the copolymer volume fraction. The above
      simulation results are in good agreement with experimental results. 

PMID- 24735319
TI  - Dynamics of coarsening in multicomponent lipid vesicles with non-uniform
      mechanical properties.
AB  - Multicomponent lipid vesicles are commonly used as a model system for the complex
      plasma membrane. One phenomenon that is studied using such model systems is phase
      separation. Vesicles composed of simple lipid mixtures can phase-separate into
      liquid-ordered and liquid-disordered phases, and since these phases can have
      different mechanical properties, this separation can lead to changes in the shape
      of the vesicle. In this work, we investigate the dynamics of phase separation in
      multicomponent lipid vesicles, using a model that couples composition to
      mechanical properties such as bending rigidity and spontaneous curvature. The
      model allows the vesicle surface to deform while conserving surface area and
      composition. For vesicles initialized as spheres, we study the effects of phase
      fraction and spontaneous curvature. We additionally initialize two systems with
      elongated, spheroidal shapes. Dynamic behavior is contrasted in systems where
      only one phase has a spontaneous curvature similar to the overall vesicle surface
      curvature and systems where the spontaneous curvatures of both phases are similar
      to the overall curvature. The bending energy contribution is typically found to
      slow the dynamics by stabilizing configurations with multiple domains. Such
      multiple-domain configurations are found more often in vesicles with spheroidal
      shapes than in nearly spherical vesicles. 

PMID- 24735320
TI  - CO-dynamics in the active site of cytochrome c oxidase.
AB  - The transfer of CO from heme a3 to the Cu(B) site in Cytochrome c oxidase (CcO)
      after photolysis is studied using molecular dynamics simulations using an
      explicitly reactive, parametrized potential energy surface based on density
      functional theory calculations. After photodissociation from the heme-Fe, the CO
      ligand rebinds to the Cu(B) site on the sub-picosecond time scale. Depending on
      the simulation protocol the characteristic time ranges from 260 fs to 380 fs
      which compares with an estimated 450 fs from experiment based on the analysis of
      the spectral changes as a function of time delay after the photodissociating
      pulse. Following photoexcitation ~90% of the ligands are found to rebind to
      either the Cu(B) (major component, 85%) or the heme-Fe (minor component, 2%)
      whereas about 10% remain in an unbound state. The infrared spectra of unbound CO
      in the active site is broad and featureless and no appreciable shift relative to
      gas-phase CO is found, which is in contrast to the situation in myoglobin. These
      observations explain why experimentally, unbound CO in the binuclear site of CcO
      has not been found as yet.

PMID- 24735323
TI  - Surgical stress influences cytokine content in autologous conditioned serum.
AB  - REASONS FOR PERFORMING STUDY: No recommendations have been made regarding the
      relative timing of blood collection for autologous conditioned serum (ACS)
      preparation and surgical procedures. OBJECTIVES: 1) To identify effects of
      surgical stress on cytokine levels in ACS, 2) identify haematological markers for
      prediction of cytokine production in ACS and 3) investigate the necessity for
      specialised ACS containers when preparing a cytokine-rich serum. STUDY DESIGN:
      Experimental in vitro study. METHODS: Blood was drawn from 15 stallions admitted
      for elective castration preoperatively and 22-24 h post operatively and incubated
      in ACS containers and plastic vacutainer tubes containing Z Serum Clot Activator.
      Concentrations of interleukin (IL)-1 receptor agonist (IL-1Ra), IL-10, IL-1beta,
      tumour necrosis factor (TNF)-alpha, insulin-like growth factor (IGF)-1 and
      transforming growth factor (TGF)-beta were determined in all serum samples and
      compared between preparation methods and sampling time by ANOVA. Changes in
      cytokine levels induced by incubation, defined as delta cytokine, were calculated
      by subtracting the baseline levels from the levels in incubated samples. Based on
      post operative serum amyloid A (SAA), horses were grouped into 'mild', moderate'
      and 'marked' surgical stress; delta cytokine levels in post operative samples
      were compared between these groups by ANOVA. RESULTS: Delta IGF-1 was
      significantly lower in post operative samples compared with preoperative. Horses
      in the 'marked' surgical stress group had significantly lower delta IL-1Ra and
      delta TGF-beta than the 'moderate' group and significantly lower delta IGF-1 than
      the 'mild' group. No association between cytokine levels and haematology
      variables were identified. Cytokine levels were comparable between serum prepared
      in blood tubes and in specialised ACS containers. CONCLUSIONS: Surgical stress
      influences the cytokine content in ACS. Useful predictors of cytokine production
      in ACS were not identified. Specialised ACS containers may not be necessary for
      preparation of a cytokine-rich serum.

PMID- 24735324
TI  - Quantitative analysis of macular contraction in idiopathic epiretinal membrane.
AB  - BACKGROUND: We aimed to quantify the displacement of macular capillaries using
      infrared fundus photographs and image processing software (ImageJ) in patients
      with idiopathic epiretinal membrane (ERM) who have undergone vitrectomy and to
      analyze the correlation between vessel displacement and retinal thickness.
      METHODS: This prospective study included 16 patients who underwent vitrectomy for
      idiopathic ERM. Ophthalmic examination and optical coherence tomography (OCT)
      were performed before and 3 months after surgery. The length of radial vessel
      segment included in each area (VLA) and the length from the foveola to the vessel
      branching point (FBL) depending on the superior, inferior, nasal, and temporal
      areas of the macula were measured using infrared fundus images and image
      processing software (ImageJ). Preoperative and postoperative parameters were
      compared and correlations between VLA, FBL, macular thickness, and visual acuity
      were assessed. RESULTS: The VLA of superior, inferior, and temporal areas showed
      a significant postoperative reduction. VLA differences showed a positive
      correlation with differences in macular thickness, which corresponded to the
      superior, inferior, and temporal areas; however, no correlation was observed in
      the nasal area. The FBL of the superior and inferior areas was significantly
      increased postoperatively. A positive correlation was observed between FBL
      differences and macular thickness differences in the superior area. Postoperative
      change in VLA and FBL did not show a significant correlation with postoperative
      best corrected visual acuity (BCVA) and BCVA differences. CONCLUSIONS: Infrared
      fundus photographs and image processing software can be useful for quantifying
      progressive changes in retinal surface distortion after surgical removal of ERM.
      Macular edema and vascular distortion showed significant improvement after
      surgery. Furthermore, a correlation was observed between topographic and
      tomographic changes.

PMID- 24735326
TI  - Abnormal response to the anorexic effect of GHS-R inhibitors and exenatide in
      male Snord116 deletion mouse model for Prader-Willi syndrome.
AB  - Prader-Willi syndrome (PWS) is a genetic disease characterized by persistent
      hunger and hyperphagia. The lack of the Snord116 small nucleolar RNA cluster has
      been identified as the major contributor to PWS symptoms. The Snord116 deletion
      (Snord116del) mouse model manifested a subset of PWS symptoms including
      hyperphagia and hyperghrelinemia. In this study, male Snord116del mice were
      characterized and tested for their acute and chronic responses to anorexic
      substances related to the ghrelin pathway. In comparison with their wild-type
      littermates, the food intake rate of Snord116del mice was 14% higher when fed ad
      libitum, and 32% to 49% higher within 12 hours after fasting. Fasted Snord116del
      mice were less sensitive to the acute anorexic effect of competitive antagonist
      [d-Lys(3)]-GHRP6, YIL-781, and reverse agonist [d-Arg(1),d-Phe(5),d
      Trp(7,9),Leu(11)]-substance P (SPA) of ghrelin receptor GHS-R. All 3 GHS-R
      inhibitors failed to inhibit chronic food intake of either Snord116del or wild
      type mice due to rapid adaptation. Although fasted Snord116del mice had normal
      sensitivity to the acute anorexic effect of glucagon-like peptide 1 receptor
      agonist exenatide, those fed ad libitum required a higher dose and more frequent
      delivery to achieve ~15% suppression of long-term food intake in comparison with
      wild-type mice. Ghrelin, however, is unlikely to be essential for the anorexic
      effect of exenatide in fed mice, as shown by the fact that exenatide did not
      reduce ghrelin levels in fed mice and food intake of ghrelin(-/-) mice fed ad
      libitum could be suppressed by exenatide. In conclusion, this study suggests that
      GHS-R may not be an effective therapeutic target, and in contrast, exenatide may
      produce anorexic effect in PWS individuals. 

PMID- 24735327
TI  - Impaired preadipocyte differentiation into adipocytes in subcutaneous abdominal
      adipose of PCOS-like female rhesus monkeys.
AB  - Metabolic characteristics of polycystic ovary syndrome women and polycystic ovary
      syndrome-like, prenatally androgenized (PA) female monkeys worsen with age, with
      altered adipogenesis of sc abdominal adipose potentially contributing to age
      related adverse effects on metabolism. This study examines whether adipocyte
      morphology and gene expression in sc abdominal adipose differ between late
      reproductive-aged PA female rhesus monkeys compared with age-matched controls
      (C). Subcutaneous abdominal adipose of both groups was obtained for histological
      imaging and mRNA determination of zinc finger protein 423 (Zfp423) as a marker of
      adipose stem cell commitment to preadipocytes, and CCAAT/enhancer binding protein
      (C/EBP)alpha/peroxisome proliferator-activated receptor (PPAR)delta as well as
      C/EBPalpha/PPARgamma as respective markers of early- and late-stage
      differentiation of preadipocytes to adipocytes. In all females combined, serum
      testosterone (T) levels positively correlated with fasting serum levels of total
      free fatty acid (r(2) = 0.73, P < .002). PA females had a greater population of
      small adipocytes vs C (P < .001) in the presence of increased Zfp423 (P < .025 vs
      C females) and decreased C/EBPalpha (P < .003, vs C females) mRNA expression.
      Moreover, Zfp423 mRNA expression positively correlated with circulating total
      free fatty acid levels during iv glucose tolerance testing (P < .004, r(2) =
      0.66), whereas C/EBPalpha mRNA expression negatively correlated with serum T
      levels (P < .02, r(2) = 0.43). Gene expression of PPARdelta and PPARgamma were
      comparable between groups (P = .723 and P = .18, respectively). Early-to-mid
      gestational T excess in female rhesus monkeys impairs adult preadipocyte
      differentiation to adipocytes in sc abdominal adipose and may constrain the
      ability of this adipose depot to safely store fat with age. 

PMID- 24735328
TI  - Electrophysiology of arcuate neurokinin B neurons in female Tac2-EGFP transgenic
      mice.
AB  - Neurons in the arcuate nucleus that coexpress kisspeptin, neurokinin B (NKB), and
      dynorphin (KNDy neurons) play an important role in the modulation of reproduction
      by estrogens. Here, we study the anatomical and electrophysiological properties
      of arcuate NKB neurons in heterozygous female transgenic mice with enhanced green
      fluorescent protein (EGFP) under the control of the Tac2 (NKB) promoter (Tac2
      EGFP mice). The onset of puberty, estrous cyclicity, and serum LH were comparable
      between Tac2-EGFP and wild-type mice. The location of EGFP-immunoreactive neurons
      was consistent with previous descriptions of Tac2 mRNA-expressing neurons in the
      rodent. In the arcuate nucleus, nearly 80% of EGFP neurons expressed pro-NKB
      immunoreactivity. Moreover, EGFP fluorescent intensity in arcuate neurons was
      increased by ovariectomy and reduced by 17beta-estradiol (E2) treatment.
      Electrophysiology of single cells in tissue slices was used to examine the
      effects of chronic E2 treatment on Tac2-EGFP neurons in the arcuate nucleus of
      ovariectomized mice. Whole-cell recordings revealed arcuate NKB neurons to be
      either spontaneously active or silent in both groups. E2 had no significant
      effect on the basic electrophysiological properties or spontaneous firing
      frequencies. Arcuate NKB neurons exhibited either tonic or phasic firing patterns
      in response to a series of square-pulse current injections. Notably, E2 reduced
      the number of action potentials evoked by depolarizing current injections. This
      study demonstrates the utility of the Tac2-EGFP mouse for electrophysiological
      and morphological studies of KNDy neurons in tissue slices. In parallel to E2
      negative feedback on LH secretion, E2 decreased the intensity of the EGFP signal
      and reduced the excitability of NKB neurons in the arcuate nucleus of
      ovariectomized Tac2-EGFP mice. 

PMID- 24735329
TI  - ESR1 and ESR2 differentially regulate daily and circadian activity rhythms in
      female mice.
AB  - Estrogenic signaling shapes and modifies daily and circadian rhythms, the
      disruption of which has been implicated in psychiatric, neurologic,
      cardiovascular, and metabolic disease, among others. However, the activational
      mechanisms contributing to these effects remain poorly characterized. To
      determine the activational impact of estrogen on daily behavior patterns and
      differentiate between the contributions of the estrogen receptors ESR1 and ESR2,
      ovariectomized adult female mice were administered estradiol, the ESR1 agonist
      propylpyrazole triol, the ESR2 agonist diarylpropionitrile, or cholesterol
      (control). Animals were singly housed with running wheels in a 12-hour light, 12
      hour dark cycle or total darkness. Estradiol increased total activity and
      amplitude, consolidated activity to the dark phase, delayed the time of peak
      activity (acrophase of wheel running), advanced the time of activity onset, and
      shortened the free running period (tau), but did not alter the duration of
      activity (alpha). Importantly, activation of ESR1 or ESR2 differentially impacted
      daily and circadian rhythms. ESR1 stimulation increased total wheel running and
      amplitude and reduced the proportion of activity in the light vs the dark.
      Conversely, ESR2 activation modified the distribution of activity across the day,
      delayed acrophase of wheel running, and advanced the time of activity onset.
      Interestingly, tau was shortened by estradiol or either estrogen receptor
      agonist. Finally, estradiol-treated animals administered a light pulse in the
      early subjective night, but no other time, had an attenuated response compared
      with controls. This decreased phase response was mirrored by animals treated with
      diarylpropionitrile, but not propylpyrazole triol. To conclude, estradiol has
      strong activational effects on the temporal patterning and expression of daily
      and circadian behavior, and these effects are due to distinct mechanisms elicited
      by ESR1 and ESR2 activation. 

PMID- 24735330
TI  - Regiocontrolled palladium-catalyzed arylative cyclizations of alkynols.
AB  - Tuning the reactivity of arylpalladium intermediates enables control of catalytic
      arylative 5-exo and 6-endo cyclizations of alkynols. The two modes of
      cyclizations represent a rare example of controllable, regioselective
      difunctionalization of alkynes. The cyclizations are useful in offering a
      divergent synthesis of oxygen-containing heterocycles, which is of synthetic use
      for further derivatization. Formal synthesis of an hNK-1 receptor antagonist also
      showcases the utility of our arylative cyclization. 

PMID- 24735332
TI  - Contemporary methods of body composition measurement.
AB  - Reliable and valid body composition assessment is important in both clinical and
      research settings. A multitude of methods and techniques for body composition
      measurement exist, all with inherent problems, whether in measurement methodology
      or in the assumptions upon which they are based. This review is focused on
      currently applied methods for in vivo measurement of body composition, including
      densitometry, bioimpedance analysis, dual-energy X-ray absorptiometry, computed
      tomography (CT), magnetic resonance techniques and anthropometry.
      Multicompartment models including quantification of trace elements by in vivo
      neutron activation analysis, which are regarded as gold standard methods, are
      also summarized. The choice of a specific method or combination of methods for a
      particular study depends on various considerations including accuracy, precision,
      subject acceptability, convenience, cost and radiation exposure. The relative
      advantages and disadvantages of each method are discussed with these
      considerations in mind. 

PMID- 24735333
TI  - Investigation of the peptide adsorption on ZrO2, TiZr, and TiO2 surfaces as a
      method for surface modification.
AB  - Specific surface binding peptides offer a versatile and interesting possibility
      for the development of biocompatible implant materials. Therefore, eight peptide
      sequences were examined in regard to their adsorption on zirconium oxide (ZrO2),
      titanium zircon (TiZr), and titanium (c.p. Ti). Surface plasmon resonance (SPR)
      measurements were performed on Ti coated sensor chips to determine the kinetics
      of the interactions and kinetic rate constants (kon, koff, KD, and Rmax). We also
      investigated the interactions which are present in our system. Electrostatic and
      coordinative interactions were found to play a major role in the adsorption
      process. Four of the eight examined peptide sequences showed a significant
      adsorption on all investigated materials. Moreover, the two peptides with the
      highest adsorption could be quantified (up to 370 pmol/cm(2)). For potential
      biomaterials applications, we proved the stability of the adsorption of selected
      peptides in cell culture media, under competition with proteins and at body
      temperature (37  degrees C), and their biocompatibility via their effects on the
      adhesion and proliferation of human mesenchymal stem cells (hMSCs). The results
      qualify the peptides as anchor peptides for the biofunctionalization of implants.

PMID- 24735335
TI  - Uncovering the role of intra- and intermolecular motion in frustrated Lewis
      acid/base chemistry: ab initio molecular dynamics study of CO2 binding by
      phosphorus/boron frustrated Lewis pair [tBu3P/B(C6F5)3].
AB  - The role of the intra- and intermolecular motion, i.e., molecular vibrations and
      the relative motion of reactants, remains largely unexplored in the frustrated
      Lewis acid/base chemistry. Here, we address the issue with the ab initio
      molecular dynamics (AIMD) study of CO2 binding by a Lewis acid (LA) and a Lewis
      base (LB), i.e., tBu3P + CO2 + B(C6F5)3 -> tBu3P-C(O)O-B(C6F5)3 ([1]). Reasonably
      large ensemble of AIMD trajectories propagated at 300 K from structures in the
      saddle region as well as trajectories propagated directly from the reactants
      region revealed an effect arising from significant recrossing of the saddle area.
      The effect is that transient complexes composed of weakly interacting reactants
      nearly cease to progress along the segment of the minimum energy pathway (MEP) at
      the saddle region for a (subpicosecond) period of time during which the dominant
      factor is the light-to-heavy type of relative motion of the vibrating reactants,
      i.e., the "bouncing"-like movement of CO2 with respect to much heavier phosphine
      and borane as main contributor to the mode that is perpendicular to the MEP
      direction. In terms of how P...C and B...O distances change with time, the
      roaming-like patterns of typical AIMD trajectories, reactive and nonreactive
      alike, extend far beyond the saddle region. In addition to the dynamical
      portrayal of [1], we provide the energy-landscape perspective that takes into
      account the hierarchy of time scales. The verifiable implication of the effect
      found here is that the isotopically substituted (heavier) LB/LA "pair" should be
      less reactive that the "normal" and thus lighter counterpart. 

PMID- 24735334
TI  - Association of serum Clara cell protein CC16 with respiratory infections and
      immune response to respiratory pathogens in elite athletes.
AB  - BACKGROUND: Respiratory epithelium integrity impairment caused by intensive
      exercise may lead to exercise-induced bronchoconstriction. Clara cell protein
      (CC16) has anti-inflammatory properties and its serum level reflects changes in
      epithelium integrity and airway inflammation. This study aimed to investigate
      serum CC16 in elite athletes and to seek associations of CC16 with asthma or
      allergy, respiratory tract infections (RTIs) and immune response to respiratory
      pathogens. METHODS: The study was performed in 203 Olympic athletes. Control
      groups comprised 53 healthy subjects and 49 mild allergic asthmatics. Serum
      levels of CC16 and IgG against respiratory viruses and Mycoplasma pneumoniae were
      assessed. Allergy questionnaire for athletes was used to determine symptoms and
      exercise pattern. Current versions of ARIA and GINA guidelines were used when
      diagnosing allergic rhinitis and asthma, respectively. RESULTS: Asthma was
      diagnosed in 13.3% athletes, of whom 55.6% had concomitant allergic rhinitis.
      Allergic rhinitis without asthma was diagnosed in 14.8% of athletes. Mean CC16
      concentration was significantly lower in athletes versus healthy controls and
      mild asthmatics. Athletes reporting frequent RTIs had significantly lower serum
      CC16 and the risk of frequent RTIs was more than 2-fold higher in athletes with
      low serum CC16 (defined as equal to or less than 4.99 ng/ml). Athletes had
      significantly higher anti-adenovirus IgG than healthy controls while only non
      atopic athletes had anti-parainfluenza virus IgG significantly lower than
      controls. In all athletes weak correlation of serum CC16 and anti-parainfluenza
      virus IgG was present (R = 0.20, p < 0.01). In atopic athletes a weak positive
      correlations of CC16 with IgG specific for respiratory syncytial virus (R = 0.29,
      p = 0.009), parainfluenza virus (R = 0.31, p = 0.01) and adenovirus (R = 0.27, p
      = 0.02) were seen as well. CONCLUSIONS: Regular high-load exercise is associated
      with decrease in serum CC16 levels. Athletes with decreased CC16 are more
      susceptible to respiratory infections. Atopy may be an additional factor
      modifying susceptibility to infections in subjects performing regular high-load
      exercise.

PMID- 24735336
TI  - Tuning the rotation rate of light-driven molecular motors.
AB  - Overcrowded alkenes are among the most promising artificial molecular motors
      because of their ability to undergo repetitive light-driven unidirectional rotary
      motion around the central C?C bond. The exceptional features of these molecules
      render them highly useful for a number of applications in nanotechnology. Many of
      these applications, however, would benefit from higher rotation rates. To this
      end, a new molecular motor was designed, and the isomerization processes were
      studied in detail. The new motor comprises a fluorene lower half and a five
      membered-ring upper half; the upper-half ring is fused to a p-xylyl moiety and
      bears a tert-butyl group at the stereogenic center. The kinetics of the thermal
      isomerization was studied by low-temperature UV-vis spectroscopy as well as by
      transient absorption spectroscopy at room temperature. These studies revealed
      that the tert-butyl and p-xylyl groups in the five-membered-ring upper half may
      be introduced simultaneously in the molecular design to achieve an acceleration
      of the rotation rate of the molecular motor that is larger than the acceleration
      obtained by using either one of the two groups individually. Furthermore, the new
      molecular motor retains unidirectional rotation while showing remarkably high
      photostationary states. 

PMID- 24735331
TI  - Redox and nitric oxide-mediated regulation of sensory neuron ion channel
      function.
AB  - SIGNIFICANCE: Reactive oxygen and nitrogen species (ROS and RNS, respectively)
      can intimately control neuronal excitability and synaptic strength by regulating
      the function of many ion channels. In peripheral sensory neurons, such regulation
      contributes towards the control of somatosensory processing; therefore,
      understanding the mechanisms of such regulation is necessary for the development
      of new therapeutic strategies and for the treatment of sensory dysfunctions, such
      as chronic pain. RECENT ADVANCES: Tremendous progress in deciphering nitric oxide
      (NO) and ROS signaling in the nervous system has been made in recent decades.
      This includes the recognition of these molecules as important second messengers
      and the elucidation of their metabolic pathways and cellular targets. Mounting
      evidence suggests that these targets include many ion channels which can be
      directly or indirectly modulated by ROS and NO. However, the mechanisms specific
      to sensory neurons are still poorly understood. This review will therefore
      summarize recent findings that highlight the complex nature of the signaling
      pathways involved in redox/NO regulation of sensory neuron ion channels and
      excitability; references to redox mechanisms described in other neuron types will
      be made where necessary. CRITICAL ISSUES: The complexity and interplay within the
      redox, NO, and other gasotransmitter modulation of protein function are still
      largely unresolved. Issues of specificity and intracellular localization of these
      signaling cascades will also be addressed. FUTURE DIRECTIONS: Since our
      understanding of ROS and RNS signaling in sensory neurons is limited, there is a
      multitude of future directions; one of the most important issues for further
      study is the establishment of the exact roles that these signaling pathways play
      in pain processing and the translation of this understanding into new
      therapeutics.

PMID- 24735337
TI  - Using social and behavior change communication to increase HIV testing and condom
      use: the Malawi BRIDGE Project.
AB  - While overall HIV prevalence in Malawi has decreased, it is still high in the
      southern region of the country. Behavioral prevention activities are crucial to
      continue the reduction in HIV prevalence. Behavior change is influenced by many
      factors. Previous work indicates knowledge about HIV transmission, self-efficacy
      to protect oneself from exposure, and accurate risk perception of one's
      susceptibility all impact sexual behavior. The current study looks at the effects
      of a behavior change communication program in Malawi called the BRIDGE II Project
      on psychosocial and behavioral variables. The program sought to address barriers
      to individual action and confront societal norms related to sexual risk behavior
      through a mix of community-based activities and mass media messages delivered
      through local radio stations. Using cohort data (n = 594), we examined the effect
      of BRIDGE exposure on three variables that affect HIV behaviors: knowledge, self
      efficacy, and risk perception, as well as two behavioral outcomes: HIV testing
      and condom use at last sex. Data were collected at baseline and for a midterm
      evaluation. Regression analyses showed exposure to BRIDGE was significantly
      associated with knowledge level (beta = 0.20, p < .001) and self-efficacy (beta =
      0.35, p < .001) at midterm when controlling for baseline scores, but not risk
      perception. Psychosocial variables did not show a significant relationship to
      either behavioral outcome. However, program exposure was a significant predictor
      of both HIV testing in the past year (odds ratio [OR] = 1.40, p < .001) and
      condom use at last sex (OR = 1.26, p < .05). This study suggests such a
      communication intervention may play an important role in not only affecting HIV
      related behaviors themselves, but also critical factors that affect HIV
      behaviors, including knowledge and self-efficacy. It is recommended that
      communication efforts around HIV risk reduction be increased. 

PMID- 24735338
TI  - Predictors of the pathogenicity of methicillin-resistant Staphylococcus aureus
      nosocomial pneumonia.
AB  - BACKGROUND AND OBJECTIVE: The clinical characteristics of patients with
      nosocomial pneumonia (NP) associated with methicillin-resistant Staphylococcus
      aureus (MRSA) infection are not well characterized. METHODS: Three hundred and
      thirty-seven consecutive patients with MRSA isolation from respiratory specimens
      who attended our hospital between April 2007 and March 2011 were enrolled.
      Patients characteristics diagnosed with 'true' MRSA-NP were described with
      regards to clinical, microbiological features, radiological features and genetic
      characteristics of the isolates. The diagnosis of 'true' MRSA-NP was confirmed by
      anti-MRSA treatment effects, Gram-staining or bronchoalveolar lavage fluid
      culture. RESULTS: Thirty-six patients were diagnosed with 'true' MRSA-NP, whereas
      34 were diagnosed with NP with MRSA colonization. Patients with a MRSA-NP had a
      Pneumonia Patient Outcomes Research Team score of 5 (58.3% vs 23.5%), single
      cultivation of MRSA (83.3% vs 38.2%), MRSA quantitative cultivation yielding more
      than 10(6) CFU/mL (80.6% vs 47.1%), radiological findings other than lobar
      pneumonia (66.7% vs 26.5%), and a history of head, neck, oesophageal or stomach
      surgery (30.6% vs 11.8%). These factors were shown to be independent predictors
      of the pathogenicity of 'true' MRSA-NP by multivariate analysis (P < 0.05).
      CONCLUSIONS: 'True' MRSA-NP shows distinct clinical and radiological features
      from NP with MRSA colonization.

PMID- 24735339
TI  - Association of group component genetic variations in COPD and COPD exacerbation
      in a Japanese population.
AB  - BACKGROUND AND OBJECTIVE: Vitamin D supplementation can decrease the
      vulnerability to pulmonary infections. Therefore, it is speculated that the genes
      related to vitamin D metabolism are associated with an exacerbation-prone
      phenotype in chronic obstructive pulmonary disease (COPD). Because genetic
      variations of group component (GC) affect immunological capacity and serum
      vitamin D concentration, they could also affect the susceptibility to COPD
      exacerbation and the disease progression. We investigated the association between
      GC genetic variations and COPD and its exacerbation frequency in a Japanese
      population. METHODS: We performed genotype analysis of 361 COPD patients and 219
      controls to identify two coding single nucleotide polymorphisms of GC, rs4588 and
      rs7041. We examined whether these polymorphisms were associated with the
      frequency of COPD exacerbation and analysed the correlation between the
      genotypes, COPD, emphysema severity and COPD progression, namely, the annual
      decline in airflow obstruction and diffusing capacity. RESULTS: Subjects with a C
      allele at rs4588 exhibited a higher frequency of exacerbations (P = 0.0048),
      greater susceptibility to chronic obstructive pulmonary disease (P = 0.0003), and
      emphysema (P = 0.0029), and a tendency for rapid decline of airflow obstruction
      (P = 0.0927). CONCLUSIONS: GC variations may affect exacerbation susceptibility,
      possibly leading to COPD worsening and its progression.

PMID- 24735340
TI  - Prevalence of COPD.

PMID- 24735341
TI  - Reply: To PMID 24033868.

PMID- 24735344
TI  - Queering the family? A multi-layered analysis of relations of inequality in
      transnational adoption.
AB  - This paper explores the tensions between the (equal) parental right claims in
      adopting countries and the global inequalities in class, race and geographical
      location that shape transnational adoption. It uses the story told by a Belgian
      couple who disguised their lesbian relationship from the authorities involved to
      explore the narratives of child, family and nation that undergird transnational
      adoption. The paper discusses the potential and limits of the creation of non
      traditional families for producing greater equity and significant
      reinterpretations of kinship and the family script. Moreover, taking into account
      different layers of both oppression and privilege, it discusses the ethical
      implications of the (queer) liberal ideologies of parental rights and Western
      moral superiority that prevail in transnational adoption. It argues for a shift
      away from the desire to create non-biological and/or non-heterosexual forms of
      private nuclear kinship through transnational adoption to a more profound and
      critical re-thinking of the (transnational) care of children, with space and
      acceptance for profoundly different constellations of care. 

PMID- 24735345
TI  - The effects of vaginal prolapse surgery using synthetic mesh on vaginal wall
      sensibility, vaginal vasocongestion, and sexual function: a prospective single
      center study.
AB  - INTRODUCTION: Vaginal mesh surgery in patients with pelvic organ prolapse (POP)
      has been associated with sexual dysfunction. Implantation of synthetic mesh might
      damage vaginal innervation and vascularization, which could cause sexual
      dysfunction. AIM: We aim to evaluate the effects of vaginal mesh surgery on
      vaginal vasocongestion and vaginal wall sensibility in patients with recurrent
      POP. METHODS: A prospective study was performed among patients with previous
      native tissue repair, scheduled for vaginal mesh surgery. Measurements were
      performed before and 6 months after surgery, during nonerotic and erotic visual
      stimuli, using a validated vaginal combi-probe. MAIN OUTCOME MEASURES: The combi
      probe involves vaginal photoplethysmography to assess Vaginal Pulse Amplitude
      (VPA) (representing vaginal vasocongestion) and four pulse-generating electrodes
      to measure vaginal wall sensibility (representing vaginal innervation). Sexual
      function was assessed using validated questionnaires (Female Sexual Function
      Index, Female Sexual Distress Scale-Revised, and Subjective sexual arousal and
      affect questionnaire). RESULTS: Sixteen women were included, 14 completed the 6
      month follow-up visit. Vaginal vasocongestion under erotic conditions did not
      significantly alter after mesh implantation. Vaginal wall sensibility of the
      distal posterior wall was significantly increased after mesh surgery
      (preoperative threshold 6.3 mA vs. postoperative 3.4 mA, P = 0.03). Sexual
      function as assessed with questionnaires was not significantly affected.
      CONCLUSIONS: In women with a history of vaginal prolapse surgery, vaginal mesh
      surgery did not decrease vaginal vasocongestion or vaginal wall sensibility.
      Vaginal vasocongestion prior to mesh surgery appeared to be lower than that of
      women never operated on. Apparently, native tissue repair decreased preoperative
      vaginal vasocongestion levels to such extent that subsequent mesh surgery had no
      additional detrimental effect. Our findings should be interpreted cautiously.
      Replication of the findings in future studies is essential.

PMID- 24735346
TI  - Evaluation of antinuclear antibodies by indirect immunofluorescence and line
      immunoassay methods': four years' data from Turkey.
AB  - The presence of antinuclear antibodies (ANAs), directed against intracellular
      antigens, is a hallmark of systemic autoimmune rheumatic diseases. The indirect
      immunofluorescence (IIF) assay is among the most commonly used routine methods
      for ANA detection as the screening test. The objective of the study was to
      evaluate ANA patterns in a 4-year period retrospectively. All 19 996 serum
      samples that were sent to the Laboratory of Medical Microbiology of the tertiary
      Hospital by any hospital department between 1 January 2009 and 1 January 2013
      with a request to test for ANA, anti-ENA or both were included in the study. Of
      these samples, 4375 (21.9%) were ANA-IIF-positive and 15621 (78.1%) were ANA-IIF
      negative. The presented ANA-positive samples consisted of 2392 (54.67%)
      homogenous, 818 (18.70%) speckled, 396 (9.05%) centromere, 242 (5.53%) nucleolar,
      213 (4.87%) nuclear dots, 178 (4.07%) cytoplasmic (except for actin and golgi),
      24 (0.55%) actin, 9 (0.21%) golgi, 53 (1.21%) nuclear membrane and 50 (1.14%)
      mixed pattern. Totally 7800 samples were examined by LIA. Of these samples, 3440
      were positive and 4307 were negative with IIF and LIA. In addition, 22 samples
      were detected as IIF-positive but LIA-negative, whereas the rest 31 samples were
      IIF-negative but LIA-positive. ANA patterns in 22 IIF-positive samples were
      homogenous (9), speckled (5), golgi (4), cytoplasmic (3) and nucleolar (1).
      SSA/Ro-52, SSB/La and Scl-70 positivity were detected in 31 IIF-negative/LIA
      positive samples by LIA. The present study comes forward with its overall scope,
      which covers 4-year data obtained in tertiary hospital located in the western
      part of Turkey.

PMID- 24735347
TI  - Double-wall carbon nanotubes for wide-band, ultrafast pulse generation.
AB  - We demonstrate wide-band ultrafast optical pulse generation at 1, 1.5, and 2 MUm
      using a single-polymer composite saturable absorber based on double-wall carbon
      nanotubes (DWNTs). The freestanding optical quality polymer composite is prepared
      from nanotubes dispersed in water with poly(vinyl alcohol) as the host matrix.
      The composite is then integrated into ytterbium-, erbium-, and thulium-doped
      fiber laser cavities. Using this single DWNT-polymer composite, we achieve 4.85
      ps, 532 fs, and 1.6 ps mode-locked pulses at 1066, 1559, and 1883 nm,
      respectively, highlighting the potential of DWNTs for wide-band ultrafast
      photonics. 

PMID- 24735348
TI  - Ketogenic diet therapy is effective in encephalitis with refractory seizures.
AB  - OBJECTIVE AND IMPORTANCE: Although ketogenic diet therapy is effective in
      refractory seizures in childhood, its effect on adult encephalitis with similar
      refractory seizures and prolonged encephalopathy has not been well reported.
      CLINICAL PRESENTATION: We report here a case of a 22-year-old man with acute
      encephalitis with refractory repetitive partial seizures (AERRPS). INTERVENTION:
      Partial seizures of the face developed to repeated generalized convulsions, which
      were refractory against anti-epileptic drugs and a high dose of propofol. After
      struggling for 9 months, he dramatically recovered after ketogenic diet therapy.
      CONCLUSION: Ketogenic diet therapy may be an important tool to help cure AERRPS.

PMID- 24735349
TI  - Are they too old? Surgical treatment for metastatic epidural spinal cord
      compression in patients aged 65 years and older.
AB  - OBJECTIVES: We aimed to assess the efficacy of surgical decompression of
      metastatic epidural spinal cord compression (MESCC) in patients ?65 years and
      review our multidisciplinary surgical decision-making process. METHODS: We
      identified all patients operated for MESCC from August 2008 to June 2012.
      Patients ?65 years, with a single area of cord compression, back/radicular pain,
      neurological signs of cord compression, surgery within 48 hours after onset of
      MESCC-related paraplegia, and follow-up for ?1 year or until death were included.
      Files were reviewed retrospectively. The requirement for informed consent was
      waived. Neurological status was assessed with the American Spinal Injury
      Association (ASIA) Impairment Scale (AIS). Duration of ambulation and survival
      were assessed with Kaplan-Meier and Cox regression analysis. RESULTS: Twenty-one
      patients met inclusion criteria (11 women/10 men; mean age 73 years, range 65
      87). All presented with debilitating back/neck pain. Ten patients (48%) were not
      ambulatory before surgery and four suffered urinary incontinence/constipation
      (19%). Preoperative AIS was E in 5 patients (24%), D in 11 (62%), and C in 5
      (24%). Motor symptoms had been present for a mean of 3.8 days (range 1-14). All
      patients regained ambulation. Overall, mean survival was 320 days (range 19-798)
      and mean ambulation was 302 days (range 18-747). On 31 March 2013, 7 patients
      (33%) were alive and ambulatory at a mean of 459 days (range 302-747); 14
      patients had died (67%) at a mean of 251 days (range 19-798), with a mean
      ambulation of 223 days (range 18-730). DISCUSSION: With careful patient
      selection, surgery may achieve long duration of ambulation in patients ?65 years
      with MESCC.

PMID- 24735351
TI  - Community-based first aid: a program report on the intersection of community
      based participatory research and first aid education in a remote Canadian
      Aboriginal community.
AB  - CONTEXT: Community-based first aid training is the collaborative development of
      locally relevant emergency response training. The Sachigo Lake Wilderness
      Emergency Response Education Initiative was developed, delivered, and evaluated
      through two intensive 5-day first aid courses. Sachigo Lake First Nation is a
      remote Aboriginal community of 450 people in northern Ontario, Canada, with no
      local paramedical services. These courses were developed in collaboration with
      the community, with a goal of building community capacity to respond to medical
      emergencies. ISSUE: Most first aid training programs rely on standardized
      curriculum developed for urban and rural contexts with established emergency
      response systems. Delivering effective community-based first aid training in a
      remote Aboriginal community required specific adaptations to conventional first
      aid educational content and pedagogy. LESSONS LEARNED: Three key lessons emerged
      during this program that used collaborative principles to adapt conventional
      first aid concepts and curriculum: (1) standardized approaches may not be
      relevant nor appropriate; (2) relationships between course participants and the
      people they help are relevant and important; (3) curriculum must be attentive to
      existing informal and formal emergency response systems. These lessons may be
      instructive for the development of other programs in similar settings.

PMID- 24735350
TI  - Prevalence of hypocalcaemia and its associated features in 22q11.2 deletion
      syndrome.
AB  - BACKGROUND: 22q11.2 deletion syndrome (22q11.2DS) is a relatively common yet
      under-recognized genetic syndrome that may present with endocrine features. We
      aimed to address the factors that contribute to the high prevalence of
      hypocalcaemia. METHODS: We investigated hypocalcaemia in a well-characterized
      sample of 138 adults with 22q11.2DS (65 m, 73 F; mean age 34.2, SD 11.8, years)
      using laboratory studies and lifelong medical records. Logistic regression
      modelling was used to identify features associated with lifetime prevalence of
      hypocalcaemia. RESULTS: Of the total sample, 111 (80.4%) had a lifetime history
      of hypocalcaemia. Eleven (84.6%) of 13 subjects with neonatal hypocalcaemia had
      documented recurrence of hypocalcaemia. Lifetime history of hypocalcaemia was
      associated with lifetime prevalence of hypoparathyroidism (P < 0.0001) and
      hypothyroidism (P = 0.04), as statistically independent factors. Hypomagnesaemia
      was associated with concurrent hypocalcaemic measurements, especially in the
      presence of concurrent hypoparathyroidism (P = 0.02). CONCLUSIONS: The results
      suggest that, in addition to the major effect of hypoparathyroidism,
      hypothyroidism may play a role in hypocalcaemia in 22q11.2DS and that there is a
      high recurrence rate of neonatal hypocalcaemia. Hypomagnesaemia may contribute to
      hypocalcaemia by further suppressing parathyroid hormone (PTH). Although further
      studies are needed, the findings support regular lifelong follow-up of calcium,
      magnesium, PTH and TSH levels in patients with 22q11.2DS. At any age,
      hypocalcaemia with hypoparathyroidism and/or hypothyroidism may suggest a
      diagnosis of 22q11.2DS.

PMID- 24735353
TI  - USGS48 Puerto Rico precipitation - a new isotopic reference material for delta2H
      and delta18O measurements of water.
AB  - A new secondary isotopic reference material has been prepared from Puerto Rico
      precipitation, which was filtered, homogenised, loaded into glass ampoules,
      sealed with a torch, autoclaved to eliminate biological activity, and calibrated
      by dual-inlet isotope-ratio mass spectrometry. This isotopic reference material,
      designated as USGS48, is intended to be one of two isotopic reference waters for
      daily normalisation of stable hydrogen (delta(2)H) and stable oxygen (delta(18)O)
      isotopic analysis of water with a mass spectrometer or a laser absorption
      spectrometer. The delta(2)H and delta(18)O values of this reference water are
      2.0+/-0.4 and-2.224+/-0.012 0/00, respectively, relative to Vienna Standard Mean
      Ocean Water on scales normalised such that the delta(2)H and delta(18)O values of
      Standard Light Antarctic Precipitation reference water are-428 and-55.5 0/00,
      respectively. Each uncertainty is an estimated expanded uncertainty (U=2u(c))
      about the reference value that provides an interval that has about a 95 %
      probability of encompassing the true value. This isotopic reference water is
      available by the case of 144 glass ampoules containing 5 mL of water in each
      ampoule.

PMID- 24735352
TI  - Epidemiology of respiratory symptoms in children with Down syndrome: a nationwide
      prospective web-based parent-reported study.
AB  - BACKGROUND: Children with Down syndrome suffer from recurrent respiratory tract
      and ear-nose-throat complaints that influence daily life. Little is known about
      the frequency of these complaints, as well as their relation to co-morbidity and
      ageing. METHODS/DESIGN: A prospective web-based parent-reported observational
      study was designed for parents having a child with Down syndrome (age 0 to 18
      years). Upon registration, parents receive an email containing a link to a weekly
      questionnaire regarding respiratory symptoms during two consecutive years.
      Additionally, at the beginning, after one year and at the end of the study they
      receive an extended questionnaire concerning baseline data, daily activities and
      medical history. The data will be compared to the ongoing "child-is-ill" study,
      which collects weekly data in an identical fashion in children that are
      considered to be "normal as to being ill" by their parents. DISCUSSION: This
      study will provide important data on the epidemiology of respiratory symptoms in
      children with Down syndrome, which will be useful for further studies on
      treatment options. Also, this study will gain insight in healthcare usage and
      work absence due to the child's illnesses.

PMID- 24735355
TI  - Construction of homoallylic alcohols from terminal alkynes and aldehydes with
      installation of syn-stereochemistry.
AB  - A cationic rhodium(I) catalyst turns 2-silyl-1-alkenylboronate, readily prepared
      from a terminal alkyne, into the corresponding allylboronate species, which
      immediately undergoes nucleophilic addition to an aldehyde to give a syn
      homoallylic alcohol stereoselectively. 

PMID- 24735354
TI  - Increase in child behavior problems among urban Brazilian 4-year olds: 1993 and
      2004 Pelotas birth cohorts.
AB  - BACKGROUND: There are an increasing number of reports on time trends in child and
      adolescent psychological problems but none from low- and middle-income countries,
      and very few covering the preschool period. The aim was to investigate changes in
      preschool behavioral/emotional problems in two birth cohorts from a middle-income
      country born 11 years apart. METHODS: We analyzed data from the 1993 and 2004
      Pelotas birth cohort studies from Brazil. A subsample of 4-year olds from the
      1993 cohort (634) and all 4-year olds from the 2004 cohort (3750) were assessed
      for behavioral/emotional problems through maternal report using the Child
      Behavior Checklist (CBCL). Response rates in these two population-based cohorts
      were above 90%. RESULTS: We found a significant increase in CBCL total problems,
      internalizing and externalizing mean scores over the 11-year period. For 1993 and
      2004 Pelotas cohorts, respectively, CBCL mean values (SE) total problems scores
      were 27.9 (0.8) and 34.7 (0.3); for internalizing scores, 5.7 (0.2) and 6.3 (0.1)
      and for externalizing scores, 12.4 (0.4) and 15.5 (0.1). After adjusting for
      confounding variables, the largest increase from 1993 to 2004 was identified in
      the aggressive behavior syndrome score (Cohen's d = .50), followed by the
      externalizing problem score (Cohen's d = .40) and CBCL total problem score
      (Cohen's d = .36), respectively. The rise in child psychological problems was
      more marked in children from families with fewer assets and with less educated
      mothers. CONCLUSIONS: Our findings provide evidence for a substantial increase in
      preschool behavioral problems among children in Brazil over an 11-year period.

PMID- 24735356
TI  - K-H3C and K-Sn interactions in potassium trimethylstannyl complexes: a
      structural, mechanochemical, and NMR study.
AB  - A series of trimethylstannyl potassium complexes [K(L)SnMe3] with different
      auxiliary ligands L (L = 18-C-6, (TMEDA)2 (TMEDA = tetramethylethylenediamine),
      and (12-C-4)2) were synthesized by alkoxide-induced B-Sn bond cleavage. X-ray
      structure determinations were performed for all these complexes, and the
      structural chemistry was studied in detail. For L = 18-C-6 and (TMEDA)2 the solid
      state structures comprise polymeric [K(L)SnMe3]n chains containing bidentate
      trimethylstannyl anions bridging two [K(L)](+) ions, featuring unsymmetrical
      coordination of the [K(L)](+) ion by K-Sn and K-H3C interactions as a central
      structural motif. In contrast, for L = (12-C-4)2, separated [K(12-C-4)2](+) and
      [SnMe3](-) ions are observed. Unexpectedly, in the presence of tetrahydrofuran
      (THF), [K(18-C-6)SnMe3]n forms upon crystallization a new species consisting of
      separated [K(18-C-6)(THF)2](+) and [(Me2SnCH3)K(18-C-6)SnMe3](-) ions. In this
      unsymmetrical anion two trimethylstannyl anions coordinate a single [K(18-C
      6)](+) ion; one trimethylstannyl anion coordinates via a K-Sn interaction, and
      the second coordinates via a K-H3C interaction. Simulations of the
      mechanochemical properties (compliance constants) applying approximated density
      functional theory revealed that both interactions are very soft and are of
      comparable strength. Moreover, according to our gas phase simulations the
      unsymmetrically coordinated [(Me2SnCH3)K(18-C-6)SnMe3](-) is indeed
      thermodynamically favored over both possible symmetrical isomers with either K-Sn
      or K-H3C coordination. Furthermore, the existence of multiple species due to the
      two coordination modes and aggregates of [K(18-C-6)SnMe3] in solution is
      suggested by NMR spectroscopic studies using (1)H, NOESY/ROESY, and (1)H pulsed
      field gradient diffusion experiments. 

PMID- 24735357
TI  - Role of cardiolipin in mitochondrial diseases and apoptosis.
AB  - Apoptosis is a highly programmed cell death strictly connected to the
      pathogenesis of many human diseases, including neoplastic, neurodegenerative or
      cardiovascular diseases. Mitochondria play a key role in the apoptotic process;
      their damage activates a series of events which provoke the release of cytochrome
      c and other pro-apoptotic factors from the mitochondrial intermembrane space, and
      culminate in cell death. This review provides an overview of the key role played
      by mitochondria in the activation of the apoptotic process. In particular, the
      interest is focused on the role played by cardiolipin, a phospholipid deeply
      involved in the first steps of the process culminating in cell apoptosis.
      Mitochondrial phospholipids are involved in several cellular functions, such as
      cell respiration, apoptosis, and autophagy. Therefore, any alteration in the
      production of phospholipids or in their structural properties causes deep effects
      on the cell behavior and induces the arising of different pathologies. The
      present review summarizes the most recent advances in the study of the role that
      CL, a phospholipid possessing a unique structure, plays in mitochondrial
      activity, in apoptosis, and in the onset of human diseases.

PMID- 24735358
TI  - bHLH Transcription factors inhibitors for cancer therapy: general features for in
      silico drug design.
AB  - Numerous basic-helix-loop-helix (bHLH) transcription factors (TF) have been found
      to play important roles in tumor growth and progression. Elucidation of the
      common features of these TFs can pave the road to possible therapeutic
      intervention. The existing studies of possible inhibition of these TFs are
      concentrated on the development of peptides or small molecules that inhibit their
      dimerization or prevent their DNA binding. The bHLH TFs have striking similarity
      in many functionally important regions, such as the helical regions of TFs that
      interact with each other during dimerization and have complementary sets of
      residues on both sides of a dimer. These are hydrophobic residues along with
      anionic and cationic residues with complementary charges. Such complementarity
      also exists in other contact regions of the bHLH TFs. They also have a very
      specific set of positively charged residues on the surface, which would contact
      DNA. Such specificity defines a common concept for an in silico design of bHLH
      TFs inhibitors for a number of existing and important cancer-related TFs. 

PMID- 24735359
TI  - Inflammation, high density lipoprotein and endothelium.
AB  - High density lipoprotein (HDL) has two important roles: a) it modulates
      inflammation, and, b) it promotes reverse cholesterol transport. HDL-cholesterol
      levels are inversely correlated with the risk of cardiovascular events. The main
      component of HDL, apolipoprotein A-I (apo A-I), is largely responsible for
      reverse cholesterol transport through the macrophage ATP-binding cassette
      transporter ABCA1. Apo A-I can be damaged by oxidative mechanisms, which render
      the protein less able to promote cholesterol efflux. HDL also contains a number
      of other proteins that are affected by the oxidative environment of the acute
      phase response. Modification of the protein components of HDL can convert it from
      an anti-inflammatory to a pro inflammatory and dysfunctional particle. Small
      peptides that mimic some of the properties of apo A-I have been shown in
      preclinical models to improve HDL function and reduce atherosclerosis without
      altering HDL-cholesterol levels. Endothelium is the interface between the blood
      and the extra vascular environment regulating the traffic of vital molecules
      between the blood and tissues. Oxidative stress and excess levels of reactive
      oxygen species disrupt the normal function of endothelium. HDL and other
      antioxidant/anti-inflammatory systems prevent endothelial dysfunction and
      maintain the critical balance needed for normal vascular function. 

PMID- 24735360
TI  - New drugs for HDL-C disorders: the beginning.
AB  - For more than 20 years there has been increasing interest in the development of
      novel therapies to raise levels of high-density lipoprotein cholesterol (HDL-C).
      However, well publicized failures of recent clinical trials of agents that raise
      HDL-C levels have stimulated considerable controversy with regard to the
      potential clinical utility of this therapeutic target. A number of classes of
      agents are currently under investigation with variable effects on HDL quantity
      and quality. These will be reviewed. 

PMID- 24735361
TI  - Chronic kidney disease - different role for HDL?
AB  - Chronic kidney disease (CKD) is an emerging health hazard, connected to very high
      cardiovascular mortality due to accelerated atherosclerosis. Increased
      cardiovascular risk cannot be explained only by traditional risk factors.
      Patients with renal dysfunction have significant disturbances in lipoprotein
      metabolism and HDL in these patients becomes dysfunctional. It has been
      documented that in patients with CKD lower plasma level of HDL cholesterol and
      reduced ability of HDL to bind to ABCA1 are seen, which result in slowing down
      the reverse cholesterol transport and disturbances in HDL maturation due to
      decreased lecithin cholesterol ester transfer protein. Studies demonstrated that
      HDL of CKD patients loses its vasoprotective, antioxidative and anti-inflammatory
      properties and turns into a noxious particle which promotes endothelial
      dysfunction via stimulating superoxide production and limiting NO
      bioavailability. Alterations of HDL at the 'molecular and functional level' are
      also seen in renal transplant recipients even in those with excellent graft
      function. 

PMID- 24735362
TI  - Subfractions and subpopulations of HDL: an update.
AB  - High-density lipoproteins (HDL) are classified as atheroprotective because they
      are involved in transport of cholesterol to the liver, known as "reverse
      cholesterol transport (RCT)" exerting antioxidant and anti-inflammatory
      activities. There is also evidence for cytoprotective, vasodilatory,
      antithrombotic, and anti-infectious activities for these lipoproteins. HDLs are
      known by structural, metabolic and biologic heterogeneity. Thus, different
      methods are able to distinguish several subclasses of HDL. Different separation
      techniques appear to support different HDL fractions as being atheroprotective or
      related with lower cardiovascular (CV) risk. However, HDL particles are not
      always protective. Modification of constituents of HDL particles (primarily in
      proteins and lipids) can lead to the decrease in their activity and induce
      proatherogenic properties, especially when isolated from patients with augmented
      systemic inflammation. According to available studies, it seems that HDL
      functionality may be a better therapeutic target than HDL cholesterol quantity;
      however, it is still disputable which subfractions are most beneficial. There is
      mounting evidence supporting HDL subclasses as an important biomarker to predict
      and/or reduce CV risk. In this review we discuss recent notices on
      atheroprotective and functional characteristic of different HDL subfractions.
      Also, we provide a brief overview of the different methods used by clinicians and
      researchers to separate HDL subfractions. Ongoing and future investigations will
      yield important new information if any given separation method might represent a
      'gold standard', and which subfractions are reliable markers of CV risk and/or
      potential targets of novel, more focused, and effective therapies. 

PMID- 24735363
TI  - Targeting platinum resistant disease in ovarian cancer.
AB  - Ovarian cancer is an extremely aggressive disease in which the vast majority of
      patients face a very poor prognosis. Although most patients initially respond to
      current chemotherapeutic regimens that include a combination of platinum- based
      therapy (cisplatin/carboplatin) and paclitaxel, the vast majority of them quickly
      relapse and develop increased resistance to available treatments. Thus, intrinsic
      and acquired chemotherapy resistance is a major obstacle in the treatment of
      ovarian cancer patients. Consequently, the priorities for basic and translational
      ovarian cancer research need to include the identification of novel therapies
      directed against key molecular targets and signaling pathways in platinum
      resistant disease. At the same time, we need to develop novel systems for drug
      delivery aimed at increasing the efficacy and reducing the toxicity of platinum
      based treatments. Improving the current responses to platinum chemotherapy is
      critical not only for achieving a better outcome clinically, including a longer
      survival, but also for allowing patients to have a better quality of life while
      in treatment. 

PMID- 24735364
TI  - Mechanism of cancer drug resistance and the involvement of noncoding RNAs.
AB  - Drug resistance is one of the major reasons for the failure of cancer therapies.
      Although our understanding of resistance to targeted cancer drugs remains
      incomplete, new and more creative approaches are being exploited to intercept
      this phenomenon. Considerable advances have been made in our understanding that
      cancer drug resistance can be caused by alterations of drug efflux, increases in
      drug metabolism, mutations of drug targets, alterations in DNA repair and cell
      cycle, changes in cell apoptosis and autophagy, induction of epithelial
      mesenchymal transition (EMT) and the generation of cancer stem cells (CSCs).
      Furthermore, intracellular signalling pathways have been shown to play key
      physiological roles and the abnormal activation of signalling pathways may be
      correlated with drug resistance. Recently, noncoding RNAs (ncRNAs), including
      microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), have emerged as important
      regulators of gene expression and alternative splicing, which provides cells with
      yet another mode to greatly increase regulatory complexity and fine-tune their
      transcriptome and can rapidly adjust their proteome in response to stimuli.
      Consequently, a wide variety of biological functions have been shown to depend on
      the coordinated interactions between noncoding RNAs and cellular signalling
      networks to achieve a concerted desired physiological outcome, whereas mutations
      and dysregulation of ncRNAs have been linked to diverse human diseases, including
      cancer drug resistance. In this review, we will discuss recent findings on the
      multiple molecular roles of regulatory ncRNAs on the signalling pathways involved
      in cancer drug resistance and the therapeutic potential of reverse drug
      resistance. 

PMID- 24735365
TI  - Four major factors regulate phosphatidylinositol 3-kinase signaling pathway in
      cancers induced by infection of human papillomaviruses.
AB  - Epidemiological surveys and molecular studies have indicated that infection of
      human papillomavirus (HPV)itself is necessary but insufficient for completing
      transformation of the human epithelial cells in vivo to lead to different
      cancers. Mounting evidence exists that HPV E6/E7 oncoproteins indeed alter the
      cellular and molecular events in their transformed cells to induce cancers
      through a phosphatidylinositol 3-kinase (PI3K)/AKT/mammalian target of rapamycin
      (mTOR) signaling pathway. The PI3K/AKT/mTOR signaling pathway is, nonetheless, of
      the central importance, which tightly modulates many cellular events that occur
      in cells to lead them to be cancerous under the action of oncogenic factors. The
      cancinogenic roles of the PI3K/AKT/mTOR signaling in HPV-induced cancers are
      generally regulated by different upstream signaling molecules such as upstream
      receptor tyrosine kinases. In this article, we review that the four major
      upstream signaling molecules (growth factor receptor, notch receptor, Ras and
      PI3KCA genes) regulate PI3K/AKT/mTOR pathway to confer oncogenicity in HPV
      immortalized epithelial cells and various transformed phenotypes. 

PMID- 24735366
TI  - HIF-1 signaling in drug resistance to chemotherapy.
AB  - Activation of hypoxia-inducible factor 1 (HIF-1) signaling is observed in a broad
      range of human cancers due to tumor hypoxia and epigenetic mechanisms. HIF-1
      activation leads to the transcription of a plethora of target genes that promote
      physiological changes associated with therapeutic resistance, including the
      inhibition of apoptosis and senescence and the activation of drug efflux and
      cellular metabolism. As a result, targeting HIF-1 represents an attractive
      strategy to enhance the efficacy of current therapies as well as reduce
      resistance to chemotherapy in tumors. Approaches to inhibit HIF-1 signaling have
      primarily focused on reducing HIF-1alpha protein levels, by inducing its
      degradation or inhibiting its transcription, inhibiting HIF-1-mediated
      transcription, or disrupting the formation of the HIF-1 transcription factor
      complex. To date, multiple preclinical and clinical agents have been identified
      that effectively inhibit HIF-1 activity through various mechanisms, likely
      accounting for a portion of their anti-tumor efficacy. This review aims to
      provide an overview of our current understanding of the role of HIF-1 in
      therapeutic resistance and discuss the ongoing effort to develop HIF-1 inhibitors
      as an anti-cancer strategy. 

PMID- 24735367
TI  - IL-6 activated JAK/STAT3 pathway and sensitivity to Hsp90 inhibitors in multiple
      myeloma.
AB  - Modern anti-cancer treatment involves targeted therapy that aims at inactivating
      particular oncoproteins or signaling pathways in a cancer-type-specific manner. A
      number of potent targeted therapies affecting oncogenic kinases or receptor
      tyrosine kinases have revolutionized anti-cancer treatment. These drugs
      inactivate signaling pathways that cancer cells depend on and therefore inhibit
      their proliferation and survival. Molecular chaperones of the Hsp90 family (heat
      shock protein 90) support the integrity, folding and function of many proteins
      involved in proliferation, survival, DNA damage and repair. Hsp90 proteins are
      thus required to maintain activity of a large variety of oncogenic proteins,
      including members of the JAK/STAT and the PI3K pathways. Accordingly cancer cells
      rely on Hsp90 proteins and their expression is often elevated in malignant cells.
      In line with this, inhibitors of Hsp90 (Hsp90-Is) have demonstrated potent
      antitumor activity in preclinical studies. While Hsp90-Is can be considered as
      targeted therapy, their broad effects on multiple signaling pathways make it
      difficult to predict the therapeutic outcome. Multiple myeloma (MM) is one of the
      tumor types with elevated Hsp90 levels. Hsp90-Is demonstrated promising activity
      in preclinical studies of MM and in several clinical trials. However, large
      variability in response questioned the use of Hsp90-Is as single drugs in the
      treatment of myeloma. A critical factor in targeted therapies, including Hsp90
      Is, is identification of susceptible subgroups of patients. Predictive biomarkers
      in each particular tumor type are important in order to use anti-cancer drugs in
      a rational way. Interestingly, levels of Hsp90 expression has not proven to be
      decisive for treatment response and hence stratification of myeloma patients.
      Others and we have recently found that MM cells with an IL-6-activated JAK/STAT3
      pathway are particularly sensitive to Hsp90-Is. In this review we will discuss
      these findings, both in terms of molecular mechanisms and applications for
      selection of MM patients amenable to Hsp90-I treatment in an individually
      targeted treatment strategy. 

PMID- 24735368
TI  - Targeting drug-resistant prostate cancer with dual PI3K/mTOR inhibition.
AB  - The phosphatidylinositol-3-kinase (PI3K)/Akt/mTOR pathway is one of the most
      frequently activated signaling pathways in prostate cancer cells, and loss of the
      tumor suppressor PTEN and amplification of PIK3CA are the two most commonly
      detected mechanisms for the activation of these pathways. Aberrant activation of
      PI3K/Akt/mTOR has been implicated not only in the survival and metastasis of
      prostate cancer cells but also in the development of drug resistance. As such,
      selective inactivation of this pathway may provide opportunities to attack
      prostate cancer from all fronts. However, while preclinical studies examining
      specific inhibitors of PI3K or mTOR have yielded promising results, the evidence
      from clinical trials is less convincing. Emerging evidence from the analyses of
      some solid tumors suggests that a class of dual PI3K/mTOR inhibitors, which bind
      to and inactivate both PI3K and mTOR, may achieve better anti-cancer outcomes. In
      this review, we will summarize the mechanisms of action of these inhibitors,
      their effectiveness when used alone or in combination with other chemotherapeutic
      compounds, and their potential to serve as the next generation therapies for
      prostate cancer patients, particularly those who are resistant to the frontline
      chemotherapeutic drugs. 

PMID- 24735369
TI  - Activation of PI3K/Akt/mTOR pathway and dual inhibitors of PI3K and mTOR in
      endometrial cancer.
AB  - Endometrial cancer is the third most common cancer in women. Endometrial
      carcinomas (EC) are clinic histologically classified into two types. Type I
      tumours, which account for 80% of ECs, are estrogen-dependent and are low grade.
      Type II tumours are more aggressive with invasion into myometrium. Recently a new
      classification for endometrial cancer has been proposed based on molecular
      markers. Whether this classification is helpful for clinical management of
      endometrial cancer remains to be tested. At present, treatment outcomes of
      endometrial cancer are not satisfactory. Therefore, more effective approaches are
      sought. This review summarizes the recent studies about activation of PI3K/Akt
      pathway in EC and therapeutic implications of the inhibitors of the pathways with
      emphasis on dual inhibitors of PI3K and mTOR. Both genetic defects and
      environmental factors are involved in carcinogenesis and progression of EC via
      activation of multiple signal pathways including the PI3K/Akt pathway. Mutations
      of major components of the PI3K/Akt pathway are common in EC. Type I tumours
      usually have mutations in Ras, PTEN, PIK3CA, AKT1, beta-catenin and type II
      tumours have mutations in TP53. Environmental factor like obesity can also
      activate the PI3K/Akt pathway to increase the incidence of EC and to cause poorer
      prognosis. Therefore, inhibition of the PI3K/Akt pathway can be used for therapy
      of the disease. At present, mTOR inhibitors have been extensively studied and
      tested in clinical trials. A newly synthesised dual inhibitor of PI3K and mTOR
      BEZ235 has been shown to be more effective than mTOR inhibitor rapamycin. BEZ235
      can inhibit feedback activation of PI3K/Akt pathway by rapamycin. It is promising
      to include effective PI3K/Akt inhibitors in current treatment regime of
      endometrial cancer to improve the therapeutic efficacy. 

PMID- 24735370
TI  - Critical appraisal of ischemic stroke pathophysiology: road to cerebral
      resuscitation? part II.

PMID- 24735371
TI  - Reversible, self cross-linking nanowires from thiol-functionalized polythiophene
      diblock copolymers.
AB  - Poly(3-hexylthiophene)-block-poly(3-(3-thioacetylpropyl) oxymethylthiophene)
      (P3HT)-b-(P3TT) diblock copolymers were synthesized and manipulated by solvent
      induced crystallization to afford reversibly cross-linked semiconductor
      nanowires. To cross-link the nanowires, we deprotected the thioacetate groups to
      thiols and they subsequently oxidized to disulfides. Cross-linked nanowires
      maintained their structural integrity in solvents that normally dissolve the
      polymers. These robust nanowires could be reduced to the fully solvated polymer,
      representing a novel, reversible cross-linking procedure for functional P3HT
      based nanowire fibrils. Field-effect transistor measurements were carried out to
      determine the charge transport properties of these nanostructures. 

PMID- 24735372
TI  - Similarity of body size in queens of the wood ant Formica aquilonia from optimal
      and sub-optimal habitats indicates a strong heritable component.
AB  - Body size in animals is affected by both genes and the environment (e.g., the
      amount of food resources). In ants, body size is related to several traits in an
      individual's physiology and life history. For example, a large queen may increase
      offspring production, thus increasing her overall fitness. In this study, whether
      sub-optimal environmental conditions affect the body size of queens of the red
      wood ant, Formica aquilonia Yarrow (Hymenoptera: Formicidae). The sizes (head
      width in mm) of virgin queens, i.e., gynes, originating from forest interiors
      (resource rich) and from commercial forest clear-cuts (resource poor) were
      measured. No differences in the body size of the queens from the two habitats
      were found. In addition, the within-nest variation in queen size was similar
      between habitat types. The results indicate that the body size variation of F.
      aquilonia queens is not sensitive to environmental variation, unlike F. aquilonia
      workers. The lack of environmental variation in queen size in F. aquilonia may be
      due to a strong selection in the past to monomorphic size in this obligately
      polygynous (multi-queened) species.

PMID- 24735373
TI  - Evidence to practice commentary new evidence in coaching interventions.

PMID- 24735375
TI  - Is preoccupation an oversimplification? A call to examine cognitive factors
      underlying internet gaming disorder.

PMID- 24735374
TI  - Bifidobacterium breve and Lactobacillus rhamnosus treatment is as effective as
      budesonide at reducing inflammation in a murine model for chronic asthma.
AB  - BACKGROUND: Asthma is estimated to affect as many as 300 million people worldwide
      and its incidence and prevalence are rapidly increasing throughout the world,
      especially in children and within developing countries. Recently, there has been
      a growing interest in the use of potentially beneficial bacteria for allergic
      diseases. This study is aimed at exploring the therapeutic effects of long-term
      treatment with two different beneficial bacterial strains (Bifidobacterium breve
      M-16 V and Lactobacillus rhamnosus NutRes1) and a glucocorticoid (budesonide), as
      a reference treatment, on inflammatory response in a murine model for chronic
      allergic asthma. METHODS: To mimic the chronic disease in asthmatic patients, we
      used the murine ovalbumin-induced asthma model combined with prolonged allergen
      exposure. Airway function; pulmonary airway inflammation; airway remodelling,
      mRNA expression of pattern recognition receptors, Th-specific cytokines and
      transcription factors in lung tissue; mast cell degranulation; in vitro T cell
      activation; and expression of Foxp3 in blood Th cells were examined. RESULTS:
      Lactobacillus rhamnosus reduced lung resistance to a similar extent as budesonide
      treatment in chronically asthmatic mice. Pulmonary airway inflammation, mast cell
      degranulation, T cell activation and airway remodelling were suppressed by all
      treatments. Beneficial bacteria and budesonide differentially modulated the
      expression of toll-like receptors (TLRs), nod-like receptors (NLRs), cytokines
      and T cell transcription factors. Bifidobacterium breve induced regulatory T cell
      responses in the airways by increasing Il10 and Foxp3 transcription in lung
      tissue as well as systemic by augmenting the mean fluorescence intensity of Foxp3
      in blood CD4+ T cells. CONCLUSION: These findings show that Bifidobacterium breve
      M-16 V and Lactobacillus rhamnosus NutRes1 have strong anti-inflammatory
      properties that are comparable to budesonide and therefore may be beneficial in
      the treatment of chronic asthma.

PMID- 24735376
TI  - Biology of the malaria parasite--on the special issue for the 10th BioMalPar
      conference.

PMID- 24735377
TI  - High concentrate:forage ratio diet inhibiting omasal epithelium growth is
      associated with decreased cyclin D1 and CDK4 expression in growing goats.
AB  - The hypothesis that different concentrate : forage ratio diets alter omasal
      epithelium proliferation of growing goats via cyclins and regulation of the cell
      cycle was tested. Growing goats were fed with a high concentrate (HC, n = 8) or a
      low concentrate (LC, n = 8) diet for 42 days. The concentrate : forage ratio was
      40:60 in the HC group and 0:100 in the LC group. In the HC group, the relative
      weight and DNA content of the omasal epithelium were lower, but the protein : DNA
      ratio was higher. Flow cytometry revealed that HC omasal cell numbers were
      smaller in S- and G2 /M-phases of the cell cycle and higher in the G0 /G1 -phases
      and were accompanied by reduced expression of cyclin D1 and CDK4 mRNA and
      protein. These data are consistent with morphologic observations in the HC that
      cell density decreased in the stratum spinosum (SS) plus stratum granulosum (SG)
      and stratum basale, and that cell density was lower in the SS plus SG. Thus, high
      concentrate : forage ratio diet retards omasal epithelial growth by slowing the
      G1 to S phase transition of the cell cycle and is associated with decreased
      cyclin D1 and CDK4 expression in growing goats. 

PMID- 24735379
TI  - Synthetic and biological studies of phaeosphaerides.
AB  - The signal transducer and activator of transcription 3 (STAT3) has been validated
      as a suitable target for cancer therapy. Recent evidence by our group and others
      has shown that phaeosphaerides act as inhibitors of the STAT3 pathway. An
      efficient synthetic sequence to phaeosphaeride 1a has been previously disclosed.
      In this work, the first total synthesis of (+/-)-phaeosphaeride B (1d) and the
      unnatural phaeosphaeride 1b is reported. Additionally, the biological activities
      of 1a and 1b were investigated. (6S,7S,8S)-1a and (6R,7S,8S)-1b inhibited
      granulocyte colony-stimulating factor (GCSF)-stimulated phosphorylation of STAT1,
      STAT3, and STAT5 and IL-6-stimulated nuclear translocation of STAT3 alpha. In an
      SPR-based assay, (6S,7S,8S)-1a and (6R,7S,8S)-1b showed minimal ability to
      inhibit binding of STAT3 to its immobilized phosphotyrosylpeptide ligand (IC50 >
      100 MUM). Thus, (6S,7S,8S)-1a and (6R,7S,8S)-1b are likely upstream inhibitors of
      a kinase in the STAT signaling pathway and do not act through the inhibition of
      STAT3 dimerization by the blocking of the SH2 binding domain. 

PMID- 24735380
TI  - The 'nonmenstrual woman' in the new millennium? Discourses on menstrual
      suppression in the first decade of extended cycle oral contraception use in
      Canada.
AB  - In the early-twenty-first century, extended cycle oral contraception (ECOC)
      became available by physician prescription in North America. Researchers
      speculate that this drug, with its capacity to reduce or eliminate menstrual
      bleeding, may shift not only women's biological processes but also their
      experiences of menstruation. In this paper, I discuss women's experiences of
      menstrual suppression drawing on findings from a qualitative study conducted
      before ECOC was available, and examine these findings against recently published
      research on menstrual suppression in an ECOC era. Findings suggest that the body
      as a natural entity figures strongly in women's discourses on suppression. They
      further suggest that suppression is a contingent, paradoxical and practical
      achievement, not a securely or fully realised embodied state. This paper reads
      women's accounts of menstrual suppression prior to ECOC as a challenge to the
      modern artifice of a mind/body split, and questions whether this challenge is
      perhaps made less discernible in an ECOC era, where attention may no longer be
      paid to the daily practices of menstrual suppression. Hence, a case is made for
      the varied political effects of ongoing non-menstruation versus event-specific
      practices of non-menstruation. 

PMID- 24735378
TI  - U3 region in the HIV-1 genome adopts a G-quadruplex structure in its RNA and DNA
      sequence.
AB  - Genomic regions rich in G residues are prone to adopt G-quadruplex structure.
      Multiple Sp1-binding motifs arranged in tandem have been suggested to form this
      structure in promoters of cancer-related genes. Here, we demonstrate that the G
      rich proviral DNA sequence of the HIV-1 U3 region, which serves as a promoter of
      viral transcription, adopts a G-quadruplex structure. The sequence contains three
      binding elements for transcription factor Sp1, which is involved in the
      regulation of HIV-1 latency, reactivation, and high-level virus expression. We
      show that the three Sp1 binding motifs can adopt different forms of G-quadruplex
      structure and that the Sp1 protein can recognize and bind to its site folded into
      a G-quadruplex. In addition, a c-kit2 specific antibody, designated hf2, binds to
      two different G-quadruplexes formed in Sp1 sites. Since U3 is encoded at both
      viral genomic ends, the G-rich sequence is also present in the RNA genome. We
      demonstrate that the RNA sequence of U3 forms dimers with characteristics known
      for intermolecular G-quadruplexes. Together with previous reports showing G
      quadruplex dimers in the gag and cPPT regions, these results suggest that
      integrity of the two viral genomes is maintained through numerous intermolecular
      G-quadruplexes formed in different RNA genome locations. Reconstituted reverse
      transcription shows that the potassium-dependent structure formed in U3 RNA
      facilitates RT template switching, suggesting that the G-quadruplex contributes
      to recombination in U3.

PMID- 24735381
TI  - The effect of angiotensin-converting enzyme inhibitors on the rate of ascending
      aorta dilation in patients with bicuspid aortic valve.
AB  - BACKGROUND: Bicuspid aortic valve (BAV), the most common congenital heart defect,
      is associated with progressive aortic dilation and increased risk of dissection
      and rupture. The use of an angiotensin-converting enzyme (ACE) inhibitor has
      recently proven effective in slowing the rate of aortic dilation in other
      aortopathies, suggesting it may also be useful in managing BAV. We sought to
      determine whether ACE inhibitors effectively reduce the rate of aortic dilation
      in adolescents and young adults with BAV. METHODS: A retrospective cohort study
      was undertaken. Subjects receiving ACE inhibitor therapy were compared with
      controls with BAV and matched for the degree of aortic regurgitation. The rate of
      change in ascending aorta diameter was compared between the two groups. RESULTS:
      Among the 141 subjects identified in the patient records, 103 were receiving no
      medication and 38 were taking ACE inhibitors. Over a mean follow-up of 37 months,
      the ascending aorta Z-score increased slightly among those receiving ACE
      inhibitor +4.5 +/- 1.6 to +4.7 +/- 1.6. The rate of change was no different than
      those subjects not receiving ACE inhibitors, P = .64. CONCLUSION: In an
      adolescent and young adult population with an isolated BAV, there is no proven
      benefit to ACE inhibitor use with regard to slowing rate of ascending aortic
      dilation.

PMID- 24735382
TI  - Putative association between the -1415 T/C polymorphism of spermidine/spermine N1
      acetyltransferase (SSAT1) gene and alcohol use disorders in women and men.
AB  - BACKGROUND: The activity of N-methyl-D-aspartate (NMDA) glutamate receptor, which
      responds to the levels of polyamines, modifies the neurotoxicity caused by
      ethanol. We aimed to investigate if the functionality of the spermidine/spermine
      N1-acetyltransferase (SSAT1) gene could be associated with a differential risk
      for alcoholism. METHODS: We studied a sample of 586 subjects: 104 alcohol
      dependent patients, 273 patients with psychiatric disorders but without substance
      dependence, and 209 healthy controls. After gender stratification, the allele
      frequency distribution of the SSAT1 gene was compared between these three groups.
      RESULTS: In females, the TC genotype was significantly more frequent in alcohol
      dependent patients than in non-alcohol-dependent psychiatric controls (chi(2 )=
      7.509 df = 2, p = 0.023). A trend was found when alcohol-dependent females were
      compared with the healthy control group (chi(2 )= 4.897 df = 2, p = 0.086). No
      statistical differences were found among the males. DISCUSSION AND CONCLUSION:
      Gender differences in the regulation of SSAT1 gene expression may possibly be due
      to gender-specific effects of stress, ethanol toxicity, and/or polyamines levels.
      Further studies are needed to confirm our findings.

PMID- 24735383
TI  - Genotypes and phenotypes of congenital goitre and hypothyroidism caused by
      mutations in dual oxidase 2 genes.
AB  - OBJECTIVE: The aim of this study was to screen for DUOX2, TPO and TG mutations in
      Chinese patients with congenital hypothyroidism (CH) and goitre and to define the
      relationships between DUOX2 genotypes and clinical phenotypes. METHODS: Blood
      samples were collected from 67 patients with CH and goitre in Shandong Province,
      China. Genomic DNA was extracted from peripheral blood leucocytes. PCR and direct
      sequencing were used to analyse all exons of DUOX2, TPO and TG. Detailed medical
      records were then collected, and the relationship between DUOX2 genotype and the
      clinical phenotype of CH and goitre caused by DUOX2 mutations was investigated.
      RESULTS: Analysis of DUOX2 revealed nine mutations, including one novel nonsense
      mutation (p.W734X), six novel missense mutations (p.N100D, p.S660L, p.A1131S,
      p.W1181G, p.A1206T and p.R1267W) and two recurrent mutations (p.R701X and
      p.R1110Q) in 10 patients from 10 unrelated families. Monoallelic and compound
      heterozygous mutations in DUOX2 were associated with permanent or transient CH.
      No mutation was found after screening all exons of TPO and TG. CONCLUSION: Our
      study identified DUOX2 mutations in 14.9% of Chinese patients investigated with
      CH and goitre. Because the relationships between DUOX2 genotypes and clinical
      phenotypes are extremely complex, however, further studies are needed to identify
      more mutations in known genes which are involved in CH and goitre.

PMID- 24735384
TI  - Iridoid glycosides from Alonsoa meridionalis.
AB  - A new iridoid glucoside has been isolated from the Chilean native Alonsoa
      meridionalis (L.f.) Kuntze. Its structure has been assigned as 6'-O-beta-d
      glucopyranosyl-8-O-acetylharpagide (1) by using spectroscopic methods.
      Harpagoside (2), laterioside (3) and verbascoside (4) were also identified.

PMID- 24735386
TI  - Complementary modulation of N2 and CRN by conflict frequency.
AB  - The present study investigated the modulation of the N2 and the correct-related
      negativity (CRN) by conflict frequency. Conflict costs, as measured by reaction
      times and error rate, were reduced with increasing conflict frequency, indicating
      improved conflict resolution. N2 amplitudes in incompatible trials increased with
      higher conflict frequency, while postresponse CRN amplitudes decreased. In
      concert with behavioral findings of reduced conflict costs and greater
      interference suppression, the increase of N2 might reflect enhanced conflict
      resolution during stimulus processing. The CRN, however, might reflect
      postresponse implementation of cognitive control, which is reduced when conflict
      is already adequately resolved during stimulus processing. Furthermore, N2 and
      CRN in incompatible trials were inversely related on the between- and within
      subject level, implying that the two modes of implementing cognitive control are
      applied complementarily. 

PMID- 24735385
TI  - Safety evaluation of combination CCNU and continuous toceranib phosphate
      (Palladia((r)) ) in tumour-bearing dogs: a phase I dose-finding study.
AB  - While maintaining a standard toceranib dosage [2.75 mg kg(-1) , PO, every other
      day (EOD)], three dose-escalating CCNU cohorts up to and including 60 mg m(-2) ,
      PO, q3wk, were completed. The dose-limiting toxicities (DLT) for the combination
      were neutropenia and the maximum tolerated dose (MTD) for CCNU when given with
      continuous toceranib was determined to be 50 mg m(-2) , q3wk. While activity is
      not a primary objective of phase I trials, we observed one complete (lymphoma)
      and four partial responses (lymphoma, sarcoma, undifferentiated carcinoma and
      prostatic carcinoma) and two dogs experienced stable disease for >6 weeks
      [gastric adenocarcinoma and metastatic multilobulated osteochondrosarcoma (MLO)]
      for an objective response rate of 38.4% and a biological response rate of 53.8%.
      Concurrent continuous toceranib (2.75 mg kg(-1) , EOD) and pulse dose CCNU (50 mg
      m(-2) , q3wk) was well tolerated. Phase II effectiveness and phase III
      prospective randomized trials should further interrogate the potential activity
      of this combination. 

PMID- 24735387
TI  - Geometrically enforced donor-facilitated dehydrocoupling leading to an isolable
      arsanylidine-phosphorane.
AB  - A proximate Lewis basic group facilitates the mild dehydrogenative P-As
      intramolecular coupling in the phosphine-arsine peri-substituted acenaphthene 3,
      affording thermally and hydrolytically stable arsanylidine-phosphorane 4 with a
      sterically accessible two-coordinate arsenic atom. The formation of 4 is
      thermoneutral due to the dehydrogenation being concerted with the donor
      coordination. Reaction of 4 with a limited amount of oxygen reveals arsinidene
      like reactivity via formation of cyclooligoarsines, supporting the formulation of
      the bonding in 4 as base-stabilized arsinidene R3P->AsR. 

PMID- 24735388
TI  - Agreement between parents and adolescents on emotional and behavioral problems
      and its associated factors among Chinese school adolescents: a cross-sectional
      study.
AB  - BACKGROUND: Most studies about informant agreements on adolescents' emotional and
      behavioral problems have been conducted in Western countries, but this subject
      has not been well researched in China. The aim of this study was to evaluate the
      pattern of parent-adolescent agreement on adolescents' problems and its
      associated factors among school-age adolescents in China. METHODS: This cross
      sectional study was conducted in November and December of 2010. A questionnaire
      including the Child Behavior Checklist (CBCL), the Youth Self-Report (YSR), the
      Family Environment Scale (FES) and the characteristics of the child (age and
      gender), parents (parent-adolescent relationship and parental expectations) and
      family (family structure, negative life events) was distributed to our study
      population. A total of 2,199 Chinese adolescents (aged 11-18) from 15 public
      schools in Liaoning Province, who completed the questionnaire, became our final
      participants. Pearson's correlation coefficient was used to assess parent
      adolescent agreement, and linear regression analysis was used to explore the
      associated factors of parent-adolescent discrepancies on emotional and behavioral
      problems. RESULTS: The parent-adolescent agreement on emotional and behavioral
      problems was high (mean r = 0.6). The scores of YSR were higher than those of
      CBCL. Factors that increased informant discrepancies on emotional and behavioral
      problems were boys, older age, the experience of negative life events, low levels
      of cohesion and organization, and high levels of conflict in the family.
      CONCLUSIONS: A high level of parent-adolescent agreement on emotional and
      behavioral problems was found. Adolescents reported more problems than their
      parents did. Family environment is an important factor to be considered when
      interpreting informant discrepancies on the mental health of Chinese adolescents.

PMID- 24735389
TI  - The social acceptability of handheld umbrellas for sun protection.
AB  - PURPOSE: Little is known about handheld umbrella (HU) use for sun protection in
      the United States. We sought to determine whether women consider the HU a
      socially acceptable form of sun protection and whether viewing pictures of famous
      women carrying umbrellas is influential. METHODS: This is a cross-sectional
      survey study of 382 women. Participants viewed a collage of famous women carrying
      umbrellas to assess effect on social acceptability. RESULTS: Twelve percent had
      used a HU for sun protection. Participants were more likely to use an umbrella
      after viewing the collage (P<0.001). The majority would consider umbrella use if
      recommended by a dermatologist. Independent predictors of social acceptability
      were age, had not lived in another country, sun protective clothing use and no
      sunscreen use, while skin color, ethnicity and education were not. Mean rating of
      social acceptability was an intermediate score of 5.41 (1=not acceptable,
      10=totally acceptable) and increased to 5.88 postcollage (P<0.001). CONCLUSION:
      Social acceptability of HUs was moderate. Popular media may play a role in
      whether women view HUs as a socially acceptable form of sun protection.
      Dermatologists may consider recommending HUs as an adjunct but not replacement
      for other methods of sun protection.

PMID- 24735390
TI  - Carbon quantum dot/NiFe layered double-hydroxide composite as a highly efficient
      electrocatalyst for water oxidation.
AB  - The design of highly efficient, durable, and earth-abundant catalysts for the
      oxygen evolution reaction is crucial to a variety of important energy conversion
      and storage processes. Here, we use carbon quantum dots (CQDs, ~5 nm) to form
      hybrids with the ultrathin nickel-iron layered double-hydroxide (NiFe-LDH)
      nanoplates. The resulting CQD/NiFe-LDH complex exhibits high electrocatalytic
      activity (with an overpotential of ~235 mV in 1 M KOH at a current density of 10
      mA cm(-2)) and stability for oxygen evolution, which almost exceed the values of
      all previously reported Ni-Fe compounds and were comparable to those of the most
      active perovskite-based catalyst. 

PMID- 24735391
TI  - Is ureteral stent placement by the transurethral approach during robot-assisted
      radical prostatectomy an effective option to preoperative technique?
AB  - Ureteral stent placement may be needed in patients undergoing robot-assisted
      radical prostatectomy (RARP) in cases of a large median lobe or previous
      transurethral surgery to prevent damage to the ureteral orifices. Unpredictable
      anatomic variants or technical difficulties in bladder neck section may
      necessitate intraoperative stent placement. We describe our original, simple, and
      feasible transurethral stent placement technique during RARP, which could be a
      valid option to preoperative technique.

PMID- 24735394
TI  - Stereoselective transformations of (+)-abietic acid into (+)-vitedoin B and (+)
      negundoin A.
AB  - The first synthesis of spirolactone (+)-vitedoin B (14 steps, 8.0% global yield)
      and spiro enol ether (+)-negundoin A (19 steps, 3.7% global yield), via a nor
      labdane acetoxy ester, has been achieved starting from commercial (+)-abietic
      acid. 

PMID- 24735395
TI  - The Kv7 potassium channel activator retigabine decreases alcohol consumption in
      rats.
AB  - BACKGROUND: Activation of Kv7 potassium channels may decrease the reactivity of
      mesolimbic dopaminergic neurons that are implicated in mediating the reinforcing
      effects of ethanol. OBJECTIVES: The objective of this study was to determine
      whether the administration of the Kv7 potassium channel opener retigabine would
      decrease ethanol intake in Long Evans rats. METHODS: A limited access two-bottle
      choice model of alcohol (10% solution) consumption was used in this study. A
      separate group of animals was tested to evaluate the actions of retigabine on
      sucrose (5% solution) consumption to determine whether this drug might produce
      non-selective impairment of the ability of rats to drink liquids. Animals were
      treated with either vehicle or increasing doses (2.5-7.5 mg/kg SC) of retigabine
      administered over a 3-day period. RESULTS: Compared to vehicle, retigabine at a
      dose of 7.5 mg/kg produced a reduction in the amount of ethanol consumed. These
      effects did not occur in association with significant changes in water
      consumption. A significant time effect was found for the actions of retigabine in
      sucrose-drinking rats with a trend for an increase in sucrose intake with the
      highest dose of retigabine administered. CONCLUSIONS: These results indicate that
      the administration of retigabine may produce a decrease in ethanol consumption by
      rats at doses that do not significantly reduce the drinking of either water or a
      sucrose solution. These findings are consistent with the hypothesis that
      activation of Kv7 channels facilitates the reduction of alcohol consumption in
      the rat.

PMID- 24735396
TI  - Comparative thermodynamic analysis of zinc binding to the His/Cys motif in virion
      infectivity factor.
AB  - HIV-1 virion infectivity factor (Vif) is an accessory protein that induces the
      proteasomal degradation of the host restriction factor, apolipoprotein B mRNA
      editing enzyme catalytic polypeptide-like 3G (APOBEC3G). Degradation of APOBEC3G
      requires the interaction of Vif with Cul5, the scaffold for an E3 ubiquitin
      ligase. A highly conserved region in HIV-1 Vif termed the HCCH motif binds zinc
      and is critical for recruitment of Cul5 and degradation of APOBEC3G. To gain
      thermodynamic and mechanistic insight into zinc binding to diverse Vif proteins,
      we have employed a combination of isothermal titration calorimetry, analytical
      ultracentrifugation, and Cul5 pull down assays. The proton linkage of zinc
      binding to HIV-1 Vif was analyzed under different buffer conditions and
      consistent with the release of two Cys-thiol protons upon zinc binding,
      supporting earlier EXAFS studies. Zinc binding to Vif proteins from HIV-1,
      SIVAgm, HIV-2, and SIVMac followed a trend in which the enthalpy of zinc binding
      became less favorable and the entropy of zinc binding became more favorable.
      Using AUC, we determined that zinc induced oligomerization of Vif proteins from
      HIV-1 and SIVAgm but had little or no effect on the oligomeric properties of Vif
      proteins from HIV-2 and SIVMac. The zinc dependence of Cul5 recruitment by Vif
      was investigated. All Vif proteins except HIV-2 Vif required zinc to stabilize
      the interaction with Cul5. The trends in enthalpy-entropy compensation, zinc
      induced oligomerization, and Cul5 recruitment are discussed in terms of the apo
      conformation of the HCCH motif and the role of zinc in stabilizing the structure
      of Vif. 

PMID- 24735397
TI  - Predicting habitat distribution of five heteropteran pest species in Iran.
AB  - In agroecosystems, potential species distribution models are extensively applied
      in pest management strategies, revealing species ecological requirements and
      demonstrating relationships between species distribution and predictive
      variables. The Maximum Entropy model was used to predict the potential
      distribution of five heteropteran key pests in Iran, namely Adelphocoris
      lineolatus (Goeze) (Hemiptera: Miridae), Lygus pratensis (L.), Apodiphus amygdali
      (Germar) (Hemiptera: Pentatomidae), Nezara viridula (L.), and Nysius cymoides
      (Spinola) (Hemiptera: Lygaeidae). A total of 663 samples were collected from
      different parts of Iran. The altitude and climate variable data were included in
      the analysis. Based on test and training data, the area under the receiver
      operating characteristic curve values were above 0.80, the binomial omission test
      with the lowest presence threshold for all species was statistically significant
      (< 0.01), and the test omission rates were less than 3%. The suitability of areas
      in Iran for A. amygdale (Germar) (Hemiptera: Pentatomidae), N. cymoides (Spinola)
      (Hemiptera: Lygaeidae), A. lineolatus (Goeze) (Hemiptera: Miridae), L. pratensis
      (L.), and N. viridula (L.) (Hemiptera: Pentatomidae), ranked as 78.86%, 68.78%,
      43.29%, 20%, and 15.16%, respectively. In general, central parts of Iran
      including salt lakes, deserts, and sand dune areas with very high temperatures
      and windy weather were predicted to be less suitable, while other regions, mainly
      northern parts, were most suitable. These new data could be applied practically
      for the design of integrated pest management and crop development programs.

PMID- 24735398
TI  - Genomic and metabolic comparison with Dickeya dadantii 3937 reveals the emerging
      Dickeya solani potato pathogen to display distinctive metabolic activities and
      T5SS/T6SS-related toxin repertoire.
AB  - BACKGROUND: The pectinolytic enterobacteria of the Pectobacterium and Dickeya
      genera are causative agents of maceration-associated diseases affecting a wide
      variety of crops and ornamentals. For the past decade, the emergence of a novel
      species D. solani was observed in potato fields in Europe and the Mediterranean
      basin. The purpose of this study is to search by comparative genomics the genetic
      traits that could be distinctive to other Dickeya species and be involved in D.
      solani adaptation to the potato plant host. RESULTS: D. solani 3337 exhibits a
      4.9 Mb circular genome that is characterized by a low content in mobile elements
      with the identification of only two full length insertion sequences. A genomic
      comparison with the deeply-annotated model D. dadantii 3937 strain was performed.
      While a large majority of Dickeya virulence genes are shared by both strains, a
      few hundreds genes of D. solani 3337, mostly regrouped in 25 genomic regions, are
      distinctive to D. dadantii 3937. These genomic regions are present in the other
      available draft genomes of D. solani strains and interestingly some of them were
      not found in the sequenced genomes of the other Dickeya species. These genomic
      regions regroup metabolic genes and are often accompanied by genes involved in
      transport systems. A metabolic analysis correlated some metabolic genes with
      distinctive functional traits of both D. solani 3337 and D. dadantii 3937. Three
      identified D. solani genomic regions also regroup NRPS/PKS encoding genes. In
      addition, D. solani encodes a distinctive arsenal of T5SS and T6SS-related toxin
      antitoxin systems. These genes may contribute to bacteria-bacteria interactions
      and to the fitness of D. solani to the plant environment. CONCLUSIONS: This study
      highlights the genomic specific traits of the emerging pathogen D. solani and
      will provide the basis for studying those that are involved in the successful
      adaptation of this emerging pathogen to the potato plant host.

PMID- 24735399
TI  - The quiet revolution in Asia's rice value chains.
AB  - There is a rapid transformation afoot in the rice value chain in Asia. The
      upstream is changing quickly-farmers are undertaking capital-led intensification
      and participating in burgeoning markets for land rental, fertilizer and
      pesticides, irrigation water, and seed, and shifting from subsistence to small
      commercialized farms; in some areas landholdings are concentrating. Midstream, in
      wholesale and milling, there is a quiet revolution underway, with thousands of
      entrepreneurs investing in equipment, increasing scale, diversifying into higher
      quality, and the segments are undergoing consolidation and vertical coordination
      and integration. Mills, especially in China, are packaging and branding, and
      building agent networks in wholesale markets, and large mills are building direct
      relationships with supermarkets. The downstream retail segment is undergoing a
      "supermarket revolution," again with the lead in change in China. In most cases
      the government is not playing a direct role in the market, but enabling this
      transformation through infrastructural investment. The transformation appears to
      be improving food security for cities by reducing margins, offering lower
      consumer rice prices, and increasing quality and diversity of rice. This paper
      discusses findings derived from unique stacked surveys of all value chain
      segments in seven zones, more and less developed, around Bangladesh, China,
      India, and Vietnam. 

PMID- 24735400
TI  - Subcutaneous pulsatile glucocorticoid replacement therapy.
AB  - The glucocorticoid hormone cortisol is released in pulses resulting in a complex
      and dynamic ultradian rhythm of plasma cortisol that underlies the classical
      circadian rhythm. These oscillating levels are also seen at the level of tissues
      such as the brain and trigger pulses of gene activation and downstream
      signalling. Different patterns of glucocorticoid presentation (constant vs
      pulsatile) result not only in different patterns of gene regulation but also in
      different neuroendocrine and behavioural responses. Current 'optimal'
      glucocorticoid replacement therapy results in smooth hormone blood levels and
      does not replicate physiological pulsatile cortisol secretion. Validation of a
      novel portable pulsatile continuous subcutaneous delivery system in healthy
      volunteers under dexamethasone and metyrapone suppression. Pulsatile subcutaneous
      hydrocortisone more closely replicates physiological circadian and ultradian
      rhythmicity. 

PMID- 24735401
TI  - Establishment and characterization of immortalized bovine endometrial epithelial
      cells.
AB  - Bovine primary uterine endometrial epithelial cells (EECs) are not ideal for long
      term studies, because primary EECs lose hormone responsiveness quickly, and/or
      they tend to have a short life span. The aims of this study were to establish
      immortalized bovine EECs and to characterize these cells following long-term
      cultures. Immortalized bovine EECs were established by transfecting retroviral
      vectors encoding human papillomavirus (HPV) E6 and E7, and human telomerase
      reverse transcriptase (hTERT) genes. Established bovine immortalized EECs
      (imEECs) showed the same morphology as primary EECs, and could be grown without
      any apparent changes for over 60 passages. In addition, imEECs have maintained
      the features as EECs, exhibiting oxytocin (OT) and interferon tau (IFNT)
      responsiveness. Therefore, these imEECs, even after numbers of passages, could be
      used as an in vitro model to investigate cellular and molecular mechanisms, by
      which the uterine epithelium responds to IFNT stimulation, the event required for
      the maternal recognition of pregnancy in the bovine species. 

PMID- 24735402
TI  - A new naphthalene glycoside from the sponge-derived fungus Arthrinium sp. ZSDS1
      F3.
AB  - One new naphthalene derivative, 1,8-dihydroxynaphthol-1-O-alpha-l
      rhamnopyranoside (1), together with one known alpha-dibenzopyrone, alternariol
      (2), and five xanthones (3-7) were isolated from the sponge-derived fungus
      Arthrinium sp. ZSDS1-F3. All the isolated compounds (1-7) were established by
      comprehensive analysis of the spectral data, especially 1D and 2D NMR (HMQC and
      HMBC) spectra. In the primary bioassays, compound 3 exhibited moderate COX-2
      inhibition, with IC50 values of 12.2 MUM. 

PMID- 24735403
TI  - Mechanism of singlet fission in thin films of 1,3-diphenylisobenzofuran.
AB  - In order to elucidate the mechanism of singlet fission in thin films of 1,3
      diphenylisobenzofuran (1) we have performed ultrafast transient absorption
      spectroscopy as a function of sample temperature and excitation fluence on
      polycrystalline thin films composed of two polymorphs. Our earlier investigations
      revealed that films enriched in a particular polymorph of 1 displayed near 200%
      efficiency for triplet formation at 77 K, while films composed primarily of a
      second polymorph had a very low triplet quantum yield. Present data confirm the
      triplet yield disparities in the two polymorphs and demonstrate the distinct
      fates of the initially prepared singlets in films of different structure. Singlet
      fission is inhibited in the more stable polymorph due to rapid excimer formation
      and trapping. The less stable polymorph undergoes highly efficient singlet
      fission with a dominant time constant of 10-30 ps and without strong thermal
      activation. Transient absorption measurements with varying excitation fluence
      indicate that singlet-singlet annihilation is a primary competitor of singlet
      fission at higher fluence and that fission from higher-lying states can also
      contribute to the triplet formation process. Measurements employing different
      excitation energies and sample temperatures reveal the role that trapping
      processes play in attenuating the triplet quantum yield to produce the complex
      temperature dependence of the singlet fission yield. The rate constants for
      singlet fission itself are essentially temperature independent. 

PMID- 24735404
TI  - A novel doxorubicin-loaded in situ forming gel based high concentration of
      phospholipid for intratumoral drug delivery.
AB  - The purpose of this study was to develop a safe and effective drug delivery
      system for local chemotherapy. A novel injectable in-situ-forming gel system was
      prepared using small molecule materials, including phospholipids, medium chain
      triglycerides (MCTs), and ethanol. Thus, this new sustained release system was
      named PME (first letter of phospholipids, MCT, and ethanol). PME has a well
      defined molecule structure, a high degree of safety, and better biocompatible
      characteristics. It was in sol state with low viscosity in vitro and turned into
      a solid or semisolid gel in situ after injection. When loaded with doxorubicin
      (Dox), PME-D (doxorubicin-loaded PME) exhibited notably antitumor efficiency in
      S180 sarcoma tumors bearing mice after a single intratumoral injection. In vitro,
      PME-D had remarkable antiproliferative efficacies against MCF-7 breast cancer
      cells for over 5 days. Moreover, the initial burst effect can hardly be observed
      from PME system, which was different from many other in-situ-forming gels. The in
      vivo biodistribution study showed the high Dox concentration in tumors compared
      with other major organs after PME-D intratumoral administration. The strong
      signal in tumors was retained for more than 14 days after one single injection.
      The high concentration of Dox in tumor and long-term retention may explain the
      superior therapeutic efficacy and reduced side effects. The PME-D in-situ-forming
      gel system is a promising drug delivery system for local chemotherapy. 

PMID- 24735405
TI  - From gut inflammation to gastrointestinal disorders current update on
      pathophysiology, molecular mechanism and pharmacological treatment modalities.

PMID- 24735406
TI  - Use of visual CO2 feedback as a retrofit solution for improving classroom air
      quality.
AB  - Carbon dioxide (CO2 ) sensors that provide a visual indication were installed in
      classrooms during normal school operation. During 2-week periods, teachers and
      students were instructed to open the windows in response to the visual CO2
      feedback in 1 week and open them, as they would normally do, without visual
      feedback, in the other week. In the heating season, two pairs of classrooms were
      monitored, one pair naturally and the other pair mechanically ventilated. In the
      cooling season, two pairs of naturally ventilated classrooms were monitored, one
      pair with split cooling in operation and the other pair with no cooling.
      Classrooms were matched by grade. Providing visual CO2 feedback reduced CO2
      levels, as more windows were opened in this condition. This increased energy use
      for heating and reduced the cooling requirement in summertime. Split cooling
      reduced the frequency of window opening only when no visual CO2 feedback was
      present. 

PMID- 24735407
TI  - Sense of coherence among cognitively intact nursing home residents--a five-year
      longitudinal study.
AB  - AIM AND OBJECTIVES: To examine how stable the sense of coherence (SOC) is over a
      five-year period among residents of nursing homes (NH) who are not cognitively
      impaired and whether components of social support influence SOC. BACKGROUND: Many
      studies have investigated the stability of SOC, and the findings have been
      inconsistent. Social support is a crucial resource in developing SOC. Few
      researchers have studied the stability of SOC and how various social support
      dimensions influence changes in SOC among older NH residents who are cognitively
      intact. DESIGN: The study was prospective and included baseline assessment and
      five-year follow-up. METHODS: The sample comprised 52 cognitively intact NH
      residents (Clinical Dementia Rating score <=0.5). We obtained data through direct
      interviews using the Social Provisions Scale and Sense of Coherence Scale.
      RESULTS: SOC increased statistically significantly from baseline to follow-up.
      The social support subdimension reassurance of worth predicted change in SOC
      after adjustment for sociodemographic factors. When controlled for baseline SOC,
      attachment was associated with change in SOC, but reassurance of worth was not.
      CONCLUSIONS: The study indicates that the change in SOC over time during the 5
      years of follow-up and the social support dimension attachment appear to be
      important components of change in SOC. Nursing personnel should be aware of the
      residents' individual needs for attachment and the importance of emotional
      support for personal strength and ability to cope.

PMID- 24735409
TI  - Hydrazide functionalized core-shell magnetic nanocomposites for highly specific
      enrichment of N-glycopeptides.
AB  - In view of the biological significance of glycosylation for human health,
      profiling of glycoproteome from complex biological samples is highly inclined
      toward the discovery of disease biomarkers and clinical diagnosis. Nevertheless,
      because of the existence of glycopeptides at relatively low abundances compared
      with nonglycosylated peptides and glycan microheterogeneity, glycopeptides need
      to be highly selectively enriched from complex biological samples for mass
      spectrometry analysis. Herein, a new type of hydrazide functionalized core-shell
      magnetic nanocomposite has been synthesized for highly specific enrichment of N
      glycopeptides. The nanocomposites with both the magnetic core and the polymer
      shell hanging high density of hydrazide groups were prepared by first
      functionalization of the magnetic core with polymethacrylic acid by reflux
      precipitation polymerization to obtain the Fe3O4@poly(methacrylic acid)
      (Fe3O4@PMAA) and then modification of the surface of Fe3O4@PMAA with adipic acid
      dihydrazide (ADH) to obtain Fe3O4@poly(methacrylic hydrazide) (Fe3O4@PMAH). The
      abundant hydrazide groups toward highly specific enrichment of glycopeptides and
      the magnetic core make it suitable for large-scale, high-throughput, and
      automated sample processing. In addition, the hydrophilic polymer surface can
      provide low nonspecific adsorption of other peptides. Compared to commercially
      available hydrazide resin, Fe3O4@PMAH improved more than 5 times the signal-to
      noise ratio of standard glycopeptides. Finally, this nanocomposite was applied in
      the profiling of N-glycoproteome from the colorectal cancer patient serum. In
      total, 175 unique glycopeptides and 181 glycosylation sites corresponding to 63
      unique glycoproteins were identified in three repeated experiments, with the
      specificities of the enriched glycopeptides and corresponding glycoproteins of
      69.6% and 80.9%, respectively. Because of all these attractive features, we
      believe that this novel hydrazide functionalized core-shell magnetic
      nanocomposite will shed new light on the profiling of N-glycoproteome from
      complex biological samples in high throughput. 

PMID- 24735408
TI  - Effects of dimethyl dicarbonate (DMDC) on the fermentation of litchi juice by
      Lactobacillus casei as an alternative of heat treatment.
AB  - This study investigated the effects of dimethyl dicarbonate (DMDC) on the
      fermentation of litchi juice by Lactobacillus casei as an alternative of heat
      treatment that may have undesirable effect on the juice. Quality attributes and
      products stability of both the fermented heat- and DMDC-treated litchi juice by
      L. casei were compared. It was found that residual indigenous microorganisms in
      both the heat- and DMDC-treated litchi juice cannot grow into dominant bacteria
      during further fermentation of litchi juice by L. casei. Compared with fermented
      heat-treated litchi juice, fermented DMDC-treated litchi juice showed a better
      color, flavor, and overall acceptance, and also retained more total phenolics and
      antioxidant capacity. The viability counts of L. casei in both the heat- and DMDC
      treated litchi juice were more 8.0 lg CFU/mL after 4 wk of storage at 4  degrees
      C. Also, some quality attributes in both the fermented heat- and DMDC-treated
      litchi juices, including pH, total phenolics, ascorbic acid, antioxidant
      capacity, and so on, showed the tendency to slow decrease during storage at 4 
      degrees C, but the scores of overall acceptance showed no reduction after the
      storage of 4 wk at 4  degrees C. On the whole, the application of DMDC treatment
      could be an ideal alternative of heat treatment to ensure the microbial safety,
      consistent sensory, and nutritional quality of fermented litchi juice prior to
      fermentation. PRACTICAL APPLICATION: The pasteurization treatment is often
      recommended prior to fermentation of fruit juice by probiotics, as it would lead
      to a rapid inactivation and inhibition of spoilage and pathogenic bacteria, and
      ensure the fermented products with consistent sensory and nutritional quality.
      Dimethyl dicarbonate (DMDC) is a powerful antimicrobial agent, which was approved
      for use as a microbial control agent in juice beverages by FDA. This study
      provides a scientific basis for the application of DMDC prior to fermentation of
      litchi juice.

PMID- 24735410
TI  - Egg and time limitation mediate an egg protection strategy.
AB  - The number of mature eggs remaining in the ovaries and the time left for
      oviposition determine the reproductive decisions of the hyperdiverse guild of
      insects that require discrete and potentially limiting resources for oviposition
      (such as seeds, fruits or other insects). A female may run out of eggs before all
      available oviposition sites are used (egg limitation), or die before using all of
      her eggs (time limitation). Females are predicted to change clutch size depending
      on whether eggs or time is the limiting resource. We extend this framework and
      ask whether the same constraints influence a strategy in which females modify
      eggs into protective shields. In response to egg parasitism cues, female seed
      beetles (Mimosestes amicus) lay eggs in vertical groups of 2-4, modifying the top
      1-3 eggs into shields in order to protect the bottom egg from attack by
      parasitoids. We made contrasting predictions of how egg and time limitation would
      influence egg size and the incidence and level of egg protection. By varying
      access to seed pods, we manipulated the number of remaining eggs a female had at
      the time she received a parasitism cue. Although egg size was not affected, our
      results confirm that egg-limited females protected fewer eggs and time-limited
      females protected more eggs. Female body size explained the number of eggs in a
      stack rather than host deprivation or the timing of parasitoid exposure. Our
      results clearly show that host availability relative to female age influences the
      incidence of egg protection in M. amicus. Furthermore, our study represents a
      novel use of life history theory to explain patterns in an unusual but compelling
      defensive behaviour. 

PMID- 24735411
TI  - Detection of central white matter injury underlying vestibulopathy after mild
      traumatic brain injury.
AB  - PURPOSE: To determine if central axonal injury underlies vestibulopathy and
      ocular convergence insufficiency after mild traumatic brain injury (TBI) by using
      tract-based spatial statistics (TBSS) analysis of diffusion-tensor imaging (DTI).
      MATERIALS AND METHODS: The institutional review board approved this study, and
      the requirement to obtain informed consent was waived. Diffusion-tensor images
      were retrospectively reviewed in 30 patients with mild TBI and vestibular
      symptoms and 25 patients with mild TBI and ocular convergence insufficiency.
      Control subjects consisted of 39 patients with mild TBI without vestibular
      abnormalities and 17 patients with mild TBI and normal ocular convergence.
      Fractional anisotropy (FA) maps were generated as a measure of white matter
      integrity and were analyzed with TBSS regression analysis by using a general
      linear model. DTI abnormalities were correlated with symptom severity,
      neurocognitive test scores, and time to recovery with the Pearson correlation
      coefficient. RESULTS: Compared with control subjects, patients with mild TBI and
      vestibular symptoms had decreased neurocognitive test scores (P < .05) and FA
      values in the cerebellum and fusiform gyri (P < .05). Patients with ocular
      convergence insufficiency had diminished neurocognitive test scores (P < .05) and
      FA values in the right anterior thalamic radiation and right geniculate nucleus
      optic tracts (P < .0001). Cerebellar injury showed an inverse correlation with
      recovery time (R = -0.410, P = .02). Anterior thalamic radiation injury showed
      correlation with decreased processing speed (R = 0.402, P < .05). CONCLUSION: DTI
      findings in patients with mild TBI and vestibulopathy support the hypothesis that
      posttraumatic vestibulopathy has a central axonal injury component. Peripheral
      vestibular structures were not assessed, and a superimposed peripheral
      contribution may exist. DTI evaluation of central vestibular structures may
      provide a diagnostic imaging tool in these patients and a quantitative biomarker
      to aid in prognosis.

PMID- 24735412
TI  - Surgical treatment of mammary carcinomas in dogs with or without postoperative
      chemotherapy.
AB  - This retrospective study identified prognostic factors associated with survival;
      and compared survival data in 94 canine mammary carcinoma (MCA) dogs treated with
      surgery (n = 58), or surgery and adjunct chemotherapy (n = 36), and a subset of
      dogs with poor prognostic factors. On multivariate analysis independent
      predictors of median survival time (MST) were clinical stage, lymphatic invasion
      (LI; present 179 days; none 1098 days), ulceration (present 118 days; none 443
      days) and surgical margins (incomplete 70 days; complete 872 days). Complete
      surgical margins were associated with MST in dogs with stages 1-3 MCA (incomplete
      68 days; complete 1098 days) and dogs with LI (incomplete 70 days; complete 347
      days). There was no statistically significant improvement in MST in dogs with
      advanced disease (stage 4 or LI) treated with adjunctive chemotherapy
      (chemotherapy 228 days; none 194 days); although five dogs with complete surgical
      margins that received mitoxantrone and carboplatin had a mean survival of 1139
      days. 

PMID- 24735414
TI  - Impaired neurovascular unit function contributes to persistent symptoms after
      concussion: a pilot study.
AB  - Research shows that approximately 14% of school age children with mild traumatic
      brain injury (TBI) including sports-related concussions (SRCs) remain symptomatic
      three months after injury. Advanced imaging studies early after injury have shown
      evidence of axonal damage, reduced N-acetyl aspartate (NAA) and impaired cerebral
      blood flow (CBF) in individuals with mild TBI. This study was undertaken to
      determine whether these techniques can provide valuable information in pediatric
      SRC patients with persistent post-concussive symptoms. Fifteen pediatric subjects
      ages 8 to 17 years with persistent post-concussive symptoms were evaluated using
      perfusion-weighted imaging (PWI), three-dimensional (3D) magnetic resonance
      spectroscopic imaging, and diffusion tensor imaging (DTI) three to 12 months post
      SRC. Data were compared with 15 demographically similar (age, gender, and body
      mass index) controls. In the bilateral thalami, SRC patients showed reduced CBF
      (p=0.02 and p=0.02) and relative cerebral blood volume (CBV; p=0.05 and p=0.03),
      compared with controls. NAA/creatine (Cr) and NAA/choline (Cho) ratios were
      reduced in the corpus callosum (p=0.003; p=0.05) and parietal white matter
      (p<0.001; p=0.006) of SRC subjects, compared with controls. Significant
      differences in DTI metrics differentiated patients with cognitive symptoms,
      compared with those without cognitive symptoms and controls. Advanced imaging
      methods detect a spectrum of injury including impaired axonal function, neuronal
      metabolism and perfusion, suggesting involvement of the neurovascular unit in the
      presence of persistent symptoms in pediatric SRC patients.

PMID- 24735413
TI  - ngs.plot: Quick mining and visualization of next-generation sequencing data by
      integrating genomic databases.
AB  - BACKGROUND: Understanding the relationship between the millions of functional DNA
      elements and their protein regulators, and how they work in conjunction to
      manifest diverse phenotypes, is key to advancing our understanding of the
      mammalian genome. Next-generation sequencing technology is now used widely to
      probe these protein-DNA interactions and to profile gene expression at a genome
      wide scale. As the cost of DNA sequencing continues to fall, the interpretation
      of the ever increasing amount of data generated represents a considerable
      challenge. RESULTS: We have developed ngs.plot - a standalone program to
      visualize enrichment patterns of DNA-interacting proteins at functionally
      important regions based on next-generation sequencing data. We demonstrate that
      ngs.plot is not only efficient but also scalable. We use a few examples to
      demonstrate that ngs.plot is easy to use and yet very powerful to generate
      figures that are publication ready. CONCLUSIONS: We conclude that ngs.plot is a
      useful tool to help fill the gap between massive datasets and genomic information
      in this era of big sequencing data.

PMID- 24735415
TI  - Does stress mediate the development of substance use disorders among youth
      transitioning to young adulthood?
AB  - BACKGROUND: Stress is a well-documented factor in the development of addiction.
      However, no longitudinal studies to date have assessed the role of stress in
      mediating the development of substance use disorders (SUD). Our previous results
      have demonstrated that a measure called Transmissible Liability Index (TLI)
      assessed during pre-adolescent years serves as a significant predictor of risk
      for substance use disorder among young adults. However, it remains unclear
      whether life stress mediates the relationship between TLI and SUD, or whether
      stress predicts SUD. METHODS: We conducted a longitudinal study involving 191
      male subjects to assess whether life stress mediates the relationship between TLI
      as assessed at age 10-12 and subsequent development of SUD at age 22, after
      controlling for other relevant factors. RESULTS: Logistic regression demonstrated
      that the development of SUD at age 22 was associated with stress at age 19. A
      path analysis demonstrated that stress at age 19 significantly predicted SUD at
      age 22. However, stress did not mediate the relationship between the TLI assessed
      at age 10-12 and SUD in young adulthood. CONCLUSIONS AND SCIENTIFIC SIGNIFICANCE:
      These findings confirm that stress plays a role in the development of SUD, but
      also shows that stress does not mediate the development of SUD. Further studies
      are warranted to clarify the role of stress in the etiology of SUD.

PMID- 24735416
TI  - The evolution of CT diagnosed papillae tip microcalcifications: can we predict
      the development of stones?
AB  - OBJECTIVES: To determine the incidence of computed tomography (CT) identifiable
      Randall plaques in a CT explored population; to determine the clinical relevance
      of this radiological finding by a 7-year follow-up; to determine a cut point to
      identify a population with high risk of developing calcium stone disease (SD).
      MATERIALS AND METHODS: Retrospective study of all patients explored by abdominal
      CT in our center between January and March 2005. INCLUSION CRITERIA: age 30-60
      years and no SD. Papillae attenuation was measured on nonenhanced CT in
      Hounsfield units (HU) and the mean of all papillae was calculated. Patients were
      re-evaluated after 7 years to identify calcium stone formers. Anamnesis and
      already available CT, ultrasound, kidney, ureter, and bladder radiograph (KUB) or
      intravenous urography (IVU) images performed as part of their follow-up were
      used. In patients with no follow-up, ultrasound and KUB were to be performed.
      Pearson correlation, Student t-test, and the receiver operator curve were used
      for statistical analysis. RESULTS: A total of 362 patients fulfilled the
      inclusion criteria and were analyzed; 12 developed calcium SD after 7 years. A
      significant difference was encountered between the papillae attenuation of stone
      formers (SF) versus non-SF (47.2HU vs. 35.5HU, p=0.001). There was good
      correlation between papillae attenuation and the possibility of developing SD
      (R=0.87). An optimal cut point of 43HU with a sensitivity of 81% and specificity
      of 97%, area under the curve 0.91, separated SF and non-SF. CONCLUSION: Patients
      with high papillae density have a higher risk of developing SD. A cut point of
      43HU could accurately be used to identify a high-risk population.

PMID- 24735418
TI  - Mesoscale effects in electrochemical conversion: coupling of chemistry to atomic-
      and nanoscale structure in iron-based electrodes.
AB  - The complex coupling of atomic, chemical, and electronic transformations across
      multiple length scales underlies the performance of electrochemical energy
      storage devices. Here, the coupling of chemistry with atomic- and nanoscale
      structure in iron conversion electrodes is resolved by combining pair
      distribution function (PDF) and small-angle X-ray scattering (SAXS) analysis for
      a series of Fe fluorides, oxyfluorides, and oxides. The data show that the anion
      chemistry of the initial electrode influences the abundance of atomic defects in
      the Fe atomic lattice. This, in turn, is linked to different atom mobilities and
      propensity for particle growth. Competitive nanoparticle growth in mixed anion
      systems contributes to a distinct nanostructure, without the interconnected
      metallic nanoparticles formed for single anion systems. 

PMID- 24735417
TI  - Vestibular disorders in euthyroid patients with Hashimoto's thyroiditis: role of
      thyroid autoimmunity.
AB  - INTRODUCTION: A relationship between vestibular disorders and thyroid
      autoimmunity independently from thyroid function has been postulated. AIM: To
      shed more light on the actual relationship between vestibular lesions and
      Hashimoto's thyroiditis (HT) regardless of thyroid function. METHODS: Forty-seven
      patients with HT (89.4% F; aged 48.3 +/- 12.7 years), 21 with multinodular goitre
      (MNG; 57.1% F; 54.1 +/- 9.8 years) and 30 healthy volunteers (56.7% F; 50.7 +/-
      13.9 years) were enrolled. Inclusion criteria were the presence of normal thyroid
      function tests and no clinical history of vestibular dysfunction. Each subject
      was submitted to complete vestibular evaluation [Caloric Test, Vestibular evoked
      myogenic potentials (VEMPs), Head Shaking Test (HST)]. RESULTS: 52.2% of HT
      patients showed an alteration of VEMPs and 44.7% of caloric test (P < 0.0001 for
      both). None of the MNG patients showed any vestibular alteration, while one
      healthy control showed an altered caloric test. A correlation was found between
      vestibular alterations of HT patients and the degree of serum TPOAb level, not
      affected by age and serum TSH value. By logistic regression analysis, the absence
      of thyroid autoimmunity significantly reduced the risk of vestibular alterations:
      HR 0.19 (95%CI: 0.003-0.25, P = 0.0004) for caloric test; HR 0.07 (95%CI: 0.02
      0.425, P < 0.0001) for VEMPs; and HR 0.22 (95%CI: 0.06-0.7, P = 0.01) for HST.
      CONCLUSION: In euthyroid HT patients, a significant relationship between
      subclinical vestibular damage and the degree of TPOAb titre was documented. This
      finding suggests that circulating antithyroid autoantibodies may represent a risk
      factor for developing vestibular dysfunction. An accurate vestibular evaluation
      of HT patients with or without symptoms is therefore warranted.

PMID- 24735419
TI  - Translational research investigations on ATP7A: an important human copper ATPase.
AB  - In more than 40 years since copper deficiency was delineated in pediatric
      subjects with Menkes disease, remarkable advances in our understanding of the
      clinical, biochemical, and molecular aspects of the human copper transporter
      ATP7A have emerged. Mutations in the gene encoding this multitasking molecule are
      now implicated in at least two other distinctive phenotypes: occipital horn
      syndrome and ATP7A-related isolated distal motor neuropathy. Several other novel
      inherited disorders of copper metabolism have been identified in the past several
      years, aided by advances in human gene mapping and automated DNA sequencing. In
      this paper, I review the history and evolution of our understanding of disorders
      caused by impaired ATP7A function, and outline future challenges. 

PMID- 24735420
TI  - Internet-based individually versus group guided self-help treatment for social
      anxiety disorder: protocol of a randomized controlled trial.
AB  - BACKGROUND: Social anxiety disorder (SAD) is one of the most common mental
      disorders and causes subjective suffering and economic burden worldwide. Although
      effective treatments are available, a lot of cases go untreated. Internet-based
      self-help is a low-threshold and flexible treatment alternative for SAD. Various
      studies have already shown that internet-based self-help can be effective to
      reduce social phobic symptoms significantly. Most of the interventions tested
      include therapist support, whereas the role of peer support within internet-based
      self-help has not yet been fully understood. There is evidence suggesting that
      patients' mutual exchange via integrated discussion forums can increase the
      efficacy of internet-based treatments. This study aims at investigating the added
      value of therapist-guided group support on the treatment outcome of internet
      based self-help for SAD. METHODS/DESIGN: The study is conducted as a randomized
      controlled trial. A total of 150 adults with a diagnosis of SAD are randomly
      assigned to either a waiting-list control group or one of the active conditions.
      The participants in the two active conditions use the same internet-based self
      help program, either with individual support by a psychologist or therapist
      guided group support. In the group guided condition, participants can communicate
      with each other via an integrated, protected discussion forum. Subjects are
      recruited via topic related websites and links; diagnostic status will be
      assessed with a telephone interview. The primary outcome variables are symptoms
      of SAD and diagnostic status after the intervention. Secondary endpoints are
      general symptomology, depression, quality of life, as well as the primary outcome
      variables 6 months later. Furthermore, process variables such as group processes,
      the change in symptoms and working alliance will be studied. DISCUSSION: The
      results of this study should indicate whether group-guided support could enhance
      the efficacy of an internet-based self-help treatment for SAD. This novel
      treatment format, if shown effective, could represent a cost-effective option and
      could further be modified to treat other conditions, as well. TRIAL REGISTRATION:
      ISRCTN75894275.

PMID- 24735421
TI  - The bioaccumulation and physiological effects of heavy metals in carrots, onions,
      and potatoes and dietary implications for Cr and Ni: a review.
AB  - The bioaccumulation of heavy metals in food tubers (carrots, onions, and
      potatoes) as a result of polluted irrigation water has been studied in this
      review paper. Given that heavy metals can cause a considerable oxidative stress,
      the impact of these metals to the physiology of the plants has also been
      assessed. The consumption of vegetables cross-contaminated with heavy metals
      carries a considerable risk for humans (especially for children and pregnant
      women) and these dietary implications are discussed while European Food Safety
      Authority has been urged to look into this matter of concern. 

PMID- 24735422
TI  - Hepatic-targeted gene delivery using cationic mannan vehicle.
AB  - The incidence of hepatic diseases continuously increases worldwide and causes
      significant mortality because of inefficient pharmacotherapy. Gene therapy is a
      new strategy in the treatment of hepatic diseases, but the disadvantages of
      insufficient retention in the liver and undesirable side effects hinder its
      application. In this study, we developed a novel nonviral vehicle targeted to
      liver. Mannan was cationized with spermine at varying grafted ratios to deliver
      the gene and was optimized in cytotoxicity and transfection in vitro. A spermine
      mannan (SM)-based delivery system was proven to be hepatic targeted and was
      capable of prolonging the gene retention period in the liver. Moreover, SM at N/P
      of 20 was confirmed to be less interfered with by the serum. Optimized SM vehicle
      has relatively high hepatic transfection with almost no toxicity induction in the
      liver, which highlighted its potential in the treatment of hepatic diseases. 

PMID- 24735423
TI  - Thyroid status and renal function in older persons in the general population.
AB  - BACKGROUND: Prevalence estimates of thyroid dysfunction and chronic kidney
      disease both increase with age. The aim of this study was to investigate the
      cross-sectional association between low thyroid function and renal function in
      subjects aged 85 years and to assess whether a low thyroid function at age 85
      years is associated with an accelerated decline in renal function during follow
      up. METHODS: We included 558 participants from the Leiden 85-plus Study. At
      baseline (age 85 y), TSH, free T4 (fT4), and free T3 levels were measured.
      Thyroid function groups were created using clinical cutoff values of TSH and fT4.
      Serum creatinine concentrations were determined at baseline and annually during a
      5-year follow-up period. Estimated glomerular filtration rates (eGFRs) were
      calculated by means of the Modification of Diet in Renal Disease Study equation.
      RESULTS: At baseline, subjects with higher levels of TSH and lower levels of fT4
      and free T3 had lower renal function. Participants with hypothyroidism [mean 53.7
      (2.0) mL/min per 1.73 m(2))] and subclinical hypothyroidism [55.7 (2.1) mL/min
      per 1.73 m(2)] had lower mean eGFRs (SE) than participants with normal thyroid
      function [59.5 (0.7) mL/min per 1.73 m(2)]; the highest eGFR was observed in
      participants with hyperthyroidism [eGFR 61.5 (3.1) mL/min per 1.73 m(2)] (P for
      trend = .004). There was no association between thyroid hormone levels at
      baseline and the change in renal function during follow-up. CONCLUSIONS: Although
      low thyroid function was associated with lower renal function at age 85 years, an
      association between a low thyroid function and change in renal function over time
      was absent. Our findings question the causal relevance of the thyroid status for
      the deterioration of renal function in the oldest old.

PMID- 24735424
TI  - Bacterial DNA translocation holds increased insulin resistance and systemic
      inflammatory levels in morbid obese patients.
AB  - BACKGROUND: Morbidly obese patients show several common comorbidities associated
      with immunological alterations such as a sustained low-level proinflammatory
      profile. Bacterial product translocation is frequent in inflammation-related
      diseases and may aggravate patients' clinical outcome. DESIGN: Consecutively
      admitted morbidly obese patients who presented indications for bariatric surgery
      were studied. Before surgery, patients were subjected to a modified fasting diet.
      Patients underwent surgery by sleeve gastrectomy or laparoscopic Roux-en-Y
      gastric bypass. Clinical and analytical parameters were recorded. Blood samples
      were collected at baseline, at the end of a 3-month modified fasting period, and
      3, 6, and 12 months after surgery. Serum cytokine and endotoxin levels were
      evaluated by flow cytometry and ELISA, respectively. Bacterial DNA was identified
      in blood by broad-range PCR of prokaryote 16SrRNA gene and partial sequencing
      analysis. RESULTS: Fifty-eight patients were included in the study. All patients
      showed a significantly reduced weight and body mass index at each time-point.
      Postoperative mortality was null. Bacterial DNA translocation rate was 32.8% (19
      of 58) at baseline; 13.8% (8 of 58) after the modified fasting period; and 13.8%
      (8 of 58), 1.8% (1 of 58), and 5.2% (3 of 58) at 3, 6, and 12 months after
      surgery. Proinflammatory cytokines, serum endotoxin levels, and insulin
      resistance remained increased in patients with bacterial DNA despite weight loss
      and were individually affected by the appearance/clearance of bacterial DNA in
      blood. Multivariate analyses revealed bacterial DNA as an independent significant
      factor, explaining the systemic cytokine response and the insulin resistance
      levels in the studied population. CONCLUSION: Bacterial DNA translocation holds
      increased insulin resistance and systemic inflammatory levels in morbidly obese
      patients despite significant weight loss.

PMID- 24735425
TI  - beta-cell telomere attrition in diabetes: inverse correlation between HbA1c and
      telomere length.
AB  - CONTEXT: Although accelerated beta-cell telomere shortening may be associated
      with diabetes that shows a dramatically increased incidence with aging, beta-cell
      telomere length in diabetes has never been explored. OBJECTIVE: The objective of
      the present study was to examine telomere length in the beta-cells of patients
      with diabetes. DESIGN AND PATIENTS: We determined telomere length in beta- and
      alpha-cells of pancreases obtained at autopsy from 47 patients with type 2
      diabetes and 51 controls, all older than 60 years. MAIN OUTCOME MEASURE: The
      normalized telomere to centromere ratio (NTCR), an index of telomere length, was
      determined for beta- (NTCRbeta) and alpha- (NTCRalpha) cells by quantitative
      fluorescence in situ hybridization. RESULTS: The NTCRbeta was reduced by 27% +/-
      25% and NTCRalpha by 15% +/- 27% in the patients with diabetes relative to the
      controls (P < .01 for both). Importantly, the degree of shortening was
      significantly (P < .01) greater in beta-cells than in alpha-cells. The histogram
      of NTCR distribution was significantly skewed to the left in the patients with
      diabetes relative to the controls for both beta- and alpha-cells, indicating
      preferential depletion of longer-telomere islet cells. Glycated hemoglobin was
      negatively correlated with beta-cell telomere length, and the telomeres were
      significantly shorter in patients who had used hypoglycemic agents than in those
      who had not. CONCLUSION: The telomeres of beta-cells are shortened in patients
      with type 2 diabetes. There may be a vicious cycle involving beta-cell telomere
      attrition and sustained hyperglycemia.

PMID- 24735426
TI  - Association between vitamin D status and physical function in the severely obese.
AB  - CONTEXT: Mortality is 85% higher in severely obese subjects (body mass index
      [BMI] > 40 kg/m(2)) than in subjects with a healthy BMI; poor physical function
      may be contributory. Hypovitaminosis D is common in obese subjects and is
      associated with physical dysfunction in the elderly. OBJECTIVE: We determined the
      relationship between vitamin D status and physical function in severely obese
      subjects. DESIGN, SETTING, AND PATIENTS: We conducted a clinic-based, cross
      sectional study of severely obese subjects. Participants were stratified into
      three groups according to the Institute of Medicine (IOM) vitamin D status
      categorization. MAIN OUTCOME MEASURES: We compared levels of self-reported
      activity and times taken to walk 500 m and to ascend and descend a 17-cm step 50
      times. RESULTS: We recruited 252 subjects (age, 43.7 +/- 11.2 y; BMI, 50.7 +/-
      9.7 kg/m(2)); 25-hydroxyvitamin D (25OHD) concentrations were less than 30 nmol/L
      in 109 participants. Participants with a 25OHD > 50 nmol/L, compared to those
      with a 25OHD < 30 nmol/L, had the highest activity levels (3.1 +/- 3.4 h/wk
      versus 1.5 +/- 2.5 h/wk; P = .015) and the shortest 500-m walk times (6.2 +/- 1.1
      min versus 7.4 +/- 1.5 min; P = .003). Serum 25OHD concentrations had a weakly
      positive association with activity level (r = 0.19; P = .008) and a moderately
      negative association with 500-m walk time (r = -0.343; P < .001). CONCLUSIONS:
      Vitamin D status had a significant relationship with physical activity and
      physical function in this cohort of severely obese subjects. Low activity levels
      are likely to perpetuate the problem of hypovitaminosis D due to less time spent
      outdoors. Studies exploring the effects of vitamin D supplementation in this
      population are warranted.

PMID- 24735427
TI  - Obstructive sleep apnea and risk of osteoporosis: a population-based cohort study
      in Taiwan.
AB  - BACKGROUND: Obstructive sleep apnea (OSA) is associated with metabolic,
      endocrine, and cardiovascular diseases. It is characterized by repetitive
      episodes of apnea/hypopnea and hypoxia in tissues, which might also impact bone
      metabolism. This study investigates the possible association between OSA and
      osteoporosis. METHODS: Random samples of 1 million individuals were collected
      from Taiwan's National Health Insurance database. A total of 1377 patients with
      newly diagnosed OSA from 2000 to 2008 were recruited and compared with a matched
      cohort of 20 655 patients without OSA. All patients were tracked until an
      osteoporosis diagnosis, death, or the end of 2011. RESULTS: During the 6-year
      follow-up period, the incidence rates of osteoporosis in the OSA cohort and
      comparison group were 2.52 and 1.00 per 1000 person-years, respectively. Patients
      with OSA were found to be at 2.74 times the risk of osteoporosis than patients
      without OSA (95% confidence interval 1.69-4.44, P < .05), after adjustment for
      age, gender, diabetes, hypertension, coronary artery disease, obesity, stroke,
      hyperlipidemia, chronic kidney disease, gout, monthly income, and geographical
      location. Subgroup analysis showed that older patients and female patients had a
      higher risk for osteoporosis than their younger and male counterparts. Log-rank
      analysis revealed that patients with OSA patients had significantly higher
      cumulative incidence rates of osteoporosis than the comparison group (P < .0001).
      CONCLUSION: People diagnosed with OSA are at increased risk for subsequent
      osteoporosis.

PMID- 24735428
TI  - Effect of feeding diets based on coarse maize on productive performance, gizzard
      development and energy utilisation of laying hens.
AB  - 1. A total of 2200 White Leghorn layers were used to study the effect of feeding
      coarse maize on productive performance, gizzard weight, apparent metabolisable
      energy (AME) and egg quality parameters. 2. The experiment was a completely
      randomised design with 5 treatments, each being replicated 5 times (88 birds per
      replicate). Dietary treatments included a control diet with 600 g/kg of ground
      maize (6 mm sieve) and experimental diets with 150, 300, 450 or 600 g/kg coarse
      maize (10 mm sieve) replacing (w/w) ground maize. Diets, in mash form, were
      offered from 39 to 62 weeks of age. 3. Over the entire experimental period,
      dietary treatments had no effect on any of the production parameters, except on
      feed intake. A quadratic effect was observed for feed intake, where intake
      increased at 150 g/kg coarse maize inclusion. At higher inclusion levels of
      coarse maize, feed intake was similar to that of the control diet. But the
      differences in daily intake between dietary treatments were only around 1 g/bird
      and may not be of any biological significance. 4. Dietary treatments had no
      effect on gizzard weight, AME or egg quality. 5. The results indicate that coarse
      maize could completely replace maize in layer diets with no adverse effect on egg
      production, egg quality and dietary energy utilisation. In the current work,
      although the proportion of coarse particles (over 1 mm) increased with increasing
      inclusion levels of coarse maize, the differences in the percentage of particles
      above 1 mm between the fine control (0 g/kg coarse maize) and coarsest (600 g/kg
      coarse maize) diets was only 15%, and this may limit the value of the findings
      reported herein.

PMID- 24735429
TI  - Carbon-based nanoreporters designed for subsurface hydrogen sulfide detection.
AB  - Polyvinyl alcohol functionalized carbon black with H2S-sensor moieties can be
      pumped through oil and water in porous rock and the H2S content can be determined
      based on the fluorescent enhancement of the H2S-sensor addends. 

PMID- 24735430
TI  - Group-wise evaluation and comparison of white matter fiber strain and maximum
      principal strain in sports-related concussion.
AB  - Sports-related concussion is a major public health problem in the United States
      and yet its biomechanical mechanisms remain unclear. In vitro studies demonstrate
      axonal elongation as a potential injury mechanism; however, current response
      based injury predictors (e.g., maximum principal strain, epsilon(ep)) typically
      do not incorporate axonal orientations. We investigated the significance of white
      matter (WM) fiber orientation in strain estimation and compared fiber strain
      (epsilon(n)) with epsilon(ep) for 11 athletes with a clinical diagnosis of
      concussion. Geometrically accurate subject-specific head models with high mesh
      quality were created based on the Dartmouth Head Injury Model (DHIM), which was
      successfully validated (performance categorized as "good" to "excellent"). For WM
      regions estimated to be exposed to high strains using a range of injury
      thresholds (0.09-0.28), substantial differences existed between epsilon(n) and
      epsilon(ep) in both distribution (Dice coefficient of 0.13-0.33) and extent (~ 5
      10-fold differences), especially at higher threshold levels and higher rotational
      acceleration magnitudes. For example, an average of 3.2% vs. 29.8% of WM was
      predicted above an optimal threshold of 0.18 established from an in vivo animal
      study using epsilon(n) and epsilon(ep), respectively, with an average Dice
      coefficient of 0.14. The distribution of WM regions with high epsilon(n) was
      consistent with typical heterogeneous patterns of WM disruptions in diffuse
      axonal injury, and the group-wise extent at the optimal threshold matched well
      with the percentage of WM voxels experiencing significant longitudinal changes of
      fractional anisotropy and mean diffusivity (3.2% and 3.44%, respectively) found
      from a separate independent study. These results suggest the significance of
      incorporating WM microstructural anisotropy in future brain injury studies.

PMID- 24735431
TI  - Improvement of microcirculation and wound healing in vertical ridge augmentation
      after pre-treatment with self-inflating soft tissue expanders - a randomized
      study in dogs.
AB  - OBJECTIVES: We investigated the effect of soft tissue expansion (STE) on vertical
      ridge augmentation with regard to the incidence of wound dehiscences and the
      impairment of microcirculation in dogs, and the applicability of laser Doppler
      flowmetry (LDF) to explore the relation between microcirculation and wound
      healing. MATERIAL AND METHODS: Bone defects were created on both mandibular sides
      in ten beagle dogs by extraction of premolars and removal of bone. Six weeks
      later, self-filling tissue expanders were implanted in randomly assigned test
      sites. After 5 weeks of expansion, vertical augmentation was carried out in test
      and control sites using calvarial onlay grafts side by side with granular
      biphasic calcium phosphate covered with a resorbable polyethylene glycol
      membrane. Microcirculation was evaluated with laser Doppler flowmetry (LDF). The
      incidence of wound dehiscences was evaluated after 2 weeks. The validity of LDF
      to predict dehiscences was evaluated by construction of receiver operating
      characteristic (ROC) curves. RESULTS: After augmentation, test sites showed
      significantly better perfusion than control sites without preceding STE (P =
      0.012). Three days after surgery, perfusion was still significantly decreased in
      control sites (P = 0.005), while microcirculation in test sites had returned to
      pre-surgical levels. After 2 weeks, healing in test sites was good, whereas eight
      dehiscences were found in control sites (P = 0.002). ROC curves showed that
      microcirculation levels immediately after augmentation surgery significantly
      predicted subsequent wound dehiscences (AUC = 0.799, CI 0.642-0.955, P = 0.006).
      CONCLUSIONS: Laser Doppler flowmetry is suitable for evaluation of soft tissue
      microcirculation after ridge augmentation. STE reduced the impairment of
      microcirculation caused by vertical ridge augmentation and decreased the
      incidence of wound dehiscences in the investigated animal model.

PMID- 24735432
TI  - Independent mobility of proteins and lipids in the plasma membrane of Escherichia
      coli.
AB  - Fluidity is essential for many biological membrane functions. The basis for
      understanding membrane structure remains the classic Singer-Nicolson model, in
      which proteins are embedded within a fluid lipid bilayer and able to diffuse
      laterally within a sea of lipid. Here we report lipid and protein diffusion in
      the plasma membrane of live cells of the bacterium Escherichia coli, using
      Fluorescence Recovery after Photobleaching (FRAP) and Total Internal Reflection
      Fluorescence (TIRF) microscopy to measure lateral diffusion coefficients. Lipid
      and protein mobility within the membrane were probed by visualizing an artificial
      fluorescent lipid and a simple model membrane protein consisting of a single
      membrane-spanning alpha-helix with a Green Fluorescent Protein (GFP) tag on the
      cytoplasmic side. The effective viscosity of the lipid bilayer is strongly
      temperature-dependent, as indicated by changes in the lipid diffusion
      coefficient. Surprisingly, the mobility of the model protein was unaffected by
      changes in the effective viscosity of the bulk lipid, and TIRF microscopy
      indicates that it clusters in segregated, mobile domains. We suggest that this
      segregation profoundly influences the physical behaviour of the protein in the
      membrane, with strong implications for bacterial membrane function and bacterial
      physiology.

PMID- 24735433
TI  - Novel green-light KTP laser en bloc enucleation for nonmuscle-invasive bladder
      cancer: technique and initial clinical experience.
AB  - BACKGROUND AND PURPOSE: The standard procedure for staging and treating nonmuscle
      invasive bladder cancer (NMIBC) is still transurethral resection of bladder tumor
      (TURBT) via a wire loop. However, TURBT is associated with serious disadvantages
      that facilitate tumor recurrence. Recently, lasers have been explored as
      treatment tools for bladder tumors. Here, we report a novel tumor en bloc
      enucleation using a front-firing green-light potassium-titanyl-phosphate laser
      and its initial clinical application. PATIENTS AND METHODS: From March through
      June 2013, 45 patients with NMIBC received modified transurethral resection using
      a front-firing green-light laser. En bloc enucleation was performed on all
      tumors. Preoperative and intraoperative data were retrospectively collected.
      RESULTS: All patients successfully went through a session of treatment with front
      firing green-light laser enucleation of the bladder tumor. Complications such as
      bladder hemorrhage, vesicle perforation, and obturator nerve reflex were not
      encountered during the treatment. The tumor diameter ranges from 0.3 to 3.0 cm
      with a mean value of 1.8 cm. Mean operative time and enucleation time were 21 (12
      38) and 12 (4-23) minutes, respectively. Serum hemoglobin decreased 1.1 (0.1-2.4)
      mg/dL averagely. Mean catheter time was 2.0 (1.0-3.0) days, and mean
      postoperative hospital stay was 2.5 (1.5-4.0) days. The stages of bladder cancer
      included 27 Ta, 15 T1, and 3 T2a. No tumor recurrence was observed at the initial
      6-month follow-up. CONCLUSIONS: The modified technique using a front-firing green
      light laser to en bloc enucleate bladder tumors is effective and safe for
      treatment of NMIBC. Moreover, it may improve the accurate valuation of tumor
      stage and prediction of postoperative prognosis, although long-term outcomes and
      prospective clinical trials are needed.

PMID- 24735434
TI  - A first genetic map of date palm (Phoenix dactylifera) reveals long-range genome
      structure conservation in the palms.
AB  - BACKGROUND: The date palm is one of the oldest cultivated fruit trees. It is
      critical in many ways to cultures in arid lands by providing highly nutritious
      fruit while surviving extreme heat and environmental conditions. Despite its
      importance from antiquity, few genetic resources are available for improving the
      productivity and development of the dioecious date palm. To date there has been
      no genetic map and no sex chromosome has been identified. RESULTS: Here we
      present the first genetic map for date palm and identify the putative date palm
      sex chromosome. We placed ~4000 markers on the map using nearly 1200 framework
      markers spanning a total of 1293 cM. We have integrated the genetic map, derived
      from the Khalas cultivar, with the draft genome and placed up to 19% of the draft
      genome sequence scaffolds onto linkage groups for the first time. This analysis
      revealed approximately ~1.9 cM/Mb on the map. Comparison of the date palm linkage
      groups revealed significant long-range synteny to oil palm. Analysis of the date
      palm sex-determination region suggests it is telomeric on linkage group 12 and
      recombination is not suppressed in the full chromosome. CONCLUSIONS: Based on a
      modified genotyping-by-sequencing approach we have overcome challenges due to
      lack of genetic resources and provide the first genetic map for date palm.
      Combined with the recent draft genome sequence of the same cultivar, this
      resource offers a critical new tool for date palm biotechnology, palm comparative
      genomics and a better understanding of sex chromosome development in the palms.

PMID- 24735435
TI  - Religious coping among women with obstetric fistula in Tanzania.
AB  - Religion is an important aspect of Tanzanian culture, and is often used to cope
      with adversity and distress. This study aimed to examine religious coping among
      women with obstetric fistulae. Fifty-four women receiving fistula repair at a
      Tanzanian hospital completed a structured survey. The Brief RCOPE assessed
      positive and negative religious coping strategies. Analyses included associations
      between negative religious coping and key variables (demographics, religiosity,
      depression, social support and stigma). Forty-five women also completed
      individual in-depth interviews where religion was discussed. Although
      participants utilised positive religious coping strategies more frequently than
      negative strategies (p < .001), 76% reported at least one form of negative
      religious coping. In univariate analysis, negative religious coping was
      associated with stigma, depression and low social support. In multivariate
      analysis, only depression remained significant, explaining 42% of the variance in
      coping. Qualitative data confirmed reliance upon religion to deal with fistula
      related distress, and suggested that negative forms of religious coping may be an
      expression of depressive symptoms. Results suggest that negative religious coping
      could reflect cognitive distortions and negative emotionality, characteristic of
      depression. Religious leaders should be engaged to recognise signs of depression
      and provide appropriate pastoral/spiritual counselling and general psychosocial
      support for this population.

PMID- 24735436
TI  - Parmotrema tinctorum exhibits antioxidant, antiglycation and inhibitory
      activities against aldose reductase and carbohydrate digestive enzymes: an in
      vitro study.
AB  - This study evaluated the inhibitory potential of ethyl acetate extract of
      Parmotrema tinctorum (PTEE), an edible lichen, against aldose reductase (AR) and
      carbohydrate digestive enzymes such as alpha-glucosidase and alpha-amylase. It
      was also screened for antioxidant activities by using DPPH, ABTS, superoxide and
      hydroxyl radical-scavenging assays. PTEE exhibited alpha-glucosidase, alpha
      amylase and AR inhibition along with significant antiglycation potential with an
      estimated IC50 value of 58.45 +/- 1.24, 587.74 +/- 3.27, 139.28 +/- 2.6 and
      285.78 +/- 1.287 MUg/mL, respectively. Antioxidant activity of PTEE against DPPH
      (IC50 396.83 +/- 2.98 MUg/mL), ABTS (151.34 +/- 1.79 MUg/mL), superoxide (30.29
      +/- 1.17 MUg/mL) and hydroxyl (35.42 +/- 1.22 MUg/mL) radicals suggests the
      antioxidant potential of P. tinctorum. Significant antioxidant activity and
      inhibitory potential against carbohydrate digestive enzymes and AR suggest that
      P. tinctorum can be developed as functional food/nutraceuticals for diabetes
      after detailed study.

PMID- 24735437
TI  - Selfing ability and dispersal are positively related, but not affected by range
      position: a multispecies study on southern African Asteraceae.
AB  - Dispersal and breeding system traits are thought to affect colonization success.
      As species have attained their present distribution ranges through colonization,
      these traits may vary geographically. Although several theories predict
      associations between dispersal ability, selfing ability and the relative position
      of a population within its geographic range, there is little theoretical or
      empirical consensus on exactly how these three variables are related. We
      investigated relationships between dispersal ability, selfing ability and range
      position across 28 populations of 13 annual, wind-dispersed Asteraceae species
      from the Namaqualand region of South Africa. Controlling for phylogeny, relative
      dispersal ability--assessed from vertical fall time of fruits--was positively
      related to an index of autofertility--determined from hand-pollination
      experiments. These findings support the existence of two discrete syndromes: high
      selfing ability associated with good dispersal and obligate outcrossing
      associated with lower dispersal ability. This is consistent with the hypothesis
      that selection for colonization success drives the evolution of an association
      between these traits. However, no general effect of range position on dispersal
      or breeding system traits was evident. This suggests selection on both breeding
      system and dispersal traits acts consistently across distribution ranges.

PMID- 24735438
TI  - Theoretical study of water cluster catalyzed decomposition of formic acid.
AB  - We have performed a number of quantum chemical simulations to examine water
      cluster catalyzed decomposition of formic acid. The decomposition of formic acid
      consists of two competing pathways, dehydration, and decarboxylation. We use the
      Gaussian 4 method of the Gaussian09 software to locate and optimize a transition
      state of the decomposition reaction and obtain the activation energy. The
      decomposition starts by transferring a proton of a formic acid to a water
      molecule. The de Broglie wavelength of a proton is similar to the width of the
      potential barrier of the decomposition reaction at low temperature. The
      tunneling, in which a proton penetrates the potential barrier, enhances the
      decomposition rate. Water molecules serve as the catalyst in the decomposition
      and reduce the activation energy. The relay of a proton from a water molecule to
      a neighboring water molecule is accomplished with little change of the geometry
      of a molecule, resulting in the reduction of the activation energy. Two water
      molecules are actively involved in the decomposition reaction to reduce the
      activation energy. We have also examined the effect of water clusters with three,
      four, and five water molecules on the decomposition reaction. The noncovalent
      distance between a hydrogen atom of a water molecule and an oxygen atom of a
      neighboring water molecule decreases in a water cluster due to the cooperative
      many-body interactions. A water molecule in a water cluster becomes a better
      proton donor as well as a better proton acceptor. The activation energy of the
      decomposition is further decreased by the catalytic effect of a water cluster. We
      calculate the reaction rate using the transition state theory corrected by the
      tunneling effect of a proton. The calculated reaction rate of the decarboxylation
      is smaller than that of the dehydration when less than three water molecules are
      included in the simulation. However, the major product of the decomposition of a
      formic acid becomes carbon dioxide and hydrogen molecule formed by the
      decarboxylation when a water cluster with more than four water molecules serves
      as catalyst in the decomposition of formic acid. 

PMID- 24735439
TI  - Charged polymer brushes-grafted hollow silica nanoparticles as a novel promising
      material for simultaneous joint lubrication and treatment.
AB  - The fabrication of core/shell charged polymer brushes-grafted hollow silica
      nanoparticles (PSPMA-g-HSNPs) is reported. Because of the excellent hydration
      capability of the shells consisting of charged polymer brushes, the functional
      nanoparticles can achieve a good lubricating effect in aqueous media via
      hydration lubrication mechanism. The mesoporous hollow silica cores endow the
      nanoparticles with drug loading-release capability. Aspirin, as a useful drug for
      treating arthritis, was employed to carry out in vitro drug loading and release
      studies. It is clear that brushes-modified hollow silica exhibited long-term drug
      release performance. The combination of lubrication and drug loading capabilities
      results in the great clinical potential of new multifunctional nanoparticles as
      injectable joint lubricant fluid in arthritis treatment. 

PMID- 24735440
TI  - Modulators of protein-protein interactions.

PMID- 24735442
TI  - A BSL-4 high-throughput screen identifies sulfonamide inhibitors of Nipah virus.
AB  - Nipah virus is a biosafety level 4 (BSL-4) pathogen that causes severe
      respiratory illness and encephalitis in humans. To identify novel small molecules
      that target Nipah virus replication as potential therapeutics, Southern Research
      Institute and Galveston National Laboratory jointly developed an automated high
      throughput screening platform that is capable of testing 10,000 compounds per day
      within BSL-4 biocontainment. Using this platform, we screened a 10,080-compound
      library using a cell-based, high-throughput screen for compounds that inhibited
      the virus-induced cytopathic effect. From this pilot effort, 23 compounds were
      identified with EC50 values ranging from 3.9 to 20.0 MUM and selectivities >10.
      Three sulfonamide compounds with EC50 values <12 MUM were further characterized
      for their point of intervention in the viral replication cycle and for broad
      antiviral efficacy. Development of HTS capability under BSL-4 containment changes
      the paradigm for drug discovery for highly pathogenic agents because this
      platform can be readily modified to identify prophylactic and postexposure
      therapeutic candidates against other BSL-4 pathogens, particularly Ebola,
      Marburg, and Lassa viruses.

PMID- 24735443
TI  - A phenotypic screening approach to identify anticancer compounds derived from
      marine fungi.
AB  - This study covers the isolation, testing, and identification of natural products
      with anticancer properties. Secondary metabolites were isolated from fungal
      strains originating from a variety of marine habitats. Strain culture protocols
      were optimized with respect to growth media composition and fermentation
      conditions. From these producers, isolated compounds were screened for their
      effect on the viability and proliferation of a subset of the NCI60 panel of
      cancer cell lines. Active compounds of interest were identified and selected for
      detailed assessments and structural elucidation using nuclear magnetic resonance.
      This revealed the majority of fungal-derived compounds represented known
      anticancer chemotypes, confirming the integrity of the process and the ability to
      identify suitable compounds. Examination of effects of selected compounds on
      cancer-associated cell signaling pathways used phospho flow cytometry in
      combination with 3D fluorescent cell barcoding. In parallel, the study addressed
      the logistical aspects of maintaining multiple cancer cell lines in culture
      simultaneously. A potential solution involving microbead-based cell culture was
      investigated (BioLevitator, Hamilton). Selected cell lines were cultured in
      microbead and 2D methods and cell viability tests showed comparable compound
      inhibition in both methods (R2=0.95). In a further technology assessment, an
      image-based assay system was investigated for its utility as a possible
      complement to ATP-based detection for quantifying cell growth and viability in a
      label-free manner.

PMID- 24735444
TI  - Development of fluorescent substrates and assays for the key autophagy-related
      cysteine protease enzyme, ATG4B.
AB  - The cysteine protease ATG4B plays a role in key steps of the autophagy process
      and is of interest as a potential therapeutic target. At an early step, ATG4B
      cleaves proLC3 isoforms to form LC3-I for subsequent lipidation to form LC3-II
      and autophagosome membrane insertion. ATG4B also cleaves phosphatidylethanolamine
      (PE) from LC3-II to regenerate LC3-I, enabling its recycling for further membrane
      biogenesis. Here, we report several novel assays for monitoring the enzymatic
      activity of ATG4B. An assay based on mass spectrometric analysis and
      quantification of cleavage of the substrate protein LC3-B was developed and,
      while useful for mechanistic studies, was not suitable for high throughput
      screening (HTS). A doubly fluorescent fluorescence resonance energy transfer
      (FRET) ligand YFP-LC3B-EmGFP (FRET-LC3) was constructed and shown to be an
      excellent substrate for ATG4B with rates of cleavage similar to that for LC3B
      itself. A HTS assay to identify candidate inhibitors of ATG4B utilizing FRET-LC3
      as a substrate was developed and validated with a satisfactory Z' factor and high
      signal-to-noise ratio suitable for screening small molecule libraries. Pilot
      screens of the 1,280-member library of pharmacologically active compounds
      (LOPAC(TM)) and a 3,481-member library of known drugs (KD2) gave hit rates of
      0.6% and 0.5% respectively, and subsequent titrations confirmed ATG4B inhibitory
      activity for three compounds, both in the FRET and mass spectrometry assays. The
      FRET- and mass spectrometry-based assays we have developed will allow for both
      HTS for inhibitors of ATG4B and mechanistic approaches to study inhibition of a
      major component of the autophagy pathway.

PMID- 24735445
TI  - Multiplex analysis of anti-apoptotic BCL2 family and caspase 3 activation by
      microbead arrays.
AB  - We have developed a multiplex assay to measure the expression of anti-apoptotic
      proteins and caspase 3 activation using the Luminex platform. In this report, we
      show three applications for this assay. First, we used this assay to identify
      biomarkers for BCL2 inhibitors to obtain a quantitative measure of expression of
      anti-apoptotic proteins (BCL2, BCLxL, and MCL1) in a panel of cell lines and
      correlated their response to BCL2/BCLxL inhibitor, ABT-263 (navitoclax). Second,
      we used this assay to monitor the change of MCL1 protein expression and induction
      of active caspase 3 after treatment with cyclin-dependent kinase inhibitor
      flavopiridol. Finally, we used this assay to screen for small molecules that
      decrease MCL1 protein and identified new combinations with ABT-263. This method
      provides a quick and convenient way to measure basal expression of the anti
      apoptotic proteins and monitor expression change upon drug treatment. It is also
      applicable for high-throughput screening for compounds that decrease the
      expression of these anti-apoptotic proteins.

PMID- 24735446
TI  - Thymoquinone therapy abrogates toxic effect of cadmium on rat testes.
AB  - The protective effect of thymoquinone was investigated against cadmium-induced
      testicular toxicity in rats. Testicular toxicity was induced by a single
      intraperitoneal (i.p.) injection of cadmium chloride (2 mg kg(-1) ). Thymoquinone
      treatment (10 mg kg(-1)  day(-1) , i.p.) was applied for five consecutive days,
      starting 3 days before cadmium administration. Thymoquinone significantly
      attenuated the cadmium-induced decreases in serum testosterone, and testicular
      reduced glutathione and superoxide dismutase activity and significantly decreased
      the elevations of testicular malondialdehyde, nitric oxide and cadmium ion levels
      resulted from cadmium chloride administration. Also, thymoquinone ameliorated the
      cadmium-induced testicular tissue injury observed by histopathological
      examination. In addition, thymoquinone significantly decreased the cadmium
      induced expression of inducible nitric oxide synthase, tumour necrosis factor
      alpha, cyclooxygenase-2, nuclear factor-kappaB and caspase-3 in testicular
      tissue. It was concluded that thymoquinone, through its antioxidant and anti
      inflammatory activities, may represent a potential candidate to protect the
      testes against the detrimental effect of cadmium exposure. 

PMID- 24735447
TI  - Transition metal hexacyanoferrates in electrocatalysis of H2O2 reduction: an
      exclusive property of Prussian Blue.
AB  - The ability of Prussian Blue, ferric hexacyanoferrate (FeHCF), to sensitively and
      selectively detect hydrogen peroxide by its reduction in the presence of oxygen
      is of high importance for analytical chemistry. Success with Prussian Blue (PB)
      provided an appearance of contradictory reports concerning electrocatalysis of
      the other transition metal hexacyanoferrates (HCFs) in H2O2 reduction.
      Investigating thermodynamics of the catalyzed reactions as well as
      electrochemical properties of the hexacyanoferrates, we are able to conclude that
      the noniron hexacyanoferrates themselves are completely electrocatalytically
      inactive, except for a minor electrocatalysis in the opposite reaction, hydrogen
      peroxide oxidation, registered for NiHCF. Concerning the most important reaction,
      H2O2 reduction, the observed electrocatalytic activity (by the way, 100 times
      decreased compared to PB) is due to the presence of FeHCF (Prussian Blue) as
      defects in the structure of noniron hexacyanoferrates. This finding, considering
      other unique properties of transition metal HCFs, will provide a systematic
      search for sensing materials with improved analytical performance
      characteristics. 

PMID- 24735448
TI  - A tumor environment responsive doxorubicin-loaded nanoparticle for targeted
      cancer therapy.
AB  - Doxorubicin (DOX) is a potent cancer chemotherapeutic agent, but its clinical use
      is severely limited by potentially lethal cardiotoxicity. Delivery of DOX by
      particulate carriers can be an effective way to reduce its distribution in
      cardiac tissue. In the present study, we developed a self-assembled, tumor
      microenvironment-responsive delivery system for DOX. The core of the carrier was
      built upon the DOX/DNA intercalation, which was further combined with cationic
      gelatin (C-gel) to form the complex GDD. GDD was then packaged into a complex,
      namely, HDD, based on the electrostatic interactions between the positively
      charged C-gel and negatively charged human serum albumin (HSA). The HSA molecules
      on the surface of the complex HDD effectively helped the particle evade the
      filtration of the body when injected into the circulation and passively
      accumulate into the tumor sites. After entering the tumor tissue, where albumin
      is rapidly consumed, GDD was release from HDD and the C-gel was then digested by
      the tumor-specific matrix metalloproteinase (MMPs) to free the DOX/DNA
      intercalation. Deoxyribonucleases (DNases) in the tissue could completely destroy
      the DNA molecules to release DOX into the microenvironments. After a series of in
      vitro optimization tests, we evaluated the anticancer capacity and cardiac
      toxicity of HDD in two animal models with cancer. The results suggested that HDD
      had a higher anticancer efficacy and a significantly lower cardiotoxicity than
      free DOX. Additionally, the main components of the carrier are all clinically
      approved materials. Taken together, our present delivery system is safe and
      efficient and has high potential for further clinical trials. 

PMID- 24735449
TI  - Porphyrin triplet state as a potential spin label for nanometer distance
      measurements by PELDOR spectroscopy.
AB  - This work demonstrates, for the first time, the feasibility of applying pulsed
      electron-electron double resonance (PELDOR/DEER) to determine the interspin
      distance between a photoexcited porphyrin triplet state (S = 1) and a nitroxide
      spin label chemically incorporated into a small helical peptide. The PELDOR trace
      shows deep envelope modulation induced by electron-electron dipole interaction
      between the partners in the pair, providing an accurate distance measurement.
      This new labeling approach has a high potential for measuring nanometer distances
      in more complex biological systems due to the sensitivity acquired from the spin
      polarization of the photoexcited triplet state spectrum. 

PMID- 24735450
TI  - Association of socioeconomic status in childhood with major depression and
      generalized anxiety disorder: results from the World Mental Health Japan survey
      2002-2006.
AB  - BACKGROUND: Low socioeconomic status (SES) in childhood is known to be a
      significant risk factor for mental disorders in Western societies. The purpose of
      this study was to investigate whether a similar association exists in Japan.
      METHODS: We used data from the World Mental Health Japan Survey conducted from
      2002-2006 (weighted N=1,682). Respondents completed diagnostic interviews that
      assessed lifetime prevalence of major depression (MD) and generalized anxiety
      disorder (GAD), as defined by the Diagnostic and Statistical Manual of Mental
      Disorders, Fourth Edition. Associations between parental education (a proxy of
      SES in childhood) and lifetime onset of both disorders were estimated and
      stratified by gender using discrete-time survival analysis. RESULTS: Among women,
      high parental education was positively associated with MD (odds ratio [OR]: 1.81,
      95% confidence interval [CI]: 1.03-3.18) in comparison with low parental
      education, even after adjustment for age, childhood characteristics, and SES in
      adulthood. This same effect was not found for men. In contrast, higher parental
      education was associated with GAD (OR: 6.84, 95% CI: 1.62-28.94) in comparison
      with low parental education among men, but this association was not found among
      the women, in the fully adjusted model. CONCLUSIONS: In Japan, childhood SES is
      likely to be positively associated with the lifetime onset of mental disorders,
      regardless of family history of mental disorders, childhood physical illness, or
      SES in adulthood. Further study is required to replicate the current findings and
      elucidate the mechanism of the positive association between mental disorders and
      childhood SES.

PMID- 24735451
TI  - "Clozapine makes me quite drowsy, so when I wake up in the morning those first
      cups of coffee are really handy": an exploratory qualitative study of excessive
      caffeine consumption among individuals with schizophrenia.
AB  - BACKGROUND: Research has shown that individuals with schizophrenia use caffeine
      at higher rates than the general population; however, no qualitative research has
      been undertaken investigating problematic caffeine use and its effects on this
      population. This article explores the role of caffeine consumption in the lives
      of people with schizophrenia through a narrative analysis of the attitudes and
      beliefs associated with this practice, and how these, in turn, influence caffeine
      consumption. METHODS: A qualitative study was undertaken with individuals who had
      previously scored in either a 'moderate' or 'high' risk category for caffeine use
      on the Alcohol, Smoking and Substance Involvement Screening Tool (ASSIST). In
      depth interviews were undertaken with 20 individuals, and transcripts were
      analysed thematically to identify prominent perspectives. RESULTS: Consistent
      with previous literature, participants' caffeine consumption was driven largely
      by its stimulating properties; however, participants also identified 'cravings'
      as an important motivating factor. Participants' behaviours related to caffeine
      consumption seemed to be tempered by their previous experiences of consumption;
      if participants had experienced positive effects such as alertness or relaxation
      in the past, their use was maintained at a similar level or increased.
      Conversely, participants who anticipated negative consequences often altered
      their patterns of caffeine consumption; for example, by substituting caffeinated
      drinks that minimised or ceased their experience of negative side effects for
      those that directly caused such impacts. Overall, participants largely identified
      caffeine consumption as a highly meaningful activity, which provided structure to
      their day and facilitated opportunities for social interaction. CONCLUSIONS: The
      inconsistencies between individuals' beliefs about their health and the actual
      risk of harm associated with health-related behaviours present significant and
      ongoing challenges for the implementation of relevant and effective strategies
      for health promotion among individuals diagnosed with mental illness. As a
      starting point, it would be worthwhile for services engaging with people
      diagnosed with mental illness, and in particular schizophrenia, to consider
      implementing caffeine-related health literacy strategies to educate consumers
      about the risk of excessive caffeine consumption and the interactions between
      caffeine and antipsychotic medications.

PMID- 24735452
TI  - Interleukin-33 requires CMRF35-like molecule-1 expression for induction of
      myeloid cell activation.
AB  - BACKGROUND: IL-33 is a potent activator of various cells involved in allergic
      inflammation, including eosinophils and mast cells. Despite its critical role in
      Th2 disease settings, endogenous molecular mechanisms that may regulate IL-33
      induced responses remain to be defined. We have recently shown that eosinophils
      express CMRF35-like molecule (CLM)-1. Yet, the role of CLM-1 in regulating
      eosinophil functions is still elusive. METHODS: CLM-1 and CLM-8 expression and
      cellular localization were assessed in murine bone marrow-derived and/or
      peritoneal cells at baseline and following IL-33 stimulation (flow cytometry,
      western blot). IL-33-induced mediator release and signaling were assessed in wild
      type (wt) and Clm1(-/-) cells and mice. RESULTS: BM-derived eosinophils express
      high levels of glycosylated CLM-1. IL-33 induced a rapid, specific, concentration
      and time-dependent upregulation of CLM-1 in eosinophils (in vitro and in vivo).
      Clm1(-/-) eosinophils secreted less IL-33-induced mediators than wt eosinophils.
      CLM-1 co-localized to ST2 following IL-33 stimulation and was required for IL-33
      induced NFkappaB and p38 phosphorylation. Th2 cytokine (e.g., IL-5, IL-13) and
      chemokine (e.g., eotaxins, CCL2) secretion was markedly attenuated in IL-33
      treated Clm1(-/-) mice. Subsequently, IL-33-challenged mice displayed reduced
      infiltration of mast cells, macrophages, neutrophils, and B cells. Despite the
      markedly impaired IL-33-induced eotaxin expression in Clm1(-/-) mice, eosinophil
      accumulation was similar in wt and Clm1(-/-) mice, due to hyperchemotactic
      responses of Clm1(-/-) eosinophils. CONCLUSIONS: CLM-1 is a novel regulator of IL
      33-induced eosinophil activation. These data contribute to the understanding of
      endogenous molecular mechanisms regulating IL-33-induced responses and may
      ultimately lead to receptor-based tools for future therapeutic intervention in IL
      33-associated diseases.

PMID- 24735453
TI  - Driving the bumpy road to commercialization.
AB  - Tissue engineering has always had an applied focus and there is hardly an
      academic publication that does not mention the applicability of its findings to
      the future development of a medical product. I have been involved in the industry
      side of tissue engineering from the start, pursuing a variety of applications,
      some making it to the marketplace. There have been many lessons that I have
      learned from direct experience (mistakes and successes), observation, through
      advising others, and now, in developing innovative ways to identify and eliminate
      the regenerative cell populations within a tumor. This brief overview of some of
      these lessons is written with the next generation of pioneering product
      developers in mind: the biologists, biochemists, and engineers who will dedicate
      their careers to driving medical and commercial progress in tissue engineering. 

PMID- 24735455
TI  - Increasing the scale and adoption of population health interventions: experiences
      and perspectives of policy makers, practitioners, and researchers.
AB  - BACKGROUND: Decisions to scale up population health interventions from small
      projects to wider state or national implementation is fundamental to maximising
      population-wide health improvements. The objectives of this study were to
      examine: i) how decisions to scale up interventions are currently made in
      practice; ii) the role that evidence plays in informing decisions to scale up
      interventions; and iii) the role policy makers, practitioners, and researchers
      play in this process. METHODS: Interviews with an expert panel of senior
      Australian and international public health policy-makers (n = 7), practitioners
      (n = 7), and researchers (n = 7) were conducted in May 2013 with a participation
      rate of 84%. RESULTS: Scaling up decisions were generally made through iterative
      processes and led by policy makers and/or practitioners, but ultimately approved
      by political leaders and/or senior executives of funding agencies. Research
      evidence formed a component of the overall set of information used in decision
      making, but its contribution was limited by the paucity of relevant intervention
      effectiveness research, and data on costs and cost effectiveness. Policy makers,
      practitioners/service managers, and researchers had different, but complementary
      roles to play in the process of scaling up interventions. CONCLUSIONS: This
      analysis articulates the processes of how decisions to scale up interventions are
      made, the roles of evidence, and contribution of different professional groups.
      More intervention research that includes data on the effectiveness, reach, and
      costs of operating at scale and key service delivery issues (including
      acceptability and fit of interventions and delivery models) should be sought as
      this has the potential to substantially advance the relevance and ultimately
      usability of research evidence for scaling up population health action.

PMID- 24735454
TI  - Cell-type-specific Jumonji histone demethylase gene expression in the healthy rat
      CNS: detection by a novel flow cytometry method.
AB  - Our understanding of how histone demethylation contributes to the regulation of
      basal gene expression in the brain is largely unknown in any injury model, and
      especially in the healthy adult brain. Although Jumonji genes are often regulated
      transcriptionally, cell-specific gene expression of Jumonji histone demethylases
      in the brain remains poorly understood. Thus, in the present study we profiled
      the mRNA levels of 26 Jumonji genes in microglia (CD11b+), neurons (NeuN+) and
      astrocytes (GFAP+) from the healthy adult rat brain. We optimized a method
      combining a mZBF (modified zinc-based fixative) and FCM (flow cytometry) to
      simultaneously sort cells from non-transgenic animals. We evaluated cell-surface,
      intracellular and nuclear proteins, including histones, as well as messenger- and
      micro-RNAs in different cell types simultaneously from a single-sorted sample. We
      found that 12 Jumonji genes were differentially expressed between adult
      microglia, neurons and astrocytes. While JMJD2D was neuron-restricted, PHF8 and
      JMJD1C were expressed in all three cell types although the expression was highest
      in neurons. JMJD3 and JMJD5 were expressed in all cell types, but were highly
      enriched in microglia; astrocytes had the lowest expression of UTX and JHDM1D.
      Levels of global H3K27 (H3 lysine 27) methylation varied among cell types and
      appeared to be lowest in microglia, indicating that differences in basal gene
      expression of specific Jumonji histone demethylases may contribute to cell
      specific gene expression in the CNS (central nervous system). This
      multiparametric technique will be valuable for simultaneously assaying chromatin
      modifications and gene regulation in the adult CNS.

PMID- 24735456
TI  - Ethical dilemmas experienced by speech-language pathologists working in private
      practice.
AB  - Speech-language pathologists experience ethical dilemmas as they fulfil their
      professional roles and responsibilities. Previous research findings indicated
      that speech-language pathologists working in publicly funded settings identified
      ethical dilemmas when they managed complex clients, negotiated professional
      relationships, and addressed service delivery issues. However, little is known
      about ethical dilemmas experienced by speech-language pathologists working in
      private practice settings. The aim of this qualitative study was to describe the
      nature of ethical dilemmas experienced by speech-language pathologists working in
      private practice. Data were collected through semi-structured interviews with 10
      speech-language pathologists employed in diverse private practice settings.
      Participants explained the nature of ethical dilemmas they experienced at work
      and identified their most challenging and frequently occurring ethical conflicts.
      Qualitative content analysis was used to analyse transcribed data and generate
      themes. Four themes reflected the nature of speech-language pathologists' ethical
      dilemmas; balancing benefit and harm, fidelity of business practices,
      distributing funds, and personal and professional integrity. Findings support the
      need for professional development activities that are specifically targeted
      towards facilitating ethical practice for speech-language pathologists in the
      private sector.

PMID- 24735457
TI  - Adolf Beck: a forgotten pioneer in electroencephalography.
AB  - Adolf Beck, born in 1863 at Cracow (Poland), joined the Department of Physiology
      of the Jagiellonian University in 1880 to work directly under the supervision of
      the prominent physiology professor, Napoleon Cybulski. Following his suggestion,
      Beck started experimental studies on the electrical brain activity of animals,
      especially in response to sensory stimulation. Beck placed electrodes directly on
      the surface of brain to localize brain potentials that were evoked by sensory
      stimuli. He observed spontaneous fluctuations in the electrical brain activity
      and noted that these oscillations ceased after sensory stimulation. He published
      these findings concerning the electrical brain activity, such as spontaneous
      fluctuations, evoked potentials, and desynchronization of brain waves, in 1890 in
      the German language Centralblatt fur Physiologie. Moreover, an intense polemic
      arose between physiologists of that era on the question of who should claim being
      the founder of electroencephalography. Ultimately, Richard Caton from Liverpool
      showed that he had performed similar experiments in monkeys years earlier.
      Nevertheless, Beck added new elements to the nature of electrical brain activity.
      In retrospect, next to Richard Caton, Adolf Beck can be regarded, together with
      Hans Berger who later introduced the method to humans, as one of the founders of
      electroencephalography. Soon after his success, Beck got a chair at the
      Department of Physiology of the University at Lemberg, now Lviv National Medical
      University. 

PMID- 24735458
TI  - Marginal bone and soft tissue behavior following platform switching abutment
      connection/disconnection--a dog model study.
AB  - OBJECTIVE: The effect on the marginal peri-implant tissues following repeated
      platform switching abutment removal and subsequent reconnection was studied.
      MATERIAL AND METHODS: Six adult female Beagle dogs were selected, and Pm3 and Pm4
      teeth, both left and right sides, were extracted and the sites healed for 3
      months. At this time, 24 bone level (BL) (Straumann, Basel, Switzerland) O 3.3/8
      mm implants were placed, 2 in each side on Pm3 and Pm4 regions. In one side
      (control group), 12 bone level conical O 3.6 mm healing abutments and, on the
      other side (test group), 12 Narrow CrossFit (NC) multibase abutments (Straumann)
      , Basel, Switzerland) were connected at time of implant surgery. On test group,
      all prosthetic procedures were carried out direct to multibase abutment without
      disconnecting it, where in the control group, the multibase abutment was
      connected/disconnected five times (at 6/8/10/12/14 weeks) during prosthetic
      procedures. Twelve fixed metal bridges were delivered 14 weeks after implant
      placement. A cleaning/control appointment was scheduled 6 months after implant
      placement. The animals were sacrificed at 9 months of the study. Clinical
      parameters and peri-apical x-rays were registered in every visit.
      Histomorphometric analysis was carried out for the 24 implants. The distance from
      multibase abutment shoulder to the first bone implant contact (S-BIC) was defined
      as the primary histomorphometric parameter. RESULTS: Wilcoxon comparison paired
      test (n = 6) found no statistically significant differences (buccal P = 0.917;
      Lingual P = 0.463) between test and control groups both lingually and buccally
      for S-BIC distance. Only Pm3 buccal aBE-BC (distance from the apical end of the
      barrier epithelium to the first bone implant contact) (P = 0.046) parameter
      presented statistically significant differences between test and control groups.
      Control group presented 0.57 mm more recession than test group, being this
      difference statistically significant between the two groups (P < 0.001).
      CONCLUSION: It can be conclude, within the limits of this animal study, that the
      connection/disconnection of platform switching abutments during prosthetic phase
      of implant treatment does not induce bone marginal absorption. Furthermore, it
      may present a negative influence in the buccal connective tissue attachment that
      becomes shorter anyway preventing marginal hard tissue resorption, especially in
      thin biotypes.

PMID- 24735459
TI  - Trends in the incidence of and survival rates for oral cavity cancer in the
      Korean population.
AB  - OBJECTIVE: This study assessed trends in the incidence of and survival rates for
      oral cavity cancer in the Korean population. MATERIALS AND METHODS: Data from the
      Korea Central Cancer Registry were extracted for 10,282 patients diagnosed with
      oral cavity cancer (C01-C06) between 1999 and 2010 to evaluate the age
      standardised incidence rate, annual percentage change (APC) and 5-year relative
      survival rate (RSR) according to gender and age. RESULTS: In males, the incidence
      rate slightly decreased [APC of -0.2% (P = 0.6427)]; in females, the incidence
      rate increased [APC of 3.1% (P < 0.05)]. In males and females, the incidence of
      oral tongue cancer (C02) significantly increased [APC of 2.2% and 4.1%,
      respectively (P < 0.05)]. This increase in oral tongue cancer incidence was most
      prominent in the younger age group (<40 years, APC = 6.1%, P < 0.05). The
      incidence of buccal cheek cancer increased only among males [APC of 4.8% (P <
      0.05)]. The 5-year RSR improved from 42.7% (1993-1995) to 59.5% (2006-2010),
      corresponding to an increase of 16.8% from 1993 to 2010 (P < 0.05). CONCLUSION:
      The incidence of oral cavity cancer in females increased, whereas it stabilised
      or decreased in males. However, the incidence of oral tongue cancer increased in
      both males and females, especially in the younger age group.

PMID- 24735461
TI  - Correction: Determining the degradation efficiency and mechanisms of ethyl violet
      using HPLC-PDA-ESI-MS and GC-MS.
AB  - This is a correction to the following paper: Determining the degradation
      efficiency and mechanisms of ethyl violet using HPLC-PDA-ESI-MS and GC-MS, Wen
      Hsin Chung, Chung-Shin Lu, Wan-Yu Lin, Jian-Xun Wang, Chia-Wei Wu, Chiing-Chang
      Chen, Chemistry Central Journal 2012, 6:63 (30 June 2012). 

PMID- 24735460
TI  - Area 4 has layer IV in adult primates.
AB  - There are opposing views about the status of layer IV in the primary motor cortex
      (area 4). Cajal described a layer IV in area 4 of adult humans. In contrast,
      Brodmann found layer IV in developmental but not in adult primates and called
      area 4 'agranular'. We addressed this issue in rhesus monkeys using the neural
      marker SMI-32, which labels neurons in lower layer III and upper layer V, but not
      in layer IV. SMI-32 delineated a central unlabeled cortical stripe in area 4 that
      corresponds to layer IV, which was populated with small interneurons also found
      in layer IV in 'granular' areas (such as area 46). We distinguished layer IV
      interneurons from projection neurons in the layers above and below using cellular
      criteria. The commonly used term 'agranular' for area 4 is also used for the
      phylogenetically ancient limbic cortices, confusing areas that differ markedly in
      laminar structure. This issue pertains to the systematic variation in the
      architecture across cortices, traced from limbic cortices through areas with
      increasingly more elaborate laminar structure. The principle of systematic
      variation can be used to predict laminar patterns of connections across cortical
      systems. This principle places area 4 and agranular anterior cingulate cortices
      at opposite poles of the graded laminar differentiation of motor cortices. The
      status of layer IV in area 4 thus pertains to core organisational features of the
      cortex, its connections and evolution. 

PMID- 24735462
TI  - Cellular uptake of substrate-initiated cell-penetrating poly(disulfide)s.
AB  - Substrate-initiated, self-inactivating, cell-penetrating poly(disulfide)s
      (siCPDs) are introduced as general transporters for the covalent delivery of
      unmodified substrates of free choice. With ring-opening disulfide-exchange
      polymerization, we show that guanidinium-rich siCPDs grow on fluorescent
      substrates within minutes under the mildest conditions. The most active siCPD
      transporters reach the cytosol of HeLa cells within 5 min and depolymerize in
      less than 1 min to release the native substrate. Depolymerized right after use,
      the best siCPDs are nontoxic under conditions where cell-penetrating peptides
      (CPPs) are cytotoxic. Intracellular localization (cytosol, nucleoli, endosomes)
      is independent of the substrate and can be varied on demand, through choice of
      polymer composition. Insensitivity to endocytosis inhibitors and classical
      structural variations (hydrophobicity, aromaticity, branching, boronic acids)
      suggest that the best siCPDs act differently. Supported by experimental evidence,
      a unique combination of the counterion-mediated translocation of CPPs with the
      underexplored, thiol-mediated covalent translocation is considered to account for
      this decisive difference. 

PMID- 24735463
TI  - Horizontal transfer of the msp130 gene supported the evolution of metazoan
      biomineralization.
AB  - It is widely accepted that biomineralized structures appeared independently in
      many metazoan clades during the Cambrian. How this occurred, and whether it
      involved the parallel co-option of a common set of biochemical and developmental
      pathways (i.e., a shared biomineralization "toolkit"), are questions that remain
      unanswered. Here, I provide evidence that horizontal gene transfer supported the
      evolution of biomineralization in some metazoans. I show that Msp130 proteins,
      first described as proteins expressed selectively by the biomineral-forming
      primary mesenchyme cells of the sea urchin embryo, have a much wider taxonomic
      distribution than was previously appreciated. Msp130 proteins are present in
      several invertebrate deuterostomes and in one protostome clade (molluscs).
      Surprisingly, closely related proteins are also present in many bacteria and
      several algae, and I propose that msp130 genes were introduced into metazoan
      lineages via multiple, independent horizontal gene transfer events. Phylogenetic
      analysis shows that the introduction of an ancestral msp130 gene occurred in the
      sea urchin lineage more than 250 million years ago and that msp130 genes
      underwent independent, parallel duplications in each of the metazoan phyla in
      which these genes are found. 

PMID- 24735465
TI  - Single molecule studies of force-induced S2 site exposure in the mammalian Notch
      negative regulatory domain.
AB  - Notch signaling in metazoans is responsible for key cellular processes related to
      embryonic development and tissue homeostasis. Proteolitic cleavage of the S2 site
      within an extracellular NRR domain of Notch is a key early event in Notch
      signaling. We use single molecule force-extension (FX) atomic force microscopy
      (AFM) to study force-induced exposure of the S2 site in the NRR domain from mouse
      Notch 1. Our FX AFM measurements yield a histogram of N-to-C termini lengths,
      which we relate to conformational transitions within the NRR domain. We detect
      four classes of such conformational transitions. From our steered molecular
      dynamics (SMD) results, we associate first three classes of such events with the
      S2 site exposure. AFM experiments yield their mean unfolding forces as 69 +/- 42,
      79 +/- 45, and 90 +/- 50 pN, respectively, at 400 nm/s AFM pulling speeds. These
      forces are matched by the SMD results recalibrated to the AFM force loading
      rates. Next, we provide a conditional probability analysis of the AFM data to
      support the hypothesis that a whole sequence of conformational transitions within
      those three clases is the most probable pathway for the force-induced S2 site
      exposure. Our results support the hypothesis that force-induced Notch activation
      requires ligand binding to exert mechanical force not in random but in several
      strokes and over a substantial period of time. 

PMID- 24735464
TI  - Plastid and mitochondrion genomic sequences from Arctic Chlorella sp. ArM0029B.
AB  - BACKGROUND: Chorella is the representative taxon of Chlorellales in
      Trebouxiophyceae, and its chloroplast (cp) genomic information has been thought
      to depend only on studies concerning Chlorella vulgaris and GenBank information
      of C. variablis. Mitochondrial (mt) genomic information regarding Chlorella is
      currently unavailable. To elucidate the evolution of organelle genomes and
      genetic information of Chlorella, we have sequenced and characterized the cp and
      mt genomes of Arctic Chlorella sp. ArM0029B. RESULTS: The 119,989-bp cp genome
      lacking inverted repeats and 65,049-bp mt genome were sequenced. The ArM0029B cp
      genome contains 114 conserved genes, including 32 tRNA genes, 3 rRNA genes, and
      79 genes encoding proteins. Chlorella cp genomes are highly rearranged except for
      a Chlorella-specific six-gene cluster, and the ArM0029B plastid resembles that of
      Chlorella variabilis except for a 15-kb gene cluster inversion. In the mt genome,
      62 conserved genes, including 27 tRNA genes, 3 rRNA genes, and 32 genes encoding
      proteins were determined. The mt genome of ArM0029B is similar to that of the non
      photosynthetic species Prototheca and Heicosporidium. The ArM0029B mt genome
      contains a group I intron, with an ORF containing two LAGLIDADG motifs, in cox1.
      The intronic ORF is shared by C. vulgaris and Prototheca. The phylogeny of the
      plastid genome reveals that ArM0029B showed a close relationship of Chlorella to
      Parachlorella and Oocystis within Chlorellales. The distribution of the cox1
      intron at 721 support membership in the order Chlorellales. Mitochondrial
      phylogenomic analyses, however, indicated that ArM0029B shows a greater affinity
      to MX-AZ01 and Coccomyxa than to the Helicosporidium-Prototheca clade, although
      the detailed phylogenetic relationships among the three taxa remain to be
      resolved. CONCLUSIONS: The plastid genome of ArM0029B is similar to that of C.
      variabilis. The mt sequence of ArM0029B is the first genome to be reported for
      Chlorella. Chloroplast genome phylogeny supports monophyly of the seven
      investigated members of Chlorellales. The presence of the cox1 intron at 721 in
      all four investigated Chlorellales taxa indicates that the cox1 intron had been
      introduced in early Chorellales as a cis-splice form and that the cis-splicing
      intron was inherited to recent Chlorellales and was recently trans-spliced in
      Helicosporidium.

PMID- 24735466
TI  - Violent conflict and population health in the Middle East.

PMID- 24735467
TI  - The practice of humanitarianism: a village birthing clinic in Palestine.
AB  - Discourses and practices surrounding humanitarian organisations have changed over
      time. This is certainly the case for Palestinian non-governmental organisations,
      which have followed the structural and ideological transformations observed in
      local, regional and international contexts. There have been three successive but
      interlocking generations of groups active in health in Palestine: charitable
      societies, popular committees, and donor-based entities. Against this background,
      a village clinic in the West Bank is seen to have gone through various
      incarnations in the context of an emerging neo-liberal economic, administrative
      and political environment. Despite the critiques justifiably addressed towards
      them, non-governmental organisations may in some cases be functionally fluid.
      Communities and people continue to use them strategically in their relations with
      states, political groups, individuals and receivers of aid, making them potential
      networking sites in the context of an ongoing occupation.

PMID- 24735468
TI  - Probing rotational and translational diffusion of nanodoublers in living cells on
      microsecond time scales.
AB  - Nonlinear microscopes have seen an increase in popularity in the life sciences
      due to their molecular and structural specificity, high resolution, large
      penetration depth, and volumetric imaging capability. Nonetheless, the inherently
      weak optical signals demand long exposure times for live cell imaging. Here, by
      modifying the optical layout and illumination parameters, we can follow the
      rotation and translation of noncentrosymetric crystalline particles, or
      nanodoublers, with 50 MUs acquisition times in living cells. The rotational
      diffusion can be derived from variations in the second harmonic intensity that
      originates from the rotation of the nanodoubler crystal axis. We envisage that by
      capitalizing on the biocompatibility, functionalizability, stability, and
      nondestructive optical response of the nanodoublers, novel insights on cellular
      dynamics are within reach. 

PMID- 24735470
TI  - The presence, function and regulation of IL-17 and Th17 cells in periodontitis.
AB  - Periodontitis (PD) is a chronic inflammatory disease characterised by tissue
      inflammation and destruction of the associated alveolar bone. It is caused by the
      colonisation of the bacterial plaque biofilm and the resultant host immune
      responses in the surrounding periodontal tissues. The pro-inflammatory cytokine
      IL-17, and IL-17 producing CD4+ T cells (also called Th17 cells) have been shown
      to play an important role in many inflammatory diseases. There is increasing
      evidence of the presence of IL-17 and Th17 cells in human PD lesions and this may
      be associated with disease severity. Moreover, several animal studies indicate
      the potential role of IL-17 and Th17 cells in gingival inflammation and the
      resultant bone destruction in PD. Here we review recent findings regarding the
      presence, function and regulation of IL-17 and Th17 cells in PD, and we highlight
      potential areas of future research interest. 

PMID- 24735469
TI  - Does the primary screening test influence women's anxiety and intention to screen
      for cervical cancer? A randomized survey of Norwegian women.
AB  - BACKGROUND: Countries must decide whether or not to replace primary cytology
      based screening with primary human papillomavirus (HPV)-based screening. We aimed
      to assess how primary screening for an HPV infection, a sexually transmitted
      infection (STI), and the type of information included in the invitation letter,
      will affect screening intention. METHODS: We randomized a representative sample
      of Norwegian women to one of three invitation letters: 1) Pap smear, 2) HPV
      testing or 3) HPV testing with additional information about the nature of the
      infection. Intention to participate, anxiety level and whether women intend to
      follow-up abnormal results were measured between groups using chi-squared and
      nonparametric Kruskal-Wallis tests. Determinants of intention were explored using
      logistic regression. RESULTS: Responses from 3540 women were representative of
      the Norwegian population with respect to age, civil status and geographic
      location. No significant difference across invitation letters was found in
      women's stated intention to participate (range: 91.8-92.3%), anxiety (39-42% were
      either quite or very worried) or to follow-up after an abnormal result (range:
      97.1-97.6%). Strength of intention to participate was only marginally lower for
      HPV-based invitation letters, albeit significant (p-value = 0.008), when measured
      on a scale. Only 36-40% of respondents given the HPV invitations correctly
      understood that they likely had an STI. CONCLUSIONS: We found that switching to
      primary HPV screening, independent of additional information about HPV
      infections, is not likely to reduce screening participation rates or increase
      anxiety; however, women lacked the ability to interpret the meaning of an HPV
      test result.

PMID- 24735471
TI  - Effect of day length on flock behavioural patterns and melatonin rhythms in
      broilers.
AB  - 1. Ross * Ross 308 male broilers were used to study the impact of 14, 17, 20 and
      23 h of light (L) on flock behavioural patterns and 24 h melatonin rhythm
      synchrony during the photophase. 2. Behaviour in two pens (n = 53) per lighting
      treatment was digitally recorded for 24 h in trial 1 (27-28 d of age (d 27)) and
      two (42-43 d (d 42)), and quantified using a scan sampling technique at 10 min
      intervals. Regression procedures were used to test flock trend analysis between
      behavioural (resting, standing, walking and feeding) variables and time during
      the photophase. 3. The presence of a flock melatonin rhythm was determined by
      radioimmunoassay of blood samples collected at 6 times for birds raised on 23L
      and 8 times for 14, 17 and 20L birds (n = 6 per time) over a 24 h period (d 21)
      in experiment 1. 4. Quadratic and linear relationships between time and behaviour
      during the photophase were frequent in 14L and 17L birds, sporadic in 20L birds
      and non-existent in 23L birds. Relationships were noted in inactive resting (d
      27: 14L and 17L; d 42: 14L and 20L), walking (d 27: 14L and 17L), standing (d 27
      and d 42: 14L, 17L and 20L) and feeding (d 27: 14L and 17L). A quadratic time *
      melatonin relationship existed in 14L, 17L and 20L flocks only. 5. Behaviour
      during the photophase and 24 h melatonin production indicates that flocks exposed
      to 23L do not develop synchronised rhythms, increasing the risk of suffering from
      sleep fragmentation.

PMID- 24735472
TI  - Embryonic development in the ostrich (Struthio camelus) during the first 7 days
      of artificial incubation.
AB  - 1. Early development of ostrich embryos was investigated in relation to time of
      egg collection and genotype. 2. A total of 321 ostrich eggs were collected during
      the 2008 and 2009 breeding seasons and the development of the embryo for up to
      the first 168 h of incubation was described and analysed. A sample of the
      incubated eggs was weighed and opened daily to investigate developmental changes.
      3. In fresh eggs, the blastoderm contained a round, translucent dark area
      pellucida (AP) in the centre, with a surrounding thin white ring, likely to be
      the beginning of the area opaca (AO). Fresh eggs were considered infertile if the
      blastoderm was absent and instead numerous white droplets were present surrounded
      by vacuoles. 4. The average blastoderm area of a fresh fertile egg was 15.8
      mm(2), increasing to 143.3 mm(2) after 2 d of incubation. By 72 h of incubation
      the area vasculosa (AV) was discernible in the posterior half of the blastoderm.
      5. At 48 h of incubation the blastoderm area in eggs from the South African Black
      genotype (SAB) * Zimbabwean Blue genotype (ZB) crosses (104.5 +/- 18.6 mm(2)) was
      lower than the pure SAB (141.0 +/- 10.5 mm(2)), ZB (161.7 +/- 13.5 mm(2)) and ZB
      * SAB crosses (166.1 +/- 14.2 mm(2)). 6. Embryo length was 5.01 mm after 72 h of
      incubation and 14.5 mm after 168 h of incubation. At 168 h of incubation AV
      lengths for both ZB * SAB (53.2 mm) and SAB * ZB crosses (54.1 mm) were longer
      than in embryos from the pure breeds. 7. Results from this study can be put to
      practical use when determining whether eggs are infertile or fertile and also in
      investigating the age of early embryonic mortalities.

PMID- 24735473
TI  - Bioavailability and pharmacokinetic profile of levofloxacin following
      intravenous, intramuscular and oral administration in turkeys.
AB  - 1. The pharmacokinetics and bioavailability of levofloxacin in turkeys were
      investigated after a single intravenous (IV), intramuscular (IM) and oral (PO)
      administration of 10 mg/kg body weight. 2. The concentrations of levofloxacin in
      plasma samples were assayed using a microbiological assay method and
      pharmacokinetic parameters were calculated by non-compartmental analysis. 3.
      Following IV administration, the elimination half-life (t0.5(beta)), volume of
      distribution at steady state (Vdss) and total body clearance (Cl) were 4.49 h,
      1.31 l/kg and 0.23 l/h/kg, respectively. 4. After single IM and PO
      administrations at the same dose, levofloxacin was rapidly absorbed as indicated
      by an absorption half-life (t0.5ab) of 1.02 and 0.76 h, respectively; maximum
      plasma concentrations (Cmax) of 5.59 and 5.15 MUg/ml were obtained at a maximum
      time (Tmax) of 2 h for both routes and levofloxacin bioavailability (F) was 96.5
      h and 79.9% respectively after IM and PO administration. In vitro plasma protein
      binding of levofloxacin was 24.3%. 5. Based on these pharmacokinetic parameters,
      a dose of 10 mg/kg body weight given intramuscularly or orally every 24 h in
      turkeys can maintain effective plasma concentrations with bacterial infections
      with (minimum inhibitory concentration) MIC90 > 0.1 MUg/ml.

PMID- 24735474
TI  - A comparison of computational models with and without genotyping for prediction
      of response to second-line HIV therapy.
AB  - OBJECTIVES: We compared the use of computational models developed with and
      without HIV genotype vs. genotyping itself to predict effective regimens for
      patients experiencing first-line virological failure. METHODS: Two sets of models
      predicted virological response for 99 three-drug regimens for patients on a
      failing regimen of two nucleoside/nucleotide reverse transcriptase inhibitors and
      one nonnucleoside reverse transcriptase inhibitor in the Second-Line study. One
      set used viral load, CD4 count, genotype, plus treatment history and time to
      follow-up to make its predictions; the second set did not include genotype.
      Genotypic sensitivity scores were derived and the ranking of the alternative
      regimens compared with those of the models. The accuracy of the models and that
      of genotyping as predictors of the virological responses to second-line regimens
      were compared. RESULTS: The rankings of alternative regimens by the two sets of
      models were significantly correlated in 60-69% of cases, and the rankings by the
      models that use a genotype and genotyping itself were significantly correlated in
      60% of cases. The two sets of models identified alternative regimens that were
      predicted to be effective in 97% and 100% of cases, respectively. The area under
      the receiver-operating curve was 0.72 and 0.74 for the two sets of models,
      respectively, and significantly lower at 0.55 for genotyping. CONCLUSIONS: The
      two sets of models performed comparably well and significantly outperformed
      genotyping as predictors of response. The models identified alternative regimens
      predicted to be effective in almost all cases. It is encouraging that models that
      do not require a genotype were able to predict responses to common second-line
      therapies in settings where genotyping is unavailable.

PMID- 24735475
TI  - Cardenolides from the bark of Calotropis gigantea.
AB  - Three new cardenolides (1-3) were isolated from the 90% ethanolic extract of the
      bark of a wild-type Calotropis gigantea. Their structures were determined by
      using NMR spectra and LC-MS analysis. Their inhibitory activities were evaluated
      against non-small cell lung carcinoma (A549) and human cervix epithelial
      adenocarcinoma (HeLa) cell lines. Compounds 1 and 3 exhibited strong inhibitory
      effect on two cancer cell lines.

PMID- 24735476
TI  - Cool sperm: why some placental mammals have a scrotum.
AB  - Throughout the Cenozoic, the fitness benefits of the scrotum in placental mammals
      presumably outweighed the fitness costs through damage, yet a definitive
      hypothesis for its evolution remains elusive. Here, I present an hypothesis
      (Endothermic Pulses Hypothesis) which argues that the evolution of the scrotum
      was driven by Cenozoic pulses in endothermy, that is, increases in normothermic
      body temperature, which occurred in Boreotheria (rodents, primates, lagomorphs,
      carnivores, bats, lipotyphylans and ungulates) in response to factors such as
      cursoriality and climate adaptation. The model argues that stabilizing selection
      maintained an optimum temperature for spermatogenesis and sperm storage
      throughout the Cenozoic at the lower plesiomorphic levels of body temperature
      that prevailed in ancestral mammals for at least 163 million years. Evolutionary
      stasis may have been driven by reduced rates of germ-cell mutations at lower body
      temperatures. Following the extinction of the dinosaurs at the Cretaceous
      Palaeogene boundary 65.5 mya, immediate pulses in endothermy occurred associated
      with the dramatic radiation of the modern placental mammal orders. The fitness
      advantages of an optimum temperature of spermatogenesis outweighed the potential
      costs of testes externalization and paved the way for the evolution of the
      scrotum. The scrotum evolved within several hundred thousand years of the K-Pg
      extinction, probably associated initially with the evolution of cursoriality, and
      arguably facilitated mid- and late Cenozoic metabolic adaptations to factors such
      as climate, flight in bats and sociality in primates. 

PMID- 24735477
TI  - Flexible three-dimensional nanoporous metal-based energy devices.
AB  - A flexible three-dimensional (3-D) nanoporous NiF2-dominant layer on
      poly(ethylene terephthalate) has been developed. The nanoporous layer itself can
      be freestanding without adding any supporting carbon materials or conducting
      polymers. By assembling the nanoporous layer into two-electrode symmetric
      devices, the inorganic material delivers battery-like thin-film supercapacitive
      performance with a maximum capacitance of 66 mF cm(-2) (733 F cm(-3) or 358 F g(
      1)), energy density of 384 Wh kg(-1), and power density of 112 kW kg(-1).
      Flexibility and cyclability tests show that the nanoporous layer maintains its
      high performance under long-term cycling and different bending conditions. The
      fabrication of the 3-D nanoporous NiF2 flexible electrode could be easily scaled.

PMID- 24735479
TI  - Role of AMACR (alpha-methylacyl-CoA racemase) and MFE-1 (peroxisomal
      multifunctional enzyme-1) in bile acid synthesis in mice.
AB  - Cholesterol is catabolized to bile acids by peroxisomal beta-oxidation in which
      the side chain of C27-bile acid intermediates is shortened by three carbon atoms
      to form mature C24-bile acids. Knockout mouse models deficient in AMACR (alpha
      methylacyl-CoA racemase) or MFE-2 (peroxisomal multifunctional enzyme type 2), in
      which this beta-oxidation pathway is prevented, display a residual C24-bile acid
      pool which, although greatly reduced, implies the existence of alternative
      pathways of bile acid synthesis. One alternative pathway could involve Mfe-1
      (peroxisomal multifunctional enzyme type 1) either with or without Amacr. To test
      this hypothesis, we generated a double knockout mouse model lacking both Amacr
      and Mfe-1 activities and studied the bile acid profiles in wild-type, Mfe-1 and
      Amacr single knockout mouse line and Mfe-1 and Amacr double knockout mouse lines.
      The total bile acid pool was decreased in Mfe-1-/- mice compared with wild-type
      and the levels of mature C24-bile acids were reduced in the double knockout mice
      when compared with Amacr-deficient mice. These results indicate that Mfe-1 can
      contribute to the synthesis of mature bile acids in both Amacr-dependent and
      Amacr-independent pathways. 

PMID- 24735478
TI  - Signaling by epithelial members of the CEACAM family - mucosal docking sites for
      pathogenic bacteria.
AB  - Carcinoembryonic antigen-related cell adhesion molecules (CEACAMs) comprise a
      group of immunoglobulin-related vertebrate glycoproteins. Several family members,
      including CEACAM1, CEA, and CEACAM6, are found on epithelial tissues throughout
      the human body. As they modulate diverse cellular functions, their signaling
      capacity is in the focus of current research. In this review we will summarize
      the knowledge about common signaling processes initiated by epithelial CEACAMs
      and suggest a model of signal transduction by CEACAM family members lacking
      significant cytoplasmic domains. As pathogenic and non-pathogenic bacteria
      exploit these receptors during mucosal colonization, we try to highlight the
      connection between CEACAMs, microbes, and cellular responses. Special emphasis in
      this context is placed on the functional interplay between CEACAMs and integrins
      that influences matrix adhesion of epithelial cells. The cooperation between
      these two receptor families provides an intriguing example of the fine tuning of
      cellular responses and their manipulation by specialized microorganisms. 

PMID- 24735480
TI  - Clinical study on survival rate of short implants placed in the posterior
      mandibular region: resonance frequency analysis.
AB  - OBJECTIVE: Short implants are increasingly used, but there is doubt about their
      performance being similar to that of regular implants. The aim of this study was
      to compare the mechanical stability of short implants vs. regular implants placed
      in the edentulous posterior mandible. MATERIAL AND METHODS: Twenty-three patients
      received a total of 48 short implants (5 * 5.5 mm and 5 * 7 mm) and 42 regular
      implants (4 * 10 mm and 4 * 11.5 mm) in the posterior mandible. Patients who
      received short implants had <10 mm of bone height measured from the bone crest to
      the outer wall of the mandibular canal. Resonance frequency analysis (RFA) was
      performed at time intervals T0 (immediately after implant placement), T1 (after
      15 days), T2 (after 30 days), T3 (after 60 days), and T4 (after 90 days).
      RESULTS: The survival rate after 90 days was 87.5% for the short implants and
      100% for regular implants (P < 0.05). There was no significant difference between
      the implants in time intervals T1, T2, T3, and T4. In T0, the RFA values of 5 *
      5.5 implants were higher than values of 5 * 7 and 4 * 11.5 implants (P < 0.05). A
      total of six short implants that were placed in four patients were lost (three of
      5 * 5.5 mm and three of 5 * 7 mm). Three lost implants started with high ISQ
      values, which progressively decreased. The other three lost implants started with
      a slightly lower ISQ value, which rose and then began to fall. CONCLUSIONS:
      Survival rate of short implants after 90 days was lower than that of regular
      implants. However, short implants may be considered a reasonable alternative for
      rehabilitation of severely resorbed mandibles with reduced height, to avoid
      performing bone reconstruction before implant placement. Patients need to be
      aware of the reduced survival rate compared with regular implants before implant
      placement to avoid disappointments.

PMID- 24735482
TI  - Primary prevention implantable cardioverter-defibrillator implantation in elderly
      patients: is it justified to withhold treatment?
AB  - Implementation of primary prevention implantable cardioverter-defibrillator (ICD)
      treatment in the current clinical guidelines led to a significant increase in
      patients that may benefit from implantation of an ICD. Currently non-guideline
      guided patient selection takes place by physicians whereby patients at higher age
      are more frequently excluded for ICD implantation. This editorial focuses on ICD
      treatment in the elderly and aims to clarify whether it is justified to withhold
      ICD treatment in these patients. 

PMID- 24735481
TI  - Epicutaneously applied Der p 2 induces a strong TH 2-biased antibody response in
      C57BL/6 mice, independent of functional TLR4.
AB  - BACKGROUND: The major house dust mite allergen Der p 2 is a structural and
      functional homologue of MD-2 within the TLR4-CD14-MD-2 complex. An asthma mouse
      model in TLR4-deficient mice recently suggested that the allergic immune response
      against Der p 2 is solely dependent on TLR4 signaling. We investigated whether
      similar mechanisms are important for Der p 2 sensitization via the skin. METHODS:
      In an epicutaneous sensitization model, the response to recombinant Der p 2 in
      combination with or without lipopolysaccharide (LPS) was compared between C57BL/6
      WT and TLR4-deficient mice. We further analyzed possible adjuvant function of
      exogenous cysteine proteases. RESULTS: Sensitization with rDer p 2 induced
      similar levels of allergen-specific IgG1 and IgE antibodies in both mouse
      strains. LPS increased the systemic (antibody levels, cytokine release by
      restimulated splenocytes) and local (infiltration of immune cells into the skin)
      Th2 immune responses, which against our expectations were stronger in the absence
      of functional TLR4 expression. Barrier disruption by papain, a protease with
      structural homology to Der p 1, did not enhance the sensitization capacity of
      rDer p 2. However, the presence of LPS increased the stability of rDer p 2
      against the protease. CONCLUSION: Our data suggest that rDer p 2 alone can cause
      a strong TH 2-biased response via the skin being enhanced in the presence of LPS.
      This response is not reliant on functional TLR4, but vice versa TLR4 expression
      rather protects against epicutaneous sensitization to house dust mite allergen
      Der p 2.

PMID- 24735484
TI  - Lipids as universal biomarkers of extraterrestrial life.
AB  - In 1965, James Lovelock published a general statement, based on thermodynamic
      chemical equilibrium principles, about how to detect extant or extinct life on a
      planet other than Earth. Nearly 50 years later, it is possible to make such
      measurements with robotic missions such as current and future Mars rovers, and
      probes to sample icy plumes of Enceladus or Europa. We make a specific
      recommendation that certain characteristic patterns in the composition of lipid
      hydrocarbons can only result from a biological process, because the signal arises
      from a universal requirement related to lipid bilayer fluidity and membrane
      stability. Furthermore, the pattern can be preserved over millions of years, and
      instrumentation is already available to be incorporated into flight missions.

PMID- 24735483
TI  - Layer-specific gene expression in epileptogenic type II focal cortical dysplasia:
      normal-looking neurons reveal the presence of a hidden laminar organization.
AB  - BACKGROUND: Type II focal cortical dysplasias (FCDs) are malformations of
      cortical development characterised by the disorganisation of the normal
      neocortical structure and the presence of dysmorphic neurons (DNs) and balloon
      cells (BCs). The pathogenesis of FCDs has not yet been clearly established,
      although a number of histopathological patterns and molecular findings suggest
      that they may be due to abnormal neuronal and glial proliferation and migration
      processes.In order to gain further insights into cortical layering disruption and
      investigate the origin of DNs and BCs, we used in situ RNA hybridisation of human
      surgical specimens with a neuropathologically definite diagnosis of Type IIa/b
      FCD and a panel of layer-specific genes (LSGs) whose expression covers all
      cortical layers. We also used anti-phospho-S6 ribosomal protein antibody to
      investigate mTOR pathway hyperactivation. RESULTS: LSGs were expressed in both
      normal and abnormal cells (BCs and DNs) but their distribution was different.
      Normal-looking neurons, which were visibly reduced in the core of the lesion,
      were apparently located in the appropriate cortical laminae thus indicating a
      partial laminar organisation. On the contrary, DNs and BCs, labelled with anti
      phospho-S6 ribosomal protein antibody, were spread throughout the cortex without
      any apparent rule and showed a highly variable LSG expression pattern. Moreover,
      LSGs did not reveal any differences between Type IIa and IIb FCD. CONCLUSION:
      These findings suggest the existence of hidden cortical lamination involving
      normal-looking neurons, which retain their ability to migrate correctly in the
      cortex, unlike DNs which, in addition to their morphological abnormalities and
      mTOR hyperactivation, show an altered migratory pattern.Taken together these data
      suggest that an external or environmental hit affecting selected precursor cells
      during the very early stages of cortical development may disrupt normal cortical
      development.

PMID- 24735485
TI  - Accuracy of the lamellar body count in amniotic fluid contaminated by meconium.
AB  - OBJECTIVE: To determine whether meconium-contaminated amniotic fluid falsely
      elevates the lamellar body count in fetal lung maturity testing. METHODS: Thirty
      mothers undergoing amniocentesis for fetal lung maturity testing were
      prospectively consented. A 2 mL portion of the patient's sample was mixed with a
      10% meconium solution and the meconium-stained sample was then run in tandem with
      the patient's sample used in clinical management. Pure meconium samples without
      amniotic fluid were also run through the cell counter for analysis. RESULTS:
      Following meconium contamination, the lamellar body count value increased in 67%
      of the cases, decreased in 23% and remained the same in 10%. There were 13 test
      results that had "immature" values in the uncontaminated patient management
      sample group and nine of these (69%) became elevated to a "mature" level (a false
      elevation) following the addition of meconium. All of the 10 pure liquid meconium
      samples devoid of amniotic fluid processed by the cell counter identified and
      quantified some particle the size of platelets. CONCLUSIONS: The lamellar body
      count test result is not reliable in meconium-stained amniotic fluid specimens.
      There is some unknown particle found in meconium that is the size of
      platelets/lamellar bodies that can falsely elevate the test result. Currently,
      the only reliable fetal lung maturity test in meconium-stained amniotic fluid is
      the presence of phosphatidylglycerol.

PMID- 24735486
TI  - Prenatal diagnosis of amniotic band syndrome - risk factors and ultrasonic signs.
AB  - OBJECTIVE: The aim of this study was to describe our experience with amniotic
      band syndrome (ABS), define specific sonographic characteristics and common
      features. METHODS: Patients diagnosed with ABS underwent detailed ultrasound
      evaluation at the time of diagnosis and during follow-up. Their ultrasound
      examinations and medical records concerning the current pregnancy and past
      medical records were analyzed. RESULTS: Ten pregnancies were diagnosed with ABS.
      Most pregnancies were diagnosed at the beginning of the second trimester. Two
      cases were bichorionic twin pregnancies involving one of the fetuses and these
      were the only women who continued their pregnancies to term. The other eight
      cases with ABS chose to terminate their pregnancies. One pregnancy was conceived
      following trachelectomy. We found a significantly higher rate of prior uterine
      surgeries (p = 0.008) in patient with ABS compared to control. In three cases,
      all above 15 weeks of gestation, a small vestige at the distal part of the
      amputated limb was observed. CONCLUSIONS: ABS diagnosed in early pregnancy can be
      a sporadic event. However, there is a higher risk of ABS in pregnancies preceded
      by uterine procedures. The ultrasonic vestige sign at the amputated limb may
      contribute to the diagnosis of ABS.

PMID- 24735487
TI  - Outcome of pregnancy with history-indicated cervical cerclage insertion in a low
      resource setting.
AB  - OBJECTIVE: History-indicated cervical cerclage insertion is required when factors
      in a woman's history could predispose to spontaneous miscarriage or preterm
      birth. This retrospective study determined the pregnancy outcome after insertion
      of history-indicated cervical cerclage for at least one previous mid-trimester
      spontaneous abortion over a 10-year period in a low-resource setting. METHODS:
      This was a retrospective analysis of hospital data. Data was retrieved on
      biosocial and obstetrics parameters and analysed. The outcome measures were
      recurrence of spontaneous miscarriage, preterm delivery rate and fetal salvage
      rate. Descriptive frequencies were used to present results. The test of
      statistical significance was with Yates' coefficient correlation at 95%
      confidence interval. RESULTS: Cervical cerclage rate was 7 per 1000 births.
      Diagnosis was clinical and cerclage was inserted at a mean gestational age of 15
      +/- 3.6 weeks. Hospital admission greater than five days after cerclage insertion
      had no statistically significant difference on preterm delivery (CI 95%; p value
      = 0.98). Repeat spontaneous miscarriage occurred less (5.6%) after cerclage
      insertion, fetal salvage rate was 75% and the preterm birth rate was 30%.
      CONCLUSION: The limitations of the study notwithstanding, use of history
      indicated cervical cerclage in pregnancy resulted in better fetal salvage rate
      and reduced recurrence of spontaneous miscarriage.

PMID- 24735489
TI  - Psychosocial well-being in young adults with chronic illness since childhood: the
      role of illness cognitions.
AB  - BACKGROUND: More and more pediatric patients reach adulthood. Some of them are
      successfully integrating in adult life, but many others are not. Possibly Illness
      cognitions (IC) - the way people give meaning to their illness/disability - may
      play a role in individual differences on long-term adjustment. This study
      explored the association of IC with disease-characteristics and Health Related
      Quality of Life (HRQoL), anxiety and depression in young adults with a disability
      benefit due to childhood-onset chronic condition. METHODS: In a cross-sectional
      study, young adults (22-31 years, N = 377) who claimed a disability benefit
      because of a somatic condition since childhood, completed the Illness Cognition
      Questionnaire (acceptance-helplessness-benefits), RAND-36 (HRQoL) and HADS
      (anxiety and depression) online. Besides descriptive statistics, linear
      regression analyses were conducted to predict (1) illness cognitions by age,
      gender and disease-characteristics, and (2) HRQoL (Mental and Physical Component
      Scale), Anxiety and Depression by illness cognitions, controlling for disease
      characteristics, age and gender. RESULTS: Respectively 90.2%, 83.8% and 53.3% of
      the young adults with a disability benefit experienced feelings of acceptance,
      benefits and helplessness. Several disease-characteristics were associated with
      IC. More acceptance and less helplessness were associated with better mental
      (beta = 0.31; beta = -0.32) and physical (beta = 0.16; beta = -0.15) HRQoL and
      with less anxiety (beta = -0.27; beta = 0.28) and depression (beta = -0.29; beta
      = 0.31). CONCLUSIONS: IC of young adult beneficiaries were associated with their
      HRQoL and feelings of anxiety and depression. Early recognition of psychological
      distress and negative IC might be a key to the identification of pediatric
      patients at risk for long-term dysfunction. Identification of maladaptive illness
      cognitions enables the development of psychosocial interventions to optimise
      their well-being and adaptation to society.

PMID- 24735490
TI  - Genetic variants in or near ADH1B and ADH1C affect susceptibility to alcohol
      dependence in a British and Irish population.
AB  - Certain single nucleotide polymorphisms (SNPs) in genes encoding alcohol
      dehydrogenase (ADH) enzymes confer a significant protective effect against
      alcohol dependence syndrome (ADS) in East Asian populations. Recently, attention
      has focused on the role of these SNPs in determining ADS risk in European
      populations. To further elucidate these associations, SNPs of interest in ADH1B,
      ADH1C and the ADH1B/1C intergenic region were genotyped in a British and Irish
      population (ADS cases n = 1076: controls n = 1027) to assess their relative
      contribution to ADS risk. A highly significant, protective association was
      observed between the minor allele of rs1229984 in ADH1B and ADS risk [allelic P =
      8.4 * 10(-6) , odds ratio (OR) = 0.26, 95 percent confidence interval, 0.14,
      0.49]. Significant associations were also observed between ADS risk and the
      ADH1B/1C intergenic variant, rs1789891 [allelic P = 7.2 * 10(-5) , OR = 1.4 (1.2,
      1.6)] and three non-synonymous SNPs rs698, rs1693482 and rs283413 in ADH1C.
      However, these associations were not completely independent; thus, while the
      ADH1B rs1229984 minor allele association was independent of those of the
      intergenic variant rs1789891 and the three ADH1C variants, the three ADH1C
      variants were not individually independent. In conclusion, the rare ADH1B
      rs1229984 mutation provides significant protection against ADS in this British
      and Irish population; other variants in the ADH gene cluster also alter ADS risk,
      although the strong linkage disequilibrium between SNPs at this location
      precluded clear identification of the variant(s) driving the associations. 

PMID- 24735491
TI  - JNC 8 or too much of a good thing.

PMID- 24735493
TI  - In vitro investigation of the efficacy of novel diamidines against Trypanosoma
      cruzi.
AB  - Chagas' disease is a neglected tropical disease caused by Trypanosoma cruzi and
      constitutes a serious public health problem for Latin America. Its unsatisfactory
      chemotherapy stimulates the search for novel antiparasitic compounds. Amidines
      and related compounds exhibit well-known activity towards different microbes
      including T. cruzi. In this vein, our present aim was to evaluate the biological
      effect of 10 novel structurally related amidines in vitro against bloodstream and
      intracellular forms of the parasite as well as their potential toxicity on
      cardiac cell cultures. Our results show that although active against the
      extracellular forms, with some of them like DB2247 being 6-fold more effective
      than benznidazole and displaying very low toxicity (>96 MUm), none presented
      superior trypanocidal effect against intracellular forms as compared with the
      reference drug. These results may be due to differences in susceptibility
      profiles related to distinct uptake/extrusion mechanisms and cellular targets
      between bloodstream and amastigote forms. The present study adds to the knowledge
      base for the future design of novel amidines that may provide promising activity
      against T. cruzi.

PMID- 24735492
TI  - Design and synthesis of systemically active metabotropic glutamate subtype-2 and 
      3 (mGlu2/3) receptor positive allosteric modulators (PAMs): pharmacological
      characterization and assessment in a rat model of cocaine dependence.
AB  - As part of our ongoing small-molecule metabotropic glutamate (mGlu) receptor
      positive allosteric modulator (PAM) research, we performed structure-activity
      relationship (SAR) studies around a series of group II mGlu PAMs. Initial
      analogues exhibited weak activity as mGlu2 receptor PAMs and no activity at
      mGlu3. Compound optimization led to the identification of potent mGlu2/3
      selective PAMs with no in vitro activity at mGlu1,4-8 or 45 other CNS receptors.
      In vitro pharmacological characterization of representative compound 44 indicated
      agonist-PAM activity toward mGlu2 and PAM activity at mGlu3. The most potent
      mGlu2/3 PAMs were characterized in assays predictive of ADME/T and
      pharmacokinetic (PK) properties, allowing the discovery of systemically active
      mGlu2/3 PAMs. On the basis of its overall profile, compound 74 was selected for
      behavioral studies and was shown to dose-dependently decrease cocaine self
      administration in rats after intraperitoneal administration. These mGlu2/3
      receptor PAMs have significant potential as small molecule tools for
      investigating group II mGlu pharmacology. 

PMID- 24735494
TI  - Derivation of optical properties of carbonaceous aerosols by monochromated
      electron energy-loss spectroscopy.
AB  - Monochromated electron energy-loss spectroscopy (EELS) is employed to determine
      the optical properties of carbonaceous aerosols from the infrared to the
      ultraviolet region of the spectrum. It is essential to determine their optical
      properties to understand their accurate contribution to radiative forcing for
      climate change. The influence of surface and interface plasmon effects on the
      accuracy of dielectric data determined from EELS is discussed. Our measurements
      show that the standard thin film formulation of Kramers-Kronig analysis can be
      employed to make accurate determination of the dielectric function for
      carbonaceous particles down to about 40 nm in size. The complex refractive
      indices of graphitic and amorphous carbon spherules found in the atmosphere were
      determined over the wavelength range 200-1,200 nm. The graphitic carbon was
      strongly absorbing black carbon, whereas the amorphous carbon shows a more weakly
      absorbing brown carbon profile. The EELS approach provides an important tool for
      exploring the variation in optical properties of atmospheric carbon. 

PMID- 24735495
TI  - Socioeconomic and demographic factors modify the association between informal
      caregiving and health in the Sandwich Generation.
AB  - BACKGROUND: Nearly 50 million Americans provide informal care to an older
      relative or friend. Many are members of the "sandwich generation", providing care
      for elderly parents and children simultaneously. Although evidence suggests that
      the negative health consequences of caregiving are more severe for sandwiched
      caregivers, little is known about how these associations vary by sociodemographic
      factors. METHODS: We abstracted data from the Behavioral Risk Factor Surveillance
      System to determine how the association between caregiving and health varies by
      sociodemographic factors, using ordinal logistic regression with interaction
      terms and stratification by number of children, income, and race/ethnicity.
      RESULTS: The association between informal caregiving and health varied by
      membership in the "sandwich generation," income, and race/ethnicity. This
      association was significant among subjects with one (OR=1.13, 95% CI [1.04,
      1.24]) and two or more children (OR=1.17, 95% CI=1.09, 1.26]), but not in those
      without children (OR=1.01, 95% CI [0.97, 1.05]). Associations were strongest in
      those earning $50,000-$75,000 annually, but these income-dependent associations
      varied by race/ethnicity. In Whites with two or more children, the strongest
      associations between caregiving and health occurred in lower income individuals.
      These trends were not observed for Whites without children. CONCLUSIONS: Our
      findings suggest that the added burden of caregiving for both children and
      elderly relatives may be impacted by income and race/ethnicity. These differences
      should be considered when developing culturally appropriate interventions to
      improve caregiver health and maintain this vital component of the US health care
      system.

PMID- 24735496
TI  - Direct observation of nanoscale Peltier and Joule effects at metal-insulator
      domain walls in vanadium dioxide nanobeams.
AB  - The metal to insulator transition (MIT) of strongly correlated materials is
      subject to strong lattice coupling, which brings about the unique one-dimensional
      alignment of metal-insulator (M-I) domains along nanowires or nanobeams. Many
      studies have investigated the effects of stress on the MIT and hence the phase
      boundary, but few have directly examined the temperature profile across the metal
      insulating interface. Here, we use thermoreflectance microscopy to create two
      dimensional temperature maps of single-crystalline VO2 nanobeams under external
      bias in the phase coexisting regime. We directly observe highly localized
      alternating Peltier heating and cooling as well as Joule heating concentrated at
      the M-I domain boundaries, indicating the significance of the domain walls and
      band offsets. Utilizing the thermoreflectance technique, we are able to elucidate
      strain accumulation along the nanobeam and distinguish between two insulating
      phases of VO2 through detection of the opposite polarity of their respective
      thermoreflectance coefficients. Microelasticity theory was employed to predict
      favorable domain wall configurations, confirming the monoclinic phase
      identification. 

PMID- 24735497
TI  - Identification of two novel HLA-A*24 alleles, HLA-A*24:02:69 and HLA-A*24:247 by
      cloning and sequencing.

PMID- 24735499
TI  - Examining the role of parental self-regulation in family physical activity: a
      mixed-methods approach.
AB  - Physical activity (PA) is essential for good health. However, parents risk
      becoming less active because of the demands of parenting. This has consequences
      for children as parents are role models. The present study used a mixed-methods
      approach to explore parental self-regulation associated with PA. Data were
      collected from 36 parents with preschool-aged children. They were interviewed
      about their PA and their family's PA. Parents also completed PA and self
      regulation questionnaires and wore an accelerometer for five days. Qualitative
      data were examined using an inductive approach to thematic analysis. It showed
      that parents felt that they had limited time for personal PA. Mothers' self
      regulation was driven by an ethic of care and subjective norms, whereas fathers'
      self-regulation was driven by beliefs about the importance of autonomy.
      Nevertheless, both parents saw caring for their children as the main priority.
      Quantitative data were examined using multiple regression analyses. Results
      showed that different self-regulatory behaviours predicted the PA of mothers and
      fathers. Which predictors were significant depended on the type of activity and
      how it was measured. The findings warrant longitudinal research that would enable
      the effect of family dynamics on self-regulation associated with PA to be
      assessed. 

PMID- 24735498
TI  - Cross-presentation of viral antigens in dribbles leads to efficient activation of
      virus-specific human memory T cells.
AB  - BACKGROUND: Autophagy regulates innate and adaptive immune responses to pathogens
      and tumors. We have reported that autophagosomes derived from tumor cells after
      proteasome inhibition, DRibbles (Defective ribosomal products in blebs), were
      excellent sources of antigens for efficient cross priming of tumor-specific CD8+
      T cells, which mediated regression of established tumors in mice. But the
      activity of DRibbles in human has not been reported. METHODS: DRibbles or cell
      lysates derived from HEK293T or UbiLT3 cell lines expressing cytomegalovirus
      (CMV) pp65 protein or transfected with a plasmid encoding dominant HLA-A2
      restricted CMV, Epstein-Barr virus (EBV), and Influenza (Flu) epitopes (CEF) were
      loaded onto human monocytes or PBMCs and the response of human CMV pp65 or CEF
      antigen-specific CD4+ and CD8+ memory T cells was detected by intracellular
      staining. The effect of cytokines (GM-CSF, IL-4, IL-12, TNF-alpha, IFN-alpha and
      IFN-gamma) TLR agonists (Lipopolysaccharide, Polyinosinic-polycytidylic acid
      (poly(I:C), M52-CpG, R848, TLR2 ligand) and CD40 ligand on the cross-presentation
      of antigens contained in DRibbles or cell lysates was explored. RESULTS: In this
      study we showed that purified monocytes, or human PBMCs, loaded with DRibbles
      isolated from cells expressing CMV or CEF epitopes, could activate CMV- or CEF
      specific memory T cells. DRibbles were significantly more efficient at
      stimulating CD8+ memory T cells compared to cell lysates expressing the same
      antigenic epitopes. We optimized the conditions for T-cell activation and IFN
      gamma production following direct loading of DRibbles onto PBMCs. We found that
      the addition of Poly(I:C), CD40 ligand, and GM-CSF to the PBMCs together with
      DRibbles significantly increased the level of CD8+ T cell responses. CONCLUSIONS:
      DRibbles containing specific viral antigens are an efficient ex vivo activator of
      human antigen-specific memory T cells specific for those antigens. This function
      could be enhanced by combining with Poly(I:C), CD40 ligand, and GM-CSF. This
      study provides proof-of-concept for applying this strategy to activate memory T
      cells against other antigens, including tumor-specific T cells ex vivo for
      immunological monitoring and adoptive immunotherapy, and in vivo as vaccines for
      patients with cancer.

PMID- 24735500
TI  - Within-field spatial distribution of stink bug (Hemiptera: Pentatomidae)-induced
      boll injury in commercial cotton fields of the southeastern United States.
AB  - Spatial distribution of boll injury caused by stink bugs to developing cotton
      (Gossypium hirsutum L.) bolls was studied in five commercial fields (?22 ha each)
      in 2011 and 2012 to understand variability in boll injury dynamics within fields.
      Cotton bolls and stink bugs were sampled weekly from a georeferenced grid of
      sampling points (one sample per 0.40 ha) in each field, but no samples were taken
      within 30 m of field edges. The inverse distance weighted interpolation,
      variogram analysis, and Moran's I were used to describe spatial variability of
      boll damage within the fields. Boll injury was found to be spatially associated
      at distances ranging from ?75 to 275 m with an average distance ?150 m. An
      exponential variogram model was selected as the best fitting model to describe
      the spatial association in four of the five fields. Moran's I indicated that
      spatial association was significant in three of the five fields. The spread of
      boll injury from stink bugs was gradual in most fields and always exceeded the
      treatment threshold during the fourth or fifth week of bloom. Capture of stink
      bugs using a sweep net was inefficient, strongly suggesting that quantifying boll
      injury is a better sampling method and predictor of stink bug activity when
      sampling all but the edges of the field. These data suggest that scouts need to
      sample boll injury from sample locations separated by at least 150 m to assure
      independence in the central part of large fields. Second, future researchers who
      plan to use parametric statistical methods could use a 150-m grid, as opposed to
      a denser grid that would require greater time and effort. 

PMID- 24735502
TI  - Evaluation of the implication of KIR2DL2 receptor in multiple sclerosis and
      herpesvirus susceptibility.
AB  - To evaluate the possible effect of cell immunoglobulin-like receptors (KIRs) on
      viral infection in multiple sclerosis (MS) patients, we performed genotyping of
      KIR2DL2 and his HLA-C1 ligand and we analyzed the presence of all eight human
      herpesviruses (HHVs) in 60 MS patients and 112 healthy controls. Significantly
      higher frequencies were found for KIR2DL2 enhanced in the presence of its ligand
      HLA-C1 in MS patients. Moreover, a significant association was observed between
      an increase in HHV risk of infection in KIR2DL2 and HLA-C1 positive patient. Our
      results confirm a possible effect of KIR2DL2 on viral infection susceptibility in
      MS patients. 

PMID- 24735501
TI  - Influence of pH on extracellular matrix preservation during lung
      decellularization.
AB  - The creation of decellularized organs for use in regenerative medicine requires
      the preservation of the organ extracellular matrix (ECM) as a means to provide
      critical cues for differentiation and migration of cells that are seeded onto the
      organ scaffold. The purpose of this study was to assess the influence of varying
      pH levels on the preservation of key ECM components during the decellularization
      of rat lungs. Herein, we show that the pH of the 3-[(3
      cholamidopropyl)dimethylammonio]-1-propanesulfonate (CHAPS)-based
      decellularization solution influences ECM retention, cell removal, and also the
      potential for host response upon implantation of acellular lung tissue. The
      preservation of ECM components, including elastin, fibronectin, and laminin, were
      better retained in the lower pH conditions that were tested (pH ranges tested: 8,
      10, 12); glycosaminoglycans were preserved to a higher extent in the lower pH
      groups as well. The DNA content following decellularization of the rat lung was
      inversely correlated with the pH of the decellularization solution. Despite
      detectible levels of cyotoskeletal proteins and significant residual DNA, tissues
      decellularized at pH 8 demonstrated the greatest tissue architecture maintenance
      and the least induction of host response of all acellular conditions. These
      results highlight the effect of pH on the results obtained by organ
      decellularization and suggest that altering the pH of the solutions used for
      decellularization may influence the ability of cells to properly differentiate
      and home to appropriate locations within the scaffold, based on the preservation
      of key ECM components and implantation results. 

PMID- 24735503
TI  - The effect of patient positioning on the precision of model-based
      radiostereometric analysis.
AB  - A repeatable method for in vivo and in vitro measurement of polyethylene wear in
      total knee replacement (TKA) is needed. This research examines the model-based
      radiostereometric analysis' (MBRSA) in vitro precision under different patient
      radiograph orientations and flexion angles of the knee using a TKA phantom.
      Anterior-posterior and medial-lateral imaging orientations showed the highest
      precision; better than 0.036mm (3-dimensional translation) and 0.089 degrees  (3
      dimensional rotation). Flexion of the knee did not affect MBRSA precision. Medial
      lateral imaging is advantageous as it allows for flexion of the knee joint during
      an RSA examination, thus providing greater information for wear measurement. 

PMID- 24735504
TI  - Creation of an in vitro biomechanical model of the trachea using rapid
      prototyping.
AB  - Previous in vitro models of the airways are either rigid or, if flexible, have
      not matched in vivo compliance characteristics. Rapid prototyping provides a
      quickly evolving approach that can be used to directly produce in vitro airway
      models using either rigid or flexible polymers. The objective of this study was
      to use rapid prototyping to directly produce a flexible hollow model that matches
      the biomechanical compliance of the trachea. The airway model consisted of a
      previously developed characteristic mouth-throat region, the trachea, and a
      portion of the main bronchi. Compliance of the tracheal region was known from a
      previous in vivo imaging study that reported cross-sectional areas over a range
      of internal pressures. The compliance of the tracheal region was matched to the
      in vivo data for a specific flexible resin by iteratively selecting the
      thicknesses and other dimensions of tracheal wall components. Seven iterative
      models were produced and illustrated highly non-linear expansion consisting of
      initial rapid size increase, a transition region, and continued slower size
      increase as pressure was increased. Thickness of the esophageal interface
      membrane and initial trachea indention were identified as key parameters with the
      final model correctly predicting all phases of expansion within a value of 5% of
      the in vivo data. Applications of the current biomechanical model are related to
      endotracheal intubation and include determination of effective mucus suctioning
      and evaluation of cuff sealing with respect to gases and secretions. 

PMID- 24735505
TI  - Transference of 3D accelerations during cross country mountain biking.
AB  - Investigations into the work demands of Olympic format cross country mountain
      biking suggest an incongruent relationship between work done and physiological
      strain experienced by participants. A likely but unsubstantiated cause is the
      extra work demand of muscle damping of terrain/surface induced vibrations. The
      purpose of this study was to describe the relationship between vibration
      mechanics and their interaction with terrain, bicycle and rider during a race
      pace effort on a cross country mountain bike track, on both 26" and 29" wheels.
      Participants completed one lap of a cross country track using 26" and 29" wheels,
      at race pace. Power, cadence, speed, heart rate and geographical position were
      sampled and logged every second for control purposes. Tri-axial accelerometers
      located on the bicycle and rider, recorded accelerations (128Hz) and were used to
      quantify vibrations experienced during the whole lap and over terrain sections
      (uphill and downhill). While there were no differences in power output (p=0.3062)
      and heart rate (p=0.8423), time to complete the lap was significantly (p=0.0061)
      faster on the 29" wheels despite increased vibrations in the larger wheels
      (p=0.0020). Overall accelerometer data (RMS) showed location differences
      (p<0.0001), specifically between the point of interface of bike-body compared to
      those experienced at the lower back and head. The reduction in accelerations at
      both the lower back and head are imperative for injury prevention and
      demonstrates an additional non-propulsive, muscular, challenge to riding. Stress
      was greatest during downhill sections as acceleration differences between
      locations were greater when compared to uphill sections, and thus possibly
      prevent the recovery processes that may occur during non-propulsive load. 

PMID- 24735506
TI  - A new geometric-based model to accurately estimate arm and leg inertial
      estimates.
AB  - Segment estimates of mass, center of mass and moment of inertia are required
      input parameters to analyze the forces and moments acting across the joints. The
      objectives of this study were to propose a new geometric model for limb segments,
      to evaluate it against criterion values obtained from DXA, and to compare its
      performance to five other popular models. Twenty five female and 24 male college
      students participated in the study. For the criterion measures, the participants
      underwent a whole body DXA scan, and estimates for segment mass, center of mass
      location, and moment of inertia (frontal plane) were directly computed from the
      DXA mass units. For the new model, the volume was determined from two standing
      frontal and sagittal photographs. Each segment was modeled as a stack of slices,
      the sections of which were ellipses if they are not adjoining another segment and
      sectioned ellipses if they were adjoining another segment (e.g. upper arm and
      trunk). Length of axes of the ellipses was obtained from the photographs. In
      addition, a sex-specific, non-uniform density function was developed for each
      segment. A series of anthropometric measurements were also taken by directly
      following the definitions provided of the different body segment models tested,
      and the same parameters determined for each model. Comparison of models showed
      that estimates from the new model were consistently closer to the DXA criterion
      than those from the other models, with an error of less than 5% for mass and
      moment of inertia and less than about 6% for center of mass location. 

PMID- 24735507
TI  - Current status of the field of obesity.
AB  - Obesity is a new specialty of medicine fighting for recognition. Current
      treatments with diet, exercise, and lifestyle modification have a high failure
      rate. Few obesity drugs exist and they are not very effective. Research should
      focus on understanding basic mechanisms, the numerous etiologies of obesity, and
      new drug development. Understanding the mechanisms of bariatric surgery, which
      does work, will lead to new drugs and better treatment. 

PMID- 24735509
TI  - Pride in not being prejudiced.

PMID- 24735508
TI  - Individual, facility, and program factors affecting retention in a national
      weight management program.
AB  - BACKGROUND: High attrition is a common problem for weight loss programs and
      directly affects program effectiveness. Since 2006, the Veterans Health
      Administration (VHA) has offered obesity treatment to its beneficiaries through
      the MOVE! Weight Management Program for Veterans (MOVE!). An early evaluation of
      this program showed that attrition rate was high. The present study examines how
      individual, facility, and program factors relate to retention for participants in
      the on-site MOVE! group program. METHODS: Data for all visits to MOVE! group
      treatment sessions were extracted from the VHA outpatient database. Participants
      were classified into three groups by their frequency of visits to the group
      program during a six month period after enrollment: early dropouts (1 - 3
      visits), late dropouts (4 - 5 visits), and completers (6 or more visits). A
      generalized ordered logit model was used to examine individual, facility, and
      program factors associated with retention. RESULTS: More than 60% of participants
      were early dropouts and 11% were late dropouts. Factors associated with retention
      were older age, presence of one or more comorbidities, higher body mass index at
      baseline, lack of co-payment requirement, geographic proximity to VA facility,
      addition of individual consultation to group treatment, greater program staffing,
      and regular, on-site physical activity programming. A non-completion rate of 74%
      for on-site group obesity treatment poses a major challenge to reducing the
      population prevalence of obesity within the VHA. CONCLUSIONS: Greater attention
      to individualized consultation, accessibility to the program, and facility
      factors including staffing and physical activity resources may improve retention.

PMID- 24735514
TI  - Recurrent convulsion with curious hair and skin changes in a 7-month-old. Menkes
      kinky hair syndrome.

PMID- 24735515
TI  - Australian evidence-based website: Raising Children Network.

PMID- 24735516
TI  - Cross-border promotion of formula milk.

PMID- 24735517
TI  - Cerebral venous thrombosis masquerading as pseudotumour cerebri in a paediatric
      patient.

PMID- 24735518
TI  - Is a life worth living?

PMID- 24735520
TI  - Interpretation of Neurally Adjusted Ventilatory Assist (NAVA) waveforms.

PMID- 24735521
TI  - Noninvasive ventilation in acute asthma.
AB  - Noninvasive ventilation (NIV) has well-recognized benefits in acute exacerbation
      of chronic obstructive pulmonary disease and pulmonary edema. Its utilization in
      acute asthma, however, remains controversial. In this review, we describe the
      physiological basis to justify NIV use in acute asthma and contribute a critical
      appraisal of the available literature relating to this practice. A discussion of
      some of the more pertinent, clinically relevant practicalities is also provided.
      Original research articles were identified using the electronic PubMed database.
      Randomized controlled trials of NIV in the setting of acute asthma were selected.
      Retrospective observational studies were also included if they were considered to
      contribute to the literature review. The use of NIV in the acute asthma setting
      has been shown to be associated with improvements in important physiological
      variables including measures of airflow and respiratory rate, and lends support
      to further study in this field. Improvements in airflow may be a direct effect of
      applied positive airway pressure or an indirect effect secondary to better
      dispersal of aerosolized medication. Reductions observed in respiratory rate and
      dyspnea are likely influenced by the amount of pressure support provided.
      Evidence suggestive of any improvement in mortality, intubation rate, or
      hospital/intensive care unit length of stay, however, is lacking. Studies to date
      have been hampered by small numbers and a lack of demonstrable meaningful
      clinical outcomes. Data relating to mortality, endotracheal intubation rates, and
      hospital length of stay/admission should be sought in future large clinical
      trials. 

PMID- 24735522
TI  - A spectroscopic rule from the solvatochromism of aromatic solutes in nonpolar
      solvents.
AB  - The UV-vis absorption spectroscopy for a series of selected symmetrical aromatic
      hydrocarbons, benzene, naphthalene, anthracene, 9,10-diphenylanthracene,
      perylene, and rubrene in the gas phase or in 2-methylbutane, shows the
      consistency of a new spectroscopic rule. From a thorough spectroscopic analysis
      with temperature variation (293-113 K) this rule states that "an aromatic
      molecule, on Franck-Condon excitation can hardly generate an excited electronic
      state with a lower polarizability than that of its ground electronic-state." We
      have not found any exceptions to this rule. 

PMID- 24735523
TI  - De novo 1Mb interstitial deletion of 8p22 in a patient with slight mental
      retardation and speech delay.
AB  - We report on a nine years old girl born after 41 weeks of normal gestation with
      psychomotor retardation, speech delay and minimal dysmorphic signs: antimongolic
      cut eyes, small mouth, short philtrum and hypertelorism. The use of the high
      resolution Affymetrix Human Mapping GeneChip 250 K NspI array allowed the
      characterization of a de novo 1Mb deletion on the short arm (p22) of a chromosome
      8. Molecular cytogenetic-FISH with BAC probes (RP11) confirmed the deletion. The
      deleted region includes part of the sarcoglycan zeta (SGCZ) gene, involved in the
      sarcoglycan complex formation, and the microRNA 383. The deletion described in
      our patient falls 319 Kb upstream of the Tumor Suppressor Candidate 3 (TUSC3)
      gene. In this chromosomal region, a limited number of cases of overlapping
      deletions, of variable extensions and characterized by heterogeneous clinical
      phenotype, have been reported. The deleted region described in our patient is the
      smallest among those so far described in this region. 

PMID- 24735524
TI  - Nation related participation and performance trends in 'Ironman Hawaii' from 1985
      to 2012.
AB  - BACKGROUND: This study examined participation and performance trends in 'Ironman
      Hawaii' regarding the nationality of the finishers. METHODS: Associations between
      nationalities and race times of 39,706 finishers originating from 124 countries
      in the 'Ironman Hawaii' from 1985 to 2012 were analyzed using single and multi
      level regression analysis. RESULTS: Most of the finishers originated from the
      United States of America (47.5%) followed by athletes from Germany (11.7%), Japan
      (7.9%), Australia (6.7%), Canada (5.2%), Switzerland (2.9%), France (2.3%), Great
      Britain (2.0%), New Zealand (1.9%), and Austria (1.5%). German women showed the
      fastest increase in finishers (r(2) = 0.83, p < 0.0001), followed by Australia
      (r(2) = 0.78, p < 0.0001), Canada (r(2) = 0.78, p < 0.0001) and the USA (r(2) =
      0.69, p < 0.0001). Japanese women showed no change in the number of finishers
      (r(2) = 0.01, p > 0.05). For men, athletes from France showed the steepest
      increase (r(2) = 0.85, p < 0.0001), followed by Austria (r(2) = 0.68, p <
      0.0001), Australia (r(2) = 0.67, p < 0.0001), Brazil (r(2) = 0.60, p < 0.0001),
      Great Britain (r(2) = 0.46, p < 0.0001), Germany (r(2) = 0.26, p < 0.0001), the
      United States of America (r(2) = 0.21, p = 0.013) and Switzerland (r(2) = 0.14, p
      = 0.0044). The number of Japanese men decreased (r(2) = 0.35, p = 0.0009). The
      number of men from Canada (r(2) = 0.02, p > 0.05) and New Zealand (r(2) = 0.02, p
      > 0.05) remained unchanged. Regarding female performance, the largest
      improvements were achieved by Japanese women (17.3%). The fastest race times in
      2012 were achieved by US-American women. Women from Japan, Canada, Germany,
      Australia, and the United States of America improved race times. For men, the
      largest improvements were achieved by athletes originating from Brazil (20.9%)
      whereas the fastest race times in 2012 were achieved by athletes from Germany.
      Race times for athletes originating from Brazil, Austria, Great Britain,
      Switzerland, Germany, Australia, Canada, Japan, New Zealand and France decreased.
      Race times in athletes originating from Australia and the United States of
      America showed no significant changes. Regarding the fastest race times ever, the
      fastest women originated from the United States (546 +/- 7 min) followed by Great
      Britain (555 +/- 15 min) and Switzerland (558 +/- 8 min). In men, the fastest
      finishers originated from the United States (494 +/- 7 min), Germany (496 +/- 6
      min) and Australia (497 +/- 5 min). CONCLUSIONS: The 'Ironman Hawaii' has been
      dominated by women and men from the United States of America in participation and
      performance.

PMID- 24735525
TI  - Development of the first-mention bias.
AB  - In many contexts, pronouns are interpreted as referring to the character
      mentioned first in the previous sentence, an effect called the 'first-mention
      bias'. While adults can rapidly use the first-mention bias to guide pronoun
      interpretation, it is unclear when this bias emerges during development.
      Curiously, experiments with children between two and three years old show
      successful use of order of mention, while experiments with older children (four
      to five years old) do not. While this could suggest U-shaped development, it
      could also reflect differences in the methodologies employed. We show that
      children can indeed use first-mention information, but do so too slowly to have
      been detected in previous work reporting null results. Comparison across the
      present and previously published studies suggests that the speed at which
      children deploy first-mention information increases greatly during the preschool
      years.

PMID- 24735526
TI  - Self-supported Li4Ti5O12-C nanotube arrays as high-rate and long-life anode
      materials for flexible Li-ion batteries.
AB  - Self-supported Li4Ti5O12-C nanotube arrays with high conductivity architectures
      are designed and fabricated for application in Li-ion batteries. The Li4Ti5O12
      nanotube arrays grow directly on stainless steel foil by a facile template-based
      solution route, further enhancing electronic conductivity by uniform carbon
      coating on the inner and outer surfaces of Li4Ti5O12 nanotubes. Owing to the
      shortened Li(+) diffusion distance, high contact surface area, sufficient
      conductivity, and very good structure stability of the nanotube arrays, the self
      supported Li4Ti5O12-C nanotube arrays exhibit remarkable rate capability (a
      reversible capability of 135 mA h g(-1), 105 mA h g(-1), and 80 mA h g(-1) at
      30C, 60C, and 100C, respectively) and cycling performance (approximate 7%
      capacity loss after 500 cycles at 10C with a capacity retention of 144 mA h g(
      1)). 

PMID- 24735527
TI  - Diterpenoids from Croton laui and their cytotoxic and antimicrobial activities.
AB  - Fourteen new diterpenoids including clerodane (1-12), labdane (13), and
      norlabdane (14) types, as well as nine known analogues were isolated from the
      aerial parts of Croton laui. Their structures were established on the basis of
      spectroscopic analysis, and that of crotonolide H (11) was confirmed by single
      crystal X-ray crystallography. Crotonolide A (1) exhibited moderate cytotoxicity
      against two tumor cell lines, HL-60 (human premyelocytic leukemia, IC50 9.42 MUM)
      and P-388 (murine leukemia, IC50 7.45 MUM), and crotonolide G (10) displayed
      significant antibacterial activity against a panel of Gram-positive bacteria. 

PMID- 24735528
TI  - Electronic and magnetic structure of LaSr-2*4 manganese oxide molecular sieve
      nanowires.
AB  - In this study we combine scanning transmission electron microscopy, electron
      energy loss spectroscopy and electron magnetic circular dichroism to get new
      insights into the electronic and magnetic structure of LaSr-2*4 manganese oxide
      molecular sieve nanowires integrated on a silicon substrate. These nanowires
      exhibit ferromagnetism with strongly enhanced Curie temperature (T c >500 K), and
      we show that the new crystallographic structure of these LaSr-2*4 nanowires
      involves spin orbital coupling and a mixed-valence Mn3+/Mn4+, which is a must for
      ferromagnetic ordering to appear, in line with the standard double exchange
      explanation. 

PMID- 24735529
TI  - Association of genetic variation of sodium taurocholate cotransporting
      polypeptide with chronic hepatitis B virus infection.
AB  - BACKGROUND: Sodium taurocholate cotransporting polypeptide (NTCP) plays an
      important role in the enterohepatic circulation of bile acids and hepatocyte
      function and was recently proposed to be a functional receptor for hepatitis B
      virus (HBV). OBJECTIVE: This study investigated the association of the functional
      polymorphism c.800C>T (p.S267F) (rs2296651) of the NTCP gene with HBV infection.
      METHODS: The study included 244 patients with chronic HBV infection, 76 HBV
      infection resolvers, and 113 healthy controls. The polymorphism was genotyped
      using the polymerase chain reaction-restriction fragment length polymorphism
      method. RESULTS: The distribution of the genotype and allele frequency of
      rs2296651 polymorphism was significantly different among the HBV patients, HBV
      infection resolvers, and healthy controls (p=0.034 and p=0.039, respectively).
      The frequency of genotype CT in HBV patients was significantly higher than that
      in healthy controls (11.9% vs. 4.4%, p=0.026, odds ratios [OR]=2.913, 95%
      confidence intervals [95% CI]=1.097-7.738). The frequency of allele T in HBV
      patients was also significantly higher than that in healthy controls (5.9% vs.
      2.2%, p=0.029, OR=2.793, 95% CI=1.067-7.312). The frequency of genotype CT and
      allele T in HBV patients was higher than that in HBV infection resolvers although
      the difference was not significant. The genotype and allele frequency between
      infection resolvers and healthy controls and between HBV patients with different
      clinical diseases had no significant difference. CONCLUSION: These findings
      suggest that the rs2296651 polymorphism may predispose the susceptibility to and
      chronicity of HBV infection.

PMID- 24735530
TI  - Simultaneous quantification of seven hippocampal neurotransmitters in depression
      mice by LC-MS/MS.
AB  - BACKGROUND: There is no method available to simultaneously detect GABA, Glu, Epi,
      NE, DA, 5-HT and 5-HIAA in mouse hippocampus. NEW METHOD: A rapid and sensitive
      LC-MS/MS method has been developed for simultaneously measuring seven
      neurotransmitters in mouse hippocampus. The analytes were detected in positive
      mode with multiple reaction monitoring (MRM) and the procedure was completed in
      less than 9min. RESULTS: This method exhibited excellent linearity for all of the
      analytes with regression coefficients higher than 0.99, and showed good intra-
      and inter-day precisions (RSD<15%) with good accuracy (80-120%). Moreover, the
      method was successfully applied for the quantitative determination of
      neurotransmitters in a mouse depression model induced by successive
      methylprednisolone injections. The results indicated that this depression model
      was closely associated with the decreased level of Epi (p=0.002) and elevated
      ratio of 5-HIAA/5-HT (p=0.01), which has never been reported elsewhere.
      COMPARISON WITH EXISTING METHOD(S): Compared with previous methods, current
      approach is more convenient without any pre-column derivatization of the analytes
      but enhances detectability with incremental neurotransmitter profile and shortens
      detection time. CONCLUSIONS: This work represents the first accurate simultaneous
      determination of seven neurotransmitters in the mouse depression model induced by
      methylprednisolone. The reliable method will benefit the research of neurological
      diseases with the altered neurotransmitter profile in brain.

PMID- 24735531
TI  - A novel technique for morphometric quantification of subarachnoid hemorrhage
      induced microglia activation.
AB  - BACKGROUND: Subarachnoid hemorrhage (SAH) is a neurologic catastrophe and poor
      outcome is typically attributed to vasospasm; however, there is also evidence
      that SAH causes a pro-inflammatory state and these two phenomena may be
      interrelated. SAH causes activation of microglia, but the time course and degree
      of microglial activation after SAH and its link to poor patient outcome and
      vasospasm remains unknown. NEW METHOD: Transgenic mice expressing eGFP under the
      control of the CX3CR1 locus, in which microglia are endogenously fluorescent,
      were randomly assigned to control or SAH groups. Immunohistochemistry for CD-68
      and CD-31 was performed at different time points after SAH. Using confocal
      microscopy and MatLab software, we have developed a novel technique to detect and
      quantify the stages of microglial activation and return to quiescence using an
      automated computerized morphometric analysis. RESULTS: We detected a
      statistically significant decrease in microglial process complexity 2 and 7 days
      following SAH. In addition, we detected a statistically significant increase in
      microglial domain volume 1 day following SAH; however, microglial domain volume
      returned to baseline by 2 days. COMPARISON WITH EXISTING METHOD: Most techniques
      for microglia assessment are qualitative, not quantitative, and are therefore
      inadequate to address the effects of anti-inflammatory drug treatment or other
      therapies after SAH. CONCLUSIONS: Using novel image analysis techniques we were
      able to reproducibly quantify activation of microglia following SAH, which will
      improve our ability to study the biology of microglial activation, and may
      ultimately improve management of disease progression and response to therapies
      directed at microglial activation.

PMID- 24735532
TI  - A novel recombinant baculovirus overexpressing a Bacillus thuringiensis Cry1Ab
      toxin enhances insecticidal activity.
AB  - Baculoviruses have been genetically modified to express foreign genes under
      powerful promoters in order to accelerate their speed of killing. In this study a
      truncated form of cry1Ab gene derived from Bacillus thuringinsis (Bt) subsp.
      aegypti isolate Bt7 was engineered into the genome of the baculovirus Autographa
      californica multiple nuclearpolyhedrosis wild type virus, in place of the
      polyhedrin gene by using homologous recombination in Spodoptera frugiperda (Sf)
      cells between a transfer vector carrying the Bt gene and the wild type virus
      linearized DNA. Recombinant wild type virus containing the cry1Ab gene was
      detected as blue occlusion-negative plaques in monolayers of Sf cells grown in
      the presence of X-Gal. In Sf cells infected with plaque-purified recombinant
      virus, the cry1Ab gene was expressed to yield a protein of approximately 82-kDa,
      as determined by immunoblot analysis. The toxicity of the recombinant virus
      expressing the insecticidal crystal protein (ICP) was compared to that of the
      wild-type virus. Infected-cell extract was toxic to cotton leaf worm Spodoptera
      littoralis second instar larvae and the estimated LC50 was 1.7 MUg/ml for the
      recombinant virus compared with that of wild-type virus which was 10 MUg/ml. 

PMID- 24735533
TI  - Taurine attenuates amyloid beta 1-42-induced mitochondrial dysfunction by
      activating of SIRT1 in SK-N-SH cells.
AB  - Amyloid beta (Abeta) plays a critical role in the pathogenesis of Alzheimer
      disease (AD). Studies indicate that Abeta causes reactive oxygen species (ROS)
      generation, mitochondrial dysfunction and neurons loss in vivo and in vitro.
      Taurine, a naturally occurring beta-amino acid in the brain, has been
      demonstrated to have neuroprotective properties. In the present study, the
      effects of taurine on cell viability and mitochondrial function in Abeta1-42
      treated SK-N-SH cells were investigated. Pretreatment of taurine significantly
      attenuated Abeta1-42-induced neuronal death. Similarly, taurine suppressed the
      mPTP opening and reversed mitochondrial function in the presence of Abeta1-42.
      Additionally, taurine attenuated the intracellular Ca(2+) and ROS generation
      induced by Abeta1-42. Moreover, the expression of Sirtuin 1 (SIRT1) was obviously
      recovered by taurine in Abeta1-42-treated SK-N-SH cells. Our results suggest that
      taurine prevents Abeta1-42-induced mitochondrial dysfunction by activation of
      SIRT1. This study implies that taurine is a prospective additive for AD patients.

PMID- 24735534
TI  - Curcumin-induced melanoma cell death is associated with mitochondrial
      permeability transition pore (mPTP) opening.
AB  - Here we studied the role of mitochondrial permeability transition pore (mPTP)
      opening in curcumin's cytotoxicity in melanoma cells. In cultured WM-115 melanoma
      cells, curcumin induced mitochondrial membrane potential (MPP) decrease,
      cyclophilin-D (CyPD)-adenine nucleotide translocator 1 (ANT-1) (two mPTP
      components) mitochondrial association and cytochrome C release, indicating mPTP
      opening. The mPTP blocker sanglifehrin A (SfA) and ANT-1 siRNA-depletion
      dramatically inhibited curcumin-induced cytochrome C release and WM-115 cell
      death. CyPD is required for curcumin-induced melanoma cell death. The CyPD
      inhibitor cyclosporin A (CsA) or CyPD siRNA-depletion inhibited curcumin-induced
      WM-115 cell death and apoptosis, while WM-115 cells with CyPD over-expression
      were hyper-sensitive to curcumin. Finally, we found that C6 ceramide enhanced
      curcumin-induced cytotoxicity probably through facilitating mPTP opening, while
      CsA and SfA as well as CyPD and ANT-1 siRNAs alleviated C6 ceramide's effect on
      curcumin in WM-115 cells. Together, these results suggest that curcumin-induced
      melanoma cell death is associated with mPTP opening.

PMID- 24735535
TI  - Thiamine deficiency results in release of soluble factors that disrupt
      mitochondrial membrane potential and downregulate the glutamate transporter
      splice-variant GLT-1b in cultured astrocytes.
AB  - Loss of astrocytic glutamate transporters is a major feature of both thiamine
      deficiency (TD) and Wernicke's encephalopathy. However, the underlying basis of
      this process is not well understood. In the present study we have investigated
      the possibility of release of astrocytic soluble factors that might be involved
      in the regulation of the glutamate transporter GLT-1b in these cells. Treatment
      of naive astrocytes with conditioned media from astrocytes exposed to TD
      conditions resulted in a progressive decrease in glutamate uptake over 24 h.
      Immunoblotting and flow cytometry measurements indicated this was accompanied by
      a 20-40% loss of GLT-1b. Astrocytes exposed to either TD or TD conditioned media
      showed increased disruption of mitochondrial membrane potential compared to
      control cells, and treatment of astrocytes with TD resulted in an increase in the
      pro-inflammatory cytokine TNF-alpha and elevated levels of phospho-IkappaB
      fragment, indicative of increased activation of NF-kappaB. Inhibition of TNF
      alpha activity with the use of a neutralizing antibody blocked the increased NF
      kappaB activation, while inhibition of NF-kappaB ameliorated the decrease in GLT
      1b and reversed the decrease in glutamate uptake occurring with TD treatment.
      Together, these findings indicate that astrocytes exposed to TD conditions show
      responses suggesting that soluble factors released by these cells under
      conditions of TD play a regulatory role in terms of glutamate transport function
      and mitochondrial integrity.

PMID- 24735536
TI  - Combined therapeutic potential of nuclear receptors with receptor tyrosine kinase
      inhibitors in lung cancer.
AB  - Cancer heterogeneity is a big hurdle in achieving complete cancer treatment,
      which has led to the emergence of combinational therapy. In this study, we
      investigated the potential use of nuclear receptor (NR) ligands for combinational
      therapy with other anti-cancer drugs. We first profiled all 48 NRs and 48
      biological anti-cancer targets in four pairs of lung cell lines, where each pair
      was obtained from the same patient. Two sets of cell lines were normal and the
      corresponding tumor cell lines while the other two sets consisted of primary
      versus metastatic tumor cell lines. Analysis of the expression profile revealed
      11 NRs and 15 cancer targets from the two pairs of normal versus tumor cell
      lines, and 9 NRs and 9 cancer targets from the primary versus metastatic tumor
      cell lines had distinct expression patterns in each category. Finally, the
      evaluation of nuclear receptor ligand T0901317 for liver X receptor (LXR)
      demonstrated its combined therapeutic potential with tyrosine kinase inhibitors.
      The combined treatment of cMET inhibitor PHA665752 or EGFR inhibitor gefitinib
      with T0901317 showed additive growth inhibition in both H2073 and H1993 cells.
      Mechanistically, the combined treatment suppressed cell cycle progression by
      inhibiting cyclinD1 and cyclinB expression. Taken together, this study provides
      insight into the potential use of NR ligands in combined therapeutics with other
      biological anti-cancer drugs.

PMID- 24735537
TI  - Differential AMPK phosphorylation by glucagon and metformin regulates insulin
      signaling in human hepatic cells.
AB  - Insulin and glucagon signaling in the liver are major contributors to glucose
      homeostasis. Patients with Type 1 and Type 2 diabetes have impaired glycemic
      control due, in part, to dysregulation of the opposing actions of these hormones.
      While hyperglucagonemia is a common feature in diabetes, its precise role in
      insulin resistance is not well understood. Recently, metformin, an AMPK
      activator, was shown to regulate hepatic glucose output via inhibition of
      glucagon-induced cAMP/PKA signaling; however, the mechanism for how PKA
      inhibition leads to AMPK activation in human hepatic cells is not known. Here we
      show that glucagon impairs insulin-mediated AKT phosphorylation in human hepatic
      cell line Huh7. This impairment of AKT activation by glucagon is due to PKA
      mediated inhibition of AMPK via increased inhibitory phosphorylation of
      AMPK(Ser173) and reduced activating phosphorylation of AMPK(Thr172). In contrast,
      metformin decreases PKA activity, leading to decreased pAMPK(Ser173) and
      increased pAMPK(Thr172). These data support a novel mechanism involving PKA
      dependent AMPK phosphorylation that provides new insight into how glucagon and
      metformin modulate hepatic insulin resistance. 

PMID- 24735538
TI  - Novel nitric oxide generating compound glycidyl nitrate enhances the therapeutic
      efficacy of chemotherapy and radiotherapy.
AB  - Selective release of nitric oxide (NO) in tumors could improve the tumor blood
      flow and drug delivery for chemotherapeutic agents and radiotherapy, thereby
      increasing the therapeutic index. Glycidyl nitrate (GLYN) is a NO generating
      small molecule, and has ability to release NO on bioactivation in SCC VII tumor
      cells. GLYN-induced intracellular NO generation was significantly attenuated by
      NO scavenger carboxy-PTIO (cPTIO) and NAC. GLYN significantly increases tumor
      blood flow, but has no effect on the blood flow of normal tissues in tumor
      bearing mice. When used with cisplatin, GLYN significantly increased the tumor
      growth inhibition effect of cisplatin. GLYN also had a modest radiosensitizing
      effect in vitro and in vivo. GLYN was well tolerated and there were no acute
      toxicities found at its effective therapeutic doses in preclinical studies. These
      results suggest that GLYN is a promising new drug for use with chemotherapy and
      radiotherapy, and provide a compelling rationale for future studies of GLYN and
      related compounds.

PMID- 24735539
TI  - A mutation in the heparin-binding site of noggin as a novel mechanism of proximal
      symphalangism and conductive hearing loss.
AB  - The access of bone morphogenetic protein (BMP) to the BMP receptors on the cell
      surface is regulated by its antagonist noggin, which binds to heparan-sulfate
      proteoglycans on the cell surface. Noggin is encoded by NOG and mutations in the
      gene are associated with aberrant skeletal formation, such as in the autosomal
      dominant disorders proximal symphalangism (SYM1), multiple synostoses syndrome,
      Teunissen-Cremers syndrome, and tarsal-carpal coalition syndrome. NOG mutations
      affecting a specific function may produce a distinct phenotype. In this study, we
      investigated a Japanese pedigree with SYM1 and conductive hearing loss and found
      that it carried a novel heterozygous missense mutation of NOG (c.406C>T; p.R136C)
      affecting the heparin-binding site of noggin. As no mutations of the heparin
      binding site of noggin have previously been reported, we investigated the crystal
      structure of wild-type noggin to investigate molecular mechanism of the p.R136C
      mutation. We found that the positively charged arginine at position 136 was
      predicted to be important for binding to the negatively charged heparan-sulfate
      proteoglycan (HSPG). An in silico docking analysis showed that one of the salt
      bridges between noggin and heparin disappeared following the replacement of the
      arginine with a non-charged cysteine. We propose that the decreased binding
      affinity of NOG with the p.R136C mutation to HSPG leads to an excess of BMP
      signaling and underlies the SYM1 and conductive hearing loss phenotype of
      carriers.

PMID- 24735541
TI  - Possible involvement of insulin-like growth factor 2 mRNA-binding protein 3 in
      zebrafish oocyte maturation as a novel cyclin B1 mRNA-binding protein that
      represses the translation in immature oocytes.
AB  - In immature zebrafish oocytes, dormant cyclin B1 mRNAs localize to the animal
      polar cytoplasm as aggregates. After hormonal stimulation, cyclin B1 mRNAs are
      dispersed and translationally activated, which are necessary and sufficient for
      the induction of zebrafish oocyte maturation. Besides cytoplasmic polyadenylation
      element-binding protein (CPEB) and cis-acting elements in the 3' untranslated
      region (UTR), Pumilio1 and a cis-acting element in the coding region of cyclin B1
      mRNA are important for the subcellular localization and timing of translational
      activation of the mRNA. However, mechanisms underlying the spatio-temporal
      control of cyclin B1 mRNA translation during oocyte maturation are not fully
      understood. We report that insulin-like growth factor 2 mRNA-binding protein 3
      (IMP3), which was initially described as a protein bound to Vg1 mRNA localized to
      the vegetal pole of Xenopus oocytes, binds to the 3' UTR of cyclin B1 mRNA that
      localizes to the animal pole of zebrafish oocytes. IMP3 and cyclin B1 mRNA co
      localize to the animal polar cytoplasm of immature oocytes, but in mature
      oocytes, IMP3 dissociates from the mRNA despite the fact that its protein content
      and phosphorylation state are unchanged during oocyte maturation. IMP3 interacts
      with Pumilio1 and CPEB in an mRNA-dependent manner in immature oocytes but not in
      mature oocytes. Overexpression of IMP3 and injection of anti-IMP3 antibody
      delayed the progression of oocyte maturation. On the basis of these results, we
      propose that IMP3 represses the translation of cyclin B1 mRNA in immature
      zebrafish oocytes and that its release from the mRNA triggers the translational
      activation.

PMID- 24735540
TI  - A novel cantharidin analog N-benzylcantharidinamide reduces the expression of MMP
      9 and invasive potentials of Hep3B via inhibiting cytosolic translocation of HuR.
AB  - Invasion and metastasis are major causes of malignant tumor-associated mortality.
      The present study aimed to investigate the molecular events underlying inhibitory
      effect of N-benzylcantharidinamide, a novel synthetic analog of cantharidin, on
      matrix metalloproteinase-9 (MMP-9)-mediated invasion in highly metastatic
      hepatocellular carcinoma Hep3B cells. In this investigation, among six analogs of
      cantharidin, only N-benzylcantharidinamide has the inhibitory action on MMP-9
      expression at non-toxic dose. The MMP-9 expression and invasion of Hep3B cells
      were significantly suppressed by treatment of N-benzylcantharidinamide in a dose
      dependent manner. On the other hand, the transcriptional activity of MMP-9
      promoter and nuclear levels of NF-kappaB and AP-1 as the main transcriptional
      factors inducing MMP-9 expression were not affected by it although the level of
      MMP-9 mRNA was reduced by treatment of N-benzylcantharidinamide. Interestingly,
      the stability of MMP-9 mRNA was significantly reduced by N-benzylcantharidinamide
      treatment. In addition, the cytosolic translocation of human antigen R (HuR),
      which results in the increase of MMP-9 mRNA stability through interaction of HuR
      with 3'-untranslated region of MMP-9 mRNA, was suppressed by treatment of N
      benzylcantharidinamide, in a dose-dependent manner. Taken together, it was
      demonstrated, for the first time, that N-benzylcantharidinamide suppresses MMP-9
      expression by reducing HuR-mediated MMP-9 mRNA stability for the inhibition of
      invasive potential in highly metastatic Hep3B cells.

PMID- 24735542
TI  - A de novo germline mutation of APC for inheritable colon cancer in a Chinese
      family using multigene next generation sequencing.
AB  - Inheritable colorectal cancers (CRC) accounted for about 20% of the CRC cases,
      such as hereditary nonpolyposis colorectal cancer (HNPCC), Gardner syndrome and
      familial adenomatous polyposis (FAP). A four-generation Han Chinese family was
      found affected with polyposis in colons. Inferred from the pedigree structure,
      the disease in this family showed an autosomal dominant inheritance model. To
      locate the causal mutations in this family, genomic DNAs were extracted and the
      next generation sequencing for 5 genes relating to colon cancer performed by Ion
      Torrent Personal Genome Machine with a 314 chip. The reads were aligned with
      human reference genome hg19 to call variants in the 5 genes. After analysis, 14
      variants were detected in the sequenced sample and 13 been collected in dbSNP
      database and assigned with a rs identification number. In these variants, 9 were
      synonymous, 4 missense and 1 non-sense. In them, 2 rare variants (c.694C>T in APC
      and c.1690A>G in MSH2) might be the putative causal mutations for familial
      adenomatous polyposis (FAP) since the rarity of the mutated allele in normal
      controls. c.694C>T was detected in only affected members and generated a
      premature stop codon in APC. It should be a de novo germline mutation making APC
      containing this stop codon as targets for nonsense-mediated mRNA decay (NMD).
      c.1690A>G in MSH2 was not only detected in affected members, but also in normal
      ones in the family. Functional prediction revealed that the amino acid affected
      by this variant had no effect on the function of MSH2. Here, we report a de novo
      germline mutation of APC as the causal variant in a Chinese family with
      inheritable colon cancer by the next generation sequencing.

PMID- 24735543
TI  - MicroRNA-181b promotes ovarian cancer cell growth and invasion by targeting
      LATS2.
AB  - MicroRNAs (miRNAs) are strongly implicated in tumorigenesis and metastasis. In
      this study, we showed significant upregulation of miR-181b in ovarian cancer
      tissues, compared with the normal ovarian counterparts. Forced expression of miR
      181b led to remarkably enhanced proliferation and invasion of ovarian cancer
      cells while its knockdown induced significant suppression of these cellular
      events. The tumor suppressor gene, LATS2 (large tumor suppressor 2), was further
      identified as a novel direct target of miR-181b. Specifically, miR-181b bound
      directly to the 3'-untranslated region (UTR) of LATS2 and suppressed its
      expression. Restoration of LATS2 expression partially reversed the oncogenic
      effects of miR-181b. Our results indicate that miR-181b promotes proliferation
      and invasion by targeting LATS2 in ovarian cancer cells. These findings support
      the utility of miR-181b as a potential diagnostic and therapeutic target for
      ovarian cancer.

PMID- 24735544
TI  - Differential interferon pathway gene expression patterns in Rhabdomyosarcoma
      cells during Enterovirus 71 or Coxsackievirus A16 infection.
AB  - Exposure of cells to type I interferon (IFN) induces an antiviral state that
      prevents viral infection, but viruses can utilize multiple tactics to antagonize
      the host immune system. Enterovirus 71 (EV71) and Coxsackievirus A16 (CVA16) are
      two major pathogens that cause hand, foot, and mouth disease (HFMD), which is
      prevalent among children. We found that both EV71 and CA16 have different
      reactions to type I IFN pretreatment and induction patterns of type I IFN on
      Rhabdomyosarcoma (RD) cells. Further, a human-alpha and beta IFN PCR array was
      employed to analyze the expressions of 84 genes related to the type I IFN
      pathway. We found significant up-regulation of multiple genes in the presence of
      type I IFN and differential regulation patterns during EV71 or CA16 infection in
      RD cells. For instance, EV71 infection repressed the JAK-STAT signaling pathway
      and interferon-stimulated gene (ISG) expression, whereas CA16 infection normally
      triggers the JAK-STAT pathway, leading to the expression of ISGs. Taken together,
      this study provides a comprehensive view of the differential impacts of EV71 and
      CA16 infection on 84 genes in the IFN pathway, shedding light on the different
      resistances of these viruses to type I IFN treatment and cytotoxic effects in RD
      cells.

PMID- 24735545
TI  - Polyomavirus BK-encoded microRNA suppresses autoregulation of viral replication.
AB  - Polyomavirus BK (BKV) infection is an important cause of renal allograft failure.
      Viral microRNAs are known to play a crucial role in viral replication. This study
      investigated the expression of BKV-encoded microRNAs (miR-B1) in patients with
      polyomavirus-associated nephropathy (PVAN) and their role in viral replication.
      Following BKV infection in renal proximal tubular cells, the 3p and 5p miR-B1
      levels were significantly increased. Cells transfected with the vector containing
      the miR-B1 precursor (the miR-B1 vector) showed a significant increase in
      expression of 3p and 5p miR-B1 and decrease in luciferase activity of a reporter
      containing the 3p and 5p miR-B1 binding sites, compared to cells transfected with
      the miR-B1-mutated vector. Transfection of the miR-B1 expression vector or the 3p
      and 5p miR-B1 oligonucleotides inhibited expression of TAg. TAg-enhanced promoter
      activity and BKV replication were inhibited by miR-B1. In contrast, inhibition of
      miR-B1 expression by addition of miR-B1 antagomirs or silencing of Dicer
      upregulated the expression of TAg and VP1 proteins in BKV-infected cells.
      Importantly, patients with PVAN had significantly higher levels of 3p and 5p miR
      B1 compared to renal transplant patients without PVAN. In conclusion, we
      demonstrated that (1) miR-B1 expression was upregulated during BKV infection and
      (2) miR-B1 suppressed TAg-mediated autoregulation of BKV replication. Use of miR
      B1 can be evaluated as a potential treatment strategy against BKV infection.

PMID- 24735546
TI  - Incidence and survival trends of head and neck squamous cell carcinoma in the
      Netherlands between 1989 and 2011.
AB  - BACKGROUND: Incidence and survival trends of head and neck squamous cell
      carcinoma (HNSCC) are essential knowledge for guiding policy making and research.
      METHODS: The total population of the Netherlands was studied covering 1989-2011.
      Two-and five-year survival and age-standardized incidence rates of HNSCC were
      assessed in relation to site, gender and age (15 years-of-age categories).
      RESULTS: We recorded a statistically significant increase of oral, oropharyngeal
      and hypopharyngeal carcinoma for males and females of all ages, varying from 0.6%
      (hypopharynx in males) to 2.7% (oropharynx in females) per year. The incidence of
      laryngeal carcinoma significantly decreased for males with 2.3% per year; for
      females the situation was stable. In young adults (below 45 years of age) the
      incidence figures were different: significant decreasing incidence trends were
      seen for both genders for carcinomas of the oropharynx, hypopharynx and larynx.
      Regarding oral carcinoma, no change was observed for the young patient group, but
      for subsites trends were divergent. Carcinoma of the floor or mouth decreased for
      both genders, but carcinoma of the tongue rose by a significant 2.8% per year for
      young males. Five-year survival trends for all ages showed no change for
      laryngeal carcinoma, a small improvement for oral and hypopharyngeal carcinoma,
      and a substantial and significant improvement of survival from 36% to 47%
      survival over the total period for oropharyngeal carcinoma. CONCLUSION: In the
      Netherlands for the last two decades, the incidence of oral, oropharyngeal and
      hypopharyngeal squamous cell carcinoma has increased and survival has improved.
      The incidence of laryngeal carcinoma has decreased in males, and remained
      unchanged in females; survival from laryngeal carcinoma has not changed.

PMID- 24735547
TI  - Linifanib (ABT-869), enhances cytotoxicity with poly (ADP-ribose) polymerase
      inhibitor, veliparib (ABT-888), in head and neck carcinoma cells.
AB  - OBJECTIVES: PARP inhibitors (PARPi) may provide an opportunity to gain selective
      killing of tumor cells which have deficiencies in cellular DNA repair systems. We
      previously demonstrated linifanib (ABT-869), a multi-receptor tyrosine kinase
      inhibitor of VEGF and PDGF receptor families, radiosensitized Head and Neck
      Squamous Cell Carcinoma cells (HNSCC) via inhibiting STAT3 activation. Given that
      STAT3 can modulate DNA damage response (DDR) pathway, in this study, we evaluate
      the effects of linifanib to enhance cytotoxicity with the PARPi, veliparib (ABT
      888), in HNSCC. MATERIALS AND METHODS: UMSCC-22A and UMSCC-22B cells were treated
      with linifanib (ABT-869) and veliparib (ABT-888). Cell viability, cytotoxicity,
      apoptosis induction, DNA single strand break (SSB) and double strand break (DSB)
      damages were examined by MTT assay, colony formation assay, flow cytometry and
      comet assay. In addition, the expression of DNA homologous recombination repair
      protein Rad51, gammaH2AX, a double strand break marker and cleaved PARP, an
      apoptotic cell death marker, were assessed using western immunoblotting. RESULTS:
      Combination treatment resulted in more cell growth inhibition, induction of
      apoptosis, DNA damages and double strand breaks, lower expression of Rad51,
      increase gammaH2AX expression and PARP cleavage. CONCLUSION: These data suggest
      the possibility of combining targeted therapeutic such as linifanib with
      veliparib to augment the inhibition of cell growth and apoptosis via synthetic
      lethality in HNSCC cells. Thus, it may provide a novel therapeutic strategy and
      improve efficacy and outcome in HNSCC.

PMID- 24735548
TI  - Unintentional drowning deaths in the United States, 1999-2010.
AB  - This report provides recent findings on unintentional drowning deaths in the
      United States. Children under 5 years of age and adults aged 85 and over had the
      highest risk of drowning, although the rates for these age groups reached their
      lowest point in 2010. Drowning death rates decreased over time for all age groups
      except for adults aged 45-84. Drowning remained the second leading cause of death
      from unintentional injury for girls aged 1-4 years. For boys aged 1-4 years,
      unintentional drowning has been the leading cause of death from unintentional
      injury since 2005. Patterns of drowning by place differed by sex and age. More
      than one-half of all drowning deaths for males occurred in natural water compared
      with only one-quarter of all drowning deaths for females. Drowning was most
      likely to occur in the bath tub for infants under the age of 1 year and for
      adults aged 85 and over, in swimming pools for children aged 1-4 years, and in
      natural water for persons aged 5-84 years. These findings are consistent with the
      results from previous studies. Although the percentage of drowning occurring in
      some locations changed slightly over time, the pattern of drowning in particular
      locations by sex and age remained the same.

PMID- 24735549
TI  - Context matters in heart failure self-care: a qualitative systematic review.
AB  - BACKGROUND: The aim of this work was to identify the main contextual factors and
      processes that influence patients' self-care of heart failure (HF). METHODS AND
      RESULTS: A systematic review was conducted with the use of qualitative meta
      synthesis. Ten databases were searched up to March 19, 2012. Of the 1,421 papers
      identified by the systematic search, 45 studies were included in this meta
      synthesis. To be included, studies had to contain a qualitative research
      component, data pertaining to self-care of HF from adults (>=18 y) and be
      published as full papers or theses since 1995. These studies involved: 1,398
      patients (mean age 65.9 y), 180 caregivers, and 63 health professionals. Six main
      types of contextual factors were found to influence HF self-care in the studies:
      caregivers; social networks and social support; place; finances and financial
      capacity; work and occupation; and HF support groups and programs. CONCLUSION: HF
      self-care is influenced by contextual elements that fall outside of traditional
      elements of a HF self-care program. Inclusion of these elements may help to
      address the current concerns about poor adherence to self-management programs.

PMID- 24735550
TI  - Adapting a community-based ART delivery model to the patients' needs: a mixed
      methods research in Tete, Mozambique.
AB  - BACKGROUND: To improve retention in antiretroviral therapy (ART), lessons learned
      from chronic disease care were applied to HIV care, providing more
      responsibilities to patients in the care of their chronic disease. In Tete-
      Mozambique, patients stable on ART participate in the ART provision and peer
      support through Community ART Groups (CAG). This article analyses the evolution
      of the CAG-model during its implementation process. METHODS: A mixed method
      approach was used, triangulating qualitative and quantitative findings. The
      qualitative data were collected through semi-structured focus groups discussions
      and in-depth interviews. An inductive qualitative content analysis was applied to
      condense and categorise the data in broader themes. Health outcomes, patients'
      and groups' characteristics were calculated using routine collected data. We
      applied an 'input--process--output' pathway to compare the initial planned
      activities with the current findings. RESULTS: Input wise, the counsellors were
      considered key to form and monitor the groups. In the process, the main
      modifications found were the progressive adaptations of the daily CAG functioning
      and the eligibility criteria according to the patients' needs. Beside the
      anticipated outputs, i.e. cost and time saving benefits and improved treatment
      outcomes, the model offered a mutual adherence support and protective environment
      to the members. The active patient involvement in several health activities in
      the clinics and the community resulted in a better HIV awareness, decreased
      stigma, improved health seeking behaviour and better quality of care.
      CONCLUSIONS: Over the past four years, the modifications in the CAG-model
      contributed to a patient empowerment and better treatment outcomes. One of the
      main outstanding questions is how this model will evolve in the future. Close
      monitoring is essential to ensure quality of care and to maintain the core
      objective of the CAG-model 'facilitating access to ART care' in a cost and time
      saving manner.

PMID- 24735551
TI  - A prenatal missed diagnosed case of submicroscopic chromosomal abnormalities by
      karyotyping: the clinical utility of array-based CGH in prenatal diagnostics.
AB  - BACKGROUND: Array-based comparative genomic hybridization possesses a number of
      significant advantages over conventional cytogenetic and other molecular
      cytogenetic techniques, providing a sensitive and comprehensive detection
      platform for unexpected imbalances in the genome wide. CASE PRESENTATION: The
      newborn proband, demonstrated with craniofacial dysmorphism and multiple
      malformations, was born to a family with spontaneous abortions. This pregnancy
      was uneventful, except the prenatal ultrasound examination showed an increased
      nuchal translucency at 12(+) weeks of gestation. Cytogenetics revealed an
      apparently normal karyotype, and the couple decided to continue the pregnancy.
      Array-based CGH analysis was applied to the affected infant, identified a
      combination of 18p deletion and 7q duplication. Further study indicates that the
      unbalanced translocation was inherited from a balanced translocation carrier
      parent. CONCLUSIONS: In review of the case, several overlooked points leading to
      the missed diagnosis should be discussed and certain quality control strategies
      should be adopted to avoid similar problems in the future. Array-based CGH and
      karyotyping techniques are complemented by diverse detection spectrum and
      resolutions, and a combination of these methods could help providing optimal
      genetic diagnosis. Given that the array-CGH analysis will not introduce
      additional risk to patients, it is reasonable to recommend those already
      undergoing invasive testing should take array-based CGH as an adjunct to
      conventional cytogenetic tests and other molecular cytogenetic analysis.

PMID- 24735552
TI  - MicroRNAs involving in cold, wounding and salt stresses in Triticum aestivum L.
AB  - MicroRNAs (miRNAs) play critical roles in post-transcriptional regulation and act
      as important endogenous regulators to various stresses. Cold, wounding and high
      salinity are three common environmental stress stimuli influencing crops growth
      and development. In this study, we identified 31 known miRNAs and 3 novel miRNAs
      in wheat. Moreover, 19 stress-regulated miRNAs using RT-qPCR data in which the
      effects of three stresses were surveyed from the known miRNAs. Among them, 16, 12
      and 8 miRNAs were regulated under cold, wounding and high-salinity treatments,
      respectively. Of which 4 miRNAs were highly responsive to cold stress in wheat by
      northern blot, and 6 wounding-regulated and 3 high-salinity-regulated miRNAs were
      detected. Meanwhile, miR159, miR393 and miR398 were responsive to multiple stress
      stimuli. Besides, 2 novel miRNAs were regulated by cold stress. While, the
      analyses of targets suggested miR159, miR398 and miR6001 could responses to
      stress conditions in regulation pathways. Taken together, the results of this
      study suggest that wheat miRNAs may play important roles in response to abiotic
      stress.

PMID- 24735553
TI  - Isolation and characterization of Korean pine (Pinus koraiensis) convicilin.
AB  - A vicilin-like globulin seed storage protein, termed convicilin, was isolated for
      the first time from Korean pine (Pinus koraiensis). SDS-PAGE analysis revealed
      that Korean pine convicilin was post-translationally processed. The N-terminal
      peptide sequences of its components were determined. These peptides could be
      mapped to a protein translated from an embryo abundant transcript isolated in
      this study. Similar to vicilin, native convicilin appeared to be homotrimeric.
      Differential scanning calorimetry (DSC) analyses revealed that this protein is
      less resistant to thermal treatment than Korean pine vicilin. Its transition
      temperature was 75.57  degrees C compared with 84.13  degrees C for vicilin. The
      urea induced folding-unfolding equilibrium of pine convicilin monitored by
      intrinsic fluorescence could be interpreted in terms of a two-state model, with a
      Cm of 4.41 +/- 0.15 M.

PMID- 24735555
TI  - Application of response surface methodology for optimization of natural organic
      matter degradation by UV/H2O2 advanced oxidation process.
AB  - BACKGROUND: In this research, the removal of natural organic matter from aqueous
      solutions using advanced oxidation processes (UV/H2O2) was evaluated. Therefore,
      the response surface methodology and Box-Behnken design matrix were employed to
      design the experiments and to determine the optimal conditions. The effects of
      various parameters such as initial concentration of H2O2 (100-180 mg/L), pH (3
      11), time (10-30 min) and initial total organic carbon (TOC) concentration (4-10
      mg/L) were studied. RESULTS: Analysis of variance (ANOVA), revealed a good
      agreement between experimental data and proposed quadratic polynomial model (R(2)
      = 0.98). Experimental results showed that with increasing H2O2 concentration,
      time and decreasing in initial TOC concentration, TOC removal efficiency was
      increased. Neutral and nearly acidic pH values also improved the TOC removal.
      Accordingly, the TOC removal efficiency of 78.02% in terms of the independent
      variables including H2O2 concentration (100 mg/L), pH (6.12), time (22.42 min)
      and initial TOC concentration (4 mg/L) were optimized. Further confirmation tests
      under optimal conditions showed a 76.50% of TOC removal and confirmed that the
      model is accordance with the experiments. In addition TOC removal for natural
      water based on response surface methodology optimum condition was 62.15%.
      CONCLUSIONS: This study showed that response surface methodology based on Box
      Behnken method is a useful tool for optimizing the operating parameters for TOC
      removal using UV/H2O2 process.

PMID- 24735554
TI  - Rapid kinetics of endocytosis at rod photoreceptor synapses depends upon
      endocytic load and calcium.
AB  - Release from rods is triggered by the opening of L-type Ca2+ channels that lie
      beneath synaptic ribbons. After exocytosis, vesicles are retrieved by
      compensatory endocytosis. Previous work showed that endocytosis is dynamin
      dependent in rods but dynamin-independent in cones. We hypothesized that fast
      endocytosis in rods may also differ from cones in its dependence upon the amount
      of Ca2+ influx and/or endocytic load. We measured exocytosis and endocytosis from
      membrane capacitance (C m) changes evoked by depolarizing steps in voltage
      clamped rods from tiger salamander retinal slices. Similar to cones, the time
      constant for endocytosis in rods was quite fast, averaging <200 ms. We
      manipulated Ca2+ influx and the amount of vesicle release by altering the
      duration and voltage of depolarizing steps. Unlike cones, endocytosis kinetics in
      rods slowed after increasing Ca2+ channel activation with longer step durations
      or more strongly depolarized voltage steps. Endocytosis kinetics also slowed as
      Ca2+ buffering was decreased by replacing BAPTA (10 or 1 mM) with the slower Ca2+
      buffer EGTA (5 or 0.5 mM) in the pipette solution. These data provide further
      evidence that endocytosis mechanisms differ in rods and cones and suggest that
      endocytosis in rods is regulated by both endocytic load and local Ca2+ levels. 

PMID- 24735556
TI  - Abstracts of the IPA World Congress 2014, May 9-11, 2014, Athens, Greece.

PMID- 24735557
TI  - Raman microspectroscopy imaging study on topochemical correlation between lignin
      and hydroxycinnamic acids in Miscanthus sinensis.
AB  - Confocal Raman microspectroscopy (CRM) has emerged as a powerful approach to
      visualize the compositional distribution in lignocellulosic biomass of cell
      walls. In this work, the applicability of CRM for imaging the topochemical
      correlation between lignin and hydroxycinnamic acids (HCA) in the Miscanthus
      sinensis internode was explored. Model compound [p-coumaric acid (PCA) and
      ferulic acid (FA)] analysis indicated that the band region from 1,152 to 1,197
      cm(-1) can be used to characterize the distribution of HCA. Raman images
      calculated by integrating over the area intensity of characteristic spectral
      regions showed heterogeneous distribution of lignin and HCA at cellular and sub
      cellular level. When overlaying the Raman image of lignin and HCA distribution,
      it was found that these two polymers were co-located in the middle lamella and
      secondary wall of corresponding cells. Raman images for the band intensity ratio
      (1,173 cm(-1)/1,603 cm(-1)) indicated a clear association between lignin and HCA
      distribution within morphologically distinct cell wall layers of sclerenchyma
      fibers and the parenchyma. This is the first time that the spatial correlation
      between lignin and HCA concentration has been illustrated by a microspectroscopy
      imaging approach. The results are of importance in extending the current
      understanding of lignin and aromatics topochemistry in herbaceous biomass.

PMID- 24735558
TI  - CABS-flex predictions of protein flexibility compared with NMR ensembles.
AB  - MOTIVATION: Identification of flexible regions of protein structures is important
      for understanding of their biological functions. Recently, we have developed a
      fast approach for predicting protein structure fluctuations from a single protein
      model: the CABS-flex. CABS-flex was shown to be an efficient alternative to
      conventional all-atom molecular dynamics (MD). In this work, we evaluate CABS
      flex and MD predictions by comparison with protein structural variations within
      NMR ensembles. RESULTS: Based on a benchmark set of 140 proteins, we show that
      the relative fluctuations of protein residues obtained from CABS-flex are well
      correlated to those of NMR ensembles. On average, this correlation is stronger
      than that between MD and NMR ensembles. In conclusion, CABS-flex is useful and
      complementary to MD in predicting protein regions that undergo conformational
      changes as well as the extent of such changes. AVAILABILITY AND IMPLEMENTATION:
      The CABS-flex is freely available to all users at
      http://biocomp.chem.uw.edu.pl/CABSflex. CONTACT: sekmi@chem.uw.edu.pl
      SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics
      online.

PMID- 24735559
TI  - Basics and recent advances of two dimensional- polyacrylamide gel
      electrophoresis.
AB  - Gel- based proteomics is one of the most versatile methods for fractionating
      protein complexes. Among these methods, two dimensional- polyacrylamide gel
      electrophoresis (2-DE) represents a mainstay orthogonal approach, which is
      popularly used to simultaneously fractionate, identify, and quantify proteins
      when coupled with mass spectrometric identification or other immunological tests.
      Although 2-DE was first introduced more than three decades ago, several
      challenges and limitations to its utility still exist. This review discusses the
      principles of 2-DE as well as both recent methodological advances and new
      applications. 

PMID- 24735560
TI  - Health and human services director Sebelius resigns.

PMID- 24735561
TI  - Adherence to antiretroviral therapy and its associated factors among children at
      South Wollo Zone Hospitals, Northeast Ethiopia: a cross-sectional study.
AB  - BACKGROUND: Poor adherence to antiretroviral therapy negatively affects the
      suppression of viral replication. It increases risks of drug resistance,
      treatment failure, Acquired Immuno Deficiency Syndrome (AIDS)-related morbidity
      and mortality among children. This study assessed the level of adherence to
      antiretroviral therapy and its associated factors among children at hospitals in
      South Wollo Zone, Northeast Ethiopia. METHODS: An institution-based cross
      sectional study was conducted among Human Immunodeficiency Virus (HIV)-infected
      children in April 2013. A total of 464 children who were taking Antiretroviral
      Therapy (ART) in the hospitals were included. Data were collected using pretested
      and structured questionnaires using a face-to-face interview method. Descriptive
      and summary statistics were employed. Bivariate and multiple logistic regressions
      were computed. Odds ratios and their 95% confidence intervals were computed to
      determine the level of significance. RESULTS: Of the 464 study samples, 440
      children with their caregivers were included in the final analysis. A total of
      78.6% of the caregivers reported that their children were adherent to
      antiretroviral therapy in the month prior to the interview. Caregivers' knowledge
      about antiretroviral treatment [AOR = 2.72(95% CI: 1.82, 5.39)], no current
      substance use of the caregivers [Adjusted Odds Ratio (AOR) = 2.21(95% Confidence
      Interval (CI): 1.34, 7.13)], proximity to the health care facility [AOR =
      2.31(95% CI: 1.94, 4.63)], if the child knows HIV-positive status [AOR = 3.47(95%
      CI: 2.10, 6.81)] and caregiver's educational status [AOR = 0.59(95% CI: 0.21,
      0.82)] were significantly and independently associated with adherence of children
      to antiretroviral therapy. CONCLUSION: Adherence of antiretroviral therapy in
      this study was comparable to other studies conducted in developing countries.
      Caregiver's knowledge about antiretroviral therapy, no current use of substances,
      close proximity to health facilities, and letting child's know his/her HIV status
      improves adherence to antiretroviral therapy. Health care providers should
      educate caregivers about antiretroviral therapy and encourage HIV positive status
      disclosure to the child.

PMID- 24735562
TI  - Infant mortality statistics from the 2010 period linked birth/infant death data
      set.
AB  - OBJECTIVES: This report presents 2010 period infant mortality statistics from the
      linked birth/infant death data set (linked file) by maternal and infant
      characteristics. The linked file differs from the mortality rate declined
      mortality file, which is based entirely on death certificate data. METHODS:
      Descriptive tabulations of data are presented and interpreted. RESULTS: The U.S.
      infant mortality rate was 6.14 infant deaths per 1,000 live births in 2010, 4%
      lower than the rate of 6.39 in 2009. The number of infant deaths was 24,572 in
      2010, a decline of 1,836 infant deaths from 2009. From 2009 to 2010, the infant
      mortality rate declined 8% for non-Hispanic black mothers to 11.46, and 3% for
      non-Hispanic white mothers to 5.18. Asian or Pacific Islander mothers had the
      lowest rate in 2010 (4.27). From 2009 to 2010, the neonatal mortality rate
      declined by 3% to 4.05 neonatal deaths per 1,000 live births, while the
      postneonatal mortality rate declined 5% to 2.10. In 2010, infants born at 37-38
      weeks of gestation (early term) had infant mortality rates that were 62% higher
      than those born at 39-41 weeks of gestation. For multiple births, the infant
      mortality rate was 25.41, almost five times the rate of 5.45 for singleton
      births. The three leading causes of infant death-congenital malformations, low
      birthweight, and sudden infant death syndrome-accounted for 46% of all infant
      deaths. In 2010, 35.2% of infant deaths were preterm-related.

PMID- 24735563
TI  - Soluble human leukocyte antigen-G in seminal plasma is associated with HLA-G
      genotype: possible implications for fertility success.
AB  - PROBLEM: We have previously shown that human seminal plasma contains
      immunomodulatory soluble HLA-G (sHLA-G). We investigated whether sHLA-G levels in
      seminal plasma are associated with a specific 14 base pair (bp)
      insertion/deletion (ins/del) polymorphism in the 3'-untranslated region of the
      HLA-G gene and/or with the outcome of assisted reproduction treatments (ART) in
      couples attending a fertility clinic. METHOD OF STUDY: In a total of 54
      unselected couples, sHLA-G levels were measured in seminal plasma samples and
      blood samples, HLA-G genotyping was performed, and clinical data were collected.
      RESULTS: The concentration of sHLA-G in seminal plasma samples was significantly
      associated with the HLA-G 14 bp ins/del genotype of the men; the del14 bp/del14
      bp genotype showed the highest level of sHLA-G, and the ins14 bp/ins14 bp
      genotype showed the lowest level (P = 0.003). We observed a trend for higher
      seminal plasma levels of sHLA-G/total protein and total sHLA-G in cases with
      reduced semen quality, where the female partner became pregnant after ART,
      compared with those couples in which no pregnancy was achieved. CONCLUSION: These
      first results are in accordance with a possible role of seminal sHLA-G as an
      immunomodulatory factor in the female reproductive tract before and at the time
      of conception.

PMID- 24735564
TI  - Transmission blocking activity of Azadirachta indica and Guiera senegalensis
      extracts on the sporogonic development of Plasmodium falciparum field isolates in
      Anopheles coluzzii mosquitoes.
AB  - BACKGROUND: Targeting the stages of the malaria parasites responsible for
      transmission from the human host to the mosquito vector is a key pharmacological
      strategy for malaria control. Research efforts to identify compounds that are
      active against these stages have significantly increased in recent years.
      However, at present, only two drugs are available, namely primaquine and
      artesunate, which reportedly act on late stage gametocytes. METHODS: In this
      study, we assessed the antiplasmodial effects of 5 extracts obtained from the
      neem tree Azadirachta indica and Guiera senegalensis against the early vector
      stages of Plasmodium falciparum, using field isolates. In an ex vivo assay
      gametocytaemic blood was supplemented with the plant extracts and offered to
      Anopheles coluzzii females by membrane feeding. Transmission blocking activity
      was evaluated by assessing oocyst prevalence and density on the mosquito midguts.
      RESULTS: Initial screening of the 5 plant extracts at 250 ppm revealed
      transmission blocking activity in two neem preparations. Up to a concentration of
      70 ppm the commercial extract NeemAzal completely blocked transmission and at 60
      ppm mosquitoes of 4 out of 5 replicate groups remained uninfected. Mosquitoes fed
      on the ethyl acetate phase of neem leaves at 250 ppm showed a reduction in oocyst
      prevalence of 59.0% (CI95 12.0 - 79.0; p < 10-4) and in oocyst density of 90.5%
      (CI95 86.0 - 93.5; p < 10-4 ), while the ethanol extract from the same plant part
      did not exhibit any activity. No evidence of transmission blocking activity was
      found using G. senegalensis ethyl acetate extract from stem galls. CONCLUSIONS:
      The results of this study highlight the potential of antimalarial plants for the
      discovery of novel transmission blocking molecules, and open up the potential of
      developing standardized transmission blocking herbal formulations as malaria
      control tools to complement currently used antimalarial drugs and combination
      treatments.

PMID- 24735565
TI  - Protective effects of remote ischemic conditioning against ischemia/reperfusion
      induced retinal injury in rats.
AB  - Limb remote ischemic conditioning (LRIC) provides a physiologic strategy for
      harnessing the body's endogenous protective capabilities against injury induced
      by ischemia-reperfusion in the central nervous system. The aim of the present
      study was to determine if LRIC played a role in protecting the retina from
      ischemia-reperfusion injury. A total of 81 adult male Sprague-Dawley rats were
      randomly assigned to sham and ischemia/reperfusion with or without remote LRIC
      arms. The retinal ischemic model was generated through right middle cerebral
      artery occlusion (MCAO) and pterygopalatine artery occlusion for 60 min followed
      by 1, 3, and 7 days of subsequent reperfusion. LRIC was conducted immediately
      following MCAO by tightening a tourniquet around the upper thigh and releasing
      for three cycles. Paraffin sections were stained with hematoxylin and eosin in
      order to quantify the number of cells in retinal ganglion cells (RGCs) layer
      throughout the duration of the study. Cellular expression of glial fibrillary
      acidic protein (GFAP) was detected and examined through immunohistochemistry.
      Protein expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme
      oxygenase-1 (HO-1) was also analyzed by Western blot techniques. Our study
      demonstrated that the loss of cells in RGC layer was attenuated by LRIC treatment
      at 3 and 7 days following reperfusion (P < 0.05). Immunohistochemistry studies
      depicted a gradual increase (P < 0.05) in GFAP levels from day 1 through day 7
      following ischemia and subsequent reperfusion, whereas LRIC reduced GFAP levels
      at 1, 3, and 7 days postreperfusion. In addition, LRIC increased the expression
      of Nrf2 and HO-1 at day 1 and 3 following ischemia/reperfusion. This particular
      study is the first remote conditioning study applicable to retinal ischemia. Our
      results strongly support the position that LRIC may be used as a noninvasive
      neuroprotective strategy, which provides retinal protection from ischemia
      reperfusion injury through the upregulation of antioxidative stress proteins,
      such as Nrf2 and HO-1. 

PMID- 24735566
TI  - Histological and histometrical study of the protective role of alpha-tocopherol
      against sodium arsenite toxicity in rat ovaries.
AB  - This study examines histometrical changes induced by sodium arsenite (SA), as an
      environmental pollutant, and investigates the protective effect of alpha
      tocopherol on ovaries of SA-treated rats during the prenatal stage until sexual
      maturity. Rats were classified into groups: control, SA (8 ppm/day), alpha
      tocopherol (100 ppm/day), and SA+alpha-tocopherol. Treatment was performed from
      pregnancy until maturation when the rats and ovaries were weighed. The Cavalieri
      method was used to estimate volume of the ovaries, cortex, medulla, and corpus
      luteum. The mean diameter of oocytes, granulosa cells, and nuclei were measured
      and volume was estimated using the Nucleator method. The number of oocytes and
      thickness of the zona pellucida (ZP) were determined using an optical dissector
      and orthogonal intercept method, respectively. SA reduced the body and ovary
      weight, the number of secondary, antral and Graafian oocytes, volume of the
      ovaries, cortex, medulla and corpus luteum, mean diameter and volume of oocytes
      in primordial and primary follicles, mean diameter and volume of oocyte nuclei in
      all types of follicles, and mean thickness of the ZP in secondary and antral
      follicles. Also, the mean diameter and volume of granulosa cells and their nuclei
      in antral and Graafian follicles decreased significantly. Vacuolization and
      vascular congestion in the corpus luteum and an increase in the number of atretic
      oocytes were seen in the SA group. Most of these parameters were unchanged from
      the control level in the SA+alpha-tocopherol group. It was concluded that alpha
      tocopherol supplementation reduced the toxic effects of SA exposure on ovarian
      tissue in rats. 

PMID- 24735567
TI  - Factors related to sustained use of a free mobile app for dietary self-monitoring
      with photography and peer feedback: retrospective cohort study.
AB  - BACKGROUND: Healthy eating interventions that use behavior change techniques such
      as self-monitoring and feedback have been associated with stronger effects.
      Mobile apps can make dietary self-monitoring easy with photography and
      potentially reach huge populations. OBJECTIVE: The aim of the study was to assess
      the factors related to sustained use of a free mobile app ("The Eatery") that
      promotes healthy eating through photographic dietary self-monitoring and peer
      feedback. METHODS: A retrospective analysis was conducted on the sample of
      189,770 people who had downloaded the app and used it at least once between
      October 2011 and April 2012. Adherence was defined based on frequency and
      duration of self-monitoring. People who had taken more than one picture were
      classified as "Users" and people with one or no pictures as "Dropouts". Users who
      had taken at least 10 pictures and used the app for at least one week were
      classified as "Actives", Users with 2-9 pictures as "Semi-actives", and Dropouts
      with one picture as "Non-actives". The associations between adherence,
      registration time, dietary preferences, and peer feedback were examined. Changes
      in healthiness ratings over time were analyzed among Actives. RESULTS: Overall
      adherence was low-only 2.58% (4895/189,770) used the app actively. The day of
      week and time of day the app was initially used was associated with adherence,
      where 20.28% (5237/25,820) of Users had started using the app during the daytime
      on weekdays, in comparison to 15.34% (24,718/161,113) of Dropouts. Users with
      strict diets were more likely to be Active (14.31%, 900/6291) than those who had
      not defined any diet (3.99%, 742/18,590), said they ate everything (9.47%,
      3040/32,090), or reported some other diet (11.85%, 213/1798) (chi(2) 3=826.6,
      P<.001). The average healthiness rating from peers for the first picture was
      higher for Active users (0.55) than for Semi-actives (0.52) or Non-actives (0.49)
      (F2,58167=225.9, P<.001). Actives wrote more often a textual description for the
      first picture than Semi-actives or Non-actives (chi(2) 2=3515.1, P<.001).
      Feedback beyond ratings was relatively infrequent: 3.83% (15,247/398,228) of
      pictures received comments and 15.39% (61,299/398,228) received "likes" from
      other users. Actives were more likely to have at least one comment or one "like"
      for their pictures than Semi-actives or Non-actives (chi(2) 2=343.6, P<.001, and
      chi(2) 2=909.6, P<.001, respectively). Only 9.89% (481/4863) of Active users had
      a positive trend in their average healthiness ratings. CONCLUSIONS: Most people
      who tried out this free mobile app for dietary self-monitoring did not continue
      using it actively and those who did may already have been healthy eaters. Hence,
      the societal impact of such apps may remain small if they fail to reach those who
      would be most in need of dietary changes. Incorporating additional self
      regulation techniques such as goal-setting and intention formation into the app
      could potentially increase user engagement and promote sustained use.

PMID- 24735568
TI  - Performance on a pattern separation task by Alzheimer's patients shows possible
      links between disrupted dentate gyrus activity and apolipoprotein E ?4 status and
      cerebrospinal fluid amyloid-beta42 levels.
AB  - INTRODUCTION: Emerging evidence suggests that decreased adult hippocampal
      neurogenesis represents an early critical event in the course of Alzheimer's
      disease (AD). In mice, adult neurogenesis is reduced by knock-in alleles for
      human apolipoprotein E (ApoE) ?4. Decreased dentate gyrus (DG) neural progenitor
      cells proliferation has been observed in the triple-transgenic mouse model of AD
      (3xTg-AD); this reduction being directly associated with the presence of amyloid
      beta (Abeta) plaques and an increase in the number of Abeta-containing neurons in
      the hippocampus. Cognitive tasks involving difficult pattern separations have
      been shown to reflect DG activity and thus potentially neurogenesis in both
      animals and man. This study involved the administration of a pattern separation
      paradigm to Alzheimer's patients to investigate relationships between task
      performance and both ApoE status and cerebrospinal fluid (CSF) Abeta42 levels.
      METHODS: The CDR System pattern separation task involves the presentation of
      pictures that must later be discriminated from closely similar pictures. This
      paper presents pattern separation data from 66 mild to moderate AD patients, of
      which 50 were genotyped and 65 in whom CSF Abeta42 was measured. RESULTS: ApoE ?4
      homozygotes were not compromised on the easy pattern separations compared with
      the other patients, but they were statistically significantly poorer at the
      difficult separations. In all patients CSF Abeta42 correlated significantly with
      the ability to make the difficult discriminations, but not easier
      discriminations. Pattern separation speed correlated negatively with CSF Abeta42,
      and thus the association was not due to increased impulsivity. CONCLUSIONS: These
      are, to our knowledge, the first human pattern separation data to suggest a
      possible genetic link to poor hippocampal neurogenesis in AD, as well as a
      relationship to Abeta42. Therapies which target neurogenesis may thus be useful
      in preventing the early stages of AD, notably in ApoE ?4 homocygotes.

PMID- 24735569
TI  - Hematology and plasma biochemistry of wild-caught Indian cobra Naja naja
      (Linnaeus, 1758).
AB  - BACKGROUND: Hematology and plasma biochemistry parameters are useful in the
      assessment and management of snake physiological status. Although reference
      ranges are readily available for many snake species, they are lacking for most
      venomous ophidians. We determined hematology and plasma biochemistry reference
      ranges for the wild-caught Indian cobra, Naja naja. RESULTS: Blood samples, taken
      from the ventral tail vein, were assessed for erythrocyte count, total leukocyte
      count, hemoglobin concentration, hematocrit, mean corpuscular volume, mean
      corpuscular hemoglobin, and mean corpuscular hemoglobin concentration,
      considering the sex of snakes. Results revealed the erythrocyte numbers (male,
      390000 +/- 12503.33/mm(3) and female, 347500 +/- 7505.55/mm(3)), shapes and the
      centrally located oval nuclei. Leukocytes were round, circular or disk-shaped,
      and the mean size was larger in male than female snakes. The maximum number of
      leukocytes was found to be 11700 +/- 100/mm(3) in male and 12100 +/- 200/mm(3) in
      female snakes, and mean values of differential leukocyte count differed
      statistically between male and female snakes. The total leukocyte levels were
      found to be higher in female snakes, but the levels of hemoglobin, hematocrit,
      and MCV values were higher in male snakes. However, the MCH and MCHC values
      remained higher in female snakes throughout the study period. Mean protein and
      cholesterol contents differed significantly between male (45.32 +/- 1.76 and 3.76
      +/- 0.06 mg/mL) and female (12.47 +/- 0.82 and 4.72 +/- 0.2 mg/mL) snakes.
      CONCLUSIONS: In conclusion, monitoring snake hematological and biochemical
      parameters can serve as a means to evaluate the physiological and health status
      of N. naja populations, which may be a useful indicator of their environmental
      status.

PMID- 24735571
TI  - Mandated ultrasound prior to abortion.

PMID- 24735570
TI  - Loneliness and health risk behaviours among Russian and U.S. adolescents: a cross
      sectional study.
AB  - BACKGROUND: For some adolescents feeling lonely can be a protracted and painful
      experience. It has been suggested that engaging in health risk behaviours such as
      substance use and sexual behaviour may be a way of coping with the distress
      arising from loneliness during adolescence. However, the association between
      loneliness and health risk behaviour has been little studied to date. To address
      this research gap, the current study examined this relation among Russian and
      U.S. adolescents. METHODS: Data were used from the Social and Health Assessment
      (SAHA), a school-based survey conducted in 2003. A total of 1995 Russian and 2050
      U.S. students aged 13-15 years old were included in the analysis. Logistic
      regression was used to examine the association between loneliness and substance
      use, sexual risk behaviour, and violence. RESULTS: After adjusting for
      demographic characteristics and depressive symptoms, loneliness was associated
      with a significantly increased risk of adolescent substance use in both Russia
      and the United States. Lonely Russian girls were significantly more likely to
      have used marijuana (odds ratio [OR]: 2.28; confidence interval [CI]: 1.17-4.45),
      while lonely Russian boys had higher odds for past 30-day smoking (OR, 1.87; CI,
      1.08-3.24). In the U.S. loneliness was associated with the lifetime use of
      illicit drugs (excepting marijuana) among boys (OR, 3.09; CI, 1.41-6.77) and with
      lifetime marijuana use (OR, 1.79; CI, 1.26-2.55), past 30-day alcohol consumption
      (OR, 1.80; CI, 1.18-2.75) and past 30-day binge drinking (OR, 2.40; CI, 1.56
      3.70) among girls. The only relation between loneliness and sexual risk behaviour
      was among Russian girls, where loneliness was associated with significantly
      higher odds for ever having been pregnant (OR, 1.69; CI: 1.12-2.54). Loneliness
      was not associated with violent behaviour among boys or girls in either country.
      CONCLUSION: Loneliness is associated with adolescent health risk behaviour among
      boys and girls in both Russia and the United States. Further research is now
      needed in both settings using quantitative and qualitative methods to better
      understand the association between loneliness and health risk behaviours so that
      effective interventions can be designed and implemented to mitigate loneliness
      and its effects on adolescent well-being.

PMID- 24735572
TI  - Drug samples: why not?

PMID- 24735573
TI  - Is parental smoking neglect of an asthmatic child?

PMID- 24735574
TI  - Legislating abortion care.

PMID- 24735575
TI  - The benefits of online health communities.

PMID- 24735576
TI  - Professional self-regulation in medicine.

PMID- 24735577
TI  - OxyContin, the FDA, and Drug Control.

PMID- 24735578
TI  - Physician "gag laws" and gun safety.

PMID- 24735579
TI  - Consent and rights in comparative effectiveness trials.

PMID- 24735580
TI  - Inappropriate obstructions to access: the FDA's handling of plan B.

PMID- 24735581
TI  - American society for reproductive medicine updates consent forms for egg
      donation.

PMID- 24735582
TI  - Decision on mandating coverage for ART must begin with accurate data.

PMID- 24735583
TI  - Spatial distribution of malaria in Peninsular Malaysia from 2000 to 2009.
AB  - BACKGROUND: Malaria is still an endemic disease of public health importance in
      Malaysia. Populations at risk of contracting malaria includes indigenous people,
      traditional villagers, mobile ethnic groups and land scheme settlers, immigrants
      from malaria endemic countries as well as jungle workers and loggers. The
      predominant species are Plasmodium falciparum and P. vivax. An increasing number
      of P. knowlesi infections have also been encountered. The principal vectors in
      Peninsular Malaysia are Anopheles maculatus and An. cracens. This study aims to
      determine the changes in spatial distribution of malaria in Peninsular Malaysia
      from year 2000-2009. METHODS: Data for the study was collected from Ministry of
      Health, Malaysia and was analysed using Geographic Information System (GIS).
      RESULTS: Changes for a period of 10 years of malaria spatial distribution in 12
      states of Peninsular Malaysia were documented and discussed. This is illustrated
      by digital mapping according to five variables; incidence rate (IR), fatality
      rate (FR), annual blood examination rate (ABER), annual parasite index (API) and
      slide positivity rate (SPR). CONCLUSION: There is a profound change in the
      spatial distribution of malaria within a 10-year period. This is evident from the
      digital mapping of the infection in Peninsular Malaysia.

PMID- 24735584
TI  - Lectin uptake and incorporation into the calcitic spicule of sea urchin embryos.
AB  - Primary mesenchyme cells (PMCs) are skeletogenenic cells that produce a
      calcareous endoskeleton in developing sea urchin larvae. The PMCs fuse to form a
      cavity in which spicule matrix proteins and calcium are secreted forming the
      mineralized spicule. In this study, living sea urchin embryos were stained with
      fluorescently conjugated wheat germ agglutinin, a lectin that preferentially
      binds to PMCs, and the redistribution of this fluorescent tag was examined during
      sea urchin development. Initially, fluorescence was associated primarily with the
      surface of PMCs. Subsequently, the fluorescent label redistributed to
      intracellular vesicles in the PMCs. As the larval skeleton developed,
      intracellular granular staining diminished and fluorescence appeared in the
      spicules. Spicules that were cleaned to remove membranous material associated
      with the surface exhibited bright fluorescence, which indicated that
      fluorescently labelled lectin had been incorporated into the spicule matrix. The
      results provide evidence for a cellular pathway in which material is taken up at
      the cell surface, sequestered in intracellular vesicles and then incorporated
      into the developing spicule. 

PMID- 24735585
TI  - Methionine sulfoxide reductase regulates brain catechol-O-methyl transferase
      activity.
AB  - Catechol-O-methyl transferase (COMT) plays a key role in the degradation of brain
      dopamine (DA). Specifically, low COMT activity results in higher DA levels in the
      prefrontal cortex (PFC), thereby reducing the vulnerability for attentional and
      cognitive deficits in both psychotic and healthy individuals. COMT activity is
      markedly reduced by a non-synonymous single-nucleotide polymorphism (SNP) that
      generates a valine-to-methionine substitution on the residue 108/158, by means of
      as-yet incompletely understood post-translational mechanisms. One post
      translational modification is methionine sulfoxide, which can be reduced by the
      methionine sulfoxide reductase (Msr) A and B enzymes. We used recombinant COMT
      proteins (Val/Met108) and mice (wild-type (WT) and MsrA knockout) to determine
      the effect of methionine oxidation on COMT activity and COMT interaction with
      Msr, through a combination of enzymatic activity and Western blot assays.
      Recombinant COMT activity is positively regulated by MsrA, especially under
      oxidative conditions, whereas brains of MsrA knockout mice exhibited lower COMT
      activity (as compared with their WT counterparts). These results suggest that
      COMT activity may be reduced by methionine oxidation, and point to Msr as a key
      molecular determinant for the modulation of COMT activity in the brain. The role
      of Msr in modulating cognitive functions in healthy individuals and schizophrenia
      patients is yet to be determined. 

PMID- 24735586
TI  - High levels of memory B cells are associated with response to a first tumor
      necrosis factor inhibitor in patients with rheumatoid arthritis in a longitudinal
      prospective study.
AB  - INTRODUCTION: Tumor necrosis factor inhibitor (TNFi) therapy is effective for
      rheumatoid arthritis (RA). Some researchers have suggested that TNFi therapy
      affects B-cell homeostasis. We studied the effect of TNFi therapy on the
      distribution of peripheral B-cell subsets to elucidate B-cell-related biomarkers
      to predict the TNFi response. METHODS: Peripheral B cells were analyzed for
      expression of CD19, CD27, CD38 and immunoglobulin D in 31 healthy donors and 96
      RA patients, including 21 patients who were followed 3 months after TNFi
      initiation. RESULTS: Treatment with steroids significantly altered the
      distribution of B-cell subsets. After we adjusted for age, sex and steroid dose,
      we found that patients with RA had B-cell subset proportions similar to controls.
      B-cell subset distributions did not differ upon use of TNFi at baseline or before
      or after TNFi introduction. TNFi responders (according to European League Against
      Rheumatism criteria) at 3 months had significantly higher proportions of CD27+
      memory B cells at baseline, and >=26% CD27+ cells at inclusion was associated
      with a relative risk of 4.9 (1.3 to 18.6) for response to TNFi treatment. CD27+
      cells produced three times more TNFalpha than did TNFi-naive B cells and were
      correlated with interferon gamma produced from CD4+ cells in patients without
      TNFi treatment. CONCLUSIONS: In patients with RA, high levels of baseline memory
      B cells were associated with response to TNFi, which may be related to TNFalpha
      dependent activation of the T helper type 1 cell pathway.

PMID- 24735587
TI  - Nasogastric tube placement and verification in children: review of the current
      literature.
AB  - Placement of a nasogastric enteral access device (NG-EAD), often referred to as a
      nasogastric tube, is common practice and largely in the domain of nursing care.
      Most often an NG-EAD is placed at the bedside without radiographic assistance.
      Correct initial placement and ongoing location verification are the primary
      challenges surrounding NG-EAD use and have implications for patient safety.
      Although considered an innocuous procedure, placement of an NG-EAD carries risk
      of serious and potentially lethal complications. Despite acknowledgment that an
      abdominal radiograph is the gold standard, other methods of verifying placement
      location are widely used and have success rates from 80% to 85%. The long
      standing challenges surrounding bedside placement of NG-EADs and a practice alert
      issued by the Child Health Patient Safety Organization on this issue were the
      stimuli for the conception of The New Opportunities for Verification of Enteral
      Tube Location Project sponsored by the American Society for Parenteral and
      Enteral Nutrition. Its mission is to identify and promote best practices with the
      potential of technology development that will enable accurate determination of NG
      EAD placement for both the inpatient and outpatient pediatric populations. This
      article presents the challenges of bedside NG-EAD placement and ongoing location
      verification in children through an overview of the current state of the science.
      It is important for all health care professionals to be knowledgeable about the
      current literature, to be vigilant for possible complications, and to avoid
      complacency with NG-EAD placement and ongoing verification of tube location. 

PMID- 24735588
TI  - The effect of a pre- and postoperative orthogeriatric service on cognitive
      function in patients with hip fracture: randomized controlled trial (Oslo
      Orthogeriatric Trial).
AB  - BACKGROUND: Delirium is a common complication in patients with hip fractures and
      is associated with an increased risk of subsequent dementia. The aim of this
      trial was to evaluate the effect of a pre- and postoperative orthogeriatric
      service on the prevention of delirium and longer-term cognitive decline. METHODS:
      This was a single-center, prospective, randomized controlled trial in which
      patients with hip fracture were randomized to treatment in an acute geriatric
      ward or standard orthopedic ward. Inclusion and randomization took place in the
      Emergency Department at Oslo University hospital. The key intervention in the
      acute geriatric ward was Comprehensive Geriatric Assessment including daily
      interdisciplinary meetings. Primary outcome was cognitive function four months
      after surgery measured using a composite outcome incorporating the Clinical
      Dementia Rating Scale (CDR) and the 10 words learning and recalls tasks from the
      Consortium to Establish a Registry for Alzheimer's Disease battery (CERAD).
      Secondary outcomes were pre- and postoperative delirium, delirium severity and
      duration, mortality and mobility (measured by the Short Physical Performance
      Battery (SPPB)). Patients were assessed four and twelve months after surgery by
      evaluators blind to allocation. RESULTS: A total of 329 patients were included.
      There was no significant difference in cognitive function four months after
      surgery between patients treated in the acute geriatric and the orthopedic wards
      (mean 54.7 versus 52.9, 95% confidence interval for the difference -5.9 to 9.5; P
      = 0.65). There was also no significant difference in delirium rates (49% versus
      53%, P = 0.51) or four month mortality (17% versus 15%, P = 0.50) between the
      intervention and the control group. In a pre-planned sub-group analysis,
      participants living in their own home at baseline who were randomized to
      orthogeriatric care had better mobility four months after surgery compared with
      patients randomized to the orthopedic ward, measured with SPPB (median 6 versus
      4, 95% confidence interval for the median difference 0 to 2; P = 0.04).
      CONCLUSIONS: Pre- and postoperative orthogeriatric care given in an acute
      geriatric ward was not effective in reducing delirium or long-term cognitive
      impairment in patients with hip fracture. The intervention had, however, a
      positive effect on mobility in patients not admitted from nursing homes. TRIAL
      REGISTRATION: ClinicalTrials.gov NCT01009268 Registered November 5, 2009.

PMID- 24735589
TI  - Antiretroviral drug expenditure, pricing and judicial demand: an analysis of
      federal procurement data in Brazil from 2004-2011.
AB  - BACKGROUND: Previous studies have described expenditures for antiretroviral (ARV)
      medicines in Brazil through 2005. While prior studies examined overall
      expenditures, they have not have analyzed drug procurement data in order to
      describe the role of court litigation on access and pricing. METHODS: ARV drug
      procurement from private sector sources for the years 2004-2011 was obtained
      through the general procurement database of the Brazilian Federal Government
      (SIASG). Procurement was measured in Defined Daily Doses (DDD) per 1000 persons
      under-treatment per day. Expenditures and price per DDD were calculated and
      expressed in U.S. Dollars. Justifications for ARV purchases were examined in
      order to determine the relationship between health litigation and incorporation
      into Brazil's national treatment guidelines. RESULTS: Drug procurement of ARVs
      from private sources underwent marked expansion in 2005, peaked in 2009, and
      stabilized to 2008 levels by 2011. Expenditures followed procurement curves.
      Medications which were procured for the first time after 2007 cost more than
      medicines which were introduced before 2007. Judicial actions initially resulted
      in purchases of newer medications for a select number of patients in Brazil but
      ultimately expanded availability to a larger population through incorporation
      into the national treatment guidelines. CONCLUSIONS: Drug procurement and
      expenditures for ARVs in Brazil varied between 2004-2011. The procurement of some
      drugs from the private sector ceased after public manufacturers started producing
      them locally. Judicial demand has resulted in the incorporation of newer drugs
      into the national treatment guidelines. In order for the AIDS treatment program
      to remain sustainable, efforts should be pursued to reduce prices through generic
      drugs, price negotiation and other public health flexibilities such as compulsory
      licensing.

PMID- 24735591
TI  - [Gut flora and gut-derived endotoxin in minimal hepatic encephalopathy].
AB  - OBJECTIVE: To investigate the relationship of gut flora and gut-derived endotoxin
      with minimal hepatic encephalopathy (MHE). METHODS: Patients with hepatitis B
      virus-related liver cirrhosis (HBV-LC) were screened for MHE using the number
      connect test-A (NCT-A) and digital symbol test (DST) and divided into the
      following groups: HBV-LC with (+) MHE (n = 26) and HBV-liver cirrhosis without (
      ) MHE (n = 25); in addition, one healthy immediate family member of each patient
      in the HBV-LC + MHE group was enrolled as a control. Each participant provided
      fecal and blood samples. PCR amplification and 454 pyrosequencing were used to
      detect bacterial 16S rRNA in feces. Turbidimetric Limulus amebocyte lysate assay
      was used to detect level of endotoxin in serum. The significance of inter-group
      differences was assessed by one-way ANOVA or Student's t-test. RESULTS: The three
      groups showed different distributions of gut flora. The differences in the
      microbial communities' members and distributions were related to disease or
      health status, but not to the patient's genetic makeup or diet. In particular,
      the HBV-LC + MHE patients showed significantly lower amounts of different
      bacterial species and abundance of these species than the other two (non-MHE)
      groups (P less than 0.05). The healthy control family members had a richer
      diversity of gut flora than their counterparts with HBV-LC + MHE (P less than
      0.05). The HBV-LV + MHE patients also had higher serum levels of endotoxin.
      CONCLUSION: Development of minimal hepatic encephalopathy in patients with HBV-LC
      may be related to a gut flora disorder or higher levels of endotoxin in serum.

PMID- 24735590
TI  - Screening and management of major bile leak after blunt liver trauma: a
      retrospective single center study.
AB  - BACKGROUND: Major bile leak after blunt liver trauma is rare but challenging. It
      usually requires endoscopic retrograde cholangiography (ERC) for management.
      However, there is still lack of specific indications. The aim of this study is to
      elucidate risk factors for major bile leak and indications for early ERC after
      blunt liver trauma. METHODS: The trauma registry of a level I trauma center in
      Taiwan was queried, and all blunt liver trauma patients from June, 2008 to June,
      2011 were selected for retrospective review. Data collected included demographic
      data, laboratory data, Injury Severity Score (ISS), liver injury grade and
      location, management of liver trauma, length of ICU, hospital stay and treatment
      result. ERC was used to confirm major bile leak. RESULTS: 288 blunt liver trauma
      patients were selected from 2,475 torso trauma patients. There were 214 (74.5%)
      male and 74 (25.7%) female patients. The mean ISS was 24.2. Most patients
      received conservative treatment. Transcatheter artery embolization (TAE) and
      operation were 15.6% and 10.8% respectively. Major bile leak occurred in 14
      (4.9%) patients. Risk factors for bile leak include high-grade liver injury,
      centrally-located liver trauma and use of TAE. A bilirubin level greater than
      43.6 MUmol/L provides a sensitivity of 100% and specificity of 85.1% for
      predicting major bile leak. CONCLUSIONS: High injury grade; centrally-located
      liver trauma; and use of TAE are risk factors for major bile leak after blunt
      liver trauma. ERC should be arranged early if the patient has risk factors and
      their plasma bilirubin level is greater than 43.6 MUmol/L during admission.

PMID- 24735592
TI  - [Meta-analysis of magnesium isoglycyrrhizinate combined with nucleoside analogues
      in patients with chronic hepatitis B].
AB  - OBJECTIVE: To evaluate the efficacy and safety of the magnesium
      isoglycyrrhizinate plus nucleoside analogues (MGL + NA) combination therapy in
      patients with chronic hepatitis B using a meta-analysis approach. METHODS: The
      Chinese Biochemical literature on Disc (CBMDisc) and the Chinese Scientific
      Journal database, CNKI, were searched for randomized controlled trials (RCTs) of
      MGL+NA in patients with chronic hepatitis B published between 1995 and 2013. Data
      related to treatment type (combination therapy vs. mono-therapy) and outcome
      (markers of efficacy and safety, including levels of hepatitis B virus (HBV) DNA,
      hepatitis B e antigen (HBeAg), alanine aminotransferase (ALT) and aspartate
      aminotransferase (AST)). Weighted mean differences (WMD) were calculated and the
      Peto method was used to determine the relative risk (RR), both with 95%
      confidence intervals (CIs). RESULTS: Meta-analysis of the six included RCTs of
      MGL + NA, representing a 704 patients with chronic hepatitis B, showed WMDs for
      ALT of -12.98 (95% CI: -18.24 to -7.71, P less than 0.01) and for AST of -9.49
      (95% CI: -14.53 to -4.45, P = 0.0002) and RRs for HBeAg of 1.79 (95% CI: 1.17 to
      2.76, P = 0.008) and for HBV DNA of 1.35 (95% CI: 1.05 to 1.74, P = 0.02). The
      therapeutic efficacy of MGL+NA combination therapy was better than that of NA
      mono-therapy (P less than 0.01). CONCLUSION: For patients with chronic hepatitis
      B, MGL combination therapy may enhance the antiviral efficacy of NA treatment and
      help to improve liver function during treatment.

PMID- 24735593
TI  - [Performance of FibroScan in evaluating the curative effects of traditional
      Chinese medicine on liver fibrosis].
AB  - OBJECTIVE: To assess the performance of FibroScan in evaluating the curative
      effects of traditional Chinese medicine (TCM) on liver fibrosis, and to analyze
      factors influencing the diagnostic accuracy. METHODS: Data of FibroScan values,
      types of disease, use of drug, liver function indexes, prothrombin time (PT) and
      international normalized ratio (INR) were collected at both pre- (1 month prior)
      and post-FibroScan for 102 patients who underwent at least two FibroScan
      procedures. Patients were subgrouped according to presence of fibrosis, presence
      of cirrhosis, and TCM formulation and statistically analyzed. RESULTS: The pre-
      and post-FibroScan mean liver stiffness measurements (LSMs) were significantly
      different when the variation of LSM was more than or equal to2 kPa for the non
      fibrotic group (vs. the fibrotic group), or when the variation wasmore than or
      equal to4 kPa for the cirrhotic group (vs. the non-cirrhotic group). In addition,
      the three TCM formulation groups showed significant differences, with the most
      robust difference exhibited between the FuZheng HuaYu formulation group and the
      other treatment groups (P = 0.010). No significant differences were observed for
      the liver function indexes, PT, or INR. However, the post-FibroScan levels of
      alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma
      glutamyltransferase (GGT) was significantly reduced in patients with reduced LSM.
      CONCLUSION: FibroScan may be a useful non-invasive clinical tool for evaluating
      the comprehensive curative effect of treatments for chronic liver diseases, and
      its performance is not obviously impacted by ALT, AST, GGT, PT, and INR. The
      criteria for efficacy established by FibroScan are 2 kPa for the patients without
      liver fibrosis and 4 kPa for patients with liver cirrhosis.

PMID- 24735594
TI  - [Differential expression in ACE2, Ang(1-7) and Mas receptor during progression of
      liver fibrosis in a rat model].
AB  - OBJECTIVE: To investigate the changes in expression of the ACE2/Ang(1-7)/Mas
      receptor axis' components that occur during progression of liver fibrosis using a
      rat model system. METHODS: Thirty-six adult male Wistar rats, were randomly
      assigned to groups of normal control (n = 6; no manipulation) and liver fibrosis
      (n = 30; given a subcutaneous injection of 40% chronic carbon tetrachloride
      (CCl4)). At post-injection days 15, 30, 45, 60 and 75, 1 control rat and 6
      modeled rats were sacrificed for analysis. Histopathological analysis of liver
      tissue was performed with hematoxylin-eosin and rapid Masson staining. Protein
      expression level of Ang(1-7) was determined by enzyme-linked immunosorbent assay,
      and of ACE2 and Mas receptor was evaluated by immunohistochemistry. Real-time PCR
      was used to measure the mRNA expression levels of ACE2 and Mas receptor. RESULTS:
      The expression levels of ACE2, Ang(1-7) and Mas receptor showed a statistically
      significant upward trend that followed the progression of fibrosis up to post
      injection day 60 (P less than 0.01), but the significant increase was not seen
      from day 60 to day 75. CONCLUSION: Each component of the ACE2/Ang(1-7)/Mas
      receptor axis shows differential expression during the development of liver
      fibrosis and may contribute to disease progression.

PMID- 24735595
TI  - [Mechanism and clinical significance of HBx-mediated inhibition of CYP2E1
      expression in the human HepG2 hepatoma cell line].
AB  - OBJECTIVE: To explore the mechanism of hepatitis B virus X protein (HBx)-mediated
      inhibition of CYP2El expression and its significance in hepatocellular carcinoma
      (HCC) metastasis. METHODS: A deletion series and mutagenesis series of human
      CYP2E1 promoter sequence was co-transfected with the HBx expression vector pCMV
      2B-FLAG-X into the human HepG2 hepatoma cell line. Reverse transcription-PCR and
      real-time PCR were used to evaluate the effects of HBx on CYP2E1 promoter
      activity. The luciferase reporter gene assay was used to identify the HBx
      responsive region in the CYP2E1 promoter. Electrophoretic mobility shift assay
      was used to detect the protein complexes binding to nucleic acids in the CYP2E1
      promoter. Martrigel invasion assay was used to examine effects of HBx-inhibited
      CYP2E1 on invasiveness. RESULTS: Analysis of the deletion series and mutagenesis
      series led to identification of two regions of sequence in the CYP2E1 promoter
      that are important in HBx-mediated modulation of CYP2E1 activity in HepG2 cells
      (F = 112.24, P = 0.001). Both HNF4alpha and SREBP-1, which directly interact with
      CYP2E1 promoter sequences, were implicated in the mechanism of HBx-mediated
      modulation of CYP2E1 promoter activity. In addition, PI3K and JNK pathways were
      involved in the HBx-mediated modulation (t = 8.56, P = 0.0012 and t = 10.25, P =
      0.0009 respectively). HBx-mediated repression of constitutive CYP2E1 led to
      increased invasiveness. CONCLUSION: HBx-mediated inhibition of CYP2E1 expression
      may promote HCC by increasing tumor progression and invasiveness through
      modulation of the PI3K and JNK signaling pathways.

PMID- 24735596
TI  - [Diagnosing radiation-induced liver injury in rabbit using 3.0 Tesla magnetic
      resonance diffusion-weighted imaging].
AB  - OBJECTIVE: To evaluate the clinical value of magnetic resonance (MR) diffusion
      weighted imaging (DWI) for diagnosing radiation-induced liver injury (RILI) and
      detecting changes in hepatic pathology at different post-irradiation times.
      METHODS: Male New Zealand white rabbits received no irradiation (C0, control
      group; n = 10) or irradiation of 50 Gy/10F once every other day by virtual three
      dimensional conformal radiotherapy (3D-CRT) for one day (C1; n = 10), three days
      (C2; n = 10), two weeks (C3; n = 10), one month (C4; n = 10) or two months (C5; n
      = 10). One member of all groups were sacrificed for DWI examination and
      pathologic study on post-irradiation day 1, day 3, week 2, month 1 and month 2.
      The apparent diffusion coefficient (ADC) values were measured using a range of b
      values (50, 300, 600, 800 and 1000 s/mm2). RESULTS: Hematoxylin-eosin (H-E)
      staining showed that livers of rabbits in the C3, C4 and C5 groups had the
      characteristic features of veno-occlusive disease. DWI examination showed that
      the irradiated livers of rabbits in C2, C3, C4 and C5 groups had significantly
      lower ADC values than the livers of the non-irradiated rabbits at b values of
      300, 600, 800 and 1000 s/mm2 (P less than 0.05). When the b value was 600 s/mm2,
      the best negative correlation between ADC values and pathological stage was seen
      for the irradiated livers (Spearman's rank, r = -0.459, P less than 0.01). The
      threshold ADC value to distinguish the normal group (C0) from an irradiated group
      (more than or equal toC1) was 1.955 * 10-3 mm2/s at 600 s/mm2 b value. When the b
      value was 1000 s/mm2, the threshold ADC value to predict an irradiated group with
      normal H-E staining (C1) from an irradiated group with abnormal H-E staining
      (more than or equal toC2) was 1.5250 * 10-3 mm2/s; the ADC threshold value was
      1.5150 * 10-3 mm2/s to predict groups C0-2 and groups C3-5. CONCLUSION: DWI has
      high sensitivity for detecting RILI at three days after irradiation with proper b
      values. Use of the ADC value is feasible for estimating the evolutionary process
      of pathological features of RILI damage. DWI may represent an important clinical
      tool for detection of early pathological changes in RILI.

PMID- 24735597
TI  - [Activation of hepatocyte growth factor promotes apoptosis of hepatic stellate
      cells via the Rho pathway].
AB  - OBJECTIVE: To investigate the role of activated hepatocyte growth factor (HGF) in
      apoptosis of hepatic stellate cells (HSCs) and in modulating the Rho signaling
      pathway. METHODS: HSCs were divided into the following groups: blank control,
      consisting of HSCs without treatment; two treatment controls, consisting of HSCs
      exposed to exogenous HGF at 50 ng/ml and HSCs exposed to exogenous HGF activator
      (HGFA) at 70 ng/ml; three experimental groups, consisting of HSCs exposed to both
      exogenous HGF and HGFA, HSCs pre-incubated with the HGF inhibitor c-met at 500
      ng/ml for 6 hours and then exposed to exogenous HGF and HGFA, and HSCs pre
      incubated with the Rho pathway inhibitor Y-27632 at 10 ng/ml and then exposed to
      exogenous HGF and HGFA. Activation status of the cultured HSCs was determined by
      change in expression of alpha-smooth muscle actin (SMA). The optimal intervention
      concentration of Y-27632 was determined by MTT assay. The apoptotic status of
      HSCs was determined by flow cytometry. Expression of the HGF-alpha chain was
      detected by immunofluorescence. The expression of RhoA was evaluated by PCR (for
      mRNA) and by immunohistochemical staining and Western blot analysis (for
      protein). RESULTS: Exposure to 10 mumol/L Y-27632 led to obvious growth
      inhibition of HGF + HGFA-induced HSCs, compared with the other concentrations
      tested (P less than 0.05). HGF + HGFA induced the expression of the HGF-alpha
      chain in a time-dependent manner (P less than 0.01); however, the increases in
      expression of HGF-alpha chain induced by HGF alone and HGFA alone were not
      significantly different from the level in the blank controls (P more than 0.05).
      Exposure to HGF alone and HGFA alone led to a time-dependent increase in
      apoptosis (24 h, 48 h, 72 h) but exposure to HGF + HGFA led to the highest levels
      of apoptosis (P less than 0.05). Exposure to HGF + HGFA led to a time-dependent
      decrease in RhoA mRNA and protein expression (P less than 0.01). CONCLUSION:
      Activation of hepatocyte growth factor promotes apoptosis of hepatic stellate
      cells by suppressing RhoA expression and down-regulating the Rho signaling
      pathway.

PMID- 24735598
TI  - [Preparation of a glypican-3-targeting hepatocellular carcinoma MR probe and its
      molecular imaging in HepG2 cells].
AB  - OBJECTIVE: To prepare a glypican-3 (GPC3)-targeting hepatocellular carcinoma MR
      molecular probe and to evaluate its targeting specificity using HepG2 cells.
      METHODS: Poly(lactic-co-glycolic acid) (PLGA) nanoparticles were prepared by a
      double emulsion solvent evaporation method, and the surfaces were connected with
      anti-GPC3 mono-antibody and paramagnetic substance Gd3+. The physical properties
      of the probes were investigated using fluorescence microscopy, electron
      microscopy, Malvern particle size analysis, inductively coupled plasma atomic
      emission spectroscopy (ICP-AES) and 1.5T MR imaging. The specificity of the
      probes to target cultured HepG2 cells was determined by laser confocal
      microscopy. The signal characteristics, including signal-to-noise ratio (SNR),
      after co-incubation with HepG2 cells were analyzed by 1.5T MR imaging.
      Significance of differences between multiple groups (target group, non-target
      group, and control group) was assessed by one-way analysis of variance, and
      between two groups was assessed by the LSD-t test. A difference was considered to
      be statistically significant at P less than 0.05. RESULTS: The GPC3-targeting
      hepatocellular carcinoma MR molecular probes were successfully prepared. The
      nanoparticles had a spherical shape, size of 495 +/- 17.5 nm, uniform size
      distribution, good dispersibility, no obvious aggregation, and could
      significantly increase the T1 signal. Using the ICP-AES measurement, 1 mol PLGA
      carried about 12 mol Gd3+, and as the Gd3+ concentration increased, the T1 signal
      increased. The prepared MR molecular probes could specifically target HepG2
      cells, and could increase the T1 signal. The SNR value of the target group was
      3.45 +/- 0.21, of the non-target group was 1.43 +/- 0.07, and of the control
      group was 1.12 +/- 0.03. The SNR value of the target group was significantly
      higher than that of the non-target group and the control group (P less than
      0.05); there was no significant difference between the non-target group and the
      control group (P more than 0.05). CONCLUSION: PLGA nanoparticles, anti-GPC3 mono
      antibody and paramagnetic Gd3+ can be used to successfully prepare GPC3-targeting
      hepatocellular carcinoma MR molecular probes which are capable of specifically
      targeting HepG2 cells in vitro and being detected by 1.5T MR imaging. These MR
      molecular probes may represent a useful noninvasive imaging method for detecting
      early hepatocellular carcinoma in vivo.

PMID- 24735599
TI  - Development of a blocking ELISA for detection of antibodies against avian
      hepatitis E virus.
AB  - A blocking enzyme-linked immunosorbent assay (bELISA) was developed for the
      detection of immunoglobulin G antibodies against avian hepatitis E virus (HEV).
      In the bELISA, the coating antigen was a truncated protein containing C-terminal
      268-amino acid region of ORF2 from an avian HEV strain isolated in China (CaHEV)
      and blocking antibody was a monoclonal antibody (mAb) 1H5 recognizing the epitope
      within amino acids 384-414 in the C-terminal 268-amino acid region. The
      concentration of blocking mAb 1H5 was determined as that yielded an OD450nm value
      of 1.0 for binding to the coating antigen and the antigen concentration and serum
      dilution were optimized using a checkerboard titration. A cut-off value of 20.7%
      at the mean percent inhibition plus 3 standard deviations was determined by
      testing 265 negative sera. The bELISA had a sensitivity of 98.3% by testing 116
      positive sera from chickens infected experimentally with CaHEV and had no cross
      reaction with other anti-avian virus antibodies. The compliance rates of the
      bELISA with indirect ELISA and Western blot were 83.7% and 93.3%, respectively,
      by testing 300 field chicken sera. These results suggested that the bELISA
      developed in this study can be used for detection of antibodies against avian HEV
      and showed high reproducibility compared with indirect ELISA and Western blot
      methods. 

PMID- 24735600
TI  - Associations of epithelial sodium channel genes with blood pressure changes and
      hypertension incidence: the GenSalt study.
AB  - BACKGROUND: We examined the associations of epithelial sodium channel (ENaC)
      genes with blood pressure (BP) changes and hypertension incidence in a
      longitudinal family study. METHODS: A total of 2,755 Han Chinese participants of
      the Genetic Epidemiology Network of Salt Sensitivity (GenSalt) baseline
      examination were eligible for this study. The associations of 43 tag single
      nucleotide polymorphisms (SNPs) in ENaC genes with BP changes and hypertension
      incidence were assessed using mixed models to account for the correlations of
      repeated measures among individuals and within families. A genotype by time
      interaction term was used to model differences in longitudinal BP change
      according to genotype over time. Gene-based analyses were conducted using the
      truncated product method. The Bonferroni method was used to adjust for multiple
      testing in all analyses. RESULTS: During an average of 7.4 years follow-up,
      systolic BP (SBP) and diastolic BP (DBP) increased, and approximately 33% of
      participants developed hypertension. SCNN1A SNP rs11064153 and SCNN1G SNP
      rs4401050 were significantly associated with longitudinal changes in SBP after
      adjustment for multiple testing (P interaction = 5.8*10(-4) and 0.001,
      respectively). Similar but nonsignificant trends were observed for the
      associations between both rs11064153 and rs4401050 and DBP changes (P interaction
      = 0.024 and 0.005, respectively) and between rs11604153 and hypertension
      incidence (P = 0.02). Gene-based analyses also supported the overall association
      of SCNN1G with longitudinal changes in SBP (P = 2.0*10(-4)). CONCLUSIONS: Our
      findings indicated that SCNN1A and SCNN1G may contribute to BP changes over time
      in the Han Chinese population. Replication of these findings is warranted.

PMID- 24735602
TI  - Band broadening along gradient reversed phase columns: a potential gain in
      resolution factor.
AB  - The advantages of using columns packed with stationary phases having a
      composition gradient so that retention factors increase toward the outlet and
      eluting them with an isocratic mobile phase may provide increased peak resolution
      in liquid chromatography. This approach is discussed from a theoretical
      viewpoint. The retention factor is assumed to increase linearly along the column.
      The peak width can be predicted under three different conditions: (1) the
      possible band compression is neglected (the Giddings model); (2) band compression
      is taken into account (the Poppe model); and (3) both band compression and extra
      column effects are considered in the calculations. The impact of a stationary
      phase gradient on the resolution of a pair of compound difficult to separate
      (constant selectivity alpha=1.05) is illustrated for a 3mm*100mm silica
      monolithic column of the second generation (porosity epsilont=0.85, plate height
      H=6MUm) operated with a new generation of liquid chromatograph (pre- and post
      column volume variances of 10 and 5MUL(2), respectively). The results show that
      the resolution factor RS becomes optimum for a specific positive value of the
      retention gradient along the column. This optimum depends on the retention factor
      at the column inlet. 

PMID- 24735601
TI  - CXCL12 in astrocytes contributes to bone cancer pain through CXCR4-mediated
      neuronal sensitization and glial activation in rat spinal cord.
AB  - BACKGROUND: Previous studies have demonstrated that chemokine CXCL12 and its
      receptor CXCR4 are critical for pain sensitization, but the mechanisms involved
      are not clear. In this study, we investigated the specific cellular mechanisms of
      CXCL12/CXCR4 chemokine signaling in the development and maintenance of bone
      cancer pain after tumor cell implantation (TCI). METHODS: TCI in the tibial
      cavity of rats was used to establish a bone cancer pain model. Mechanical
      allodynia and thermal hyperalgesia were determined by measuring the paw
      withdrawal threshold and latency, respectively. The protein expression and
      cellular localization of CXCL12 and CXCR4 were detected by western blot and
      immunofluorescence staining. The sensitization of neurons, activation of
      astrocytes and microglia were examined by observing the immunofluorescence
      intensity of c-Fos, GFAP and IBA1. RESULTS: Our results demonstrated that CXCL12
      was upregulated in a time-related manner, both in the dorsal root ganglia and
      spinal cord after TCI. Spinal CXCL12 was predominately expressed in astrocytes,
      and an intrathecal injection of astrocyte metabolic inhibitor fluorocitrate or
      selective JNK inhibitor SP600125 abolished TCI-induced CXCL12 production. A
      single intrathecal injection of a CXCL12 neutralizing antibody (10 MUg/10 MUl) at
      day 10 after TCI transiently reversed bone cancer pain in a dose-dependent
      manner. Whereas repetitive intrathecal administration of a CXCL12 neutralizing
      antibody (10 MUg/10 MUl, once a day from day 3 to 5 after TCI) significantly
      delayed the onset of TCI-induced pain behaviors for nearly five days. Spinal
      CXCR4 was also upregulated after TCI and colocalized with neurons, astrocytes and
      microglia. Blocking CXCR4 suppressed TCI-induced activation of neurons,
      astrocytes and microglia in the spinal cord at day 14. Repeated intrathecal
      administration of AMD3100 (5 MUg/10 MUl, once a day for three days) significantly
      delayed and suppressed the initiation and persistence of bone cancer pain in the
      early phase (at day 5, 6 and 7 after TCI) and in the late phase (at day 12, 13
      and 14 after TCI) of bone cancer, respectively. CONCLUSIONS: Taken together,
      these results demonstrate that CXCL12/CXCR4 signaling contributed to the
      development and maintenance of bone cancer pain via sensitizing neurons and
      activating astrocytes and microglia. Additionally, this chemokine signaling may
      be a potential target for treating bone cancer pain.

PMID- 24735603
TI  - Antimicrobial potential of bacteriocin producing Lysinibacillus jx416856 against
      foodborne bacterial and fungal pathogens, isolated from fruits and vegetable
      waste.
AB  - In this study, antimicrobial potential, some probiotics properties and
      bacteriocin nature of Lysinibacillus, isolated from fruits and vegetable waste
      were evaluated. For this, 125 Lactobacillus isolates were tested against
      foodborne bacterial and fungal pathogens. Among these, an isolated Bacillus spp.
      showed significant aggregation-co-aggregation probiotics properties and
      potentially inhibits the foodborne gram positive microbial pathogens such as
      Staphylococcus aureus, (22 mm ZOI), Staphylococcus epedermidis and Bacillus
      cereus (18 mm). Phenotypically and molecularly it was identified as
      Lysinibacillus (NCBI accession no. JX416856) and it was found closest to
      Lysinibacillus fusiformis, Lysinibacillus sphaericus and Lysinibacillus
      xylanilyticus. Physico-biochemically, it was found to be negative for amylase,
      protease, gelatinase, nitrate reductase and urease while positive for catalase.
      The diagnostic fatty acid was 22;2 (3.51). The growth conditions and bacteriocin
      activity were found to be optimum with MRS media at pH 7-10, Temperature 35-40 
      degrees C and salt tolerance at 1-3%. Eventually its production was optimized
      with MRS broth at pH 7.6, 37  degrees C, for 36 h in shaking conditions at the
      rate of 100 rpm. Active bacteriocin was isolated at 60% ammonium sulfate
      precipitation. The molecular weight of given bacteriocin was found to be nearly
      25-35 kDa by SDS-PAGE. Based on physico- biochemical properties, the isolated
      bacteriocin was to be categories in class II bacteriocin. The bacteriocin was
      found to be stable in the range of 4-80  degrees C temperature, 6-10 pH and even
      in the presence of surfactant (such as SDS and Tween 80). However, proteases like
      pepsin and trypsin were found to degrade the bacteriocin. Collectively, the broad
      spectrum inhibitory potential and physical stability offered the antimicrobial
      potential to Lysinibacillus, and its relevant bacteriocin might be used as an
      alternative food preservative or therapeutic agent to control spoilage of
      different food products. 

PMID- 24735604
TI  - De novo dominant mutation of SOX10 gene in a Chinese family with Waardenburg
      syndrome type II.
AB  - OBJECTIVE: Waardenburg syndrome is a rare genetic disorder, inherited as an
      autosomal dominant trait. The condition is characterized by sensorineural hearing
      loss and pigment disturbances of the hair, skin, and iris. The de novo mutation
      in the SOX10 gene, responsible for Waardenburg syndrome type II, is rarely seen.
      The present study aimed to identify the genetic causes of Waardenburg syndrome
      type II in a Chinese family. METHODS: Clinical and molecular evaluations were
      conducted in a Chinese family with Waardenburg syndrome type II. RESULTS: A novel
      SOX10 heterozygous c.259-260delCT mutation was identified. Heterozygosity was not
      observed in the parents and sister of the proband, indicating that the mutation
      has arisen de novo. The novel frameshift mutation, located in exon 3 of the SOX10
      gene, disrupted normal amino acid coding from Leu87, leading to premature
      termination at nucleotide 396 (TGA). The high mobility group domain of SOX10 was
      inferred to be partially impaired. CONCLUSION: The novel heterozygous c.259
      260delCT mutation in the SOX10 gene was considered to be the cause of Waardenburg
      syndrome in the proband. The clinical and genetic characterization of this family
      would help elucidate the genetic heterogeneity of SOX10 in Waardenburg syndrome
      type II. Moreover, the de novo pattern expanded the mutation data of SOX10.

PMID- 24735605
TI  - Effect of topical dexamethasone in reducing dysfunction after facial nerve crush
      injury in the rat.
AB  - OBJECTIVE: To date, the effect of topical steroid after a crush injury to rat
      facial nerve has rarely been reported on. The aim of this study was to
      investigate the effects of topical dexamethasone on recovery after a crush injury
      to the rat facial nerve, by functional, electrophysiological, and morphological
      evaluation. MATERIALS AND METHODS: We investigated the effects of topical
      dexamethasone on recovery after a crush injury to rat facial nerve by functional,
      electrophysiological and morphological evaluation. RESULTS: The functional
      recovery using vibrissae movement was significantly high scores in the
      experimental group than control group at two and three weeks post-crush. The
      recovery of the threshold of muscle action potential was significantly lowered in
      the experimental group compared to the control (p<0.05). However, there was no
      statistical significance in the nerve conduction velocity. The dexamethasone
      treatment groups showed a larger axon diameter and thicker myelin sheath than the
      control group. CONCLUSION: From our results, topical dexamethasone accelerates
      recovery of the crush-injured facial nerve.

PMID- 24735606
TI  - Laryngeal cleft: evaluation and management.
AB  - OBJECTIVES: Review the latest diagnostic and treatment modalities for laryngeal
      and laryngotracheoesophageal clefts as they can be a major cause of respiratory
      and feeding morbidity in the infant and pediatric population. METHODS: Literature
      review of published reports. RESULTS: The presentation of laryngeal cleft usually
      involves respiratory symptoms, such as stridor, chronic cough, aspiration, and
      recurrent respiratory infections. Clefts of the larynx and trachea/esophagus can
      occur in isolation, as part of a syndrome (Opitz-Frias, VATER/VACTERL, Pallister
      Hall, CHARGE), or with other associated malformations (gastrointestinal,
      genitourinary, cardiac, craniofacial). This publication reviews the presenting
      signs/symptoms, diagnostic options, prognosis, and treatment considerations based
      on over a decade of experience of the senior author with laryngeal clefts.
      CONCLUSIONS: Type I laryngeal clefts can be managed medically or surgically
      depending on the degree of morbidity. Types II, III, and IV require endoscopic or
      open surgery to avoid chronic respiratory and feeding complications.

PMID- 24735607
TI  - Long-term follow-up of otitis media with effusion in children: comparisons
      between a ventilation tube group and a non-ventilation tube group.
AB  - OBJECTIVE: The objective of this study was to investigate the long-term outcomes
      in children with otitis media with effusion who received either medical treatment
      or ventilation tubes. METHODS: We retrospectively analyzed the medical records of
      89 bilateral cases of otitis media with effusion in children who were recommended
      to receive ventilation tube insertion and were followed up for more than 5 years.
      Tympanic membrane was inspected by otoscopic examination. Hearing was evaluated
      with pure tone audiometry. The mean duration of follow-up was 8.4 years (range,
      5.2-15.7 years). Twenty-three children were treated without surgery, while 22
      were treated once by ventilation tube insertion and 44 were treated more than
      once by ventilation tube insertion. RESULTS: At the fifth year of follow-up, both
      groups of children who underwent ventilation tube insertion had more frequent
      tympanic membrane abnormalities than the medication group (8.7% in those treated
      without surgery, 72.7% in those treated once by ventilation tube insertion, and
      88.6% in those treated more than once by ventilation tube insertion). Common
      tympanic membrane abnormalities were retraction (27.0%) and tympanosclerotic
      plaque (23.6%), regardless of the treatment modality. At the fifth year follow
      up, the average air-conduction threshold was 10.0 dB (+/- 6.5 dB) in patients
      treated without surgery, 15.9 dB (+/- 11.2dB) in patients treated once by
      ventilation tube insertion, and 17.8 dB (+/- 7.6 dB) in those treated more than
      once by ventilation tube insertion. The audiological difference was significant
      when we compared the hearing level of children treated by medication without
      surgery to the two ventilation tube groups. CONCLUSION: Though ventilation tube
      insertion can resolve hearing loss quickly, there were more tympanic membrane
      abnormalities and a decline in hearing levels in our ventilation tube insertion
      group vs. the observation group measured 5 years later. Physicians should
      therefore be cautious when applying a ventilation tube in patients with otitis
      media with effusion and should explain the risks to patients who are a candidate
      for repeated ventilation tube insertion.

PMID- 24735608
TI  - Pediatric otogenic sigmoid sinus thrombosis: 12-Year experience.
AB  - OBJECTIVES: Otogenic sigmoid sinus thrombosis is a rare complication of acute
      otitis media. Treatment remains controversial particularly regarding extent of
      surgical intervention. The aim of the study was to review the 12-year experience
      of a major medical center with the treatment of sigmoid sinus thrombosis in
      children. METHODS: Retrospective case series identified by database review in a
      tertiary university-affiliated pediatric medical center. Twenty-four children
      aged 7-155 months were treated for sigmoid sinus thrombosis from 2000 through
      2011. RESULTS: The transverse sinus was also involved in 10 patients, and the
      jugular vein, in 4. Acute otitis media with mastoiditis was the causative factor
      in all cases. Subperiosteal abscess was diagnosed in 21 patients, 11 with
      epidural involvement. Treatment in all cases consisted of broad-spectrum
      antibiotics and ventilation tube insertion. Twenty-one children (87.5%) underwent
      mastoidectomy with removal of bone covering the sigmoid sinus to drain pus and
      remove granulations from the epidural cavity, without aspiration or sinus
      drainage. Twenty-two patients received low-molecular-weight heparin for 3-6
      months postoperatively. Children infected with Fusobacterium necrophorum had a
      longer and more severe course with coexisting osteomyelitis. There were no
      neurologic sequelae or hematologic complications. Follow-up imaging, performed in
      15 children, revealed partial or full recanalization in 87%. CONCLUSIONS:
      Relatively conservative surgical intervention appears to yield good results in
      children with sigmoid sinus thrombosis consequent to acute otitis media.
      Anticoagulants are safe if correctly administered and may prevent extension of
      the thrombus.

PMID- 24735609
TI  - Go6976, a FLT3 kinase inhibitor, exerts potent cytotoxic activity against acute
      leukemia via inhibition of survivin and MCL-1.
AB  - Mutations of the FMS-like tyrosine kinase 3 (FLT3) have been reported in about a
      third of patients with acute myeloid leukemia (AML). The presence of FLT3
      mutations confers a poor prognosis. Thus, pharmacological inhibitors of FLT3 are
      of therapeutic interest for AML. Go6976 is an indolocarbazole with a similar
      structural backbone to staurosporine. In the present study, we demonstrated that
      Go6976 displays a potent inhibitory activity against recombinant FLT3 using an in
      vitro kinase assay, with an IC50 value of 0.7nM. Go6976 markedly inhibited the
      proliferation of human leukemia cells having FLT3-ITD such as MV4-11 and MOLM13.
      We also observed that Go6976 showed minimal toxicity for human normal CD34(+)
      cells. Go6976 suppressed the phosphorylation of FLT3 and downstream signaling
      molecules such as STAT3/5, Erk1/2, and Akt in MV4-11 and MOLM13 cells.
      Interestingly, induction of apoptosis by Go6976 was associated with rapid and
      pronounced down-regulation of the anti-apoptotic protein survivin and MCL-1.
      Suppression of survivin protein expression by Go6976 was due to the inhibition of
      transcription via the suppression of STAT3/5. On the other hand, Go6976 induced
      proteasome-mediated degradation of MCL-1. Previously described FLT3 inhibitors
      such as PKC412 are bound by the human plasma protein, alpha1-acid glycoprotein,
      resulting in diminished inhibitory activity against FLT3. In contrast, we found
      that Go6976 potently inhibited phosphorylation of FLT3 and exerted cytotoxicity
      in the presence of human serum. In conclusion, Go6976 is a potent FLT3 inhibitor
      that displays a significant antiproliferative activity against leukemia cells
      with FLT3-ITD through the profound down-regulation of survivin and MCL-1. 

PMID- 24735610
TI  - The rigid steroid 21-hydroxy-6,19-epoxyprogesterone (21OH-6,19OP) is a
      dissociated glucocorticoid receptor modulator potentially useful as a novel
      coadjuvant in breast cancer chemotherapy.
AB  - Glucocorticoids (GCs) are steroid hormones widely used as coadjuvants in the
      treatment of solid tumors due to their anti-inflammatory effects. However,
      evidence show that they also may induce chemotherapy resistance, probably through
      their capacity to inhibit apoptosis triggered by antineoplastic drugs. GCs exert
      their action by regulating gene expression throughout two main mechanisms:
      transactivation, where the activated glucocorticoid receptor (GR) directly binds
      to certain genes; and transrepression, an indirect mechanism by which GR
      regulates other transcription factors activities. Recently, our group has shown
      that the rigid steroid 21-hydroxy-6,19-epoxyprogesterone (21OH-6,19OP) is a
      selective GR ligand that behaves as an agonist in transrepression assays and as
      an antagonist in transactivation ones. Here, we have evaluated the anti
      inflammatory activity of 21OH-6,19OP, its capacity to generate chemoresistance,
      as well as its mechanism of action. We found that 21OH-6,19OP inhibits nitrites
      formation and the inducible nitric oxide synthase (Nos-2) expression in
      macrophages. It also blocks the expression of both cyclooxygenase-2 (COX-2) and
      interleukin-8 (IL-8) triggered by tumor necrosis factor-alpha (TNF-alpha) in
      epithelial lung cancer cells. However, contrary to dexamethasone (DEX), 21OH
      6,19OP neither reverts the paclitaxel-induced caspase-3 activity, nor induces the
      anti-apoptotic Bcl-X(L) gene expression in murine tumor mammary epithelial cells;
      and importantly, it lacks GCs-associated chemoresistance in a mouse mammary tumor
      model. Together, our findings suggest that 21OH-6,19OP behaves as a dissociated
      GC that keeps anti-inflammatory action without affecting the apoptotic process
      triggered by chemotherapeutic drugs. For these reasons, this steroid may become a
      putative novel coadjuvant in the treatment of breast cancer.

PMID- 24735612
TI  - RNA-binding protein-mediated post-transcriptional controls of gene expression:
      integration of molecular mechanisms at the 3' end of mRNAs?
AB  - Initially identified as an occasional and peculiar mode of gene regulation in
      eukaryotes, RNA-binding protein-mediated post-transcriptional control of gene
      expression has emerged, over the last two decades, as a major contributor in the
      control of gene expression. A large variety of RNA-binding proteins (RBPs) allows
      the recognition of very diverse messenger RNA sequences and participates in the
      regulation of basically all cellular processes. Nevertheless, the rapid outcome
      of post-transcriptional regulations on the level of gene expression has favored
      the expansion of this type of regulation in cellular processes prone to rapid and
      frequent modulations such as the control of the inflammatory response. At the
      molecular level, the 3'untranslated region (3'UTR) of mRNA is a favored site of
      RBP recruitment. RBPs binding to these regions control gene expression through
      two major modes of regulation, namely mRNA decay and modulation of translational
      activity. Recent progresses suggest that these two mechanisms are often
      interdependent and might result one from the other. Therefore, different RBPs
      binding distinct RNA subsets could share similar modes of action at the molecular
      level. RBPs are frequent targets of post-translational modifications, thereby
      disclosing numerous possibilities for pharmacological interventions. However,
      redundancies of the transduction pathways controlling these modifications have
      limited the perspectives to define RBPs as new therapeutic targets. Through the
      analysis of several examples of RBPs binding to 3'untranslated region of mRNA, we
      present here recent progress and perspectives regarding this rapidly evolving
      field of molecular biology.

PMID- 24735611
TI  - Brazilin selectively disrupts proximal IL-1 receptor signaling complex formation
      by targeting an IKK-upstream signaling components.
AB  - The ligation of interleukin-1 receptor (IL-1R) or tumor necrosis factor receptor
      1 (TNFR1) induces the recruitment of adaptor proteins and their concomitant
      ubiquitination to the proximal receptor signaling complex, respectively. Such are
      upstream signaling events of IKK that play essential roles in NF-kappaB
      activation. Thus, the discovery of a substance that would modulate the
      recruitment of key proximal signaling elements at the upstream level of IKK has
      been impending in this field of study. Here, we propose that brazilin, an active
      compound of Caesalpinia sappan L. (Leguminosae), is a potent NF-kappaB inhibitor
      that selectively disrupts the formation of the upstream IL-1R signaling complex.
      Analysis of upstream signaling events revealed that brazilin markedly abolished
      the IL-1beta-induced polyubiquitination of IRAK1 and its interaction with IKK
      gamma counterpart. Notably, pretreatment of brazilin drastically interfered the
      recruitment of the receptor-proximal signaling components including IRAK1/4 and
      TRAF6 onto MyD88 in IL-1R-triggerd NF-kappaB activation. Interestingly, brazilin
      did not affect the TNF-induced RIP1 ubiquitination and the recruitment of RIP1
      and TRAF2 to TNFR1, suggesting that brazilin is effective in selectively
      suppressing the proximal signaling complex formation of IL-1R, but not that of
      TNFR1. Moreover, our findings suggest that such a disruption of IL-1R-proximal
      complex formation by brazilin is not mediated by affecting the heterodimerization
      of IL-1R and IL-1RAcP. Taken together, the results suggest that the anti-IKK
      activity of brazilin is induced by targeting IKK upstream signaling components
      and subsequently disrupting proximal IL-1 receptor signaling complex formation. 

PMID- 24735613
TI  - Current race in the development of DAAs (direct-acting antivirals) against HCV.
AB  - The direct-acting antivirals (DAAs) currently in development for treatment of
      hepatitis C fall into four categories: (i) NS3/4A protease inhibitors: ABT-450/r,
      faldaprevir, asunaprevir, GS-9256, vedroprevir (GS-9451), danoprevir, MK-5172,
      vaniprevir, sovaprevir, ACH-2684, narlaprevir and simeprevir, in addition to
      those that are already developed [telaprevir (Incivek(r)) and boceprevir
      (Victrelis(r))], (ii) NS5A protein inhibitors: ABT-267, daclatasvir, ledipasvir,
      ACH-2928, ACH-3102, PPI-668, AZD-7295, MK-8742, and GSK 2336805; (iii) NS5B
      (nucleoside-type) polymerase inhibitors: sofosbuvir (now approved by the FDA
      since 6 December 2013), GS-0938, mericitabine, VX-135, ALS 2158 and TMC 649128;
      (iv) NS5B (non-nucleoside-type) polymerase inhibitors: VX-222, ABT-072, ABT-333,
      deleobuvir, tegobuvir, setrobuvir, VCH-916, VCH-759, BMS-791325 and TMC-647055.
      Future drug combinations will likely exist of two or more DAAs belonging to any
      of the 4 categories, with the aim to achieve (i) pan-genotypic hepatitis C virus
      (HCV) activity, (ii) little or no risk for resistance; (iii) short duration (i.e.
      12 weeks) of treatment, and (iv) a sustained viral response (SVR) and definite
      cure of the disease. 

PMID- 24735614
TI  - The risk of HCV RNA contamination in serology screening instruments with a fixed
      needle for sample transfer.
AB  - BACKGROUND: Hepatitis C diagnostics involve antibody screening and confirmation
      of current infection by detection of HCV RNA positivity. In screening instruments
      with fixed pipetting needle, there is a risk of sample carry-over contamination.
      OBJECTIVES: The aim of this study was to evaluate the risk of such contamination
      in a proposed clinical setting. STUDY DESIGN: In the present study, known HCV RNA
      positive (n=149) and negative (n=149) samples were analysed by anti-HCV Abbott in
      an Architect instrument in an alternating fashion in order to test for
      contamination. RESULTS: In subsequent retesting of the previously HCV RNA
      negative samples, six samples (4%) were positive by the Cobas Taqman assay with a
      maximum level of 33 IU/mL. The results show that there is a risk for transfer of
      HCV in the Architect instrument but they also show that the levels of HCV RNA
      observed are low. CONCLUSIONS: We conclude that complementary HCV RNA testing on
      samples identified as anti-HCV positive by screening can be recommended because
      the complementary results are reliable in the majority of cases when either HCV
      RNA is negative or HCV RNA is positive with a level >1000 IU/mL. In a minority of
      cases, with low HCV RNA after anti-HCV antibody screening, cross-contamination
      should be suspected and a new sample requested for HCV RNA testing. This strategy
      would reduce the need for obtaining a new sample from the vast majority of
      patients with a newly discovered HCV antibody positivity.

PMID- 24735616
TI  - Occupational rehabilitation programs for musculoskeletal pain and common mental
      health disorders: study protocol of a randomized controlled trial.
AB  - BACKGROUND: Long-term sick leave has considerably negative impact on the
      individual and society. Hence, the need to identify effective occupational
      rehabilitation programs is pressing. In Norway, group based occupational
      rehabilitation programs merging patients with different diagnoses have existed
      for many years, but no rigorous evaluation has been performed. The described
      randomized controlled trial aims primarily to compare two structured
      multicomponent inpatient rehabilitation programs, differing in length and
      content, with a comparative cognitive intervention. Secondarily the two inpatient
      programs will be compared with each other, and with a usual care reference group.
      METHODS/DESIGN: The study is designed as a randomized controlled trial with
      parallel groups. The Social Security Office performs monthly extractions of sick
      listed individuals aged 18-60 years, on sick leave 2-12 months, with sick leave
      status 50% - 100% due to musculoskeletal, mental or unspecific disorders. Sick
      listed persons are randomized twice: 1) to receive one of two invitations to
      participate in the study or not receive an invitation, where the latter
      "untouched" control group will be monitored for future sick leave in the National
      Social Security Register, and 2) after inclusion, to a Long or Short inpatient
      multicomponent rehabilitation program (depending on which invitation was sent) or
      an outpatient cognitive behavioral therapy group comparative program. The Long
      program consists of 3 1/2 weeks with full rehabilitation days. The Short program
      consists of 4 + 4 full days, separated by two weeks, in which a workplace visit
      will be performed if desirable. Three areas of rehabilitation are targeted:
      mental training, physical training and work-related problem solving. The primary
      outcome is number of sick leave days. Secondary outcomes include time until full
      sustainable return to work, health related quality of life, health related
      behavior, functional status, somatic and mental health, and perceptions of work.
      In addition, health economic evaluation will be performed, and the implementation
      of the interventions, expectations and experiences of users and service providers
      will be investigated with different qualitative methods. TRIAL REGISTRATION:
      ClinicalTrials.gov: NCT01926574.

PMID- 24735617
TI  - Editorial: International Cow Fertility Conference 'New Science - New Practices'
      in Westport, Ireland, in 2014.

PMID- 24735615
TI  - Identification of miR-26 as a key mediator of estrogen stimulated cell
      proliferation by targeting CHD1, GREB1 and KPNA2.
AB  - INTRODUCTION: Estrogen signaling is pivotal in the progression of estrogen
      receptor positive breast cancer primarily by the regulation of cell survival and
      proliferation. Micro (mi)RNAs have been demonstrated to be regulated by estrogen
      to mediate estrogenic effects. Herein, we determined the role of estrogen
      regulated miR-26 and its underlying molecular mechanisms associated with estrogen
      receptor (ER)+ breast cancer proliferation. METHODS: The expression of miR-26a
      and miR-26b was evaluated by real-time quantitative (RT)-PCR. The expression of
      miR-26a or miR-26b was modulated in ER+ breast cancer cells (MCF-7 and T47D) and
      tumor cell growth in vitro and an in vivo xenograft model was determined.
      Bioinformatics analyses were utilized to screen for estrogen responsive genes,
      which were also predicted to be targeted by miR-26. Luciferase reporter assays
      were performed to confirm miR-26 regulation of the 3' UTR of target genes. The
      levels of miR-26 target genes (CHD1, GREB1 and KPNA2) were evaluated by western
      blotting and immunohistochemistry. RESULTS: Estrogen reduced the expression of
      miR-26a and miR-26b in ER+ breast cancer cells. Forced expression of miR-26a or
      miR-26b significantly inhibited the estrogen stimulated growth of ER+ breast
      cancer cells and tumor growth in xenograft models, whereas miR-26a/b depletion
      increased the growth of ER+ breast cancer cells in the absence of estrogen
      treatment. Screening of estrogen responsive genes, which were also predicted to
      be targeted by miR-26, identified GREB1 and nine other genes (AGPAT5, AMMECR1,
      CHD1, ERLIN1, HSPA8, KPNA2, MREG, NARG1, and PLOD2). Further verification has
      identified nine genes (AGPAT5, CHD1, ERLIN1, GREB1, HSPA8, KPNA2, MREG, NARG1 and
      PLOD2) which were directly targeted by miR-26 via their 3' UTR. Functional
      screening suggested only three estrogen regulated miR-26 target genes (CHD1,
      GREB1 and KPNA2) were involved in the regulation of estrogen promoted cell
      proliferation. Depletion of either CHD1, GREB1 or KPNA2 significantly abrogated
      the enhanced growth of ER+ breast cancer cells due to miR-26 depletion. We
      further demonstrated that estrogen stimulated c-MYC expression was both
      sufficient and necessary for the diminished expression of miR-26a and miR-26b.
      CONCLUSIONS: We have identified a novel estrogen/MYC/miR-26 axis that mediates
      estrogen stimulated cell growth via CHD1, GREB1 and KPNA2.

PMID- 24735619
TI  - [Optimize the prevention and management of heart failure according to the new
      guideline].

PMID- 24735620
TI  - [New view on the pathogenesis of ischemic heart disease].

PMID- 24735618
TI  - TCMSP: a database of systems pharmacology for drug discovery from herbal
      medicines.
AB  - BACKGROUND: Modern medicine often clashes with traditional medicine such as
      Chinese herbal medicine because of the little understanding of the underlying
      mechanisms of action of the herbs. In an effort to promote integration of both
      sides and to accelerate the drug discovery from herbal medicines, an efficient
      systems pharmacology platform that represents ideal information convergence of
      pharmacochemistry, ADME properties, drug-likeness, drug targets, associated
      diseases and interaction networks, are urgently needed. DESCRIPTION: The
      traditional Chinese medicine systems pharmacology database and analysis platform
      (TCMSP) was built based on the framework of systems pharmacology for herbal
      medicines. It consists of all the 499 Chinese herbs registered in the Chinese
      pharmacopoeia with 29,384 ingredients, 3,311 targets and 837 associated diseases.
      Twelve important ADME-related properties like human oral bioavailability, half
      life, drug-likeness, Caco-2 permeability, blood-brain barrier and Lipinski's rule
      of five are provided for drug screening and evaluation. TCMSP also provides drug
      targets and diseases of each active compound, which can automatically establish
      the compound-target and target-disease networks that let users view and analyze
      the drug action mechanisms. It is designed to fuel the development of herbal
      medicines and to promote integration of modern medicine and traditional medicine
      for drug discovery and development. CONCLUSIONS: The particular strengths of
      TCMSP are the composition of the large number of herbal entries, and the ability
      to identify drug-target networks and drug-disease networks, which will help
      revealing the mechanisms of action of Chinese herbs, uncovering the nature of TCM
      theory and developing new herb-oriented drugs. TCMSP is freely available at
      http://sm.nwsuaf.edu.cn/lsp/tcmsp.php.

PMID- 24735621
TI  - [Chinese guidelines for the diagnosis and treatment of heart failure 2014].

PMID- 24735622
TI  - [New thought from American new guideline on the treatment of blood cholesterol].

PMID- 24735623
TI  - [Impact of exogenous fibroblast growth factor 21 on atherosclerosis in
      apolipoprotein E deficient mice].
AB  - OBJECTIVE: To explore the effects and related mechanisms of exogenous fibroblast
      growth factor (FGF) 21 on atherosclerosis in apolipoprotein E deficient (apoE-/-)
      mice. METHODS: Male 17-week-old C57BL/6J mice and apoE-/- mice were randomly
      divided into three groups (n = 12 each): blank control group (C vehicle),
      atherosclerosis group without FGF21 (apoE-/- vehicle) and apoE-/- plus FGF21 (100
      ug * kg-1 * d-1 subcutaneously treatment) . All mice were fed with high-fat diet
      for 4 weeks. After 4 weeks treatments, atherosclerotic lesions in aortic arch and
      inner diameter of abdominal aorta were measured by ultrasonography. Plasma lipid
      profiles, CRP and TNFalpha were measured. The whole aorta and aortic root were
      prepared for HE and oil red O staining to analyze lesion areas. RESULTS: There
      was no evident plaque in C vehicle group. TC/HDL-C, LDL-C/HDL-C, non-HDL-C,
      expression of CRP and TNFalpha were significantly higher in apoE-/- vehicle group
      than in C vehicle group (all P < 0.05). IMT of aorta [(156.4 +/- 17.6)um vs.
      (57.8 +/- 7.4)um] were significantly higher in apoE-/- vehicle group than in C
      vehicle group (all P < 0.05). While FGF21 significantly reduced the lesion area
      in aorta arch [(1.42 +/- 0.16) mm2 vs. (2.30 +/- 0.10) mm2, P < 0.05] and the
      inner diameter of abdominal aorta [(0.97 +/- 0.03) mm vs. (0.75 +/- 0.18) mm, P <
      0.05] compared to apoE-/- vehicle group. Similarly, TC/HDL-C(5.11 +/- 0.70), LDL
      C/HDL-C(3.90 +/- 0.76), non-HDL-C[(6.33 +/- 1.22)mmol/L], plasma CRP[(4.20 +/-
      1.03)mmol/L] and plasma TNFalpha[(1.29 +/- 0.47)mmol/L] were also reduced by
      FGF21( all P < 0.05 vs. apoE-/- vehicle). Moreover, FGF21 decreased the
      IMT[(107.2 +/- 33.5)um vs. (156.4 +/- 17.6)um], lesion area of aorta [(14.26 +/-
      3.5)%] vs. [(23.06 +/- 4.16)%] and plaque size of aorta root [(21.75 +/- 7.14)%
      vs. (38.03 +/- 5.76)%] (all P < 0.05 vs. apoE-/- vehicle). CONCLUSIONS: FGF21 can
      protect apoE-/- mice from atherosclerosis by modifying lipid profiles and
      downregulating CRP and TNFalpha expressions.

PMID- 24735624
TI  - [Anti-inflammatory effects of apoprotein AI are mediated via modulating
      macrophage polarity].
AB  - OBJECTIVE: To explore the anti-inflammatory mechanisms of high density
      lipoprotein (HDL) by observing the effects of apoprotein (apo)AI, a major protein
      component of HDL, on the inflammatory macrophage cell polarity. METHODS: Cultured
      mice marrow-derived macrophages were stimulated with lipopolysaccharide and
      interferon after 10 ug/ml of apoAI were added to the macrophages for 24 hours.
      The expression of membrane molecules CD16/32, CD206 were detected by fluorescence
      activated cell sorting (FACS). ELISA was used to detect the secretion of IL-10
      and IL-12. Real-time quantitative PCR was used to detect the mRNA expression of
      TLR4, MyD88 and IRF5. RESULTS: Compared to macrophages stimulated by interferon
      and lipopolysaccharide but without pretreatment with apoAI, pre-incubation with
      apoAI significantly downregulated the expression of CD16/32 (91.17% +/- 1.99%
      vs.50.47% +/- 1.02%, P < 0.05), IL-12 [(747.27 +/- 3.74)pg/ml vs. (73.80 +/-
      4.56)pg/ml, P < 0.05], upregulated the expression of CD206(0.33% +/- 0.12% vs.
      3.00% +/- 0.36%, P < 0.05), IL -10 expression [(23.56 +/- 4.30) pg/ml vs.(32.91
      +/- 2.47) pg/ml, P < 0.05], and reduced the mRNA expression of TLR4 (1.000 +/-
      0.025 vs.0.708 +/- 0.003, P < 0.05) , MyD88 (1.591 +/- 0.005 vs. 1.341 +/- 0.005,
      P < 0.05) , IRF5 (0.954 +/- 0.005 vs. 0.463 +/- 0.003, P < 0.05) . CONCLUSION:
      ApoAI enhances the switch of inflammatory macrophages to anti-inflammatory
      macrophages possibly through inhibiting TLR4-MyD88-IRF5 pathway.

PMID- 24735625
TI  - [Plasma scavenger receptor BI and CD36 expression change and susceptibility of
      atherosclerosis in patients post liver transplantation].
AB  - OBJECTIVE: To explore the association between expression changes of plasma
      macrophages scavenger receptor (SR)-BI and CD36 and risk of arteriosclerosis in
      end-stage liver disease (ESLD) patients post liver transplantation. METHODS: A
      total of 20 liver transplantation patients were included. Clinical data including
      blood pressure, blood lipid, blood glucose, incidence of new-onset cardiovascular
      events were obtained. Plasma macrophages scavenger receptor SR-BIand CD36
      expressions were detected by polymerase chain reaction (RT-PCR) and Western-blot
      before and at 1 year after liver transplantation. RESULTS: The serum levels of TC
      [(5.34 +/- 0.87) mmol/L vs. (4.27 +/- 0.91) mmol/L], TG [(2.47 +/- 0.81) mmol/L
      vs. (1.02 +/- 0.49) mmol/L] and LDL-C [(3.36 +/- 0.67) mmol/L vs. (2.14 +/- 0.74)
      mmol/L] were significantly increased (P < 0.05) while the serum level of HDL-C
      [(0.98 +/- 0.84) mmol/L vs. (1.58 +/- 0.34) mmol/L] was significantly reduced (P
      < 0.05) at 1 year post transplantation compared to before-transplantation levels.
      One patient developed non-ST segment elevation myocardial infarction and treated
      with percutaneous coronary intervention, another patient developed atrial
      fibrillation at one year after transplantation. The plasma mRNA expression of SR
      BI was reduced (20.44 +/- 0.60 vs. 23.12 +/- 0.69, P < 0.05) while the expression
      of CD36 mRNA was upregulated (20.91 +/- 0.35 vs. 18.55 +/- 0.62, P < 0.05) at 1
      year after liver transplantation compare with that of before the transplantation.
      Similarly, the plasma protein expression of SR-BIwas reduced (0.21 +/- 0.13 vs.
      0.64 +/- 0.28, P < 0.05) while the protein expression of CD36 was upregulated
      (0.94 +/- 0.13 vs. 0.42 +/- 0.19, P < 0.05) at 1 year after liver transplantation
      compare with that of before the transplantation. CONCLUSION: Plasma expression
      changes of SR-BI and CD36 might contribute to the dyslipidemia and contribute to
      the atherosclerosis susceptibility after liver transplantation.

PMID- 24735626
TI  - [Clinical characteristics of infective endocarditis: analysis of 368 cases].
AB  - OBJECTIVE: This retrospective study is performed to analyze the epidemiological
      and clinical features of patients with infective endocarditis (IE) hospitalized
      in Fuwai Cardiovascular Hospital during the latest 7 years. METHODS: This
      retrospective study included a cohort of 368 infective endocarditis patients
      hospitalized in Fuwai Hospital form August 2005 to August 2012. Predisposing
      cardiac diseases, causative organisms, clinical features and outcomes were
      analyzed. Risk factors related to outcome including NYHA classes, causative
      organisms and complications, were evaluated. RESULTS: Among the IE patients, 6.8%
      (25/368) patients had rheumatic heart diseases 31.8% (117/368) had congenital
      heart diseases, 22.8% (84/368) were post-PCI or operative endocarditis and IE
      developed in 14.1% (52/368) patients without previous cardiac diseases. Blood
      culture positive rate was 46.2% (170/368). Streptococci viridians [27.6% (47/170)
      ]were the most common causative organisms, followed by coagulase-negative
      staphylococci [15.9% (27/170) ]. Fever and cardiac murmur were the most common
      clinical presentations. Congestive heart failure was the most common complication
      [87.8% (323/368)]. Systemic and pulmonary embolism occurred in 16.0% patients,
      80.9% IE was detected by echocardiography. In-hospital mortality rate was 6.7%,
      mostly due to refractory congestive heart failure and sepsis. Subgroup analysis
      showed that incidence of post-PCI or operative endocarditis was significantly
      higher in IE patients hospitalized after 2009 compared to IE patients
      hospitalized before 2009 (27.5% vs. 19.2%, P < 0.05) . Higher incidence of
      staphylococcal infection was evidenced in mechanical valves than in native valves
      (44.4% vs. 19.8%, P < 0.05). CONCLUSION: During the past decade, there is a
      significant change on epidemiology and clinical features of IE in China.
      Incidence of post-surgical and interventional IE increased significantly.
      Staphylococcal and Gram negative bacilli infection are major pathorganisms of
      endocarditis of mechanical valves. Due to the lower positive rate of blood
      culture, echocardiography serves as the most important diagnostic tool for
      infective endocarditis.

PMID- 24735627
TI  - [Midterm outcome of surgical therapy for congenitally corrected transposition of
      the great arteries with morphologically involuted left ventricle].
AB  - OBJECTIVE: We followed up all the patients underwent pulmonary artery banding
      (PAB) with or without the second stage double switch (DS) operation to compare
      the midterm outcomes between the DS and the prolonged palliative PAB. METHODS:
      From January 2005 to June 2012, 40 consecutive patients diagnosed with congenital
      corrected transposition of the great arteries (cc-TGA) with morphologically
      involuted left ventricle were included in this retrospective cohort study. Every
      patient underwent the first stage PAB. The second stage DS was performed in 15
      patients (DS group) and the palliative PAB was prolonged in the other 25 patients
      (PAB group). The median age at PAB was 3.1 years (range, 3 months to 8 years),
      weight was 11.5 kg (range, 5.0 kg to 21.5 kg). The patients were followed up
      after surgery. RESULTS: Follow-up time was (3.4 +/- 0.7) years. Overall mortality
      was 33.3% (5/15) in DS group and 4.0% (1/25) in PAB group (P < 0.05). The ratio
      of NYHAI-II was 80.0% (8/10) in DS group and 95.9% (23/24) in PAB group (P <
      0.05) and the mean left ventricle ejection fraction was (51.4 +/- 9.6)% in DS
      group and (61.0 +/- 6.4)% in PAB group(P < 0.01) during follow up. There was no
      PAB related cyanosis or ventricular dysfunction and the trans-banding pressure
      gradient was (46.9 +/- 21.5)mmHg (1 mmHg = 0.133 kPa) in PAB group.
      Echocardiography examination revealed moderate to large aortic regurgitation in 3
      patients and severe post-double switch operative arrhythmias was found in 2
      patients in DS group. The age at PAB (HR = 13.30, 95%CI:6.28-14.02, P < 0.05) and
      left ventricle dysfunction (HR = 4.77, 95%CI:2.71-8.68, P < 0.05) were identified
      as the risk factors for mortality after DS. CONCLUSION: Compared to the DS, the
      prolonged palliative PAB procedure is associated with lower mortality and better
      cardiac function post operation.

PMID- 24735628
TI  - [Protective effects of soybean isoflavone on human umbilical vein endothelial
      cell injury induced by H2O2 and lipopolysaccharide].
AB  - OBJECTIVE: To investigate the protective effects and related mechanisms of
      soybean isoflavone (SI) on human umbilical vein endothelial cells (HUVECs) injury
      induced by H2O2 and lipopolysaccharide (LPS). METHODS: H2O2 and LPS were used to
      induce HUVECs injury in vitro. Nine experimental groups were examined: control
      group, H2O2 (2 mmol/L for 4 h), LPS (2 mmol/L for 4 h), H2O2+low dose SI (1
      mg/ml), H2O2+moderate dose SI (2.5 mg/ml), H2O2+high dose SI (5 mg/ml), LPS+low
      dose SI (1 mg/ml), LPS+moderate dose SI (2.5 mg/ml), LPS+high dose SI (5 mg/ml).
      The survival ratio of HUVECs was detected with MTT assay. The cultured cells were
      loaded by Fura-2/AM and the change of [Ca2+] in HUVECs was measured by
      fluorospectrophotometry. The contents of malondialdehyde (MDA), superoxide
      dismutase (SOD), reduced glutathione (GSH-Px) were measured by the commercial
      kits. The levels of tissue plasminogen activator IL-6 in the supematant were
      measured by enzyme linked immunosorbent assay (ELISA) kits. Apoptosis rate of the
      HUVECs was analyzed by flow cytometry. RESULTS: H2O2 and LPS significantly
      decreased HUVECs viability, increased the contents of MDA, IL-6 and decreased the
      contents of SOD and GSH-Px, and increased the apoptosis rate [(37.8 +/- 1.8)% and
      (38.9 +/- 1.1)%]. Co-treatment with SI could reduce MDA and IL-6 while increase
      SOD and GSH-Px and reduce apoptosis in a dose-dependent manner. CONCLUSION: The
      findings demonstrate that soybean isoflavone could attenuate H2O2 and LPS induced
      injury in human umbilical vein endothelial cells through protecting mitochondrial
      function, improving antioxygenic activity, and suppressing the mobilization of
      cytosolic calcium.

PMID- 24735629
TI  - [A cross-sectional study of factors related to traditional Chinese medicine use
      for hospitalized acute coronary syndrome patients in China's level 2 hospitals].
AB  - OBJECTIVE: To explore the current status on traditional Chinese medicine (TCM)
      use for hospitalized acute coronary syndrome patients in China's level 2
      hospitals, and to explore associated factors of TCM use for these patients.
      METHODS: This survey was performed in 102 level 2 hospitals from 15 provinces or
      autonomous region in China. Patients admitted to these hospitals with acute
      coronary syndrome during September 2011 to May 2012 were eligible for this study.
      Information on TCM use was obtained from their medical records. Chi-square test
      and logistic regression analysis were used to explore the related factors of TCM
      use in these patients. RESULTS: We recruited 5 432 acute coronary syndrome
      patients in this study, TCM was applied to 3 503 patients (64.5%). Multivariable
      logistic regression showed that pre-hospital TCM use was positively related with
      in-hospital TCM use (OR = 2.08, P < 0.01) , while pre-hospital use of 4 medicines
      recommended by the guidelines(including aspirin/clopidogrel, beta acceptor
      blocker, stain and angiotensin converting enzyme inhibitor/angiotensin converting
      enzyme receptor blocker ), being a smoker and diagnosis of myocardial infarction
      rather than unstable angina at hospital discharge were negatively related with in
      hospital TCM use (the ORs were 0.58, 0.78 and 0.71, respectively, all P < 0.01).
      The TCM use varied significantly between regions. Taking southwest region as a
      reference, the ORs varied between 2.98-13.37 (all P < 0.01) in eastern China,
      south China, central China, north China, northwest and northeast regions.
      CONCLUSIONS: TCM is widely used in hospitalized acute coronary syndrome patients
      in China's resource-constrained level 2 hospitals. Pre-hospital TCM use is
      positively correlated with in-hospital TCM use for these patients.

PMID- 24735630
TI  - [Efficacy of noninvasive ventilation on in-hospital mortality in patients with
      acute cardiogenic pulmonary edema: a meta-analysis].
AB  - OBJECTIVE: To evaluate the efficacy of noninvasive ventilation on in-hospital
      mortality in adult patients with acute cardiogenic pulmonary edema (ACPE) .
      METHODS: We searched PubMed, Embase, Wanfang, CNKI data to find relevant
      randomized controlled trials of noninvasive ventilation for ACPE, which were
      reported from January 1980 to December 2012. Meta-analysis was performed with
      software of RevMan 5.1. RESULTS: According to inclusive criteria and exclusion
      criteria, 35 randomized controlled trials with 3 204 patients were enrolled for
      analyses. Meta-analysis of the trials showed that continuous positive airway
      pressure (CPAP) reduced in-hospital mortality by 43% (RR = 0.57, 95%CI 0.43-0.75,
      P < 0.01) and bilevel positive pressure ventilation (BiPAP) reduced mortality by
      31% (RR = 0.69, 95%CI 0.51-0.94, P = 0.02) compared with standard therapy. There
      were no significant differences in in-hospital mortality between BiPAP and CPAP
      (RR = 1.09, 95%CI 0.80-1.49, P = 0.57) and myocardial infarction rate (BiPAP vs.
      CPAP: RR = 1.20, 95%CI 0.95-1.52, P = 0.12; BiPAP vs. standard therapy: RR =
      1.10, 95%CI 0.88-1.38, P = 0.40). CONCLUSION: Noninvasive ventilation (BiPAP and
      CPAP) could reduce in-hospital mortality of adult patients with ACPE, which could
      be used as first-line management strategies for these patients.

PMID- 24735631
TI  - [A case of Stanford type A aortic dissection combined with bone fascia syndrome].

PMID- 24735632
TI  - [Misdiagnosis as primary hypertension in 4 adult patients with secondary
      hypertension due to simple interrupted aortic arch].

PMID- 24735633
TI  - [Infective endocarditis caused by Enterococcus faecium: a case report].

PMID- 24735634
TI  - [A case report of infective endocarditis caused byabiotrophia and
      granulicatella].

PMID- 24735635
TI  - [Role of platelets in the pathogenesis of atherothrombosis].

PMID- 24735636
TI  - [Role and mechanism of canonical transient receptor potential channels in the
      pathogenesis of hypertension].

PMID- 24735637
TI  - Phosphorylated H2AX in parthenogenetically activated, in vitro fertilized and
      cloned bovine embryos.
AB  - In vitro embryo production methods induce DNA damage in the embryos. In response
      to these injuries, histone H2AX is phosphorylated (gammaH2AX) and forms foci at
      the sites of DNA breaks to recruit repair proteins. In this work, we quantified
      the DNA damage in bovine embryos undergoing parthenogenetic activation (PA), in
      vitro fertilization (IVF) or somatic cell nuclear transfer (SCNT) by measuring
      gammaH2AX accumulation at different developmental stages: 1-cell, 2-cell and
      blastocyst. At the 1-cell stage, IVF embryos exhibited a greater number of
      gammaH2AX foci (606.1 +/- 103.2) and greater area of gammaH2AX staining (12923.6
      +/- 3214.1) than did PA and SCNT embryos. No differences at the 2-cell stage were
      observed among embryo types. Although PA, IVF and SCNT were associated with
      different blastocyst formation rates (31.1%, 19.7% and 8.3%, P < 0.05), no
      differences in the number of gammaH2AX foci or area were detected among the
      treatments. gammaH2AX is detected in bovine preimplantation embryos produced by
      PA, IVF and SCNT; the amount of DNA damage was comparable among those embryos
      developing to the blastocyst stage among different methods for in vitro embryo
      production. While IVF resulted in increased damage at the 1-cell embryo stage, no
      difference was observed between PA and SCNT embryos at any developmental stage.
      The decrease in the number of double-stranded breaks at the blastocyst stage
      seems to indicate that DNA repair mechanisms are functional during embryo
      development. 

PMID- 24735638
TI  - South Korea's national health insurer sues tobacco industry for $51.9m in
      damages.

PMID- 24735639
TI  - FGF-2 released from degenerating neurons exerts microglial-induced
      neuroprotection via FGFR3-ERK signaling pathway.
AB  - BACKGROUND: The accumulation of activated microglia is a hallmark of various
      neurodegenerative diseases. Microglia may have both protective and toxic effects
      on neurons through the production of various soluble factors, such as chemokines.
      Indeed, various chemokines mediate the rapid and accurate migration of microglia
      to lesions. In the zebra fish, another well-known cellular migrating factor is
      fibroblast growth factor-2 (FGF-2). Although FGF-2 does exist in the mammalian
      central nervous system (CNS), it is unclear whether FGF-2 influences microglial
      function. METHODS: The extent of FGF-2 release was determined by ELISA, and the
      expression of its receptors was examined by immunocytochemistry. The effect of
      several drug treatments on a neuron and microglia co-culture system was estimated
      by immunocytochemistry, and the neuronal survival rate was quantified. Microglial
      phagocytosis was evaluated by immunocytochemistry and quantification, and
      microglial migration was estimated by fluorescence-activated cell sorting (FACS).
      Molecular biological analyses, such as Western blotting and promoter assay, were
      performed to clarify the FGF-2 downstream signaling pathway in microglia.
      RESULTS: Fibroblast growth factor-2 is secreted by neurons when damaged by
      glutamate or oligomeric amyloid beta 1-42. FGF-2 enhances microglial migration
      and phagocytosis of neuronal debris, and is neuroprotective against glutamate
      toxicity through FGFR3-extracellular signal-regulated kinase (ERK) signaling
      pathway, which is directly controlled by Wnt signaling in microglia. CONCLUSIONS:
      FGF-2 secreted from degenerating neurons may act as a 'help-me' signal toward
      microglia by inducing migration and phagocytosis of unwanted debris.

PMID- 24735640
TI  - Engineering theranostic nanovehicles capable of targeting cerebrovascular amyloid
      deposits.
AB  - Cerebral amyloid angiopathy (CAA) is characterized by the deposition of amyloid
      beta (Abeta) proteins within the walls of the cerebral vasculature with
      subsequent aggressive vascular inflammation leading to recurrent hemorrhagic
      strokes. The objective of the study was to develop theranostic nanovehicles
      (TNVs) capable of a) targeting cerebrovascular amyloid; b) providing magnetic
      resonance imaging (MRI) contrast for the early detection of CAA; and c) treating
      cerebrovascular inflammation resulting from CAA. The TNVs comprised of a
      polymeric nanocore made from Magnevist (MRI contrast agent) conjugated chitosan.
      The nanocore was also loaded with cyclophosphamide (CYC), an immunosuppressant
      shown to reduce the cerebrovascular inflammation in CAA. Putrescine modified
      F(ab')2 fragment of anti-amyloid antibody, IgG4.1 (pF(ab')24.1) was conjugated to
      the surface of the nanocore to target cerebrovascular amyloid. The average size
      of the control chitosan nanoparticles (conjugated with albumin and are devoid of
      Magnevist, CYC, and pF(ab')24.1) was 164+/-1.2 nm and that of the TNVs was 239+/
      4.1 nm. The zeta potential values of the CCNs and TNVs were 21.6+/-1.7 mV and
      11.9+/-0.5 mV, respectively. The leakage of Magnevist from the TNVs was a modest
      0.2% over 4 days, and the CYC release from the TNVs followed Higuchi's model that
      describes sustained drug release from polymeric matrices. The studies conducted
      in polarized human microvascular endothelial cell monolayers (hCMEC/D3) in vitro
      as well as in mice in vivo have demonstrated the ability of TNVs to target
      cerebrovascular amyloid. In addition, the TNVs provided contrast for imaging
      cerebrovascular amyloid using MRI and single photon emission computed tomography.
      Moreover, the TNVs were shown to reduce pro-inflammatory cytokine production by
      the Abeta challenged blood brain barrier (BBB) endothelium more effectively than
      the cyclophosphamide alone.

PMID- 24735641
TI  - Electrocardiographic findings of takotsubo cardiomyopathy as compared with those
      of anterior acute myocardial infarction.
AB  - Takotsubo cardiomyopathy (TC) is a recently recognized novel cardiac syndrome
      characterized by transient left ventricular dysfunction without obstructive
      coronary disease, electrocardiographic (ECG) changes (ST-segment elevation and/or
      negative T wave) or elevated cardiac enzymes. Because the clinical features and
      ECG findings of TC mimic those of anterior acute myocardial infarction (AMI) with
      occlusion of the left anterior descending coronary artery, differential diagnosis
      has an important role in selecting the most appropriate treatment strategy.
      Especially in the acute phase, differential diagnosis is essential for deciding
      whether reperfusion therapy is required. Although it has been suggested that ECG
      does not allow reliable differentiation between TC and anterior AMI, several ECG
      criteria distinguishing TC from anterior AMI have been proposed. In this review,
      we discuss ECG findings of TC, especially in the acute phase, compare them with
      those of anterior AMI, and identify ECG features that may facilitate early
      recognition of this disease. 

PMID- 24735642
TI  - Electromyographic assessment of isometric and dynamic activation characteristics
      of the latissimus dorsi muscle.
AB  - The aim of the current study was to analyze the activation characteristics and
      potential compartmentalization of the latissimus dorsi (LD) muscle during common
      maximal voluntary isometric contractions (MVICs) and functional dynamic tasks.
      Surface electromyography (sEMG) was used to measure activation magnitudes from
      four electrode sites (referenced to the T10, T12, L1 & L4 LD vertebral origins)
      across the fanning muscle belly of the LD. In addition, EMG waveforms were cross
      correlated to study temporal activation timing between electrode sites (T10-T12,
      T12-L1, L1-L4 & T10-L4). The MVICs that were tested included a humeral adduction,
      humeral adduction with internal rotation, a chest-supported row and a humeral
      extension. Dynamic movements included sagittal lift/lowers from the floor to
      knee, knee to hip and hip to shoulder. No magnitude-based (p=0.6116) or temporal
      based differences were observed between electrode sites during the MVIC trials.
      During dynamic movements no temporal-based, but some magnitude-based differences
      between electrode sites were observed to be present; these differences were small
      in magnitude and were observed for both the maximum (p=0.0002) and mean
      (p=0.0002) EMG magnitudes. No clear pattern of compartmentalization was uncovered
      in the contractions studied here. In addition to these findings, it was
      determined that the most effective MVIC technique for LD EMG normalization
      purposes was a chest-supported row MVIC, paired with a T12 electrode site. 

PMID- 24735643
TI  - Optimization of anti-virulence PqsR antagonists regarding aqueous solubility and
      biological properties resulting in new insights in structure-activity
      relationships.
AB  - Increasing antibiotic resistance urgently requires novel therapeutic options to
      combat bacterial infections. The anti-virulence therapy selectively intervening
      with pathogenicity without affecting bacterial viability is such a strategy to
      overcome resistance. We consider the virulence regulator PqsR as an attractive
      target in the human pathogen Pseudomonas aeruginosa, and recently discovered the
      first PqsR antagonists, which, however, suffered from poor aqueous solubility. In
      this work, the antagonists were structurally modified to become more soluble, and
      their structure-activity as well as structure-property relationships were
      studied. A novel promising compound with improved solubility and enhanced anti
      virulence activity was discovered (IC50: 3.8 MUM, pyocyanin). Our findings
      emphasize the crucial role of substituents at the 3-position and the carbonyl
      group at the 4-position for ligand-receptor interactions, and illuminate the way
      for further optimization of PqsR antagonists as anti-virulence agents. 

PMID- 24735645
TI  - Synthesis, crystal studies, anti-tuberculosis and cytotoxic studies of 1-[(2E)-3
      phenylprop-2-enoyl]-1H-benzimidazole derivatives.
AB  - Series of 1-[(2E)-3-phenylprop-2-enoyl]-1H-benzimidazole derivatives were
      synthesized and characterized by spectral methods. Among 21 derivatives, single
      crystals of 3a and 3l were grown and their structural parameters were evaluated.
      Newly synthesized compounds were screened for anti-tubercular activity and the
      MIC was determined against Mycobacterium tuberculosis H37Rv by Microplate Alamar
      Blue Assay (MABA) method. Majority of the compounds exhibited a promising
      inhibition of M. tuberculosis and the molecules functionalized with electron
      donating groups at C-2 carbon of benzimidazole moiety were found to be more
      active in inhibiting M. tuberculosis. Further, more promising compounds viz., 3b,
      3i and 3l were tested for their cytotoxic activity. Compound 3l was found to
      display excellent activity (IC50 < 10 MUg mL(-1)) with 100% cell lysis at 30 MUg
      mL(-1) concentration against A549 (Human lung carcinoma) and 8E5 (Human; Acute
      Lymphoblastic Leukemia) cell lines. 

PMID- 24735644
TI  - Imidazole-derived 2-[N-carbamoylmethyl-alkylamino]acetic acids, substrate
      dependent modulators of insulin-degrading enzyme in amyloid-beta hydrolysis.
AB  - Insulin degrading enzyme (IDE) is a highly conserved zinc metalloprotease that is
      involved in the clearance of various physiologically peptides like amyloid-beta
      and insulin. This enzyme has been involved in the physiopathology of diabetes and
      Alzheimer's disease. We describe here a series of small molecules discovered by
      screening. Co-crystallization of the compounds with IDE revealed a binding both
      at the permanent exosite and at the discontinuous, conformational catalytic site.
      Preliminary structure-activity relationships are described. Selective inhibition
      of amyloid-beta degradation over insulin hydrolysis was possible. Neuroblastoma
      cells treated with the optimized compound display a dose-dependent increase in
      amyloid-beta levels. 

PMID- 24735646
TI  - Synthesis and evaluation of cyclohexane carboxylic acid head group containing
      isoxazole and thiazole analogs as DGAT1 inhibitors.
AB  - Diacylglycerol acyltransferase 1 (DGAT1) is known to play an important catalytic
      role in the final step of triglyceride biosynthesis. High fat diet fed DGAT1
      knockout mice were resistant to weight gain and exhibited increased insulin and
      leptin sensitivity thereby indicating a plausible role for DGAT1 inhibitors in
      the treatment of obesity. 4-Phenylpiperidine-1-carbonyl cyclohexanecarboxylic
      acid (compound 6, DGAT1 IC50 = 57 nM) has been lately reported as a potent DGAT1
      inhibitor. In our search for newer scaffolds possessing potent DGAT1 activity we
      undertook a systematic diversification of compound 6 to identify a 4-(5
      phenylthiazole-2-carboxamido)cyclohexanecarboxylic acid scaffold. Further linker
      optimization of this scaffold identified compound 9e (DGAT1 IC50 = 14.8 nM) as a
      potent DGAT1 inhibitor. Coupled with its in vitro potency, compound 9e also
      exhibited 112 percent plasma triglyceride reduction at a 3 mpk dose in an oral
      fat tolerance test (FTT) when studied in Swiss mice. 

PMID- 24735647
TI  - Synthesis and biological evaluation of a novel sigma-1 receptor antagonist based
      on 3,4-dihydro-2(1H)-quinolinone scaffold as a potential analgesic.
AB  - The synthesis and sigma-1 receptor (sigma1R) antagonist activity of a new series
      of 3,4-dihydro-2(1H)-quinolinone derivatives are reported. The new compounds were
      evaluated in vitro in sigma-1 and sigma-2 receptor-binding assays in guinea pig
      brain membranes. The structure-activity relationship led us to the promising
      derivative 7-(3-(piperidin-1-yl)propoxy)-1-(4-fluorobenzyl)-3,4-dihydro-2(1H)
      quinolinone (35). The compounds with highest affinity and greatest selectivity
      were further profiled, and compound 35 had a high binding constant for sigma-1
      receptor (Kisigma1 = 1.22 nM) and high sigma-1/2 selectivity (1066-fold). Thus,
      compound 35, which proved to be an antagonist of sigma-1 receptor, emerged as the
      most interesting candidate. In addition, compound 35 exerted dose-dependent anti
      nociceptive effects in the formalin test. These characteristics suggested that
      the potent and selective compound 35 could be a potent candidate for pain
      treatment. 

PMID- 24735648
TI  - Actin binding proteins, spermatid transport and spermiation.
AB  - The transport of germ cells across the seminiferous epithelium is composed of a
      series of cellular events during the epithelial cycle essential to the completion
      of spermatogenesis. Without the timely transport of spermatids during
      spermiogenesis, spermatozoa that are transformed from step 19 spermatids in the
      rat testis fail to reach the luminal edge of the apical compartment and enter the
      tubule lumen at spermiation, thereby arriving the epididymis for further
      maturation. Step 19 spermatids and/or sperms that remain in the epithelium beyond
      stage VIII of the epithelial cycle will be removed by the Sertoli cell via
      phagocytosis to form phagosomes and be degraded by lysosomes, leading to
      subfertility and/or infertility. However, the biology of spermatid transport, in
      particular the final events that lead to spermiation remain elusive. Based on
      recent data in the field, we critically evaluate the biology of spermiation
      herein by focusing on the actin binding proteins (ABPs) that regulate the
      organization of actin microfilaments at the Sertoli-spermatid interface, which is
      crucial for spermatid transport during this event. The hypothesis we put forth
      herein also highlights some specific areas of research that can be pursued by
      investigators in the years to come. 

PMID- 24735649
TI  - Parkin and PINK1: much more than mitophagy.
AB  - Parkinson's disease (PD) is a progressive neurodegenerative disease that causes a
      debilitating movement disorder. Although most cases of PD appear to be sporadic,
      rare Mendelian forms have provided tremendous insight into disease pathogenesis.
      Accumulating evidence suggests that impaired mitochondria underpin PD pathology.
      In support of this theory, data from multiple PD models have linked Phosphatase
      and tensin homolog (PTEN)-induced putative kinase 1 (PINK1) and parkin, two
      recessive PD genes, in a common pathway impacting mitochondrial health, prompting
      a flurry of research to identify their mitochondrial targets. Recent work has
      focused on the role of PINK1 and parkin in mediating mitochondrial autophagy
      (mitophagy); however, emerging evidence casts parkin and PINK1 as key players in
      multiple domains of mitochondrial health and quality control. 

PMID- 24735650
TI  - [D-Ala2, D-Leu5] encephalin (DADLE) reversibly inhibits cellular transcription in
      neurons without causing cell injury.
AB  - [d-Ala(2)-d-Leu(5)]-Enkephalin (DADLE) has shown promising results in protecting
      neurons from damages. However, the mechanism for this protection is still under
      investigation. The current study was carried out to test the hypothesis that
      DADLE may regulate cellular transcription in neurons. SH-SY5Y cells and primary
      cortical neurons were treated with various doses of DADLE for 24-72h. Results
      demonstrated that DADLE, at all doses and time points examined, significantly
      inhibited cellular transcription in both cells without causing cell injury.
      Following recovery for 72h without DADLE in primary neurons, the transcriptional
      activity fully resumed. Delta opioid receptor (DOR) is not involved in this
      process, as Naltrindole could not abolish DADLE's transcriptional inhibitory
      effects. Further studies in primary cortical neurons show that DADLE
      significantly inhibited phosphorylation of Ser2 and Ser5 of the C-terminal domain
      (CTD) of RNA polymerase II. These data indicate that DADLE is able to decrease
      cellular transcription through inhibiting phosphorylation of RNA polymerase II in
      neurons, which may provide mechanistic insight into its reported neuroprotective
      effects, and suggests that it warrants further exploration as a potential
      therapeutic strategy for neuroprotection. 

PMID- 24735651
TI  - Neuroprotective effects of madecassoside against focal cerebral ischemia
      reperfusion injury in rats.
AB  - Madecassoside, a triterpenoid derivative isolated from Centella asiatica,
      exhibits anti-inflammatory and antioxidant activities. We investigated its
      neuroprotective effect against ischemia-reperfusion (I/R) injury in cerebral
      neurons in male Sprague-Dawley rats. Madecassoside (6, 12, or 24mg/kg, i.v.) was
      administered 1h after the start of reperfusion, and neurological deficit score
      and infarct volume were evaluated 24h later. Neuronal apoptosis was assessed by
      performing terminal deoxynucleotidyl transferase-mediated dUTP-nick end labeling
      (TUNEL) staining, and pathological brain damage was estimated by performing
      hematoxylin and eosin staining. Serum levels of malondialdehyde, superoxide
      dismutase activity, reduced glutathione levels, and nitric oxide levels were also
      determined. mRNA and protein expression of pro-inflammatory cytokines
      (Interleukin-1beta/6, and tumor necrosis factor-alpha) were measured by real-time
      RT-PCR and ELISA, respectively; NF-kappaB p65 expression was determined by
      western blotting. Madecassoside significantly reduced brain infarct area,
      resolved neurological deficit, and ameliorated neuronal apoptosis. It also
      significantly reduced the levels of malondialdehyde and nitric oxide, and
      augmented the antioxidant activity in rats subjected to cerebral I/R. Moreover,
      the levels of pro-inflammatory cytokines and NF-kappaB p65 significantly reduced
      after madecassoside treatment. These results indicate that madecassoside is
      neuroprotective and may be useful in reducing the damage caused by stroke. 

PMID- 24735652
TI  - System-on-fluidics immunoassay device integrating wireless radio-frequency
      identification sensor chips.
AB  - A simple and sensitive point-of-care-test (POCT) device for chemiluminescence
      (CL) immunoassay was devised and tested. The device consists of a plastic flow
      channel reactor and two wireless-communication sensor chips, namely, a photo
      sensor chip and a temperature-sensor chip. In the flow-channel reactor, a target
      antigen is captured by an antibody immobilized on the inner wall of the flow
      channel and detected with enzyme labeled antibody by using CL substrate. The CL
      signal corresponding to the amount of antigen is measured by a newly developed
      radio-frequency-identification (RFID) sensor, which enables batteryless operation
      and wireless data communication with an external reader. As for the POCT device,
      its usage environment, especially temperature, varies for each measurement.
      Hence, temperature compensation is a key issue in regard to eliminating dark
      signal fluctuation, which is a major factor in deterioration of the precision of
      the POCT device. A two-stage temperature-compensation scheme was adopted. As for
      the first stage, the signals of two photodiodes, one with an open window and one
      with a sealed window, integrated on the photo-sensor chip are differentiated to
      delete the dark signal. As for the second stage, the differentiated signal
      fluctuation caused by a temperature variation is compensated by using the other
      sensor chip (equipped with a temperature sensor). The dark-level fluctuation
      caused by temperature was reduced from 0.24 to 0.02 pA/ degrees C. The POCT
      device was evaluated as a CL immunoassay of thyroid-stimulating hormone (TSH).
      The flow rate of the CL reagent in the flow channel was optimized. As a result,
      the detection limit of the POCT device was 0.08 ng/ml (i.e., 0.4 MUIU/ml).

PMID- 24735653
TI  - Assessment of longitudinal myocardial mechanics in patients with degenerative
      mitral valve regurgitation predicts postoperative worsening of left ventricular
      systolic function.
AB  - BACKGROUND: The optimal timing of mitral valve repair (MVr) in patients with
      chronic severe degenerative mitral regurgitation (MR) remains controversial and
      is broadly based on either measurable loss of systolic function, as determined by
      left ventricular (LV) ejection fraction (LVEF) and/or LV chamber remodeling. The
      aim of this study was to test the hypothesis that the assessment of LV
      deformation by speckle-tracking echocardiography might uncover subclinical
      changes for predicting reduction of LVEF after MVr. METHODS: One hundred thirty
      patients (mean age, 57 +/- 14 years; 85 men) who underwent MVr for chronic severe
      degenerative MR were retrospectively identified. Baseline and immediate
      postoperative transthoracic echocardiography was used to assess global
      longitudinal strain (GLS), global radial strain, and global circumferential
      strain before and after MVr. RESULTS: In comparison with baseline, MVr resulted
      in significant reductions in LVEF (P < .0001) and in GLS (P < .0001).
      Postoperative change in LVEF was related to the changes in GLS (r = -0.71, P <
      .0001) and global circumferential strain (r = -0.22, P = .01) but not global
      radial strain. For the entire group, the presence of a high preoperative GLS
      magnitude predicted a postoperative reduction in LVEF of >10% (odds ratio, 0.80;
      P < .001). Furthermore, GLS showed diagnostic value in predicting a reduction in
      LVEF of >10% with a resulting postoperative LVEF of <50% (area under the curve,
      0.93; P < .001). CONCLUSIONS: In chronic severe degenerative MR,
      disproportionately higher LV global longitudinal strain signifies a maladaptive
      preload-related change that is associated with substantial loss of LVEF
      immediately after MVr. Preoperative assessment of longitudinal strain may be
      potentially useful for optimizing the timing of MVr for degenerative MR.

PMID- 24735654
TI  - The Roots of Autism and ADHD Twin Study in Sweden (RATSS).
AB  - Neurodevelopmental disorders affect a substantial minority of the general
      population. Their origins are still largely unknown, but a complex interplay of
      genetic and environmental factors causing disturbances of the central nervous
      system's maturation and a variety of higher cognitive skills is presumed. Only
      limited research of rather small sample size and narrow scope has been conducted
      in neurodevelopmental disorders using a twin-differences design. The Roots of
      Autism and ADHD Twin Study in Sweden (RATSS) is an ongoing project targeting
      monozygotic twins discordant for categorical or dimensional autistic and
      inattentive/hyperactive-impulsive phenotypes as well as other neurodevelopmental
      disorders, and typically developing twin controls. Included pairs are 9 years of
      age or older, and comprehensively assessed for psychopathology, medical history,
      neuropsychology, and dysmorphology, as well as structural, functional, and
      molecular brain imaging. Specimens are collected for induced pluripotent (iPS)
      and neuroepithelial stem cells, genetic, gut bacteria, protein-/monoamine, and
      electron microscopy analyses. RATSS's objective is to generate a launch pad for
      novel surveys to understand the complexity of genotype-environment-phenotype
      interactions in autism spectrum disorder and attention-deficit hyperactivity
      disorder (ADHD). By October 2013, RATSS had collected data from 55 twin pairs,
      among them 10 monozygotic pairs discordant for autism spectrum disorder, seven
      for ADHD, and four for other neurodevelopmental disorders. This article describes
      the design, recruitment, data collection, measures, collected pairs'
      characteristics, as well as ongoing and planned analyses in RATSS. Potential
      gains of the study comprise the identification of environmentally mediated
      biomarkers, the emergence of candidates for drug development, translational
      modeling, and new leads for prevention of incapacitating outcomes. 

PMID- 24735655
TI  - Leukotriene receptor antagonist as a novel tocolytic in an in vitro model of
      human uterine contractility.
AB  - OBJECTIVE: This study analyzed the ability of montelukast, a cysteinyl
      leukotrienes receptor antagonist and anti-inflammatory agent, to produce a
      consistent tocolytic effect alone or in combination with nifedipine, a calcium
      (Ca(2+)) channel blocker currently used in clinical practice. STUDY DESIGN:
      Uterine biopsies were obtained from consenting women undergoing elective cesarean
      sections at term (n=20). Myometrial microsomal fractions were analyzed by
      immunoblotting to quantify relative cysteinyl leukotrienes receptor 1 (CysLTR1)
      levels. Isometric tension measurements were performed in vitro on human
      myometrial strips (n=120) in isolated organ baths in order to establish
      concentration-response curves to montelukast and to quantify changes in Ca(2+)
      sensitivity on beta-escin permeabilized tissues. RESULTS: Immunodetection
      analysis revealed the presence of CysLTR1 receptor in uterine tissues, fetal
      membranes and placenta. A significant increase in area under the curve (AUC) was
      quantified following the addition of leukotriene D4 (LTD4) (0.01-0.3 MUM), an end
      product of the lipoxygenase pathway. Conversely, addition of montelukast produced
      a significant tocolytic effect by decreasing the frequency and AUC (IC50=1 MUM).
      Moreover, addition of montelukast also resulted in a reduced Ca(2+) sensitivity
      as compared to control tissues (EC50 values of 654 and 403 nM; p=0.02 at pCa 6),
      while an additive effect was observed in combination with 0.1 nM nifedipine
      (p=0.004). CONCLUSION: This original study demonstrates the potency of
      montelukast as a tocolytic agent in an in vitro human uterine model. Montelukast,
      in combination with nifedipine, could represent a therapeutic approach to reduce
      inflammation associated with prematurity while facilitating the inhibition of
      preterm labor.

PMID- 24735656
TI  - Parental encouragement of healthy behaviors: adolescent weight status and health
      related quality of life.
AB  - BACKGROUND: Obesity is a major health concern for adolescents, with one in four
      being overweight or obese in Australia. The purpose of this study was to examine
      the moderation effect of parental encouragement of healthy behaviors on the
      relationship between adolescent weight status and Health-Related Quality of Life
      (HRQoL). METHODS: Baseline data were collected from 3,040 adolescents
      participating in the It's Your Move project, conducted in the Barwon South-West
      region of Victoria, in 2005. The Paediatric Quality of Life Inventory was used to
      measure HRQoL, and parental encouragement was derived from purposely designed
      self-report items. Weight status was calculated according to World Health
      Organization growth standards from measured weight and height. Linear regression
      analyses modeled direct relationships and interaction terms. Analyses were
      adjusted for age, sex, physical activity level, nutrition and school attended.
      RESULTS: Higher levels of parental encouragement, as compared to low
      encouragement, were positively associated with higher global HRQoL scores,
      particularly in the physical functioning domain. To a lesser degree, high
      parental encouragement was also associated with higher scores on the psychosocial
      domain. Obese weight status showed a significant association with lower HRQoL on
      all scales. Parental encouragement significantly moderated the inverse
      relationship between overweight status and physical wellbeing. CONCLUSIONS:
      Findings suggest that parental encouragement of healthy behavior is associated
      with increased HRQoL scores for adolescents. Whilst more research is needed to
      validate the significant interaction effect, main effects suggest that parental
      encouragement of healthy behavior is an important factor in adolescent wellbeing
      and should be considered when developing prevention and clinical interventions
      for obesity.

PMID- 24735658
TI  - Effect of different superovulation stimulation protocols on adenosine
      triphosphate concentration in rabbit oocytes.
AB  - Ovarian stimulation protocols are used usually to increase the number of oocytes
      collected. The determination of how oocyte quality may be affected by these
      superovulation procedures, therefore, would be very useful. There is a high
      correlation between oocyte ATP concentration and developmental competence of the
      resulting embryo. The aim of this study was to evaluate the effect of follicle
      stimulating hormone (FSH) origin and administration protocols on oocyte ATP
      content. Rabbit does were distributed randomly into four groups: (i) a control
      group; (ii) the rhFSH3 group: females were injected, every 24 h over 3 days, with
      0.6 MUl of rhFSH diluted in polyvinylpyrrolidone (PVP); (iii) the pFSH3 group:
      females were injected every 24 h over 3 days with 11.4 MUg of pFSH diluted in
      PVP; and (iv) the pFSH5 group: females were injected twice a day for 5 days with
      11.4 MUg of pFSH diluted in saline serum. Secondly, the effect of pFSH5 protocol
      on developmental potential was evaluated. Developmental competence of oocytes
      from the control and pFSH5 groups was examined. Differences in superovulation
      treatments were found for ATP levels. In the pFSH5 group, the ATP level was
      significantly lower than that of the other groups (5.63 +/- 0.14 for pFSH group
      versus 6.42 +/- 0.13 and 6.19 +/- 0.15 for rhFSH3 and pFSH3, respectively; P <
      0.05). In a second phase, only 24.28% of pFSH5 ova developed into hatched
      blastocysts compared with 80.39% for the control group. A negative effect on
      oocyte quality was observed in the pFSH5 group in ATP production, it is possible
      that, after this superovulation treatment, oocyte metabolism would be affected. 

PMID- 24735657
TI  - The interplay of DNA methylation over time with Th2 pathway genetic variants on
      asthma risk and temporal asthma transition.
AB  - BACKGROUND: Genetic effects on asthma of genes in the T-helper 2 (Th2) pathway
      may interact with epigenetic factors including DNA methylation. We hypothesized
      that interactions between genetic variants and methylation in genes in this
      pathway (IL4, IL4R, IL13, GATA3, and STAT6) influence asthma risk, that such
      influences are age-dependent, and that methylation of some CpG sites changes over
      time in accordance with asthma transition. We tested these hypotheses in
      subsamples of girls from a population-based birth cohort established on the Isle
      of Wight, UK, in 1989. RESULTS: Logistic regression models were applied to test
      the interaction effect of DNA methylation and SNP on asthma within each of the
      five genes. Bootstrapping was used to assess the models identified. From 1,361
      models fitted at each age of 10 and 18 years, 8 models, including 4 CpGs and 8
      SNPs, showed potential associations with asthma risk. Of the 4 CpGs, methylation
      of cg26937798 (IL4R) and cg23943829 (IL4) changes between ages 10 and 18 (both
      higher at 10; P = 9.14 * 10(-6) and 1.07 * 10(-5), respectively). At age 10, the
      odds of asthma tended to decrease as cg12405139 (GATA3) methylation increased
      (log-OR = -12.15; P = 0.049); this effect disappeared by age 18. At age 18,
      methylation of cg09791102 (IL4R) was associated with higher risk of asthma among
      subjects with genotype GG compared to AG (P = 0.003), increased cg26937798
      methylation among subjects with rs3024685 (IL4R) genotype AA (P = 0.003) or
      rs8832 (IL4R) genotype GG (P = 0.01) was associated with a lower asthma risk;
      these CpGs had no effect at age 10. Increasing cg26937798 methylation over time
      possibly reduced the risk of positive asthma transition (asthma-free at age 10 ->
      asthma at age 18; log-OR = -3.11; P = 0.069) and increased the likelihood of
      negative transition (asthma at age 10 -> asthma-free at age 18; log-OR = 3.97; P
      = 0.074). CONCLUSIONS: The interaction of DNA methylation and SNPs in Th2 pathway
      genes is likely to contribute to asthma risk. This effect may vary with age.
      Methylation of some CpGs changed over time, which may influence asthma
      transition.

PMID- 24735659
TI  - [Proper understanding of aberration and scatter light and reasonable selection of
      IOL].
AB  - Along with the science and technology development, cataract surgery technology
      and the equipment as well as the IOL design and the technique of manufacture al
      had the considerable progress, cataract surgery had transformed into the
      refractive surgery gradually. The imaging quality of IOL eyes had influenced by
      the scatter light, the optical characters of the intraocular refractive mediums
      and the interactions among the different higher order aberrations. Therefore when
      choosing the IOLs, paying attention to many details and depending on the
      different sickness condition to carry on the personalized choice, can enhance
      sickness the degree od satisfaction.

PMID- 24735660
TI  - [Analysis of refractive status after cataract surgery in age-related cataract
      patients with shallow anterior chamber].
AB  - OBJECTIVE: To evaluate the characteristics of postoperative refractive status in
      age-related cataract patients with shallow anterior chamber and the correlation
      between pre-operative anterior chamber depth and postoperative refractive status.
      METHODS: Prospective case-control study. Sixty-eight cases (90 eyes) with age
      related cataract were recruited from October 2010 to January 2012 in People's
      Hospital Peking University including 28 cases (34 eyes) in control group and 40
      cases (56 eyes) in shallow anterior chamber group according to anterior chamber
      depth (ACD) measured by Pentacam system. Axial length and keratometer were
      measured by IOL Master and intraocular lens power was calculated using SRK/T
      formula. Postoperative refraction, ACD and comprehensive eye examination were
      performed at 1 month and 3 months after cataract surgery. Using SPSS13.0 software
      to establish a database, the two groups were compared with independent samples t
      test and correlation analysis were performed with binary logical regression.
      RESULTS: The postoperative refractive deviation at 1 month were (-0.39 +/- 0.62)
      D in control group and (+0.73 +/- 0.26) D in shallow anterior chamber group
      respectively which present statistical significance between the two groups (P =
      0.00, t = 3.67); the postoperative refractive deviation in 3 month was (-0.37 +/-
      0.62) D in control group and (+0.79 +/- 0.28) D in shallow anterior chamber group
      operatively which present statistical significance between the two groups (P =
      0.00, t = 3.33). In shallow anterior chamber group, with the shallower of ACD,
      the greater of refractive deviation (P = 0.00, r1 month = -0.57, r3 months = 
      0.61). CONCLUSION: Hyperopic shift existed in age-related cataract patients with
      shallow anterior chamber and the shallower of ACD was, the greater of hyperopic
      shift happened.

PMID- 24735661
TI  - [Artisan iris claw intraocular lens implantation for the correction of aphakia
      after pars plana vitrectomy].
AB  - OBJECTIVE: To compare the efficacy and complications of Artisan iris claw
      intraocular lens implantation with those of posterior chamber intraocular lens
      implantation with ciliary sulcus suture fixation for correction of aphakia in
      vitrectomized eyes without capsular support. METHODS: This was a prospective
      interventional case series. From Jan 2009 to Feb 2012, 53 aphakic vitrectomized
      eyes without sufficient capsular support were divided into two groups according
      to the condition of residual capsule. Group one:28 eyes received Artisan iris
      claw intraocular lens implantation. Group two: 25 eyes received posterior chamber
      intraocular lens implantation with ciliary sulcus suture fixation. The best
      corrected visual acuity and intraocular pressure, corneal endothelial cell loss
      rate, duration of surgery and complications were compared between two groups. Two
      independent t-test,Mann-Whitney test and chi2 test were used to analyze
      measurement data of normal distribution, non-normal distribution and count data
      respectively. RESULTS: The mean duration of surgery in group one [(11.23 +/-
      1.54) min] was much shorter (t = -26.60, P < 0.05) than that in group two [(31.68
      +/- 3.15) min]. The endothelial cell loss rate of group one were (4.39 +/-
      1.85)%, (4.76 +/- 2.06)% and (6.30 +/- 2.71)% at 3 months, 6 months and 1 year
      after surgery, and the data of group two were (3.92 +/- 1.85)%, (4.33 +/- 1.80)%
      and (5.73 +/- 2.12)% . No statistically significant difference was noted between
      two groups at any time point (t = 0.77,0.66, 0.69; P > 0.05). The best corrected
      visual acuity of group one (0.40, 0.12-0.80) was better than that of group two
      (0.30, 0.08-0.60) at 1 day after surgery(t = -2.16, P < 0.05).However, there was
      no statistically significant difference at 1 month and 3 months after surgery (P
      > 0.05). The intraocular pressure of group two [ (11.63 +/- 2.29) mmHg, 1 mmHg =
      0.133 kPa] was much lower (t = 2.34, P < 0.05) than that of group one [(13.61 +/-
      3.37) mmHg] at 1 day after surgery. There was no statistical significant
      difference at 1 month and 3 months after surgery between two groups(P > 0.05).
      The postoperative complications of group one were anterior uveitis, iris
      depigmentation, pupillary distortion and spontaneous lens dislocation. Those of
      group two were choroidal detachment, intraocular haemorrhage, intraocular lens
      decentration and retinal detachment. CONCLUSIONS: Iris claw intraocular lens
      implantation is a simple, fast, less complications and minimally invasive method
      for the correction of aphakic eyes after vitrectomy. There were on difference in
      stability and safety between these two implantation methods. Due to the
      difference of indication choice, either of them can be a viable complement for
      the other.

PMID- 24735662
TI  - [Comparison study of visual function and patient satisfaction in patients with
      monovision and patients with bilateral multifocal intraocular lenses].
AB  - OBJECTIVE: To compare visual function and patient satisfaction in patients with
      bilateral diffractive multifocal intraocular lenses (IOL) and patients with
      monofocal IOL monovision. METHODS: Prospective nonrandomized controlled study.
      This study comprised consecutive bilateral cataract patients 45 cases (90eyes)
      between January 2011 and March 2012. All cases were divided into two groups:
      multifocal IOL group (23 patients) having implantation of AcrySof ReSTOR
      +3D(SN6AD1) multifocal IOL, monovision group (22 patients) having implantation of
      AcrySof IQ (SN60WF) IOL. Parameters analyzed 3 months postoperatively included
      binocular uncorrected distance, intermediate, and near visual acuities; stereo
      vision;photopic and mesopic contrast sensitivity function without glare.
      Parameters analyzed 6 months postoperatively included spectacle independence;
      subjective visual symptoms; and patient satisfaction. The independent-samples t
      test were used to compare the measure data which met normal distribution. The chi
      square test was applied to compare categorical variables. RESULTS: There were no
      significant differences between groups in bilateral uncorrected distance vision
      (0.13 +/- 0.06, 0.17 +/- 0.19; Z = 1.755, P = 0.086) , intermediate (0.34 +/-
      0.05,0.33 +/- 0.06; Z = -0.821, P = 0.416) , and near vision (0.35 +/- 0.06, 0.41
      +/- 0.09; Z = 2.117, P = 0.051) . There were significant differences between
      groups in stereo vision (Median: 150", 525"; Z = -2.092, P = 0.036) . Percentage
      of patients wearing spectacle were less than 10% in all groups [91.3% (21/23),
      90.9% (20/22) ].On the questionnaire, patients in multifocal IOL group complained
      with double vision, trouble in night vision and halo(21.7%). CONCLUSIONS:
      Pseudophakic monovision and MIOL achieved distance vision, intermediate vision
      and near vision. But monovision was no risk for disturbing visual symptoms
      associated with multifocal IOL.

PMID- 24735663
TI  - [Analysis of the corneal spherical aberration in people with senile cataract].
AB  - OBJECTIVE: To investigate the distribution of the spherical aberration in people
      with senile cataract, in the interest of the customized selection of the
      intraocular lens in cataract surgeries and the future design of the intraocular
      lens. METHODS: Retrospective study. Analysis of 922 eyes from 504 patients over
      60-years-old was made. Patients were subdivided into 3 age groups (153 patients
      of 60-<70 years-old in group 1, 251 patients of 70-<80 years-old in group 2, 100
      patients of 80- <= 90 years-old in group 3). Pentacam anterior segment analyzer
      (OCULUS, Germany) was used to measure the average corneal and posterior surface K
      readings. The Zernike coefficients of corneal spherical aberration was
      calculated. The difference of corneal parameters among each age group was
      compared. RESULTS: The average age of all patients was (73.5 +/- 6.8) years-old.
      The average corneal K-reading was (44.50 +/- 1.39)D and the average K-reading of
      corneal posterior surface was (-6.44 +/- 0.25)D. There was no difference among 3
      age groups (F = 0.738 and 0.373 retrospectively, P > 0.05). The corneal and
      posterior surface average K-readings had no correlation with the age. The average
      spherical aberration of anterior corneal surface was (0.361 +/- 0.122)um in group
      1, (0.401 +/- 0.139)um in group 2 and (0.440 +/- 0.145)um in group 3
      respectively. The spherical aberration of posterior corneal surface was (-0.122
      +/- 0.035)um, (-0.105 +/- 0.040)um and (-0.090 +/- 0.043)um respectively. The
      total corneal spherical aberration was (0.360 +/- 0.142)um, (0.421 +/- 0.158)um
      and (0.476 +/- 0.170)um respectively. Significant differences were observed among
      3 age groups (F = 10.561, 20.937 and 17.257 retrospectively, P < 0.01). The
      spherical aberrations of the corneal anterior, posterior surface and total cornea
      had positive correlation with the age (r = 0.203, 0.288 and 0.258 respectively, P
      < 0.01). The corneal spherical aberrations had no differences between right and
      left eyes, and had significant positive correlation between both sides.
      CONCLUSIONS: The people with senile cataract over 60-year-old had higher corneal
      spherical aberrations than other age. The corneal spherical aberrations increased
      with the age and had significant correlation inter-ocularly.

PMID- 24735664
TI  - [Analysis of outcomes of secondary intraocular lens implantation in open-globe
      injury after vitrectomy].
AB  - OBJECTIVE: To explore the time and method of secondary intraocular lens (IOL)
      implantation in open-globe injury after vitrectomy and to analyze the efficacies
      and relative factors of the treatment. METHODS: This is a retrospective case
      series study. Clinical data of 78 eyes of 78 patients with open-globe injury who
      underwent secondary IOL implantation after vitrectomy in Tianjin Medical
      University General Hospital from 2007 to 2012 were analyzed. There were 27 eyes
      of 27 patients with penetrating injury, 36 eyes of 36 patients with intraocular
      foreign body (IFB), 4 eyes of 4 patients with ocular rupture, and 11 eyes of 11
      patients with endophthalmitis. The IFB included magnetic foreign body in 23 eyes
      of 23 patients, glass foreign body in 6 eyes of 6 patients, and eyelash foreign
      body in 7 eyes of 7 patients. Thirty-one eyes of 31 patients were tamponade with
      silicone oil, and 47 eyes of 47 patients were tamponade with C3F8 during
      vitrectomy. The methods of IOL implantation included posterior chamber IOL
      implantation in 32 eyes of 32 patients and sulcus-fixed IOL implantation in 46
      eyes of 46 patients. The examinations before IOL implantation mainly included
      visual acuity, slit lamp biomicroscope, direct and indirect ophthalmoscope,
      visual electrophysiology, corneal endothelium, B scan, ultrasound biomicroscope
      and intraocular pressure. Four eyes of 4 patients underwent suturing of
      peripheral iris, and 5 eyes of 5 patients underwent suturing of iris laceration.
      The visual acuity ranged from light perception to 0.1 before vitrectomy. The mean
      follow-up time was 15 +/- 3 months with a range from 6 to 36 months. RESULTS: The
      mean interval between IOL implantation and vitrectomy was 2.5 +/- 0.2 months with
      a range from 1.5 to 6 months. The best corrected visual acuity was from 0.1 to
      1.0 after vitrectomy. The uncorrected visual acuity ranged from 0.1 to 0.8, and
      the best corrected visual acuity was from 0.1 to 1.0 after IOL implantation. The
      postoperative complications mainly included mild anterior chamber exudates in 4
      eyes of 4 patients, temporary intraocular pressure elevation in 7 eyes of 7
      patients, and recurrent retinal detachment in 2 eyes of 2 patients. CONCLUSIONS:
      The appropriate interval of secondary IOL implantation in open-globe injury after
      vitrectomy is important. Posterior chamber IOL implantation is performed in eyes
      with integrity of posterior capsule, and IOL sutured in the sulcus in eyes
      without posterior capsule support. It is safe and effective for secondary IOL
      implantation in open-globe injury after vitrectomy.

PMID- 24735665
TI  - [Meta-analysis of clinical randomized controlled trials comparing refractive with
      diffractive multifocal intraocular lenses in cataract surgery].
AB  - OBJECTIVE: To systematic review the effectiveness of refractive multifocal
      intraocular lens (MIOL) versus diffractive MIOL in the treatment of cataract.
      METHOD: Randomized controlled trials comparing refractive MIOL with diffractive
      MIOL were identified by searching PubMed (1966 to May, 2013), EMbase (1980 to
      May, 2013), Medline (1966 to May, 2013), and The Cochrane Library (Issue 1,
      2013). We also hand-searched related journals. All the searches were restricted
      in English or Chinese. Methodological quality of randomized controlled trials
      (RCT) was evaluated by simple evaluate method that recommended by the Cochrane
      Collaboration. Data extracted by two reviewers with designed extraction form.
      RevMan software (release 5.2) was used for data management and analysis. RESULTS:
      A total of 11 trials (1460 eyes) were included for systematic review. Subgroup
      analyses were used according to different model comparison of MIOL. The results
      showed a significant difference in the mean of the uncorrected distance visual
      acuity (UCDVA) and the uncorrected intermediate visual acuity (UCIVA) in the
      refractive MIOL group with WMD -0.04, 95%CI -0.06 to -0.03 (P < 0.01) and WMD 
      0.05, 95%CI -0.09 to -0.02 (P = 0.001). It showed a significantly difference in
      the mean of the uncorrected near visual acuity (UCNVA), complete spectacle
      independent rate, halo rate and glare rate in the diffractive MIOL group with WMD
      0.11, 95%CI 0.08 to 0.15 (P < 0.01), WMD 2.98, 95%CI 2.17 to 4.09 (P < 0.01), WMD
      1.52, 95%CI 1.14 to 2.04 (P = 0.004) and WMD 1.27, 95%CI 1.07 to 1.50 (P =
      0.005). There was no significant difference between the two groups in the mean of
      the best corrected distance visual acuity (BCDVA), the best distance corrected
      intermediate visual acuity (BDCIVA), the best distance corrected near visual
      acuity (BDCNVA) and the best corrected near visual acuity (BCNVA) with WMD -0.01,
      95%CI -0.03 to 0.01 (P = 0.45), WMD -0.06, 95%CI -0.15 to 0.03 (P = 0.18), WMD
      0.08, 95%CI -0.01 to 0.17 (P = 0.09) and WMD -0.02, 95%CI -0.26 to 0.23 (P =
      0.88). CONCLUSIONS: Patients implanted with refractive MIOL show better
      uncorrected distance and intermediate visual acuity; patients implanted with
      diffractive MIOL show better uncorrected near visual acuity with less likely to
      appear light halo, glare and other visual adverse reactions. As for spectacles
      correction cases, patients implanted with diffractive or refractive MIOL have
      considerable performances in the far, middle, near visual acuity.

PMID- 24735666
TI  - [Clinical observation of the vitreous surgery for open-globe injuries in
      different timing after the trauma].
AB  - OBJECTIVE: To evaluate the clinical efficacy and influential factors of
      vitrectomy for open-globe injuries in different timing. METHODS: Prospective
      cohort study. The clinical effect and complication of the vitrectomy performed by
      the same surgeon for open-globe injury in different timing (2-4 d or 10-14 d)
      from April 2011 to January 2013 were compared.Emergent intraocular surgeries such
      as intraocular foreign body and traumatic endophthalmitis were excluded. RESULT:
      A total of 33 patients (33 eyes) were included in the study with 15 cases in the
      early group (2-4 d) and 18 cases in routine group (10-14 d). The rate of retinal
      re-attachment showed that 11 of 13 eyes that had retinal detachment were re
      attached in the early group.One of 13 eyes had retinal re-attachment after the
      second surgery and 1 eye failed to re-attach.Five of 15 eyes with retinal
      detachment had retina re-attached in the routine group. Four of 15 eyes had
      retina re-attached after second surgery and 6 eyes failed to re-attach. There was
      a statistical significance between the two groups (U = 46.500, Z = -2.638, P =
      0.008). The eye-globe saving rate had no statistical significance (chi2 = 3.48, P
      = 0.095).Fourteen eyes had been saved and 1 eye failed to have vitrectomy in the
      early group. Twelve eyes had been saved and 6 eyes failed to have vitrectomy in
      the routine group. The incidence of traumatic proliferative vitreo
      retinopathy(TPVR) had statistical significance between the two groups (chi2 =
      12.34, P = 0.001).One eye occurred TPVR in the early group and 12 eyes occurred
      TPVR in the routine group. The visual acuity recovery showed that patients in the
      early group had better vision recovery than patients in the routine group (U =
      61.500,Z = -2.858, P = 0.004). Complications like intraoperative bleeding and
      postoperative infection had no significant difference between the two groups.
      CONCLUSION: Cases performing vitrectomy earlier had relatively good prognosis.

PMID- 24735667
TI  - [Evaluation of LOXL1 polymorphisms in exfoliation syndrome in the Uygur
      population].
AB  - OBJECTIVE: In this study, we evaluate the association profiles of the lysyl
      oxidase-like 1 ( LOXL1) gene polymorphisms with exfoliation syndrome in XFS Uygur
      population. METHODS: Case-control study. Sixty-four unrelated Uygur patients with
      XFS (including 7 patients with Exfoliation Syndrome Glaucoma) and 127 Uygur
      control subjects were included. All of control subjects were selected from the
      same area, passed through the same ophthalmic checks and confirmed without any
      expressions of XFS. Most of them suffered from cataract and other ophthalmic
      disease.Genotypes of the three single nucleotide polymorphisms (SNPs) of LOXL1
      (rs1048661, rs2165241 and rs3825942) were analyzed by direct sequencing following
      PCR amplification, and a case-control association study was performed and judged
      by odd ratio (OR) with (95% confidential interval). RESULTS: G allele of
      rs1048661 [OR:1.92 (1.14-3.22)], G of rs3825942 [OR:4.86 (2.02-11.68)], and T of
      rs2165241[OR:3.98 (2.54-6.25)] were risk alleles for the disorder. The genotypes
      TT for rs2165241 [OR:2.20 (1.04-4.65)] were risk genotypes for the disease.
      CONCLUSION: LOXL1 is a susceptibility gene of XFS in the Uygur populations. The
      risk alleles of rs1048661, rs3825942 and rs2165241 in Uygur subjects were
      identified to be significantly associated with XFS individually.

PMID- 24735668
TI  - [Early experience of femtosecond laser assisted cataract surgery].
AB  - Femtosecond assisted phacoemulsification is being used in clinic widely. There
      have been many reports about its safety and effectiveness. In our country,
      femtophaco is launching and being developed gradually. The early clinical results
      and experiences showed that femtosecond lasers assisted cataract surgery had less
      complications and good repeatability with a much shorter learning curve. More
      importantly, it provided a standardized and precise platform and would become a
      milestone in the technology renovation of cataract surgery. 

PMID- 24735669
TI  - [The research advances of the perioperative pharmaceutical prophylaxis for
      postoperative endophthalmitis following cataract surgery].
AB  - Postoperative endophthalmitis (PE) is the most dangerous complications of the
      cataract surgery. The incidence of PE is low, but the consequence is always
      devastating. The cataract surgeon paid much more attention on the prophylaxis of
      PE.Research results have been achieved in the different periods of
      perioperation.We reviewed the research literatures of infective routes, causative
      organisms, preoperative use of topical antibiotics and antiseptics,
      intraoperative and/or postoperative delivery of antibiotics. 

PMID- 24735670
TI  - Hospital trust reviews care provided to 88 patients by oral and maxillofacial
      surgeon.

PMID- 24735671
TI  - Talking in Fury: The Cortico-Subcortical Network Underlying Angry Vocalizations.
AB  - Although the neural basis for the perception of vocal emotions has been described
      extensively, the neural basis for the expression of vocal emotions is almost
      unknown. Here, we asked participants both to repeat and to express high-arousing
      angry vocalizations to command (i.e., evoked expressions). First, repeated
      expressions elicited activity in the left middle superior temporal gyrus (STG),
      pointing to a short auditory memory trace for the repetition of vocal
      expressions. Evoked expressions activated the left hippocampus, suggesting the
      retrieval of long-term stored scripts. Secondly, angry compared with neutral
      expressions elicited activity in the inferior frontal cortex IFC and the dorsal
      basal ganglia (BG), specifically during evoked expressions. Angry expressions
      also activated the amygdala and anterior cingulate cortex (ACC), and the latter
      correlated with pupil size as an indicator of bodily arousal during emotional
      output behavior. Though uncorrelated, both ACC activity and pupil diameter were
      also increased during repetition trials indicating increased control demands
      during the more constraint production type of precisely repeating prosodic
      intonations. Finally, different acoustic measures of angry expressions were
      associated with activity in the left STG, bilateral inferior frontal gyrus, and
      dorsal BG. 

PMID- 24735672
TI  - Correlation Between Activation of the Prelimbic Cortex, Basolateral Amygdala, and
      Agranular Insular Cortex During Taste Memory Formation.
AB  - Conditioned taste aversion (CTA) is a well-established learning paradigm, whereby
      animals associate tastes with subsequent visceral illness. The prelimbic cortex
      (PL) has been shown to be involved in the association of events separated by
      time. However, the nature of PL activity and its functional network in the whole
      brain during CTA learning remain unknown. Here, using awake functional magnetic
      resonance imaging and fiber tracking, we analyzed functional brain connectivity
      during the association of tastes and visceral illness. The blood oxygen level
      dependent (BOLD) signal significantly increased in the PL after tastant and
      lithium chloride (LiCl) infusions. The BOLD signal in the PL significantly
      correlated with those in the amygdala and agranular insular cortex (IC), which we
      found were also structurally connected to the PL by fiber tracking. To precisely
      examine these data, we then performed double immunofluorescence with a neuronal
      activity marker (c-Fos) and an inhibitory neuron marker (GAD67) combined with a
      fluorescent retrograde tracer in the PL. During CTA learning, we found an
      increase in the activity of excitatory neurons in the basolateral amygdala (BLA)
      or agranular IC that project to the PL. Taken together, these findings clearly
      identify a role of synchronized PL, agranular IC, and BLA activity in CTA
      learning. 

PMID- 24735673
TI  - LSD1 Neurospecific Alternative Splicing Controls Neuronal Excitability in Mouse
      Models of Epilepsy.
AB  - Alternative splicing in the brain is dynamic and instrumental to adaptive changes
      in response to stimuli. Lysine-specific demethylase 1 (LSD1/KDM1A) is a
      ubiquitously expressed histone H3Lys4 demethylase that acts as a transcriptional
      co-repressor in complex with its molecular partners CoREST and HDAC1/2. In
      mammalian brain, alternative splicing of LSD1 mini-exon E8a gives rise to
      neuroLSD1, a neurospecific isoform that, upon phosphorylation, acts as a dominant
      negative causing disassembly of the co-repressor complex and de-repression of
      target genes. Here we show that the LSD1/neuroLSD1 ratio changes in response to
      neuronal activation and such effect is mediated by neurospecific splicing factors
      NOVA1 and nSR100/SRRM4 together with a novel cis-silencer. Indeed, we found that,
      in response to epileptogenic stimuli, downregulation of NOVA1 reduces exon E8a
      splicing and expression of neuroLSD1. Using behavioral and EEG analyses we
      observed that neuroLSD1-specific null mice are hypoexcitable and display
      decreased seizure susceptibility. Conversely, in a mouse model of Rett syndrome
      characterized by hyperexcitability, we measured higher levels of NOVA1 protein
      and upregulation of neuroLSD1. In conclusion, we propose that, in the brain,
      correct ratio between LSD1 and neuroLSD1 contributes to excitability and, when
      altered, could represent a pathogenic event associated with neurological
      disorders involving altered E/I. 

PMID- 24735674
TI  - Long-Term Synaptic Plasticity in Rat Barrel Cortex.
AB  - Rats generate sweeping whisker movements in order to explore their environments
      and identify objects. In somatosensory pathways, neuronal activity is modulated
      by the frequency of whisker vibration. However, the potential role of rhythmic
      neuronal activity in the cerebral processing of sensory signals and its mechanism
      remain unclear. Here, we showed that rhythmic vibrissal stimulation with short
      duration in anesthetized rats resulted in an increase or decrease in the
      amplitude of somatosensory-evoked potentials (SEPs) in the contralateral barrel
      cortex. The plastic change of the SEPs was frequency dependent and long lasting.
      The long-lasting enhancement of the vibrissa-to-cortex evoked response was side-
      but not barrel-specific. Local application of dl-2-amino-5-phosphonopentanoic
      acid into the barrel cortex revealed that this vibrissa-to-cortex long-term
      plasticity in adult rats was N-methyl-d-aspartate receptor-dependent. Most
      interestingly, whisker trimming through postnatal day (P)1-7 but not P29-35
      impaired the long-term plasticity induced by 100 Hz vibrissal stimulation. The
      short period of rhythmic vibrissal stimulation did not induce long-lasting
      plasticity of field potentials in the thalamus. In conclusion, our results
      suggest that natural rhythmic whisker activity modifies sensory information
      processing in cerebral cortex, providing further insight into sensory perception.

PMID- 24735675
TI  - Technological and practical challenges of dry powder inhalers and formulations.
AB  - In the 50 years following the introduction of the first dry powder inhaler to the
      market, several developments have occurred. Multiple-unit dose and multi-dose
      devices have been introduced, but first generation capsule inhalers are still
      widely used for new formulations. Many new particle engineering techniques have
      been developed and considerable effort has been put in understanding the
      mechanisms that control particle interaction and powder dispersion during
      inhalation. Yet, several misconceptions about optimal inhaler performance manage
      to survive in modern literature. It is, for example still widely believed that a
      flow rate independent fine particle fraction contributes to an inhalation
      performance independent therapy, that dry powder inhalers perform best at 4 kPa
      (or 60 L/min) and that a high resistance device cannot be operated correctly by
      patients with reduced lung function. Nevertheless, there seems to be a great
      future for dry powder inhalation. Many new areas of interest for dry powder
      inhalation are explored and with the assistance of new techniques like
      computational fluid dynamics and emerging particle engineering technologies, this
      is likely to result in a new generation of inhaler devices and formulations, that
      will enable the introduction of new therapies based on inhaled medicines.

PMID- 24735676
TI  - Dry powders for oral inhalation free of lactose carrier particles.
AB  - Dry powder inhaler (DPI) products have traditionally comprised a simple
      formulation of micronised drug mixed with a carrier excipient, typically lactose
      monohydrate. The presence of the carrier is aimed at overcoming issues of poor
      flowability and dispersibility, associated with the cohesive nature of small,
      micronised active pharmaceutical ingredient (API) particles. Both the powder
      blend and the DPI device must be carefully designed so as to ensure detachment of
      the micronised drug from the carrier excipient on inhalation. Over the last two
      decades there has been a significant body of research undertaken on the design of
      carrier-free formulations for DPI products. Many of these formulations are based
      on sophisticated particle engineering techniques; a common aim in formulation
      design of carrier-free products being to reduce the intrinsic cohesion of the
      particles, while maximising dispersion and delivery from the inhaler. In tandem
      with the development of alternative formulations has been the development of
      devices designed to ensure the efficient delivery and dispersion of carrier-free
      powder on inhalation. In this review we examine approaches to both the powder
      formulation and inhaler design for carrier-free DPI products. 

PMID- 24735677
TI  - Challenges faced by multidisplinary new investigators on addressing grand
      challenges in global health.
AB  - BACKGROUND: The grand challenges approach aims to spark innovative and
      transformative strategies to overcome barriers to significant global health
      issues. Grand Challenges Canada endorses an 'Integrated InnovationTM' approach
      that focuses on the intersection of scientific/technological, social and business
      innovation. In this article we explore themes emerging from a dialogue between
      the authors, who are multidisciplinary recipients of the 'Rising Stars in Global
      Health' award from Grand Challenges Canada, regarding benefits of engaging in
      integrated innovation research, and recommendations for how this approach may
      develop in the future. DISCUSSION: Our dialogue followed a semi-structured
      interview format that addressed three topics: 1) reflections on applying an
      Integrated InnovationTM approach for global health; 2) thoughts on participation
      in the Grand Challenges 2012 meeting; and 3) authors' visions of Grand Challenges
      Canada and the Grand Challenge movement towards 2020. The dialogue was
      transcribed verbatim and we used thematic analysis techniques to identify,
      analyze and report themes in the data. Benefits of working using the Grand
      Challenges approach centered on two themes: a) the potential for scientific
      breakthrough and b) building interdisciplinary collaborations and a community of
      scholars. Challenges and opportunities for Grand Challenges in moving forward
      included: a) capacity building, particularly regarding Integrated InnovationTM
      and scale-up planning; b) interdisciplinary and international mentorship for new
      investigators; and c) potential for future commercialization. CONCLUSIONS: Our
      discussion highlighted that Integrated InnovationTM offers the opportunity to
      develop new theories, methods and approaches to global health while
      simultaneously fostering a collaborative spirit grounded in international,
      interdisciplinary collaborations. However, the arguable over-emphasis on
      corporatization poses a major challenge for new investigators. We propose a more
      balanced way forward that can harness technology to foster mentorship across time
      and space to support the development of such skills and ideas among new
      investigators.

PMID- 24735678
TI  - Increasing phytoremediation efficiency and reliability using novel omics
      approaches.
AB  - Phytoremediation is a cost-effective green alternative to traditional soil
      remediation technologies, but has experienced varied success in practice. The
      recent omics revolution has led to leaps in our understanding of soil microbial
      communities and plant metabolism, and some of the conditions that promote
      predictable activity in contaminated soils and heterogeneous environments.
      Combinations of omics tools and new bioinformatics approaches will allow us to
      understand integrated activity patterns between plants and microbes, and
      determine how this metaorganism can be modified to maximize growth, appropriate
      assembly of microbial communities, and, ultimately, phytoremediation activity.
      Here we provide an overview of how new omics-mediated discoveries can potentially
      be translated into an effective and reliable environmental technology. 

PMID- 24735679
TI  - Post-pandemic assessment of public knowledge, behavior, and skill on influenza
      prevention among the general population of Beijing, China.
AB  - BACKGROUND: The aim of this study was to assess the knowledge, behavioral, and
      skill responses toward influenza in the general population of Beijing after
      pandemic influenza A (H1N1) 2009. METHODS: A cross-sectional study was conducted
      in Beijing, China, in January 2011. A survey was conducted in which information
      was collected using a standardized questionnaire. A comprehensive evaluation
      index system of health literacy related to influenza was built to evaluate the
      level of health literacy regarding influenza prevention and control among
      residents in Beijing. RESULTS: Thirteen thousand and fifty-three valid
      questionnaires were received. The average score for the sum of knowledge,
      behavior, and skill was 14.12+/-3.22, and the mean scores for knowledge,
      behavior, and skill were 4.65+/-1.20, 7.25+/-1.94, and 2.21+/-1.31, respectively.
      The qualified proportions of these three sections were 23.7%, 11.9%, and 43.4%,
      respectively, and the total proportion with a qualified level was 6.7%. There
      were significant differences in health literacy level related to influenza among
      the different gender, age, educational level, occupational status, and location
      groups (p<0.05). There was a significant association between knowledge and
      behavior (r=0.084, p<0.001), and knowledge and skill (r=0.102, p<0.001).
      CONCLUSIONS: The health literacy level remains low among the general population
      in Beijing and the extent of relativities in knowledge, behavior, and skill about
      influenza was found to be weak. Therefore, improvements are needed in terms of
      certain aspects, particularly for the elderly and the population of rural
      districts. Educational level, as a significant factor in reducing the spread of
      influenza, should be considered seriously when intervention strategies are
      implemented.

PMID- 24735680
TI  - Early elevations in pump power with the HeartMate II left ventricular assist
      device do not predict late adverse events.
AB  - BACKGROUND: The aim of this study was to evaluate the prevalence of early pump
      power elevation events in patients with the HeartMate II (HMII) and its impact on
      subsequent development of stroke and pump thrombosis. METHODS: We analyzed
      >45,000 measurements of pump power and pump speed measured during the initial
      hospitalization period and >12,000 follow-up measurements obtained from 138
      consecutive patients implanted with a HMII between January 2009 and December
      2012. An early power elevation (PEL) event was defined as power >=10 W within the
      first 14 post-operative days. Patients were divided into two groups: those with
      an early PEL event and those without (NP). RESULTS: Median follow-up duration was
      316 (range 2 to 1,264) days. Twenty-seven (20%) patients had early PEL events
      that lasted for a total duration of 4 (range 1 to 77) hours per patient. Pump
      speed averaged 9,400 rpm in both groups. Although patients in the PEL group had
      higher median power (7.1 [6.0 to 9.9] W vs 6.7 [5.7 to 7.8] W, p < 0.001) in the
      immediate post-operative period, there was no difference between the two groups
      noted at first follow-up (6.6 [5.9 to 8.7] W vs 6.7 [5.5 to 7.7] W, p = 0.940).
      No differences in the prevalence of hemorrhagic stroke (4% vs 3%, p = 0.56),
      ischemic stroke (0% vs 4%, p = 0.41), hemolysis (7% vs 5%, p = 0.32), pump
      thrombosis (7% vs 4%, p = 0.21) or survival (76% at 1 year in both groups) were
      found between the two groups. CONCLUSIONS: In this single-center experience, PEL
      events that occurred early all resolved by discharge. No relationship was found
      between early PEL events and subsequent development of pump thrombosis,
      hemorrhagic stroke or ischemic stroke.

PMID- 24735681
TI  - Imaging findings of skeletal muscle lymphoma.
AB  - Muscle lymphoma (ML) is a very rare disorder. Its frequency varies and is
      reported to be 0.1-1.4% of all extranodal lymphomas. ML can develop either as
      primary extranodal intramuscular lymphoma or as intramuscular manifestation of
      disseminated disease. There are only few reports describing radiological features
      of ML. Therefore, the aim of this review was to provide statistical data and to
      summarize imaging findings of this rare entity. 

PMID- 24735682
TI  - Pulmonary arterial enlargement in patients with acute exacerbation of
      interstitial pneumonia.
AB  - The purpose of this study was to evaluate change in the size of the main
      pulmonary (PA) artery in patients with acute exacerbation of interstitial
      pneumonia (IP). Twenty-nine patients underwent computed tomography at baseline
      and at the time of acute IP exacerbation for the measurement of the diameters of
      the main PA and the ascending aorta. We found that the diameter of the main PA
      was significantly larger at the time of acute IP exacerbation than at baseline,
      which might reflect the alterations in pulmonary circulation. 

PMID- 24735683
TI  - CT features in uterine necrosis of unknown cause: a case report.
AB  - Uterine necrosis is a rare life-threatening condition known to be related to
      cesarean section, endometritis or uterine artery embolization. We present a case
      of uterine necrosis not preceded by common causative factors, diagnosed by
      computed tomography (CT) in a 64-year-old woman with myelodysplastic syndrome. A
      gas-filled, nonenhancing uterus was noted, diagnostic of uterine necrosis. At
      laparotomy, a nonvital uterus was removed. Imaging findings of uterine necrosis
      have sparsely been reported and mostly focus on magnetic resonance imaging
      technique. In this report, we describe the CT findings of uterine necrosis.

PMID- 24735684
TI  - Mechanism of and relation between the sorption and desorption of nonylphenol on
      black carbon-inclusive sediment.
AB  - Correlation between the sorption and desorption of nonylphenol (NP) and binary
      linear regression were conducted to reveal the underlying mechanism of and
      relation between sorption domains and desorption sites in black carbon (BC)
      amended sediment. The sorption and desorption data could be fitted well using
      dual-mode (R(2) = 0.971-0.996) and modified two-domain model (R(2) = 0.986
      0.995), respectively, and there were good correlations between these two parts of
      parameters (R(2) = 0.884-0.939, P < 0.01). The NP percentage in desorbable
      fraction was almost equal to that of the partition fraction, suggesting the
      desorbed NP came from linear partition domain, whereas the resistant desorption
      NP was segregated in nonlinear adsorption sites, which were dominated by pores in
      BC-amended sediment. Our investigation refined theory about the relation between
      sorption domains and desorption sites in sediment and could be used to predict
      the release risk of NP using sorption data when BC is used for NP pollution
      control. 

PMID- 24735685
TI  - Differences in clinical chemistry values according to the use of two laxatives
      for colonoscopy.
AB  - OBJECTIVES: Polyethylene glycol-electrolyte lavage solutions (PEG-ELSs) and
      sodium phosphate formulations (NaPs) are two major colon cleansing laxatives used
      in preparation for endoscopic examinations of the gastrointestinal tract. PEG
      ELSs are osmotically balanced preparations, whereas NaPs are hyperosmotic
      purgatives. This study aimed to evaluate the effects of these two laxatives on
      routine chemistry tests. DESIGN AND METHODS: We retrospectively reviewed 9366
      clinical records of patients who had health checkups with or without colonoscopy
      from July 2010 to June 2011. We compared the values of 19 clinical chemistry
      parameters in the NaPs group (n=3239) and the PEG-ELSs group (n=1279) with those
      of controls (without colonoscopy, n=4848). RESULTS: Compared with controls, the
      NaPs group had higher mean values of inorganic phosphate, sodium, chloride,
      creatinine, total protein, AST, and ALT, and lower mean values of calcium and
      potassium, exceeding acceptable biases. Notably, inorganic phosphate showed the
      largest % bias (51.14%). In the PEG-ELSs laxative group, higher mean values of
      inorganic phosphorus, creatinine, uric acid, AST, and total bilirubin and a lower
      mean value of potassium were observed compared with controls, exceeding
      acceptable biases. The effects of NaPs on inorganic phosphate, calcium, and
      electrolyte levels exceeded those of PEG-ELSs. CONCLUSIONS: PEG-ELSs rather than
      NaPs are recommended as the first choice for bowel preparation, taking safety
      concerns and the reliability of laboratory values into account. Blood chemistry
      data from blood samples drawn after the ingestion of laxatives for colonoscopy
      should be interpreted with caution.

PMID- 24735686
TI  - Psychosocial predictors of salivary cortisol among older adults with depression.
AB  - ABSTRACT Background: Previous studies have identified a number of psychosocial
      risk factors of dysregulated cortisol (frequently referred to as the "stress
      hormone") among older adults with depression. However, these studies have
      typically only examined a handful of risk factors at a time and have sometimes
      yielded inconsistent results. Method: This study aims to address this gap in the
      literature by simultaneously examining a range of relevant psychosocial
      predictors of diurnal cortisol among 54 older adults with a depressive disorder.
      Salivary cortisol was assessed upon awakening, at 5 PM, and at 9 PM across two
      consecutive days. Participants also completed measures of global psychosocial
      stress, current psychiatric symptomatology, pervasive distress (e.g. history of
      past depression), and protective factors (e.g. social support, resiliency, extent
      to which one has "made sense" of a significant stressor). Results: High levels of
      current depressive symptoms, psychiatric comorbidities, past depressive episodes,
      trait anxiety, and poorer ability to make sense of one's stress were found to be
      associated with flatter (more abnormal) cortisol slopes. However, when all of
      these variables were entered simultaneously in a multiple regression analysis,
      only history of past depression and the degree of sense made of stress emerged as
      unique predictors of cortisol in the model. Conclusions: These findings have
      important implications for identifying depressed elderly individuals with
      dysregulated cortisol patterns who may be most at risk for health complications.
      Treatments that aim to limit the chronicity of depression and help to increase
      the sense made of stress could potentially have a positive impact on health.

PMID- 24735687
TI  - "We no longer live in the old days": a qualitative study on the role of
      masculinity and religion for men's views on violence within marriage in rural
      Java, Indonesia.
AB  - BACKGROUND: Previous studies on domestic violence in Indonesia have focused
      primarily on women's experiences and little research has been undertaken to
      understand men's views on domestic violence or their involvement in the
      prevention of domestic violence. This study aimed to explore men's views on
      masculinity and the use of violence within marriage, in order to gain knowledge
      on how to involve men in prevention of domestic violence in rural Indonesia.
      METHODS: Focus group discussions with six groups of local male community leaders
      in Purworejo were conducted. The discussions were transcribed and coded for the
      construction of a positional map on different masculinities and their relation to
      the level of acceptance of domestic violence. RESULTS: Social and cultural
      changes have played a crucial role in transforming the relationship between men
      and women in Indonesian society. Three different positions of masculinity with
      certain beliefs on the gender order and acceptance of violence within marriage
      were identified: the traditionalist, the pragmatist, and the egalitarian. The
      traditionalist had the highest acceptance of violence as a tool to uphold the
      superior position of men within marriage, while the pragmatist viewed violence as
      undesirable but sometimes needed in order to correct the wife's behavior. The
      egalitarian did not see any reason for violence because they believed that men
      and women are equal and complementary to each other. CONCLUSIONS: Adaptation to
      social and cultural changes combined with lack of exposures to contextual and
      progressive religious teachings has led to the formation of three different
      positions of masculinity among the population in this study. Each position has
      certain beliefs regarding the gender order and the use of violence within
      marriage. Religion is an extremely important aspect that must be included in
      every type of intervention with this population.

PMID- 24735688
TI  - Association between physical and motor development in childhood: a longitudinal
      study of Japanese twins.
AB  - Length and weight in infancy are associated with neurodevelopment, but less is
      known about growth in other anthropometric measures. In this study we analyzed
      how the development in length, weight, head circumference, and chest
      circumference over infancy is associated with motor development in early
      childhood, using a twin study design. Information on physical development over
      infancy and the age at achievement of eight developmental milestones over early
      childhood was collected for 370 Japanese twin pairs. Linear mixed models were
      used to analyze how physical development is associated with motor development
      between individual twins, as well as within twin pairs, adjusting the results for
      shared maternal and postnatal environmental factors. Delayed motor development
      was associated with smaller body size over infancy, and we also found some
      suggestive evidence that it was associated with catch-up growth as well. When
      studying the associations within twin pairs discordant for motor development,
      similar associations were found. However, chest circumference showed the most
      robust association within discordant twin pairs. Smaller body size and rapid
      catch-up growth are associated with delayed motor development. When studying
      these associations within twin pairs and thus adjusting the results for
      gestational age as well as many other maternal and postnatal environmental
      factors, chest circumference showed the most robust association. Chest
      circumference, rarely used in developed countries, can offer additional
      information on prenatal conditions relevant for further motor development not
      achieved by more traditional anthropometric measures. 

PMID- 24735689
TI  - [Building upon the Canadian Journal of Public Health's long tradition of
      excellence to enhance quality and relevance].

PMID- 24735690
TI  - Patterns of cigarillo use among Canadian young adults in two urban settings.
AB  - OBJECTIVES: Current estimates indicate that cigarillo use has become commonplace
      among young adults in Canada despite the established risks to health. However,
      little else is known about patterns of cigarillo use in this subpopulation. The
      intent of this research was to examine the patterns, attitudes, and beliefs
      regarding cigarillo use and co-use of cigarillos and cigarettes among Canadian
      young adults. METHODS: Canadians aged 19-29 years from the Greater Toronto Area,
      Ontario and Edmonton, Alberta were recruited from September 2009 to February 2010
      and in June 2010, respectively (n=133). Eligible participants completed
      questionnaires assessing cigarillo, cigarette, and cannabis use; social influence
      of usage; and beliefs about cigarillo use. RESULTS: Cigarillo use was common in
      social settings, with friends, and during leisure time. The majority of
      participants were co-users of cigarillos and cigarettes (82%), and currently used
      cannabis (72%). Respondents reported "replacing cigarette smoking" and "flavour"
      as main reasons for smoking cigarillos; and half (52%) believed they were not at
      all addicted to cigarillos. Disconcertingly, participants perceived the risk of
      cancer attributed to smoking cigarillos as significantly less than the risk of
      cancer attributed to smoking cigarettes (p<0.0001). CONCLUSION: These findings
      highlight the social nature of cigarillo use, and suggest a lack of awareness of
      the health risks associated with cigarillo and polytobacco use in this small
      convenience sample of Canadian young adults. Population-level analyses are needed
      to further investigate cigarillo, polytobacco and concurrent cannabis use
      patterns and beliefs among Canadian young adults.

PMID- 24735691
TI  - Associations between family eating behaviours and body composition measures in
      peri-adolescents: results from a community-based study of school-aged children.
AB  - OBJECTIVES: To identify key eating behaviours in children and their parents and
      to determine the associations between these behaviours and measures of body
      composition in children. METHODS: Data were collected on a sample of 431 peri
      adolescent children (12.4+/-0.3 years) and their parents from the Niagara Region.
      Body composition was assessed by trained research assistants. Eating behaviours
      were assessed using a revised version of the Family Eating and Activity Habits
      Questionnaire. Principal component analyses were used to identify key eating
      behaviours among children, mothers and fathers. Linear regression models were
      used to assess their associations with body mass index (BMI), waist-to-height
      ratio, waist-to-hip ratio, waist girth, and hip girth measures in children.
      RESULTS: Emotional/uncontrolled eating and eating by the television in children
      and their mothers were positively associated with measures of body composition in
      children. Other eating behaviours that were associated with larger measures of
      body composition in children included low frequency of eating meals with parents,
      frequent sweet beverage consumption and snacking and eating "on-the-go" in
      children, eating "on-the-go" in mothers, and emotional eating and eating by the
      television/late at night in fathers. CONCLUSIONS: The eating behaviours of
      children and mothers, and to a lesser degree fathers, are important predictors of
      children's body composition. Public health interventions designed to help mothers
      and children reduce the frequency of emotional/uncontrolled eating and eating by
      the television may be effective means of facilitating positive weight outcomes in
      children.

PMID- 24735692
TI  - Active play: an important physical activity strategy in the fight against
      childhood obesity.
AB  - OBJECTIVES: To quantify and compare the number of calories that school-aged
      Canadian children expend to meet established benchmarks for active play and
      organized physical activities (i.e., organized sport, physical education, active
      transportation). METHODS: This study was informed by the benchmarks (i.e., amount
      of activity a child needs to be sufficiently active) and grades (i.e., how Canada
      as a country is doing) for the physical activity domains included in the Active
      Healthy Kids Canada Report Card on Physical Activity for Children and Youth.
      Established physical activity energy expenditure data were used to calculate the
      number of calories that the average 6-11 year old child would expend to meet the
      Report Card physical activity benchmarks. The increase in energy expenditure at
      the population-level that would occur if each Report Card grade was to improve by
      one letter grade was estimated based on the aforementioned estimates and the
      proportion of the population impacted should the grade improve. RESULTS: When
      averaged across all 365 days of the year, the average 6-11 year old Canadian
      would expend an added 186 kcal/day to meet the active play benchmark, 23 kcal/day
      to meet the organized sport benchmark, 6 kcal/day to meet the physical education
      benchmark, and 16 kcal/day to meet the active transportation to school benchmark.
      Increasing the Report Card grades for these four domains would address 37%, 1%,
      1%, and 3% of the energy gap, respectively. CONCLUSION: Initiatives aimed at
      increasing physical activity in an attempt to address childhood obesity should
      include an active play component.

PMID- 24735693
TI  - [Children and adolescents from elsewhere: the violence experienced in their host
      society and the effects on their health, a literature].
AB  - OBJECTIVE: This integrative literature review aims to present a comprehensive
      portrayal of social violence experienced by first-generation immigrant children
      and adolescents, and its effects on their health and well-being. METHOD: A French
      and English languages literature search was conducted in eight databases, without
      restrictions on dates of publication. Thirty studies were selected. Results were
      summarized according to three aspects: 1) types of violence experienced by young
      immigrants; 2) conditions under which this violence occurs; 3) effects of such
      violence on the health and well-being of young immigrants. SYNTHESIS: Immigrant
      children and adolescents can experience various forms of physical, verbal, and
      relational violence. This violence seems to be mostly instigated by their peers
      and it has mainly been studied in terms of discrimination. Victimization may vary
      depending on factors such as ethnic composition of schools or time of residence
      in the host society. Violence may have many effects on mental health of immigrant
      youth: it is associated with both increased psychopathological symptoms and
      poorer mental health. Finally, the experience of violence is related to a more
      negative attitude of young immigrants toward their host society and a more
      positive attitude toward their own cultural community. CONCLUSION: In addition to
      its having numerous adverse effects on their mental and social health and well
      being, violence may prove to be a key factor in the experience of marginalization
      of immigrant youth. We propose certain research avenues to explore.

PMID- 24735694
TI  - Fathers' integration in Quebec's perinatal and early childhood public policies.
AB  - Mothers' physical and mental health, as well as their socio-economic status, are
      currently acknowledged as determining factors in the health and development of
      young children in Quebec. It is thus not surprising to find that the majority of
      government perinatal and early childhood initiatives are directed toward mothers.
      Yet, fathers today are increasingly involved in the care and education of their
      children, and scientific studies have shown that their involvement is just as
      crucial as that of mothers. It is recognized that a father's involvement
      optimizes the physical, cognitive, affective and social development of his
      children. The purpose of this text is to examine how fathers are taken into
      account in two public perinatal and early childhood policies. It has been found
      that fathers are virtually absent from Quebec government's objectives and
      orientations, and when they do appear, no concrete means are offered to reach
      them. Considering that health care workers have difficulty offering truly
      inclusive services to fathers, recommendations with regard to inclusion of
      fathers in public policies are necessary in order to optimize the health of
      children and their families. 

PMID- 24735695
TI  - Geographic variation in radon and associated lung cancer risk in Canada.
AB  - OBJECTIVE: Radon is an important risk factor for lung cancer. Here we use maps of
      the geographic variation in radon to estimate the lung cancer risk associated
      with living in high radon areas of Canada. METHODS: Geographic variation in radon
      was estimated using two mapping methods. The first used a Health Canada survey of
      14,000 residential radon measurements aggregated to health regions, and the
      second, radon risk areas previously estimated from geology, sediment geochemistry
      and aerial gamma-ray spectrometry. Lung cancer risk associated with living in
      these radon areas was examined using a population-based case-control study of
      2,390 lung cancer cases and 3,507 controls collected from 1994-1997 in eight
      Canadian provinces. Residential histories over a 20-year period were used in
      combination with the two mapping methods to estimate ecological radon exposures.
      Hierarchical logistic regression analyses were used to estimate odds ratios for
      lung cancer incidence, after adjusting for a comprehensive set of individual and
      geographic covariates. RESULTS: Across health regions in Canada, significant
      variation in average residential radon concentrations (range: 16-386 Bq/m3) and
      in high geological-based radon areas (range: 0-100%) is present. In multivariate
      models, a 50 Bq/m3 increase in average health region radon was associated with a
      7% (95% CI: -6-21%) increase in the odds of lung cancer. For every 10 years that
      individuals lived in high radon geological areas, the odds of lung cancer
      increased by 11% (95% CI: 1-23%). CONCLUSIONS: These findings provide further
      evidence that radon is an important risk factor for lung cancer and that risks
      are unevenly distributed across Canada.

PMID- 24735696
TI  - The relationship between awareness and supplementation: which Canadian women know
      about folic acid and how does that translate into use?
AB  - OBJECTIVE: Although the benefit of folic acid (FA) to prevent neural tube defects
      (NTD) is well established, not all women take supplements in the periconceptional
      period. This study used data from the Public Health Agency of Canada's Maternity
      Experiences Survey to evaluate determinants of awareness of FA among recently
      pregnant women in Canada, and the extent to which that translated into actual
      supplement usage. METHODS: Telephone interviews took place between October 23,
      2006 and January 31, 2007 with women who were 5 to 14 months postpartum to survey
      their experiences during pregnancy, birth and the postpartum period. These
      analyses were conducted on women who responded to questions relating to FA
      supplementation. The 6,421 respondents were weighted to represent 76,508 women
      using weights which corresponded to the sampling strata, the mother's first
      language and Aboriginal status. RESULTS: Overall, 77.6% of surveyed women knew
      that taking FA periconceptionally could help protect against NTD. Women who were
      younger, single or separated reported less awareness and use of FA, while higher
      maternal age, level of education and income were positively associated with both
      knowledge and use. Despite longstanding national guidelines for supplementation,
      there were regional variations in knowledge and use of FA. CONCLUSION: The data
      indicate clear socio-demographic differences among Canadian women with respect to
      their knowledge and use of FA. Although most women understood the benefits of FA
      supplementation, a little over a third of them did not take FA supplements prior
      to becoming pregnant, and less than half supplemented according to national
      guidelines. Identification of those subpopulations whose use of supplements is
      suboptimal may allow for targeted educational or other interventions to further
      encourage FA use.

PMID- 24735697
TI  - Factors responsible for mother-to-child HIV transmission in Ontario, Canada, 1996
      2008.
AB  - OBJECTIVE: Despite a high uptake of HIV screening and anti-retroviral prophylaxis
      in Ontario, several cases of mother-to-child (MTC) transmission occur every year.
      We wished to examine the modifiable factors responsible for MTC HIV transmission
      in Ontario, in particular HIV testing, antiretroviral prophylaxis and breast
      feeding. METHODS: Using the Ontario data from the Canadian Perinatal HIV
      Surveillance Program, we examined potential correlates of late maternal HIV
      diagnosis (i.e., diagnosed at or after delivery) among women delivering from 1996
      to 2008. To better understand the factors responsible for MTC HIV transmission,
      we reviewed the medical charts of 35 HIV-infected infants born in Ontario.
      RESULTS: Among the 645 HIV-infected mothers, 85 (13.2%) had late HIV diagnosis.
      The proportion with late HIV diagnosis significantly decreased during the study
      period, but did not differ by race/ethnicity group or maternal exposure category.
      With respect to the mothers of the 35 HIV-infected infants, 27 (77%) were
      diagnosed with HIV at or after delivery. The reasons no prenatal HIV test was
      performed were: not offered, offered but refused, no prenatal care, denied HIV
      testing history, and offered but not done. Reasons for no or incomplete
      antiretroviral  prophylaxis (ARP) among eight mothers diagnosed prior to or
      during pregnancy were: refused or non-compliant with ARP, and failed to inform
      care provider of HIV status. CONCLUSIONS: Despite the recommendation for
      universal prenatal HIV counseling and voluntary testing adopted in Ontario, MTC
      transmission continued to occur, mostly due to late HIV diagnosis of the mother.
      Future work to reduce perinatal HIV infection should focus on enhancing timely
      HIV testing of pregnant women.

PMID- 24735698
TI  - A systematic review of HIV testing among Canadian populations.
AB  - OBJECTIVE: Regular HIV testing and early detection leads to timely treatment.
      Appropriate treatment and care can prevent disease progression in the individual
      and prevent onwards transmission within the community. This review describes HIV
      testing coverage in populations disproportionately affected by HIV and in the
      general population in Canada. METHODS: A search of published and grey literature
      on HIV testing uptake in Canada was conducted. Studies reporting quantitative
      data on testing practices (ever tested, recent testing, and regular testing),
      published in either English or French from 2008-2012, were included. Studies that
      involved testing for immigration or prenatal purposes, and post-intervention
      studies, were excluded. Included studies were assessed using a modified version
      of the Public Health Agency of Canada's Descriptive Study Critical Appraisal
      Tool. Pooled prevalence for percent ever tested was calculated for subpopulations
      and heterogeneity was estimated using the I2 statistic. SYNTHESIS: A total of 26
      studies were included in the review. The highest rates of ever having been tested
      were among people who inject drugs (90.6%) and inmates (90.4%); followed by men
      who have sex with men (83.0%); Aboriginal peoples (55.5%); and the general
      population (32.8%). Limited information was available on regular and recent
      testing. CONCLUSION: HIV testing can reduce the number of undiagnosed cases in
      Canada. Future research should focus on testing coverage in certain populations,
      and on the extent to which populations engage in regular testing.

PMID- 24735699
TI  - Time since last negative HIV test among men who have sex with men and people who
      use injection drugs in British Columbia, 2006-2011.
AB  - OBJECTIVES: Canadian surveys of men who have sex with men (MSM) and people using
      injection drugs (IDU) demonstrate that most have tested for HIV at least once,
      but that half or fewer have done so in the previous year. To better inform
      targeted HIV testing guidelines for these populations, we derived estimates of
      inter-test interval (ITI) for persons newly diagnosed with HIV in British
      Columbia (BC) between 2006 and 2011, and assessed variables associated with
      longer ITI among MSM and IDU. METHODS: Provincial HIV case report and testing
      data were linked by deterministic and probabilistic matching (based on unique
      personal health number, name, and date of birth). ITI was defined as time from
      last recorded negative to first positive HIV result; those with ITI <=30 days
      were excluded. RESULTS: Of 2,004 eligible individuals, 1,116 (55.7%) had a
      recorded negative HIV test result in the previous ten years. Overall median ITI
      was 20 months with a skewed distribution (inter-quartile range 8-46); median ITI
      was 15 months for MSM and 21 months for IDU with 41.2% and 33.1% testing in the
      past year, respectively. Longer ITI was associated with older age for both
      groups, and among MSM with residence outside Vancouver and not known to have an
      HIV-positive partner. CONCLUSIONS: These findings highlight potential missed
      opportunities for earlier detection of HIV and prevention of secondary
      transmission among newly diagnosed MSM and IDU, and provide evidence to inform
      recommendations for HIV test frequency and testing strategies for these
      populations in BC.

PMID- 24735700
TI  - The economic benefits of risk factor reduction in Canada: tobacco smoking, excess
      weight and physical inactivity.
AB  - OBJECTIVE: Tobacco smoking, excess weight and physical inactivity contribute
      substantially to the preventable disease burden in Canada. The purpose of this
      paper is to apply a recently developed approach in addressing the issue of double
      counting in estimating the combined current economic burden of these risk factors
      (RFs) and to estimate the economic benefits of long-term RF reduction in Canada.
      METHODS: We used an approach based on population attributable fractions (PAF) to
      estimate the economic burden associated with the various RFs. Sex-specific
      relative risk and age-/sex-specific prevalence data were used in the modelling
      when available. Excess weight was modelled as a trichotomous exposure (normal
      weight, overweight, obese) while tobacco smoking was modelled as a tetrachotomous
      exposure (non-smoker, light, medium or heavy smoker). All costs are given in
      constant 2012 Canadian dollars. RESULTS: The annual economic burden of the RFs of
      tobacco smoking, excess weight and physical inactivity in Canada are estimated at
      $50.3 billion in 2012. Sensitivity analysis suggests a range for the economic
      burden of $41.6 to $58.7 billion. Of the $50.3 billion, $21.3 ($20.0 to $22.6)
      billion is attributable to tobacco smoking, $19.0 ($13.8 to $24.0) billion to
      excess weight and $10.0 ($7.8 to $12.0) billion to physical inactivity. A 1%
      relative annual reduction in each of the three RFs would result in an $8.5
      billion annual reduction in economic burden by 2031. CONCLUSION: A modest annual
      1% relative reduction in the RFs of tobacco smoking, excess weight and physical
      inactivity can have a substantial health and economic impact over time at the
      population level.

PMID- 24735701
TI  - Prevalence, incidence, awareness and control of hypertension in the province of
      Quebec: perspective from administrative and survey data.
AB  - OBJECTIVES: Hypertension is a major risk factor for cardiovascular diseases.
      Nearly one adult in four was diagnosed with hypertension in 2007-2008 in Canada.
      One of the objectives of this study was to determine whether the prevalence of
      hypertension in Quebec as assessed using administrative data is comparable to
      that specifically measured, especially for the elderly population. METHODS:
      Trends in prevalence, incidence and mortality were examined using the Quebec
      Integrated Chronic Disease Surveillance System built from grouping numerous
      administrative databases from 1996-1997 to 2009-2010. Blood pressure
      measurements, hypertension prevalence, awareness and control were obtained in
      1,706 Quebecers in the combined cycles of the Canadian Health Measures Survey.
      RESULTS: Using administrative databases, 23.6% [95% confidence interval, 23.5
      23.6] of the Quebec population (n=1,433,400) aged >=20 years was diagnosed with
      hypertension in 2009-2010, an increase of 32.1% compared to 2000 2001. The
      incidence decreased by 27.3%. Among people aged >=65 years, the prevalence rose
      to 69.0% [95% CI: 68.8 69.2] in women and 61.7% [95% CI: 61.5-61.9] in men. For
      people aged 20-79 years, the prevalence of hypertension was lower with the
      administrative data compared to the survey (20.2% and 23.1%, respectively). The
      level of awareness, treatment and control were 84.3%, 83.1% and 67.9%,
      respectively. CONCLUSION: The prevalence of hypertension derived from
      administrative data is comparable to that obtained with a health measured survey.
      Elderly women (>=65 years) are a very high-risk subgroup. The levels of
      awareness, treatment and control of hypertension in Quebec are very high.

PMID- 24735702
TI  - Defining research priorities for bacterial sexually transmitted infections in
      Canada.
AB  - OBJECTIVES: We aimed to define priority areas for research on chlamydia,
      gonorrhea, and syphilis in Canada through the use of a consensus method. METHODS:
      A modified Delphi method was conducted, consisting of two online surveys and an
      in-person meeting. Participants included people working in bacterial sexually
      transmitted infections (STIs) across Canada, including clinicians, policy-makers,
      public health practitioners, and researchers. RESULTS: Consensus was achieved
      regarding the most important priority topics in bacterial STI research in Canada,
      within five general priority areas: the epidemiology of bacterial STIs,
      screening, partner notification and contact tracing, antimicrobial resistance,
      and identification of best practices for the prevention and control of bacterial
      STIs. CONCLUSIONS: The findings of this consensus process can be used to inform
      research efforts, which could contribute to more effective control of bacterial
      STIs in Canada.

PMID- 24735703
TI  - Research on genetically modified foods: double standards of transparency.

PMID- 24735704
TI  - Increased collision risk among drivers who report driving after using alcohol and
      after using cannabis.

PMID- 24735705
TI  - Distribution and dynamics of mangrove forests of South Asia.
AB  - Mangrove forests in South Asia occur along the tidal sea edge of Bangladesh,
      India, Pakistan, and Sri Lanka. These forests provide important ecosystem goods
      and services to the region's dense coastal populations and support important
      functions of the biosphere. Mangroves are under threat from both natural and
      anthropogenic stressors; however the current status and dynamics of the region's
      mangroves are poorly understood. We mapped the current extent of mangrove forests
      in South Asia and identified mangrove forest cover change (gain and loss) from
      2000 to 2012 using Landsat satellite data. We also conducted three case studies
      in Indus Delta (Pakistan), Goa (India), and Sundarbans (Bangladesh and India) to
      identify rates, patterns, and causes of change in greater spatial and thematic
      details compared to regional assessment of mangrove forests. Our findings
      revealed that the areal extent of mangrove forests in South Asia is approximately
      1,187,476 ha representing ~7% of the global total. Our results showed that from
      2000 to 2012, 92,135 ha of mangroves were deforested and 80,461 ha were
      reforested with a net loss of 11,673 ha. In all three case studies, mangrove
      areas have remained the same or increased slightly, however, the turnover was
      greater than the net change. Both, natural and anthropogenic factors are
      responsible for the change and turnover. The major causes of forest cover change
      are similar throughout the region; however, specific factors may be dominant in
      specific areas. Major causes of deforestation in South Asia include (i)
      conversion to other land use (e.g. conversion to agriculture, shrimp farms,
      development, and human settlement), (ii) over-harvesting (e.g. grazing, browsing
      and lopping, and fishing), (iii) pollution, (iv) decline in freshwater
      availability, (v) floodings, (vi) reduction of silt deposition, (vii) coastal
      erosion, and (viii) disturbances from tropical cyclones and tsunamis. Our
      analysis in the region's diverse socio-economic and environmental conditions
      highlights complex patterns of mangrove distribution and change. Results from
      this study provide important insight to the conservation and management of the
      important and threatened South Asian mangrove ecosystem. 

PMID- 24735706
TI  - A rule-based ontological framework for the classification of molecules.
AB  - BACKGROUND: A variety of key activities within life sciences research involves
      integrating and intelligently managing large amounts of biochemical information.
      Semantic technologies provide an intuitive way to organise and sift through these
      rapidly growing datasets via the design and maintenance of ontology-supported
      knowledge bases. To this end, OWL-a W3C standard declarative language- has been
      extensively used in the deployment of biochemical ontologies that can be
      conveniently organised using the classification facilities of OWL-based tools.
      One of the most established ontologies for the chemical domain is ChEBI, an open
      access dictionary of molecular entities that supplies high quality annotation and
      taxonomical information for biologically relevant compounds. However, ChEBI is
      being manually expanded which hinders its potential to grow due to the limited
      availability of human resources. RESULTS: In this work, we describe a prototype
      that performs automatic classification of chemical compounds. The software we
      present implements a sound and complete reasoning procedure of a formalism that
      extends datalog and builds upon an off-the-shelf deductive database system. We
      capture a wide range of chemical classes that are not expressible with OWL-based
      formalisms such as cyclic molecules, saturated molecules and alkanes.
      Furthermore, we describe a surface 'less-logician-like' syntax that allows
      application experts to create ontological descriptions of complex biochemical
      objects without prior knowledge of logic. In terms of performance, a noticeable
      improvement is observed in comparison with previous approaches. Our evaluation
      has discovered subsumptions that are missing from the manually curated ChEBI
      ontology as well as discrepancies with respect to existing subclass relations. We
      illustrate thus the potential of an ontology language suitable for the life
      sciences domain that exhibits a favourable balance between expressive power and
      practical feasibility. CONCLUSIONS: Our proposed methodology can form the basis
      of an ontology-mediated application to assist biocurators in the production of
      complete and error-free taxonomies. Moreover, such a tool could contribute to a
      more rapid development of the ChEBI ontology and to the efforts of the ChEBI team
      to make annotated chemical datasets available to the public. From a modelling
      point of view, our approach could stimulate the adoption of a different and
      expressive reasoning paradigm based on rules for which state-of-the-art and
      highly optimised reasoners are available; it could thus pave the way for the
      representation of a broader spectrum of life sciences and biomedical knowledge.

PMID- 24735707
TI  - Motivational interviewing with American Indian mothers to prevent early childhood
      caries: study design and methodology of a randomized control trial.
AB  - BACKGROUND: This randomized control trial assesses the effectiveness of
      motivational interviewing (MI) to encourage behavior change in new mothers
      relating to caries prevention when caring for their newborn American Indian (AI)
      infants and young AI children. METHODS/DESIGN: The study is a randomized control
      trial. We hypothesize that when motivational interviewing is added to enhanced
      community oral health education services, the new mothers will achieve greater
      reduction of caries experience in their AI children compared to those who are
      receiving enhanced community services (ECS) alone. Six hundred mothers or
      caregivers of AI newborns will be enrolled into the study and randomized to one
      of the two intervention groups over a two-year period. The children will be
      followed until the child's third birthday. A cost analysis of the study is being
      conducted in tandem with the enhanced community services, motivational
      interviewing behavioral interventions, and the dental screenings for the length
      of the study. DISCUSSION: The trial is now in the implementation phase and a
      number of threats to successful completion, such as recruitment and retention
      challenges in a vast, rural geographic area, have been addressed. The protocol
      provides a unique model for oral health interventions using principles of
      community-based participatory research and is currently on schedule to meet study
      objectives. If the study is successful, motivational interviewing intervention
      can be applied in AI communities to reduce ECC disparities in this disadvantaged
      population, with study of further applicability in other populations and
      settings. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01116726.

PMID- 24735708
TI  - Characterization, mechanism of anticoagulant action, and assessment of
      therapeutic potential of a fibrinolytic serine protease (Brevithrombolase)
      purified from Brevibacillus brevis strain FF02B.
AB  - In this study, biochemical and pharmacological characterization of
      Brevithrombolase, a fibrinolytic serine protease purified from Brevibacillus
      brevis strain FF02B has been reported. An assessment of its thrombolytic potency
      has also been made. The molecular mass of this monomeric protease was determined
      as 55 kDa, and 56043 Da, respectively, by SDS-PAGE and MALDI-TOF-MS. In the
      analytical studies, the N-terminal sequence of Brevithrombolase was found to be
      blocked; however, the peptide mass fingerprinting and amino acid composition
      analyses demonstrated the similarity of Brevithrombolase with endopeptidases in
      possessing serine in their catalytic triad. This finding was confirmed by the
      observation that the serine protease inhibitors decrease the catalytic
      (fibrinolytic) activity of Brevithrombolase. The secondary structure of
      Brevithrombolase was composed of 30.6% alpha helix and 69.4% random coil.
      Brevithrombolase showed the Km and Vmax values towards the chromogenic substrate
      for plasmin at 0.39 mM and 14.3 MUmol/min, respectively. Brevithrombolase
      demonstrated optimum fibrinolytic activity at pH 7.4 and 37  degrees C, and
      showed marginal hydrolytic activity towards globulin, casein and fibrinogen. The
      anticoagulant potency of Brevithrombolase was comparable to the low molecular
      mass heparin/antithrombin-III and warfarin. Among the three enzymes
      Brevithrombolase, plasmin and streptokinase-the fibrinolytic activity and in
      vitro thrombolytic potency of Brevithrombolase was found to be superior. The RP
      HPLC and SDS-PAGE analyses suggested a similar pattern of fibrin degradation by
      Brevithrombolase and plasmin, indicating that former enzyme is a plasmin-like
      fibrinolytic serine protease. Brevithrombolase did not show in vitro cytotoxicity
      on HT29 and HeLa cells or hemolytic activity. At a dose of 10 mg/kg,
      Brevithrombolase did not exhibit lethality or toxicity on Wistar strain albino
      rats. Brevithrombolase did not inhibit factor Xa, and its mechanism of
      anticoagulant action was associated with the enzymatic cleavage of thrombin. The
      combined properties of Brevithrombolase indicate its therapeutic potential in
      peptide-based cardiovascular drug development.

PMID- 24735709
TI  - SGLT2 inhibitors in the treatment of type 2 diabetes.
AB  - The kidney plays an important role in glucose homeostasis via its production,
      utilization, and, most importantly, reabsorption of glucose from glomerular
      filtrate which is largely mediated via the sodium glucose co-transporter 2
      (SGLT2). Pharmacological inhibition of SGLT2 increases urinary glucose excretion
      and decreases plasma glucose levels in an insulin-independent manner. Agents that
      inhibit SGLT2 represent a novel class of drugs, which has recently become
      available for treatment of type 2 diabetes. This article summarizes the rationale
      for use of these agents and reviews available clinical data on their efficacy,
      safety, and risks/benefits. 

PMID- 24735710
TI  - Residual dysglycemia when at target HbA(1c) of 7% (53mmol/mol) in persons with
      type 2 diabetes.
AB  - AIMS: To understand the composition of the residual dysglycemia when HbA1c is
      between 6.5% (48mmol/mol) and 7% (53mmol/mol), representing the definition of
      diabetes and the recommended treatment goal, respectively. METHODS: One hundred
      persons with type 2 diabetes and a HbA1c<7% (53mmol/mol), treated with diet alone
      and/or oral hypoglycemic agents underwent continuous glucose monitoring (CGM) and
      were further divided into two subgroups 1 (n=50) and 2 (n=50) according to
      whether the HbA1c was <6.5% (48mmol/mol) or 6.5-6.9% (48-52mmol/mol),
      respectively. A similar analysis was performed in those on diet alone: subgroups
      A (n=34, HbA1c<6.5%, 48mmol/mol) and B (n=10, HbA1c 6.5-6.9%, 48-52mmol/mol). The
      residual dysglycemia determined from the CGM was assessed using glucose exposures
      defined as areas under curves (AUCs) and mean glucose values. RESULTS: Averaged 2
      h postprandial glucose value (averaged PPG, mmol/L, mean+/-SD) and postprandial
      glucose exposure (AUCpp, mean+/-SD, mmol.L(-1).h) were significantly higher in
      subgroup 2 (mean HbA1c=6.7%, 50mmol/mol) than in subgroup 1 (mean HbA1c=6.0%,
      42mmol/mol): averaged PPG=8.1+/-1.3 versus 7.3+/-1.3mmol/L (p<0.002);
      AUCpp=23.5+/-8.6 versus 16.2+/-8.6 (p<0.0001). The percentages of persons with
      averaged PPG>=7.8mmol/L were 52% and 24% (p<0.01) in subgroups 2 and 1,
      respectively. Similar results were observed in those (subgroups A and B) who were
      on diet alone. CONCLUSIONS: The residual dysglycemia in type 2 diabetes with
      HbA1c between 6.5 and 6.9% (48-52mmol/mol) inclusive is mainly due to remnant
      abnormal postprandial glucose excursions. Consequently, HbA1c<6.5% (48mmol/mol)
      is an achievable goal with therapeutic measures aimed at reducing postmeal
      glucose when the HbA1c is at 7% (53mmol/mol).

PMID- 24735711
TI  - C-terminal tensin-like (CTEN): a promising biomarker and target for cancer.
AB  - C-terminal tensin-like (cten, also known as tensin4, TNS4) is a member of the
      tensin family. Cten protein, like the other three tensin family members,
      localizes to focal adhesion sites but only shares sequence homology with other
      tensins at its C-terminal region, which contains the SH2 and PTB domains. Cten is
      abundantly expressed in normal prostate and placenta and is down-regulated in
      prostate cancer. However, overexpression of cten frequently associates with
      tumors derived from breast, colon, lung, stomach, skin and pancreas. A variety of
      cancer-associated growth factors and cytokines induce cten expression. Up
      regulated cten promotes cell motility, prolongs epidermal growth factor receptor
      signaling, and enhances tumorigenicity. Emerging findings suggest that cten is a
      promising biomarker and therapeutic target for various cancers. 

PMID- 24735712
TI  - Molecular modelling approaches for cystic fibrosis transmembrane conductance
      regulator studies.
AB  - Cystic fibrosis (CF) is one of the most common genetic disorders, caused by loss
      of function mutations in the gene encoding the CF transmembrane conductance
      regulator (CFTR) protein. CFTR is a member of ATP-binding cassette (ABC)
      transporters superfamily and functions as an ATP-gated anion channel. This review
      summarises the vast majority of the efforts which utilised molecular modelling
      approaches to gain insight into the various aspects of CFTR protein, related to
      its structure, dynamic properties, function and interactions with other protein
      partners, or drug-like compounds, with emphasis to its relation to CF disease.

PMID- 24735713
TI  - Cystic fibrosis, a multi-systemic mucosal disease: 25 years after the discovery
      of CFTR.

PMID- 24735714
TI  - Clinical utility of magnetic resonance imaging in the follow-up of chronic aortic
      type B dissection.
AB  - Several imaging modalities are utilised in the assessment of disease progression
      in chronic aortic dissection. We present the case of a 66 year-old male who
      underwent ascending aorta repair for Stanford type A aortic dissection. On follow
      up the persisting dissection of the descending thoracic aorta was observed to
      regress on magnetic resonance imaging (MRI). MRI has several advantages over
      computed tomography (CT) scanning and echocardiography in the follow-up phase of
      this disease. 

PMID- 24735715
TI  - Indian paediatricians to be trained in managing childhood TB.

PMID- 24735718
TI  - Psychometric properties and measurement invariance of the Spanish version of the
      11-item De Jong Gierveld loneliness scale.
AB  - ABSTRACT Background: Loneliness has been associated with physical and mental
      health problems. It has also been considered a serious social problem that
      increases the use and costs of health services. The most widely used instrument
      in Europe for measuring loneliness is the de Jong Gierveld Loneliness Scale
      (DJGLS). The aim of this study was to examine the psychometric properties of the
      11-item DJGLS by means of the Rasch model, and its convergent and discriminant
      validity. Methods: Participants were a representative sample of Spanish community
      dwelling adults aged 60 and older. We evaluated sociodemographic variables,
      health, social support, social activity, and subjective well-being measures.
      Results: Person and item fit statistics, and standardized residual principal
      component analysis revealed that the DJGLS was essentially unidimensional.
      However, we found DIF across marital status and living arrangements. Moderate to
      high associations were found between loneliness and depression, self-rated
      loneliness, positive and negative emotions, and satisfaction with life. The DJGLS
      differentiated between well known-groups according to gender, marital status,
      living arrangements, health, structural and functional aspects of social
      networks, and social activity. Conclusions: The DJGLS is a valid and reliable
      instrument for measuring loneliness in Spanish older adults. The addition of a
      few items in order to improve the measurement range is strongly recommended. Our
      findings are consistent with previous research indicating that loneliness is an
      important aspect of mental health and subjective well-being, and support the use
      of the scale to detect vulnerable population in old age.

PMID- 24735717
TI  - Subtotal glossectomy preserving half the tongue base prevents taste disorder in
      patients with tongue cancer.
AB  - Most patients diagnosed with tongue carcinoma undergo surgical resection and
      reconstructive surgery to preserve tongue mobility and swallowing functions.
      Twenty-four patients who underwent a total or subtotal glossectomy and surgical
      reconstruction were evaluated for residual taste sensation. The graded filter
      paper test for all four tastes (sweet, salt, sour, and bitter) was performed on
      the posterior wall of the oropharynx and on tongue remnants if they were visible
      from the mouth. Eleven of the 24 patients were aware of their taste disorder
      after surgery. Four patients with more than 1/2 residual tongue base had no taste
      complaints, whereas seven of 14 patients with less than 1/3 residual tongue base
      reported taste abnormalities. Patients who could only tolerate a poor diet or
      tube feeding tended to have taste complaints (P=0.017). The taste test showed
      that the taste threshold of the residual tongue was significantly lower compared
      to controls. The taste threshold was significantly correlated with the remaining
      volume of tongue base. Patients with >1/2 the tongue base remaining had good
      taste sensation, whereas those with <1/3 residual tissue had impaired taste. This
      study suggests that glossectomy strategies aimed at preserving at least half the
      tongue base may substantially reduce dysgeusia in the patients. 

PMID- 24735716
TI  - Distinguishing classical papillary thyroid microcancers from follicular-variant
      microcancers.
AB  - BACKGROUND: Papillary thyroid microcarcinomas (mPTCs), tumors less than or equal
      to 1 cm, have been considered the same clinical entity as microfollicular-variant
      papillary thyroid microcarcinomas (mFVPTCs). The purpose of this study was to use
      population-level data to characterize differences between mFVPTC and mPTC.
      MATERIALS AND METHODS: We identified adult patients diagnosed with mFVPTC or mPTC
      between 1998 and 2010 in the Surveillance, Epidemiology, and End Results
      database. Binary comparisons were made with the Student t-test and chi-squared
      test. Multivariate logistic regression was used to further analyze lymph node
      metastases and multifocality. RESULTS: Of the 30,926 cases, 8697 (28.1%) were
      mFVPTC. Multifocal tumors occurred with greater frequency in the mFVPTC group
      compared with the mPTC group (35.4% versus 31.7%; P<0.01). Multivariate logistic
      regression indicated that patients with mFVPTC had a 26% increased risk of
      multifocality (odds ratio, 1.26; 95% confidence interval, 1.2-1.4; P<0.01). In
      contrast, lymph node metastases were nearly twice as common in the mPTC group
      compared with the mFVPTC group (6.8% versus 3.6%; P<0.01). Multivariate logistic
      regression confirmed that patients with mPTC had a 69% increased risk of lymph
      node metastases compared with patients with mFVPTC (odds ratio, 1.69; 95%
      confidence interval, 1.4-2.0; P<0.01). CONCLUSIONS: Multifocality is not unique
      to classical mPTC and occurs more often in mFVPTC. The risk of lymph node
      metastases is greater for mPTC than mFVPTC. The surgeon should be aware of these
      features as they may influence the treatment for these microcarcinomas.

PMID- 24735719
TI  - The relationship between neuroticism and inflammatory markers: a twin study.
AB  - INTRODUCTION: Neuroticism is an important marker of vulnerability for both mental
      and physical disorders. Its link with multiple etiological pathways has been
      studied before. Inflammatory markers have been demonstrated to predict similar
      mental and physical disorders as neuroticism. However, currently no study has
      focused on the shared genetic background of neuroticism and inflammatory markers.
      In the present study we will focus on the phenotypic and genetic relationship
      between neuroticism and three commonly used inflammatory markers: C-reactive
      protein (CRP), fibrinogen and Immunoglobulin-G (IgG). MATERIAL AND METHODS: The
      study was conducted in 125 Dutch female twin pairs. For each participant, four
      different neuroticism scores were available to calculate a neuroticism composite
      score that was used in the statistical analyses. Blood samples for inflammatory
      marker determination were taken after an overnight fast. Heritabilities,
      phenotypic and genetic correlations were estimated using bivariate structural
      equation modeling. RESULTS: Heritabilities are fair for neuroticism (0.55), CRP
      (0.52) and fibrinogen (0.67) and moderate for IgG (0.43). No significant
      phenotypic or genetic correlations were found between neuroticism and the
      inflammatory markers. Interaction models yielded no moderation of the genetic and
      environmental pathways in the regulation of inflammatory markers by neuroticism.
      CONCLUSION: Substantial heritabilities were observed for all variables. No
      evidence was found for significant shared (or moderation of) genetic or
      environmental pathways underlying neuroticism and inflammatory status.

PMID- 24735721
TI  - Payment reform and changes in health care in China.
AB  - This paper is intended to assess the primary effects on cost, utilization and
      quality of care from payment reform of capitation and open enrollment in Changde
      city, Hunan Province of China. Open enrollment policy was introduced to deal with
      possible cream skimming associated with capitation. Based on the longitudinal
      Urban Resident Basic Medical Insurance (URBMI) Household Survey, this study
      analyses the URBMI data through a set of regression models. The original data
      included over five thousand inpatient admissions during the study period between
      2008 and 2010. The study finds the payment reform to reduce its inpatient out-of
      pocket cost by 19.7%, out-of-pocket ratio by 9.5%, and length of stay by 17.7%.
      However, the total inpatient cost, drug cost ratio, treatment effect, and patient
      satisfaction showed little difference between Fee-For-Service and capitation
      models. We conclude that the payment reform in Changde did not reduce overall
      inpatient expenditure, but it decreased the financial risk and length of stay of
      inpatient patients without compromising quality of care. The findings would
      contribute to the health care payment literatures from developing countries and
      open further research tracks on the ability of open enrollment to compensate for
      capitation drawbacks.

PMID- 24735720
TI  - The effects of socioeconomic incongruity in the neighbourhood on social support,
      self-esteem and mental health in England.
AB  - Analyses of neighbourhood socioeconomic characteristics and health indicators
      consistently show that health is worse in poorer neighbourhoods. However, some
      studies that examined neighbourhood effects separately for individuals of
      different socioeconomic position found that poor people may derive health
      benefits from living in poor neighbourhoods where they are socioeconomically
      congruous. This study investigates whether such patterns may be driven by
      psychosocial factors. The sample consisted of 4871 mothers in the Millennium
      Cohort Study aged 14-53. The outcomes analysed were neighbourhood friendship,
      emotional support, self-esteem and depression or anxiety. Neighbourhood status
      was classified by residents' educational and occupational status derived from the
      2001 Census. We used multilevel logistic regression, adjusting for mothers' socio
      demographic characteristics: first analysing health by neighbourhood status
      separately for the highest and lowest status mothers, then testing for
      modification in the association between neighbourhood status and health, by
      individual status. Results show that for highest status mothers, living in mixed
      or high status neighbourhoods compared to low status neighbourhoods significantly
      reduced the odds of having no friends in the neighbourhood by 65%. Living in high
      status neighbourhoods compared to low status neighbourhoods also significantly
      reduced the odds of depression or anxiety for highest status mothers by 41%. No
      associations were found for emotional support or self-esteem amongst highest
      status mothers. No associations were found for any outcome among lowest status
      mothers. In conclusion, low status mothers in England did not have better social
      support, self-esteem, or mental health when living in low status neighbourhoods
      compared to high status neighbourhoods; any benefits of socioeconomic congruity
      may have been counteracted by neighbourhood deprivation. Nevertheless, we found
      that mothers of high status do have significantly better neighbourhood friendship
      and mental health when living in socioeconomic congruity within neighbourhoods.
      Whether these associations are causal or are another reflection of material
      advantage remains unclear. 

PMID- 24735722
TI  - Folding of outer membrane protein A in the anionic biosurfactant rhamnolipid.
AB  - Folding and stability of bacterial outer membrane proteins (OMPs) are typically
      studied in vitro using model systems such as phospholipid vesicles or surfactant.
      OMP folding requires surfactant concentrations above the critical micelle
      concentration (cmc) and usually only occurs in neutral or zwitterionic
      surfactants, but not in anionic or cationic surfactants. Various Gram-negative
      bacteria produce the anionic biosurfactant rhamnolipid. Here we show that the OMP
      OmpA can be folded in rhamnolipid at concentrations above the cmc, though the
      thermal stability is reduced compared to the non-ionic surfactant dodecyl
      maltoside. We discuss implications for possible interactions between OMPs and
      biosurfactants in vivo. 

PMID- 24735723
TI  - The flanking sequence contributes to the immobilisation of spermine at the G
      quadruplex in the NHE (nuclease hypersensitivity element) III1 of the c-Myc
      promoter.
AB  - Defining the molecular basis of the DNA sequence selectivity of polyamine binding
      is central to understanding polyamine-dependent gene expression. We have studied,
      by selective NMR experiments, the variation of spermine mobility and conformation
      in the presence of G-quadruplexes formed by sequences of the purine-rich strand
      of the c-Myc promoter, nuclease hypersensitivity element III1 (NHE III1). All the
      NHE quadruplexes restrict spermine mobility and induce a spermine conformational
      change but the most effective immobilisation occurs when all five G-tracts of the
      NHE III1 are present. This suggests structure within the nucleotides flanking the
      G-quadruplex has a role in immobilising spermine. 

PMID- 24735724
TI  - A different path: revealing the function of staphylococcal proteins in biofilm
      formation.
AB  - Staphylococcus aureus and Staphylococcus epidermidis cause dangerous and
      difficult to treat medical device-related infections through their ability to
      form biofilms. Extracellular poly-N-acetylglucosamine (PNAG) facilitates biofilm
      formation and is a vaccination target, yet details of its biosynthesis by the
      icaADBC gene products is limited. IcaC is the proposed transporter for PNAG
      export, however a comparison of the Ica proteins to homologous exo-polysaccharide
      synthases suggests that the common IcaAD protein components both synthesise and
      transport the PNAG. The limited distribution of icaC to the Staphylococcaceae and
      its membership of a family of membrane-bound acyltransferases, leads us to
      suggest that IcaC is responsible for the known O-succinylation of PNAG that
      occurs in staphylococci, identifying a potentially new therapeutic target
      specific for these bacteria. 

PMID- 24735725
TI  - A cis-encoded sRNA controls the expression of fabH2 in Yersinia.
AB  - YsrH is a novel cis-encoded sRNA located on the opposite strand to fabH2, which
      is essential for fatty acid biosynthesis in bacteria. In this study, YsrH
      mediated regulation of fabH2 expression was investigated in Yersinia
      pseudotuberculosis. Constitutive and inducible over-expression of YsrH decreased
      the mRNA level of fabH2, while expression of downstream fabD and fabG remained
      unaffected. Polynucleotide phosphorylase (PNPase) also played an important role
      in this regulation process by mediating YsrH decay in the exponential phase.
      Thus, our data defines a cis-encoded sRNA that regulates fatty acid synthesis via
      a regulatory mechanism also involving PNPase. 

PMID- 24735726
TI  - Unfolding of in planta activity of anti-rep ribozyme in presence of a RNA
      silencing suppressor.
AB  - Antisense RNA ribozymes have intrinsic endonucleolytic activity to effect
      cleavage of the target RNA. However, this activity in vivo is often controlled by
      the dominance of antisense or other double-stranded RNA mechanism. In this work,
      we demonstrate the in planta activity of a hammerhead ribozyme designed to target
      rep-mRNA of a phytopathogen Mungbean Yellow Mosaic India virus (MYMIV) as an
      antiviral agent. We also found RNA-silencing is induced on introduction of
      catalytically active as well as inactive ribozymes. Using RNA-silencing
      suppressors (RSS), we demonstrate that the endonucleolytic activity of ribozymes
      is a true phenomenon, even while a mutated version may demonstrate a similar down
      regulation of the target RNA. This helps to ease the confusion over the action
      mechanism of ribozymes in vivo. 

PMID- 24735727
TI  - Melanotic Xp11 translocation renal cancer: report of a case with a unique
      intratumoral sarcoid-like reaction.
AB  - BACKGROUND: Melanotic Xp11 translocation renal cancer is a rare tumor belonging
      to the family of microphthalmia-associated transcription factor
      (MiTF)/transcription factor E (TFE) neoplasms. This tumor family also includes
      alveolar soft part sarcoma, perivascular epithelioid cell neoplasms, Xp11
      translocation renal cell carcinoma, and melanoma. To date, six confirmed
      melanotic Xp11 translocation cancers (five renal, one ovarian) have been reported
      in the literature. CASE REPORT: Here, we report the clinical, histologic,
      immunohistochemical, and molecular features of a unique melanotic Xp11
      translocation renal cancer arising in a 34-year-old African-American female.
      Histologically, the tumor was composed of epithelioid tumor cells arranged in a
      nested pattern. The cells had clear to eosinophilic granular cytoplasm, vesicular
      nuclear chromatin, and prominent nucleoli. Multifocal intracytoplasmic deposits
      of granular brown melanin pigment were identified and confirmed by Fontana-Masson
      stain. An unusual histologic feature, not previously reported in melanotic Xp11
      translocation renal cancer, was a sarcoid-like granulomatous reaction consisting
      of tight epithelioid granulomas with lymphocytic cuffing, numerous giant cells,
      and calcifications. Nuclear transcription factor E3 expression was identified by
      immunohistochemistry and TFE3 rearrangement was confirmed by fluorescence in situ
      hybridization. Additional immunohistochemical findings included immunoreactivity
      for HMB45, cathepsin K, and progesterone receptor; negative staining was seen
      with actin, desmin, cytokeratins, epithelial membrane antigen, CD10, vimentin,
      and PAX-8. The patient is currently free of disease, two years following initial
      clinicoradiologic presentation and twenty-two months following partial
      nephrectomy without additional therapy. CONCLUSION: This report further expands
      the spectrum of morphologic and clinical findings previously described in
      melanotic Xp11 translocation renal cancer, a distinctive tumor showing
      overlapping features between Xp11 translocation renal cell carcinoma, melanoma,
      and perivascular epithelioid cell neoplasms. VIRTUAL SLIDES: The virtual slide(s)
      for this article can be found here:
      http://www.diagnosticpathology.diagnomx.eu/vs/7225796341180634.

PMID- 24735728
TI  - Re-examining outcomes after unsuccessful out-of-hospital resuscitation in the era
      of field termination of resuscitation guidelines and regionalized post
      resuscitation care.
AB  - BACKGROUND: Dismal prognosis after failed out-of-hospital resuscitation has
      previously been demonstrated. Changes in resuscitation and post-resuscitation
      care may affect patient outcomes. We describe characteristics and outcomes of
      patients with out-of-hospital cardiac arrest (OOHCA) transported to specialty
      cardiac centers after failure of out-of-hospital interventions. METHODS: In Los
      Angeles (LA) County, patients with non-traumatic OOHCA with return of spontaneous
      circulation (ROSC) are transported to specialized cardiac care centers. Outcomes
      are reported to a registry maintained by the LA County Emergency Medical Services
      (EMS) Agency. We report patient characteristics and outcomes for the subset of
      patients treated at these specialty centers in whom initial ROSC was achieved in
      the ED. The primary outcome was neurologically intact survival, defined by a
      cerebral performance category (CPC) score of 1 or 2. RESULTS: 105 patients
      transported to the SRC after failure to achieve ROSC with out-of-hospital
      resuscitation were successfully resuscitated in the ED. The median age was 68
      years (IQR 57-78); 74 (70%) were male. The presenting rhythm was ventricular
      fibrillation or ventricular tachycardia in 40 patients (38%) and 86 (82%) were
      witnessed. Twenty-two patients (21%) survived to hospital discharge. Of the 103
      patients with known CPC scores, 13 (13% [95% CI 7-21%]) survived to hospital
      discharge with a CPC score of 1 or 2. No patient who survived with good
      neurologic outcome met criteria for termination of resuscitation in the field.
      CONCLUSION: Failure of out-of-hospital resuscitation is not universally
      predictive of poor neurologic outcome.

PMID- 24735729
TI  - Health-seeking behaviour in the city of Lubumbashi, Democratic Republic of the
      Congo: results from a cross-sectional household survey.
AB  - BACKGROUND: Concerns about the occurrence of disease among household members
      generally initiate treatment-seeking actions. This study aims to identify the
      various treatment-seeking options of patients in Lubumbashi, analyze their health
      seeking behaviour, identify determinants for the use of formal care, and analyze
      direct health care expenditure. METHODS: A cross-sectional survey of households
      in Lubumbashi was conducted in July 2010. Information was collected from a
      randomly selected sample of 251 households with at least one member who had been
      ill in the 2 weeks preceding the survey. RESULTS: Frequently used initial
      treatment-seeking options consist of self-medication based on modern medicines
      (54.6%), the use of first-line health services (23.1%) and hospitals (11.9%),
      with a perceived effectiveness of 51%, 83% and 91% respectively. If people go for
      a second option, then formal health care services are most often preferred. The
      majority (60%) of patients' spontaneous itineraries reflect the expected
      functioning of a local health care system, with a patient flow characterised by
      the use of a first line health facility prior to the use of hospital-based
      services. Chronicity of the disease is the main determinant of seeking formal
      care. Analysis of care expenditure reveals that drugs are the only line of
      expenditure in the informal system and the main source of expenditure in the
      formal system; costs do not discriminate between first-line health services and
      hospitals, and the payment system is regressive since the poorest patients pay
      the same amounts as the richest. CONCLUSIONS: This study points to the importance
      of self-medication as the first therapeutic option for the majority of patients
      in Lubumbashi, whatever the nature of the health problem. There is a lot of room
      to rationalise this practice. Although formal care is not common initial
      therapeutic option, it is the source of care most patients turn to, especially
      when they believe having a chronic disease. Patients' itineraries in this urban
      environment are complex; health managers should try and deal with this reality.
      Finally, our study indicates that poor patients face the same level of out-of
      pocket payments as the more wealthy ones, hence the need for more equitable
      health care financing arrangements.

PMID- 24735730
TI  - One size does not fit all: can we choose the best sequence of treatment in
      asymptomatic castration-resistant prostate cancer patients?

PMID- 24735731
TI  - Tissue therapeutics and regenerative medicine.

PMID- 24735732
TI  - PI3K inhibitors as potential therapeutics for autoimmune disease.
AB  - Aberrant overactivation of the immune system can give rise to chronic and
      persistent self-attack, culminating in autoimmune disease. This is currently
      managed therapeutically using potent immunosuppressive and anti-inflammatory
      drugs. Class I phosphoinositide 3-kinases (PI3Ks) have been identified as ideal
      therapeutic targets for autoimmune diseases given their wide-ranging roles in
      immunological processes. Recent studies into the function of selective PI3K
      inhibitors in vitro and in vivo have yielded encouraging results, allowing
      progression into the clinic. Here, we review their recent progress across a range
      of autoimmune diseases. 

PMID- 24735733
TI  - Show me the Money: the impact of actual rewards and losses on the feedback
      negativity.
AB  - The feedback negativity (FN) is an event-related potential component which is
      typically conceptualized as a negativity in response to losses that is absent in
      response to gains. However, there is also evidence that variation in the FN
      reflects the neural response to gains. The present study sought to explore these
      possibilities by manipulating the context in which loss and gain feedback was
      presented in a straightforward gambling task. In half the blocks, participants
      could win or lose money (Value condition), and in half the blocks, participants
      could not win or lose any money (No Value condition). The degree to which losses
      and gains were differentiated from one another (i.e., the DeltaFN) was greater in
      the Value condition than in the No Value condition. Furthermore, though the
      responses to loss feedback and gain feedback were each enhanced in the Value
      condition relative to the No-Value condition, the effect of the monetary
      manipulation was substantially larger for the positivity to gains than the
      negativity to losses. This is consistent with the notion that the FN might
      reflect two independent processes, but that variation in the FN depends more upon
      the response to rewards than losses. 

PMID- 24735734
TI  - Activation of Akt protects cancer cells from growth inhibition induced by PKM2
      knockdown.
AB  - BACKGROUND: PKM2 is an attractive target for cancer therapy, however, for many
      cancer cells, PKM2 knockdown only leads to a modest impairment of survival and
      proliferation. It is not known whether PKM2 knockdown rewires cell signaling
      pathways in these "PKM2 knockdown resistant" cells, and whether the rewired
      pathways are needed for their survival. FINDINGS: In present study, we
      investigated the effects of PKM2 knockdown on cellular signaling pathways in
      "PKM2 knockdown resistant" cancer cells. We found that knockdown of PKM2 leads to
      activation of Akt. Furthermore, we revealed that activation of Akt in PKM2
      knockdown cells is a result of glycolysis disruption. Inhibiton of PI3K-Akt
      signaling pathway leads to significant growth inhibition and apoptosis in PKM2
      knockdown cells. CONCLUSIONS: Overall, our results indicate that activation of
      Akt is necessary for the survival of PKM2 knockdown cells. Combing PKM2 knockdown
      with PI3K or Akt inhibitors may lead to a better chance to kill tumors. Our
      research may provide an unexpected opportunity for the development and
      implementation of drugs targeting cell metabolism and aberrant Akt signaling.

PMID- 24735735
TI  - US internists call for public health approach to gun violence in US.

PMID- 24735736
TI  - Non-random temporal distribution of sleep onset REM periods in the MSLT in
      narcolepsy.
AB  - STUDY OBJECTIVES: The diagnosis of narcolepsy is supported by the presence of two
      or more sleep onset REM periods (SOREMPs) in the multiple latency sleep test
      (MSLT). The distribution of SOREMPs throughout the MSLT has not been
      systematically studied in narcolepsy. We studied the temporal distribution of
      SOREMPs in the MSLT of a large series of narcoleptics and calculated the effects
      of age and the diagnostic value of shorter versions of the test. PATIENTS: 129
      patients consecutively diagnosed with narcolepsy (73.4% with cataplexy) underwent
      nocturnal polysomnography followed by a five-nap MSLT. RESULTS: 429 SOREMPs were
      recorded in 645 MSLT naps (66.5%). The probability of presenting SOREMPs in the
      fourth nap (3:30 pm) was significantly lower than in the remaining naps: 22.4%
      SOREMPs in the first nap, 20.5% in the second, 20.5% in the third, 16% in the
      fourth and 20.5% in the fifth nap (p<0.034). Patients older than 29 years had
      less SOREMPs than the younger ones (p:0.045). Shortening the MSLT to three or
      four naps decreased the capability of the test to support the diagnosis of
      narcolepsy in 14.7 and 10% respectively. CONCLUSION: The temporal distribution of
      SOREMPs in the MSLT is not even in narcolepsy, with the fourth nap having the
      lowest probability of presenting a SOREMP. This should be taken into account when
      evaluating the results of the MSLT, and particularly when using shorter versions
      of the test.

PMID- 24735737
TI  - Paraneoplastic cerebellar syndrome and sensory ganglionopathy with papillary
      thyroid carcinoma.

PMID- 24735738
TI  - Symptomatic orbital venous hypertension associated with intracranial vascular
      malformations.

PMID- 24735739
TI  - Intracranial hemorrhage in neurosarcoidosis.

PMID- 24735740
TI  - Reversible orthostatic hypotension in PICA territory cerebellar infarction.

PMID- 24735741
TI  - Advances in medical treatment of hypertrophic cardiomyopathy.
AB  - We reviewed the natural history of patients with hypertrophic cardiomyopathy
      (HCM). The effect of medical treatments on natural history, left ventricular (LV)
      functions and LV remodeling was also evaluated. Sudden cardiac death and end
      stage heart failure are the most serious complications of HCM. Age <30 years and
      a family history of sudden premature death are risk factors for sudden cardiac
      death in HCM patients. End-stage heart failure is not a specific additional
      phenomenon observed in patients with HCM, but is the natural course of the
      disease in most of those patients. After the occurrence of heart failure, the
      progression to cardiac death is very rapid. Young age at diagnosis, a family
      history of HCM, and greater wall thickness are associated with a greater
      likelihood of developing end-stage heart failure. Neither beta-blockers nor
      calcium antagonists can prevent this transition. The class Ia antiarrhythmic
      drugs, disopyramide and cibenzoline are useful for the reduction of LV pressure
      gradient. Unlike disopyramide, cibenzoline has little anticholinergic activity;
      therefore, this drug can be easily adapted to long-term use. In addition to the
      reduction in LV pressure gradient, cibenzoline can improve LV diastolic
      dysfunction, and induce regression of LV hypertrophy in patients with HCM. A
      decrease in intracellular Ca(2+) concentration through the activation of the
      Na(+)/Ca(2+) exchanger associated with cibenzoline therapy is likely to be
      closely related with the improvement in HCM-related disorders. It is possible
      that cibenzoline can prevent the progression from typical HCM to end-stage heart
      failure. 

PMID- 24735742
TI  - Effect of variable body mass on plantar foot pressure and off-loading device
      efficacy.
AB  - An increasing body of evidence has implicated obesity as having a negative effect
      on the development, treatment, and outcome of lower extremity pathologic
      entities, including diabetic foot disease. The objective of the present study was
      to increase the body of knowledge with respect to the effects of obesity on foot
      function. Specifically, we attempted to (1) describe the relationship between an
      increasing body mass index (BMI) on plantar foot pressures during gait, and (2)
      evaluate the efficacy of commonly prescribed off-loading devices with an
      increasing BMI. A repeated measures design was used to compare the peak plantar
      foot pressures under multiple test conditions, with the volunteers acting as
      their own controls. The primary outcome measure was the mean peak plantar
      pressure in the heel, midfoot, forefoot, and first metatarsal, and the 2
      variables were modification of patient weight (from "normal" BMI to "overweight,"
      "obese," and "morbidly obese") and footwear (from an athletic sneaker to a
      surgical shoe, controlled ankle motion walker, and total contact cast).
      Statistically significant increases in the peak plantar pressures were observed
      with increasing volunteer BMI weight class, regardless of the off-loading device
      used. The present investigation has provided unique and specific data with
      respect to the changes that occur in the peak plantar pressures with variable
      BMIs across different anatomic levels and with commonly used off-loading devices.
      From our results, we have concluded that although the plantar pressures increase
      with increasing weight, it appears that at least some reduction in pressure can
      be achieved with an off-loading device, most effectively with the total contact
      cast, regardless of the patient's BMI. 

PMID- 24735743
TI  - Factors associated with active aging in Finland, Poland, and Spain.
AB  - BACKGROUND: Continuous population aging has raised international policy interest
      in promoting active aging (AA). AA theoretical models have been defined from a
      biomedical or a psychosocial perspective. These models may be expanded including
      components suggested by lay individuals. This paper aims to study the correlates
      of AA in three European countries, namely, Spain, Poland, and Finland using four
      different definitions of AA. METHODS: The EU COURAGE in Europe project was a
      cross-sectional general adult population survey conducted in a representative
      sample of the noninstitutionalized population of Finland, Poland, and Spain.
      Participants (10,800) lived in the community. This analysis focuses on
      individuals aged 50 years old and over (7,987). Four definitions (two biomedical,
      one psychosocial, and a complete definition including biomedical, psychosocial,
      and external variables) of AA were analyzed. RESULTS: Differences in AA were
      found for country, age, education, and occupation. Finland scored consistently
      the highest in AA followed by Spain and Poland. Younger age was associated with
      higher AA. Higher education and occupation was associated with AA. Being married
      or cohabiting was associated with better AA compared to being widowed or
      separated in most definitions. Gender and urbanicity were not associated with AA,
      with few exceptions. Men scored higher in AA only in Spain, whereas there was no
      gender association in the other two countries. Being widowed was only associated
      with lower AA in Poland and not being married was associated with lower AA in
      Poland and Finland but not Spain. CONCLUSIONS: Associations with education,
      marital status, and occupation suggest that these factors are the most important
      components of AA. These association patterns, however, seem to vary across the
      three countries. Actions to promote AA in these countries may be addressed at
      reducing inequalities in occupation and education or directly tackling the
      components of AA lacking in each country.

PMID- 24735744
TI  - Is plasma cortisol response to stress in rainbow trout regulated by catecholamine
      induced hyperglycemia?
AB  - Based on previous studies we hypothesize that under stress conditions
      catecholamine-induced hyperglycemia contributes to enhance cortisol production in
      head kidney of rainbow trout. Therefore, treatment with propranolol (beta
      adrenoceptor blocker) should reduce the hyperglycemia elicited by stress and,
      therefore, we expected reduced glucosensing response and cortisol production in
      head kidney. Propranolol treatment was effective in blocking most of the effects
      of catecholamines in liver energy metabolism resulting in a lower glycemia in
      stressed fish. The decreased glycemia of stressed fish treated with propranolol
      was observed along with reduced transcription of genes involved in the cortisol
      synthetic pathway, which supports our hypothesis. However, changes in putative
      glucosensing parameters assessed in head kidney were scarce and in general did
      not follow changes noted in glucose levels in plasma. Furthermore, circulating
      cortisol levels did not change in parallel with changes in glycemia. As a whole,
      the present results suggest that glycemia could participate in the regulation of
      cortisol synthetic pathways but other factors are also likely involved.
      Propranolol effects on trout stress response were different depending on time
      passed after stress onset; the direct or indirect involvement of
      catecholaminergic response in the regulation of cortisol production and release
      deserves further investigation. 

PMID- 24735746
TI  - Can cone beam CT predict the hardness of interradicular cortical bone?
AB  - OBJECTIVES: Orthodontic mini implants can be inserted at the interradicular site.
      The bone quality at this site may affect the stability and anchorage of the
      implant. Bone density is clinically evaluated by Hounsfield units (HU) obtained
      from cone beam CT (CBCT). The objective of this study was to determine the
      correlations between HU, microhardness and cortical bone thickness of
      interradicular site at various segments (anterior/posterior) and aspects
      (buccal/lingual) of both jaws in a swine model. MATERIALS AND METHODS: Eight
      mandible and maxilla swine bones were scanned by CBCT. The HU and thickness of
      the above-mentioned sites were determined. Then, a Knoop microhardness test was
      applied and the Knoop Hardness Number was obtained (KHN). RESULTS: The mandible
      parameters spread over a wider range than the maxilla. The buccal aspect of the
      maxilla had higher HU and KHN values than the mandible. The lingual aspect of the
      mandible had higher KHN values than the maxilla. Posterior segments had higher HU
      and KHN values. The thickness of the alveolar cortical bone was greater in the
      maxilla than in the mandible. Correlations were found between HU and KHN for 3 of
      the 4 sites (anterior or posterior, buccal or lingual) of the mandible only. No
      correlations were found for the maxilla. Upon pooling the HU and KHN data for the
      whole jaw, correlation was found for the maxilla as well. CONCLUSIONS: Relying on
      HU values as a predictor of cortical bone hardness should be considered with
      caution.

PMID- 24735745
TI  - DNA methylation of the LY86 gene is associated with obesity, insulin resistance,
      and inflammation.
AB  - BACKGROUND: Previous genome-wide association studies (GWAS) have identified a
      large number of genetic variants for obesity and its related traits, representing
      a group of potential key genes in the etiology of obesity. Emerging evidence
      suggests that epigenetics may play an important role in obesity. It has not been
      explored whether the GWAS-identified loci contribute to obesity through
      epigenetics (e.g., DNA (deoxyribonucleic acid) methylation) in addition to
      genetics. METHOD: A multi-stage cross-sectional study was designed. We did a
      literature search and identified 117 genes discovered by GWAS for obesity and its
      related traits. Then we analyzed whether the methylation levels of these genes
      were also associated with obesity in two genome-wide methylation panels. We
      examined an initial panel of seven adolescent obese cases and seven age-matched
      lean controls, followed by a second panel of 48 adolescent obese cases and 48 age
      and gender-matched lean controls. The validated CpG sites were further
      replicated in two independent replication panels of youth (46 vs. 46 and 230
      cases vs. 413 controls, respectively) and a general population of youth,
      including 703 healthy subjects. RESULTS: One CpG site in the lymphocyte antigen
      86 (LY86) gene, which showed higher methylation in the obese in both the initial
      (p = .009) and second genome-wide DNA methylation panel (p = .008), was further
      validated in both replication panels (meta p = .00016). Moreover, in the general
      population of youth, the methylation levels of this region were significantly
      correlated with adiposity indices (p <= .02), insulin resistance (p = .001), and
      inflammatory markers (p < .001). CONCLUSION: By focusing on recent GWAS findings
      in genome-wide methylation profiles, we identified a solid association between
      LY86 gene DNA methylation and obesity.

PMID- 24735747
TI  - Management of central venous catheters in pediatric onco-hematology using 0.9%
      sodium chloride and positive-pressure-valve needleless connector.
AB  - PURPOSE: To describe, in a sample of pediatric onco-hematological patients, the
      rate of occlusions in unused central venous catheters (CVC) flushed once a week
      with a 0.9% sodium chloride solution through a positive-pressure-valve needleless
      connector. METHOD: Retrospective cohort study. Subjects aged 0-17 years were
      identified through a manual search in medical and nursing records and were
      observed for two years or until the occurrence of one of the following events:
      start or resume of continuous infusion; CVC removal; death. The primary study
      outcome was the frequency of CVC occlusion (partial or complete). RESULTS: Fifty
      one patients were identified (median age 6 years). The median duration of follow
      up was 169 days (IQR 111-305). During the follow up period, 14 patients (27%) had
      one CVC occlusion, in 2 cases (4%) the occlusion was complete, in 12 (23%)
      partial. All the occlusions were solved without the need for catheter removal.
      The lumen diameter <= 4.2 vs > 4.2 French showed a statistically significant
      association with occlusion at multivariate analysis (OR 4.0; 95% CI 1.1-14.7).
      CONCLUSIONS: Our findings are reassuring with respect to the management of the
      CVC using the adopted protocol. The study provides useful information for patient
      care, by verifying the performance of the adopted CVC management protocol and by
      identifying critical areas for nursing care.

PMID- 24735748
TI  - Dorsal root ganglion electrical stimulation promoted intertransverse process
      spinal fusion without decortications and bone grafting: a proof-of-concept study.
AB  - BACKGROUND CONTEXT: Periosteum, endosteum, and bone are innervated by sensory
      nerves expressing calcitonin gene-related peptide (CGRP), which is a known
      osteoanabolic peptide and plays an important role in fracture healing and spinal
      fusion. Synthesis and release of CGRP are found in sensory neurons located in the
      dorsal root ganglions (DRGs) and can be upregulated by electrical stimulation
      (ES) at DRG. PURPOSE: To prove our study hypothesis on the potential of precise
      ES at DRG through implantable microelectrical stimulation system (IMESS) for its
      effect on promoting spinal fusion in a rat model without decortications and bone
      grafting. STUDY DESIGN: An experimental animal study. METHODS: A novel IMESS was
      developed for stimulating L4-L6 DRG in rats. Sixteen rats were used and divided
      equally into the control group without ES and the ES group, with a daily 20
      minutes ES to DRG for 6 weeks. At the end of 6 weeks, radiography and
      microcomputed tomography were conducted to evaluate new bone formation and spinal
      fusion. Bilateral L4-L6 DRGs were harvested for immunohistochemistry and
      quantification of neurons with upregulated CGRP expression. RESULTS: In the ES
      group, rate of radiographic fusion with complete and uninterrupted bony bridging
      was 100% (8/8) at the right L4/L5 transverse processes and 75% (6/8) at the right
      L5/L6 transverse processes. Bony callus formation was absent at the left L4-L6
      transverse processes in the ES group and in bilateral L4-L6 transverse processes
      in the control group. CONCLUSIONS: We proved for the first time that precise ES
      at DRG through IMESS effectively promoted intertransverse process fusion in rat
      model without decortications and bone grafting. Electrical stimulation at DRG
      might be an attractive minimal invasive bioengineering approach and an
      alternative therapy for intertransverse process fusion that is increasingly being
      used for the treatment of degenerative spine disorders.

PMID- 24735749
TI  - Catalytic control in terpenoid cyclases: multiscale modeling of thermodynamic,
      kinetic, and dynamic effects.
AB  - In this Opinion we review some of the key work on terpene biosynthesis using
      multi-scale simulation approaches. Terpene synthases generate terpenes employing
      beautiful and rich carbocation chemistry, including highly specific ring
      formations, hydride, proton, methyl, and methylene migrations, followed by
      reaction quenching. In spite of the chemical finesse of these enzymes, terpene
      synthases are highly promiscuous. Incidentally, these mischievous enzymes are
      very challenging to treat computationally due to the inherent complexity of the
      potential energy surface in carbocations and the lack of directional hydrogen
      bonds to active site residues. Thus, a carefully designed computational platform
      must be employed. Herein, we review multi-scale simulations of squalene-hopene,
      aristolochene, and bornyl diphosphate synthases, and highlight what we have
      learned from this work. 

PMID- 24735750
TI  - The past, present and future of breast cancer research in China.
AB  - The incidence of breast cancer has increased rapidly in recent years and has now
      become the most common cancer in women in major cities of China. Here, we
      reviewed the history and progress of breast cancer research in China, including
      achievements that Chinese scientists have made in basic, translational and
      clinical research. Moreover, we evaluated the contributions of National Natural
      Science Foundation of China (NSFC) in the field of breast cancer research. The
      number of grants funded by the NSFC for breast cancer has tripled from 87 to 274
      in the past 5years, and this resulted in a dramatic increase in breast cancer
      publications. Despite this great progress, policy makers are continuously taking
      efforts to guarantee the transparency of grant competition and the effective use
      of NSFC finding. 

PMID- 24735751
TI  - A sorafenib derivative and novel SHP-1 agonist, SC-59, acts synergistically with
      radiotherapy in hepatocellular carcinoma cells through inhibition of STAT3.
AB  - Radiotherapy shows limited benefit as treatment for hepatocellular carcinoma
      (HCC). In this study, we aimed to overcome the radioresistance of HCC by using a
      novel sorafenib derivative, SC-59 that targets SHP-1-related signaling. HCC cell
      lines (SK-Hep1, Hep3B, and Huh7) were treated with sorafenib, SC-59, radiation,
      sorafenib plus radiation, or SC-59 plus radiation, and then apoptosis, colony
      formation, signal transduction and the phosphatase activity were analyzed. The
      synergistic effect of radiotherapy and SC-59 was analyzed using a combination
      index (CI) approach. In vivo efficacy was determined in a Huh7-bearing
      subcutaneous model. Mice were treated with radiation (5 Gy, one fraction per day)
      for 4 days, SC-59 (10mg/kg/day) for 24 days, or a combination. Tumor samples were
      further analyzed for p-STAT3 and SHP-1 activity. SC-59 displayed a better
      synergistic effect when used in combination with radiotherapy than sorafenib in
      HCC cell lines. SC-59 downregulated p-STAT3 and its downstream targets and
      increased SHP-1 phosphatase activity. Both ectopic STAT3 and inhibition of SHP-1
      abolished SC-59-induced radiosensitization. Moreover, SC-59 significantly
      synergized radiotherapy in a Huh7 xenograft model by targeting SHP-1/STAT3
      signaling. The novel sorafenib derivative, SC-59, acting as a SHP-1 agonist,
      displays a better synergistic effect when used in combination with radiotherapy
      than sorafenib for the treatment of HCC. Further clinical investigation is
      warranted.

PMID- 24735752
TI  - Inhibiting glucosylceramide synthase facilitates the radiosensitizing effects of
      vinorelbine in lung adenocarcinoma cells.
AB  - The standard treatment regimen for patients diagnosed with non-small cell lung
      cancer (NSCLC) with locally advanced stage III disease is concurrent
      chemoradiotherapy (CCRT). This study investigated the molecular effects of vinca
      alkaloid vinorelbine (VNR)-based CCRT. We reviewed the records of 68 patients
      with stage III NSCLC: 42 patients received VNR-based CCRT, and 26 were treated
      with radiation alone. Human lung adenocarcinoma cells were used in this study to
      investigate the molecular effects of glucosylceramide synthase inhibition on VNR
      based CCRT. There was response rate of 66.7% with CCRT, which was better than the
      response rate observed with radiation alone (30.8%; P<0.001). CCRT caused an
      increase in cell cycle arrest at G2/M phase accompanied by apoptosis. Oxidative c
      Jun N-terminal kinase (JNK) activation was involved in the increased apoptosis
      levels but not the cell cycle arrest. CCRT also induced an increase in ceramide
      accompanied by a decrease in glucosylceramide that was positively correlated with
      the cytotoxic effects. Pharmacologically inhibiting glucosylceramide synthase
      facilitated VNR- and CCRT-induced apoptosis by promoting the JNK pathway.
      Inhibiting glucosylceramide synthase facilitates the radiosensitizing effects of
      VNR by promoting JNK-mediated apoptosis in lung adenocarcinoma cells.

PMID- 24735753
TI  - The effect of phenobarbitone on cognition in adult patients with new onset
      epilepsy: a multi-centric prospective study from India.
AB  - OBJECTIVE: In view of the conflicting results of cognitive and behavioral
      consequences of PB, the present study was planned to analyze its efficacy, serial
      neuropsychological functions and its impact on psychosocial functioning in adults
      with epilepsy while on phenobarbitone (PB). METHODOLOGY: This prospective multi
      centric study carried out across 4 centers in India included 75 adult patients of
      >=18 years (M:F=52:23; age: 27.3 +/- 8.5 years) with epilepsy who were prescribed
      phenobarbitone and underwent serial standardized neuropsychological assessment
      (NIMHANS battery for adults) at baseline, 1 month, 3 months, 6 months and 12
      months. The demographic, seizure details and outcome measures were recorded.
      RESULTS: Of the 75 patients, 63 had completed clinical and neuropsychological
      assessment, i.e. visit 1 (baseline), visit 4 (6 months) and visit 5 (12 months).
      There was no deterioration rather an improvement during the follow visits in all
      the neuropsychological functions. The results indicate that 16 neuropsychological
      variables changed significantly, viz. mental speed (p<0.001), sustained attention
      (p<0.001), focused attention (p<0.002), planning (p<0.001), concept formation
      (p<0.05), set shifting (p<0.001), verbal learning (p<0.0001), verbal memory
      (p<0.0001), visual memory (p<0.0001) and intelligence (p<0.001). The scales
      measuring the outcome of psychosocial functioning significantly changed during
      follow up included happiness (p<0.002), Impact of Epilepsy on patient's life
      (p<0.02), A-B Neuropsychological Assessment (p<0.015), HADS anxiety (p<0.001) and
      emotional disorder (p<0.006). There was a significant reduction in seizure
      severity as measured by Liverpool Seizure Severity Scale (p<0.002) and seizure
      freedom was maintained. CONCLUSIONS: This study demonstrated that phenobarbitone
      is effective, well tolerated AED and do not have cognitive impairment over one
      year. There was variable but distinct improvement in cognition and psychosocial
      functioning, and effective seizure control could be one of the factor for it.

PMID- 24735755
TI  - Sensitizing properties of proteins: executive summary.
AB  - The scope of allergy risk is diverse considering the myriad ways in which protein
      allergenicity is affected by physiochemical characteristics of proteins. The
      complexity created by the matrices of foods and the variability of the human
      immune system add additional challenges to understanding the relationship between
      sensitization potential and allergy disease. To address these and other issues,
      an April 2012 international symposium was held in Prague, Czech Republic, to
      review and discuss the state-of-the-science of sensitizing properties of protein
      allergens. The symposium, organized by the Protein Allergenicity Technical
      Committee of the International Life Sciences Institute's Health and Environmental
      Sciences Institute, featured presentations on current methods, test systems,
      research trends, and unanswered questions in the field of protein sensitization.
      A diverse group of over 70 interdisciplinary scientists from academia,
      government, and industry participated in the symposium. Experts provided
      overviews on known mechanisms by which proteins in food may cause sensitization,
      discussed experimental models to predict protein sensitizing potential, and
      explored whether such experimental techniques may be applicable in regulatory
      settings. Three accompanying reviews address critical factors and methods for
      assessing allergic sensitization: 1) food-and protein-related factors; 2) host
      specific factors and 3) screening methods, i.e., the ability of experimental
      models to predict the sensitizing potential of proteins and whether such models
      are applicable within regulatory settings. 

PMID- 24735754
TI  - Identification of mRNAs and lincRNAs associated with lung cancer progression
      using next-generation RNA sequencing from laser micro-dissected archival FFPE
      tissue specimens.
AB  - OBJECTIVES: Adenocarcinoma in situ (AIS) is an intermediate step in the
      progression of normal lung tissue to invasive adenocarcinoma. However, molecular
      mechanisms underlying this progression remain to be fully elucidated due to
      challenges in obtaining fresh clinical samples for downstream analyses. Formalin
      fixation and paraffin embedding (FFPE) is a tissue preservation system widely
      used for long-term storage. Until recently, challenges in working with FFPE
      precluded using new RNA sequencing technologies (RNA-seq), which would help
      clarify key pathways in cancer progression. Also, isolation techniques including
      laser-capture micro-dissection provide the ability to select histopathologically
      distinct tissues, allowing researchers to study transcriptional variations
      between tightly juxtaposed cell and tissue types. MATERIALS AND METHODS:
      Utilizing these technologies and new alignment tools we examined differential
      expression of long intergenic non-coding RNAs (lincRNAs) and mRNAs across normal,
      AIS and invasive adenocarcinoma samples from six patients to identify possible
      markers of lung cancer progression. RESULTS: RNA extracted and sequenced from
      these 18 samples generated an average of 198 million reads per sample. After
      alignment and filtering, uniquely aligned reads represented an average 35% of the
      total reads. We detected differential expression of a number of lincRNAs and
      mRNAs when comparing normal to AIS, or AIS to invasive adenocarcinoma. Of these,
      5 lincRNAs and 31 mRNAs were consistently up- or down-regulated from normal to
      AIS and more so to invasive carcinoma. We validated the up-regulation of two
      mRNAs and one lincRNA by RT-qPCR as proof of principle. CONCLUSION: Our findings
      indicate a potential role of not only mRNAs, but also lincRNAs in the progression
      to invasive adenocarcinoma. We anticipate that these findings will lay the
      groundwork for future experimental studies of candidate RNAs from FFPE to
      identify their functional roles in lung cancer.

PMID- 24735756
TI  - 24/7/365 in-house radiologist coverage: effect on resident education.
AB  - RATIONALE AND OBJECTIVES: To compare programs with and without 24-hour/7 days a
      week/365 days a year (24/7/365) in-house radiologist coverage regarding resident
      perceptions of their on-call experience, volume of resident dictations on call,
      and report turnaround time. MATERIALS AND METHODS: Residents from six academic
      radiology departments were invited to participate in an 11-item online survey.
      Survey items were related to workload, level of autonomy, faculty feedback,
      comfort level, faculty supervision, and overall educational experience while on
      call from 8 pm to 8 am. Each site provided data on imaging volume, radiologist
      coverage, volume of examinations dictated by residents, number of residents on
      call, and report turnaround time from 8 pm to 8 am. F-ratios and eta-squares were
      calculated to determine the relationships between dependent and independent
      variables. A P value < .05 was considered statistically significant. RESULTS: A
      total of 146 (67%) of 217 residents responded. Residents in programs with
      24/7/365 in-house radiologist coverage dictated a lower percentage of
      examinations (46%) compared with other residents (81%) and rated faculty feedback
      more positively (mean 3.8 vs. 3.3) but rated their level of autonomy (mean 3.6
      vs. 4.5) and educational experience (mean 3.6 vs. 4.2) more negatively (all P <
      .05). Report turnaround time was lower in programs with 24/7/365 coverage than
      those without (mean 1.7 hours vs. 9.1 hours). The majority of resident comments
      were negative and related to loss of autonomy with 24/7/365 coverage. CONCLUSION:
      More rapid report turnaround time related to 24/7/365 coverage may come at the
      expense of resident education.

PMID- 24735757
TI  - Socio-demographic determinants and access to prenatal care in Italy.
AB  - BACKGROUND: Many governments have made commitments to examine inequalities in
      healthcare access based on studies assessing the association between several
      socio-demographic factors and late initiation or fewer prenatal examinations.
      This study addressed the question of whether socio-demographic determinants were
      significant in explaining differences in prenatal care in one administrative
      region of Italy, Umbria. METHODS: Data were obtained from the administrative
      source of the regional Standard Certificate of Live Births between 2005 and 2010,
      and were merged with Census data to include a socio-economic deprivation index.
      Standard and multilevel logistic regression models were used to analyze the
      magnitude of various individual-level maternal characteristics and socio
      demographic indicators, such as nationality, employment status, education with
      respect to late access to the first examination, and low number of medical
      visits. RESULTS: The study involved approximately 37,000 women. The heterogeneous
      effects of socio-demographic variables were documented on the prenatal care
      indicators analyzed. A multivariate model showed that women born outside Italy
      had a higher probability of making their first visit later than the 12th week of
      pregnancy and low numbers of prenatal medical visits; the estimated odds ratio
      for the analyzed indicators range from 2.25 to 3.05. Inadequate prenatal
      healthcare use was also observed in younger and pluriparous women and those with
      low education; in addition, having a job improved the use of services, possibly
      through transmission of information of negative consequences due to delayed or
      few prenatal visits. Interestingly, this study found a substantial reduction in
      the number of pregnant women who do not use prenatal healthcare services
      properly. CONCLUSIONS: The aim of this research is to provide more accurate
      knowledge about the inadequate use of prenatal healthcare in Italy. Results
      highlight the existence of differences in healthcare use during pregnancy,
      especially for women from less advantaged social classes (i.e., unemployed or
      poorly educated). Such inequalities should be examined in all areas of public
      policy and public services, to ensure equal opportunity for their use.

PMID- 24735759
TI  - The impact of implementation of the Canadian regulatory requirements on the
      quality of natural health products: the glucosamine case.
AB  - PURPOSE: We investigated whether the recent implementation of the regulatory
      requirements for the entry to the Canadian market of natural products has
      resulted in improved quality of the available glucosamine products. METHODS:
      Eleven available products, of which 8 had been tested in 2002 (7 had contained
      substantially lower than the label claim of the active ingredient), and a
      European pharmaceutical grade tablet were assayed for their glucosamine content.
      The potassium and sodium contents of the products were also tested. RESULTS: Nine
      of the 11 Canadian products and the European tablet had more than 91% of the
      label claim of the active ingredient, hence, met the criterion. Two products
      contained 71 and 78% label claim. The electrolyte contents were very variable but
      constituted only a small fraction of the daily requirements. CONCLUSION: Most
      tested glucosamine products passed the Health Canada requirements. This
      improvement is likely due to the publicity regarding the low quality of the
      products in the past and also a result, at least in part, of the introduction of
      the new regulatory requirements. The sub-standard quality of a few tested
      products is still of concern.

PMID- 24735758
TI  - Application of Caco-2 cell line in herb-drug interaction studies: current
      approaches and challenges.
AB  - The Caco-2 model is employed in pre-clinical investigations to predict the likely
      gastrointestinal permeability of drugs because it expresses cytochrome P450
      enzymes, transporters, microvilli and enterocytes of identical characteristics to
      the human small intestine. The FDA recommends this model as integral component of
      the Biopharmaceutics Classification System (BCS). Most dedicated laboratories use
      the Caco-2 cell line to screen new chemical entities through prediction of its
      solubility, bioavailability and the possibility of drug-drug or herb-drug
      interactions in the gut lumen. However, challenges in the inherent
      characteristics of Caco-2 cell and inter-laboratory protocol variations have
      resulted to generation of irreproducible data. These limitations affect the
      extrapolation of data from pre-clinical research to clinical studies involving
      drug-drug and herb-drug interactions. This review addresses some of these caveats
      and enumerates the plausible current and future approaches to reduce the
      anomalies associated with Caco-2 cell line investigations focusing on its
      application in herb-drug interactions.

PMID- 24735760
TI  - Alteration of pharmacokinetics of grepafloxacin in type 2 diabetic rats.
AB  - PURPOSE: Patients with type 2 diabetes are generally treated with various
      pharmacological compounds and are exposed to a high risk of drug-drug
      interactions. However, alterations of pharmacokinetics in a type 2 diabetes model
      have been obscure. The present study was undertaken to investigate the effects of
      type 2 diabetes on the pharmacokinetics of the fluoroquinolone grepafloxacin
      (GPFX) and the expression level of P-glycoprotein (P-gp), one of the drug efflux
      transporters. METHODS: We used Goto-Kakizaki (GK) rats, a lean model of type 2
      diabetes. Plasma concentration and intestinal, renal, and biliary clearance of
      GPFX were measured after intravenous and intraintestinal administration in Wistar
      and GK rats. Real-time PCR and Western blotting were used to assess mRNA and
      protein expression levels. RESULTS: We found a significant increase in the plasma
      concentrations of GPFX at 90, 120 and 240 minutes after intraintestinal
      administration in GK rats compared with the concentrations in Wistar rats but not
      after intravenous administration. The increase in plasma GPFX concentration was
      associated with reduction in jejunal clearance of GPFX caused by a decrease in
      secretory transport of GPFX. However, there was no correlation between the
      decrease in secretory transport of GPFX and P-gp expression level. CONCLUSION:
      Type 2 diabetic conditions alter P-gp function as well as expression level and
      correlate poorly with each other.

PMID- 24735762
TI  - Karanjin interferes with ABCB1, ABCC1, and ABCG2.
AB  - PURPOSE: The prominent ATP-binding cassette (ABC) transporters ABCB1, ABCC1, and
      ABCG2 are involved in substance transport across physiological barriers and
      therefore in drug absorption, distribution, and elimination. They also mediate
      multi-drug resistance in cancer cells. Different flavonoids are known to
      interfere with different ABC transporters. Here, the effect of the furanoflavonol
      karanjin, a potential drug with antiglycaemic, gastroprotective, antifungal, and
      antibacterial effects, was investigated on ABCB1, ABCC1, and ABCG2-mediated drug
      transport in comparison to the flavonoids apigenin, genistein, and naringenin.
      METHODS: Cells expressing the relevant transporters (ABCB1: UKF-NB-3(ABCB1), UKF
      NB-3(r)VCR10; ABCC1: G62, PC-3(r)VCR20; ABCG2: UKF-NB-3(ABCG2)) were used in
      combination with specific fluorescent and cytotoxic ABC transporter substrates
      and ABC transporter inhibitors to study ABC transporter function. Moreover, the
      effects of the investigated flavonoids were determined on the ABC transporter
      ATPase activities. RESULTS: Karanjin interfered with drug efflux mediated by
      ABCB1, ABCC1, and ABCG2 and enhanced the ATPase activity of all three
      transporters. Moreover, karanjin exerted more pronounced effects than the control
      flavonoids apigenin, genistein, and naringenin on all three transporters. Most
      notably, karanjin interfered with ABCB1 at low concentrations being about 1 uM.
      CONCLUSIONS: Taken together, these findings should be taken into account during
      further consideration of karanjin as a potential drug for different therapeutic
      indications. The effects on ABCB1, ABCC1, and ABCG2 may affect the
      pharmacokinetics of co-administered drugs.

PMID- 24735763
TI  - Prediction of oral absorption of low-solubility drugs by using rat simulated
      gastrointestinal fluids: the importance of regional differences in membrane
      permeability and solubility.
AB  - PURPOSE: This study aimed to develop a novel approach for predicting the oral
      absorption of low-solubility drugs by considering regional differences in
      solubility and permeability within the gastrointestinal (GI) tract. METHODS:
      Simulated GI fluids were prepared to reflect rat in vivo bile acid and
      phospholipid concentrations in the upper and lower small intestine. The saturated
      solubility and permeability of griseofulvin (GF) and albendazole (AZ), a drug
      with low aqueous solubility, were measured using these simulated fluids, and
      fraction absorbed (Fa) at time t after oral administration was calculated.
      RESULTS: The saturated solubility of GF and AZ, a drug with low aqueous
      solubility, differed considerably between the simulated GI fluids. Large regional
      differences in drugs concentration were also observed following oral
      administration in vivo. The predicted Fa values using solubility and permeability
      data of the simulated GI fluid were found to correspond closely to the in vivo
      data. CONCLUSION: These results indicated the importance of evaluating regional
      differences in drug solubility and permeability in order to predict oral
      absorption of low-solubility drugs accurately. The new methodology developed in
      the present study could be useful for new oral drug development.

PMID- 24735764
TI  - Effects of long-term hepatic ischemia-reperfusion injury on the function of P
      glycoprotein in vivo in rats.
AB  - PURPOSE: Ischemia-reperfusion injury is a common complication in liver surgery
      with oxidative stress related graft failure as a potential complication. The
      oxidative stress could affect hepatic drug transporters such as P-glycoprotein,
      which is crucial in the hepatic clearance of certain immunosuppressant drugs.
      Thus,, it is important to study its function after ischemia-reperfusion injury in
      vivo. Rhodamine 123 is a fluorescent substrate of P-glycoprotein and its hepatic
      disposition can be visualized using multiphoton microscopy in vivo using
      anaesthetized animals. The aim of this study was to investigate the effect of
      long-term ischemia-reperfusion injury on P-glycoprotein function in hepatocytes
      using in vivo multiphoton microscopy. METHODS: Localized ischemia was induced for
      1 hour in rats. The liver was reperfused for 4, 24, 48 hours or 1 week, where
      after rhodamine 123 was injected intravenously. Multiphoton microscopy imaged the
      liver and bile was collected continuously up to 6 hours following drug
      administration. The liver was harvested for histology and protein expression of P
      glycoprotein. RESULTS: Ischemia-reperfusion injury resulted in extensive liver
      damage, inflammatory cell infiltration and apoptosis in the midzonal and
      centrilobular regions of the liver acinus. P-glycoprotein protein expression
      decreased. Cellular concentration of rhodamine 123 increased as visualized by
      multiphoton microscopy, which was confirmed with decreased excretion of rhodamine
      123 in collected bile. CONCLUSIONS: This study showed reduced function of P
      glycoprotein in ischemia-reperfusion injury as reflected by decreased biliary
      excretion of Rhodamine 123, as well as reduced protein expression of the
      transporter. Multiphoton microscopy could be used to visualize and quantitate the
      intracellular levels of rhodamine 123. These findings stipulate the importance of
      using multiphoton microscopy to understand transmembrane drug flux and reflect on
      careful drug dosing after hepatic surgery.

PMID- 24735765
TI  - High intensity focused ultrasound technology, its scope and applications in
      therapy and drug delivery.
AB  - Ultrasonography is a safe, inexpensive and wide-spread diagnostic tool capable of
      producing real-time non-invasive images without significant biological effects.
      However, the propagation of higher energy, intensity and frequency ultrasound
      waves through living tissues can induce thermal, mechanical and chemical effects
      useful for a variety of therapeutic applications. With the recent development of
      clinically approved High Intensity Focused Ultrasound (HIFU) systems, therapeutic
      ultrasound is now a medical reality. Indeed, HIFU has been used for the thermal
      ablation of pathological lesions; localized, minimally invasive ultrasound
      mediated drug delivery through the transient formation of pores on cell
      membranes; the temporary disruption of skin and the blood brain barrier; the
      ultrasound induced break-down of blood clots; and the targeted release of drugs
      using ultrasound and temperature sensitive drug carriers. This review seeks to
      engage the pharmaceutical research community by providing an overview on the
      biological effects of ultrasound as well as highlighting important therapeutic
      applications, current deficiencies and future directions.

PMID- 24735761
TI  - Understanding the hysteresis loop conundrum in pharmacokinetic/pharmacodynamic
      relationships.
AB  - Hysteresis loops are phenomena that sometimes are encountered in the analysis of
      pharmacokinetic and pharmacodynamic relationships spanning from pre-clinical to
      clinical studies. When hysteresis occurs it provides insight into the complexity
      of drug action and disposition that can be encountered. Hysteresis loops suggest
      that the relationship between drug concentration and the effect being measured is
      not a simple direct relationship, but may have an inherent time delay and
      disequilibrium, which may be the result of metabolites, the consequence of
      changes in pharmacodynamics or the use of a non-specific assay or may involve an
      indirect relationship. Counter-clockwise hysteresis has been generally defined as
      the process in which effect can increase with time for a given drug
      concentration, while in the case of clockwise hysteresis the measured effect
      decreases with time for a given drug concentration. Hysteresis loops can occur as
      a consequence of a number of different pharmacokinetic and pharmacodynamic
      mechanisms including tolerance, distributional delay, feedback regulation, input
      and output rate changes, agonistic or antagonistic active metabolites, uptake
      into active site, slow receptor kinetics, delayed or modified activity, time
      dependent protein binding and the use of racemic drugs among other factors. In
      this review, each of these various causes of hysteresis loops are discussed, with
      incorporation of relevant examples of drugs demonstrating these relationships for
      illustrative purposes. Furthermore, the effect that pharmaceutical formulation
      has on the occurrence and potential change in direction of the hysteresis loop,
      and the major pharmacokinetic / pharmacodynamic modeling approaches utilized to
      collapse and model hysteresis are detailed.

PMID- 24735766
TI  - Differential effects of the oncogenic BRAF inhibitor PLX4032 (vemurafenib) and
      its progenitor PLX4720 on ABCB1 function.
AB  - PURPOSE: The clinically approved oncogenic BRAF inhibitor PLX4032 (vemurafenib)
      was shown to be a substrate of the ATP-binding cassette (ABC) transporter ABCB1.
      Here, we compared PLX4032 and its structurally closely related precursor compound
      PLX4720 for their interference with ABCB1 and the ABCB1-mediated compound
      transport using docking and cell culture experiments. METHODS: For the docking
      study of PLX4032 and PLX4720 with ABCB1, we analysed binding of both compounds to
      mouse Abcb1a and to human ABCB1 using a homology model of human ABCB1 based on
      the 3D structure of Abcb1a. Naturally ABCB1 expressing cells including V600E BRAF
      mutated and BRAF wild-type melanoma cells and cells transduced with a lentiviral
      vector encoding for ABCB1 were used as cell culture models. ABCB1 expression and
      function were studied by the use of fluorescent and cytotoxic ABCB1 substrates in
      combination with ABCB1 inhibitors. RESULTS: Docking experiments predicted PLX4032
      to interact stronger with ABCB1 than PLX4720. Experimental studies using
      different cellular models and structurally different ABCB1 substrates confirmed
      that PLX4032 interfered stronger with ABCB1 function than PLX4720. For example,
      PLX4032 (20 uM) induced a 4-fold enhanced rhodamine 123 accumulation compared to
      PLX4720 (20 uM) in ABCB1-transduced UKF-NB-3 cells and reduced the IC50 for the
      cytotoxic ABCB1 substrate vincristine in this model by 21-fold in contrast to a 9
      fold decrease induced by PLX4720. CONCLUSIONS: PLX4032 exerted stronger effects
      on ABCB1-mediated drug transport than PLX4720. This indicates that small changes
      in a molecule can substantially modify its interaction with ABCB1, a promiscuous
      transporter that transports structurally different compounds.

PMID- 24735767
TI  - Dosimetric advantages of a "butterfly" technique for intensity-modulated
      radiation therapy for young female patients with mediastinal Hodgkin's lymphoma.
AB  - PURPOSE: High cure rates for Hodgkin's lymphoma must be balanced with long-term
      treatment-related toxicity. Here we report an intensity-modulated radiation
      therapy (IMRT) technique that achieves adequate target coverage for mediastinal
      disease while minimizing high- and low-dose exposure of critical organs. METHODS
      AND MATERIALS: Treatment plans for IMRT and conventional anteroposterior
      posteroanterior (AP-PA) techniques, with comparable coverage of the planning
      target volume (PTV), were generated for 9 female patients with mediastinal
      Hodgkin's lymphoma assuming use of inclined positioning, daily breath-hold, and
      CT-on-rails verification. Our "butterfly" IMRT beam arrangement involved anterior
      beams of 300 degrees -30 degrees  and posterior beams of 160 degrees -210 degrees
      . Percentages of normal structures receiving 30 Gy (V30), 20 Gy (V20), and 5 Gy
      (V5) were tabulated for the right and left breasts, total lung, heart, left and
      right ventricles, left anterior descending coronary artery (LAD), and spinal
      cord. Differences in each variable, conformity index, homogeneity index, and
      V107% between the two techniques were calculated (IMRT minus conventional).
      RESULTS: Use of IMRT generally reduced the V30 and V20 to critical structures: 
      1.4% and +0.1% to the right breast, -1.7% and -0.9% to the left breast, -14.6%
      and -7.7% to the total lung, -12.2% and -10.5% to the heart, -2.4% and -14.2% to
      the left ventricle, -16.4% and -8.4% to the right ventricle, -7.0% and -14.2% to
      the LAD, and -52.2% and -13.4% to the spinal cord. Differences in V5 were +6.2%
      for right breast, +2.8% for left breast, +12.9% for total lung, -3.5% for heart, 
      8.2% for left ventricle, -1.5% for right ventricle, +0.1% for LAD, and -0.1% for
      spinal cord. Use of IMRT significantly reduced the volume of tissue receiving
      107% of the dose (mean 754 cm3 reduction). CONCLUSIONS: This butterfly technique
      for IMRT avoids excess exposure of heart, breast, lung, and spinal cord to doses
      of 30 or 20 Gy; mildly increases V5 to the breasts; and decreases the V107%.

PMID- 24735768
TI  - Associations between sugar-sweetened beverage consumption and fast-food
      restaurant frequency among adolescents and their friends.
AB  - OBJECTIVE: To assess associations between adolescents and their friends with
      regard to sugar-sweetened beverage (SSB)/diet soda intake and fast-food (FF)
      restaurant visits. DESIGN: Population-based, cross-sectional survey study with
      direct measures from friends. SETTING: Twenty Minneapolis/St Paul schools during
      2009-2010. PARTICIPANTS: Adolescents (n = 2,043; mean age, 14.2 +/- 1.9 years;
      46.2% female; 80% non-white). MAIN OUTCOME MEASURES: Adolescent SSB/diet soda
      intake and FF visits. ANALYSIS: Generalized estimating equation logistic models
      were used to examine associations between adolescents' SSB/diet soda intake and
      FF visits and similar behaviors in nominated friends (friend groups and best
      friends). School-level (middle vs high school) interactions were assessed.
      RESULTS: Significant associations were found between adolescents and friends
      behaviors for each of the beverages assessed (P < .05), but they varied by
      friendship type and school level. Five of 6 models of FF visits (including all FF
      visits) were significantly associated (P < .05) among adolescents and their
      friends. Significant interactions by school level were present among adolescents'
      and friends' FF visits, with associations generally for high school participants
      compared with middle school participants (P < .05). CONCLUSIONS AND IMPLICATIONS:
      Findings suggest that for many beverages and FF restaurant types, friends'
      behaviors are associated, especially FF visits for older adolescents. Nutrition
      education efforts may benefit by integrating knowledge of the impact of
      adolescents' friends on FF visits.

PMID- 24735769
TI  - Is planning for driving cessation critical for the well-being and lifestyle of
      older drivers?
AB  - BACKGROUND: Driving cessation has demonstrated impacts on well-being and
      lifestyle. Despite the recognized reluctance of older people to plan for driving
      cessation, this study has identified a new group who has a stated plan to stop
      driving within 12 months. Although gradual reduction of driving has been
      documented as part of the usual driving cessation, this study explored the
      differences between retired drivers and those with a stated plan to retire within
      12 months in sociodemographic, well-being and lifestyle outcomes. METHODS: This
      study extracted all baseline data from a clinical trial exploring the
      effectiveness of a group program for older retiring and retired drivers.
      Sociodemographic data included age, gender, health status, educational level, and
      living situation. All participants completed measures related to episodes away
      from home, well-being, and lifestyle. These were compared using parametric and
      nonparametric statistical analysis. RESULTS: Participants (n = 131) included 68
      retired drivers (mean age 79.8 years) and 63 retiring drivers (mean age 77.8
      years). Retiring drivers engaged in more episodes away from home (p = 0.03), and
      more social activities (p = 0.02), used less alternative transport (p < 0.001),
      displayed fewer anxiety (p = 0.05), and depressive (p = 0.01) symptoms, but
      demonstrated lower transport and lifestyle self-efficacy (p = 0.04). CONCLUSION:
      Both retired and retiring drivers require support for driving cessation and
      community engagement. Retiring drivers may be in a critical position to engage in
      driving cessation interventions to improve self-efficacy and begin adapting
      community mobility.

PMID- 24735770
TI  - All public services must learn lessons from Mid Staffs on handling complaints,
      MPs say.

PMID- 24735772
TI  - Automation of a high risk medication regime algorithm in a home health care
      population.
AB  - OBJECTIVE: Create an automated algorithm for predicting elderly patients'
      medication-related risks for readmission and validate it by comparing results
      with a manual analysis of the same patient population. MATERIALS AND METHODS:
      Outcome and Assessment Information Set (OASIS) and medication data were reused
      from a previous, manual study of 911 patients from 15 Medicare-certified home
      health care agencies. The medication data was converted into standardized drug
      codes using APIs managed by the National Library of Medicine (NLM), and then
      integrated in an automated algorithm that calculates patients' high risk
      medication regime scores (HRMRs). A comparison of the results between algorithm
      and manual process was conducted to determine how frequently the HRMR scores were
      derived which are predictive of readmission. RESULTS: HRMR scores are composed of
      polypharmacy (number of drugs), Potentially Inappropriate Medications (PIM)
      (drugs risky to the elderly), and Medication Regimen Complexity Index (MRCI)
      (complex dose forms, instructions or administration). The algorithm produced
      polypharmacy, PIM, and MRCI scores that matched with 99%, 87% and 99% of the
      scores, respectively, from the manual analysis. DISCUSSION: Imperfect match rates
      resulted from discrepancies in how drugs were classified and coded by the manual
      analysis vs. the automated algorithm. HRMR rules lack clarity, resulting in
      clinical judgments for manual coding that were difficult to replicate in the
      automated analysis. CONCLUSION: The high comparison rates for the three measures
      suggest that an automated clinical tool could use patients' medication records to
      predict their risks of avoidable readmissions.

PMID- 24735771
TI  - A novel "salting-out" procedure for the isolation of tumor-derived exosomes.
AB  - The last decade has seen an exponential growth in the number of exosome-related
      publications. Although many of these studies have used exosomes from biological
      fluids (blood, and ascites or pleural effusions) the vast majority employed
      vesicles isolated from large volumes of tissue culture supernatants. While
      several techniques are available for their isolation, all require a significant
      reduction in volume to obtain sufficient concentrations for study. One approach
      is to concentrate the medium before proceeding with their isolation, however,
      these procedures are very time consuming and require specialized laboratory
      equipment. Here we provide a new and effective method for the isolation of tumor
      derived exosomes based on "charge neutralization" with acetate. We show that
      titration of tissue culture supernatants with 0.1M acetate to pH4.75 results in
      immediate precipitation of virtually all the exosomes. The precipitated exosomes
      can be washed to remove residual media and are readily "resolubilized" upon
      resuspension in acetate-free buffer at neutral pH. This simple cost effective
      method significantly increases the yield of exosomes from an unlimited quantity
      of culture supernatants. Exosomes isolated by this technique are
      indistinguishable from exosomes recovered by direct ultracentrifugation. 

PMID- 24735773
TI  - In vivo analysis of the iris thickness by spectral domain optical coherence
      tomography.
AB  - PURPOSE: To assess the effectiveness of spectral domain optical coherence
      tomography (SD-OCT) in providing in vivo measurements of iris thickness in
      healthy and pathological subjects. METHODS: 14 healthy volunteers and 14 patients
      with unilateral Fuchs' uveitis were enrolled in the study. The two groups were
      comparable for age, gender and race. Each subject underwent complete clinical
      examination and anterior segment SD-OCT imaging in both eyes. SD-OCT scans of the
      iris were performed following a cross-sectional pattern. Iris thickness values
      were obtained using a purposely developed software-based analysis of OCT images.
      Measurements were carried out twice by two trained independent operators to
      assess intraobserver and interobserver repeatability. Analysis of iris thickness
      was conducted in four main quadrants: superior, inferior, nasal and temporal.
      Iris thickness values from normal subjects were compared with the ones measured
      in the affected and fellow eyes of patients with Fuchs' uveitis. RESULTS: Iris
      thickness measurements showed good intraobserver and interobserver repeatability
      (intraclass correlation coefficient >0.971). Superior and temporal iris sectors
      showed respectively thickest and thinnest values in all groups. In healthy eyes,
      iris thickness ranged from 327.92+/-37.29 MUm temporally to 405.25+/-48.49 MUm
      superiorly. Iris thickness measurements in the affected eyes of Fuchs' uveitis
      patients ranged from 285.48+/-56.02 MUm temporally to 376.12+/-60.97 MUm
      superiorly. Multiple comparison analysis showed iris thickness values to be
      significantly lower in eyes affected by Fuchs' uveitis than both in fellow eyes
      (p<0.001) of the same patients and in healthy eyes (p=0.0074). CONCLUSIONS: SD
      OCT is a suitable technique for iris thickness assessment. Thickness analysis
      must be carried out using a sectorial approach, taking into consideration
      anatomical variations existing between different iris regions. SD-OCT is a
      potentially useful tool for detecting iris thickness variations induced by
      pathological conditions such as Fuchs' uveitis.

PMID- 24735774
TI  - When case report became case series: 45 cases of late traumatic flap
      complications after laser-assisted in situ keratomileusis and review of Chinese
      literature.
AB  - OBJECTIVE: To report 45 cases of late traumatic flap complications after laser
      assisted in situ keratomileusis (LASIK) and discuss the continually increasing
      number of cases in China. METHODS: A multicentre retrospective survey of eye
      injuries was carried in 31 military hospitals from January 2006 to December 2011.
      Detailed information from the medical records of all 92 cases with a history of
      prior LASIK treatment were collected and summarised, with respect to visual
      acuity (VA), flap condition, treatment and final outcome. All Chinese
      publications relevant to late traumatic flap complications in Chinese patients
      were retrieved and summarised. RESULTS: 92 inpatients (92 eyes) underwent LASIK
      surgery; 45 of these had traumatic LASIK flap complications. Flap dislocation was
      the commonest and most needed surgical repair. VA after treatment was good and no
      statistically significant difference was observed when compared with the 47 cases
      without flap complications. 109 articles related to late traumatic flap
      complications after LASIK were retrieved from four Chinese document databases.
      There were 550 cases of late traumatic flap complications. From 2004, case
      reports became more common; 10 or more cases were reported in some case series.
      VA of most cases was good and there was no remarkable vision loss after
      treatment. CONCLUSIONS: Late traumatic flap complications after LASIK have become
      more frequent in China, although the prognosis of most cases is good.

PMID- 24735775
TI  - Health of the coral reefs at the US Navy Base, Guantanamo Bay, Cuba: a
      preliminary report based on isotopic records from gorgonians.
AB  - Specimens of the gorgonian Plexaura homomalla were sampled from several areas
      along the fringing reefs fronting the United States Naval Base at Guantanamo Bay,
      Cuba. Sample coverage extended from apparently healthy reefs in oceanic waters to
      declining reefs located in the plume of the drainage from upper parts of
      Guantanamo Bay. Tentacle tips were excised, and trunk sections were cut and
      polished. Stable isotope ratios of nitrogen (delta(15)N) and carbon indicate a
      strong correlation of reef health with proximity to the plume of the river. Of
      all the worldwide cases in which land-based sources of pollution have impacted
      reefs, this one may well be the most intractable. The US Navy has jurisdiction
      over the reefs, with the obligation to protect them, yet the threat comes down
      the river from Cuba. 

PMID- 24735776
TI  - An Analysis of Mass Casualty Incidents in the Setting of Mass Gatherings and
      Special Events.
AB  - OBJECTIVES: Mass gatherings (MGs) and special events typically involve large
      numbers of people in unfamiliar settings, potentially creating unpredictable
      situations. To assess the information available to guide emergency services and
      onsite medical teams in planning and preparing for potential mass casualty
      incidents (MCIs), we analyzed the literature for the past 30 years. METHODS: A
      search of the literature for MCIs at MGs from 1982 to 2012 was conducted and
      analyzed. RESULTS: Of the 290 MCIs included in this study, the most frequently
      reported mechanism of injury involved the movement of people under crowded
      conditions (162; 55.9%), followed by special hazards (eg, airplane crashes,
      pyrotechnic displays, car crashes, boat collisions: 57; 19.6%), structural
      failures (eg, building code violations, balcony collapses: 38; 13.1%), deliberate
      events (26; 9%), and toxic exposures (7; 2.4%). Incidents occurred in Asia (71;
      24%), Europe (69; 24%), Africa (48; 17%), North America (48; 27%), South America
      (27; 9%), the Middle East (25; 9%), and Australasia (2; 1%). A minimum of 12 877
      deaths and 27 184 injuries resulted. CONCLUSIONS: Based on our findings, we
      recommend that a centralized database be created. With this database, researchers
      can further develop evidence to guide prevention efforts and mitigate the effects
      of MCIs during MGs. (Disaster Med Public Health Preparedness. 2014;0:1-7).

PMID- 24735777
TI  - Genetic variation in niche construction and its implications: response to Shuker.

PMID- 24735778
TI  - Physical activity monitoring in patients with intermittent claudication.
AB  - OBJECTIVES: Reduced physical activity (PA) is associated with a higher mortality
      rate and more rapid functional decline in patients with intermittent claudication
      (IC). The newest generation of accelerometers can assess both direction and
      intensity of activities three-dimensionally and may also adequately calculate
      energy expenditure in daily life. The aim of this study was to quantify daily PA
      level and energy expenditure of newly diagnosed patients with IC and healthy
      controls. PA outcomes are compared with contemporary public health physical
      activity guidelines. METHODS: Before initiating treatment, 94 patients with newly
      diagnosed IC and 36 healthy controls were instructed to wear a tri-axial seismic
      accelerometer for 1 week. Daily PA levels (in metabolic equivalents, METs) were
      compared with the ACSM/AHA public health PA minimum recommendations (>=64
      METs.min.day, in bouts of >=10 minutes). A subgroup analysis assessed the effect
      of functional impairment on daily PA levels. RESULTS: Data from 56 IC patients
      and 27 healthy controls were available for analysis. Patients with IC
      demonstrated significantly lower mean daily PA levels (+/-SD) than controls (387
      +/- 198 METs.min vs. 500 +/- 156 METs.min, p = .02). This difference was solely
      attributable to a subgroup of IC patients with the largest functional impairment
      (WIQ-score < 0.4). Only 45% of IC patients met the public health physical
      activity guidelines compared with 74% of the healthy controls (p = .01).
      CONCLUSIONS: More than half of patients with IC do not meet recommended standards
      of PA. Considering the serious health risks associated with low PA levels, these
      findings underscore the need for more awareness to improve physical exercise in
      patients with IC.

PMID- 24735779
TI  - Ocular defects as surrogate end-points in trials comparing carotid endarterectomy
      and stenting.

PMID- 24735780
TI  - Crystal structures, spectra properties and DFT calculations studies on 4-phenyl-1
      (3-phenylallylidene)thiosemicarbazide and its Ni(II) complex.
AB  - 4-Phenyl-1-(3-phenylallylidene)thiosemicarbazide (HL) and its metal complex of
      NiL2 have been synthesized. For them, elemental analysis, IR and X-ray single
      crystal diffraction have been carried out. In complex NiL2, the central Ni(2+)
      ion coordinates with two deprotonated ligands of L(-) and adopts a distorted
      square planar configuration with the Ni(2+) ion being located at the inversion
      center. The thermal analyses result shows that complex NiL2 undergoes two
      decomposition processes. For the title compounds, DFT calculations of the
      structures and natural population analysis (NPA) have been performed at
      B3LYP/LANL2DZ level of theory. The predicted geometric parameters are compared
      with the experimental values and they are supported each other. By using TD-DFT
      method, electron spectra of ligand HL and complex NiL2 have been predicted, which
      suggest the B3LYP/LANL2DZ method can approximately simulate the electron spectra
      for the system presented here. The NPA results indicate that, for ligand HL, the
      electronic absorption spectra are mainly assigned to n-pi(*) and pi-pi(*)
      electron transitions, while for the complex NiL2, the electronic transitions are
      mainly derived from the contribution of an intra-ligand (IL) transition, a metal
      to-ligand charge transfer (MLCT) transition and a d-d transition. Based on
      vibrational analysis, thermodynamic properties for ligand HL and complex NiL2 at
      different temperatures have been obtained. 

PMID- 24735782
TI  - Individual differences in epistemic motivation and brain conflict monitoring
      activity.
AB  - It is well documented that motivation toward closure (NFC), defined as a desire
      for a quick and unambiguous answer to a question and an aversion to uncertainty,
      is linked to more structured, rigid, and persistent cognitive styles. However,
      the neurocognitive correlates of NFC have never been tested. Thus, using event
      related potentials, we examined the hypothesis that NFC is associated with the
      neurocognitive process for detecting discrepancies between response tendencies
      and higher level intentions. We found that greater NFC is associated with lower
      conflict-related anterior cingulate activity, suggesting lower sensitivity to
      cues for altering a habitual response pattern and lower sensitivity to committing
      errors. This study provides evidence that high NFC acts as a bulwark against
      anxiety-producing uncertainty and minimizes the experience of error.

PMID- 24735781
TI  - Allergic sensitization: food- and protein-related factors.
AB  - Presented here are emerging capabilities to precisely measure endogenous
      allergens in soybean and maize, consideration of food matrices on allergens, and
      proteolytic activity of allergens. Also examined are observations of global
      allergy surveys and the prevalence of food allergy across different locales.
      Allergenic potential is considered in the context of how allergens can be
      characterized for their biochemical features and the potential for proteins to
      initiate a specific immune response. Some of the limitations in performing
      allergen characterization studies are examined. A combination of physical traits
      of proteins, the molecular interaction between cells and proteins in the human
      body, and the uniqueness of human culture play a role in understanding and
      eventually predicting protein allergy potential. The impact of measuring food
      allergens on determining safety for novel food crops and existing allergenic
      foods was highlighted with the conclusion that measuring content without the
      context of clinically relevant thresholds adds little value to safety. These data
      and findings were presented at a 2012 international symposium in Prague organized
      by the Protein Allergenicity Technical Committee of the International Life
      Sciences Institute's Health and Environmental Sciences Institute. 

PMID- 24735783
TI  - Contributions of cellular and humoral immunity of Galleria mellonella larvae in
      defence against oral infection by Bacillus thuringiensis.
AB  - In this study the cellular and humoral immune reactions of the Greater wax moth
      Galleria mellonella have been investigated during bacterial infection caused by
      oral administration of Bacillus thuringiensis. Two different dose strengths were
      investigated to assess the contribution of immune parameters to induced Bt
      resistance. Low-dose (sublethal LC15) infection resulted in significantly
      elevated haemolymph phenoloxidase and lysozyme-like activity, enhanced phagocytic
      activity of haemocytes, and increased encapsulation responses in infected larvae
      at 48 and 72 h post infection. Higher doses of Bt (half-lethal LC50) also
      triggered significantly elevated haemolymph phenoloxidase and lysozyme-like
      activity, but decreased the coagulation index and activity of phenoloxidase in
      haemocytes of infected larvae. In both types of infection, the pool of
      circulating haemocytes became depleted. The importance of cellular and humoral
      immune reactions in induced insect resistance to intestinal bacterial infection
      Bt is herein discussed.

PMID- 24735784
TI  - A comparison of decision making in patients with bipolar i disorder and
      schizophrenia.

PMID- 24735785
TI  - MSARC: Multiple sequence alignment by residue clustering.
AB  - BACKGROUND: Progressive methods offer efficient and reasonably good solutions to
      the multiple sequence alignment problem. However, resulting alignments are biased
      by guide-trees, especially for relatively distant sequences. RESULTS: We propose
      MSARC, a new graph-clustering based algorithm that aligns sequence sets without
      guide-trees. Experiments on the BAliBASE dataset show that MSARC achieves
      alignment quality similar to the best progressive methods. Furthermore, MSARC
      outperforms them on sequence sets whose evolutionary distances are difficult to
      represent by a phylogenetic tree. These datasets are most exposed to the guide
      tree bias of alignments. AVAILABILITY: MSARC is available at
      http://bioputer.mimuw.edu.pl/msarc.

PMID- 24735786
TI  - Coexisting medical comorbidity and depression: multiplicative effects on health
      outcomes in older adults.
AB  - BACKGROUND: Depression in the elderly is often associated with coexisting medical
      illnesses. We investigated the individual and combined impacts of depression and
      medical illnesses on disability and quality of life among community-living older
      persons. METHODS: Cross-sectional and longitudinal analyses of data from 1,844
      participants aged 55 and above of the Singapore Longitudinal Aging Study (SLAS
      1). Baseline depressive symptoms (Geriatric Depressive Scale, GDS>=5) and chronic
      medical comorbidity (>=2) from self-reports were related to baseline and 2-year
      follow up instrumental and basic activities of daily living (IADL-BADL), and
      quality of life (Medical Outcomes Study 12-item Short Form (SF-12) physical
      component summary (PCS) and mental component summary (MCS) scores. RESULTS: The
      prevalence of depressive symptoms was 11.4%. In main effect analyses of cross
      sectional and longitudinal relationships, depression and medical comorbidity were
      individually associated with higher risk of IADL-BADL disability and lower PCS
      and MCS scores of quality of life, and only medical comorbidity was associated
      with increased risk of hospitalization. Significant interactive effects of
      depression and medical comorbidity were observed in longitudinal relationships
      with IADL-BADL disability (p = 0.03), PCS (p < 0.01), and MCS (p < 0.01) scores
      at follow up. The associations of medical comorbidity with increased odds of IADL
      BADL disability and decreased SF-12 PCS and MCS scores were at least threefolds
      stronger among depressed than nondepressed individuals. CONCLUSION: Medical
      comorbidities and depression exert additive and multiplicative effects on
      functional disability and quality of life. The adverse impact and potential
      treatment benefits of coexisting mental and physical conditions should be
      seriously considered in clinical practice.

PMID- 24735787
TI  - 'Practical' resources to support patient and family engagement in healthcare
      decisions: a scoping review.
AB  - BACKGROUND: Extensive literature exists on public involvement or engagement, but
      what actual tools or guides exist that are practical, tested and easy to use
      specifically for initiating and implementing patient and family engagement, is
      uncertain. No comprehensive review and synthesis of general international
      published or grey literature on this specific topic was found. A systematic
      scoping review of published and grey literature is, therefore, appropriate for
      searching through the vast general engagement literature to identify
      'patient/family engagement' tools and guides applicable in health organization
      decision-making, such as within Alberta Health Services in Alberta, Canada. This
      latter organization requested this search and review to inform the contents of a
      patient engagement resource kit for patients, providers and leaders. METHODS:
      Search terms related to 'patient engagement', tools, guides, education and
      infrastructure or resources, were applied to published literature databases and
      grey literature search engines. Grey literature also included United States,
      Australia and Europe where most known public engagement practices exist, and
      Canada as the location for this study. Inclusion and exclusion criteria were set,
      and include: English documents referencing 'patient engagement' with specific
      criteria, and published between 1995 and 2011. For document analysis and
      synthesis, document analysis worksheets were used by three reviewers for the
      selected 224 published and 193 grey literature documents. Inter-rater reliability
      was ensured for the final reviews and syntheses of 76 published and 193 grey
      documents. RESULTS: Seven key themes emerged from the literature synthesis
      analysis, and were identified for patient, provider and/or leader groups.
      Articles/items within each theme were clustered under main topic areas of
      'tools', 'education' and 'infrastructure'. The synthesis and findings in the
      literature include 15 different terms and definitions for 'patient engagement',
      17 different engagement models, numerous barriers and benefits, and 34 toolkits
      for various patient engagement and evaluation initiatives. CONCLUSIONS: Patient
      engagement is very complex. This scoping review for patient/family engagement
      tools and guides is a good start for a resource inventory and can guide the
      content development of a patient engagement resource kit to be used by
      patients/families, healthcare providers and administrators.

PMID- 24735788
TI  - Chromium-containing traditional Chinese medicine, Tianmai Xiaoke Tablet improves
      blood glucose through activating insulin-signaling pathway and inhibiting PTP1B
      and PCK2 in diabetic rats.
AB  - OBJECTIVE: Chromium is an essential mineral that is thought to be necessary for
      normal glucose homeostasis. Numerous studies give evidence that chromium
      picolinate can modulate blood glucose and insulin resistance. The main ingredient
      of Tianmai Xiaoke (TMXK) Tablet is chromium picolinate. In China, TMXK Tablet is
      used to treat type 2 diabetes. This study investigated the effect of TMXK on
      glucose metabolism in diabetic rats to explore possible underlying molecular
      mechanisms for its action. METHODS: Diabetes was induced in rats by feeding a
      high-fat diet and subcutaneously injection with a single dose of streptozotocin
      (50 mg/kg, tail vein). One week after streptozotocin-injection, model rats were
      divided into diabetic group, low dose of TMXK group and high dose of TMXK group.
      Eight normal rats were used as normal control. After 8 weeks of treatment,
      skeletal muscle was obtained and was analyzed using Roche NimbleGen mRNA array
      and quantitative polymerase chain reaction (qPCR). Fasting blood glucose, oral
      glucose tolerance test and homeostasis model assessment of insulin resistance
      (HOMA-IR) index were also measured. RESULTS: The authors found that the
      administration of TMXK Tablet can reduce the fasting blood glucose and fasting
      insulin level and HOMA-IR index. The authors also found that 2 223 genes from
      skeletal muscle of the high-dose TMXK group had significant changes in expression
      (1 752 increased, 471 decreased). Based on Kyoto encyclopedia of genes and
      genomes pathway analysis, the most three significant pathways were "insulin
      signaling pathway", "glycolysis/gluconeogenesis" and "citrate cycle (TCA)". qPCR
      showed that relative levels of forkhead box O3 (FoxO3), phosphoenolpyruvate
      carboxykinase 2 (Pck2), and protein tyrosine phosphatase 1B (Ptp1b) were
      significantly decreased in the high-dose TMXK group, while v-akt murine thymoma
      viral oncogene homolog 1 (Akt1) and insulin receptor substrate 2 (Irs2) were
      increased. CONCLUSION: Our data show that TMXK Tablet reduces fasting glucose
      level and improves insulin resistance in diabetic rats. The mechanism may be
      linked to the inactivation of PTP1B and PCK enzymes, or through intracellular
      pathways, such as the insulin signaling pathway.

PMID- 24735789
TI  - The use of complementary and alternative medicine by individuals with features of
      metabolic syndrome.
AB  - OBJECTIVE: To compare the use of complementary and alternative medicine (CAM),
      including dietary supplements, by individuals with and without features of
      metabolic syndrome (FeMS). METHODS: Using a cross sectional study design,
      information was obtained by self-administered questionnaires from 300 university
      individuals. FeMS was defined as any individuals self-reporting at least one of
      the clinical diagnoses of diabetes, hypertension, hyperlipidemia, or obesity.
      Finally, two categories were created for cross tabulation, and individuals with
      and without FeMS were compared. RESULTS: Of the 192 individuals completing the
      study, 39% (n=76) were currently using or had used CAM therapies in the past 12
      months. Individuals with FeMS (n=54, 28%) were more likely (P<0.05) to use
      different types of CAM therapies, in particular dietary and herbal supplements,
      aromatherapy and massage therapy compared to individuals without FeMS (n=138,
      72%). CONCLUSION: Individuals with FeMS were more likely to use CAM, particularly
      supplements. Doctors need to properly inquire about and understand their
      patients' supplement use, especially if CAM therapies are used in conjunction
      with conventional medications.

PMID- 24735791
TI  - Disaster Trauma: Federal Resources that Help Communities on Their Road to
      Recovery.
AB  - During the past several years, the US federal government has increased its role
      in preparing for and responding to natural and manmade disasters. The support and
      services that federal agencies provide to communities to address the
      psychological impact of trauma on citizens of all ages are valuable assets before
      and after a disaster. We used trauma theory to analyze disaster behavior health,
      assess the needs of at-risk populations, and identify the resources that the
      Department of Health and Human Services, Substance Abuse and Mental Health
      Services Administration, offers to the nation to assist communities in the
      psychological recovery process. (Disaster Med Public Health Preparedness.
      2014;x:1-5).

PMID- 24735790
TI  - Dr. Miriam Lee: a heroine for the start of acupuncture as a profession in the
      State of California.

PMID- 24735792
TI  - [The Cochrane Collaboration turns 20].

PMID- 24735793
TI  - Development and validation of a scoring system to identify individuals at high
      risk for advanced colorectal neoplasms who should undergo colonoscopy screening.

PMID- 24735794
TI  - Back to the beginning: restarting infliximab in inflammatory bowel disease
      patients with prior loss of response.

PMID- 24735795
TI  - The differential proliferative response of fetal and adult human skin fibroblasts
      to TGF-beta is retained when cultured in the presence of fibronectin or collagen.
AB  - BACKGROUND: Transforming growth factor-beta is a multifunctional and pleiotropic
      factor with decisive role in tissue repair. In this context, we have shown
      previously that TGF-beta inhibits the proliferation of fetal human skin
      fibroblasts but stimulates that of adult ones. Given the dynamic reciprocity
      between fibroblasts, growth factors and extracellular matrix (ECM) in tissue
      homeostasis, the present study aims to investigate the role of fibronectin and
      collagen in the proliferative effects of TGF-beta on fetal and adult cells.
      METHODS: Human fetal and adult skin fibroblasts were grown either on plastic
      surfaces or on surfaces coated with fibronectin or collagen type-I, as well as,
      on top or within three-dimensional matrices of polymerized collagen. Their
      proliferative response to TGF-beta was studied using tritiated thymidine
      incorporation, while the signaling pathways involved were investigated by Western
      analysis and using specific kinase inhibitors. RESULTS: Fetal skin fibroblast
      proliferation was inhibited by TGF-beta, while that of adult cells was stimulated
      by this factor, irrespective of the presence of fibronectin or collagen. Both
      inhibitory and stimulatory activities of TGF-beta on the proliferation of fetal
      and adult fibroblasts, respectively, were abrogated when the Smad pathway was
      blocked. Moreover, inhibition of fetal fibroblasts was mediated by PKA
      activation, while stimulation of adult ones was effected through the autocrine
      activation of FGF receptor and the MEK-ERK pathway. CONCLUSIONS: Fetal and adult
      human skin fibroblasts retain their differential proliferative response to TGF
      beta when cultured in the presence of fibronectin and unpolymerized or
      polymerized collagen. GENERAL SIGNIFICANCE: The interplay between TGF-beta and
      ECM supports the pleiotropic nature of this growth factor, in concordance with
      the different repair strategies between fetuses and adults. This article is part
      of a Special Issue entitled Matrix-mediated cell behaviour and properties.

PMID- 24735796
TI  - Cladosporol A, a new peroxisome proliferator-activated receptor gamma (PPARgamma)
      ligand, inhibits colorectal cancer cells proliferation through beta-catenin/TCF
      pathway inactivation.
AB  - BACKGROUND: Cladosporol A, a secondary metabolite from Cladosporium tenuissimum,
      exhibits antiproliferative properties in human colorectal cancer cells by
      modulating the expression of some cell cycle genes (p21(waf1/cip1), cyclin D1).
      METHODS: PPARgamma activation by cladosporol A was studied by overexpression and
      RNA interference assays. The interactions between PPARgamma and Sp1 were
      investigated by co-immunoprecipitation and ChIp assays. beta-Catenin subcellular
      distribution and beta-catenin/TCF pathway inactivation were analyzed by western
      blot and RTqPCR, respectively. Cladosporol A-induced beta-catenin proteasomal
      degradation was examined in the presence of the specific inhibitor MG132.
      RESULTS: Cladosporol A inhibits cell growth through upregulation of
      p21(waf1/cip1) gene expression mediated by Sp1-PPARgamma interaction. Exposure of
      HT-29 cells to cladosporol A causes beta-catenin nuclear export, proteasome
      degradation and reduced expression of its target genes. Upon treatment, PPARgamma
      also activates E-cadherin gene at the mRNA and protein levels. CONCLUSION: In
      this work we provide evidence that PPARgamma mediates the anti-proliferative
      action of cladosporol A in colorectal cancer cells. Upon ligand activation,
      PPARgamma interacts with Sp1 and stimulates p21(waf1/cip1) gene transcription.
      PPARgamma activation causes degradation of beta-catenin and inactivation of the
      downstream target pathway and, in addition, upregulates E-cadherin expression
      reinforcing cell-cell interactions and a differentiated phenotype. GENERAL
      SIGNIFICANCE: We elucidated the molecular mechanisms by which PPARgamma mediates
      the anticancer activity of cladosporol A.

PMID- 24735797
TI  - Time evolution of noise induced oxidation in outer hair cells: role of NAD(P)H
      and plasma membrane fluidity.
AB  - BACKGROUND: Noise exposure impairs outer hair cells (OHCs). The common basis for
      OHC dysfunction and loss by acoustic over-stimulation is represented by reactive
      oxygen species (ROS) overload that may affect the membrane structural
      organization through generation of lipid peroxidation. METHODS: Here we
      investigated in OHC different functional zones the mechanisms linking metabolic
      functional state (NAD(P)H intracellular distribution) to the generation of lipid
      peroxides and to the physical state of membranes by two photon fluorescence
      microscopy. RESULTS: In OHCs of control animals, a more oxidized NAD(P)H redox
      state is associated to a less fluid plasma membrane structure. Acoustic trauma
      induces a topologically differentiated NAD(P)H oxidation in OHC rows, which is
      damped between 1 and 6h. Peroxidation occurs after ~4h from noise insult, while
      ROS are produced in the first 0.2h and damage cells for a period of time after
      noise exposure has ended (~7.5h) when a decrease of fluidity of OHC plasma
      membrane occurs. OHCs belonging to inner rows, characterized by a lower metabolic
      activity with respect to other rows, show less severe metabolic impairment.
      CONCLUSIONS: Our data indicate that plasma membrane fluidity is related to
      NAD(P)H redox state and lipid peroxidation in hair cells. GENERAL SIGNIFICANCE:
      Our results could pave the way for therapeutic intervention targeting the onset
      of redox umbalance.

PMID- 24735798
TI  - Impact of subdomain D1 of the short form S1b of the human prolactin receptor on
      its inhibitory action on the function of the long form of the receptor induced by
      prolactin.
AB  - BACKGROUND: Long-form (LF) homodimers of the human prolactin receptor (PRLR)
      mediate prolactin's diverse actions. Short form S1b inhibits the LF function
      through heterodimerization. Reduced S1b/LF-ratio in breast cancer could
      contribute to tumor development/progression. Current work defines the structural
      and functional relevance of the D1 domain of S1b on its inhibitory function on
      prolactin-induced LF function. METHODS: Studies were conducted using mutagenesis,
      promoter/signaling analyses, bioluminescence resonance energy transfer (BRET) and
      molecular modeling approaches. RESULTS: Mutation of E69 in D1 S1b or adjacent
      residues at the receptor surface near to the binding pocket (S) causes loss of
      its inhibitory effect while mutations away from this region (A) or in the D2
      domain display inhibitory action as the wild-type. All S1b mutants preserved
      prolactin-induced Jak2 activation. BRET reveals an increased affinity in D1
      mutated S1b (S) homodimers in transfected cells stably expressing LF. In
      contrast, affinity in S1b homodimers with either D1 (A) or D2 mutations remained
      unchanged. This favors LF mediated signaling induced by prolactin. Molecular
      dynamics simulations show that mutations (S) elicit major conformational changes
      that propagate downward to the D1/D2 interface and change their relative
      orientation in the dimers. CONCLUSIONS: These findings demonstrate the essential
      role of D1 on the S1b structure and its inhibitory action on prolactin-induced LF
      mediated function. GENERAL SIGNIFICANCE: Major changes in receptor conformation
      and dimerization affinity are triggered by single mutations in critical regions
      of D1. Our structure-function/simulation studies provide a basis for modeling and
      design of small molecules to enhance inhibition of LF activation for potential
      use in breast cancer treatment.

PMID- 24735799
TI  - Bloody tears and recurrent nasolacrimal duct obstruction due to a retained
      silicone stent.
AB  - A 6-year-old girl with a history of bilateral nasolacrimal duct obstruction
      presented with recurrent tearing, discharge, and bloody tears from the right eye.
      The patient had a history of multiple prior probing and stenting procedures on
      the right nasolacrimal system. Endoscopic dacryocystorhinotomy revealed a
      retained portion of a prior stent and accompanying pyogenic granuloma, removal of
      which resolved her symptoms. 

PMID- 24735800
TI  - Botulinum toxin A in the treatment of pthiriasis palpebrarum.
AB  - Treatment of pthiriasis palpebrarum is usually difficult and prolonged, involving
      the use of anticholinesterase eye ointments, yellow oxide of mercury, or
      fluorescein. The most effective treatment, however, remains direct removal of all
      the lice and nits from the lashes. We report the use of topical application of
      botulinum toxin A in 6 children with pthiriasis palpebrum to facilitate complete
      removal. 

PMID- 24735801
TI  - French authorities raid drug company offices to investigate collusion over eye
      drug.

PMID- 24735802
TI  - Allergic sensitization: host-immune factors.
AB  - Allergic sensitization is the outcome of a complex interplay between the allergen
      and the host in a given environmental context. The first barrier encountered by
      an allergen on its way to sensitization is the mucosal epithelial layer. Allergic
      inflammatory diseases are accompanied by increased permeability of the
      epithelium, which is more susceptible to environmental triggers. Allergens and co
      factors from the environment interact with innate immune receptors, such as Toll
      like and protease-activated receptors on epithelial cells, stimulating them to
      produce cytokines that drive T-helper 2-like adaptive immunity in allergy-prone
      individuals. In this milieu, the next cells interacting with allergens are the
      dendritic cells lying just underneath the epithelium: plasmacytoid DCs, two types
      of conventional DCs (CD11b + and CD11b-), and monocyte-derived DCs. It is now
      becoming clear that CD11b+, cDCs, and moDCs are the inflammatory DCs that
      instruct naive T cells to become Th2 cells. The simple paradigm of non
      overlapping stable Th1 and Th2 subsets of T-helper cells is now rapidly being
      replaced by that of a more complex spectrum of different Th cells that together
      drive or control different aspects of allergic inflammation and display more
      plasticity in their cytokine profiles. At present, these include Th9, Th17, Th22,
      and Treg, in addition to Th1 and Th2. The spectrum of co-stimulatory signals
      coming from DCs determines which subset-characteristics will dominate. When IL-4
      and/or IL-13 play a dominant role, B cells switch to IgE-production, a process
      that is more effective at young age. IgE-producing plasma cells have been shown
      to be long-lived, hiding in the bone-marrow or inflammatory tissues where they
      cannot easily be targeted by therapeutic intervention. Allergic sensitization is
      a complex interplay between the allergen in its environmental context and the
      tendency of the host's innate and adaptive immune cells to be skewed towards
      allergic inflammation. These data and findings were presented at a 2012
      international symposium in Prague organized by the Protein Allergenicity
      Technical Committee of the International Life Sciences Institute's Health and
      Environmental Sciences Institute. 

PMID- 24735803
TI  - Need fulfillment, need importance, and depressive symptoms of residents over the
      first eight months of living in a nursing home.
AB  - BACKGROUND: Based on self-determination theory and adaptation theories, the study
      aim was to investigate the relationship between need fulfillment (of autonomy,
      relatedness, and competence), need importance, and depressive symptoms during the
      first months of living in a nursing home. METHODS: Eight-month longitudinal
      questionnaire study in which 75 persons newly admitted to units for physically
      frail residents participated at baseline. Twenty-three longitudinal participants
      were remaining at the third and final measurement wave. RESULTS: The results show
      a main effect of need fulfillment and an interaction effect of need fulfillment
      and need importance on depressive symptoms over time. A prototypical plot shows
      that residents with low need fulfillment had higher initial levels of depressive
      symptoms that decreased modestly over time, regardless of their need importance.
      Residents with high need fulfillment had lower initial levels of depressive
      symptoms, but their trajectories differed for participants with low and high need
      importance. Residents with low need importance started with lower levels of
      depressive symptoms but remained stable over time, whereas residents with high
      need importance had more depressive symptoms at T1 that decreased slightly over
      time. CONCLUSIONS: In general, depressive symptoms do not change over time.
      However, individual trajectories of depressive symptoms seem to depend on
      individual need fulfillment and need importance. The residents that consider need
      fulfillment to be highly important but experience low need fulfillment had higher
      initial levels of depressive symptoms that decreased modestly over time, although
      the level of depressive symptoms remained higher as compared to the other
      residents.

PMID- 24735804
TI  - Maternal gestational weight gain and offspring risk for childhood overweight or
      obesity.
AB  - OBJECTIVE: The objective of the study was to evaluate the association between
      gestational weight gain, per the 2009 Institute of Medicine (IOM)
      recommendations, and offspring overweight/obesity at 2-5 years of age. STUDY
      DESIGN: This was a prospective cohort study of 4145 women who completed a health
      survey (2007-2009) and subsequently delivered a singleton at Kaiser Permanente
      Northern California (2007-2010). Childhood overweight/obesity was defined as a
      body mass index (BMI) z-score of the 85th percentile or greater of the Centers
      for Disease Control and Prevention child growth standards. Gestational weight
      gain was categorized according to the 2009 IOM recommendations. Logistic
      regression was used; meeting the IOM recommendations was the referent. RESULTS:
      Exceeding the IOM recommendations was associated with a 46% increase in odds of
      having an overweight/obese child (odds ratio [OR], 1.46; 95% confidence interval
      [CI], 1.17-1.83), after adjusting for maternal prepregnancy BMI, race/ethnicity,
      age at delivery, education, child age, birthweight, gestational age at delivery,
      gestational diabetes, parity, infant sex, total metabolic equivalents, and
      dietary pattern. The OR (95% CI) for childhood overweight/obesity among women
      gaining below the IOM recommendations was 1.23 (0.88-1.71). The associations
      between gaining outside the IOM recommendations and childhood obesity were
      stronger among women with a normal prepregnancy BMI (OR, 1.63; 95% CI, 1.03-2.57)
      (below); OR, 1.79; 95% CI, 1.32-2.43) (exceeded). CONCLUSION: Gestational weight
      gain outside the IOM recommendations is associated with increased odds of
      childhood overweight/obesity, independent of several potential confounders and
      mediators. Gestational weight gain had a greater impact on childhood
      overweight/obesity among normal-weight women, suggesting that the effect may be
      independent of genetic predictors of obesity.

PMID- 24735805
TI  - Is metal nanofluid reliable as heat carrier?
AB  - A pre- and post experimental analysis of copper-water and silver-water nanofluids
      are conducted to investigate minimal changes in quality of nanofluids before and
      after an effective heat transfer. A single loop oscillating heat pipe (OHP)
      having inner diameter of 2.4mm is charged with aforementioned nanofluids at 60%
      filling ratio for end to end heat transfer. Post experimental analysis of both
      nanofluids raises questions to the physical, chemical and thermal stability of
      such suspension for hazardless uses in the field of heat transfer. The color,
      deposition, dispersibility, propensity to be oxidized, disintegration,
      agglomeration and thermal conductivity of metal nanofluids are found to be
      strictly affected by heat transfer process and vice versa. Such degradation in
      quality of basic properties of metal nanofluids implies its challenges in
      practical application even for short-term heat transfer operations at oxidative
      environment as nano-sized metal particles are chemically more unstable than its
      bulk material. The use of the solid/liquid suspension containing metal
      nanoparticles in any heat exchanger as heat carrier might be detrimental to the
      whole system. 

PMID- 24735806
TI  - A phase II/III trial of bitopertin monotherapy compared with placebo in patients
      with an acute exacerbation of schizophrenia - results from the CandleLyte study.
AB  - Bitopertin is a glycine reuptake inhibitor postulated to improve N-methyl-d
      aspartate receptor hypofunction by increasing synaptic glycine concentrations.
      This randomised, double-blind, placebo- and active-controlled phase II/III trial
      evaluated the efficacy and safety of bitopertin monotherapy over 4 weeks in
      patients with acute exacerbation of schizophrenia. Of 301 patients randomised,
      299 received placebo (n=80), bitopertin 10mg (n=80) or 30mg (n=77), or olanzapine
      15mg (n=62). The primary endpoint, change from baseline in mean Positive and
      Negative Syndrome Scale (PANSS) total score, showed non-statistically significant
      improvements with bitopertin 30mg and olanzapine vs. placebo: bitopertin 10mg (
      11.7; standard error [SE], 1.89; p=0.945), bitopertin 30mg (-15.3; SE, 1.87;
      p=0.211), olanzapine (-14.9; SE, 2.13; p=0.295) and placebo (-11.9; SE, 1.90).
      The PANSS positive subscale score, a secondary endpoint, also showed improvement
      with bitopertin 30mg (p=0.030) whereas a trend was observed with olanzapine
      (p=0.072) vs. placebo. Although not statistically significant, bitopertin 30mg
      and olanzapine reduced overall illness severity (Clinical Global Impression
      Severity Scale; p=0.098 and p=0.126, respectively). More patients receiving
      bitopertin 30mg (51.3%) or olanzapine (52.5%) than placebo (32.9%) were ready for
      hospital discharge at Week 4 (bitopertin, p=0.014; olanzapine, p=0.024). In
      summary, this study failed due to lack of statistical separation of either
      bitopertin or olanzapine (active control) from placebo on the primary endpoint.
      Of interest, improved positive symptoms and readiness for hospital discharge were
      associated with both bitopertin and olanzapine treatment. Bitopertin was safe and
      well tolerated in this study. 

PMID- 24735807
TI  - [Resuscitation for myocardial infarction and head injury: first the heart or
      first the head?].
AB  - Loss of circulation in a patient results in collapse and therefore possible head
      injury. After percutaneous coronary intervention (PCI) including anticoagulation,
      comatose patients are sedated for mild therapeutic hypothermia. Recognised or
      unrecognised head trauma may have dramatic clinical consequences. A 42-year-old
      male with unrecognised head trauma died due to a massive intracranial haemorrhage
      (ICH) during the hypothermia phase after being treated with PCI. A 76-year-old
      female, on anticoagulation for atrial fibrillation, with recognised ICH which
      resulted in an adjusted PCI, died after five days due to a lethal re-bleed. In a
      55-year-old male with neurological abnormalities after mild head trauma, the PCI
      was postponed for a (negative) head CT which might have increased cardiac muscle
      damage. Nowadays more patients reach hospital after being resuscitated for
      cardiac arrest and possible head trauma should be considered in all these
      patients. This could lead to adjustments being made in the treatment protocol. 

PMID- 24735808
TI  - [Treatment of abdominal aortic aneurysm: is there still a place for open
      repair?].
AB  - Due to lower peri-operative mortality, lower risk of complications and shorter
      duration of hospital stay, endovascular aneurysm repair has become preferential
      treatment for an infrarenal aortic aneurysm. Three randomised studies that
      compared endovascular repair with open repair now report follow-up data of an
      average of six years. The data shows a loss of peri-operative mortality advantage
      after two to three years. More re-interventions are performed following
      endovascular treatment. The predominant cause of death is due to cardiovascular
      events, for which optimal medical therapy is crucial. The initial mortality
      advantage of endovascular aneurysm repair compared to open repair is lost sooner
      in elderly and high-risk patients than in those patients who are relatively young
      and low-risk.

PMID- 24735809
TI  - [Hyponatraemia].
AB  - Because hyponatraemia can be caused by many disorders, the diagnostic approach to
      hyponatraemia can be challenging for physicians. Causes of hyponatraemia can be
      classified according to a combination of laboratory parameters (e.g. sodium
      levels and osmolality in serum and urine) and clinical parameters (e.g. volume
      status, medication). Based on the description of two patient cases, the
      differential diagnosis of hyponatraemia is discussed by combining these
      parameters. 

PMID- 24735810
TI  - [Vaginal delivery safe for twins starting at 32 weeks?].
AB  - Compared with other countries, the elective caesarean section rate for twins is
      relatively low in the Netherlands. Worldwide, there is an increasing trend toward
      performing more elective caesarean sections for women with a twin pregnancy at
      term, be it for twins with the first child in breech or in cephalic presentation.
      The results of the 'Twin Birth Study' indicate that a planned caesarean section
      does not improve outcome as compared with planned vaginal birth for twins with
      the first child in cephalic position beyond 32 weeks gestation. During the study,
      an experienced obstetrician was present during planned vaginal delivery and there
      was a possibility of performing a secondary caesarean section within 30 minutes.
      This study provides an additional argument to guarantee the aforementioned
      conditions in all hospitals where women plan to deliver their twins vaginally.
      However, the definition of an experienced obstetrician is subject to debate. 

PMID- 24735811
TI  - [Brain metastases occurring more often in colorectal carcinoma].
AB  - BACKGROUND: Colorectal carcinoma (CRC) has a high incidence. If metastatic
      disease develops, the liver and lungs are the most frequently involved sites.
      Brain metastases are rare. CASE DESCRIPTION: We present a male patient (70 years
      old) with lung and liver metastases of CRC. For many years the disease was in
      good remission with palliative chemotherapy. He developed very acute neck pain
      and later also vomiting. The latter turned out to be based on the presence of
      brain metastases, which was soon fatal. CONCLUSION: The incidence of CRC is
      rising and with it the incidence of symptomatic brain metastases in CRC. Due to
      the development of more effective systemic chemotherapy, survival of advanced CRC
      has improved, providing more time for symptomatic brain metastases to develop.

PMID- 24735812
TI  - [A boy with a wart-like lesion of the toe].
AB  - A 10-year-old boy consulted a dermatologist with a painful, subungual tumour on
      one of his toes. X-ray showed an outgrowth of the distal phalanx and
      histopathological investigation showed osteochondromatous proliferation. The
      patient was diagnosed with exostosis. Subungual exostoses are benign
      osteocartilaginous tumours that occur beneath the nail bed. Excision was
      performed, the patient recovered well. 

PMID- 24735813
TI  - [The price of healthy nutrition].
AB  - Governments can influence healthy dietary choices of populations by taxing
      relatively unhealthy foods and drinks and/or subsidizing relatively healthy
      options. Experimental and modelling studies have shown that such fiscal policies
      can contribute to the prevention of diseases such as obesity. 

PMID- 24735814
TI  - Mean platelet volume: a novel predictive marker for mortality in patients with
      acute mesenteric ischemia?

PMID- 24735815
TI  - Geniposide suppresses LPS-induced nitric oxide, PGE2 and inflammatory cytokine by
      downregulating NF-kappaB, MAPK and AP-1 signaling pathways in macrophages.
AB  - Inflammatory responses are important to host immune reactions, but uncontrolled
      inflammatory mediators may aid in the pathogenesis of other inflammatory
      diseases. Geniposide, an iridoid glycoside found in the herb gardenia, is
      believed to have broad-spectrum anti-inflammatory effects in murine models but
      its mechanism of action is unclear. We investigated the action of this compound
      in murine macrophages stimulated by lipopolysaccharide (LPS), as the stimulation
      of macrophages by LPS is known to induce inflammatory reactions. We determined
      the effect of geniposide on LPS-induced production of the inflammatory mediators,
      nitric oxide (NO) and prostaglandin E2 (PGE2), the mRNA and protein expression of
      the NO and PGE2 synthases, inducible nitric oxide synthase (iNOS) and
      cyclooxygenase-2 (COX-2), respectively, and the mRNA and protein expression of
      the inflammatory cytokine, tumor necrosis factor-alpha (TNF-alpha) and
      interleukin-6 (IL-6). Furthermore, nuclear factor (NF)-kappaB, mitogen-activated
      protein kinase (MAPK) and activator protein (AP)-1 activity were assayed. To
      understand the action of geniposide on the NF-kappaB and MAPK pathways, we
      studied the effect of NF-kappaB and MAPK inhibitors on the LPS-induced production
      of NO, PGE2 and TNF-alpha. Our findings clearly showed that geniposide mainly
      exerts its anti-inflammatory effects by inhibiting the LPS-induced NF-kappaB,
      MAPK and AP-1 signaling pathways in macrophages, which subsequently reduces
      overexpression of the inducible enzymes iNOS and COX-2 and suppresses the
      expression and release of the inflammatory factors, TNF-alpha, IL-6, NO and PGE2.
      Thus, geniposide shows promise as a therapeutic agent in inflammatory diseases. 

PMID- 24735816
TI  - Tryptase inhibitor APC 366 prevents hepatic fibrosis by inhibiting collagen
      synthesis induced by tryptase/protease-activated receptor 2 interactions in
      hepatic stellate cells.
AB  - Protease-activated receptor (PAR) 2 is a G-protein-coupled receptor that is
      activated by mast cell tryptase. PAR-2 activation augments profibrotic pathways
      through the induction of extracellular matrix proteins. PAR-2 is widely expressed
      in hepatic stellate cells (HSCs), but the role of tryptase/PAR-2 interaction in
      liver fibrosis is unclear. We studied the development of bile duct ligation (BDL)
      induced hepatic fibrosis in rats treated with mast cell tryptase inhibitor APC
      366, and showed that APC 366 reduced hepatic fibrosis scores, collagen content
      and serum biochemical parameters. Reduced fibrosis was associated with decreased
      expression of PAR-2 and alpha-smooth muscle actin (alpha-SMA). Our findings
      demonstrate that mast cell tryptase induces PAR-2 activation to augment HSC
      proliferation and promote hepatic fibrosis in rats. Treatment with tryptase
      antagonists may be a novel therapeutic approach to prevent fibrosis in patients
      with chronic liver disease. 

PMID- 24735817
TI  - Aptamers targeting rabies virus-infected cells inhibit street rabies virus in
      vivo.
AB  - Rabies is a viral infection of the CNS that is almost always fatal once symptoms
      occur. No effective treatment of the disease is available and novel antiviral
      strategies are urgently required. Street rabies viruses are field isolates known
      to be highly neurotropic. Aptamers are single-stranded oligonucleotides that bind
      their targets with high affinity and specificity and thus have potential for use
      in diagnostic and therapeutic applications. In this study, we demonstrate that
      the aptamers FO24 and FO21, which target RABV-infected cells, can significantly
      protect mice from a lethal dose of the street rabies virus FJ strain in vivo.
      Groups receiving preexposure prophylaxis had higher survival rates than the
      groups receiving postexposure prophylaxis. When mice were inoculated with
      aptamers (4 nmol) for 24h by intracranial or intramuscular injection prior to
      intramuscular inoculation with the FJ strain, approximately 60% of the mice
      survived. These results indicate that the FO21 and FO24 aptamers may be used to
      develop preventative antiviral therapy against rabies disease.

PMID- 24735818
TI  - Saturation sampling for spatial variation in multiple air pollutants across an
      inversion-prone metropolitan area of complex terrain.
AB  - BACKGROUND: Characterizing intra-urban variation in air quality is important for
      epidemiological investigation of health outcomes and disparities. To date,
      however, few studies have been designed to capture spatial variation during
      select hours of the day, or to examine the roles of meteorology and complex
      terrain in shaping intra-urban exposure gradients. METHODS: We designed a spatial
      saturation monitoring study to target local air pollution sources, and to
      understand the role of topography and temperature inversions on fine-scale
      pollution variation by systematically allocating sampling locations across
      gradients in key local emissions sources (vehicle traffic, industrial facilities)
      and topography (elevation) in the Pittsburgh area. Street-level integrated
      samples of fine particulate matter (PM2.5), black carbon (BC), nitrogen dioxide
      (NO2), sulfur dioxide (SO2), and ozone (O3) were collected during morning rush
      and probable inversion hours (6-11 AM), during summer and winter. We hypothesized
      that pollution concentrations would be: 1) higher under inversion conditions, 2)
      exacerbated in lower-elevation areas, and 3) vary by season. RESULTS: During July
      - August 2011 and January - March 2012, we observed wide spatial and seasonal
      variability in pollution concentrations, exceeding the range measured at
      regulatory monitors. We identified elevated concentrations of multiple pollutants
      at lower-elevation sites, and a positive association between inversion frequency
      and NO2 concentration. We examined temporal adjustment methods for deriving
      seasonal concentration estimates, and found that the appropriate reference
      temporal trend differs between pollutants. CONCLUSIONS: Our time-stratified
      spatial saturation approach found some evidence for modification of inversion
      concentration relationships by topography, and provided useful insights for
      refining and interpreting GIS-based pollution source indicators for Land Use
      Regression modeling.

PMID- 24735819
TI  - Insulin resistance and gray matter volume in neurodegenerative disease.
AB  - The goal of this study was to compare insulin resistance in aging and aging
      related neurodegenerative diseases, and to determine the relationship between
      insulin resistance and gray matter volume (GMV) in each cohort using an unbiased,
      voxel-based approach. Insulin resistance was estimated in apparently healthy
      elderly control (HC, n=21) and neurodegenerative disease (Alzheimer's disease
      (AD), n=20; Parkinson's disease (PD), n=22) groups using Homeostasis Model
      Assessment of Insulin Resistance 2 (HOMA2) and intravenous glucose tolerance test
      (IVGTT). HOMA2 and GMV were assessed within groups through General Linear Model
      multiple regression. We found that HOMA2 was increased in both AD and PD compared
      to the HC group (HC vs. AD, p=0.002, HC vs. PD, p=0.003), although only AD
      subjects exhibited increased fasting glucose (p=0.005). Furthermore, our voxel
      based morphometry analysis revealed that HOMA2 was related to GMV in all cohorts
      in a region-specific manner (p<0.001, uncorrected). Significant relationships
      were observed in the medial prefrontal cortex (HC), medial temporal regions (AD),
      and parietal regions (PD). Finally, the directionality of the relationship
      between HOMA2 and GMV was disease-specific. Both HC and AD subjects exhibited
      negative relationships between HOMA2 and brain volume (increased HOMA2 associated
      with decreased brain volume), while a positive relationship was observed in PD.
      This cross-sectional study suggests that insulin resistance is increased in
      neurodegenerative disease, and that individuals with AD appear to have more
      severe metabolic dysfunction than individuals with PD or PD dementia. 

PMID- 24735822
TI  - Risk Communication Recommendations and Implementation During Emerging Infectious
      Diseases: A Case Study of the 2009 H1N1 Influenza Pandemic.
AB  - OBJECTIVE: To examine their implementation, we analyzed World Health Organization
      (WHO) and Centers for Disease Control and Prevention (CDC) guidelines from 2005
      to 2008 for risk communication during an emerging infectious disease outbreak,
      WHO and CDC reports on implementing the guidelines worldwide after the 2009 H1N1
      pandemic; and a case study of a member state. METHODS: A qualitative study
      compared WHO and CDC guidelines from 2005 to 2008 with WHO and CDC reports from
      2009 to 2011, documenting their implementation during the H1N1 outbreak and
      assessed how these guidelines were implemented, based on the reports and Israeli
      stakeholders (n=70). RESULTS: Eight risk communication subthemes were identified:
      trust, empowerment, uncertainty, communicating the vaccine, inclusion,
      identification of subpopulations and at-risk groups, segmentation, and 2-way
      communication. The reports and case study disclosed a gap between international
      guidelines and their local-level implementation. The guidelines were mostly top
      down communications, with little consideration for individual member-state
      implementation. The WHO and CDC recommendations were not always based on
      formative evaluation studies, which undermined their validity. CONCLUSIONS: In
      formulating effective communication strategies, the first step is to define the
      goal of a vaccination program. We recommend implementing conceptual elements from
      the most current theoretical literature when planning communication strategies
      and increasing organizational involvement in implementing guidelines in future
      health crises. (Disaster Med Public Health Preparedness. 2014;x:1-12).

PMID- 24735821
TI  - Prenatal betamethasone does not affect glutamatergic or GABAergic neurogenesis in
      preterm newborns.
AB  - Prenatal glucocorticoids (GCs) are routinely used for pregnant women in preterm
      labor to prevent respiratory distress syndrome and intraventricular hemorrhage in
      premature infants. However, the effect of antenatal GCs on neurogenesis in
      preterm neonates remains elusive. Herein, we hypothesized that prenatal GCs might
      suppress both glutamatergic and GABAergic neurogenesis in preterm rabbits and
      that this treatment would induce distinct changes in the expression of
      transcription factors regulating these developmental events. To test our
      hypotheses, we treated pregnant rabbits with betamethasone at E27 and E28,
      delivered the pups at E29 (term=32d), and assessed neurogenesis at birth and
      postnatal day 3. We quantified radial glia (Sox2(+)) and intermediate progenitor
      cells (Tbr2(+)) in the dorsal cortical subventricular zone to assess
      glutamatergic neuronal progenitors, and counted Nkx2.1(+) and Dlx2(+) cells in
      the ganglionic eminence to evaluate GABAergic neurogenesis. In addition, we
      assayed transcription factors regulating neurogenesis. We found that prenatal GCs
      did not affect the densities of radial glia and intermediate progenitors of
      glutamatergic or GABAergic neurons. The number of GABA(+) interneurons in the
      ganglionic eminence was similar between the prenatal GC-treated pups compared to
      untreated controls. Moreover, the mRNA expression of transcription factors,
      including Pax6, Ngn1/2, Emx1/2, Insm1, Dlx1, Nkx2.1, and Gsh2, were comparable
      between the two groups. However, there was a transient elevation in Mash1 protein
      in betamethasone-treated pups relative to controls at birth. These data suggest
      that prenatal GC treatment does not significantly impact the balance of
      glutamatergic and GABAergic neurogenesis in premature infants.

PMID- 24735823
TI  - Bisbenzylisoquinoline and hasubanane alkaloids from Stephania abyssinica (Dillon
      & A. Rich) (Menispermeceae).
AB  - Two bisbenzylisoquinoline and one hasubanane alkaloids: (-)-pseudocurine (1), (-)
      pseudoisocurine (2) and (-)-10-oxoaknadinine (3), were isolated from leaf extract
      of Stephania abyssinica, a plant used in traditional medicine in South Nyanza
      region of Kenya. They were characterized using 1D ((1)H, (13)C and DEPT) and 2D
      (COSY, NOESY, HMQC and HMBC) NMR techniques. (-)-Pseudocurine (1) and (-)
      pseudoisocurine (2) exhibited strong to moderate anti-plasmodial activity while (
      )-10-oxoaknadinine (3) showed moderate to mild activity. 

PMID- 24735824
TI  - Biofilm blocking sesquiterpenes from Teucrium polium.
AB  - The chemical composition and antibacterial activity of Teucrium polium L.
      (Lamiaceae) were assessed; sixteen compounds were isolated from a CH2Cl2/MeOH
      extract of the aerial parts of the plant including four sesquiterpenes
      4beta,5alpha-epoxy-7alphaH-germacr-10(14)-en-6beta-ol-1-one, 4beta,5alpha-epoxy
      7alphaH-germacr-10(14)-en,1beta-hydroperoxyl,6beta-ol, 4beta,5beta-epoxy-7alphaH
      germacr-10(14)-en,1beta-hydroperoxyl,6beta-ol and 4alpha,5beta-epoxy-7alphaH
      germacr-10(14)-en,1beta-hydroperoxyl,6alpha-ol, together with seven known
      sesquiterpenes, one known iridoid glycoside, two known flavonoids, and one known
      phenylpropanoid glycoside. Structures were elucidated on the basis of
      spectroscopic (UV, (1)H and (13)C NMR) data, as well as two-dimensional NMR ((1)H
      (1)H COSY, HMQC, NOESY and HMBC), and ESI-MS analysis. The relative
      stereochemistry of the ketone was established by X-ray crystallography, while its
      absolute configuration was attained by a modified Mosher's method. Antibacterial
      activity of the crude extract, as well as with four of the isolated metabolites,
      was observed with Staphylococcus aureus anti-biofilm activity in the low MUMol
      range. Diverse sesquiterpene-skeleton structure and corresponding comprehensive
      enzyme capacity is discussed. 

PMID- 24735825
TI  - Nitrogen supply affects anthocyanin biosynthetic and regulatory genes in
      grapevine cv. Cabernet-Sauvignon berries.
AB  - Accumulation of anthocyanins in grape berries is influenced by environmental
      factors (such as temperature and light) and supply of nutrients, i.e., fluxes of
      carbon and nitrogen feeding the berry cells. It is established that low nitrogen
      supply stimulates anthocyanin production in berry skin cells of red varieties.
      The present works aims to gain a better understanding of the molecular mechanisms
      involved in the response of anthocyanin accumulation to nitrogen supply in
      berries from field grown-plants. To this end, we developed an integrated approach
      combining monitoring of plant nitrogen status, metabolite measurements and
      transcript analysis. Grapevines (cv. Cabernet-Sauvignon) were cultivated in a
      vineyard with three nitrogen fertilization levels (0, 60 and 120 kg ha(-1) of
      nitrogen applied on the soil). Anthocyanin profiles were analyzed and compared
      with gene expression levels. Low nitrogen supply caused a significant increase in
      anthocyanin levels at two ripening stages (26 days post-veraison and maturity).
      Delphinidin and petunidin derivatives were the most affected compounds.
      Transcript levels of both structural and regulatory genes involved in anthocyanin
      synthesis confirmed the stimulation of the phenylpropanoid pathway. Genes
      encoding phenylalanine ammonia-lyase (PAL), chalcone synthase (CHS), flavonoid
      3',5'-hydroxylase (F3'5'H), dihydroflavonol-4-reductase (DFR), leucoanthocyanidin
      dioxygenase (LDOX) exhibited higher transcript levels in berries from plant
      cultivated without nitrogen compared to the ones cultivated with 120 kg ha(-1)
      nitrogen fertilization. The results indicate that nitrogen controls a coordinated
      regulation of both positive (MYB transcription factors) and negative (LBD
      proteins) regulators of the flavonoid pathway in grapevine.

PMID- 24735826
TI  - Wounding stress causes rapid increase in concentration of the naturally occurring
      2',3'-isomers of cyclic guanosine- and cyclic adenosine monophosphate (cGMP and
      cAMP) in plant tissues.
AB  - 3',5'-Cyclic guanosine monophosphate (cGMP) and 3',5'-cyclic adenosine
      monophosphate (cAMP) are well reported second messenger molecules involved in
      cellular signal transduction, in physiological functions such as
      neurotransmission in animals and in the modulation of cell growth and
      differentiation. In plants, 3',5'-cyclic nucleotides have been implicated in the
      regulation of ion homeostasis, hormone and stress responses. The behavior of the
      2',3'-cyclic nucleotide variants is also known in animal tissue but no
      quantitative information is available about 2',3'-cAMP and 2',3'-cGMP in plant
      material. A recently developed HILIC-SPE/LC-MS/MS method for the analysis of
      cyclic nucleotides in blood and animal tissue was therefore adapted to measure
      2',3'-cAMP and 2',3'-cGMP concentrations in plant material. Cyclic nucleotide
      concentrations were measured in Arabidopsis thaliana (Col-0) leaves before and
      after the application of wounding stress. A significant (~5-fold) up-regulation
      of 2',3'-cAMP and 2',3'-cGMP was measured in Arabidopsis leaves compared to the
      control samples. The results indicate a thus far unreported strong correlation
      between plant stress and both 2',3'-cAMP and 2',3'-cGMP levels in plant material,
      and may open new avenues towards understanding the role of cyclic nucleotides in
      plants. 

PMID- 24735827
TI  - Isolation and characterization of six labdane diterpenes and one pregnane steroid
      of Turraeanthus africanus.
AB  - Six labdane diterpene derivatives, named turraeanins F-J (3-6, 8) and epi
      turraeanin J (7), and a pregnane steroid derivative named turraeasterodionene
      (2), were isolated by preparative high performance liquid chromatography together
      with thirteen known compounds from the Cameroonian medicinal plant Turraeanthus
      africanus. Their structures were elucidated by means of nuclear magnetic
      resonance spectroscopy and high-resolution mass spectrometry in conjunction with
      the published data for the analogs, as well as the fragmentation patterns of each
      compound. Most of the known compounds were obtained for the first time from this
      plant. The compounds (2-7) were tested for their antibacterial efficacies against
      both Gram-positive and Gram-negative bacteria, including some clinically
      important Risk group 2 human pathogens. Compound 4 exhibited the most pronounced
      antibacterial effectiveness comparable to standard reference streptomycin, with
      more potency against Gram-positive than Gram-negative bacteria. By comparing
      compounds 3, 4 and 5, a tentative structure-activity relationship could be drawn;
      selected oxidations at C-16 and C-18 drastically reduced the antibacterial
      efficacy of the parent compound (4). These results revealed the potential of
      compound 4 as a suitable antibacterial lead compound that might be used for
      further development of other derivatives to increase the antimicrobial efficacy. 

PMID- 24735820
TI  - An update on the connections of the ventral mesencephalic dopaminergic complex.
AB  - This review covers the intrinsic organization and afferent and efferent
      connections of the midbrain dopaminergic complex, comprising the substantia
      nigra, ventral tegmental area and retrorubral field, which house, respectively,
      the A9, A10 and A8 groups of nigrostriatal, mesolimbic and mesocortical
      dopaminergic neurons. In addition, A10dc (dorsal, caudal) and A10rv
      (rostroventral) extensions into, respectively, the ventrolateral periaqueductal
      gray and supramammillary nucleus are discussed. Associated intrinsic and
      extrinsic connections of the midbrain dopaminergic complex that utilize gamma
      aminobutyric acid (GABA), glutamate and neuropeptides and various co-expressed
      combinations of these compounds are considered in conjunction with the dopamine
      containing systems. A framework is provided for understanding the organization of
      massive afferent systems descending and ascending to the midbrain dopaminergic
      complex from the telencephalon and brainstem, respectively. Within the context of
      this framework, the basal ganglia direct and indirect output pathways are treated
      in some detail. Findings from rodent brain are briefly compared with those from
      primates, including humans. Recent literature is emphasized, including
      traditional experimental neuroanatomical and modern gene transfer and optogenetic
      studies. An attempt was made to provide sufficient background and cite a
      representative sampling of earlier primary papers and reviews so that people new
      to the field may find this to be a relatively comprehensive treatment of the
      subject. 

PMID- 24735828
TI  - S-nitrosylation of TRIM72 mends the broken heart: a molecular modifier-mediated
      cardioprotection.

PMID- 24735829
TI  - Transcriptome profiling reveals that the SM22alpha-regulated molecular pathways
      contribute to vascular pathology.
AB  - Smooth muscle cell marker, SM22alpha, was down-regulated in the pathogenesis of
      arterial diseases including atherosclerosis, restenosis and abdominal aortic
      aneurysms. However, the question still exists whether this down-regulation
      actively contributes to the pathogenesis of vascular diseases. In an ongoing
      effort to understand the role of SM22alpha, here we explored transcriptome
      profiling by RNA-Seq from arteries of SM22alpha(-/-) and SM22alpha(+/+) mice.
      Analysis revealed that the most enriched pathways caused by SM22alpha-knockout
      were hematopoiesis, inflammation and lipid metabolism, respectively, and NF
      kappaB, RXRalpha and PPARalpha were the major upstream regulators. The candidate
      genes involved in inflammation and lipid metabolism were clustered in
      atherosclerosis. Thus we suspected that the molecular basis in SM22alpha(-/-)
      mice was already prepared for the initiation of atherosclerosis. Further analysis
      suggested the up-regulated TNF caused NF-kappaB pathway activation. Our results
      showed loss of SM22alpha exacerbated TNF-alpha-mediated NF-kappaB activation and
      increased the expression levels of ApoCI in vitro, while overexpression of
      SM22alpha suppressed TNF-alpha-mediated NF-kappaB activation. In addition,
      disruption of SM22alpha enhanced injury-induced neointimal hyperplasia, and
      increased expression levels of molecules related with cellular adhesion and
      extracellular matrix degradation. Taken together, these findings not only
      suggested down-regulation of SM22alpha can actively contribute to the
      pathogenesis of atherosclerosis from the molecular basis, but also further
      confirmed that the vascular cells of SM22alpha(-/-) mice may become more
      sensitive to extracellular stimulation, increasing its tendency to develop
      vascular diseases. Meanwhile, rescuing SM22alpha expression may provide a novel
      therapeutic strategy for arterial diseases. 

PMID- 24735830
TI  - Tri-iodo-l-thyronine promotes the maturation of human cardiomyocytes-derived from
      induced pluripotent stem cells.
AB  - BACKGROUND: Cardiomyocytes derived from human induced pluripotent stem cells
      (hiPSC-CMs) have great potential as a cell source for therapeutic applications
      such as regenerative medicine, disease modeling, drug screening, and toxicity
      testing. This potential is limited, however, by the immature state of the
      cardiomyocytes acquired using current protocols. Tri-iodo-l-thyronine (T3) is a
      growth hormone that is essential for optimal heart growth. In this study, we
      investigated the effect of T3 on hiPSC-CM maturation. METHODS AND RESULTS: A one
      week treatment with T3 increased cardiomyocyte size, anisotropy, and sarcomere
      length. T3 treatment was associated with reduced cell cycle activity, manifest as
      reduced DNA synthesis and increased expression of the cyclin-dependent kinase
      inhibitor p21. Contractile force analyses were performed on individual
      cardiomyocytes using arrays of microposts, revealing an almost two-fold higher
      force per-beat after T3 treatment and also an enhancement in contractile
      kinetics. This improvement in force generation was accompanied by an increase in
      rates of calcium release and reuptake, along with a significant increase in
      sarcoendoplasmic reticulum ATPase expression. Finally, although mitochondrial
      genomes were not numerically increased, extracellular flux analysis showed a
      significant increase in maximal mitochondrial respiratory capacity and
      respiratory reserve capability after T3 treatment. CONCLUSIONS: Using a broad
      spectrum of morphological, molecular, and functional parameters, we conclude that
      T3 is a driver for hiPSC-CM maturation. T3 treatment may enhance the utility of
      hiPSC-CMs for therapy, disease modeling, or drug/toxicity screens.

PMID- 24735831
TI  - No evidence of a longitudinal association between diurnal cortisol patterns and
      cognition.
AB  - We examined the effect of salivary cortisol on cognitive performance and decline
      in 3229 adults (79% men), mean age 61 years. Six saliva samples over the day
      along with a cognition test battery were administered twice in 5 years. In fully
      adjusted cross-sectional analyses from 2002 to 2004, higher waking cortisol was
      associated with higher reasoning score (beta = 0.08, 95% confidence interval:
      0.01, 0.15) but this finding was not replicated using data from 2007 to 2009.
      Over the mean 5 years follow-up there was decline in all cognitive tests but this
      decline did not vary as a function of cortisol levels; the exception was among
      APOE e4 carriers where a flatter diurnal slope and higher bedtime cortisol were
      associated with faster decline in verbal fluency. Changes in cortisol measures
      between 2002/2004 and 2007/2009 or chronically elevated levels were not
      associated with cognitive performance in 2007/2009. These results, based on a
      large sample of community-dwelling adults suggest that variability in
      hypothalamic-pituitary-adrenal function is not a strong contributor to cognitive
      aging.

PMID- 24735833
TI  - Elevation discrepancies between MMPI-2 clinical and MMPI-2-RF restructured
      clinical (RC) scales in people with seizure disorders.
AB  - PURPOSE: People with seizure disorders experience elevated rates of
      psychopathology, often undiagnosed and untreated. Accurate diagnosis of
      psychopathology remains an important goal of quality health care for people with
      seizure disorders. One of the most widely used dimensional measures of
      psychopathology is the Minnesota Multiphasic Personality Inventory-Second Edition
      (MMPI-2). Research in heterogeneous mental health samples suggests that the 2008
      revision of this measure, the Minnesota Multiphasic Personality Inventory-Second
      Edition-Restructured Form (MMPI-2-RF), offers better construct fidelity and more
      cost-effective administration. This study seeks to extend research on MMPI-2-RF
      scale elevations to a sample of people with seizure disorders. METHODS: In a
      consecutive, heterogeneous sample of people with seizure disorders, MMPI-2 and
      MMPI-2-RF scores were compared in terms of categorical classification agreement
      (clinically elevated versus not clinically elevated). Scores were also compared
      in terms of variance attributable to diagnosis-specific items, general
      demoralization, subtle items, social desirability, and demographic factors. KEY
      FINDINGS: Scores on MMPI-2 and MMPI-2-RF provided a statistically significant
      level of agreement between corresponding clinical diagnostic scales ranging from
      68% to 84%. Most classification disagreement was attributable to MMPI-2 clinical
      scale elevations when MMPI-2-RF scales were not elevated. Regression analysis
      supported the interpretation that general demoralization, subtle items, social
      desirability, and demographic factors led to MMPI-2 clinical scale elevations.
      SIGNIFICANCE: The results provide evidence that in the context of strong
      psychopathology classification agreement, the MMPI-2-RF restructured clinical
      scales provide better construct fidelity compared with the more trait
      heterogeneous MMPI-2 clinical scales. These results should encourage clinicians
      to use the MMPI-2 Restructured Form (MMPI-2-RF) for improved psychopathology
      assessment compared with the MMPI-2 in patients with seizure disorders.

PMID- 24735834
TI  - Nitric oxide mediates the anticonvulsant effects of thalidomide on
      pentylenetetrazole-induced clonic seizures in mice.
AB  - Thalidomide is an old glutamic acid derivative which was initially used as a
      sedative medication but withdrawn from the market due to the high incidence of
      teratogenicity. Recently, it has reemerged because of its potential for
      counteracting number of diseases, including neurodegenerative disorders. Other
      than the antiemetic and hypnotic aspects, thalidomide exerts some anticonvulsant
      properties in experimental settings. However, the underlying mechanisms of
      thalidomide actions are not fully realized yet. Some investigations revealed that
      thalidomide could elicit immunomodulatory or neuromodulatory properties by
      affecting different targets, including cytokines (such as TNF alpha),
      neurotransmitters, and nitric oxide (NO). In this regard, we used a model of
      clonic seizure induced by pentylenetetrazole (PTZ) in male NMRI mice to
      investigate whether the anticonvulsant effect of thalidomide is affected through
      modulation of the l-arginine-nitric oxide pathway or not. Injection of a single
      effective dose of thalidomide (10 mg/kg, i.p. or higher) significantly increased
      the seizure threshold (P<0.05). On the one hand, pretreatment with low and per se
      noneffective dose of l-arginine [NO precursor] (10, 30 and 60 mg/kg) prevented
      the anticonvulsant effect of thalidomide. On the other hand, NOS inhibitors [l
      NAME and 7-NI] augmented the anticonvulsant effect of a subeffective dose of
      thalidomide (1 and 5 mg/kg, i.p.) at relatively low doses. Meanwhile, several
      doses of aminoguanidine [an inducible NOS inhibitor] (20, 50 and 100 mg/kg)
      failed to alter the anticonvulsant effect of thalidomide significantly. In
      summary, our findings demonstrated that the l-arginine-nitric oxide pathway can
      be involved in the anticonvulsant properties of thalidomide, and the role of
      constitutive nNOS is prominent in the reported neuroprotective feature.

PMID- 24735835
TI  - Use of antiepileptic drugs and lipid-lowering agents in the United States.
AB  - INTRODUCTION: The extent to which enzyme-inducing antiepileptic drugs (EIAEDs)
      are used as first-line treatment in the United States remains unknown. Studies
      suggest that EIAEDs produce elevation of serum lipids, which could require
      additional treatment. We assessed the current use of EIAED in monotherapy for
      epilepsy in the U.S., as well as the correlation between the use of EIAEDs and
      subsequent new prescriptions for HMG-CoA reductase inhibitors ("statins") for
      hyperlipidemia. METHODS: We queried the MarketScan databases between July 2009
      and January 2013, covering 66 million patients with commercial or supplemental
      Medicare insurance. We identified individuals who had a diagnosis of seizures,
      continuous enrollment in the database from 6months prior to 24 months after the
      epilepsy diagnosis, no utilization of an AED or a statin prior to that diagnosis,
      and at least 1 new AED prescription. We tabulated the fraction of subjects who
      were prescribed EIAEDs (phenytoin, carbamazepine, or barbiturates) and those
      prescribed all other AEDs. Rates of new statin prescription between 1 and
      24months after AED prescription were assessed among the two groups, restricted to
      those with no prior history of vascular disease who had lipid serology obtained
      subsequent to the new AED prescription. RESULTS: Of the 11,893 patients with
      newly treated epilepsy, 2425 (20.4%) were started on an EIAED, and 9468 (79.6%)
      were started on a noninducing AED. There was a consistent and significant trend
      for EIAEDs to be increasingly prescribed with increasing age (p<0.0001). Among
      patients meeting the criteria, 66 (13.3%) of 496 EIAED-treated patients and 178
      (9.2%) of 1930 noninducing AED patients were newly prescribed a statin (p<0.007).
      This difference remained significant after accounting for age and gender
      (p=0.015). A patient who was started on an EIAED was 46% more likely to be
      subsequently prescribed a statin than a patient who was started on a noninducing
      AED (95% CI=1.08-1.98). CONCLUSIONS: Enzyme-inducing antiepileptic drug
      prescription for epilepsy appears to increase with increasing age in the U.S.
      despite the absence of a cogent rationale for this practice, suggesting a failure
      to appreciate the complications of EIAED therapy among U.S. physicians. Statins
      were more often prescribed to those newly treated with EIAEDs compared with those
      given noninducing AEDs. These preliminary data provide further evidence
      suggesting that EIAEDs elevate lipids in a clinically meaningful manner.

PMID- 24735837
TI  - Shift focus from treatment to encouraging health, safety guru tells conference.

PMID- 24735836
TI  - Radiometrical, hormonal and biological correlates of skeletal growth in the
      female rat from birth to senescence.
AB  - OBJECTIVE: We investigated the skeletal growth profile of female rats from birth
      to senescence (100weeks) on the basis of sequential radiometrical, hormonal and
      biochemical parameters. DESIGN: Weaning rats entered the study which was divided
      into two sections: a) sequential measurements of vertebral and tibial growths and
      bone mineral density (BMD), estimation of mineral content of the entire skeleton
      (BMC) and chemical analysis of vertebral Ca; and b) determination of basal and
      pulsatile growth hormone (rGH), insulin-like growth hormone (IGF-I), estradiol
      (E2), parathyroid hormone (PTH), osteocalcin (OC) and urinary d-pyridinoline (dp)
      throughout the experimental period. RESULTS: Vertebral and tibial growths ceased
      at week 25 whereas BMD and BMC as well as total vertebral Ca exhibited a peak
      bone mass at week 40. rGH pulsatile profiles were significantly higher in younger
      animals coinciding with the period of active growth and IGF-I peaked at 7weeks,
      slowly declining thereafter and stabilizing after week 60. OC and dp closely
      paralleled IGF-I coinciding with the period of enhanced skeletal growth,
      remaining thereafter in the low range indicative of reduced bone turnover. E2
      increased during reproductive life but the lower values subsequently recorded
      were still in the physiological range, strongly suggesting a protective role of
      this steroid on bone remodeling. PTH followed a similar profile to E2, but the
      significance of this after completion of growth remains unclear. CONCLUSIONS:
      Mechanisms governing skeletal growth in the female rat appear similar to those in
      humans. Bone progression and attainment of peak bone mass are under simultaneous
      control of rGH, IGF-I and calciotropic hormones and are modulated by E2. This
      steroid seems to protect the skeleton from resorption before senescence whereas
      the role of PTH in this context remains uncertain.

PMID- 24735832
TI  - Fungal allergy in asthma-state of the art and research needs.
AB  - Sensitization to fungi and long term or uncontrolled fungal infection are
      associated with poor control of asthma, the likelihood of more severe disease and
      complications such as bronchiectasis and chronic pulmonary aspergillosis.
      Modelling suggests that >6.5 million people have severe asthma with fungal
      sensitizations (SAFS), up to 50% of adult asthmatics attending secondary care
      have fungal sensitization, and an estimated 4.8 million adults have allergic
      bronchopulmonary aspergillosis (ABPA). There is much uncertainty about which
      fungi and fungal allergens are relevant to asthma, the natural history of
      sensitisation to fungi, if there is an exposure response relationship for fungal
      allergy, and the pathogenesis and frequency of exacerbations and complications.
      Genetic associations have been described but only weakly linked to phenotypes.
      The evidence base for most management strategies in ABPA, SAFS and related
      conditions is weak. Yet straightforward clinical practice guidelines for
      management are required. The role of environmental monitoring and optimal means
      of controlling disease to prevent disability and complications are not yet clear.
      In this paper we set out the key evidence supporting the role of fungal exposure,
      sensitisation and infection in asthmatics, what is understood about pathogenesis
      and natural history and identify the numerous areas for research studies. 

PMID- 24735838
TI  - Compression of the superior caval vein by an aneurysmal right pulmonary artery in
      a patient with absent pulmonary valve syndrome.
AB  - We report a unique case of compression of the superior caval vein by an
      aneurysmal right pulmonary artery in a patient with tetralogy of Fallot with
      absent pulmonary valve. 

PMID- 24735839
TI  - Medical complications and deaths in 21 and 56 km road race runners: a 4-year
      prospective study in 65 865 runners--SAFER study I.
AB  - BACKGROUND: Cardiac arrest and sudden death during distance-running events have
      been reported but other medical complications, including serious life-threatening
      complications have not been well described. OBJECTIVE: To document the incidence
      and nature of medical complications during 21 and 56 km running races. DESIGN:
      Prospective study. SETTING: Two Oceans Marathon races (21 and 56 km races).
      PARTICIPANTS: 65 865 race starters (39 511-21 km runners, 26 354-56 km runners).
      METHODS: Medical complications (defined as any runner requiring assessment by a
      doctor at the race medical facility or a local hospital on race day) were
      recorded in each of the 4 years of the study period. Complications were further
      subdivided into serious (potentially life-threatening) complications and deaths
      and were also analysed by system and final diagnosis. RESULTS: In the 4 years,
      545 medical complications were recorded, resulting in an overall incidence (per
      1000 race starters) of 8.27. The incidence of serious (potentially life
      threatening) medical complications was 0.56 (37 serious complications). Two
      deaths occurred in 21 km runners (incidence of 0.05). The most common specific
      medical complications were exercise-associated collapse (postural hypotension),
      dermatological conditions, musculoskeletal injuries and serious exercise
      associated muscle cramping. CONCLUSIONS: The incidence of medical complications
      was higher in 56 km runners but sudden cardiac deaths only occurred in 21 km
      runners. Serious medical complications were as common in 21 km as in 56 km
      runners. Risk factors for medical complications need to be determined in 21 and
      56 km runners to plan strategies to reduce the risk of adverse medical events in
      endurance runners.

PMID- 24735840
TI  - Australian football players' Achilles tendons respond to game loads within 2
      days: an ultrasound tissue characterisation (UTC) study.
AB  - BACKGROUND/AIM: The Achilles tendon is a tissue that responds to mechanical loads
      at a molecular and cellular level. In vitro and in vivo studies have shown that
      the expression of anabolic and/or catabolic proteins can change within hours of
      loading and return to baseline levels within 72 h. These biochemical changes have
      not been correlated with changes in whole tendon structure on imaging. We
      examined the nature and temporal sequence of changes in Achilles tendon structure
      in response to competitive game loads in elite Australian football players.
      METHODS: Elite male Australian football players with no history of Achilles
      tendinopathy were recruited. Achilles tendon structure was quantified using
      ultrasound tissue characterisation (UTC) imaging, a valid and reliable measure of
      intratendinous structure, the day prior to the match (day 0), and then reimaged
      on days 1, 2 and 4 postgame. RESULTS: Of the 18 participants eligible for this
      study, 12 had no history of tendinopathy (NORM) and 6 had a history of patellar
      or hamstring tendinopathy (TEN). Differences in baseline UTC echopattern were
      observed between the NORM and TEN groups, with the Achilles of the TEN group
      exhibiting altered UTC echopattern, consistent with a slightly disorganised
      tendon structure. In the NORM group, a significant reduction in echo-type I
      (normal tendon structure) was seen on day 2 (p=0.012) that returned to baseline
      on day 4. SUMMARY: There was a transient change in UTC echopattern in the
      Achilles tendon as a result of an Australian football game in individuals without
      a history of lower limb tendinopathy.

PMID- 24735841
TI  - Pilot and feasibility studies: is there a difference from each other and from a
      randomised controlled trial?
AB  - BACKGROUND: A crucial part in the development of any intervention is the
      preliminary work carried out prior to a large-scale definitive trial. However,
      the definitions of these terms are not clear cut and many authors redefine them.
      Because of this, the terms feasibility and pilot are often misused. AIM: To
      provide an introduction to the topic area of pilot and feasibility trials and
      draw together the work of others in the area on defining what is a pilot or
      feasibility study. METHODS: This study used a review of definitions and advice
      from the published literature and from funders' websites. Examples are used to
      show evidence of good practice and poor practice. RESULTS: We found that
      researchers use different terms to describe the various stages of the research
      process. Some define the terms feasibility and pilot as being different whereas
      others argue that these terms are synonymous. All reflective papers agree that
      feasibility/pilot studies should not test treatment comparisons nor estimate
      feasible effect sizes. However, this is not universally observed in practice.
      SUMMARY: We believe that the term 'feasibility' should be used as an overarching
      term for preliminary studies and the term 'pilot' refers to a specific type of
      study which resembles the intended trial in aspects such as, having a control
      group and randomisation. However, studies labelled 'pilot' should have different
      aims and objectives to main trials and also should include an intention for
      future work. Researchers should not use the title 'pilot' for a trial which
      evaluates a treatment effect.

PMID- 24735842
TI  - The anatomical substrate of cerebellar mutism.
AB  - Up to 39% of children operated for a posterior fossa tumor develop the cerebellar
      mutism syndrome. Although they are alert and cooperative, with normal language
      comprehension, they are unable to speak. In addition, patients may demonstrate
      apathy, bladder and bowel incontinence and long-term language and cognitive
      disturbances. This devastating syndrome is at the same time intriguing, because
      it confirms a role for the cerebellum in language and cognitive functions. Recent
      investigations have led to new insights regarding the cerebellar mutism syndrome.
      The commonly accepted hypothesis states that the mutism is caused by a
      hypofunction of cerebral hemispheres, due to damage to the superior cerebellar
      peduncle and functional disruption of the cerebello-cerebral circuitry. This
      article focuses on the evidence for and against this hypothesis and its clinical
      consequences. 

PMID- 24735843
TI  - Fulminant diffuse systemic sclerosis following aortic valve replacement.
AB  - We present a case of fulminant diffuse systemic sclerosis (dSSc) developed after
      the aortic valve replacement followed by fatal congestive heart failure within
      the 6 months from the initial symptoms. A 61-year-old male developed rapidly
      progressive diffuse systemic sclerosis following aortic valve replacement due to
      stenosis of bicuspid aortic valve. He presented with diarrhoea, weight loss,
      mialgia and arthralgia after cardiac surgery. Heart failure, due to myocardial
      fibrosis, was noted as a cause of death. We hypothesize that artificial materials
      like the ones used in mechanical valves or silicon materials in breast implants
      may induce fulminant course of pre-existing systemic sclerosis or create a new
      onset in predisposed individual.

PMID- 24735844
TI  - Perforin- and granulysin-mediated cytotoxicity and interleukin 15 play roles in
      neurocognitive impairment in patients with acute lymphoblastic leukaemia.
AB  - Acute lymphoblastic leukaemia (ALL) is an aggressive disease. The course of
      disease is regulated by pro-inflammatory agents, and malignant cell infiltration
      of tissues plays a deleterious role in disease progression, greatly impacting
      quality of life, especially in the cognitive domains. Our hypothesis is that
      significant serum concentrations of interleukin 15 (IL-15) are responsible for
      higher expression of adhesion molecules on endothelial cells of blood-brain
      barrier (BBB) which allow leukaemia cells and/or normal lymphocytes the
      infiltration into the brain. In brain tissue these cells could be stimulated to
      release perforin and granulysin causing induction of apoptosis in brain cells
      that are involved in complex neural signalling mediated by neurotransmitters, and
      consequent fine cognitive impairment. Such changes could be detected early, even
      before notable clinical psycho-neurological or radiological changes in patients
      with ALL. To evaluate this hypothesis we propose measuring cognitive function
      using Complex Reactiometer Drenovac (CRD) scores in patients with ALL. The
      expression of different adhesion molecules on BBB as well as presence and
      distribution of different lymphocytes in brain tissue will be analyzed. We will
      then correlate CRD scores with levels of IL-15 and the percentages of T cells,
      natural killer T cells, and natural killer cells expressing perforin and/or
      granulysin proteins. CRD is a scientifically recognised and highly sensitive
      psychometric laboratory test based on the complex chronometric mathematical
      measuring of speed of reaction to various stimuli. It provides an objective
      assessment of cognitive functions from the most complex mental activities to the
      simplest reaction reflexes. Early recognition of cognitive dysfunction might be
      important when selecting the most appropriate chemotherapy and/or radiotherapy
      regimens, and could allow for the implementation of preventive measures against
      further deterioration in cognitive function and quality of life in patients with
      ALL.

PMID- 24735845
TI  - Transplantation of adipose-derived stem cells combined with decellularized
      cartilage ECM: a novel approach to nasal septum perforation repair.
AB  - Nasal septal perforation, a defect of the nasal mucoperichondrium and cartilage,
      may induce epistaxis, persistent rhinorrhea and nasal obstruction. Cell-based
      tissue engineering is a promising therapeutic method for the treatment of nasal
      septal perforation. However, lack of an adequate source of cells and unsuitable
      biomaterials greatly hinder the development of cell-based therapy. In this paper,
      we proposed the application of adipose-derived stem cells combined with
      decellularized cartilage ECM as a potential graft for the damaged nasal septum,
      which could help to repair the mucosal and cartilage tissues in the treatment of
      nasal septal perforation. This new technology could play a novel role in the
      repair of nasal septal perforation, and in regeneration of damaged nasal
      cartilage. 

PMID- 24735846
TI  - Physiological organization of immune response based on the homeostatic mechanism
      of matrix reprogramming: implication in tumor and biotechnology.
AB  - It is accepted that the immune system responds to pathogens with activation of
      antigen-independent innate and antigen-dependent adaptive immunity. However many
      immune events do not fit or are even inconsistent with this notion. We developed
      a new homeostatic model of the immune response. This model consists of four
      units: a sensor, a regulator, an effector and a rehabilitator. The sensor,
      macrophages or lymphocytes, recognize pathogenic cells and generate alarm
      signals. The regulator, antigen-presenting cells, Tregs and myeloid-derived
      suppressor cells, evaluate the signals and together with sensor cells program the
      effector. The effector, programmed macrophages and lymphocytes, eliminate the
      pathogenic cells. The rehabilitator, M2 macrophages, restrict inflammation,
      provide angiogenesis and reparation of tissue damage, and restore the
      homeostasis. We suggest the terms "immune matrix" for a biological template of
      immune responses to pathogens and "matrix reprogramming" for the interdependent
      reprogramming of different cells in the matrix. In an adequate immune response,
      the matrix forms a negative feedback mechanism to support the homeostasis. We
      defined the cellular and phenotypic composition of a tumor immune matrix. A tumor
      reprograms the homeostatic negative feedback mechanism of matrix into a
      pathogenic positive feedback mechanism. M2 macrophages play a key role in this
      transformation. Therefore, macrophages are an attractive target for
      biotechnology. Based on our hypotheses, we are developing a cell biotechnology
      method for creation of macrophages with a stable antitumor phenotype. We have
      shown that such macrophages almost doubled the survival time of mice with tumor. 

PMID- 24735847
TI  - Hype in Halifax.

PMID- 24735848
TI  - Sex.

PMID- 24735849
TI  - Spectraplakins.

PMID- 24735850
TI  - Temporal prediction errors in visual and auditory cortices.
AB  - To form a coherent percept of the environment, the brain needs to bind sensory
      signals emanating from a common source, but to segregate those from different
      sources [1]. Temporal correlations and synchrony act as prominent cues for
      multisensory integration [2-4], but the neural mechanisms by which such cues are
      identified remain unclear. Predictive coding suggests that the brain iteratively
      optimizes an internal model of its environment by minimizing the errors between
      its predictions and the sensory inputs [5,6]. This model enables the brain to
      predict the temporal evolution of natural audiovisual inputs and their
      statistical (for example, temporal) relationship. A prediction of this theory is
      that asynchronous audiovisual signals violating the model's predictions induce an
      error signal that depends on the directionality of the audiovisual asynchrony. As
      the visual system generates the dominant temporal predictions for visual leading
      asynchrony, the delayed auditory inputs are expected to generate a prediction
      error signal in the auditory system (and vice versa for auditory leading
      asynchrony). Using functional magnetic resonance imaging (fMRI), we measured
      participants' brain responses to synchronous, visual leading and auditory leading
      movies of speech, sinewave speech or music. In line with predictive coding,
      auditory leading asynchrony elicited a prediction error in visual cortices and
      visual leading asynchrony in auditory cortices. Our results reveal predictive
      coding as a generic mechanism to temporally bind signals from multiple senses
      into a coherent percept. 

PMID- 24735851
TI  - Evolution: don't be so butch, dear!
AB  - Simultaneous hermaphrodites are both male and female, which could lead to
      conflicts between partners over optimal investment to the two sex functions. New
      evidence from hermaphroditic freshwater snails suggests that transferred seminal
      fluids affect the partner's male function.

PMID- 24735852
TI  - Neural energetics: hungry flies turn down the visual gain.
AB  - Food-deprived flies reduce the gain of a visual-motion-sensitive interneuron
      whilst walking, and the optomotor reflex to which it contributes, providing
      evidence of coupling between nutritional state, behavior and neural activity.

PMID- 24735853
TI  - Microbial ecology: finding structure in the rare biosphere.
AB  - Protists (unicellular eukaryotes) play important roles in marine ecosystems but
      are tremendously diverse and many remain uncharacterized. Deep-sequencing of a
      universal marker gene has helped resolve community composition patterns among
      rare and abundant protistan sequence groups in coastal European waters.

PMID- 24735854
TI  - Protein translocation: the Sec61/SecYEG translocon caught in the act.
AB  - The Sec61/SecYEG complex mediates both the translocation of newly synthesized
      proteins across the membrane and the integration of transmembrane segments into
      the lipid bilayer. New cryo-electron microscopy studies show ribosome-channel
      complexes in action and reveal their repertoire of conformational states.

PMID- 24735855
TI  - Animal communication: keep your wings off my food!
AB  - When foraging, male big brown bats produce ultrasonic social calls. The calls
      repel rival bats from the caller and its prey, and increase the caller's foraging
      success during their high-speed aerial excursions.

PMID- 24735856
TI  - Neuroeconomics: a formal test of dopamine's role in reinforcement learning.
AB  - Over the last two decades, dopamine and reinforcement learning have been
      increasingly linked. Using a novel, axiomatic approach, a recent study shows that
      dopamine meets the necessary and sufficient conditions required by the theory to
      encode a reward prediction error.

PMID- 24735857
TI  - Cytoskeleton: septins do the horizontal tango.
AB  - Septins are a family of membrane-associated filamentous proteins that are
      essential in many biological processes, such as cell division. A recent study has
      provided the first visualization of septin filament formation in real time,
      leading to important new insights into their organization.

PMID- 24735858
TI  - Neural circuits: anatomy of a sexual behavior.
AB  - Females of many species, once mated, undergo a rapid change in reproductive
      physiology and behavior, shifting from a sexually receptive state to one devoted
      to the rearing of offspring. Two recent reports shed light on the neural
      circuitry governing the female post-mating response in the fruit fly Drosophila,
      providing insight into the neurobiological processes governing a complex
      behavior.

PMID- 24735860
TI  - Understanding low uptake of mass treatment for intestinal schistosomiasis among
      school children: a qualitative study in Jinja district, Uganda.
AB  - Despite attempts to control intestinal schistosomiasis through school-based mass
      drug administration (MDA) with praziquantel using school teachers in Uganda, less
      than 30% of the school children take the treatment in some areas. The aim of the
      study was to understand why the uptake of praziquantel among school children is
      low and to suggest strategies for improved uptake. This was a cross-sectional
      qualitative study in which 24 focus group discussions and 15 key informant
      interviews were conducted 2 months after MDA. The focus group discussions were
      held with school children in twelve primary schools and the key informant
      interviews were held with school teachers, sub-county health assistants and the
      District Vector Control Officer. The study shows that the low uptake of
      praziquantel among school children is a result of a complex interplay between
      individual, interpersonal, institutional, community and public policy factors.
      The individual and interpersonal factors underpinning the low uptake include
      inadequate information about schistosomiasis prevention, beliefs and attitudes in
      the community about treatment of schistosomiasis and shared concerns among
      children and teachers about the side-effects of praziquantel, especially when the
      drug is taken on an empty stomach. The institutional, policy and community
      factors include inadequate preparation and facilitation of teachers and the
      school feeding policy, which requires parents to take responsibility for
      providing their children with food while at school, yet many parents cannot meet
      the cost of a daily meal due to the prevailing poverty in the area. It is
      concluded that strategies to improve uptake of praziquantel among school children
      need to be multi-pronged addressing not only the preparation and motivation of
      teachers and health education for children, but also the economic and political
      aspects of drug distribution, including the school feeding policy. 

PMID- 24735859
TI  - Neural mechanisms of self-location.
AB  - The ability to self-localise and to navigate to remembered goals in complex and
      changeable environments is crucial to the survival of many mobile species.
      Electrophysiological investigations of the mammalian hippocampus and associated
      brain structures have identified several classes of neurons which represent
      information about an organism's position and orientation. These include place
      cells, grid cells, head direction cells, and boundary vector cells, as well as
      cells representing aspects of self-motion. Understanding how these neural
      representations are formed and updated from environmental sensory information and
      from information relating to self-motion is an important topic attracting
      considerable current interest. Here we review the computational mechanisms
      thought to underlie the formation of these different spatial representations, the
      interactions between them, and their use in guiding behaviour. These include some
      of the clearest examples of computational mechanisms of general interest to
      neuroscience, such as attractor dynamics, temporal coding and multi-modal
      integration. We also discuss the close relationships between computational
      modelling and experimental research which are driving progress in this area.

PMID- 24735861
TI  - ATF-2/CREB/IRF-3-targeted anti-inflammatory activity of Korean red ginseng water
      extract.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Korean Red Ginseng (KRG) is one of the
      representative traditional herbal medicines prepared from Panax ginseng Meyer
      (Araliaceae) in Korea. It has been reported that KRG exhibits a lot of different
      biological actions such as anti-aging, anti-fatigue, anti-stress, anti
      atherosclerosis, anti-diabetic, anti-cancer, and anti-inflammatory activities.
      Although systematic studies have investigated how KRG is able to ameliorate
      various inflammatory diseases, its molecular inhibitory mechanisms had not been
      carried out prior to this study. MATERIALS AND METHODS: In order to investigate
      these mechanisms, we evaluated the effects of a water extract of Korean Red
      Ginseng (KRG-WE) on the in vitro inflammatory responses of activated RAW264.7
      cells, and on in vivo gastritis and peritonitis models by analyzing the
      activation events of inflammation-inducing transcription factors and their
      upstream kinases. RESULTS: KRG-WE reduced the production of nitric oxide (NO),
      protected cells against NO-induced apoptosis, suppressed mRNA levels of inducible
      NO synthase (iNOS), cyclooxygenase (COX)-2, and interferon (IFN)-beta,
      ameliorated EtOH/HCl-induced gastritis, and downregulated peritoneal exudate
      derived NO production from lipopolysaccharide (LPS)-injected mice. The inhibition
      of these inflammatory responses by KRG-WE was regulated through the suppression
      of p38, c-Jun N-terminal kinase (JNK), and TANK-binding kinase 1 (TBK1) and by
      subsequent inhibition of activating transcription factor (ATF)-2, cAMP response
      element-binding protein (CREB), and IRF-3 activation. Of ginsensides included in
      this extract, interestingly, G-Rc showed the highest inhibitory potency on IRF-3
      mediated luciferase activity. CONCLUSION: These results strongly suggest that the
      anti-inflammatory activities of KRG-WE could be due to its inhibition of the
      p38/JNK/TBK1 activation pathway.

PMID- 24735862
TI  - Sub-acute toxicity of the chloroformic extract of Rapanea melanophloeos (L.) Mez
      in rats.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Cape beech (Rapanea melanophloeos) is an
      important medicinal plant that is widely used in most of Africa. Currently,
      little toxicological information is available on its safety following prolonged
      use. AIM OF THE STUDY: In this study, we sought to evaluate the oral sub-acute
      toxicity of Rapanea melanophloeos stem bark chloroformic extract using Sprague
      Dawley rats. MATERIALS AND METHODS: Six-week old rats were orally administered
      with the extract at dosage levels of 100 mg/kg, 300 mg/kg and 1000 mg/kg for 28
      days. Clinical signs, hematological and clinical chemistry parameters were
      monitored, while organ weights and organ pathology were evaluated at the end of
      the study. RESULTS: The extract caused a significant reduction in bodyweight at
      1000 mg/kg. The hematological profiles of animals at this dose showed an increase
      in the erythrocyte count and the hematocrit that were accompanied by decrease in
      the mean corpuscular hemoglobin and mean corpuscular hemoglobin concentration.
      Biochemical parameters were not altered in a dose-related manner when compared to
      the controls. There were time associated alterations on both hematological and
      biochemical parameters, but pathological examination did not reveal any treatment
      related changes in any of the organs. CONCLUSION: Our results demonstrate that
      the chloroformic stem bark extract of Rapanea melanophloeos may be of no
      toxicological concern at dosage levels up to 1000mg/kg. Rapanea melanophloeos can
      therefore be used confidently in African traditional medicine at these or lower
      dosage levels.

PMID- 24735863
TI  - Hugan Qingzhi medication ameliorates hepatic steatosis by activating AMPK and
      PPARalpha pathways in L02 cells and HepG2 cells.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Hugan Qingzhi tablet (HQT), a lipid- lowering
      traditional Chinese medicine formula, has been used for the prevention and
      treatment of nonalcoholic fatty liver (NAFLD). AIM OF THE STUDY: This study was
      realized to evaluate the effects of HQT-medicated serum on hepatic steatosis
      using in vitro experiments with cells and explore the relevant mechanisms with
      method of serum pharmacology. MATERIALS AND METHODS: A model of hepatic steatosis
      in the L02 and HepG2 cells was induced by free fatty acid (FFA). The components
      in the HQT-medicated serum were assayed by high-performance liquid
      chromatography. Intracellular lipid droplets were detected by Oil Red O staining,
      and their ultrastructure was examined by transmission electron microscope. The
      biochemical parameters, including triglyceride (TG), lactate dehydrogenase (LDH),
      aspartate aminotransferase (AST) and alanine aminotransferase (ALT), total
      antioxidant capacity (T-AOC), malondialdehyde (MDA), superoxide dismutase (SOD)
      and glutathione (GSH), were measured with commercial kits. Furthermore, the
      expression of adiponectin, AMP-activated protein kinase (AMPK) phosphorylation,
      sterol regulatory element-binding protein 1 (SREBP-1), peroxisome proliferator
      activated receptor-alpha (PPARalpha), carnitine palmitoyltransferase 1 (CPT-1),
      and acetyl-CoA oxidase 1 (ACOX1) was analyzed by Western blot and/or quantitative
      reverse transcription-polymerase chain reaction (qRT-PCR). RESULTS: Moderate- and
      high-dose HQT-medicated serum reduced (P<0.05 or P<0.01) the accumulation of
      lipid droplets and the cellular TG content in L02 and HepG2 cells. They caused
      significant reductions (P<0.01) in LDH, AST, ALT and MDA and significant increase
      (P<0.05 or P<0.01) in T-AOC in the culture medium. They also caused increase
      (P<0.05 or P<0.01) in GSH level and SOD activity in FFA-induced steatotic L02 and
      HepG2 cells. Furthermore, moderate- and high-dose HQT-medicated serum enhanced
      (P<0.01) adiponectin expression in a concentration-dependent manner and increased
      (P<0.05 or P<0.01) the phosphorylation of AMPK and the expression of PPARalpha,
      CPT-1, and ACOX1, and reduced (P<0.05 or P<0.01) the expression of SREBP-1.
      CONCLUSION: The results suggested that HQT-medicated serum exerts a preventive
      effect against hepatic steatosis, and the potential mechanism might be activation
      of AMPK and PPARalpha pathways.

PMID- 24735864
TI  - An osteotomy anterolateral approach for lateral tibial plateau fractures merged
      with relatively simple and intact posterolateral corner displacement.
AB  - INTRODUCTION: This study investigates the safety and efficacy of anterolateral
      (AL) osteotomy for the treatment of lateral tibial plateau fractures merged with
      relatively simple and intact posterolateral (PL) corner displacement and screens
      applicable patients. METHODS: Totally, 11 patients with lateral tibial plateau
      fractures involving the PL corner were included in this study. Of them, seven
      patients sustained their injuries from motor vehicle accidents (MVAs), three from
      sports and one from fall from height. All of them received open reduction and
      internal fixation through the AL approach. Operation time, incision length, range
      of motion (ROM), Hospital for Special Surgery (HSS) knee score, time of union and
      complications were retrospectively reviewed. Tibial plateau angle (TPA), lateral
      posterior slope angle (PSA) and articular step-off reduction after surgery were
      examined by a radiograph technique. RESULTS: Statistically, the means of
      operation time, incision length, ROM and follow-up period were 82 min, 11 cm, 97
      degrees  and 27 months, respectively. Three patients had slight complications:
      superficial infection, hardware irritation and secondary valgus deformity,
      without severe neural or vascular injuries, which revealed the safety and
      efficacy of the PL treatment. The average HSS knee score was 91.2 (range 86-96).
      Reduction (mean TPA 87.2 degrees  and mean PSA 8.3 degrees ) was satisfactory in
      10 patients, except for one patient with a radiographic articular step-off of 5
      mm (case 10). CONCLUSIONS: The AL approach is safe and effective for lateral
      tibial plateau fractures involving the PL corner, especially for fractures merged
      with simple and intact PL corner displacement (depression and/or split).

PMID- 24735865
TI  - Beneficial pre-ECT ketamine infusion in a patient with treatment-resistant
      depression.

PMID- 24735866
TI  - Integrated models of care for medical inpatients with psychiatric disorders: a
      systematic review.
AB  - OBJECTIVE: Psychiatric disorders are common among medical inpatient settings and
      management of psychiatric disorders can be challenging in this setting.
      Integrated models of care (IMCs) combining psychiatric and medical specialties
      within a single service may improve psychiatric and medical outcomes, although
      evidence for IMCs in medical inpatient settings has not been well described.
      METHOD: We searched MEDLINE, Embase, and Google scholar for relevant articles. We
      included all randomized controlled trials or quasi-experimental studies in
      English that evaluated IMCs for medical inpatients with psychiatric disorders
      when compared with usual care. We defined IMCs as models of care where
      psychiatric and medical providers had joint responsibility for all patients
      within a given service. We extracted information on the characteristics of IMCs
      and on the effects of IMCs on psychiatric, medical, and health service outcomes.
      RESULTS: Four studies met the inclusion criteria, thereby including 716
      participants overall. All studies differed in the study design, models of IMCs,
      and outcomes reported. In 2 studies, IMCs improved psychiatric symptoms compared
      with those admitted to a general medical service. Two studies demonstrated
      reductions in length of stay with IMCs compared with usual care. One study
      reported an improvement in functional outcomes and a decreased likelihood of long
      term care admission associated with IMCs when compared with usual care.
      CONCLUSIONS: There is preliminary evidence that IMCs may improve a number of
      outcomes for medical inpatients with psychiatric disorders. Additional well
      designed studies of IMCs are required to further evaluate the effect of IMCs on
      patient outcomes and costs of care.

PMID- 24735867
TI  - A survey of "mental hardiness" and "mental toughness" in professional male
      football players.
AB  - BACKGROUND: It is not uncommon for chiropractors to be associated with sports
      teams for injury prevention, treatment, or performance enhancement. There is
      increasing acceptance of the importance of sports psychology in the overall
      management of athletes. Recent findings indicate mental hardiness can be
      determined reliably using specific self-assessment questionnaires. This study set
      out to investigate the hardiness scores of professional footballers and examine
      the correlation between two questionnaires. It also included a mental hardiness
      rating of players by two coaches, and examined differences in hardiness and
      mental toughness between national and international players. METHODS: Two self
      assessment questionnaires (modified Sports Mental Toughness Questionnaire [SMTQ
      M] and Psychological Performance Inventory [PPI-A]) were completed by 20 male
      professional footballers. Two coaches, independently rated each player. A
      percentage score from each questionnaire was awarded each player and an average
      score was calculated ({SMTQ-M % + PPI-A %} / 2). The PPI-A and SMTQ-M scores
      obtained for each player were analysed for correlation with Pearson's correlation
      coefficient. Cohen's kappa inter-reliability coefficient was used to determine
      agreement between coaches, and between the players' hardiness scores and coaches'
      ratings. The independent t-test was used to examine differences between national
      and international players. RESULTS: The players' scores obtained from PPI-A and
      SMTQ-M correlated well (r = 0.709, p < 0.001). The coaches ratings showed
      significant, weak to moderate agreement (Cohen's kappa = 0.33). No significant
      agreement was found between player self-assessments and coaches' ratings. The
      average ({SMTQ-M % + PPI-A %} / 2) mean score was 77% (SD = 7.98) with
      international players scoring 7.4% (p = 0.04) higher than non-international
      players. CONCLUSIONS: The questionnaires (SMTQ-M and PPI-A) correlated well in
      their outcome scores. These findings suggest that coaches moderately agree when
      assessing the level of mental hardiness of football players. There was no
      agreement between player self-assessment and ratings by coaches. Footballers who
      play or had played for national teams achieved slightly higher mental hardiness
      scores. Either questionnaire can offer the clinician a cost-effective, valuable
      measure of an individual's psychological attributes, which could be relevant
      within the wider context of bio-psycho-social model of care.

PMID- 24735868
TI  - A genome-wide sequence-structure analysis suggests aggregation gatekeepers
      constitute an evolutionary constrained functional class.
AB  - Protein aggregation is geared by aggregation-prone regions that self-associate by
      beta-strand interactions. Charged residues and prolines are enriched at the
      flanks of aggregation-prone regions resulting in decreased aggregation. It is
      still unclear what drives the overrepresentation of these "aggregation
      gatekeepers", that is, whether their presence results from structural constraints
      determining protein stability or whether they constitute a bona fide functional
      class selectively maintained to control protein aggregation. As functional
      residues are typically conserved regardless of their cost to protein stability,
      we compared sequence conservation and thermodynamic cost of these residues in
      2659 protein families in Escherichia coli. Across protein families, we find
      gatekeepers to be under strong selective conservation while at the same time
      representing a significant thermodynamic cost to protein structure. This finding
      supports the notion that aggregation gatekeepers are not structurally determined
      but evolutionary selected to control protein aggregation. 

PMID- 24735869
TI  - The molecular basis of bacterial-insect symbiosis.
AB  - Insects provide experimentally tractable and cost-effective model systems to
      investigate the molecular basis of animal-bacterial interactions. Recent research
      is revealing the central role of the insect innate immune system, especially anti
      microbial peptides and reactive oxygen species, in regulating the abundance and
      composition of the microbiota in various insects, including Drosophila and the
      mosquitoes Aedes and Anopheles. Interactions between the immune system and
      microbiota are, however, bidirectional with evidence that members of the resident
      microbiota can promote immune function, conferring resistance to pathogens and
      parasites by both activation of immune effectors and production of toxins.
      Antagonistic and mutualistic interactions among bacteria have also been
      implicated as determinants of the microbiota composition, including exclusion of
      pathogens, but the molecular mechanisms are largely unknown. Some bacteria are
      crucial for insect nutrition, through provisioning of specific nutrients (e.g., B
      vitamins, essential amino acids) and modulation of the insect nutritional sensing
      and signaling pathways (e.g., insulin signaling) that regulate nutrient
      allocation, especially to lipid and other energy reserves. A key challenge for
      future research is to identify the molecular interaction between specific
      bacterial effectors and animal receptors, as well as to determine how these
      interactions translate into microbiota-dependent signaling, metabolism, and
      immune function in the host. 

PMID- 24735870
TI  - The nucleolar PICT-1/GLTSCR2 protein forms homo-oligomers.
AB  - The human "protein interacting with carboxyl terminus 1" (PICT-1), also
      designated as the "glioma tumor suppressor candidate region 2 gene product",
      GLTSCR2, is a nucleolar protein whose activity is, as yet, unknown. Contradictory
      results regarding the role of PICT-1 in cancer have been reported, and PICT-1 has
      been suggested to function either as a tumor suppressor protein or as an
      oncogene. In this study, we demonstrate self-association of PICT-1. Through yeast
      two-hybrid assay, we identified PICT-1 as its own interaction partner. We
      confirmed the interaction of PICT-1 with itself by direct yeast two-hybrid assay
      and also showed self-association of PICT-1 in mammalian cells by co
      immunoprecipitation and fluorescence resonance energy transfer assays.
      Furthermore, we confirmed direct self-association of PICT-1 by using in vitro
      microfluidic affinity binding assays. The later assay also identified the carboxy
      terminal domain as mediating self-interaction of PICT-1. Glutaraldehyde cross
      linking and gel-filtration assays suggest that PICT-1 forms dimers, though it may
      form higher-order complexes as well. Our findings add another layer of complexity
      in understanding the different functions of PICT-1 and may help provide insights
      regarding the activities of this protein. 

PMID- 24735872
TI  - Dextrose 10% in the treatment of out-of-hospital hypoglycemia.
AB  - INTRODUCTION: Prehospital first responders historically have treated hypoglycemia
      in the field with an IV bolus of 50 mL of 50% dextrose solution (D50). The
      California Contra Costa County Emergency Medical Services (EMS) system recently
      adopted a protocol of IV 10% dextrose solution (D10), due to frequent shortages
      and relatively high cost of D50. The feasibility, safety, and efficacy of this
      approach are reported using the experience of this EMS system. METHODS: Over the
      course of 18 weeks, paramedics treated 239 hypoglycemic patients with D10 and
      recorded patient demographics and clinical outcomes. Of these, 203 patients were
      treated with 100 mL of D10 initially upon EMS arrival, and full data on response
      to treatment was available on 164 of the 203 patients. The 164 patients'
      capillary glucose response to initial infusion of 100 mL of D10 was calculated
      and a linear regression line fit between elapsed time and difference between
      initial and repeat glucose values. Feasibility, safety, and the need for repeat
      glucose infusions were examined. RESULTS: The study cohort included 102 men and
      62 women with a median age of 68 years. The median initial field blood glucose
      was 38 mg/dL, with a subsequent blood glucose median of 98 mg/dL. The median time
      to second glucose testing was eight minutes after beginning the 100 mL D10
      infusion. Of 164 patients, 29 (18%) required an additional dose of IV D10
      solution due to persistent or recurrent hypoglycemia, and one patient required a
      third dose. There were no reported adverse events or deaths related to D10
      administration. Linear regression analysis of elapsed time and difference between
      initial and repeat glucose values showed near-zero correlation. CONCLUSIONS: In
      addition to practical reasons of cost and availability, theoretical risks of
      using 50 mL of D50 in the out-of-hospital setting include extravasation injury,
      direct toxic effects of hypertonic dextrose, and potential neurotoxic effects of
      hyperglycemia. The results of one local EMS system over an 18-week period
      demonstrate the feasibility, safety, and efficacy of using 100 mL of D10 as an
      alternative. Additionally, the linear regression line of repeat glucose
      measurements suggests that there may be little or no short-term decay in blood
      glucose values after D10 administration.

PMID- 24735871
TI  - Gly25-Ser26 amyloid beta-protein structural isomorphs produce distinct Abeta42
      conformational dynamics and assembly characteristics.
AB  - One of the earliest events in amyloid beta-protein (Abeta) self-association is
      nucleation of Abeta monomer folding through formation of a turn at Gly25-Lys28.
      We report here the effects of structural changes at the center of the turn, Gly25
      Ser26, on Abeta42 conformational dynamics and assembly. We used "click peptide"
      chemistry to quasi-synchronously create Abeta42 from 26-O-acyliso-Abeta42
      (iAbeta42) through a pH jump from 3 to 7.4. We also synthesized Nalpha-acetyl
      Ser26-iAbeta42 (Ac-iAbeta42), which cannot undergo O->N acyl chemistry, to study
      the behavior of this ester form of Abeta42 itself at neutral pH. Data from
      experiments monitoring increases in beta-sheet formation (thioflavin T, CD),
      hydrodynamic radius (RH), scattering intensity (quasielastic light scattering
      spectroscopy), and extent of oligomerization (ion mobility spectroscopy-mass
      spectrometry) were quite consistent. A rank order of Ac-iAbeta42>iAbeta42>Abeta42
      was observed. Photochemically cross-linked iAbeta42 displayed an oligomer
      distribution with a prominent dimer band that was not present with Abeta42. These
      dimers also were observed selectively in iAbeta42 in ion mobility spectrometry
      experiments. The distinct biophysical behaviors of iAbeta42 and Abeta42 appear to
      be due to the conversion of iAbeta42 into "pure" Abeta42 monomer, a nascent form
      of Abeta42 that does not comprise the variety of oligomeric and aggregated states
      present in pre-existent Abeta42. These results emphasize the importance of the
      Gly25-Ser26 dipeptide in organizing Abeta42 monomer structure and thus suggest
      that drugs altering the interactions of this dipeptide with neighboring side
      chain atoms or with the peptide backbone could be useful in therapeutic
      strategies targeting formation of Abeta oligomers and higher-order assemblies. 

PMID- 24735873
TI  - Lymnaea glabra: progressive increase in susceptibility to Fasciola hepatica
      through successive generations of experimentally infected snails.
AB  - Experimental infections of Lymnaea glabra (two populations) with Fasciola
      hepatica were carried out during seven successive snail generations, to determine
      if prevalence and intensity of snail infection increased over time through
      descendants of snails already infected with F. hepatica. Controls were
      descendants coming from uninfected parents and infected according to the same
      protocol. No larval forms were found in the bodies of control snails coming from
      uninfected parents. In contrast, prevalence and intensity of F. hepatica
      infection in snails originating from infected parents progressively increased
      from the F2 or F3 to the F6 generation of L. glabra. In another experiment
      carried out with the F7 generations of L. glabra and a single generation of Galba
      truncatula (as controls), the prevalence of F. hepatica infection and the total
      number of cercariae were lower in L. glabra (without significant differences
      between both populations). If the number of cercariae shed by infected snails was
      compared to overall cercarial production noted in snails containing cercariae but
      dying without emission, the percentage was greater in G. truncatula (69% instead
      of 52-54% in L. glabra). Even if most characteristics of F. hepatica infection
      were lower in L. glabra, prevalence and intensity of parasite infection increased
      with snail generation when tested snails came from infected parents. This mode of
      snail infection with F. hepatica suggests an explanation for cases of fasciolosis
      occurring in cattle-breeding farms where paramphistomosis is lacking and G.
      truncatula is absent. 

PMID- 24735874
TI  - Ovol proteins: guardians against EMT during epithelial differentiation.
AB  - Epithelial differentiation requires a balancing act to commit to epithelial fate
      while inhibiting both progenitor and mesenchymal traits. In this issue of
      Developmental Cell, Lee et al. (2014) and Watanabe et al. (2014) uncover a
      critical role of Ovol proteins in safeguarding this intricate process.

PMID- 24735875
TI  - Going forward with retromer.
AB  - The retromer complex is well known to mediate retrograde transport from endosomes
      to the Golgi. In a recent issue of Neuron, Choy et al. (2014) identify a function
      for retromer in supporting fast, local delivery of neurotransmitter receptors
      from endosomes to the dendritic plasma membrane.

PMID- 24735876
TI  - Friction on MAP determines its traveling direction on microtubules.
AB  - Microtubule networks generate various forces, and the forces are applied to
      microtubule-associated proteins (MAPs). Forth et al. (2014) show in a recent
      issue of Cell that asymmetric frictional force between MAPs and microtubules
      leads to directional movement of MAPs along microtubules, providing insight into
      the mechanism of microtubule network self-organization.

PMID- 24735877
TI  - Rif1 maintains telomere length homeostasis of ESCs by mediating heterochromatin
      silencing.
AB  - Telomere length homeostasis is essential for genomic stability and unlimited self
      renewal of embryonic stem cells (ESCs). We show that telomere-associated protein
      Rif1 is required to maintain telomere length homeostasis by negatively regulating
      Zscan4 expression, a critical factor for telomere elongation by recombination.
      Depletion of Rif1 results in terminal hyperrecombination, telomere length
      heterogeneity, and chromosomal fusions. Reduction of Zscan4 by shRNA
      significantly rescues telomere recombination defects of Rif1-depleted ESCs and
      associated embryonic lethality. Further, Rif1 negatively modulates Zscan4
      expression by maintaining H3K9me3 levels at subtelomeric regions.
      Mechanistically, Rif1 interacts and stabilizes H3K9 methylation complex. Thus,
      Rif1 regulates telomere length homeostasis of ESCs by mediating heterochromatic
      silencing. 

PMID- 24735878
TI  - Transcriptional mechanisms link epithelial plasticity to adhesion and
      differentiation of epidermal progenitor cells.
AB  - During epithelial tissue morphogenesis, developmental progenitor cells undergo
      dynamic adhesive and cytoskeletal remodeling to trigger proliferation and
      migration. Transcriptional mechanisms that restrict such a mild form of
      epithelial plasticity to maintain lineage-restricted differentiation in committed
      epithelial tissues are poorly understood. Here, we report that simultaneous
      ablation of transcriptional repressor-encoding Ovol1 and Ovol2 results in
      expansion and blocked terminal differentiation of embryonic epidermal progenitor
      cells. Conversely, mice overexpressing Ovol2 in their skin epithelia exhibit
      precocious differentiation accompanied by smaller progenitor cell compartments.
      We show that Ovol1/Ovol2-deficient epidermal cells fail to undertake alpha
      catenin-driven actin cytoskeletal reorganization and adhesive maturation and
      exhibit changes that resemble epithelial-to-mesenchymal transition (EMT).
      Remarkably, these alterations and defective terminal differentiation are reversed
      upon depletion of EMT-promoting transcriptional factor Zeb1. Collectively, our
      findings reveal Ovol-Zeb1-alpha-catenin sequential repression and highlight Ovol1
      and Ovol2 as gatekeepers of epithelial adhesion and differentiation by inhibiting
      progenitor-like traits and epithelial plasticity.

PMID- 24735879
TI  - Mammary morphogenesis and regeneration require the inhibition of EMT at terminal
      end buds by Ovol2 transcriptional repressor.
AB  - Epithelial cells possess remarkable plasticity, having the ability to become
      mesenchymal cells through alterations in adhesion and motility (epithelial-to
      mesenchymal transition [EMT]). However, how epithelial plasticity is kept in
      check in epithelial cells during tissue development and regeneration remains to
      be fully understood. Here we show that restricting the EMT of mammary epithelial
      cells by transcription factor Ovol2 is required for proper morphogenesis and
      regeneration. Deletion of Ovol2 blocks mammary ductal morphogenesis, depletes
      stem and progenitor cell reservoirs, and leads epithelial cells to undergo EMT in
      vivo to become nonepithelial cell types. Ovol2 directly represses myriad EMT
      inducers, and its absence switches response to TGF-beta from growth arrest to
      EMT. Furthermore, forced expression of the repressor isoform of Ovol2 is able to
      reprogram metastatic breast cancer cells from a mesenchymal to an epithelial
      state. Our findings underscore the critical importance of exquisitely regulating
      epithelial plasticity in development and cancer.

PMID- 24735880
TI  - An enhancer composed of interlocking submodules controls transcriptional
      autoregulation of suppressor of hairless.
AB  - Positive autoregulation is an effective mechanism for the long-term maintenance
      of a transcription factor's expression. This strategy is widely deployed in cell
      lineages, where the autoregulatory factor controls the activity of a battery of
      genes that constitute the differentiation program of a postmitotic cell type. In
      Drosophila, the Notch pathway transcription factor Suppressor of Hairless
      activates its own expression, specifically in the socket cell of external sensory
      organs, via an autoregulatory enhancer called the ASE. Here, we show that the ASE
      is composed of several enhancer submodules, each of which can independently
      initiate weak Su(H) autoregulation. Cross-activation by these submodules is
      critical to ensure that Su(H) rises above a threshold level necessary to activate
      a maintenance submodule, which then sustains long-term Su(H) autoregulation. Our
      study reveals the use of interlinked positive-feedback loops to control
      autoregulation dynamically and provides mechanistic insight into initiation,
      establishment, and maintenance of the autoregulatory state. 

PMID- 24735881
TI  - Loss of Tet enzymes compromises proper differentiation of embryonic stem cells.
AB  - Tet enzymes (Tet1/2/3) convert 5-methylcytosine (5mC) to 5-hydroxymethylcytosine
      (5hmC) and are dynamically expressed during development. Whereas loss of
      individual Tet enzymes or combined deficiency of Tet1/2 allows for embryogenesis,
      the effect of complete loss of Tet activity and 5hmC marks in development is not
      established. We have generated Tet1/2/3 triple-knockout (TKO) mouse embryonic
      stem cells (ESCs) and examined their developmental potential. Combined deficiency
      of all three Tets depleted 5hmC and impaired ESC differentiation, as seen in
      poorly differentiated TKO embryoid bodies (EBs) and teratomas. Consistent with
      impaired differentiation, TKO ESCs contributed poorly to chimeric embryos, a
      defect rescued by Tet1 reexpression, and could not support embryonic development.
      Global gene-expression and methylome analyses of TKO EBs revealed promoter
      hypermethylation and deregulation of genes implicated in embryonic development
      and differentiation. These findings suggest a requirement for Tet- and 5hmC
      mediated DNA demethylation in proper regulation of gene expression during ESC
      differentiation and development.

PMID- 24735882
TI  - The value of soluble transferrin receptor and hepcidin in the assessment of iron
      status in children with cystic fibrosis.
AB  - BACKGROUND: The value of ferritin in the diagnosis of iron deficiency is limited
      in patients with CF since it increases in the presence of inflammation. We
      hypothesized that the soluble transferrin receptor (sTfR) and hepcidin may
      provide more information than ferritin in assessing iron status in children with
      CF. METHODS: We analyzed sTfR and hepcidin in relation to conventional iron
      status indicators in 49 children with CF. RESULTS: We found no differences in
      sTfR concentration between children with and those without ID. sTfR
      concentrations were within the normal range in all children. Hepcidin
      concentrations were low, and concentrations below the limit of detection were
      observed in 25% of the clinically stable children. CONCLUSION: The sTfR is not
      useful to determine the iron status in this population, whereas hepcidin might
      serve as an early indicator of deficient iron stores in children with CF.

PMID- 24735883
TI  - The impact of antibiotics on growth in children in low and middle income
      countries: systematic review and meta-analysis of randomised controlled trials.
AB  - OBJECTIVES: To determine whether antibiotic treatment leads to improvements in
      growth in prepubertal children in low and middle income countries, to determine
      the magnitude of improvements in growth, and to identify moderators of this
      treatment effect. DESIGN: Systematic review and meta-analysis. DATA SOURCES:
      Medline, Embase, Scopus, the Cochrane central register of controlled trials, and
      Web of Science. STUDY SELECTION: Randomised controlled trials conducted in low or
      middle income countries in which an orally administered antibacterial agent was
      allocated by randomisation or minimisation and growth was measured as an outcome.
      Participants aged 1 month to 12 years were included. Control was placebo or non
      antimicrobial intervention. RESULTS: Data were pooled from 10 randomised
      controlled trials representing 4316 children, across a variety of antibiotics,
      indications for treatment, treatment regimens, and countries. In random effects
      models, antibiotic use increased height by 0.04 cm/month (95% confidence interval
      0.00 to 0.07) and weight by 23.8 g/month (95% confidence interval 4.3 to 43.3).
      After adjusting for age, effects on height were larger in younger populations and
      effects on weight were larger in African studies compared with other regions.
      CONCLUSION: Antibiotics have a growth promoting effect in prepubertal children in
      low and middle income countries. This effect was more pronounced for ponderal
      than for linear growth. The antibiotic growth promoting effect may be mediated by
      treatment of clinical or subclinical infections or possibly by modulation of the
      intestinal microbiota. Better definition of the mechanisms underlying this effect
      will be important to inform optimal and safe approaches to achieving healthy
      growth in vulnerable populations.

PMID- 24735885
TI  - Effects of PYY3-36 and GLP-1 on energy intake, energy expenditure, and appetite
      in overweight men.
AB  - Our aim was to examine the effects of GLP-1 and PYY3-36, separately and in
      combination, on energy intake, energy expenditure, appetite sensations, glucose
      and fat metabolism, ghrelin, and vital signs in healthy overweight men. Twenty
      five healthy male subjects participated in this randomized, double-blinded,
      placebo-controlled, four-arm crossover study (BMI 29 +/- 3 kg/m(2), age 33 +/- 9
      yr). On separate days they received a 150-min intravenous infusion of 1) 0.8
      pmol.kg(-1).min(-1) PYY3-36, 2) 1.0 pmol.kg(-1).min(-1) GLP-1, 3) GLP-1 + PYY3
      36, or 4) placebo. Ad libitum energy intake was assessed during the final 30 min.
      Measurements of appetite sensations, energy expenditure and fat oxidation, vital
      signs, and blood variables were collected throughout the infusion period. No
      effect on energy intake was found after monoinfusions of PYY3-36 (-4.2 +/- 4.8%,
      P = 0.8) or GLP-1 (-3.0 +/- 4.5%, P = 0.9). However, the coinfusion reduced
      energy intake compared with placebo (-30.4 +/- 6.5%, P < 0.0001) and more than
      the sum of the monoinfusions (P < 0.001), demonstrating a synergistic effect.
      Coinfusion slightly increased sensation of nausea (P < 0.05), but this effect
      could not explain the effect on energy intake. A decrease in plasma ghrelin was
      found after all treatments compared with placebo (all P < 0.05); however,
      infusions of GLP-1 + PYY3-36 resulted in an additional decrease compared with the
      monoinfusions (both P < 0.01). We conclude that coinfusion of GLP-1 and PYY3-36
      exerted a synergistic effect on energy intake. The satiating effect of the meal
      was enhanced by GLP-1 and PYY3-36 in combination compared with placebo.
      Coinfusion was accompanied by slightly increased nausea and a decrease in plasma
      ghrelin, but neither of these factors could explain the reduction in energy
      intake. 

PMID- 24735884
TI  - Hepatic mitochondrial and ER stress induced by defective PPARalpha signaling in
      the pathogenesis of hepatic steatosis.
AB  - Emerging evidence demonstrates a close interplay between disturbances in
      mitochondrial function and ER homeostasis in the development of the metabolic
      syndrome. The present investigation sought to advance our understanding of the
      communication between mitochondrial dysfunction and ER stress in the onset of
      hepatic steatosis in male rodents with defective peroxisome proliferator
      activated receptor-alpha (PPARalpha) signaling. Genetic depletion of PPARalpha or
      perturbation of PPARalpha signaling by high-fructose diet compromised the
      functional activity of metabolic enzymes involved in mitochondrial fatty acid
      beta-oxidation and induced hepatic mitochondrial stress in rats and mice.
      Inhibition of PPARalpha activity further enhanced the expression of
      apolipoprotein B (apoB) mRNA and protein, which was associated with reduced mRNA
      expression of the sarco/endoplasmic reticulum calcium ATPase (SERCA), the
      induction of hepatic ER stress, and hepatic steatosis. Restoration of PPARalpha
      activity recovered the metabolic function of the mitochondria and ER, alleviated
      systemic hypertriglyceridemia, and improved hepatic steatosis. These findings
      unveil novel roles for PPARalpha in mediating stress signals between hepatic
      subcellular stress-responding machinery and in the onset of hepatic steatosis
      under conditions of metabolic stress. 

PMID- 24735886
TI  - Endothelial cells respond to hyperglycemia by increasing the LPL transporter
      GPIHBP1.
AB  - In diabetes, when glucose uptake and oxidation are impaired, the heart is
      compelled to use fatty acid (FA) almost exclusively for ATP. The vascular content
      of lipoprotein lipase (LPL), the rate-limiting enzyme that determines circulating
      triglyceride clearance, is largely responsible for this FA delivery and increases
      following diabetes. Glycosylphosphatidylinositol-anchored high-density
      lipoprotein-binding protein [GPIHBP1; a protein expressed abundantly in the heart
      in endothelial cells (EC)] collects LPL from the interstitial space and transfers
      it across ECs onto the luminal binding sites of these cells, where the enzyme is
      functional. We tested whether ECs respond to hyperglycemia by increasing GPIHBP1.
      Streptozotocin diabetes increased cardiac LPL activity and GPIHBP1 gene and
      protein expression. The increased LPL and GPIHBP1 were located at the capillary
      lumen. In vitro, passaging EC caused a loss of GPIHBP1, which could be induced on
      exposure to increasing concentrations of glucose. The high-glucose-induced
      GPIHBP1 increased LPL shuttling across EC monolayers. GPIHBP1 expression was
      linked to the EC content of heparanase. Moreover, active heparanase increased
      GPIHBP1 gene and protein expression. Both ECs and myocyte heparan sulfate
      proteoglycan-bound platelet-derived growth factor (PDGF) released by heparanase
      caused augmentation of GPIHBP1. Overall, our data suggest that this protein
      "ensemble" (heparanase-PDGF-GPIHBP1) cooperates in the diabetic heart to regulate
      FA delivery and utilization by the cardiomyocytes. Interrupting this axis may be
      a novel therapeutic strategy to restore metabolic equilibrium, curb lipotoxicity,
      and help prevent or delay heart dysfunction that is characteristic of diabetes. 

PMID- 24735887
TI  - Effects of hyperandrogenemia and increased adiposity on reproductive and
      metabolic parameters in young adult female monkeys.
AB  - Many patients with hyperandrogenemia are overweight or obese, which exacerbates
      morbidities associated with polycystic ovary syndrome (PCOS). To examine the
      ability of testosterone (T) to generate PCOS-like symptoms, monkeys received T or
      cholesterol (control) implants (n = 6/group) beginning prepubertally. As
      previously reported, T-treated animals had increased neuroendocrine drive to the
      reproductive axis [increased luteinizing hormone (LH) pulse frequency] at 5 yr,
      without remarkable changes in ovarian or metabolic features. To examine the
      combined effects of T and obesity, at 5.5 yr (human equivalent age: 17 yr),
      monkeys were placed on a high-calorie, high-fat diet typical of Western cultures
      [Western style diet (WSD)], which increased body fat from <2% (pre-WSD) to 15-19%
      (14 mo WSD). By 6 mo on WSD, LH pulse frequency in the controls increased to that
      of T-treated animals, whereas LH pulse amplitude decreased in both groups and
      remained low. The numbers of antral follicles present during the early follicular
      phase increased in both groups on the WSD, but maximal follicular size decreased
      by 50%. During the late follicular phase, T-treated females had greater numbers
      of small antral follicles than controls. T-treated monkeys also had lower
      progesterone during the luteal phase of the menstrual cycle. Although fasting
      insulin did not vary between groups, T-treated animals had decreased insulin
      sensitivity after 1 yr on WSD. Thus, while WSD consumption alone led to some
      features characteristic of PCOS, T + WSD caused a more severe phenotype with
      regard to insulin insensitivity, increased numbers of antral follicles at
      midcycle, and decreased circulating luteal phase progesterone levels. 

PMID- 24735889
TI  - Glucose hypometabolism is highly localized, but lower cortical thickness and
      brain atrophy are widespread in cognitively normal older adults.
AB  - Several studies have suggested that glucose hypometabolism may be present in
      specific brain regions in cognitively normal older adults and could contribute to
      the risk of subsequent cognitive decline. However, certain methodological
      shortcomings, including a lack of partial volume effect (PVE) correction or
      insufficient cognitive testing, confound the interpretation of most studies on
      this topic. We combined [(18)F]fluorodeoxyglucose ([(18)F]FDG) positron emission
      tomography (PET) and magnetic resonance (MR) imaging to quantify cerebral
      metabolic rate of glucose (CMRg) as well as cortical volume and thickness in 43
      anatomically defined brain regions from a group of cognitively normal younger (25
      +/- 3 yr old; n = 25) and older adults (71 +/- 9 yr old; n = 31). After
      correcting for PVE, we observed 11-17% lower CMRg in three specific brain regions
      of the older group: the superior frontal cortex, the caudal middle frontal
      cortex, and the caudate (P <= 0.01 false discovery rate-corrected). In the older
      group, cortical volumes and cortical thickness were 13-33 and 7-18% lower,
      respectively, in multiple brain regions (P <= 0.01 FDR correction). There were no
      differences in CMRg between individuals who were or were not prescribed
      antihypertensive medication. There were no significant correlations between CMRg
      and cognitive performance or metabolic parameters measured in fasting plasma. We
      conclude that highly localized glucose hypometabolism and widespread cortical
      thinning and atrophy can be present in older adults who are cognitively normal,
      as assessed using age-normed neuropsychological testing measures. 

PMID- 24735888
TI  - Long-lived crowded-litter mice exhibit lasting effects on insulin sensitivity and
      energy homeostasis.
AB  - The action of nutrients on early postnatal growth can influence mammalian aging
      and longevity. Recent work has demonstrated that limiting nutrient availability
      in the first 3 wk of life [by increasing the number of pups in the crowded-litter
      (CL) model] leads to extension of mean and maximal lifespan in genetically normal
      mice. In this study, we aimed to characterize the impact of early-life nutrient
      intervention on glucose metabolism and energy homeostasis in CL mice. In our
      study, we used mice from litters supplemented to 12 or 15 pups and compared those
      to control litters limited to eight pups. At weaning and then throughout adult
      life, CL mice are significantly leaner and consume more oxygen relative to
      control mice. At 6 mo of age, CL mice had low fasting leptin concentrations, and
      low-dose leptin injections reduced body weight and food intake more in CL female
      mice than in controls. At 22 mo, CL female mice also have smaller adipocytes
      compared with controls. Glucose and insulin tolerance tests show an increase in
      insulin sensitivity in 6 mo old CL male mice, and females become more insulin
      sensitive later in life. Furthermore, beta-cell mass was significantly reduced in
      the CL male mice and was associated with reduction in beta-cell proliferation
      rate in these mice. Together, these data show that early-life nutrient
      intervention has a significant lifelong effect on metabolic characteristics that
      may contribute to the increased lifespan of CL mice. 

PMID- 24735890
TI  - Inhibition of connexin 36 hemichannels by glucose contributes to the stimulation
      of insulin secretion.
AB  - The existence of functional connexin36 (Cx36) hemichannels in beta-cells was
      investigated in pancreatic islets of rat and wild-type (Cx36(+/+)), monoallelic
      (Cx36(+/-)), and biallelic (Cx36(-/-)) knockout mice. Hemichannel opening by KCl
      depolarization was studied by measuring ATP release and changes of intracellular
      ATP (ADP). Cx36(+/+) islets lost ATP after depolarization with 70 mM KCl at 5 mM
      glucose; ATP loss was prevented by 8 and 20 mM glucose or 50 MUM mefloquine
      (connexin inhibitor). ATP content was higher in Cx36(-/-) than Cx36(+/+) islets
      and was not decreased by KCl depolarization; Cx36(+/-) islets showed values
      between that of control and homozygous islets. Five minimolar extracellular ATP
      increased ATP content and ATP/ADP ratio and induced a biphasic insulin secretion
      in depolarized Cx36(+/+) and Cx36(+/-) but not Cx36(-/-) islets. Cx36
      hemichannels expressed in oocytes opened upon depolarization of membrane
      potential, and their activation was inhibited by mefloquine and glucose (IC50 ~8
      mM). It is postulated that glucose-induced inhibition of Cx36 hemichannels in
      islet beta-cells might avoid depolarization-induced ATP loss, allowing an optimum
      increase of the ATP/ADP ratio by sugar metabolism and a biphasic stimulation of
      insulin secretion. Gradual suppression of glucose-induced insulin release in
      Cx36(+/-) and Cx36(-/-) islets confirms that Cx36 gap junction channels are
      necessary for a full secretory stimulation and might account for the glucose
      intolerance observed in mice with defective Cx36 expression. Mefloquine targeting
      of Cx36 on both gap junctions and hemichannels also suppresses glucose-stimulated
      secretion. By contrast, glucose stimulation of insulin secretion requires Cx36
      hemichannels' closure but keeping gap junction channels opened.

PMID- 24735891
TI  - Coinjection of CCK and leptin reduces food intake via increased CART/TRH and
      reduced AMPK phosphorylation in the hypothalamus.
AB  - CCK and leptin are anorectic hormones produced in the small intestine and white
      adipose tissue, respectively. Investigating how these hormones act together as an
      integrated anorectic signal is important for elucidating the mechanisms by which
      energy balance is maintained. We found here that coadministration of subthreshold
      CCK and leptin, which individually have no effect on feeding, dramatically
      reduced food intake in rats. Phosphorylation of AMP-activated protein kinase
      (AMPK) in the hypothalamus significantly decreased after coinjection of CCK and
      leptin. In addition, coadministration of these hormones significantly increased
      mRNA levels of anorectic cocaine- and amphetamine-regulated transcript (CART) and
      thyrotropin-releasing hormone (TRH) in the hypothalamus. The interactive effect
      of CCK and leptin on food intake was abolished by intracerebroventricular
      preadministration of the AMPK activator AICAR or anti-CART/anti-TRH antibodies.
      These findings indicate that coinjection of CCK and leptin reduces food intake
      via reduced AMPK phosphorylation and increased CART/TRH in the hypothalamus.
      Furthermore, by using midbrain-transected rats, we investigated the role of the
      neural pathway from the hindbrain to the hypothalamus in the interaction of CCK
      and leptin to reduce food intake. Food intake reduction induced by coinjection of
      CCK and leptin was blocked in midbrain-transected rats. Therefore, the neural
      pathway from hindbrain to hypothalamus plays an important role in transmitting
      the anorectic signals provided by coinjection of CCK and leptin. Our findings
      give further insight into the mechanisms of feeding and energy balance. 

PMID- 24735892
TI  - Neuronostatin inhibits glucose-stimulated insulin secretion via direct action on
      the pancreatic alpha-cell.
AB  - Neuronostatin is a recently described peptide hormone encoded by the somatostatin
      gene. We previously showed that intraperitoneal injection of neuronostatin into
      mice resulted in c-Jun accumulation in pancreatic islets in a pattern consistent
      with the activation of glucagon-producing alpha-cells. We therefore hypothesized
      that neuronostatin could influence glucose homeostasis via a direct effect on the
      alpha-cell. Neuronostatin enhanced low-glucose-induced glucagon release in
      isolated rat islets and in the immortalized alpha-cell line alphaTC1-9.
      Furthermore, incubation with neuronostatin led to an increase in transcription of
      glucagon mRNA, as determined by RT-PCR. Neuronostatin also inhibited glucose
      stimulated insulin secretion from isolated islets. However, neuronostatin did not
      alter insulin release from the beta-cell line INS 832/13, indicating that the
      effect of neuronostatin on insulin secretion may be secondary to a direct action
      on the alpha-cell. In agreement with our in vitro data, intra-arterial infusion
      of neuronostatin in male rats delayed glucose disposal and inhibited insulin
      release during a glucose challenge. These studies suggest that neuronostatin
      participates in maintaining glucose homeostasis through cell-cell interactions
      between alpha-cells and beta-cells in the endocrine pancreas, leading to
      attenuation in insulin secretion. 

PMID- 24735893
TI  - Intraoperative ultrasound in conservative surgery for non-palpable breast cancer
      after neoadjuvant chemotherapy.
AB  - AIMS: A complete clinical response after neoadjuvant chemotherapy (NACT) in
      breast cancer patients hinders the localization of the residual lesion and the
      removal of a minimum amount of breast tissue. The aim of the present work is to
      report our single-centre experience with intraoperative ultrasound-guided (IOUS)
      excision performed by surgeons in these patients. PATIENTS AND METHODS: From
      January 2008 to December 2012, IOUS excisions were performed on 58 patients with
      a previous intralesional ultrasound-detectable metallic marker and non-palpable
      breast cancer after NACT. The specimen margins were estimated by ultrasonography
      and macroscopic pathologic examination. Successful lesion removal, specimen
      weight, and analysis of the results as regards margins were evaluated, and the
      need for breast-conserving re-excision and mastectomy was considered. RESULTS:
      After NACT the average ultrasound/mammography and MRI diameters were 11.7 mm (0
      30) and 9.1 mm (0-40) respectively. In all cases, the residual lesion or tissue
      around the marker was removed. The average weight of the specimens was 26.4 g (6
      84), being lower in cases of complete response according to ultrasound (p <
      0.05). In 4 patients (6.8%), breast-conserving re-excision was carried out, and
      in 3 patients (5.2%) a secondary mastectomy was performed, two of which had
      invasive lobular carcinoma. CONCLUSIONS: The emplacement of a readily
      echodetectable metal marker before NACT makes IOUS excision feasible in an
      increasing number of complete clinical responses, with the excision of small
      amounts of breast tissue and a high percentage of conservative breast surgery.
      This technique requires surgeons to be trained, but has the advantage of a
      reduced use of other hospital services, better planning of operating theatres,
      and less discomfort for patients, which means that it is attractive and indeed
      recommendable.

PMID- 24735894
TI  - Elimination of warm ischemia using the Ice Bag Technique does not decrease
      delayed graft function.
AB  - BACKGROUND: Warm ischemic time (WIT) in kidney transplantation has significant
      effects on graft survival, function, and postoperative morbidity. We utilized the
      Ice Bag Technique (IBT) to determine if eliminating WIT would decrease the
      incidence and length of delayed graft function (DGF) in our cohort. METHODS: We
      conducted a prospective study of 150 kidney transplants. We compared the
      elimination of WIT with IBT to traditional methods. Data was analyzed using non
      parametric statistical tests. RESULTS: 66 of the 134 patients underwent
      transplantation using IBT. 28 right kidneys, 34 left kidneys, and 4 dual kidneys
      were implanted successfully. Patients with a body mass index (BMI) as high as 41
      were transplanted. Kidneys with up to three arteries and two veins, and kidneys
      up to 15.5 by 9 cm in size were safely transplanted into either iliac fossa.
      Despite the complete elimination of WIT, there was no difference in DGF, length
      of DGF, length of stay graft rejection, graft survival, patient survival, or
      wound or urologic complications between groups (p > 0.05). CONCLUSIONS: The
      elimination of warm ischemic time using the IBT does not appear to reduce the
      incidence or length of DGF in this cohort. The technique may be useful for cases
      with prolonged anastomosis time (AT), but further studies with larger cohorts are
      required to determine whether it decreases DGF.

PMID- 24735895
TI  - [The different manifestations of pulmonary aspergillosis: multidetector computed
      tomography findings].
AB  - Pulmonary aspergillosis is a fungal infection usually caused by inhaling
      Aspergillus fumigatus spores. However, when we talk about aspergillosis, we
      normally refer to the spectrum of clinical and radiological findings that depend
      directly on the patient's immune status, on the prior existence of lung disease,
      and on the virulence of the infective organism. There are four types of pulmonary
      aspergillosis (aspergilloma, allergic bronchopulmonary aspergillosis, chronic
      necrotizing pulmonary aspergillosis, and invasive aspergillosis), and each type
      has its own distinct radiologic findings. We review the signs of pulmonary
      aspergillosis on multidetector computed tomography and we correlate them with
      patients' symptoms and immune responses. Likewise, we discuss the differential
      diagnoses. 

PMID- 24735896
TI  - [Radiological findings of a primary middle-ear lymphoma in a 8-year-old boy].

PMID- 24735897
TI  - Phenotypic and genotypic background underlying variations in fatty acid
      composition and sensory parameters in European bovine breeds.
AB  - BACKGROUND: Consuming moderate amounts of lean red meat as part of a balanced
      diet valuably contributes to intakes of essential nutrients. In this study, we
      merged phenotypic and genotypic information to characterize the variation in
      lipid profile and sensory parameters and to represent the diversity among 15
      cattle populations. Correlations between fat content, organoleptic
      characteristics and lipid profiles were also investigated. METHODS: A sample of
      436 largely unrelated purebred bulls belonging to 15 breeds and reared under
      comparable management conditions was analyzed. Phenotypic data -including fatness
      score, fat percentage, individual fatty acids (FA) profiles and sensory panel
      tests- and genotypic information from 11 polymorphisms was used. RESULTS: The
      correlation coefficients between muscle total lipid measurements and absolute vs.
      relative amounts of polyunsaturated FA (PUFA) were in opposite directions.
      Increasing carcass fat leads to an increasing amount of FAs in triglycerides, but
      at the same time the relative amount of PUFAs is decreasing, which is in
      concordance with the negative correlation obtained here between the percentage of
      PUFA and fat measurements, as well as the weaker correlation between total
      phospholipids and total lipid muscle content compared with neutral lipids.
      Concerning organoleptic characteristics, a negative correlation between flavour
      scores and the percentage of total PUFA, particularly to n-6 fraction, was found.
      The correlation between juiciness and texture is higher than with flavour scores.
      The distribution of SNPs plotted by principal components analysis (PCA) mainly
      reflects their known trait associations, although influenced by their specific
      breed allele frequencies. CONCLUSIONS: The results presented here help to
      understand the phenotypic and genotypic background underlying variations in FA
      composition and sensory parameters between breeds. The wide range of traits and
      breeds studied, along with the genotypic information on polymorphisms previously
      associated with different lipid traits, provide a broad characterization of beef
      meat, which allows giving a better response to the variety of consumers'
      preferences. Also, the development and implementation of low-density SNP panels
      with predictive value for economically important traits, such as those summarized
      here, may be used to improve production efficiency and meat quality in the beef
      industry.

PMID- 24735898
TI  - Cost-effectiveness analysis of main diagnosis tools in women with overactive
      bladder. Clinical history, micturition diary and urodynamic study.
AB  - OBJECTIVES: The aim of the present clinical research is to analyze, in the light
      of the best scientific evidence, the performance and the cost of the main
      diagnostic tools for overactive bladder (OAB). METHODS: It is an exploratory
      transversal study in which 199 women diagnosed of OAB between 2006 and 2008 were
      selected and underwent to following prospective analyses: physical examination,
      urine analysis, micturition diary (MD) and urodynamic study (UDS). A percentage
      of 80% was assumed as highly sensitive and a diagnostic difference among tests of
      10% would be considered clinically relevant. Tests' sensitivity for diagnosis of
      OAB was statistically established by two ways: isolated and combined. Besides,
      the direct and indirect costs of these tests performance were conducted. Cost
      effectiveness study of clinical history (CH), MD and US for the diagnosis of OAB
      was performed. RESULTS: Overall sensitivity for OAB diagnosis is low for the 3
      tests used in isolated way, whilst the combination of any two tests shows good
      overall sensitivity. The combination of CH and MD has appeared as the most cost
      effective alternative to OAB diagnosis. CONCLUSIONS: For OAB diagnosis, CH-DM
      combination shows the same sensitivity than the association of either of them
      with the UDS, but unlike to these, it shows the lowest cost.

PMID- 24735899
TI  - Individual late-life fecundity plateaus do exist in Drosophila melanogaster and
      are very common at old age.
AB  - Several authors have discussed the existence of late-life fecundity plateaus in
      Drosophila melanogaster. However, all these studies have pooled flies to show
      such plateaus. Here, we have reanalyzed previously published fecundity results to
      know whether these plateaus exist at the individual level. We found that these
      plateaus are observed in ca 20% of females and in more than 50% if only the
      longer-lived flies are taken into account. We conclude that late-life fecundity
      plateaus are not a rare phenomenon when considering a whole cohort of flies and
      are very common in oldest flies. 

PMID- 24735901
TI  - Editorial overview: Vaccines: Vaccines for infectious diseases: are we there yet?

PMID- 24735900
TI  - Clinical spectrum of females with HCCS mutation: from no clinical signs to a
      neonatal lethal form of the microphthalmia with linear skin defects (MLS)
      syndrome.
AB  - BACKGROUND: Segmental Xp22.2 monosomy or a heterozygous HCCS mutation is
      associated with the microphthalmia with linear skin defects (MLS) or MIDAS
      (microphthalmia, dermal aplasia, and sclerocornea) syndrome, an X-linked disorder
      with male lethality. HCCS encodes the holocytochrome c-type synthase involved in
      mitochondrial oxidative phosphorylation (OXPHOS) and programmed cell death.
      METHODS: We characterized the X-chromosomal abnormality encompassing HCCS or an
      intragenic mutation in this gene in six new female patients with an MLS phenotype
      by cytogenetic analysis, fluorescence in situ hybridization, sequencing, and
      quantitative real-time PCR. The X chromosome inactivation (XCI) pattern was
      determined and clinical data of the patients were reviewed. RESULTS: Two terminal
      Xp deletions of >= 11.2 Mb, two submicroscopic copy number losses, one of ~850 kb
      and one of >= 3 Mb, all covering HCCS, 1 nonsense, and one mosaic 2-bp deletion
      in HCCS are reported. All females had a completely (>98:2) or slightly skewed
      (82:18) XCI pattern. The most consistent clinical features were
      microphthalmia/anophthalmia and sclerocornea/corneal opacity in all patients and
      congenital linear skin defects in 4/6. Additional manifestations included various
      ocular anomalies, cardiac defects, brain imaging abnormalities, microcephaly,
      postnatal growth retardation, and facial dysmorphism. However, no obvious
      clinical sign was observed in three female carriers who were relatives of one
      patient. CONCLUSION: Our findings showed a wide phenotypic spectrum ranging from
      asymptomatic females with an HCCS mutation to patients with a neonatal lethal MLS
      form. Somatic mosaicism and the different ability of embryonic cells to cope with
      an OXPHOS defect and/or enhanced cell death upon HCCS deficiency likely underlie
      the great variability in phenotypes.

PMID- 24735902
TI  - Predict protein structural class for low-similarity sequences by evolutionary
      difference information into the general form of Chou's pseudo amino acid
      composition.
AB  - Knowledge of protein structural class plays an important role in characterizing
      the overall folding type of a given protein. At present, it is still a challenge
      to extract sequence information solely using protein sequence for protein
      structural class prediction with low similarity sequence in the current
      computational biology. In this study, a novel sequence representation method is
      proposed based on position specific scoring matrix for protein structural class
      prediction. By defined evolutionary difference formula, varying length proteins
      are expressed as uniform dimensional vectors, which can represent evolutionary
      difference information between the adjacent residues of a given protein. To
      perform and evaluate the proposed method, support vector machine and jackknife
      tests are employed on three widely used datasets, 25PDB, 1189 and 640 datasets
      with sequence similarity lower than 25%, 40% and 25%, respectively. Comparison of
      our results with the previous methods shows that our method may provide a
      promising method to predict protein structural class especially for low
      similarity sequences. 

PMID- 24735903
TI  - Multifocality and recurrence risk: a quantitative model of field cancerization.
AB  - Primary tumors often emerge within genetically altered fields of premalignant
      cells that appear histologically normal but have a high chance of progression to
      malignancy. Clinical observations have suggested that these premalignant fields
      pose high risks for emergence of recurrent tumors if left behind after surgical
      removal of the primary tumor. In this work, we develop a spatio-temporal
      stochastic model of epithelial carcinogenesis, combining cellular dynamics with a
      general framework for multi-stage genetic progression to cancer. Using the model,
      we investigate how various properties of the premalignant fields depend on
      microscopic cellular properties of the tissue. In particular, we provide analytic
      results for the size-distribution of the histologically undetectable premalignant
      fields at the time of diagnosis, and investigate how the extent and the geometry
      of these fields depend upon key groups of parameters associated with the tissue
      and genetic pathways. We also derive analytical results for the relative risks of
      local vs. distant secondary tumors for different parameter regimes, a critical
      aspect for the optimal choice of post-operative therapy in carcinoma patients.
      This study contributes to a growing literature seeking to obtain a quantitative
      understanding of the spatial dynamics in cancer initiation. 

PMID- 24735904
TI  - Impact of MBR cleaning and breaching on passage of selected microorganisms and
      subsequent inactivation by free chlorine.
AB  - Membrane bioreactors (MBRs) produce better quality effluent compared to
      conventional treatment processes but they are still subjected to the same
      disinfection requirements as conventional processes by many regulatory agencies.
      A research study consisting of bench-, pilot- and full-scale studies was
      conducted to characterize effluents produced from an MBR system operating under
      routine and challenged conditions and to assess the disinfection requirements for
      these effluents. Membrane cleaning did not seem to pose a substantial risk with
      respect to passage of target microorganisms; however, the membrane under breached
      conditions (turbidity > 0.5 NTU) resulted in an increase in a total coliform
      bacterial concentration up to 8500 CFU/100 mL. Adenoviruses were always detected
      in MBR filtrate samples by PCR (method detection limit of 10(3) genome copies per
      25 MUL reaction) irrespective of the membrane cleaning or breaching status.
      Passage of MS-2 bacteriophage through a breached membrane was lower compared to
      total coliform bacteria potentially due to their lower densities in the mixed
      liquor. Despite an increase in microbial concentration, a free chlorine CT of 30
      mg-min/L was sufficient to achieve greater than 5-log removal of seeded MS-2
      bacteriophage and removal of total coliform bacteria at or below the method
      detection limit (2 CFU/100 mL) for samples with a filtrate turbidity of 1.0 NTU.
      If such lower CT were to be employed, a significant decrease in plant footprint
      and operational costs could be realized. 

PMID- 24735905
TI  - A method to relate StarTrack((r)) measurements to R50 variations in clinical
      linacs.
AB  - The relation between the data recorded with any device for the daily checking of
      the behavior of a clinical linac and the reference magnitudes to be monitored may
      be unknown. An experimental method relating the energy stability of the electron
      beam measured with StarTrack((r)) to the R50 beam quality index is proposed. The
      bending magnet current is varied producing a change in the exit energy window
      and, therefore, a modification of the R50 value. For different values of this
      current, the output data of StarTrack((r)) and the R50, obtained from depth doses
      measured in a water phantom are determined. A linear fit between both sets of
      data allows the identification of the StarTrack((r)) output that provides the
      best way to obtain the quality index R50, for each beam nominal energy. Using
      these fits, an historical datum series is used to analyze the method proposed in
      the daily quality control. The ouput data of the StarTrack((r)) and the R50
      values show a good linear correlation. It is possible to establish a methodology
      that allows the monitoring of R50 by direct use of the daily quality control data
      measured with StarTrack((r)). A method to monitor R50 in the daily quality
      control using the StarTrack((r)) device has been developed. The method may be
      applied to similar devices in which the statistical control variable does not
      show a linear behavior with R50. 

PMID- 24735906
TI  - Frequency of manuscript publication following presentation of EMS abstracts at
      national meetings.
AB  - INTRODUCTION: Specialized knowledge and a scientific body of literature are the
      foundation of the recognition of Emergency Medical Services (EMS) as a
      subspecialty within emergency medicine (EM). Emergency Medical Services research
      often is presented at national meetings and published in abstract form, but full
      publication occurs less frequently. Problem The primary goal of the study was to
      determine the rate at which EMS-related research presented at selected
      conferences went on to manuscript publication. A secondary goal was the
      determination of the time to manuscript publication. METHODS: A cross-sectional
      study of published abstracts from the 2003-2005 national meetings of the American
      College of Emergency Physicians (ACEP), Society for Academic Emergency Medicine
      (SAEM), National Association of EMS Physicians (NAEMSP), Association of Air
      Medical Services (AAMS), and the National Association of EMS Educators (NAEMSE)
      was conducted to identify EMS-related abstracts. PubMed (National Center for
      Biotechnology Information, Bethesda, Maryland USA) was searched using abstract
      title keywords and authors' names to determine if the study had been published in
      a PubMed-indexed journal in the time since presentation and abstract publication.
      RESULTS: Abstracts for the five conferences were reviewed for 2003-2005. Six
      hundred and thirty-five EMS-related abstracts met the inclusion criteria. The
      total number of EMS abstracts presented and the percent subsequently published as
      a manuscript were: SAEM 135, 53.3%; ACEP 128, 48.4%; NAEMSP 282, 42.9%; AAMS 66,
      33.3%; and NAEMSE 24, 16.7%. The overall rate of publication was 44.3%. The
      average time to publication was 22.2 months (SD = 16.5 months, range = 0-94
      months). CONCLUSION: Less than half of EMS abstracts go on to manuscript
      publication. This may represent missed opportunities for the growth of EMS as a
      subspecialty.

PMID- 24735907
TI  - Hearing outcome of early postnatal exposure to hypoxia in Sprague-Dawley rats.
AB  - Objective: To determine the effect of experimentally induced hypoxia, in the
      first 10 days of life, on physiological hearing in a Sprague-Dawley rat model.
      Methods: A prospective, controlled animal study was carried out using 22 male rat
      pups. The rats in the hypoxic group (n = 12) were reared in hypoxia for the first
      10 days of life, and subsequently reared in normoxia, while those in the control
      group (n = 10) were reared in normoxia for the duration of the experiment.
      Hearing was assessed using auditory brainstem response testing at approximately
      72 days of age. Results: The hypoxia group had higher auditory brainstem response
      thresholds for all frequencies tested (more pronounced at 16 kHz), compared with
      controls. Wave I-V inter-peak latencies were more prolonged in the hypoxic rats,
      while both groups had similar wave I latencies. Conclusion: Chronic postnatal
      hypoxia induced permanent hearing loss in this Sprague-Dawley rat model.
      Prolonged wave I-V inter-peak latencies suggested functional abnormality in the
      central auditory pathway.

PMID- 24735908
TI  - A prospective cohort study of the association between drinking water arsenic
      exposure and self-reported maternal health symptoms during pregnancy in
      Bangladesh.
AB  - BACKGROUND: Arsenic, a common groundwater pollutant, is associated with adverse
      reproductive health but few studies have examined its effect on maternal health.
      METHODS: A prospective cohort was recruited in Bangladesh from 2008-2011 (N =
      1,458). At enrollment (<16 weeks gestational age [WGA]), arsenic was measured in
      personal drinking water using inductively-coupled plasma mass spectrometry.
      Questionnaires collected health data at enrollment, at 28 WGA, and within one
      month of delivery. Adjusted odds ratios (aORs) and 95% confidence intervals (95%
      CI) for self-reported health symptoms were estimated for each arsenic quartile
      using logistic regression. RESULTS: Overall, the mean concentration of arsenic
      was 38 MUg/L (Standard deviation, 92.7 MUg/L). A total of 795 women reported one
      or more of the following symptoms during pregnancy (cold/flu/infection,
      nausea/vomiting, abdominal cramping, headache, vaginal bleeding, or swollen
      ankles). Compared to participants exposed to the lowest quartile of arsenic
      (<=0.9 MUg/L), the aOR for reporting any symptom during pregnancy was 0.62 (95%
      CI = 0.44-0.88) in the second quartile, 1.83 (95% CI = 1.25-2.69) in the third
      quartile, and 2.11 (95% CI = 1.42-3.13) in the fourth quartile where the mean
      arsenic concentration in each quartile was 1.5 MUg/L, 12.0 MUg/L and 144.7 MUg/L,
      respectively. Upon examining individual symptoms, only nausea/vomiting and
      abdominal cramping showed consistent associations with arsenic exposure. The odds
      of self-reported nausea/vomiting was 0.98 (95% CI: 0.68, 1.41), 1.52 (95% CI:
      1.05, 2.18), and 1.81 (95% CI: 1.26, 2.60) in the second, third and fourth
      quartile of arsenic relative to the lowest quartile after adjusting for age, body
      mass index, second-hand tobacco smoke exposure, educational status, parity,
      anemia, ferritin, medication usage, type of sanitation at home, and household
      income. A positive trend was also observed for abdominal cramping (P for trend
      <0.0001). A marginal negative association was observed between arsenic quartiles
      and odds of self-reported cold/flu/infection (P for trend = 0.08). No association
      was observed between arsenic and self-reported headache (P for trend = 0.19).
      CONCLUSION: Moderate exposure to arsenic contaminated drinking water early in
      pregnancy was associated with increased odds of experiencing nausea/vomiting and
      abdominal cramping. Preventing exposure to arsenic contaminated drinking water
      during pregnancy could improve maternal health.

PMID- 24735909
TI  - [Amount of sleep and changes in its patterns in children less than two years
      old].
AB  - OBJECTIVES: The aim is to study the sleep duration and the 24-hour sleep
      distribution pattern in children under 2 years-old from two different areas of
      Spain, as well as to determine the prevalence of abnormal sleep duration and the
      influence of age on this prevalence, and compare them with the already published
      data. MATERIAL AND METHODS: An observational, descriptive and cross-sectional
      study on children from two health centers: one in Castilla y Leon and the other
      in Asturias. Their parents completed the Brief Infant Sleep Questionnaire (BISQ).
      Daytime and nighttime sleep duration was assessed, with percentiles being used to
      evaluate the results. Two groups were created: one according to the age (children
      under or above 6 months), and the other according to the area. RESULTS: A total
      of 125 children were studied (73 males). The nighttime sleep duration increased
      from 8.28+/-2.06 hours to 10.43+/-1.21 hours (P=.0001) and the daytime sleep
      decreased from 4.61+/-2.66 to 1.96+/-0.79 hours (P=.0001) for children under 6
      months and above 6 months, respectively. The children from Castilla y Leon slept
      more during daytime than those from Asturias (3.91+/-2.67 vs 3.00+/-2.09 hours,
      P=.041). Nineteen children had a total sleep duration below the 2nd percentile. A
      sleep duration below normal percentiles was observed in children under 6 months
      (14/72 vs 5/53, P=.006). CONCLUSIONS: As children grow older, they substitute
      daytime sleep for nighttime sleep. Approximately 15% of the children under 2
      years-old may have changes in sleep duration, and is more common in children
      under 6 months.

PMID- 24735910
TI  - [Comparison of body temperatures in children measured using 3 different
      thermometers: tympanic, skin and digital axillary].
AB  - OBJECTIVE: To compare body temperature measurements using tympanic, skin and
      digital axillary thermometers. METHOD: Hospitalized or outpatient children from
      the General Hospital Celaya, ISSSTE Hospital Clinic and General Hospital No. 4
      IMSS, and the pediatric private service in Celaya, Guanajuato, from 1 day of life
      until 16 years old, were recruited over a one month period, after their parents
      signed the consent form. The order of each institution was selected by simple
      randomization. Body temperatures were measured in triplicate using tympanic, skin
      and digital axillary thermometers. RESULTS: The sample consisted of 554 children.
      The Pearson r between the tympanic and digital axillary thermometers was 0.57 to
      0.65, with a positive linear relationship (P<.05); between the skin and the
      digital axillary thermometers, it was between 0.47 and 0.52 with a positive
      linearrelationship (P<.05). The intra-observer Kappa for the tympanic thermometer
      was 0.86, and for the inter-observer was 0.77; for the skin thermometer it was
      0.82 and 0.67, respectively, and for the digital axillary thermometer it was 0.86
      for intra-observer reliability and 0.78 for inter -observer reliability.
      CONCLUSION: Tympanic and axillary thermometers showed better precision in
      measuring the body temperature in children than skin thermometers.

PMID- 24735911
TI  - Spatio-temporal changes in trophic categories of infaunal polychaetes near the
      four wastewater ocean outfalls on Oahu, Hawaii.
AB  - This study examines the effect of sewage discharge on benthic polychaete
      assemblages in the context of their functional trophic categories. We present
      data spanning 20 years of monitoring benthic invertebrate assemblages and
      sediment properties at all 4 primary- and secondary-treatment wastewater outfalls
      servicing Honolulu and the island of Oahu, Hawaii, USA. Samples collected within
      mandated zones of initial dilution (ZIDs) near outfall discharge sites were
      compared to samples collected at reference stations at varying distances away.
      Our findings indicate that sediment properties were not affected by the outfall
      discharge rate or distance from each ZID. The number of polychaete species in 4
      functional trophic categories (carnivore, detritivore, omnivore, and suspension
      feeder) did not change with the outfall solid loading rate or with distance from
      each ZID, thus suggesting relatively little organic enrichment. We find no
      evidence of heavy organic enrichment beyond the designated ZIDs at these 4
      wastewater outfalls. 

PMID- 24735912
TI  - Source tracking of leaky sewers: a novel approach combining fecal indicators in
      water and sediments.
AB  - In highly urbanized areas, surface water and groundwater are particularly
      vulnerable to sewer exfiltration. In this study, as an alternative to Microbial
      Source Tracking (MST) methods, we propose a new method combining microbial and
      chemical fecal indicators (Escherichia coli (E. coli)) and wastewater
      micropollutants (WWMPs) analysis both in water and sediment samples and under
      different meteorological conditions. To illustrate the use of this method,
      wastewater exfiltration and subsequent infiltration were identified and
      quantified by a three-year field study in an urban canal. The gradients of
      concentrations observed suggest that several sources of fecal contamination of
      varying intensity may be present along the canal, including feces from resident
      animal populations, contaminated surface run-off along the banks and under bridge
      crossings, release from contaminated banks, entrainment of contaminated
      sediments, and most importantly sewage exfiltration. Calculated exfiltration
      infiltration volumes varied between 0.6 and 15.7 m(3)/d per kilometer during dry
      weather, and between 1.1 and 19.5 m(3)/d per kilometer during wet weather. WWMPs
      were mainly diluted and degraded below detection limits in water. E. coli remains
      the best exfiltration indicator given a large volume of dilution and a high
      abundance in the wastewater source. WWMPs are effective for detecting cumulated
      contamination in sediments from a small volume source and are particularly
      important because E. coli on its own does not allow source tracking. 

PMID- 24735913
TI  - Emergency response in resource-poor settings: a review of a newly-implemented EMS
      system in rural Uganda.
AB  - INTRODUCTION: The goal of an Emergency Medical Services (EMS) system is to
      prevent needless death or disability from time-sensitive disease processes.
      Despite growing evidence that these processes contribute significantly to
      mortality in low- and middle- income countries (LMICs), there has been little
      focus on the development of EMS systems in poor countries. Problem The objective
      of this study was to understand the utilization pattern of a newly-implemented
      EMS system in Ruhiira, Uganda. METHODS: An EMS system based on community
      priorities was implemented in rural Uganda in 2009. Six months of ambulance logs
      were reviewed. Patient, transfer, and clinical data were extracted and analyzed.
      RESULTS: In total, 207 cases were reviewed. Out of all transfers, 66% were for
      chief complaints that were obstetric related, while 12% were related to malaria.
      Out of all activations, 77.8% were for female patients. Among men, 34% and 28%
      were related to malaria and trauma, respectively. The majority of emergency
      transfers were from district to regional hospitals, including 52% of all
      obstetric transfers, 65% of malaria transfers, and 62% of all trauma transfers.
      There was no significant difference in the call to arrival on scene time, the
      time to scene or the scene to treatment time during the day and night (P > .05).
      Cost-benefit analysis revealed a cost of $89.95 per life saved with an estimated
      $0.93/capita to establish the system and $0.09/capita/year to maintain the
      system. CONCLUSION: Contrary to current belief, EMS systems in rural Africa can
      be affordable and highly utilized, particularly for life-threatening, nontrauma
      complaints. Construction of a simple but effective EMS system is feasible,
      acceptable, and an essential component to the primary health care system of
      LMICs.

PMID- 24735914
TI  - [Sporotrichoid eruption pattern].

PMID- 24735915
TI  - A Sydney proteome story.
AB  - This is the story of the experience of a multidisciplinary group at Macquarie
      University in Sydney as we participated in, and impacted upon, major currents
      that washed through protein science as the field of Proteomics emerged. The large
      scale analysis of proteins became possible. This is not a history of the field.
      Instead we have tried to encapsulate the stimulating personal ride we had
      transiting from conventional academe, to a Major National Research Facility, to
      the formation of Proteomics company Proteome Systems Ltd. There were lots of
      blind alleys, wrong directions, but we also got some things right and our
      efforts, along with those of many other groups around the world, did change the
      face of protein science. While the transformation is by no means yet complete,
      protein science is very different from the field in the 1990s. This article is
      part of a Special Issue entitled: 20years of Proteomics in memory of Viatliano
      Pallini. Guest Editors: Luca Bini, Juan J. Calvete, Natacha Turck, Denis
      Hochstrasser and Jean-Charles Sanchez. 

PMID- 24735916
TI  - Nocturnal snoring decreases daytime baroreceptor sensitivity.
AB  - BACKGROUND: In patients with obstructive sleep apnea heart rate variability and
      baroreceptor sensitivity during night and daytime are impaired. Snoring without
      obstructive sleep apnea may already influence heart rate variability and
      baroreceptor sensitivity during daytime. METHODS: Cardiovascular daytime testing
      was performed in 11 snorers and age, BMI, and gender matched controls. Sleep
      apnea and snoring were quantified by sleep recordings. Paced breathing was
      performed during daytime with ECG, non-invasive blood pressure, and respiration
      recorded. Heart rate variability and blood pressure variability were analyzed in
      the time and frequency domain. Baroreceptor sensitivity (alpha gain) was
      calculated. RESULTS: In snorers a significant increase in high frequency systolic
      blood pressure variability (SBPV-HF) compared to control group (0.37 mm Hg(2) vs.
      0.11 mm Hg(2) for 12 breaths and 0.35 mm Hg(2) vs. 0.10 mm Hg(2) for 15 breaths)
      was demonstrated. Furthermore a lower baroreceptor sensitivity was found in
      snorers compared to controls (9.2 ms/mm Hg vs. 16.2 ms/mm Hg for 12 breaths and
      8.5 ms/mm Hg vs. 17.4 ms/mm Hg for 15 breaths per minute) using the paced
      breathing protocol. Mean heart rate was elevated in snorers as well. CONCLUSIONS:
      Snorers may have a reduced parasympathetic tone during daytime rather than an
      increased sympathetic tone.

PMID- 24735918
TI  - First isolation of border disease virus in Japan is from a pig farm with no
      ruminants.
AB  - The first isolation of border disease virus (BDV) in Japan was from a pig farm of
      the farrow-to-finishing type that kept no small ruminants or cattle. The
      infection was detected in the course of sero-surveillance for classical swine
      fever virus (CSFV) in Japan. The infected pigs had no clinical symptoms of CSFV
      or other disease; nevertheless, a high sero-positive rate of 58.5% was
      identified. A persistently infected pig with the BDV was found and suspected to
      be the cause of sero-prevalence in the farm. The isolated BDV was genetically
      close to BDV strains from New Zealand, but there was no epidemiological evidence
      concerning the route(s) of the invasion into the farm. 

PMID- 24735917
TI  - Chronic hypertension and pregnancy outcomes: systematic review and meta-analysis.
AB  - OBJECTIVE: To provide an accurate assessment of complications of pregnancy in
      women with chronic hypertension, including comparison with population pregnancy
      data (US) to inform pre-pregnancy and antenatal management strategies. DESIGN:
      Systematic review and meta-analysis. DATA SOURCES: Embase, Medline, and Web of
      Science were searched without language restrictions, from first publication until
      June 2013; the bibliographies of relevant articles and reviews were hand searched
      for additional reports. STUDY SELECTION: Studies involving pregnant women with
      chronic hypertension, including retrospective and prospective cohorts, population
      studies, and appropriate arms of randomised controlled trials, were included.
      DATA EXTRACTION: Pooled incidence for each pregnancy outcome was reported and,
      for US studies, compared with US general population incidence from the National
      Vital Statistics Report (2006). RESULTS: 55 eligible studies were identified,
      encompassing 795,221 pregnancies. Women with chronic hypertension had high pooled
      incidences of superimposed pre-eclampsia (25.9%, 95% confidence interval 21.0% to
      31.5 %), caesarean section (41.4%, 35.5% to 47.7%), preterm delivery <37 weeks'
      gestation (28.1% (22.6 to 34.4%), birth weight <2500 g (16.9%, 13.1% to 21.5%),
      neonatal unit admission (20.5%, 15.7% to 26.4%), and perinatal death (4.0%, 2.9%
      to 5.4%). However, considerable heterogeneity existed in the reported incidence
      of all outcomes (tau(2)=0.286-0.766), with a substantial range of incidences in
      individual studies around these averages; additional meta-regression did not
      identify any influential demographic factors. The incidences (the meta-analysis
      average from US studies) of adverse outcomes in women with chronic hypertension
      were compared with women from the US national population dataset and showed
      higher risks in those with chronic hypertension: relative risks were 7.7 (95%
      confidence interval 5.7 to 10.1) for superimposed pre-eclampsia compared with pre
      eclampsia, 1.3 (1.1 to 1.5) for caesarean section, 2.7 (1.9 to 3.6) for preterm
      delivery <37 weeks' gestation, 2.7 (1.9 to 3.8) for birth weight <2500 g, 3.2
      (2.2 to 4.4) for neonatal unit admission, and 4.2 (2.7 to 6.5) for perinatal
      death. CONCLUSIONS: This systematic review, reporting meta-analysed data from
      studies of pregnant women with chronic hypertension, shows that adverse outcomes
      of pregnancy are common and emphasises a need for heightened antenatal
      surveillance. A consistent strategy to study women with chronic hypertension is
      needed, as previous study designs have been diverse. These findings should inform
      counselling and contribute to optimisation of maternal health, drug treatment,
      and pre-pregnancy management in women affected by chronic hypertension.

PMID- 24735919
TI  - Genomic dark matter sheds light on EVI1-driven leukemia.
AB  - The orchestration of transcriptional programs depends on proper gene-enhancer
      pairing. While much remains to be learned about this process in normal
      development, two recent studies in Cell (Groschel and colleagues) and this issue
      of Cancer Cell (Yamazaki and colleagues) highlight how the genomic rearrangement
      of an enhancer plays a causal role in the onset of a leukemogenic program. 

PMID- 24735920
TI  - Next-generation genomic profiling of hepatocellular adenomas: a new era of
      individualized patient care.
AB  - Hepatocellular adenomas (HCAs) are clinically relevant benign liver lesions that
      commonly occur in women on hormonal contraceptives. In this issue of Cancer Cell,
      Pilati and colleagues present an integrative multi-"omics"-based analysis of HCA
      and identify recurrent genetic alterations associated with adenoma-carcinoma
      transition and new drugable targets. 

PMID- 24735921
TI  - Harnessing the hidden antitumor power of the MLL-AF4 oncogene to fight leukemia.
AB  - It is unclear whether the antiproliferative/proapoptotic activity of oncogenes
      can be pharmacologically reactivated in cancer cells. In this issue of Cancer
      Cell, Liu and colleagues report that a proteasome inhibitor reactivates an MLL
      AF4 controlled antitumor program to kill leukemia cells in an oncogene dose- and
      cell type-dependent manner. 

PMID- 24735922
TI  - Genomic profiling of hepatocellular adenomas reveals recurrent FRK-activating
      mutations and the mechanisms of malignant transformation.
AB  - Hepatocellular adenomas (HCA) are benign liver tumors predominantly developed in
      women using oral contraceptives. Here, exome sequencing identified recurrent
      somatic FRK mutations that induce constitutive kinase activity, STAT3 activation,
      and cell proliferation sensitive to Src inhibitors. We also found uncommon
      recurrent mutations activating JAK1, gp130, or beta-catenin. Chromosome copy
      number and methylation profiling revealed patterns that correlated with specific
      gene mutations and tumor phenotypes. Finally, integrative analysis of HCAs
      transformed to hepatocellular carcinoma revealed beta-catenin mutation as an
      early alteration and TERT promoter mutations as associated with the last step of
      the adenoma-carcinoma transition. In conclusion, we identified the genomic
      diversity in benign hepatocyte proliferation, several therapeutic targets, and
      the key genomic determinants of the adenoma-carcinoma transformation sequence. 

PMID- 24735923
TI  - MicroRNA-135b promotes cancer progression by acting as a downstream effector of
      oncogenic pathways in colon cancer.
AB  - MicroRNA deregulation is frequent in human colorectal cancers (CRCs), but little
      is known as to whether it represents a bystander event or actually drives tumor
      progression in vivo. We show that miR-135b overexpression is triggered in mice
      and humans by APC loss, PTEN/PI3K pathway deregulation, and SRC overexpression
      and promotes tumor transformation and progression. We show that miR-135b
      upregulation is common in sporadic and inflammatory bowel disease-associated
      human CRCs and correlates with tumor stage and poor clinical outcome. Inhibition
      of miR-135b in CRC mouse models reduces tumor growth by controlling genes
      involved in proliferation, invasion, and apoptosis. We identify miR-135b as a key
      downsteam effector of oncogenic pathways and a potential target for CRC
      treatment. 

PMID- 24735926
TI  - SnapShot: Hepatocellular carcinoma.
AB  - Hepatocellular carcinoma is the sixth most common cancer globally and the second
      most lethal cancer worldwide. This SnapShot depicts the molecular and
      morphological features of this heterogeneous disease, as well as outlines
      associated prognostic factors, current and emerging therapies, and challenges
      ahead. 

PMID- 24735924
TI  - Cancer-secreted miR-105 destroys vascular endothelial barriers to promote
      metastasis.
AB  - Cancer-secreted microRNAs (miRNAs) are emerging mediators of cancer-host
      crosstalk. Here we show that miR-105, which is characteristically expressed and
      secreted by metastatic breast cancer cells, is a potent regulator of migration
      through targeting the tight junction protein ZO-1. In endothelial monolayers,
      exosome-mediated transfer of cancer-secreted miR-105 efficiently destroys tight
      junctions and the integrity of these natural barriers against metastasis.
      Overexpression of miR-105 in nonmetastatic cancer cells induces metastasis and
      vascular permeability in distant organs, whereas inhibition of miR-105 in highly
      metastatic tumors alleviates these effects. miR-105 can be detected in the
      circulation at the premetastatic stage, and its levels in the blood and tumor are
      associated with ZO-1 expression and metastatic progression in early-stage breast
      cancer. 

PMID- 24735925
TI  - Proteasome inhibitors evoke latent tumor suppression programs in pro-B MLL
      leukemias through MLL-AF4.
AB  - Chromosomal translocations disrupting MLL generate MLL-fusion proteins that
      induce aggressive leukemias. Unexpectedly, MLL-fusion proteins are rarely
      observed at high levels, suggesting excessive MLL-fusions may be incompatible
      with a malignant phenotype. Here, we used clinical proteasome inhibitors,
      bortezomib and carfilzomib, to reduce the turnover of endogenous MLL-fusions and
      discovered that accumulated MLL-fusions induce latent, context-dependent tumor
      suppression programs. Specifically, in MLL pro-B lymphoid, but not myeloid,
      leukemias, proteasome inhibition triggers apoptosis and cell cycle arrest
      involving activation cleavage of BID by caspase-8 and upregulation of p27,
      respectively. Furthermore, proteasome inhibition conferred preliminary benefit to
      patients with MLL-AF4 leukemia. Hence, feasible strategies to treat cancer-type
      and oncogene-specific cancers can be improvised through harnessing inherent tumor
      suppression properties of individual oncogenic fusions. 

PMID- 24735927
TI  - Development and validation of a sensitive and selective LC-MS/MS method for the
      determination of trans delta-veniferin, a resveratrol dehydrodimer, in rat plasma
      and its application to pharmacokinetics and bioavailability studies.
AB  - In this study, an accurate and reliable LC-MS/MS assay was firstly developed and
      validated for the quantitative determination of trans delta-veniferin (TVN) in
      rat plasma. Chlorzoxazone was used as the internal standard (IS). After one-step
      protein precipitation with methanol, the analyte and IS were separated on an ODS
      column by gradient elution with mobile phase of acetonitrile-0.2% formic acid at
      a flow rate of 0.3mL/min. Negative electrospray ionization was performed using
      multiple reactions monitoring (MRM) mode with transitions of m/z 453.0>410.9 for
      TVN, and m/z 168.0>132.0 for IS. Good linearity (R>=0.996) was observed over the
      concentration range of 5-5000ng/mL for TVN with a lower limit of quantification
      (LLOQ) of 5ng/mL. The mean recoveries for TVN and IS were 91.05% and 96.68%,
      respectively. The intra- and inter-day precisions (RSD) were no more than 10.5%
      and accuracies (RE) were within the range of -6.3% to 2.1%. The validated method
      was suitable for quantification of TVN and successfully applied to the
      pharmacokinetic study of TVN after oral and intravenous administration to rats.
      The oral absolute bioavailability of TVN was 14.2% in rat. 

PMID- 24735928
TI  - Determination of urinary aromatic amines in smokers and nonsmokers using a MIPs
      SPE coupled with LC-MS/MS method.
AB  - Urinary aromatic amines (AAs) could be used as biomarkers for human exposure to
      AAs in cigarette smoke. A liquid chromatography-tandem mass spectrometry (LC
      MS/MS) method was developed for the determination of urinary AAs (i.e. 1
      naphthylamine (1-NA), 2-naphthylamine (2-NA), 3-aminobiphenyl (3-ABP) and 4
      aminobiphenyl (4-ABP)) in smokers and nonsmokers. A molecularly imprinted
      polymers (MIPs) solid phase extraction (SPE) cartridge was applied to purify
      urine samples and no derivatization reaction was involved. Each analytes used
      respective stable isotope internal standards, which could well compensate matrix
      effect. Lower limit of detections (LODs) for four AAs were obtained and in the
      range of 1.5-5ngL(-1). Recovery ranged from 87.7+/-4.5% to 111.3+/-6.4% and
      precision were less than 9.9%. The method was applied to analyze urine samples of
      40 smokers and 10 nonsmokers. The 24h urinary excretion amounts of total AAs were
      higher for smokers compared with nonsmokers. What's more, 1-NA, 3-ABP and 4-ABP
      excretion amounts showed significant differences (p<0.05) between smokers and
      nonsmokers. 

PMID- 24735929
TI  - Nutritional n-3 PUFAs deficiency during perinatal periods alters brain innate
      immune system and neuronal plasticity-associated genes.
AB  - Low dietary intake of the n-3 polyunsaturated fatty acids (PUFAs) is a causative
      factor of neurodevelopmental disorders. However the mechanisms linking n-3 PUFAs
      low dietary intake and neurodevelopmental disorders are poorly understood.
      Microglia, known mainly for their immune function in the injured or infected
      brain, have recently been demonstrated to play a pivotal role in regulating
      maturation of neuronal circuits during normal brain development. Disruption of
      this role during the perinatal period therefore could significantly contribute to
      psychopathologies with a neurodevelopmental neurodevelopmental component. N-3
      PUFAs, essential lipids and key structural components of neuronal membrane
      phospholipids, are highly incorporated in cell membranes during the gestation and
      lactation phase. We previously showed that in a context of perinatal n-3 PUFAs
      deficiency, accretion of these latter is decreased and this is correlated to an
      alteration of endotoxin-induced inflammatory response. We thus postulated that
      dietary n-3 PUFAs imbalance alters the activity of microglia in the developing
      brain, leading to abnormal formation of neuronal networks. We first confirmed
      that mice fed with a n-3 PUFAs deficient diet displayed decreased n-3 PUFAs
      levels in the brain at post-natal days (PND)0 and PND21. We then demonstrated
      that n-3 PUFAs deficiency altered microglia phenotype and motility in the post
      natal developing brain. This was paralleled by an increase in pro-inflammatory
      cytokines expression at PND21 and to modification of neuronal plasticity-related
      genes expression. Overall, our findings show for the first time that a dietary n
      3 PUFAs deficiency from the first day of gestation leads to the development of a
      pro-inflammatory condition in the central nervous system that may contribute to
      neurodevelopmental alterations. 

PMID- 24735930
TI  - Effects of AKT inhibitor therapy in response and resistance to BRAF inhibition in
      melanoma.
AB  - BACKGROUND: The clinical use of BRAF inhibitors for treatment of metastatic
      melanoma is limited by the development of drug resistance. In this study we
      investigated whether co-targeting the MAPK and the PI3K-AKT pathway can prevent
      emergence of resistance or provide additional growth inhibitory effects in vitro.
      METHODS: Anti-tumor effects of the combination of the BRAF inhibitor (BRAFi)
      dabrafenib and GSK2141795B (AKTi) in a panel of 23 BRAF mutated melanoma cell
      lines were evaluated on growth inhibition by an ATP-based luminescent assay, on
      cell cycle and apoptosis by flow cytometry and on cell signaling by western blot.
      Moreover, we investigated the possibilities of delaying or reversing resistance
      or achieving further growth inhibition by combining AKTi with dabrafenib and/or
      the MEK inhibitor (MEKi) trametinib by using long term cultures. RESULTS: More
      than 40% of the cell lines, including PTEN-/- and AKT mutants showed sensitivity
      to AKTi (IC50 < 1.5 MUM). The combination of dabrafenib and AKTi synergistically
      potentiated growth inhibition in the majority of cell lines with IC50 > 5 nM
      dabrafenib. Combinatorial treatment induced apoptosis only in cell lines
      sensitive to AKTi. In long term cultures of a PTEN-/- cell line, combinatorial
      treatment with the MAPK inhibitors, dabrafenib and trametinib, and AKTi markedly
      delayed the emergence of drug resistance. Moreover, combining AKTi with the MAPK
      inhibitors from the beginning provided superior growth inhibitory effects
      compared to addition of AKTi upon development of resistance to MAPK inhibitors in
      this particular cell line. CONCLUSIONS: AKTi combined with BRAFi-based therapy
      may benefit patients with tumors harboring BRAF mutations and particularly PTEN
      deletions or AKT mutations.

PMID- 24735931
TI  - Adrenal hormonal imbalance in acute intermittent porphyria patients: results of a
      case control study.
AB  - BACKGROUND: Acute Intermittent Porphyria (AIP) is a rare disease that results
      from a deficiency of hydroxymethylbilane synthase, the third enzyme of the heme
      biosynthetic pathway. AIP carriers are at risk of presenting acute life
      threatening neurovisceral attacks. The disease induces overproduction of heme
      precursors in the liver and long-lasting deregulation of metabolic networks. The
      clinical history of AIP suggests a strong endocrine influence, being
      neurovisceral attacks more common in women than in men and very rare before
      puberty. To asses the hypothesis that steroidogenesis may be modified in AIP
      patients with biochemically active disease, we undertook a comprehensive analysis
      of the urinary steroid metabolome. METHODS: A case-control study was performed by
      collecting spot morning urine from 24 AIP patients and 24 healthy controls.
      Steroids in urine were quantified by liquid chromatography-tandem mass
      spectrometry. Parent steroids (17-hydroxyprogesterone; deoxycorticosterone;
      corticoesterone; 11-dehydrocorticosterone; cortisol and cortisone) and a large
      number of metabolites (N = 55) were investigated. Correlations between the
      different steroids analyzed and biomarkers of porphyria biochemical status
      (urinary heme precursors) were also evaluated. The Mann-Whitney U test and
      Spearman's correlation with a two tailed test were used for statistical analyses.
      RESULTS: Forty-one steroids were found to be decreased in the urine of AIP
      patients (P < 0.05), the decrease being more significant for steroids with a high
      degree of hydroxylation. Remarkably, 13 cortisol metabolites presented lower
      concentrations among AIP patients (P < 0.01) whereas no significant differences
      were found in the main metabolites of cortisol precursors. Nine cortisol
      metabolites showed a significant negative correlation with heme precursors (p <
      0.05). Ratios between the main metabolites of 17-hydroxyprogesterone and cortisol
      showed positive correlations with heme-precursors (correlation coefficient >
      0.51, P < 0.01). CONCLUSIONS: Comprehensive study of the urinary steroid
      metabolome showed that AIP patients present an imbalance in adrenal
      steroidogenesis, affecting the biosynthesis of cortisol and resulting in
      decreased out-put of cortisol and metabolites. This may result from alterations
      of central origin and/or may originate in specific decreased enzymatic activity
      in the adrenal gland. An imbalance in steroidogenesis may be related to the
      maintenance of an active disease state among AIP patients.

PMID- 24735932
TI  - A FEM-based method to determine the complex material properties of piezoelectric
      disks.
AB  - Numerical simulations allow modeling piezoelectric devices and ultrasonic
      transducers. However, the accuracy in the results is limited by the precise
      knowledge of the elastic, dielectric and piezoelectric properties of the
      piezoelectric material. To introduce the energy losses, these properties can be
      represented by complex numbers, where the real part of the model essentially
      determines the resonance frequencies and the imaginary part determines the
      amplitude of each resonant mode. In this work, a method based on the Finite
      Element Method (FEM) is modified to obtain the imaginary material properties of
      piezoelectric disks. The material properties are determined from the electrical
      impedance curve of the disk, which is measured by an impedance analyzer. The
      method consists in obtaining the material properties that minimize the error
      between experimental and numerical impedance curves over a wide range of
      frequencies. The proposed methodology starts with a sensitivity analysis of each
      parameter, determining the influence of each parameter over a set of resonant
      modes. Sensitivity results are used to implement a preliminary algorithm
      approaching the solution in order to avoid the search to be trapped into a local
      minimum. The method is applied to determine the material properties of a Pz27
      disk sample from Ferroperm. The obtained properties are used to calculate the
      electrical impedance curve of the disk with a Finite Element algorithm, which is
      compared with the experimental electrical impedance curve. Additionally, the
      results were validated by comparing the numerical displacement profile with the
      displacements measured by a laser Doppler vibrometer. The comparison between the
      numerical and experimental results shows excellent agreement for both electrical
      impedance curve and for the displacement profile over the disk surface. The
      agreement between numerical and experimental displacement profiles shows that,
      although only the electrical impedance curve is considered in the adjustment
      procedure, the obtained material properties allow simulating the displacement
      amplitude accurately. 

PMID- 24735933
TI  - Correction: The composition and stability of the vaginal microbiota of normal
      pregnant women is different from that of non-pregnant women.

PMID- 24735934
TI  - Outcome of transvaginal mesh and tape removed for pain only.
AB  - PURPOSE: Because there is reluctance to operate for pain, we evaluated midterm
      outcomes of vaginal mesh and synthetic suburethral tape removed for pain as the
      only indication. MATERIALS AND METHODS: After receiving institutional review
      board approval we reviewed a prospective database of women without a neurogenic
      condition who underwent surgery for vaginal mesh or suburethral tape removal with
      a focus on pain as the single reason for removal and a minimum 6-month followup.
      The primary outcome was pain level assessed by a visual analog scale (range 0 to
      10) at baseline and at each subsequent visit with the score at the last visit
      used for analysis. Parameters evaluated included demographics, mean time to
      presentation and type of mesh or tape inserted. RESULTS: From 2005 to 2013, 123
      patients underwent surgical removal of mesh (69) and suburethral tape (54) with
      pain as the only indication. Mean followup was 35 months (range 6 to 59) in the
      tape group and 22 months (range 6 to 47) in the mesh group. The visual analog
      scale score decreased from a mean preoperative level of 7.9 to 0.9
      postoperatively (p = 0.0014) in the mesh group and from 5.3 to 1.5 (p = 0.00074)
      in the tape group. Pain-free status, considered a score of 0, was achieved in 81%
      of tape and 67% of mesh cases, respectively. No statistically significant
      difference was found between the groups. CONCLUSIONS: When pain is the only
      indication for suburethral tape or vaginal mesh removal, a significant decrease
      in the pain score can be durably expected after removal in most patients at
      midterm followup.

PMID- 24735935
TI  - Use of nephron sparing surgery and impact on survival in children with Wilms
      tumor: a SEER analysis.
AB  - PURPOSE: Nephron sparing surgery is the standard of care for many adults with
      renal tumors and has been described in some children with Wilms tumor. However,
      beyond case series the data concerning nephron sparing surgery application and
      outcomes in patients with Wilms tumor are scarce. We examined nephron sparing
      surgery outcomes and factors associated with its application in children with
      Wilms tumor. MATERIALS AND METHODS: We retrospectively reviewed the 1998 to 2010
      SEER database. We identified patients 18 years old or younger with Wilms tumor.
      Clinical, demographic and socioeconomic data were abstracted, and statistical
      analysis was performed using multivariate logistic regression (predicting use of
      nephron sparing surgery limited to unilateral tumors smaller than 15 cm) and Cox
      regression (predicting overall survival) models. RESULTS: We identified 876 boys
      and 956 girls with Wilms tumor (mean +/- SD age 3.3 +/- 2.9 years). Of these
      patients 114 (6.2%) underwent nephron sparing surgery (unilateral Wilms tumor in
      74 and bilateral in 37). Median followup was 7.1 years. Regarding procedure
      choice, nephron sparing surgery was associated with unknown lymph node status (Nx
      vs N0, p <0.001) and smaller tumor size (p <0.001). Regarding survival, only age
      (HR 1.09, p = 0.002), race (HR 2.48, p = 0.002), stage (HR 2.99, p <0.001) and
      lymph node status (HR 2.17, p = 0.001) predicted decreased overall survival.
      Survival was not significantly different between children undergoing nephron
      sparing surgery and radical nephrectomy (HR 0.79, p = 0.58). CONCLUSIONS: In
      children with Wilms tumor included in the SEER database nephron sparing surgery
      has been infrequently performed. Nephron sparing surgery application is
      associated with smaller, bilateral tumors and with omission of lymphadenectomy.
      However, there are no evident differences in application of nephron sparing
      surgery based on demographic or socioeconomic factors. Despite lymph node under
      staging, overall survival is similar between patients undergoing nephron sparing
      surgery and radical nephrectomy.

PMID- 24735936
TI  - Epididymitis: a 21-year retrospective review of presentations to an outpatient
      urology clinic.
AB  - PURPOSE: We describe patient characteristics and age distribution of epididymitis
      in an outpatient pediatric urology referral practice during a 21-year period.
      MATERIALS AND METHODS: We retrospectively reviewed all pediatric patients
      diagnosed with epididymitis or epididymo-orchitis (ICD9 604.9) either clinically
      or with the aid of scrotal ultrasound at Primary Children's Medical Center from
      1992 through 2012. Charts were reviewed to record demographic and clinical
      features, as well as radiological and laboratory data. Multiple acute episodes
      occurring in individual patients were recorded. RESULTS: A total of 252 patients
      were identified. Mean +/- SD age at first presentation was 10.92 +/- 4.08 years.
      The majority of cases occurred during the pubertal period (11 to 14 years) and
      few patients younger than 2 years were diagnosed with epididymitis (4%). A total
      of 69 boys (27.4%) experienced a second episode of epididymitis. Scrotal
      ultrasound results were consistent with epididymitis in 87.3% of cases (144 of
      165). Urine culture results were available in 38 patients and were positive in 7
      (21%). Positive urine culture was associated with an anatomical abnormality on
      followup voiding cystourethrogram (RR 5.7, 95% CI 1.37-23.4). Physical activity
      was noted as a likely precipitating factor in 23 patients and a recent urinary
      tract infection was identified in 20. CONCLUSIONS: The majority of cases of
      epididymitis occur around the time of puberty in early adolescence, with
      relatively few cases occurring during infancy. Recurrent episodes of epididymitis
      are more common than previously reported and may affect as many as a fourth of
      all boys with acute epididymitis.

PMID- 24735937
TI  - Intraurethral injection of autologous minced skeletal muscle: a simple surgical
      treatment for stress urinary incontinence.
AB  - PURPOSE: Intraurethral injection of in vitro expanded autologous skeletal muscle
      derived cells is a new regenerative therapy for stress urinary incontinence. We
      examined the efficacy and safety of a simpler alternative strategy using freshly
      harvested, minced autologous skeletal muscle tissue with its inherent content of
      regenerative cells. MATERIALS AND METHODS: A total of 20 and 15 women with
      uncomplicated and complicated stress urinary incontinence, respectively, received
      intraurethral injections of minced autologous skeletal muscle tissue and were
      followed for 1 year. Efficacy was assessed by the number of leakages in a 3-day
      diary and by ICIQ-SF scores. We calculated the rates of cure, defined as zero
      leaks in 3 days plus an ICIQ-SF score of 5 or less, and improvement, defined as
      simultaneous decreases in each outcome measure. RESULTS: Significant reductions
      were observed in each group in the mean number of leakages (p <0.01) and in ICIQ
      SF scores (p <0.001). In the uncomplicated group cure and improvement were
      observed in 25% and 63% of patients, and in the complicated group they were noted
      in 7% and 57%, respectively. No voiding dysfunction developed and only minor
      adverse events were noted. CONCLUSIONS: Intraurethral injection of minced
      autologous muscle tissue is a simple surgical procedure that appears safe and
      moderately effective in women with uncomplicated stress urinary incontinence. It
      compares well to a more complicated regenerative strategy using in vitro expanded
      muscle derived cells.

PMID- 24735938
TI  - Reassessment of prognostic heterogeneity of pT3 renal pelvic urothelial
      carcinoma: analysis in terms of proposed pT3 subclassification systems.
AB  - PURPOSE: We determined whether the 3 pT3 subclassification systems reported by
      the Asan, Cornell and Nagoya groups provide an accurate estimation of patient
      prognosis. We also determined which subclassification is most predictive of the
      heterogeneous oncological outcomes of pT3 renal pelvic urothelial carcinoma.
      MATERIALS AND METHODS: Using a Korea-Japan multi-institutional, retrospective
      database 250 pT3 renal pelvic urothelial carcinomas treated with radical
      nephroureterectomy were assigned to the 3 pT3 subcategories by tumor location and
      depth of parenchymal invasion after pathological reevaluation. Recurrence-free
      and cancer specific survival was assessed according to the 3 pT3
      subclassifications. Predictive accuracy for survival in 4 models (baseline and
      each of the 3 pT3 subclassifications) was quantified and predictive accuracy
      increments for each model were compared. RESULTS: In the baseline multivariate
      Cox regression model nodal metastasis and high grade were significant for
      survival. On multivariate analysis including the pT3 subclassifications the 3
      subclassifications remained significantly associated with survival rates. Of the
      3 pT3 subclassification systems the Cornell subclassification had the highest
      predictive accuracy for discriminating the heterogeneous prognosis of pT3 renal
      pelvic urothelial carcinoma, followed by the Nagoya subclassification. Compared
      with the baseline model adding the Cornell subclassification significantly
      increased predictive accuracy for recurrence-free survival from 0.687 to 0.742 (p
      = 0.029) and for cancer specific survival from 0.713 to 0.758 (p = 0.047).
      CONCLUSIONS: The criteria of microscopic vs macroscopic parenchymal invasion
      and/or peripelvic fat invasion provide the most accurate differential
      classification of the prognostic heterogeneity of pT3 renal pelvic urothelial
      carcinoma. Further studies should be performed to determine the need to modify
      the current pT3 renal pelvic urothelial carcinoma staging system.

PMID- 24735939
TI  - Protective effect of (-)-epigallocatechin-3-gallate against cisplatin-induced
      ototoxicity.
AB  - Objective: Ototoxicity due to cisplatin therapy interferes with treatment and
      often forces a reduction in the dosage, duration and frequency of the cisplatin
      therapy. (-)-Epigallocatechin-3-gallate is known to have the highest antioxidant
      potency among all tea catechins. This study aimed to investigate the effect of (
      )-epigallocatechin-3-gallate on cisplatin ototoxicity in an auditory cell line:
      House Ear Institute-Organ of Corti 1 cells. Methods: Cultured House Ear Institute
      Organ of Corti 1 cells were exposed to cisplatin with or without pre-treatment
      with (-)-epigallocatechin-3-gallate. Cell viability was evaluated using a 3-(4,5
      dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Hoechst 33258
      staining was used to identify cells undergoing apoptosis. Western blot analysis
      was conducted to determine whether (-)-epigallocatechin-3-gallate inhibited
      cisplatin-induced caspase activation. Intracellular reactive oxygen species
      production was examined to investigate whether (-)-epigallocatechin-3-gallate was
      capable of scavenging cisplatin-induced reactive oxygen species accumulation.
      Results: Cell viability significantly increased in cells pre-treated with (-)
      epigallocatechin-3-gallate compared with cells exposed to cisplatin alone.
      Cisplatin increased cleaved caspase-3 on Western blot analysis; however, pre
      treatment with (-)-epigallocatechin-3-gallate inhibited the expression of caspase
      3. (-)-Epigallocatechin-3-gallate attenuated reactive oxygen species production
      and apoptosis in House Ear Institute-Organ of Corti 1 cells. Conclusion: (-)
      Epigallocatechin-3-gallate protected against cisplatin cytotoxicity through anti
      apoptotic and anti-oxidative effects. Therefore, (-)-epigallocatechin-3-gallate
      could play a preventive role in cisplatin-induced ototoxicity.

PMID- 24735940
TI  - Drusen simulating optic neuropathy.

PMID- 24735941
TI  - Neurological manifestations in Erdheim-Chester disease: Two case reports.

PMID- 24735942
TI  - Diversity of bone matrix adhesion proteins modulates osteoblast attachment and
      organization of actin cytoskeleton.
AB  - Interaction of cells with extracellular matrix is an essential event for
      differentiation, proliferation and activity of osteoblasts. In bone, binding of
      osteoblasts to bone matrix is required to determine specific activities of the
      cells and to synthesize matrix bone proteins. Integrins are the major cell
      receptors involved in the cell linkage to matrix proteins such as fibronectin,
      type I collagen and vitronectin, via the RGD-sequences. In this study, cultures
      of osteoblast-like cells (Saos-2) were done on coated glass coverslips in various
      culture conditions: DMEM alone or DMEM supplemented with poly-L-lysine (PL),
      fetal calf serum (FCS), fibronectin (FN), vitronectin (VN) and type I collagen
      (Col-I). The aim of the study was to determine the specific effect of these bone
      matrix proteins on cell adherence and morphology and on the cytoskeleton status.
      Morphological characteristics of cultured cells were studied using scanning
      electron microscopy and image analysis. The heterogeneity of cytoskeleton was
      studied using fractal analysis (skyscrapers and blanket algorithms) after
      specific preparation of cells to expose the cytoskeleton. FAK and MAPK signaling
      pathways were studied by western blotting in these various culture conditions.
      Results demonstrated that cell adhesion was reduced with PL and VN after 240 min.
      After 60 min of adhesion, cytoskeleton organization was enhanced with FN, VN and
      Col-I. No difference in FAK phosphorylation was observed but MAPK phosphorylation
      was modulated by specific adhesion on extracellular proteins. These results
      indicate that culture conditions modulate cell adhesion, cytoskeleton
      organization and intracellular protein pathways according to extracellular
      proteins present for adhesion.

PMID- 24735943
TI  - A combined chemical and biological assessment of industrial contamination in an
      estuarine system in Kerala, India.
AB  - The Cochin Backwaters in India are part of the Vembanad-Kol system, which is a
      protected wetland and one of the largest estuarine ecosystems in South Asia. The
      backwaters are a major supplier of fisheries resources and are developed as
      tourist destination. Periyar River discharges into the northern arm of the system
      and receives effluents from chemical, petrochemical and metal processing
      industries which release huge amounts of wastewaters after little treatment. We
      investigated water and sediment contamination in the industrial vicinity and at
      one station further away including organic and inorganic contaminants. In total
      83 organic contaminants were found, e.g. well known priority pollutants such as
      endosulfan, hexachlorobenzene, DDT, hexachlorocyclohexane and their metabolites,
      which likely stem from the industrial manufacturing of organochlorine pesticides.
      Furthermore, several benzothiazole, dibenzylamine and dicyclohexylamine
      derivatives were detected, which indicated inputs from rubber producing
      facilities. Several of these compounds have not been reported as environmental
      contaminants so far. A comparison of organic contaminant and trace hazardous
      element concentrations in sediments with reported sediment quality guidelines
      revealed that adverse effects on benthic species are likely at all stations. The
      chemical assessment was combined with an investigation of macrobenthic diversity
      and community composition. Benthic organisms were completely lacking at the site
      with the highest trace hazardous element concentrations. Highest species numbers,
      diversity indices and abundances were recorded at the station with the greatest
      distance to the industrial area. Filter feeders were nearly completely lacking,
      probably leading to an impairment of the filter function in this area. This study
      shows that a combination of chemical and biological methods is an innovative
      approach to achieve a comprehensive characterization of industrial contamination,
      to evaluate associated risks for bottom dwelling consumers regarding sediment
      quality guidelines, and to observe related adverse effects on the benthic
      community directly in the field. 

PMID- 24735944
TI  - Transfer of real-time ultrasound video of FAST examinations from a simulated
      disaster scene via a mobile phone.
AB  - OBJECTIVE: Disaster management is a complex and difficult undertaking that may
      involve limited health care resources and evaluation of multiple victims. The
      objectives of this study were to evaluate the feasibility of real-time ultrasound
      video transmission from a simulated disaster triage location via commercially
      available video mobile phones and assess the ability of emergency physicians to
      accurately interpret the transmitted video of Focused Assessment with Sonography
      for Trauma (FAST) ultrasound examinations. METHODS: This was a prospective,
      observational study that took place at a simulated disaster scene put on for an
      Advanced Disaster Life Support (ADLS) course. The second component occurred at a
      Level I academic urban emergency department (ED) with an annual census of 78,000.
      Nineteen subjects at a simulated disaster scene were scanned using a SonoSite
      Titan ultrasound system (Bothell, Washington USA). An off-the-shelf, basic, video
      capable mobile phone was used to record each ultrasound examination; and then
      immediately transmit the videos to another mobile phone approximately 170 miles
      away. The transmitted video was received by three emergency physicians with
      hospital credentialing in emergency ultrasound. Each FAST examination video was
      assessed for pathology, such as free fluid. The reviewers graded the image
      quality and documented the overall confidence level regarding whether or not a
      complete and adequate examination was visualized. Spearman's rank correlation
      coefficient was used to examine the agreement between the reviewers and the
      sonologist who performed the ultrasound examinations. RESULTS: A total of 19
      videos were transmitted. The median time for transmission of a video was 82.5
      seconds (95% CI, 67.7 seconds-97.3 seconds). No video failed to transmit
      correctly on the first attempt. The image quality ratings for the three reviewers
      were 7.7, 7.5, and 7.4 on a 10-point Likert scale. There was a moderate agreement
      between the reviewers and sonologist in image quality rating and overall
      confidence level scores (rho = 0.6). CONCLUSIONS: Real-time portable ultrasound
      video transmission via commercially available video mobile phones from a
      simulated disaster triage location is feasible and emergency physicians were able
      to accurately interpret video of FAST ultrasound examinations.

PMID- 24735945
TI  - Myc induced replicative stress response: How to cope with it and exploit it.
AB  - Myc is a cellular oncogene frequently deregulated in cancer that has the ability
      to stimulate cellular growth by promoting a number of proliferative and pro
      survival pathways. Here we will focus on how Myc controls a number of diverse
      cellular processes that converge to ensure processivity and robustness of DNA
      synthesis, thus preventing the inherent replicative stress responses usually
      evoked by oncogenic lesions. While these processes provide cancer cells with a
      long-term proliferative advantage, they also represent cancer liabilities that
      can be exploited to devise innovative therapeutic approaches to target Myc
      overexpressing tumors. This article is part of a Special Issue entitled: Myc
      proteins in cell biology and pathology. 

PMID- 24735946
TI  - The many faces of small nucleolar RNAs.
AB  - Small nucleolar RNAs (snoRNAs) are a class of evolutionally conserved non-coding
      RNAs traditionally associated with nucleotide modifications in other RNA species.
      Acting as guides pairing with ribosomal (rRNA) and small nuclear RNAs (snRNAs),
      snoRNAs direct partner enzymes to specific sites for uridine isomerization or
      ribose methylation, thereby influencing stability, folding and protein
      interacting properties of target RNAs. In recent years, however, numerous non
      canonical functions have also been ascribed to certain members of the snoRNA
      group, ranging from regulation of mRNA editing and/or alternative splicing to
      posttranscriptional gene silencing by a yet poorly understood pathway that may
      involve microRNA-like mechanisms. While some of these intriguing snoRNAs (the so
      called orphan snoRNAs) have no sequence complementarity to rRNA or snRNA, others
      apparently display dual functionality, performing both traditional and newly
      elucidated functions. Here, we review the effects elicited by non-canonical
      snoRNA activities. 

PMID- 24735947
TI  - Risk factors for discontinuation of insulin pump therapy in pediatric and young
      adult patients.
AB  - BACKGROUND: Previous studies have shown that only a small number of pediatric and
      young adult patients discontinue pump therapy, but risk factors for
      discontinuation are unclear. OBJECTIVE: To identify characteristics of pediatric
      and young adult patients with pump therapy which are associated with
      discontinuation of treatment. SUBJECTS AND METHODS: Retrospective cohort study
      using a representative nationwide database (LRx; IMS Health) in Germany covering
      >80% of all prescriptions to members of statutory health insurances in 2008-2011.
      All patients (age group <25 years) with new prescriptions of insulin pumps were
      identified (2009-2010) and were followed for 12 months. RESULTS: Overall, 2452
      new pump users were identified, of whom 177 (7.2%) switched to other forms of
      insulin therapy within 12 months. In multivariate logistic regression, younger
      age (<6 years; reference 18 to <25 years: Odds ratio, OR, 95% CI: 0.36; 0.17
      0.74) and use of teflon needles (reference steel needles: OR, 95% CI: 0.59; 0.41
      0.83) were related to a lower odds of pump discontinuation. A non-significant
      trend was found for male sex (OR, 95% CI: 0.75; 0.52-1.08). Prescriptions of
      thyroid therapeutics (ATC H03A: OR, 95% CI: 1.79; 1.23-2.61) and antiepileptics
      (N03: OR, 95% CI: 3.14; 1.49-6.59) were significantly associated with
      discontinuation of pump therapy. CONCLUSIONS: About 93% of pediatric and young
      adult patients maintained insulin pump therapy within 12 months. Age <6 years,
      male sex and teflon needle use were associated with a lower risk of
      discontinuation. Thyroid therapy (indicating autoimmunity) and antiepileptic drug
      prescriptions were associated with a higher likelihood for discontinuation of
      insulin pump treatment.

PMID- 24735948
TI  - AKT/mTOR and c-Jun N-terminal kinase signaling pathways are required for
      chrysotile asbestos-induced autophagy.
AB  - Chrysotile asbestos is closely associated with excess mortality from pulmonary
      diseases such as lung cancer, mesothelioma, and asbestosis. Although multiple
      mechanisms in which chrysotile asbestos fibers induce pulmonary disease have been
      identified, the role of autophagy in human lung epithelial cells has not been
      examined. In this study, we evaluated whether chrysotile asbestos induces
      autophagy in A549 human lung epithelial cells and then analyzed the possible
      underlying molecular mechanism. Chrysotile asbestos induced autophagy in A549
      cells based on a series of biochemical and microscopic autophagy markers. We
      observed that asbestos increased expression of A549 cell microtubule-associated
      protein 1 light chain 3 (LC3-II), an autophagy marker, in conjunction with
      dephosphorylation of phospho-AKT, phospho-mTOR, and phospho-p70S6K. Notably,
      AKT1/AKT2 double-knockout murine embryonic fibroblasts (MEFs) had negligible
      asbestos-induced LC3-II expression, supporting a crucial role for AKT signaling.
      Chrysotile asbestos also led to the phosphorylation/activation of Jun N-terminal
      kinase (JNK) and p38 MAPK. Pharmacologic inhibition of JNK, but not p38 MAPK,
      dramatically inhibited the protein expression of LC3-II. Moreover, JNK2(-/-) MEFs
      but not JNK1(-/-) MEFs blocked LC3-II levels induced by chrysotile asbestos. In
      addition, N-acetylcysteine, an antioxidant, attenuated chrysotile asbestos
      induced dephosphorylation of P-AKT and completely abolished
      phosphorylation/activation of JNK. Finally, we demonstrated that chrysotile
      asbestos-induced apoptosis was not affected by the presence of the autophagy
      inhibitor 3-methyladenine or autophagy-related gene 5 siRNA, indicating that the
      chrysotile asbestos-induced autophagy may be adaptive rather than prosurvival.
      Our findings demonstrate that AKT/mTOR and JNK2 signaling pathways are required
      for chrysotile asbestos-induced autophagy. These data provide a mechanistic basis
      for possible future clinical applications targeting these signaling pathways in
      the management of asbestos-induced lung disease. 

PMID- 24735949
TI  - Treating severe allergic asthma with anti-IgE monoclonal antibody (omalizumab): a
      review.
AB  - Increased asthma severity is not only associated with enhanced recurrent
      hospitalization and mortality but also with higher social costs. Several cases of
      asthma are atopic in nature, with the trigger for acute asthma attacks and
      chronic worsening of inflammation being allergens inducing an immune, IgE
      mediated response. Anti-inflammatory treatments are effective for most of asthma
      patients, but there are subjects whose disease is incompletely controlled by
      inhaled or systemic corticosteroids and these patients account for about 50% of
      the healthcare costs of asthma. Omalizumab is a biological engineered, humanized
      recombinant monoclonal anti-IgE antibody developed for the treatment of allergic
      diseases and with clear efficacy in adolescent and adult patients with severe
      allergic asthma. The anti-IgE antibody inhibits IgE functions blocking free serum
      IgE and inhibiting their binding to cellular receptors. By reducing serum IgE
      levels and IgE receptor expression on inflammatory cells in the context of
      allergic cascade, omalizumab has demonstrated to be a very useful treatment of
      atopic asthma, improving quality of life of patients with severe persistent
      allergic asthma that is inadequately controlled by currently available asthma
      medications. Several trials have demonstrated that this therapy is well tolerated
      and significantly improves symptoms and disease control, reducing asthma
      exacerbations and the need to use high dosage of inhaled corticosteroids. 

PMID- 24735950
TI  - Lactate regulates myogenesis in C2C12 myoblasts in vitro.
AB  - Satellite cells (SCs) are the resident stem cells of skeletal muscle tissue which
      play a major role in muscle adaptation, e.g. as a response to physical training.
      The aim of this study was to examine the effects of an intermittent lactate (La)
      treatment on the proliferation and differentiation of C2C12 myoblasts, simulating
      a microcycle of high intensity endurance training. Furthermore, the involvement
      of reactive oxygen species (ROS) in this context was examined. C2C12 myoblasts
      were therefore repeatedly incubated for 2 h each day with 10 mM or 20 mM La
      differentiation medium (DM) and in some cases 20 mM La DM plus different
      antioxidative substances for up to 5 days. La free (0 mM) DM served as a control.
      Immunocytochemical staining, Western blot analysis and colorimetric assays were
      used to assess oxidative stress, proliferation, and differentiation. Results show
      that La induces oxidative stress, enhances cell-cycle withdrawal, and initiates
      early differentiation but delays late differentiation in a timely and dose
      dependent manner. These effects can be reversed by the addition of antioxidants
      to the La DM. We therefore conclude that La has a regulatory role in C2C12
      myogenesis via a ROS-sensitive mechanism which elicits implications for
      reassessing some aspects of training and the use of nutritional supplements.

PMID- 24735951
TI  - Phases of reprogramming.
AB  - Despite advances in the field of somatic cell reprogramming, an understanding and
      exploration of the underlying mechanisms governing this process are only recently
      emerging. It is now increasingly apparent that key sequential events correlate
      with the reprogramming process; a process previously thought to be random and
      unpredictable is now looking, to a greater extent, defined and controlled.
      Herein, we will review the key cellular and molecular events associated with the
      reprogramming process, giving an integrative and conciliatory view of the
      different studies addressing the mechanism of nuclear reprogramming. 

PMID- 24735952
TI  - Legislating thresholds for drug trafficking: a policy development case study from
      New South Wales, Australia.
AB  - BACKGROUND: Legal thresholds are used in many parts of the world to define the
      quantity of illicit drugs over which possession is deemed "trafficking" as
      opposed to "possession for personal use". There is limited knowledge about why or
      how such laws were developed. In this study we analyse the policy processes
      underpinning the introduction and expansion of the drug trafficking legal
      threshold system in New South Wales (NSW), Australia. METHODS: A critical legal
      and historical analysis was undertaken sourcing data from legislation,
      Parliamentary Hansard debates, government inquiries, police reports and research.
      A timeline of policy developments was constructed from 1970 until 2013 outlining
      key steps including threshold introduction (1970), expansion (1985), and
      wholesale revision (1988). We then critically analysed the drivers of each step
      and the roles played by formal policy actors, public opinion, research/data and
      the drug trafficking problem. RESULTS: We find evidence that while justified as a
      necessary tool for effective law enforcement of drug trafficking, their
      introduction largely preceded overt police calls for reform or actual increases
      in drug trafficking. Moreover, while the expansion from one to four thresholds
      had the intent of differentiating small from large scale traffickers, the
      quantities employed were based on government assumptions which led to "manifest
      problems" and the revision in 1988 of over 100 different quantities. Despite the
      revisions, there has remained no further formal review and new quantities for
      "legal highs" continue to be added based on assumption and an uncertain evidence
      base. CONCLUSION: The development of legal thresholds for drug trafficking in NSW
      has been arbitrary and messy. That the arbitrariness persists from 1970 until the
      present day makes it hard to conclude the thresholds have been well designed. Our
      narrative provides a platform for future policy reform.

PMID- 24735953
TI  - Reproductive characteristics in female Swedish moose (Alces alces), with emphasis
      on puberty, timing of oestrus, and mating.
AB  - BACKGROUND: The moose (Alces alces) is an intensively managed keystone species in
      Fennoscandia. Several aspects of reproduction in moose have not been fully
      elucidated, including puberty, timing of mating and oestrus, and the length of
      the oestrus period. These aspects are relevant for an adaptive management of
      moose with respect to harvest, population size, demography and environmental
      conditions. Therefore, an investigation of female moose reproduction was
      conducted during the moose-hunting period in southern Sweden from 2008 to 2011.
      RESULTS: A total of 250 reproductive organs and information on carcass weight and
      age was collected from four different hunting areas (provinces of Oland, Smaland,
      Sodermanland, and Vastergotland) in southern Sweden. The results showed that
      puberty in female moose varied with carcass weight, age, and time of season. The
      period for oestrous/mating lasted from about mid September to the beginning of
      November. CONCLUSIONS: The oestrus period (predominantly for heifers) is longer
      than previously reported and was not finished when the hunting period started.
      Sampling the uterine cervix to detect spermatozoa was a useful method to
      determine if mating had occurred. To avoid hunting of moose during oestrus, we
      suggest that the hunting period should be postponed by at least 14 days in
      southern Sweden.

PMID- 24735954
TI  - Health-related quality of life and income-related social mobility in young
      adults.
AB  - BACKGROUND: To assess the association of income-related social mobility between
      the age of 13 and 30 years on health-related quality of life among young adults.
      METHODS: In 1988-89 n = 7,673 South Australian school children aged 13 years were
      sampled with n = 4,604 children (60.0%) and n = 4,476 parents (58.3%) returning
      questionnaires. In 2005-06 n = 632 baseline study participants responded (43.0%
      of those traced and living in Adelaide). RESULTS: Multivariate regressions
      adjusting for sex, tooth brushing and smoking status at age 30 showed that
      compared to upwardly mobile persons social disadvantage was associated (p < 0.05)
      with more oral health impact (Coeff = 5.5), lower EQ-VAS health state (Coeff = 
      5.8), and worse satisfaction with life scores (Coeff = -3.5) at age 30 years,
      while downward mobility was also associated with lower satisfaction with life
      scores (Coeff = -1.3). CONCLUSIONS: Stable income-related socioeconomic
      disadvantage was associated with more oral health impact, and lower health state
      and life satisfaction, while being downwardly mobile was associated with lower
      life satisfaction at age 30 years. Persons who were upwardly mobile were similar
      in health outcomes to stable advantaged persons.

PMID- 24735955
TI  - New government in Rajasthan is accused of trying to sabotage free drug scheme.

PMID- 24735956
TI  - ET-1 plasma levels, choroidal thickness and multifocal electroretinogram in
      retinitis pigmentosa.
AB  - AIM: To assess the relationship between both photoreceptor function and choroidal
      thickness and endothelin-1 (ET-1) plasma levels in patients with early stage
      retinitis pigmentosa (RP). MAIN METHODS: We compared 24 RP patients (14 males and
      10 females), 25 to 42 years of age (mean age: 34+/-7 years) with 24 healthy
      controls (12 males and 12 females) aged between 28 and 45 years (mean 36+/-6.8
      years). All patients underwent visual field test, electroretinogram and
      multifocal-electroretinogram and choroidal thickness measurement by using
      spectral domain optical coherence tomography. KEY FINDINGS: RP patients had a
      visual acuity of 0.95, a mean defect of the visual field of -7.90+/-1.75 dB, a
      pattern standard deviation index of 6.09+/-4.22 dB and a b-wave ERG amplitude of
      45.08+/-8.24 MUV. Notably RP subjects showed significantly increased ET-1 plasma
      levels and reduced choroidal thickness compared with controls: respectively,
      2.143+/-0.258 pg/ml vs. 1.219+/-0.236 pg/ml; p<0.002 and 226.75+/-76.37 MUm vs.
      303.9+/-39.87 MUm; p<0.03. Spearman's correlation test highlighted that the
      increase of ET-1 plasma levels was related with the decrease of choroidal
      thickness (r=-0.702; p<0.023) and the increase of implicit time in both ring 2
      (r=-0.669; p<0.034) and ring 3 (r=-0.883; p<0.007) of mfERG. SIGNIFICANCE:
      Increased ET-1 plasma levels may play a key role in the impairment of retinal and
      choroidal blood flow due to the vasoconstriction induced by ET-1. This could lead
      to worsening of the abiotrophic process of the macular photoreceptors.

PMID- 24735957
TI  - Significant reversal of cardiac upregulated endothelin-1 system in a rat model of
      sepsis by landiolol hydrochloride.
AB  - AIMS: Landiolol hydrochloride, an ultra-short-acting highly cardio-selective beta
      1 blocker, has become useful for various medical problems. Recent studies have
      demonstrated that co-treatment with landiolol protects against acute lung injury
      and cardiac dysfunction in rats of lipopolysaccharide (LPS)-induced systemic
      inflammation, and was also associated with a significant reduction in serum
      levels of the inflammation mediator HMGB-1 and histological lung damage.
      Endothelin (ET)-1, a potent vasoconstrictor, has been implicated in pathogenesis
      of sepsis and sepsis-induced multiple organ dysfunction syndrome. Here, we
      investigated whether landiolol hydrochloride can play important roles in
      ameliorating LPS-induced alterations in cardiac ET system of septic rats. MAIN
      METHODS: Eight-week-old male Wistar rats were administered LPS only for 3 h and
      the rest were treated with LPS as well as with landiolol non-stop for 3 h. KEY
      FINDINGS: At 3 h after LPS (only) administration, circulatory tumor necrosis
      factor (TNF)-alpha level, blood lactate concentration and percentage of
      fractional shortening of heart were significantly increased. In addition, LPS
      induced a significant expression of various components of cardiac ET-1 system
      compared to control. Finally, treatment of LPS-administered rats with landiolol
      for 3 h normalized LPS-induced blood lactate levels and cardiac functional
      compensatory events, without altering levels of plasma TNF-alpha and ET-1. Most
      strikingly, landiolol treatment significantly normalized various components of
      cardiac ET-1 signaling system in septic rat. SIGNIFICANCE: Taken together, these
      data led us to conclude that landiolol may be cardio-protective in septic rats by
      normalizing the expression of cardiac vasoactive peptide such as ET, without
      altering the circulatory levels of inflammatory cytokines.

PMID- 24735958
TI  - Pheophytin a and chlorophyll a suppress neuroinflammatory responses in
      lipopolysaccharide and interferon-gamma-stimulated BV2 microglia.
AB  - AIMS: Microglia-mediated inflammation is associated with pathogenesis of various
      neuronal disorders. This study investigated inhibitory effects of pheophytin a
      (PP) and chlorophyll a (CP) on neuroinflammation and underlying cellular
      mechanisms in microglia cells. MAIN METHODS: BV2 murine microglia cells were
      stimulated by lipopolysaccharide (LPS, 100 ng/mL) and interferon (IFN)-gamma (10
      U/mL). The productions of nitric oxide (NO) and expressions of proinflammatory
      cytokines and chemokines were determined by ELISA and RT-PCR. Western blot and
      confocal microscopy were applied to analyze activation of transcription factors
      and mitogen activated protein kinase (MAPK). KEY FINDINGS: PP and CP
      significantly reduced the levels of NO, tumor necrosis factor (TNF)-alpha,
      interleukin (IL)-1beta, IL-6 and chemokines including macrophage inhibitory
      protein (MIP)-1alpha, macrophage chemoattractant protein (MCP)-1 and IFN-gamma
      inducible protein (IP)-10 in BV2 cells stimulated with LPS and IFN-gamma (LI).
      The nuclear expression of p65 NF-kappaB was significantly suppressed, which was
      accompanied by reduced the levels of IFN-beta, phospho-STAT-1, and interferon
      regulatory factor (IRF)-1. Activation of extracellular signal-regulated kinase
      (ERK) and c-Jun NH2-terminal kinase (JNK) but not p38 MAPK were prominently
      suppressed by PP and/or CP. SIGNIFICANCE: PP and CP may suppress inflammatory
      responses by inhibiting NF-kappaB activation and type I IFN signaling pathway.
      These result suggested that PP and CP have potential as anti-inflammatory agents
      for microglia-mediated neuroinflammatory disorders.

PMID- 24735959
TI  - Endothelin-1 activates extracellular signal-regulated kinases 1/2 via
      transactivation of platelet-derived growth factor receptor in rat L6 myoblasts.
AB  - AIMS: Endothelin (ET) system plays a critical role in the development of insulin
      resistance and type 2 diabetes. In skeletal muscle, differentiation of myoblasts
      to myotubes is accompanied by the development of insulin sensitivity. Activation
      of extracellular signal-regulated kinase (ERK) 1/2 inhibits the differentiation
      of myoblasts, leading to insulin resistance. Although ET receptor (ETR)
      stimulation generally activates ERK1/2, the mechanism for ETR-mediated ERK1/2
      activation in skeletal muscle is unknown. The purpose of this study was to
      determine the signal transduction pathway involved in ET-1-stimulated ERK1/2
      phosphorylation in L6 myoblasts derived from rat skeletal muscle. MAIN METHODS:
      Changes in phosphorylation levels of ERK1/2 following stimulation with ET-1 were
      analyzed by Western blot in L6 myoblasts. To inhibit receptor internalization,
      dominant-negative dynamin (K44A) was overexpressed in L6 myoblasts using
      adenovirus-mediated gene transfer. KEY FINDINGS: ET-1 induced phosphorylation of
      ERK1/2 in L6 myoblasts. The ERK1/2 phosphorylation was abolished by BQ123 (a
      selective ET type A receptor (ETAR) antagonist), YM-254890 (a Galphaq/11 protein
      inhibitor), and AG370 (a platelet-derived growth factor receptor (PDGFR) kinase
      inhibitor), while U-73122 (a phospholipase C (PLC) inhibitor) was less potent.
      The ERK1/2 phosphorylation was inhibited by overexpression of dominant-negative
      dynamin (K44A). These results suggest that ETAR stimulation induces ERK1/2
      phosphorylation in L6 myoblasts through Gq/11 protein-dependent, PLC-independent
      PDGFR transactivation which requires dynamin-dependent ETAR internalization.
      SIGNIFICANCE: Because activation of ERK1/2 is considered to inhibit
      differentiation of myoblasts with the development of insulin sensitivity, the
      ETAR-mediated PDGFR transactivation and subsequent ERK1/2 activation play an
      important role in ET-1-induced insulin resistance.

PMID- 24735960
TI  - Assessment of circulatory and pulmonary endothelin-1 levels in a lavage-induced
      surfactant-depleted lung injury rabbit model with repeated open endotracheal
      suctioning and hyperinflation.
AB  - AIMS: Endothelin-1 (ET-1) is a mediator of various physiological and pathological
      processes, including vascular inflammation, cell proliferation and
      vasoconstriction. Attenuation of ET action using ET-1 antagonists reduces
      pulmonary vascular leakage and inflammation in several models of lung injuries
      and experimental acute respiratory distress syndrome (ARDS). Based on these
      earlier reports, the current study investigates the patterns of ET-1 levels in
      circulation and pulmonary tissues in an experimental model of lavage-induced
      surfactant-depleted lung injury. Additionally, we also test the effects of open
      endotracheal suctioning (OES) and hyperinflation (HI) as recruitment maneuver
      following OES on ET-1 levels. MAIN METHODS: Briefly, 24 Japanese white rabbits
      were anesthetized and intubated. Normal saline was instilled into the lung and
      washed mildly. After instillation, rabbits were ventilated at definite settings
      at a total duration of 3 hours. OES and HI were performed every 15 minutes from
      the beginning of the protocol. KEY FINDINGS: Here, we show that both circulatory
      and pulmonary ET-1 levels increased in models with lung injury induced by saline
      lavage compared to healthy control group. No further aggravation in expression of
      pulmonary ET-1 was seen after OES and HI, although OES and HI worsened arterial
      hypoxygenation and severity of lung injury. In contrast, circulatory ET-1 levels
      significantly decreased after OES and HI but were not associated with blood
      pressure changes. SIGNIFICANCE: We conclude that in a saline lavage-induced lung
      injury model, both circulatory and pulmonary ET-1 levels increased. Further, OES
      and HI exerted differential effects on ET-1 expression at both circulatory and
      pulmonary levels.

PMID- 24735961
TI  - Heterogeneous photocatalysis of moxifloxacin in water: chemical transformation
      and ecotoxicity.
AB  - This work provides new insights on the impact of TiO2/UV catalyzed chemical
      transformation of moxifloxacin on ecotoxicity effects towards the green alga
      Pseudokirchneriella subcapitata. The moxifloxacin median effect concentration (EC
      50=0.78 [0.56, 1.09] mg L(-1)), determined in accordance to the OECD 72-h growth
      inhibition test guideline, was 7 times lower than that of the older and widely
      used fluoroquinolone ciprofloxacin (EC-50=5.57 [4.86, 6.38] mg L(-1)). Applying
      heterogeneous photocatalysis as an advanced oxidation technique to degrade
      moxifloxacin in aqueous solution decreased the average growth inhibition from 72%
      to 14% after 150 min of treatment. No significant carbon mineralization was
      observed and liquid chromatography mass spectrometry analysis revealed the
      formation of 13 degradation products for which a chemical structure could be
      proposed based on accurate mass determination. Combined chemical and
      ecotoxicological analysis showed that as long as moxifloxacin is present in the
      reaction solution, it is the main compound affecting algal growth inhibition.
      However, also the contribution of the degradation products to the observed
      ecotoxicity cannot be neglected. Photocatalytically induced modifications of
      moxifloxacin mainly occur at the diazobicyclo-substituent as ring opening,
      oxidation into carbonyl groups, and hydroxylation. This results into the
      formation of more hydrophilic compounds with a decreased biological activity
      compared with moxifloxacin. The change in lipophilicity, and possibly a modified
      acid-base speciation, most probably also affect the cell membrane permeation of
      the degradation products, which might be another factor explaining the observed
      lower residual ecotoxicity of the photocatalytically treated reaction solutions.

PMID- 24735962
TI  - Frontline low-dose alemtuzumab with fludarabine and cyclophosphamide prolongs
      progression-free survival in high-risk CLL.
AB  - The randomized Haemato Oncology Foundation for Adults in The Netherlands 68 phase
      3 trial compared front-line chemotherapy with chemotherapy plus the CD52
      monoclonal antibody alemtuzumab for high-risk chronic lymphocytic leukemia,
      defined as at least 1 of the following: unmutated immunoglobulin heavy chain
      genes, deletion 17p or 11q, or trisomy 12. Fit patients were randomized to
      receive either 6 28-day cycles of oral FC chemotherapy (days 1 through 3:
      fludarabine 40 mg/m(2) per day and cyclophosphamide 250 mg/m(2) per day: n = 139)
      or FC plus subcutaneous alemtuzumab 30 mg day 1 (FCA, n = 133). FCA prolonged the
      primary end point, progression-free survival (3-year progression-free survival 53
      vs 37%, P = .01), but not the secondary end point, overall survival (OS).
      However, a post hoc analysis showed that FCA increased OS in patients younger
      than 65 years (3-year OS 85% vs 76%, P = .035). FCA also increased the overall
      response rate (88 vs 78%, P = .036), and the bone marrow minimal residual disease
      negative complete remission rate (64% vs 43%, P = .016). Opportunistic infections
      were more frequent following FCA, but without an increase in treatment related
      mortality (FCA: 3.8%, FC: 4.3%). FCA improves progression-free survival in high
      risk chronic lymphocytic leukemia. As anticipated, FCA is more immunosuppressive
      than FC, but with due vigilance, does not lead to a higher treatment-related
      mortality. This study was registered at www.trialregister.nl as trial no. NTR529.

PMID- 24735963
TI  - The role of HTLV-1 clonality, proviral structure, and genomic integration site in
      adult T-cell leukemia/lymphoma.
AB  - Adult T-cell leukemia/lymphoma (ATL) occurs in ~5% of human T-lymphotropic virus
      type 1 (HTLV-1)-infected individuals and is conventionally thought to be a
      monoclonal disease in which a single HTLV-1(+) T-cell clone progressively
      outcompetes others and undergoes malignant transformation. Here, using a
      sensitive high-throughput method, we quantified clonality in 197 ATL cases,
      identified genomic characteristics of the proviral integration sites in malignant
      and nonmalignant clones, and investigated the proviral features (genomic
      structure and 5' long terminal repeat methylation) that determine its capacity to
      express the HTLV-1 oncoprotein Tax. Of the dominant, presumed malignant clones,
      91% contained a single provirus. The genomic characteristics of the integration
      sites in the ATL clones resembled those of the frequent low-abundance clones
      (present in both ATL cases and carriers) and not those of the intermediate
      abundance clones observed in 24% of ATL cases, suggesting that oligoclonal
      proliferation per se does not cause malignant transformation. Gene ontology
      analysis revealed an association in 6% of cases between ATL and integration near
      host genes in 3 functional categories, including genes previously implicated in
      hematologic malignancies. In all cases of HTLV-1 infection, regardless of ATL,
      there was evidence of preferential survival of the provirus in vivo in
      acrocentric chromosomes (13, 14, 15, 21, and 22). 

PMID- 24735964
TI  - SDF-1 dynamically mediates megakaryocyte niche occupancy and thrombopoiesis at
      steady state and following radiation injury.
AB  - Megakaryocyte (MK) development in the bone marrow progresses spatially from the
      endosteal niche, which promotes MK progenitor proliferation, to the sinusoidal
      vascular niche, the site of terminal maturation and thrombopoiesis. The chemokine
      stromal cell-derived factor-1 (SDF-1), signaling through CXCR4, is implicated in
      the maturational chemotaxis of MKs toward sinusoidal vessels. Here, we
      demonstrate that both IV administration of SDF-1 and stabilization of endogenous
      SDF-1 acutely increase MK-vasculature association and thrombopoiesis with no
      change in MK number. In the setting of radiation injury, we find dynamic
      fluctuations in marrow SDF-1 distribution that spatially and temporally correlate
      with variations in MK niche occupancy. Stabilization of altered SDF-1 gradients
      directly affects MK location. Importantly, these SDF-1-mediated changes have
      functional consequences for platelet production, as the movement of MKs away from
      the vasculature decreases circulating platelets, while MK association with the
      vasculature increases circulating platelets. Finally, we demonstrate that
      manipulation of SDF-1 gradients can improve radiation-induced thrombocytopenia in
      a manner additive with earlier TPO treatment. Taken together, our data support
      the concept that SDF-1 regulates the spatial distribution of MKs in the marrow
      and consequently circulating platelet numbers. This knowledge of the
      microenvironmental regulation of the MK lineage could lead to improved
      therapeutic strategies for thrombocytopenia. 

PMID- 24735965
TI  - Lower risk for serious adverse events and no increased risk for cancer after PBSC
      vs BM donation.
AB  - We compared serious early and late events experienced by 2726 bone marrow (BM)
      and 6768 peripheral blood stem cell (PBSC) donors who underwent collection of
      PBSC or BM between 2004 and 2009 as part of a prospective study through the
      National Marrow Donor Program. Standardized FDA definitions for serious adverse
      events (SAEs) were used, and all events were reviewed by an independent physician
      panel. BM donors had an increased risk for SAEs (2.38% for BM vs 0.56% for PBSC;
      odds ratio [OR], 4.13; P < .001), and women were twice as likely to experience an
      SAE (OR for men, 0.50; P = .005). Restricting the analysis to life-threatening,
      unexpected, or chronic/disabling events, BM donors maintained an increased risk
      for SAEs (0.99% for BM vs 0.31% for PBSC; OR, 3.20; P < .001). Notably, the
      incidence of cancer, autoimmune illness, and thrombosis after donation was
      similar in BM vs PBSC donors. In addition, cancer incidence in PBSC donors was
      less than that reported in the general population (Surveillance, Epidemiology,
      and End Results Program database). In conclusion, SAEs after donation are rare
      but more often occurred in BM donors and women. In addition, there was no
      evidence of increased risk for cancer, autoimmune illness, and stroke in donors
      receiving granulocyte colony-stimulating factor during this period of
      observation. 

PMID- 24735966
TI  - Pearson marrow pancreas syndrome in patients suspected to have Diamond-Blackfan
      anemia.
AB  - Pearson marrow pancreas syndrome (PS) is a multisystem disorder caused by
      mitochondrial DNA (mtDNA) deletions. Diamond-Blackfan anemia (DBA) is a
      congenital hypoproliferative anemia in which mutations in ribosomal protein genes
      and GATA1 have been implicated. Both syndromes share several features including
      early onset of severe anemia, variable nonhematologic manifestations, sporadic
      genetic occurrence, and occasional spontaneous hematologic improvement. Because
      of the overlapping features and relative rarity of PS, we hypothesized that some
      patients in whom the leading clinical diagnosis is DBA actually have PS. Here, we
      evaluated patient DNA samples submitted for DBA genetic studies and found that 8
      (4.6%) of 173 genetically uncharacterized patients contained large mtDNA
      deletions. Only 2 (25%) of the patients had been diagnosed with PS on clinical
      grounds subsequent to sample submission. We conclude that PS can be overlooked,
      and that mtDNA deletion testing should be performed in the diagnostic evaluation
      of patients with congenital anemia. 

PMID- 24735969
TI  - Pre-operative overnight pulse oximetry to predict high dependency unit
      intervention in children undergoing adenotonsillectomy for obstructive sleep
      apnoea.
AB  - Background: Post-operative high dependency unit beds are often requested for
      patients undergoing adenotonsillectomy for obstructive sleep apnoea. This study
      evaluated the utilisation of high dependency unit beds for such cases at our
      institution, a paediatric tertiary referral centre. Method: A retrospective case
      note review of patients admitted to the high dependency unit following
      adenotonsillar surgery for obstructive sleep apnoea, over a two-year period, was
      performed. Results: Sixty-six cases were identified. Thirty-nine patients
      underwent pre-operative overnight pulse oximetry; of these, 30 patients had
      desaturations noted. Seventeen patients had significant post-operative
      desaturations. These were predicted in all 11 patients who had undergone pre
      operative pulse oximetry. The remaining six had not undergone pre-operative pulse
      oximetry. Nineteen patients required high dependency unit care; eight had
      experienced post-operative desaturations. Conclusion: High dependency unit care
      may be required following adenotonsillectomy for obstructive sleep apnoea. In
      this study, pre-operative overnight pulse oximetry had 100 per cent sensitivity
      in predicting post-operative desaturations, and may therefore aid the appropriate
      utilisation of high dependency unit beds for patients undergoing
      adenotonsillectomy for obstructive sleep apnoea.

PMID- 24735968
TI  - Depletion of Sf3b1 impairs proliferative capacity of hematopoietic stem cells but
      is not sufficient to induce myelodysplasia.
AB  - Numerous studies have recently reported mutations involving multiple components
      of the messenger RNA (mRNA) splicing machinery in patients with myelodysplastic
      syndrome (MDS). SF3B1 is mutated in 70% to 85% of refractory anemia with ringed
      sideroblasts (RARS) patients and is highly associated with the presence of RARS,
      although the pathological role of SF3B1 mutations in MDS-RARS has not been
      elucidated yet. Here, we analyzed the function of pre-mRNA splicing factor Sf3b1
      in hematopoiesis. Sf3b1(+/-) mice maintained almost normal hematopoiesis and did
      not develop hematological malignancies during a long observation period. However,
      Sf3b1(+/-) cells had a significantly impaired capacity to reconstitute
      hematopoiesis in a competitive setting and exhibited some enhancement of
      apoptosis, but they did not show any obvious defects in differentiation.
      Additional depletion of Sf3b1 with shRNA in Sf3b1(+/-) hematopoietic stem cells
      (HSCs) severely compromised their proliferative capacity both in vitro and in
      vivo. Finally, we unexpectedly found no changes in the frequencies of
      sideroblasts in either Sf3b1(+/-) erythroblasts or cultured Sf3b1(+/-)
      erythroblasts expressing shRNA against Sf3b1. Our findings indicate that the
      level of Sf3b1 expression is critical for the proliferative capacity of HSCs, but
      the haploinsufficiency for Sf3b1 is not sufficient to induce a RARS-like
      phenotype. 

PMID- 24735970
TI  - Differential neural control in early bilinguals and monolinguals during response
      inhibition.
AB  - We tested the hypothesis that early bilinguals and monolinguals use different
      brain areas when performing nonlinguistic executive control tasks. For this, we
      explored brain activity of early bilinguals and monolinguals during a manual stop
      signal paradigm. Behaviorally, bilinguals and monolinguals did not show
      significant differences in the task, which led us to compare brain activation
      that cannot be attributed to differences in performance. Analyses demonstrated
      that monolinguals activated the anterior cingulate cortex more than bilinguals
      when performing the stop-signal task. These results offer direct support for the
      notion that early bilingualism exerts an effect on neural circuitry responsible
      for executive control. Consistent with recent reports, we found that bilinguals
      used the anterior cingulate more efficiently than monolinguals to monitor
      nonlinguistic cognitive conflicts. 

PMID- 24735967
TI  - Premalignant PTEN-deficient thymocytes activate microRNAs miR-146a and miR-146b
      as a cellular defense against malignant transformation.
AB  - Cancer develops by a multistep process during which cells acquire characteristics
      that allow them to evade apoptosis and proliferate unchecked. Sequential
      acquisition of genetic alterations drives this process but also causes cellular
      stress, frequently prompting cells to enter a premalignant period during which
      they mount a defense against transformation. T cell-specific deletion of the
      tumor suppressor PTEN in mice induces premalignancy in the thymus and development
      of CD4(+) T-cell lymphomas in the periphery. Here we sought to identify factors
      mediating the cellular defense against transformation during the premalignant
      period. We identified several microRNAs upregulated specifically in premalignant
      thymocytes, including miR-146a, miR-146b, and the miR-183/96/182 cluster. CD4
      driven T cell-specific transgenic overexpression of mir-146a and mir-146b
      significantly delayed PTEN-deficient lymphomagenesis and delayed c-myc oncogene
      induction, a key driver of transformation in PTEN-deficient T-cell malignancies.
      We found that miR-146a and miR-146b targeting of Traf6 attenuates TCR signaling
      in the thymus and inhibits downstream NF-kappaB-dependent induction of c-myc.
      Additionally, c-myc repression in mature CD4 T cells by miR-146b impaired TCR
      mediated proliferation. Hence, we have identified 2 miRNAs that are upregulated
      as part of the cellular response against transformation that, when
      overrepresented, can effectively inhibit progression to malignancy in the context
      of PTEN deficiency.

PMID- 24735971
TI  - Temporal changes of the adrenal endocrine system in a restraint stressed mouse
      and possibility of postmortem indicators of prolonged psychological stress.
AB  - We investigated temporal changes of adrenal endocrine systems through the
      hypothalamic-pituitary-adrenal (HPA) and sympathetic-adrenomedullary (SA) axis in
      restraint stressed mice. Restraint stress for 1 day to 3 weeks caused a
      significant increase in serum levels of ACTH and glucocorticoids accompanied with
      an increase in adrenal weights, indicating activation of the HPA axis. Reflecting
      the overproduction of glucocorticoids, adrenal cholesterol content decreased.
      Moreover, adrenal gene expression involved in cholesterol supply, including
      scavenger receptor-class B type I, HMG-CoA reductase, and hormone-sensitive
      lipase, was increased over the same period. After 4 weeks stress, all of these
      changes returned to control levels. In contrast, adrenal gene expression of
      chromogranin A, which is cosecreted with catecholamine via the SA axis, was
      increased with 1 day to 2 weeks of stress, and decreased with 3-4 weeks of
      stress. Our results suggest that analyses of adrenal endocrine systems based on
      the combination of several markers examined here would be useful for not only
      proving prolonged psychological stress experience but also determining its
      duration.

PMID- 24735972
TI  - Novel homozygous inactivating mutation of the calcium-sensing receptor gene
      (CASR) in neonatal severe hyperparathyroidism-lack of effect of cinacalcet.
AB  - BACKGROUND: NSHPT is a life-threatening disorder caused by homozygous
      inactivating calcium-sensing receptor (CASR) mutations. In some cases, the CaSR
      allosteric activator, cinacalcet, may reduce serum PTH and calcium levels, but
      surgery is the treatment of choice. OBJECTIVE: To describe a case of NSHPT
      unresponsive to cinacalcet. PATIENT AND RESULTS: A 23-day-old girl was admitted
      with hypercalcemia, hypotonia, bell-shaped chest and respiratory distress. The
      parents were first-degree cousins once removed. Serum Ca was 4.75 mmol/l (N: 2.10
      2.62), P: 0.83 mmol/l (1.55-2.64), PTH: 1096 pg/ml (9-52) and urinary Ca/Cr
      ratio: 0.5mg/mg. First, calcitonin was given (10 IU/kg * 4/day), and then 2 days
      later, pamidronate (0.5mg/kg) for 2 days. Doses of cinacalcet were given daily
      from day 28 of life starting at 30 mg/m2 and increasing to 90 mg/m2 on day 43. On
      day 33, 6 days after pamidronate, serum Ca levels had fallen to 2.5 mmol/l but,
      thereafter, rose to 5 mmol/l despite the cinacalcet. Total parathyroidectomy was
      performed at day 45. Hungry bone disease after surgery required daily Ca
      replacement and calcitriol for 18 days. At 3 months, the girl was mildly
      hypercalcemic, with no supplementation, and at 6 months, she developed
      hypocalcemia and has since been maintained on Ca and calcitriol. By CASR mutation
      analysis, the infant was homozygous and both parents heterozygous for a deletion
      frameshift mutation. CONCLUSION: The predicted nonfunctional CaSR is consistent
      with lack of response to cinacalcet, but total parathyroidectomy was successful.
      An empiric trial of the drug and/or prompt mutation testing should help minimize
      the period of unnecessary pharmacotherapy.

PMID- 24735973
TI  - Associations between objectively-measured sedentary behaviour and physical
      activity with bone mineral density in adults and older adults, the NHANES study.
AB  - BACKGROUND: Lack of physical activity (PA) is an important modifiable risk factor
      for bone mineral density (BMD). Time spent in sedentary behaviour (SB), or time
      spent in non-exercising seated and reclining postures, has recently emerged as a
      new public health risk, independent of the amount of time someone spends being
      active. As national surveys report that adults spend on average 8h per day being
      sedentary, rising to 10h a day in older age, it has been hypothesised that a
      repeated exposure to sitting in modern daily life, whether it is for travelling,
      working or leisure, might have a deleterious effect on bone health in a way that
      mirrors the results of studies into the effect of lengthy periods of bed-rest.
      The aim of this study was to investigate for the first time a) how time spent in
      SB is associated with bone mineral density (BMD), b) whether this association
      changes depending on the amount of time spent engaging in different intensity
      levels of PA, and c) if the pattern of accumulation of SB and long uninterrupted
      periods of SB are associated with BMD. METHODS: The 2005/2006 National Health and
      Nutrition Examination Survey (NHANES), is a cross-sectional study of a
      representative sample of the US population that is conducted biannually by the
      National Centers for Disease Control. PA and SB were assessed objectively over 7
      days using an Actigraph accelerometer and BMD was measured via dual-energy X-ray
      absorptiometry. In this study, data are presented on four regions of the femur
      (femoral neck, trochanter, inter trochanter and total femur) and total spine (L1
      L4). The associations between BMD, SB and PA levels were examined using multiple
      linear regressions stratified by gender. In addition, the association between the
      pattern of accumulation of SB (quantified as frequency and duration of SB) and
      BMD was also investigated. All models were adjusted for known risk factors
      associated with BMD. In total, data for 2117 individuals, aged 23-90+years (males
      N=1158), were available to analyse SB and femur BMD and 1942 individuals (males
      N=1053) for analysis of SB and spine BMD. RESULTS: There was no evidence of an
      association between SB time and hip or spinal BMD in men. For men, time spent
      doing moderate to vigorous activity (MVPA) and vigorous activity (VIG) was
      associated with higher total femur and the other hip sub-region BMD. The
      regression coefficient was BMVPA=0.306 (95% CI: 0.021-0.591)g/cm2 for each 10
      minute increment in daily MVPA. For VIG, the regression coefficient is BVIG=0.320
      (95% CI: 0.058-0.583) but this cannot be interpreted linearly as time spent in
      vigorous activity was square root transformed. In women, SB was negatively
      associated with total femur BMD and all sub-regions but not MVPA nor VIG. The
      regression coefficient for total femur BMD was BSB = -0.159 (95% CI: -0.241
      0.076)g/cm2 for each 10 minute increment spent being sedentary each day. In
      addition, the duration of SB bouts was deleteriously associated with BMD for the
      total femur and of other hip sub-regions, but the number of bouts of SB did not
      have a significant effect. These associations were found to be independent of the
      amount of MVPA and VIG that women engage in. No associations were found between
      SB or PA and spinal BMD for either men or women. CONCLUSIONS: These results
      provide the first evidence that repeated exposure to sitting (SB), measured
      objectively in daily life, is deleteriously associated with BMD of the total
      femur and of all hip sub-regions in women, independent of the amount of time
      women engage in moderate and vigorous activity. This suggests that SB might be a
      risk factor for bone health in women independent of whether they engage in
      physical activity. In addition, the duration of SB bouts, rather than their
      frequency, appears to be deleteriously associated with BMD of the total femur and
      of all hip sub-regions. Future research should investigate the effect on bone
      health of interventions which set out to reduce SB and the duration of SB bouts
      in comparison, and as adjunct, to the promotion of PA. For men, SB is not
      significantly associated with BMD of the femur or spine and the results appear to
      confirm that moderate and vigorous activity has a protective effect.

PMID- 24735974
TI  - Analysis of strength and failure pattern of human proximal femur using
      quantitative computed tomography (QCT)-based finite element method.
AB  - This paper presents a novel method for fast and reliable prediction of the
      failure strength of human proximal femur, using the quantitative computed
      tomography (QCT)-based linear finite element analysis (FEA). Ten fresh frozen
      human femora (age: 34+/-16) were QCT-scanned and the pertinent 3D voxel-based
      finite element models were constructed. A specially-designed holding frame was
      used to define and maintain a unique geometrical reference system for both FEA
      and in-vitro mechanical testing. The analyses and tests were carried out at 8
      different loading orientations. A new scheme was developed for assortment of the
      element risk factor (defined as the ratio of the strain energy density to the
      yield strain energy for each element) and implemented for the prediction of the
      failure strength. The predicted and observed failure patterns were in
      correspondence, and the FEA predictions of the failure loads were in very good
      agreement with the experimental results (R2=0.86, slope=0.96, p<0.01). The
      average computational time was 5 min (on a regular desktop personal computer) for
      an average element number of 197,000. Noting that the run-time for a similar
      nonlinear model is about 8h, it was concluded that the proposed linear scheme is
      overwhelmingly efficient in terms of computational costs. Thus, it can
      efficiently be used to predict the femoral failure strength with the same
      accuracy of similar nonlinear models.

PMID- 24735975
TI  - Whole body vibration during fracture healing intensifies the effects of estradiol
      and raloxifene in estrogen-deficient rats.
AB  - Current osteoporosis therapies aim to delay bone destruction and have additional
      anabolic effects. While they have demonstrated some positive effects on bone
      healing, more progress is needed in this area. This study used the well-known
      osteoporotic agents estrogen (E) and raloxifene (R) in conjunction with
      biomechanical whole body vibration (WBV) at a frequency of 70 Hz twice daily for
      six weeks to stimulate bone healing. Eighty-four 3-month old female Sprague
      Dawley rats (12 per group) were bilaterally ovariectomized to develop osteopenia
      within eight weeks. Osteotomy of the metaphyseal tibiae was performed and
      fracture healing was then studied using mechanical tests, histomorphometry,
      computed tomography (MUCT), and gene analysis. We found that E and R improved the
      structure of osteopenic bones as did WBV alone, although significant levels for
      WBV were seldom reached. Combination treatments significantly enhanced stiffness
      (R+WBV; p<0.05), endosteal bone (R+WBV; p<0.01), and trabecular density (E+WBV;
      p<0.05, R+WBV; p<0.05). In addition, the expression of osteoclast-specific Trap
      was significantly reduced after treatment with E, R, or their combination with
      WBV (p<0.01). The effects were additive and not inhibitory, leading us to
      conclude that the combined applications of WBV with E or R may improve the
      healing of osteopenic bones. The therapies studied are all currently approved for
      human use, suggesting ready applicability to clinical practice. To better
      understand the effects of WBV on osteopenic bones, the ideal vibration regime
      will require further study.

PMID- 24735976
TI  - Diagnostic outcome management study in patients with clinically suspected
      recurrent acute pulmonary embolism with a structured algorithm.
AB  - INTRODUCTION: The value of diagnostic strategies in patients with clinically
      suspected recurrent pulmonary embolism (PE) has not been established. The aim was
      to determine the safety of a simple diagnostic strategy using the Wells clinical
      decision rule (CDR), quantitative D-dimer testing and computed tomography
      pulmonary angiography (CTPA) in patients with clinically suspected acute
      recurrent PE. MATERIALS AND METHODS: Multicenter clinical outcome study in 516
      consecutive patients with clinically suspected acute recurrent PE without using
      anticoagulants. RESULTS: An unlikely clinical probability (Wells rule 4 points or
      less) was found in 182 of 516 patients (35%), and the combination of an unlikely
      CDR-score and normal D-dimer result excluded PE in 88 of 516 patients (17%),
      without recurrent venous thromboembolism (VTE) during 3month follow-up (0%; 95%
      CI 0.0-3.4%). CTPA was performed in all other patients and confirmed recurrent PE
      in 172 patients (overall prevalence of PE 33%) and excluded PE in the remaining
      253 patients (49%). During follow-up, seven of these 253 patients returned with
      recurrent VTE (2.8%; 95% CI 1.2-5.5%), of which in one was fatal (0.4 %; 95 % CI
      0.02-1.9%). The diagnostic algorithm was feasible in 98% of patients.
      CONCLUSIONS: A diagnostic algorithm consisting of a clinical decision rule, D
      dimer test and CTPA is effective in the management of patients with clinically
      suspected acute recurrent PE. CTPA provides reasonable safety in excluding acute
      recurrent PE in patients with a likely clinical probability or an elevated D
      dimer test for recurrent PE, with a low risk for fatal PE at follow-up.

PMID- 24735977
TI  - Assessment of endothelial function by acetylcholine iontophoresis: impact of
      inter-electrode distance and electrical cutaneous resistance.
AB  - OBJECTIVES: Endothelial function can be assessed by acetylcholine (ACh)
      iontophoresis with single current application. The effect of inter-electrode
      distance as well as electrical cutaneous resistance (ECR) on ACh dependent
      vasodilation has never been studied using single current application. The aims of
      this study are (i) to compare ACh-peak and ECR measured at different inter
      electrode distances, (ii) to assess the relationship between ACh-peak and ECR,
      (iii) and to study the reproducibility of the ECR values. METHODS: Fourteen
      healthy subjects were included. Using laser speckle contrast imaging, ACh
      iontophoreses (0.1 mA, 30s) were performed on the forearm at a 7-day interval
      with an inter-electrode distance set at 5 cm. Two other inter-electrode distances
      were also evaluated: 10 cm and 15 cm. ECR was measured during each ACh
      iontophoresis as well as the ACh-peak. RESULTS: No statistical difference was
      found between the ACh-peak values obtained at 5 cm, 10 cm and 15 cm. ECRs were
      also not statistically different. An inverse relationship (r=-0.60) was found
      between the ACh-peak and ECR (p<0.05). The coefficient of variation of the inter
      day reproducibility of the ECR values was 9.1% [6.5%-15.1%] with an intra-class
      correlation coefficient of 0.93 [0.81-0.98]. CONCLUSION: Inter-electrode distance
      ranging from 5 cm to 15 cm changes neither the ACh-peak value nor the ECR value.
      ECR impacts ACh-peak values.

PMID- 24735978
TI  - CERKL interacts with mitochondrial TRX2 and protects retinal cells from oxidative
      stress-induced apoptosis.
AB  - Mutations in the ceramide kinase-like gene (CERKL) are associated with severe
      retinal degeneration. However, the exact function of the encoded protein (CERKL)
      remains unknown. Here we show that CERKL interacts with mitochondrial thioredoxin
      2 (TRX2) and maintains TRX2 in the reduced redox state. Overexpression of CERKL
      protects cells from apoptosis under oxidative stress, whereas suppressing CERKL
      renders cells more sensitive to oxidative stress. In zebrafish, CERKL protein
      prominently locates in the outer segment and inner segment of the photoreceptor
      of the retina. Knockdown of CERKL in the zebrafish leads to an increase of
      retinal cell death, including cone and rod photoreceptor degeneration. Signs of
      oxidative damage to macromolecules were also detected in CERKL deficient
      zebrafish retina. Our results show that CERKL interacts with TRX2 and plays a
      novel key role in the regulation of the TRX2 antioxidant pathway and, for the
      first time, provides an explanation of how mutations in CERKL may lead to retinal
      cell death. 

PMID- 24735979
TI  - TET2 gene expression and 5-hydroxymethylcytosine level in multiple sclerosis
      peripheral blood cells.
AB  - Aberrant DNA methylation can lead to genome destabilization and to deregulated
      gene expression. Recently, 5-hydroxymethylcytosine (5hmC), derived from oxidation
      of 5-methylcytosine (5mC) by the Ten-Eleven Translocation (TET) enzymes, has been
      detected. 5hmC is now considered as a new epigenetic DNA modification with
      relevant roles in cell homeostasis regulating DNA demethylation and
      transcription. Our aim was to investigate possible changes in the DNA
      methylation/demethylation machinery in MS. We assessed the expression of enzymes
      involved in DNA methylation/demethylation in peripheral blood mononuclear cells
      (PBMCs) from 40 subjects with MS and 40 matched healthy controls. We performed
      also, DNA methylation analysis of specific promoters and analysis of global
      levels of 5mC and 5hmC. We show that TET2 and DNMT1 expression is significantly
      down-regulated in MS PBMCs and it is associated with aberrant methylation of
      their promoters. Furthermore, 5hmC is decreased in MS PBMCs, probably as a result
      of the diminished TET2 level. 

PMID- 24735981
TI  - MFAP3L activation promotes colorectal cancer cell invasion and metastasis.
AB  - An abundance of microfibril-associated glycoprotein 3-like (MFAP3L) significantly
      correlates with distant metastasis in colorectal cancer (CRC), although the
      mechanism has yet to be explained. In this study, we observed that MFAP3L knock
      down resulted in reduced CRC cell invasion and hepatic metastasis. We evaluated
      the cellular location and biochemical functions of MFAP3L and found that this
      protein was primarily localized in the nucleus of CRC cells and acted as a
      protein kinase. When EGFR translocated into the nucleus upon stimulation with
      EGF, MFAP3L was phosphorylated at Tyr287 within its SH2 motif, and the activated
      form of MFAP3L phosphorylated ERK2 at Thr185 and Tyr187. Moreover, the metastatic
      behavior of CRC cells in vitro and in vivo could be partially explained by
      activation of the nuclear ERK pathway through MFAP3L phosphorylation. Hence, we
      experimentally demonstrated for the first time that MFAP3L likely participates in
      the nuclear signaling of EGFR and ERK2 and acts as a novel nuclear kinase that
      impacts CRC metastasis. 

PMID- 24735980
TI  - Neuropathological role of PI3K/Akt/mTOR axis in Down syndrome brain.
AB  - Down syndrome (DS) is the most frequent genetic cause of intellectual disability
      characterized by the presence of three copies of chromosome 21 (Chr21).
      Individuals with DS have sufficient neuropathology for a diagnosis of Alzheimer's
      disease (AD) after the age of 40years. The aim of our study is to gain new
      insights in the molecular mechanisms impaired in DS subjects that eventually lead
      to the development of dementia. We evaluate the PI3K/Akt/mTOR axis in the frontal
      cortex from DS cases (under the age of 40years) and DS with AD neuropathology
      compared with age-matched controls (Young and Old). The PI3K/Akt/mTOR axis may
      control several key pathways involved in AD that, if aberrantly regulated, affect
      amyloid beta (Abeta) deposition and tau phosphorylation. Our results show a
      hyperactivation of PI3K/Akt/mTOR axis in individuals with DS, with and without AD
      pathology, in comparison with respective controls. The PI3K/Akt/mTOR deregulation
      results in decreased autophagy, inhibition of IRS1 and GSK3beta activity.
      Moreover, our data suggest that aberrant activation of the PI3K/Akt/mTOR axis
      acts in parallel to RCAN1 in phosphorylating tau, in DS and DS/AD. In conclusion,
      this study provides insights into the neuropathological mechanisms that may be
      engaged during the development of AD in DS. We suggest that deregulation of this
      signaling cascade is already evident in young DS cases and persist in the
      presence of AD pathology. The impairment of the PI3K/Akt/mTOR axis in DS
      population might represent a key-contributing factor to the neurodegenerative
      process that culminates in Alzheimer-like dementia. 

PMID- 24735983
TI  - Hypofibrinogenemia caused by adrenocorticotropic hormone for infantile spasms: a
      case report.
AB  - We report the case of a 7-month-old boy who developed hypofibrinogenemia (66.6
      mg/dL; reference value, 170-405 mg/dL) during adrenocorticotropic hormone (ACTH)
      therapy for infantile spasms. Although the patient showed no clinical signs of a
      bleeding diathesis, we recommend that plasma fibrinogen levels should be
      monitored during ACTH therapy, which should be discontinued when fibrinogen
      levels fall below hemostatic levels (60.0mg/dL) or when bleeding tendencies are
      recognized.

PMID- 24735982
TI  - Safety and pharmacological characterization of the molecular tweezer CLR01 - a
      broad-spectrum inhibitor of amyloid proteins' toxicity.
AB  - BACKGROUND: The "molecular tweezer" CLR01 is a broad-spectrum inhibitor of
      abnormal protein self-assembly, which acts by binding selectively to Lys
      residues. CLR01 has been tested in several in vitro and in vivo models of
      amyloidoses all without signs of toxicity. With the goal of developing CLR01 as a
      therapeutic drug for Alzheimer's disease and other amyloidoses, here we studied
      its safety and pharmacokinetics. METHODS: Toxicity studies were performed in 2-m
      old wild-type mice. Toxicity was evaluated by serum chemical analysis,
      histopathology analysis, and qualitative behavioral analysis. Brain penetration
      studies were performed using radiolabeled CLR01 in both wild-type mice and a
      transgenic mouse model of Alzheimer's disease at 2-m, 12-m, and 22-m of age.
      Brain levels were measured from 0.5 - 72 h post administration. RESULTS:
      Examination of CLR01's effect on tubulin polymerization, representing normal
      protein assembly, showed disruption of the process only when 55-fold excess CLR01
      was used, supporting the compound's putative "process-specific" mechanism of
      action.A single-injection of 100 mg/kg CLR01 in mice - 2,500-fold higher than the
      efficacious dose reported previously, induced temporary distress and liver
      injury, but no mortality. Daily injection of doses up to 10 mg/kg did not produce
      any signs of toxicity, suggesting a high safety margin.The brain penetration of
      CLR01 was found to be 1 - 3% of blood levels depending on age. Though CLR01 was
      almost completely removed from the blood by 8 h, unexpectedly, brain levels of
      CLR01 remained steady over 72 h. CONCLUSION: Estimation of brain levels compared
      to amyloid beta-protein concentrations reported previously suggest that the
      stoichiometry obtained in vitro and in vivo is similar, supporting the mechanism
      of action of CLR01.The favorable safety margin of CLR01, together with efficacy
      shown in multiple animal models, support further development of CLR01 as a
      disease-modifying agent for amyloidoses.

PMID- 24735984
TI  - Executive functions in very-low-birth-weight young adults: a comparison between
      self-report and neuropsychological test results.
AB  - Executive functions are goal-directed control mechanisms that modulate the
      operation of other cognitive processes. Preterm born very-low-birth-weight (VLBW:
      birth weight<1500 grams) children have more problems with attention/executive
      function than their term born peers. The objective of this study is to examine if
      VLBW young adults had more self-reported attention/ executive problems and lower
      neuropsychological test results than controls. Furthermore, to investigate the
      relationship between self-reported attention/executive problems, general
      cognitive ability (IQ) and test results. Forty-two VLBW [mean birth weight 1237
      (219) grams, and gestational age 29.3 (2.4) weeks] and 63 term born controls at
      age 19 years completed The BRIEF-A self-report of attention/executive functions
      in everyday life. The Wechsler Adult Intelligence Scale III was used to obtain IQ
      scores; subtests from Delis-Kaplan were used to assess attention/executive
      function. There were no differences between the VLBW young adults and controls on
      any of the BRIEF-A measures, but the VLBW subjects had lower scores on 8 of the
      18 neuropsychological subtests (p<.01). Some correlations between BRIEF-A and the
      Stroop and TMT tests were found in the VLBW group. VLBW young adults do not
      report more problems regarding attention/executive function in daily life than
      controls despite lower results on several neuropsychological tests.

PMID- 24735985
TI  - The influence of study population and definition of improvement on the smallest
      detectable change and the minimal important change of the neck disability index.
AB  - BACKGROUND: Reported values of the minimal important change (MIC) and the
      smallest detectable change (SDC) for the neck disability index (NDI) differ
      strongly, raising questions about the generalizability of these parameters. The
      SDC and the MIC are possibly influenced by the study design or by the study
      population. We studied the influence of the type of anchor, the definition of
      improvement and population characteristics on the SDC and the MIC of the NDI.
      METHODS: A cohort study including 101 patients with non-specific, chronic neck
      pain. SDC and MIC were calculated using two types of external anchors. For each
      anchor we applied two different definitions to dichotomize the population into
      improved and unimproved patients. The influence of patient characteristics was
      assessed in relevant subgroups: patients with or without radiating pain and
      patients with different baseline scores. RESULTS: The influence of different
      anchors and different definitions of improvement on estimates of the SDC and the
      MIC was only minimal. The SDC and the MIC were similar for subgroups of patients
      with or without radiation, but differed strongly for subgroups of patients with
      higher or lower baseline scores. CONCLUSIONS: Our study shows that estimates of
      the SDC and the MIC of the NDI can be influenced by population characteristics.
      It is concluded that we cannot adopt a single change score to define relevant
      change by combining the result of previous studies.

PMID- 24735986
TI  - A computational simulation study on the acoustic pressure generated by a dental
      endosonic file: effects of intensity, file shape and volume.
AB  - One of the uses of ultrasound in dentistry is in the field of endodontics (i.e.
      root canal treatment) in order to enhance cleaning efficiency during the
      treatment. The acoustic pressures generated by the oscillation of files in narrow
      channels has been calculated using the COMSOL simulation package. Acoustic
      pressures in excess of the cavitation threshold can be generated and higher
      values were found in narrower channels. This parallels experimental observations
      of sonochemiluminescence. The effect of varying the channel width and length and
      the dimensions and shape of the file are reported. As well as explaining
      experimental observations, the work provides a basis for the further development
      and optimisation of the design of endosonic files. 

PMID- 24735987
TI  - [Validity and concordance of electronic health records in primary care (AP
      Madrid) for surveillance of diabetes mellitus. PREDIMERC study].
AB  - OBJECTIVE: To assess the validity and concordance of diabetes data in the
      electronic health records of primary care (Madrid-PC) by comparing with those
      from the PREDIMERC study. METHODS: The sensitivity, specificity, positive
      predictive value, negative predictive value and kappa index of diabetes cases
      recorded in the health records of Madrid-PC were calculated by using data from
      PREDIMERC as the gold standard. The prevalence of diabetes was also determined
      according to each data source. RESULTS: The sensitivity of diabetes recorded in
      Madrid-PC was 74%, the specificity was 98.8%, the positive predictive value was
      87.9%, the negative predictive value was 97.3%, and the kappa index was 0.78. The
      prevalence of diabetes recorded in Madrid-PC was 6.7% versus 8.1% by PREDIMERC,
      where known diabetes was 6.3%. CONCLUSIONS: The electronic health records of
      primary care are a valid source for epidemiological surveillance of diabetes in
      Madrid.

PMID- 24735988
TI  - Investigation of the role of major respiratory viruses in the aetiology of nasal
      polyps using polymerase chain reaction technique.
AB  - Objective: We aimed to identify the role of major respiratory viruses in the
      aetiology of human nasal polyps using polymerase chain reaction technique.
      Methods: Thirty patients with nasal polyps and a group of 20 healthy patients
      (control group) were included in this study. Mucosa was obtained from the polyps
      of patients with nasal polyposis and from the middle turbinate of the control
      group patients by means of biopsy. The samples were stored at -80  degrees C
      until molecular analysis by polymerase chain reaction was carried out. Results:
      In the control group, the human coronavirus and human rhinovirus were diagnosed
      in one of the patients and the human respiratory syncytial virus in another. In
      the group with nasal polyposis, the influenza B virus was identified in one of
      the patients and the human coronavirus in another. Conclusion: The results did
      not demonstrate a statistically significant relationship between nasal polyposis
      and respiratory viruses.

PMID- 24735989
TI  - Heavy metal bioaccumulation and mobility from rice plants to Nilaparvata lugens
      (Homoptera: Delphacidae) in China.
AB  - Samples of soils, rice plants, and the adult, long-winged, brown planthoppers,
      Nilaparvata lugens (Stal) (Homoptera: Delphacidae), were collected from 18 sites
      of 9 regions in southern China. The concentrations of seven elements (Cu, Zn, As,
      Mo, Ag, Cd, and Pb) were measured using inductively coupled plasma mass
      spectrometry. Heavy metal mobility and bioaccumulation were analyzed in the rice
      plant-N. lugens system. The concentrations of Zn, As, Cd, and Pb in rice plants
      were positively correlated with their relevant concentrations in soil samples The
      bioconcentration factors of the seven elements in the rice plant-N. lugens system
      showed that the order of metal accumulation was Mo>Zn>Ag>Cd>Cu>Pb>As. In
      particular, Mo and Zn showed significantly high accumulation in N. lugens. A
      cluster analysis and factor analysis showed that the bioaccumulation of these
      seven elements in the rice plant-N. lugens system could be classified into two
      groups, closely related to their molar mass. The first group consisted of five
      elements with relatively light molar masses: Cu, Zn, As, Mo, and Ag. Cu and Zn,
      which have nearly equal molar masses, showed similar accumulation levels in N.
      lugens. The second group included two elements with relatively heavy molar
      masses: Cd and Pb. This study demonstrated that bioaccumulation of seven heavy
      metals was regular in the rice plant-N. lugens system. N. lugens could be used as
      bioindicators of the contaminated degree for Zn in rice paddy fields. This
      information may provide a basis for future ecological research on the
      bioaccumulation mechanism in N. lugens. 

PMID- 24735990
TI  - The "Saatchi bill" will allow responsible innovation in treatment.

PMID- 24735991
TI  - Comparison of alkaline industrial wastes for aqueous mineral carbon sequestration
      through a parallel reactivity study.
AB  - Thirty-one alkaline industrial wastes from a wide range of industrial processes
      were acquired and screened for application in an aqueous carbon sequestration
      process. The wastes were evaluated for their potential to leach polyvalent
      cations and base species. Following mixing with a simple sodium bicarbonate
      solution, chemistries of the aqueous and solid phases were analyzed. Experimental
      results indicated that the most reactive materials were capable of sequestering
      between 77% and 93% of the available carbon under experimental conditions in four
      hours. These materials - cement kiln dust, spray dryer absorber ash, and
      circulating dry scrubber ash - are thus good candidates for detailed, process
      oriented studies. Chemical equilibrium modeling indicated that amorphous calcium
      carbonate is likely responsible for the observed sequestration. High variability
      and low reactive fractions render many other materials less attractive for
      further pursuit without considering preprocessing or activation techniques. 

PMID- 24735992
TI  - Mass, energy and material balances of SRF production process. Part 1: SRF
      produced from commercial and industrial waste.
AB  - This paper presents the mass, energy and material balances of a solid recovered
      fuel (SRF) production process. The SRF is produced from commercial and industrial
      waste (C&IW) through mechanical treatment (MT). In this work various streams of
      material produced in SRF production process are analyzed for their proximate and
      ultimate analysis. Based on this analysis and composition of process streams
      their mass, energy and material balances are established for SRF production
      process. Here mass balance describes the overall mass flow of input waste
      material in the various output streams, whereas material balance describes the
      mass flow of components of input waste stream (such as paper and cardboard, wood,
      plastic (soft), plastic (hard), textile and rubber) in the various output streams
      of SRF production process. A commercial scale experimental campaign was conducted
      on an MT waste sorting plant to produce SRF from C&IW. All the process streams
      (input and output) produced in this MT plant were sampled and treated according
      to the CEN standard methods for SRF: EN 15442 and EN 15443. The results from the
      mass balance of SRF production process showed that of the total input C&IW
      material to MT waste sorting plant, 62% was recovered in the form of SRF, 4% as
      ferrous metal, 1% as non-ferrous metal and 21% was sorted out as reject material,
      11.6% as fine fraction, and 0.4% as heavy fraction. The energy flow balance in
      various process streams of this SRF production process showed that of the total
      input energy content of C&IW to MT plant, 75% energy was recovered in the form of
      SRF, 20% belonged to the reject material stream and rest 5% belonged with the
      streams of fine fraction and heavy fraction. In the material balances, mass
      fractions of plastic (soft), plastic (hard), paper and cardboard and wood
      recovered in the SRF stream were 88%, 70%, 72% and 60% respectively of their
      input masses to MT plant. A high mass fraction of plastic (PVC), rubber material
      and non-combustibles (such as stone/rock and glass particles), was found in the
      reject material stream. 

PMID- 24735994
TI  - Second language phonology influences first language word naming.
AB  - The Masked Onset Priming Effect (MOPE) has been reported in speakers' first
      languages (L1). The aims of the present study are to investigate whether second
      language (L2) phonology is active during L1 reading, and to disentangle the
      contributions of orthography and phonology in reading aloud. To this end, Dutch
      English bilinguals read aloud L1 target words primed by L2 words, while
      electroencephalography (EEG) was recorded. The onset of the primes was
      manipulated to disentangle the contributions of orthography and phonology (i.e.
      O+P+: kite - KUNST, 'art'; O+P-: knee - KUNST; O-P+: crime - KUNST; O-P-: mine -
      KUNST). Phonological but not orthographic overlap facilitated RTs. However, event
      related brain potentials (ERPs) revealed both orthographic and phonological
      priming starting 125 ms after target presentation. Taken together, we gained
      insights into the time course of cross-linguistic priming and demonstrated that
      L2 phonology is activated rapidly in an L1 environment.

PMID- 24735993
TI  - Anatomy is strategy: skilled reading differences associated with structural
      connectivity differences in the reading network.
AB  - Are there multiple ways to be a skilled reader? To address this longstanding,
      unresolved question, we hypothesized that individual variability in using
      semantic information in reading aloud would be associated with neuroanatomical
      variation in pathways linking semantics and phonology. Left-hemisphere regions of
      interest for diffusion tensor imaging analysis were defined based on fMRI
      results, including two regions linked with semantic processing - angular gyrus
      (AG) and inferior temporal sulcus (ITS) - and two linked with phonological
      processing - posterior superior temporal gyrus (pSTG) and posterior middle
      temporal gyrus (pMTG). Effects of imageability (a semantic measure) on response
      times varied widely among individuals and covaried with the volume of pathways
      through the ITS and pMTG, and through AG and pSTG, partially overlapping the
      inferior longitudinal fasciculus and the posterior branch of the arcuate
      fasciculus. These results suggest strategy differences among skilled readers
      associated with structural variation in the neural reading network. 

PMID- 24735995
TI  - Changes in type II procollagen isoform expression during chondrogenesis by
      disruption of an alternative 5' splice site within Col2a1 exon 2.
AB  - This study describes a new mechanism controlling the production of alternatively
      spliced isoforms of type II procollagen (Col2a1) in vivo. During chondrogenesis,
      precursor chondrocytes predominantly produce isoforms containing alternatively
      spliced exon 2 (type IIA and IID) while Col2a1 mRNA devoid of exon 2 (type IIB)
      is the major isoform produced by differentiated chondrocytes. We previously
      identified an additional Col2a1 isoform containing a truncated exon 2 and
      premature termination codons in exon 6 (type IIC). This transcript is produced by
      utilization of another 5' splice site present in exon 2. To determine the role of
      this IIC splicing event in vivo, we generated transgenic mice containing silent
      knock-in mutations at the IIC 5' splice site (Col2a1-mIIC), thereby inhibiting
      production of IIC transcripts. Heterozygous and homozygous knock-in mice were
      viable and display no overt skeletal phenotype to date. However, RNA expression
      profiles revealed that chondrocytes in cartilage from an age range of Col2a1-mIIC
      mice produced higher levels of IIA and IID mRNAs and decreased levels of IIB
      mRNAs throughout pre-natal and post-natal development, when compared to
      chondrocytes from littermate control mice. Immunofluorescence analyses showed a
      clear increase in expression of embryonic type II collagen protein isoforms (i.e.
      containing the exon 2-encoded cysteine-rich (CR) protein domain) in cartilage
      extracellular matrix (ECM). Interestingly, at P14, P28 and P56, expression of
      embryonic Col2a1 isoforms in Col2a1-mIIC mice persisted in the pericellular
      domain of the ECM in articular and growth plate cartilage. We also show that
      persistent expression of the exon 2-encoded CR domain in the ECM of post-natal
      cartilage tissue may be due, in part, to the embryonic form of type XI collagen
      (the alpha3 chain of which is also encoded by the Col2a1 gene). In conclusion,
      expression of the Col2a1 IIC splice form may have a regulatory function in
      controlling alternative splicing of exon 2 to generate defined proportions of
      IIA, IID and IIB procollagen isoforms during cartilage development. Future
      studies will involve ultrastructural and biomechanical analysis of the collagen
      ECM to determine the effects of persistent mis-expression of embryonic collagen
      isoforms in mature cartilage tissue. 

PMID- 24735996
TI  - The effect of doxycycline treatment on the postvaccinal immune response in pigs.
AB  - The effect of a seven-day antibiotic therapy with doxycycline was investigated on
      the postvaccinal humoral and cellular immune response in pigs. The selected
      parameters of non-specific immunity were also studied. Fifty pigs were used
      (control not vaccinated (C, n=10), control vaccinated (CV, n=20), and
      experimental - received doxycycline (DOXY, n=20)). For vaccination live
      attenuated vaccine against pseudorabies (PR) was used. From day -1 to day 5 pigs
      from DOXY group received doxycycline orally with drinking water, at the
      recommended dose. Pigs from DOXY and CV groups were vaccinated at 8 and 10 weeks
      of age. The results of the present study showed that cell-mediated postvaccinal
      immune response can be modulated by oral treatment with doxycycline.
      Significantly lower values of stimulation index were observed after PRV
      restimulation in doxycycline-treated pigs. Moreover, in the DOXY group a
      significant decrease in IFN-gamma production after PRV restimulation was noted.
      The significantly lower number of CD4+CD8+ cells was also observed in doxy
      treated, vaccinated pigs, 2 weeks after final vaccination. Simultaneously,
      specific humoral response was not disturbed. This study demonstrated the
      importance of defining the immune modulatory activity of doxycycline because it
      may alter the immune responses to vaccines. The exact mechanism of T-cell
      response suppression by doxycycline remains to be elucidated, however the
      influence of doxycycline on the secretion of various cytokines, including IFN
      gamma, may be considered as a possible cause. The present observations should
      prompt further studies on the practical significance of such phenomena in terms
      of clinical implications.

PMID- 24735997
TI  - Comparison of anthropometric-based equations for estimation of body fat
      percentage in a normal-weight and overweight female cohort: validation via air
      displacement plethysmography.
AB  - OBJECTIVE: To evaluate the accuracy of the most commonly used anthropometric
      based equations in the estimation of percentage body fat (%BF) in both normal
      weight and overweight women using air-displacement plethysmography (ADP) as the
      criterion measure. DESIGN: A comparative study in which the equations of Durnin
      and Womersley (1974; DW) and Jackson, Pollock and Ward (1980) at three, four and
      seven sites (JPW3, JPW4 and JPW7) were validated against ADP in three groups.
      Group 1 included all participants, group 2 included participants with a BMI <25.0
      kg/m2 and group 3 included participants with a BMI >=25.0 kg/m2. SETTING: Human
      Performance Laboratory, Institute for Sport and Health, University College
      Dublin, Republic of Ireland. SUBJECTS: Forty-three female participants aged
      between 18 and 55 years. RESULTS: In all three groups, the %BF values estimated
      from the DW equation were closer to the criterion measure (i.e. ADP) than those
      estimated from the other equations. Of the three JPW equations, JPW3 provided the
      most accurate estimation of %BF when compared with ADP in all three groups.
      CONCLUSION: In comparison to ADP, these findings suggest that the DW equation is
      the most accurate anthropometric method for the estimation of %BF in both normal
      weight and overweight females.

PMID- 24735998
TI  - Developing an understanding of research-based nursing pedagogy among clinical
      instructors: a qualitative study.
AB  - BACKGROUND: Effective instruction is imperative to the learning process of
      clinical nursing instructors. Faculty members are required to provide high
      quality teaching and training by using new ways of teaching pedagogical methods
      to clinical instructors, which have transformed pedagogies from an exclusive
      clinical model to a holistic model. PURPOSE: The purpose of this study was to
      explore clinical instructors' use of planning, implementation, feedback loops,
      and reflection frameworks to apply research-based teaching and to examine the
      pedagogy used during field experience. METHOD: Data for the qualitative study
      were obtained from twenty purposefully sampled clinical teachers (n=20) via lists
      of questioned instructional practices and discussions, semi-structured
      interviews, observational notes, field notes, and written reflections. Data were
      analyzed by using a triangulation method to ensure trustworthiness, credibility,
      and reliability. FINDINGS: Three main themes emerged regarding the use of
      research-based teaching strategies: the need for learning about research-based
      pedagogy, support mechanisms to implement innovative teaching strategies, and
      transitioning from nursing student to nursing clinical instructors. CONCLUSION:
      It has been well documented that the nursing profession faces a serious shortage
      of nursing faculty, impacting the quality of clinical teaching. Developing
      clinical instructor programs to give students opportunities to select instructor
      pathways, focusing on knowledge promoting critical thinking and life-long
      professional development, is essential. Nursing colleges must collaborate by
      using a partnership model to achieve competency in planning, implementation,
      feedback loops, and reflection. Applying research-based clinical teaching
      requires the development of programs that integrate low-fidelity simulation and
      assisted instruction through the use of computers in Nursing Colleges.

PMID- 24735999
TI  - Degree of conversion and monomer elution of CQ/amine and TPO adhesives.
AB  - OBJECTIVE: To evaluate the effect of photo-initiator on the degree of conversion
      (DC) and elution of Bis-GMA and HEMA for 8 one-step adhesive formulations.
      METHODS: We used Scotchbond Universal ('SBU-CQ/amine_4.0', 3M ESPE), containing
      about 2wt% camphorquinone (CQ) and 2wt% ethyl-4-dimethylamino benzoate (EDMAB),
      an experimental 'SBU-TPO_2.1' version, containing 2.1wt% diphenyl(2,4,6
      trimethylbenzoyl)phosphine oxide (TPO), and 6 experimental LUB adhesives (Kuraray
      Noritake), namely 'LUB-CQ/amine_0.7', 'LUB-CQ/amine_1.4', 'LUB-CQ/amine_4.0',
      'LUB-TPO_0.35', 'LUB-TPO_0.7' and 'LUB-TPO_2.0', respectively containing 0.35wt%
      CQ and 0.35wt% EDMAB, 0.7wt% CQ and 0.7wt% EDMAB, 2.0wt% CQ and 2.0wt% EDMAB,
      0.35wt% TPO, 0.7wt% TPO, and 2.0wt% TPO. DC was measured using micro-Raman
      spectroscopy. Additional specimens were immersed in ethanol for 24h to determine
      the elution of Bis-GMA and HEMA using HPLC. RESULTS: DC of the respective SBU and
      LUB adhesives was alike at high photo-initiator concentration. At low
      concentration, TPO was significantly more efficient than CQ/amine (LUB adhesives
      only). A statistically significant positive photo-initiator concentration effect
      on DC was noted for both CQ/amine and TPO (LUB adhesives only). A statistically
      significant inverse photo-initiator concentration effect on HEMA elution was
      noted for both the CQ/amine- and TPO-containing LUB adhesives. A significantly
      strong correlation was found between DC and Bis-GMA elution (R(2)=0.744,
      p=0.026), and between DC and HEMA elution (R(2)=0.913, p=0.002) for the LUB
      adhesives. SIGNIFICANCE: The photo-initiator kind and concentration affect DC and
      the Bis-GMA/HEMA elution. TPO can be used as an alternative photo-initiator for
      CQ/amine.

PMID- 24736000
TI  - Effectiveness of a novel immunogenic nanoparticle platform for Toxoplasma peptide
      vaccine in HLA transgenic mice.
AB  - We created and produced a novel self-assembling nanoparticle platform for
      delivery of peptide epitopes that induces CD8(+) and CD4(+)T cells that are
      protective against Toxoplasma gondii infection. These self-assembling polypeptide
      nanoparticles (SAPNs) are composed of linear peptide (LP) monomers which contain
      two coiled-coil oligomerization domains, the dense granule 7 (GRA720-28
      LPQFATAAT) peptide and a universal CD4(+)T cell epitope (derived from PADRE).
      Purified LPs assemble into nanoparticles with icosahedral symmetry, similar to
      the capsids of small viruses. These particles were evaluated for their efficacy
      in eliciting IFN-gamma by splenocytes of HLA-B*0702 transgenic mice and for their
      ability to protect against subsequent T. gondii challenge. This work demonstrates
      the feasibility of using this platform approach with a CD8(+) epitope that binds
      HLA-B7 and tests the biological activity of potentially protective peptides
      restricted by human major histocompatibility complex (HLA) class I molecules in
      HLA transgenic mice. 

PMID- 24736001
TI  - Assurance of neuroattenuation of a live vaccine against West Nile virus: a
      comprehensive study of neuropathogenesis after infection with chimeric
      WN/DEN4Delta30 vaccine in comparison to two parental viruses and a surrogate
      flavivirus reference vaccine.
AB  - The upsurge of West Nile virus (WNV) human infections in 2012 suggests that the
      US can expect periodic WNV outbreaks in the future. Availability of safe and
      effective vaccines against WNV in endemic areas, particularly for aging
      populations that are at high risk of West Nile neuroinvasive disease (WNND),
      could be beneficial. WN/DEN4Delta30 is a live, attenuated chimeric vaccine
      against WNV produced by replacement of the genes encoding the pre-membrane and
      envelope protein genes of the vaccine virus against dengue virus type 4
      (DEN4Delta30) with corresponding sequences derived from a wild type WNV.
      Following intrathalamic inoculation of nonhuman primates (NHPs), a comprehensive
      neuropathogenesis study was performed and neurovirulence of WN/DEN4Delta30
      vaccine candidate was compared to that of two parental viruses (i.e., WNV and
      DEN4Delta30), as well as to that of an attenuated flavivirus surrogate reference
      (i.e., yellow fever YF 17D). Clinical and virological data, as well as results of
      a semi-quantitative histopathological analysis, demonstrated that WN/DEN4Delta30
      vaccine is highly attenuated for the central nervous system (CNS) of NHPs in
      comparison to a wild type WNV. Importantly, based on the virus replicative
      ability in the CNS of NHPs and the degree of induced histopathological changes,
      the level of neuroattenuation of WN/DEN4Delta30 vaccine was similar to that of YF
      17D, and therefore within an acceptable range. In addition, we show that the
      DEN4Delta30 vaccine tested in this study also has a low neurovirulence profile.
      In summary, our results demonstrate a high level of neuroattenuation of two
      vaccine candidates, WN/DEN4Delta30 and DEN4Delta30. We also show here a
      remarkable sensitivity of our WNV-NY99 NHP model, as well as striking resemblance
      of the observed neuropathology to that seen in human WNND. These results support
      the use of this NHP model for translational studies of WNV neuropathogenesis
      and/or testing the effectiveness of vaccines and therapeutic approaches. 

PMID- 24736002
TI  - Impact of rotavirus vaccination on diarrhea-related hospitalizations in Sao Paulo
      State, Brazil.
AB  - INTRODUCTION: Following introduction of routine infant rotavirus vaccination,
      severe diarrhea hospitalization rates declined among children aged <5 years
      throughout Brazil. Ensuring equity of rotavirus vaccine impact is important in
      countries that self-finance immunization programs. The objective of this study
      was to examine rotavirus vaccine impact on diarrhea admission rates among
      children aged <5 years in Brazil's public health system, according to area-based
      measures of human development in the state of Sao Paulo, Brazil. METHODS:
      Ecological analysis of public health system hospitalization rates for acute
      gastroenteritis among children aged <5 years in the state of Sao Paulo, Brazil,
      according to five categories of municipal development based on a modified Human
      Development Index for municipalities. Acute gastroenteritis hospitalization rates
      among children aged <5 years after national rotavirus vaccine introduction (2008
      2011) were compared to rates in pre-vaccine years (2000-2005) to calculate
      percent decline in rates (1-rate ratio) and 95% confidence intervals (CI) for
      each municipal development category. Direct hospitalization costs during the two
      periods were compared. RESULTS: Annual rates declined by 40% (95% CI, 39-42%)
      from 631 diarrhea hospitalizations per 100,000 person years pre-rotavirus
      vaccination to 377 per 100,000 post-vaccination among children aged <5 years and
      50% (95% CI, 48-52%) from 1009 to 505 per 100,000 among infants. Highest rates
      were observed in least developed municipalities. Significant declines of 26-52%
      among children <5 years and 41-63% among infants were observed in all categories
      of municipal development. Lower diarrhea hospitalization rates resulted in annual
      savings of approximately 2 million USD for the state of Sao Paulo. Savings in
      direct hospitalization costs benefitted municipalities in all five categories.
      CONCLUSION: The introduction of rotavirus vaccination was associated with
      substantial reductions of diarrhea-related admissions at all levels of municipal
      development in Sao Paulo State, Brazil.

PMID- 24736003
TI  - Footrot vaccines and vaccination.
AB  - Research on footrot in small ruminants, which is caused by Dichelobacter nodosus,
      has led to development of vaccines and their application for control, treatment
      and eradication of the disease in sheep. Footrot vaccines have evolved over
      decades to contain monovalent whole cell, multivalent recombinant fimbrial, and
      finally mono or bivalent recombinant fimbrial antigens. Initially whole cell
      vaccines made against the few known serogroups of D. nodosus were found to be
      inefficient in control of the disease in the field, which was attributed to the
      presence of other unidentified serogroups and also the use of inefficient
      adjuvants. Fimbriae or pili, which are the basis for antigenic variation, were
      found to be the major protective and also curative antigens but they are not
      cross protective between the different serogroups. Multivalent vaccines
      incorporating all the known serogroups have been proven to be of limited efficacy
      due to the phenomenon of antigenic competition. Recent studies in Nepal, Bhutan
      and Australia have shown that outbreak-specific vaccination which involves
      targeting identified serogroups with mono- or bivalent recombinant fimbrial
      vaccines, can be very effective in sheep and goats. Where multiple serogroups are
      present in a flock, antigenic competition can be overcome by sequentially
      targeting the serogroups with different bivalent vaccines every 3 months. A
      common antigen which would confer immunity to all serogroups would be the ideal
      immunogen but the initial studies were not successful in this area. Until
      universal antigen/s are available, flock specific mono or bivalent fimbrial
      vaccines are likely to be the most effective tool for control and eradication of
      footrot in sheep and goats. Future research in footrot vaccines should be focused
      on improving the duration of prophylaxis by incorporating new and emerging
      immunomodulators or adjuvants with modified delivery vehicles, discovering a
      common antigen and understanding the mechanisms of acquired immunity. 

PMID- 24736005
TI  - Predictors of optional immunization uptake in an urban south Indian population.
AB  - BACKGROUND: In Tamil Nadu, India, bacille Calmette-Guerin, diphtheria-tetanus
      pertussis, oral poliomyelitis, hepatitis B, and measles vaccines are part of the
      routine immunization schedule and are available free from government health
      centers. All other vaccines are optional and available in the private sector at a
      cost to families. This study assesses immunization rates of routine and optional
      vaccines and examines parental attitudes toward vaccines in Pallavapuram, Tamil
      Nadu. METHODS: The cluster sampling method was used to estimate immunization
      coverage. Seven children 18 to 36 months old were selected from 30 clusters for a
      total sample of 210 children. Demographics and vaccination data were collected
      from interviews and immunization records. Predictors of vaccination status were
      identified with logistic regression models. In addition, 21 parents participated
      in semi-structured interviews regarding their attitudes toward vaccination.
      Interviews were analyzed qualitatively for themes. RESULTS: Eighty one percent of
      children were fully immunized with routine vaccines. However, only 21% received
      all "major" optional vaccines, defined as 3 doses of Haemophilus influenzae type
      b vaccine, one dose of measles, mumps, rubella vaccine, and one dose of varicella
      zoster virus vaccine. Birth in a private hospital (OR 5.6, 95% CI 1.3 to 22.9,
      P<0.01), higher income (P=0.03), and maternal completion of high school (OR 6.4,
      95% CI 1.5 to 27.6, P<0.01) were significant predictors of receiving all major
      optional vaccines. Elucidated themes from interviews included (1) strong parental
      support for immunizations, (2) low concern for side effects, and (3) low uptake
      of optional vaccines due to high cost and lack of awareness. CONCLUSIONS:
      Coverage of optional vaccines is low despite positive attitudes toward
      immunizations. Efforts to reduce cost and increase awareness of these vaccines
      particularly among low-income families or to include these vaccines in the
      routine schedule may increase uptake and reduce morbidity and mortality from
      vaccine-preventable diseases.

PMID- 24736004
TI  - Breast milk and Group B streptococcal infection: vector of transmission or
      vehicle for protection?
AB  - Invasive Group-B streptococcal (GBS) disease is a leading cause of infant
      mortality and morbidity worldwide. GBS colonises the maternal rectum and vagina
      and transmission of bacteria from a colonized mother to her infant at birth is an
      important risk factor for GBS disease. GBS disease has also been associated with
      case reports of transmission via infected breast milk raising questions about
      mode of acquisition and transmission of this enteric pathogen and the development
      of neonatal disease. However, most breastfed infants remain unaffected by GBS in
      breast milk. Mechanisms associated with transmission of GBS in breast milk and
      potential factors that may protect the infant from transmission remain poorly
      understood. Understanding factors involved in protection or transmission of GBS
      infection via breast milk is important both for premature infants who are a high
      risk group and for infants in the developing world where breastfeeding is the
      only sustainable infant feeding option. In this review we discuss the proposed
      mechanisms for GBS colonization in breast milk on one hand and its immune factors
      that may protect from transmission of GBS from mother to infant on the other.
      Innate and adaptive immune factors, including serotype-specific antibody and
      their significance in the prevention of infant disease are presented. We further
      report on the role of human oligosaccharides in protection from invasive GBS
      disease. Advances in our knowledge about breast milk and immunity in GBS disease
      are needed to fully appreciate what might mitigate transmission from mother to
      infant and protect neonates from this devastating disease and to contribute to
      the development of novel prevention strategies, including maternal immunization
      to prevent infant disease. 

PMID- 24736007
TI  - Metastatic retropharyngeal lymph nodes: comparison of CT and MR imaging for
      diagnostic accuracy.
AB  - PURPOSE: The purpose of this study was to compare the diagnostic accuracies of CT
      and MR imaging for the detection of metastatic retropharyngeal lymph nodes (RLNs)
      in patients with nasopharyngeal and oropharyngeal squamous cell carcinoma (SCC).
      MATERIALS AND METHODS: The study included 38 patients (28 men and 10 women; mean
      age, 65 years; age range, 48-82 years) with nasopharyngeal (n=15) and
      oropharyngeal (n=23) SCC who underwent both contrast-enhanced CT and MR imaging
      before chemoradiotherapy. RLNs were classified as malignant or benign on the
      basis of the results of follow-up MR imaging. Two radiologists independently
      evaluated the images for diagnosing metastatic RLNs. RESULTS: Among a total of 68
      RLNs (minimum diameter, >= 4 mm) that were detected on gadolinium-enhanced fat
      suppressed T1-weighted images, 30 (44%) were malignant and 38 (56%) were benign.
      The sensitivities of CT versus MRI were 60% versus 97% for observer 1 (p<0.01)
      and 37% versus 90% for observer 2 (p<0.01). The specificities of CT versus MRI
      were 92% versus 97% for observer 1 (p=0.50) and 92% versus 100% for observer 2
      (p=0.25). The areas under the receiver operating characteristic curve (AUC) for
      CT versus MRI were 0.788 versus 0.996 for observer 1 (p<0.01) and 0.693 versus
      0.961 for observer 2 (p<0.01). CONCLUSION: MR imaging was superior to CT for the
      detection of metastatic RLNs.

PMID- 24736006
TI  - Purified coronavirus spike protein nanoparticles induce coronavirus neutralizing
      antibodies in mice.
AB  - Development of vaccination strategies for emerging pathogens are particularly
      challenging because of the sudden nature of their emergence and the long process
      needed for traditional vaccine development. Therefore, there is a need for
      development of a rapid method of vaccine development that can respond to emerging
      pathogens in a short time frame. The emergence of severe acute respiratory
      syndrome coronavirus (SARS-CoV) in 2003 and Middle East Respiratory Syndrome
      Coronavirus (MERS-CoV) in late 2012 demonstrate the importance of coronaviruses
      as emerging pathogens. The spike glycoproteins of coronaviruses reside on the
      surface of the virion and are responsible for virus entry. The spike glycoprotein
      is the major immunodominant antigen of coronaviruses and has proven to be an
      excellent target for vaccine designs that seek to block coronavirus entry and
      promote antibody targeting of infected cells. Vaccination strategies for
      coronaviruses have involved live attenuated virus, recombinant viruses, non
      replicative virus-like particles expressing coronavirus proteins or DNA plasmids
      expressing coronavirus genes. None of these strategies has progressed to an
      approved human coronavirus vaccine in the ten years since SARS-CoV emerged. Here
      we describe a novel method for generating MERS-CoV and SARS-CoV full-length spike
      nanoparticles, which in combination with adjuvants are able to produce high titer
      antibodies in mice. 

PMID- 24736009
TI  - Patient and public involvement: in theory and in practice.
AB  - Background: You've probably heard of patient and public involvement by now. You
      may even have 'involved' people in your research. But why involve patients,
      carers and members of the public at all? Is it just another hoop to jump through
      when preparing a research funding application for submission, or could it
      actually add something to your research? Could involving patients and members of
      the public even help you to design and deliver better research, with outcomes
      focused directly on the needs of your patient group? Objective: This article aims
      to answer some of these questions. It considers the theory underpinning patient
      and public involvement. This is followed by practical suggestions and advice to
      help you develop (or further develop if you already involve people!) patient and
      public involvement within your own research. There is also a case study to
      illustrate some of the main points, and extracts written by members of Research
      Design Service North East Consumer Panels.

PMID- 24736008
TI  - Ultrasound and computed tomography features of primary acinic cell carcinoma in
      the parotid gland: a retrospective study.
AB  - OBJECTIVE: The aim of this study was to characterize the ultrasound (US) and
      computed tomography (CT) findings of primary acinic cell carcinoma (AciCC) of the
      parotid gland. SUBJECTS AND METHODS: Seventy patients (70 lesions) with
      histopathologically proven AciCC underwent US or CT examination. The following
      characteristics were assessed on US images: size, shape, border, echogenicity,
      echotexture, internal structure, distal acoustic enhancement, and vascularity.
      The following characteristics were evaluated on CT images: size, shape, border,
      density, CT values on plain and contrast-enhanced scans, enhancement pattern,
      enhancement degree, and surrounding bone destruction. RESULTS: On US images,
      lesions were irregular, well-defined, hypoechoic, heterogeneous, and poorly
      vascularized. On CT images, lesions were regular and well-defined, and showed
      slight heterogeneous enhancement. CONCLUSION: These findings suggest that most
      primary AciCCs show benign features on US and CT.

PMID- 24736010
TI  - Is the rate of postoperative complications following laparoscopy-assisted
      gastrectomy higher in elderly patients than in younger patients?
AB  - BACKGROUND: With an increase in life expectancy, very elderly patients are
      presenting with gastric cancer more commonly than ever. The present study
      retrospectively analyzed the surgical outcomes of laparoscopy-assisted
      gastrectomy for gastric cancer in the young, elderly, and very elderly age
      groups. METHODS: The study group consisted of 1,055 patients who underwent
      laparoscopy-assisted gastrectomy between February 2002 and December 2012. We
      divided these patients into three groups; group 1 (young age, <65 years), group 2
      (elderly age, 65-74 years), and group 3 (very elderly age, >=75 years). RESULTS:
      There were statistical differences in the rates of postoperative complications
      among the three groups (P = 0.008). However, when assessed according to the
      severity of postoperative complications based on the Clavien-Dindo
      classification, there was no statistical difference among the three groups (P =
      0.562). CONCLUSIONS: Laparoscopy-assisted gastrectomy for gastric cancer can be
      performed in very elderly patients. In analyzing studies of elderly patients with
      postoperative complications following the procedure, not only should the rate of
      postoperative complications be taken into consideration, but also the severity of
      any postoperative complications.

PMID- 24736011
TI  - Hereditary spherocytosis complicated with lower limb ulcers in a pregnant
      patient.

PMID- 24736012
TI  - Detection of donor-specific antibodies in kidney transplantation.
AB  - INTRODUCTION: Precise and timely detection of human leukocyte antigen (HLA) donor
      specific antibodies (DSAs) is vital for evaluating humoral immune status of
      patients pre- and post-transplantation. SOURCE OF DATA: Clinically relevant
      articles on theory, development, methodology and application of HLA-DSA testing
      in kidney transplantation. AREAS OF AGREEMENT AND CONTROVERSY: The availability
      of solid phase HLA-antibody testing revolutionized our ability to detect HLA-DSA
      and to appreciate their significance in kidney transplant outcome. The best
      approach to determine the strength, immunogenicity and pathogenicity of HLA
      antibodies still remains controversial. GROWING POINTS: Assays to identify
      complement-binding antibodies were developed. Their clinical utilization, pre-
      and post-transplantation, is currently under investigation. Appreciation of the
      complexity of HLA-DQ antibodies should lead to better assignment of unacceptable
      antibodies and cPRA calculation. AREAS TIMELY FOR DEVELOPING RESEARCH:
      Characterization of HLA-antibody epitopes, and utilization of epitope matching to
      better define compatible donors could contribute to better transplant outcomes.

PMID- 24736013
TI  - The role of eccentric exercise in sport injuries rehabilitation.
AB  - INTRODUCTION: Sports injuries frequently involve tendons, muscles and ligaments.
      The variable outcome of surgery and medical treatment support early functional
      treatments. Eccentric exercise (EE) showed effectiveness in the management of
      Achilles tendinopathy (AT), patellar tendinopathy (PT) and lateral epicondyle
      tendinopathy (LET). Preliminary results of EE in other tendinopathies and sports
      injuries suggest its wide prescription in the sport rehabilitation field. SOURCES
      OF DATA: A comprehensive search of PubMed, Web of Science, the Cochrane
      Collaboration Database, Physiotherapy Evidence Database (PEDro), Evidence Based
      Medicine (EBM) Search review, National Guidelines, Scopus and Google Scholar was
      performed using keywords such as 'eccentric exercise', 'sports injuries
      rehabilitation', 'tendinopathy', 'hamstrings strain' 'adductor injuries' and 'ACL
      reconstruction rehabilitation'. AREAS OF AGREEMENT: EE, alone or associated with
      other therapies, represents a feasible, cost-effective and successful tool in the
      treatment of well-known targets and might be promising in shoulder tendinopathy,
      adductor-related groin pain, hamstring strains, and ACL rehabilitation. AREA OF
      CONTROVERSY: The lack of standardization of protocols, the variable amount,
      quality and follow-up of studies, the different anatomy and pathophysiology of
      the therapeutic targets limit the evidence of applicability of EE to sports
      injuries. GROWING POINTS: The role of pathology and biomechanics in the response
      to EE should be further investigated. AREAS TIMELY FOR DEVELOPING RESEARCH: New
      randomized controlled trials should test the effectiveness of standardized EE
      regimens to various sites of sports injuries.

PMID- 24736014
TI  - Ceramic-on-ceramic total hip arthroplasty: is squeaking related to an inaccurate
      three-dimensional hip anatomy reconstruction?
AB  - Many factors were incriminated in the squeaking generation in ceramic-on-ceramic
      total hip arthroplasty (THA), including the cup positioning and design. However,
      the influence of the stem orientation has not been investigated and the true
      three-dimensional hip anatomy has never been compared to the contralateral
      healthy hip. Three patients, who underwent unilateral ceramic-on-ceramic THA,
      complained of squeaking. CT-scans were performed to compare the true three
      dimensional hip anatomy to the contralateral healthy hip. All patients presented
      evidence of posterior neck-rim impingement with a two-fold increase in the global
      anteversion (above 75 degrees ) comparatively to the healthy hip. The excess of
      anteversion was on the cup side in 2 cases and on the stem side in 1 case. We
      conclude that squeaking in ceramic-on-ceramic THA could be related to a poor
      accuracy of 3D hip anatomy reconstruction which generated a posterior impingement
      and subsequent anterior edge loading because of excessive global anteversion. 

PMID- 24736015
TI  - External fixation of the thalamic portion of a fractured calcaneus: a new
      surgical technique.
AB  - The optimal treatment for intra-articular calcaneus fractures remains
      controversial, despite internal fixation techniques providing good results. The
      major point of contention is the need to reconstruct the overall morphology
      versus to restore the anatomy of the subtalar joint perfectly. We will describe a
      two-stage technique for treating intra-articular calcaneus fractures in which the
      primary fracture line goes through the thalamic fragment. The first procedure
      focuses on the overall morphology by restoring the height and length with
      osteotaxis being accomplished with a medial external fixator. The second
      procedure consists of internal fixation through a minimally invasive lateral
      approach to restore the anatomy of the articular facets. Any defects are filled
      with injectable bone substitute. This novel technique is compared to the
      complication rates and radiology and anatomy outcomes in published studies. This
      two-stage surgical technique reduces the length of hospital stays and the number
      of complications. 

PMID- 24736016
TI  - Treatment and outcome of open dislocation of the ankle with complete talar
      extrusion: a case report.
AB  - BACKGROUND: Open total talar extrusion is a severe, disabling ankle injuries. The
      most appropriate treatment (reimplantation versus talar body removal and
      tibiocalcaneal arthrodesis) is still a controversial challenge; outcomes and
      fearful potential complications are not predictable. OBJECTIVE: To report the
      case of an open ankle dislocation with talar extrusion, focusing on treatment
      modality and outcomes. METHOD: Immediate reduction, surgical debridement and
      external fixation were performed under antibiotic coverage. Wound closure was
      achieved with accurate debridement, postoperative strict clinical surveillance
      and meticulous handling of medications. The patient maintained external fixator
      for three weeks, then kept non-weight bearing with a cast for an additional four
      weeks. RESULTS: The patient's wound healed with no complications. Full weight
      bearing was gained at 12 weeks postoperation. At 18 months postoperatively, the
      patient did not develop any infection or a vascular necrosis, which are the major
      complications associated to talar extrusion. CONCLUSIONS: Good treatment
      procedure for a such severe open trauma, based on accurate debridement, wound
      care and stable temporary immobilization with external fixation allow reduction
      of infection risk and made preservation of extruded talus a successful option to
      preserve function and normal hindfoot anatomy at first instance. Talectomy should
      be considered as a salvage procedure.

PMID- 24736017
TI  - Exploring the bacterial microbiota associated with native South American species
      of Aphis (Hemiptera: Aphididae).
AB  - Aphids harbor a variety of bacterial endosymbionts, including the obligate
      symbiont Buchnera aphidicola and diverse facultative symbionts. The former
      supplies its host with essential amino acids. The latter are not indispensable
      for insect survival, but often improve their host's fitness. To date, the study
      of such associations was restricted to aphids of Holarctic origin. The bacterial
      microbiota of seven Aphis species from Argentina was investigated. The presence
      of B. aphidicola was assessed by specific PCR. Additional symbionts were
      identified through PCR with eubacterial universal primers, cloning, and
      sequencing of nearly complete 16S rRNA gene, intergenic spacer region, and
      partial 23S rRNA gene and subjected to phylogenetic analysis. Infection with B.
      aphidicola was confirmed in every species analyzed. The facultative symbiont
      Serratia symbiotica was detected in Aphis malalhuina Mier Durante, Nieto Nafria &
      Ortego, 2003, Aphis senecionicoides Blanchard, 1944, and Aphis schinifoliae
      Blanchard, 1939, while Hamiltonella defensa was identified in Aphis mendocina
      Mier Durante, Ortego & Nieto Nafria, 2006. Arsenophonus sp. was found infecting
      Aphis melosae Mier Durante & Ortego, 1999, and a new, undescribed Aphis sp. In
      Aphis danielae Remaudiere, 1994, no facultative symbionts could be recorded. When
      analyzing the highly conserved 16S rRNA gene, the phylogenetic tree grouped the
      S. symbiotica, H. defensa, and Arsenophonus isolates into three well-defined
      clusters showing little variability among clones corresponding to the same aphid
      host species. This article reports for the first time the endosymbionts
      associated with aphids native to South America. Despite their geographic origin,
      the qualitative composition of their microbiota revealed no evident differences
      from that described for aphids in the Northern Hemisphere. 

PMID- 24736018
TI  - Prophylactic vertebroplasty can decrease the fracture risk of adjacent vertebrae:
      an in vitro cadaveric study.
AB  - Adjacent level vertebral fractures are common in patients with osteoporotic wedge
      fractures, but can theoretically be prevented with prophylactic vertebroplasty.
      Previous tests on prophylactic vertebroplasties have been performed under axial
      loading, while in vivo changes in spinal alignment likely cause off-axis loads.
      In this study we determined whether prophylactic vertebroplasty can also reduce
      the fracture risk under off-axis loads. In a previous study, we tested vertebral
      bodies that were loaded axially or 20 degrees  off-axis representing vertebrae in
      an unfractured spine or vertebrae adjacent to a wedge fracture, respectively. In
      the current study, vertebral failure load and stiffness of our previously tested
      vertebral bodies were compared to those of a new group of vertebral bodies that
      were filled with bone cement and then loaded 20 degrees  off-axis. These
      vertebral bodies represented adjacent-level vertebrae with prophylactic bone
      cement filling. Prophylactic augmentation resulted in failure loads that were
      comparable to those of the 0 degrees  group, and 32% greater than the failure
      loads of the 20 degrees  group. The stiffness of the prophylacticly augmented
      vertebrae was 21% lower than that of the 0 degrees  group, but 27% higher than
      that of the 20 degrees  group. We conclude that prophylactic augmentation can
      decrease the fracture risk in a malaligned, osteoporotic vertebra. Whether this
      is enough to actually prevent additional vertebral fractures in vivo remains
      subject of further study. 

PMID- 24736019
TI  - The effect of different humeral prosthesis fin designs on shoulder stability: a
      computational model.
AB  - Humeral prostheses commonly use a fin structure as an attachment point for the
      supraspinatus muscle in total shoulder arthroplasty (TSA), but these fins may
      cause injury to the muscle during implantation, inadvertently influencing
      stability. In order to prevent supraspinatus injury, the effect of different
      humeral prostheses on shoulder joint stability needs to be investigated. A
      commercially available prosthesis and two modified humeral prostheses that
      substituted the fin structure for 2 (2H) or 3 holes (3H) were evaluated using
      computational models. Glenohumeral abduction was simulated and the
      superioinferior/anterioposterior stability of the shoulder joint after TSA was
      calculated. The results revealed that the 2H design had better superioinferior
      stability than the other prostheses, but was still less stable than the intact
      shoulder. There were no obvious differences in anterioposterior stability, but
      the motion patterns were clearly distinguishable from the intact shoulder model.
      In conclusion, the 2H design showed better superioinferior stability than the 3H
      design and the commercial product during glenohumeral joint abduction; the three
      prostheses show similar results in anterioposterior stability. However, the
      stability of each tested prosthesis was not comparable to the intact shoulder.
      Therefore, as a compromise, the 2H design should be considered for TSA because of
      its superior stability. 

PMID- 24736020
TI  - Analysis of the effects of surface stiffness on the contact interaction between a
      finger and a cylindrical handle using a three-dimensional hybrid model.
AB  - Contact interactions between the hand and handle, such as the contact surface
      softness and contact surface curvature, will affect both physical effort and
      musculoskeletal fatigue, thereby the comfort and safety of power tool operations.
      Previous models of hand gripping can be categorized into two groups: multi-body
      dynamic models and finite element (FE) models. The goal of the current study is
      to develop a hybrid FE hand gripping model, which combines the features of
      conventional FE models and multi-body dynamic models. The proposed model is
      applied to simulate hand-gripping on a cylindrical handle with covering materials
      of different softness levels. The model included three finger segments (distal,
      middle, and proximal phalanxes), three finger joints (the distal interphalangeal
      (DIP), proximal interphalangeal (PIP), and metacarpophalangeal (MCP) joint), and
      major anatomical substructures. The model was driven by joint moments, which are
      the net effects of all passive and active muscular forces acting about the
      joints. The finger model was first calibrated by using experimental data of human
      subject tests, and then applied to investigate the effects of surface softness on
      contact interactions between a finger and a cylindrical handle. Our results show
      that the maximal compressive stress and strain in the soft tissues of the fingers
      can be effectively reduced by reducing the stiffness of the covering material. 

PMID- 24736021
TI  - TAT conjugated cationic noble metal nanoparticles for gene delivery to epidermal
      stem cells.
AB  - Most nonviral gene delivery systems are not efficient enough to manipulate the
      difficult-to-transfect cell types, including non-dividing, primary, neuronal or
      stem cells, due to a lack of an intrinsic capacity to enter the membrane and
      nucleus, release its DNA payload, and activate transcription. Noble metal
      nanoclusters have emerged as a fascinating area of widespread interest in
      nanomaterials. Herein, we report the synthesis of the TAT peptide conjugated
      cationic noble metal nanoparticles (metal NPs@PEI-TAT) as highly efficient
      carriers for gene delivery to stem cells. The metal NPs@PEI-TAT integrate the
      advantages of metal NPs and peptides: the presence of metal NPs can effectively
      decrease the cytotoxicity of cationic molecules, making it possible to apply them
      in biological systems, while the cell penetrating peptides are essential for
      enhanced cellular and nucleus entry to achieve high transfection efficiency. Our
      studies provide strong evidence that the metal NPs@PEI-TAT can be engineered as
      gene delivery agents for stem cells and subsequently enhance their directed
      differentiation for biomedical application. 

PMID- 24736022
TI  - The feasibility and safety of same-day discharge after robotic-assisted
      hysterectomy alone or with other procedures for benign and malignant indications.
AB  - OBJECTIVE: This study aimed to report the feasibility and safety of same-day
      discharge after robotic-assisted hysterectomy. METHODS: Same-day discharge after
      robotic-assisted hysterectomy was initiated 07/2010. All cases from then through
      12/2012 were captured for quality assessment monitoring. The distance from the
      hospital to patients' homes was determined using http://maps.google.com.
      Procedures were categorized as simple (TLH+/-BSO) or complex (TLH+/-BSO with
      sentinel node mapping, pelvic and/or aortic nodal dissection, appendectomy, or
      omentectomy). Urgent care center (UCC) visits and readmissions within 30days of
      surgery were captured, and time to the visit was determined from the initial
      surgical date. RESULTS: Same-day discharge was planned in 200 cases. Median age
      was 52years (range, 30-78), BMI was 26.8kg/m(2) (range, 17.4-56.8), and ASA was
      class 2 (range, 1-3). Median distance traveled was 31.5miles (range, 0.2-149).
      Procedures were simple in 109 (55%) and complex in 91 (45%) cases. The indication
      for surgery was: endometrial cancer (n=82; 41%), ovarian cancer (n=5; 2.5%),
      cervical cancer (n=8; 4%), and non-gynecologic cancer/benign (n=105; 53%). One
      hundred fifty-seven (78%) had successful same-day discharge. Median time for
      discharge for these cases was 4.8h (range, 2.4-10.3). Operative time, case ending
      before 6pm, and use of intraoperative ketorolac were associated with successful
      same-day discharge. UCC visits occurred in 8/157 (5.1%) same-day discharge cases
      compared to 5/43 (11.6%) requiring admission (P=.08). Readmission was necessary
      in 4/157 (2.5%) same-day discharge cases compared to 3/43 (7.0%) requiring
      admission (P=.02). CONCLUSIONS: Same-day discharge after robotic-assisted
      hysterectomy for benign and malignant conditions is feasible and safe.

PMID- 24736023
TI  - Inhibition of Wnt/beta-catenin pathway by niclosamide: a therapeutic target for
      ovarian cancer.
AB  - Objective. The Wnt/beta-catenin pathway is known to regulate cellular
      proliferation and plays a role in chemoresistance. Niclosamide, an FDA approved
      salicyclamide derivative used for the treatment of tapeworm infections, targets
      the Wnt/beta-catenin pathway. Therefore, the objective of this study was to
      investigate niclosamide as a potential therapeutic agent for ovarian cancer.
      Methods. Tumor cells isolated from 34 patients' ascites with primary ovarian
      cancer were treated with niclosamide (0.1 to 5 MUM) +/- carboplatin (5 to 150
      MUM). Cell viability was assessed using the ATP-lite assay. LRP6, Axin 2, Cyclin
      D1, survivin and cytosolic free beta-catenin levels were determined using Western
      blot analysis. Tumorspheres were treated, and Wnt transcriptional activity was
      measured by the TOPflash reporter assay. ALDH and CD133 were analyzed by Flow
      cytometry and IHC. ALDH1A1 and LRP6 were analyzed by IHC in solid tumor and in
      ascites before and after treatment with niclosamide. Results. Combination
      treatment produced increased cytotoxicity compared to single agent treatment in
      32/34 patient samples. Western blot analysis showed a decrease in Wnt/beta
      catenin pathway proteins and the expression of target genes. A significant
      reduction of Wnt/beta-catenin signaling was confirmed by TOPflash assay. There
      was increased staining of ALDH1A1 and LRP6 in ascites compared to solid tumor
      which decreased after treatment. Conclusion. This study demonstrates that
      niclosamide is a potent Wnt/beta-catenin inhibitor. Targeting the Wnt/beta
      catenin pathway led to decreased cellular proliferation and increased cell death.
      These findings warrant further research of this drug and other niclosamide
      analogs as a treatment option for ovarian cancer.

PMID- 24736024
TI  - Effect of statin on risk of gynecologic cancers: a meta-analysis of observational
      studies and randomized controlled trials.
AB  - Objective. Epidemiologic and clinical findings are inconsistent concerning the
      risk for gynecologic cancers associated with statin use. We conducted a detailed
      meta-analysis of all relevant original studies to evaluate the effects of statin
      on the risk of gynecologic cancers. Methods. We searched PubMed, Embase, and
      Cochrane library databases up to February 2014 looking for eligible studies.
      Summary relative risk (RR) estimates and 95% confidence intervals (CIs) were used
      to calculate the risk using random-effects models. Results. A total of 14 (4
      randomized controlled trials, 5 cohorts, and 5 case-control) studies, involving
      12,904 gynecologic cancer cases, contributed to the analysis. Pooled results
      indicated a non-significant decrease of total gynecologic cancer risk among
      statin users (RR=0.89; 95% CI, 0.78-1.01). Stratified analyses across cancer site
      revealed a modest protective effect of statin on ovarian cancer (RR=0.79; 95% CI,
      0.64-0.98), while no association was found for endometrial cancer (RR=0.90; 95%
      CI, 0.75-1.07). The effect of statin use against cervical cancer and vulvar
      cancer is not conclusive. Furthermore, long-term statin use (>5years use) did not
      significantly affect the risk of endometrial cancer (RR=0.69; 95% CI, 0.44-1.10),
      but had an obvious decrease on the risk of ovarian cancer (RR=0.48; 95% CI, 0.28
      0.80). Conclusions. Our results suggest that statin use was inversely associated
      with ovarian cancer risk, and the association was stronger for long-term statin
      use (>5years). The evidence for a protective effect of statin use against other
      gynecologic cancers is suggestive but not conclusive, which deserves further
      investigation. 

PMID- 24736025
TI  - Effect of methyl jasmonate on cadmium uptake and antioxidative capacity in
      Kandelia obovata seedlings under cadmium stress.
AB  - This study investigated the effects of methyl jasmonate (MeJA) on chlorophyll
      concentration, lipid peroxidation, Cd uptake, antioxidative capacity, and type-2
      metallothionein gene (KoMT2) expression in the leaves of Kandelia obovata
      seedlings exposed to Cd stress. Deleterious effects, including decreased
      chlorophyll content and increased malondialdehyde concentration, were observed in
      leaves of K. obovata after 9d of 200MUmol L(-1) Cd treatment. Application of MeJA
      (0.1 to 1MUmol L(-1)) increased the concentration of ascorbic acid and the
      activities of catalase and ascorbate peroxidase in the leaves of K. obovata,
      which helped alleviate the oxidative damage induced by Cd stress. The
      concentration of endogenous jasmonic acid in the leaves of K. obovata was
      decreased by Cd but was positively stimulated by exogenous MeJA. The expression
      of KoMT2 in the leaves was enhanced after 9d of 200MUmol L(-1) Cd treatment,
      while the exogenous application of MeJA significantly restored the expression of
      KoMT2. Exogenous MeJA also inhibited the uptake of Cd to the aboveground part
      (leaves) of the seedlings, which helped reduce direct damages of Cd to the
      photosynthetic organ of the plant. The reduced uptake of Cd might be a result of
      stomatal closure and decreased transpiration by exogenous MeJA.

PMID- 24736026
TI  - Benzene homologues in environmental matrixes from a pesticide chemical region in
      China: Occurrence, health risk and management.
AB  - The contamination status and health risks of benzene, toluene, ethylbenzene and
      xylene (BTEX) in air, soil, dust and groundwater were evaluated in a pesticide
      chemical region located in Hebei province, China. The concentrations of BTEX in
      air ranged from 7.80 to 238ug/m(3) and those in soil and dust ranged from lower
      than limit of detection (LOD) to 32,360ng/g dw, and those in groundwater varied
      from 2.68 to 98.6ug/L. Generally, the levels of BTEX in multimedia matrixes were
      all below the standards established in China. Health risk assessment was
      performed based on the monitoring data via inhalation, dermal contact and
      ingestion pathways and hazard quotient (HQ) was calculated to be on the order of
      10(-7), below 10(-6), and Hazard index (HI) levels of BTEX were lower than 1.0.
      However, both HQ and HI ascended with an increase in work experience/exposure.
      Integrated risk management was proposed to eliminate BTEX pollution and to
      protect occupational health of workers in those industries. 

PMID- 24736027
TI  - Partitioning of paralytic shellfish toxins in sub-cellular fractions of the
      digestive gland of the cockle Cerastoderma edule: Changes under post-bloom
      natural conditions.
AB  - Concentrations of paralytic shellfish toxins (C1+2, B1, dcGTX2+3, dcSTX, GTX2+3
      and STX) were determined by LC-FLD in composite samples of digestive glands of
      the cockle Cerastoderma edule and in each sub-cellular particulate fractions
      obtained after differential centrifugation (nuclei+debris, mitochondria,
      lysosomes and microsomes). The specimens were sampled during the exposure to a
      bloom of Gymnodinium catenatum (day 0) and in the subsequent 8, 12, 14, 19, 21
      and 25 days under natural depuration conditions. Toxin profiles of digestive
      glands were dominated by C1+2 followed by B1 and dcGTX2+3, although the
      proportion between C1+2 and B1 contents decreased with the time, indicating a
      slower elimination of B1. All toxins, except GTX2+3 and STX, were quantified in
      the four sub-cellular fractions. The content of the quantified toxins decreased
      most markedly in nuclei+debris and microsomal fractions, during the first eight
      and 12 days, respectively. Conversely, different patterns were observed among
      toxins in mitochondrial and lysosomal fractions. The less accentuated decreases
      of dcGTX2+3 and dcSTX contents in the mitochondrial fraction may have resulted
      from the conversion of other toxins, like C1+2 and B1, associated with enzymatic
      activities in that fraction. The largest discrepancy was registered in lysosomal
      fraction for B1, since its content increased after eight days of post-bloom
      conditions. Input of B1 may come from the conversion of other toxins, like the
      abundant B2 and C1+2. These transformations are associated to the major role of
      lysosomes in the intra-cellular digestive process of materials acquired through
      vesicular transport. 

PMID- 24736028
TI  - Estrogens are neuroprotective factors for hypertensive encephalopathy.
AB  - Estrogens are neuroprotective factors for brain diseases, including hypertensive
      encephalopathy. In particular, the hippocampus is highly damaged by high blood
      pressure, with several hippocampus functions being altered in humans and animal
      models of hypertension. Working with a genetic model of primary hypertension, the
      spontaneously hypertensive rat (SHR), we have shown that SHR present decreased
      dentate gyrus neurogenesis, astrogliosis, low expression of brain derived
      neurotrophic factor (BDNF), decreased number of neurons in the hilus of the
      dentate gyrus, increased basal levels of the estrogen-synthesizing enzyme
      aromatase, and atrophic dendritic arbor with low spine density in the CA1 region
      compared to normotensive Wistar Kyoto (WKY) ratsl. Changes also occur in the
      hypothalamus of SHR, with increased expression of the hypertensinogenic peptide
      arginine vasopressin (AVP) and its V1b receptor. Following chronic estradiol
      treatment, SHR show decreased blood pressure, enhanced hippocampus neurogenesis,
      decreased the reactive astrogliosis, increased BDNF mRNA and protein expression
      in the dentate gyrus, increased neuronal number in the hilus of the dentate
      gyrus, further increased the hyperexpression of aromatase and replaced spine
      number with remodeling of the dendritic arbor of the CA1 region. We have detected
      by qPCR the estradiol receptors ERalpha and ERbeta in hippocampus from both SHR
      and WKY rats, suggesting direct effects of estradiol on brain cells. We
      hypothesize that a combination of exogenously given estrogens plus those locally
      synthesized by estradiol-stimulated aromatase may better alleviate the
      hippocampal and hypothalamic encephalopathy of SHR. This article is part of a
      Special Issue entitled "Sex steroids and brain disorders". 

PMID- 24736029
TI  - Development of a patient safety climate survey for Chinese hospitals: cross
      national adaptation and psychometric evaluation.
AB  - BACKGROUND: Existing patient safety climate instruments, most of which have been
      developed in the USA, may not accurately reflect the conditions in the healthcare
      systems of other countries. OBJECTIVES: To develop and evaluate a patient safety
      climate instrument for healthcare workers in Chinese hospitals. METHODS: Based on
      a review of existing instruments, expert panel review, focus groups and cognitive
      interviews, we developed items relevant to patient safety climate in Chinese
      hospitals. The draft instrument was distributed to 1700 hospital workers from 54
      units in six hospitals in five Chinese cities between July and October 2011, and
      1464 completed surveys were received. We performed exploratory and confirmatory
      factor analyses and estimated internal consistency reliability, within-unit
      agreement, between-unit variation, unit-mean reliability, correlation between
      multi-item composites, and association between the composites and two single
      items of perceived safety. RESULTS: The final instrument included 34 items
      organised into nine composites: institutional commitment to safety, unit
      management support for safety, organisational learning, safety system, adequacy
      of safety arrangements, error reporting, communication and peer support, teamwork
      and staffing. All composites had acceptable unit-mean reliabilities (>=0.74) and
      within-unit agreement (Rwg >=0.71), and exhibited significant between-unit
      variation with intraclass correlation coefficients ranging from 9% to 21%.
      Internal consistency reliabilities ranged from 0.59 to 0.88 and were >=0.70 for
      eight of the nine composites. Correlations between composites ranged from 0.27 to
      0.73. All composites were positively and significantly associated with the two
      perceived safety items. CONCLUSIONS: The Chinese Hospital Survey on Patient
      Safety Climate demonstrates adequate dimensionality, reliability and validity.
      The integration of qualitative and quantitative methods is essential to produce
      an instrument that is culturally appropriate for Chinese hospitals.

PMID- 24736030
TI  - In the spotlight: healthcare inspections as an opportunity for trainee clinicians
      to be the leaders of today.
AB  - There have been repeated calls from all quarters of healthcare for more
      clinicians to be leaders. The risks of not accepting this responsibility have
      been demonstrated by harrowing reports into failed care in England. Ambiguity
      persists over what clinical leadership encompasses, how it can be developed and
      how to inspire clinicians to practise it. A supportive organisational culture,
      dedicated resources and national support are needed to foster leadership skills
      among trainee clinicians. Here we discuss a possible blueprint based on the
      recent reviews of English NHS Trusts with high mortality rates for future
      initiatives in empowering medical and nursing trainees to learn from leaders and
      practise leadership skills. 

PMID- 24736031
TI  - Physiology of Geobacter metallireducens under excess and limitation of electron
      donors. Part II. Mimicking environmental conditions during cultivation in
      retentostats.
AB  - The strict anaerobe Geobacter metallireducens was cultivated in retentostats
      under acetate and acetate plus benzoate limitation in the presence of Fe(III)
      citrate in order to investigate its physiology under close to natural conditions.
      Growth rates below 0.003h(-1) were achieved in the course of cultivation. A nano
      liquid chromatography-tandem mass spectrometry-based proteomic approach (nano-LC
      MS/MS) with subsequent label-free quantification was performed on proteins
      extracted from cells sampled at different time points during retentostat
      cultivation. Proteins detected at low (0.002h(-1)) and high (0.06h(-1)) growth
      rates were compared between corresponding growth conditions (acetate or acetate
      plus benzoate). Carbon limitation significantly increased the abundances of
      several catabolic proteins involved in the degradation of substrates not present
      in the medium (ethanol, butyrate, fatty acids, and aromatic compounds). Growth
      rate-specific physiology was reflected in the changed abundances of energy-,
      chemotaxis-, oxidative stress-, and transport-related proteins. Mimicking natural
      conditions by extremely slow bacterial growth allowed to show how G.
      metallireducens optimized its physiology in order to survive in its natural
      habitats, since it was prepared to consume several carbon sources simultaneously
      and to withstand various environmental stresses. 

PMID- 24736032
TI  - Ultrasonography-diagnosed non-alcoholic fatty liver disease is not associated
      with prevalent ischemic heart disease among diabetics in a multiracial Asian
      hospital clinic population.
AB  - BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) and cardiovascular diseases
      are both common among patients with diabetes mellitus. OBJECTIVE: The aim of this
      study is to determine if ultrasonography-diagnosed NAFLD is associated with
      prevalent ischemic heart disease (IHD) among patients with diabetes mellitus.
      METHODS: This is a cross-sectional study on consecutive patients seen at the
      Diabetic Clinic, University of Malaya Medical Centre. The medical record for each
      patient was reviewed for documented IHD. Patients without documented IHD but had
      symptoms and/or electrocardiographic changes suggestive of IHD were referred for
      cardiac evaluation. RESULTS: Data for 399 patients were analyzed. Mean age was
      62.8+/-10.5 years with 43.1% male. NAFLD and IHD were present in 49.6 and 26.6%,
      respectively. The prevalence of IHD among patients with and without NAFLD was
      24.7 and 28.4%, respectively (P=0.414). The prevalence of IHD was highest among
      the Indians (34.1%) followed by the Malays (29.2%) and the Chinese (20.1%). No
      association was found between NAFLD and IHD when analyzed according to ethnicity.
      On multivariate analysis, independent factors associated with IHD were older age,
      lower levels of physical activity, greater waist circumference and higher serum
      glycated hemoglobin level. CONCLUSIONS: Ultrasonography-diagnosed NAFLD was not
      associated with prevalent IHD among patients with diabetes mellitus in a
      multiracial Asian hospital clinic population.

PMID- 24736033
TI  - A practical approach to the child with abnormal liver tests.
AB  - The presence of elevated aminotransferases on routine blood tests can reveal
      liver diseases of various severities. In children, etiologies are more numerous
      and complex than those usually considered in adults. Information derived from
      family and personal history, physical examination and basic laboratory data are
      necessary to reach a timely and correct diagnosis. A stepwise approach is
      proposed to guide the timing of more specific investigations that are often
      required. 

PMID- 24736034
TI  - Severe acute neurological symptoms related to proton pump inhibitors induced
      hypomagnesemia responsible for profound hypoparathyroidism with hypocalcemia.

PMID- 24736035
TI  - Introducing structured caregiver training in stroke care: findings from the TRACS
      process evaluation study.
AB  - OBJECTIVE: To evaluate the process of implementation of the modified London
      Stroke Carers Training Course (LSCTC) in the Training Caregivers After Stroke
      (TRACS) cluster randomised trial and contribute to the interpretation of the
      TRACS trial results. The LSCTC was a structured competency-based training
      programme designed to help develop the knowledge and skills (eg, patient handling
      or transfer skills) essential for the day-to-day management of disabled survivors
      of stroke. The LSCTC comprised 14 components, 6 were mandatory (and delivered to
      all) and 8 non-mandatory, to be delivered based on individual assessment of
      caregiver need. DESIGN: Process evaluation using non-participant observation,
      documentary analysis and semistructured interviews. PARTICIPANTS: Patients with
      stroke (n=38), caregivers (n=38), stroke unit staff (n=53). SETTINGS: 10 of the
      36 stroke units participating in the TRACS trial in four English regions
      (Yorkshire, North West, South East and South West, Peninsula). RESULTS:
      Preparatory cascade training on delivery of the LSCTC did not reach all staff and
      did not lead to multidisciplinary team (MDT) wide understanding of, engagement
      with or commitment to the LSCTC. Although senior therapists in most intervention
      units observed developed ownership of the LSCTC, MDT working led to separation
      rather than integration of delivery of LSCTC elements. Organisational features of
      stroke units and professionals' patient-focused practices limited the involvement
      of caregivers. Caregivers were often invited to observe therapy or care being
      provided by professionals but had few opportunities to make sense of, or to
      develop knowledge and stroke-specific skills provided by the LSCTC. Where
      provided, caregiver training came very late in the inpatient stay. Assessment and
      development of caregiver competence was not commonly observed. CONCLUSIONS:
      Contextual factors including service improvement pressures and staff perceptions
      of the necessity for and work required in caregiver training impacted negatively
      on implementation of the caregiver training intervention. Structured caregiver
      training programmes such as the LSCTC are unlikely to be practical in settings
      with short inpatient stays. Stroke units where early supported discharge is in
      place potentially offer a more effective vehicle for introducing competency based
      caregiver training. LINKED TRACS CLUSTER RANDOMISED CONTROLLED TRIAL NUMBER:
      ISRCTN49208824.

PMID- 24736036
TI  - Built environment and physical activity in New Zealand adolescents: a protocol
      for a cross-sectional study.
AB  - INTRODUCTION: Built-environment interventions have the potential to provide
      population-wide effects and the means for a sustained effect on behaviour change.
      Population-wide effects for adult physical activity have been shown with selected
      built environment attributes; however, the association between the built
      environment and adolescent health behaviours is less clear. This New Zealand
      study is part of an international project across 10 countries (International
      Physical Activity and the Environment Network-adolescents) that aims to
      characterise the links between built environment and adolescent health outcomes.
      METHODS AND ANALYSES: An observational, cross-sectional study of the associations
      between measures of the built environment with physical activity, sedentary
      behaviour, body size and social connectedness in 1600 New Zealand adolescents
      aged 12-18 years will be conducted in 2013-2014. Walkability and neighbourhood
      destination accessibility indices will be objectively measured using Geographic
      Information Systems (GIS). Physical activity and sedentary behaviours will be
      objectively measured using accelerometers over seven consecutive days. Body mass
      index will be calculated as weight divided by squared height. Demographics,
      socioeconomic status, active commuting behaviours and perceived neighbourhood
      walkability will be assessed using the Neighbourhood Environment Walkability
      Scale for Youth and psychosocial indicators. A web-based computer-assisted
      personal interview tool Visualisation and Evaluation of Route Itineraries, Travel
      Destinations, and Activity Spaces (VERITAS) and Global Positioning System (GPS)
      receivers will be used in a subsample of 300 participants. A qualitative research
      component will explore barriers and facilitators for physical activity in
      adolescents with respect to the built and social environment in a subsample of 80
      participants. ETHICS AND DISSEMINATION: The study received ethical approval from
      the Auckland University of Technology Ethics Committee (12/161). Data will be
      entered and stored into a secure (password protected) database. Only the named
      researchers will have access to the data. Data will be stored for 10 years and
      permanently destroyed thereafter. The results papers will be submitted for
      publication in peer-reviewed journals.

PMID- 24736037
TI  - Predicting sleep disordered breathing in outpatients with suspected OSA.
AB  - OBJECTIVE: To validate the utilities of Berlin, STOP and STOP-BANG
      Questionnaires, other patient characteristics, comorbidities, Epworth Sleepiness
      Scale (ESS), fractional exhaled nitric oxide (FENO) and blood markers for the
      prediction of sleep disordered breathing (SDB) on limited polygraphy. SETTING:
      North Glasgow Sleep Service (a tertiary referral centre). PARTICIPANTS: 129
      consecutive patients, aged >=16 years, referred to the sleep clinic for
      assessment of possible obstructive sleep apnoea. INTERVENTIONS: We selected cut
      points of apnoea hypopnoea index (AHI) of >=5 and >=15/h from their home
      polygraphy and determined associations of these with individual symptoms,
      questionnaire scores and other results. Receiver operating characteristic
      analysis and univariate and multivariate logistic regression were used to explore
      these. PRIMARY AND SECONDARY OUTCOMES MEASURES: Primary: The utility of STOP,
      STOP-BANG and Berlin Questionnaires for prediction of SDB. Secondary: The utility
      of other measures for prediction of SDB. RESULTS: AHI was >=5 in 97 patients and
      >=15 in 56 patients. STOP and STOP-BANG scores were associated with both AHI cut
      points but results with ESS and Berlin Questionnaire scores were negative. STOP
      BANG had a negative predictive value 1.00 (0.77-1.00) for an AHI >=15 with a
      score >=3 predicting AHI >=5 with sensitivity 0.93 (95% CI 0.84 to 0.98) and
      accuracy 79%, while a score >=6 predicted AHI >=15 with specificity 0.78 (0.65 to
      0.88) and accuracy 72%. Neck circumference >=17 inch and presence of witnessed
      apnoeas were independent predictors of SDB. CONCLUSIONS: STOP and STOP-BANG
      Questionnaires have utility for the prediction of SDB in the sleep clinic
      population. Modification of the STOP-BANG Questionnaire merits further study in
      this and other patient groups.

PMID- 24736038
TI  - Do rapid BMI growth in childhood and early-onset obesity offer cardiometabolic
      protection to obese adults in mid-life? Analysis of a longitudinal cohort study
      of Danish men.
AB  - OBJECTIVE: Some obese individuals have no cardiometabolic abnormalities; they are
      'metabolically healthy, but obese' (MHO). Similarly, some non-obese individuals
      have cardiometabolic abnormalities, that is, 'metabolically at risk, normal
      weight' (MANW). Previous studies have suggested that early-onset obesity may be
      associated with MHO. We aimed to assess whether body mass index (BMI) in
      childhood and early-onset obesity are associated with MHO. SETTING: General
      population longitudinal cohort study, Denmark. PARTICIPANTS: From 362 200 young
      men (mean age 20) examined for Danish national service between 1943 and 1977, all
      obese men (BMI >=31 kg/m(2), N=1930) were identified along with a random 1%
      sample of the others (N=3601). Our analysis includes 2392 of these men attending
      a research clinic in mid-life (mean age 42). For 613 of these men, data on
      childhood BMI are available. We summarised childhood BMI growth (7-13 years)
      using a multilevel model. Early-onset obesity was defined as obesity at
      examination for national service. OUTCOME MEASUREMENT: We defined metabolic
      health at the mid-life clinic as non-fasting serum cholesterol <6.6 mmol/L, non
      fasting glucose <8.39 mmol/L and pulse pressure <48 mm Hg. Participants were
      categorised into four groups according to their obesity (BMI >=30 kg/m(2)) and
      metabolic health in mid-life. RESULTS: 297 of 1097 (27.1%) of obese men were
      metabolically healthy; 826 of 1295 (63.8%) non-obese men had at least one
      metabolic abnormality. There was no evidence that rapid BMI growth in childhood
      or early-onset obesity was associated with either MHO or the MANW phenotype, for
      example, among obese men in mid-life, the OR for MHO comparing early-onset
      obesity with non-early-onset obesity was 0.97 (95% CI 0.85 to 1.10). CONCLUSIONS:
      We found no robust evidence that early-onset obesity or rapid BMI growth in
      childhood is protective for cardiometabolic health.

PMID- 24736040
TI  - Does early oral feeding increase the likelihood of salivary fistula after total
      laryngectomy?
AB  - Objective: This study compared the incidence of salivary fistula between groups
      with an early or late reintroduction of oral feeding, and identified the
      predictive factors for salivary fistula. Methods: A randomised trial was
      performed using 89 patients with larynx or hypopharynx cancer, assigned to 2
      groups (early or late). In the early group, oral feeding was started 24 hours
      after total laryngectomy or total pharyngolaryngectomy, and in the late group, it
      was started from post-operative day 7 onwards. The occurrence of salivary fistula
      was evaluated in relation to the following variables: early or late oral feeding,
      nutritional status, cancer stage, surgery performed, and type of neck dissection.
      Results: The incidence of salivary fistula was 27.3 per cent (n = 12) in the
      early group and 13.3 per cent (n = 6) in the late group (p = 0.10). The following
      variables were not statistically significant: nutritional status (p = 0.45);
      tumour location (p = 0.37); type of surgery (p = 0.91) and type of neck
      dissection (p = 0.62). A significant difference (p = 0.02) between the free
      margins and invasive carcinoma was observed. Conclusion: The early reintroduction
      of oral feeding in total laryngectomised patients did not increase the incidence
      of salivary fistula.

PMID- 24736039
TI  - How does family drug treatment court participation affect child welfare outcomes?
AB  - Parental substance use is a risk factor for child maltreatment. Family drug
      treatment courts (FDTCs) have emerged in the United States as a policy option to
      treat the underlying condition and promote family preservation. This study
      examines the effectiveness of FDTCs in North Carolina on child welfare outcomes.
      Data come from North Carolina records from child protection services, court
      system, and birth records. Three types of parental participation in a FDTC are
      considered: referral, enrolling, and completing an FDTC. The sample includes 566
      children who were placed into foster care and whose parents participated in a
      FDTC program. Findings indicate that children of parents who were referred but
      did not enroll or who enrolled but did not complete had longer stays in foster
      care than children of completers. Reunification rates for children of completers
      were also higher. Outcomes for children in the referred and enrolled groups did
      not differ in the multivariate analyses. While effective substance use treatment
      services for parents may help preserve families, future research should examine
      factors for improving participation and completion rates as well as factors
      involved in scaling programs so that more families are served. 

PMID- 24736041
TI  - Patterns of androgen deprivation therapies among men diagnosed with localised
      prostate cancer: a population-based study.
AB  - AIM: Many men diagnosed with localised prostate cancer will eventually be treated
      with androgen deprivation therapy (ADT). ADT is associated with adverse effects
      and its timing is controversial. Data on patterns of use are scarce. We describe
      patterns of ADT use, defined as castration (medical and surgical) or antiandrogen
      monotherapy initiated after primary treatment, in a population-based cohort.
      METHODS AND MATERIALS: Data were extracted from the population-based Prostate
      Cancer data Base Sweden (PCBaSe). Totally 45,147 men diagnosed between 1997 and
      2009 with clinical stage T1-2, N0-NX, M0-MX and prostate specific antigen
      (PSA)<50ng/ml without primary ADT were included. Outcomes in the period 2006
      through 2010 were analysed using a period analysis approach. RESULTS: The
      cumulative incidence of castration at 10years after diagnosis was 11.6% (95%
      confidence interval (CI), 11.0-12.2%). The corresponding proportion of
      antiandrogen monotherapy was 10.8% (95% CI, 10.2-11.4%). Castration was the
      dominant therapy among men on deferred treatment. The probability of receiving
      castration rather than antiandrogen monotherapy increased with age. Estimated
      median durations of castration ranged from 4years in the deferred treatment high
      risk group to 17years in the prostatectomy low-risk group. The main limitation
      was the lack of information on progression to metastatic disease and PSA at the
      time for initiation of ADT. CONCLUSION: When initiated early after curative
      treatment, the duration of castration can be decades. The findings indicate that
      more accurate tools are necessary to guide which men should be selected for ADT
      as secondary treatment.

PMID- 24736042
TI  - Tamiflu purchase worth L49m will go ahead, government says.

PMID- 24736044
TI  - Conformational changes of DNA in the presence of 12-s-12 gemini surfactants (s=2
      and 10). Role of the spacer's length in the interaction surfactant
      polynucleotide.
AB  - A multifaceted study on the interaction of calf-thymus DNA with two different
      cationic gemini surfactants alkanediyl-alpha-omega-bis(dodecyldimethyl
      amonium)bromide, 12-s-12,2Br(-) (with s=2, G2, and 10, G10) was carried out. The
      measurements were done at different molar ratios X=[surfactant]/[DNA]. Results
      show two different conformational changes in DNA: a first compaction of the
      polynucleotide corresponding to a partial conformational (not total) change of
      DNA from an extended coil state to a globular state that happens at the lower
      molar ratio X. A second change corresponds to a breaking of the partial
      condensation, that is, the transition from the compacted state to a new more
      extended conformation (for the higher X values) different to the initial
      extension. According to circular dichroism spectra and dynamic light scattering
      measurements, this new state of DNA seems to be similar to a psi-phase.
      Measurements confirm that interactions involved in the compaction are different
      to those previously obtained for the analog surfactant CTAB. X values at which
      the conformational changes happen depend on the length of the spacer in the
      surfactant along with the charge of the polar heads. 

PMID- 24736045
TI  - Diversity of rare and abundant bacteria in surface waters of the Southern
      Adriatic Sea.
AB  - Bacteria are fundamental players in the functioning of the ocean, yet relatively
      little is known about the diversity of bacterioplankton assemblages and the
      factors shaping their spatial distribution. We investigated the diversity and
      community composition of bacterioplankton in surface waters of the Southern
      Adriatic sub-basin (SAd) in the Mediterranean Sea, across an environmental
      gradient from coastal to offshore stations. Bacterioplankton diversity was
      investigated using a whole-assemblage genetic fingerprinting technique (Automated
      Ribosomal Intergenic Spacer Analysis, ARISA) coupled with 16S rDNA amplicon
      pyrosequencing. The main physico-chemical variables showed clear differences
      between coastal and offshore stations, with the latter displaying generally
      higher temperature, salinity and oxygen content. Bacterioplankton richness was
      higher in coastal than offshore waters. Bacterial community composition (BCC)
      differed significantly between coastal and offshore waters, and appeared to be
      influenced by temperature (explaining up to 30% of variance) and by the trophic
      state. Pyrosequencing evidenced dominance of Alphaproteobacteria (SAR11 cluster),
      uncultured Gammaproteobacteria (Rhodobacteraceae) and Cyanobacteria
      (Synechococcus). Members of the Bacteroidetes phylum were also abundant, and
      accounted for 25% in the station characterized by the higher organic carbon
      availability. Bacterioplankton assemblages included a few dominant taxa and a
      very large proportion (85%) of rare (<0.1%) bacteria, the vast majority of which
      was unique to each sampling station. The first detailed census of
      bacterioplankton taxa in the SAd sub-basin, performed using next generation
      sequencing, indicates that assemblages are highly heterogeneous, spatially
      structured according to the environmental conditions, and comprise a large number
      of rare taxa. The high turnover diversity, particularly evident at the level of
      the rare taxa, suggests to direct future investigations toward larger spatial or
      temporal scales, to better understand the role of bacterioplankton in the
      ecosystem functioning and the biogeochemistry of the basin. 

PMID- 24736046
TI  - Translocation of a nanoparticle through a fluidic channel: the role of grafted
      polymers.
AB  - The surface properties of nanoparticles (NPs) are key factors for their design
      and use in biomedicine; however, our understanding of the effect of surface
      properties on the translocation of NPs through membranes is still rather poor.
      Herein, we have used molecular dynamics simulations to study the translocation of
      a polymer-grafted NP through a fluidic channel. We change the length, number,
      amount of charge and the charge position of grafted polymers. With the increase
      of polymer length, the NP flux decreases as a whole due to the increase of NP
      size, where the -NP translocation fails at the smallest polymer length, because
      of the strong binding of Na(+). Surprisingly, the NP flux exhibits a maximum with
      the increase of the polymer number or charge amount, which is co-determined by
      the NP net charge and size. Owing to the NP-membrane adsorption and NP-ion
      binding, the NP flux decreases with the decrease of charge position. We also
      analyze the transport of counterions, which depends on both the NP-ion binding
      and NP dynamics. Finally, we investigate the effect of electric fields for a
      given NP type. Our results reveal the important role of grafted polymers in the
      NP translocation and may have implications in the design of highly efficient NP
      delivery. 

PMID- 24736047
TI  - Intractable Polyuria Mimicking Diabetes Insipidus-Source Traced to Vecuronium
      Infusion.
AB  - Continuous infusion of vecuronium is a commonly used technique for patients
      requiring prolonged neuromuscular blockade for mechanical ventilation. As
      compared with older neuromuscular blocking agents, it confers the advantages of
      rapid excretion and intermediate duration of action. Prolongation of
      neuromuscular blockade and muscle weakness are the known complications of
      continuous vecuronium infusion. This report attempts to describe polyuria, as a
      hitherto unknown complication of vecuronium infusion, which can occur due to the
      mannitol present in commercially available preparation of vecuronium bromide. 

PMID- 24736048
TI  - Linear synthesis and conformational analysis of the pentasaccharide repeating
      unit of the cell wall O-antigen of Escherichia coli O13.
AB  - Synthesis of the pentasaccharide repeating unit of the O-antigen of Escherichia
      coli O13 strain has been achieved using a straightforward linear synthetic
      strategy. Similar reaction conditions have been used for all glycosylations as
      well as protective group manipulations. All intermediate steps are high yielding
      and the glycosylation steps are stereoselective. The synthesized pentasaccharide
      was subjected to conformational analysis using 2D ROESY NMR spectral analysis and
      molecular dynamics (MD) simulation to get detailed information on conformation of
      the molecule in aqueous solution. 

PMID- 24736043
TI  - Neural innervation of white adipose tissue and the control of lipolysis.
AB  - White adipose tissue (WAT) is innervated by the sympathetic nervous system (SNS)
      and its activation is necessary for lipolysis. WAT parasympathetic innervation is
      not supported. Fully-executed SNS-norepinephrine (NE)-mediated WAT lipolysis is
      dependent on beta-adrenoceptor stimulation ultimately hinging on hormone
      sensitive lipase and perilipin A phosphorylation. WAT sympathetic drive is
      appropriately measured electrophysiologically and neurochemically (NE turnover)
      in non-human animals and this drive is fat pad-specific preventing
      generalizations among WAT depots and non-WAT organs. Leptin-triggered SNS
      mediated lipolysis is weakly supported, whereas insulin or adenosine inhibition
      of SNS/NE-mediated lipolysis is strongly supported. In addition to lipolysis
      control, increases or decreases in WAT SNS drive/NE inhibit and stimulate white
      adipocyte proliferation, respectively. WAT sensory nerves are of spinal-origin
      and sensitive to local leptin and increases in sympathetic drive, the latter
      implicating lipolysis. Transsynaptic viral tract tracers revealed WAT central
      sympathetic and sensory circuits including SNS-sensory feedback loops that may
      control lipolysis. 

PMID- 24736049
TI  - Orthostatic tremor: a review of 45 cases.
AB  - OBJECTIVE: To evaluate the clinical characteristics, associated features, and
      treatment response of a large orthostatic tremor series seen over a 26-year
      period. METHODS: We reviewed the medical records of 45 patients seen between 1987
      and 2013 who fulfilled the diagnostic criteria for orthostatic tremor. RESULTS:
      The mean age at onset was 59.5 years and 23/45 (51%) were men. A family history
      of any tremor was noted in 23/45 (51%) patients. A family history of orthostatic
      tremor was reported in 3/45 (7%) patients. 40/45 (89%) had primary orthostatic
      tremor with (n = 30) or without (n = 10) an associated postural arm tremor. We
      found that 5/45 (11%) had orthostatic tremor plus additional neurological
      features. One patient was diagnosed with dementia with Lewy bodies preceded by
      orthostatic tremor for 20 years. Prospective follow-up data was available for
      30/45 patients and averaged 54.4 months. Treatment response to medications was
      modest and inconsistent. In 11/30 cases, orthostatic tremor worsened over the
      follow-up period. One patient with primary orthostatic tremor underwent thalamic
      deep brain stimulation surgery. CONCLUSIONS: In our population of orthostatic
      tremor patients, mild postural hand tremor was a frequent finding. Over half of
      our patients had a family history of tremor, but a family history of orthostatic
      tremor was uncommon. Additional neurological features were seen in the minority
      of patients and we report possibly the first case of dementia with Lewy bodies
      associated with orthostatic tremor. Our series is the largest series of
      orthostatic tremor reported in the literature and contributes to understanding
      the clinical characteristics of this rare disease.

PMID- 24736050
TI  - Optic neuropathy induced by experimentally reduced cerebrospinal fluid pressure
      in monkeys.
AB  - PURPOSE: To examine the influence of experimentally reduced cerebrospinal fluid
      pressure (CSFP) on retinal nerve fiber layer (RNFL) thickness and neuroretinal
      rim area of the optic nerve head. METHODS: This experimental study included nine
      monkeys that underwent implantation of a lumbar-peritoneal cerebrospinal fluid
      (CSF) shunt. In the study group (n = 4 monkeys), the shunt was opened to achieve
      a CSF of approximately 40 mm H2O, while the shunt remained closed in the control
      group (n = 5 monkeys). At baseline and in monthly intervals thereafter, optical
      coherence tomographic and photographic images of the optic nerve head and RNFL
      were taken of all monkeys. RESULTS: Two out of four monkeys in the study group
      showed bilaterally a progressive reduction in RNFL thickness between 12% and 30%,
      reduction in neuroretinal rim area and volume, and increase in cup-to-disc area
      ratios. A third monkey developed a splinter-like disc hemorrhage in one eye. The
      fourth monkey in the study group did not develop morphologic changes during
      follow-up, nor did any monkey in the control group. CONCLUSIONS: Experimental and
      chronic reduction in CSF in monkeys was associated with the development of an
      optic neuropathy in some monkeys.

PMID- 24736051
TI  - Preservation of the photoreceptor layer following subthreshold laser treatment
      for diabetic macular edema as demonstrated by SD-OCT.
AB  - PURPOSE: Subthreshold laser treatment of diabetic macular edema (DME) may have
      less deleterious effects on the photoreceptors than regular continuous wave
      laser. This study aimed to assess whether subthreshold laser causes a long-term
      damage to the retinal structures, as demonstrated by spectral-domain optical
      coherence tomography (SD-OCT), and to evaluate the change in the axial diameter
      of retinal diabetic microaneurysms following treatment. METHODS: A retrospective
      study of eyes that were diagnosed with nonfoveal involving DME and underwent
      subthreshold laser treatment with the Novus SRT system. Spectral-domain OCT scans
      of treated retinal areas, performed prior to treatment and approximately 4 months
      following treatment, were assessed for changes in the continuity of the
      photoreceptor (PR) layer, the thickness of the PR-RPE layer, the retinal
      thickness at the treatment sites, and the diameter of the microaneurysms.
      RESULTS: Included in this study were 31 microaneurysms. Following treatment, the
      continuity of the ellipsoid zone of the inner segments of the photoreceptors was
      confirmed in all but two cases. The thickness of the PR-RPE layers was 72.32 +/-
      7.36 and 70.97 +/- 7.27 MUm prior to and following treatment, respectively (P =
      0.061). The retinal thickness at the treatment sites decreased from 398.65 +/-
      57.89 to 372.74 +/- 60.4 MUm (P < 0.001). The mean measured diameter of the
      microaneurysms was 87.32 +/- 27.45 and 6.68 +/- 26.12 MUm, respectively (P <
      0.001). CONCLUSIONS: In this study, subthreshold laser treatment for DME has been
      shown to be a safe technology that preserves the photoreceptor layer, as
      demonstrated by SD-OCT.

PMID- 24736052
TI  - Asymmetrical recovery of cone outer segment tips line and foveal displacement
      after successful macular hole surgery.
AB  - PURPOSE: To determine whether the photoreceptor outer segments recover
      symmetrically after successful macular hole surgery, and whether the recovery is
      correlated with the degree of foveal displacement. METHODS: This was a
      retrospective, interventional case series. The medical records of 35 patients (n
      = 35 eyes) with a surgically closed macular hole were reviewed. Spectral-domain
      optical coherence tomography (SD-OCT) was used to obtain cross-sectional images
      across the fovea horizontally and vertically. The lengths of cone outer segment
      tips (COST) line defect in the temporal, nasal, superior, and inferior sectors of
      the fovea, the best-corrected visual acuity (BCVA), and the papillofoveal
      distance were measured before and at 6 and 12 months after the surgery. RESULTS:
      The temporal COST line defect was significantly longer than the nasal length
      defect preoperatively (P = 0.031), at 6 months (P < 0.001), and at 12 months (P =
      0.038) postoperatively. The length of the temporal COST line defect was
      significantly correlated with the BCVA preoperatively (P = 0.014) and at 6 months
      postoperatively (P = 0.001). The papillofoveal distance was significantly shorter
      at 6 months (P = 0.029) and 12 months (P = 0.043) postoperatively than at the
      baseline. The center of the COST line defect was located further temporally from
      the fovea postoperatively, and the distance was shorter than the nasal foveal
      displacement at 6 months (158.8 +/- 167.0 MUm, P = 0.13) and 12 months (244.8 +/-
      172.7 MUm, P = 0.008). CONCLUSIONS: The restoration of the temporal COST line was
      delayed after successful macular hole surgery. In addition, the fovea was
      displaced more nasally than the center of the COST line defect which recovered
      centripetally. (ClinicalTrials.gov number, NCT01959776.).

PMID- 24736054
TI  - Potential new diagnostic tool for Alzheimer's disease using a linear discriminant
      function for Fourier domain optical coherence tomography.
AB  - PURPOSE: We calculated and validated a linear discriminant function (LDF) for
      Fourier domain optical coherence tomography (OCT) to improve the diagnostic
      ability of retinal and retinal nerve fiber layer (RNFL) thickness parameters in
      the detection of Alzheimer's disease (AD). METHODS: We enrolled AD patients (n =
      151) and age-matched, healthy subjects (n = 61). The Cirrus and Spectralis OCT
      systems were used to obtain retinal measurements and circumpapillary RNFL
      thickness for each participant. An LDF was calculated using all retinal and RNFL
      OCT measurements. Receiver operating characteristic (ROC) curves were plotted and
      compared among the LDF and the standard parameters provided by OCT devices.
      Sensitivity and specificity were used to evaluate diagnostic performance. A
      validating set was used in an independent population to test the performance of
      the LDF. RESULTS: The optimal function was calculated using the RNFL thickness
      provided by Spectralis OCT, using the 768 points registered during peripapillary
      scan acquisition (grouped to obtain 24 uniformly divided locations): 18.325 +
      0.056 * (315 degrees -330 degrees ) - 0.122 * (300 degrees -315 degrees ) - 0.041
      * (285 degrees -300 degrees ) + 0.091 * (255 degrees -270 degrees ) + 0.041 *
      (225 degrees -240 degrees ) + 0.183 * (195 degrees -210 degrees ) - 0.108 * (150
      degrees -165 degrees ) - 0.092 * (75 degrees -90 degrees ) + 0.051 * (30 degrees 
      45 degrees ). The largest area under the ROC curve was 0.967 for the LDF. At 95%
      fixed specificity, the LDF yielded the highest sensitivity values. CONCLUSIONS:
      Measurements of RNFL thickness obtained with the Spectralis OCT device
      differentiated between healthy and AD individuals. Based on the area under the
      ROC curve, the LDF was a better predictor than any single parameter.

PMID- 24736053
TI  - Early alteration of retinal neurons in Aipl1-/- animals.
AB  - PURPOSE: Mutations in the photoreceptor cell-specific gene encoding aryl
      hydrocarbon receptor-interacting protein-like 1 (AIPL1) lead to Leber congenital
      amaurosis (LCA4), retinitis pigmentosa, and cone-rod dystrophy. Gene therapy
      appears to be promising in the treatment for AIPL1-mediated vision loss in
      humans. Prior to initiating these treatments, however, it is crucial to
      understand how the retinal neurons remodel themselves in response to
      photoreceptor cell degeneration. In this study, using an animal model for AIPL1
      LCA, Aipl1(-/-) mice, we investigate the changes in postreceptoral retinal
      neurons during the course of photoreceptor cell loss. METHODS: Morphology of the
      Aipl1(-/-) retina from postnatal day 8 to 150 was compared to that of age
      matched, wild-type C57Bl6/J retina (WT) by immunocytochemistry using cell
      specific markers. RESULTS: Expression of postsynaptic proteins in bipolar cells
      is reduced prior to photoreceptor cell degeneration at postnatal day 8. Bipolar
      and horizontal cells retract their dendrites. Cell bodies and axons of bipolar
      and horizontal cells are disorganized during the course of degeneration. Muller
      cell processes become hypertrophic and form a dense fibrotic layer outside the
      inner nuclear layer. CONCLUSIONS: An early defect in photoreceptor cells in the
      AIPL1-LCA mouse model affects the expression of postsynaptic markers, suggesting
      abnormal development of bipolar synapses. Once degeneration of photoreceptor
      cells is initiated, remodeling of retinal neurons in the Aipl1(-/-) animal is
      rapid.

PMID- 24736055
TI  - Retinal oximetry with a scanning laser ophthalmoscope.
AB  - PURPOSE: The purpose of the study was to assess if a scanning laser
      ophthalmoscope (SLO), Optomap 200Tx, could be used for measurements of hemoglobin
      oxygen saturation in retinal blood vessels. METHODS: Optomap 200Tx uses two
      lasers for image acquisition, 532 and 633 nm. Retinal images of healthy
      individuals and patients with retinal vein occlusion were analyzed with modified
      Oxymap Analyzer software, which tracks retinal vessels and calculates relative
      hemoglobin oxygen saturation. RESULTS: Oxygen saturation in healthy individuals
      was measured as 92% +/- 13% for arterioles and 57% +/- 12% for venules (mean +/-
      SD, n = 11, P = 0.0001). Standard deviation for repeated measurements of the same
      eye was 3.5% for arterioles and 4.4% for venules. In patients with confirmed
      venular hypoxia, central retinal vein occlusion (CRVO) or hemivein occlusion, the
      average venular oxygen saturation was measured as 23% +/- 3% in the affected eyes
      and 59% +/- 3% in the fellow eyes (n = 4, P = 0.0009). CONCLUSIONS: Technically,
      it is possible to derive information on retinal oxygen saturation from an SLO
      with a 2-wavelength oximetry algorithm. The system produced both sensitive and
      repeatable results. The remaining challenges include decreasing variability
      between vessels of the same eye and variability between individuals. Given the
      advantages that SLO imaging has over conventional fundus camera optics in retinal
      oximetry, further development of SLO oximetry may provide the optimal approach to
      retinal oximetry.

PMID- 24736056
TI  - Large-scale imaginal disc sorting: A protocol for "omics"-approaches.
AB  - Imaginal discs, especially the wing imaginal disc, are powerful model systems to
      study organ development. The traditional methods to analyze wing imaginal discs
      depend on the laborious and time-consuming dissection of larvae. "Omics"-based
      approaches, such as RNA-seq, ChIP-seq, proteomics and lipidomics, offer new
      opportunities for the systems-level investigation of organ development. However,
      it is impractical to manually isolate the required starting material. This is
      even more problematic when experiments strive for enhanced temporal and spatial
      resolution. The mass isolation workflow discussed in this review, solves this
      problem. The semi-automated sorting of 1000 wing imaginal discs in less than 3h
      forms the basis of a workflow that can be connected to biochemical analyses of
      organ patterning and growth. In addition to the mass isolation workflow we
      briefly describe key "omics" technologies and their applications. The combination
      of mass isolation and "omics"-approaches ensures that the wing imaginal disc will
      continue to be a key model organ for studying developmental processes, both on
      the genetic, but increasingly also on the biochemical level. 

PMID- 24736057
TI  - Isolated trisomy 2 in bone marrows of patients with suspected hematopoietic
      malignancies.
AB  - Isolated trisomy 2 in hematopoietic malignancies is rare, having been reported in
      only eight cases. Of these cases, the majority are older males. The underlying
      hematologic malignancies range from myelodysplastic syndrome (MDS) to acute
      myeloid leukemia (AML). The molecular pathogenesis and prognostic significance of
      isolated trisomy 2 remains unknown. Herein, we report 11 cases of isolated
      trisomy 2 in hematologic disorders seen in the Mayo Clinic Cytogenetics
      laboratory from 1996-2012. The majority were older males between the ages of 63
      93 years. The underlying bone marrow pathologic diagnoses ranged from no
      diagnostic features of malignancy to AML. Our data suggest that isolated trisomy
      2 could represent an age-related phenomenon since all 11 cases were age 63 and
      over. It appears that isolated trisomy 2 harbors little prognostic significance
      and that, instead, the prognostic significance is driven by the underlying
      pathologic diagnosis. For example, whereas 3 of the cases with AML survived only
      7-10 weeks post-bone marrow biopsy, 1 of the cases without diagnostic features of
      malignancy survived 10 additional years. Therefore, trisomy 2 as a sole
      abnormality should not be considered as definitive evidence for a myeloid
      neoplasm in the absence of diagnostic morphologic criteria. 

PMID- 24736060
TI  - Mirror mirror on the wall, who is the fairest of them all.

PMID- 24736061
TI  - A nice problem to have: when ALK inhibitor therapy works better than expected.

PMID- 24736062
TI  - An era of lung cancer iconoclasts.

PMID- 24736063
TI  - E-cigarettes and cancer patients.
AB  - The increasing popularity and availability of electronic cigarettes (i.e., e
      cigarettes) in many countries have promoted debate among health professionals as
      to what to recommend to their patients who might be struggling to stop smoking or
      asking about e-cigarettes. In the absence of evidence-based guidelines for using
      e-cigarettes for smoking cessation, some health professionals have urged caution
      about recommending them due to the limited evidence of their safety and efficacy,
      while others have argued that e-cigarettes are obviously a better alternative to
      continued cigarette smoking and should be encouraged. The leadership of the
      International Association for the Study of Lung Cancer asked the Tobacco Control
      and Smoking Cessation Committee to formulate a statement on the use of e
      cigarettes by cancer patients to help guide clinical practice. Below is this
      statement, which we will update periodically as new evidence becomes available. 

PMID- 24736064
TI  - Adrenal metastases in lung cancer: clinical implications of a mathematical model.
AB  - Adrenal gland metastases are common in lung cancer. It is well recognized that
      aggressive treatment of solitary adrenal metastases leads to improved outcomes
      but the exact nature of adrenal deposits is not well understood. Controversy
      exists as to the routing of cancer cells to the adrenal gland with some believing
      that this transmission is lymphatic, in contrast to the more generally accepted
      theory of hematogenous spread. Recently published mathematical modeling of cancer
      progression strongly supports the lymphatic theory. With that in mind, we
      performed a literature review to look for biological plausibility of simulation
      results and believe that evidence supports the contention that metastases to the
      adrenal gland can be routed by means of lymphatic channels. This could explain
      improved survival for patients in whom solitary adrenal metastases are managed
      aggressively with surgical or radiation modalities. We are calling for clinical
      trials prospectively testing this hypothesis. 

PMID- 24736065
TI  - Facility characteristics and quality of lung cancer care in an integrated health
      care system.
AB  - INTRODUCTION: In a national, integrated health care system, we sought to identify
      facility-level attributes associated with better quality of lung cancer care.
      METHODS: Adherence to 23 quality indicators across four domains (Diagnosis and
      Staging, Treatment, Supportive Care, End-of-Life Care) was assessed through
      abstraction of electronic records from 4804 lung cancer patients diagnosed in
      2007 at 131 Veterans Health Administration facilities. Performance was reported
      as proportions of eligible patients fulfilling adherence criteria. With
      stratification of patients by stage, generalized estimating equations identified
      facility-level characteristics associated with performance by domain. RESULTS:
      Overall performance was high for the older (mean age 67.7 years, SD 9.4 years),
      predominantly male (98%) veterans. However, no facility did well on every
      measure, and range of adherence across facilities was large; 9% of facilities
      were in the highest quartile for one or more domain of care, more than 30% for
      two, and 65% for three. No facility performed consistently well across all
      domains. Less than 1% performed in the lowest quartile for all. Few facility
      level characteristics were associated with care quality. For End-of-Life Care,
      diagnosis and treatment within the same facility, availability of cancer
      psychiatry/psychology consultation services, and availability of both inpatient
      and outpatient palliative care consultation services were associated with better
      adherence. CONCLUSIONS: Quality of Veterans Health Administration lung cancer
      care is generally high, though substantial variation exists across facilities.
      With the exception of the salutary impact of palliative care consultation
      services on end-of-life quality of care, observed facility-level characteristics
      did not consistently predict adherence to indicators, suggesting quality may be
      determined by complex local factors that are difficult to measure.

PMID- 24736067
TI  - ALK status testing in non-small-cell lung carcinoma by FISH on ThinPrep slides
      with cytology material.
AB  - INTRODUCTION: Oncogenic anaplastic lymphoma kinase (ALK) gene rearrangements in
      non-small-cell lung carcinomas (NSCLC) provide the basis for targeted therapy
      with crizotinib and other specific ALK inhibitors. Treatment eligibility is
      conventionally determined by the Food and Drug Administration-approved companion
      diagnostic fluorescence in situ hybridization (FISH) assay on paraffin-embedded
      tissue (PET). On limited samples such as fine needle aspiration-derived
      cytoblocks, FISH for ALK is often uninformative. FISH performed on liquid-based
      ThinPrep slides (ThinPrep-FISH) may represent a robust alternative. METHODS: Two
      hundred thirty cytology samples from 217 patients with advanced NSCLC, including
      a consecutive series of 179 specimens, were used to generate matched ThinPrep
      slides and paraffin cytoblocks. The same ThinPrep slides used for cytologic
      diagnosis were assessed by standard ALK break-apart two-color probe FISH, after
      etching of tumor areas. Ultrasensitive ALK immunohistochemistry (IHC) on
      corresponding cytoblocks [D5F3 antibody, OptiView signal amplification] served as
      the reference data set. RESULTS: ThinPrep-FISH ALK signals were robust in 228 of
      230 cases and not compromised by nuclear truncation inherent in paraffin-embedded
      tissue-FISH; only two samples displayed no signals. Nine of 178 informative cases
      (5%) in the consecutive series and 18 of 228 informative cases (7.8%) overall
      were ALK rearranged by ThinPrep-FISH. In 154 informative matched ThinPrep-FISH
      and cytoblock-IHC samples, 152 were concordant (10, 6.5% ALK status positive;
      142, 92.2% ALK status negative), and two (1.3%) were ThinPrep-FISH positive but
      IHC negative (sensitivity 100%, specificity 98.6%, overall agreement 98.7%).
      CONCLUSION: Detection of ALK gene rearrangements in liquid cytology ThinPrep
      slides derived from patients with NSCLC can be confidently used for clinical ALK
      molecular testing.

PMID- 24736066
TI  - Hereditary lung cancer syndrome targets never smokers with germline EGFR gene
      T790M mutations.
AB  - INTRODUCTION: Hereditary lung cancer syndromes are rare, and T790M germline
      mutations of the epidermal growth factor receptor (EGFR) gene predispose to the
      development of lung cancer. The goal of this study was to determine the clinical
      features and smoking status of lung cancer cases and unaffected family members
      with this germline mutation and to estimate its incidence and penetrance.
      METHODS: We studied a family with germline T790M mutations over five generations
      (14 individuals) and combined our observations with data obtained from a
      literature search (15 individuals). RESULTS: T790M germline mutations occurred in
      approximately 1% of non-small-cell lung cancer cases and in less than one in 7500
      subjects without lung cancer. Both sporadic and germline T790M mutations were
      predominantly adenocarcinomas, favored female gender, and were occasionally
      multifocal. Of lung cancer tumors arising in T790M germline mutation carriers,
      73% contained a second activating EGFR gene mutation. Inheritance was dominant.
      The odds ratio that T790M germline carriers who are smokers will develop lung
      cancer compared with never smoker carriers was 0.31 (p = 6.0E-05). There was an
      overrepresentation of never smokers with lung cancer with this mutation compared
      with the general lung cancer population (p = 7.4E-06). CONCLUSION: Germline T790M
      mutations result in a unique hereditary lung cancer syndrome that targets never
      smokers, with a preliminary estimate of 31% risk for lung cancer in never smoker
      carriers, and this risk may be lower for heavy smokers. The resultant cancers
      share several features and differences with lung cancers containing sporadic EGFR
      mutations.

PMID- 24736068
TI  - Predictive value of one-dimensional mean computed tomography value of ground
      glass opacity on high-resolution images for the possibility of future change.
AB  - OBJECTIVES: The purpose of this study was to evaluate the relationship between
      clinical and radiological findings and the progression of ground-glass opacity
      (GGO) and to identify risk factors that predict the outcome of pure GGO lesions.
      METHODS: A retrospective study was conducted on 63 nodules of pure GGO. Clinical
      characteristics, the largest diameter, shape, and marginal characteristics, and
      one-dimensional mean computed tomography (m-CT) value of the GGO lesions were
      evaluated. During follow-up, 12 GGO lesions increased in size, and 17 appeared as
      solid portion. These 29 lesions were classified as growth group, and the
      remaining 34 lesions as stable group. RESULTS: The m-CT values were -634.9 +/-
      15.3 and -712.1 +/- 14.1 HU for the growth and stable groups, respectively. The
      growth group was strongly associated with high m-CT values (p = 0.0007) and a
      history of lung cancer (p = 0.0389), whereas association with smoking habits and
      the shape of the GGO nodules was marginal. The m-CT values and a history of lung
      cancer were independent predictors for future changes in GGO lesions (p = 0.0023
      and p = 0.0129, respectively). Sixteen of 18 lesions (88.9%) in patients without
      a history of lung cancer and with low m-CT values showed no nodule changes.
      CONCLUSIONS: The m-CT value of GGO lesions is a risk factor associated with their
      future change. The interval of follow-up CT scanning or treatment policy should
      be determined considering the m-CT value.

PMID- 24736070
TI  - Clinical significance of BIM deletion polymorphism in non-small-cell lung cancer
      with epidermal growth factor receptor mutation.
AB  - BACKGROUND: Germline alterations in the proapoptotic protein Bcl-2-like 11 (BIM)
      can have a crucial role in tumor response to treatment. To determine the clinical
      utility of detecting BIM deletion polymorphism in non-small-cell lung cancer
      positive for epidermal growth factor receptor (EGFR) mutation, we examined
      outcomes of patients with and without BIM alterations. METHODS: We studied 70
      patients with EGFR mutation-positive non-small-cell lung cancer who were treated
      with an EGFR tyrosine kinase inhibitor between January 2008 and January 2013. BIM
      deletion was analyzed by polymerase chain reaction in 58 samples of peripheral
      blood and 24 formalin-fixed paraffin-embedded slides of surgical specimens (20 of
      lung tissue and four of brain tissue); both blood and tissue specimens were
      available for 12 patients. We retrospectively analyzed clinical characteristics,
      response rate, toxicity, and outcomes among patients with and without BIM
      deletion. RESULTS: BIM deletion was present in 13 of 70 patients (18.6%). There
      were no significant differences between patients with and without BIM deletion in
      clinical characteristics, rate of response to EGFR tyrosine kinase inhibitor, or
      incidence of adverse events. Patients with BIM deletion had significantly shorter
      progression-free survival (PFS) than those without BIM deletion (median, 227
      versus 533 days; p < 0.001). Multivariate Cox regression analysis showed that BIM
      deletion was an independent indicator of shorter PFS (hazard ratio, 3.99; 95%
      confidence interval, 1.864-8.547; p < 0.001). CONCLUSIONS: Polymerase chain
      reaction successfully detected BIM deletion in samples of peripheral blood and
      formalin-fixed paraffin-embedded slides of surgical specimens. BIM deletion was
      the most important independent prognostic factor in shorter PFS.

PMID- 24736069
TI  - Epigenetic regulation of vitamin D metabolism in human lung adenocarcinoma.
AB  - INTRODUCTION: 1alpha,25-Dihydroxyvitamin D3 (1,25-D3) is antiproliferative in
      preclinical models of lung cancer, but in tumor tissues, its efficacy may be
      limited by CYP24A1 expression. CYP24A1 is the rate limiting catabolic enzyme for
      1,25-D3 and is overexpressed in human lung adenocarcinoma (AC) by unknown
      mechanisms. METHODS: The DNA methylation status of CYP24A1 was determined by
      bisulfite DNA pyrosequencing in a panel of 30 lung cell lines and 90 surgically
      resected lung AC. The level of CYP24A1 methylation was correlated with CYP24A1
      expression in lung AC cell lines and tumors. In addition, histone modifications
      were assessed by quantitative chromatin immunoprecipitation-polymerase chain
      reaction (ChIP-qPCR) in A549, NCI-H460, and SK-LU-1. RESULTS: Bisulfite DNA
      pyrosequencing analysis revealed that CYP24A1 gene was heterogeneously methylated
      in lung AC. Expression of CYP24A1 was inversely correlated with promoter DNA
      methylation in lung AC cell lines and tumors. Treatment with 5-aza-2'
      deoxycytidine (5-Aza) and trichostatin A (TSA) increased CYP24A1 expression in
      lung AC. We observed that CYP24A1 promoter hypermethylation decreased CYP24A1
      enzyme activity in vitro, whereas treatment with 5-Aza and/or TSA increased
      CYP24A1 enzyme affinity for its substrate 1,25-D3. In addition, ChIP-qPCR
      analysis revealed specific histone modifications within the CYP24A1 promoter
      region. Treatment with TSA increased H3K4me2 and H3K9ac and simultaneously
      decreased H3K9me2 at the CYP24A1 promoter and treatment with 5-Aza and/or TSA
      increased the recruitment of vitamin D receptor (VDR) to vitamin D response
      elements (VDRE) of the CYP24A1 promoter. CONCLUSIONS: The expression of CYP24A1
      gene in human lung AC is in part epigenetically regulated by promoter DNA
      methylation and repressive histone modifications. These findings should be taken
      into consideration when targeting CYP24A1 to optimize antiproliferative effects
      of 1,25-D3 in lung AC.

PMID- 24736071
TI  - Signal transducer and activator of transcription 3 as molecular therapy for non
      small-cell lung cancer.
AB  - INTRODUCTION: Targeting signal transducer and activator of transcription 3
      (STAT3), a transcription factor that modulates survival-directed transcription,
      is often persistently activated in epidermal growth factor receptor (EGFR) wild
      type non-small-cell lung cancer (NSCLC). The aim of this study was to determine
      whether sorafenib and its derivative can inhibit EGFR wild-type NSCLC via STAT3
      inactivation. METHODS: EGFR wild-type NSCLC cell lines (A549 H292 H322 H358 and
      H460) were treated with sorafenib or SC-1, a sorafenib derivative that closely
      resembled sorafenib structurally but was devoid of kinase inhibitory activity.
      Apoptosis and signal transduction were analyzed. In vivo efficacy was determined
      in nude mice with H460 and A549 xenograft. RESULTS: SC-1 had better effects than
      sorafenib on growth inhibition and apoptosis in all tested EGFR wild-type NSCLC
      lines. SC-1 reduced STAT3 phosphorylation at tyrosine 705 in all tested EGFR wild
      type NSCLC cells. The expression of STAT3-driven genes, including cylcin D1 and
      survivin, was also repressed by SC-1. Ectopic expression of STAT3 in H460 cells
      abolished apoptosis in SC-1-treated cells. Sorafenib and SC-1 enhanced Src
      homology-2 containing protein tyrosine phosphatase-1 (SHP-1) activity, whereas
      knockdown of SHP-1, but not SHP-2 or protein-tyrosine phosphatase 1B (PTP-1B), by
      small interference RNA reduced SC-1-induced apoptosis. SC-1 significantly reduced
      H460 and A549 tumor growth in vivo through SHP-1/STAT3 pathway. CONCLUSIONS: SC-1
      provides proof that targeting STAT3 signaling pathway may be a novel approach for
      the treatment of EGFR wild-type NSCLC.

PMID- 24736072
TI  - Prognostic impact of paraneoplastic cushing's syndrome in small-cell lung cancer.
AB  - INTRODUCTION: Paraneoplastic Cushing's syndrome (CushingPS) in small-cell lung
      cancer is rare but severe. METHODS: We studied 383 patients with small-cell lung
      cancer diagnosed between 1998 and 2012. Among them, 23 patients had CushingPS, 56
      had other paraneoplastic syndrome (OtherPS), and 304 had no paraneoplastic
      syndrome (NoPS). RESULTS: After comparison of the three groups, we observed that
      CushingPS patients had more extensive disease: 82.6% versus 67.8% versus 53.3% (p
      = 0.005), respectively, with more than two metastatic sites: 63.2% versus 15.8%
      and 24.1% (p <= 0.001), a higher World Health Organization performance status (2
      4): 73.9% versus 57.1% versus 43.7% (p = 0.006), greater weight loss (>=10%):
      47.8% versus 33.9% versus 16.4% (p <= 0.001), reduced objective response to first
      line treatment: 47.6% versus 74.1% versus 71.1% (p = 0.04), and poorer
      sensitivity to first-line treatment: 19% versus 38.9% versus 48.6% (p = 0.01).
      NoPS patients, with World Health Organization performance status of 3-4, had
      extensive disease at diagnosis, with response, sensitivity to first-line
      treatment, and survival similar to the CushingPS group. At relapse, the CushingPS
      group had no objective response to second-line treatment versus 25% versus 42.8%
      in OtherPS and NoPS groups, respectively (p = 0.005). The median survival of
      CushingPS patients was 6.6 months versus 9.2 months for OtherPS and 13.1 months
      for NoPS patients (p <= 0.001). CushingPS is a prognostic factor of death (hazard
      ratio, 2.31; p <= 0.001). CONCLUSION: CushingPS is the worst form of the
      paraneoplastic syndromes with particularly extensive tumors. Reduced objective
      response and sensitivity to first-line treatment and no response to second-line
      treatment suggest starting palliative care early at first line and exclusively at
      relapse.

PMID- 24736073
TI  - Comparison of clinical outcomes following gefitinib and erlotinib treatment in
      non-small-cell lung cancer patients harboring an epidermal growth factor receptor
      mutation in either exon 19 or 21.
AB  - BACKGROUND: Gefitinib and erlotinib, small-molecule kinase inhibitors that block
      epidermal growth factor receptor (EGFR) signaling, have demonstrated a dramatic
      response rate and prolonged progression-free survival (PFS) in patients harboring
      an activating EGFR mutation. We compared the clinical outcomes in gefitinib- and
      erlotinib-treated patients harboring EGFR mutations who had recurrent or
      metastatic non-small-cell lung cancer (NSCLC). METHODS: A total of 375 patients
      with recurrent or metastatic stage IIIB/IV NSCLC, who had either exon 19 deletion
      or the L858R mutation in exon 21, and had received either gefitinib (n = 228) or
      erlotinib (n = 147), were included in the study. A matched-pair case-control
      study design was implemented in the analysis, where 121 pairs of gefitinib
      treated and erlotinib-treated patients were matched according to sex, smoking
      history, Eastern Cooperative Oncology Group performance status, and types of EGFR
      mutation. RESULTS: The median age of all patients was 58 years (range, 30-84),
      and more than half of patients had never been smokers (63.6%). Most patients had
      adenocarcinoma (98.3%) and good Eastern Cooperative Oncology Group performance
      status (0, 1) (90.9%). The median number of cycles of EGFR tyrosine kinase
      inhibitor (TKI) treatment was 12.7 in the gefitinib group and 10.8 in the
      erlotinib group. Of the 242 patients, 63 (26%) received EGFR TKI as first-line
      therapy. The overall response rates and disease control rates in the gefitinib-
      or erlotinib-treated groups were 76.9% versus 74.4% (p = 0.575) and 90.1% versus
      86.8%, respectively (p = 0.305). There was no statistically significant
      difference with regard to PFS (median, 11.7 versus 9.6; p = 0.056) between the
      gefitinib- and erlotinib-treated groups. For patients receiving EGFR TKI as the
      first-line treatment, there was no significant difference between the two
      treatment groups in overall response rates (76.7% and 90.0%) (p = 0.431) and
      median PFS (11.7 versus 14.5 months) (p = 0.507). CONCLUSION: In NSCLC patients
      harboring EGFR mutation, treatment with gefitinib and erlotinib resulted in
      similar effectiveness.

PMID- 24736074
TI  - Redistribution of health care costs after the adoption of positron emission
      tomography among medicare beneficiaries with non-small-cell lung cancer, 1998
      2005.
AB  - INTRODUCTION: Treatment patterns and cost implications of increased positron
      emission tomography imaging use since Medicare approval in 1998 are not well
      understood. We examined rates of surgery, radiotherapy, and chemotherapy and
      inpatient and total health care costs between 1998 and 2005 among Medicare
      beneficiaries with non-small-cell lung cancer. METHODS: Patients in this
      retrospective cohort study were 51,374 Medicare beneficiaries diagnosed with non
      small-cell lung cancer between 1996 and 2005. The main outcome measures were
      receipt of surgical resection, radiotherapy, and chemotherapy and inpatient and
      total health care costs within 1 year of diagnosis. RESULTS: Between 1996-1997
      and 2004-2005, the proportion of patients undergoing surgical resection decreased
      from 29% to 25%, the proportion receiving radiation therapy decreased from 49% to
      43%, and inpatient costs decreased from $28,900 to $26,900. The proportion of
      patients receiving chemotherapy increased from 25% to 40% and total costs
      increased from $47,300 to $52,200 (p < 0.001 for all comparisons). Changes in use
      and costs remained after adjustment for shifting demographic characteristics
      during the study period. CONCLUSIONS: Adoption of positron emission tomography
      between 1998 and 2005 was accompanied by decreases in rates of surgery and
      radiotherapy and in short-term inpatient costs among Medicare beneficiaries with
      non-small-cell lung cancer, although there was an increase in chemotherapy and
      overall costs.

PMID- 24736075
TI  - Glucocorticoid receptor status is a principal determinant of variability in the
      sensitivity of non-small-cell lung cancer cells to pemetrexed.
AB  - INTRODUCTION: Pemetrexed is an S-phase targeted drug in front-line or maintenance
      therapy of advanced nonsquamous non-small-cell lung cancer (NSCLC) but methods
      are needed for predicting the drug response. Dexamethasone is typically
      administered the day before, the day of, and the day after pemetrexed. As
      dexamethasone strongly regulates many genes including p53 through the
      glucocorticoid receptor (GR), we hypothesized that dexamethasone influences tumor
      response to pemetrexed. METHODS: Eight nonsquamous NSCLC cell line models with
      varied p53 and GRalpha/GRbeta status were used for gene expression and cell-cycle
      analyses and for loss- or gain-of-function experiments. RESULTS: In three cell
      lines dexamethasone profoundly, but reversibly, suppressed the fraction of S
      phase cells. Dexamethasone also reversibly repressed expression of thymidylate
      synthase and dihydrofolate reductase, which are primary targets of pemetrexed but
      are also quintessential S-phase enzymes as well as the S-phase-dependent
      expression of thymidine kinase 1. Dexamethasone also decreased expression of the
      major pemetrexed transporters, the reduced folate carrier and the proton coupled
      folate transporter. Only cells expressing relatively high GRalpha showed these
      dexamethasone effects, regardless of p53 status. In cells expressing low GRalpha,
      the dexamethasone response was rescued by ectopic GRalpha. Further, depletion of
      p53 did not attenuate the dexamethasone effects. The presence of dexamethasone
      during pemetrexed treatment protected against pemetrexed cytotoxicity in only the
      dexamethasone responsive cells. CONCLUSIONS: The results predict that in
      nonsquamous NSCLC tumors, reversible S-phase suppression by dexamethasone,
      possibly combined with a reduction in the drug transporters, attenuates
      responsiveness to pemetrexed and that GR status is a principal determinant of
      tumor variability of this response.

PMID- 24736076
TI  - The impact of peer review of volume delineation in stereotactic body radiation
      therapy planning for primary lung cancer: a multicenter quality assurance study.
AB  - INTRODUCTION: Although the value of peer review is increasingly recognized, there
      is little research documenting its impact in the setting of stereotactic body
      radiation therapy (SBRT) for lung cancer. This study determines the dosimetric
      effect of peer review of tumor and normal tissue contouring in lung SBRT
      planning. METHODS: Forty anonymized lung SBRT plans were retrospectively
      evaluated post treatment. Each plan was independently reviewed by two to three
      radiation oncologists using established institutional guidelines. For each
      structure, reviewers recorded recommendations for "no change," "minor change,"
      "major change," or "missing contour" and provided a modified or new contour as
      needed. Dose-volume histograms were analyzed for dosimetric violations. RESULTS:
      Among 472 contoured structures evaluated, recommendations from peer review were
      107 major change (23%), 176 minor change (37%), 157 no change (33%), and 32
      missing (7%). Common major changes involved the skin (n = 20), heart (n = 18),
      and proximal bronchial tree (n = 15). Dose constraints were not achieved for 25
      new or recontoured structures (5%), of which 17 involved the planning target
      volume (PTV). Among cases with PTV violations, the mean prescription dose
      coverage to the modified PTVs was 90%, compared with the protocol standard of
      greater than or equal to 95% coverage. The remaining violations involved the ribs
      (n = 5), spinal canal (n = 2), and heart (n = 1). CONCLUSIONS: Peer review of
      structure contouring resulted in significant changes in lung SBRT plans.
      Recontouring of several plans revealed violations of dose limits, most often
      involving inadequate PTV coverage. Peer review, especially of target volume
      delineation, is warranted to improve consistency and quality in lung SBRT
      planning.

PMID- 24736077
TI  - Influence of preoperative radiation field on postoperative leak rates in
      esophageal cancer patients after trimodality therapy.
AB  - INTRODUCTION: Postoperative morbidities, such as anastomotic leaks, are common
      after trimodality therapy (chemoradiation followed by surgery) for esophageal
      cancer. We investigated for factors associated with an increased incidence of
      anastomotic leaks. METHODS: Data from 285 esophageal cancer patients treated from
      2000 to 2011 with trimodality therapy were analyzed. Anastomotic location
      relative to preoperative radiation field was assessed using postoperative
      computed tomographic imaging. Logistic regression was used to evaluate for
      factors associated with any or clinically relevant (CR) (>= grade 2) leaks.
      RESULTS: Overall anastomotic leak rate was 11% (31 of 285), and CR leak rate was
      6% (17 of 285). Multivariable analysis identified body mass index (odds ratio
      [OR], 1.09; 95% confidence interval [CI], 1.00-1.17; OR, 1.11, 95% CI, 1.01
      1.22), three-field surgery (OR, 10.01; 95% CI, 3.83-26.21; OR, 4.83; 95% CI, 1.39
      16.71), and within radiation field ("in-field") anastomosis (OR, 5.37; 95% CI,
      2.21-13.04; OR, 8.63; 95% CI, 2.90-25.65) as independent predictors of both all
      grade and CR leaks, respectively. While patients with distal esophageal tumors
      and Ivor-Lewis surgery had the lowest incidence of all grade (6.5%) and CR leaks
      (4.2%), most of the leaks were associated with the anastomosis constructed within
      the field of radiation (in-field: 39% and 30% versus out-of-field: 2.6% and 1.0%,
      respectively, for total and CR leaks, p less than 0.0001, Fisher's exact test).
      CONCLUSIONS: Esophagogastric anastomosis placed within the preoperative radiation
      field was a very strong predictor for anastomotic leaks in esophageal cancer
      patients treated with trimodality therapy, among other factors. Surgical planning
      should include a critical evaluation of the preoperative radiation fields to
      ensure proper anastomotic placement after chemoradiation therapy.

PMID- 24736078
TI  - Thymic carcinoma: a cohort study of patients from the European society of
      thoracic surgeons database.
AB  - INTRODUCTION: Thymic carcinoma is a rare and aggressive thymic neoplasm. The
      European Society of Thoracic Surgeons developed a retrospective database
      collecting patients undergoing resection for thymic tumors from 1990 to 2010.
      METHODS: Of 2265 patients with thymic tumors, there were 229 thymic carcinomas.
      Clinicopathological characteristics were analyzed including age, associated
      paraneoplastic diseases, stage (Masaoka-Koga), World Health Organization
      histologic subtypes, type of resection (total/subtotal/biopsy/no resection),
      tumor size, pre/postoperative treatments, and recurrence. Outcome measures
      included overall survival (OS), freedom from recurrence, and cumulative incidence
      of recurrence. RESULTS: A complete resection was achieved in 140 patients (69%).
      Recurrence occurred in 54 patients (28%). Five- and 10-year OS rates were 0.61
      and 0.37. Five- and 10-year freedom from recurrence rates were 0.60 and 0.43.
      Cumulative incidence of recurrence was 0.21 (3 yr), 0.27 (5 yr), and 0.32 (10
      yr). Survival was better after surgical resection versus biopsy/no resection (p <
      0.001), after complete resection versus subtotal resection (p < 0.001), and when
      using Masaoka-Koga system (stages I-II versus III versus IV) (p < 0.001). The use
      of multidisciplinary treatments resulted in a survival advantage which was
      significant in the surgery + radiotherapy group (p = 0.02). Incomplete resection
      (p < 0.0001) and advanced stage (Masaoka-Koga III-IV) (p = 0.02) had a negative
      impact on OS at multivariable analysis. Administration of adjuvant radiotherapy
      was beneficial in increasing OS (p = 0.02). CONCLUSIONS: The results of our study
      indicate that patients with thymic carcinoma should undertake surgical resection
      whenever possible; a complete resection and early Masaoka-Koga stage are
      independent predictors of improved survival; our results also suggest that
      postoperative radiotherapy is beneficial in improving survival.

PMID- 24736079
TI  - Next-generation sequencing reveals a Novel NSCLC ALK F1174V mutation and confirms
      ALK G1202R mutation confers high-level resistance to alectinib
      (CH5424802/RO5424802) in ALK-rearranged NSCLC patients who progressed on
      crizotinib.
AB  - Acquired secondary mutations in the anaplastic lymphoma kinase (ALK) gene have
      been identified in ALK-rearranged (ALK+) non-small-cell lung cancer (NSCLC)
      patients who developed disease progression while on crizotinib treatment. Here,
      we identified a novel secondary acquired NSCLC ALK F1174V mutation by
      comprehensive next-generation sequencing in one ALK+ NSCLC patient who progressed
      on crizotinib after a prolonged partial response to crizotinib. In a second case,
      we identified a secondary acquired ALK G1202R, which also confers resistance to
      alectinib (CH5424802/RO5424802), a second-generation ALK inhibitor that can
      inhibit ALK gatekeeper L1196M mutation in vitro. ALK G1202R is located at the
      solvent front of the ALK kinase domain and exhibits a high level of resistance to
      all other ALK inhibitors currently in clinical development in vitro.
      Comprehensive genomic profiling of resistant tumor is increasingly important in
      tailoring treatment decisions after disease progression on crizotinib in ALK+
      NSCLC given the promise of second-generation ALK inhibitors and other therapeutic
      strategies. 

PMID- 24736080
TI  - Germline EGFR T790M mutation found in multiple members of a familial cohort.
AB  - Activating mutations in epidermal growth factor receptor (EGFR) are present in a
      subset of lung cancers, and predict sensitivity to EGFR tyrosine kinase
      inhibitors. Acquisition of EGFR T790M is the most common mechanism of resistance
      to EGFR tyrosine kinase inhibitors and rarely is seen before treatment. Germline
      EGFR T790M mutations have been reported, although the penetrance and clinical
      significance of this mutation is unknown. We describe the identification of a
      patient with an EGFR T790M germline mutation and subsequent germline testing in
      her unaffected family members. Genetic testing revealed two additional EGFR T790M
      germline carriers, one of which was subsequently diagnosed with metastatic lung
      adenocarcinoma. 

PMID- 24736081
TI  - Phase II study of bendamustine in relapsed chemotherapy sensitive or resistant
      small-cell lung cancer.
AB  - INTRODUCTION: To determine the time to progression (TTP), response rate (RR), and
      toxicity for North American patients with relapsed small-cell lung cancer (SCLC)
      treated with bendamustine in the second- or third-line setting. METHODS: Patients
      with relapsed, histologically confirmed SCLC were eligible for enrollment on
      study. The study population included patients with both chemotherapy-sensitive
      and chemotherapy-resistant disease treated with up to two prior lines of
      chemotherapy. Patients were treated with 120 mg/m of bendamustine on days 1 and 2
      of a 21-day cycle for up to six cycles. Primary end point was TTP; secondary end
      points included toxicity, RR, and overall survival. RESULTS: Fifty-nine patients
      were accrued, 50 patients met eligibility for enrollment. The median age of
      patients was 62, and 56% were men. Twenty-nine patients (58%) had chemotherapy
      sensitive disease. Median TTP was 4.0 months (95% confidence interval [CI], 3.3
      5.4), median overall survival was 4.8 months (95% CI, 3.8-6.3), and the RR was
      26% (95% CI, 13.3%-39.5%). Patients with chemosensitive disease had a median TTP
      of 4.2 months (95% CI, 3.3-6.0) compared with 3.4 months (95% CI, 2.7-infinity)
      for chemotherapy-resistant disease. The RR was 33% (95% CI, 14.2%-51.8%) in
      patients with chemosensitive disease and 17% (95% CI, 0%-34.4%) in those with
      chemoresistant disease. The most common grade 3/4 adverse events were fatigue
      (20%), dyspnea (12%), and anemia (12%). CONCLUSION: Bendamustine has modest
      activity in relapsed SCLC similar to other agents evaluated in this patient
      population.

PMID- 24736082
TI  - A novel fusion of TPR and ALK in lung adenocarcinoma.
AB  - INTRODUCTION: Anaplastic lymphoma kinase (ALK) fusion is the most common
      mechanism for overexpression and activation in non-small-cell lung carcinoma.
      Several fusion partners of ALK have been reported, including echinoderm
      microtubule-associated protein-like 4, TRK-fused gene, kinesin family member 5B,
      kinesin light chain 1 (KLC1), protein tyrosine phosphatase and nonreceptor type
      3, and huntingtin interacting protein 1 (HIP1). METHODS AND RESULTS: A 60-year
      old Korean man had a lung mass which was a poorly differentiated adenocarcinoma
      with ALK overexpression. By using an Anchored Multiplex polymerase chain reaction
      assay and sequencing, we found that tumor had a novel translocated promoter
      region (TPR)-ALK fusion. The fusion transcript was generated from an intact, in
      frame fusion of TPR exon 15 and ALK exon 20 (t(1;2)(q31.1;p23)). The TPR-ALK
      fusion encodes a predicted protein of 1192 amino acids with a coiled-coil domain
      encoded by the 5'-2 of the TPR and juxtamembrane and kinase domains encoded by
      the 3'-end of the ALK. CONCLUSIONS: The novel fusion gene and its protein TRP
      ALK, harboring coiled-coil and kinase domains, could possess transforming
      potential and responses to treatment with ALK inhibitors. This case is the first
      report of TPR-ALK fusion transcript in clinical tumor samples and could provide a
      novel diagnostic and therapeutic candidate target for patients with cancer,
      including non-small-cell lung carcinoma.

PMID- 24736083
TI  - Characterization of fibroblast growth factor receptor 1 in small-cell lung
      cancer.
AB  - INTRODUCTION: There remains a significant therapeutic need for small-cell lung
      cancer (SCLC). We and others have reported high frequency of copy number gains in
      cytogenetic bands encoding fibroblast growth factor receptor 1 (FGFR1) in SCLC
      tumors and cell lines. METHODS: Thirteen SCLC cell lines and 68 SCLC patient
      tumor samples were studied for FGFR1 amplification. Growth inhibition assays were
      performed using PD173074, a pan-FGFR inhibitor to determine the correlation
      between FGFR1 expression and drug sensitivity. RESULTS: We did not detect FGFR1
      mutations in SCLC cell lines. Focal amplification of FGFR1 gene was found in five
      tumor samples (7%), with high-level focal amplification in only one tumor sample
      (1%). Amplification owing to polysomy of chromosome 8, where FGFR1 locates, was
      observed in 22 tumor samples (32%). There was no correlation between FGFR1 gene
      copy number and messenger RNA expression or protein expression in SCLC cells.
      FGFR inhibitor sensitivity correlated with FGFR1 copy number determined by real
      time polymerase chain reaction assay (r= -0.79; p = 0.01). CONCLUSION: FGFR1 gene
      mutations and focal amplification are rare in SCLC, but polysomy of chromosome 8
      is relatively common. FGFR1 copy number gain predicts sensitivity to FGFR
      inhibition, and FGFR expression correlates inversely with chemosensitivity.

PMID- 24736084
TI  - Management of mediastinal relapse after treatment with stereotactic body
      radiotherapy or accelerated hypofractionated radiotherapy for stage I/II non
      small-cell lung cancer.
AB  - PURPOSE/OBJECTIVE(S): Regional failures occur in up to 15% of patients treated
      with stereotactic body radiotherapy (SBRT) for stage I/II lung cancer. This
      report focuses on the management of the unique scenario of isolated regional
      failures. METHODS: Patients treated initially with SBRT or accelerated
      hypofractionated radiotherapy were screened for curative intent treatment of
      isolated mediastinal failures (IMFs). Local control, regional control,
      progression-free survival, and distant control were estimated from the date of
      salvage treatment using the Kaplan-Meier method. RESULTS: Among 160 patients
      treated from 2002 to 2012, 12 suffered IMF and were amenable to salvage
      treatment. The median interval between treatments was 16 months (2-57 mo). Median
      salvage dose was 66 Gy (60-70 Gy). With a median follow-up of 10 months, the
      median overall survival was 15 months (95% confidence interval, 5.8-37 mo). When
      estimated from original treatment, the median overall survival was 38 months (95%
      confidence interval, 17-71 mo). No subsequent regional failures occurred. Distant
      failure was the predominant mode of relapse following salvage for IMF with a 2
      year distant control rate of 38%. At the time of this analysis, three patients
      have died without recurrence while four are alive and no evidence of disease.
      High-grade toxicity was uncommon. CONCLUSIONS: To our knowledge, this is first
      analysis of salvage mediastinal radiation after SBRT or accelerated
      hypofractionated radiotherapy in lung cancer. Outcomes appear similar to stage
      III disease at presentation. Distant failures were common, suggesting a role for
      concurrent or sequential chemotherapy. A standard full course of external beam
      radiotherapy is advisable in this unique clinical scenario.

PMID- 24736085
TI  - A randomized, placebo-controlled, multicenter, biomarker-selected, phase 2 study
      of apricoxib in combination with erlotinib in patients with advanced non-small
      cell lung cancer.
AB  - Cyclooxygenase-2 (COX-2) overexpression is associated with a poor prognosis in
      non-small-cell lung cancer (NSCLC) and may promote resistance to epidermal growth
      factor receptor inhibitors. This randomized phase 2 trial evaluated apricoxib, a
      novel COX-2 inhibitor, in combination with erlotinib in biomarker-selected
      patients. Patients with stage IIIB/IV NSCLC previously treated with platinum
      based chemotherapy were randomized (2:1) to 400 mg/day apricoxib plus 150 mg/day
      erlotinib (AP/E) or placebo plus erlotinib (P/E) in 21-day cycles until disease
      progression or unacceptable toxicity. The primary endpoint was time to
      progression (TTP). A decrease of 50% or more from baseline urinary prostaglandin
      E2 metabolite after a 5-day, open-label, run-in period was used to select
      eligible patients. One hundred twenty patients (median age 64 years) were
      randomized (78 to AP/E and 42 to P/E). Overall median TTP was 1.8 months in the
      AP/E group and 2.1 months in the P/E group, with a 12% objective response rate in
      both groups (intent-to-treat analysis). A subgroup analysis in patients aged 65
      years or younger demonstrated a statistically significant TTP benefit for AP/E
      (hazard ratio 0.5 [95% confidence interval: not applicable-0.9]; p=0.018) and
      overall survival advantage at minimum 1-year follow-up (median 12.2 versus 4.0
      months; hazard ratio=0.5; p=0.021). The most common adverse events were rash,
      diarrhea, fatigue, and nausea. Toxicity contributed to early discontinuations in
      patients aged more than 65 years treated with AP/E. This is the first randomized
      placebo-controlled study of a COX-2 inhibitor in NSCLC to use a prospective
      patient-selection strategy. Although AP/E seemed to improve TTP and overall
      survival in a subset of patients aged 65 years or younger, the primary endpoint
      of the trial was not met. 

PMID- 24736086
TI  - Pseudoprogression after stereotactic body radiotherapy.

PMID- 24736087
TI  - Lung carcinomas with EGFR exon 19 insertions are sensitive to gefitinib
      treatment.

PMID- 24736088
TI  - Anger with murderous impulse induced by lamotrigine.
AB  - OBJECTIVE: To report two cases of major depressive disorder in which lamotrigine
      (LTG) induced anger with murderous impulse. PATIENTS: Case 1 was a 22-year-old
      man with symptoms of obsessive-compulsive disorder who developed major depressive
      disorder with antidepressant-induced hypomanic episodes. Case 2 was a 23-year-old
      woman experiencing an antidepressant-refractory depressive episode for whom
      remission was achieved by switching to a mood stabilizer and antipsychotics. In
      both cases LTG was started to treat the depressive episode. RESULTS: Case 1
      manifested with anger and murderous impulse when taking 125 mg/day of LTG. A
      reduction to 75 mg/day calmed this anger. Case 2 manifested with the same symptom
      when taking 25 mg/day of LTG, and the symptom immediately disappeared upon
      stopping LTG. CONCLUSIONS: Use of LTG for epilepsy in intellectually disabled
      patients was reported to be associated with onset or exacerbation of aggressive
      or violent behavior. The two cases would suggest that LTG may cause anger so
      severe as to be accompanied with murderous impulse when administered to patients
      with mood disorders. Physicians should be cognizant of this possible, albeit
      infrequent, adverse effect even in use of LTG for mood disorders.

PMID- 24736089
TI  - Biogas production from lignocelluloses by N-methylmorpholine-N-oxide (NMMO)
      pretreatment: effects of recovery and reuse of NMMO.
AB  - The effects of N-methylmorpholine-N-oxide (NMMO) pretreatment on barley straw and
      forest residues were investigated for biogas production. The pretreatments were
      performed at 90 degrees C with 85% NMMO for 3-30h. The best pretreatment
      conditions resulted in 100% improvement in methane yield during the subsequent
      digestion compared to that of the untreated lignocelluloses. Methane yields of
      0.23 and 0.15Nm(3) CH4/kg VS were obtained from barley straw and forest residues,
      respectively, corresponding to 88% and 83% of the theoretical yields. In
      addition, the effects of the pretreatment with recovered and reused NMMO was also
      studied over the course of five cycles. Pretreatment with recycled NMMO showed
      the same performance as the fresh NMMO on barley straw. However, pretreatment of
      forest residues with recycled NMMO resulted in 55% reduction in methane yield. 

PMID- 24736090
TI  - Cultivation of Monoraphidium sp., Chlorella sp. and Scenedesmus sp. algae in
      Batch culture using Nile tilapia effluent.
AB  - Monoraphidium sp., Chlorella sp. and Scenedesmus sp. algae were cultured in three
      volumes of Tilapia Effluent Medium (TEM) in comparison with the Bold Basal Medium
      (BBM) (Nichols and Bold, 1965). Specific growth rate (MU'), biomass dry
      productivity (Q), volumetric productivity (Qv) as well as lipid and protein
      content were measured. Then, volumetric productivities for both lipids and
      proteins were calculated (QVL and QVP). In Scenedesmus sp., BBM produced higher
      MU' and Qv than TEM in 1.5L volume. Chlorella sp. showed a higher QVL for BBM
      than TEM. Any observed difference in protein or lipid productivities among
      volumes was in favor of a greater productivity for 1.5L volume. Even when TEM had
      a larger protein content in Chlorella sp. than BBM, QVP was not different.
      Current results imply that TEM can be used as an alternative growth medium for
      algae when using Batch cultures, yet productivity is reduced. 

PMID- 24736091
TI  - Lipid droplet biogenesis.
AB  - Lipid droplets (LDs) are found in most cells, where they play central roles in
      energy and membrane lipid metabolism. The de novo biogenesis of LDs is a
      fascinating, yet poorly understood process involving the formation of a monolayer
      bound organelle from a bilayer membrane. Additionally, large LDs can form either
      by growth of existing LDs or by the combination of smaller LDs through several
      distinct mechanisms. Here, we review recent insights into the molecular process
      governing LD biogenesis and highlight areas of incomplete knowledge. 

PMID- 24736093
TI  - Reasons for non-attendance to cervical screening and preferences for HPV self
      sampling in Dutch women.
AB  - OBJECTIVES: High attendance rates in cervical screening are essential for
      effective cancer prevention. Offering HPV self-sampling to non-responders
      increases participation rates. The objectives of this study were to determine why
      non-responders do not attend regular screening, and why they do or do not
      participate when offered a self-sampling device. METHODS: A questionnaire study
      was conducted in the Netherlands from October 2011 to December 2012. A total of
      35,477 non-responders were invited to participate in an HPV self-sampling study;
      5347 women did opt out. Finally, 30,130 women received a questionnaire and self
      sampling device. RESULTS: The analysis was based on 9484 returned questionnaires
      (31.5%) with a self-sample specimen, and 682 (2.3%) without. Among women who
      returned both, the main reason for non-attendance to cervical screening was that
      they forgot to schedule an appointment (3068; 32.3%). The most important reason
      to use the self-sampling device was the opportunity to take a sample in their own
      time-setting (4763; 50.2%). A total of 30.9% of the women who did not use the
      self-sampling device preferred after all to have a cervical smear taken instead.
      CONCLUSIONS: Organisational barriers are the main reason for non-attendance in
      regular cervical screening. Important reasons for non-responders to the regular
      screening to use a self-sampling device are convenience and self-control.

PMID- 24736092
TI  - Using appropriate body mass index cut points for overweight and obesity among
      Asian Americans.
AB  - OBJECTIVE: Asian Americans have low prevalence of overweight/obesity based on
      standard BMI cut points yet have higher rates of diabetes. We examined the
      prevalence of overweight/obesity, using lower BMI cut points recommended by the
      World Health Organization (WHO) for Asians, and diabetes in Asian American
      subgroups in California. METHOD: Secondary analysis of the 2009 adult California
      Health Interview Survey (n=45,946) of non-Hispanic Whites (NHW), African
      Americans, Hispanics and Asians (Vietnamese, Chinese, Korean, Filipino, South
      Asian and Japanese). WHO Asian BMI cut points (overweight=23-27.5kg/m(2);
      obese>=27.5kg/m(2)) were used for Asian subgroups. Standard BMI cut points
      (overweight=25-29.9kg/m(2); obese>=30kg/m(2)) were applied for other groups.
      RESULTS: Among Asian subgroups, overweight/obesity was highest among Filipinos
      (78.6%), which was higher than NHWs (p<0.001) but similar to African Americans
      and Hispanics. Compared to NHW, diabetes prevalence was higher for Vietnamese,
      Koreans, Filipinos and South Asians with BMI=23-24.9kg/m(2) and Koreans,
      Filipinos and Japanese with BMI=27.5-29.9kg/m(2), the ranges WHO recommends as
      overweight or obese for Asians but not for other groups. CONCLUSIONS: Filipinos
      should be a priority population for overweight/obesity screening. Filipinos,
      Vietnamese, Korean, South Asians and Japanese have higher diabetes prevalence at
      lower BMI cut points. WHO Asian BMI cut points may have clinical utility to
      identify at-risk Asian Americans.

PMID- 24736095
TI  - (210)Pb as a tracer of soil erosion, sediment source area identification and
      particle transport in the terrestrial environment.
AB  - Although (137)Cs has been used extensively to study soil erosion and particle
      transport in the terrestrial environment, there has been much less work using
      excess or unsupported (210)Pb ((210)Pbxs) to study the same processes.
      Furthermore, since (137)Cs activities in soils are decreasing because of
      radioactive decay, some locations have an added complication due to the addition
      of Chernobyl-derived (137)Cs, and the activities of (137)Cs in the southern
      hemisphere are low, there is a need to develop techniques that use (210)Pbxs to
      provide estimates of rates of soil erosion and particle transport. This paper
      reviews the current status of (210)Pbxs methods to quantify soil erosion rates,
      to identify and partition suspended sediment source areas, and to determine the
      transport rates of particles in the terrestrial landscape. Soil erosion rates
      determined using (210)Pbxs are based on the unsupported (210)Pb ((210)Pbxs)
      inventory in the soil, the depth distribution of (210)Pbxs, and a mass balance
      calibration ('conversion model') that relates the soil inventory to the erosion
      rate using a 'reference site' at which neither soil erosion nor soil deposition
      has occurred. In this paper several different models are presented to illustrate
      the effects of different model assumptions such as the timing, depth and rates of
      the surface soil mixing on the calculated erosion rates. The suitability of model
      assumptions, including estimates of the depositional flux of (210)Pbxs to the
      soil surface and the post-depositional mobility of (210)Pb are also discussed.
      (210)Pb can be used as one tracer to permit sediment source area identification.
      This sediment 'fingerprinting' has been extended far beyond using (210)Pb as a
      single radioisotope to include numerous radioactive and stable tracers and has
      been applied to identifying the source areas of suspended sediment based on
      underlying rock type, land use (roads, stream banks, channel beds, cultivated or
      uncultivated lands, pasture lands, forested lands, construction sites,
      undisturbed lands) or style of erosion (sheet wash, rills, bank). The transport
      time of particles in the terrestrial system can be estimated using
      (7)Be/(210)Pbxs radionuclide ratios and from mass balance models of (210)Pbxs
      and/or (7)Be in streams. Watershed residence times can be calculated from the
      radionuclide inventory and the erosional loss rate. 

PMID- 24736094
TI  - Theory-based behavioral intervention increases self-reported physical activity in
      South African men: a cluster-randomized controlled trial.
AB  - OBJECTIVE: To determine whether a health-promotion intervention increases South
      African men's adherence to physical-activity guidelines. METHOD: We utilized a
      cluster-randomized controlled trial design. Eligible clusters, residential
      neighborhoods near East London, South Africa, were matched in pairs. Within
      randomly selected pairs, neighborhoods were randomized to theory-based,
      culturally congruent health-promotion intervention encouraging physical activity
      or attention-matched HIV/STI risk-reduction control intervention. Men residing in
      the neighborhoods and reporting coitus in the previous 3 months were eligible.
      Primary outcome was self-reported individual-level adherence to physical-activity
      guidelines averaged over 6-month and 12-month post-intervention assessments. Data
      were collected in 2007-2010. Data collectors, but not facilitators or
      participants, were blind to group assignment. RESULTS: Primary outcome intention
      to-treat analysis included 22 of 22 clusters and 537 of 572 men in the health
      promotion intervention and 22 of 22 clusters and 569 of 609 men in the attention
      control intervention. Model-estimated probability of meeting physical-activity
      guidelines was 51.0% in the health-promotion intervention and 44.7% in attention
      matched control (OR=1.34; 95% CI, 1.09-1.63), adjusting for baseline prevalence
      and clustering from 44 neighborhoods. CONCLUSION: A theory-based culturally
      congruent intervention increased South African men's self-reported physical
      activity, a key contributor to deaths from non-communicable diseases in South
      Africa. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01490359.

PMID- 24736096
TI  - Comparison of EUCAST and CLSI broth microdilution methods for the susceptibility
      testing of 10 systemically active antifungal agents when tested against Candida
      spp.
AB  - The antifungal broth microdilution (BMD) method of the European Committee on
      Antimicrobial Susceptibility Testing (EUCAST) was compared with Clinical and
      Laboratory Standards Institute (CLSI) BMD method M27-A3 for amphotericin B,
      flucytosine, anidulafungin, caspofungin, micafungin, fluconazole, isavuconazole,
      itraconazole, posaconazole, and voriconazole susceptibility testing of 357
      isolates of Candida. The isolates were selected from global surveillance
      collections to represent both wild-type (WT) and non-WT MIC results for the
      azoles (12% of fluconazole and voriconazole results were non-WT) and the
      echinocandins (6% of anidulafungin and micafungin results were non-WT). The study
      collection included 114 isolates of Candida albicans, 73 of C. glabrata, 76 of C.
      parapsilosis, 60 of C. tropicalis, and 34 of C. krusei. The overall essential
      agreement (EA) between EUCAST and CLSI results ranged from 78.9% (posaconazole)
      to 99.6% (flucytosine). The categorical agreement (CA) between methods and
      species of Candida was assessed using previously determined CLSI epidemiological
      cutoff values. The overall CA between methods was 95.0% with 2.5% very major (VM)
      and major (M) discrepancies. The CA was >93% for all antifungal agents with the
      exception of caspofungin (84.6%), where 10% of the results were categorized as
      non-WT by the EUCAST method and WT by the CLSI method. Problem areas with low EA
      or CA include testing of amphotericin B, anidulafungin, and isavuconazole against
      C. glabrata, itraconazole, and posaconazole against most species, and caspofungin
      against C. parapsilosis, C. tropicalis, and C. krusei. We confirm high level EA
      and CA (>90%) between the 2 methods for testing fluconazole, voriconazole, and
      micafungin against all 5 species. The results indicate that the EUCAST and CLSI
      methods produce comparable results for testing the systemically active antifungal
      agents against the 5 most common species of Candida; however, there are several
      areas where additional steps toward harmonization are warranted. 

PMID- 24736097
TI  - Environmental public health dimensions of shale and tight gas development.
AB  - BACKGROUND: The United States has experienced a boom in natural gas production
      due to recent technological innovations that have enabled this resource to be
      produced from shale formations. OBJECTIVES: We reviewed the body of evidence
      related to exposure pathways in order to evaluate the potential environmental
      public health impacts of shale gas development. We highlight what is currently
      known and identify data gaps and research limitations by addressing matters of
      toxicity, exposure pathways, air quality, and water quality. DISCUSSION: There is
      evidence of potential environmental public health risks associated with shale gas
      development. Several studies suggest that shale gas development contributes to
      ambient air concentrations of pollutants known to be associated with increased
      risk of morbidity and mortality. Similarly, an increasing body of studies suggest
      that water contamination risks exist through a variety of environmental pathways,
      most notably during wastewater transport and disposal, and via poor zonal
      isolation of gases and fluids due to structural integrity impairment of cement in
      gas wells. CONCLUSION: Despite a growing body of evidence, data gaps persist.
      Most important, there is a need for more epidemiological studies to assess
      associations between risk factors, such as air and water pollution, and health
      outcomes among populations living in close proximity to shale gas operations.

PMID- 24736098
TI  - Differential effects of chemoattractants on mast cell recruitment in vivo.
AB  - Rats were injected with rat recombinant (rr) IL3, rrSCF, rrIL-3+rrSCF, rrRANTES
      and LTB4. Six hours after subcutaneous injection of rrIL-3 or rrIL-3+rrSCF, there
      was an increase in mast cell numbers in the skin and spleen. Peritoneal mast
      cells were recruited following i.p. injection of rrIL-3, but with rrIL-3+rrSCF
      recruitment was delayed. Immunostaining with a mast cell specific antibody showed
      that immature orthochromatic mast cells were being recruited. rrIL-3 induced
      recruitment of mast cells to the peritoneal cavity was blocked by anti-integrin
      antibodies. Mast cell recruitment depended on the target tissue and the time of
      exposure to the chemoattractant. 

PMID- 24736099
TI  - Reliability and validity of expert assessment based on airborne and urinary
      measures of nickel and chromium exposure in the electroplating industry.
AB  - The reliability and validity of six experts' exposure ratings were evaluated for
      64 nickel-exposed and 72 chromium-exposed workers from six Shanghai
      electroplating plants based on airborne and urinary nickel and chromium
      measurements. Three industrial hygienists and three occupational physicians
      independently ranked the exposure intensity of each metal on an ordinal scale (1
      4) for each worker's job in two rounds: the first round was based on responses to
      an occupational history questionnaire and the second round also included
      responses to an electroplating industry-specific questionnaire. The Spearman
      correlation (r(s)) was used to compare each rating's validity to its
      corresponding subject-specific arithmetic mean of four airborne or four urinary
      measurements. Reliability was moderately high (weighted kappa range=0.60-0.64).
      Validity was poor to moderate (r(s)=-0.37-0.46) for both airborne and urinary
      concentrations of both metals. For airborne nickel concentrations, validity
      differed by plant. For dichotomized metrics, sensitivity and specificity were
      higher based on urinary measurements (47-78%) than airborne measurements (16
      50%). Few patterns were observed by metal, assessment round, or expert type.
      These results suggest that, for electroplating exposures, experts can achieve
      moderately high agreement and (reasonably) distinguish between low and high
      exposures when reviewing responses to in-depth questionnaires used in population
      based case-control studies.

PMID- 24736101
TI  - Respiratory and sensory irritation symptoms among residents exposed to low-to
      moderate air pollution from biodegradable wastes.
AB  - Previous studies have reported increased occurrence of respiratory and sensory
      irritation symptoms among residents living close to biodegradable waste sites.
      However, few studies have been able to quantify direct and annoyance-mediated
      effects based on individual-specific assessments of chemical exposures. We
      examined associations between residential exposures to a proxy gas (ammonia, NH3)
      from biodegradable wastes (mainly from farming, animal and agricultural
      activities) and odor annoyance and six respiratory and sensory irritation
      symptoms (self-reported), using adjusted logistic regression models and mediation
      analyses. Individual-specific NH3 exposures (n=454) in residential environments
      during 2005-2010 were calculated by the Danish Eulerian long-range transport
      model and the local-scale transport deposition model. Residential NH3 exposure
      was associated with increased frequency of four symptoms, including "eyes
      itching, dryness or irritation" and "cough" (ORadj=1.69; 95% CI: 1.09-2.61 and
      ORadj=1.75; 95% CI: 1.12-2.74, for each unit increase in loge(NH3 exposure)).
      Odor annoyance mediated the effect of exposure on cough and three sensory
      irritation symptoms. Mediation was either full (indirect-only effects) or partial
      (direct and indirect effects). This study provides support for the existence of
      indirect associations between residential exposures to low-to-moderate air
      pollution from wastes and symptoms, as well as direct dose-response associations
      for some of the symptoms. 

PMID- 24736100
TI  - Reproducibility of urinary bisphenol A concentrations measured during pregnancy
      in the Generation R Study.
AB  - The potential human health effects of bisphenol A (BPA) exposure are a public
      health concern. In order to design adequately powered epidemiological studies to
      address potential health effects, data on the reproducibility of BPA
      concentration in serial urine specimens taken during pregnancy are needed. To
      provide additional data on the reproducibility of maternal urine specimens, 80
      women in the Generation R Study (Rotterdam, The Netherlands) contributed a spot
      urine specimen at <18, 18-25, and >25 weeks of pregnancy. Reproducibility,
      estimated by the intraclass correlation coefficient (ICC), was 0.32 (95%
      confidence interval: 0.18-0.46), and, on a creatinine basis, 0.31 (95% confidence
      interval: 0.16-0.47). Although the ICC observed in the Generation R Study is
      slightly higher than previous reproducibility studies of BPA, it nevertheless
      indicates a high degree of within-person variability that presents challenges for
      designing well-powered epidemiologic studies. 

PMID- 24736102
TI  - Mutation spectrum of hepatocellular carcinoma from eastern-European patients
      betrays the impact of a complex exposome.
AB  - Genomic analysis of hepatocellular carcinoma (HCC) has been shown to provide
      clues about local risk factors. In the last decades, the mortality from malignant
      liver tumors increased sharply in Romania, where both hepatitis viruses and
      environmental pollutants are known to be highly prevalent. To date, HCC from this
      country has not been subject to molecular characterization. We analyzed a series
      of 48 consecutive HCC cases. Point mutations were searched in 9 nuclear genes and
      the mitochondrial D-loop. Oxidative stress response was monitored through
      measurement of gene expression (NRF2, KEAP1, SRXN1, and CES1) by qRT-PCR. An
      atypical mutation spectrum was observed, as more than 40% of DNA changes were
      oxidative stress-associated T>C or T>G lesions (T>S). These mutations affected
      primarily genes encoding for beta-catenin and NRF2 (P<0.0001). Besides, tumors
      from patients born in Greater Bucharest carried TP53 mutations more frequently
      than others (45 vs 10%, P=0.02). Finally, a R249S mutation of TP53, well-known
      hallmark of aflatoxin B1 exposure, was found. Our findings indicate, therefore,
      that distinct mutagenic processes affect Romanian patients with HCC. Further
      analyses are now warranted in order to identify causal lifestyle or environmental
      factors. 

PMID- 24736103
TI  - Waterpipe cafes in Baltimore, Maryland: Carbon monoxide, particulate matter, and
      nicotine exposure.
AB  - Waterpipe smoking has been growing in popularity in the United States and
      worldwide. Most tobacco control regulations remain limited to cigarettes. Few
      studies have investigated waterpipe tobacco smoke exposures in a real world
      setting. We measured carbon monoxide (CO), particulate matter (PM)2.5, and
      airborne nicotine concentrations in seven waterpipe cafes in the greater
      Baltimore area. Area air samples were collected between two and five hours, with
      an average sampling duration of three hours. Waterpipe smoking behaviors were
      observed at each venue. Indoor air samplers for CO, PM2.5, and airborne nicotine
      were placed in the main seating area 1-2 m above the floor. Indoor airborne
      concentrations of PM2.5 and CO were markedly elevated in waterpipe cafes and
      exceeded concentrations that were observed in cigarette smoking bars. Air
      nicotine concentrations, although not as high as in venues that allow cigarette
      smoking, were markedly higher than in smoke-free bars and restaurants.
      Concentrations of PM approached occupational exposure limits and CO exceeded
      occupational exposure guidelines suggesting that worker protection measures need
      to be considered. This study adds to the literature indicating that both
      employees and patrons of waterpipe venues are at increased risk from complex
      exposures to secondhand waterpipe smoke. 

PMID- 24736104
TI  - Synthesis, In Vitro and In Vivo Evaluation of the N-ethoxycarbonylmorpholine
      Ester of Diclofenac as a Prodrug.
AB  - The N-ethoxycarbonylmorpholine moiety was evaluated as a novel prodrug moiety for
      carboxylic acid containing drugs represented by diclofenac (1). Compound 2, the N
      ethoxycarbonylmorpholine ester of diclofenac was synthesized and evaluated as a
      potential prodrug. The stability of the synthesized prodrug was evaluated in
      solutions of pH 1 and 7.4, and in plasma. The ester's half lives were found to be
      8 h, 47 h and 21 min in pH 1, pH 7.4 and plasma, respectively. Equimolar doses of
      diclofenac sodium and its synthesized prodrug were administered orally to a group
      of rabbits in a crossover study to evaluate their pharmacokinetic parameters. The
      prodrug 2 shows a similar rate and extent of absorption as the parent drug (1).
      The ulcerogenicity of the prepared prodrug was evaluated and compared with the
      parent drug. The prodrug showed less ulcerogenicity as detected by fewer number
      and smaller size of ulcers. In conclusion, the newly synthesized N
      ethoxycarbonylmorpholine ester of diclofenac prodrug showed appropriate stability
      properties at different pHs, similar pharmacokinetic profile, and much less
      ulcerogenecity at the GIT compared to the parent drug diclofenac. 

PMID- 24736105
TI  - Risk factors for the development of pulmonary oil embolism after transcatheter
      arterial chemoembolization of hepatic tumors.
AB  - Pulmonary oil embolism (POE) is a rare fatal complication after transcatheter
      arterial embolization (TAE) and transcatheter arterial chemoembolization (TACE).
      As risk factors have not been clearly delineated, the aim of the present study
      was to identify the risk factors for development of POE after TACE. A
      retrospective analysis was carried out on patients with unresectable
      hepatocellular carcinoma who received TAE or TACE at the Tri-Service General
      Hospital (Taiwan) between January 2005 and December 2008. The diagnosis of TAE
      induced or TACE-induced POE was based on development of respiratory signs and
      symptoms relatively soon after the procedure, as well as based on characteristic
      radiographic findings. Of the 219 enrolled patients in this study, 20 were
      diagnosed with POE after TAE or TACE. On univariate logistic regression analysis,
      patients developing POE were found to be older (67.95+/-15.95 vs. 61.44+/-12.59
      years, P=0.033), with a lower serum albumin level (3.25+/-0.58 vs. 3.62+/-0.57
      g/dl, P=0.009), a higher grade of liver cirrhosis as classified on the basis of
      Child's criteria (P<0.006), a larger tumor size (8.55+/-4.52 vs. 4.78+/-3.97 cm
      in diameter, P<0.001), a higher lipioidol dose (22.35+/-11.01 vs. 13.69+/-7.66
      ml, P=0.003), and a higher doxorubicin dose (50.27+/-7.05 vs. 40.75+/-13.61 mg,
      P<0.001). Following multivariate logistic regression analysis, only lipiodol dose
      was found to be a significant risk factor for POE (odds ratio=1.133, 95%
      confidence interval: 1.004, 1.279; P=0.044). The receiver operator characteristic
      curve cutoff point for lipiodol dose level was 14.5 ml, with a sensitivity of 80%
      and a specificity of 66.3%. In conclusion, the lipiodol dose could be considered
      as a predictive factor for POE after TAE or TACE in hepatic malignant tumor
      patients. On the basis of this retrospective study, the safe lipiodol dose to
      minimize the risk for POE is 14.5 ml or lower; however, larger, prospective
      studies are needed to determine the optimally safe and yet efficacious dose. 

PMID- 24736106
TI  - Nano-thrombelastography of fibrin during blood plasma clotting.
AB  - Hemostasis is a complex process that relies on the sensitive balance between the
      formation and breakdown of the thrombus, a three-dimensional polymer network of
      the fibrous protein fibrin. Neither the details of the fibrinogen-fibrin
      transition, nor the exact mechanisms of fibrin degradation are fully understood
      at the molecular level. In the present work we investigated the nanoscale-changes
      in the viscoelasticity of the 3D-fibrin network during fibrinogenesis and
      streptokinase (STK)-induced fibrinolysis by using a novel application of force
      spectroscopy, named nano-thrombelastography. In this method the changes in the
      bending of an oscillating atomic-force-microscope (AFM) cantilever in human blood
      plasma droplet were followed as a function of time. Whereas the global features
      of the time-dependent change in cantilever deflection corresponded well to a
      macroscopic thrombelastogram, the underlying force spectra revealed large, sample
      dependent oscillations in the range of 3-50nN and allowed the separation of
      elastic and viscous components of fibrin behavior. Upon STK treatment the nano
      thrombelastogram signal decayed gradually. The decay was driven by a decrease in
      thrombus elasticity, whereas thrombus viscosity decayed with a time delay. In
      scanning AFM images mature fibrin appeared as 17-nm-high and 12-196-nm-wide
      filaments. STK-treatment resulted in the decrease of filament height and the
      appearance of a surface roughness with 23.7nm discrete steps that corresponds
      well to the length of a fibrinogen monomer. Thus, the initial decay of thrombus
      elasticity during fibrinolysis may be caused by the axial rupture of fibrin
      fibers. 

PMID- 24736107
TI  - Carbon-doped SiO(x) nanowires with a large yield of white emission.
AB  - The growth of SiOx nanowires (NWs) with intense white emission is reported. Due
      to carbon monoxide gas being used as a dopant precursor, carbon-doped under
      stoichiometric silicon dioxide NWs are obtained. The doping of the NWs is studied
      by means of x-ray photoelectron spectroscopy, which allows to assess the presence
      of carbon atoms in the silicon oxide amorphous structure. The light emission
      properties are studied by means of cathodoluminescence spectroscopy, which shows
      three main emission bands set at 2.7 eV (blue), 2.3 eV (green) and 1.9 eV (red),
      resulting in the white emission.

PMID- 24736108
TI  - Second opinion reduces hysterectomies for uterine fibroids, study shows.

PMID- 24736109
TI  - Undiagnosed myasthenia gravis owing to a very unusual primary presentation.
AB  - Myasthenia gravis (MG) is an uncommon autoimmune disorder presenting with
      fluctuating, progressive muscle weakness. The typical initial presentation
      includes ocular symptoms of ptosis, diplopia, or both. In the literature, other
      late symptoms have been described. The inability to close the jaws or difficulty
      in closing the jaws is an uncommon symptom of muscle weakness. Studies have found
      that only 4% of patients with MG ever complain of, or demonstrate, masticatory
      muscular weakness with an inability to close the jaws or difficulty in closing
      the jaws. In the present case, although the patient may have manifested other
      symptoms, his primary complaint was the inability to masticate as a result of
      muscular weakness and the difficulty in closing the jaw. The symptoms had
      reportedly been present for several months. The case is interesting in that the
      patient presented with an uncommon symptom as the primary complaint. The
      patient's recall and communication of his medical history was poor, and it is
      unclear as to all the factors that may have delayed the diagnosis. However, it is
      important for dentists to recognize these atypical symptoms of MG so that they
      can either order the initial tests or make the appropriate referral.

PMID- 24736110
TI  - High-quality image acquisition by double exposure overlap in dental cone beam
      computed tomography.
AB  - OBJECTIVE: With a double exposure overlapping cone beam computed tomography
      (CBCT) scan technique, using CBCT acquisition radiation dose, the objective was
      to obtain apparent density similar to that of multidetector computed tomography
      (MDCT). STUDY DESIGN: Factory quality-assurance phantom and water phantom were
      used for the evaluation of apparent density fidelity of iCAT scans in different
      modes. Each scan's apparent density was analyzed for identical regions using
      ImageJ, version 1.42q. RESULTS: The iCAT Classic extended height acquisition with
      4-cm central overlap and reconstruction of 2 groups of 300 projections per
      rotation for the water and quality-assurance CBCT phantoms resulted in improved
      apparent density fidelity. This apparent density accuracy was superior to that of
      iCAT scan at high resolution (600 projections during 1 rotation). CONCLUSIONS:
      Using double exposure overlapping CBCT scans allows the analysis quality to be
      comparable with that of MDCT.

PMID- 24736111
TI  - Serum albumin correlates with affective prosody in adult males with attention
      deficit hyperactivity disorder.
AB  - The aim of this study was to determine the relationship between serum albumin,
      affective prosody, and symptoms of attention-deficit hyperactivity disorder
      (ADHD) found coincidentally in a recently published study. Here, serum albumin
      levels were assessed as a covariate. Twenty healthy male adults (controls) and 20
      adult male patients with ADHD participated in the study on two study days. Serum
      albumin levels and performance in an affective prosody task were assessed, and
      correlations were determined. Serum albumin had a significant correlation with
      performance on an affective prosody task on both of the 2 study days. The same
      correlations were not significant in the healthy control group. There was no
      difference in the serum albumin level between patients with ADHD and healthy
      controls. The association between serum albumin and affective prosody in adults
      with ADHD is a novel finding. However, to date, there is no clear theory that
      explains this association. Future research should analyze whether serum albumin
      influences causes changes in performance in affective prosody using experimental
      designs. 

PMID- 24736112
TI  - Post-acute crisis text messaging outreach for suicide prevention: a pilot study.
AB  - Several post-suicide prevention strategies such as sending postcards or making
      phone calls have been used to keep in contact with suicide attempters. The
      continuity of care has been beneficial to the prevention of post-acute suicidal
      behaviors. The aim of the study was to evaluate the technical feasibility and
      acceptability of text messaging outreach in post-acute suicide attempters.
      Eighteen post-suicidal patients were included in a prospective, monocentric, open
      label, 2 months pilot study. The text messages were sent from the intranet
      program that we specially developed for the study. Technical feasibility of this
      text message intervention was evaluated by the analysis of text message reports.
      Acceptability of such intervention was evaluated by a standardized phone
      interview. Our study showed that receiving text messages sent from an intranet
      program after a suicide attempt is technically possible. This post-crisis
      outreach program was accepted by the patients who found it to have a positive
      preventive impact. Text messaging outreach offers several advantages such as
      lower cost, and easier utilization compared to current post-acute care
      strategies. We suggest further randomized controlled trials in a large sample of
      suicidal patients to assess the efficacy of this novel outreach tool for
      prevention of post-acute suicide. 

PMID- 24736113
TI  - Syntheses of stable, synthetic diadenosine polyphosphate analogues using
      recombinant histidine-tagged lysyl tRNA synthetase (LysU).
AB  - Recombinant Escherichia coli lysyl-tRNA synthase (LysU) has been previously
      utilised in the production of stabile, synthetic diadenosine polyphosphate (ApnA)
      analogues. Here we report on the extended use of a new recombinant histidine
      residue-tagged LysU as a tool for highly controlled phosphatephosphate bond
      formation between nucleotides, avoiding the need for complex protecting group
      chemistries. Resulting high yielding tandem LysU-based biosynthetic
      synthetic/synthetic-biosynthetic strategies emerge for the preparation of
      varieties of ApnA analogues directly from inexpensive natural nucleotides and
      nucleosides. Analogues so formed make a useful small library with which to probe
      ApnA activities in vitro and in vivo leading to the discovery of new, potentially
      potent biopharmaceuticals active against chronic pain and other chronic, high
      burden disease states. 

PMID- 24736114
TI  - Synthesis and biological evaluation of cinnamido linked benzophenone hybrids as
      tubulin polymerization inhibitors and apoptosis inducing agents.
AB  - A new class of hybrid molecules containing cinnamide subunit linked to
      benzophenone as inhibitors of tubulin polymerization were synthesized and
      evaluated for their anticancer potential. These hybrids exhibit anticancer
      activity with IC50 values ranging from 0.06 to 16.3MUM. Compounds 4f and 4g
      possessing fluoro and trifluoromethyl on the cinnamido subunit showed significant
      cytotoxic activity with IC50 values 0.06 and 0.09MUM against HeLa cell line,
      respectively. These compounds showed cell cycle arrest at G2/M phase of the cell
      cycle and inhibited tubulin polymerization followed by activation of caspase-3
      activity and apoptotic cell death. Further in vitro tubulin polymerization assay
      showed that the level of tubulin inhibition was comparable to that of 2a for the
      compounds 4f and 4g. Moreover, Hoechst 33258 staining and DNA fragmentation assay
      suggested that these compounds induce cell death by apoptosis. Overall, the
      current study demonstrates that the synthesis of benzophenone linked cinnamide
      subunit conjugates as promising anticancer agents with G2/M arrest and apoptotic
      inducing ability via targeting tubulin. 

PMID- 24736115
TI  - SPION-Smac mimetic nano-conjugates: putative pro-apoptotic agents in oncology.
AB  - Non-covalent (NP-1/3) and covalent (NP-A-1/3) pro-apoptotic SPION-Smac mimetic
      nano-conjugates antitumor agents are reported. The solution synthesis of key Smac
      mimetics, their support onto SPIONs through non-covalent adsorption (NP-1/3) or
      APTES-mediated covalent binding (NP-A-1/3), the analytical characterization of
      SPION-Smac mimetic conjugates, their target affinity in cell-free assays, and
      their cytotoxicity against tumor cells are thoroughly described. 

PMID- 24736116
TI  - Identification of novel IP receptor agonists using historical ligand biased
      chemical arrays.
AB  - By considering published structural information we have designed high throughput
      biaryl lipophilic acid arrays leveraging facile chemistry to expedite their
      synthesis. We rapidly identified multiple hits which were of suitable IP agonist
      potency. These relatively simple and strategically undecorated molecules present
      an ideal opportunity for optimization towards our target candidate profile. 

PMID- 24736117
TI  - Elucidation of different inhibition mechanism of small chemicals on PtdInsP
      binding domains using in silico docking experiments.
AB  - Phosphatidylinositides, most negatively charged lipids in cellular membranes,
      regulate diverse effector proteins through the interaction with their lipid
      binding domains. We have previously reported inhibitory effect of small chemicals
      on the interaction between PtdIns(3,4,5)P3 and Btk PH domain. Here, we report
      that the inhibitory effects of same sets of chemicals on Grp1 PH domain and
      epsin1 ENTH domain to elucidate diversity of inhibitory mechanisms upon different
      lipid binding domains. Among the chemicals, chemical 8 showed best inhibition in
      vitro assay for Grp1 PH domain and epsin1 ENTH domain, and then the interaction
      between small chemicals and lipid binding domains was further investigated by in
      silico docking experiments. As a result, it was concluded that the diverse
      inhibitory effects on different lipid binding domains were dependent on not only
      the number of interactions between small chemical and domain, but also additional
      interaction with positively charged surfaces as the secondary binding sites. This
      finding will help to develop lipid binding inhibitors as antagonists for lipid
      protein interactions, and these inhibitors would be novel therapeutic drug
      candidates via regulating effector proteins involved in severe human diseases. 

PMID- 24736118
TI  - Synthesis and biological activities of 2,3-dihydro-1,3,4-oxadiazole compounds and
      its derivatives as potential activator of ryanodine receptors.
AB  - A series of novel 2,3-dihydro-1,3,4-oxadiazoles containing N-pyridylpyrazole
      carboxamides moieties were obtained by applying a new synthetic route. Their
      insecticidal tests against oriental armyworm (Mythimna separata) and diamondback
      moth (Plutella xylostella) indicated that most of the compounds showed moderate
      to excellent activities at the testing concentrations. In particular, compound 6a
      showed 40% larvicidal activities against oriental armyworm at 1mg/L, while 7a
      against diamondback was 100% at 0.01mg/L. Calcium imaging results demonstrated
      that 6a, 6d and 7a stimulated a transient elevation in [Ca(2+)]i in the absence
      of external calcium after the central neurons dye loading with fluo-3 AM,
      implying that these novel compounds were potential activators of the ligand-gated
      calcium channel on the endoplasmic reticulum. 

PMID- 24736119
TI  - Protracted symptoms in lymphocytic choriomeningitis: a case report.
AB  - Assumed to be underreported and underrecognized, lymphocytic choriomeningitis
      presents as a febrile illness transmitted by the common house mouse, Mus
      musculus. Although asymptomatic or mild febrile illnesses are commonplace,
      meningitis and meningoencephalitis may develop after symptoms have seemed to
      improve. Neurologic sequelae are not typical but have been reported and can
      persist for months. We report a documented case of lymphocytic choriomeningitis
      in which a previously healthy 17-year-old girl experienced debilitating recurrent
      headaches and arthralgias for more than a year after discharge.
      Neuropsychological testing and visual changes were also documented. Further
      research is needed to estimate the prevalence of this infection, although it has
      been estimated that 5% of American adults have antibodies to lymphocytic
      choriomeningitis virus. Education and awareness of the medical community as well
      as the general public will be critical in prevention as well as advancing future
      treatment modalities of lymphocytic choriomeningitis virus. 

PMID- 24736120
TI  - Case report: cytokine and CD4+ T-cell profiles of monozygotic twins with autism
      and divergent comorbidities and drug treatment.
AB  - Autism spectrum disorders are neurodevelopmental disorders that are thought to be
      caused by a gene-by-environment interaction and in which various immune
      alterations are reported. We investigate CD4(+) T-cell cytokine profiles and
      subpopulations in 19-year-old monozygotic twins with autism and different
      comorbidities. CD4(+) T cells from the twin with epilepsy produce more interferon
      gamma, less interleukin-17, and have an increased interferon-gamma/interleukin-4
      ratio. CD4(+) T cells from the twin with multiple sclerosis exhibit a cytokine
      profile similar to an age and gender-matched control and a higher percentage of T
      regulatory (Treg) cells. The twins' mother's T cells produce very high levels of
      both interleukin-17 and interferon-gamma. Cytokine and CD4(+) T-cell
      abnormalities in the twins could contribute to or be a result of the
      manifestation of their divergent comorbidities. A proinflammatory, autoimmune
      polarized cytokine profile is observed in this unique family with autism. 

PMID- 24736121
TI  - Evaluation of thyroid hormones in children receiving carbamazepine or valproate:
      a prospective study.
AB  - The aim of this study was to determine the alterations in thyroid function during
      carbamazepine or valproate monotherapy in a prospective study. Forty patients
      treated with valproate, 33 patients treated with carbamazepine, and 36 control
      patients, all aged between 2 and 18 years, were enrolled in our study. Serum
      levels of thyroid hormones were measured before the beginning of the
      antiepileptic therapy and at 6 and 12 months of treatment. Carbamazepine-treated
      patients showed mean serum thyroid hormone levels significantly lower than
      baseline evaluation and the control group. Thyroid-stimulating hormone levels at
      6 and 12 months were not significantly different in carbamazepine treated
      patients. Serum hormone levels did not change during valproate treatment. Thyroid
      stimulating hormone levels were significantly higher at the 12th month of
      valproate treatment. Our data suggest that although carbamazepine causes
      significant alterations in thyroid hormone levels, these changes do not lead to
      clinical symptoms at the follow-up period of 12 months. 

PMID- 24736122
TI  - Ruptured disc after arthroscopic repositioning in the temporomandibular joint: a
      retrospective magnetic resonance imaging study.
AB  - Our aim was to explore the incidence of rupture after arthroscopic repositioning
      of the disc of the temporomandibular joint (TMJ) by reviewing magnetic resonance
      images (MRI) of the TMJ taken before and after operation, and to investigate
      correlations retrospectively. We studied 247 patients with anterior disc
      displacement of the TMJ, and categorised them into 3 groups based on the
      postoperative MRI. The first group comprised those whose disc ruptured after
      repositioning, the second those who had a possible rupture of the disc after
      repositioning, and the third had no rupture of the disc after repositioning. Age,
      sex, duration of symptoms, maximum incisal mouth opening, whether the anterior
      disc displacement was unilateral or bilateral, and the Wilkes stage, were
      included in the analysis. The incidence of rupture (5/247) was 2%. Weak points at
      the intermediate zone of the disc were found in 4 of the 5 joints. The patients
      whose discs ruptured were significantly younger than the other 2 groups
      (p=0.001). There was no statistically significant difference in preoperative
      duration of symptoms and mouth opening among the groups. The proportions of
      unilateral and bilateral disc displacement (p=0.047) and Wilkes stage (p=0.027)
      differed among the 3 groups. The Wilkes stages was significantly more advanced in
      the ruptured group than in the other 2 groups (p=0.027) with 4/5 being bilateral.
      The weak point in the intermediate zone of the disc on MRI could be a sign of
      rupture. Teenagers and young adults with anterior disc displacement without
      reduction, particularly those in whom it is bilateral, are at a higher risk of a
      rupture after repositioning of the disc by arthroscopy. 

PMID- 24736123
TI  - Efficient anaerobic digestion of whole microalgae and lipid-extracted microalgae
      residues for methane energy production.
AB  - The primary aim of this study was to completely investigate extensive biological
      methane potential (BMP) on both whole microalgae and its lipid-extracted biomass
      residues with various degrees of biomass pretreatment. Specific methane
      productivities (SMP) under batch conditions for non-lipid extracted biomass were
      better than lipid-extracted biomass residues and exhibited no signs of ammonia or
      carbon/nitrogen (C/N) ratio inhibition when digested at high I/S ratio (I/S
      ratio?1.0). SMP for suitably extracted biomass ranged from 0.30 to 0.38LCH4/gVS
      (volatile solids). For both whole and lipid-extracted biomass, overall organic
      conversion ranged from 59.33 to 78.50 as a measure of %VS reduction with greater
      percentage biodegradability in general found within the lipid-extracted biomass.
      Higher production levels correlated to lipid content with a linear relationship
      between SMP and ash-free lipid content being developed at a R(2) of 0.814. 

PMID- 24736124
TI  - Hypolipidemic effect of the polysaccharides from Porphyra yezoensis.
AB  - This study was performed to investigate the hypolipidemic effect of the
      polysaccharides extracted from Porphyra yezoensis. Male Sprague-Dawley rats were
      divided into three groups and orally treated with diets containing either high
      fat, P. yezoensis polysaccharides (PPs), or normal fat. Treatment of male Sprague
      Dawley rats with PPs led not only to significant decreases in plasma
      triacylglycerol, total cholesterol, and plasma low-density lipoprotein
      cholesterol and an increase in plasma high-density lipoprotein cholesterol, but
      also to significant decreases in liver weight, triacylglycerol and cholesterol.
      Therefore, the results suggest that PPs had a high hypolipidemic activity and
      could be used as a potential therapeutic agent for hyperlipidemia. 

PMID- 24736125
TI  - Implementation of a novel point-of-care ultrasound billing and reimbursement
      program: fiscal impact.
AB  - OBJECTIVES: The aim of this study was to determine the fiscal impact of
      implementation of a novel emergency department (ED) point-of-care (POC)
      ultrasound billing and reimbursement program. METHODS: This was a single-center
      retrospective study at an academic medical center. A novel POC ultrasound billing
      protocol was implemented using the Q-path Web-based image archival system.
      Patient care ultrasound examination reports were completed and signed
      electronically online by faculty using Q-path. A notification was automatically
      sent to ED coders from Q-path to bill the scans. ED coders billed the
      professional fees for scans on a daily basis and also notified hospital coders to
      bill for facility fees. A fiscal analysis was performed at the end of the year
      after implementing the new billing protocol, and a before-and-after comparison
      was conducted. RESULTS: After implementation of the new billing program, there
      was a 45% increase in the ED faculty participation in billing for patient care
      examinations (30%-75%). The number of ultrasound examinations billed increased
      5.1-fold (4449 vs 857) during the post implementation period. The total units
      billed increased from previous year for professional services to 4157 from 649
      and facility services to 3266 from 516. During the post implementation period,
      the facility fees revenue increased 7-fold and professional fees revenue
      increased 6.34-fold. After deducting the capital costs and ongoing operational
      costs from approximate collections, the net profits gained by our ED ultrasound
      program was approximately $350000. CONCLUSIONS: Within 1 year of inception, our
      novel POC ultrasound billing and reimbursement program generated significant
      revenue through ultrasound billing.

PMID- 24736126
TI  - An atypical misplacement of a temporary pacing catheter diagnosed and resolved by
      ultrasound.
AB  - Temporary transvenous pacing catheter placement is an important and critical
      procedure for emergency physicians. Ultrasound can be used to guide placement and
      to diagnosis correct or incorrect catheter placement. This case report discusses
      a patient with an acute ST elevation myocardial infarction leading to unstable
      arrhythmias requiring emergent transvenous cardiac pacing. The pacemaker was
      inserted using electrocardiographic monitoring through the bipolar pacing
      catheter. There was some difficulty placing the catheter, but successful capture
      with a left bundle-branch block pattern was obtained. However, ultrasonographic
      evaluation after placement showed the pacing wire curled in the Inferior Vena
      Cava (IVC) with the tip in the right ventricle. Ultrasound examination and
      guidance can prevent misplacement of the transvenous pacer catheter, which would
      not be apparent by electrocardiographic means.

PMID- 24736127
TI  - A retrospective analysis of the utility of an artificial neural network to
      predict ED volume.
AB  - OBJECTIVE: The objectives of this study are to design an artificial neural
      network (ANN) and to test it retrospectively to determine if it may be used to
      predict emergency department (ED) volume. METHODS: We conducted a retrospective
      review of patient registry data from February 4, 2007, to December 31, 2009, from
      an inner city, tertiary care hospital. We harvested data regarding weather, days
      of week, air quality, and special events to train the ANN. The ANN belongs to a
      class of neural networks called multilayer perceptrons. We designed an ANN
      composed of 37 input neurons, 22 hidden neurons, and 1 output neuron designed to
      predict the daily number of ED visits. The training method is a supervised
      backpropagation algorithm that uses mean squared error to minimize the average
      squared error between the ANN's output and the number of ED visits over all the
      example pairs. RESULTS: A linear regression between the predicted and actual ED
      visits demonstrated an R2 of 0.957 with a slope of 0.997. Ninety-five percent of
      the time, the ANN was within 20 visits. CONCLUSION: The results of this study
      show that a properly designed ANN is an effective tool that may be used to
      predict ED volume. The scatterplot demonstrates that the ANN is least predictive
      at the extreme ends of the spectrum suggesting that the ANN may be missing
      important variables. A properly calibrated ANN may have the potential to allow ED
      administrators to staff their units more appropriately in an effort to reduce
      patient wait times, decrease ED physician burnout rates, and increase the ability
      of caregivers to provide quality patient care. A prospective is needed to
      validate the utility of the ANN.

PMID- 24736128
TI  - Acute abdominal pain and dengue fever.

PMID- 24736129
TI  - Pulmonary Embolism Rule-out Criteria vs D-dimer testing in low-risk patients for
      pulmonary embolism: a retrospective study.
AB  - STUDY OBJECTIVES: The Pulmonary Embolism Rule-out Criteria (PERC) score has shown
      excellent negative predictive value; however, its use in the European population
      with high prevalence of PE is controversial. In Europe, PERC is not part of
      routine practice. For low-risk patients, guidelines recommend D-dimer testing,
      followed if positive by imaging study. We aimed to study the rate of diagnosis of
      PE after D-dimer testing in PERC-negative patients that could have been
      discharged if PERC was applied. METHOD: This was a multicenter retrospective
      study in Paris, France. We included all patients with a suspicion of PE who had D
      dimer testing in the emergency department, low pre-test probability, and a
      negative PERC score (that was retrospectively calculated). Patients with
      insufficient record to calculate PERC score were excluded. The primary end point
      was the rate of PE diagnosis before discharge in this population. Secondary end
      points included rate of invasive imaging studies and subsequent adverse events.
      RESULTS: We screened 4301 patients who had D-dimer testing, 1070 of whom were
      PERC negative and could be analyzed. The mean age was 35 years and 46% were men.
      D-dimer was positive (>500 ng/L) in 167 (16%) of them; CTPA or V/Q scan was
      performed in 153 (14%) cases. PE was confirmed in 5 cases (total rate 0.5%, 95%
      confidence interval 0.1%-1.1%). Fifteen patients (1%) experienced non-severe
      adverse events. CONCLUSION: D-dimer testing in PERC-negative patients led to a
      diagnosis of PE in 0.5% of them, with 15% of patients undergoing unnecessary
      irradiative imaging studies.

PMID- 24736130
TI  - Trophic transfer potential of aluminium oxide nanoparticles using representative
      primary producer (Chlorella ellipsoides) and a primary consumer (Ceriodaphnia
      dubia).
AB  - The transfer of nanoparticles through the food chain can lead to bioaccumulation
      and biomagnification resulting in a long term negative impact on the ecosystem
      functions. The primary objective of this study was evaluation of aluminium oxide
      nanoparticles transfer from primary producers to primary consumers. A simple set
      up consisting of a primary producer (Chlorella ellipsoides) and a primary
      consumer (Ceriodaphnia dubia) was used. Here, C. ellipsoides were exposed to the
      varying concentrations of the nanoparticles ranging from 20 to 120MUg/mL (196 to
      1176MUM) for 48h and the infested algal cells were used as the feed to C. dubia.
      The bioaccumulation of the nanoparticles into the daphnids was noted and the
      biomagnification factors were computed. The exposure was noted to cause subtle
      alterations in the feeding behaviour of the daphnids. This might have long term
      consequences in the energy flow through the food chain. The reproductive
      behaviour of the daphnids remained unaffected upon exposure to nanoparticle
      infested algal feed. Distinct observations at ultra-structural scale using
      transmission electron microscopy provided visual evidences for the disrupted
      feeding behaviour upon exposure to nanoparticle treated algae. Internalization of
      nanoparticle like inclusion bodies in the intracellular space of algae was also
      detected. The findings were further substantiated by a detailed analysis of
      hydrodynamic stability, bioavailability and dissolution of ions from the
      nanoparticles over the exposure period. Altogether, the study brings out the
      first of its kind of observation of trophic transfer potential/behaviour of
      aluminium oxide nanoparticles and its probable impacts on the energy flow in the
      fresh water aquatic ecosystem. 

PMID- 24736132
TI  - Degradation of phosphate ester hydraulic fluid in power station turbines
      investigated by a three-magnet unilateral magnet array.
AB  - A three-magnet array unilateral NMR sensor with a homogeneous sensitive spot was
      employed for assessing aging of the turbine oils used in two different power
      stations. The Carr-Purcell-Meiboom-Gill (CPMG) sequence and Inversion Recovery
      prepared CPMG were employed for measuring the 1H-NMR transverse and longitudinal
      relaxation times of turbine oils with different service status. Two signal
      components with different lifetimes were obtained by processing the transverse
      relaxation curves with a numeric program based on the Inverse Laplace
      Transformation. The long lifetime components of the transverse relaxation time
      T2eff and longitudinal relaxation time T1 were chosen to monitor the hydraulic
      fluid aging. The results demonstrate that an increase of the service time of the
      turbine oils clearly results in a decrease of T2eff,long and T1,long. This
      indicates that the T2eff,long and T1,long relaxation times, obtained from the
      unilateral magnetic resonance measurements, can be applied as indices for
      degradation of the hydraulic fluid in power station turbines.

PMID- 24736131
TI  - Quorum sensing activity of Hafnia alvei isolated from packed food.
AB  - Quorum sensing (QS) is a mechanism adopted by bacteria to regulate expression of
      genes according to population density. N-acylhomoserine lactones (AHLs) are a
      type of QS signalling molecules commonly found in Gram-negative bacteria which
      have been reported to play a role in microbial spoilage of foods and
      pathogenesis. In this study, we isolated an AHL-producing Hafnia alvei strain
      (FB1) from spherical fish pastes. Analysis via high resolution triple quadrupole
      liquid chromatography/mass spectrometry (LC/MS) on extracts from the spent
      supernatant of H. alvei FB1 revealed the existence of two short chain AHLs: N-(3
      oxohexanoyl) homoserine lactone (3-oxo-C6-HSL) and N-(3-oxo- octanoyl) homoserine
      lactone (3-oxo-C8-HSL). To our knowledge, this is the first report of the
      production of AHLs, especially 3-oxo-C8-HSL, by H. alvei. 

PMID- 24736133
TI  - Ozone sensing based on palladium decorated carbon nanotubes.
AB  - Multiwall carbon nanotubes (MWCNTs) were easily and efficiently decorated with Pd
      nanoparticles through a vapor-phase impregnation-decomposition method starting
      from palladium acetylacetonates. The sensor device consisted on a film of
      sensitive material (MWCNTs-Pd) deposited by drop coating on platinum
      interdigitated electrodes on a SiO2 substrate. The sensor exhibited a resistance
      change to ozone (O3) with a response time of 60 s at different temperatures and
      the capability of detecting concentrations up to 20 ppb. The sensor shows the
      best response when exposed to O3 at 120  degrees C. The device shows a very
      reproducible sensor performance, with high repeatability, full recovery and
      efficient response.

PMID- 24736134
TI  - [Stability of coagulation parameters: review of available data].
AB  - Samples for hemostasis testing are vulnerable to the effects of preanalytical
      variables and quality standards for sample processing and storage must be defined
      to insure accurate results. This article presents the available informations on
      these preanalytical issues. 

PMID- 24736135
TI  - [Urinary investigations in the diagnosis and monitoring of monoclonal
      gammopathies in daily practice].
AB  - The management of monoclonal gammopathies remains a public health issue with an
      incidence greater than 3% of the population over 50 years. Laboratory
      investigations, including urinary investigations play a key role in the diagnosis
      and monitoring of the patients. Urinary investigations are not recommended when
      screening monoclonal gammopathies. However, the initial laboratory evaluation of
      the monoclonal gammopathies systematically relies on renal function and
      proteinuria assessment. Urinary proteins electrophoresis combined with urinary
      proteins immunofixation are also recommended in the initial evaluation, with the
      exception of the Waldenstrom's disease. In some cases, serum investigations
      remain negative whereas urinary investigations confirm the presence of a
      monoclonal component. National and international recommendations have also been
      published about the monitoring of monoclonal gammopathies. The biological
      monitoring of monoclonal gammopathy of undetermined significance is mostly done
      by serum tests. Urinary investigations are commonly included in the response
      criteria in case of multiple myeloma or AL amyloidosis. Laboratory investigations
      like serum free light chain assay tend to decrease the need of urinary
      investigations in the monoclonal gammopathies. However, these urinary
      investigations currently maintain a leading role in the diagnosis and monitoring
      of monoclonal gammopathies. 

PMID- 24736136
TI  - [Circulating tumor cells: a new challenge for laboratory medicine].
AB  - Circulating tumor cells (CTCs) can be detected in the blood of patients with
      nearly all types of locally and metastatic adenocarcinomas. CTCs are epithelial
      cells whose release from a primitive tumor or a metastatic localization may be
      mediated by an epithelial-mesenchymal transition. Their pro-metastatic potential
      is still under debate because their phenotypes may be very heterogeneous, even
      within the same patient (expression of stem-cells markers, apoptotic status...).
      They often exhibit discrepancies with the primitive tumor, especially concerning
      the molecular basis of sensitivity/resistance to targeted therapies (expression
      of HER2 and hormone receptors, mutations responsible for resistance to tyrosine
      kinase inhibitors). Many methods for CTCs analysis are commercially available but
      very few are evaluated and standardized enough for clinical applications. The
      CellSearch device is the only one which is validated by the FDA for managing
      metastatic breast, prostate and colo-rectal cancer. It was used in most of the
      studies having demonstrated the prognostic and predictive value of CTCs in many
      tumoral localizations. Other studies are wanted to assess the ability of CTCs to
      optimize the therapeutic choices, to monitor drug efficiency in real-time as well
      as to become a surrogate end-point for evaluation of new therapies. Beyond CTCs
      enumeration, their biological features will need to be investigated.

PMID- 24736137
TI  - [Pitfalls in interpreting anti-HLA antibodies by Luminex technology].
AB  - The Luminex technology has become an important tool for HLA antibody screening
      and identification. This is the most sensitive technology to detect HLA
      antibodies for transplant patients and patients on awaiting list, and it has
      ushered a new strategy to determine HLA compatibility between donor and
      recipient. Moreover, the clinical relevance of all detected anti-HLA antibodies
      is not well understood, because this technique was shown to be prone to many
      artefacts or interferences, leading to a complicated interpretation for
      biologists and clinicians. Our objective in this article is to provide a careful
      consideration about this solid phase assay, and to focus attention on raised
      questions about technical performance and interpretation of the results. We
      should keep in mind that our results could change the clinical management of
      sensitized patients, their aptitude to receive a graft, and their follow-up.

PMID- 24736138
TI  - [Management of vitamin K antagonists in the elderly].
AB  - Elderly patients of 80 years and above are commonly frail, due to substantial
      comorbid conditions and numerous medications. Managing elderly patients receiving
      vitamin K antagonists (VKA) is challenging because those patients are at high
      risk of both thrombosis and bleeding. Special considerations on the choice of the
      VKA drug, dosing and monitoring have to be taken into account in the elderly in
      order to avoid over-anticoagulation and to minimize the haemorrhagic risk which
      consequences may be dramatic or fatal in this age group. In these patients, INR
      monitoring is crucial, especially at the start of treatment. The use of dosing
      algorithms specifically developed for elderly patients allows to decrease over
      anticoagulation during the initiation period. INR has to be monitored more
      frequently in case of acute illness or in case of modification of the associated
      drugs. Patient information and education are of great importance, even in
      geriatric patients and has been shown to improve the quality of anticoagulation.
      Even though the use of direct oral anticoagulants is currently expanding,
      prescribing VKA in elderly patients in whom the prevalence of severe renal
      insufficiency remains up to date. 

PMID- 24736139
TI  - [What disorders suspect following an increase of phenylalanine on newborn
      screening?].
AB  - Screening for PKU, in France, is made on the 3rd day of life by measuring the
      concentration of phenylalanine in dried blood spot samples. In this study, the
      goal was to examine the final diagnosis of patients who showed a
      hyperphenylalaninemia during newborn screening laboratory. Over a period of 11
      years from 1 February 2002 to 31 January 2013, all newborns with a phenylalanine
      concentration increase (>180 MUmol/L) have been identified and the cause of this
      increase was noted. Of the 165,113 newborns screened, hyperphenylalaninemia was
      identified in 90 patients during the newborn screening laboratory. During this
      period 35% of cases were due to classical phenylketonuria or
      hyperphenylalaninemia. In 4.4% of cases, increase concentrations were due to
      other diseases (biopterine deficiency, galactosemia, MSUD). However, 48.9% of
      high concentrations have not been confirmed by a second sample and 11% were
      children who died rapidely during their first days of life. The positive
      predictive value (PPV) of the test with a threshold of positivity >180 MUmol/L
      was 40%. Our study showed that the positivity threshold of 180 MUmol/L proposed
      by the Association francaise pour le depistage et la prevention des handicaps de
      l'enfant (AFDPHE) provides a comprehensive detection of all phenylketonuria cases
      as well as mild hyperphenylalaninemia permanent and transient cases. Eventhough
      the use of a higher threshold would have the advantage of increasing the PPV of
      the test, none the less we would have missed out on some cases to follow.

PMID- 24736140
TI  - [Analytical validation of a chromatographic method dedicated to search and
      identify natural and semi-synthetic opiates].
AB  - The identification of a product absorbed by an opiate consumer is sometimes
      problematic since there is no specific biomarker for all molecules. We developed
      an ultra-high pressure liquid chromatography coupled to tandem mass spectrometry
      technique which allows the identification and the quantification of 25 opiates in
      plasma. The sample preparation consists in a solid-phase extraction on Oasis MCX
      cartridges (Waters). The method has been validated according to FDA criteria
      completely for 21 substances and with some reservations for the remaining 4
      analytes. This method has been applied to 80 patients treated at the University
      Hospital of Liege for whom the screening of opiates was positive. The
      identification of the product consumed was effective in 86% of cases.

PMID- 24736141
TI  - [Focus on preanalytics for Down's syndrome screening during first trimester of
      pregnancy].
AB  - The aim of the study is to specify the pre-analytical conditions required for
      Down's syndrome screening in first trimester by maternal serum markers. The
      concentration variation of both markers, hCGbeta and PAPP-A, was analyzed at room
      temperature, at 4 degrees C and during freezing-thawing cycles. Serum can be kept
      during 72h between 2 and 8 degrees C with an acceptable bias of 5% for each
      marker. It can also undergo three freezing-thawing cycles without any variation
      of results. Preservation at room temperature (between 20 and 25 degrees C)
      requires an analysis within 24h. From this study, writing recommendations enable
      to give a precise frame to pre-analytical processing and transport of blood
      samples, in a field where variations can lead to heavy therapeutic decisions. 

PMID- 24736142
TI  - [Cytological and virological medium performance and stability assessment using
      the Cobas 4800 HPV test (Roche Diagnostics) used in France].
AB  - Analytical and stability performances of ten media were compared to PreservCyt
      medium using the Cobas 4800 HPV test: Easyfix (Labonord SAS, France), Qualicyt
      (Qualicyt, France), NovaPrep HQ+ (NovaCyt, France), CMDH (SARL Alphapath France),
      Cyt-All (Cytomega, France), Digene Cervical Sampler (Qiagen, USA), Aptima (Gen
      Probe, USA), Multi-Collect (Abbott, Allemagne), M4RT Micro Test (Remel, USA), et
      PCR-Media (Roche, Suisse). Most of media show a good correlation for all the
      performance characteristics studied. Cyt-All and NovaPrep HQ+ media are perfectly
      concordant with PreservCyt all parameters and genotypes considered. CMDH and M4RT
      have a reduced stability at +25 degrees C (3 and 2 days respectively) and would
      not be conformed to current shipping practices. Most of media tested show
      analytical and stability performances equivalent with the reference medium. The
      prospects of such study are interesting because in the near future, providers
      would make available media adapted to the problem of cervical smear but also to
      the conservation, transport of virus or bacteria for performing simultaneous
      searches of HPV, Chlamydia trachomatis or Neisseria gonorrhea.

PMID- 24736143
TI  - [Comparison of routine use of two chromogenic media ChromID CPS (bioMerieux) and
      UriSelect4 (Bio-Rad) for the detection of Escherichia coli and major
      uropathogenics in urine].
AB  - Escherichia coli is the most common bacterial cause of urinary tract infections.
      Its rapid and specific identification in urine samples represents a major
      challenge within the rendering results and optimizing the management of the
      patient. We aimed to compare the sensitivity and specificity of two commercially
      available chromogenic media for E. coli: ChromID CPS (Biomerieux) and UriSelect4
      (Bio(-)Rad), without carrying out further tests. 99 consecutive and non-redundant
      urine samples considered to be infected were simultaneously plated onto blood
      agar and the two chromogenic media. Colony color and bacterial growth
      quantification were compared 18 and 48 hours after incubation. Bacteria were
      identified with mass spectrometry. A complementary analysis on 80 bacterial
      strains known to pose potential identification problems was performed. 43 urines
      samples grew E. coli, and 42 of them were pink-colored on the two chromogenic
      mediums, as expected (sensibility=97.7%). Growth quantification was significantly
      greater on blood agar than on chromogenic media (p<0.001).We noted specificity
      issues at the complementary analysis with the UriSelect4 medium: Citrobacter
      freundii and some strains of Citrobacter brakii, Enterobacter cloacae and Hafnia
      alvei were pink-colored, and could be misidentified as E. coli. ChromID CPS
      medium did not show such misidentification. In conclusion, the agar ChromID CPS
      proved to be greater than the UriSelect4 agar in our work in terms of specificity
      of direct identification of E. Coli, without the use of additional test.

PMID- 24736144
TI  - [Comparison between the centrifugation on MPA C10 (Roche Diagnostics) and the
      centrifugation according recommendations of GEHT (Groupe d'etude de l'hemostase
      et de la thrombose) for the daily hemostasis assays].
AB  - Actually, many laboratories tend to acquire pre analytic automates to prepare
      specimens for analysis. For haemostasis, these pre analytical modules are not
      always in agreement with the recommendations from the Groupe d'etude de
      l'hemostase et de la thrombose (GEHT). For example in the MPA C10 module (Roche
      Diagnostics) the speed of centrifugation was not rather fast compared with the
      GEHT recommandations. Then, to be able to use this automate for routine
      coagulation assays, we compared results of Quick time, activated partial
      prothombin time, fibrinogen, factor II, factor V, factor VII, factor X and
      antithrombin levels and unfractioned heparin anti-Xa activity measurement after
      MPA (1,885 g - 999 sec) or GEHT (2,500 g - 900 sec) protocol of centrifugation.
      First, we verified platelet counts: in 82% of specimens, the platelet counts were
      under 10.10(9)/L after centrifugation on MPA module. Moreover, a good correlation
      was observed in all comparisons. Then we concluded the MPA C10 module was usable
      for routine coagulation tests.

PMID- 24736145
TI  - [Idiopathic capillary hyperpermeability syndrome revealing of Waldenstrom
      disease].
AB  - Waldenstrom disease is a rare hematologic disorder characterized by
      lymphoplasmacytic proliferation associated with the production of monoclonal IgM.
      Visceral injuries are described but some are rare (lung), others never reported
      (cardiac). We report for information and discussion a case representing these
      particular situations, considering that these attacks were revealing. It is a 63
      year old man who was admitted to the emergency room in an array of tamponade,
      with edema at the front and four members. Clinical and radiological examinations
      were objectified bilateral pleural effusion, ascite and pericarditis. The
      biological exploration showed pancytopenia, serum proteins 120 g/L and a
      monoclonal peak migrant beta2 globulin electrophoresis which is made by
      monoclonal immunoglobulin M (IgM kappa). The bone marrow confirmed the diagnosis
      of the Waldenstrom disease. This is a mode of revelation never described before.
      Considering this case, it would be wise to think of a Waldenstrom disease before
      any polyserositis.

PMID- 24736146
TI  - [Hemophacocytic syndrome as early sign for hepatosplenic T-cell lymphoma in a
      patient with chronic lymphocytic leukaemia].
AB  - Hepatosplenic T-cell lymphoma (HSCTL) is rare and caracterised by gama/delta T
      lymphocyte proliferation in the spleen, bone marrow and liver. Association
      between HSCTL and hemophagocytic syndrome is known, but association with chronic
      lymphoid leukaemia (CLL) has not been described to our knowledge. We report the
      case of a 76 year's old woman, with untreated CLL, presenting with febrile
      pancytopenia and splenomegaly. First test revealed a hemophagocytic syndrome
      without CLL transformation, and with a spontaneous and favorable evolution. Fever
      and cytopenias recur one month later. We find then a atypical circulating
      lymphocyte T population, negative for CD4 and CD8. The marrow immuno-phenotyping
      reveals a T CD4-CD8- gamma/delta lymphoid infiltration, leading to the diagnostic
      of HSTCL. 

PMID- 24736147
TI  - Knee brown tumor revealing a primary hyperparathyroidism: a case report.
AB  - Primary hyperparathyroidism is a common endocrine disorder, asymptomatic and
      diagnosed through a fortuitous hypercalcemia. Brown tumors are exceptional but
      severe hyperparathyroidism bone complications. We report in this paper an
      original observation of hyperparathyroidism due to a parathyroid adenoma
      presenting as a brown tumor. A 28 year-old girl admitted for a bone tumor of the
      knee, the blood test shows hypercalcemia with hyperparathyroidism, bone biopsy
      revealed giant cell lesions characteristic of brown tumors. 

PMID- 24736148
TI  - [Cour des comptes and laboratory medicine: which value have the virtues when the
      vices are ignored?].

PMID- 24736149
TI  - [The accreditation, source of knowledge and enrichment].
AB  - On the way for the accreditation which should lead us until 2020, we wish to
      share some reflections stemming from the daily practice concerning the compulsory
      quality approach for everyone. Several themes as training and skills evaluation,
      external quality controls, risk management and action plans have a great
      relevance and are a matter of public concern. Their consideration contributes not
      only to the reassurance of processes but also to knowledge improvement. In the
      following paragraphs we will present an overview of these themes which are all
      key elements for project management. 

PMID- 24736150
TI  - [Comments on the article of S. Vedy (Microbiology method validation: illustration
      with Bact'Alert 3D)].

PMID- 24736151
TI  - Introduction: e pluribus unum.

PMID- 24736152
TI  - Group behaviour in physical, chemical and biological systems.
AB  - Groups exhibit properties that either are not perceived to exist, or perhaps
      cannot exist, at the individual level. Such 'emergent' properties depend on how
      individuals interact, both among themselves and with their surroundings. The
      world of everyday objects consists of material entities. These are, ultimately,
      groups of elementary particles that organize themselves into atoms and molecules,
      occupy space, and so on. It turns out that an explanation of even the most
      commonplace features of this world requires relativistic quantum field theory and
      the fact that Planck's constant is discrete, not zero. Groups of molecules in
      solution, in particular polymers ('sols'), can form viscous clusters that behave
      like elastic solids ('gels'). Sol-gel transitions are examples of cooperative
      phenomena. Their occurrence is explained by modelling the statistics of inter
      unit interactions: the likelihood of either state varies sharply as a critical
      parameter crosses a threshold value. Group behaviour among cells or organisms is
      often heritable and therefore can evolve. This permits an additional, typically
      biological, explanation for it in terms of reproductive advantage, whether of the
      individual or of the group. There is no general agreement on the appropriate
      explanatory framework for understanding group-level phenomena in biology. 

PMID- 24736153
TI  - Evolution, epigenetics and cooperation.
AB  - Explanations for biological evolution in terms of changes in gene frequencies
      refer to outcomes rather than process. Integrating epigenetic studies with older
      evolutionary theories has drawn attention to the ways in which evolution occurs.
      Adaptation at the level of the gene is givingway to adaptation at the level of
      the organism and higher-order assemblages of organisms. These ideas impact on the
      theories of how cooperation might have evolved. Two of the theories, i.e. that
      cooperating individuals are genetically related or that they cooperate for self
      interested reasons, have been accepted for a long time. The idea that adaptation
      takes place at the level of groups is much more controversial. However, bringing
      together studies of development with those of evolution is taking away much of
      the heat in the debate about the evolution of group behaviour. 

PMID- 24736154
TI  - Symbiosis as the way of eukaryotic life: the dependent co-origination of the
      body.
AB  - Molecular analyses of symbiotic relationships are challenging our biological
      definitions of individuality and supplanting them with a new notion of normal
      part-whole relationships. This new notion is that of a 'holobiont', a consortium
      of organisms that becomes a functionally integrated 'whole'. This holobiont
      includes the zoological organism (the 'animal') as well as its persistent
      microbial symbionts. This new individuality is seen on anatomical and
      physiological levels, where a diversity of symbionts form a new 'organ system'
      within the zoological organism and become integrated into its metabolism and
      development. Moreover, as in normal development, there are reciprocal
      interactions between the 'host' organism and its symbionts that alter gene
      expression in both sets of cells. The immune system, instead of being seen as
      functioning solely to keep microbes out of the body, is also found to develop, in
      part, in dialogue with symbionts. Moreover, the immune system is actively
      involved in the colonization of the zoological organism, functioning as a
      mechanism for integrating microbes into the animal-cell community. Symbionts have
      also been found to constitute a second mode of genetic inheritance, providing
      selectable genetic variation for natural selection. We develop, grow and evolve
      as multi-genomic consortia/teams/ecosystems. 

PMID- 24736155
TI  - Limb, tooth, beak: three modes of development and evolutionary innovation of
      form.
AB  - The standard model of evolutionary change of form, deriving from Darwin's theory
      via the Modern Synthesis, assumes a gradualistic reshaping of anatomical
      structures, with major changes only occurring by many cycles of natural selection
      for marginal adaptive advantage. This model, with its assertion that a single
      mechanism underlies both micro- and macroevolutionary change, contains an
      implicit notion of development which is only applicable in some cases. Here we
      compare the embryological processes that shape the vertebrate limb bud, the
      mammalian tooth and the avian beak. The implied notion of development in the
      standard evolutionary picture is met only in the case of the vertebrate limb, a
      single-primordium organ with morphostatic shaping, in which cells rearrange in
      response to signalling centres which are essentially unchanged by cell movement.
      In the case of the tooth, a single-primordium organ with morphodynamic shaping in
      which the strengths and relationships between signalling centres is influenced by
      the cell and tissue movements they induce, and the beak, in which the final form
      is influenced by the collision and rearrangement of multiple tissue primordia,
      abrupt appearance of qualitatively different forms (i.e. morphological novelties)
      can occur with small changes in system parameters induced by a genetic change, or
      by an environmental factor whose effects can be subsequently canalized
      genetically. Bringing developmental mechanisms and, specifically, the material
      properties of tissues as excitable media into the evolutionary picture,
      demonstrates that gradualistic change for incremental adaptive advantage is only
      one of the possible modes of morphological evolution. 

PMID- 24736157
TI  - Nascent multicellular life and the emergence of individuality.
AB  - The evolution of multicellular organisms from unicellular ancestors involves a
      shift in the level at which selection operates. It is usual to think about this
      shift in terms of the emergence of traits that cause heritable differences in
      reproductive output at the level of nascent collectives. Defining these traits
      and the causes of their origin lies at the heart of understanding the evolution
      of multicellular life. In working toward a mechanistic, take-nothing-for-granted
      account, we begin by recognizing that the standard Lewontin formulation of
      properties necessary and sufficient for evolution by natural selection does not
      necessarily encompass Darwinian evolution in primitive collectives where parent
      offspring relationships may have been poorly defined. This, we suggest, limits
      the ability to conceptualize and capture the earliest manifestations of Darwinian
      properties. By way of solution we propose a relaxed interpretation of Lewontin's
      conditions and present these in the form of a set of necessary requirements for
      evolution by natural selection based upon the establishment of genealogical
      connections between recurrences of collectives. With emphasis on genealogy - as
      opposed to reproduction - it is possible to conceive selection acting on
      collectives prior to any manifestation of heritable variance in fitness. Such
      possibility draws attention to the evolutionary emergence of traits that
      strengthen causal relationships between recurrences - traits likely to underpin
      the emergence of forms of multiplication that establish parent-offspring
      relationships. Application of this framework to collectives of marginal status,
      particularly those whose recurrence is not defined by genealogy, makes clear that
      change at the level of collectives need not arise from selection acting at the
      higher level. We conclude by outlining applicability of our framework to loosely
      defined collectives of cells, such as those comprising the slugs of social amoeba
      and microbes that constitute the human microbiome. 

PMID- 24736156
TI  - Sociobiology of the budding yeast.
AB  - Social theory has provided a useful framework for research with microorganisms.
      Here I describe the advantages and possible risks of using a well-known model
      organism, the unicellular yeast Saccharomyces cerevisiae, for sociobiological
      research. I discuss the problems connected with clear classification of yeast
      behaviour based on the fitnessbased Hamilton paradigm. Relevant traits include
      different types of communities, production of flocculins, invertase and toxins,
      and the presence of apoptosis. 

PMID- 24736158
TI  - The remarkable discreteness of being.
AB  - Life is a discrete, stochastic phenomenon: for a biological organism, the time of
      the two most important events of its life (reproduction and death) is random and
      these events change the number of individuals of the species by single units.
      These facts can have surprising, counterintuitive consequences. I review here
      three examples where these facts play, or could play, important roles: the
      spatial distribution of species, the structuring of biodiversity and the
      (Darwinian) evolution of altruistic behaviour. 

PMID- 24736159
TI  - An ensemble approach to the evolution of complex systems.
AB  - Adaptive systems frequently incorporate complex structures which can arise
      spontaneously and which may be nonadaptive in the evolutionary sense. We give
      examples from phase transition and fractal growth to develop the themes of
      cooperative phenomena and pattern formation. We discuss RNA interference and
      transcriptional gene regulation networks, where a major part of the topological
      properties can be accounted for by mere combinatorics. A discussion of ensemble
      approaches to biological systems and measures of complexity is presented, and a
      connection is established between complexity and fitness. 

PMID- 24736161
TI  - Origins of evolutionary transitions.
AB  - An 'evolutionary transition in individuality' or 'major transition' is a
      transformation in the hierarchical level at which natural selection operates on a
      population. In this article I give an abstract (i.e. level-neutral and substrate
      neutral) articulation of the transition process in order to precisely understand
      how such processes can happen, especially how they can get started. 

PMID- 24736162
TI  - Individuals and groups in evolution: Darwinian pluralism and the multilevel
      selection debate.
AB  - Outlined here is an updated review of the long-standing 'kin selection vs group
      selection' debate. Group selection is a highly contentious concept,
      scientifically and philosophically. In 2012, Dawkins' attack against Wilson's
      latest book about eusociality concentrated all the attention on group selection
      and its mutual exclusivity with respect to inclusive fitness theory. Both
      opponents seem to be wrong, facing the general consensus in the field, which
      favours a pluralistic approach. Historically, despite some misunderstandings in
      current literature, such a perspective is clearly rooted in Darwin's writings,
      which suggested a plurality of levels of selection and a general view that we
      propose to call 'imperfect selfishness'. Today, the mathematically updated
      hypothesis of group selection has little to do with earlier versions of 'group
      selection'. It does not imply ontologically unmanageable notions of 'groups'. We
      propose here population structure as the main criterion of compatibility between
      kin selection and group selection. The latter is now evidently a pattern among
      others within a more general 'multilevel selection' theory. Different
      explanations and patterns are not mutually exclusive. Such a Darwinian pluralism
      is not a piece of the past, but a path into the future. A challenge in philosophy
      of biology will be to figure out the logical structure of this emerging
      pluralistic theory of evolution in such contentious debates. 

PMID- 24736160
TI  - Competing views on cancer.
AB  - Despite intense research efforts that have provided enormous insight, cancer
      continues to be a poorly understood disease. There has been much debate over
      whether the cancerous state can be said to originate in a single cell or whether
      it is a reflection of aberrant behaviour on the part of a 'society of cells'.
      This article presents, in the form of a debate conducted among the authors, three
      views of how the problem might be addressed. We do not claim that the views
      exhaust all possibilities. These views are (a) the tissue organization field
      theory (TOFT) that is based on a breakdown of tissue organization involving many
      cells from different embryological layers, (b) the cancer stem cell (CSC)
      hypothesis that focuses on genetic and epigenetic changes that take place within
      single cells, and (c) the proposition that rewiring of the cell's protein
      interaction networks mediated by intrinsically disordered proteins (IDPs) drives
      the tumorigenic process. The views are based on different philosophical
      approaches. In detail, they differ on some points and agree on others. It is left
      to the reader to decide whether one approach to understanding cancer appears more
      promising than the other. 

PMID- 24736163
TI  - A personal perspective on individual and group: comparative cultural observations
      with a focus on Ibn Khaldun.
AB  - As the Islamic world declined in the 14th century, Ibn Khaldun wrote the
      Muqaddimah, a massive philosophical work in which he sought scientific grounds
      for a universal analysis of human beings. By seeking a global history of
      humanity, one that was not derived from the particular history of any one group,
      he was able to offer insight into the importance of group solidarity, assabiyeh.
      In this essay, I discuss the dynamics between autonomous individuality and group
      identity and offer some cultural comparisons to illustrate more general insights.

PMID- 24736164
TI  - Does Russia need a treat-to-target initiative?

PMID- 24736165
TI  - Assessing structural changes in axial spondyloarthritis using a low-dose biplanar
      imaging system.
AB  - OBJECTIVES: Patients with axial SpA experience repeated spine imaging. EOS is a
      new low-dose imaging system with significantly lower irradiation than
      conventional radiography (CR). The objective was to explore the EOS performances
      compared with CR for the classification and follow-up of SpA. METHODS: We
      performed an observational, cross-sectional, single-centre study including SpA
      patients (definite diagnosis by expert opinion) and control patients [definite
      chronic mechanical low back pain (cLBP)]. All patients underwent pelvic and
      frontal and lateral CR of the entire spine and two-dimensional (2D) EOS imaging
      on the same day. Images were blindly assessed for sacroiliitis [modified New York
      criteria (mNY)] and for ankylosis of the spine [modified Stoke AS Spine Score
      (mSASSS)]. Global ease of interpretation was rated on a scale of 0-10. The
      primary outcome was intermodality agreement, with an a priori defined non
      inferiority limit of 0.7. Interobserver, intra-observer and intermodality
      agreement were measured by kappa, weighted kappa, intraclass correlation
      coefficient and Bland-Altman plots. RESULTS: Forty-eight SpA patients [mean age
      47.6 years (s.d. 14.9), symptom duration 21.4 years (s.d. 13.3), 35 (70%) men]
      and 48 cLBP controls [mean age 49.1 years (s.d. 10.7), 9 (22.5%) men] were
      included. Intermodality agreement between EOS and CR was 0.50 (95% CI 0.26, 0.75)
      and 0.97 (95% CI 0.95, 0.98) for sacroiliitis and mSASSS, respectively. Ease of
      interpretation was greater for CR [8.2 (s.d. 0.9)] compared with EOS [7.2 (s.d.
      0.8), P < 0.0001). CONCLUSION: Our results suggest that EOS could replace CR for
      the follow-up of structural damage of the spine, but its place in the
      classification of sacroiliitis needs to be further explored.

PMID- 24736167
TI  - Mortality and cancer incidence in the EPIC-NL cohort: impact of the healthy
      volunteer effect.
AB  - BACKGROUND: Prospective cohort studies recruit relatively healthy population
      samples, resulting in lower morbidity and mortality rates than in the source
      population. This is known as the healthy volunteer effect. The aim of this study
      was to define the magnitude and the development over time of the healthy
      volunteer effect in the EPIC-NL cohort. METHODS: We studied mortality rates in
      the EPIC-NL cohort, which comprises 37 551 men and women aged 20-70 years at
      recruitment in 1993-97. The date and cause of death of deceased participants
      until 2010 were obtained through linkage with the municipal registry and
      Statistics Netherlands. Standardized mortality ratios (SMRs) were computed by
      dividing the observed number of deaths by the number of deaths expected from the
      general Dutch population. Additionally, standardized incidence ratios were
      calculated to compare cancer incidence. RESULTS: After an average follow-up of
      14.9 years, 3029 deaths were documented. Overall mortality in men [SMR 73.5%, 95%
      confidence interval (CI): 68.1-79.3] and women (SMR 65.9%, 95% CI: 63.2-68.6) was
      lower compared with the general population for the whole follow-up period. The
      SMRs clearly increased over the follow-up period. Among women, the SMR was lower
      for death due to cardiovascular diseases than death due to cancer. Cancer
      incidence was also lower in EPIC-NL than in the general population (SMR 78.3 and
      82.7% for men and women, respectively). CONCLUSION: The results show a healthy
      volunteer effect in the EPIC-NL cohort, which tapers off with longer follow-up.
      Therefore, in the first years of follow-up, power might not be sufficient to
      detect small associations.

PMID- 24736166
TI  - Spontaneous development of autoimmune uveitis Is CCR2 dependent.
AB  - Development of novel strategies to treat noninfectious posterior uveitis is an
      ongoing challenge, in part because of limited availability of animal models that
      mimic the naturally occurring disease in humans. Mice deficient in the autoimmune
      regulatory gene Aire develop a spontaneous T-cell and macrophage-mediated
      autoimmune uveitis that closely recapitulates human endogenous uveitis and thus
      provide a useful model for mechanistic and therapeutic investigations.
      Lymphocytic and mononuclear infiltration of the retina in Aire knockout (KO) mice
      triggers the onset of uveitis from initial retinal inflammation to eventual
      destruction of the neuroretina with loss of photoreceptors. The C-C chemokine
      receptor type 2 protein (CCR2) functions in directing monocyte and macrophage
      migration to inflamed tissues via interaction with monocyte chemotactic proteins.
      Using the Aire KO mouse model, we demonstrated an essential role for CCR2 in the
      pathogenesis of autoimmune-mediated uveitis. Loss of functional CCR2 effectively
      reduced immune cell infiltration and rescued the retina from destruction. CCR2
      dependent migration of bone marrow-derived cells provided the driving force for
      retinal inflammation, with CCR2-expressing mononuclear cells contributing to
      retinal damage via recruitment of CD4(+) T cells. These studies identify the CCR2
      pathway as a promising therapeutic target that may prove an effective approach to
      treat uveitis associated with autoimmunity. 

PMID- 24736168
TI  - Escherichia coli O104:H4 outbreak in Germany--clarification of the origin of the
      epidemic.
AB  - BACKGROUND: In 2011, Germany was hit by one of its largest outbreaks of acute
      gastroenteritis and haemolytic uraemic syndrome caused by a new emerging
      enterohaemorrhagic Escherichia coli O104:H4 strain. The German Haemolytic Uraemic
      Syndrome/Enterohaemorrhagic E. coli (GHUSEC) outbreak had unusual
      microbiological, infectiological and epidemiological features and its origin is
      still only partially solved. The aim of this article is to contribute to the
      clarification of the origin of the epidemic. METHODS: To retrospectively assess
      whether the GHUSEC outbreak was natural, accidental or a deliberate one, we
      analysed it according to three published scoring and differentiation models. Data
      for application of these models were obtained by literature review in the
      database Medline for the period 2011-13. RESULTS: The analysis of the unusual
      GHUSEC outbreak shows that the present official assumption of its natural origin
      is questionable and pointed out to a probability that the pathogen could have
      also been introduced accidentally or intentionally in the food chain. CONCLUSION:
      The possibility of an accidental or deliberate epidemic should not be discarded.
      Further epidemiological, microbiological and forensic analyses are needed to
      clarify the GHUSEC outbreak.

PMID- 24736169
TI  - Neonatal EEG at scalp is focal and implies high skull conductivity in realistic
      neonatal head models.
AB  - The potential improvements in spatial resolution of neonatal EEG used in source
      localization have been challenged by the insufficiencies in realistic neonatal
      head models. Our present study aimed at using empirical methods to indirectly
      estimate skull conductivity; the model parameter that is known to significantly
      affect the behavior of newborn scalp EEG and cause it to be markedly different
      from that of an adult. To this end, we used 64 channel EEG recordings to study
      the spatial specificity of scalp EEG by assessing the spatial decays in focal
      transients using both amplitudes and between-c'hannels linear correlations. The
      findings showed that these amplitudes and correlations decay within few
      centimeters from the reference channel/electrode, and that the nature of the
      decay is independent of the scalp area. This decay in newborn infants was found
      to be approximately three times faster than the corresponding decay in adult EEG
      analyzed from a set of 256 channel recordings. We then generated realistic head
      models using both finite and boundary element methods along with a manually
      segmented magnetic resonance images to study the spatial decays of scalp
      potentials produced by single dipole in the cortex. By comparing the spatial
      decays due to real and simulated EEG for different skull conductivities (from
      0.003 to 0.3S/m), we showed that a close match between the empirical and
      simulated decays was obtained when the selected skull conductivity for newborn
      was around 0.06-0.2S/m. This is over an order of magnitude higher than the
      currently used values in adult head modeling. The results also showed that the
      neonatal scalp EEG is less smeared than that of an adult and this characteristic
      is the same across the entire scalp, including the fontanel region. These results
      indicate that a focal cortical activity is generally only registered by
      electrodes within few centimeters from the source. Hence, the conventional 10 to
      20 channel neonatal EEG acquisition systems give a significantly spatially under
      sampled scalp EEG and may, consequently, give distorted pictures of focal brain
      activities. Such spatial specificity can only be reconciled by appreciating the
      anatomy of the neonatal head, especially the still unossified skull structure
      that needs to be modeled with higher conductivities than conventionally used in
      the adults. 

PMID- 24736170
TI  - Event-related potentials associated with performance monitoring in non-human
      primates.
AB  - The abilities to monitor performance outcomes and, when appropriate, impose
      strategic adjustments in behavior, are core features of the intact human
      cognitive control system. Errors committed in choice reaction time tasks are
      typically followed by two scalp potentials, the error negativity (Ne) and error
      positivity (Pe). These components are considered physiological signatures of the
      performance monitoring system. Several theories have been proposed to account for
      these error-related potentials and their functional and behavioral significance.
      These ideas were inspired by empirical data in humans and other mammalian
      species, and supported by the results of experiments in which performance
      monitoring, in humans and computational models, was investigated. However, an
      appropriate animal model is required to rigorously test the predictions that
      arise from these theories. Here, using a variant of the anti-saccade task, we
      demonstrate that event-related signals recorded from macaque monkeys, following
      errors in choice, resemble the human Ne and Pe. These components were modulated
      by cognitive variables, namely the degree of cognitive control associated with
      the applied rule, which implies the existence of hierarchical error processing
      systems in monkeys, and the degree of response control associated with the
      saccade. Error-related potential amplitudes were also correlated with remedial
      action, in a rule-dependent manner. These results demonstrate that error-related
      potentials in macaque monkeys and human subjects show important similarities,
      thus supporting the use of the macaque monkey as an animal model for the
      neurophysiological study of performance monitoring, and potentially, post-error
      adjustments. 

PMID- 24736171
TI  - Towards a reproducible protocol for repetitive and semi-quantitative rat brain
      imaging with (18) F-FDG: exemplified in a memantine pharmacological challenge.
AB  - The standard uptake value (SUV), commonly used to quantify (18)F
      FluoroDeoxyGlucose (FDG) uptake in small animal brain PET imaging, is affected by
      many factors. In this study the influence of fasting times, inter-scan duration
      and repetitive scanning on the variability of different SUV measures is
      investigated. Additionally it is demonstrated that these variables could
      adversely influence the outcome of a pharmacological challenge when not accounted
      for. Naive Sprague-Dawley rats (n=20) were randomly divided into five different
      fasting groups (no fasting up to 24h of fasting). SUV brain uptake values were
      reproducible in naive animals when a fasting period of at least 12h is used and
      for shorter fasting periods SUV values need to be corrected for the glucose
      level. Additionally, a separate animal group (n=6) was sufficiently fasted for
      16h and in a longitudinal setting being scanned six times in three weeks.
      Especially with short inter-scan durations, increasing glucose levels were found
      over time which was attributed to increased stress due to repeated food
      deprivation, altered food intake or scan manipulations. As a result, even with
      controlled and sufficient fasting, blood glucose levels should be taken into
      account for data quantification. Strikingly, even the brain activation effects of
      an NMDA-antagonist challenge with memantine could not be detected in experiments
      with a short inter-scan duration if glucose levels were not taken into account.
      Correcting for glucose levels decreases the inter- and intra-animal variability
      for rat brain imaging. SUV corrected for glucose levels yields the lowest inter
      animal variation. However, if the body weight changes significantly, as in a long
      experiment, quantification based on the glucose corrected percentage injected
      dose (and not SUV) is recommendable as this yields the lowest intra-animal
      variation. 

PMID- 24736172
TI  - Whole brain, high resolution multiband spin-echo EPI fMRI at 7 T: a comparison
      with gradient-echo EPI using a color-word Stroop task.
AB  - A whole brain, multiband spin-echo (SE) echo planar imaging (EPI) sequence
      employing a high spatial (1.5 mm isotropic) and temporal (TR of 2 s) resolution
      was implemented at 7 T. Its overall performance (tSNR, sensitivity and CNR) was
      assessed and compared to a geometrically matched gradient-echo (GE) EPI multiband
      sequence (TR of 1.4 s) using a color-word Stroop task. PINS RF pulses were used
      for refocusing to reduce RF amplitude requirements and SAR, summed and phase
      optimized standard pulses were used for excitation enabling a transverse or
      oblique slice orientation. The distortions were minimized with the use of
      parallel imaging in the phase encoding direction and a post-acquisition
      distortion correction. In general, GE-EPI shows higher efficiency and higher CNR
      in most brain areas except in some parts of the visual cortex and superior
      frontal pole at both the group and individual-subject levels. Gradient-echo EPI
      was able to detect robust activation near the air/tissue interfaces such as the
      orbito-frontal and subcortical regions due to reduced intra-voxel dephasing
      because of the thin slices used and high in-plane resolution.

PMID- 24736173
TI  - Reliability of functional magnetic resonance imaging activation during working
      memory in a multi-site study: analysis from the North American Prodrome
      Longitudinal Study.
AB  - Multi-site neuroimaging studies offer an efficient means to study brain
      functioning in large samples of individuals with rare conditions; however, they
      present new challenges given that aggregating data across sites introduces
      additional variability into measures of interest. Assessing the reliability of
      brain activation across study sites and comparing statistical methods for pooling
      functional data are critical to ensuring the validity of aggregating data across
      sites. The current study used two samples of healthy individuals to assess the
      feasibility and reliability of aggregating multi-site functional magnetic
      resonance imaging (fMRI) data from a Sternberg-style verbal working memory task.
      Participants were recruited as part of the North American Prodrome Longitudinal
      Study (NAPLS), which comprises eight fMRI scanning sites across the United States
      and Canada. In the first study sample (n=8), one participant from each home site
      traveled to each of the sites and was scanned while completing the task on two
      consecutive days. Reliability was examined using generalizability theory. Results
      indicated that blood oxygen level-dependent (BOLD) signal was reproducible across
      sites and was highly reliable, or generalizable, across scanning sites and
      testing days for core working memory ROIs (generalizability ICCs=0.81 for left
      dorsolateral prefrontal cortex, 0.95 for left superior parietal cortex). In the
      second study sample (n=154), two statistical methods for aggregating fMRI data
      across sites for all healthy individuals recruited as control participants in the
      NAPLS study were compared. Control participants were scanned on one occasion at
      the site from which they were recruited. Results from the image-based meta
      analysis (IBMA) method and mixed effects model with site covariance method both
      showed robust activation in expected regions (i.e. dorsolateral prefrontal
      cortex, anterior cingulate cortex, supplementary motor cortex, superior parietal
      cortex, inferior temporal cortex, cerebellum, thalamus, basal ganglia).
      Quantification of the similarity of group maps from these methods confirmed a
      very high (96%) degree of spatial overlap in results. Thus, brain activation
      during working memory function was reliable across the NAPLS sites and both the
      IBMA and mixed effects model with site covariance methods appear to be valid
      approaches for aggregating data across sites. These findings indicate that multi
      site functional neuroimaging can offer a reliable means to increase power and
      generalizability of results when investigating brain function in rare populations
      and support the multi-site investigation of working memory function in the NAPLS
      study, in particular. 

PMID- 24736174
TI  - Neural correlates of apparent motion perception of impoverished facial stimuli: a
      comparison of ERP and ERSP activity.
AB  - Our brains readily decode human movements, as shown by neural responses to face
      and body motion. N170 event-related potentials (ERPs) are earlier and larger to
      mouth opening movements relative to closing in both line-drawn and natural faces,
      and gaze aversions relative to direct gaze in natural faces (Puce and Perrett,
      2003; Puce et al., 2000). Here we extended this work by recording both ERP and
      oscillatory EEG activity (event-related spectral perturbations, ERSPs) to line
      drawn faces depicting eye and mouth movements (Eyes: Direct vs Away; Mouth:
      Closed vs Open) and non-face motion controls. Neural activity was measured in 2
      occipito-temporal clusters of 9 electrodes, one in each hemisphere. Mouth opening
      generated larger N170s than mouth closing, replicating earlier work. Eye motion
      elicited robust N170s that did not differ between gaze conditions. Control
      condition differences were seen, and generated the largest N170. ERSP difference
      plots across conditions in the occipito-temporal electrode clusters (Eyes: Direct
      vs Away; Mouth: Closed vs Open) showed statistically significant differences in
      beta and gamma bands for gaze direction changes and mouth opening at similar post
      stimulus times and frequencies. In contrast, control stimuli showed activity in
      the gamma band with a completely different time profile and hemispheric
      distribution to facial stimuli. ERSP plots were generated in two 9 electrode
      clusters centered on central sites, C3 and C4. In the left cluster for all
      stimulus conditions, broadband beta suppression persisted from about 250ms post
      motion onset. In the right cluster, beta suppression was seen for control
      conditions only. Statistically significant differences between conditions were
      confined between 4 and 15Hz, unlike the occipito-temporal sites where differences
      occurred at much higher frequencies (high beta/gamma). Our data indicate that
      N170 amplitude is sensitive to the amount of movement in the visual field,
      independent of stimulus type. In contrast, occipito-temporal beta and gamma
      activity differentiates between facial and non-facial motion. Context and
      stimulus configuration likely plays a role in shaping neural responses, based on
      comparisons of the current data to previously reported studies. Broadband
      suppression of central beta activity, and significant low frequency differences
      were likely stimulus driven and not contingent on behavioral responses. 

PMID- 24736175
TI  - Event time analysis of longitudinal neuroimage data.
AB  - This paper presents a method for the statistical analysis of the associations
      between longitudinal neuroimaging measurements, e.g., of cortical thickness, and
      the timing of a clinical event of interest, e.g., disease onset. The proposed
      approach consists of two steps, the first of which employs a linear mixed effects
      (LME) model to capture temporal variation in serial imaging data. The second step
      utilizes the extended Cox regression model to examine the relationship between
      time-dependent imaging measurements and the timing of the event of interest. We
      demonstrate the proposed method both for the univariate analysis of image-derived
      biomarkers, e.g., the volume of a structure of interest, and the exploratory mass
      univariate analysis of measurements contained in maps, such as cortical thickness
      and gray matter density. The mass-univariate method employs a recently developed
      spatial extension of the LME model. We applied our method to analyze structural
      measurements computed using FreeSurfer, a widely used brain Magnetic Resonance
      Image (MRI) analysis software package. We provide a quantitative and objective
      empirical evaluation of the statistical performance of the proposed method on
      longitudinal data from subjects suffering from Mild Cognitive Impairment (MCI) at
      baseline. 

PMID- 24736178
TI  - Juggling revisited - a voxel-based morphometry study with expert jugglers.
AB  - Juggling is a highly interesting tool to investigate neuroplasticity associated
      with motor-learning. Several brain-imaging studies have reported changes in
      regional brain morphology in visual association cortices in individuals learning
      how to juggle a three-ball cascade. However, to our knowledge there are no
      studies that investigated expert jugglers, looking for specific features in
      regional brain morphology related to this highly specialized skill. Using T1
      weighted images and voxel-based morphometry we investigated in a cross-sectional
      study design 16 expert jugglers, able to juggle at least five balls and an age-
      and gender-matched group of non-jugglers. We hypothesized that expert jugglers
      would show higher gray matter density in regions involved in visual motion
      perception and eye-hand coordination. Images were pre-processed and analyzed
      using SPM8. Age was included in the analyses as covariate of no interest. As
      compared to controls jugglers displayed several clusters of higher, regional gray
      matter density in the occipital and parietal lobes including the secondary visual
      cortex, the hMT+/V5 area bilaterally and the intraparietal sulcus bilaterally.
      Within the jugglers group we also found a correlation between performance and
      regional gray matter density in the right hMT+/V5 area. Our study provides
      evidence that expert jugglers show increased gray matter density in brain regions
      involved in visual motion perception and eye-hand coordination, i.e. brain areas
      that have previously been shown to undergo dynamic changes in terms of gray
      matter increases in subjects learning a basic three-ball cascade. The extent to
      which transient increases in beginners and the differences in experts and non
      experts are based on the same neurobiological correlates remains to be fully
      elucidated. 

PMID- 24736176
TI  - Resting state functional connectivity of the basal nucleus of Meynert in humans:
      in comparison to the ventral striatum and the effects of age.
AB  - The basal nucleus of Meynert (BNM) provides the primary cholinergic inputs to the
      cerebral cortex. Loss of neurons in the BNM is linked to cognitive deficits in
      Alzheimer's disease and other degenerative conditions. Numerous animal studies
      described cholinergic and non-cholinergic neuronal responses in the BNM; however,
      work in humans has been hampered by the difficulty of defining the BNM
      anatomically. Here, on the basis of a previous study that delineated the BNM of
      post-mortem human brains in a standard stereotaxic space, we sought to examine
      functional connectivity of the BNM, as compared to the nucleus accumbens (or
      ventral striatum, VS), in a large resting state functional magnetic resonance
      imaging data set. The BNM and VS shared but also showed a distinct pattern of
      cortical and subcortical connectivity. Compared to the VS, the BNM showed
      stronger positive connectivity with the putamen, pallidum, thalamus, amygdala and
      midbrain, as well as the anterior cingulate cortex, supplementary motor area and
      pre-supplementary motor area, a network of brain regions that respond to salient
      stimuli and orchestrate motor behavior. In contrast, compared to the BNM, the VS
      showed stronger positive connectivity with the ventral caudate and medial
      orbitofrontal cortex, areas implicated in reward processing and motivated
      behavior. Furthermore, the BNM and VS each showed extensive negative connectivity
      with visual and lateral prefrontal cortices. Together, the distinct cerebral
      functional connectivities support the role of the BNM in arousal, saliency
      responses and cognitive motor control and the VS in reward related behavior.
      Considering the importance of BNM in age-related cognitive decline, we explored
      the effects of age on BNM and VS connectivities. BNM connectivity to the visual
      and somatomotor cortices decreases while connectivity to subcortical structures
      including the midbrain, thalamus, and pallidum increases with age. These findings
      of age-related changes of cerebral functional connectivity of the BNM may
      facilitate research of the neural bases of cognitive decline in health and
      illness. 

PMID- 24736177
TI  - Common genetic variants and gene expression associated with white matter
      microstructure in the human brain.
AB  - Identifying genes that contribute to white matter microstructure should provide
      insights into the neurobiological processes that regulate white matter
      development, plasticity and pathology. We detected five significant SNPs using
      genome-wide association analysis on a global measure of fractional anisotropy in
      776 individuals from large extended pedigrees. Genetic correlations and genome
      wide association results indicated that the genetic signal was largely
      homogeneous across white matter regions. Using RNA transcripts derived from
      lymphocytes in the same individuals, we identified two genes (GNA13 and CCDC91)
      that are likely to be cis-regulated by top SNPs, and whose expression levels were
      also genetically correlated with fractional anisotropy. A transcript of HTR7 was
      phenotypically associated with FA, and was associated with an intronic genome
      wide significant SNP. These results encourage further research in the mechanisms
      by which GNA13, HTR7 and CCDC91 influence brain structure, and emphasize a role
      for g-protein signaling in the development and maintenance of white matter
      microstructure in health and disease. 

PMID- 24736179
TI  - The physiological plausibility of time-varying Granger-causal modeling:
      normalization and weighting by spectral power.
AB  - Time-varying connectivity methods are increasingly used to study directed
      interactions between brain regions from electrophysiological signals. These
      methods often show good results in simulated data but it is unclear to what
      extent connectivity results obtained from real data are physiologically
      plausible. Here we introduce a benchmark approach using multichannel
      somatosensory evoked potentials (SEPs) measured across rat cortex, where the
      structural and functional connectivity is relatively simple and well-understood.
      Rat SEPs to whisker stimulation are exclusively initiated by contralateral
      primary sensory cortex (S1), at known latencies, and with activity spread from S1
      to specific cortical regions. This allows for a comparison of time-varying
      connectivity measures according to fixed criteria. We thus evaluated the
      performance of time-varying Partial Directed Coherence (PDC) and the Directed
      Transfer Function (DTF), comparing row- and column-wise normalization and the
      effect of weighting by the power spectral density (PSD). The benchmark approach
      revealed clear differences between methods in terms of physiological
      plausibility, effect size and temporal resolution. The results provide a
      validation of time-varying directed connectivity methods in an animal model and
      suggest a driving role for ipsilateral S1 in the later part of the SEP. The
      benchmark SEP dataset is made freely available. 

PMID- 24736180
TI  - Coupling between gamma-band power and cerebral blood volume during recurrent
      acute neocortical seizures.
AB  - Characterization of neural and hemodynamic biomarkers of epileptic activity that
      can be measured using non-invasive techniques is fundamental to the accurate
      identification of the epileptogenic zone (EZ) in the clinical setting. Recently,
      oscillations at gamma-band frequencies and above (>30 Hz) have been suggested to
      provide valuable localizing information of the EZ and track cortical activation
      associated with epileptogenic processes. Although a tight coupling between gamma
      band activity and hemodynamic-based signals has been consistently demonstrated in
      non-pathological conditions, very little is known about whether such a
      relationship is maintained in epilepsy and the laminar etiology of these signals.
      Confirmation of this relationship may elucidate the underpinnings of perfusion
      based signals in epilepsy and the potential value of localizing the EZ using
      hemodynamic correlates of pathological rhythms. Here, we use concurrent multi
      depth electrophysiology and 2-dimensional optical imaging spectroscopy to examine
      the coupling between multi-band neural activity and cerebral blood volume (CBV)
      during recurrent acute focal neocortical seizures in the urethane-anesthetized
      rat. We show a powerful correlation between gamma-band power (25-90 Hz) and CBV
      across cortical laminae, in particular layer 5, and a close association between
      gamma measures and multi-unit activity (MUA). Our findings provide insights into
      the laminar electrophysiological basis of perfusion-based imaging signals in the
      epileptic state and may have implications for further research using non-invasive
      multi-modal techniques to localize epileptogenic tissue.

PMID- 24736181
TI  - Thalamus and posterior temporal lobe show greater inter-network connectivity at
      rest and across sensory paradigms in schizophrenia.
AB  - Although a number of recent studies have examined functional connectivity at
      rest, few have assessed differences between connectivity both during rest and
      across active task paradigms. Therefore, the question of whether cortical
      connectivity patterns remain stable or change with task engagement continues to
      be unaddressed. We collected multi-scan fMRI data on healthy controls (N=53) and
      schizophrenia patients (N=42) during rest and across paradigms arranged
      hierarchically by sensory load. We measured functional network connectivity among
      45 non-artifactual distinct brain networks. Then, we applied a novel analysis to
      assess cross paradigm connectivity patterns applied to healthy controls and
      patients with schizophrenia. To detect these patterns, we fit a group by task
      full factorial ANOVA model to the group average functional network connectivity
      values. Our approach identified both stable (static effects) and state-based
      differences (dynamic effects) in brain connectivity providing a better
      understanding of how individuals' reactions to simple sensory stimuli are
      conditioned by the context within which they are presented. Our findings suggest
      that not all group differences observed during rest are detectable in other
      cognitive states. In addition, the stable differences of heightened connectivity
      between multiple brain areas with thalamus across tasks underscore the importance
      of the thalamus as a gateway to sensory input and provide new insight into
      schizophrenia. 

PMID- 24736182
TI  - Sensitive periods of amygdala development: the role of maltreatment in
      preadolescence.
AB  - The amygdala is vulnerable to stress-dependent disruptions in neural development.
      Animal models have shown that stress increases dendritic arborization leading to
      larger amygdala volumes. Human studies of early stress and amygdala volume,
      however, remain inconclusive. This study compared amygdala volume in adults with
      childhood maltreatment to that in healthy controls. Eighteen participants from a
      longitudinal cohort and 33 cross-sectional controls (17 M/34 F, 25.5+/-3.1 years)
      completed a structural magnetic resonance imagining scan and the Maltreatment and
      Abuse Chronology of Exposure scale. Random forest regression with conditional
      trees was used to assess relative importance of exposure to adversity at each age
      on amygdala, thalamic or caudate volume. Severity of exposure to adversity across
      age accounted for 27% of the variance in right amygdala volume. Peak sensitivity
      occurred at 10-11 years of age, and importance of exposure at this time was
      highly significant based on permutation tests (p=0.003). The regression model
      showed that exposure during this sensitive period resulted in steep dose-response
      function with maximal response to even modest levels of exposure. Subjects in the
      highest exposure quartile (MACE-11, range=11-54) had a 9.1% greater right
      amygdala volume than subjects in the lowest exposure quartile (MACE-11, <=3.5).
      No associations emerged between age of exposure and volume of the left amygdala
      or bilateral caudate or thalamus. Severity of adversity experienced at age 10-11
      contributed to larger right but not left amygdala volume in adulthood. Results
      provide preliminary evidence that the amygdala may have a developmental sensitive
      period in preadolescence.

PMID- 24736183
TI  - Comparison of human septal nuclei MRI measurements using automated segmentation
      and a new manual protocol based on histology.
AB  - Septal nuclei, located in basal forebrain, are strongly connected with hippocampi
      and important in learning and memory, but have received limited research
      attention in human MRI studies. While probabilistic maps for estimating septal
      volume on MRI are now available, they have not been independently validated
      against manual tracing of MRI, typically considered the gold standard for
      delineating brain structures. We developed a protocol for manual tracing of the
      human septal region on MRI based on examination of neuroanatomical specimens. We
      applied this tracing protocol to T1 MRI scans (n=86) from subjects with temporal
      epilepsy and healthy controls to measure septal volume. To assess the inter-rater
      reliability of the protocol, a second tracer used the same protocol on 20 scans
      that were randomly selected from the 72 healthy controls. In addition to
      measuring septal volume, maximum septal thickness between the ventricles was
      measured and recorded. The same scans (n=86) were also analyzed using septal
      probabilistic maps and DARTEL toolbox in SPM. Results show that our manual
      tracing algorithm is reliable, and that septal volume measurements obtained via
      manual and automated methods correlate significantly with each other (p<.001).
      Both manual and automated methods detected significantly enlarged septal nuclei
      in patients with temporal lobe epilepsy in accord with a proposed compensatory
      neuroplastic process related to the strong connections between septal nuclei and
      hippocampi. Septal thickness, which was simple to measure with excellent inter
      rater reliability, correlated well with both manual and automated septal volume,
      suggesting it could serve as an easy-to-measure surrogate for septal volume in
      future studies. Our results call attention to the important though understudied
      human septal region, confirm its enlargement in temporal lobe epilepsy, and
      provide a reliable new manual delineation protocol that will facilitate continued
      study of this critical region. 

PMID- 24736185
TI  - Towards obtaining spatiotemporally precise responses to continuous sensory
      stimuli in humans: a general linear modeling approach to EEG.
AB  - Noninvasive investigation of human sensory processing with high temporal
      resolution typically involves repeatedly presenting discrete stimuli and
      extracting an average event-related response from scalp recorded neuroelectric or
      neuromagnetic signals. While this approach is and has been extremely useful, it
      suffers from two drawbacks: a lack of naturalness in terms of the stimulus and a
      lack of precision in terms of the cortical response generators. Here we show that
      a linear modeling approach that exploits functional specialization in sensory
      systems can be used to rapidly obtain spatiotemporally precise responses to
      complex sensory stimuli using electroencephalography (EEG). We demonstrate the
      method by example through the controlled modulation of the contrast and coherent
      motion of visual stimuli. Regressing the data against these modulation signals
      produces spatially focal, highly temporally resolved response measures that are
      suggestive of specific activation of visual areas V1 and V6, respectively, based
      on their onset latency, their topographic distribution and the estimated location
      of their sources. We discuss our approach by comparing it with fMRI/MRI informed
      source analysis methods and, in doing so, we provide novel information on the
      timing of coherent motion processing in human V6. Generalizing such an approach
      has the potential to facilitate the rapid, inexpensive spatiotemporal
      localization of higher perceptual functions in behaving humans. 

PMID- 24736184
TI  - Test-retest reproducibility of cannabinoid-receptor type 1 availability
      quantified with the PET ligand [11C]MePPEP.
AB  - BACKGROUND: Endocannabinoids are involved in normal cognition, and dysfunction in
      cannabinoid-receptor-mediated neurotransmission has been suggested in a variety
      of neurological and psychiatric pathologies. The type 1 cannabinoid receptor
      (CB1) is widely expressed in the human central nervous system. The objective of
      this study was to quantify the test-retest reproducibility of measures of the PET
      ligand [(11)C]MePPEP in order to assess the stability of CB1-receptor
      quantification in humans in vivo. METHODS: Fifteen healthy subjects (eight
      females; median age 32 years, range 25 to 65 years) had a 90-minute PET scan on
      two occasions after injection of a median dose of [(11)C]MePPEP of 364 MBq.
      Metabolite-corrected arterial plasma input functions were obtained for all scans.
      Eight ROIs, reflecting different levels of receptor densities/concentrations,
      were defined automatically: hippocampus, anterior cingulate gyrus, inferior
      frontal gyrus, caudate nucleus, globus pallidus, nucleus accumbens, thalamus, and
      pons. We used seven quantification methods: reversible compartmental models with
      one and two tissue classes, two and four rate constants, and a variable blood
      volume term (2kbv; 4kbv); model-free (spectral) analyses with and without
      regularisation, including one with voxel-wise quantification; the simplified
      reference tissue model (SRTM) with pons as a pseudo-reference region; and
      modified standard uptake values (mSUVs) calculated for the period of ~30-60 min
      after injection. Percentage test-retest change and between-subject variability
      were both assessed, and test-retest reliability was quantified by the intraclass
      correlation coefficient (ICC). The ratio of binding estimates pallidum:pons
      served as an indicator of a method's ability to reflect binding heterogeneity.
      RESULTS: Neither the SRTM nor the 4kbv model produced reliable measures, with
      ICCs around zero. Very good (>0.75) or excellent (>0.80) ICCs were obtained with
      the other methods. The most reliable were spectral analysis parametric maps
      (average across regions+/-standard deviation 0.83+/-0.03), rank shaping
      regularised spectral analysis (0.82+/-0.05), and the 2kbv model (0.82+/-0.09),
      but mSUVs were also reliable for most regions (0.79+/-0.13). Mean test-retest
      changes among the five well-performing methods ranged from 12+/-10% for mSUVs to
      16% for 2kbv. Intersubject variability was high, with mean between-subject
      coefficients of variation ranging from 32+/-13% for mSUVs to 45% for 2kbv. The
      highest pallidum:pons ratios of binding estimates were achieved by mSUV (4.2),
      spectral analysis-derived parametric maps (3.6), and 2kbv (3.6). CONCLUSION:
      Quantification of CB1 receptor availability using [(11)C]MePPEP shows good to
      excellent reproducibility with several kinetic models and model-free analyses,
      whether applied on a region-of-interest or voxelwise basis. Simple mSUV measures
      were also reliable for most regions, but do not allow fully quantitative
      interpretation. [(11)C]MePPEP PET is well placed as a tool to investigate CB1
      receptor mediated neurotransmission in health and disease.

PMID- 24736186
TI  - Visual, auditory and tactile stimuli compete for early sensory processing
      capacities within but not between senses.
AB  - We investigated whether unattended visual, auditory and tactile stimuli compete
      for capacity-limited early sensory processing across senses. In three
      experiments, we probed competitive audio-visual, visuo-tactile and audio-tactile
      stimulus interactions. To this end, continuous visual, auditory and tactile
      stimulus streams ('reference' stimuli) were frequency-tagged to elicit steady
      state responses (SSRs). These electrophysiological oscillatory brain responses
      indexed ongoing stimulus processing in corresponding senses. To induce
      competition, we introduced transient frequency-tagged stimuli in same and/or
      different senses ('competitors') during reference presentation. Participants
      performed a separate visual discrimination task at central fixation to control
      for attentional biases of sensory processing. A comparison of reference-driven
      SSR amplitudes between competitor-present and competitor-absent periods revealed
      reduced amplitudes when a competitor was presented in the same sensory modality
      as the reference. Reduced amplitudes indicated the competitor's suppressive
      influence on reference stimulus processing. Crucially, no such suppression was
      found when a competitor was presented in a different than the reference modality.
      These results strongly suggest that early sensory competition is exclusively
      modality-specific and does not extend across senses. We discuss consequences of
      these findings for modeling the neural mechanisms underlying intermodal
      attention. 

PMID- 24736187
TI  - Selection and identification of single-domain antibody fragment against capsid
      protein of porcine circovirus type 2 (PCV2) from C. bactrianus.
AB  - Single-domain variable heavy chain (VHH) antibody fragments are derived from
      heavy-chain antibodies of Camelids. Their comparatively small size, solubility,
      high affinity and specificity to the targets antigen make them suitable for many
      biotechnological applications. In this study, a VHH library was constructed from
      porcine circovirus type 2 (PCV2) vaccine immunized C. bactrianus and three VHH
      fragments specific to the capsid protein of PCV2 (PCV2 Cap) were selected and
      characterized. The selected VHH clones (VHH-c1/c3/c4) were stably expressed as
      soluble protein in E. coli, and were specific to PCV2 Cap except VHH-c3 which
      shows binding activity with both PCV1 and PCV2 Cap by ELISA. All the VHH-cs show
      high association rate constant and dissociation rate constant, which was 1.84 *
      10(5)M(-1)s(-1), 9.00 * 10(-3)s(-1) for VHH-c1, 5.49 * 10(4)M(-1)s(-1), 9.91 *
      10(-3)s(-1) and 1.46 * 10(5)M(-1)s(-1), 1.18 * 10(-3)s(-1) for VHH-c3 and VHH-c4
      assessed by surface plasmon resonance (SPR). Additionally, the selected three VHH
      cs can bind to different epitopes of PCV2 Cap that was determined by additive
      ELISA. Our study confirmed that VHHs with high affinity and specificity to PCV2
      Cap can be selected from an immune VHH library, and have the potential
      application for effective and fast diagnostic development of PCV2.

PMID- 24736188
TI  - Effects of age and macrophage lineage on intracellular survival and cytokine
      induction after infection with Rhodococcus equi.
AB  - Rhodococcus equi, a facultative intracellular pathogen of macrophages, causes
      life-threatening pneumonia in foals and in people with underlying immune
      deficiencies. As a basis for this study, we hypothesized that macrophage lineage
      and age would affect intracellular survival of R. equi and cytokine induction
      after infection. Monocyte-derived and bronchoalveolar macrophages from 10 adult
      horses and from 10 foals (sampled at 1-3 days, 2 weeks, 1 month, 3 months, and 5
      months of age) were infected ex vivo with virulent R. equi. Intracellular R. equi
      were quantified and mRNA expression of IL-1beta, IL-4, IL-6, IL-8, IL-10, IL-12
      p40, IL-18, IFN-gamma, and TNF-alpha was measured. Intracellular replication of
      R. equi was significantly (P<0.001) greater in bronchoalveolar than in monocyte
      derived macrophages, regardless of age. Regardless of the macrophage lineage,
      replication of R. equi was significantly (P=0.002) higher in 3-month-old foals
      than in 3-day old foals, 2-week-old foals, 1-month-old foals, and adult horses.
      Expression of IL-4 mRNA was significantly higher in monocyte-derived macrophages
      whereas expression of IL-6, IL-18, and TNF-alpha was significantly higher in
      bronchoalveolar macrophages. Induction of IL-1beta, IL-10, IL-12 p40, and IL-8
      mRNA in bronchoalveolar macrophages of 1-3-day old foals was significantly higher
      than in older foals or adult horses. Preferential intracellular survival of R.
      equi in bronchoalveolar macrophages of juvenile horses may play a role in the
      pulmonary tropism of the pathogen and in the window of age susceptibility to
      infection. 

PMID- 24736189
TI  - Linear optimal control of continuous time chaotic systems.
AB  - In this research study, chaos control of continuous time systems has been
      performed by using dynamic programming technique. In the first step by crossing
      the response orbits with a selected Poincare section and subsequently applying
      linear regression method, the continuous time system is converted to a discrete
      type. Then, by solving the Riccati equation a sub-optimal algorithm has been
      devised for the obtained discrete chaotic systems. In the next step, by
      implementing the acquired algorithm on the quantized continuous time system, the
      chaos has been suppressed in the Rossler and AFM systems as some case studies. 

PMID- 24736190
TI  - The content of diet and physical activity consultations with older adults in
      primary care.
AB  - OBJECTIVE: Despite numerous benefits of consuming a healthy diet and receiving
      regular physical activity, engagement in these behaviors is suboptimal. Since
      primary care visits are influential in promoting healthy behaviors, we sought to
      describe whether and how diet and physical activity are discussed during older
      adults' primary care visits. METHODS: 115 adults aged 65 and older consented to
      have their routine primary care visits recorded. Audio-recorded visits were
      transcribed and diet and physical activity content was coded and analyzed.
      RESULTS: Diet and physical activity were discussed in the majority of visits.
      When these discussions occurred, they lasted an average of a minute and a half.
      Encouragement and broad discussion of benefits of improved diet and physical
      activity levels were the common type of exchange. Discussions rarely involved
      patient behavioral self-assessments, patient questions, or providers'
      recommendations. CONCLUSIONS: The majority of patient visits include discussion
      of diet and physical activity, but these discussions are often brief and rarely
      include recommendations. PRACTICE IMPLICATIONS: Providers may want to consider
      ways to expand their lifestyle behavior discussions to increase patient
      involvement and provide more detailed, actionable recommendations for behavior
      change. Additionally, given time constraints, a wider array of approaches to
      lifestyle counseling may be necessary.

PMID- 24736191
TI  - Spontaneous regression of an epidermoid cyst of the cavernous sinus.
AB  - Epidermoid cysts are rare lesions in the pediatric population. The natural
      history of epidermoids is usually that of slow growth, although rupture and cases
      of malignant transformation have been reported. Spontaneous regression of an
      intracranial epidermoid cyst has not previously been described to our knowledge.
      We present a 3-year-old boy who presented with severe vertigo. MRI was performed
      which revealed a 2cm non-enhancing lesion in the right cavernous sinus. The
      lesion was T1-hypoinsense, T2-hyperintense, and with evidence of restricted
      diffusion, consistent with an epidermoid cyst. The patient was followed with
      annual MRI studies over the next 3years, demonstrating progressive reduction in
      the size of the lesion over time, with complete resolution after 3years. The
      child's symptoms also resolved during this period. Long-term follow-up imaging at
      5years showed no evident lesion. To our knowledge, this is the first report
      documenting spontaneous regression of an intracranial epidermoid cyst. While
      isolated, this finding demonstrates the potential for involution of epidermoids
      and lends support to the clinical practice of careful observation of these
      lesions, especially when located in areas associated with high potential surgical
      morbidity. Importantly, the novelty of this observation suggests a need for
      further study to better elucidate the underlying mechanism of this regression. 

PMID- 24736192
TI  - Awake craniotomy and multilingualism: language testing during anaesthesia for
      awake craniotomy in a bilingual patient.
AB  - An awake craniotomy for epilepsy surgery is presented where a bilingual patient
      post-operatively reported temporary aphasia of his first language (Spanish). This
      case report discusses the potential causes for this clinical presentation and
      methods to prevent the occurrence of this in future patients undergoing this form
      of surgery. 

PMID- 24736193
TI  - Safety, efficacy, and cost of intraoperative indocyanine green angiography
      compared to intraoperative catheter angiography in cerebral aneurysm surgery.
AB  - Intraoperative angiography in cerebrovascular neurosurgery can drive the
      repositioning or addition of aneurysm clips. Our institution has switched from a
      strategy of intraoperative digital subtraction angiography (DSA) universally, to
      a strategy of indocyanine green (ICG) videoangiography with DSA on an as-needed
      basis. We retrospectively evaluated whether the rates of perioperative stroke,
      unexpected postoperative aneurysm residual, or parent vessel stenosis differed in
      100 patients from each era (2002, "DSA era"; 2007, "ICG era"). The clip
      repositioning rate for neck residual or parent vessel stenosis did not differ
      significantly between the two eras. There were no differences in the rate of
      perioperative stroke or rate of false-negative studies. The per-patient cost of
      intraoperative imaging within the DSA era was significantly higher than in the
      ICG era. The replacement of routine intraoperative DSA with ICG videoangiography
      and selective intraoperative DSA in cerebrovascular aneurysm surgery is safe and
      effective. 

PMID- 24736194
TI  - Rapidly progressive cognitive impairment in a patient with high flow dural
      arteriovenous fistulas, cerebral sinus thrombosis and protein S deficiency.
AB  - Dural arteriovenous fistula (DAVF) may present with a variety of neurological
      symptoms, ranging from tinnitus to fatal hemorrhage. We report a case of rapidly
      progressive cognitive impairment due to cerebral venous engorgement that reversed
      after endovascular treatment in a patient with DAVF, cerebral sinus thrombosis
      and protein S deficiency. DAVF may be a cause of vascular cognitive impairment
      and should be considered particularly in cases with a rapidly progressive course
      because they are potentially treatable. 

PMID- 24736195
TI  - Primary herpes virus infection and ischemic stroke in childhood: a new
      association?
AB  - We describe, to our knowledge, the first case of arterial ischemic stroke after
      primary herpes simplex virus type 1 (HSV1) infection in a previously healthy
      child, without signs of encephalitis. A 10-year-old previously healthy girl was
      admitted to our hospital with acute left-sided hemiparesis which involved the
      lower half of her face. Submandibular lymphadenitis and oral vesicular lesions
      were present. MRI confirmed the suspicion of an acute ischemic stroke.
      Immunoglobulin M antibodies to HSV1 were detected. Cerebrospinal fluid polymerase
      chain reaction for herpes virus was negative. She was treated with aspirin
      (3mg/kg) and intravenous acyclovir (10mg/kg every 8 hours) for 21 days.
      Immunoglobulin G antibodies to HSV1 appeared 16 days after admission. Twelve
      months after her hospitalization the patient's examination was normal. Stroke
      should be considered a possible complication of HSV1 primary infection.
      Guidelines for the management of acute stroke in children are needed.

PMID- 24736196
TI  - Knowledge and personal use of menopausal hormone therapy among Chinese
      obstetrician-gynecologists: results of a survey.
AB  - OBJECTIVE: Obstetrician-gynecologists' (ob-gyns) knowledge of the benefits and
      risks of-and attitude toward-menopausal hormone therapy (HT) have evolved since
      the publication of the Heart and Estrogen/progestin Replacement Study and the
      Women's Health Initiative. The survey investigated Chinese ob-gyns' perception
      and personal use of-and attitude toward-HT. METHODS: A total of 2,000 self
      administered questionnaires were sent to female ob-gyns who attended
      gynecological endocrinology workshops in 15 provinces and cities in China from
      February to May 2013. RESULTS: A total of 904 eligible questionnaires were
      collected (response rate, 45.2%). Most of the respondents knew that HT could
      relieve menopausal symptoms (97.7%) and prevent osteoporosis (93.5%). Most
      (69.4%) of the respondents thought that HT would increase the risk of breast
      cancer, and 52.9% thought that HT would increase the risk of endometrial cancer.
      The most common concern regarding adverse effects of HT was risk of breast
      cancer, followed by risk of endometrial cancer, risk of venous thrombosis, and
      weight gain. One hundred twenty-three of 324 symptomatic respondents (38.0%)
      reported HT use, and a further 28 respondents (8.6%) had tried transdermal and
      vaginal estrogen creams. CONCLUSIONS: These findings show better knowledge of HT
      among Chinese ob-gyns compared with the general Chinese population. However, HT
      use is relatively low, and ob-gyns seem to be overconcerned with the risks of HT.
      HT education must be promoted among Chinese ob-gyns to enhance the proper use of
      HT in the general population.

PMID- 24736197
TI  - Dietary phosphorus exacerbates bone loss induced by cadmium in ovariectomized
      rats.
AB  - OBJECTIVE: Postmenopausal bone loss can be exacerbated by environmental
      contaminants, including the heavy metal cadmium (Cd). We hypothesized that
      incorporating phosphorus (P) into the diet would lead to the chelation of Cd into
      P, preventing its absorption and subsequent bone loss. METHODS: To test this
      hypothesis, we used ovariectomized rats as a model of postmenopausal osteoporosis
      to examine the deleterious effects of Cd on bone with and without added P. Fifty
      3-month-old ovariectomized Sprague-Dawley rats were assigned to five treatment
      groups (n = 10 per group) for 3 months as follows: (1) control; (2) 50 ppm Cd;
      (3) 50 ppm Cd plus 1.2% P; (4) 200 ppm Cd; and (5) 200 ppm Cd plus 1.2% P.
      RESULTS: Cd plus P caused a significant loss of whole body (P = 0.0001 and P <
      0.001) and femoral (P = 0.0005 and P < 0.001) bone mineral density (BMD) and bone
      mineral content, respectively, and a loss of fourth lumbar vertebra BMD and bone
      mineral content (P < 0.0001 and P < 0.001, respectively). Nonetheless, 200 ppm Cd
      plus 1.2% P had the most deleterious effects on whole body and femoral BMD. For
      femoral neck microstructural properties, 50 ppm Cd plus 1.2% P caused an increase
      in trabecular separation, whereas 200 ppm Cd plus 1.2% P caused a decrease in
      bone volume-to-total volume ratio, a decrease in trabecular number, and an
      increase in trabecular separation and structural model index. CONCLUSIONS: Our
      findings indicate that Cd exposure, along with high intake of P, may be a public
      health hazard with respect to bone health.

PMID- 24736198
TI  - Lack of confidence intervals.

PMID- 24736199
TI  - Staging reproductive aging using Stages of Reproductive Aging Workshop + 10 in
      black urban African women in the Study of Women Entering and in Endocrine
      Transition.
AB  - OBJECTIVE: There has been limited research on accurate staging of the menopausal
      transition in sub-Saharan African women. Our aim was to assess the usefulness of
      the Stages of Reproductive Aging Workshop + 10 (STRAW + 10) criteria in staging
      ovarian aging in black South African women, examining whether obesity has any
      effect on the menopausal transition. METHODS: The study enrolled 702 women aged
      40 to 60 years. STRAW + 10 criteria were used to categorize the stages of
      reproductive aging. The Menopause Rating Scale was used to measure the prevalence
      of vasomotor symptoms. Follicle-stimulating hormone (FSH) and estradiol levels
      were used as supportive criteria for staging. Human immunodeficiency virus status
      was assessed using a point-of-care method. RESULTS: Reported age at final
      menstrual period (FMP) was higher in women interviewed within 4 years of FMP
      (mean [SD], 49.0 [3.80] y) than in women interviewed 10 years or more after FMP
      (mean [SD], 42.0 [4.06] y; P < 0.0005). In women within 4 years of FMP, lower
      body mass index was associated with earlier age at FMP. FSH levels increased and
      estradiol levels decreased (P < 0.0005 for both trends) across seven staging
      groups. Human immunodeficiency virus status had no effect on menopause symptoms.
      Obesity (body mass index >=35.0 kg/m) was associated with severe vasomotor
      symptoms. CONCLUSIONS: Reporting of age at FMP is unreliable in women interviewed
      4 years or more after the event. STRAW + 10 seems accurate in staging
      reproductive aging, as confirmed by the strong association of FSH and estradiol
      levels with the menopausal transition stage. STRAW + 10 may be appropriate for
      use in resource-limited settings in the absence of biomarkers. Biocultural
      methods may be useful in assessing the menopausal transition in culturally
      diverse women.

PMID- 24736201
TI  - In reply.

PMID- 24736200
TI  - Vitamin D levels and menopause-related symptoms.
AB  - OBJECTIVE: This study aims to determine whether vitamin D levels are associated
      with menopause-related symptoms in older women. METHODS: A randomly selected
      subset of 1,407 women, among 26,104 potentially eligible participants of the
      Women's Health Initiative Calcium and Vitamin D trial of postmenopausal women
      aged 51 to 80 years, had 25-hydroxyvitamin D [25(OH)D] levels measured at the
      Women's Health Initiative Calcium and Vitamin D trial baseline visit. Information
      about menopause-related symptoms at baseline was obtained by questionnaire and
      included overall number of symptoms and composite measures of sleep disturbance,
      emotional well-being, and energy/fatigue, as well as individual symptoms. After
      exclusions for missing data, 530 women (mean [SD] age, 66.2 [6.8] y) were
      included in these analyses. RESULTS: Borderline significant associations between
      25(OH)D levels and total number of menopausal symptoms were observed (with P
      values ranging from 0.05 to 0.06 for fully adjusted models); however, the effect
      was clinically insignificant and disappeared with correction for multiple
      testing. No associations between 25(OH)D levels and composite measures of sleep
      disturbance, emotional well-being, or energy/fatigue were observed (P's > 0.10
      for fully adjusted models). CONCLUSIONS: There is no evidence for a clinically
      important association between serum 25(OH)D levels and menopause-related symptoms
      in postmenopausal women.

PMID- 24736202
TI  - Coverage planning in computer-assisted ablation based on Genetic Algorithm.
AB  - An ablation planning system plays a pivotal role in tumor ablation procedures, as
      it provides a dry run to guide the surgeons in a complicated anatomical
      environment. Over-ablation, over-perforation or under-ablation may result in
      complications during the treatments. An optimal solution is desired to have
      complete tumor coverage with minimal invasiveness, including minimal number of
      ablations and minimal number of perforation trajectories. As the planning of
      tumor ablation is a multi-objective problem, it is challenging to obtain optimal
      covering solutions based on clinician's experiences. Meanwhile, it is effective
      for computer-assisted systems to decide a set of optimal plans. This paper
      proposes a novel approach of integrating a computational optimization algorithm
      into the ablation planning system. The proposed ablation planning system is
      designed based on the following objectives: to achieve complete tumor coverage
      and to minimize the number of ablations, number of needle trajectories and over
      ablation to the healthy tissue. These objectives are taken into account using a
      Genetic Algorithm, which is capable of generating feasible solutions within a
      constrained search space. The candidate ablation plans can be encoded in
      generations of chromosomes, which subsequently evolve based on a fitness
      function. In this paper, an exponential weight-criterion fitness function has
      been designed by incorporating constraint parameters that were reflective of the
      different objectives. According to the test results, the proposed planner is able
      to generate the set of optimal solutions for tumor ablation problem, thereby
      fulfilling the aforementioned multiple objectives. 

PMID- 24736203
TI  - Breast cancer detection from MR images through an auto-probing discrete Fourier
      transform system.
AB  - A computer-aided detection auto-probing (CADAP) system is presented for detecting
      breast lesions using dynamic contrast enhanced magnetic resonance imaging,
      through a spatial-based discrete Fourier transform. The stand-alone CADAP system
      reduces noise, refines region of interest (ROI) automatically, and detects the
      breast lesion with minimal false positive detection. The lesions are then
      classified and colourised according to their characteristics, whether benign,
      suspicious or malignant. To enhance the visualisation, the entire analysed ROI is
      constructed into a 3-D image, so that the user can diagnose based on multiple
      views on the ROI. The proposed method has been applied to 101 sets of digital
      images, and the results compared with the biopsy results done by radiologists.
      The proposed scheme is able to identify breast cancer regions accurately and
      efficiently. 

PMID- 24736204
TI  - Identification and characterization of a QM protein as a possible peptidoglycan
      recognition protein (PGRP) from the giant tiger shrimp Penaeus monodon.
AB  - In an attempt to identify a peptidoglycan recognition protein (PGRP) in Penaeus
      (Penaeus) monodon, in vitro pull-down binding assays were used between shrimp
      proteins and purified peptidoglycan (PG). By gel electrophoresis and mass
      spectrometry followed by Mascot program analysis, proteins from shrimp hemocyte
      peripheral membrane proteins showed significant homology to records for a QM
      protein, actin and prophenoloxidase 2 precursor (proPO2), while proteins from
      cell-free plasma showed significant homology to records for a vitellogenin, a
      fibrinogen related protein (FREP) and a C-type lectin. Due to time and resource
      limitations, specific binding to PG was examined only for recombinant PmQM
      protein and PmLec that were synthesized based on sequences reported in the
      Genbank database (accession numbers FJ766846 and DQ078266, respectively). An in
      vitro assay revealed that hemocytes would bind with and encapsulate agarose beads
      coated with recombinant PmQM (rPmQM) or rPmLec and that melanization followed 2h
      post-encapsulation. ELISA tests confirmed specific binding of rPmQM protein to
      PG. This is the first time that PmQM has been reported as a potential PGRP in
      shrimp or any other crustacean. The two other potential PGRP identified (FREP and
      the vitellin-like protein present in male P. monodon, unlike other vitellin
      subunits) should also be expressed heterologously and tested for their ability to
      activate shrimp hemocytes. 

PMID- 24736205
TI  - Effects of TLR agonists and viral infection on cytokine and TLR expression in
      Atlantic salmon (Salmo salar).
AB  - The development of efficient and cheap vaccines against several aquatic viruses
      is necessary for a sustainable fish farming industry. Toll-like receptor (TLR)
      ligands have already been used as good adjuvants in human vaccines. With more
      understanding of TLR expression, function, and ligand specificity in fish, more
      efficient adjuvants for fish viral vaccines can be developed. In this paper, we
      examine all known TLRs in Atlantic salmon (Salmo salar) and demonstrate that head
      kidney and spleen are the main organs expressing TLRs in salmon. We also show
      that adherent head kidney leucocytes from salmon are able to respond to many of
      the known agonists for human TLRs, and that viral infection can induce up
      regulation of several TLRs. These findings substantiate these receptors' role in
      immune responses to pathogens in salmonids making their ligands attractive as
      vaccine adjuvant candidates. 

PMID- 24736207
TI  - Effect of solids retention time on the bioavailability of organic carbon in
      anaerobically digested swine waste.
AB  - Anaerobic digestion (AD) can be used to stabilize and produce energy from
      livestock waste; however, digester effluents may require further treatment to
      remove nitrogen. This paper quantifies the effects of varying solids retention
      time (SRT) methane yield, volatile solids (VS) reduction and organic carbon
      bioavailability for denitrification during swine waste AD. Four bench-scale
      anaerobic digesters, with SRTs of 14, 21, 28 and 42 days, operated with swine
      waste feed. Effluent organic carbon bioavailability was measured using anoxic
      microcosms and respirometry. Excellent performance was observed for all four
      digesters, with >60% VS removal and CH4 yields between 0.1 and 0.3(m(3)CH4)/(kg
      VS added). Organic carbon in the centrate as an internal organic carbon source
      for denitrification supported maximum specific denitrification rates between 47
      and 56(mg NO3(-)-N)/(g VSS h). The digester with the 21-day SRT had the highest
      CH4 yield and maximum specific denitrification rates.

PMID- 24736208
TI  - Co-gasification of biomass and plastics: pyrolysis kinetics studies, experiments
      on 100 kW dual fluidized bed pilot plant and development of thermodynamic
      equilibrium model and balances.
AB  - Thermo-gravimetric analysis (TGA) of volatilization reaction kinetics for 50 wt.%
      mixtures of plastics (PE) and biomass (wood pellets) as well as for 100 wt.%
      plastics was conducted to predict decomposition times at 850 degrees C and 900
      degrees C using iso-conversional model method. For mixtures, agreement with
      residence time of dual fluidized bed (DFB) reactor, treated as continuous stirred
      tank reactor (CSTR), was obtained at large conversions. Mono-gasification of
      plastics and its co-gasification with biomass were performed in DFB pilot plant,
      using olivine as heterogeneous catalyst and heat transfer agent. It was found
      that co-gasification led to successful thermochemical conversion of plastics as
      opposed to mono-gasification. Unknown flow rates were determined applying
      nonlinear regression to energy and mass balances acknowledging combustion fuel,
      air, steam, feedstock, but also exiting char, tar, steam and other components in
      DFB gasification unit. Water-gas shift equilibrium and methanol synthesis
      requirements were incorporated into gasification model, based on measurements.

PMID- 24736209
TI  - Population dynamics of nitrifying bacteria for nitritation achieved in
      Johannesburg (JHB) process treating municipal wastewater.
AB  - Population dynamic of nitrifying bacteria was investigated for nitrogen removal
      from municipal wastewater. Nitritation was established with nitrite accumulation
      ratios above 85%. Quantitative PCR indicated that Nitrospira was dominant nitrite
      oxidizing bacteria (NOB) and Nitrobacter was few. During nitritation achieving,
      Nitrobacter was firstly eliminated, along with inhibition of Nitrospira
      bioactivities, then Nitrospira percentage declined and was finally washed out.
      Nitritation establishment depended on inhibiting and eliminating of NOB rather
      than ammonia oxidizing bacteria (AOB) enriching. This is the first study where
      population dynamics of Nitrobacter and Nitrospira were investigated to reveal
      mechanism of nitritation in a continuous-flow process. Phylogenetic analysis of
      AOB indicated that Nitrosomonas-like cluster and Nitrosomonas oligotropha were
      dominant AOB, accounting for 81.6% of amoA gene clone library. Community
      structure of AOB was similar to that of complete nitrification system with long
      hydraulic retention time, but different from that of nitritation reactor with low
      DO concentration. 

PMID- 24736210
TI  - Enhancing growth and lipid production of marine microalgae for biodiesel
      production via the use of different LED wavelengths.
AB  - Wavelength of light is a crucial factor which renders microalgae as the potential
      biodiesel. In this study, Tetraselmis sp. and Nannochloropsis sp. as famous
      targets were selected. The effect of different light wavelengths on growth rate
      and lipid production was studied. Microalgae were cultivated for 14 days as under
      blue, red, red-blue LED and white fluorescent light. The growth rate of
      microalgae was analyzed by spectrophotometer and cell counting while oil
      production under improved Nile red method. Optical density result showed the
      microalgae exhibited better growth curve under blue wavelength. Besides,
      Tetraselmis sp. and Nannochloropsis sp. under blue wavelength showed the higher
      growth rate (1.47 and 1.64 day(-1)) and oil production (102.954 and 702.366
      a.u.). Gas chromatography analysis also showed that palmitic acid and stearic
      acid which were compulsory components for biodiesel contribute around 49-51% of
      total FAME from Nannochloropsis sp. and 81-83% of total FAME from Tetraselmis sp.

PMID- 24736211
TI  - Induction of a laccase Lcc9 from Coprinopsis cinerea by fungal coculture and its
      application on indigo dye decolorization.
AB  - A fungal coculture system comprised of Coprinopsis cinerea Okayama 7 (#130) and
      Gongronella sp. w5 produced 900 times higher laccase activity than that in pure
      culture. A fungal laccase named Lcc9 was induced from C. cinerea for the first
      time by coculture. Lcc9 was purified, characterized, and found to have high
      activity toward phenolic substrates at the optimum pH of 6.5 and temperature of
      60 degrees C. The laccase was stable at alkaline pH values, and its activity was
      not significantly affected by cations and organic solvents. Lcc9 showed
      decolorization capability toward indigo dye in the presence of 2,2'-azino-bis(3
      ethylbenzothazoline-6-sulfonate), with 75% of indigo was decolorized by 50 U/L
      enzyme after 1h of incubation under optimal catalytic conditions. These results
      showed that fungal coculture could active silent laccase gene, and the unusual
      properties make Lcc9 a candidate for specific industrial and environmental
      applications.

PMID- 24736206
TI  - Global, regional, and national consumption levels of dietary fats and oils in
      1990 and 2010: a systematic analysis including 266 country-specific nutrition
      surveys.
AB  - OBJECTIVES: To quantify global consumption of key dietary fats and oils by
      country, age, and sex in 1990 and 2010. DESIGN: Data were identified, obtained,
      and assessed among adults in 16 age- and sex-specific groups from dietary surveys
      worldwide on saturated, omega 6, seafood omega 3, plant omega 3, and trans fats,
      and dietary cholesterol. We included 266 surveys in adults (83% nationally
      representative) comprising 1,630,069 unique individuals, representing 113 of 187
      countries and 82% of the global population. A multilevel hierarchical Bayesian
      model accounted for differences in national and regional levels of missing data,
      measurement incomparability, study representativeness, and sampling and modelling
      uncertainty. SETTING AND POPULATION: Global adult population, by age, sex,
      country, and time. RESULTS: In 2010, global saturated fat consumption was 9.4%E
      (95%UI=9.2 to 9.5); country-specific intakes varied dramatically from 2.3 to
      27.5%E; in 75 of 187 countries representing 61.8% of the world's adult
      population, the mean intake was <10%E. Country-specific omega 6 consumption
      ranged from 1.2 to 12.5%E (global mean=5.9%E); corresponding range was 0.2 to
      6.5%E (1.4%E) for trans fat; 97 to 440 mg/day (228 mg/day) for dietary
      cholesterol; 5 to 3,886 mg/day (163 mg/day) for seafood omega 3; and <100 to
      5,542 mg/day (1,371 mg/day) for plant omega 3. Countries representing 52.4% of
      the global population had national mean intakes for omega 6 fat >= 5%E;
      corresponding proportions meeting optimal intakes were 0.6% for trans fat (<=
      0.5%E); 87.6% for dietary cholesterol (<300 mg/day); 18.9% for seafood omega 3
      fat (>= 250 mg/day); and 43.9% for plant omega 3 fat (>= 1,100 mg/day). Trans fat
      intakes were generally higher at younger ages; and dietary cholesterol and
      seafood omega 3 fats generally higher at older ages. Intakes were similar by sex.
      Between 1990 and 2010, global saturated fat, dietary cholesterol, and trans fat
      intakes remained stable, while omega 6, seafood omega 3, and plant omega 3 fat
      intakes each increased. CONCLUSIONS: These novel global data on dietary fats and
      oils identify dramatic diversity across nations and inform policies and
      priorities for improving global health.

PMID- 24736212
TI  - Therapeutic targeting of naturally presented myeloperoxidase-derived HLA peptide
      ligands on myeloid leukemia cells by TCR-transgenic T cells.
AB  - T cells have been proven to be therapeutically effective in patients with
      relapsed leukemias, although target antigens on leukemic cells as well as T-cell
      receptors (TCRs), potentially recognizing those antigens, are mostly unknown. We
      have applied an immunopeptidomic approach and isolated human leukocyte antigen
      (HLA) ligands from primary leukemia cells. We identified a number of ligands
      derived from different genes that are restrictedly expressed in the hematopoietic
      system. We exemplarily selected myeloperoxidase (MPO) as a potential target and
      isolated a high-avidity TCR with specificity for a HLA-B*07:02-(HLA-B7)
      restricted epitope of MPO in the single HLA-mismatched setting. T cells
      transgenic for this TCR demonstrated high peptide and antigen specificity as well
      as leukemia reactivity in vitro and in vivo. In contrast, no significant on- and
      off-target toxicity could be observed. In conclusion, we here demonstrate,
      exemplarily for MPO, that leukemia-derived HLA ligands can be selected for
      specific effector tool development to redirect T cells to be used for graft
      manipulation or adoptive T-cell therapies in diverse transplant settings. This
      approach can be extended to other HLA ligands and HLA molecules in order to
      provide better treatment options for this life-threatening disease. 

PMID- 24736213
TI  - TSP1-producing B cells show immune regulatory property and suppress allergy
      related mucosal inflammation.
AB  - Specific immunotherapy (SIT) is the only specific remedy for the treatment of
      allergic diseases currently. B cells are important immune cells in the immunity.
      The role of B cells in immune regulatory activities has not been fully understood
      yet. This study aims to elucidate the role of the thrombospondin (TSP)1-producing
      B cells in the immune regulatory role of SIT. The results showed that after SIT,
      the frequency of CD35(+) B cells was increased in the intestine of mice with food
      allergy. The CD35(+) B cells expressed TSP1 after exposure to specific antigens.
      Co-culture with the TSP1-producing CD35(+) B cells decreased the levels of
      CD80/CD86 in dendritic cells; the cells convert naive CD4(+) T cells to
      regulatory T cells to inhibit allergic inflammation in the intestine. 

PMID- 24736214
TI  - Muju virus, harbored by Myodes regulus in Korea, might represent a genetic
      variant of Puumala virus, the prototype arvicolid rodent-borne hantavirus.
AB  - The genome of Muju virus (MUJV), identified originally in the royal vole (Myodes
      regulus) in Korea, was fully sequenced to ascertain its genetic and phylogenetic
      relationship with Puumala virus (PUUV), harbored by the bank vole (My.
      glareolus), and a PUUV-like virus, named Hokkaido virus (HOKV), in the grey red
      backed vole (My. rufocanus) in Japan. Whole genome sequence analysis of the 6544
      nucleotide large (L), 3652-nucleotide medium (M) and 1831-nucleotide small (S)
      segments of MUJV, as well as the amino acid sequences of their gene products,
      indicated that MUJV strains from different capture sites might represent genetic
      variants of PUUV, the prototype arvicolid rodent-borne hantavirus in Europe.
      Distinct geographic-specific clustering of MUJV was found in different provinces
      in Korea, and phylogenetic analyses revealed that MUJV and HOKV share a common
      ancestry with PUUV. A better understanding of the taxonomic classification and
      pathogenic potential of MUJV must await its isolation in cell culture. 

PMID- 24736216
TI  - [French tropical medicine and international cooperation. Issues and
      perspectives].

PMID- 24736217
TI  - [Impact of excessive weight gain during pregnancy on maternal and fetal outcome
      at the Yaounde Women's and Children's Hospital (Cameroon)].
AB  - Excessive weight gain (EWG) during pregnancy can cause maternal and fetal
      complications. It has not yet been studied in our social environment, however.
      OBJECTIVES: Our study aimed to describe maternal and fetal outcome in women
      gaining excessive weight during pregnancy in Cameroon. METHODOLOGY: This cross
      sectional descriptive study took place over a two-month period. Women were
      interviewed after delivery and grouped in two categories: those who did and did
      not have EWG during pregnancy. The complications due to EWG were analyzed.
      RESULTS: The frequency of EWG in pregnancy was 35.5%. The incidence of high blood
      pressure was 9.8% for patients with EWG, and 6% for those with normal weight
      gains (P = 0.301). The mean birth weight of the babies of women with EWG was
      3,433 g, significantly higher than the 3,103.7 g (P = 0.001) of the babies in the
      other group. Patients with EWG had significantly fewer babies with low birth
      weight (P<0.05) and significantly more with macrosomia (P<0.01). The cesarean
      rate was higher, but not significantly so, for women with EWG (23.2% vs 16.1%, P
      = 0.187); this was the case as well for postpartum hemorrhage and (1- and 5-min)
      Apgar scores as well. CONCLUSION: EWG is associated with a higher incidence of
      macrosomia, but does not significantly increase the rate of cesarean births or
      modify the Apgar scores.

PMID- 24736218
TI  - [Stevens-Johnson syndrome and toxic epidermal necrolysis: retrospective study of
      185 cases in Abidjan (Cote d'Ivoire)].
AB  - BACKGROUND: Cutaneous bullous adverse drug eruptions are a dreaded complication
      of drug use. OBJECTIVE: The purpose of this study was to document the
      epidemiological features, outcomes, and causes of these reactions, in particular,
      Stevens-Johnson syndrome and toxic epidermal necrolysis (Lyell disease), in a
      teaching hospital in Abidjan (Cote d'Ivoire). PATIENTS AND METHODS: A
      retrospective study reviewed the records of severe cutaneous drug reactions in
      patients managed in the dermatology department of the University Hospital of
      Treichville (Abidjan) over a period of ten years (from September 2000 through
      August 2010). RESULTS: These diseases were diagnosed in 185 patients during the
      study period. Their mean age was 31.8 years (range: 2-70 years) and the M/F sex
      ratio was 0.6 The most frequent reactions, as expected, were Stevens-Johnson
      syndrome (73%) and toxic epidermal necrolysis (27%). The drugs most commonly
      involved were the antibacterial sulfonamides (22.1%), followed by the antiviral
      nevirapine (11.1%), and the antimalarial agent, sulfadoxine/pyrimethamine. The
      fatality rate was 22.5%, including 46% of the patients with toxic epidermal
      necrolysis and 14.6% of those with Stevens-Johnson syndrome. Respiratory distress
      (39.5%) and dehydration (23.4%) were the primary direct causes of death.
      CONCLUSION: Antibacterial sulfonamides are the leading drugs implicated in the
      occurrence of bullous drug eruptions in Abidjan.

PMID- 24736219
TI  - [Noma in a 4 year-old girl: a case report from Chad].
AB  - This case report describes a 4-year-old girl in Chad with noma, also called
      cancrum oris. This acute gangrenous stomatitis has a combined morbidity-mortality
      rate that can reach 70%. It occurs worldwide but is most common in sub-Saharan
      Africa in children aged 2 to 16 years. Its pathogenesis is uncertain, but several
      bacteria including Fusobacterium necrophorum, Prevotella intermedia and
      Pseudomonas aeruginosa may be responsible for the development of noma, which
      develops over the oral lesions these bacteria cause. Poverty is its most
      important risk factor. Due to its rapid course and high lethality, it requires
      emergency treatment with antibiotics, daily dressing of the lesion, and
      nutritional rehabilitation. Surgical removal of the remaining necrotic tissue can
      be followed by reconstructive procedures. Physical and speech therapy should be
      initiated to prevent functional complications. 

PMID- 24736215
TI  - HIV-1 latency: an update of molecular mechanisms and therapeutic strategies.
AB  - The major obstacle towards HIV-1 eradication is the life-long persistence of the
      virus in reservoirs of latently infected cells. In these cells the proviral DNA
      is integrated in the host's genome but it does not actively replicate, becoming
      invisible to the host immune system and unaffected by existing antiviral drugs.
      Rebound of viremia and recovery of systemic infection that follows interruption
      of therapy, necessitates life-long treatments with problems of compliance,
      toxicity, and untenable costs, especially in developing countries where the
      infection hits worst. Extensive research efforts have led to the proposal and
      preliminary testing of several anti-latency compounds, however, overall,
      eradication strategies have had, so far, limited clinical success while posing
      several risks for patients. This review will briefly summarize the more recent
      advances in the elucidation of mechanisms that regulates the
      establishment/maintenance of latency and therapeutic strategies currently under
      evaluation in order to eradicate HIV persistence. 

PMID- 24736220
TI  - [Which antivenom for Cerastes envenoming?].
AB  - During Echis viper envenoming, the administration of a single FAV-Afrique((r))
      antivenin vial generally corrects hemostasis disorders in less than twelve hours.
      The correction of hemostasis after 36 hours by 4 vials of FAV-Afrique((r)) is
      thus not in favor of the usefulness of this antivenin for Cerastes envenoming .
      Mortality due to viper envenoming in Africa is high, but more than 90 % of
      poisoned patients survive despite the absence of appropriate antivenom. The
      severity of poisoning depends on several factors: age and condition of the
      patient, location of the bite, composition and amount of injected venom,
      management delay, and therefore, survival is not necessarily synonymous of
      effectiveness of antivenom treatment. Cerastes venoms contain many enzymes that
      disrupt various stages of hemostasis. It remains to prove that FAV-Afrique((r)),
      a polyvalent antivenom adapted to venom of the main species responsible for
      envenoming in sub-Saharan Africa, (Bitis, Echis, Naja and Dendroaspis), is able
      to neutralize these specific proteins. The most logical approach of Cerastes
      envenoming is the administration of an antivenin adapted to species found in
      North Africa: Favirept((r)) (Sanofi Pasteur) is a polyvalent antivenom adapted to
      the venoms of C. cerastes, Bitis arietans, Echis leucogaster, Macrovipera
      deserti, Naja haje and Naja nigricollis. 

PMID- 24736221
TI  - Burkholderia pseudomallei penetrates the brain via destruction of the olfactory
      and trigeminal nerves: implications for the pathogenesis of neurological
      melioidosis.
AB  - ABSTRACT Melioidosis is a potentially fatal disease that is endemic to tropical
      northern Australia and Southeast Asia, with a mortality rate of 14 to 50%. The
      bacterium Burkholderia pseudomallei is the causative agent which infects numerous
      parts of the human body, including the brain, which results in the neurological
      manifestation of melioidosis. The olfactory nerve constitutes a direct conduit
      from the nasal cavity into the brain, and we have previously reported that B.
      pseudomallei can colonize this nerve in mice. We have now investigated in detail
      the mechanism by which the bacteria penetrate the olfactory and trigeminal nerves
      within the nasal cavity and infect the brain. We found that the olfactory
      epithelium responded to intranasal B. pseudomallei infection by widespread
      crenellation followed by disintegration of the neuronal layer to expose the
      underlying basal layer, which the bacteria then colonized. With the loss of the
      neuronal cell bodies, olfactory axons also degenerated, and the bacteria then
      migrated through the now-open conduit of the olfactory nerves. Using
      immunohistochemistry, we demonstrated that B. pseudomallei migrated through the
      cribriform plate via the olfactory nerves to enter the outer layer of the
      olfactory bulb in the brain within 24 h. We also found that the bacteria
      colonized the thin respiratory epithelium in the nasal cavity and then rapidly
      migrated along the underlying trigeminal nerve to penetrate the cranial cavity.
      These results demonstrate that B. pseudomallei invasion of the nerves of the
      nasal cavity leads to direct infection of the brain and bypasses the blood-brain
      barrier. IMPORTANCE Melioidosis is a potentially fatal tropical disease that is
      endemic to northern Australia and Southeast Asia. It is caused by the bacterium
      Burkholderia pseudomallei, which can infect many organs of the body, including
      the brain, and results in neurological symptoms. The pathway by which the
      bacteria can penetrate the brain is unknown, and we have investigated the ability
      of the bacteria to migrate along nerves that innervate the nasal cavity and enter
      the frontal region of the brain by using a mouse model of infection. By
      generating a mutant strain of B. pseudomallei which is unable to survive in the
      blood, we show that the bacteria rapidly penetrate the cranial cavity using the
      olfactory (smell) nerve and the trigeminal (sensory) nerve that line the nasal
      cavity.

PMID- 24736222
TI  - A new group of phage anti-CRISPR genes inhibits the type I-E CRISPR-Cas system of
      Pseudomonas aeruginosa.
AB  - CRISPR-Cas systems are one of the most widespread phage resistance mechanisms in
      prokaryotes. Our lab recently identified the first examples of phage-borne anti
      CRISPR genes that encode protein inhibitors of the type I-F CRISPR-Cas system of
      Pseudomonas aeruginosa. A key question arising from this work was whether there
      are other types of anti-CRISPR genes. In the current work, we address this
      question by demonstrating that some of the same phages carrying type I-F anti
      CRISPR genes also possess genes that mediate inhibition of the type I-E CRISPR
      Cas system of P. aeruginosa. We have discovered four distinct families of these
      type I-E anti-CRISPR genes. These genes do not inhibit the type I-F CRISPR-Cas
      system of P. aeruginosa or the type I-E system of Escherichia coli. Type I-E and
      I-F anti-CRISPR genes are located at the same position in the genomes of a large
      group of related P. aeruginosa phages, yet they are found in a variety of
      combinations and arrangements. We have also identified functional anti-CRISPR
      genes within nonprophage Pseudomonas genomic regions that are likely mobile
      genetic elements. This work emphasizes the potential importance of anti-CRISPR
      genes in phage evolution and lateral gene transfer and supports the hypothesis
      that more undiscovered families of anti-CRISPR genes exist. Finally, we provide
      the first demonstration that the type I-E CRISPR-Cas system of P. aeruginosa is
      naturally active without genetic manipulation, which contrasts with E. coli and
      other previously characterized I-E systems. IMPORTANCE The CRISPR-Cas system is
      an adaptive immune system possessed by the majority of prokaryotic organisms to
      combat potentially harmful foreign genetic elements. This study reports the
      discovery of bacteriophage-encoded anti-CRISPR genes that mediate inhibition of a
      well-studied subtype of CRISPR-Cas system. The four families of anti-CRISPR genes
      described here, which comprise only the second group of anti-CRISPR genes to be
      identified, encode small proteins that bear no sequence similarity to previously
      studied phage or bacterial proteins. Anti-CRISPR genes represent a newly
      discovered and intriguing facet of the ongoing evolutionary competition between
      phages and their bacterial hosts.

PMID- 24736223
TI  - O-mannosylation in Candida albicans enables development of interkingdom biofilm
      communities.
AB  - Candida albicans is a fungus that colonizes oral cavity surfaces, the gut, and
      the genital tract. Streptococcus gordonii is a ubiquitous oral bacterium that has
      been shown to form biofilm communities with C. albicans. Formation of dual
      species S. gordonii-C. albicans biofilm communities involves interaction of the
      S. gordonii SspB protein with the Als3 protein on the hyphal filament surface of
      C. albicans. Mannoproteins comprise a major component of the C. albicans cell
      wall, and in this study we sought to determine if mannosylation in cell wall
      biogenesis of C. albicans was necessary for hyphal adhesin functions associated
      with interkingdom biofilm development. A C. albicans mnt1Delta mnt2Delta mutant,
      with deleted alpha-1,2-mannosyltransferase genes and thus defective in O
      mannosylation, was abrogated in biofilm formation under various growth conditions
      and produced hyphal filaments that were not recognized by S. gordonii. Cell wall
      proteomes of hypha-forming mnt1Delta mnt2Delta mutant cells showed growth medium
      dependent alterations, compared to findings for the wild type, in a range of
      protein components, including Als1, Als3, Rbt1, Scw1, and Sap9. Hyphal filaments
      formed by mnt1Delta mnt2Delta mutant cells, unlike wild-type hyphae, did not
      interact with C. albicans Als3 or Hwp1 partner cell wall proteins or with S.
      gordonii SspB partner adhesin, suggesting defective functionality of adhesins on
      the mnt1Delta mnt2Delta mutant. These observations imply that early stage O
      mannosylation is critical for activation of hyphal adhesin functions required for
      biofilm formation, recognition by bacteria such as S. gordonii, and microbial
      community development. IMPORTANCE In the human mouth, microorganisms form
      communities known as biofilms that adhere to the surfaces present. Candida
      albicans is a fungus that is often found within these biofilms. We have focused
      on the mechanisms by which C. albicans becomes incorporated into communities
      containing bacteria, such as Streptococcus. We find that impairment of early
      stage addition of mannose sugars to C. albicans hyphal filament proteins
      deleteriously affects their subsequent performance in mediating formation of
      polymicrobial biofilms. Our analyses provide new understanding of the way that
      microbial communities develop, and of potential means to control C. albicans
      infections.

PMID- 24736224
TI  - In vitro and in vivo studies of a rapid and selective breath test for
      tuberculosis based upon mycobacterial CO dehydrogenase.
AB  - One of the major hurdles in treating tuberculosis (TB) is the time-consuming and
      difficult methodology for diagnosis. Stable-isotope breath tests hold great
      potential for rapidly diagnosing an infectious disease, monitoring therapy, and
      determining a bacterial phenotype in a rapid, point-of-care manner that does not
      require invasive sampling. Here we describe the preclinical development of a
      potentially highly selective TB diagnostic breath test based upon the organism's
      CO dehydrogenase activity. After development of the test in vitro, we were able
      to use the breath test to discriminate between infected and control rabbits,
      demonstrating that a diagnosis can potentially be made and also that a complex
      bacterial phenotype can be noninvasively and rapidly studied in the host.
      IMPORTANCE Tuberculosis (TB) remains a major infectious cause of disease and
      death worldwide, and effective diagnosis and then treatment are the tools with
      which we fight TB. The more quickly and more specific the diagnosis can be made,
      the better, and this is also true of diagnosis being as close to the patient
      (point of care) as possible. Here we report our preclinical development of breath
      tests based upon specific mycobacterial metabolism that could, with development,
      allow rapid point-of-care diagnosis through measuring the mycobacterial
      conversion of labeled CO to labeled CO2.

PMID- 24736225
TI  - Oxygen limitation within a bacterial aggregate.
AB  - ABSTRACT Cells within biofilms exhibit physiological heterogeneity, in part
      because of chemical gradients existing within these spatially structured
      communities. Previous work has examined how chemical gradients develop in large
      biofilms containing >10(8) cells. However, many bacterial communities in nature
      are composed of small, densely packed aggregates of cells (<= 10(5) bacteria).
      Using a gelatin-based three-dimensional (3D) printing strategy, we confined the
      bacterium Pseudomonas aeruginosa within picoliter-sized 3D "microtraps" that are
      permeable to nutrients, waste products, and other bioactive small molecules. We
      show that as a single bacterium grows into a maximally dense (10(12) cells ml(
      1)) clonal population, a localized depletion of oxygen develops when it reaches a
      critical aggregate size of ~55 pl. Collectively, these data demonstrate that
      chemical and phenotypic heterogeneity exists on the micrometer scale within small
      aggregate populations. IMPORTANCE Before developing into large, complex
      communities, microbes initially cluster into aggregates, and it is unclear if
      chemical heterogeneity exists in these ubiquitous micrometer-scale aggregates. We
      chose to examine oxygen availability within an aggregate since oxygen
      concentration impacts a number of important bacterial processes, including
      metabolism, social behaviors, virulence, and antibiotic resistance. By
      determining that oxygen availability can vary within aggregates containing <=
      10(5) bacteria, we establish that physiological heterogeneity exists within P.
      aeruginosa aggregates, suggesting that such heterogeneity frequently exists in
      many naturally occurring small populations.

PMID- 24736226
TI  - Vaccine-induced measles virus-specific T cells do not prevent infection or
      disease but facilitate subsequent clearance of viral RNA.
AB  - Infection with wild-type measles virus (MeV) induces lifelong protection from
      reinfection, and parenteral delivery of the live attenuated measles vaccine (LAV)
      also provides protection from measles. The level of neutralizing antibody is a
      good indicator of protection, but the independent roles of MeV-specific antibody
      and T cells have not been identified. In this study, macaques immunized with LAV
      through a nebulizer and a mouthpiece developed MeV-specific T-cell responses but
      not neutralizing antibodies. Upon challenge with wild-type MeV, these animals
      developed rashes and viremias similar to those in naive animals but cleared viral
      RNA from blood 25 to 40 days faster. The nebulizer-immunized animals also had
      more robust MeV-specific CD4(+) and CD8(+) T-cell responses than the naive
      animals after challenge, characterized by a higher number and better durability
      of gamma interferon (IFN-gamma)-producing cells. Induction of MeV-specific
      circulating CD4(+) and CD8(+) T cells capable of producing multiple cytokines
      correlated with clearance of viral RNA in the nebulizer-immunized macaques. These
      studies demonstrated that MeV-specific T-cell immunity alone did not prevent
      measles, but T-cell priming enhanced the magnitude, durability, and
      polyfunctionality of MeV-specific T cells after challenge infection and
      correlated with more rapid clearance of MeV RNA. IMPORTANCE The components of
      vaccine-induced immunity necessary for protection from infection and disease have
      not been clearly identified for most vaccines. Vaccine development usually
      focuses on induction of antibody, but T-cell-based vaccines are also under
      development. The live attenuated measles vaccine (LAV) given subcutaneously
      induces both T cells and neutralizing antibody and provides solid protection from
      infection. LAV delivered to the upper respiratory tract through a nebulizer and
      mouthpiece induced a T-cell response but no neutralizing antibody. These T-cell
      primed macaques demonstrated no protection from rash or viremia when challenged
      with wild-type MeV, but viral RNA was cleared more rapidly than in unimmunized
      animals. Thus, T-cell immunity did not protect from infection or acute disease
      but facilitated virus clearance during recovery. These studies demonstrate the
      importance and independent roles of T cells and antibody in protection and
      recovery from measles.

PMID- 24736227
TI  - Production and characterization of a monoclonal antibody against recombinant
      cathepsin L1 of Fasciola gigantica.
AB  - Monoclonal antibodies (MoAbs) against a recombinant cathepsin L1 of Fasciola
      gigantica (rFgCatL1) were produced in vitro by fusion of BALB/c mice spleen cells
      immunized with rFgCatL1 and mouse myeloma cells. Reactivity and specificity of
      these MoAbs were evaluated by indirect ELISA and immunoblotting techniques. Seven
      MoAb clones were selected from the stable hybridoma clones, namely 1E10, 1F5,
      3D11, 4B10, 4D3, 4E3 and 5E7. Clones 1E10, 1F5 and 3D11 were IgM, whereas clones
      4B10, 4D3, 4E3 and 5E7 were IgG1. All MoAbs had kappa light chain isotypes. All
      MoAbs reacted with rCatL1 at molecular weight (MW) 30kDa and with the native
      CatL1 at MW 27kDa in whole body (WB) extracts of metacercariae (Met), newly
      excysted juveniles (NEJ), 1, 3, 5-week-old juveniles (Ju), adult WB and adult
      excretory-secretory (ES) fractions, but not with adult tegumental antigens (TA).
      All of these MoAbs showed no cross-reactions with antigens of other parasites
      commonly found in ruminants and human, including Paramphistomum cervi, Eurytrema
      pancreaticum, Gigantocotyle explanatum, Schistosoma spindale, Schistosoma
      mansoni, Moniezia benedeni, Avitellina centripunctata, Trichuris sp., Haemonchus
      placei and Setaria labiato-papillosa. Localization of CatL1 in each developmental
      stages of F. gigantica by immunoperoxidase technique, using these MoAbs as
      probes, indicated that CatL1 was present at high concentration in the caecal
      epithelium and caecal lumen of metacercariae, NEJ, 1, 3, 5-week-old juveniles and
      adult fluke. This finding indicated that CatL1 is a copiously expressed parasite
      protein that is released into the ES, thus CatL1 and its MoAb could be a good
      candidate for immunodiagnosis of fasciolosis in ruminant and human. 

PMID- 24736228
TI  - A tour of the thymus: a review of thymic lesions with radiologic and pathologic
      correlation.
AB  - The thymus is routinely encountered on cross-sectional imaging studies of the
      chest. It has a variable appearance, undergoes dynamic changes during periods of
      stress, and demonstrates numerous different pathologic lesions. Understanding the
      imaging characteristics of these different lesions facilitates accurate
      radiographic diagnosis and can prevent unnecessary follow-up imaging and
      intervention. This article will review normal thymic anatomy and development,
      thymic hyperplasia and associated medical conditions, and the imaging and
      pathologic features of various benign and malignant thymic lesions. 

PMID- 24736229
TI  - Knowledge of diagnostic and risk factors in oral cancer: results from a large
      scale survey among non-dental healthcare providers in Northern Germany.
AB  - INTRODUCTION: A survey was conducted to assess the level of knowledge on oral
      cancer among different medical fields, in particular about diagnostic items and
      risk factors. MATERIAL AND METHODS: A self-administered questionnaire was mailed
      to physicians from various fields, such as otorhinolaryngology, general practice,
      internal medicine, and dermatology. RESULTS: 388 of the 2,952 questionnaires were
      returned (13.1%), subdivided into otorhinolaryngology (n = 33), internal medicine
      (n = 135), dermatology (n = 28), and general practice (n = 192). The average
      knowledge of risk factors was similar in the specialisations, ranging from 68%
      for internal medicine to 76% for otorhinolaryngology and 77% for dermatology. The
      three main risk factors: tobacco (93%-100%), alcohol (79%-100%), and prior oral
      cancer lesions (91%-100%) were the most commonly known. Regarding the diagnostic
      items, the average percentage of correct answers ranged from 69% for internal and
      general medicine to 77% for dermatologists. Continuous courses of education and
      the year of graduation were the only two variables that significantly related to
      a better level of knowledge of risk factors and diagnostic items. CONCLUSIONS:
      The average knowledge among the different medical fields was satisfying. These
      results demonstrated a robust base for all healthcare providers to continue
      working together to improve the early detection of oral cancer.

PMID- 24736230
TI  - High and low contraceptive use amongst young male offenders: a qualitative
      interview study.
AB  - OBJECTIVES: There are high rates of fatherhood and sexually transmitted
      infections (STIs) among young incarcerated men. Here we focus on a sample of men
      incarcerated in a Scottish Young Offender Institution, analysing their accounts
      of their contraceptive use. Those who report low or no use of contraception are
      compared with those who report high use. METHODS: Semi-structured interviews with
      40 young male offenders, aged 16-21 years. Participants were purposively sampled
      using answers from a questionnaire administered to 67 inmates. Data from those
      men (n=31) reporting either high (n=14) or low/no use (n=17) of contraception are
      analysed here. RESULTS: Low users emphasise their desire for pleasure and appear
      fatalistic about both pregnancy and disease prevention. High users report a
      strong desire to protect themselves and their 'manliness' by using condoms to
      avoid the risk of STIs and, to a lesser extent, pregnancy. Both sets of men
      present themselves in a traditionally masculine way, with high users emphasising
      power, authority and self-control to justify their non-risk-taking contraceptive
      behaviour. CONCLUSIONS: The masculine narrative regarding self-protection,
      utilised by the high users, may be an effective method of intervention with
      potential and actual low users. Conventional masculinity valorises risk-taking
      but if particular forms of risk avoidance - condom use - can be legitimised as
      confirming one's masculinity it may be possible to persuade low users to adopt
      them. The opportunity to work with young men whilst incarcerated should be
      grasped.

PMID- 24736231
TI  - Mismatch negativity at Fz in response to within-category changes of the vowel
      /i/.
AB  - The amplitude of the mismatch negativity response for acoustic within-category
      deviations in speech stimuli was investigated by presenting participants with
      different exemplars of the vowel /i/ in an odd-ball paradigm. The deviants
      differed from the standard either in terms of fundamental frequency, the first
      formant, or the second formant. Changes in fundamental frequency are generally
      more salient than changes in the first formant, which in turn are more salient
      than changes in the second formant. The mismatch negativity response was expected
      to reflect this with greater amplitude for more salient deviations. The
      fundamental frequency deviants did indeed result in greater amplitude than both
      first formant deviants and second formant deviants, but no difference was found
      between the first formant deviants and the second formant deviants. It is
      concluded that greater difference between standard and within-category deviants
      across different acoustic dimensions results in greater mismatch negativity
      amplitude, suggesting that the processing of linguistically irrelevant changes in
      speech sounds may be processed similar to nonspeech sound changes. 

PMID- 24736232
TI  - Is brain damage really involved in the pathogenesis of obstructive sleep apnea?
AB  - Obstructive sleep apnea (OSA) syndrome is a surprisingly complex and highly
      individualized disease, with different factors contributing toward the disease
      process. Many factors can induce OSA disease, such as hypertrophy uvula,
      adenoidectomy, tonsil caused by mechanical obstruction of the airway, airway
      obstruction on obesity cause of decubitus, etc.; in addition, abnormal structure
      and function of the central nervous system (CNS) is also one of the important
      factors. This paper examines the relationship of the CNS with the onset of OSA.
      Evidence has shown that dysfunction of the CNS may be related to the occurrence
      of OSA. Although modification of the behaviors of the motor neurons may offer a
      potentially interesting means of controlling the airway, human afferent and motor
      pathways that regulate eupnea are still poorly understood. Combining some
      clinical phenomena of patients with cerebral hemorrhage or brain trauma at the
      temporal lobe, it seems that no close relation with OSA has been observed in
      clinical work and animal experiments; however, CNS damage at the temporal lobe is
      involved in the pathogenesis of OSA. This article examines the role of the CNS in
      the pathogenesis of OSA and its mechanisms. We have summarized previous findings
      of OSA-related brain damage, which were obtained by brain functional MRI,
      clinical, and animal experiment data to better understand the roles of the CNS in
      the pathogenesis of OSA. More specifically, this review summarizes how altered
      activity of the limbic system and its related structures could be associated with
      the occurrence of OSA. This conclusion may contribute toward our understanding of
      nosogenesis and the treatment of OSA. 

PMID- 24736233
TI  - Secretion of IL-16 through TNFR1 and calpain-caspase signaling contributes to
      MRSA pneumonia.
AB  - Staphylococcus aureus is a major cause of severe pneumonia. Multiple mechanisms
      of proinflammatory signaling are activated to recruit immune cells into the
      airway in response to S. aureus. We found that interleukin-16 (IL-16), a T cell
      cytokine that binds CD4, is potently activated by S. aureus, specifically by
      protein A (SpA), and to a much greater extent than by Gram-negative pathogens or
      lipopolysaccharide. IL-16 production involved multiple signals including ligation
      of tumor necrosis factor receptor (TNFR) family members or epidermal growth
      factor receptor, both receptors for SpA and generation of Ca(2+) fluxes to
      activate calpains and caspase-3. Although human airway epithelial cells, vascular
      endothelial cells, THP-1 and Jurkat T cells released IL-16 in response to S.
      aureus in vitro, in a murine model of pneumonia, CD4(+) cells were the major
      source of IL-16 suggesting the involvement of an autocrine signaling pathway. The
      production of IL-16 contributed to lung damage as neutralization of IL-16
      enhanced S. aureus clearance and resulted in diminished lung pathology in S.
      aureus pneumonia. Our results suggest that the ability of S. aureus to activate
      TNFR1 and Ca(2+)/calpain signaling contribute to T cell activation and excessive
      inflammation in the setting of acute pneumonia. 

PMID- 24736235
TI  - Sex-related differences of acute stroke unit care: results from the Austrian
      stroke unit registry.
AB  - BACKGROUND AND PURPOSE: Sex-related differences in quality of acute stroke care
      are an important concern with limited data available, specifically regarding
      stroke unit (SU) setting. We used the prospective nationwide Austrian SU registry
      to address this issue. METHODS: Our analysis covered an 8-year time period
      (January 2005 to December 2012) during which all patients with transient ischemic
      attack or ischemic stroke admitted to 1 of 35 Austrian SU had been captured in
      the registry. These data were analyzed for age-adjusted preclinical and clinical
      characteristics and quality of acute stroke care in men and women. In addition,
      we assessed the outcome at 3 months in multivariate analysis. RESULTS: A total of
      47 209 individuals (47% women) had received SU care. Women were significantly
      older (median age: 77.9 versus 70.3 years), had higher pre-existing disability
      and more severe strokes. Correcting for age, no significant sex-related
      differences in quality of care were identified with comparable onset-to-door
      times, times to and rates of neuroimaging, as well as door-to-needle times and
      rates of intravenous thrombolysis (14.5% for both sexes). Despite equal acute
      stroke care and a comparable rate of neurorehabilitation, women had a worse
      functional outcome at 3-month follow-up (modified Rankin scale 3-5: odds ratio,
      1.26; 95% confidence interval [1.17-1.36]), but a lower mortality (odds ratio,
      0.70; 95% confidence interval [0.78-0.88]) after correcting for confounders.
      CONCLUSIONS: We identified no disproportions in quality of care in the acute SU
      setting between men and women, but the outcome was significantly different.
      Further studies on the poststroke period including socioeconomic aspects are
      needed to clarify this finding.

PMID- 24736236
TI  - Atherogenic dyslipidemia and residual cardiovascular risk in statin-treated
      patients.
AB  - BACKGROUND AND PURPOSE: Treatment with statins reduces the rate of cardiovascular
      events in high-risk patients, but residual risk persists. At least part of that
      risk may be attributable to atherogenic dyslipidemia characterized by low high
      density lipoprotein cholesterol (<=40 mg/dL) and high triglycerides
      (triglycerides>=150 mg/dL). METHODS: We studied subjects with stroke or transient
      ischemic attack in the Prevention of Cerebrovascular and Cardiovascular Events of
      Ischemic Origin With Terutroban in Patients With a History of Ischemic Stroke or
      Transient Ischemic Attack (PERFORM; n=19,100) and Stroke Prevention by Aggressive
      Reduction in Cholesterol Levels (SPARCL; n=4731) trials who were treated with a
      statin and who had high-density lipoprotein cholesterol and triglycerides
      measurements 3 months after randomization (n=10,498 and 2900, respectively). The
      primary outcome measure for this exploratory analysis was the occurrence of major
      cardiovascular events (nonfatal myocardial infarction, nonfatal stroke, or
      cardiovascular death). We also performed a time-varying analysis to account for
      all available high-density lipoprotein cholesterol and triglyceride measurements.
      RESULTS: A total of 10% of subjects in PERFORM and 9% in SPARCL had atherogenic
      dyslipidemia after >=3 months on start statin therapy. After a follow-up of 2.3
      years (PERFORM) and 4.9 years (SPARCL), a major cardiovascular event occurred in
      1123 and 485 patients in the 2 trials, respectively. The risk of major
      cardiovascular events was higher in subjects with versus those without
      atherogenic dyslipidemia in both PERFORM (hazard ratio, 1.36; 95% confidence
      interval, 1.14-1.63) and SPARCL (hazard ratio, 1.40; 95% confidence interval,
      1.06-1.85). The association was attenuated after multivariable adjustment (hazard
      ratio, 1.23; 95% confidence interval, 1.03-1.48 in PERFORM and hazard ratio,
      1.24; 95% confidence interval, 0.93-1.65 in SPARCL). Time-varying analysis
      confirmed these findings. CONCLUSIONS: The presence of atherogenic dyslipidemia
      was associated with higher residual cardiovascular risk in PERFORM and SPARCL
      subjects with stroke or transient ischemic attack receiving statin therapy.
      Specific therapeutic interventions should now be trialed to address this residual
      risk.

PMID- 24736234
TI  - Systemic impact of intestinal helminth infections.
AB  - In this review, we examine the evidence that intestinal helminths can control
      harmful inflammatory responses and promote homeostasis by triggering systemic
      immune responses. Induction of separable components of immunity by helminths,
      which includes type 2 and immune regulatory responses, can both contribute toward
      the reduction in harmful type 1 immune responses that drive certain inflammatory
      diseases. Despite inducing type 2 responses, intestinal helminths may also
      downregulate harmful type 2 immune responses including allergic responses. We
      consider the possibility that intestinal helminth infection may indirectly affect
      inflammation by influencing the composition of the intestinal microbiome. Taken
      together, the studies reviewed herein suggest that intestinal helminth-induced
      responses have potent systemic effects on the immune system, raising the
      possibility that whole parasites or specific molecules produced by these
      metazoans may be an important resource for the development of future
      immunotherapies to control inflammatory diseases. 

PMID- 24736237
TI  - Assessing the performance of the Framingham Stroke Risk Score in the reasons for
      geographic and racial differences in stroke cohort.
AB  - BACKGROUND AND PURPOSE: The most well-known stroke risk score is the Framingham
      Stroke Risk Score (FSRS), which was developed during the higher stroke risk
      period of the 1990s and has not been validated for blacks. We assessed the
      performance of the FSRS among participants in the Reasons for Geographic and
      Racial Differences in Stroke (REGARDS) study to determine whether it is useful in
      both blacks and whites. METHODS: Expected annualized stroke rates from the FSRS
      were compared with observed stroke rates overall and within strata defined by
      FSRS risk factors (age, sex, systolic blood pressure, use of antihypertensive
      medications, diabetes mellitus, smoking, atrial fibrillation, left ventricular
      hypertrophy, and prevalent coronary heart disease). RESULTS: Among 27 748
      participants stroke-free at baseline, 715 stroke events occurred over 5.6 years
      of follow-up. FSRS-estimated incidence rates of stroke were 1.6* higher than
      observed for black men, 1.9* higher for white men, 1.7* higher for black women,
      and 1.7* higher for white women. This overestimation was consistent among most
      subgroups of FSRS factors, although the magnitude of overestimation varied by the
      risk factor assessed. CONCLUSIONS: Although higher FSRS was associated with
      higher stroke risk, the FSRS overestimated the observed stroke rates in this
      study, particularly in certain subgroups. This may be because of temporal
      declines in stroke rates, secular trends in prevention treatments, or differences
      in populations studied. More accurate estimates of event rates are critical for
      planning research, including clinical trials, and targeting health-care efforts.

PMID- 24736238
TI  - Improved hemodynamic parameters in middle cerebral artery infarction after
      decompressive craniectomy.
AB  - BACKGROUND AND PURPOSE: Decompressive craniectomy (DC) reduces mortality and
      improves functional outcome in patients with malignant middle cerebral artery
      infarction. However, little is known regarding the impact of DC on cerebral
      hemodynamics. Therefore, our goal was to study the hemodynamic changes that may
      occur in patients with malignant middle cerebral artery infarction after DC and
      to assess their relationship with outcomes. METHODS: Twenty-seven patients with
      malignant middle cerebral artery infarction who were treated with DC were
      studied. The perfusion CT hemodynamic parameters, mean transit time, cerebral
      blood flow, and cerebral blood volume were evaluated preoperatively and within
      the first 24 hours after DC. RESULTS: There was a global trend toward improved
      cerebral hemodynamics after DC. Preoperative and postoperative absolute mean
      transit times were associated with mortality at 6 months, and the ratio of post-
      and preoperative cerebral blood flow was significantly higher in patients with
      favorable outcomes than those with unfavorable outcomes. Patients who underwent
      surgery 48 hours after stroke, those with midline brain shift>10 mm, and those
      who were >55 years showed no significant improvement in any perfusion CT
      parameters. CONCLUSIONS: DC improves cerebral hemodynamics in patients with
      malignant middle cerebral artery infarction, and the level of improvement is
      related to outcome. However, some patients did not seem to experience any
      additional hemodynamic benefit, suggesting that perfusion CT may play a role as a
      prognostic tool in patients undergoing DC after ischemic stroke.

PMID- 24736239
TI  - Update on transient ischemic attack nursing care.

PMID- 24736240
TI  - Localized retinal nerve fiber layer defects and stroke.
AB  - BACKGROUND AND PURPOSE: Because the blood circulation system of retina and brain
      are closely related to each other, we examined whether stroke is associated with
      localized retinal nerve fiber layer defects (RNFLDs). METHODS: Patients with
      acute ischemic stroke as part of a hospital-based study group were compared with
      the participants of the population-based group Beijing Eye Study. The retina was
      imaged by spectral-domain optical coherence tomography for the detection of
      localized RNFLDs. RESULTS: The study included 154 patients with acute ischemic
      stroke and 2890 subjects from the Beijing Eye Study for whom optical coherence
      tomographic images of the retinal nerve fiber layer and data on a previous
      cerebral stroke were available. In logistic regression analysis, acute stroke was
      significantly associated with localized RNFLDs (P<0.001; odds ratio, 6.23; 95%
      confidence interval, 4.17-9.30) after adjusting for age, male sex, arterial
      hypertension, diabetes mellitus, and higher concentration of the C-reactive
      protein. In a similar manner, previous stroke was associated with localized
      RNFLDs (P=0.04; odds ratio, 1.48; 95% confidence interval, 1.02-2.16) in
      multivariate analysis. In a reverse manner, presence of localized RNFLDs was
      associated with cerebral stroke (P<0.001; odds ratio, 3.54; 95% confidence
      interval, 2.68-4.67) after adjusting for age, sex, and prevalence of diabetes
      mellitus. CONCLUSIONS: Localized RNFLDs showed a strong association with previous
      or acute cerebrovascular stroke and vice versa after adjustment for other
      systemic and ocular factors. Localized RNFLDs that can be assessed by noninvasive
      optical coherence tomographic imaging may be added to the panoply of retinal
      morphological features of stroke.

PMID- 24736241
TI  - Sex differences in trends of incidence and mortality of first-ever stroke in
      rural Tianjin, China, from 1992 to 2012.
AB  - BACKGROUND AND PURPOSE: Sex differences in secular trends of stroke incidence are
      rarely reported. We aimed to explore sex differences in incidence and mortality
      of stroke in rural China from 1992 to 2012. METHODS: In 1992, 14 920 residents
      were recruited to participate in the Tianjin Brain Study, a population-based
      study on stroke surveillance. Stroke events and all deaths were annually
      registered. RESULTS: We observed 908 incident strokes (366 in women) from 1992 to
      2012. Women were significantly younger than men (64+/-12 versus 68+/-11 years) in
      1992 to 1998 (P=0.024). The incidence of first-ever stroke per 100 000 person
      years for men was 166 in 1992 to 1998, 227 in 1999 to 2005, and 376 in 2006 to
      2012; for women, the rates were 86 (1992-1998), 148 (1999-2005), and 264 (2006
      2012). From 1992 to 2012, the incidence grew annually by 5.8% in men and 8.0% in
      women. The male/female incidence ratio declined significantly: 1.9 in 1992 to
      1998, 1.5 in 1999 to 2005, and 1.4 in 2006 to 2012. There were no significant sex
      differences in mortality. The prevalence of obesity and diabetes mellitus, the
      levels of total cholesterol and triglycerides, and the age of menopause and
      reproductive years in women concurrently increased in 2011. CONCLUSIONS: There
      was a significant increase in the incidence of first-ever stroke in women
      annually and a declining trend in the male/female rate ratio in rural China
      during the past 21 years. These results suggest that stroke will become one of
      the major diseases affecting women in future decades in China.

PMID- 24736243
TI  - Evaluation of the clinical and cost effectiveness of intermediate care clinics
      for diabetes (ICCD): a multicentre cluster randomised controlled trial.
AB  - BACKGROUND: Configuring high quality care for the rapidly increasing number of
      people with type 2 diabetes (T2D) is a major challenge worldwide for both
      providers and commissioners. In the UK, about two thirds of people with T2D are
      managed entirely in primary care, with wide variation in management strategies
      and achievement of targets. Pay for performance, introduced in 2004, initially
      resulted in improvements but disparities exist in ethnic minorities and the
      improvements are levelling off. Community based, intermediate care clinics for
      diabetes (ICCDs) were considered one solution and are functioning across the UK.
      However, there is no randomised trial evidence for the effectiveness of such
      clinics. TRIAL DESIGN, METHODS AND FINDINGS: This is a cluster-randomised trial,
      involving 3 primary care trusts, with 49 general practices randomised to usual
      care (n=25) or intervention (ICCDs; n=24). All eligible adult patients with T2D
      were invited; 1997 were recruited and 1280 followed-up after 18-months
      intervention. PRIMARY OUTCOME: achievement of all three of the NICE targets
      [(HbA1c <= 7.0%/53 mmol/mol; Blood Pressure <140/80 mmHg; cholesterol <154 mg/dl
      (4 mmol/l)]. PRIMARY OUTCOME was achieved in 14.3% in the intervention arm vs.
      9.3% in the control arm (p=0.059 after adjustment for covariates). The odds ratio
      (95% CI) for achieving primary outcome in the intervention group was 1.56 (0.98,
      2.49). Primary care and community clinic costs were significantly higher in the
      intervention group, but there were no significant differences in hospital costs
      or overall healthcare costs. An incremental cost-effectiveness ratio (ICER) of
      +L7,778 per QALY gained, indicated ICCD was marginally more expensive at
      producing health gain. CONCLUSIONS: Intermediate care clinics can contribute to
      improving target achievement in patients with diabetes. Further work is needed to
      investigate the optimal scale and organisational structure of ICCD services and
      whether, over time, their role may change as skill levels in primary care
      increase. TRIAL REGISTRATION: ClinicalTrials.gov NCT00945204; National Research
      Register (NRR) M0014178167.

PMID- 24736244
TI  - Seizures and ST-segment elevation: Chagas disease.

PMID- 24736242
TI  - Identification of differentially expressed genes in leaf of Reaumuria soongorica
      under PEG-induced drought stress by digital gene expression profiling.
AB  - Reaumuria soongorica (Pall.) Maxim., a resurrection semi-shrub, is a typical
      constructive and dominant species in desert ecosystems in northwestern China.
      However, the gene expression characteristics of R. soongorica under drought
      stress have not been elucidated. Digital gene expression analysis was performed
      using Illumina technique to investigate differentially expressed genes (DEGs)
      between control and PEG-treated samples of R. soongorica. A total of 212,338 and
      211,052 distinct tags were detected in the control and PEG-treated libraries,
      respectively. A total of 1,325 genes were identified as DEGs, 379 (28.6%) of
      which were up-regulated and 946 (71.4%) were down-regulated in response to
      drought stress. Functional annotation analysis identified numerous drought
      inducible genes with various functions in response to drought stress. A number of
      regulatory proteins, functional proteins, and proteins induced by other stress
      factors in R. soongorica were identified. Alteration in the regulatory proteins
      (transcription factors and protein kinase) may be involved in signal
      transduction. Functional proteins, including flavonoid biosynthetic proteins,
      late embryogenesis abundant (LEA) proteins, small heat shock proteins (sHSP), and
      aquaporin and proline transporter may play protective roles in response to
      drought stress. Flavonoids, LEA proteins and sHSP function as reactive oxygen
      species scavenger or molecular chaperone. Aquaporin and proline transporters
      regulate the distribution of water and proline throughout the whole plant. The
      tolerance ability of R. soongorica may be gained through effective signal
      transduction and enhanced protection of functional proteins to reestablish
      cellular homeostasis. DEGs obtained in this study may provide useful insights to
      help further understand the drought-tolerant mechanism of R. soongorica. 

PMID- 24736245
TI  - Into thin air: shrinking lung syndrome.

PMID- 24736246
TI  - Drug-induced dilemma: angiokeratomas and decreased renal function.

PMID- 24736247
TI  - Ibrutinib (Imbruvica) for chronic lymphocytic leukemia.

PMID- 24736248
TI  - Anoro Ellipta: an inhaled umeclidinium/vilanterol combination for COPD.

PMID- 24736249
TI  - Inhaled loxapine (Adasuve) for acute agitation.

PMID- 24736250
TI  - Long-read sequencing of chicken transcripts and identification of new transcript
      isoforms.
AB  - The chicken has long served as an important model organism in many fields, and
      continues to aid our understanding of animal development. Functional genomics
      studies aimed at probing the mechanisms that regulate development require high
      quality genomes and transcript annotations. The quality of these resources has
      improved dramatically over the last several years, but many isoforms and genes
      have yet to be identified. We hope to contribute to the process of improving
      these resources with the data presented here: a set of long cDNA sequencing
      reads, and a curated set of new genes and transcript isoforms not currently
      represented in the most up-to-date genome annotation currently available to the
      community of researchers who rely on the chicken genome. 

PMID- 24736251
TI  - [Medication adherence to secondary prevention for coronary artery disease].
AB  - We compared the use of evidence-based secondary prevention drugs for coronary
      artery disease at hospital discharge and 3 years of follow-up in a group of
      patients associated to an integrated network of health services. We conducted a
      retrospective group study that included 125 patients under 80 years of age who
      were hospitalized for acute coronary syndrome. McNemar's test was used to compare
      values at baseline and 3 years. The mean age of of participants was 63.7 years
      (SD +/- 10.08) and 65.6% (95% CI 56.6-73.9) of male sex. The average follow-up
      time was 2.94 years (SD +/- 0.25). The use of secondary prevention drugs for
      coronary heart disease decreased at 3 years of follow-up: anti-platelet 97.6 to
      88.0% (p = 0.012), beta-blockers 94.4 to 84.8% (p = 0.021) and statins 83.7 to
      91.2% (p = 0.035). Patients medicated with a combination of anti-platelet, beta
      blockers and statins showed a decrease from 86.4 to 66.3% (p < 0.0001). It is
      necessary to study the causes for the decreased adherence to long-term cardio
      protective drugs. 

PMID- 24736252
TI  - [Adherence to interdisciplinary Pulmonary Rehabilitation Program].
AB  - Participation in a Pulmonary Rehabilitation Program (PRP) improves dyspnea,
      functional capacity and quality of life in patients with chronic respiratory
      disease. A retrospective study was carried out to identify variables related to
      compliance in an out patient PRP at an Argentine center and to evaluate the
      results in compliant patients. The PRP included an "acquisition" stage consisting
      of 16 weeks of supervised training twice weekly and lectures on treatment
      benefits, inhalation devices used, smoking cessation, symptoms recognition and
      flair up management, among others. Patients were reassessed after this stage.
      Patients completing the acquisition stage were considered PRP compliant. Of 388
      patients evaluated for admission 102 (26.3%) complied with PRP. Multiple logistic
      regression analysis (Forward Stepwise; p < 0.10 to be eligible for entry into the
      model) was used to identify factors related to "program compliance". The final
      model was as follows: having health insurance coverage (OR = 3.99; CI90% = 2.24
      7.12), commute time under 60 minutes (OR = 2.07; CI90% = 1.37-3.11) and financial
      capacity (OR = 2.11; CI90% = 1.03-4.31). All patients complied with the PRP
      showed significant improvement in the six-minute walking test and quality of
      life. The results warn about low compliance and their relationship with
      socioeconomic variables. 

PMID- 24736253
TI  - [A fellowship with Alejandro Lipschutz with translational projections].

PMID- 24736254
TI  - [Hereditary multiple exostosis].

PMID- 24736255
TI  - [Polysplenia / levoisomerism].

PMID- 24736256
TI  - [Hemodialysis to remove anticoagulant dabigatran during emergencies].
AB  - Dabigatran is an oral anticoagulant from the class of the direct thrombin
      inhibitors, indicated for prevention of thromboembolic events in patients with
      non valvular atrial fibrillation. Unlike warfarin, dabigatran has no known
      antidote. Hemodialysis has been suggested as a method for removing dabigatran and
      thereby reducing its anticoagulant effect. We report the case of a patient with a
      known history of atrial fibrillation, treated with dabigatran, who was admitted
      for emergency abdominal surgery. At six hours after the last dose received,
      coagulation studies were altered. In absence of an antidote to reverse its
      effects, it was decided to perform hemodialysis. After three hours of dialysis
      coagulation parameters were improved and the patient underwent surgery without
      showing abnormal bleeding during surgery or in the postoperative period. 

PMID- 24736257
TI  - [Pharmacological and mechanical thrombolysis in submassive pulmonary embolism].
AB  - Thromboembolic pulmonary disease is challenging for physicians when diagnosed in
      acute, sub-acute and chronic clinical patients, not only due to its morbi
      mortality, but also because of its complex therapeutic management. Severity of
      the acute condition and potential commitment of right ventricular systolic
      function require therapeutic strategies, sometimes combined, in order to change
      the disease's course, optimizing patient survival. Pharmacological and mechanical
      thrombolysis are useful therapeutic tools for patients suffering from severe
      acute pulmonary embolism. This study refers to a young woman who developed a sub
      massive pulmonary embolism, of sub-acute onset. She underwent the combined
      sequential therapeutic strategy of pharmacological and mechanical thrombolysis
      with successful outcome. 

PMID- 24736258
TI  - [Enophthalmos secondary to an orbital varix].
AB  - The enophthalmos is a rare cause of consultation in medical practice. The
      majority of cases are due to orbital space enlargement of traumatic origin. We
      report the case of a 63 year old patient with progressive enophthalmos of the
      left eye, with twelve years of evolution. Ophthalmologic examination revealed the
      presence of a marked enophthalmos on the left side, which improved significantly
      with Valsalva maneuvers. A CT scan and an MRI of the orbit allowed diagnosing
      uncomplicated orbital varices. Orbital varices are rare and usually manifest by
      episodes of intermittent exophthalmos. However, on rare occasions, repeated
      distension and collapse can lead to progressive enophthalmos by orbital fat
      atrophy. 

PMID- 24736259
TI  - [Immune reconstitution syndrome in an HIV-infected patient and Pneumocystis
      jirovecii pneumonia].
AB  - Immune reconstitution syndrome is a set of acute inflammatory phenomena that
      occur as a result of restored immunity generating a paradoxical worsening of a
      prior infection or an inflammatory process. This syndrome occurs in human
      immunodeficiency virus infected patients after starting antiretroviral treatment.
      The most frequent associated infections are those produced by mycobacteria,
      herpes, cryptococcosis, hepatitis B, cytomegalovirus, Pneumocystis jirovecii and
      worsening of progressive multifocal leukoencephalopathy secondary to JC virus. We
      present the case of a patient with human immunodeficiency virus who developed the
      immune reconstitution syndrome secondary to Pneumocystis jirovecii. 

PMID- 24736260
TI  - [CFTR and ENaC functions in cystic fibrosis].
AB  - Cystic fibrosis is caused by dysfunction or lack of the cystic fibrosis
      transmembrane conductance regulator (CFTR), a chloride channel that has a key
      role in maintaining ion and water homoeostasis in different tissues. CFTR is a
      cyclic AMP-activated Cl- channel found in the apical and basal plasma membrane of
      airway, intestinal, and exocrine epithelial cells. One of CFTR's primary roles in
      the lungs is to maintain homoeostasis of the airway surface liquid layer through
      its function as a chloride channel and its regulation of the epithelial sodium
      channel ENaC. More than 1900 CFTR mutations have been identified in the cftr
      gene. The disease is characterized by viscous secretions of the exocrine glands
      in multiple organs and elevated levels of sweat sodium chloride. In cystic
      fibrosis, salt and fluid absorption is prevented by the loss of CFTR and ENaC is
      not appropriately regulated, resulting in increased fluid and sodium resorption
      from the airways and formation of a contracted viscous surface liquid layer. In
      the sweat glands both Na+ and Cl- ions are retained in the lumen, causing
      significant loss of electrolytes during sweating. Thus, elevated sweat NaCl
      concentration is the basis of the classic pilocarpine-induced sweat test as a
      diagnostic feature of the disease. Here we discuss the ion movement of Cl- and
      Na+ ions in two tissues, sweat glands and in the air surface as well as the role
      of ENaC in the pathogenesis of cystic fibrosis. 

PMID- 24736261
TI  - [Expression of SOX11 transcription factor. Its implication in mantle cell
      lymphoma].
AB  - SOX11, belonging to the family of genes SOXC, is a transcript factor involved in
      the embryonic neurogenesis and tissue remodeling, also participating in the
      control of cell proliferation. Its role in lymphomagenesis still remains unknown.
      Recent studies have shown aberrant SOX11 nuclear protein expression as well as
      mRNA levels in patients with mantle cell lymphoma (MCL). Although the majority of
      these lymphomas have an aggressive clinical course, there is a subgroup of
      patients with an indolent clinical evolution, suggesting a greater heterogeneity
      of this disease. Currently, there are contradictions regarding the association of
      SOX11 gene expression and outcome in MCL, while some authors have related the
      lack of SOX11 expression with good prognosis, others find it associated with an
      adverse clinical course. This difference in the gene expression could be
      associated to epigenetic mechanisms such as modifications at the histone level
      and DNA methylation that would allow the aberrant expression of this gene in some
      lymphoid neoplasias, including LCM. More knowledge of gene SOX11 in LCM will lead
      to a greater understanding of those mechanisms involved in the pathogenesis and
      progression of this lymphoma, also the involvement of SOX11 in these processes. 

PMID- 24736262
TI  - [New physiopathological knowledge applied to migraine therapy and prophylaxis].
AB  - Migraine is a very common condition that has a significant socioeconomic impact.
      Based on the most recent reports from the World Health Organization, its
      diagnosis and treatment are far from being optimal. Specialists have made great
      efforts to classify headaches, including migraines, in order to have a useful
      diagnostic tool and to guide treatment. On the other hand, advances made in the
      knowledge of the pathophysiology of migraines, new treatment options were
      developed. These new options include onabotulinum toxin A and topiramate. The
      prompt detection of migraine disorders and an appropriate treatment, both
      symptomatic and preventive, are key to relieve the personal, familiar, and social
      burden with special focus on chronic migraine. 

PMID- 24736263
TI  - Rheumatoid arthritis associated interstitial lung disease: a review.
AB  - Rheumatoid arthritis is a common inflammatory disease affecting about 1% of the
      population. Interstitial lung disease is a serious and frequent complication of
      rheumatoid arthritis. Rheumatoid arthritis associated interstitial lung disease
      (RA-ILD) is characterized by several histopathologic subtypes. This article
      reviews the proposed pathogenesis and risk factors for RA-ILD. We also outline
      the important steps involved in the work-up of RA-ILD and review the evidence for
      treatment and prognosis. 

PMID- 24736264
TI  - [Septic shock evolving in acute lung edema and multiorgan failure].

PMID- 24736265
TI  - [Translational medicine, fashion or necessity?].

PMID- 24736266
TI  - [Dying of old age. What autopsies say?].

PMID- 24736267
TI  - [Farewell to Samuel Finkielman].

PMID- 24736268
TI  - [Samuel Finkielman (1932-2013). A humanist].

PMID- 24736269
TI  - [Acute lymphatic leukemia presenting in fatal fulminant hepatitis].

PMID- 24736270
TI  - [On scientific research in health institutions of the city of Buenos Aires].

PMID- 24736271
TI  - A physicians' wish list for the clinical application of intestinal metagenomics.
AB  - Christoph Steininger and colleagues explore how multiple infectious, autoimmune,
      metabolic, and neoplastic diseases have been associated with changes in the
      intestinal microbiome, although a cause-effect relationship is often difficult to
      establish. Integration of metagenomics into clinical medicine is a challenge, and
      the authors highlight clinical approaches that are of high priority for the
      useful medical application of metagenomics. Please see later in the article for
      the Editors' Summary. 

PMID- 24736272
TI  - Medical students perceive better group learning processes when large classes are
      made to seem small.
AB  - OBJECTIVE: Medical schools struggle with large classes, which might interfere
      with the effectiveness of learning within small groups due to students being
      unfamiliar to fellow students. The aim of this study was to assess the effects of
      making a large class seem small on the students' collaborative learning
      processes. DESIGN: A randomised controlled intervention study was undertaken to
      make a large class seem small, without the need to reduce the number of students
      enrolling in the medical programme. The class was divided into subsets: two small
      subsets (n=50) as the intervention groups; a control group (n=102) was mixed with
      the remaining students (the non-randomised group n~100) to create one large
      subset. SETTING: The undergraduate curriculum of the Maastricht Medical School,
      applying the Problem-Based Learning principles. In this learning context,
      students learn mainly in tutorial groups, composed randomly from a large class
      every 6-10 weeks. INTERVENTION: The formal group learning activities were
      organised within the subsets. Students from the intervention groups met
      frequently within the formal groups, in contrast to the students from the large
      subset who hardly enrolled with the same students in formal activities. MAIN
      OUTCOME MEASURES: Three outcome measures assessed students' group learning
      processes over time: learning within formally organised small groups, learning
      with other students in the informal context and perceptions of the intervention.
      RESULTS: Formal group learning processes were perceived more positive in the
      intervention groups from the second study year on, with a mean increase of
      beta=0.48. Informal group learning activities occurred almost exclusively within
      the subsets as defined by the intervention from the first week involved in the
      medical curriculum (E-I indexes>-0.69). Interviews tapped mainly positive effects
      and negligible negative side effects of the intervention. CONCLUSION: Better
      group learning processes can be achieved in large medical schools by making large
      classes seem small.

PMID- 24736273
TI  - Protein dynamics of the HIF-2alpha PAS-B domain upon heterodimerization and
      ligand binding.
AB  - Hypoxia-Inducible Factor (HIF) transcription factors are heterodimeric proteins
      involved in the regulation of oxygen homeostatis. Their upregulation has been
      related to several tumors with a remarkably poor clinical outcome. The recent
      discovery of a druggable cavity in the HIF-2alpha PAS-B domain has opened an
      unprecedented opportunity for targeting the HIF-2alpha transcription factor in
      view of pharmaceutical strategies. Coincidentally, a novel compound able to
      selectively disrupt the HIF heterodimerization with a submicromolar activity has
      been reported. In this work, we investigated the molecular mechanisms responsible
      for the inhibition by comparing the dynamical features of the HIF-2alpha PAS-B
      monomer and the HIF-2alpha PAS-B/HIF-1beta PAS-B complex, in the ligand-bound and
      -unbound states. Plain and biased Molecular Dynamics were used to characterize
      the differential conformational changes both structurally and energetically. 

PMID- 24736274
TI  - Vitreous hyper-reflective dots in optical coherence tomography and cystoid
      macular edema after uneventful phacoemulsification surgery.
AB  - PURPOSE: To report the observation of hyper-reflective dots in the vitreous
      cavity using spectral domain optical coherence tomography (SD-OCT) after
      uneventful phacoemulsification cataract surgery and to investigate their
      association with cystoid macular edema (CME). MATERIALS AND METHODS: Medical
      records of consecutive Asian patients who had no preoperative retinopathy and
      underwent uneventful phacoemulsification cataract surgery from March 2012 through
      February 2013 were reviewed. SD-OCTs were performed before, 1 week, and 1 month
      after surgery. The number of vitreous hyper-reflective dots (VHDs) was counted in
      5 OCT images of high-definition 5-line raster scans. The development of CME was
      assessed using postoperative 1-month OCT. RESULTS: In 74 eyes of 74 patients, all
      of three SD-OCTs with a signal to noise ratio of 0.6 or more were available and
      were analyzed in this study. In preoperative OCT, the VHD was observed in 2
      (2.7%) of 74 eyes; one eye had 1 VHD and the other eye had 2 VHDs. In 72 eyes
      with no preoperative VHD, VHDs were observed in 40 (55.6%) eyes at 1 week after
      the surgery. In the multivariate analysis, the number of VHDs measured at 1 week
      after the surgery was significantly associated with CME development at 1 month
      after the surgery (odds ratio = 1.93, 95% confidence interval = 1.15 to 3.24, P =
      0.012). CONCLUSIONS: VHDs were frequently observed in OCT after uneventful
      phacoemulsification cataract surgery. VHDs observed at 1 week after the surgery
      may be a risk factor for the development of pseudophakic CME. Further studies are
      needed to identify the source of the VHDs.

PMID- 24736275
TI  - Comprehensive analysis of human cells motion under an irrotational AC electric
      field in an electro-microfluidic chip.
AB  - AC electrokinetics is a versatile tool for contact-less manipulation or
      characterization of cells and has been widely used for separation based on
      genotype translation to electrical phenotypes. Cells responses to an AC electric
      field result in a complex combination of electrokinetic phenomena, mainly
      dielectrophoresis and electrohydrodynamic forces. Human cells behaviors to AC
      electrokinetics remain unclear over a large frequency spectrum as illustrated by
      the self-rotation effect observed recently. We here report and analyze human
      cells behaviors in different conditions of medium conductivity, electric field
      frequency and magnitude. We also observe the self-rotation of human cells, in the
      absence of a rotational electric field. Based on an analytical competitive model
      of electrokinetic forces, we propose an explanation of the cell self-rotation.
      These experimental results, coupled with our model, lead to the exploitation of
      the cell behaviors to measure the intrinsic dielectric properties of JURKAT, HEK
      and PC3 human cell lines. 

PMID- 24736276
TI  - Mineral content and biochemical variables of Aloe vera L. under salt stress.
AB  - Despite the proven economic importance of Aloe vera, studies of saline stress and
      its effects on the biochemistry and mineral content in tissues of this plant are
      scarce. The objective of this study was to grow Aloe under NaCl stress of 0, 30,
      60, 90 and 120 mM and compare: (1) proline, total protein, and enzyme
      phosphoenolpyruvate carboxylase (PEP-case) in chlorenchyma and parenchyma
      tissues, and (2) ion content (Na, K, Ca, Mg, Cl, Fe, P. N, Zn, B, Mn, and Cu) in
      roots, stems, leaves and sprouts. Proline and PEP-case increased as salinity
      increased in both parenchyma and chlorenchyma, while total protein increased in
      parenchyma and decreased in chlorenchyma, although at similar salt concentrations
      total protein was always higher in chlorenchyma. As salinity increased Na and Cl
      ions increased in roots, stems, leaves, while K decreased only significantly in
      sprouts. Salinity increases typically caused mineral content in tissue to
      decrease, or not change significantly. In roots, as salinity increased Mg
      decreased, while all other minerals failed to show a specific trend. In stems,
      the mineral concentrations that changed were Fe and P which increased with
      salinity while Cu decreased. In leaves, Mg, Mn, N, and B decreased with salinity,
      while Cu increased. In sprouts, the minerals that decreased with increasing
      salinity were Mg, Mn, and Cu. Zinc did not exhibit a trend in any of the tissues.
      The increase in protein, proline and PEP-case activity, as well as the absorption
      and accumulation of cations under moderate NaCl stress caused osmotic adjustment
      which kept the plant healthy. These results suggest that Aloe may be a viable
      crop for soil irrigated with hard water or affected by salinity at least at
      concentrations used in the present study. 

PMID- 24736277
TI  - Human podoplanin-positive monocytes and platelets enhance lymphangiogenesis
      through the activation of the podoplanin/CLEC-2 axis.
AB  - Emerging studies suggested that murine podoplanin-positive monocytes (PPMs) are
      involved in lymphangiogenesis. The goal of this study was to demonstrate the
      therapeutic lymphangiogenesis of human PPMs by the interaction with platelets.
      Aggregation culture of human peripheral blood mononuclear cells (PBMCs) resulted
      in cellular aggregates termed hematospheres. During 5-day culture, PPMs expanded
      exponentially and expressed several lymphatic endothelial cell-specific markers
      including vascular endothelial growth factor receptor (VEGFR)-3 and well
      established lymphangiogenic transcription factors. Next, we investigated the
      potential interaction of PPMs with platelets that had C-type lectin-like receptor
      2 (CLEC-2), a receptor of podoplanin. In vitro coculture of PPMs and platelets
      stimulated PPMs to strongly express lymphatic endothelial markers and upregulate
      lymphangiogenic cytokines. Recombinant human CLEC-2 also stimulated PPMs through
      Akt and Erk signaling. Likewise, platelets in coculture with PPMs augmented
      secretion of a lymphangiogenic cytokine, interleukin (IL)-1-beta, via
      podoplanin/CLEC-2 axis. The supernatant obtained from coculture was able to
      enhance the migration, viability, and proliferation of lymphatic endothelial
      cell. Local injection of hematospheres with platelets significantly increased
      lymphatic neovascularization and facilitated wound healing in the full-thickness
      skin wounds of nude mice. Cotreatment with PPMs and platelets augments
      lymphangiogenesis through podoplanin/CLEC-2 axis, which thus would be a promising
      novel strategy of cell therapy to treat human lymphatic vessel disease. 

PMID- 24736278
TI  - Inflammation converts human mesoangioblasts into targets of alloreactive immune
      responses: implications for allogeneic cell therapy of DMD.
AB  - Stem cell therapy is a promising approach to regenerate healthy tissues starting
      from a limited amount of self-renewing cells. Immunological rejection of cell
      therapy products might represent a major limitation. In this study, we
      investigated the immunological functional profile of mesoangioblasts, vessel
      associated myogenic stem cells, currently tested in a phase 1-2a trial, active in
      our Institute, for the treatment of Duchenne muscular dystrophy. We report that
      in resting conditions, human mesoangioblasts are poorly immunogenic, inefficient
      in promoting the expansion of alloreactive T cells and intrinsically resistant to
      T-cell killing. However, upon exposure to interferon-gamma or differentiation
      into myotubes, mesoangioblasts acquire the ability to promote the expansion of
      alloreactive T cells and acquire sensitivity to T-cell killing. Resistance of
      mesoangioblasts to T-cell killing is largely due to the expression of the
      intracellular serine protease inhibitor-9 and represents a relevant mechanism of
      stem cell immune evasion. 

PMID- 24736279
TI  - Blood pressure measurement reliability among different racial-ethnic groups in a
      stroke prevention study.
AB  - OBJECTIVE: High blood pressure (BP) is commonly not diagnosed, and patients do
      not achieve target values when treated. Among 20,000 patients encompassing most
      races-ethnicities, we evaluated BP measurements and treatment response in a
      stroke prevention trial. Our goal was to identify BP measurement differences
      between clinical trial and patient determinations and among the racial-ethnic
      groups. MATERIALS AND METHODS: A total of 20,332 patients with ischemic stroke
      were randomized to receive antiplatelet treatment and 80 mg of telmisartan versus
      placebo. BP measurements were obtained at the first clinic visit and then 1 and 3
      months later and every 6 months thereafter. One week after the first clinic
      visit, patients were requested to report a BP measurement obtained elsewhere.
      Measurements at the trial clinics were obtained with the same electronic device.
      Statistical analysis was used to detect significant differences. RESULTS: The
      mean patient age was 66 years; 36% were women, and race-ethnicity comprised 58%
      Whites, 33% Asian, 4.9% Hispanic, and 4% Black. Overall, 74% of patients were
      hypertensive. BP varied between the race-ethnicity groups, being highest in
      Hispanics (145/85) and lowest in Blacks (144/82). BP at visits clinic 1,
      nonclinic 1A, and clinic 2 were, respectively, 144/84, 137/80, and 139/81 mmHg,
      with the difference between visits 1-2 and visit 1A being significant. BPs were
      normal in 42% of the cases at visit 1A, and of these, only 44% were normal at
      visit 1 and 57.6% were normal on visit 2. Similar findings were noted for all
      race-ethnicity groups. CONCLUSION: BP values varied among race-ethnicities and
      showed differences between clinic and patient measurements. This finding
      questions the reliability of self-reported BP and has implications for BP
      management in daily clinical practice.

PMID- 24736280
TI  - First seizures in adults.

PMID- 24736281
TI  - Translational control of Arabidopsis meristem stability and organogenesis by the
      eukaryotic translation factor eIF3h.
AB  - Essentially all aboveground plant tissues develop from the stem cells in the
      primary shoot apical meristem. Proliferation of the stem cell population in the
      Arabidopsis shoot apical meristem is tightly controlled by a feedback loop formed
      primarily by the homeodomain transcription factor WUSCHEL (WUS) and the CLAVATA
      ligand-receptor system. In this study, it is shown that mutation of a translation
      initiation factor, eIF3h, causes a tendency to develop a strikingly enlarged
      shoot apical meristem with elevated and ectopic expression of WUS and CLAVATA3
      (CLV3). Many of the mRNAs that function in apical meristem maintenance possess
      upstream open reading frames (uORFs), translational attenuators that render
      translation partially dependent on eIF3h. Specifically, the mRNA for the receptor
      kinase, CLV1, is undertranslated in the eif3h mutant as shown by transient and
      transgenic expression assays. Concordant phenotypic observations include defects
      in organ polarity and in translation of another uORF-containing mRNA, ASYMMETRIC
      LEAVES 1 (AS1), in eif3h. In summary, the expression of developmental regulatory
      mRNAs is attenuated by uORFs, and this attenuation is balanced in part by the
      translation initiation factor, eIF3h. Thus, translational control plays a key
      role in Arabidopsis stem cell regulation and organogenesis.

PMID- 24736283
TI  - Decision-to-delivery interval (DDI) for emergency cesarean section (ECS) for
      nonreassuring fetal heart rate (NRFHR).

PMID- 24736282
TI  - The relationship between endothelial progenitor cell populations and epicardial
      and microvascular coronary disease-a cellular, angiographic and physiologic
      study.
AB  - BACKGROUND: Endothelial progenitor cells (EPCs) are implicated in protection
      against vascular disease. However, studies using angiography alone have reported
      conflicting results when relating EPCs to epicardial coronary artery disease
      (CAD) severity. Moreover, the relationship between different EPC types and the
      coronary microcirculation is unknown. We therefore investigated the relationship
      between EPC populations and coronary epicardial and microvascular disease.
      METHODS: Thirty-three patients with a spectrum of isolated left anterior
      descending artery disease were studied. The coronary epicardial and
      microcirculation were physiologically interrogated by measurement of fractional
      flow reserve (FFR), index of microvascular resistance (IMR) and coronary flow
      reserve (CFR). Two distinct EPC populations (early EPC and late outgrowth
      endothelial cells [OECs]) were isolated from these patients and studied ex vivo.
      RESULTS: There was a significant inverse relationship between circulating OEC
      levels and epicardial CAD severity, as assessed by FFR and angiography (r=0.371,
      p=0.04; r=-0.358, p=0.04; respectively). More severe epicardial CAD was
      associated with impaired OEC migration and tubulogenesis (r=0.59, p=0.005;
      r=0.589, p=0.004; respectively). Patients with significant epicardial CAD
      (FFR<0.75) had lower OEC levels and function compared to those without
      hemodynamically significant stenoses (p<0.05). In contrast, no such relationship
      was seen for early EPC number and function, nor was there a relationship between
      IMR and EPCs. There was a significant relationship between CFR and OEC function.
      CONCLUSIONS: EPC populations differ in regards to their associations with CAD
      severity. The number and function of OECs, but not early EPCs, correlated
      significantly with epicardial CAD severity. There was no relationship between
      EPCs and severity of coronary microvascular disease.

PMID- 24736284
TI  - Reply: To PMID 24565432.

PMID- 24736285
TI  - Preliminary development and validation of a new end-of-life patient-reported
      outcome measure assessing the ability of patients to finalise their affairs at
      the end of life.
AB  - INTRODUCTION: The ability of patients to finalise their affairs at the end of
      life is an often neglected aspect of quality of life (QOL) measurement in
      palliative care effectiveness research despite compelling evidence of the high
      value patients place on this domain. OBJECTIVE: This paper describes the
      preliminary development and evaluation of a new, single-item, end-of-life patient
      reported outcome measure (EOLPRO) designed to capture changes in the ability of
      patients to finalise their affairs at the end of life. METHODS: Cognitive
      interviews with purposively sampled Australian palliative care patients (N = 9)
      were analysed thematically to explore content validity. Simultaneously, secondary
      analysis of data from a randomised controlled trial comparing ketamine and
      placebo for the management of cancer pain (N = 185) evaluated: construct
      validity; test-retest reliability; and responsiveness. RESULTS: Preliminary
      findings suggest patients interpret the new measure consistently. The EOLPRO
      captures the ability to complete physical tasks and finalise practical matters
      although it is unclear whether emotional tasks or resolution of relationship
      issues are considered. Personal and financial affairs should be separated to
      allow for differences in ability for these two types of affairs. The significant
      correlation between performance status and EOLPRO scores (r = 0.41, p<0.01, n =
      137) and expected relationships between EOLPRO and proximity to death and
      constipation demonstrated construct validity. Pre- and post-treatment EOLPRO
      scores moderately agreed (n = 14, kappa = 0.52 [95% CI 0.19, 0.84]) supporting
      reliability. The measure's apparent lack of sensitivity to discriminate between
      treatment responders and non-responders may be confounded. CONCLUSION: Based on
      the preliminary findings, the EOLPRO should be separated into 'personal' and
      'financial' affairs with further testing suggested, particularly to verify
      coverage and responsiveness. Initial evaluation suggests that the single-item
      EOLPRO is a useful addition to QOL outcome measurement in palliative care
      effectiveness research because common palliative care specific QOL questionnaires
      do not include or explicitly capture this domain.

PMID- 24736287
TI  - Observational study of the effect of obesity on lung volumes.
AB  - BACKGROUND: Severe obesity causes respiratory morbidity and mortality. The impact
      of obesity on the mechanics of breathing is not fully understood. PATIENTS AND
      METHODS: We undertook a comprehensive observational study of lung volumes and
      elasticity in nine obese and nine normal weight subjects, seated and supine,
      during spontaneous breathing. Seated and supine total lung capacity (TLC) and
      subdivisions were measured by multibreath helium dilution method. Using balloon
      catheters, oesophageal (Poes) and gastric (Pgas) pressures were recorded.
      Transpulmonary pressure (PL) was calculated as mouth pressure (Pmouth)-Poes, and
      complete expiratory PL volume curves were measured. RESULTS: The obese group had
      a body mass index (BMI) of 46.8 (17.2) kg/m(2), and the normal group had a BMI of
      23.2 (1.6) kg/m(2) (p=0.001). Obese and normals were matched for age (p=0.233),
      gender (p=0.637) and height (p=0.094). The obese were more restricted than the
      normals (TLC 88.6 (16.9) vs 104.4 (12.3) %predicted, p=0.033; FEV1/FVC 79.6 (7.3)
      vs 82.5 (4.2) %, p=0.325), had dramatically reduced expiratory reserve volume
      (ERV 0.4 (0.4) vs 1.7 (0.6) L, p<0.001) and end-tidal functional residual
      capacity (FRC) was smaller (37.5 (6.9) vs 46.9 (4.6) %TLC, p=0.004) when seated,
      but was similar when supine (39.4 (7.7) vs 41.5 (4.3) %TLC, p=0.477). Gastric
      pressures at FRC were significantly elevated in the obese (seated 19.1 (4.7) vs
      12.1 (6.2) cm H2O, p=0.015; supine 14.3 (5.7) vs 7.1 (2.6) cm H2O, p=0.003), as
      were end-expiratory oesophageal pressures at FRC (seated 5.2 (6.9) vs -2.0 (3.5)
      cm H2O, p=0.013; supine 14.0 (8.0) vs 5.4 (3.1) cm H2O, p=0.008). BMI correlated
      with end-expiratory gastric (seated R(2)=0.43, supine R(2)=0.66, p<0.01) and
      oesophageal pressures (seated R(2)=0.51, supine R(2)=0.62, p<0.01). CONCLUSIONS:
      Obese subjects have markedly increased gastric and oesophageal pressures, both
      when upright and supine, causing dramatically reduced FRC and ERV, which
      increases work of breathing.

PMID- 24736286
TI  - Elevated plasma albumin and apolipoprotein A-I oxidation under suboptimal
      specimen storage conditions.
AB  - S-cysteinylated albumin and methionine-oxidized apolipoprotein A-I (apoA-I) have
      been posed as candidate markers of diseases associated with oxidative stress.
      Here, a dilute-and-shoot form of LC-electrospray ionization-MS requiring half a
      microliter of blood plasma was employed to simultaneously quantify the relative
      abundance of these oxidized proteoforms in samples stored at -80  degrees C, -20 
      degrees C, and room temperature and exposed to multiple freeze-thaw cycles and
      other adverse conditions in order to assess the possibility that protein
      oxidation may occur as a result of poor sample storage or handling. Samples from
      a healthy donor and a participant with poorly controlled type 2 diabetes started
      at the same low level of protein oxidation and behaved similarly; significant
      increases in albumin oxidation via S-cysteinylation were found to occur within
      hours at room temperature and days at -20  degrees C. Methionine oxidation of
      apoA-I took place on a longer time scale, setting in after albumin oxidation
      reached a plateau. Freeze-thaw cycles had a minimal effect on protein oxidation.
      In matched collections, protein oxidation in serum was the same as that in
      plasma. Albumin and apoA-I oxidation were not affected by sample headspace or the
      degree to which vials were sealed. ApoA-I, however, was unexpectedly found to
      oxidize faster in samples with lower surface-area-to-volume ratios. An initial
      survey of samples from patients with inflammatory conditions normally associated
      with elevated oxidative stress-including acute myocardial infarction and prostate
      cancer-demonstrated a lack of detectable apoA-I oxidation. Albumin S
      cysteinylation in these samples was consistent with known but relatively brief
      exposures to temperatures above -30  degrees C (the freezing point of blood
      plasma). Given their properties and ease of analysis, these oxidized proteoforms,
      once fully validated, may represent the first markers of blood plasma specimen
      integrity based on direct measurement of oxidative molecular damage that can
      occur under suboptimal storage conditions. 

PMID- 24736288
TI  - Gpr177-mediated Wnt Signaling is Required for Fungiform Placode Initiation.
AB  - Fungiform papillae are formed as patterned rows on the surface of the anterior
      tongue at early organogenesis and contain one taste bud in each papilla to form
      one of the important sensory organs. Despite the essential role of Wnt/beta
      catenin signaling in controlling the development of fungiform taste papillae, the
      universal function of Wnt ligands in the initiation of the fungiform placode has
      not been completely elucidated. Here, by Shh (Cre) -mediated oral epithelial
      deletion of Wntless (Gpr177), a regulator essential for intracellular Wnt
      trafficking, we demonstrate that an overall function of Wnts is required for
      initiation of the fungiform placode. Multiple Wnts are expressed in the tongue
      epithelium at E11.5 before initiation of the fungiform placodes. Epithelial
      Gpr177 loss-of-function, associated with reduction of canonical Wnt signaling in
      lingual epithelium as exhibited by a loss of TopGal activity and Axin2
      expression, results in the failure of fungiform placode initiation, as assessed
      by diminished expression of several taste placode molecular markers. Moreover,
      LiCl treatment of Gpr177 epithelial-deficient tongue explants at E11.5, but not
      at E12.5, restores tongue placode formation, demonstrating that Wnt ligands in
      the tongue surface prior to but not after fungiform placode initiation are
      responsible for fungiform papilla initiation. Epithelium-specific expression of
      an active beta-catenin in the Gpr177-deficient tongue leads to fungiform papillae
      generation, suggesting that an intra-epithelial response to Wnts is required for
      placode initiation. Together, these results suggest that Gpr177 controls
      epithelial initiation of the fungiform placode through signaling via epithelial
      Wnt ligands. 

PMID- 24736289
TI  - Outcomes of total hip arthroplasty in spastic patients.
AB  - Patients with spasticity and hip arthritis can present challenges to treatment.
      This investigation evaluated the effectiveness and safety of THA in patients with
      upper motor neuron disease. Twenty-seven consecutive patients with history of
      cerebral palsy (CP) or acquired spasticity (AS) underwent 30 THAs for treatment
      of hip arthritis. They were followed for an average 2.5 years (range 2.1-12.1).
      Patients with CP were more likely to require hip adductor release and hip flexor
      lengthening at the time of THA. Statistically significant improvements were made
      in Harris Hip Scores, pain scores, range of motion, ambulatory status, and the
      use ambulatory-assistive devices. There were no dislocations in this group.
      Patients with spasticity can benefit from THA in terms of pain relief and
      improved mobility with relatively low complications.

PMID- 24736290
TI  - Decreased infection rates following total joint arthroplasty in a large county
      run teaching hospital: a single surgeon's experience and possible solution.
AB  - Total joint arthroplasty is a common orthopaedic procedure producing valuable
      improvements in patient's quality of life. A dreaded complication of this
      procedure is deep seated, periprosthetic infection. This complication can lead to
      multiple reoperations and upwards of $100,000 of increased cost burden. At one
      900 bed county run teaching hospital, with a historically high infection rate in
      total joints, the total joint service was closed and restarted using a new
      protocol, dropping infection rates from 12.9% to 1.9% (P = 0.007).

PMID- 24736291
TI  - Total joint arthroplasty: trends in medicare reimbursement and implant prices.
AB  - Total joint arthroplasty (TJA) continues to be a popular target of cost control
      efforts. In order to provide a unique overview of financial trends facing TJA, we
      analyzed Medicare databases including 100% of beneficiaries, as well as industry
      surveys of implant list prices. Although there was a substantial increase in TJA
      utilization over the period 2000-2011 (+26.9%), growth has been stagnant since
      2005. New coding schemes have made complicated cases more lucrative for hospitals
      (+2.5% to 6.5% per year), while reimbursements for uncomplicated cases have
      fallen (-0.7% to -0.6%). Physician reimbursements have declined on all case types
      (-2.5% to -2.1% per year), while list prices of orthopedic implants have risen
      (+4.8% to 5.5%). These trends should be kept in mind while contemplating future
      changes to TJA payment. 

PMID- 24736292
TI  - The outcome of modified extended trochanteric osteotomy in revision THA for
      Vancouver B2/B3 periprosthetic fractures of the femur.
AB  - We hypothesised that a modified ETO in patients undergoing revision total hip
      arthroplasty (THA) for treatment of Vancouver B2/B3 peri-prosthetic fractures
      would be associated with good clinical outcomes. A retrospective review was
      conducted of 34 patients (mean age 73 years). At mean follow-up of 57 months, the
      ETO had healed in all patients. Two patients had subsidence of the femoral stem
      at two and three years postoperatively requiring revision, and one patient had a
      dislocation 3 months after surgery. The mean Harris Hip Score at the time of the
      final follow-up was 76.9 (range, 46-95); 23/34 patients had an excellent result,
      7/34 a good result, and 4/34 a poor result. We conclude that satisfactory
      outcomes can be obtained using this technique.

PMID- 24736293
TI  - Assessment of accuracy of marker ball placement in pre-operative templating for
      total hip arthroplasty.
AB  - We report the accuracy of positioning of the calibration ball in the process of
      pre-operative templating for total hip arthroplasty (THA). The ball should be
      placed in the coronal plane of the hip to provide suitable accuracy. We reviewed
      112 post-operative THA radiographs where a calibration ball had been placed. We
      templated the femoral head size of the implant after calibrating the templating
      system from the ball. The calibrated femoral head diameter was compared to the
      known prosthetic head size. A percentage error was calculated. Overall, incorrect
      placement of the calibration ball resulted in a mean percentage error in
      templating of 6.8% (median 5.7%; range 0-26%). Such error carries implications
      with the templating process and may result in incorrect component sizes, leg
      lengths and offset. 

PMID- 24736294
TI  - Detected health and well-being problems following comprehensive geriatric
      assessment during a home visit among community-dwelling older people: who
      benefits most?
AB  - BACKGROUND: Preventive home visits including comprehensive geriatric assessment
      for potentially frail older people are increasingly implemented in general
      practice. It remains unclear how to select older people who benefit most from it.
      OBJECTIVES: To determine which community-dwelling older people benefit most from
      a comprehensive geriatric assessment by a practice nurse during a home visit in
      terms of detected problems. METHODS: A cross-sectional study in 45 general
      practices in the Netherlands. Practice nurses visited 562 randomly selected older
      people (aged >= 75 years) and 1180 purposefully selected based on the following
      criteria: last visit to general practice >6 months ago; partner or child(ren)
      deceased within past 12 months; cognitive or psychosocial functioning unknown to
      GP; >=2 chronic conditions; uses >=5 medications and/or living alone. RESULTS:
      Mean age of older people was 82.50 years, 65.50% was female. More problems were
      detected among women, higher age groups, those living alone and the less educated
      (all P < 0.001). Overall, more problems were detected in purposefully selected
      older people than in randomly selected older people (P < 0.001). Selection of
      older people with >=2 chronic conditions and those using >=5 medications resulted
      in more detected problems in general (both P < 0.05). CONCLUSION: Although the
      findings are in favour of purposeful selection, observed differences in detected
      problems between the two selection procedures are relatively small. GPs should at
      least target older people with >=2 chronic conditions, using >=5 medications,
      being female, of an older age, living alone and the less educated.

PMID- 24736295
TI  - Placebo use in the UK: a qualitative study exploring GPs' views on placebo
      effects in clinical practice.
AB  - BACKGROUND: Surveys show GPs use placebos in clinical practice and reported
      prevalence rates vary widely. AIM: To explore GPs' perspectives on clinical uses
      of placebos. DESIGN AND SETTING: A web-based survey of 783 UK GPs' use of
      placebos in clinical practice. METHODS: Qualitative descriptive analysis of
      written responses ('comments') to three open-ended questions. RESULTS: Comments
      were classified into three categories: (i) defining placebos and their effects in
      general practice; (ii) ethical, societal and regulatory issues faced by doctors
      and (iii) reasons why a doctor might use placebos and placebo effects in clinical
      practice. GPs typically defined placebos as lacking something, be that adverse or
      beneficial effects, known mechanism of action and/or scientific evidence. Some
      GPs defined placebos positively as having potential to benefit patients,
      primarily through psychological mechanisms. GPs described a broad array of
      possible harms and benefits of placebo prescribing, reflecting fundamental
      bioethical principles, at the level of the individual, the doctor-patient
      relationship, the National Health Service and society. While some GPs were
      adamant that there was no place for placebos in clinical practice, others focused
      on the clinically beneficial effects of placebos in primary care. CONCLUSION:
      This study has elucidated specific costs, benefits and ethical barriers to
      placebo use as perceived by a large sample of UK GPs. Stand-alone qualitative
      work would provide a more in-depth understanding of GPs' views. Continuing
      education and professional guidance could help GPs update and contextualize their
      understanding of placebos and their clinical effects.

PMID- 24736296
TI  - What radiation dose does the FISH translocation assay measure in cases of
      incorporated radionuclides for the Southern Urals populations?
AB  - The fluorescence in situ hybridisation (FISH) technique is now well established
      for retrospective dosimetry in cases of external radiation exposure that occurred
      many years ago. However, the question remains as to whether FISH provides valid
      estimates of cumulative red bone marrow radiation doses in cases of incorporation
      of radionuclides or combined external and internal exposures. This question has
      arisen in connection with the interpretation of results of dose assessments for
      epidemiological studies of plutonium workers at the Russian Mayak plant and of
      members of the public exposed to strontium radioisotopes and external radiation
      as a result of discharges from Mayak to the Techa River. Exposures to penetrating
      external radiation result in fairly uniform irradiation of body tissues, and
      hence similar doses to all tissues, for which FISH dosimetry can provide a
      reliable measure of this whole body dose. However, intakes of radionuclides into
      the body by inhalation or ingestion may result in retention in specific organs
      and tissues, so that the distribution of dose is highly heterogeneous. For
      radionuclides emitting short-range radiations (e.g. alpha particles), this
      heterogeneity can apply to dose delivery within tissues and between cells within
      tissues. In this paper, an attempt is made to address the question of what FISH
      measures in such circumstances by considering evidence regarding the origin and
      lifetime dynamics of lymphocyte subsets in the human body in relation to the
      localised delivery of dose from the internal emitters (90)Sr and (239)Pu, which
      are of particular interest for the Southern Urals Mayak and Techa River
      populations, and for which most evidence is available in these populations. It is
      concluded that the FISH translocation assay can be usefully applied for detecting
      internal and combined external gamma and internal doses from internally deposited
      (90)Sr, albeit with fairly large uncertainties. The same may be true of (239)Pu,
      as well as other radionuclides, although much work remains to be done to
      establish dose-response relationships. 

PMID- 24736297
TI  - The Austrian radon activities on the way to the national radon action plan.
AB  - Based on the new Euratom Basic Safety Standards (BSS), all EU member states will
      be obliged to design a strategy to address long-term risks from radon exposure,
      which is laid down in the 'national radon action plan'. In Austria, the National
      Radon Centre is responsible for the development of the action plan. This paper
      presents the current and planned radon protection activities on the way to
      establish the radon action plan--like the national radon database, the definition
      of radon risk areas by improving the existing radon map, as well as strategies
      and activities to increase the radon awareness of the public and decision-makers
      and to involve the building sector. The impact of and the need for actions caused
      by the BSS requirements on the Austrian radon legislation, strategy and programme
      are discussed.

PMID- 24736298
TI  - Radon entry rate analyses using in situ tracer gas method application.
AB  - Recently, the role of energy savings in indoor air quality deterioration has been
      extensively emphasised, predominantly in the context of significant air exchange
      rate reduction as a result of home energy retrofits. In case of refurbishment of
      existing buildings, the effect of energy-efficient technologies on indoor radon
      concentration is considerably complex and has to be carefully evaluated with
      respect to radon entry rate (RER) and air exchange rate alteration. For the
      purpose of detailed analysis of radon entry pathways, the unique infiltration
      experiment has been carried out using the tracer gas (N2O) method application in
      field conditions. Significant amount of experimental works has been done to
      provide an independent assessment of RER and air-exchange rate facilitating the
      analysis of fundamental factors influencing the indoor radon variations (e.g.
      indoor-outdoor pressure difference induced by wind, stack effect, heating,
      ventilation and operation of air-conditioning systems). 

PMID- 24736299
TI  - Investigation of radiation sensitivity of some tartrate compounds.
AB  - Potential electron spin resonance (ESR) dosimetric application of different
      compounds of sodium tartrate, such as sodium tartrate dihydrate, sodium
      bitartrate monohydrate and potassium sodium tartrate tetrahydrate, was
      investigated in the range of 0.74-25 Gy. While the radiation-induced
      intermediates produced in these compounds are similar, their radiation yields are
      different. It is found that the radiation yield of sodium tartrate dihydrate is
      higher than other compounds of sodium tartrates. Comparison of the radiation
      yields were also made between well-known samples of ammonium tartrate, alanine
      and lithium formate. It is found that the radiation yields of sodium tartrate
      dihydrate, sodium bitartrate monohydrate and potassium sodium tartrate
      tetrahydrate have the values of 1.22, 0.18 and 0.13, respectively. 

PMID- 24736300
TI  - Single nucleotide polymorphisms associated with abnormal coronary microvascular
      function.
AB  - BACKGROUND: Single nucleotide polymorphisms (SNPs) are the most common source of
      genetic variation. Although microvascular pathology is associated with
      cardiovascular events, genetic phenotypes causing microvascular disease remain
      largely unknown. This study identifies sex-specific SNPs associated with coronary
      microvascular dysfunction. METHODS AND RESULTS: Six hundred and forty-three
      patients without significant obstructive coronary heart disease were enrolled,
      referred for cardiac catheterization, and underwent invasive coronary
      microcirculatory assessment. Patient data were collected from 1529 autosomal SNPs
      and seven X chromosome SNPs, which were selected to represent the variability
      from 76 candidate genes with published associations with coronary vasoreactivity,
      angiogenesis, inflammation, vascular calcification, atherosclerosis risk factors,
      female hormones, blood coagulation, or coronary heart disease. Coronary flow
      reserve (CFR) was assessed by an intracoronary injection of adenosine. Patients
      were categorized according to a CFR above or below 2.5 and were stratified by
      sex.After adjusting for age, sex, and BMI, this study shows that SNPs within
      VEGFA and CDKN2B-AS1 are associated with abnormal CFR (P<0.005). SNPs within
      MYH15, VEGFA, and NT5E are associated with abnormal CFR in men. No SNPs were
      associated with abnormal CFR in women. CONCLUSION: Genetic variations within
      defined regions of VEGFA and CDKN2B-AS1 genes are associated with coronary
      microvascular dysfunction. Furthermore, sex-specific allelic variants within
      MYH15, VEGFA, and NT5E are associated with an increased risk of coronary
      microvascular dysfunction in men.

PMID- 24736301
TI  - Long-term comparison of sirolimus-eluting and bare-metal stents in ST-segment
      elevation myocardial infarction.
AB  - OBJECTIVES: We aimed to investigate, in patients with ST-segment elevation
      myocardial infarction (STEMI), whether the previously reported clinical benefits
      of sirolimus-eluting stent(s) (SES) in terms of reducing a major adverse cardiac
      and cerebrovascular event (MACCE) compared with bare-metal stent(s) (BMS) were
      maintained over a 5-year time period. BACKGROUND: In the prospective single
      centre randomized DEBATER trial, SES significantly reduced the rate of MACCE in
      STEMI patients within 1 year compared with BMS, mainly driven by a reduction of
      target lesion revascularization. Randomized data on the long-term safety and
      efficacy of SES in STEMI patients are conflicting and limited. PATIENTS AND
      METHODS: Between January 2006 and May 2008, a total of 907 STEMI patients were
      randomized to receive SES or BMS. The primary endpoint was MACCE defined as the
      composite of death, myocardial infarction, stroke, repeat revascularization and
      bleeding. Five-year follow-up data were collected by reviewing hospital records,
      telephone calls and a written questionnaire. RESULTS: At 5 years, the rate of
      MACCE between the SES group and the BMS group was no longer significantly
      different (33.3 vs. 39.3%, P=0.12). The cumulative incidence of death and
      myocardial infarction was similar in both groups (11.0 vs. 9.7%, P=0.51). Repeat
      revascularization was performed in 21.1 and 25.8% of patients, respectively
      (P=0.12). The rate of very late stent thrombosis (1-5 years of follow-up) was
      very low in both groups (2.0 vs. 0.7%, P=0.12). CONCLUSION: The benefits of SES
      in STEMI patients in terms of reducing MACCE faded over time. We found no safety
      concerns in terms of SES in the long term, with extremely low rates of very late
      stent thrombosis.

PMID- 24736302
TI  - Shared environmental effects on multiple sclerosis susceptibility: conflicting
      evidence from twin studies.

PMID- 24736303
TI  - Diffusion tensor imaging analysis of sequential spreading of disease in
      amyotrophic lateral sclerosis confirms patterns of TDP-43 pathology.
AB  - Diffusion tensor imaging can identify amyotrophic lateral sclerosis-associated
      patterns of brain alterations at the group level. Recently, a neuropathological
      staging system for amyotrophic lateral sclerosis has shown that amyotrophic
      lateral sclerosis may disseminate in a sequential regional pattern during four
      disease stages. The objective of the present study was to apply a new
      methodological diffusion tensor imaging-based approach to automatically analyse
      in vivo the fibre tracts that are prone to be involved at each neuropathological
      stage of amyotrophic lateral sclerosis. Two data samples, consisting of 130
      diffusion tensor imaging data sets acquired at 1.5 T from 78 patients with
      amyotrophic lateral sclerosis and 52 control subjects; and 55 diffusion-tensor
      imaging data sets at 3.0 T from 33 patients with amyotrophic lateral sclerosis
      and 22 control subjects, were analysed by a tract of interest-based fibre
      tracking approach to analyse five tracts that become involved during the course
      of amyotrophic lateral sclerosis: the corticospinal tract (stage 1); the
      corticorubral and the corticopontine tracts (stage 2); the corticostriatal
      pathway (stage 3); the proximal portion of the perforant path (stage 4); and two
      reference pathways. The statistical analyses of tracts of interest showed
      differences between patients with amyotrophic lateral sclerosis and control
      subjects for all tracts. The significance level of the comparisons at the group
      level was lower, the higher the disease stage with corresponding involved fibre
      tracts. Both the clinical phenotype as assessed by the amyotrophic lateral
      sclerosis functional rating scale-revised and disease duration correlated
      significantly with the resulting staging scheme. In summary, the tract of
      interest-based technique allowed for individual analysis of predefined tract
      structures, thus making it possible to image in vivo the disease stages in
      amyotrophic lateral sclerosis. This approach can be used not only for individual
      clinical work-up purposes, but enlarges the spectrum of potential non-invasive
      surrogate markers as a neuroimaging-based read-out for amyotrophic lateral
      sclerosis studies within a clinical context. 

PMID- 24736304
TI  - Congenital mirror movements: lack of decussation of pyramids.

PMID- 24736305
TI  - Chasing central nervous system plasticity: the brainstem's contribution to
      locomotor recovery in rats with spinal cord injury.
AB  - Anatomical plasticity such as fibre growth and the formation of new connections
      in the cortex and spinal cord is one known mechanism mediating functional
      recovery after damage to the central nervous system. Little is known about
      anatomical plasticity in the brainstem, which contains key locomotor regions. We
      compared changes of the spinal projection pattern of the major descending systems
      following a cervical unilateral spinal cord hemisection in adult rats. As in
      humans (Brown-Sequard syndrome), this type of injury resulted in a permanent loss
      of fine motor control of the ipsilesional fore- and hindlimb, but for basic
      locomotor functions substantial recovery was observed. Antero- and retrograde
      tracings revealed spontaneous changes in spinal projections originating from the
      reticular formation, in particular from the contralesional gigantocellular
      reticular nucleus: more reticulospinal fibres from the intact hemicord crossed
      the spinal midline at cervical and lumbar levels. The intact-side rubrospinal
      tract showed a statistically not significant tendency towards an increased number
      of midline crossings after injury. In contrast, the corticospinal and the
      vestibulospinal tract, as well as serotonergic projections, showed little or no
      side-switching in this lesion paradigm. Spinal adaptations were accompanied by
      modifications at higher levels of control including side-switching of the input
      to the gigantocellular reticular nuclei from the mesencephalic locomotor region.
      Electrolytic microlesioning of one or both gigantocellular reticular nuclei in
      behaviourally recovered rats led to the reappearance of the impairments observed
      acutely after the initial injury showing that anatomical plasticity in defined
      brainstem motor networks contributes significantly to functional recovery after
      injury of the central nervous system. 

PMID- 24736306
TI  - Time for tau.

PMID- 24736307
TI  - Reply: Syncope and electroencephalography.

PMID- 24736309
TI  - A novel missense mutation confirms ATL3 as a gene for hereditary sensory
      neuropathy type 1.

PMID- 24736308
TI  - Uncovering the role of the insula in non-motor symptoms of Parkinson's disease.
AB  - Patients with Parkinson's disease experience a range of non-motor symptoms,
      including cognitive impairment, behavioural changes, somatosensory and autonomic
      disturbances. The insula, which was once thought to be primarily a limbic
      cortical structure, is now known to be highly involved in integrating
      somatosensory, autonomic and cognitive-affective information to guide behaviour.
      Thus, it acts as a central hub for processing relevant information related to the
      state of the body as well as cognitive and mood states. Despite these crucial
      functions, the insula has been largely overlooked as a potential key region in
      contributing to non-motor symptoms of Parkinson's disease. The insula is affected
      in Parkinson's disease by alpha-synuclein deposition, disruptions in normal
      neurotransmitter function, alterations in connectivity as well as metabolic and
      structural changes. Although research focusing on the role of the insula in
      Parkinson's disease is scarce, there is evidence from neuroimaging studies
      linking the insula to cognitive decline, behavioural abnormalities and
      somatosensory disturbances. Here, we review imaging studies that provide insight
      into the potential role of the insula in Parkinson's disease non-motor symptoms. 

PMID- 24736310
TI  - Fialuridine induces acute liver failure in chimeric TK-NOG mice: a model for
      detecting hepatic drug toxicity prior to human testing.
AB  - BACKGROUND: Seven of 15 clinical trial participants treated with a nucleoside
      analogue (fialuridine [FIAU]) developed acute liver failure. Five treated
      participants died, and two required a liver transplant. Preclinical toxicology
      studies in mice, rats, dogs, and primates did not provide any indication that
      FIAU would be hepatotoxic in humans. Therefore, we investigated whether FIAU
      induced liver toxicity could be detected in chimeric TK-NOG mice with humanized
      livers. METHODS AND FINDINGS: Control and chimeric TK-NOG mice with humanized
      livers were treated orally with FIAU 400, 100, 25, or 2.5 mg/kg/d. The response
      to drug treatment was evaluated by measuring plasma lactate and liver enzymes, by
      assessing liver histology, and by electron microscopy. After treatment with FIAU
      400 mg/kg/d for 4 d, chimeric mice developed clinical and serologic evidence of
      liver failure and lactic acidosis. Analysis of liver tissue revealed steatosis in
      regions with human, but not mouse, hepatocytes. Electron micrographs revealed
      lipid and mitochondrial abnormalities in the human hepatocytes in FIAU-treated
      chimeric mice. Dose-dependent liver toxicity was detected in chimeric mice
      treated with FIAU 100, 25, or 2.5 mg/kg/d for 14 d. Liver toxicity did not
      develop in control mice that were treated with the same FIAU doses for 14 d. In
      contrast, treatment with another nucleotide analogue (sofosbuvir 440 or 44
      mg/kg/d po) for 14 d, which did not cause liver toxicity in human trial
      participants, did not cause liver toxicity in mice with humanized livers.
      CONCLUSIONS: FIAU-induced liver toxicity could be readily detected using chimeric
      TK-NOG mice with humanized livers, even when the mice were treated with a FIAU
      dose that was only 10-fold above the dose used in human participants. The
      clinical features, laboratory abnormalities, liver histology, and ultra
      structural changes observed in FIAU-treated chimeric mice mirrored those of FIAU
      treated human participants. The use of chimeric mice in preclinical toxicology
      studies could improve the safety of candidate medications selected for testing in
      human participants. Please see later in the article for the Editors' Summary.

PMID- 24736311
TI  - Targeted disruption of beta-arrestin 2-mediated signaling pathways by aptamer
      chimeras leads to inhibition of leukemic cell growth.
AB  - beta-arrestins, ubiquitous cellular scaffolding proteins that act as signaling
      mediators of numerous critical cellular pathways, are attractive therapeutic
      targets because they promote tumorigenesis in several tumor models. However,
      targeting scaffolding proteins with traditional small molecule drugs has been
      challenging. Inhibition of beta-arrestin 2 with a novel aptamer impedes multiple
      oncogenic signaling pathways simultaneously. Additionally, delivery of the beta
      arrestin 2-targeting aptamer into leukemia cells through coupling to a recently
      described cancer cell-specific delivery aptamer, inhibits multiple beta-arrestin
      mediated signaling pathways known to be required for chronic myelogenous leukemia
      (CML) disease progression, and impairs tumorigenic growth in CML patient samples.
      The ability to target scaffolding proteins such as beta-arrestin 2 with RNA
      aptamers may prove beneficial as a therapeutic strategy. HIGHLIGHTS: An RNA
      aptamer inhibits beta-arrestin 2 activity.Inhibiting beta-arrestin 2 impedes
      multiple tumorigenic pathways simultaneously.The therapeutic aptamer is delivered
      to cancer cells using a cell-specific DNA aptamer.Targeting beta-arrestin 2
      inhibits tumor progression in CML models and patient samples.

PMID- 24736312
TI  - Comparison of efficacy of the disease-specific LOX1- and constitutive
      cytomegalovirus-promoters in expressing interleukin 10 through adeno-associated
      virus 2/8 delivery in atherosclerotic mice.
AB  - The development of gene therapy vectors for treating diseases of the
      cardiovascular system continues at a steady pace. Moreover, in the field of gene
      therapy the utility of "disease-specific promoters" has strong appeal. Many
      therapeutic genes, including transforming growth factor beta 1 or interleukin 10,
      are associated to adverse effects. The use of a disease-specific promoter might
      minimize toxicity. The lectin-like oxidized low density lipoprotein receptor 1 is
      a marker of cardiovascular disease and a potential therapeutic target. The lectin
      like oxidized low density lipoprotein receptor 1 is known to be up-regulated
      early during disease onset in a number of cell types at the sites where the
      disease will be clinically evident. In this study an adeno-associated virus-2 DNA
      vector (AAV2) using the AAV8 capsid, and containing the full length The lectin
      like oxidized low density lipoprotein receptor 1 promoter, was generated and
      assayed for its ability to express human interleukin 10 in low density
      lipoprotein receptor knockout mice on high cholesterol diet. The cytomegalovirus
      early promoter was used for comparison in a similarly structured vector. The two
      promoters were found to have equal efficacy in reducing atherogenesis as measured
      by aortic systolic blood velocity, aortic cross sectional area, and aortic wall
      thickness. This is the first head-to-head comparison of a constitutive with a
      disease-specific promoter in a therapeutic context. These data strongly suggest
      that the use of a disease-specific promoter is appropriate for therapeutic gene
      delivery. 

PMID- 24736313
TI  - Comparing continuous and intermittent exercise: an "isoeffort" and "isotime"
      approach.
AB  - The present study proposes an alternative way of comparing performance and acute
      physiological responses to continuous exercise with those of intermittent
      exercise, ensuring similar between-protocol overall effort (isoeffort) and the
      same total duration of exercise (isotime). This approach was expected to overcome
      some drawbacks of traditional methods of comparison. Fourteen competitive
      cyclists (20+/-3 yrs) performed a preliminary incremental test and four
      experimental 30-min self-paced protocols, i.e. one continuous and three passive
      recovery intermittent exercise protocols with different work-to-rest ratios (2 =
      40?20s, 1 = 30?30s and 0.5 = 20?40s). A "maximal session effort" prescription was
      adopted for this experimental design. As expected, a robust perceived exertion
      template was observed irrespective of exercise protocol. Similar between-protocol
      pacing strategies further support the use of the proposed approach in competitive
      cyclists. Total work, oxygen uptake and heart rate mean values were significantly
      higher (P<0.05) in the continuous compared to intermittent protocols, while
      lactate values were lower. Manipulating the work-to-rest ratio in intermittent
      exercise, total work, oxygen uptake and heart rate mean values decreased with the
      decrease in the work-to-rest ratio, while lactate values increased. Despite this
      complex physiological picture, all protocols showed similar ventilatory responses
      and a nearly perfect relationship between respiratory frequency and perceived
      exertion. In conclusion, our data indicate that overall effort and total duration
      of exercise are two critical parameters that should both be controlled when
      comparing continuous with intermittent exercise. On an isoeffort and isotime
      basis, the work-to-rest ratio manipulation affects physiological responses in a
      different way from what has been reported in literature with traditional methods
      of comparison. Finally, our data suggest that during intermittent exercise
      respiratory frequency reflects physiological strain better than oxygen uptake,
      heart rate and blood lactate.

PMID- 24736314
TI  - The fermentation of polydextrose in the large intestine and its beneficial
      effects.
AB  - Polydextrose is a randomly bonded glucose polymer with a highly branched and
      complex structure. It resists digestion in the upper gastrointestinal tract and
      is partially fermented in the large intestine by the colonic microbes. Due to its
      complex structure, a plethora of microbes is required for the catabolism of
      polydextrose and this process occurs slowly. This gradual fermentation of
      polydextrose gives rise to moderate amounts of fermentation products, such as
      short chain fatty acids and gas. The production of these metabolites continues in
      the distal part of the colon, which is usually considered to be depleted of
      saccharolytic fermentation substrates. The fermentation of polydextrose modifies
      the composition of the microbiota in the colon, and has been shown to impact
      appetite and satiety in humans and improve the gastrointestinal function. The
      purpose of this short review is to summarise the in vitro, in vivo and human
      studies investigating the fermentation properties of polydextrose in the large
      intestine.

PMID- 24736315
TI  - Changes in mouse gastrointestinal microbial ecology with ingestion of kale.
AB  - Kale, a cultivar of Brassica oleracea, has attracted a great deal of attention
      because of its health-promoting effects, which are thought to be exerted through
      modulation of the intestinal microbiota. The present study was performed to
      investigate the effects of kale ingestion on the gastrointestinal microbial
      ecology of mice. 21 male C57BL/6J mice were divided into three groups and housed
      in a specific pathogen-free facility. The animals were fed either a control diet
      or experimental diets supplemented with different commercial kale products for 12
      weeks. Contents of the caecum and colon of the mice were processed for the
      determination of active bacterial populations by a bacterial rRNA-based
      quantification method and short-chain fatty acids by HPLC. rRNAs of Bacteroides
      Prevotella, the Clostridium coccoides-Eubacterium rectale group, and Clostridium
      leptum subgroup constituted the major fraction of microbiota regardless of the
      composition of the diet. The ratio of Firmicutes to Bacteroidetes was higher in
      the colon samples of one of the kale diet groups than in the control. The colonic
      butyrate level was also higher with the kale-supplemented diet. Overall, the
      ingestion of kale tended to either increase or decrease the activity of specific
      bacterial groups in the mouse gastrointestinal tract, however, the effect might
      vary depending on the nutritional composition.

PMID- 24736317
TI  - BMJ Awards 2014. Diabetes Team of the Year: adaptable and supportive.

PMID- 24736316
TI  - Experimental orthotopic transplantation of a tissue-engineered oesophagus in
      rats.
AB  - A tissue-engineered oesophageal scaffold could be very useful for the treatment
      of pediatric and adult patients with benign or malignant diseases such as
      carcinomas, trauma or congenital malformations. Here we decellularize rat
      oesophagi inside a perfusion bioreactor to create biocompatible biological rat
      scaffolds that mimic native architecture, resist mechanical stress and induce
      angiogenesis. Seeded allogeneic mesenchymal stromal cells spontaneously
      differentiate (proven by gene-, protein and functional evaluations) into
      epithelial- and muscle-like cells. The reseeded scaffolds are used to
      orthotopically replace the entire cervical oesophagus in immunocompetent rats.
      All animals survive the 14-day study period, with patent and functional grafts,
      and gain significantly more weight than sham-operated animals. Explanted grafts
      show regeneration of all the major cell and tissue components of the oesophagus
      including functional epithelium, muscle fibres, nerves and vasculature. We
      consider the presented tissue-engineered oesophageal scaffolds a significant step
      towards the clinical application of bioengineered oesophagi.

PMID- 24736318
TI  - Development and validation of a prediction model for tube feeding dependence
      after curative (chemo-) radiation in head and neck cancer.
AB  - BACKGROUND: Curative radiotherapy or chemoradiation for head and neck cancer
      (HNC) may result in severe acute and late side effects, including tube feeding
      dependence. The purpose of this prospective cohort study was to develop a
      prediction model for tube feeding dependence 6 months (TUBEM6) after curative
      (chemo-) radiotherapy in HNC patients. PATIENTS AND METHODS: Tube feeding
      dependence was scored prospectively. To develop the multivariable model, a group
      LASSO analysis was carried out, with TUBEM6 as the primary endpoint (n = 427).
      The model was then validated in a test cohort (n = 183). The training cohort was
      divided into three groups based on the risk of TUBEM6 to test whether the model
      could be extrapolated to later time points (12, 18 and 24 months). RESULTS: Most
      important predictors for TUBEM6 were weight loss prior to treatment, advanced T
      stage, positive N-stage, bilateral neck irradiation, accelerated radiotherapy and
      chemoradiation. Model performance was good, with an Area under the Curve of 0.86
      in the training cohort and 0.82 in the test cohort. The TUBEM6-based risk groups
      were significantly associated with tube feeding dependence at later time points
      (p<0.001). CONCLUSION: We established an externally validated predictive model
      for tube feeding dependence after curative radiotherapy or chemoradiation, which
      can be used to predict TUBEM6.

PMID- 24736320
TI  - Peristaltic transport of Carreau-Yasuda fluid in a curved channel with slip
      effects.
AB  - The wide occurrence of peristaltic pumping should not be surprising at all since
      it results physiologically from neuro-muscular properties of any tubular smooth
      muscle. Of special concern here is to predict the rheological effects on the
      peristaltic motion in a curved channel. Attention is focused to develop and
      simulate a nonlinear mathematical model for Carreau-Yasuda fluid. The progressive
      wave front of peristaltic flow is taken sinusoidal (expansion/contraction type).
      The governing problem is challenge since it has nonlinear differential equation
      and nonlinear boundary conditions even in the long wavelength and low Reynolds
      number regime. Numerical solutions for various flow quantities of interest are
      presented. Comparison for different flow situations is also made. Results of
      physical quantities are interpreted with particular emphasis to rheological
      characteristics. 

PMID- 24736319
TI  - Network analysis of inflammatory genes and their transcriptional regulators in
      coronary artery disease.
AB  - Network analysis is a novel method to understand the complex pathogenesis of
      inflammation-driven atherosclerosis. Using this approach, we attempted to
      identify key inflammatory genes and their core transcriptional regulators in
      coronary artery disease (CAD). Initially, we obtained 124 candidate genes
      associated with inflammation and CAD using Polysearch and CADgene database for
      which protein-protein interaction network was generated using STRING 9.0 (Search
      Tool for the Retrieval of Interacting Genes) and visualized using Cytoscape v
      2.8.3. Based on betweenness centrality (BC) and node degree as key topological
      parameters, we identified interleukin-6 (IL-6), vascular endothelial growth
      factor A (VEGFA), interleukin-1 beta (IL-1B), tumor necrosis factor (TNF) and
      prostaglandin-endoperoxide synthase 2 (PTGS2) as hub nodes. The backbone network
      constructed with these five hub genes showed 111 nodes connected via 348 edges,
      with IL-6 having the largest degree and highest BC. Nuclear factor kappa B1
      (NFKB1), signal transducer and activator of transcription 3 (STAT3) and JUN were
      identified as the three core transcription factors from the regulatory network
      derived using MatInspector. For the purpose of validation of the hub genes, 97
      test networks were constructed, which revealed the accuracy of the backbone
      network to be 0.7763 while the frequency of the hub nodes remained largely
      unaltered. Pathway enrichment analysis with ClueGO, KEGG and REACTOME showed
      significant enrichment of six validated CAD pathways - smooth muscle cell
      proliferation, acute-phase response, calcidiol 1-monooxygenase activity, toll
      like receptor signaling, NOD-like receptor signaling and adipocytokine signaling
      pathways. Experimental verification of the above findings in 64 cases and 64
      controls showed increased expression of the five candidate genes and the three
      transcription factors in the cases relative to the controls (p<0.05). Thus,
      analysis of complex networks aid in the prioritization of genes and their
      transcriptional regulators in complex diseases. 

PMID- 24736321
TI  - Surgeons' exposure to radiation in single- and multi-level minimally invasive
      transforaminal lumbar interbody fusion; a prospective study.
AB  - Although minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) has
      widely been developed in patients with lumbar diseases, surgeons risk exposure to
      fluoroscopic radiation. However, to date, there is no studies quantifying the
      effective dose during MIS-TLIF procedure, and the radiation dose distribution is
      still unclear. In this study, the surgeons' radiation doses at 5 places on the
      bodies were measured and the effective doses were assessed during 31 consecutive
      1- to 3-level MIS-TLIF surgeries. The operating surgeon, assisting surgeon, and
      radiological technologist wore thermoluminescent dosimeter on the unshielded
      thyroid, chest, genitals, right middle finger, and on the chest beneath a lead
      apron. The doses at the lens and the effective doses were also calculated. Mean
      fluoroscopy times were 38.7, 53.1, and 58.5 seconds for 1, 2, or 3 fusion levels,
      respectively. The operating surgeon's mean exposures at the lens, thyroid, chest,
      genitals, finger, and the chest beneath the shield, respectively, were 0.07,
      0.07, 0.09, 0.14, 0.32, and 0.05 mSv in 1-level MIS-TLIF; 0.07, 0.08, 0.09, 0.18,
      0.34, and 0.05 mSv in 2-level; 0.08, 0.09, 0.14, 0.15, 0.36, and 0.06 mSv in 3
      level; and 0.07, 0.08, 0.10, 0.15, 0.33, and 0.05 mSv in all cases. Mean dose at
      the operating surgeon's right finger was significantly higher than other
      measurements parts (P<0.001). The operating surgeon's effective doses (0.06,
      0.06, and 0.07 mSv for 1, 2, and 3 fusion levels) were low, and didn't differ
      significantly from those of the assisting surgeon or radiological technologist.
      Revision MIS-TLIF was not associated with higher surgeons' radiation doses
      compared to primary MIS-TLIF. There were significantly higher surgeons' radiation
      doses in over-weight than in normal-weight patients. The surgeons' radiation
      exposure during MIS-TLIF was within the safe level by the International
      Commission on Radiological Protection's guidelines. The accumulated radiation
      exposure, especially to surgeon's hands, should be carefully monitored.

PMID- 24736322
TI  - Estimation of the exposure of the UK population to the bovine spongiform
      encephalopathy agent through dietary intake during the period 1980 to 1996.
AB  - Although the incidence of variant Creutzfeldt-Jakob disease (vCJD) has declined
      to 1 since 2012 in the UK, uncertainty remains regarding possible future cases
      and the size of the subclinical population that may cause secondary transmission
      of the disease through blood transfusion. Estimating the number of individuals
      who were exposed to the bovine spongiform encephalopathy (BSE) infectious agent
      and may be susceptible to vCJD will help to clarify related public health
      concerns and plan strategies. In this paper, we explore this estimate by
      describing the probability of potential exposure due to dietary intake throughout
      the BSE epidemic period from 1980 to 1996 as a stochastic Poisson process. We
      estimate the age- and gender-specific exposure intensities in food categories of
      beef and beef-containing dishes, burgers and kebabs, pies, and sausages,
      separating the two periods of 1980-1989 and 1990-1996 due to the specified bovine
      offal legislation of 1989. The estimated total number of (living) exposed
      individuals during each period is 5,089,027 (95% confidence interval [CI]
      4,514,963-6,410,317), which was obtained by multiplying the population size of
      different birth cohorts by the probability of exposure via dietary intake and the
      probability of survival until the end of 2013. The estimated number is
      approximately doubled, assuming a contamination rate of [Formula: see text].
      Among those individuals estimated, 31,855 (95% CI 26,849-42,541) are susceptible
      to infection. We also examined the threshold hypothesis by fitting an extreme
      value distribution to the estimated infectious dose of the exposed individuals
      and obtained a threshold estimate of 13.7 bID50 (95% CI 6.6-26.2 bID50)
      (Weibull). The results provide useful information on potential carriers of prion
      disease who may pose a threat of infection via blood transfusion and thus provide
      insight into the likelihood of new incidents of vCJD occurring in the future. 

PMID- 24736323
TI  - Disease resistance in Atlantic salmon (Salmo salar): coinfection of the
      intracellular bacterial pathogen Piscirickettsia salmonis and the sea louse
      Caligus rogercresseyi.
AB  - BACKGROUND: Naturally occurring coinfections of pathogens have been reported in
      salmonids, but their consequences on disease resistance are unclear. We
      hypothesized that 1) coinfection of Caligus rogercresseyi reduces the resistance
      of Atlantic salmon to Piscirickettsia salmonis; and 2) coinfection resistance is
      a heritable trait that does not correlate with resistance to a single infection.
      METHODOLOGY: In total, 1,634 pedigreed Atlantic salmon were exposed to a single
      infection (SI) of P. salmonis (primary pathogen) or coinfection with C.
      rogercresseyi (secondary pathogen). Low and high level of coinfection were
      evaluated (LC = 44 copepodites per fish; HC = 88 copepodites per fish). Survival
      and quantitative genetic analyses were performed to determine the resistance to
      the single infection and coinfections. MAIN FINDINGS: C. rogercresseyi
      significantly increased the mortality in fish infected with P. salmonis (SI
      mortality = 251/545; LC mortality = 544/544 and HC mortality = 545/545).
      Heritability estimates for resistance to P. salmonis were similar and of medium
      magnitude in all treatments (h2SI = 0.23 +/- 0.07; h2LC = 0.17 +/- 0.08; h2HC =
      0.24 +/- 0.07). A large and significant genetic correlation with regard to
      resistance was observed between coinfection treatments (rg LC-HC = 0.99 +/- 0.01)
      but not between the single and coinfection treatments (rg SI-LC = -0.14 +/- 0.33;
      rg SI-HC = 0.32 +/- 0.34). CONCLUSIONS/SIGNIFICANCE: C. rogercresseyi, as a
      secondary pathogen, reduces the resistance of Atlantic salmon to the pathogen P.
      salmonis. Resistance to coinfection of Piscirickettsia salmonis and Caligus
      rogercresseyi in Atlantic salmon is a heritable trait. The absence of a genetic
      correlation between resistance to a single infection and resistance to
      coinfection indicates that different genes control these processes. Coinfection
      of different pathogens and resistance to coinfection needs to be considered in
      future research on salmon farming, selective breeding and conservation.

PMID- 24736325
TI  - In vivo investigation of homocysteine metabolism to polyamines by high-resolution
      accurate mass spectrometry and stable isotope labeling.
AB  - Polyamines are essential polycations, playing important roles in mammalian
      physiology. Theoretically, the involvement of homocysteine in polyamine synthesis
      via S-adenosylmethionine is possible; however, to our knowledge, it has not been
      established experimentally. Here, we propose an original approach for
      investigation of homocysteine metabolites in an animal model. The method is based
      on the combination of isotope-labeled homocysteine supplementation and high
      resolution accurate mass spectrometry analysis. Structural identity of the
      isotope-labeled metabolites was confirmed by accurate mass measurements of
      molecular and fragment ions and comparison of the retention times and tandem mass
      spectrometry fragmentation patterns. Isotope-labeled methionine, spermidine, and
      spermine were detected in all investigated plasma and tissue samples. The
      induction of moderate hyperhomocysteinemia leads to an alteration in polyamine
      levels in a different manner. The involvement of homocysteine in polyamine
      synthesis and modulation of polyamine levels could contribute to a better
      understanding of the mechanisms connected with homocysteine toxicity. 

PMID- 24736324
TI  - Long-term behavioral programming induced by peripuberty stress in rats is
      accompanied by GABAergic-related alterations in the Amygdala.
AB  - Stress during childhood and adolescence is a risk factor for psychopathology.
      Alterations in gamma-aminobutyric acid (GABA), the main inhibitory
      neurotransmitter in the brain, have been found following stress exposure and fear
      experiences and are often implicated in anxiety and mood disorders. Abnormal
      amygdala functioning has also been detected following stress exposure and is also
      implicated in anxiety and social disorders. However, the amygdala is not a
      unitary structure; it includes several nuclei with different functions and little
      is known on the potential differences the impact of early life stress may have on
      this system within different amygdaloid nuclei. We aimed here to evaluate
      potential regional differences in the expression of GABAergic-related markers
      across several amygdaloid nuclei in adult rats subjected to a peripuberty stress
      protocol that leads to enhanced basal amygdala activity and psychopathological
      behaviors. More specifically, we investigated the protein expression levels of
      glutamic acid decarboxylase (GAD; the principal synthesizing enzyme of GABA) and
      of GABA-A receptor subunits alpha2 and alpha3. We found reduced GAD and GABA-A
      alpha3, but not alpha2, subunit protein levels throughout all the amygdala nuclei
      examined (lateral, basolateral, basomedial, medial and central) and increased
      anxiety-like behaviors and reduced sociability in peripubertally stressed
      animals. Our results identify an enduring inhibition of the GABAergic system
      across the amygdala following exposure to early adversity. They also highlight
      the suitability of the peripuberty stress model to investigate the link between
      treatments targeting the dysfunctional GABAergic system in specific amygdala
      nuclei and recovery of specific stress-induced behavioral dysfunctions. 

PMID- 24736327
TI  - Potential of 18F-FDG-PET and PET/CT in nonmalignant pulmonary disorders: much
      more than currently perceived? Making the case from experience gained in the
      Indian scenario.

PMID- 24736326
TI  - Outbreak of avian malaria associated to multiple species of Plasmodium in
      magellanic penguins undergoing rehabilitation in southern Brazil.
AB  - Avian malaria is a mosquito-borne disease caused by Plasmodium spp. Avian
      plasmodia are recognized conservation-threatening pathogens due to their
      potential to cause severe epizootics when introduced to bird populations with
      which they did not co-evolve. Penguins are considered particularly susceptible,
      as outbreaks in captive populations will often lead to high morbidity and rapid
      mortality. We used a multidisciplinary approach to investigate an outbreak of
      avian malaria in 28 Magellanic penguins (Spheniscus magellanicus) at a
      rehabilitation center during summer 2009 in Florianopolis, Brazil. Hemosporidian
      infections were identified by microscopic and molecular characterization in 64%
      (18/28) of the penguins, including Plasmodium (Haemamoeba) tejerai, Plasmodium
      (Huffia) elongatum, a Plasmodium (Haemamoeba) sp. lineage closely related to
      Plasmodium cathemerium, and a Haemoproteus (Parahaemoproteus) sp. lineage closely
      related to Haemoproteus syrnii. P. tejerai played a predominant role in the
      studied outbreak and was identified in 72% (13/18) of the hemosporidian-infected
      penguins, and in 89% (8/9) of the penguins that died, suggesting that this is a
      highly pathogenic parasite for penguins; a detailed description of tissue meronts
      and lesions is provided. Mixed infections were identified in three penguins, and
      involved P. elongatum and either P. tejerai or P. (Haemamoeba) sp. that were
      compatible with P. tejerai but could not be confirmed. In total, 32% (9/28)
      penguins died over the course of 16 days despite oral treatment with chloroquine
      followed by sulfadiazine-trimethoprim. Hemosporidian infections were considered
      likely to have occurred during rehabilitation, probably from mosquitoes infected
      while feeding on local native birds, whereas penguin-mosquito-penguin
      transmission may have played a role in later stages of the outbreak. Considering
      the seasonality of the infection, rehabilitation centers would benefit from
      narrowing their efforts to prevent avian malaria outbreaks to the penguins that
      are maintained throughout summer.

PMID- 24736328
TI  - Hybrid imaging using low-dose, localizing computed tomography enhances lesion
      localization in renal hyperparathyroidism.
AB  - BACKGROUND: Preoperative localization of parathyroid lesions is potentially
      beneficial in renal patients with hyperparathyroidism. The aim of this study was
      to determine the localizing value of hybrid single-photon emission computed
      tomography combined with low-dose x-ray computed tomography (SPECT/LDCT) compared
      with SPECT alone and whether the LDCT improved reader confidence. PATIENTS AND
      METHODS: A retrospective study examined parathyroid scintigraphy results of
      patients previously referred with a diagnosis of renal hyperparathyroidism. All
      patients underwent planar scintigraphy using technetium-99m (Tc)-pertechnetate,
      which was immediately followed with Tc-sestamibi and SPECT/LDCT ~60 min after
      sestamibi injection and a delayed static image to assess differential washout.
      Planar subtraction images were generated. Two nuclear physicians, assisted by a
      radiologist, reported on planar+SPECT images followed by planar+SPECT/LDCT
      images. RESULTS: Thirty-seven patients (males: 21; females: 16) were included
      (mean age 39 years, range: 23.9-55.5). Mean creatinine level was 878 MUmol/l (109
      1839), mean corrected calcium level was 2.42 mmol/l (1.77-3.64), and median
      parathyroid hormone level was 156.2 pmol/l (2.4 to >201). Twenty-three patients
      had positive planar and SPECT results (46 lesions), six had positive planar
      results only, and eight had negative scintigraphy results. In the patients with
      positive planar and SPECT results, 35 lesions were classified as eutopic and 11
      as ectopic. After the addition of LDCT, localization of five eutopic lesions (on
      SPECT) was amended to ectopic locations (on SPECT/LDCT), principally by
      identifying posteriorly situated glands. The addition of LDCT led to increased
      confidence in localization in all cases. CONCLUSION: Compared with SPECT alone,
      SPECT/LDCT is beneficial in preoperative localization of lesions in renal
      hyperparathyroidism.

PMID- 24736329
TI  - Chronic recurrent multifocal osteomyelitis: typical patterns of bone involvement
      in whole-body bone scintigraphy.
AB  - Chronic recurrent multifocal osteomyelitis (CRMO) is an autoinflammatory bone
      disease of unknown etiology. It affects children and adolescents predominantly
      and occurs mostly in the female population. It is characterized by the insidious
      onset of pain and swelling, with a fluctuating clinical course of relapses and
      remissions. Typically, several bones are affected, either synchronously or
      metachronously, and bilateral involvement is common. CRMO most commonly affects
      the metaphysis of long bones, especially the tibia, femur, and clavicle. The
      spine, pelvis, ribs, sternum, and mandible may also be affected. Although lesions
      are mostly multiple, patients may present with a single symptomatic focus.
      Radiographic findings may be negative early in the course of the disease. Bone
      scintigraphy is useful in determining the presence of abnormality and the extent
      of disease. The imaging and clinical features of CRMO overlap with those of
      infectious osteomyelitis, bone malignancy, and inflammatory arthritis.
      Nonetheless, CRMO can be confidently diagnosed with the recognition of typical
      imaging patterns in the appropriate clinical setting. This article reviews
      imaging findings with special emphasis on bone scintigraphy and specific disease
      sites. 

PMID- 24736330
TI  - Urine bile acids relate to glucose control in patients with type 2 diabetes
      mellitus and a body mass index below 30 kg/m2.
AB  - Bile acids are important endocrine signalling molecules, modulating glucose
      homeostasis through activation of cell surface and nuclear receptors. Bile acid
      metabolism is altered in type 2 diabetes mellitus; however, whether this is of
      pathogenic consequence is not fully established. In this study urinary bile acid
      excretion in individuals with type 2 diabetes and matched healthy volunteers was
      assessed. Urinary bile acid excretion in type 2 diabetes patients was considered
      in the context of prevailing glycaemia and the patient body mass index. Urine
      bile acids were measured by liquid chromatography-tandem mass spectrometry,
      allowing individual quantification of 15 bile acid species. Urinary bile acid
      excretion in patients with type 2 diabetes who were normal weight (BMI 18.5-24.9
      kg/m2) and overweight (BMI 25-29.9 kg/m2) were elevated compared to healthy
      normal weight volunteers, both p<0.0001. In obese (BMI >= 30 kg/m2) type 2
      diabetes patients, urinary bile acid excretion was significantly lower than in
      the normal and overweight type 2 diabetes groups (both p<0.01). Total bile acid
      excretion positively correlated with HbA1c in normal (rs=0.85, p=<0.001) and
      overweight (rs=0.61, p=0.02) but not obese type 2 diabetes patients (rs=-0.08,
      p=0.73). The glycaemia-associated increases in urine bile acid excretion in
      normal weight and overweight type 2 diabetes seen in this study may represent
      compensatory increases in bile acid signalling to maintain glucose homeostasis.
      As such alterations appear blunted by obesity; further investigation of weight
      dependent effects of bile acid signalling on type 2 diabetes pathogenesis is
      warranted.

PMID- 24736332
TI  - Society of Critical Care Medicine Presidential Address-43rd Annual Congress,
      January 2014, San Francisco, California.

PMID- 24736331
TI  - The root canal system: a channel through which we can seed cells into grafts.
AB  - Bone tissue engineering is bringing hope to patients with jawbone defects, but
      this technology works well only for small- to moderate-sized jawbone defects. For
      large segmental jawbone defects, it is difficult to form the functional vascular
      networks within the graft due to limited diffusion of nutrition and uneven
      distribution of seed cells. From the standpoint of bionics, seed cells should be
      continuously transmitted into the graft to replace the necrotic cells during the
      entire process of bones regeneration. However, the existing one-time inoculation
      method (OIM) fails to achieve this goal because it is almost impossible to re
      open the wound and inoculate cells into grafts that have already been implanted
      into the body. Inspired by the anatomical structure of jawbones, we hypothesize
      that the root canal in teeth of jawbones could be used as a channel through which
      seed cells could be delivered into the graft. Therefore, the multiple-times
      inoculation method (MIM) could be achieved via the root canal system if defects
      are located on the maxillofacial bones with teeth. Both osteogenesis and
      vascularization would be promoted to a large extent because the engineered
      construct has a limitless supply of seed cells and growth factors.

PMID- 24736333
TI  - The highs and lows of blood pressure: toward meaningful clinical targets in
      patients with shock.
AB  - OBJECTIVE: Measurement of blood pressure is fundamental for the management of
      patients in shock, yet the physiological basis and meaning of blood pressure
      measurements are complex and often not well understood. This article is in two
      parts: part 1 deals with the mechanical and physiological aspects of blood
      pressure and its measurement and part 2 deals with the role of changes in
      regional resistances in the determination of tissue perfusion and bedside
      approaches to management of shock. DATA SOURCE AND SELECTION: This review is
      based on physiological principles from texts and experimental studies which
      elucidate some of the key principles. The views expressed are the author's
      synthesis of the views of others and his own opinions. DATA SYNTHESIS: Arterial
      blood pressure is a major determinant of regional flow and is often used as a
      surrogate indicator of tissue perfusion, but in reality, it is a poor indicator
      of blood flow. Blood pressure is determined by cardiac output (total flow) and
      total vascular resistance. Distribution of flow for a given blood pressure is
      dependent on the relative values of resistances in different vascular beds. If
      this distribution of resistances were known, this would be the ideal guide to
      therapy. Unfortunately, regional resistances cannot be assessed in the clinical
      setting, and so we are left with blood pressure as a guide to therapy.
      CONCLUSIONS: This article discusses the implications of these points and explores
      factors that need to be taken into account when designing empiric trials to
      determine appropriate blood pressure targets for patients in shock. Even if well
      studied empirically developed guidelines become available, it likely still will
      be important to individualize patient management and approaches for this are
      discussed too.

PMID- 24736334
TI  - Everybody, every day: an "awakening and breathing coordination, delirium
      monitoring/management, and early exercise/mobility" culture is feasible in your
      ICU.

PMID- 24736335
TI  - Systemic infections may cause cognitive deterioration and neurodegeneration.

PMID- 24736336
TI  - Severity of illness in pregnancy.

PMID- 24736337
TI  - ICU discharge bias reveals ethically troubling pay-for-performance benchmark
      metrics.

PMID- 24736338
TI  - A predisposition for sepsis after cardiac surgery-but what to do?

PMID- 24736339
TI  - Old soldiers never die, they just ... are transferred.

PMID- 24736340
TI  - The deadly impact of extreme drug resistance in Acinetobacter baumannii.

PMID- 24736341
TI  - ICU workforce: revisiting nurse staffing.

PMID- 24736342
TI  - More consistent site institutional review board (IRB) input-more consistent site
      IRB output.

PMID- 24736343
TI  - In gender-based outcomes, sex hormones may be important but it is in the genes*.

PMID- 24736344
TI  - Decontaminate inside and out: two is better than one.

PMID- 24736345
TI  - Using dexmedetomidine as adjunctive therapy for patients with severe alcohol
      withdrawal syndrome: another piece of the puzzle.

PMID- 24736346
TI  - Differential diagnosis by metabolic profile: a dream or reality?

PMID- 24736347
TI  - The ghost of christmas future: predicting pneumonia after cardiac operations.

PMID- 24736348
TI  - Intracranial pressure in acute liver failure: to bolt or not to bolt-that is the
      question.

PMID- 24736349
TI  - Fishing for improved outcomes in the critically ill.

PMID- 24736350
TI  - Why the reluctance to meaningfully mobilize ventilated patients? "The answer my
      friend is blowin' in the wind".

PMID- 24736351
TI  - Polymyxin B hemoperfusion: matching the cure to the disease.

PMID- 24736352
TI  - A cost-effective analysis of postoperative goal-directed therapy for high-risk
      surgical patients: improved outcomes are not enough ... you have to "show me the
      money".

PMID- 24736353
TI  - Bispectral index for prognostication after cardiac arrest: the holy grail at
      last?

PMID- 24736354
TI  - Tattered and torn: the life of a RBC on the extracorporeal membrane oxygenation
      circuit.

PMID- 24736355
TI  - Glucose control in pediatric burn patients: refining the search for the "sweet
      spot".

PMID- 24736356
TI  - The landscape of thromboprophylaxis utilization in critically ill children:
      sparse and variable.

PMID- 24736357
TI  - Over easy: an updated recipe for acute respiratory distress syndrome.

PMID- 24736358
TI  - Effective post-ICU rehabilitation of critical illness survivors: what do we know?

PMID- 24736359
TI  - Training requirements for critical care medicine internal medicine-based
      programs: helpful, haphazard, or harmony?

PMID- 24736360
TI  - RBC dysfunction in critical illness: driven by complement?

PMID- 24736361
TI  - Implementation strategies for quality improvement interventions to prevent
      catheter-related bloodstream infections.

PMID- 24736362
TI  - The authors reply.

PMID- 24736363
TI  - Keystone, matching Michigan, and bacteremia zero.

PMID- 24736364
TI  - The authors reply.

PMID- 24736365
TI  - Timing of parenteral nutrition support.

PMID- 24736366
TI  - The authors reply.

PMID- 24736367
TI  - Major confounders may influence multivariate analysis in a single-center
      observational study.

PMID- 24736368
TI  - The authors reply.

PMID- 24736369
TI  - Gut microbiome of the Hadza hunter-gatherers.
AB  - Human gut microbiota directly influences health and provides an extra means of
      adaptive potential to different lifestyles. To explore variation in gut
      microbiota and to understand how these bacteria may have co-evolved with humans,
      here we investigate the phylogenetic diversity and metabolite production of the
      gut microbiota from a community of human hunter-gatherers, the Hadza of Tanzania.
      We show that the Hadza have higher levels of microbial richness and biodiversity
      than Italian urban controls. Further comparisons with two rural farming African
      groups illustrate other features unique to Hadza that can be linked to a foraging
      lifestyle. These include absence of Bifidobacterium and differences in microbial
      composition between the sexes that probably reflect sexual division of labour.
      Furthermore, enrichment in Prevotella, Treponema and unclassified Bacteroidetes,
      as well as a peculiar arrangement of Clostridiales taxa, may enhance the Hadza's
      ability to digest and extract valuable nutrition from fibrous plant foods. 

PMID- 24736370
TI  - Indoor residual spraying in combination with insecticide-treated nets compared to
      insecticide-treated nets alone for protection against malaria: a cluster
      randomised trial in Tanzania.
AB  - BACKGROUND: Insecticide-treated nets (ITNs) and indoor residual spraying (IRS) of
      houses provide effective malaria transmission control. There is conflicting
      evidence about whether it is more beneficial to provide both interventions in
      combination. A cluster randomised controlled trial was conducted to investigate
      whether the combination provides added protection compared to ITNs alone. METHODS
      AND FINDINGS: In northwest Tanzania, 50 clusters (village areas) were randomly
      allocated to ITNs only or ITNs and IRS. Dwellings in the ITN+IRS arm were sprayed
      with two rounds of bendiocarb in 2012. Plasmodium falciparum prevalence rate
      (PfPR) in children 0.5-14 y old (primary outcome) and anaemia in children <5 y
      old (secondary outcome) were compared between study arms using three cross
      sectional household surveys in 2012. Entomological inoculation rate (secondary
      outcome) was compared between study arms. IRS coverage was approximately 90%. ITN
      use ranged from 36% to 50%. In intention-to-treat analysis, mean PfPR was 13% in
      the ITN+IRS arm and 26% in the ITN only arm, odds ratio = 0.43 (95% CI 0.19-0.97,
      n = 13,146). The strongest effect was observed in the peak transmission season, 6
      mo after the first IRS. Subgroup analysis showed that ITN users were additionally
      protected if their houses were sprayed. Mean monthly entomological inoculation
      rate was non-significantly lower in the ITN+IRS arm than in the ITN only arm,
      rate ratio = 0.17 (95% CI 0.03-1.08). CONCLUSIONS: This is the first randomised
      trial to our knowledge that reports significant added protection from combining
      IRS and ITNs compared to ITNs alone. The effect is likely to be attributable to
      IRS providing added protection to ITN users as well as compensating for
      inadequate ITN use. Policy makers should consider deploying IRS in combination
      with ITNs to control transmission if local ITN strategies on their own are
      insufficiently effective. Given the uncertain generalisability of these findings,
      it would be prudent for malaria control programmes to evaluate the cost
      effectiveness of deploying the combination. TRIAL REGISTRATION:
      www.ClinicalTrials.gov NCT01697852 Please see later in the article for the
      Editors' Summary.

PMID- 24736371
TI  - Lysosomal function is involved in 17beta-estradiol-induced estrogen receptor
      alpha degradation and cell proliferation.
AB  - The homeostatic control of the cellular proteome steady-state is dependent either
      on the 26S proteasome activity or on the lysosome function. The sex hormone
      17beta-estradiol (E2) controls a plethora of biological functions by binding to
      the estrogen receptor alpha (ERalpha), which is both a nuclear ligand-activated
      transcription factor and also an extrinsic plasma membrane receptor. Regulation
      of E2-induced physiological functions (e.g., cell proliferation) requires the
      synergistic activation of both transcription of estrogen responsive element (ERE)
      containing genes and rapid extra-nuclear phosphorylation of many different
      signalling kinases (e.g., ERK/MAPK; PI3K/AKT). Although E2 controls ERalpha
      intracellular content and activity via the 26S proteasome-mediated degradation,
      biochemical and microscopy-based evidence suggests a possible cross-talk among
      lysosomes and ERalpha activities. Here, we studied the putative localization of
      endogenous ERalpha to lysosomes and the role played by lysosomal function in
      ERalpha signalling. By using confocal microscopy and biochemical assays, we
      report that ERalpha localizes to lysosomes and to endosomes in an E2-dependent
      manner. Moreover, the inhibition of lysosomal function obtained by chloroquine
      demonstrates that, in addition to 26S proteasome-mediated receptor elimination,
      lysosome-based degradation also contributes to the E2-dependent ERalpha
      breakdown. Remarkably, the lysosome function is further involved in those ERalpha
      activities required for E2-dependent cell proliferation while it is dispensable
      for ERalpha-mediated ERE-containing gene transcription. Our discoveries reveal a
      novel lysosome-dependent degradation pathway for ERalpha and show a novel
      biological mechanism by which E2 regulates ERalpha cellular content and, as a
      consequence, cellular functions. 

PMID- 24736372
TI  - Association testing of clustered rare causal variants in case-control studies.
AB  - Biological evidence suggests that multiple causal variants in a gene may cluster
      physically. Variants within the same protein functional domain or gene regulatory
      element would locate in close proximity on the DNA sequence. However, spatial
      information of variants is usually not used in current rare variant association
      analyses. We here propose a clustering method (abbreviated as "CLUSTER"), which
      is extended from the adaptive combination of P-values. Our method combines the
      association signals of variants that are more likely to be causal. Furthermore,
      the statistic incorporates the spatial information of variants. With extensive
      simulations, we show that our method outperforms several commonly-used methods in
      many scenarios. To demonstrate its use in real data analyses, we also apply this
      CLUSTER test to the Dallas Heart Study data. CLUSTER is among the best methods
      when the effects of causal variants are all in the same direction. As variants
      located in close proximity are more likely to have similar impact on disease
      risk, CLUSTER is recommended for association testing of clustered rare causal
      variants in case-control studies. 

PMID- 24736373
TI  - Does US health reform reduce hospital readmission rates?

PMID- 24736374
TI  - Value, market preferences and trade of Beche-de-mer from Pacific Island sea
      cucumbers.
AB  - Market preferences of natural resources contribute to shape their exploitation
      and production. Beche-de-mer, the product after gutting, cooking, salting and
      drying sea cucumbers, is exported worldwide to Asian dried seafood markets. A
      better understanding of the trade, value and market preferences of Pacific island
      beche-de-mer could identify critical postharvest processing techniques and
      management strategies for fisheries and aquaculture. Data were collected on
      export prices and trade of beche-de-mer from Kiribati, Fiji, Tonga and New
      Caledonia, and the selling prices, respective sizes and organoleptic properties
      of the products in stores in China. Export prices varied considerably within and
      among the four countries and low-value species were the most exported by volume.
      Most of the beche-de-mer from the four Pacific islands is exported to Hong Kong,
      where quality products are sold and others are distributed to mainland China.
      Prices of the beche-de-mer in Chinese stores varied up to ten-fold and were
      mostly influenced by species, body size and, to a lesser extent, physical damage
      to the products. Market prices across species (averaging US$15-385 kg-1) appear
      to have mostly increased six- to twelve-fold over the past decade. The data
      allude that fisheries for Holothuria scabra, H. lessoni, H. fuscogilva, H.
      whitmaei and Thelenota ananas should be most carefully managed because they were
      the highest-value species and under greatest demand. The relationships between
      size of beche-de-mer and sale price were species specific and highly varied. This
      study also highlights the need for better regulations and/or enforcement of
      minimum size limits in sea cucumber fisheries, which can help to maximise
      economic benefits of wild stocks. 

PMID- 24736375
TI  - Transcriptome analysis of the hippocampus in novel rat model of febrile seizures.
AB  - Febrile seizures (FS) are the most common type of convulsive events in infants
      and young children, but the precise underlying genetic mechanism remains to be
      explored. To investigate the underlying pathogenic factors in FS and subsequent
      epilepsy, alterations in gene expression between the two new strains of rats
      (hyperthermia-prone [HP] vs hyperthermia-resistant [HR]), were investigated by
      using the Whole Rat Genome Oligo Microarray. This process identified 1,140
      differentially expressed genes (DEGs; 602 upregulated and 538 downregulated),
      which were analyzed to determine significant Gene Ontology (GO) categories,
      signaling pathways and gene networks. Based on the GO analyses, the modified
      genes are closely related to various FS pathogenesis factors, including immune
      and inflammatory responses and ion transport. Certain DEGs identified have not
      been previously examined in relation to FS pathogenesis. Among these genes is
      dipeptidyl peptidase 4 (DPP4), a gene closely linked to interleukin 6 (IL-6),
      which played a key role in the gene network analysis. Furthermore, sitagliptin, a
      DPP4 inhibitor significantly decreased epileptic discharge in rats, observed via
      electroencephalogram, suggesting an important role for DPP4 in FS. The
      effectiveness of sitagliptin in reducing seizure activity may occur through a
      mechanism that stabilizes cellular Ca2+ homeostasis. In addition, DPP4 expression
      may be regulated by DNA methylation. The hippocampal gene expression profiles in
      novel rat models of FS provides a large database of candidate genes and pathways,
      which will be useful for researchers interested in disorders of neuronal
      excitability.

PMID- 24736376
TI  - Analysis of vaginal microbicide film hydration kinetics by quantitative imaging
      refractometry.
AB  - We have developed a quantitative imaging refractometry technique, based on
      holographic phase microscopy, as a tool for investigating microscopic structural
      changes in water-soluble polymeric materials. Here we apply the approach to
      analyze the structural degradation of vaginal topical microbicide films due to
      water uptake. We implemented transmission imaging of 1-mm diameter film samples
      loaded into a flow chamber with a 1.5*2 mm field of view. After water was flooded
      into the chamber, interference images were captured and analyzed to obtain high
      resolution maps of the local refractive index and subsequently the volume
      fraction and mass density of film material at each spatial location. Here, we
      compare the hydration dynamics of a panel of films with varying thicknesses and
      polymer compositions, demonstrating that quantitative imaging refractometry can
      be an effective tool for evaluating and characterizing the performance of
      candidate microbicide film designs for anti-HIV drug delivery. 

PMID- 24736378
TI  - Education and WHO recommendations for fruit and vegetable intake are associated
      with better cognitive function in a disadvantaged Brazilian elderly population: a
      population-based cross-sectional study.
AB  - Brazil has one of the fastest aging populations in the world and the incidence of
      cognitive impairment in the elderly is expected to increase exponentially. We
      examined the association between cognitive impairment and fruit and vegetable
      intake and associated factors in a low-income elderly population. A cross
      sectional population-based study was carried out with 1849 individuals aged 65 or
      over living in Sao Paulo, Brazil. Cognitive function was assessed using the
      Community Screening Instrument for Dementia (CSI-D). Fruit and vegetable intake
      was assessed with a Food Frequency Questionnaire (FFQ) and categorized into
      quartiles of intake and into total daily fruit and vegetable intake using the cut
      off points for the WHO recommendations (<400 grams/day or >= 400 grams/day). The
      association between cognitive impairment and each quartile of intake, and WHO
      recommendation levels, was evaluated in two separate multivariate logistic
      models. The WHO recommendations for daily intakes >= 400 grams/day were
      significantly associated with 47% decreased prevalence of cognitive impairment.
      An effect modification was found in both models between cognitive impairment and
      "years of education and physical activity" and "years of education and blood
      levels of HDL" So that, having 1 or more years of education and being physically
      active or having 1 or more years of education and levels higher than 50 mg/dl of
      HDL-cholesterol strongly decreased the prevalence of cognitive impairment. In
      this socially deprived population with very low levels of education and physical
      activity and fruit and vegetable intake, those who attained WHO recommendations,
      had 1 year or more of education and were physically active had a significantly
      lower prevalence of cognitive impairment. A more comprehensive understanding of
      the social determinants of mental health is needed to develop effective public
      policies in developing countries.

PMID- 24736377
TI  - The 'ventral organs' of Pycnogonida (Arthropoda) are neurogenic niches of late
      embryonic and post-embryonic nervous system development.
AB  - Early neurogenesis in arthropods has been in the focus of numerous studies, its
      cellular basis, spatio-temporal dynamics and underlying genetic network being by
      now comparably well characterized for representatives of chelicerates, myriapods,
      hexapods and crustaceans. By contrast, neurogenesis during late embryonic and/or
      post-embryonic development has received less attention, especially in myriapods
      and chelicerates. Here, we apply (i) immunolabeling, (ii) histology and (iii)
      scanning electron microscopy to study post-embryonic ventral nerve cord
      development in Pseudopallene sp., a representative of the sea spiders
      (Pycnogonida), the presumable sister group of the remaining chelicerates. During
      early post-embryonic development, large neural stem cells give rise to additional
      ganglion cell material in segmentally paired invaginations in the ventral
      ectoderm. These ectodermal cell regions - traditionally designated as 'ventral
      organs' - detach from the surface into the interior and persist as apical cell
      clusters on the ventral ganglion side. Each cluster is a post-embryonic
      neurogenic niche that features a tiny central cavity and initially still houses
      larger neural stem cells. The cluster stays connected to the underlying
      ganglionic somata cortex via an anterior and a posterior cell stream. Cell
      proliferation remains restricted to the cluster and streams, and migration of
      newly produced cells along the streams seems to account for increasing ganglion
      cell numbers in the cortex. The pycnogonid cluster-stream-systems show striking
      similarities to the life-long neurogenic system of decapod crustaceans, and due
      to their close vicinity to glomerulus-like neuropils, we consider their possible
      involvement in post-embryonic (perhaps even adult) replenishment of olfactory
      neurons - as in decapods. An instance of a potentially similar post
      embryonic/adult neurogenic system in the arthropod outgroup Onychophora is
      discussed. Additionally, we document two transient posterior ganglia in the
      ventral nerve cord of Pseudopallene sp. and evaluate this finding in light of the
      often discussed reduction of a segmented 'opisthosoma' during pycnogonid
      evolution.

PMID- 24736379
TI  - Lessons learned and barriers discussed by beacon communities as they aim to
      improve health outcomes through health information technology: an interview by
      the informatics and technology expert panel.

PMID- 24736381
TI  - Prenylation modulates the bioavailability and bioaccumulation of dietary
      flavonoids.
AB  - Prenylflavonoids are distributed widely in the plant kingdom and have attracted
      appreciable attention because of their potential benefits for human health.
      Prenylation may be a promising tool for applying the biological functions of
      flavonoids to clinical uses. The bioavailability and bioaccumulation of
      prenylflavonoids have not been clarified, but extensive studies have been
      accomplished on their biological functions. This review provides current
      knowledge on the bioavailability of prenylflavonoids, including their absorption
      and metabolism in the intestine, as well as their bioaccumulation in specific
      tissues. Despite higher uptake into epithelial cells of the digestive tract, the
      bioavailability of single-dose prenylflavonoids seems to be lower than that of
      the parent flavonoids. Efflux from epithelial cells to the blood circulation is
      likely to be restricted by prenyl groups, resulting in insufficient increase in
      the plasma concentration. Rodent studies have revealed that prenylation enhances
      accumulation of naringenin in muscle tissue after long-term feeding; and that
      prenylation accelerates accumulation of quercetin in liver tissue. Efflux from
      hepatocytes to blood and enterohepatic circulations may be restricted by prenyl
      groups, thereby promoting slow excretion of prenylflavonoids from the blood
      circulation and efficient uptake to tissues. The hepatotoxicity and other
      deleterious effects, taken together with beneficial effects, should be considered
      because unexpectedly high accumulation may occur in some tissues after long-term
      supplementation. 

PMID- 24736383
TI  - A launch into OVS access and communication: journal of the future?

PMID- 24736382
TI  - Altered interactions between cardiac myosin binding protein-C and alpha-cardiac
      actin variants associated with cardiomyopathies.
AB  - The two genes most commonly associated with mutations linked to hypertrophic or
      dilated cardiomyopathies are beta-myosin and cardiac myosin binding protein-C
      (cMyBP-C). Both of these proteins interact with cardiac actin (ACTC). Currently
      there are 16 ACTC variants that have been found in patients with HCM or DCM.
      While some of these ACTC variants exhibit protein instability or polymerization
      deficiencies that might contribute to the development of disease, other changes
      could cause changes in protein-protein interactions between sarcomere proteins
      and ACTC. To test the hypothesis that changes in ACTC disrupt interactions with
      cMyBP-C, we examined the interactions between seven ACTC variants and the N
      terminal C0C2 fragment of cMyBP-C. We found there was a significant decrease in
      binding affinity (increase in Kd values) for the A331P and Y166C variants of
      ACTC. These results suggest that a change in the ability of cMyBP-C to bind actin
      filaments containing these ACTC protein variants might contribute to the
      development of disease. These results also provide clues regarding the binding
      site of the C0C2 fragment of cMyBP-C on F-actin.

PMID- 24736388
TI  - Targeted prevention of common mental health disorders in university students:
      randomised controlled trial of a transdiagnostic trait-focused web-based
      intervention.
AB  - BACKGROUND: A large proportion of university students show symptoms of common
      mental disorders, such as depression, anxiety, substance use disorders and eating
      disorders. Novel interventions are required that target underlying factors of
      multiple disorders. AIMS: To evaluate the efficacy of a transdiagnostic trait
      focused web-based intervention aimed at reducing symptoms of common mental
      disorders in university students. METHOD: Students were recruited online (n=1047,
      age: M=21.8, SD=4.2) and categorised into being at high or low risk for mental
      disorders based on their personality traits. Participants were allocated to a
      cognitive-behavioural trait-focused (n=519) or a control intervention (n=528)
      using computerised simple randomisation. Both interventions were fully automated
      and delivered online (trial registration: ISRCTN14342225). Participants were
      blinded and outcomes were self-assessed at baseline, at 6 weeks and at 12 weeks
      after registration. Primary outcomes were current depression and anxiety,
      assessed on the Patient Health Questionnaire (PHQ9) and Generalised Anxiety
      Disorder Scale (GAD7). Secondary outcome measures focused on alcohol use,
      disordered eating, and other outcomes. RESULTS: Students at high risk were
      successfully identified using personality indicators and reported poorer mental
      health. A total of 520 students completed the 6-week follow-up and 401 students
      completed the 12-week follow-up. Attrition was high across intervention groups,
      but comparable to other web-based interventions. Mixed effects analyses revealed
      that at 12-week follow up the trait-focused intervention reduced depression
      scores by 3.58 (p<.001, 95%CI [5.19, 1.98]) and anxiety scores by 2.87 (p=.018,
      95%CI [1.31, 4.43]) in students at high risk. In high-risk students, between
      group effect sizes were 0.58 (depression) and 0.42 (anxiety). In addition, self
      esteem was improved. No changes were observed regarding the use of alcohol or
      disordered eating. CONCLUSIONS: This study suggests that a transdiagnostic web
      based intervention for university students targeting underlying personality risk
      factors may be a promising way of preventing common mental disorders with a low
      intensity intervention. TRIAL REGISTRATION: ControlledTrials.com ISRCTN14342225.

PMID- 24736389
TI  - Do interventions designed to support shared decision-making reduce health
      inequalities? A systematic review and meta-analysis.
AB  - BACKGROUND: Increasing patient engagement in healthcare has become a health
      policy priority. However, there has been concern that promoting supported shared
      decision-making could increase health inequalities. OBJECTIVE: To evaluate the
      impact of SDM interventions on disadvantaged groups and health inequalities.
      DESIGN: Systematic review and meta-analysis of randomised controlled trials and
      observational studies. DATA SOURCES: CINAHL, the Cochrane Register of Controlled
      Trials, the Cochrane Database of Systematic Reviews, EMBASE, HMIC, MEDLINE, the
      NHS Economic Evaluation Database, Open SIGLE, PsycINFO and Web of Knowledge were
      searched from inception until June 2012. STUDY ELIGIBILITY CRITERIA: We included
      all studies, without language restriction, that met the following two criteria:
      (1) assess the effect of shared decision-making interventions on disadvantaged
      groups and/or health inequalities, (2) include at least 50% of people from
      disadvantaged groups, except if a separate analysis was conducted for this group.
      RESULTS: We included 19 studies and pooled 10 in a meta-analysis. The meta
      analyses showed a moderate positive effect of shared decision-making
      interventions on disadvantaged patients. The narrative synthesis suggested that,
      overall, SDM interventions increased knowledge, informed choice, participation in
      decision-making, decision self-efficacy, preference for collaborative decision
      making and reduced decisional conflict among disadvantaged patients. Further, 7
      out of 19 studies compared the intervention's effect between high and low
      literacy groups. Overall, SDM interventions seemed to benefit disadvantaged
      groups (e.g. lower literacy) more than those with higher literacy, education and
      socioeconomic status. Interventions that were tailored to disadvantaged groups'
      needs appeared most effective. CONCLUSION: Results indicate that shared decision
      making interventions significantly improve outcomes for disadvantaged patients.
      According to the narrative synthesis, SDM interventions may be more beneficial to
      disadvantaged groups than higher literacy/socioeconomic status patients. However,
      given the small sample sizes and variety in the intervention types, study design
      and quality, those findings should be interpreted with caution.

PMID- 24736390
TI  - Combined effects of defoliation and water stress on pine growth and non
      structural carbohydrates.
AB  - Climate change is expected to increase both pest insect damage and the occurrence
      of severe drought. There is therefore a need to better understand the combined
      effects of biotic and abiotic damage on tree growth in order to predict the multi
      factorial effect of climate change on forest ecosystem productivity. Indeed, the
      effect of stress interactions on tree growth is an increasingly important topic
      that greatly lacks experiments and data, and it is unlikely that the impact of
      combined stresses can be extrapolated from the outcomes of studies that focused
      on a single stress. We developed an original manipulative study under real field
      conditions where we applied artificial defoliation and induced water stress on 10
      year-old (~10 m high) maritime pine trees (Pinus pinaster Ait.). Tree response to
      combined stresses was quantitatively assessed following tree secondary growth and
      carbohydrate pools. Such a design allowed us to address the crucial question of
      combined stresses on trees under stand conditions, sharing soil supplies with
      neighboring trees. Our initial hypotheses were that (i) moderate defoliation can
      limit the impact of water stress on tree growth through reduced transpiration
      demand by a tree canopy partly defoliated and that (ii) defoliation results in
      reduced non-structural carbohydrate (NSC) pools, affecting tree tolerance to
      drought. Our results showed additive effects of defoliation and water stress on
      tree growth and contradict our initial hypothesis. Indeed, under stand
      conditions, we found that partial defoliation does not limit the impact of water
      stress through reduced transpiration. Our study also highlighted that, even if
      NSC in all organs were affected by defoliation, tree response to water stress was
      not triggered. We found that stem NSC were maintained or increased during the
      entire growing season, supporting literature-based hypotheses such as an active
      maintenance of the hydraulic system or another limiting resource for tree growth
      under defoliation. We also observed a significant decrease in root carbohydrates,
      which suggests a shift in the root carbon balance under defoliation. The decrease
      in carbohydrate supply under defoliation may not counterbalance the carbon use
      for mineral and water uptakes or a translocation to other tissues. 

PMID- 24736391
TI  - One-dimensional self-confinement promotes polymorph selection in large-area
      organic semiconductor thin films.
AB  - A crystal's structure has significant impact on its resulting biological,
      physical, optical and electronic properties. In organic electronics, 6,13(bis
      triisopropylsilylethynyl)pentacene (TIPS-pentacene), a small-molecule organic
      semiconductor, adopts metastable polymorphs possessing significantly faster
      charge transport than the equilibrium crystal when deposited using the solution
      shearing method. Here, we use a combination of high-speed polarized optical
      microscopy, in situ microbeam grazing incidence wide-angle X-ray-scattering and
      molecular simulations to understand the mechanism behind formation of metastable
      TIPS-pentacene polymorphs. We observe that thin-film crystallization occurs first
      at the air-solution interface, and nanoscale vertical spatial confinement of the
      solution results in formation of metastable polymorphs, a one-dimensional and
      large-area analogy to crystallization of polymorphs in nanoporous matrices. We
      demonstrate that metastable polymorphism can be tuned with unprecedented control
      and produced over large areas by either varying physical confinement conditions
      or by tuning energetic conditions during crystallization through use of solvent
      molecules of various sizes. 

PMID- 24736392
TI  - Feasibility and accuracy of nasal alar pulse oximetry.
AB  - BACKGROUND: The nasal ala is an attractive site for pulse oximetry because of
      perfusion by branches of the external and internal carotid arteries. We evaluated
      the accuracy of a novel pulse oximetry sensor custom designed for the nasal ala.
      METHODS: After IRB approval, healthy non-smoking subjects [n=12; aged 28 (23-41)
      yr; 6M/6F] breathed hypoxic mixtures of fresh gas by a facemask to achieve
      oxyhaemoglobin saturations of 70-100% measured by traditional co-oximetry from
      radial artery samples. Concurrent alar and finger pulse oximetry values were
      measured using probes designed for these sites. Data were analysed using the
      Bland-Altman method for multiple observations per subject. RESULTS: Bias,
      precision, and accuracy root mean square error (ARMS) over a range of 70-100%
      were significantly better for the alar probe compared with a standard finger
      probe. The mean bias for the alar and finger probes was 0.73% and 1.90%
      (P<0.001), respectively, with corresponding precision values of 1.65 and 1.83
      (P=0.015) and ARMS values of 1.78% and 2.72% (P=0.047). The coefficients of
      determination were 0.96 and 0.96 for the alar and finger probes, respectively.
      The within/between-subject variation for the alar and finger probes were
      1.14/1.57% and 1.87/1.47%, respectively. The limits of agreement were 3.96/-2.50%
      and 5.48/-1.68% for the alar and finger probes, respectively. CONCLUSIONS: Nasal
      alar pulse oximetry is feasible and demonstrates accurate pulse oximetry values
      over a range of 70-100%. The alar probe demonstrated greater accuracy compared
      with a conventional finger pulse oximeter.

PMID- 24736393
TI  - Isotonic crystalloid solutions: a structured review of the literature.
AB  - BACKGROUND: Several different crystalloid solutions are available for i.v. fluid
      administration but there is little information about their specific advantages
      and disadvantages. METHODS: We performed a systematic search of MEDLINE, EMBASE,
      and CENTRAL up until May 17, 2012, selecting all prospective human studies that
      directly compared any near-isotonic crystalloids and reported any outcome.
      RESULTS: From the 5060 articles retrieved in the search, only 28 met the
      selection criteria. There was considerable heterogeneity among the studies.
      Several articles reported an increased incidence of hyperchloraemic acidosis with
      the use of normal saline, and others an increase in blood lactate levels when
      large amounts of Ringer's lactate solutions were infused. From the limited data
      available, normal saline administration appears to be associated with increased
      blood loss and greater red blood cell transfusion volumes in high-risk
      populations compared to Ringer's lactate. Possible effects of the different
      solutions on renal function, inflammatory response, temperature, hepatic
      function, glucose metabolism, and splanchnic perfusion are also reported. The
      haemodynamic profiles of all the solutions were similar. CONCLUSIONS: Different
      solutions have different effects on acid-base status, electrolyte levels,
      coagulation, renal, and hepatic function. Whether these differences have clinical
      consequences remains unclear.

PMID- 24736394
TI  - KCTD1 suppresses canonical Wnt signaling pathway by enhancing beta-catenin
      degradation.
AB  - The canonical Wnt signaling pathway controls normal embryonic development,
      cellular proliferation and growth, and its aberrant activity results in human
      carcinogenesis. The core component in regulation of this pathway is beta-catenin,
      but molecular regulation mechanisms of beta-catenin stability are not completely
      known. Here, our recent studies have shown that KCTD1 strongly inhibits TCF/LEF
      reporter activity. Moreover, KCTD1 interacted with beta-catenin both in vivo by
      co-immunoprecipitation as well as in vitro through GST pull-down assays. We
      further mapped the interaction regions to the 1-9 armadillo repeats of beta
      catenin and the BTB domain of KCTD1, especially Position Ala-30 and His-33.
      Immunofluorescence analysis indicated that KCTD1 promotes the cytoplasmic
      accumulation of beta-catenin. Furthermore, protein stability assays revealed that
      KCTD1 enhances the ubiquitination/degradation of beta-catenin in a concentration
      dependent manner in HeLa cells. And the degradation of beta-catenin mediated by
      KCTD1 was alleviated by the proteasome inhibitor, MG132. In addition, KCTD1
      mediated beta-catenin degradation was dependent on casein kinase 1 (CK1)- and
      glycogen synthase kinase-3beta (GSK-3beta)-mediated phosphorylation and enhanced
      by the E3 ubiquitin ligase beta-transducin repeat-containing protein (beta-TrCP).
      Moreover, KCTD1 suppressed the expression of endogenous Wnt downstream genes and
      transcription factor AP-2alpha. Finally, we found that Wnt pathway member APC and
      tumor suppressor p53 influence KCTD1-mediated downregulation of beta-catenin.
      These results suggest that KCTD1 functions as a novel inhibitor of Wnt signaling
      pathway. 

PMID- 24736396
TI  - PSA screening for prostate cancer.

PMID- 24736395
TI  - The pathology of severe dengue in multiple organs of human fatal cases:
      histopathology, ultrastructure and virus replication.
AB  - Dengue is a public health problem, with several gaps in understanding its
      pathogenesis. Studies based on human fatal cases are extremely important and may
      clarify some of these gaps. In this work, we analyzed lesions in different organs
      of four dengue fatal cases, occurred in Brazil. Tissues were prepared for
      visualization in optical and electron microscopy, with damages quantification. As
      expected, we observed in all studied organ lesions characteristic of severe
      dengue, such as hemorrhage and edema, although other injuries were also detected.
      Cases presented necrotic areas in the liver and diffuse macro and microsteatosis,
      which were more accentuated in case 1, who also had obesity. The lung was the
      most affected organ, with hyaline membrane formation associated with mononuclear
      infiltrates in patients with pre-existing diseases such as diabetes and obesity
      (cases 1 and 2, respectively). These cases had also extensive acute tubular
      necrosis in the kidney. Infection induced destruction of cardiac fibers in most
      cases, with absence of nucleus and loss of striations, suggesting myocarditis.
      Spleens revealed significant destruction of the germinal centers and atrophy of
      lymphoid follicles, which may be associated to decrease of T cell number.
      Circulatory disturbs were reinforced by the presence of megakaryocytes in
      alveolar spaces, thrombus formation in glomerular capillaries and loss of
      endothelium in several tissues. Besides histopathological and ultrastructural
      observations, virus replication were investigated by detection of dengue
      antigens, especially the non-structural 3 protein (NS3), and confirmed by the
      presence of virus RNA negative strand (in situ hybridization), with second
      staining for identification of some cells. Results showed that dengue had broader
      tropism comparing to what was described before in literature, replicating in
      hepatocytes, type II pneumocytes and cardiac fibers, as well as in resident and
      circulating monocytes/macrophages and endothelial cells. 

PMID- 24736398
TI  - Intracranial hypertension and outcome following severe traumatic brain injury.

PMID- 24736397
TI  - Chlamydial induction of hydrosalpinx in 11 strains of mice reveals multiple host
      mechanisms for preventing upper genital tract pathology.
AB  - The female lower genital tract is constantly exposed to microbial infection, some
      of which can ascend to and cause pathology such as hydrosalpinx in the upper
      genital tract, which can affect fertility. To understand host mechanisms for
      preventing upper genital tract pathology, we screened 11 inbred strains of mice
      for hydrosalpinx induction by C. muridarum. When examined on days 60 to 80 after
      intravaginal infection, the 11 strains fell into 3 groups based on their
      hydrosalpinx severity: CBA/J and SJL/J mice were highly susceptible with a
      hydrosalpinx score of 5 or greater; Balb/c, C57BL/6J, C57BL/10J, C3H/HeJ and
      C3H/HeN were susceptible with a score between 1 and <5; NOD/ShiLtJ, DBA/1J,
      DBA/2J and A/J were resistant with a score of <1. The diverse range of mouse
      susceptibility to hydrosalpinx induction may reflect the varied clinical outcomes
      of C. trachomatis-infected women. When the 11 strains were infected via an
      intrauterine inoculation to bypass the requirement for ascension, higher
      incidence and more severe hydrosalpinges were induced in most mice, indicating
      that the interaction between chlamydial ascension and host control of ascension
      is critical for determining susceptibility to hydrosalpinx development in many
      mice. However, a few mouse strains resisted significant exacerbation of
      hydrosalpinx by intrauterine infection, indicating that these mice have evolved
      ascension-independent mechanisms for preventing upper genital tract pathology.
      Together, the above observations have demonstrated that different strains of mice
      can prevent upper genital tract pathology by using different mechanisms. 

PMID- 24736399
TI  - Development and characterization of polymorphic EST-SSR and genomic SSR markers
      for Tibetan annual wild barley.
AB  - Tibetan annual wild barley is rich in genetic variation. This study was aimed at
      the exploitation of new SSRs for the genetic diversity and phylogenetic analysis
      of wild barley by data mining. We developed 49 novel EST-SSRs and confirmed 20
      genomic SSRs for 80 Tibetan annual wild barley and 16 cultivated barley
      accessions. A total of 213 alleles were generated from 69 loci with an average of
      3.14 alleles per locus. The trimeric repeats were the most abundant motifs
      (40.82%) among the EST-SSRs, while the majority of the genomic SSRs were di
      nuleotide repeats. The polymorphic information content (PIC) ranged from 0.08 to
      0.75 with a mean of 0.46. Besides this, the expected heterozygosity (He) ranged
      from 0.0854 to 0.7842 with an average of 0.5279. Overall, the polymorphism of
      genomic SSRs was higher than that of EST-SSRs. Furthermore, the number of alleles
      and the PIC of wild barley were both higher than that of cultivated barley, being
      3.12 vs 2.59 and 0.44 vs 0.37. Indicating more polymorphism existed in the
      Tibetan wild barley than in cultivated barley. The 96 accessions were divided
      into eight subpopulations based on 69 SSR markers, and the cultivated genotypes
      can be clearly separated from wild barleys. A total of 47 SSR-containing EST
      unigenes showed significant similarities to the known genes. These EST-SSR
      markers have potential for application in germplasm appraisal, genetic diversity
      and population structure analysis, facilitating marker-assisted breeding and crop
      improvement in barley. 

PMID- 24736400
TI  - Developing an item bank to measure economic quality of life for individuals with
      disabilities.
AB  - OBJECTIVE: To develop and evaluate the psychometric properties of an item set
      measuring economic quality of life (QOL) for use by individuals with
      disabilities. DESIGN: Survey. SETTING: Community settings. PARTICIPANTS:
      Individuals with disabilities completed individual interviews (n=64),
      participated in focus groups (n=172), and completed cognitive interviews (n=15).
      Inclusion criteria included the following: traumatic brain injury, spinal cord
      injury, or stroke; age >=18 years; and ability to read and speak English. We
      calibrated the items with 305 former rehabilitation inpatients. INTERVENTIONS:
      None. MAIN OUTCOME MEASURE: Economic QOL. RESULTS: Confirmatory factor analysis
      showed acceptable fit indices (comparative fit index=.939, root mean square error
      of approximation=.089) for the 37 items. However, 3 items demonstrated local item
      dependence. Dropping 9 items improved fit and obviated local dependence. Rasch
      analysis of the remaining 28 items yielded a person reliability of .92,
      suggesting that these items discriminate about 4 economic QOL levels.
      CONCLUSIONS: We developed a 28-item bank that measures economic aspects of QOL.
      Preliminary confirmatory factor analysis and Rasch analysis results support the
      psychometric properties of this new measure. It fills a gap in health-related QOL
      measurement by describing the economic barriers and facilitators of community
      participation. Future development will make the item bank available as a computer
      adaptive test.

PMID- 24736401
TI  - Signaling adaptor protein SH2B1 enhances neurite outgrowth and accelerates the
      maturation of human induced neurons.
AB  - Recent advances in somatic cell reprogramming have highlighted the plasticity of
      the somatic epigenome, particularly through demonstrations of direct lineage
      reprogramming of adult mouse and human fibroblasts to induced pluripotent stem
      cells (iPSCs) and induced neurons (iNs) under defined conditions. However, human
      cells appear to be less plastic and have a higher epigenetic hurdle for
      reprogramming to both iPSCs and iNs. Here, we show that SH2B adaptor protein
      1beta (SH2B1) can enhance neurite outgrowth of iNs reprogrammed from human
      fibroblasts as early as day 14, when combined with miR124 and transcription
      factors BRN2 and MYT1L (IBM) under defined conditions. These SH2B1-enhanced iNs
      (S-IBM) showed canonical neuronal morphology, and expressed multiple neuronal
      markers, such as TuJ1, NeuN, and synapsin, and functional proteins for
      neurotransmitter release, such as GABA, vGluT2, and tyrosine hydroxylase.
      Importantly, SH2B1 accelerated mature process of functional neurons and exhibited
      action potentials as early as day 14; without SH2B1, the IBM iNs do not exhibit
      action potentials until day 21. Our data demonstrate that SH2B1 can enhance
      neurite outgrowth and accelerate the maturation of human iNs under defined
      conditions. This approach will facilitate the application of iNs in regenerative
      medicine and in vitro disease modeling. 

PMID- 24736404
TI  - Thermalization of field driven quantum systems.
AB  - There is much interest in how quantum systems thermalize after a sudden change,
      because unitary evolution should preclude thermalization. The eigenstate
      thermalization hypothesis resolves this because all observables for quantum
      states in a small energy window have essentially the same value; it is violated
      for integrable systems due to the infinite number of conserved quantities. Here,
      we show that when a system is driven by a DC electric field there are five
      generic behaviors: (i) monotonic or (ii) oscillatory approach to an infinite
      temperature steady state; (iii) monotonic or (iv) oscillatory approach to a
      nonthermal steady state; or (v) evolution to an oscillatory state. Examining the
      Hubbard model (which thermalizes under a quench) and the Falicov-Kimball model
      (which does not), we find both exhibit scenarios (i-iv), while only Hubbard shows
      scenario (v). This shows richer behavior than in interaction quenches and
      integrability in the absence of a field plays no role. 

PMID- 24736403
TI  - Messenger RNA- versus retrovirus-based induced pluripotent stem cell
      reprogramming strategies: analysis of genomic integrity.
AB  - The use of synthetic messenger RNAs to generate human induced pluripotent stem
      cells (iPSCs) is particularly appealing for potential regenerative medicine
      applications, because it overcomes the common drawbacks of DNA-based or virus
      based reprogramming strategies, including transgene integration in particular. We
      compared the genomic integrity of mRNA-derived iPSCs with that of retrovirus
      derived iPSCs generated in strictly comparable conditions, by single-nucleotide
      polymorphism (SNP) and copy number variation (CNV) analyses. We showed that mRNA
      derived iPSCs do not differ significantly from the parental fibroblasts in SNP
      analysis, whereas retrovirus-derived iPSCs do. We found that the number of CNVs
      seemed independent of the reprogramming method, instead appearing to be clone
      dependent. Furthermore, differentiation studies indicated that mRNA-derived iPSCs
      differentiated efficiently into hepatoblasts and that these cells did not load
      additional CNVs during differentiation. The integration-free hepatoblasts that
      were generated constitute a new tool for the study of diseased hepatocytes
      derived from patients' iPSCs and their use in the context of stem cell-derived
      hepatocyte transplantation. Our findings also highlight the need to conduct
      careful studies on genome integrity for the selection of iPSC lines before using
      them for further applications. 

PMID- 24736402
TI  - Cobalt protoporphyrin pretreatment protects human embryonic stem cell-derived
      cardiomyocytes from hypoxia/reoxygenation injury in vitro and increases graft
      size and vascularization in vivo.
AB  - Human embryonic stem cell-derived cardiomyocytes (hESC-CMs) can regenerate
      infarcted myocardium. However, when implanted into acutely infarcted hearts, few
      cells survive the first week postimplant. To improve early graft survival, hESC
      CMs were pretreated with cobalt protoporphyrin (CoPP), a transcriptional
      activator of cytoprotective heme oxygenase-1 (HO-1). When hESC-CMs were
      challenged with an in vitro hypoxia/reoxygenation injury, mimicking cell
      transplantation into an ischemic site, survival was significantly greater among
      cells pretreated with CoPP versus phosphate-buffered saline (PBS)-pretreated
      controls. Compared with PBS-pretreated cells, CoPP-pretreated hESC-CM
      preparations exhibited higher levels of HO-1 expression, Akt phosphorylation, and
      vascular endothelial growth factor production, with reduced apoptosis, and a 30%
      decrease in intracellular reactive oxygen species. For in vivo translation, 1 *
      10(7) hESC-CMs were pretreated ex vivo with CoPP or PBS and then injected
      intramyocardially into rat hearts immediately following acute infarction
      (permanent coronary ligation). At 1 week, hESC-CM content, assessed by
      quantitative polymerase chain reaction for human Alu sequences, was 17-fold
      higher in hearts receiving CoPP- than PBS-pretreated cells. On histomorphometry,
      cardiomyocyte graft size was 2.6-fold larger in hearts receiving CoPP- than PBS
      pretreated cells, occupying up to 12% of the ventricular area. Vascular density
      of host-perfused human-derived capillaries was significantly greater in grafts
      composed of CoPP- than PBS-pretreated cells. Taken together, these experiments
      demonstrate that ex vivo pretreatment of hESC-CMs with a single dose of CoPP
      before intramyocardial implantation more than doubled resulting graft size and
      improved early graft vascularization in acutely infarcted hearts. These findings
      open the door for delivery of these, or other, stem cells during acute
      interventional therapy following myocardial infarction or ischemia. 

PMID- 24736405
TI  - Infection of apple by apple stem grooving virus leads to extensive alterations in
      gene expression patterns but no disease symptoms.
AB  - To understand the molecular basis of viral diseases, transcriptome profiling has
      been widely used to correlate host gene expression change patterns with disease
      symptoms during viral infection in many plant hosts. We used infection of apple
      by Apple stem grooving virus (ASGV), which produces no disease symptoms, to
      assess the significance of host gene expression changes in disease development.
      We specifically asked the question of whether such asymptomatic infection is
      attributed to limited changes in host gene expression. Using RNA-seq, we
      identified a total of 184 up-regulated and 136 down-regulated genes in apple
      shoot cultures permanently infected by ASGV in comparison with virus-free shoot
      cultures. As in most plant hosts showing disease symptoms during viral infection,
      these differentially expressed genes encode known or putative proteins involved
      in cell cycle, cell wall biogenesis, response to biotic and abiotic stress,
      development and fruit ripening, phytohormone function, metabolism, signal
      transduction, transcription regulation, translation, transport, and
      photosynthesis. Thus, global host gene expression changes do not necessarily lead
      to virus disease symptoms. Our data suggest that the general approaches to
      correlate host gene expression changes under viral infection conditions to
      specific disease symptom, based on the interpretation of transcription profiling
      data and altered individual gene functions, may have limitations depending on
      particular experimental systems.

PMID- 24736406
TI  - Mice rescued from severe malaria are protected against renal injury during a
      second kidney insult.
AB  - Malaria is a worldwide disease that leads to 1 million deaths per year.
      Plasmodium falciparum is the species responsible for the most severe form of
      malaria leading to different complications. Beyond the development of cerebral
      malaria, impairment of renal function is a mortality indicator in infected
      patients. Treatment with antimalarial drugs can increase survival, however the
      long-term effects of malaria on renal disease, even after treatment with
      antimalarials, are unknown. The aim of this study was to evaluate the effect of
      antimalarial drug treatment on renal function in a murine model of severe malaria
      and then evaluate kidney susceptibility to a second renal insult. Initially, mice
      infected with Plasmodium berghei ANKA achieved 20% parasitemia on day 5 post
      infection, which was completely abolished after treatment with 25 mg/kg
      artesunate and 40 mg/kg mefloquine. The treatment also decreased plasma
      creatinine levels by 43% and partially reversed the reduction in the glomerular
      filtration rate induced by infection. The urinary protein/creatinine ratio,
      collagen deposition, and size of the interstitial space decreased by 75%, 40%,
      and 20%, respectively, with drugs compared with untreated infected animals. In
      infected-treated mice that underwent a second renal insult, the plasma creatinine
      level decreased by 60% and the glomerular filtration rate increased compared with
      infected animals treated only with antimalarials. The number of glomerular cells,
      collagen deposition and the size of the interstitial space decreased by 20%,
      39.4%, and 41.3%, respectively, in the infected group that underwent a second
      renal insult compared with the infected-treated groups. These functional and
      structural data show that renal injury observed in a murine model of severe
      malaria is partially reversed after antimalarial drug treatment, making the
      kidney less susceptible to a second renal insult. 

PMID- 24736407
TI  - Investigation of key interventions for shigellosis outbreak control in China.
AB  - Shigellosis is a major public health concern in China, where waterborne disease
      outbreaks are common. Shigellosis-containing strategies, mostly single or
      multiple interventions, are implemented by primary-level health departments.
      Systematic assessment of the effectiveness of these measures is scarce. To
      estimate the efficacy of commonly used intervention strategies, we developed a
      Susceptible-Exposed-Infectious/Asymptomatic-Recovered-Water model. No
      intervention was predicted to result in a total attack rate (TAR) of 90% of the
      affected population (95% confidence interval [CI]: 86.65-92.80) and duration of
      outbreak (DO) of 89 days, and the use of single-intervention strategies can be
      futile or even counter-productive. Prophylactics and water disinfection did not
      improve TAR or DO. School closure for up to 3 weeks did not help but only
      increased DO. Isolation alone significantly increased DO. Only antibiotics
      treatment could shorten the DO to 35 days with TAR unaffected. We observed that
      these intervention effects were additive when in combined usage under most
      circumstances. Combined intervention "Isolation+antibiotics+prophylactics+water
      disinfection" was predicted to result in the lowest TAR (41.9%, 95%CI: 36.97
      47.04%) and shortest DO (28 days). Our actual Shigellosis control implementation
      that also included school closure for 1 week, attained comparable results and the
      modeling produced an epidemic curve of Shigellosis highly similar to our actual
      outbreak data. This lends a strong support to the reality of our model that
      provides a possible reference for public health professionals to evaluate their
      strategies towards Shigellosis control. 

PMID- 24736408
TI  - Relationship of circulating hyaluronic acid levels to disease control in asthma
      and asthmatic pregnancy.
AB  - Uncontrolled asthma is a risk factor for pregnancy-related complications.
      Hyaluronic acid (HA), a potential peripheral blood marker of tissue fibrosis in
      various diseases, promotes eosinophil survival and plays a role in asthmatic
      airway inflammation as well as in physiological processes necessary to maintain
      normal pregnancy; however the level of circulating HA in asthma and asthmatic
      pregnancy is unknown. We investigated HA levels in asthmatic patients (N = 52;
      asthmatic pregnant (AP) N = 16; asthmatic non-pregnant (ANP) N = 36) and tested
      their relationship to asthma control. Serum HA level was lower in AP than in ANP
      patients (27 [24.7-31.55] vs. 37.4 [30.1-66.55] ng/mL, p = 0.006); the difference
      attenuated to a trend after its adjustment for patients' age (p = 0.056). HA
      levels and airway resistance were positively (r = 0.467, p = 0.004), HA levels
      and Asthma Control Test (ACT) total score inversely (r = -0.437, p = 0.01)
      associated in ANP patients; these relationships remained significant even after
      their adjustments for age. The potential value of HA in the determination of
      asthma control was analyzed using ROC analysis which revealed that HA values
      discriminate patients with ACT total score >=20 (controlled patients) and <20
      (uncontrolled patients) with a 0.826 efficacy (AUC, 95% CI: 0.69-0.97, p = 0.001)
      when 37.4 ng/mL is used as cut-off value in ANP group, and with 0.78 efficacy
      (AUC, 95% CI: 0.65-0.92, p = 0.0009) in the whole asthmatic cohort. In conclusion
      circulating HA might be a marker of asthma control, as it correlates with airway
      resistance and has good sensitivity in the detection of impaired asthma control.
      Decrease of HA level in pregnancy may be the consequence of pregnancy induced
      immune tolerance. 

PMID- 24736409
TI  - A model for Sclerotinia sclerotiorum infection and disease development in
      lettuce, based on the effects of temperature, relative humidity and ascospore
      density.
AB  - The plant pathogen Sclerotinia sclerotiorum can cause serious losses on lettuce
      crops worldwide and as for most other susceptible crops, control relies on the
      application of fungicides, which target airborne ascospores. However, the
      efficacy of this approach depends on accurate timing of these sprays, which could
      be improved by an understanding of the environmental conditions that are
      conducive to infection. A mathematical model for S. sclerotiorum infection and
      disease development on lettuce is presented here for the first time, based on
      quantifying the effects of temperature, relative humidity (RH) and ascospore
      density in multiple controlled environment experiments. It was observed that
      disease can develop on lettuce plants inoculated with dry ascospores in the
      absence of apparent leaf wetness (required for spore germination). To explain
      this, the model conceptualises an infection court area containing microsites (in
      leaf axils and close to the stem base) where conditions are conducive to
      infection, the size of which is modified by ambient RH. The model indicated that
      minimum, maximum and optimum temperatures for ascospore germination were 0.0,
      29.9 and 21.7 degrees C respectively and that maximum rates of disease
      development occurred at spore densities >87 spores cm-2. Disease development was
      much more rapid at 80-100% RH at 20 degrees C, compared to 50-70% RH and resulted
      in a greater proportion of lettuce plants infected. Disease development was also
      more rapid at 15-27 degrees C compared to 5-10 degrees C (85% RH). The model was
      validated by a further series of independent controlled environment experiments
      where both RH and temperature were varied and generally simulated the pattern of
      disease development well. The implications of the results in terms of Sclerotinia
      disease forecasting are discussed. 

PMID- 24736410
TI  - Cathelicidin LL-37 induces time-resolved release of LTB4 and TXA2 by human
      macrophages and triggers eicosanoid generation in vivo.
AB  - In humans, LL-37 and eicosanoids are important mediators of inflammation and
      immune responses. Here we report that LL-37 promotes leukotriene B4 (LTB4) and
      thromboxane A2 (TXA2) generation by human monocyte-derived macrophages (HMDMs).
      LL-37 evokes calcium mobilization apparently via the P2X7 receptor (P2X7R),
      activation of ERK1/2 and p38 MAPKs, as well as cytosolic phospholipase A2 (cPLA2)
      and 5-lipoxygenase in HMDMs, leading to an early (1 h) release of LTB4.
      Similarly, TXA2 production at an early time involved the same signaling sequence
      along an LL-37-P2X7R-cPLA2-cyclooxygenase-1 (COX-1) axis. However, at later (6-8
      h) time points, internalized LL-37 up-regulates COX-2 expression, promoting TXA2
      production. Furthermore, intraperitoneal injection of mice with murine
      cathelicidin-related antimicrobial peptide (mCRAMP) induces significantly higher
      levels of LTB4 and TXA2 in mouse ascites rich in macrophages. Conversely,
      cathelicidin-deficient (Cnlp(-/-)) mice produce much less LTB4 and TXB2 in vivo
      in response to TNF-alpha compared with control mice. We conclude that LL-37
      elicits a biphasic release of eicosanoids in macrophages with early, Ca(2+)
      dependent formation of LTB4 and TXA2 followed by a late peak of TXA2, generated
      via induction of COX-2 by internalized LL-37, thus allowing eicosanoid production
      in a temporally controlled manner. Moreover, our findings provide evidence that
      LL-37 is an endogenous regulator of eicosanoid-dependent inflammatory responses
      in vivo.

PMID- 24736411
TI  - Contribution of galactoglycerolipids to the 3-dimensional architecture of
      thylakoids.
AB  - Thylakoid membranes, the universal structure where photosynthesis takes place in
      all oxygenic photosynthetic organisms from cyanobacteria to higher plants, have a
      unique lipid composition. They contain a high fraction of 2 uncharged
      glycolipids, the galactoglycerolipids mono- and digalactosyldiacylglycerol (MGDG
      and DGDG, respectively), and an anionic sulfolipid, sulfoquinovosediacylglycerol
      (SQDG). A remarkable feature of the evolution from cyanobacteria to higher plants
      is the conservation of MGDG, DGDG, SQDG, and phosphatidylglycerol (PG), the major
      phospholipid of thylakoids. Using neutron diffraction on reconstituted thylakoid
      lipid extracts, we observed that the thylakoid lipid mixture self-organizes as a
      regular stack of bilayers. This natural lipid mixture was shown to switch from
      hexagonal II toward lamellar phase on hydration. This transition and the observed
      phase coexistence are modulated by the fine-tuning of the lipid profile, in
      particular the MGDG/DGDG ratio, and by the hydration. Our analysis highlights the
      critical role of DGDG as a contributing component to the membrane stacking via
      hydrogen bonds between polar heads of adjacent bilayers. DGDG interactions
      balance the repulsive electrostatic contribution of the charged lipids PG and
      SQDG and allow the persistence of regularly stacked membranes at high hydration.
      In developmental contexts or in response to environmental variations, these
      properties can contribute to the highly dynamic flexibility of plastid structure.

PMID- 24736413
TI  - Evaluation of therapeutic effects of natural killer (NK) cell-based immunotherapy
      in mice using in vivo apoptosis bioimaging with a caspase-3 sensor.
AB  - Natural killer (NK) cell-based immunotherapy is a promising strategy for cancer
      treatment, and caspase-3 is an important effector molecule in NK cell-mediated
      apoptosis in cancers. Here, we evaluated the antitumor effects of NK cell-based
      immunotherapy by serial noninvasive imaging of apoptosis using a caspase-3 sensor
      in mice with human glioma xenografts. Human glioma cells expressing both a
      caspase-3 sensor as a surrogate marker for caspase-3 activation and Renilla
      luciferase (Rluc) as a surrogate marker for cell viability were established and
      referred to as D54-CR cells. Human NK92 cells were used as effector cells.
      Treatment with NK92 cells resulted in a time- and effector number-dependent
      increase in bioluminescence imaging (BLI) activity of the caspase-3 sensor in D54
      CR cells in vitro. Caspase-3 activation by NK92 treatment was blocked by Z-VAD
      treatment in D54-CR cells. Transfusion of NK92 cells induced an increase of the
      BLI signal by caspase-3 activation in a dose- and time-dependent manner in D54-CR
      tumor-bearing mice but not in PBS-treated mice. Accordingly, sequential BLI with
      the Rluc reporter gene revealed marked retardation of tumor growth in the NK92
      treatment group but not in the PBS-treatment group. These data suggest that
      noninvasive imaging of apoptosis with a caspase-3 sensor can be used as an
      effective tool for evaluation of therapeutic efficacy as well as for optimization
      of NK cell-based immunotherapy.-Lee, H. W., Singh, T. D., Lee, S.-W., Ha, J.-H.,
      Rehemtulla, A., Ahn, B.-C., Jeon, Y.-H., Lee, J. Evaluation of therapeutic
      effects of natural killer (NK) cell-based immunotherapy in mice using in vivo
      apoptosis bioimaging with a caspase-3 sensor. 

PMID- 24736412
TI  - Rim formation is not a prerequisite for distribution of cone photoreceptor outer
      segment proteins.
AB  - Retinal degeneration slow (RDS/PRPH2) is critical for the formation of the
      disc/lamella rim in photoreceptor outer segments (OSs), but plays a different
      role in rods vs. cones. Without RDS, rods fail to form OSs, however, cones
      lacking RDS (in the rds(-/-)/Nrl(-/-)) exhibit balloon-like OSs devoid of
      lamellae. We show that distribution of most proteins in the lamella and PM
      domains is preserved even in the absence of RDS, rim, and lamella structures.
      However, the rim protein prominin-1 exhibits altered trafficking and OS
      localization, suggesting that proper targeting and distribution of rim proteins
      may require RDS. Our ultrastructural studies show that in cones, OS formation is
      initiated by the growth of opsin-containing membrane with RDS-mediated rim
      formation as a secondary step. This is directly opposite to rods and
      significantly advances our understanding of the role of the rim in cone OS
      morphogenesis. Furthermore, our results suggest that the unique folded lamella
      architecture of the cone OS may maximize density or proximity of
      phototransduction proteins, but is not required for OS function or for protein
      distribution and retention in different membrane domains.

PMID- 24736414
TI  - Remembering David L. Epstein, MMM, MD, 1944-2014.

PMID- 24736415
TI  - Ginkgo biloba extract improves visual field damage in some patients affected by
      normal-tension glaucoma.

PMID- 24736416
TI  - Author response: Ginkgo biloba extract improves visual field damage in some
      patients affected by normal-tension glaucoma.

PMID- 24736417
TI  - Chronic hypertension during pregnancy.

PMID- 24736418
TI  - Organic magnetoelectroluminescence for room temperature transduction between
      magnetic and optical information.
AB  - Magnetic and spin-based technologies for data storage and processing provide
      unique challenges for information transduction to light because of magnetic
      metals' optical loss, and the inefficiency and resistivity of semiconductor spin
      based emitters at room temperature. Transduction between magnetic and optical
      information in typical organic semiconductors poses additional challenges, as the
      spin-orbit interaction is weak and spin injection from magnetic electrodes has
      been limited to low temperature and low polarization efficiency. Here we
      demonstrate room temperature information transduction between a magnet and an
      organic light-emitting diode that does not require electrical current, based on
      control via the magnet's remanent field of the exciton recombination process in
      the organic semiconductor. This demonstration is explained quantitatively within
      a theory of spin-dependent exciton recombination in the organic semiconductor,
      driven primarily by gradients in the remanent fringe fields of a few nanometre
      thick magnetic film. 

PMID- 24736419
TI  - Guidelines for management of asymptomatic ventricular pre-excitation: brave new
      world or Pandora's box?

PMID- 24736420
TI  - Ganglionitis and genetic cardiac arrhythmias: more questions than answers.

PMID- 24736421
TI  - Percutaneous hemodynamic support during scar-ventricular tachycardia ablation: is
      the juice worth the squeeze?

PMID- 24736422
TI  - Where do we come from? Where are we going? Adverse outcomes in catheter ablation
      for atrial fibrillation.

PMID- 24736423
TI  - Is defibrillation testing necessary for implantable transvenous defibrillators?:
      defibrillation testing is necessary at the time of implantable cardioverter
      defibrillator implantation.

PMID- 24736424
TI  - Is defibrillation testing necessary for implantable transvenous defibrillators?:
      defibrillation testing should not be routinely performed at the time of
      implantable cardioverter defibrillator implantation.

PMID- 24736425
TI  - Identical atrio-His interval and A-A intervals during long RP tachycardia: what
      is the mechanism? Diagnosis: Atypical AVNRT.

PMID- 24736426
TI  - Editor's perspective: Atrioventricular nodal reentry tachycardia: chameleon in
      disguise.
AB  - Hayashi et al teach us a sequential approach to question the possibilities that
      explain observed unusual phenomena and demonstrate the importance of finding a
      reasonable ablation target that is safe although the explanation of all
      phenomenon is incomplete. Perhaps future developments of mapping systems and
      novel signal processing presently meant for identifying atrial fibrillation and
      ventricular fibrillation substrate may allow us to record nodal and perinodal
      electrograms to better understand these complex arrhythmias in individual
      patients.

PMID- 24736427
TI  - Entirely subcutaneous implantable defibrillator: safest option in a young girl
      with ventricular tachycardia and Ebstein anomaly.

PMID- 24736428
TI  - Sinus nodal dysfunction after left atrial flutter ablation: a preventable
      complication.

PMID- 24736429
TI  - Letter by Berruezo et al regarding article, "Impact of local ablation on
      interconnected channels within ventricular scar: mechanistic implications for
      substrate modification".

PMID- 24736430
TI  - Response to letter regarding "Impact of local ablation on inter-connected
      channels within ventricular scar: mechanistic implications for substrate
      modification".

PMID- 24736431
TI  - Absence of CD9 reduces endometrial VEGF secretion and impairs uterine repair
      after parturition.
AB  - In mammals, uterine epithelium is remodeled cyclically throughout adult life for
      pregnancy. Despite the expression of CD9 in the uterine epithelium, its role in
      maternal reproduction is unclear. Here, we addressed this issue by examining
      uterine secretions collected from patients undergoing fertility treatment and
      fertilization-competent Cd9(-/-) mice expressing CD9-GFP in their eggs (Cd9(-/
      )TG). CD9 in uterine secretions was observed as extracellular matrix-like
      feature, and its amount of the secretions associated with repeated pregnancy
      failures. We also found that the litter size of Cd9(-/-)TG female mice was
      significantly reduced after their first birth. Severely delayed re
      epithelialization of the endometrium was then occurred. Concomitantly, vascular
      endothelial growth factor (VEGF) was remarkably reduced in the uterine secretions
      of Cd9(-/-)TG female mice. These results provide the first evidence that CD9
      mediated VEGF secretion plays a role in re-epithelialization of the uterus. 

PMID- 24736432
TI  - Vascular regeneration in a basal chordate is due to the presence of immobile, bi
      functional cells.
AB  - The source of tissue turnover during homeostasis or following injury is usually
      due to proliferation of a small number of resident, lineage-restricted stem cells
      that have the ability to amplify and differentiate into mature cell types. We are
      studying vascular regeneration in a chordate model organism, Botryllus
      schlosseri, and have previously found that following surgical ablation of the
      extracorporeal vasculature, new tissue will regenerate in a VEGF-dependent
      process within 48 hrs. Here we use a novel vascular cell lineage tracing
      methodology to assess regeneration in parabiosed individuals and demonstrate that
      the source of regenerated vasculature is due to the proliferation of pre-existing
      vascular resident cells and not a mobile progenitor. We also show that these
      cells are bi-potential, and can reversibly adopt two fates, that of the newly
      forming vessels or the differentiated vascular tissue at the terminus of the
      vasculature, known as ampullae. In addition, we show that pre-existing vascular
      resident cells differentially express progenitor and differentiated cell markers
      including the Botryllus homologs of CD133, VEGFR-2, and Cadherin during the
      regenerative process. 

PMID- 24736433
TI  - p53 modulates Hsp90 ATPase activity and regulates aryl hydrocarbon receptor
      signaling.
AB  - The aryl hydrocarbon receptor (AhR), a client protein of heat shock protein 90
      (Hsp90), is a ligand-activated transcription factor that plays a role in
      polycyclic aromatic hydrocarbon (PAH)-induced carcinogenesis. Tobacco smoke
      activates AhR signaling leading to increased transcription of CYP1A1 and CYP1B1,
      which encode proteins that convert PAHs to mutagens. Recently, p53 was found to
      regulate Hsp90 ATPase activity via effects on activator of Hsp90 ATPase (Aha1).
      It is possible, therefore, that AhR-dependent expression of CYP1A1 and CYP1B1
      might be affected by p53 status. The main objective of this study was to
      determine whether p53 modulated AhR-dependent gene expression and PAH metabolism.
      Here, we show that silencing p53 led to elevated Aha1 levels, increased Hsp90
      ATPase activity, and enhanced CYP1A1 and CYP1B1 expression. Overexpression of
      wild-type p53 suppressed levels of CYP1A1 and CYP1B1. The significance of Aha1 in
      mediating these p53-dependent effects was determined. Silencing of Aha1 led to
      reduced Hsp90 ATPase activity and downregulation of CYP1A1 and CYP1B1. In
      contrast, overexpressing Aha1 was associated with increased Hsp90 ATPase activity
      and elevated levels of CYP1A1 and CYP1B1. Using p53 heterozygous mutant
      epithelial cells from patients with Li-Fraumeni syndrome, we show that
      monoallelic mutation of p53 was associated with elevated levels of CYP1A1 and
      CYP1B1 under both basal conditions and following treatment with benzo[a]pyrene.
      Treatment with CP-31398, a p53 rescue compound, suppressed benzo[a]pyrene
      mediated induction of CYP1A1 and CYP1B1 and the formation of DNA adducts.
      Collectively, our results suggest that p53 affects AhR-dependent gene expression,
      PAH metabolism, and possibly carcinogenesis.

PMID- 24736434
TI  - Identification of Stim1 as a candidate gene for exaggerated sympathetic response
      to stress in the stroke-prone spontaneously hypertensive rat.
AB  - The stroke-prone spontaneously hypertensive rat (SHRSP) is known to have
      exaggerated sympathetic nerve activity to various types of stress, which might
      contribute to the pathogenesis of severe hypertension and stroke observed in this
      strain. Previously, by using a congenic strain (called SPwch1.72) constructed
      between SHRSP and the normotensive Wistar-Kyoto rat (WKY), we showed that a 1.8
      Mbp fragment on chromosome 1 (Chr1) of SHRSP harbored the responsible gene(s) for
      the exaggerated sympathetic response to stress. To further narrow down the
      candidate region, in this study, another congenic strain (SPwch1.71) harboring a
      smaller fragment on Chr1 including two functional candidate genes, Phox2a and
      Ship2, was generated. Sympathetic response to cold and restraint stress was
      compared among SHRSP, SPwch1.71, SPwch1.72 and WKY by three different methods
      (urinary norepinephrine excretion, blood pressure measurement by the telemetry
      system and the power spectral analysis on heart rate variability). The results
      indicated that the response in SPwch1.71 did not significantly differ from that
      in SHRSP, excluding Phox2a and Ship2 from the candidate genes. As the stress
      response in SPwch1.72 was significantly less than that in SHRSP, it was concluded
      that the 1.2-Mbp congenic region covered by SPwch1.72 (and not by SPwch1.71) was
      responsible for the sympathetic stress response. The sequence analysis of 12
      potential candidate genes in this region in WKY/Izm and SHRSP/Izm identified a
      nonsense mutation in the stromal interaction molecule 1 (Stim1) gene of SHRSP/Izm
      which was shared among 4 substrains of SHRSP. A western blot analysis confirmed a
      truncated form of STIM1 in SHRSP/Izm. In addition, the analysis revealed that the
      protein level of STIM1 in the brainstem of SHRSP/Izm was significantly lower when
      compared with WKY/Izm. Our results suggested that Stim1 is a strong candidate
      gene responsible for the exaggerated sympathetic response to stress in SHRSP. 

PMID- 24736435
TI  - Exponential signaling gain at the receptor level enhances signal-to-noise ratio
      in bacterial chemotaxis.
AB  - Cellular signaling systems show astonishing precision in their response to
      external stimuli despite strong fluctuations in the molecular components that
      determine pathway activity. To control the effects of noise on signaling most
      efficiently, living cells employ compensatory mechanisms that reach from simple
      negative feedback loops to robustly designed signaling architectures. Here, we
      report on a novel control mechanism that allows living cells to keep precision in
      their signaling characteristics - stationary pathway output, response amplitude,
      and relaxation time - in the presence of strong intracellular perturbations. The
      concept relies on the surprising fact that for systems showing perfect adaptation
      an exponential signal amplification at the receptor level suffices to eliminate
      slowly varying multiplicative noise. To show this mechanism at work in living
      systems, we quantified the response dynamics of the E. coli chemotaxis network
      after genetically perturbing the information flux between upstream and downstream
      signaling components. We give strong evidence that this signaling system results
      in dynamic invariance of the activated response regulator against multiplicative
      intracellular noise. We further demonstrate that for environmental conditions,
      for which precision in chemosensing is crucial, the invariant response behavior
      results in highest chemotactic efficiency. Our results resolve several puzzling
      features of the chemotaxis pathway that are widely conserved across prokaryotes
      but so far could not be attributed any functional role. 

PMID- 24736436
TI  - Memories of Carl from an improbable friend.

PMID- 24736437
TI  - EJEM Editorial.

PMID- 24736438
TI  - Giant tension bulla.

PMID- 24736439
TI  - The muscle ankyrin repeat proteins CARP, Ankrd2, and DARP are not essential for
      normal cardiac development and function at basal conditions and in response to
      pressure overload.
AB  - Ankrd1/CARP, Ankrd2/Arpp, and Ankrd23/DARP belong to a family of stress inducible
      ankyrin repeat proteins expressed in striated muscle (MARPs). The MARPs are
      homologous in structure and localized in the nucleus where they negatively
      regulate gene expression as well as in the sarcomeric I-band, where they are
      thought to be involved in mechanosensing. Together with their strong induction
      during cardiac disease and the identification of causative Ankrd1 gene mutations
      in cardiomyopathy patients, this suggests their important roles in cardiac
      development, function, and disease. To determine the functional role of MARPs in
      vivo, we studied knockout (KO) mice of each of the three family members. Single
      KO mice were viable and had no apparent cardiac phenotype. We therefore
      hypothesized that the three highly homologous MARP proteins may have redundant
      functions in the heart and studied double and triple MARP KO mice. Unexpectedly,
      MARP triple KO mice were viable and had normal cardiac function both at basal
      levels and in response to mechanical pressure overload induced by transverse
      aortic constriction as assessed by echocardiography and hemodynamic studies.
      Thus, CARP, Ankrd2, and DARP are not essential for normal cardiac development and
      function at basal conditions and in response to mechanical pressure overload. 

PMID- 24736442
TI  - Use of artemisinin and its derivatives for the treatment of malaria in children.

PMID- 24736440
TI  - Pharmacokinetics of zidovudine dosed twice daily according to World Health
      Organization weight bands in Ugandan HIV-infected children.
AB  - Data on zidovudine pharmacokinetics in children dosed using World Health
      Organization weight bands are limited. About 45 HIV-infected, Ugandan children,
      3.4 (2.6-6.2) years, had intensive pharmacokinetic sampling. Geometric mean
      zidovudine AUC0-12h was 3.0 h.mg/L, which is higher than previously observed in
      adults, and was independently higher in those receiving higher doses, younger and
      underweight children. Higher exposure was also marginally associated with lower
      hemoglobin. 

PMID- 24736441
TI  - Tuberculosis Immune Reconstitution Inflammatory Syndrome in children initiating
      Antiretroviral Therapy for HIV infection: A systematic literature review.
AB  - BACKGROUND: People with HIV initiating combination antiretroviral therapy are at
      risk for tuberculosis-associated immune reconstitution inflammatory syndrome (TB
      IRIS). While this syndrome has been well researched in adults, little is known
      about the incidence, case fatality, underlying immunopathology and treatment
      approaches in children. METHODS: Major databases were searched for articles
      related to TB-IRIS in children. Data were abstracted using standardized forms.
      RESULTS: Thirteen studies were identified: 6 retrospective and 2 prospective
      cohort studies, 1 cross-sectional study, 3 case reports and 1 case series. In
      total, 303 cases of TB-IRIS were described, of which 270 were unmasking TB-IRIS,
      12 paradoxical TB-IRIS and 21 were not classifiable due to lack of key
      information. None of the cohort studies had investigation of TB-IRIS as its
      primary aim. Nine studies were from Africa, 3 from Asia and 1 from Latin America.
      Age at cART initiation (reported by 12 studies) ranged from 1 month to 16 years.
      Median time from start of cART to IRIS diagnosis (reported by 8 studies) ranged
      from 8 days to 16 weeks. Few deaths attributable to TB-IRIS were recorded.
      Treatment was only discussed in 2 case studies, both of which reported children
      receiving corticosteroids. No studies evaluated risk factors for, or
      immunopathogenesis of, pediatric TB-IRIS. CONCLUSIONS: There is a paucity of
      information available on TB-IRIS in children. Future research assessing
      incidence, risk factors, case fatality and optimal treatment or prevention
      strategies of TB-IRIS is needed.

PMID- 24736443
TI  - Risk factors for pneumococcal carriage in day care centers: a retrospective study
      during a 10-year period.
AB  - In this retrospective epidemiologic study, we present pneumococcal carriage data
      from 109 Swedish day care centers over a period of 10 years. Aspects of season,
      age, personnel and group size were studied. We found a significant seasonal
      variation in pneumococcal carriage. Group size was a significant risk factor for
      pneumococcal carriage. Pneumococcal carriage was 4.5 % in personnel. 

PMID- 24736444
TI  - Distinct and overlapping functions of ptpn11 genes in Zebrafish development.
AB  - The PTPN11 (protein-tyrosine phosphatase, non-receptor type 11) gene encodes
      SHP2, a cytoplasmic PTP that is essential for vertebrate development. Mutations
      in PTPN11 are associated with Noonan and LEOPARD syndrome. Human patients with
      these autosomal dominant disorders display various symptoms, including short
      stature, craniofacial defects and heart abnormalities. We have used the zebrafish
      as a model to investigate the role of Shp2 in embryonic development. The
      zebrafish genome encodes two ptpn11 genes, ptpn11a and ptpn11b. Here, we report
      that ptpn11a is expressed constitutively and ptpn11b expression is strongly
      upregulated during development. In addition, the products of both ptpn11 genes,
      Shp2a and Shp2b, are functional. Target-selected inactivation of ptpn11a and
      ptpn11b revealed that double homozygous mutants are embryonic lethal at 5-6 days
      post fertilization (dpf). Ptpn11a-/-ptpn11b-/- embryos showed pleiotropic defects
      from 4 dpf onwards, including reduced body axis extension and craniofacial
      defects, which was accompanied by low levels of phosphorylated Erk at 5 dpf.
      Interestingly, defects in homozygous ptpn11a-/- mutants overlapped with defects
      in the double mutants albeit they were milder, whereas ptpn11b-/- single mutants
      did not show detectable developmental defects and were viable and fertile.
      Ptpn11a-/-ptpn11b-/- mutants were rescued by expression of exogenous ptpn11a and
      ptpn11b alike, indicating functional redundance of Shp2a and Shp2b. The ptpn11
      mutants provide a good basis for further unravelling of the function of Shp2 in
      vertebrate development. 

PMID- 24736446
TI  - The nature of persistent conformational chirality, racemization mechanisms, and
      predictions in diarylether heptanoid cyclophane natural products.
AB  - Restricted rotations of chemical bonds can lead to the presence of persistent
      conformational chirality in molecules lacking stereocenters. We report the
      development of first-of-a-kind predictive rules that enable identification of
      conformational chirality and prediction of racemization barriers in the
      diarylether heptanoid (DAEH) natural products that do not possess stereocenters.
      These empirical rules-of-thumb are based on quantum mechanical computations (SCS
      MP2/infinity//B3LYP/6-31G*/PCM) of racemization barriers of four representative
      DAEHs. Specifically, the local symmetry of ring B and the E/Z configuration of
      the vinylogous acid/ester are critical in determining conformational chirality in
      the DAEH natural product family. 

PMID- 24736445
TI  - Absence of metalloprotease GP63 alters the protein content of Leishmania
      exosomes.
AB  - Protozoan parasites of Leishmania genus are able to successfully infect their
      host macrophage due to multiple virulence strategies that result in its
      deactivation. Recent studies suggest Leishmania GP63 to be a critical virulence
      factor in modulation of many macrophage molecules, including protein tyrosine
      phosphatases (PTPs) and transcription factors (TFs). Additionally, we and others
      recently reported that Leishmania-released exosomes can participate in
      pathogenesis. Exosomes are 40-100 nm vesicles that are freed by many eukaryotic
      cells. To better understand the GP63-dependent immune modulation of the
      macrophage by Leishmania parasites and their exosomes, we compared the
      immunomodulatory properties of Leishmania major (WT) and L. major gp63-/- (KO) as
      well as their exosomes in vitro and in vivo. Importantly, we observed that
      Leishmania exosomes can modulate macrophage PTPs and TFs in a GP63-dependent
      manner. In addition, our qRT-PCR analyses showed that WT parasites were able to
      downregulate multiple genes involved in the immune response, especially cytokines
      and pattern recognition receptors. KO parasites showed a strongly reduced
      modulatory capacity compared to WT parasites. Furthermore, comparison of WT
      versus KO exosomes also showed divergences in alteration of gene expression,
      especially of chemokine receptors. In parallel, studying the in vivo inflammatory
      recruitment using a murine air pouch model, we found that exosomes have stronger
      proinflammatory properties than parasites and preferentially induce the
      recruitment of neutrophils. Finally, comparative proteomics of WT and KO exosomes
      surprisingly revealed major differences in their protein content, suggesting a
      role for GP63 in Leishmania exosomal protein sorting. Collectively our data
      clearly establish the crucial role of GP63 in dampening the innate inflammatory
      response during early Leishmania infection, and also provides new insights in
      regard to the role and biology of exosomes in Leishmania host-parasite
      interactions. 

PMID- 24736447
TI  - Self-adhesive mesh for Lichtenstein inguinal hernia repair. Experience of a
      single center.
AB  - AIM: Lichtenstein tension-free mesh repair is the most frequently performed
      procedure for inguinal hernioplasty. In the past surgery aimed to control
      recurrences. Nowadays it is important to avoid postoperative chronic pain and
      thus several studies have examined the potential role of meshes in causing
      postoperative pain. The purpose of this study was to retrospectively assess the
      early and long-term results after Lichtenstein tension-free repair using a self
      adhesive mesh (Parietex ProgripTM - Covidien, Germany) in a single center.
      METHODS: The study enrolled 211 patients, 199 males (94.3%) and 12 females
      (5.7%), mean age 62 years (28-90 years), between January 2008 and December 2011.
      Of these, 206 had primary inguinal hernias while 5 were recurrences following
      previous tension repair. Ten different general surgeons, including residents,
      performed Lichtenstein hernia repair using a 12 x 8-cm Parietex ProgripTM mesh.
      In 88.1% of patients no additional fixation was used, while in 11.9% a single 2-0
      polypropylene stitch was placed on the pubic bone. A 1-10 visual analog scale
      (VAS) was used to assess postoperative pain, evaluating it at 1 week, 1 month and
      12, 24 and 36 months. Local paresthesia was assessed at same intervals. Any pain
      sensation lasting longer than 3 months postoperatively, or requiring injection of
      analgesics was defined as chronic pain. RESULTS: Mean operating time was 64.1
      minutes (SD +/- 21.14). There were no intraoperative complications. Early
      postoperative complications included hematoma-seroma (5.7% cases), superficial
      wound infection (1%), urinary retention (0.5%), and scrotal swelling (1%). The
      main follow-up period was 3 years, although patients operated between 2009 and
      2011 underwent a shorter follow-up. At one-year follow-up, 17 patients reported
      groin discomfort, but did not require analgesics. Three patients reported
      moderate pain, requiring occasional use of oral analgesics, and 2 of these
      described a discontinuous pain mainly during movement. One patient reported
      severe pain requiring local injection of analgesics. At 2-year follow-up, 3
      patients reported groin discomfort. Five of the 17 patients who reported
      discomfort at 1 year were lost to the 2-year follow-up. One patient kept
      reporting a high VAS score (6), though slightly reduced from the previously
      reported at 1-year follow-up. Recurrence was observed in 0.5% at 1 year and in
      2.4% at 2 years. At 3 years only half of the patients (102) were still on follow
      up. Of these, 1 reported mild discomfort and 3 developed hernia recurrence.
      Globally a decrease in pain and local discomfort was observed. No cases of
      seroma, testicular complications or mesh infection were reported at 1-, 2- and 3
      year follow-up. CONCLUSION: Self-gripping mesh for inguinal hernia repair is a
      good and safe option, easy to handle and with a low incidence of chronic pain
      (<3%). A sutureless fixation seems to prevent the development of postoperative
      chronic pain, without increasing recurrence rates. Using a self-adhesive mesh
      also slightly reduce operating times, and costs are lower when compared to
      biological glue used to fix the mesh. In conclusion, our experience with the self
      gripping mesh is limited but positive, randomized clinical trials are warranted
      to confirm our results.

PMID- 24736448
TI  - Reliability of MDCT, with MPR and hydro-CT technique, in resectability and
      lymphnode staging of gastric cancer.
AB  - AIM: The aim of this study was to evaluate the reliability of thin-slice hydro
      multidetector row computed tomography (MDCT) in assessing resectability and lymph
      node staging of gastric cancer. METHODS: Sixty-one patients (37 males, 24
      females; mean age 61 years) with gastric cancer, and whose surgery was planned,
      underwent preoperative abdominopelvic hydro-MDCT at slice thickness of 5 mm. We
      evaluated the tumor stage, depth of tumor invasion into the gastric wall,
      metastasis of lymph node, and presence/absence of distant metastases on the CT
      images produced with multiplanar reconstruction (MPR) and hydro-CT technique. The
      results were compared with pathological and surgical findings. Diagnostic
      accuracy was also analyzed. RESULTS: Of 61 patients with gastric cancer, 6 (14%)
      were inoperable, 45 (68%) were advanced stage, and 10 (16%) were early stage
      gastric cancer patients. The detection rate of the primary tumor was 97% for
      MDCT; the overall accuracy of MDCT in the determination of the depth of invasion
      and serosal involvement when compared with pathological staging were 84% and 95%,
      respectively; the overall accuracy rate in lymph node staging was 73.5%.
      CONCLUSION: MDCT can improve the accuracy of preoperative T and N staging of
      gastric cancer and will contribute to treatment strategies for patients with
      advanced stage gastric cancer.

PMID- 24736449
TI  - Equilibrium and kinetic studies of Cd2+ biosorption by the brown algae Sargassum
      fusiforme.
AB  - A fundamental investigation of the biosorption of Cd2+ from aqueous solution by
      the edible seaweed Sargassum fusiforme was performed under batch conditions. The
      influences of experimental parameters, such as the initial pH, sorption time,
      temperature, and initial Cd2+ concentration, on Cd2+ uptake by S. fusiforme were
      evaluated. The results indicated that the biosorption of Cd2+ depended on the
      initial Cd2+ concentration, as well as the pH. The uptake of Cd2+ could be
      described by the Langmuir isotherm model, and both the Langmuir biosorption
      equilibrium constant and the maximum biosorption capacity of the monolayer
      decreased with increasing temperature, thereby confirming the exothermic
      character of the sorption process. The biosorption kinetics follows the pseudo
      second-order kinetic model, and intraparticle diffusion is the sole rate-limiting
      step for the entire biosorption period. These fundamental equilibrium and kinetic
      results can support further studies to the removal of cadmium from S. fusiforme
      harvested from cadmium-polluted waters.

PMID- 24736451
TI  - Only the chemical state of Indium changes in Mn-doped In3Sb1Te2 (Mn: 10 at.%)
      during multi-level resistance changes.
AB  - We fabricated and characterized the material with Mn (10 at.%: atomic percent)
      doped In3Sb1Te2 (MIST) using co-sputtering and synchrotron radiation,
      respectively. The MIST thin film showed phase-changes at 97 and 320  degrees C,
      with sheet resistances of ~10 kOmega(sq) (amorphous), ~0.2 kOmega(sq) (first
      phase-change), and ~10 Omega(sq) (second phase-change). MIST did not exhibit any
      chemical separation or increased structural instability during either phase
      change, as determined with high-resolution x-ray photoelectron spectroscopy.
      Chemical state changes were only depended for In without concomitant changes of
      Sb and Te. Apparently, doped Mn atoms can be induced with movement of only In
      atoms.

PMID- 24736450
TI  - The early activation of toll-like receptor (TLR)-3 initiates kidney injury after
      ischemia and reperfusion.
AB  - Acute kidney injury (AKI) is one of the most important complications in
      hospitalized patients and its pathomechanisms are not completely elucidated. We
      hypothesize that signaling via toll-like receptor (TLR)-3, a receptor that is
      activated upon binding of double-stranded nucleotides, might play a crucial role
      in the pathogenesis of AKI following ischemia and reperfusion (IR). Male adult
      C57Bl6 wild-type (wt) mice and TLR-3 knock-out (-/-) mice were subjected to 30
      minutes bilateral selective clamping of the renal artery followed by reperfusion
      for 30 min 2.5h and 23.5 hours or subjected to sham procedures. TLR-3 down-stream
      signaling was activated already within 3 h of ischemia and reperfusion in post
      ischemic kidneys of wt mice lead to impaired blood perfusion followed by a strong
      pro-inflammatory response with significant neutrophil invasion. In contrast, this
      effect was absent in TLR-3-/- mice. Moreover, the quick TLR-3 activation resulted
      in kidney damage that was histomorphologically associated with significantly
      increased apoptosis and necrosis rates in renal tubules of wt mice. This finding
      was confirmed by increased kidney injury marker NGAL in wt mice and a better
      preserved renal perfusion after IR in TLR-3-/- mice than wt mice. Overall, the
      absence of TLR-3 is associated with lower cumulative kidney damage and maintained
      renal blood perfusion within the first 24 hours of reperfusion. Thus, we conclude
      that TLR-3 seems to participate in the pathogenesis of early acute kidney injury.

PMID- 24736452
TI  - Influenza epidemiology and vaccine effectiveness among patients with influenza
      like illness, viral watch sentinel sites, South Africa, 2005-2009.
AB  - BACKGROUND: There is limited data on the epidemiology of influenza and few
      published estimates of influenza vaccine effectiveness (VE) from Africa. In April
      2009, a new influenza virus strain infecting humans was identified and rapidly
      spread globally. We compared the characteristics of patients ill with influenza
      A(H1N1)pdm09 virus to those ill with seasonal influenza and estimated influenza
      vaccine effectiveness during five influenza seasons (2005-2009) in South Africa.
      METHODS: Epidemiological data and throat and/or nasal swabs were collected from
      patients with influenza-like illness (ILI) at sentinel sites. Samples were tested
      for seasonal influenza viruses using culture, haemagglutination inhibition tests
      and/or polymerase chain reaction (PCR) and for influenza A(H1N1)pdm09 by real
      time PCR. For the vaccine effectiveness (VE) analysis we considered patients
      testing positive for influenza A and/or B as cases and those testing negative for
      influenza as controls. Age-adjusted VE was calculated as 1-odds ratio for
      influenza in vaccinated and non-vaccinated individuals. RESULTS: From 2005
      through 2009 we identified 3,717 influenza case-patients. The median age was
      significantly lower among patients infected with influenza A(H1N1)pdm09 virus
      than those with seasonal influenza, 17 and 27 years respectively (p<0.001). The
      vaccine coverage during the influenza season ranged from 3.4% in 2009 to 5.1% in
      2006 and was higher in the >=50 years (range 6.9% in 2008 to 13.2% in 2006) than
      in the <50 years age group (range 2.2% in 2007 to 3.7% in 2006). The age-adjusted
      VE estimates for seasonal influenza were 48.6% (4.9%, 73.2%); -14.2% (-9.7%,
      34.8%); 12.0% (-70.4%, 55.4%); 67.4% (12.4%, 90.3%) and 29.6% (-21.5%, 60.1%)
      from 2005 to 2009 respectively. For the A(H1N1)pdm09 season, the efficacy of
      seasonal vaccine was -6.4% (-93.5%, 43.3%). CONCLUSION: Influenza vaccine
      demonstrated a significant protective effect in two of the five years evaluated.
      Low vaccine coverage may have reduced power to estimate vaccine effectiveness.

PMID- 24736454
TI  - Impacts of removing badgers on localised counts of hedgehogs.
AB  - Experimental evidence of the interactions among mammalian predators that eat or
      compete with one another is rare, due to the ethical and logistical challenges of
      managing wild populations in a controlled and replicated way. Here, we report on
      the opportunistic use of a replicated and controlled culling experiment (the
      Randomised Badger Culling Trial) to investigate the relationship between two
      sympatric predators: European badgers Meles meles and western European hedgehogs
      Erinaceus europaeus. In areas of preferred habitat (amenity grassland), counts of
      hedgehogs more than doubled over a 5-year period from the start of badger culling
      (from 0.9 ha-1 pre-cull to 2.4 ha-1 post-cull), whereas hedgehog counts did not
      change where there was no badger culling (0.3-0.3 hedgehogs ha-1). This trial
      provides experimental evidence for mesopredator release as an outcome of
      management of a top predator.

PMID- 24736455
TI  - Thermochemical CO2 splitting via redox cycling of ceria reticulated foam
      structures with dual-scale porosities.
AB  - Efficient heat transfer of concentrated solar energy and rapid chemical kinetics
      are desired characteristics of solar thermochemical redox cycles for splitting
      CO2. We have fabricated reticulated porous ceramic (foam-type) structures made of
      ceria with dual-scale porosity in the millimeter and micrometer ranges. The
      larger void size range, with dmean = 2.5 mm and porosity = 0.76-0.82, enables
      volumetric absorption of concentrated solar radiation for efficient heat transfer
      to the reaction site during endothermic reduction, while the smaller void size
      range within the struts, with dmean = 10 MUm and strut porosity = 0-0.44,
      increases the specific surface area for enhanced reaction kinetics during
      exothermic oxidation with CO2. Characterization is performed via mercury
      intrusion porosimetry, scanning electron microscopy, and thermogravimetric
      analysis (TGA). Samples are thermally reduced at 1773 K and subsequently oxidized
      with CO2 at temperatures in the range 873-1273 K. On average, CO production rates
      are ten times higher for samples with 0.44 strut porosity than for samples with
      non-porous struts. The oxidation rate scales with specific surface area and the
      apparent activation energy ranges from 90 to 135.7 kJ mol(-1). Twenty consecutive
      redox cycles exhibited stable CO production yield per cycle. Testing of the dual
      scale RPC in a solar cavity-receiver exposed to high-flux thermal radiation (3.8
      kW radiative power at 3015 suns) corroborated the superior performance observed
      in the TGA, yielding a shorter cycle time and a mean solar-to-fuel energy
      conversion efficiency of 1.72%. 

PMID- 24736453
TI  - MHC-I expression renders catecholaminergic neurons susceptible to T-cell-mediated
      degeneration.
AB  - Subsets of rodent neurons are reported to express major histocompatibility
      complex class I (MHC-I), but such expression has not been reported in normal
      adult human neurons. Here we provide evidence from immunolabel, RNA expression
      and mass spectrometry analysis of postmortem samples that human catecholaminergic
      substantia nigra and locus coeruleus neurons express MHC-I, and that this
      molecule is inducible in human stem cell-derived dopamine (DA) neurons.
      Catecholamine murine cultured neurons are more responsive to induction of MHC-I
      by gamma-interferon than other neuronal populations. Neuronal MHC-I is also
      induced by factors released from microglia activated by neuromelanin or alpha
      synuclein, or high cytosolic DA and/or oxidative stress. DA neurons internalize
      foreign ovalbumin and display antigen derived from this protein by MHC-I, which
      triggers DA neuronal death in the presence of appropriate cytotoxic T cells.
      Thus, neuronal MHC-I can trigger antigenic response, and catecholamine neurons
      may be particularly susceptible to T-cell-mediated cytotoxic attack. 

PMID- 24736456
TI  - The C-terminal SH3 domain contributes to the intramolecular inhibition of Vav
      family proteins.
AB  - Vav proteins are phosphorylation-dependent guanine nucleotide exchange factors
      (GEFs) that catalyze the activation of members of the Rho family of guanosine
      triphosphatases (GTPases). The current regulatory model holds that the
      nonphosphorylated, catalytically inactive state of these GEFs is maintained by
      intramolecular interactions among the amino-terminal domains and the central
      catalytic core, which block the binding of Vav proteins to GTPases. We showed
      that this autoinhibition is mechanistically more complex, also involving the
      bivalent association of the carboxyl-terminal Src homology 3 (SH3) region of Vav
      with its catalytic and pleckstrin homology (PH) domains. Such interactions
      occurred through proline-rich region-independent mechanisms. Full release from
      this double-locked state required synergistic weakening effects from multiple
      phosphorylated tyrosine residues, thus providing an optimized system to generate
      gradients of Vav GEF activity depending on upstream signaling inputs. This
      mechanism is shared by mammalian and Drosophila melanogaster Vav proteins,
      suggesting that it may be a common regulatory feature for this protein family. 

PMID- 24736458
TI  - Antibiotics to promote growth in children?

PMID- 24736459
TI  - Autoimmune polyglandular type IIIc syndrome associated with Vogt-Koyanagi-Harada
      syndrome and common variable immunodeficiency.

PMID- 24736457
TI  - Intronic miR-3151 within BAALC drives leukemogenesis by deregulating the TP53
      pathway.
AB  - The BAALC/miR-3151 locus on chromosome 8q22 contains both the BAALC gene (for
      brain and acute leukemia, cytoplasmic) and miR-3151, which is located in intron 1
      of BAALC. Older acute myeloid leukemia (AML) patients with high expression of
      both miR-3151 and the BAALC mRNA transcript have a low survival prognosis, and
      miR-3151 and BAALC expression is associated with poor survival independently of
      each other. We found that miR-3151 functioned as the oncogenic driver of the
      BAALC/miR-3151 locus. Increased production of miR-3151 reduced the apoptosis and
      chemosensitivity of AML cell lines and increased leukemogenesis in mice.
      Disruption of the TP53-mediated apoptosis pathway occurred in leukemia cells
      overexpressing miR-3151 and the miR-3151 bound to the 3' untranslated region of
      TP53. In contrast, BAALC alone had only limited oncogenic activity. We found that
      miR-3151 contains its own regulatory element, thus partly uncoupling miR-3151
      expression from that of the BAALC transcript. Both genes were bound and
      stimulated by a complex of the transcription factors SP1 and nuclear factor
      kappaB (SP1/NF-kappaB). Disruption of SP1/NF-kappaB binding reduced both miR-3151
      and BAALC expression. However, expression of only BAALC, but not miR-3151, was
      stimulated by the transcription factor RUNX1, suggesting a mechanism for the
      partly discordant expression of miR-3151 and BAALC observed in AML patients.
      Similar to the AML cells, in melanoma cell lines, overexpression of miR-3151
      reduced the abundance of TP53, and knockdown of miR-3151 increased caspase
      activity, whereas miR-3151 overexpression reduced caspase activity. Thus, this
      oncogenic miR-3151 may also have a role in solid tumors. 

PMID- 24736460
TI  - Iterative development of visual control systems in a research vivarium.
AB  - The goal of this study was to test the hypothesis that reintroduction of
      Continuous Performance Improvement (CPI) methodology, a lean approach to
      management at Seattle Children's (Hospital, Research Institute, Foundation),
      would facilitate engagement of vivarium employees in the development and
      sustainment of a daily management system and a work-in-process board. Such
      engagement was implemented through reintroduction of aspects of the Toyota
      Production System. Iterations of a Work-In-Process Board were generated using
      Shewhart's Plan-Do-Check-Act process improvement cycle. Specific attention was
      given to the importance of detecting and preventing errors through assessment of
      the following 5 levels of quality: Level 1, customer inspects; Level 2, company
      inspects; Level 3, work unit inspects; Level 4, self-inspection; Level 5, mistake
      proofing. A functioning iteration of a Mouse Cage Work-In-Process Board was
      eventually established using electronic data entry, an improvement that increased
      the quality level from 1 to 3 while reducing wasteful steps, handoffs and queues.
      A visual workplace was realized via a daily management system that included a
      Work-In-Process Board, a problem solving board and two Heijunka boards. One
      Heijunka board tracked cage changing as a function of a biological kanban, which
      was validated via ammonia levels. A 17% reduction in cage changing frequency
      provided vivarium staff with additional time to support Institute researchers in
      their mutual goal of advancing cures for pediatric diseases. Cage washing metrics
      demonstrated an improvement in the flow continuum in which a traditional batch
      and queue push system was replaced with a supermarket-type pull system. Staff
      engagement during the improvement process was challenging and is discussed. The
      collective data indicate that the hypothesis was found to be true. The
      reintroduction of CPI into daily work in the vivarium is consistent with the 4P
      Model of the Toyota Way and selected Principles that guide implementation of the
      Toyota Production System. 

PMID- 24736461
TI  - MLL fusion-driven activation of CDK6 potentiates proliferation in MLL-rearranged
      infant ALL.
AB  - Acute lymphoblastic leukemia in infants (< 1 year-of-age) is characterized by a
      high incidence of MLL rearrangements. Recently, direct targets of the MLL fusion
      protein have been identified. However, functional validation of the identified
      targets remained unacknowledged. In this study, we identify CDK6 as a direct
      target of the MLL fusion protein and an important player in the proliferation
      advantage of MLL-rearranged leukemia. CDK6 mRNA was significantly higher
      expressed in MLL-rearranged infant ALL patients compared with MLL wild-type ALL
      patients (P < 0.001). Decrease of MLL-AF4 and MLL-ENL fusion mRNA expression by
      siRNAs resulted in downregulation of CDK6, affirming a direct relationship
      between the presence of the MLL fusion and CDK6 expression. Knockdown of CDK6
      itself significantly inhibited proliferation in the MLL-AF4-positive cell line
      SEM, whereas knockdown of the highly homologous gene CDK4 had virtually no effect
      on the cell cycle. Furthermore, we show in vitro sensitivity of MLL-rearranged
      leukemia cell lines to the CDK4/6-inhibitor PD0332991, inducing a remarkable G 1
      arrest, and downregulation of its downstream targets pRB1 and EZH2. We therefore
      conclude that CDK6 is indeed a direct target of MLL fusion proteins, playing an
      important role in the proliferation advantage of MLL-rearranged ALL cells. 

PMID- 24736462
TI  - Endothelial progenitor cells and response to ranibizumab in age-related macular
      degeneration.
AB  - BACKGROUND: Choroidal neovascularization (CNV) is the main cause of vision loss
      in age-related macular degeneration (AMD). In experimental CNV, endothelial
      progenitor cells (EPCs) contribute to the formation of new vessels. The aim of
      this study was to investigate whether the behavior of EPCs in patients with AMD
      supports a role for EPCs in human CNV. METHODS: The number of circulating EPCs
      that are considered pure endothelial precursors and EPCs with monocytic
      characteristics, and the plasma levels of regulatory cytokines were evaluated in
      23 patients with AMD with active CNV and 20 matched controls. In the patients,
      this profile was re-evaluated after ranibizumab. RESULTS: When compared with
      controls, the patients with AMD showed a lower number of both EPC types (P =
      0.03) and higher plasma levels (P = 0.03) of stromal cell-derived factor 1. Three
      monthly injections of ranibizumab returned to control levels the number of
      circulating EPCs considered pure endothelial precursors and of stromal cell
      derived factor 1, but not of monocytic EPCs. CONCLUSION: The observations
      indicate responsiveness of circulating EPCs to the CNV process in AMD. They
      suggest the hypothesis that increased stromal cell-derived factor 1 production at
      the CNV site (reflected in higher plasma levels) recruits EPCs from the
      circulation, and that antivascular endothelial growth factor therapy selectively
      decreases the recruitment of cells to be incorporated into new vessels.

PMID- 24736463
TI  - Hyperreflective pyramidal structures on optical coherence tomography in
      geographic atrophy areas.
AB  - PURPOSE: We observed hyperreflective dome-shaped or pyramidal structures (HPS) on
      spectral domain optical coherence tomography (SD-OCT) in patients affected with
      geographic atrophy (GA). Our purpose was to describe the multimodal imaging
      features of HPS identified in areas of GA in patients with age-related macular
      degeneration. METHODS: This is a retrospective case series of patients with GA
      harboring HPS in atrophic areas. Multimodal imaging examination including
      infrared reflectance, fundus autofluorescence, and SD-OCT, was performed for each
      patient. Infrared and fundus autofluorescence appearance and mean SD-OCT height
      of HPS in GA were analyzed. RESULTS: A total of 36 eyes of 25 patients (20 women;
      mean age, 82.3 +/- 5.9 years, range, 73-92 years) with GA were included. A total
      of 96 HPS in GA were analyzed by SD-OCT. In all HPS (96/96, 100%), the peripheral
      part was hyperreflective. In 66 of 96 HPS (69%), the center was heterogeneously
      hyperreflective, whereas in 30 of 96 HPS (31%), the center was hyporeflective. On
      infrared reflectance images, HPS in GA appeared as hyporeflective lesions
      surrounded by hyperreflective halos, within an area of background
      hyperreflectivity because of GA in all eyes. On fundus autofluorescence, 39 of 96
      HPS (41%) were heterogeneously hyperautofluorescent, whereas 57 of 96 HPS (59%)
      were hypoautofluorescent. Mean height of HPS was 91 +/- 50.9 MUm in the foveal
      scan (range, 42-291 MUm). CONCLUSION: We describe a multimodal imaging of
      distinctive lesions that presented as hyperreflective pyramidal structures on SD
      OCT. We suggest the name "ghost drusen" because these HPS appear in GA areas, and
      because of their pyramidal or dome-shaped aspect on SD-OCT.

PMID- 24736464
TI  - Comparison of morphologic features of macular proliferative vitreoretinopathy and
      idiopathic epimacular membrane.
AB  - BACKGROUND: To compare the spectral-domain optical coherence tomography
      morphologic features and visual characteristics of a series of patients with
      epimacular membrane with and without a history of retinal breaks. METHODS:
      Prospective, comparative case series of patients with epimacular membrane. All
      patients were evaluated with spectral-domain optical coherence tomography and
      detailed peripheral retinal examination. Symptomatic patients were treated with
      pars plana vitrectomy and epimacular membrane removal based on standard visual
      criteria. RESULTS: Macular proliferative vitreoretinopathy was present in 21 of
      50 patients (42%). Approximately 18 of 21 patients had a previous retinal break,
      5 of which were untreated before the initial examination. No retinal breaks were
      observed in the idiopathic group. Macular proliferative vitreoretinopathy was
      highly associated with a history of retinal breaks (P < 0.001). Presenting visual
      acuity was significantly worse (mean, 0.86 +/- 0.44) for macular proliferative
      vitreoretinopathy than for the idiopathic group (mean, 0.44 +/- 0.36).
      CONCLUSION: Epimacular membrane occurring in the context of previous retinal
      breaks or macular proliferative vitreoretinopathy has a characteristic
      morphologic feature in spectral-domain optical coherence tomography. Surgical
      removal typically results in significant visual improvement.

PMID- 24736465
TI  - Intraocular pressure elevation after uncomplicated pars plana vitrectomy: results
      of the Pan American Collaborative Retina Study Group.
AB  - PURPOSE: To compare the incident rates of sustained elevation of intraocular
      pressure (IOP) after uncomplicated pars plana vitrectomy for idiopathic
      epiretinal membrane and the unoperated fellow eye. METHODS: Retrospective
      multicenter study of 198 patients who underwent pars plana vitrectomy for an
      idiopathic epiretinal membrane that was followed for at least 12 months. The
      diagnosis of sustained IOP elevation was defined as an elevation of IOP >= 24
      mmHg or an increase of >= 5 mmHg in the IOP from baseline on 2 separate visits
      that warranted the initiation of ocular hypotensive therapy. The main outcome
      measured was the development of sustained IOP elevation as defined above.
      RESULTS: Patients were followed for an average of 47.3 +/- 24 months (range, 12
      106 months). In the vitrectomized eyes, 38 of the 198 (19.2%) patients developed
      elevated IOP compared with 9 of the 198 (4.5%) unoperated fellow eyes (P <
      0.0001, Fisher exact test; odds ratio, 4.988). Possible risk factors include a
      family history of open-angle glaucoma (P = 0.0004 Fisher exact test; odds ratio,
      7.206) and cataract surgery (P = 0.0270 Fisher exact test; odds ratio, 2.506).
      CONCLUSION: Uncomplicated PPV seems to increase the IOP, particularly in those
      who are pseudophakic and have a family history of open-angle glaucoma. This
      increase in IOP may lead to glaucomatous damage if not managed appropriately.
      Patients with a previous PPV need to be followed by an ophthalmologist to monitor
      the IOP in the vitrectomized eye.

PMID- 24736466
TI  - Duck enteritis virus glycoprotein D and B DNA vaccines induce immune responses
      and immunoprotection in Pekin ducks.
AB  - DNA vaccine is a promising strategy for protection against virus infection.
      However, little is known on the efficacy of vaccination with two plasmids for
      expressing the glycoprotein D (gD) and glycoprotein B (gB) of duck enteritis
      virus (DEV) in inducing immune response and immunoprotection against virulent
      virus infection in Pekin ducks. In this study, two eukaryotic expressing plasmids
      of pcDNA3.1-gB and pcDNA3.1-gD were constructed. Following transfection, the gB
      and gD expressions in DF1 cells were detected. Groups of ducks were vaccinated
      with pcDNA3.1-gB and/or pcDNA3.1-gD, and boosted with the same vaccine on day 14
      post primary vaccination. We found that intramuscular vaccinations with pcDNA3.1
      gB and/or pcDNA3.1-gD, but not control plasmid, stimulated a high frequency of
      CD4+ and CD8+ T cells in Pekin ducks, particularly with both plasmids. Similarly,
      vaccination with these plasmids, particularly with both plasmids, promoted higher
      levels of neutralization antibodies against DEV in Pekin ducks. More importantly,
      vaccination with both plasmids significantly reduced the virulent DEV-induced
      mortality in Pekin ducks. Our data indicated that vaccination with plasmids for
      expressing both gB and gD induced potent cellular and humoral immunity against
      DEV in Pekin ducks. Therefore, this vaccination strategy may be used for the
      prevention of DEV infection in Pekin ducks. 

PMID- 24736468
TI  - Air versus ground transport of patients with acute myocardial infarction:
      experience in a rural-based helicopter medical service.
AB  - AIMS: Primary prehospital Helicopter Emergency Medical Service (HEMS)
      interventions may play a role in timely reperfusion therapy for patients with ST
      segment elevation myocardial infarction (STEMI). We designed a prospective study
      involving patients with acute myocardial infarction aimed at the evaluation of
      the potential benefit of such primary HEMS interventions as compared with
      classical Emergency Medical Services ground transport. METHODS AND RESULTS: This
      prospective study was conducted from 1 July 2007 to 15 June 2012. Successive
      patients with STEMI eligible for percutaneous coronary intervention were
      included. Simulated ground-based access times were computed using a digital
      cartographic program, allowing the estimation of healthcare system delay from
      call to admission to the catheterization laboratory.During the study period, 4485
      patients benefited from HEMS activations. Of these patients, 342 (8%) suffering
      from STEMI were transferred for primary percutaneous coronary intervention. The
      median primary response time was 11 min (interquartile range: 8-14 min) using the
      helicopter and 32 min (25-44 min) using road transport. The median transport time
      was 12 min (9-15 min) using HEMS and 50 min (36-56 min) by road. The median
      system delay using HEMS was 52 min (45-60 min), whereas this time was 110 min (95
      126 min) by road. Finally, the system delay median gain was 60 min (47-72 min).
      CONCLUSION: Using HEMS in a rural region allows STEMI patients to benefit from
      appropriate rescue care with delays similar to those seen in urban settings.

PMID- 24736467
TI  - Nitroheterocyclic compounds are more efficacious than CYP51 inhibitors against
      Trypanosoma cruzi: implications for Chagas disease drug discovery and
      development.
AB  - Advocacy for better drugs and access to treatment has boosted the interest in
      drug discovery and development for Chagas disease, a chronic infection caused by
      the genetically heterogeneous parasite, Trypanosoma cruzi. In this work new in
      vitro assays were used to gain a better understanding of the antitrypanosomal
      properties of the most advanced antichagasic lead and clinical compounds, the
      nitroheterocyclics benznidazole, nifurtimox and fexinidazole sulfone, the
      oxaborole AN4169, and four ergosterol biosynthesis inhibitors--posaconazole,
      ravuconazole, EPL-BS967 and EPL-BS1246. Two types of assays were developed: one
      for evaluation of potency and efficacy in dose-response against a panel of T.
      cruzi stocks representing all current discrete typing units (DTUs), and a time
      kill assay. Although less potent, the nitroheterocyclics and the oxaborole showed
      broad efficacy against all T. cruzi tested and were rapidly trypanocidal, whilst
      ergosterol biosynthesis inhibitors showed variable activity that was both
      compound- and strain-specific, and were unable to eradicate intracellular
      infection even after 7 days of continuous compound exposure at most efficacious
      concentrations. These findings contest previous reports of variable responses to
      nitroderivatives among different T. cruzi strains and further challenge the
      introduction of ergosterol biosynthesis inhibitors as new single chemotherapeutic
      agents for the treatment of Chagas disease.

PMID- 24736469
TI  - Epidemiology of treated attention-deficit/hyperactivity disorder (ADHD) across
      the lifespan in Taiwan: a nationwide population-based longitudinal study.
AB  - OBJECTIVES: We used insurance claims of a nationally representative population
      based cohort to assess the longitudinal treated prevalence and incidence of
      attention-deficit/hyperactivity disorder (ADHD) in children, adolescents and
      adults. METHODS: Participants were identified from among National Health
      Insurance enrollees in Taiwan from 1999 to 2005. We identified study subjects who
      had at least one service claim during these years with a principal diagnosis of
      ADHD. A total of 6,173 patients were recorded in the treated ADHD cohort during
      the 6-year study. RESULTS: There was a significant increase in the treated
      prevalence rate of ADHD during the study period, from 64.65 per 100,000 in 2000
      to 145.40 per 100,000 in 2005 (p = .001). An increase in the treated incidence
      rate of ADHD, from 44.67 per 100,000 in 2000 to 81.20 per 100,000 in 2005, was
      also observed (p = .013). However, the treated prevalence of ADHD was still lower
      than that of the community data in Taiwan. The peak treated prevalence of ADHD
      was at age 7-12 years for both males and females, and the peak treated incidence
      of ADHD was at age 0-6 for females and age 7-12 for males. Overall, the treated
      incidence and prevalence rates dropped abruptly after age 13-18 (both p<.001) for
      males and females (p<.001 for both). Male vs. female ratios of treated prevalence
      and incidence were both above 1 before age 25-30 years, but below 1 thereafter.
      CONCLUSION: Although an increasing number of people with ADHD sought treatment
      during 1999-2005 in Taiwan, the treated prevalence of ADHD was still lower than
      that of the community data. The treated incidence and prevalence of ADHD fell
      dramatically after age 13-18. However, more women than men sought treatment in
      adulthood. There may be under-diagnosis and under-treatment of ADHD, especially
      among females and adults.

PMID- 24736470
TI  - Visualization of exciton transport in ordered and disordered molecular solids.
AB  - Transport of nanoscale energy in the form of excitons is at the core of
      photosynthesis and the operation of a wide range of nanostructured optoelectronic
      devices such as solar cells, light-emitting diodes and excitonic transistors. Of
      particular importance is the relationship between exciton transport and nanoscale
      disorder, the defining characteristic of molecular and nanostructured materials.
      Here we report a spatial, temporal and spectral visualization of exciton
      transport in molecular crystals and disordered thin films. Using tetracene as an
      archetype molecular crystal, the imaging reveals that exciton transport occurs by
      random walk diffusion, with a transition to subdiffusion as excitons become
      trapped. By controlling the morphology of the thin film, we show that this
      transition to subdiffusive transport occurs at earlier times as disorder is
      increased. Our findings demonstrate that the mechanism of exciton transport
      depends strongly on the nanoscale morphology, which has wide implications for the
      design of excitonic materials and devices. 

PMID- 24736471
TI  - Diabetes mellitus, smoking status, and rate of sputum culture conversion in
      patients with multidrug-resistant tuberculosis: a cohort study from the country
      of Georgia.
AB  - INTRODUCTION: Diabetes mellitus (DM) is a risk factor for active tuberculosis
      (TB) but little is known about the effect of DM on culture conversion among
      patients with multidrug-resistant (MDR)-TB. The primary aim was to estimate the
      association between DM and rate of TB sputum culture conversion. A secondary
      objective was to estimate the association between DM and the risk of poor
      treatment outcomes among patients with MDR-TB. MATERIALS AND METHODS: A cohort of
      all adult patients starting MDR-TB treatment in the country of Georgia between
      2009-2011 was followed during second-line TB therapy. Cox proportional models
      were used to estimate the adjusted hazard rate of sputum culture conversion. Log
      binomial regression models were used to estimate the cumulative risk of poor TB
      treatment outcome. RESULTS: Among 1,366 patients with sputum culture conversion
      information, 966 (70.7%) had culture conversion and the median time to conversion
      was 68 days (interquartile range 50-120). The rate of conversion was similar
      among patients with MDR-TB and DM (adjusted hazard ratio [aHR] 0.95, 95%CI 0.71
      1.28) compared to patients with MDR-TB only. The rate of culture conversion was
      significantly less in patients that currently smoked (aHR 0.82, 95%CI 0.71-0.95),
      had low body mass index (aHR 0.71, 95%CI 0.59-0.84), second-line resistance (aHR
      0.56, 95%CI 0.43-0.73), lung cavities (aHR 0.70, 95%CI 0.59-0.83) and with
      disseminated TB (aHR 0.75, 95%CI 0.62-0.90). The cumulative risk of poor
      treatment outcome was also similar among TB patients with and without DM
      (adjusted risk ratio [aRR] 1.03, 95%CI 0.93-1.14). CONCLUSIONS: In adjusted
      analyses, DM did not impact culture conversion rates in a clinically meaningful
      way but smoking did.

PMID- 24736472
TI  - Weight at birth and subsequent fecundability: a prospective cohort study.
AB  - OBJECTIVE: To examine the association between a woman's birth weight and her
      subsequent fecundability. METHOD: In this prospective cohort study, we included
      2,773 Danish pregnancy planners enrolled in the internet-based cohort study
      "Snart-Gravid", conducted during 2007-2012. Participants were 18-40 years old at
      study entry, attempting to conceive, and were not receiving fertility treatment.
      Data on weight at birth were obtained from the Danish Medical Birth Registry and
      categorized as <2,500 grams, 2,500-2,999 grams, 3,000-3,999 grams, and >= 4,000
      grams. In additional analyses, birth weight was categorized according to z-scores
      for each gestational week at birth. Time-to-pregnancy measured in cycles was used
      to compute fecundability ratios (FR) and 95% confidence intervals (CI), using a
      proportional probabilities regression model. RESULTS: Relative to women with a
      birth weight of 3,000-3,999 grams, FRs adjusted for gestational age, year of
      birth, and maternal socio-demographic and medical factors were 0.99 (95% CI:
      0.73;1.34), 0.99 (95% CI: 0.87;1.12), and 1.08 (95% CI: 0.94;1.24) for birth
      weight <2,500 grams, 2,500-2,999 grams, and >= 4,000 grams, respectively.
      Estimates remained unchanged after further adjustment for markers of the
      participant's mother's fecundability. We obtained similar results when we
      restricted to women who were born at term, and to women who had attempted to
      conceive for a maximum of 6 cycles before study entry. Results remained similar
      when we estimated FRs according to z-scores of birth weight. CONCLUSION: Our
      results indicate that birth weight appears not to be an important determinant of
      fecundability.

PMID- 24736473
TI  - Human Wharton's Jelly Mesenchymal Stem Cells plasticity augments scar-free skin
      wound healing with hair growth.
AB  - Human mesenchymal stem cells (MSCs) are a promising candidate for cell-based
      transplantation and regenerative medicine therapies. Thus in the present study
      Wharton's Jelly Mesenchymal Stem Cells (WJ-MSCs) have been derived from extra
      embryonic umbilical cord matrix following removal of both arteries and vein.
      Also, to overcome the clinical limitations posed by fetal bovine serum (FBS)
      supplementation because of xenogeneic origin of FBS, usual FBS cell culture
      supplement has been replaced with human platelet lysate (HPL). Apart from general
      characteristic features of bone marrow-derived MSCs, wharton jelly-derived MSCs
      have the ability to maintain phenotypic attributes, cell growth kinetics, cell
      cycle pattern, in vitro multilineage differentiation plasticity, apoptotic
      pattern, normal karyotype-like intrinsic mesenchymal stem cell properties in long
      term in vitro cultures. Moreover, the WJ-MSCs exhibited the in vitro multilineage
      differentiation capacity by giving rise to differentiated cells of not only
      mesodermal lineage but also to the cells of ectodermal and endodermal lineage.
      Also, WJ-MSC did not present any aberrant cell state upon in vivo transplantation
      in SCID mice and in vitro soft agar assays. The immunomodulatory potential
      assessed by gene expression levels of immunomodulatory factors upon exposure to
      inflammatory cytokines in the fetal WJ-MSCs was relatively higher compared to
      adult bone marrow-derived MSCs. WJ-MSCs seeded on decellularized amniotic
      membrane scaffold transplantation on the skin injury of SCID mice model
      demonstrates that combination of WJ-MSCs and decellularized amniotic membrane
      scaffold exhibited significantly better wound-healing capabilities, having
      reduced scar formation with hair growth and improved biomechanical properties of
      regenerated skin compared to WJ-MSCs alone. Further, our experimental data
      indicate that indocyanin green (ICG) at optimal concentration can be
      resourcefully used for labeling of stem cells and in vivo tracking by near
      infrared fluorescence non-invasive live cell imaging of labelled transplanted
      cells, thus proving its utility for therapeutic applications. 

PMID- 24736475
TI  - High-risk HPV nucleic acid detection kit-the careHPV test -a new detection method
      for screening.
AB  - This study assessed the clinical accuracy of the correlation between the careHPV
      test and the HC2 test, as well as the correlation between the careHPV test and
      the HPV-PCR test. From September 21 to December 31, 2009, 419 cervical specimens
      from women, 30-49 years, were collected. All women were assessed by Digene HC2
      High-Risk HPV DNA Test (HC2), careHPV test, and HPV-PCR. The concordance rate
      between careHPV and HC2 was 93.81% and between careHPV and HPV-PCR 88.12%. The
      sensitivity and specificity of the careHPV test to detect cancers of equal or
      greater severity than CIN 2 were 85.71% and 83.15% respectively. Results from
      careHPV, HC2, and HPV-PCR were highly consistent. The careHPV test has good
      sensitivity and specificity for the detection of HPV infection and is a promising
      primary screening method for cervical cancer in low-resource regions. 

PMID- 24736474
TI  - CAM use in pediatric neurology: an exploration of concurrent use with
      conventional medicine.
AB  - BACKGROUND: Previous studies have found that up to 60% of children with
      neurologic conditions have tried complementary and alternative medicine (CAM).
      OBJECTIVE: To assess the use of CAM among patients presenting to neurology
      clinics at two academic centers in Canada. METHODS: A survey instrument was
      developed to inquire about use of CAM products and therapies, including reasons
      for use, perceived helpfulness, and concurrent use with conventional medicine,
      and administered to patients or their parents/guardians at the Stollery
      Children's Hospital in Edmonton and the Children's Hospital of Eastern Ontario
      (CHEO) in Ottawa. RESULTS: Overall CAM use at the Stollery was 78%, compared to
      48% at CHEO. The most common CAM products used were multi-vitamins (84%), vitamin
      C (37%), homeopathic remedies (24%), and fish oil/omega 3 s (22%). The most
      common CAM practices used were massage (47%), chiropractic (37%), faith healing
      (18%), aromatherapy (16%), homeopathy (16%), and relaxation (16%). Many patients
      used CAM products at the same time as conventional medicine but just over half
      (57%) discussed this concurrent use with their physician. CONCLUSION: CAM use is
      common in pediatric neurology patients and most respondents felt that it was
      helpful, with few or no harms associated. However, this use is often undisclosed,
      increasing possibility of interactions with conventional drugs. We urge
      clinicians to inquire about CAM use during routine history taking at every
      patient visit. Parents would clearly like more information about CAM from their
      specialty clinics; such information would be easier to share if more primary data
      were available about the safety and effectiveness of commonly used therapies.

PMID- 24736476
TI  - Automated protein turnover calculations from 15N partial metabolic labeling LC/MS
      shotgun proteomics data.
AB  - Protein turnover is a well-controlled process in which polypeptides are
      constantly being degraded and subsequently replaced with newly synthesized
      copies. Extraction of composite spectral envelopes from complex LC/MS shotgun
      proteomics data can be a challenging task, due to the inherent complexity of
      biological samples. With partial metabolic labeling experiments this complexity
      increases as a result of the emergence of additional isotopic peaks. Automated
      spectral extraction and subsequent protein turnover calculations enable the
      analysis of gigabytes of data within minutes, a prerequisite for systems biology
      high throughput studies. Here we present a fully automated method for protein
      turnover calculations from shotgun proteomics data. The approach enables the
      analysis of complex shotgun LC/MS 15N partial metabolic labeling experiments.
      Spectral envelopes of 1419 peptides can be extracted within an hour. The method
      quantifies turnover by calculating the Relative Isotope Abundance (RIA), which is
      defined as the ratio between the intensity sum of all heavy (15N) to the
      intensity sum of all light (14N) and heavy peaks. To facilitate this process, we
      have developed a computer program based on our method, which is freely available
      to download at http://promex.pph.univie.ac.at/protover. 

PMID- 24736477
TI  - Correction: sharp bounds and normalization of Wiener-type indices.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0078448.]. 

PMID- 24736478
TI  - Real time live imaging of phytopathogenic bacteria Xanthomonas campestris pv.
      campestris MAFF106712 in 'plant sweet home'.
AB  - Xanthomonas is one of the most widespread phytobacteria, causing diseases on a
      variety of agricultural plants. To develop novel control techniques, knowledge of
      bacterial behavior inside plant cells is essential. Xanthomonas campestris pv.
      campestris, a vascular pathogen, is the causal agent of black rot on leaves of
      Brassicaceae, including Arabidopsis thaliana. Among the X. campestris pv.
      campestris stocks in the MAFF collection, we selected XccMAFF106712 as a model
      compatible pathogen for the A. thaliana reference ecotype Columbia (Col-0). Using
      modified green fluorescent protein (AcGFP) as a reporter, we observed real time
      XccMAFF106712 colonization in planta with confocal microscopy. AcGFP-expressing
      bacteria colonized the inside of epidermal cells and the apoplast, as well as the
      xylem vessels of the vasculature. In the case of the type III mutant, bacteria
      colonization was never detected in the xylem vessel or apoplast, though they
      freely enter the xylem vessel through the wound. After 9 days post inoculation
      with XccMAFF106712, the xylem vessel became filled with bacterial aggregates.
      This suggests that Xcc colonization can be divided into main four steps, (1)
      movement in the xylem vessel, (2) movement to the next cell, (3) adhesion to the
      host plant cells, and (4) formation of bacterial aggregates. The type III mutant
      abolished at least steps (1) and (2). Better understanding of Xcc colonization is
      essential for development of novel control techniques for black rot. 

PMID- 24736479
TI  - Use of ultrasound in the haemodynamic assessment of the sick neonate.
AB  - Clinician performed ultrasound (CPU) by the clinician caring for a sick patient
      is increasingly used in critical care specialties. The real-time haemodynamic
      information obtained helps the clinician to understand underlying physiology,
      target treatment and refine clinical decision-making. Neonatologists are
      increasingly using ultrasound to assess sick neonates with a range of clinical
      presentations and demand for training and accreditation programmes is increasing.
      This review discusses the current expanded uses for CPU in the haemodynamic
      assessment of the sick neonate.

PMID- 24736480
TI  - Implementation and execution of military forward resuscitation programs.

PMID- 24736481
TI  - Implementation and execution of military forward resuscitation programs: reply.

PMID- 24736482
TI  - Autosomal dominant policystic kidney disease, more than a renal disease.
AB  - Autosomal dominant polycystic kidney disease (ADPKD) is a systemic disorder
      mainly involving the kidney. It affects one in 400-1000 live births. Early
      hypertension and progressive renal failure due to massive enlargement of cysts
      and fibrosis are hallmarks of the disease. ADPKD accounts for ~5-10% of cases
      requiring renal replacement therapy. But not only the kidneys are affected in
      ADPKD: cysts also occur in other organs such as the liver, pancreas, arachnoid
      membrane and seminal vesicles. Non-cystic manifestations of the diseases are
      intracranial aneurysms, hernias and valvular abnormalities. Complications in
      ADPKD usually result from kidney involvement and include cyst bleeding and cyst
      infection. However, serious extrarenal features such as subarachnoid haemorrhage
      can also occur. There is no specific treatment for ADPKD currently, but many
      molecules targeting up- or downregulated molecules in the renal epithelial cells
      are being tested. A clinical trial using tolvaptan (a vasopressin receptor
      antagonist) has demonstrated efficacy, while mTOR inhibitors have shown no
      positive effect in ADPKD. ACEIs and ARBs are the drugs of choice for treating
      hypertension in ADPKD. Until a specific therapy becomes available, early
      treatment of hypertension and lifestyle changes are encouraged. 

PMID- 24736483
TI  - Plasma GDF-15 levels and their association with hormonal and metabolic status in
      women with polycystic ovary syndrome aged 25-35.
AB  - AIM: We aimed to determine plasma levels of growth differentiation factor (GDF)
      15 and their possible association with hormonal and metabolic status as well as
      echocardiographic profiles and carotid artery intima-media thickness (CAIMT)
      measurements in patients with polycystic ovary syndrome (PCOS). METHODS: Forty
      two obese PCOS women aged 25-35 years, 23 women with idiopathic hirsutism and 20
      healthy controls matched for age and body mass index were enrolled.
      Anthropometric, metabolic and hormonal patterns, plasma GDF-15 concentrations,
      CAIMT, and conventional echocardiographic parameters were measured. RESULTS:
      Metabolic/lipid profiles as well as GDF-15 levels were similar across the three
      groups. CAIMT tended to be higher in PCOS group but did not reach statistical
      significance. No between-group differences were found in the conventional
      echocardiographic parameters. Analysis of PCOS patients showed a significant
      correlation of GDF-15 concentrations with age and homeostasis model assessment
      (HOMA) index (r=0.319, P<0.05, and r=0.312, P<0.05, respectively). In multiple
      linear regression analyses, GDF-15 was significantly associated with age
      (r2=0.102, P<0.05), and HOMA index (r2=0.10, P<0.05). CONCLUSION: Plasma GDF-15
      levels, CAIMT and conventional echocardiographic parameters in obese subjects
      with PCOS (25-35 yrs old) were comparable to those in either subjects with
      idiopathic hirsutism or healthy controls with similar anthropometric and
      metabolic profiles, suggesting that PCOS alone could not impart an early and
      higher risk independent of associated risk factors. GDF-15 might provide a link
      between future diabetes and cardiovascular risk in PCOS women.

PMID- 24736484
TI  - Relationship of vaspin and apelin levels with insulin resistance and
      atherosclerosis in metabolic syndrome.
AB  - AIMS: We aimed to investigate, circulating vaspin, apelin-12 and apelin-36 levels
      in subjects with metabolic syndrome (MetS) and also to search for the association
      of vaspin and apelin levels with insulin resistance (IR), high sensitivity C
      reactive protein (HsCRP), Carotid Artery Intima-Media Thickness (CIMT) and
      cardiovascular risk factors. METHODS: In this observational case-control study, a
      total of forty one patients with MetS (30 women and 11 men mean age, 41.3+/-9.4
      years) and thirty nine healthy comparison subjects (27 women and 12 men; mean
      age, 38.4+/-6.1 years) were enrolled. Serum HsCRP, lipid profile, insulin levels
      and the homeostasis model assessment of insulin resistance (HOMA-IR) were
      evaluated. Apelin-12, apelin-36 and vaspin serum levels were measured via ELISA.
      High-resolution B-mode ultrasonography was performed. RESULTS: The two study
      groups did not differ as to age, sex, blood pressure, smoking history. Vaspin,
      apelin-12 and apelin-36 levels were significantly elevated in patients with MetS
      when compared with that of control subjects (P<0.001). Serum vaspin levels showed
      a statistically significant association with CIMT (r=0.365, P<0.001) and HsCRP
      (r=0.316, P<0.01) levels, whereas both serum apelin-12 and 36 levels were
      positively correlated with HOMA-IR (r=0.344/0.462 P<0.01). CONCLUSION: Based on
      the findings of this study, Serum vaspin and apelin levels were found
      significantly higher in patients with MetS than age-matched control subjects and
      significantly associated with coronary atherosclerosis. These adipocytokines
      might play a part in the pathogenesis of MetS. Also serum Apelin levels can be
      used as specific markers for insulin sensitivity in patients with MetS.

PMID- 24736485
TI  - Body fat distribution by anthropometric and MRI-based techniques in relation to
      insulin secretion and action in men with diabetes.
AB  - AIM: Differences in fat accumulation and distribution might be responsible for
      the greater insulin resistance (IR) in type 2 diabetes. The study aims at
      examining the relationship between fat accumulation and distribution, and insulin
      secretion and action, by multilevel methodological approach. METHODS: Thirty
      three diabetic men (D), and 28 sex, age and BMI-matched controls (C) were studied
      for glucose and insulin during OGTT, insulin resistance and sensitivity,
      employing HOMA and Matsuda index respectively, and, fat accumulation and
      distribution by anthropometrics, Bioimpendance Analysis (BIA), and multiple
      slices MRI of abdomen and hip. RESULTS: D exhibited higher HOMA compared to C
      (P<0.001), and lower Matsuda index (P=0.062). No differences in fat distribution
      by anthropometric or MRI measurements were observed; however, fat accumulation by
      BIA was higher in D (P=0.035). HOMA correlated to basal, AUC, and peak insulin in
      both groups (all P<0.001); with weight (r=0.415, P=0.031), hip circumference (HC)
      (r=0.482, P=0.011), %fat (r=0.400, P<0.05) in C; and with weight, BMI, total and
      %fat, and waist and HC when all subjects were considered as a group. Matsuda
      inversely correlated with basal, AUC, and peak insulin (all P<0.001), and HC (r=
      0.406, P=0.032) in C. HOMA strongest correlated with L3-L4 subcutaneous (r=0.551,
      P=0.003) in C, and with L3-L4 visceral (r=0.456, P=0.022) in D. CONCLUSION: The
      greater IR in diabetic patients may not be interpreted by differences in fat
      distribution. IR correlates with different fat compartments in healthy and
      diabetic subjects of comparable fat distribution, suggesting differences in fat
      function.

PMID- 24736486
TI  - Association of hematological parameters with insulin resistance in type 1
      diabetes.
AB  - AIM: Previous studies reported independent associations of hematological
      parameters with insulin resistance. The aim of this study was to explore the
      associations of hematological parameters, including red blood cell count (RBC),
      hemoglobin (Hgb), white blood cell count (WBC), and platelets with insulin
      resistance in type 1 diabetes. METHODS: Study included 353 patients with type 1
      diabetes. None showed signs of acute or chronic inflammatory, renal and
      cardiovascular diseases. Insulin sensitivity was measured with estimated glucose
      disposal rate (eGDR) calculated with the equation: eGDR=24.31-(12.22xWHR)
      (3.29xAHT)-(0.57xHbA1c). The units were mg.kg-1min-1; WHR=waist to hip ratio;
      AHT=hypertension. RESULTS: RBC, Hgb, and WBC significantly correlated with
      insulin resistance measured by eGDR (r=-0.12, -0.21, and -0.14, respectively, all
      P<=0.01), and its components disorders, most notably WHR (r=0.38, 0.44, and 0.16,
      respectively, all P<=0.001). In a multiple logistic regression analysis after
      adjustment for age, sex, duration of diabetes and BMI, the presence of insulin
      resistance was independently associated with WBC count (odds ratio=1.28, P<0.01).
      The risk of insulin resistance increases by a factor of 4.41 for those in the 4th
      quartile of WBC, compared to those in 1st quartile. CONCLUSION: The significant
      independent association of WBC with the presence of insulin resistance suggests a
      role of subclinical inflammation in its pathogenesis.

PMID- 24736487
TI  - A1c, glucose variability and hypoglycemia risk in patients with type 1 diabetes.
AB  - AIM: The aim of this paper was to compare the predictive value of glycated
      hemoglobin (A1c) and glucose variability (GV) in the risk of hypoglycemia in
      patients with type 1 diabetes (T1D). METHODS: Analysis of continuous glucose
      monitoring performed in 130 T1D patients with a diabetes background of 17.1+/-8.6
      years, in intensive insulin therapy (49.8+/-17.9 UI per day). Mean interstitial
      glucose (in mg/dL), GV (standard deviation of mean glucose, in mg/dL), time per
      day spent in hypoglycemia (interstitial glucose <=70 mg/dL, in %), and episodes
      of asymptomatic or nocturnal hypoglycemia, (hypoglycemia between midnight and 8
      a.m., in %), were assessed. Patients were divided into two groups: group I
      (N.=84) with A1C<=7.5% and group II (N.=46) with A1C>7.5%. A statistical analysis
      was performed using SPSS, version 21.0(r). RESULTS: Group I presented a
      significantly lower mean glucose (139.2+/-25.9 vs. 173.1+/-33.2 mg/dL, P<0.05)
      and GV (58.4+/-18.8 vs. 70.3+/-18.6 mg/dL, P<0.05) and more hypoglycemia time
      (7.65+/-7.04 vs. 5.35+/-5.64%, P<0.05). The number of patients with nocturnal
      hypoglycemia was not significantly different in both groups (8.7 vs. 5.8%,
      P>0.05). Hypoglycemia time was positively correlated with GV (r=0.23, P=0.01) and
      negatively with A1C and mean glucose (r=-0.23 and r=-0.36; P=0.01). In
      multivariate analysis, GV and mean glucose were associated with hypoglycemia time
      (beta=0.22 and beta=-0.15, P<0.01, respectively), independent of A1c, diabetes
      duration and insulin dose; nocturnal hypoglycemia was only associated with mean
      glucose (OR=0.9, P<0.05) and was associated with a 16-fold increased risk of
      asymptomatic hypoglycemia (OR: 16.9, P<0.01). CONCLUSION: Patients with high
      HbA1c still remain at risk of hypoglycemia. Glucose variability independently
      predicts daily time spent in hypoglycemia. At night, hypoglycemia only correlates
      with mean glucose, suggesting that daily fluctuations are probably due to
      inadequate meals insulin coverage. The potential of GV for predicting
      hypoglycemia time supports the inclusion of measures of GV into a global diabetes
      strategy.

PMID- 24736488
TI  - Epicardial adipose tissue in patients with subclinical hypothyroidism.
AB  - AIM: There remains conflicting opinions regarding the relationship between the
      risk of cardiovascular disease and subclinical hypothyroidism (SH), and there are
      also varying study results. Recent growing evidence suggests that epicardial
      adipose tissue (EAT) may play a key role in the pathogenesis and development of
      coronary artery disease. The effects of SH on echocardiographic EAT is not
      currently known. The aim of this present study was to measure echocardiographic
      EAT with anthropometric and clinical parameters in patients with SH. METHODS: The
      study was designed as a prospective and case-controlled study. Body fat ratio,
      echocardiographic EAT measurements, body mass index, and the waist circumference
      of patients were measured for analysis. RESULTS: Epicardial adipose tissue was
      measured to be 3.83+/-1.04 mm for patients with SH, while it was measured to be
      2.81+/-0.74 mm in the control group, and there was a significant difference
      detected between two groups (P<0.001). CONCLUSION: In the present study
      significantly increased EAT in patients with SH was detected.

PMID- 24736490
TI  - Female sexual function of overweight women with gestational diabetes mellitus - a
      cross-sectional study.
AB  - Obesity and gestational diabetes mellitus (GDM) are increasing worldwide and may
      compromise female sexual function. We hypothesize that among GDM patients in the
      third trimester of pregnancy, those with excess body fat would have worse female
      sexual function scores than normal weight women. Our aim was to assess the sexual
      function of overweight compared to normal weight women with GDM. This was a cross
      sectional survey involving 143 Brazilian women with GDM in the third trimester of
      pregnancy: 76 were overweight (pre-pregnancy body mass index-BMI>=25.0 Kg/m2) and
      67 were normal weight (BMI 18.5-24.9 Kg/m2). Participants were recruited from
      March 2010 to April 2013 at the antenatal clinic of a single public tertiary
      teaching institution. The Female Sexual Function Index (FSFI) questionnaire was
      used to assess sexual function. Overall, 51.7% of the 143 participants were at
      risk for sexual dysfunction symptoms (FSFI scores <=26); this rate was
      significantly higher among overweight compared to normal weight women (60.5%
      versus 41.8%, p = 0.038). Mean total FSFI scores were significantly lower in
      overweight compared to normal weight women (21.7+/-9.2 versus 24.9+/-8.0, p =
      0.029). Compared to normal weight women, overweight participants had lower mean
      scores in desire (3.4+/-1.2 versus 4.0+/-1.4, p = 0.007) and lubrication (3.8+/
      2.0 versus 4.5+/-1.6, p = 0.023). According to these results, overweight women
      with GDM in the third trimester of pregnancy have lower female sexual function
      scores than normal weight women with the same disorder. 

PMID- 24736489
TI  - The role of SOG1, a plant-specific transcriptional regulator, in the DNA damage
      response.
AB  - Plants are inescapably exposed to environmental stress because of their sessile
      lifestyle. Such stress induces the production of reactive oxygen species (ROS),
      which are in turn a source of genotoxic stress. ROS are also generated
      intrinsically during photosynthesis in the chloroplasts. Furthermore, plants are
      affected by the UV component of sunlight, which damages their genomes. To protect
      their genomic integrity from DNA damage, plants activate a DNA damage response
      (DDR) system that regulates cell cycle arrest, DNA repair, and programmed cell
      death. Although plants have orthologs of several of the DDR factors that are
      found in animals, certain critical animal DDR factors, notably the tumor
      suppressor p53 and the DDR kinases CHK1 and CHK2, have not been found in plants.
      In this mini-review, we summarize the functions and regulatory mechanism of
      Arabidopsis thaliana SUPPRESSOR OF GAMMA RESPONSE 1 (SOG1), a plant-specific
      transcription factor that plays a central role in the DDR. The characteristics of
      SOG1 are similar to those of animal p53, even though the proteins' amino acid
      sequences are unrelated. We suggest that plants acquired the central
      transcriptional factor SOG1 as a functional homolog of p53 during the evolution
      of their DDR system. 

PMID- 24736491
TI  - Emotional context influences micro-expression recognition.
AB  - Micro-expressions are often embedded in a flow of expressions including both
      neutral and other facial expressions. However, it remains unclear whether the
      types of facial expressions appearing before and after the micro-expression,
      i.e., the emotional context, influence micro-expression recognition. To address
      this question, the present study used a modified METT (Micro-Expression Training
      Tool) paradigm that required participants to recognize the target micro
      expressions presented briefly between two identical emotional faces. The results
      of Experiments 1 and 2 showed that negative context impaired the recognition of
      micro-expressions regardless of the duration of the target micro-expression.
      Stimulus-difference between the context and target micro-expression was accounted
      for in Experiment 3. Results showed that a context effect on micro-expression
      recognition persists even when the stimulus similarity between the context and
      target micro-expressions was controlled. Therefore, our results not only provided
      evidence for the context effect on micro-expression recognition but also
      suggested that the context effect might result from both the stimulus and valence
      differences. 

PMID- 24736492
TI  - Air pollution is worse in London than in north of England, Public Health England
      says.

PMID- 24736493
TI  - A special issue on sports vision.

PMID- 24736494
TI  - The relationship of vision and skilled movement-a general review using cricket
      batting.
AB  - Skilled movement is not a spontaneous muscular response but represents the final
      step in a sequence of complicated processes within the central nervous system. An
      athlete absorbs information from the surrounding sporting environment and
      processes this information. The final output produces a movement response. The
      first type of visual information processing involves the reception of visual
      information that is affected by the ocular characteristics of the athlete's
      visual system (hardware). The second type of visual information processing
      involves the perception of visual information that is influenced by the
      strategies an athlete develops through experience, which results in processing
      the incoming information more efficiently (software). Drawing from the scientific
      literature, this presentation will use the sport of cricket to identify and
      explain the complex relationship between "hardware" and "software." 

PMID- 24736496
TI  - Determining the polarization state of an extreme ultraviolet free-electron laser
      beam using atomic circular dichroism.
AB  - Ultrafast extreme ultraviolet and X-ray free-electron lasers are set to
      revolutionize many domains such as bio-photonics and materials science, in a
      manner similar to optical lasers over the past two decades. Although their number
      will grow steadily over the coming decade, their complete characterization
      remains an elusive goal. This represents a significant barrier to their wider
      adoption and hence to the full realization of their potential in modern photon
      sciences. Although a great deal of progress has been made on temporal
      characterization and wavefront measurements at ultrahigh extreme ultraviolet and
      X-ray intensities, only few, if any progress on accurately measuring other key
      parameters such as the state of polarization has emerged. Here we show that by
      combining ultra-short extreme ultraviolet free electron laser pulses from FERMI
      with near-infrared laser pulses, we can accurately measure the polarization state
      of a free electron laser beam in an elegant, non-invasive and straightforward
      manner using circular dichroism. 

PMID- 24736495
TI  - Myo/Nog cells: targets for preventing the accumulation of skeletal muscle-like
      cells in the human lens.
AB  - Posterior capsule opacification (PCO) is a vision impairing condition that arises
      in some patients following cataract surgery. The fibrotic form of PCO is caused
      by myofibroblasts that may emerge in the lens years after surgery. In the chick
      embryo lens, myofibroblasts are derived from Myo/Nog cells that are identified by
      their expression of the skeletal muscle specific transcription factor MyoD, the
      bone morphogenetic protein inhibitor Noggin, and the epitope recognized by the G8
      monoclonal antibody. The goal of this study was to test the hypothesis that
      depletion of Myo/Nog cells will prevent the accumulation of myofibroblasts in
      human lens tissue. Myo/Nog cells were present in anterior, equatorial and bow
      regions of the human lens, cornea and ciliary processes. In anterior lens tissue
      removed by capsulorhexis, Myo/Nog cells had synthesized myofibroblast and
      skeletal muscle proteins, including vimentin, MyoD and sarcomeric myosin. Alpha
      smooth muscle actin (alpha-SMA) was detected in a subpopulation of Myo/Nog cells.
      Areas of the capsule denuded of epithelial cells were surrounded by Myo/Nog
      cells. Some of these cell free areas contained a wrinkle in the capsule.
      Depletion of Myo/Nog cells eliminated cells expressing skeletal muscle proteins
      in 5-day cultures but did not affect cells immunoreactive for beaded filament
      proteins that accumulate in differentiating lens epithelial cells. Transforming
      growth factor-betas 1 and 2 that mediate an epithelial-mesenchymal transition,
      did not induce the expression of skeletal muscle proteins in lens cells following
      Myo/Nog cell depletion. This study demonstrates that Myo/Nog cells in anterior
      lens tissue removed from cataract patients have undergone a partial
      differentiation to skeletal muscle. Myo/Nog cells appear to be the source of
      skeletal muscle-like cells in explants of human lens tissue. Targeting Myo/Nog
      cells with the G8 antibody during cataract surgery may reduce the incidence of
      PCO.

PMID- 24736497
TI  - Modelling Interactions between forest pest invasions and human decisions
      regarding firewood transport restrictions.
AB  - The invasion of nonnative, wood-boring insects such as the Asian longhorned
      beetle (A. glabripennis) and the emerald ash borer (A. planipennis) is a serious
      ecological and economic threat to Canadian deciduous and mixed-wood forests.
      Humans act as a major vector for the spread of these pests via firewood
      transport, although existing models do not explicitly capture human decision
      making regarding firewood transport. In this paper we present a two-patch coupled
      human-environment system model that includes social influence and long-distance
      firewood transport and examines potential strategies for mitigating pest spread.
      We found that increasing concern regarding infestations (f) significantly reduced
      infestation. Additionally it resulted in multiple thresholds at which the
      intensity of infestation in a patch was decreased. It was also found that a
      decrease in the cost of firewood purchased in the area where it is supposed to be
      burned (Cl) resulted in an increased proportion of local-firewood strategists,
      and a 67% decrease in Cl from $6.75 to $4.50 was sufficient to eliminate
      crosspatch infestation. These effects are synergistic: increasing concern through
      awareness and education campaigns acts together with reduced firewood costs,
      thereby reducing the required threshold of both awareness and economic
      incentives. Our results indicate that the best management strategy includes a
      combination of public education paired with firewood subsidization. 

PMID- 24736498
TI  - The KIT gene is associated with the english spotting coat color locus and
      congenital megacolon in Checkered Giant rabbits (Oryctolagus cuniculus).
AB  - The English spotting coat color locus in rabbits, also known as Dominant white
      spotting locus, is determined by an incompletely dominant allele (En). Rabbits
      homozygous for the recessive wild-type allele (en/en) are self-colored,
      heterozygous En/en rabbits are normally spotted, and homozygous En/En animals are
      almost completely white. Compared to vital en/en and En/en rabbits, En/En animals
      are subvital because of a dilated ("mega") cecum and ascending colon. In this
      study, we investigated the role of the KIT gene as a candidate for the English
      spotting locus in Checkered Giant rabbits and characterized the abnormalities
      affecting enteric neurons and c-kit positive interstitial cells of Cajal (ICC) in
      the megacolon of En/En rabbits. Twenty-one litters were obtained by crossing
      three Checkered Giant bucks (En/en) with nine Checkered Giant (En/en) and two
      en/en does, producing a total of 138 F1 and backcrossed rabbits. Resequencing all
      coding exons and portions of non-coding regions of the KIT gene in 28 rabbits of
      different breeds identified 98 polymorphisms. A single nucleotide polymorphism
      genotyped in all F1 families showed complete cosegregation with the English
      spotting coat color phenotype (theta=0.00 LOD  =75.56). KIT gene expression in
      cecum and colon specimens of En/En (pathological) rabbits was 5-10% of that of
      en/en (control) rabbits. En/En rabbits showed reduced and altered c-kit
      immunolabelled ICC compared to en/en controls. Morphometric data on whole mounts
      of the ascending colon showed a significant decrease of HuC/D (P<0.05) and
      substance P (P<0.01) immunoreactive neurons in En/En vs. en/en. Electron
      microscopy analysis showed neuronal and ICC abnormalities in En/En tissues. The
      En/En rabbit model shows neuro-ICC changes reminiscent of the human non
      aganglionic megacolon. This rabbit model may provide a better understanding of
      the molecular abnormalities underlying conditions associated with non-aganglionic
      megacolon.

PMID- 24736499
TI  - Thromboxane A(2) receptor stimulation promotes closure of the rat ductus
      arteriosus through enhancing neointima formation.
AB  - Ductus arteriosus (DA) closure follows constriction and remodeling of the entire
      vessel wall. Patent ductus arteriosus occurs when the DA does not close after
      birth, and this condition is currently treated using cyclooxygenase inhibitors.
      However, the efficacy of cyclooxygenase inhibitors is often limited. Our previous
      study demonstrated that low-dose thromboxane A2 receptor (TP) stimulation
      constricted the DA with minimal adverse effects in rat neonates. However, its
      effect on DA remodeling remains unknown. In this study, we focused on the impact
      of the exogenous TP stimulation on the DA remodeling, especially intimal
      thickening. Using DA explants from rat fetuses at embryonic day 19 as a ex vivo
      model and primary cultured rat DA smooth muscle cells from embryonic day 21 as a
      in vitro model, we evaluated the effect of TP stimulation on the DA remodeling.
      The selective TP agonists U46619 and I-BOP promoted neointima formation in the ex
      vivo DA explants, and TP stimulation increased DA SMC migration in a dose
      dependent manner. Both effects were inhibited by the selective TP antagonist
      SQ29548 or the siRNA against TP. TP stimulation also increased DA SMC
      proliferation in the presence of 10% fetal bovine serum. LC/MS/MS analysis
      revealed that TP stimulation increased secretion of several extracellular matrix
      proteins that may contribute to an increase in neointima formation. In
      conclusion, we uncovered that exogenous administration of TP agonist promotes
      neointima formation through the induction of migration and proliferation of DA
      SMC, which could contribute to DA closure and also to its vasoconstrictive
      action. 

PMID- 24736500
TI  - Increasing mechanical strength of gelatin hydrogels by divalent metal ion
      removal.
AB  - The usage of gelatin hydrogel is limited due to its instability and poor
      mechanical properties, especially under physiological conditions. Divalent metal
      ions present in gelatin such as Ca(2+) and Fe(2+) play important roles in the
      gelatin molecule interactions. The objective of this study was to determine the
      impact of divalent ion removal on the stability and mechanical properties of
      gelatin gels with and without chemical crosslinking. The gelatin solution was
      purified by Chelex resin to replace divalent metal ions with sodium ions. The gel
      was then chemically crosslinked by 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide
      (EDC). Results showed that the removal of divalent metal ions significantly
      impacted the formation of the gelatin network. The purified gelatin hydrogels had
      less interactions between gelatin molecules and form larger-pore network which
      enabled EDC to penetrate and crosslink the gel more efficiently. The crosslinked
      purified gels showed small swelling ratio, higher crosslinking density and
      dramatically increased storage and loss moduli. The removal of divalent ions is a
      simple yet effective method that can significantly improve the stability and
      strength of gelatin hydrogels. The in vitro cell culture demonstrated that the
      purified gelatin maintained its ability to support cell attachment and spreading.

PMID- 24736501
TI  - Global diversification at the harsh sea-land interface: mitochondrial phylogeny
      of the supralittoral isopod genus Tylos (Tylidae, Oniscidea).
AB  - The supralittoral environment, at the transition between sea and land, is
      characterized by harsh conditions for life. Nonetheless, evolution of terrestrial
      isopods (Oniscidea), the only group of Crustacea fully adapted to live on land,
      appears to have involved a transitional step within the supralittoral. The two
      most basal oniscidean lineages (Ligiidae and Tylidae) have representatives that
      successfully colonized the supralittoral. One of them is the genus Tylos, which
      is found exclusively in supralittoral sandy beaches from tropical and subtropical
      coasts around the world. Comprehensive phylogenetic hypotheses for this genus are
      lacking, which are necessary for understanding the evolution and biogeography of
      a lineage that successfully diversified in the harsh sea-land interface. Herein,
      we studied the phylogenetic relationships among 17 of the 21 currently recognized
      species of the genus Tylos, based on sequences from four mitochondrial genes
      (Cytochrome Oxidase I, Cytochrome b, 16S rDNA, and 12S rDNA). Maximum Likelihood
      and Bayesian phylogenetic analyses identified several lineages with deep
      divergences and discrete geographic distributions. Phylogenetic and
      distributional patterns of Tylos provide important clues on the biogeography and
      evolution of this group. Large divergences among the most basal clades are
      consistent with ancient splits. Due to the biological characteristics of Tylos,
      which likely prevent dispersal of these isopods across vast oceanic scales, we
      argue that tectonic events rather than trans-oceanic dispersal explain the
      distribution of Tylos in different continents. Overwater dispersal, however,
      likely enabled range expansions within some basins, and explains the colonization
      of volcanic oceanic islands. Present-day distributions were also likely
      influenced by sea level and climate changes. High levels of allopatric cryptic
      genetic differentiation are observed in different regions of the world, implying
      that the dispersal abilities of Tylos isopods are more limited than previously
      thought. Our results indicate that a taxonomic revision of this group is
      necessary. 

PMID- 24736502
TI  - The role of wildfire, prescribed fire, and mountain pine beetle infestations on
      the population dynamics of black-backed woodpeckers in the black hills, South
      Dakota.
AB  - Wildfire and mountain pine beetle infestations are naturally occurring
      disturbances in western North American forests. Black-backed woodpeckers
      (Picoides arcticus) are emblematic of the role these disturbances play in
      creating wildlife habitat, since they are strongly associated with recently
      killed forests. However, management practices aimed at reducing the economic
      impact of natural disturbances can result in habitat loss for this species.
      Although black-backed woodpeckers occupy habitats created by wildfire, prescribed
      fire, and mountain pine beetle infestations, the relative value of these habitats
      remains unknown. We studied habitat-specific adult and juvenile survival
      probabilities and reproductive rates between April 2008 and August 2012 in the
      Black Hills, South Dakota. We estimated habitat-specific adult and juvenile
      survival probability with Bayesian multi-state models and habitat-specific
      reproductive success with Bayesian nest survival models. We calculated asymptotic
      population growth rates from estimated demographic rates with matrix projection
      models. Adult and juvenile survival and nest success were highest in habitat
      created by summer wildfire, intermediate in MPB infestations, and lowest in
      habitat created by fall prescribed fire. Mean posterior distributions of
      population growth rates indicated growing populations in habitat created by
      summer wildfire and declining populations in fall prescribed fire and mountain
      pine beetle infestations. Our finding that population growth rates were positive
      only in habitat created by summer wildfire underscores the need to maintain early
      post-wildfire habitat across the landscape. The lower growth rates in fall
      prescribed fire and MPB infestations may be attributed to differences in predator
      communities and food resources relative to summer wildfire. 

PMID- 24736504
TI  - MicroRNA-338 inhibits growth, invasion and metastasis of gastric cancer by
      targeting NRP1 expression.
AB  - NRP1 as multifunctional non-tyrosine-kinase receptors play critical roles in
      tumor progression. MicroRNAs (miRNAs) are an important class of pervasive genes
      that are involved in a variety of biological functions, particularly cancer. It
      remains unclear whether miRNAs can regulate the expression of NRP1. The goal of
      this study was to identify miRNAs that could inhibit the growth, invasion and
      metastasis of gastric cancer by targeting NRP1 expression. We found that miR-338
      expression was reduced in gastric cancer cell lines and in gastric cancer
      tissues. Moreover, we found that miR-338 inhibited gastric cancer cell migration,
      invasion, proliferation and promoted apoptosis by targeting NRP1 expression. As
      an upstream regulator of NRP1, miR-338 directly targets NRP1. The forced
      expression of miR-338 inhibited the phosphorylation of Erk1/2, P38 MAPK and Akt;
      however, the expression of phosphorylated Erk1/2, P38 MAPK and Akt was restored
      by the overexpression of NRP1. In AGS cells infected with miR-338 or transfected
      with SiNRP1, the protein levels of fibronectin, vimentin, N-cadherin and SNAIL
      were decreased, but the expression of E-cadherin was increased. The expression of
      mesenchymal markers in miR-338-expressing cells was restored to normal levels by
      the restoration of NRP1 expression. In vivo, miR-338 also decreased tumor growth
      and suppressed D-MVA by targeting NRP1. Therefore, we conclude that miR-338 acts
      as a novel tumor suppressor gene in gastric cancer. miR-338 can decrease
      migratory, invasive, proliferative and apoptotic behaviors, as well as gastric
      cancer EMT, by attenuating the expression of NRP1. 

PMID- 24736506
TI  - Re: False-negative transcranial motor-evoked potentials during scoliosis surgery
      causing paralysis. Spine 2009; 34:e896-900.

PMID- 24736505
TI  - Variation in Arabidopsis flowering time associated with cis-regulatory variation
      in CONSTANS.
AB  - The onset of flowering, the change from vegetative to reproductive development,
      is a major life history transition in flowering plants. Recent work suggests that
      mutations in cis-regulatory mutations should play critical roles in the evolution
      of this (as well as other) important adaptive traits, but thus far there has been
      little evidence that directly links regulatory mutations to evolutionary change
      at the species level. While several genes have previously been shown to affect
      natural variation in flowering time in Arabidopsis thaliana, most either show
      protein-coding changes and/or are found at low frequency (<5%). Here we identify
      and characterize natural variation in the cis-regulatory sequence in the
      transcription factor CONSTANS that underlies flowering time diversity in
      Arabidopsis. Mutation in this regulatory motif evolved recently and has spread to
      high frequency in Arabidopsis natural accessions, suggesting a role for these cis
      regulatory changes in adaptive variation of flowering time. 

PMID- 24736508
TI  - Modi HN, Suh SW, Yang JH, et al. False-negative transcranial motor-evoked
      potentials during scoliosis surgery causing paralysis. Spine 2009;34:e896-900.

PMID- 24736511
TI  - Modi HN, Suh SW, Yang JH, et al. False-negative transcranial motor-evoked
      potentials during scoliosis surgery causing paralysis. Spine 2009;34:e896-900.

PMID- 24736512
TI  - Re: False-negative transcranial motor-evoked potentials during scoliosis surgery
      causing paralysis. Spine 2009; 34:e896-900.

PMID- 24736513
TI  - Re: False-negative transcranial motor-evoked potentials during scoliosis surgery
      causing paralysis. Spine 2009; 34:e896-900.

PMID- 24736515
TI  - Modi HN, Suh SW, Yang JH, et al. False-negative transcranial motor-evoked
      potentials during scoliosis surgery causing paralysis. Spine 2009;34:e896-900.

PMID- 24736516
TI  - Point of view.

PMID- 24736520
TI  - Changes in alexithymia following psychological intervention: a review.
AB  - Alexithymia, a deficit characterized by difficulties identifying,
      differentiating, and articulating emotions, is associated with significant
      physical and mental health impairment. It is generally accepted that alexithymia
      has a negative impact on a variety of physical and mental health treatments. Less
      clear is the extent to which alexithymia itself can be modified. In this article
      we review studies that have examined the effects of psychological interventions
      on alexithymia. Taken together, findings from investigations included in this
      review suggest that alexithymia is partly modifiable with therapeutic
      interventions. Studies that directly targeted alexithymic symptoms tended to
      report significant reductions in alexithymia scores following treatment, whereas
      studies that measured changes in alexithymia but did not employ any psychological
      interventions specifically intended to treat alexithymia had more inconsistent
      results. We close by considering the practical implications of the findings, and
      by offering suggestions for future research. 

PMID- 24736521
TI  - Alternative national guidelines for treating attention and depression problems in
      children: comparison of treatment approaches and prescribing rates in the United
      Kingdom and United States.
AB  - The use of psychotropic medications for children and adolescents with attention
      and depression problems continues to generate both attention in the news media
      and controversy within the field. Given that the United Kingdom has recently
      issued guidelines for its national health service that differ substantially from
      those in the United States, the time is ripe to reexamine the evidence. The
      purpose of this article is to describe the UK's new "stepped care" guidelines for
      treating attention and depression problems in children and to compare them to the
      US guidelines issued by the American Academy of Pediatrics and the American
      Academy of Child and Adolescent Psychiatry. Our findings are that, despite many
      similarities, the UK guidelines are generally more conservative in their
      recommendations for medication use, especially for children experiencing only
      moderate impairment. Our article also compares prescription and diagnosis rates
      in the UK and the US, and reports evidence for lower rates of prescribing in the
      UK, despite some evidence that the rates of problems may not differ
      substantially. We conclude by noting that the existence of an alternative
      standard provides validation for clinicians or families who prefer to take a more
      conservative approach to medication use. The two different approaches to care
      also provide a valuable opportunity for research to determine whether the
      approaches result in different treatment outcomes. 

PMID- 24736523
TI  - FR-CAPTCHA: CAPTCHA based on recognizing human faces.
AB  - A Completely Automated Public Turing test to tell Computers and Humans Apart
      (CAPTCHA) is designed to distinguish humans from machines. Most of the existing
      tests require reading distorted text embedded in a background image. However,
      many existing CAPTCHAs are either too difficult for humans due to excessive
      distortions or are trivial for automated algorithms to solve. These CAPTCHAs also
      suffer from inherent language as well as alphabet dependencies and are not
      equally convenient for people of different demographics. Therefore, there is a
      need to devise other Turing tests which can mitigate these challenges. One such
      test is matching two faces to establish if they belong to the same individual or
      not. Utilizing face recognition as the Turing test, we propose FR-CAPTCHA based
      on finding matching pairs of human faces in an image. We observe that, compared
      to existing implementations, FR-CAPTCHA achieves a human accuracy of 94% and is
      robust against automated attacks. 

PMID- 24736522
TI  - Investigating the toxicity, uptake, nanoparticle formation and genetic response
      of plants to gold.
AB  - We have studied the physiological and genetic responses of Arabidopsis thaliana
      L. (Arabidopsis) to gold. The root lengths of Arabidopsis seedlings grown on
      nutrient agar plates containing 100 mg/L gold were reduced by 75%. Oxidized gold
      was subsequently found in roots and shoots of these plants, but gold
      nanoparticles (reduced gold) were only observed in the root tissues. We used a
      microarray-based study to monitor the expression of candidate genes involved in
      metal uptake and transport in Arabidopsis upon gold exposure. There was up
      regulation of genes involved in plant stress response such as glutathione
      transferases, cytochromes P450, glucosyl transferases and peroxidases. In
      parallel, our data show the significant down-regulation of a discreet number of
      genes encoding proteins involved in the transport of copper, cadmium, iron and
      nickel ions, along with aquaporins, which bind to gold. We used Medicago sativa
      L. (alfalfa) to study nanoparticle uptake from hydroponic culture using ionic
      gold as a non-nanoparticle control and concluded that nanoparticles between 5 and
      100 nm in diameter are not directly accumulated by plants. Gold nanoparticles
      were only observed in plants exposed to ionic gold in solution. Together, we
      believe our results imply that gold is taken up by the plant predominantly as an
      ionic form, and that plants respond to gold exposure by up-regulating genes for
      plant stress and down-regulating specific metal transporters to reduce gold
      uptake. 

PMID- 24736524
TI  - More patients are waiting for hospital treatment, and for longer.

PMID- 24736525
TI  - Testes mass, but not sperm length, increases with higher levels of polyandry in
      an ancient sex model.
AB  - There is strong evidence that polyandrous taxa have evolved relatively larger
      testes than monogamous relatives. Sperm size may either increase or decrease
      across species with the risk or intensity of sperm competition. Scorpions
      represent an ancient direct mode with spermatophore-mediated sperm transfer and
      are particularly well suited for studies in sperm competition. This work aims to
      analyze for the first time the variables affecting testes mass, ejaculate volume
      and sperm length, according with their levels of polyandry, in species belonging
      to the Neotropical family Bothriuridae. Variables influencing testes mass and
      sperm length were obtained by model selection analysis using corrected Akaike
      Information Criterion. Testes mass varied greatly among the seven species
      analyzed, ranging from 1.6 +/- 1.1 mg in Timogenes dorbignyi to 16.3 +/- 4.5 mg
      in Brachistosternus pentheri with an average of 8.4 +/- 5.0 mg in all the
      species. The relationship between testes mass and body mass was not significant.
      Body allocation in testes mass, taken as Gonadosomatic Index, was high in
      Bothriurus cordubensis and Brachistosternus ferrugineus and low in Timogenes
      species. The best-fitting model for testes mass considered only polyandry as
      predictor with a positive influence. Model selection showed that body mass
      influenced sperm length negatively but after correcting for body mass, none of
      the variables analyzed explained sperm length. Both body mass and testes mass
      influenced spermatophore volume positively. There was a strong phylogenetic
      effect on the model containing testes mass. As predicted by the sperm competition
      theory and according to what happens in other arthropods, testes mass increased
      in species with higher levels of sperm competition, and influenced positively
      spermatophore volume, but data was not conclusive for sperm length.

PMID- 24736526
TI  - Post-surgical analgesia in rainbow trout: is reduced cardioventilatory activity a
      sign of improved animal welfare or the adverse effects of an opioid drug?
AB  - The use of fish models in biomedical research is increasing. Since behavioural
      and physiological consequences of surgical procedures may affect experimental
      results, these effects should be defined and, if possible, ameliorated. Thus, the
      use of post-surgical analgesia should be considered after invasive procedures
      also in fish, but presently, little information exists on the effects of
      analgesics in fish. This study assessed the effects of an opioid drug,
      buprenorphine (0.05 mg/kg IM), on resting ventilation and heart rates during 7
      days of postsurgical recovery in rainbow trout (Oncorhynchus mykiss) at 10
      degrees C by non-invasively recording bioelectric potentials from the fish via
      electrodes in the water. Baseline ventilation and heart rates were considerably
      lower compared to previously reported values for rainbow trout at 10 degrees C,
      possibly due to the non-invasive recording technique. Buprenorphine significantly
      decreased both ventilation and heart rates further, and the effects were most
      pronounced at 4-7 days after anaesthesia, surgical procedures and administration
      of the drug. Somewhat surprisingly, the same effects of buprenorphine were seen
      in the two control groups that had not been subject to surgery. These results
      indicate that the reductions in ventilation and heart rates are not caused by an
      analgesic effect of the drug, but may instead reflect a general sedative effect
      acting on both behaviour as well as e.g. central control of ventilation in
      fishes. This resembles what has previously been demonstrated in mammals, although
      the duration of the drug effect is considerably longer in this ectothermic
      animal. Thus, before using buprenorphine for postoperative analgesic treatment in
      fish, these potentially adverse effects need further characterisation.

PMID- 24736527
TI  - The clustering of CpG islands may constitute an important determinant of the 3D
      organization of interphase chromosomes.
AB  - We used the 4C-Seq technique to characterize the genome-wide patterns of spatial
      contacts of several CpG islands located on chromosome 14 in cultured chicken
      lymphoid and erythroid cells. We observed a clear tendency for the spatial
      clustering of CpG islands present on the same and different chromosomes,
      regardless of the presence or absence of promoters within these CpG islands.
      Accordingly, we observed preferential spatial contacts between Sp1 binding motifs
      and other GC-rich genomic elements, including the DNA sequence motifs capable of
      forming G-quadruplexes. However, an anchor placed in a gene/CpG island-poor area
      formed spatial contacts with other gene/CpG island-poor areas on chromosome 14
      and other chromosomes. These results corroborate the two-compartment model of the
      spatial organization of interphase chromosomes and suggest that the clustering of
      CpG islands constitutes an important determinant of the 3D organization of the
      eukaryotic genome in the cell nucleus. Using the ChIP-Seq technique, we mapped
      the genome-wide CTCF deposition sites in the chicken lymphoid and erythroid cells
      that were used for the 4C analysis. We observed a good correlation between the
      density of CTCF deposition sites and the level of 4C signals for the anchors
      located in CpG islands but not for an anchor located in a gene desert. It is thus
      possible that CTCF contributes to the clustering of CpG islands observed in our
      experiments. 

PMID- 24736528
TI  - Plasma sphingolipids as potential indicators of hepatic necroinflammation in
      patients with chronic hepatitis C and normal alanine aminotransferase level.
AB  - Accurate estimation of hepatic necroinflammation caused by chronic hepatitis C
      (CHC) is crucial for prediction of prognosis and design of therapeutic strategy,
      which is particularly true for CHC patients with normal alanine aminotransferase
      (ALT) level. Recent studies have shown that sphingolipids have a close
      relationship with hepatitis C virus infection. The present study aimed to
      identify plasma sphingolipids related to hepatic necroinflammation. We included
      120 treatment-naive CHC patients and 64/120 had normal ALT levels (<40 U/L). CHC
      patients who underwent liver biopsies were subjected to Scheuer scoring analysis
      for scope of hepatic inflammation. Plasma sphingolipids were detected by high
      performance liquid chromatography tandem mass spectrometry. Our results showed 44
      plasma sphingolipids were detected altogether. Of all detected sphingolipids,
      hexosylceramide (HexCer) (d18?1/22?0) and HexCer (d18?1/24?0) showed a
      significant difference among G0/G1, G2, and G3/G4 (P<0.05). For identifying
      hepatic necroinflammation (G>=2), after adjusting other factors, the odds ratio
      (OR) of HexCer (d18?1/22?0) reached 1.01 (95% confidence interval [CI]: 1.00
      1.02). Furthermore, the area under the curve (AUC) of HexCer (d18?1/22?0) was 0.7
      (P = 0.01) and approached that of ALT (AUC = 0.78). However, in CHC patients with
      normal ALT, HexCer (d18?1/22?0) was an independent factor (OR: 1.02, 95% CI: 1.01
      1.03) to identify the hepatic necroinflammation (G>=2). HexCer (d18?1/22?0) not
      only showed the largest AUC (0.78, P = 0.001), but also exhibited the highest
      specificity of all indicators. These results indicate that plasma HexCer
      (d18?1/22?0) is a potential indicator to distinguish hepatic necroinflammation in
      CHC patients. For CHC with normal ALT, the ability of HexCer (d18?1/22?0) to
      distinguish hepatic necroinflammation might be superior to conventional serum
      indicators. 

PMID- 24736529
TI  - Delimiting the origin of a B chromosome by FISH mapping, chromosome painting and
      DNA sequence analysis in Astyanax paranae (Teleostei, Characiformes).
AB  - Supernumerary (B) chromosomes have been shown to contain a wide variety of
      repetitive sequences. For this reason, fluorescent in situ hybridisation (FISH)
      is a useful tool for ascertaining the origin of these genomic elements,
      especially when combined with painting from microdissected B chromosomes. In
      order to investigate the origin of B chromosomes in the fish species Astyanax
      paranae, these two approaches were used along with PCR amplification of specific
      DNA sequences obtained from the B chromosomes and its comparison with those
      residing in the A chromosomes. Remarkably, chromosome painting with the one-arm
      metacentric B chromosome probe showed hybridization signals on entire B
      chromosome, while FISH mapping revealed the presence of H1 histone and 18S rDNA
      genes symmetrically placed in both arms of the B chromosome. These results
      support the hypothesis that the B chromosome of A. paranae is an isochromosome.
      Additionally, the chromosome pairs Nos. 2 or 23 are considered the possible B
      chromosome ancestors since both contain syntenic H1 and 18S rRNA sequences. The
      analysis of DNA sequence fragments of the histone and rRNA genes obtained from
      the microdissected B chromosomes showed high similarity with those obtained from
      0B individuals, which supports the intraspecific origin of B chromosomes in A.
      paranae. Finally, the population hereby analysed showed a female-biased B
      chromosome presence suggesting that B chromosomes in this species could influence
      sex determinism. 

PMID- 24736530
TI  - Intratumoral morphological heterogeneity of breast cancer: neoadjuvant
      chemotherapy efficiency and multidrug resistance gene expression.
AB  - In this study, the influence of intratumoral morphological heterogeneity of
      breast cancer on neoadjuvant chemotherapy (NAC) efficiency was investigated. In
      particular, we analysed the association of NAC response and pre- and post-NAC
      expression of the main multidrug resistance (MDR) genes--ABCB1, ABCC1, ABCC5,
      ABCG1, and ABCG2, with the presence of different morphological structures in
      breast tumors. In addition, the expression of MDR genes was investigated in
      different morphological structures and in their microenvironment by comparing
      probes obtained using laser microdissection. The results of this study showed
      that tumors with alveolar structures were more frequently NAC-nonresponsive than
      cases without this structural type (p = 0.0028, Bonferroni-corrected p = 0.014).
      The presence of trabecular structures in breast tumors was also associated with
      chemoresistance (p = 0.0272, Bonferroni-corrected p = 0.136). High expression of
      MDR genes was not found in alveolar structures (including their microenvironment)
      and in tumors containing this structural type. In contrast, more active MDR genes
      and expression of the ABCB1 gene were found only in trabecular structures. Taken
      together, our data indicate that breast tumors with alveolar structures possess
      resistance to NAC, which is not related to high expression of MDR genes, whereas
      chemoresistance of tumors with trabecular structures can depend on the expression
      level of ABCB1.

PMID- 24736532
TI  - [The combined endoscopic hemostasis in case of gastroduodenal ulcerative
      bleeding].
AB  - It was done the retrospective analysis of the endoscopic hemostasis effectiveness
      in 207 patients with gastroduodenal bleeding in the period from November 2011 to
      April 2013. The differential approach to the choice of hemostasis methods and
      consistency of their application were developed. It was done the comparative
      analysis of two- and three-stages combined hemostasis results. The analysis
      included the infiltration of the submucosal layer by 0.01% solution of
      adrenaline, argon-plasma coagulation and hemostatic glue applique. 

PMID- 24736531
TI  - A relationship between reduced nucleus accumbens shell and enhanced lateral
      hypothalamic orexin neuronal activation in long-term fructose bingeing behavior.
AB  - Fructose accounts for 10% of daily calories in the American diet. Fructose, but
      not glucose, given intracerebroventricularly stimulates homeostatic feeding
      mechanisms within the hypothalamus; however, little is known about how fructose
      affects hedonic feeding centers. Repeated ingestion of sucrose, a disaccharide of
      fructose and glucose, increases neuronal activity in hedonic centers, the nucleus
      accumbens (NAc) shell and core, but not the hypothalamus. Rats given glucose in
      the intermittent access model (IAM) display signatures of hedonic feeding
      including bingeing and altered DA receptor (R) numbers within the NAc. Here we
      examined whether substituting fructose for glucose in this IAM produces bingeing
      behavior, alters DA Rs and activates hedonic and homeostatic feeding centers.
      Following long-term (21-day) exposure to the IAM, rats given 8-12% fructose
      solutions displayed fructose bingeing but unaltered DA D1R or D2R number.
      Fructose bingeing rats, as compared to chow bingeing controls, exhibited reduced
      NAc shell neuron activation, as determined by c-Fos-immunoreactivity (Fos-IR).
      This activation was negatively correlated with orexin (Orx) neuron activation in
      the lateral hypothalamus/perifornical area (LH/PeF), a brain region linking
      homeostatic to hedonic feeding centers. Following short-term (2-day) access to
      the IAM, rats exhibited bingeing but unchanged Fos-IR, suggesting only long-term
      fructose bingeing increases Orx release. In long-term fructose bingeing rats,
      pretreatment with the Ox1R antagonist SB-334867 (30 mg/kg; i.p.) equally reduced
      fructose bingeing and chow intake, resulting in a 50% reduction in calories.
      Similarly, in control rats, SB-334867 reduced chow/caloric intake by 60%. Thus,
      in the IAM, Ox1Rs appear to regulate feeding based on caloric content rather than
      palatability. Overall, our results, in combination with the literature, suggest
      individual monosaccharides activate distinct neuronal circuits to promote feeding
      behavior. Specifically, long-term fructose bingeing activates a hyperphagic
      circuit composed in part of NAc shell and LH/PeF Orx neurons. 

PMID- 24736533
TI  - [Diagnosis of neuroendocrine neoplasms of the pancreas].
AB  - The rare clinical case of multiple primary gastrointestinal stromal tumors (GIST)
      in one patient is presented in the article. The analysis of the available
      material confirmed that there is the problem of early detection of this type of
      tumors and their differential diagnosis. The minutes of outpatient radiological
      methods of research should include methods of identifying GIST in various
      locations. Early diagnosis of the disease allows you to make a radical mini
      invasive intervention in the endoscopic or robotic-assisted version. This tactic
      is characterized by high efficiency in combination with the chemotherapeutic
      treatment. 

PMID- 24736534
TI  - [Laparoscopic cholecystectomy in case of acute cholecystitis].
AB  - The article describes the results of laparoscopic cholecystectomy in patients
      with acute cholecystitis. 97 patients including 13 men and 84 women aged from 20
      to 74 years were included in the study. There was not the conversion to
      laparotomy and intraoperative complications in all cases. 83 patients, which
      amounted to 85.7% of the patients, were discharged on the next day after
      operation. The last 14 patients had the variation of postoperative
      hospitalization period from 2 to 4 days. Laparoscopic cholecystectomy is a safe
      and effective procedure in patients with acute cholecystitis. 

PMID- 24736535
TI  - [The version of the Bentall-DeBono operation].
AB  - The Bentall-DeBono operation was proposed in 1968. It is the "gold standard" of
      the aneurysm treatment of the ascending aorta and aortic insufficiency
      nevertheless this technique is fraught with a number of possible postoperative
      complications. We have proposed an improved method: two short (10 mm) jaws and
      "skirt"" formed from the distal portion of the prosthesis were sewed to valved
      conduit. 19 operations were done by the proposed method in all. The control group
      included 73 patients who had operation according to the standard technique.
      Duration of extracorporeal circulation, myocardial ischemia, blood loss were the
      following: 145.4+/-54.4 and 117.4+/-40.9 min; 106.4+/-30.2 and 77.5+/-22.5 min;
      473+/-355 and 1853+/-940 ml respectively. The mortality rate was 5.2% and 10.9%
      respectively. Our experience shows the technical simplicity of the procedure and
      satisfactory postoperative results. 

PMID- 24736536
TI  - [The effectiveness of the valve bronchial occlusion in case of bronchopleural
      fistulas].
AB  - The experience of endobronchial valve "Medlung" installation in 24 patients with
      bronchopleural fistula was summarized in the article. In 18 (75%) patients the
      cause of bronchopleural fistula was purulent - destructive processes in the
      lungs, including the associated trauma in 4 (22.2%) patients, pneumonia in 14
      (77.8%) patients. In 3 (12.5%) cases the cause of the bronchopleural fistula was
      the lung tumors of different localization and in 3 (12.5%) cases - idiopathic
      pulmonary fibrosis. Reasonable use of endobronchial valve in patients with
      bronchopleural fistula provides a persistent separation of the fistula and lets
      to avoid extensive, traumatic operations. 

PMID- 24736537
TI  - [Torsion and necrosis of epiploic appendices of the large bowel].
AB  - The features of the clinical symptoms was studied, the possibility of laparoscopy
      in modern diagnosis and treatment of epiploic appendices torsion and necrosis of
      the large bowel was assessed in the article. It was done the retrospective
      analysis of the medical records of 87 patients with a diagnosis of epiploic
      appendices torsion and necrosis of the large bowel. The patients had laparoscopic
      operations in our hospital in the period from January 1995 to December 2012. The
      clinical picture, laboratory and instrumental datas in cases of epiploic
      appendices torsion and necrosis were scarce and nonspecific. An abdominal pain
      preferentially localized in the lower divisions was the main symptom (97.7%). The
      instrumental methods did not allow to diagnose the torsion and necrosis of
      epiploic appendices in the majority of cases and all these techniques were used
      for the differential diagnosis with other diseases. The assumption of the
      presence of appendices torsion and necrosis occured just in 34.5% of cases before
      the operation. Diagnosis of epiploic appendices torsion and necrosis present
      significant difficulties on prehospital and preoperative stages. The diagnostic
      laparoscopy is the method of choice in unclear situations and it allows to
      diagnose the torsion and necrosis of epiploic appendices in 96.6% of cases.
      Successful surgical treatment by using laparoscopic approach is possible in 90.8%
      of cases. 

PMID- 24736538
TI  - [Metabolic therapy with Actovegin in case of ischemic syndrome of limbs].
AB  - Actovegin was used in complex conservative and surgical treatment of lower limb
      chronic ischemia and diabetic foot syndrome in 200 patients. In 120 patients
      Actovegin was used in combination with reconstructive operations, angioplasty and
      stenting for preparation for surgery. In 80 patients Actovegin was used as
      independent method of treatment. In severe cases the medicine was injected
      intravenously 1000-2000 mg No10-15, and in mild degrees (IIA-IIB) - 400-800 mg
      intramuscularly with conversion on the tablet form in the future. Clinical
      picture, dopplerographic and microcirculatory data evidence about absolute
      safety, efficiency and comparative cheapness of the parenteral and enteral forms
      of Actovegine. 

PMID- 24736539
TI  - [The experience of treatment with medicines of botulinum toxin of type A Lantox
      of chronic anal fissure with sphincter spasm].
AB  - The original material of monitoring of 118 patients with chronic anal fissure is
      presented in the article. Patients' mean age was 48.9+-10.5 years. It was used
      injections of medicine of botulinum toxin of type A (Lantox) by its introduction
      in internal anal sphincter in all patients. There was granulating wound with
      signs of marginal epithelialization in 59.3% of cases on the 10th day after
      injection. It was detected complete epithelialization of dermis defect in 93.2%
      of cases on the 21st day, after six weeks - in 100% of cases. According to
      anorectal profilometry the index of maximal and average pressure in the anal
      canal at the level of the internal sphincter in patients at rest decreased to
      norm. Lantox introduction leads to rapid and persistent reduction of pain
      intensity. "Lantox" use in ambulatory practice permits to minimize the
      indications for surgical treatment. 

PMID- 24736540
TI  - [Continuing medical education of physicians of surgical specialties].

PMID- 24736541
TI  - [Multiple primary gastrointestinal stromal tumors of the small bowel and
      duodenum].

PMID- 24736542
TI  - [Primary lymphoma of the tibia and chronic postoperative osteomyelitis].

PMID- 24736543
TI  - Noninvasive urinary metabolomic profiling identifies diagnostic and prognostic
      markers in lung cancer.
AB  - Lung cancer remains the most common cause of cancer deaths worldwide, yet there
      is currently a lack of diagnostic noninvasive biomarkers that could guide
      treatment decisions. Small molecules (<1,500 Da) were measured in urine collected
      from 469 patients with lung cancer and 536 population controls using unbiased
      liquid chromatography/mass spectrometry. Clinical putative diagnostic and
      prognostic biomarkers were validated by quantitation and normalized to creatinine
      levels at two different time points and further confirmed in an independent
      sample set, which comprises 80 cases and 78 population controls, with similar
      demographic and clinical characteristics when compared with the training set.
      Creatine riboside (IUPAC name: 2-{2-[(2R,3R,4S,5R)-3,4-dihydroxy-5
      (hydroxymethyl)-oxolan-2-yl]-1-methylcarbamimidamido}acetic acid), a novel
      molecule identified in this study, and N-acetylneuraminic acid (NANA) were each
      significantly (P < 0.00001) elevated in non-small cell lung cancer and associated
      with worse prognosis [HR = 1.81 (P = 0.0002), and 1.54 (P = 0.025),
      respectively]. Creatine riboside was the strongest classifier of lung cancer
      status in all and stage I-II cases, important for early detection, and also
      associated with worse prognosis in stage I-II lung cancer (HR = 1.71, P = 0.048).
      All measurements were highly reproducible with intraclass correlation
      coefficients ranging from 0.82 to 0.99. Both metabolites were significantly (P <
      0.03) enriched in tumor tissue compared with adjacent nontumor tissue (N = 48),
      thus revealing their direct association with tumor metabolism. Creatine riboside
      and NANA may be robust urinary clinical metabolomic markers that are elevated in
      tumor tissue and associated with early lung cancer diagnosis and worse prognosis.

PMID- 24736545
TI  - Activation of SOX2 expression by BRD4-NUT oncogenic fusion drives neoplastic
      transformation in NUT midline carcinoma.
AB  - BRD4 is implicated in the pathogenesis of a number of different cancers. It is
      also the target of translocation t(15;19) that accounts for the highly aggressive
      NUT midline carcinoma (NMC). We discovered that t(15;19) NMC cells display the
      ability to grow into stem cell-like spheres and express an exceptionally high
      level of the stem cell marker, SOX2. The BRD4-NUT fusion oncogene resulting from
      t(15;19) translocation is required for the abnormal activation of SOX2, which
      drives the stem cell-like proliferation and cellular transformation in NMC cells.
      SOX2 knockdown phenocopies the effects of BRD4-NUT inhibition, whereas ectopic
      SOX2 expression rescues the phenotype. The BRD4-NUT-induced abnormal SOX2
      activation was observed in multiple NMC cell lines as well as in NMC primary
      tumors. We further demonstrate that BRD4-NUT oncoprotein recruits p300 to
      stimulate transcription activation and that inhibition of p300 represses SOX2
      transcription in NMC cells. These studies identify this stem cell marker as a
      novel BRD4-NUT target that supports the highly aggressive transforming activity
      of t(15;19) carcinomas. Our study provides new mechanistic insights for
      understanding how alteration of BRD4 function by BRD4-NUT oncogene leads to the
      highly malignant NMC carcinoma. Because abnormal stem cell self-renewal is
      frequently observed during tumor formation and metastasis, the aberrant stem cell
      like proliferation associated with BRD4 dysregulation observed in NMC carcinoma
      may have implications for studying the oncogenic mechanism of other BRD4
      associated tumors.

PMID- 24736544
TI  - Immune-based antitumor effects of BRAF inhibitors rely on signaling by CD40L and
      IFNgamma.
AB  - B-Raf(V600E) inhibitors have been suggested to promote tumor regression with the
      help of host immunity, but this hypothesis has not been examined directly in
      detail. In this study, we profiled immunologic changes in the tumor
      microenvironment and tumor-infiltrating lymphocytes (TIL) in a B-RafV600E/Pten
      driven murine model of melanoma after administration of the B-Raf(V600E) small
      molecule inhibitor PLX4720. In this model, we found that as tumors developed,
      they gradually acquired immunosuppressive features, including accumulation of
      regulatory T cells (Treg) and CD11b(+)/Gr-1(+) myeloid cells and loss of Th1
      effector functions on CD4(+) TILs, such as CD40L and IFNgamma expression. PLX4720
      administration promoted development of a more immune stimulatory microenvironment
      associated with a relative increase in CD40L and IFNgamma expression on
      intratumoral CD4(+) TILs and a reduced accumulation of Tregs and CD11b(+)/Gr-1(+)
      myeloid cells. Strikingly, CD40L or IFNgamma blockade compromised the ability of
      PLX4720 to inhibit melanoma growth. Supporting this result, agonistic CD40
      antibody was sufficient to evoke antitumor immunity and suppress tumor growth in
      tumor-bearing mice. Taken together, our results establish the critical role of
      immune-related changes, with key contributions for CD40L and IFNgamma signaling
      in the antitumor responses triggered in vivo by B-Raf(V600E) inhibitors.

PMID- 24736546
TI  - Low-dose prospectively electrocardiogram-gated axial dual-source CT angiography
      in patients with pulsatile bilateral bidirectional Glenn Shunt: an alternative
      noninvasive method for postoperative morphological estimation.
AB  - OBJECTIVE: To explore the clinical value of low-dose prospectively
      electrocardiogram-gated axial dual-source CT angiography (low-dose PGA scanning,
      CTA) in patients with pulsatile bilateral bidirectional Glenn shunt (bBDG) as an
      alternative noninvasive method for postoperative morphological estimation.
      METHODS: Twenty patients with pulsatile bBDG (mean age 4.2+/-1.6 years) underwent
      both low-dose PGA scanning and conventional cardiac angiography (CCA) for the
      morphological changes. The morphological evaluation included the anatomy of
      superior vena cava (SVC) and pulmonary artery (PA), the anastomotic location,
      thrombosis, aorto-pulmonary collateral circulation, pulmonary arteriovenous
      malformations, etc. Objective and subjective image quality was assessed. Bland
      Altman analysis and linear regression analyses were used to evaluate the
      correlation on measurements between CTA and CCA. Effective radiation dose of both
      modalities was calculated. RESULTS: The CT attenuation value of bilateral SVC and
      PA was higher than 300 HU. The average subjective image quality score was 4.05+/
      0.69. The morphology of bilateral SVC and PA was displayed completely and
      intuitively by CTA images. There were 24 SVC above PA and 15 SVC beside PA.
      Thrombosis was found in 1 patient. Collateral vessels were detected in 13
      patients. No pulmonary arteriovenous malformation was found in our study. A
      strong correlation (R2>0.8, P<0.001) was observed between the measurements on CTA
      images and on CCA images. Bland-Altman analysis demonstrated a systematic
      overestimation of the measurements by CTA (the mean value of bias>0).The mean
      effective dose of CTA and CCA was 0.50+/-0.17 mSv and 4.85+/-1.34 mSv
      respectively. CONCLUSION: CT angiography with a low-dose PGA scanning is an
      accurate and reliable noninvasive examination in the assessment of morphological
      changes in patients with pulsatile bBDG.

PMID- 24736548
TI  - Forensic genomics as a novel tool for identifying the causes of mass mortality
      events.
AB  - Toxic spills, hypoxia, disease outbreaks and toxin-producing algal blooms are all
      possible causes of mass mortality events, but in many cases it can be difficult
      to pinpoint the cause of death. Here we present a new approach that we name
      'forensic genomics', combining field surveys, toxin testing and genomic scans.
      Forensic genomics queries allele frequencies of surviving animals for signatures
      of agents causing mass mortality and, where genetic diversity is high, is
      uniquely suited to identify natural selection in action. As a proof of concept,
      we use this approach to investigate the causes of an invertebrate mass mortality
      event, and its genetic effects on an abalone population. Our results support that
      a harmful algal bloom producing a yessotoxin was a major causative agent to the
      event. 

PMID- 24736547
TI  - Multivalent presentation of MPL by porous silicon microparticles favors T helper
      1 polarization enhancing the anti-tumor efficacy of doxorubicin nanoliposomes.
AB  - Porous silicon (pSi) microparticles, in diverse sizes and shapes, can be
      functionalized to present pathogen-associated molecular patterns that activate
      dendritic cells. Intraperitoneal injection of MPL-adsorbed pSi microparticles, in
      contrast to free MPL, resulted in the induction of local inflammation, reflected
      in the recruitment of neutrophils, eosinophils and proinflammatory monocytes, and
      the depletion of resident macrophages and mast cells at the injection site.
      Injection of microparticle-bound MPL resulted in enhanced secretion of the T
      helper 1 associated cytokines IFN-gamma and TNF-alpha by peritoneal exudate and
      lymph node cells in response to secondary stimuli while decreasing the anti
      inflammatory cytokine IL-10. MPL-pSi microparticles independently exhibited anti
      tumor effects and enhanced tumor suppression by low dose doxorubicin
      nanoliposomes. Intravascular injection of the MPL-bound microparticles increased
      serum IL-1beta levels, which was blocked by the IL-1 receptor antagonist
      Anakinra. The microparticles also potentiated tumor infiltration by dendritic
      cells, cytotoxic T lymphocytes, and F4/80+ macrophages, however, a specific
      reduction was observed in CD204+ macrophages. 

PMID- 24736551
TI  - Abstracts of the 15th Annual International Meeting of the Institute of Human
      Virology, in partnership with the Global Virus Network and the Moscow Center for
      HIV/AIDS Treatment and Prevention. September 8-12, 2013. Moscow.

PMID- 24736553
TI  - Pigment production on L-tryptophan medium by Cryptococcus gattii and Cryptococcus
      neoformans.
AB  - In recent years strains previously grouped within Cryptococcus neoformans have
      been divided into two species C. neoformans and C. gattii, with Cryptococcus
      neoformans comprising serotypes A, D, and AD and C. gattii comprising serotypes B
      and C. Cryptococcus neoformans have also been subdivided into two varieties C.
      neoformans var. grubii, serotype A, and C. neoformans var. neoformans, serotype
      D. We analyzed the growth and pigment production characteristics of 139 strains
      of Cryptococcus spp. in L-tryptophan containing media. Nearly all strains of
      Cryptococcus, including each variety and serotype tested produced a pink water
      soluble pigment (molecular weight of 535.2 Da) from L-tryptophan. Consequently,
      the partial separation of the species was based on whether the pink pigment was
      secreted into the medium (extracellular) or retained as an intracellular pigment.
      On L-tryptophan medium C. neoformans var. grubii and serotype AD produced a pink
      extracellular pigment. In contrast, for C. gattii, the pink pigment was localized
      intracellularly and masked by heavy production of brown pigments. Pigment
      production by C. neoformans var. neoformans was variable with some strains
      producing the pink extracellular pigment and others retained the pink pigment
      intracellularly. The pink intracellular pigment produced by strains of C.
      neoformans var. neoformans was masked by production of brown pigments.
      Cryptococcus laccase mutants failed to produce pigments from L-tryptophan. This
      is the first report that the enzyme laccase is involved in tryptophan metabolism.
      Prior to this report Cryptococcus laccase produced melanin or melanin like
      pigments from heterocyclic compounds that contained ortho or para diphenols,
      diaminobenzenes and aminophenol compounds. The pigments produced from L
      tryptophan were not melanin. 

PMID- 24736556
TI  - Oral biology in middle age: a history of the University at Buffalo Oral Biology
      PhD Program.
AB  - In 1960, the first Department of Oral Biology in the United States dedicated to
      the conduct of research, graduate biomedical research education, and the
      provision of basic oral science education for the DDS curriculum was established
      at the University at Buffalo. In 1963, the Department organized the first PhD
      Program in Oral Biology in the United States. This PhD program has produced a
      large cadre of oral health researchers, many of whom have gone on to make major
      contributions to dental research and education. This article provides a brief
      history of the program, the context within which the program was organized and
      developed, and a description of some of the many faculty, students, and fellows
      associated with the program. Additionally, to celebrate the 50th anniversary of
      this program, a symposium, entitled "The Oral Microbiome, Immunity and Chronic
      Disease", was held on June 12-14, 2013, in Buffalo, New York. The proceedings are
      published online in Advances in Dental Research (2014, Vol. 26). 

PMID- 24736554
TI  - miR-221/222 control luminal breast cancer tumor progression by regulating
      different targets.
AB  - alpha6beta4 integrin is an adhesion molecule for laminin receptors involved in
      tumor progression. We present a link between beta4 integrin expression and miR
      221/222 in the most prevalent human mammary tumor: luminal invasive carcinomas
      (Lum-ICs). Using human primary tumors that display different beta4 integrin
      expression and grade, we show that miR-221/222 expression inversely correlates
      with tumor proliferating index, Ki67. Interestingly, most high-grade tumors
      express beta4 integrin and low miR-221/222 levels. We ectopically transfected miR
      221/222 into a human-derived mammary tumor cell line that recapitulates the
      luminal subtype to investigate whether miR-221/222 regulates beta4 expression. We
      demonstrate that miR-221/222 overexpression results in beta4 expression
      downregulation, breast cancer cell proliferation, and invasion inhibition. The
      role of miR-221/222 in driving beta4 integrin expression is also confirmed via
      mutating the miR-221/222 seed sequence for beta4 integrin 3'UTR. Furthermore, we
      show that these 2 miRNAs are also key breast cancer cell proliferation and
      invasion regulators, via the post-transcriptional regulation of signal transducer
      and activator of transcription 5A (STAT5A) and of a disintegrin and
      metalloprotease-17 (ADAM-17). We further confirm these data by silencing ADAM-17,
      using a dominant-negative or an activated STAT5A form. miR-221/222-driven beta4
      integrin, STAT5A, and ADAM-17 did not occur in MCF-10A cells, denoted "normal"
      breast epithelial cells, indicating that the mechanism is cancer cell-specific.  
      These results provide the first evidence of a post-transcriptional mechanism that
      regulates beta4 integrin, STAT5A, and ADAM-17 expression, thus controlling breast
      cancer cell proliferation and invasion. Pre-miR-221/222 use in the aggressive
      luminal subtype may be a powerful therapeutic anti-cancer strategy. 

PMID- 24736555
TI  - Incretin treatment and risk of pancreatitis in patients with type 2 diabetes
      mellitus: systematic review and meta-analysis of randomised and non-randomised
      studies.
AB  - OBJECTIVE: To investigate the risk of pancreatitis associated with the use of
      incretin-based treatments in patients with type 2 diabetes mellitus. DESIGN:
      Systematic review and meta-analysis. DATA SOURCES: Medline, Embase, the Cochrane
      Central Register of Controlled Trials (CENTRAL), and ClinicalTrials.gov.
      ELIGIBILITY CRITERIA: Randomised and non-randomised controlled clinical trials,
      prospective or retrospective cohort studies, and case-control studies of
      treatment with glucagon-like peptide-1 (GLP-1) receptor agonists or dipeptidyl
      peptidase-4 (DPP-4) inhibitors in adults with type 2 diabetes mellitus compared
      with placebo, lifestyle modification, or active anti-diabetic drugs. DATA
      COLLECTION AND ANALYSIS: Pairs of trained reviewers independently screened for
      eligible studies, assessed risk of bias, and extracted data. A modified Cochrane
      tool for randomised controlled trials and a modified version of the Newcastle
      Ottawa scale for observational studies were used to assess bias. We pooled data
      from randomised controlled trials using Peto odds ratios, and conducted four
      prespecified subgroup analyses and a post hoc subgroup analysis. Because of
      variation in outcome measures and forms of data, we describe the results of
      observational studies without a pooled analysis. RESULTS: 60 studies (n=353,639),
      consisting of 55 randomised controlled trials (n=33,350) and five observational
      studies (three retrospective cohort studies, and two case-control studies;
      n=320,289) were included. Pooled estimates of 55 randomised controlled trials (at
      low or moderate risk of bias involving 37 pancreatitis events, raw event rate
      0.11%) did not suggest an increased risk of pancreatitis with incretins versus
      control (odds ratio 1.11, 95% confidence interval 0.57 to 2.17). Estimates by
      type of incretin suggested similar results (1.05 (0.37 to 2.94) for GLP-1
      agonists v control; 1.06 (0.46 to 2.45) for DPP-4 inhibitors v control). Analyses
      according to the type of control, mode, duration of treatment, and individual
      incretin agents suggested no differential effect by subgroups, and sensitivity
      analyses by alternative statistical modelling and effect measures did not show
      important differences in effect estimates. Three retrospective cohort studies
      (moderate to high risk of bias, involving 1466 pancreatitis events, raw event
      rate 0.47%) also did not suggest an increased risk of pancreatitis associated
      with either exenatide (adjusted odds ratios 0.93 (0.63 to 1.36) in one study and
      0.9 (0.6 to 1.5) in another) or sitagliptin (adjusted hazard ratio 1.0, 0.7 to
      1.3); a case-control study at moderate risk of bias (1003 cases, 4012 controls)
      also suggested no significant association (adjusted odds ratio 0.98, 0.69 to
      1.38). Another case-control study (1269 cases, 1269 controls) at moderate risk of
      bias, however, suggested that the use of either exenatide or sitagliptin was
      associated with significantly increased odds of acute pancreatitis (use within
      two years v no use, adjusted odds ratio 2.07, 1.36 to 3.13). CONCLUSIONS: The
      available evidence suggests that the incidence of pancreatitis among patients
      using incretins is low and that the drugs do not increase the risk of
      pancreatitis. Current evidence, however, is not definitive, and more carefully
      designed and conducted observational studies are warranted to definitively
      establish the extent, if any, of increased risk.

PMID- 24736557
TI  - Climatic warming increases winter wheat yield but reduces grain nitrogen
      concentration in east China.
AB  - Climatic warming is often predicted to reduce wheat yield and grain quality in
      China. However, direct evidence is still lacking. We conducted a three-year
      experiment with a Free Air Temperature Increase (FATI) facility to examine the
      responses of winter wheat growth and plant N accumulation to a moderate
      temperature increase of 1.5 degrees C predicted to prevail by 2050 in East China.
      Three warming treatments (AW: all-day warming; DW: daytime warming; NW: nighttime
      warming) were applied for an entire growth period. Consistent warming effects on
      wheat plant were recorded across the experimental years. An increase of ca. 1.5
      degrees C in daily, daytime and nighttime mean temperatures shortened the length
      of pre-anthesis period averagely by 12.7, 8.3 and 10.7 d (P<0.05), respectively,
      but had no significant impact on the length of the post-anthesis period. Warming
      did not significantly alter the aboveground biomass production, but the grain
      yield was 16.3, 18.1 and 19.6% (P<0.05) higher in the AW, DW and NW plots than
      the non-warmed plot, respectively. Warming also significantly increased plant N
      uptake and total biomass N accumulation. However, warming significantly reduced
      grain N concentrations while increased N concentrations in the leaves and stems.
      Together, our results demonstrate differential impacts of warming on the
      depositions of grain starch and protein, highlighting the needs to further
      understand the mechanisms that underlie warming impacts on plant C and N
      metabolism in wheat. 

PMID- 24736559
TI  - Targeted research to improve invasive species management: yellow crazy ant
      Anoplolepis gracilipes in Samoa.
AB  - Lack of biological knowledge of invasive species is recognised as a major factor
      contributing to eradication failure. Management needs to be informed by a site
      specific understanding of the invasion system. Here, we describe targeted
      research designed to inform the potential eradication of the invasive yellow
      crazy ant Anoplolepis gracilipes on Nu'utele island, Samoa. First, we assessed
      the ant's impacts on invertebrate biodiversity by comparing invertebrate
      communities between infested and uninfested sites. Second, we investigated the
      timing of production of sexuals and seasonal variation of worker abundance and
      nest density. Third, we investigated whether an association existed between A.
      gracilipes and carbohydrate sources. Within the infested area there were few
      other ants larger than A. gracilipes, as well as fewer spiders and crabs,
      indicating that A. gracilipes is indeed a significant conservation concern. The
      timing of male reproduction appears to be consistent with places elsewhere in the
      world, but queen reproduction was outside of the known reproductive period for
      this species in the region, indicating that the timing of treatment regimes used
      elsewhere are not appropriate for Samoa. Worker abundance and nest density were
      among the highest recorded in the world, being greater in May than in October.
      These abundance and nest density data form baselines for quantifying treatment
      efficacy and set sampling densities for post-treatment assessments. The number of
      plants and insects capable of providing a carbohydrate supply to ants were
      greatest where A. gracilipes was present, but it is not clear if this association
      is causal. Regardless, indirectly controlling ant abundance by controlling
      carbohydrate supply appears to be promising avenue for research. The type of
      targeted, site-specific research such as that described here should be an
      integral part of any eradication program for invasive species to design knowledge
      based treatment protocols and determine assessment benchmarks to achieve
      eradication.

PMID- 24736558
TI  - Evidence for aberrant astrocyte hemichannel activity in Juvenile Neuronal Ceroid
      Lipofuscinosis (JNCL).
AB  - Juvenile Neuronal Ceroid Lipofuscinosis (JNCL) is a lysosomal storage disease
      caused by an autosomal recessive mutation in CLN3 that leads to vision loss,
      progressive cognitive and motor decline, and premature death. Morphological
      evidence of astrocyte activation occurs early in the disease process and
      coincides with regions where neuronal loss eventually ensues. However, the
      consequences of CLN3 mutation on astrocyte function remain relatively ill
      defined. Astrocytes play a critical role in CNS homeostasis, in part, by their
      ability to regulate the extracellular milieu via the formation of extensive
      syncytial networks coupled by gap junction (GJ) channels. In contrast, unopposed
      hemichannels (HCs) have been implicated in CNS pathology by allowing the non
      discriminant passage of molecules between the intracellular and extracellular
      milieus. Here we examined acute brain slices from CLN3 mutant mice
      (CLN3Deltaex7/8) to determine whether CLN3 loss alters the balance of GJ and HC
      activity. CLN3Deltaex7/8 mice displayed transient increases in astrocyte HC
      opening at postnatal day 30 in numerous brain regions, compared to wild type (WT)
      animals; however, HC activity steadily decreased at postnatal days 60 and 90 in
      CLN3Deltaex7/8 astrocytes to reach levels lower than WT cells. This suggested a
      progressive decline in astrocyte function, which was supported by significant
      reductions in glutamine synthetase, GLAST, and connexin expression in
      CLN3Deltaex7/8 mice compared to WT animals. Based on the early increase in
      astrocyte HC activity, CLN3Deltaex7/8 mice were treated with the novel
      carbenoxolone derivative INI-0602 to inhibit HCs. Administration of INI-0602 for
      a one month period significantly reduced lysosomal ceroid inclusions in the
      brains of CLN3Deltaex7/8 mice compared to WT animals, which coincided with
      significant increases in astrocyte GJ communication and normalization of
      astrocyte resting membrane potential to WT levels. Collectively, these findings
      suggest that alterations in astrocyte communication may impact the progression of
      JNCL and could offer a potential therapeutic target. 

PMID- 24736560
TI  - Evaluation of monoclonal antibody-based sandwich direct ELISA (MSD-ELISA) for
      antigen detection of foot-and-mouth disease virus using clinical samples.
AB  - A monoclonal antibody-based sandwich direct ELISA (MSD-ELISA) method was
      previously developed for foot-and-mouth disease (FMD) viral antigen detection.
      Here we evaluated the sensitivity and specificity of two FMD viral antigen
      detection MSD-ELISAs and compared them with conventional indirect sandwich (IS)
      ELISA. The MSD-ELISAs were able to detect the antigen in saliva samples of
      experimentally-infected pigs for a longer term compared to the IS-ELISA. We also
      used 178 RT-PCR-positive field samples from cattle and pigs affected by the 2010
      type-O FMD outbreak in Japan, and we found that the sensitivities of both MSD
      ELISAs were about 7 times higher than that of the IS-ELISA against each sample
      (P<0.01). In terms of the FMD-positive farm detection rate, the sensitivities of
      the MSD-ELISAs were about 6 times higher than that of the IS-ELISA against each
      farm (P<0.01). Although it is necessary to conduct further validation study using
      the other virus strains, MSD-ELISAs could be appropriate as a method to replace
      IS-ELISA for FMD antigen detection. 

PMID- 24736561
TI  - Chemical control of electrical contact to sp2 carbon atoms.
AB  - Carbon-based nanostructures are attracting tremendous interest as components in
      ultrafast electronics and optoelectronics. The electrical interfaces to these
      structures play a crucial role for the electron transport, but the lack of
      control at the atomic scale can hamper device functionality and integration into
      operating circuitry. Here we study a prototype carbon-based molecular junction
      consisting of a single C60 molecule and probe how the electric current through
      the junction depends on the chemical nature of the foremost electrode atom in
      contact with the molecule. We find that the efficiency of charge injection to a
      C60 molecule varies substantially for the considered metallic species, and
      demonstrate that the relative strength of the metal-C bond can be extracted from
      our transport measurements. Our study further suggests that a single-C60 junction
      is a basic model to explore the properties of electrical contacts to meso- and
      macroscopic sp(2) carbon structures. 

PMID- 24736562
TI  - Cortisol biosynthesis in the human ocular surface innate immune response.
AB  - Innate immune responses have a critical role in regulating sight-threatening
      ocular surface (OcS) inflammation. While glucocorticoids (GCs) are frequently
      used to limit tissue damage, the role of intracrine GC (cortisol) bioavailability
      via 11-beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) in OcS defense,
      remains unresolved. We found that primary human corneal epithelial cells (PHCEC),
      fibroblasts (PHKF) and allogeneic macrophages (M1, GM-CSF; M2, M-CSF) were
      capable of generating cortisol (M1>PHKF>M2>PHCEC) but in corneal cells, this was
      independent of Toll-like receptor (TLR) activation. While PolyI?C induced maximal
      cytokine and chemokine production from both PHCEC (IFNgamma, CCL2, CCL3, and
      (CCL4), IL6, CXCL10, CCL5, TNFalpha) and PHKF (CCL2, IL-6, CXCL10, CCL5), only
      PHKF cytokines were inhibited by GCs. Both Poly I?C and LPS challenged-corneal
      cells induced M1 chemotaxis (greatest LPS-PHKF (250%), but down-regulated M1
      11beta-HSD1 activity (30 and 40% respectively). These data were supported by
      clinical studies demonstrating reduced human tear film cortisol?cortisone ratios
      (a biomarker of local 11beta-HSD1 activity) in pseudomonas keratitis (1?2.9)
      versus healthy controls (1?1.3; p<0.05). This contrasted with putative TLR3
      mediated OcS disease (Stevens-Johnson Syndrome, Mucous membrane pemphigoid) where
      an increase in cortisol?cortisone ratio was observed (113.8?1; p<0.05). In
      summary, cortisol biosynthesis in human corneal cells is independent of TLR
      activation and is likely to afford immunoprotection under physiological
      conditions. Contribution to ocular mucosal innate responses is dependent on the
      aetiology of immunological challenge.

PMID- 24736563
TI  - A flow cytometry-based quantitative drug sensitivity assay for all Plasmodium
      falciparum gametocyte stages.
AB  - BACKGROUND: Malaria elimination/eradication campaigns emphasize interruption of
      parasite transmission as a priority strategy. Screening for new drugs and
      vaccines against gametocytes is therefore urgently needed. However, current
      methods for sexual stage drug assays, usually performed by counting or via
      fluorescent markers are either laborious or restricted to a certain stage. Here
      we describe the use of a transgenic parasite line for assaying drug sensitivity
      in all gametocyte stages. METHODS: A transgenic parasite line expressing green
      fluorescence protein (GFP) under the control of the gametocyte-specific gene
      alpha-tubulin II promoter was generated. This parasite line expresses GFP in all
      gametocyte stages. Using this transgenic line, we developed a flow cytometry
      based assay to determine drug sensitivity of all gametocyte stages, and tested
      the gametocytocidal activities of four antimalarial drugs. FINDINGS: This assay
      proved to be suitable for determining drug sensitivity of all sexual stages and
      can be automated. A Z' factor of 0.79 +/- 0.02 indicated that this assay could be
      further optimized for high-throughput screening. The daily sensitivity of
      gametocytes to three antimalarial drugs (chloroquine, dihydroartemisinin and
      pyronaridine) showed a drastic decrease from stage III on, whereas it remained
      relatively steady for primaquine. CONCLUSIONS: A drug assay was developed to use
      a single transgenic parasite line for determining drug susceptibility of all
      gametocyte stages. This assay may be further automated into a high-throughput
      platform for screening compound libraries against P. falciparum gametocytes.

PMID- 24736564
TI  - Circulating HFMD-associated coxsackievirus A16 is genetically and phenotypically
      distinct from the prototype CV-A16.
AB  - Human enteroviruses (HEV) have been linked to hand, foot, and mouth disease
      (HFMD) in the Pacific and Southeast Asia for decades. Many cases of HFMD have
      been attributed to coxsackievirus A16 (CV-A16, CA16), based on only partial viral
      genome determination. Viral phenotypes are also poorly defined. Herein, we have
      genetically and phenotypically characterized multiple circulating CV-A16 viruses
      from HFMD patients and determined multiple full-length sequences of these
      circulating viruses. We discovered that the circulating CV-A16 viruses from HFMD
      patients are genetically distinct from the proto-type CV-A16 G10. We have also
      isolated circulating CV-A16 viruses from hospitalized HFMD patients and compared
      their virological differences. Interestingly, circulating CV-A16 viruses are more
      pathogenic in a neonatal mouse model than is CV-A16 G10. Thus, we have found
      circulating recombinant forms of CV-A16 (CRF CV-A16) that are related to, but
      different from, the prototype CV-A16 G10 that have distinct biological
      phenotypes. 

PMID- 24736566
TI  - Specific localization and measurement of hydrogen peroxide in Arabidopsis
      thaliana cell suspensions and protoplasts elicited by COS-OGA.
AB  - H2O2 acts as an important signaling molecule during plant/pathogen interactions
      but its study remains a challenge due to the current shortcomings in H2O2
      responsive probes. In this work, ContPY1, a new molecular probe developed to
      specifically detect H2O2 was used to study the elicitation of Arabidopsis
      thaliana cells by a complex of chitosan oligomers (COS) and oligogalacturonides
      (OGA). The comparison of cell suspensions, protoplasts of cell suspensions and
      leaf protoplasts treated with different inhibitors gave indications on the
      potential sources of hydrogen peroxide in plant cells. The relative contribution
      of the cell wall, of membrane dehydrogenases and of peroxidases depended on cell
      type and treatment and proved to be variable. Our present protocol can be used to
      study hydrogen peroxide production in a large variety of plant species by simple
      protocol adaptation.

PMID- 24736567
TI  - Distorted self-perceived weight status and underestimation of weight status in
      diabetes mellitus type 2 patients.
AB  - OBJECTIVES: Diabetes mellitus type 2 (DM 2) patients' self-perception of their
      weight status is very critical in diabetes care. We sought to investigate
      perception of weight status in a sample of 200 DM 2 patients attending an
      outpatient clinic at a Teaching Hospital and compared it with their BMI-measured
      weight status, with a focus on underestimation of their weight status. Factors
      associated with underestimation of weight status in this sample were also
      explored. METHODS: Using a cross-sectional design, anthropometric and clinical
      variables were assessed using appropriate tools. Questionnaires were used to
      collect socio-demographic data and self-perception of weight status. Self
      perceived weight status was compared to BMI-measured weight status by cross
      tabulation, Kappa statistics of agreement and chi2 for trend analysis. Both
      univariate and multiple logistic regression analysis were conducted to identify
      factors associated with underestimation of weight status. RESULTS: The prevalence
      of general overweight/obesity and abdominal obesity was 32.0% (n = 64) and 58.0%
      (n = 116) respectively. Generally, 58.0% (n = 116) of the participants had a
      distorted weight perceived weight status in which 77.6% (n = 90) underestimated
      their weight status. Factors associated with underestimation of weight status
      were being overweight/obese (AOR = 22.9, 95% CI = 8.30-63.07, p<0.001), not
      married (AOR = 3.7, 95% CI = 1.50-9.17, p = 0.005) and never tried to lose weight
      (AOR = 6.9, 95% CI = 2.35-19.97, p<0.001). Participants aged over 40 years and
      those being hyperglycaemic were not significantly associated to underestimation
      of weight status. CONCLUSION: We found a substantial discordance between BMI
      measured and self-perceived weight status. Factors that were associated with
      underestimation of weight status were being; overweight/obese, not married and
      never tried to lose weight. Diabetes patients should be provided with information
      about weight guidelines.

PMID- 24736568
TI  - Activation of GPER-1 estradiol receptor downregulates production of testosterone
      in isolated rat Leydig cells and adult human testis.
AB  - PURPOSE: Estradiol (E2) modulates testicular functions including steroidogenesis,
      but the mechanisms of E2 signaling in human testis are poorly understood. GPER-1
      (GPR30), a G protein-coupled membrane receptor, mediates rapid genomic and non
      genomic response to estrogens. The aim of this study was to evaluate GPER-1
      expression in the testis, and its role in estradiol dependent regulation of
      steroidogenesis in isolated rat Leydig cells and human testis. MATERIALS AND
      METHODS: Isolated Leydig cells (LC) from adult rats and human testicular tissue
      were used in this study. Expression and localization studies of GPER-1 were
      performed with qRT-PCR, immunofluorescence, immunohistochemistry and Western
      Blot. Luteinizing Hormone (LH) -stimulated, isolated LC were incubated with
      estradiol, G-1 (GPER-1-selective agonist), and estrogen receptor antagonist ICI
      182,780. Testosterone production was measured with radioimmunoassay. LC viability
      after incubation with G-1 was measured using 3-(4,5-dimethylthiazol-2-yl)-5-(3
      carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt (MTS) assay.
      RESULTS: GPER-1 mRNA is abundantly expressed in rat LC and human testis. Co
      localization experiments showed high expression levels of GPER-1 protein in LC.
      E2-dependent activation of GPER-1 lowers testosterone production in isolated rats
      LCs and in human testis, with statistically and clinically significant drops in
      testosterone production by 20-30% as compared to estradiol-naive LC. The exposure
      to G-1 does not affect viability of isolated LCs. CONCLUSIONS: Our results
      indicate that activation of GPER-1 lowers testosterone levels in the rat and
      human testis. The expression of GPER-1 in human testis, which lack ERalpha, makes
      it an exciting target for developing new agents affecting testosterone production
      in men.

PMID- 24736569
TI  - National patterns in environmental injustice and inequality: outdoor NO2 air
      pollution in the United States.
AB  - We describe spatial patterns in environmental injustice and inequality for
      residential outdoor nitrogen dioxide (NO2) concentrations in the contiguous
      United States. Our approach employs Census demographic data and a recently
      published high-resolution dataset of outdoor NO2 concentrations. Nationally,
      population-weighted mean NO2 concentrations are 4.6 ppb (38%, p<0.01) higher for
      nonwhites than for whites. The environmental health implications of that
      concentration disparity are compelling. For example, we estimate that reducing
      nonwhites' NO2 concentrations to levels experienced by whites would reduce
      Ischemic Heart Disease (IHD) mortality by ~7,000 deaths per year, which is
      equivalent to 16 million people increasing their physical activity level from
      inactive (0 hours/week of physical activity) to sufficiently active (>2.5
      hours/week of physical activity). Inequality for NO2 concentration is greater
      than inequality for income (Atkinson Index: 0.11 versus 0.08). Low-income
      nonwhite young children and elderly people are disproportionately exposed to
      residential outdoor NO2. Our findings establish a national context for previous
      work that has documented air pollution environmental injustice and inequality
      within individual US metropolitan areas and regions. Results given here can aid
      policy-makers in identifying locations with high environmental injustice and
      inequality. For example, states with both high injustice and high inequality (top
      quintile) for outdoor residential NO2 include New York, Michigan, and Wisconsin. 

PMID- 24736570
TI  - A drug delivery strategy: binding enkephalin to asialoglycoprotein receptor by
      enzymatic galactosylation.
AB  - Glycosylation of biopharmaceuticals can mediate cell specific delivery by
      targeting carbohydrate receptors. Additionally, glycosylation can improve the
      physico-chemical (drug-like) properties of peptide based drug candidates. The
      main purpose of this study was to examine if glycosylation of the peptide
      enkephalin could facilitate its binding to the carbohydrate receptor,
      asialoglycoprotein. Firstly, we described the one-pot enzymatic galactosylation
      of lactose modified enkephalin in the presence of uridine-5'-diphosphogalactose 4
      epimerase and lipopolysaccharyl alpha-1,4-galactosyltransferase. Stability
      experiments using human plasma and Caco-2 cell homogenates showed that
      glycosylation considerably improved the stability of enkephalin (at least 60%
      remained stable after a 2 hr incubation at 37 degrees C). In vitro permeability
      experiments using Caco-2 cells revealed that the permeability of mono- and
      trisaccharide conjugated enkephalins was 14 and 28 times higher, respectively,
      than that of enkephalin alone (Papp 3.1*10-8 cm/s). By the methods of surface
      plasmon resonance and molecular modeling, we demonstrated that the enzymatic
      glycosylation of enkephalin enabled binding the asialoglycoprotein receptor. The
      addition of a trisaccharide moiety to enkephalin improved the binding of
      enkephalin to the asialoglycoprotein receptor two fold (KD = 91 uM). The docking
      scores from molecular modeling showed that the binding modes and affinities of
      the glycosylated enkephalin derivatives to the asialoglycoprotein receptor
      complemented the results from the surface plasmon resonance experiments.

PMID- 24736571
TI  - Phylogenetic variation of phytolith carbon sequestration in bamboos.
AB  - Phytoliths, the amorphous silica deposited in plant tissues, can occlude organic
      carbon (phytolith-occluded carbon, PhytOC) during their formation and play a
      significant role in the global carbon balance. This study explored phylogenetic
      variation of phytolith carbon sequestration in bamboos. The phytolith content in
      bamboo varied substantially from 4.28% to 16.42%, with the highest content in
      Sasa and the lowest in Chimonobambusa, Indocalamus and Acidosasa. The mean PhytOC
      production flux and rate in China's bamboo forests were 62.83 kg CO2 ha(-1) y(-1)
      and 4.5 * 10(8)kg CO2 y(-1), respectively. This implies that 1.4 * 10(9) kg CO2
      would be sequestered in world's bamboo phytoliths because the global bamboo
      distribution area is about three to four times higher than China's bamboo.
      Therefore, both increasing the bamboo area and selecting high phytolith-content
      bamboo species would increase the sequestration of atmospheric CO2 within bamboo
      phytoliths.

PMID- 24736573
TI  - Progress in prevention: motivating our patients to adopt and maintain healthy
      lifestyles.

PMID- 24736574
TI  - Summaries of nursing care-related systematic reviews from the Cochrane library:
      pharmacotherapy for hypertension in the elderly.

PMID- 24736575
TI  - The safety and efficacy of statin therapy in the pediatric population.
AB  - New guidelines from the American Academy of Pediatrics now recommend the
      consideration of statin therapy as a first-line pharmacological measure in
      children as young as 8 years old with marked hypercholesterolemia. Thus, it is
      important to review both the safety and efficacy of initiating statin therapy
      prior to adulthood. Statins interfere with cholesterol synthesis, thereby
      lowering serum cholesterol levels. However, there are special considerations that
      need to be made when initiating medications such as statins in the pediatric
      population. Cholesterol is crucial for various biologic processes including
      neurological development. Cholesterol also serves as a biochemical precursor to
      many hormones including those critical in sexual development. This article
      examines the current evidence for the safety and efficacy of statin use in the
      pediatric population and identifies areas for future research. 

PMID- 24736577
TI  - Compression therapy: a dramatic intervention in health care.
AB  - Over the past few decades, there has been a growing appreciation of the impact of
      leg ulceration on all aspects of a patient's life. Particular issues include
      uncontrolled pain, lack of sleep, odour, emotional problems and reduced mobility.

PMID- 24736576
TI  - A novel hyaluronidase produced by Bacillus sp. A50.
AB  - Hyaluronidases are a family of enzymes that degrade hyaluronic acid (hyaluronan,
      HA) and widely used in many fields. A hyaluronidase producing bacteria strain was
      screened from the air. 16S ribosomal DNA (16S rDNA) analysis indicated that the
      strain belonged to the genus Bacillus, and the strain was named as Bacillus sp.
      A50. This is the first report of a hyaluronidase from Bacillus, which yields
      unsaturated oligosaccharides as product like other microbial hyaluronate lyases.
      Under optimized conditions, the yield of hyaluronidase from Bacillus sp. A50
      could reach up to 1.5*10(4) U/mL, suggesting that strain A50 is a good producer
      of hyaluronidase. The hyaluronidase (HAase-B) was isolated and purified from the
      bacterial culture, with a specific activity of 1.02*10(6) U/mg protein and a
      yield of 25.38%. The optimal temperature and pH of HAase-B were 44 degrees C and
      pH 6.5, respectively. It was stable at pH 5-6 and at a temperature lower than 45
      degrees C. The enzymatic activity could be enhanced by Ca2+, Mg2+, or Ni2+, and
      inhibited by Zn2+, Cu2+, EDTA, ethylene glycol tetraacetic acid (EGTA),
      deferoxamine mesylate salt (DFO), triton X-100, Tween 80, or SDS at different
      levels. Kinetic measurements of HAase-B towards HA gave a Michaelis constant (Km)
      of 0.02 mg/mL, and a maximum velocity (Vmax) of 0.27 A232/min. HAase-B also
      showed activity towards chondroitin sulfate A (CSA) with the kinetic parameters,
      Km and Vmax, 12.30 mg/mL and 0.20 A232/min respectively. Meanwhile, according to
      the sequences of genomic DNA and HAase-B's part peptides, a 3,324-bp gene
      encoding HAase-B was obtained.

PMID- 24736578
TI  - Safety, tolerability and acceptability of KTwo.
AB  - Part 1 of the KTwo evidence review concerned the efficacy and reproducibility of
      the bandage system in the management of leg ulceration and lymphoedema. Here, in
      Part 2, the focus shifts to its tolerability and acceptability to both patients
      and clinicians. The evidence presented here ranges from a randomised controlled
      trial to anecdotal reports in conference posters. The aim of this review is to
      describe the evidence, and not to critique it. 

PMID- 24736580
TI  - Comment on 'The NQO1 polymorphism C609T (Pro187Ser) and cancer susceptibility: a
      comprehensive meta-analysis'.

PMID- 24736579
TI  - Gemcitabine-oxaliplatin plus prednisolone is active in patients with castration
      resistant prostate cancer for whom docetaxel-based chemotherapy failed.
AB  - BACKGROUND: There has been no previous study on the activity of gemcitabine in
      combination with oxaliplatin (GemOx) for castration-resistant prostate cancer
      (CRPC). METHODS: The GemOx was preclinically tested for cytotoxic activity in
      human prostate cancer cell lines. Clinically, patients with CRPC who failed prior
      docetaxel were treated with gemcitabine 1000 mg m(-2) and oxaliplatin 100 mg m(
      2) intravenously every 2 weeks and prednisolone 5 mg orally twice daily. The
      primary end point was the prostate-specific antigen (PSA) response rate. RESULTS:
      The GemOx displayed synergistic effects based on Chou and Talalay analysis. In
      the phase II study, 33 patients were accrued. The median dose of docetaxel
      exposure was 518 mg m(-2). A total of 270 cycles were administered with a median
      of eight cycles per patient. A PSA response rate was 55% (95% CI, 38-72) and
      radiologic response rate was 82% (9 out of 11). With a median follow-up duration
      of 20.5 months, the median time to PSA progression was 5.8 months (95% CI, 4.4
      7.2) and the median overall survival was 17.6 months (95% CI, 12.6-22.6). The
      most frequently observed grade 3 or 4 toxicities were neutropenia (13%) and
      thrombocytopenia (13%). CONCLUSIONS: The GemOx is active and tolerable in
      patients with metastatic CRPC after docetaxel failure (NCT 01487720).

PMID- 24736581
TI  - Pharmacokinetically guided sunitinib dosing: a feasibility study in patients with
      advanced solid tumours.
AB  - BACKGROUND: Plasma exposure of sunitinib shows large inter-individual variation.
      Therefore, a pharmacokinetic (PK) study was performed to determine safety and
      feasibility of sunitinib dosing based on PK levels. METHODS: Patients were
      treated with sunitinib 37.5 mg once daily. At days 15 and 29 of treatment, plasma
      trough levels of sunitinib and N-desethyl sunitinib were measured. If the total
      trough level (TTL) was <50 ng ml(-1) and the patient did not show any grade ?3
      toxicity, the daily sunitinib dose was increased by 12.5 mg. If the patient
      suffered from grade ?3 toxicity, the sunitinib dose was lowered by 12.5 mg.
      RESULTS: Twenty-nine out of 43 patients were evaluable for PK assessments. Grade
      ?3 adverse events were experienced in seven patients (24%) at the starting dose
      and in nine patients (31%) after dose escalation. TTLs were below target in 15
      patients (52%) at the starting dose. Of these, five patients (17%) reached target
      TTL after dose escalation without additional toxicity. CONCLUSIONS: In a third of
      the patients that were below target TTL at standard dose, the sunitinib dose
      could be increased without additional toxicities. This could be the basis for
      future studies and the implementation of a PK-guided dosing strategy in clinical
      practice.

PMID- 24736583
TI  - Reply: Comment on 'The NQO1 polymorphism C609T (Pro187Ser) and cancer
      susceptibility: a comprehensive meta-analysis'.

PMID- 24736582
TI  - Introduction and sustained high coverage of the HPV bivalent vaccine leads to a
      reduction in prevalence of HPV 16/18 and closely related HPV types.
AB  - BACKGROUND: In 2008, a national human papillomavirus (HPV) immunisation programme
      began in Scotland for 12-13 year old females with a three-year catch-up campaign
      for those under the age of 18. Since 2008, three-dose uptake of bivalent vaccine
      in the routine cohort aged 12-13 has exceeded 90% annually, while in the catch-up
      cohort overall uptake is 66%. METHODS: To monitor the impact of HPV immunisation,
      a programme of national surveillance was established (pre and post introduction)
      which included yearly sampling and HPV genotyping of women attending for cervical
      screening at age 20. By linking individual vaccination, screening and HPV testing
      records, we aim to determine the impact of the immunisation programme on
      circulating type-specific HPV infection particularly for four outcomes: (i) the
      vaccine types HPV 16 or 18 (ii) types considered to be associated with cross
      protection: HPV 31, 33 or 45; (iii) all other high-risk types and (iv) any HPV.
      RESULTS: From a total of 4679 samples tested, we demonstrate that three doses
      (n=1100) of bivalent vaccine are associated with a significant reduction in
      prevalence of HPV 16 and 18 from 29.8% (95% confidence interval 28.3, 31.3%) to
      13.6% (95% confidence interval 11.7, 15.8%). The data also suggest cross
      protection against HPV 31, 33 and 45. HPV 51 and 56 emerged as the most prevalent
      (10.5% and 9.6%, respectively) non-vaccine high-risk types in those vaccinated,
      but at lower rates than HPV 16 (25.9%) in those unvaccinated. CONCLUSIONS: This
      data demonstrate the positive impact of bivalent vaccination on the prevalence of
      HPV 16, 18, 31, 33 and 45 in the target population and is encouraging for
      countries which have achieved high-vaccine uptake.

PMID- 24736584
TI  - What is the role of routine follow-up for localised limb soft tissue sarcomas? A
      retrospective analysis of 174 patients.
AB  - BACKGROUND: There are neither prospective data nor agreement on the optimal
      routine follow-up procedures in patients treated for soft tissue sarcoma of the
      limb. METHODS: Data on 174 consecutive patients with a soft tissue sarcoma of the
      limb undergoing follow-up by oncologists at a single centre from 2003 to 2009
      were included in this analysis. The rate and site of recurrence and mode of
      detection were analysed. Outcome of the patients was assessed. RESULTS: Eighty
      two patients (47%) experienced relapse of any type. Isolated local recurrence
      occurred in 26 patients and local relapse with synchronous pulmonary metastases
      in five patients. Local recurrences were detected clinically in 30 of these 31
      patients; magnetic resonance imaging identified only one local recurrence. Twenty
      eight patients developed isolated lung metastases; in nine patients these were
      amenable to resections, seven of whom are currently free of disease after
      treatment. Lung metastases were detected by chest x-ray (CXR) in 19 patients,
      computed tomography scanning in 3 patients, and clinically in 11 patients. Twenty
      three patients developed non-pulmonary metastases. More than 80% of relapses
      occurred in the first 2 years of follow-up; however, later recurrences were also
      observed. CONCLUSIONS: Routine follow-up CXR can detect lung metastases suitable
      for surgical resection, although the optimal interval of imaging has yet to be
      defined. Local relapse is almost always detected by patients or physicians, and
      routine scanning of the primary site is of doubtful benefit. Patient and
      physician education to detect local relapse may be helpful. Prospective
      evaluation of follow-up is recommended.

PMID- 24736585
TI  - Efficacy and toxicity of external-beam radiation therapy for localised prostate
      cancer: a network meta-analysis.
AB  - BACKGROUND: Many radiation regimens for treating prostate cancer have been used
      over the years, but which regimen is optimal for localised or locally advanced
      prostate cancer lacks consensus. We performed a network meta-analysis to identify
      the optimal radiation regimen. METHODS: We systematically reviewed data from 27
      randomised controlled trials and could group seven radiation regimens as follows:
      low- and high-dose radiation therapy (LDRT and HDRT), LDRT+ short- or long-term
      androgen deprivation therapy (LDRT+SADT and LDRT+LADT), HDRT+SADT,
      hypofractionated radiotherapy (HFRT), and HFRT+SADT. The main outcomes were
      overall mortality (OM), prostate-specific antigen (PSA) failure, cancer-specific
      mortality, and adverse events. RESULTS: For the network meta-analysis of 27
      trials, LDRT+LADT and LDRT+SADT were associated with decreased risk of OM as
      compared with LDRT alone as was LDRT+LADT compared with HDRT. Apart from HFRT,
      all other treatments were associated with decreased risk of PSA failure as
      compared with LDRT. HFRT+SADT was associated with decreased risk of cancer
      specific mortality as compared with HFRT, LDRT+SADT, HDRT, and LDRT. CONCLUSIONS:
      HFRT+SADT therapy might be the most efficacious treatment but with worst toxicity
      for localised or locally advanced prostate cancer, and HDRT showed excellent
      efficacy but more adverse events.

PMID- 24736586
TI  - The combination of strong expression of ZNF143 and high MIB-1 labelling index
      independently predicts shorter disease-specific survival in lung adenocarcinoma.
AB  - BACKGROUND: The transcription factor, zinc finger protein 143 (ZNF143),
      positively regulates many cell-cycle-related genes. The ZNF143 would show high
      expression of multiple solid tumours related closely to cancer cell growth,
      similar to the widely accepted Ki67 (MIB-1) protein, but the underlying
      mechanisms for ZNF143 remain unclear. We investigated the association of ZNF143
      expression with clinicopathological features and prognoses of patients with lung
      adenocarcinoma. METHODS: Expressions of ZNF143 and MIB-1 were
      immunohistochemically analysed in 183 paraffin-embedded tumour samples of
      patients with lung adenocarcinoma. The ZNF143 expression was considered to be
      strong when >30% of the cancer cells demonstrated positive staining. RESULTS:
      Strong ZNF143+ expression showed a significantly close relationship to
      pathologically moderate to poor differentiation and highly invasive
      characteristics. The ZNF143 positivity potentially induced cell growth of lung
      adenocarcinoma, correlated significantly with high MIB-1 labelling index (?10%).
      Univariate and multivariate analyses demonstrated that both strong ZNF143+ and
      the high MIB-1 index group have only and significantly worse survival rates.
      CONCLUSIONS: The combination of strong ZNF143 expression and high MIB-1 index
      potentially predicts high proliferating activity and poor prognosis in patients
      with lung adenocarcinoma, and may offer a therapeutic target against ZNF143.

PMID- 24736587
TI  - Spectrum of very early breast cancer in a setting without organised screening.
AB  - BACKGROUND: Within a setting without organised breast cancer screening, the
      characteristics and survival of very early breast cancer were determined.
      METHODS: All 4930 women diagnosed with breast cancer in University Malaya Medical
      Center, Malaysia from 1993 to 2011 were included. Factors associated with very
      early presentation (stage I) at diagnosis were identified. Tumour
      characteristics, management patterns, and survival of very early breast cancer
      were described, and where appropriate, compared with other settings. RESULTS:
      Proportion of women presenting with stage I breast cancer significantly increased
      from 15.2% to 25.2% over two decades. Factors associated with very early
      presentation were Chinese ethnicity, positive family history of breast cancer,
      and recent period of diagnosis. Within stage I breast cancers, median tumour size
      at presentation was 1.5 cm. A majority of stage I breast cancer patients received
      mastectomy, which was associated with older age, Chinese ethnicity,
      postmenopausal status, and larger tumours. Chemotherapy was administered in 36%
      of patients. Five-year age-adjusted relative survival for women with stage I
      breast cancer was 99.1% (95% CI: 97.6-99.6%). CONCLUSIONS: The proportion of
      women presenting with very early breast cancer in this setting without organised
      screening is increasing. These women seem to survive just as well as their
      counterparts from affluent settings.

PMID- 24736588
TI  - Tissue inhibitor of metalloproteinase-3 knockout mice exhibit enhanced energy
      expenditure through thermogenesis.
AB  - Tissue inhibitors of metalloproteinases (TIMPs) regulate matrix metalloproteinase
      activity and maintain extracellular matrix homeostasis. Although TIMP-3 has
      multiple functions (e.g., apoptosis, inhibition of VEGF binding to VEGF receptor,
      and inhibition of TNFalpha converting enzyme), its roles in thermogenesis and
      metabolism, which influence energy expenditure and can lead to the development of
      metabolic disorders when dysregulated, are poorly understood. This study aimed to
      determine whether TIMP-3 is implicated in metabolism by analyzing TIMP-3 knockout
      (KO) mice. TIMP-3 KO mice had higher body temperature, oxygen consumption, and
      carbon dioxide production than wild-type (WT) mice, although there were no
      differences in food intake and locomotor activity. These results suggest that
      metabolism is enhanced in TIMP-3 KO mice. Real-time PCR analysis showed that the
      expression of PPAR-delta, UCP-2, NRF-1 and NRF-2 in soleus muscle, and PGC-1alpha
      and UCP-2 in gastrocnemius muscle, was higher in TIMP-3 KO mice than in WT mice,
      suggesting that TIMP-3 deficiency may increase mitochondrial activity. When
      exposed to cold for 8 hours to induce thermogenesis, TIMP-3 KO mice had a higher
      body temperature than WT mice. In the treadmill test, oxygen consumption and
      carbon dioxide production were higher in TIMP-3 KO mice both before and after
      starting exercise, and the difference was more pronounced after starting
      exercise. Our findings suggest that TIMP-3 KO mice exhibit enhanced metabolism,
      as reflected by a higher body temperature than WT mice, possibly due to increased
      mitochondrial activity. Given that TIMP-3 deficiency increases energy
      expenditure, TIMP-3 may present a novel therapeutic target for preventing
      metabolic disorders. 

PMID- 24736589
TI  - The contribution of qualitative CEUS to the determination of malignancy in
      adnexal masses, indeterminate on conventional US - a multicenter study.
AB  - The aim of this study is to evaluate the efficacy of qualitative analysis of
      contrast-enhanced ultrasound (CEUS) in discrimination of adnexal masses which
      were undetermined by conventional ultrasound (US). A total of 120 patients
      underwent transabdominal CEUS. The initial enhancement time and intensity
      compared with the uterine myometrium, contrast agent distribution patterns and
      dynamic changes of enhancement were assessed. The sensitivity (Sen), specificity
      (Spe), positive predictive value (PPV), negative predictive value (NPV), accuracy
      (ACC) and Youden's index were calculated for contrast variables. The gold
      standard was the histological diagnosis. There were 48 malignant tumors and 72
      benign tumors. The enhancement features of malignant masses were different from
      benign ones. Earlier or simultaneous enhancement with inhomogeneous enhancement
      yielded the highest capability in differential diagnosis, and Sen, Spe, PPV, NPV,
      ACC, Youden's index was 89.6%, 97.2%, 93.2%, 95.6%, 93.3%, and 0.88,
      respectively. The qualitative evaluation of CEUS is useful in the differential
      diagnosis of adnexal masses where conventional US is indeterminate. 

PMID- 24736591
TI  - Assessment of the soil organic carbon sink in a project for the conversion of
      farmland to forestland: a case study in Zichang county, Shaanxi, China.
AB  - The conversion of farmland to forestland not only changes the ecological
      environment but also enriches the soil with organic matter and affects the global
      carbon cycle. This paper reviews the influence of land use changes on the soil
      organic carbon sink to determine whether the Chinese "Grain-for-Green"
      (conversion of farmland to forestland) project increased the rate of SOC content
      during its implementation between 1999 and 2010 in the hilly and gully areas of
      the Loess Plateau in north-central China. The carbon sink was quantified, and the
      effects of the main species were assessed. The carbon sink increased from
      2.26*106 kg in 1999 to 8.32*106 kg in 2010 with the sustainable growth of the
      converted areas. The black locust (Robinia pseudoacacia L.) and alfalfa (Medicago
      sativa L.) soil increased SOC content in the top soil (0-100 cm) in the initial 7
      yr period, while the sequestration occurred later (>7 yr) in the 100-120 cm layer
      after the "Grain-for-Green" project was implemented. The carbon sink function
      measured for the afforested land provides evidence that the Grain-for-Green
      project has successfully excavated the carbon sink potential of the Shaanxi
      province and served as an important milestone for establishing an effective
      organic carbon management program. 

PMID- 24736592
TI  - Increased SOX2 gene copy number is associated with FGFR1 and PIK3CA gene gain in
      non-small cell lung cancer and predicts improved survival in early stage disease.
AB  - BACKGROUND: We aimed to investigate prevalence and prognostic role of SOX2,
      PIK3CA, FGFR1 and BRF2 gene gain in patients with surgically resected non-small
      cell lung cancer (NSCLC). METHODS: SOX2, PIK3CA, FGFR1 and BRF2 gene copy number
      was assessed by fluorescence in situ hybridization (FISH) in arrayed tissue cores
      from 447 resected NSCLCs. RESULTS: Increased gene copy number (FISH+) for SOX2,
      PIK3CA, FGFR1 and BRF2 was observed in 23.6%, 29.2%, 16.6% and 14.9% of cases,
      respectively. FISH+ status for each gene was significantly associated with
      smoking history, squamous cell carcinoma (SCC) histology, and increased copy
      number of the other studied genes. Multivariate analysis of overall survival
      indicated increased SOX2 gene copy number (P = 0.008), stage I-II (P<0.001), and
      adenocarcinoma or SCC histology (P = 0.016) as independent, favorable prognostic
      factors. A statistically significant interaction was observed between stage and
      SOX2 gene status (P = 0.021), indicating that the prognostic impact of SOX2 gene
      gain differs across stages and is limited to patients with stage I-II disease (HR
      0.44, 95% CI: 0.25-0.77; P = 0.004, adjusted for histology). CONCLUSIONS:
      Increased SOX2 gene copy number is an independent and favorable prognostic factor
      in surgically resected, early stage NSCLC, regardless of histology. SOX2, PIK3CA,
      FGFR1 and BRF2 gene gains are likely to occur concurrently, with potentially
      relevant implications for the development of new therapeutic strategies.

PMID- 24736593
TI  - Transcriptional regulators of legume-rhizobia symbiosis: nuclear factors Ys and
      GRAS are two for tango.
AB  - Transcription factors are DNA binding proteins that regulate gene expression. The
      nitrogen fixing symbiosis established between legume plants and soil bacteria is
      a complex interaction, in which plants need to integrate signals derived from the
      symbiont and the surrounding environment to initiate the developmental program of
      nodule organogenesis and the infection process. Several transcription factors
      that play critical roles in these processes have been reported in the past
      decade, including proteins of the GRAS and NF-Y families. Recently, we reported
      the characterization of a new GRAS domain containing-protein that interacts with
      a member of the C subunit of the NF-Y family, which plays an important role in
      nodule development and the progression of bacterial infection during the
      symbiotic interaction. The connection between transcription factors of these
      families highlights the significance of multimeric complexes in the fabulous
      capacity of plants to integrate and respond to multiple environmental stimuli. 

PMID- 24736594
TI  - Convergence time towards periodic orbits in discrete dynamical systems.
AB  - We investigate the convergence towards periodic orbits in discrete dynamical
      systems. We examine the probability that a randomly chosen point converges to a
      particular neighborhood of a periodic orbit in a fixed number of iterations, and
      we use linearized equations to examine the evolution near that neighborhood. The
      underlying idea is that points of stable periodic orbit are associated with
      intervals. We state and prove a theorem that details what regions of phase space
      are mapped into these intervals (once they are known) and how many iterations are
      required to get there. We also construct algorithms that allow our theoretical
      results to be implemented successfully in practice. 

PMID- 24736596
TI  - Negatively-biased credulity and the cultural evolution of beliefs.
AB  - The functions of cultural beliefs are often opaque to those who hold them.
      Accordingly, to benefit from cultural evolution's ability to solve complex
      adaptive problems, learners must be credulous. However, credulity entails costs,
      including susceptibility to exploitation, and effort wasted due to false beliefs.
      One determinant of the optimal level of credulity is the ratio between the costs
      of two types of errors: erroneous incredulity (failing to believe information
      that is true) and erroneous credulity (believing information that is false). This
      ratio can be expected to be asymmetric when information concerns hazards, as the
      costs of erroneous incredulity will, on average, exceed the costs of erroneous
      credulity; no equivalent asymmetry characterizes information concerning benefits.
      Natural selection can therefore be expected to have crafted learners' minds so as
      to be more credulous toward information concerning hazards. This negatively
      biased credulity extends general negativity bias, the adaptive tendency for
      negative events to be more salient than positive events. Together, these biases
      constitute attractors that should shape cultural evolution via the aggregated
      effects of learners' differential retention and transmission of information. In
      two studies in the U.S., we demonstrate the existence of negatively-biased
      credulity, and show that it is most pronounced in those who believe the world to
      be dangerous, individuals who may constitute important nodes in cultural
      transmission networks. We then document the predicted imbalance in cultural
      content using a sample of urban legends collected from the Internet and a sample
      of supernatural beliefs obtained from ethnographies of a representative
      collection of the world's cultures, showing that beliefs about hazards
      predominate in both. 

PMID- 24736597
TI  - Gastro-esophageal reflux disease symptoms and demographic factors as a pre
      screening tool for Barrett's esophagus.
AB  - BACKGROUND: Barrett's esophagus (BE) occurs as consequence of reflux and is a
      risk factor for esophageal adenocarcinoma. The current "gold-standard" for
      diagnosing BE is endoscopy which remains prohibitively expensive and impractical
      as a population screening tool. We aimed to develop a pre-screening tool to aid
      decision making for diagnostic referrals. METHODOLOGY/PRINCIPAL FINDINGS: A
      prospective (training) cohort of 1603 patients attending for endoscopy was used
      for identification of risk factors to develop a risk prediction model. Factors
      associated with BE in the univariate analysis were selected to develop prediction
      models that were validated in an independent, external cohort of 477 non-BE
      patients referred for endoscopy with symptoms of reflux or dyspepsia. Two
      prediction models were developed separately for columnar lined epithelium (CLE)
      of any length and using a stricter definition of intestinal metaplasia (IM) with
      segments >= 2 cm with areas under the ROC curves (AUC) of 0.72 (95%CI: 0.67-0.77)
      and 0.81 (95%CI: 0.76-0.86), respectively. The two prediction models included
      demographics (age, sex), symptoms (heartburn, acid reflux, chest pain, abdominal
      pain) and medication for "stomach" symptoms. These two models were validated in
      the independent cohort with AUCs of 0.61 (95%CI: 0.54-0.68) and 0.64 (95%CI: 0.52
      0.77) for CLE and IM >= 2 cm, respectively. CONCLUSIONS: We have identified and
      validated two prediction models for CLE and IM >= 2 cm. Both models have fair
      prediction accuracies and can select out around 20% of individuals unlikely to
      benefit from investigation for Barrett's esophagus. Such prediction models have
      the potential to generate useful cost-savings for BE screening among the
      symptomatic population.

PMID- 24736598
TI  - Effects of 12 weeks high-intensity & reduced-volume training in elite athletes.
AB  - It was investigated if high-intensity interval training (HIT) at the expense of
      total training volume improves performance, maximal oxygen uptake and swimming
      economy. 41 elite swimmers were randomly allocated to a control (CON) or HIT
      group. For 12 weeks both groups trained ~12 h per week. HIT comprised ~5 h vs. 1
      h and total distance was ~17 km vs. 35 km per week for HIT and CON, respectively.
      HIT was performed as 6-10*10-30 s maximal effort interspersed by 2-4 minutes of
      rest. Performance of 100 m all-out freestyle and 200 m freestyle was similar
      before and after the intervention in both HIT (60.4+/-4.0 vs. 60.3+/-4.0 s; n =
      13 and 133.2+/-6.4 vs. 132.6+/-7.7 s; n = 14) and CON (60.2+/-3.7 vs. 60.6+/-3.8
      s; n = 15 and 133.5+/-7.0 vs. 133.3+/-7.6 s; n = 15). Maximal oxygen uptake
      during swimming was similar before and after the intervention in both the HIT
      (4.0+/-0.9 vs. 3.8+/-1.0 l O2*min-1; n = 14) and CON (3.8+/-0.7 vs. 3.8+/-0.7 l
      O2*min-1; n = 11) group. Oxygen uptake determined at fixed submaximal speed was
      not significantly affected in either group by the intervention. Body fat % tended
      to increase (P = 0.09) in the HIT group (15.4+/-1.6% vs. 16.3+/-1.6%; P = 0.09; n
      = 16) and increased (P<0.05) in the CON group (13.9+/-1.5% vs. 14.9+/-1.5%; n =
      17). A distance reduction of 50% and a more than doubled HIT amount for 12 weeks
      did neither improve nor compromise performance or physiological capacity in elite
      swimmers.

PMID- 24736599
TI  - The LIM-only protein FHL2 reduces vascular lesion formation involving inhibition
      of proliferation and migration of smooth muscle cells.
AB  - The LIM-only protein FHL2, also known as DRAL or SLIM3, has a function in fine
      tuning multiple physiological processes. FHL2 is expressed in the vessel wall in
      smooth muscle cells (SMCs) and endothelial cells and conflicting data have been
      reported on the regulatory function of FHL2 in SMC phenotype transition. At
      present the function of FHL2 in SMCs in vascular injury is unknown. Therefore, we
      studied the role of FHL2 in SMC-rich lesion formation. In response to carotid
      artery ligation FHL2-deficient (FHL2-KO) mice showed accelerated lesion formation
      with enhanced Ki67 expression compared with wild-type (WT)-mice. Consistent with
      these findings, cultured SMCs from FHL2-KO mice showed increased proliferation
      through enhanced phosphorylation of extracellular-regulated kinase-1/2 (ERK1/2)
      and induction of CyclinD1 expression. Overexpression of FHL2 in SMCs inhibited
      CyclinD1 expression and CyclinD1-knockdown blocked the enhanced proliferation of
      FHL2-KO SMCs. We also observed increased CyclinD1 promoter activity in FHL2-KO
      SMCs, which was reduced upon ERK1/2 inhibition. Furthermore, FHL2-KO SMCs showed
      enhanced migration compared with WT SMCs. In conclusion, FHL2 deficiency in mice
      results in exacerbated SMC-rich lesion formation involving increased
      proliferation and migration of SMCs via enhanced activation of the ERK1/2
      CyclinD1 signaling pathway. 

PMID- 24736600
TI  - Seasonal variation of dystocia in a large Danish cohort.
AB  - BACKGROUND: Dystocia is one of the most frequent causes of cesarean delivery in
      nulliparous women. Despite this, its causes are largely unknown. Vitamin D
      receptor (VDR) has been found in the myometrium. Thus, it is possible that
      vitamin D affects the contractility of the myometrium and may be involved in the
      pathogenesis of dystocia. Seasonal variation of dystocia in areas with distinct
      seasonal variation in sunlight exposure, like Denmark, could imply that vitamin D
      may play a role. This study examined whether there was seasonal variation in the
      incidence of dystocia in a Danish population. METHOD: We used information from a
      cohort of 34,261 nulliparous women with singleton pregnancies, spontaneous onset
      of labor between 37 and 42 completed gestational weeks, and vertex fetal
      presentation. All women gave birth between 1992 and 2010 at the Department of
      Obstetrics and Gynecology, Aarhus University Hospital, Skejby. Logistic
      regression combined with cubic spline was used to estimate the seasonal variation
      for each outcome after adjusting for calendar time. RESULTS: No evidence for
      seasonal variation was found for any of the outcomes: acute cesarean delivery due
      to dystocia (p = 0.44); instrumental vaginal delivery due to dystocia (p = 0.69);
      oxytocin augmentation due to dystocia (p = 0.46); and overall dystocia (p =
      0.91). CONCLUSION: No seasonal variation in the incidence of dystocia was
      observed in a large cohort of Danish women. This may reflect no association
      between vitamin D and dystocia, or alternatively that other factors with seasonal
      variation and influence on the occurrence of dystocia attenuate such an
      association.

PMID- 24736601
TI  - Usual interstitial pneumonia preceding collagen vascular disease: a retrospective
      case control study of patients initially diagnosed with idiopathic pulmonary
      fibrosis.
AB  - BACKGROUND: The aim of this study was to evaluate the cumulative incidence and
      the predictive factors for collagen vascular disease (CVD) in patients initially
      diagnosed with idiopathic pulmonary fibrosis (IPF), and to examine the features
      of patients who then developed CVD. METHODS: This was a retrospective review of
      111 consecutive patients with IPF diagnosed at our institution. None of the
      patients fulfilled any of the CVD criteria from the American College of
      Rheumatology (ACR) within 6 months or more after the diagnosis of IPF. RESULTS:
      Ten patients (9.0%) developed CVD during the follow-up period: four had
      rheumatoid arthritis (RA); four had microscopic polyangiitis (MPA); one had
      systemic sclerosis (SSc); and one had SSc and Sjogren's syndrome (SjS). The mean
      time until CVD diagnosis was 3.9 years. The cumulative incidences of CVD at 1, 5,
      and 10 years were 0.91%, 9.85%, and 15.5%, respectively. Patients who developed
      CVD were significantly younger, more likely to be women and had a better
      prognosis than those with IPF. Cox proportional hazards regression analysis
      showed that female sex and the presence of lymphoid aggregates with germinal
      centers were significantly associated with the occurrence of CVD in patients
      initially diagnosed with IPF. CONCLUSIONS: CVD is an important underlying
      condition in IPF, and shows better prognosis. The possibility of the development
      of CVD should remain a consideration in the follow-up of IPF.

PMID- 24736602
TI  - Tuning cell fate: from insights to vertebrate regeneration.
AB  - Epigenetic interventions are required to induce reprogramming from one cell type
      to another. At present, various cellular reprogramming methods such as somatic
      cell nuclear transfer, cell fusion, and direct reprogramming using transcription
      factors have been reported. In particular, direct reprogramming from somatic
      cells to induced pluripotent stem cells (iPSCs) has been achieved using defined
      factors that play important epigenetic roles. Although the mechanisms underlying
      cellular reprogramming and vertebrate regeneration, including appendage
      regeneration, remain unknown, dedifferentiation occurs at an early phase in both
      the events, and both events are contrasting with regard to cell death. We
      compared the current status of changes in cell fate of iPSCs with that of
      vertebrate regeneration and suggested that substantial insights into vertebrate
      regeneration should be helpful for safe applications of iPSCs to medicine. 

PMID- 24736604
TI  - Fusion of a xylan-binding module to gluco-oligosaccharide oxidase increases
      activity and promotes stable immobilization.
AB  - The xylan-binding module Clostridium thermocellum CBM22A was successfully fused
      to a gluco-oligosaccharide oxidase, GOOX-VN, from Sarocladium strictum via a
      short TP linker, allowing the fused protein to effectively bind different xylans.
      The presence of the CtCBM22A at the N-terminal of GOOX-VN increased catalytic
      activity on mono- and oligo-saccharides by 2-3 fold while not affecting binding
      affinity to these substrates. Notably, both GOOX-VN and its CBM fusion also
      showed oxidation of xylo-oligosaccharides with degrees of polymerization greater
      than six. Whereas fusion to CtCBM22A did not alter the thermostability of GOOX-VN
      or reduce substrate inhibition, CtCBM22A_GOOX-VN could be immobilized to
      insoluble oat spelt xylan while retaining wild-type activity. QCM-D analysis
      showed that the fused enzyme remained bound during oxidation. These features
      could be harnessed to generate hemicellulose-based biosensors that detect and
      quantify the presence of different oligosaccharides.

PMID- 24736605
TI  - CMT: a constrained multi-level thresholding approach for ChIP-Seq data analysis.
AB  - Genome-wide profiling of DNA-binding proteins using ChIP-Seq has emerged as an
      alternative to ChIP-chip methods. ChIP-Seq technology offers many advantages over
      ChIP-chip arrays, including but not limited to less noise, higher resolution, and
      more coverage. Several algorithms have been developed to take advantage of these
      abilities and find enriched regions by analyzing ChIP-Seq data. However, the
      complexity of analyzing various patterns of ChIP-Seq signals still needs the
      development of new algorithms. Most current algorithms use various heuristics to
      detect regions accurately. However, despite how many formulations are available,
      it is still difficult to accurately determine individual peaks corresponding to
      each binding event. We developed Constrained Multi-level Thresholding (CMT), an
      algorithm used to detect enriched regions on ChIP-Seq data. CMT employs a
      constraint-based module that can target regions within a specific range. We show
      that CMT has higher accuracy in detecting enriched regions (peaks) by objectively
      assessing its performance relative to other previously proposed peak finders.
      This is shown by testing three algorithms on the well-known FoxA1 Data set, four
      transcription factors (with a total of six antibodies) for Drosophila
      melanogaster and the H3K4ac antibody dataset. 

PMID- 24736606
TI  - Analysis of rare variants in the C3 gene in patients with age-related macular
      degeneration.
AB  - Age-related macular degeneration (AMD) is a progressive retinal disorder
      affecting over 33 million people worldwide. Genome-wide association studies
      (GWASs) for AMD identified common variants at 19 loci accounting for 15-65% of
      the heritability and it has been hypothesized that the missing heritability may
      be attributed to rare variants with large effect sizes. Common variants in the
      complement component 3 (C3) gene have been associated with AMD and recently a
      rare C3 variant (Lys155Gln) was identified which exerts a large effect on AMD
      susceptibility independent of the common variants. To explore whether additional
      rare variants in the C3 gene are associated with AMD, we sequenced all coding
      exons in 84 unrelated AMD cases. Subsequently, we genotyped all identified
      variants in 1474 AMD cases and 2258 controls. Additionally, because of the known
      genetic overlap between AMD and atypical hemolytic uremic syndrome (aHUS), we
      genotyped two recurrent aHUS-associated C3 mutations in the entire cohort.
      Overall, we identified three rare variants (Lys65Gln (P=0.04), Arg735Trp
      (OR=17.4, 95% CI=2.2-136; P=0.0003), and Ser1619Arg (OR=5.2, 95% CI=1.0-25;
      P=0.05) at the C3 locus that are associated with AMD in our EUGENDA cohort.
      However, the Arg735Trp and Ser1619Arg variants were not found to be associated
      with AMD in the Rotterdam Study. The Lys65Gln variant was only identified in
      patients from Nijmegen, the Netherlands, and thus may represent a region-specific
      AMD risk variant.

PMID- 24736608
TI  - 200 kHz commercial sonar systems generate lower frequency side lobes audible to
      some marine mammals.
AB  - The spectral properties of pulses transmitted by three commercially available 200
      kHz echo sounders were measured to assess the possibility that marine mammals
      might hear sound energy below the center (carrier) frequency that may be
      generated by transmitting short rectangular pulses. All three sounders were found
      to generate sound at frequencies below the center frequency and within the
      hearing range of some marine mammals, e.g. killer whales, false killer whales,
      beluga whales, Atlantic bottlenose dolphins, harbor porpoises, and others. The
      frequencies of these sub-harmonic sounds ranged from 90 to 130 kHz. These sounds
      were likely detectable by the animals over distances up to several hundred meters
      but were well below potentially harmful levels. The sounds generated by the
      sounders could potentially affect the behavior of marine mammals within fairly
      close proximity to the sources and therefore the exclusion of echo sounders from
      environmental impact analysis based solely on the center frequency output in
      relation to the range of marine mammal hearing should be reconsidered.

PMID- 24736607
TI  - A split-ubiquitin yeast two-hybrid screen to examine the substrate specificity of
      atToc159 and atToc132, two Arabidopsis chloroplast preprotein import receptors.
AB  - Post-translational import of nucleus-encoded chloroplast pre-proteins is critical
      for chloroplast biogenesis, and the Toc159 family of proteins serve as receptors
      for the process. Toc159 shares with other members of the family (e.g. Toc132),
      homologous GTPase (G-) and Membrane (M-) domains, but a highly dissimilar N
      terminal acidic (A-) domain. Although there is good evidence that atToc159 and
      atToc132 from Arabidopsis mediate the initial sorting step, preferentially
      recognizing photosynthetic and non-photosynthetic preproteins, respectively,
      relatively few chloroplast preproteins have been assigned as substrates for
      particular members of the Toc159 family, which has limited the proof for the
      hypothesis. The current study expands the number of known preprotein substrates
      for members of the Arabidopsis Toc159 receptor family using a split-ubiquitin
      membrane-based yeast two-hybrid system using the atToc159 G-domain (Toc159G),
      atToc132 G-domain (Toc132G) and atToc132 A- plus G-domains (Toc132AG) as baits.
      cDNA library screening with all three baits followed by pairwise interaction
      assays involving the 81 chloroplast preproteins identified show that although G
      domains of the Toc159 family are sufficient for preprotein recognition, they
      alone do not confer specificity for preprotein subclasses. The presence of the A
      domain fused to atToc132G (Toc132AG) not only positively influences its
      specificity for non-photosynthetic preproteins, but also negatively regulates the
      ability of this receptor to interact with a subset of photosynthetic preproteins.
      Our study not only substantiates the fact that atToc132 can serve as a receptor
      by directly binding to chloroplast preproteins but also proposes the existence of
      subsets of preproteins with different but overlapping affinities for more than
      one member of the Toc159 receptor family. 

PMID- 24736609
TI  - Homocysteine and carotid plaque stability: a cross-sectional study in Chinese
      adults.
AB  - BACKGROUND AND PURPOSE: This study aimed to explore the possible association of
      plasma total homocysteine with carotid plaque stability. METHODS: A cross
      sectional study was conducted from 2010 to 2011. A stratified random sample of
      2,919 Chinese participants aged 40 years or older was enrolled. Plasma total
      homocysteine levels were measured and carotid plaques were evaluated by
      ultrasonography. Logistic regression model was used to analyze the association of
      homocysteine levels to the progression of carotid plaque development, while
      adjusting for demographics and vascular risk factors. RESULTS: The mean level of
      plasma homocysteine in the subjects was 14.9 umol/l. Along with increase in
      homocysteine level, the risk of advanced carotid plaque elevated (odds ratio =
      1.28; 95% confidence interval = 1.09-1.51) after adjusting for age, sex, and
      other potential confounders. Stratified by sex, higher homocysteine level was
      strongly associated with advanced carotid plaque in men (OR = 1.41; 95%
      confidence interval = 1.17-1.70), but not in women. CONCLUSION: The findings
      suggest that plasma level of homocysteine may be associated with advanced carotid
      plaque, which constitutes high risks of stroke, in male Chinese adults.

PMID- 24736610
TI  - The performance of enhanced liver fibrosis (ELF) test for the staging of liver
      fibrosis: a meta-analysis.
AB  - BACKGROUND: The enhanced liver fibrosis test (ELF) has been shown to accurately
      predict significant liver fibrosis in several liver diseases. AIMS: To perform a
      meta-analysis to assess the performance of the ELF test for the assessment of
      liver fibrosis. STUDY: Electronic and manual searches were performed to identify
      studies of the ELF test. After methodological quality assessment and data
      extraction, pooled estimates of the sensitivity, specificity, area under the
      receiver operating characteristic curve (AUROC), positive likelihood ratio (PLR),
      negative likelihood ratio (NLR), diagnostic odds ratio (DOR) and summary receiver
      operating characteristics (sROC) were assessed systematically. The extent of
      heterogeneity and reasons for it were assessed. RESULTS: Nine studies were
      identified for analysis. The pooled sensitivity, specificity, positive LR,
      negative LR, and DOR values of ELF test, for assessment of significant liver
      fibrosis, were 83% (95% CI=0.80-0.86), 73% (95% CI=0.69-0.77), 4.00 (95% CI=2.50
      6.39), 0.24 (95% CI=0.17-0.34), and 16.10 (95% CI=8.27-31.34), respectively; and,
      for evaluation of severe liver fibrosis, were 78% (95% CI=0.74-0.81), 76% (95%
      CI=0.73-0.78), 4.39 (95% CI=2.76-6.97), 0.27 (95% CI=0.16-0.46), and 16.01 (95%
      CI: 7.15-35.82), respectively; and, for estimation of cirrhosis, were 80% (95%
      CI=0.75-0.85), 71% (95% CI=0.68-0.74), 3.13 (95% CI=2.01-4.87), 0.29 (95% CI=0.19
      0.44), and 14.09 (95% CI: 5.43-36.59), respectively. CONCLUSIONS: The ELF test
      shows good performance and considerable diagnostic value for the prediction of
      histological fibrosis stage.

PMID- 24736611
TI  - Increased migration of human mesenchymal stromal cells by autocrine motility
      factor (AMF) resulted in enhanced recruitment towards hepatocellular carcinoma.
AB  - BACKGROUND AND AIMS: Several reports described the migration of human mesenchymal
      stromal cells (MSCs) towards tumor-released factors. Autocrine motility factor
      (AMF) is produced by several tumors including hepatocellular carcinoma (HCC). The
      aim of this study was to analyze AMF involvement on MSC migration towards human
      HCC. METHODS: Production of AMF by HCC tumors was evaluated by western analysis.
      The effects of AMF on MSCs from different sources (bone marrow, adipose tissue
      and perivascular cells from umbilical cord) were analyzed using in vitro
      migration assay; metalloproteinase 2 (MMP2) activity and expression of critical
      genes were studied by zymography and qRT-PCR, respectively. To assess AMF
      involvement on the in vivo MSC migration, noninvasive fluorescence imaging was
      performed. To test the effect of AMF-primed MSCs on tumor development, in vitro
      proliferation and spheroids growth and in vivo tumor volume were evaluated.
      RESULTS: AMF produced by HCC was found to induce migration of different MSCs in
      vitro and to enhance their MMP2 activity. Stimulation of MSCs with recombinant
      AMF (rAMF) also induced the in vitro adhesion to endothelial cells in coincidence
      with changes in the expression levels of MMP3, AMF receptor, caveolin-1, and -2
      and GDI-2. Importantly, stimulation of MSCs with rAMF increased the in vivo
      migration of MSCs towards experimental HCC tumors. AMF-priming of MSCs did not
      induce a pro-tumorigenic effect on HCC cells neither in vivo nor in vitro.
      CONCLUSION: AMF plays a role in MSC recruitment towards HCC. However, its ability
      to increase MSC migration to HCC for therapeutic purposes merits further
      evaluation.

PMID- 24736612
TI  - Changes in the daily rhythm of lipid metabolism in the diabetic retina.
AB  - Disruption of circadian regulation was recently shown to cause diabetes and
      metabolic disease. We have previously demonstrated that retinal lipid metabolism
      contributed to the development of diabetic retinopathy. The goal of this study
      was to determine the effect of diabetes on circadian regulation of clock genes
      and lipid metabolism genes in the retina and retinal endothelial cells (REC).
      Diabetes had a pronounced inhibitory effect on the negative clock arm with lower
      amplitude of the period (per) 1 in the retina; lower amplitude and a phase shift
      of per2 in the liver; and a loss of cryptochrome (cry) 2 rhythmic pattern in
      suprachiasmatic nucleus (SCN). The positive clock arm was increased by diabetes
      with higher amplitude of circadian locomotor output cycles kaput (CLOCK) and
      brain and muscle aryl-hydrocarbon receptor nuclear translocator-like 1 (bmal1)
      and phase shift in bmal1 rhythmic oscillations in the retina; and higher bmal1
      amplitude in the SCN. Peroxisome proliferator-activated receptor (PPAR) alpha
      exhibited rhythmic oscillation in retina and liver; PPARgamma had lower amplitude
      in diabetic liver; sterol regulatory element-binding protein (srebp) 1c had
      higher amplitude in the retina but lower in the liver in STZ- induced diabetic
      animals. Both of Elongase (Elovl) 2 and Elovl4 had a rhythmic oscillation pattern
      in the control retina. Diabetic retinas lost Elovl4 rhythmic oscillation and had
      lower amplitude of Elovl2 oscillations. In line with the in vivo data, circadian
      expression levels of CLOCK, bmal1 and srebp1c had higher amplitude in rat REC
      (rREC) isolated from diabetic rats compared with control rats, while PPARgamma
      and Elovl2 had lower amplitude in diabetic rREC. In conclusion, diabetes causes
      dysregulation of circadian expression of clock genes and the genes controlling
      lipid metabolism in the retina with potential implications for the development of
      diabetic retinopathy. 

PMID- 24736613
TI  - Suicidality, bullying and other conduct and mental health correlates of traumatic
      brain injury in adolescents.
AB  - OBJECTIVE: Our knowledge on the adverse correlates of traumatic brain injuries
      (TBI), including non-hospitalized cases, among adolescents is limited to case
      studies. We report lifetime TBI and adverse mental health and conduct behaviours
      associated with TBI among adolescents from a population-based sample in Ontario.
      METHOD AND FINDINGS: Data were derived from 4,685 surveys administered to
      adolescents in grades 7 through 12 as part of the 2011 population-based cross
      sectional Ontario Student Drug Use and Health Survey (OSDUHS). Lifetime TBI was
      defined as head injury that resulted in being unconscious for at least 5 minutes
      or being retained in the hospital for at least one night, and was reported by
      19.5% (95%CI:17.3,21.9) of students. When holding constant sex, grade, and
      complex sample design, students with TBI had significantly greater odds of
      reporting elevated psychological distress (AOR = 1.52), attempting suicide (AOR =
      3.39), seeking counselling through a crisis help-line (AOR = 2.10), and being
      prescribed medication for anxiety, depression, or both (AOR = 2.45). Moreover,
      students with TBI had higher odds of being victimized through bullying at school
      (AOR = 1.70), being cyber-bullied (AOR = 2.05), and being threatened with a
      weapon at school (AOR = 2.90), compared with students who did not report TBI.
      Students with TBI also had higher odds of victimizing others and engaging in
      numerous violent as well as nonviolent conduct behaviours. CONCLUSIONS:
      Significant associations between TBI and adverse internalizing and externalizing
      behaviours were found in this large population-based study of adolescents. Those
      who reported lifetime TBI were at a high risk for experiencing mental and
      physical health harms in the past year than peers who never had a head injury.
      Primary physicians should be vigilant and screen for potential mental heath and
      behavioural harms in adolescent patients with TBI. Efforts to prevent TBI during
      adolescence and intervene at an early stage may reduce injuries and comorbid
      problems in this age group.

PMID- 24736614
TI  - Analysis of the salivary gland transcriptome of Frankliniella occidentalis.
AB  - Saliva is known to play a crucial role in insect feeding behavior and virus
      transmission. Currently, little is known about the salivary glands and saliva of
      thrips, despite the fact that Frankliniella occidentalis (Pergande) (the western
      flower thrips) is a serious pest due to its destructive feeding, wide host range,
      and transmission of tospoviruses. As a first step towards characterizing thrips
      salivary gland functions, we sequenced the transcriptome of the primary salivary
      glands of F. occidentalis using short read sequencing (Illumina) technology. A de
      novo-assembled transcriptome revealed 31,392 high quality contigs with an average
      size of 605 bp. A total of 12,166 contigs had significant BLASTx or tBLASTx hits
      (E<=1.0E-6) to known proteins, whereas a high percentage (61.24%) of contigs had
      no apparent protein or nucleotide hits. Comparison of the F. occidentalis
      salivary gland transcriptome (sialotranscriptome) against a published F.
      occidentalis full body transcriptome assembled from Roche-454 reads revealed
      several contigs with putative annotations associated with salivary gland
      functions. KEGG pathway analysis of the sialotranscriptome revealed that the
      majority (18 out of the top 20 predicted KEGG pathways) of the salivary gland
      contig sequences match proteins involved in metabolism. We identified several
      genes likely to be involved in detoxification and inhibition of plant defense
      responses including aldehyde dehydrogenase, metalloprotease, glucose oxidase,
      glucose dehydrogenase, and regucalcin. We also identified several genes that may
      play a role in the extra-oral digestion of plant structural tissues including
      beta-glucosidase and pectin lyase; and the extra-oral digestion of sugars,
      including alpha-amylase, maltase, sucrase, and alpha-glucosidase. This is the
      first analysis of a sialotranscriptome for any Thysanopteran species and it
      provides a foundational tool to further our understanding of how thrips interact
      with their plant hosts and the viruses they transmit. 

PMID- 24736616
TI  - A special issue in memoriam of Carl Woese.

PMID- 24736615
TI  - The HIV matrix protein p17 promotes the activation of human hepatic stellate
      cells through interactions with CXCR2 and Syndecan-2.
AB  - BACKGROUND: The human immunodeficiency virus type 1 (HIV-1) p17 is a matrix
      protein involved in virus life's cycle. CXCR2 and Syndecan-2, the two major
      coreceptors for the p17 protein, are expressed in hepatic stellate cells (HSCs),
      a key cell type involved in matrix deposition in liver fibrotic disorders. AIM:
      In this report we have investigated the in vitro impact of p17 on HSCs
      transdifferentiation and function and underlying signaling pathways involved in
      these processes. METHODS: LX-2 cells, a human HSC line, and primary HSC were
      challenged with p17 and expressions of fibrogenic markers and of p17 receptors
      were assessed by qRT-PCR and Western blot. Downstream intracellular signaling
      pathways were evaluated with qRT-PCR and Western blot as well as after pre
      treatment with specific pathway inhibitors. RESULTS: Exposure of LX2 cells to p17
      increases their contractile force, reshapes the cytoskeleton fibers and
      upregulates the expression of transdifferentiation markers including alphaSMA,
      COL1alpha1 and endothelin-1 through the activation of Jak/STAT and Rho signaling
      pathways. These effects are lost in HSCs pre-incubated with a serum from HIV
      positive person who underwent a vaccination with a p17 peptide. Confocal laser
      microscopy studies demonstrates that CXCR2 and syndecan-2 co-associate at the
      plasma membrane after exposure to p17. Immunostaining of HIV/HCV liver biopsies
      from co-infected patients reveals that the progression of liver fibrosis
      correlates with a reduced expression of CXCR2. CONCLUSIONS: The HIV matrix
      protein p17 is pro-fibrogenic through its interactions both with CXCR2 and
      syndecan-2 on activated HSCs.

PMID- 24736617
TI  - Introduction to special Carl Woese issue in RNA Biology.

PMID- 24736618
TI  - Carl Woese in Schenectady: the forgotten years.
AB  - Many of the authors of these short pieces (who were invited to contribute by
      Robin Gutell) have already written or spoken about Carl Woese since he died at
      the end of December 2012. My own thoughts were published in PNAS on February 26,
      2013. Still saddened by Carl's death, I re-read what I wrote at that moment. The
      article was OK, although it was not strong enough for what Carl taught us: he
      deserved better. I'd like us to admire what Carl did over 50 years (which is a
      given), and to admire even more the way he did it. While Carl's accomplishments
      were huge, his intense dedication to the ideas that consumed him was even more
      impressive. 

PMID- 24736619
TI  - Remembering Carl Woese.

PMID- 24736620
TI  - Systematic identification of cell-wall related genes in Populus based on analysis
      of functional modules in co-expression network.
AB  - The identification of novel genes relevant to plant cell wall (PCW) biosynthesis
      in Populus is a highly important and challenging problem. We surveyed candidate
      Populus cell wall genes using a non-targeted approach. First, a genome-wide
      Populus gene co-expression network (PGCN) was constructed using microarray data
      available in the public domain. Module detection was then performed, followed by
      gene ontology (GO) enrichment analysis, to assign the functional category to
      these modules. Based on GO annotation, the modules involved in PCW biosynthesis
      were then selected and analyzed in detail to annotate the candidate PCW genes in
      these modules, including gene annotation, expression of genes in different
      tissues, and so on. We examined the overrepresented cis-regulatory elements
      (CREs) in the gene promoters to understand the possible transcriptionally co
      regulated relationships among the genes within the functional modules of cell
      wall biosynthesis. PGCN contains 6,854 nodes (genes) with 324,238 edges. The
      topological properties of the network indicate scale-free and modular behavior. A
      total of 435 modules were identified; among which, 67 modules were identified by
      overrepresented GO terms. Six modules involved in cell wall biosynthesis were
      identified. Module 9 was mainly involved in cellular polysaccharide metabolic
      process in the primary cell wall, whereas Module 4 comprises genes involved in
      secondary cell wall biogenesis. In addition, we predicted and analyzed 10
      putative CREs in the promoters of the genes in Module 4 and Module 9. The non
      targeted approach of gene network analysis and the data presented here can help
      further identify and characterize cell wall related genes in Populus. 

PMID- 24736621
TI  - Risk adjustment for smoking identified through tobacco use diagnoses in hospital
      data: a validation study.
AB  - Adjustment for the differing risk profiles of patients is essential to the use of
      administrative hospital data for epidemiological research. Smoking is an
      important factor to include in such adjustments, but the accuracy of the
      diagnostic codes denoting smoking in hospital records is unknown. The aims of
      this study were to measure the validity of current smoking and ever smoked status
      identified from diagnoses in hospital records using a range of algorithms,
      relative to self-reported smoking status; and to examine whether the
      misclassification of smoking identified through hospital data is differential or
      non-differential with respect to common exposures and outcomes. Data from the
      baseline questionnaire of the 45 and Up Study, completed by 267,153 residents of
      New South Wales (NSW), Australia, aged 45 years and older, were linked to the NSW
      Admitted Patient Data Collection. Patients who had been admitted to hospital for
      an overnight stay between 1 July 2005 and the date of completion of the
      questionnaire (1 January 2006 to 2 March 2009) were included. Smokers were
      identified by applying a range of algorithms to hospital admission histories, and
      compared against self-reported smoking in the questionnaire ('gold standard').
      Sensitivities for current smoking ranged from 59% to 84%, while specificities
      were 94% to 98%. Sensitivities for ever smoked ranged from 45% to 74% and
      specificities were 93% to 97%. For the majority of algorithms, sensitivities
      and/or specificities differed significantly according to principal diagnosis,
      number of comorbidities, socioeconomic status, residential remoteness, Indigenous
      status, 28 day readmission and 365 day mortality. The identification of smoking
      through diagnoses in hospital data results in differential misclassification.
      Risk adjustment based on smoking identified from these data will yield
      potentially misleading results. Systematic capture of information about smoking
      in hospital records using a mandatory item would increase the utility of
      administrative data for epidemiological research. 

PMID- 24736622
TI  - Self-assembled ultrathin nanotubes on diamond (100) surface.
AB  - Surfaces of semiconductors are crucially important for electronics, especially
      when the devices are reduced to the nanoscale. However, surface structures are
      often elusive, impeding greatly the engineering of devices. Here we develop an
      efficient method that can automatically explore the surface structures using
      structure swarm intelligence. Its application to a simple diamond (100) surface
      reveals an unexpected surface reconstruction featuring self-assembled carbon
      nanotubes arrays. Such a surface is energetically competitive with the known
      dimer structure under normal conditions, but it becomes more favourable under a
      small compressive strain or at high temperatures. The intriguing covalent bonding
      between neighbouring tubes creates a unique feature of carrier kinetics (that is,
      one dimensionality of hole states, while two dimensionality of electron states)
      that could lead to novel design of superior electronics. Our findings highlight
      that the surface plays vital roles in the fabrication of nanodevices by being a
      functional part of them. 

PMID- 24736623
TI  - Developing capacities of community health workers in sexual and reproductive,
      maternal, newborn, child, and adolescent health: a mapping and review of training
      resources.
AB  - BACKGROUND: Given country demands for support in the training of community health
      workers (CHWs) to accelerate progress towards reaching the Millennium Development
      Goals in sexual and reproductive health and maternal, newborn, child, and
      adolescent health (SR/MNCAH), the United Nations Health Agencies conducted a
      synthesis of existing training resource packages for CHWs in different components
      of SR/MNCAH to identify gaps and opportunities and inform efforts to harmonize
      approaches to developing the capacity of CHWs. METHODS: A mapping of training
      resource packages for CHWs was undertaken with documents retrieved online and
      from key informants. Materials were classified by health themes and analysed
      using agreed parameters. Ways forward were informed by a subsequent expert
      consultation. RESULTS: We identified 31 relevant packages. They covered different
      components of the SR/MNCAH continuum in varying breadth (integrated packages) and
      depth (focused packages), including family planning, antenatal and childbirth
      care (mainly postpartum haemorrhage), newborn care, and childhood care, and HIV.
      There is no or limited coverage of interventions related to safe abortion,
      adolescent health, and gender-based violence. There is no training package
      addressing the range of evidence-based interventions that can be delivered by
      CHWs as per World Health Organization guidance. Gaps include weakness in the
      assessment of competencies of trainees, in supportive supervision, and in impact
      assessment of packages. Many packages represent individual programme efforts
      rather than national programme materials, which could reflect weak integration
      into national health systems. CONCLUSIONS: There is a wealth of training packages
      on SR/MNCAH for CHWs which reflects interest in strengthening the capacity of
      CHWs. This offers an opportunity for governments and partners to mount a
      synergistic response to address the gaps and ensure an evidence-based
      comprehensive package of interventions to be delivered by CHWs. Packages with
      defined competencies and methods for assessing competencies and supervision are
      considered best practices but remain a gap.

PMID- 24736624
TI  - Implicit learning of stimulus regularities increases cognitive control.
AB  - In this study we aim to examine how the implicit learning of statistical
      regularities of successive stimuli affects the ability to exert cognitive
      control. In three experiments, sequences of flanker stimuli were segregated into
      pairs, with the second stimulus contingent on the first. Response times were
      reliably faster for the second stimulus if its congruence tended to match the
      congruence of the preceding stimulus, even though most participants were not
      explicitly aware of the statistical regularities (Experiment 1). In contrast,
      performance was not enhanced if the congruence of the second stimuli tended to
      mismatch the congruence of the first stimulus (Experiment 2). The lack of
      improvement appears to result from a failure of learning mismatch contingencies
      (Experiment 3). The results suggest that implicit learning of inter-stimulus
      relationships can facilitate cognitive control. 

PMID- 24736625
TI  - Pou4f1 and pou4f2 are dispensable for the long-term survival of adult retinal
      ganglion cells in mice.
AB  - PURPOSE: To investigate the role of Pou4f1 and Pou4f2 in the survival of adult
      retinal ganglion cells (RGCs). METHODS: Conditional alleles of Pou4f1 and Pou4f2
      were generated (Pou4f1loxP and Pou4f2loxP respectively) for the removal of Pou4f1
      and Pou4f2 in adult retinas. A tamoxifen-inducible Cre was used to delete Pou4f1
      and Pou4f2 in adult mice and retinal sections and flat mounts were subjected to
      immunohistochemistry to confirm the deletion of both alleles and to quantify the
      changes in the number of RGCs and other retinal neurons. To determine the effect
      of loss of Pou4f1 and Pou4f2 on RGC survival after axonal injury, controlled
      optic nerve crush (CONC) was performed and RGC death was assessed. RESULTS:
      Pou4f1 and Pou4f2 were ablated two weeks after tamoxifen treatment. Retinal
      interneurons and Muller glial cells are not affected by the ablation of Pou4f1 or
      Pou4f2 or both. Although the deletion of both Pou4f1 and Pou4f2 slightly delays
      the death of RGCs at 3 days post-CONC in adult mice, it does not affect the cell
      death progress afterwards. Moreoever, deletion of Pou4f1 or Pou4f2 or both has no
      impact on the long-term viability of RGCs at up to 6 months post-tamoxifen
      treatment. CONCLUSION: Pou4f1 and Pou4f2 are involved in the acute response to
      damage to RGCs but are dispensable for the long-term survival of adult RGC in
      mice.

PMID- 24736626
TI  - Detecting falls as novelties in acceleration patterns acquired with smartphones.
AB  - Despite being a major public health problem, falls in the elderly cannot be
      detected efficiently yet. Many studies have used acceleration as the main input
      to discriminate between falls and activities of daily living (ADL). In recent
      years, there has been an increasing interest in using smartphones for fall
      detection. The most promising results have been obtained by supervised Machine
      Learning algorithms. However, a drawback of these approaches is that they rely on
      falls simulated by young or mature people, which might not represent every
      possible fall situation and might be different from older people's falls. Thus,
      we propose to tackle the problem of fall detection by applying a kind of novelty
      detection methods which rely only on true ADL. In this way, a fall is any
      abnormal movement with respect to ADL. A system based on these methods could
      easily adapt itself to new situations since new ADL could be recorded
      continuously and the system could be re-trained on the fly. The goal of this work
      is to explore the use of such novelty detectors by selecting one of them and by
      comparing it with a state-of-the-art traditional supervised method under
      different conditions. The data sets we have collected were recorded with
      smartphones. Ten volunteers simulated eight type of falls, whereas ADL were
      recorded while they carried the phone in their real life. Even though we have not
      collected data from the elderly, the data sets were suitable to check the
      adaptability of novelty detectors. They have been made publicly available to
      improve the reproducibility of our results. We have studied several novelty
      detection methods, selecting the nearest neighbour-based technique (NN) as the
      most suitable. Then, we have compared NN with the Support Vector Machine (SVM).
      In most situations a generic SVM outperformed an adapted NN. 

PMID- 24736627
TI  - A modified EpiSC culture condition containing a GSK3 inhibitor can support
      germline-competent pluripotency in mice.
AB  - Embryonic stem cells (ESCs) can contribute to the tissues of chimeric animals,
      including the germline. By contrast, epiblast stem cells (EpiSCs) barely
      contribute to chimeras. These two types of cells are established and maintained
      under different culture conditions. Here, we show that a modified EpiSC culture
      condition containing the GSK3 inhibitor CHIR99021 can support a germline
      competent pluripotent state that is intermediate between ESCs and EpiSCs. When
      ESCs were cultured under a modified condition containing bFGF, Activin A, and
      CHIR99021, they converted to intermediate pluripotent stem cells (INTPSCs). These
      INTPSCs were able to form teratomas in vivo and contribute to chimeras by
      blastocyst injection. We also induced formation of INTPSCs (iINTPSCs) from mouse
      embryonic fibroblasts by exogenous expression of four reprogramming factors,
      Oct3/4, Sox2, Klf4, and c-Myc, under the INTPSC culture condition. These iINTPSCs
      contributed efficiently to chimeras, including the germline, by blastocyst
      injection. The INTPSCs exhibited several characteristic properties of both ESCs
      and EpiSCs. Our results suggest that the modified EpiSC culture condition can
      support growth of cells that meet the most stringent criteria for pluripotency,
      and that germline-competent pluripotency may depend on the activation state of
      Wnt signaling.

PMID- 24736628
TI  - Efficacy and safety of lobeglitazone monotherapy in patients with type 2 diabetes
      mellitus over 24-weeks: a multicenter, randomized, double-blind, parallel-group,
      placebo controlled trial.
AB  - OBJECTIVE: The aim of this study was to assess the glucose-lowering and lipid
      modifying effects, and safety profile of lobeglitazone, a novel peroxisome
      proliferator-activated receptor- gamma agonist, compared to placebo as a
      monotherapy in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: In
      this 24-week, multicenter, randomized, double-blind, parallel-group, placebo
      controlled study, 173 patients were randomly assigned (a 2?1 ratio) to
      lobeglitazone 0.5 mg (n=115) or matching placebo (n=58) orally once daily. The
      primary endpoint was the change in glycated hemoglobin (HbA1c) from baseline to
      the end of treatment. The secondary endpoints included various glycemic
      parameters, lipid parameters and safety profile (ClinicalTrials.gov number
      NCT01001611). RESULTS: At 24 weeks, a significant reduction in HbA1c was observed
      with lobeglitazone versus placebo (-0.44% vs 0.16%, mean difference -0.6%,
      p<0.0001). The goal of HbA1c <7% was achieved significantly more in the
      lobeglitazone group compared to the placebo group (44% vs 12%, p<0.0001). Markers
      of insulin resistance were also improved in the lobeglitazone group. In addition,
      lobeglitazone treatment significantly improved triglycerides, high density
      lipoprotein cholesterol, small dense low density lipoprotein cholesterol, free
      fatty acid, and apolipoprotein-B/CIII compared to placebo (p<0.01, respectively).
      More weight gain was observed in the lobeglitazone group than the placebo group
      (0.89 kg vs - 0.63 kg, mean difference 1.52 kg, p<0.0001). The safety profile was
      comparable between the two groups and lobeglitazone was well tolerated.
      CONCLUSIONS: Lobeglitazone 0.5 mg showed a favorable balance in the efficacy and
      safety profile. The results support a potential role of lobeglitazone in treating
      type 2 diabetes. TRIAL REGISTRATION: Clinicaltrials.gov NCT01001611.

PMID- 24736630
TI  - In vitro metabolism of 20(R)-25-methoxyl-dammarane-3, 12, 20-triol from Panax
      notoginseng in human, monkey, dog, rat, and mouse liver microsomes.
AB  - The present study characterized in vitro metabolites of 20(R)-25-methoxyl
      dammarane-3beta, 12beta, 20-triol (20(R)-25-OCH3-PPD) in mouse, rat, dog, monkey
      and human liver microsomes. 20(R)-25-OCH3-PPD was incubated with liver microsomes
      in the presence of NADPH. The reaction mixtures and the metabolites were
      identified on the basis of their mass profiles using LC-Q/TOF and were quantified
      using triple quadrupole instrument by multiple reaction monitoring. A total of 7
      metabolites (M1-M7) of the phase I metabolites were detected in all species.
      25(R)-OCH3-PPD was metabolized by hydroxylation, dehydrogenation, and O
      demethylation. Enzyme kinetic of 20(R)-25-OCH3-PPD metabolism was evaluated in
      rat and human hepatic microsomes. Incubations studies with selective chemical
      inhibitors demonstrated that the metabolism of 20(R)-25-OCH3-PPD was primarily
      mediated by CYP3A4. We conclude that 20(R)-25-OCH3-PPD was metabolized
      extensively in mammalian species of mouse, rat, dog, monkey, and human. CYP3A4
      catalyzed oxygenation metabolism played an important role in the disposition of
      25(R)-OCH3-PPD, especially at the C-20 hydroxyl group. 

PMID- 24736629
TI  - L-arginine supplementation protects exercise performance and structural integrity
      of muscle fibers after a single bout of eccentric exercise in rats.
AB  - Eccentric exercise is known to disrupt sarcolemmal integrity and induce damage of
      skeletal muscle fibers. We hypothesized that L-arginine (L-Arg; nitric oxide
      synthase (NOS) substrate) supplementation prior to a single bout of eccentric
      exercise would diminish exercise-induced damage. In addition, we used N-nitro-L
      arginine methyl ester hydrochloride (L-NAME; NOS inhibitor) to clarify the role
      of native NOS activity in the development of exercise-induced muscle damage. Rats
      were divided into four groups: non-treated control (C), downhill running with
      (RA) or without (R) L-Arg supplementation and downhill running with L-NAME
      supplementation (RN). Twenty four hours following eccentric exercise seven rats
      in each group were sacrificed and soleus muscles were dissected and frozen for
      further analysis. The remaining seven rats in each group were subjected to the
      exercise performance test. Our experiments showed that L-Arg supplementation
      prior to a single bout of eccentric exercise improved subsequent exercise
      performance capacity tests in RA rats when compared with R, RN and C rats by 37%,
      27% and 13%, respectively. This outcome is mediated by L-Arg protection against
      post-exercise damage of sarcolemma (2.26- and 0.87-fold less than R and RN
      groups, respectively), reduced numbers of damaged muscle fibers indicated by the
      reduced loss of desmin content in the muscle (15% and 25% less than R and RN
      groups, respectively), and diminished u-calpain mRNA up-regulation (42% and 30%
      less than R and RN groups, respectively). In conclusion, our study indicates that
      L-Arg supplementation prior to a single bout of eccentric exercise alleviates
      muscle fiber damage and preserves exercise performance capacity. 

PMID- 24736631
TI  - Dll4-notch signalling blockade synergizes combined ultrasound-stimulated
      microbubble and radiation therapy in human colon cancer xenografts.
AB  - Tumour vasculature acts as an essential lifeline for tumour progression and
      facilitates metastatic spread. Novel vascular targeting strategies aiming to
      sustain vascular shutdown could potentially induce substantial damage, resulting
      in a significant tumour growth delay. We investigated the combination of two
      novel complementary vascular targeting agents with radiation therapy in a
      strategy aiming to sustain vascular disruption. Experiments were carried out with
      delta-like ligand 4 (Dll4) blockade (angiogenesis deregulator) treatment
      administered in combination with a radiation-based vascular destruction treatment
      in a highly aggressive well-perfused colon cancer tumour line implanted in female
      athymic nude mice. Tumours were treated with permutations of radiation,
      ultrasound-stimulated microbubbles (USMB) and Dll4 monoclonal antibody (mAb).
      Tumour vascular response was assessed with three-dimensional power Doppler
      ultrasound to measure active flow and immunohistochemistry. Tumour response was
      assessed with histochemical assays and longitudinal measurements of tumour
      volume. Our results suggest a significant tumour response in animals treated with
      USMB combined with radiation, and Dll4 mAb, leading to a synergistic tumour
      growth delay of up to 24 days. This is likely linked to rapid cell death within
      the tumour and a sustained tumour vascular shutdown. We conclude that the triple
      combination treatments cause a vascular shutdown followed by a sustained
      inhibition of angiogenesis and tumour cell death, leading to a rapid tumour
      vascular-based 'collapse' and a significant tumour growth delay. 

PMID- 24736632
TI  - A clinicopathological study of early-stage synchronous bilateral breast cancer: a
      retrospective evaluation and prospective validation of potential risk factors.
AB  - BACKGROUND: The aim of the present study was to investigate potential risk
      factors for synchronous bilateral breast cancer sBBC). METHODS: A retrospective
      analysis was performed of patients diagnosed and treated with operable bilateral
      breast cancer (BBC) between June 2007 and December 2011. Risk factors for sBBC
      were evaluated in this cohort and further validated in a prospective
      observational validation analysis of patients between January 2012 and December
      2012. Patients treated with operable unilateral breast cancer during the same
      period were used as a control group. RESULTS: A total of 11,247 patients with
      primary breast cancer underwent operations at the Fudan University Shanghai
      Cancer Center between June 2007 and December 2012. The incidence of sBBC was
      1.6%. The age at diagnosis (HR = 2.4, 95% C.I.: 1.4-4.0, p = 0.001), presence of
      sclerosing adenosis (HR = 11.8, 95% C.I.: 5.3-26.3, p<0.001), lobular carcinoma
      component involvement (HR = 5.6, 95% C.I.: 2.6-12.1, p<0.001), and family history
      of first-degree relatives with breast cancer (HR = 2.0, 95% C.I.: 1.1-3.4,
      p<0.001) were independent risk factors for sBBC. A subsequent validation study
      failed to confirm the significance of family history. No significant difference
      on survival was found between patients with early-stage sBBC and control cases.
      CONCLUSIONS: Patients with the presence of sclerosing in the affected breast, and
      lobular carcinoma component involvement may be at high risk for developing sBBC.
      This study supports the hypothesis that the host-carcinoma biological
      relationship, especially for the tumor microenvironment, played a critical role
      in the carcinogenesis of sBBC.

PMID- 24736633
TI  - The impacts of read length and transcriptome complexity for de novo assembly: a
      simulation study.
AB  - Transcriptome assembly using RNA-seq data - particularly in non-model organisms
      has been dramatically improved, but only recently have the pre-assembly
      procedures, such as sequencing depth and error correction, been studied.
      Increasing read length is viewed as a crucial condition to further improve
      transcriptome assembly, but it is unknown whether the read length really matters.
      In addition, though many assembly tools are available now, it is unclear whether
      the existing assemblers perform well enough for all data with different
      transcriptome complexities. In this paper, we studied these two open problems
      using two high-performing assemblers, Velvet/Oases and Trinity, on several
      simulated datasets of human, mouse and S.cerevisiae. The results suggest that (1)
      the read length of paired reads does not matter once it exceeds a certain
      threshold, and interestingly, the threshold is distinct in different organisms;
      (2) the quality of de novo assembly decreases sharply with the increase of
      transcriptome complexity, all existing de novo assemblers tend to corrupt
      whenever the genes contain a large number of alternative splicing events. 

PMID- 24736634
TI  - Identification of the immunodominant regions of Staphylococcus aureus fibronectin
      binding protein A.
AB  - Staphylococcus aureus is an opportunistic bacterial pathogen responsible for a
      diverse spectrum of human diseases and a leading cause of nosocomial and
      community-acquired infections. Development of a vaccine against this pathogen is
      an important goal. The fibronectin binding protein A (FnBPA) of S. aureus is one
      of multifunctional 'microbial surface components recognizing adhesive matrix
      molecules' (MSCRAMMs). It is one of the most important adhesin molecules involved
      in the initial adhesion steps of S. aureus infection. It has been studied as
      potential vaccine candidates. However, FnBPA is a high-molecular-weight protein
      of 106 kDa and difficulties in achieving its high-level expression in vitro limit
      its vaccine application in S. aureus infection diseases control. Therefore,
      mapping the immunodominant regions of FnBPA is important for developing
      polyvalent subunit fusion vaccines against S. aureus infections. In the present
      study, we cloned and expressed the N-terminal and C-terminal of FnBPA. We
      evaluated the immunogenicity of the two sections of FnBPA and the protective
      efficacy of the two truncated fragments vaccines in a murine model of systemic S.
      aureus infection. The results showed recombinant truncated fragment F130-500 had
      a strong immunogenicity property and survival rates significantly increased in
      the group of mice immunized with F130-500 than the control group. We futher
      identified the immunodominant regions of FnBPA. The mouse antisera reactions
      suggest that the region covering residues 110 to 263 (F1B110-263) is highly
      immunogenic and is the immunodominant regions of FnBPA. Moreover, vaccination
      with F1B110-263 can generate partial protection against lethal challenge with two
      different S. aureus strains and reduced bacterial burdens against non-lethal
      challenge as well as that immunization with F130-500. This information will be
      important for further developing anti- S. aureus polyvalent subunit fusion
      vaccines. 

PMID- 24736636
TI  - Identifying and overcoming obstacles in angiogenic gene therapy for myocardial
      ischemia.
AB  - Well-developed coronary collateral vessels in patients with symptomatic coronary
      artery disease were shown to be associated with reduced future cardiovascular
      morbidity and mortality. However, the majority of patients with coronary artery
      disease lack adequate functional coronary collateral circulation. Stimulation of
      collateral vessel development by angiogenic growth factor therapy (therapeutic
      angiogenesis) has been tested in many clinical trials in the past, but the
      potential of this new treatment paradigm has not been realized yet in late stage
      clinical trials. Mechanistic insights into collateral vessel development and the
      collective clinical experience in the past decade identified specific obstacles
      that might have impeded the progress in the field. This review identifies some of
      the key conceptual, technical, and clinical hurdles and recommends strategies to
      overcome them in future clinical trials.

PMID- 24736635
TI  - The pro-inflammatory cytokine, interleukin-6, enhances the polarization of
      alternatively activated macrophages.
AB  - Macrophages are important innate immune cells that are associated with two
      distinct phenotypes: a pro-inflammatory (or classically activated) subset with
      prototypic macrophage functions such as inflammatory cytokine production and
      bactericidal activity, and an anti-inflammatory (or alternatively activated
      (AAM)) subset linked with wound healing and tissue repair processes. In this
      study, we examined the effect of interlukein-6 on human and murine macrophage
      polarization. The results indicate that despite being commonly associated with
      pro-inflammatory functions and being implicated in the
      pathogenesis/pathophysiology of numerous inflammatory diseases, interleukin-6 can
      enhance the polarization of AAMs, based on increased expression of hallmark
      markers: arginase-1, Ym1 and CD206; this effect required the AAM differentiating
      cytokines, IL-4 and IL-13. Co-treatment of AAMs with IL-6 resulted in spontaneous
      release of IL-10, suppressed LPS-induced nitric oxide production and inhibited
      cytokine production by activated CD4+ T cells - immunoregulatory features not
      observed in the 'parent' IL-4+IL-13-induced AAM. The effect of IL-6 required
      signal transducer and activator of transcription (STAT)-3, was partially
      dependent on up-regulation of the IL4Ralpha chain, and was independent of
      autocrine IL-10. In the presence of IFNgamma, IL-6 promoted the production of IL
      1beta and TNFalpha suggesting that this cytokine can enhance the phenotype to
      which a macrophage has committed. This finding may explain the pleiotrophic
      nature of IL-6, where it is associated with the perpetuation and enhancement of
      disease in inflammatory situations, but is also necessary for resolution of
      inflammation and adequate wound healing to occur in others. Thus, the potential
      benefit of IL-6 in promoting an AAM, with its' anti-inflammatory and wound
      healing ability, may need to be considered in immunotherapies aimed at in vivo
      modulation or inhibition of IL-6. 

PMID- 24736637
TI  - Dual antiplatelet therapy after drug-eluting stent implantation: when is "enough"
      enough?

PMID- 24736639
TI  - Evolutionary dynamics in the southwest Indian ocean marine biodiversity hotspot:
      a perspective from the rocky shore gastropod genus Nerita.
AB  - The Southwest Indian Ocean (SWIO) is a striking marine biodiversity hotspot.
      Coral reefs in this region host a high proportion of endemics compared to total
      species richness and they are particularly threatened by human activities. The
      island archipelagos with their diverse marine habitats constitute a natural
      laboratory for studying diversification processes. Rocky shores in the SWIO
      region have remained understudied. This habitat presents a high diversity of
      molluscs, in particular gastropods. To explore the role of climatic and
      geological factors in lineage diversification within the genus Nerita, we
      constructed a new phylogeny with an associated chronogram from two mitochondrial
      genes [cytochrome oxidase sub-unit 1 and 16S rRNA], combining previously
      published and new data from eight species sampled throughout the region. All
      species from the SWIO originated less than 20 Ma ago, their closest extant
      relatives living in the Indo-Australian Archipelago (IAA). Furthermore, the SWIO
      clades within species with Indo-Pacific distribution ranges are quite recent,
      less than 5 Ma. These results suggest that the regional diversification of Nerita
      is closely linked to tectonic events in the SWIO region. The Reunion mantle plume
      head reached Earth's surface 67 Ma and has been stable and active since then,
      generating island archipelagos, some of which are partly below sea level today.
      Since the Miocene, sea-level fluctuations have intermittently created new rocky
      shore habitats. These represent ephemeral stepping-stones, which have likely
      facilitated repeated colonization by intertidal gastropods, like Nerita
      populations from the IAA, leading to allopatric speciation. This highlights the
      importance of taking into account past climatic and geological factors when
      studying diversification of highly dispersive tropical marine species. It also
      underlines the unique history of the marine biodiversity of the SWIO region. 

PMID- 24736640
TI  - Correlative tomography.
AB  - Increasingly researchers are looking to bring together perspectives across
      multiple scales, or to combine insights from different techniques, for the same
      region of interest. To this end, correlative microscopy has already yielded
      substantial new insights in two dimensions (2D). Here we develop correlative
      tomography where the correlative task is somewhat more challenging because the
      volume of interest is typically hidden beneath the sample surface. We have
      threaded together x-ray computed tomography, serial section FIB-SEM tomography,
      electron backscatter diffraction and finally TEM elemental analysis all for the
      same 3D region. This has allowed observation of the competition between pitting
      corrosion and intergranular corrosion at multiple scales revealing the structural
      hierarchy, crystallography and chemistry of veiled corrosion pits in stainless
      steel. With automated correlative workflows and co-visualization of the multi
      scale or multi-modal datasets the technique promises to provide insights across
      biological, geological and materials science that are impossible using either
      individual or multiple uncorrelated techniques. 

PMID- 24736641
TI  - A novel wild-type Saccharomyces cerevisiae strain TSH1 in scaling-up of solid
      state fermentation of ethanol from sweet sorghum stalks.
AB  - The rising demand for bioethanol, the most common alternative to petroleum
      derived fuel used worldwide, has encouraged a feedstock shift to non-food crops
      to reduce the competition for resources between food and energy production. Sweet
      sorghum has become one of the most promising non-food energy crops because of its
      high output and strong adaptive ability. However, the means by which sweet
      sorghum stalks can be cost-effectively utilized for ethanol fermentation in large
      scale industrial production and commercialization remains unclear. In this study,
      we identified a novel Saccharomyces cerevisiae strain, TSH1, from the soil in
      which sweet sorghum stalks were stored. This strain exhibited excellent ethanol
      fermentative capacity and ability to withstand stressful solid-state fermentation
      conditions. Furthermore, we gradually scaled up from a 500-mL flask to a 127-m3
      rotary-drum fermenter and eventually constructed a 550-m3 rotary-drum
      fermentation system to establish an efficient industrial fermentation platform
      based on TSH1. The batch fermentations were completed in less than 20 hours, with
      up to 96 tons of crushed sweet sorghum stalks in the 550-m3 fermenter reaching
      88% of relative theoretical ethanol yield (RTEY). These results collectively
      demonstrate that ethanol solid-state fermentation technology can be a highly
      efficient and low-cost solution for utilizing sweet sorghum, providing a feasible
      and economical means of developing non-food bioethanol. 

PMID- 24736643
TI  - An activist doctor joins the electoral fray in Rajasthan.

PMID- 24736642
TI  - Major and minor group rhinoviruses elicit differential signaling and cytokine
      responses as a function of receptor-mediated signal transduction.
AB  - Major- and minor-group human rhinoviruses (HRV) enter their host by binding to
      the cell surface molecules ICAM-1 and LDL-R, respectively, which are present on
      both macrophages and epithelial cells. Although epithelial cells are the primary
      site of productive HRV infection, previous studies have implicated macrophages in
      establishing the cytokine dysregulation that occurs during rhinovirus-induced
      asthma exacerbations. Analysis of the transcriptome of primary human macrophages
      exposed to major- and minor-group HRV demonstrated differential gene expression.
      Alterations in gene expression were traced to differential mitochondrial activity
      and signaling pathway activation between two rhinovirus serotypes, HRV16 (major
      group) and HRV1A (minor-group), upon initial HRV binding. Variances in
      phosphorylation of kinases (p38, JNK, ERK5) and transcription factors (ATF-2,
      CREB, CEBP-alpha) were observed between the major- and minor-group HRV
      treatments. Differential activation of signaling pathways led to changes in the
      production of the asthma-relevant cytokines CCL20, CCL2, and IL-10. This is the
      first report of genetically similar viruses eliciting dissimilar cytokine
      release, transcription factor phosphorylation, and MAPK activation from
      macrophages, suggesting that receptor use is a mechanism for establishing the
      inflammatory microenvironment in the human airway upon exposure to rhinovirus. 

PMID- 24736644
TI  - Supplementing exposure to hypoxia with a copper depleted diet does not exacerbate
      right ventricular remodeling in mice.
AB  - BACKGROUND: Pulmonary hypertension and subsequent right ventricular (RV) failure
      are associated with high morbidity and mortality. Prognosis is determined by
      occurrence of RV failure. Currently, adequate treatment for RV failure is
      lacking. Further research into the molecular basis for the development of RV
      failure as well as the development of better murine models of RV failure are
      therefore imperative. We hypothesize that adding a low-copper diet to chronic
      hypoxia in mice reinforces their individual effect and that the combination of
      mild pulmonary vascular remodeling and capillary rarefaction, induces RV failure.
      METHODS: Six week old mice were subjected to normoxia (N; 21% O2) or hypoxia (H;
      10% O2) during a period of 8 weeks and received either a normal diet (Cu+) or a
      copper depleted diet (Cu-). Cardiac function was assessed by echocardiography and
      MRI analysis. RESULTS AND CONCLUSION: Here, we characterized a mouse model of
      chronic hypoxia combined with a copper depleted diet and demonstrate that eight
      weeks of chronic hypoxia (10%) is sufficient to induce RV hypertrophy and
      subsequent RV failure. Addition of a low copper diet to hypoxia did not have any
      further deleterious effects on right ventricular remodeling.

PMID- 24736645
TI  - Isolation and characterization of broad spectrum coaggregating bacteria from
      different water systems for potential use in bioaugmentation.
AB  - The bridging bacteria with broad-spectrum coaggregation ability play an important
      role during multispecies-biofilm development. In this study, through a visual and
      semi-quantitative assay, twenty-two bacterial strains with aggregation ability
      were obtained from 8 different water environments, and these strains were
      assigned to 7 genera according to their 16S rDNA and they were Aeromonas,
      Bacillus, Comamonas, Exiguobacterium, Pseudomonas, Shewanella and Comamonas.
      Furthermore, all possible 231 pairwise combinations among these 22 strains were
      explored for coaggregation ability by spectrophotometric assay. Among all these
      strains, it was found that Bacillus cereus G5 and Bacillus megaterium T1
      coaggregated with themajority of assayed other strains, 90.5% (19 of 21 strains)
      and 76.2% respectively (17 of 21 strains) at a higher coaggregation rates (A.I.
      greater than 50%), indicating they have a broad-spectrum coaggregation property.
      The images of coaggregates also confirmed the coexistence of G5 and T1 with their
      partner strains. Biofilm biomass development of G5 cocultured with each of its
      partner strains were further evaluateded. The results showed that 15 of 21
      strains, when paired with G5, developed greater biofilm biomass than the
      monocultures. Furthermore, the images from both fluorescence microscopy and
      scanning electron microscopy (SEM) demonstrated that G5 and A3-GFP (a 3,5
      dinitrobenzoic acid-degrading strain, staining with gfp),could develop a typical
      spatial structure of dual-species biofilm when cocultured. These results
      suggested that bridging-bacteria with a broad spectrum coaggregating ability,
      such as G5,could mediate the integration of exogenous degrading bacteria into
      biofilms and contribute to the bioaugmentation treatment. 

PMID- 24736646
TI  - Effects of hypocretin/orexin cell transplantation on narcoleptic-like sleep
      behavior in rats.
AB  - The sleep disorder narcolepsy is now considered a neurodegenerative disease
      because there is a massive loss of neurons containing the neuropeptide
      hypocretin/orexin (HCRT). In consequence, narcoleptic patients have very low
      cerebrospinal fluid (CSF) levels of HCRT. Studies in animal models of narcolepsy
      have shown the neurophysiological role of the HCRT system in the development of
      this disease. For example, the injection of the neurotoxin named hypocretin-2
      saporin (HCRT2/SAP) into the lateral hypothalamus (LH) destroys the HCRT neurons,
      therefore diminishes the contents of HCRT in the CSF and induces narcoleptic-like
      behavior in rats. Transplants of various cell types have been used to induce
      recovery in a variety of neurodegenerative animal models. In models such as
      Parkinson's disease, cell survival has been shown to be small but satisfactory.
      Similarly, cell transplantation could be employed to implant grafts of HCRT cells
      into the LH or even other brain regions to treat narcolepsy. Here, we report for
      the first time that transplantation of HCRT neurons into the LH of HCRT2/SAP
      lesioned rats diminishes narcoleptic-like sleep behavior. Therefore, cell
      transplantation may provide an effective method to treat narcolepsy. 

PMID- 24736647
TI  - Generation and dietary modulation of anti-inflammatory electrophilic omega-3
      fatty acid derivatives.
AB  - Dietary omega-3 polyunsaturated fatty acids (PUFAs) decrease cardiovascular risk
      via suppression of inflammation. The generation of electrophilic alpha,beta
      unsaturated ketone derivatives of the omega-3 PUFAs docosahexaenoic acid (DHA)
      and docosapentaenoic acid (DPA) in activated human macrophages is catalyzed by
      cyclooxygenase-2 (Cox-2). These derivatives are potent pleiotropic anti
      inflammatory signaling mediators that act via mechanisms including the activation
      of Nrf2-dependent phase 2 gene expression and suppression of pro-inflammatory NF
      kappaB-driven gene expression. Herein, the endogenous generation of omega-3 PUFAs
      electrophilic ketone derivatives and their hydroxy precursors was evaluated in
      human neutrophils. In addition, their dietary modulation was assessed through a
      randomized clinical trial. METHODS: Endogenous generation of electrophilic omega
      3 PUFAs and their hydroxy precursors was evaluated by mass spectrometry in
      neutrophils isolated from healthy subjects, both at baseline and upon stimulation
      with calcium ionophore. For the clinical trial, participants were healthy adults
      30-55 years of age with a reported EPA+DHA consumption of <=300 mg/day randomly
      assigned to parallel groups receiving daily oil capsule supplements for a period
      of 4 months containing either 1.4 g of EPA+DHA (active condition, n = 24) or
      identical appearing soybean oil (control condition, n = 21). Participants and
      laboratory technicians remained blinded to treatment assignments. RESULTS: 5
      lypoxygenase-dependent endogenous generation of 7-oxo-DHA, 7-oxo-DPA and 5-oxo
      EPA and their hydroxy precursors is reported in human neutrophils stimulated with
      calcium ionophore and phorbol 12-myristate 13-acetate (PMA). Dietary EPA+DHA
      supplementation significantly increased the formation of 7-oxo-DHA and 5-oxo-EPA,
      with no significant modulation of arachidonic acid (AA) metabolite levels.
      CONCLUSIONS: The endogenous detection of these electrophilic omega-3 fatty acid
      ketone derivatives supports the precept that the benefit of omega-3 PUFA-rich
      diets can be attributed to the generation of electrophilic oxygenated metabolites
      that transduce anti-inflammatory actions rather than the suppression of pro
      inflammatory AA metabolites. TRIAL REGISTRATION: ClinicalTrials.gov NCT00663871.

PMID- 24736648
TI  - Exopolysaccharides isolated from hydrothermal vent bacteria can modulate the
      complement system.
AB  - The complement system is involved in the defence against bacterial infection, or
      in the elimination of tumour cells. However, disturbances in this system
      contributes to the pathogenesis of various inflammatory diseases. The efficiency
      of therapeutic anti-tumour antibodies is enhanced when the complement system is
      stimulated. In contrast, cancer cells are able to inhibit the complement system
      and thus proliferate. Some marine molecules are currently being developed as new
      drugs for use in humans. Among them, known exopolyssacharides (EPSs) generally
      originate from fungi, but few studies have been performed on bacterial EPSs and
      even fewer on EPSs extracted from deep-sea hydrothermal vent microbes. For use in
      humans, these high molecular weight EPSs must be depolymerised. Furthermore, the
      over-sulphation of EPSs can modify their biological activity. The aim of this
      study was to investigate the immunodulation of the complement system by either
      native or over-sulphated low molecular weight EPSs isolated from vent bacteria in
      order to find pro or anti-activators of complement. 

PMID- 24736649
TI  - Rotavirus increases levels of lipidated LC3 supporting accumulation of infectious
      progeny virus without inducing autophagosome formation.
AB  - Replication of many RNA viruses benefits from subversion of the autophagic
      pathway through many different mechanisms. Rotavirus, the main etiologic agent of
      pediatric gastroenteritis worldwide, has been recently described to induce
      accumulation of autophagosomes as a mean for targeting viral proteins to the
      sites of viral replication. Here we show that the viral-induced increase of the
      lipidated form of LC3 does not correlate with an augmented formation of
      autophagosomes, as detected by immunofluorescence and electron microscopy. The
      LC3-II accumulation was found to be dependent on active rotavirus replication
      through the use of antigenically intact inactivated viral particles and of siRNAs
      targeting viral genes that are essential for viral replication. Silencing
      expression of LC3 or of Atg7, a protein involved in LC3 lipidation, resulted in a
      significant impairment of viral titers, indicating that these elements of the
      autophagic pathway are required at late stages of the viral cycle.

PMID- 24736650
TI  - The relationships between foot arch volumes and dynamic plantar pressure during
      midstance of walking in preschool children.
AB  - OBJECTIVES: The purpose of this study was to examine the correlation between the
      foot arch volume measured from static positions and the plantar pressure
      distribution during walking. METHODS: A total of 27 children, two to six years of
      age, were included in this study. Measurements of static foot posture were
      obtained, including navicular height and foot arch volume in sitting and standing
      positions. Plantar pressure, force and contact areas under ten different regions
      of the foot were obtained during walking. RESULTS: The foot arch index was
      correlated (r = 0.32) with the pressure difference under the midfoot during the
      foot flat phase. The navicular heights and foot arch volumes in sitting and
      standing positions were correlated with the mean forces and pressures under the
      first (r = -0.296~-0.355) and second metatarsals (r = -0.335~-0.504) and midfoot
      (r = -0.331~-0.496) during the stance phase of walking. The contact areas under
      the foot were correlated with the foot arch parameters, except for the area under
      the midfoot. CONCLUSIONS: The foot arch index measured in a static position could
      be a functional index to predict the dynamic foot functions when walking. The
      foot arch is a factor which will influence the pressure distribution under the
      foot. Children with a lower foot arch demonstrated higher mean pressure and force
      under the medial forefoot and midfoot, and lower contact areas under the foot,
      except for the midfoot region. Therefore, children with flatfoot may shift their
      body weight to a more medial foot position when walking, and could be at a higher
      risk of soft tissue injury in this area.

PMID- 24736651
TI  - MP3: a software tool for the prediction of pathogenic proteins in genomic and
      metagenomic data.
AB  - The identification of virulent proteins in any de-novo sequenced genome is useful
      in estimating its pathogenic ability and understanding the mechanism of
      pathogenesis. Similarly, the identification of such proteins could be valuable in
      comparing the metagenome of healthy and diseased individuals and estimating the
      proportion of pathogenic species. However, the common challenge in both the above
      tasks is the identification of virulent proteins since a significant proportion
      of genomic and metagenomic proteins are novel and yet unannotated. The currently
      available tools which carry out the identification of virulent proteins provide
      limited accuracy and cannot be used on large datasets. Therefore, we have
      developed an MP3 standalone tool and web server for the prediction of pathogenic
      proteins in both genomic and metagenomic datasets. MP3 is developed using an
      integrated Support Vector Machine (SVM) and Hidden Markov Model (HMM) approach to
      carry out highly fast, sensitive and accurate prediction of pathogenic proteins.
      It displayed Sensitivity, Specificity, MCC and accuracy values of 92%, 100%, 0.92
      and 96%, respectively, on blind dataset constructed using complete proteins. On
      the two metagenomic blind datasets (Blind A: 51-100 amino acids and Blind B: 30
      50 amino acids), it displayed Sensitivity, Specificity, MCC and accuracy values
      of 82.39%, 97.86%, 0.80 and 89.32% for Blind A and 71.60%, 94.48%, 0.67 and
      81.86% for Blind B, respectively. In addition, the performance of MP3 was
      validated on selected bacterial genomic and real metagenomic datasets. To our
      knowledge, MP3 is the only program that specializes in fast and accurate
      identification of partial pathogenic proteins predicted from short (100-150 bp)
      metagenomic reads and also performs exceptionally well on complete protein
      sequences. MP3 is publicly available at
      http://metagenomics.iiserb.ac.in/mp3/index.php. 

PMID- 24736652
TI  - Distant homology modeling of LCAT and its validation through in silico targeting
      and in vitro and in vivo assays.
AB  - LCAT (lecithin:cholesterol acyltransferase) catalyzes the transacylation of a
      fatty acid of lecithin to cholesterol, generating a cholesteryl ester and
      lysolecithin. The knowledge of LCAT atomic structure and the identification of
      the amino acids relevant in controlling its structure and function are expected
      to be very helpful to understand the enzyme catalytic mechanism, as involved in
      HDL cholesterol metabolism. However - after an early report in the late '90 s -
      no recent advance has been made about LCAT three-dimensional structure. In this
      paper, we propose an LCAT atomistic model, built following the most up-to-date
      molecular modeling approaches, and exploiting newly solved crystallographic
      structures. LCAT shows the typical folding of the alpha/beta hydrolase
      superfamily, and its topology is characterized by a combination of alpha-helices
      covering a central 7-strand beta-sheet. LCAT presents a Ser/Asp/His catalytic
      triad with a peculiar geometry, which is shared with such other enzyme classes as
      lipases, proteases and esterases. Our proposed model was validated through
      different approaches. We evaluated the impact on LCAT structure of some point
      mutations close to the enzyme active site (Lys218Asn, Thr274Ala, Thr274Ile) and
      explained, at a molecular level, their phenotypic effects. Furthermore, we
      devised some LCAT modulators either designed through a de novo strategy or
      identified through a virtual high-throughput screening pipeline. The tested
      compounds were proven to be potent inhibitors of the enzyme activity. 

PMID- 24736653
TI  - HIV risk perception and behavior among sex workers in three major urban centers
      of Mozambique.
AB  - HIV risk perceptions and behaviors of 236 commercial sex workers from three major
      Mozambican urban centers were studied using the International Rapid Assessment,
      Response and Evaluation (I-RARE) methodology. All were offered HIV testing and,
      in Maputo, syphilis testing was offered as well. Sixty-three of the 236 opted for
      HIV testing, with 30 (48%) testing positive for HIV. In Maputo, all 30 receiving
      HIV tests also had syphilis testing, with 6 (20%) found to be positive. Results
      include interview excerpts and qualitative results using I-RARE methodology and
      AnSWR-assisted analyses of the interviews and focus group sessions. 

PMID- 24736654
TI  - The ovine cerebral venous system: comparative anatomy, visualization, and
      implications for translational research.
AB  - Cerebrovascular diseases are significant causes of death and disability in
      humans. Improvements in diagnostic and therapeutic approaches strongly rely on
      adequate gyrencephalic, large animal models being demanded for translational
      research. Ovine stroke models may represent a promising approach but are
      currently limited by insufficient knowledge regarding the venous system of the
      cerebral angioarchitecture. The present study was intended to provide a
      comprehensive anatomical analysis of the intracranial venous system in sheep as a
      reliable basis for the interpretation of experimental results in such ovine
      models. We used corrosion casts as well as contrast-enhanced magnetic resonance
      venography to scrutinize blood drainage from the brain. This combined approach
      yielded detailed and, to some extent, novel findings. In particular, we provide
      evidence for chordae Willisii and lateral venous lacunae, and report on
      connections between the dorsal and ventral sinuses in this species. For the first
      time, we also describe venous confluences in the deep cerebral venous system and
      an 'anterior condylar confluent' as seen in humans. This report provides a
      detailed reference for the interpretation of venous diagnostic imaging findings
      in sheep, including an assessment of structure detectability by in vivo (imaging)
      versus ex vivo (corrosion cast) visualization methods. Moreover, it features a
      comprehensive interspecies-comparison of the venous cerebral angioarchitecture in
      man, rodents, canines and sheep as a relevant large animal model species, and
      describes possible implications for translational cerebrovascular research. 

PMID- 24736659
TI  - Decomposition of organic carbon in fine soil particles is likely more sensitive
      to warming than in coarse particles: an incubation study with temperate grassland
      and forest soils in northern China.
AB  - It is widely recognized that global warming promotes soil organic carbon (SOC)
      decomposition, and soils thus emit more CO2 into the atmosphere because of the
      warming; however, the response of SOC decomposition to this warming in different
      soil textures is unclear. This lack of knowledge limits our projection of SOC
      turnover and CO2 emission from soils after future warming. To investigate the CO2
      emission from soils with different textures, we conducted a 107-day incubation
      experiment. The soils were sampled from temperate forest and grassland in
      northern China. The incubation was conducted over three short-term cycles of
      changing temperature from 5 degrees C to 30 degrees C, with an interval of 5
      degrees C. Our results indicated that CO2 emissions from sand (>50 um), silt (2
      50 um), and clay (<2 um) particles increased exponentially with increasing
      temperature. The sand fractions emitted more CO2 (CO2-C per unit fraction-C) than
      the silt and clay fractions in both forest and grassland soils. The temperature
      sensitivity of the CO2 emission from soil particles, which is expressed as Q10,
      decreased in the order clay>silt>sand. Our study also found that nitrogen
      availability in the soil facilitated the temperature dependence of SOC
      decomposition. A further analysis of the incubation data indicated a power-law
      decrease of Q10 with increasing temperature. Our results suggested that the
      decomposition of organic carbon in fine-textured soils that are rich in clay or
      silt could be more sensitive to warming than those in coarse sandy soils and that
      SOC might be more vulnerable in boreal and temperate regions than in subtropical
      and tropical regions under future warming.

PMID- 24736658
TI  - Expression of a truncated ATHB17 protein in maize increases ear weight at
      silking.
AB  - ATHB17 (AT2G01430) is an Arabidopsis gene encoding a member of the alpha-subclass
      of the homeodomain leucine zipper class II (HD-Zip II) family of transcription
      factors. The ATHB17 monomer contains four domains common to all class II HD-Zip
      proteins: a putative repression domain adjacent to a homeodomain, leucine zipper,
      and carboxy terminal domain. However, it also possesses a unique N-terminus not
      present in other members of the family. In this study we demonstrate that the
      unique 73 amino acid N-terminus is involved in regulation of cellular
      localization of ATHB17. The ATHB17 protein is shown to function as a
      transcriptional repressor and an EAR-like motif is identified within the putative
      repression domain of ATHB17. Transformation of maize with an ATHB17 expression
      construct leads to the expression of ATHB17Delta113, a truncated protein lacking
      the first 113 amino acids which encodes a significant portion of the repression
      domain. Because ATHB17Delta113 lacks the repression domain, the protein cannot
      directly affect the transcription of its target genes. ATHB17Delta113 can
      homodimerize, form heterodimers with maize endogenous HD-Zip II proteins, and
      bind to target DNA sequences; thus, ATHB17Delta113 may interfere with HD-Zip II
      mediated transcriptional activity via a dominant negative mechanism. We provide
      evidence that maize HD-Zip II proteins function as transcriptional repressors and
      that ATHB17Delta113 relieves this HD-Zip II mediated transcriptional repression
      activity. Expression of ATHB17Delta113 in maize leads to increased ear size at
      silking and, therefore, may enhance sink potential. We hypothesize that this
      phenotype could be a result of modulation of endogenous HD-Zip II pathways in
      maize. 

PMID- 24736660
TI  - Patterns of biomass and carbon distribution across a chronosequence of Chinese
      pine (Pinus tabulaeformis) forests.
AB  - Patterns of biomass and carbon (C) storage distribution across Chinese pine
      (Pinus tabulaeformis) natural secondary forests are poorly documented. The
      objectives of this study were to examine the biomass and C pools of the major
      ecosystem components in a replicated age sequence of P. tabulaeformis secondary
      forest stands in Northern China. Within each stand, biomass of above- and
      belowground tree, understory (shrub and herb), and forest floor were determined
      from plot-level investigation and destructive sampling. Allometric equations
      using the diameter at breast height (DBH) were developed to quantify plant
      biomass. C stocks in the tree and understory biomass, forest floor, and mineral
      soil (0-100 cm) were estimated by analyzing the C concentration of each
      component. The results showed that the tree biomass of P. tabulaeformis stands
      was ranged from 123.8 Mg.ha-1 for the young stand to 344.8 Mg.ha-1 for the mature
      stand. The understory biomass ranged from 1.8 Mg.ha-1 in the middle-aged stand to
      3.5 Mg.ha-1 in the young stand. Forest floor biomass increased steady with stand
      age, ranging from 14.9 to 23.0 Mg.ha-1. The highest mean C concentration across
      the chronosequence was found in tree branch while the lowest mean C concentration
      was found in forest floor. The observed C stock of the aboveground tree, shrub,
      forest floor, and mineral soil increased with increasing stand age, whereas the
      herb C stock showed a decreasing trend with a sigmoid pattern. The C stock of
      forest ecosystem in young, middle-aged, immature, and mature stands were 178.1,
      236.3, 297.7, and 359.8 Mg C ha-1, respectively, greater than those under similar
      aged P. tabulaeformis forests in China. These results are likely to be integrated
      into further forest management plans and generalized in other contexts to
      evaluate C stocks at the regional scale. 

PMID- 24736661
TI  - Control of established colon cancer xenografts using a novel humanized single
      chain antibody-streptococcal superantigen fusion protein targeting the 5T4
      oncofetal antigen.
AB  - Superantigens (SAgs) are microbial toxins that cross-link T cell receptors with
      major histocompatibility class II (MHC-II) molecules leading to the activation of
      large numbers of T cells. Herein, we describe the development and preclinical
      testing of a novel tumor-targeted SAg (TTS) therapeutic built using the
      streptococcal pyrogenic exotoxin C (SpeC) SAg and targeting cancer cells
      expressing the 5T4 tumor-associated antigen (TAA). To inhibit potentially harmful
      widespread immune cell activation, a SpeC mutation within the high-affinity MHC
      II binding interface was generated (SpeCD203A) that demonstrated a pronounced
      reduction in mitogenic activity, yet this mutant could still induce immune cell
      mediated cancer cell death in vitro. To target 5T4+ cancer cells, we engineered a
      humanized single chain variable fragment (scFv) antibody to recognize 5T4
      (scFv5T4). Specific targeting of scFv5T4 was verified. SpeCD203A fused to scFv5T4
      maintained the ability to activate and induce immune cell-mediated cytotoxicity
      of colorectal cancer cells. Using a xenograft model of established human colon
      cancer, we demonstrated that the SpeC-based TTS was able to control the growth
      and spread of large tumors in vivo. This required both TAA targeting by scFv5T4
      and functional SAg activity. These studies lay the foundation for the development
      of streptococcal SAgs as 'next-generation' TTSs for cancer immunotherapy. 

PMID- 24736662
TI  - Enhancement mechanisms of graphene in nano-58S bioactive glass scaffold:
      mechanical and biological performance.
AB  - Graphene is a novel material and currently popular as an enabler for the next
      generation nanocomposites. Here, we report the use of graphene to improve the
      mechanical properties of nano-58S bioactive glass for bone repair and
      regeneration. And the composite scaffolds were fabricated by a homemade selective
      laser sintering system. Qualitative and quantitative analysis demonstrated the
      successful incorporation of graphene into the scaffold without obvious structural
      damage and weight loss. The optimum compressive strength and fracture toughness
      reached 48.65 +/- 3.19 MPa and 1.94 +/- 0.10 MPa . m(1/2) with graphene content
      of 0.5 wt%, indicating significant improvements by 105% and 38% respectively. The
      mechanisms of pull-out, crack bridging, crack deflection and crack tip shielding
      were found to be responsible for the mechanical enhancement. Simulated body fluid
      and cell culture tests indicated favorable bioactivity and biocompatibility of
      the composite scaffold. The results suggest a great potential of graphene/nano
      58S composite scaffold for bone tissue engineering applications.

PMID- 24736664
TI  - Validation of type 2 diabetes risk variants identified by genome-wide association
      studies in Han Chinese population: a replication study and meta-analysis.
AB  - BACKGROUND: Several genome-wide association studies (GWAS) involving European
      populations have successfully identified risk genetic variants associated with
      type 2 diabetes mellitus (T2DM). However, the effects conferred by these variants
      in Han Chinese population have not yet been fully elucidated. METHODS: We
      analyzed the effects of 24 risk genetic variants with reported associations from
      European GWAS in 3,040 Han Chinese subjects in Taiwan (including 1,520 T2DM cases
      and 1,520 controls). The discriminative power of the prediction models with and
      without genotype scores was compared. We further meta-analyzed the association of
      these variants with T2DM by pooling all candidate-gene association studies
      conducted in Han Chinese. RESULTS: Five risk variants in IGF2BP2 (rs4402960,
      rs1470579), CDKAL1 (rs10946398), SLC30A8 (rs13266634), and HHEX (rs1111875) genes
      were nominally associated with T2DM in our samples. The odds ratio was 2.22 (95%
      confidence interval, 1.81-2.73, P<0.0001) for subjects with the highest genetic
      score quartile (score>34) as compared with subjects with the lowest quartile
      (score<29). The incoporation of genotype score into the predictive model
      increased the C-statistics from 0.627 to 0.657 (P<0.0001). These estimates are
      very close to those observed in European populations. Gene-environment
      interaction analysis showed a significant interaction between rs13266634 in
      SLC30A8 gene and age on T2DM risk (P<0.0001). Further meta-analysis pooling 20
      studies in Han Chinese confirmed the association of 10 genetic variants in
      IGF2BP2, CDKAL1, JAZF1, SCL30A8, HHEX, TCF7L2, EXT2, and FTO genes with T2DM. The
      effect sizes conferred by these risk variants in Han Chinese were similar to
      those observed in Europeans but the allele frequencies differ substantially
      between two populations. CONCLUSION: We confirmed the association of 10 variants
      identified by European GWAS with T2DM in Han Chinese population. The
      incorporation of genotype scores into the prediction model led to a small but
      significant improvement in T2DM prediction.

PMID- 24736663
TI  - The TrkAIII oncoprotein inhibits mitochondrial free radical ROS-induced death of
      SH-SY5Y neuroblastoma cells by augmenting SOD2 expression and activity at the
      mitochondria, within the context of a tumour stem cell-like phenotype.
AB  - The developmental and stress-regulated alternative TrkAIII splice variant of the
      NGF receptor TrkA is expressed by advanced stage human neuroblastomas (NBs),
      correlates with worse outcome in high TrkA expressing unfavourable tumours and
      exhibits oncogenic activity in NB models. In the present study, we report that
      constitutive TrkAIII expression in human SH-SY5Y NB cells inhibits Rotenone,
      Paraquat and LY83583-induced mitochondrial free radical reactive oxygen species
      (ROS)-mediated death by stimulating SOD2 expression, increasing mitochondrial
      SOD2 activity and attenuating mitochondrial free radical ROS production, in
      association with increased mitochondrial capacity to produce H2O2, within the
      context of a more tumour stem cell-like phenotype. This effect can be reversed by
      the specific TrkA tyrosine kinase inhibitor GW441756, by the multi-kinase TrkA
      inhibitors K252a, CEP-701 and Go6976, which inhibit SOD2 expression, and by siRNA
      knockdown of SOD2 expression, which restores the sensitivity of TrkAIII
      expressing SH-SY5Y cells to Rotenone, Paraquat and LY83583-induced mitochondrial
      free radical ROS production and ROS-mediated death. The data implicate the novel
      TrkAIII/SOD2 axis in promoting NB resistance to mitochondrial free radical
      mediated death and staminality, and suggest that the combined use of TrkAIII
      and/or SOD2 inhibitors together with agents that induce mitochondrial free
      radical ROS-mediated death could provide a therapeutic advantage that may also
      target the stem cell niche in high TrkA expressing unfavourable NB. 

PMID- 24736665
TI  - Autobiographical thinking interferes with episodic memory consolidation.
AB  - New episodic memories are retained better if learning is followed by a few
      minutes of wakeful rest than by the encoding of novel external information. Novel
      encoding is said to interfere with the consolidation of recently acquired
      episodic memories. Here we report four experiments in which we examined whether
      autobiographical thinking, i.e. an 'internal' memory activity, also interferes
      with episodic memory consolidation. Participants were presented with three
      wordlists consisting of common nouns; one list was followed by wakeful rest, one
      by novel picture encoding and one by autobiographical retrieval/future
      imagination, cued by concrete sounds. Both novel encoding and autobiographical
      retrieval/future imagination lowered wordlist retention significantly. Follow-up
      experiments demonstrated that the interference by our cued autobiographical
      retrieval/future imagination delay condition could not be accounted for by the
      sound cues alone or by executive retrieval processes. Moreover, our results
      demonstrated evidence of a temporal gradient of interference across experiments.
      Thus, we propose that rich autobiographical retrieval/future imagination hampers
      the consolidation of recently acquired episodic memories and that such
      interference is particularly likely in the presence of external concrete cues. 

PMID- 24736666
TI  - Length-dependent thermal conductivity in suspended single-layer graphene.
AB  - Graphene exhibits extraordinary electronic and mechanical properties, and
      extremely high thermal conductivity. Being a very stable atomically thick
      membrane that can be suspended between two leads, graphene provides a perfect
      test platform for studying thermal conductivity in two-dimensional systems, which
      is of primary importance for phonon transport in low-dimensional materials. Here
      we report experimental measurements and non-equilibrium molecular dynamics
      simulations of thermal conduction in suspended single-layer graphene as a
      function of both temperature and sample length. Interestingly and in contrast to
      bulk materials, at 300 K, thermal conductivity keeps increasing and remains
      logarithmically divergent with sample length even for sample lengths much larger
      than the average phonon mean free path. This result is a consequence of the two
      dimensional nature of phonons in graphene, and provides fundamental understanding
      of thermal transport in two-dimensional materials.

PMID- 24736667
TI  - Intradermal spitz nevi: a rare subtype of spitz nevi analyzed in a
      clinicopathologic study of 74 cases.
AB  - Spitz nevi are acquired melanocytic lesions with a wide histomorphological
      spectrum; reliable distinction from spitzoid melanoma is often difficult.
      Misdiagnoses of benign spitzoid tumors as spitzoid melanomas and vice versa are
      attributable to a frequently disturbing morphology and inconsistent or poorly
      defined histological criteria for diagnosis. Many recognized histological
      variants of Spitz nevi have been described, including the intradermal Spitz.
      Histopathologic descriptions of intradermal Spitz nevi have been done in the
      past; however, large studies addressing their histological spectrum have been
      lacking. We have retrospectively assessed the morphological features in 74 cases
      of intradermal Spitz nevi, excluding tumors clearly defined as atypical Spitz
      nevi and Spitzoid melanomas, to further delineate their histological spectrum.
      The patients' ages ranged from 5 to 81 years (median: 27). Anatomic location
      included: the upper extremities (27 cases), followed by head and neck (22 cases),
      lower extremities (9 cases), back (8 cases), buttock (5 cases), chest (1 case),
      and vulva (1 case). In 1 case, the anatomic location of the lesion was not
      available. Different histological variants were observed including hyalinized,
      polypoid, desmoplastic, angiomatoid, and halo Spitz. Morphological features
      evaluated included symmetry (100%), cell type (epithelioid 42%, spindle 16%,
      mixed 42%), maturation (85%), pigmentation (26%), chronic inflammation (24%), and
      mitotic activity (38%). Mild atypia was seen in 36 cases (49%), moderate atypia
      was seen in 28 cases (38%), and severe atypia was seen in 10 cases (14%).
      Intradermal Spitz nevus is a distinctive type of Spitz nevus that sometimes can
      be difficult to define given the unusual features that these lesions can show;
      thus, strict application of well-defined histological criteria and awareness of
      their morphological spectrum will facilitate definitive diagnosis.

PMID- 24736668
TI  - Pruritic keratotic plaque in the natal cleft.

PMID- 24736669
TI  - The significance of Melan-A-positive pagetoid melanocytosis in dysplastic nevi.
AB  - Dysplastic nevi may occasionally display alarming histological features. One of
      these features is the presence of upward spread of melanocytes (pagetoid
      melanocytosis), identified either on routine histologic sections or after
      immunohistochemistry using one of the melanocytic markers. Forty-three cases of
      dysplastic nevi with mild to moderate atypia were selected and retrieved, and
      Melan-A staining was performed. Melan-A-positive cells with pagetoid architecture
      were present in 27 cases (63%). Of these, only 5 cases demonstrated pagetoid
      architecture on routine staining. It is concluded that Melan-A staining should be
      used only with caution as an adjunct to routine histology in the evaluation of
      dysplastic nevi with mild to moderate atypia because the identification of
      pagetoid melanocytosis using this technique has the potential to lead to an
      erroneous diagnosis of melanoma.

PMID- 24736671
TI  - Localized chronic fibrosing vasculitis in a tattoo: a unique adverse tattoo
      reaction.
AB  - Decorative tattoos are associated with a variety of adverse cutaneous reactions.
      We describe a unique fibrosing vasculitic reaction to red tattoo ink. The
      histopathology was similar to that in localized chronic fibrosing vasculitis
      (LCFV), but sharply limited to sites of red tattoo ink injection and associated
      with florid verrucoid epidermal hyperplasia. LCFV has been described in a broad
      variety of slowly progressive disorders with a firm consistency such as erythema
      elevatum diutinum, plasma cell granuloma, granuloma faciale, and IgG4-associated
      sclerosing diseases. It has been hypothesized that LCFV is the result of
      maladaptive immune reaction with failure to clear the causative antigen. To the
      best of our knowledge, this is the first case of LCFV associated with tattoo. We
      speculate on the implications our case holds for the pathogenesis of LCFV.

PMID- 24736672
TI  - Desmoplastic primitive nonneural granular cell tumor of the skin.
AB  - Primitive nonneural granular cell tumor of the skin was first described by LeBoit
      et al in 1991 as "primitive polypoid granular cell tumor." Few cases have been
      reported to date, all being polypoid or deep well-delimited lesions and formed by
      large spindle or polygonal granular cells with moderate nuclear atypia and
      increased mitotic activity. This granular cell population does not have a
      Schwannian, myogenic, melanocytic, fibroblastic, histiocytic, or epithelial
      differentiation. We report a case that fully satisfies the criteria for primitive
      nonneural granular cell tumor of the skin and, in addition, shows an extensive
      desmoplastic stroma. This desmoplastic variant of primitive nonneural granular
      cell tumor, which to our knowledge has not been previously reported, should be
      recognized to appropriately face the differential diagnosis with the malignant
      granular cell tumor, whose criteria for malignancy cannot be applied to primitive
      granular cell tumors.

PMID- 24736673
TI  - Theoretical investigation of the borazine-melamine polymer as a novel candidate
      for hydrogen storage applications.
AB  - Ab initio calculations and molecular dynamic simulation were employed to study
      the interaction of molecular hydrogen with the borazine-melamine polymer (BMP) in
      order to explore its potential for hydrogen storage applications. The
      calculations were performed using the long range corrected version of density
      functional theory, the Coulomb-attenuating method (CAM-B3LYP) and the second
      order Moller-Plesset perturbation theory (MP2). The results showed that the
      average adsorption energy per hydrogen is about -0.7 and -0.3 kcal mol(-1) at the
      MP2/6-311+G(d,p) and CAMB3LYP/6-311+G(d,p) levels of theory, respectively. The
      adsorption energies were corrected for the basis set superposition error (BSSE)
      by the counterpoise method. It was found that the hydrogen storage capacity of
      the BMP is about 6.49 wt%, which is close to the values reported for the other
      selected materials for the hydrogen storage in the literature. The maximum number
      of hydrogen molecules, which were adsorbed by the BMP building block, is about
      ten. Molecular dynamic simulation was performed to assess the potential of BMP
      for hydrogen storage. 

PMID- 24736674
TI  - Post-synthetic metalation of metal-organic frameworks.
AB  - Post-synthetic metalation (PSMet) offers expansive scope for a targeted approach
      to tailoring the properties of MOFs. Numerous methods for carrying-out PSMet
      chemistry have been reported, however, these can be categorized into three
      general strategies: (a) addition to coordinating groups; (b) counter-ion exchange
      in charged frameworks; or, (c) host-guest encapsulation of metal-containing
      entities within the pores of the framework. PSMet has been applied to enhance the
      performance characteristics of parent MOFs for gas storage and separation, and
      catalysis. Notably, PSMet is a prominent strategy in the field of MOF catalysis
      as it offers a route to design size-selective catalysts, based on the premise of
      reticular chemistry in MOFs and the ability to incorporate a range of
      catalytically-active metal centres. Other applications for materials produced via
      or utilising PSMet strategies include enhancing gas storage or molecular
      separations, the triggered release of drugs, sensing and tunable light emission
      for luminescent materials. This review surveys seminal examples of PSMet to
      highlight the broad scope of this technique for enhancing the performance
      characteristics of MOFs and to demonstrate how the PSMet concept can be developed
      for future applications. 

PMID- 24736675
TI  - Complexation of DNA with ruthenium organometallic compounds: the high
      complexation ratio limit.
AB  - Interactions between DNA and ruthenium organometallic compounds are studied by
      using visible light absorption and circular dichroism measurements. A titration
      technique allowing for the absolute determination of the advancement degree of
      the complexation, without any assumption about the number of complexation modes
      is developed. When DNA is in excess, complexation involves intercalation of one
      of the organometallic compound ligands between DNA base pairs. But, in the high
      complexation ratio limit, where organometallic compounds are in excess relative
      to the DNA base pairs, a new mode of interaction is observed, in which the
      organometallic compound interacts weakly with DNA. The weak interaction mode,
      moreover, develops when all the DNA intercalation sites are occupied. A regime is
      reached in which one DNA base pair is linked to more than one organometallic
      compound. 

PMID- 24736676
TI  - Task-specific and general cognitive effects in Chiari malformation type I.
AB  - OBJECTIVE: Our objective was to use episodic memory and executive function tests
      to determine whether or not Chiari Malformation Type I (CM) patients experience
      cognitive dysfunction. BACKGROUND: CM is a neurological syndrome in which the
      cerebellum descends into the cervical spine causing neural compression, severe
      headaches, neck pain, and number of other physical symptoms. While primarily a
      disorder of the cervico-medullary junction, both clinicians and researchers have
      suspected deficits in higher-level cognitive function. DESIGN AND METHODS: We
      tested 24 CM patients who had undergone decompression neurosurgery and 24 age-
      and education-matched controls on measures of immediate and delayed episodic
      memory, as well as three measures of executive function. RESULTS: The CM group
      showed performance decrements relative to the controls in response inhibition
      (Stroop interference), working memory computational speed (Ospan), and processing
      speed (automated digit symbol substitution task), but group differences in recall
      did not reach statistical significance. After statistical control for depression
      and anxiety scores, the group effects for working memory and processing speed
      were eliminated, but not for response inhibition. This response inhibition
      difference was not due to overall general slowing for the CM group, either,
      because when controls' data were transformed using the linear function fit to all
      of the reaction time tasks, the interaction with group remained statistically
      significant. Furthermore, there was a multivariate group effect for all of the
      response time measures and immediate and delayed recall after statistical control
      of depression and anxiety scores. CONCLUSION: These results suggest that CM
      patients with decompression surgery exhibit cognitive dysfunction compared to age
      and education-matched controls. While some of these results may be related to
      anxiety and depression (likely proxies for chronic pain), response inhibition
      effects, in particular, as well as a general cognitive deficit persisted even
      after control for anxiety and decompression.

PMID- 24736677
TI  - Preventing vitamin B12 deficiency in South Asian women of childbearing age: a
      randomised controlled trial comparing an oral vitamin B12 supplement with B12
      dietary advice.
AB  - BACKGROUND/OBJECTIVES: To examine the effectiveness, acceptability and
      sustainability of interventions to reduce vitamin B12 (B12) deficiency in South
      Asian women before conception. SUBJECTS/METHODS: A 6-month randomised controlled
      trial conducted in Auckland, New Zealand. Participants (62 South Asian women, 18
      50 years old) were stratified by dietary practices, then randomised to three
      treatment groups: B12 Supplement (oral cyanocobalamin 6 MUg/day) (n=21), Placebo
      (n=21), or B12 Dietary Advice (n=20). Primary outcome measures were changes in
      B12 biomarkers (serum B12 and holotranscobalamin (holoTC)) at 6 months. Dietary
      B12 intake was estimated from a B12 food-specific frequency questionnaire
      (B12FFQ). Intention-to-treat analysis was applied using 'last observation carried
      forward' method. Changes in B12 biomarkers by treatment were compared using
      analysis of variance. Pearson's correlations tested relationships between dietary
      B12 intake and B12 biomarkers. RESULTS: At baseline, 48% of women tested as
      insufficient or deficient in serum B12 (<222 pmol/l) and 51% as insufficient or
      deficient in holoTC (<45 pmol/l). B12 status was moderately correlated with
      dietary B12 intake (r=0.5, 95% confidence interval (CI) (0.3-0.7)) and 44% of
      women reported insufficient dietary intake (<2.4 MUg/day). B12 Supplement was the
      only treatment group to record a significant increase in B12 biomarkers over 6
      months: serum B12 by 30% (95% CI (11-48%)) and holoTC by 42% (12-72%).
      CONCLUSIONS: The prevalence of B12 insufficiency among Auckland South Asian women
      is high and moderately correlated with inadequate intake of foods that contain
      B12. Cyanocobalamin supplementation (6 MUg/day) was associated with improved B12
      biomarkers, with a potential to improve preconception B12 status in South Asian
      women.

PMID- 24736678
TI  - Comparison of breast milk vitamin A concentration measured in fresh milk by a
      rapid field assay (the iCheck FLUORO) with standard measurement of stored milk by
      HPLC.
AB  - Availability of rapid, point-of-contact analytical methods would facilitate the
      use of breast milk vitamin A concentration (BMVA) to assess vitamin A (VA)
      status. We compared BMVA concentrations measured by high-performance liquid
      chromatography (HPLC) (the standard technique) with those by iCheck FLUORO, a new
      portable fluorometer that can rapidly quantify BMVA. Casual breast milk samples
      (n=154) were collected during a representative survey in Yaounde and Douala,
      Cameroon. Milk fat and BMVA concentrations (by iCheck) were measured in fresh
      milk in the field. After storage at <-20  degrees C, BMVA concentrations were
      also measured by HPLC. BMVA values from the two methods were highly correlated
      (R(2)=0.72 for BMVA/l; R(2)=0.62 for BMVA/g fat, both P<0.0001). HPLC values were
      greater than iCheck values on average, and the difference increased with
      increasing BMVA. The iCheck FLUORO could be useful for monitoring fortification
      programs, but before-after surveys to assess change in BMVA concentrations should
      use one method consistently. 

PMID- 24736679
TI  - Impact of stearic acid and oleic acid on hemostatic factors in the context of
      controlled diets consumed by healthy men.
AB  - The effects of stearic acid (STA) on cardiovascular disease risk beyond lipid and
      lipoprotein risk factors, including hemostasis, are unclear, particularly when
      compared with unsaturated fatty acids. The aim of the present study is to compare
      the effects of STA with those of oleic acid (OL) on markers of hemostasis. In a
      randomized crossover study, 50 men consumed six controlled diets for 5 weeks each
      (39% energy from fat, 15% energy from protein, 46% energy from carbohydrate
      (CHO)). Fat (8% energy) was replaced across diets by: STA, OL, CHO (control),
      trans fatty acids (TFAs), TFA/STA and 12:0-16:0 saturated fatty acids. Factor
      VIIc, plasminogen activator inhibitor-1 (PAI-1) and plasmin alpha-2-antiplasmin
      complex concentrations were not different between OL and STA (P>0.05). Compared
      with control, OL increased factor VIIc and PAI-1 (P<=0.05), whereas there were no
      differences with STA (P>0.05). STA and OL similarly affect markers of hemostasis
      in healthy men, within the context of a highly controlled diet.

PMID- 24736680
TI  - Seasonal differences in total antioxidant capacity intake from foods consumed by
      a Japanese population.
AB  - BACKGROUND/OBJECTIVES: This cross-sectional study aimed to estimate total
      antioxidant capacity (TAC) intake from food and beverages in a Japanese
      population from 7-day seasonal dietary records. SUBJECTS/METHODS: The 7-day
      weighed dietary records of 390 subjects over four seasons between 1996 and 1998
      were used. The TAC values (MUmol trolox equivalents (MUmol TE)/g) of various
      foods and beverages were defined, as reported in previous studies for weighed
      dietary records, using several different methods. TAC values of foods were
      estimated in 242 food and beverage items: 86.5% of vegetables, 99.1% of fruits,
      71.5% of potatoes, 96.7% of beans, and 100% of chocolates. Differences in TAC
      intake per day and intake (g) per day among seasons in each of the food and
      beverage group were compared using a general linear model for repeated measures.
      The TAC intake/day were calculated for each food and beverage item in the four
      seasons. RESULTS: TAC intake/day (MUmol TE/day) varied from 10 189 (summer) to 12
      292 (winter). TAC intake/day from fruits (2696) and potatoes (395) was highest in
      autumn, from vegetables (2827) it was highest in summer and from beans (4151) and
      tea (2331) it was highest in winter. CONCLUSIONS: The dietary habits of the
      studied Japanese population showed the highest antioxidant capacity in winter and
      the lowest in summer.

PMID- 24736681
TI  - Bioimpedance phase angle predicts muscle function, quality of life and clinical
      outcome in maintenance hemodialysis patients.
AB  - BACKGROUND/OBJECTIVES: The association of bioimpedance phase angle (PA), as a
      measure of nutritional status, with muscle function, health-related quality of
      life (QoL) and subsequent clinical outcomes in maintenance hemodialysis (MHD)
      patients. SUBJECTS/METHODS: A 2-year prospective observational study on 250 MHD
      outpatients (36.8% women) with a mean age of 68.7+/-13.6 years. Prospective all
      cause and cardiovascular (CV) hospitalization and mortality, malnutrition
      inflammation score (MIS), handgrip strength (HGS), bioimpedance and short form 36
      (SF-36) QoL scores were the study's measurements. RESULTS: Across the three PA
      tertile groups, HGS was incrementally higher in the higher PA tertiles (P<0.001),
      maintaining this order in both male (r=0.38, P<0.001) and female patients
      (r=0.36, P<0.001). Better self-reported QoL was noted with higher PA values. This
      trend was prominent in total score (P<0.001), mental health (P=0.005) and
      physical health (P<0.001) dimensions, and in most of the SF-36 scales. For each 1
      degrees  increase in baseline PA, the first hospitalization hazard ratio (HR) was
      0.79 (95% confidence interval (CI), 0.68-0.91) and first CV event HR was 0.70
      (95% CI, 0.52-0.95); all-cause death HR was 0.63 (95% CI, 0.48-0.81) and CV death
      HR was 0.64 (95% CI, 0.44-0.91). Associations between PA and morbidity risk
      continued to be significant after adjustments for various confounders, but the
      association between PA and mortality risk was abolished after adding MIS to the
      multivariable model. CONCLUSIONS: For the MHD population, PA emerged as a useful
      predictor for impaired muscle function, health-related Qol, upcoming
      hospitalizations and mortality.

PMID- 24736682
TI  - Peterborough trust seeks partner to take it into the black.

PMID- 24736683
TI  - Comparison of DNA-hydrolyzing antibodies from the cerebrospinal fluid and serum
      of patients with multiple sclerosis.
AB  - It was found that high-affinity anti-DNA antibodies were one of the major
      components of the intrathecal IgG response in multiple sclerosis (MS) patients
      [Williamson et al., PNAS, 2001]. Recently we have shown that IgGs from the sera
      of MS patients are active in the hydrolysis of DNA. Here we have shown, for the
      first time, that average concentration of total proteins (132-fold), total IgGs
      (194-fold) and anti-DNA antibodies (200-fold) in the sera is significantly higher
      than that in the cerebrospinal fluid (CSF) of fifteen MS patients. The relative
      activities of total protein from sera and CSFs varied remarkably from patient to
      patient. It was surprising that the specific DNase activity of the total protein
      of CSF reparations were 198-fold higher than the serum ones. Electrophoretically
      and immunologically homogeneous IgGs were obtained by sequential affinity
      chromatography of the CSF proteins on protein G-Sepharose and FPLC gel
      filtration. We present first evidence showing that IgGs from CSF not only bind
      but efficiently hydrolyze DNA and that average specific DNase activity of
      homogeneous antibodies from CSF is unpredictably ~49-fold higher than that from
      the sera of the same MS patients. Some possible reasons of these findings are
      discussed. We suggest that DNase IgGs of CSF may promote important
      neuropathologic mechanisms in this chronic inflammatory disorder and MS
      pathogenesis development. 

PMID- 24736684
TI  - Neurological effects of pesticide use among farmers in China.
AB  - The intensive use of pesticides has attracted great attention from the Chinese
      government. However, current regulations have had limited influence on their safe
      use. Although the acute neurologic effects of pesticides have been well
      documented, little is known about their cumulative effects. Knowledge of the
      impact of pesticides on health may convince farmers to minimize their use. We
      conducted a cross-sectional study in three provinces of China to evaluate the
      relationship between pesticide exposure and neurological dysfunction. Crop
      farmers were divided into two groups depending on their level of pesticide
      exposure. A total of 236 participants were assessed by questionnaire and
      neurological examination for symptoms and signs of neuropathy. Characteristics of
      neurologic dysfunction following cumulative low-level exposure were assessed with
      logistic regression analysis. Farmers exposed to high-level pesticide use had
      greater risk of developing sensations of numbness or prickling (odds ratio (OR)
      2.62, 95% confidence interval (CI): 1.08-6.36). After adjusting for recent
      exposure, the risk of numbness or prickling symptoms (OR 2.55, 95% CI: 1.04-6.25)
      remained statistically significant. Loss of muscle strength and decreased deep
      tendon reflexes had OR > 2, however, this did not reach statistical significance.
      These findings suggest that overuse of pesticides increased risk of neurologic
      dysfunction among farmers, with somatosensory small fibers most likely affected.
      Measures that are more efficient should be taken to curb excessive use of
      pesticides. 

PMID- 24736685
TI  - Economics of obesity--learning from the past to contribute to a better future.
AB  - The discipline of economics plays a varied role in informing the understanding of
      the problem of obesity and the impact of different interventions aimed at
      addressing it. This paper discusses the causes of the obesity epidemic from an
      economics perspective, and outlines various justifications for government
      intervention in this area. The paper then focuses on the potential contribution
      of health economics in supporting resource allocation decision making for obesity
      prevention/treatment. Although economic evaluations of single interventions
      provide useful information, evaluations undertaken as part of a priority setting
      exercise provide the greatest scope for influencing decision making. A review of
      several priority setting examples in obesity prevention/treatment indicates that
      policy (as compared with program-based) interventions, targeted at prevention (as
      compared with treatment) and focused "upstream" on the food environment, are
      likely to be the most cost-effective options for change. However, in order to
      further support decision makers, several methodological advances are required.
      These include the incorporation of intervention costs/benefits outside the health
      sector, the addressing of equity impacts, and the increased engagement of
      decision makers in the priority setting process. 

PMID- 24736686
TI  - Metrics, dose, and dose concept: the need for a proper dose concept in the risk
      assessment of nanoparticles.
AB  - In order to calculate the dose for nanoparticles (NP), (i) relevant information
      about the dose metrics and (ii) a proper dose concept are crucial. Since the
      appropriate metrics for NP toxicity are yet to be elaborated, a general dose
      calculation model for nanomaterials is not available. Here we propose how to
      develop a dose assessment model for NP in analogy to the radiation protection
      dose calculation, introducing the so-called "deposited and the equivalent dose".
      As a dose metric we propose the total deposited NP surface area (SA), which has
      been shown frequently to determine toxicological responses e.g. of lung tissue.
      The deposited NP dose is proportional to the total surface area of deposited NP
      per tissue mass, and takes into account primary and agglomerated NP. By using
      several weighting factors the equivalent dose additionally takes into account
      various physico-chemical properties of the NP which are influencing the
      biological responses. These weighting factors consider the specific surface area,
      the surface textures, the zeta-potential as a measure for surface charge, the
      particle morphology such as the shape and the length-to-diameter ratio (aspect
      ratio), the band gap energy levels of metal and metal oxide NP, and the particle
      dissolution rate. Furthermore, we discuss how these weighting factors influence
      the equivalent dose of the deposited NP. 

PMID- 24736688
TI  - High-resolution mapping of anthropogenic heat in China from 1992 to 2010.
AB  - Anthropogenic heat generated by human activity contributes to urban and regional
      climate warming. Due to the resolution and accuracy of existing anthropogenic
      heat data, it is difficult to analyze and simulate the corresponding effects.
      This study exploited a new method to estimate high spatial and temporal
      resolutions of anthropogenic heat based on long-term data of energy consumption
      and the US Air Force Defense Meteorological Satellite Program-Operational
      Linescan System (DMSP-OLS) data from 1992 to 2010 across China. Our results
      showed that, throughout the entire study period, there are apparent increasing
      trends in anthropogenic heat in three major metropoli, i.e., the Beijing-Tianjin
      region, the Yangzi River delta and the Pearl River delta. The annual mean
      anthropogenic heat fluxes for Beijing, Shanghai and Guangzhou in 2010 were 17 Wm
      2, 19 and 7.8 Wm-2, respectively. Comparisons with previous studies indicate that
      DMSP-OLS data could provide a better spatial proxy for estimating anthropogenic
      heat than population density and our analysis shows better performance at large
      scales for estimation of anthropogenic heat.

PMID- 24736687
TI  - Relationship between obesity, adipocytokines and inflammatory markers in type 2
      diabetes: relevance for cardiovascular risk prevention.
AB  - This study aimed to analyse the impact of obesity in type 2 diabetes (T2D) on
      adipocytokines (adiponectin, leptin and resistin) and inflammatory markers (TNF
      alpha, IL-6 and hsCRP) as cardiovascular risk factors. A cross-sectional study
      comparing the basal levels of adipocytokines and inflammatory markers was done in
      18 obese (BMI >= 30 kg/m2) (group A), 21 overweight (25 kg/m2 <= BMI < 30 kg/m2)
      (group B), 25 non-obese T2D patients (group C) and 15 non-obese controls (group
      D). The lowest levels of adiponectin and the highest levels of leptin, resistin,
      TNF-alpha, IL-6 and hsCRP were found in group A. Adiponectin levels were
      significantly lower, and resistin, TNF-alpha, and hsCRP levels were elevated in
      group C vs. D. However, leptin and IL-6 levels differed significantly between
      groups A and B, but not between groups C and D. Moreover, we found a significant
      negative correlation between adiponectin and TNF-alpha, but not with other
      markers, which was independent of the presence of obesity. In contrast, leptin
      and resistin correlated with the inflammatory markers, and this correlation was
      obesity-dependent. Our results suggest that obesity influences cardiovascular
      risk primarily through changes in leptin and resistin and less efficiently at the
      level of adiponectin.

PMID- 24736689
TI  - The fountain of age: a remarkable 3D shape that portrays health and functional
      differences among the European elderly.
AB  - There are very few norms to evaluate and monitor the health and functioning of
      the elderly. This paper proposes a compact spatial representation of 25 health
      measurements of European citizens older than 50 years. Data from 44,285 unique
      individuals were obtained from the EU-wide Survey of Health, Ageing and
      Retirement in Europe(SHARE) data collected in 2004-2007 and were analyzed by
      homogeneity analysis, a form of non-linear principal components analysis. The
      resulting configuration of persons shows a remarkable three-dimensional shape
      that resembles a fountain. The three components explain 13.7, 5.8 and 4.6 percent
      of the total variation, respectively. Component 1 is driven by age and by the
      disabilities that come with old age. Component 2 portrays differences in health
      that are independent of age, with the high scores in relatively good health,
      given age. Component 3 distinguishes specific types of functional decline from
      general complaints that impact on daily life. The shape suggests that the elderly
      keep on maturing as they grow older, actually becoming more diverse as a group.
      We show how the solution may be used to develop and support profiles for the
      elderly. Another potential application is to track the individual development of
      the elderly, thereby objectifying personalized medicine. 

PMID- 24736690
TI  - Food safety and bioavailability evaluations of four vegetables grown in the
      highly arsenic-contaminated soils on the Guandu Plain of northern Taiwan.
AB  - Arsenic contamination in a large area of agricultural fields on the Guandu Plain
      of northern Taiwan was confirmed in a survey conducted in 2006, but research
      concerning the relationship between bioavailable As concentrations in
      contaminated soils and crop production in Taiwan is not available. Pot
      experiments were conducted to examine the growth and accumulation of As in four
      vegetable crops grown in As-contaminated soils and to assess As intake through
      consumption. The phytotoxic effects of As in soils were not shown in the pot
      experiments in which vegetable crops were grown in soils contaminated with
      different As levels in situ collected from Guandu Plain (120-460 mg/kg) or
      artificially spiked As-contaminated soils (50-170 mg/kg). Experimental results
      showed that the bioavailable As extracted with 0.5M NaHCO3 from soils can be used
      to estimate As concentrations in vegetables. The As concentrations in the
      vegetables were compared with data shown in the literature and As limits
      calculated from drinking water standards and the provisional tolerance weekly
      intake (PTWI) of inorganic As established by the Food and Agriculture
      Organization of the United Nations/World Health Organization (FAO/WHO). Although
      the As levels in the vegetables were not high and the bioavailability of As in
      the soils was quite low, long-term consumption may result in higher As intake in
      the human body. 

PMID- 24736691
TI  - An open source 3-d printed modular micro-drive system for acute neurophysiology.
AB  - Current, commercial, electrode micro-drives that allow independent positioning of
      multiple electrodes are expensive. Custom designed solutions developed by
      individual laboratories require fabrication by experienced machinists working in
      well equipped machine shops and are therefore difficult to disseminate into
      widespread use. Here, we present an easy to assemble modular micro-drive system
      for acute primate neurophysiology (PriED) that utilizes rapid prototyping (3-d
      printing) and readily available off the shelf-parts. The use of 3-d printed parts
      drastically reduces the cost of the device, making it available to labs without
      the resources of sophisticated machine shops. The direct transfer of designs from
      electronic files to physical parts also gives researchers opportunities to easily
      modify and implement custom solutions to specific recording needs. We also
      demonstrate a novel model of data sharing for the scientific community: a
      publicly available repository of drive designs. Researchers can download the
      drive part designs from the repository, print, assemble and then use the drives.
      Importantly, users can upload their modified designs with annotations making them
      easily available for others to use. 

PMID- 24736692
TI  - A visible metamaterial fabricated by self-assembly method.
AB  - A visible negative-index metamaterial was fabricated by adopting a template
      assisted and self-assembled electrochemical deposition method. Originating from
      the inherent characteristic of bottom-up fabrication, it has been demonstrated by
      the effective medium theory that the metamaterial resonance could realize a
      negative index at visible wavelengths if the degree of asymmetry is kept in a
      moderate range. This was experimentally substantiated by fabricating an
      asymmetric Ag-polyvinyl alcohol (PVA)-Ag multilayer nanostructure with two
      apertured silver films on the opposite sides of PVA film. The extraction of
      constitutive parameters shows negative index in the wavelength range from 535 to
      565 nm, with a minimum value close to -0.5. Simultaneously, an optically active
      medium Rhodamine B was incorporated into the PVA layer, which readily changed the
      transmission peak through control experiments. Finally, the enhanced transmission
      was realized through a flat sample.

PMID- 24736693
TI  - Predictive value of ionized calcium in critically ill patients: an analysis of a
      large clinical database MIMIC II.
AB  - BACKGROUND AND OBJECTIVE: Ionized calcium (iCa) has been investigated for its
      association with mortality in intensive care unit (ICU) patients in many studies.
      However, these studies are small in sample size and the results are conflicting.
      The present study aimed to establish the association of iCa with mortality by
      using a large clinical database. METHODS: Multiparameter Intelligent Monitoring
      in Intensive Care II (MIMIC II) database was used for analysis. Patients older
      than 15 years were eligible, and patients without iCa measured during their ICU
      stay were excluded. Demographic data and clinical characteristics were extracted
      and compared between survivors and non-survivors. iCa measure on ICU admission
      was defined as Ca0; Camax was the maximum iCa during ICU stay; Camin was the
      minimum value of iCa during the ICU stay; Camean was the arithmetic mean iCa
      during ICU stay. MAIN RESULTS: A total of 15409 ICU admissions satisfied our
      inclusion criteria and were included in our analysis. The prevalence of
      hypocalcemia on ICU entry was 62.06%. Ca0 was significantly lower in non
      survivors than in survivors (1.11 +/- 0.14 vs 1.13 +/- 0.10 mmol/l, p<0.001). In
      multivariate analysis, moderate hypocalcemia in Ca0 was significantly associated
      with increased risk of death (OR: 1.943; 95% CI: 1.340-2.817), and mild
      hypercalcemia was associated with lower mortality (OR: 0.553, 95% CI: 0.400
      0.767). While moderate and mild hypocalcemia in Camean is associated with
      increased risk of death (OR: 1.153, 95% CI: 1.006-1.322 and OR: 2.520, 95% CI:
      1.485-4.278), hypercalcemia in Camean is not significantly associated with ICU
      mortality. CONCLUSION: The relationship between Ca0 and clinical outcome follows
      an "U" shaped curve with the nadir at the normal range, extending slightly to
      hypercalcemia. Mild hypercalcemia in Ca0 is protective, whereas moderate and mild
      hypocalcemia in Camean is associated with increased risk of death.

PMID- 24736694
TI  - Bleeding risk and mortality of edoxaban: a pooled meta-analysis of randomized
      controlled trials.
AB  - OBJECTIVE(S): Edoxaban, a factor Xa inhibitor, is a new oral anticoagulant that
      has been developed as an alternative to vitamin K antagonists. However, its
      safety remains unexplored. METHODS: Medline, Embase and Web of Science were
      searched to March 8, 2014 for prospective, randomized controlled trials (RCTs)
      that assessed the safety profile of edoxaban with warfarin. Safety outcomes
      examined included bleeding risk and mortality. RESULTS: Five trials including
      31,262 patients that met the inclusion criteria were pooled. Overall, edoxaban
      was associated with a significant decrease in major or clinically relevant
      nonmajor bleeding events [risk ratio (RR) 0.78, 95% confidence interval (CI) 0.74
      to 0.82, p<0.001] and any bleeding events [RR 0.82, 95% CI 0.79 to 0.85,
      p<0.001]. Edoxaban also showed superiority to warfarin both in all-cause
      mortality [RR 0.92, 95% CI 0.85 to 0.99, p = 0.02] and cardiovascular mortality
      [RR 0.87, 95% CI 0.79 to 0.96, p = 0.004]. Subgroup analyses indicated that RRs
      of edoxaban 30, 60 or 120 mg/d were 0.67 (p<0.001), 0.87 (p<0.001) and 3.3 (p =
      0.004) respectively in major or clinically relevant nonmajor bleeding; 0.71
      (p<0.001), 0.89 (p<0.001) and 2.29 (p = 0.002) respectively in any bleeding; as
      well as 0.86 (p = 0.01), 0.87 (p = 0.01) and 0.28 (p = 0.41) respectively in
      cardiovascular death... Meanwhile, paramount to note that pooled results other
      than the largest trial showed edoxaban was still associated with a decrease in
      the rate of major or clinically relevant nonmajor bleeding event (p = 0.02) and
      any bleeding (p = 0.002), but neither in all-cause death (p = 0.66) nor
      cardiovascular death (p = 0.70). CONCLUSIONS: Edoxaban, a novel orally available
      direct factor Xa inhibitor, seems to have a favorable safety profiles with
      respect to bleeding risk and non-inferior in mortality when compared to warfarin.
      Further prospective RCTs are urgently needed to confirm the results of this meta
      analysis.

PMID- 24736695
TI  - Orthopaedic trauma patients and depression: a prospective cohort.
AB  - OBJECTIVES: This study prospectively followed a cohort of orthopaedic trauma
      patients to identify risk factors that contribute to depression in patients with
      skeletal injuries. DESIGN: Prospective cohort study. SETTING: Level I trauma
      center. PATIENTS: One hundred ten orthopaedic trauma patients admitted as
      inpatients. INTERVENTION: None. MAIN OUTCOME MEASUREMENTS: Patient Health
      Questionnaire (PHQ-9) scores. RESULTS: One hundred ten patients were enrolled at
      the time of injury in which 22 patients had moderate-to-major depression and 36
      patients had mild depression. Forty-eight patients completed the follow-up
      surveys that were taken, on average, 9 months after the date of injury. Factors
      that were significant for mild depression (PHQ-9 >4) at the time of injury
      included a history of illegal drug use (P = 0.037) and a lower Duke Social
      Support and Stress Scale (DUSOCS) support score (P = 0.002). The duke social
      support and stress scale score had a negative Pearson correlation coefficient
      with PHQ-9 (n = -0.18, P = 0.03). Factors that were significant for moderate-to
      major depression (PHQ-9 >9) at the time of injury were a history of a psychiatric
      diagnosis (P = 0.0009) and unemployment at injury (P = 0.039). Both a history of
      psychiatric diagnosis and an elevated PHQ-9 score at the time of injury were
      predictors of having depression at 9 months (P = 0.02 and P = 0.001,
      respectively). Also, patients with Medicaid insurance had a significant increase
      in their depression scores at 9 months (P = 0.02). CONCLUSION: Depression was
      quite prevalent in our patient sample. A previous psychiatric diagnosis
      predisposed patients to depression. The socioeconomic status was also a
      predictive factor for increased depression scores at 9 months. Patients with a
      higher feeling of support from friends and family had an inverse correlation for
      depression. Employment also seems to have a protective effect against depression.
      Surprisingly, the severity of injury did not affect the depression score.
      Targeted consultation with a mental health care provider may obviate any
      morbidity that is associated with depression in an injured patient. LEVEL OF
      EVIDENCE: Prognostic Level II. See Instructions for Authors for a complete
      description of levels of evidence.

PMID- 24736696
TI  - Surgical fixation of Vancouver type B1 periprosthetic femur fractures: a
      systematic review.
AB  - OBJECTIVES: Vancouver type B1 periprosthetic femur fractures occur around a
      stable implant and are typically treated with open reduction and internal
      fixation (ORIF). Different fixation techniques are described in the literature,
      and there is a lack of consensus regarding the best operative fixation strategy.
      The purpose of this investigation was to systematically review and compare the
      most commonly used fixation strategies for these fractures. DATA SOURCES: A
      database search was performed using PubMed, MEDLINE, and Cochrane databases to
      identify studies published in English language from 1985 to 2013. STUDY
      SELECTION: Articles with a minimum of 5 patients with type B1 periprosthetic
      femur fractures and containing outcome data regarding nonunion, malunion,
      infection, and reoperation rate were included. DATA EXTRACTION: Studies were
      analyzed and categorized into 4 groups: group 1: ORIF with cortical strut
      allografts alone, group 2: ORIF with cable plate/compression plates alone, group
      3: ORIF with cable plate/compression plates and cortical strut allograft, group
      4: ORIF with locking plates alone. Individual patient outcomes were extracted for
      each study and pooled for each of the 4 groups. Data analysis was performed
      comparing rates of nonunion, malunion, hardware failure, infection, and
      reoperation. DATA SYNTHESIS: Data were analyzed using Review Manager and SAS 9.3.
      CONCLUSIONS: In total, 333 patients identified with an overall rate of 5%
      nonunion, 6% malunion, 5% infection, 4% hardware failure, 9% reoperation, and 15%
      total complications. When comparing outcomes for different modes of fixation,
      compared with cable plate/compression plate systems, locking plates had a
      significantly higher rate of nonunion (3% vs. 9% P = 0.02) and a trend toward a
      higher rate of hardware failure (2% vs. 7%, P = 0.07). There are limitations to
      this study, and further investigation with high-quality randomized controlled
      trials is needed to effectively compare treatment strategies.

PMID- 24736697
TI  - Introduction to the symposium proceedings.

PMID- 24736698
TI  - "Reflections".

PMID- 24736699
TI  - Saliva-microbe interactions and salivary gland dysfunction.
AB  - Adequate salivary secretion is crucial to both oral and general health, since it
      provides a complex milieu for support of the microbial populations of the mouth,
      while at the same time containing antimicrobial products that help control these
      microbial populations. This paper summarizes several aspects of salivary
      component function, gland secretion mechanisms, and immunopathogenesis as related
      to oral health and disease. Salivary components mediate microbial attachment to
      oral surfaces, and also interact with planktonic microbial surfaces to facilitate
      agglutination and elimination of pathogens from the oral cavity. Adhesive
      interactions are often mediated by lectin-like bacterial proteins that bind to
      glycan motifs on salivary glycoproteins. An important salivary antimicrobial
      protein is histatin 5 (Hst 5), which shows potent and selective antifungal
      activity and also susceptibility to proteolytic degradation. Coupling of Hst 5
      with the carrier molecule spermidine significantly enhanced killing of C.
      albicans and resistance to proteolytic degradation, compared with the parent
      peptide. Loss of salivary secretion may be caused by disorders such as Sjogren's
      syndrome (SS) or ectodermal dysplasia, or may be a side-effect of radiation
      therapy. Two new approaches to the treatment of salivary gland dysfunction
      include the use of resolvins and the creation of differentiated acinar structures
      to construct an artificial salivary gland. B-cells contribute to the pathogenesis
      of SS by releasing cytokines and autoantibodies and by influencing T-cell
      differentiation. CXCL13, a potent B-cell chemokine associated with autoimmune
      diseases, is elevated locally and systemically in SS and may represent a novel
      biomarker or therapeutic target in the management and treatment of SS. 

PMID- 24736700
TI  - Genetic characteristics and pathogenic mechanisms of periodontal pathogens.
AB  - Periodontal disease is caused by a group of bacteria that utilize a variety of
      strategies and molecular mechanisms to evade or overcome host defenses. Recent
      research has uncovered new evidence illuminating interesting aspects of the
      virulence of these bacteria and their genomic variability. This paper summarizes
      some of the strategies utilized by the major species - Aggregatibacter
      actinomycetemcomitans, Tannerella forsythia, Treponema denticola, and
      Porphyromonas gingivalis - implicated in the pathogenesis of periodontal disease.
      Whole-genome sequencing of 14 diverse A. actinomycetemcomitans strains has
      revealed variations in their genetic content (ranging between 0.4% and 19.5%) and
      organization. Strikingly, isolates from human periodontal sites showed no genomic
      changes during persistent colonization. T. forsythia manipulates the cytokine
      responses of macrophages and monocytes through its surface glycosylation. Studies
      have revealed that bacterial surface-expressed O-linked glycans modulate T-cell
      responses during periodontal inflammation. Periodontal pathogens belonging to the
      "red complex" consortium express neuraminidases, which enables them to scavenge
      sialic acid from host glycoconjugates. Analysis of recent data has demonstrated
      that the cleaved sialic acid acts as an important nutrient for bacterial growth
      and a molecule for the decoration of bacteria surfaces to help evade the host
      immune attack. In addition, bacterial entry into host cells is also an important
      prerequisite for the lifestyle of periodontal pathogens such as P. gingivalis.
      Studies have shown that, after its entry into the cell, this bacterium uses
      multiple sorting pathways destined for autophagy, lysosomes, or recycling
      pathways. In addition, P. gingivalis releases outer membrane vesicles which enter
      cells via endocytosis and cause cellular functional impairment. 

PMID- 24736701
TI  - Novel inflammatory pathways in periodontitis.
AB  - New insights into the biological mechanisms involved in modulating periodontal
      inflammation and alveolar bone loss are paving the way for novel therapeutic
      strategies for periodontitis. The neutrophil adhesion cascade for transmigration
      in response to infection or inflammation is a key paradigm in immunity.
      Developmental endothelial locus-1 (Del-1) is one of several newly identified
      endogenous inhibitors of the leukocyte adhesion cascade. Del-1 competes with
      intercellular adhesion molecule-1 (ICAM-1) on endothelial cells for binding to
      the LFA-1 integrin on neutrophils, thereby regulating neutrophil recruitment and
      local inflammation. In animal periodontitis models, Del-1 deficiency resulted in
      severe inflammation and alveolar bone loss, but local treatment with recombinant
      Del-1 prevented neutrophil infiltration and bone loss. The expression of Del-1 is
      inhibited by the pro-inflammatory cytokine IL-17. Nucleic-acid-receptor-mediated
      inflammatory responses may be important in periodontal disease pathogenesis.
      Bacterial nucleic acids released during inflammation are detected by host
      microbial DNA sensors, e.g., Toll-like receptor-9 (TLR-9), leading to the
      activation of pro- and/or anti-inflammatory signaling pathways. DNA from
      periodontitis-associated bacteria induced pro-inflammatory cytokine production in
      human macrophage-like cells through the TLR-9 and NF-kappaB signaling pathways,
      but had less effect on human osteoblasts. Inhibition of TLR-9 signaling in human
      macrophages reduced cytokine production in response to P. gingivalis DNA.
      Differential expression of a polymorphic site in the TLR-9 gene promoter region
      and increased TLR-9 gene and protein expression were reported in chronic
      periodontitis. Further research to confirm that periodontal bacterial DNA
      contributes to destructive inflammation in vivo could provide alternative
      therapeutic targets to control periodontitis. 

PMID- 24736702
TI  - Recent advances in host defense mechanisms/therapies against oral infectious
      diseases and consequences for systemic disease.
AB  - The innate and adaptive immune systems are both crucial to oral disease
      mechanisms and their impact on systemic health status. Greater understanding of
      these interrelationships will yield opportunities to identify new therapeutic
      targets to modulate disease processes and/or increase host resistance to
      infectious or inflammatory insult. The topics addressed reflect the latest
      advances in our knowledge of the role of innate and adaptive immune systems and
      inflammatory mechanisms in infectious diseases affecting the oral cavity,
      including periodontitis and candidiasis. In addition, several potential links
      with systemic inflammatory conditions, such as cardiovascular disease, are
      explored. The findings elucidate some of the defense mechanisms utilized by host
      tissues, including the role of IL-17 in providing immunity to oral candidiasis,
      the antimicrobial defense of mucosal epithelial cells, and the pro-resolution
      effects of the natural inflammatory regulators, proresolvins and lipoxins. They
      also describe the role of immune cells in mediating pathologic bone resorption in
      periodontal disease. These insights highlight the potential for therapeutic
      benefit of immunomodulatory interventions that bolster or modulate host defense
      mechanisms in both oral and systemic disease. Among the promising new therapeutic
      approaches discussed here are epithelial cell gene therapy, passive immunization
      against immune cell targets, and the use of proresolvin agents. 

PMID- 24736703
TI  - Alveolar bone loss: mechanisms, potential therapeutic targets, and interventions.
AB  - This article reviews recent research into mechanisms underlying bone resorption
      and highlights avenues of investigation that may generate new therapies to combat
      alveolar bone loss in periodontitis. Several proteins, signaling pathways, stem
      cells, and dietary supplements are discussed as they relate to periodontal bone
      loss and regeneration. RGS12 is a crucial protein that mediates
      osteoclastogenesis and bone destruction, and a potential therapeutic target.
      RGS12 likely regulates osteoclast differentiation through regulating calcium
      influx to control the calcium oscillation-NFATc1 pathway. A working model for
      RGS10 and RGS12 in the regulation of Ca(2+) oscillations during osteoclast
      differentiation is proposed. Initiation of inflammation depends on host cell
      microbe interactions, including the p38 mitogen-activated protein kinase (MAPK)
      signaling pathway. Oral p38 inhibitors reduced lipopolysaccharide (LPS)-induced
      bone destruction in a rat periodontitis model but showed unsatisfactory safety
      profiles. The p38 substrate MK2 is a more specific therapeutic target with
      potentially superior tolerability. Furthermore, MKP-1 shows anti-inflammatory
      activity, reducing inflammatory cytokine biosynthesis and bone resorption.
      Multipotent skeletal stem cell (SSC) populations exist within the bone marrow and
      periosteum of long bones. These bone-marrow-derived SSCs and periosteum-derived
      SSCs have shown therapeutic potential in several applications, including bone and
      periodontal regeneration. The existence of craniofacial bone-specific SSCs is
      suggested based on existing studies. The effects of calcium, vitamin D, and soy
      isoflavone supplementation on alveolar and skeletal bone loss in post-menopausal
      women were investigated. Supplementation resulted in stabilization of forearm
      bone mass density and a reduced rate of alveolar bone loss over 1 yr, compared
      with placebo. Periodontal attachment levels were also well-maintained and
      alveolar bone loss suppressed during 24 wk of supplementation. 

PMID- 24736704
TI  - Periodontal disease, atherosclerosis, adverse pregnancy outcomes, and head-and
      neck cancer.
AB  - Interrelationships between periodontal infection and systemic conditions such as
      cardiovascular disease, adverse pregnancy outcomes, and head-and-neck cancer have
      become increasingly appreciated in recent years. Periodontitis is associated with
      cardiovascular disease (CVD) and, experimentally, with measures of
      atherosclerosis and endothelial dysfunction. Periodontal therapy may reduce
      atherosclerotic changes and improve endothelial function. Preliminary findings
      suggest a role for the genetic locus ANRIL in the pathobiology of both CVD and
      periodontitis. Periodontal pathogens induce anticardiolipin in periodontitis
      patients by molecular mimicry of the serum protein beta-2 glycoprotein I. These
      antibodies have biological and pathological activities consistent with those
      reported for other infection-induced antiphospholipid antibodies. Anticardiolipin
      may explain some of the observed associations between periodontitis and systemic
      conditions such as CVD and adverse pregnancy outcomes. The oral commensal
      Fusobacterium nucleatum (Fn) becomes pathogenic on migration to extra-oral sites.
      Fn infection of the fetal-placental unit has been linked to pregnancy
      complications, including preterm birth, stillbirth, and early-onset neonatal
      sepsis. Reagents aimed at inhibiting or resolving inflammatory responses may be
      used to treat or prevent pregnancy complications due to bacterial infection.
      Chronic periodontitis may be independently associated with head-and-neck squamous
      cell carcinoma (HNSCC) through direct toxic effects of bacteria and their
      products, and/or through indirect effects of inflammation. Additionally, chronic
      periodontitis may facilitate the acquisition and persistence of oral HPV
      infection, a recently emerged risk factor for HNSCC. 

PMID- 24736706
TI  - Meat consumption and risk of oral cavity and oropharynx cancer: a meta-analysis
      of observational studies.
AB  - PURPOSE: High meat consumption, especially red and processed meat consumption is
      associated with an increased risk of several cancers, however, evidence for oral
      cavity and oropharynx cancer is limited. Thus, we performed this meta-analysis to
      determine the association between intakes of total meat, processed meat, red
      meat, and white meat, and the risk of oral cavity and oropharynx cancer. METHODS:
      Electronic search of Pubmed, Embase, and Cochrane Library Central database was
      conducted to select relevant studies. Fixed-effect and random-effect models were
      used to estimate summary relative risks (RR) and the corresponding 95% confidence
      intervals (CIs). Potential sources of heterogeneity were detected by meta
      regression. Subgroup analyses and sensitivity analysis were also performed.
      RESULTS: 12 case-control studies and one cohort study were included in the
      analyses, including 501,730 subjects and 4,104 oral cavity and oropharynx cancer
      cases. Pooled results indicated that high consumption of total meat, red meat,
      and white meat were not significantly associated with increased risk of oral
      cavity and oropharynx cancer (RR = 1.14, 95% CI[0.78-1.68]; RR = 1.05, 95%
      CI[0.66, 1.66] and RR = 0.81, 95% CI[0.54, 1.22], respectively), while the high
      consumption of processed meat was significantly associated with a 91% increased
      risk of oral cavity and oropharynx cancer (RR = 1.91, 95% CI [1.19-3.06]).
      Sensitivity analysis indicated that no significant variation in combined RR by
      excluding any of the study, confirming the stability of present results.
      CONCLUSIONS: The present meta-analysis suggested that high consumption of
      processed meat was significantly associated with an increased risk of oral cavity
      and oropharynx cancer, while there was no significantly association between total
      meat, red meat or white meat and the risk of oral cavity and oropharynx cancer.
      More prospective cohort studies are warranted to confirm these associations.

PMID- 24736707
TI  - Effects of juvenile host density and food availability on adult immune response,
      parasite resistance and virulence in a Daphnia-parasite system.
AB  - Host density can increase infection rates and reduce host fitness as increasing
      population density enhances the risk of becoming infected either through
      increased encounter rate or because host condition may decline. Conceivably,
      potential hosts could take high host density as a cue to up-regulate their
      defence systems. However, as host density usually covaries with food
      availability, it is difficult to examine the importance of host density in
      isolation. Thus, we performed two full-factorial experiments that varied juvenile
      densities of Daphnia magna (a freshwater crustacean) and food availability
      independently. We also included a simulated high-density treatment, where
      juvenile experimental animals were kept in filtered media that previously
      maintained Daphnia at high-density. Upon reaching adulthood, we exposed the
      Daphnia to their sterilizing bacterial parasite, Pasteuria ramosa, and examined
      how the juvenile treatments influenced the likelihood and severity of infection
      (Experiment I) and host immune investment (Experiment II). Neither juvenile
      density nor food treatments affected the likelihood of infection; however, well
      fed hosts that were well-fed as juveniles produced more offspring prior to
      sterilization than their less well-fed counterparts. By contrast, parasite growth
      was independent of host juvenile resources or host density. Parasite-exposed
      hosts had a greater number of circulating haemocytes than controls (i.e., there
      was a cellular immune response), but the magnitude of immune response was not
      mediated by food availability or host density. These results suggest that density
      dependent effects on disease arise primarily through correlated changes in food
      availability: low food could limit parasitism and potentially curtail epidemics
      by reducing both the host's and parasite's reproduction as both depend on the
      same food. 

PMID- 24736708
TI  - Enhancing maternal child nursing practice through ethical insight.

PMID- 24736709
TI  - Should there be a limit of one single embryo implanted during an IVF cycle?

PMID- 24736715
TI  - Medically provided hydration and nutrition in infants: ethical considerations.

PMID- 24736716
TI  - Ethical perspectives of the personal health record.

PMID- 24736717
TI  - A compelling human rights ethical issue: female genital mutilation.

PMID- 24736719
TI  - Informed consent in the perinatal setting.

PMID- 24736720
TI  - Implementation of a national measles elimination program in Iran: Phylogenetic
      analysis of measles virus strains isolated during 2010-2012 outbreaks.
AB  - Measles virus (MV) causes small and large outbreaks in Iran. Molecular assays
      allow identifying and the sources of measles imported from neighboring countries.
      We carried out a phylogenetic analysis of measles virus circulating in Iran over
      the period 2010-2012. Specimens from suspected cases of measles were collected
      from different regions of Iran. Virus isolation was performed on urine and throat
      swabs. Partial nucleoprotein gene segments of MV were amplified by RT-PCR. PCR
      products of 173 samples were sequenced and analyzed. The median age of confirmed
      cases was 2 years. Among all confirmed cases, 32% had unknown vaccination status,
      20% had been vaccinated, and 48% had not been vaccinated. Genotypes B3 and D8
      (for the first time), H1 and D4 were detected mainly in unvaccinated toddlers and
      young children. Genotype B3 became predominant in 2012 and was closely related to
      African strains. H1 strains were also found in small and large outbreaks during
      2012 but were not identical to Iranian H1-2009 strains. A majority of the Iranian
      D4 strains during 2010-2012 outbreaks were linked to the D4 strain identified in
      the Pakistan in 2007. We identified a single case in 2010 belonging to D8
      genotype with 99.7% identity to Indian isolates. Although the vaccination program
      is currently good enough to prevent nationwide epidemics and successfully
      decreased measles incidence in Iran, the fraction of protected individuals in the
      population was not high enough to prevent continuous introduction of cases from
      abroad. Due to increasing number of susceptible individuals in some areas,
      sustained transmission of the newly introduced viral genotype remains possible. 

PMID- 24736722
TI  - Characterization of the role of tumor necrosis factor apoptosis inducing ligand
      (TRAIL) in spermatogenesis through the evaluation of trail gene-deficient mice.
AB  - TRAIL (TNFSF10/Apo2L) is a member of the tumor necrosis factor (TNF) superfamily
      of proteins and is expressed in human and rodent testis. Although the functional
      role of TRAIL in spermatogenesis is not known, TRAIL is recognized to induce
      apoptosis via binding to its cognate receptors; DR4 (TRAIL-R1/TNFRSF10A) and DR5
      (TRAIL-R2/TNFRSF10B). Here, we utilize Trail gene-deficient (Trail-/-) mice to
      evaluate the role of TRAIL in spermatogenesis by measuring testis weight, germ
      cell apoptosis, and spermatid head count at postnatal day (PND) 28 (pubertal) and
      PND 56 (adult). Trail-/- mice have significantly reduced testis to body weight
      ratios as compared to wild-type C57BL/6J at both ages. Also, Trail-/- mice (PND
      28) show a dramatic increase in basal germ cell apoptotic index (AI, 16.77) as
      compared to C57BL/6J (3.5). In the testis of adult C57BL/6J mice, the AI was
      lower than in PND 28 C57BL/6J mice (2.2). However, in adult Trail-/- mice, the AI
      was still higher than that of controls (9.0); indicating a relative high
      incidence of germ cell apoptosis. Expression of cleaved caspase-8 (CC8) and
      cleaved caspase-9 (CC9) (markers of the extrinsic and intrinsic apoptotic
      pathway, respectively) revealed a two-fold increase in the activity of both
      pathways in adult Trail-/- mice compared to C57BL/6J. Spermatid head counts in
      adult Trail-/- mice were dramatically reduced by 54% compared to C57BL/6J,
      indicating these animals suffer a marked decline in the production of mature
      spermatozoa. Taken together, these findings indicate that TRAIL is an important
      signaling molecule for maintaining germ cell homeostasis and functional
      spermatogenesis in the testis. 

PMID- 24736721
TI  - Heat shock alters the expression of schizophrenia and autism candidate genes in
      an induced pluripotent stem cell model of the human telencephalon.
AB  - Schizophrenia (SZ) and autism spectrum disorders (ASD) are highly heritable
      neuropsychiatric disorders, although environmental factors, such as maternal
      immune activation (MIA), play a role as well. Cytokines mediate the effects of
      MIA on neurogenesis and behavior in animal models. However, MIA stimulators can
      also induce a febrile reaction, which could have independent effects on
      neurogenesis through heat shock (HS)-regulated cellular stress pathways. However,
      this has not been well-studied. To help understand the role of fever in MIA, we
      used a recently described model of human brain development in which induced
      pluripotent stem cells (iPSCs) differentiate into 3-dimensional neuronal
      aggregates that resemble a first trimester telencephalon. RNA-seq was carried out
      on aggregates that were heat shocked at 39 degrees C for 24 hours, along with
      their control partners maintained at 37 degrees C. 186 genes showed significant
      differences in expression following HS (p<0.05), including known HS-inducible
      genes, as expected, as well as those coding for NGFR and a number of SZ and ASD
      candidates, including SMARCA2, DPP10, ARNT2, AHI1 and ZNF804A. The degree to
      which the expression of these genes decrease or increase during HS is similar to
      that found in copy loss and copy gain copy number variants (CNVs), although the
      effects of HS are likely to be transient. The dramatic effect on the expression
      of some SZ and ASD genes places HS, and perhaps other cellular stressors, into a
      common conceptual framework with disease-causing genetic variants. The findings
      also suggest that some candidate genes that are assumed to have a relatively
      limited impact on SZ and ASD pathogenesis based on a small number of positive
      genetic findings, such as SMARCA2 and ARNT2, may in fact have a much more
      substantial role in these disorders - as targets of common environmental
      stressors. 

PMID- 24736724
TI  - Constitutive model of single root system's resistance to tensile stress - taking
      Pinus tabulaeformis, Betula platyphylla, Quercus mongolica and Larix gmelinii as
      experimental objects.
AB  - A constitutive model for the stress-strain relationship of single forest root
      system was developed in order to provide theoretical foundations for the
      mechanisms of soil-reinforcement by root system and offer a reliable basis for
      the analysis of root tensile strength character. This study started a general
      form of linear and non-linear stress-strain relation that was mathematically
      defined by four boundary conditions observed in typical tensile tests of single
      roots. The parameters of the model were determined by experiment data and had
      definite physical meaning. The model was verified by experiment data, which
      showed that the calculated values were in good agreement with the experimental
      single root tensile test results. The constitutive model was validated and found
      to be feasible for modeling single root tensile stress. 

PMID- 24736723
TI  - Acute coronary syndrome remodels the protein cargo and functions of high-density
      lipoprotein subfractions.
AB  - OBJECTIVES: This study examined alterations in the functions and proteome of high
      density lipoprotein (HDL) subfractions (HDL2 and HDL3) isolated from patients
      with acute coronary syndrome (ACS) compared with control subjects. METHODS: We
      measured HDL subfraction cholesterol efflux capacity, inflammatory index (HII),
      paraoxonase-1 (PON1) activity, and lipid hydroperoxide (LOOH) levels in both male
      age-matched controls and the ACS group (n = 40/group). Additionally, proteomic
      analysis was used to monitor changes in the HDL subfraction proteome between
      controls and ACS subjects. RESULTS: Both HDL2 and HDL3 from ACS patients had
      greater HII and LOOH levels compared with controls (P<0.001); PON1 activity and
      cholesterol efflux capacity in both HDL2 and HDL3 from the ACS group were
      significantly less than those of controls (P<0.001). Using proteomic analysis, we
      demonstrated that, compared with the control group, nine proteins were
      selectively enriched in HDL3 from subjects with ACS, and ras-related protein Rab
      7b was decreased in HDL3. Additionally, in the ACS subjects, 12 proteins were
      decreased in HDL2 and 4 proteins were increased in HDL2. CONCLUSIONS: Functional
      HDL subfractions shifted to dysfunctional HDL subfractions during ACS, and the
      functional impairment was linked to remodeled protein cargo in HDL subfractions
      from ACS patients.

PMID- 24736725
TI  - Characterizing the time-perspective of nations with search engine query data.
AB  - Vast quantities of data on human behavior are being created by our everyday
      internet usage. Building upon a recent study by Preis, Moat, Stanley, and Bishop
      (2012), we used search engine query data to construct measures of the time
      perspective of nations, and tested these measures against per-capita gross
      domestic product (GDP). The results indicate that nations with higher per-capita
      GDP are more focused on the future and less on the past, and that when these
      nations do focus on the past, it is more likely to be the distant past. These
      results demonstrate the viability of using nation-level data to build
      psychological constructs.

PMID- 24736726
TI  - ASK1 promotes the contact hypersensitivity response through IL-17 production.
AB  - Contact hypersensitivity (CHS) is a form of delayed-type hypersensitivity
      triggered by the response to reactive haptens (sensitization) and subsequent
      challenge (elicitation). Here, we show that ASK1 promotes CHS and that
      suppression of ASK1 during the elicitation phase is sufficient to attenuate CHS.
      ASK1 knockout (KO) mice exhibited impaired 2,4-dinitrofluorobenzene (DNFB)
      induced CHS. The suppression of ASK1 activity during the elicitation phase
      through a chemical genetic approach or a specific inhibitory compound
      significantly reduced the CHS response to a level similar to that observed in
      ASK1 KO mice. The reduced response was concomitant with the strong inhibition of
      production of IL-17, a cytokine that plays an important role in CHS and other
      inflammatory diseases, from sensitized lymph node cells. These results suggest
      that ASK1 is relevant to the overall CHS response during the elicitation phase
      and that ASK1 may be a promising therapeutic target for allergic contact
      dermatitis and other IL-17-related inflammatory diseases. 

PMID- 24736727
TI  - MiR-330-mediated regulation of SH3GL2 expression enhances malignant behaviors of
      glioblastoma stem cells by activating ERK and PI3K/AKT signaling pathways.
AB  - MicroRNAs are currently considered as an active and rapidly evolving area for the
      treatment of tumors. In this study, we elucidated the biological significance of
      miR-330 in glioblastoma stem cells (GSCs) as well as the possible molecular
      mechanisms. SH3GL2 is mainly distributed in the central nervous system and
      considered to be a tumor suppressor in many tumors. In the present study, we
      identified miR-330 as a potential regulator of SH3GL2 and we found that it was to
      be inversely correlated with SH3GL2 expression in GSCs which were isolated from
      U87 cell lines. The expression of miR-330 enhanced cellular proliferation,
      promoted cell migration and invasion, and dampened cell apoptosis. When the GSCs
      were co-transfected with the plasmid containing short hairpin RNA directed
      against human SH3GL2 gene and miR-330 mimic, we found that miR-330 promoted the
      malignant behavior of GSCs by down-regulating the expression of SH3GL2.
      Meanwhile, the ERK and PI3K/AKT signaling pathways were significantly activated,
      leading to the decreased expression of apoptotic protein and increased expression
      of anti-apoptotic protein. Furthermore, in orthotopic mouse xenografts, the mice
      given stable over-expressed SH3GL2 cells co-transfected with miR-330 knockdown
      plasmid had the smallest tumor sizes and longest survival. In conclusion, these
      results suggested that miR-330 negatively regulated the expression of SH3GL2 in
      GSCs, which promoted the oncogenic progression of GSCs through activating ERK and
      PI3K/AKT signaling pathways. The elucidation of these mechanisms will provide
      potential therapeutic approaches for human glioblastoma. 

PMID- 24736728
TI  - Genetic analysis of high bone mass cases from the BARCOS cohort of Spanish
      postmenopausal women.
AB  - The aims of the study were to establish the prevalence of high bone mass (HBM) in
      a cohort of Spanish postmenopausal women (BARCOS) and to assess the contribution
      of LRP5 and DKK1 mutations and of common bone mineral density (BMD) variants to a
      HBM phenotype. Furthermore, we describe the expression of several osteoblast
      specific and Wnt-pathway genes in primary osteoblasts from two HBM cases. A 0.6%
      of individuals (10/1600) displayed Z-scores in the HBM range (sum Z-score >4).
      While no mutation in the relevant exons of LRP5 was detected, a rare missense
      change in DKK1 was found (p.Y74F), which cosegregated with the phenotype in a
      small pedigree. Fifty-five BMD SNPs from Estrada et al. [NatGenet 44:491
      501,2012] were genotyped in the HBM cases to obtain risk scores for each
      individual. In this small group of samples, Z-scores were found inversely related
      to risk scores, suggestive of a polygenic etiology. There was a single exception,
      which may be explained by a rare penetrant genetic variant, counterbalancing the
      additive effect of the risk alleles. The expression analysis in primary
      osteoblasts from two HBM cases and five controls suggested that IL6R, DLX3,
      TWIST1 and PPARG are negatively related to Z-score. One HBM case presented with
      high levels of RUNX2, while the other displayed very low SOX6. In conclusion, we
      provide evidence of lack of LRP5 mutations and of a putative HBM-causing mutation
      in DKK1. Additionally, we present SNP genotyping and expression results that
      suggest additive effects of several genes for HBM. 

PMID- 24736729
TI  - Perceived social support moderates the link between attachment anxiety and health
      outcomes.
AB  - Two literatures have explored some of the effects intimate relationships can have
      on physical and mental health outcomes. Research investigating health through the
      lens of attachment theory has demonstrated that more anxiously attached
      individuals in particular consistently report poorer health. Separate research on
      perceived social support (e.g., partner or spousal support) suggests that higher
      support has salutary influences on various health outcomes. Little to no
      research, however, has explored the interaction of attachment anxiety and
      perceived social support on health outcomes. The present study examined the
      attachment-health link and the moderating role of perceived social support in a
      community sample of married couples. Results revealed that more anxious persons
      reported poorer overall physical and mental health, more bodily pain, more
      medical symptoms, and impaired daily functioning, even after controlling for age,
      relationship length, neuroticism, and marital quality. Additionally, perceived
      social support interacted with attachment anxiety to influence health; more
      anxious individuals' health was poorer even when perceived social support was
      high, whereas less anxious individuals' health benefited from high support.
      Possible mechanisms underlying these findings and the importance of considering
      attachment anxiety in future studies of poor health in adulthood are discussed. 

PMID- 24736730
TI  - Quantification of encapsulated bioburden in spacecraft polymer materials by
      cultivation-dependent and molecular methods.
AB  - Bioburden encapsulated in spacecraft polymers (such as adhesives and coatings)
      poses a potential risk to jeopardize scientific exploration of other celestial
      bodies. This is particularly critical for spacecraft components intended for hard
      landing. So far, it remained unclear if polymers are indeed a source of microbial
      contamination. In addition, data with respect to survival of microbes during the
      embedding/polymerization process are sparse. In this study we developed testing
      strategies to quantitatively examine encapsulated bioburden in five different
      polymers used frequently and in large quantities on spaceflight hardware. As
      quantitative extraction of the bioburden from polymerized (solid) materials did
      not prove feasible, contaminants were extracted from uncured precursors.
      Cultivation-based analyses revealed <0.1-2.5 colony forming units (cfu) per cm3
      polymer, whereas quantitative PCR-based detection of contaminants indicated
      considerably higher values, despite low DNA extraction efficiency. Results
      obtained from this approach reflect the most conservative proxy for encapsulated
      bioburden, as they give the maximum bioburden of the polymers irrespective of any
      additional physical and chemical stress occurring during polymerization. To
      address the latter issue, we deployed an embedding model to elucidate and monitor
      the physiological status of embedded Bacillus safensis spores in a cured polymer.
      Staining approaches using AlexaFluor succinimidyl ester 488 (AF488), propidium
      monoazide (PMA), CTC (5-cyano-2,3-diotolyl tetrazolium chloride) demonstrated
      that embedded spores retained integrity, germination and cultivation ability even
      after polymerization of the adhesive Scotch-Weld 2216 B/A. Using the methods
      presented here, we were able to estimate the worst case contribution of
      encapsulated bioburden in different polymers to the bioburden of spacecraft. We
      demonstrated that spores were not affected by polymerization processes. Besides
      Planetary Protection considerations, our results could prove useful for the
      manufacturing of food packaging, pharmacy industry and implant technology. 

PMID- 24736731
TI  - Formation of sclerotia and production of indoloterpenes by Aspergillus niger and
      other species in section Nigri.
AB  - Several species in Aspergillus section Nigri have been reported to produce
      sclerotia on well-known growth media, such as Czapek yeast autolysate (CYA) agar,
      with sclerotia considered to be an important prerequisite for sexual development.
      However Aspergillus niger sensu stricto has not been reported to produce
      sclerotia, and is thought to be a purely asexual organism. Here we report, for
      the first time, the production of sclerotia by certain strains of Aspergillus
      niger when grown on CYA agar with raisins, or on other fruits or on rice. Up to
      11 apolar indoloterpenes of the aflavinine type were detected by liquid
      chromatography and diode array and mass spectrometric detection where sclerotia
      were formed, including 10,23-dihydro-24,25-dehydroaflavinine. Sclerotium
      induction can thus be a way of inducing the production of new secondary
      metabolites from previously silent gene clusters. Cultivation of other species of
      the black aspergilli showed that raisins induced sclerotium formation by A.
      brasiliensis, A. floridensis A. ibericus, A. luchuensis, A. neoniger, A.
      trinidadensis and A. saccharolyticus for the first time. 

PMID- 24736732
TI  - Combination of hypomorphic mutations of the Drosophila homologues of aryl
      hydrocarbon receptor and nucleosome assembly protein family genes disrupts
      morphogenesis, memory and detoxification.
AB  - Aryl hydrocarbon receptor is essential for biological responses to endogenous and
      exogenous toxins in mammals. Its Drosophila homolog spineless plays an important
      role in fly morphogenesis. We have previously shown that during morphogenesis
      spineless genetically interacts with CG5017 gene, which encodes a nucleosome
      assembly factor and may affect cognitive function of the fly. We now demonstrate
      synergistic interactions of spineless and CG5017 in pathways controlling
      oxidative stress response and long-term memory formation in Drosophila
      melanogaster. Oxidative stress was induced by low doses of X-ray irradiation of
      flies carrying hypomorphic mutation of spineless, mutation of CG5017, and their
      combination. To determine the sensitivity of these mutants to pharmacological
      modifiers of the irradiation effect, we irradiated flies growing on standard
      medium supplemented by radiosensitizer furazidin and radioprotector serotonin.
      The effects of irradiation were investigated by analyzing leg and antenna
      morphological structures and by using real-time PCR to measure mRNA expression
      levels for spineless, Cyp6g1 and Gst-theta genes. We also examined long-term
      memory in these mutants using conditioned courtship suppression paradigm. Our
      results show that the interaction of spineless and CG5017 is important for
      regulation of morphogenesis, long-term memory formation, and detoxification
      during oxidative stress. Since spineless and CG5017 are evolutionary conserved,
      these results must be considered when evaluating the risk of combining similar
      mutations in other organisms, including humans. 

PMID- 24736734
TI  - Clinical utility gene card for: Prader-Willi Syndrome.

PMID- 24736733
TI  - The SMAD-binding domain of SKI: a hotspot for de novo mutations causing
      Shprintzen-Goldberg syndrome.
AB  - Shprintzen-Goldberg syndrome (SGS) is a rare, systemic connective tissue disorder
      characterized by craniofacial, skeletal, and cardiovascular manifestations that
      show a significant overlap with the features observed in the Marfan (MFS) and
      Loeys-Dietz syndrome (LDS). A distinguishing observation in SGS patients is the
      presence of intellectual disability, although not all patients in this series
      present this finding. Recently, SGS was shown to be due to mutations in the SKI
      gene, encoding the oncoprotein SKI, a repressor of TGFbeta activity. Here, we
      report eight recurrent and three novel SKI mutations in eleven SGS patients. All
      were heterozygous missense mutations located in the R-SMAD binding domain, except
      for one novel in-frame deletion affecting the DHD domain. Adding our new findings
      to the existing data clearly reveals a mutational hotspot, with 73% (24 out of
      33) of the hitherto described unrelated patients having mutations in a stretch of
      five SKI residues (from p.(Ser31) to p.(Pro35)). This implicates that the initial
      molecular testing could be focused on mutation analysis of the first half of exon
      1 of SKI. As the majority of the known mutations are located in the R-SMAD
      binding domain of SKI, our study further emphasizes the importance of TGFbeta
      signaling in the pathogenesis of SGS. 

PMID- 24736735
TI  - New insights into genotype-phenotype correlation for GLI3 mutations.
AB  - The phenotypic spectrum of GLI3 mutations includes autosomal dominant Greig
      cephalopolysyndactyly syndrome (GCPS) and Pallister-Hall syndrome (PHS). PHS was
      first described as a lethal condition associating hypothalamic hamartoma,
      postaxial or central polydactyly, anal atresia and bifid epiglottis. Typical GCPS
      combines polysyndactyly of hands and feet and craniofacial features. Genotype
      phenotype correlations have been found both for the location and the nature of
      GLI3 mutations, highlighting the bifunctional nature of GLI3 during development.
      Here we report on the molecular and clinical study of 76 cases from 55 families
      with either a GLI3 mutation (49 GCPS and 21 PHS), or a large deletion
      encompassing the GLI3 gene (6 GCPS cases). Most of mutations are novel and
      consistent with the previously reported genotype-phenotype correlation. Our
      results also show a correlation between the location of the mutation and abnormal
      corpus callosum observed in some patients with GCPS. Fetal PHS observations
      emphasize on the possible lethality of GLI3 mutations and extend the phenotypic
      spectrum of malformations such as agnathia and reductional limbs defects. GLI3
      expression studied by in situ hybridization during human development confirms its
      early expression in target tissues. 

PMID- 24736737
TI  - Clinical spectrum and outcomes in families with coronal synostosis and TCF12
      mutations.
AB  - TCF12 mutations have been reported very recently in coronal synostosis. We report
      several cases of familial coronal synostosis among four families harbouring novel
      TCF12 mutations. We observed a broad interfamilial phenotypic spectrum with
      features overlapping with the Saethre-Chotzen syndrome. TCF12 molecular testing
      should be considered in patients with unilateral- or bilateral-coronal synostosis
      associated or not with syndactyly, after having excluded mutations in the TWIST1
      gene and the p.Pro250Arg mutation in FGFR3. 

PMID- 24736736
TI  - Delineation of candidate genes responsible for structural brain abnormalities in
      patients with terminal deletions of chromosome 6q27.
AB  - Patients with terminal deletions of chromosome 6q present with structural brain
      abnormalities including agenesis of corpus callosum, hydrocephalus,
      periventricular nodular heterotopia, and cerebellar malformations. The 6q27
      region harbors genes that are important for the normal development of brain and
      delineation of a critical deletion region for structural brain abnormalities may
      lead to a better genotype-phenotype correlation. We conducted a detailed clinical
      and molecular characterization of seven unrelated patients with deletions
      involving chromosome 6q27. All patients had structural brain abnormalities. Using
      array comparative genomic hybridization, we mapped the size, extent, and genomic
      content of these deletions. The smallest region of overlap spans 1.7 Mb and
      contains DLL1, THBS2, PHF10, and C6orf70 (ERMARD) that are plausible candidates
      for the causation of structural brain abnormalities. Our study reiterates the
      importance of 6q27 region in normal development of brain and helps identify
      putative genes in causation of structural brain anomalies. 

PMID- 24736738
TI  - A decade of molecular genetic testing for MODY: a retrospective study of
      utilization in The Netherlands.
AB  - Genetic testing for maturity-onset diabetes of the young (MODY) may be relevant
      for treatment and prognosis in patients with usually early-onset, non-ketotic,
      insulin-sensitive diabetes and for monitoring strategies in non-diabetic mutation
      carriers. This study describes the first 10 years of genetic testing for MODY in
      The Netherlands in terms of volume and test positive rate, medical setting,
      purpose of the test and age of patients tested. Some analyses focus on the most
      prevalent subtype, HNF1A MODY. Data were retrospectively extracted from a
      laboratory database. In total, 502 individuals were identified with a pathogenic
      mutation in HNF4A, GCK or HNF1A between 2001 and 2010. Although mutation scanning
      for MODY was used at an increasing rate, cascade testing was only used for one
      relative, on average, per positive index patient. Testing for HNF1A MODY was
      mostly requested by internists and paediatricians, often from regional hospitals.
      Primary care physicians and clinical geneticists rarely requested genetic testing
      for HNF1A MODY. Clinical geneticists requested cascade testing relatively more
      often than other health professionals. A substantial proportion (currently 29%)
      of HNF1A MODY probands was at least 40 years old at the time of testing. In
      conclusion, the number of individuals genetically tested for MODY so far in The
      Netherlands is low compared with previously predicted numbers of patients.
      Doctors' valuation of the test and patients' and family members' response to (an
      offer of) genetic testing on the other hand need to be investigated. Efforts may
      be needed to develop and implement translational guidelines. 

PMID- 24736739
TI  - Association of XPC polymorphisms and lung cancer risk: a meta-analysis.
AB  - BACKGROUND: Xeroderma pigmentosum complementation group C gene (XPC) is a key
      member of nucleotide excision repair pathway and plays an important role in human
      DNA repair system. It is reported that several common polymorphisms of XPC are
      associated with susceptibility to lung cancer. However, the conclusion is still
      elusive. METHOD: This meta-analysis was performed to determine the relationship
      between XPC polymorphisms (Lys939Gln, Ala499Val, and PAT) and lung cancer risk.
      Published literatures were identified by searching online databases and reference
      lists of relevant studies. Odds ratios (ORs) and 95% confidence intervals (CIs)
      were calculated to estimate the association strength. Publication bias were
      detected by Egger's and Begg's test. RESULT: After strict screening, we
      identified 14 eligible studies in this meta-analysis, including 5647 lung cancer
      cases and 6908 controls. By pooling all eligible studies, we found that the
      homozygote Gln939Gln genotype was associated with a significantly increased risk
      of lung cancer in Asian population (GlnGln vs LysLys, OR=1.229, 95% CI: 1.000
      1.510; GlnGln vs LysLys/LysGln, OR=1.257, 95% CI: 1.038-1.522). As for the PAT
      polymorphism, in Caucasian population, we found carriers of the -/- genotype were
      associated significantly reduced risk of lung cancer in homozygote comparison
      model (-/- vs +/+, OR=0.735, 95% CI: 0.567-0.952). CONCLUSION: In this meta
      analysis we found that Gln939Gln genotype was associated with significantly
      increased risk of lung cancer in Asian population; the PAT -/- genotype
      significantly reduced susceptibility to lung cancer in Caucasian population;
      while the XPC Ala499Val polymorphism was not associated with lung cancer risk.

PMID- 24736740
TI  - Experimentally induced stress validated by EMG activity.
AB  - Experience of stress may lead to increased electromyography (EMG) activity in
      specific muscles compared to a non-stressful situation. The main aim of this
      study was to develop and validate a stress-EMG paradigm in which a single
      uncontrollable and unpredictable nociceptive stimulus was presented. EMG activity
      of the trapezius muscles was the response of interest. In addition to linear time
      effects, non-linear EMG time courses were also examined. Taking into account the
      hierarchical structure of the dataset, a multilevel random regression model was
      applied. The stress paradigm, executed in N = 70 subjects, consisted of a 3
      minute baseline measurement, a 3-minute pre-stimulus stress period and a 2-minute
      post-stimulus phase. Subjects were unaware of the precise moment of stimulus
      delivery and its intensity level. EMG activity during the entire experiment was
      conform a priori expectations: the pre-stimulus phase showed a significantly
      higher mean EMG activity level compared to the other two phases, and an immediate
      EMG response to the stimulus was demonstrated. In addition, the analyses revealed
      significant non-linear EMG time courses in all three phases. Linear and quadratic
      EMG time courses were significantly modified by subjective anticipatory stress
      level, measured just before the start of the stress task. Linking subjective
      anticipatory stress to EMG stress reactivity revealed that subjects with a high
      anticipatory stress level responded with more EMG activity during the pre
      stimulus stress phase, whereas subjects with a low stress level showed an inverse
      effect. Results suggest that the stress paradigm presented here is a valid test
      to quantify individual differences in stress susceptibility. Further studies with
      this paradigm are required to demonstrate its potential use in mechanistic
      clinical studies.

PMID- 24736741
TI  - Insulin-like growth factor 1 predicts post-load hypoglycemia following bariatric
      surgery: a prospective cohort study.
AB  - Postprandial hypoglycemia is a complication following gastric bypass surgery,
      which frequently remains undetected. Severe hypoglycemic episodes, however, put
      patients at risk, e.g., for syncope. A major cause of hypoglycemia following
      gastric bypass is hyperinsulinemic nesidioblastosis. Since pancreatic islets in
      nesidioblastosis overexpress insulin-like growth factor 1 (IGF-1) receptor alpha
      and administration of recombinant IGF-1 provokes hypoglycemia, our main objective
      was to investigate the occurrence of post-load hypoglycemia one year after
      bariatric surgery and its relation to pre- and post-operative IGF-1 serum
      concentrations. We evaluated metabolic parameters including 2 h 75 g oral glucose
      tolerance test (OGTT) and measured IGF-1 serum concentration in thirty-six non
      diabetic patients (29 f/7 m), aged 41.3+/-2.0 y with a median (IQR) BMI of 30.9
      kg/m2 (27.5-34.3 kg/m2), who underwent elective bariatric surgery (predominantly
      gastric bypass, 83%) at our hospital. Post-load hypoglycemia as defined by a 2 h
      glucose concentration <60 mg/dl was detected in 50% of patients. Serum insulin
      and C-peptide concentration during the OGTT and HOMA-IR (homeostatic model
      assessment-insulin resistance) were similar in hypoglycemic and euglycemic
      patients. Strikingly, pre- and post-operative serum IGF-1 concentrations were
      significantly higher in hypoglycemic patients (p = 0.012 and p = 0.007
      respectively). IGF-1 serum concentration before surgery negatively correlated
      with 2 h glucose concentration during the OGTT (rho = -0.58, p = 0.0003).
      Finally, IGF-1 serum concentrations before and after surgery significantly
      predicted post-load hypoglycemia with odds ratios of 1.28 (95%CI:1.03-1.55, p =
      0.029) and 1.18 (95%CI:1.03-1.33, p = 0.015), respectively, for each 10 ng/ml
      increment. IGF-1 serum concentration could be a valuable biomarker to identify
      patients at risk for hypoglycemia following bariatric surgery independently of a
      diagnostic OGTT. Thus, IGF-1 testing could help to prevent a significant
      complication of gastric bypass surgery. 

PMID- 24736742
TI  - Statistical optimization of ultraviolet irradiate conditions for vitamin D2
      synthesis in oyster mushrooms (Pleurotus ostreatus) using response surface
      methodology.
AB  - Response surface methodology (RSM) was used to determine the optimum vitamin D2
      synthesis conditions in oyster mushrooms (Pleurotus ostreatus). Ultraviolet B (UV
      B) was selected as the most efficient irradiation source for the preliminary
      experiment, in addition to the levels of three independent variables, which
      included ambient temperature (25-45 degrees C), exposure time (40-120 min), and
      irradiation intensity (0.6-1.2 W/m2). The statistical analysis indicated that,
      for the range which was studied, irradiation intensity was the most critical
      factor that affected vitamin D2 synthesis in oyster mushrooms. Under optimal
      conditions (ambient temperature of 28.16 degrees C, UV-B intensity of 1.14 W/m2,
      and exposure time of 94.28 min), the experimental vitamin D2 content of 239.67
      ug/g (dry weight) was in very good agreement with the predicted value of 245.49
      ug/g, which verified the practicability of this strategy. Compared to fresh
      mushrooms, the lyophilized mushroom powder can synthesize remarkably higher level
      of vitamin D2 (498.10 ug/g) within much shorter UV-B exposure time (10 min), and
      thus should receive attention from the food processing industry.

PMID- 24736743
TI  - A trisubstituted benzimidazole cell division inhibitor with efficacy against
      Mycobacterium tuberculosis.
AB  - Trisubstituted benzimidazoles have demonstrated potency against Gram-positive and
      Gram-negative bacterial pathogens. Previously, a library of novel trisubstituted
      benzimidazoles was constructed for high throughput screening, and compounds were
      identified that exhibited potency against M. tuberculosis H37Rv and clinical
      isolates, and were not toxic to Vero cells. A new series of 2-cyclohexyl-5
      acylamino-6-N, N-dimethylaminobenzimidazoles derivatives has been developed based
      on SAR studies. Screening identified compounds with potency against M.
      tuberculosis. A lead compound from this series, SB-P17G-A20, was discovered to
      have an MIC of 0.16 ug/mL and demonstrated efficacy in the TB murine acute model
      of infection based on the reduction of bacterial load in the lungs and spleen by
      1.73 +/- 0.24 Log10 CFU and 2.68 +/- Log10 CFU, respectively, when delivered at
      50 mg/kg by intraperitoneal injection (IP) twice daily (bid). The activity of SB
      P17G-A20 was determined to be concentration dependent and to have excellent
      stability in mouse and human plasma, and liver microsomes. Together, these
      studies demonstrate that SB-P17G-A20 has potency against M. tuberculosis clinical
      strains with varying susceptibility and efficacy in animal models of infection,
      and that trisubstituted benzimidazoles continue to be a platform for the
      development of novel inhibitors with efficacy.

PMID- 24736744
TI  - A multivariate model of stakeholder preference for lethal cat management.
AB  - Identifying stakeholder beliefs and attitudes is critical for resolving
      management conflicts. Debate over outdoor cat management is often described as a
      conflict between two groups, environmental advocates and animal welfare
      advocates, but little is known about the variables predicting differences among
      these critical stakeholder groups. We administered a mail survey to randomly
      selected stakeholders representing both of these groups (n=1,596) in Florida,
      where contention over the management of outdoor cats has been widespread. We used
      a structural equation model to evaluate stakeholder intention to support non
      lethal management. The cognitive hierarchy model predicted that values influenced
      beliefs, which predicted general and specific attitudes, which in turn,
      influenced behavioral intentions. We posited that specific attitudes would
      mediate the effect of general attitudes, beliefs, and values on management
      support. Model fit statistics suggested that the final model fit the data well
      (CFI=0.94, RMSEA=0.062). The final model explained 74% of the variance in
      management support, and positive attitudes toward lethal management (humaneness)
      had the largest direct effect on management support. Specific attitudes toward
      lethal management and general attitudes toward outdoor cats mediated the
      relationship between positive (p<0.05) and negative cat-related impact beliefs
      (p<0.05) and support for management. These results supported the specificity
      hypothesis and the use of the cognitive hierarchy to assess stakeholder intention
      to support non-lethal cat management. Our findings suggest that stakeholders can
      simultaneously perceive both positive and negative beliefs about outdoor cats,
      which influence attitudes toward and support for non-lethal management.

PMID- 24736745
TI  - Identification of the major molecular types of Cryptococcus neoformans and C.
      gattii by Hyperbranched rolling circle amplification.
AB  - The agents of cryptococcosis C. neoformans and C. gattii are important agents of
      meningoencephalitis in immunocompromised and immunocompetent hosts, respectively.
      They are grouped into eight major molecular types, VNI-VNIV for C. neoformans and
      VGI-VGIV for C. gattii. These major molecular types differ in their host range,
      epidemiology, antifungal susceptibility and geographic distribution. To enable a
      rapid identification of the major molecular types and potential hybrids within
      the two species specific probes based on the PLB1 gene in combination with
      hyperbranched rolling circle amplification (HRCA) were developed. HRCA was
      applied to 76 cryptococcal strains, 10 strains each representing the 7 haploid
      major molecular types, 4 VNIII hybrid strains and 2 inter-species hybrid strains.
      All strains were correctly identified to the major molecular type and or hybrid
      type using HRCA alone. To increase the sensitivity a semi-nested PCR step was
      developed, which will enable the identification of the molecular types/hybrids
      directly from clinical samples, harboring a low copy number of DNA (40 copies).
      Thus, HRCA based on the PLB1 locus alone and in combination with a semi-nested
      PCR showed to be a specific and sensitive methodology, with a great potential to
      be used on clinical specimens for the direct diagnosis of the agents of
      cryptococcosis, including hybrid strains, enabling a rapid and patient tailored
      treatment choice of this disease. 

PMID- 24736747
TI  - Metabolomics as a potential chemotaxonomical tool: application in the genus
      Vernonia schreb.
AB  - The taxonomic classification of the genus Vernonia Schreb is complex and, as yet,
      unclear. We here report the use of untargeted metabolomics approaches, followed
      by multivariate analyses methods and a phytochemical characterization of ten
      Vernonia species. Metabolic fingerprints were obtained by accurate mass
      measurements and used to determine the phytochemical similarities and differences
      between species through multivariate analyses approaches. Principal component
      analysis based on the relative levels of 528 metabolites, indicated that the ten
      species could be clustered into four groups. Thereby, V. polyanthes was the only
      species with presence of flavones chrysoeriol-7-O-glycuronyl, acacetin-7-O
      glycuronyl and sesquiterpenes lactones piptocarphin A and piptocarphin B, while
      glaucolide A was detected in both V. brasiliana and V. polyanthes, separating
      these species from the two other species of the Vernonanthura group. Species from
      the Lessingianthus group were unique in showing a positive response in the foam
      test, suggesting the presence of saponins, which could be confirmed by metabolite
      annotation. V. rufogrisea showed a great variety of sesquiterpene lactones,
      placing this species into a separate group. Species within the Chrysolaena group
      were unique in accumulating clovamide. Our results of LC-MS-based profiling
      combined with multivariate analyses suggest that metabolomics approaches, such as
      untargeted LC-MS, may be potentially used as a large-scale chemotaxonomical tool,
      in addition to classical morphological and cytotaxonomical approaches, in order
      to facilitate taxonomical classifications. 

PMID- 24736746
TI  - Genetic and infectious profiles influence cerebrospinal fluid IgG abnormality in
      Japanese multiple sclerosis patients.
AB  - BACKGROUND: Abnormal intrathecal synthesis of IgG, reflected by cerebrospinal
      fluid (CSF) oligoclonal IgG bands (OBs) and increased IgG index, is much less
      frequently observed in Japanese multiple sclerosis (MS) cohorts compared with
      Western cohorts. We aimed to clarify whether genetic and common infectious
      backgrounds influence CSF IgG abnormality in Japanese MS patients. METHODOLOGY:
      We analyzed HLA-DRB1 alleles, and IgG antibodies against Chlamydia pneumoniae,
      Helicobacter pylori, Epstein-Barr virus nuclear antigen (EBNA), and varicella
      zoster virus (VZV) in 94 patients with MS and 367 unrelated healthy controls
      (HCs). We defined CSF IgG abnormality as the presence of CSF OBs and/or increased
      IgG index (>0.658). PRINCIPAL FINDINGS: CSF IgG abnormality was found in 59 of 94
      (62.8%) MS patients. CSF IgG abnormality-positive patients had a significantly
      higher frequency of brain MRI lesions meeting the Barkhof criteria compared with
      abnormality-negative patients. Compared with HCs, CSF IgG abnormality-positive MS
      patients showed a significantly higher frequency of DRB1 1501, whereas CSF IgG
      abnormality-negative patients had a significantly higher frequency of DRB1 0405.
      CSF IgG abnormality-positive MS patients had a significantly higher frequency of
      anti-C. pneumoniae IgG antibodies compared with CSF IgG abnormality-negative MS
      patients, although there was no difference in the frequency of anti-C. pneumoniae
      IgG antibodies between HCs and total MS patients. Compared with HCs, anti-H.
      pylori IgG antibodies were detected significantly less frequently in the total MS
      patients, especially in CSF IgG abnormality-negative MS patients. The frequencies
      of antibodies against EBNA and VZV did not differ significantly among the groups.
      CONCLUSIONS: CSF IgG abnormality is associated with Western MS-like brain MRI
      features. DRB1 1501 and C. pneumoniae infection confer CSF IgG abnormality, while
      DRB1 0405 and H. pylori infection are positively and negatively associated with
      CSF IgG abnormality-negative MS, respectively, suggesting that genetic and
      environmental factors differentially contribute to MS susceptibility according to
      the CSF IgG abnormality status.

PMID- 24736748
TI  - Combined use of the canine adenovirus-2 and DREADD-technology to activate
      specific neural pathways in vivo.
AB  - We here describe a technique to transiently activate specific neural pathways in
      vivo. It comprises the combined use of a CRE-recombinase expressing canine
      adenovirus-2 (CAV-2) and an adeno-associated virus (AAV-hSyn-DIO-hM3D(Gq)
      mCherry) that contains the floxed inverted sequence of the designer receptor
      exclusively activated by designer drugs (DREADD) hM3D(Gq)-mCherry. CAV-2
      retrogradely infects projection neurons, which allowed us to specifically express
      hM3D(Gq)-mCherry in neurons that project from the ventral tegmental area (VTA) to
      the nucleus accumbens (Acb), the majority of which were dopaminergic. Activation
      of hM3D(Gq)-mCherry by intraperitoneal (i.p.) injections of clozapine-N-oxide
      (CNO) leads to increases in neuronal activity, which enabled us to specifically
      activate VTA to Acb projection neurons. The VTA to Acb pathway is part of the
      mesolimbic dopamine system and has been implicated in behavioral activation and
      the exertion of effort. Injections of all doses of CNO led to increases in
      progressive ratio (PR) performance. The effect of the lowest dose of CNO was
      suppressed by administration of a DRD1-antagonist, suggesting that CNO-induced
      increases in PR-performance are at least in part mediated by DRD1-signaling. We
      hereby validate the combined use of CAV-2 and DREADD-technology to activate
      specific neural pathways and determine consequent changes in behaviorally
      relevant paradigms.

PMID- 24736750
TI  - Development of safe and effective RSV vaccine by modified CD4 epitope in G
      protein core fragment (Gcf).
AB  - Respiratory syncytial virus (RSV) is a major cause of respiratory tract infection
      in infants and young children worldwide, but currently no safe and effective
      vaccine is available. The RSV G glycoprotein (RSVG), a major attachment protein,
      is an important target for the induction of protective immune responses during
      RSV infection. However, it has been thought that a CD4+ T cell epitope (a.a. 183
      195) within RSVG is associated with pathogenic pulmonary eosinophilia. To develop
      safe and effective RSV vaccine using RSV G protein core fragment (Gcf), several
      Gcf variants resulting from modification to CD4+ T cell epitope were constructed.
      Mice were immunized with each variant Gcf, and the levels of RSV-specific serum
      IgG were measured. At day 4 post-challenge with RSV subtype A or B, lung viral
      titers and pulmonary eosinophilia were determined and changes in body weight were
      monitored. With wild type Gcf derived from RSV A2 (wtAGcf), although RSV A
      subtype-specific immune responses were induced, vaccine-enhanced disease
      characterized by excessive pulmonary eosinophil recruitment and body weight loss
      were evident, whereas wtGcf from RSV B1 (wtBGcf) induced RSV B subtype-specific
      immune responses without the signs of vaccine-enhanced disease. Mice immunized
      with Th-mGcf, a fusion protein consisting CD4+ T cell epitope from RSV F (F51-66)
      conjugated to mGcf that contains alanine substitutions at a.a. position 185 and
      188, showed higher levels of RSV-specific IgG response than mice immunized with
      mGcf. Both wtAGcf and Th-mGcf provided complete protection against RSV A2 and
      partial protection against RSV B. Importantly, mice immunized with Th-mGcf did
      not develop vaccine-enhanced disease following RSV challenge. Immunization of Th
      mGcf provided protection against RSV infection without the symptom of vaccine
      enhanced disease. Our study provides a novel strategy to develop a safe and
      effective mucosal RSV vaccine by manipulating the CD4+ T cell epitope within RSV
      G protein. 

PMID- 24736749
TI  - Activated macrophage survival is coordinated by TAK1 binding proteins.
AB  - Macrophages play diverse roles in tissue homeostasis and immunity, and
      canonically activated macrophages are critically associated with acute
      inflammatory responses. It is known that activated macrophages undergo cell death
      after transient activation in some settings, and the viability of macrophages
      impacts on inflammatory status. Here we report that TGFbeta- activated kinase
      (TAK1) activators, TAK1-binding protein 1 (TAB1) and TAK1-binding protein 2
      (TAB2), are critical molecules in the regulation of activated macrophage
      survival. While deletion of Tak1 induced cell death in bone marrow derived
      macrophages even without activation, Tab1 or Tab2 deletion alone did not
      profoundly affect survival of naive macrophages. However, in lipopolysaccharide
      (LPS)-activated macrophages, even single deletion of Tab1 or Tab2 resulted in
      macrophage death with both necrotic and apoptotic features. We show that TAB1 and
      TAB2 were redundantly involved in LPS-induced TAK1 activation in macrophages.
      These results demonstrate that TAK1 activity is the key to activated macrophage
      survival. Finally, in an in vivo setting, Tab1 deficiency impaired increase of
      peritoneal macrophages upon LPS challenge, suggesting that TAK1 complex
      regulation of macrophages may participate in in vivo macrophage homeostasis. Our
      results demonstrate that TAB1 and TAB2 are required for activated macrophages,
      making TAB1 and TAB2 effective targets to control inflammation by modulating
      macrophage survival. 

PMID- 24736751
TI  - The contributions of image content and behavioral relevancy to overt attention.
AB  - During free-viewing of natural scenes, eye movements are guided by bottom-up
      factors inherent to the stimulus, as well as top-down factors inherent to the
      observer. The question of how these two different sources of information interact
      and contribute to fixation behavior has recently received a lot of attention.
      Here, a battery of 15 visual stimulus features was used to quantify the
      contribution of stimulus properties during free-viewing of 4 different categories
      of images (Natural, Urban, Fractal and Pink Noise). Behaviorally relevant
      information was estimated in the form of topographical interestingness maps by
      asking an independent set of subjects to click at image regions that they
      subjectively found most interesting. Using a Bayesian scheme, we computed
      saliency functions that described the probability of a given feature to be
      fixated. In the case of stimulus features, the precise shape of the saliency
      functions was strongly dependent upon image category and overall the saliency
      associated with these features was generally weak. When testing multiple features
      jointly, a linear additive integration model of individual saliencies performed
      satisfactorily. We found that the saliency associated with interesting locations
      was much higher than any low-level image feature and any pair-wise combination
      thereof. Furthermore, the low-level image features were found to be maximally
      salient at those locations that had already high interestingness ratings.
      Temporal analysis showed that regions with high interestingness ratings were
      fixated as early as the third fixation following stimulus onset. Paralleling
      these findings, fixation durations were found to be dependent mainly on
      interestingness ratings and to a lesser extent on the low-level image features.
      Our results suggest that both low- and high-level sources of information play a
      significant role during exploration of complex scenes with behaviorally relevant
      information being more effective compared to stimulus features. 

PMID- 24736752
TI  - Imaging. Can FFRCT replace old indices of coronary stenosis severity?
AB  - The NXT trial supports the value of computational fluid dynamics applied to the
      digitally reconstructed coronary tree as a noninvasive method of identifying
      ischaemia-generating stenoses. The results of the study also suggest that old
      indices of angiographic severity used in clinical practice, such as percent
      diameter stenosis, might become obsolete.

PMID- 24736754
TI  - Surgery: Low-dose aspirin and clonidine--no benefit during surgery.

PMID- 24736755
TI  - Biomarkers: hs-cTnT measurement to rule out MI.

PMID- 24736756
TI  - Acute coronary syndromes: Metformin not associated with improved left ventricular
      function after STEMI in patients without diabetes mellitus.

PMID- 24736757
TI  - Device therapy: Defibrillator-based CRT for heart failure.

PMID- 24736759
TI  - Acute coronary syndromes: Aleglitazar trial findings reported.

PMID- 24736758
TI  - Heart transplantation with donation after circulatory determination of death.
AB  - The constant shortage of available organs is a major obstacle and limiting factor
      in heart transplantation; the discrepancy between the number of donors and
      potential recipients leads to waiting-list mortality of 10-12% per year in Europe
      and the USA. If adopted for heart transplantation, donation after circulatory
      determination of death (DCDD) would be expected to improve the availability of
      organs substantially for both adults and children. With DCDD, however, hearts to
      be transplanted undergo a period of warm ischaemia before procurement, which is
      of particular concern because tissue damage occurs rapidly and might be
      sufficient to preclude transplantation. Nonetheless, the heart is able to
      withstand limited periods of warm ischaemia, which could provide a window of
      opportunity for DCDD. Development of clinical approaches specifically for DCDD is
      critical for the exploitation of these organs, because current practices for
      donor heart procurement, evaluation, and storage have been optimized for
      conventional donation after brain death, without consideration of warm ischaemia
      before organ procurement. Establishment of clinical protocols and ethical and
      legal frameworks for DCDD of other organs is underway. This Review provides a
      timely evaluation of the potential for DCDD in heart transplantation.

PMID- 24736761
TI  - Coronary artery disease: Darapladib fails to improve the STABILITY of CAD.

PMID- 24736762
TI  - Valvular disease: Transcatheter aortic valve replacement trials presented at the
      2014 ACC Scientific Sessions.

PMID- 24736764
TI  - Co-expression network analysis of differentially expressed genes associated with
      metastasis in prolactin pituitary tumors.
AB  - The aim of the present study was to construct a co-expression network of
      differently expressed genes (DEGs) in prolactin pituitary (PRL) tumor metastasis.
      The gene expression profile, GSE22812 was downloaded from the Gene Expression
      Omnibus database, and including five non-invasive, two invasive and six
      aggressive-invasive PRL tumor samples. Compared with non-invasive samples, DEGs
      were identified in invasive and aggressive-invasive samples using a limma package
      in R language. The expression values of DEGs were hierarchically clustered. Next,
      Gene Ontology (GO) function enrichment and Kyoto Encyclopedia of Genes and
      Genomes pathway analysis of DEGs were performed via The Database for Annotation,
      Visualization and Integrated Discovery. Finally, gene pairs of DEGs between non
      invasive and aggressive-invasive samples were identified using the Spearman cor(
      ) function in R language. Compared with the non-invasive samples, 61 and 89 DEGs
      were obtained from invasive and aggressive-invasive samples, respectively.
      Cluster analysis showed that four genes were shared by the two samples, including
      upregulated solute carrier family 2, facilitated glucose transporter member 11
      (SLC2A11) and teneurin transmembrane protein 1 (TENM1) and downregulated importin
      7 (IPO7) and chromogranin B (CHGB). In the invasive samples, the most significant
      GO terms responded to cyclic adenosine monophosphate and a glucocorticoid
      stimulus. However, this occurred in the cell cycle, and was in response to
      hormone stimulation in aggressive-invasive samples. The co-expression network of
      DEGs showed different gene pairs and modules, and SLC2A11 and CHGB occurred in
      two co-expression networks within different co-expressed pairs. In the present
      study, the co-expression network was constructed using bioinformatics methods.
      SLC2A11, TENM1, IPO7 and CHGB are hypothesized to be closely associated with
      metastasis of PRL. Furthermore, CHGB and SLC2A11 may be significant in PRL tumor
      progression and serve as molecular biomarkers for PRL tumors. However, further
      investigation is required to confirm the current results. 

PMID- 24736765
TI  - N-terminal pro-B-type natriuretic peptide is inversely associated with metabolic
      syndrome in hypertensive patients.
AB  - BACKGROUND: It has been shown that metabolic syndrome is associated with lower
      levels of plasma N-terminal pro-B-type natriuretic peptide (Nt-proBNP) in the
      general population. However, there is no study about the association between Nt
      proBNP and metabolic syndrome in hypertensive patients. AIM: : To elucidate the
      relationship between Nt-proBNP and components of metabolic syndrome in
      hypertensive patients. METHODS: Fasting blood samples were obtained from 74
      hypertensive patients in our institution. Plasma levels of Nt-proBNP and other
      biochemical data were measured. Metabolic syndrome and its components were
      defined using diagnostic criteria from the International Diabetes Federation.
      RESULTS: Forty-four hypertensive patients met the criteria for metabolic
      syndrome. We found that plasma Nt-proBNP levels were lower in hypertensive
      patients with metabolic syndrome attributable to inverse relationships between Nt
      proBNP and albumin, triglyceride, insulin, homeostasis model assessment of
      insulin resistance (HOMA-IR) and pancreatic beta-cell function (HOMA-beta). We
      further performed a multivariable linear regression analysis. The result showed
      that HOMA-IR is the independent predictor of plasma Nt-proBNP levels in
      hypertensive patients. CONCLUSIONS: Plasma Nt-proBNP levels are inversely
      associated with metabolic syndrome in hypertensive patients. HOMA-IR is the
      independent predictor of Nt-proBNP in hypertensive patients.

PMID- 24736766
TI  - Effect of obstructive sleep apnea treatment on mail-in cognitive function
      screening instrument.
AB  - BACKGROUND: Obstructive sleep apnea syndrome (OSAS) may be associated with
      cognitive impairment (CI). The goal of this study was to evaluate the impact of
      risk factors and continuous positive airway pressure (CPAP) on a screening tool
      for cognitive function. METHODS: The Mail-In Cognitive Function Screening
      Instrument (MCFSI) is a self-administered test designed to identify CI in the
      Alzheimer's Disease Cooperative Study. It was administered to 88 consecutive
      patients with OSAS attending the Medical University of South Carolina Sleep
      Clinic. An MCFSI score >=5 was considered abnormal. RESULTS: Data were analyzed
      on 61 patients after excluding missing and duplicate data. The MCFSI score was
      abnormal in 15 patients (25%). African Americans were more likely to be CPAP
      noncompliant. Female gender and smoking were associated with abnormal MCFSI
      scores. CPAP-compliant patients were more likely to have normal MCFSI scores,
      although the difference was not statistically significant (P = 0.06).
      CONCLUSIONS: CPAP-compliant patients showed a trend toward lower MCFSI scores.
      There may be gender and racial differences in CI related to OSAS, predisposing
      certain groups to worse morbidity. Appropriate treatment and compliance with CPAP
      could improve CI in OSAS. Larger studies with multivariate analyses are needed to
      identify relationships between individual OSAS and CI risk factors.

PMID- 24736767
TI  - Patient understanding and impression of hematology/oncology fellows.
AB  - BACKGROUND: Hematologists/Oncologists spend years of training in a fellowship
      program. At academic centers, patients receiving treatment are often seen by
      fellows. It has not been established what patients understand about fellowship
      training, therefore the purpose of this study was to explore their understanding
      and whether they are content with fellows taking part in their care. METHODS: At
      West Virginia University/Mary Babb Randolph Cancer Center, the authors drafted a
      survey. This anonymous and voluntary survey abstracted basic patient demographic
      data and experience being cared for by fellows and basic knowledge of a
      Hematology/Oncology fellowship. Multiple-choice questions were drafted with 4 to
      6 answer choices with no option for unknown. Surveys were collected over a 3-week
      period in July 2012. Patients were surveyed at outpatient appointments, infusion
      center visits, and laboratory draws. RESULTS: Two hundred twenty-six surveys were
      collected. Statistical analysis was performed and a binomial regression was fit
      to the data. There is evidence that higher levels of education are more likely to
      give correct answers (P = 0.035). Patients who stated that they had not seen a
      fellow or were unsure whether they had seen a fellow were more likely to select
      incorrect answers (P = 0.001). There is no statistical significance
      differentiating between cancer types in likelihood of getting answers correct. Of
      those surveyed, 1.77% felt that they completely understand the role of a fellow
      in their care, whereas 80.45% desired further information about fellows. Only
      2.2% disliked having a fellow involved in their care. CONCLUSIONS: Patients at
      academic centers being seen by Hematology/Oncology fellows appear to have a lack
      of knowledge of a fellow's role and background but have a desire to be educated.
      Educational initiatives can be introduced to teaching institutions to help
      patients better understand the role of a fellow.

PMID- 24736768
TI  - Monitoring training load, recovery-stress state, immune-endocrine responses, and
      physical performance in elite female basketball players during a periodized
      training program.
AB  - This study investigated the effect of a periodized training program on internal
      training load (ITL), recovery-stress state, immune-endocrine responses, and
      physical performance in 19 elite female basketball players. The participants were
      monitored across a 12-week period before an international championship, which
      included 2 overloading and tapering phases. The first overloading phase (fourth
      to sixth week) was followed by a 1-week tapering, and the second overloading
      phase (eighth to 10th week) was followed by a 2-week tapering. ITL (session
      rating of perceived exertion method) and recovery-stress state (RESTQ-76 Sport
      questionnaire) were assessed weekly and bi-weekly, respectively. Pretraining and
      posttraining assessments included measures of salivary IgA, testosterone and
      cortisol concentrations, strength, jumping power, running endurance, and agility.
      Internal training load increased across all weeks from 2 to 11 (p <= 0.05). After
      the first tapering period (week 7), a further increase in ITL was observed during
      the second overloading phase (p <= 0.05). After the second tapering period, a
      decrease in ITL was detected (p <= 0.05). A disturbance in athlete stress
      recovery state was noted during the second overloading period (p <= 0.05), before
      returning to baseline level in end of the second tapering period. The training
      program led to significant improvements in the physical performance parameters
      evaluated. The salivary measures did not change despite the fluctuations in ITL.
      In conclusion, a periodized training program evoked changes in ITL in elite
      female basketball players, which appeared to influence their recovery-stress
      state. The training plan was effective in preparing participants for competition,
      as indicated by improvements in recovery-stress state and physical performance
      after tapering.

PMID- 24736769
TI  - A novel running mechanic's class changes kinematics but not running economy.
AB  - A novel method of running technique instruction, Midstance to Midstance Running
      (MMR), was studied to determine how MMR affected kinematics and running economy
      (RE) of recreational runners. An experimental pre-post randomized groups design
      was used. Participants (n = 18) were recreational runners who ran at least 3 days
      a week and 5 km per run. All testing was performed on a treadmill at 2.8 m.s. The
      intervention group (n = 9) completed 8 weeks of instruction in MMR; the control
      group (n = 9) continued running without instruction. The MMR group showed
      significant decreases in stride length (SL) (p = 0.02) and maximum knee flexion
      velocity in stance (p = 0.01), and a significant increase in stride rate (SR) (p
      = 0.02) after 8 weeks. No significant changes were found in heart rate, rating of
      perceived exertion, or RE. Midstance to Midstance Running was effective in
      changing SR and SL, but was not effective in changing other kinematic variables
      such as foot contact position and maximum knee flexion during swing. Midstance to
      Midstance Running did not affect RE. Evidence suggests that MMR may be an
      appropriate instructional method for recreational runners trying to decrease SL
      and increase SR.

PMID- 24736770
TI  - Effects of resisted sprint training on acceleration with three different loads
      accounting for 5, 12.5, and 20% of body mass.
AB  - The optimal resisted load for sprint training has not been established yet,
      although it has been suggested that a resistance reducing the athlete's velocity
      by more than 10% from unloaded sprinting would entail substantial changes in the
      athlete's sprinting mechanics. This investigation has evaluated the effects of a
      7-week, 14-session, sled-resisted sprint training on acceleration with 3
      different loads according to a % of body mass (BM): low load (LL: 5% BM, n = 7),
      medium load (ML: 12.5% BM, n = 6), and high load (HL: 20% BM, n = 6), in young
      male students. Besides, the effects on untrained exercises: countermovement jump
      (CMJ), loaded vertical jump squat (JS), and full squat (SQ) were analyzed. The 3
      groups followed the same training program consisting in maximal effort sprint
      accelerations with the respective loads assigned. Significant differences between
      groups only occurred between LL and ML in CMJ (p <= 0.05), favoring ML. Paired t
      tests demonstrated statistical improvements in 0-40 m sprint times for the 3
      groups (p <= 0.05), and in 0-20 m (p <= 0.05) and 0-30 m (p < 0.01) sprint times
      for HL. Sprint times in 10-40 m (p < 0.01) and 20-40 m (p <= 0.05) were improved
      in LL. Time intervals in 20-30 m and 20-40 m (p <= 0.05) were statistically
      reduced in ML. As regards, the untrained exercises, CMJ and SQ for ML and HL (p
      <= 0.05) and JS for HL were improved. The results show that depending on the
      magnitude of load used, the related effects will be attained in different phases
      of the 40 m. It would seem that to improve the initial phase of acceleration up
      to 30 m, loads around 20% of BM should be used, whereas to improve high-speed
      acceleration phases, loads around 5-12.5% of BM should be preferred. Moreover,
      sprint-resisted training with ML and HL would enhance vertical jump and leg
      strength in moderately trained subjects.

PMID- 24736771
TI  - Influence of body mass loss on changes in heart rate during exercise in the heat:
      a systematic review.
AB  - The purpose of this review was to compare the changes in heart rate (HR) for
      every 1% change in body mass loss (DeltaBML) in individuals while exercising in
      the heat. PubMed, SPORTDiscus, ERIC, CINAHL, and Scopus were searched from the
      earliest entry to February 2013 using the search terms dehydration, heart rate,
      and exercise in various combinations. Original research articles that met the
      following criteria were included: (a) valid measure of HR, (b) exercise in the
      heat (>26.5 degrees  C [79.7  degrees F]), (c) the level of dehydration reached
      at least 2%, (d) a between-group comparison (a euhydrated group or a graded
      dehydration protocol) was evident, and (e) for rehydration protocols, only oral
      rehydration was considered for inclusion. Twenty articles were included in the
      final analysis. Mean values and SDs for HR and percentage of body mass loss
      immediately after exercise were used for this review. The mean change in HR for
      every 1% DeltaBML was 3 b.min-1. In trials where subjects arrived euhydrated and
      hypohydrated, the mean change in HR for every 1% DeltaBML was 3 and 3 b.min-1,
      respectively. Fixed intensity and variable intensity trials exhibited a mean HR
      change of 4 and 1 b.min-1, respectively. Exercising in the heat while
      hypohydrated (>=2%) resulted in an increased HR after exercise. This increase in
      HR for every 1% DeltaBML exacerbates cardiovascular strain in exercising
      individuals, thus causing decrements in performance. It should be encouraged that
      individuals should maintain an adequate level of hydration to maximize
      performance, especially in the heat.

PMID- 24736772
TI  - Kinetic and Kinematic Analysis for Assessing the Differences in Countermovement
      Jump Performance in Rugby Players.
AB  - Floria, P, Gomez-Landero, LA, Suarez-Arrones, L, and Harrison, AJ. Kinetic and
      kinematic analysis for assessing the differences in countermovement jump
      performance in rugby players. J Strength Cond Res 30(9): 2533-2539, 2016-The aim
      of this study was to ascertain the differences in kinetic and kinematic profiles
      between better and poorer performers of the vertical jump within a homogeneous
      group of trained adults. Fifty rugby players were divided into low scoring (LOW)
      and high scoring (HIGH) groups based on their performance in the vertical jump.
      The force, velocity, displacement, and rate of force development (RFD)-time
      curves were analyzed to determine the differences between groups. The analysis of
      the data showed differences in all the patterns of the ensemble mean curves of
      the HIGH and LOW groups. During the eccentric phase, the differences in the HIGH
      group with respect to the LOW group were lower crouch position, higher downward
      velocity, and higher force and RFD during the braking of the downward movement.
      During the concentric phase, the HIGH group achieved higher upward velocity,
      higher force at the end of phase, and a higher position at takeoff. The higher
      jump performances seem to be related to a more effective stretch-shortening cycle
      function that is characterized by a deeper and faster countermovement with higher
      eccentric forces being applied to decelerate the downward movement leading to
      enhanced force generation during the concentric phase. 

PMID- 24736773
TI  - Maximal strength training improves bone mineral density and neuromuscular
      performance in young adult women.
AB  - -Exercise guidelines highlight maximizing bone mass early in life as a strategy
      to prevent osteoporosis. Which intervention is most effective for this purpose
      remains unclear. This study investigated the musculoskeletal effects of high
      acceleration, maximal strength training (MST), in young adult women. Thirty
      healthy women (22 +/- 2 years) were randomly assigned to a training group (TG)
      and a control group (CG). The TG completed 12 weeks of squat MST, executed at 85
      90% of maximal strength 1 repetition maximum (1RM), emphasizing progressive
      loading and high acceleration in the concentric phase. The CG was encouraged to
      follow the American College of Sports Medicine's exercise guidelines for skeletal
      health. Measurements included bone mineral density (BMD) and body composition by
      dual-energy X-ray absorptiometry, dynamic and isometric rate of force development
      (RFD), and squat 1RM. Serum levels of type 1 collagen amino-terminal propeptide
      (P1NP), type 1 collagen C breakdown products (CTX), and sclerostin were analyzed
      by immunoassays. In the TG, lumbar spine and total hip BMD increased by 2.2 and
      1.0%, whereas serum P1NP increased by 26.2%. Dynamic RFD and 1RM improved by 81.7
      and 97.7%, and isometric RFD improved by 38% at 100 milliseconds. These
      improvements were significantly greater than those observed in the CG. Within the
      CG, dynamic RFD and 1RM increased by 27.2 and 12.9% while no other significant
      changes occurred. These findings suggest that squat MST may serve as a simple,
      time-efficient strategy to optimize peak bone mass in early adulthood.

PMID- 24736774
TI  - Muscle damage of resistance-trained men after two bouts of eccentric bench press
      exercise.
AB  - The present study tested the hypothesis that resistance-trained individuals would
      also show less muscle damage in the second than in the first eccentric exercise
      bout (i.e., repeated bout effect) as shown in untrained individuals. This study
      investigated changes in indirect markers of muscle damage after 2 bouts of free
      weight eccentric exercise performed by 8 resistance-trained men. The participants
      (24.4 +/- 1.2 years) performed 4 sets of 8 eccentric actions (3 seconds for each
      repetition) at 70% of eccentric 1 repetition maximum (1RM) load in a bench press
      exercise with 2 minutes of rest between sets, and repeated the same exercise 2
      weeks later. Bench press 1RM, delayed onset muscle soreness (DOMS) assessed by a
      6-point Likert scale, serum creatine kinase (CK) activity, and plasma
      prostaglandin E2 concentration (PGE2) were measured before and 24, 48, 72, and 96
      hours after the exercise, and the changes were compared between bouts. The
      changes in the variables were smaller (p <= 0.05) after the second than the first
      bout indicated by a smaller decline in 1RM strength (first bout: -10.2 +/- 1.0%
      vs. second bout: -5.7 +/- 1.5%), peak DOMS (3.8 +/- 0.4 vs. 1.7 +/- 0.5), peak CK
      (637.3 +/- 133.3 vs. 305.4 +/- 63.6 IU.L), and peak PGE2 (761.2 +/- 171.0 vs.
      307.2 +/- 48.3 pg.mL). These results show a typical repeated bout effect. Thus,
      it is concluded that the repeated bout effect occurs in resistance-trained
      individuals.

PMID- 24736775
TI  - Effects of different training amplitudes on heart rate and heart rate variability
      in young rowers.
AB  - The aim of this study was to investigate the autonomic nervous system recovery
      and the psychological response as a result of 3 training amplitudes on heart rate
      (HR), heart rate variability (HRV), and rate of perceived exertion (RPE) in
      rowing. Eight young rowers (16.8 +/- 1.4 years) performed, in a randomized
      fashion, 2 sessions of high-intensity interval training, with high and low
      amplitude and a continuous training (CT) session, with the same exercise duration
      (10 minutes) and mean intensity (60% of maximal stroke test). The data of HR,
      HRV, and RPE were collected 5 minutes before, immediately after each session, and
      24 hours later. High amplitude promoted higher impact in maximum HR (p <= 0.05)
      and RPE (p < 0.001) when compared with CT. For the time domain HRV variable,
      there was a statistically significant difference between moments of rest
      (pretraining or post 24 hours) and posttraining in all training sessions.
      Originally, we conclude that training with higher load variation between effort
      and recovery impacts HRV, HR, and RPE with greater intensity, but the younger
      rowers were ready for new training sessions 24 hours after either training
      method. Coaches can use the polarized training method, observing the stimulus
      nature and time required for recovery, because it may be an adequate strategy for
      the development of rower's conditioning.

PMID- 24736776
TI  - Blood ammonia and lactate as markers of muscle metabolites during leg press
      exercise.
AB  - To examine whether blood lactate and ammonia concentrations can be used to
      estimate the functional state of the muscle contractile machinery with regard to
      muscle lactate and adenosine triphosphate (ATP) levels during leg press exercise.
      Thirteen men (age, 34 +/- 5 years; 1 repetition maximum leg press strength 199 +/
      33 kg) performed either 5 sets of 10 repetitions to failure (5*10RF), or 10 sets
      of 5 repetitions not to failure (10*5RNF) with the same initial load (10RM) and
      interset rests (2 minutes) on 2 separate sessions in random order. Capillary
      blood samples were obtained before and during exercise and recovery. Six subjects
      underwent vastus lateralis muscle biopsies at rest, before the first set and
      after the final exercise set. The 5*10RF resulted in a significant and marked
      decrease in power output (37%), muscle ATP content (24%), and high levels of
      muscle lactate (25.0 +/- 8.1 mmol.kg wet weight), blood lactate (10.3 +/- 2.6
      mmol.L), and blood ammonia (91.6 +/- 40.5 MUmol.L). During 10*5RNF no or minimal
      changes were observed. Significant correlations were found between: (a) blood
      ammonia and muscle ATP (r = -0.75), (b) changes in peak power output and blood
      ammonia (r = -0.87) and blood lactate (r = -0.84), and (c) blood and muscle
      lactate (r = 0.90). Blood lactate and ammonia concentrations can be used as
      extracellular markers for muscle lactate and ATP contents, respectively. The
      decline in mechanical power output can be used to indirectly estimate blood
      ammonia and lactate during leg press exercise.

PMID- 24736777
TI  - Hyperlactemia induction modes affect the lactate minimum power and physiological
      responses in cycling.
AB  - The aim of this study was to verify the influence of hyperlactemia and blood
      acidosis induction on lactate minimum intensity (LMI). Twenty recreationally
      trained males who were experienced in cycling (15 cyclists and 5 triathletes)
      participated in this study. The athletes underwent 3 lactate minimum tests on an
      electromagnetic cycle ergometer. The hyperlactemia induction methods used were
      graded exercise test (GXT), Wingate test (WAnT), and 2 consecutive Wingate tests
      (2 * WAnTs). The LMI at 2 * WAnTs (200.3 +/- 25.8 W) was statistically higher
      than the LMI at GXT (187.3 +/- 31.9 W) and WAnT (189.8 +/- 26.0 W), with similar
      findings for blood lactate, oxygen uptake, and pulmonary ventilation at LMI. The
      venous pH after 2 * WAnTs was lower (7.04 +/- 0.24) than in (p <= 0.05) the GXT
      (7.19 +/- 0.05) and WAnT (7.19 +/- 0.05), whereas the blood lactate response was
      higher. In addition, similar findings were observed for bicarbonate concentration
      [HCO3] (2 * WAnTs lower than WAnT; 15.3 +/- 2.6 mmol.L and 18.2 +/- 2.7 mmol.L1,
      respectively) (p <= 0.05). However, the maximal aerobic power and total time
      measured during the incremental phase also did not differ. Therefore, we can
      conclude that the induction mode significantly affects pH, blood lactate, and
      [HCO3] and consequently they alter the LMI and physiological parameters at LMI.

PMID- 24736778
TI  - The effect of wave conditions and surfer ability on performance and the
      physiological response of recreational surfers.
AB  - This study investigated the effects of wave conditions on performance and the
      physiological responses of surfers. After institutional ethical approval 39
      recreational surfers participated in 60 surfing sessions where performance and
      physiological response were measured using global positioning system (GPS) heart
      rate monitors. Using GPS, the percentage time spent in surfing activity
      categories was on average 41.6, 47.0, 8.1, and 3.1% for waiting, paddling,
      riding, and miscellaneous activities, respectively. Ability level of the surfers,
      wave size, and wave period are significantly associated with the physiological,
      ride, and performance parameters during surfing. As the ability level of the
      surfers increases there is a reduction in the relative exercise intensity (e.g.,
      average heart rate as a percentage of laboratory maximum, rpartial = -0.412, p <
      0.01) which is in contrast to increases in performance parameters (e.g., maximum
      ride speed (0.454, p < 0.01). As the wave size increased there were reductions in
      physiological demand (e.g., total energy expenditure rpartial = -0.351, p <=
      0.05) but increases in ride speed and distance measures (e.g., the maximum ride
      speed, 0.454, p < 0.01). As the wave period increased there were increases in
      intensity (e.g., average heart rate as a percentage of laboratory maximum, rp =
      0.490, p < 0.01) and increases in ride speed and distance measures (e.g., the
      maximum ride speed, rpartial = 0.371, p < 0.01). This original study is the first
      to show that wave parameters and surfer ability are significantly associated with
      the physiological response and performance characteristics of surfing.

PMID- 24736779
TI  - Evaluation of a method for nitrotyrosine site identification and relative
      quantitation using a stable isotope-labeled nitrated spike-in standard and high
      resolution fourier transform MS and MS/MS analysis.
AB  - The overproduction of reactive oxygen and nitrogen species (ROS and RNS) can have
      deleterious effects in the cell, including structural and possible activity
      altering modifications to proteins. Peroxynitrite is one such RNS that can result
      in a specific protein modification, nitration of tyrosine residues to form
      nitrotyrosine, and to date, the identification of nitrotyrosine sites in proteins
      continues to be a major analytical challenge. We have developed a method by which
      15N-labeled nitrotyrosine groups are generated on peptide or protein standards
      using stable isotope-labeled peroxynitrite (O15NOO-), and the resulting standard
      is mixed with representative samples in which nitrotyrosine formation is to be
      measured by mass spectrometry (MS). Nitropeptide MS/MS spectra are filtered using
      high mass accuracy Fourier transform MS (FTMS) detection of the nitrotyrosine
      immonium ion. Given that the nitropeptide pair is co-isolated for MS/MS
      fragmentation, the nitrotyrosine immonium ions (at m/z=181 or 182) can be used
      for relative quantitation with negligible isotopic interference at a mass
      resolution of greater than 50,000 (FWHM, full width at half-maximum).
      Furthermore, the standard potentially allows for the increased signal of
      nitrotyrosine-containing peptides, thus facilitating selection for MS/MS in a
      data-dependent mode of acquisition. We have evaluated the methodology in terms of
      nitrotyrosine site identification and relative quantitation using nitrated
      peptide and protein standards.

PMID- 24736780
TI  - Neuroprotective effects of citicoline in in vitro models of retinal
      neurodegeneration.
AB  - In recent years, citicoline has been the object of remarkable interest as a
      possible neuroprotectant. The aim of this study was to investigate if citicoline
      affected cell survival in primary retinal cultures and if it exerted
      neuroprotective activity in conditions modeling retinal neurodegeneration.
      Primary retinal cultures, obtained from rat embryos, were first treated with
      increasing concentrations of citicoline (up to 1000 uM) and analyzed in terms of
      apoptosis and caspase activation and characterized by immunocytochemistry to
      identify neuronal and glial cells. Subsequently, excitotoxic concentration of
      glutamate or High Glucose-containing cell culture medium (HG) was administered as
      well-known conditions modeling neurodegeneration. Glutamate or HG treatments were
      performed in the presence or not of citicoline. Neuronal degeneration was
      evaluated in terms of apoptosis and loss of synapses. The results showed that
      citicoline did not cause any damage to the retinal neuroglial population up to
      1000 uM. At the concentration of 100 uM, it was able to counteract neuronal cell
      damage both in glutamate- and HG-treated retinal cultures by decreasing
      proapoptotic effects and contrasting synapse loss. These data confirm that
      citicoline can efficiently exert a neuroprotective activity. In addition, the
      results suggest that primary retinal cultures, under conditions inducing
      neurodegeneration, may represent a useful system to investigate citicoline
      neuroprotective mechanisms. 

PMID- 24736781
TI  - Maternal high folic acid supplement promotes glucose intolerance and insulin
      resistance in male mouse offspring fed a high-fat diet.
AB  - Maternal nutrition may influence metabolic profiles in offspring. We aimed to
      investigate the effect of maternal folic acid supplement on glucose metabolism in
      mouse offspring fed a high-fat diet (HFD). Sixty C57BL/6 female mice were
      randomly assigned into three dietary groups and fed the AIN-93G diet containing 2
      (control), 5 (recommended folic acid supplement, RFolS) or 40 (high folic acid
      supplement, HFolS) mg folic acid/kg of diet. All male offspring were fed HFD for
      eight weeks. Physiological, biochemical and genetic variables were measured.
      Before HFD feeding, developmental variables and metabolic profiles were
      comparable among each offspring group. However, after eight weeks of HFD feeding,
      the offspring of HFolS dams (Off-HFolS) were more vulnerable to suffer from
      obesity (p=0.009), glucose intolerance (p<0.001) and insulin resistance
      (p<0.001), compared with the controls. Off-HFolS had reduced serum adiponectin
      concentration, accompanied with decreased adiponectin mRNA level but increased
      global DNA methylation level in white adipose tissue. In conclusion, our results
      suggest maternal HFolS exacerbates the detrimental effect of HFD on glucose
      intolerance and insulin resistance in male offspring, implying that HFolS during
      pregnancy should be adopted cautiously in the general population of pregnant
      women to avoid potential deleterious effect on the metabolic diseases in their
      offspring.

PMID- 24736782
TI  - GPC1 regulated by miR-96-5p, rather than miR-182-5p, in inhibition of pancreatic
      carcinoma cell proliferation.
AB  - To determine the relationships between miR-96-5p/-182-5p and GPC1 in pancreatic
      cancer (PC), we conducted the population and in vitro studies. We followed 38
      pancreatic cancer patients, measured and compared the expression of miR-96-5p/
      182-5p, GPC1, characteristics and patients' survival time of different miR-96-5p/
      182-5p expression levels in PC tissues. In an in vitro study, we investigated the
      proliferation, cycle and apotosis in cells transfected with mimics/inhibitors of
      the two miRNAs, and determine their effects on GPC1 by dual-luciferase assay. In
      the follow-up study, we found that the expressions of miR-96-5p/-182-5p were
      lower/higher in PC tissues; patients with lower/higher levels of miR-96-5p/-182
      5p suffered poorer characteristics and decreased survival time. In the in vitro
      study, the expressions of miR-96-5p/-182-5p were different in cells.
      Proliferation of cells transfected with miR-96-5p mimics/inhibitors was
      lower/higher in Panc-1/BxPC-3; when transfected with miR-182-5p
      mimics/inhibitors, proliferation of cells were higher/lower in AsPC-1/Panc-1. In
      a cell cycle study, panc-1 cells transfected with miR-96-5p mimics was arrested
      at G0/G1; BxPC-3 cells transfected with miR-96-5p inhibitors showed a
      significantly decrease at G0/G1; AsPC-1 cells transfected with miR-182-5p mimics
      was arrested at S; Panc-1 cells transfected with miR-182-5p inhibitors showed a
      decrease at S. MiR-96-5p mimics increased the apoptosis rate in Panc-1 cells, and
      its inhibitors decreased the apoptosis rate in BxPC-3. Dual luciferase assay
      revealed that GPC1 was regulated by miR-96-5p, not -182-5p. We found that miR-96
      5p/-182-5p as good markers for PC; miR-96-5p, rather than -182-5p, inhibits GPC1
      to suppress proliferation of PC cells. 

PMID- 24736783
TI  - Isolation of the autoinducer-quenching strain that inhibits LasR in Pseudomonas
      aeruginosa.
AB  - Quorum sensing (QS) has been recognized as a general phenomenon in microorganisms
      and plays an important role in many pathogenic bacteria. In this report, we used
      the Agrobacterium tumefaciens biosensor strain NT1 to rapidly screen for
      autoinducer-quenching inhibitors from bacteria. After initial screening 5389
      isolates obtained from land and beach soil, 53 putative positive strains were
      identified. A confirmatory bioassay was carried out after concentrating the
      putative positive culture supernatant, and 22 strains were confirmed to have anti
      LasR activity. Finally, we determined the strain JM2, which could completely
      inhibit biofilm formation of Pseudomonas aeruginosa PAO1, belonged to the genus
      Pseudomonas by analysis of 16S rDNA. Partially purified inhibitor factor(s) F5
      derived from culture supernatants specifically inhibited LasR-controlled elastase
      and protease in wild type P. aeruginosa PAO1 by 68% and 73%, respectively,
      without significantly affecting growth; the rhl-controlled pyocyanin and
      rhamnolipids were inhibited by 54% and 52% in the presence of 100 ug/mL of F5.
      The swarming motility and biofilm of PAO1 were also inhibited by F5. Real time RT
      PCR on samples from 100 ug/mL F5-treated P. aeruginosa showed downregulation of
      autoinducer synthase (LasRI and rhlI) and cognate receptor (lasR and rhlR) genes
      by 50%, 28%, 48%, and 29%, respectively. These results provide compelling
      evidence that the F5 inhibitor(s) interferes with the las system and
      significantly inhibits biofilm formation. 

PMID- 24736784
TI  - Flying the nest: male dispersal and multiple paternity enables extrafamilial
      matings for the invasive bark beetle Dendroctonus micans.
AB  - There is an evolutionary trade-off between the resources that a species invests
      in dispersal versus those invested in reproduction. For many insects,
      reproductive success in patchily-distributed species can be improved by sibling
      mating. In many cases, such strategies correspond to sexual dimorphism, with
      males-whose reproductive activities can take place without dispersal-investing
      less energy in development of dispersive resources such as large body size and
      wings. This dimorphism is particularly likely when males have little or no chance
      of mating outside their place of birth, such as when sperm competition precludes
      successful fertilisation in females that have already mated. The economically
      important bark beetle pest species Dendroctonus micans (Coleoptera:
      Curculionidae, Scolytinae) has been considered to be exclusively sibling-mating,
      with 90% of females having already mated with their brothers by emergence. The
      species does not, however, show strong sexual dimorphism; males closely resemble
      females, and have been observed flying through forests. We hypothesised that this
      lack of sexual dimorphism indicates that male D. micans are able to mate with
      unrelated females, and to sire some or all of their offspring, permitting
      extrafamilial reproduction. Using novel microsatellite markers, we carried out
      cross-breeding laboratory experiments and conducted paternity analyses of
      resulting offspring. Our results demonstrate that a second mating with a less
      related male can indeed lead to some offspring being sired by the latecomer, but
      that most are sired by the first, sibling male. We discuss these findings in the
      context of sperm competition versus possible outbreeding depression. 

PMID- 24736785
TI  - Insights into the history of a bacterial group II intron remnant from the genomes
      of the nitrogen-fixing symbionts Sinorhizobium meliloti and Sinorhizobium
      medicae.
AB  - Group II introns are self-splicing catalytic RNAs that act as mobile
      retroelements. In bacteria, they are thought to be tolerated to some extent
      because they self-splice and home preferentially to sites outside of functional
      genes, generally within intergenic regions or in other mobile genetic elements,
      by mechanisms including the divergence of DNA target specificity to prevent
      target site saturation. RmInt1 is a mobile group II intron that is widespread in
      natural populations of Sinorhizobium meliloti and was first described in the GR4
      strain. Like other bacterial group II introns, RmInt1 tends to evolve toward an
      inactive form by fragmentation, with loss of the 3' terminus. We identified
      genomic evidence of a fragmented intron closely related to RmInt1 buried in the
      genome of the extant S. meliloti/S. medicae species. By studying this intron, we
      obtained evidence for the occurrence of intron insertion before the divergence of
      ancient rhizobial species. This fragmented group II intron has thus existed for a
      long time and has provided sequence variation, on which selection can act,
      contributing to diverse genetic rearrangements, and to generate pan-genome
      divergence after strain differentiation. The data presented here suggest that
      fragmented group II introns within intergenic regions closed to functionally
      important neighboring genes may have been microevolutionary forces driving
      adaptive evolution of these rhizobial species. 

PMID- 24736787
TI  - Adsorption of tetracycline to nano-NiO: the effect of co-existing Cu(ii) ions and
      environmental implications.
AB  - Nano-sized nickel oxide (nano-NiO) is a new nanomaterial that has shown great
      promise in many areas of application. Understanding its environmental fate and
      effects is critical for minimizing the potential environmental implications of
      this new material due to incidental and accidental releases in the future. In
      this study, we observed strong adsorption of tetracycline to nano-NiO and found
      that the adsorption affinity can be further enhanced by Cu(ii) ions - the
      observed distribution coefficient (Kd) values are 10(3.1) to 10(4.2) L kg(-1) in
      the absence of Cu(ii) and 10(3.0) to 10(5.5) L kg(-1) in the presence of Cu(ii);
      such adsorption affinities are even comparable to those of tetracycline to
      carbonaceous materials. The strong adsorptive affinities of nano-NiO for
      tetracycline are likely attributable to several mechanisms, including surface
      complexation, cation exchange, and electrostatic attraction. As a strong
      complexing agent, Cu(ii) can significantly enhance adsorption of tetracycline by
      serving as a bridging agent between tetracycline and nano-NiO. The findings of
      this study have important implications for the risk assessment of engineered
      nanomaterials - in aquatic environments nano-NiO (and likely other metal oxide
      nanomaterials) can strongly adsorb tetracycline antibiotics, resulting in the
      changes of environmental risks of the metal oxide nanomaterials and/or
      bioavailability of the adsorbed contaminants. 

PMID- 24736786
TI  - Genome-wide analysis reveals the ancient and recent admixture history of East
      African Shorthorn Zebu from Western Kenya.
AB  - The Kenyan East African zebu cattle are valuable and widely used genetic
      resources. Previous studies using microsatellite loci revealed the complex
      history of these populations with the presence of taurine and zebu genetic
      backgrounds. Here, we estimate at genome-wide level the genetic composition and
      population structure of the East African Shorthorn Zebu (EASZ) of western Kenya.
      A total of 548 EASZ from 20 sub-locations were genotyped using the Illumina
      BovineSNP50 v. 1 beadchip. STRUCTURE analysis reveals admixture with Asian zebu,
      African and European taurine cattle. The EASZ were separated into three
      categories: substantial (?12.5%), moderate (1.56%<X<12.5%) and non-introgressed
      (?1.56%) according to the European taurine genetic proportion. The non-European
      taurine introgressed animals (n=425) show an unfluctuating zebu and taurine
      ancestry of 0.84+/-0.009 s.d. and 0.16+/-0.009 s.d., respectively, with
      significant differences in African taurine (AT) and Asian zebu backgrounds across
      chromosomes (P<0.0001). In contrast, no such differences are observed for the
      European taurine ancestry (P=0.1357). Excluding European introgressed animals,
      low and nonsignificant genetic differentiation and isolation by distance are
      observed among sub-locations (Fst=0.0033, P=0.09; r=0.155, P=0.07). Following a
      short population expansion, a major reduction in effective population size (Ne)
      is observed from approximately 240 years ago to present time. Our results support
      ancient zebu * AT admixture in the EASZ population, subsequently shaped by
      selection and/or genetic drift, followed by a more recent exotic European cattle
      introgression. 

PMID- 24736792
TI  - Bacterial physiology: a metabolic milieu.

PMID- 24736794
TI  - A versatile framework for microbial engineering using synthetic non-coding RNAs.
AB  - Synthetic non-coding RNAs have emerged as a versatile class of molecular devices
      that have a diverse range of programmable functions, including signal sensing,
      gene regulation and the modulation of molecular interactions. Owing to their
      small size and the central role of Watson-Crick base pairing in determining their
      structure, function and interactions, several distinct types of synthetic non
      coding RNA regulators that are functional at the DNA, mRNA and protein levels
      have been experimentally characterized and computationally modelled. These
      engineered devices can be incorporated into genetic circuits, enabling the more
      efficient creation of complex synthetic biological systems. In this Review, we
      summarize recent progress in engineering synthetic non-coding RNA devices and
      their application to genetic and cellular engineering in a broad range of
      microorganisms. 

PMID- 24736797
TI  - Composition and sources of fine particulate matter across urban and rural sites
      in the Midwestern United States.
AB  - The composition and sources of fine particulate matter (PM2.5) were investigated
      in rural and urban locations in Iowa, located in the agricultural and industrial
      Midwestern United States, from April 2009 to December 2012. Major chemical
      contributors to PM2.5 mass were sulfate, nitrate, ammonium, and organic carbon.
      Non-parametric statistical analyses demonstrated that the two rural sites had
      significantly enhanced levels of crustal materials (Si, Al) driven by
      agricultural activities and unpaved roads. Meanwhile, the three urban areas had
      enhanced levels of secondary aerosols (nitrate, sulfate, and ammonium) and
      combustion products (elemental carbon). The Davenport site had significantly
      higher levels of PM2.5 and trace metals (Fe, Pb, Zn), demonstrating the important
      local impact of industrial point sources on air quality. Sources of PM2.5 were
      evaluated by using the multi-variant positive matrix factorization (PMF) source
      apportionment model. For each individual site, seven to nine factors were
      identified: secondary sulfate (accounting for 29-30% of PM2.5), secondary nitrate
      (17-24%), biomass burning (9-21%), gasoline combustion (6-16%), diesel combustion
      (3-9%), dust (6-11%), industry (0.4-5%) and winter salt (2-6%). Source
      contributions demonstrated a clear urban enhancement in PM2.5 from gasoline
      engines (by a factor of 1.14) and diesel engines (by a factor of 2.3), which is
      significant due to the well-documented negative health impacts of vehicular
      emissions. This study presents the first source apportionment results from the
      state of Iowa and is broadly applicable to understanding the differences in
      anthropogenic and natural sources in the urban-rural continuum of particle air
      pollution. 

PMID- 24736798
TI  - Parental inconsistency, impulsive choice and neural value representations in
      healthy adolescents.
AB  - A well-characterized potential marker for addiction is impulsive choice, stably
      measured by delay discounting (DD) paradigms. While genetic influences partly
      account for inter-individual variance in impulsivity, environmental factors such
      as parenting practices may have an important role. The present study investigates
      how inconsistent fulfillment of delayed reward promises impacts on DD. A combined
      correlational and experimental functional magnetic resonance imaging (fMRI)
      design was performed in a sample of 48 healthy adolescents (13-15 years). More
      specifically, neural activation during a DD task was investigated at two
      assessment points (T0 and T1). Adolescents' self-reports of parenting and
      substance use were assessed at T0. Between assessment points, we experimentally
      varied the reliability of delayed reward promises, measuring the impact of this
      intervention on DD and neural value processing at T1. In the correlational part,
      same-sex parent reward inconsistency was associated with steeper DD and an
      attenuated subjective value (SV) representation in the nucleus accumbens (NAcc)
      and ventromedial prefrontal cortex (vmPFC). Steeper DD was in turn associated
      with alcohol use during the past year. In the experimental part, the reward
      inconsistency manipulation resulted in an attenuation of the NAcc SV
      representation, similar to the parental inconsistency effect. Together, our
      correlational and experimental findings raise new light on how parents may
      influence their children's degree of impulsivity, making parenting a potential
      target in addiction prevention. 

PMID- 24736795
TI  - Biotechnological domestication of pseudomonads using synthetic biology.
AB  - Much of contemporary synthetic biology research relies on the use of bacterial
      chassis for plugging-in and plugging-out genetic circuits and new-to-nature
      functionalities. However, the microorganisms that are the easiest to manipulate
      in the laboratory are often suboptimal for downstream industrial applications,
      which can involve physicochemical stress and harsh operating conditions. In this
      Review, we advocate the use of environmental Pseudomonas strains as model
      organisms that are pre-endowed with the metabolic, physiological and stress
      endurance traits that are demanded by current and future synthetic biology and
      biotechnological needs. 

PMID- 24736799
TI  - Antidepressants differentially related to 1,25-(OH)2 vitamin D3 and 25-(OH)
      vitamin D3 in late-life depression.
AB  - A low plasma 25-OH vitamin D3 level is a universal risk factor for a wide range
      of diseases and has also been implicated in late-life depression. It is currently
      unknown whether the biologically active form of vitamin D, that is, 1,25-(OH)2
      vitamin D3, is also decreased in late-life depression, or whether vitamin D
      levels correlate with specific depression characteristics. We determined plasma
      25-OH vitamin D3, 1,25-(OH)2 vitamin D3 and parathormone levels in 355 depressed
      older persons and 124 non-depressed comparison subjects (age 60 years).
      Psychopathology was established with the Composite International Diagnostic
      Interview 2.1, together with potential confounders and depression characteristics
      (severity, symptom profile, age of onset, recurrence, chronicity and
      antidepressant drug use). Adjusted for confounders, depressed patients had
      significantly lower levels of 25-OH vitamin D33 (Cohen's d =0.28 (95% confidence
      interval: 0.07-0.49), P=0.033) as well as 1,25-(OH)2 vitamin D3 (Cohen's d =0.48
      (95% confidence interval: 0.27-0.70), P<0.001) than comparison subjects. Of all
      depression characteristics tested, only the use of tricyclic antidepressants
      (TCAs) was significantly correlated with lower 1,25-(OH)2 vitamin D3 levels
      (Cohen's d =0.86 (95% confidence interval: 0.53-1.19), P<0.001), but not its
      often measured precursor 25-OH vitamin D3. As vitamin D levels were significantly
      lower after adjustment for confounders, vitamin D might have an aetiological role
      in late-life depression. Differences between depressed and non-depressed subjects
      were largest for the biologically active form of vitamin D. The differential
      impact of TCAs on 25-OH vitamin D3 and 1,25-(OH)2 vitamin D3 levels suggests
      modulation of 1-alpha-hydroxylase and/or 24-hydroxylase, which may in turn have
      clinical implications for biological ageing mechanisms in late-life depression.

PMID- 24736800
TI  - Saikosaponin-d inhibits proliferation of DU145 human prostate cancer cells by
      inducing apoptosis and arresting the cell cycle at G0/G1 phase.
AB  - Saikosaponin-d (SSd), a triterpene saponin compound derived from Bupleurum radix,
      has been shown to have a cytotoxic effect on various cancer cell lines. However,
      its effect on prostate cancer cells has remained unexplored. The present study
      reports the apoptosis-inducing effect of SSd on the DU145 human prostate
      carcinoma cell line. Treatment with SSd inhibited DU145 cell proliferation in a
      concentration-dependent manner. Flow cytometric analysis showed that SSd
      inhibited the proliferation of DU145 cells by induction of apoptosis and cell
      cycle arrest at G0/G1 phase. Further mechanistic experiments demonstrated that
      SSd arrested the cell cycle at G0/G1 phase via upregulation of p53 and p21 and
      induced apoptosis by modulating B-cell lymphoma 2 family proteins, dissipation of
      the mitochondrial membrane potential, release of cytochrome c into the cytosol
      and activation of caspase-3. In conclusion the present study indicated that SSd
      induced apoptosis in DU145 cells by the intrinsic apoptotic pathway. Therefore,
      SSd may become a leading candidate drug for the therapy of prostate carcinoma. 

PMID- 24736801
TI  - Psychometric properties of the Dependence Scale in large randomized clinical
      trials of patients with mild and moderate Alzheimer's disease.
AB  - OBJECTIVE: The need for assistance from others is a hallmark concern in
      Alzheimer's disease (AD). The psychometric properties of the Dependence Scale
      (DS) for measuring treatment benefit were investigated in large randomized
      clinical trials of patients with mild to moderate AD. METHODS: Reliability,
      validity, and responsiveness of the DS were examined. Path models appraised
      relationships and distinctiveness of key AD measures. The responder definition
      was empirically derived. RESULTS: Generally acceptable reliability (alpha >=
      .65), significant (P < .001) known-groups tests, and moderate to strong
      correlations (r >= .31) confirmed the DS psychometric properties. Path models
      supported relationships and distinctiveness of key AD measures. A DS change of <=
      1 point for patients with limited home care and <= 2 points for patients with
      assisted living care best described stability of the level of dependence on
      caregivers. CONCLUSION: The DS is a psychometrically robust measure in mild to
      moderate AD. The empirically derived responder definition aids in the
      interpretation of DS change.

PMID- 24736802
TI  - Chemical sensing of neurotransmitters.
AB  - In the past few decades, the development of chemosensors for neurotransmitters
      has emerged as a research area of significant importance, which attracted a
      tremendous amount of attention due to its high sensitivity and rapid response.
      This current review focuses on various neurotransmitter detection based on
      fluorescent or colorimetric spectrophotometry published for the last 12 years,
      covering biogenic amines (dopamine, epinephrine, norepinephrine, serotonin,
      histamine and acetylcholine), amino acids (glutamate, aspartate, GABA, glycine
      and tyrosine), and adenosine. 

PMID- 24736803
TI  - MicroRNAs play a role in chondrogenesis and osteoarthritis (review).
AB  - Osteoarthritis (OA) is one of the most widespread degenerative joint diseases
      affecting the elderly. Research into the regulatory mechanisms underlying the
      pathogenesis of OA is therefore warranted, and over the past decade, there has
      been an increased focus on the functional role of microRNAs (miRNAs or miRs). In
      this systematic review, we aimed to review the evidence implicating miRNAs in the
      pathogenesis of chondrogenesis and OA. Systematic reviews of PubMed and Embase
      were performed to search for studies using strings of miRNAs, non-coding RNAs,
      cartilage, chondrocytes, chondrogenesis, chondrocytogenesis and OA. The
      identified studies were retrieved, and the references provided were searched. The
      selected studies were required to focus on the role of miRNAs in chondrogenesis
      and OA. The results of this review indicated that more than 25 miRNAs have been
      implicated in chondrogenesis and OA. In particular, chondrocytogenesis,
      chondrogenic differentiation, chondrocyte proliferation, chondrocyte hypertrophy,
      endochondral ossification, and proteolytic enzyme regulation are targeted or
      facilitated by more than 1 miRNA. To date, limited efforts have been performed to
      evaluate translational applications for this knowledge. Novel therapeutic
      strategies have been developed and are under investigation to selectively
      modulate miRNAs, which could potentially enable personalized OA therapy. miRNAs
      appear to be important modulators of chondrogenesis and OA. Their expression is
      frequently altered in OA, and many are functionally implicated in the
      pathogenesis of the disease. The translational roles and therapeutic potential of
      miRNAs remains to be evaluated.

PMID- 24736804
TI  - Magnetically controllable 3D microtissues based on magnetic microcryogels.
AB  - Microtissues on the scale of several hundred microns are a promising cell culture
      configuration resembling the functional tissue units in vivo. In contrast to
      conventional cell culture, handling of microtissues poses new challenges such as
      medium exchange, purification and maintenance of the microtissue integrity. Here,
      we developed magnetic microcryogels to assist microtissue formation with enhanced
      controllability and robustness. The magnetic microcryogels were fabricated on
      chip by cryogelation and micro-molding which could endure extensive external
      forces such as fluidic shear stress during pipetting and syringe injection. The
      magnetically controllable microtissues were applied to constitute a novel
      separable 3D co-culture system realizing functional enhancement of the hepatic
      microtissues co-cultured with the stromal microtissues and easy purification of
      the hepatic microtissues for downstream drug testing. The magnetically
      controllable microtissues with pre-defined shapes were also applied as building
      blocks to accelerate the tissue assembly process under magnetic force for bottom
      up tissue engineering. Finally, the magnetic microcryogels could be injected in
      vivo as cell delivery vehicles and tracked by MRI. The injectable magnetic
      microtissues maintained viability at the injection site indicating good retention
      and potential applications for cell therapy. The magnetic microcryogels are
      expected to significantly promote the microtissues as a promising cellular
      configuration for cell-based applications such as in drug testing, tissue
      engineering and regenerative therapy. 

PMID- 24736805
TI  - [Operative therapy of abdominal and retroperitoneal sarcoma].
AB  - Retroperitoneal soft tissue sarcomas are characterized by a high rate of local
      recurrence. Complete tumor resection is the only potentially curative therapeutic
      option. The concept of a systematic compartmental resection is to remove the
      tumor en bloc with a margin of uninvolved tissue and organs. This is frequently
      only achieved by multivisceral resection which often includes kidney, colon,
      pancreas and parts of the diaphragm or the psoas muscle. The adoption of such a
      policy of multivisceral organ resection improves the proportion of curative
      resections and, ultimately, results in lower local recurrence rates. The present
      article comprehensively describes the operative procedures, perioperative
      treatment and the oncological results of surgery for retroperitoneal sarcomas.
      The role of surgery in oncological treatment plans and the importance of
      specialized centres are outlined in detail. 

PMID- 24736806
TI  - Bone morphogenetic protein-4: a novel therapeutic target for pathological cardiac
      hypertrophy/heart failure.
AB  - Bone morphogenetic protein-4 (BMP4) is a member of the bone morphogenetic protein
      family which plays a key role in the bone formation and embryonic development. In
      addition to these predominate and well-studied effects, the growing evidences
      highlight BMP4 as an important factor in cardiovascular diseases, such as
      hypertension, pulmonary hypertension and valve disease. Our recent works
      demonstrated that BMP4 mediated cardiac hypertrophy, apoptosis, fibrosis and ion
      channel remodeling in pathological cardiac hypertrophy. In this review, we
      discussed the role of BMP4 in pathological cardiac hypertrophy, as well as the
      recent advances about BMP4 in cardiovascular diseases closely related to
      pathological cardiac hypertrophy/heart failure. We put forward that BMP4 is a
      novel therapeutic target for pathological cardiac hypertrophy/heart failure.

PMID- 24736807
TI  - The marine-derived sipholenol A-4-O-3',4'-dichlorobenzoate inhibits breast cancer
      growth and motility in vitro and in vivo through the suppression of Brk and FAK
      signaling.
AB  - Sipholenol A is a natural sipholane triterpenoid isolated from the Red Sea
      sponge, Callyspongia siphonella. Previous studies showed the antimigratory and
      antiproliferative activities of the semisynthetic sipholenol A esters against
      breast cancer cell lines. This study investigated the effects of sipholenol A-4-O
      3',4'-dichlorobenzoate (SPA) on the growth, migration and invasion of diverse
      human breast cancer cells. Results showed that SPA inhibited the growth of the
      human breast cancer cells, MDA-MB-231, MCF-7, BT-474 and T-47D, in a dose
      dependent manner. Immunofluorescent analysis showed that SPA significantly
      reduced Ki-67-positive cells in MDA-MB-231 cells. Flow cytometry and Western blot
      analyses revealed that SPA treatment suppressed MDA-MB-231 cell growth by
      inducing cell cycle arrest at the G1 phase. In addition, SPA suppressed breast
      cancer cell migration, invasion and decreased Brk and FAK activation in a dose
      dependent manner. Molecular docking study suggested a perfect fitting at the
      FAK's FERM domain, inhibiting the main autophosphorylation site, Y397, which was
      further confirmed by Western blot analysis. Most known small molecule FAK
      inhibitors target the kinase domain, creating several off-target side effects.
      The in vivo studies showed that SPA treatment suppressed breast tumor growth and
      Ki-67, CD31, p-Brk and p-FAK expression in orthotopic breast cancer in nude mice.
      In conclusion, SPA inhibited the growth, invasion and migration of breast cancer
      cells possibly via deactivating Brk and FAK signaling, suggesting good potential
      for therapeutic use to control invasive breast cancer. 

PMID- 24736808
TI  - Simulations of transcatheter aortic valve implantation: implications for aortic
      root rupture.
AB  - Aortic root rupture is one of the most severe complications of transcatheter
      aortic valve implantation (TAVI). The mechanism of this adverse event remains
      mostly unknown. The purpose of this study was to obtain a better understanding of
      the biomechanical interaction between the tissue and stent for patients with a
      high risk of aortic rupture. We simulated the stent deployment process of three
      TAVI patients with high aortic rupture risk using finite element method. The
      first case was a retrospective analysis of an aortic rupture case, while the
      other two cases were prospective studies, which ended with one canceled procedure
      and one successful TAVI. Simulation results were evaluated for the risk of aortic
      root rupture, as well as coronary artery occlusion, and paravalvular leak. For
      Case 1, the simulated aortic rupture location was the same as clinical
      observations. From the simulation results, it can be seen that the large
      calcified spot on the interior of the left coronary sinus between coronary ostium
      and the aortic annulus was pushed by the stent, causing the aortic rupture. For
      Case 2 and Case 3, predicated results from the simulations were presented to the
      clinicians at multidisciplinary pre-procedure meetings; and they were in
      agreement with clinician's observations and decisions. Our results indicated that
      the engineering analysis could provide additional information to help clinicians
      evaluate complicated, high-risk aortic rupture cases. Since a systematic study of
      a large patient cohort of aortic rupture is currently not available (due to the
      low occurrence rate) to clearly understand underlying rupture mechanisms, case-by
      case engineering analysis is recommended for evaluating patient-specific aortic
      rupture risk. 

PMID- 24736809
TI  - Potential of cross-priming amplification and DNA-based lateral-flow strip
      biosensor for rapid on-site GMO screening.
AB  - The requirement to monitor the presence of genetically modified organisms (GMO)
      in a variety of marked products has generated an increasing demand for reliable,
      rapid, and time and cost-effective analytical methods. Here we report an on-site
      method for rapid detection of cauliflower mosaic virus promoter (CaMV 35S), a
      common element present in most GMO, using cross-priming amplification (CPA)
      technology. Detection was achieved using a DNA-based contamination-proof strip
      biosensor. The limit of detection was 30 copies for the pBI121 plasmid containing
      the CaMV 35S gene. The certified reference sample of GM maize line MON810 was
      detectable even at the low relative mass concentration of 0.05%. The developed
      CPA method had high specificity for the CaMV 35S gene, as compared with other GM
      lines not containing this gene and non-GM products. The method was further
      validated using nine real-world samples, and the results were confirmed by real
      time PCR analysis. Because of its simplicity, rapidity, and high sensitivity,
      this method of detecting the CaMV 35S gene has great commercial prospects for
      rapid GMO screening of high-consumption food and agriculture products.

PMID- 24736811
TI  - Reining in patient and individual choice.

PMID- 24736810
TI  - Effects of heat stress on the gene expression of nutrient transporters in the
      jejunum of broiler chickens (Gallus gallus domesticus).
AB  - In broiler chickens, heat stress disrupts nutrient digestion and absorption.
      However, the underlying molecular mechanism is not clearly understood. Hence, to
      investigate the effects of high ambient temperatures on the expression levels of
      nutrient transporters in the jejunum of broiler chickens, seventy-two 35-day-old
      male broiler chickens with similar body weights were randomly allocated into two
      groups: control (24 +/- 1  degrees C) and heat-stressed (32 +/- 1  degrees C).
      The chickens in the heat-stressed group were exposed to 10 h of heat daily from
      08:00 to 18:00 and then raised at 24 +/- 1  degrees C. The rectal temperature and
      feed intake of the chickens were recorded daily. After 7 days, nine chickens per
      group were sacrificed by exsanguination, and the jejunum was collected. The
      results show that heat exposure significantly decreased the feed intake and
      increased the rectal temperature of the broiler chickens. The plasma
      concentrations of uric acid and triglyceride significantly increased and
      decreased, respectively, in the heat-stressed group. No significant differences
      in the levels of plasma glucose, total amino acids, and very low-density
      lipoprotein were observed between the heat-stressed and control groups. However,
      the plasma concentration of glucose tended to be higher (P = 0.09) in the heat
      stressed group than in the control group. Heat exposure did not significantly
      affect the mRNA levels of Na(+)-dependent glucose transporter 1 and amino acid
      transporters y + LAT1, CAT1, r-BAT, and PePT-1. However, the expression levels of
      GLUT-2, FABP1, and CD36 were significantly decreased by heat exposure. The
      results of this study provide new insights into the mechanisms by which heat
      stress affects nutrient absorption in broiler chickens. Our findings suggest that
      periodic heat exposure might alter the jejunal glucose and lipid transport rather
      than amino acid transport. However, intestinal epithelial damage and cell loss
      should be considered when interpreting the effects of heat stress on the
      expression of intestinal transporters.

PMID- 24736813
TI  - Proposals for a new animal health and welfare framework in Wales.

PMID- 24736815
TI  - Maintaining local practices vital to TB control, says BVA President.

PMID- 24736817
TI  - Breaking the itch cycle.

PMID- 24736818
TI  - 3D printing brings a new dimension to implant manufacture.

PMID- 24736819
TI  - Keeping track of illegal medicines residues in food animals.
AB  - In the first article in an occasional series for Veterinary Record, Dorothy Craig
      introduces the work of the Veterinary Residues Committee, the independent
      scientific advisory committee that advises government on the testing of foods
      from animals to look for residues of veterinary medicines and banned substances. 

PMID- 24736820
TI  - Charities join forces to support communities and equids in Haiti.

PMID- 24736821
TI  - Range of ocular deformities in calves due to hypovitaminosis A.
AB  - Hypovitaminosis A responsible for ocular deformities in suckler calves A review
      of type D clostridial enterotoxaemia in cattle Nitrate/nitrite poisoning in kale
      fed lambs Louping ill in sheep in mid-winter Rhodococcus equi abscessation
      identified at meat inspection of fattening pigs These are among matters discussed
      in the disease surveillance report for December 2013 from SAC Consulting:
      Veterinary Services (SAC C VS). 

PMID- 24736822
TI  - Reducing the side effects of cyclophosphamide chemotherapy in dogs.

PMID- 24736823
TI  - Building trust on bovine TB.
AB  - Opinion on how best to control bovine TB remains divided, particularly with
      regard to badgers. Rosie Woodroffe believes that vets have a constructive role to
      play in the debate and helping farmers locally. 

PMID- 24736824
TI  - Clinical examination protocol for the detection of scrapie.

PMID- 24736825
TI  - Hereditary ataxia in Jack Russell terriers in the UK.

PMID- 24736826
TI  - Hereditary ataxia in Jack Russell terriers in the UK.

PMID- 24736828
TI  - Gamma knife radiosurgery for management of cerebral metastases from esophageal
      carcinoma.
AB  - Esophageal carcinoma rarely results in intracranial metastases but when it does,
      the patient prognosis is grim. Because of its rarity outcomes after stereotactic
      radiosurgery (SRS) are not known. We sought to evaluate the outcomes of SRS in
      the management of esophageal cancer that has spread to the brain. This single
      institution retrospective analysis reviewed our experience with esophageal
      metastasis from 1987 to 2013. Thirty patients (36 SRS procedures) with a median
      age of 59 (37-86 years) underwent Gamma knife((r)) SRS. The esophageal origin was
      adenocarcinoma in 26 patients (87%), squamous cell carcinoma in 3 patients (10%),
      and mixed neuroendocrine carcinoma in 1 patient (3%). Fifteen patients were
      treated for a single metastasis and 15 patients were treated for multiple
      metastases for a total of 87 tumors. The median tumor volume was 5.7 cm(3) (0.5
      44 cm(3)) with a median marginal dose of 17 Gy (12-20 Gy). The median survival
      time from the diagnosis of brain metastasis was 8 months and the median survival
      from SRS was 4.2 months. This corresponded to a 6-month survival of 45% and a 12
      month survival of 19% after SRS. A higher KPS at the time of procedure was
      associated with an increase in survival (p = 0.023). The local tumor control rate
      in this group was 92%. Four patients had repeat SRS for new metastatic deposits.
      One patient developed a new neurological deficit after SRS. SRS proved an
      effective means of providing local control for esophageal metastases to the
      brain. Concomitant systemic disease progression at the time of brain metastasis
      resulted in poor long-term survival.

PMID- 24736829
TI  - Clinical management and outcome of histologically verified adult brainstem
      gliomas in Switzerland: a retrospective analysis of 21 patients.
AB  - Because of low incidence, mixed study populations and paucity of clinical and
      histological data, the management of adult brainstem gliomas (BSGs) remains non
      standardized. We here describe characteristics, treatment and outcome of patients
      with exclusively histologically confirmed adult BSGs. A retrospective chart
      review of adults (age >18 years) was conducted. BSG was defined as a glial tumor
      located in the midbrain, pons or medulla. Characteristics, management and outcome
      were analyzed. Twenty one patients (17 males; median age 41 years) were diagnosed
      between 2004 and 2012 by biopsy (n = 15), partial (n = 4) or complete resection
      (n = 2). Diagnoses were glioblastoma (WHO grade IV, n = 6), anaplastic
      astrocytoma (WHO grade III, n = 7), diffuse astrocytoma (WHO grade II, n = 6) and
      pilocytic astrocytoma (WHO grade I, n = 2). Diffuse gliomas were mainly located
      in the pons and frequently showed MRI contrast enhancement. Endophytic growth was
      common (16 vs. 5). Postoperative therapy in low-grade (WHO grade I/II) and high
      grade gliomas (WHO grade III/IV) consisted of radiotherapy alone (three in each
      group), radiochemotherapy (2 vs. 6), chemotherapy alone (0 vs. 2) or no
      postoperative therapy (3 vs. 1). Median PFS (24.1 vs. 5.8 months; log-rank, p =
      0.009) and mOS (30.5 vs. 11.5 months; log-rank, p = 0.028) was significantly
      better in WHO grade II than in WHO grade III/IV tumors. Second-line therapy
      considerably varied. Histologically verification of adult BSGs is feasible and
      has an impact on postoperative treatment. Low-grade gliomas can simple be
      followed or treated with radiotherapy alone. Radiochemotherapy with temozolomide
      can safely be prescribed for high-grade gliomas without additional CNS
      toxicities.

PMID- 24736830
TI  - Yield and utility of routine postoperative imaging after resection of brain
      metastases.
AB  - Magnetic resonance imaging (MRI) or computerized tomography (CT) is routinely
      performed after resection of brain metastases (BrM), regardless of whether there
      are specific clinical concerns about residual tumor or potential complications.
      Routine imaging studies contribute a significant amount to the cost of medical
      care, and their yield and utility are unknown. An IRB-approved retrospective
      chart review study was performed to analyze all craniotomies for BrM performed at
      our institution from 2005 to 2012. Descriptive statistics were used to quantify
      the yield of postoperative imaging. 218 consecutive patients underwent 226
      craniotomies for BrM. In 21 cases, new or worsened neurologic deficits occurred
      after surgery (9.0%), and 19 of the 21 underwent postoperative imaging. 9 of the
      19 patients (47%) had significant findings on postoperative imaging, and 2
      patients required reoperation. 201 patients had no new neurologic deficits (91%),
      and 23 of these patients had no postoperative imaging. Of the 178 remaining
      patients, 160 underwent postoperative MRI and 18 underwent postoperative CT. 9
      patients (5.1%) had unexpected adverse imaging findings; 6 had small stroke, 1
      had a subdural hemorrhage and 2 had possible or definite venous sinus occlusion.
      None of the imaging findings led to changes in management. 182 patients underwent
      imaging appropriate to detect residual tumor (177 gadolinium enhanced MRI and 5
      contrast enhanced CT). Of these patients, 16 were known to have small residual
      tumors based on intraoperative findings. Of the remaining 166 patients felt to
      have had gross total tumor resection, 9 (5.4%) were found to have a small amount
      of residual tumor on postoperative imaging; no patient had a change in treatment
      plan as a result. Routine postoperative imaging in patients undergoing craniotomy
      for BrM has a very low yield and may not be appropriate in the absence of new
      neurologic deficits, or specific clinical concerns about large amounts of
      residual tumor or intraoperative complications.

PMID- 24736832
TI  - In vivo near-infrared photothermal therapy and computed tomography imaging of
      cancer cells using novel tungsten-based theranostic probe.
AB  - Photothermal therapy, as a physical therapeutic technique to kill cancer, has
      generated a great deal of interest. Photothermal agents hence play a critical
      role in this modern therapy. We report the use of transition metal oxides as
      photothermal agents based on PEGylated WO3-x nanoparticles. The well-prepared
      nanoparticles presented effective results during photothermal therapy both in
      vitro and in vivo by using near-IR laser irradiation (980 nm, 0.5 W cm(-2)). The
      tumor cells were effectively damaged using low power density during a short
      irradiation time without destroying healthy tissues. In vitro results of
      photothermal therapy with PEGylated WO3-x nanoparticles proved to be effective on
      4T1 murine breast cancer cells via a confocal microscopy method and MTT assay. In
      vivo results were further confirmed by hematoxylin and eosin (H & E) histological
      staining. Additionally, PEGylated WO3-x nanoparticles were shown to be effective
      as a CT imaging contrast agent on a tumor-bearing mouse model. Our results
      suggest that this generation of PEGylated WO3-x nanoparticles can potentially be
      used in oncological CT imaging and photothermal therapy. 

PMID- 24736833
TI  - Commentaries on Viewpoint: Airway smooth muscle and airway hyperresponsiveness in
      human asthma: have we chased the wrong horse?

PMID- 24736834
TI  - A one-horse race can have only one winner.

PMID- 24736835
TI  - Inhibition of endothelin A receptor protects brain microvascular endothelial
      cells against hypoxia-induced injury.
AB  - Endothelin-1 (ET-1)-induced cell damage is commonly involved in ischemia/hypoxia
      associated diseases. PD155080 [sodium 2-benzo (1.3)dioxol-5-yl-3-benzyl-4-(4
      metho-xyphenyl)-4-oxobut-2-enoate] is a selective endothelin A receptor (ETAR)
      antagonist that inhibits ET-1-induced cell damage. The aim of this study was to
      investigate the effects of PD155080 on hypoxia-induced rat brain microvascular
      endothelial cell (BMEC) injury. BMECs were isolated from the cerebral cortex of
      Wistar rats and cultured in an anoxia chamber, containing 95% N(2) and 5% CO(2)
      for 12 h. BMEC injury was assessed by determining cellular ultra-microstructural
      changes and cell viability by MTT assay, trypan blue (TB) staining and measuring
      the lactate dehydrogenase (LDH) levels. ET-1 mRNA expression was detected by in
      situ hybridization and reverse transcription PCR (RT-PCR); the ET-1 protein level
      was measured by radioimmunoassay. Following exposure to hypoxic conditions, the
      viability of the BMECs was markedly decreased and the ultrastructure of the BMECs
      was damaged, as demonstrated by chromatin margination, chromatin agglutination,
      plasma edema, the increased number of intracellular liposomes and vacuoles,
      mitochondrial swelling and the expansion of a rough surfaced endoplasmic
      reticulum. The levels of ET-1 and ET-1 mRNA expression in the BMECs were
      increased following exposure to hypoxic conditions. Of note, the administration
      of PD155080 greatly enhanced the viability of the BMECs and ameliorated hypoxia
      induced cellular injury. PD155080 also inhibited hypoxia-induced ET-1 production
      by the BMECs. In conclusion, PD155080 exerts protective effects against hypoxia
      induced BMEC injury.

PMID- 24736836
TI  - Dimerization-based control of cooperativity.
AB  - Cooperativity of ligand-receptor binding influences the input-output behavior of
      a biochemical system and thus is an important determinant of its physiological
      function. Canonically, such cooperativity is understood in terms of ligand
      receptor binding affinity, where an initial binding event changes the affinity
      for subsequent binding events. Here, we demonstrate that dimerization-a simple
      yet pervasive signaling motif across biology-can have significant control over
      cooperativity and even dominate over the canonical mechanism. Through an
      exhaustive parameter sensitivity analysis of a general kinetic model for signal
      mediated dimerization, we show that quantitative modulation of dimerization
      processes can reinforce, eliminate, and even reverse cooperativity imposed by the
      canonical allosteric ligand-receptor binding affinity mechanism. The favored
      accumulation of stoichiometrically asymmetric dimers (those with ligand-receptor
      stoichiometry of 1 : 2) is a major determinant of dimerization-based
      cooperativity control. However, simulations demonstrate that favoring
      accumulation of such stoichiometrically asymmetric dimers can either increase or
      decrease cooperativity, and thus the quantitative relationship between
      stoichiometrically asymmetric dimers and cooperativity is highly dependent on the
      parameter values of the particular system of interest. These results suggest that
      the dimerization motif provides a novel mechanism for both generating and
      quantitatively tuning cooperativity that, due to the ubiquity of dimerization
      motifs in biochemical systems, may play a major role in a host of biological
      functions. Thus, the canonical, allosteric view of cooperativity is incomplete
      without considering dimerization effects, which is of particular importance as
      dimerization is often a necessary feature of the allosteric mechanism.

PMID- 24736837
TI  - The association between skilled nursing facility care quality and 30-day
      readmission rates after hospitalization for heart failure.
AB  - The objective of the study was to assess the association between care quality of
      skilled nursing facilities (SNFs) and 30-day risk-adjusted readmission rate (RAR)
      for patients with acute decompensated heart failure (ADHF). A retrospective
      cohort study was conducted involving 603 discharges from a tertiary care hospital
      to 17 SNFs after hospitalization for ADHF. SNF quality was assessed based on the
      CMS 5-star quality rating and a survey of SNF characteristics and processes of
      care. In all, 20% of cases were readmitted within 30-days; 9.4% were for ADHF.
      The all-cause RARs for higher- and lower-quality SNFs were 18% (95% confidence
      interval [CI]=14%-23%) and 22% (95% CI=17%-26%), respectively, and the ADHF RARs
      were 8.8% (95% CI=6.0%-11.6%) and 10.2% (95% CI=7.0%-12.9%), respectively. There
      were no significant associations between ADHF RARs and individual processes of
      care or structural characteristics. Quality ratings of SNF or processes of care
      did not correlate with RAR.

PMID- 24736838
TI  - Ocular albinism type 1-induced melanoma cell migration is mediated through the
      RAS/RAF/MEK/ERK signaling pathway.
AB  - Malignant melanoma has the highest risk of mortality among all types of skin
      cancer due to its highly metastatic potential. The ocular albinism type 1 (OA1)
      protein is a pigment cell-specific glycoprotein, which shares significant
      structural and functional features with G protein-coupled receptors. However, the
      role of OA1 in melanoma has yet to be elucidated. The present study aimed to
      investigate whether OA1 is involved in melanoma cell migration. OA1 was found to
      stimulate cell migration in a dose-dependent manner in cultured human melanoma
      cells. Furthermore, knockdown of OA1 using small interfering RNA was observed to
      significantly inhibit melanoma cell migration. In addition, the mechanism
      underlying OA1-induced melanoma cell migration was investigated. Stimulation of
      the RAS/RAF/mitogen activated protein kinase kinase (MEK)/extracellular signal
      regulated kinase (ERK) pathway using growth factors enhanced OA1 expression and
      melanoma cell migration, whereas inhibition of this pathway using U0126 was
      observed to markedly decrease OA1 expression and the number of migrated cells.
      These findings indicate that OA1 is involved in melanoma cell migration and that
      OA1-induced melanoma cell migration is mediated through the RAS/RAF/MEK/ERK
      signaling pathway. Therefore, OA1 may serve as a novel therapeutic target for
      melanoma. 

PMID- 24736839
TI  - Catalytic bismetallative multicomponent coupling reactions: scope, applications,
      and mechanisms.
AB  - Catalytic reactions have played an indispensable role in organic chemistry for
      the last several decades. In particular, catalytic multicomponent reactions have
      attracted significant attention due to their efficiency and expediency towards
      complex molecule synthesis. The presence of bismetallic reagents (e.g. B-B, Si
      Si, B-Si, Si-Sn, etc.) in this process renders the products enriched with various
      functional groups and multiple stereocenters. For this reason, catalytic
      bismetallative coupling is considered an effective method to generate the
      functional and stereochemical complexity of simple hydrocarbon substrates. This
      review highlights key developments of transition-metal catalyzed bismetallative
      reactions involving multiple pi components. Specifically, it will highlight the
      scope, synthetic applications, and proposed mechanistic pathways of this process.

PMID- 24736840
TI  - Dystrophic muscle environment induces changes in cell plasticity.
AB  - Fibro-adipogenic progenitors (FAPs) reside in the muscle, where they facilitate
      myofiber regeneration. Under normal conditions, FAPs lack myogenic potential and
      thus do not directly contribute to regenerated myofibers. Surprisingly, Saccone
      and colleagues (pp. 841-857) demonstrated that the dystrophic muscle environment
      causes FAPs to adopt a chromatin state that imparts these cells with myogenic
      potential. In this context, treatment of muscle with deacetylase inhibitors
      activates a BAF60c-myomiR transcriptional network in FAPs, blocking adipogenesis
      and driving muscle differentiation. 

PMID- 24736841
TI  - DNA methylation dynamics during epigenetic reprogramming in the germline and
      preimplantation embryos.
AB  - Methylation of DNA is an essential epigenetic control mechanism in mammals.
      During embryonic development, cells are directed toward their future lineages,
      and DNA methylation poses a fundamental epigenetic barrier that guides and
      restricts differentiation and prevents regression into an undifferentiated state.
      DNA methylation also plays an important role in sex chromosome dosage
      compensation, the repression of retrotransposons that threaten genome integrity,
      the maintenance of genome stability, and the coordinated expression of imprinted
      genes. However, DNA methylation marks must be globally removed to allow for
      sexual reproduction and the adoption of the specialized, hypomethylated epigenome
      of the primordial germ cell and the preimplantation embryo. Recent technological
      advances in genome-wide DNA methylation analysis and the functional description
      of novel enzymatic DNA demethylation pathways have provided significant insights
      into the molecular processes that prepare the mammalian embryo for normal
      development. 

PMID- 24736842
TI  - The diabetes gene Hhex maintains delta-cell differentiation and islet function.
AB  - The homeodomain transcription factor HHEX (hematopoietically expressed homeobox)
      has been repeatedly linked to type 2 diabetes mellitus (T2DM) using genome-wide
      association studies. We report here that within the adult endocrine pancreas,
      Hhex is selectively expressed in the somatostatin-secreting delta cell. Using two
      mouse models with Hhex deficiency in the endocrine pancreas, we show that Hhex is
      required for delta-cell differentiation. Decreased somatostatin levels in Hhex
      deficient islets cause disrupted paracrine inhibition of insulin release from
      beta cells. These findings identify Hhex as the first transcriptional regulator
      specifically required for islet delta cells and suggest compromised paracrine
      control as a contributor to T2DM. 

PMID- 24736843
TI  - Coupling 40S ribosome recruitment to modification of a cap-binding initiation
      factor by eIF3 subunit e.
AB  - 40S ribosomes are loaded onto capped mRNAs via the multisubunit translation
      initiation factors eIF3 and eIF4F. While eIF4E is the eIF4F cap recognition
      component, the eIF4G subunit associates with 40S-bound eIF3. How this intricate
      process is coordinated remains poorly understood. Here, we identify an eIF3
      subunit that regulates eIF4F modification and show that eIF3e is required for
      inducible eIF4E phosphorylation. Significantly, recruitment of the eIF4E kinase
      Mnk1 (MAPK signal-integrating kinase 1) to eIF4F depended on eIF3e, and eIF3e was
      sufficient to promote Mnk1-binding to eIF4G. This establishes a mechanism by
      which 40S ribosome loading imparts a phosphorylation mark on the cap-binding
      eIF4F complex that regulates selective mRNA translation and is synchronized by a
      specific eIF3 subunit. 

PMID- 24736844
TI  - miR-99a/100~125b tricistrons regulate hematopoietic stem and progenitor cell
      homeostasis by shifting the balance between TGFbeta and Wnt signaling.
AB  - Although regulation of stem cell homeostasis by microRNAs (miRNAs) is well
      studied, it is unclear how individual miRNAs genomically encoded within an
      organized polycistron can interact to induce an integrated phenotype. miR
      99a/100, let-7, and miR-125b paralogs are encoded in two tricistrons on human
      chromosomes 11 and 21. They are highly expressed in hematopoietic stem cells
      (HSCs) and acute megakaryoblastic leukemia (AMKL), an aggressive form of leukemia
      with poor prognosis. Here, we show that miR-99a/100~125b tricistrons are
      transcribed as a polycistronic message transactivated by the homeobox
      transcription factor HOXA10. Integrative analysis of global gene expression
      profiling, miRNA target prediction, and pathway architecture revealed that miR
      99a/100, let-7, and miR-125b functionally converge at the combinatorial block of
      the transforming growth factor beta (TGFbeta) pathway by targeting four receptor
      subunits and two SMAD signaling transducers. In addition, down-regulation of
      tumor suppressor genes adenomatous polyposis coli (APC)/APC2 stabilizes active
      beta-catenin and enhances Wnt signaling. By switching the balance between Wnt and
      TGFbeta signaling, the concerted action of these tricistronic miRNAs promoted
      sustained expansion of murine and human HSCs in vitro or in vivo while favoring
      megakaryocytic differentiation. Hence, our study explains the high phylogenetic
      conservation of the miR-99a/100~125b tricistrons controlling stem cell
      homeostasis, the deregulation of which contributes to the development of AMKL.

PMID- 24736845
TI  - Structural basis for the Nanos-mediated recruitment of the CCR4-NOT complex and
      translational repression.
AB  - The RNA-binding proteins of the Nanos family play an essential role in germ cell
      development and survival in a wide range of metazoan species. They function by
      suppressing the expression of target mRNAs through the recruitment of effector
      complexes, which include the CCR4-NOT deadenylase complex. Here, we show that the
      three human Nanos paralogs (Nanos1-3) interact with the CNOT1 C-terminal domain
      and determine the structural basis for the specific molecular recognition. Nanos1
      3 bind CNOT1 through a short CNOT1-interacting motif (NIM) that is conserved in
      all vertebrates and some invertebrate species. The crystal structure of the human
      Nanos1 NIM peptide bound to CNOT1 reveals that the peptide opens a conserved
      hydrophobic pocket on the CNOT1 surface by inserting conserved aromatic residues.
      The substitutions of these aromatic residues in the Nanos1-3 NIMs abolish binding
      to CNOT1 and abrogate the ability of the proteins to repress translation. Our
      findings provide the structural basis for the recruitment of the CCR4-NOT complex
      by vertebrate Nanos, indicate that the NIMs are the major determinants of the
      translational repression mediated by Nanos, and identify the CCR4-NOT complex as
      the main effector complex for Nanos function. 

PMID- 24736846
TI  - Distinct regulatory mechanisms balance DegP proteolysis to maintain cellular
      fitness during heat stress.
AB  - Intracellular proteases combat proteotoxic stress by degrading damaged proteins,
      but their activity must be carefully controlled to maintain cellular fitness. The
      activity of Escherichia coli DegP, a highly conserved periplasmic protease, is
      regulated by substrate-dependent allosteric transformations between inactive and
      active trimer conformations and by the formation of polyhedral cages that confine
      the active sites within a proteolytic chamber. Here, we investigate how these
      distinct control mechanisms contribute to bacterial fitness under heat stress. We
      found that mutations that increase or decrease the equilibrium population of
      active DegP trimers reduce high-temperature fitness, that a mutation that blocks
      cage formation causes a mild fitness decrease, and that combining mutations that
      stabilize active DegP and block cage formation generates a lethal rogue protease.
      This lethality is suppressed by an extragenic mutation that prevents covalent
      attachment of an abundant outer-membrane lipoprotein to peptidoglycan and makes
      this protein an inhibitor of the rogue protease. Lethality is also suppressed by
      intragenic mutations that stabilize inactive DegP trimers. In combination, our
      results suggest that allosteric control of active and inactive conformations is
      the primary mechanism that regulates DegP proteolysis and fitness, with cage
      formation providing an additional layer of cellular protection against excessive
      protease activity. 

PMID- 24736849
TI  - Unexpected alpha-alpha interactions with NaV1.5 genetic variants in Brugada
      syndrome.

PMID- 24736847
TI  - Root growth is modulated by differential hormonal sensitivity in neighboring
      cells.
AB  - Coherent plant growth requires spatial integration of hormonal pathways and cell
      wall remodeling activities. However, the mechanisms governing sensitivity to
      hormones and how cell wall structure integrates with hormonal effects are poorly
      understood. We found that coordination between two types of epidermal root cells,
      hair and nonhair cells, establishes root sensitivity to the plant hormones
      brassinosteroids (BRs). While expression of the BR receptor BRASSINOSTEROID
      INSENSITIVE1 (BRI1) in hair cells promotes cell elongation in all tissues, its
      high relative expression in nonhair cells is inhibitory. Elevated ethylene and
      deposition of crystalline cellulose underlie the inhibitory effect of BRI1. We
      propose that the relative spatial distribution of BRI1, and not its absolute
      level, fine-tunes growth. 

PMID- 24736850
TI  - Tracing the proteomic fingerprint of the diabetic aorta?

PMID- 24736852
TI  - Discovery of an obesity susceptibility gene, KSR2, provides new insight into
      energy homeostasis pathways.

PMID- 24736851
TI  - Identification of functional modules by integration of multiple data sources
      using a Bayesian network classifier.
AB  - BACKGROUND: Prediction of functional modules is indispensable for detecting
      protein deregulation in human complex diseases such as cancer. Bayesian network
      is one of the most commonly used models to integrate heterogeneous data from
      multiple sources such as protein domain, interactome, functional annotation,
      genome-wide gene expression, and the literature. METHODS AND RESULTS: In this
      article, we present a Bayesian network classifier that is customized to (1)
      increase the ability to integrate diverse information from different sources, (2)
      effectively predict protein-protein interactions, (3) infer aberrant networks
      with scale-free and small-world properties, and (4) group molecules into
      functional modules or pathways based on the primary function and biological
      features. Application of this model in discovering protein biomarkers of
      hepatocellular carcinoma leads to the identification of functional modules that
      provide insights into the mechanism of the development and progression of
      hepatocellular carcinoma. These functional modules include cell cycle
      deregulation, increased angiogenesis (eg, vascular endothelial growth factor,
      blood vessel morphogenesis), oxidative metabolic alterations, and aberrant
      activation of signaling pathways involved in cellular proliferation, survival,
      and differentiation. CONCLUSIONS: The discoveries and conclusions derived from
      our customized Bayesian network classifier are consistent with previously
      published results. The proposed approach for determining Bayesian network
      structure facilitates the integration of heterogeneous data from multiple sources
      to elucidate the mechanisms of complex diseases.

PMID- 24736853
TI  - Expression quantitative trait locus analysis identifies novel genes for statin
      myopathy.

PMID- 24736854
TI  - Characterization of impurities in commercial spectinomycin by liquid
      chromatography with electrospray ionization tandem mass spectrometry.
AB  - Analysis of commercial spectinomycin samples with ion-pairing reversed-phase LC
      coupled with electrospray ionization tandem MS (LC/ESI-MS/MS) indicates that
      eight additional compounds are present, including actinamine, (4R)
      dihydrospectinomycin, (4S)-dihydrospectinomycin and dihydroxyspectinomycin, as
      well as four new impurities reported, to our knowledge, for the first time. The
      structures of these compounds were elucidated by comparing their fragmentation
      patterns with known structures, and NMR was employed to characterize and
      distinguish (4R)-dihydrospectinomycin and (4S)-dihydrospectinomycin.
      Identification of dihydrospectinomycin isomers is necessary because (4R)
      dihydrospectinomycin is a minor active pharmaceutical ingredient of
      spectinomycin, whereas (4S)-dihydrospectinomycin is considered to be an impurity
      (impurity C) by the European Pharmacopoeia (Ph. Eur.). 

PMID- 24736855
TI  - Comparison between phage-open-reading frame typing and automated repetitive
      sequence-based PCR for typing MRSA isolates.
AB  - The methods for typing and epidemiological study for especially antibiotic
      resistant bacteria has been issued but there are the debates regarding which
      method is best for this purpose. The purpose of this study is to investigate and
      apply a comparatively new technology, phage-open-reading frame typing (POT) and
      repetitive-sequence-based PCR (rep-PCR) using DiversiLab system and compare for
      the discrimination of major methicillin-resistant Staphylococcus aureus (MRSA)
      lineages in epidemiological surveillance. We analyzed 47 representative MRSA
      stains isolated in Kobe University Hospital between January and December 2009. We
      performed MRSA typing using the POT kit and rep-PCR using the DiversiLab system.
      POT method classified all the MRSA strains into 35 clusters, whereas rep-PCR
      method typed all the MRSA strains in 10 kinds of clusters with a definition of
      95% similarity. The discriminatory power and congruence between the methods were
      compared using the Simpson's index of diversity, adjusted Rand's and Wallace's
      coefficients. Our statistical analyses showed that the POT (POT 1-2-3 and POT 2
      3) revealed a higher discriminatory power in the Simpson's index of diversity
      (SID; 0.969, range 0.939-1.000 and 0.967, range 0.935-0.998, respectively) for
      MRSA isolates than the rep-PCR (0.821 (0.767-0.876)). The adjusted Rand's and
      Wallace's coefficients did not show higher concordance among the methods. In
      conclusion, we demonstrated that the POT can perform accurate and reliable
      epidemiological surveillance studies for analyzing the genetic relatedness of
      MRSA strains. 

PMID- 24736856
TI  - Anthracimycin activity against contemporary methicillin-resistant Staphylococcus
      aureus.
AB  - Anthracimycin is a recently discovered novel marine-derived compound with
      activity against Bacillus anthracis. We tested anthracimycin against an expanded
      panel of Staphylococcus aureus strains in vitro and in vivo. All strains of S.
      aureus tested, including methicillin-susceptible, methicillin-resistant (MRSA)
      and vancomycin-resistant strains of S. aureus, were susceptible to anthracimycin
      at MIC values of ?0.25 mg l(-1). Although its postantibiotic effects were
      minimal, anthracimycin exhibited potent and rapid bactericidal activity, with a
      >4-log kill of USA300 MRSA within 3 h at five times its MIC. At concentrations
      significantly below the MIC, anthracimycin slowed MRSA growth and potentiated the
      bactericidal activity of the human cathelicidin, LL-37. The bactericidal activity
      of anthracimycin was somewhat mitigated in the presence of 20% human serum, and
      the compound was minimally toxic to human cells, with an IC50 (inhibitory
      concentration 50)=70 mg l(-1) against human carcinoma cells. At concentrations
      near the MIC, anthracimycin inhibited S. aureus nucleic acid synthesis as
      determined by optimized macromolecular synthesis methodology, with inhibition of
      DNA and RNA synthesis occurring in the absence of DNA intercalation.
      Anthracimycin at a single dose of 1 or 10 mg kg(-1) was able to protect mice from
      MRSA-induced mortality in a murine peritonitis model of infection. Anthracimycin
      provides an interesting new scaffold for future development of a novel MRSA
      antibiotic. 

PMID- 24736857
TI  - Antimicrobial and antiviral sesquiterpenoids from sponge-associated fungus,
      Aspergillus sydowii ZSDS1-F6.

PMID- 24736858
TI  - Glycomyces phytohabitans sp. nov., a novel endophytic actinomycete isolated from
      the coastal halophyte in Jiangsu, East China.
AB  - A novel endophytic actinomycete, designated strain KLBMP 1483(T), was isolated
      from the stem of the coastal plant Dendranthema indicum (Linn.) Des Moul
      collected from Nantong, in East China. Phylogenetic analysis showed that strain
      KLBMP 1483(T) was affiliated with the genus Glycomyces within the family
      Glycomycetaceae and shared the highest 16S rRNA gene sequence similarities with
      the type strains of Glycomyces arizonensis NRRL B-16153(T) (96.7%) and Glycomyces
      tenuis IFO 15904(T) (96.2%), and lower similarities (94.1-95.1%) to the other
      members of the genus Glycomyces, which distinguished KLBMP 1483(T) from
      representatives of the genus Glycomyces. The whole-cell hydrolysates contained
      meso-diaminopimelic acid, glucose, xylose and galactose. The polar lipids were
      diphosphatidylglycerol, phosphatidylglycerol, phosphatidylinositol,
      phosphatidylinositol mannosides, two unknown aminophospholipids, two
      phosphoglycolipids, two unknown phospholipids and one unknown lipid. MK-10(H4)
      was the predominant menaquinone. The major fatty acids were iso-C15:0, anteiso
      C15:0, iso-C16:0, iso-C16:1 G and anteiso-C17:0. On the basis of the phenotypic
      and genotypic characteristics presented in this study, strain KLBMP 1483(T)
      represents a novel species, for which the name Glycomyces phytohabitans sp. nov.
      is proposed. The type strain is KLBMP 1483(T) (NBRC 109116(T)=DSM 45766(T)). 

PMID- 24736859
TI  - Molecular dynamics in azobenzene liquid crystal polymer films measured by time
      resolved techniques.
AB  - Photo-induced molecular motion in a liquid crystal polymer film including
      azobenzene was studied by the heterodyne transient grating method. The film was
      confined in a liquid crystal cell, where it is a photomobile film under free
      standing conditions. By observation of the refractive index change induced by a
      laser pulse, contraction of the film was observed on the order of several
      hundreds of nanoseconds, and the subsequent reorientation and molecular rotation
      dynamics were observed from a few microseconds to a hundred milliseconds.
      Finally, the cis isomer of azobenzene was thermally returned back to the trans
      isomer in about ten seconds because the film could not be bent in the liquid
      crystal cell. Since the contraction, reorientation and molecular rotation took
      place before the cis to trans back-transformation, these processes correspond to
      the preliminary molecular motion preceding the macroscopic bending of the film. 

PMID- 24736860
TI  - Motor learning with fading and growing haptic guidance.
AB  - Haptic guidance has been shown to have both facilitatory and interfering effects
      on motor learning. Interfering effects have been hypothesized to result from the
      particular dynamic environment, which supports a passive role of the learner, and
      they should be attenuated by fading guidance. Facilitatory effects, in particular
      for dynamic movement characteristics, have been hypothesized to result from the
      high-quality information provided by haptic demonstration. If haptic
      demonstration provides particularly precise information about target movements,
      the motor system's need for such information should more likely increase in the
      course of motor learning, in which case growing guidance should be more
      beneficial for learning. We contrasted fading and growing guidance in the course
      of learning a spatio-temporal motor pattern. To stimulate an active role of the
      learner, practice trials consisted of three phases, a visual demonstration of the
      target movement, a guided reproduction, and a reproduction without haptic
      guidance. Performance was assessed in terms of variable duration errors, relative
      timing errors, variable path-length errors, and shape errors. Motor learning with
      growing and fading guidance turned out to be largely equivalent, so that the
      notion of an increasing optimal precision of haptic demonstrations, which matches
      a demand of increasingly precise information on the target movement, found no
      support. Duration errors declined only with fading, but not with growing
      guidance. Relative timing revealed a benefit of immediately preceding haptic
      demonstration, but learning was not different between the two practice protocols.
      This contrast between absolute and relative timing adds to other evidence
      according to which acquisition of these two aspects of motor timing involves
      different learning mechanisms. Whereas relative timing gained from immediately
      preceding haptic demonstration, but revealed no practice-related improvement in
      the presence of haptic guidance, the opposite pattern of results was found for
      the shape error. This finding is consistent with the claim that haptic
      demonstration is particularly efficient with respect to relative timing, but not
      with respect to spatial movement characteristics. 

PMID- 24736861
TI  - Normal aging affects movement execution but not visual motion working memory and
      decision-making delay during cue-dependent memory-based smooth-pursuit.
AB  - Aging affects virtually all functions including sensory/motor and cognitive
      activities. While retinal image motion is the primary input for smooth-pursuit,
      its efficiency/accuracy depends on cognitive processes. Elderly subjects exhibit
      gain decrease during initial and steady-state pursuit, but reports on latencies
      are conflicting. Using a cue-dependent memory-based smooth-pursuit task, we
      identified important extra-retinal mechanisms for initial pursuit in young adults
      including cue information priming and extra-retinal drive components (Ito et al.
      in Exp Brain Res 229:23-35, 2013). We examined aging effects on parameters for
      smooth-pursuit using the same tasks. Elderly subjects were tested during three
      task conditions as previously described: memory-based pursuit, simple ramp
      pursuit just to follow motion of a single spot, and popping-out of the correct
      spot during memory-based pursuit to enhance retinal image motion. Simple ramp
      pursuit was used as a task that did not require visual motion working memory. To
      clarify aging effects, we then compared the results with the previous young
      subject data. During memory-based pursuit, elderly subjects exhibited normal
      working memory of cue information. Most movement-parameters including pursuit
      latencies differed significantly between memory-based pursuit and simple ramp
      pursuit and also between young and elderly subjects. Popping-out of the correct
      spot motion was ineffective for enhancing initial pursuit in elderly subjects.
      However, the latency difference between memory-based pursuit and simple ramp
      pursuit in individual subjects, which includes decision-making delay in the
      memory task, was similar between the two groups. Our results suggest that smooth
      pursuit latencies depend on task conditions and that, although the extra-retinal
      mechanisms were functional for initial pursuit in elderly subjects, they were
      less effective. 

PMID- 24736862
TI  - Integration of vestibular and emetic gastrointestinal signals that produce nausea
      and vomiting: potential contributions to motion sickness.
AB  - Vomiting and nausea can be elicited by a variety of stimuli, although there is
      considerable evidence that the same brainstem areas mediate these responses
      despite the triggering mechanism. A variety of experimental approaches showed
      that nucleus tractus solitarius, the dorsolateral reticular formation of the
      caudal medulla (lateral tegmental field), and the parabrachial nucleus play key
      roles in integrating signals that trigger nausea and vomiting. These brainstem
      areas presumably coordinate the contractions of the diaphragm and abdominal
      muscles that result in vomiting. However, it is unclear whether these regions
      also mediate the autonomic responses that precede and accompany vomiting,
      including alterations in gastrointestinal activity, sweating, and changes in
      blood flow to the skin. Recent studies showed that delivery of an emetic compound
      to the gastrointestinal system affects the processing of vestibular inputs in the
      lateral tegmental field and parabrachial nucleus, potentially altering
      susceptibility for vestibular-elicited vomiting. Findings from these studies
      suggested that multiple emetic inputs converge on the same brainstem neurons,
      such that delivery of one emetic stimulus affects the processing of another
      emetic signal. Despite the advances in understanding the neurobiology of nausea
      and vomiting, much is left to be learned. Additional neurophysiologic studies,
      particularly those conducted in conscious animals, will be crucial to discern the
      integrative processes in the brain stem that result in emesis. 

PMID- 24736863
TI  - Adult cyclical vomiting syndrome: a disorder of allostatic regulation?
AB  - Cyclic vomiting syndrome (CVS) is an idiopathic illness characterized by
      stereotypic and sudden-onset episodes of intense retching and repetitive vomiting
      that are often accompanied by severe abdominal pain. Many associated factors that
      predict CVS attacks, such as prolonged periods of fasting, sleep deprivation,
      physical and emotional stress, or acute anxiety, implicate sympathetic nervous
      system activation as a mechanism that may contribute to CVS pathogenesis.
      Furthermore, adult patients with CVS tend to have a history of early adverse life
      events, mood disorders, chronic stress, and drug abuse-all associations that may
      potentiate sympathetic neural activity. In this review, we set forth a conceptual
      model in which CVS is viewed as a brain disorder involving maladaptive plasticity
      within central neural circuits important for allostatic regulation of the
      sympathetic nervous system. This model not only can account for the varied
      clinical observations that are linked with CVS, but also has implications for
      potential therapeutic interventions. Thus, it is likely that cognitive behavioral
      therapy, stress management ("mind-body") interventions, regular exercise,
      improved sleep, and avoidance of cannabis and opiate use could have positive
      influences on the clinical course for patients with CVS. 

PMID- 24736864
TI  - Autopage and the use of computer scripts to automate microtasks.
AB  - Paging referring clinicians with imaging results is a frequently repeated
      "microtask" performed by practicing radiologists. Many institutions use online
      alpha-paging systems to provide this integral part of safe and efficient patient
      care. Although sending an alpha-page can often be accomplished within one minute,
      current tools may disrupt workflow by distracting users with a series of tedious
      mouse clicks. We describe the development, evaluation, and updates of a portable
      tool that sends alpha-pages to referring clinicians using two keystrokes. This
      software integrates study information obtained from the Picture Archiving and
      Communication System (PACS) with an existing hospital paging system. 

PMID- 24736867
TI  - Teacher stories of blame when assigning a failing grade.
AB  - Nurse educators are required to routinely evaluate students. While there is a
      plethora of information in the educational literature about how to write exams,
      develop rubrics, or evaluate clinical performance, there is a paucity of research
      related to teachers' experiences of evaluation. Using a Heideggerian
      hermeneutical approach, this study sought to answer: (1) what are the experiences
      of nurse educators evaluating nursing students? and (2) what do these evaluative
      experiences mean to the nurse educator? Thirty nurse educators from 19
      undergraduate programs were interviewed for this study. Implications for nurse
      educators are discussed.

PMID- 24736866
TI  - Language mapping with verbs and sentences in awake surgery: a review.
AB  - Intraoperative language mapping in awake surgery is typically conducted by asking
      the patient to produce automatic speech and to name objects. These tasks might
      not map language with sufficient accuracy, as some linguistic processes can only
      be triggered by tasks that use verbs and sentences. Verb and sentence processing
      tasks are currently used during surgery, albeit sparsely. Medline, PubMed, and
      Web of Science records were searched to retrieve studies focused on language
      mapping with verbs/sentences in awake surgery. We review the tasks reported in
      the published literature, spell out the language processes assessed by each task,
      list the cortical and subcortical regions whose stimulation inhibited language
      processing, and consider the types of errors elicited by stimulation in each
      region. We argue that using verb tasks allows a more thorough evaluation of
      language functions. We also argue that verb tasks are preferable to object naming
      tasks in the case of frontal lesions, as lesion and neuroimaging data demonstrate
      that these regions play a critical role in verb and sentence processing. We
      discuss the clinical value of these tasks and the current limitations of the
      procedure, and provide some guidelines for their development. Future research
      should aim toward a differentiated approach to language mapping - one that
      includes the administration of standardized and customizable tests and the use of
      longitudinal neurocognitive follow-up studies. Further work will allow
      researchers and clinicians to understand brain and language correlates and to
      improve the current surgical practice. 

PMID- 24736868
TI  - Porous CuCo2O4 nanocubes wrapped by reduced graphene oxide as high-performance
      lithium-ion battery anodes.
AB  - A composite of porous CuCo2O4 nanocubes well wrapped by reduced graphene oxide
      (rGO) sheets has been synthesized by a facile microwave-assisted solvothermal
      reaction and applied as anode in lithium ion batteries (LIBs). The porous
      structure of the CuCo2O4 nanocubes not only provides a high surface area for
      contact with the electrolyte, but also assists by accommodating volume change
      upon charging-discharging. Impedance measurements and transmission electron
      microscopy show that incorporation of rGO further decreases the charge transfer
      resistance and improves the structural stability of the composite. As an anode
      material for a LIB, the composite exhibits a high stable capacity of ~ 570 mA h
      g(-1) at a current density of 1000 mA g(-1) after 350 cycles. With a high
      specific surface area and a low charge transfer resistance, the composite anode
      shows impressive performance especially at high current density. The LIB shows a
      high capacity of ~ 450 mA h g(-1) even at a high current density of 5000 mA g(
      1), demonstrating the composite's potential for applications in LIBs with long
      cycling life and high power density.

PMID- 24736870
TI  - Anti-inflammatory triterpenoids from the stems of Microtropis fokienensis.
AB  - Three new ursane- and four new oleanane- type triterpenoids 1-7 were isolated,
      along with six known compounds 8-13, from the methanolic extract of Microtropis
      fokienensis. All structures were elucidated by mass and NMR spectroscopic
      methods. The isolates 4-10 and known compounds 14-17 that were previously
      isolated from this material were evaluated for anti-inflammatory activity based
      on effects against superoxide anion generation and elastase release by
      neutrophils in response to fMLP/CB. 11alpha,30-Dihydroxy-2,3-seco-olean-12-en-2,3
      dioic anhydride (7) was the first triterpene anhydride from the genus of
      Microtropis to have the ring A expanded to a seven-membered ring; it showed
      significant anti-inflammatory activity against superoxide anion generation and
      elastase release. Unexpectedly, 30-hydroxy-2,3-seco-lup-20(29)-ene-2,3-dioic acid
      (17) showed the best effect against superoxide anion generation and elastase
      release with IC50 values of 0.06+/-0.01 and 1.03+/-0.35 ug/mL, respectively.
      Compound 17 had a dioic acid function, and compound 7 had an anhydride function
      modification in ring A; both showed promising activity in the target assays.

PMID- 24736871
TI  - A simple model for understanding the fluorescence behavior of Au25 nanoclusters.
AB  - In this work, we synthesized Au25 nanoclusters protected by 2-(naphthalen-2
      yl)ethanethiolate. Our experiments revealed that the luminescence of this
      nanocluster consists of two bands, namely, band I centered at 740 nm and band II
      centered at 680 nm. Compared with 2-phenylethanethiolate protected Au25
      nanoclusters, this new nanocluster has a much higher QY (quantum yield) value
      (6.5 times higher). Fluorescence lifetime measurements showed multiple
      components, i.e. 0.15 ns, ~20 ns and ~150 ns. With an increase in the
      electropositivity of the nanocluster, the fluorescence intensity of the
      nanocluster exhibits a significant enhancement. Since the 2-(naphthalen-2
      yl)ethanethiolate protected Au25 nanocluster shares the same Au13/Au12 core-shell
      structure as the 2-phenylethanethiolate protected nanocluster, the band II
      fluorescence implies that the surface ligands play a major role in the origin of
      the fluorescence. 

PMID- 24736872
TI  - [Sequential digital dermatoscopic imaging. How much time is required per
      patient?].
AB  - BACKGROUND: Melanoma screening is possible using the naked eye, a loupe, a
      dermatoscope or a sequential digital dermatoscopic imaging (SDDI) device. The
      latter provides photodocumentation and makes it possible to assess changes over
      time. One potential disadvantage of this method has been felt to be in the time
      expenditure per patient. OBJECTIVES: Objective was to prospectively assess the
      time required for routine melanoma screening, using a SDDI device. MATERIALS AND
      METHODS: All patients screened for melanoma using a SDDI system (Mole Max2) in a
      private dermatology practice during 1 year were included prospectively. The time
      needed per patient was measured. Suspicious lesions were excised and
      histologically evaluated. The number needed to treat (NNT) was calculated.
      Excisions performed exclusively due to cosmetic reasons were not included.
      RESULTS: 381 patients with 10,356 melanocytic lesions were documented using SDDI
      and clinically assessed (mean: 27.18 melanocytic lesions per patient; min:1,
      max:110). Mean time consumption per lesion was 15.4 s. (min:3, max:57) and per
      patient about 7 min. 98 suspicious lesions were excised, among them13 melanomas;
      yielding a NNT of 7.54. CONCLUSIONS: SDDI can be easily integrated into the daily
      routine; a variety of systems are available. The time required is reasonable,
      about 7 min per patient and about 15 s per lesion. The quality of the evaluation
      is operator-dependent; it can be evaluated by determining the NNT. A major
      advantage of this diagnostic procedure is the photodocumentation which makes it
      possible to assess potential progression of a melanocytic lesion.

PMID- 24736873
TI  - [Post-vaccination granulomas caused by delayed-type reaction to aluminum salts].
AB  - BACKGROUND: Aluminium salts are common adjuvants in all established inactivated
      vaccines. They are necessary to activate the humoral immune system. In the 1990s
      a Swedish study on an acellular vaccination against pertussis was started. Until
      2013, 745 of 760,000 children with pruritic subcutaneous nodules were identified.
      In 77 % of these children a contact allergy to aluminium could be proven. Contact
      allergy to aluminium induced by vaccines causes pruritic subcutaneous nodules at
      the vaccination site. During infections of the upper respiratory tract the
      pruritus often escalates with inflammatory, erythematous and urticarial plaques.
      CONCLUSIONS: The use of solutions containing aluminium salts for specific
      immunotherapy is contraindicated in the case of contact allergy to aluminium.
      Intramuscular injections of inactivated vaccines can be employed to avoid
      granuloma formation.

PMID- 24736874
TI  - Flattening of a patterned compliant solid by surface stress.
AB  - We measured the shape change of periodic ridge surface profiles in gelatin
      organogels resulting from deformation driven by their solid-vapor surface stress.
      A gelatin organogel was molded onto poly-dimethylsiloxane (PDMS) masters having
      ridge heights of 1.7 and 2.7 MUm and several periodicities. Gel replicas were
      found to have a shape deformed significantly compared to their PDMS master.
      Systematically larger deformations in gels were measured for lower elastic
      moduli. Measuring the elastic modulus independently, we estimate a surface stress
      of 107 +/- 7 mN m(-1) for the organogels in solvent composed of 70 wt% glycerol
      and 30 wt% water. Shape changes are in agreement with a small strain linear
      elastic theory. We also measured the deformation of deeper ridges (with height 13
      MUm), and analysed the resulting large surface strains using finite element
      analysis. 

PMID- 24736875
TI  - NTP Monograph: Developmental Effects and Pregnancy Outcomes Associated With
      Cancer Chemotherapy Use During Pregnancy.
AB  - The National Toxicology Program (NTP) Office of Health Assessment and Translation
      (OHAT) conducted an evaluation of the developmental effects and pregnancy
      outcomes associated with cancer chemotherapy use during pregnancy in humans. The
      final NTP monograph was completed in May 2013 (available at http://
      ntp.niehs.nih.gov/go/36495). The incidence of cancer during pregnancy has been
      reported to occur from 17 to 100 per 100,000 pregnant women. Chemotherapy is a
      common treatment for cancer; however, most chemotherapy agents are classified as
      known or suspected human teratogens. Cancer chemotherapy use during pregnancy was
      selected for evaluation by the NTP because of the: (1) paucity of comprehensive
      reviews on the pregnancy outcomes following cancer chemotherapy use during
      pregnancy in humans, including the integration of the developmental animal
      toxicology literature with the observational studies in humans, and (2) growing
      public interest in the developmental effects of chemotherapy on offspring exposed
      to cancer chemotherapy during gestation due to the expected incidence of cancer
      diagnosed during pregnancy as women delay pregnancy to later ages. Of the
      approximately 110 cancer chemotherapeutic agents currently in use, the NTP
      monograph includes data on 56 agents used during 1,261 pregnancies for which
      pregnancy outcomes were documented. Overall, the NTP evaluation found that
      treatment with chemotherapy for cancer appeared to be associated with: (1) a
      higher rate of major malformations following exposure during the first trimester
      compared to exposure in the second and/or third trimester; (2) an increase the
      rate of stillbirth following exposure in the second and/ or third trimester;
      abnormally low levels of amniotic fluid (primarily attributable to Trastuzumab);
      and (3), also data are insufficient, impaired fetal growth and myelosuppression.
      Treatment with chemotherapy for cancer during pregnancy did not appear to
      increase spontaneous preterm birth, or impair normal growth and development of
      offspring during early life. In addition, the NTP monograph provides background
      materials on individual cancer chemotherapeutic agents (e.g., evidence for
      placenta and breast milk transport, developmental toxicity in animals), and a
      brief review of the prevalence and prognosis of seven frequently diagnosed
      cancers in women during pregnancy. Finally, the NTP monograph identifies
      challenges in interpreting the health outcomes from this observational literature
      base and discussed possible actions to improve the understanding of the
      developmental effects of chemotherapy treatment for cancer administered during
      pregnancy. 

PMID- 24736876
TI  - Psychosocial factors predicting survival after allogeneic stem cell transplant.
AB  - PURPOSE: A primary aim was to assess the relative contribution of psychological
      factors, such as anxiety, depression and mental adjustment to cancer, to overall
      survival outcomes at a median follow-up of 2 years following allogeneic
      haematopoietic stem cell transplant (HSCT). A secondary aim was to ascertain if
      demographic, medical and psychosocial factors assessed prior to transplantation
      were predictors of survival for patients after accounting for post-transplant
      events. METHOD: Between 2005 and 2011, 130 allograft patients completed the
      Mental Adjustment to Cancer Scale and Brief Symptom Inventory-18 as part of
      routine psychological assessment before undergoing transplantation. Survival
      status data were obtained, and predictors of survival status assessed and
      analysed using Cox-regression models. RESULTS: Thirteen percent experienced
      clinical levels of distress pre-transplant. None of the psychological factors
      predicted post-HSCT survival. In contrast, hierarchical multivariate analysis
      indicated that post-transplant factors (acute graft-versus-host disease and
      relapse post-transplant) predicted survival (Chi-square change, p < 0.001). The
      addition of a series of pre-transplant psychosocial and medical variables further
      improved the prediction of survival (Chi-square change, p = 0.01). In particular,
      relationship status (being single) (p = 0.04) and increased somatic symptoms (p =
      0.02) pre-transplant were associated with shorter survival. Both variables were
      not associated with medical factors but were related to increased severity of
      anxiety and depressive symptoms as well as greater use of helpless-hopelessness
      and reduced fighting spirit adjustment response. CONCLUSIONS: Despite the
      significant influence of acute post-transplant factors in predicting survival
      following allogeneic HSCT, multidisciplinary pre-transplant assessments are
      important in identifying patients who are likely to experience poorer survival
      outcomes.

PMID- 24736877
TI  - The green tea extract epigallocatechin-3-gallate inhibits irradiation-induced
      pulmonary fibrosis in adult rats.
AB  - The present study evaluated the effect of epigallocatechin-3-gallate (EGCG), the
      most abundant catechin in green tea, on irradiation-induced pulmonary fibrosis
      and elucidated its mechanism of action. A rat model of irradiation-induced
      pulmonary fibrosis was generated using a (60)Co irradiator and a dose of 22 Gy.
      Rats were intraperitoneally injected with EGCG (25 mg/kg) or dexamethasone (DEX;
      5 mg/kg) daily for 30 days. Mortality rates and lung index values were
      calculated. The severity of fibrosis was evaluated by assaying the hydroxyproline
      (Hyp) contents of pulmonary and lung tissue sections post-irradiation. Alveolitis
      and fibrosis scores were obtained from semi-quantitative analyses of hematoxylin
      and eosin (H&E) and Masson's trichrome lung section staining, respectively. The
      serum levels of transforming growth factor beta1 (TGF-beta1), interleukin (IL)-6,
      IL-10, and tumor necrosis factor-alpha (TNF-alpha) were also measured. Surfactant
      protein-B (SPB) and alpha-SMA expression patterns were evaluated using
      immunohistochemistry, and the protein levels of nuclear transcription factor NF
      E2-related factor 2 (Nrf-2) and its associated antioxidant enzymes heme oxygenase
      1 enzyme (HO-1) and NAD(P)H: quinone oxidoreductase-1 (NQO-1) were examined via
      western blot analysis. Treatment with EGCG, but not DEX, reduced mortality rates
      and lung index scores, improved histological changes in the lung, reduced
      collagen depositions, reduced MDA content, enhanced SOD activity, inhibited
      (myo)fibroblast proliferation, protected alveolar epithelial type II (AE2) cells,
      and regulated serum levels of TGF-beta1, IL-6, IL-10, and TNF-alpha. Treatment
      with EGCG, but not DEX, activated Nrf-2 and its downstream antioxidant enzymes HO
      1 and NQO-1. Taken together, these results showed that EGCG treatment
      significantly inhibits irradiation-induced pulmonary fibrosis. Furthermore, the
      results suggested promising clinical EGCG therapies to treat this disorder.

PMID- 24736878
TI  - Heparin monotherapy or bivalirudin during percutaneous coronary intervention in
      patients with non-ST-segment-elevation acute coronary syndromes or stable
      ischemic heart disease: results from the Evaluation of Drug-Eluting Stents and
      Ischemic Events registry.
AB  - BACKGROUND: The use of bivalirudin versus unfractionated heparin monotherapy in
      patients without ST-segment-elevation myocardial infarction is not well defined.
      METHODS AND RESULTS: The study population consisted of patients enrolled in the
      Evaluation of Drug-Eluting Stents and Ischemic Events (EVENT) registry with
      either non-ST-segment-elevation acute coronary syndromes or stable ischemic heart
      disease, who underwent percutaneous coronary intervention with either
      unfractionated heparin or bivalirudin monotherapy. Propensity score matching was
      used to adjust for baseline characteristics. The primary bleeding (in-hospital
      composite bleeding-access site bleeding, thrombolysis in myocardial infarction
      major/minor bleeding, or transfusion) and primary (in-hospital death/myocardial
      infarction) and secondary ischemic outcomes (death/myocardial
      infarction/unplanned repeat revascularization at 12 months) were evaluated.
      Propensity score matching yielded 1036 patients with non-ST-segment-elevation
      acute coronary syndromes and 2062 patients with stable ischemic heart disease.
      For the non-ST-segment-elevation acute coronary syndrome cohort, bivalirudin use
      was associated with lower bleeding (difference, -3.3% [-0.8% to -5.8%]; P=0.01;
      number need to treat=30) without increase in either primary (difference, 1.2%
      [4.1% to -1.8%]; P=0.45) or secondary ischemic outcomes, including stent
      thrombosis (difference, 0.0% [1.3% to -1.3%]; P=1.00). Similarly, in the stable
      ischemic heart disease cohort, bivalirudin use was associated with lower bleeding
      (difference, -1.8% [-0.4% to -3.3%]; P=0.01; number need to treat=53) without
      increase in either primary (difference, 0.4% [2.3% to -1.5%]; P=0.70) or
      secondary ischemic outcomes, including stent thrombosis (difference, 0.0% [0.7%
      to -0.7%]; P=1.00) when compared with unfractionated heparin monotherapy.
      CONCLUSIONS: Among patients with non-ST-segment-elevation acute coronary
      syndromes or stable ischemic heart disease undergoing percutaneous coronary
      intervention, bivalirudin use during percutaneous coronary intervention when
      compared with unfractionated heparin monotherapy was associated with lower
      bleeding without significant increase in ischemic outcomes or stent thrombosis.

PMID- 24736879
TI  - In vivo and in vitro immunomodulatory potential of swertiamarin isolated from
      Enicostema axillare (Lam.) A. Raynal that acts as an anti-inflammatory agent.
AB  - Swertiamarin is a secoiridoid glycoside found in Enicostema axillare (Lam) A.
      Raynal, a medicinal plant used as a depurative in the Indian system of
      traditional medicine. The present study evaluated the immunomodulatory activity
      of isolated swertiamarin. In vivo immunomodulatory activity of swertiamarin (2,
      5, and 10 mg/kg b.w.) was evaluated in a model of sheep red blood cells (SRBC) by
      assessing its effect on organ weight, hemagglutinating antibody titer (HA),
      plaque-forming cells (PFC), quantitative hemolysis of SRBC, and delayed type
      hypersensitivity (DTH). In vitro immunomodulatory potential was studied on
      isolated splenocytes, neutrophils, and peritoneal macrophages. In silico
      immunomodulatory effects were evaluated by docking of swertiamarin on
      proinflammatory cytokines to confirm its potential. In in vivo studies, the
      animals treated with swertiamarin showed a significant (P <= 0.05) increase in
      antibody titer, plaque-forming cells, and also in weight of the thymus and
      spleen. A decreased response to DTH reaction was recorded with the treatment of
      swertiamarin. In in vitro studies, treatment with swertiamarin modulated the
      messenger RNA (mRNA) and protein expression of IFN-gamma, IL-10, and IL-4
      significantly (P <= 0.05) and also favored Th2-mediated response on concanavalin
      A (Con A)-induced splenocytes. The compound inhibited the release of free
      radicals significantly (P <= 0.05) in phytohemagglutinin (PHA)-induced
      neutrophils and also ameliorated the mRNA and protein expression of
      proinflammatory cytokines (TNF-alpha, IL-1beta, and IL-6) in lipopolysaccharide
      (LPS)-induced macrophages. In in silico, the best docked pose of swertiamarin
      with the target proteins (TNF-alpha, IL-1beta, and IL-6) was confirmed that
      swertiamarin acted as an anti-inflammatory mediator.

PMID- 24736880
TI  - Protective effects of Lactobacillus plantarum NDC 75017 against
      lipopolysaccharide-induced liver injury in mice.
AB  - This study investigated the protective effect of Lactobacillus plantarum NDC
      75017 (L. plantarum NDC 75017) against acute liver injury induced by
      lipopolysaccharide (LPS). Thirty male mice were randomly divided into the
      control, LPS, and LPS + L. plantarum NDC 75017 groups. In the LPS + L. plantarum
      group, the mice were orally pretreated with L. plantarum NDC 75017 for 15 days.
      At 16 days, the mice in the LPS and LPS + L. plantarum NDC 75017 groups were
      intraperitoneally injected with LPS at 4 mg/kg body weight, whereas the control
      mice were treated with an equal amount of saline. After 8 h, the serum alanine
      transaminase (ALT), aspartate aminotransferase (AST), and histology changes were
      examined. The oxidative stress markers and pro-inflammatory cytokines in the
      liver were also examined. Meanwhile, the expression of nuclear factor kappaB (NF
      kappaB) mRNA and toll-like receptor 4 (TLR4) in the liver was determined by qRT
      PCR. The LPS group showed an increase in ALT and AST, whereas the LPS + L.
      plantarum NDC 75017 group showed a significant decrease. In addition,
      pretreatment with L. plantarum NDC 75017 can attenuate LPS-induced oxidative
      stress and inflammatory response. Furthermore, the increase of hepatic NF-kappaB
      and TLR4 mRNA induced by LPS was significantly downregulated by the pretreatment
      with L. plantarum NDC 75017. These data show that pretreatment with L. plantarum
      NDC 75017 protects against LPS-induced oxidative stress and inflammatory injury
      in the liver of mice, which may be attributed to the inhibition of the TLR4-NF
      kappaB pathway. 

PMID- 24736881
TI  - Ginsenoside metabolite compound k alleviates adjuvant-induced arthritis by
      suppressing T cell activation.
AB  - Ginsenoside metabolite compound K (CK) is the degradation product of ginsenosides
      in the intestine by bacteria and has many pharmacological activities including
      anti-inflammatory effects. Rheumatoid arthritis (RA) is an inflammatory and
      autoimmune disease characterized by chronic synovial inflammation and articular
      damage in multiple joints. However, the effect of CK on RA remains unclear. In
      this study, the effect of CK on adjuvant arthritis (AA) and the underlying
      mechanisms that focused on T cell activation were investigated. Complete Freund's
      adjuvant was used to induce AA rats. After the onset of arthritis, rats were
      given CK (10, 40, and 160 mg/kg) or MTX (0.5 mg/kg). To evaluate the severity of
      arthritis, arthritis index and paw swelling were evaluated every 3 days.
      Histopathology of joint and spleen were assayed. Subsets of T cells including
      CD4+CD62L+ (naive T cells), CD4+CD25+ (activated T cells), and CD4+CD25 + Foxp3+
      cells (Treg) and CD25 expression were assayed by flow cytometry. Proliferation of
      T cell was evaluated by (3)H-TdR. IL-2 level was assayed by ELISA. We found that
      CK attenuated arthritis index and paw swelling, restored the histopathological
      change of joint and spleen, downregulated the percentage of activated T cells,
      and upregulated naive T cells and Treg cells in spleen. CK significantly
      suppressed T cell activation (as indicated by T cell proliferation, CD25
      expression, and IL-2 production). In conclusion, our results suggest that CK
      alleviates autoimmune arthritis by suppressing T cell activation.

PMID- 24736882
TI  - Serum-soluble HLA-G is associated with specific IgE in patients with allergic
      rhinitis and asthma.
AB  - Allergic rhinitis (AR) and allergic asthma (AA) are characterized by T helper
      (Th)2-polarized immune response. Soluble human leukocyte antigen G (sHLA-G)
      molecule plays an immunomodulatory activity. Previously, it has been reported
      that children with AR or AA had higher sHLA-G levels in comparison with normal
      subjects. Thus, the present study aimed at confirming these data in adults and
      investigating whether there was a relationship between serum sHLA-G levels and
      serum IgE levels, in patients with AR or AA. One hundred twenty symptomatic
      patients, suffering from respiratory symptoms, were enrolled: 45 non-allergic and
      75 allergic. A group of 44 healthy subjects was considered as control. Serum sHLA
      G levels and serum allergen-specific IgE were determined by immunoenzymatic
      methods. Allergic patients had significantly higher levels of sHLA-G molecules
      than non-allergic patients and normal controls (p<0.0001). There was no
      difference between AR and AA. sHLA-G moderately related with allergen-specific
      IgE both in AR (r=0.468) and AA patients (r=0.479). The present study confirms
      that serum sHLA-G molecules are significantly increased in allergic disease and
      demonstrates that sHLA-G levels are related with allergen-specific IgE levels.

PMID- 24736884
TI  - Rates of non-vertebral osteoporotic fractures in rheumatoid arthritis and
      postfracture osteoporosis care in a period of evolving clinical practice
      guidelines.
AB  - In 2002, guidelines for the management of osteoporosis were published by
      Osteoporosis Canada and widely disseminated. We aimed to assess if those
      guidelines had any impact on clinical practice and ultimately on fracture rates
      in rheumatoid arthritis (RA). This was an observational study using the Quebec
      healthcare databases. To quantify the use of osteoporosis drugs, hormone
      replacement therapy (HRT), bone mineral density (BMD) testing, and fracture
      rates, quarterly age-standardized rates between 1998 and 2008 were calculated. A
      time series approach was used to predict fracture rates from 2003 onward, based
      on the earlier data. The provision of postfracture osteoporosis care, as defined
      by the initiation of osteoporosis drugs, HRT, or BMD testing, was examined; and
      logistic regressions identified factors associated with care. The study
      population in each quarter was mainly composed of older women. The use of
      osteoporosis drugs and BMD testing increased over the study period. The actual
      fracture rates from 2003 onward fell within the projected rates and their 95 % CI
      indicating no reduction. A total of 1,279 subjects were included in the
      postfracture care analysis. Over time, the likelihood of receiving osteoporosis
      care increased by 64 % (OR = 1.64, 95 % CI 1.27-2.11), and the two strongest
      predictors of care were female gender and corticosteroid use. Over our study
      period, fracture rates remained stable in this RA population. However, the use of
      osteoporosis drugs, BMD testing, and provision of postfracture osteoporosis care
      improved, which may result from gradual adoption of guidelines.

PMID- 24736883
TI  - Serum ficolin-2 in hospitalised patients with community-acquired pneumonia.
AB  - Mannose binding lectin (MBL) and ficolins contribute to host defence through
      activation of the lectin pathway of complement. In this study, serum levels of
      ficolin-2 and MBL were determined in 276 patients with community-acquired
      pneumonia (CAP). MBL deficiency and ficolin-2 insufficiency were defined using
      previously validated cut-offs. No differences were observed in MBL or ficolin-2
      between patients and controls. MBL-deficient patients (<500 ng/ml) were not at
      higher risk of 30-day mortality odds ratio (OR) 0.97 (0.38-2.48,p=0.9) or a
      composite outcome of mortality, mechanical ventilation, vasopressor support
      (MV/VS) or complications OR 0.89 (0.44-1.77, p=0.9). Although no significant
      relationship between ficolin-2 insufficiency and outcome was observed, very low
      ficolin-2 levels (<1,200 ng/ml) were associated with an OR 1.23 (0.15-10.1),
      p=0.6 for 30-day mortality, 3.05 (0.61-15.2, p=0.2) for MV/VS and OR 2.05 (0.52
      8.1, p=0.2) for the composite outcome. Low serum levels of MBL and ficolin-2 are
      not associated with CAP susceptibility. The high frequency of ficolin-2
      insufficiency in patients with severe CAP would justify a larger investigation of
      ficolin-2 as a modifier of CAP severity.

PMID- 24736885
TI  - Bone structure and estimated bone strength in obese patients evaluated by high
      resolution peripheral quantitative computed tomography.
AB  - Obesity is associated with high bone mineral density (BMD), but whether obesity
      related higher bone mass increases bone strength and thereby protect against
      fractures is uncertain. We estimated effects of obesity on bone microarchitecture
      and estimated strength in 36 patients (12 males and 24 females, age 25-56 years
      and BMI 33.2-57.6 kg/m(2)) matched with healthy controls (age 25-54 years and BMI
      19.5-24.8 kg/m(2)) in regard to gender, menopausal status, age (+/-6 years) and
      height (+/-6 cm) using high resolution peripheral quantitative computed
      tomography and dual energy X-ray absorptiometry. In radius, total bone area and
      trabecular area were significantly higher in obese patients (both p < 0.04). In
      tibia, cortical area was larger in obese patients (p < 0.001) compared with
      controls. Total BMD was higher in tibia (p = 0.03) but not in radius. Trabecular
      integrity was strengthened in obese patients compared with controls in radius and
      tibia with higher trabecular number (p = 0.002 and p < 0.001) and lower
      trabecular spacing (p = 0.01 and p < 0.001). Finite element analysis estimated
      failure load (FL) was higher in tibia (p < 0.001), but not in radius in obese
      patients. FL was significantly lower per kg body weight in radius and tibia in
      obese patients compared with controls (p = 0.007 and p < 0.001). Furthermore, the
      ratios of FLs between groups were comparable in both sites. These findings
      suggest that mechanical loading is not the primary mediator of the effects of
      obesity on estimated FL, and suggest that bone strength adaptations in morbid
      obesity may be inadequate with respect to the increased mechanical demands.

PMID- 24736887
TI  - Increased platelet indices in acute stent thrombosis--response letter.

PMID- 24736888
TI  - Wound healing reduces stress-induced immune changes: evidence for immune
      prioritization in the side-blotched lizard.
AB  - Immune system function is affected by a variety of exogenous and endogenous
      stressors. Most studies have focused on the effect of stressors on immune
      function, but not necessarily on trade-offs within the immune system and
      interactions with energy-mobilizing hormones. In this study, we examined how
      bactericidal ability and corticosterone interacted by applying acute restraint
      stress in a non-model organism, the side-blotched lizard (Uta stansburiana), 10
      days after receiving a cutaneous wound. We found a decrease in bactericidal
      ability in wounded animals after restraint stress. However, the percentage healed
      during the first 7 days was positively correlated with bactericidal ability 10
      days after wounding. In addition, the magnitude of change in corticosterone
      concentration during the acute stress was positively correlated with the
      percentage of wound healing during the first 3 days. These two relationships may
      demonstrate a "faster is better" strategy. If energy is invested heavily in the
      initial wound healing stages, the individual may be able to mount a more
      effective immune and stress response earlier.

PMID- 24736889
TI  - A graphical method to compare the in vivo binding potential of PET radioligands
      in the absence of a reference region: application to [11C]PBR28 and [18F]PBR111
      for TSPO imaging.
AB  - Positron emission tomography (PET) radioligands for a reversible central nervous
      system (CNS) demand a high specific to nonspecific signal characterized by the
      binding potential (BPND). The quantification of BPND requires the determination
      of the nondisplaceable binding usually derived from a reference region devoid of
      the target of interest. However, for many CNS targets, there is no valid
      reference region available. In such cases, the total volume of distribution (VT)
      is often used as the outcome measure, which includes both the specific and
      nonspecific binding signals. Here we present a graphical method that allows for
      direct comparison of the binding potential of ligands using the regional VT data
      alone via linear regression. The method was first validated using literature data
      for five serotonin transporter ligands, for which a reference region exists, and
      then applied to two second generation 18 kDa translocator protein radioligands,
      namely [(11)C]PBR28 and [(18)F]PBR111. The analysis determined that [(11)C]PBR28
      had a higher BPND than [(18)F]PBR111.

PMID- 24736890
TI  - Determination of vessel cross-sectional area by thresholding in Radon space.
AB  - The cross-sectional area of a blood vessel determines its resistance, and thus is
      a regulator of local blood flow. However, the cross-sections of penetrating
      vessels in the cortex can be non-circular, and dilation and constriction can
      change the shape of the vessels. We show that observed vessel shape changes can
      introduce large errors in flux calculations when using a single diameter
      measurement. Because of these shape changes, typical diameter measurement
      approaches, such as the full-width at half-maximum (FWHM) that depend on a single
      diameter axis will generate erroneous results, especially when calculating flux.
      Here, we present an automated method--thresholding in Radon space (TiRS)--for
      determining the cross-sectional area of a convex object, such as a penetrating
      vessel observed with two-photon laser scanning microscopy (2PLSM). The
      thresholded image is transformed back to image space and contiguous pixels are
      segmented. The TiRS method is analogous to taking the FWHM across multiple axes
      and is more robust to noise and shape changes than FWHM and thresholding methods.
      We demonstrate the superior precision of the TiRS method with in vivo 2PLSM
      measurements of vessel diameter.

PMID- 24736892
TI  - Lassen's equation is a good approximation of permeability-surface model: new
      alpha values for 99mTc-HMPAO and 99mTc-ECD.
AB  - Brain perfusion tracers like [(99m)Tc] d,l-hexamethyl-propyeneamine oxime
      ((99m)Tc-HMPAO) and [(99m)Tc] ethyl-cysteinate dimer ((99m)Tc-ECD) underestimate
      regional cerebral blood flow (rCBF) at high flow values. To improve linearity
      between tracer accumulation and rCBF, two different models have been proposed.
      One is Lassen's correction algorithm for back-diffusion of tracer, and the other
      is based on the permeability-surface (PS) model for correction of low first-pass
      extraction. Although both these models have the same goal, they have completely
      different forms of equation. It was demonstrated that mathematical approximation
      of the PS model equation leads to Lassen's equation. In this process, the
      relationship between PS, CBF values and Lassen's parameter was acquired, and how
      to correct both the back-diffusion and low first-pass extraction was also
      demonstrated. A computer simulation confirmed that the two models provided
      similar consequences when the parameter value is chosen according to the
      relationship found. Lassen's equation can be used to correct not only back
      diffusion but also low first-pass extraction. To perform overall correction, the
      parameter value we have been using for decades may be too weak. I estimated that
      the parameter value for overall correction of HMPAO would be around 0.5, and that
      of ECD would be around 0.65. 

PMID- 24736891
TI  - beta-Amyloid is associated with aberrant metabolic connectivity in subjects with
      mild cognitive impairment.
AB  - Positron emission tomography (PET) studies using [18F]2-fluoro-2-deoxyglucose
      (FDG) have identified a well-defined pattern of glucose hypometabolism in
      Alzheimer's disease (AD). The assessment of the metabolic relationship among
      brain regions has the potential to provide unique information regarding the
      disease process. Previous studies of metabolic correlation patterns have
      demonstrated alterations in AD subjects relative to age-matched, healthy control
      subjects. The objective of this study was to examine the associations between
      beta-amyloid, apolipoprotein E E4 (APOE E4) genotype, and metabolic correlations
      patterns in subjects diagnosed with mild cognitive impairment (MCI). Mild
      cognitive impairment subjects from the Alzheimer's Disease Neuroimaging
      Initiative (ADNI) study were categorized into beta-amyloid-low and beta-amyloid
      high groups, based on quantitative analysis of [18F]florbetapir PET scans, and
      APOE E4 non-carriers and carriers based on genotyping. We generated voxel-wise
      metabolic correlation strength maps across the entire cerebral cortex for each
      group, and, subsequently, performed a seed-based analysis. We found that the APOE
      E4 genotype was closely related to regional glucose hypometabolism, while
      elevated, fibrillar beta-amyloid burden was associated with specific derangements
      of the metabolic correlation patterns. 

PMID- 24736893
TI  - microRNAs mediate oleic acid-induced acute lung injury in rats using an
      alternative injury mechanism.
AB  - Intravenous (IV) infusion of oleic acid (OA) distributes OA microemboli in the
      pulmonary capillaries, which results in severe vascular congestion, hemorrhage
      vascular congestion, interstitial edema, intravascular coagulation and bleeding.
      The immune response to acute lung injury (ALI) is known to be associated with
      rapid and widespread changes in microRNA (miRNA) expression in the lung. The
      present study of a model of rat lung injury aimed to investigate how the lung
      miRNA profile changes to mediate ALI. For the induction of ALI, OA (200 ul/kg)
      suspended in 20% ethyl alcohol was injected through the tail vein for 20 min.
      Lung tissue samples were acquired at 3, 6 and 24 h, and miRNA microarray and
      quantitative polymerase chain reaction were performed using these samples. The
      activation of phosphatase and tensin homolog (PTEN), protein kinase B (Akt),
      extracellular signal-regulated kinases (ERK) and c-Jun N-terminal kinases (JNK)
      were analyzed by western blot analysis. There were 75 miRNAs that demonstrated
      >1.5-fold changes in expression levels. miR-101a was highly upregulated at 3 h.
      miR-21 was upregulated in the OA group throughout the 24 h following OA
      challenge. miR-1 was the most downregulated miRNA at 24 h. In order to examine
      the expression levels of PTEN and Akt as targets of miR-21, western blot analysis
      was performed. At 3 h, the levels of PTEN were attenuated in the OA group as
      compared with those in the control group; however, p-Akt/Akt levels were
      increased at 3 h for the OA group. PTEN and p-Akt/Akt were significantly higher
      in the OA group at 3 h and were rapidly decreased at 6 h. The immunohistochemical
      stain of alpha-smooth muscle actin in the bronchial and alveolar wall increased
      24 h after OA-induced ALI. These results indicated that the profile of miRNAs
      dynamically changed throughout the OA-induced ALI process, and mitogen-activated
      protein kinase activation, PTEN/Akt pathway alteration and smooth muscle actin
      activation were observed in this ALI model. 

PMID- 24736894
TI  - Characterization of drug-related problems identified by clinical pharmacy staff
      at Danish hospitals.
AB  - BACKGROUND: In 2010, a database of drug related problems (DRPs) was implemented
      to assist clinical pharmacy staff in documenting clinical pharmacy activities
      locally. A study of quality, reliability and generalisability showed that
      national analyses of the data could be conducted. Analyses at the national level
      may help identify and prevent DRPs by performing national interventions.
      OBJECTIVE: The aim of the study was to explore the DRP characteristics as
      documented by clinical pharmacy staff at hospital pharmacies in the Danish DRP
      database during a 3-year period. SETTING: Danish hospital pharmacies. METHOD:
      Data documented in the DRP-database during the initial 3 years after
      implementation were analyzed retrospectively. The DRP-database contains DRPs
      reported at hospitals by clinical pharmacy staff. The analyses focused on DRP
      categories, implementation rates and drugs associated with the DRPs. MAIN OUTCOME
      MEASURE: Characteristics of DRPs. RESULTS: In total, 72,044 DRPs were documented
      in the DRP-database during the first 3 years of implementation, and the number of
      documented DRPs increased every year. An overall stable implementation rate of
      approximately 58 % was identified. The DRPs identified were multi-facetted,
      however evenly distributed for each of the 3 years. The most frequently
      identified DRP categories were: "Dose", followed by "Nonadherence to guidelines"
      and "Supplement to treatment". The highest implementation rates were found for
      the following DRP categories: "Non-adherence to guidelines" (79 %) followed by
      "Therapeutic duplication" (73 %) and "Dosing time and interval" (70 %). Even
      though the top 25 drugs were involved in 58 % of all DRPs, multiple drugs were
      associated with DRPs. The drugs most frequently involved in DRPs were paracetamol
      (4.6 % of all DRPs), simvastatin (3.0 %), lansoprazole (2.7 %), morphine (2.6 %)
      and alendronic acid (2.4 %). CONCLUSIONS: The study found that a national
      database on DRPs contained multi-facetted DRPs, however evenly distributed for
      each of the 3 years. Even though the top 25 drugs were involved in 58 % of all
      DRPs, multiple drugs were associated with DRPs. The study emphasizes the
      importance of detecting and intervening for DRPs.

PMID- 24736895
TI  - Large scale implementation of clinical medication reviews in Dutch community
      pharmacies: drug-related problems and interventions.
AB  - BACKGROUND: Research on the benefits of clinical medication reviews (CMRs)
      performed by pharmacists has been conducted mostly in controlled settings and has
      been widely published. Less is known of the effects after large scale
      implementation in community pharmacies. An online CMR tool enabled the systematic
      registration of drug-related problems (DRPs) and implemented interventions
      derived from CMRs in daily practice. OBJECTIVE: To describe the effects of CMRs
      on pharmacy practice after large-scale implementation in the Netherlands.
      SETTING: 268 community pharmacies. Pharmacists were trained on CMRs with a
      patient centred approach. METHOD: Retrospective analyses of DRPs, pharmacists'
      proposals and implemented interventions recorded between January 1st and
      September 1st 2012. MAIN OUTCOME MEASURE: Frequencies of DRPs, intervention
      proposals, implemented interventions, and drugs involved. RESULTS: 4,579 CMRs
      were analysed. On average 2.9 (SD 2.1) DRPs per review were identified. 4,123 (31
      %) of the DRPs led to medication changes. Stopping a drug (16 %) was more
      frequent than starting a drug (8.1 %). Drugs related to cardiovascular risk
      management, diabetes and osteoporosis were most frequently involved. CONCLUSION:
      This study is the largest analysis of pharmacists-initiated CMRs in the
      Netherlands to date. The findings demonstrate the potential to reduce medication
      related errors through pharmacist involvements in complex pharmacotherapy and the
      positive impact on the quality of drug therapy through making necessary
      medication changes. The data also support the need for large-scale implementation
      of pharmacists-initiated CMRs in the presence of proper training programmes.

PMID- 24736896
TI  - Assessment of satisfaction with pharmaceutical services in patients receiving
      antiretroviral therapy in outpatient HIV treatment setting.
AB  - BACKGROUND: The patient's perception and satisfaction are increasingly considered
      as a useful factor in the assessment of competency of health care providers and
      quality of care. However, these patient focused assessments are largely ignored
      when assessing health care outcomes. OBJECTIVE: The study assessed the perception
      and satisfaction of patients receiving antiretroviral therapy (ART) with
      pharmaceutical services received in outpatient HIV treatment settings. SETTING:
      Seventeen HIV treatment centres in Nigeria. METHODS: This cross-sectional survey
      included 2,700 patients randomly selected from 26,319 HIV patients on ART, who
      received pharmaceutical services in the study setting. A study-specific Likert
      type instrument was administered to the participants at point of exit from the
      pharmacy. Midpoint of the 5-point scale was computed and scores above it were
      regarded as positive while below as negative. Chi-square was used for inferential
      statistics. All reported p values were 2-sided at 95 % confidence interval (CI).
      MAIN OUTCOME MEASURE: Patient satisfaction with pharmaceutical services. RESULTS:
      Of 2,700 patients sampled, data from 1,617 (59.9 %) were valid for analysis; 62.3
      % were aged 26-40 years and 65.4 % were females. The participants had received
      pharmaceutical services for a mean duration of 25.2 (95 % CI 24.3-26.1) months.
      Perception of participants regarding the appearance of pharmacy was positive
      while that regarding the pharmacists' efforts to solve patients' medication
      related problems was negative. The participants' rating of satisfaction with the
      waiting time to access pharmaceutical services was negative; the satisfaction
      decreases with increasing waiting time. However, the satisfaction with the
      overall quality of pharmaceutical services received was rated as positive; 90.0 %
      reported that they got the kind of pharmaceutical services they wanted; 98.2 %
      would come back to the pharmacy if they were to seek help again and would
      recommend services to others. The level of satisfaction was found to be
      associated with educational status of the participants (p = 0.006) unlike age,
      sex, marital and employment status. CONCLUSION: The satisfaction with overall
      quality of pharmaceutical services received by participants was positive. Longer
      waiting times resulted in lower patient satisfaction. High patient load may be
      the cause of the long waiting time and the inadequate duration of interaction
      between pharmacist and the patient.

PMID- 24736897
TI  - Nitrates and glucosinolates as strong determinants of the nutritional quality in
      rocket leafy salads.
AB  - Rocket is an important leafy vegetable crop and a good source of antioxidants and
      anticancer molecules such as glucosinolates and other sulfur compounds. Rocket is
      also a hyper-accumulator of nitrates which have been considered for long time the
      main factors that cause gastro-intestinal cancer. In this review, the content of
      these compounds in rocket tissues and their levels at harvest and during storage
      are discussed. Moreover, the effect of these compounds in preventing or inducing
      human diseases is also highlighted. This review provides an update to all the
      most recent studies carried out on rocket encouraging the consumption of this
      leafy vegetable to reduce the risk of contracting cancer and other cardiovascular
      diseases.

PMID- 24736899
TI  - Facile synthesis of Au-SnO2 hybrid nanospheres with enhanced photoelectrochemical
      biosensing performance.
AB  - Au-SnO2 hybrid nanospheres (HNSs) were synthesized by a facile, one-step method,
      which was achieved via a redox reaction between the reductive stannous (II) ions
      and oxidative auric (III) ions and dissolved O2, and then in situ formation of Au
      nanoparticles (NPs) and SnO2 NPs. The results indicated that the Au NPs are able
      to trap electrons, improve the electron-hole pairs' life, and enhance the visible
      light absorption intensity that are all beneficial for enhancement of the visible
      light photoelectrochemical performance. Cysteine was chosen as a model molecule
      in photoelectrochemical biosensing experiments. The biosensor displayed excellent
      analytical performance for detection of cysteine with an extremely broad linear
      range (from 0.4 MUM to 12 mM), and a low detection limit (0.1 MUM). Therefore,
      the Au-SnO2 HNSs will be promising candidates for photocatalysts,
      photoelectrochemical biosensors, and other photoelectric devices.

PMID- 24736900
TI  - Depletion region effect of highly efficient hole conductor free CH3NH3PbI3
      perovskite solar cells.
AB  - The inorganic-organic perovskite is currently attracting a lot of attention due
      to its use as a light harvester in solar cells. The large absorption
      coefficients, high carrier mobility and good stability of organo-lead halide
      perovskites present good potential for their use as light harvesters in
      mesoscopic heterojunction solar cells. This work concentrated on a unique
      property of the lead halide perovskite, its function simultaneously as a light
      harvester and a hole conductor in the solar cell. A two-step deposition technique
      was used to optimize the perovskite deposition and to enhance the solar cell
      efficiency. It was revealed that the photovoltaic performance of the hole
      conductor free perovskite solar cell is strongly dependent on the depletion layer
      width which was created at the TiO2-CH3NH3PbI3 junction. X-ray diffraction
      measurements indicate that there were no changes in the crystallographic
      structure of the CH3NH3PbI3 perovskite over time, which supports the high
      stability of these hole conductor free perovskite solar cells. Furthermore, the
      power conversion efficiency of the best cells reached 10.85% with a fill factor
      of 68%, a Voc of 0.84 V, and a Jsc of 19 mA cm(-2), the highest efficiency to
      date of a hole conductor free perovskite solar cell. 

PMID- 24736898
TI  - Dietary patterns in children with attention deficit/hyperactivity disorder
      (ADHD).
AB  - The role of diet in the behavior of children has been controversial, but the
      association of several nutritional factors with childhood behavioral disorders
      has been continually suggested. We conducted a case-control study to identify
      dietary patterns associated with attention deficit hyperactivity disorder (ADHD).
      The study included 192 elementary school students aged seven to 12 years. Three
      non-consecutive 24-h recall (HR) interviews were employed to assess dietary
      intake, and 32 predefined food groups were considered in a principal components
      analysis (PCA). PCA identified four major dietary patterns: the "traditional"
      pattern, the "seaweed-egg" pattern, the "traditional-healthy" pattern, and the
      "snack" pattern. The traditional-healthy pattern is characterized by a diet low
      in fat and high in carbohydrates as well as high intakes of fatty acids and
      minerals. The multivariate-adjusted odds ratio (OR) of ADHD for the highest
      tertile of the traditional-healthy pattern in comparison with the lowest tertile
      was 0.31 (95% CI: 0.12-0.79). The score of the snack pattern was positively
      associated with the risk of ADHD, but a significant association was observed only
      in the second tertile. A significant association between ADHD and the dietary
      pattern score was not found for the other two dietary patterns. In conclusion,
      the traditional-healthy dietary pattern was associated with lower odds having
      ADHD.

PMID- 24736901
TI  - Antimicrobial resistance--a ticking bomb!

PMID- 24736902
TI  - Universal neonatal hearing screening: neonatologist's perspective.

PMID- 24736903
TI  - Neonatal hearing screening: otolaryngologist's perspective.

PMID- 24736904
TI  - Difficulties mastered are opportunities won: pulmonologist's perspective.

PMID- 24736905
TI  - CFTR mutations in India: need to do more!: geneticist's perspective.

PMID- 24736906
TI  - Pharmacokinetics of nevirapine, stavudine and lamivudine in Indian HIV-infected
      children receiving generic fixed dose combinations.
AB  - OBJECTIVE: To determine the trough and two hour plasma levels of nevirapine,
      stavudine, and lamivudine when administered in fixed dose combinations (FDC).
      DESIGN: Cross sectional. SETTING: Tertiary care hospital in Northern India.
      PARTICIPANTS: 79 HIV-infected children receiving antiretroviral therapy with FDCs
      for more than month. INTERVENTION: Two-point sampling (0 and 2 hours after the
      morning dose). OUTCOME MEASURES: Plasma concentrations of all three drugs were
      simultaneously assayed by liquid chromatography/mass spectroscopy. RESULTS:
      Majority (77%) of children were receiving fixed dose combination of stavudine,
      lamivudine, nevirapine in the ratio of 6:30:50 mg. The median (IQR) trough and 2
      hour plasma levels (ug/mL) of nevirapine, stavudine and lamivudine were 5.2 (4.0,
      6.3) and 7.9 (6.0, 9.7); 0.1 (0.06, 0.16) and 1.1 (0.59, 1.6); 0.1 (0.02, 0.2)
      and 2.5 (1.4, 3.1), respectively. Very few children had sub-therapeutic plasma
      drug levels of stavudine (2.5%), lamivudine (7.6%) and nevirapine (10%).
      Inadequate viral suppression at 6 months follow up was significantly associated
      with initial high viral load, low CD4 percentage at the time of enrolment in
      study, and lower doses of lamivudine and stavudine. CONCLUSIONS: The currently
      available generic pediatric fixed dose antiretroviral combinations in India
      provide adequate drug exposure in majority of children.

PMID- 24736908
TI  - Management of neonatal cholestasis: consensus statement of the Pediatric
      Gastroenterology Chapter of Indian Academy of Pediatrics.
AB  - JUSTIFICATION: Neonatal cholestasis is an important cause of chronic liver
      disease in young children. Late referral and lack of precise etiological
      diagnosis are reasons for poor outcome in substantial number of cases in India.
      There is a need to create better awareness among the pediatricians, obstetricians
      and primary care physicians on early recognition, prompt evaluation and referral
      to regional centers. PROCESS: Eminent national faculty members were invited to
      participate in the process of forming a consensus statement. Selected members
      were requested to prepare guidelines on specific issues, which were reviewed by
      two other members. These guidelines were then incorporated into a draft
      statement, which was circulated to all members. A round table conference was
      organized; presentations, ensuing discussions, and opinions expressed by the
      participants were incorporated into the final draft. OBJECTIVES: To review
      available published data on the subject from India and the West, to discuss
      current diagnostic and management practices in major centers in India, and to
      identify various problems in effective diagnosis and ways to improve the overall
      outcome. Current problems faced in different areas were discussed and possible
      remedial measures were identified. The ultimate aim would be to achieve results
      comparable to the West. RECOMMENDATIONS: Early recognition, prompt evaluation and
      algorithm-based management will improve outcome in neonatal cholestasis.
      Inclusion of stool/urine color charts in well baby cards and sensitizing
      pediatricians about differentiating conjugated from the more common unconjugated
      hyperbilirubinemia are possible effective steps. Considering the need for
      specific expertise and the poor outcome in sub- optimally managed cases, referral
      to regional centers is warranted.

PMID- 24736907
TI  - Growth of children with juvenile idiopathic arthritis.
AB  - OBJECTIVE: To evaluate the growth pattern in children with juvenile idiopathic
      arthritis and its subtypes in comparison with age, sex and temporally matched
      controls. STUDY DESIGN: Prospective study. SETTING: Pediatric rheumatology clinic
      of a tertiary care hospital in Eastern part of India. PARTICIPANTS: Seventy-five
      children (2-12 years) diagnosed as juvenile idiopathic erthritis by International
      League of Associations for Rheumatology criteria and 75 age- and sex- matched
      controls. INTERVENTION: Weight, height and body mass index were recorded at six
      monthly interval in both groups over a period of 3 years. MAIN OUTCOME MEASURES:
      weight, height and body mass index. RESULTS: Subtype distribution of juvenile
      idiopathic arthritis was: oligoarthritis (49%, n=37), rheumatoid factor negative
      polyarthritis (27%, n=20), rheumatoid factor positive polyarthritis (8%, n=6),
      systemic onset (15%, n=11) and enthesitis related arthritis (1.3%, n=1).
      Anthropometric parameters in children with juvenile idiopathic arthritis were not
      significant different from controls. Comparison between the subtypes showed
      significant differences in height (P=0.011), weight (P=0.005), and growth
      velocity (P=0.005), but not in body mass index. Systemic onset disease led to
      significant restriction in height (P=0.018; 95% CI 2.13-33.77) and weight
      (P=0.008; 95% CI 1.47-14.43) compared to controls. Growth velocity was
      significantly affected in rheumatoid factor positive polyarthritis (P=0.003; 95%
      CIO. 46-3.14). CONCLUSIONS: Children with juvenile idiopathic arthritis do not
      have significantly lower values of anthropometric parameters compared to
      controls. Significant restriction in height and weight is seen in systemic onset
      disease, and growth velocity is significantly reduced in rheumatoid factor
      positive subjects.

PMID- 24736909
TI  - Pericardial effusion in children: experience from tertiary care center in
      northern India.
AB  - OBJECTIVE: To describe profile and outcome in children with significant
      pericardial effusion. METHODS: Hospital records of 25 children admitted with
      significant pericardial effusion during January 2010 to March 2013 were analyzed.
      RESULTS: Thirteen (52%) children had tubercular, 6 (24%) had bacterial, 3 viral,
      2 recurrent idiopathic and one had malignant pericardial effusion. Only 3
      children in our series required surgical drainage. CONCLUSION: Echocardiography
      guided percutaneous pericardiocentesis and pigtail catheter placement was found
      to be safe and effective.

PMID- 24736910
TI  - A micro-costing model of neonatal intensive care from a tertiary Indian unit:
      feasibility and implications for insurance.
AB  - OBJECTIVE: To calculate and compare costs of neonatal intensive care by micro
      costing and gross-costing methods. METHODS: The costs of resources of a tertiary
      care neonatal intensive care unit were estimated by the two methods to arrive at
      specific costs per diagnosis related categories for 33 neonates followed-up
      prospectively. RESULTS: Gross-costing as compared to micro-costing resulted in
      higher cost per bed (Rs 6315 vs. Rs 4969) and wide variations of costs (-34.8% to
      +13.4%). Intensity of interventions, relative stay in neonatal intensive care
      unit compared to the step-down nursery, and total length of hospital admission
      accounted for these variations. CONCLUSION: Estimates based on micro-costing
      arrived in this study may be used as a starting point in developing assumptions
      for insurance models covering neonatal intensive care.

PMID- 24736911
TI  - Childhood cancer incidence in India: a review of population-based cancer
      registries.
AB  - OBJECTIVES: To summarize and provide an overview of the childhood cancer
      incidence reported in 25 population-based cancer registries of India. METHODS:
      Secondary data on age-adjusted rates of cancer incidence for children (0-14
      years) were collected from the report of the National Cancer Registry Programme
      in the year 2013. range of age-adjusted-rates per million children were tabulated
      for six regions of the country. RESULTS: Age-adjusted cancer incidence rates
      ranged from 18.6 per million to 159.6 per million for boys and 11.3 to 112.4 for
      girls. The highest incidence was observed for males (159.6) in Southern region of
      the country and the lowest in North-east in both boys (18.6) and girls (11.3).
      Leukemia and lymphoma were the commonest malignancies in boys whereas leukemia
      and brain tumors were commonest in girls. CONCLUSION: Childhood cancer incidence
      appears to be increasing in India.

PMID- 24736915
TI  - Pulmonary infection by rapidly growing mycobacterium in an immunocompetent child.
AB  - BACKGROUND: Pulmonary infections by rapidly growing mycobacteria are rare in
      immunocompetent children. CASE CHARACTERISTICS: A 2-year-old boy with persistent
      right upper lobe pneumonia. OBSERVATION: Bronchoalveolar lavage culture
      demonstrated growth of Mycobacterium atocessus. OUTCOME: Complete resolution of
      disease with multidrug chemotherapy with imipenam, clarithromycin and amikacin.
      MESSAGE: Persistent upper lobe cavitory lesions can rarely be caused by rapidly
      growing mycobacteria.

PMID- 24736916
TI  - Disseminated cryptococcosis.
AB  - BACKGROUND: Fungal infections, especially in immunocompetent children are
      uncommon causes of fever of unknown origin. CASE CHARACTERISTICS: A 5-year-old
      boy with prolonged fever and no evidence of immunosuppression. OBSERVATION:
      Ultrasound-guided retroperitoneal lymph node biopsy showed granulomas and
      intracytoplamic fungal yeasts; staining charactristics were suggestive of
      cryptococci. Clinical and radiological improvement was seen after treatment with
      amphoterecin-B. OUTCOME: Disseminated fungal infection should be suspected as a
      cause of pyrexia of unknown origin after ruling out the commoner causes. Biopsy
      from enlarged lymph node or organomegaly may yield the diagnosis when non
      invasive tests fail.

PMID- 24736917
TI  - Ventricular tachycardia due to perinatal asphyxia.
AB  - BACKGROUND: Perinatal asphyxia is known to precipitate myocardial dysfunction,
      rhythm abnormalities and congestive cardiac failure. CASE CHARACTERISTICS: A 2
      day old neonate with perinatal asphyxia. OBSERVATION: He developed shock
      secondary to ventricular tachycardia, and required synchronized cardioversion for
      reversion of abnormal rhythm. OUTCOME: Reversal of arrhythmia leading to
      recovery. MESSAGE: Early identification and management of ventricular tachycardia
      in neonate with perinatal asphyxia can be life-saving.

PMID- 24736918
TI  - A new classification for conference delegates!

PMID- 24736919
TI  - Nucleated RBC count as predictor of neurological outcome in perinatal asphyxia.
AB  - The immediate and short term outcomes of term newborns with perinatal asphyxia
      were studied in relation to the nucleated red blood cell count at admission. The
      mean (SD) NRBC/100WBC (white blood cells) was significantly higher in sequelae
      group than normal [9.8 (98.9) vs. 2.9 (43); P=0.001].

PMID- 24736920
TI  - Improving AEFI surveillance in India.

PMID- 24736921
TI  - Donkeys milk feeding in newborn: myths and facts.

PMID- 24736922
TI  - Diabetic ketoacidosis with normal anion gap--to use or not to use normal saline?

PMID- 24736923
TI  - Management of bronchiolitis.

PMID- 24736924
TI  - Tdap during pregnancy.

PMID- 24736925
TI  - Outcome of ELBW neonates: a raveling picture.

PMID- 24736926
TI  - Pediatric empyema thoracis--role of conservative management.

PMID- 24736927
TI  - Eruptive lingual papillitis.

PMID- 24736928
TI  - Bullous impetigo.

PMID- 24736929
TI  - A novel mutation in COL2A1 leading to spondyloepiphyseal dysplasia congenita in a
      three-generation family.
AB  - PURPOSE: To investigate the genotype of COL2A1 in a three-generation
      spondyloepiphyseal dysplasia congenita (SEDC) family. METHODS: Five affected
      individuals from a Chinese SEDC family were enrolled in the study. All patients
      underwent thorough physical and radiographic examinations. DNA samples of the
      affected patients and the healthy controls were collected with the informed
      consent obtained from each participant. Two short tandem repeat polymorphic
      markers flanking COL2A1 gene region were detected to determine the haplotype of
      each patient. Subsequently, sequence analysis was performed in COL2A1 gene to
      identify potential genetic mutation. RESULTS: Haplotype analysis showed that the
      same disease-associated haplotype was segregated through the whole pedigree. A
      maximum LOD score of 1.5 was obtained with D12S85 and D12S368. DNA sequence
      analysis revealed a c.1636 G/A transition in exon 25 of the COL2A1 gene, which
      converted the codon GGT for glycine at position 546 to AGT, a codon for serine.
      The patients were all heterozygous for the mutation G546S, which was absent in
      either of the unaffected family members or of the normal individuals.
      CONCLUSIONS: This is the first familial report of G546S mutation in the COL2A1
      gene that results in SEDC. Although great achievements have been made in the
      recognition of the mutation spectrum, more intensive studies are warranted to
      further identify correlations between genotype and phenotype.

PMID- 24736930
TI  - Surgical technique and effectiveness of microendoscopic discectomy for large
      uncontained lumbar disc herniations: a prospective, randomized, controlled study
      with 8 years of follow-up.
AB  - BACKGROUND: There is a long-held concept among spine surgeons that endoscopic
      lumbar discectomy procedures are reserved for small-contained disc herniation; 8
      year follow-up has not been reported. The purpose of this study is to assess
      microendoscopic discectomy (MED) in patients with large uncontained lumbar disc
      herniation (the antero-posterior diameter of the extruded fragment is 6-12 mm or
      more on axial cuts of MRI) and report long-term outcome. METHODS: One hundred
      eighty-five patients with MED or standard open discectomy underwent follow-up for
      8 years. Primary (clinical) outcomes data included Numerical Rating Scale (NRS)
      for back and leg symptoms and Oswestry Disability Index (ODI) to quantify pain
      and disability, respectively. Secondary (objective) outcomes data included
      operative time, blood loss, postoperative analgesics, length of hospital stay,
      time to return to work, reoperation and complication rate, patient satisfaction
      index (PSI), and modified (MacNab) criteria. RESULTS: At the end of the follow
      up, the leg pain relief was statistically significant for both groups. NRS back
      pain, ODI, PSI and MacNab criteria showed significant deterioration for control
      group. Secondary outcomes data of MED group were significantly better than the
      control group. CONCLUSIONS: Large, uncontained, lumbar disc herniations can be
      sufficiently removed using MED which is an effective alternative to open
      discectomy procedures with remarkable long-term outcome. Although the
      neurological outcome of the two procedures is the same, the morbidity of MED is
      significantly less than open discectomy. Maximum benefit can be gained if we
      adhere to strict selection criteria. The optimum indication is single- or multi
      level radiculopathy secondary to a single-level, large, uncontained, lumbar disc
      herniation.

PMID- 24736931
TI  - Persistent degenerative changes in the intervertebral disc after burst fracture
      in an in vitro model mimicking physiological post-traumatic conditions.
AB  - PURPOSE: Post-traumatic disc degeneration (DD) is currently investigated with
      models not fully matching the clinical condition, in particular post-traumatic
      loading of the disc is not considered. Therefore, the aim was to establish an in
      vitro burst fracture model that more closely mimics the in vivo situation by
      including post-traumatic physiological loading and to investigate DD under these
      conditions. METHODS: 72 rabbit spinal segments (disc/endplates + 1/3 of adjacent
      vertebrae) were harvested from T8/9 to L5/6 and assigned to control (n = 36) or
      trauma groups (n = 36). Burst fractures were induced at day 0 in the trauma group
      using a dropped-weight device. From day 1 to 28, all specimens were cultured at
      37  degrees C and were dynamically loaded daily (~1 MPa nominal pressure, 1 Hz,
      2,500 cycles). At day 1, 7, 14, and 28, 9 specimens from each group were taken
      for analysis: histology (n = 2), total disc glycosaminoglycan (GAG) content (n =
      3) normalized to DNA, and qPCR of DD marker genes (n = 4) in the nucleus pulposus
      and the annulus fibrosus. RESULTS: Burst fracture with post-traumatic
      physiological loading resulted in a 65 % loss of GAG/DNA by day 28. Histological
      sections confirmed the remodeling of the matrix. Catabolic (MMP-1/-3), pro
      apoptotic (TNF-alpha, fas ligand), and pro-inflammatory (IL-1/-6, iNOS) gene
      transcription was substantially up-regulated in the nucleus after the trauma and
      did not normalize to control within 28 days. Similar results were found for the
      annulus on lower levels. CONCLUSION: An in vitro burst fracture model with
      physiological post-traumatic loading was established. Under these conditions,
      burst spinal segments undergo strong and persistent degenerative changes.

PMID- 24736932
TI  - DAIRRy-BLUP: a high-performance computing approach to genomic prediction.
AB  - In genomic prediction, common analysis methods rely on a linear mixed-model
      framework to estimate SNP marker effects and breeding values of animals or
      plants. Ridge regression-best linear unbiased prediction (RR-BLUP) is based on
      the assumptions that SNP marker effects are normally distributed, are
      uncorrelated, and have equal variances. We propose DAIRRy-BLUP, a parallel,
      Distributed-memory RR-BLUP implementation, based on single-trait observations (
      Y: ), that uses the Average Information algorithm for restricted maximum
      likelihood estimation of the variance components. The goal of DAIRRy-BLUP is to
      enable the analysis of large-scale data sets to provide more accurate estimates
      of marker effects and breeding values. A distributed-memory framework is required
      since the dimensionality of the problem, determined by the number of SNP markers,
      can become too large to be analyzed by a single computing node. Initial results
      show that DAIRRy-BLUP enables the analysis of very large-scale data sets (up to
      1,000,000 individuals and 360,000 SNPs) and indicate that increasing the number
      of phenotypic and genotypic records has a more significant effect on the
      prediction accuracy than increasing the density of SNP arrays. 

PMID- 24736933
TI  - [Diagnosis of systolic and diastolic heart failure].
AB  - In this review, heart failure is confined to etiologies not due to rhythm
      disturbances or valvular heart disease. Besides measurement of natriuretic
      peptides, echocardiography is established as an important diagnostic procedure.
      Echocardiography is especially helpful in discriminating between heart failure
      with preserved ejection fraction (HF-PEF) and reduced ejection fraction (HF-REF).
      Because of its ease to be performed, the 6 min walk test continues to be a
      standard diagnostic procedure. Cardiopulmonary exercise testing provides more
      detailed information regarding differential diagnostic and prognostic
      considerations. 

PMID- 24736934
TI  - [Resistant arterial hypertension and a prominent sternum in a 77-year-old woman].
AB  - The case of a 77-year-old woman who was admitted with resistant arterial
      hypertension is reported. In view of a history of pheochromocytoma 2 years ago,
      catecholamine levels were examined and found to be elevated; in addition, MIBG
      scintigraphy showed a positive area in the anterior mediastinum. Computer
      tomography showed a tumor in the sternum. Histology confirmed metastasis from the
      pheochromocytoma, and the corpus was removed surgically. Currently, the patient
      is without any evidence of relapse. 

PMID- 24736935
TI  - The powers of participatory medicine.

PMID- 24736937
TI  - [The seriously affected stroke patient who is not able to communicate - treatment
      to the best of one's knowledge and ethical principles].
AB  - Choosing the right therapy for a patient affected by a severe stroke that
      resulted in communicative inability is a real challenge for an interdisciplinary
      team. In the following case prognostic predictors will be investigated and
      ethical issues for a better decision making will be discussed. 

PMID- 24736936
TI  - Activation of auditory white matter tracts as revealed by functional magnetic
      resonance imaging.
AB  - INTRODUCTION: The ability of functional magnetic resonance imaging (fMRI) to
      detect activation in brain white matter (WM) is controversial. In particular,
      studies on the functional activation of WM tracts in the central auditory system
      are scarce. We utilized fMRI to assess and characterize the entire auditory WM
      pathway under robust experimental conditions involving the acquisition of a large
      number of functional volumes, the application of broadband auditory stimuli of
      high intensity, and the use of sparse temporal sampling to avoid scanner noise
      effects and increase signal-to-noise ratio. METHODS: Nineteen healthy volunteers
      were subjected to broadband white noise in a block paradigm; each run had four
      sound-on/off alternations and was repeated nine times for each subject. Sparse
      sampling (TR=8 s) was used. RESULTS: In addition to traditional gray matter (GM)
      auditory center activation, WM activation was detected in the isthmus and midbody
      of the corpus callosum (CC), tapetum, auditory radiation, lateral lemniscus, and
      decussation of the superior cerebellar peduncles. At the individual level, 13 of
      19 subjects (68 %) had CC activation. Callosal WM exhibited a temporal delay of
      approximately 8 s in response to the stimulation compared with GM. CONCLUSIONS:
      These findings suggest that direct evaluation of the entire functional network of
      the central auditory system may be possible using fMRI, which may aid in
      understanding the neurophysiological basis of the central auditory system and in
      developing treatment strategies for various central auditory disorders.

PMID- 24736938
TI  - Public health in Austria: a snapshot.

PMID- 24736939
TI  - Design of molecular beacons: 3' couple quenchers improve fluorogenic properties
      of a probe in real-time PCR assay.
AB  - Convenient preparation of fluorogenic hairpin DNA probes (molecular beacons)
      carrying a pair of FAM fluorophores (located close to 5'-terminus of the probe)
      or a pair of BHQ1 quenchers on 3'-terminus (with (BHQ1)2 or BHQ1-BHQ1
      composition) is reported. These probes were used for the first time in a real
      time PCR assay and showed considerable improvements in fluorogenic properties
      (the total fluorescence increase or signal-to-background ratio) in assay
      conditions vs. conventional one-FAM-one-BHQ1 molecular beacon probes as well as
      vs. hydrolyzable one-FAM-one-BHQ1 TaqMan probes. At the same time, such multiple
      modifications of the probe do not influence its Cq (a fractional PCR cycle used
      for quantification). The probe MB14 containing a BHQ1-BHQ1 pair showed a PCR
      fluorescence/background value of 9.6 which is more than two times higher than
      that of a regular probe MB2 (4.6). This study demonstrates prospects for the
      design of highly fluorogenic molecular beacon probes suitable for quantitative
      real-time PCR and for other potential applications (e.g. intracellular RNA
      detection and SNP/mutation analysis). 

PMID- 24736940
TI  - Differences in the Spatial Variability Among CO2, CH 4, and N 2O Gas Fluxes from
      an Urban Forest Soil in Japan.
AB  - The spatial variability of carbon dioxide (CO(2)), methane (CH(4)), and nitrous
      oxide (N(2)O) fluxes from forest soil with high nitrogen (N) deposition was
      investigated at a rolling hill region in Japan. Gas fluxes were measured on July
      25th and December 5th, 2008 at 100 points within a 100 * 100 m grid. Slope
      direction and position influenced soil characteristics and site-specific
      emissions were found. The CO(2) flux showed no topological difference in July,
      but was significantly lower in December for north-slope with coniferous trees.
      Spatial dependency of CH(4) fluxes was stronger than that of CO(2) or N(2)O and
      showed a significantly higher uptake in hill top, and emissions in the valley
      indicating strong influence of water status. N(2)O fluxes showed no spatial
      dependency and exhibited high hot spots at different topology in July and
      December. The high N deposition led to high N(2)O fluxes and emphasized the
      spatial variability.

PMID- 24736941
TI  - Optic nerve glioma: an update.
AB  - Optic nerve glioma is the most common optic nerve tumour. However, it has an
      unpredictable natural history. The treatment of optic nerve gliomas has changed
      considerably over the past few years. Chemotherapy and radiation therapy can now
      stabilize and in some cases improve the vision of patients with optic nerve
      gliomas. The treatment of optic nerve glioma requires a multi-disciplinary
      approach where all treatment options may have to be implemented in a highly
      individualized manner. The aim of this review article is to present current
      diagnostic and treatment protocols for optic nerve glioma. 

PMID- 24736942
TI  - Protective effects of ginseng leaf extract using enzymatic extraction against
      oxidative damage of UVA-irradiated human keratinocytes.
AB  - UVA is responsible for numerous biological effects on the skin, including
      premature aging characterized by wrinkles, leathery texture, and mottled
      pigmentation. The objective of this study was evaluating the protective effect of
      ginseng leaf extract prepared by Ultraflo L on skin from photodamage. Anti
      wrinkle effect of ginseng leaf extract with or without Ultraflo L treatment were
      tested on human keratinocyte cells (HaCaT) irradiated with ultraviolet (UV) A.
      Ginseng leaves inhibited ROS generation, GHS depletion, and expression of MMP-2
      and MMP-9 induced by UVA irradiation. The glutathione (GSH) content of the cells
      was significantly increased by over 25 MUg mL(-1) of Ultraflo-treated extract
      (UTGL) as well as by over 100 MUg mL(-1) of nonenzyme-treated extract (NEGL)
      compared to control. UTGL and NEGL treatments significantly decreased expression
      of metalloproteinase (MMP)-2 and 9 compared with control, but inhibitory effects
      of two groups on expression of MMPs were not significantly different. Overall,
      ULtraflo L-treated ginseng leaves inhibited ROS generation, GHS depletion, and
      expression of MMP-2 and MMP-9 in UVA photodamaged HaCat cells. From these
      results, enzyme-treated ginseng leaf extract has advantages over untreated
      ginseng leaves and have potential as a skin protective ingredient against UVA
      induced photodamage. 

PMID- 24736943
TI  - Retraction Note: Transcatheter closure of perimembranous ventricular septal
      defects (VSD) with VSD occluder: early and mid-term results.

PMID- 24736944
TI  - Incidence of periodontitis in Japanese patients with cardiovascular diseases: a
      comparison between abdominal aortic aneurysm and arrhythmia.
AB  - Although there is a link between periodontitis and cardiovascular disease (CVD),
      the influence of periodontitis on CVD is unclear. The aim of this study was to
      assess the relationship between periodontal bacterial burden and CVD. We studied
      142 patients with tachyarrhythmia (TA) and 25 patients with abdominal aortic
      aneurysm (AAA). We examined periodontitis and the presence of Porphyromonas
      gingivalis, Aggregatibacter actinomycetemcomitans and Prevotella intermedia in
      the patients' saliva and subgingival plaque using PCR. We also measured serum
      antibody titers against the pathogens using ELISA. We found that the patients
      with AAA had fewer remaining teeth (14.6 +/- 2.0 vs. 20.9 +/- 0.7, P < 0.05) and
      deeper pocket depth (3.01 +/- 0.26 vs. 2.52 +/- 0.05 mm, P < 0.05) compared to
      the TA patients. The existence of each periodontal bacterium in their saliva or
      subgingival plaque and serum antibody titers was comparable between the two
      groups. Periodontitis may have a larger affect on aneurysm progression compared
      to arrhythmia. 

PMID- 24736945
TI  - Dipeptidyl peptidase-4 inhibitors are associated with improved left ventricular
      diastolic function after acute myocardial infarction in diabetic patients.
AB  - Dipeptidyl peptidase-4 (DPP4) is an integral membrane glycoprotein that modulates
      the pathological state of diabetes mellitus (DM), and DPP4 inhibitors are a new
      class of anti-type-2 DM drugs. Recent preclinical studies have associated DPP4
      inhibition with improved myocardial systolic and diastolic function. Based on
      preclinical findings, we investigated associations between the administration of
      DPP4 inhibitors and cardiac function after acute myocardial infarction (AMI) in a
      clinical setting. We enrolled 34 patients with diabetes who were treated for
      acute myocardial infarction at our hospital between January 2010 and December
      2012. We retrospectively compared changes in cardiac parameters determined by
      trans-thoracic echocardiography between patients treated with (DPP4-I group; n =
      13) or without (non-DPP4-I group; n = 21) a DPP4 inhibitor during follow-up. The
      values of E/e' and of e'/a' significantly decreased and increased, respectively,
      in the DPP4-I, compared with the non-DPP4-I group (-2.53 +/- 5.53 vs. 2.58 +/-
      5.68, p = 0.038 and 0.08 +/- 0.23 vs. -0.12 +/- 0.21, p = 0.036, respectively).
      We concluded that DPP4 inhibitors could improve E/e' and e'/a' in patients with
      DM and AMI and thus might be effective for treating left ventricular diastolic
      failure. 

PMID- 24736946
TI  - Cardiac dysfunction and orthostatic intolerance in patients with myalgic
      encephalomyelitis and a small left ventricle.
AB  - The etiology of chronic fatigue syndrome (CFS) is unknown. Myalgic
      encephalomyelitis (ME) has been recently postulated to be the cause of CFS.
      Orthostatic intolerance (OI) has been known as an important symptom in predicting
      quality of life in CFS patients. Cardiac function may be impaired in patients
      with ME. The presence or absence of OI was determined both symptomatically and by
      using a 10-min stand-up test in 40 ME patients. Left ventricular (LV) dimensions
      and function were determined echocardiographically in the ME patients compared to
      40 control subjects. OI was noted in 35 (97%) of the 36 ME patients who could
      stand up quickly. The mean values for the cardiothoracic ratio, systemic systolic
      and diastolic pressures, LV end-diastolic diameter (EDD), LV end-systolic
      diameter, stroke volume index, cardiac index and LV mass index were all
      significantly smaller in the ME group than in the controls. Both a small LVEDD
      (<40 mm, 45 vs. 3%) and a low cardiac index (<2 l/ min/mm2, 53 vs. 8%) were
      significantly more common in the ME group than in the controls. Both heart rate
      and LV ejection fraction were similar between the groups. In conclusion, a small
      LV size with a low cardiac output was common in ME patients, in whom OI was
      extremely common. Cardiac dysfunction with a small heart appears to be related to
      the symptoms of ME.

PMID- 24736947
TI  - Conserved oncogenic behavior of the FAM83 family regulates MAPK signaling in
      human cancer.
AB  - FAM83B (family with sequence similarity 83, member B) was recently identified as
      a novel oncogene involved in activating CRAF/MAPK signaling and driving
      epithelial cell transformation. FAM83B is one of eight members of a protein
      family (FAM83) characterized by a highly conserved domain of unknown function
      (DUF1669), which is necessary and sufficient to drive transformation. Here, it is
      demonstrated that additional FAM83 members also exhibit oncogenic properties and
      have significantly elevated levels of expression in multiple human tumor types
      using a TissueScan Cancer Survey Panel PCR array and database mining.
      Furthermore, modeling the observed tumor expression of FAM83A, FAM83C, FAM83D, or
      FAM83E promoted human mammary epithelial cell (HMEC) transformation, which
      correlated with the ability of each FAM83 member to bind CRAF (RAF1) and promote
      CRAF membrane localization. Conversely, ablation of FAM83A or FAM83D from breast
      cancer cells resulted in diminished MAPK signaling with marked suppression of
      growth in vitro and tumorigenicity in vivo. Importantly, each FAM83 member was
      determined to be elevated in at least one of 17 distinct tumor types examined,
      with FAM83A, FAM83B, and FAM83D most frequently overexpressed in several diverse
      tissue types. Finally, evidence suggests that elevated expression of FAM83
      members is associated with elevated tumor grade and decreased overall survival.
      IMPLICATIONS: FAM83 proteins represent a novel family of oncogenes suitable for
      the development of cancer therapies aimed at suppressing MAPK signaling.

PMID- 24736948
TI  - Ultrasound-targeted microbubble destruction combined with dual targeting of HSP72
      and HSC70 inhibits HSP90 function and induces extensive tumor-specific apoptosis.
AB  - The specific and efficient delivery of small interfering RNA (siRNA) into cancer
      cells in vivo remains a major obstacle. In this study, we investigated whether
      ultrasound-targeted microbubble destruction (UTMD) combined with dual targeting
      of HSP72 and HSC70 in prostate cancer cell lines improve the specific and
      efficient cell uptake of siRNA, inhibit HSP90 function and induce extensive tumor
      specific apoptosis. VCaP cells were transfected with siRNA oligonucleotides. Cell
      viability assays were used to evaluate the safety of UTMD. The expression of
      HSP70, HSP90, caspase-8, caspase-3, PARP-1 and cleaved caspase-3 were determined
      by quantitative PCR and western blotting. Apoptosis and transfection efficiency
      were detected by flow cytometry. We found that HSP72, HSC70 and HSP90 expression
      was absent or weak in normal prostate epithelial cells (RWPE-1), and became
      uniformly and strongly expressed in prostate cancer cells (VCaP). VCaP and RWPE-1
      cells expressed very low levels of caspase-8, caspase-3, PARP-1 and cleaved
      caspase-3. UTMD combined with dual targeting of HSP72 and HSC70 siRNA impoved the
      efficiency of transfection, cell uptake of siRNA, downregulated HSP70 and HSP90
      expression in VCaP cells on the mRNA and protein levels, and upregulated major
      apoptotic markers (PARP-1, caspase-8, caspase-3 and cleaved caspase-3), thus,
      inducing extensive tumor-specific apoptosis. The Cell Counting Kit-8 assay showed
      decreased cellular viability in the HSP72/HSC70-siRNA silenced group. These
      results suggest that the combination of UTMD with dual targeting of HSP72 and
      HSC70 may improve the specific and efficient cell uptake of siRNA, inhibit HSP90
      function and induce extensive tumor-specific apoptosis, indicating a novel,
      potential means for targeting therapeutic strategy to prostate cancer cells. 

PMID- 24736949
TI  - Drug Interaction Between Oral Cyclosporine Modified and Iron.
AB  - OBJECTIVE: To describe a recent case of suspected interaction between oral
      cyclosporine modified and iron. CASE SUMMARY: A 33-year-old man underwent urgent
      cardiac transplantation for refractory cardiogenic shock caused by acute
      myocarditis. The patient had persistently low levels of cyclosporine despite a
      dose increase of the drug after the change of administration route from
      intravenous to oral. Spacing the administration of cyclosporine modified from
      oral iron resolved the problem. This drug interaction was reported as "probable"
      as determined by a Drug Interaction Probability Scale score of 7. Using this
      scoring system, the patient experienced a probable drug interaction between
      cyclosporine and iron both administered orally, and we surmise that the mechanism
      is that iron physicochemically destabilizes the cyclosporine microemulsion when
      both are administered concurrently. DISCUSSION: This may be because of the
      interaction between cyclosporine microemulsion and iron because this cation can
      destabilize the immunosuppressant dosage form. CONCLUSIONS: Taking into account
      that joint administration of oral iron and cyclosporine modified can generate a
      physicochemical interaction that involves a decrease in the absorption of
      cyclosporine modified, we believe that it is necessary to recommend spacing
      administrations of both drugs as well as monitoring levels of cyclosporine in
      order to ensure optimal levels of immunosuppression.

PMID- 24736950
TI  - Fidelity of implementation of an evidence-based HIV prevention program among
      Bahamian sixth grade students.
AB  - The Bahamian Ministry of Education has elected to implement at a national level
      in all Bahamian government grade six classes an evidence-based HIV prevention
      intervention [Focus on Youth in the Caribbean (FOYC)]. This study explores
      fidelity of implementation of the intervention, factors that may influence
      implementation fidelity, and the impact of variations in the implementation
      fidelity on student outcomes. Data were collected in the first wave of national
      implementation in 2011, involving 35 government primary schools and 110 teachers
      and 2,811 students. Structural equation modeling was performed to examine the
      relationships among factors which facilitated or impeded teachers' implementation
      of FOYC. Results indicate that teachers taught 16.3 out of 30 core activities,
      24.9 out of 46 total activities, and 4.4 out of 8 sessions on average. The
      strongest predictor of implementation fidelity was teacher comfort level with the
      FOYC curriculum. Teachers who did not perceive the FOYC intervention to be
      important for their students or who had attended only part of a FOYC training
      workshop were more likely to change the curriculum. Increased duration of
      experience as a teacher (>10 years) was negatively associated with fidelity of
      implementation. Teacher's perception of the importance of the FOYC intervention
      and implementation fidelity had direct positive effects on students' HIV/AIDS
      knowledge, reproductive health skills, protective intentions, and self-efficacy.
      Youth did not appear to benefit from FOYC if two or fewer sessions were
      delivered. We concluded that an evidence-based HIV prevention intervention can be
      implemented at a national level. Prior training of teachers in the intervention
      curriculum, teacher perception of the importance of the intervention, and fewer
      years as a teacher are associated with implementation fidelity. Implementation
      fidelity is associated with improved student outcomes.

PMID- 24736951
TI  - Observational measures of implementer fidelity for a school-based preventive
      intervention: development, reliability, and validity.
AB  - Current measures of implementer fidelity often fail to adequately measure core
      constructs of adherence and competence, and their relationship to outcomes can be
      mixed. To address these limitations, we used observational methods to assess
      these constructs and their relationships to proximal outcomes in a randomized
      trial of a school-based preventive intervention (Rochester Resilience Project)
      designed to strengthen emotion self-regulation skills in first-third graders with
      elevated aggressive-disruptive behaviors. Within the intervention group (n =
      203), a subsample (n = 76) of students was selected to reflect the overall
      sample. Implementers were 10 paraprofessionals. Videotaped observations of three
      lessons from year 1 of the intervention (14 lessons) were coded for each
      implementer-child dyad on adherence (content) and competence (quality). Using
      multilevel modeling, we examined how much of the variance in the fidelity
      measures was attributed to implementer and to the child within implementer. Both
      measures had large and significant variance accounted for by implementer
      (competence, 68 %; adherence, 41 %); child within implementer did not account for
      significant variance indicating that ratings reflected stable qualities of the
      implementer rather than the child. Raw adherence and competence scores shared 46
      % of variance (r = .68). Controlling for baseline differences and age, the amount
      (adherence) and quality (competence) of program delivered predicted children's
      enhanced response to the intervention on both child and parent reports after 6
      months, but not on teacher report of externalizing behavior. Our findings support
      the use of multiple observations for measuring fidelity and that adherence and
      competence are important components of fidelity which could be assessed by many
      programs using these methods.

PMID- 24736952
TI  - [Why Civitavecchia district, well-known for its high levels of chronic pollution,
      is not included in the SENTIERI project?].

PMID- 24736953
TI  - [SENTIERI method is to be extended to all severely polluted sites].

PMID- 24736954
TI  - [There is anyone who controls the truth of the information about health offered
      by the web?].

PMID- 24736955
TI  - [Markers and quality of care: a comparison between epidemiology and clinical
      medicine].

PMID- 24736956
TI  - [Sustainability of the Italian National Health Service and need of change].

PMID- 24736957
TI  - [Competition for effectiveness and equity in the Italian National Health
      Service].

PMID- 24736958
TI  - [A set of indicators to monitor the adherence to the guidelines for the diagnosis
      and treatment of breast cancer].
AB  - OBJECTIVES: to present a set of indicators developed from six Local Health
      Authorities of the Lombardy Region to monitor the diagnostic and therapeutic
      pathway of breast cancer patients, applied to 2007-2009 incident cases. DESIGN:
      retrospective cohort study. SETTING AND PARTICIPANTS: all subjects with primary
      breast cancer, incident in the period 2007-2009, and collected by cancer
      registries of Milano 1, Bergamo, Cremona, Milano, Milano 2 and Monza-Brianza
      (5,320,272 inhabitants) were included. MAIN OUTCOME MEASURES: through the use of
      combined current health databases (health registry, hospitalizations, outpatient,
      pharmaceutical prescription and specific database for anticancer drugs), for each
      incident case 34 different indicators have been developed to measure the
      appropriateness of the procedures provided for diagnosis, treatment (surgical and
      medical) and follow-up. For each indicator, we analyzed the relationship with
      age, stage, deprivation index, type of treatment, volume of the specific
      procedure of the hospital where primary surgery was performed. Estimates were
      adjusted using multilevel regression models. RESULTS: 12,988 incident cases,
      without metastatic diseases and other cancers, were included in the cohort: 62%
      were localized to the breast, 33% to the axillary lymph-nodes, 3% metastatic ab
      initio, and 2% with unknown stage. Deviations from the expected value of
      different magnitude depending on the type of indicator were observed: the most
      important differences were detected for the follow-up indicators. There was, in
      fact, an excess of several procedures in the first year of follow-up: 75% of the
      cases performed a dosage of a tumor marker, 67% an ecography or a CT scan or an
      MR, and 37% a bone scan. On the other hand, the access to neoadjuvant and
      adjuvant treatments in older women was far below the expected values.
      CONCLUSIONS: the study presents data derived from a large cohort of population
      cases; the set of indicators was validated by a board of oncologists. The use of
      indicators calculated by linking the cancer registries (that provide staging) and
      administrative databases allows the assessment of compliance to the guidelines
      for diagnosis and treatment of tumours. This experience shows that it is possible
      to develop a methodology, shared with clinicians, to define indicators that
      measure the distance between guidelines and current clinical practice in order to
      decrease variability, to limit inappropriateness, and to reduce unnecessary
      diagnostic tests for patients (and, consequently, hospitals organizational
      overload). In order to be sustainable and equitable, a health care system must be
      able to ensure implementation of protocols/procedures based exclusively on the
      best available scientific evidences.

PMID- 24736959
TI  - [Burden of disease attributable to road traffic accidents in the Friuli Venezia
      Giulia Region (Northeastern Italy)].
AB  - OBJECTIVE: to estimate the health impact of road traffic accidents in the Friuli
      Venezia Giulia Region, Northeastern Italy. DESIGN: burden of disease (BoD) study.
      SETTING AND PARTICIPANTS: we used data on road traffic accidents collected by the
      Police in the Friuli Venezia Giulia in 2010 and health data regarding Emergency
      Room visits, hospital admissions, and deaths. MAIN OUTCOME MEASURES: we
      calculated the Disability Adjusted Life Years (DALY) lost because of road traffic
      accidents. The kernel density of the DALYs in the region was analyzed and mapped.
      RESULTS: it was estimated that 3,861 DALYs were lost in 2010. Years lost because
      of premature deaths outnumbered those lost because of disability. The highest
      number of DALYs was lost among 15-44-year-old males. Of 14,361 injured persons
      included in the analysis, only 4,357 were found in the Police database. However,
      these injuries accounted for 95% of all the DALYs. CONCLUSION: the present study
      identified population subgroups with a particularly high impact of road traffic
      accidents. Educational and Police interventions to prevent accidents should be
      addressed to those subgroups. In the future, repeating this analysis will allow
      an evaluation of the effectiveness of preventive interventions in terms of health
      gains.

PMID- 24736960
TI  - [Preventing cardiovascular diseases through a screening modelling applicable to
      wide population groups: results from the first phase of the project].
AB  - OBJECTIVE: evaluate, through active call, lifestyles of an asymptomatic
      population in order to identify hyperglycaemic subjects and/or high-blood
      pressure sufferers to dispatch to their GP to perform suitable checking, and
      subjects to invite to a cardiovascular disease prevention programme because of
      their lifestyles. SETTING AND PARTICIPANTS: between January 2009 and July 2012,
      all healthy residents in the Local Health Authority of Este (ULSS 17 Este) aged
      45-59 years were invited to join a cardiovascular disease prevention programme.
      DESIGN: all participants were evaluated through an administered lifestyle
      questionnaire. Parameters such as blood pressure (BP), glycaemia, waist
      circumference and body mass index were collected and recorded. Participants also
      received counseling, informational materials on lifestyle and were invited to
      individual or group health promotion initiatives in relation to personal risk
      factors. RESULTS: among the invited, 55.5% (3,922/7,071) adhered. Women (58.8%)
      responded significantly better than men (51.9%) (p <0,01). Subjects without risks
      factors were 16.7%. Subjects with lifestyle risk factors but normal BP and
      glycaemia were 49.4%, while those adding altered values for BP and glycaemia were
      25.2%. The 8.6% of the respondents were not eligible for the study. CONCLUSIONS:
      the preliminary results suggest that a preventive programme based on the citizens
      active call by the Department of Prevention could be an effective tool to
      identify asymptomatic individuals with unknown hypertension and/or hyperglycaemia
      and to offer lifestyle interventions to lower the risk of cardiovascular
      diseases.

PMID- 24736961
TI  - [Mortality for accident in Tuscany Region (Central Italy) in immigrants from
      countries at high migration rates].
AB  - OBJECTIVE: to examine the characteristics and mortality trends for specific type
      of accident in immigrants resident in Tuscany and to compare them to those
      observed in Italians resident in the same region. DESIGN: descriptive study using
      the data of the Regional Mortality Registry of Tuscany. SETTING AND PARTICIPANTS:
      1997-2008 deaths for accidents by citizenship ("Italians" and "Immigrants" from
      Countries with strong migratory pressure or PFPM) in residents in Tuscany. MAIN
      OUTCOME MEASURES: number of deaths, proportional mortality and standardized
      (standard: European population) mortality 15-64 truncated rates per 100,000 for
      each specific accidental cause of death, by gender and population (PFPM and
      Italians), in 1997-2008, and confidence intervals at 95% (95%CI); trends in
      mortality standardized truncated rates for specific accidental cause in
      immigrants and Italians in 2002-2008. RESULTS: in the period 1997-2008, 315
      deaths for accidents have been registered in immigrants. The comparison between
      immigrants and Italians did not reveal any significant difference in mortality
      for road and at work accidents. Suicides are significantly higher in Italian
      males (rate in Italians 9.3; 95%CI 8.7-10.0 vs. rate in PFPM 4.3; 95%CI 2.4-6.2),
      while homicides are higher in male immigrants (rate in Italians 0.6; IC95% 0.4
      0.8 vs. rate in PFPM 3.2 95%CI 1.7-4.7). Deaths from other injuries are more
      frequent in Italians in both genders. Trends in mortality rates indicate a
      reducing gap between immigrants and Italians. CONCLUSION: in Tuscany, mortality
      rates for some specific accidental causes are significantly different between
      immigrants and Italians, nevertheless trends of the last evaluated period seem to
      reveal a reducing gap suggesting a progressive integration of immigrants.

PMID- 24736962
TI  - [National Guidelines System: the Italian experience].
AB  - The Italian's experience of the guidelines development group is discussed through
      the evaluation of its ten years of activity. Focus is placed on the Italian
      guidelines working group organization and on the kind of documents developed. The
      horizontal architecture of the system and the several partnerships settled over
      time allowed the definition of a small coordinating group connected with a
      multitude of territorial stakeholders, such as scientific societies and local
      health units pertaining to the Italian National Health System. Different kinds of
      documents were produced, as adaptations of already existing guidelines elaborated
      by international institutions, short reviews addressing specific clinical issues
      and consensus conferences aimed at providing clinical governance on issues which
      lack on evidence. The steps needed to produce a high quality guideline are
      presented, considering and comparing all the different international experiences,
      to define and discuss a common and well-structured methodology, and to face the
      ethical and epistemological implications of each method. The multidisciplinary of
      the working groups, the importance of the active surveillance on conflicts of
      interests, the definition of a minimum set of rules to be followed during the
      whole activity and the transparency of all the steps are the milestones of the
      Italian experience. The lack of a continuous and stable source of funding and the
      subsequent instability of the central structure are endangering all the knowledge
      and the experience gained during these years of activity. It is therefore crucial
      to guarantee and safeguard the role of a national, independent and public
      institution in the supervision of the guidelines development process and the
      provision of clinical governance. 

PMID- 24736963
TI  - [Tobacco farming in Italy receives more funds in comparison to tobacco control].
AB  - In the European Union almost 300,000 tons of raw tobacco are produced every year,
      contributing for 4% of the world production. In Italy, tobacco crop produces
      around 90,000 tons/year and is concentrated in Veneto, Tuscany, Umbria and
      Campania Regions. In 1970, Common Market Organisation provided a virtually
      unlimited support for European tobacco production. After 2004, funds
      progressively has been cut by half, even though the other half has been given for
      restructuring or reconversion of tobacco farms through the Rural Development
      Plan. The Framework Convention on Tobacco Control recommends conversion of
      tobacco crops, although there are no effective measures. Tobacco production
      requires large quantities of chemicals (pesticides, growth regulators,
      fertilisers), with significant workers' exposure if applied without personal
      protective equipments. Pesticides may have genotoxic, teratogenic, immunotoxic,
      hormonal, and carcinogenic effects. Tobacco itself may cause also a disease
      called "Green tobacco sickness" syndrome, as a consequence of nicotine dermal
      absorption due to skin exposure to tobacco leaves. In Italy, financial resources
      for tobacco production and restructuring/conversion to other crops of previously
      tobacco planted fields are available. On the contrary, anti-smoking media
      interventions do not receive funds comparatively relevant as those for tobacco
      production. 

PMID- 24736964
TI  - [In Italians, depression and socioeconomic disadvantage are deeply linked].

PMID- 24736966
TI  - [The New Lancet-UCL Commission].

PMID- 24736965
TI  - [In the last 15 years, survival in Italian children (0-14 years) is increased by
      12%].

PMID- 24736967
TI  - [Genome and microbiome: hologenome. Is epigenetics their link?].

PMID- 24736968
TI  - [On the relationship between change and baseline:regression toward the mean].

PMID- 24736969
TI  - Remote ischemic postconditioning protects the heart by upregulating ALDH2
      expression levels through the PI3K/Akt signaling pathway.
AB  - Remote ischemic postconditioning (RIPostC) has been demonstrated to protect the
      myocardium against ischemia/reperfusion (I/R) injury; however, the mediator and
      underlying mechanisms remain to be elucidated. It has been confirmed that
      aldehyde dehydrogenase 2 (ALDH2) is involved in the remote ischemic
      preconditioning pathway, but whether it is involved in RIPostC remains unknown.
      The aim of the present study was to determine whether increased ALDH2 expression
      levels were involved in the cardioprotective effect evoked by RIPostC via the
      phosphatidylinositol-3-kinase (PI3K)/Akt signaling pathway. Male Sprague Dawley
      rats (n=48) were randomly allocated into the following four groups: Sham group,
      I/R group, RIPostC group, and RIPostC plus wortmannin group (RIPostC+Wort). With
      the exception of the Sham group, the anesthetized rats underwent 45 min of
      coronary artery occlusion followed by 180 min of reperfusion to mimic an I/R
      injury model. Hemodynamic parameters, including the mean arterial pressure and
      heart rate, were recorded, the infarct size was determined and the plasma lactate
      dehydrogenase (LDH) content and creatine kinase (CK) activity levels were
      measured. The expression levels of Bcl-2 and Bax at the mRNA level and ALDH2,
      Akt, phospho-Akt (p-Akt), caspase-3 and cleaved caspase-3 at the protein level in
      the left anterior myocardium were assessed. In the RIPostC group, the infarct
      size was reduced versus that of the I/R group. The plasma LDH content and CK
      activity levels were also reduced. The expression levels of ALDH2 protein were
      elevated, accompanied with increases in the levels of Bcl-2/Bax and p-Akt/Akt and
      a reduction in the levels of cleaved caspase-3. When the PI3K inhibitor
      wortmannin was administered at reperfusion, the p-Akt/Akt ratio was markedly
      reduced and associated with a reduction in the ALDH2 and Bcl-2/Bax levels, and
      the cleaved caspase-3 expression levels were elevated. In conclusion, ALDH2 may
      be an important mediator in the cardioprotection of RIPostC through the PI3K/Akt
      dependent signaling pathway. 

PMID- 24736970
TI  - Gastroschisis-related complications requiring further surgical interventions.
AB  - PURPOSE: The aim of this study was to determine the incidence of gastroschisis
      related complications (GRCs) after closure of the abdominal wall defect, with a
      focus on frequency, type and timing of required surgical interventions, and to
      identify the impact of these on further outcome. METHODS: All gastroschisis
      patients treated from 1975 to 2008 in a tertiary-level center were
      retrospectively reviewed. Surgical procedures for GRCs following abdominal wall
      closure of simple gastroschisis [SG (intact continuous bowel)] and complex
      gastroschisis [CG (additional gastrointestinal malformations)] were compared, and
      outcomes were determined. RESULTS: One hundred and eight patients were identified
      with a median follow-up of 15.0 years (range 4-37). Ninety-four (87%) had SG, and
      14 (13%) CG. Surgical interventions for GRCs were performed in 28 (26%) patients
      with 16 requiring multiple operations. Overall, 60 surgical procedures were
      performed. Bowel obstruction (n = 34) was the most common GRC, followed by
      anastomotic stricture (n = 8) and ischemic bowel (n = 3). The median interval
      between gastroschisis closure and secondary surgery for GRCs was 62.5 days (range
      1 day-15 years). Surgical interventions were significantly more frequent in CG
      compared with SG [12/14 (86%) vs. 16/94 (17%); P < 0.0001]. The overall survival
      rate was 90%. Significantly, more patients required parenteral nutrition for more
      than 28 days [9/28 (32%) vs. 13/80 (16 %); P = 0.0468], longer median time to
      achieve full enteral feedings (87 vs. 33 days; P < 0.0001) and longer median
      hospital stay (117 vs. 54 days; P < 0.0001) compared with those not requiring
      additional surgery. CONCLUSION: GRCs requiring surgical interventions were more
      common in patients with CG, which were associated with delay in achieving full
      enteral feedings and prolonged hospital stay.

PMID- 24736971
TI  - Chronos: stress makes the clock tick.

PMID- 24736972
TI  - Conversion of biosynthetic precursors of RNA to those of DNA by photoredox
      chemistry.
AB  - Soon after the origin of RNA-based life, depletion of prebiotically synthesised
      ribonucleotides would have driven the evolution of a biosynthetic pathway to
      these key building blocks. Ribozyme-catalysed nucleosidation-the key biosynthetic
      step-requires that ribose and the nucleobases are produced by abiotic chemistry
      and are relatively stable to the conditions of their synthesis. The most
      plausible prebiotic synthesis of sugars involves photoreduction of cyanohydrins
      by hydrogen sulphide in the presence of copper(I) cyanide, and we therefore
      subjected ribose to these conditions whereupon it was partially converted to 2
      deoxyribose. Furthermore, a derivative of uracil is reduced under similar
      conditions to thymine. Thus, DNA biosynthetic precursors can be formed
      abiotically from those of RNA allowing for an early evolutionary transition to
      life based on RNA and DNA.

PMID- 24736973
TI  - Histologic findings of recipient corneas obtained via deep anterior lamellar
      keratoplasty.
AB  - PURPOSE: We sought to investigate the histologic findings of recipient corneas
      obtained via deep anterior lamellar keratoplasty (DALK). METHODS: The histology
      of three recipient corneas obtained from patients during DALK was investigated.
      In all cases, the Descemet membrane was successfully exposed without any
      perforation during surgery. The isolated corneal tissue was stained with
      hematoxylin-eosin and periodic acid-Schiff. In two cases, the tissues were
      examined using a transmission electron microscope. RESULTS: In one cornea
      obtained via DALK, only the corneal stroma was observed, and the Descemet
      membrane was not confirmed. In another case, the recipient cornea was detached
      within the Descemet membrane. In the third cornea, the banded layer membrane was
      partially confirmed. CONCLUSIONS: These findings suggest that the recipient
      corneas separated at different layers during the DALK procedure. With our
      surgical technique, the detachment of the Descemet membrane may occur at a
      mechanically weak segment. This separation site may not be between the Descemet
      membrane and the corneal stroma.

PMID- 24736974
TI  - GABA the Hutt.

PMID- 24736976
TI  - The toxic effect of lithium ion on neurons (PC12 cells) and Abeta42 molecules.
AB  - In this study, the neurotoxicity of Li ion and its effect on the morphologies of
      Abeta42 molecules were evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide (MTT) assays, fluorescence (FL), atomic force
      microscopy (AFM), and circular dichroism (CD) spectroscopy. MTT assays show that
      Li ion with a dosage level lower than 50 mg/l did not show detectable
      cytotoxicity on pheochromocytoma (PC12) cells whereas a dosage level higher than
      100 mg/l resulted in significant cytotoxicity. The interaction between Abeta42
      and Li ion occurs, and the quenching effect of Li ion on the fluorescence
      emission of ABeta42 is found to be concentration dependent, suggesting that Li
      ion can bind to the Abeta42 molecules. CD results suggest that a more incompact
      conformation state will be adopted upon the interaction between Abeta42 and Li
      ion. According to AFM images, Li ion could induce the formation of the fibrils
      after incubation for 3 or 5 days. The formation of the oligomer and fibrils
      originates from the strong interactions between Abeta42 and Li ion. Li ion could
      accelerate the random coil Abeta42 monomers aggregating into the beta-sheet
      fibrils, which would induce the neurotoxic effect. 

PMID- 24736975
TI  - Generation of mice encoding a conditional null allele of Gcm2.
AB  - Glial cells missing homolog 2 (GCM2) is a transcription factor that is expressed
      predominately in the pharyngeal pouches and, at later stages, in the developing
      and mature parathyroid glands. In humans, loss of GCM2 function, either through
      recessive apomorphic mutations or dominant inhibitor mutations in the human GCM2
      gene, leads to isolated hypoparathyroidism. In mice, homozygous disruption of
      Gcm2 by conventional gene targeting results in parathyroid aplasia and
      hypoparathyroidism. In this study, we report the generation and functional
      characterization of mice encoding a conditional null allele of Gcm2. We
      demonstrate the functional integrity of the conditional Gcm2 allele and report
      successful in vivo deletion of exon 2 using Cre recombinase. The mice with
      conditional deletion of Gcm2 displayed phenotypes similar to those previously
      described for a conventional Gcm2 knockout, including perinatal lethality,
      hypocalemia, low or undetectable serum levels of parathyroid hormone, and absent
      parathyroid glands. The production of a conditional mutant allele for Gcm2
      represents a valuable resource for the study of the temporal- and spatial
      specific roles for Gcm2, and for understanding the postnatal activities of GCM2
      protein. 

PMID- 24736977
TI  - Pulmonary toxicity in mice following exposure to cerium chloride.
AB  - The widespread application of lanthanoids (Lns) in manufacturing industries has
      raised occupational and environmental health concerns about the possible
      increased health risks to humans exposed to Lns in their working and living
      environments. Numerous studies have shown that exposures to Ln cause pulmonary
      injury in animals, but very little is known about the molecular mechanisms of the
      pulmonary inflammation caused by cerium chloride (CeCl3) exposure. In this study,
      we evaluated the oxidative stress and molecular mechanism underlying with the
      pulmonary inflammation associated with chronic lung toxicity in mice treated with
      nasally instilled CeCl3 for 90 consecutive days. Our findings suggest that
      significant cerium accumulated in the lung, leading the obvious increase of the
      lung indices, significant increases in inflammatory cells and levels of lactate
      dehydrogenase, alkaline phosphate, and total protein, overproduction of reactive
      oxygen species and peroxidation of lipids, reduced antioxidant capacity, and
      pulmonary inflammation. CeCl3 exposure also activated nuclear factor kappaB,
      increased the expression of tumor necrosis factor alpha, cyclooxygenase-2, heme
      oxygenase 1, interleukin 2, interleukin 4, interleukin 6, interleukin 8,
      interleukin 10, interleukin 18, interleukin 1beta, and CYP1A1. However, CeCl3
      reduced the expression of nuclear factor kappaB (NF-kappaB)-inhibiting factor and
      heat shock protein 70. These findings suggest that the pulmonary inflammation
      caused by CeCl3 in mice is closely associated with oxidative stress and
      inflammatory cytokine expression. 

PMID- 24736978
TI  - Mercury levels in raccoons (Procyon lotor) from the Warta Mouth National Park,
      northwestern Poland.
AB  - This is the first report on mercury (Hg) levels in the liver, kidney, skeletal
      muscle, and brain of raccoon in Europe. It studied Hg concentration in 24
      raccoons from the Warta Mouth National Park, northwestern Poland by atomic
      absorption spectroscopy (AAS). The highest total Hg concentrations in the raccoon
      were found in the liver (maximum, 18.45 mg/kg dry weight), while the lowest in
      the brain (maximum, 0.49 mg/kg dw). In adult raccoons, Hg concentrations in the
      liver, kidney, and brain were higher than in immature individuals (p<0.001),
      while similar in skeletal muscle in both age groups. Our results are consistent
      with studies by other authors conducted in North America in areas with similar
      environmental conditions.

PMID- 24736979
TI  - Protective effects of onion extract on cadmium-induced oxidative stress,
      histological damage, and apoptosis in rat heart.
AB  - To date, there is no available information on the protective effect of onion
      (Allium cepa) extract (AcE) on cadmium (Cd)-induced cardiotoxicity. The present
      study was performed to assess the possible antioxidant and anti-apoptotic roles
      of AcE in Cd-induced cardiotoxicity in rats. A Cd group was injected
      subcutaneously with CdCl2 dissolved in saline at a dose of 2 ml/kg/day for 30
      days, resulting in a dosage of 1 mg/kg Cd. The rats in the AcE-treated group were
      given 1 ml of AcE via intragastric intubation for 30 days. The rats intoxicated
      with Cd for 30 days showed increased tissue malondialdehyde (MDA) levels and
      decreased levels of the enzymatic antioxidants superoxide dismutase (SOD),
      glutathione peroxidase (GSH-Px), and catalase (CAT) in cardiac tissue. AcE
      attenuated these adverse effects of Cd. After Cd exposure, histological
      abnormalities were observed, including myofibrillar loss, vacuolization of
      cytoplasm and irregularity of myofibrils. These histological alterations were
      effectively attenuated by the treatment with AcE. Furthermore, our data indicate
      a significant reduction of apoptosis in the cardiomyocytes of the Cd group
      treated with AcE therapy. Animal studies show antioxidant effects of AcE. But to
      date, no study reported the effect of AcE on biochemical and histopathological
      changes due to Cd induced on rat heart. Our study showed that AcE therapy reduced
      Cd-induced oxidative stress and apoptosis, possibly through its antioxidant and
      anti-apoptotic activity. 

PMID- 24736980
TI  - The influence of herbal medicine ursolic acid on the uptake of rosuvastatin
      mediated by OATP1B1*1a and *5.
AB  - Chinese herbal medicines such as hawthorn, salvia, etc., are frequently combined
      with statins so as to treat cardiovascular diseases more effectively. Chinese
      herbal medicines contain many kinds of active components, which may have drug
      drug interactions with statins. This study aims to explore the effect and
      mechanism by which ursolic acid affects OATP1B1-mediated transport of
      rosuvastatin. This study will explore the effect of ursolic acid on OAPT1B1
      mediated transport of rosuvastatin in the different cell systems. Given the
      genetic polymorphisms of OATP1B1, simultaneously, this study will further explore
      the effect of ursolic acid on OATP1B1 (521T>C)-mediated transport of
      rosuvastatin. When the concentration of ursolic acid was 1.8 and 18 uM, it showed
      that ursolic acid significantly inhibits the uptake of rosuvastatin in both
      OATP1B1*1a-HEK 293T cells and OATP1B1*5-HEK 293T cells. The reduction of
      OATP1B1*1a transport of rosuvastatin were 34.60 +/- 2.99 and 66.08 +/- 1.83 %,
      and for OATP1B1*5 were 34.27 +/- 7.08 % and 66.95 +/- 1.14 %. Inhibitory
      parameters of IC50 were 6.25 +/- 0.42 and 6.07 +/- 0.57 uM, respectively. This
      study suggests that ursolic acid can affect the uptake of rosuvastatin in
      hepatocytes by inhibiting the transport of OATP1B1, and gene mutation of OATP1B1
      may cause different effects on its transport of rosuvastatin.

PMID- 24736981
TI  - Proteomic identification of differentially expressed proteins associated with the
      multiple drug resistance in methotrexate-resistant human breast cancer cells.
AB  - Methotrexate (MTX), as a chemotherapeutic drug, is widely used in the therapy of
      several cancer types. The efficiency of drug treatment is compromised by the
      appearance of multidrug resistance (MDR), and the underlying molecular mechanisms
      remain incompletely understood. We investigated the mechanism of MDR in the MTX
      induced breast cancer MCF-7 cells (MCF-7/MTX) using proteomic analysis. MCF-7
      drug-sensitive cells (MCF-7/S) were exposed in progressively increasing
      concentrations of MTX to establish the drug-resistant cell line MCF-7/MTX. The
      biological characteristics of the cells were analyzed by MTT, flow cytometry,
      quantitative PCR, western blotting and the global protein profiles of MCF-7/MTX
      and MCF-7/S were compared using a proteomic approach. The resistance factor of
      MCF-7/MTX cells was 64, and it possessed significant MDR. Seventeen
      differentially expressed proteins between MCF-7/MTX and MCF-7/S cells were
      identified, seven proteins were upregulated and 10 proteins were downregulated in
      MCF-7/MTX cells. We verified that the protein levels of nucleophosmin (NPM),
      alpha-enolase (ENO1) and vimentin (VIM) were upregulated, and heterogeneous
      nuclear ribonucleoprotein (hnRNP C1/C2), phosphoglycerate mutase 1 (PGAM1) and
      proteasome subunit alpha type-2 (PSMA2) were downregulated in MCF-7/MTX cells.
      The mRNA levels of NPM, VIM, hnRNP C1/C2, PGAM1 and PSMA2 were consistent with
      the protein expressions, but the gene expression of ENO1 was slightly
      downregulated. Surprisingly, knockdown of NPM by siRNA sensitized MCF-7/MTX cells
      to MTX and attenuated the multidrug resistance. The proteins identified,
      particularly NPM provides new insights into the mechanism of MDR and is expected
      to become a crucial molecular target for breast cancer treatment.

PMID- 24736982
TI  - Prospective association of childhood receptive vocabulary and conduct problems
      with self-reported adolescent delinquency: tests of mediation and moderation in
      sibling-comparison analyses.
AB  - Associations among receptive vocabulary measured at 4-9 years, mother-reported
      childhood conduct problems at 4-9 years, and self-reported adolescent delinquency
      at 14-17 years were assessed using data from a prospective study of the offspring
      of a large U.S. nationally representative sample of women. A novel quasi
      experimental strategy was used to rule out family-level confounding by estimating
      path-analytic associations within families in a sibling comparison design. This
      allowed simultaneous tests of the direct and indirect effects of receptive
      vocabulary and childhood conduct problems, and of their joint moderation, on
      adolescent delinquency without family-level environmental confounding. The
      significant association of receptive vocabulary with later adolescent delinquency
      was indirect, mediated by childhood conduct problems. Furthermore, a significant
      interaction between receptive vocabulary and childhood conduct problems reflected
      a steeper slope for the predictive association between childhood conduct problems
      and adolescent delinquency when receptive vocabulary scores were higher. These
      findings of significant indirect association were qualitatively identical in both
      population-level and within-family analyses, suggesting that they are not the
      result of family-level confounds. 

PMID- 24736983
TI  - Mechanisms of imitation impairment in autism spectrum disorder.
AB  - Individuals with Autism Spectrum Disorders (ASD) have difficulties with
      imitation, though the nature of these remains unclear. In this study, involving
      28 preschoolers with ASD (M age = 48 months; 90 % male), 17 matched children with
      Global Developmental Delay (GDD group; M age = 44 months; 53 % male) and 17
      typically developing children (TD group, M age = 52 months; 65 % male), we found
      that preschoolers with ASD 1) imitate less frequently than both typically
      developing children and children with GDD; 2) when they do imitate, their
      imitation is less accurate than that of TD children but similar to that of
      children with GDD; 3) unlike participants in both comparison groups, preschoolers
      with ASD use emulation more often than imitation when copying others' actions; 4)
      they spend less time looking at the model's face and more time looking at her
      actions; and 5) attentional, social and executive factors underlie different
      aspects of imitation difficulties in this population. Implications for
      developmental models of autism are discussed. 

PMID- 24736984
TI  - Development of a particle-settling tolerant transmission Raman scheme for
      analysis of suspension samples.
AB  - We have demonstrated a simple and effective strategy, the so-called axial
      illumination scheme, that is able to obtain representative Raman spectra of
      suspension samples with minimal influence from internal particle settling. In a
      partially settled suspension sample, since particle concentrations at given
      points throughout the sample differ, the acquisition of Raman spectra
      representative of the entire sample composition is critically important for
      accurate quantitative analysis. The proposed scheme used axially irradiated laser
      radiation in the same or opposite direction of settling, thus allowing laser
      photons to migrate through the settling-induced particle-density gradient formed
      in the suspension and to widely interact with particles regardless of their
      settled locations. Therefore, transmitted Raman signals gathered opposite to the
      illumination could be more representative of the overall suspension composition
      even with partial settling. In this study, the performance of axial illumination
      schemes (TB (Top-to-Bottom) and BT (Bottom-to-Top) illumination) was evaluated
      for the determination of the aceclofenac (a non-steroidal anti-inflammatory drug)
      concentration in suspensions. Although the spectral features exhibited minute
      variations during settling, settling did not significantly degrade the accuracy
      of the concentration determination, thereby indicating effective acquisition of
      settling-tolerant Raman spectra. In addition, the characteristics of photon
      migration in a partially settled suspension sample were studied using a
      simulation based on Monte-Carlo method. 

PMID- 24736985
TI  - Ecotoxicological effect of sublethal exposure to zinc oxide nanoparticles on
      freshwater snail Biomphalaria alexandrina.
AB  - Freshwater snails are used as sensitive biomarkers of aquatic ecosystem
      pollution. The potential impacts of zinc oxide nanoparticles (ZnONPs) on aquatic
      ecosystems have attracted special attention due to their unique properties. The
      present investigation was designed to evaluate the possible mechanisms of
      ecotoxicological effects of ZnONPs on freshwater snail Biomphalaria alexandrina.
      ZnONPs showed molluscicidal activity against B. alexandrina snails, and the LC50
      was 145 MUg/ml. Two tested concentrations of ZnONPs were selected: The first
      concentration was equivalent to LC10 (7 MUg/ml), and the second was equivalent to
      LC25 (35 MUg/ml). Exposure to ZnONPs (7 and 35 MUg/ml) for three consecutive
      weeks significantly induced malondialdehyde and nitric oxide with concomitant
      decreases in glutathione and glutathione-S-transferase levels in hemolymph and
      soft tissues of treated snails. Moreover, ZnONPs elicited a significant decrease
      in total protein and albumin contents coinciding with enhancement of total lipids
      and cholesterol levels as well as activities of aspartate aminotransferase,
      alanine aminotransferase, and alkaline phosphatase in hemolymph and soft tissues
      of treated snails. This study highlights the potential ecological implications of
      ZnONP release in aquatic environments and may serve to encourage regulatory
      agencies in Egypt to more carefully monitor and regulate the industrial use and
      disposal of ZnONPs.

PMID- 24736986
TI  - Predictive factors for perioperative blood transfusions in laparoscopic
      colorectal surgery.
AB  - BACKGROUND: Allogeneic perioperative blood transfusion (PBT) has been associated
      with higher rates of postoperative complications in patients undergoing
      colorectal surgery and increased tumor recurrence in cancer patients. Our aim is
      to evaluate possible predictive factors for PBT, specifically, in patients
      undergoing laparoscopic colorectal surgery, in order to identify patients who
      could benefit from alternatives to allogenic PBT such as erythropoietin
      administration, autologous blood transfusion, and possibly preoperative blood
      transfusion. METHODS: Five hundred patients who underwent laparoscopic colorectal
      surgery between the years 2003 and 2011 were reviewed. Patient demographics and
      clinicopathologic variables were collected prospectively. Other clinical data
      were collected directly from the computerized records of the in-hospital blood
      bank. PBT was defined as transfusion of allogenic red blood cells during the day
      of operation or within the postoperative hospitalization. The associations
      between PBT and patient variables were assessed by univariate and multivariate
      analyses. RESULTS: Of the 500 patients, 134 patients (26.8 %) received PBT.
      Multivariate analysis revealed four preoperative variables as significant risk
      factors for PBT: preoperative hemoglobin (P = 0.001), lower rectal surgery (P =
      0.009), Charlson comorbidity score (P = 0.001), and malignancy (P = 0.024).
      CONCLUSIONS: Preoperative Charlson score, hemoglobin level, carcinoma, and lower
      rectum pathologies were found to be independent risk factors for PBT in patients
      undergoing laparoscopic colorectal surgery. Evaluation of these risk factors
      prior to surgery may be helpful in selecting the patients who could benefit from
      possible alternatives to perioperative allogeneic blood transfusion and help
      constitute guidelines for a more responsible use of these alternatives.

PMID- 24736987
TI  - Timing of infectious complications following breast-conserving therapy with
      catheter-based accelerated partial breast irradiation.
AB  - BACKGROUND: Accelerated partial breast irradiation (APBI) has been used as an
      alternative to whole-breast irradiation as part of breast-conserving therapy.
      Indications and outcomes are topics of ongoing investigation. Previous
      publications have focused on early postoperative infections and reported low
      rates of delayed infection. We investigated the pattern of infection after
      catheter-based APBI at our institution. METHODS: Patients who underwent single
      entry catheter-based APBI were identified from an institutional prospective
      registry including data regarding comorbidities and outcomes. Time of infection
      was calculated from the date of definitive catheter insertion and classified as
      early (<=30 days) or delayed. RESULTS: A total of 91 breast cancer patients were
      treated with APBI and enrolled in the registry from 2009 to 2011. The median
      follow-up was 484 days. Breast infection occurred in 13 (14.3 %), with 3 (3.3 %)
      occurring within 30 days of catheter placement and 10 (11.0 %) in a delayed
      fashion. Four patients required hospital admission, five underwent percutaneous
      aspiration, and one underwent incision and drainage. Eight were treated as
      outpatients with oral antibiotics alone. CONCLUSIONS: Consistent with other
      reports, we found an overall infection rate of 14.3 % with single-entry catheter
      based APBI. There were substantially fewer infections in the early postoperative
      period than reported elsewhere, but there were more delayed infections. The
      intensive follow-up in our study likely identified late infections that may not
      have otherwise been recognized. Vigilance for infectious complications must
      continue beyond the immediate treatment period in patients undergoing catheter
      based APBI. These infections can range in severity but typically can be managed
      in an outpatient setting.

PMID- 24736988
TI  - Modified open-door laminoplasty for the surgical treatment of cervical
      spondylotic myelopathy in elderly patients.
AB  - BACKGROUND: The authors describe their experience with a modified version of the
      standard technique of open-door laminoplasty for the surgical treatment of
      spondylotic myelopathy in elderly patients with temporary removal of the laminae,
      extensive decompression, and pre-plating of the laminae beyond the surgical
      field. METHODS: Description of surgical anatomy, surgical technique, indications,
      limitations, complications, and specific perioperative considerations, as well as
      specific information to give to the patient about surgery and potential risks. A
      summary of ten key points is given. CONCLUSIONS: Transection of the laminae on
      both sides (temporary laminectomy) and pre-plating of the laminae outside of the
      surgical field has several advantages: better decompression of the spinal canal
      and the neuroforamina on both sides, easier undercutting of adjacent vertebral
      arches for cranio-caudal decompression, and no risk of spinal cord injury by the
      screwdriver when attaching plates to the laminae.

PMID- 24736990
TI  - Author response to: hypoxia a consequence of obesity and also a tool to treat
      excessive weight loss.

PMID- 24736991
TI  - Baicalein increases the cytotoxicity of cisplatin by enhancing gap junction
      intercellular communication.
AB  - Drug resistance limits the clinical application of cisplatin, a widely used
      chemotherapeutic agent. Gap junction (GJ) is a channel that enhances cytotoxicity
      of certain chemotherapeutic agents. Baicalein is well known for its antitumor
      activity. This study investigated the effect of baicalein on cisplatin
      cytotoxicity and the relationship between this effect and the modulation of the
      GJ function in connexin 26 (Cx26)-transfected HeLa cells. The sulforhodamine B
      (SRB) assay was used to examine the effect of baicalein on cell viability. A
      'parachute' assay was used to investigate the effect of baicalein on GJ function.
      The effects of baicalein on cisplatin cytotoxicity and GJ function were assayed
      by standard colony-forming assays. The expression of Cx26 was monitored by
      western blotting. It was observed that exposure of Cx26-transfected cells to
      cisplatin reduced the number of colonies formed in low-density cultures (no GJ
      formation) and in high-density cultures (GJ formation), but the toxic effect was
      greater when cells were seeded at a high density. In the absence of connexin
      expression or with blockage of connexin channels however, cell density had no
      effect on cisplatin toxicity. Baicalein significantly enhanced cisplatin
      cytotoxicity, but this effect required the presence of functional GJs between the
      cells. In conclusion, the dependence of cisplatin toxicity on cell density is
      mediated by GJs. Baicalein increases cisplatin cytotoxicity through enhancing GJ
      intercellular communication. 

PMID- 24736992
TI  - Transgenic crops: the present state and new ways of genetic modification.
AB  - Transgenic crops were first commercialised almost 20 years ago, which makes it a
      good opportunity to reflect on this technology. In this review, we compare its
      status with the predictions included in Vasil's forecast published in 2002. Our
      analysis shows that science has provided a wide range of possibilities to modify
      different traits in plants, yet the economy benefits from that range to very
      different extents. We also point out the most important constituents of the
      technology development involving methodology improvement and novel traits
      expressed in varieties introduced into agriculture. Using native genes (or their
      elements) in transgenes, accumulating previously produced transgenes to cascade
      resistance and using herbicide resistance as a selectable marker have been
      considered typical of novel genetically modified (GM) plant varieties. A vast
      portion of the novelties in stacked varieties is doubtful in terms of EU
      regulations. Attention has also been directed to completely novel methodology
      solutions that hold out the prospect of a more comprehensive use of genetic
      modification in agriculture as a whole, and, particularly, make its use possible
      in the EU and even in sustainable agriculture. 

PMID- 24736994
TI  - Self-assembled surfactants on patterned surfaces: confinement and cooperative
      effects on aggregate morphology.
AB  - The adsorption and self-assembly of surfactants are ubiquitous processes in
      several technological applications, including the manufacture of nano-structured
      materials using bottom-up strategies. Although much is known about the adsorption
      of surfactants on homogeneous flat surfaces from experiments, theory, and
      simulations, limited information is available, in quantifiable terms, regarding
      the adsorption of surfactants on surfaces with chemical and/or morphological
      heterogeneity. In an effort to fill this knowledge gap, we report here results
      obtained using equilibrium dissipative particle dynamics (DPD) simulations for
      the adsorption of model surfactants onto patterned flat surfaces (i.e., flat
      surfaces with chemical heterogeneity). The patterns consist of one or two stripes
      of variable width on which the surfactants could adsorb. The adsorbing stripes
      are surrounded by a surface that effectively repels the surfactants. This
      repelling surface, perhaps not realistic, allows us to quantify the effect of
      lateral confinement on the morphology of surfactant aggregates. When the stripe
      width is large (effectively providing a homogeneous flat surface), the
      surfactants yield a flat monolayer. Our simulations suggest that the flat
      monolayers become hemi-cylinders, hemi-spheres, and individual surfactants as the
      stripe width decreases, a consequence of lateral confinement. In some cases our
      simulations show evidence of cooperative effects when two adsorbing stripes are
      present on the surface. If the distance between the stripes and the widths of the
      stripes are both less than about one surfactant length, hemi-cylindrical shells
      and irregular structures are observed because of cooperativity; otherwise the
      results match those found for a single isolated stripe. Our predictions could be
      useful for the design of new nano-structured materials and coatings, for
      applications ranging from nano-fluidic devices to nano-reactors. 

PMID- 24736995
TI  - Genetics in PSC: what do the "risk genes" teach us?
AB  - A role of genetics in primary sclerosing cholangitis (PSC) development is now
      firmly established. A total of 16 risk genes have been reported at highly robust
      ("genome-wide") significance levels, and ongoing efforts suggest that the list
      will ultimately be considerably longer. Importantly, this genetic risk pool so
      far accounts for less than 10 % of an estimated overall PSC susceptibility. The
      relative importance of genetic versus environmental factors (including gene-gene
      and gene-environment interactions) in remaining aspects of PSC pathogenesis is
      unknown, and other study designs than genome-wide association studies are needed
      to explore these aspects. For some of the loci, e.g. HLA and FUT2, distinct
      interacting environmental factors may exist, and working from the genetic
      associations may prove one valid path for determining the specific nature of
      environmental triggers. So far the biological implications for PSC risk genes are
      typically merely hypothesized based on previously published literature, and there
      is therefore a strong need for dedicated translational studies to determine their
      roles within the specific disease context of PSC. Apparently, most risk loci seem
      to involve in a subset of biological pathways for which genetic associations
      exist in a multitude of immune-mediated diseases, accounting for both
      inflammatory bowel disease as well as prototypical autoimmunity. In the present
      article, we will survey the current knowledge on PSC genetics with a particular
      emphasis on the pathophysiological insight potentially gained from genetic risk
      loci involving in this profound immunogenetic pleiotropy.

PMID- 24736996
TI  - Crucial Role of Viral Reactivation in the Development of Severe Drug Eruptions: a
      Comprehensive Review.
AB  - A growing number of cells, mediators, and pathways have been implicated in severe
      drug eruptions. Fifteen years ago, we published landmark studies that sparked the
      current advances in our understanding of the role of viral reactivations in
      severe drug eruptions. Viral reactivations then became critically important as
      diagnostic tools, but how precisely they participated in the pathogenesis
      remained less well-defined. The question of whether viral reactivations are
      pathogenic or are instead as epiphenomenon of severe tissue damage has plagued
      the field of drug allergy for some decades. Recent evidence points to a crucial
      role for tissue-resident memory T (TRM) cells in immune protection against viral
      infections. Yet immune protection against viral infections is but one side of a
      coin, the other side of which comprises effector cells capable of mediating
      severe immunopathology: Once drug antigen is cross-recognized by these T cells,
      they could be activated to kill surrounding epidermal cells, resulting in drug
      induced tissue damage. Such TRM cells could persistently reside in the skin
      lesions of fixed drug eruptions (FDE) and are most likely a major cell type
      responsible for the development of FDE. We also discuss the role of regulatory T
      (Treg) cells in the setting of drug allergy, in which herpesviruses are
      reactivated in sequence. Although many details of the complicated interactions
      among viruses, anti-viral immune responses, TRM cells, and Treg cells remain to
      be elucidated, we review the current status of this rapidly advancing field.

PMID- 24736997
TI  - A novel protein, CHRONO, functions as a core component of the mammalian circadian
      clock.
AB  - Circadian rhythms are controlled by a system of negative and positive genetic
      feedback loops composed of clock genes. Although many genes have been implicated
      in these feedback loops, it is unclear whether our current list of clock genes is
      exhaustive. We have recently identified Chrono as a robustly cycling transcript
      through genome-wide profiling of BMAL1 binding on the E-box. Here, we explore the
      role of Chrono in cellular timekeeping. Remarkably, endogenous CHRONO occupancy
      around E-boxes shows a circadian oscillation antiphasic to BMAL1. Overexpression
      of Chrono leads to suppression of BMAL1-CLOCK activity in a histone deacetylase
      (HDAC) -dependent manner. In vivo loss-of-function studies of Chrono including
      Avp neuron-specific knockout (KO) mice display a longer circadian period of
      locomotor activity. Chrono KO also alters the expression of core clock genes and
      impairs the response of the circadian clock to stress. CHRONO forms a complex
      with the glucocorticoid receptor and mediates glucocorticoid response. Our
      comprehensive study spotlights a previously unrecognized clock component of an
      unsuspected negative circadian feedback loop that is independent of another
      negative regulator, Cry2, and that integrates behavioral stress and epigenetic
      control for efficient metabolic integration of the clock. 

PMID- 24736998
TI  - Spectroscopic investigations of the interaction of the anti-hypertension drug
      valsartan with human serum albumin.
AB  - The aim of the present study was to investigate the interaction between
      valsartan, an anti-hypertension drug, and human serum albumin (HSA) using
      spectroscopic techniques, including fluorescence, ultraviolet-visible absorption,
      synchronous fluorescence and circular dichroism (CD). The results demonstrated
      that valsartan and HSA form a complex and that a static quenching mechanism
      occurs. In addition, the binding constant and the number of binding sites for
      valsartan on HSA were analyzed. Hydrophobic interactions and hydrogen bonds were
      the predominant forces in the association reaction based on thermodynamic
      parameters. The distance between the donor (HSA) and the acceptor (valsartan) was
      1.994 nm as derived from Forster's theory. Alterations in the secondary structure
      of HSA in the presence of valsartan were assessed using synchronous fluorescence
      and CD. This study provides an enhanced understanding of the pharmacodynamic
      effects of valsartan on the physiologically important protein HSA.

PMID- 24736999
TI  - Somatostatin analog withdrawal in patients with acromegaly: an elusive goal?

PMID- 24737001
TI  - Nationwide radiation dose survey of computed tomography for fetal skeletal
      dysplasias.
AB  - BACKGROUND: Recently, computed tomography (CT) has been used to diagnose fetal
      skeletal dysplasia. However, no surveys have been conducted to determine the
      radiation exposure dose and the diagnostic reference level (DRL). OBJECTIVE: To
      collect CT dose index volume (CTDIvol) and dose length product (DLP) data from
      domestic hospitals implementing fetal skeletal 3-D CT and to establish DRLs for
      Japan. MATERIALS AND METHODS: Scan data of 125 cases of 20 protocols from 16
      hospitals were analyzed. The minimum, first-quartile, median, third-quartile and
      maximum values of CTDIvol and DLP were determined. The time-dependent change in
      radiation dose setting in hospitals with three or more cases with scans was also
      examined. RESULTS: The minimum, first-quartile, median, third-quartile and
      maximum CTDIvol values were 2.1, 3.7, 7.7, 11.3 and 23.1 mGy, respectively, and
      these values for DLP were 69.0, 122.3, 276.8, 382.6 and 1025.6 mGy.cm,
      respectively. Six of the 12 institutions reduced the dose setting during the
      implementation period. CONCLUSIONS: The DRLs of CTDIvol and DLP for fetal CT were
      11.3 mGy and 382.6 mGy.cm, respectively. Institutions implementing fetal CT
      should use these established DRLs as the standard and make an effort to reduce
      radiation exposure by voluntarily decreasing the dose.

PMID- 24737002
TI  - Insight into the growth dynamics and systematic affinities of the Late Cretaceous
      Gargantuavis from bone microstructure.
AB  - Enigmatic avialan remains of Gargantuavis philoinos from the Ibero-Armorican
      island of the Late Cretaceous European archipelago (Southern France) led to a
      debate concerning its taxonomic affinities. Here, we show that the bone
      microstructure of Gargantuavis resembles that of Apteryx, the extinct emeids and
      Megalapteryx from New Zealand, and indicates that like these slow-growing
      terrestrial birds, it took several years to attain skeletal maturity. Our
      findings suggest that the protracted cyclical growth in these ornithurines may
      have been in response to insular evolution.

PMID- 24737000
TI  - Machine learning helps identify CHRONO as a circadian clock component.
AB  - Over the last decades, researchers have characterized a set of "clock genes" that
      drive daily rhythms in physiology and behavior. This arduous work has yielded
      results with far-reaching consequences in metabolic, psychiatric, and neoplastic
      disorders. Recent attempts to expand our understanding of circadian regulation
      have moved beyond the mutagenesis screens that identified the first clock
      components, employing higher throughput genomic and proteomic techniques. In
      order to further accelerate clock gene discovery, we utilized a computer-assisted
      approach to identify and prioritize candidate clock components. We used a simple
      form of probabilistic machine learning to integrate biologically relevant, genome
      scale data and ranked genes on their similarity to known clock components. We
      then used a secondary experimental screen to characterize the top candidates. We
      found that several physically interact with known clock components in a mammalian
      two-hybrid screen and modulate in vitro cellular rhythms in an immortalized mouse
      fibroblast line (NIH 3T3). One candidate, Gene Model 129, interacts with BMAL1
      and functionally represses the key driver of molecular rhythms, the BMAL1/CLOCK
      transcriptional complex. Given these results, we have renamed the gene CHRONO
      (computationally highlighted repressor of the network oscillator). Bi-molecular
      fluorescence complementation and co-immunoprecipitation demonstrate that CHRONO
      represses by abrogating the binding of BMAL1 to its transcriptional co-activator
      CBP. Most importantly, CHRONO knockout mice display a prolonged free-running
      circadian period similar to, or more drastic than, six other clock components. We
      conclude that CHRONO is a functional clock component providing a new layer of
      control on circadian molecular dynamics. 

PMID- 24737003
TI  - Is the ability to integrate parts into wholes affected in autism spectrum
      disorder?
AB  - There is considerable debate about whether people with autism spectrum disorder
      (ASD) are biased toward local information and whether this disrupts their ability
      to integrate two complex shapes elements into a single figure. Moreover, few have
      examined the relationship between integration ability and ASD symptom severity.
      Adolescent/adult males with ASD and age and IQ-matched controls were compared on
      their performance of a simple silhouette-to-shape matching task and a higher
      order shape-integration task. Relative to basic silhouette-to-shape matching, ASD
      participants were disproportionately slower than controls on shape-integration.
      Moreover, this relative slowing correlated with increased symptom severity in ASD
      participants. These findings support the notion that integrating local
      information is disproportionately more challenging in ASD; this weakness may play
      a role in ASD symptomatology. 

PMID- 24737004
TI  - Study of flexible fin and compliant joint stiffness on propulsive performance:
      theory and experiments.
AB  - The caudal fin is a major source of thrust generation in fish locomotion. Along
      with the fin stiffness, the stiffness of the joint connecting the fish body to
      the tail plays a major role in the generation of thrust. This paper investigates
      the combined effect of fin and joint flexibility on propulsive performance using
      theoretical and experimental studies. For this study, fluid-structure interaction
      of the fin has been modeled using the 2D unsteady panel method coupled with
      nonlinear Euler-Bernoulli beam theory. The compliant joint has been modeled as a
      torsional spring at the leading edge of the fin. A comparison of self-propelled
      speed and efficiency with parameters such as heaving and pitching amplitude,
      oscillation frequency, flexibility of the fin and the compliant joint is
      reported. The model also predicts the optimized stiffnesses of the compliant
      joint and the fin for maximum efficiency. Experiments have been carried out to
      determine the effect of fin and joint stiffness on propulsive performance.
      Digital image correlation has been used to measure the deformation of the fins
      and the measured deformation is coupled with the hydrodynamic model to predict
      the performance. The predicted theoretical performance behavior closely matches
      the experimental values. 

PMID- 24737005
TI  - A novel begomovirus isolated from sida contains putative cis- and trans-acting
      replication specificity determinants that have evolved independently in several
      geographical lineages.
AB  - A novel begomovirus isolated from a Sida rhombifolia plant collected in Sinaloa,
      Mexico, was characterized. The genomic components of sida mosaic Sinaloa virus
      (SiMSinV) shared highest sequence identity with DNA-A and DNA-B components of
      chino del tomate virus (CdTV), suggesting a vertical evolutionary relationship
      between these viruses. However, recombination analysis indicated that a short
      segment of SiMSinV DNA-A encompassing the plus-strand replication origin and the
      5'-proximal 43 codons of the Rep gene was derived from tomato mottle Taino virus
      (ToMoTV). Accordingly, the putative cis- and trans-acting replication specificity
      determinants of SiMSinV were identical to those of ToMoTV but differed from those
      of CdTV. Modeling of the SiMSinV and CdTV Rep proteins revealed significant
      differences in the region comprising the small beta1/beta5 sheet element, where
      five putative DNA-binding specificity determinants (SPDs) of Rep (i.e., amino
      acid residues 5, 8, 10, 69 and 71) were previously identified. Computer-assisted
      searches of public databases led to identification of 33 begomoviruses from three
      continents encoding proteins with SPDs identical to those of the Rep encoded by
      SiMSinV. Sequence analysis of the replication origins demonstrated that all 33
      begomoviruses harbor potential Rep-binding sites identical to those of SiMSinV.
      These data support the hypothesis that the Rep beta1/beta5 sheet region
      determines specificity of this protein for DNA replication origin sequences. 

PMID- 24737006
TI  - Analysis of the complete genome of a virus associated with twisted leaf disease
      of cherry reveals evidence of a close relationship to unassigned viruses in the
      family Betaflexiviridae.
AB  - The genome of a virus associated with cherry twisted leaf disease (CTLaV, isolate
      ZH) was sequenced and consists of 8431 nucleotides, excluding a poly(A) tail at
      the 3' end. Genome analysis shows that CTLaV-ZH represents a new and distinct
      species and has a genome organization similar to those of unassigned viruses in
      the family Betaflexiviridae. The CTLaV-ZH genome has five open reading frames
      (ORFs), with putative ORFs within ORF2 and ORF5, identified as ORF2a and ORF5a,
      respectively. The AUG start codons of ORF2a and ORF5a are in contexts suitable
      for efficient translation, with appropriate stop codons in frame. 

PMID- 24737007
TI  - Measuring relational and intrapersonal empowerment: testing instrument validity
      in a former soviet country with a secular muslim culture.
AB  - Research and evaluation studies measuring the construct of empowerment within
      international community development and human rights initiatives are rare due to
      a lack of validated measures appropriate for the cultural context. This study
      represents an initial effort to develop and test the Brief Azerbaijani
      Empowerment Scale (BAES), an instrument designed to assess relational and
      intrapersonal components of psychological empowerment among adult community
      residents (n = 350) in Azerbaijan, a former Soviet country with a predominantly
      Muslim culture. Exploratory factor analysis was used to examine the underlying
      dimensionality of the BAES, and path analysis was used to examine relationships
      between subscales of the BAES and a set of conceptually relevant variables (i.e.,
      alienation, sense of community, and involvement in community organizations).
      Findings supported the reliability and validity of the BAES, which may be useful
      to future efforts to develop more comprehensive measures of intrapersonal and
      relational empowerment. Implications for future research and practice are
      discussed.

PMID- 24737008
TI  - Fuzheng Qingjie recipe induces apoptosis in HepG2 cells via P38 MAPK activation
      and the mitochondria-dependent apoptotic pathway.
AB  - Fuzheng Qingjie (FZQJ) recipe is a polyherbal Chinese medicine capable of
      suppressing tumor growth and is used as an adjuvant therapy for various types of
      cancer. However, its anticancer mechanisms are yet to be fully elucidated. In the
      present study, we explored whether p38 mitogen-activated protein kinase (MAPK)
      was involved in FZQJ-mediated mitochondria-dependent apoptosis in human
      hepatocellular carcinoma cells. 3-(4,5-Dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide (MTT) assays were used to measure the viability of
      HepG2 cells. 4,6-Diamidino-2-phenylindole (DAPI) and Annexin-V fluorescein
      isothiocyanate (FITC) were used to analyze the apoptosis of HepG2 cells. The
      mitochondrial membrane potential (?psi) and phosphorylated P38 MAPK protein were
      examined by a flow cytometer following 5,5',6,6'-tetrachloro-1,1',3,3'
      tetraethylbenzimidazolcarbocyanine iodide (JC-1) and Alexa Fluor(r) 647 mouse
      anti-phosphorylated P38 MAPK antibody staining, respectively. The activation of
      caspase-9 and caspase-3 were measured using colorimetric assays. Additionally,
      Bcl-2 and Bax expression were examined using reverse transcription polymerase
      chain reaction (RT-PCR) and western blot analysis. The results demonstrated that
      water extract of FZQJ was able to induce apoptosis of HepG2 cells in vitro. FZQJ
      induced apoptosis was accompanied by the loss of ?psi, downregulation of Bcl-2
      and upregulation of Bax expression, and the activation of caspase-3, -9 and P38
      MAPK. These results indicated that FZQJ induced apoptosis in HepG2 cells at least
      via P38 MAPK activation and the mitochondria-dependent apoptotic pathway.

PMID- 24737009
TI  - Clinical significance of Wnt-11 and squamous cell carcinoma antigen expression in
      cervical cancer.
AB  - The purpose of the study was to determine the expression patterns of Wnt-11 and
      squamous cell carcinoma antigen in cervical cancer tissues and to explore their
      clinical significance and correlation with clinicopathological parameters. The
      expression of Wnt-11 and squamous cell carcinoma antigen was detected in 127
      cervical cancer tissues, 21 cervical intraepithelial neoplasia, as well as in 20
      healthy controls by immunohistochemistry, and the relationship of Wnt-11 and
      squamous cell carcinoma antigen expression with clinicopathological parameters
      was analyzed. Both Wnt-11 and squamous cell carcinoma antigen were more commonly
      expressed in cervical cancer than in cervical intraepithelial neoplasia and in
      normal cervical tissue (respectively; P < 0.05); further, Wnt-11 and squamous
      cell carcinoma antigen expression in cervical cancer were positively correlated
      (r = 0.271, P < 0.05). In comparing the expression with clinicopathological
      parameters of tumor samples, Wnt-11 and squamous cell carcinoma antigen were both
      associated with FIGO stage, lymph node metastasis, and tumor size (P < 0.05), but
      not with patient age, pathological type, or differentiation. Increased Wnt-11
      protein levels in cervical carcinoma samples were associated with a poor outcome
      in univariate and multivariate analysis. Wnt-11 and squamous cell carcinoma
      antigen are related to the malignancy degree and metastasis of cervical cancer,
      and thus may play a coordinating role in the occurrence and progression of
      cervical cancer. The study indicated that Wnt-11 may be a useful prognostic
      indicator for cervical carcinoma.

PMID- 24737011
TI  - Nanostructured weathering steel for matrix-free laser desorption ionisation mass
      spectrometry and imaging of metabolites, drugs and complex glycans.
AB  - Weathering steel has been employed for the first time to prepare sample plates
      for matrix-free laser desorption ionisation mass spectrometry (LDI-MS) of small
      molecules up to a mass range of around 1500 Da. The effective UV absorption, heat
      conductivity and porosity of the nanostructured inner rust layer formed during
      passivation determine the excellent performance in LDI-MS for a broad range of
      different analyte classes. The inexpensive material was evaluated in a series of
      relevant analytical applications ranging from the matrix-free detection of serum
      metabolites, lactose quantification, lipid analysis in milk to the glycoprofiling
      of antibodies and imaging mass spectrometry of brain tissue samples. 

PMID- 24737010
TI  - Low expression of claudin-4: an indicator of recurrence in esophageal squamous
      cell carcinoma after Ivor Lewis esophagectomy?
AB  - The high recurrence rate after surgery is the main reason for the poor prognosis
      of esophageal squamous cell carcinoma (ESCC) patients. Finding indicators of
      recurrence and taking adjuvant therapy may be useful for patients in high risk of
      recurrence. claudin-4 (CLDN4) is the core protein to form the tight junction,
      which plays an important role in cell adhesion, and its aberrant expression were
      detected in various cancers while its expression and functions in ESCC still
      remained unclear. Here, we detected the expression of CLDN4 in 114 ESCC tissue
      samples by real-time RT-PCR and immunohistochemistry, and the result showed that
      the low expression of CLDN4 correlated with a higher T staging (P = 0.010),
      lymphatic metastasis (P < 0.001) and recurrence status (P = 0.002). And the Cox
      regression analysis showed that the T classification (P = 0.005), lymph node
      metastasis (P = 0.003) and low CLDN4 expression (P = 0.029) were independent risk
      factors of recurrence. Further, we proved the CLDN4 in inhibiting growth, colony
      formation and invasion in vitro by establishing two stable CLDN4-silencing ESCC
      cell lines. In conclusion, CLDN4 played an important role in preventing
      metastasis and could be an effective biomarker to predict the recurrence of ESCC.

PMID- 24737014
TI  - Remote-controlled magnetic navigation and ablation of atrial flutter in a patient
      with an extracardiac total cavopulmonary connection.

PMID- 24737013
TI  - The longitudinal and interactive effects of HIV status, stimulant use, and host
      genotype upon neurocognitive functioning.
AB  - Both human immunodeficiency virus (HIV)-1 infection and illicit stimulant use can
      adversely impact neurocognitive functioning, and these effects can be additive.
      However, significant variability exists such that as-of-yet unidentified
      exogenous and endogenous factors affect one's risk for neurocognitive impairment.
      Literature on both HIV and stimulant use indicates that host genetic variants in
      immunologic and dopamine-related genes are one such factor. In this study, the
      individual and interactive effects of HIV status, stimulant use, and genotype
      upon neurocognitive functioning were examined longitudinally over a 10-year
      period. Nine hundred fifty-two Caucasian HIV+ and HIV- cases from the Multicenter
      AIDS Cohort Study were included. All cases had at least two comprehensive
      neurocognitive evaluations between 1985 and 1995. Pre-highly active
      antiretroviral therapy (HAART) data were examined in order to avoid the
      confounding effect of variable drug regimens. Linear mixed models were used, with
      neurocognitive domain scores as the outcome variables. No four-way interactions
      were found, indicating that HIV and stimulant use do not interact over time to
      affect neurocognitive functioning as a function of genotype. Multiple three-way
      interactions were found that involved genotype and HIV status. All
      immunologically related genes found to interact with HIV status affected
      neurocognitive functioning in the expected direction; however, only C-C chemokine
      ligand 2 (CCL2) and CCL3 affected HIV+ individuals specifically. Dopamine-related
      genetic variants generally affected HIV-negative individuals only. Neurocognitive
      functioning among HIV+ individuals who also used stimulants was not significantly
      different from those who did not use stimulants. The findings support the role of
      immunologically related genetic differences in CCL2 and CCL3 in neurocognitive
      functioning among HIV+ individuals; however, their impact is minor. Being
      consistent with findings from another cohort, dopamine (DA)-related genetic
      differences do not appear to impact the longitudinal neurocognitive functioning
      of HIV+ individuals. 

PMID- 24737015
TI  - Where can cone penetrometer technology be applied? Development of a map of Europe
      regarding the soil penetrability.
AB  - Over the past decades, significant efforts have been invested in the development
      of push-in technology for site characterization and monitoring for geotechnical
      and environmental purposes and have especially been undertaken in the Netherlands
      and Germany. These technologies provide the opportunity for faster, cheaper, and
      collection of more reliable subsurface data. However, to maximize the technology
      both from a development and implementation point of view, it is necessary to have
      an overview of the areas suitable for the application of this type of technology.
      Such an overview is missing and cannot simply be read from existing maps and
      material. This paper describes the development of a map showing the feasibility
      or applicability of Direct Push/Cone Penetrometer Technology (DPT/CPT) in Europe
      which depends on the subsurface and its extremely varying properties throughout
      Europe. Subsurface penetrability is dependent on a range of factors that have not
      been mapped directly or can easily be inferred from existing databases,
      especially the maximum depth reachable would be of interest. Among others, it
      mainly depends on the geology, the soil mechanical properties, the type of
      equipment used as well as soil-forming processes. This study starts by looking at
      different geological databases available at the European scale. Next, a scheme
      has been developed linking geological properties mapped to geotechnical
      properties to determine basic penetrability categories. From this, a map of soil
      penetrability is developed and presented. Validating the output by performing
      field tests was beyond the scope of this study, but for the country of the
      Netherlands, this map has been compared against a database containing actual cone
      penetrometer depth data to look for possible contradictory results that would
      negate the approach. The map for the largest part of Europe clearly shows that
      there is a much wider potential for the application of Direct Push Technology
      than is currently seen. The study also shows that there is a lack of large-scale
      databases that contain depth-resolved data as well as soil mechanical and
      physical properties that can be used for engineering purposes in relation to the
      subsurface. 

PMID- 24737016
TI  - Performance evaluation of different solar advanced oxidation processes applied to
      the treatment of a real textile dyeing wastewater.
AB  - The performance of different solar-driven advanced oxidation processes (AOPs),
      such as TiO2/UV, TiO2/H2O2/UV, and Fe(2+)/H2O2/UV-visible in the treatment of a
      real textile effluent using a pilot plant with compound parabolic collectors
      (CPCs), was investigated. The influence of the main photo-Fenton reaction
      variables such as iron concentration (20-100 mg Fe(2+) L(-1)), pH (2.4-4.5),
      temperature (10-50  degrees C), and irradiance (22-68 WUV m(-2)) was evaluated in
      a lab-scale prototype using artificial solar radiation. The real textile
      wastewater presented a beige color, with a maximum absorbance peak at 641 nm,
      alkaline pH (8.1), moderate organic content (dissolved organic carbon (DOC) = 129
      mg C L(-1) and chemical oxygen demand (COD) = 496 mg O2 L(-1)), and high
      conductivity mainly associated to the high concentration of chloride (1.1 g Cl(-)
      L(-1)), sulfate (0.4 g SO 4 (2 -) L(- 1)), and sodium (1.2 g Na(+) L(-1)) ions.
      Although all the processes tested contributed to complete decolorization and
      effective mineralization, the most efficient process was the solar photo-Fenton
      with an optimum catalyst concentration of 60 mg Fe(2+) L(-1), leading to 70 %
      mineralization (DOCfinal = 41 mg C L(-1); CODfinal < 150 mg O2 L(-1)) at pH 3.6,
      requiring a UV energy dose of 3.5 kJUV L(-1) (t 30 W = 22.4 min; [Formula: see
      text]; [Formula: see text]) and consuming 18.5 mM of H2O2.

PMID- 24737017
TI  - Electrochemical incineration of indigo. A comparative study between 2D (plate)
      and 3D (mesh) BDD anodes fitted into a filter-press reactor.
AB  - This paper compares the performance of 2D (plate) and 3D (mesh) boron-doped
      diamond (BDD) electrodes, fitted into a filter-press reactor, during the
      electrochemical incineration of indigo textile dye as a model organic compound in
      chloride medium. The electrolyses were carried out in the FM01-LC reactor at mean
      fluid velocities between 0.9 <= u <= 10.4 and 1.2 <= u <= 13.9 cm s(-1) for the
      2D BDD and the 3D BDD electrodes, respectively, at current densities of 5.63 and
      15 mA cm(-2). The oxidation of the organic matter was promoted, on the one hand,
      via the physisorbed hydroxyl radicals (BDD(.OH)) formed from water oxidation at
      the BDD surface and, on the other hand, via active chlorine formed from the
      oxidation of chloride ions on BDD. The performance of 2D BDD and 3D BDD
      electrodes in terms of current efficiency, energy consumption, and charge passage
      during the treatments is discussed.

PMID- 24737018
TI  - Variability of SO2, CO, and light hydrocarbons over a megacity in Eastern India:
      effects of emissions and transport.
AB  - The Indo-Gangetic plain (IGP) has received extensive attention of the global
      scientific community due to higher levels of trace gases and aerosols over this
      region. Satellite retrievals and model simulations show that, in particular, the
      eastern part IGP is highly polluted. Despite this attention, in situ measurements
      of trace gases are very limited over this region. This paper presents
      measurements of SO2, CO, CH4, and C2-C5 NMHCs during March 2012-February 2013
      over Kolkata, a megacity in the eastern IGP, with a focus on processes impacting
      their levels. The mean SO2 and C2H6 concentrations during winter and post-monsoon
      periods were eight and three times higher compared to pre-monsoon and monsoon.
      Early morning enhancements in SO2 and several NMHCs during winter connote
      boundary layer effects. Daytime elevations in SO2 during pre-monsoon and monsoon
      suggest impacts of photo-oxidation. Inter-species correlations and trajectory
      analysis evince transport of SO2 from regional combustion sources (e.g., coal
      burning in power plants, industries) along the east of the Indo-Gangetic plain
      impacting SO2 levels at the site. However, C2H2 to CO ratio over Kolkata, which
      are comparable to other urban regions in India, show impacts of local biofuel
      combustions. Further, high levels of C3H8 and C4H10 evince the dominance of
      LPG/petrochemicals over the study location. The suite of trace gases measured
      during this study helps to decipher between impacts of local emissions and
      influence of transport on their levels.

PMID- 24737019
TI  - Evaluating the degradation of the herbicides picloram and 2,4-D in a
      compartmentalized reactive biobarrier with internal liquid recirculation.
AB  - Tordon is a widely used herbicide formulation of 2,4-dichlorophenoxyacetic acid
      (2,4-D) and 4-amino-3,5,6-trichloropicolinic acid (picloram), and it is
      considered a toxic herbicide. The purposes of this work were to assess the
      feasibility of a microbial consortium inoculated in a lab-scale compartmentalized
      biobarrier, to remove these herbicides, and isolate, identify, and evaluate their
      predominant microbial constituents. Volumetric loading rates of herbicides
      ranging from 31.2 to 143.9 g m(-3) day(-1), for 2,4-D, and 12.8 to 59.3 g m(-3)
      day(-1) for picloram were probed; however, the top operational limit of the
      biobarrier, detected by a decay in the removal efficiency, was not reached. At
      the highest loading rates probed, high average removal efficiencies of 2,4-D,
      99.56 +/- 0.44; picloram, 94.58 +/- 2.62; and chemical oxygen demand (COD), 89.42
      +/- 3.68, were obtained. It was found that the lab-scale biofilm reactor
      efficiently removed both herbicides at dilution rates ranging from 0.92 to 4.23
      day(-1), corresponding to hydraulic retention times from 1.087 to 0.236 days. On
      the other hand, few microbial strains able to degrade picloram are reported in
      the literature. In this work, three of the nine bacterial strains isolated
      cometabolically degrade picloram. They were identified as Hydrocarboniphaga sp.,
      Tsukamurella sp., and Cupriavidus sp.

PMID- 24737020
TI  - Arsenic-tolerant plant-growth-promoting bacteria isolated from arsenic-polluted
      soils in South Korea.
AB  - The Janghang smelter in Chungnam, South Korea started in 1936 was subsequently
      shutdown in 1989 due to heavy metal (loid) pollution concerns in the vicinity.
      Thus, there is a need for the soil in the area to be remediated to make it usable
      again especially for agricultural purposes. The present study was conducted to
      exploit the potential of arsenic (As)-tolerant bacteria thriving in the vicinity
      of the smelter-polluted soils to enhance phytoremediation of hazardous As. We
      studied the genetic and taxonomic diversity of 21 As-tolerant bacteria isolated
      from soils nearer to and away from the smelter. These isolates belonging to the
      genera Brevibacterium, Pseudomonas, Microbacterium, Rhodococcus, Rahnella, and
      Paenibacillus, could tolerate high concentrations of arsenite (As(III)) and
      arsenate (As(V)) with the minimum inhibitory concentration ranging from 3 to >20
      mM for NaAsO2 and 140 to 310 mM NaH2AsO4 . 7H2O, respectively. All isolates
      exhibited As(V) reduction except Pseudomonas koreensis JS123, which exhibited
      both oxidation and reduction of As. Moreover, all the 21 isolates produced indole
      acetic acid (IAA), 13 isolates exhibited 1-aminocyclopropane-1-carboxylic acid
      (ACC) deaminase activity, 12 produced siderophore, 17 solubilized phosphate, and
      13 were putative nitrogen fixers under in vitro conditions. Particularly,
      Rhodococcus aetherivorans JS2210, P. koreensis JS2214, and Pseudomonas sp. JS238
      consistently increased root length of maize in the presence of 100 and 200 MUM
      As(V). Possible utilization of these As-tolerant plant-growth-promoting bacteria
      can be a potential strategy in increasing the efficiency of phytoremediation in
      As-polluted soils. 

PMID- 24737021
TI  - An estimation of mercury concentrations in the local atmosphere of Almaden
      (Ciudad Real Province, South Central Spain) during the twentieth century.
AB  - We show the first estimations of long-term (100 years, 1900 to 2000) total
      gaseous mercury concentrations (TGM) in the urban area of Almaden. The estimation
      was carried out by comparing data on known metallic mercury production with
      measured TGM concentrations. The estimated diurnal background level ranges from
      60 to 120 ng m(-3) and corresponds to periods when the metallurgical complex
      (cinnabar roasting plant) was shut down. The average TGM concentration during the
      period from 1900 to 2000 was about 600 ng m(-3) (with peaks above 1,200 ng m(
      3)). Additionally, a 24-h-based TGM monitoring program has highlighted
      significant differences between the diurnal and nocturnal concentrations,
      particularly during the warmer months. In this regard, given that the average
      nocturnal to diurnal ratio is 2.12, we suggest that the average nocturnal
      concentrations must have exceeded 1,200 ng m(-3), and peak nocturnal
      concentrations could have reached levels up to 2,400 ng m(-3). Our estimations
      indicate that most parts of the town of Almaden were generally exposed to TGM
      concentrations in air that exceed the World Health Organization air quality
      guideline for Hg (1,000 ng m(-3)) for countryside and urban areas. 

PMID- 24737022
TI  - Dechlorane Plus and decabromodiphenyl ether in atmospheric particles of northeast
      Asian cities.
AB  - Atmospheric particles were collected in several cities in Japan (Sapporo,
      Sagamihara, Kanazawa, and Kitakyushu), Korea (Busan), and China (Beijing) using a
      high-volume air sampler equipped with a quartz fiber filter. The summer and
      winter samples were analyzed using gas chromatography-high-resolution mass
      spectrometry for Dechlorane Plus (DP). Decabromodiphenyl ether (BDE-209) was also
      analyzed for the samples from Kanazawa and Beijing. DP was detected in all
      samples. The mean total DP (SigmaDP) concentration was highest (6.7 pg/m(3)) and
      lowest (0.87 pg/m(3)) in the winter samples from Sagamihara and Busan,
      respectively. The seasonal variation of DP concentrations varied by sampling site
      in this study. BDE-209 was detected in all the analyzed samples except for one of
      the Kanazawa winter samples. BDE-209 concentration was considerably higher in
      Beijing than in Kanazawa. Significant correlations were found between the
      concentrations of SigmaDP and BDE-209 in the winter samples from Kanazawa and in
      both summer and winter samples from Beijing. This similarity in the atmospheric
      behavior of DP and BDE-209, especially in winter, is assumed to reflect a common
      end usage and release mechanism.

PMID- 24737023
TI  - Effect of Fenton treatment on the aquatic toxicity of bisphenol A in different
      water matrices.
AB  - Battery tests serve as integral tools to decide whether a treatment process is
      ecotoxicologically safe or not. In the present study, a battery of toxicity tests
      was employed to elucidate the toxicity of the potential endocrine-disrupting
      pollutant bisphenol A (BPA) and its advanced oxidation products. For this
      purpose, BPA was subjected to Fenton treatment in the growth medium of the test
      organisms employed as well as in real lake water. Treatment results indicated
      that BPA removals were fast and complete within less than a minute, whereas total
      organic carbon (TOC) removals were rather incomplete, speaking for the
      accumulation of refractory degradation products. The presence of chloride and/or
      natural organic matter influenced H2O2 consumption rates and the treatment
      performance of the Fenton's reagent as well. The sensitivity of the selected test
      organisms for BPA and its Fenton treatment products in different water matrices
      was found in the following decreasing order: the freshwater microalgae
      (Pseudokirchneriella subcapitata) > the freshwater cladoceran (Daphnia magna) >
      marine photobacteria (Vibrio fischeri).

PMID- 24737024
TI  - Landfill wall revegetation combined with leachate recirculation: a convenient
      procedure for management of closed landfills.
AB  - There is a need for a reliable sustainable option to effectively manage the
      landfill leachate generation. This study presents a simple procedure for the
      revegetation of the walls of closed landfills, employing the leachate as a
      fertirrigant. The native plants Lepidium sativum, Lactuca sativa, and Atriplex
      halimus, which suit the local climate, were chosen for this study in Southern
      Italy. The methodology was structured into three phases (i) early stage toxicity
      assessment phase (apical root length and germination tests), (ii) adult plant
      resistance assessment phase, and (iii) soil properties verification phase. The
      rationale of the proposed approach was first to look at the distinctive qualities
      and the potential toxicity in landfill leachates for fertigation purposes.
      Afterwards, through specific tests, the plants used were ranked in terms of
      resistance to the aqueous solution that contained leachate. Finally, after long
      term irrigation, any possible worsening of soil properties was evaluated. The
      results demonstrated the real possibility of using blended leachate as a
      fertigant for the revegetation of the walls of closed landfills. In particular,
      the plants maintained good health when leachate was blended at concentrations of
      lower than 25 and 5%, respectively for A. halimus and Lepidium sativum.
      Irrigation tests showed good resistance of the plants, even at dosages of 112 and
      133.5 mm m(-2), at maximum concentrations of 25 and 5%, respectively, for A.
      halimus and Lepidium sativum. The analysis of the total chlorophyll content and
      of aerial parts dried weight confirmed the results reported above.

PMID- 24737025
TI  - Bisphenol A exposure is not associated with area-level socioeconomic index in
      Australian children using pooled urine samples.
AB  - Bisphenol A (BPA) is used extensively in food-contact materials and has been
      detected routinely in populations worldwide; this exposure has been linked to a
      range of negative health outcomes in humans. There is some evidence of an
      association between BPA and different socioeconomic variables which may be the
      result of different dietary patterns. The aim of this study was to conduct a
      preliminary investigation of the association between BPA and socioeconomic status
      in Australian children using pooled urine specimens and an area-level
      socioeconomic index. Surplus pathology urine specimens collected from children
      aged 0-15 years in Queensland, Australia, as samples of convenience (n=469), were
      pooled by age, sex and area-level socioeconomic index (n=67 pools) and analysed
      for total BPA using online solid-phase extraction LC-MS/MS. Concentration ranged
      from 1.08 to 27.4 ng/ml with geometric mean 2.57 ng/ml, and geometric mean
      exposure was estimated as 70.3 ng/kg d(-1). Neither BPA concentration nor
      excretion was associated with age or sex, and the authors found no evidence of an
      association with socioeconomic status. These results suggest that BPA exposure is
      not associated with socioeconomic status in the Australian population due to
      relatively homogenous exposures in Australia, or that the socioeconomic gradient
      is relatively slight in Australia compared with other OECD countries.

PMID- 24737026
TI  - Geranylgeranylacetone blocks doxorubicin-induced cardiac toxicity and reduces
      cancer cell growth and invasion through RHO pathway inhibition.
AB  - Doxorubicin is a widely used chemotherapy for solid tumors and hematologic
      malignancies, but its use is limited due to cardiotoxicity. Geranylgeranylacetone
      (GGA), an antiulcer agent used in Japan for 30 years, has no significant adverse
      effects, and unexpectedly reduces ovarian cancer progression in mice. Because GGA
      reduces oxidative stress in brain and heart, we hypothesized that GGA would
      prevent oxidative stress of doxorubicin cardiac toxicity and improve
      doxorubicin's chemotherapeutic effects. Nude mice implanted with MDA-MB-231
      breast cancer cells were studied after chronic treatment with doxorubicin,
      doxorubicin/GGA, GGA, or saline. Transthoracic echocardiography was used to
      monitor systolic heart function and xenografts evaluated. Mice were euthanized
      and cardiac tissue evaluated for reactive oxygen species generation, TUNEL assay,
      and RHO/ROCK pathway analysis. Tumor metastases were evaluated in lung sections.
      In vitro studies using Boyden chambers were performed to evaluate GGA effects on
      RHO pathway activator lysophosphatidic acid (LPA)-induced motility and invasion.
      We found that GGA reduced doxorubicin cardiac toxicity, preserved cardiac
      function, prevented TUNEL-positive cardiac cell death, and reduced doxorubicin
      induced oxidant production in a nitric oxide synthase-dependent and independent
      manner. GGA also reduced heart doxorubicin-induced ROCK1 cleavage. Remarkably, in
      xenograft-implanted mice, combined GGA/doxorubicin treatment decreased tumor
      growth more effectively than doxorubicin treatment alone. As evidence of
      antitumor effect, GGA inhibited LPA-induced motility and invasion by MDA-MB-231
      cells. These anti-invasive effects of GGA were suppressed by geranylgeraniol
      suggesting GGA inhibits RHO pathway through blocking geranylation. Thus, GGA
      protects the heart from doxorubicin chemotherapy-induced injury and improves
      anticancer efficacy of doxorubicin in breast cancer.

PMID- 24737027
TI  - A small molecule that binds and inhibits the ETV1 transcription factor
      oncoprotein.
AB  - Members of the ETS transcription factor family have been implicated in several
      cancers, where they are often dysregulated by genomic derangement. ETS variant 1
      (ETV1) is an ETS factor gene that undergoes chromosomal translocation in prostate
      cancers and Ewing sarcomas, amplification in melanomas, and lineage dysregulation
      in gastrointestinal stromal tumors. Pharmacologic perturbation of ETV1 would be
      appealing in these cancers; however, oncogenic transcription factors are often
      deemed "undruggable" by conventional methods. Here, we used small-molecule
      microarray screens to identify and characterize drug-like compounds that modulate
      the biologic function of ETV1. We identified the 1,3,5-triazine small molecule
      BRD32048 as a top candidate ETV1 perturbagen. BRD32048 binds ETV1 directly,
      modulating both ETV1-mediated transcriptional activity and invasion of ETV1
      driven cancer cells. Moreover, BRD32048 inhibits p300-dependent acetylation of
      ETV1, thereby promoting its degradation. These results point to a new avenue for
      pharmacologic ETV1 inhibition and may inform a general means to discover small
      molecule perturbagens of transcription factor oncoproteins.

PMID- 24737028
TI  - Dual targeting of integrin alphavbeta3 and matrix metalloproteinase-2 for optical
      imaging of tumors and chemotherapeutic delivery.
AB  - Activatable cell-penetrating peptides (ACPP) provide a general strategy for
      molecular targeting by exploiting the extracellular protease activities
      associated with disease. Previous work used a matrix metalloproteinase (MMP-2 and
      9)-cleavable sequence in the ACPP to target contrast agents for tumor imaging and
      fluorescence-guided surgery. To improve specificity and sensitivity for MMP-2, an
      integrin alpha(v)beta(3)-binding domain, cyclic-RGD, was covalently linked to the
      ACPP. This co-targeting strategy relies on the interaction of MMP-2 with integrin
      alpha(v)beta(3), which are known to associate via the hemopexin domain of MMP-2.
      In U87MG glioblastoma cells in culture, dual targeting greatly improved ACPP
      uptake compared with either MMP or integrin alpha(v)beta(3) targeting alone. In
      vivo, dual-targeted ACPP treatment resulted in tumor contrast of 7.8 +/- 1.6, a
      10-fold higher tumor fluorescence compared with the negative control peptide, and
      increased probe penetration into the core of MDA-MB-231 tumors. This platform
      also significantly improved efficacy of the chemotherapeutic monomethylauristatin
      E (MMAE) in both MDA-MB-231 orthotopic human and syngeneic Py230 murine breast
      tumors. Treatment with cyclic-RGD-PLGC(Me)AG-MMAE-ACPP resulted in complete tumor
      regression in one quarter of MDA-MB-231 tumor-bearing mice, compared with no
      survival in the control groups. This rational mechanism for amplified delivery of
      imaging and potent chemotherapeutic agents avoids the use of antibodies and may
      be of considerable generality.

PMID- 24737029
TI  - DNA methylation status of a distinctively different subset of genes is associated
      with each histologic Lauren classification subtype in early gastric
      carcinogenesis.
AB  - DNA methylation change is known to play a crucial role in early gastric
      carcinogenesis. The present study aimed to identify and validate the correlation
      between differentially methylated regions (DMRs) and the subtypes of early
      gastric cancers (EGCs). Illumina Infinium methylation assay (IIMA; 450K BeadChip
      kit) was performed on fresh tumor and non-tumor tissues of 12 EGCs to screen the
      methylation status of 450,000 CpG sites. To evaluate the significance of DNA
      methylation in each histologic subtype, pyrosequencing assay (PA) was performed
      on 38 EGCs (18 intestinal-, 12 mixed- and 8 diffuse-type) using 12 genes selected
      from the screening. Between tumors of the intestinal-type (n=6), and diffuse-
      (n=4) plus mixed-types (n=2), 169 regions showed significant differences
      (intensity>3,000, Deltabeta>0.2) in IIMA. Hierarchical clustering using the 169
      DMRs revealed distinct separation between the two groups. In PA using 12 selected
      genes from the IIMA results, the aberrant methylation statuses of DVL2 (p=0.0186)
      and ETS1 (p=0.0222) were significantly related to diffuse- and mixed-types rather
      than the intestinal-type, while C19orf35 (p=0.019) and CNRIP1 (p=0.0473) were
      related to the diffuse-type rather than intestinal-type, and GAL3ST2 (p=0.0158)
      and ITGA3 (p=0.0273) were related to the mixed-type rather than the other two
      types. The methylation of other genes, CLIP4, XKR6, CCDC57, MAML3 and SDC2, was
      related with age, tumor location, or Helicobacter infection rather than the
      histologic subtype. Aberrant DNA methylation of certain genes may be
      independently involved in each histologic subtype of EGC. Furthermore, mixed-type
      EGCs may be a distinctive histologic subtype based on the different subset of
      DMRs compared to those of other subtypes.

PMID- 24737030
TI  - QSPR ensemble modelling of the 1:1 and 1:2 complexation of Co2+, Ni2+, and Cu2+
      with organic ligands: relationships between stability constants.
AB  - Quantitative structure-property relationship (QSPR) modeling of stability
      constants for the metal:ligand ratio 1:1 (logK) and 1:2 (logbeta2) complexes of 3
      transition metal ions with diverse organic ligands in aqueous solution was
      performed using ensemble multiple linear regression analysis and substructural
      molecular fragment descriptors. The modeling was performed on the sets containing
      396 and 132 (Co(2+)), 613 and 233 (Ni(2+)), 883 and 257 (Cu(2+)) logK and logbeta
      2 values, respectively. The models have been validated in external fivefold cross
      validations procedure as well as on the external test set containing new ligands
      recently reported in the literature. Predicted logK and logbeta 2 values were
      calculated as arithmetic means of several hundred individual models (consensus
      models) using their applicability domains in averaging. The root mean squared
      error of predictions varies from 0.94 to 1.2 (logK) and from 1.2 to 1.4
      (logbeta2) which is close to observed experimental systematic errors. Linear
      correlations between experimental logK values for pair of metal ions were
      evaluated. For all metal ions and ligands forming both 1:1 and 1:2 complexes the
      following ratio is observed: logbeta2/logK = 1.8 +/- 0.1, n = 492.

PMID- 24737031
TI  - Laparoscopic versus open total mesorectal excision for rectal cancer.
AB  - BACKGROUND: Colorectal cancer including rectal cancer is the third most common
      cause of cancer deaths in the western world. For colon carcinoma, laparoscopic
      surgery is proven to result in faster postoperative recovery, fewer complications
      and better cosmetic results with equal oncologic results. These short-term
      benefits are expected to be similar for laparoscopic rectal cancer surgery.
      However, the oncological safety of laparoscopic surgery for rectal cancer
      remained controversial due to the lack of definitive long-term results. Thus, the
      expected short-term benefits can only be of interest when oncological results are
      at least equal. OBJECTIVES: To evaluate the differences in short- and long-term
      results after elective laparoscopic total mesorectal excision (LTME) for the
      resection of rectal cancer compared with open total mesorectal excision (OTME).
      SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials
      (CENTRAL, The Cochrane Library 2013, Issue 2), MEDLINE (January 1990 to February
      2013), EMBASE (January 1990 to February 2013), ClinicalTrials.gov (February 2013)
      and Current Controlled Trials (February 2013). We handsearched the reference
      lists of the included articles for missed studies. SELECTION CRITERIA: Only
      randomised controlled trials (RCTs) comparing LTME and OTME, reporting at least
      one of our outcome measures, was considered for inclusion. DATA COLLECTION AND
      ANALYSIS: Two authors independently assessed study quality according to the
      CONSORT statement, and resolved disagreements by discussion. We rated the quality
      of the evidence using GRADE methods. MAIN RESULTS: We identified 45 references
      out of 953 search results, of which 14 studies met the inclusion criteria
      involving 3528 rectal cancer patients. We did not consider the risk of bias of
      the included studies to have impacted on the quality of the evidence. Data were
      analysed according to an intention-to-treat principle with a mean conversion rate
      of 14.5% (range 0% to 35%) in the laparoscopic group.There was moderate quality
      evidence that laparoscopic and open TME had similar effects on five-year disease
      free survival (OR 1.02; 95% CI 0.76 to1.38, 4 studies, N = 943). The estimated
      effects of laparoscopic and open TME on local recurrence and overall survival
      were similar, although confidence intervals were wide, both with moderate quality
      evidence (local recurrence: OR 0.89; 95% CI 0.57 to1.39 and overall survival
      rate: OR 1.15; 95% CI 0.87 to1.52). There was moderate to high quality evidence
      that the number of resected lymph nodes and surgical margins were similar between
      the two groups.For the short-term results, length of hospital stay was reduced by
      two days (95% CI -3.22 to -1.10), moderate quality evidence), and the time to
      first defecation was shorter in the LTME group (-0.86 days; 95% CI -1.17 to 
      0.54). There was moderate quality evidence that 30 days morbidity were similar in
      both groups (OR 0.94; 95% CI 0.8 to 1.1). There were fewer wound infections (OR
      0.68; 95% CI 0.50 to 0.93) and fewer bleeding complications (OR 0.30; 95% CI 0.10
      to 0.93) in the LTME group.There was no clear evidence of any differences in
      quality of life after LTME or OTME regarding functional recovery, bladder and
      sexual function. The costs were higher for LTME with differences up to GBP 2000
      for direct costs only. AUTHORS' CONCLUSIONS: We have found moderate quality
      evidence that laparoscopic total mesorectal excision (TME) has similar effects to
      open TME on long term survival outcomes for the treatment of rectal cancer. The
      quality of the evidence was downgraded due to imprecision and further research
      could impact on our confidence in this result. There is moderate quality evidence
      that it leads to better short-term post-surgical outcomes in terms of recovery
      for non-locally advanced rectal cancer. Currently results are consistent in
      showing a similar disease-free survival and overall survival, and for recurrences
      after at least three years and up to 10 years, although due to imprecision we
      cannot rule out superiority of either approach. We await long-term data from a
      number of ongoing and recently completed studies to contribute to a more robust
      analysis of long-term disease free, overall survival and local recurrence.

PMID- 24737033
TI  - Imaging findings in Down syndrome.
AB  - Down syndrome, or trisomy 21, is the most common chromosomal anomaly and is
      characterized by intellectual disability and a typical facies. People with Down
      syndrome can have abnormalities of multiple organ systems. Cardiac and
      respiratory system involvement is the most common cause of morbidity and
      mortality, although every organ system can be affected. Patients may present
      prenatally with findings on screening sonography. If the diagnosis is not made
      prenatally, it is apparent at birth because of the characteristic facial features
      and musculoskeletal findings. Children with Down syndrome present to the
      radiology department at various ages depending on the severity of the specific
      finding. The purpose of this paper is to review the most common antenatal and
      postnatal imaging findings of Down syndrome as they manifest throughout the body.

PMID- 24737035
TI  - Impairment in face processing in autism spectrum disorder: a developmental
      perspective.
AB  - Findings on face identity and facial emotion recognition in autism spectrum
      disorder (ASD) are inconclusive. Moreover, little is known about the
      developmental trajectory of face processing skills in ASD. Taking a developmental
      perspective, the aim of this study was to extend previous findings on face
      processing skills in a sample of adolescents and adults with ASD. N = 38
      adolescents and adults (13-49 years) with high-functioning ASD and n = 37
      typically developing (TD) control subjects matched for age and IQ participated in
      the study. Moreover, n = 18 TD children between the ages of 8 and 12 were
      included to address the question whether face processing skills in ASD follow a
      delayed developmental pattern. Face processing skills were assessed using
      computerized tasks of face identity recognition (FR) and identification of facial
      emotions (IFE). ASD subjects showed impaired performance on several parameters of
      the FR and IFE task compared to TD control adolescents and adults. Whereas TD
      adolescents and adults outperformed TD children in both tasks, performance in ASD
      adolescents and adults was similar to the group of TD children. Within the groups
      of ASD and control adolescents and adults, no age-related changes in performance
      were found. Our findings corroborate and extend previous studies showing that ASD
      is characterised by broad impairments in the ability to process faces. These
      impairments seem to reflect a developmentally delayed pattern that remains stable
      throughout adolescence and adulthood.

PMID- 24737036
TI  - [Anxiety disorders in DSM-5: an overview on changes in structure and content].
AB  - The Diagnostic and Statistical Manual of Mental Disorders 5 (DSM-5) "anxiety,
      obsessive-compulsive spectrum, posttraumatic, and dissociative disorders" work
      group addressed reconceptualization issues regarding all anxiety-related
      disorders. Based on systematic literature reviews, reanalyses of available data
      and evaluation of results following the DSM-5 principles it was decided to
      rearrange the disorder spectrum into separate groupings for the classical anxiety
      disorders, trauma- and stressor-related disorders, obsessive-compulsive and
      related disorders, and dissociative disorders. Among the classical anxiety
      disorders DSM-5 now also includes selective mutism and separation anxiety
      disorder. A major change from DSM-IV is a drastically simplified classification
      of panic disorder and agoraphobia. Both conditions can be separately coded in DSM
      5 and the overlap is disclosed by a comorbid double diagnosis. The anxiety
      disorder criteria have been generally harmonized regarding content and order. It
      was assured that criteria are applicable to all age, gender and cultural groups.
      Furthermore, diagnosis-specific and cross-cutting dimensional anxiety scales have
      been developed to supplement categorical diagnosis which appears to facilitate
      assessment of severity and course of treatment.

PMID- 24737037
TI  - [DSM-5: important changes in the field of addictive diseases].
AB  - There are two major changes in the Diagnostic and Statistical Manual of Mental
      Disorders (DSM-5) concerning the field of addiction. Firstly, the previous
      distinction between abuse and dependence has been abolished and both disorders
      are now subsumed under the category addiction and related disorders. Secondly,
      pathological gambling has now been included in the section of addiction with
      slight changes in diagnostic criteria. Both changes have major implications for
      the definition and conceptualization of what we call a psychiatric "disease" or
      "disorder", which have also been addressed in the introductory statement of DSM
      5. Concerning the category of abuse that is now part of substance use disorders,
      there is a concern that a well-defined disorder ("dependence") is now mixed with
      a less well-defined syndrome ("abuse"). The inclusion of non-substance,
      behavioral addictions poses the danger of pathologizing a wide range of human
      behavior in future revisions of the classification. Both concerns are further
      addressed in this article.

PMID- 24737038
TI  - A pilot feasibility study of neurofeedback for children with autism.
AB  - Neurofeedback (NFB) is an emerging treatment for children with autism spectrum
      disorder (ASD). This pilot study examined the feasibility of NFB for children
      with ASD. Ten children ages 7-12 with high functioning ASD and attention
      difficulties received a NFB attention training intervention. A standardized
      checklist captured feasibility, including focus during exercises and academic
      tasks, as well as off-task behaviors. Active behaviors and vocalizations were the
      most frequent off-task behaviors. Positive reinforcement and breaks including
      calm breathing exercises were the most common supports. Low motivation was
      associated with higher feasibility challenges, yet parental involvement and
      accommodations were helpful. This pilot study shows that it is feasible to
      conduct NFB sessions with children with high functioning autism and attention
      difficulties. 

PMID- 24737039
TI  - Identification of microorganisms based on headspace analysis of volatile organic
      compounds by gas chromatography-mass spectrometry.
AB  - The identification of specific volatile organic compounds (VOCs) produced by
      microorganisms may assist in developing a fast and accurate methodology for the
      determination of pulmonary bacterial infections in exhaled air. As a first step,
      pulmonary bacteria were cultured and their headspace analyzed for the total
      amount of excreted VOCs to select those compounds which are exclusively
      associated with specific microorganisms. Development of a rapid, noninvasive
      methodology for identification of bacterial species may improve diagnostics and
      antibiotic therapy, ultimately leading to controlling the antibiotic resistance
      problem. Two hundred bacterial headspace samples from four different
      microorganisms (Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus
      and Klebsiella pneumoniae) were analyzed by gas chromatography-mass spectrometry
      to detect a wide array of VOCs. Statistical analysis of these volatiles enabled
      the characterization of specific VOC profiles indicative for each microorganism.
      Differences in VOC abundance between the bacterial types were determined using
      ANalysis of VAriance-principal component analysis (ANOVA-PCA). These differences
      were visualized with PCA. Cross validation was applied to validate the results.
      We identified a large number of different compounds in the various headspaces,
      thus demonstrating a highly significant difference in VOC occurrence of bacterial
      cultures compared to the medium and between the cultures themselves.
      Additionally, a separation between a methicillin-resistant and a methicillin
      sensitive isolate of S. aureus could be made due to significant differences
      between compounds. ANOVA-PCA analysis showed that 25 VOCs were differently
      profiled across the various microorganisms, whereas a PCA score plot enabled the
      visualization of these clear differences between the bacterial types. We
      demonstrated that identification of the studied microorganisms, including an
      antibiotic susceptible and resistant S. aureus substrain, is possible based on a
      selected number of compounds measured in the headspace of these cultures. These
      in vitro results may translate into a breath analysis approach that has the
      potential to be used as a diagnostic tool in medical microbiology. 

PMID- 24737040
TI  - The hairpin conformation of the amyloid beta peptide is an important structural
      motif along the aggregation pathway.
AB  - The amyloid beta (Abeta) peptides are 39-42 residue-long peptides found in the
      senile plaques in the brains of Alzheimer's disease (AD) patients. These peptides
      self-aggregate in aqueous solution, going from soluble and mainly unstructured
      monomers to insoluble ordered fibrils. The aggregation process(es) are strongly
      influenced by environmental conditions. Several lines of evidence indicate that
      the neurotoxic species are the intermediate oligomeric states appearing along the
      aggregation pathways. This minireview summarizes recent findings, mainly based on
      solution and solid-state NMR experiments and electron microscopy, which
      investigate the molecular structures and characteristics of the Abeta peptides at
      different stages along the aggregation pathways. We conclude that a hairpin-like
      conformation constitutes a common motif for the Abeta peptides in most of the
      described structures. There are certain variations in different hairpin
      conformations, for example regarding H-bonding partners, which could be one
      reason for the molecular heterogeneity observed in the aggregated systems.
      Interacting hairpins are the building blocks of the insoluble fibrils, again with
      variations in how hairpins are organized in the cross-section of the fibril,
      perpendicular to the fibril axis. The secondary structure propensities can be
      seen already in peptide monomers in solution. Unfortunately, detailed structural
      information about the intermediate oligomeric states is presently not available.
      In the review, special attention is given to metal ion interactions, particularly
      the binding constants and ligand structures of Abeta complexes with Cu(II) and
      Zn(II), since these ions affect the aggregation process(es) and are considered to
      be involved in the molecular mechanisms underlying AD pathology. 

PMID- 24737041
TI  - Copper-induced structural propensities of the amyloidogenic region of human prion
      protein.
AB  - Transmissible spongiform encephalopathies are associated with the misfolding of
      the cellular Prion Protein (PrP(C)) to an abnormal protein isoform, called
      scrapie prion protein (PrP(Sc)). The structural rearrangement of the fragment of
      N-terminal domain of the protein spanning residues 91-127 is critical for the
      observed structural transition. The amyloidogenic domain of the protein encloses
      two copper-binding sites corresponding to His-96 and His-111 residues that act as
      anchors for metal ion binding. Previous studies have shown that Cu(II)
      sequestration by both sites may modulate the peptide's tendency to aggregation as
      it inflicts the hairpin-like structure that stabilizes the transition states
      leading to beta-sheet formation. On the other hand, since both His sites differ
      in their ability to Cu(II) sequestration, with His-111 as a preferred binding
      site, we found it interesting to test the role of Cu(II) coordination to this
      single site on the structural properties of amyloidogenic domain. The obtained
      results reveal that copper binding to His-111 site imposes precise backbone
      bending and weakens the natural tendency of apo peptide to beta-sheet formation. 

PMID- 24737044
TI  - Use of regulators and inhibitors of Pim-1, a serine/threonine kinase, for tumour
      therapy (review).
AB  - Pim-1 is a proto-oncogene that encodes a serine/threonine kinase that is
      overexpressed in a range of haematopoietic malignancies and solid cancers. Pim-1
      expression is tightly regulated by multiple biomolecules at different levels.
      Several lines of evidence have indicated that dysregulation of Pim-1 can
      interfere with the cell cycle and apoptosis to promote malignant transformation
      of a number of types of tumour. Thus, investigation of Pim-1 regulation may
      provide important theoretical guidance for the development of molecular targeting
      therapies and drug treatments for Pim-1-associated diseases. Regulators of Pim-1
      expression, include microRNAs, oestrogen, inecalcitol, adenosine triphosphate
      (ATP) mimetic inhibitors and ATP competitive inhibitors of Pim-1. Combinations of
      inhibitors of Pim-1 expression and Pim-1-specific inhibitors may provide novel
      therapies for cancer patients and directions for cancer treatment. 

PMID- 24737042
TI  - Synthesis, characterization, and evaluation of cis-diphenyl pyridineamine
      platinum(II) complexes as potential anti-breast cancer agents.
AB  - Although cisplatin is considered as an effective anti-cancer agent, it has shown
      limitations and may produce toxicity in patients. Therefore, we synthesized two
      cis-dichlorideplatinum(II) compounds (13 and 14) composed of meta- and para-N,N
      diphenyl pyridineamine ligands through a reaction of the amine precursors and
      PtCl2 with respective yields of 16 and 47 %. We hypothesized that compounds 13
      and 14, with lipophilic ligands, should transport efficiently in cancer cells and
      demonstrate more effectiveness than cisplatin. When tested for biological
      activity, compounds 13 and 14 were found to inhibit the growth of MCF 7 and MDA
      MB-231 cells (IC50s 1 +/- 0.4 uM and 1 +/- 0.2 uM for 13 and 14, respectively,
      and IC50 7.5 +/- 1.3 uM for compound 13 and 1 +/- 0.3 uM for compound 14).
      Incidentally, these doses were found to be lower than cisplatin doses (IC50 5 +/-
      0.7 uM for MCF 7 and 10 +/- 1.1 uM for MDA-MB-231). Similar to cisplatin, 13 and
      14 interacted with DNA and induced apoptosis. However, unlike cisplatin, they
      blocked the migration of MDA-MB-231 cells suggesting that in addition to
      apoptotic and DNA-binding capabilities, these compounds are useful in blocking
      the metastatic migration of breast cancer cells. To delineate the mechanism of
      action, computer-aided analyses (DFT calculations) were conducted for compound
      13. Results indicate that in vivo, the pyridineamine ligands are likely to
      dissociate from the complex, forming a platinum DNA adduct with anti
      proliferative activity. These results suggest that complexes 13 and 14 hold
      promise as potential anti-cancer agents.

PMID- 24737045
TI  - Blocking in human causal learning is affected by outcome assumptions manipulated
      through causal structure.
AB  - Additivity-related assumptions have been proven to modulate blocking in human
      causal learning. Typically, these assumptions are manipulated by means of
      pretraining phases (including exposure to different outcome magnitudes), or
      through explicit instructions. In two experiments, we used a different approach
      that involved neither pretraining nor instructional manipulations. Instead, we
      manipulated the causal structure in which the cues were embedded, thereby
      appealing directly to the participants' prior knowledge about causal relations
      and how causes would add up to yield stronger outcomes. Specifically, in our
      "different-system" condition, the participants should assume that the outcomes
      would add up, whereas in our "same-system" condition, a ceiling effect would
      prevent such an assumption. Consistent with our predictions, Experiment 1 showed
      that, when two cues from separate causal systems were combined, the participants
      did expect a stronger outcome on compound trials, and blocking was found, whereas
      when the cues belonged to the same causal system, the participants did not expect
      a stronger outcome on compound trials, and blocking was not observed. The results
      were partially replicated in Experiment 2, in which this pattern was found when
      the cues were tested for the second time. This evidence supports the claim that
      prior knowledge about the nature of causal relations can affect human causal
      learning. In addition, the fact that we did not manipulate causal assumptions
      through pretraining renders the results hard to account for with associative
      theories of learning. 

PMID- 24737046
TI  - The role of self-organization in developmental evolution.
AB  - In developmental and evolutionary biology, particular emphasis has been given to
      the relationship between transcription factors and the cognate cis-regulatory
      elements of their target genes. These constitute the gene regulatory networks
      that control expression and are assumed to causally determine the formation of
      structures and body plans. Comparative analysis has, however, established a broad
      sequence homology among species that nonetheless display quite different
      anatomies. Transgenic experiments have also confirmed that many developmentally
      important elements are, in fact, functionally interchangeable. Although dependent
      upon the appropriate degree of gene expression, the actual construction of
      specific structures appears not directly linked to the functions of gene products
      alone. Instead, the self-formation of complex patterns, due in large part to
      epigenetic and non-genetic determinants, remains a persisting theme in the study
      of ontogeny and regenerative medicine. Recent evidence indeed points to the
      existence of a self-organizing process, operating through a set of intrinsic
      rules and forces, which imposes coordination and a holistic order upon cells and
      tissue. This has been repeatedly demonstrated in experiments on regeneration as
      well as in the autonomous formation of structures in vitro. The process cannot be
      wholly attributed to the functional outcome of protein-protein interactions or to
      concentration gradients of diffusible chemicals. This phenomenon is examined here
      along with some of the methodological and theoretical approaches that are now
      used in understanding the causal basis for self-organization in development and
      its evolution. 

PMID- 24737047
TI  - Monometalated tribenzotriquinacene: exo and endo coordination of sodium and
      potassium with a rigid bowl-shaped hydrocarbon anion.
AB  - Treatment of tribenzotriquinacene with trimethylsilylmethyl sodium [NaCH2SiMe3]
      or potassium hydride [KH] leads to the formation of monometalated products. The
      sodium atom interacts with the carbanion in an exo fashion, while the potassium
      atom is found in an endo position inside the rigid bowl-shaped molecule. 

PMID- 24737048
TI  - Biomechanical analysis and design of a dynamic spinal fixator using topology
      optimization: a finite element analysis.
AB  - Surgeons often use spinal fixators to manage spinal instability. Dynesys (DY) is
      a type of dynamic fixator that is designed to restore spinal stability and to
      provide flexibility. The aim of this study was to design a new spinal fixator
      using topology optimization [the topology design (TD) system]. Here, we
      constructed finite element (FE) models of degenerative disc disease, DY, and the
      TD system. A hybrid-controlled analysis was applied to each of the three FE
      models. The rod structure of the topology optimization was modelled at a 39 %
      reduced volume compared with the rigid rod. The TD system was similar to the DY
      system in terms of stiffness. In contrast, the TD system reduced the cranial
      adjacent disc stress and facet contact force at the adjacent level. The TD system
      also reduced pedicle screw stresses in flexion, extension, and lateral bending. 

PMID- 24737049
TI  - Rapamycin inhibits Toll-like receptor 4-induced pro-oncogenic function in head
      and neck squamous cell carcinoma.
AB  - Toll-like receptor 4 (TLR4) is expressed in head and neck squamous cell carcinoma
      (HNSCC) cells and is associated with HNSCC cancer progression. Rapamycin has been
      proven to be efficient for the treatment of HNSCC in vivo, yet the mechanism is
      not understood and rapamycin demonstrates little effect in vitro. In the present
      study, the HNSCC cell lines CAL27 and SCC4 were pre-treated with rapamycin then
      stimulated with a TLR4 ligand lipopolysaccharide (LPS). Cell proliferation,
      migration, invasion, resistance to TRAIL-induced apoptosis, cytokine production,
      NF-kappaB and p65 activation were determined. The results indicated that LPS
      significantly stimulated HNSCC cell proliferation, cytokine production,
      migration, invasion and resistance to apoptosis induced by tumor necrosis factor
      (TNF)-related apoptosis-inducing ligand (TRAIL). Pretreatment with rapamycin
      significantly attenuated LPS-induced pro-oncogenic effects by inhibiting the
      activation of NF-kappaB by LPS. siRNA knockdown of TLR4 in HNSCC cells
      demonstrated that rapamycin attenuated LPS-induced pro-oncogenic effects via
      TLR4. Hence, this study suggests rapamycin may be efficient for the treatment of
      HNSCC by attenuating TLR4-induced pro-oncogenic effects. 

PMID- 24737050
TI  - 'Older women', customary obligations and orphan foster caregiving: the case of
      queen mothers in Manya Klo, Ghana.
AB  - Female orphan caregivers in countries heavily affected by HIV in sub-Saharan
      Africa are often presented as a homogenous group of vulnerable 'older women' that
      struggles to support orphans. There is a dearth of data on the different kinds of
      women and how their social characteristics impact their survival strategies and
      caregiving responsibilities. This study examines the link between the social
      characteristics of queen mothers in Manya Klo in Ghana and their roles as
      caregivers. The research findings suggest that queen mothers have become the
      primary caregivers of orphans, even though they do not have the wherewithal to
      provide for these orphans. The lack of kin support to queen mothers exacerbates
      their physical and economic vulnerabilities. They engage in less dignifying
      economic activities and pay less attention to their own needs in order to meet
      their customary obligations as orphan caregivers. The growing influence of queen
      mothers as caregivers for orphans, however, is a reflection of some of the
      changes that are occurring in customary foster care arrangements. Policy makers
      and interventionists require in depth understanding of queen mothers and their
      peculiar circumstances in order to strengthen their roles as leaders and
      caregivers. 

PMID- 24737051
TI  - Influence of closure, phenolic levels and microoxygenation on Cabernet Sauvignon
      wine composition after 5 years' bottle storage.
AB  - BACKGROUND: Wine aging is generally limited by the amount of oxidation, which is
      dependent on the amount of oxygen entering via the closure. Cabernet Sauvignon
      wine is well known for its high concentration of tannin, making it an ideal red
      wine for aging. The impact of closure type after 5 years' bottle aging has been
      investigated on a 2007 Cabernet Sauvignon red wine, treated with or without
      polyvinylpolypyrrolidone (PVPP) and micro-oxygenation (Mox). Two oxygen transfer
      rate (OTR) conditions (16 and 5 ug per day) into 375 mL bottles were obtained by
      using different synthetic stoppers. RESULTS: Color was evaluated by UV-visible
      spectrophotometry, carbonyls by 2,4-dinitrophenylhydrazine derivatization,
      phenolics by high-performance liquid chromatography and sulfur dioxide by the
      aspiration method. Closure type strongly influenced color parameters involving
      SO2 bleaching and some phenolics, particularly quercetin, were affected, but
      there was little effect on carbonyls other than acetaldehyde. PVPP treatment
      afforded wines with the lowest levels of phenolics and color density, but highest
      acetaldehyde. Few effects of Mox could be detected. CONCLUSIONS: Closure OTR
      strongly affects sulfur dioxide levels - the primary antioxidant in wine - in
      aged wine, but phenolic levels substantially alter the secondary reactions of
      oxidative aging.

PMID- 24737052
TI  - Genetic differentiation among populations of the Roseate Spoonbill (Platalea
      ajaja; Aves: Pelecaniformes) in three Brazilian Wetlands.
AB  - Effective population size, levels of genetic diversity, gene flow, and genetic
      structuring were assessed in 205 colonial Roseate spoonbills from 11 breeding
      colonies from north, central west, and south Brazil. Colonies and regions
      exhibited similar moderate levels of diversity at five microsatellite loci (mean
      expected heterozygosity range 0.50-0.62; allelic richness range 3.17-3.21). The
      central west region had the highest Ne (59). F ST values revealed low but
      significant genetic structuring among colonies within the north and within the
      south regions. Significant global genetic structuring was found between the
      northern and central western populations as well as between the northern and
      southern populations. An individual-based Bayesian clustering method inferred
      three population clusters. Assignment tests correctly allocated up to 64% of
      individuals to their source regions. Collectively, results revealed complex
      demographic dynamics, with ongoing gene flow on a local scale, but genetic
      differentiation on a broader scale. Populations in the three regions may all be
      conserved, but special concern should be given to central western ones, which can
      significantly contribute to the species' gene pool in Brazil. 

PMID- 24737053
TI  - Radionecrosis of the frontal lobe as a consequence of malignant ethmoid tumor
      management: incidence, diagnosis, risk factors, prevention and management.
AB  - Malignant ethmoid tumors are treated by surgery followed by radiotherapy. This
      study aimed to evaluate the incidence, risk factors and outcome of radionecrosis
      of frontal lobe and determine preventive measures. Retrospective study of ethmoid
      malignancies treated from 2000 to 2011. All patients underwent surgery
      with/without anterior skull base resection using endoscopic or external
      approaches followed by irradiation (mean dose 64 Gy). Median follow-up was 50
      months. Eight of 50 patients (16 %) presented with fronto-basal radionecrosis,
      connected to duraplasty, with a latent interval of 18.5 months. Although
      asymptomatic in six, radionecrosis triggered seizures and required surgery in two
      cases. Survival was not impacted. Risk factors included dyslipidemia, occurrence
      of epilepsy and dural resection. Radionecrosis may result from the combination of
      anterior skull base resection and radiotherapy for the treatment of ethmoid
      malignancies. Preventive measures rely on improving the duraplasty and
      optimization of the Gy-dose delivery.

PMID- 24737054
TI  - Post-tonsillectomy hemorrhage--some facts will never change.
AB  - Bleeding remains the most significant complication following tonsillectomy (TE),
      sometimes requiring revision surgery under general anesthesia. This study was
      undertaken to verify whether or not bleeding rates changed after bipolar
      coagulation was replaced by suture ligation to achieve hemostasis at a single
      institution. The charts of all patients who had undergone tonsillectomy between
      April 1, 2007, and April 30, 2013, at our institution were reviewed. The tonsils
      were bluntly dissected with scissors and a rasp. While hemostasis was achieved
      with bipolar coagulation during the first 36 months (group A), this method was
      replaced after a transition period of 1 month by intraoperative suture ligation
      (group B) during the last 36 months. Group A encompassed 2,137 patients including
      963 children scheduled for adenotonsillectomy (ATE), and group B consisted of
      1,521 patients and included 435 ATE cases. Bleeding from the tonsillar wounds
      occurred in 111/2,137 group A (5.2 %) and 68/1,521 group B patients (4.5 %). The
      difference was not found to be significant (p = 0.317). The incidence of primary
      bleeding (PB) and secondary bleeding (SB) was significantly (p = 0,000)
      associated with the method to achieve hemostasis: PB prevailed in group B and SB
      prevailed in group A. The overall incidence of post-tonsillectomy hemorrhage
      (PTH) varied at different ages, but the difference was not significant in group A
      (p = 0.401) and group B (p = 0.661). Repeated episodes of PTH occurred in 11/111
      group A (9.9 %) and 8/68 group B (11.7 %) patients. The statistical difference
      was not found to be significant (p = 0.725). However, there were significantly
      more male patients with bleeding complications in both groups. Despite the
      strongest efforts to avoid it, the potential risk of PTH remains a fact to be
      accepted by surgeons and patients. An increased surgical precision achieved by
      introduction of a surgical microscope as well as replacing bipolar cautery by
      suture ligation to achieve hemostasis could only reduce the overall rate of PTH.
      Another fact remains unchanged: PB occurs predominantly when electrosurgical
      means are avoided and SB prevails, whenever surgeons use them. We will continue
      our research on refined methods of cold steel microsurgical TE including suture
      techniques.

PMID- 24737055
TI  - Vestibular function and cochlear implant.
AB  - Vestibular lesions are found after cochlear implantation in 23-100 % of cases.
      The objectives of this study were to evaluate the vestibular function before and
      after implantation while focusing its feasibility. This prospective study
      included 35 patients, mean age 49 years. Each patient enjoyed a vestibular
      balance before and after implantation in a median period of 5 months compared to
      surgery. Vestibular evaluations were performed using vestibular-evoked myogenic
      potentials (VEMP) and videonystagmography. Before implantation, the VEMPs were
      bilateral in 73 % of cases. They are modified after implantation for 13 patients,
      including 12 missing or reduced potentials on implanted side (p = 0.0015).
      Caloric tests found themselves a significant decrease in the reflectivity of the
      ear implanted (p < 0.0001). Vestibular symptoms were independent of changes on
      vestibular tests. No relation was found between the occurrence of post-operative
      vestibular symptoms and the results of the vestibular investigations. However,
      the achievement of these exams is not easy especially for children and only part
      of the vestibule is tested. In conclusion, the vestibular assessments help to
      choose the side of implantation, assess the pre-operative vestibular condition
      and assess and locate vestibular lesions induced. Further tests should enable a
      complete vestibular assessment.

PMID- 24737056
TI  - TST, as a polysomnographic variable, is superior to the apnea hypopnea index for
      evaluating intermittent hypoxia in severe obstructive sleep apnea.
AB  - The polysomnography (PSG) index of the apnea hypopnea index (AHI) is considered
      the 'gold standard' for stratifying the severity of obstructive sleep apnea
      (OSA). However, AHI cannot reflect the true characteristic of chronic
      intermittent hypoxia (CIH), which may trigger systemic inflammation in some OSA
      patients. High-sensitivity C-reactive protein (hsCRP) is considered a biomarker
      of systemic inflammation in OSA patients. The aim of the present study was to
      evaluate the relationship between PSG variables and hsCRP in men with severe OSA.
      Men with severe OSA (AHI >= 30 events/h) diagnosed by PSG were enrolled. AHI and
      body mass index were matched between a high hsCRP group (hsCRP >= 3.0 mg/L) and a
      low hsCRP group. A blood sample was taken for serum hsCRP analysis. Multiple
      regression analysis was performed to assess independent predictors of high hsCRP.
      One hundred and fifty-two subjects were enrolled in the study (76 in each group).
      Mean serum hsCRP was 3.76 +/- 2.13 mg/L. The mean percentage of total sleep time
      spent with SaO2 <90% (TST) in the high hsCRP group was significantly higher than
      in the low hsCRP group (20.99 +/- 18.52 vs. 5.84 +/- 7.30, p < 0.001).
      Multivariate analysis showed that TST was the strongest predictor, contributing
      to 27.7% of hsCRP variability (beta = 0.496, p < 0.01). TST may be superior to
      AHI for evaluating CIH among OSA patients. The severity of OSA should be
      stratified by a combination of AHI and other hypoxia variables.

PMID- 24737058
TI  - Mn2+-deficiency reveals a key role for the Pleurotus ostreatus versatile
      peroxidase (VP4) in oxidation of aromatic compounds.
AB  - The manganese peroxidase gene family (mnps) is a part of the ligninolytic system
      of Pleurotus ostreatus. This gene family is comprised of nine members, mnp1-9,
      encoding short manganese peroxidases (short-MnPs) or versatile peroxidases (VPs).
      We show that unlike in Mn(2+)-amended glucose-peptone (GP) medium, where
      redundancy among mnps was reported, in Mn(2+)-deficient GP medium mnp4 [encoding
      versatile peroxidase isoenzyme 4 (VP4)] has a key and nonredundant function. The
      abundance of mnps transcripts at time points corresponding to the tropophase
      (active growth), early idiophase, and idiophase indicates that mnp4 is the
      predominantly expressed mnp gene and that its relative predominance is dependent
      on the age of the culture. In this medium, azo dye, Orange II (OII)
      decolorization occurs only during the idiophase and a Deltamnp4 strain showed a
      drastic reduction in this decolorization. Three degradation metabolites were
      identified by liquid chromatography-mass spectroscopy (LC-MS), indicating both
      asymmetric and symmetric enzymatic cleavage of the azo-bond. In addition, the
      culture filtrate of Deltamnp4 showed negligible values of oxidation capability of
      four typical VP substrates: Mn(2+), 2,6-dimethoxyphenol, phenol red, and Reactive
      Black 5 (RB5), compared to the wild-type strain PC9. We concluded that under
      Mn(2+)-deficient GP culture, VP4 (encoded by mnp4) is the main active
      ligninolytic enzyme able to oxidize Mn(2+) as well as high and low redox
      potential aromatic substrate, including dyes. Furthermore, other VPs/MnPs do not
      compensate for the lack of VP4 activity.

PMID- 24737057
TI  - Efficacy of novel antibacterial compounds targeting histidine kinase YycG
      protein.
AB  - Treating staphylococcal biofilm-associated infections is challenging. Based on
      the findings that compound 2 targeting the HK domain of Staphylococcus
      epidermidis YycG has bactericidal and antibiofilm activities against
      staphylococci, six newly synthesized derivatives were evaluated for their
      antibacterial activities. The six derivatives of compound 2 inhibited
      autophosphorylation of recombinant YycG' and the IC50 values ranged from 24.2 to
      71.2 MUM. The derivatives displayed bactericidal activity against planktonic S.
      epidermidis or Staphylococcus aureus strains in the MIC range of 1.5-3.1 MUM. All
      the derivatives had antibiofilm activities against the 6- and 24-h biofilms of S.
      epidermidis. Compared to the prototype compound 2, they had less cytotoxicity for
      Vero cells and less hemolytic activity for human erythrocytes. The derivatives
      showed antibacterial activities against clinical methicillin-resistant
      staphylococcal isolates. The structural modification of YycG inhibitors will
      assist the discovery of novel agents to eliminate biofilm infections and
      multidrug-resistant staphylococcal infections. 

PMID- 24737059
TI  - Highly thermostable and surfactant-activated chitinase from a subseafloor
      bacterium, Laceyella putida.
AB  - A novel chitinase (LpChiA) was purified to homogeneity from a culture of
      Laceyella putida JAM FM3001. LpChiA hydrolyzed colloidal chitin optimally at a pH
      of 4 in an acetate buffer and temperature of 75 oC. The enzyme was remarkably
      stable to incubation at 70 oC up to 1 h at pH 5.2, and its activity half-life was
      3 days. The molecular mass of the enzyme was around 38 kDa by sodium dodecyl
      sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and around 75 kDa by gel
      filtration, suggesting it is a homodimer. The enzyme activity was enhanced about
      60% when pre-incubated with anionic, cationic, and nonionic surfactants. The gene
      for LpChiA was cloned by PCR and sequenced. The nucleotide sequence of the gene
      consisted of 1,683 bp encoding 560 amino acids. The N-terminal and internal amino
      acid sequences of the purified LpChiA from L. putida suggested that the mature
      enzyme was composed of 384 amino acids after cleaving its 176 N-terminal amino
      acids and dimerized to express its activity. The deduced amino acid sequence of
      the mature enzyme showed the highest similarity to chitinase of Laceyella
      sacchari with 79% identity.

PMID- 24737060
TI  - Evaluation and screening of efficient promoters to improve astaxanthin production
      in Xanthophyllomyces dendrorhous.
AB  - Astaxanthin is a valuable carotenoid that is widely used in the aquaculture,
      food, pharmaceutical, and cosmetic industries. Xanthophyllomyces dendrorhous is a
      carotenoid-synthesizing yeast strain that produces astaxanthin as its main
      pigment. Although metabolic engineering using gene manipulation is a valuable way
      to improve astaxanthin production, a gene expression system for X. dendrorhous
      has been poorly developed. In this study, three known promoters of X.
      dendrorhous, glycerol-3-phosphate dehydrogenase (gpd) promoter (Pgpd), glucose
      dehydrogenase (gdh) promoter (Pgdh), and actin (act) promoter (Pact), were
      evaluated for use in the overexpression of target proteins using green
      fluorescence protein (GFP) as an expression level indicator protein. The actin
      promoter, Pact, showed the highest expression level of GFP when compared with
      Pgpd and Pgdh. Additionally, to obtain new promoters for higher expression of
      target protein in X. dendrorhous, intracellular GFP intensity was evaluated for
      13 candidate promoters. An alcohol dehydrogenase promoter, Padh4, showed more
      efficient expression of GFP rather than Pact. Overexpression of crtE gene
      encoding rate-limiting enzyme of carotenoid synthesis under the adh4 promoter
      yielded an increase in intracellular astaxanthin content of about 1.7-fold
      compared with the control strain. The promoters identified in this study must be
      useful for improving carotenoids production in X. dendrorhous.

PMID- 24737061
TI  - Filamentous fungi in microtiter plates-an easy way to optimize itaconic acid
      production with Aspergillus terreus.
AB  - Itaconic acid is an important industrial building block and is produced by the
      filamentous fungi Aspergillus terreus. To make the optimization process more
      efficient, a scale-down from shake flasks to microtiter plates was performed.
      This resulted in comparable product formations, and 87.7 g/L itaconic acid was
      formed after 10 days of cultivation in the microtiter plate. The components of
      the minimal medium were varied independently for a media optimization. This
      resulted in an increase of the itaconic acid concentration by a variation of the
      KH2PO4 and CuSO4 concentrations. The cultivation with a higher KH2PO4
      concentration in a 400-mL bioreactor showed an increase in the maximum
      productivity of 1.88 g/L/h, which was an increase of 74 % in comparison to the
      reference. Neither the phosphate concentration nor the nitrogen sources were
      limited at the start of the product formation. This showed that a limitation of
      these substances is not necessary for the itaconic acid formation. 

PMID- 24737062
TI  - Classification of motor imagery performance in acute stroke.
AB  - OBJECTIVE: Effective motor imagery performance, seen as strong suppression of the
      sensorimotor rhythm, is the key element in motor imagery therapy. Therefore,
      optimization of methods to classify whether the subject is performing the imagery
      task is a prerequisite. An optimal classification method should have high
      performance accuracy and use a small number of channels. We investigated the
      additional benefit of the common spatial pattern filtering (CSP) to a linear
      discriminant analysis (LDA) classifier, for different channel configurations.
      METHODS: Ten hemispheric acute stroke patients and 11 healthy subjects were
      included. EEGs were recorded using 60 channels. The classifier was trained with a
      motor execution task. For both healthy controls and patients, analysis of
      recordings was initially limited to 3 and 11 electrodes recording from the motor
      cortex area, and later repeated using 45 electrodes. RESULTS: No significant
      improvement on the addition of CSP to LDA was found (in both cases, the area
      under the receiving operating characteristic (AU-ROC) ~ 0.70 (acceptable)). We
      then repeated the LDA+CSP method on recordings of 45 electrodes, since the use of
      imagery neuronal circuits may well extend beyond the motor area. AU-ROC rose to
      0.90, but no virtual 'most responsible' electrode was observed. Finally, in mild
      to-moderate stroke patients we could successfully use the EEG data recorded from
      the healthy hemisphere to train the classifier (AU-ROC ~ 0.70). SIGNIFICANCE:
      Including only the channels on the unaffected motor cortex is sufficient to train
      a classifier.

PMID- 24737063
TI  - Membrane hyperpolarization during human sperm capacitation.
AB  - Sperm capacitation is a complex and indispensable physiological process that
      spermatozoa must undergo in order to acquire fertilization capability.
      Spermatozoa from several mammalian species, including mice, exhibit a
      capacitation-associated plasma membrane hyperpolarization, which is necessary for
      the acrosome reaction to occur. Despite its importance, this hyperpolarization
      event has not been adequately examined in human sperm. In this report we used
      flow cytometry to show that a subpopulation of human sperm indeed undergo a
      plasma membrane hyperpolarization upon in vitro capacitation. This
      hyperpolarization correlated with two other well-characterized capacitation
      parameters, namely an increase in intracellular pH and Ca(2+) concentration,
      measured also by flow cytometry. We found that sperm membrane hyperpolarization
      was completely abolished in the presence of a high external K(+) concentration
      (60 mM), indicating the participation of K(+) channels. In order to identify,
      which of the potential K(+) channels were involved in this hyperpolarization, we
      used different K(+) channel inhibitors including charybdotoxin, slotoxin and
      iberiotoxin (which target Slo1) and clofilium (a more specific blocker for Slo3).
      All these K(+) channel antagonists inhibited membrane hyperpolarization to a
      similar extent, suggesting that both members of the Slo family may potentially
      participate. Two very recent papers recorded K(+) currents in human sperm
      electrophysiologically, with some contradictory results. In the present work, we
      show through immunoblotting that Slo3 channels are present in the human sperm
      membrane. In addition, we found that human Slo3 channels expressed in CHO cells
      were sensitive to clofilium (50 MUM). Considered altogether, our data indicate
      that Slo1 and Slo3 could share the preponderant role in the capacitation
      associated hyperpolarization of human sperm in contrast to what has been
      previously reported for mouse sperm, where Slo3 channels are the main
      contributors to the hyperpolarization event. 

PMID- 24737064
TI  - Investigation of chronic musculoskeletal pain (third report): with special
      reference to the importance of neuropathic pain and psychogenic pain.
AB  - BACKGROUND: The previous epidemiological surveys conducted in Japan revealed that
      once the vicious cycle of chronic musculoskeletal pain begins, it is difficult to
      disrupt the cycle. This finding suggests the existence of problems with the
      conventional approaches to treatment of chronic musculoskeletal pain. The purpose
      of this study was to investigate the characteristics of patients with chronic
      musculoskeletal pain focusing on neuropathic and psychogenic pain. METHODS: The
      questionnaire was sent again to the 660 subjects found to have persistent chronic
      pain in the epidemiological surveys conducted in 2011. Responses were collected
      from 588 subjects (response rate 90%). RESULTS: Of the 588 responders, 365 (62%)
      complained of persistent chronic pain. Among them, 128 (35%) were still receiving
      treatment and 193 (53%) had discontinued treatment. The degree of satisfaction
      with the treatment was low, and 66% of the patients had switched the medical
      facility that they visited to receive treatment. The cited reasons for the change
      in the medical facility visited and discontinuation of treatment were "treatment
      was ineffective," "I did not have sufficient time," "I thought I could take care
      of it myself," and "Treatment seemed to be unnecessary". Involvement of
      neuropathic pain was suggested in 20% of all the patients with chronic pain. As
      the PainDETECT Score rose, the Visual Analog Scale (VAS) score became higher and
      the change of medical facility for treatment also increased. The Pain
      Catastrophizing Scale score was correlated positively with the VAS score. The
      Hospital Anxiety and Depression Scale score was significantly correlated with the
      VAS score and the duration of pain. DISCUSSION: The results of this survey
      indicated that the chronic course of musculoskeletal pain may be attributable to
      the following factors: (1) lack of appropriate treatment of neuropathic pain and
      psychogenic pain, and (2) insufficient awareness/knowledge among patients about
      chronic musculoskeletal pain.

PMID- 24737065
TI  - The role of expectancies in the size-weight illusion: a review of theoretical and
      empirical arguments and a new explanation.
AB  - The size-weight illusion (SWI) refers to the phenomenon that objects that are
      objectively equal in weight but different in size or volume are perceived to
      differ in weight, such that smaller objects feel heavier than larger ones. This
      article reviews studies trying to support three different viewpoints with respect
      to the role of expectancies in causing the SWI. The first viewpoint argues for a
      crucial role; the second admits a role, yet without seeing consequences for
      sensorimotor processes; and the third denies any causal role for expectancies at
      all. A new explanation of the SWI is proposed that can integrate the different
      arguments. A distinctive feature of the new explanation is that it recognizes the
      causal influence of expectancies, yet combines this with certain reactive and
      direct behavioral consequences of perceiving size differences that are
      independent of experience-based expectancies, and that normally result in the
      adaptive application of forces to lift or handle differently sized objects. The
      new account explains why the illusion is associated with the repeated generation
      of inappropriate lifting forces (which can, however, be modified through
      extensive training), as well as why it depends on continuous visual exposure to
      size cues, appears at an early age, and is cognitively impenetrable. 

PMID- 24737066
TI  - Self-assembly and cooperative dynamics of a model colloidal gel network.
AB  - We study the assembly into a gel network of colloidal particles, via effective
      interactions that yield local rigidity and make dilute network structures
      mechanically stable. The self-assembly process can be described by a Flory
      Huggins theory, until a network of chains forms, whose mesh size is on the order
      of, or smaller than, the persistence length of the chains. The localization of
      the particles in the network, akin to some extent to caging in dense glasses, is
      determined by the network topology, and the network restructuring, which takes
      place via bond breaking and recombination, is characterized by highly cooperative
      dynamics. We use NVE and NVT molecular dynamics as well as Langevin dynamics and
      find a qualitatively similar time dependence of time correlations and of the
      dynamical susceptibility of the restructuring gel. This confirms that the
      cooperative dynamics emerge from the mesoscale organization of the network. 

PMID- 24737067
TI  - Structure-activity relationship of 1-desamino-8-D-arginine vasopressin as an
      antiproliferative agent on human vasopressin V2 receptor-expressing cancer cells.
AB  - The synthetic nonapeptide 1-desamino-8-D-arginine vasopressin (dDAVP) can reduce
      tumor cell growth through agonist action on the vasopressin V2 receptor. A
      structure-antiproliferative activity relationship analysis of dDAVP was performed
      using the alanine scanning technique on the aggressive MDA-MB-231 human breast
      carcinoma cell line. The results from this analysis demonstrated that the amino
      acids located at the loop of dDAVP are important for the antiproliferative
      activity of dDAVP, highlighting the key role of the N-terminal region of the
      peptide in the interaction with the tumor cell surface receptor. The findings
      from this study present novel strategies for designing improved compounds with
      enhanced stability for cancer therapy. 

PMID- 24737068
TI  - [The importance of risk models for management of pulmonary nodules].
AB  - CLINICAL/METHODICAL ISSUE: Pulmonary nodules are a frequent finding in computed
      tomography (CT) investigations. STANDARD RADIOLOGICAL METHODS: Further diagnostic
      work-up of detected nodules mainly depends on the so-called pre-test probability,
      i.e. the probability that the nodule is malignant or benign. METHODICAL
      INNOVATIONS: The pre-test probability can be calculated by combining all relevant
      information, such as the age and the sex of the patient, the smoking history, and
      history of previous malignancies, as well as the size and CT morphology of the
      nodule. PERFORMANCE: If additional investigations are performed to further
      investigate the nodules, all results must be interpreted taking into account the
      pre-test probability and the test performance of the investigation in order to
      estimate the post-test probability. ACHIEVEMENTS: In cases with a low pre-test
      probability, a negative result from an exact test can exclude malignancies but a
      positive test cannot prove malignancy in such a setting. In cases with a high pre
      test probability, a positive test result can be considered as proof of malignancy
      but a negative test result does not exclude malignancy.

PMID- 24737070
TI  - Enhancing Corynebacterium glutamicum robustness by over-expressing a gene, mshA,
      for mycothiol glycosyltransferase.
AB  - Over-expression of the gene, mshA, coding for mycothiol glycosyl transferase
      improved the robustness of Corynebacterium glutamicum to various stresses.
      Intracellular mycothiol (MSH) content was increased by 114 % in WT(pXMJ19-mshA)
      compared to WT(pXMJ19). Survival rates increased by 44, 39, 90, 77, 131, 87, 52,
      47, 57, 85 and 33 % as compared to WT(pXMJ19) under stress by H2O2 (40 mM),
      methylglyoxal (5.8 mM), erythromycin (0.08 mg ml(-1)), streptomycin (0.005 mg ml(
      1)), Cd(2+) (0.01 mM), Mn(2+) (2 mM), formic acid (0.05 %), acetic acid (0.15 %),
      levulinic acid (0.25 %), furfural (7.2 mM), and ethanol (10 % v/v), respectively.
      Increased MSH content also decreased the concentration of reactive oxygen species
      in the presence of the above stresses. Our results may open a new avenue for
      enhancing robustness of industrial bacteria for production of commodity
      chemicals. 

PMID- 24737069
TI  - Stromal expression of carbonic anhydrase IX in esophageal cancer.
AB  - PURPOSE: Carbonic anhydrase IX (CA IX), a transmembrane glycoprotein, is known as
      an endogenous marker for hypoxia. Overexpressed in cancer-associated fibroblasts,
      CA IX has been reported to be associated with a poor outcome for a number of
      malignant tumors. Aim of this study was to investigate the role of CA IX in the
      tumor surrounding stroma of esophageal cancer. METHODS/PATIENTS: Stromal
      expression of CA IX in 361 formalin-fixed, paraffin-embedded specimens of
      invasive esophageal cancers, 206 adenocarcinoma (AC) and 155 squamous cell
      carcinoma (SCC), was investigated. RESULTS: In 42 cases (11.6 %), CA IX
      expression in the tumor surrounding stroma (AC 23 and SCC 19) was observed.
      Expression of CA IX correlated with the factors tumor stage (p < 0.001) and lymph
      node status (p = 0.008). Patients with CA IX expressed in the tumor surrounding
      stroma had a significant shorter disease-free survival (p = 0.007) and overall
      survival (p = 0.013). CONCLUSION: In esophageal cancer, CA IX-expressing tumor
      stroma is associated with shorter survival. Inhibition of the tyrosine kinase CA
      IX might represent a new onset for therapies against esophageal cancer.

PMID- 24737071
TI  - KfoE encodes a fructosyltransferase involved in capsular polysaccharide
      biosynthesis in Escherichia coli K4.
AB  - Escherichia coli K4 synthesizes a capsular polysaccharide (CPS) consisting of a
      fructose-branched chondroitin (GalNAc-GlcA(fructose)n), which is a biosynthetic
      precursor of chondroitin sulfate. Here, the role of kfoE in the modification of
      the chondroitin backbone was investigated using knock-out and recombinant
      complementation experiments. kfoE disruption and complementation had no
      significant effect on cell growth. CPS production was increased by 15 % in the
      knock-out strain, and decreased by 21 % in the knock-out strain complemented with
      recombinant kfoE. CPS extracted from the knock-out strain was chondroitin,
      whereas CPS extracted from the complemented strain was a fructose-branched
      chondroitin. The results demonstrated that the kfoE gene product altered the
      fructose group at the C3 position of the GlcA residue during production of K4CPS.

PMID- 24737072
TI  - Fermentative H2 production from residual glycerol: a review.
AB  - The fermentative production of H2 from residual glycerol is an attractive
      alternative for clean energy production from a waste product. Selection of
      operational variables for microbial populations with an adequate diversity in
      order to improve H2 yields is an issue faced during optimization of biological
      production of H2. Operational and environmental factors affect both microbial
      diversity and the activity of specific enzymes. Therefore, these variables must
      be controlled to obtain the best H2 yields. This review covers the main variables
      involved in the fermentative production of H2 from crude glycerol and the
      biochemistry of the anaerobic digestion of glycerol, with a focus on the
      microbial diversity involved in this process. 

PMID- 24737073
TI  - Quorum sensing activity and control of yeast-mycelium dimorphism in Ophiostoma
      floccosum.
AB  - Quorum sensing (QS) activity in Ophiostoma fungi has not been described. We have
      examined the growth conditions on the control of dimorphism in Ophiostoma
      floccosum, an attractive biocontrol agent against blue-stain fungi, and its
      relationship with QS activity. In a defined culture medium with L-proline as the
      N source, a high inoculum size (10(7) c.f.u. ml(-1)) was the principal factor
      that promoted yeast-like growth. Inoculum size effect can be explained by the
      secretion of a QS molecule(s) (QSMs) responsible for inducing yeast morphology.
      QSM candidates were extracted from spent medium and their structure was
      determined by GC-MS. Three cyclic sesquiterpenes were found. The most abundant
      molecule, and therefore the principal candidate to be the QSM responsible for
      yeast growth of O. floccosum, was 1,1,4a-trimethyl-5,6-dimethylene-decalin
      (C15H24). Other two compounds were also detected. 

PMID- 24737074
TI  - Effect of photoperiod, light intensity and carbon sources on biomass and lipid
      productivities of Isochrysis galbana.
AB  - Biomass and lipid productivities of Isochrysis galbana were optimized using
      nutrients of molasses (4, 8, 12 g l(-1)), glucose (4, 8, 12 g l(-1)), glycerol
      (4, 8, 12 g l(-1)) and yeast extract (2 g l(-1)). Combinations of carbon sources
      at different ratios were evaluated in which the alga was grown at three different
      light intensities (50, 100 and 150 MUmol m(-2) s(-1)) under the influence of
      three different photoperiod cycles (12/12, 18/6 and 24/0 h light/dark). A maximum
      cell density of 8.35 g l(-1) with 32 % (w/w) lipid was achieved for mixotrophic
      growth at 100 MUmol m(-2) s(-1) and 18/6 h light/dark with molasses/glucose
      (20:80 w/w). Mixotrophic cultivation using molasses, glucose and glycerol was
      thus effective for the cultivation of I. galbana.

PMID- 24737075
TI  - Purification and characterization of a thermostable lambda-carrageenase from a
      hot spring bacterium, Bacillus sp.
AB  - Purpose of work The purpose of this study is to report a thermostable lambda
      carrageenase that can degrade lambda-carrageenan yielding neo-lambda-carrabiose
      at 75  degrees C.A thermophilic strain Lc50-1 producing lambda-carrageenase was
      isolated from a hot spring in Indonesia and identified as a Bacillus sp. The
      lambda-carrageenase, Cga-L50, with an apparent molecular weight of 37 kDa and a
      specific activity of 105 U/mg was purified from the culture supernatant. The
      optimum pH and temperature of Cga-L50 were 8.0 and 75  degrees C, respectively.
      The enzyme was stable from pH 6-9 and retained ~50 % activity after holding at 85
      degrees C for 10 min. Significant activation of Cga-L50 was observed with K(+),
      Ca(2+), Co(2+), and Na(+); whereas, the enzyme activity was inhibited by Sr(2+),
      Mn(2+), Fe(2+), Cu(2+),Cd(2+), Mg(2+), and EDTA. Cga-L50 is an endo-type lambda
      carrageenase that hydrolyzes beta-1,4-linkages of lambda-carrageenan, yielding
      neo-lambda-carrabiose as the main product. This study is the first to present
      evidence of thermostable lambda-carrageenase from hot spring bacteria.

PMID- 24737076
TI  - Protective effects of a wheat germ peptide (RVF) against H2O 2-induced oxidative
      stress in human neuroblastoma cells.
AB  - RVF (Arg-Val-Phe), a peptide derived from wheat germ, shows antioxidant
      properties. Here, the neuroprotective efficacies of RVF were investigated in
      human neuroblastoma cells (SH-SY5Y) that were pretreated with RVF (150-250 MUM, 4
      h) and exposed to H2O2 (200 MUM). RVF increased viable cell numbers by 37 % and
      reduced the release of lactate dehydrogenase. Pretreatment with RVF also
      inhibited H2O2-induced accumulation of reactive oxygen species and maintained the
      mitochondrial transmembrane potential as well as preventing intracellular Ca(2+)
      dysregulation during H2O2 exposure. Furthermore, pretreatment with RVF increased
      the Bcl-2/Bax ratio and blocked cleavage poly(ADP-ribose) polymerase by
      inhibiting caspase-3 activation, thus decreasing apoptosis.

PMID- 24737077
TI  - Over-expression of PsGPD, a mushroom glyceraldehyde-3-phosphate dehydrogenase
      gene, enhances salt tolerance in rice plants.
AB  - Transgenic potatoes expressing glyceraldehyde-3-phosphate dehydrogenase (GPD),
      isolated from the oyster mushroom, Pleurotus sajor-caju, had increased tolerance
      to salt stress (Jeong et al. Biochem Biophys Res Commun 278:192-196, 2000). To
      examine the physiological mechanisms enhancing salt tolerance in GPD-transgenic
      rice plants, the salt tolerance of five GPD transgenic rice lines (T1-T5) derived
      from Dongjin rice cultivar were evaluated in a fixed 150 mM saline environment in
      comparison to two known wild-type rice cultivars, Dongjin (salt sensitive) and
      Pokali (salt tolerant). Transgenic lines, T2, T3, and T5, had a substantial
      increase in biomass and relative water content compared to Dongjin. Stomatal
      conductance and osmotic potential were higher in the GPD transgenic lines and
      were similar to those in Pokali. The results are discussed based on the
      comparative physiological response of GPD transgenic lines with those of the salt
      sensitive and salt-tolerant rice cultivars.

PMID- 24737078
TI  - Identifying and engineering promoters for high level and sustainable therapeutic
      recombinant protein production in cultured mammalian cells.
AB  - Promoters are essential on plasmid vectors to initiate transcription of the
      transgenes when generating therapeutic recombinant proteins expressing mammalian
      cell lines. High and sustained levels of gene expression are desired during
      therapeutic protein production while gene expression is useful for cell
      engineering. As many finely controlled promoters exhibit cell and product
      specificity, new promoters need to be identified, optimized and carefully
      evaluated before use. Suitable promoters can be identified using techniques
      ranging from simple molecular biology methods to modern high-throughput omics
      screenings. Promoter engineering is often required after identification to either
      obtain high and sustained expression or to provide a wider range of gene
      expression. This review discusses some of the available methods to identify and
      engineer promoters for therapeutic recombinant protein expression in mammalian
      cells. 

PMID- 24737079
TI  - Silk screen based dual spin-filter module for perfusion culture of adherent and
      non-adherent mammalian cells.
AB  - Spin-filters have been primarily used for producing therapeutic proteins from
      mammalian cells. However, disposability and/or high filter clogging of the
      existing spin-filter systems affect the process economy and productivity. Hence,
      to address these drawbacks a reusable dual spin-filter module for perfusion
      culture of adherent and non-adherent mammalian cells was designed. Two non-woven
      Bombyx mori silk layers were used as filter screen; the outer layer was conducive
      to cell attachment whilst the inner was non-conducive. Adherent cells can be
      cultured either in suspended mode using its inner single module or as monolayer
      of cells using its dual concentric module. We achieved 30 % higher urokinase
      productivity as compared to the stainless-steel spin-filter during perfusion
      experiments of adherent human kidney cells in suspended mode. This was due to the
      hydrophobic and negatively-charged silk screen that allows clog-free perfusion
      culture for prolonged periods.

PMID- 24737080
TI  - A strategy for fusion expression and preparation of functional glucagon-like
      peptide-1 (GLP-1) analogue by introducing an enterokinase cleavage site.
AB  - KGLP-1, a 31-amino acid glucagon-like peptide-1 (GLP-1) analogue, has a great
      therapeutic potential for anti-diabetes. In this work, a strategy for expression
      and purification of functional KGLP-1 peptide has been established. KGLP-1 cDNA
      was fused with glutathione S-transferase (GST), with an enterokinase cleavage
      site in the fusion junction. The recombinant fusion protein GST-KGLP-1 was
      affinity purified via the GST-tag, and then digested with enterokinase. The
      resulting GST part as well as the enzymes were eliminated by ultra-filtration
      followed by size exclusion chromatograph. The yield of purified KGLP-1 was
      approximately 12.1 mg/L, with purity of 96.18 %. The recombinant KGLP-1 was shown
      to have similar bioactivity as native GLP-1 when evaluated in a Chinese hamster
      ovary cell line expressing a GLP-1 receptor-egfp reporter gene.

PMID- 24737081
TI  - Synthesis of beta-alanine from L-aspartate using L-aspartate-alpha-decarboxylase
      from Corynebacterium glutamicum.
AB  - beta-Alanine is mainly produced by chemical methods in current industrial
      processes. Here, panD from Corynebacterium glutamicum encoding L-aspartate-alpha
      decarboxylase (ADC) was cloned and expressed in Escherichia coli BL21(DE3). ADC
      C.g catalyzes the alpha-decarboxylation of L-aspartate to beta-alanine. The
      purified ADC C.g was optimal at 55  degrees C and pH 6 with excellent stability
      at 16-37  degrees C and pH 4-7. A pH-stat directed, fed-batch feeding strategy
      was developed for enzymatic synthesis of beta-alanine to keep the pH value within
      6-7.2 and thus attenuate substrate inhibition. A maximum conversion of 97.2 % was
      obtained with an initial 5 g L-aspartate/l and another three feedings of 0.5 %
      (w/v) L-aspartate at 8 h intervals. The final beta-alanine concentration was
      12.85 g/l after 36 h. This is the first study concerning the enzymatic production
      of beta-alanine by using ADC.

PMID- 24737082
TI  - Enhanced production of ATP-binding cassette protein exporter-dependent lipase by
      modifying the growth medium components of Pseudomonas fluorescens.
AB  - The industrially-important thermostable lipase, TliA, was extracellularly
      produced in the recombinant Pseudomonas fluorescens by the homologous expression
      of TliA and its cognate ABC protein exporter, TliDEF. To increase the secretory
      production of TliA, we optimized the growth temperature and the culture medium of
      P. fluorescens. The total amount and the specific productivity of lipase was
      highest at 25  degrees C of cell growth temperature, although maximal cell growth
      was observed at 30  degrees C. Using the culture medium composed of 20 g dextrin
      l(-1), 40 g Tween 80 l(-1) and 30 g peptone l(-1), TliA was produced at a level
      of 2,200 U ml(-1) in a flask culture. The TliA production increased about 3.8
      fold (8,450 U ml(-1)) in batch fermentation using a 2.5 l fermentor, which was
      about 7.7-fold higher than that of previously reported TliA production.

PMID- 24737083
TI  - Construction of dextrin and isomaltose-assimilating brewer's yeasts for
      production of low-carbohydrate beer.
AB  - Most Saccharomyces spp. cannot degrade or ferment dextrin, which is the second
      most abundant carbohydrate in wort for commercial beer production. Dextrin
      degrading brewer's bottom and top yeasts expressing the glucoamylase gene (GAM1)
      from Debaryomyces occidentalis were developed to produce low-carbohydrate
      (calorie) beers. GAM1 was constitutively expressed in brewer's yeasts using a
      rDNA-integration system that contained yeast CUP1 gene coding for copper
      resistance as a selective marker. The recombinants secreted active glucoamylase,
      displaying both alpha-1,4- and alpha-1,6-debranching activities, that degraded
      dextrin and isomaltose and consequently grew using them as sole carbon source.
      One of the recombinant strains expressing GAM1 hydrolyzed 96 % of 2 % (w/v)
      dextrin and 98 % of 2 % (w/v) isomaltose within 5 days of growth. Growth,
      substrate assimilation, and enzyme activity of these strains were characterized.

PMID- 24737084
TI  - Cloning and characterization of a novel GH44 family endoglucanase from mangrove
      soil metagenomic library.
AB  - A novel endoglucanase gene, mgcel44, was isolated from a mangrove soil
      metagenomic library by functional-based screening. It encodes a 648-aa peptide
      with a catalytic domain of glycosyl hydrolase family 44. The deduced amino acid
      sequence of mgcel44 shares less than 50 % identity with endoglucanases in GenBank
      database. mgcel44 was cloned and overexpressed in Escherichia coli. The
      recombinant enzyme, MgCel44, has a molecular mass of 70.8 kDa as determined by
      SDS-PAGE. Its optimal pH and temperature for activity were 6 and 45  degrees C,
      respectively. It was highly active at 25-45  degrees C and pH 5-8. Its activity
      was enhanced in 0.5 M NaCl by >1.6-fold and stable up to 1.5 M NaCl. MgCel44 was
      resistant to several organic solvents and had high activity at 15 % (v/v) solvent
      after incubating for 24 h at 25  degrees C.

PMID- 24737085
TI  - Aberrant histone methylation and the effect of Suv39H1 siRNA on gastric
      carcinoma.
AB  - The present study aimed to investigate the involvement of the Suv39H1 histone
      methyltransferase in the epigenetic changes in the euchromatic promoter in
      gastric carcinoma. We retrospectively analyzed the protein of Suv39H1 and tri
      methylated histone H3 lysine 9 (H3K9) and histone H3 lysine 4 (H3K4) in 175 cases
      of gastric carcinoma by immunohistochemistry. Suv39H1 was depleted by siRNA, and
      cell apoptosis and cell proliferation were assessed by TUNEL and MTT assays,
      respectively. Histone methylated H3K9 and histone acetylated H3 and H4 were
      evaluated by western blotting. We found that the expression of Suv39H1 and tri
      methylated H3K9 in gastric carcinoma was higher than that in benign gastric
      diseases (p<0.05). Tri-methylated H3K4 was similar in both tissue types (p>0.05).
      Both Suv39H1 and tri-methylated H3K9 were positively correlated with the degree
      of differentiation, depth of infiltration and lymphatic invasion (p<0.05) in
      gastric carcinoma. In addition, tri-methylated H3K9 was positively correlated
      with tumor stage, and node and metastatic statuses (p<0.05). Activation of
      Suv39H1 and overexpression of H3K9 tri-methylation may play an important role in
      tumorigenesis. They may be useful as a predictor for poor prognosis in gastric
      carcinoma. Silencing of the Suv39H1 gene decreased tri-methylated H3K9 and
      increased histone H3 acetylation, which caused activation of gene transcription,
      while there was no change in histone H4 acetylation. Depletion of Suv39H1 induced
      apoptosis and inhibited cell proliferation in the gastric cancer MGC803 cell
      line, while decreasing BCL-2, pro-caspase-9, pro-caspase-3 and C-myc. Suv39H1 may
      be a potential gene target for anti-gastric carcinoma therapy. 

PMID- 24737086
TI  - Association of lung function genes with chronic obstructive pulmonary disease.
AB  - BACKGROUND: Spirometric measurements of pulmonary function are important in
      diagnosing and determining the severity of chronic obstructive pulmonary disease
      (COPD). We performed this study to determine whether candidate genes identified
      in genome-wide association studies of spirometric measurements were associated
      with COPD and if they interacted with smoking intensity. METHODS: The current
      analysis included 1,000 COPD subjects and 1,000 controls recruited from 24
      hospital-based pulmonary clinics. Thirteen SNPs, chosen based on genome-wide
      association studies of spirometric measurements in the Korean population cohorts,
      were genotyped. Genetic association tests were performed, adjusting for age, sex,
      and smoking intensity, using models including a SNP-by-smoking interaction term.
      RESULTS: PID1 and FAM13A were significantly associated with COPD susceptibility.
      There were also significant interactions between SNPs in ACN9 and FAM13A and
      smoking pack-years, and an association of ACN9 with COPD in the lowest smoking
      tertile. The risk allele of FAM13A was associated with increased expression of
      FAM13A in the lung. CONCLUSIONS: We have validated associations of FAM13A and
      PID1 with COPD. ACN9 showed significant interaction with smoking and is a
      potential candidate gene for COPD. Significant associations of genetic variants
      of FAM13A with gene expression levels suggest that the associated loci may act as
      genetic regulatory elements for FAM13A gene expression.

PMID- 24737087
TI  - The development and implementation of an outcomes database for imaging-guided
      therapeutic musculoskeletal injections.
AB  - OBJECTIVES: To present the process of creating an imaging-guided injections
      outcomes database and to reflect on how this database has affected the scientific
      activities of the radiology department. MATERIALS AND METHODS: The literature was
      searched to identify studies on the effectiveness of musculoskeletal therapeutic
      injections, areas where research is lacking, and relevant outcome measures.
      Validated outcome measures were chosen and tested in a pilot study. Data
      collection time points of 1 day, 1 week and 1 month post-injection were
      determined and the post-pilot study postal questionnaires were created. The data
      collection process began and has been ongoing for over 4 years. Critical
      reflection on the process and outcomes from the database occurred. RESULTS: The 9
      steps to creating this outcomes database are presented. The numerical rating
      scale for pain (NRS) and the Patient's Global Impression of Change (PGIC) were
      identified as the most valid, reliable, and time-effective outcome measures. At
      most, 50% of patients return their postal questionnaire. The database has
      facilitated the publication of numerous research projects. CONCLUSIONS: Setting
      up an outcomes database is straightforward and productive. The NRS and PGIC were
      considered the most useful outcome measures. This database facilitated critical
      reflection on current practice and provides the foundation for several research
      studies.

PMID- 24737089
TI  - Prenatal education: timing it right.

PMID- 24737088
TI  - Optimization of fully aligned bioactive electrospun fibers for "in vitro" nerve
      guidance.
AB  - Complex architecture of natural tissues such as nerves requires the use of
      multifunctional scaffolds with peculiar topological and biochemical signals able
      to address cell behavior towards specific events at the cellular (microscale) and
      macromolecular (nanoscale) level. In this context, the electrospinning technique
      is useful to generate fiber assemblies having peculiar fiber diameters at the
      nanoscale and patterned by unidirectional ways, to facilitate neurite extension
      via contact guidance. Following a bio-mimetic approach, fully aligned
      polycaprolactone fibers blended with gelatin macromolecules have been fabricated
      as potential bioactive substrate for nerve regeneration. Morphological and
      topographic aspects of electrospun fibers assessed by SEM/AFM microscopy
      supported by image analyses elaboration allow estimating an increase of fully
      aligned fibers from 5 to 39% as collector rotating rate increases from 1,000 to
      3,000 rpm. We verify that fully alignment of fibers positively influences in
      vitro response of hMSC and PC-12 cells in neurogenic way. Immunostaining images
      show that the presence of topological defects, i.e., kinks--due to more frequent
      fiber crossing--in the case of randomly organized fiber assembly concurs to
      interfere with proper neurite outgrowth. On the contrary, fully aligned fibers
      without kinks offer a more efficient contact guidance to direct the orientation
      of nerve cells along the fibers respect to randomly organized ones, promoting a
      high elongation of neurites at 7 days and the formation of bipolar extensions.
      So, this confirms that the topological cue of fully alignment of fibers elicits a
      favorable environment for nerve regeneration.

PMID- 24737090
TI  - Risk factors for delayed lactogenesis among women with gestational diabetes
      mellitus.

PMID- 24737091
TI  - Formula sample distribution in US baby-friendly hospitals.

PMID- 24737092
TI  - Letter to the editor regarding "donor human milk bank data collection in North
      America: an assessment of current status and future needs" from the human milk
      banking association of North America.

PMID- 24737093
TI  - Authors' response to "a letter to the editor regarding 'donor human milk bank
      data collection in north america: an assessment of current status and future
      needs' from the human milk banking association of north america".

PMID- 24737094
TI  - My baby has tongue-tie: what does this mean?

PMID- 24737096
TI  - The ALDB box: automatic testing of cognitive performance in groups of aviary
      housed pigeons.
AB  - The combination of highly controlled experimental testing and the voluntary
      participation of unrestrained animals has many advantages over traditional,
      laboratory-based learning environments in terms of animal welfare, learning
      speed, and resource economy. Such automatic learning environments have recently
      been developed for primates (Fagot & Bonte, 2010; Fagot & Paleressompoulle,
      2009;) but, so far, has not been achieved with highly mobile creatures such as
      birds. Here, we present a novel testing environment for pigeons. Living together
      in small groups in outside aviaries, they can freely choose to participate in
      learning experiments by entering and leaving the automatic learning box at any
      time. At the single-access entry, they are individualized using radio frequency
      identification technology and then trained or tested in a stress-free and self
      terminating manner. The voluntary nature of their participation according to
      their individual biorhythm guarantees high motivation levels and good learning
      and test performance. Around-the-clock access allows for massed-trials training,
      which in baboons has been proven to have facilitative effects on discrimination
      learning. The performance of 2 pigeons confirmed the advantages of the automatic
      learning device for birds box. The latter is the result of a development process
      of several years that required us to deal with and overcome a number of technical
      challenges: (1) mechanically controlled access to the box, (2) identification of
      the birds, (3) the release of a bird and, at the same time, prevention of others
      from entering the box, and (4) reliable functioning of the device despite long
      operation times and exposure to high dust loads and low temperatures. 

PMID- 24737097
TI  - WeaVR: a self-contained and wearable immersive virtual environment simulation
      system.
AB  - We describe WeaVR, a computer simulation system that takes virtual reality
      technology beyond specialized laboratories and research sites and makes it
      available in any open space, such as a gymnasium or a public park. Novel hardware
      and software systems enable HMD-based immersive virtual reality simulations to be
      conducted in any arbitrary location, with no external infrastructure and little
      to-no setup or site preparation. The ability of the WeaVR system to provide
      realistic motion-tracked navigation for users, to improve the study of large
      scale navigation, and to generate usable behavioral data is shown in three
      demonstrations. First, participants navigated through a full-scale virtual
      grocery store while physically situated in an open grass field. Trajectory data
      are presented for both normal tracking and for tracking during the use of
      redirected walking that constrained users to a predefined area. Second, users
      followed a straight path within a virtual world for distances of up to 2 km while
      walking naturally and being redirected to stay within the field, demonstrating
      the ability of the system to study large-scale navigation by simulating virtual
      worlds that are potentially unlimited in extent. Finally, the portability and
      pedagogical implications of this system were demonstrated by taking it to a
      regional high school for live use by a computer science class on their own school
      campus. 

PMID- 24737098
TI  - The value and cost of complexity in predictive modelling: role of tissue
      anisotropic conductivity and fibre tracts in neuromodulation.
AB  - OBJECTIVES: Computational methods are increasingly used to optimize transcranial
      direct current stimulation (tDCS) dose strategies and yet complexities of
      existing approaches limit their clinical access. Since predictive modelling
      indicates the relevance of subject/pathology based data and hence the need for
      subject specific modelling, the incremental clinical value of increasingly
      complex modelling methods must be balanced against the computational and clinical
      time and costs. For example, the incorporation of multiple tissue layers and
      measured diffusion tensor (DTI) based conductivity estimates increase model
      precision but at the cost of clinical and computational resources. Costs related
      to such complexities aggregate when considering individual optimization and the
      myriad of potential montages. Here, rather than considering if additional details
      change current-flow prediction, we consider when added complexities influence
      clinical decisions. APPROACH: Towards developing quantitative and qualitative
      metrics of value/cost associated with computational model complexity, we
      considered field distributions generated by two 4 * 1 high-definition montages
      (m1 = 4 * 1 HD montage with anode at C3 and m2 = 4 * 1 HD montage with anode at
      C1) and a single conventional (m3 = C3-Fp2) tDCS electrode montage. We evaluated
      statistical methods, including residual error (RE) and relative difference
      measure (RDM), to consider the clinical impact and utility of increased
      complexities, namely the influence of skull, muscle and brain anisotropic
      conductivities in a volume conductor model. MAIN RESULTS: Anisotropy modulated
      current-flow in a montage and region dependent manner. However, significant
      statistical changes, produced within montage by anisotropy, did not change
      qualitative peak and topographic comparisons across montages. Thus for the
      examples analysed, clinical decision on which dose to select would not be altered
      by the omission of anisotropic brain conductivity. SIGNIFICANCE: Results
      illustrate the need to rationally balance the role of model complexity, such as
      anisotropy in detailed current flow analysis versus value in clinical dose
      design. However, when extending our analysis to include axonal polarization, the
      results provide presumably clinically meaningful information. Hence the
      importance of model complexity may be more relevant with cellular level
      predictions of neuromodulation.

PMID- 24737099
TI  - Expression of mammalian target of rapamycin in atherosclerotic plaques is
      decreased under diabetic conditions: a mechanism for rapamycin resistance.
AB  - Our previous study demonstrated that diabetes increases in-stent restenosis
      following rapamycin-eluting stent placement, which was defined as rapamycin
      resistance. However, the underlying mechanisms of rapamycin resistance remain to
      be determined. In the present study, male apolipoprotein E-deficient (ApoE-/-)
      mice were randomly divided into control and diabetic groups. Diabetes was induced
      by injecting streptozocin (STZ). The hyperglycemic state, defined as a fasting
      plasma glucose level >13 mmol/l, was maintained for 8 weeks. At the end of the
      administration, the plasma levels of triglycerides (TG) and total cholesterol
      (TC) were significantly elevated in the diabetic group compared with the control
      mice (all P<0.01). The present study revealed that diabetes increased the
      atherosclerotic plaque size of the aortic root (P<0.01) and the content of
      vascular smooth muscle cells (VSMCs) in the atherosclerotic lesion (P<0.01).
      Furthermore, the protein expression and phosphorylation of mammalian target of
      rapamycin (mTOR), 4E-binding protein 1 and ribosomal S6 kinase 1 (P<0.01) were
      significantly decreased in the diabetic mice compared with the control group. The
      decrease in the expression and phosphorylation of mTOR and its downstream kinases
      may be one of the molecular mechanisms underlying rapamycin resistance.

PMID- 24737100
TI  - Influence of surface treatment on osseointegration of dental implants:
      histological, histomorphometric and radiological analysis in vivo.
AB  - OBJECTIVE: The aim of this article is to compare the influence of surface
      treatment on the integration (at 2, 4 and 8 weeks) of 120 dental implants
      inserted in 60 tibiae of rabbits. MATERIALS AND METHODS: Four different surfaces
      were double-blind tested: blasted, acid-etched and discrete crystal deposition
      (DCD) (group A); blasted (group B); acid-etched (group C) and blasted and acid
      etched (group D). Bone-to-implant contact plus reverse torque and bone level were
      measured at the time of implant insertion and at 14, 28 and 56 days of healing.
      RESULTS: Group A showed the highest early and late bone-to-implant contact (BIC)
      values: 40.8 +/- 2.3 % at 14 days decreasing to 27.7 +/- 1.1 % after 28 days and
      39.4 +/- 1.4 % at 56 days. For group B, the average BIC values at 14, 28 and 56
      days were 23.34 +/- 2.1, 23.77 +/- 1.9 and 29.47 +/- 1.7 %, respectively. Group C
      showed a value of 25.72 +/- 2.3 % after 14 days of integration, 34.92 +/- 2.2 %
      at 28 days and 32.91 +/- 1.6 % at 56 days. Group D showed a BIC value of 32 +/-
      2.5 % at 14 days, 32.85 +/- 1.4 % at 28 days and 34.04 +/- 2.3 % at 56 days. In
      the scanning electron microscopy (SEM) analysis, no statistically significant
      differences were found. The Ca/P ratio values were 1.762 for surface A, 1.625 for
      surface B, 1.663 for surface C and finally 1.722 for surface D. CONCLUSIONS:
      Therefore, we conclude that even if there seems to be a tendency to obtain better
      BIC results with surface A (blasted-etched and covered with hydroxyapatite (HA)),
      no statistical differences were obtained in this study. CLINICAL RELEVANCE: The
      study shows the influence of different implant surfaces in increasing
      osseointegation for immediate loading implants.

PMID- 24737101
TI  - A micro-computed tomography study of the relationship between radicular grooves
      and root canal morphology in mandibular first premolars.
AB  - OBJECTIVES: This study aims to explore the correlation between radicular grooves
      and root canal types by quantitatively detecting the radicular groove of
      mandibular first premolars using micro-computed tomography. MATERIALS AND
      METHODS: A total of 127 mandibular first premolars were scanned by micro-computed
      tomography, and 52 teeth with radicular grooves were identified. Details of root
      canal type and groove length, depth, and location were analyzed from three
      dimensional images. RESULTS: A total of 40.9 % (52/127) of teeth had radicular
      grooves. Most of the grooves (69.5 %) were located on the mesial surface of the
      root. The prevalence of radicular grooves in single canals (17.4 %; 15/86) was
      lower than that in multiple and complex canals (90.2 %; 37/41); this difference
      was statistically significant (P < 0.001). The mean length and depth of radicular
      groove in type V (7.7 +/- 2.16 and 0.87 +/- 0.39 mm, respectively) and other
      types of canals (6.91 +/- 2.67 and 0.63 +/- 0.27 mm, respectively) were
      significantly longer and deeper than type I canals (6.06 +/- 2.12 and 0.43 +/-
      0.14 mm, respectively). CONCLUSIONS: Multiple and complex canals had a higher
      incidence of radicular grooves and more complicated root morphology than single
      and simple canals. Therefore, the anatomy of radicular grooves may influence root
      canal morphology. CLINICAL RELEVANCE: The existence of a radicular groove is
      closely related to root anatomy and root canal morphology. Anatomical complexity
      increases the difficulty of root canal treatment and periodontal therapy;
      therefore, the current data may provide clinicians with a more thorough
      understanding of the relationship between radicular grooves and root canal
      morphology.

PMID- 24737102
TI  - Oncocytic lipoadenoma of the salivary gland: a clinicopathologic analysis of 7
      cases and review of the literature.
AB  - Oncocytic lipoadenoma is an exceedingly uncommon neoplasm of the salivary gland
      composed of oncocytic epithelium and adipose tissue. Retrospective. Seven cases
      of oncocytic lipoadenoma were analyzed in order to further characterize the
      clinical and pathologic features of this rare tumor. The patients included six
      males and one female who ranged from 40 to 83 years of age (mean 62 years) at
      presentation. All tumors arose in the parotid gland. Grossly, the tumors were
      solitary, well circumscribed and had light brown to yellow cut surfaces.
      Histologically, the tumors were composed of an admixed population of oncocytes
      and adipocytes in varying proportions, with the lipomatous component ranging from
      5 to 70 %. Other common features included the presence of serous acini, ductal
      elements, sebaceous glands, and a patchy chronic inflammation. Clinical follow up
      information, available in all cases, with a duration of 3-148 months (mean 57
      months), showed no evidence of tumor recurrence. Due to its rarity, oncocytic
      lipoadenoma can pose problems in diagnosis, although the distinctive morphologic
      features of this neoplasm allow for separation from more commonly recognized
      oncocytic neoplasms of the salivary glands.

PMID- 24737103
TI  - Multiple orthokeratinized odontogenic cysts: a case report.
AB  - The purpose of this report is to document the clinical, radiographic,
      pathological and molecular findings of the first case of multiple
      orthokeratinized odontogenic cysts (OOCs). Multiple odontogenic keratocysts are
      one of the major features of nevoid basal cell carcinoma syndrome (NBCCS), and
      loss of heterozygosity in the PTCH gene, the culprit gene for NBCCS, has recently
      been found in sporadic OOC cases. Therefore, in this presenting case, we also
      investigated the possibility that this patient might also have NBCCS, by
      comparing the available clinical information and the molecular findings of this
      case to the diagnostic criteria for NBCCS (as proposed by the First International
      Colloquium on NBCCS in 2011). However, this patient with multiple OOCs showed no
      evidence of having NBCCS. This conclusion supports the findings from previous
      case series based on sporadic cases that OOC does not appear to be associated
      with NBCCS. 

PMID- 24737104
TI  - Induced redox responsiveness and electroactivity for altering the properties of
      micelles without external stimuli.
AB  - Control over micelle properties is vital in the field of drug delivery, and the
      ability to modify these properties in order to trigger dissociation is highly
      desirable. We prepared polymeric micelles with the ability to undergo
      dissociation over time without the need for external stimulation by incorporating
      an electroactive and redox responsive segment into amphiphilic copolymers. The
      incorporation of this segment also provides the ability to tailor the critical
      micelle concentration (CMC) and micelle size of the copolymers. Amphiphilic PEG
      PLA copolymers were functionalized by coupling to an aniline pentamer in two
      different oxidation states (leucoemeraldine and emeraldine state). The
      incorporation of the electroactive and redox responsive aniline pentamer
      decreased the CMCs and the micelle size, independent of the oxidation state.
      However, the copolymers with the aniline pentamer in the leucoemeraldine state
      had significantly lower CMCs than the copolymers with the aniline pentamer in the
      emeraldine state. Simultaneously, stability tests performed on the functionalized
      micelles demonstrated the oxidation of the aniline segment, from the
      leucoemeraldine to the emeraldine state, over time. The oxidation led to an
      increase in the CMC, and the copolymers could thereby represent an excellent
      starting point for triggering drug release without external stimuli. 

PMID- 24737105
TI  - [Update: standardized CT/HRCT classification of occupational and environmental
      thoracic diseases in Germany].
AB  - The high-resolution computed tomography (HRCT) coding scheme of the international
      classification of occupational and environmental respiratory diseases (ICOERD)
      presented here is an instrument for a standardized semiquantitative description
      of occupation and environment-linked as well as other pulmonary and pleural
      diseases. Analogous to the International Labour Organization (ILO)
      classification, the ICOERD coding scheme should always be used when the CT/HRCT
      examination is employed for occupational medical investigations or expert
      opinions. After publication of the guidelines and recommendations on diagnostics
      and expert assessment of asbestos-linked diseases and silicosis, the application
      of a standardized investigation program and assessment with the ICOERD
      classification form are obligatory, at least for the initial assessment.
      Furthermore, its use in the field of follow-up assessments of occupational
      diseases should be encouraged in order to guarantee comparability between
      individual reports (interreader variability) and at least a semiquantitative
      assessment of disease progression in isolated cases. Because the anatomical
      structures in projection radiography and CT are not presented identically, a 1:1
      transfer of the results of the ILO classification to the CT/HRCT coding scheme is
      not possible. An overview image of the thorax does not allow overlap-free
      reproduction of structures, in contrast to CT. These methodological differences
      can in cases of isolated assessment result in different opinions of projection
      and CT images mostly by different investigators. In cases of discrepant opinions
      an integrated report of findings by combination of all information from both
      procedures is necessary. 

PMID- 24737106
TI  - Strontium ranelate stimulates the activity of bone-specific alkaline phosphatase:
      interaction with Zn(2+) and Mg (2+).
AB  - Strontium ranelate (SR) is an orally administered and bone-targeting anti
      osteoporotic agent that increases osteoblast-mediated bone formation while
      decreasing osteoclastic bone resorption, and thus reduces the risk of vertebral
      and femoral bone fractures in postmenopausal women with osteoporosis.
      Osteoblastic alkaline phosphatase (ALP) is a key enzyme involved in the process
      of bone formation and osteoid mineralization. In this study we investigated the
      direct effect of strontium (SR and SrCl2) on the activity of ALP obtained from
      UMR106 osteosarcoma cells, as well as its possible interactions with the divalent
      cations Zn(2+) and Mg(2+). In the presence of Mg(2+), both SR and SrCl2 (0.05-0.5
      mM) significantly increased ALP activity (15-66 % above basal), and this was dose
      dependent in the case of SR. The stimulatory effect of strontium disappeared in
      the absence of Mg(2+). The cofactor Zn(2+) also increased ALP activity (an effect
      that reached a plateau at 2 mM), and co-incubation of 2 mM Zn(2+) with 0.05-0.5
      mM SR showed an additive effect on ALP activity stimulation. SR induced a dose
      dependent decrease in the Km of ALP (and thus an increase in affinity for its
      substrate) with a maximal effect at 0.1 mM. Co-incubation with 2 mM Zn(2+)
      further decreased Km in all cases. These direct effects of SR on osteoblastic ALP
      activity could be indicating an alternative mechanism by which this compound may
      regulate bone matrix mineralization.

PMID- 24737107
TI  - TLR-mediated STAT3 and ERK activation controls IL-10 secretion by human B cells.
AB  - IL-10-producing B cells have a regulatory effect in various mouse models for
      immune-mediated disorders via secretion of IL-10, a potent immunoregulatory
      cytokine. However, currently, the signaling pathways that regulate IL-10
      production in B cells are not well understood. Here, we show that TLR signaling,
      but not BCR activation or CD40 ligation, induces potent production of IL-10 in
      human B cells. We demonstrate that the activation of STAT3 and ERK is required
      for TLR-induced IL-10 production by B cells, since inhibition of STAT3 or ERK
      activation abrogates TLR-induced IL-10 production. We also uncover a novel
      function of the TLR-MyD88-STAT3 pathway in B cells, namely controlling IL-10
      production, in addition to the known role for this pathway in antibody
      production. Furthermore, IFN-alpha, a member of the type I IFN family,
      differentially modulates TLR7/8- and TLR9-activated STAT3 and ERK in B cells,
      which provides an explanation for our findings that IFN-alpha enhances TLR7/8
      induced, but not TLR9-induced IL-10 production. These results yield insights into
      the mechanisms by which TLR signaling regulates IL-10 production in B cells and
      how type I IFN modulates TLR-mediated IL-10 production by B cells, therefore
      providing potential targets to modulate the function of IL-10-producing B cells. 

PMID- 24737108
TI  - Fixed-dose combination therapy for the prevention of cardiovascular disease.
AB  - BACKGROUND: Cardiovascular disease (CVD) is the leading cause of death and
      disability worldwide, yet CVD risk factor control and secondary prevention rates
      remain low. A fixed-dose combination of blood pressure and cholesterol lowering
      and antiplatelet treatments into a single pill, or polypill, has been proposed as
      one strategy to reduce the global burden of CVD by up to 80% given its potential
      for better adherence and lower costs. OBJECTIVES: To determine the effectiveness
      of fixed-dose combination therapy on reducing fatal and non-fatal CVD events and
      on improving blood pressure and lipid CVD risk factors for both primary and
      secondary prevention of CVD. We also aimed to determine discontinuation rates,
      adverse events, health-related quality of life, and costs of fixed-dose
      combination therapy. SEARCH METHODS: We searched the Cochrane Central Register of
      Controlled Trials (CENTRAL) in The Cochrane Library (2013, Issue 6), MEDLINE Ovid
      (1946 to week 2 July 2013), EMBASE Ovid (1980 to Week 28 2013), ISI Web of
      Science (1970 to 19 July 2013), and the Database of Abstracts of Reviews of
      Effects (DARE), Health Technology Assessment Database (HTA), and Health Economics
      Evaluations Database (HEED) (2011, Issue 4) in The Cochrane Library. We used no
      language restrictions. SELECTION CRITERIA: We included randomised controlled
      trials of a fixed-dose combination therapy including at least one blood pressure
      lowering and one lipid lowering component versus usual care, placebo, or a single
      drug active component for any treatment duration in adults >= 18 years old with
      no restrictions on presence or absence of pre-existing cardiovascular disease.
      DATA COLLECTION AND ANALYSIS: Three review authors independently selected studies
      for inclusion and extracted the data. We evaluated risk of bias using the
      Cochrane risk of bias assessment tool. We sought to include outcome data on all
      cause mortality, fatal and non-fatal CVD events, adverse events, changes in
      systolic and diastolic blood pressure, total and low density lipoprotein (LDL)
      cholesterol concentrations, discontinuation rates, quality of life, and costs. We
      calculated risk ratios (RR) for dichotomous data and weighted mean differences
      (MD) for continuous data with 95% confidence intervals (CI) using fixed-effect
      models when heterogeneity was low (I(2) < 50%) and random-effects models when
      heterogeneity was high (I(2) > 50%). MAIN RESULTS: We found nine randomised
      controlled trials with a total of 7047 participants. Seven of the nine trials
      evaluated the effects of fixed-dose combination therapy on primary CVD
      prevention, and the trial length ranged from six weeks to 15 months. We found a
      moderate to high risk of bias in the domains of selection, performance,
      detection, attrition, and other types of bias in five of the nine trials.
      Compared with the comparator groups, the effects of the fixed-dose combination
      treatment on mortality (1.2% versus 1.0%, RR 1.26, 95% CI 0.67 to 2.38,  N =
      3465) and cardiovascular events (4.0% versus 2.9%, RR 1.38, 95% CI 0.91 to 2.10,
      N = 2479) were uncertain (low quality evidence). The low event rates for these
      outcomes, limited availability of data as only two out of nine trials reported on
      these outcomes, and a high risk of bias in at least one domain suggest that these
      results should not be viewed with confidence. Adverse events were common in both
      the intervention (30%) and comparator (24%) groups, with participants randomised
      to fixed-dose combination therapy being 20% (95% CI 9% to 30%) more likely to
      report an adverse event. Notably, no serious adverse events were reported.
      Compared with placebo, the rate of discontinuation among participants randomised
      to fixed-dose combination was higher (14% versus 11%, RR 1.26 95% CI 1.02 to
      1.55). The weighted mean differences in systolic and diastolic blood pressure
      between the intervention and control arms were -7.05 mmHg (95% CI -10.18 to 
      3.87) and -3.65 mmHg (95% CI -5.44 to -1.85), respectively. The weighted mean
      differences (95% CI) in total and LDL cholesterol between the intervention and
      control arms were -0.75 mmol/L (95% CI -1.05 to -0.46) and -0.81 mmol/L (95% CI 
      1.09 to -0.53), respectively. There was a high degree of statistical
      heterogeneity in comparisons of blood pressure and lipids (I(2) >= 70% for all)
      that could not be explained, so these results should be viewed with caution.
      Fixed-dose combination therapy improved adherence to a multi-drug strategy by 33%
      (26% to 41%) compared with usual care, but this comparison was reported in only
      one study. The effects of fixed-dose combination therapy on quality of life are
      uncertain, though these results were reported in only one trial. No trials
      reported costs. AUTHORS' CONCLUSIONS: Compared with placebo, single drug active
      component, or usual care, the effects of fixed-dose combination therapy on all
      cause mortality or CVD events are uncertain; only few trials report these
      outcomes and the included trials were primarily designed to observe changes in
      CVD risk factor levels rather than clinical events. Reductions in blood pressure
      and lipid parameters are generally lower than those previously projected, though
      substantial heterogeneity of results exists. Fixed-dose combination therapy is
      associated with modest increases in adverse events compared with placebo, single
      drug active component, or usual care but may be associated with improved
      adherence to a multidrug regimen. Ongoing trials of fixed-dose combination
      therapy will likely inform key outcomes.

PMID- 24737110
TI  - Psychosocial impact of cancer cachexia.
AB  - BACKGROUND: Cancer cachexia has impact on patients and their family members.
      Patients experience loss of weight often accompanied by anorexia and other
      debilitating symptoms that have clinical impact and impact everyday life. The
      importance of understanding this impact lies in (1) the alleviation of cachexia
      related suffering and (2) its implications for treating cachexia. REVIEW: Two
      decades of exploratory investigation of the manifestations, meaning and
      management of cancer cachexia reveal emotional and social impacts for both
      patients and their carers. Patients can describe change in appearance and loss of
      physical strength often accompanied by change in eating habits (amount, type and
      pattern of food intake). The psychosocial effects can include loss of
      independence, sense of failure, sense of helplessness, conflict with family
      members over food, social isolation and thoughts of death. They are effects that
      can distress. Conversely, weight loss, especially early in its course and for
      those who are obese, can be perceived as beneficial, which inhibits self
      management of diet and physical activity. CONCLUSION: Models of the psychosocial
      effects of cancer cachexia have been developed, leading to, as yet unproven,
      propositions of how negative patient and family impacts can be addressed. This
      literature overlooks the potential importance of psychosocial intervention to
      emerging multimodal treatments for the multicausal syndrome. Psychosocial
      intervention in cachexia should be tested for potential to help people affected
      by cancer cachexia feel better but also for potential to make people better by
      aiding uptake and compliance with multimodal therapy.

PMID- 24737109
TI  - Intraoperative visualization of cerebral oxygenation using hyperspectral image
      data: a two-dimensional mapping method.
AB  - PURPOSE: Superficial temporal artery (STA)-middle cerebral artery (MCA) bypass is
      an important technique for cerebrovascular reconstruction. Intraoperative
      hemodynamic imaging is needed to perform cerebrovascular reconstruction safely
      and effectively. Optical intrinsic signal (OIS) imaging is commonly used for
      assessing cerebral hemodynamics in experimental studies, because it can provide
      high-resolution mapping images. However, OIS is not used clinically due to
      algorithm, instrumentation and spectral resolution limitations. We tested the
      feasibility of a hyperspectral camera (HSC) for assessment of cortical
      hemodynamics with spectral imaging of the cerebral cortex in rats and in vivo
      humans. METHODS: A hyperspectral camera (HSC) was tested in a rat model of
      cerebral ischemia (middle cerebral artery occlusion) and during human
      revascularization surgery (STA-MCA anastomosis). Changes in cortical oxygen
      saturation were derived from spectral imaging data (400-800 nm) collected by
      exposing the cortex to Xenon light. Reflected light was sampled using the HSC.
      The system was then tested intraoperatively during superficial temporal artery to
      middle cerebral artery anastomosis procedures. Comparison with single-photon
      emission computed tomography (SPECT) imaging data was done. RESULTS: During
      middle cerebral artery occlusion in rats, the HSC technique showed a significant
      decrease in cortical oxygen saturation in the ischemic hemisphere. In clinical
      cases, the cortical oxygen saturation was increased after STA-MCA anastomosis,
      which agreed with the SPECT imaging data. CONCLUSION: Continuous collection of
      imaging spectroscopic data is feasible and may provide reliable quantification of
      the hemodynamic responses in the brain. The HSC system may be useful for
      monitoring intraoperative changes in cortical surface hemodynamics during
      revascularization procedures in humans.

PMID- 24737111
TI  - Identifying recreational physical activities associated with muscle quality in
      men and women aged 50 years and over.
AB  - BACKGROUND: Several studies conducted in a laboratory-related environment have
      shown that exercise is associated with increased muscle quality in older adults.
      The aim of the present study was to investigate whether recreational exercise may
      also be associated with muscle quality in men and women aged 50 years and over.
      METHODS: Data are from 312 individuals (215 women) aged 50 years and older. Body
      composition (dual-energy X-ray absorptiometry) and knee extension strength (KES)
      of the right leg (one repetition maximum) were assessed. Muscle quality (MQ)
      (KES/right lower limb lean mass) was calculated. Recreational exercises (duration
      and weekly amount) were determined by structured interview. RESULTS: The duration
      of the period during which participants practiced resistance activities was the
      only predictor of MQ (p = 0.018) and explained an additional 1.6 % of the
      variance in MQ, after controlling for age and gender. Furthermore, the weekly
      amount of practice of aerobic activities significantly interacted with age (p <
      0.001) to determine MQ. CONCLUSIONS: Findings suggest that long-term engagement
      in resistance exercise is beneficial for muscle quality and should be encouraged.
      Furthermore, beyond 60 years, aerobic activities also seem to be positively
      associated with muscle quality.

PMID- 24737112
TI  - Assessing sarcopenic prevalence and risk factors in residential aged care:
      methodology and feasibility.
AB  - BACKGROUND: Sarcopenia is a significant geriatric syndrome with both health care
      expenditure and personal burden. Most recently, the European Working Group in
      Sarcopenia in Older Adults has established a consensus definition and assessment
      criteria for sarcopenia that includes a below-normal muscle mass and muscle
      function (either or both of below-normal muscle strength and physical
      performance). Using these criteria, work is needed to identify the prevalence and
      risk factors among the old, and those most susceptible to sarcopenia, the very
      old. This manuscript describes the recruitment and data collection methodology,
      and direct burden to participants, among a very old cohort residing in a
      residential aged care (RAC) setting. METHODS: Eleven RAC facilities participated
      in the study. Potential participants were identified by the facility service
      manager and then randomised into the study. All participants gave self or
      substitute decision maker consent. Participants undertook a single one on one
      assessment that included measures of sarcopenia, functional capacity, cognitive
      and nutritional health, falls, activity, facility and hospital history, physical
      activity and assessment burden. A sub-study of physical activity and sedentary
      behaviours measured by activPAL3TM inclinometer was also conducted. RESULTS: Of
      709 residents, 328 were ineligible to participate. Two hundred and seventy-three
      residents were randomised to the study and 102 gave informed or substitute
      decision maker consent. Participants were 84.5 +/- 8.2 years of age and had been
      in care for 1,204.2 +/- 1,220.1 days. The groups need for care was high (Aged
      Care Funding Instrument score of 2.6 +/- 1.7) and they had a below-normal
      functional (Short Physical Performance Battery summery score of 3.5 +/- 2.4). The
      larger percentage of participants had no depression and normal cognitive
      capacity. A total of 33 residents participated in the activPAL study. Each
      assessment took an average of 27.0 +/- 7.0 min, with a low assessment burden
      reported by participants. CONCLUSIONS: The successful assessment of sarcopenia
      and physical activity in a RAC setting is labour intensive to establish, but
      feasible to conduct. Low recruitment numbers and the restrictive exclusion
      criteria, may have limited the accuracy of this work. However, this work is a
      primary step in establishing the level of sarcopenia and its risk factors for
      those in end-of-life care.

PMID- 24737113
TI  - Two-dimensional assembly based on flow supramolecular chemistry: kinetic control
      of molecular interactions under solvent diffusion.
AB  - Self-assembly of porphyrin molecules can be controlled kinetically to form
      structures with lengths extending from the nano- to the micrometer scale, through
      a programmed solvent-diffusion process in designed microflow spaces. Temporal
      solvent structures generated in the microflow were successfully transcribed into
      molecular architectures. 

PMID- 24737114
TI  - Clinical evaluation of BrainTree, a motor imagery hybrid BCI speller.
AB  - OBJECTIVE: While brain-computer interfaces (BCIs) for communication have reached
      considerable technical maturity, there is still a great need for state-of-the-art
      evaluation by the end-users outside laboratory environments. To achieve this
      primary objective, it is necessary to augment a BCI with a series of components
      that allow end-users to type text effectively. APPROACH: This work presents the
      clinical evaluation of a motor imagery (MI) BCI text-speller, called BrainTree,
      by six severely disabled end-users and ten able-bodied users. Additionally, we
      define a generic model of code-based BCI applications, which serves as an
      analytical tool for evaluation and design. MAIN RESULTS: We show that all users
      achieved remarkable usability and efficiency outcomes in spelling. Furthermore,
      our model-based analysis highlights the added value of human-computer interaction
      techniques and hybrid BCI error-handling mechanisms, and reveals the effects of
      BCI performances on usability and efficiency in code-based applications.
      SIGNIFICANCE: This study demonstrates the usability potential of code-based MI
      spellers, with BrainTree being the first to be evaluated by a substantial number
      of end-users, establishing them as a viable, competitive alternative to other
      popular BCI spellers. Another major outcome of our model-based analysis is the
      derivation of a 80% minimum command accuracy requirement for successful code
      based application control, revising upwards previous estimates attempted in the
      literature.

PMID- 24737115
TI  - PET imaging reveals brain functional changes in internet gaming disorder.
AB  - BACKGROUND: Internet gaming disorder is an increasing problem worldwide,
      resulting in critical academic, social, and occupational impairment. However, the
      neurobiological mechanism of internet gaming disorder remains unknown. The aim of
      this study is to assess brain dopamine D2 (D2)/Serotonin 2A (5-HT2A) receptor
      function and glucose metabolism in the same subjects by positron emission
      tomography (PET) imaging approach, and investigate whether the correlation exists
      between D2 receptor and glucose metabolism. METHODS: Twelve drug-naive adult
      males who met criteria for internet gaming disorder and 14 matched controls were
      studied with PET and (11)C-N-methylspiperone ((11)C-NMSP) to assess the
      availability of D2/5-HT2A receptors and with (18)F-fluoro-D-glucose ((18)F-FDG)
      to assess regional brain glucose metabolism, a marker of brain function. (11)C
      NMSP and (18)F-FDG PET imaging data were acquired in the same individuals under
      both resting and internet gaming task states. RESULTS: In internet gaming
      disorder subjects, a significant decrease in glucose metabolism was observed in
      the prefrontal, temporal, and limbic systems. Dysregulation of D2 receptors was
      observed in the striatum, and was correlated to years of overuse. A low level of
      D2 receptors in the striatum was significantly associated with decreased glucose
      metabolism in the orbitofrontal cortex. CONCLUSIONS: For the first time, we
      report the evidence that D2 receptor level is significantly associated with
      glucose metabolism in the same individuals with internet gaming disorder, which
      indicates that D2/5-HT2A receptor-mediated dysregulation of the orbitofrontal
      cortex could underlie a mechanism for loss of control and compulsive behavior in
      internet gaming disorder subjects.

PMID- 24737116
TI  - Cushingoid facies on (18)F-FDG PET/CT.

PMID- 24737118
TI  - From Homo sapiens to Homo in nexu (connected man): could functional imaging
      redefine the brain of a "new human species"?

PMID- 24737117
TI  - In vivo and in vitro evidence that 99mTc-HYNIC-interleukin-2 is able to detect T
      lymphocytes in vulnerable atherosclerotic plaques of the carotid artery.
AB  - PURPOSE: Recent advances in basic science have established that inflammation
      plays a pivotal role in the pathogenesis of atherosclerosis. Inflammatory cells
      are thought to be responsible for the transformation of a stable plaque into a
      vulnerable one. Lymphocytes constitute at least 20 % of infiltrating cells in
      these vulnerable plaques. Therefore, the interleukin-2 (IL-2) receptor, being
      overexpressed on activated T lymphocytes, may represent an attractive biomarker
      for plaque vulnerability. The aim of this study was to evaluate the specificity
      of radiolabelled IL-2 [(99m)Tc-hydrazinonicotinamide (HYNIC)-IL-2] for imaging
      the lymphocytic infiltration in carotid plaques in vivo by planar and single
      photon emission computed tomography (SPECT)/CT imaging and ex vivo by microSPECT
      and autoradiography. METHODS: For the in vivo study, ten symptomatic patients
      with advanced plaques at ultrasound who were scheduled for carotid endarterectomy
      underwent (99m)Tc-HYNIC-IL-2 scintigraphy. The images were analysed visually on
      planar and SPECT images and semi-quantitatively on SPECT images by calculating
      target to background (T/B) ratios. After endarterectomy, immunomorphological
      evaluation and immunophenotyping were performed on plaque slices. For the ex vivo
      studies, four additional patients were included and, after in vitro incubation of
      removed plaques with (99m)Tc-HYNIC-IL-2, autoradiography was performed and
      microSPECT images were acquired. RESULTS: Visual analysis defined clear (99m)Tc
      HYNIC-IL-2 uptake in seven of the ten symptomatic plaques. SPECT/CT allowed
      visualization in eight of ten. A significant correlation was found between the
      number of CD25+ lymphocytes and the total number of CD25+ cells in the plaque and
      the T/B ratio with adjacent carotid artery as background (Pearson's r = 0.89, p =
      0.003 and r = 0.87, p = 0.005, respectively). MicroSPECT imaging showed clear
      (99m)Tc-HYNIC-IL-2 uptake within the plaque wall and not in the lipidic core.
      With autoradiography, only CD3+ lymphocytes were found to be labelled.
      CONCLUSION: These in vivo and ex vivo studies confirm the specificity of (99m)Tc
      HYNIC-IL-2 for imaging activated T lymphocytes in carotid plaques. (99m)Tc-HYNIC
      IL-2 is a true marker for the inflamed plaque and therefore of plaque
      instability.

PMID- 24737119
TI  - Application of two-dimensional electrophoresis and mass spectrometry to screen
      endometriosis-related proteins.
AB  - The aim of the present study was to detect the differences in the protein
      expression between Uyghur females with or without endometriosis (EM). The two
      dimensional (2D) gel images of proteins extracted from the serum of Uyghur and
      Han females with EM and the controls were analyzed using Phoretix 2D software,
      and the differentially expressed proteins were identified primarily by database
      query. Having compared the reproducible 2D gel images of proteins from the serum
      of Uihgur and Han females with and without EM, 13 differentially expressed
      proteins were obtained from Uyghur females and eight differentially expressed
      proteins were obtained from Han females. The present study demonstrated ethnic
      differences in gene and protein expression between Uyghur and Han females with
      EM. 

PMID- 24737120
TI  - In reference to preapproval of sinus computed tomography for otolaryngologic
      evaluation of chronic rhinosinusitis does not save health care costs.

PMID- 24737121
TI  - Impact of Mucin1 knockdown on the phenotypic characteristics of the human
      hepatocellular carcinoma cell line SMMC-7721.
AB  - Mucin1 (MUC1) is a transmembrane glycoprotein that plays a key role as an
      oncogene in the tumorigenesis of many human adenocarcinomas. However, the role of
      MUC1 in human hepatocellular carcinoma (HCC) progression remains unclear. In the
      present study, we silenced MUC1 to investigate its effect on the human HCC cell
      line SMMC-7721 and found that knockdown of MUC1 significantly inhibited cell
      proliferation, enhanced cell-cell aggregation and induced apoptosis. No
      significant differences were found in in vitro migration or invasion. We also
      observed that knockdown of MUC1 decreased the translocation of beta-catenin to
      the nucleus, reduced the activity of T cell factor and blocked the expression of
      cyclin D1 and c-Myc. In addition, MUC1 knockdown enhanced the expression of E
      cadherin, a molecular chaperone of beta-catenin that plays an important role in
      cell-cell aggregation. In vivo assays demonstrated that there was no tumor growth
      in mice injected with MUC1-silenced cells. Global gene expression analysis showed
      that a series of genes encoding molecules in the Wnt/beta-catenin, nuclear factor
      kappaB (NF-kappaB), mitogen-activated protein kinase (MAPK), insulin,
      transforming growth factor beta (TGF-beta) and vascular endothelial growth factor
      (VEGF) signaling pathways were all influenced by the knockdown of MUC1, and these
      may contribute to the phenotypic alterations observed. Collectively, our results
      indicate that MUC1 plays a key role in HCC tumorigenesis. 

PMID- 24737123
TI  - The Pressure-Activation-Stress scale in relation to ADHD and cortisol.
AB  - The Pressure-Activation-Stress (PAS) scale is a self-report questionnaire for
      children concerning perceived stress. To explore behavioral and physiological
      correlates, we investigated if scores discriminate between a group prone to
      perceive high levels of stress [children with attention-deficit/hyperactivity
      disorder (ADHD)] and a healthy school sample, and if they are associated with
      diurnal cortisol levels. The PAS scale was filled in at home by children (11-17
      years) with clinically confirmed ADHD (n = 102) and non-affected comparisons (n =
      146). Saliva samples were collected four times during a regular school day for
      radioimmunoassay analysis of cortisol. Subtypes and severity of ADHD symptoms
      were determined using parental rating scales. Children with ADHD scored higher on
      the PAS scale than a school sample. The PAS scores were similar over ages in the
      ADHD group while they increased with age in the healthy group. Female sex was
      associated with higher stress in both groups but no gender interaction was found.
      No association was found between PAS scores and cortisol levels in neither group.
      Children in the ADHD group had a lower ratio of cortisol levels/perceived stress
      on all sampling occasions, built up both by the higher PAS scores and the lower
      cortisol levels in children with ADHD. The higher PAS scores in children with
      ADHD support the validity of the scale. The lack of association between PAS
      scores and diurnal cortisol levels is intriguing and illustrates the complexity
      of the stress concept. Stress-related fragility seems to accompany ADHD during
      childhood.

PMID- 24737122
TI  - Chromatin as dynamic 10-nm fibers.
AB  - Since Flemming described a nuclear substance in the nineteenth century and named
      it "chromatin," this substance has fascinated biologists. What is the structure
      of chromatin? DNA is wrapped around core histones, forming a nucleosome fiber (10
      nm fiber). This fiber has long been assumed to fold into a 30-nm chromatin fiber
      and subsequently into helically folded larger fibers or radial loops. However,
      several recent studies, including our cryo-EM and X-ray scattering analyses,
      demonstrated that chromatin is composed of irregularly folded 10-nm fibers,
      without 30-nm chromatin fibers, in interphase chromatin and mitotic chromosomes.
      This irregular folding implies a chromatin state that is physically less
      constrained, which could be more dynamic compared with classical regular helical
      folding structures. Consistent with this, recently, we uncovered by single
      nucleosome imaging large nucleosome fluctuations in living mammalian cells (~50
      nm/30 ms). Subsequent computational modeling suggested that nucleosome
      fluctuation increases chromatin accessibility, which is advantageous for many
      "target searching" biological processes such as transcriptional regulation.
      Therefore, this review provides a novel view on chromatin structure in which
      chromatin consists of dynamic and disordered 10-nm fibers. 

PMID- 24737124
TI  - Predicting ADHD in school age when using the Strengths and Difficulties
      Questionnaire in preschool age: a longitudinal general population study, CCC2000.
AB  - Indicated prevention of ADHD may reduce impairment and need of treatment in
      youth. The Strengths and Difficulties Questionnaire (SDQ) is a brief
      questionnaire assessing child mental health, reported to be a valid screening
      instrument for concurrent ADHD. This study aimed to examine the validity of using
      the SDQ in preschool age to predict ADHD in school age in a longitudinal design.
      The study population included 2,315 children from the Copenhagen child cohort
      2000 with no prior history of clinically diagnosed ADHD, who were assessed at age
      5-7 years by the SDQ completed by parents and preschool teachers. Danish National
      Registers were used to measure the outcome of any first time ICD-10 diagnosis for
      hyperkinetic disorder or attention-deficit disorder and/or prescription of
      central stimulants during years 2005-2012. Screening potentials of the SDQ's
      predictive algorithms were described, and Cox regression analyses estimated the
      risk of later ADHD diagnosis for screen-positive children. A total of 2.94% of
      the study population were clinically diagnosed and/or were treated with central
      stimulants for ADHD before age 11-12. Children with possible/probable disorder
      according to the SDQ hyperactivity/inattention algorithm showed markedly
      increased risk of a subsequent ADHD diagnosis, hazard ratio 20.65 (CI 95% 12.71
      33.57) and sensitivity 45.6%. Other domains of psychopathology according to the
      SDQ were also associated with an increased risk of receiving a subsequent ADHD
      diagnosis. In summary, we show that the SDQ can identify a group of children with
      highly increased risk of later being diagnosed and/or treated for ADHD in school
      age.

PMID- 24737125
TI  - Recent developments in PET and SPECT imaging.

PMID- 24737128
TI  - Novel methylated biomarkers and a robust assay to detect circulating tumor DNA in
      metastatic breast cancer.
AB  - The ability to consistently detect cell-free tumor-specific DNA in peripheral
      blood of patients with metastatic breast cancer provides the opportunity to
      detect changes in tumor burden and to monitor response to treatment. We developed
      cMethDNA, a quantitative multiplexed methylation-specific PCR assay for a panel
      of ten genes, consisting of novel and known breast cancer hypermethylated markers
      identified by mining our previously reported study of DNA methylation patterns in
      breast tissue (103 cancer, 21 normal on the Illumina HumanMethylation27 Beadchip)
      and then validating the 10-gene panel in The Cancer Genome Atlas project breast
      cancer methylome database. For cMethDNA, a fixed physiologic level (50 copies) of
      artificially constructed, standard nonhuman reference DNA specific for each gene
      is introduced in a constant volume of serum (300 MUL) before purification of the
      DNA, facilitating a sensitive, specific, robust, and quantitative assay of tumor
      DNA, with broad dynamic range. Cancer-specific methylated DNA was detected in
      training (28 normal, 24 cancer) and test (27 normal, 33 cancer) sets of recurrent
      stage IV patient sera with a sensitivity of 91% and a specificity of 96% in the
      test set. In a pilot study, cMethDNA assay faithfully reflected patient response
      to chemotherapy (N = 29). A core methylation signature present in the primary
      breast cancer was retained in serum and metastatic tissues collected at autopsy
      two to 11 years after diagnosis of the disease. Together, our data suggest that
      the cMethDNA assay can detect advanced breast cancer, and monitor tumor burden
      and treatment response in women with metastatic breast cancer.

PMID- 24737130
TI  - Do people understand IARC's 2B categorization of RF fields from cell phones?
AB  - In May 2011, the International Agency on Cancer in Research (IARC) issued an
      official statement concluding that cell phone usage was "possibly carcinogenic to
      humans." There have been considerable doubts that non-experts and experts alike
      fully understood what IARC's categorization actually meant, as "possibly
      carcinogenic" can be interpreted in many ways. The present study is based on an
      online survey indicating that both the characterization of the probability of
      carcinogenicity, as well as the description of the risk increase given in the
      IARC press release, was mostly misunderstood by study participants. Respondents
      also greatly overestimated the magnitude of the potential risk. Our study results
      showed that IARC needs to improve their scientific communications.

PMID- 24737129
TI  - p53 and NF-kappaB coregulate proinflammatory gene responses in human macrophages.
AB  - Macrophages are sentinel immune cells that survey the tissue microenvironment,
      releasing cytokines in response to both exogenous insults and endogenous events
      such as tumorigenesis. Macrophages mediate tumor surveillance and therapy-induced
      tumor regression; however, tumor-associated macrophages (TAM) and their products
      may also promote tumor progression. Whereas NF-kappaB is prominent in macrophage
      initiated inflammatory responses, little is known about the role of p53 in
      macrophage responses to environmental challenge, including chemotherapy or in
      TAMs. Here, we report that NF-kappaB and p53, which generally have opposing
      effects in cancer cells, coregulate induction of proinflammatory genes in primary
      human monocytes and macrophages. Using Nutlin-3 as a tool, we demonstrate that
      p53 and NF-kappaB rapidly and highly induce interleukin (IL)-6 by binding to its
      promoter. Transcriptome analysis revealed global p53/NF-kappaB co-regulation of
      immune response genes, including several chemokines, which effectively induced
      human neutrophil migration. In addition, we show that p53, activated by tumor
      cell paracrine factors, induces high basal levels of macrophage IL-6 in a TAM
      model system [tumor-conditioned macrophages (TCM)]. Compared with normal
      macrophages, TCMs exhibited higher p53 levels, enhanced p53 binding to the IL-6
      promoter, and reduced IL-6 levels upon p53 inhibition. Taken together, we
      describe a mechanism by which human macrophages integrate signals through p53 and
      NF-kappaB to drive proinflammatory cytokine induction. Our results implicate a
      novel role for macrophage p53 in conditioning the tumor microenvironment and
      suggest a potential mechanism by which p53-activating chemotherapeutics, acting
      upon p53-sufficient macrophages and precursor monocytes, may indirectly impact
      tumors lacking functional p53.

PMID- 24737131
TI  - The WHO Health Promoting School framework for improving the health and well-being
      of students and their academic achievement.
AB  - BACKGROUND: The World Health Organization's (WHO's) Health Promoting Schools
      (HPS) framework is an holistic, settings-based approach to promoting health and
      educational attainment in school. The effectiveness of this approach has not been
      previously rigorously reviewed. OBJECTIVES: To assess the effectiveness of the
      Health Promoting Schools (HPS) framework in improving the health and well-being
      of students and their academic achievement. SEARCH METHODS: We searched the
      following electronic databases in January 2011 and again in March and April 2013:
      Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE,
      PsycINFO, CINAHL, Campbell Library, ASSIA, BiblioMap, CAB Abstracts, IBSS, Social
      Science Citation Index, Sociological Abstracts, TRoPHI, Global Health Database,
      SIGLE, Australian Education Index, British Education Index, Education Resources
      Information Centre, Database of Education Research, Dissertation Express, Index
      to Theses in Great Britain and Ireland, ClinicalTrials.gov, Current controlled
      trials, and WHO International Clinical Trials Registry Platform. We also searched
      relevant websites, handsearched reference lists, and used citation tracking to
      identify other relevant articles. SELECTION CRITERIA: We included cluster
      randomised controlled trials where randomisation took place at the level of
      school, district or other geographical area. Participants were children and young
      people aged four to 18 years, attending schools or colleges. In this review, we
      define HPS interventions as comprising the following three elements: input to the
      curriculum; changes to the school's ethos or environment or both; and engagement
      with families or communities, or both. We compared this intervention against
      schools that implemented either no intervention or continued with their usual
      practice, or any programme that included just one or two of the above mentioned
      HPS elements. DATA COLLECTION AND ANALYSIS: At least two review authors
      identified relevant trials, extracted data, and assessed risk of bias in the
      trials. We grouped different types of interventions according to the health topic
      targeted or the approach used, or both. Where data permitted, we performed random
      effects meta-analyses to provide a summary of results across studies. MAIN
      RESULTS: We included 67 eligible cluster trials, randomising 1443 schools or
      districts. This is made up of 1345 schools and 98 districts. The studies tackled
      a range of health issues: physical activity (4), nutrition (12), physical
      activity and nutrition combined (18), bullying (7), tobacco (5), alcohol (2),
      sexual health (2), violence (2), mental health (2), hand-washing (2), multiple
      risk behaviours (7), cycle-helmet use (1), eating disorders (1), sun protection
      (1), and oral health (1). The quality of evidence overall was low to moderate as
      determined by the GRADE approach. 'Risk of bias' assessments identified
      methodological limitations, including heavy reliance on self-reported data and
      high attrition rates for some studies. In addition, there was a lack of long-term
      follow-up data for most studies.We found positive effects for some interventions
      for: body mass index (BMI), physical activity, physical fitness, fruit and
      vegetable intake, tobacco use, and being bullied. Intervention effects were
      generally small but have the potential to produce public health benefits at the
      population level. We found little evidence of effectiveness for standardised body
      mass index (zBMI) and no evidence of effectiveness for fat intake, alcohol use,
      drug use, mental health, violence and bullying others; however, only a small
      number of studies focused on these latter outcomes. It was not possible to meta
      analyse data on other health outcomes due to lack of data. Few studies provided
      details on adverse events or outcomes related to the interventions. In addition,
      few studies included any academic, attendance or school-related outcomes. We
      therefore cannot draw any clear conclusions as to the effectiveness of this
      approach for improving academic achievement. AUTHORS' CONCLUSIONS: The results of
      this review provide evidence for the effectiveness of some interventions based on
      the HPS framework for improving certain health outcomes but not others. More well
      designed research is required to establish the effectiveness of this approach for
      other health topics and academic achievement.

PMID- 24737132
TI  - Combination of MRI and dynamic FET PET for initial glioma grading.
AB  - AIM: MRI and PET with 18F-fluoro-ethyl-tyrosine (FET) have been increasingly used
      to evaluate patients with gliomas. Our purpose was to assess the additive value
      of MR spectroscopy (MRS), diffusion imaging and dynamic FET-PET for glioma
      grading. PATIENTS, METHODS: 38 patients (42 +/- 15 aged, F/M: 0.46) with
      untreated histologically proven brain gliomas were included. All underwent
      conventional MRI, MRS, diffusion sequences, and FET-PET within 3+/-4 weeks.
      Performances of tumour FET time-activity-curve, early-to-middle SUVmax ratio,
      choline / creatine ratio and ADC histogram distribution pattern for gliomas
      grading were assessed, as compared to histology. Combination of these parameters
      and respective odds were also evaluated. RESULTS: Tumour time-activity-curve
      reached the best accuracy (67%) when taken alone to distinguish between low and
      high-grade gliomas, followed by ADC histogram analysis (65%). Combination of time
      activity-curve and ADC histogram analysis improved the sensitivity from 67% to
      86% and the specificity from 63-67% to 100% (p < 0.008). On multivariate logistic
      regression analysis, negative slope of the tumour FET time-activity-curve however
      remains the best predictor of high-grade glioma (odds 7.6, SE 6.8, p = 0.022).
      CONCLUSION: Combination of dynamic FET-PET and diffusion MRI reached good
      performance for gliomas grading. The use of FET-PET/MR may be highly relevant in
      the initial assessment of primary brain tumours.

PMID- 24737133
TI  - Microtubule shuttles on kinesin-coated glass micro-wire tracks.
AB  - Gliding of microtubule filaments on surfaces coated with the motor protein
      kinesin has potential applications for nano-scale devices. The ability to guide
      the gliding direction in three dimensions allows the fabrication of tracks of
      arbitrary geometry in space. Here, we achieve this by using kinesin-coated glass
      wires of micrometer diameter range. Unlike previous methods in which the guiding
      tracks are fixed on flat two-dimensional surfaces, the flexibility of glass wires
      in shape and size facilitates building in-vitro devices that have deformable
      tracks. 

PMID- 24737134
TI  - A review of the anatomy and clinical significance of adrenal veins.
AB  - The adrenal veins may present with a multitude of anatomical variants, which
      surgeons must be aware of when performing adrenalectomies. The adrenal veins
      originate during the formation of the prerenal inferior vena cava (IVC) and are
      remnants of the caudal portion of the subcardinal veins, cranial to the
      subcardinal sinus in the embryo. The many communications between the posterior
      cardinal, supracardinal, and subcardinal veins of the primordial venous system
      provide an explanation for the variable anatomy. Most commonly, one central vein
      drains each adrenal gland. The long left adrenal vein joins the inferior phrenic
      vein and drains into the left renal vein, while the short right adrenal vein
      drains immediately into the IVC. Multiple variations exist bilaterally and may
      pose the risk of surgical complications. Due to the potential for collaterals and
      accessory adrenal vessels, great caution must be taken during an adrenalectomy.
      Adrenal venous sampling, the gold standard in diagnosing primary
      hyperaldosteronism, also requires the clinician to have a thorough knowledge of
      the adrenal vein anatomy to avoid iatrogenic injury. The adrenal vein acts as an
      important conduit in portosystemic shunts, thus the nature of the anatomy and
      hypercoagulable states pose the risk of thrombosis.

PMID- 24737135
TI  - Potential of SNP markers for the characterization of Brazilian cassava germplasm.
AB  - KEY MESSAGE: High-throughput markers, such as SNPs, along with different
      methodologies were used to evaluate the applicability of the Bayesian approach
      and the multivariate analysis in structuring the genetic diversity in cassavas.
      The objective of the present work was to evaluate the diversity and genetic
      structure of the largest cassava germplasm bank in Brazil. Complementary
      methodological approaches such as discriminant analysis of principal components
      (DAPC), Bayesian analysis and molecular analysis of variance (AMOVA) were used to
      understand the structure and diversity of 1,280 accessions genotyped using 402
      single nucleotide polymorphism markers. The genetic diversity (0.327) and the
      average observed heterozygosity (0.322) were high considering the bi-allelic
      markers. In terms of population, the presence of a complex genetic structure was
      observed indicating the formation of 30 clusters by DAPC and 34 clusters by
      Bayesian analysis. Both methodologies presented difficulties and controversies in
      terms of the allocation of some accessions to specific clusters. However, the
      clusters suggested by the DAPC analysis seemed to be more consistent for
      presenting higher probability of allocation of the accessions within the
      clusters. Prior information related to breeding patterns and geographic origins
      of the accessions were not sufficient for providing clear differentiation between
      the clusters according to the AMOVA analysis. In contrast, the F ST was maximized
      when considering the clusters suggested by the Bayesian and DAPC analyses. The
      high frequency of germplasm exchange between producers and the subsequent
      alteration of the name of the same material may be one of the causes of the low
      association between genetic diversity and geographic origin. The results of this
      study may benefit cassava germplasm conservation programs, and contribute to the
      maximization of genetic gains in breeding programs.

PMID- 24737136
TI  - Higher reliability of 18F-FDG target background ratio compared to standardized
      uptake value in vulnerable carotid plaque detection: a pilot study.
AB  - OBJECTIVE: To evaluate the role of [18F]-fluorodeoxyglucose positron emission
      tomography/computer tomography [18F-FDG PET/CT] comparing target background ratio
      (TBR) and standardized uptake value (SUV) with the histopathological inflammatory
      status of the carotid plaques. BACKGROUND: Vulnerable carotid plaques are the
      primary cause of acute cerebrovascular events. 18F-FDG PET/CT represents a morpho
      functional technique able to identify the highly inflamed and most vulnerable
      carotid plaques. Several literature studies experimented this new method to
      identify vascular inflammation, but few have effectively compared PET/CT results
      with plaque histological data and no studies had directly compared TBR to SUV.
      METHODS: Thirty-two consecutive patients (20 men and 12 women, mean age 74 +/- 8
      years) undergoing carotid endarterectomy were enrolled and studied with carotid
      18F-FDG PET/CT. Maximum and mean SUV and TBR were used to quantify 18F-FDG uptake
      while surgical specimens were analyzed by optical microscopy to identify inflamed
      carotid plaques, with evaluation of macrophages infiltration by mean of
      immunohistochemistry. On the basis of the presence of inflammation at the
      histological analysis, we divided population in two groups: group A (n = 12)
      patients with inflamed carotid plaques and group B (n = 20) patients with non
      inflamed ones, then crossed and evaluated the histological data with 18F-FDG
      PET/CT findings. RESULTS: SUV max and SUV mean values resulted higher in group A
      (respectively, 2.14 +/- 0.77 and 1.99 +/- 0.68) than in group B (respectively,
      1.79 +/- 0.37 and 1.64 +/- 0.34) without reaching a statistical significance (p =
      ns). TBR max and TBR mean values resulted higher in group A (respectively, 1.42
      +/- 0.32 and 1.34 +/- 0.26) than in group B (respectively, 1.16 +/- 0.19 and 1.03
      +/- 0.20) with a statistically significant differences between the two groups and
      carotid inflammation (respectively, p < 0.01 and p < 0.001). CONCLUSION: TBR (max
      and mean values) is a more reliable parameter than SUV in identifying inflamed
      plaques. Although limited by the small population analyzed, our results suggest
      the important role of 18F-FDG PET/CT, using TBR, in identification of high-risk
      carotid atherosclerotic plaques.

PMID- 24737137
TI  - Synergy-based small-molecule screen using a human lung epithelial cell line
      yields DeltaF508-CFTR correctors that augment VX-809 maximal efficacy.
AB  - The most prevalent cystic fibrosis transmembrane conductance regulator (CFTR)
      mutation causing cystic fibrosis, DeltaF508, impairs folding of nucleotide
      binding domain (NBD) 1 and stability of the interface between NBD1 and the
      membrane-spanning domains. The interfacial stability defect can be partially
      corrected by the investigational drug VX-809 (3-[6-[[[1-(2,2-difluoro-1,3
      benzodioxol-5-yl)cyclopropyl]carbonyl]amino]-3-methyl-2-pyridinyl]-benzoic acid)
      or the R1070W mutation. Second-generation DeltaF508-CFTR correctors are needed to
      improve on the modest efficacy of existing cystic fibrosis correctors. We
      postulated that a second corrector targeting a distinct folding/interfacial
      defect might act in synergy with VX-809 or the R1070W suppressor mutation. A
      biochemical screen for DeltaF508-CFTR cell surface expression was developed in a
      human lung epithelium-derived cell line (CFBE41o(-)) by expressing chimeric CFTRs
      with a horseradish peroxidase (HRP) in the fourth exofacial loop in either the
      presence or absence of R1070W. Using a luminescence readout of HRP activity,
      screening of approximately 110,000 small molecules produced nine novel corrector
      scaffolds that increased cell surface ?F508-CFTR expression by up to 200% in the
      presence versus absence of maximal VX-809. Further screening of 1006 analogs of
      compounds identified from the primary screen produced 15 correctors with an EC50
      < 5 uM. Eight chemical scaffolds showed synergy with VX-809 in restoring chloride
      permeability in ?F508-expressing A549 cells. An aminothiazole increased chloride
      conductance in human bronchial epithelial cells from a DeltaF508 homozygous
      subject beyond that of maximal VX-809. Mechanistic studies suggested that NBD2 is
      required for the aminothiazole rescue. Our results provide proof of concept for
      synergy screening to identify second-generation correctors, which, when used in
      combination, may overcome the "therapeutic ceiling" of first-generation
      correctors. 

PMID- 24737140
TI  - Redefining the timing of surgery for obstructive sleep apnea in anatomically
      favorable patients.
AB  - OBJECTIVES/HYPOTHESIS: Healthcare remunerating agencies in North America require
      patients with obstructive sleep apnea (OSA) to undergo a continuous positive
      airway pressure (CPAP) trial before funding surgical therapy. The adherence rate
      of CPAP is problematic. This study's objective was to determine the proportion of
      surgically favorable patients who failed CPAP who subsequently benefitted from
      surgical therapy, and to explore consideration of surgical therapy as first-line
      treatment in this specific OSA subpopulation. STUDY DESIGN: This was a
      prospective cohort study. METHODS: Patients with moderate-severe OSA who had
      failed a minimum 6-month trial of CPAP were recruited. All had optimal anatomy
      for surgery and underwent tonsillectomy with palatoplasty +/- septoplasty.
      Outcome measures included apnea-hypopnea index (AHI), Epworth Sleepiness Scale
      (ESS), and Sleep Apnea Quality of Life Index (SAQLI-E), and blood pressure.
      Patients were followed for 1 year. RESULTS: By AHI measurement, 85.7% of patients
      in the entire cohort were successfully treated by surgery. ESS while on CPAP was
      13.7 +/- 2.9, improving to 4.1 +/- 2.5 after surgery. SAQLI-E scores on CPAP were
      25.7 +/- 5.8, improving to 10.2 +/- 3.2 after surgery. Blood pressure remained
      elevated during CPAP but normalized after surgery. All changes were significant
      at P < .001. CONCLUSIONS: Surgical intervention improved OSA severity as measured
      by the ESS, SAQLI-E, and blood pressure. These measures had not improved on CPAP.
      AHI improved as well. Our results suggest that certain patients with OSA may be
      managed more effectively with surgery than CPAP, without confounding issues of
      treatment adherence and with only minor surgical risk. LEVEL OF EVIDENCE: 2
      Laryngoscope 124:S1-S9, 2014.

PMID- 24737138
TI  - Antileukemic activity and mechanism of drug resistance to the marine Salinispora
      tropica proteasome inhibitor salinosporamide A (Marizomib).
AB  - Salinosporamide A (NPI-0052, marizomib) is a naturally occurring proteasome
      inhibitor derived from the marine actinobacterium Salinispora tropica, and
      represents a promising clinical agent in the treatment of hematologic
      malignancies. Recently, these actinobacteria were shown to harbor self-resistance
      properties to salinosporamide A by expressing redundant catalytically active
      mutants of the 20S proteasome beta-subunit, reminiscent of PSMB5 mutations
      identified in cancer cells with acquired resistance to the founding proteasome
      inhibitor bortezomib (BTZ). Here, we assessed the growth inhibitory potential of
      salinosporamide A in human acute lymphocytic leukemia CCRF-CEM cells, and its 10
      fold (CEM/BTZ7) and 123-fold (CEM/BTZ200) bortezomib-resistant sublines harboring
      PSMB5 mutations. Parental cells displayed sensitivity to salinosporamide A (IC50
      = 5.1 nM), whereas their bortezomib-resistant sublines were 9- and 17-fold cross
      resistant to salinosporamide A, respectively. Notably, combination experiments of
      salinosporamide A and bortezomib showed synergistic activity in CEM/BTZ200 cells.
      CEM cells gradually exposed to 20 nM salinosporamide A (CEM/S20) displayed stable
      5-fold acquired resistance to salinosporamide A and were 3-fold cross-resistant
      to bortezomib. Consistent with the acquisition of a PSMB5 point mutation (M45V)
      in CEM/S20 cells, salinosporamide A displayed a markedly impaired capacity to
      inhibit beta5-associated catalytic activity. Last, compared with parental CEM
      cells, CEM/S20 cells exhibited up to 2.5-fold upregulation of constitutive
      proteasome subunits, while retaining unaltered immunoproteasome subunit
      expression. In conclusion, salinosporamide A displayed potent antileukemic
      activity against bortezomib-resistant leukemia cells. beta-Subunit point
      mutations as a common feature of acquired resistance to salinosporamide A and
      bortezomib in hematologic cells and S. tropica suggest an evolutionarily
      conserved mechanism of resistance to proteasome inhibitors. 

PMID- 24737142
TI  - A novel N,P,C cage complex formed by rearrangement of a tricyclic phosphirane
      complex: on the importance of non-covalent interactions.
AB  - The reaction of Li/Cl P-CPh3 phosphinidenoid tungsten(0) complex 2 with
      dimethylcyanamide afforded tricyclic phosphirane complex 4, an unprecedented
      rearrangement of which led to the novel N,P,C cage complex 6. On the basis of DFT
      calculations, formation and intramolecular [3+2] cycloaddition of the transient
      nitrilium phosphane ylide complex 3 to a phenyl ring of the triphenylmethyl
      substituent to give 4 is proposed. Furthermore, theoretical evidence for terminal
      N-amidinophosphinidene complex 7, formed by [2+1] cycloelimination from 4, is
      provided, and the role of the electronic structure and non-covalent interactions
      of intermediate 7 discussed. 

PMID- 24737141
TI  - Retention of fissure sealants in young permanent molars affected by dental
      fluorosis: a 12-month clinical study.
AB  - AIM: To evaluate and compare retention and caries occurance following placement
      of Clinpro and FUJI VII fissure sealants, by two different techniques
      simultaneously in unsealed, contralateral young permanent molars of 7- to 10-year
      old children affected by mild to moderate dental fluorosis at various recall
      intervals of 1 week, 1, 3, 6 and 12 months. STUDY DESIGN: 80 schoolchildren with
      mild to moderate dental fluorosis were assigned to Group A and Group B with 40
      children in each group. In Group A Clinpro fissure sealant and in Group B Fuji
      VII fissure sealant was used. In both the groups fissure sealants were applied by
      conventional fissure sealant technique (CST) on one side and enameloplasty
      sealant technique (EST) on the other side of the same arch. The applied fissure
      sealants were evaluated clinically for retention and caries incidence. RESULTS:
      Clinpro fissure sealant showed a retention rate of 95% when compared with Fuji
      VII (57.5%) at the end of 12 months, which was statistically significant.
      Regarding techniques, EST showed better results than CST in both the groups.
      STATISTICS: Comparison of groups with respect to retention and techniques at
      different time periods was performed using Mann-Whitney U test (p < 0.05).
      Comparison of different time periods with respect to retention and technique in
      all the groups was performed using Wilcoxon matched pairs test by ranks (p <
      0.05). CONCLUSION: Clinpro fissure sealant showed better retention at all
      treatment intervals, when compared with Fuji VII. Further follow-up is required
      to study the efficacy of the fissure sealant placement techniques.

PMID- 24737143
TI  - Effect of aspirin treatment on the prevention of esophageal adenocarcinoma in a
      rat experimental model.
AB  - Aspirin has been proposed in recent years as a candidate for chemoprevention of
      adenocarcinoma in patients with Barrett's esophagus. The aim of the present study
      was to evaluate the effect of acetylsalicylic acid (ASA) in an experimental model
      of esophageal adenocarcinoma. An animal model of gastroenteroesophageal reflux
      was established using Wistar rats undergoing esophagojejunostomy with gastric
      preservation. Following surgery, rats were divided into three groups: i) control
      (vehicle); ii) ASA 50 mg/kg/day; and iii) ASA 5 mg/kg/day. Four months after
      surgery, the surviving animals were sacrificed and the rat esophagi were assessed
      for histological and biochemical [prostaglandin E2 (PGE2) and lipoxin A4 (LXA4 )
      levels] analysis. As in the control rats, those receiving aspirin treatment
      showed no decrease in inflammation grade, extent of ulcerated esophageal mucosa,
      length of intestinal metaplasia in continuity with anastomosis, presence of
      intestinal metaplasia beyond anastomosis, severity of dysplasia or incidence of
      adenocarcinoma. In contrast, aspirin-treated rats showed decreased esophageal
      tissue levels of PGE2 and increased LXA4, significantly in the high-dose aspirin
      group (p=0.008 and p=0.01, respectively). In this rat model of gastroesophageal
      reflux, the administration of aspirin modified esophageal tissue levels of PGE2
      and LXA4, but was not effective in preventing the development of esophageal
      adenocarcinoma. 

PMID- 24737145
TI  - Synthesis and evaluation of a 99mTc-labeled tubulin-binding agent for tumor
      imaging.
AB  - Cholchicine and its derivatives are very potent tubulin-binding compounds and can
      be used as a potential tumor targeting agents. In this study, colchicine was
      labeled with (99m) Tc via hydrazinonicotinic acid (HYNIC) and was investigated
      further. HYNIC/cholchicine was synthesized and labeling with (99m)Tc was
      performed at 95  degrees C for 15 min and radiochemical analysis included HPLC
      method. The stability of radiconjugate was checked in the presence of human serum
      at 37  degrees C up to 24 h. Biodistribution was studied in breast tumor-bearing
      mice. Labeling yield of 95.8 +/- 0.54% was obtained corresponding to a specific
      activity of 54 MBq/umol. Radioconjugate showed good stability in the presence of
      human serum. Biodistribution studies in tumor-bearing mice showed that (99m)
      Tc/HYNIC/colchicine conjugate accumulated in tumor with good uptake (3.17 +/-
      0.14% g/g at 1 h post-injection). The radioconjugate was cleared fast from normal
      organs and showed clearance through urinary and hepatobiliary systems with
      accumulation of activity in kidneys and intestine. This radioconjugate may be
      useful to assess the presence of tumor by imaging.

PMID- 24737144
TI  - Highly heterogeneous, activated, and short-lived regulatory T cells during
      chronic filarial infection.
AB  - The mechanisms underlying the increase in the numbers of regulatory T (Treg)
      cells in chronic infection settings remain unclear. Here we have delineated the
      phenotype and transcriptional profiles of Treg cells from 18 filarial-infected
      (Fil(+) ) and 19 filarial-uninfected (Fil(-) ) subjects. We found that the
      frequencies of Foxp3(+) Treg cells expressing CTLA-4, GITR, LAG-3, and IL-10 were
      significantly higher in Fil(+) subjects compared with that in Fil(-) subjects.
      Foxp3-expressing Treg-cell populations in Fil(+) subjects were also more
      heterogeneous and had higher expression of IL-10, CCL-4, IL-29, CTLA-4, and TGF
      beta than Fil(-) subjects, each of these cytokines having been implicated in
      immune suppression. Moreover, Foxp3-expressing Treg cells from Fil(+) subjects
      had markedly upregulated expression of activation-induced apoptotic genes with
      concomitant downregulation of those involved in cell survival. To determine
      whether the expression of apoptotic genes was due to Treg-cell activation, we
      found that the expression of CTLA-4, CDk8, RAD50, TNFRSF1A, FOXO3, and RHOA were
      significantly upregulated in stimulated cells compared with unstimulated cells.
      Taken together, our results suggest that in patent filarial infection, the
      expanded Treg-cell populations are heterogeneous, short-lived, activated, and
      express higher levels of molecules known to modulate immune responsiveness,
      suggesting that filarial infection is associated with high Treg-cell turnover. 

PMID- 24737146
TI  - Synchronous infection of the aorta and the testis: emphysematous epididymo
      orchitis, abdominal aortic mycotic aneurysm, and testicular artery pseudoaneurysm
      diagnosed by use of MDCT.
AB  - We report clinical details and imaging findings for a case of emphysematous
      epididymo-orchitis with co-existing mycotic abdominal aortic aneurysm and a
      testicular artery pseudoaneurysm in a diabetic 65-year-old male. We report
      imaging findings from ultrasonography (USG) and contrast-enhanced multidetector
      computed tomography (MDCT). Use of MDCT to identify, confirm, and define the
      extent of the disease, and its utility in understanding the pathogenesis of this
      rare condition are highlighted. For such lethal infections, early diagnosis and
      intervention can be lifesaving; imaging can be of crucial importance in this.

PMID- 24737147
TI  - A comparative and retrospective study of three hundred and twenty primary
      Charnley type hip replacements with a minimum follow up of ten years to assess
      whether a dual mobility cup has a decreased dislocation risk.
AB  - PURPOSE: Mid- and long-term follow-up of Charnley total hip arthroplasty (THA)
      demonstrated good functional results with 85 % survivorship at 25-year follow-up.
      However, dislocation still remains an unsolved problem. Dislocation may occur
      throughout the patient's and implant's life. The aim of this study is to answer
      the question: does a dual mobility cup (DMC) decrease the dislocation risk?
      METHODS: We report comparative results at ten years of follow-up of two groups of
      primary cemented Charnley-type THA, one with a standard polyethylene cup (group
      1, n = 215) and the other one with a DMC (group 2, n = 105). RESULTS: In group 1,
      26 dislocations (12.9 %) occurred. In group 2 only one dislocation (0.9 %)
      occurred. This dislocation was successfully reduced by closed reduction, without
      any recurrence. This difference was statistically significant (p = 0.0018). In
      group 1, the reason for revision was recurrent dislocation in 21 cases. Five
      patients were revised for other reasons. The global revision rate was 12.9 %. In
      group 2, two patients needed revision surgery for aseptic loosening. The global
      revision rate was 2.1 %. This difference was statistically significant (p =
      0.054). The goal was reached for the patients of group 2 who had more risks
      factors for dislocation (age, aetiology, American Society of Anesthesiologists
      and Devane scores) than those of group 1. CONCLUSIONS: When using a DMC, we
      observed a low rate of dislocation in primary THA (0.9 %). This surgical choice
      seems to be a safe and effective technique in Charnley-type THA, especially in a
      high-risk population.

PMID- 24737148
TI  - Is the acetabular cup orientation after total hip arthroplasty on a two dimension
      or three dimension model accurate?
AB  - PURPOSE: Malposition of the acetabular component in total hip arthroplasty (THA)
      is a common surgical problem that can lead to hip dislocation, reduced range of
      motion and may result in early loosening. The aim of this study is to validate
      the accuracy and reproducibility of a single x-ray image based 2D/3D
      reconstruction technique in determining cup inclination and anteversion against
      two different computer tomography (CT)-based measurement techniques. METHODS: Cup
      anteversion and inclination of 20 patients after cementless primary THA was
      measured on standard antero-posterior (AP) radiographs with the help of the
      single x-ray 2D/3D reconstruction program and compared with two different 3D CT
      based analyses [Ground Truth (GT) and MeVis (MV) reconstruction model]. RESULTS:
      The measurements from the single x-ray 2D/3D reconstruction technique were
      strongly correlated with both types of CT image-processing protocols for both cup
      inclination [R2=0.69 (GT); R2=0.59 (MV)] and anteversion [R2=0.89 (GT); R2=0.80
      (MV)]. CONCLUSIONS: The single x-ray image based 2D/3D reconstruction technique
      is a feasible method to assess cup position on postoperative x-rays. CT scans
      remain the golden standard for a more complex biomechanical evaluation when a
      lower tolerance limit (+/-2 degrees) is required.

PMID- 24737149
TI  - Is there an association between periprosthetic joint infection and low vitamin D
      levels?
AB  - PURPOSE: Vitamin D is increasingly being recognized as an important mediator of
      immune function and may have a preventive role in the pathogenesis of
      periprosthetic joint infection. To the best of our knowledge, no other study has
      examined possible associations between periprosthetic joint infection and vitamin
      D deficiency. We investigated the rate of vitamin D deficiency in patients
      treated for periprosthetic joint infection and whether vitamin D deficiency is
      independent of other risk factors for vitamin D deficiency in patients with
      periprosthetic joint infection. METHODS: Serum 25-hydroxyvitamin D (25OHD) levels
      of every patient scheduled to receive a total prosthesis either of the hip, knee,
      or shoulder in the orthopaedic department of the Johannes-Guttenberg-University
      Hospital in Mainz, Germany (109 patients), were measured after admission.
      Furthermore, serum 25OHD levels were measured for every patient presenting with
      periprosthetic joint infection (n = 50) or aseptic loosening of the prosthesis (n
      = 31) scheduled to undergo revision surgery. The prevalence of normal (> 30
      ng/ml), insufficient (20-30 ng/ml), and deficient (<20 ng/ml) 25OHD levels was
      determined. RESULTS: All tested patient subgroups showed low vitamin D levels.
      Statistical analysis found no significant difference in vitamin D levels
      comparing patients with prosthesis and patients with aseptic prosthesis loosening
      (p = 0.58). Significant differences in 25OHD levels were found comparing patients
      with periprosthetic joint infection and patients scheduled for primary
      arthroplasty (p < 0.001). In addition, we found a significant difference (p <
      0,001) in 25OHD levels of patients with periprosthetic joint infection compared
      with patients with aseptic prosthesis loosening. CONCLUSION: We found a high
      frequency of vitamin D deficiency in patients being treated by primary
      arthroplasty and those with aseptic joint prosthetic loosening and periprosthetic
      joint infection. Vitamin D deficiency was severe in patients with periprosthetic
      joint infection.

PMID- 24737150
TI  - A new bipolar RRAM selector based on anti-parallel connected diodes for crossbar
      applications.
AB  - Crossbar arrays are the most promising application of a resistive random access
      memory (RRAM) device for achieving high density memory. However, cross-talk
      interference in the crossbar array limits the increase in the integration
      density. In this paper, the combination of two anti-parallel connected diodes and
      a bipolar RRAM cell is proposed to suppress the sneak current in a crossbar array
      with anti-parallel connected diodes as the selector for the bipolar RRAM. By
      using the anti-parallel connected diodes as a selector, the sneak current can be
      effectively suppressed and the high density crossbar array of more than 1 Mb can
      be realized as estimated by the 1/2V read voltage scheme. These results indicate
      that anti-parallel connected diodes can be used as a bipolar selector and have
      great potential for high density bipolar RRAM crossbar array applications. 

PMID- 24737151
TI  - [Milk yield and environmental factors: Multiple regression analysis of the
      association between milk yield and udder health, fertility data and replacement
      rate].
AB  - OBJECTIVE: The relationship between milk yield and both fertility and general
      animal health in dairy herds is discussed from opposing viewpoints. The
      hypothesis (1) that raising the herd milk yield would decrease fertility results,
      the number of milk cells as an indicator for udder health and the replacement
      rate as a global indicator for animal health as well as increasing the occurrence
      of specific diseases as a herd problem was compared to the opposing hypotheses
      that there is no relationship (2) or that there is a differentiated and changing
      relationship (3). MATERIAL AND METHODS: A total of 743 herd examinations,
      considered independent, were performed in 489 herds between 1995 and 2010. The
      milk yield, fertility rate, milk cell count, replacement rate, categorized herd
      problems and management information were recorded. The relationship between the
      milk yield and both the fertility data and animal health was evaluated using
      simple and multiple regression analyses. RESULTS: The period between calving and
      the first service displayed no significant relationship to the herd milk yield.
      Simple regression analysis showed that the period between calving and gestation,
      the calving interval and the insemination number were significantly positively
      associated with the herd milk yield. This positive correlation was lost in
      multiple regression analysis. The milk cell count and replacement rate using both
      the simple and multiple regression analyses displayed a significant negative
      relationship to the milk yield. CONCLUSION AND CLINICAL RELEVANCE: The
      alternative hypothesis (3) was confirmed. A higher milk yield has no negative
      influence on the milk cell count and the replacement rate in terms of the udder
      and general health. When parameterizing the fertility, the herd milk yield should
      be considered. Extending the resting time may increase the milk yield while
      preventing a decline in the insemination index.

PMID- 24737152
TI  - [Influence of feeding rumen-protected choline to transition dairy cows. Part 2:
      Health and reproduction].
AB  - OBJECTIVE: To determine the effects of rumen-protected choline (RPC) on health
      and reproduction in dairy cows. MATERIAL AND METHODS: A total of 298 primi- and
      multiparous German Holstein cows of a high-production dairy herd (average daily
      milk yield: 32 l) were assigned randomly to a control or treatment group and were
      hand fed with 0 or 60 g/d of RPC as ReaShure(r), respectively, from 21 days
      before expected calving to 21 days post partum (p. p.) as a top dressing. Health
      data was analyzed for the incidence of fever within the first 10 days in milk
      (DIM) as well as the incidence of diseases and the culling rate within the first
      200 DIM. Reproduction data were evaluated in terms of the calving data, uterine
      involution on days 10, 21 and 42 p. p., uterine cytology at day 42 p. p.,
      progesterone concentrations during weeks 3 and 5 p. p. and certain fertility
      measures. In the statistical analysis, it was differentiated between the control
      and treatment groups and between primi- and multiparous animals, and their
      interactions were analyzed. RESULTS: The treatment group had less cows with
      subclinical endometritis, higher sickness rates after day 100 p. p., lower
      numbers of stillbirths and more cyclic cows in week 5 p. p. compared to the
      control group (p  <  0.05). Primipara in contrast to multipara had fever more
      frequently, higher rates of subclinical ketosis p. p., metritis and lameness,
      higher numbers of sick cows in the first 30 DIM, higher rates of stillbirths and
      dystocia, showed impaired involution of the uterus on day 10 p. p., fewer animals
      were cyclic during week 5 p. p. and less animals were culled (p < 0.05).
      Statistically significant interactions indicated that more heifers of the
      treatment group were lame, more heifers of the control group developed fever and
      subclinical endometritis, cows of the treatment group suffered more metritis and
      were sick more often in the first 30 DIM, and cows of the control group had more
      dystocia (p < 0.05). CONCLUSION: Overall, supplementing RPC had only minor
      effects on the health status and reproduction. Further research in other dairy
      herds should focus on this topic.

PMID- 24737153
TI  - Behavioural and physiological assessment of stress reactions during vaginal
      examination in dairy cows.
AB  - OBJECTIVES AND AIM: The objective of this study was to determine the origin of an
      arched back in cows during vaginal examination. Moreover, we tested whether the
      duration of an arched back and avoidance reactions during vaginal examination can
      be decreased by epidural anaesthesia or analgesic treatment. MATERIAL AND
      METHODS: Behaviour during cleaning of the perivaginal region and during vaginal
      examination was scored using the avoidance reactivity score (ARS). Heart rate
      (HR) was recorded in 10 dairy cows considering four experimental phases, i.e.
      baseline, cleaning the perivaginal region, vaginal examination and post
      examination. Each cow was examined three times and received no treatment (CON),
      an epidural anaesthesia (EPID) or an analgesic treatment (NSAID). The duration of
      an arched back during and post-examination was measured. RESULTS: The expression
      of the arched back was shortest in cows of group EPID and longest in cows of
      group CON. Avoidance reactions did not differ between the cleaning phase and
      vaginal examination in cows of group EPID. Cows of group CON showed the strongest
      avoidance reactions during examination, whereas cows of group EPID showed least
      avoidance reactions. Mean HR increased during cleaning and vaginal examination
      and decreased post-examination. Mean HR during vaginal examination did not differ
      between treatment groups. CONCLUSION: The results show that cows express
      discomfort during vaginal examination with an increase in avoidance reactions and
      HR. Although epidural anaesthesia could reduce sensitivity in the perivaginal
      region, cows still felt the urge to empty the vagina from the examiner's hand
      and, thus, were arching their back. CLINICAL RELEVANCE: In practice, routine
      vaginal examinations in dairy cows have not been considered as invasive examina-
      tions. Our results show that vaginal examinations indeed do cause discomfort. We
      do not suggest the application of any anaesthetic treatment as appropriate before
      routine vaginal examinations. Nonetheless, the examiner should be aware of the
      stress potential of vaginal examinations and conduct such examinations most
      carefully.

PMID- 24737154
TI  - Antibody reaction in immunologically naive replacement gilts vaccinated with an
      attenuated PRRSV live vaccine.
AB  - OBJECTIVE: Serological testing of blood samples is commonly known as an approved
      method to diagnose infectious diseases. Likewise it is used for monitoring
      infectious diseases as it is fast and cost-effective. Nevertheless interpretation
      of results can be difficult, especially when the samples were taken from animals,
      which received a vaccination prior to the serological examination. This is mainly
      due to the fact, that not every vaccination induces a measurable antibody
      reaction. In this recent case gilts were vaccinated with an attenuated live
      vaccine and the serum samples were negative in the ELISA. The question aroused
      which serological reaction to a vaccine is expected under field conditions.
      MATERIAL AND METHODS: In order to clarify this question a group of 28 gilts
      negative for porcine reproductive and respiratory syndrome (PRRS) virus (from a
      verifiable PRRSV-negative stock) were vaccinated with an attenuated PRRSV vaccine
      and blood samples were taken on days 0, 2, 4, 8 and 15 post vaccinationem (p.
      vacc). To provide a reliable means of diagnosis the samples were tested with an
      antibody ELISA and RT-PCR. RESULTS: A replication of the vaccine virus was
      demonstrated via RT-PCR in 100% of the animals 4 days p. vacc. The first samples
      classified positive in the ELISA were detected 8 days p. vacc. On day 15 p. vacc.
      a positive serological result was obtained for all animals. CONCLUSION: The
      vaccination with an attenuated PRRSV vaccine provides a pronounced antibody
      reaction under field conditions. In case of a negative serological reaction in
      recently vaccinated pigs all steps from the manufacturing process through to the
      implementation of the vaccine have to be critically evaluated. Likewise correct
      laboratory studies and the assessment of diagnostic results need to be
      scrutinized.

PMID- 24737155
TI  - [Congenital embryonal rhabdomyosarcoma of the head in a red and white German
      Holstein calf].
AB  - Tumours with skeletal-muscle differentiation are rare in companion animals. They
      are differentiated into benign rhabdomyomas and malignant rhabdomyosarcomas. A
      female German Holstein calf displayed a congenital, spherical, subcutaneous mass
      at the lateral side of the head. Histology revealed an encapsulated, expansile,
      highly cellular mass consisting of a reticular meshwork of moderately
      pleomorphic, small spindle-shaped to round cells within a fibrovascular to myxoid
      stroma as well as multifocal, large, blunt, multinucleated myotube-like cells
      (strap cells). Electron microscopy demonstrated characteristic cytoplasmic
      bundles of myofilaments and Z-stripes within the strap cells. Immunoreactivity
      for vimentin was observed in the small spindle-shaped cells and for desmin in the
      strap cells. The results are consistent with the spectrum of findings
      characteristic for a bovine congenital embryonal rhabdomyosarcoma. 

PMID- 24737156
TI  - [Torsion of a liver cyst in a calf].
AB  - A 7-day-old male calf was presented because of an abdominal distension and a
      reduced feed intake. Sonographic examination showed a multi-chambered mass with
      anechoic content, separated by numerous hyperechoic septa in the ventral aspect
      of the abdomen. During diagnostic laparotomy, the cystic mass adhering to the
      diaphragmatic surface of the liver was determined to be a liver cyst with a 720
      degrees -torsion separating the cyst into two parts. A complete resection of the
      pedunculated cyst was achieved. The calf recovered completely and body-weight
      gain following surgery was typical for its age and breed. Histopathological
      examination of the cystic wall confirmed the diagnosis of a serosal liver cyst. 

PMID- 24737157
TI  - [Clinical relevant procedures for early pregnancy diagnosis in the mare].
AB  - This review describes stepwise the recto-manual and transrectal ultrasonographic
      evidence of early pregnancy detection in the horse. The morphological and
      physiological conditions in the individual phases of early pregnancy are
      presented in correlation to the potential clinical findings. The importance of
      embryonic and early foetal losses is presented. Communication and documentation
      of findings are also addressed. The final section is devoted to the evaluation of
      the examination effort. In this regard, it is emphasized that the gynaecological
      examination for the evaluation of the pregnancy status represents a service
      contract. 

PMID- 24737158
TI  - Asymmetric addition of triethylaluminium to aromatic aldehydes catalyzed by
      titanium-(5,5'-biquinoline-6,6'-diol) complexes.
AB  - A novel convenient procedure for the resolution of 5,5'-biquinoline-6,6'-diol
      (BIQOL) was achieved by separating the corresponding diastereomeric mixture of
      (S)-(+)-camphorsulfonates on a semiprepared XDB-C8 column followed by hydrolysis.
      The efficient asymmetric addition of triethylaluminium to aromatic aldehydes
      catalyzed by Ti-(+)/(-)BIQOL complexes under mild conditions is described. The
      reactions led to the formation of 1-arylpropan-1-ol in up to 87.5% ee.

PMID- 24737160
TI  - Experimental validations of in vivo human musculoskeletal tissue conductivity
      images using MR-based electrical impedance tomography.
AB  - Magnetic resonance (MR)-based electrical impedance tomography (MREIT) is a widely
      used imaging technique that provides high-resolution conductivity images at DC or
      below the 1 kHz frequency range. Using an MR scanner, this technique injects
      imaging currents into the human body and measures induced internal magnetic flux
      density data. By applying the recent progress of MREIT techniques, such as
      chemical shift artifact correction, multi-echo pulse sequence, and improved
      reconstruction algorithm, we can successfully reconstruct conductivity images of
      the human body. Meanwhile, numerous studies reported that the electrical
      conductivity of human tissues could be inferred from in vitro or ex vivo
      measurements of different species. However, in vivo tissues may differ from in
      vitro and/or ex vivo state due to the complicated tissue responses in living
      organs. In this study, we performed in vivo MREIT imaging of a human lower
      extremity and compared the resulting conductivity images with ex vivo biological
      tissue phantom images. The human conductivity images showed unique contrast
      between two different types of bones, muscles, subcutaneous adipose tissues, and
      conductive body fluids. Except for muscles and adipose tissues, the human
      conductivity images showed a similar pattern when compared with phantom results
      due to the anisotropic characteristic of muscle and the high conductive fluids in
      the adipose tissue.

PMID- 24737161
TI  - Involvement of Rac in thromboxane A2-induced human platelet activation:
      regulation of sCD40 ligand release and PDGF-AB secretion.
AB  - We have previously shown that glycoprotein Ib/IX/V activation stimulates the
      release of the soluble CD40 ligand (sCD40L) via the generation of thromboxane A2
      from human platelets. In the present study, the role of Rac, which is a member of
      the Rho family, was investigated in the thromboxane A2-stimulated release of
      platelet-derived growth factor (PDGF)-AB and sCD40L in human platelets. U46619, a
      thromboxane receptor agonist, stimulated the activation of Rac time-dependently
      in human platelets, and NSC23766, a selective inhibitor of the Rac-guanine
      nucleotide exchange factor interaction, reduced the U46619-induced platelet
      aggregation. NSC23766 markedly suppressed the U46619-induced p38 mitogen
      activated protein (MAP) kinase phosphorylation. The thromboxane A2-induced
      release of PDGF-AB and sCD40L was significantly suppressed by NSC23766 in a dose
      dependent manner. In addition, NSC23766 reduced the sCD40L release stimulated by
      ristocetin, a glycoprotein Ib/IX/V activator. These results indicate that Rac
      regulates the thromboxane A2-induced stimulation of PDGF-AB secretion and sCD40L
      release via the p38 MAP kinase in human platelets. 

PMID- 24737162
TI  - Secondary hemophagocytic lymphohistiocytosis (HLH) from a presumed brown recluse
      spider bite.
AB  - Systemic loxoscelism is a rare complication after Loxosceles reclusa (brown
      recluse spider) envenomation. Loxosceles venom contains pro-inflammatory
      proteins, which have been shown to be elevated in patients with hemophagocytic
      lymph histiocytosis. We present a case of a 10-year-old male that developed
      presumed systemic loxoscelism, secondary hemophagocytic lymphohistiocytosis with
      hepatic dysfunction and renal failure. He was treated with dexamethasone and made
      a full recovery. 

PMID- 24737163
TI  - Low TCR signal strength induces combined expansion of Th2 and regulatory T cell
      populations that protect mice from the development of type 1 diabetes.
AB  - AIMS/HYPOTHESIS: Weak stimulation of CD4(+) T cells induces expansion of CD4(+)
      forkhead box P3(+) regulatory T cells (Tregs) and can also promote T helper (Th)
      2 responses, which have demonstrable beneficial effects on autoimmune diabetes.
      This study explored the feasibility of combined Treg/Th2 expansion for
      immunotherapy of type 1 diabetes in NOD mice. METHODS: We compared Treg and Th
      responses to dendritic cells (DC) presenting scaled antigen doses to islet
      specific NOD CD4(+) T cells. Flow cytometric and Luminex analyses were performed
      to determine the phenotype and cytokine profile of expanded T cells. The ability
      of expanded T cells to prevent type 1 diabetes was tested in an adoptive transfer
      model. RESULTS: In vitro studies revealed a hierarchical, selective expansion of
      Treg and T effector (Teff) populations at different antigen doses. Thus, a single
      low dose produced a mixture of Tregs Th2 and type 1 regulatory (Tr1) cells, which
      prevented diabetes in NOD-SCID mice and increased the ratio of Treg/Teff cells
      infiltrating the pancreatic islets. Subcutaneous injection of DC, previously
      shown to prevent diabetes in NOD mice, induced expansion of the same mixture of
      Tregs Tr1 and Th2 cells. Low-dose expansion of Treg required MHC-T cell receptor
      interaction and was partly dependent on T cell derived TGF-beta and IL-2.
      Autocrine IFN-gamma was required for the promotion of diabetogenic Th1 cells at
      high antigen doses. CONCLUSIONS/INTERPRETATION: Weak stimulation of CD4(+) T
      cells with DC and low-dose antigen expands a combination of antigen-specific
      Tregs Th2 and Tr1 cells that prevent autoimmunity, without the need to target or
      purify specific Treg populations.

PMID- 24737164
TI  - Surface modification of layered zirconium phosphates: a novel pathway to
      multifunctional materials.
AB  - The intercalation of inorganic layered materials has resulted in a wide range of
      applicability. In such cases the applicability of the material is largely
      dependent upon the species intercalated within the layer, and the layered
      material acts largely as a host. Recently, the surface modification of inorganic
      layered materials has been investigated and it has been shown that the exterior
      layers can be exclusively functionalized. The advent of surface chemistry allows
      for the synthesis of particles with both a controlled interlayer and surface.
      This approach can be used to tailor nanoparticles for specific applications.
      Herein we review the surface chemistry of alpha-zirconium bis(monohydrogen
      orthophosphate) monohydrate (Zr(HPO4)2.H2O, alpha-ZrP) along with some
      applications of recent interest. Not only can these reactions be applied to alpha
      ZrP, but similar chemistry can also be expanded to other layered materials and
      systems. 

PMID- 24737166
TI  - Prognostic relevance of glycosylation-associated genes in breast cancer.
AB  - Glycosylation of cellular proteins has important impact on their stability and
      functional properties, and glycan structures strongly influence cell adhesion.
      Many enzymes are involved in glycoconjugate synthesis and degradation, but there
      is only limited information about their role in breast cancer progression.
      Therefore, we retrieved RNA expression data of 202 glycosylation genes generated
      by microarray analysis (Affymetrix HG-U133A) in a cohort of 194 mammary
      carcinomas with long-term follow-up information. After univariate and
      multivariate Cox regression analysis, genes with independent prognostic value
      were identified. These were further analysed by Kaplan-Meier analysis and log
      rank tests, and their prognostic value was validated in a second cohort of 200
      tumour samples from patients without systemic therapy. In our first cohort, we
      identified 24 genes with independent prognostic value, coding for sixteen
      anabolic and eight catabolic enzymes. Functionally, these genes are involved in
      all important glycosylation pathways, namely O-glycosylation, N-glycosylation, O
      fucosylation, synthesis of glycosaminoglycans and glycolipids. Eighteen genes
      also showed prognostic significance in chemotherapy-treated patients. In the
      second cohort, six of the 24 relevant genes were of prognostic significance
      (FUT1, FUCA1, POFUT1, MAN1A1, RPN1 and DPM1), whereas a trend was observed for
      three additional probesets (GCNT4, ST3GAL6 and UGCG). In a stratified analysis of
      molecular subtypes combining both cohorts, great differences appeared suggesting
      a predominant role of N-glycosylation in luminal cancers and O-glycosylation in
      triple-negative ones. Correlations of gene expression with metastases of various
      localizations point to a role of glycan structures in organ-specific metastatic
      spread. Our results indicate that various glycosylation reactions influence
      progression and metastasis of breast cancer and might thus represent potential
      therapeutic targets. 

PMID- 24737165
TI  - Aberrant expression of claudin-4 and -7 in hepatocytes in the cirrhotic human
      liver.
AB  - The liver comprises hepatocytes and non-parenchymal cells such as bile duct
      epithelial cells. Claudin-4 and -7 are not expressed in hepatocytes under
      physiological conditions. It was reported that claudin-7 increased in human
      pulmonary fibroses. We therefore investigated claudin-4 and -7 expressions in
      human cirrhotic livers, in which hepatocyte proliferation is severely delayed. We
      examined liver tissues from 50 patients with liver tumors. The expression of
      claudin-4 and -7 in hepatocytes significantly increased with the grade of
      fibrosis, not with inflammatory activity, in the liver tissues of chronic
      hepatitis. The number of claudin-4- and -7-positive cells observed was greater
      than that of alpha-fetoprotein-positive hepatic progenitor cells. In primary
      cultures of mouse hepatocytes, the expression of claudin-4 and -7 was not induced
      by treatment with proinflammatory cytokines. In immunohistochemical analysis of
      liver tissues of 3,5-diethoxycarbonyl-1,4-dihydrocollidine-treated mice and
      primary cultures of mouse hepatocytes, the expression of claudin-4 and -7
      increased with proliferation of progenitor cells. However, the claudin-4- and -7
      positive cells were not always progenitor cells. Thus, claudin-4 and -7 were
      observed in hepatocytes of severely damaged mouse and human livers. These
      findings suggest that claudin-4- and -7-positive hepatocytes may exist during the
      process of differentiation from progenitor cells into mature hepatocytes. 

PMID- 24737167
TI  - Adolescent dietary fiber, vegetable fat, vegetable protein, and nut intakes and
      breast cancer risk.
AB  - The importance of early-life exposures in breast cancer development is
      increasingly recognized. However, limited research has evaluated the relationship
      between adolescent diet and subsequent risk of breast cancer and reported
      inconsistent results. This population-based case-control study investigated the
      associations of dietary fiber, vegetable protein, vegetable fat, and nuts
      consumed during adolescence with adult breast cancer risk. Women, ages 25-74
      years, who were diagnosed with first primary breast cancer between 2002 and 2003,
      were identified using the Ontario Cancer Registry. Controls were identified
      through random-digit dialing and age-frequency matched to cases. Diet at ages 10
      15 was assessed with a 55-item food frequency questionnaire among 2,865 cases and
      3,299 controls. Logistic regression was performed to estimate odds ratios (ORs)
      and 95 % confidence intervals (CIs). Inverse associations were found between
      intakes of dietary fiber, vegetable protein, vegetable fat, and nuts during
      adolescence and breast cancer risk, which persisted after controlling for adult
      intakes. The ORs (95 % CI) for the highest versus the lowest quintile of intake
      were 0.66 (0.55-0.78; P trend < 0.0001) for fiber, 0.80 (0.68-0.95; P trend =
      0.01) for vegetable protein, 0.74 (0.63-0.87; P trend = 0.002) for vegetable fat,
      and 0.76 (0.61-0.95 for >=1 serving/day vs. <1 serving/month intake; P trend =
      0.04) for nuts. The reduced risk for adolescent intakes of fiber, vegetable
      protein, and nuts was largely limited to postmenopausal women (P interaction <=
      0.05). Dietary fiber, vegetable protein, vegetable fat, and nuts consumed during
      adolescence were associated with reduced breast cancer risk. 

PMID- 24737168
TI  - RANK expression as a prognostic and predictive marker in breast cancer.
AB  - RANK ligand (RANKL) is crucial for the development of mouse mammary glands during
      pregnancy. RANKL functions as a major paracrine effector of the mitogenic action
      of progesterone in mammary epithelium via its receptor RANK and has a role in
      expansion and regenerative potential of mammary stem cells. Pharmacologic
      inhibition of RANKL attenuates the development of mammary carcinoma and inhibits
      metastatic progression in multiple mouse models. Primary breast carcinoma samples
      from the neoadjuvant GeparTrio study were analyzed to correlate the expression of
      human RANK and RANKL with pathological complete response (pCR), disease-free
      (DFS), and overall (OS) survival. Pre-treatment FFPE core biopsies (n = 601) were
      analyzed for percentage and intensity of immunohistochemical RANK and RANKL
      expression. Antibodies against human RANK (N-1H8; Amgen) and human RANKL (M366;
      Amgen) were used. RANK protein was expressed in 160 (27 %) patients. Increased
      RANK expression was observed in 14.5 % of patients and correlated with high tumor
      grade (p < 0.023) and negative hormone receptor (HR) status (p < 0.001). Patients
      with high RANK expression showed a higher pCR rate (23.0 % vs. 12.6 %, p =
      0.010), shorter DFS (p = 0.038), and OS (p = 0.011). However, prognostic and
      predictive information was not an independent parameter. Only 6 % of samples
      expressed RANKL, which was not correlated with any clinical features. Higher RANK
      expression in the primary tumor is associated with a higher sensitivity to
      chemotherapy, but also a higher risk of relapse and death. Our study provides a
      basis for further exploration of the antitumor activity of clinical antibodies
      against RANKL. 

PMID- 24737169
TI  - A rare case of conjugal amyotrophic lateral sclerosis.

PMID- 24737170
TI  - Increased alpha-synuclein levels in the cerebrospinal fluid of patients with
      Creutzfeldt-Jakob disease.
AB  - Recent studies have shown that cerebrospinal fluid (CSF) levels of alpha
      synuclein (alpha-syn) are highly elevated in patients with Creutzfeldt-Jakob
      disease (CJD) compared to controls. However, the diagnostic value of CSF alpha
      syn in CJD has not been established. To confirm whether CSF alpha-syn is
      increased in CJD and is a useful marker for this disease, two independent enzyme
      linked immunoabsorbent assays (ELISAs) specific for alpha-syn were used: ELISA
      211-FL140, which is specific for full-length alpha-syn, and ELISA N19-FL140,
      which is specific for the full-length and associated C-terminal truncated forms
      of alpha-syn. CSF samples from 24 patients with CJD and 24 controls were assessed
      in this study. We found that samples from the CJD patients showed significantly
      higher levels of CSF alpha-syn compared to controls in both ELISA (211-FL140 or
      N19-FL140) tests (P = 0.0467 and P = 0.0010, respectively). However, there was a
      considerable overlap in the concentration ranges of the two groups of subjects.
      We also measured the levels of total tau (t-tau) protein in these samples and
      found that CSF t-tau levels were 5-10-times higher in the CJD group (P < 0.0001)
      compared with the controls. When the CSF t-tau and alpha-syn levels were
      combined, the area under the ROC curve (AUC) was slightly increased in clinically
      diagnosed CJD cases (AUC of 0.964) relative to an AUC of 0.943 for increased CSF
      t-tau alone. The combined use of CSF alpha-syn and t-tau levels may be a useful
      biomarker for the diagnosis of CJD.

PMID- 24737172
TI  - A glutathione-activated phthalocyanine-based photosensitizer for photodynamic
      therapy.
AB  - A zinc(II) phthalocyanine substituted with a 2,4-dinitrobenzenesulfonate group
      has been prepared. Its fluorescence emission and reactive oxygen species
      generation can be greatly enhanced by glutathione in phosphate-buffered saline
      and inside MCF-7 cells. This compound thus functions as a highly efficient
      molecular-based activatable photosensitizer. 

PMID- 24737171
TI  - Detecting nocturnal hypertension in Parkinson's disease and multiple system
      atrophy: proposal of a decision-support algorithm.
AB  - A pathological nocturnal blood pressure (BP) profile, either non-dipping or
      reverse dipping, occurs in more than 50% of subjects diagnosed with multiple
      system atrophy (MSA) or Parkinson's disease (PD). This may play a negative
      prognostic role in alpha-synucleinopathies, but, being mostly asymptomatic,
      remains largely underdiagnosed. In this proof-of-concept study, we aimed at
      developing a decision-support algorithm to predict pathological nocturnal BP
      profiles during a standard tilt-table examination in PD and MSA. Sixteen MSA and
      16 PD patients underwent standard tilt-table examination and 24-h ambulatory BP
      monitoring (24-h ABPM). Clinical and tilt test differences between patients with
      a normal and a pathological nocturnal BP profile at 24-h ABPM were assessed, and
      a decision-support algorithm was developed accordingly. 75% of MSA and 31 % of PD
      patients showed a pathological nocturnal BP profile. This was associated with
      more pronounced orthostatic BP drop (p = 0.03), joint occurrence of orthostatic
      hypotension and supine hypertension (p = 0.046), and lack of BP overshoot in the
      late phase II (II_L, p = 0.002) and in the phase IV (p = 0.007) of the Valsalva
      manoeuvre. Combined ?BP <=0.5 mmHg in the II_L and <=-7 mmHg in the IV phase of
      Valsalva manoeuvre correctly predicted a pathological nocturnal BP profile with
      87.5% sensitivity and 85.7% specificity. Pathological nocturnal BP profiles are
      associated with evidence of cardiovascular noradrenergic failure in PD and MSA.
      The Valsalva manoeuvre is routinely performed during standard tilt-table
      examinations. We propose the naked-eye evaluation of Valsalva phase II_L and
      phase IV BP behaviour as time-sparing screening tool for pathological nocturnal
      BP profiles in PD and MSA.

PMID- 24737173
TI  - Role of tumor-associated macrophages in the angiogenesis of well-differentiated
      hepatocellular carcinoma: pathological-radiological correlation.
AB  - The role of tumor-associated macrophages (TAMs) in hepatocellular carcinoma (HCC)
      has not been fully investigated. The aim of the present study was to clarify
      whether TAMs are associated with the angiogenesis of HCC during its multistep
      development, especially at an early stage. Forty-three well-differentiated HCCs
      and 30 well- to moderately differentiated HCCs (nodule-in-nodule lesion) were
      used. We immunohistochemically assessed microvessel density (by CD34) and
      macrophage count (by CD68 or CD163). Computed tomography hepatic angiography
      (CTHA) was performed for 26 well-differentiated HCCs and all 30 well- to
      moderately differentiated HCCs. The pathological analysis of the 43 well
      differentiated HCCs revealed a positive correlation between microvessel density
      and macrophage count (p=0.0026, r=0.4486). Based on the CTHA findings, 26 well
      differentiated HCCs classified into a hyperattenuation group (n=14) and a hypo-
      or isoattenuation group (n=12). The microvessel density and macrophage count of
      the hyperattenuation group were significantly higher than those of the hypo- or
      isoattenuation group (p=0.0372 and p=0.0476). In the 30 well- to moderately
      differentiated HCCs, microvessel density of the moderately differentiated
      components was significantly higher than that of the well-differentiated
      components (p<0.0001). However, the macrophage count of the moderately
      differentiated component was significantly lower than that of the well
      differentiated component (p<0.0001). All the moderately differentiated components
      showed marked hyperattenuation on CTHA. Tumor vascularity was correlated with
      macrophage count in the tumor when limited to well-differentiated HCCs. TAMs may
      have a role in promoting angiogenesis of HCC at an early stage during its
      multistep development. 

PMID- 24737174
TI  - Management of pseudoaneurysms of the internal carotid artery in postirradiated
      nasopharyngeal carcinoma patients.
AB  - OBJECTIVES/HYPOTHESIS: Massive epistaxis due to ruptured pseudoaneurysm of the
      internal carotid artery (ICA) is an often fatal complication of radiation
      treatment for patients with nasopharyngeal carcinoma. We review the clinical
      characteristics and predictors of survival in patients suffering from this
      serious complication after radiotherapy. STUDY DESIGN: Retrospective case series.
      METHODS: Clinical records and radiological investigations of postirradiated NPC
      patients with ICA pseudoaneurysm diagnosed with digital subtraction angiography
      in Queen Mary Hospital from January 2003 to December 2012 were reviewed. Risk
      factors analyzed for survival included gender, size of initial tumor, history of
      second course of radiotherapy, history of previous maxillary swing
      nasopharyngectomy, presence of persistent disease, successful initial hemostasis,
      successful airway control, and endovascular treatment. RESULTS: Twenty-six were
      included in the analysis. Twenty-three patients underwent endovascular treatment,
      and 20 (87%) had successful control of the bleeding. Eighteen (69%) patients
      survived. Univariate analysis showed that successful temporary control of
      bleeding and airway control were associated with survival. CONCLUSIONS: Prompt
      bleeding control and airway management is necessary to improve survival.
      Endovascular treatment is a good definitive treatment option with a high success
      rate.

PMID- 24737175
TI  - Psychological effects and outcome predictors of three bariatric surgery
      interventions: a 1-year follow-up study.
AB  - PURPOSE: Weight loss surgery efficacy has been demonstrated for morbid obesity.
      Different outcomes have been hypothesized, according to specific bariatric
      surgery interventions and psychological characteristics of obese patients. The
      present study compared three different surgery procedures, namely laparoscopic
      adjustable gastric band (LAGB), Roux-en-Y gastric bypass (RYGB) and
      biliopancreatic diversion (BPD), in terms of weight loss efficacy and
      psychological outcomes. METHODS: Eighty-three subjects seeking bariatric surgery
      have been evaluated before and 12 months after surgery intervention, by means of
      a clinical interview and different self-reported questionnaires, including Eating
      Disorder Examination Questionnaire, Emotional Eating Scale, Binge Eating Scale,
      Beck Depression Inventory, Symptom Checklist and State-Trait Anxiety Inventory.
      RESULTS: BPD group (26 subjects) showed the greatest weight loss, followed by
      RYGB (30 subjects), and LAGB group (27 subjects). All the treatments were
      associated with a significant improvement of anxiety, depression, and general
      psychopathology, and a similar pattern of reduction of binge eating
      symptomatology. BPD group reported a greater reduction of eating disorder
      psychopathology, compared to the other groups. Pre-treatment emotional eating
      severity was found to be a significant outcome modifier for the three treatment
      interventions. CONCLUSIONS: These results suggest that all the three types of
      bariatric surgery significantly improved psychopathology and eating disordered
      behaviors. They also support the importance of a pre-treatment careful
      psychological assessment in order to supervise the post-surgical outcome.

PMID- 24737176
TI  - Autoimmune priming, tissue attack and chronic inflammation - the three stages of
      rheumatoid arthritis.
AB  - Extensive genome-wide association studies have recently shed some light on the
      causes of chronic autoimmune diseases and have confirmed a central role of the
      adaptive immune system. Moreover, better diagnostics using disease-associated
      autoantibodies have been developed, and treatment has improved through the
      development of biologicals with precise molecular targets. Here, we use
      rheumatoid arthritis (RA) as a prototype for chronic autoimmune disease to
      propose that the pathogenesis of autoimmune diseases could be divided into three
      discrete stages. First, yet unknown environmental challenges seem to activate
      innate immunity thereby providing an adjuvant signal for the induction of
      adaptive immune responses that lead to the production of autoantibodies and
      determine the subsequent disease development. Second, a joint-specific
      inflammatory reaction occurs. This inflammatory reaction might be clinically
      diagnosed as the earliest signs of the disease. Third, inflammation is converted
      to a chronic process leading to tissue destruction and remodeling. In this
      review, we discuss the stages involved in RA pathogenesis and the experimental
      approaches, mainly involving animal models that can be used to investigate each
      disease stage. Although we focus on RA, it is possible that a similar stepwise
      development of disease also occurs in other chronic autoimmune settings such as
      multiple sclerosis (MS), type 1 diabetes, and systemic lupus erythematosus. 

PMID- 24737177
TI  - Multiconfigurational character of the ground states of polycyclic aromatic
      hydrocarbons. A systematic study.
AB  - A systematic study of the electronic structure of polycyclic hydrocarbons from
      naphthalene to a system containing 80 fused benzene has been carried out.
      Geometries were optimized for closed shell singlet, open shell singlet, triplet
      and multiplet states at B3LYP/cc-pVDZ level of theory, D1 (second order Moller
      Plesset) and D1 (second-order approximate coupled-cluster) diagnostics have been
      calculated for studied molecules. Complete active space self-consistent field
      (10,10)/6-31G(d) single point energy calculations have been carried out for all
      optimized structures. Multireference character of the ground state becomes
      important when the number of atoms in the polycyclic hydrocarbon exceeds 40-50.
      At this point, D1 diagnostics reaches 0.04-0.05 and the squared configuration
      interaction expansion coefficient for dominant configuration drops to about 0.6.
      However, only for the three largest systems predominantly polyradicalic ground
      states have been detected. All other polycyclic hydrocarbons showing significant
      multiconfigurational character of singlet ground state have only two dominant
      configurations which are closed shell singlet and doubly excited singlet,
      respectively. Thus, small polycyclic hydrocarbons have mostly single reference
      singlet ground state, the medium size systems have notably multireference ground
      state (singlet or triplet) with only moderate polyradicalic character. The ground
      state of largest systems is singlet polyradical. 

PMID- 24737178
TI  - Large enhancements of NaYF4:Yb/Er/Gd nanorod upconversion emissions via coupling
      with localized surface plasmon of Au film.
AB  - Four-layered plasmonic structures of glass/Au/TiO2/NaYF4:Yb, Er, Gd nanorods were
      fabricated and tremendous improvement in upconversion luminescence (UCL) was
      observed under infrared 980 nm excitation. The TiO2 film was used as an oxide
      spacer. The emission intensity of the upconversion (UC) nanorods was strongly
      modulated by the thickness of the TiO2 layer. The extent of modulation depended
      on the separation distance between the Au layer and UC nanorods. A maximum UCL
      enhancement of 192-fold was observed for one green emission (540 nm) when a 10 nm
      thick TiO2 film was used; 150-fold was observed for the other green emission (521
      nm) at the same thickness of TiO2; and 105-fold was observed for the red emission
      (654 nm) when a 7.5 nm-thick TiO2 film was used. Alteration of the radiative
      decay rate was demonstrated for the first time in measurements of the decay times
      of UC nanorods positioned at various distances from the Au layer. The light
      interaction and coupling between metal Au and UC nanorods is numerically studied.
      The UCL mechanisms of multilayer plasmonic structures are discussed. Experimental
      results are explained and correspond well with those of theoretical calculations.

PMID- 24737180
TI  - Purely electronic switching with high uniformity, resistance tunability, and good
      retention in Pt-dispersed SiO2 thin films for ReRAM.
AB  - Resistance switching memory operating by a purely electronic switching mechanism,
      which was first realized in Pt-dispersed SiO2 thin films, satisfies criteria
      including high uniformity, fast switching speed, and long retention for non
      volatile memory application. This resistive element obeys Ohm's law for the area
      dependence, but its resistance exponentially increases with the film thickness,
      which provides new freedom to tailor the device characteristics. 

PMID- 24737181
TI  - [Assessment of the inter- and intraobserver variability for sonographical
      measurement of intestinal wall thickness in dogs without gastrointestinal
      diseases].
AB  - OBJECTIVE: The aim of the present study was to determine inter- and intraobserver
      agreement for transabdominal ultrasonographic measurements of the intestinal wall
      in dogs without gastrointestinal diseases. MATERIAL AND METHODS: This prospective
      study included 30 dogs diagnosed with a non-gastrointestinal disease and were
      evaluated using a transabdominal ultrasound scan in our clinic. Transverse
      ultrasonographic images for each segment (duodenum, jejunum, colon descendens)
      were obtained. These images were masked, randomized and imported as DICOM files
      in the OsiriX(r) version 5.0 program for Mac Os X. Two observers independently
      determined the intestinal wall thicknesses using the software inherent
      measurement tools. The measurements were repeated five times for each segment in
      all patients on 4 consecutive days. Therefore, each observer performed 1800
      measurements, and 3600 measurements in total were analyzed. RESULTS: The mean
      values for each intestinal segment were comparable to those in the literature.
      The statistical analyses showed a significant positive correlation (p  <  0.01)
      for the inter- and intraobserver measurements at all intestinal locations. There
      was very high intraobserver repeatability for the measurements, with deviations
      of <  10%. In addition, the study displayed good interobserver reproducibility
      for the measurements of all intestinal segments, with variances of <  20% for the
      duodenum and jejunum, and <  50% for the colonic wall thickness. Even with these
      variances the interobserver variability for all segments was much less than the
      mean deviance between normal and diseased dogs. CONCLUSION AND CLINICAL
      RELEVANCE: Transabdominal ultrasonography is a practicable tool to assess
      intestinal wall thickness and integrity in small animal medicine. Our results are
      comparable to established reference ranges for the normal canine intestinal wall
      thickness. In addition, we found a good inter- and intraobserver agreement for
      the measurements of the canine wall thicknesses in dogs without gastrointestinal
      diseases.

PMID- 24737182
TI  - In vitro biomechanical comparison of a newly designed interlocking nail system to
      a standard DCP. Testing of cat femora in an osteotomy gap model.
AB  - OBJECTIVE: To describe a newly designed interlocking nail system (Targon(r) Vet
      System, TVS) tested in a model of diaphyseal femoral fractures in cats. MATERIAL
      AND METHODS: Introduction of the TVS and presentation of the system components.
      Evaluation of application range and biomechanical testing of the TVS in cadaver
      bones under cyclic loading until fatigue failure occurred. The first two test
      groups compared the influence of implantation and immediate removal of the TVS
      locking bolts and six holes created by 2.0 mm cortical screws on the stability of
      feline femora. In the third group the two fixation systems were compared to each
      other with implants in place in an osteotomy gap model. The failure mode was
      statistically compared for each group (p < 0.05). RESULTS: Femora after
      implantation and removal of the bolts of the TVS were significantly stiffer than
      after implantation and removal of the six 2.0 mm cortical screws. In the
      osteotomy gap model, femora with the TVS in place failed some- what later, but
      not statistically significant, than the opposite femur of the same cat with the
      2.0 8-hole DCP in place. CONCLUSION AND CLINICAL RELEVANCE: Using this testing
      method, stability of the TVS seems to be biomechanically comparable to
      conventional osteosynthesis plate systems. Therefore the TVS may be an
      encouraging alternative to conventional osteosynthesis systems in diaphyseal
      fractures, offering several advantages without the need for extensive specialized
      equipment.

PMID- 24737183
TI  - [The intervertebral vacuum phenomenon as a computed-tomographic finding in the
      dog and its significance as an indicator for surgical treatment of vertebral disc
      herniations].
AB  - OBJECTIVE: The intervertebral vacuum phenomenon (VP) in the dog describes an
      accumulation of gas in the intervertebral disc space. It occurs primarily after
      vaporization of solute gases in the extracellular fluids in fissures of
      degenerative vertebral discs but can also arise following a sudden fall in
      pressure, for example, after a vertebral disc herniation. VPs are detectable
      using radiography, computed tomography (CT) and magnetic resonance imaging (MRI).
      Intervertebral VP occurrence is an indication for vertebral disc herniation. The
      aim of this study was to determine the frequency and localization of the VP in
      intervertebral disc spaces of dogs and further to correlate the incidence of
      intervertebral VP with vertebral disc herniation indicative for surgical
      treatment. MATERIAL AND METHODS: We evaluated CT-studies of the vertebral column
      of dogs presented at the clinic between January 2007 and June 2012 (n = 693). In
      total, 529 cases fulfilled the inclusion criterion of a CT-study of the vertebral
      column from the first thoracic vertebra to the first sacral vertebra in the soft
      tissue and bone windows. The evaluation included an inter-observer comparison
      between observers with and without practical experience. RESULTS: Observers with
      and without practical experience identified intervertebral VP in 5.7% and 6.8% of
      the dogs, respectively, with a mean age of 7.7 +/- 2.9 years and 7.3 +/- 3.1
      years, respectively. More male than female dogs were affected. In total, 66.7%
      and 63.9% of the dogs with VP, respectively, received surgical treatment of the
      vertebral column. The surgical site correlated with the location of the
      intervertebral VP in 55.0% and 65.2% of cases, respectively. CONCLUSION AND
      CLINICAL RELEVANCE: Although intervertebral VP can indicate vertebral disc
      degeneration and herniation, it should not be considered a unique identifier.
      Localization for surgery should be based on clinical symptoms and CT- and/or MRI
      findings showing vertebral disc herniation or compression of the spinal cord.
      Practical experience is unnecessary to detect an intervertebral VP.

PMID- 24737184
TI  - Incidence of delayed hair re-growth, pruritus, and urinary retention after
      epidural anaesthesia in dogs.
AB  - OBJECTIVE: Delayed hair re-growth, pruritus and urinary retention are known
      complications after epidural anaesthesia in dogs. The aim of this study was to
      prospectively evaluate the effect of epidurally administered drugs on the
      occurrence of these complications in dogs. MATERIAL AND METHODS: Ninety dogs were
      included in this study. Eighty client-owned dogs undergoing surgery were randomly
      assigned to one of three epidural treatment groups: either morphine and
      bupivacaine (MB), bupivacaine (B), or saline solution 0.9% (S) was administered
      epidurally to these patients. Ten dogs were only clipped in the lumbosacral area
      (C). Follow-up started 4 weeks after clipping and was performed every 4-5 weeks
      in cases of delayed hair re-growth or pruritus. Hair re-growth in the lumbosacral
      area was observed and compared to hair re-growth in the surgical field and the
      fentanyl patch area. Cytological analysis and a trichogram were performed if hair
      re-growth was delayed after 6 months. Time interval to first urination
      postoperatively was recorded (n = 80). RESULTS: Hair re-growth was delayed in 11
      dogs (12.2%; B: n = 7, S: n = 2, MB: n = 1, C: n = 1) with no differences between
      groups. Pruritus was evident in two dogs (2.2%; MB: n = 1, S: n = 1). After 6
      months, hair had started to re-grow in all but one dog (B). After 10 months the
      coat of this dog had re-grown. Time to first urination did not differ between
      groups. CONCLUSION AND CLINICAL RELEVANCE: No direct correlation between the
      particular drugs injected epidurally and delayed hair re-growth, pruritus and
      urinary retention could be shown. Dog owners should be informed that hair re
      growth after epidural anaesthesia could be markedly delayed.

PMID- 24737185
TI  - [Hygienic quality of feedstuffs for small mammals sent to the consultation
      service].
AB  - OBJECTIVE: Evaluation of the hygienic status of feedstuffs for small mammals,
      including rabbits, guinea pigs and chinchilla, kept as pets. MATERIAL AND
      METHODS: A total of 356 feedstuffs that had been sent to the consulting service
      of the institute with a usable case history between January 2000 and April 2011
      were analysed by sensory testing and microbiological examination. The
      interpretation of the microbiological results was performed with regard to
      benchmarks given by the working group "feed microbiology of section VI of the
      VDLUFA" for hay, straw and further feedstuffs. RESULTS: Within the sensory
      evaluation, the parameters "texture" (indicating the moisture content of a feed)
      and "smell" (mouldy or yeasty nuances) provided the first important information
      on feed quality. Deviations in these parameters were observed in 29.0% and 41.2%,
      respectively, of the analysed roughages and in 27.4% and 15.1% of mixed feeds,
      respectively. In about 10% of the feeds, pests (mites, Psocoptera as an indicator
      of mould infestation) were diagnosed microscopically. Using the differentiation
      of the germs as described above, faults in the hygienic quality could be detected
      mainly in roughage (hay, straw) and the so-called coloured feed (mixed feed based
      on ingredients including oat, barley or corn) whereas they occurred rarely in
      commercial pelleted mixed feeds based on green meal. CONCLUSION AND CLINICAL
      RELEVANCE: In cases of hygienic deficits in feedstuffs, it was often unclear
      whether the reduced hygienic quality resulted from the production conditions
      (i.e. in the factory) or by improper storage of the feedstuffs by traders or pet
      owners. A general recommendation should be given to the owner to check the feed
      using a critical sensory evaluation to avoid health disorders in pets due to
      higher levels of germs or poisonous plants.

PMID- 24737186
TI  - [Magnetic resonance imaging features of a caudal cruciate ligament rupture
      associated with a suspected bone bruise lesion in a dog].
AB  - In this case study we describe a surgically confirmed caudal cruciate ligament
      rupture in a 10-year-old Border Collie. Magnetic resonance imaging (MRI)
      demonstrated a complete rupture of the caudal cruciate ligament, a suspected bone
      bruise lesion on the proximolateral tibia and a muscle strain injury of the M.
      flexor digitorum lateralis. In human medicine, bone bruise lesions in MRI have
      been described as "footprint injuries" and can thereby explain the mechanism of
      trauma in ligament injuries. The combination of the MRI findings in this case can
      help to understand how the rarely diagnosed isolated rupture of the caudal
      cruciate ligament occurred in this dog. 

PMID- 24737187
TI  - [Methylphenidate use in dogs with attention deficit hyperactivity disorder
      (ADHD). A case report of a Weimaraner bitch].
AB  - A 10-month-old Weimaraner bitch was presented at the practice exhibiting
      agitation, hyperactivity, inability to learn and attention deficit. The
      diagnostic findings were excessive, long-lasting acoustic and locomotory activity
      with unexpected inappropriate reactions. Hematological and biochemical blood
      analyses did not demonstrate abnormal findings. The first attempts at behavioral
      therapy and fluoxetine application were unsatisfactory. Therefore, a test was
      conducted with medication for central nervous system stimulation to confirm a
      diagnosis of hyperkinesis. Following the diagnosis of attention deficit
      hyperactivity disorder, the therapy was continued with behavioral modifications,
      with special consideration of rehabituation and resocialization as well as the
      use of methylphenidate. During the course of the therapy the bitch developed
      hyperactivity again when on heat. After changing the dosage of methylphenidate
      and additionally using dog appeasing pheromone, the behavior of the bitch became
      normal after 8 days. Two months later endoscopic ovarioectomy was performed.
      Twelve months after the initial use of methylphenidate the medication could be
      discontinued completely and the dog's behavior was normal. The methylphenidate
      dosage used during this therapy was much higher than recommended in the
      literature.

PMID- 24737188
TI  - [Necrotizing fasciitis: a review].
AB  - Necrotizing fasciitis is a rare, fatal bacterial infection associated with a high
      morbidity in humans (25-40%) that is frequently underdiagnosed in veterinary
      patients. Rapid diagnosis of the disease is mandatory because the time to
      surgical intervention and the degree of debridement are the only predictive
      variables that influence a successful outcome. Specific clinical signs are not
      always present, which makes an accurate diagnosis difficult. Despite differences
      in microbiological etiology, the disease pattern is comparable between canine,
      feline and human cases. Based on the current literature and our own experience,
      this article presents a review of the etiology, pathophysiology, diagnostic
      strategies, therapy and prognosis of the disease. 

PMID- 24737190
TI  - Lithiated primary amine--a new material for hydrogen storage.
AB  - A facile method for synthesizing crystalline lithiated amines by ball milling
      primary amines with LiH was developed. The lithiated amines exhibit an
      unprecedented endothermic dehydrogenation feature in the temperature range of 150
      250  degrees C, which shows potential as a new type of hydrogen storage material.
      Structural analysis and mechanistic studies on lithiated ethylenediamine (Li2EDA)
      indicates that Li may mediate the dehydrogenation through an alpha,beta-LiH
      elimination mechanism, creating a more energy favorable pathway for the selective
      H2 release.

PMID- 24737189
TI  - Do patient and ward-related characteristics influence the use of coercive
      measures? Results from the EUNOMIA international study.
AB  - PURPOSE: This study aims to identify whether selected patient and ward-related
      factors are associated with the use of coercive measures. Data were collected as
      part of the EUNOMIA international collaborative study on the use of coercive
      measures in ten European countries. METHODS: Involuntarily admitted patients (N =
      2,027) were divided into two groups. The first group (N = 770) included patients
      that had been subject to at least one of these coercive measures during
      hospitalization: restraint, and/or seclusion, and/or forced medication; the other
      group (N = 1,257) included patients who had not received any coercive measure
      during hospitalization. To identify predictors of use of coercive measures, both
      patients' sociodemographic and clinical characteristics and centre-related
      characteristics were tested in a multivariate logistic regression model,
      controlled for countries' effect. RESULTS: The frequency of the use of coercive
      measures varied significantly across countries, being higher in Poland, Italy and
      Greece. Patients who received coercive measures were more frequently male and
      with a diagnosis of psychotic disorder (F20-F29). According to the regression
      model, patients with higher levels of psychotic and hostility symptoms, and of
      perceived coercion had a higher risk to be coerced at admission. Controlling for
      countries' effect, the risk of being coerced was higher in Poland. Patients'
      sociodemographic characteristics and ward-related factors were not identifying as
      possible predictors because they did not enter the model. CONCLUSIONS: The use of
      coercive measures varied significantly in the participating countries. Clinical
      factors, such as high levels of psychotic symptoms and high levels of perceived
      coercion at admission were associated with the use of coercive measures, when
      controlling for countries' effect. These factors should be taken into
      consideration by programs aimed at reducing the use of coercive measures in
      psychiatric wards.

PMID- 24737191
TI  - Local venous thrombotic risk of an expanding haemostatic agent used during liver
      resection.
AB  - BACKGROUND: For patients undergoing liver resection that leaves an empty
      intraparenchymal cavity, traditional topical agents might be inadequate to
      achieve additional hemostasis. A new hemostatic expanding topical foam
      (BioFoam((r))) has been designed to provide a mechanical seal. The objective of
      this study was to report our preliminary results regarding the safety and the
      efficacy using this foam. METHODS: Between 2009 and 2011, BioFoam((r)) was used
      to fill a three-dimensional defect following liver resection in 14 patients. The
      operative results and postoperative course of these patients were compared to
      those of 14 matched controls who underwent liver resection but did not receive
      BioFoam((r)). RESULTS: The two groups were similar in terms of demographics,
      indications for liver resection, type of surgical procedure, and type and
      duration of clamping. BioFoam((r)) patients experienced significantly less
      operative blood loss (275 vs. 630 ml, p = 0.032) but similar operative
      transfusion rates (28.6 vs. 35.7 %, p = 0.686) compared to no-BioFoam((r))
      patients. The postoperative mortality was nil and no patient developed
      postoperative hemorrhage. While the two groups shared similar overall (64.3 vs.
      57.1 %, p = 0.599) and major (28.6 vs. 14.3 %, p = 0.357) complications rates,
      BioFoam((r)) patients experienced significantly higher major vascular thrombosis
      compared to no-BioFoam((r)) patients (29 vs. 0 %, p = 0.04). In the BioFoam((r))
      group, major vascular thrombosis was associated with exposure of the vessel along
      the transection plane. CONCLUSION: While the clinical benefit of BioFoam((r)) in
      high-risk liver resections leaving a deep parenchymal defect remains to be
      proven, the associated risk of vascular thrombosis should preclude its use in
      contact with major veins.

PMID- 24737192
TI  - Prioritizing the expenses of breast cancer treatment makes sense- not just in
      developing countries, but across the globe.

PMID- 24737193
TI  - miR-20a is an independent prognostic factor in colorectal cancer and is involved
      in cell metastasis.
AB  - Accumulating evidence indicates that dysregulated microRNAs (miRNAs) are involved
      in cancer development, progression and metastasis. miR-20a was found to be
      involved in invasion and epithelial-mesenchymal transition (EMT) programs, with
      its aberrant expression having been observed in a variety of malignant tumors.
      However, the molecular mechanisms underlying the role of miR-20a in colorectal
      cancer (CRC) development remain to be fully elucidated. In the present study, the
      expression of miR-20a was compared between CRC tissue samples and the normal
      adjacent mucosa using quantitative polymerase chain reaction. The association of
      miR-20a expression with clinicopathological characteristics was assessed using
      appropriate statistical analysis. The migration and invasion of SW480 cells was
      examined following transfection of the cells with either miR-20a precursor or a
      negative control miRNA precursor. The effect of miR-20a on the EMT in CRC cells
      in vitro was also analyzed. The regulatory effect of miR-20a on SMAD family
      member 4 (SMAD4) was evaluated using a dual-luciferase reporter assay. Relative
      expression levels of miR-20a were significantly higher in CRC tissue than those
      in the normal adjacent mucosa, and high expression of miR-20a correlated with
      lymph node metastases and distant metastases. Kaplan-Meier analysis indicated
      that patients with increased miR-20a levels exhibited unfavorable overall
      survival. Furthermore, multivariate analysis showed that miR-20a was an
      independent prognostic factor. The transfection of SW480 CRC cells with miR-20a
      promoted migration and invasion in vitro, and the upregulation of miR-20a induced
      EMT in CRC cells. An inverse correlation between the levels of miR-20a and SMAD4
      was observed in patients with CRC. Overexpression of miR-20a in CRC cells
      decreased SMAD4 expression and decreased SMAD4-driven luciferase reporter
      activity. The present study revealed that miR-20a was an independent prognostic
      factor in CRC. Furthermore, miR-20a induced EMT and regulated migration and
      invasion of SW480 cells, at least in part via suppression of SMAD4 expression.
      The present study suggests that miR-20a may serve as a novel prognostic marker
      and therapeutic target for CRC. 

PMID- 24737194
TI  - Ibn al-Haytham (965-1039 AD), the original portrayal of the modern theory of
      vision.
AB  - Abu ?Ali al-Hasan ibn al-Hasan ibn al-Haytham, known in the West as Alhazen, was
      an Arab-Islamic scholar who helped develop the science of ophthalmology during
      the medieval era. He was the first to reject firmly the extramission theory of
      vision, which was prevalent during his time, and suggested that the eyes are the
      source of the light rays responsible for vision. Ibn al-Haytham in his book
      entitled Kitab al-Manazir (Book of Optics) explained vision based on light
      emanating from objects. In this study we review Ibn al-Haytham's life and
      introduce his major contribution to the field of ophthalmology, his theory of
      vision. 

PMID- 24737195
TI  - President Franklin D Roosevelt (1882-1945) and Doctor Frank Howard Lahey's (1880
      1953) dilemma: The complexities of medical confidentiality with World Leaders.
AB  - In the months before the Presidential Election of November 1944, there were
      serious concerns about the health of President Franklin D Roosevelt. He had lost
      considerable weight and his once robust appearance had given way to a tired and
      haggard look. Despite these worrisome observations, Vice-Admiral Ross T McIntire,
      who served as Franklin Roosevelt's personal physician from 1933 until Roosevelt's
      death, lied when he proclaimed Roosevelt to be in 'excellent condition for a man
      of his age'. The truth about Roosevelt's health was further obscured when
      Roosevelt's medical records disappeared. 

PMID- 24737196
TI  - Stanley Cobb (1887-1968): studying the link between the mind and the body.
AB  - Stanley Cobb was an eminent neurologist that is regarded as 'the founder of
      biological psychiatry'. Having studied at Harvard university, Cobb had many
      varied interests, including ornithology and natural history. Following his
      undergraduate studies, he travelled widely and incorporated a period of study in
      Europe. Upon return to America, he was appointed Director of the Harvard
      Neurological Unit. Following a change of interest from neurology to psychiatry,
      Cobb was instrumental in establishing psychiatry as a specialty in America. The
      research laboratory, 'Stanley Cobb Laboratory for Psychiatric Research' at
      Massachusetts General Hospital was named in his honour and contribution to the
      service at the hospital. 

PMID- 24737197
TI  - Alexis Carrel (1873-1944): visionary vascular surgeon and pioneer in organ
      transplantation.
AB  - Alexis Carrel was a French surgeon in the 20th century. He made significant
      contributions to many advances in the fields of vascular surgery, cardiothoracic
      surgery and organ transplantation. He demonstrated that blood vessels can be
      united end-to-end and pioneered the triangulation suturing technique in vascular
      anastomosis. The methods he developed are still in use to this day. He insisted
      on the importance of absolute asepsis in vascular surgery when such practices
      were almost unheard of. He was also considered the father of solid organ
      transplantation. He was awarded the Nobel Prize in recognition of his work.
      Together with Charles Lindbergh, he developed the extracorporeal perfusion pump
      to keep organs alive outside the human body. His contribution to medicine also
      extended to tissue culture and wound management. He was one of the most
      controversial figures of his generation, believing in the idea of genetic
      superiority and eugenics and he was associated with fascism in the 1930s. 

PMID- 24737198
TI  - Long-term effects of repetitive transcranial magnetic stimulation in unilateral
      tinnitus.
AB  - OBJECTIVES/HYPOTHESIS: We investigated the long-term effects of repetitive
      transcranial magnetic stimulation (rTMS) delivered to the temporoparietal
      junction and compared contralateral and ipsilateral application in patients with
      unilateral tinnitus. STUDY DESIGN: Prospective study. METHODS: A total of 61
      patients with asymmetric hearing loss and nonpulsatile chronic tinnitus localized
      to the poorer ear who were refractory to medical treatment were enrolled.
      Patients were randomly assigned to one of two treatment groups: 1-Hz stimulation
      applied to the temporoparietal junction either ipsilaterally (n = 30) or
      contralaterally (n = 31) to the symptomatic ear. Changes in the Tinnitus Handicap
      Inventory (THI) scores and self-rating visual analog scores (VAS) for loudness,
      awareness, and annoyance were analyzed before and after treatment for 6 months.
      Improved patients were defined as those with decreases in their THI scores by >10
      points and 20%. RESULTS: There were no major complications or worsening of
      hearing. When analyzing the THI scores and VAS pre-rTMS and 6 months after rTMS,
      significant decreases were observed in patients overall (P < .001). For the
      comparison of long-term outcomes between the ipsilateral and contralateral
      stimulation groups, there were no differences in the degree of decrease in THI
      scores or VAS (P > .05). In addition, there was no significant difference in the
      rate of patients who improved between the ipsilateral (14 of 30) and
      contralateral (16 of 31) stimulation groups (P = .800). The ipsilateral group
      showed a more rapid improvement than the contralateral group. CONCLUSIONS: Daily
      application of 1-Hz rTMS to the temporoparietal area is safe and has long-term
      beneficial effects. The laterality of stimulation is not the decisive factor.

PMID- 24737200
TI  - Serum enhanced cytokine responses of macrophages to silica and iron oxide
      particles and nanomaterials: a comparison of serum to lung lining fluid and
      albumin dispersions.
AB  - The potential hazard to humans exposed to nanomaterials such as silica and iron
      oxide was investigated using an in vitro macrophage cell culture system.
      Amorphous silica and iron oxide particles and nanomaterials (NMs) were dispersed
      in cell culture medium supplemented with either bovine serum albumin (BSA), lung
      lining fluid (LLF) or serum, in order to mimic the body fluids encountered during
      different routes of exposure in the body. End points investigated included
      macrophage viability and cytokine production. Silica NMs and particles (50 and
      200 nm, respectively) were unmodified (plain) or aminated (NH2 ). Iron oxide NMs
      and particles, Fe3 O4 45 nm and Fe2 O3 280 nm were also used in this study.
      Silica particles and NMs induced a dose-dependent increase in cytotoxicity as
      measured by lactate dehydrogenase (LDH) release. Serum enhanced silica-induced
      interleukin (IL)-6, IL-10, IL-1beta and MCP-1 release, whereas albumin partially
      inhibited MCP-1 release. Aminated silica, 50 nm was more potent than the 200-nm
      particles at inducing monocyte chemoattractant protein-1 (MCP-1) production when
      dispersed in medium or LLF, suggesting a size specific effect for these particles
      and this cytokine. Iron oxide particles were relatively inert compared with the
      silica particles and NMs; however, serum and albumin did affect cytokine release
      in some treatments. In conclusion, the data suggests that serum, compared with
      medium, BSA and LLF is very potent at enhancing macrophage responses to silica
      and iron oxide particles and NMs. Size was only influential in LLF for a limited
      number of parameters, whereas surface chemistry was not of consequence in this in
      vitro macrophage system.

PMID- 24737199
TI  - Associations between circulating 1,25(OH)2D concentration and odds of
      metachronous colorectal adenoma.
AB  - Cellular-level studies demonstrate that the availability of the secosteroid
      hormone 1alpha,25-dihydroxyvitamin D [1,25(OH)2D] to colon cells promotes anti
      carcinogenic activities. Although epidemiological data are relatively sparse,
      suggestive inverse trends have been reported between circulating 1,25(OH)2D
      concentration and colorectal neoplasia. We therefore sought to evaluate the
      relationship between circulating 1,25(OH)2D concentrations and odds for
      metachronous colorectal adenomas among 1,151 participants from a randomized trial
      of ursodeoxycholic acid for colorectal adenoma prevention. No relationship
      between 1,25(OH)2D and overall odds for metachronous lesions was observed, with
      ORs (95% CIs) of 0.80 (0.60-1.07) and 0.81 (0.60-1.10) for participants in the
      second and third tertiles, respectively, compared with those in the lowest (p
      trend = 0.17). However, a statistically significant inverse association was
      observed between circulating 1,25(OH)2D concentration and odds of proximal
      metachronous adenoma, with an OR (95% CI) of 0.71 (0.52-0.98) for individuals in
      the highest tertile of 1,25(OH)2D compared with those in the lowest (p-trend =
      0.04). While there was no relationship overall between 1,25(OH)2D and
      metachronous distal lesions, there was a significantly reduced odds for women,
      but not men, in the highest 1,25(OH)2D tertile compared with the lowest (OR 0.53;
      95% CI 0.27-1.03; p-trend = 0.05; p-interaction = 0.08). The observed differences
      in associations with proximal and distal adenomas could indicate that delivery
      and activity of vitamin D metabolites in different anatomic sites in the
      colorectum varies, particularly by gender. These results identify novel
      associations between 1,25(OH)2D and metachronous proximal and distal colorectal
      adenoma, and suggest that future studies are needed to ascertain potential
      mechanistic differences in 1,25(OH)2D action in the colorectum.

PMID- 24737201
TI  - Overexpression of fibulin-4 is associated with tumor progression and poor
      prognosis in patients with cervical carcinoma.
AB  - Fibulin-4, a member of the fibulin family of extracellular glycoproteins, is
      implicated in the progression of a number of types of cancer. However, the
      function of fibulin-4 in cervical cancer progression remains unexplored. Fibulin
      4 mRNA and protein expression levels in normal cervical tissue, cervical
      intraepithelial neoplasia (CIN), cervical carcinoma, highly invasive subclones
      and low-invasive subclones were evaluated by real-time reverse transcriptase
      polymerase chain reaction and immunohistochemistry. Serum fibulin-4 levels in
      patients with CIN and cervical carcinoma were measured by enzyme-linked
      immunosorbent assay. To assess the angiogenic properties of fibulin-4, vascular
      endothelial growth factor (VEGF) expression and tumor microvessel density (MVD)
      were analyzed in the cervical carcinoma cases by immunohistochemistry. Fibulin-4
      expression was upregulated in the cervical carcinoma cases, and was positively
      correlated with MVD and VEGF expression. Fibulin-4 overexpression and high serum
      levels were significantly associated with advanced stage, low differentiation,
      lymph node metastasis, and poor prognosis in patients with cervical cancer.
      Fibulin-4 expression was also found to be overexpressed in highly invasive
      subclones when compared with the low-invasive subclones. Fibulin-4 is a newly
      identified glycoprotein that is overexpressed in cervical carcinoma. Fibulin-4
      promotes angiogenesis and is associated with poor prognostic clinicopathologic
      features. This study demonstrated that fibulin-4 may serve as a new prognostic
      factor and as a potential therapeutic target for patients with cervical
      carcinoma. 

PMID- 24737202
TI  - A hundred years of latency: from Freudian psychosexual theory to dynamic systems
      nonlinear development in middle childhood.
AB  - A focus on the latency phase is used to illustrate how theory and developmental
      research have influenced our psychoanalytic views of development over the past
      hundred years. Beginning with Freud's psychosexual theory and his conception of
      latency, an historical overview of the major psychoanalytic contributions bearing
      on this developmental period over the past century is presented. Recent
      longitudinal research in latency supports a nonlinear dynamic systems approach to
      development. This approach obliges us to reconsider our linear theories and how
      we think about and work with our patients. 

PMID- 24737203
TI  - Truth.
AB  - What exactly do we mean by truth? Although the concept is nebulous across the
      array of theoretical perspectives in psychoanalysis, it is fundamental to all
      discourses. Is psychoanalysis in a position to offer a theory of truth despite
      the fact that at present it has no explicit, formal theory regarding the matter?
      A general metatheory is proposed here that allows for discrete categories and
      instantiations of truth as metacontextual appearance. In revisiting the ancient
      notion of aletheia as disclosedness or unconcealment, we may discover a distinct
      psychoanalytic contribution to truth conditioned on unconscious processes
      reappropriated from Heidegger's project of fundamental ontology. Construed as a
      dialectics of truth, this notion accords well with how psychoanalysts understand
      the dynamic unconscious and how it functions to both reveal and conceal. Given
      that clinical experience demonstrates the workings of dynamic unconscious
      activity, psychoanalytic theory may contribute a vocabulary relevant to
      philosophy by explicating the motives and mechanisms that create the appearances
      of contextual truth as such, phenomena whose causes have previously gone
      undescribed. 

PMID- 24737204
TI  - Coming to terms with intersubjectivity: keeping language in mind.
AB  - Recent reports of clinical experiences, from multiple theoretical perspectives
      using different terminologies, converge on the topic of the origin and nature of
      intersubjectivity as it emerges in clinical interactions. Intersubjectivity is
      explored from the point of view of language and communication, and the
      distinctive properties of language that create a shared intrapsychic world, on
      which intersubjectivity subtends, are discussed. This viewpoint can explain
      behavior and pathologies that arise from the struggle to maintain one's personal
      subjectivity in an intersubjective world. Understanding the role and functions of
      language may also illuminate the therapeutic benefits of talk-based therapies. 

PMID- 24737205
TI  - Panel report. Mourning, identity, creativity.

PMID- 24737213
TI  - Endocrinology and art. Winthrop Chandler "Concealing Enlarged Thyroid" (6 April
      1747 - 9 July 1790): National Gallery of Art, Washington DC.

PMID- 24737214
TI  - The role of hip and chest radiographs in osteoporotic evaluation among south
      Indian women population: a comparative scenario with DXA.
AB  - BACKGROUND: Osteoporosis is recognized as a worldwide skeletal disorder problem.
      In India, the older as well as postmenopausal women population suffering from
      osteoporotic fractures has been a common issue. Bone mineral density measurements
      gauged by dual-energy X-ray absorptiometry (DXA) are used in the diagnosis of
      osteoporosis. OBJECTIVES: (1) To evaluate osteoporosis in south Indian women by
      radiogrammetric method in a comparative perspective with DXA. (2) To assess the
      capability of KJH; Anburajan's Empirical formula in the prediction of total hip
      bone mineral density (T.BMD) with estimated Hologic T.BMD. METHODS: In this cross
      sectional design, 56 south Indian women were evaluated. These women were randomly
      selected from a health camp. The patients with secondary bone diseases were
      excluded. The standard protocol was followed in acquiring BMD of the right
      proximal femur by DPX Prodigy (DXA Scanner, GE-Lunar Corp., USA). The measured
      Lunar Total hip BMD was converted into estimated Hologic Total hip BMD. In
      addition, the studied population underwent chest and hip radiographic
      measurements. Combined cortical thickness of clavicle has been used in KJH;
      Anburajan's Empirical formula to predict T.BMD and compared with estimated
      Hologic T.BMD by DXA. RESULTS: The correlation coefficients exhibited high
      significance. The combined cortical thickness of clavicle and femur shaft of
      total studied population was strongly correlated with DXA femur T.BMD
      measurements (r = 0.87, P < 0.01 and r = 0.45, P < 0.01) and it is also having
      strong correlation with low bone mass group (r = 0.87, P < 0.01 and r = 0.67, P <
      0.01) KJH; Anburajan's Empirical formula shows significant correlation with
      estimated Hologic T.BMD (r = 0.88, P < 0.01) in total studied population. The
      empirical formula was identified as better tool for predicting osteoporosis in
      total population and old-aged population with a sensitivity (88.8 and 95.6 %),
      specificity (89.6 and 90.9 %), positive predictive value (88.8 and 95.6 %) and
      negative predictive value (89.6 and 90.9 %), respectively. CONCLUSION: The
      results suggest that combined cortical thickness of clavicle and femur shaft
      using radiogrammetric method is significantly correlated with DXA. Moreover, KJH;
      Anburajan's Empirical formula is useful and better index than other simple
      radiogrammetry measurements in the evaluation of osteoporosis from the economical
      and widely available digital radiographs.

PMID- 24737215
TI  - Manganese(IV)-mediated hydroperoxyarylation of alkenes with aryl hydrazines and
      dioxygen from air.
AB  - We report a new carbooxygenation-type version of the Meerwein arylation in which
      the introduction of oxygen is achieved by using dioxygen from the air. In this
      way, hydroperoxides were obtained from activated as well as non-activated alkenes
      by oxidizing aryl hydrazines with manganese dioxide. The best results were
      obtained with alpha-substituted acrylates. Importantly, the aryl hydrazine has to
      be added slowly to the reaction mixture to allow sufficient uptake of dioxygen
      from the air. Competition and labeling experiments revealed hydroperoxyl radicals
      as novel oxygen-centered radical scavengers. 

PMID- 24737217
TI  - Implementing hospital innovation in Taiwan: the perspectives of institutional
      theory and social capital.
AB  - The main purpose of this study is to develop an innovation model for hospital
      organisations. For this purpose, this study explores and examines the
      determinants, capabilities and performance in the hospital sector. First, this
      discusses three categories of determinants that affect hospitals' innovative
      capability studies: (1) knowledge stock; (2) social ties; and (3) institutional
      pressures. Then, this study examines the idea of innovative hospital
      capabilities, defined as the ability of the hospital organisation to innovate
      their knowledge. Finally, the hospital evaluation rating, which identifies
      performance in the hospital sector, was examined. This study empirically tested
      the theoretical model at the organisation level. The findings suggest that a
      hospital's innovative capabilities are influenced by its knowledge stock, social
      ties, institutional pressures and the impact of hospital performance. However, in
      attempts to keep hospitals aligned with their highly institutionalised
      environments, it may prove necessary for hospital administrators to pay more
      attention to both existing knowledge stock and the process of innovation if the
      institutions are to survive. Finally, implications for theory and practitioners
      complete this study.

PMID- 24737216
TI  - [Secondary telangiectatic osteosarcoma of the left femur. A case presentation of
      an unusual course of disease].
AB  - BACKGROUND: This article presents the unusual case of a 73-year-old male patient
      who was treated with primary interlocking nailing after a pathological femoral
      fracture. DIAGNOSTICS: Despite comprehensive diagnostics including several
      biopsies, a tumor could not be detected. In 2008 when progressive cystic femoral
      destruction leading to loosening of the nail necessitated a partial femoral
      prosthesis, an osteosarcoma could first be diagnosed in the resected bone.
      THERAPY: Advanced progression of the tumor required an extended hip
      exarticulation. During the current restaging of the now 84-year-old patient no
      tumor could be detected. CONCLUSION: When a malignancy cannot be excluded even by
      repeated biopsies of radiologically suspicious structures, an adequate tumor
      staging followed by close monitoring should be carried out. For a clinically
      silent, long-term course of cystic destruction of a long bone over several years,
      an age over 60 years and a lack of distant metastases, an atypical osteosarcoma
      should be considered in the differential diagnosis.

PMID- 24737218
TI  - Cyanoborohydride-based ionic liquids as green aerospace bipropellant fuels.
AB  - In propellant systems, the most common bipropellants are composed of two
      chemicals, a fuel (or reducer) and an oxidizer. Currently, the choices for
      propellant fuels rely mainly on hydrazine and its methylated derivatives, even
      though they are extremely toxic, highly volatile, sensitive to adiabatic
      compression (risk of detonation), and, therefore, difficult to handle. With this
      background, the search for alternative green propellant fuels has been an urgent
      goal of space science. In this study, a new family of cyanoborohydride-based
      ionic liquids (ILs) with properties and performances comparable to hydrazine
      derivatives were designed and synthesized. These new ILs as bipropellant fuels,
      have some unique advantages including negligible vapor pressure, ultra-short
      ignition delay (ID) time, and reduced synthetic and storage costs, thereby
      showing great application potential as environmentally friendly fuels in
      bipropellant formulations. 

PMID- 24737220
TI  - In-plane thermal conductivity of sub-20 nm thick suspended mono-crystalline Si
      layers.
AB  - We measure the thermal conductivity of a 17.5-nm-thick single crystalline Si
      layer by using a suspended structure developed from a silicon-on-insulator wafer,
      in which the Si layer bridges the suspended platforms. The obtained value of 19
      Wm(-1) K(-1) at room temperature represents a tenfold reduction with respect to
      bulk Si. This design paves the way for subsequent lateral nanostructuration of
      the layer with lithographic techniques, to define different geometries such as Si
      nanowires, nanostrips or phononic grids. As a proof of concept, nanostrips of 0.5
      * 10 MUm have been defined by focused ion beam (FIB) in the ultrathin Si layer.
      After the FIB cutting process with Ga ions at 30 kV and 100 pA, the measured
      thermal conductivity dramatically decreased to 1.7 Wm(-1) K(-1), indicating that
      the structure became severely damaged (amorphous). Re-crystallization of the
      structure was promoted by laser annealing while monitoring the Raman spectra. The
      thermal conductivity of the layer increased again to a value of 9.5 Wm(-1) K(-1)
      at room temperature, below that of the single crystalline material due to phonon
      scattering at the grain boundaries. 

PMID- 24737221
TI  - Psychiatric manifestations as primary symptom of neurosyphilis among HIV-negative
      patients.
AB  - This study characterizes psychiatric manifestations as a primary symptom of
      neurosyphilis (NS). Fifty-two of the 169 NS patients presented with psychiatric
      manifestations, many patients had characteristics of more than one syndrome,
      including cognitive impairment, personality disorders, delirium, hostility,
      dysarthria, confusion, disruption of their sleep-wake cycle, fecal and urinary
      incontinence, dysphoria, paranoia, hallucinations, expansive mood, and mania.
      Fifty-two patients had positive sera RPR and T. pallidum particle agglutination
      (TPPA), 75% had positive CSF RPR, 96.2% had positive CSF TPPA, 44.2% had CSF
      pleocytosis and elevated CSF proteins, and 70.0% had nonspecific, abnormal brain
      MRIs. These results indicate that NS mimics almost all psychiatric disorders. 

PMID- 24737224
TI  - Abstracts from the 37th Annual Meeting of the Society of General Internal
      Medicine, 2014, San Diego, CA, USA.

PMID- 24737223
TI  - Teamwork and delegation in medical homes: primary care staff perspectives in the
      Veterans Health Administration.
AB  - BACKGROUND: The patient-centered medical home (PCMH) relies on a team approach to
      patient care. For organizations engaged in transitioning to a PCMH model,
      identifying and providing the resources needed to promote team functioning is
      essential. OBJECTIVE: To describe team-level resources required to support PCMH
      team functioning within the Veterans Health Administration (VHA), and provide
      insight into how the presence or absence of these resources facilitates or
      impedes within-team delegation. DESIGN: Semi-structured interviews with members
      of pilot teams engaged in PCMH implementation in 77 primary care clinics serving
      over 300,000 patients across two VHA regions covering the Mid-Atlantic and
      Midwest United States. PARTICIPANTS: A purposive sample of 101 core members of
      pilot teams, including 32 primary care providers, 42 registered nurse care
      managers, 15 clinical associates, and 12 clerical associates. APPROACH:
      Investigators from two evaluation sites interviewed frontline primary care staff
      separately, and then collaborated on joint analysis of parallel data to develop a
      broad, comprehensive understanding of global themes impacting team functioning
      and within-team delegation. KEY RESULTS: We describe four themes key to
      understanding how resources at the team level supported ability of primary care
      staff to work as effective, engaged teams. Team-based task delegation was
      facilitated by demarcated boundaries and collective identity; shared goals and
      sense of purpose; mature and open communication characterized by psychological
      safety; and ongoing, intentional role negotiation. CONCLUSIONS: Our findings
      provide a framework for organizations to identify assets already in place to
      support team functioning, as well as areas in need of improvement. For teams
      struggling to make practice changes, our results indicate key areas where they
      may benefit from future support. In addition, this research sheds light on how
      variation in medical home implementation and outcomes may be associated with
      variation in team-based task delegation.

PMID- 24737225
TI  - Making the case for general internal medicine.

PMID- 24737226
TI  - The next steps in competency-based medical education: milestones, entrustable
      professional activities and observable practice activities.

PMID- 24737227
TI  - A fluorescent probe for detecting thiamine using the luminescence intensity of
      nanoparticles.
AB  - Determination of molecules and biomolecules using nanoparticles is promising in
      the development of analytical techniques. Modified Eu-doped Y2O3 nanoparticles
      (Y2O3:Eu NPs) by captopril have been used as a probe for thiamine (vitamin B1)
      determination. According to the fluorescence enhancement of modified Eu-doped
      Y2O3 nanoparticles caused by thiamine, a simple and sensitive method were
      proposed for its detection. The increase in modified Y2O3:Eu NPs fluorescence
      signal as a function of thiamine concentration was found to be linear in the
      concentration range of 0-44 MUM. The limit of detection (LOD) of thiamine by this
      method was 0.144 MUM. All the measurements were performed in natural pH, at the
      room temperature under ambient conditions. Possible interaction mechanism was
      discussed.

PMID- 24737228
TI  - Usefulness of urinary kidney injury molecule-1 (Kim-1) as a biomarker for
      cisplatin-induced sub-chronic kidney injury.
AB  - We explored biomarkers suitable for monitoring sub-chronic kidney injury using
      the three rat models of cisplatin (CDDP)-induced kidney injury, which were
      designed to extend the current knowledge beyond the sub-acute exposure period. In
      the pilot study, a single intravenous administration of 1.5 mg kg(-1) CDDP to
      rats was confirmed to result in no histopathological changes. Subsequently, CDDP
      was intravenously administered to rats at a dose of 1.5 mg kg(-1) for 4 days at
      24-h intervals (Experimental model 1) and for up to 10 weeks at weekly intervals
      (Experimental models 2 and 3), and the changes in blood and urine components,
      such as recently recommended urinary biomarkers (Kim-1, clusterin and so on) and
      traditional blood biomarkers (blood urea nitrogen and serum creatinine), were
      examined together with the histopathological changes in renal tissues during the
      development of the kidney injury in each model. In these experimental models, a
      significant increase in urinary Kim-1 was observed prior to the histopathological
      changes in renal tissues, and these changes were retained after the adverse
      histopathological changes. Significant changes in all of the other urinary
      biomarkers examined occurred along with the histopathological changes. In
      addition, the increase in urinary Kim-1 after weekly treatment with CDDP for 4
      weeks was reduced in a time-dependent manner after cessation of the drug. The
      present findings indicate that urinary Kim-1 is the most useful biomarker for
      CDDP-induced rat sub-chronic kidney injury among the biomarkers examined.

PMID- 24737229
TI  - Introduction to sodium channels.
AB  - Voltage-gated sodium channels (VGSCs) are present in many tissue types within the
      human body including both cardiac and neuronal tissues. Like other channels,
      VGSCs activate, deactivate, and inactivate in response to changes in membrane
      potential. VGSCs also have a similar structure to other channels: 24
      transmembrane segments arranged into four domains that surround a central pore.
      The structure and electrical activity of these channels allows them to create and
      respond to electrical signals in the body. Because of their distribution
      throughout the body, VGSCs are implicated in a variety of diseases including
      epilepsy, cardiac arrhythmias, and neuropathic pain. As such the study of these
      channels is essential. This brief review will introduce sodium channel structure,
      physiology, and pathophysiology. 

PMID- 24737230
TI  - The voltage sensor module in sodium channels.
AB  - The mechanism by which voltage-gated ion channels respond to changes in membrane
      polarization during action potential signaling in excitable cells has been the
      subject of research attention since the original description of voltage-dependent
      sodium and potassium flux in the squid giant axon. The cloning of ion channel
      genes and the identification of point mutations associated with channelopathy
      diseases in muscle and brain has facilitated an electrophysiological approach to
      the study of ion channels. Experimental approaches to the study of voltage gating
      have incorporated the use of thiosulfonate reagents to test accessibility,
      fluorescent probes, and toxins to define domain-specific roles of voltage-sensing
      S4 segments. Crystallography, structural and homology modeling, and molecular
      dynamics simulations have added computational approaches to study the
      relationship of channel structure to function. These approaches have tested
      models of voltage sensor translocation in response to membrane depolarization and
      incorporate the role of negative countercharges in the S1 to S3 segments to
      define our present understanding of the mechanism by which the voltage sensor
      module dictates gating particle permissiveness in excitable cells. 

PMID- 24737231
TI  - Slow inactivation of Na(+) channels.
AB  - Prolonged depolarizing pulses that last seconds to minutes cause slow
      inactivation of Na(+) channels, which regulates neuron and myocyte excitability
      by reducing availability of inward current. In neurons, slow inactivation has
      been linked to memory of previous excitation and in skeletal muscle it ensures
      myocytes are able to contract when K(+) is elevated. The molecular mechanisms
      underlying slow inactivation are unclear even though it has been studied for 50+
      years. This chapter reviews what is known to date regarding the definition,
      measurement, and mechanisms of voltage-gated Na(+) channel slow inactivation. 

PMID- 24737232
TI  - The role of non-pore-forming beta subunits in physiology and pathophysiology of
      voltage-gated sodium channels.
AB  - Voltage-gated sodium channel beta1 and beta2 subunits were discovered as
      auxiliary proteins that co-purify with pore-forming alpha subunits in brain. The
      other family members, beta1B, beta3, and beta4, were identified by homology and
      shown to modulate sodium current in heterologous systems. Work over the past 2
      decades, however, has provided strong evidence that these proteins are not simply
      ancillary ion channel subunits, but are multifunctional signaling proteins in
      their own right, playing both conducting (channel modulatory) and nonconducting
      roles in cell signaling. Here, we discuss evidence that sodium channel beta
      subunits not only regulate sodium channel function and localization but also
      modulate voltage-gated potassium channels. In their nonconducting roles, VGSC
      beta subunits function as immunoglobulin superfamily cell adhesion molecules that
      modulate brain development by influencing cell proliferation and migration, axon
      outgrowth, axonal fasciculation, and neuronal pathfinding. Mutations in genes
      encoding beta subunits are linked to paroxysmal diseases including epilepsy,
      cardiac arrhythmia, and sudden infant death syndrome. Finally, beta subunits may
      be targets for the future development of novel therapeutics. 

PMID- 24737233
TI  - Altered sodium channel gating as molecular basis for pain: contribution of
      activation, inactivation, and resurgent currents.
AB  - Mutations in voltage-gated sodium channels, especially Nav1.7, can cause the
      genetic pain syndromes inherited erythromelalgia, small fiber neuropathy,
      paroxysmal extreme pain disorder, and chronic insensitivity to pain. Functional
      analysis of these mutations offers the possibility of understanding the potential
      pathomechanisms of these disease patterns and also may help to explicate the
      molecular mechanisms underlying pain in normal conditions. The mutations are
      distributed over the whole channel protein, but nevertheless induce similar
      changes for each pain syndrome. In this review we focus on their impact on sodium
      channel gating, which may be conferred via modulation of (1) conformation
      (affecting all gating characteristics); (2) the amount of voltage-sensing charges
      (affecting mainly activation); (3) interaction within the protein (e.g., binding
      of the inactivation linker); and (4) interaction with other proteins (e.g., for
      generation of resurgent currents). Understanding the molecular basis for each
      gating mode and its impact on cellular excitability and nociception in each
      disease type may provide a basis for development of more specific and effective
      therapeutic tools. 

PMID- 24737234
TI  - Regulation/modulation of sensory neuron sodium channels.
AB  - The pseudounipolar sensory neurons of the dorsal root ganglia (DRG) give rise to
      peripheral branches that convert thermal, mechanical, and chemical stimuli into
      electrical signals that are transmitted via central branches to the spinal cord.
      These neurons express unique combinations of tetrodotoxin-sensitive (TTX-S) and
      tetrodotoxin-resistant (TTX-R) Na(+) channels that contribute to the resting
      membrane potential, action potential threshold, and regulate neuronal firing
      frequency. The small-diameter neurons (<25 MUm) isolated from the DRG represent
      the cell bodies of C-fiber nociceptors that express both TTX-S and TTX-R Na(+)
      currents. The large-diameter neurons (>35 MUm) are typically low-threshold A
      fibers that predominately express TTX-S Na(+) currents. Peripheral nerve damage,
      inflammation, and metabolic diseases alter the expression and function of these
      Na(+) channels leading to increases in neuronal excitability and pain. The Na(+)
      channels expressed in these neurons are the target of intracellular signaling
      cascades that regulate the trafficking, cell surface expression, and gating
      properties of these channels. Post-translational regulation of Na(+) channels by
      protein kinases (PKA, PKC, MAPK) alter the expression and function of the
      channels. Injury-induced changes in these signaling pathways have been linked to
      sensory neuron hyperexcitability and pain. This review examines the signaling
      pathways and regulatory mechanisms that modulate the voltage-gated Na(+) channels
      of sensory neurons. 

PMID- 24737236
TI  - Proton modulation of cardiac I Na: a potential arrhythmogenic trigger.
AB  - Voltage-gated sodium (NaV) channels generate the upstroke and mediate duration of
      the ventricular action potential, thus they play a critical role in mediating
      cardiac excitability. Cardiac ischemia triggers extracellular pH to drop as low
      as pH 6.0, within just 10 min of its onset. Heightened proton concentrations
      reduce sodium conductance and alter the gating parameters of the cardiac-specific
      voltage-gated sodium channel, NaV1.5. Most notably, acidosis destabilizes fast
      inactivation, which plays a critical role in regulating action potential
      duration. The changes in NaV1.5 channel gating contribute to cardiac dysfunction
      during ischemia that can cause syncope, cardiac arrhythmia, and even sudden
      cardiac death. Understanding NaV channel modulation by protons is paramount to
      treatment and prevention of the deleterious effects of cardiac ischemia and other
      triggers of cardiac acidosis. 

PMID- 24737237
TI  - Probing gating mechanisms of sodium channels using pore blockers.
AB  - Several classes of small molecules and peptides bind at the central pore of
      voltage-gated sodium channels either from the extracellular or intracellular side
      of the membrane and block ion conduction through the pore. Biophysical studies
      that shed light on the chemical nature, accessibility, and kinetics of binding of
      these naturally occurring and synthetic compounds reveal a wealth of information
      about how these channels gate. Here, we discuss insights into the structural
      underpinnings of gating of the channel pore and its coupling to the voltage
      sensors obtained from pore blockers including site 1 neurotoxins and local
      anesthetics. 

PMID- 24737235
TI  - The role of late I Na in development of cardiac arrhythmias.
AB  - Late I Na is an integral part of the sodium current, which persists long after
      the fast-inactivating component. The magnitude of the late I Na is relatively
      small in all species and in all types of cardiomyocytes as compared with the
      amplitude of the fast sodium current, but it contributes significantly to the
      shape and duration of the action potential. This late component had been shown to
      increase in several acquired or congenital conditions, including hypoxia,
      oxidative stress, and heart failure, or due to mutations in SCN5A, which encodes
      the alpha-subunit of the sodium channel, as well as in channel-interacting
      proteins, including multiple beta subunits and anchoring proteins. Patients with
      enhanced late I Na exhibit the type-3 long QT syndrome (LQT3) characterized by
      high propensity for the life-threatening ventricular arrhythmias, such as Torsade
      de Pointes (TdP), as well as for atrial fibrillation. There are several distinct
      mechanisms of arrhythmogenesis due to abnormal late I Na, including abnormal
      automaticity, early and delayed after depolarization-induced triggered activity,
      and dramatic increase of ventricular dispersion of repolarization. Many local
      anesthetic and antiarrhythmic agents have a higher potency to block late I Na as
      compared with fast I Na. Several novel compounds, including ranolazine, GS
      458967, and F15845, appear to be the most selective inhibitors of cardiac late I
      Na reported to date. Selective inhibition of late I Na is expected to be an
      effective strategy for correcting these acquired and congenital channelopathies.

PMID- 24737239
TI  - Ubiquitylation of voltage-gated sodium channels.
AB  - Ion channel proteins are regulated by different types of posttranslational
      modifications. The focus of this review is the regulation of voltage-gated sodium
      channels (Navs) upon their ubiquitylation. The amiloride-sensitive epithelial
      sodium channel (ENaC) was the first ion channel shown to be regulated upon
      ubiquitylation. This modification results from the binding of ubiquitin ligase
      from the Nedd4 family to a protein-protein interaction domain, known as the PY
      motif, in the ENaC subunits. Many of the Navs have similar PY motifs, which have
      been demonstrated to be targets of Nedd4-dependent ubiquitylation, tagging them
      for internalization from the cell surface. The role of Nedd4-dependent regulation
      of the Nav membrane density in physiology and disease remains poorly understood.
      Two recent studies have provided evidence that Nedd4-2 is downregulated in dorsal
      root ganglion (DRG) neurons in both rat and mouse models of nerve injury-induced
      neuropathic pain. Using two different mouse models, one with a specific knockout
      of Nedd4-2 in sensory neurons and another where Nedd4-2 was overexpressed with
      the use of viral vectors, it was demonstrated that the neuropathy-linked neuronal
      hyperexcitability was the result of Nav1.7 and Nav1.8 overexpression due to Nedd4
      2 downregulation. These studies provided the first in vivo evidence of the role
      of Nedd4-2-dependent regulation of Nav channels in a disease state. This
      ubiquitylation pathway may be involved in the development of symptoms and
      diseases linked to Nav-dependent hyperexcitability, such as pain, cardiac
      arrhythmias, epilepsy, migraine, and myotonias. 

PMID- 24737240
TI  - Pharmacological insights and quirks of bacterial sodium channels.
AB  - The pedigree of voltage-gated sodium channels spans the millennia from eukaryotic
      members that initiate the action potential firing in excitable tissues to
      primordial ancestors that act as enviro-protective complexes in bacterial
      extremophiles. Eukaryotic sodium channels (eNavs) are central to electrical
      signaling throughout the cardiovascular and nervous systems in animals and are
      established clinical targets for the therapeutic management of epilepsy, cardiac
      arrhythmia, and painful syndromes as they are inhibited by local anesthetic
      compounds. Alternatively, bacterial voltage-gated sodium channels (bNavs) likely
      regulate the survival response against extreme pH conditions, electrophiles, and
      hypo-osmotic shock and may represent a founder of the voltage-gated cation
      channel family. Despite apparent differences between eNav and bNav channel
      physiology, gating, and gene structure, the discovery that bNavs are amenable to
      crystallographic study opens the door for the possibility of structure-guided
      rational design of the next generation of therapeutics that target eNavs. Here we
      summarize the gating behavior of these disparate channel members and discuss
      mechanisms of local anesthetic inhibition in light of the growing number of bNav
      structures. 

PMID- 24737241
TI  - Bacterial sodium channels: models for eukaryotic sodium and calcium channels.
AB  - Eukaryotic sodium and calcium channels are made up of four linked homologous but
      different transmembrane domains. Bacteria express sodium channels comprised of
      four identical subunits, each being analogous to a single homologous domain of
      their eukaryotic counterparts. Key elements of primary structure are conserved
      between bacterial and eukaryotic sodium and calcium channels. The simple protein
      structure of the bacterial channels has allowed extensive structure-function
      probes of key regions as well as allowing determination of several X-ray
      crystallographic structures of these channels. The structures have revealed novel
      features of sodium and calcium channel pores and elucidated the structural
      importance of many of the conserved features of primary sequence. The structural
      information has also formed the basis for computational studies probing the basis
      for sodium and calcium selectivity and gating. 

PMID- 24737238
TI  - Animal toxins influence voltage-gated sodium channel function.
AB  - Voltage-gated sodium (Nav) channels are essential contributors to neuronal
      excitability, making them the most commonly targeted ion channel family by toxins
      found in animal venoms. These molecules can be used to probe the functional
      aspects of Nav channels on a molecular level and to explore their physiological
      role in normal and diseased tissues. This chapter summarizes our existing
      knowledge of the mechanisms by which animal toxins influence Nav channels as well
      as their potential application in designing therapeutic drugs. 

PMID- 24737242
TI  - Cartilage tissue engineering using PHBV and PHBV/Bioglass scaffolds.
AB  - Scaffolds have an important role in cartilage tissue engineering.
      Poly(hydroxybutyrate-co-hydroxyvalerate) (PHBV) has been demonstrated to have
      potential as a scaffold for the three dimensional construction of engineered
      cartilage tissue. However, the poor hydrophilicity and mechanical strength
      associated with PHBV affects its clinical applications as a scaffold in cartilage
      tissue engineering. The incorporation of Bioglass (BG) into PHBV has been shown
      to improve the hydrophilicity and mechanical strength of PHBV matrices.
      Therefore, this study aimed to compare the properties of PHBV scaffolds and PHBV
      scaffolds containing 10% BG (w/w) (PHBV/10% BG) and to investigate the effects of
      these scaffolds on the properties of engineered cartilage in vivo. Rabbit
      auricular chondrocytes were seeded onto PHBV and PHBV/10% BG scaffolds.
      Differences in cartilage regeneration were compared between the neocartilage
      grown on the PHBV and the PHBV/10% BG scaffolds after 10 weeks of in vivo
      transplantation. The incorporation of BG into PHBV was observed to improve the
      hydrophilicity and compressive strength of the scaffold. Furthermore, after 10
      weeks incubation in vivo, the cartilage-like tissue formed using the PHBV/10% BG
      scaffolds was observed to be thicker, exhibit enhanced biomechanical properties
      and have a higher cartilage matrix content than that generated using the pure
      PHBV scaffolds. The results of this study demonstrate that the incorporation of
      BG into PHBV may generate composite scaffolds with improved properties for
      cartilage engineering. 

PMID- 24737243
TI  - Recent advances in biocompatible nanocarriers for delivery of chemotherapeutic
      cargoes towards cancer therapy.
AB  - Cancer is currently one of the major diseases that has gained a lot of scientific
      attention. Conventional cancer therapeutics involve surgical removal of tumors
      from patients followed by chemotherapeutic treatment. In the use of anticancer
      drugs during the chemotherapy process, patients often suffer from a variety of
      undesirable side effects including damage to normal organs. Thus, there is an
      urgent need for the development of novel strategies to overcome these side effect
      issues. Among several strategies, the utilization of nanocarriers for anticancer
      drug delivery has shown improved therapeutic efficiency of the drugs with
      minimization of the undesirable side effects. In this review, we discuss various
      types of nanocarriers recently reported in the literature for application in
      cancer therapy. We introduce some targeting ligands that have been functionalized
      on nanocarriers in order to impart specificity to the nanocarriers for targeted
      drug delivery. We also highlight some therapeutic cargoes that are commonly used
      and their therapeutic mechanisms in cancer treatment. Finally, we summarize some
      interesting stimulus strategies for controlled release of therapeutic cargoes at
      tumor sites. This review is expected to inspire new ideas and create novel
      strategies in advancing efficient cancer therapy using nanomedicine approaches. 

PMID- 24737244
TI  - Controlling enantioselectivity of esterase in asymmetric hydrolysis of aryl
      prochiral diesters by introducing aromatic interactions.
AB  - Aromatic interactions specific to aryl radicals were introduced into two
      esterases, BioH from Escherichia coli and RspE from Rhodobacter sphaeroides to
      control their enantioselectivity in the asymmetric hydrolysis of prochiral aryl
      glutaric acid diesters. As a result, the enantiomeric excess (ee) of the S
      product of dimethyl 3-phenylglutarate was increased from 25% (BioH wild type) to
      96% (B_L83F/L86F) and from 13% (RspE wild type) to >99% (R_Y27R), respectively,
      while another variant of RspE R_M121F gave a reversed ee of 50% (R-product).
      Similar enhancement or reversion of enantioselectivity were also observed in the
      hydrolysis of three other prochiral aryl diesters (dimethyl 3-(4-flouro)
      phenylglutarate, dimethyl 3-(4-cholo)-phenylglutarate and dimethyl 3-(3,4
      dicholo)-phenylglutarate). Especially, the mutant R_Y27R was shown to be an
      excellent S-selective hydrolase for prochiral aryl diesters, with ee of all S
      products >99%. In the mutants with altered enantioselectivity, the successful
      introduction of designed aromatic interactions was confirmed by molecular
      dynamics simulations and binding free energy analysis. These results demonstrate
      that aromatic interaction is one of the origins of enzyme enantioselectivity, the
      tuning of which leads to dramatic change in enantioselectivity. Besides, the
      successful engineering of the enantioselectivity in two different proteins toward
      four different substrates suggests that the introduction of aromatic interactions
      is a generally applicable strategy in the control of enantioselectivity toward
      aryl substrates.

PMID- 24737245
TI  - Smad3: an emerging target for vocal fold fibrosis.
AB  - OBJECTIVES/HYPOTHESIS: To determine the efficacy of small interfering RNA (siRNA)
      targeting Smad3 to mediate fibroplasia in vitro, to investigate the temporal
      regulation of Smad3 following vocal fold (VF) injury, and to determine the local
      and distal effects of Smad3 siRNA VF injection. STUDY DESIGN: In vitro and in
      vivo. METHODS: In vitro, Smad3 regulation was examined at both the level of
      transcription and translation in a human VF cell line in response to Smad3 siRNA
      +/- transforming growth factor beta (TGF-beta). Collagen transcription was also
      examined. In vivo, Smad3 messenger RNA (mRNA) expression was quantified as a
      function of time following rabbit VF injury. Also, the effects of injected Smad3
      siRNA were assessed at local and distal sites. RESULTS: Smad3 siRNA knocked down
      Smad3 transcription and translation and limited TGF-beta-mediated collagen mRNA
      expression with minimal cytotoxicity in vitro. In vivo, Smad3 mRNA increased 1
      day following VF injury and remained elevated through day 7. Smad3 siRNA
      injection into the uninjured vocal fold had no local or distant effect on Smad3
      mRNA at multiple organ sites. CONCLUSIONS: These data provide a foundation for
      further investigation regarding the development of novel RNA-based therapeutics
      for the VF, specifically locally delivered siRNA for challenging fibrotic
      conditions of the VF.

PMID- 24737246
TI  - ELISA analysis of urinary nephrin and podocalyxin standardized by aquaporin-2 in
      adult patients with nephrotic syndrome.
AB  - OBJECTIVE: To investigate urinary nephrin and podocalyxin standardized by
      aquaporin (AQP)-2 using the enzyme-linked immunosorbent assay (ELISA) method in
      adult nephrotic syndrome (NS) patients. METHODS: In 107 adult NS patients (27
      proliferative nephritis, 77 non-proliferative, and 3 amyloidosis) undergoing
      renal biopsy, urinary nephrin, podocalyxin and AQP2 were measured by ELISA.
      Urinary nephrin and podocalyxin were standardized by AQP2 (neph/AQP and PCX/AQP)
      and values were compared with 11 healthy controls. RESULTS: Urinary neph/AQP
      correlated positively to PCX/AQP (r = 0.51, p < 0.001). Urinary neph/AQP and
      PCX/AQP were lower in controls than NS patients. Both proliferative and non
      proliferative NS patients excreted high urinary neph/AQP and PCX/AQP without a
      significant difference between them (p > 0.05). Patients with focal segmental
      glomerular sclerosis (FSGS) excreted higher urinary neph/AQP (p = 0.09) and
      PCX/AQP (p < 0.05) compared to the other patients. Urinary neph/AQP and PCX/AQP
      were increased in the immunoglobulin M nephropathy patients. Amyloidosis patients
      excreted lower neph/AQP and PCX/AQP. The sensitivity was 0.87 and specificity
      0.37 when the neph/AQP borderline value of 0.16 was adopted [area under the curve
      (AUC) = 0.61]. The sensitivity was 0.74 and specificity 0.61 when the PCX/AQP
      borderline value was 3.06 (AUC = 0.69). CONCLUSIONS: Urinary neph/AQP and PCX/AQP
      are increased in NS patients, with FSGS patients showing the highest levels. To
      distinguish FSGS from other NS forms, the measurement of urinary PCX/AQP may be a
      practical method, and superior to neph/AQP.

PMID- 24737247
TI  - Ca2+/calmodulin potentiates I Ks in sinoatrial node cells by activating
      Ca2+/calmodulin-dependent protein kinase II.
AB  - The slow component of the delayed rectifier K(+) current (I Ks) plays an
      important role in the repolarization of action potentials in cardiac pacemaker
      cells and ventricular myocytes, and is regulated by various signaling pathways.
      Recent evidence has shown that calmodulin (CaM) is involved in modulation of
      diverse ion channels in cardiac myocytes under physiological and
      pathophysiological conditions. In the present study, we examined regulation of I
      Ks by Ca(2+)/CaM in guinea pig sinoatrial (SA) node cells using the whole-cell
      patch-clamp method. The density of I Ks was larger during intracellular dialysis
      with a higher Ca(2+) concentration (pCa 7, Ca (+)) compared to that with a low
      Ca(2+) concentration (pCa 10, Ca (-)). Intracellular application of CaM (400 nM)
      markedly potentiated I Ks with a Ca (+) pipette solution but not with a Ca (-)
      solution, thus showing that CaM potentiates I Ks in an intracellular Ca(2+)
      dependent manner. Intracellular application of a specific Ca(2+)/calmodulin
      dependent protein kinase II (CaMKII) inhibitor, autocamtide-2 inhibitory peptide
      (AIP, 500 nM), markedly reduced I Ks activity in the presence of higher
      intracellular Ca(2+). Similarly, bath application of another inhibitor, KN-93 (1
      MUM) also significantly suppressed I Ks. Finally, the stimulatory action on I Ks
      of Ca(2+)/CaM was abolished by pretreatment with KN-93. Taken together, these
      observations suggest that Ca(2+)/CaM stimulates I Ks in guinea pig SA node cells
      through activation of CaMKII. This enhancement of I Ks by CaMKII may be involved
      in modulation of SA node automaticity under physiological or pathophysiological
      condition.

PMID- 24737251
TI  - Synthesis and structures of N-alkyl-1,13-dimethoxychromeno- [2,3,4-kl]acridinium
      salts: the missing azaoxa[4]helicenium.
AB  - Helical structures are interesting due to their inherent chirality. Helicenium
      ions are triarylmethylium structures twisted into configurationally stable
      helicenes through the introduction of two heteroatom bridges between the three
      aryl substituents. Of the configurationally stable [4]helicenium ions,
      derivatives with sulfur, oxygen and nitrogen bridges have already been
      synthesised. However, one [4]helicenium ion has proven elusive, until now. We
      present herein the first synthesis of the 1,13-dimethoxychromeno[2,3,4
      kl]acridinium (DMCA(+)) [4]helicenium ion. A series of six differently N
      substituted DMCA(+) ions as their hexafluorophosphate salts are reported. Their
      cation stability was evaluated and it was found that DMCA(+) is ideally suited as
      a phase-transfer catalyst with a pKR+ of 13.0. The selectivity of nucleophilic
      addition to the central carbon atom of DMCA(+) has been demonstrated with
      diastereotopic ratios of up to 1:10. The single-crystal structures of several of
      the DMCA(+) salts were determined, and structural differences between N-aryl- and
      N-alkyl-substituted cations were observed. The results of a comparative study of
      the photophysics of the [4]helicenium ions are presented. DMCA(+) is found to be
      a potent red-emitting dye with a fluorescence quantum yield of 20 % in apolar
      solvents and a fluorescence lifetime of 12 ns. [4]Helicenium ions, including
      DMCA(+), all suffer from solvent-induced quenching, which reduces the
      fluorescence quantum yields significantly (phifl < 5 %) in polar solvents. A
      difference in photophysical properties is observed between N-aryl- and N-alkyl
      substituted DMCA(+), which has tentatively been attributed to a difference in
      molecular conformation.

PMID- 24737248
TI  - Enhanced desensitization followed by unusual resensitization in GABAA receptors
      in phospholipase C-related catalytically inactive protein-1/2 double-knockout
      mice.
AB  - Phospholipase C-related catalytically inactive proteins (PRIP-1/2) are previously
      reported to be involved in the membrane trafficking of GABAA receptor (GABAAR)
      and the regulation of intracellular Ca(2+) stores. GABAAR-mediated currents can
      be regulated by the intracellular Ca(2+). However, in PRIP-1/2 double-knockout
      (PRIP-DKO) mice, it remains unclear whether the kinetic properties of GABAARs are
      modulated by the altered regulation of intracellular Ca(2+) stores. Here, we
      investigated whether GABAAR currents (IGABA) evoked by GABA puff in layer 3 (L3)
      pyramidal cells (PCs) of the barrel cortex are altered in PRIP-DKO mice. The
      deletion of PRIP-1/2 enhanced the desensitization of IGABA but induced a hump
      like tail current (tail-I) at the GABA puff offset. IGABA and the hump-like tail
      I were suppressed by GABAAR antagonists. The enhanced desensitization of IGABA
      and the hump-like tail-I in PRIP-DKO PCs were mediated by increases in the
      intracellular Ca(2+) concentration and were largely abolished by a calcineurin
      inhibitor and ruthenium red. Calcium imaging revealed that Ca(2+)-induced Ca(2+)
      release (CICR) and subsequent store-operated Ca(2+) entry (SOCE) are more potent
      in PRIP-DKO PCs than in wild-type PCs. A mathematical model revealed that a
      slowdown of GABA-unbinding rate and an acceleration of fast desensitization rate
      by enhancing its GABA concentration dependency are involved in the generation of
      hump-like tail-Is. These results suggest that in L3 PCs of the barrel cortex in
      PRIP-DKO mice, the increased calcineurin activity due to the potentiated CICR and
      SOCE enhances the desensitization of GABAARs and slows the GABA-unbinding rate,
      resulting in their unusual resensitization following removal of GABA.

PMID- 24737252
TI  - Tanshinone IIA blocks epithelial-mesenchymal transition through HIF-1alpha
      downregulation, reversing hypoxia-induced chemotherapy resistance in breast
      cancer cell lines.
AB  - The aim of the present study was to investigate the effects of tanshinone IIA
      (Tan IIA), an active constituent of Salvia miltiorrhiza Bunge, on epithelial
      mesenchymal transition (EMT) and hypoxia-induced chemoresistance in breast cancer
      cells. To induce hypoxia, MCF-7 and HCC1973 cells were treated with 100 uM
      deferoxamine followed by doxorubicin (DOX). Cell viability and proliferation were
      examined using the CCK-8 and EdU assays, respectively. Western blot and
      immunofluorescence analyses of the expression of two EMT markers, E-cadherin and
      vimentin, were also carried out. The role of HIF-1alpha and TWIST in mediating
      the effects of Tan IIA was determined through siRNA. Based on the results,
      hypoxia-induced DOX resistance was observed in both MCF-7 and HCC1973 cells (both
      P=0.001), which was reversed with Tan IIA. Specifically, in hypoxic conditions,
      Tan IIA significantly decreased cell viability and proliferation (all P<=0.001),
      but not apoptosis. Hypoxia also significantly reduced E-cadherin and increased
      vimentin protein levels (P<=0.005), which returned to control levels with Tan
      IIA. In addition, silencing both HIF-1alpha and TWIST expression abrogated the
      effects of Tan IIA on cell viability. Taken together, Tan IIA ameliorated hypoxia
      induced DOX resistance and EMT in breast cancer cell lines, which may be
      attributed to the downregulation of HIF-1alpha expression. Further in vivo
      studies, however, are required to fully elucidate the therapeutic potential of
      Tan IIA in increasing the sensitivity of breast cancer cells to chemotherapy. 

PMID- 24737253
TI  - Vibrational and thermodynamic properties of alpha-, beta-, gamma-, and 6, 6, 12
      graphyne structures.
AB  - Electronic, vibrational, and thermodynamic properties of different graphyne
      structures, namely alpha-, beta-, gamma-, and 6, 6, 12-graphyne, are investigated
      through first principles-based quasi-harmonic approximation by using phonon
      dispersions predicted from density-functional perturbation theory. Similar to
      graphene, graphyne was shown to exhibit a structure with extraordinary electronic
      features, mechanical hardness, thermal resistance, and very high conductivity
      from different calculation methods. Hence, characterizing its phonon dispersions
      and vibrational and thermodynamic properties in a systematic way is of great
      importance for both understanding its fundamental molecular properties and also
      figuring out its phase stability issues at different temperatures. Thus, in this
      research work, thermodynamic stability of different graphyne allotropes is
      assessed by investigating vibrational properties, lattice thermal expansion
      coefficients, and Gibbs free energy. According to our results, although the
      imaginary vibrational frequencies exist for beta-graphyne, there is no such a
      negative behavior for alpha-, gamma-, and 6, 6, 12-graphyne structures. In
      general, the Gruneisen parameters and linear thermal expansion coefficients of
      these structures are calculated to be rather more negative when compared to those
      of the graphene structure. In addition, the predicted difference between the
      binding energies per atom for the structures of graphene and graphyne points out
      that graphyne networks have relatively lower phase stability in comparison with
      the graphene structures.

PMID- 24737254
TI  - Considerations on the practical application of the size-specific dose estimation
      (SSDE) method of AAPM Report 204.
AB  - Computed tomography (CT) is responsible for much of the radiation exposure to the
      population for medical purposes. The technique requires high doses that vary
      widely from center to center, and for different scanners and radiologists as
      well. In order to monitor doses to patients, the American Association of
      Physicists in Medicine has developed the size-specific dose estimate (SSDE),
      which consists of the determination of patient size dependent coefficients for
      converting the standard dosimetric index, CTDIvol, into an estimate of the dose
      actually absorbed by the patient. The present work deals with issues concerning
      the use of SSDE in the clinical practice. First the issue regarding how much SSDE
      varies when, for a given CT protocol, the scan covers slightly different volumes
      is addressed. Then, the differences among SSDE values derived from different
      patient size descriptors are investigated. For these purposes, data from a
      clinical archive are analyzed by an automatic procedure specifically developed
      for SSDE. 

PMID- 24737255
TI  - Effect of caffeine on SPECT myocardial perfusion imaging during regadenoson
      pharmacologic stress: a prospective, randomized, multicenter study.
AB  - A multicenter, double-blind, randomized study was conducted to assess the effect
      of caffeine on regadenoson stress myocardial perfusion imaging (MPI). Subjects
      with a high likelihood of coronary artery disease underwent a rest single-photon
      emission computed tomography MPI on day 1 (MPI-1) and a stress MPI with
      regadenoson on day 3 (MPI-2). Individuals with >=1 segment with a reversible
      defect received double-blind caffeine tablets (200 or 400 mg) or placebo 90 min
      before a repeat regadenoson stress MPI (MPI-3) on day 5. Overall, 207 subjects
      completed the study (caffeine 200 mg, n = 70; caffeine 400 mg, n = 71; placebo, n
      = 66). The mean number of segments with reversible defects decreased from MPI-2
      to MPI-3 in the caffeine 200 and 400 mg groups versus no significant change in
      the placebo group [mean +/- standard deviation: -0.61 +/- 1.097, -0.62 +/- 1.367,
      and 0.12 +/- 0.981, respectively (overall treatment effect, P < 0.001)]. The
      majority of subjects who received caffeine shifted to a lower ischemia size
      category from MPI-2 to MPI-3, with no clear pattern observed in subjects who
      received placebo. For caffeine exposed patients with >=3 segments with reversible
      defects at MPI-2, 21/23 had fewer detected at MPI-3. Both the 200 and 400 mg
      doses of caffeine significantly reduced the number of segments with reversible
      defects detected by regadenoson stress MPI.

PMID- 24737256
TI  - Registration and design alterations of clinical trials in critical care: a cross
      sectional observational study.
AB  - PURPOSE: In 2005 the International Committee of Medical Journal Editors issued a
      requirement that all randomized controlled trials (RCTs) be registered primarily
      to prevent selective reporting (publication bias). However, registries allow for
      alterations in study protocol. Changes occurring before (or after) study
      completion could invalidate the original study intent, leading to publication of
      misleading conclusions. In RCTs involving critically ill patients, these concerns
      may be particularly acute because mortality is high and conditions investigated
      are usually syndromes rather than specific diseases. This study was conducted to
      estimate the registration rate of RCTs in critical care; and, among registered
      RCTs, to determine timing of registration and whether sample size or primary
      outcome were altered. METHODS: We searched the MEDLINE database for RCTs that
      began after or continued through July 2005. We determined whether each trial had
      been registered and, for registered trials, compared registry data to data in the
      published manuscript. RESULTS: Approximately two-thirds (66%) of trials were
      registered. Of these, 66% of registrations occurred after enrolment had
      commenced. Overall, 6% (5/90) of trials appropriately registered a sample size
      which was unchanged from the interval between registration and publication, and
      only 12% (11/90) reported primary outcomes that were both appropriately
      registered and unchanged. CONCLUSIONS: Non-registration, or registration after
      trial initiation, are common in RCTs of critically ill patients. Among registered
      trials important protocol changes are often made between trial commencement and
      publication. This study identifies and quantifies the extent of this serious-but
      correctable-problem for RCTs in critically ill patients.

PMID- 24737257
TI  - Improving transparency in registration of randomized clinical trials in critical
      care.

PMID- 24737258
TI  - Intravenous administration of ulinastatin (human urinary trypsin inhibitor) in
      severe sepsis: a multicenter randomized controlled study.
AB  - PURPOSE: Ulinastatin, a serine protease inhibitor, inhibits several pro
      inflammatory proteases and decreases inflammatory cytokine levels and mortality
      in experimental sepsis. We studied the effect of ulinastatin on 28-day all-cause
      mortality in a double-blind trial in patients with severe sepsis in seven Indian
      hospitals. METHODS: Patients with sepsis were randomized within 48 h of onset of
      one or more organ failures to receive intravenous administration of ulinastatin
      (200,000 IU) or placebo 12 hourly for 5 days. RESULTS: Of 122 randomized
      subjects, 114 completed the study (55 receiving ulinastatin, 59 receiving
      placebo). At baseline, the mean APACHE II score was 13.4 (SD = 4.4), 48 (42 %)
      patients were receiving mechanical ventilation, 58 (51 %) were on vasopressors,
      and 35 % had multiple organ failure. In the modified intention-to-treat analysis
      (patients receiving six or more doses of study drugs), 28-day all-cause mortality
      was 7.3 % with ulinastatin (4 deaths) versus 20.3 % (12 deaths) with placebo (p =
      0.045). On multivariate analysis too, treatment with ulinastatin (odds ratio
      0.26, 95 % CI 0.07-0.95; p = 0.042) independently decreased 28-day all-cause
      mortality. However, the mortality difference did not reach statistical
      significance in the intention-to-treat analysis [10.2 % (6/59 deaths) with
      ulinastatin versus 20.6 % (13/63 deaths) in the placebo group; p = 0.11]. The
      ulinastatin group had lower incidence of new-onset organ failure (10 vs. 26
      patients, p = 0.003), more ventilator-free days (mean +/- SD 19.4 +/- 10.6 days
      vs. 10.2 +/- 12.5 days, p = 0.019), and shorter hospital stay (11.8 +/- 7.1 days
      vs. 24.2 +/- 7.2 days, p < 0.001). CONCLUSIONS: In this pilot study, intravenous
      administration of ulinastatin reduced mortality in patients with severe sepsis in
      the modified intention-to-treat analysis, but not in the intention-to-treat
      analysis.

PMID- 24737259
TI  - Paradoxical massive pulmonary embolism with a straddling thrombus across a patent
      foramen ovale.

PMID- 24737260
TI  - Respiratory variations in the arterial pressure during mechanical ventilation
      reflect volume status and fluid responsiveness.
AB  - Optimal fluid management is one of the main challenges in the care of the
      critically ill. However, the physiological parameters that are commonly monitored
      and used to guide fluid management are often inadequate and even misleading. From
      1987 to 1989 we published four experimental studies which described a method for
      predicting the response of the cardiac output to fluid administration during
      mechanical ventilation. The method is based on the analysis of the variations in
      the arterial pressure in response to a mechanical breath, which serves as a
      repetitive hemodynamic challenge. Our studies showed that the systolic pressure
      variation and its components are able to reflect even small changes in the
      circulating blood volume. Moreover, these dynamic parameters provide information
      about the slope of the left ventricular function curve, and therefore predict the
      response to fluid administration better than static preload parameters. Many new
      dynamic parameters have been introduced since then, including the pulse pressure
      (PPV) and stroke volume (SVV) variations, and various echocardiographic and other
      parameters. Though seemingly different, all these parameters are based on
      measuring the response to a predefined preload-modifying maneuver. The clinical
      usefulness of these 'dynamic' parameters is limited by many confounding factors,
      the recognition of which is absolutely necessary for their proper use. With more
      than 20 years of hindsight we believe that our early studies helped pave the way
      for the recognition that fluid administration should ideally be preceded by the
      assessment of "fluid responsiveness". The introduction of dynamic parameters into
      clinical practice can therefore be viewed as a significant step towards a more
      rational approach to fluid management.

PMID- 24737261
TI  - Angioedema induced by angiotensin converting enzyme inhibitors, potentiated by m
      TOR inhibitors: successful treatment with icatibant.

PMID- 24737262
TI  - Should we use anticoagulant lock for short-term haemodialysis catheter in the
      ICU?

PMID- 24737263
TI  - Understanding paracetamol-induced liver failure.

PMID- 24737266
TI  - Why a career in psychiatry?
AB  - OBJECTIVES: To reflect upon the factors that might motivate one to undertake a
      career in psychiatry from the personal perspective of a current registrar in
      training. CONCLUSIONS: The reasons for choosing a career path in psychiatry are
      complex, and relate to an individual doctor's life experience, training
      experiences and own value system. Dissatisfaction with the traditional "medical
      model" of illness may be a contributing factor, with a perception that psychiatry
      may embrace the biopsychosocial model of illness more fully. Beyond this, a
      particular interest in the poetry inherent to an individual's story and
      appreciation of the artistic underpinnings of medicine may also contribute.

PMID- 24737265
TI  - Standardizing vitamin D assays: the way forward.
AB  - For a number of years it has been widely assumed that measurement of serum 25
      hydroxyvitamin D [25(OH)D] concentration is the best approach to assessing an
      individual's vitamin D status. However, it has also been recognized that there is
      substantial within-assay variation in 25(OH)D measurement and even greater
      between-assay variability. Such assay variation clearly confounds attempts to
      define what constitutes the diagnosis of hypovitaminosis D. Importantly, assay
      variability makes pooling of 25(OH)D results from different studies in systematic
      reviews for the specific purpose of determining dose-response and/or clinical cut
      points at best problematic. Therefore, to develop and implement evidence-based
      clinical guidelines, it is essential that 25(OH)D measurement be standardized in
      both clinical and research laboratories. In this Perspective we outline a way
      forward toward achieving this goal-the Vitamin D Standardization Program (VDSP).

PMID- 24737267
TI  - Functional assessment of the mouse heart by MRI with a 1-min acquisition.
AB  - In vivo assessment of heart function in mice is important for basic and
      translational research in cardiology. MRI is an accurate tool for the
      investigation of the anatomy and function in the preclinical setting; however,
      the long scan duration limits its usage. We aimed to reduce the acquisition time
      of cine MRI to 1 min. We employed spatiotemporal compressed sensing and parallel
      imaging to accelerate retrospectively gated cine MRI. We compared the functional
      parameters derived from full and undersampled data in Cartesian and radial MRI by
      means of Bland-Altman plots. We found that the scan time for the whole heart
      could be reduced to 2 min with Cartesian sampling and to 1 min with radial
      sampling. Despite a reduction in the signal-to-noise ratio, the accuracy in the
      estimation of left and right ventricular volumes was preserved for all tested
      subjects. This method can be used to perform accurate functional MRI examinations
      in mice for high-throughput phenotyping or translational studies.

PMID- 24737268
TI  - Absence of circumflex artery with superdominant right coronary: a classic
      anatomical dissection study.
AB  - PURPOSE: We report a very unusual case of variant coronary artery anatomy,
      discovered during anatomical dissection in a medical school. METHODS: The heart
      from a very advanced age donor was dissected using classic anatomical techniques
      RESULTS: The right coronary artery showed a superdominant pattern, extending
      beyond the crux of the heart and circling the atrioventricular groove almost
      completely. It followed the usual path of the absent circumflex artery, and ended
      as a slender branch which almost reached the origin of the anterior
      interventricular artery. CONCLUSIONS: To our knowledge, these are the first
      reported dissection images of this kind of coronary artery variation. It may have
      clinical consequences, either leading to more accelerated atherosclerotic changes
      or causing technical difficulties during cardiac surgery.

PMID- 24737269
TI  - Variation of DNA damage levels in peripheral blood mononuclear cells isolated in
      different laboratories.
AB  - This study investigated the levels of DNA strand breaks and formamidopyrimidine
      DNA glycosylase (FPG) sensitive sites, as assessed by the comet assay, in
      peripheral blood mononuclear cells (PBMC) from healthy women from five different
      countries in Europe. The laboratory in each country (referred to as 'centre')
      collected and cryopreserved PBMC samples from three donors, using a standardised
      cell isolation protocol. The samples were analysed in 13 different laboratories
      for DNA damage, which is measured by the comet assay. The study aim was to assess
      variation in DNA damage in PBMC samples that were collected in the same way and
      processed using the same blood isolation procedure. The inter-laboratory
      variation was the prominent contributor to the overall variation. The inter
      laboratory coefficient of variation decreased for both DNA strand breaks (from 68
      to 26%) and FPG sensitive sites (from 57 to 12%) by standardisation of the
      primary comet assay endpoint with calibration curve samples. The level of DNA
      strand breaks in the samples from two of the centres (0.56-0.61 lesions/10(6) bp)
      was significantly higher compared with the other three centres (0.41-0.45
      lesions/10(6) bp). In contrast, there was no difference between the levels of FPG
      sensitive sites in PBMC samples from healthy donors in the different centres
      (0.41-0.52 lesion/10(6) bp). 

PMID- 24737270
TI  - Summaries for patients. Treatment trials to determine whether statins are the
      cause of a patient's discomfort.

PMID- 24737271
TI  - Chronic hepatitis C virus infection in the United States, National Health and
      Nutrition Examination Survey 2003 to 2010.
AB  - BACKGROUND: Knowledge of the number of persons with chronic hepatitis C virus
      (HCV) infection in the United States is critical for public health and policy
      planning. OBJECTIVE: To estimate the prevalence of chronic HCV infection between
      2003 and 2010 and to identify factors associated with this condition. DESIGN:
      Nationally representative household survey. SETTING: U.S. noninstitutionalized
      civilian population. PARTICIPANTS: 30,074 NHANES (National Health and Nutrition
      Examination Survey) participants between 2003 and 2010. MEASUREMENTS: Interviews
      to ascertain demographic characteristics and possible risks and exposures for HCV
      infection. Serum samples from participants aged 6 years or older were tested for
      antibody to HCV; if results were positive or indeterminate, the samples were
      tested for HCV RNA, which indicates current chronic infection. RESULTS: Based on
      273 participants who tested positive for HCV RNA, the estimated prevalence of HCV
      infection was 1.0% (95% CI, 0.8% to 1.2%), corresponding to 2.7 million
      chronically infected persons (CI, 2.2 to 3.2 million persons) in the U.S.
      noninstitutionalized civilian population. Infected persons were more likely to be
      aged 40 to 59 years, male, and non-Hispanic black and to have less education and
      lower family income. Factors significantly associated with chronic HCV infection
      were illicit drug use (including injection drugs) and receipt of a blood
      transfusion before 1992; 49% of persons with HCV infection did not report either
      risk factor. LIMITATION: Incarcerated and homeless persons were not surveyed.
      CONCLUSION: This analysis estimated that approximately 2.7 million U.S. residents
      in the population sampled by NHANES have chronic HCV infection, about 500,000
      fewer than estimated in a similar analysis between 1999 and 2002. These data
      underscore the urgency of identifying the millions of persons who remain infected
      and linking them to appropriate care and treatment. PRIMARY FUNDING SOURCE: None.

PMID- 24737272
TI  - N-of-1 (single-patient) trials for statin-related myalgia.
AB  - BACKGROUND: Statin-related myalgia is difficult to distinguish from other
      conditions causing myalgia and may often lead to statin discontinuation.
      OBJECTIVE: To compare the effect of statin rechallenge with placebo in patients
      with prior statin-related myalgia and to determine whether patients resumed
      statin therapy after evaluating the results. DESIGN: N-of-1 trial with 3 double
      blind, crossover comparisons separated by 3-week washout periods.
      (Clinicaltrials.gov: NCT01259791) SETTING: Tertiary care lipid clinic. PATIENTS:
      Patients with prior statin-related myalgia with or without mild elevation of
      creatine kinase levels. INTERVENTION: Rechallenge with the statin that was
      previously associated with myalgia within 3 weeks of open-label use versus
      matching placebo. MEASUREMENTS: Weekly visual analogue scale (VAS) scores for
      myalgia and specific symptoms (VAS myalgia score and symptom-specific VAS score,
      respectively), pain interference scores, and pain severity scores were recorded
      during the 3-week periods when patients were receiving placebo or statin. The
      primary outcome was the VAS myalgia score (range, 0 to 100 mm). RESULTS: Eight
      patients (mean age, 66 years [SD, 8 years]; 88% women, all with high 10-year
      Framingham cardiovascular risk) participated in n-of-1 trials. Seven patients
      completed 3 treatment pairs, and 1 completed 2 treatment pairs. For each n-of-1
      trial, no statistically significant differences were seen between statin and
      placebo in the VAS myalgia score, symptom-specific VAS score, pain interference
      score, and pain severity score. Five patients resumed open-label statin
      treatment, with a median posttrial follow-up of 10 months. LIMITATION: Results
      are limited by the small sample size and cannot be extended to patients with
      longer onset of myalgia after statin initiation. CONCLUSION: In selected patients
      with a history of statin-related myalgia whose symptoms are difficult to
      evaluate, n-of-1 trials may be a useful method for determining statin
      tolerability. PRIMARY FUNDING SOURCE: Western University, London, Ontario,
      Canada.

PMID- 24737273
TI  - Gender differences in time spent on parenting and domestic responsibilities by
      high-achieving young physician-researchers.
AB  - BACKGROUND: Female physician-researchers do not achieve career success at the
      same rate as men. Differences in nonprofessional responsibilities may partially
      explain this gap. OBJECTIVE: To investigate the division of domestic labor by
      gender in a motivated group of early-career physician-researchers. DESIGN:
      Nationwide postal survey between 2010 and 2011. SETTING: United States.
      PARTICIPANTS: Physician recipients of National Institutes of Health K08 or K23
      awards between 2006 and 2009 with active academic affiliation at the time of the
      survey. MEASUREMENTS: Time spent on parenting and domestic tasks was determined
      through self-report. Among married or partnered respondents with children, a
      linear regression model of time spent on domestic activities was constructed
      considering age, gender, race, specialty, MD or MD/PhD status, age of youngest
      child, number of children, work hours, K award type, and spousal employment.
      RESULTS: A 74% response rate was achieved, and 1049 respondents were academic
      physicians. Women were more likely than men to have spouses or domestic partners
      who were employed full-time (85.6% [95% CI, 82.7% to 89.2%] vs. 44.9% [CI, 40.8%
      to 49.8%]). Among married or partnered respondents with children, after
      adjustment for work hours, spousal employment, and other factors, women spent 8.5
      more hours per week on domestic activities. In the subgroup with spouses or
      domestic partners who were employed full-time, women were more likely to take
      time off during disruptions of usual child care arrangements than men (42.6% [CI,
      36.6% to 49.0%] vs. 12.4% [CI, 5.4% to 19.5%]). LIMITATIONS: Analyses relied on
      self-reported data. The study design did not enable investigation of the
      relationship between domestic activities and professional success. CONCLUSION: In
      this sample of career-oriented professionals, gender differences in domestic
      activities existed among those with children. Most men's spouses or domestic
      partners were not employed full-time, which contrasted sharply with the
      experiences of women. PRIMARY FUNDING SOURCE: National Institutes of Health.

PMID- 24737274
TI  - A woman physician-researcher's work is never done.

PMID- 24737275
TI  - Management of obstructive sleep apnea in adults.

PMID- 24737276
TI  - In the clinic. Asthma.

PMID- 24737277
TI  - A comparative study of PKH67, DiI, and BrdU labeling techniques for tracing rat
      mesenchymal stem cells.
AB  - Mesenchymal stem cells (MSCs) have generated a great deal of promise as a
      potential source of cells for cell-based therapies. Various labeling techniques
      have been developed to trace MSC survival, migration, and behavior in vitro or in
      vivo. In the present study, we labeled MSCs derived from rat bone marrow (rMSCs)
      with florescent membrane dyes PKH67 and DiI, and with nuclear labeling using 5
      MUM BrdU and 10 MUM BrdU. The cells were then cultured for 6 d or passaged (1-3
      passages). The viability of rMSCs, efficacy of fluorescent expression, and
      transfer of the dyes were assessed. Intense fluorescence in rMSCs was found
      immediately after membrane labeling (99.3 +/- 1.6% PKH67+ and 98.4 +/- 1.7% DiI+)
      or after 2 d when tracing of nuclei was applied (91.2 +/- 4.6% 10 MUM BrdU+ and
      77.6 +/- 4.6% 5 MUM BrdU+), which remained high for 6 d. Viability of labeled
      cells was 91 +/- 3.8% PKH67+, 90 +/- 1.5% DiI+, 91 +/- 0.8% 5 MUM BrdU+, and 76.9
      +/- 0.9% 10 MUM BrdU+. The number of labeled rMSCs gradually decreased during the
      passages, with almost no BrdU+ nuclei left at final passage 3. Direct cocultures
      of labeled rMSCs (PKH67+ or DiI+) with unlabeled rMSCs revealed almost no dye
      transfer from donor to unlabeled recipient cells. Our results confirm that
      labeling of rMSCs with PKH67 or DiI represents a non-toxic, highly stable, and
      efficient method suitable for steady tracing of cells, while BrdU tracing is more
      appropriate for temporary labeling due to decreasing signal over time. 

PMID- 24737278
TI  - Comparison of some antioxidant properties of plant extracts from Origanum
      vulgare, Salvia officinalis, Eleutherococcus senticosus and Stevia rebaudiana.
AB  - Phenolic compounds from plants are known for their antioxidant properties and
      have been proposed as therapeutic agents to counteract oxidative stress. However,
      under normal circumstances, the body only receives a very small amount of these
      substances in the diet. We have investigated the effect of extracts from known
      and frequently used plants as part of diet, food seasoning, medicinal tea, and
      sweetener at different concentrations on the ability to scavenge free radicals,
      to affect antioxidant enzymes, and finally in the survival of cancer cell lines.
      We found extract concentrations of about 100 MUg.ml(-1) more indicative in the
      assessment of all parameters investigated. Ginseng possessed a very good ability
      to scavenge superoxide and hydroxyl radicals, while stevia also manifested
      significant effects against hydroxyl radicals. Both extracts also showed NO
      decomposition ability. The antioxidant defense system against the excessive
      production of radicals in mitochondria was sufficient. In contrast, the range of
      operating concentrations for sage and oregano mainly presented no significant
      effects against reactive oxygen and nitrogen species. Taken together with the
      significantly reduced activity of glutathione peroxidase, this led to the
      depletion of glutathione. The demonstrated modulation of redox state capability
      was sufficient to affect the viability of all tested cancer cell lines, but
      especially A-549, CEM and HeLa by oregano extract. Results support the promising
      role of the tested extracts as a source of compounds for further in vivo studies
      with the ability to powerfully interfere with or modify the redox state of cells
      according to the type of disease, which is expected to be associated with
      oxidative stress. 

PMID- 24737279
TI  - A qualitative exploration of fishing and fish consumption in the Gullah/Geechee
      culture.
AB  - The Gullah/Geechee (G/G) heritage is rooted in a culture largely dependent on
      fish and seafood as a primary food source. Research suggests that African
      American (AA) fishers in the Southeastern US consume larger amounts of fish,
      potentially exposing them to higher environmental contaminant levels. This in
      depth study was conducted to explore G/G and AA Sea Island attitudes,
      perceptions, and cultural beliefs about fishing in one urban and two rural South
      Carolina coastal counties. Results indicated that study participants in rural
      counties had slightly different perspectives of fishing (e.g. fishing as an
      essential dietary supplement) than in urban counties where fishing was viewed
      more as relaxation. Major misperceptions existed in all counties between fish
      consumption advisories related to pollution versus harvesting restrictions
      associated with fishing regulations. Providing clear, culturally tailored health
      messages regarding fish advisories will promote more informed choices about fish
      consumption that will minimize potential exposures to environmental pollutants. 

PMID- 24737280
TI  - Self-recovering tough gel electrolyte with adjustable supercapacitor performance.

PMID- 24737281
TI  - Evaluation of developmental toxicity using undifferentiated human embryonic stem
      cells.
AB  - An embryonic stem cell test (EST) has been developed to evaluate the embryotoxic
      potential of chemicals with an in vitro system. In the present study, novel
      methods to screen toxic chemicals during the developmental process were evaluated
      using undifferentiated human embryonic stem (hES) cells. By using surface marker
      antigens (SSEA-4, TRA-1-60 and TRA-1-81), we confirmed undifferentiated
      conditions of the used hES cells by immunocytochemistry. We assessed the
      developmental toxicity of embryotoxic chemicals, 5-fluorouracil, indomethacin and
      non-embryotoxic penicillin G in different concentrations for up to 7 days. While
      expressions of the surface markers were not significantly affected, the
      embryotoxic chemicals influenced their response to pluripotent ES cell markers,
      such as OCT-4, NANOG, endothelin receptor type B (EDNRB), secreted frizzled
      related protein 2 (SFRP2), teratocarcinoma-derived growth factor 1 (TDGF1), and
      phosphatase and tensin homolog (PTEN). Most of the pluripotent ES cell markers
      were down-regulated in a dose-dependent manner after treatment with embryotoxic
      chemicals. After treatment with 5-fluorouracil, indomethacin and penicillin G, we
      observed a remarkable convergence in the degree of up-regulation of development,
      cell cycle and apoptosis-related genes by gene expression profiles using an
      Affymetrix GeneChips. Taken together, these results suggest that embryotoxic
      chemicals have cytotoxic effects, and modulate the expression of ES cell markers
      as well as development-, cell cycle- and apoptosis-related genes that have
      pivotal roles in undifferentiated hES cells. Therefore, we suggest that hES cells
      may be useful for testing the toxic effects of chemicals that could impact the
      embryonic developmental stage.

PMID- 24737282
TI  - Abstracts from the Society of Academic and Research Surgery (SARS) Annual
      Meeting, 8-9 January 2014, Cambridge, England.

PMID- 24737283
TI  - Unmet need in Behcet's disease: most patients in routine follow-up continue to
      have oral ulcers.
AB  - The clinical course of Behcet's disease (BD) as a multisystemic disorder with a
      remitting-relapsing nature is insufficiently explored. As complete remission
      should be aimed in all inflammatory diseases, we investigated the frequency of
      complete remission in patients with BD followed in long-term, routine practice.
      In this retrospective study, 258 patients with BD who were regularly followed in
      outpatient clinics were assessed. The demographic and clinical data for active
      organ manifestations and treatment protocols were evaluated, and "complete
      remission" for this study was defined as no sign of any disease manifestation in
      the current visit and the preceding month. Two hundred fifty-eight patients with
      BD (F/M 130/128, mean age 41.1 +/- 11.5 years) were included to the study.
      Mucocutaneous disease was present in 48.4 % (n = 125). Mean visit number was 6.8
      +/- 2.7, and mean follow-up duration was 45.8 +/- 36.5 months. Patients were
      clinically active in 67.2 % (n = 1,182) of the total visits (n = 1,757), which
      increased to 75.6 % (68.1-90.3) when the month preceding the visit was also
      included. The most common active manifestation was oral ulcers (39.4-63.2 %)
      followed by other mucocutaneous manifestations and musculoskeletal involvement.
      When multivariate analysis was performed, oral ulcers, which are the main cause
      of the clinical activity, negatively correlated with immunosuppressive treatments
      (beta = -0.356, p < 0.000) and age (beta = -0.183, p = 0.04). It is fairly
      difficult to achieve complete remission in BD with current therapeutic regimens.
      The reluctance of the clinician to be aggressive for some BD manifestations with
      low morbidity, such as mucocutaneous lesions and arthritis, might be influencing
      the continuous, low-disease activity state, especially due to oral ulcers, in BD
      patients.

PMID- 24737284
TI  - Cutaneous manifestations of adult-onset Still's disease: a case report and review
      of literature.
AB  - Adult onset Still's disease (AOSD) is a systemic inflammatory disorder of unknown
      etiology and pathogenesis characterized by high spiking fever, arthralgia or
      arthritis, sore throat, lymphadenopathy, hepatosplenomegaly, serositis, and
      transient cutaneous manifestations. Although more common in children, cases are
      seen also in adults. Cutaneous involvement is common and may be suggestive for
      the diagnosis. A case of AOSD in a 35-year-old man is reported here, presenting
      with urticarial maculopapular rash of trunk, high spiking fever, acute
      respiratory distress syndrome, and myopericarditis. Skin biopsy showed
      interstitial and perivascular mature CD15(+) neutrophils. A comprehensive review
      of literature showed that cutaneous involvement occurs in about 80 % of patients,
      with various clinical presentations. The most common skin manifestation is an
      evanescent salmon pink or erythematous maculopapular exanthema, predominantly on
      the trunk and proximal limbs, with rare involvement of face and distal limbs.
      Less common manifestations include persistent erythematous plaques and pustular
      lesions. A constant histopathologic finding is the presence of interstitial
      dermal neutrophils aligned between the collagen bundles. This pattern may provide
      an easy accessible clue for the definitive diagnosis of AOSD and exclude other
      diagnosis such as drug eruptions or infectious diseases. 

PMID- 24737285
TI  - Increased circulating T-helper 22 cells in patients with dilated cardiomyopathy.
AB  - Recently, the newly determined interleukin (IL)-22-producing T-helper (Th) 22
      cell has been implicated to be involved in the pathogenesis of autoimmune
      diseases. However, its role in the pathogenesis of dilated cardiomyopathy (DCM)
      has yet to be elucidated. A total of 30 patients with DCM and 30 healthy controls
      were enrolled in the present study. The levels of Th22, Th17 and Th1 cells in the
      peripheral blood were analyzed by flow cytometry. Levels of plasma IL-22 and
      autoantibody adenine nucleotide translocator (ANT) were assessed using the ELISA.
      The key transcription factor of Th22, aryl hydrocarbon receptor (AHR), was
      assessed using quantitative polymerase chain reaction. Additionally, clinical
      data on the brain natriuretic peptide (BNP), C-reactive protein (CRP) and
      erythrocyte sedimentation rate (ESR) were collected. In comparison with those in
      the control group, significantly elevated levels of Th22, Th17 and Th1 cells were
      detected in patients with DCM (all P<0.01). Similarly, elevated mRNA levels of
      peripheral AHR were detected in patients with DCM. The percentage of Th22 cells
      was higher in ANT-positive compared with ANT-negative patients with DCM. The
      levels of BNP and CRP, but not ESR, showed a significant positive correlation
      with those of Th22 cells. With regard to the concentrations of plasma IL-22, no
      statistical difference was found between patients with DCM and the healthy
      controls, nor did it demonstrate a statistical correlation with the percentage of
      Th22 cells. In conclusion, the present study showed that patients with DCM,
      particularly those of the ANT autoantibody positive subjects, exhibit elevated
      levels of peripheral Th22 cells, indicating that a Th22 immune response may be
      implicated in the pathogenesis of DCM. 

PMID- 24737287
TI  - Interview with Thierry Ponchon, Editor-in-Chief of Endoscopy International Open.

PMID- 24737286
TI  - Video-based method of quantifying performance and instrument motion during
      simulated phonosurgery.
AB  - OBJECTIVES/HYPOTHESIS: To investigate the use of the Video-Based
      Phonomicrosurgery Instrument Tracking System to collect instrument position data
      during simulated phonomicrosurgery and calculate motion metrics using these data.
      We used this system to determine if novice subject motion metrics improved over 1
      week of training. STUDY DESIGN: Prospective cohort study. METHODS: Ten subjects
      performed simulated surgical tasks once per day for 5 days. Instrument position
      data were collected and used to compute motion metrics (path length, depth
      perception, and motion smoothness). Data were analyzed to determine if motion
      metrics improved with practice time. Task outcome was also determined each day,
      and relationships between task outcome and motion metrics were used to evaluate
      the validity of motion metrics as indicators of surgical performance. RESULTS:
      Significant decreases over time were observed for path length (P < .001), depth
      perception (P < .001), and task outcome (P < .001). No significant change was
      observed for motion smoothness. Significant relationships were observed between
      task outcome and path length (P < .001), depth perception (P < .001), and motion
      smoothness (P < .001). CONCLUSIONS: Our system can estimate instrument trajectory
      and provide quantitative descriptions of surgical performance. It may be useful
      for evaluating phonomicrosurgery performance. Path length and depth perception
      may be particularly useful indicators.

PMID- 24737289
TI  - Selenium-binding protein 1 is associated with the degree of colorectal cancer
      differentiation and is regulated by histone modification.
AB  - The aim of the present study was to examine the regulation of selenium binding
      protein 1 (SELENBP1) expression in colorectal cancer (CRC). Samples of cancer
      tissue and adjacent normal mucosa were collected from 83 CRC patients, and
      analyzed for SELENBP1 expression by 2D-DIGE, immunoblotting, RT-PCR and
      immunostaining. Expression levels of SELENBP1, carcinoembryonic antigen (CEA) and
      alkaline phosphatase (AKP) were determined in cultures of human colon cancer cell
      lines (SW480, SW620 and HT29) folllowing treatment with i) sodium butyrate (NaB,
      2 mM), a differentiation inducer; ii) Trichostatin A (TSA, 0.3 uM), a histone
      deacetylase inhibitor; or iii) 5'-aza-2'-deoxycytidine (5-Aza-dC, 5 uM), a DNA
      methylation inhibitor. SELENBP1 expression was found to be downregulated (2.54
      fold) in the CRC samples as determined by 2D-DIGE and confirmed by immunoblotting
      and RT-PCR. SELENBP1 expression was correlated with the degree of
      differentiation, but not with TNM stage or lymph node metastasis, and was higher
      in benign polyps (1.97+/-0.57) than in CRC tissues (0.96+/-0.59). In the CRC cell
      lines, NaB treatment led to the upregulation of SELENBP1, CEA and AKP when
      compared with the untreated cells (2.24- to 4.82-fold). SELENBP1 was also
      upregulated in cells treated with TSA alone (1.25- to 3.64-fold), or in
      combination with 5-Aza-dC (1.32- to 4.13-fold). In CRC, the downregulated
      SELENBP1 expression was reactivated by inducing differentiation. Therefore,
      SELENBP1 is a potential pharmacological target for individualized CRC treatment. 

PMID- 24737290
TI  - Quality of life and behavioral functioning in Dutch pediatric patients with
      hereditary spherocytosis.
AB  - The objective of this study was to evaluate health-related quality of life
      (HRQoL) and behavioral functioning in pediatric patients with hereditary
      spherocytosis (HS). A cross-sectional study was conducted in 132 Dutch children
      and adolescents with HS and aged 8-18 years of whom 48 underwent splenectomy
      prior to the study. HRQoL was assessed using the KIDSCREEN-27, and behavioral
      functioning was evaluated using the strength and difficulties questionnaire
      (SDQ). Scores of pediatric patients with HS were compared to a Dutch norm
      population. Additionally, the effects of three factors were assessed: fatigue,
      self-image, and parents' perceived vulnerability (measured with the checklist
      individual strength, the self-perception profile for children and adolescents,
      and the child vulnerability scale). Both unsplenectomised and splenectomised
      pediatric patients reported lower HRQoL on the domain physical well-being
      (KIDSCREEN-27) compared to Dutch peers. For behavioral functioning, parents of
      both groups reported more emotional problems (SDQ) compared to the norm
      population. Pediatric patients with lower scores on physical well-being
      experienced more fatigue. The patients' perceived social acceptance and parents'
      perceived vulnerability appeared as determinants of emotional problems.
      CONCLUSION: Pediatric patients in the current study generally report few
      complaints, and the results suggest that these patients overall have a strong
      ability to cope with HS. Despite these few complaints, fatigue and parents'
      perceived vulnerability seem to be important determinants for lower HRQoL and
      more emotional problems. Therefore, screening on these factors could serve as an
      addition to the treatment of HS, to help pediatric patients who are at risk for
      lower HRQoL or more emotional problems.

PMID- 24737291
TI  - A study on clinical and radiological features and outcome in patients with
      posterior reversible encephalopathy syndrome (PRES).
AB  - Posterior reversible encephalopathy syndrome (PRES) is characterized clinically
      by headaches, seizures, vomiting, nausea, visual abnormalities, and altered
      mental function and is often (but not invariably) accompanied by parieto
      occipital imaging features. The aim of this study is to describe the clinical and
      radiological features and outcome following PRES in a paediatric cohort. From a
      retrospectively identified cohort, case records were studied to confirm a
      diagnosis of PRES. Neuroimaging was reviewed again to assign to recently
      described radiological subtypes parieto-occipital pattern, holohemispheric
      watershed pattern, dominant superior frontal sulcus pattern, and asymmetrical or
      partial expression of the three primary patterns (A/P). Patient outcome was
      measured by the modified Rankin scale (mRS) scores. Nine boys and three girls
      with mean age of 12 were identified. Hypertensive episodes (n = 11), tacrolimus
      toxicity (n = 4), and autoimmunity (n = 1) were identified as potential risk
      factors/etiologies. Their median mRS at the peak of illness was 2 (range 2-5);
      three children required intensive care support. After mean follow-up of 35 months
      (median 37 months; range 3-60 months), all patients improved significantly with
      mean mRS of 1 (median 1; range 0-1). CONCLUSION: PRES is easily recognizable by
      the clinical and radiological features. Although severe at presentation, the
      outcome from this condition is favorable.

PMID- 24737292
TI  - Hypermethylation of the enolase gene (ENO2) in autism.
AB  - It has been hypothesized that dysregulation of brain-expressed genes is the major
      predisposing underlying mechanism for autism. This dysregulation may be mediated
      by differential methylation of CpG sites within gene promoters, which could be
      candidate biomarkers and used for early clinical screening of autism. A total of
      131 pairs of age- and sex-matched autistic and control subjects were recruited in
      this study. Peripheral blood cells were analyzed. The first five pairs were
      randomly applied to array-based genome-wide methylation studies. A neuron
      specific gene, ENO2, was found to be hypermethylated in the autistic samples.
      This difference was validated by bisulfite sequencing PCR (BSP). The differential
      expression of ENO2 gene was further analyzed with RT-qPCR and ELISA. The
      hypermethylation of ENO2 within the promoter region was confirmed by BSP to be
      present in 14.5 % (19/131) of the total of the autistic samples. The mean ENO2
      RNA level in these 19 autistic samples was reduced by about 70 % relative to that
      in controls. The average level of ENO2 protein expression in the 19 autistic
      samples (15.18 +/- 3.51 MUg/l) was about half of that in the controls (33.86 +/-
      8.16 MUg/l). CONCLUSION: These findings suggest that reduced ENO2 expression may
      be a biomarker for a subset of autistic children.

PMID- 24737293
TI  - Novel adenosine deaminase 2 mutations in a child with a fatal vasculopathy.
AB  - Adenosine deaminase 2 (ADA2) deficiency due to CECR1 mutations is a recently
      defined disorder that involves systemic inflammation and vasculopathy often
      associated with polyarteritis nodosa. We report on a 5-year-old girl with a
      severe vasculopathy who carried two novel mutations in CECR1. CONCLUSION:
      Identification of CECR1 mutations in patients with vasculopathy may lead to
      earlier diagnosis of ADA2 deficiency.

PMID- 24737294
TI  - Synthesis, pi-face-selective aggregation, and pi-face chiral recognition of
      configurationally stable C(3)-symmetric propeller-chiral molecules with a pi
      core.
AB  - The C3 -symmetric propeller-chiral compounds (P,P,P)-1 and (M,M,M)-1 with planar
      pi-cores perpendicular to the C3 -axis were synthesized in optically pure states.
      (P,P,P)-1 possesses two distinguishable propeller-chiral pi-faces with rims of
      different heights named the (P/L)-face and (P/H)-face. Each face is
      configurationally stable because of the rigid structure of the helicenes
      contained in the pi-core. (P,P,P)-1 formed dimeric aggregates in organic
      solutions as indicated by the results of (1) H NMR, CD, and UV/Vis spectroscopy
      and vapor pressure osmometry analyses. The (P/L)/(P/L) interactions were observed
      in the solid state by single-crystal X-ray analysis, and they were also
      predominant over the (P/H)/(P/H) and (P/L)/(P/H) interactions in solution, as
      indicated by the results of (1) H and 2D NMR spectroscopy analyses. The
      dimerization constant was obtained for a racemic mixture, which showed that the
      heterochiral (P,P,P)-1/(M,M,M)-1 interactions were much weaker than the
      homochiral (P,P,P)-1/(P,P,P)-1 interactions. The results indicated that the
      propeller-chiral (P/L)-face interacts with the (P/L)-face more strongly than with
      the (P/H)-face, (M/L)-face, and (M/H)-face. The study showed the pi-face
      selective aggregation and pi-face chiral recognition of the configurationally
      stable propeller-chiral molecules.

PMID- 24737296
TI  - Newly derived GH43 gene from compost metagenome showing dual xylanase and
      cellulase activities.
AB  - A metagenomic fosmid library was constructed from compost microbial communities
      that were collected from various farms throughout the Khon Kaen province,
      Thailand. The library was enriched in carboxymethylcellulose (CM-cellulose)-
      containing media prior to the screening of clones capable of degrading cellulosic
      materials. Two clones were selected for further subcloning and sequencing based
      on different patterns from restriction analysis. Deduced amino acid analysis of
      possible ORFs revealed one novel gene encoding an enzyme belonging to glycosyl
      hydrolase family 43 (GH43), which is a GH family rarely found in metagenomic
      studies. The most notable finding is that this enzyme, designated as Biof1_09,
      shows dual activities, namely endocellulase and endoxylanase activities. Biof1_09
      showed greater than 50% of its activity under acidic conditions ranging from pH
      3.5 to 5.5 with a pH optimum of 4.5. The optimum temperature of this enzyme was
      between 45 and 55  degrees C with an optimum of 50  degrees C. The properties of
      Biof1_09 make this enzyme an attractive candidate for large-scale expression for
      use in lignocellulose degradation for various bioprocess applications, including
      bioethanol fermentation.

PMID- 24737297
TI  - Detection of K1 antigen of Escherichia coli rods isolated from pregnant women and
      neonates.
AB  - The K1 antigen is an important virulence determinant of Escherichia coli strains
      and has been shown to be associated particularly with neonatal meningitis,
      bacteraemia and septicaemia. Thus, its detection seems to be useful, especially
      in the case of E. coli strains isolated from pregnant women and newborns. In this
      study, the sensitivity and specificity of the latex agglutination test (Pastorex
      Meningitis) for identification of E. coli serogroup K1 were assessed, using PCR
      as the gold standard. Our results showed that consistency of results between
      latex agglutination test and PCR amounted to 98.5%. Therefore, Pastorex
      Meningitis is a good alternative to PCR and could be used for rapid K1 antigen
      detection, especially in local non-specialized laboratories with limited
      resources where PCR assay is not applied.

PMID- 24737298
TI  - Modeling the size- and shape-dependent cohesive energy of nanomaterials and its
      applications in heterogeneous systems.
AB  - Studying the properties of nanomaterials can help us to understand the nature of
      the particular behavior of small-scale materials and forecast new advanced
      functionalized materials. The cohesive energy, as one of the most important
      fundamental properties, is strongly connected to the unique properties of
      nanostructures. In this work, we establish a theoretical model to investigate the
      effects of size and shape on the cohesive energies of free and embedded
      nanoparticles based on thermodynamic concepts. It is found that the cohesive
      energy of free nanoparticles usually decreases as its size decreases. However,
      there are two distinct variations of embedded nanoparticles in heterogeneous
      systems. One is that the cohesive energy decreases with the decreasing size, and
      the other is that the cohesive energy increases as size decreases. The present
      modeling results and predictions are very consistent with experiments and other
      existing theoretical models, implying that the model could be expected to be a
      general approach to understand the cohesive energy of nanomaterials. 

PMID- 24737299
TI  - The length of anterior vaginal wall exposed to external pressure on maximal
      straining MRI: relationship to urogenital hiatus diameter, and apical and bladder
      location.
AB  - INTRODUCTION AND HYPOTHESIS: In cystoceles, the distal anterior vaginal wall
      (AVW) bulges out through the introitus and is no longer in contact with the
      posterior vaginal wall or perineal body, exposing the pressure differential
      between intra-abdominal pressure and atmospheric pressure. The goal of this study
      is to quantify the length of the exposed vaginal wall length and to investigate
      its relationship with other factors associated with the AVW support, such as most
      dependent bladder location, apical location, and hiatus diameter, demonstrating
      its key role in cystocele formation. METHODS: Fifty women were selected to
      represent a full spectrum of AVW support. Each underwent supine, dynamic MR
      imaging. Most dependent bladder location and apical location were measured
      relative to the average normal position on the mid-sagittal plane using the
      Pelvic Inclination Correction System . The length of the exposed AVW and the
      hiatus diameter were measured as well. The relationship between exposed AVW and
      most dependent bladder location, apical location, and hiatus diameter were
      examined. RESULTS: A bilinear relationship has been observed between exposed
      vaginal wall length and most dependent bladder location (R(2) = 0.91, P < 0.001).
      When the bladder descents up to the inflection point (about 4.4 cm away from its
      normal position), there is little change in the exposed AVW length. With further
      descent, the exposed vaginal wall length increases significantly, with a 2 cm
      increase in exposed AVW length for every additional 1 cm of drop bladder
      location. A similar but weaker bilinear relationship exists between exposed AVW
      and apical location. Exposed vaginal wall length is also highly correlated with
      hiatus diameter (R(2) = 0.85, P < 0.001). CONCLUSION: A bilinear relationship
      exists between exposed vaginal wall length and most dependent bladder location
      and apical location. It is when the bladder descent is beyond the inflection
      point that exposed vaginal wall length increases significantly.

PMID- 24737300
TI  - Prevalence, etiology and risk factors of pelvic organ prolapse in premenopausal
      primiparous women.
AB  - INTRODUCTION: The natural history of pelvic organ prolapse (POP) is poorly
      understood. We investigated the prevalence and risk factors of postnatal POP in
      premenopausal primiparous women and the associated effect of mode of delivery.
      METHODS: We conducted a prospective cohort study in a tertiary teaching hospital
      attending 9,000 deliveries annually. Collagen-diseases history and clinical
      assessment was performed in 202 primiparae at >= 1 year postnatally. Assessment
      included Pelvic Organ Prolapse Quantification (POP-Q) system, Beighton mobility
      score, 2/3D-transperineal ultrasound (US) and quantification of collagen type III
      levels. Association with POP was assessed using various statistical tests,
      including logistic regression, where results with p < 0.1 in univariate analysis
      were included in multivariate analysis. RESULTS: POP had a high prevalence:
      uterine prolapse 89 %, cystocele 90 %, rectocele 70 % and up to 65 % having grade
      two on POP-Q staging. The majority had multicompartment involvement, and 80 %
      were asymptomatic. POP was significantly associated with joint hypermobility,
      vertebral hernia, varicose veins, asthma and high collagen type III levels (p <
      0.05). In multivariate logistic regression, only levator ani muscle (LAM)
      avulsion was significant in selected cases (p < 0.05). Caesarean section (CS) was
      significantly protective against cystocele and rectocele but not for uterine
      prolapse. CONCLUSIONS: Mild to moderate POP has a very high prevalence in
      premenopausal primiparous women. There is a significant association between POP,
      collagen levels, history of collagen disease and childbirth-related pelvic floor
      trauma. These findings support a congenital contribution to POP etiology,
      especially for uterine prolapse; however, pelvic trauma seems to play paramount
      role. CS is significantly protective against some types of prolapse only.

PMID- 24737302
TI  - Radioprotective effect of N-acetyl-L-cysteine free radical scavenger on
      compressive mechanical properties of the gamma sterilized cortical bone of bovine
      femur.
AB  - Gamma sterilization of bone allografts is used as a gold standard method to
      provide safety against disease transmission. However, it is well documented that
      high dose levels of ionizing radiation can degrade bone mechanical properties.
      This effect, which is attributed to the formation of free radicals through
      radiolysis of the water content of collagen, can lead to post-implantation
      difficulties such as pre-failure and/or secondary fractures of bone allografts.
      Recently, treatment of irradiated allografts with free radical scavengers is used
      to protect them against radiation-induced damages. This study aimed to
      investigate the radioprotective role of N-acetyl-L-cysteine (NAC) during the
      gamma sterilization of the cortical bone of bovine femurs using the compressive
      test. Totally, 195 cubic specimens with a dimension of 5 * 5 * 3 cubic mm were
      divided into 13 groups including a control and 12 experimental groups exposed to
      18, 36, and 70 kGy at three different NAC concentrations (1.25, 12.5, and 25 mM
      for 18 kGy; 5, 50, and 100 mM for 36 kGy; 10, 100, and 200 mM for 70 kGy). The
      mechanical behavior of the sterilized specimens was studied using the uniaxial
      compressive test. The results indicated a concentration-dependent radioprotection
      effect of NAC on the plastic properties of the cortical bones. The concentration
      dependency of NAC was in turn related to radiation dose levels. In conclusion,
      treatment of bone specimens with a characteristic concentration of NAC during
      exposure to specific radiation dose levels can provide an efficient
      radioprotection window for preserving the mechanical stability of gamma
      sterilized allografts.

PMID- 24737301
TI  - A randomized controlled trial comparing three single-incision minislings for
      stress urinary incontinence.
AB  - INTRODUCTION AND HYPOTHESIS: Studies have observed a significant heterogeneity in
      efficacy data for single-incision minislings (SIMS) as surgical treatment for
      female urinary incontinence (UI). Our study aim was to test the hypothesis that
      different vaginal kits for SIMS have different long-term outcomes. METHODS: One
      hundred and twenty women with stress (SUI) or mixed (MUI) UI were enrolled in a
      multicenter randomized clinical trial (registration number NCT00751088) and
      treated with three different SIMS (Ajust, MiniArc, or TVT Secur System). Duration
      of follow-up was at least 24 months from surgery. The primary outcome was the
      subjective cure rate at 24 months from surgery; secondary outcomes were rates of
      total failure and reoperations for UI. RESULTS: At study end, no difference was
      detected between groups in terms of total subjective cure rate [21 (52.5%) vs. 26
      (65.0%) vs. 21 (52.5%), in Ajust, MiniArc, and TVT Secur System group,
      respectively; P = 0.412] or in terms of total failure rate [24 (60.0%) vs. 22
      (55.0 %) vs. 27 (67.5 %), in Ajust, MiniArc, and TVT Secur System group,
      respectively; P = 0.432]. The proportion of patients who received a second
      surgery for UI was also not significantly different between groups [13 (32.5%)
      vs. 10 (25.0%) vs. 13 (32.5%), in Ajust, MiniArc, and TVT Secur System,
      respectively; P = 0.831]. CONCLUSION: The long-term efficacy of SIMS does not
      differ between the vaginal kits examined.

PMID- 24737303
TI  - The effect of supercritical carbon dioxide sterilization on the anisotropy of
      bovine cortical bone.
AB  - Bone allografts are used to replace bone that has been removed or to augment bone
      tissue in a number of clinical scenarios. In order to minimize the risk of
      infection and immune response, the bone is delipidated and terminally sterilized
      prior to implantation. The optimal method for bone graft sterilization has been
      the topic of considerable research and debate. Recently, supercritical carbon
      dioxide (SCCO(2)) treatments have been shown to terminally sterilize bone against
      a range of bacteria and viruses. This study aimed to evaluate the effect of these
      SCCO(2) treatments on the anisotropic mechanical properties of cortical bone.
      Adult bovine cortical cubes were prepared and treated using SCCO(2) and a range
      of common processing additives (ethanol, peracetic acid and hydrogen peroxide).
      The bone was mechanically tested in uniaxial compression in the axial, radial and
      tangential orientations. Ultimate stress, strain, elastic modulus, energy and
      stiffness were evaluated. This study found that SCCO(2) treatment without
      additive did not alter the ultimate stress, stiffness or energy to failure
      depreciably in any orientation. The addition of sterilants peracetic acid and
      hydrogen peroxide also preserved mechanical function, with no deleterious effect
      on stress or stiffness. This study highlights the expediency of SCCO(2) treatment
      for bone allograft processing as terminal sterilization can be achieved while
      maintaining the intrinsic mechanical properties of the graft.

PMID- 24737304
TI  - The oncolytic adenovirus Delta24-RGD in combination with cisplatin exerts a
      potent anti-osteosarcoma activity.
AB  - Osteosarcoma is the most common malignant bone tumor in children and adolescents.
      The presence of metastases and the lack of response to conventional treatment are
      the major adverse prognostic factors. Therefore, there is an urgent need for new
      treatment strategies that overcome both of these problems. Our purpose was to
      elucidate whether the use of the oncolytic adenovirus Delta24-RGD alone or in
      combination with standard chemotherapy would be effective, in vitro and in vivo,
      against osteosarcoma. Our results showed that Delta24-RGD exerted a potent
      antitumor effect against osteosarcoma cell lines that was increased by the
      addition of cisplatin. Delta24-RGD osteosarcoma treatment resulted in autophagy
      in vitro that was further enhanced when combined with cisplatin. Of importance,
      administration of Delta24-RGD and/or cisplatin, in novel orthotopic and two lung
      metastatic models in vivo resulted in a significant reduction of tumor burden
      meanwhile maintaining a safe toxicity profile. Together, our data underscore the
      potential of Delta24-RGD to become a realistic therapeutic option for primary and
      metastatic pediatric osteosarcoma. Moreover, this study warrants a future
      clinical trial to evaluate the safety and efficacy of Delta24-RGD for this
      devastating disease.

PMID- 24737306
TI  - Quantitative blood oxygenation level-dependent (BOLD) response of the left
      ventricular myocardium to hyperoxic respiratory challenge at 1.5 and 3.0 T.
AB  - The aim of this study was to quantify the response of the myocardial transverse
      relaxation times (DeltaT2*) to hyperoxic respiratory challenge (HRC) at different
      field strengths in an intra-individual comparison of healthy volunteers and in a
      patient with coronary artery disease. Blood oxygenation level-dependent (BOLD)
      cardiovascular MR (CMR) data were acquired in 10 healthy volunteers (five women,
      five men; mean age, 29 +/- 3 years; range, 22-35 years) at 1.5 and 3.0 T. Medical
      air (21% O2 ), pure oxygen and carbogen (95% O2 , 5% CO2 ) were administered in a
      block-design temporal pattern to induce normoxia, hyperoxia and hyperoxic
      hypercapnia, respectively. Average T2* times were derived from measurements by
      two independent and blind readers in 16 standard myocardial segments on three
      short-axis slices per patient. Inter- and intra-reader correlations of T2*
      measurements were good [intra-class correlation coefficient (ICC) = 0.75 and ICC
      = 0.79, both p < 0.001]. During normoxia, the mean T2* times were 29.9 +/- 6.1 ms
      at 1.5 T and 27.1 +/- 6.6 ms at 3.0 T. Both hyperoxic gases induced significant
      (all p < 0.01) T2* increases (?T2* hyperoxia: 1.5 T, 12.7%; 3.0 T, 11.2%;
      hyperoxic hypercapnia: 1.5 T, 13.1%; 3.0 T, 17.7%). Analysis of variance (ANOVA)
      results indicated a significant (both p < 0.001) effect of the inhaled gases on
      the T2* times at both 1.5 T (F = 17.74) and 3.0 T (F = 39.99). With regard to the
      patient imaged at 1.5 T, HRC induced significant T2* increases during hyperoxia
      and hyperoxic hypercapnia in normal myocardial segments, whereas the T2* response
      was not significant in ischemic segments (p > 0.23). The myocardial ?T2* response
      to HRC can reliably be imaged and quantified with BOLD CMR at both 1.5 and 3.0 T.
      During HRC, hyperoxia and hyperoxic hypercapnia induce a significant increase in
      T2*, with ?T2* being largest at 3.0 T and during hyperoxic hypercapnia in normal
      myocardial segments.

PMID- 24737307
TI  - A new data preparation method based on clustering algorithms for diagnosis
      systems of heart and diabetes diseases.
AB  - The most important factors that prevent pattern recognition from functioning
      rapidly and effectively are the noisy and inconsistent data in databases. This
      article presents a new data preparation method based on clustering algorithms for
      diagnosis of heart and diabetes diseases. In this method, a new modified K-means
      Algorithm is used for clustering based data preparation system for the
      elimination of noisy and inconsistent data and Support Vector Machines is used
      for classification. This newly developed approach was tested in the diagnosis of
      heart diseases and diabetes, which are prevalent within society and figure among
      the leading causes of death. The data sets used in the diagnosis of these
      diseases are the Statlog (Heart), the SPECT images and the Pima Indians Diabetes
      data sets obtained from the UCI database. The proposed system achieved 97.87 %,
      98.18 %, 96.71 % classification success rates from these data sets.
      Classification accuracies for these data sets were obtained through using 10-fold
      cross-validation method. According to the results, the proposed method of
      performance is highly successful compared to other results attained, and seems
      very promising for pattern recognition applications.

PMID- 24737308
TI  - Lack of noncanonical RAS mutations in cytogenetically normal acute myeloid
      leukemia.
AB  - Transforming mutations in RAS genes are commonly found in human malignancies,
      including myeloid leukemias. To investigate the incidence, spectrum, and
      distribution of activating K- and N-RAS mutations in cytogenetically normal acute
      myeloid leukemia (CN-AML) patients, 204 CN-AML patients were screened. Activating
      K- and N-RAS mutations were detected in 3 of 204 (1.5 %) and 22 of 204 (10.8 %)
      CN-AML samples, respectively. RAS mutated patients presented with a lower
      percentage of bone marrow blasts (65 vs 80 %, P = 0.022). RAS mutations tended to
      occur with nucleophosmin-1 (NPM1) mutations (P = 0.079), and all three samples
      containing K-RAS mutations had concomitant NPM1 mutations. There was no
      significant overlap between K-RAS mutations and N-RAS, FLT3, CEBPA, IDH1/2, WT1
      or MLL mutations. RAS mutation status did not impact relapse-free or overall
      survival of CN-AML patients. In contrast to reports of noncanonical RAS mutations
      in other cancers, including some leukemia subtypes, we only observed K- and N-RAS
      mutations in codons 12, 13, or 61 in CN-AML samples. Our findings suggest that
      while K-RAS mutations are infrequent in CN-AML, activating K-RAS mutations may
      cooperate with mutated NPM1 to induce leukemia. 

PMID- 24737309
TI  - Normal CYP3A activity during arsenic trioxide therapy.

PMID- 24737310
TI  - The utility of routine postoperative upper gastrointestinal swallow studies
      following laparoscopic sleeve gastrectomy.
AB  - Laparoscopic sleeve gastrectomy (LSG) has grown in popularity in recent years for
      the treatment of morbid obesity. Controversy exists regarding the usefulness of
      upper gastrointestinal (UGI) swallow studies on the first postoperative day in
      detecting possible complications. The aim of our study was to determine the
      efficacy and cost benefit of routine UGI studies on the first postoperative day
      following LSG. We retrospectively reviewed the hospital's records to identify
      patients who underwent LSG between January 2012 and June 2013. All patients had
      iodine-based contrast swallow study on the first postoperative day. Reports from
      all imaging studies and medical files were retrospectively reviewed, and
      complications were recorded. The Institutional Review Board waived the
      requirement for informed consent. During the study period, 722 patients underwent
      LSG. Mean BMI was 43 kg/m(2) (range 25-70). Of the 722 UGI studies, 721 were
      normal. The 1 abnormal study showed complete obstruction due to an incarcerated
      hiatal hernia. Five patients presented with a leak (0.7%). UGI swallow studies
      failed to detect any of the leaks resulting in a sensitivity of 0%. All leaks
      were apparent on computed tomography (CT) scans on postoperative days 2, 5, 7,
      23, and 90. The total cost of the UGI swallow studies was $180,500. Performing
      routine UGI studies on the first postoperative day following LSG is clearly not
      cost beneficial. UGI contrast studies are not efficient to screen for suture line
      leaks. We recommend obtaining a CT scan when there is clinical suspicion for a
      complication.

PMID- 24737311
TI  - Is conservative management for gastric perforation secondary to intragastric
      balloon possible? Case report and review of literature.
AB  - Intragastric balloon (IGB) is one of the available options for the management of
      morbid obesity. The procedure is generally safe and of moderate efficacy in most
      of the cases. One of the reported complications of IGB is gastric perforation.
      The management of this complication is classically surgical. To our knowledge,
      conservative management for gastric perforation secondary to IGB has not been
      reported. A 27-year-old female patient presented with sudden abdominal pain in
      the left upper quadrant, 2 months after having an IGB placed. The provisional
      diagnosis was gastric perforation. Balloon extraction was performed and a
      conservative management of the gastric perforation was pursued successfully. We
      therefore propose that this sort of management might be adopted in carefully
      selected cases. 

PMID- 24737312
TI  - Hypoglycemia after Roux-en-Y gastric bypass: the BOLD experience.

PMID- 24737313
TI  - Small molecule screen for candidate antimalarials targeting Plasmodium Kinesin-5.
AB  - Plasmodium falciparum and vivax are responsible for the majority of malaria
      infections worldwide, resulting in over a million deaths annually. Malaria
      parasites now show measured resistance to all currently utilized drugs. Novel
      antimalarial drugs are urgently needed. The Plasmodium Kinesin-5 mechanoenzyme is
      a suitable "next generation" target. Discovered via small molecule screen
      experiments, the human Kinesin-5 has multiple allosteric sites that are
      "druggable." One site in particular, unique in its sequence divergence across all
      homologs in the superfamily and even within the same family, exhibits exquisite
      drug specificity. We propose that Plasmodium Kinesin-5 shares this allosteric
      site and likewise can be targeted to uncover inhibitors with high specificity. To
      test this idea, we performed a screen for inhibitors selective for Plasmodium
      Kinesin-5 ATPase activity in parallel with human Kinesin-5. Our screen of nearly
      2000 compounds successfully identified compounds that selectively inhibit both P.
      vivax and falciparum Kinesin-5 motor domains but, as anticipated, do not impact
      human Kinesin-5 activity. Of note is a candidate drug that did not biochemically
      compete with the ATP substrate for the conserved active site or disrupt the
      microtubule-binding site. Together, our experiments identified MMV666693 as a
      selective allosteric inhibitor of Plasmodium Kinesin-5; this is the first
      identified protein target for the Medicines of Malaria Venture validated
      collection of parasite proliferation inhibitors. This work demonstrates that
      chemical screens against human kinesins are adaptable to homologs in disease
      organisms and, as such, extendable to strategies to combat infectious disease. 

PMID- 24737314
TI  - Life in a sea of oxygen.

PMID- 24737315
TI  - Endorepellin evokes autophagy in endothelial cells.
AB  - Endorepellin, the C-terminal fragment of the heparan sulfate proteoglycan
      perlecan, possesses angiostatic activity via dual receptor antagonism, through
      concurrent binding to the alpha2beta1 integrin and vascular endothelial growth
      factor receptor 2 (VEGFR2). Here, we discovered that soluble endorepellin induced
      autophagy in endothelial cells by modulating the expression of Beclin 1, LC3, and
      p62, three established autophagic markers. Moreover, endorepellin evoked
      expression of the imprinted tumor suppressor gene Peg3 and its co-localization
      with Beclin 1 and LC3 in autophagosomes, suggesting a major role for this gene in
      endothelial cell autophagy. Mechanistically, endorepellin induced autophagy by
      down-regulating VEGFR2 via the two LG1/2 domains, whereas the C-terminal LG3
      domain, the portion responsible for binding the alpha2beta1 integrin, was
      ineffective. Endorepellin also induced transcriptional activity of the BECN1
      promoter in endothelial cells, and the VEGFR2-specific tyrosine kinase inhibitor,
      SU5416, blocked this effect. Finally, we found a correlation between endorepellin
      evoked inhibition of capillary morphogenesis and enhanced autophagy. Thus, we
      have identified a new role for this endogenous angiostatic fragment in inducing
      autophagy through a VEGFR2-dependent but alpha2beta1 integrin-independent
      pathway. This novel mechanism specifically targets endothelial cells and could
      represent a promising new strategy to potentiate the angiostatic effect of
      endorepellin and perhaps other angiostatic matrix proteins. 

PMID- 24737316
TI  - Structural basis of pharmacological chaperoning for human beta-galactosidase.
AB  - GM1 gangliosidosis and Morquio B disease are autosomal recessive diseases caused
      by the defect in the lysosomal beta-galactosidase (beta-Gal), frequently related
      to misfolding and subsequent endoplasmic reticulum-associated degradation.
      Pharmacological chaperone (PC) therapy is a newly developed molecular therapeutic
      approach by using small molecule ligands of the mutant enzyme that are able to
      promote the correct folding and prevent endoplasmic reticulum-associated
      degradation and promote trafficking to the lysosome. In this report, we describe
      the enzymological properties of purified recombinant human beta-Gal(WT) and two
      representative mutations in GM1 gangliosidosis Japanese patients, beta-Gal(R201C)
      and beta-Gal(I51T). We have also evaluated the PC effect of two competitive
      inhibitors of beta-Gal. Moreover, we provide a detailed atomic view of the
      recognition mechanism of these compounds in comparison with two structurally
      related analogues. All compounds bind to the active site of beta-Gal with the
      sugar-mimicking moiety making hydrogen bonds to active site residues. Moreover,
      the binding affinity, the enzyme selectivity, and the PC potential are strongly
      affected by the mono- or bicyclic structure of the core as well as the
      orientation, nature, and length of the exocyclic substituent. These results
      provide understanding on the mechanism of action of beta-Gal selective
      chaperoning by newly developed PC compounds. 

PMID- 24737317
TI  - Syntaxin13 expression is regulated by mammalian target of rapamycin (mTOR) in
      injured neurons to promote axon regeneration.
AB  - Injured peripheral neurons successfully activate intrinsic signaling pathways to
      enable axon regeneration. We have previously shown that dorsal root ganglia (DRG)
      neurons activate the mammalian target of rapamycin (mTOR) pathway following
      injury and that this activity enhances their axon growth capacity. mTOR plays a
      critical role in protein synthesis, but the mTOR-dependent proteins enhancing the
      regenerative capacity of DRG neurons remain unknown. To identify proteins whose
      expression is regulated by injury in an mTOR-dependent manner, we analyzed the
      protein composition of DRGs from mice in which we genetically activated mTOR and
      from mice with or without a prior nerve injury. Quantitative label-free mass
      spectrometry analyses revealed that the injury effects were correlated with mTOR
      activation. We identified a member of the soluble N-ethylmaleimide-sensitive
      factor attachment protein receptor (SNARE) family of proteins, syntaxin13, whose
      expression was increased by injury in an mTOR-dependent manner. Increased
      syntaxin13 levels in injured nerves resulted from local protein synthesis and not
      axonal transport. Finally, knockdown of syntaxin13 in cultured DRG neurons
      prevented axon growth and regeneration. Together, these data suggest that
      syntaxin13 translation is regulated by mTOR in injured neurons to promote axon
      regeneration. 

PMID- 24737318
TI  - A novel subtype of astrocytes expressing TRPV4 (transient receptor potential
      vanilloid 4) regulates neuronal excitability via release of gliotransmitters.
AB  - Astrocytes play active roles in the regulation of synaptic transmission. Neuronal
      excitation can evoke Ca(2+) transients in astrocytes, and these Ca(2+) transients
      can modulate neuronal excitability. Although only a subset of astrocytes appears
      to communicate with neurons, the types of astrocytes that can regulate neuronal
      excitability are poorly characterized. We found that ~30% of astrocytes in the
      brain express transient receptor potential vanilloid 4 (TRPV4), indicating that
      astrocytic subtypes can be classified on the basis of their expression patterns.
      When TRPV4(+) astrocytes are activated by ligands such as arachidonic acid, the
      activation propagates to neighboring astrocytes through gap junctions and by ATP
      release from the TRPV4(+) astrocytes. After activation, both TRPV4(+) and TRPV4(
      ) astrocytes release glutamate, which acts as an excitatory gliotransmitter to
      increase synaptic transmission through type 1 metabotropic glutamate receptor
      (mGluR). Our results indicate that TRPV4(+) astrocytes constitute a novel subtype
      of the population and are solely responsible for initiating excitatory
      gliotransmitter release to enhance synaptic transmission. We propose that
      TRPV4(+) astrocytes form a core of excitatory glial assembly in the brain and
      function to efficiently increase neuronal excitation in response to endogenous
      TRPV4 ligands. 

PMID- 24737319
TI  - Reciprocal changes in phosphorylation and methylation of mammalian brain sodium
      channels in response to seizures.
AB  - Voltage-gated sodium (Nav) channels initiate action potentials in brain neurons
      and are primary therapeutic targets for anti-epileptic drugs controlling neuronal
      hyperexcitability in epilepsy. The molecular mechanisms underlying abnormal Nav
      channel expression, localization, and function during development of epilepsy are
      poorly understood but can potentially result from altered posttranslational
      modifications (PTMs). For example, phosphorylation regulates Nav channel gating,
      and has been proposed to contribute to acquired insensitivity to anti-epileptic
      drugs exhibited by Nav channels in epileptic neurons. However, whether changes in
      specific brain Nav channel PTMs occur acutely in response to seizures has not
      been established. Here, we show changes in PTMs of the major brain Nav channel,
      Nav1.2, after acute kainate-induced seizures. Mass spectrometry-based proteomic
      analyses of Nav1.2 purified from the brains of control and seizure animals
      revealed a significant down-regulation of phosphorylation at nine sites,
      primarily located in the interdomain I-II linker, the region of Nav1.2 crucial
      for phosphorylation-dependent regulation of activity. Interestingly, Nav1.2 in
      the seizure samples contained methylated arginine (MeArg) at three sites. These
      MeArgs were adjacent to down-regulated sites of phosphorylation, and Nav1.2
      methylation increased after seizure. Phosphorylation and MeArg were not found
      together on the same tryptic peptide, suggesting reciprocal regulation of these
      two PTMs. Coexpression of Nav1.2 with the primary brain arginine
      methyltransferase PRMT8 led to a surprising 3-fold increase in Nav1.2 current.
      Reciprocal regulation of phosphorylation and MeArg of Nav1.2 may underlie changes
      in neuronal Nav channel function in response to seizures and also contribute to
      physiological modulation of neuronal excitability. 

PMID- 24737320
TI  - Artemin, a member of the glial cell line-derived neurotrophic factor family of
      ligands, is HER2-regulated and mediates acquired trastuzumab resistance by
      promoting cancer stem cell-like behavior in mammary carcinoma cells.
AB  - Previous studies have demonstrated that Artemin (ARTN) functions as a cancer stem
      cell (CSC) and metastatic factor in mammary carcinoma. Herein, we report that
      ARTN mediates acquired resistance to trastuzumab in HER2-positive mammary
      carcinoma cells. Ligands that increase HER2 activity increased ARTN expression in
      HER2-positive mammary carcinoma cells, whereas trastuzumab inhibited ARTN
      expression. Forced expression of ARTN decreased the sensitivity of HER2-positive
      mammary carcinoma cells to trastuzumab both in vitro and in vivo. Conversely,
      siRNA-mediated depletion of ARTN enhanced trastuzumab efficacy. Cells with
      acquired resistance to trastuzumab exhibited increased ARTN expression, the
      depletion of which restored trastuzumab sensitivity. Trastuzumab resistance
      produced an increased CSC population concomitant with enhanced mammospheric
      growth. ARTN mediated the enhancement of the CSC population by increased BCL-2
      expression, and the CSC population in trastuzumab-resistant cells was abrogated
      upon inhibition of BCL-2. Hence, we conclude that ARTN is one mediator of
      acquired resistance to trastuzumab in HER2-positive mammary carcinoma cells. 

PMID- 24737321
TI  - Altered nucleosome positioning at the transcription start site and deficient
      transcriptional initiation in Friedreich ataxia.
AB  - Most individuals with Friedreich ataxia (FRDA) are homozygous for an expanded GAA
      triplet repeat (GAA-TR) mutation in intron 1 of the FXN gene, which results in
      deficiency of FXN transcript. Consistent with the expanded GAA-TR sequence as a
      cause of variegated gene silencing, evidence for heterochromatin has been
      detected in intron 1 in the immediate vicinity of the expanded GAA-TR mutation in
      FRDA. Transcriptional deficiency in FRDA is thought to result from deficient
      elongation through the expanded GAA-TR sequence because of repeat-proximal
      heterochromatin and abnormal DNA structures adopted by the expanded repeat. There
      is also evidence for deficient transcriptional initiation in FRDA, but its
      relationship to the expanded GAA-TR mutation remains unclear. We show that
      repressive chromatin extends from the expanded GAA-TR in intron 1 to the upstream
      regions of the FXN gene, involving the FXN transcriptional start site. Using a
      chromatin accessibility assay and a high-resolution nucleosome occupancy assay,
      we found that the major FXN transcriptional start site, which is normally in a
      nucleosome-depleted region, is rendered inaccessible by altered nucleosome
      positioning in FRDA. Consistent with the altered epigenetic landscape the FXN
      gene promoter, a typical CpG island promoter, was found to be in a
      transcriptionally non-permissive state in FRDA. Both metabolic labeling of
      nascent transcripts and an unbiased whole transcriptome analysis revealed a
      severe deficiency of transcriptional initiation in FRDA. Deficient
      transcriptional initiation, and not elongation, is the major cause of FXN
      transcriptional deficiency in FRDA, and it is related to the spread of repressive
      chromatin from the expanded GAA-TR mutation. 

PMID- 24737322
TI  - Crystal structure of the transcriptional regulator Rv0678 of Mycobacterium
      tuberculosis.
AB  - Recent work demonstrates that the MmpL (mycobacterial membrane protein large)
      transporters are dedicated to the export of mycobacterial lipids for cell wall
      biosynthesis. An MmpL transporter frequently works with an accessory protein,
      belonging to the MmpS (mycobacterial membrane protein small) family, to transport
      these key virulence factors. One such efflux system in Mycobacterium tuberculosis
      is the MmpS5-MmpL5 transporter. The expression of MmpS5-MmpL5 is controlled by
      the MarR-like transcriptional regulator Rv0678, whose open reading frame is
      located downstream of the mmpS5-mmpL5 operon. To elucidate the structural basis
      of Rv0678 regulation, we have determined the crystal structure of this regulator,
      to 1.64 A resolution, revealing a dimeric two-domain molecule with an
      architecture similar to members of the MarR family of transcriptional regulators.
      Rv0678 is distinct from other MarR regulators in that its DNA-binding and
      dimerization domains are clustered together. These two domains seemingly
      cooperate to bind an inducing ligand that we identified as 2-stearoylglycerol,
      which is a fatty acid glycerol ester. The structure also suggests that the
      conformational change leading to substrate-mediated derepression is primarily
      caused by a rigid body rotational motion of the entire DNA-binding domain of the
      regulator toward the dimerization domain. This movement results in a
      conformational state that is incompatible with DNA binding. We demonstrate using
      electrophoretic mobility shift assays that Rv0678 binds to the mmpS5-mmpL5, mmpS4
      mmpL4, and the mmpS2-mmpL2 promoters. Binding by Rv0678 was reversed upon the
      addition of the ligand. These findings provide new insight into the mechanisms of
      gene regulation in the MarR family of regulators. 

PMID- 24737323
TI  - Tristetraprolin represses estrogen receptor alpha transactivation in breast
      cancer cells.
AB  - Estrogen receptor alpha (ERalpha) mediates the effects of 17beta-estradiol (E2)
      in normal mammary gland, and it is a key participant in breast cancer tumor
      development. ERalpha transactivation activity is mediated by the synergistic
      interaction of two domains designated AF1 and AF2. The function of AF2 is to
      recruit coactivator and corepressor proteins that allow ERalpha to oscillate
      between the roles of transcriptional activator and repressor. In contrast, the
      mechanism responsible for AF-1 transcriptional activity is not completely
      understood. In this study, we identified tristetraproline (TTP) as a novel
      ERalpha-associated protein. TTP expression in MCF7 cells repressed ERalpha
      transactivation and reduced MCF7 cell proliferation and the ability of the cells
      to form tumors in a mouse model. We show that TTP transcriptional activity is
      mediated through its recruitment to the promoter region of ERalpha target genes
      and its interaction with histone deacetylases, in particular with HDAC1. TTP
      expression attenuates the coactivating activity of SRC-1, suggesting that
      exchange between TTP and other coactivators may play an important role in fine
      tuning ERalpha transactivation. These results indicate that TTP acts as a bona
      fide ERalpha corepressor and suggest that this protein may be a contributing
      factor in the development of E2-dependent tumors in breast cancer. 

PMID- 24737324
TI  - DNA damage induces the accumulation of Tiam1 by blocking beta-TrCP-dependent
      degradation.
AB  - The Rac1/JNK cascade plays important roles in DNA damage-induced apoptosis.
      However, how this cascade is activated upon DNA damage remains to be fully
      understood. We show here that, in untreated cells, Tiam1, a Rac1-specific guanine
      nucleotide exchange factor, is phosphorylated by casein kinase 1 (CK1) at its C
      terminus, leading to Skp, Cullin, F-box-containing(beta-TrCP) recognition,
      ubiquitination, and proteasome-mediated degradation. Upon DNA-damaging anticancer
      drug treatment, CK1/beta-TrCP-mediated Tiam1 degradation is abolished, and the
      accumulated Tiam1 contributes to downstream activation of Rac1/JNK. Consistently,
      tumor cells overexpressing Tiam1 are hypersensitive to DNA-damaging drug
      treatment. In xenograft mice, Tiam1-high cells are more susceptible to
      doxorubicin treatment. Thus, our results uncover that inhibition of proteasome
      mediated Tiam1 degradation is an upstream event leading to Rac1/JNK activation
      and cell apoptosis in response to DNA-damaging drug treatment. 

PMID- 24737325
TI  - Inactivation of the transcription factor GLI1 accelerates pancreatic cancer
      progression.
AB  - The role of GLI1 in pancreatic tumor initiation promoting the progression of
      preneoplastic lesions into tumors is well established. However, its function at
      later stages of pancreatic carcinogenesis remains poorly understood. To address
      this issue, we crossed the gli1 knock-out (GKO) animal with cre-dependent
      pancreatic activation of oncogenic kras concomitant with loss of the tumor
      suppressor tp53 (KPC). Interestingly, in this model, GLI1 played a tumor
      protective function, where survival of GKO/KPC mice was reduced compared with KPC
      littermates. Both cohorts developed pancreatic cancer without significant
      histopathological differences in survival studies. However, analysis of mice
      using ultrasound-based imaging at earlier time points showed increased tumor
      burden in GKO/KPC mice. These animals have larger tumors, decreased body weight,
      increased lactate dehydrogenase production, and severe leukopenia. In vivo and in
      vitro expression studies identified FAS and FAS ligand (FASL) as potential
      mediators of this phenomenon. The FAS/FASL axis, an apoptotic inducer, plays a
      role in the progression of pancreatic cancer, where its expression is usually
      lost or significantly reduced in advanced stages of the disease. Chromatin
      immunoprecipitation and reporter assays identified FAS and FASL as direct targets
      of GLI1, whereas GKO/KPC mice showed lower levels of this ligand compared with
      KPC animals. Finally, decreased levels of apoptosis were detected in tumor tissue
      in the absence of GLI1 by TUNEL staining. Together, these findings define a novel
      pathway regulated by GLI1 controlling pancreatic tumor progression and provide a
      new theoretical framework to help with the design and analysis of trials
      targeting GLI1-related pathways. 

PMID- 24737326
TI  - Architecture of the nitric-oxide synthase holoenzyme reveals large conformational
      changes and a calmodulin-driven release of the FMN domain.
AB  - Nitric-oxide synthase (NOS) is required in mammals to generate NO for regulating
      blood pressure, synaptic response, and immune defense. NOS is a large homodimer
      with well characterized reductase and oxygenase domains that coordinate a
      multistep, interdomain electron transfer mechanism to oxidize l-arginine and
      generate NO. Ca(2+)-calmodulin (CaM) binds between the reductase and oxygenase
      domains to activate NO synthesis. Although NOS has long been proposed to adopt
      distinct conformations that alternate between interflavin and FMN-heme electron
      transfer steps, structures of the holoenzyme have remained elusive and the CaM
      bound arrangement is unknown. Here we have applied single particle electron
      microscopy (EM) methods to characterize the full-length of the neuronal isoform
      (nNOS) complex and determine the structural mechanism of CaM activation. We have
      identified that nNOS adopts an ensemble of open and closed conformational states
      and that CaM binding induces a dramatic rearrangement of the reductase domain.
      Our three-dimensional reconstruction of the intact nNOS-CaM complex reveals a
      closed conformation and a cross-monomer arrangement with the FMN domain rotated
      away from the NADPH-FAD center, toward the oxygenase dimer. This work captures,
      for the first time, the reductase-oxygenase structural arrangement and the CaM
      dependent release of the FMN domain that coordinates to drive electron transfer
      across the domains during catalysis. 

PMID- 24737327
TI  - Molecular basis of the general base catalysis of an alpha/beta-hydrolase
      catalytic triad.
AB  - The serine-histidine-aspartate triad is well known for its covalent, nucleophilic
      catalysis in a diverse array of enzymatic transformations. Here we show that its
      nucleophilicity is shielded and its catalytic role is limited to being a specific
      general base by an open-closed conformational change in the catalysis of (1R,6R)
      2-succinyl-6-hydroxy-2,4-cyclohexadiene-1-carboxylate synthase (or MenH), a
      typical alpha/beta-hydrolase fold enzyme in the vitamin K biosynthetic pathway.
      This enzyme is found to adopt an open conformation without a functional triad in
      its ligand-free form and a closed conformation with a fully functional catalytic
      triad in the presence of its reaction product. The open-to-closed conformational
      transition involves movement of half of the alpha-helical cap domain, which
      causes extensive structural changes in the alpha/beta-domain and forces the side
      chain of the triad histidine to adopt an energetically disfavored gauche
      conformation to form the functional triad. NMR analysis shows that the inactive
      open conformation without a triad prevails in ligand-free solution and is
      converted to the closed conformation with a properly formed triad by the reaction
      product. Mutation of the residues crucial to this open-closed transition either
      greatly decreases or completely eliminates the enzyme activity, supporting an
      important catalytic role for the structural change. These findings suggest that
      the open-closed conformational change tightly couples formation of the catalytic
      triad to substrate binding to enhance the substrate specificities and
      simultaneously shield the nucleophilicity of the triad, thus allowing it to
      expand its catalytic power beyond the nucleophilic catalysis. 

PMID- 24737328
TI  - The LA loop as an important regulatory element of the HtrA (DegP) protease from
      Escherichia coli: structural and functional studies.
AB  - Bacterial HtrAs are serine proteases engaged in extracytoplasmic protein quality
      control and are required for the virulence of several pathogenic species. The
      proteolytic activity of HtrA (DegP) from Escherichia coli, a model prokaryotic
      HtrA, is stimulated by stressful conditions; the regulation of this process is
      mediated by the LA, LD, L1, L2, and L3 loops. The precise mechanism of action of
      the LA loop is not known due to a lack of data concerning its three-dimensional
      structure as well as its mode of interaction with other regulatory elements. To
      address these issues we generated a theoretical model of the three-dimensional
      structure of the LA loop as per the resting state of HtrA and subsequently
      verified its correctness experimentally. We identified intra- and intersubunit
      contacts that formed with the LA loops; these played an important role in
      maintaining HtrA in its inactive conformation. The most significant proved to be
      the hydrophobic interactions connecting the LA loops of the hexamer and polar
      contacts between the LA' (the LA loop on an opposite subunit) and L1 loops on
      opposite subunits. Disturbance of these interactions caused the stimulation of
      HtrA proteolytic activity. We also demonstrated that LA loops contribute to the
      preservation of the integrity of the HtrA oligomer and to the stability of the
      monomer. The model presented in this work explains the regulatory role of the LA
      loop well; it should also be applicable to numerous Enterobacteriaceae pathogenic
      species as the amino acid sequences of the members of this bacterial family are
      highly conserved. 

PMID- 24737329
TI  - Reconciling the structural attributes of avian antibodies.
AB  - Antibodies are high value therapeutic, diagnostic, biotechnological, and research
      tools. Combinatorial approaches to antibody discovery have facilitated access to
      unique antibodies by surpassing the diversity limitations of the natural
      repertoire, exploitation of immune repertoires from multiple species, and
      tailoring selections to isolate antibodies with desirable biophysical attributes.
      The V-gene repertoire of the chicken does not utilize highly diverse sequence and
      structures, which is in stark contrast to the mechanism employed by humans, mice,
      and primates. Recent exploitation of the avian immune system has generated high
      quality, high affinity antibodies to a wide range of antigens for a number of
      therapeutic, diagnostic and biotechnological applications. Furthermore, extensive
      examination of the amino acid characteristics of the chicken repertoire has
      provided significant insight into mechanisms employed by the avian immune system.
      A paucity of avian antibody crystal structures has limited our understanding of
      the structural consequences of these uniquely chicken features. This paper
      presents the crystal structure of two chicken single chain fragment variable
      (scFv) antibodies generated from large libraries by phage display against
      important human antigen targets, which capture two unique CDRL1 canonical classes
      in the presence and absence of a non-canonical disulfide constrained CDRH3. These
      structures cast light on the unique structural features of chicken antibodies and
      contribute further to our collective understanding of the unique mechanisms of
      diversity and biochemical attributes that render the chicken repertoire of
      particular value for antibody generation. 

PMID- 24737330
TI  - Mitochondrial tRNA 5'-editing in Dictyostelium discoideum and Polysphondylium
      pallidum.
AB  - Mitochondrial tRNA (mt-tRNA) 5'-editing was first described more than 20 years
      ago; however, the first candidates for 5'-editing enzymes were only recently
      identified in a eukaryotic microbe (protist), the slime mold Dictyostelium
      discoideum. In this organism, eight of 18 mt-tRNAs are predicted to be edited
      based on the presence of genomically encoded mismatched nucleotides in their
      aminoacyl-acceptor stem sequences. Here, we demonstrate that mt-tRNA 5'-editing
      occurs at all predicted sites in D. discoideum as evidenced by changes in the
      sequences of isolated mt-tRNAs compared with the expected sequences encoded by
      the mitochondrial genome. We also identify two previously unpredicted editing
      events in which G-U base pairs are edited in the absence of any other genomically
      encoded mismatches. A comparison of 5'-editing in D. discoideum with 5'-editing
      in another slime mold, Polysphondylium pallidum, suggests organism-specific
      idiosyncrasies in the treatment of U-G/G-U pairs. In vitro activities of putative
      D. discoideum editing enzymes are consistent with the observed editing reactions
      and suggest an overall lack of tRNA substrate specificity exhibited by the repair
      component of the editing enzyme. Although the presence of terminal mismatches in
      mt-tRNA sequences is highly predictive of the occurrence of mt-tRNA 5'-editing,
      the variability in treatment of U-G/G-U base pairs observed here indicates that
      direct experimental evidence of 5'-editing must be obtained to understand the
      complete spectrum of mt-tRNA editing events in any species. 

PMID- 24737332
TI  - Variability in the use of invasive services: sign of poor quality of care or an
      opportunity to improve care?

PMID- 24737331
TI  - Selective antibody intervention of Toll-like receptor 4 activation through Fc
      gamma receptor tethering.
AB  - Inflammation is mediated mainly by leukocytes that express both Toll-like
      receptor 4 (TLR4) and Fc gamma receptors (FcgammaR). Dysregulated activation of
      leukocytes via exogenous and endogenous ligands of TLR4 results in a large number
      of inflammatory disorders that underlie a variety of human diseases. Thus,
      differentially blocking inflammatory cells while sparing structural cells, which
      are FcgammaR-negative, represents an elegant strategy when targeting the
      underlying causes of human diseases. Here, we report a novel tethering mechanism
      of the Fv and Fc portions of anti-TLR4 blocking antibodies that achieves
      increased potency on inflammatory cells. In the presence of ligand (e.g.
      lipopolysaccharide (LPS)), TLR4 traffics into glycolipoprotein microdomains,
      forming concentrated protein platforms that include FcgammaRs. This clustering
      produces a microenvironment allowing anti-TLR4 antibodies to co-engage TLR4 and
      FcgammaRs, increasing their avidity and thus substantially increasing their
      inhibitory potency. Tethering of antibodies to both TLR4 and FcgammaRs proves
      valuable in ameliorating inflammation in vivo. This novel mechanism of action
      therefore has the potential to enable selective intervention of relevant cell
      types in TLR4-driven diseases. 

PMID- 24737333
TI  - Identifying patients who do not benefit from transcatheter aortic valve
      replacement.

PMID- 24737334
TI  - Routine pressure wire assessment at time of diagnostic angiography: is it ready
      for prime time?

PMID- 24737335
TI  - Venous interventions.

PMID- 24737336
TI  - Early aneurysm formation after everolimus-eluting stent implantation.

PMID- 24737337
TI  - Percutaneous bicaval valve implantation for transcatheter treatment of tricuspid
      regurgitation: clinical observations and 12-month follow-up.

PMID- 24737338
TI  - Letter by Grbel et al regarding article, "administration of a loading dose has no
      additive effect on platelet aggregation during the switch from ongoing
      clopidogrel treatment to ticagrelor in patients with acute coronary syndrome".

PMID- 24737340
TI  - Cationic conjugated polymers for discrimination of microbial pathogens.

PMID- 24737341
TI  - MicroRNA binding sites in the coding region of mRNAs: extending the repertoire of
      post-transcriptional gene regulation.
AB  - It is well established that microRNAs (miRNAs) induce mRNA degradation by binding
      to 3' untranslated regions (UTRs). The functionality of sites in the coding
      domain sequence (CDS), on the other hand, remains under discussion. Such sites
      have limited impact on target mRNA abundance and recent work suggests that miRNAs
      bind in the CDS to inhibit translation. What then could be the regulatory
      benefits of translation inhibition through CDS targeting compared to mRNA
      degradation following 3' UTR binding? We propose that these domain-dependent
      effects serve to diversify the functional repertoire of post-transcriptional gene
      expression control. Possible regulatory benefits may include tuning the time
      scale and magnitude of post-transcriptional regulation, regulating protein
      abundance depending on or independently of the cellular state, and regulation of
      the protein abundance of alternative splice variants. Finally, we review emerging
      evidence that these ideas may generalize to RNA-binding proteins beyond miRNAs
      and Argonaute proteins. 

PMID- 24737342
TI  - Incorporating polyoxometalates into a porous MOF greatly improves its selective
      adsorption of cationic dyes.
AB  - Various polyoxometalates (POMs) were successfully immobilized to the mesoporous
      coordination polymer MIL-101 resulting in a series of POM-MOF composite materials
      POM@MIL-101 (POM = K4PW11VO40, H3PW12O40, K4SiW12O40). These materials were
      synthesized by a simple one-pot reaction of Keggin POMs, tetramethylammonium
      hydroxide (TMAH), terephthalic acid (H2bdc), and Cr(3+) ions. XRD, FTIR,
      thermogravimetric analyses (TG), inductively coupled plasma (ICP) spectrometry,
      and energy-dispersive X-ray spectroscopy (EDX) collectively confirmed the
      successful combination of POMs and the porous framework. Further, these
      composites POM@MIL-101 with different loading of POMs were achieved by variation
      of the POM dosage. Notably, the uptake capacity of MIL-101 towards organic
      pollutants in aqueous solution was significantly improved by immobilization of
      hydrophilic POMs into cages of MIL-101. An uptake capacity of 371 mg g(-1),
      comparable to that of the graphene oxide sponges, and much higher than that of
      the commercial activated carbon, was achieved at room temperature in 5 min when
      dipping 20 mg PW11V@MIL-101 in the methylene blue (MB) solution (100 mL of 100 mg
      L(-1) MB solution). Further study revealed that the POM@MIL-101 composite
      materials not only exhibited a fast adsorption rate towards dye molecules, but
      also possessed of selective adsorption ability of the cationic dyes in
      wastewater. For example, the adsorption efficiency of PW11V@MIL-101 (10 mg)
      towards MB (100 mL of 10 mg L(-1)) could reach 98 % in the initial 5 min, and it
      could capture MB dye molecules from the binary mixture of the MB and MO with
      similar size. Also, the POM@MIL-101 materials could be readily recycled and
      reused, and no POM leached in the dye adsorption process.

PMID- 24737343
TI  - Population pharmacokinetic and pharmacodynamic analysis of tremelimumab in
      patients with metastatic melanoma.
AB  - Tremelimumab, a fully human monoclonal antibody specific for human cytotoxic T
      lymphocyte-associated antigen 4, has been studied in clinical trials. We have
      reported the results of population pharmacokinetics for tremelimumab in 654
      metastatic melanoma patients. Population estimates (inter-individual variability
      [IIV]) for pharmacokinetic parameters in a final model were clearance (CL), 0.26
      L/day (31.8%) and central volume of distribution, 3.97 L (20.4%). CL was faster
      in males, patients with higher values of creatinine clearance and endogenous
      immunoglobulin, and patients with relatively poor baseline prognostic factors. No
      dose adjustment was needed based on the magnitude of the change of CL (<30%). The
      association of CL and overall survival (OS) was investigated. In a Phase 3 trial
      evaluating tremelimumab as first-line-treatment, median OS for the 147 patients
      in the fast-CL group (>= median CL value) was 9.6 months versus 15.8 months for
      the 146 patients in the slow-CL group (<median CL value). Multiple Cox
      proportional hazard regression models were constructed to evaluate the
      association between CL and OS adjusting for the effects of baseline prognostic
      covariates between two CL groups. The analysis showed statistically significant
      association between CL and OS (P < .05). Results suggest that higher or more
      frequent dosing should be considered in future trials.

PMID- 24737344
TI  - Signal transduction mechanism of the NZW type IL-10R1 and the effect on B
      lymphocyte function.
AB  - The present study aimed to investigate the signal transduction mechanism of the
      NZW type interleukin (IL)-10R1 and the effect on the function of B lymphocytes.
      Vectors for the expression of wild-type, NZW and G1146A IL-10R1 were constructed
      and transfected into Ba/F3 cells. The cell proliferation curve was determined
      using an MTT assay. CD32 and leukocyte-endothelial cell adhesion molecule 1
      (LECAM-1) expression levels were assessed using flow cytometry. The
      phosphorylation of Janus kinase 1 (Jak1), tyrosine kinase 2 (Tyk2) and signal
      transducer and activator of transcription 3 (Stat3) were measured by western blot
      analysis. As compared with wild-type IL-10R1 cells, the proliferation ability of
      NZW IL-10R1 cells was increased following stimulation with IL-10, which was even
      greater for G1146A cells. CD32 levels in NZW IL-10R1 cells were lower, while the
      expression of LECAM-1 was higher compared with wild-type IL-10R1 cells, which was
      also observed for G1146A cells. The phosphorylation levels of Jak1 and Stat3 in
      NZW IL-10R1 and G1146A IL-10R1 cells were significantly lower compared with the
      wild-type IL-10R1 cells. However, the phosphorylation levels in the three cell
      types were not significantly different. In conclusion, the deficiency in Jak1
      Stat3 signal transduction in NZW IL-10R1 cells induces a loss in the inhibition
      ability of proliferation and activation as well as a migration tendency of B
      lymphocytes, which is hypothesized to be associated with the occurrence and
      development of the autoimmune disease systemic lupus erythematosus (SLE). 

PMID- 24737345
TI  - Synthesis and biological evaluation of dual action cyclo-RGD/SMAC mimetic
      conjugates targeting alpha(v)beta(3)/alpha(v)beta(5) integrins and IAP proteins.
AB  - The rational design, synthesis and in vitro biological evaluation of dual action
      conjugates 11-13, containing a tumour targeting, integrin alphavbeta3/alphavbeta5
      ligand portion and a pro-apoptotic SMAC mimetic portion (cyclo-RGD/SMAC mimetic
      conjugates) are reported. The binding strength of the two separate units is
      generally maintained by these dual action conjugates. In particular, the
      connection between the separate units (anchor points on each unit; nature, length
      and stability of the linker) influences the activity of each portion against its
      molecular targets (integrins alphavbeta3/alphavbeta5 for cyclo-RGD, IAP proteins
      for SMAC mimetics). Each conjugate portion tolerates different substitutions
      while preserving the binding affinity for each target. 

PMID- 24737346
TI  - A GG allele of 3'-side AKT1 SNP is associated with decreased AKT1 activation and
      better prognosis of gastric cancer.
AB  - PURPOSE: v-akt Murine thymoma viral oncogene homolog (AKT) pathway is critically
      involved in cancer cell growth, invasion, and survival. We examined the
      correlation between the genetic variations in molecules of AKT pathway and
      clinical outcomes of gastric cancer. PATIENTS AND METHODS: Six single nucleotide
      polymorphisms (SNPs) located in the four core genes of AKT pathway, namely the
      PIK3CA, PTEN, AKT1, and mTOR, were determined in 221 patients with stage T2 and
      T3 gastric cancer. Additionally, the activation of AKT1 in gastric cancer tissues
      was examined by immunostaining. The correlation between SNPs, AKT activation, and
      the progress of gastric cancer was analyzed after an average of 51-month follow
      up. RESULTS: The overall recurrence and survival rate in this study group were
      54.8 and 46.6 %, respectively. The recurrence rate was reduced 30.4 %, and the
      survival rate was increased 33.7 % in patients with GG allele of a 3'-side AKT1
      SNP (rs2498804). Significantly, GG allele was associated with lower AKT1
      activation in gastric cancer tissues. On the contrary, CC allele of PTEN
      (rs701848) was associated with the increased risk of recurrence (hazard ratio
      [HR] 2.06, 95 % CI 1.19-3.58) and patient death (HR 2.01, 95 % CI 1.15-3.53).
      CONCLUSIONS: The genetic variants in the PI3K/PTEN/AKT especially the GG allele
      in 3' side of AKT1 are closely related to clinical outcomes of gastric cancer.

PMID- 24737347
TI  - BRCA1 and BRCA2 germline mutations are frequently demonstrated in both high-risk
      pancreatic cancer screening and pancreatic cancer cohorts.
AB  - BACKGROUND: Approximately 10% of pancreatic ductal adenocarcinoma (PDAC) is due
      to a genetic predisposition, including the breast and ovarian cancer syndrome
      germline mutations BRCA1 and BRCA2. Knowledge of specific genetic mutations
      predisposing to PDAC may enable risk stratification, early detection, and the
      development of effective screening and surveillance programs. In the current
      study, the authors attempted to determine the diagnostic yield of testing for
      BRCA1/2 germline mutations in a PDAC screening cohort and a PDAC cohort referred
      for genetic testing. METHODS: Patients in a high-risk PDAC prevention and
      genetics program or those with a personal history of PDAC who were referred for
      genetic evaluation underwent testing for BRCA1/2 germline mutations. Clinical
      BRCA1/2 genetic testing included testing for the 3 Ashkenazi Jewish founder
      mutations or BRCA1/2 comprehensive testing. RESULTS: A total of 37 patients
      without PDAC underwent BRCA1/2 testing at the study institution. Genetic testing
      identified 7 patients who were BRCA1/2 carriers for a yield of 18.9%. Six
      patients carried Ashkenazi Jewish founder mutations (3 with BRCA1 and 3 with
      BRCA2), and 1 patient was found to have a BRCA2 mutation on comprehensive
      testing. Thirty-two patients with PDAC underwent BRCA1/2 genetic testing. Five
      patients had Ashkenazi Jewish founder mutations (2 with BRCA1 and 3 with BRCA2),
      and 2 patients were found to have BRCA2 mutations on comprehensive testing. The
      diagnostic yield was 7 of 32 patients (21.9%). CONCLUSIONS: BRCA1/2 testing is
      useful in PDAC risk stratification and alters risk assignment and screening
      recommendations for mutation-positive patients and their families. Clinical
      BRCA1/2 testing should be considered in patients of Ashkenazi Jewish descent with
      a personal history or family history of PDAC, even in the absence of a family
      history of breast and ovarian cancer.

PMID- 24737348
TI  - An initial validation of the Italian Mishel Uncertainty Illness Scale (MUIS) for
      relapsing remitting multiple sclerosis patients.
AB  - Multiple sclerosis is a chronic disease, likely to condition patients' daily
      living and quality of life: given the unpredictability of frequency and severity
      of the attacks, patients experience a high level of uncertainty. While there have
      been many analyses whose purpose was to monitor multiple sclerosis (MS) patients'
      quality of life, the role of uncertainty, that is peculiar to the disease, has
      not been adequately considered so far. The present study is aimed at filling this
      gap by validating for Italian MS patients the Mishel's Uncertainty Illness Scale
      (MUIS). The MUIS has been developed in the USA context in order to assess four
      aspects of uncertainty: ambiguity, complexity, inconsistency and
      unpredictability. It has been largely applied in the cancer, cardiac and chronic
      illness population. Data employed in this study have been collected at two
      neurological centres in Messina (IRCCS Centro Studi Neurolesi "Bonino Pulejo" and
      Policlinico di Messina) in the first semester of 2013 and refer to 120 MS
      patients. The confirmatory factor analysis described in this study validates two
      of the four dimensions of MUIS, namely ambiguity and inconsistency. The
      validation, though partial, of the MUIS, allows the use of this instrument in
      studies investigating quality of life for Italian patients.

PMID- 24737349
TI  - Chrysin ameliorates diabetes-associated cognitive deficits in Wistar rats.
AB  - Chrysin (CH) is an important natural plant flavonoid and possesses diverse
      pharmacological activities. Our present investigations aimed to assess the
      neuroprotection of CH against diabetes-associated cognitive decline (DACD) in a
      rat model of diabetes and exploring its potential mechanism. Diabetic model was
      induced by intraperitoneal injection of streptozotocin. Then, they were treated
      with vehicle or CH by doses of 30 and 100 mg/kg for 26 days. Learning and memory
      function was evaluated by Morris water maze test. The oxidative indicators
      [malondialdehyde (MDA), catalase (CAT), superoxide dismutase (SOD) and
      glutathione (GSH)], NF-kappaB p65 unit, TNF-alpha, IL-1beta, IL-6 and caspase-3
      were measured in cerebral cortex and hippocampus using corresponding commercial
      kits. The diabetic rats showed marked reductions in body weight, percentage of
      time spent in target quadrant and number of times of crossing platform, coupled
      with increases in plasma glucose levels, escape latency, mean path length and
      oxidative stress (increased MDA level and decreased CAT and SOD as well as
      reduced GSH), NF-kappaB p65 unit, TNF-alpha, IL-1beta, IL-6 and caspase-3 in
      cerebral cortex and hippocampus. Moreover, CH supplement dramatically reversed
      the corresponding behavioral, biochemical and molecular alterations in diabetes.
      The alterations of swimming speed among different groups were not observed after
      CH adminstration. In conclusion, our current work discloses that CH remarkably
      alleviates DACD and suggests that oxidative stress, inflammation and apoptotic
      cascades are linked with diabetes-associated cognitive deficits. These findings
      point toward the therapeutic potential of CH in DACD.

PMID- 24737353
TI  - Our English coasts (strayed sheep): William Holman Hunt.

PMID- 24737350
TI  - A family with distal myopathy with rimmed vacuoles associated with
      thrombocytopenia.

PMID- 24737354
TI  - CDC: Hospital antibiotic use promotes resistance: checklist can improve
      practices.

PMID- 24737355
TI  - WHO: More than 7 million air pollution deaths each year.

PMID- 24737356
TI  - IOM: Military psychological interventions lack evidence.

PMID- 24737357
TI  - Some progress in effort to reduce hospital-acquired infections.

PMID- 24737365
TI  - A piece of my mind. Miracle.

PMID- 24737366
TI  - Maternal body mass index and the risk of fetal death, stillbirth, and infant
      death: a systematic review and meta-analysis.
AB  - IMPORTANCE: Evidence suggests that maternal obesity increases the risk of fetal
      death, stillbirth, and infant death; however, the optimal body mass index (BMI)
      for prevention is not known. OBJECTIVE: To conduct a systematic review and meta
      analysis of cohort studies of maternal BMI and risk of fetal death, stillbirth,
      and infant death. DATA SOURCES: The PubMed and Embase databases were searched
      from inception to January 23, 2014. STUDY SELECTION: Cohort studies reporting
      adjusted relative risk (RR) estimates for fetal death, stillbirth, or infant
      death by at least 3 categories of maternal BMI were included. DATA EXTRACTION:
      Data were extracted by 1 reviewer and checked by the remaining reviewers for
      accuracy. Summary RRs were estimated using a random-effects model. MAIN OUTCOMES
      AND MEASURES: Fetal death, stillbirth, and neonatal, perinatal, and infant death.
      RESULTS: Thirty eight studies (44 publications) with more than 10,147 fetal
      deaths, more than 16,274 stillbirths, more than 4311 perinatal deaths, 11,294
      neonatal deaths, and 4983 infant deaths were included. The summary RR per 5-unit
      increase in maternal BMI for fetal death was 1.21 (95% CI, 1.09-1.35; I2 = 77.6%;
      n = 7 studies); for stillbirth, 1.24 (95% CI, 1.18-1.30; I2 = 80%; n = 18
      studies); for perinatal death, 1.16 (95% CI, 1.00-1.35; I2 = 93.7%; n = 11
      studies); for neonatal death, 1.15 (95% CI, 1.07-1.23; I2 = 78.5%; n = 12
      studies); and for infant death, 1.18 (95% CI, 1.09-1.28; I2 = 79%; n = 4
      studies). The test for nonlinearity was significant in all analyses but was most
      pronounced for fetal death. For women with a BMI of 20 (reference standard for
      all outcomes), 25, and 30, absolute risks per 10,000 pregnancies for fetal death
      were 76, 82 (95% CI, 76-88), and 102 (95% CI, 93-112); for stillbirth, 40, 48
      (95% CI, 46-51), and 59 (95% CI, 55-63); for perinatal death, 66, 73 (95% CI, 67
      81), and 86 (95% CI, 76-98); for neonatal death, 20, 21 (95% CI, 19-23), and 24
      (95% CI, 22-27); and for infant death, 33, 37 (95% CI, 34-39), and 43 (95% CI, 40
      47), respectively. CONCLUSIONS AND RELEVANCE: Even modest increases in maternal
      BMI were associated with increased risk of fetal death, stillbirth, and neonatal,
      perinatal, and infant death. Weight management guidelines for women who plan
      pregnancies should take these findings into consideration to reduce the burden of
      fetal death, stillbirth, and infant death.

PMID- 24737367
TI  - Fibromyalgia: a clinical review.
AB  - IMPORTANCE: Fibromyalgia is present in as much as 2% to 8% of the population, is
      characterized by widespread pain, and is often accompanied by fatigue, memory
      problems, and sleep disturbances. OBJECTIVE: To review the epidemiology,
      pathophysiology, diagnosis, and treatment of fibromyalgia. EVIDENCE REVIEW: The
      medical literature on fibromyalgia was reviewed from 1955 to March 2014 via
      MEDLINE and the Cochrane Central Registry of Controlled Trials, with an emphasis
      on meta-analyses and contemporary evidence-based treatment guidelines. Treatment
      recommendations are based on the most recent evidence-based guidelines from the
      Canadian Pain Society and graded from 1 to 5 based on the level of available
      evidence. FINDINGS: Numerous treatments are available for managing fibromyalgia
      that are supported by high-quality evidence. These include nonpharmacological
      therapies (education, exercise, cognitive behavioral therapy) and pharmacological
      therapies (tricyclics, serotonin norepinephrine reuptake inhibitors, and
      gabapentinoids). CONCLUSIONS AND RELEVANCE: Fibromyalgia and other "centralized"
      pain states are much better understood now than ever before. Fibromyalgia may be
      considered as a discrete diagnosis or as a constellation of symptoms
      characterized by central nervous system pain amplification with concomitant
      fatigue, memory problems, and sleep and mood disturbances. Effective treatment
      for fibromyalgia is now possible.

PMID- 24737368
TI  - Parental perspectives on adolescent hearing loss.

PMID- 24737369
TI  - A nodular protuberance on the hard palate.

PMID- 24737370
TI  - Variation in rates of autoimmune thyroid disease by race/ethnicity in US military
      personnel.

PMID- 24737371
TI  - Dopamine vs nesiritide for acute heart failure with renal dysfunction.

PMID- 24737372
TI  - Dopamine vs nesiritide for acute heart failure with renal dysfunction--reply.

PMID- 24737373
TI  - Lag time to benefit for preventive therapies.

PMID- 24737374
TI  - Lag time to benefit for preventive therapies.

PMID- 24737375
TI  - Lag time to benefit for preventive therapies--reply.

PMID- 24737378
TI  - Fibromyalgia syndrome: an emerging but controversial condition.

PMID- 24737379
TI  - JAMA patient page. Fibromyalgia.

PMID- 24737380
TI  - mTOR pathway as a potential target in a subset of human medulloblastoma.
AB  - As mammalian Target of Rapamycin (mTOR) plays role in protein synthesis and
      metabolism, mTOR pathway activation is involved in the pathogenesis of several
      types of tumors. Our aim was to elucidate its role in medulloblastoma in terms of
      prognosis and as a therapeutic target. Members of activated mTOR complex 1
      (mTORC1) pathway, phospho-mTOR (p-mTOR) and phospho-S6 (p-S6) were examined by
      immunohistochemistry in formalin fixed paraffin embedded samples of 40 patients
      with medulloblastoma, and results were compared to clinical features and survival
      of patients. In proliferation assays, Daoy and UW228-2 medulloblastoma cell lines
      were tested by rapamycin, an mTORC1 inhibitor, and NVP-BEZ235, a dual mTOR and
      phosphatidylinositol 3-kinase (PI3K) inhibitor, each in monotherapy and in
      combination with cytostatic drugs (cisplatin, etoposide). Components of mTORC1
      and mTORC2 complexes were also examined in these cell lines. Neither presence of
      p-mTOR (32.5 %) nor p-S6 (32.5 %) correlated with age, gender or histological
      subtype. In 22.5 % of cases simultaneous expression of p-mTOR and p-S6 was shown.
      Kaplan-Meier analysis showed inferior survival of patients expressing both marker
      proteins, but it was not statistically significant, probably due to low case
      number. UW228-2 cells had greater sensitivity to mTOR inhibitors, possibly due to
      its higher mTORC1 specific protein expression levels, compared to Daoy cells. In
      both cell lines antiproliferative effect of cytostatic drugs was significantly
      enhanced by mTOR inhibitors (p < 0.05). Based on our in vitro and
      clinicopathological studies mTOR inhibitors may have a role in the future
      treatment of a subset of patients with medulloblastoma.

PMID- 24737382
TI  - Extended phase graphs: dephasing, RF pulses, and echoes - pure and simple.
AB  - The extended phase graph (EPG) concept represents a powerful tool for depicting
      and understanding the magnetization response of a broad variety of MR sequences.
      EPGs focus on echo generation as well as on classification and use a Fourier
      based magnetization description in terms of "configurations states". The effect
      of gradients, radiofrequency (RF) pulses, relaxation, and motion phenomena during
      the MR sequence is characterized as the action of a few matrix operations on
      these configuration states. Thus, the EPG method allows for fast and precise
      quantitation of echo intensities even if several gradients and RF pulses are
      applied. EPG diagrams aid in the comprehension of different types of echoes and
      their corresponding echo time. Despite its several benefits in regard to a large
      number of problems and issues, researchers and users still often refrain from
      applying EPGs. It seems that "phase graphing" is still seen as a kind of "magic."
      The present review investigates the foundation of EPGs and sheds light on
      prerequisites for adding more advanced phenomena such as diffusion. The links
      between diagrams and calculations are discussed. A further focus is on
      limitations and simplifications as well recent extensions within the EPG concept.
      To make the review complete, representative software for EPG coding is provided.

PMID- 24737381
TI  - Human papilloma virus, DNA methylation and microRNA expression in cervical cancer
      (Review).
AB  - Cancer is a complex disease caused by genetic and epigenetic abnormalities that
      affect gene expression. The progression from precursor lesions to invasive
      cervical cancer is influenced by persistent human papilloma virus (HPV)
      infection, which induces changes in the host genome and epigenome. Epigenetic
      alterations, such as aberrant miRNA expression and changes in DNA methylation
      status, favor the expression of oncogenes and the silencing of tumor-suppressor
      genes. Given that some miRNA genes can be regulated through epigenetic
      mechanisms, it has been proposed that alterations in the methylation status of
      miRNA promoters could be the driving mechanism behind their aberrant expression
      in cervical cancer. For these reasons, we assessed the relationship among HPV
      infection, cellular DNA methylation and miRNA expression. We conclude that
      alterations in the methylation status of protein-coding genes and various miRNA
      genes are influenced by HPV infection, the viral genotype, the physical state of
      the viral DNA, and viral oncogenic risk. Furthermore, HPV induces deregulation of
      miRNA expression, particularly at loci near fragile sites. This deregulation
      occurs through the E6 and E7 proteins, which target miRNA transcription factors
      such as p53. 

PMID- 24737383
TI  - A triple approach for diagnostic assessment of endoscopic ultrasound-guided fine
      needle aspiration in pancreatic solid masses and lymph nodes.
AB  - BACKGROUND AND AIMS: Endoscopic ultrasound (EUS)-guided fine needle aspiration
      (FNA) has been becoming the standard tool for acquiring pancreatic lesion tissue.
      However, a single cytologic or histologic evaluation is not satisfactory for
      diagnosis. In this study, we evaluated the diagnostic yield of EUS-FNA for
      pancreatic solid masses and intra-abdominal lymph nodes using a triple approach.
      METHODS: This study included patients undergoing evaluation for a solid
      pancreatic mass (n = 59) or intra-abdominal lymph nodes (n = 16) using EUS-FNA
      with a 22- or 25-gauge (G) needle, respectively. The specimens from each pass
      were analyzed by on-site cytology using Diff-Quick stain, cytology using
      Papanicolaou stain, and histology with immunohistochemical (IHC) staining.
      RESULTS: A total of 75 patients (49 males; mean age; 63.7 years) were included.
      The median number of needle pass for diagnosis of malignancy was 2.0, and there
      was no technical failure. The diagnostic accuracies with on-site cytology,
      cytology using Papanicolaou staining, and histology were 70.7, 80.0, and 80.0 %,
      respectively. The diagnostic accuracy using a triple approach was significantly
      greater than cytology using Papanicolaou staining alone (94.7 vs. 80.0 %; p =
      0.007). In patients with malignant lesions, cytology identified 12 of 71 (16.9 %)
      malignant lesions that were not diagnosed by histology using IHC, and histology
      identified six (8.5 %) malignant lesions that were not diagnosed by cytology.
      CONCLUSION: On-site cytopathologic evaluation combined with cytologic and
      histologic analysis with IHC stain for one-pass specimen is considered to be able
      to increase the overall accuracy of EUS-FNA in pancreatic solid masses and lymph
      nodes.

PMID- 24737385
TI  - Is pneumonectomy using video-assisted thoracic surgery the way to go? Study of
      data from the Japanese Association for Thoracic Surgery.
AB  - BACKGROUND: The number of pneumonectomies performed has been decreasing every
      year. That decrease is the result of changes in distribution of histological
      type, stage, and tumor location. To investigate the results of pneumonectomies
      performed on lung cancer patients in Japan over a period of 15 years, data
      reported by the Japanese Association for Thoracic Surgery were analyzed. METHODS:
      All data shown in the table were derived from official records reported in Japan.
      Mortality refers to hospital death rather than 30-day death, to more precisely
      evaluate the safety of the operations. RESULTS: (1) The number of sleeve
      lobectomies did not increase. (2) The operative mortality rate with
      pneumonectomies did not fall. In 2011, the rate of hospital deaths among
      pneumonectomy patients rose to 3.9% and worsened to 5.3% in 2012, which was more
      than twice that of 30-day death, despite an improvement in results as a whole.
      (3) The incidence of lethal bronchopleural fistula showed very little
      improvement, declining from 11.7 to 9.6%. (4) In 2012, VATS was used in 13.1% of
      all pneumonectomy patients. That figure stood at only 0.5% in 1997. CONCLUSION:
      Regarding pneumonectomies performed in Japan during the period analyzed, use of
      the less-invasive approach increased but bronchopleural fistula was still a major
      complication. The rate of hospital deaths among pneumonectomy patients worsened 2
      years in a row. What is of critical importance is not the choice of approach-
      VATS or open thoracotomy--but the surgeon's efforts to find a chance to perform
      lung-saving surgery.

PMID- 24737386
TI  - Osteoporosis Assessment Questionnaire-Physical Function (OPAQ-PF): a
      psychometrically validated osteoporosis-targeted patient reported outcome measure
      of daily activities of physical function.
AB  - The purpose of this study was to evaluate the measurement properties of the
      Osteoporosis Assessment Questionnaire-Physical Functioning (OPAQ-PF). Based on
      this study, the OPAQ-PF has confirmed unidimensionality and acceptable
      reliability, construct validity, and sensitivity to change in a recent
      fracture/no recent fracture osteoporosis sample. METHODS: Dimensionality was
      established through exploratory and confirmatory factor analysis. Patients
      completed three patient reported outcome (PRO) measures and four performance
      based measures (PBMs) at baseline to enable an evaluation of construct validity.
      Patients without a recent fracture completed the OPAQ-PF 2 weeks after baseline
      to enable an evaluation of test-retest reliability. Ability to detect change and
      interpretation of change were investigated following completion of the OPAQ-PF 12
      and 24 weeks postbaseline by patients with a recent fracture. RESULTS: A
      prospective psychometric validation study in 144 postmenopausal women, with
      moderate to severe osteoporosis, 37 of whom had experienced a recent fragility
      fracture (<6 weeks). Unidimensionality was established for the OPAQ-PF by factor
      analysis. The OPAQ-PF had good internal consistency (alpha = 0.974) and test
      retest reliability (mean intraclass correlation coefficient (ICC) 0.993. The OPAQ
      PF differentiated between patients with/without recent fracture, and by severity
      of osteoarthritis; it correlated strongly with hypothesized-related scales and
      PBMs (r > 0.3, p < 0.001). Ability to detect change was established with high
      correlations between changes in OPAQ-PF score and changes in global concept
      scores in recent fracture patients (r >= 0.6, 24-week change). Effect size of
      change on OPAQ-PF score increased by level of global change (p < 0.001). Anchor
      based methods identified an OPAQ-PF change of 10 at an individual patient level
      and 20 at a group level as meaningful to patients. CONCLUSIONS: The OPAQ-PF has
      confirmed unidimensionality and acceptable reliability, construct validity, and
      sensitivity to change in a recent fracture/no recent fracture osteoporosis
      sample.

PMID- 24737387
TI  - Immunolocalization of antimicrobial and cytoskeletal components in the serous
      glands of human sinonasal mucosa.
AB  - Secretory cells in the seromucous glands of paranasal sinuses secrete
      antibacterial proteins for innate immune mucosal integrity. We studied the
      localization of antimicrobial and cytoskeletal components of the human seromucous
      glands and respiratory epithelium of the maxillary sinus and the ethmoidal cells
      by immunohistochemical methods. The presence of a variety of defense proteins
      such as lysozyme, lactoferrin, cathelicidin, and defensin-1, -2, -3 point to a
      crucial role in the immune defense for the respiratory tract. Cytoskeletal
      proteins such as actin, myosin 2, cytokeratin 7 and 19, alpha- and beta-tubulin,
      investigated for the first time in glands of paranasal sinuses, showed a stronger
      expression at the apical and lateral cell membrane. The localization of the
      cytoskeletal proteins might point to their participation in exocrine secretory
      processes and stabilizing effects.

PMID- 24737388
TI  - Influence of physical activity on bone strength in children and adolescents: a
      systematic review and narrative synthesis.
AB  - A preponderance of evidence from systematic reviews supports the effectiveness of
      weight-bearing exercises on bone mass accrual, especially during the growing
      years. However, only one systematic review (limited to randomized controlled
      trials) examined the role of physical activity (PA) on bone strength. Thus, our
      systematic review extended the scope of the previous review by including all PA
      intervention and observational studies, including organized sports participation
      studies, with child or adolescent bone strength as the main outcome. We also
      sought to discern the skeletal elements (eg, mass, structure, density) that
      accompanied significant bone strength changes. Our electronic-database, forward,
      and reference searches yielded 14 intervention and 23 observational studies that
      met our inclusion criteria. We used the Effective Public Health Practice Project
      (EPHPP) tool to assess the quality of studies. Due to heterogeneity across
      studies, we adopted a narrative synthesis for our analysis and found that bone
      strength adaptations to PA were related to maturity level, sex, and study
      quality. Three (of five) weight-bearing PA intervention studies with a strong
      rating reported significantly greater gains in bone strength for the intervention
      group (3% to 4%) compared with only three significant (of nine) moderate
      intervention studies. Changes in bone structure (eg, bone cross-sectional area,
      cortical thickness, alone or in combination) rather than bone mass most often
      accompanied significant bone strength outcomes. Prepuberty and peripuberty may be
      the most opportune time for boys and girls to enhance bone strength through PA,
      although this finding is tempered by the few available studies in more mature
      groups. Despite the central role that muscle plays in bones' response to loading,
      few studies discerned the specific contribution of muscle function (or
      surrogates) to bone strength. Although not the focus of the current review, this
      seems an important consideration for future studies.

PMID- 24737389
TI  - MR-monitored focused ultrasound using the acoustic-coupling water bath as an
      intrinsic high-mode dielectric resonator.
AB  - The conventional set-up for MR-monitored focused ultrasound surgery includes a
      piezoelectric transducer and an acoustic-coupling water bath integrated into the
      MR patient table; a large surface RF coil is placed close to the patient or,
      alternatively, the body coil is used as the MR receiver. Potential disadvantages
      of this approach are that the body coil has low sensitivity because of its low
      filling factor and the local RF coil can interfere with and cause reflections of
      the ultrasound irradiation. In this article, a completely new approach is
      presented, in which an MR transmit/receive coil is not needed at all. Instead,
      the dimensions of the water bath are adjusted so that a high-order dielectric
      mode is excited, resulting in efficient MR excitation and reception at the
      transducer focal point. An example of monitoring ultrasound-mediated heating in a
      phantom is shown on a 7-T human system, although the new method can also be
      applied at lower fields.

PMID- 24737390
TI  - Silk protein lithography as a route to fabricate sericin microarchitectures.
AB  - Photolithographic fabrication via a "silk sericin photoresist" is used to form
      precise protein microstructures directly and rapidly on a variety of substrates.
      High-resolution and fidelity architectures in two and three dimensions with line
      widths down to 1 MUm are formed. Photo-crosslinked protein structures provide
      structural iridescence and guide cell adhesion with precise spatial control. 

PMID- 24737394
TI  - Asymmetric allylation of ketones and subsequent tandem reactions catalyzed by a
      novel polymer-supported titanium-BINOLate complex.
AB  - By using a novel, simple, and convenient synthetic route, enantiopure 6-ethynyl
      BINOL (BINOL = 1,1-binaphthol) was synthesized and anchored to an
      azidomethylpolystyrene resin through a copper-catalyzed alkyne-azide
      cycloaddition (CuAAC) reaction. The polystyrene (PS)-supported BINOL ligand was
      converted into its diisopropoxytitanium derivative in situ and used as a
      heterogeneous catalyst in the asymmetric allylation of ketones. The catalyst
      showed good activity and excellent enantioselectivity, typically matching the
      results obtained in the corresponding homogeneous reaction. The allylation
      reaction mixture could be submitted to epoxidation by simple treatment with tert
      butyl hydroperoxide (TBHP), and the tandem asymmetric allylation epoxidation
      process led to a highly enantioenriched epoxy alcohol with two adjacent
      quaternary centers as a single diastereomer. A tandem asymmetric
      allylation/Pauson-Khand reaction was also performed, involving simple treatment
      of the allylation reaction mixture with Co2(CO)8/N-methyl morpholine N-oxide.
      This cascade process resulted in the formation of two diastereomeric tricyclic
      enones in high yields and enantioselectivities.

PMID- 24737391
TI  - Role of HCMV miR-UL70-3p and miR-UL148D in overcoming the cellular apoptosis.
AB  - The studies into the pathophysiology of viral miRNAs are still in infancy; the
      interspecies regulation at the miRNA level fuels the spark of the investigation
      into the repertoire of virus-host interactions. Reports pertaining to the viral
      miRNAs role in modulating/evading the host immune response are surging up; we
      initiated this in silico study to speculate the role of human cytomegalovirus
      (HCMV)-encoded miRNAs on human antiviral mechanisms such as apoptosis and
      autophagy. The results indicate that both the above mechanisms were targeted by
      the HCMV miRNAs, located in the unique long region of the HCMV genome. The
      proapoptotic genes MOAP1, PHAP, and ERN1 are identified to be the potential
      targets for the miR-UL70-3p and UL148D, respectively. The ERN1 gene plays a role
      in the initiation of Endoplasmic reticulum stress-induced apoptosis as well as
      autophagosome formation. This study shows that HCMV employs its miRNA repertoire
      for countering the cellular apoptosis and autophagy, particularly the
      mitochondrial-dependent intrinsic pathway of apoptosis. In addition, the homology
      studies reveal no HCMV miRNA bears sequence homology with human miRNAs. 

PMID- 24737393
TI  - Notch signaling in prostate cancer: a moving target.
AB  - INTRODUCTION: By regulating cell fate, proliferation, and survival, Notch pathway
      signaling provides critical input into differentiation, organization, and
      function of multiple tissues. Notch signaling is also becoming an increasingly
      recognized feature in malignancy, including prostate cancer, where it may play
      oncogenic or tumor suppressive roles. METHODS: Based on an electronic literature
      search from 2000 to 2013 we identified, summarized, and integrated published
      research on Notch signaling dynamics in prostate homeostasis and prostate cancer.
      RESULTS: In benign prostate, Notch controls the differentiation state and
      architecture of the gland. In prostate cancer, similar features correlate with
      lethal potential and may be influenced by Notch. Increased Notch1 can confer a
      survival advantage on prostate cancer cells, and levels of Notch family members,
      such as Jagged2, Notch3, and Hes6 increase with higher cancer grade. However,
      Notch signaling can also antagonize growth and survival of both benign and
      malignant prostate cells, possibly through antagonistic effects of the Notch
      target HEY1 on androgen receptor function. DISCUSSION: Notch signaling can
      dramatically influence prostate development and disease. Determining the cellular
      contexts where Notch promotes or suppresses prostate growth could open
      opportunities for diagnostic and therapeutic interventions.

PMID- 24737395
TI  - Three new sesquiterpene lactones from Inula britannica.
AB  - One new 1,10-secoeudesmanolide (1), two eudesmanolides (2 and 3), together with
      nine known compounds (4-12) were isolated from the aerial parts of Inula
      britannica. The structures of the new compounds were elucidated by detailed
      spectroscopic analysis, including HRESIMS and 2D-NMR spectroscopic method. In
      addition, compounds 1-4 were tested for their inhibitory effects against LPS
      induced NO production in RAW264.7 macrophages. 

PMID- 24737396
TI  - Improved production, purification and bioactivity of a polysaccharide from
      submerged cultured Ganoderma lucidum.
AB  - Polysaccharides from Ganoderma lucidum showed multiple biological activities,
      such as immuno-modulating, antitumor, antioxidant, and hepatoprotective activity,
      etc. Adlay oil was added into the media to enhance polysaccharide production by
      submerged culture of G. lucidum in this work. The results revealed the optimal
      concentration of adlay oil was 1.5 % for polysaccharide production of G. lucidum.
      Analysis of the polysaccharide components confirmed that no novel components were
      biosynthesized by the addition of adlay oil. The main fraction of extracellular
      polysaccharide, GLEP-2, was isolated from the submerged culture broth of G.
      lucidum by ethanol precipitation, filtration, DEAE cellulose-52 and Sepharose CL
      6B chromatography. GLEP-2, which was composed of glucose, galactose, mannose,
      arabinose, and rhamnose in a ratio of 332:55:32:13:3 respectively, had an average
      molecular weight of ~2.08 * 10(4) Da. The bioactivity tests demonstrated that
      GLEP-2 enhanced the T lymphocyte proliferation significantly at a concentration
      of 200 MUg/mL and B lymphocyte proliferation at lower concentrations of 50
      MUg/mL. The results suggest polysaccharides from the submerged culture of G.
      lucidum are potential candidates for further development and possible commercial
      applications, especially in the pharmaceutical and functional foods industries.

PMID- 24737398
TI  - Identification of European mosquito species by MALDI-TOF MS.
AB  - MALDI-TOF MS profiling has proved to be efficient for arthropod identification at
      the species level. However, prior to entomological monitoring, the reference
      spectra database should cover relevant species. Here, 74 specimens were field
      collected from 11 mosquito species captured in two distinct European areas and
      used either to increment our database or for blind tests. Misidentification was
      not noted, underlining the power of this approach. Nevertheless, three out of the
      26 specimens used for the blind test did not reach the significant identification
      threshold value set, attributed to lower spectral quality. In the future, the
      quality control spectra parameters need to be defined to avoid not achieving
      significant threshold identification. 

PMID- 24737397
TI  - Independent oncogenic and therapeutic significance of phosphatase PRL-3 in FLT3
      ITD-negative acute myeloid leukemia.
AB  - BACKGROUND: Internal tandem duplication of FMS-like tyrosine kinase (FLT3-ITD) is
      well known to be involved in acute myeloid leukemia (AML) progression, but FLT3
      ITD-negative AML cases account for 70% to 80% of AML, and the mechanisms
      underlying their pathology remain unclear. This study identifies protein tyrosine
      phophatase PRL-3 as a key mediator of FLT3-ITD-negative AML. METHODS: A total of
      112 FLT3-ITD-negative AML patients were sampled between 2010 and 2013, and the
      occurrence of PRL-3 hyperexpression in FLT3-ITD-negative AML was evaluated by
      multivariate probit regression analysis. Overexpression or depletion of
      endogenous PRL-3 expression with the specific small interfering RNAs was
      performed to investigate the role of PRL-3 in AML progression. Xenograft models
      were also used to confirm the oncogenic role of PRL-3. RESULTS: Compared to
      healthy donors, PRL-3 is upregulated more than 3-fold in 40.2% of FLT3-ITD
      negative AML patients. PRL-3 expression level is adversely correlated to the
      overall survival of the AML patients, and the AML relapses accompany with re
      upregulation of PRL-3. Mechanistically, aberrant PRL-3 expression promoted cell
      cycle progression and enhanced the antiapoptotic machinery of AML cells to drug
      cytotoxicity through downregulation of p21 and upregulation of Cyclin D1 and CDK2
      and activation of STAT5 and AKT. Depletion of endogenous PRL-3 sensitizes AML
      cells to therapeutic drugs, concomitant with apoptosis by upregulation of cleaved
      PARP (poly ADP ribose polymerase) and apoptosis-related caspases. Xenograft
      assays further confirmed PRL-3's oncogenic role in leukemogenesis. CONCLUSIONS:
      Our results demonstrated that PRL-3 is a novel independent crucial player in both
      FLT3-ITD-positive and FLT3-ITD-negative AML and could be a potential therapeutic
      target.

PMID- 24737399
TI  - New record of the suspected leishmaniasis vector Phlebotomus (Transphlebotomus)
      mascittii Grassi, 1908 (Diptera: Psychodidae: Phlebotominae)--the northernmost
      phlebotomine sandfly occurrence in the Palearctic region.
AB  - Although being typical Mediterranean faunal elements, phlebotomine sandflies have
      also been recorded in central Europe for several countries including Germany,
      where two species, Phlebotomus mascittii and Phlebotomus perniciosus, occur. In
      Europe, P. mascittii is the northernmostly distributed phlebotomine species.
      While P. perniciosus is a proven vector of leishmaniasis as well as various
      sandfly fever causing phleboviruses, the situation for P. mascittii is different.
      For this species, vector competence could not be proven yet, but is strongly
      suspected. During an entomological survey in July 2013, one female sandfly was
      caught in Giessen in the German state of Hesse. Adjacent to the collection site,
      different potential habitats could be found. Morphological examination of the
      cibarium, pharynx, and genitalia revealed the specimen as P. mascittii. This is
      the first reported occurrence for Hesse, and not only the northernmost documented
      occurrence for P. mascittii, but also of the whole subfamily in the Palearctic
      region. New records of proven or suspected vectors are of medical relevance
      because of potential Leishmania and/or Phlebovirus transmission and the awareness
      therefore in the public. 

PMID- 24737400
TI  - The effect of delay in fixation on HER2 expression in invasive carcinoma of the
      breast assessed with immunohistochemistry and in situ hybridisation.
AB  - AIMS: Accurate assessment of HER2 status is essential for selection of patients
      for HER2-targeted treatment such as trastuzumab. This study investigated the
      hypothesis that delayed fixation impairs HER2 assessment. METHODS: 9 carcinomas
      were received fresh, and samples were fixed immediately or put in fixative at
      time intervals up to 24 h. All carcinomas were scored as 3+ with
      immunohistochemistry in properly fixed tissue. RESULTS: 2 of 9 carcinomas (95%
      CIs 6% to 56%) showed reduced immunohistochemical staining with delays in
      fixation of 1 and 8 h. One carcinoma showed low-level amplification with
      fluorescence in situ hybridisation (FISH) when properly fixed and was not
      amplified after delayed fixation. The other carcinomas were amplified at all time
      points. CONCLUSIONS: Delayed fixation impaired HER2 protein expression assessed
      using immunohistochemistry in 22% of 3+ carcinomas. HER2 amplification assessed
      using FISH may be less affected.

PMID- 24737401
TI  - Spinal and supraspinal processing of thermal stimuli: an fMRI study.
AB  - PURPOSE: To assess and characterize responses to innocuous/noxious thermal
      stimuli and heat allodynia using functional spinal magnetic resonance imaging
      (spinal fMRI). MATERIALS AND METHODS: Spinal/supraspinal activation patterns of
      16 healthy subjects were investigated by applying painful and nonpainful heat
      stimuli to dermatome C6 baseline and after sensitization with the heat/capsaicin
      model using fMRI (3T, single-shot TSE, TR 9000 msec, TE 38 msec, FOV 288 * 144 *
      20 mm, matrix 192 * 96, voxel size 1 * 1 * 2 mm). RESULTS: Increased activity was
      observed in ipsi- and contralateral ventral and dorsal spinal horn during noxious
      heat and heat allodynia. During noxious heat, but not during heat allodynia,
      activations were visible in the periaqueductal gray, ipsilateral cuneiform
      nucleus, and ipsilateral dorsolateral pontine tegmentum (DLPT). However, during
      heat allodynia activations were observed in bilateral ruber nuclei, contralateral
      DLPT, and rostral ventromedial medulla oblongata (RVM). Activations in
      contralateral subnucleus reticularis dorsalis (SRD) were visible during both
      noxious heat and heat allodynia (T >2.5, P < 0.01 for all of the above). After
      sensitization, activations in RVM and SRD correlated with activations in the
      ipsilateral dorsal horn of the spinal cord (R = 0.52-0.98, P < 0.05). CONCLUSION:
      Spinal fMRI successfully demonstrates increased spinal activity and secondary
      changes in activation of supraspinal centers involved in pain modulation caused
      by peripheral nociceptor sensitization. J. Magn. Reson. Imaging 2015;41:1046
      1055. (c) 2014 Wiley Periodicals, Inc.

PMID- 24737402
TI  - A phase I/II trial of capecitabine combined with peginterferon alpha-2a in
      Patients with sorafenib-refractory advanced hepatocellular carcinoma.
AB  - BACKGROUND: Several pilot studies have demonstrated the effectiveness of
      combination therapy with pyrimidine fluoride and interferon for advanced
      hepatocellular carcinoma.This study aimed to determine the recommended dose of
      capecitabine combined with peginterferon alpha-2a (Phase I) and evaluate its
      safety and efficacy for sorafenib-refractory advanced hepatocellular carcinoma
      (Phase II). METHODS: Capecitabine was administered daily on days 1-14, while
      peginterferon alpha-2a was administered on days 1, 8, and 15. The cycle was
      repeated every 21 days. The patients were scheduled to receive capecitabine
      [mg/(m(2)?day)] and peginterferon alpha-2a (MUg/week) at 3 dose levels in phase
      I: 1200 and 90 (level 1), 1600 and 90 (level 2), and 2000 and 90 (level 3),
      respectively. RESULTS: A total of 30 patients were enrolled. The recommended dose
      was level 3. Among the 24 patients receiving the drug at the recommended dosage,
      2 (8 %) exhibited a partial response, 9 (38 %) exhibited stable disease, 10 (42
      %) exhibited progressive disease, and 3 (13 %) were not evaluated. The median
      time to progression and overall survival were 3.0 months and 7.2 months,
      respectively. The most common toxicities were decreased white blood cell (88 %),
      neutrophil (88 %), and platelet counts (58 %); fatigue (50 %); and palmar-plantar
      erythrodysesthesia syndrome (42 %). Four patients (17 %) discontinued treatment
      because of severe adverse events. CONCLUSION: Capecitabine at 2000 mg/(m(2)?day)
      combined with peginterferon alpha-2a (90 MUg/week) exhibited moderate, albeit
      manageable, toxicity and was declared as the recommended phase II dose. Further
      research is required to refine the efficacy of this combination.

PMID- 24737403
TI  - Coronary artery perforation after crush technique for stent compression.

PMID- 24737404
TI  - Prevalence and range of GJB2 and SLC26A4 mutations in patients with autosomal
      recessive non-syndromic hearing loss.
AB  - The frequency and distribution of genetic mutations that cause deafness differ
      significantly according to ethnic group and region. Zhejiang is a province in the
      southeast of China, with an exceptional racial composition of the population
      caused by mass migration in ancient China. The purpose of the present study was
      to investigate the prevalence and spectrum of gap junction-beta2 (GJB2), solute
      carrier family 26 (anion exchanger) member 4 (SLC26A4) and GJB3 mutations in
      patients with autosomal recessive non-syndromic hearing loss (ARNHL) in this
      area. A total of 176 unrelated pediatric patients with ARNHL were enrolled in the
      study. A genomic DNA sample was extracted from the peripheral blood. Polymerase
      chain reaction was employed, and the products were sequenced to screen for
      mutations in GJB2. In addition, a SNaPshot sequencing method was utilized to
      detect four hotspot mutations in SLC26A4 (IVS7-2A>G and c.2168A>G) and GJB3
      (c.538C>T and c.547G>A). All patients were subjected to a temporal bone computed
      tomography scan to identify enlarged vestibular aqueducts (EVA). In total, 14
      different mutations, including two new mutations (p.W44L and p.D66N) of GJB2,
      were detected. The most common pathogenic mutation of GJB2 was c.235delC (15.1%),
      followed by c.176_191del16 (1.7%), c.299_300delAT (1.7%), c.508_511dup (0.85%)
      and c.35delG (0.28%) of the total alleles. Mutation analysis of SLC26A4
      demonstrated that 13.6% (24/176) of patients carried at least one mutant allele.
      The patients with EVA (84.2%) had SLC26A4 mutations, and 31% had homozygous
      mutations. Only one patient carried a heterozygous mutation of GJB3 (c.538C>T).
      Compared with the other regions of China, in the present population cohort, the
      prevalence and spectrum of mutations in GJB2 was unique, and in patients with EVA
      the frequency of a homozygous mutation in SLC26A4 was significantly lower. These
      findings may be of benefit in genetic counseling and risk assessment for families
      from this area of China. 

PMID- 24737405
TI  - Institutional differences in carotid artery duplex diagnostic criteria result in
      significant variability in classification of carotid artery stenoses and likely
      lead to disparities in care.
AB  - BACKGROUND: The indications for carotid revascularization are based almost
      exclusively on the results of carotid duplex ultrasonography. Noninvasive
      vascular laboratories show large variation in the diagnostic criteria used to
      classify degree of carotid artery stenosis. We hypothesize that variability of
      these diagnostic criteria causes significant variation in stenosis classification
      directly affecting the number of revascularizations and associated costs. METHODS
      AND RESULTS: The diagnostic criteria to interpret carotid duplex ultrasounds were
      obtained from 10 New England institutions. All carotid duplex scans performed at
      our institution were reviewed from 2008 to 2012. Using the diagnostic criteria
      from each institution, the degree of stenosis that would have been reported was
      classified as 70% to 99% asymptomatic, 80% to 99% asymptomatic, and 50% to 99%
      symptomatic. We then calculated the theoretical number of carotid
      revascularization procedures that this cohort would be offered using each
      institution's diagnostic criteria and the costs of these procedures based on
      reimbursement rates. Among 10 614 patients who underwent 15 534 carotid duplex
      scans, 31 025 arteries were reviewed. Application of the 10 institutions'
      criteria to the patients from our institution yielded marked variation in the
      number classified as 70% to 99% asymptomatic (range, 186-2201), 80% to 99%
      asymptomatic (range, 78-426), and 50% to 99% symptomatic (range, 157-781). If
      revascularizations were based on these results, costs would range from $2.2 to
      $26 million, $0.9 to $5.0 million, and $1.9 to $9.2 million, respectively.
      CONCLUSIONS: Differences in diagnostic criteria to interpret carotid ultrasound
      result in significant variation in classification of carotid artery stenosis,
      likely leading to differences in the number and subsequent costs of
      revascularizations. This theoretical model highlights the need for
      standardization of carotid duplex criteria.

PMID- 24737406
TI  - Efficacy of uvulopalatopharyngoplasty combined with oral appliance in treatment
      of obstructive sleep apnea-hypopnea syndrome.
AB  - OBJECTIVE: This study aimed to investigate the efficacy of UPPP combined with an
      oral appliance (OA) in the treatment of obstructive sleep apnea-hypopnea syndrome
      (OSAHS). METHODS: Forty patients diagnosed with severe OSAHS were randomly
      divided into two groups: 20 patients in the pure surgery group treated by
      uvulopalatopharyngoplasty (UPPP) surgery and the remaining 20 patients in the
      combined treatment group for the combined application of UPPP and OA. Nocturnal
      PSG monitoring was performed in postoperative 0.5 and 3.0a. AHI, SaO2, and sleep
      structure improvement were calculated to compare the treatment efficiency of the
      two groups. RESULTS: The AHI of the combined treatment group in the postoperative
      3 was lower than that of the pure surgery group, whereas the lowest SaO2 value
      was higher than that of the pure surgery group (P < 0.05). The sleep structure
      improvement of the combined treatment group in the postoperative 3a was possibly
      more normal than that of the pure surgery group. CONCLUSION: The long-term
      efficacy of the combined UPPP and OA for the treatment of OSAHS was higher than
      that of pure UPPP treatment.

PMID- 24737407
TI  - Inferior vena cava filter insertion and retrieval patterns in a tertiary referral
      centre in Ireland.
AB  - BACKGROUND: Inferior vena cava (IVC) filters are widely used in clinical practice
      to prevent large, clinically significant pulmonary emboli. Modern filters are
      designed to be retrievable within a specific time window; however, many become
      lost to follow-up. AIM: To examine the insertion and retrieval patterns of IVC
      filters in a tertiary referral teaching hospital in Ireland. METHODS: A
      retrospective review of all IVC filter insertions and retrievals was performed in
      a tertiary referral university teaching hospital which incorporates the national
      referral centre for pelvic and acetabular trauma, over a 22-month period.
      RESULTS: Fifty-seven patients underwent IVC filter insertion with 100% technical
      success. The most common indication was prophylaxis in patients at high risk of
      deep venous thrombosis or pulmonary emboli (64.9%), followed by patients with
      contra-indication to anticoagulation (24.6%) and breakthrough thromboembolic
      events despite anticoagulation (10.5%). IVC filter retrievals were attempted in
      48.9% of patients with a success rate of 86.9%. The mean dwell time for retrieved
      IVC filters was 159.4 days. CONCLUSION: Inferior vena cava filter insertion and
      retrieval patterns in our centre were comparable to trends reported
      internationally with scope for improvement in terms of filter retrieval rates and
      minimising filter dwell time. Particular vigilance is required in younger
      patients where the indication for filter insertion was prophylactic.

PMID- 24737408
TI  - Interferon beta assessment in non-Chinese and Chinese subjects: pharmacokinetics
      and pharmacodynamic activity of an endogenous cytokine are not race dependent.
AB  - Interferon beta-1a (IFNbeta-1a) is a first-line therapy for relapsing multiple
      sclerosis when administered as 30 mcg intramuscularly (IM) once weekly. This
      endogenous cytokine displays pharmacokinetic (PK) attributes consistent with a
      glycoprotein of 20-kDa molecular weight that is administered IM. In this study,
      24 healthy Chinese subjects (11 male, 13 female) each received 4 once-weekly 60
      mcg IM doses of IFNbeta-1a. Serial blood samples were drawn for PK and
      pharmacodynamic (PD) assessments following the first and last dose of drug.
      Results were compared with historical data from a recent PK/PD assessment
      conducted in non-Chinese subjects. Noncompartmental analysis revealed that no
      meaningful differences in either IFNbeta-1a exposure or response were apparent
      between the Chinese and non-Chinese populations. Thus, it was concluded that no
      adjustment in dose regimen is warranted for future assessments of safety and
      efficacy in multiple sclerosis patients of Chinese origin.

PMID- 24737409
TI  - Fabrication of a multifunctional nano-in-micro drug delivery platform by
      microfluidic templated encapsulation of porous silicon in polymer matrix.
AB  - A multifunctional nano-in-micro drug delivery platform is developed by
      conjugating the porous silicon nanoparticles with mucoadhesive polymers and
      subsequent encapsulation into a pH-responsive polymer using microfluidics. The
      multistage platform shows monodisperse size distribution and pH-responsive
      payload release, and the released nanoparticles are mucoadhesive. Moreover, this
      platform is capable of simultaneously loading and releasing multidrugs with
      distinct properties. 

PMID- 24737410
TI  - Thermal methane activation by La(6)O(10)(-) cluster anions.
AB  - The first example of a metal oxide cluster anion, La6 O10 (-) that can activate
      methane under ambient conditions is reported. This reaction is facilitated by the
      oxygen-centered radical (O(-?) ) and follows the hydrogen atom transfer
      mechanism. The La6 O10 (-) has a high vertical electron detachment energy
      (VDE=4.06 eV) and a high symmetry (C4v ). 

PMID- 24737411
TI  - Liquid chromatography-mass spectrometry and chemometric analysis of Ricinus
      communis extracts for cultivar identification.
AB  - INTRODUCTION: Seeds of Ricinus communis contain the toxic protein ricin, a 64 kD
      heterodimeric type II ribosome-inactivating protein that has been used in several
      high-profile poisoning incidents. The ability to determine which cultivar the
      toxin was isolated from via an LC-MS method would be of significant use to law
      enforcement and forensic agencies. OBJECTIVE: To analyse via LC-MS and
      chemometrics (principal components analysis (PCA), orthogonal partial-least
      squares discriminant analysis (OPLS-DA)) extracts of R. communis to identify
      compounds specific to a particular cultivar. METHODS: Seeds from eight specimens
      of six cultivars of R. communis ('carmencita', 'dehradun', 'gibsonii', 'impala',
      'sanguineus' and 'zanzibariensis') were extracted using a standard methodology.
      These extracts were analysed by LC-MS then subjected to chemometric analysis (PCA
      and OPLS-DA). Identified compounds of importance were subjected to high
      resolution Fourier transform (HRFT) MS and MS/MS to elucidate their structures.
      RESULTS: This analysis identified 17 ions as potential cultivar determinators.
      Through accurate mass measurement and MS/MS, molecular formulae for 13 ions were
      determined, including two known and 11 new peptides. CONCLUSION: Unique ions in
      extracts of 'carmencita', 'dehradun', 'gibsonii', 'impala' and 'zanzibariensis'
      were identified that would allow an individual cultivar to be distinguished from
      other cultivars in this study. Although 'sanguineus' extracts contained no unique
      compounds, a unique LC-MS profile would allow for cultivar assignment.

PMID- 24737412
TI  - KLF9, a transcription factor induced in flutamide-caused cell apoptosis, inhibits
      AKT activation and suppresses tumor growth of prostate cancer cells.
AB  - BACKGROUND: Kruppel-like factors (KLFs) are involved in various biological
      processes; emerging studies have indicated that KLF9 plays a critical role in
      regulating tumorigenesis. The role of KLF9 in prostate cancer (PCa), however, has
      not yet been investigated. METHODS: The expression of KLF members, AKT- and
      apoptosis-related proteins were analyzed by Western blot or qRT-PCR. Tet-On
      inducible KLF9 expression was established for the evaluation of the effects of
      KLF9 on cell proliferation, apoptosis, and xenograft tumor growth in nude mice.
      Cell cycle and apoptosis were determined by flow cytometry. RESULTS: KLF9 was
      induced in a time-dependent manner in flutamide-caused apoptosis, and knockdown
      of KLF9 significantly decreased flutamide-induced growth inhibition and apoptosis
      in LNCaP cells. The levels of KLF9 were relatively lower in PCa cell lines,
      particularly in androgen-independent cell lines compared with those in
      nontumorous prostate epithelial cell lines. Overexpression of KLF9 dramatically
      suppressed cell proliferation and caused cell cycle arrest in the G2/M phase and
      cell apoptosis in the androgen-independent cell lines, PC3 and DU145.
      Intriguingly, KLF9 expression severely suppressed the activation of AKT and its
      downstream targets. AKT reactivation partially rescued the KLF9-mediated
      inhibitory effects on the proliferation of PCa cells. More importantly, we found
      that KLF9 overexpression efficiently inhibited the xenograft tumor growth of PCa
      cells. CONCLUSIONS: These data collectively showing that KLF9 substantially
      inhibits AKT activation and abrogates tumor growth of PCa cells, suggest the
      potential of either genetic or pharmacological activation of KLF9 in the
      therapeutic treatment of castration-resistant PCa.

PMID- 24737413
TI  - Ectopic expression of an Arabidopsis dehydration-responsive element-binding
      factor DREB2C improves salt stress tolerance in crucifers.
AB  - KEY MESSAGE: DREB2C acts as a transcriptional activator of the salt tolerance
      related COLD - REGULATED 15A gene. DEHYDRATION-RESPONSIVE ELEMENT BINDING FACTOR
      2C (DREB2C) regulates plant responses to heat stress. We report here that DREB2C
      is induced by NaCl stress in Arabidopsis, based on quantitative RT-PCR analyses
      of transcript levels and DREB2C promoter-controlled GUS activity assays.
      Constitutive overexpression of DREB2C from the cauliflower mosaic virus (CaMV)
      35S promoter led to enhanced salt tolerance in transgenic Arabidopsis and canola
      plants that was characterized by higher chlorophyll content, lower tissue Na(+)
      content, reduced rate of water loss, and tighter membrane integrity in plants
      grown in NaCl-containing medium. Basal expression of the stress-responsive genes
      COLD-REGULATED 15A (COR15A), RESPONSIVE TO DEHYDRATION (RD) 29A and RD29B, was
      higher in transgenic DREB2C-overexpressing Arabidopsis plants than in the wild
      type. Promoter transactivation assays and electrophoretic mobility-shift assays
      showed that DREB2C interacts directly with the three DREs in the COR15A promoter,
      both in vivo and in vitro. Transgenic Arabidopsis constitutively overexpressing
      COR15A from the CaMV35S promoter exhibited greater NaCl tolerance than the
      untransformed wild-type. Taken together, the data suggest that DREB2C functions
      as transcriptional activator that promotes NaCl tolerance, in part through
      upregulation of the stress-responsive gene COR15A.

PMID- 24737414
TI  - Rescue of syringyl lignin and sinapate ester biosynthesis in Arabidopsis thaliana
      by a coniferaldehyde 5-hydroxylase from Eucalyptus globulus.
AB  - KEY MESSAGE: The gene coding for F5H from Eucalyptus globulus was cloned and used
      to transform an f5h -mutant of Arabidopsis thaliana , which was complemented,
      thus verifying the identity of the cloned gene. Coniferaldehyde 5-hydroxylase
      (F5H; EC 1.14.13) is a cytochrome P450-dependent monooxygenase that catalyzes the
      5-hydroxylation step required for the production of syringyl units in lignin
      biosynthesis. The Eucalyptus globulus enzyme was characterized in vitro, and
      results showed that the preferred substrates were coniferaldehyde and coniferyl
      alcohol. Complementation experiments demonstrated that both cDNA and genomic
      constructs derived from F5H from E. globulus under the control of the cinnamate 4
      hydroxylase promoter from Arabidopsis thaliana, or a partial F5H promoter from E.
      globulus, can rescue the inability of the A. thaliana fah1-2 mutant to accumulate
      sinapate esters and syringyl lignin. E. globulus is a species widely used to
      obtain products that require lignin removal, and the results suggest that EglF5H
      is a good candidate for engineering efforts aimed at increasing the lignin
      syringyl unit content, either for kraft pulping or biofuel production.

PMID- 24737416
TI  - Selected papers from the 29th SEGH Conference on Environmental Geochemistry and
      Health. Preface.

PMID- 24737417
TI  - Urinary arsenic levels influenced by abandoned mine tailings in the Southernmost
      Baja California Peninsula, Mexico.
AB  - Gold has been mined at San Antonio-El Triunfo, (Baja California Sur, Mexico)
      since the 18th century. This area has approximately 5,700 inhabitants living in
      the San Juan de Los Planes and El Carrizal hydrographic basins, close to more
      than 100 abandoned mining sites containing tailings contaminated with potentially
      toxic elements such as arsenic. To evaluate the arsenic exposure of humans living
      in the surrounding areas, urinary arsenic species, such as inorganic arsenic
      (iAs) and the metabolites mono-methylated (MMA) and di-methylated arsenic acids
      (DMA), were evaluated in 275 residents (18-84 years of age). Arsenic species in
      urine were analyzed by hydride generation-cryotrapping-atomic absorption
      spectrometry, which excludes the non-toxic forms of arsenic such as those found
      in seafood. Urinary samples contained a total arsenic concentration (sum of
      arsenical species) which ranged from 1.3 to 398.7 ng mL(-1), indicating 33% of
      the inhabitants exceeded the biological exposition index (BEI = 35 ng mL(-1)),
      the permissible limit for occupational exposure. The mean relative urinary
      arsenic species were 9, 11 and 80% for iAs, MMA and DMA, respectively, in the Los
      Planes basin, and 17, 10 and 73%, respectively, in the El Carrizal basin. These
      data indicated that environmental intervention is required to address potential
      health issues in this area.

PMID- 24737415
TI  - Risk factors for gastrointestinal stromal tumor recurrence in patients treated
      with adjuvant imatinib.
AB  - BACKGROUND: Little is known about the factors that predict for gastrointestinal
      stromal tumor (GIST) recurrence in patients treated with adjuvant imatinib.
      METHODS: Risk factors for GIST recurrence were identified, and 2 risk
      stratification scores were developed using the database of the Scandinavian
      Sarcoma Group (SSG) XVIII trial, where 358 patients with high-risk GIST with no
      overt metastases were randomly assigned to adjuvant imatinib 400 mg/day either
      for 12 or 36 months after surgery. The findings were validated in the imatinib
      arm of the American College of Surgeons Oncology Group Z9001 trial, where 359
      patients with GIST were randomized to receive imatinib and 354 were to receive
      placebo for 12 months. RESULTS: Five factors (high tumor mitotic count,
      nongastric location, large size, rupture, and adjuvant imatinib for 12 months)
      were independently associated with unfavorable recurrence-free survival (RFS) in
      a multivariable analysis in the SSGXVIII cohort. A risk score based on these 5
      factors had a concordance index with GIST recurrence of 78.9%. When a simpler
      score consisting of the 2 strongest predictive factors (mitotic count and tumor
      site) was devised, the groups with the lowest, intermediate high, and the highest
      risk had 5-year RFS of 76.7%, 47.5%, and 8.4%, respectively. Both scores were
      strongly associated with RFS in the validation cohort (P < .001 for each
      comparison). CONCLUSIONS: The scores generated were effective in stratifying the
      risk of GIST recurrence in patient populations treated with adjuvant imatinib.
      Patients with nongastric GIST with a high mitotic count are at a particularly
      high risk for recurrence.

PMID- 24737418
TI  - Storm-induced transfer of particulate trace metals to the deep-sea in the Gulf of
      Lion (NW Mediterranean Sea).
AB  - In order to calculate budgets of particulate matter and sediment-bound
      contaminants leaving the continental shelf of the Gulf of Lion (GoL), settling
      particles were collected in March 2011 during a major storm, using sediment
      traps. The collecting devices were deployed in the Cap de Creus submarine canyon,
      which represents the main export route. Particulate matter samples were analyzed
      to obtain mass fluxes and contents in organic carbon, Al, Cr, Co, Ni, Cu, Zn, Cd,
      Pb and La, Nd and Sm. The natural or anthropogenic origin of trace metals was
      assessed using enrichment factors (EFs). Results are that Zn, Cu and Pb appeared
      to be of anthropogenic origin, whereas Ni, Co and Cr appeared to be strictly
      natural. The anthropogenic contribution of all elements (except Cd) was refined
      by acid-leaching (HCl 1 N) techniques, confirming that Zn, Cu and Pb are the
      elements that are the most enriched. However, although those elements are highly
      labile (59-77%), they do not reflect severe enrichment (EFs <4). Most particles
      originate from the Rhone River. This has been confirmed by two different tracing
      procedures using rare earth elements ratios and concentrations of acid-leaching
      residual trace metals. Our results hence indicate that even in this western
      extremity of the GoL, storm events mainly export Rhone-derived particles via the
      Cap de Creus submarine canyons to the deep-sea environments. This export of
      material is significant as it represents about a third of the annual PTM input
      from the Rhone River.

PMID- 24737419
TI  - Geochemical evolution of groundwater salinity at basin scale: a case study from
      Datong basin, Northern China.
AB  - A hydrogeochemical investigation using integrated methods of stable isotopes
      ((18)O, (2)H), (87)Sr/(86)Sr ratios, Cl/Br ratios, chloride-mass balance, mass
      balance and hydrogeochemical modeling was conducted to interpret the geochemical
      evolution of groundwater salinity in Datong basin, northern China. The delta(2)H,
      delta(18)O ratios in precipitation exhibited a local meteoric water line of
      delta(2)H = 6.4 delta(18)O -5 (R(2) = 0.94), while those in groundwater suggested
      their meteoric origin in a historically colder climatic regime with a speculated
      recharge rate of less than 20.5 mm overall per year, in addition to recharge from
      a component of deep residual ancient lake water enriched with Br. According to
      the Sr isotope binary mixing model, the mixing of recharges from the Shentou
      karst springs (24%), the western margins (11%) and the eastern margins (65%)
      accounts for the groundwater from the deep aquifers of the down-gradient parts in
      the central basin is a possible mixing mechanism. In Datong, hydrolysis of
      silicate minerals is the most important hydrogeochemical process responsible for
      groundwater chemistry, in addition to dissolution of carbonate and evaporites. In
      the recharge areas, silicate chemical weathering is typically at the
      bisiallitization stage, while that in the central basin is mostly at the
      monosiallitization stage with limited evidence of being in equilibrium with
      gibbsite. Na exchange with bound Ca, Mg prevails at basin scale, and intensifies
      with groundwater salinity, while Ca, Mg exchange with bound Na locally occurs in
      the east pluvial and alluvial plains. Although groundwater salinity increases
      with the progress of water-rock/sediment interactions along the flow path, as a
      result of carbonate solubility control and continuous evapotranspiration, Na-HCO3
      and Na-Cl-SO4 types of water are usually characterized respectively in the deep
      and the shallow aquifers of an inland basin with a silicate terrain in an arid
      climatic regime. 

PMID- 24737420
TI  - Nonenhanced arterial spin labeled carotid MR angiography using three-dimensional
      radial balanced steady-state free precession imaging.
AB  - PURPOSE: To optimize and preliminarily evaluate a three-dimensional (3D) radial
      balanced steady-state free precession (bSSFP) arterial spin labeled (ASL)
      sequence for nonenhanced MR angiography (MRA) of the extracranial carotid
      arteries. MATERIALS AND METHODS: The carotid arteries of 13 healthy subjects and
      2 patients were imaged on a 1.5 Tesla MRI system using an undersampled 3D radial
      bSSFP sequence providing a scan time of ~4 min and 1 mm(3) isotropic resolution.
      A hybridized scheme that combined pseudocontinuous and pulsed ASL was used to
      maximize arterial coverage. The impact of a post label delay period, the sequence
      repetition time, and radiofrequency (RF) energy configuration of pseudocontinuous
      labeling on the display of the carotid arteries was assessed with contrast-to
      noise ratio (CNR) measurements. Faster, higher undersampled 2 and 1 min scans
      were tested. RESULTS: Using hybridized ASL MRA and a 3D radial bSSFP trajectory,
      arterial CNR was maximized with a post label delay of 0.2 s, repetition times >=
      2.5 s (P < 0.05), and by eliminating RF energy during the pseudocontinuous
      control phase (P < 0.001). With higher levels of undersampling, the carotid
      arteries were displayed in <= 2 min. CONCLUSION: Nonenhanced MRA using hybridized
      ASL with a 3D radial bSSFP trajectory can display long lengths of the carotid
      arteries with 1 mm(3) isotropic resolution.

PMID- 24737421
TI  - Rearrangement structure-independent strategy of CNV breakpoint analysis.
AB  - Rare copy number variations (CNVs) generated by human genomic rearrangements have
      been shown to play an important role in pathogenesis of human diseases and
      cancers. CNV breakpoint analysis can help define genomic location, genetic
      content and sequence structure of pathogenic CNVs. This process is vital to
      elucidate CNV mutational mechanism and etiology of CNV-associated disorders.
      However, it is technically challenging to map CNV breakpoints at base-pair level,
      especially in the genomic regions with sequence complexity. In this study, we
      developed a new method of capture and breakpoint approaching sequencing (CBAS) to
      efficiently obtain CNV breakpoint sequences. This strategy is independent of CNV
      structures and applicable to various CNV types. As was demonstrated in CNV
      associated patients with neurological disorders, CBAS achieved fine mapping of
      breakpoint sequences for compound deletion, complex duplication, and
      translocation. Intriguingly, CBAS also revealed unexpected CNV complexity
      involving long-range DNA rearrangement. Our observations showed that CBAS is an
      efficient method for obtaining CNV breakpoint sequence and mapping insertional
      events as well. This method can facilitate the researches on CNV-associated human
      diseases and cancers. CBAS is also applicable to mapping the integration sites of
      retrovirus (such as HIV) and transgenes in model organisms. 

PMID- 24737422
TI  - Discrimination of common bean cultivars using multiplexed microsatellite markers.
AB  - Analysis of DNA polymorphisms allows for the genetic identification and precise
      discrimination of species with a narrow genetic base such as common bean. The
      primary objectives of the present study were to molecularly characterize
      commercial common bean varieties developed at various research institutions using
      microsatellite markers and to determine the degree of genetic diversity among the
      bean varieties analyzed. Fifty cultivars representing 12 grain classes and 64
      genitors, i.e., accessions used to develop these cultivars, were characterized.
      Based on an analysis of 24 simple sequence repeats, the estimates for the average
      number of alleles and genetic diversity were 8.29 and 0.646, respectively. The
      combined probability of identity was estimated at 7.05 x 10(-17), indicating a
      high individual discriminatory power. Thirty-two percent of the cultivars
      exhibited heterogeneity for multiple loci that reflected either homozygosity for
      different alleles of a given locus in different individuals or heterozygosity for
      the locus. The average genetic diversity for the groups of cultivars and genitors
      was 0.605 and 0.660, respectively, with no genetic differentiation (FST) between
      these groups. Although similar estimates of expected heterozygosity were observed
      when the cultivars were grouped by release date, a greater number of private
      alleles was observed in the most recent cultivars. The genetic differentiation
      among cultivars originating from different institutions was not different from
      zero (FST = 0.01). The molecular profile database derived from these analyses may
      increase the statistical power of genetic estimates and may be incorporated into
      breeding programs for common bean. Furthermore, the profiles obtained for the
      different cultivars may be used as molecular descriptors to complement
      traditional descriptors used in distinctiveness, uniformity and stability tests,
      thereby improving the traceability of samples and their derivatives and helping
      to protect the intellectual property rights of breeders. 

PMID- 24737423
TI  - Positions of pluripotency genes and hepatocyte-specific genes in the nucleus
      before and after mouse ES cell differentiation.
AB  - Spatial positioning of genes in the cell nucleus plays an important role in the
      regulation of genomic functions. Evidence for changes in gene positioning
      associated with transcriptional activity has been reported. However, our
      understanding of this phenomenon is still quite limited. We examined how
      pluripotency genes and hepatocyte-specific genes behave during the
      differentiation of mouse embryonic stem (ES) cells into hepatocytes, by targeting
      the loci of the Klf4, Nanog, Oct4, Sox2, Cyp7alpha1, Pck1, Tat, and Tdo2 genes,
      and using three-dimensional fluorescence in situ hybridization analyses. We found
      that each gene has a distinctly inherent localization profile in the ES cell
      nucleus. During differentiation, the Klf4, Nanog, Oct4, Cyp7alpha1, Pck1, and Tat
      loci shifted toward the nuclear center, while the Sox2 and Tdo2 loci shifted
      toward the periphery. The Klf4, Nanog, Oct4, and Tdo2 seem to prefer the outer
      regions, rather than the inner regions, when they are active. We also found that
      the radial positioning of the focused genes in the hepatocyte cell nucleus was
      highly correlated with the local GC content and the gene density of the
      surrounding region, but not with gene activity.

PMID- 24737424
TI  - Microsatellite markers derived from Japanese scallop (Mizuhopecten yessoensis)
      expressed sequence tags.
AB  - Japanese scallop (Mizuhopecten yessoensis) is a cold-water shellfish, and a
      species of economic importance in China. In this study, we developed and
      evaluated simple sequence repeat (SSR) markers from the expressed sequence tags
      (ESTs) of M. yessoensis. The characteristics of 12 EST-SSR loci were investigated
      in 30 individual scallops, and the result revealed that the number of alleles per
      locus ranged from 2-4, with an observed heterozygosity ranging from 0.0333
      0.7692, and an expected heterozygosity ranging from 0.0333-0.6312. Only two loci
      were found to depart significantly from the Hardy-Weinberg equilibrium (P <
      0.05). The result of our study suggested that these markers could be considered
      as potential markers for studying the population structure of M. yessoensis and
      its intraspecific variation.

PMID- 24737425
TI  - Overexpression of the growth arrest-specific homeobox gene Gax inhibits
      proliferation, migration, cell cycle progression, and apoptosis in serum-induced
      vascular smooth muscle cells.
AB  - The Gax gene has been implicated in a variety of cell-developmental and
      biological processes, and aberrant Gax expression is linked to many diseases. In
      this study, to provide important insights for Gax-based gene therapy in vein
      graft restenosis and its anti-restenotic mechanism, we used rabbit vascular
      smooth muscle cells (VSMCs) to investigate the effects of Gax overexpression on
      proliferation, migration, cell cycle, and apoptosis in a serum-stimulated
      culture. Rabbit VSMC lines that stably overexpressed Gax were established by
      transfection with recombinant adenoviral vector Ad5-Gax. The effect of Gax
      overexpression on in vitro serum-induced VSMCs proliferation, migration, cell
      cycle, and apoptosis was assessed by MTT, wound healing, and flow cytometry
      assays, respectively. To investigate the effect of Gax overexpression on PCNA and
      MMP-2 in serum-induced VSMCs, immunocytochemistry, RT-PCR, and gelatin zymography
      were performed. The results clearly showed that Gax overexpression decreases PCNA
      expression in serum-induced VSMCs. Gax overexpression also significantly
      inhibited cell proliferation by blocking entry into the S-phase of the cell
      cycle, promoted cell apoptosis, and reduced cell migration activity by
      downregulating MMP-2 release and activity. These findings indicate that Gax would
      be an optimal target gene for gene therapy to treat vein graft restenosis.

PMID- 24737426
TI  - Prediction of disease-related microRNAs by incorporating functional similarity
      and common association information.
AB  - The identification of human disease-related microRNAs (miRNAs) is important for
      understanding the pathogenesis of diseases, but to do this experimentally is a
      costly and time-consuming process. Computational prediction of disease-related
      miRNA candidates is a valuable complement to experimental studies. It is
      essential to develop an effective prediction method to provide reliable
      candidates for subsequent biological experiments. In this study, we constructed a
      miRNA functional similarity network based on calculation of the functional
      similarity between each pair of miRNAs. Here, we present a new method (DismiPred)
      for predicting disease-related miRNA candidates based on the network. This method
      incorporates functional similarity and common association information to achieve
      an efficient prediction performance. DismiPred has been successfully shown to
      recover experimentally validated disease-related miRNAs for 12 common human
      diseases, with an F-measure ranging from 69.49 to 91.69%. Furthermore, a case
      study examining breast neoplasms showed that DismiPred could uncover novel
      disease-related miRNAs. DismiPred is useful for further experimental studies on
      the involvement of miRNAs in the pathogenesis of diseases. 

PMID- 24737427
TI  - Significance of SODD expression in childhood acute lymphoblastic leukemia and its
      influence on chemotherapy.
AB  - This study explored the clinical significance of silencer of death domain (SODD)
      expression in childhood acute lymphoblastic leukemia (ALL) and its influence on
      chemotherapy as well as the effect of SODD expression on apoptosis of leukemic
      cells. The expression of SODD proteins in different ALL groups was determined by
      immunocytochemistry. The SODD RNAi-interfering plasmid was constructed and
      transferred to Jurkat cells, and the effects of SODD expression on cell
      proliferation and apoptosis were analyzed using the MTT and FCM methods. The
      expressions of SODD, Phospho-NF-kappaB-P65, Bcl-2, and Caspase 3 were detected by
      Western blot analysis. The expression of SODD proteins was significantly higher
      in the ALL groups than in the control group (P < 0.05). The positive expression
      rate of SODD was significantly higher in refractory/relapsed and clinical high
      risk groups than in standard-risk, initial treatment, and complete remission
      groups (P < 0.05). Microtubule-targeting drugs such as vincristine and taxol can
      notably down-regulate SODD expression during apoptosis, whereas DNR, and Ara-c
      cannot. The sensitivity of Jurkat cells to chemotherapeutic drugs increased with
      down-regulated SODD expression induced by SODD-interfering plasmid transfection.
      The sensitivity of the cells transfected with SODD-cloning genes decreased. SODD
      expression was high in the ALL children. These findings indicated that SODD over
      expression might be correlated with the clinical classification, curative effect,
      and prognosis of ALL cells. Microtubule-targeting drugs can specifically down
      regulate SODD expression in leukemic cells, thereby increasing the sensitivity of
      leukemic cells to SODD-targeting chemotherapeutics. In contrast, increased SODD
      expression tends to reduce sensitivity.

PMID- 24737428
TI  - Analysis of intervertebral disc-related genes.
AB  - Intervertebral disk disease is a common clinical disorder manifested by pain,
      ataxia, paresis, motor paralysis, and sensorimotor paralysis. The clinical
      features, diagnosis, and treatment of cervical and thoracolumbar disk disease
      have been unclear until now. In this study, some differentially expressed genes
      were identified, and a network was constructed based on these genes. Through the
      statistical analysis of nodes and the contrast of 2 more connectivity nodes, it
      was found that the nodes in the network are in an important position and play key
      roles. Several of these genes, including MAP2K6, MAP2K3, and MAPK14, belong to
      the MAP kinase family, and several genes, including RHOBTB2, RHOQ, and RHOH,
      belong to the RHO family. Therefore, we hypothesize that the development of
      intervertebral disk disease is related to MAP and RHO family proteins.

PMID- 24737429
TI  - Effects of curcumin on hippocampal expression of NgR and axonal regeneration in
      Abeta-induced cognitive disorder rats.
AB  - Curcumin has been widely used for the prevention and treatment of Alzheimer's
      disease (AD), but its mechanism is still not clear. Inhibitory factors of axonal
      regeneration have been shown to cause a series of pathophysiological changes in
      the early period of AD. In this study, the co-receptor (Nogo receptor; NgR) of
      three axonal growth-inhibitory proteins was examined, and effects of curcumin on
      spatial learning and memory abilities and hippocampal axonal growth were
      investigated in amyloid beta-protein (Abeta)1-40-induced AD rats. Results showed
      that the expression of NgR in the AD group significantly increased and the number
      of axonal protein-positive fibers significantly reduced. The spatial learning and
      memory abilities of AD rats were significantly improved in the curcumin group.
      Furthermore, hippocampal expressions of NgR mRNA and protein decreased, and the
      expression of axonal protein significantly increased. There was a negative
      correlation between the expression of NgR and axonal growth. Together, these
      results suggested that curcumin could improve the spatial learning and memory
      abilities of AD rats. The mechanism might be related with its lowering of
      hippocampal NgR expression and promoting axonal regeneration. 

PMID- 24737430
TI  - Evaluation of the biodegradability of petroleum in microcosm systems by using
      mangrove sediments from Camamu Bay, Bahia, Brazil.
AB  - We investigated the biodegradability of oil in mangrove sediment from Camamu Bay
      and measured its effect on the bacterial community. Microcosms of mangrove
      sediment were contaminated with 0.1, 0.5, 1, 2, and 5% (w/v) oil, and the
      microbial activity was compared to that in uncontaminated sediment. The evolution
      of CO2 and gas chromatography showed the mineralization of oil compounds, which
      could reach 100%. Bacterial diversity was determined by polymerase chain reaction
      using a set of primers for the V3 and V6-V8 regions of 16S rDNA. The band profile
      obtained by denaturing gradient gel electrophoresis of the amplicons that were
      obtained for the V3 region showed a negative correlation between band number and
      oil concentration, whereas that of the V6-V8 region showed a positive correlation
      between band numbers and oil concentration. The latter also gave similar results
      for microcosms that were contaminated with 2 and 5% oil. These results
      demonstrate the mangrove sediment's capacity to recover from oil contamination
      (in vitro) and suggest that native mangrove microorganisms contain enzymes
      necessary for the catabolism of oil. 

PMID- 24737431
TI  - Aberrant DNA methylation of the P16, MGMT, and hMLH1 genes in combination with
      the methylenetetrahydrofolate reductase C677T genetic polymorphism and folate
      intake in gastric cancer.
AB  - Epidemiological studies have indicated that folate metabolism is correlated with
      increased risk of gastric cancer. Since methylenetetrahydrofolate reductase
      (MTHFR) is an important enzyme involved in folate metabolism, in this study, we
      examined whether polymorphisms and haplotypes of MTHFR are correlated with the
      risk of gastric cancer. The polymorphisms MTHFR C677T and MTHFR A1298C were
      genotyped by polymerase chain reaction (PCR)-restriction fragment length
      polymorphism (RFLP) analysis in 285 patients and 570 healthy controls.
      Association analyses based on binary logistic regression were conducted to
      determine the odds ratio (OR) and its 95% confidence interval (95%CI) for each
      genotype. The MTHFR 677TT genotype was significantly related with a reduced risk
      of gastric cancer (OR = 0.60, 95%CI = 0.39-0.92) compared to the CC genotype.
      Similarly, the MTHFR 1298CC genotype was significantly associated with a
      decreased risk of cancer (OR = 0.52, 95%CI = 0.32- 0.81). Haplotype analysis
      showed that the TC haplotype was associated with a reduced risk of gastric cancer
      compared to the most common haplotype, CA (OR = 0.28, 95%CI = 0.12-0.60). Our
      results suggest that the MTHFR C677T and MTHFR A1298C polymorphisms are related
      to gastric cancer susceptibility in the Chinese population. 

PMID- 24737432
TI  - Karyotypic diversity in a population of Bryconamericus aff. iheringii
      (Characidae).
AB  - Bryconamericus comprises 56 species distributed into three groups, on the basis
      of the position and shape of the maxillary teeth: B. exodon, B. microcephalus and
      B. iheringii groups. Few cytogenetic data are available for this genus, but the
      diploid number of 52 chromosomes is quite common, although the karyotypic
      variability is extensive. This study aimed to characterize a population of B.
      aff. iheringii and thus contribute more cytogenetic information and better
      understanding of the structure and karyotypic evolution of this genus. We found 6
      cytotypes with different NOR patterns: cytotype I showed a karyotype formula of
      12m+10sm+16st+14a (FN = 90) and single NORs; cytotype II with 18m+14sm+10st+10a
      (FN = 94) and cytotype III with 20m+18sm+4st+10a (FN = 94), showing both single
      and multiple NORs; cytotype IV with 20m+14sm+12st+6a (NF = 98), cytotype V with
      22m+18sm+8st+4a (FN = 100) and cytotype VI with 18m+24sm+6st+4a (FN = 100), all
      with multiple NORs. Cytotype I is the most different in relation to FN and NOR
      pattern, and can be regarded as belonging to another species of the genus
      Bryconamericus, living in sympatry in Tres Bocas Stream. The remaining cytotypes
      may have been generated by crosses between them and by pericentric inversions.
      Meiotic cells were also analyzed and showed that despite the high karyotypic
      variability, chromosome pairing occurred normally. The great variability found in
      B. aff. iheringii may be related to a high degree of polymorphism; nevertheless,
      the possibility of occurrence of more than one species in this location is not
      ruled out, demonstrating the need for conservation of the Tres Bocas Stream.

PMID- 24737433
TI  - Identification and characterization of differentially expressed genes during
      incompatible interaction between the foliar rust Melampsora larici-populina and
      poplar.
AB  - Poplars are extensively cultivated worldwide, and their susceptibility to the
      foliar rust fungus leads to considerable damages in plantations. To better
      understand the molecular basis of poplar responses to the foliar rust,
      suppression subtractive hybridization was used to identify the potential
      important or novel genes involved in the Populus szechuanica infection by
      Melampsora larici-populina. A total of 515 expressed sequence tags (ESTs) with
      high quality were obtained and clustered into 66 contigs and 75 singletons to
      give a set of 141 uniESTs. The nucleotide Basic Local Alignment Search Tool
      (BLASTn) program was used to search for homologous sequences of the uniESTs in
      the GenBank database. Among them, 92.9% showed homology to the poplar genome, and
      2% showed similarity to the rust fungus genome. In addition, homology to known
      genes was analyzed by the BLASTx algorithm, and approximately 50% of the uniESTs
      were significantly homologous to genes encoding proteins with known functions.
      Based on a reverse transcription-polymerase chain reaction (PCR) and quantitative
      PCR approach, five uniESTs were analyzed, and the results showed that the
      expression level of the thaumatin-like gene was highest at 72 h post-inoculation,
      and the pathogenesis-related protein 1 gene was highest at 48 h post-inoculation.
      The information generated in this study provides new clues to aid in the
      understanding of incompatibility between poplar and the foliar rust. 

PMID- 24737434
TI  - A genetic linkage study in Brazil identifies a new locus for persistent
      developmental stuttering on chromosome 10.
AB  - Although twin, adoption, and family studies demonstrate that genetic factors are
      involved in the origins of stuttering, the mode of transmission of the disorder
      in families is not well defined and stuttering is considered a genetically
      complex trait. We performed a genome-wide linkage scan in a group of 43 Brazilian
      families, each containing multiple cases of persistent developmental stuttering.
      Linkage analysis under a dominant model of inheritance generated significant
      evidence of linkage in two Brazilian families, with a combined maximum single
      point LOD score of 4.02 and a multipoint LOD score of 4.28 on chromosome 10q21.
      This demonstrated the presence of a novel variant gene at this locus that
      predisposes individuals to stuttering, which provides an opportunity to identify
      novel genetic mechanisms that underlie this disorder. 

PMID- 24737435
TI  - Mutation screening of TSC1 and TSC2 genes in Chinese Han children with tuberous
      sclerosis complex.
AB  - Tuberous sclerosis complex (TSC) is an autosomal dominant neurogenetic disorder
      caused by mutations in the TSC1 or TSC2 genes and is frequently associated with
      hamartoma formation in multiple organ systems. Here, we report two novel
      mutations in the TSC2 gene, including a splicing mutation (IVS 29 +1G>C) in
      intron 29 and a deletion/insertion mutation (C.5090-5092delCCA- inAG) in exon 39
      in two Chinese Han children with TSC whose first clinical manifestation was
      seizure. The identification of these two mutations confirmed the diagnosis of TSC
      and expands the spectrum of TSC2 mutations causing TSC.

PMID- 24737436
TI  - Prediction and extraction of microRNA2target interactions associated with
      leukemia.
AB  - MicroRNAs are small, non-coding RNAs that regulate gene expression by suppressing
      mRNA translation or inducing mRNA degradation, and have been implicated in a
      growing number of diseases. To understand microRNAs' function, it is vital to
      identify microRNA2target interactions. This work explores the prediction and
      extraction of leukemia-associated microRNA2target interactions, based on text
      mining. We extracted 371 interactions of microRNA2targets that, from prior
      knowledge, could be related to leukemia. By measuring similarities between
      unknown and known targets, the study could also predict some interactions of
      microRNA2targets. To analyze the prioritized data, the proposed approach
      identified some microRNA2target interactions, 17 of which were validated by other
      evidences. The remaining unconfirmed interactions provide a resource for leukemia
      researchers. Experimental results show the work has promise for predicting and
      extracting interactions of microRNA2targets related to leukemia.

PMID- 24737437
TI  - Polymorphisms in the delta-like 2 homolog gene and their association with growth
      and meat-quality traits in Qinchuan cattle.
AB  - The delta-like 2 homolog (DLK2) modulates adipogenesis, hematopoiesis,
      osteogenesis, and other cell-differentiation processes. In the present study, we
      detected potential polymorphisms in the DLK2 gene in 604 individuals of Qinchuan
      cattle by using PCR-RFLP and DNA-sequencing methods. Herein, we identified five
      novel single-nucleotide polymorphisms (SNPs) (g.888G>A, g.910A>G, g.995G>A,
      g.4321A>G, g.4850A>G) and analyzed their association with measured traits. Four
      of the five analyzed polymorphisms were associated with at least one of the
      following traits: body weight (BW), chest depth (CD), chest circumference (CC),
      back fat thickness (BT), and rib-eye area (REA). To the best of our knowledge,
      our research is the first to report the association of DLK2 gene polymorphisms
      with growth and meat quality traits in Qinchuan cattle. In summary, the results
      of our study suggest that the DLK2 gene can be used as a candidate gene in beef
      cattle breeding. 

PMID- 24737438
TI  - Relationship between the cholesterol ester transfer protein TaqIB polymorphism
      and the lipid-lowering effect of atorvastatin in patients with coronary
      atherosclerotic heart disease.
AB  - This study aimed to investigate the relationship between the cholesterol ester
      transfer protein (CETP) gene TaqIB polymorphism and the lipid-lowering effect of
      atorvastatin in patients with coronary atherosclerotic heart disease. Two hundred
      eighty-eight patients were divided into a control group, an acute coronary
      syndrome (ACS) group, and a stable coronary heart disease (CHD) group. Blood
      biochemical indices were determined using the enzyme method, and polymerase chain
      reaction-restriction fragment length polymorphism (PCR-RFLP) analysis was
      performed to study the TaqIB polymorphism of the CETP gene. The ACS and stable
      CHD groups were treated with atorvastatin, and blood lipid levels were reexamined
      after three months. Plasma levels of total cholesterol (TC), low-density
      lipoprotein cholesterol (LDL-C), and lipoprotein(a) were all significantly higher
      in the ACS and stable CHD groups compared to the control group (P < 0.05 or P <
      0.01). After three months of treatment with atorvastatin, plasma levels of TC,
      LDL-C, triglycerides (TG) (only in patients with genotype B2B2), and
      lipoprotein(a) (only in patients with genotype B1B2) were all significantly
      decreased (P < 0.05 or P < 0.01). After treatment, the plasma level of TG was
      lower in patients with genotype B2B2 compared to patients with genotypes B1B1 or
      B1B2 (B1 carriers) (P < 0.01). Therefore, the CETP TaqIB polymorphism is
      associated with the lipid-lowering effect of atorvastatin in patients with CHD.

PMID- 24737439
TI  - Genetic characterization of Curraleiro Pe-Duro bovine breed from a conservation
      herd of Brazilian semiarid.
AB  - Curraleiro Pe-Duro is a rustic bovine taurine breed found in Northeast of Brazil;
      this breed has decreased its production potentially in order to adapt to the
      region environment conditions. Consequently, it is under risk of extinction and
      is maintained at a preservation center in Piaui State, Brazil, as a source of
      genetic material adapted to local conditions. We analyzed genetic variability of
      this breed using microsatellite markers. Sixty animals were genotyped using 11
      microsatellite loci normally used for paternity tests in bovines. The observed
      number of alleles ranged from 5 to 9, and the effective number of alleles ranged
      from 2.01 to 4.64. The Shannon index ranged from 0.949 to 1.669. The expected
      heterozygosity ranged from 0.510 to 0.798. Polymorphism information content
      values ranged from 0.453 to 0.751. Divergence from Hardy-Weinberg equilibrium was
      significant and the mean FIS value was 0.010. We conclude that this breed still
      has some genetic diversity, but with evident risk due to genetic drift caused by
      current breeding management. It will be necessary to insert animals from other
      herds to obtain the desired level of genetic variability in this breed remnant. 

PMID- 24737440
TI  - A new high-frequency allele of the BM2113 locus in the Yunnan mithun population.
AB  - The BM2113 locus was amplified in Yunnan mithun (Bos frontalis) from the
      southwest mountains of China. It showed a high degree of polymorphism with a
      total of 12 alleles. The 121-bp polymorphic allele of the BM2113 locus that
      accounted for 37.1% of homozygotes was the predominant allele with a frequency of
      58.57%, identified as mithun-specific for Bos species in Yunnan mithun. The
      polymorphism information content value was high with a mean of 0.6170, the
      expected and observed heterozygosity was moderate with values of 0.6427 and
      0.6000, respectively, and the BM2113 locus was under Hardy-Weinberg equilibrium
      (P = 0.2897) in the Yunnan mithun population. This study elucidated the genetic
      diversity, multi-origin, specific alleles, and characterization of mithun. 

PMID- 24737442
TI  - Estimated radiation risk of cancer from medical imaging in haemodialysis
      patients.
AB  - BACKGROUND: In recent years the widespread use of medical procedures increased
      the cumulative effective doses of ionizing radiation. Although many haemodialysis
      patients undergo multiple examinations with high radiation exposure, no data are
      available characterizing their attendant potential risks of cancer. METHODS: The
      radiation exposures were obtained from a retrospective study of 159 consecutive
      haemodialysis patients with a follow-up duration >= 1 year. Effective dose and
      organ dose were estimated on an individual basis. Radiation risk was expressed as
      risk of exposure-induced death (REID) (%). RESULTS: The 159 patients (101 males)
      were followed for a median of 2.7 years (mean 3.0 years). A total of 486 patient
      years were available for follow-up. The mean age at study entry was 65.3 years.
      The mean cumulative organ doses were 103, 102, 100, 99, 77 and 58 mSv for
      kidneys, lung, stomach, liver, colon and bone marrow, respectively. On average,
      computed tomography, nuclear medicine and interventional radiology accounted for
      90, 4.5 and 5.5% of organ doses, respectively. The average REID was 0.99% (i.e.
      odds 1 in 100) and the median REID was 0.45%. At univariate analysis, increasing
      age and presence of diabetes were independent predictors of lower REID, whilst
      patients eligible for kidney transplantation were exposed to a significantly
      higher REID. At multivariate analysis, younger age was an independent predictor
      of higher REID. CONCLUSIONS: The excess cancer risk-attributable radiation
      exposure in haemodialysis patients is not negligible. Particular attention should
      be paid to younger patients and to patients who will undergo kidney
      transplantation.

PMID- 24737441
TI  - Protein kinase cAMP-dependent regulatory type II beta (PRKAR2B) gene variants in
      antipsychotic-induced weight gain.
AB  - OBJECTIVE: Antipsychotics are effective in treating schizophrenia symptoms.
      However, the use of clozapine and olanzapine in particular are associated with
      significant weight gain. Mouse and human studies suggest that the protein kinase
      cAMP-dependent regulatory type II beta (PRKAR2B) gene may be involved in energy
      metabolism, and there is evidence that it is associated with clozapine's effects
      on triglyceride levels. We aimed at assessing PRKAR2B's role in antipsychotic
      induced weight gain in schizophrenia patients. METHODS: DNA samples from adult
      schizophrenia or schizoaffective disorder patients of mixed ancestry were
      genotyped, and weight gain was assessed. We analyzed 16 tag single-nucleotide
      polymorphisms across the PRKAR2B gene in a Caucasian subset treated either with
      clozapine or olanzapine (N = 99). Linear regression based on an additive model
      was performed with the inclusion of relevant covariates. RESULTS: Normalized per
      cent weight change was analyzed, revealing that patients with the minor allele at
      rs9656135 had a mean weight increase of 4.1%, whereas patients without this
      allele had an increase of 3.4%. This association is not significant after
      correcting for multiple testing. CONCLUSIONS: Because of limited power, PRKAR2B's
      role in antipsychotic-induced weight gain is unclear, but biological evidence
      suggests that PRKAR2B may be involved. Further research in larger sample sizes is
      warranted.

PMID- 24737443
TI  - Towards the revival of alkaline phosphatase for the management of bone disease,
      mortality and hip fractures.

PMID- 24737444
TI  - Epidemiology of patients in England and Wales with autosomal dominant polycystic
      kidney disease and end-stage renal failure.
AB  - BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is the leading
      genetic cause of end-stage renal failure (ESRF). The epidemiology of the incident
      ADPKD patient cohort requiring renal replacement therapy (RRT) in England and
      Wales has not been described. METHODS: We used a retrospective cohort design.
      Incident adult patients commencing RRT between 1 January 2000 and 31 December
      2011 in England and Wales were identified from the UK Renal Registry. Patients
      were stratified into three groups based on primary renal diagnosis (PRD): (i)
      ADPKD, (ii) diabetes as PRD, (iii) individuals with another PRD ('other').
      Baseline demographics, comorbidity, care-related measures and outcomes including
      patient survival are described. RESULTS: A total of 52,608 individuals started
      RRT during the study period, 3598 (6.8%) had ADPKD, 12,137 (23.1%) diabetes as
      PRD and 36,873 had another PRD diagnosis. The median age of commencing RRT was 55
      years in the ADPKD group compared with 62 and 66 years in those with diabetes or
      'other' PRD, respectively. The median age of starting RRT did not change within
      the ADPKD group over the 10-year period. Median age at death was similar across
      all groups. The ADPKD group had a lower hazard for all-cause mortality compared
      with the 'other' PRD group (adjusted hazard ratio 0.45, 95% CI 0.38-0.53). In all
      PRD groups, crude mortality rates had improved between 2000-06 and 2007-11.
      CONCLUSION: Although engaged in renal services earlier than some other patient
      groups, individuals with ADPKD start RRT at a younger age and this has remained
      unchanged over the last decade. Developing a nationwide cohort and an enhanced
      disease-specific dataset would facilitate a wide range of research and quality
      improvement initiatives to try to modify progression to ESRF and the course of
      RRT.

PMID- 24737445
TI  - Estrogen is a novel regulator of Tnfaip1 in mouse hippocampus.
AB  - Tumor necrosis factor-induced protein 1 (Tnfaip1), also known as B12, has been
      previously identified as a tumor necrosis factor-alpha (TNF-alpha)-inducible
      protein and is involved in the cytokinesis signaling pathway, DNA synthesis,
      innate immunity, cell apoptosis, Alzheimer's disease (AD) and type 2 diabetic
      nephropathy. However, little is known regarding the expression of Tnfaip1 in
      various tissues or its accurate role in these physiological functions. The focus
      of this study was on Tnfaip1 expression in different tissues, with a high
      expression in mouse hippocampus being identified. The age- and gender-related
      expression of Tnfaip1 in hippocampus was also investigated. The distribution of
      Tnfaip1 was mapped using fluorescent immunostaining. Although immunoactivity was
      found in the CA1, CA3 and DG subregions of the hippocampus in E17.5 and P6 mice,
      strong staining was only detected in the CA3 subregion in adult mice. These data
      suggested that Tnfaip1 expression in hippocampus may be regulated by estrogen.
      Further study showed that the expression of Tnfaip1 in the hippocampus was
      significantly increased in ovariecto-mized mice compared to Sham mice. In
      cultured primary hippocampal cells, Tnfaip1 showed different expression levels in
      different treatments of estrogen or estrogen receptor antagonists. Additional
      experiments demonstrated the existence of a binding site of ERbeta in the Tnfaip1
      promoter region, and that ERbeta was able to upregulate Tnfaip1 expression. Our
      study identified a new regulatory factor and a primary regulatory mechanism of
      Tnfaip1 expression in hippocampus. Since both hippocampus and estrogen are
      crucial in AD, the results also showed a potential association between Tnfaip1
      and hippocampal-related diseases, such as AD, which may be affected by the
      estrogen level.

PMID- 24737447
TI  - Risk factors and management of positive horizontal margin in early gastric cancer
      resected by en bloc endoscopic submucosal dissection.
AB  - BACKGROUND: Although endoscopic submucosal dissection (ESD) is a widely accepted
      treatment for early gastric cancer (EGC), there is no consensus regarding the
      management of positive horizontal margin (HM) despite en bloc ESD. The aim of the
      current study was to identify the risk factors and optimal management of positive
      HM in EGCs resected by en bloc ESD. METHODS: A total of 890 consecutive patients
      with 1,053 intramucosal EGCs resected by en bloc ESD between April 2005 and June
      2011. Clinicopathological data were retrieved retrospectively to assess the
      positive HM rate, local recurrence rate, risk factors for positive HM, and
      outcomes of treatment for local recurrent tumor. Positive HM was defined as a
      margin with direct tumor invasion (type A), the presence of cancerous cells on
      either end of 2-mm-thick cut sections (type B), or an unclear tumor margin
      resulting from crush or burn damage (type C). RESULTS: The positive HM rate was
      2.0% (21/1,053). The local recurrence rate was 0.3% (3/1,053). All local
      recurrent tumors were intramucosal carcinomas, and were resected curatively by re
      ESD. Multivariate analysis with logistic regression showed tumor location in the
      upper third of the stomach and lesions not matching the absolute indication to be
      independent risk factors for positive HM. CONCLUSION: The risk factors for HM
      positivity in cases of EGC resected by en bloc ESD are tumor location in the
      upper third of the stomach and dissatisfaction of the absolute indication for
      curative ESD.

PMID- 24737448
TI  - IL-25 exhibits disparate roles during Th2-cell differentiation versus effector
      function.
AB  - A keenly sought therapeutic approach for the treatment of allergic disease is the
      identification and neutralization of the cytokine that regulates the
      differentiation of T helper 2 (Th2) cells. Th2 cells are exciting targets for
      asthma therapies. Recently, the cytokine IL-25 has been shown to enhance Th2-type
      immune activity and play important roles in mediating allergic inflammatory
      responses. To investigate this further, we crossed IL-25(-/-) C57BL/6 mice with
      G4 IL-4 C57BL/6 reporter mice and developed an assay for in vitro and in vivo IL
      4-independent Th2-cell differentiation. These assays were used to determine
      whether IL-25 was critical for the formation of Th2 cells. We found there was no
      physiological role for IL-25 in either the differentiation of Th2 cells or their
      development to effector or memory Th2-cell subsets. Importantly, this data
      challenges the newly found and growing status of the cytokine IL-25 and its
      proposed role in promoting Th2-cell responses. 

PMID- 24737446
TI  - Hyperglycemia / hypoglycemia-induced mitochondrial dysfunction and cerebral
      ischemic damage in diabetics.
AB  - Enhancement of ischemic brain damage is one of the most serious complications of
      diabetes. Studies from various in vivo and in vitro models of cerebral ischemia
      have led to an understanding of the role of mitochondria and complex interrelated
      mitochondrial biochemical pathways leading to the aggravation of ischemic
      neuronal damage. Advancements in the elucidation of the mechanisms of ischemic
      brain damage in diabetic subjects have revealed a number of key mitochondrial
      targets that have been hypothesized to participate in enhancement of brain
      damage. The present review initially discusses the neurobiology of ischemic
      neuronal injury, with special emphasis on the central role of mitochondria in
      mediating its pathogenesis and therapeutic targets. Later it further details the
      potential role of various biochemical mediators and second messengers causing
      widespread ischemic brain damage among diabetics via mitochondrial pathways. The
      present review discusses preclinical data which validates the significance of
      mitochondrial mechanisms in mediating the aggravation of ischemic cerebral injury
      in diabetes. Exploitation of these targets may provide effective therapeutic
      agents for the management of diabetes-related aggravation of ischemic neuronal
      damage. 

PMID- 24737449
TI  - microRNA-145 inhibits cell proliferation, migration and invasion by targeting
      matrix metallopeptidase-11 in renal cell carcinoma.
AB  - microRNA-145 (miR-145) has been reported to be frequently downregulated in
      various types of cancer, including renal, prostate, bladder, lung and colon
      cancer, as well as B-cell malignancies. The present study examined the effects of
      miR-145 on the cell proliferation, migration and invasion of renal cell carcinoma
      (RCC). Following transfection of miR-145, an MTT, cell migration, cell invasion
      and luciferase assays, and western blot analysis were conducted in RCC cell
      lines. The present study demonstrated that miR-145 inhibited cell proliferation,
      migration and invasion in 786-O and A498 cells. The present study also
      demonstrated for the first time, to the best of our knowledge, that miR-145 may
      directly target matrix metallopeptidase-11 (MMP-11) in RCC. miR-145 was
      demonstrated to suppress cell proliferation, migration and invasion by targeting
      MMP-11 in RCC cell lines. These results suggested that it may be investigated as
      a predictive marker for the early detection of tumor metastasis and for targeting
      therapeutic drugs to inhibit the invasion of RCC. 

PMID- 24737450
TI  - The effects of black garlic (Allium sativum L.) ethanol extract on the estimated
      total number of Purkinje cells and motor coordination of male adolescent Wistar
      rats treated with monosodium glutamate.
AB  - A number of studies have indicated that monosodium glutamate (MSG) might cause
      negative effects on the nervous system, including in the cerebellum. Garlic
      (Allium sativum) has long been known as a flavouring agent and a traditional
      remedy for various illnesses. The present study aimed at investigating the
      effects of garlic on the motor coordination and the number of Purkinje cells
      present in rats treated with MSG. A total of 25 male Wistar rats aged 4 to 5
      weeks old were used in this study and were divided into five groups, namely a
      negative control (C-) group, which received 0.9 % NaCl solution, a positive
      control (C+) group, which received MSG, and three treated groups, which received
      2 mg/g bw of MSG and 2.5 mg (T2.5), 5 mg (T5), or 10 mg (T10) of black garlic
      solution per oral administration (per 200 g bw), respectively. All treatments
      were carried out for 10 days. Upon the end of the treatment, the motor
      performance of all rats were tested using the rotarod apparatus. The rats were
      subsequently sacrificed, and the cerebella of the rats were processed for
      stereological analyses. It has been found that the number of Purkinje cells of
      the cerebella of all treated groups were significantly higher than that of the
      group treated with MSG only. No changes in motor coordination function were
      observed as a result of MSG treatment.

PMID- 24737451
TI  - A roadmap to uranium ionic liquids: anti-crystal engineering.
AB  - In the search for uranium-based ionic liquids, tris(N,N
      dialkyldithiocarbamato)uranylates have been synthesized as salts of the 1-butyl-3
      methylimidazolium (C4mim) cation. As dithiocarbamate ligands binding to the
      UO2(2+) unit, tetra-, penta-, hexa-, and heptamethylenedithiocarbamates, N,N
      diethyldithiocarbamate, N-methyl-N-propyldithiocarbamate, N-ethyl-N
      propyldithiocarbamate, and N-methyl-N-butyldithiocarbamate have been explored. X
      ray single-crystal diffraction allowed unambiguous structural characterization of
      all compounds except N-methyl-N-butyldithiocarbamate, which is obtained as a
      glassy material only. In addition, powder X-ray diffraction as well as
      vibrational and UV/Vis spectroscopy, supported by computational methods, were
      used to characterize the products. Differential scanning calorimetry was employed
      to investigate the phase-transition behavior depending on the N,N
      dialkyldithiocarbamato ligand with the aim to establish structure-property
      relationships regarding the ionic liquid formation capability. Compounds with the
      least symmetric N,N-dialkyldithiocarbamato ligand and hence the least symmetric
      anions, tris(N-methyl-N-propyldithiocarbamato)uranylate, tris(N-ethyl-N
      propyldithiocarbamato)uranylate, and tris(N-methyl-N
      butyldithiocarbamato)uranylate, lead to the formation of (room-temperature) ionic
      liquids, which confirms that low-symmetry ions are indeed suitable to suppress
      crystallization. These materials combine low melting points, stable complex
      formation, and hydrophobicity and are therefore excellent candidates for nuclear
      fuel purification and recovery.

PMID- 24737457
TI  - Occipital neuralgia.
AB  - Occipital pain is a common complaint amongst patients with headache, and the
      differential can include many primary headache disorders such as cervicogenic
      headache or migraine. Occipital neuralgia is an uncommon cause of occipital pain
      characterized by paroxysmal lancinating pain in the distribution of the greater,
      lesser or third occipital nerves. Greater occipital nerve blockade with
      anesthetics and/or corticosteroids can aid in confirming the diagnosis and
      providing pain relief. However, nerve blocks are also effective in migraine
      headache and misdiagnosis can result in a false positive. Physical therapy and
      preventive medication with antiepileptics and tricyclic antidepressants are often
      effective treatments for occipital neuralgia. Refractory cases may require
      intervention with pulsed radiofrequency or occipital nerve stimulation. 

PMID- 24737458
TI  - Genetically predicted 17beta-estradiol and systemic inflammation in women: a
      separate-sample Mendelian randomisation analysis in the Guangzhou Biobank Cohort
      Study.
AB  - BACKGROUND: Many chronic diseases are characterised by low-grade systemic
      inflammation. Oestrogens may promote immune response consistent with sex-specific
      patterns of diseases. In vitro culture and animal experiments suggest oestrogens
      are anti-inflammatory and might thereby protect against low-grade systemic
      inflammation. Evidence from epidemiological studies is limited. Using a Mendelian
      randomisation analysis with a separate-sample instrumental variable (SSIV)
      estimator, we examined the association of genetically predicted 17beta-estradiol
      with well-established systemic inflammatory markers (total white cell count,
      granulocyte and lymphocyte count). METHODS: A genetic score predicting 17beta
      estradiol was developed in 237 young Chinese women (university students) from
      Hong Kong based on a parsimonious set of genetic polymorphisms (ESR1 (rs2175898)
      and CYP19A1 (rs1008805)). Multivariable linear regression was used to examine the
      association of genetically predicted 17beta-estradiol with systemic inflammatory
      markers among 3096 older (50+ years) Chinese women from the Guangzhou Biobank
      Cohort Study. RESULTS: Predicted 17beta-estradiol was negatively associated with
      white blood cell count (-6.3 10(3)/mL, 95% CI -11.4 to -1.3) and granulocyte
      count (-4.5 10(3)/mL, 95% CI -8.5 to -0.4) but not lymphocyte count (-1.5
      10(3)/mL, 95% CI -3.4 to 0.4) adjusted for age only. Results were similar further
      adjusted for education, smoking, use of alcohol, physical activity, Body Mass
      Index, waist-hip ratio, age of menarche, age at menopause, use of hormonal
      contraceptives and hormone replacement therapy. CONCLUSIONS: Endogenous
      genetically predicted 17beta-estradiol reduced low-grade systemic inflammatory
      markers (white blood cell count and granulocyte count), consistent with
      experimental and ecological evidence of 17beta-estradiol promoting immune
      response. Replication in a larger sample is required.

PMID- 24737459
TI  - Clinical profile and prognostic value of anemia at the time of admission and
      discharge among patients hospitalized for heart failure with reduced ejection
      fraction: findings from the EVEREST trial.
AB  - BACKGROUND: Anemia has been associated with worse outcomes in patients with
      chronic heart failure (HF). We aimed to characterize the clinical profile and
      postdischarge outcomes of hospitalized HF patients with anemia at admission or
      discharge. METHODS AND RESULTS: An analysis was performed on 3731 (90%) of 4133
      hospitalized HF patients with ejection fraction <=40% enrolled in the Efficacy of
      Vasopressin Antagonist in Heart Failure Outcome Study with Tolvaptan (EVEREST)
      trial with baseline hemoglobin data, comparing the clinical characteristics and
      outcomes (all-cause mortality and cardiovascular mortality or HF hospitalization)
      of patients with and without anemia (hemoglobin <12 g/dL for women and <13 g/dL
      for men) on admission or discharge/day 7. Overall, 1277 patients (34%) were
      anemic at baseline, which persisted through discharge in 73% and resolved in 27%;
      6% of patients without baseline anemia developed anemia by discharge or day 7.
      Patients with anemia were older, with lower blood pressure, and higher creatinine
      and natriuretic peptide levels compared with those without anemia (all P<0.05).
      After risk adjustment, anemia at discharge, but not admission, was independently
      associated with increased all-cause mortality (hazard ratio, 1.30; 95% confidence
      interval, 1.05-1.60; P=0.015; and hazard ratio, 0.94; 95% confidence interval,
      0.76-1.15; P=0.53, respectively) and cardiovascular mortality plus HF
      hospitalization early postdischarge (<=100 days; hazard ratio 1.73; 95%
      confidence interval, 1.37-2.18; P<0.001; and hazard ratio, 0.92; 95% confidence
      interval, 0.73-1.16; P=0.47, respectively). Neither baseline nor discharge anemia
      was associated with long-term cardiovascular mortality plus HF hospitalization
      (>100 days) on adjusted analysis (both P>0.1). CONCLUSIONS: Among hospitalized HF
      patients with reduced ejection fraction, modest anemia at discharge but not
      baseline was associated with increased all-cause mortality and short-term
      cardiovascular mortality plus HF hospitalization. CLINICAL TRIAL REGISTRATION:
      URL: http://www.clinicaltrials.gov. Unique identifier: NCT00071331.

PMID- 24737460
TI  - Memantine improves attention and episodic memory in Parkinson's disease dementia
      and dementia with Lewy bodies.
AB  - OBJECTIVE: In both dementia with Lewy bodies (DLB) and Parkinson's disease
      dementia (PDD), attentional dysfunction is a core clinical feature together with
      disrupted episodic memory. This study evaluated the cognitive effects of
      memantine in DLB and PDD using automated tests of attention and episodic memory.
      METHODS: A randomised double-blind, placebo-controlled, 24-week three centre
      trial of memantine (20 mg/day) was conducted in which tests of attention (simple
      and choice reaction time) and word recognition (immediate and delayed) from the
      CDR System were administered prior to dosing and again at 12 and 24 weeks.
      Although other results from this study have been published, the data from the CDR
      System tests were not included and are presented here for the first time.
      RESULTS: Data were available for 51 patients (21 DLB and 30 PDD). In both
      populations, memantine produced statistically significant medium to large effect
      sized improvements to choice reaction time, immediate and delayed word
      recognition. CONCLUSIONS: These are the first substantial improvements on
      cognitive tests of attention and episodic recognition memory identified with
      memantine in either DLB or PDD.

PMID- 24737461
TI  - Interkeukin-34, a cytokine crucial for the differentiation and maintenance of
      tissue resident macrophages and Langerhans cells.
AB  - IL-34 is a recently discovered cytokine that acts on tissue resident macrophages
      and Langerhans cells upon binding the receptor for CSF-1, CSF-1R. The existence
      of two ligands for CSF-1R, IL-34, and CSF-1, raises several intriguing questions.
      Are IL-34 and CSF-1 redundant or does each perform temporally and spatially
      distinct functions? Is IL-34 involved in human pathology? Would therapeutic
      strategies based on selective inhibition or administration of either IL-34 or CSF
      1 be advantageous for preventing human pathology? Recent in vivo studies indicate
      that IL-34 promotes the development, survival, and function of microglia and
      Langerhans cells; therefore, this cytokine may predominately function in brain
      and skin biology. Here, we review the evidence for IL-34 as a key cytokine in the
      development and function of these two diverse cell types and discuss its
      potential role in pathological conditions. 

PMID- 24737462
TI  - Worker assessments of organizational practices and psychosocial work environment
      are associated with musculoskeletal injuries in hospital patient care workers.
AB  - BACKGROUND: Hospital patient care (PC) workers have high rates of workplace
      injuries, particularly musculoskeletal injuries. Despite a wide spectrum of
      documented health hazards, little is known about the association between
      psychosocial factors at work and OSHA-recordable musculoskeletal injuries.
      METHODS: PC-workers (n = 1,572, 79%) completed surveys assessing a number of
      organizational, psychosocial and psychological variables. Associations between
      the survey responses and injury records were tested using bivariate and
      multivariate analyses. RESULTS: A 5% of the PC-workers had at least one OSHA
      recordable musculoskeletal injury over the year, and the injuries were
      significantly associated with: organizational factors (lower people-oriented
      culture), psychosocial factors (lower supervisor support), and structural factors
      (job title: being a patient care assistant). CONCLUSIONS: The results show
      support for a multifactorial understanding of musculoskeletal injuries in
      hospital PC-workers. An increased focus on the various dimensions associated with
      injury reports, particularly the organizational and psychosocial factors, could
      contribute to more efficient interventions and programs.

PMID- 24737463
TI  - Characterisation of radicals formed by the triazine 1,4-dioxide hypoxia-activated
      prodrug, SN30000.
AB  - The radical species underlying the activity of the bioreductive anticancer
      prodrug, SN30000, have been identified by electron paramagnetic resonance and
      pulse radiolysis techniques. Spin-trapping experiments indicate both an aryl-type
      radical and an oxidising radical, trapped as a carbon-centred radical, are formed
      from the protonated radical anion of SN30000. The carbon-centred radical,
      produced upon the one-electron oxidation of the 2-electron reduced metabolite of
      SN30000, oxidises 2-deoxyribose, a model for the site of damage on DNA which
      leads to double strand breaks. Calculations using density functional theory
      support the assignments made. 

PMID- 24737464
TI  - Assessing the feasibility of full robotic interaortocaval nodal dissection for
      locally advanced gastric cancer.
AB  - BACKGROUND: The clinical value of super-extended lymph node dissection (D2(+) )
      is still debated. This procedure has not been reported using the laparoscopic or
      robotic approach. Although this technique, in low-volume centres, could lead to
      an increased risk of morbidity, in high-volume centres morbidity and mortality
      are similar to those of the standard D2 lymphadenectomy. Robotic surgery could
      overcome the limitations of laparoscopic surgery, especially in the removal of
      posterior nodal stations. In this report we describe the feasibility of fully
      robotic interaortocaval lymphadenectomy, following similar steps to those of the
      traditional open approach. METHODS: The procedure was a total gastrectomy with
      oesophago-jejunal Roux-en-Y reconstruction in a 73 year-old male patient with
      clinically advanced (cT3) gastric adenocarcinoma, located in the lesser curvature
      (middle-upper third). The da Vinci(r) Si HD with a double-docking robot set-up
      was employed. RESULTS: The histological specimen examination showed a pT4aN3bM0,
      Borrmann type III, intestinal histotype, G3 gastric adenocarcinoma. No
      involvement of resection margins was found (R0 resection). The numbers of total
      harvested and positive nodes were 57 and 41, respectively; the number of
      harvested interaortocaval nodes was 14, and all of them were negative for tumour
      involvement. Operative time for lymphadenectomy was comparable with that of the
      traditional open approach. The postoperative period was uneventful and hospital
      stay was 11 days. CONCLUSIONS: Robotic-assisted interaortocaval lymphadenectomy
      is a feasible technique in high-volume centres for gastric cancer surgery, and
      should be considered in curative surgery for selected advanced cases, especially
      for the high-risk group of lymph node metastases in the posterior area.

PMID- 24737465
TI  - Cloning and expression analysis of the Lonicera japonica Thunb. chlorogenic acid
      synthetase gene (LjCCoAOMT1) in rice.
AB  - Complete coding DNA sequences of a closely related chlorogenic acid synthetase
      gene (LjCCoAOMT1) were isolated from Lonicera japonica Thunb. by reverse
      transcription polymerase chain reaction (RT-PCR) and rapid amplification of cDNA
      ends (RACE). LjCCoAOMT1 was subsequently overexpressed in Escherichia coli and a
      25-kD protein was detected by electrophoresis and western blot analysis. High
      performance liquid chromatography (HPLC) analysis showed that recombinant
      LjCCoAOMT1 methylates the caffeic acid substrate to generate ferulic acid.
      Further analysis showed that the chlorogenic acid content was significantly
      correlated with the expression level of LjCCoAOMT1 in various tissues of L.
      japonica Thunb. at different developmental stages. A plant expression vector
      containing LjCCoAOMT1 was constructed and Agrobacterium-mediated transgenic rice
      was successfully obtained. Light treatment analysis showed that LjCCoAOMT1
      transgenic rice was more sensitive than wild-type rice in responding to the
      changes in lighting conditions. Although gibberellic acid (GA3) could promote the
      growth of both wild-type and LjCCoAOMT1 transgenic rice, LjCCoAOMT1 transgenic
      rice appeared to be more sensitive to GA3. Furthermore, high concentrations of
      GA3 significantly facilitated the growth of LjCCoAOMT1 transgenic rice.

PMID- 24737466
TI  - Chromosomal localization and partial sequencing of the 18S and 28S ribosomal
      genes from Bradysia hygida (Diptera: Sciaridae).
AB  - In insects, ribosomal genes are usually detected in sex chromosomes, but have
      also or only been detected in autosomal chromosomes in some cases. Previous
      results from our research group indicated that in Bradysia hygida, nucleolus
      organizer regions were associated with heterochromatic regions of the autosomal C
      chromosome, using the silver impregnation technique. The present study confirmed
      this location of the ribosomal genes using fluorescence in situ hybridization
      analysis. This analysis also revealed the partial sequences of the 18S and 28S
      genes for this sciarid. The sequence alignment showed that the 18S gene has 98%
      identity to Corydalus armatus and 91% identity to Drosophila persimilis and
      Drosophila melanogaster. The partial sequence analysis of the 28S gene showed 95%
      identity with Bradysia amoena and 93% identity with Schwenckfeldina sp. These
      results confirmed the location of ribosomal genes of B. hygida in an autosomal
      chromosome, and the partial sequence analysis of the 18S and 28S genes
      demonstrated a high percentage of identity among several insect ribosomal genes. 

PMID- 24737467
TI  - Physical mapping of 18S rDNA and heterochromatin in species of family Lygaeidae
      (Hemiptera: Heteroptera).
AB  - Analyses conducted using repetitive DNAs have contributed to better understanding
      the chromosome structure and evolution of several species of insects. There are
      few data on the organization, localization, and evolutionary behavior of
      repetitive DNA in the family Lygaeidae, especially in Brazilian species. To
      elucidate the physical mapping and evolutionary events that involve these
      sequences, we cytogenetically analyzed three species of Lygaeidae and found 2n
      (?) = 18 (16 + XY) for Oncopeltus femoralis; 2n (?) = 14 (12 + XY) for Ochrimnus
      sagax; and 2n (?) = 12 (10 + XY) for Lygaeus peruvianus. Each species showed
      different quantities of heterochromatin, which also showed variation in their
      molecular composition by fluorochrome staining. Amplification of the 18S rDNA
      generated a fragment of approximately 787 bp. The alignment of the consensus
      sequence with sequences from other species of Heteroptera deposited in the
      GenBank revealed a similarity of 98% with small differences. Fluorescent in situ
      hybridization with the 18S rDNA fragment revealed that this ribosomal gene was
      located in 1 autosomal pair at different positions in the three species. No
      cytogenetic data are available for these Brazilian species. The basal number and
      the possible chromosomal changes that occurred among the different species, as
      well as the evolution of these DNA sequences, are discussed. 

PMID- 24737468
TI  - Association of neural tube defects in children of mothers with MTHFR 677TT
      genotype and abnormal carbohydrate metabolism risk: a case-control study.
AB  - Abnormalities in maternal folate and carbohydrate metabolism have both been shown
      to induce neural tube defects (NTD) in humans and animal models. However, the
      relationship between these two factors in the development of NTDs remains
      unclear. Data from mothers of children with spina bifida seen at the Unidad de
      Espina Bifida del Hospital Infantil Virgen del Rocio (case group) were compared
      to mothers of healthy children with no NTD (control group) who were randomly
      selected from patients seen at the outpatient ward in the same hospital. There
      were 25 individuals in the case group and 41 in the control group. Analysis of
      genotypes for the methylenetetrahydrofolate reductase (MTHFR) 677CT polymorphism
      in women with or without risk factors for abnormal carbohydrate metabolism
      revealed that mothers who were homozygous for the MTHFR 677TT polymorphism and at
      risk of abnormal carbohydrate metabolism were more likely to have offspring with
      spina bifida and high levels of homocysteine, compared to the control group. The
      increased incidence of NTDs in mothers homozygous for the MTHFR 677TT
      polymorphism and at risk of abnormal carbohydrate metabolism stresses the need
      for careful metabolic screening in pregnant women, and, if necessary,
      determination of the MTHFR 677CT genotype in those mothers at risk of developing
      abnormal carbohydrate metabolism. 

PMID- 24737469
TI  - Study of Hgp44 from Porphyromonas gingivalis on inducing HUVECs to secrete IL-6
      and IL-8.
AB  - The aim of this study was to clone, express the gene of Hgp44 in adhesin domains
      of gingipains from Porphyromonas gingivalis and purify the protein. Furthermore,
      the effect of Hgp44 from P. gingivalis on inducing HUVECs to secrete IL-6 and IL
      8 was evaluated. The Hgp44 gene fragment was amplified by polymerase chain
      reaction, and then inserted into the cloning vector pMD18-T and linked with a
      prokaryotic expression vector pET22b to construct the recombinant expression
      plasmid pET22b-Hgp44. Fusion protein expression was induced by IPTG, and it was
      purified by immobilized metal-chelating affinity chromatography (IMAC) using an
      Ni(2+) matrix column. HUVECs were cultured in vitro and different concentrations
      of Hgp44 were added to confluent HUVEC monolayers and incubated for 2, 8 and 24
      h. We extracted the supernatants and then used ELISA kits to test the changes in
      IL-6 and IL-8 levels. Finally, a 1100-bp fragment was successfully amplified, and
      the expression of the fusion protein was examined by SDS-PAGE and Western blot
      analysis, and the data showed that the protein was 44 kDa in size and expressed
      mostly in the form of inclusion bodies. The purification of the fusion protein
      was achieved using Ni(2+) affinity chromatography. About 3.5 mg/L fusion protein
      was obtained. Hgp44 could induce HUVECs to secrete IL-6 and IL-8 levels, which
      were remarkably increased. In a word, Hgp44 was successfully expressed in a
      prokaryotic expression system and purified by IMAC using the Ni(2+) matrix
      column. The effect of Hgp44 in inducing HUVECs to secrete IL-6 and IL-8 was
      demonstrated.

PMID- 24737470
TI  - Characterization of EST-derived and non-EST simple sequence repeats in an F1
      hybrid population of Vitis vinifera L.
AB  - Among different classes of molecular markers, expressed sequence tags (ESTs) are
      a new resource for developing simple sequence repeat (SSR) functional markers for
      genotyping and genetic mapping in F1 hybrid populations of Vitis vinifera L.
      Recently, because of the availability of an enormous amount of data for ESTs in
      the public domain, the emphasis has shifted from genomic SSRs to EST-SSRs, which
      belong to transcribed regions of the genome and may have a role in gene
      expression or function. The objective of this study was to assess the
      polymorphisms among 94 F1 hybrids from "Early Rose" and "Red Globe" using 25 EST
      derived and 25 non-EST SSR markers. A total collection of 362,375 grape ESTs that
      were retrieved from the National Center for Biotechnology Information (NCBI) and
      2522 EST-SSR sequences were identified. From them, 205 primer pairs were randomly
      selected, including 176 pairs that were EST-derived and 29 non-EST SSR primer
      pairs, for polymerase chain reaction amplification. A total of 131 alleles were
      amplified using 50 pairs of primers; 78 alleles were amplified using EST-derived
      SSR primers and 53 were from non-EST SSR primers. At most, 6 and 5 alleles were
      amplified by EST-derived and non-EST SSR primers, respectively. The EST-derived
      SSR markers showed a maximum polymorphic information content (PIC) value of 1 and
      a minimum of 0.33 while non-EST SSR markers had maximum and minimum PIC values of
      1 and 0.25, respectively. The average PIC value was 0.56 for EST-derived SSR
      markers and 0.45 for non-EST SSR markers. 

PMID- 24737472
TI  - Association between BMP-2 and COL6A1 gene polymorphisms with susceptibility to
      ossification of the posterior longitudinal ligament of the cervical spine in
      Korean patients and family members.
AB  - COL6A1 and BMP-2 genes have been implicated in ossification of the posterior
      longitudinal ligament (OPLL) susceptibility in Japanese and Chinese Han
      populations. However, no study has yet investigated the DNA of unaffected family
      members of patients with OPLL. This study investigated differences in genetic
      polymorphisms of BMP-2 and COL6A1 between Korean patients with OPLL and their
      family members (with and without OPLL). A total of 321 subjects (110 patients
      with OPLL and 211 family members) were enrolled in the study. Associations
      between two single nucleotide polymorphisms (SNPs) of the BMP-2 gene (Ser37Ala
      and Ser87Ser) and two SNPs of COL6A1 [promoter (-572) and intron 33 (+20)] with
      susceptibility to OPLL of the cervical spine were investigated between the two
      groups (OPLL+ and OPLL-). Of the 321 subjects, 162 had cervical OPLL (50.4%; 110
      patients, 52 family members). There was a familial tendency of OPLL in 34 of the
      110 families (30.9%). Allele and haplotype frequencies of the four SNPs in the
      BMP-2 and COL6A1 genes did not differ significantly between the OPLL+ and OPLL-
      groups, even when excluding participants over 50 years of age. This is the first
      report identifying SNPs of COL6A1 and BMP-2 in Korean patients and family members
      with OPLL. Although allele and haplotype frequencies were similar with those of a
      previous study in Japanese and Chinese patients, unaffected family members also
      showed similar rates of these SNPs in the present study. These results suggest
      that these SNPs may not directly influence the expression of OPLL.

PMID- 24737471
TI  - EZH2 suppresses hepatocellular differentiation of mouse bone marrow mesenchymal
      stem cells.
AB  - Our previous studies have indicated that mouse bone marrow mesenchymal stem cells
      (mBMMSCs) have potential to differentiate into hepatocytes with high efficiency.
      Our study aimed to evaluate the role of the mouse histone methyltransferase
      enhancer of zeste homolog 2 gene (EZH2) in the hepatocellular differentiation of
      mBMMSCs. The mBMMSCs isolated from femurs and tibias were cultured in Iscove's
      modified Eagle's medium (IMEM) supplemented with 10% fetal bovine serum.
      Hepatocellular differentiation was induced by 20 ng/mL hepatocyte growth factor
      and 10 ng/mL fibroblast growth factor 4. The mouse histone methyltransferase EZH2
      gene was introduced via PLenti-eGFP-EZH2 or PLenti-eGFP-NEO as a control.
      Hepatocellular-induced mBMMSCs showed lower expression of EZH2 and lower level of
      histone H3 lysine 27 trimethylation (H3K27me3) in the AFP and FOXa2 gene promoter
      regions compared to uninduced mBMMSCs. Introduction of EZH2 inhibited
      hepatocellular induction, reduced both the mRNA and protein levels of AFP and
      FOXa2, and increased the level of histone H3K27me3 in the AFP and FOXa2 gene
      promoter regions. In summary, the mouse histone methyltransferase EZH2 gene could
      suppress hepatocellular differentiation of mBMMSCs by increasing the level of
      H3K27me3 in the AFP and FOXa2 gene promoter regions.

PMID- 24737473
TI  - Antimutagenic and radioprotective activities of beta-carotene against the
      biological effects of iodine-131 radiopharmaceutical in Wistar rats.
AB  - Radioactive iodine-131 (131I) is used in the treatment and diagnosis of thyroid
      gland injuries. However, because it emits ionizing radiation, it causes harmful
      effects to cells. Given that beta-carotene (BC) has antioxidant and antigenotoxic
      properties, this study aimed to investigate its radioprotective and antimutagenic
      activity in relation to 131I at the dose that is used to treat hyperthyroidism
      using a test system of bone marrow cells from Wistar rats (Rattus norvegicus).
      The doses were 0.2 mL of 8 mg BC/mL corn oil and 25 MUCi 131I per 100 g body
      weight, and they were given via gavage in acute and subchronic treatments.
      Treatment groups included simultaneous, pre-treatment, post-treatment, and
      continuous treatment types. In all antimutagenic acute treatments, BC had a
      significant antimutagenic/radioprotective activity in relation to 131I. In
      subchronic antimutagenic treatments, BC reduced the damage that was caused by the
      radioisotope; however, this reduction was not statistically significant because
      of the relatively low percentage of chromosomal abnormalities that were observed
      with only 131I compared to the acute treatment. These results demonstrate the
      radioprotective and antimutagenic activity of BC, indicating its use by the
      population, which inevitably is exposed to mutagenic agents, as a means of health
      protection. 

PMID- 24737474
TI  - Genetic variation in ERCC1 and XPF genes and breast cancer risk.
AB  - Breast cancer is one of the most frequently diagnosed cancer in women worldwide,
      and we conducted a case-control study by genotyping seven potentially functional
      SNPs, three in ERCC1 and four in XPF, in a Chinese population of 417 breast
      cancer cases and 417 cancer-free controls. Three SNPs in ERCC1 and four SNPs in
      XPF were genotyped by using the Taqman Universal PCR Master Mix in the
      GeneAmp((r)) PCR System 9700 with Dual 384-Well Sample Block Module, and assays
      were performed on a 384-well plate on the Sequenom MassARRAY platform. We found
      that elevated breast cancer risk was associated with those who had a family
      history of breast cancer and history of breast disease, and those who were over
      25 years old at first full-term pregnancy. We found that decreased risk of breast
      cancer was associated with those who had a history of full-term pregnancies.
      Compared with the ERCC1 rs11615 T/T genotype, a significantly higher risk of
      breast cancer was found in the C/C genotype in codominant and dominant models
      after adjusting for potential risk factors. Similarly, we found that ERCC1
      rs3212986 C/C genotype was associated with an increased risk of breast cancer in
      codominant, dominant and recessive models. Our study indicated that the ERCC1
      rs11615 and rs2298881 polymorphisms are associated with breast cancer in a
      Chinese population. Further studies with large sample size are greatly needed to
      elucidate the SNPs of ERCC1 and XPF genes in the development of breast cancer.

PMID- 24737475
TI  - Paternity identification in sugarcane polycrosses by using microsatellite
      markers.
AB  - Although polycrosses have been used to test the potential of cross-combination of
      a large number of sugarcane parents, the male parent of the half-sib progenies
      produced is unknown. The present study aimed to integrate the molecular marker
      technology to the sugarcane polycross approach by the application of
      microsatellite markers to identify the male parent of 41 elite clones derived
      from polycross families. Ten microsatellite [single sequence repeats (SSRs)]
      primer pairs were used to identify the most likely male parent considering
      markers present in the selected clone but absent in the female parent. The number
      of alleles generated by the 10 microsatellite primer pairs ranged from 102 (cross
      pollination lantern 4) to 120 (cross-pollination lantern 2) with an average of
      113.25 alleles per SSR. The average genetic similarity among the involved parents
      in the polycrosses was 45.9%. The results of the analysis of the SSR markers
      absent in the female parent and present only in the selected clone as well as the
      genetic similarity values allowed the identification of the most likely male
      parent in 73% of the total clones evaluated and also to detect probable
      contaminations. The obtained results highlight the importance of using molecular
      marker technology in the identification and confirmation of the male parent of
      high-performance clones derived from polycrosses in the sugarcane breeding
      programs. 

PMID- 24737476
TI  - Selfing rate estimation in sugarcane under unfavorable natural conditions of
      crossing by using microsatellite markers.
AB  - The self-fertilization or selfing rate estimation using microsatellite markers
      and its impact on survival and selection rate were evaluated in families derived
      from polycrosses that involved parents that were widely used in sugarcane
      breeding in Brazil. These factors were evaluated under unfavorable natural
      conditions of flowering and crossing. After the germination test, the viable
      progeny were taken to the field for survival rate evaluation (4, 6, and 10
      months) and phenotypic selection at plant cane. The selfing rate estimate based
      on microsatellite markers present in the progeny and absent in their female
      parent was 98.5 and 0% for the polycross families derived from IACSP95-5000 and
      SP89-1115, respectively. The survival and selection rates in the last 2
      evaluations were higher for the SP89-1115 outcrossed family than the IACSP95-5000
      selfed family. The IACSP95-5000 cultivar excelled either as pollen donor with
      fertilization capability or viable seed production even under unfavorable natural
      conditions of crossing. The environment influence (temperature and humidity) had
      an important role during the polycross.

PMID- 24737477
TI  - Prader-Willi-like phenotypes: a systematic review of their chromosomal
      abnormalities.
AB  - Prader-Willi syndrome (PWS) is caused by the lack of expression of genes located
      on paternal chromosome 15q11-q13. This lack of gene expression may be due to a
      deletion in this chromosomal segment, to maternal uniparental disomy of
      chromosome 15, or to a defect in the imprinting center on 15q11-q13. PWS is
      characterized by hypotonia during the neonatal stage and in childhood,
      accompanied by a delay in neuropsychomotor development. Overeating, obesity, and
      mental deficiency arise later on. The syndrome has a clinical overlap with other
      diseases, which makes it difficult to accurately diagnose. The purpose of this
      article is to review the Prader-Willi-like phenotype in the scientific literature
      from 2000 to 2013, i.e., to review the cases of PWS caused by chromosomal
      abnormalities different from those found on chromosome 15. A search was carried
      out using the "National Center for Biotechnology Information" (www.pubmed.com)
      and "Scientific Electronic Library Online (www.scielo.br) databases and
      combinations of key words such as "Prader-Willi-like phenotype" and "Prader-Willi
      syndrome phenotype". Editorials, letters, reviews, and guidelines were excluded.
      Articles chosen contained descriptions of patients diagnosed with the PWS
      phenotype but who were negative for alterations on 15q11-q13. Our search found
      643 articles about PWS, but only 14 of these matched with the Prader-Willi-like
      phenotype and with the selected years of publication (2000-2013). If two or more
      articles reported the same chromosomal alterations for Prader-Willi-like
      phenotype, the most recent was chosen. Twelve articles of 14 were case reports
      and 2 reported series of cases. 

PMID- 24737478
TI  - Sequence characterization, polymorphism, and tissue expression profile of an
      effector immediate-early gene: activity-regulated cytoskeletal associated protein
      gene (Arc/Arg3.1) in swamp and river buffalo.
AB  - The activity-regulated cytoskeletal associated protein (Arc/Arg3.1) has been
      implicated in experience-dependent synaptic plasticity and memory formation.
      However, information regarding its coding gene in buffalo remains scarce. In this
      study, the full-length of Arc/Arg3.1 was isolated and characterized (accession
      No. JX491649) and genetic variations of six river buffalo and eight swamp buffalo
      were investigated. A tissue expression profile was obtained using semi
      quantitative reverse transcription-polymerase chain reaction. The coding region
      sequence of Arc/Arg3.1 contained 1191 nucleotides encoding a putative protein of
      396 amino acids with a theoretical isoelectric point (pI) and molecular weight
      (Mw) of 5.4 and 45.2 kDa, respectively. Four polymorphisms (c.63T>C, c.228T>C,
      c.558G>A, and c.625G>C) were found in buffalo; however, only substitution
      c.625G>C was non-synonymous, leading to an amino acid change from Val to Leu at
      the 209th position of the Arc/Arg3.1 protein sequence. Bioinformatics analysis
      revealed that this substitution had no significant effect on Arc/Arg3.1 function
      (subPSEC = -1.4039, Pdeleterious = 0.1685), which indicated that Arc/Arg3.1 was
      highly conserved and functionally important in buffalo. Phylogenetic analysis
      revealed that the gene is closely related to that of Bos taurus and Bos
      grunniens. The gene was moderately expressed in the hypophysis and the placenta;
      it was weakly expressed in the kidney, milk, mammary gland, cerebrum, lung,
      heart, rumen, fat, and uterus; and it was almost silent in the muscle, liver, and
      skin. These findings will provide further insights into the structure and
      function of the immediate-early gene in buffalo. 

PMID- 24737479
TI  - Homology-based cloning and expression analysis of Rf genes encoding PPR
      containing proteins in tobacco.
AB  - As a model plant, mechanisms of the cytoplasmic male sterility/restoration of
      fertility (CMS/Rf) system in tobacco are seldom studied. Using Rf gene sequences
      from other Solanaceae plants and the draft genome of Nicotiana benthamiana,
      degenerate primers were designed to amplify the cDNA pool of N. tomentosiformis.
      In total, six possible Rf sequences were identified, two of which contained base
      deletion mutations. The other four were intact open reading frames, of which
      NtomPPR5 harbored a 3-pentatricopeptide repeat (PPR) motif deletion. Structure
      analysis revealed that they all encoded a PPR-containing protein with putative
      mitochondrial targeting signals at their N-terminus, and they all belong to the P
      subfamily. Phylogenetic analysis showed that all of the Rf-coding PPRs clustered
      together, and recent duplication events might have occurred in tobacco after the
      divergence of the species. Quantitative reverse transcription polymerase chain
      reaction analysis demonstrated that the NtomRfs were expressed in all tissues of
      N. tomentosiformis and (CMS) K326, although the expression levels varied with
      gene, organ, and developmental stage. Furthermore, the expression levels of Rf
      sequences in K326 were lower than those in CMS K326. The molecular basis of the
      CMS/Rf system in tobacco requires further investigation.

PMID- 24737480
TI  - Genetic variability and resistance of cultivars of cowpea [Vigna unguiculata (L.)
      Walp] to cowpea weevil (Callosobruchus maculatus Fabr.).
AB  - The cowpea weevil (Callosobruchus maculatus Fabr.) is the most destructive pest
      of the cowpea bean; it reduces seed quality. To control this pest, resistance
      testing combined with genetic analysis using molecular markers has been widely
      applied in research. Among the markers that show reliable results, the inter
      simple sequence repeats (ISSRs) (microsatellites) are noteworthy. This study was
      performed to evaluate the resistance of 27 cultivars of cowpea bean to cowpea
      weevil. We tested the resistance related to the genetic variability of these
      cultivars using ISSR markers. To analyze the resistance of cultivars to weevil, a
      completely randomized test design with 4 replicates and 27 treatments was
      adopted. Five pairs of the insect were placed in 30 grains per replicate.
      Analysis of variance showed that the number of eggs and emerged insects were
      significantly different in the treatments, and the means were compared by
      statistical tests. The analysis of the large genetic variability in all cultivars
      resulted in the formation of different groups. The test of resistance showed that
      the cultivar Inhuma was the most sensitive to both number of eggs and number of
      emerged adults, while the TE96-290-12-G and MNC99-537-F4 (BRS Tumucumaque)
      cultivars were the least sensitive to the number of eggs and the number of
      emerged insects, respectively.

PMID- 24737482
TI  - Artificial intelligence and robot responsibilities: innovating beyond rights.
AB  - The enduring innovations in artificial intelligence and robotics offer the
      promised capacity of computer consciousness, sentience and rationality. The
      development of these advanced technologies have been considered to merit rights,
      however these can only be ascribed in the context of commensurate
      responsibilities and duties. This represents the discernable next-step for
      evolution in this field. Addressing these needs requires attention to the
      philosophical perspectives of moral responsibility for artificial intelligence
      and robotics. A contrast to the moral status of animals may be considered. At a
      practical level, the attainment of responsibilities by artificial intelligence
      and robots can benefit from the established responsibilities and duties of human
      society, as their subsistence exists within this domain. These responsibilities
      can be further interpreted and crystalized through legal principles, many of
      which have been conserved from ancient Roman law. The ultimate and unified goal
      of stipulating these responsibilities resides through the advancement of mankind
      and the enduring preservation of the core tenets of humanity. 

PMID- 24737481
TI  - The rise and fall of prostate brachytherapy: use of brachytherapy for the
      treatment of localized prostate cancer in the National Cancer Data Base.
AB  - BACKGROUND: Brachytherapy has been shown to be an efficacious and cost-effective
      treatment among patients with localized prostate cancer. In this study, the
      authors examined trends in brachytherapy use for localized prostate cancer using
      a large national cancer registry. METHODS: In the National Cancer Data Base
      (NCDB), a total of 1,547,941 patients with localized prostate cancer were
      identified from 1998 through 2010. Excluding patients with lymph node-positive or
      metastatic disease, the authors examined primary treatment trends focusing on the
      use of brachytherapy over time. Patients with available data (2004-2009) were
      stratified by National Comprehensive Cancer Network risk criteria. Controlling
      for year of diagnosis and demographic, clinical, and pathologic characteristics,
      multivariate analyses were performed examining the association between patient
      characteristics and receipt of brachytherapy. RESULTS: In the study cohort,
      brachytherapy use reached a peak of 16.7% in 2002, and then steadily declined to
      a low of 8% in 2010. Of the 719,789 patients with available data for risk
      stratification, 41.1%, 35.3%, and 23.6%, respectively, met low, intermediate, and
      high National Comprehensive Cancer Network risk criteria. After adjustment,
      patients of increasing age and those with Medicare insurance were more likely to
      receive brachytherapy. In contrast, patients with intermediate-risk or high-risk
      disease, Medicaid insurance, increasing comorbidity count, and increasing year of
      diagnosis were less likely to receive brachytherapy. CONCLUSIONS: For patients
      with localized prostate cancer who are treated at National Cancer Data Base
      institutions, there has been a steady decline in brachytherapy use since 2003.
      For low-risk patients, the declining use of brachytherapy monotherapy compared
      with more costly emerging therapies has significant health policy implications.

PMID- 24737483
TI  - PAX6, a novel target of miR-335, inhibits cell proliferation and invasion in
      glioma cells.
AB  - Paired box 6 (PAX6), a highly conserved transcription factor, is important in
      glioma. However, the molecular mechanisms involved remain unclear. The present
      study demonstrated that the expression of PAX6 was significantly reduced with the
      malignancy of glioma and also identified PAX6 as a novel target of microRNA (miR)
      335, which was significantly upregulated in glioma. The inhibition of miR-335
      increased the protein expression of PAX6, whereas the upregulation of miR-335
      suppressed its expression in human glioma U251 and U87 cells. Furthermore,
      upregulation of miR-335 promoted U251 cell proliferation, colony formation and
      invasion, which was reversed by the overexpression of PAX6. Furthermore, the
      present study demonstrated that the effect of miR-335 on U251 cell invasion was
      via the modulation of matrix metalloproteinase (MMP)-2 and MMP-9 expression by
      targeting PAX6. In conclusion, the present study demonstrated that PAX6, as a
      novel target of miR-335, has an anti-oncogenic function in glioma, and thus PAX6
      may serve as a therapeutic target for glioma. 

PMID- 24737484
TI  - A comparison of histamine effects on the sympathetic neurotransmission of
      testicular capsule and rat vas deferens.
AB  - Histamine is an important modulatory agent of the sympathetic neurotransmission,
      but its exact action on the testicular capsule or rat vas deferens is not fully
      understood. The present study sought to further investigate the functional
      effects of histamine on the neuronal and exogenous noradrenaline-induced
      contraction of the testicular capsule and rat vas deferens as well as to evaluate
      the contractile properties of this drug. The testicular capsule or vas deferens
      from Wistar rats, 3-4 months old, weighing 300-400 g, was isolated and mounted in
      organ baths for functional experiments. The results indicated that the neuronally
      evoked contraction of the testicular capsule was affected by histamine (10(-10)
      to 10(-8) M) with participation of inhibitory (H3 receptors) and excitatory (H1
      receptors) receptors. Histamine (10(-7) to 10(-4) M) modulated the field
      stimulated vas deferens by excitatory (H2 receptors) and inhibitory (H1
      receptors) receptors. Histamine was able to decrease the tonic response for
      noradrenaline-induced contractions with participation of H1 receptors (testicular
      capsule) and H3 receptors (vas deferens) followed by nitric oxide generation. At
      high concentration, histamine exerts contractile effects in both tissues. In the
      testicular capsule, the histamine-induced contractions were related to H1
      receptor activation followed by release of prostaglandins. In contrast, the
      contractile effects of histamine in the vas deferens were related to H2 receptor
      activation followed by release of catecholamines from sympathetic nerve endings.
      Therefore, our results indicate that histamine induced several effects on the
      sympathetic neurotransmission of rat testicular capsule and vas deferens. These
      effects are dependent on the concentration used and with participation of
      multiple histamine receptors.

PMID- 24737485
TI  - NoSQL data model for semi-automatic integration of ethnomedicinal plant data from
      multiple sources.
AB  - INTRODUCTION: Sharing traditional knowledge with the scientific community could
      refine scientific approaches to phytochemical investigation and conservation of
      ethnomedicinal plants. As such, integration of traditional knowledge with
      scientific data using a single platform for sharing is greatly needed. However,
      ethnomedicinal data are available in heterogeneous formats, which depend on
      cultural aspects, survey methodology and focus of the study. Phytochemical and
      bioassay data are also available from many open sources in various standards and
      customised formats. OBJECTIVE: To design a flexible data model that could
      integrate both primary and curated ethnomedicinal plant data from multiple
      sources. MATERIALS AND METHODS: The current model is based on MongoDB, one of the
      Not only Structured Query Language (NoSQL) databases. Although it does not
      contain schema, modifications were made so that the model could incorporate both
      standard and customised ethnomedicinal plant data format from different sources.
      RESULTS: The model presented can integrate both primary and secondary data
      related to ethnomedicinal plants. Accommodation of disparate data was
      accomplished by a feature of this database that supported a different set of
      fields for each document. It also allowed storage of similar data having
      different properties. CONCLUSION: The model presented is scalable to a highly
      complex level with continuing maturation of the database, and is applicable for
      storing, retrieving and sharing ethnomedicinal plant data. It can also serve as a
      flexible alternative to a relational and normalised database.

PMID- 24737486
TI  - Notoriety bias in a database of spontaneous reports: the example of osteonecrosis
      of the jaw under bisphosphonate therapy in the French national pharmacovigilance
      database.
AB  - PURPOSE: The purpose of this study was to identify a notoriety bias in a database
      of spontaneous reports and its consequences on the calculation of the reporting
      odds ratio (ROR). METHODS: We used the case/noncase methodology to calculate the
      ROR for bisphosphonates and osteonecrosis of the jaw (ONJ) in the French national
      pharmacovigilance database (from 1985 to 2013). To evaluate notoriety bias, drug
      related risk factors for ONJ [as specified in the summary of product
      characteristics (SPC) of bisphosphonates] were systematically scanned for
      notifications of reports of ONJ occurring under bisphosphonate therapy. When a
      risk factor was present, the ONJ was considered as not due to bisphosphonates,
      and a second ROR was calculated under the hypothesis of maximum bias. RESULTS: In
      total, 148 cases of ONJ were reported (143 with bisphosphonates and five
      without). The raw ROR was 3448 (95% confidence interval 1413-8417). After
      analysis of the reports, only 86 had no mention of a risk factor for ONJ. The ROR
      under the maximum bias hypothesis was 87 (95% confidence interval 63-121). Among
      ONJ where chemotherapy was being administered simultaneously to bisphosphonates,
      27 reports did not consider the chemotherapy to be implicated, despite seven of
      these occurring in cases where ONJ was mentioned in the summary of product
      characteristics. CONCLUSIONS: The existence of a notoriety bias has an impact on
      measures of disproportionality. The detection of pharmacovigilance signals might
      be delayed. It is advisable to list all drugs being taken when an adverse drug
      reaction occurs, and not only those known to be associated with the observed
      reaction.

PMID- 24737487
TI  - Identification of a novel mutation in the presenilin 1 gene in a Chinese
      Alzheimer's disease family.
AB  - This study has identified a gene mutation in a Chinese family with Alzheimer's
      disease (AD). Family members were screened by a set of medical examinations and
      neuropsychological tests. Their DNA was extracted from blood cells and sequenced
      for gene mutation in the amyloid precursor protein (APP), the presenilin 1 (PS1)
      and the presenilin 2 (PS2) genes. Genetic analysis showed that the AD patients in
      the family harbored a T to G missense mutation at the position 314 in exon 4 of
      the PS1 gene, resulting in a change of F105C in amino acid sequence. Clinical
      manifestation of these patients included memory loss, counting difficulty,
      personality change, disorientation, dyscalculia, agnosia, aphasia, and apraxia,
      which was similar to that of the familial AD (FAD) patients harboring other PS1
      mutations. We intend to add a novel mutation F105C of the PS1 gene to the pool of
      FAD mutations. With the current available genetic data, mutations of the PS1 gene
      account for the majority of gene mutations in Chinese FAD. 

PMID- 24737488
TI  - Isolation of dendritic-cell-like S100beta-positive cells in rat anterior
      pituitary gland.
AB  - S100beta-protein-positive cells in the anterior pituitary gland appear to possess
      multifunctional properties. Because of their pleiotropic features, S100beta
      positive cells are assumed to be of a heterogeneous or even a non-pituitary
      origin. The observation of various markers has allowed these cells to be
      classified into populations such as stem/progenitor cells, epithelial cells,
      astrocytes and dendritic cells. The isolation and characterization of each
      heterogeneous population is a prerequisite for clarifying the functional
      character and origin of the cells. We attempt to isolate two of the
      subpopulations of S100beta-positive cells from the anterior lobe. First, from
      transgenic rats that express green fluorescent protein (GFP) driven by the
      S100beta protein promoter, we fractionate GFP-positive cells with a cell sorter
      and culture them so that they can interact with laminin, a component of the
      extracellular matrix. We observe that one morphological type of GFP-positive
      cells possesses extended cytoplasmic processes and shows high adhesiveness to
      laminin (process type), whereas the other is round in shape and exhibits low
      adherence to laminin (round type). We successfully isolate cells of the round
      type from the cultured GFP-positive cells by taking advantage of their low
      affinity to laminin and then measure mRNA levels of the two cell types by real
      time polymerase chain reaction. The resultant data show that the process type
      expresses vimentin (mesenchymal cell marker) and glial fibrillary acidic protein
      (astrocyte marker). The round type expresses dendritic cell markers, CD11b and
      interleukin-6. Thus, we found a method for isolating dendritic-cell-like S100beta
      positive cells by means of their property of adhering to laminin. 

PMID- 24737489
TI  - Notch inhibition promotes fetal liver stem/progenitor cells differentiation into
      hepatocytes via the inhibition of HNF-1beta.
AB  - In a previous study, the Notch pathway inhibited with N-[N-(3,5
      difluorophenacetyl)-L-alanyl]-S-phenylglycine t-butyl ester (also called DAPT)
      was shown to promote the differentiation of fetal liver stem/progenitor cells
      (FLSPCs) into hepatocytes and to impair cholangiocyte differentiation. The
      precise mechanism for this, however, was not elucidated. Two mechanisms are
      possible: Notch inhibition might directly up-regulate hepatocyte differentiation
      via HGF (hepatocyte growth factor) and HNF (hepatocyte nuclear factor)-4alpha or
      might impair cholangiocyte differentiation thereby indirectly rendering
      hepatocyte differentiation as the dominant state. In this study, HGF and HNF
      expression was detected after the Notch pathway was inhibited. Although our
      initial investigation indicated that the inhibition of Notch induced hepatocyte
      differentiation with an efficiency similar to the induction via HGF, the results
      of this study demonstrate that Notch inhibition does not induce significant up
      regulation of HGF or HNF-4alpha in FLSPCs. This suggests that Notch inhibition
      induces hepatocyte differentiation without the influence of HGF or HNF-4alpha.
      Moreover, significant down-regulation of HNF-1beta was observed, presumably
      dependent on an impairment of cholangiocyte differentiation. To confirm this
      presumption, HNF-1beta was blocked in FLSPCs and was followed by hepatocyte
      differentiation. The expression of markers of mature cholangiocyte was impaired
      and hepatocyte markers were elevated significantly. The data thus demonstrate
      that the inhibition of cholangiocyte differentiation spontaneously induces
      hepatocyte differentiation and further suggest that hepatocyte differentiation
      from FLSPCs occurs at the expense of the impairment of cholangiocyte
      differentiation, probably being enhanced partially via HNF-1beta down-regulation
      or Notch inhibition. 

PMID- 24737490
TI  - Taiwanese women's process of recovery from stillbirth: a qualitative descriptive
      study.
AB  - The purpose of this qualitative descriptive study was to portray the recovery
      process of Taiwanese women after stillbirth. Data were generated through
      individual in-depth interviews with 21 women selected using purposeful sampling.
      Three stages in an emotional journey of recovery were suffering from silent
      grief, searching for a way out, and achieving peace of mind and mental stability.
      Throughout their journey, the women's overarching concern was where the deceased
      child had gone and whether it was well. Together these stages composed A pathway
      to peace of mind, a mental journey on which women struggled to spiritually
      connect with the lost baby and finally sought a personal pathway to emotional
      peace. Findings can inform healthcare providers in providing culturally sensitive
      care for Taiwanese women to facilitate healing after a stillbirth.

PMID- 24737491
TI  - Cultural scripts: the elusive role of psychotropic drugs in treatment.

PMID- 24737492
TI  - A two-armed lanthanoid-chelating paramagnetic NMR probe linked to proteins via
      thioether linkages.
AB  - Paramagnetic NMR probes provide valuable long-range structural information on
      proteins and protein complexes. A new, stable, two-armed lanthanoid probe is
      reported that can be attached to a protein site-specifically via chemically inert
      thioether linkages. 

PMID- 24737493
TI  - On the frontier between nucleophilic aromatic substitution and catalysis.
AB  - A study on the arylation of heteroatom nucleophiles by using activated
      haloarenes, with or without metal catalysts, is reported. A discussion concerning
      the involvement of traces of metals is presented, supported by an unexpected
      ''ligand'' effect in the absence of added metal catalysts. We believe that the
      frontier between nucleophilic aromatic substitution and catalysis will likely
      prove to be much harder to delimit than is generally thought. 

PMID- 24737495
TI  - Mesenchymal stem cells reduce intervertebral disc fibrosis and facilitate repair.
AB  - Intervertebral disc degeneration is associated with back pain and radiculopathy
      which, being a leading cause of disability, seriously affects the quality of life
      and presents a hefty burden to society. There is no effective intervention for
      the disease and the etiology remains unclear. Here, we show that disc
      degeneration exhibits features of fibrosis in humans and confirmed this in a
      puncture-induced disc degeneration (PDD) model in rabbit. Implantation of bone
      marrow-derived mesenchymal stem cells (MSCs) to PDD discs can inhibit fibrosis in
      the nucleus pulposus with effective preservation of mechanical properties and
      overall spinal function. We showed that the presence of MSCs can suppress
      abnormal deposition of collagen I in the nucleus pulposus, modulating profibrotic
      mediators MMP12 and HSP47, thus reducing collagen aggregation and maintaining
      proper fibrillar properties and function. As collagen fibrils can regulate
      progenitor cell activities, our finding provides new insight to the limited self
      repair capability of the intervertebral disc and importantly the mechanism by
      which MSCs may potentiate tissue regeneration through regulating collagen
      fibrillogenesis in the context of fibrotic diseases.

PMID- 24737494
TI  - Regulation of adipocytes lipolysis by n-3 HUFA in grass carp (Ctenopharyngodon
      idellus) in vitro and in vivo.
AB  - N-3 highly unsaturated fatty acids (n-3 HUFA) have been shown to inhibit body fat
      accumulation in animals. To clarify the mechanism of this fat-lowering effect of
      n-3 HUFA in grass carp (Ctenopharyngodon idellus), two experiments were
      conducted. In experiment 1, isolated grass carp mature adipocytes were incubated
      with docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) at different
      concentrations for 6 h. The release of glycerol to the medium was detected, and
      the expression of the lipolysis-related genes was analyzed. In experiment 2, a 95
      day feeding trial was conducted with two diets formulated with either lard oil
      (as control) or fish oil (supplying n-3 HUFA as treatment) as the main lipid
      source. The glycerol and free fatty acid (FFA) released from the isolated
      adipocytes of both groups were detected after the feeding period. The expression
      of select lipolysis-related genes in adipose tissue was also analyzed. The
      results from experiment 1 showed that the release of glycerol was significantly
      increased by DHA and EPA (P < 0.05). Moreover, the expression of lipolysis
      related genes, such as adipose triglyceride lipase (ATGL), hormone-sensitive
      lipase (HSL), tumor necrosis factor alpha (TNFalpha) and leptin, was also
      significantly elevated in the treatment group (P < 0.05). Experiment 2
      demonstrated that glycerol and FFA release from the isolated adipocytes were
      significantly higher in the treatment group compared to the control group (P <
      0.05). The expression level of ATGL, HSL, TNFalpha and leptin in the treatment
      group was significantly higher than in the control group (P < 0.05). The present
      results provide novel evidence that n-3 HUFAs could regulate grass carp adipocyte
      lipolysis in vitro or in vivo, and the effect might be in part associated with
      their influence on the expression of lipolysis-related genes and lipolysis
      related adipokines genes.

PMID- 24737496
TI  - Construct validity of the mini mental state examination across time in a sample
      with low-education levels: 10-year follow-up of the Bambui Cohort Study of
      Ageing.
AB  - OBJECTIVE: The study aims to investigate whether longitudinal data on the
      structure of the mini mental state examination (MMSE) collected in an older
      Brazilian cohort support factorial invariance over time. DESIGN: Analysis of 10
      year data from a community-based cohort study was performed. SETTING: The study
      took place in Bambui, Brazil. PARTICIPANTS: The study sample comprised 1558
      (89.4%) of all eligible 1742 elderly residents. MEASUREMENTS: A standard
      Brazilian version of the MMSE was used. RESULTS: A five-factor solution
      (developed on the baseline of the cohort) either with no constraints or with
      loadings constrained to equality across time provided a reasonable fit for the
      MMSE. A comparison between both models suggested that the model with no
      constraints was superior. However, the five absolute goodness-of-fit indices
      suggest that the fully constrained model was also adequate and did not differ
      substantively from the model without any restriction. CONCLUSION: The structure
      of the MMSE remained relatively unchanged across the 10 measurement times, thus
      providing evidence for the good construct validity of the scale across time.

PMID- 24737497
TI  - Comparison of hospital costs for single-port and conventional laparoscopic
      colorectal resection: a case-matched study.
AB  - BACKGROUND: Whether single-port laparoscopic (SPL) colorectal resection is cost
      effective in comparison to conventional laparoscopy remains unclear. The aim of
      this study is to compare hospital costs for single-port versus conventional
      laparoscopic colorectal resections. METHODS: Patients with available cost data
      who underwent (SPL) colorectal resection between December 2007 and December 2010
      were matched with conventional (multiport) laparoscopic (CL) counterparts for
      age, gender, American Society of Anesthesiologists score, body mass index,
      operation type and year of surgery. Patients who underwent hand-assisted
      laparoscopic surgery were not included in the study. Direct hospital costs for
      the two groups were compared. RESULTS: There were 90 patients in the SPL group
      and 90 patients in the CL group. Age (p = 0.79), gender (p = 0.88), body mass
      index (p = 0.82), American Society of Anesthesiologists score (p = 1) and
      diagnosis (p = 0.85) were similar in both groups. Operation type (p = 1),
      estimated blood loss (p = 0.17) and length of hospital stay (p = 0.06) were
      comparable between the groups. Operation time was significantly shorter in the
      SPL group (p < 0.001), thus anesthesia cost was significantly lower in this group
      (p = 0.003). Total costs (p = 0.5), operating room (p = 0.65), nursing (p =
      0.13), pharmacy (p = 0.6), radiology (p = 0.27), professional (p = 0.38) and
      pathology/laboratory (p = 0.46) costs were similar between the two groups.
      CONCLUSIONS: Single-port laparoscopic colorectal resection can be performed with
      comparable hospital costs to conventional multiport laparoscopy.

PMID- 24737498
TI  - Lifetime and current pesticide exposure among Latino farmworkers in comparison to
      other Latino immigrants.
AB  - BACKGROUND: Pesticide exposure poses a health risk for farmworkers. This analysis
      documents lifetime and current pesticide exposure of North Carolina Latino
      migrant farmworkers, with comparison to non-farmworker Latino immigrants.
      METHODS: During May to October 2012, 235 Latino farmworkers and 212 Latino non
      farmworkers completed interviews with items to construct measures of lifetime,
      current residential and occupational pesticide exposure. RESULTS: Farmworkers
      experience levels of lifetime and residential pesticide exposure that are
      consistently greater than among non-farmworkers. Farmworkers report a large
      number of occupational pesticide exposures. Lifetime exposure and current
      residential pesticide exposure are related to social determinants. Education is
      inversely related to lifetime pesticide exposure for farmworkers and non
      farmworkers; farmworkers with H-2A visas report greater residential pesticide
      exposure than those without H-2A visas. CONCLUSIONS: Occupational safety policy
      needs to consider these patterns of lifetime exposure when setting standards.
      Health care providers should be aware of the lifetime and current exposure of
      this vulnerable population.

PMID- 24737499
TI  - Transoral robotic surgery for pharyngeal stenosis.
AB  - BACKGROUND: Pharyngeal stenosis is a complication of head and neck cancer and
      sleep apnea treatment that results in functional impairment. Due to the location
      of the stenosis and tendency to recur, surgical management is challenging.
      Robotic surgery may allow these areas to be treated with surgical technique that
      would be difficult using traditional approaches. METHODS: A retrospective chart
      review was performed to identify patients who underwent transoral robotic surgery
      (TORS) for pharyngeal stenosis at a tertiary hospital system. RESULTS: Five
      patients were identified, ages 8-75 years. Length of follow-up ranged from 1-12
      months. There was one failure, a 74 year old male with a history of
      chemoradiation to the area who has required additional procedures. CONCLUSION:
      TORS may offer improved surgical access to the pharynx in patients who require
      complex reconstruction that would otherwise be very difficult. Appropriate
      patient selection is necessary and long-term follow-up is warranted for the
      selected cases.

PMID- 24737500
TI  - Incidence and mechanisms of stroke after permanent carotid artery occlusion
      following temporary occlusion testing.
AB  - BACKGROUND AND PURPOSE: Patients who require sacrifice of the internal carotid
      artery (ICA) have a substantial risk of stroke, despite preoperative testing with
      temporary balloon occlusion (TBO). The purpose of this study is to examine the
      incidence and mechanisms of stroke after permanent carotid artery occlusion in
      this population. METHODS: Consecutive patients undergoing TBO testing from March
      2002 to December 2011 were identified. The protocol included 30 min of balloon
      occlusion, continuous intraprocedural neurological assessment, angiographic
      imaging of collateral flow during the occlusion, and perfusion imaging. Clinical
      records were reviewed for procedure results, procedural complications, and the
      incidence and causes of stroke, transient ischemic attack (TIA) and death over 6
      months. Strokes were categorized as thromboembolic or hypoperfusion based on
      available clinical and imaging data. RESULTS: One hundred and fifty carotid
      occlusion tests were performed during the study period, including 84 women and 66
      men. No procedural strokes were recorded. Thirty-seven patients (25%) had
      permanent occlusion of the tested ICA. Six of the 37 patients had ipsilateral
      stroke (16.2%) and three experienced TIA (8.1%). Two strokes occurred in the
      immediate postoperative period (thromboembolic), two strokes occurred within days
      of ICA occlusion (hypoperfusion), and two strokes occurred at least 30 days from
      the time of ICA occlusion (thromboembolic). CONCLUSIONS: The rate of ischemic
      stroke following carotid sacrifice remains high and most strokes are
      thromboembolic in nature. Our testing protocol did not eliminate the risk of
      hypoperfusion-related stroke. Delayed venous phase by angiography may be a better
      indicator of hemodynamic tolerance than perfusion imaging.

PMID- 24737501
TI  - Watching, but not waiting: vascular neurology perspective on the disparate
      regulatory pathways for stroke.

PMID- 24737502
TI  - Treatment with FLT3 inhibitor in patients with FLT3-mutated acute myeloid
      leukemia is associated with development of secondary FLT3-tyrosine kinase domain
      mutations.
AB  - BACKGROUND: FLT3-internal tandem duplication (ITD) mutations are found in
      approximately 30% of patients with acute myeloid leukemia (AML). FLT3 inhibitors
      have shown clinical activity in AML with FLT3-ITD, but responses are usually
      short-lived. METHODS: This study examined 69 FLT3-mutated patients with AML, who
      were treated with different FLT3 inhibitors to analyze emergence of new
      mutations. RESULTS: At baseline, 87% of patients had an ITD mutation, 7% had a
      D835/I836 mutation, and 6% had combined ITD and D835/I836 mutations. Responses
      occurred in 32% of patients, all with FLT3-ITD; none of the patients with
      D835/I836 or ITD+D835/I836 responded. Mutational assessment at the time of FLT3
      inhibitor discontinuation showed that 68% of patients were unchanged, 10% had
      become undetectable, and 22% of patients progressed from a single ITD to have
      combined ITD+D835/I836 mutations. In those patients with unchanged FLT3 mutation
      at progression, the median survival was 5 months, whereas in those with
      undetectable and with combined ITD+D835/I836 mutations, the median survival was 7
      months, respectively. CONCLUSIONS: These data confirm in vitro observations that
      a secondary tyrosine kinase domain mutation may arise after the use of FLT3
      inhibitors in patients with single FLT3-ITD mutated AML, a phenomenon that is
      associated with resistance and a poor prognosis.

PMID- 24737503
TI  - Reply to the Letter to the editor: Labral injuries of the hip in rowers.

PMID- 24737504
TI  - Temozolomide induces autophagy via ATM-AMPK-ULK1 pathways in glioma.
AB  - Autophagy is a cytoprotective process, which occurs following temozolomide (TMZ)
      treatment, and contributes to glioma chemoresistance and TMZ treatment failure.
      However, the molecular mechanisms by which TMZ induces autophagy are largely
      unknown. In the current study, the ataxia-telangiectasia mutated (ATM) inhibitor
      KU-55933, adenosine monophosphate-activated protein kinase (AMPK) inhibitor
      compound C, and U87MG and U251 cell lines were employed to investigate the
      molecular mechanisms of TMZ-induced autophagy in glioma, and to evaluate the
      effects of autophagy inhibition on TMZ cytotoxicity. KU-55933 and compound C were
      observed to inhibit the activation of autophagy-initiating kinase ULK1 and result
      in a significant decrease of autophagy as indicated by depressed LC3B cleavage
      and acidic vesicular organelle formation. The activation of AMPK-ULK1 was ATM
      dependent. Autophagy inhibition via the AMPK inhibitor compound C augmented TMZ
      cytotoxicity as observed by depressed cell viability, increased gammaH2AX-marked
      double-strand breaks (DSBs) and elevated numbers of apoptotic glioma cells. In
      conclusion, TMZ induced autophagy via ATM-AMPK-ULK1 pathways. TMZ chemoresistance
      may therefore be overwhelmed by targeting AMPK, particularly for the treatment of
      O6-methylguanine DNA methyltransferase-negative gliomas. 

PMID- 24737506
TI  - Effects of atorvastatin in combination with ezetimibe on carotid atherosclerosis
      in elderly patients with hypercholesterolemia.
AB  - The aim of this study was to observe the effects of atorvastatin combined with
      ezetimibe on carotid atherosclerosis in elderly patients with
      hypercholesterolemia. A total of 84 elderly hypercholesterolemic patients
      complicated with carotid atherosclerosis were divided into control group
      (atorvastatin alone) and combined group (atorvastatin combined with ezetimibe)
      and treated for 12 months. Carotid atherosclerosis-related indicators including
      blood lipid and high-sensitivity C-reactive protein (hsCRP) were determined
      before and after treatment. The levels of carotid intima-media thickness (CIMT),
      serum low density lipoprotein cholesterol (LDL-C) and hsCRP were markedly
      decreased (P < 0.05) after treatment in the two groups, while the reduction of
      the levels of CIMT, serum LDL-C and hsCRP was more significant in the combined
      group (P < 0.01). After treatment, the levels of CIMT, serum LDL-C and hsCRP were
      distinctly different between combined and control group (P < 0.05). The
      combination of atorvastatin with ezetimibe could further decrease LDL-C and hsCRP
      levels and have certain effects on the progression of carotid atherosclerosis in
      elderly patients with hypercholesterolemia. 

PMID- 24737505
TI  - Rasgrf2 controls noradrenergic involvement in the acute and subchronic effects of
      alcohol in the brain.
AB  - RATIONALE: Alcohol addiction is a major psychiatric disease, and yet, the
      underlying molecular adaptations in the brain remain unclear. Recent evidence
      suggests a functional role for the ras-specific guanine-nucleotide releasing
      factor 2 (Rasgrf2) in alcoholism. Rasgrf2(-/-) mice consume less alcohol and show
      entirely absent dopamine responses to an alcohol challenge compared to wild types
      (WT). OBJECTIVE: In order to further investigate how Rasgrf2 modifies the acute
      and subchronic effects of alcohol in the brain, we investigated its effects on
      the noradrenergic and serotonergic systems. METHODS: We measured noradrenaline
      and serotonin activity in the brain by in vivo microdialysis and RNA expression
      by chip analysis and RT-PCR after acute and sub-chronic alcohol exposure in
      Rasgrf2(-/-) and WT mice. RESULTS: In vivo microdialysis showed a significantly
      reduced noradrenergic response and an absent serotonergic response in the nucleus
      accumbens (NAcc) and caudate putamen (CPu) after an alcohol challenge in Rasgrf2(
      /-) mice. A co-expression analysis showed that there is a high correlation
      between Rasgrf2 and alpha2 adrenoceptor RNA expression in the ventral striatum in
      naive animals. Accordingly, we further assessed the role of Rasgrf2 in the
      response of the noradrenergic system to subchronic alcohol exposure. A decrease
      in beta1 adrenoceptor gene expression was seen in Rasgrf2(+/+), but not Rasgrf2(
      /-) mice following alcohol exposure. Conversely, alcohol resulted in a decrease
      in both beta2 and alpha2 adrenoceptor gene expression in knockout but not WT
      Rasgrf2 mice. CONCLUSIONS: These findings suggest that adaptations in the
      noradrenergic system contribute to the Rasgrf2 enhanced risk of alcoholism.

PMID- 24737507
TI  - Investigation of a PAX6 gene mutation in a Malaysian family with congenital
      aniridia.
AB  - Mutations in the PAX6 gene that cause aniridia have been identified in various
      ethnicities but not in the Malaysian population. Therefore, the objective of this
      study was to investigate the PAX6 mutation in a Malaysian family with congenital
      aniridia. In this study, a complete ophthalmic examination was performed on a
      Dusun ethnic family with aniridia. Genomic DNA was extracted from the peripheral
      blood of the subjects and screened for the PAX6 gene mutation using polymerase
      chain reaction amplification high-resolution melting curve analysis (PCR-HRM)
      followed by confirmation via direct DNA sequencing. A heterozygous G deletion
      (c.857delG) in exon 7 causing a frame shift in PAX6 was identified in all
      affected family members. Genotype-phenotype correlation analysis revealed
      congenital cataract and all affected family members showed a similar spectrum of
      aniridia with no phenotypic variability but with differences in severity that
      were age-dependent. In summary, by using a PCR-HRM approach, this study is the
      first to report a PAX6 mutation in a Malaysian family. This mutation is the cause
      of the aniridia spectra observed in this family and of congenital cataract. 

PMID- 24737508
TI  - Association analysis between the OPG g.27667T>A genetic variant and bone mineral
      density in Chinese postmenopausal women.
AB  - The purpose of this study was to investigate the association of the g.27667T>A
      genetic variant in the osteoprotegerin (OPG) gene with bone mineral density (BMD)
      and osteoporosis. A total of 393 primary osteoporosis subjects and 402 healthy
      controls were recruited. The BMD of the femoral neck hip, lumbar spine (L2-4),
      and total hip were evaluated by Norland XR-46 dual-energy X-ray absorptiometry.
      The g.27667T>A genetic variant was genotyped using created restriction site
      polymerase chain reaction. Our data indicated significant differences in BMD of
      the femoral neck hip, lumbar spine (L2-4), and total hip among different
      genotypes. Individuals with the genotype TT had significantly higher BMDs than
      those of genotypes TA and AA (P<0.05). Results from this study suggest that the
      g.27667T>A genetic variant in the OPG gene is potentially related to BMD and
      osteoporosis in Chinese postmenopausal women.

PMID- 24737509
TI  - Survey of attitude and knowledge of reproductive health among middle school
      students in Luoyang, China.
AB  - The aim of this study was to assess the knowledge and attitude of AIDS and sexual
      behavior of middle school students. Structural questionnaires were designed to
      interview 1980 junior and senior middle school students about their basic
      knowledge, attitude, and behavior with respect to AIDS and sexual behavior.
      Students were recruited from the six most common middle schools of the six
      regions in Luoyang City of the Henan Province of China by cluster sampling from
      September to December of 2004. Results showed that 54.5% of students had not
      learned about the prevention of HIV/AIDS in school, and 38.3% of students did not
      have any knowledge about the route of transmission of HIV/AIDS. Furthermore,
      91.2% of students were reluctant to share a classroom with HIV/AIDS patients.
      Approximately 21.7% of students had read books, watched videos, and consulted
      other media related to sex, 1.1% of students had had sexual intercourse during
      high school, and 80.5% believed that health education on HIV/AIDS and sex was
      necessary. The results of this survey showed that middle school students have
      little knowledge about HIV/AIDS and sex. Therefore, health education programs for
      HIV/AIDS prevention and sexual health should be developed as soon as possible to
      help students peacefully get through a sexually puzzling period of life.

PMID- 24737510
TI  - Development and characterization of novel SSR markers in Siniperca kneri Garman.
AB  - In this study, 37 transcriptome-derived simple sequence repeat (SSR) markers and
      18 genomic SSR markers were developed and characterized in the Chinese perch,
      Siniperca kneri Garman. The average allele number per locus was 5.1 (range: 2-8)
      for transcriptome-derived SSRs and 3.8 (range: 2-5) for genomic SSRs. The average
      observed and expected heterozygosities were 0.666 (range: 0.000-1.000) and 0.692
      (range: 0.230-0.857) for transcriptome-derived SSRs, respectively. These values
      were 0.380 (range: 0.000-1.000) and 0.527 (range: 0.201-0.799) for genomic SSRs,
      respectively. The average polymorphic information content was 0.638 (range: 0.215
      0.824) for transcriptome-derived SSRs and 0.477 (range: 0.183-0.752) for genomic
      SSRs. Seven of these loci exhibited departure from Hardy-Weinberg equilibrium
      after sequential Bonferroni's correction for multiple tests, and no significant
      deviation was observed for the linkage disequilibrium. These developed and
      characterized markers are anticipated to be useful for studies on population
      genetics, conservation genetics, and the fishery management of this species. 

PMID- 24737511
TI  - Stability and adaptability of grain sorghum hybrids in the off-season.
AB  - We analyzed productivity data obtained from experiments on grain sorghum
      conducted in 7 locations of its cultivation in Brazil. A total of 25 hybrids were
      analyzed, of which 22 were pre-commercial and 3 were cultivars. The Wricke and
      Purchase et al. methods were highly consistent in identifying individuals with
      low contributions to genotype x environment interactions. The Lin and Binns
      method proved to be easily applicable and interpretable but it was not efficient
      in detecting individuals with specific adaptations. An additive main effect and
      multiplicative interaction (AMMI) model indicated the suitability of cultivar
      1G282 for the cities of Guaira, Sete Lagoas, and Vilhena, and hybrids 0307087 and
      0307091 for the southeast of Goias. The associations of the Eberhart and Russell
      method with AMMI indicated that 0307071, 0307131, 0307511, and 0307651 showed
      adaptability to favorable environments. Hybrid 0009061 stood out as the most
      adaptable and stable cultivar. 

PMID- 24737512
TI  - Improvement in the carcass traits and meat quality of growing-finishing Rongchang
      pigs by conjugated linoleic acid through altered gene expression of muscle fiber
      types.
AB  - A total of 160 Rongchang pigs (26.76+/-1.78 kg) were randomly assigned to 5
      dietary treatment groups until their body weight (BW) reached 90 kg. The diets
      were supplemented with 0, 0.5, 1.0, 1.5, and 2.0% conjugated linoleic acid (CLA).
      Our results showed that the 1.0 to 2.0% CLA-fed pigs had less back fat deposition
      when their BW reached 90 kg than the pigs that received less than 1% CLA. During
      the 30 to 60 kg growing period, 1.0, 1.5, and 2.0% CLA treatments improved pork
      quality by significantly reducing the pork pH (P<0.01) and color value (P<0.05),
      but they increased marble scaling (P<0.01). Similarly, the 1.5 and 2.0% CLA-fed
      pigs had more marble than other pigs when their BW reached 90 kg. Furthermore,
      CLA significantly affected the expression of muscle fiber-type genes. The 1.5%
      CLA-fed pigs exhibited the highest mRNA expression of MyHC1 and MyHC2a (P<0.05)
      at 60 kg BW. At 90 kg BW, the highest expression of MyHC1 and MyHC2a (P<0.05) was
      found in the 2.0% CLA group. However, MyHC2x was downregulated in the CLA-fed
      pigs at this time. In addition, CLA supplements did not evidently alter mRNA
      expression of MyHC2b at all times. These results demonstrate that CLA could
      affect carcass traits and improve the meat quality of growing-finishing pigs by
      altering the expression of genes related to muscle growth and development; 1-1.5%
      CLA was the most appropriate CLA dose.

PMID- 24737513
TI  - Prospective study of MTHFR genetic polymorphisms as a possible etiology of male
      infertility.
AB  - The aim of this study was to explore the relationship between 2 genetic
      polymorphisms of the methylenetetrahydrofolate reductase gene (MTHFR), C677T and
      A1298C, and determine the long-term reproductive outcome in infertile men. This
      was a prospective study conducted in an andrology clinic. Men with a 1-year
      history of infertility were assessed for the MTHFR polymorphisms at a 5-year
      follow-up. We compared the MTHFR C677T and A1298C polymorphisms by polymerase
      chain reaction-restriction fragment length polymorphism between men who did and
      did not bear children during follow-up. Of the 215 men who were infertile at 1
      year, 82 (38.1%) remained infertile and 133 (61.9%) achieved natural conception
      during the 5-year follow-up, with the highest rate in the first year (32.6%). The
      MTHFR 677TT genotype (homozygote) was associated with a substantially increased
      risk of infertility during follow-up [odds ratio (OR) = 10.242; 95% confidence
      interval (CI) = 1.257-83.464] relative to the MTHFR 677CC genotype (wild-type).
      Risk of infertility was not increased by the MTHFR A1298C polymorphism alone, but
      was increased by the combination of polymorphisms MTHFR C677T and MTHFR A1298C
      (OR = 11.818; 95%CI = 1.415-98.674). The homozygous MTHFR C677T genotype was a
      risk factor for male infertility during 5-year follow-up, whereas a correlation
      between MTHFR A1298C and infertility was not observed. The MTHFR C677T and MTHFR
      A1298C polymorphisms had additive effects on male infertility.

PMID- 24737514
TI  - Microsatellite markers for the Cabreuva tree, Myroxylon peruiferum (Fabaceae), an
      endangered medicinal species from the Brazilian Atlantic Forest.
AB  - The Cabreuva tree, Myroxylon peruiferum, is an endangered tropical species from
      Brazil used in forest restoration projects. It is known for its medicinal
      properties. Eleven microsatellite markers were developed for this species, from a
      microsatellite-enriched library. Nine of these markers, characterized in 30
      individuals from a semideciduous forest remnant population in southeast Brazil,
      were polymorphic, with allele numbers ranging from 2 to 8 per locus; expected and
      observed heterozygosities ranged from 0.103 to 0.757 and 0.107 to 0.704,
      respectively. One locus (Mpe-C04) showed significant deviation from Hardy
      Weinberg equilibrium, probably due to null alleles. Two other loci (Mpe-E09 and
      Mpe-H07) were monomorphic in this population. These microsatellite loci should be
      useful for future population genetic studies of this species.

PMID- 24737515
TI  - Production and genetic characterization of interspecific hybrids among Crambe
      abyssinica, Crambe hispanica and Crambe kralikii.
AB  - In this paper, interspecific crosses among Crambe abyssinica, Crambe hispanica,
      and Crambe kralikii were reported. In the C. hispanica x C. abyssinica (H x A)
      cross, 118 F1 hybrids were produced without embryo rescue, while 5 F1 hybrids
      were obtained with embryo rescue, when C. hispanica was used as the female
      parent. In the reciprocal cross (A x H), 232 hybrids were obtained without embryo
      rescue. From more than 1000 C. kralikii flowers pollinated with pollen grains of
      C. abyssinica (K x A), only 2 F1 hybrids were obtained with embryo rescue,
      whereas the reciprocal cross produced no hybrids, even with embryo rescue. The
      hybrids were confirmed at the morphological, cytological, and molecular levels.
      In the combinations of A x H and H x A, many BC1 hybrids were obtained without
      embryo rescue. In contrast, in the K x A cross, only 7 BC1 plants were obtained
      with embryo rescue, while no seed set was achieved under self-pollination or in
      backcrosses without embryo rescue. In the H x A F1 hybrids, the pollen
      stainability was 65.4-86.0%, with an average of 76.9%. In comparison, the pollen
      viability of hybrids in the reciprocal cross (A x H) ranged from 66.2 to 81.1%,
      with an average of 75.4%. Fertile pollen grains were not found in the K x A F1
      hybrids. All F1 hybrids of the 3 crosses (H x A, A x H, and K x A) had the
      expected 2n = 75 chromosomes. AFLP analyses indicated that all F1 hybrids and
      their progenies had typical bands of the parents. These hybrids and progenies are
      anticipated to be valuable for future C. abyssinica improvement in breeding
      programs.

PMID- 24737516
TI  - Diagnostic value of cytological and microbiological methods in cryptococcal
      meningitis.
AB  - The aim of this study was to investigate diagnostic methods for cryptococcal
      meningitis (CM). A retrospective analysis was conducted for 31 patients with CM
      confirmed by etiologic detection of cerebrospinal fluid in our hospital in the
      past 5 years. Nineteen cases in 31 patients were confirmed with CM in the first
      diagnosis, with a misdiagnosis rate of 38.7%. The positive rates of cryptococcus
      detection in cerebrospinal fluid with May-Grunwald-Giemsa (MGG)-, ink-, and
      Alcian blue-staining methods were 86.9, 70.9, and 80.6%, respectively. The
      misdiagnosis rate of CM is high during the early stage of disease. The total
      positive rate of cryptococcus diagnosis using the MGG-staining method was
      significantly higher than that using the ink-staining method. These results are
      important for diagnosing CM. 

PMID- 24737517
TI  - B chromosome prevalence and physical mapping of 18S rDNA and H4 histone sites in
      the grasshopper Xyleus discoideus angulatus (Romaleidae).
AB  - We sampled 11 natural populations of the grasshopper Xyleus discoideus angulatus
      in Northeastern Brazil to analyze B chromosome frequency and meiotic behavior. We
      observed a single large B chromosome, resembling the X chromosome, in 29 of the
      402 specimens. Eight of the 11 populations had B chromosomes, with a rather broad
      geographical distribution, suggesting that this is an ancient polymorphism;
      significant differences were observed in B chromosome prevalence among the
      populations. Presence of the B chromosome was associated with increased frequency
      of macrospermatids. Fluorescent in situ hybridization revealed 18S rDNA sites in
      the pericentromeric regions of the X and L3 chromosomes, although some
      populations had an additional locus on the M4 chromosome. No variation was found
      for chromosome location of H4 histone genes, which were always observed in
      paracentromeric regions of the L2, M4 and X chromosomes, a rather unusual
      location compared to locations known from the families Acrididae and
      Proscopiidae. These B chromosomes lacked these two kinds of repetitive DNA, at
      least in amounts that can be visualized by fluorescent in situ hybridization,
      suggesting that these B chromosomes did not originate from any of the four
      chromosomes carrying rDNA or H4 histone genes. 

PMID- 24737518
TI  - RNA-seq reveals the downregulated proteins related to photosynthesis in growth
      inhibited rice seedlings induced by low-energy N+ beam implantation.
AB  - Transcriptomic research based on RNA sequencing (RNA-seq) technology is
      innovative and will provide new opportunities and biological perspectives for the
      use of ion-beam implantation in plants. Using RNA-seq, transcriptomes of whole
      rice seedlings generated from seeds implanted with a low-energy N+ beam were
      analyzed 96 h after planting. We identified 544 transcripts that were
      differentially expressed genes (DEGs) in the non-growth-inhibited sample
      implanted by an N+ beam, including 262 upregulated transcripts and 282
      downregulated transcripts. Next, 776 transcripts were identified as DEGs in
      significantly damaged and growth-inhibited rice seedlings induced by N+ beam
      implantation, including 283 upregulated transcripts and 493 downregulated
      transcripts. The Gene Ontology (GO) analysis showed that 19 downregulated DEGs in
      the injured rice seedlings are enriched for the biological process GO term
      photosynthesis. The Kyoto Encyclopedia of Genes and Genomes pathway analysis also
      showed that 11 downregulated DEGs related to chlorophyll a/b-binding proteins are
      statistically significantly enriched in the photosynthesis-antenna protein
      pathway (Pathwayid: map00196). This result suggested that the downregulated and
      injured photosynthesis system contributed to the growth inhibition of rice
      seedlings induced by low-energy N+ beam implantation.

PMID- 24737519
TI  - Effects of polymorphisms in the XRCC1, XRCC3, and XPG genes on clinical outcomes
      of platinum-based chemotherapy for treatment of non-small cell lung cancer.
AB  - This study aimed to investigate the effects of single-nucleotide polymorphisms
      (SNPs) XRCC1 Arg194Trp, XRCC1 Arg280His, XRCC1 Arg399Gln, XRCC3 Thr241Met, XPG
      His104Asp, and XPG His46His in genes involved in the DNA-repair pathway on the
      outcomes of platinum-based chemotherapy in patients with advanced non-small cell
      lung cancer (NSCLC). The study period was from January 2005 to January 2006, and
      378 NSCLC patients were enrolled within 1 month after being diagnosed with NSCLC.
      Genomic DNA was extracted using the Qiagen Blood Kit. Polymerase chain reaction
      combined with a restriction fragment length polymorphism assay was used for
      genotyping. Individuals with the XRCC1 399A/A genotype had a higher probability
      of responding well to platinum-based chemotherapy, indicated by an odds ratio
      (OR) of 2.27 [95% confidence interval (CI)=1.64-6.97]. Similarly, the XPG T/T
      genotype was significantly associated with improved responses to chemotherapy,
      indicated by an OR of 1.90 (95%CI=1.10-3.28). The XRCC1 399A/A genotype was
      significantly associated with longer disease-free survival and overall survival,
      indicated by hazard ratios (HRs) of 0.48 (95%CI=0.25-0.88) and 0.51 (95%CI=0.26-
      0.98), respectively. Moreover, the XPG 46T/T genotype increased the likelihood of
      longer disease-free survival and overall survival of NSCLC patients treated with
      platinum-based chemotherapy (HR=0.47; 95%CI=0.22-0.82 and HR=0.52; 95%CI=0.31-
      0.96, respectively). These results indicate that XRCC1 Arg399Gln and XPG His46His
      might significantly affect the clinical outcomes of platinum-based chemotherapy,
      highlighting the need for larger studies to confirm the role of these two SNPs in
      outcomes of NSCLC treatments.

PMID- 24737520
TI  - Development of polymorphic microsatellite markers and the population genetic
      structure of the half-fin anchovy, Setipinna taty.
AB  - Microsatellite markers for the half-fin anchovy Setipinna taty were developed
      from the enriched (CA)15 genomic library, and they were used for the population
      genetic studies of the half-fin anchovy from Chinese coastal areas. Samples were
      collected from five localities of the East China Sea and the Yellow Sea. Eleven
      simple sequence repeat markers were used to assess genetic differentiation in 30
      individuals at each locality. As a result, 59 alleles were recorded over all loci
      with an average of 5.36 alleles per locus. Observed and expected heterozygosities
      ranged from 0.27 to 0.73 and 0.50 to 0.89, respectively. Analysis of molecular
      variation indicated that the variation within individuals was high (70.68%),
      while variations of individuals within and among populations were low (22.47 and
      6.85%). The phylogenetic tree showed that these populations could be divided into
      two clusters: populations of the East China Sea, which came from Ninghai,
      Xiangshan and Zhoushan, and populations of the Yellow Sea, which were from Yantai
      and Weihai. It revealed that significant geographic structure existed in this
      species. All of the results indicated that high genetic diversity existed in the
      half-fin anchovy from different geographic populations. This conclusion was
      consistent with the classification based on morphological and physiological
      characteristics. 

PMID- 24737521
TI  - Association of a transforming growth factor-beta1 polymorphism with acute
      coronary syndrome in a Chinese Han population.
AB  - Acute coronary syndrome (ACS) is a complex multifactorial and polygenic disorder
      that is thought to result from the interaction between an individual's genetic
      makeup and various environmental factors. The aim of this study was to
      investigate the association of a transforming growth factor-beta1 (TGF-beta1)
      polymorphism (-509C>T) with ACS in a Chinese Han population. The TGF-beta1
      polymorphism was evaluated in 336 patients with ACS and 396 healthy control
      subjects by polymerase chain reaction-restriction fragment length polymorphism.
      The genotype distributions of the control and ACS groups were in Hardy-Weinberg
      equilibrium (X(2) = 3.54 and X(2) = 1.72, respectively, P > 0.05). The
      frequencies of the CC, CT, and TT genotypes were 22.61, 53.57, and 20.83% in the
      ACS group, respectively, whereas they were 8.33, 48.74, and 42.17% in controls.
      There were significant differences between controls and ACS patients in the
      frequencies of the CC genotype and the C allele. These results suggest that the
      promoter polymorphism (-509C>T) in TGF-beta1 is associated with ACS in this
      population. The CC genotype and the C allele of TGF-beta1 might be a specific
      risk factor of ACS in the Chinese Han population in Xinjiang.

PMID- 24737522
TI  - Bombyx mori pylorus infection by Alphabaculovirus.
AB  - Alphabaculovirus is an entomopathogenic virus genus that infects Bombyx mori,
      which is known as the Bombyx mori multiple nucleopolyedrovirus (BmMNPV). This
      virus is polyorganotrophic, and a series of tissues are known as targets;
      however, there is currently no information regarding infection in the pylorus,
      the segment of the hindgut that is present in the midgut transition and is
      responsible for food passage control. Thus, in the present study, we aimed to
      analyze infection of the B. mori pylorus by BmMNPV. To do so, hybrid B. mori
      larvae were inoculated with a viral suspension of BmMNPV, and segments of the
      intestine containing the pylorus and its subdivisions, the posterior interstitial
      ring (PIR), pyloric cone, and pyloric valve, were dissected and processed for
      light microscopy on different days post inoculation. The results showed that B.
      mori pylorus subdivisions respond differently to infection, and the anterior area
      of the PIR is susceptible with these cells being the secondary infection targets.
      Cytological analysis revealed the presence of viroplasm in the hypertrophic
      nucleus, followed by the formation and development of viral polyhedra. Cytolysis
      occurred at the end of the infectious cycle, thereby releasing polyhedra and
      enabling the spread of the disease. There was no evidence of BmMNPV infection in
      the posterior area of the PIR, cone, or pyloric valve. These results will
      contribute to greater understanding of the virus infectious cycle, whose
      consequent epizootic disease can negatively impact this economically important
      insect that is used in silk production in Brazil.

PMID- 24737523
TI  - Association between rs11001553 of DKK1 and non-syndromic tooth agenesis in the
      Chinese Han population.
AB  - Tooth agenesis is one of the most common anomalies of human dentition. Recent
      genetic studies have provided information regarding a number of genes related to
      both syndromic and non-syndromic forms of hypodontia. In a previous study, we
      found that polymorphism in rs11001553 of DKK1 was associated with hypodontia in
      the Chinese Han population. In this study, we extended this investigation to 89
      individuals diagnosed with sporadic non-syndromic oligodontia (40 males and 49
      females). These individuals were analyzed with 268 subjects (123 males and 145
      females) diagnosed with non-syndromic hypodontia and 190 healthy control subjects
      (99 males and 91 females). DNA was obtained from whole blood or saliva samples
      and genotyping was performed by matrix-assisted laser desorption ionization-time
      of flight mass spectrometry. Significant differences were observed in the allele
      and genotype frequencies of rs11001553 of DKK1. These data demonstrated an
      association between rs11001553 of DKK1, a tooth development-associated gene, and
      non-syndromic tooth agenesis in Chinese Han individuals. This information may
      provide further understanding of the molecular mechanisms of tooth agenesis.
      Furthermore, DKK1 can be regarded as a marker gene for the risk of tooth
      agenesis. 

PMID- 24737525
TI  - Torsional and cyclic fatigue resistances of glide path preparation instruments: G
      file and PathFile.
AB  - This study aimed to compare cyclic fatigue and torsional resistances of glide
      path creating instruments with different tapers and tip sizes. Two sizes (G1 and
      G2) from G-File system and three sizes (PathFile #1, #2, and #3) from PathFile
      system were used for torsional resistance and cyclic fatigue resistance tests (n
      = 10). The torsional resistance was evaluated at 2-, 3-, 4-, 5-, and 6-mm from
      the file tip by plotting the torsional load changes until fracture by rotational
      loading of 2 rpm. The cyclic fatigue resistance was compared by measuring the
      number of cycles to failure. Data were analyzed statistically using one-way ANOVA
      and Duncan's post-hoc comparison. The length of the fractured file fragment was
      also measured. All fractured fragments were observed under a scanning electron
      microscope (SEM). Although G-2 file showed a lower torsional strength than
      PathFile #3 at 2- and 3-mm levels (p < 0.05), they had similar ultimate strengths
      at 4-, 5-, and 6-mm levels (p > 0.05). The smaller files of each brand had a
      significantly higher cyclic fatigue resistance than the bigger ones (p < 0.05).
      PathFile #1 and #2 had higher fatigue resistances than G-files (p < 0.05). While
      G-1 had a similar fatigue resistance as PathFile #3, G-2 showed the lowest and
      PathFile #1 showed the highest resistances among the tested groups (p < 0.05).
      The SEM examination showed typical appearances of cyclic fatigue and torsional
      fractures, regardless of the tested levels. Clinicians may consider the
      instruments' sizes for each clinical case in order to get efficient glide path
      with minimal risk of fracture.

PMID- 24737524
TI  - Identification and quantitation of phenolic compounds from the seed and pomace of
      Perilla frutescens using HPLC/PDA and HPLC-ESI/QTOF/MS/MS.
AB  - INTRODUCTION: Perilla frutescens (L.) Britt., an essential traditional Asian crop
      and Chinese medicine, potentially exerts anti-oxidation effects through its
      phenolic compounds. These compounds have already been reported in perilla seed,
      however, little is reported in Perilla pomace, the primary waste during oil
      production of Perilla seed. OBJECTIVE: To investigate major phenolic compounds in
      perilla seeds and pomaces in order to check whether the pomace could be an
      alternative resource to the seed for nutritional and medical purposes. METHODS:
      Compounds in extracts of perilla seeds and pomaces were separated by high
      performance liquid chromatography and detected by photodiode array, and by
      electrospray ionisation with quadrupole time-of-flight tandem mass spectrometry.
      Herb-markers selected by principal components analysis were then quantified in
      both seeds and pomaces. Moreover, a fingerprinting approach and multiple
      discriminant analysis were applied to screen the phenolic markers in 22 samples.
      RESULTS: Ten phenols were tentatively identified, among which four (rosmarinic
      acid, luteolin, apigenin and rosmarinic acid-3-O-glucoside) were selected as herb
      markers. Perilla seeds and pomaces showed similar phenol profiles, however, the
      pomaces contained almost two times the amount of the four herb-markers than the
      seeds. CONCLUSION: The results indicated perilla pomace is a promising
      alternative source of phenolic compounds that could be recovered and potentially
      used as natural anti-oxidants.

PMID- 24737526
TI  - Post-approval appending of CSARs to drug package inserts: an analysis of the
      types of adverse reactions and time to addition.
AB  - PURPOSE: The aim of this study was to quantitatively analyze clinically
      significant adverse reactions (CSARs) added to drug package inserts after
      approval and to investigate the time to these post-approval additions as an
      indicator of safety-related regulatory actions. METHODS: Drugs containing new
      active ingredients that had been approved in Japan from April 2001 to December
      2010 were analyzed. We examined CSARs that had been reported in the first version
      of the package inserts and subsequent additions through notifications from
      Japan's Ministry of Health, Labour and Welfare until the end of 2011. Relative
      risks (RRs) for post-approval addition of CSARs were calculated for various
      categories of disorders. The median lengths of time to post-approval addition of
      CSARs were compared. RESULTS: A total of 238 drugs were examined. Of the 2487
      CSARs associated with these drugs, 737 had been added after approval. The
      analysis revealed a higher likelihood for post-approval addition of CSARs for
      "Hepatobiliary disorders" (RR: 1.41; 95% confidence interval [CI]: 1.19-1.68),
      "Gastrointestinal disorders" (RR: 1.35; 95%CI: 1.10-1.66), and "Musculoskeletal
      and connective tissue disorders" (RR: 1.52; 95%CI: 1.11-2.07). In contrast,
      "Cardiac disorders" showed reduced likelihood in comparison with other disorders.
      For the time until post-approval addition of CSARs, "Skin and subcutaneous tissue
      disorders" showed the longest durations, with a median of 3020 days. CONCLUSIONS:
      Our quantitative analysis suggests that some CSARs were added more frequently to
      package inserts after approval and that time to post-approval additions of CSARs
      varied with the types of adverse drug reactions. These results can support the
      coherent implementation of pharmacovigilance activities.

PMID- 24737527
TI  - In memoriam...George J. Hill, M.D., Ph.D.

PMID- 24737528
TI  - Assembly of a nanoreactor system with confined magnetite core and shell for
      enhanced Fenton-like catalysis.
AB  - Conventional solid catalysts for heterogeneous Fenton-like reactions in bulk
      solution usually suffer from aggregation and vulnerability, which greatly lower
      the catalytic efficiency and hamper their practical application. Herein, we
      demonstrate a promising yolk-shell nanostructure with both the core and the shell
      composed of magnetite (designated as yolk-like Fe3O4@Fe3O4/C) as a nanoreactor
      capable of accommodating the Fenton-like reaction into its void space. Benefiting
      from the mesoporous shell and perfect interior cavity of this composite,
      reactants can access and be abundantly confined within the microenvironment where
      Fe3O4 sites are dispersed on the entire cavity surfaces, thus leading to a higher
      catalytic efficiency compared with the conventional solid catalysts in bulk
      solution. The chosen model reaction of chlorophenols degradation in the presence
      of the as-prepared materials as well as hydrogen peroxide (H2O2) confirms this
      assumption. Under the optimal reaction conditions, more than 97 % 4-chlorophenol
      (4-CP) can be degraded in the Fe3O4@Fe3O4/C nanoreactor, whereas only 28 % can be
      achieved by using bare Fe3O4 particles within 60 min. Furthermore, owing to the
      existence of the outermost carbon layer and high-magnetization properties, the
      nanoreactor can be re-used for several runs. The synthesized nanoreactor displays
      superior catalytic activity toward the Fenton-like reaction compared with the
      bare solid catalysts, and thereby holds significant potential for practical
      application in environmental remediation.

PMID- 24737529
TI  - Clinical value of magnetic resonance imaging in patients with Mayer-Rokitansky
      Kuster-Hauser (MRKH) syndrome: diagnosis of associated malformations, uterine
      rudiments and intrauterine endometrium.
AB  - OBJECTIVES: The aim of this study was to evaluate the accuracy of preoperative
      magnetic resonance imaging (MRI) in the diagnosis of malformations associated
      with Mayer-Rokitansky-Kuster-Hauser (MRKH) syndrome and identification of uterine
      endometrium to optimise the clinical management. METHODS: We retrospectively
      reviewed 214 consecutive MRKH patients, mean age 19 years, who underwent
      laparoscopy-assisted neovagina creation. A total of 115 patients (53.7%) met the
      inclusion criterion of sufficient preoperative MRI. In 110 of them (95.7%), MRI
      findings were correlated with laparoscopy and associated malformations. In 39
      cases (35.5%) uterine rudiments were removed and analysed histopathologically.
      RESULTS: Ten per cent (11/110) of the patients showed complete uterine agenesis.
      The others presented with either unilateral (n = 16; 14.5%) or bilateral (n = 83;
      75.5%) uterine rudiments. MRI detection of uterine rudiments agreed in 78.2%
      (86/110) with laparoscopy. In 85.4% of the removed rudiments, MRI could correctly
      diagnose the existence of the endometrium. Compared to laparoscopy, MRI could
      exactly detect ovaries in 97.3% (107/110). Renal or ureteral malformations were
      seen in 32 cases (27.8%). In 83% of unilateral renal agenesis and unilateral
      rudiment, the latter was located at the side of the kidney. CONCLUSIONS: MRI is
      useful for preoperative detection of MRKH-associated malformations and assessment
      of the endometrium to further optimise MRKH patient treatment. KEY POINTS: *
      Pelvic MRI is useful for preoperative detection of MRKH-associated malformations.
      * MRI can diagnose uterine endometrium in MRKH patients with high precision. *
      Preoperative MRI can optimise clinical management of patients with MRKH syndrome.

PMID- 24737530
TI  - Feasibility of prospectively ECG-triggered high-pitch coronary CT angiography
      with 30 mL iodinated contrast agent at 70 kVp: initial experience.
AB  - OBJECTIVES: To evaluate the feasibility, image quality and radiation dose of
      prospectively ECG-triggered high-pitch coronary CT angiography (CCTA) with 30 mL
      contrast agent at 70 kVp. METHODS: Fifty-eight patients with suspected coronary
      artery disease, a body mass index (BMI) of less than 25 kg/m(2), sinus rhythm and
      a heart rate (HR) of less than 70 beats per minute (bpm) were prospectively
      enrolled in this study. Thirty mL of 370 mg I/mL iodinated contrast agent was
      administrated at a flow rate of 5 mL/s. All patients underwent prospectively ECG
      triggered high-pitch CCTA on a second-generation dual-source CT system at 70 kVp
      using automated tube current modulation. RESULTS: Fifty-six patients (96.6%) had
      diagnostic CCTA images and two patients (3.4%) had one vessel with poor image
      quality each rated as non-diagnostic. No significant effects of HR, HR
      variability and BMI on CCTA image quality were observed (all P > 0.05). Effective
      dose was 0.17 +/- 0.02 mSv and the size-specific dose estimate was 1.03 +/- 0.13
      mGy. CONCLUSION: Prospectively ECG-triggered high-pitch CCTA at 70 kVp with 30 mL
      of contrast agent can provide diagnostic image quality at a radiation dose of
      less than 0.2 mSv in patients with a BMI of less than 25 kg/m(2) and an HR of
      less than 70 bpm. KEY POINTS: * Prospectively ECG-triggered high-pitch CCTA at 70
      kVp/30 mL contrast agent is feasible. * Diagnostic image quality can be obtained
      at a radiation dose of less than 0.2 mSv. * This protocol is suitable for normal
      weight patients with slow heart rate.

PMID- 24737531
TI  - Novel technique for identification of ureters using sodium fluorescein.
AB  - BACKGROUND: The unique property of sodium fluorescein has made it ideal for use
      in medical applications such as diagnostic ophthalmology and intravenous
      angiography. It is mainly excreted via the renal system and although extensively
      used in these diagnostic applications, it has not been widely used to aid in the
      visualization of the ureters. It is possible to visualize the urinary tract by
      shining a source of light and studying the fluorescence using a special filter.
      The goal of our study was to assess the real-time visualization of ureters using
      intravenous sodium fluorescein under the stimulus of a 530 nm wavelength light.
      MATERIALS AND METHODS: Nine 250 gm Wister rats were given an intravenous dose of
      0.01 ml of sodium fluorescein. A laparotomy was immediately performed following
      the administration of dye. Anesthesia was performed with an intraperitoneal dose
      of ketamine-xylazine. The retroperitoneum was exposed and observed under an
      alternating white xenon and a 530 nm excitation light with an objective to
      visualize the organs captured within the fluorescence of the compound (sodium
      fluorescein). RESULTS: Under xenon light, the location of the kidneys and urinary
      bladder were visualized, but not the ureters. The light was then changed to a 530
      nm wavelength mode when the location and orientation of the ureters was
      visualized along with the peristaltic movements. Fluorescence visualization of
      the ureters was noted 5-10 min following kidney visualization. In addition, the
      vascular structures in close proximity to the ureters were also visualized. None
      of the rats underwent any retroperitoneal dissection, and in one case, partial
      mobilization of a kidney was undertaken. All rats were euthanized at the
      completion of the procedure. CONCLUSION: Intravenous administration of sodium
      fluorescein enables fluorescence visualization of the ureters in a rat model,
      after activation with a 530 nm light transmitter.

PMID- 24737532
TI  - Laparoscopic transperitoneal anterior adrenalectomy in pheochromocytoma:
      experience in 62 patients.
AB  - BACKGROUND: Aim was to evaluate the results in 62 patients undergoing
      laparoscopic adrenalectomy (LA) for the treatment of pheochromocytoma (PHE), with
      a transperitoneal anterior approach for lesions on the right side, and with a
      transperitoneal anterior submesocolic approach in case of left-sided lesions.
      METHODS: Sixty-two patients underwent LA for the treatment of PHE at two centers
      in Rome and Ancona (Italy). Two patients had bilateral lesions, for a total of 64
      adrenalectomies. Sporadic PHE occurred in 57 patients (91.9 %) and in 5 (8.0 %)
      it was familiar. Thirty-six patients (58.0 %) underwent right adrenalectomy, 24
      (38.7 %) left adrenalectomy, and in 2 cases (3.2 %) LA was bilateral. In 38 cases
      of right adrenalectomy (59.3 %) and in 5 cases of left adrenalectomy (7.8 %), the
      approach was a transperitoneal anterior one. A transperitoneal anterior
      submesocolic approach was used in 21 left adrenalectomy cases (32.8 %). RESULTS:
      Mean operative time for right and left transperitoneal anterior LA was 101 min
      (range 50-240) and 163 min (range 50-190), respectively. Mean operative time for
      left transperitoneal anterior submesocolic LA was 92 min (range 50-195). For
      bilateral adrenalectomy, mean operative time was 210 min (range 200-220).
      Conversion to open surgery occurred in 2 cases (3.22 %) due to extensive
      adhesions (1) and hemorrhage (1). One major and three minor complications were
      observed. Mobilization occurred on the first postoperative day. Hospitalization
      was 4.8 days (range 2-19). The lesions had a mean diameter of 4.5 cm (range 0.5
      10). CONCLUSIONS: Early identification with no gland manipulation prior to
      closure of the adrenal vein is the main advantages of the transperitoneal
      anterior approach. PHE may be treated safely and effectively by a laparoscopic
      transperitoneal anterior approach for right-sided lesions and with a
      transperitoneal anterior submesocolic approach for left-sided ones.

PMID- 24737533
TI  - A minimally invasive strategy for Mirizzi syndrome: the combined endoscopic and
      robotic approach.
AB  - BACKGROUND: Mirizzi syndrome (MS) is a rare complication of gallstone disease.
      Despite the fact that successful laparoscopic treatments have been reported, open
      surgery remains the gold standard approach for this disease due to technical
      difficulties involved. METHODS: A minimally invasive strategy combining
      endoscopic retrograde cholangiopancreatography (ERCP) and robotic surgery for the
      management of MS was implemented in early 2012. This consisted of a preoperative
      ERCP for definitive diagnosis and endoscopic stent insertion. Robotic surgical
      approach was used during operation to facilitate gall bladder removal and suture
      of defect over common duct. ERCP was repeated postoperatively for stent removal.
      Patient demographics and treatment outcomes were collected prospectively. A
      historical cohort of patients with MS who underwent conventional surgery between
      1999 and 2011 was identified for comparison of treatment outcomes. RESULTS: Five
      patients with MS were managed with this strategy. Robotic subtotal
      cholecystectomy was successfully performed in all the patients without conversion
      or morbidity. When compared with a historical cohort of 17 patients who underwent
      surgery for MS, this group of patients had significantly less conversion and
      shorter hospital stay though the operation time was longer. It also showed less
      blood loss and less postoperative complications but these were not statistically
      significant. CONCLUSION: Mirizzi syndrome can be effectively managed with a
      minimally invasive approach by adopting a robot-assisted surgery together with a
      planned pre- and postoperative ERCP.

PMID- 24737534
TI  - The effect of underlying liver disease on short-term outcomes following bariatric
      surgery.
AB  - BACKGROUND: Morbid obesity is strongly associated with nonalcoholic fatty liver
      disease. However, the effect of underlying liver disease on clinical outcomes
      following bariatric surgery has not been well studied. This study aims to
      determine the effect of underlying liver disease on short-term outcomes in
      bariatric patients using the model of end-stage liver disease (MELD) scoring
      system as a practical measure of hepatic dysfunction. METHODS: A retrospective
      cohort analysis was performed using data from the American College of Surgeons'
      National surgery quality improvement program participant use files. The study
      population consisted of patients that underwent elective laparoscopic-stapled
      bariatric surgery for morbid obesity between 2005 and 2012. Patients were
      excluded if they had a bleeding disorder or renal failure requiring dialysis. The
      optimal MELD cut-off score to predict 30-day adverse events was determined and
      used to stratify patients into two groups. The primary outcome was 30-day adverse
      events, defined as a postoperative complication or reoperation. The secondary
      outcome was 30-day mortality. A multiple logistic regression was performed to
      adjust the odds ratio (OR) estimate for 30-day adverse events based on the MELD
      cut-off score. RESULTS: 38,875 patients were included in the study population. A
      MELD score of 7.9 was determined to be the optimal cut-off to predict 30-day
      adverse events based on the maximized linear combination of specificity and
      sensitivity. After adjusting for confounding, the OR estimates for 30-day adverse
      events and mortality using the cut-off score as the key predictor were 1.22 [95 %
      CI 1.06-1.41] and 2.33 [95 % CI 1.19-4.56], respectively. CONCLUSIONS: Using this
      large national surgical registry, bariatric patients with MELD scores >=7.9 had a
      significant but marginal risk of 30-day adverse events and mortality. This
      suggests that severity of liver disease may affect bariatric surgery outcomes and
      should be considered during preoperative evaluations.

PMID- 24737535
TI  - Cognitive predictors of medical decision-making capacity in mild cognitive
      impairment and Alzheimer's disease.
AB  - OBJECTIVE: Impaired capacity to make decisions in everyday life and situations of
      medical treatment is an inevitable consequence of the cognitive decline in
      Alzheimer's disease (AD). The objective of this study was to identify the most
      powerful cognitive component(s) that best predicted medical decision-making
      capacity (MDMC) in patients with AD and mild cognitive impairment. METHOD: Three
      groups of subjects participated in the study: patients with AD (n = 20), mild
      cognitive impairment (n = 21), and healthy control subjects (n = 33). MDMC was
      assessed by the linguistic instrument for medical decision-making (LIMD) and
      related to demographics and 27 cognitive test measures. RESULTS: The cognitive
      tests were found to aggregate into four components using a principle component
      analysis. The four components, which correspond to verbal knowledge, episodic
      memory, cognitive speed, and working memory, accounted for 73% of the variance in
      LIMD according to a stepwise regression analysis. Verbal knowledge was the most
      powerful predictor of LIMD (beta = 0.66) followed by episodic memory (beta =
      0.43), cognitive speed (beta = 0.32), and working memory (beta = 0.23). The best
      single test as shown by the highest correlation with LIMD was Reading speed (R =
      0.77). CONCLUSION: Multiple factors are involved in MDMC in subjects with
      cognitive impairment. The component of verbal knowledge was the best predictor of
      MDMC and Reading speed was the most important single cognitive test measurement,
      which assessed both rapid Reading and understanding of text.

PMID- 24737536
TI  - Computer simulation of dental professionals as a moral community.
AB  - Current empirical studies of moral behavior of healthcare professionals are
      almost entirely focused on self-reports, usually collected under the assumption
      that an ethical disposition characterizes individuals across various contexts. It
      is well known, however, that individuals adjust their behavior to what they see
      being done by those in their peer group. That presents a methodological challenge
      to traditional research within a community of peers because the behavior of each
      individual is both the result of norms and a contributor to the norms of others.
      Computer simulations can be used to address this methodological challenge. A
      Markov replicator model that runs on an Excel spreadsheet was used to investigate
      a community with four agent types in the dental community: devious practitioners,
      ethical practitioners who avoid involvement in the poor ethics of others, ethical
      practitioners who accept it as part of their professional responsibility to
      challenge colleagues who act unprofessionally, and those who enforce ethical
      standards. A panel of leaders in the profession independently estimated
      parameters for the model and criteria for a possible distribution of agent types
      in the community. The simulation converged on distributions of the agent types
      that were very similar to the expectations of the panel. The simulation suggests
      the following characteristics of such moral communities: The structure of such
      communities is robust across a wide distribution. It appears that reduction in
      unethical behavior is more sensitive to the way ethical practitioners interact
      with each other than to sanctions the enforcement community imposes on unethical
      practitioners, and that large external interventions will be short lived. 

PMID- 24737537
TI  - Alzheimer, dementia and the living will: a proposal.
AB  - The world population aged significantly over the twentieth century, leading to an
      increase in the number of individuals presenting progressive, incapacitating,
      incurable chronic-degenerative diseases. Advances in medicine to prolong life
      prompted the establishment of instruments to ensure their self-determination,
      namely the living will, which allows for an informed person to refuse a type of
      treatment considered unacceptable according to their set of values. From the
      knowledge on the progression of Alzheimer disease, it is possible to plan the
      medical care, even though there is still no treatment available. Irreversible
      cognitive incapacity underlines the unrelenting loss of autonomy of the demented
      individual. Such a loss requires the provision of specific and permanent care.
      Major ethical issues are at stake in the physician-patient-family relationship,
      even when dementia is still at an early stage. The authors suggest that for an
      adequate health care planning in Alzheimer disease the living will can be
      presented to the patient in the early days of their geriatric care, as soon as
      the clinical, metabolic or even genetic diagnosis is accomplished. They also
      suggest that the appointment of a health care proxy should be done when the
      person is still in full enjoyment of his cognitive ability, and that the
      existence and scope of advance directives should be conveyed to any patient in
      the early stages of the disease. It follows that ethical guidelines should exist
      so that neurologists as well as other physicians that deal with these patients
      should discuss these issues as soon as possible after a diagnosis is reached. 

PMID- 24737538
TI  - Men's health big data.

PMID- 24737539
TI  - Silencing the radicals improves Click Chemistry.
AB  - Modern fluorescence imaging microscopy in living and fixed material makes use of
      fluorescent probes to label targeted entities. Common labelling approaches
      include classical immunocytochemistry, expression of chimerically tagged
      fluorescent protein domains, and chemical affinity-binding or covalent labelling.
      Of these methods, the so-called "Click Chemistry", is emerging as one of the most
      influential labelling chemistries introduced in recent times, offering enormous
      utility for bio-orthoganol attachment of fluorescent probes to biological target
      entities. In this issue of Biotechnology Journal, Loschberger, Niehorster and
      Sauer report "ClickOx", a Click Chemistry protocol that uses an enzymatic oxygen
      scavenger system to reduce concurrent ROS-associated damage during Click
      labeling.

PMID- 24737540
TI  - Hypofractionation with simultaneous integrated boost for early breast cancer:
      results of the German multicenter phase II trial (ARO-2010-01).
AB  - PURPOSE: To evaluate the feasibility of hypofractionation with SIB in all
      settings in Germany to prepare a multicenter treatment comparison. METHODS:
      Eligible patients had histopathologically confirmed breast cancer operated by
      BCS. Patients received WBI 40.0 Gy in 16 fractions of 2.5 Gy. A SIB with 0.5 Gy
      per fraction was administered to the tumor bed, thereby giving 48.0 Gy in 16
      fractions to the boost-PTV sparing heart, LAD, lung, contralateral breast. The
      primary study objective was feasibility, administration of specified dose in 16
      fractions within 22-29 days with adherence to certain dose constraints (heart;
      LAD; contralateral breast); secondary endpoints were toxicity, QoL. RESULTS: 151
      patients were recruited from 7 institutions between 07/11-10/12. 10 patients met
      exclusion criteria prior to irradiation. All but two patients (99%) received the
      prescribed dose in the PTVs. Adherence to dose constraints and time limits was
      achieved in 89% (95% CI 82% to 93%). 11 AE were reported in 10 patients; five
      related to concurrent endocrine therapy. Two of the AEs were related to
      radiotherapy: grade 3 hot flushes in two cases. QoL remained unchanged.
      CONCLUSION: Hypofractionation with a SIB is feasible and was well tolerated in
      this study.

PMID- 24737541
TI  - Cisplatin- vs. oxaliplatin-based radiosensitizing chemotherapy for squamous cell
      carcinoma of the esophagus: a comparison of two preoperative radiochemotherapy
      regimens.
AB  - PURPOSE: To compare the outcomes of two neoadjuvant radiochemotherapy (N-RCT)
      regimens for squamous cell carcinoma of the esophagus (ESCC). METHODS: The
      standard N-RCT regimen for ESCC at our institution between 2002 and 2011 was a
      total dose of 45 Gy (1.8-Gy fractions) with concomitant cisplatin (20 mg/m(2),
      days 1-5 and 29-33) and 5-fluorouracil (5-FU; 225 mg/m(2), 24 h continuous
      infusion on days 1-33). During the same period, a phase I/II study comparing the
      standard ESCC N-RCT protocol with a regimen identical except for the replacement
      of cisplatin with weekly oxaliplatin (40-50 mg/m(2)) was performed at our center.
      The standard regimen was used to treat 40 patients; 37 received the oxaliplatin
      regimen. All patients subsequently underwent radical resection with
      reconstruction according to tumor location and two-field lymph node dissection.
      RESULTS: Median follow-up time from the start of N-RCT was 74 months (range 3-116
      months). The two patient groups were comparable in terms of demographic and
      baseline tumor characteristics. R0 resection was achieved in 37/39 patients (95
      %) in the cisplatin-based N-RCT group, compared to 24/37 (65 %) in the
      oxaliplatin-based group (p = 0.002). A pathological complete response (pCR) was
      seen in the resection specimens from 18/39 patients (46 %) in the cisplatin-based
      N-RCT group and in 8/37 (22 %) oxaliplatin-group patients. In the cisplatin
      group, 2- and 5-year overall survival (OS) rates were 67 +/- 8 % and 60 +/- 8 %,
      respectively (median OS 103 months), compared to 38 +/- 8 % and 32 +/- 8 %,
      respectively, for the oxaliplatin group (median OS 17 months; hazard ratio, HR
      0.452; 95 % confidence interval, CI 0.244-0.839; p = 0.012). CONCLUSION:
      Oxaliplatin-based N-RCT resulted in poorer outcomes in ESCC patients and should
      not routinely replace cisplatin-based N-RCT.

PMID- 24737542
TI  - Gisele Guilbaud (1936-2013).

PMID- 24737543
TI  - Exploring changes in the brain associated with recovery from phantom limb pain-
      the potential importance of telescoping.

PMID- 24737544
TI  - Authors' reply to the comment by Harvie and Moseley.

PMID- 24737545
TI  - Dense energetic nitraminofurazanes.
AB  - 3,3'-Diamino-4,4'-bifurazane (1), 3,3'-diaminoazo-4,4'-furazane (2), and 3,3'
      diaminoazoxy-4,4'-furazane (3) were nitrated in 100 % HNO3 to give corresponding
      3,3'-dinitramino-4,4'-bifurazane (4), 3,3'-dinitramino-4,4'-azofurazane (5) and
      3,3'-dinitramino-4,4'-azoxyfurazane (6), respectively. The neutral compounds show
      very imposing explosive performance but possess lower thermal stability and
      higher sensitivity than hexogen (RDX). More than 40 nitrogen-rich compounds and
      metal salts were prepared. Most compounds were characterized by low-temperature X
      ray diffraction, all of them by infrared and Raman spectroscopy, multinuclear NMR
      spectroscopy, elemental analysis, and by differential scanning calorimetry (DSC).
      Calculated energetic performances using the EXPLO5 code based on calculated (CBS
      4M) heats of formation and X-ray densities support the high energetic
      performances of the nitraminofurazanes as energetic materials. The sensitivities
      towards impact, friction, and electrostatic discharge were also explored.
      Additionally the general toxicity of the anions against vibrio fischeri,
      representative for an aquatic microorganism, was determined. 

PMID- 24737546
TI  - Colorectal cancer screening in high-risk groups is increasing, although current
      smokers fall behind.
AB  - BACKGROUND: There is limited information about colorectal cancer (CRC) screening
      trends in high-risk groups, including the black, obese, diabetic, and smoking
      populations. For this study, the authors evaluated national CRC screening trends
      in these high-risk groups to provide insights into whether screening resources
      are being appropriately used. METHODS: This was a nationally representative,
      population-based study using the Behavioral Risk Factor Surveillance System from
      the Centers for Disease Control. Data analysis was performed using bivariate
      analyses with weighted logistic regression. RESULTS: In the general population,
      CRC screening increased significantly from 59% to 65% during the years 2006 to
      2010. The screening prevalence in non-Hispanic blacks was 58% in 2006 and 65% in
      2010. Among obese individuals, the prevalence of up-to-date CRC screening
      increased significantly from 59% in 2006 to 66% in 2010. Screening prevalence in
      individuals with diabetes was 63% in 2006 and 69% in 2010. The CRC screening
      prevalence in current smokers was 45% in 2006 and 50% in 2010. The odds of CRC
      screening in the non-Hispanic black population, the obese population, and the
      diabetic population were higher than in non-Hispanic whites, normal weight
      individuals, and the population without diabetes, respectively. Current smokers
      had significantly lower odds of CRC screening than never-smokers in the years
      studied (2006: odds ratio [OR], 0.71; 95% confidence interval [CI], 0.66-0.76;
      2008: OR, 0.67; 95% CI, 0.63-0.71; 2010: OR, 0.69; 95% CI, 0.66-0.73).
      CONCLUSIONS: The prevalence of CRC screening in high-risk groups is trending
      upward. Despite this, current smokers have significantly lower odds of CRC
      screening compared with the general population.

PMID- 24737548
TI  - U.S. Food and Drug Administration inspections of clinical investigators: overview
      of results from 1977 to 2009.
AB  - The U.S. Food and Drug Administration (FDA) Center for Drug Evaluation and
      Research is responsible for evaluating drug safety and efficacy, including
      oversight of clinical trials and principal investigators. The FDA Clinical
      Investigator Inspection List (CIIL) contains online, detailed, relevant
      information of all FDA inspections. We reviewed FDA inspections of clinical
      investigators to ascertain their outcome and included all inspections on the list
      (July 1977 through December 31, 2009; n = 9,481 inspections). Eighty-eight
      percent of inspections were "data audit" (primary purpose = verification of
      data), and the rest (12%) were "for cause." The number of inspections each year
      significantly increased over time (P < 0.0001) and averaged 350 per year in the
      past decade. No deficiencies were found in only 11.2% of all "data audit" and 5%
      of all "for cause" inspections. Only 31% of inspections resulted in "no action
      indicated." About two thirds of inspections resulted in some finding, requiring
      either voluntary investigator action (61.3% of inspections) or official FDA
      action (3.9%). The most frequently cited deficiencies were failure to follow
      investigational plan (34%), inadequate informed consent form (28%), and
      inadequate/inaccurate records (27%). In conclusion, over the past decade, the FDA
      has performed approximately 350 inspections per year, with the number increasing
      over time. The vast majority of FDA inspections yield deficiency findings and, as
      a result, only about one third of inspections have an outcome of "no action
      indicated."

PMID- 24737547
TI  - GM-CSF Production by Tumor Cells Is Associated with Improved Survival in
      Colorectal Cancer.
AB  - PURPOSE: Colorectal cancer infiltration by CD16(+) myeloid cells correlates with
      improved prognosis. We addressed mechanistic clues and gene and protein
      expression of cytokines potentially associated with macrophage polarization.
      EXPERIMENTAL DESIGN: GM-CSF or M-CSF-stimulated peripheral blood CD14(+) cells
      from healthy donors were cocultured with colorectal cancer cells. Tumor cell
      proliferation was assessed by (3)H-thymidine incorporation. Expression of
      cytokine genes in colorectal cancer and autologous healthy mucosa was tested by
      quantitative, real-time PCR. A tumor microarray (TMA) including >1,200 colorectal
      cancer specimens was stained with GM-CSF- and M-CSF-specific antibodies.
      Clinicopathological features and overall survival were analyzed. RESULTS: GM-CSF
      induced CD16 expression in 66% +/- 8% of monocytes, as compared with 28% +/- 1%
      in cells stimulated by M-CSF (P = 0.011). GM-CSF but not M-CSF-stimulated
      macrophages significantly (P < 0.02) inhibited colorectal cancer cell
      proliferation. GM-CSF gene was expressed to significantly (n = 45, P < 0.0001)
      higher extents in colorectal cancer than in healthy mucosa, whereas M-CSF gene
      expression was similar in healthy mucosa and colorectal cancer. Accordingly,
      IL1beta and IL23 genes, typically expressed by M1 macrophages, were expressed to
      significantly (P < 0.001) higher extents in colorectal cancer than in healthy
      mucosa. TMA staining revealed that GM-CSF production by tumor cells is associated
      with lower T stage (P = 0.02), "pushing" growth pattern (P = 0.004) and
      significantly (P = 0.0002) longer survival in mismatch-repair proficient
      colorectal cancer. Favorable prognostic effect of GM-CSF production by colorectal
      cancer cells was confirmed by multivariate analysis and was independent from
      CD16(+) and CD8(+) cell colorectal cancer infiltration. M-CSF expression had no
      significant prognostic relevance. CONCLUSIONS: GM-CSF production by tumor cells
      is an independent favorable prognostic factor in colorectal cancer.

PMID- 24737549
TI  - Genetic variations associated with postoperative recurrence in stage I non-small
      cell lung cancer.
AB  - PURPOSE: Postoperative recurrence in stage I non-small cell lung cancer (NSCLC)
      is the major cause of a poor prognosis. This study aims to identify genetic
      variants that are associated with the prognosis of early-stage NSCLCs.
      EXPERIMENTAL DESIGN: A genome-wide association study (GWAS) was conducted in 250
      patients in stage I NSCLCs and the results were replicated in additional 308
      patients. RESULTS: Results from an Affymetrix Genome-wide Human SNP array in 250
      patients identified 94 SNPs with significant associations (P < 2 * 10(-4)), which
      were selected for replication in 308 additional patients. Pooled analysis of the
      558 patients determined that rs1454694 in chromosome 4q34 was the most
      significant marker of lung cancer prognosis in the stage I patients (adjusted HR
      = 2.81; P = 5.91 * 10(-8)). After the candidate loci were mapped, an additional
      four markers at chromosome 4q34.3 were significantly associated with recurrence
      free survival (RFS; P < 5 * 10(-5)). A haplotype of five SNPs in 4q34 also showed
      significant association with RFS (P = 4.29 * 10(-6)). CONCLUSIONS: A genetic
      polymorphism rs1454694 was identified as a novel genetic risk factor for RFS of
      stage I NSCLCs. This genome-wide study suggests that genetic markers in 4q34.3
      contribute to predict the prognosis of Korean patients with stage I NSCLCs.

PMID- 24737550
TI  - Changes in nerve- and endothelium-mediated contractile tone of the corpus
      cavernosum in a mouse model of pre-mature ageing.
AB  - Erectile dysfunction (ED) is very prevalent in the older population, although the
      ageing-related mechanisms involved in the development of ED are poorly
      understood. We propose that age-induced differences in nerve- and endothelium
      mediated smooth muscle contractility in the corpus cavernosum (CC) could be found
      between a senescent-accelerated mouse prone (SAMP8) and senescent-accelerated
      mouse resistant (SAMR1) strains. We analysed the changes in muscle tension
      induced by electrical field stimulation (EFS) or agonist addition 'in vitro',
      assessing nerve density (adrenergic, cholinergic and nitrergic), the expression
      of endothelial nitric oxide synthase (eNOS), cGMP accumulation and the
      distribution of interstitial cells (ICs) by immunofluorescence. We observed no
      change in both the nerve-dependent adrenergic excitatory contractility at
      physiological levels of stimulation and in the nitrergic inhibitory response in
      SAMP8 animals. Unlike cholinergic innervation, the density of adrenergic and
      nitrergic nerves increased in SAMP8 mice. In contrast, smooth muscle sensitivity
      to exogenous noradrenaline (NA) was slightly reduced, whereas cGMP accumulation
      in response to EFS and DEA/NO, and relaxations to DEA/NO and sildenafil, were not
      modified. No changes in the expression of eNOS and in the distribution of
      vimentin-positive ICs were detected in the aged animals. The ACh induced atropine
      sensitive biphasic endothelium-dependent responses involved relaxation at low
      concentrations that turned into contractions at the highest doses. CC relaxation
      was mainly because of the production of NO together with some relaxant
      prostanoid, which did not change in SAMP8 animals. In contrast, the contractile
      component was considerably higher in the aged animals and it was completely
      inhibited by indomethacin. In conclusion, a clear imbalance towards enhanced
      production of contractile prostanoids from the endothelium may contribute to ED
      in the elderly. On the basis of these data, we propose the senescence-accelerated
      mouse model as a reliable tool to analyse the basic ageing mechanisms of the CC. 

PMID- 24737551
TI  - Return to work with back pain: balancing the benefits of work against the efforts
      of being productive.

PMID- 24737552
TI  - Sickness absence, moral hazard, and the business cycle.
AB  - The procyclical nature of sickness absence has been documented by many scholars
      in literature. So far, explanations have been based on labor force composition
      and reduced moral hazard caused by fear of job loss during recessions. In this
      paper, we propose and test a third mechanism caused by reduced moral hazard
      during booms and infections. We suggest that the workload is higher during
      economic booms and thus employees have to go to work despite being sick. In a
      theoretical model focusing on infectious diseases, we show that this will provoke
      infections of coworkers leading to overall higher sickness absence during
      economic upturns. Using state-level aggregated data from 112 German public health
      insurance funds (out of 145 in total), we find that sickness absence due to
      infectious diseases shows the largest procyclical pattern, as predicted by our
      theoretical model.

PMID- 24737553
TI  - A comparative tissue-specific metabolite analysis and determination of
      protodioscin content in Asparagus species used in traditional Chinese medicine
      and Ayurveda by use of laser microdissection, UHPLC-QTOF/MS and LC-MS/MS.
AB  - INTRODUCTION: Asparagus is esteemed in Traditional Chinese Medicine and Ayurveda,
      and it is commercially one of the most important drugs in the global herbal
      market. Comparative metabolite profiling of different species would help in
      determining the similarities and ascertain their validity for being used as
      substitutes for each other. Laser microdissection (LMD) facilitates
      identification of metabolites in specific tissues, and thus it can aid in
      exploration of metabolic pathways in target tissues. OBJECTIVE: To compare tissue
      specific metabolites and protodioscin content of Asparagus cochinchinensis
      (Lour.) Merr. and Asparagus racemosus Willd. used in China and India. METHODS:
      Metabolite analysis of laser-dissected tissues was carried out using UHPLC
      QTOF/MS and LC-MS/MS. The protodioscin contents were determined and the method
      was validated as per the International Conference on Harmonisation of Technical
      Requirements for Registration of Pharmaceuticals for Human Use guidelines.
      RESULTS: Metabolite analysis reveals that the velamen tissue, among other tissues
      such as cortex, vascular bundles and pith, contained maximum components,
      specifically those belonging to the steroidal saponin class. Although the
      metabolite profiles were similar, the content of protodioscin was found to be
      higher in Chinese than Indian species. CONCLUSION: The study provided a suitable
      methodology for metabolite profiling and protodioscin content determination of
      Asparagus by use of LMD, UHPLC-QTOF/MS and LC-MS/MS. The similarities in
      metabolite profiles indicate that Asparagus species from India and China can
      serve as substitute for each other in various therapeutic and pharmaceutical
      applications.

PMID- 24737554
TI  - WITHDRAWN: Treatment for amphetamine dependence and abuse.

PMID- 24737556
TI  - Azacyanines of the pyrrolopyrrole series.
AB  - The reaction of POCl3-activated, readily soluble diketopyrrolopyrrole (DPP) with
      2-aminoheteroaromatics to yield 1:1 and 1:2 hydrogen chelates is described.
      Complexation of these hydrogen chelates with boron reagents results in thermally
      and photochemically stable fluorescent dyes (PP-azacyanines). The 1:2 complexes
      in particular absorb at long wavelengths and are brightly fluorescing. The rich
      photophysics of the new compounds are presented. Both the pronounced vibrational
      fine structure of the S0 -> S1 transitions and the observed fluorescence
      phenomena allow detailed conclusions to be made on the correlation between
      molecular structure and optical properties.

PMID- 24737557
TI  - The FNIH sarcopenia project: rationale, study description, conference
      recommendations, and final estimates.
AB  - BACKGROUND: Low muscle mass and weakness are common and potentially disabling in
      older adults, but in order to become recognized as a clinical condition, criteria
      for diagnosis should be based on clinically relevant thresholds and independently
      validated. The Foundation for the National Institutes of Health Biomarkers
      Consortium Sarcopenia Project used an evidence-based approach to develop these
      criteria. Initial findings were presented at a conference in May 2012, which
      generated recommendations that guided additional analyses to determine final
      recommended criteria. Details of the Project and its findings are presented in
      four accompanying manuscripts. METHODS: The Foundation for the National
      Institutes of Health Sarcopenia Project used data from nine sources of community
      dwelling older persons: Age, Gene/Environment Susceptibility-Reykjavik Study,
      Boston Puerto Rican Health Study, a series of six clinical trials, Framingham
      Heart Study, Health, Aging, and Body Composition, Invecchiare in Chianti,
      Osteoporotic Fractures in Men Study, Rancho Bernardo Study, and Study of
      Osteoporotic Fractures. Feedback from conference attendees was obtained via
      surveys and breakout groups. RESULTS: The pooled sample included 26,625
      participants (57% women, mean age in men 75.2 [+/-6.1 SD] and in women 78.6 [+/
      5.9] years). Conference attendees emphasized the importance of evaluating the
      influence of body mass on cutpoints. Based on the analyses presented in this
      series, the final recommended cutpoints for weakness are grip strength <26kg for
      men and <16kg for women, and for low lean mass, appendicular lean mass adjusted
      for body mass index <0.789 for men and <0.512 for women. CONCLUSIONS: These
      evidence-based cutpoints, based on a large and diverse population, may help
      identify participants for clinical trials and should be evaluated among
      populations with high rates of functional limitations.

PMID- 24737558
TI  - Grip strength cutpoints for the identification of clinically relevant weakness.
AB  - BACKGROUND: Weakness is common and contributes to disability, but no consensus
      exists regarding a strength cutpoint to identify persons at high risk. This
      analysis, conducted as part of the Foundation for the National Institutes of
      Health Sarcopenia Project, sought to identify cutpoints that distinguish weakness
      associated with mobility impairment, defined as gait speed less than 0.8 m/s.
      METHODS: In pooled cross-sectional data (9,897 men and 10,950 women),
      Classification and Regression Tree analysis was used to derive cutpoints for grip
      strength associated with mobility impairment. RESULTS: In men, a grip strength of
      26-32 kg was classified as "intermediate" and less than 26 kg as "weak"; 11% of
      men were intermediate and 5% were weak. Compared with men with normal strength,
      odds ratios for mobility impairment were 3.63 (95% CI: 3.01-4.38) and 7.62 (95%
      CI 6.13-9.49), respectively. In women, a grip strength of 16-20 kg was classified
      as "intermediate" and less than 16 kg as "weak"; 25% of women were intermediate
      and 18% were weak. Compared with women with normal strength, odds ratios for
      mobility impairment were 2.44 (95% CI 2.20-2.71) and 4.42 (95% CI 3.94-4.97),
      respectively. Weakness based on these cutpoints was associated with mobility
      impairment across subgroups based on age, body mass index, height, and disease
      status. Notably, in women, grip strength divided by body mass index provided
      better fit relative to grip strength alone, but fit was not sufficiently improved
      to merit different measures by gender and use of a more complex measure.
      CONCLUSIONS: Cutpoints for weakness derived from this large, diverse sample of
      older adults may be useful to identify populations who may benefit from
      interventions to improve muscle strength and function.

PMID- 24737559
TI  - Cutpoints for low appendicular lean mass that identify older adults with
      clinically significant weakness.
AB  - BACKGROUND: Low lean mass is potentially clinically important in older persons,
      but criteria have not been empirically validated. As part of the FNIH (Foundation
      for the National Institutes of Health) Sarcopenia Project, this analysis sought
      to identify cutpoints in lean mass by dual-energy x-ray absorptiometry that
      discriminate the presence or absence of weakness (defined in a previous report in
      the series as grip strength <26kg in men and <16kg in women). METHODS: In pooled
      cross-sectional data stratified by sex (7,582 men and 3,688 women),
      classification and regression tree (CART) analysis was used to derive cutpoints
      for appendicular lean body mass (ALM) that best discriminated the presence or
      absence of weakness. Mixed-effects logistic regression was used to quantify the
      strength of the association between lean mass category and weakness. RESULTS: In
      primary analyses, CART models identified cutpoints for low lean mass (ALM
      <19.75kg in men and <15.02kg in women). Sensitivity analyses using ALM divided by
      body mass index (BMI: ALMBMI) identified a secondary definition (ALMBMI <0.789 in
      men and ALMBMI <0.512 in women). As expected, after accounting for study and age,
      low lean mass (compared with higher lean mass) was associated with weakness by
      both the primary (men, odds ratio [OR]: 6.9 [95% CI: 5.4, 8.9]; women, OR: 3.6
      [95% CI: 2.9, 4.3]) and secondary definitions (men, OR: 4.3 [95% CI: 3.4, 5.5];
      women, OR: 2.2 [95% CI: 1.8, 2.8]). CONCLUSIONS: ALM cutpoints derived from a
      large, diverse sample of older adults identified lean mass thresholds below which
      older adults had a higher likelihood of weakness.

PMID- 24737560
TI  - Criteria for clinically relevant weakness and low lean mass and their
      longitudinal association with incident mobility impairment and mortality: the
      foundation for the National Institutes of Health (FNIH) sarcopenia project.
AB  - BACKGROUND: This analysis sought to determine the associations of the Foundation
      for the National Institutes of Health Sarcopenia Project criteria for weakness
      and low lean mass with likelihood for mobility impairment (gait speed <= 0.8 m/s)
      and mortality. Providing validity for these criteria is essential for research
      and clinical evaluation. METHODS: Among 4,411 men and 1,869 women pooled from 6
      cohort studies, 3-year likelihood for incident mobility impairment and mortality
      over 10 years were determined for individuals with weakness, low lean mass, and
      for those having both. Weakness was defined as low grip strength (<26kg men and
      <16kg women) and low grip strength-to-body mass index (BMI; kg/m(2)) ratio (<1.00
      men and <0.56 women). Low lean mass (dual-energy x-ray absorptiometry) was
      categorized as low appendicular lean mass (ALM; <19.75kg men and <15.02kg women)
      and low ALM-to-BMI ratio (<0.789 men and <0.512 women). RESULTS: Low grip
      strength (men: odds ratio [OR] = 2.31, 95% confidence interval [CI] = 1.34-3.99;
      women: OR = 1.99, 95% CI 1.23-3.21), low grip strength-to-BMI ratio (men: OR =
      3.28, 95% CI 1.92-5.59; women: OR = 2.54, 95% CI 1.10-5.83) and low ALM-to-BMI
      ratio (men: OR = 1.58, 95% CI 1.12-2.25; women: OR = 1.81, 95% CI 1.14-2.87), but
      not low ALM, were associated with increased likelihood for incident mobility
      impairment. Weakness increased likelihood of mobility impairment regardless of
      low lean mass. Mortality risk patterns were inconsistent. CONCLUSIONS: These
      findings support our cut-points for low grip strength and low ALM-to-BMI ratio as
      candidate criteria for clinically relevant weakness and low lean mass. Further
      validation in other populations and for alternate relevant outcomes is needed.

PMID- 24737561
TI  - An evidence-based comparison of operational criteria for the presence of
      sarcopenia.
AB  - BACKGROUND: Several consensus groups have previously published operational
      criteria for sarcopenia, incorporating lean mass with strength and/or physical
      performance. The purpose of this manuscript is to describe the prevalence,
      agreement, and discrepancies between the Foundation for the National Institutes
      of Health (FNIH) criteria with other operational definitions for sarcopenia.
      METHODS: The FNIH Sarcopenia Project used data from nine studies including: Age,
      Gene and Environment Susceptibility-Reykjavik Study; Boston Puerto Rican Health
      Study; a series of six clinical trials from the University of Connecticut;
      Framingham Heart Study; Health, Aging, and Body Composition Study; Invecchiare in
      Chianti; Osteoporotic Fractures in Men Study; Rancho Bernardo Study; and Study of
      Osteoporotic Fractures. Participants included in these analyses were aged 65 and
      older and had measures of body mass index, appendicular lean mass, grip strength,
      and gait speed. RESULTS: The prevalence of sarcopenia and agreement proportions
      was higher in women than men. The lowest prevalence was observed with the FNIH
      criteria (1.3% men and 2.3% women) compared with the International Working Group
      and the European Working Group for Sarcopenia in Older Persons (5.1% and 5.3% in
      men and 11.8% and 13.3% in women, respectively). The positive percent agreements
      between the FNIH criteria and other criteria were low, ranging from 7% to 32% in
      men and 5% to 19% in women. However, the negative percent agreement were high
      (all >95%). CONCLUSIONS: The FNIH criteria result in a more conservative
      operational definition of sarcopenia, and the prevalence was lower compared with
      other proposed criteria. Agreement for diagnosing sarcopenia was low, but
      agreement for ruling out sarcopenia was very high. Consensus on the operational
      criteria for the diagnosis of sarcopenia is much needed to characterize
      populations for study and to identify adults for treatment.

PMID- 24737562
TI  - Skeletal muscle function deficit: a new terminology to embrace the evolving
      concepts of sarcopenia and age-related muscle dysfunction.
AB  - BACKGROUND: Concerns remain as to the best terminology to embrace sarcopenia's
      evolving conceptualization. Many of these concerns stem from the fact that age
      related decrements in muscle performance associated with physical impairment are
      only partially explained by decreases in muscle mass and that other
      pathophysiologic factors contribute to age-related impairments in muscle
      performance. METHODS: Review of literature on the evolving conceptualization of
      sarcopenia since its early definition in 1989 and concerns with terminology.
      RESULTS: Early definitions of sarcopenia were based solely on muscle mass in
      relationship to the range of muscle within a reference population. Subsequent
      definitions added performance criteria to muscle mass alone. The Foundation for
      the National Institutes of Health Sarcopenia Project identified criteria for
      clinically relevant low muscle strength (weakness) and low lean mass. Progress on
      the sarcopenia's evolving definitions has not been accompanied by recommendations
      on specific terminologies that address the lack of sufficient specificity from
      the use of an anatomic term to define a functional condition with numerous now
      known nonanatomic contributory factors. Skeletal Muscle Function Deficit is a
      broader construct that accommodates a set of diagnoses that includes both
      sarcopenia and other age-related muscle dysfunctions. CONCLUSIONS: Skeletal
      Muscle Function Deficit is proposed as a new terminology to embrace the evolving
      conceptualization of sarcopenia and other age-related muscle dysfunctions. It
      comprises a variety of contributory etiologies and has the potential to provide a
      framework for developing diagnostic categories that are useful for both clinical
      practice and research.

PMID- 24737569
TI  - Pre-control characterization of hippocampal epileptic models.
AB  - This paper presents a dynamical characterization of epileptic seizures in animal
      models. Inter-hippocampal recordings of two animal models of seizures, kindling
      and pilocarpine, were analyzed by nonlinear analytic tools. The aim is to assess
      and differentiate pathophysiological states and behavioral phases of a status
      epilepticus. The achieved results indicates that stage V of Racine classification
      could be identified as the transition of dynamical indicators exhibit a monotonic
      decline up to this stage and an increase after that. Furthermore, concentration
      of data points on a small region of state space, achieved by our analysis,
      promises that a local nonlinear control may cause neuromodulation. This
      feasibility gets more strengthen by achievements of this paper on successful
      tracking of drifts of unstable periodic orbits at seizure onset. Nonlinear
      control algorithms could afterwards be designed to find suitable instances for
      inserting perturbations and steer the dynamics of system toward a desired
      dynamical operating mode.

PMID- 24737570
TI  - Ectopic expression of micro-RNA-1, 21 and 125a in peripheral blood immune cells
      is associated with chronic HBV infection.
AB  - Micro-RNAs (miRNAs) play key roles in regulating genes of the immune system. The
      aim of this study was to examine the expression of miR-1, 21 and 125a in the
      immune cells taken from the peripheral blood of patients suffering from chronic
      HBV infection (CHB). This cross-sectional study was performed on 60 CHB patients
      and 60 healthy controls and expression of miR-1, 21 and 125a was evaluated using
      quantitative Real-Time PCR. The results showed that expression of miR-1, 21 and
      125a was significantly increased in CHB patients in comparison to healthy
      controls. Based on our results it may be concluded that increased expression of
      miR-1, 21 and 125a is significantly associated with CHB and may play key roles in
      the induction of impaired immune responses in CHB patients. 

PMID- 24737571
TI  - Isolation and characterization of a pathogenesis-related protein 10 gene (GmPR10)
      with induced expression in soybean (Glycine max) during infection with
      Phytophthora sojae.
AB  - In previous study, a cDNA library enriched for mRNAs encoding ESTs that increased
      in abundance during infection with Phytophthora sojae was constructed by
      suppression subtractive hybridization from leaf tissues of a high resistant
      soybean, and an EST homologous to the class 10 of pathogenesis-related (PR)
      proteins was identified to be up-regulated by microarray and real-time PCR. Here,
      the full-length cDNA (termed GmPR10, GenBank accession number FJ960440;
      ADC31789.1) of the EST was isolated by rapid amplification of cDNA ends, and
      contains an open reading frame of 474 bp. The GmPR10 protein included a "P-loop''
      motif. The constitutive transcript abundance of GmPR10 in soybean was the highest
      in leaves, followed by roots and stems. Further analysis showed that GmPR10 mRNA
      abundance was increased during infection with P. sojae following leaf treatments
      with gibberellin (GA3), hydrogen peroxide (H2O2), salicylic acid (SA), and
      abscisic acid (ABA). The dialytically renatured GmPR10 protein significantly
      inhibited P. sojae hyphal growth and exhibited RNase activity. Transgenic tobacco
      and soybean plants overexpressing GmPR10 showed increased resistance to P.
      nicotianae Breda and P. sojae, respectively. These results suggest that the
      GmPR10 protein plays an important role in host defense against P. sojae
      infection. To the best of our knowledge, this is the first report on the
      functional characterization of a PR10 protein from soybean in defense against P.
      sojae. 

PMID- 24737573
TI  - Using visual evoked potentials for the early detection of amnestic mild cognitive
      impairment: a pilot investigation.
AB  - OBJECTIVE: Amnesic mild cognitive impairment (MCIa) is often characterized as an
      early stage of Alzheimer's dementia (AD). The latency of the P2, an
      electroencephalographic component of the flash visual evoked potential (FVEP), is
      significantly longer in those with AD or MCIa when compared with controls. The
      present investigation examined the diagnostic accuracy of several FVEP-P2
      procedures in distinguishing people with MCIa and controls. METHODS: The latency
      of the FVEP-P2 was measured in participants exposed to a single flash condition
      and five double flash conditions. The double flash conditions had different inter
      stimulus intervals between the pair of strobe flashes. RESULTS: Significant group
      differences were observed in the single flash and two of the double flash
      conditions. One of the double flash conditions (100 ms) displayed a higher
      predictive accuracy than the single flash condition, suggesting that this novel
      procedure may have more diagnostic potential. Participants with MCIa displayed
      similar P2 latencies across conditions, while controls exhibited a consistent
      pattern of P2 latency differences. These differences demonstrate that the double
      stimulation procedure resulted in a measurable refractory effect for controls but
      not for those with MCIa. CONCLUSIONS: The pattern of P2 group differences
      suggests that those with MCIa have compromised cholinergic functioning that
      results in impaired visual processing. Results from the present investigation
      lend support to the theory that holds MCIa as an intermediate stage between
      normal healthy aging and the neuropathology present in AD. Measuring the FVEP-P2
      during several double stimulation conditions could provide diagnostically useful
      information about the health of the cholinergic system.

PMID- 24737572
TI  - TGF-beta signaling-dependent alleviation of dextran sulfate sodium-induced
      colitis by mesenchymal stem cell transplantation.
AB  - Alleviation of dextran sulfate sodium (DSS)-induced colitis was shown after by
      transplantation of bone marrow derived cells in mice. Nevertheless, the
      underlying mechanism remains elusive. In the present study, we transplanted
      primary mouse mesenchymal stem cells (MSC) into isogeneic mice with DSS-induced
      colitis. We found that MSC transplantation significantly alleviated the DSS
      induced colitis. Inhibition of transforming growth factor beta (TGF-beta)
      signaling abrogated the therapeutic effect of MSC transplantation on DSS-colitis,
      suggesting a TGF-beta signaling-dependent manner. Moreover, MSC transplantation
      seemed to induce M2 macrophage polarization, which appeared to be the major
      source of TGF-beta in this model. Our data thus demonstrate that MSC
      transplantation may activate TGF-beta signaling pathways to promote the recovery
      of DSS-colitis. 

PMID- 24737574
TI  - Design, synthesis, and activity evaluation of GK/PPARgamma dual-target-directed
      ligands as hypoglycemic agents.
AB  - Based on the multi-target strategy to treat type 2 diabetes mellitus (T2DM),
      glucokinase/peroxisome proliferator-activated receptor gamma (GK/PPARgamma) dual
      target molecules were constructed by the rational combination of pharmacophores
      from known GK activators and PPARgamma agonists. A series of dual-target agents
      were designed and synthesized, and their capacities to induce GK and PPARgamma
      transcriptional activity were evaluated. Three of these compounds showed
      particularly high potency toward GK, moderate activity toward PPARgamma, and
      their structure-activity relationships were preliminarily analyzed. The putative
      binding modes of one of the most promising compounds were also explored by
      molecular docking simulations with GK and PPARgamma.

PMID- 24737575
TI  - Spinal ephrinB/EphB signalling contributed to remifentanil-induced hyperalgesia
      via NMDA receptor.
AB  - BACKGROUND: One of the major unresolved issues in treating pain is the
      paradoxical hyperalgesia produced by opiates, and accumulating evidence implicate
      that EphBs receptors and ephrinBs ligands are involved in mediation of spinal
      nociceptive information and central sensitization, but the manner in which
      ephrinB/EphB signalling acts on spinal nociceptive information networks to
      produce hyperalgesia remains enigmatic. The objective of this research was to
      investigate the role of ephrinB/EphB signalling in remifentanil-induced
      hyperalgesia (RIH) and its downstream effector. METHODS: We characterized the
      remifentanil-induced pain behaviours by evaluating thermal hyperalgesia and
      mechanical allodynia in a rat hind paw incisional model. Protein expression of
      EphB1 receptor and ephrinB1 ligand in spinal dorsal horn cord was determined by
      Western blotting, and Fos was determined by immunohistochemistry assay,
      respectively. To figure out the manner in which ephrinB/EphB signalling acts with
      N-methyl-d-aspartic acid (NMDA) receptor, we used MK-801, an antagonist of NMDA
      receptor, trying to suppressed the hyperalgesia induced by ephrinB1-Fc, an
      agonist of ephrinB/EphB. RESULTS: Continuing infusion of remifentanil produced a
      thermal hyperalgesia and mechanical allodynia, which was accompanied with
      increased protein expression of spinal-level EphB1 receptor, ephrinB1 ligand and
      Fos; what appeared above was suppressed by pretreatment with EphB1-Fc, an
      antagonist of ephrinB/EphB or MK-801, and increased pain behaviours induced by
      intrathecal injection of ephrinB1-Fc, an agonist of ephrinB/EphB, were suppressed
      by MK-801. CONCLUSIONS: Our findings indicated that ephrinB/EphB signalling is
      involved in RIH. EphrinB/EphB signalling might be the upstream of NMDA receptor.

PMID- 24737576
TI  - Acute renal failure associated with the new BRAF inhibitor vemurafenib: a case
      series of 8 patients.
AB  - BACKGROUND: Vemurafenib is a BRAF inhibitor that has become the cornerstone of
      metastatic or inoperable melanoma therapy since its approval in 2011 in the
      United States and 2012 in Europe. This targeted therapy has shown impressive
      results in terms of increased progression-free and overall survival as compared
      to dacarbazine. The safety profile did not include any renal manifestations at
      that time. METHODS: This report is the first case series of 8 patients who
      experienced significant to severe renal insufficiency under vemurafenib
      treatment. RESULTS: This case series shows that vemurafenib may induce
      potentially severe acute renal failure, including renal sequelae and persistent
      kidney disease in some cases. CONCLUSIONS: Further studies are needed to
      investigate the effects of vemurafenib on the kidneys. Meanwhile, renal function
      should be closely monitored in treated patients for early detection of any renal
      dysfunction occurrence. Cancer 2014;120:2158-2163. (c) 2014 American Cancer
      Society.

PMID- 24737577
TI  - WITHDRAWN: Case management for persons with substance use disorders.

PMID- 24737578
TI  - Facile synthesis and theoretical conformation analysis of a triazine-based double
      decker rotor molecule with three anthracene blades.
AB  - The facile synthesis of a rotor-shaped compound with two stacked triazine units,
      which are symmetrically connected by three anthracene blades through oxygen
      linkers, is presented. This new double-decker, which is a potential monomer for
      two-dimensional polymerization, was synthesized by using readily available, cheap
      building blocks, exploiting the known selectivity difference for the nucleophilic
      substitution of cyanuric chloride. The crystal structure of a C3h symmetric rotor
      shaped compound with 9,10-dihydroanthracene blades, which is a direct precursor
      to the targeted monomer, and the crystal structure of the new double-decker with
      the desired C3h symmetry, are also reported. The synthetic efforts were preceded
      by a computational analysis, which was triggered by the question of
      conformational stability of the potential monomer. Two stable conformers could be
      found, and the barrier for the transition path in the gas phase between these
      conformers was determined by quantum chemical calculations. Exploratory Born
      Oppenheimer molecular-dynamics simulations revealed a strong influence of solvent
      solute interactions on the stability of the conformers, which resulted in an
      energetic preference of the C3h symmetric conformation of the double-decker. 

PMID- 24737579
TI  - AR and SRD5A2 gene mutations in a series of 51 Turkish 46,XY DSD children with a
      clinical diagnosis of androgen insensitivity.
AB  - 46,XY disorders of sex development (DSD) are caused by disorders of gonadal
      development, androgen biosynthesis and receptor (AR) defects. Although,
      clinical/biochemical features help in distinguishing specific aetiologies, there
      are overlaps which necessitate molecular analyses for the definitive diagnosis.
      To test precision of our clinical diagnosis of androgen insensitivity (AIS) by
      analysing AR and then SRD5A2 genes, patients were recruited at Marmara University
      Hospital and molecular analyses were performed at Vall d'Hebron Research
      Institute. Among 101 46,XY DSD patients, 46 index and five siblings (nine
      complete, 42 partial) with clinical/biochemical data suggestive of AIS and
      stimulated T/DHT ratio <25 were selected. AR and then SRD5A2 genes were
      sequenced. We detected AR mutations in 11 patients [seven index and four siblings
      (22% of all and 15% of index patients)] and SRD5A2 mutations in six [five index
      and one sibling (12% of all and 11% of index)]. AR mutation detection rate was
      6/9 in all CAIS and 4/7 in the index (67 and 57% respectively) and 5/42 in all
      PAIS and 3/40 in the index (12 and 7.5% respectively). The eight mutations
      detected in the AR gene were as follows: p.Q58L, p.P392S, p.R609K, p.R775H,
      p.R856H, p.A871A, p.V890M and p.F892L, with p.A871A and p.F892L being novel.
      Further six patients had SRD5A2 mutations which were as follows: p.L73WfsX59,
      p.Y91H, p.R171S and p.G196S, the first being novel. Hormonal data in those with
      AR mutations, SRD5A2 mutations and no mutations were not statistically different.
      In conclusion, a significant proportion of children with presumptive diagnosis of
      AIS has a normal AR gene. The less severe the phenotype, the less likely is the
      chance of demonstrating a mutation. Furthermore, a significant number of children
      with presumptive diagnosis of AIS have mutations in SRD5A2 gene and are
      clinically and biochemically indistinguishable from AIS. 

PMID- 24737580
TI  - Selective impairment of attention networks in breast cancer patients receiving
      chemotherapy treatment.
AB  - INTRODUCTION: Complaints about attention disorders are common among breast cancer
      survivors who have undergone chemotherapy treatment. However, it is not known
      whether these complaints indicate a global attention deficit or the selective
      impairment of attention networks. OBJECTIVE: This study sought to investigate the
      attentional abilities of breast cancer patients after chemotherapy treatment
      using the attention network test (ANT). METHODS: The participants included breast
      cancer patients who had undergone chemotherapy (CT, N = 58), patients who had not
      undergone chemotherapy (non-CT, N = 53), and matched healthy controls (HC, N =
      55). All participants completed the ANT, which provides measures of three
      independent attention networks (alerting, orienting, and executive control) and
      neuropsychological background tests. RESULTS: Our results indicated that the
      chemotherapy-treated breast cancer patients had significant deficits in the
      alerting and executive control networks but not in the orienting network. The CT
      group scored significantly lower in several cognitive tasks, including attention,
      memory, and information processing tasks, relative to the other two groups.
      Additionally, significant correlations were found between information processing
      and the efficiency of the executive control network within the CT group.
      CONCLUSIONS: These results suggest that the three attention networks were
      selectively impaired following chemotherapy treatment, which affected different
      brain areas in the breast cancer survivors.

PMID- 24737581
TI  - Clinical significance of Ki-67 and p53 expression in curatively resected non
      small cell lung cancer.
AB  - The aim of this study is to explore the association of Ki-67 and p53 expression
      with prognosis in non-small cell lung cancer (NSCLC) patients who underwent
      curative resection. We retrospectively identified 116 consecutive patients with
      stages I-III NSCLC who underwent curative resection at a single center from
      January 2007 to December 2012. Ki-67 and p53 expression was assessed by
      immunohistochemistry. Data on clinicopathologic features and survival were
      collected retrospectively. Ki-67 expression in 109 samples and p53 expression in
      115 patients were analyzed. According to the results, 108 patients (99 %) showed
      at least some expression of Ki-67. The median Ki-67 expression level was 30 %.
      Positive p53 expression was observed in 91 (79 %) patients. Higher Ki-67
      expression (>40 %) was significantly more frequent in male (26 vs. 4 % in female,
      p=0.002), ever-smoker (31 vs. 10 % in never-smoker, p=0.024), and non
      adenocarcinoma (30 vs. 11 % of adenocarcinoma, p=0.012) patients. In univariable
      analysis, median disease-free survival (DFS) was shorter with higher Ki-67
      expression (16.1 vs. 61.9 months in those with lower Ki-67 expression, p=0.005),
      and p53 expression did not show an association with DFS. Among 42 patients with
      stage I NSCLC who did not receive adjuvant chemotherapy, DFS was significantly
      worse in patients with higher Ki-67 expression (2-year DFS rate 57 vs. 88 %,
      p=0.018). In a Cox regression model, higher Ki-67 expression (>40 %) was a
      significant independent prognostic factor associated with poorer DFS (HR 2.9, 95
      % CI 1.3-6.2) along with TNM stage and age. Higher Ki-67 expression (>40 %)
      showed an independent association with shorter DFS in NSCLC patients who
      underwent curative resection.

PMID- 24737582
TI  - PLCE1 rs2274223 polymorphism contributes to risk of esophageal cancer: evidence
      based on a meta-analysis.
AB  - We sought to reassess the association of PLCE1 rs2274223 and susceptibility to
      esophageal cancer (EC) through a meta-analysis of published case-control studies.
      Using the PubMed and Embase, we identified nine articles including fourteen case
      control studies (15,225 cases and 23,620 controls). ORs and 95 % confidence
      intervals (CIs) of GG vs. AA, GG + GA vs. AA, GG vs. GA + AA, G vs. A, and AG vs.
      AA genetic models were estimated for each study. All of the genetic models
      indicated a statistically significant positive association with EC risk. The
      association appeared most pronounced for carriers of GG genotype (GG vs. AA: OR,
      1.35; 95 % CI, 1.17 to 1.57), and weakest for individuals carrying GA genotype
      (GA vs. AA: OR, 1.13; 95 % CI, 1.05 to 1.23). Stratification analyses showed
      similar results in the population of Asians and in esophageal squamous cell
      carcinoma (ESCC). This meta-analysis provides strong statistical evidence for an
      elevated risk of EC associated with PLCE1 rs2274223. The association remains
      significant in Asian population and ESCC. Further investigations are warranted to
      validate these findings.

PMID- 24737583
TI  - The significant diagnostic value of human telomerase RNA component (hTERC) gene
      detection in high-grade cervical lesions and invasive cancer.
AB  - Gains of 3q26 chromosome region, where the human telomerase RNA gene (hTERC) is
      located, have been previously documented in cervical carcinomas. However,
      published data on this subject are inconclusive. Therefore, we performed a meta
      analysis to evaluate the diagnostic value of hTERC in high-grade cervical lesions
      and invasive cancer. We searched all the eligible studies through PubMed, EMBASE,
      and the Cochrane Library database without language limitation. Studies were
      assessed for quality using quality assessment of diagnostic accuracy studies
      (QUADAS). Positive likelihood ratio (PLR) and negative likelihood ratio (NLR)
      were pooled separately and compared with overall accuracy measures of diagnostic
      odds ratio (DOR) and symmetric summary receiver operating characteristic (SROC).
      The PLR and NLR and their 95 % confidence interval (CI) were calculated using a
      fixed effects model according to the Mantel-Haensed method and random effects
      model based on the work of Der Simonian and laird, respectively. A total of 12
      studies were included for the analysis. The pooled sensitivity was 0.81 (95 % CI,
      0.80-0.82). The pooled specificity was 0.83 (95 % CI, 0.82-0.84). The DOR
      estimate was performed, and the result was 17.37. Our meta-analysis showed that
      the detection of genomic amplification of hTERC is a noninvasive and effective
      approach for high-grade cervical lesions and invasive cancer.

PMID- 24737585
TI  - Cyclin D1 (CCND1) G870A polymorphisms and cervical cancer susceptibility: a meta
      analysis based on ten case-control studies.
AB  - Many studies have evaluated the association between cyclin D1 (CCND1) G870A
      polymorphism and cervical cancer susceptibility. However, these studies showed
      inconsistent results. The aim of this study was to derive a more precise
      estimation of this association. We searched PubMed and Embase for related studies
      that had been published in English, and ten case-control studies with a total of
      2,864 cases and 3,898 controls were finally identified to be eligible studies in
      the meta-analysis. The association was assessed by summarizing the odds ratios
      (ORs) with the corresponding 95 % confidence intervals (CIs). Overall, there was
      no significant association between cyclin D1 (CCND1) G870A polymorphism and
      cervical cancer risk (for the allele model A vs. G: OR = 1.02, 95 % CI 0.88-1.19,
      p = 0.76; for the co-dominant model AA vs. GG: OR = 1.03, 95 % CI 0.75-1.41, p =
      0.85; for the dominant model AA + GA vs. GG: OR = 1.00, 95 % CI 0.78-1.28, p =
      0.99; for the recessive comparison AA vs. GA + GG: OR = 1.06, 95 % CI 0.85-1.32,
      p = 0.62). In subgroup analysis by ethnicity, no significant difference was found
      in both Asians and Caucasians. In summary, the present meta-analysis provides
      evidence that genotypes for the cyclin D1 (CCND1) G870A polymorphism may be not
      associated with genetic susceptibility of cervical cancer.

PMID- 24737584
TI  - Urothelial carcinoma associated 1 is a hypoxia-inducible factor-1alpha-targeted
      long noncoding RNA that enhances hypoxic bladder cancer cell proliferation,
      migration, and invasion.
AB  - Urothelial carcinoma associated 1 (UCA1) has been identified as an oncogenic long
      noncoding RNA (lncRNA) that is involved in bladder cancer progression and acts as
      a diagnostic biomarker for bladder carcinoma. Here, we studied the expression and
      function of lncRNA-UCA1 in the hypoxic microenvironment of bladder cancer. The
      expression and transcriptional activity of lncRNA-UCA1 were measured by
      quantitative real-time polymerase chain reaction and luciferase assays. Cell
      proliferation and apoptosis were evaluated by MTT assays and flow cytometry. Cell
      migration and invasion were detected by wound healing, migration, and invasion
      assays. The binding of hypoxia-inducible factor-1alpha (HIF-1alpha) to hypoxia
      response elements (HREs) in the lncRNA-UCA1 promoter was confirmed by
      electrophoretic mobility shift assay and chromatin immunoprecipitation. HRE
      mutations were generated by using a site-directed mutagenesis kit, and HIF-1alpha
      knockdown was mediated by small interfering RNA. The effect of HIF-1alpha
      inhibition by YC-1 on lncRNA-UCA1 expression was also examined. LncRNA-UCA1 was
      upregulated by hypoxia in bladder cancer cells. Under hypoxic conditions, lncRNA
      UCA1 upregulation increased cell proliferation, migration, and invasion and
      inhibited apoptosis. The underlying mechanism of hypoxia-upregulated lncRNA-UCA1
      expression was that HIF-1alpha specifically bound to HREs in the lncRNA-UCA1
      promoter. Furthermore, HIF-1alpha knockdown or inhibition could prevent lncRNA
      UCA1 upregulation under hypoxia. These findings revealed the mechanism of lncRNA
      UCA1 upregulation in hypoxic bladder cancer cells and suggested that effective
      blocking of lncRNA-UCA1 expression in the hypoxic microenvironment of bladder
      cancer could be a novel therapeutic strategy.

PMID- 24737586
TI  - DNA damage-inducible gene, UNC5A, functions as a tumor-suppressor in bladder
      cancer.
AB  - UNC5 receptors are putative tumor suppressors whose expressions are lost in some
      cancers, but the role of UNC5A during DNA damage in bladder cancer remains
      undefined. To investigate into the potential function of UNC5A in bladder cancer,
      we examined UNC5A expression with real-time RT-PCR and Western blotting in
      bladder cancer specimens and analyzed the effects of chemotherapeutic drug on the
      expression level of UNC5A and knocking down of UNC5A on chemotherapeutic drug
      mediated cell death. In this current study, we found low expression of UNC5A in
      bladder cancer, an effective induction of UNC5A by cisplatin in bladder cancer
      cell lines with wt p53, and a significant reduction of cisplatin-mediated cell
      death following silencing the endogenous UNC5A. Moreover, colony formation assay
      indicated that reexpression of UNC5A inhibited the survival of 5637 cells.
      Together, these data suggest an important role for UNC5A, a candidate tumor
      suppressor, in predicting response to DNA damage induced by chemotherapeutic drug
      and regulating cell death in bladder cancer. 

PMID- 24737587
TI  - Serum Zta antibody of Epstein-Barr virus exerts potential function in the
      diagnosis of nasopharyngeal cancer.
AB  - The diagnosis of nasopharyngeal cancer (NPC) remains a clinical challenge. Many
      studies have assessed the diagnostic potential of Zta antibody of the Epstein
      Barr virus (EBV) in NPC patients but with controversial results. This study aims
      to summarize the overall diagnostic performance of EBV Zta antibody in NPC. Based
      on a comprehensive search of the Pubmed and Embase, Web of Science, Chinese
      National Knowledge Infrastructure (CNKI), Wanfang Databases and China Citation
      Databases, we identified outcome data from all articles estimating diagnostic
      accuracy of EBV Zta antibody for NPC. A summary estimation for sensitivity,
      specificity, and other diagnostic indexes were pooled using a bivariate model.
      The overall measure of accuracy was calculated using summary receiver operating
      characteristic curve and the area under curve (AUC) was calculated. According to
      our inclusion criteria, 17 studies with 11,822 subjects (1,645 NPC cases, 10,177
      controls) were included. The summary estimates were: sensitivity 0.87 (95 %
      confidence interval [CI] = 0.86-0.89), specificity 0.94 (95 % CI = 0.93-0.94),
      positive likelihood ratio 8.05 (95 % CI = 5.59-11.59), negative likelihood ratio
      0.16 (95 % CI = 0.12-0.21), diagnostic odds ratio 52.93 (95 % CI = 29.95-93.56),
      the AUC and Q* index were 0.9352 and 0.8714, respectively. In conclusion, serum
      EBV Zta had a better diagnostic performance for NPC. Further studies should be
      performed to confirm our findings.

PMID- 24737588
TI  - Expression and biological role of cytoglobin in human ovarian cancer.
AB  - Loss of cytoglobin is found to be involved in the progression of several human
      cancers. However, its expression pattern and biological roles in human ovarian
      cancers are not clear. In this study, we examined cytoglobin expression in 118
      archived ovarian cancer specimens using immunohistochemistry. A total of 72
      specimens (61.0 %) showed cytoglobin downregulation. cytoglobin downregulation
      positively correlated with advanced FIGO stage and tumor grade. Cytoglobin
      plasmid transfection was performed in SKOV3 cell line and siRNA knockdown was
      carried out in SW626 cell line. MTT, colony formation assay and matrigel invasion
      assay were carried out to assess the role of cytoglobin on cell proliferation and
      invasion. Cytoglobin overexpression inhibited cell growth, invasion, cell cycle
      progression and cyclin D1 expression in SKOV3 cell line and its depletion
      promoted cell proliferation, invasion, cell cycle transition and cyclin D1
      expression. In conclusion, cytoglobin is downregulated in ovarian cancers and
      associated with advanced stage. Our data provides evidence that cytoglobin
      regulates the ovarian cancer cell proliferation and invasion.

PMID- 24737589
TI  - Investigation of a novel biomarker, neuropilin-1, and its application for poor
      prognosis in acute myeloid leukemia patients.
AB  - According to the previous studies, numerous biomarkers impact on the prognosis of
      acute myeloid leukemia (AML) and the prediction for AML had been improved
      tremendously in the past decades. However, accurate risk-stratification at
      diagnosis or prognosis remained difficult. In order to further investigate the
      prognosis evaluation biomarker, the transcription or expression of neuropilin-1
      (NRP-1) in 87 AML patients and 32 non-malignant controls were examined. Real-time
      quantitative polymerase chain reaction (RT-PCR) and Western blot were used to
      detect the NRP-1 expression. Clinical data were collected and analyzed for the 87
      AML patients. The results indicated that high NRP-1 expression discriminated the
      complete remission (CR) rate of AML patients (22.12 % vs. 68.04 % for AML, P <
      0.01). De novo AML patients tended to express higher NRP-1 proteins than relapsed
      AML patients. The overall survival (OS) and relapse-free survival (RFS) rate of
      the high NRP-1 expression patients decreased significantly compared with the low
      NRP-1 expression patients (P < 0.001). NRP-1 was revealed to be an independent
      risk factor for OS in AML (P = 0.003). In conclusion, NRP-1 could predict the
      shorter OS and RFS rate, and also related with the CR response in AML. Therefore,
      NRP-1 may act as a more aggressive and promising predictor for the poor prognosis
      of AML.

PMID- 24737590
TI  - Hydrophilic interaction electrokinetic chromatography using bio-based
      nanofillers.
AB  - Hydrophilic interaction (HI)-based separation like HILIC is effective for
      analyzing hydrophilic biological samples such as carbohydrates, peptides, and
      metabolites. To overcome the drawbacks of conventional HILIC such as large
      consumption of organic solvents and easy deterioration of the separation column,
      we developed HI electrokinetic chromatography (EKC) by employing bio-based
      nanomaterials as the hydrophilic pseudostationary phase. By mechanical/chemical
      treatments, cellulose, chitin, and chitosan were processed to 10-nm wide
      nanofibers/nanowhiskers (NFs/NWs), which are longer/shorter than 1000/200 nm,
      respectively. In HI-EKC of oligosaccharides using 0.001% uncharged cellulose NFs,
      strong interaction was observed for the large-size oligosaccharides with the
      retention factors (k) of up to 1.56, indicating a HILIC-mode interaction. In HI
      EKC with 0.1% positively charged chitosan NFs, benzenedisulfonic acid,
      benzenesulfonic acid (BS), and p-hydroxy BS (HBS) had k values of 0.036, 0.018,
      and 0.018, respectively, suggesting that the ion-exchange interaction mainly
      occurred via sulfonate groups. Finally, HI-EKC was demonstrated using 0.05%
      chitin or chitosan NWs. In both cases using chitin and chitosan NWs, HBS showed
      much stronger interaction with k > 0.192 compared with BS with k < 0.070. It
      indicated structural difference between NFs and NWs affected the HI behavior in
      terms of both the ion-exchange and HILIC modes. 

PMID- 24737592
TI  - The coordination chemistry of pentafluorophenylphosphino pincer ligands to
      platinum and palladium.
AB  - The synthesis of electron-poor PCP pincer ligands 1,3-((C6F5)2PO)2C6H4, 1,3
      ((C6F5)2PCH2)2C6H4, and 1-((C6F5)2PO)-3-(tBu2PCH2)C6H4, and their coordination
      chemistry to platinum and palladium is described. The most electron-poor ligand
      1,3-((C6F5)2PO)2C6H4 (POCOPH) reacts with Group 10 metal chloride precursors to
      form a range of unusual cis, trans-dimers of the type kappa(2)-P,P
      [(POCOPH)MCl(L)]2 (M = Pt, Pd; L = Cl, Me), which undergo metallation to form
      [(POCOP)MCl] pincer complexes only under prolonged thermolysis. The formation of
      such cis,trans-dimers during pincer complex formation can be mitigated through
      the use of starting materials with more strongly binding ancillary ligands,
      improving the overall rate of ligand metallation. Carbonyl complexes of the type
      [(PCP)M(CO)](+) were synthesised from the pincer chloride complexes by halide
      abstraction, and displayed large nu(C-O) values, from 2170-2111 cm(-1),
      confirming the electron-poor nature of the compounds. The [(PCP)Pd(CO)](+)
      complexes also demonstrated the ability to reversibly bind carbon monoxide both
      in solution and the solid state, with the rate of decarbonylation increasing with
      increasing wavenumber for the C-O stretch.

PMID- 24737591
TI  - Synthesis of new thiobarbituric acid derived spiroheterobicyclic compounds and
      their antimicrobial activity.
AB  - A series pf novel (7S, 11R)-substituted diphenyl-2,4,8,10-tetraazaspiro [5.5]
      undecane-3-thio-1,5,9-triones 4a-j and (7S,11R)-substituted diphenyl-2,4,8,10
      tetraazaspiro[5.5] undecane-3-thio-1,5 dione, 9-thiones 5a-j were prepared using
      substituted aldehydes and urea/thiourea in the presence of thiobarbituric acid
      under solvent free, thermal and microwave conditions catalyzed by ecofriendly K
      10 clay. The antibacterial potency of these compounds in vitro on the gram
      negative strains Escherichia coli and Pseudomonas aeruginosa and gram positive
      strains Staphyllococcus aureus and Staphylococcus epidermidis was evaluated.

PMID- 24737593
TI  - Rapid analysis of phthalic acid esters in environmental water using fast elution
      gas chromatography with mass spectrometry and adaptive library spectra.
AB  - A method for the fast determination of the components in a complex sample by
      using gas chromatography with mass spectrometry was developed and used for the
      quantitative analysis of phthalic acid esters in environmental water. In the
      method, the adaptively corrected mass spectra were used to compensate for the
      differences between the library spectra and the measured ones in the experiment.
      The correction was obtained by the iterative transformation of the library
      spectra using iterative target transformation factor analysis, and the resolution
      was performed by non-negative immune algorithm using the corrected spectra. Rapid
      analysis of 16 phthalic acid esters in water samples was achieved using fast
      elution gas chromatography with mass spectrometry measurements. The results show
      that the mass spectra and chromatographic profiles of the phthalic acid esters
      can be obtained from the overlapping signal of 13 min elution, and accurate
      quantitative analysis can be obtained. The recoveries of the phthalic acid esters
      obtained by standard addition are between 90.3 and 107.4%, and the relative
      standard deviations obtained in repeated measurements are less than 9%. 

PMID- 24737594
TI  - Aging in place within permanent supportive housing.
AB  - OBJECTIVES: This study examined whether and how permanent supportive housing
      (PSH) programs are able to support aging in place among tenants with serious
      mental illness. DESIGN: Investigators used a mixed-method approach known as a
      convergent parallel design in which quantitative and qualitative data are
      analyzed separately and findings are merged during interpretation. Quantitative
      analysis compared 1-year pre-residential and post-residential outcomes for PSH
      program enrollees, comparing adults aged 35-49 years (n = 3990) with those aged
      50 years or older (n = 3086). Case study analysis using qualitative interviews
      with staff of a PSH program that exclusively served older adults identified
      challenges to providing support services. RESULTS: Substantial declines in days
      spent homeless and in justice system settings were found, along with increases in
      days living independently in apartments and in congregate settings. Homelessness
      and justice system involvement declined less for older adults than younger
      adults. Qualitative themes related to working with older adults included
      increased attention to medical vulnerability, residual effects of institutional
      care, and perceived preference for congregate living. CONCLUSIONS: PSH is an
      effective way to end homelessness, yet little is known about how programs can
      support housing stability among aging populations. Additional support and
      training for PSH staff will better promote successful aging in place.

PMID- 24737595
TI  - Douglas-fir plantations in Europe: a retrospective test of assisted migration to
      address climate change.
AB  - We evaluate genetic test plantations of North American Douglas-fir provenances in
      Europe to quantify how tree populations respond when subjected to climate regime
      shifts, and we examined whether bioclimate envelope models developed for North
      America to guide assisted migration under climate change can retrospectively
      predict the success of these provenance transfers to Europe. The meta-analysis is
      based on long-term growth data of 2800 provenances transferred to 120 European
      test sites. The model was generally well suited to predict the best performing
      provenances along north-south gradients in Western Europe, but failed to predict
      superior performance of coastal North American populations under continental
      climate conditions in Eastern Europe. However, model projections appear
      appropriate when considering additional information regarding adaptation of
      Douglas-fir provenances to withstand frost and drought, even though the model
      partially fails in a validation against growth traits alone. We conclude by
      applying the partially validated model to climate change scenarios for Europe,
      demonstrating that climate trends observed over the last three decades warrant
      changes to current use of Douglas-fir provenances in plantation forestry
      throughout Western and Central Europe. 

PMID- 24737596
TI  - Donor-acceptor-type copolymers based on a naphtho[1,2-c:5,6-c]bis(1,2,5
      thiadiazole) scaffold for high-efficiency polymer solar cells.
AB  - Four donor-acceptor-type low-bandgap conjugated polymers based on a naphtho[1,2
      c:5,6-c]bis(1,2,5-thiadiazole) (NT) acceptor and different donors bridged by a
      bithiophene spacer have been synthesized through Suzuki or Stille polymerization
      reactions. Fluorene (F), carbazole (Cz), alkylidene fluorene (AF), and
      benzodithiophene (BDT) were selected as the donor units to produce a series of
      new conjugated polymers. Owing to the different electron-donating ability of the
      donor units, the energy levels, absorption spectra, bandgaps, and carrier
      mobilities of the resulting polymers were systematically tuned. Bulk
      heterojunction-type polymer solar cells based on the new polymers and [6,6]
      phenyl-C61 -butyric acid methyl ester (PC61 BM) or [6,6]-phenyl-C71 -butyric acid
      methyl ester (PC71 BM) were investigated and all of the devices exhibited good
      photovoltaic performance, with power-conversion efficiencies (PCEs) over 3 %. The
      best device performance was achieved by PF-C12NT, with an open-circuit voltage
      (Voc ) of 0.87 V, a short-circuit current density (Jsc ) of 12.19 mA cm(-2) , a
      fill factor (FF) of 61.36 %, and a PCE of 6.51 % under simulated sunlight (100 mW
      cm(-2) , AM 1.5G). 

PMID- 24737597
TI  - A structural equation model of posttraumatic growth after prostate cancer.
AB  - BACKGROUND: Posttraumatic growth (PTG) encompasses an individual's perception of
      positive personal changes as a consequence of a traumatic incident. The current
      study tested a theoretical model of PTG with the inclusion of resilience in the
      context of cancer survivors. METHODS: Members of a prostate cancer support
      network were invited to complete a cross-sectional mail survey (N = 514, 52.8%
      response; mean age 70.17 years, and time since diagnosis 7.5 years). RESULTS:
      Challenge appraisal (beta = 0.361), examining core beliefs (beta = 0.474),
      intrusive rumination (beta = 0.130), and peer support factors (beta = 0.104) had
      significant direct effects on PTG. Resilience (beta = 0.164), challenge appraisal
      (beta = 0.215), distress (beta = 0.186), and examining core beliefs (beta =
      0.105) had significant indirect effects on PTG. CONCLUSIONS: Results support the
      notion that the appraisal of cancer, disruption of fundamental beliefs, and
      experience of intrusive cancer-related rumination are associated with PTG.
      Additionally, a sense of connection with peers and seeking an understanding of
      the cancer experience through peers is important for the perception of PTG.
      Possible indirect pathways were also proposed between resilience and PTG.

PMID- 24737598
TI  - The potential for bioaugmentation of sand filter materials from waterworks using
      bacterial cultures degrading 4-chloro-2-methylphenoxyacetic acid.
AB  - BACKGROUND: The herbicide 4-chloro-2-methylphenoxyacetic acid (MCPA) is found
      frequently in Danish groundwater in concentrations exceeding the EU threshold
      limit of 0.1 ug L(-1) . Groundwater is used for drinking water, and one potential
      remediation strategy is bioaugmentation using inoculation of sand filters at
      affected waterworks with degrader bacteria. Numerous bacteria degrading
      phenoxyacetic acid herbicide have previously been isolated, and they may be
      candidates for bioaugmentation processes. Designing the optimum inoculum,
      however, requires knowledge of the capacity for degrading realistically low
      herbicide concentrations and the robustness of the bacteria when inoculated into
      sand filter materials. RESULTS: Testing a range of different MCPA-mineralising
      bacterial combinations, using a high-throughput microplate radiorespirometric
      mineralisation assay, highlighted three efficient cocultures for mineralising low
      MCPA concentrations. Cocultures demonstrating a shorter time delay before
      initiation of (14) C-ring-labelled MCPA mineralisation to (14) CO2 , and a more
      extensive mineralisation of MCPA, compared with those of single strains, were
      found. When inoculated into different sand filter materials, the coculture effect
      was diminished, but several single strains enhanced MCPA mineralisation
      significantly at low MCPA concentrations. CONCLUSION: This study shows that an
      increase in the potential for mineralisation of low herbicide concentrations in
      sand filter materials can be achieved by inoculating with bacterial degrader
      cultures. (c) 2014 Society of Chemical Industry.

PMID- 24737599
TI  - Clinical outcome according to the level of preexisting epidermal growth factor
      receptor T790M mutation in patients with lung cancer harboring sensitive
      epidermal growth factor receptor mutations.
AB  - BACKGROUND: Epidermal growth factor receptor (EGFR) T790M mutation drives
      acquired drug resistance to EGFR tyrosine kinase inhibitors (EGFR-TKIs) in
      patients with EGFR-mutant lung cancer. However, it was reported that this
      mutation may exist before drug exposure. The objective of the current study was
      to evaluate whether the clinical outcomes are affected by the percentage of
      preexisting T790M mutations within a tumor. METHODS: Pretreatment tissues were
      collected from 124 patients with advanced non-small cell lung cancer with
      sensitizing EGFR mutations that were detected by direct sequencing. Genotyping
      for EGFR T790M mutation was further performed using matrix-assisted laser
      desorption/ionization time-of-flight mass spectrometry. Patients who were
      positive for the T790M mutation were divided to 2 subgroups according to T790M
      mutant signal frequency. RESULTS: The T790M mutation was found in 31 patients
      (25.0%). The T790M mutation frequency at which the risk of disease progression
      after therapy with EGFR-TKIs begins to increase was estimated to be 3.2%. The
      patients with T790M-positive tumors had a shorter time to disease progression
      after treatment with EGFR-TKIs (median, 6.3 months vs 11.5 months; P < .001) and
      overall survival (median, 16.1 months vs 26.5 months; P = .065) compared with
      those with T790M-negative tumors. Among the T790M-positive patients, the patients
      with high T790M frequency (9 patients) were found to have a shorter time to
      disease progression (median, 2.4 months vs 6.7 months; P = .009) and overall
      survival (median, 9.1 months vs 18.7 months; P = .018) compared with those with
      low T790M frequency (22 patients). CONCLUSIONS: A preexisting EGFR T790M mutation
      was noted in 25% of patients with EGFR-mutant lung cancer. Patients with a high
      T790M mutation frequency had worse clinical outcomes to EGFR-TKIs than patients
      with a low T790M mutation frequency.

PMID- 24737601
TI  - Development of a new contactless dielectrophoresis system for active particle
      manipulation using movable liquid electrodes.
AB  - This study presents a new DEP manipulation technique using a movable liquid
      electrode, which allows manipulation of particles by actively controlling the
      locations of electrodes and applying on-off electric input signals. This DEP
      system consists of mercury as a movable liquid electrode, indium tin oxide (ITO)
      coated glass, SU-8-based microchannels for electrode passages, and a PDMS medium
      chamber. A simple squeezing method was introduced to build a thin PDMS layer at
      the bottom of the medium chamber to create a contactless DEP system. To determine
      the operating conditions, the DEP force and the friction force were analytically
      compared for a single cell. In addition, an appropriate frequency range for
      effective DEP manipulation was chosen based on an estimation of the Clausius
      Mossotti factor and the effective complex permittivity of the yeast cell using
      the concentric shell model. With this system, we demonstrated the active
      manipulation of yeast cells, and measured the collection efficiency and the
      dielectrophoretic velocity of cells for different AC electric field strengths and
      applied frequencies. The experimental results showed that the maximum collection
      efficiency reached was approximately 90%, and the dielectrophoretic velocity
      increased with increasing frequency and attained the maximum value of 10.85 +/-
      0.95 MUm/s at 100 kHz, above which it decreased.

PMID- 24737602
TI  - Mouse matrix metalloprotease-1a (Mmp1a) gives new insight into MMP function.
AB  - Matrix metalloprotease-1 (MMP1) has been implicated in many human disease
      processes, however the lack of a well characterized murine homologue has
      significantly limited the study of MMP1 and the development of MMP-targeted
      therapeutics. The discovery of murine Mmp1a in 2001, the functional mouse
      homologue of MMP1, offers a valuable tool for modeling MMP1-mediated processes in
      mice. Variation in physiologic expression levels of Mmp1a in mice as compared to
      MMP1 in humans highlights the importance of understanding the similarities and
      differences between the homologues. Recent studies have demonstrated tumor growth
      , invasion-, and angiogenesis-promoting functions of Mmp1a in lung cancer models,
      consistent with the analogous functions observed for human MMP1. Biochemical
      investigations have shown that point mutations in the pro-domain of mouse Mmp1a
      weaken docking between the pro- and catalytic domains, generating an unstable
      zymogen primed for activation. The difficulty to effectively maintain Mmp1a in
      the zymogen form may account for the tight control of Mmp1a expression and
      reduced expression in normal tissue as compared to inflammatory states or cancer.
      This discovery raises important questions about the activation mechanisms and
      regulation of the MMP family in general.

PMID- 24737603
TI  - WITHDRAWN: Psychosocial treatment for opiate abuse and dependence.

PMID- 24737604
TI  - Informing conservation management about structural versus functional
      connectivity: a case-study of Cross River gorillas.
AB  - Connectivity among subpopulations is vital for the persistence of small and
      fragmented populations. For management interventions to be effective conservation
      planners have to make the critical distinction between structural connectivity
      (based on landscape structure) and functional connectivity (which considers both
      landscape structure and organism-specific behavioral attributes) which can differ
      considerably within a given context. We assessed spatial and temporal changes in
      structural and functional connectivity of the Cross River gorilla Gorilla gorilla
      diehli (CRG) population in a 12,000 km(2) landscape in the Nigeria-Cameroon
      border region over a 23-year period, comparing two periods: 1987-2000 and 2000
      2010. Despite substantial forest connections between occupied areas, genetic
      evidence shows that only limited dispersal occurs among CRG subpopulations. We
      used remotely sensed land-cover data and simulated human pressure (using a
      spatially explicit agent-based model) to assess human impact on connectivity of
      the CRG population. We calculated cost-weighted distances between areas occupied
      by gorillas as measures of connectivity (structural based on land-cover only,
      functional based on both land-cover and simulated human pressure). Whereas
      structural connectivity decreased by 5% over the 23-year period, functional
      connectivity decreased by 11%, with both decreasing more during the latter
      compared to the earlier period. Our results highlight the increasing threat of
      isolation of CRG subpopulations due to human disturbance, and provide insight
      into how increasing human influence may lead to functional isolation of wildlife
      populations despite habitat continuity, a pressing and common issue in tropical
      Africa often not accounted for when deciding management interventions. In
      addition to quantifying threats to connectivity, our study provides crucial
      evidence for management authorities to identify actions that are more likely to
      be effective for conservation of species in human-dominated landscapes. Our
      approach can be easily applied to other species, regions, and scales.

PMID- 24737600
TI  - The role of viral persistence in flavivirus biology.
AB  - In nature, vector-borne flaviviruses are persistently cycled between either the
      tick or mosquito vector and small mammals such as rodents, skunks, and swine.
      These viruses account for considerable human morbidity and mortality worldwide.
      Increasing and substantial evidence of viral persistence in humans, which
      includes the isolation of RNA by RT-PCR and infectious virus by culture,
      continues to be reported. Viral persistence can also be established in vitro in
      various human, animal, arachnid, and insect cell lines in culture. Although some
      research has focused on the potential roles of defective virus particles, evasion
      of the immune response through the manipulation of autophagy and/or apoptosis,
      the precise mechanism of flavivirus persistence is still not well understood. We
      propose additional research for further understanding of how viral persistence is
      established in different systems. Avenues for additional studies include
      determining whether the multifunctional flavivirus protein NS5 has a role in
      viral persistence, the development of relevant animal models of viral
      persistence, and investigating the host responses that allow vector-borne
      flavivirus replication without detrimental effects on infected cells. Such
      studies might shed more light on the viral-host relationships and could be used
      to unravel the mechanisms for establishment of persistence. 

PMID- 24737605
TI  - Stabilisation of 2,6-diarylpyridinium cation by through-space polar-pi
      interactions.
AB  - The through-space polar-pi interactions between pyridinium ion and the adjacent
      aromatic rings in 2,6-diarylpyridines affect the pKa values. Hammett analysis
      illustrates that the basicity of pyridines correlates well with the sigma values
      of the substituents at the para position of the flanking aryl rings.

PMID- 24737606
TI  - Attitudes regarding privacy of genomic information in personalized cancer
      therapy.
AB  - OBJECTIVE: To evaluate attitudes regarding privacy of genomic data in a sample of
      patients with breast cancer. METHODS: Female patients with breast cancer (n=100)
      completed a questionnaire assessing attitudes regarding concerns about privacy of
      genomic data. RESULTS: Most patients (83%) indicated that genomic data should be
      protected. However, only 13% had significant concerns regarding privacy of such
      data. Patients expressed more concern about insurance discrimination than
      employment discrimination (43% vs 28%, p<0.001). They expressed less concern
      about research institutions protecting the security of their molecular data than
      government agencies or drug companies (20% vs 38% vs 44%; p<0.001). Most did not
      express concern regarding the association of their genomic data with their name
      and personal identity (49% concerned), billing and insurance information (44%
      concerned), or clinical data (27% concerned). Significantly fewer patients were
      concerned about the association with clinical data than other data types
      (p<0.001). In the absence of direct benefit, patients were more willing to
      consent to sharing of deidentified than identified data with researchers not
      involved in their care (76% vs 60%; p<0.001). Most (85%) patients were willing to
      consent to DNA banking. DISCUSSION: While patients are opposed to indiscriminate
      release of genomic data, privacy does not appear to be their primary concern.
      Furthermore, we did not find any specific predictors of privacy concerns.
      CONCLUSIONS: Patients generally expressed low levels of concern regarding privacy
      of genomic data, and many expressed willingness to consent to sharing their
      genomic data with researchers.

PMID- 24737607
TI  - A comparative analysis of methods for predicting clinical outcomes using high
      dimensional genomic datasets.
AB  - OBJECTIVE: The objective of this investigation is to evaluate binary prediction
      methods for predicting disease status using high-dimensional genomic data. The
      central hypothesis is that the Bayesian network (BN)-based method called
      efficient Bayesian multivariate classifier (EBMC) will do well at this task
      because EBMC builds on BN-based methods that have performed well at learning
      epistatic interactions. METHOD: We evaluate how well eight methods perform binary
      prediction using high-dimensional discrete genomic datasets containing epistatic
      interactions. The methods are as follows: naive Bayes (NB), model averaging NB
      (MANB), feature selection NB (FSNB), EBMC, logistic regression (LR), support
      vector machines (SVM), Lasso, and extreme learning machines (ELM). We use a
      hundred 1000-single nucleotide polymorphism (SNP) simulated datasets, ten 10,000
      SNP datasets, six semi-synthetic sets, and two real genome-wide association
      studies (GWAS) datasets in our evaluation. RESULTS: In fivefold cross-validation
      studies, the SVM performed best on the 1000-SNP dataset, while the BN-based
      methods performed best on the other datasets, with EBMC exhibiting the best
      overall performance. In-sample testing indicates that LR, SVM, Lasso, ELM, and NB
      tend to overfit the data. DISCUSSION: EBMC performed better than NB when there
      are several strong predictors, whereas NB performed better when there are many
      weak predictors. Furthermore, for all BN-based methods, prediction capability did
      not degrade as the dimension increased. CONCLUSIONS: Our results support the
      hypothesis that EBMC performs well at binary outcome prediction using high
      dimensional discrete datasets containing epistatic-like interactions. Future
      research using more GWAS datasets is needed to further investigate the potential
      of EBMC.

PMID- 24737608
TI  - State of the science in cervical cancer: where we are today and where we need to
      go.
AB  - Invasive cervical cancer remains an important global cause of death, despite the
      declining prevalence within the United States. Definitive therapies, including
      surgical resection of early-stage disease and chemoradiation for locally advanced
      disease, can be curative. For women who experience local or distant recurrences,
      the prognosis remains poor and better treatments are required. On July 18, 2013,
      The Gynecologic Oncology Group sponsored a State of the Science in Cervical
      Cancer Symposium with experts, researchers, clinicians, and interested
      stakeholders. This article summarize the progress that has been made, questions
      that require further investigation, and contemporary genomic findings and
      innovative treatments that may help inform the next generation of clinical trials
      for patients with cervical cancer.

PMID- 24737609
TI  - Trauma symptoms of individuals with mental illness at risk for homelessness
      participating in a life skills intervention.
AB  - This study investigated 1) trauma symptom changes following the implementation of
      a life skills intervention; 2) the relationship between demographic
      characteristics, cognitive functioning, life skill knowledge and changes in
      trauma symptoms; and 3) predictive factors of trauma symptoms during housing
      transitions. Participants (N=72) enrolled in intervention modules to increase
      residential stability (room and self-care, money management, nutrition management
      or safe community participation), completed the Impact of Event Scale-Revised,
      ACLS-2000 and a Practical Skills Test at baseline, post-intervention and 3 and 6
      months later to examine differences in trauma symptoms and treatment outcomes.
      Trauma symptoms were highest at baseline and decreased significantly for most
      participants over time. For a subgroup of females experiencing abuse and
      individuals who were homeless less than 1 year, there was an increase in symptoms
      at 3 months post-intervention (highest rate of housing transition). This small
      convenience sample represents a limited geographic area. Replication of the study
      with larger groups for generalization, and further investigation into the
      specific impact of symptoms on function were recommended for future research.

PMID- 24737610
TI  - The influence of context: a naturalistic study of Ugandan children's doings in
      outdoor spaces.
AB  - The purpose of this study was to explore children's everyday outdoor occupations
      in context. A naturalistic observational approach was employed to record the
      observed outdoor occupations of children in Mbarara, Uganda. Thematic analysis,
      through pattern formation and constant comparative analysis, was used to uncover
      categories and themes in the data. Patterns emerged from the data revealing two
      overarching categories containing three themes: 1) types of occupations: play,
      work and nothing in particular and 2) characteristics of occupational engagement:
      being in peer groups, having fun and using materials in the environment. The
      themes reveal that children's occupations are both similar and different across
      minority and majority world cultures and that children's occupations are
      contextually situated and flexible in nature. A limitation of the study was that
      the observational approach made identification of children's ages subjective.
      Subsequent studies should explore children's experiences of occupational
      engagement using interviews and focus groups.

PMID- 24737611
TI  - Fetal alcohol syndrome surveillance: age of syndrome manifestation in case
      ascertainment.
AB  - BACKGROUND: Fetal alcohol syndrome (FAS) is a leading cause of developmental
      disability (Abel & Sokol, ). Active public health surveillance through medical
      record abstraction has been used to estimate FAS prevalence rates, typically
      based on birth cohorts. There is an extended time for FAS characteristics to
      become apparent in infants and young children, and there are often delays in
      syndrome recognition and documentation. This methodological study analyzes the
      age at case ascertainment in a large surveillance program. METHODS: The Fetal
      Alcohol Syndrome Surveillance (FASSLink) Project, funded by the Centers for
      Disease Control and Prevention, sought to estimate FAS prevalence rates in eight
      U.S. states. FASSLink used linked abstractions from multiple health care records
      of suspected cases of FAS. The present study analyzed data from this effort to
      determine the child's age in months at confirming abstraction. RESULTS: The
      average age at abstraction for confirmed/probable FAS cases (n = 422) was 48.3
      (+/-19.5) months with a range of 0 to 94 months. Age of ascertainment varied by
      state and decreased with each birth year; the number of cases ascertained also
      decreased in a steep stepwise gradient over the 6 birth years in the study.
      CONCLUSION: FAS surveillance efforts should screen records of children who are
      much older than is typical in birth defects surveillance. To best establish rates
      of FAS using medical records abstraction, surveillance efforts should focus on 1
      year birth cohorts followed for a fixed number of years or, if using multi-year
      cohorts, should implement staggered end dates allowing all births to be followed
      for up to 8 years of age.

PMID- 24737613
TI  - Fatigue in stroke rehabilitation patients: a pilot study.
AB  - BACKGROUND AND PURPOSE: Stroke is the leading cause of adult disability.
      Rehabilitation is a vital component of post-stroke care with two-thirds of
      survivors requiring rehabilitation. Fatigue is a common issue affecting stroke
      patients and is a barrier to rehabilitation causing inefficient care provision
      and potential limitation to patient recovery. No study to date has investigated
      whether the experience of fatigue is different between the two main causes of
      ischemic stroke: small-vessel (SVD) and large-vessel disease (LVD). The aim of
      the present study is to complete a pilot study to inform the feasibility, design,
      magnitude of difference in experience of fatigue, and sample size for a
      definitive study to evaluate differences in fatigue between these two groups of
      stroke patients. The experimental hypothesis is that participants with LVD
      experience a significantly greater level of fatigue than those with SVD as
      assessed by the Fatigue Severity Scale (FSS). METHODS: The study used a cohort
      observational design. Thirteen participants were recruited over a two-month
      period from King's College Hospital. Participants were visited on average at the
      start of the second week of rehabilitation to complete the FSS. An independent t
      test and ANCOVA were performed. For all statistical analyses, a significance
      level of p<0.05 was used. RESULTS: The study demonstrated a trend towards LVD
      participants reporting higher fatigue scores than SVD participants, even when
      controlling for age, with gender having no confounding effect. CONCLUSIONS:
      Fatigue is common amongst ischemic stroke rehabilitation participants with 85% of
      the combined sample experiencing fatigue at the start of the second week. The
      results demonstrate a trend towards LVD participants experiencing greater
      fatigue. While the results were non-significant, the study demonstrates a
      feasible methodology which could help lay the groundwork for future research.

PMID- 24737612
TI  - Demographic characteristics do not decrease the utility of depressive symptoms
      assessments: examining the practical impact of item bias in four heterogeneous
      samples of older adults.
AB  - OBJECTIVE: Previous studies have identified differential item function (DIF) in
      depressive symptoms measures, but the impact of DIF has been rarely reported.
      Given the critical importance of depressive symptoms assessment among older
      adults, we examined whether DIF due to demographic characteristics resulted in
      salient score changes in commonly used measures. METHODS: Four longitudinal
      studies of cognitive aging provided a sample size of 3754 older adults and
      included individuals both with and without a clinical diagnosis of major
      depression. Each study administered at least one of the following measures: the
      Center for Epidemiologic Studies Depression scale (20-item ordinal response or 10
      item dichotomous response versions), the Geriatric Depression Scale, and the
      Montgomery-Asberg Depression Rating Scale. Hybrid logistic regression-item
      response theory methods were used to examine the presence and impact of DIF due
      to age, sex, race/ethnicity, and years of education on the depressive symptoms
      items. RESULTS: Although statistically significant DIF due to demographic factors
      was present on several items, its cumulative impact on depressive symptoms scores
      was practically negligible. CONCLUSIONS: The findings support substantive
      meaningfulness of previously reported demographic differences in depressive
      symptoms among older adults, showing that these individual differences were
      unlikely to have resulted from item bias attributable to demographic
      characteristics we examined.

PMID- 24737614
TI  - On-line immunoaffinity solid-phase extraction capillary electrophoresis mass
      spectrometry for the analysis of large biomolecules: a preliminary report.
AB  - The analysis of large biomolecules by on-line immunoaffinity solid-phase
      extraction capillary electrophoresis mass spectrometry (IA-SPE-CE-MS) remains
      unexplored because of the complex issues that need to be addressed. In this
      preliminary study, we used the human glycoprotein transferrin (Tf) as a model of
      a large biomolecule. First, we established by CE-UV a novel method compatible
      with IA-SPE-CE-MS, based on the use of a fused silica capillary coated with an
      anionic derivative of polyacrylamide (UltraTrol(TM) Dynamic Pre-Coat High Normal,
      HN) to prevent protein adsorption. The methodology allowed the detection of the
      most abundant Tf sialoforms. Repeatability studies demonstrated high stability of
      the coated capillaries, which was required for on-line immunoextraction and MS
      detection. IA-SPE-CE-UV and IA-SPE-CE-MS methods were optimized for the analysis
      of Tf standards and human serum samples using a laboratory-made IA sorbent. Three
      peaks corresponding to Tf were detected with UV detection when on-line
      immunoextraction was applied to the standards. The use of MS detection, however,
      reduced the resolution of the electrophoretic separation. Finally, we
      demonstrated that it was possible to detect Tf in human serum samples, after off
      line serum sample de-salting by centrifugal filtration. 

PMID- 24737615
TI  - Designed single-step synthesis, structure, and derivative textural properties of
      well-ordered layered penta-coordinate silicon alcoholate complexes.
AB  - The controllable synthesis of well-ordered layered materials with specific
      nanoarchitecture poses a grand challenge in materials chemistry. Here the
      solvothermal synthesis of two structurally analogous 5-coordinate organosilicate
      complexes through a novel transesterification mechanism is reported. Since the
      polycrystalline nature of the intrinsic hypervalent Si complex thwarts the
      endeavor in determining its structure, a novel strategy concerning the elegant
      addition of a small fraction of B species as an effective crystal growth mediator
      and a sacrificial agent is proposed to directly prepare diffraction-quality
      single crystals without disrupting the intrinsic elemental type. In the
      determined crystal structure, two monomeric primary building units (PBUs) self
      assemble into a dimeric asymmetric secondary BU via strong Na(+)-O(2-) ionic
      bonds. The designed one-pot synthesis is straightforward, robust, and efficient,
      leading to a well-ordered (10i)-parallel layered Si complex with its principal
      interlayers intercalated with extensive van der Waals gaps in spite of the
      presence of substantial Na(+) counter-ions as a result of unique atomic
      arrangement in its structure. However, upon fast pyrolysis, followed by acid
      leaching, both complexes are converted into two SiO2 composites bearing BET
      surface areas of 163.3 and 254.7 m(2)  g(-1) for the pyrolyzed intrinsic and B
      assisted Si complexes, respectively. The transesterification methodology merely
      involving alcoholysis but without any hydrolysis side reaction is designed to
      have generalized applicability for use in synthesizing new layered metal-organic
      compounds with tailored PBUs and corresponding metal oxide particles with
      hierarchical porosity.

PMID- 24737616
TI  - A base-free neutral phase-transfer reaction system.
AB  - Although phase-transfer reactions catalyzed by using quaternary ammonium salts
      are generally believed to require base additives, we discovered that, even
      without any base additives, conjugate additions of 3-substituted oxindoles to
      nitroolefins proceeded smoothly in the presence of lipophilic quaternary ammonium
      bromide under water-organic biphasic conditions. The mechanism of this novel base
      free neutral phase-transfer reaction system is investigated and the assumed
      catalytic cycle is presented together with interesting effects of water and
      lipophilicity of the phase-transfer catalyst. The base-free neutral phase
      transfer reaction system can be applied to highly enantioselective conjugate
      addition and aldol reactions under the influence of chiral bifunctional ammonium
      bromides as key catalysts. The structure of the chiral ammonium enolate
      intermediate is discussed based on the single-crystal X-ray structures of
      relevant ammonium salts and the importance of bifunctional design of catalyst is
      clearly explained in the model of intermediate. 

PMID- 24737617
TI  - Self-organization of neural tissue architectures from pluripotent stem cells.
AB  - Despite being a subject of intensive research, the mechanisms underlying the
      formation of neural tissue architectures during development of the central
      nervous system remain largely enigmatic. So far, studies into neural pattern
      formation have been restricted mainly to animal experiments. With the advent of
      pluripotent stem cells it has become possible to explore early steps of nervous
      system development in vitro. These studies have unraveled a remarkable propensity
      of primitive neural cells to self-organize into primitive patterns such as neural
      tube-like rosettes in vitro. Data from more advanced 3D culture systems indicate
      that this intrinsic propensity for self-organization can even extend to the
      formation of complex architectures such as a multilayered cortical
      neuroepithelium or an entire optic cup. These novel experimental paradigms not
      only demonstrate the enormous self-organization capacity of neural stem cells,
      they also provide exciting prospects for studying the earliest steps of human
      neural tissue development and the pathogenesis of brain malformations in
      reductionist in vitro paradigms.

PMID- 24737618
TI  - Simple enrichment of thiol-containing biomolecules by using zinc(II)-cyclen
      functionalized magnetic beads.
AB  - A simple and efficient method based on magnetic-bead technology has been
      developed for the enrichment of thiol-containing biomolecules, such as l
      glutathione and cysteine-containing peptides. The thiol-binding site on the bead
      is a mononuclear complex of zinc(II) with 1,4,7,10-tetraazacyclododecane
      (cyclen); this is linked to a hydrophilic cross-linked agarose coating on a
      particle that has a magnetic core. All steps for the thiol-affinity separation
      are conducted in aqueous buffers with 0.10 mL of the magnetic beads in a 1.5 mL
      microtube. The entire separation protocol for thiol-containing compounds, from
      addition to elution, requires less than one hour per sample, provided the buffers
      and the zinc(II)-cyclen-functionalized magnetic beads have been prepared in
      advance. The thiol-affinity magnetic beads are reusable at least 15 times without
      a decrease in their thiol-binding ability, and they are stable for six months at
      room temperature. 

PMID- 24737620
TI  - Anxiety in common situations of everyday life in breast cancer survivors.

PMID- 24737621
TI  - Stochastic variation in network epidemic models: implications for the design of
      community level HIV prevention trials.
AB  - Important sources of variation in the spread of HIV in communities arise from
      overlapping sexual networks and heterogeneity in biological and behavioral risk
      factors in populations. These sources of variation are not routinely accounted
      for in the design of HIV prevention trials. In this paper, we use agent-based
      models to account for these sources of variation. We illustrate the approach with
      an agent-based model for the spread of HIV infection among men who have sex with
      men in South Africa. We find that traditional sample size approaches that rely on
      binomial (or Poisson) models are inadequate and can lead to underpowered studies.
      We develop sample size and power formulas for community randomized trials that
      incorporate estimates of variation determined from agent-based models. We
      conclude that agent-based models offer a useful tool in the design of HIV
      prevention trials.

PMID- 24737622
TI  - Synthesis and characterization of Ni(III)N3S2 complexes as active site models for
      the oxidized form of nickel superoxide dismutase.
AB  - Nickel complexes, [Ni(H2BA(R)TPP)](ClO4)2 (R = Ph for 1 or iPr for 2), supported
      by a pentadentate ligand H2BA(R)TPP were synthesized and oxidized to form Ni(III)
      species having a N3S2 coordination environment to mimic the active site of the
      oxidized form of nickel superoxide dismutase (NiSODox). The Ni(III) species 2(+)
      exhibited a rhombic signal with g values at 2.15, 2.12 and 2.02 similar to that
      of NiSODox. DFT calculations revealed that 2(+) has an unpaired electron
      primarily located in the dz2 orbital of the Ni(III) center, which strongly
      overlaps with the pz orbital of the axial pyridine nitrogen of H2BA(Pr)TPP.

PMID- 24737619
TI  - Mimicking the host and its microenvironment in vitro for studying mucosal
      infections by Pseudomonas aeruginosa.
AB  - Why is a healthy person protected from Pseudomonas aeruginosa infections, while
      individuals with cystic fibrosis or damaged epithelium are particularly
      susceptible to this opportunistic pathogen? To address this question, it is
      essential to thoroughly understand the dynamic interplay between the host
      microenvironment and P. aeruginosa. Therefore, using model systems that represent
      key aspects of human mucosal tissues in health and disease allows recreating in
      vivo host-pathogen interactions in a physiologically relevant manner. In this
      review, we discuss how factors of mucosal tissues, such as apical-basolateral
      polarity, junctional complexes, extracellular matrix proteins, mucus,
      multicellular complexity (including indigenous microbiota), and other
      physicochemical factors affect P. aeruginosa pathogenesis and are thus important
      to mimic in vitro. We highlight in vitro cell and tissue culture model systems of
      increasing complexity that have been used over the past 35 years to study the
      infectious disease process of P. aeruginosa, mainly focusing on lung models, and
      their respective advantages and limitations. Continued improvements of in vitro
      models based on our expanding knowledge of host microenvironmental factors that
      participate in P. aeruginosa pathogenesis will help advance fundamental
      understanding of pathogenic mechanisms and increase the translational potential
      of research findings from bench to the patient's bedside.

PMID- 24737623
TI  - Use of short chain alkyl imidazolium ionic liquids for on-line stacking and
      sweeping of methotrexate, flinic acid and folic acid: their application to
      biological fluids.
AB  - Methotrexate (MTX) is widely used for the treatment of many types of cancer.
      Folinic acid (FNA) and folic acid (FA) were usually simultaneously supplemented
      with MTX to reduce the side effects of a folate deficiency. This study, for the
      first time, included on-line sample preconcentration by stacking and sweeping
      techniques under reduced or enhanced electric conductivity in the sample region
      using short chain alkyl imidazolium ionic liquids (ILs) as micelle forming agents
      for analyte focusing. Both analyte focusing by micelle collapse (AFMC) and
      sweeping-MEKC had been investigated for the comparison of their effectiveness to
      examine simultaneously MTX, FNA and FA in plasma and urine under physiological
      conditions. In sweeping-MEKC, the sample solution without micelles was
      hydrodynamically injected as a long plug into a fused-silica capillary pre-filled
      with phosphate buffer containing 3.0 mol/L of 1-butyl-3-methylimidazolium bromide
      (BMIMBr). Using AFMC, the analytes were prepared in BMIMBr micellar matrix and
      hydrodynamically injected into the phosphate buffer without IL micelles. The
      conductivity ratio between BGE and sample (gamma, BGE/sample) was optimized to be
      3.0 in sweeping-MEKC and 0.33 in AFMC resulting the adequate separation of
      analytes within 4.0 min. To reduce the possibility of BMIMBr adsorption, an
      appropriate rinsing protocol was used. The limits of detection were calculated as
      0.1 ng/mL MTX, 0.05 ng/mL FNA and 0.05 ng/mL FA by sweeping-MEKC and 0.5 ng/mL
      MTX, 0.3 ng/mL FNA and 0.3 ng/mL FA by AFMC. The accuracy was tested by recovery
      in plasma and urine matrices giving values ranging between 90 and 110%. Both
      stacking and sweeping by BMIMBr could be successfully used for the rapid,
      selective and sensitive determination of pharmaceuticals in complex matrices due
      to its fascinating properties, including high conductivity, good thermal
      stability and ability to form different types of interactions by electrostatic,
      hydrophobic, hydrogen bonding and pi-pi interactions. In sweeping-MEKC, the using
      of BMIMBr enhanced the gamma factor, k retention factor and the injected amount
      of sample. Consequently, this technique offers particular potential for higher
      sensitivity by giving 22- and 5-fold sensitivity enhancement factors (SEFs) of
      MTX compared to CZE and AFMC, respectively.

PMID- 24737625
TI  - Listening to Religious Music and Mental Health in Later Life.
AB  - PURPOSE OF THE STUDY: Research has linked several aspects of religion--including
      service attendance, prayer, meditation, religious coping strategies,
      congregational support systems, and relations with God, among others--with
      positive mental health outcomes among older U.S. adults. This study examines a
      neglected dimension of religious life: listening to religious music. DESIGN AND
      METHODS: Two waves of nationally representative data on older U.S. adults were
      analyzed (n = 1,024). RESULTS: Findings suggest that the frequency of listening
      to religious music is associated with a decrease in death anxiety and increases
      in life satisfaction, self-esteem, and a sense of control across the 2 waves of
      data. In addition, the frequency of listening to gospel music (a specific type of
      religious music) is associated with a decrease in death anxiety and an increase
      in a sense of control. These associations are similar for blacks and whites,
      women and men, and low- and high-socioeconomic status individuals. IMPLICATIONS:
      Religion is an important socioemotional resource that has been linked with
      desirable mental health outcomes among older U.S. adults. This study shows that
      listening to religious music may promote psychological well-being in later life.
      Given that religious music is available to most individuals--even those with
      health problems or physical limitations that might preclude participation in more
      formal aspects of religious life--it might be a valuable resource for promoting
      mental health later in the life course.

PMID- 24737626
TI  - Does End-of-Life Planning Help Partners Become Better Surrogates?
AB  - PURPOSE OF THE STUDY: This study investigates the role of surrogates' involvement
      in their partners' end-of-life care planning, focusing on the relationship
      between the extent and type of end-of-life planning in which surrogates have been
      involved and the accuracy of their substituted judgments. DESIGN AND METHODS: The
      data come from an internet survey collected by Knowledge Networks and the
      National Center for Family and Marriage Research. The national sample is
      comprised of 1,075 opposite-sex American couples aged 18-64. A series of
      multilevel negative binomial regression analyses were conducted. RESULTS:
      Surrogates' involvement in multiple types of planning helped them to make
      accurate substituted judgments, whereas surrogates' involvement in informal
      discussions helped them to make accurate estimations primarily when they wanted
      limited care for themselves. IMPLICATIONS: This study highlights the importance
      of engaging in both advance directives and informal discussion. The findings also
      suggest that surrogates who want extensive care for themselves may need extra
      attention when practitioners assist them in making a substituted judgment.

PMID- 24737627
TI  - Identification of new bacterial and fungal pathogens on surveillance bronchoscopy
      prior to sinus surgery in patients with cystic fibrosis.
AB  - BACKGROUND: Flexible fiberoptic bronchoscopy was performed prior to functional
      endoscopic sinus surgery (FESS) while under general anesthesia to collect
      bronchoalveolar lavage fluid (BALF) for lower respiratory tract cultures in
      patients with cystic fibrosis (CF). METHODS: A retrospective chart review was
      performed on all CF patients who underwent combined FESS and bronchoscopy between
      January 2009 and October 2010. Along with demographic data, bacterial, fungal,
      and acid fast bacillus culture data from BALF was collected and compared to
      oropharyngeal swab and sputum cultures obtained over the year prior to FESS and
      bronchoscopy. RESULTS: A total of 77 patients were enrolled with mean age 12.5 +/
      SD 6.5 (range 2-29) years. Mean FEV1 was 86% +/-18.4 (range 33-128) % of
      predicted. Patients averaged 6.5 (range 1-13) sputum or OP cultures in the year
      prior to FESS. BALF cultures identified a new bacterial pathogen in 19% (n=15) of
      patients, which altered antibiotic regimen immediately in two patients and sub
      acutely in five patients. BALF cultures identified a new fungal pathogen in 42%
      (n=32) of patients, which resulted in the addition of antifungal therapy in eight
      patients. BALF cultures did not identify previously undetected AFB culture
      positive patients. No significant differences were found between patients with
      and without new discoveries of bacterial or fungal pathogens with regards to key
      clinical demographic data, lung function parameters, healthcare utilization, or
      need for antibiotics over the year prior to FESS. There was no relationship
      between the total number of respiratory cultures obtained in the year prior to
      bronchoscopy and the identification of new bacterial or fungal pathogens.
      CONCLUSIONS: Surveillance BALF cultures obtained prior to FESS identified
      bacterial and fungal pathogens not previously detected by sputum or OP swab
      cultures in a cohort of CF patients with chronic sinus disease. Moreover, the
      identification of these new pathogens altered clinical management in a small
      number of patients.

PMID- 24737624
TI  - A general principle governs vision-dependent dendritic patterning of retinal
      ganglion cells.
AB  - Dendritic arbors of retinal ganglion cells (RGCs) collect information over a
      certain area of the visual scene. The coverage territory and the arbor density of
      dendrites determine what fraction of the visual field is sampled by a single cell
      and at what resolution. However, it is not clear whether visual stimulation is
      required for the establishment of branching patterns of RGCs, and whether a
      general principle directs the dendritic patterning of diverse RGCs. By analyzing
      the geometric structures of RGC dendrites, we found that dendritic arbors of RGCs
      underwent a substantial spatial rearrangement after eye-opening. Light
      deprivation blocked both the dendritic growth and the branch patterning,
      suggesting that visual stimulation is required for the acquisition of specific
      branching patterns of RGCs. We further showed that vision-dependent dendritic
      growth and arbor refinement occurred mainly in the middle portion of the
      dendritic tree. This nonproportional growth and selective refinement suggest that
      the late-stage dendritic development of RGCs is not a passive stretching with the
      growth of eyes, but rather an active process of selective growth/elimination of
      dendritic arbors of RGCs driven by visual activity. Finally, our data showed that
      there was a power law relationship between the coverage territory and dendritic
      arbor density of RGCs on a cell-by-cell basis. RGCs were systematically less
      dense when they cover larger territories regardless of their cell type, retinal
      location, or developmental stage. These results suggest that a general structural
      design principle directs the vision-dependent patterning of RGC dendrites.

PMID- 24737628
TI  - Graphene oxide as a micro-solid-phase extraction sorbent for the enrichment of
      parabens from water and vinegar samples.
AB  - A simple hydrophilic polyamide organic membrane protected micro-solid-phase
      extraction method with graphene oxide as the sorbent was developed for the
      enrichment of some parabens from water and vinegar samples prior to gas
      chromatography with mass spectrometry detection. The main experimental parameters
      affecting the extraction efficiencies, such as the type and amount of the
      sorbent, extraction time, stirring rate, salt addition, sample solution pH and
      desorption conditions, were investigated. Under the optimized experimental
      conditions, the method showed a good linearity in the range of 0.1-100.0 ng/mL
      for water samples and 0.5-100.0 ng/mL for vinegar samples, with the correlation
      coefficients varying from 0.9978 to 0.9997. The limits of detection (S/N = 3) of
      the method were in the range of 0.005-0.010 ng/mL for water samples and 0.01-0.05
      ng/mL for vinegar samples, respectively. The recoveries of the method for the
      analytes at spiking levels of 5.0 and 70.0 ng/mL were between 84.6 and 106.4%
      with the relative standard deviations varying from 4.2 to 9.5%. The results
      indicated that the developed method could be a practical approach for the
      determination of paraben residues in water and vinegar samples. 

PMID- 24737629
TI  - Mass spectrometry of peptides and proteins from human blood.
AB  - It is difficult to convey the accelerating rate and growing importance of mass
      spectrometry applications to human blood proteins and peptides. Mass spectrometry
      can rapidly detect and identify the ionizable peptides from the proteins in a
      simple mixture and reveal many of their post-translational modifications.
      However, blood is a complex mixture that may contain many proteins first
      expressed in cells and tissues. The complete analysis of blood proteins is a
      daunting task that will rely on a wide range of disciplines from physics,
      chemistry, biochemistry, genetics, electromagnetic instrumentation, mathematics
      and computation. Therefore the comprehensive discovery and analysis of blood
      proteins will rank among the great technical challenges and require the
      cumulative sum of many of mankind's scientific achievements together. A variety
      of methods have been used to fractionate, analyze and identify proteins from
      blood, each yielding a small piece of the whole and throwing the great size of
      the task into sharp relief. The approaches attempted to date clearly indicate
      that enumerating the proteins and peptides of blood can be accomplished. There is
      no doubt that the mass spectrometry of blood will be crucial to the discovery and
      analysis of proteins, enzyme activities, and post-translational processes that
      underlay the mechanisms of disease. At present both discovery and quantification
      of proteins from blood are commonly reaching sensitivities of ~1 ng/mL.

PMID- 24737630
TI  - The Rosetta Stone of isotope science and the uranium/lead system.
AB  - The nucleosynthetic characteristics of U and Pb, together with the
      interconnectivity between these elements by two radioactive decay chains, are the
      foundation on which the U/Pb system was able to make a unique contribution to
      isotope science. The Rosetta Stone is an ancient Egyptian tablet that enabled
      previously indecipherable hieroglyphics to be translated. In a similar manner,
      the isotopic investigation of the U/Pb system, by a variety of mass spectrometric
      instrumentation, has led to our knowledge of the age of the Earth and contributed
      to thermochronology. In a similar manner, climate change information has been
      garnered by utilizing the U-Disequilibrium Series to measure the ages of marine
      archives. The impact of Pb in the environment has been demonstrated in human
      health, particularly at the peak of leaded petrol consumption in motor vehicles
      in the 1970s. Variations in the isotopic composition of lead in samples enable
      the source of the lead to be "fingerprinted" so as to trace the history of the Pb
      in ice cores and aerosols. The discovery of nuclear fission of (235)U led to the
      development of nuclear reactors and the isotopic investigation of the Oklo
      natural reactors. The mass spectrometer is the modern Rosetta Stone of isotope
      science, which has enabled the isotopic hieroglyphics of the U/Pb system to be
      investigated to reveal new horizons in our understanding of nature, and to
      address a number of societal and environmental problems.

PMID- 24737631
TI  - Determination of drugs and drug-like compounds in different samples with direct
      analysis in real time mass spectrometry.
AB  - Direct analysis in real time (DART), a relatively new ionization source for mass
      spectrometry, ionizes small-molecule components from different kinds of samples
      without any sample preparation and chromatographic separation. The current paper
      reviews the published data available on the determination of drugs and drug-like
      compounds in different matrices with DART-MS, including identification and
      quantitation issues. Parameters that affect ionization efficiency and mass
      spectra composition are also discussed.

PMID- 24737632
TI  - Current mass spectrometry strategies for the analysis of pesticides and their
      metabolites in food and water matrices.
AB  - Analysis of pesticides and their metabolites in food and water matrices continues
      to be an active research area closely related to food safety and environmental
      issues. This review discusses the most widely applied mass spectrometric (MS)
      approaches to pesticide residues analysis over the last few years. The main
      techniques for sample preparation remain solvent extraction and solid-phase
      extraction. The QuEChERS (Quick, Easy, Cheap, Effective, Rugged, Safe) approach
      is being increasingly used for the development of multi-class pesticide residues
      methods in various sample matrices. MS detectors-triple quadrupole (QqQ), ion
      trap (IT), quadrupole linear ion trap (QqLIT), time-of-flight (TOF), and
      quadrupole time-of-flight (QqTOF)-have been established as powerful analytical
      tools sharing a primary role in the detection/quantification and/or
      identification/confirmation of pesticides and their metabolites. Recent
      developments in analytical instrumentation have enabled coupling of ultra
      performance liquid chromatography (UPLC) and fast gas chromatography (GC) with MS
      detectors, and faster analysis for a greater number of pesticides. The newly
      developed "ambient-ionization" MS techniques (e.g., desorption electrospray
      ionization, DESI, and direct analysis in real time, DART) hyphenated with high
      resolution MS platforms without liquid chromatography separation, and sometimes
      with minimum pre-treatment, have shown potential for pesticide residue screening.
      The recently introduced Orbitrap mass spectrometers can provide high resolving
      power and mass accuracy, to tackle complex analytical problems involved in
      pesticide residue analysis.

PMID- 24737634
TI  - Costs and benefits of an organized fecal immunochemical test-based colorectal
      cancer screening program in the United States.
AB  - BACKGROUND: Despite clear recommendations and evidence linking colorectal cancer
      screening to lower incidence and mortality, > 40% of adults are not up to date
      with screening. Existing domestic and international models of organized cancer
      screening programs have been effective in increasing screening rates.
      Implementing an organized, evidence-based, national screening program may be an
      effective approach to increasing screening rates. METHODS: In the current study,
      the authors estimated the initial investment required and the cost per person
      screened of a nationwide fecal immunochemical test (FIT)-based colorectal cancer
      screening program among adults aged 50 years to 75 years. RESULTS: The initial
      additional investment required was estimated at $277.9 to $318.2 million
      annually, with an estimated 8.7 to 9.4 million individuals screened at a cost of
      $32 to $39 per person screened. The program was estimated to prevent 2900 to 3100
      deaths annually. CONCLUSIONS: The results of the current study indicate that
      implementing a national screening program would make a substantial public health
      impact at a moderate cost per person screened. Results from this analysis may
      provide useful information for understanding the public health benefit of an
      organized screening delivery system and the potential resources required to
      implement a nationwide colorectal cancer screening program, and help guide
      decisions about program planning, design, and implementation.

PMID- 24737635
TI  - Oxygenated metabolites of n-3 polyunsaturated fatty acids as potential oxidative
      stress biomarkers: total synthesis of 8-F3t-IsoP, 10-F4t-NeuroP and [D4]-10-F4t
      NeuroP.
AB  - A wide variety of metabolic products of polyunsaturated fatty acids is of
      paramount importance for improving our medical knowledge in the field of oxidized
      lipids. Two novel metabolites of n-3 polyunsaturated fatty acids, 8-F3t-IsoP and
      10-F4t-NeuroP as well as a deuterated derivative thereof were synthesized based
      on an acetylenic intermediate. An original approach achieved lateral chain
      insertion of 8-F3t-IsoP by a ring-closing alkyne metathesis/semi-reduction
      strategy together with a temporary tether.

PMID- 24737636
TI  - Photocatalysis with chromium-doped TiO2: bulk and surface doping.
AB  - The photocatalytic properties of TiO2 modified by chromium are usually found to
      depend strongly on the preparation method. To clarify this problem, two series of
      chromium-doped titania with a chromium content of up to 1.56 wt % have been
      prepared under hydrothermal conditions: the first series (Cr:TiO2) is intended to
      dope the bulk of TiO2, whereas the second series (Cr/TiO2) is intended to load
      the surface of TiO2 with Cr. The catalytic properties have been compared in the
      photocatalytic oxidation of formic acid. Characterization data provides evidence
      that in the Cr/TiO2 catalysts chromium is located on the surface of TiO2 as
      amorphous CrOOH clusters. In contrast, in the Cr:TiO2 series, chromium is mostly
      dissolved in the titania lattice, although a minor part is still present on the
      surface. Photocatalytic tests show that both series of chromium-doped titania
      demonstrate visible-light-driven photo-oxidation activity. Surface-doped Cr/TiO2
      solids appear to be more efficient photocatalysts than the bulk-doped Cr:TiO2
      counterparts.

PMID- 24737637
TI  - Negative and positive consequences of adolescent cancer 10 years after diagnosis:
      an interview-based longitudinal study in Sweden.
AB  - OBJECTIVE: The aim of this study was to provide insight into survivor-reported
      negative and positive consequences of cancer during adolescence 10 years after
      diagnosis and compare these with consequences reported 3 and 4 years after
      diagnosis. METHODS: Three, 4, and 10 years after diagnosis, survivors of
      adolescent cancer were interviewed about negative and positive consequences due
      to their cancer experience. Manifest content analysis was used to identify
      categories of reported consequences. Categories of consequences 10 years after
      diagnosis were compared with consequences reported 3 and 4 years after diagnosis.
      RESULTS: Seven categories of negative consequences were identified: bodily
      concerns, existential thoughts about loss and life (new at 10 years),
      psychological problems, difficulties interacting with others, health worries
      (new), fertility concerns (new), and frustrations about health care (new); and
      six categories of positive consequences: positive view of life, positive view of
      self, compassion for others (new), close relationships, gained knowledge about
      disease and health care, and financial gains. Consistent with previous time
      points, bodily concerns were reported most often. The majority of survivors (n =
      22) reported both negative and positive consequences of their former disease. Few
      reported only negative (n = 2) or only positive consequences (n = 4).
      CONCLUSIONS: Ten years after diagnosis, most survivors reported both negative and
      positive consequences. New themes, relevant to young adulthood and long-term
      survival, were identified. Health care professionals treating young adult
      survivors may anticipate and address problems regarding physical health,
      fertility, and health care but may also reinforce positive affect by addressing
      survivors' positive views of life, sense of self, and close relationships.

PMID- 24737638
TI  - Longitudinal associations between fish consumption and depression in young
      adults.
AB  - Few studies have examined longitudinal associations between fish consumption and
      depression; none have defined depression using a diagnostic tool. We investigated
      whether fish consumption was associated with fewer new depression episodes in a
      national study of Australian adults. In 2004-2006, 1,386 adults aged 26-36 years
      (38% males) completed a 127-item (9 fish items) food frequency questionnaire.
      Fish intake was examined continuously (times/week) and dichotomously (reference
      group: <2 times/week). During 2009-2011, the lifetime version of the Composite
      International Diagnostic Interview was administered by telephone. New episodes of
      major depression/dysthymic disorder (since baseline) were defined using the
      Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition. During
      follow-up, 160 (18.8%) women and 70 (13.1%) men experienced depression. For
      women, each additional weekly serving of fish consumed at baseline decreased the
      risk of having a new depressive episode by 6% (adjusted relative risk = 0.94, 95%
      confidence interval: 0.87, 1.01). Women who ate fish >=2 times/week at baseline
      had a 25% lower risk of depression during follow-up than those who ate fish <2
      times/week (adjusted relative risk = 0.75, 95% confidence interval: 0.57, 0.99).
      Reverse causation was also suggested but appeared to be restricted to persons
      with recent depression. Fish consumption was not associated with depression in
      men. These findings provide further evidence that fish consumption may be
      beneficial for women's mental health.

PMID- 24737640
TI  - Genetic variants of ACE (Insertion/Deletion) and AGT (M268T) genes in patients
      with diabetes and nephropathy.
AB  - INTRODUCTION: Diabetes mellitus (DM) has been a growing epidemic worldwide and
      poses a major socio-economic challenge. The leading cause of DM death is
      nephropathy due to end-stage renal disease (ESRD). This study aims to identify
      the possible association of I/D variants of the ACE gene and M268T (rs699) of the
      AGT gene of renin-angiotensin-aldosterone system (RAAS). MATERIALS AND METHODS:
      Study subjects include 115 patients with DM, 110 with diabetic nephropathy (DN)
      and 110 controls. Fasting blood samples were collected for biochemical analyses
      and PCR amplification of specific regions of the ACE and AGT genes using primers.
      RESULTS: The distribution of ACE (I/D) II 28.8%, ID 35.6% and DD 35.6% while in
      DN II 24.5%, ID 41% and DD 34.5%. The AGT (M268T) genotypes were distributed in
      DM as TT 30.4%, MT 66.9% and MM 2.6% while in DN subjects TT 56.4%, MT 42.7% and
      MM 0.9%. CONCLUSION: Significant differences were observed in the DD genotype and
      D allele of the ACE gene and the TT genotype and T allele of AGT genes between
      diabetic patients with and without nephropathy. The study may conclude that the D
      allele polymorphism in the ACE gene and the T allele polymorphism in AGT gene may
      be considered as genetic risk factors for the development of nephropathy in
      diabetes.

PMID- 24737639
TI  - The renin-angiotensin-aldosterone system in adolescent offspring born prematurely
      to mothers with preeclampsia.
AB  - HYPOTHESIS/INTRODUCTION: Preeclampsia is associated with alterations in the
      maternal renin-angiotensin-aldosterone system (RAAS), increased blood pressure
      (BP), and cardiovascular risk in the offspring. We hypothesized that preeclampsia
      is associated with alterations in the RAAS in the offspring that persist into
      adolescence. MATERIALS AND METHODS: We compared components of the circulating (n
      = 111) and renal (n = 160) RAAS in adolescents born prematurely with very low
      birth weight (VLBW) of preeclamptic (PreE) and normotensive (NoHTN) pregnancies.
      Multivariable linear regression was used to evaluate potential confounding and
      intermediate variables. Analyses were stratified by sex. RESULTS: Adjusting for
      race and antenatal steroid exposure, male offspring of PreE mothers had higher
      circulating aldosterone than those of NoHTN mothers (adjusted mean difference =
      109; 95% confidence limits: -9, 227 pmol/L). Further adjustment for current BMI
      attenuated this difference (adjusted mean difference: 93; 95% confidence limits: 
      30, 215 pmol/L). CONCLUSION: Among male preterm VLBW infants, maternal
      preeclampsia is associated with increased circulating aldosterone level in
      adolescence, which appears to be mediated in part by higher BMI.

PMID- 24737641
TI  - MicroRNA-155 inhibits angiotensin II-induced vascular smooth muscle cell
      proliferation.
AB  - BACKGROUND: MicroRNA-155 (miR-155) is a multifunctional signal microRNA that
      participates in a variety of cardiovascular diseases and is involved in
      physiological and pathological processes in different cell types. OBJECTIVE: The
      objective of this article is to examine the effect of miR-155 on angiotensin II
      (Ang II)-induced primary mice vascular smooth muscle cell (VSMC) proliferation.
      METHODS: Primary cultured VSMCs from the aorta of C57/BL6 mice were incubated
      with Ang II and miR-155. Cells were counted using CCK-8 and EdU, and flow
      cytometric analysis of cell cycle progression was performed. Angiotensin II 1
      type receptor (AT1R) gene and protein expression were measured by real-time
      polymerase chain reaction and Western blotting. RESULTS: 1) Ang II increased the
      viability of VSMCs in a dose- and time-dependent manner. 2) miR-155 opposed the
      Ang II-induced increase in VSMC viability. 3) miR-155 inhibited Ang II-induced
      proliferation of VSMCs. 4) miR-155 increased the number of VSMCs in the G1 phase
      compared to G2 and M cell cycle phases. 5) miR-155 decreased ATR1 gene and
      protein expression. CONCLUSION: miR-155 downregulation of Ang II-induced VSMC
      viability identifies it as an important regulator of cell proliferation.

PMID- 24737642
TI  - Treatment with aliskiren ameliorates tacrolimus-induced nephrotoxicity in rats.
AB  - INTRODUCTION: Tacrolimus is frequently used as immunosuppressive agent in organ
      transplantation but its clinical use is limited due to its marked nephrotoxicity.
      MATERIALS AND METHODS: Male Wistar albino rats weighing 150-200 g (10-12 weeks
      old) were used. Animals were divided into four groups. Group 1 served as control
      group and received normal saline, group 2 served as toxic group and received 2
      mg/kg tacrolimus i.p., group 3 served as treatment group and received 2 mg/kg
      tacrolimus i.p. followed by 2 mg/kg aliskiren orally and group 4 served as drug
      per se group and received 2 mg/kg aliskiren orally. Tacrolimus-induced
      nephrotoxicity was assessed biochemically and histopathologically. RESULTS:
      Treatment with aliskiren decreased the tacrolimus-induced changes in biochemical
      markers of nephrotoxicity such as blood urea nitrogen and creatinine. Aliskiren
      also attenuated the effects of tacrolimus on oxidative stress parameters such as
      malondialdehyde, reduced glutathione and catalase. Histopathological and
      ultrastructural studies showed that aliskiren attenuated tacrolimus-induced renal
      damage. CONCLUSION: These results suggest that aliskiren has protective effects
      against tacrolimus-induced nephrotoxicity; implying that renin inhibitor may
      counteract nephrotic syndrome associated with immunosuppressant use.

PMID- 24737643
TI  - Probing weak intermolecular interactions by using the invariom approach: a
      comparative study of s-tetrazine.
AB  - A comparative study of chemical bonding peculiarities in 1,2,4,5-tetrazine was
      carried out to test the performance of a recently developed invariom approach
      against a conventional charge density analysis of high-resolution X-ray
      diffraction data and quantum chemical calculations within the plane-wave
      functional theory. The amazing similarity between the intermolecular features
      thus obtained for this van der Waals crystal showed the invariom approximation to
      now emerge as a fast and convenient way towards reliable description of weak
      intermolecular interactions. 

PMID- 24737644
TI  - Photoreceptor topography and spectral sensitivity in the common brushtail possum
      (Trichosurus vulpecula).
AB  - Marsupials are believed to be the only non-primate mammals with both trichromatic
      and dichromatic color vision. The diversity of color vision systems present in
      marsupials remains mostly unexplored. Marsupials occupy a diverse range of
      habitats, which may have led to considerable variation in the presence, density,
      distribution, and spectral sensitivity of retinal photoreceptors. In this study
      we analyzed the distribution of photoreceptors in the common brushtail possum
      (Trichosurus vulpecula). Immunohistochemistry in wholemounts revealed three cone
      subpopulations recognized within two spectrally distinct cone classes. Long
      wavelength sensitive (LWS) single cones were the largest cone subgroup (67-86%),
      and formed a weak horizontal visual streak (peak density 2,106 +/- 435/mm2)
      across the central retina. LWS double cones were strongly concentrated ventrally
      (569 +/- 66/mm2), and created a "negative" visual streak (134 +/- 45/mm2) in the
      central retina. The strong regionalization between LWS cone topographies suggests
      differing visual functions. Short-wavelength sensitive (SWS) cones were present
      in much lower densities (3-10%), mostly located ventrally (179 +/- 101/mm2). A
      minority population of cones (0-2.4%) remained unlabeled by both SWS- and LWS
      specific antibodies, and may represent another cone population.
      Microspectrophotometry of LWS cone and rod visual pigments shows peak spectral
      sensitivities at 544 nm and 500 nm, respectively. Cone to ganglion cell
      convergences remain low and constant across the retina, thereby maintaining good
      visual acuity, but poor contrast sensitivity during photopic vision. Given that
      brushtail possums are so strongly nocturnal, we hypothesize that their acuity is
      set by the scotopic visual system, and have minimized the number of cones
      necessary to serve the ganglion cells for photopic vision.

PMID- 24737645
TI  - TRASER: acute phase vascular and follicular changes.
AB  - BACKGROUND AND OBJECTIVES: A TRASER (Total Reflection Amplification of
      Spontaneous Emission of Radiation) is a novel device that utilizes the energy
      from a flashlamp to induce the spontaneous emission of photons from a fluorescent
      medium. This study was designed to observe clinical and histological changes of
      skin treated with two different fluorescent media selected for their peak
      emissions tuned for vascular and hair follicle targets. STUDY DESIGN/MATERIALS
      AND METHODS: A purpuric clinical response for the vascular target was assessed
      with a TRASER using the fluorescent medium Pyrromethene 556 producing a narrow
      spectrum peaking at 544 nm. Using a 12 mm spot and pulse duration of 1 ms,
      treatment pulses with fluences of 6.0-9.5 J/cm2 were given along the forearm of
      subject with photo type II skin. Follicular structures were targeted with the dye
      cell switched to Sulforhodamine 640 Chloride, producing a narrow peak at 654 nm.
      Using a 12 mm spot, single 20 ms pulses with fluencies from 14.0 to 20.0 J/cm2
      were delivered with 5  degrees C contact cooling to the shaved chest of a subject
      with photo type II skin with brown hair. Clinical observations were photographed
      and assessed by two physicians. A 4 mm punch skin biopsy was taken at
      approximately 60 and 30 minutes respectively for both the vascular and hair
      regions. The paraffin embedded H&E stained vertical sections were analyzed by a
      dermatopathologist. RESULTS: A characteristic threshold purpuric response was
      noted at 7.2 J/cm2 . The histological changes consistently showed intravascular
      thrombosis of the small sub-dermal plexus of capillaries down to larger vessels
      approaching the subcutaneous fat. There were no extravasated red blood cells.
      Clinical hair follicle target changes of perifollicular edema and transient
      erythema, similar to those described with standard hair removal lasers, were
      noted. Histologically these were shown to be limited to the target structures.
      CONCLUSION: This is the first demonstration of clinical and histological acute
      phase changes associated with use of a TRASER with wavelengths optimized for
      vascular and follicular targets. The findings of this observational study support
      the notion that the TRASER can be used as an effective vascular and hair removal
      device.

PMID- 24737646
TI  - Facile synthesis of poly(ionic liquid)-bonded magnetic nanospheres as a high
      performance sorbent for the pretreatment and determination of phenolic compounds
      in water samples.
AB  - Poly(ionic liquid)-bonded magnetic nanospheres were easily synthesized and
      applied to the pretreatment and determination of phenolic compounds in water
      samples, which have detrimental effects on water quality and the health of living
      beings. The high affinity of poly(ionic liquid)s toward the target compounds as
      well as the magnetic behavior of Fe3 O4 were combined in this material to provide
      an efficient and simple magnetic solid-phase extraction approach. The adsorption
      behavior of the poly(ionic liquid)-bonded magnetic nanospheres was examined to
      optimize the synthesis. Different parameters affecting the magnetic solid-phase
      extraction of phenolic compounds were assessed in terms of adsorption and
      recovery. Under the optimal conditions, the proposed method showed excellent
      detection sensitivity with limits of detection in the range of 0.3-0.8 ng/mL and
      precision in the range of 1.2-3.3%. This method was also applied successfully to
      the analysis of real water samples; good spiked recoveries over the range of 82.5
      99.2% were obtained. 

PMID- 24737647
TI  - The application of targeted mass spectrometry-based strategies to the detection
      and localization of post-translational modifications.
AB  - This review describes some of the more interesting and imaginative ways in which
      mass spectrometry has been utilized to study a number of important post
      translational modifications over the past two decades; from circa 1990 to 2013. A
      diverse range of modifications is covered, including citrullination, sulfation,
      hydroxylation and sumoylation. A summary of the biological role of each
      modification described, along with some brief mechanistic detail, is also
      included. Emphasis has been placed on strategies specifically aimed at detecting
      target modifications, as opposed to more serendipitous modification discovery
      approaches, which rely upon straightforward product ion scanning methods. The
      authors have intentionally excluded from this review both phosphorylation and
      glycosylation since these major modifications have been extensively reviewed
      elsewhere.

PMID- 24737648
TI  - The Bim deletion polymorphism clinical profile and its relation with tyrosine
      kinase inhibitor resistance in Chinese patients with non-small cell lung cancer.
AB  - BACKGROUND: Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors
      (TKIs) are widely used for the treatment of patients with advanced non-small cell
      lung cancer (NSCLC) who have EGFR mutations. Recent studies have indicated that
      some patients with positive mutations were refractory to EGFR TKIs if they
      harbored a B-cell chronic lymphocytic leukemia/lymphoma (Bcl-2)-like 11 (Bim)
      deletion polymorphism. The objective of the current work was to retrospectively
      study the Bim deletion polymorphism in Chinese patients with NSCLC and its
      correlation with the efficacy of EGFR TKIs. METHODS: Distribution of the Bim
      polymorphism was detected using polymerase chain reaction analysis and direct
      sequencing of DNA from peripheral neutrophils in samples from 352 patients with
      NSCLC. Of the 352 patients, 166 who received TKI therapy and had an activating
      mutation identified were involved in further analysis. Progression-free survival
      (PFS) was the primary endpoint of the subsequent analyses, and the incidence of
      the Bim polymorphism and its relation to clinical benefit from EGFR TKIs also
      were investigated. RESULTS: In total, 45 of 352 patient samples (12.8%) had the
      Bim deletion polymorphism, which was distributed randomly with regard to various
      clinical characteristics. In patients with EGFR mutations who received treatment
      with TKIs, the median PFS and the median objective response rate were 4.7 months
      and 25%, respectively, for those with the Bim deletion polymorphism versus 11
      months (P = .003) and 66% (P = .001), respectively, for those with wild-type Bim.
      Cox regression analysis identified Bim status (P = .016) and sex (P = .002) as
      independent factors predicting clinical benefit from EGFR TKIs in patients with
      EGFR-mutated NSCLC. CONCLUSIONS: The incidence of the Bim deletion polymorphism
      was approximately 13% in this study, and it was associated with a poor clinical
      response to EGFR TKIs in patients who had NSCLC with EGFR mutations.

PMID- 24737649
TI  - Two-electron carbon dioxide reduction catalyzed by rhenium(I)
      bis(imino)acenaphthene carbonyl complexes.
AB  - Rhenium(I) carbonyl complexes carrying substituted bis(arylimino)acenaphthene
      ligands (BIAN-R) have been tested as potential catalysts for the two-electron
      reduction of carbon dioxide. Cyclic voltammetric studies as well as controlled
      potential electrolysis experiments were performed using CO2-saturated solutions
      of the complexes in acetonitrile and acetonitrile-water mixtures. Faradaic
      efficiencies of more than 30 % have been determined for the electrocatalytic
      production of CO. The effects of ligand substitution patterns and water content
      of the reaction medium on the catalytic performance of the new catalysts are
      discussed.

PMID- 24737656
TI  - Ivabradine is cost-effective in the treatment of chronic heart failure.

PMID- 24737651
TI  - Australian men with cancer practice complementary therapies (CTs) as a coping
      strategy.
AB  - OBJECTIVE: The aim of this study was to explore how and why Australian men with
      cancer practice complementary therapies (CTs) and how their significant others
      (SOs) contribute to the regular uptake of CTs. METHODS: This qualitative study
      employed semi-structured interviews with 26 male cancer patients and 24 SOs.
      Participants were purposefully sampled from a preceding Australian survey
      investigating the use of CTs in men with cancer (94% response rate and 86%
      consent rate for follow-up interview). Interviews were conducted in a
      metropolitan location, and the 43 interview transcripts were analyzed
      thematically. RESULTS: Three core themes were identified: men used CTs as (a)
      problem-focused coping (e.g., diet modification), (b) emotion-focused coping
      (e.g., meditation), and (c) meaning-based coping (e.g., prayer). Practicing CTs
      helped men to cope with physical, emotional, and spiritual concerns, although
      some men spoke of difficulties with practicing meditation to regulate their
      emotions. SOs were supportive of men's coping strategies but were only rarely
      involved in men's emotion-focused coping. CONCLUSIONS: Complementary therapies
      have the potential to facilitate coping with cancer, independent of any
      measurable physiological benefit. Our findings suggest that when clinicians
      engage in conversations about CTs use, they should consider the type of coping
      strategy employed by their patient. Such information may enhance the efficacy of
      some interventions (e.g., meditation) and also provide for an opportunity to
      discuss patients' expectations concerning CTs.

PMID- 24737657
TI  - Heparanase expression in Langerhans cell histiocytosis.
AB  - Heparanase is an endo-beta D-glucuronidase capable of cleaving heparan sulfate
      side chains, yielding heparan sulfate fragments. Heparanase activity has been
      correlated with the metastatic potential of tumor-derived cells, angiogenesis,
      autoimmunity and inflammation. We performed a study of heparanase expression in
      specimens obtained from patients with Langerhans cell histiocytosis (LCH).
      Paraffin embedded slides from 25 patients were studied by immunohistochemistry
      for heparanase. Most patients had positive staining for heparanase (21/25). There
      was no positive association with severity of disease and other clinical
      characteristics. Further studies are required to clarify the role of heparanase
      in the pathogenesis of LCH.

PMID- 24737658
TI  - Size control in production and freeze-drying of poly-epsilon-caprolactone
      nanoparticles.
AB  - This work is focused on the control of poly-epsilon-caprolactone nanoparticle
      characteristics, notably size and size distribution, in both the production and
      preservation (by using freeze-drying) stages. Nanoparticles were obtained by
      employing the solvent displacement method in a confined impinging jets mixer. The
      effect of several operating conditions, namely, initial polymer concentration and
      solvent-to-antisolvent flow rate ratio, and the influence of postprocessing
      conditions, such as final dilution and solvent evaporation, on nanoparticle
      characteristics was investigated. Further addition of antisolvent (water) after
      preparation was demonstrated to be effective in obtaining stable nanoparticles,
      that is, avoiding aggregation that would result in larger particles. On the
      contrary, solvent (acetone) evaporation was shown to have a small effect on the
      final nanoparticle characteristics. Eventually, freeze-drying of the solutions
      containing nanoparticles, after solvent evaporation, was also investigated. To
      ensure maximum nanoparticles stability, lyoprotectants (e.g., sucrose and
      mannitol) and steric stabilizers (e.g., Cremophor EL and Poloxamer 388) had to be
      added to the suspensions. The efficacy of the selected lyoprotectants, in the
      presence (or absence) of steric stabilizers, and in various concentrations, to
      avoid particle aggregation during the freeze-drying process was investigated,
      thus pointing to the optimal formulation.

PMID- 24737659
TI  - Live-cell quantitative imaging of proteome degradation by stimulated Raman
      scattering.
AB  - Protein degradation is a regulatory process essential to cell viability and its
      dysfunction is implicated in many diseases, such as aging and neurodegeneration.
      In this report, stimulated Raman scattering microscopy coupled with metabolic
      labeling with (13)C-phenylalanine is used to visualize protein degradation in
      living cells with subcellular resolution. We choose the ring breathing modes of
      endogenous (12)C-phenylalanine and incorporated (13)C-phenylalanine as protein
      markers for the original and nascent proteomes, respectively, and the decay of
      the former wasquantified through (12)C/((12)C+(13)C) ratio maps. We demonstrate
      time-dependent imaging of proteomic degradation in mammalian cells under steady
      state conditions and various perturbations, including oxidative stress, cell
      differentiation, and huntingtin protein aggregation.

PMID- 24737660
TI  - Determination of phthalic acid esters in Chinese white spirit using dispersive
      liquid-liquid microextraction coupled with sweeping beta-cyclodextrin-modified
      micellar electrokinetic chromatography.
AB  - A simple method that consumes low organic solvent is proposed for the analysis of
      phthalic acid esters in Chinese white spirit using dispersive liquid-liquid
      microextraction coupled with sweeping-micellar electrokinetic chromatography.
      Tetrachloromethane and white-spirit-containing ethanol were used as the
      extraction and dispersing solvents, respectively. The electrophoresis separation
      buffer was composed of 5 mM beta-cyclodextrin, 50 mM sodium dodecyl sulfate and
      25 mM borate buffer (pH 9.2) with 9% acetonitrile, enabling the baseline
      resolution of the analytes within 13 min. Under the optimum conditions,
      satisfactory linearities (5-1000 ng/mL, r >= 0.9909), good reproducibility (RSD
      <= 6.7% for peak area, and RSD <= 2.8% for migration time), low detection limits
      (0.4-0.8 ng/mL) and acceptable recovery rates (89.6-105.7%) were obtained. The
      proposed method was successfully applied to 22 Chinese white spirits, and the
      content of dibutyl phthalate in 55% of the samples exceeded the Specific
      Migration Limit of 0.3 mg/kg established by the domestic and international
      regulations. 

PMID- 24737661
TI  - Intraoperative Fluoroscopic Imaging to Treat Cam Deformities: Correlation With 3
      Dimensional Computed Tomography.
AB  - BACKGROUND: In the diagnosis and surgical treatment of cam-type femoroacetabular
      impingement (FAI), 3-dimensional (3D) imaging is the gold standard for detecting
      femoral head-neck junction malformations preoperatively. Intraoperative
      fluoroscopy is used by many surgeons to evaluate and verify adequate correction
      of the deformity. PURPOSE: (1) To compare radial reformatted computed tomography
      (CT) scans with 6 defined intraoperative fluoroscopic views before surgical
      correction to determine whether fluoroscopy could adequately depict cam
      deformity, and (2) to define the influence of femoral version on the clock-face
      location of the maximum cam deformity on these views. STUDY DESIGN: Cohort study
      (diagnosis); Level of evidence, 2. METHODS: A consecutive series of 50 hips (48
      patients) that underwent arthroscopic treatment for symptomatic FAI by a single
      surgeon were analyzed. Each patient underwent a CT scan and 6 consistent
      intraoperative fluoroscopy views: 3 views in hip extension and 3 views in hip
      flexion of 50 degrees . The alpha angles of each of the fluoroscopic images were
      compared with the radial reformatted CT using a 3D software program. Femoral
      version was also defined on CT studies. Statistical analysis was performed using
      the Student t test, with P < .05 defined as significant. RESULTS: Fifty-two
      percent of patients were male, average age 28 years (range, 15-56 years). The
      maximum mean alpha angle on fluoroscopy was 65 degrees  (range, 37 degrees -93
      degrees ) and was located on the anteroposterior (AP) 30 degrees  external
      rotation (ER) fluoroscopy view. In comparison, the mean CT-derived maximum alpha
      angle was 67 degrees  and was located at 1:15 (P = .57). The mean clock-face
      positions of each of the fluoroscopy views (standardized to the right hip) were
      AP 30 degrees  internal rotation, 11:45; AP 0 degrees  (neutral) rotation, 12:30;
      AP 30 degrees  ER, 1:00; flexion/0 degrees  (neutral) rotation, 1:45; flexion/40
      degrees  ER, 2:15; and flexion/60 degrees  ER, 2:45. Increased femoral
      anteversion (>20 degrees ) was associated with a significant change in the
      location of the maximum alpha angle (1:45 vs 1:15; P = .002). CONCLUSION: The
      described 6 fluoroscopic views are very helpful in localization and visualization
      of the typical cam deformity from 11:45 to 2:45 and can be used to reliably
      confirm a complete intraoperative resection of cam-type deformity in most
      patients. These views correlate with preoperative 3D imaging and may be of even
      greater importance in the absence of preoperative 3D imaging.

PMID- 24737662
TI  - Numerical Magnitude Representation in Children With Mathematical Difficulties
      With or Without Reading Difficulties.
AB  - This study aimed to explore the spatial numerical association of response codes
      (SNARC), the flanker, and the numerical distance effects in children with
      mathematical difficulties. From a sample of 720 third, fourth, and fifth graders,
      60 children were selected and divided into the following three groups: typically
      developing children (TD; n = 29), children with mathematical difficulties only
      (MD only; n = 21), and children with mathematical and reading difficulties
      (MD+RD; n = 10). Children were tested with a numerical Eriksen task that was
      built to assess SNARC, numerical distance, and flanker (first and second order
      congruency) effects. Children with MD only showed stronger SNARC and second order
      congruency effects than did TD children, whereas the numerical distance effects
      were similar across the three groups. Finally, the first order congruency effect
      was associated with reading difficulties. These results showed that children with
      mathematical difficulties with or without reading difficulties were globally more
      impaired when spatial incompatibilities were presented. 

PMID- 24737663
TI  - A compact tetrathiafulvalene-benzothiadiazole dyad and its highly symmetrical
      charge-transfer salt: ordered donor pi-stacks closely bound to their acceptors.
AB  - A compact and planar donor-acceptor molecule 1 comprising tetrathiafulvalene
      (TTF) and benzothiadiazole (BTD) units has been synthesised and experimentally
      characterised by structural, optical, and electrochemical methods. Solution
      processed and thermally evaporated thin films of 1 have also been explored as
      active materials in organic field-effect transistors (OFETs). For these devices,
      hole field-effect mobilities of MUFE = (1.3+/-0.5)*10(-3) and (2.7+/-0.4)*10(-3) 
      cm(2)  V s(-1) were determined for the solution-processed and thermally
      evaporated thin films, respectively. An intense intramolecular charge-transfer
      (ICT) transition at around 495 nm dominates the optical absorption spectrum of
      the neutral dyad, which also shows a weak emission from its ICT state. The iodine
      induced oxidation of 1 leads to a partially oxidised crystalline charge-transfer
      (CT) salt {(1)2I3}, and eventually also to a fully oxidised compound {1I3}?1/2I2.
      Single crystals of the former CT compound, exhibiting a highly symmetrical
      crystal structure, reveal a fairly good room temperature electrical conductivity
      of the order of 2 S cm(-1). The one-dimensional spin system bears compactly
      bonded BTD acceptors (spatial localisation of the LUMO) along its ridge.

PMID- 24737664
TI  - BRAF mutation predicts for poor outcomes after metastasectomy in patients with
      metastatic colorectal cancer.
AB  - BACKGROUND: BRAF mutations occur in 5% to 11% of patients with metastatic
      colorectal cancer (mCRC) and have been associated with poor prognosis. The
      current study was undertaken to determine the clinicopathologic characteristics,
      PIK3CA (phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha)
      mutation frequency, and outcomes after metastasectomy in patients with BRAF
      mutant mCRC. METHODS: Data from 1941 consecutive patients with mCRC who underwent
      KRAS/BRAF mutation testing between 2009 and 2012 at a single institution were
      identified to identify BRAF-mutant mCRC cases (92 cases). BRAF wild-type mCRC
      cases from 2011 (423 cases) served as a control group. RESULTS: BRAF-mutated mCRC
      was found to be significantly associated with older age at diagnosis, female sex,
      right-sided location, poorly differentiated morphology, and mucinous histology
      compared with wild-type cases. BRAF-mutant cases more frequently progressed from
      stage III disease (32% vs 17%; P = .003) and among those patients with stage III
      disease, T4 disease was more common (48% vs 27%; P = .05). PIK3CA was found to be
      co-mutated in 5% of BRAF-mutant tumors versus 17% of KRAS-mutant tumors (P < .01)
      and 4% of BRAF/KRAS wild-type cases. Patients with BRAF-mutated mCRC presented
      more frequently with peritoneal involvement (26% vs 14%; P < 0.01) and less
      frequently with liver-limited metastases (41% vs 63%; P < .01). Patients with
      BRAF-mutated mCRC were less likely to undergo metastasectomy (41% vs 26% at 2
      years from diagnosis of metastatic disease; P < .01) and were found to have lower
      overall survival (P < .01) after metastasectomy. CONCLUSIONS: BRAF-mutant mCRC is
      associated with worse clinical outcome. Patients with BRAF-mutant tumors more
      commonly develop peritoneal metastases, less frequently present with disease
      limited to the liver, and have shorter survival after metastasectomy compared
      with patients with BRAF wild-type tumors.

PMID- 24737665
TI  - Chemically stable perovskites as cathode materials for solid oxide fuel cells: La
      doped Ba0.5Sr0.5Co0.8Fe0.2O(3-delta).
AB  - Ba0.5Sr0.5Co0.8Fe0.2O(3-delta) (BSCF) has won tremendous attention as a cathode
      material for intermediate-temperature solid-oxide fuel cells (IT-SOFC) on the
      basis of its fast oxygen-ion transport properties. Nevertheless, wide application
      of BSCF is impeded by its phase instabilities at intermediate temperature. Here
      we report on a chemically stable SOFC cathode material,
      La0.5Ba0.25Sr0.25Co0.8Fe0.2O(3-delta) (LBSCF), prepared by strategic approaches
      using the Goldschmidt tolerance factor. The tolerance factors of LBSCF and BSCF
      indicate that the structure of the former has a smaller deformation of cubic
      symmetry than that of the latter. The electrical property and electrochemical
      performance of LBSCF are improved compared with those of BSCF. LBSCF also shows
      excellent chemical stability under air, a CO2-containg atmosphere, and low oxygen
      partial pressure while BSCF decomposed under the same conditions. Together with
      this excellent stability, LBSCF shows a power density of 0.81 W cm(-2) after 100
      h, whereas 25 % degradation for BSCF is observed after 100 h.

PMID- 24737666
TI  - Altered vimentin protein expression in human dermal microvascular endothelial
      cells after ultraviolet or intense pulsed light treatment.
AB  - BACKGROUND: Endothelial cell senescence is closely related to tissue aging and
      age-related vascular disease. Detailed pathophysiology and essential biomarkers
      of skin aging are not well known. A recent report suggests that advanced
      glycosylation end products, especially N(epsilon) -(carboxymethyl)lysine (CML)
      modification of vimentin, accelerate the aging process. OBJECTIVES: To identify
      protein biomarkers of aging in skin. MATERIALS AND METHODS: Proteomics analysis
      was performed to identify differentially expressed proteins in human dermal
      microvascular endothelial cells (HDMEC) treated with ultraviolet (UV) or intense
      pulsed light (IPL). Proteome maps of UV-treated, IPL-treated, and untreated HDMEC
      were constructed, with identification of altered protein spots by matrix-assisted
      laser desorption/ionization mass spectrometry. Differential expression and
      glycation modification of vimentin were found by this approach and further
      examined by fluorescence-activated cell sorting. RESULTS: Twenty-two
      differentially expressed protein spots were identified. Among them, vimentin was
      specifically up-regulated in UV-treated HDMECs. On the other hand, it was down
      regulated after IPL. Increased expression of CML-vimentin in HDMEC during culture
      (Passage 6 vs. 12) was noted, and this effect was reversed by IPL treatment.
      CONCLUSION: Vimentin and CML should be useful markers for cell senescence, as
      well as for evaluating the level of aging. Also, targeting increased vimentin
      expression and its advanced glycation end products could present a target for the
      treatment of skin aging.

PMID- 24737667
TI  - Rejoinder.
AB  - This is the reply to the discussion of the two companion articles on the theory
      and application of "probability estimation with machine learning methods for
      dichotomous and multicategory outcome" by Kruppa et al. (2014; 534-563 and 564
      583). The five discussion papers are Binder (2014; 584-587), Boulesteix and
      Schmid (2014; 588-593), Shin and Wu (2014; 594-596), Simon (2014; 597-600), and
      Steyerberg et al. (2014; 601-606). 

PMID- 24737670
TI  - Separation and determination of homogenous fatty alcohol ethoxylates by liquid
      chromatography with mulitstage mass spectrometry.
AB  - Alcohol ethoxylates (AEs) are a significant component of a stream of surfactants
      directed to the aquatic environment. The aim of this work was the investigation
      of the dependence of the analytical signals of homogeneous AE homologues on
      liquid chromatography with tandem mass spectrometry conditions, as well as the
      separation of AEs from the water matrix and, on this basis, the development of an
      analytical procedure suitable for the determination of AEs in environmental
      samples. Homogeneous homologues containing dodecyl moiety and 2-9 oxyethylene
      subunits were investigated. The analytical signals of the investigated homologues
      were optimized in terms of concentration of ammonium acetate in the mobile phase
      (optimum 5 mM) and a column temperature (optimum 35 degrees C) of the liquid
      chromatography with tandem mass spectrometry system. A separation of AEs from the
      water matrix by liquid-liquid extraction (ethyl acetate, chloroform) or solid
      phase extraction (C18 , styrene divinylbenzene, H-RX) was investigated. In a
      model investigation, the best recoveries (>90%) were obtained with a styrene
      divinylbenzene cartridge eluted with a 1:1 mixture of chloroform and methanol.
      However, much worse recoveries were obtained from the river water sample. Better
      results were obtained for liquid-liquid extraction with ethyl acetate. Recoveries
      of 62-80% were obtained for homologues having 4-9 oxyethylene subunits, at the
      lowest spike. 

PMID- 24737669
TI  - Testing the differential effects of symptom management interventions in cancer.
AB  - OBJECTIVE: The purpose of this study was to test for moderating effects of
      patient characteristics on self-management interventions developed to address
      symptoms during cancer treatment. Patient's age, education, and depressive
      symptomatology were considered as potential moderators. METHODS: A secondary
      analysis of data of 782 patients from two randomized clinical trials was
      performed. Both trials enrolled patients with solid tumors undergoing
      chemotherapy. After completing baseline interviews, patients were randomized to a
      nurse-delivered intervention versus intervention delivered by a 'coach' in trial
      I and to a nurse-delivered intervention versus an intervention delivered by an
      automated voice response system in trial II. In each of the two trials, following
      a six-contact 8-week intervention, patients were interviewed at week 10 to assess
      the primary outcome of symptom severity. RESULTS: Although nurse-delivered
      intervention proved no better than the coach or automated system in lowering
      symptom severity, important differences in the intervention by age were found in
      both trials. Patients aged <=45 years responded better to the coach or automated
      system, whereas those aged >=75 years favored the nurse. Education and depressive
      symptomatology did not modify the intervention effects in either of the two
      trials. Depressive symptomatology had a significant main effect on symptom
      severity at week 10 in both trials (p = 0.03 and p < 0.01, respectively).
      Education was not associated with symptom severity over and above age and
      depressive symptomatology. CONCLUSIONS: Clinicians need to carefully consider the
      age of the population when using or testing interventions to manage symptoms
      among cancer patients.

PMID- 24737671
TI  - ACTIN-RELATED PROTEIN6 Regulates Female Meiosis by Modulating Meiotic Gene
      Expression in Arabidopsis.
AB  - In flowering plants, meiocytes develop from subepidermal cells in anthers and
      ovules. The mechanisms that integrate gene-regulatory processes with meiotic
      programs during reproductive development remain poorly characterized. Here, we
      show that Arabidopsis thaliana plants deficient in ACTIN-RELATED PROTEIN6 (ARP6),
      a subunit of the SWR1 ATP-dependent chromatin-remodeling complex, exhibit defects
      in prophase I of female meiosis. We found that this meiotic defect is likely due
      to dysregulated expression of meiotic genes, particularly those involved in
      meiotic recombination, including DMC1 (DISRUPTED MEIOTIC cDNA1). Analysis of DMC1
      expression in arp6 mutant plants indicated that ARP6 inhibits expression of DMC1
      in the megasporocyte and surrounding nonsporogeneous ovule cells before meiosis.
      After cells enter meiosis, however, ARP6 activates DMC1 expression specifically
      in the megasporocyte even as it continues to inhibit DMC1 expression in the
      nonsporogenous ovule cells. We further show that deposition of the histone
      variant H2A.Z, mediated by the SWR1 chromatin-remodeling complex at the DMC1 gene
      body, requires ARP6. Therefore, ARP6 regulates female meiosis by determining the
      spatial and temporal patterns of gene expression required for proper meiosis
      during ovule development.

PMID- 24737672
TI  - Arabidopsis Class I alpha-Mannosidases MNS4 and MNS5 Are Involved in Endoplasmic
      Reticulum-Associated Degradation of Misfolded Glycoproteins.
AB  - To ensure that aberrantly folded proteins are cleared from the endoplasmic
      reticulum (ER), all eukaryotic cells possess a mechanism known as endoplasmic
      reticulum-associated degradation (ERAD). Many secretory proteins are N
      glycosylated, and despite some recent progress, little is known about the
      mechanism that selects misfolded glycoproteins for degradation in plants. Here,
      we investigated the role of Arabidopsis thaliana class I alpha-mannosidases (MNS1
      to MNS5) in glycan-dependent ERAD. Our genetic and biochemical data show that the
      two ER-resident proteins MNS4 and MNS5 are involved in the degradation of
      misfolded variants of the heavily glycosylated brassinosteroid receptor,
      BRASSINOSTEROID INSENSITIVE1, while MNS1 to MNS3 appear dispensable for this ERAD
      process. By contrast, N-glycan analysis of different mns mutant combinations
      revealed that MNS4 and MNS5 are not involved in regular N-glycan processing of
      properly folded secretory glycoproteins. Overexpression of MNS4 or MNS5 together
      with ER-retained glycoproteins indicates further that both enzymes can convert
      Glc0-1Man8-9GlcNAc2 into N-glycans with a terminal alpha1,6-linked Man residue in
      the C-branch. Thus, MNS4 and MNS5 function in the formation of unique N-glycan
      structures that are specifically recognized by other components of the ERAD
      machinery, which ultimately results in the disposal of misfolded glycoproteins.

PMID- 24737674
TI  - The role of fore- and hindlimbs during jumping in the Dybowski's frog (Rana
      dybowskii).
AB  - Anurans are well known for their jumping abilities, making use of their strong
      hindlimbs. In contrast, the function of the forelimbs during take-off has rarely
      been studied. We measured the ground reaction forces exerted by forelimbs and
      hindlimbs during short jumps in the Dybowski's frog Rana dybowskii. Take-off
      occurred in two phases. Phase one (from the initial time until the forelimbs took
      off), which lasts a relatively long time (63.2 +/- 4.1% of the total take-off
      phase, N = 20), provides sufficient time for the forelimbs to elevate the body to
      a suitable posture to deliver the best take-off angle. Phase two (from the
      forelimbs lift-off until hindlimbs lift-off) was dominated by the hindlimbs which
      provided a constant and fast elevation. The force angle (angle of the resultant
      vector from fore-aft and normal force components towards the plane of the
      substrate) of the hindlimbs and body trajectory was variable before the forelimbs
      lifted off of the substrate and then primarily followed the direction of the line
      from the foot-substrate point to the center of mass (COM). The preparation angle
      adopted when the forelimbs lifted off of the substrate was a good predictor of
      the take-off angle. The total normal force oscillated around body weight (BW)
      before the forelimb normal force peaked. The BW shifted from the hindlimbs to the
      forelimbs during the initial phase of take-off. A simple lever model suggests
      that the forelimbs are responsible for raising the COM, thus influencing the take
      off angle in short jumps.

PMID- 24737673
TI  - Homoeologous Chromosome Sorting and Progression of Meiotic Recombination in
      Brassica napus: Ploidy Does Matter!
AB  - Meiotic recombination is the fundamental process that produces balanced gametes
      and generates diversity within species. For successful meiosis, crossovers must
      form between homologous chromosomes. This condition is more difficult to fulfill
      in allopolyploid species, which have more than two sets of related chromosomes
      (homoeologs). Here, we investigated the formation, progression, and completion of
      several key hallmarks of meiosis in Brassica napus (AACC), a young polyphyletic
      allotetraploid crop species with closely related homoeologous chromosomes.
      Altogether, our results demonstrate a precocious and efficient sorting of
      homologous versus homoeologous chromosomes during early prophase I in two
      representative B. napus accessions that otherwise show a genotypic difference in
      the progression of homologous recombination. More strikingly, our detailed
      comparison of meiosis in near isogenic allohaploid and euploid plants showed that
      the mechanism(s) promoting efficient chromosome sorting in euploids is adjusted
      to promote crossover formation between homoeologs in allohaploids. This suggests
      that, in contrast to other polyploid species, chromosome sorting is context
      dependent in B. napus.

PMID- 24737675
TI  - Asymmetric synthesis of spiropyrazolones through phosphine-catalyzed [4+1]
      annulation.
AB  - An enantioselective synthesis of spiropyrazolones from allenoate-derived MBH
      acetates and pyrazolones through a phosphine-mediated [4+1] annulation process
      has been developed. Spiropyrazolones were readily prepared in good chemical
      yields and good to high enantioselectivities. This is the first asymmetric
      example in which alpha-substituted allenoates were utilized as a C4 synthon for
      phosphine-catalyzed [4+1] annulation. 

PMID- 24737677
TI  - Is microsatellite instability a prognostic marker in gastric cancer? A systematic
      review with meta-analysis.
AB  - BACKGROUND AND OBJECTIVE: The relationship between survival in gastric cancer
      patients and the status of microsatellite instability (MSI) has not yet been
      established. The purpose of this meta-analysis was to obtain integrated and more
      precise data for the value of MSI as a prognostic marker in gastric cancer.
      METHODS: A comprehensive systematic review and meta-analysis were conducted using
      major electronic databases (PubMed, EMBASE, and the Cochrane Central) with
      keywords related to "microsatellite instability," "gastric cancer," and
      "prognosis." RESULTS: Twenty-four studies with 5,438 participants (712 cases were
      MSI gastric cancer) were included for pooling risk estimates of MSI in gastric
      cancer. Seventeen studies reported overall survival. The pooled hazard ratio (HR)
      for overall survival of MSI vs. non-MSI was 0.72 (95%CI: 0.59-0.88, P = .001) in
      a random-effects model. In the sensitivity analysis, the result from the most
      recent study showed the most heterogeneity. CONCLUSION: MSI gastric cancer was
      associated with good prognosis but there was heterogeneity in the recent studies.
      Changed epidemiology and effects of chemotherapy are potential causes of
      heterogeneity. Establishing a consensus for defining MSI in gastric cancer should
      be preferred for future studies.

PMID- 24737678
TI  - TPMT and MTHFR genotype is not associated with altered risk of thioguanine
      related sinusoidal obstruction syndrome in pediatric acute lymphoblastic
      leukemia: a report from the Children's Oncology Group.
AB  - Sinusoidal obstruction syndrome is a complication of therapy for pediatric ALL
      and may be modified by thiopurine methyltransferase activity as well as by MTHFR
      genotype. We assessed TPMT *3A, *3B, *3C, and MTHFR C677T and A1298C germline
      genetic polymorphisms among 351 patients enrolled in the thioguanine treatment
      arm of CCG-1952 clinical trial. TPMT and MTHFR C677T genotypes were not
      associated with SOS risk. The combination of MTHFR and TPMT variant genotypes was
      not associated with SOS risk. These suggest that germline genetic variation in
      TPMT and MTHFR do not significantly alter SOS risk in patients exposed to
      thioguanine.

PMID- 24737679
TI  - Nuclear receptor nur77 promotes cerebral cell apoptosis and induces early brain
      injury after experimental subarachnoid hemorrhage in rats.
AB  - Nur77 is a potent proapoptotic member of the nuclear receptor superfamily that is
      expressed predominantly in brain tissue. It has been demonstrated that Nur77
      mediates apoptosis in multiple organs. Nur77-mediated early brain injury (EBI)
      involves a conformational change in BCL-2 and triggers cytochrome C (cytoC)
      release resulting in cellular apoptosis. This study investigates whether Nur77
      can promote cerebral cell apoptosis after experimentally induced subarachnoid
      hemorrhage (SAH) in rats. Sprague Dawley rats were randomly assigned to three
      groups: 1) untreated group, 2) treatment control group, and 3) SAH group. The
      experimental SAH group was divided into four subgroups, corresponding to 12 hr,
      24 hr, 48 hr, and 72 hr after experimentally induced SAH. It remains unclear
      whether Nur77 can play an important role during EBI after SAH as a proapoptotic
      protein in cerebral cells. Cytosporone B (Csn-B) was used to demonstrate that
      Nur77 could be enriched and used to aggravate EBI after SAH. Rats treated with
      Csn-B were given an intraperitoneal injection (13 mg/kg) 30 min after
      experimentally induced SAH. We found that Nur77 promotes cerebral cell apoptosis
      by mediating EBI and triggering a conformational change in BCL-2, resulting in
      cytoC release. Nur77 activity, along with cerebral cell apoptosis, peaked at 24
      hr after SAH onset. After induction of SAH, an injection of Csn-B, an agonist for
      Nur77, enhanced the expression and function of Nur77. In summary, we have
      demonstrated the proapoptotic effect of Nur77 within cerebral cells, an effect
      that can be further exacerbated with Csn-B stimulation.

PMID- 24737681
TI  - Nasogastric tube placement and verification in children: review of the current
      literature.
AB  - Placement of a nasogastric enteral access device (NG-EAD), often referred to as a
      nasogastric tube, is a common practice and largely in the domain of nursing care.
      Most often an NG-EAD is placed at the bedside without radiographic assistance.
      Correct initial placement and ongoing location verification are the primary
      challenges surrounding NG-EAD use and have implications for patient safety.
      Although considered an innocuous procedure, placement of an NG-EAD carries risk
      of serious and potentially lethal complications. Despite acknowledgment that an
      abdominal radiograph is the gold standard, other methods of verifying placement
      location are widely used and have success rates from 80% to 85%. The long
      standing challenges surrounding bedside placement of NG-EADs and a practice alert
      issued by the Child Health Patient Safety Organization on this issue were the
      stimuli for the conception of The New Opportunities for Verification of Enteral
      Tube Location Project sponsored by the American Society for Parenteral and
      Enteral Nutrition. Its mission is to identify and promote best practices with the
      potential of technology development that will enable accurate determination of NG
      EAD placement for both the inpatient and outpatient pediatric populations. This
      article presents the challenges of bedside NG-EAD placement and ongoing location
      verification in children through an overview of the current state of the science.
      It is important for all healthcare professionals to be knowledgeable about the
      current literature, to be vigilant for possible complications, and to avoid
      complacency with NG-EAD placement and ongoing verification of tube location. 

PMID- 24737683
TI  - Simultaneous determination of trifloxystrobin and trifloxystrobin acid residue in
      rice and soil by a modified quick, easy, cheap, effective, rugged, and safe
      method using ultra high performance liquid chromatography with tandem mass
      spectrometry.
AB  - A sensitive analytical method for the simultaneous determination of
      trifloxystrobin and its metabolite trifloxystrobin acid in rice including straw,
      bran, brown rice and soil was developed by using ultra high performance liquid
      chromatography coupled with tandem mass spectrometry. The fungicide
      trifloxystrobin and its metabolite trifloxystrobin acid were extracted using
      acetonitrile with 1% formic acid v/v and subsequently cleaned up by primary
      secondary amine, octadecylsilane or graphitized carbon black prior to ultra high
      performance liquid chromatography coupled with tandem mass spectrometry. The
      determination of two target compounds was achieved in less than 3 min using an
      electrospray ionization source in positive mode. The limits of detection were
      below 0.22 MUg/kg and the limits of quantification did not exceed 0.74 MUg/kg in
      all matrices, which were much lower than the maximum residue levels established
      by the Codex Alimentarius Commission. The overall average recoveries in four
      matrix at three levels (0.1, 1.0 and 5.0 mg/kg) ranged from 74.2 to 107.4% with a
      relative standard deviations of less than 7.8% (n = 5) for both analytes. The
      method was demonstrated to be convenient and reliable for the routine monitoring
      of trifloxystrobin and its metabolite. The developed method was validated and
      applied for the analysis of degradation study samples. 

PMID- 24737682
TI  - Hearing evaluation of patients with head and neck cancer: Comparison of Common
      Terminology Criteria for Adverse Events, Brock and Chang adverse event criteria
      in patients receiving cisplatin.
AB  - BACKGROUND: The purpose of this study was to compare Common Terminology Criteria
      for Adverse Events (CTCAE), Brock and Chang hearing loss grading in patients with
      head and neck cancer receiving cis-diamminedichloroplatinum (CDDP). Endpoints
      were baseline distribution of hearing loss, interobserver consistency, and
      sensitivity to hearing loss after CDDP treatment. METHODS: Four hundred sixty
      single ear audiograms in 110 patients with head and neck cancer were graded.
      Hearing loss at baseline, interobserver agreement rates, and changes in hearing
      loss after CDDP were evaluated. RESULTS: The Chang and Brock tools' baseline
      hearing loss distribution was concentrated at grade 0 (57% and 41%,
      respectively), whereas 47%, per the CTCAE, had grade 3 baseline hearing loss.
      Interobserver agreement was highest for the Brock scale (>=90%) followed by the
      Chang (>=89%) and CTCAE (>=75%) scales. Detection of change after CDDP was
      highest for Chang (48%) followed by Brock (45%) and the CTCAE (32%). CONCLUSION:
      The Brock and Chang tools may be superior to the CTCAE in patients with head and
      neck cancer receiving CDDP using baseline hearing loss distribution,
      interobserver agreement, and detection of hearing loss grade change as
      performance indicators.

PMID- 24737685
TI  - Improved long-term survival after resection of colorectal liver metastases
      following staging with FDG positron emission tomography.
AB  - BACKGROUND AND OBJECTIVES: Actual long-term survival of patients with colorectal
      liver metastases staged by PET CT has not been reported. Objectives were to
      investigate whether PET CT staging results in actual improved long-term survival,
      to examine outcome in patients with 'equivocal' PET CT scans, and those excluded
      from hepatectomy by PET CT. METHODS: A retrospective analysis of patients
      undergoing hepatectomy for colorectal liver metastases between March 1998 and
      September 2008. RESULTS: Overall 5- and 10-year survival was 44.8% and 23.9%. PET
      CT staging resulted in management changes in 23% of patients. PET CT staged
      patients showed significantly better survival than those staged by CT alone at 3
      years (79.8% vs. 54.1%) and at 5 years (54.1% vs. 37.3%) with median survivals of
      6.4 years versus 3.9 years (log rank P = 0.018). Patients with equivocal PET CT
      scans showed worse median survival than those with favourable PET CT (log rank P
      = 0.002), but may include a subpopulation whose prognosis trends towards a more
      favourable outcome than those excluded from liver resection by PET CT, whose
      median survival remains limited to 21 months. CONCLUSIONS: Staging of patients
      with colorectal liver metastases by PET CT is associated with significantly
      improved actual long-term survival, and provides valuable prognostic information
      which guides surgical and oncological treatments.

PMID- 24737684
TI  - Facial nerve regeneration using basic fibroblast growth factor-impregnated
      gelatin microspheres in a rat model.
AB  - Basic fibroblast growth factor (bFGF) plays a crucial role in the regeneration of
      peripheral nerve defects by affecting nerve cells, Schwann cells and fibroblasts,
      and by promoting axon outgrowth from the proximal nerve stump. However, the use
      of exogenous bFGF for in vivo regeneration of the peripheral nerves is limited by
      its short in vivo half-life. In this study, a drug delivery system for bFGF was
      developed that uses acidic gelatin hydrogel, which sustainably released bFGF in
      vivo over several weeks; its ability to promote peripheral nerve regeneration was
      also examined. In 8-week-old Lewis rats, 7-mm gaps were made in the buccal branch
      of the left facial nerve. Acidic gelatin hydrogel microspheres (10 ul) with or
      without bFGF (50 ug) were infused into a 10 mm silicone tube using a
      micropipette, and the silicone tube was then implanted into the gap. A 1-mm long
      nerve stump was inserted into each end of the tube. Histological examination at 7
      weeks after implantation revealed (1) a significantly increased rate of nerve
      regeneration, (2) inducement of a number of regenerating nerve axons, and (3) a
      better degree of maturation of nerve axons in the bFGF microsphere group than
      that in the bFGF-free microsphere group. Copyright (c) 2014 John Wiley & Sons,
      Ltd.

PMID- 24737686
TI  - Ureidopeptide-based Bronsted bases: design, synthesis and application to the
      catalytic enantioselective synthesis of beta-amino nitriles from
      (arylsulfonyl)acetonitriles.
AB  - The addition of cyanoalkyl moieties to imines is a very attractive method for the
      preparation of beta-amino nitriles. We present a highly efficient organocatalytic
      methodology for the stereoselective synthesis of beta-amino nitriles, in which
      the key to success is the use of ureidopeptide-based Bronsted base catalysts in
      combination with (arylsulfonyl)acetonitriles as synthetic equivalents of the
      acetonitrile anion. The method gives access to a variety of beta-amino nitriles
      with good yields and excellent enantioselectivities, and broadens the
      stereoselective Mannich-type methodologies available for their synthesis. 

PMID- 24737687
TI  - Fluorescent mimetics of CMP-Neu5Ac are highly potent, cell-permeable polarization
      probes of eukaryotic and bacterial sialyltransferases and inhibit cellular
      sialylation.
AB  - Oligosaccharides of the glycolipids and glycoproteins at the outer membranes of
      human cells carry terminal neuraminic acids, which are responsible for
      recognition events and adhesion of cells, bacteria, and virus particles. The
      synthesis of neuraminic acid containing glycosides is accomplished by
      intracellular sialyl transferases. Therefore, the chemical manipulation of
      cellular sialylation could be very important to interfere with cancer
      development, inflammations, and infections. The development and applications of
      the first nanomolar fluorescent inhibitors of sialyl transferases are described
      herein. The obtained carbohydrate-nucleotide mimetics were found to bind all four
      commercially available and tested eukaryotic and bacterial sialyl transferases in
      a fluorescence polarization assay. Moreover, it was observed that the anionic
      mimetics intruded rapidly and efficiently into cells in vesicles and translocated
      to cellular organelles surrounding the nucleus of CHO cells. The new compounds
      inhibit cellular sialylation in two cell lines and open new perspectives for
      investigations of cellular sialylation. 

PMID- 24737688
TI  - The safety and efficacy of 12 versus 24 hours of tirofiban infusion in patients
      undergoing primary percutaneous coronary intervention.
AB  - AIM: We aimed to investigate the 6-month efficacy and safety of postprocedural 12
      hour tirofiban administration versus 24-hour tirofiban administration in patients
      with ST-segment elevated myocardial infarction (STEMI) who underwent primary
      percutaneous coronary intervention (PCI). METHODS: This retrospective study
      enrolled 349 patients with STEMI who underwent primary PCI. Following the
      administration of bolus tirofiban after primary PCI, those receiving a 12-hour
      tirofiban infusion as the maintenance dose were classified as group 1 (n = 123)
      while those receiving a 24-hour infusion were classified as group 2 (n = 226). In
      hospital and 6-month major adverse cardiac events were recorded. RESULTS: There
      were no statistically significant differences between the 2 groups regarding in
      hospital efficacy (in-hospital death: 4.4% vs 5.7%, P = .600 and stent thrombosis
      1.8% vs 1.6%, P = .921) and in-hospital safety (2.6% vs 1.6% for major bleeding
      and 5.3% vs 4.1% for minor bleeding, P = .562). During the 6-month follow-up
      period, the incidence of the recurrent revascularization (16.1% vs 15.5%, odds
      ratio [OR] = 1.05 [0.47-3.67]), the repeated nonfatal acute coronary syndrome
      and/or stent thrombosis (27% vs 24.4%, P = .598, OR = 1.02 [0.42-2.48]), and the
      cardiovascular deaths (6.6% vs 6.5%, P = .943, OR = 1.03 [0.43-2.43]) were
      comparable between group 1 and group 2. CONCLUSION: Our study revealed that 12
      hour tirofiban administration versus 24-hour tirofiban administration in STEMI
      who underwent primary PCI was similar with respect to in-hospital efficacy and
      safety and major adverse cardiac events during 6-month follow-up.

PMID- 24737689
TI  - Aqueous self-assembly and cation selectivity of cobaltabisdicarbollide dianionic
      dumbbells.
AB  - The anion [3,3'-Co(C2B9H11)2](-) ([COSAN](-)) produces aggregates in water. These
      aggregates are interpreted to be the result of C-H???H-B interactions. It is
      possible to generate aggregates even after the incorporation of additional
      functional groups into the [COSAN](-) units. The approach is to join two [COSAN](
      ) anions by a linker that can adapt itself to act as a crown ether. The linker
      has been chosen to have six oxygen atoms, which is the ideal number for K(+)
      selectivity in crown ethers. The linker binds the alkaline metal ions with
      different affinities; thus showing a distinct degree of selectivity. The highest
      affinity is shown towards K(+) from a mixture containing Li(+), Na(+), K(+),
      Rb(+) and Cs(+); this can be indicative of pseudo-crown ether performance of the
      dumbbell. One interesting possibility is that the [COSAN](-) anions at the two
      ends of the linker can act as a hook-and-loop fastener to close the ring. This
      facet is intriguing and deserves further consideration for possible applications.
      The distinct affinity towards alkaline metal ions is corroborated by solubility
      studies and isothermal calorimetry thermograms. Furthermore, cryoTEM micrographs,
      along with light scattering results, reveal the existence of small self
      assemblies and compact nanostructures ranging from spheres to single-/multi-layer
      vesicles in aqueous solutions. The studies reported herein show that these
      dumbbells can have different appearances, either as molecules or aggregates, in
      water or lipophilic phases; this offers a distinct model as drug carriers.

PMID- 24737690
TI  - Chromosome 17/17q gain and unaltered profiles in high resolution array-CGH are
      prognostically informative in neuroblastoma.
AB  - The prognostic relevance of chromosome 17 gain in neuroblastoma is still
      discussed. This investigation specifies the frequency, type, size, and
      transcriptional relevance in a large patient cohort. Primary tumor material of
      202 patients was analyzed using high-resolution oligonucleotide array-based
      comparative genomic hybridization (aCGH) and correlated with clinical and
      survival data. A subset (n = 145) was correlated for differentially expressed
      genes (DEG) by microarray analysis. Chromosome 17 aCGH analysis showed numerical
      gain in 94/202 patients (47%), partial gain in 93/202 patients (46%), and no gain
      in 15/202 patients (7%). The frequency of partial gain was higher in stage 4
      neuroblastoma (stage 1 15%; stage 2 12%; stage 3 16%; stage 4S 7%; and stage 4
      50%). Overall survival (OS) was superior in patients with numerical gain compared
      with patients with partial gain or no gain (5-y-OS: 0.95 +/- 0.02 vs. 0.63 +/-
      0.05 vs. 0.60 +/- 0.13; P < 0.001). Gene expression analysis demonstrated 95/130
      DEGs between tumors with numerical or partial chromosome/no gain. Only one DEG
      (CCKBR) was detected comparing tumors with partial gain and those with no gain.
      In patients with partial gain, the distribution of breakpoints did not correlate
      with stage and 11q status, but with MYCN amplification and 1p status. The "best"
      breakpoints in cases with partial 17q gain were at 42.5 Mb for event-free and
      26.6 Mb for OS. Numerical gain of chromosome 17 is associated with a better
      prognosis than partial and no gain. The group of tumors with partial gain was
      similar to the group without gain with respect to stage distribution, outcome,
      and gene expression profile.

PMID- 24737691
TI  - Multi-walled carbon nanotube modified dummy-template magnetic molecularly
      imprinted microspheres as solid-phase extraction material for the determination
      of polychlorinated biphenyls in fish.
AB  - Novel multi-walled carbon nanotube modified dummy-template molecularly imprinted
      microspheres (MWCNTs@DMMIPs) were successfully synthesized as adsorbents for six
      kinds of polychlorinated biphenyls (PCBs). MWCNTs@DMMIPs were prepared by a
      surface molecular imprinting technique. Core-shell Fe3 O4 @SiO2 nanoparticles
      were employed as magnetic support. 3,4-Dichlorobenzene acetic acid was used as a
      dummy template instead of PCBs, methacrylic acid was used as functional monomer
      and ethylene glycol dimethacrylate was used as the cross-linker. The resulting
      absorbent was characterized by various methods. The adsorbent was employed for
      extracting PCBs and exhibited good selectivity and high adsorption efficiency.
      Furthermore, it was reusable and capable of magnetic separation. Adsorption
      kinetics fit well with a pseudo-second-order kinetic equation and also exhibited
      a three-stage intra-particle diffusion model. The Freundlich model was used to
      describe the adsorption isotherms. The materials were successfully applied to the
      magnetic dispersive solid-phase extraction of six kinds of PCBs followed by gas
      chromatography with mass spectrometry determination in fish samples, the limit of
      detection of six kinds of PCBs were 0.0028-0.0068 MUg/L and spiked recoveries
      ranged between 73.41 and 114.21%. The prepared adsorbent was expected to be a new
      material for the removal and recovery of PCBs from contaminated foods. 

PMID- 24737692
TI  - Asymmetric catalysis on the nanoscale: the organocatalytic approach to helicenes.
AB  - The first asymmetric organocatalytic synthesis of helicenes is reported. A novel
      SPINOL-derived phosphoric acid, bearing extended pi-substituents, catalyzes the
      asymmetric synthesis of helicenes through an enantioselective Fischer indole
      reaction. A variety of azahelicenes and diazahelicenes could be obtained with
      good to excellent yields and enantioselectivities. 

PMID- 24737694
TI  - Bone forming capacity of cell- and growth factor-based constructs at different
      ectopic implantation sites.
AB  - The aim of this study was to compare the effect of implantation site (i.e.,
      subcutaneous, SQ vs. intramuscular, IM) on bone forming capacity of cell-based
      and growth factor-based scaffolds in athymic nude rats after an implantation
      period of 8 weeks. Cell-based scaffolds consisted of porous
      hydroxyapatite/tricalcium phosphate (HA/TCP) scaffolds seeded with either human
      adipose tissue-derived mesenchymal stem cells (AT-MSCs) only or both AT-MSCs and
      human umbilical vein endothelial cells (HUVECs), which were precultured in
      osteogenic medium for 7 days. Growth factor-based scaffolds consisted of porous
      HA/TCP scaffolds with 20 ug preadsorbed bone morphogenetic protein-2 (BMP-2).
      Histological and histomorphometrical analysis were used to assess bone formation.
      A differentiation experiment was performed in parallel to compare the in vitro
      osteogenic capacity of cell-based scaffolds. The results showed that cell-based
      scaffolds showed evident osteogenic differentiation in vitro, with only marginal
      differences between AT-MSCs only and AT-MSCs/HUVECs. In vivo, none of the cell
      based scaffolds showed bone formation, irrespective of the site of implantation.
      In contrast, all growth factor-based scaffolds showed bone formation at both
      implantation sites without differences in the amount of formed bone. In
      conclusion, the results of this study demonstrated that the bone forming capacity
      of HA/TCP scaffolds with pre-adsorbed BMP-2 was equal at different ectopic
      implantation sites. Further, despite obvious in vitro osteogenic differentiation
      of AT-MSCs and AT-MSCS/HUVECs on HA/TCP scaffolds, no bone formation of these
      cell-based scaffolds was observed in vivo. This indicates further investigation
      on bone formation mechanisms of AT-MSCs is needed before AT-MSCs can be used as a
      cytotherapeutic treatment in clinics.

PMID- 24737695
TI  - Functional streams and cortical integration in the human brain.
AB  - The processing of brain information relies on the organization of neuronal
      networks and circuits that in the end must provide the substrate for human
      cognition. However, the presence of highly complex and multirelay neuronal
      interactions has limited our ability to disentangle the assemblies of brain
      systems. The present review article focuses on the latest developments to
      understand the architecture of functional streams of the human brain at the large
      scale level. Particularly, this article presents a comprehensive framework and
      recent findings about how the highly modular sensory cortex, such as the visual,
      somatosensory, auditory, as well as motor cortex areas, connects to more parallel
      organized cortical hubs in the brain's functional connectome. 

PMID- 24737693
TI  - Nanoparticulate delivery of agents for induced elastogenesis in three-dimensional
      collagenous matrices.
AB  - The degradation of elastic matrix in the infrarenal aortic wall is a critical
      parameter underlying the formation and progression of abdominal aortic aneurysms.
      It is mediated by the chronic overexpression of matrix metalloprotease (MMP)-2
      and MMP-9, leading to a progressive loss of elasticity and weakening of the
      aortic wall. Delivery of therapeutic agents to inhibit MMPs, while concurrently
      coaxing cell-based regenerative repair of the elastic matrix represents a
      potential strategy for slowing or arresting abdominal aortic aneurysm growth.
      Previous studies have demonstrated elastogenic induction of healthy and
      aneurysmal aortic smooth muscle cells and inhibition of MMPs, following exogenous
      delivery of elastogenic factors such as transforming growth factor (TGF)-beta1,
      as well as MMP-inhibitors such as doxycycline (DOX) in two-dimensional culture.
      Based on these findings, and others that demonstrated elastogenic benefits of
      nanoparticulate delivery of these agents in two-dimensional culture, poly(lactide
      co-glycolide) nanoparticles were developed for localized, controlled and
      sustained delivery of DOX and TGF-beta1 to human aortic smooth muscle cells
      within a three-dimensional gels of type I collagen, which closely simulate the
      arterial tissue microenvironment. DOX and TGF-beta1 released from these
      nanoparticles influenced elastogenic outcomes positively within the collagen
      constructs over 21 days of culture, which were comparable to that induced by
      exogenous supplementation of DOX and TGF-beta1 within the culture medium.
      However, this was accomplished at doses ~20-fold lower than the exogenous dosages
      of the agents, illustrating that their localized, controlled and sustained
      delivery from nanoparticles embedded within a three-dimensional scaffold is an
      efficient strategy for directed elastogenesis. Copyright (c) 2014 John Wiley &
      Sons, Ltd.

PMID- 24737696
TI  - Overexpression of Banna mini-pig inbred line fatty acid binding protein 3
      promotes adipogenesis in 3T3-L1 preadipocytes.
AB  - Fatty acid binding protein 3 (H-FABP, FABP3) has been significantly associated
      with intramuscular fat (IMF) content in pigs, which is positively correlated with
      palatability of pork. However, its underlying function is not fully elucidated.
      We have investigated the effects of overexpression of the FABP3 gene on
      differentiation and adipogenesis of 3T3-L1 preadipocytes in the fat Banna mini
      pig inbred line (fBMIL). Eukaryotic vectors that expressed the FABP3 protein were
      constructed, and stably established in the 3T3-L1 preadipocytes cell line. Cells
      were induced in a standard differentiation cocktail. Morphological changes and
      the degree of adipogenesis were measured by Oil Red O staining assay and
      triacylglycerol content measurement, respectively. mRNA expression levels of
      triacylglycerol metabolism-related genes were measured by qPCR. FABP3
      significantly promoted differentiation of 3T3-L1 cells and enhanced
      triacylglycerol levels (P < 0.05). mRNA of the peroxisome proliferator-activated
      receptor gamma (PPARgamma), adipocyte fatty acid binding protein (422/aP2) and
      glycerol-3-phosphate dehydrogenase (GPDH) gene increased markedly (P < 0.05). In
      conclusion, expression of the FABP3 gene enhances adipogenesis in 3T3-L1
      preadipocytes primarily by upregulating lipogenic PPARgamma, 422/aP2 and GPDH
      genes.

PMID- 24737699
TI  - Lubricin: a novel means to decrease bacterial adhesion and proliferation.
AB  - This study investigated the ability of lubricin (LUB) to prevent bacterial
      attachment and proliferation on model tissue culture polystyrene surfaces. The
      findings from this study indicated that LUB was able to reduce the attachment and
      growth of Staphylococcus aureus on tissue culture polystyrene over the course of
      24 h by approximately 13.9% compared to a phosphate buffered saline (PBS)-soaked
      control. LUB also increased S. aureus lag time (the period of time between the
      introduction of bacteria to a new environment and their exponential growth) by
      approximately 27% compared to a PBS-soaked control. This study also indicated
      that vitronectin (VTN), a protein homologous to LUB, reduced bacterial S. aureus
      adhesion and growth on tissue culture polystyrene by approximately 11% compared
      to a PBS-soaked control. VTN also increased the lag time of S. aureus by
      approximately 43%, compared to a PBS-soaked control. Bovine submaxillary mucin
      was studied because there are similarities between it and the center mucin-like
      domain of LUB. Results showed that the reduction of S. aureus and Staphylococcus
      epidermidis proliferation on mucin coated surfaces was not as substantial as that
      seen with LUB. In summary, this study provided the first evidence that LUB
      reduced the initial adhesion and growth of both S. aureus and S. epidermidis on a
      model surface to suppress biofilm formation. These reductions in initial bacteria
      adhesion and proliferation can be beneficial for medical implants and, although
      requiring more study, can lead to drastically improved patient outcomes.

PMID- 24737700
TI  - Determination of genetic transferrin variants in human serum by high-resolution
      capillary zone electrophoresis(?).
AB  - High-resolution capillary zone electrophoresis in the routine arena with
      stringent quality assurance is employed for the determination of carbohydrate
      deficient transferrin in human serum. The assay comprises mixing of human serum
      with a Fe(III) -containing solution prior to analysis of the iron-saturated
      mixture in a dynamically double-coated capillary using a commercial buffer at
      alkaline pH. In contrast to other assays, it provides sufficient resolution for
      proper recognition of genetic transferrin variants. Analysis of 7290 patient sera
      revealed 166 isoform patterns that could be assigned to genetic variants, namely,
      109 BC, 53 CD, one BD and three CC variants. Several subtypes of transferrin D
      can be distinguished as they have large enough differences in pI values. Subtypes
      of transferrin C and B cannot be resolved. However, analysis of the detection
      time ratios of tetrasialo isoforms of transferrin BC and transferrin CD variants
      revealed multimodal frequency histograms, indicating the presence of subtypes of
      transferrin C, B and D. The data gathered over 11 years demonstrate the
      robustness of the high-resolution capillary zone electrophoresis assay. This is
      the first account of a capillary zone electrophoresis based carbohydrate
      deficient transferrin assay with a broad overview on transferrin isoform patterns
      associated with genetic transferrin variants. 

PMID- 24737701
TI  - Oxidative addition of water and methanol to a dicationic trivalent phosphorus
      centre.
AB  - Our recently synthesised phosphorus dication is observed to activate water (and
      methanol) under reactions conditions atypical for other systems containing a non
      metal centre. This particular activation described as oxidative addition is quite
      rare and has been reserved exclusively for a couple of metal-based compounds. 

PMID- 24737703
TI  - The social context of the relationship between glycemic control and depressive
      symptoms in type 2 diabetes.
AB  - OBJECTIVE: Individuals with type 2 diabetes and depressive symptoms have poorer
      diabetes outcomes than those with diabetes alone, and there is need for improved
      understanding of the relationship between illness markers and depressive
      symptoms. The role of social support is well established; less is known about
      social comparisons (i.e. comparisons to others in the social environment), which
      are common and influential in chronic illness. The present study examined the
      mediating effects of social comparison and social support on the relationship
      between glycemic control and depressive symptoms. METHOD AND OUTCOME MEASURES:
      Participants with physician-diagnosed type 2 diabetes (N = 185) completed an
      electronic survey about recent depressive symptoms, glycemic control (HbA1c),
      perceived social support, and social comparison. RESULTS: Controlling for
      relevant covariates, social comparison and social support showed independent
      statistical mediation of the relationship between glycemic control and depressive
      symptoms (ps < 0.05). Path analysis also showed that including indirect pathways
      through social comparison and social support reduced the relationship between
      glycemic control and depressive symptoms to nonsignificance (beta = 0.10, p =
      0.14). CONCLUSION: These findings demonstrate that social comparison plays a role
      in the relationship between diabetes regulation and depression, independent of
      social support. Greater attention to this aspect of the social environment may
      render better diabetes outcomes.

PMID- 24737702
TI  - Improved physiological properties of gravity-enforced reassembled rat and human
      pancreatic pseudo-islets.
AB  - Previously we demonstrated the superiority of small islets vs large islets in
      terms of function and survival after transplantation, and we generated
      reaggregated rat islets (pseudo-islets) of standardized small dimensions by the
      hanging-drop culture method (HDCM). The aim of this study was to generate human
      pseudo-islets by HDCM and to evaluate and compare the physiological properties of
      rat and human pseudo-islets. Isolated rat and human islets were dissociated into
      single cells and incubated for 6-14 days by HDCM. Newly formed pseudo-islets were
      analysed for dimensions, morphology, glucose-stimulated insulin secretion (GSIS)
      and total insulin content. The morphology of reaggregated human islets was
      similar to that of native islets, while rat pseudo-islets had a reduced content
      of alpha and delta cells. GSIS of small rat and human pseudo-islets (250 cells)
      was increased up to 4.0-fold (p < 0.01) and 2.5-fold (p < 0.001), respectively,
      when compared to their native counterparts. Human pseudo-islets showed a more
      pronounced first-phase insulin secretion as compared to intact islets. GSIS was
      inversely correlated to islet size, and small islets (250 cells) contained up to
      six-fold more insulin/cell than large islets (1500 cells). Tissue loss with this
      new technology could be reduced to 49.2 +/- 1.5% in rat islets, as compared to
      the starting amount. With HDCM, pseudo-islets of standardized size with similar
      cellular composition and improved biological function can be generated, which
      compensates for tissue loss during production. Transplantation of small pseudo
      islets may represent an attractive strategy to improve graft survival and
      function, due to better oxygen and nutrient supply during the phase of
      revascularization. Copyright (c) 2014 John Wiley & Sons, Ltd.

PMID- 24737704
TI  - Inhibition of ASICs reduces rat hepatic stellate cells activity and liver
      fibrosis: an in vitro and in vivo study.
AB  - Hepatic fibrosis is a chronic inflammation-associated disease, which is involved
      in the infiltration of inflammatory cells and releasing of proinflammatory
      cytokines. In the pathological process, protons are released by damaged cells and
      acidosis is considered to play a critical role in cell injury. Although the
      underlying mechanism (s) remain ill-defined, ASICs (acid-sensing ion channels)
      are assumed to be involved in this process. The diuretic, amiloride, is
      neuroprotective in models of cerebral ischemia, a property attributable to the
      inhibition of central ASICs by the drug. However, the effect of inhibition of
      ASICs by amiloride in the liver fibrotic process remains unclear. We found that
      amiloride (25, 50, or 100 MUM) could restrain acid-induced HSCs at pH6 in vitro.
      In vivo experiments showed that amiloride could significantly alleviate liver
      injury, decreasing levels of profibrogenic cytokines, collagen deposition, and
      reducing pathological tissue damage. In summary, amiloride inhibits hepatic
      fibrosis in vivo and in vitro, which is probably associated with the
      downregulation of ASICs.

PMID- 24737705
TI  - A novel type of luciferin from the Siberian luminous earthworm Fridericia
      heliota: structure elucidation by spectral studies and total synthesis.
AB  - The structure elucidation and synthesis of the luciferin from the recently
      discovered luminous earthworm Fridericia heliota is reported. This luciferin is a
      key component of a novel ATP-dependent bioluminescence system. UV, fluorescence,
      NMR, and HRMS spectroscopy studies were performed on 0.005 mg of the isolated
      substance and revealed four isomeric structures that conform to spectral data.
      These isomers were chemically synthesized and one of them was found to produce
      light when reacted with a protein extract from F. heliota. The novel luciferin
      was found to have an unusual extensively modified peptidic nature, thus implying
      an unprecedented mechanism of action. 

PMID- 24737706
TI  - Silicon calcium phosphate ceramic as novel biomaterial to simulate the bone
      regenerative properties of autologous bone.
AB  - This study was conducted to develop novel ceramic bone substitute that resembles
      the autologous bone behavior when used as graft material. Solid-state reaction at
      1100 degrees C was performed to synthesize beta-tricalcium phosphate (beta-TCP)
      and biphasic calcium phosphate (BCP). The ceramics were further analyzed to
      characterize phase composition, microstructural properties, cytocompatability and
      then challenged to regenerate critical bone defects in the parietal bone of
      rabbits. X-ray diffraction analysis confirmed the production of beta-TCP and
      indicated the synthesis of novel BCP composed of beta-TCP and silicocarnotite
      (calcium phosphate silicate mineral). The cytocompatibility test with human
      osteoblast cell line revealed enhanced cell proliferation on the BCP ceramic. The
      novel BCP induced the filling of about 73% of the bone defect with a newly formed
      bone tissue and an almost complete degradation after 12 weeks of healing. This
      novel ceramic resembles the autologous bone properties of complete degradation
      and efficient enhancement of bone formation, making it promising as bone graft
      material.

PMID- 24737707
TI  - Effect of biomimetic zinc-containing tricalcium phosphate (Zn-TCP) on the growth
      and osteogenic differentiation of mesenchymal stem cells.
AB  - Several studies have shown the effectiveness of zinc-tricalcium phosphate (Zn
      TCP) for bone tissue engineering. In this study, marine calcareous foraminifera
      possessing uniform pore size distribution were hydrothermally converted to Zn
      TCP. The ability of a scaffold to combine effectively with mesenchymal stem cells
      (MSCs) is a key tissue-engineering aim. In order to demonstrate the osteogenic
      ability of MSCs with Zn-TCP, the scaffolds were cultured in an osteogenic
      induction medium to elicit an osteoblastic response. The physicochemical
      properties of Zn-TCP were characterized by XRD, FT-IR and ICP-MS. MSCs were
      aspirated from rat femurs and cultured for 3 days before indirectly placing four
      samples into each respective well. After culture for 7, 10 and 14 days,
      osteoblastic differentiation was evaluated using alizarin red S stain,
      measurement of alkaline phosphatase (ALP) levels, cell numbers and cell
      viability. XRD and FT-IR patterns both showed the replacement of CO(3)(2-) with
      PO(4)(3-). Chemical analysis showed zinc incorporation of 5 mol%. Significant
      increases in cell numbers were observed at 10 and 14 days in the Zn-TCP group,
      while maintaining high levels of cell viability (> 90%). ALP activity in the Zn
      TCP group was statistically higher at 10 days. Alizarin red S staining also
      showed significantly higher levels of calcium mineralization in Zn-TCP compared
      with the control groups. This study showed that MSCs in the presence of
      biomimetically derived Zn-TCP can accelerate their differentiation to osteoblasts
      and could potentially be useful as a scaffold for bone tissue engineering.

PMID- 24737708
TI  - Coronavirus entry and release in polarized epithelial cells: a review.
AB  - Most coronaviruses cause respiratory or intestinal infections in their animal or
      human host. Hence, their interaction with polarized epithelial cells plays a
      critical role in the onset and outcome of infection. In this paper, we review the
      knowledge regarding the entry and release of coronaviruses, with particular
      emphasis on the severe acute respiratory syndrome and Middle East respiratory
      syndrome coronaviruses. As these viruses approach the epithelial surfaces from
      the apical side, it is not surprising that coronavirus cell receptors are exposed
      primarily on the apical domain of polarized epithelial cells. With respect to
      release, all possibilities appear to occur. Thus, most coronaviruses exit through
      the apical surface, several through the basolateral one, although the Middle East
      respiratory syndrome coronavirus appears to use both sides. These observations
      help us understand the local or systematic spread of the infection within its
      host as well as the spread of the virus within the host population.

PMID- 24737709
TI  - Large zero-field splittings of the ground spin state arising from antisymmetric
      exchange effects in heterometallic triangles.
AB  - [Ru2Mn(O)(O2CtBu)6(py)3] has an S=5/2 ground state with a very large zero-field
      splitting (ZFS) of D=2.9 cm(-1), as characterized by EPR spectroscopy at 4-330
      GHz. This is far too large to be due to the Mn(II) ion (D <0.2 cm(-1)), as shown
      from the {Fe2Mn} analogue, but can be modeled by antisymmetric exchange effects.

PMID- 24737711
TI  - An easy route to (hetero)arylboronic acids.
AB  - An unprecedented spontaneous reactivity between diazonium salts and diboronic
      acid has been unveiled, leading to a versatile arylboronic acid synthesis
      directly from (hetero)arylamines. This fast reaction (35 min overall) tolerates a
      wide range of functional groups and is carried out under very mild conditions.
      The radical nature of the reaction mechanism has been investigated.

PMID- 24737710
TI  - Early life trauma and directional brain connectivity within major depression.
AB  - OBJECTIVE: Early life trauma (ELT) is a significant risk factor for the onset of
      depression. Emerging findings indicate ELT is associated with enhanced amygdala
      reactivity to aversive stimuli in never-depressed healthy controls as well as
      those with acute depression but may be absent in non-ELT exposed depressed. The
      precise mechanism mediating these differences in amygdala reactivity remains
      unclear. METHOD: The authors used Granger causality methods to evaluate task
      based directional connectivity between medial or lateral prefrontal cortex (PFC)
      and amygdala in 20 unmedicated patients with current major depressive disorder
      (MDD) and 19 healthy matched controls while participants engaged in an affective
      variant of the flanker task comparing response to sad and neutral faces. These
      data were correlated with childhood trauma history. RESULTS: Exposure to ELT was
      associated with failure of inhibition within the MDD group based on medial PFC
      amygdala connectivity. In contrast, non-ELT exposed MDD was associated with a
      negative causal pathway from medial prefrontal cortex to amygdala, despite
      reduced dorsolateral PFC input in comparison to healthy controls. Neither MDD
      group demonstrated significant lateral PFC-amygdala connectivity in comparison to
      healthy controls. CONCLUSIONS: Failure of the circuit implicated in emotion
      regulation was associated with a significant history of ELT but not with MDD more
      broadly. Non-ELT related depression was associated with intact regulation of
      emotion despite the absence of difference in severity of illness. These findings
      indicate opposing system-level differences within depression relative to ELT are
      expressed as differential amygdala reactivity.

PMID- 24737712
TI  - Lipids, safety parameters, and drug concentrations after an additional 2 years of
      treatment with anacetrapib in the DEFINE study.
AB  - Anacetrapib is a cholesteryl ester transfer protein (CETP) inhibitor that has
      previously been shown to reduce low-density lipoprotein cholesterol (LDL-C) and
      raise high-density lipoprotein cholesterol (HDL-C) in patients with or at high
      risk of coronary heart disease in the 76-week, placebo-controlled, Determining
      the Efficacy and Tolerability of CETP Inhibition with Anacetrapib (DEFINE) trial.
      Here, we report the results of the 2-year extension to the DEFINE study where
      patients (n = 803) continued on the same assigned treatment as in the original 76
      week study. Treatment with anacetrapib during the 2-year extension was well
      tolerated with a safety profile similar to patients on placebo. No clinically
      important abnormalities in liver enzymes, blood pressure, electrolytes, or
      adverse experiences were observed during the extension. At the end of the
      extension study, relative to the original baseline value, anacetrapib reduced
      Friedewald-calculated LDL-C by 39.9% and increased HDL-C by 153.3%, compared to
      placebo. The apparent steady state mean plasma trough concentration of
      anacetrapib was ~640 nmol/L. Geometric mean plasma concentrations of anacetrapib
      did not appear to increase beyond week 40 of the 2-year extension of the 76-week
      DEFINE base study. In conclusion, an additional 2 years of treatment with
      anacetrapib were well tolerated with durable lipid-modifying effects on LDL-C and
      HDL-C. 

PMID- 24737713
TI  - The cell-engineered construct of cartilage on the basis of biopolymer hydrogel
      matrix and human adipose tissue-derived mesenchymal stromal cells (in vitro
      study).
AB  - The study results of in vitro formation of tissue-engineered cartilage construct
      on the basis of cell-engineered construct composed of biopolymer hydrogel matrix
      and human adipose tissue-derived mesenchymal stromal cells (hADSCs) are
      presented. It was revealed that hADSCs in biopolymer hydrogel matrix Sphero(r)GEL
      under chondrogenic conditions generate three-dimensional structures and produce
      cartilaginous extracellular matrix components: collagen type II and
      glycosaminoglycans.

PMID- 24737715
TI  - Three-dimensional ordered assembly of thin-shell Au/TiO2 hollow nanospheres for
      enhanced visible-light-driven photocatalysis.
AB  - An Au/TiO(2) nanostructure was constructed to obtain a highly efficient visible
      light-driven photocatalyst. The design was based on a three-dimensional ordered
      assembly of thin-shell Au/TiO(2) hollow nanospheres (Au/TiO(2)-3 DHNSs). The
      designed photocatalysts exhibit not only a very high surface area but also
      photonic behavior and multiple light scattering, which significantly enhances
      visible-light absorption. Thus Au/TiO(2)-3 DHNSs exhibit a visible-light-driven
      photocatalytic activity that is several times higher than conventional Au/TiO(2)
      nanopowders.

PMID- 24737714
TI  - Development and characterization of novel agar and gelatin injectable hydrogel as
      filler for peripheral nerve guidance channels.
AB  - Injectable hydrogels are becoming of increasing interest in the field of tissue
      engineering thanks to their versatile properties and to the possibility of being
      injected into tissues or devices during surgery. In peripheral nerve tissue
      engineering, injectable hydrogels having shear-thinning properties are
      advantageous as filler of nerve guidance channels (NGCs) to improve the
      regeneration process. In the present work, gelatin-based hydrogels were developed
      and specifically designed for the insertion into the lumen of hollow NGCs through
      a syringe during surgery. Injectable hydrogels were obtained using an agar
      gelatin 20:80 weight ratio, (wt/wt) blend crosslinked by the addition of genipin
      (A/GL_GP). The physicochemical properties of the A/GL_GP hydrogels were analysed,
      including their injectability, rheological, swelling and dissolution behaviour,
      and their mechanical properties under compression. The hydrogel developed showed
      shear-thinning properties and was applied as filler of NGCs. The A/GL_GP hydrogel
      was tested in vitro using different cell lines, among them Schwann cells which
      have been used because they have an important role in peripheral nerve
      regeneration. Viability assays demonstrated the lack of cytotoxicity. In vitro
      experiments showed that the hydrogel is able to promote cell adhesion and
      proliferation. Two- and three-dimensional migration assays confirmed the
      capability of the cells to migrate both on the surface and within the internal
      framework of the hydrogel. These data show that A/GL_GP hydrogel has
      characteristics that make it a promising scaffold material for tissue engineering
      and nerve regeneration. Copyright (c) 2014 John Wiley & Sons, Ltd.

PMID- 24737716
TI  - Introgression of a 4D chromosomal fragment into durum wheat confers aluminium
      tolerance.
AB  - BACKGROUND AND AIM: Aluminium (Al(3+)) inhibits root growth of sensitive plant
      species and is a key factor that limits durum wheat (Triticum turgidum)
      production on acid soils. The aim of this study was to enhance the Al(3+)
      tolerance of an elite durum cultivar by introgression of a chromosomal fragment
      from hexaploid wheat (Triticum aestivum) that possesses an Al(3+) tolerance gene.
      METHODS: A 4D(4B) substitution line of durum wheat 'Langdon' was backcrossed to
      'Jandaroi', a current semi-dwarf Australian durum. In the second backcross, using
      'Jandaroi' as the recurrent parent, a seedling was identified where TaALMT1 on
      chromosome 4D was recombined with the Rht-B1b locus on chromosome 4B to yield an
      Al(3+)-tolerant seedling with a semi-dwarf habit. This seedling was used in a
      third backcross to generate homozygous sister lines with contrasting Al(3+)
      tolerances. The backcrossed lines were characterized and compared with selected
      cultivars of hexaploid wheat for their Al(3+) and Na(+) tolerances in hydroponic
      culture as well as in short-term experiments to assess their growth on acid soil.
      KEY RESULTS: Analysis of sister lines derived from the third backcross showed
      that the 4D chromosomal fragment substantially enhanced Al(3+) tolerance. The
      ability to exclude Na(+) from leaves was also enhanced, indicating that the
      chromosomal fragment possessed the Kna1 salt tolerance locus. Although Al(3+)
      tolerance of seminal roots was enhanced in acid soil, the development of fine
      roots was not as robust as found in Al(3+)-tolerant lines of hexaploid wheat.
      Analysis of plant characteristics in the absence of Al(3+) toxicity showed that
      the introgressed fragment did not affect total grain yield but reduced the weight
      of individual grains. CONCLUSIONS: The results show that it is possible to
      increase substantially the Al(3+) tolerance of an elite durum wheat cultivar by
      introgression of a 4D chromosomal fragment. Further improvements are possible,
      such as introducing additional genes to enhance the Al(3+) tolerance of fine
      roots and by eliminating the locus on the chromosomal fragment responsible for
      smaller grain weights.

PMID- 24737717
TI  - SNARE VTI13 plays a unique role in endosomal trafficking pathways associated with
      the vacuole and is essential for cell wall organization and root hair growth in
      arabidopsis.
AB  - BACKGROUND AND AIMS: Root hairs are responsible for water and nutrient uptake
      from the soil and their growth is responsive to biotic and abiotic changes in
      their environment. Root hair expansion is a polarized process requiring secretory
      and endosomal pathways that deliver and recycle plasma membrane and cell wall
      material to the growing root hair tip. In this paper, the role of VTI13
      (AT3G29100), a member of the VTI vesicular soluble NSF attachment receptor
      (SNARE) gene family in Arabidopsis thaliana, in root hair growth is described.
      METHODS: Genetic analysis and complementation of the vti13 root hair phenotypes
      of Arabidopsis thaliana were first used to assess the role of VTI13 in root hair
      growth. Transgenic lines expressing a green fluorescent protein (GFP)-VTI13
      construct were used to characterize the intracellular localization of VTI13 in
      root hairs using confocal microscopy and immunotransmission electron microscopy.
      KEY RESULTS: VTI13 was characterized and genetic analysis used to show that its
      function is required for root hair growth. Expression of a GFP-VTI13 fusion in
      the vti13 mutant background was shown to complement the vti13 root hair
      phenotype. GFP-VTI13 localized to both the vacuole membrane and a mobile
      endosomal compartment. The function of VTI13 was also required for the
      localization of SYP41 to the trans-Golgi network. Immunohistochemical analysis
      indicated that cell wall organization is altered in vti13 root hairs and root
      epidermal cells. CONCLUSIONS: These results show that VTI13 plays a unique role
      in endosomal trafficking pathways associated with the vacuole within root hairs
      and is essential for the maintenance of cell wall organization and root hair
      growth in arabidopsis.

PMID- 24737718
TI  - Spatial genetic structure reflects extensive clonality, low genotypic diversity
      and habitat fragmentation in Grevillea renwickiana (Proteaceae), a rare, sterile
      shrub from south-eastern Australia.
AB  - BACKGROUND AND AIMS: The association of clonality, polyploidy and reduced
      fecundity has been identified as an extinction risk for clonal plants.
      Compromised sexual reproduction limits both their ability to adapt to new
      conditions and their capacity to disperse to more favourable environments.
      Grevillea renwickiana is a prostrate, putatively sterile shrub reliant on asexual
      reproduction. Dispersal is most likely limited by the rate of clonal expansion
      via rhizomes. The nine localized populations constituting this species provide an
      opportunity to examine the extent of clonality and spatial genotypic diversity to
      evaluate its evolutionary prospects. METHODS: Ten microsatellite loci were used
      to compare genetic and genotypic diversity across all sites with more intensive
      sampling at four locations (n = 185). The spatial distribution of genotypes and
      chloroplast DNA haplotypes based on the trnQ-rps16 intergenic spacer region were
      compared. Chromosome counts provided a basis for examining genetic profiles
      inconsistent with diploidy. KEY RESULTS: Microsatellite analysis identified 46
      multilocus genotypes (MLGs) in eight multilocus clonal lineages (MLLs). MLLs are
      not shared among sites, with two exceptions. Spatial autocorrelation was
      significant to 1.6 km. Genotypic richness ranged from 0 to 0.33. Somatic mutation
      is likely to contribute to minor variation between MLGs within clonal lineages.
      The eight chloroplast haplotypes identified were correlated with eight MLLs
      defined by ordination and generally restricted to single populations. Triploidy
      is the most likely reason for tri-allelic patterns. CONCLUSIONS: Grevillea
      renwickiana comprises few genetic individuals. Sterility has most likely been
      induced by triploidy. Extensive lateral suckering in long-lived sterile clones
      facilitates the accumulation of somatic mutations, which contribute to the
      measured genetic diversity. Genetic conservation value may not be a function of
      population size. Despite facing evolutionary stagnation, sterile clonal species
      can play a vital role in mitigating ecological instability as floras respond to
      rapid environmental change.

PMID- 24737719
TI  - Comparative anatomy of floral elaiophores in Vitekorchis Romowicz & Szlach.,
      Cyrtochilum Kunth and a florally dimorphic species of Oncidium Sw. (Orchidaceae:
      Oncidiinae).
AB  - BACKGROUND AND AIMS: Recently, molecular approaches have been used to investigate
      the phylogeny of subtribe Oncidiinae, resulting in the re-alignment of several of
      its genera. Here, a description is given of the structure of the floral
      elaiophores (oil glands) of four species formerly assigned to Oncidium Sw. Those
      of Vitekorchis excavata (Lindl.) Romowicz & Szlach., Cyrtochilum meirax (Rchb.f.)
      Dalstrom and a species of Oncidium displaying floral dimorphism, namely O.
      heteranthum Poepp. & Endl. var. album, are compared with that of Gomesa longipes
      (Lindl.) M.W. Chase & N.H. Williams, whose epithelial elaiophores are typical of
      many Oncidiinae, in order to extend our understanding of elaiophore diversity
      within this subtribe. METHODS: Floral elaiophore structure was examined and
      compared at anthesis for all four species using light microscopy, scanning
      electron microscopy, transmission electron microscopy and histochemistry. KEY
      RESULTS: In all species investigated, with the exception of C. meirax, the floral
      elaiophore occurs on the labellar callus and is of the intermediate type,
      possessing both glabrous and trichomatous regions. By contrast, although all four
      species produce lipid secretions, C. meirax lacks an obvious elaiophore. In each
      case, the secretory tissue is represented by a single-layered epidermis of
      cuboidal cells (trichomatous and/or atrichomatous). Palisade cells are absent.
      The secretion may be wax- or oil-like and is usually produced by smooth
      endoplasmic reticulum (SER). However, in C. meirax, where rough endoplasmic
      reticulum (RER) predominates, oil accumulates as plastoglobuli within
      elaioplasts. These plastoglobuli are then discharged into the cytoplasm, forming
      oil bodies. In some species, oil usually accumulates within vesicles at the
      plasmalemma or in the periplasmic space before traversing the cell wall and
      accumulating beneath the cuticle, sometimes with distension of the latter. Gomesa
      longipes is unusual in its production of a heterogeneous secretion, whereas
      Vitekorchis excavata is equally remarkable for the protuberances found on the
      walls of its secretory cells. CONCLUSIONS: Anatomically, the secretory tissues of
      all four species, despite currently being assigned to four different genera, are
      remarkably similar and indicative of homoplasy. This supports previous
      investigations of the floral elaiophore in Oncidiinae, which showed that the same
      elaiophore characters may be shared by different clades, but not always by
      species of the same genus. Consequently, elaiophores are considered to be of
      limited value in investigating the phylogeny of this subtribe. Furthermore,
      floral dimorphism does not greatly modify elaiophore structure in the fertile
      flowers of Oncidium heteranthum var. album. Based on the presence or absence of
      well-defined elaiophores, the nature of the secretion and the cell
      ultrastructure, it is likely that floral oil may be produced in Oncidiinae in one
      of two ways: by the ER (mainly SER) or by plastids, most notably elaioplasts.
      Once the oil is discharged into the cytoplasm as oil bodies or oil droplets,
      there is little difference between the subsequent stages of oil secretion; the
      oil traversing the cytoplasm (often vesicle-mediated) and cell wall before
      accumulating beneath the cuticle.

PMID- 24737720
TI  - Genotype, development and tissue-derived variation of cell-wall properties in the
      lignocellulosic energy crop Miscanthus.
AB  - BACKGROUND AND AIMS: Species and hybrids of the genus Miscanthus contain
      attributes that make them front-runners among current selections of dedicated
      bioenergy crops. A key trait for plant biomass conversion to biofuels and
      biomaterials is cell-wall quality; however, knowledge of cell-wall composition
      and biology in Miscanthus species is limited. This study presents data on cell
      wall compositional changes as a function of development and tissue type across
      selected genotypes, and considers implications for the development of miscanthus
      as a sustainable and renewable bioenergy feedstock. METHODS: Cell-wall biomass
      was analysed for 25 genotypes, considering different developmental stages and
      stem vs. leaf compositional variability, by Fourier transform mid-infrared
      spectroscopy and lignin determination. In addition, a Clostridium phytofermentans
      bioassay was used to assess cell-wall digestibility and conversion to ethanol.
      KEY RESULTS: Important cell-wall compositional differences between miscanthus
      stem and leaf samples were found to be predominantly associated with structural
      carbohydrates. Lignin content increased as plants matured and was higher in stem
      tissues. Although stem lignin concentration correlated inversely with ethanol
      production, no such correlation was observed for leaves. Leaf tissue contributed
      significantly to total above-ground biomass at all stages, although the extent of
      this contribution was genotype-dependent. CONCLUSIONS: It is hypothesized that
      divergent carbohydrate compositions and modifications in stem and leaf tissues
      are major determinants for observed differences in cell-wall quality. The
      findings indicate that improvement of lignocellulosic feedstocks should encompass
      tissue-dependent variation as it affects amenability to biological conversion.
      For gene-trait associations relating to cell-wall quality, the data support the
      separate examination of leaf and stem composition, as tissue-specific traits may
      be masked by considering only total above-ground biomass samples, and sample
      variability could be mostly due to varying tissue contributions to total biomass.

PMID- 24737721
TI  - Topological methods reveal high and low functioning neuro-phenotypes within
      fragile X syndrome.
AB  - Fragile X syndrome (FXS), due to mutations of the FMR1 gene, is the most common
      known inherited cause of developmental disability as well as the most common
      single-gene risk factor for autism. Our goal was to examine variation in brain
      structure in FXS with topological data analysis (TDA), and to assess how such
      variation is associated with measures of IQ and autism-related behaviors. To this
      end, we analyzed imaging and behavioral data from young boys (n = 52; aged 1.57
      4.15 years) diagnosed with FXS. Application of topological methods to structural
      MRI data revealed two large subgroups within the study population. Comparison of
      these subgroups showed significant between-subgroup neuroanatomical differences
      similar to those previously reported to distinguish children with FXS from
      typically developing controls (e.g., enlarged caudate). In addition to
      neuroanatomy, the groups showed significant differences in IQ and autism severity
      scores. These results suggest that despite arising from a single gene mutation,
      FXS may encompass two biologically, and clinically separable phenotypes. In
      addition, these findings underscore the potential of TDA as a powerful tool in
      the search for biological phenotypes of neuropsychiatric disorders.

PMID- 24737722
TI  - Effects of Fab' fragments of specific egg yolk antibody (IgY-Fab') against
      Shewanella putrefaciens on the preservation of refrigerated turbot.
AB  - BACKGROUND: In our previous studies the specific egg yolk antibody (IgY) against
      Shewanella putrefaciens (one of the specific spoilage organisms for marine
      products during aerobic chilling storage) demonstrated significant activity to
      prolong the shelf life of refrigerated fish. The exploitation of the antigen
      binding fragment plus the hinge region (IgY-Fab') is now considered a promising
      method for improving the efficiency of such natural antimicrobial agents.
      RESULTS: The antimicrobial activity of IgY-Fab' against S. putrefaciens was
      investigated using refrigerated turbot as samples. By microbial, chemical and
      sensory tests, it was shown to be able to effectively inhibit bacterial growth
      and prolong the shelf life of samples, with an efficiency evaluated significantly
      higher than that of whole IgY with the same molarity. The interaction between IgY
      agents and S. putrefaciens cells was also investigated, and the IgY-Fab' showed a
      much greater ability to damage cell membranes than the whole IgY. CONCLUSION:
      Compared to whole IgY with the same molarity, IgY-Fab' demonstrated higher and
      more durable antimicrobial efficiency. Such a result was assumed to be closely
      related to its structural properties (such as the much lower molecular weight),
      which may enhance its ability to influence physiological activities of antigen
      bacteria, especially the property or/and structure of cell membranes.

PMID- 24737723
TI  - Hydroxyapatite-titanium bulk composites for bone tissue engineering applications.
AB  - The research work on bulk hydroxyapatite (HA)-based composites are driven by the
      need to develop biomaterials with better mechanical properties without
      compromising its bioactivity and biocompatibility properties. Despite several
      years of research, the mechanical properties of the HA-based composites still
      need to be enhanced to match the properties of natural cortical bone. In this
      regard, the scope of this review on the HA-based bulk biomaterials is limited to
      the processing and the mechanical as well as biocompatibility properties for bone
      tissue engineering applications of a model system that is hydroxyapatite-titanium
      (HA-Ti) bulk composites. It will be discussed in this review how HA-Ti based bulk
      composites can be processed to have better fracture toughness and strength
      without compromising biocompatibility. The advantages of the functionally
      gradient materials to integrate the mechanical and biocompatibility properties is
      a promising approach in hard tissue engineering and has been emphasized here in
      reference to the limited literature reports. On the biomaterials fabrication
      aspect, the recent results are discussed to demonstrate that advanced
      manufacturing techniques, like spark plasma sintering can be adopted as a
      processing route to restrict the sintering reactions, while enhancing the
      mechanical properties. Various toughening mechanisms related to careful tailoring
      of microstructure are discussed. The in vitro cytocompatibilty, cell fate
      processes as well as in vivo biocompatibility results are also reviewed and the
      use of flow cytometry to quantify in vitro cell fate processes is being
      emphasized.

PMID- 24737725
TI  - Ultrastructural features of vagina at different phases of the oestrous cycle in
      the female African giant rat (Cricetomys gambianus Waterhouse).
AB  - The ultrastructures of the vagina at various stages of the oestrous cycle in
      female African giant rats (Cricetomys gambianus Waterhouse) were described in the
      present study. At mid-proestrus, late proestrus (LP)/early estrus (EE) and mid
      estrus (ME) as well as late metestrus (LM)/early diestrus (ED) and mid-diestrus
      (MD), complex interface of epithelium and lamina propria were observed. Cells of
      the stratum basale formed finger-like extensions into the underlying lamina
      propria and tips of the extensions displayed hemidesmosome while basal lamina
      followed the contour of the extensions. At mid-metestrus (MM) and late
      diestrus/early proestrus, well developed, relatively straight basal lamina
      interfaced between the stratum basale and the lamina propria without finger-like
      projections. Polygonal cells with indented nuclei and, cytoplasm containing
      ribosomes, polysomes, intermediate filaments, and mitochondria were observed in
      stratum spinosum at all the phases of the oestrus cycle. At MM, LM/ED, and MD,
      the stratum spinosum had numerous desmosomes with tonofilaments, large microvilli
      that intermingled at the intercellular spaces and evidence of trapped/migrating
      neutrophils and lymphocytes. The superficial layer displayed short microvilli at
      mid-proestrus, cornification at LP/EE and desquamation at ME while it showed
      condensation of intermediate filaments; projections of large microvilli into the
      luminal surface at MM, and embeddement of neutrophils at LM/ED as well as MD.
      This study looked into the reproductive biology of female African giant rats to
      produce baseline information on its reproductive organs and represented the first
      comprehensive description of the vagina at the ultrastructural level during
      oestrous cycle.

PMID- 24737724
TI  - Respiration phase-locks to fast stimulus presentations: implications for the
      interpretation of posterior midline "deactivations".
AB  - The posterior midline region (PMR)-considered a core of the default mode network
      is deactivated during successful performance in different cognitive tasks. The
      extent of PMR-deactivations is correlated with task-demands and associated with
      successful performance in various cognitive domains. In the domain of episodic
      memory, functional MRI (fMRI) studies found that PMR-deactivations reliably
      predict learning (successful encoding). Yet it is unclear what explains this
      relation. One intriguing possibility is that PMR-deactivations are partially
      mediated by respiratory artifacts. There is evidence that the fMRI signal in PMR
      is particularly prone to respiratory artifacts, because of its large surrounding
      blood vessels. As respiratory fluctuations have been shown to track changes in
      attention, it is critical for the general interpretation of fMRI results to
      clarify the relation between respiratory fluctuations, cognitive performance, and
      fMRI signal. Here, we investigated this issue by measuring respiration during
      word encoding, together with a breath-holding condition during fMRI-scanning.
      Stimulus-locked respiratory analyses showed that respiratory fluctuations
      predicted successful encoding via a respiratory phase-locking mechanism. At the
      same time, the fMRI analyses showed that PMR-deactivations associated with
      learning were reduced during breath-holding and correlated with individual
      differences in the respiratory phase-locking effect during normal breathing. A
      left frontal region--used as a control region--did not show these effects. These
      findings indicate that respiration is a critical factor in explaining the link
      between PMR-deactivation and successful cognitive performance. Further research
      is necessary to demonstrate whether our findings are restricted to episodic
      memory encoding, or also extend to other cognitive domains.

PMID- 24737726
TI  - NMR fingerprints of the drug-like natural-product space identify iotrochotazine
      A: a chemical probe to study Parkinson's disease.
AB  - The NMR spectrum of a mixture of small molecules is a fingerprint of all of its
      components. Herein, we present an NMR fingerprint method that takes advantage of
      the fact that fractions contain simplified NMR profiles, with minimal signal
      overlap, to allow the identification of unique spectral patterns. The approach is
      exemplified in the identification of a novel natural product, iotrochotazine A
      (1), sourced from an Australian marine sponge Iotrochota sp. Compound 1 was used
      as a chemical probe in a phenotypic assay panel based on human olfactory
      neurosphere-derived cells (hONS) from idiopathic Parkinson's disease patients.
      Compound 1 at 1 MUM was not cytotoxic but specifically affected the morphology
      and cellular distribution of lysosomes and early endosomes.

PMID- 24737727
TI  - Pupylated proteins in Corynebacterium glutamicum revealed by MudPIT analysis.
AB  - In a manner similar to ubiquitin, the prokaryotic ubiquitin-like protein (Pup)
      has been shown to target proteins for degradation via the proteasome in
      mycobacteria. However, not all actinobacteria possessing the Pup protein also
      contain a proteasome. In this study, we set out to study pupylation in the
      proteasome-lacking non-pathogenic model organism Corynebacterium glutamicum. A
      defined pup deletion mutant of C. glutamicum ATCC 13032 grew aerobically as the
      parent strain in standard glucose minimal medium, indicating that pupylation is
      dispensable under these conditions. After expression of a Pup derivative carrying
      an aminoterminal polyhistidine tag in the Deltapup mutant and Ni(2+)-chelate
      affinity chromatography, pupylated proteins were isolated. Multidimensional
      protein identification technology (MudPIT) and MALDI-TOF-MS/MS of the elution
      fraction unraveled 55 proteins being pupylated in C. glutamicum and 66 pupylation
      sites. Similar to mycobacteria, the majority of pupylated proteins are involved
      in metabolism or translation. Our results define the first pupylome of an
      actinobacterial species lacking a proteasome, confirming that other fates besides
      proteasomal degradation are possible for pupylated proteins.

PMID- 24737728
TI  - Respiratory source control using surgical masks with nanofiber media.
AB  - BACKGROUND: Potentially infected individuals ('source') are sometimes encouraged
      to use face masks to reduce exposure of their infectious aerosols to others
      ('receiver'). To improve compliance with Respiratory Source Control via face mask
      and therefore reduce receiver exposure, a mask should be comfortable and
      effective. We tested a novel face mask designed to improve breathability and
      filtration using nanofiber filtration. METHODS: Using radiolabeled test aerosols
      and a calibrated exposure chamber simulating source to receiver interaction,
      facepiece function was measured with a life-like ventilated manikin model.
      Measurements included mask airflow resistance (pressure difference during
      breathing), filtration, (mask capture of exhaled radiolabeled test aerosols), and
      exposure (the transfer of 'infectious' aerosols from the 'source' to a
      'receiver'). Polydisperse aerosols were measured at the source with a mass median
      aerodynamic diameter of 0.95 um. Approximately 90% of the particles were <2.0 um.
      Tested facepieces included nanofiber prototype surgical masks, conventional
      surgical masks, and for comparison, an N95-class filtering facepiece respirator
      (commonly known as an 'N95 respirator'). Airflow through and around conventional
      surgical face mask and nanofiber prototype face mask was visualized using
      Schlieren optical imaging. RESULTS: Airflow resistance [DeltaP, cmH2O] across
      sealed surgical masks (means: 0.1865 and 0.1791 cmH2O) approached that of the N95
      (mean: 0.2664 cmH2O). The airflow resistance across the nanofiber face mask
      whether sealed or not sealed (0.0504 and 0.0311 cmH2O) was significantly reduced
      in comparison. In addition, 'infected' source airflow filtration and receiver
      exposure levels for nanofiber face masks placed on the source were comparable to
      that achieved with N95 placed on the source; 98.98% versus 82.68% and 0.0194
      versus 0.0557, respectively. Compared to deflection within and around the
      conventional face masks, Schlieren optical imaging demonstrated enhanced airflow
      through the nanofiber mask. CONCLUSIONS: Substituting nanofiber for conventional
      filter media significantly reduced face mask airflow resistance directing more
      airflow through the face mask resulting in enhanced filtration. Respiratory
      source control efficacy similar to that achieved through the use of an N95
      respirator worn by the source and decreased airflow resistance using nanofiber
      masks may improve compliance and reduce receiver exposure.

PMID- 24737729
TI  - Collagen-lactoferrin fibrillar coatings enhance osteoblast proliferation and
      differentiation.
AB  - Lactoferrin is a milk-derived glycoprotein with anabolic effects on the bone
      tissue. In this study, artificial extracellular matrices (aECM) consisting of
      collagen type I fibrils formed in the presence of lactoferrin at two different
      concentrations (0.5 and 1 mg mL(-1) ) were prepared on the surface of poly(lactic
      co-glycolic acid) (PLGA) foils. The aim of the study was to investigate the
      effects of aECM on the adhesion, growth and osteogenic differentiation of human
      osteoblast-like Saos-2 cells. On days 1 and 3 after seeding, higher numbers of
      cells were found on samples with collagen and collagen-lactoferrin coatings
      (particularly on those formed at the higher concentration of lacroferrin) than on
      control microscopic glass coverslips. Cells on coatings formed in the presence of
      lactoferrin had more numerous and better developed vinculin-containing focal
      adhesion plaques. On day 7, cells on coatings with and without lactoferrin
      produced significantly higher levels of osteocalcin than cells on control
      polystyrene cell culture dishes, the highest average values being found on
      samples with the lower concentration of lactoferrin. Expression of collagen I and
      alkaline phosphatase was on a similar level in cells on all tested samples and
      control polystyrene. Thus, lactoferrin promotes adhesion, growth and osteogenic
      differentiation of Saos-2 cells and is promising as a bone implant coating
      component.

PMID- 24737730
TI  - Variation in timing, duration, intensity, and direction of adolescent growth in
      the mandible, maxilla, and cranial base: the Fels longitudinal study.
AB  - There is considerable individual variation in the timing, duration, and intensity
      of growth that occurs in the craniofacial complex during childhood and
      adolescence. The purpose of this article is to describe the extent of this
      variation between traits and between individuals within the Fels Longitudinal
      Study (FLS). Polynomial multilevel models were used to estimate the ages of
      onset, peak velocity, and cessation of adolescent growth, the time between these
      ages, the amount of growth between these ages, and peak velocity. This was done
      at both the group and individual levels for standard cephalometric measurements
      of the lengths of the mandible, maxilla, and cranial base, the gonial angle, and
      the saddle angle. Data are from 293 untreated boys and girls age 4-24 years in
      the FLS. The timing of the adolescent growth spurt was, in general, not
      significantly different between the mandible and the maxilla, with each having an
      earlier age of onset, later age of peak velocity, and later age of cessation of
      growth as compared to the cranial base length. Compared to lengths, angles had in
      general later ages of onset, peak velocity, and cessation of growth. Accurate
      characterization of the ontogenetic trajectories of the traits in the
      craniofacial complex is critical for both clinicians seeking to optimize
      treatment timing and anatomists interested in examining heterochrony.

PMID- 24737731
TI  - Why have so few proteomic biomarkers "survived" validation? (Sample size and
      independent validation considerations).
AB  - Proteomic biomarker discovery has led to the identification of numerous potential
      candidates for disease diagnosis, prognosis, and prediction of response to
      therapy. However, very few of these identified candidate biomarkers reach
      clinical validation and go on to be routinely used in clinical practice. One
      particular issue with biomarker discovery is the identification of significantly
      changing proteins in the initial discovery experiment that do not validate when
      subsequently tested on separate patient sample cohorts. Here, we seek to
      highlight some of the statistical challenges surrounding the analysis of LC-MS
      proteomic data for biomarker candidate discovery. We show that common statistical
      algorithms run on data with low sample sizes can overfit and yield misleading
      misclassification rates and AUC values. A common solution to this problem is to
      prefilter variables (via, e.g. ANOVA and or use of correction methods such as
      Bonferonni or false discovery rate) to give a smaller dataset and reduce the size
      of the apparent statistical challenge. However, we show that this exacerbates the
      problem yielding even higher performance metrics while reducing the predictive
      accuracy of the biomarker panel. To illustrate some of these limitations, we have
      run simulation analyses with known biomarkers. For our chosen algorithm (random
      forests), we show that the above problems are substantially reduced if a
      sufficient number of samples are analyzed and the data are not prefiltered. Our
      view is that LC-MS proteomic biomarker discovery data should be analyzed without
      prefiltering and that increasing the sample size in biomarker discovery
      experiments should be a very high priority. 

PMID- 24737732
TI  - Structural basis of furan-amino acid recognition by a polyspecific aminoacyl-tRNA
      synthetase and its genetic encoding in human cells.
AB  - The site-selective introduction of photo-crosslinking groups into proteins
      enables the discovery and mapping of weak and/or transient protein interactions
      with high spatiotemporal resolution, both in vitro and in vivo. We report the
      genetic encoding of a furan-based, photo-crosslinking amino acid in human cells;
      it can be activated with red light, thus offering high penetration depths in
      biological samples. This is achieved by activation of the amino acid and charging
      to its cognate tRNA by a pyrrolysyl-tRNA-synthetase (PylRS) mutant with broad
      polyspecificity. To gain insights into the recognition of this amino acid and to
      provide a rationale for its polyspecificity, we solved three crystal structures
      of the PylRS mutant: in its apo-form, in complex with adenosine 5'-(beta,gamma
      imido)triphosphate (AMP-PNP) and in complex with the AMP ester of the furan amino
      acid. These structures provide clues for the observed polyspecificity and
      represent a promising starting point for the engineering of PylRS mutants with
      further increased substrate scope. 

PMID- 24737734
TI  - Protective effect of truncated Na+/K+-ATPase beta on ischemia/reperfusion-induced
      renal injury in rats.
AB  - Renal ischemia/reperfusion(I/R) is an important injury part of ischemic acute
      renal failure, and it is also the main factor that affects the early functional
      recovery and the long-term survival of transplanted kidney in renal
      transplantation. In this study, we cloned and expressed truncated Na+/K+-ATPase
      beta(tNKAbeta) and demonstrated that tNKAbeta could activate NKA alpha subunit
      and induce protective effect on human kidney-2(HK-2) cells via PKCE signal
      pathway. The half maximum effective concentrations (EC50) of tNKAbeta were 0.24
      uM. Furthermore, the application of EAVSLKPT (PKCE inhibitor) could abolish the
      protective effect of tNKAbeta in HK-2 cells subjected to ischemia/reperfusion. To
      identify the protective effect of tNKAbeta against the I/R injury in the kidney,
      Sprague-Dawley rats were treated with tNKAbeta (75 mg/kg) for 2 h before
      ischemia. The tNKAbeta-treated group demonstrated a significant improvement in
      renal function with a lower serum creatinine and blood urea nitrogen (BUN) levels
      on postoperative days 1-6. Renal sections obtained from rats of the I/R group
      showed serious renal injury which included degeneration of tubular structure,
      tubular dilation, swelling and necrosis, luminal congestion, and muddy brown
      casts formed by sloughing of severely damaged tubular epithelial cells. However,
      sections of rats that were administered with tNKAbeta 2 h before reperfusion
      showed marked reduction of the histological features of renal injury compared
      with kidneys that were subjected to I/R only. In conclusion, the protective
      effects of tNKAbeta against renal I/R injury have been evaluated for the first
      time, and these protective effects may occur via stimulation of PKCE pathways.

PMID- 24737733
TI  - Cancer stem cell-specific scavenger receptor CD36 drives glioblastoma
      progression.
AB  - Glioblastoma (GBM) contains a self-renewing, tumorigenic cancer stem cell (CSC)
      population which contributes to tumor propagation and therapeutic resistance.
      While the tumor microenvironment is essential to CSC self-renewal, the mechanisms
      by which CSCs sense and respond to microenvironmental conditions are poorly
      understood. Scavenger receptors are a broad class of membrane receptors well
      characterized on immune cells and instrumental in sensing apoptotic cellular
      debris and modified lipids. Here, we provide evidence that CSCs selectively use
      the scavenger receptor CD36 to promote their maintenance using patient-derived
      CSCs and in vivo xenograft models. CD36 expression was observed in GBM cells in
      addition to previously described cell types including endothelial cells,
      macrophages, and microglia. CD36 was enriched in CSCs and was able to
      functionally distinguish self-renewing cells. CD36 was coexpressed with integrin
      alpha 6 and CD133, previously described CSC markers, and CD36 reduction resulted
      in concomitant loss of integrin alpha 6 expression, self-renewal, and tumor
      initiation capacity. We confirmed oxidized phospholipids, ligands of CD36, were
      present in GBM and found that the proliferation of CSCs, but not non-CSCs,
      increased with exposure to oxidized low-density lipoprotein. CD36 was an
      informative biomarker of malignancy and negatively correlated to patient
      prognosis. These results provide a paradigm for CSCs to thrive by the selective
      enhanced expression of scavenger receptors, providing survival, and metabolic
      advantages.

PMID- 24737735
TI  - Microscale technologies for regulating human stem cell differentiation.
AB  - During development and regeneration, tissues emerge from coordinated sequences of
      stem cell renewal, specialization, and assembly that are orchestrated by cascades
      of regulatory factors. This complex in vivo milieu, while necessary to fully
      recapitulate biology and to properly engineer progenitor cells, is difficult to
      replicate in vitro. We are just starting to fully realize the importance of the
      entire context of cell microenvironment-the other cells, three-dimensional
      matrix, molecular and physical signals. Bioengineered environments that combine
      tissue-specific transport and signaling are critical to study cellular responses
      at biologically relevant scales and in settings predictive of human condition. We
      therefore developed microbioreactors that couple the application of fast dynamic
      changes in environmental signals with versatile, high-throughput operation and
      imaging capability. Our base device is a microfluidic platform with an array of
      microwells containing cells or tissue constructs that are exposed to stable
      concentration gradients. Mathematical modeling of flow and mass transport can
      predict the shape of these gradients and the kinetic changes in local
      concentrations. A single platform, the size of a microscope slide, contains up to
      120 biological samples. As an example of application, we describe studies of cell
      fate specification and mesodermal lineage commitment in human embryonic stem
      cells and induced pluripotent stem cells. The embryoid bodies formed from these
      cells were subjected to single and multiple concentration gradients of Wnt3a,
      Activin A, bone morphogenic protein 4 (BMP4), and their inhibitors, and the gene
      expression profiles were correlated to the concentration gradients of morphogens
      to identify the exact conditions for mesodermal differentiation.

PMID- 24737737
TI  - Cyclosporine A protects podocytes via stabilization of cofilin-1 expression in
      the unphosphorylated state.
AB  - Podocyte foot process (FP) is dysregulated in nephrotic syndrome. The effacement
      of podocyte FPs typically arises following perturbations in the actin
      cytoskeleton. Recent data suggest that the effects of calcineurin (CaN) inhibitor
      cyclosporine A (CsA) are independent of its effects on T-cells, and CsA has been
      identified as stabilizing the actin cytoskeleton through stabilizing synaptopodin
      in podocytes, and thereby directly reducing proteinuria. Other studies showed
      that CsA could regulate cofilin-1 directly within tubular epithelial cells.
      However, whether synaptopodin is the only target of CsA or whether the
      antiproteinuric role of CsA is played by regulating cofilin-1 in podocytes has
      not been studied. In the present study, changes in the expression and
      distribution of nephrin, synaptopodin, cofilin-1 and phosphorylated cofilin-1
      (pho-cofilin-1) were detected in both puromycin aminonucleoside (PAN) induced
      nephrotic rats treated with CsA and cultured podocytes exposed to PAN
      with/without CsA. Cofilin-1, synaptopodin mRNA was knocked down or combined by
      siRNA to investigate whether cofilin-1 was critical for the protective effect of
      CsA and whether the effect of CsA on cofilin-1 was independent of its effect on
      synaptopodin. We found that CsA reduced proteinuria and repaired FP effacement of
      PAN-induced nephropathy, restored expression of nephrin, synaptopodin, cofilin-1,
      pho-cofilin-1 both in vivo and in vitro. CsA also repaired actin cytoskeleton
      impaired by PAN in vitro. The protective effect of CsA was diminished when
      cofilin-1 was knocked down compared to negative control. Synaptopodin knocked
      down had no effect on cofilin-1. The protective effect of CsA decreased
      significantly when cofilin-1 and synaptopodin were simultaneously knocked down
      compared to only cofilin-1 knock down. In conclusion, the antiproteinuric effect
      of CsA is derived from the stabilization of the podocyte actin cytoskeleton by
      upregulating expression of cofilin-1, which was independent of its effect on
      synaptopodin.

PMID- 24737738
TI  - Distinct karyotypes in two offspring of a man with jumping translocation
      karyotype 45,XY,der(16)t(16;22)(q24;q11.2), -22
      [59]/45,XY,der(1)t(1;22)(p36;q11.2), -22 [11]/45,XY,der(22)t(22;22)(p13;q11.2), 
      22 [10].
AB  - We examined a man and his daughter, who both had different jumping translocation
      karyotypes. The man's wife was pregnant and had been referred for prenatal
      diagnosis of the fetus. The karyotype of the husband's peripheral blood
      lymphocytes was 45,XY,der(16)t(16;22)(q24;q11.2), -22
      [59]/45,XY,der(1)t(1;22)(p36;q11.2), -22 [11]/45,XY,der(22)t(22;22)(p13;q11.2), 
      22 [10]. The karyotype of the daughter's peripheral blood lymphocytes was
      45,XX,der(16)t(16;22)(q24;q11.2), -22 [45]/45,XX,der(9)t(9;22)(q34;q11.2), -22
      [30]/45,XX,der(5)t(5;22)(q35;q11.2), -22 [25]. The wife and the fetus both had a
      normal karyotype. To the best of our knowledge, the present familial transmitted
      jumping translocation has not been previously described and the jumping
      translocation in the husband and daughter did not cause any phenotypic
      abnormalities.

PMID- 24737739
TI  - The evaluation of vertebrobasilar artery system in neuro-Behcet and Behcet
      disease using magnetic resonance angiography.
AB  - The aim of this study is the evaluation of the vertebrobasilar artery system in
      patients with Behcet's and Neuro-Behcet's disease. For this aim; 20 adults with
      clinically diagnosed Behcet's disease, 20 adults with Neuro-Behcet's disease, and
      19 age- and gender-matched controls were examined by magnetic resonance
      angiography (MRA). During MRA, diameters of left vertebral artery (LVA), right
      vertebral artery (RVA), basilar artery (BA), and proximal segment (P1) of
      posterior cerebral artery between origin and junction with the posterior
      communicating artery were measured. In all groups, LVA was dominant than RVA (P <
      0.05). The diameters of BA and right P1 of Neuro-Behcet's disease were larger
      than the other groups (P < 0.05). In addition, the diameters of left P1 of Neuro
      Behcet's disease were larger but not statistically significant. There is no
      difference between the groups in terms of gender. Behcet's disease can affect
      vascular structures; therefore vertebrobasilar artery system should be examined
      in patients with Behcet's and Neuro-Behcet's disease.

PMID- 24737736
TI  - Microphysiological modeling of the reproductive tract: a fertile endeavor.
AB  - Preclinical toxicity testing in animal models is a cornerstone of the drug
      development process, yet it is often unable to predict adverse effects and
      tolerability issues in human subjects. Species-specific responses to
      investigational drugs have led researchers to utilize human tissues and cells to
      better estimate human toxicity. Unfortunately, human cell-derived models are
      imperfect because toxicity is assessed in isolation, removed from the normal
      physiologic microenvironment. Microphysiological modeling often referred to as
      'organ-on-a-chip' or 'human-on-a-chip' places human tissue into a microfluidic
      system that mimics the complexity of human in vivo physiology, thereby allowing
      for toxicity testing on several cell types, tissues, and organs within a more
      biologically relevant environment. Here we describe important concepts when
      developing a repro-on-a-chip model. The development of female and male
      reproductive microfluidic systems is critical to sex-based in vitro toxicity and
      drug testing. This review addresses the biological and physiological aspects of
      the male and female reproductive systems in vivo and what should be considered
      when designing a microphysiological human-on-a-chip model. Additionally,
      interactions between the reproductive tract and other systems are explored,
      focusing on the impact of factors and hormones produced by the reproductive tract
      and disease pathophysiology.

PMID- 24737740
TI  - Unraveling the specificities of the different human methionine sulfoxide
      reductases.
AB  - The oxidation of free and protein-bound methionine into methionine sulfoxide is a
      frequently occurring modification caused by ROS. Most organisms express
      methionine sulfoxide reductases (MSR enzymes) to repair this potentially damaging
      modification. Humans express three different MSRB enzymes which reside in
      different cellular compartments. In this study, we have explored the specificity
      of the human MSRB enzymes both by in silico modeling and by experiments on
      oxidized peptides. We found that MSRB1 is the least specific MSRB enzyme, which
      is in agreement with the observation that MSRB1 is the only MSRB enzyme found in
      the cytosol and the nucleus, and therefore requires a broad specificity to reduce
      all possible substrates. MSRB2 and MSRB3, which are both found in mitochondria,
      are more specific but because of their co-occurrence they can likely repair all
      possible substrates.

PMID- 24737741
TI  - Quinquephenyl: the simplest rigid-rod-like nematic liquid crystal, or is it? An
      atomistic simulation.
AB  - We have performed an atomistic molecular-dynamics study on the molecular
      organization and liquid-crystalline properties of quinquephenyl (P5), a
      prototypical mesogen that is of interest for organic electronics. The
      thermotropic behavior reveals different mesophases. When cooling down from the
      isotropic phase, a transition to nematic (~715 K) is found, then a smectic SA
      (~657 K) and another smectic, SXA (~642 K), before a crystalline phase is
      recovered (~617 K). This phase sequence is compared with experimental findings.
      The different phases are described in terms of their molecular organization,
      orientational and positional order parameters, and pair distribution functions,
      as well as of their dynamics properties. In particular, the smectic phases that
      have not yet been characterized experimentally are discussed. By analyzing the
      effective shape of P5, it is concluded that its internal torsions and bending
      make it less rigid than could be expected.

PMID- 24737742
TI  - Evidence for increased SOX3 dosage as a risk factor for X-linked hypopituitarism
      and neural tube defects.
AB  - Genomic duplications of varying lengths at Xq26-q27 involving SOX3 have been
      described in families with X-linked hypopituitarism. Using array-CGH we detected
      a 1.1 Mb microduplication at Xq27 in a large family with three males suffering
      from X-linked hypopituitarism. The duplication was mapped from 138.7 to 139.8 Mb,
      harboring only two annotated genes, SOX3 and ATP11C, and was shown to be a direct
      tandem copy number gain. Unexpectedly, the microduplication did not fully
      segregate with the disease in this family suggesting that SOX3 duplications have
      variable penetrance for X-linked hypopituitarism. In the same family, a female
      fetus presenting with a neural tube defect was also shown to carry the SOX3 copy
      number gain. Since we also demonstrated increased SOX3 mRNA levels in amnion
      cells derived from an unrelated t(X;22)(q27;q11) female fetus with spina bifida,
      we propose that increased levels of SOX3 could be a risk factor for neural tube
      defects.

PMID- 24737746
TI  - Study of carbamate-modified disiloxane in porous PVDF-HFP membranes: new
      electrolytes/separators for lithium-ion batteries.
AB  - A gel electrolyte membrane is obtained through the absorption of a carbamate
      modified liquid disiloxane-containing lithium bis(trifluoromethane)sulfonimide
      (LiTFSI) by using macroporous poly(vinylidene fluoride-hexafluoropropylene) (PVDF
      HFP) membranes. The porous membranes are prepared by means of a phase inversion
      technique. The resulting gel electrolyte membrane is studied by using
      differential scanning calorimetry, Fourier-transform infrared (FTIR)
      spectroscopy, and microscope mapping through coherent anti-Stokes Raman
      scattering (CARS) confocal microscopy and impedance spectroscopy. The ionic
      conductivity of the gel electrolyte is 10(-4) S cm(-1) at 20  degrees C. FTIR
      spectroscopy reveals interactions between LiTFSI and the carbonyl moiety of the
      disiloxane. No interactions between LiTFSI and PVDF-HFP or between disiloxane and
      PVDF-HFP are detected by FTIR spectroscopy. Furthermore, the distribution of the
      alpha and beta/gamma phases of PVDF-HFP and the homogeneous distribution of
      disiloxane/LiTFSI in the gel electrolyte membranes are examined by FTIR mapping.
      CARS confocal microscopy is used to image the three-dimensional
      interconnectivity, which reveals a reticulated structure of macrovoids in the
      porous PVDF-HFP framework. Owing to properties such as electrochemical and
      thermal stability of the disiloxane-based liquid electrolyte and the mechanical
      stability of the porous PVDF-HFP membrane, the gel electrolyte membranes
      presented herein are promising candidates for applications as
      electrolytes/separators in lithium-ion batteries. 

PMID- 24737743
TI  - The association between social cognition and executive functioning and symptoms
      of anxiety and depression in adolescents with autism spectrum disorders.
AB  - While high levels of anxiety and depression are now recognized as major co
      occurring problems in children and young people with an autism spectrum disorder
      (ASD), research examining possible associations with individual differences in
      neurocognitive functioning has been limited. This study included 90 adolescents
      with an ASD aged 14-16 years with a full-scale IQ > 50. Using structural equation
      modeling, we examined the independent relationships between multiple measures of
      executive functioning and social cognition on severity of anxiety or depressive
      symptoms. Results indicated a significant association between poorer executive
      functioning and higher levels of anxiety, but not depression. In contrast, social
      cognition ability was not associated with either anxiety or depression. This
      study is the first to report significant associations between executive functions
      and anxiety in ASD. This may suggest that poor executive functioning is one
      factor associated with the high prevalence of anxiety disorder in children and
      adolescents with ASD.

PMID- 24737747
TI  - Excess alpha-tocopherol decreases extrahepatic phylloquinone in phylloquinone-fed
      rats but not menaquinone-4 in menaquinone-4-fed rats.
AB  - SCOPE: The effects of vitamin E on vitamin K metabolism were elucidated by
      comparing the effect of tocopherol intake on vitamin K concentrations in rats fed
      phylloquinone (PK) or menaquinone (MK)-4. METHODS AND RESULTS: Initially, the
      dietary effect of RRR-alpha-tocopherol, but not RRR-gamma-tocopherol, in
      decreasing extrahepatic PK concentrations was confirmed. Subsequently, rats were
      fed a PK or MK-4-containing diet (0.75 mg/kg) with RRR-alpha-tocopherol (0, 10,
      50, or 500 mg/kg) for 6 weeks. In rats fed PK, alpha-tocopherol consumption
      decreased PK in kidney, lung, heart, muscle, testis, and brain but not in serum
      and liver. However, in rats fed MK-4, alpha-tocopherol consumption did not
      decrease MK-4 in serum and tissues. Finally, vitamin K- and E-depleted rats were
      administered PK or MK-4 (0.2 mg) with RRR-alpha-tocopherol (0, 1, or 10 mg) by
      gavage. After PK administration, alpha-tocopherol was observed to decrease PK in
      kidney, adrenal gland, lung, testis, and brain but not in serum and liver,
      whereas, after MK-4 administration, alpha-tocopherol did not affect MK-4 in serum
      and tissues. CONCLUSION: Excess alpha-tocopherol decreased extrahepatic PK in
      rats fed PK but not MK-4 in rats fed MK-4.

PMID- 24737749
TI  - Sodium-ion battery based on an electrochemically converted NaFePO4 cathode and
      nanostructured tin-carbon anode.
AB  - We report a new sodium-ion battery formed by coupling a NaFePO(4) cathode and a
      nanocomposite tin-carbon (Sn-C) sodium-alloying anode. The NaFePO(4) cathode is
      obtained by Li-Na conversion of a LiFePO(4) cathode directly in the full cell
      employing the Sn-C anode and a sodium-ion electrolyte. The results show that the
      unique approach adopted here is capable of successfully and efficiently
      converting LiFePO(4) into NaFePO(4) in a sodium-ion battery operating at a
      voltage of 3 V, with a maximum reversible capacity of 150 mAh g(-1), high
      reversibility, and high rate capability.

PMID- 24737750
TI  - Magnetic nanoparticles to recover cellular organelles and study the time resolved
      nanoparticle-cell interactome throughout uptake.
AB  - Nanoparticles in contact with cells and living organisms generate quite novel
      interactions at the interface between the nanoparticle surface and the
      surrounding biological environment. However, a detailed time resolved molecular
      level description of the evolving interactions as nanoparticles are internalized
      and trafficked within the cellular environment is still missing and will
      certainly be required for the emerging arena of nanoparticle-cell interactions to
      mature. In this paper promising methodologies to map out the time resolved
      nanoparticle-cell interactome for nanoparticle uptake are discussed. Thus silica
      coated magnetite nanoparticles are presented to cells and their magnetic
      properties used to isolate, in a time resolved manner, the organelles containing
      the nanoparticles. Characterization of the recovered fractions shows that
      different cell compartments are isolated at different times, in agreement with
      imaging results on nanoparticle intracellular location. Subsequently the
      internalized nanoparticles can be further isolated from the recovered organelles,
      allowing the study of the most tightly nanoparticle-bound biomolecules, analogous
      to the 'hard corona' that so far has mostly been characterized in extracellular
      environments. Preliminary data on the recovered nanoparticles suggest that
      significant portion of the original corona (derived from the serum in which
      particles are presented to the cells) is preserved as nanoparticles are
      trafficked through the cells. 

PMID- 24737751
TI  - mRNA degradation: an underestimated factor in steady-state transcript levels of
      cytochrome c oxidase subunits?
AB  - Steady-state mRNA levels are determined by synthesis and degradation; however,
      changes in mRNA levels are usually attributed to transcription. For cytochrome c
      oxidase (COX), cold acclimation typically leads to an increase in COX activity
      while transcript levels for the nuclear-encoded subunits change non
      stoichiometrically. Whether those patterns are caused by differences in subunit
      transcription rates, decay rates or both was not known. We assessed decay rates
      of transcripts for COX subunits, including representatives that decreased,
      increased in parallel with COX or increased in excess of COX. Low temperature
      reduced the decay rate of all transcripts; however, COX subunits displayed higher
      thermal sensitivity than housekeeping genes. The lower decay rates for COX
      transcripts might explain some of their increase in response to cold acclimation.
      The reason for the exaggerated transcript response of two subunits (COX6B-1 and
      COX7A-2) may be due to decreased decay. However, decay rate differences could not
      explain the patterns seen with another subunit that did not change in mRNA level
      with thermal acclimation (COX6A-2). Further, the decay patterns differed between
      two thermal acclimation experiments, which may explain some of the heterogeneity
      seen in fish studies. The differences in decay rates suggest that the lack of
      stoichiometry in mRNA levels is exacerbated by post-transcriptional mechanisms.
      Collectively, these results suggest that temperature-induced differences in COX
      subunit mRNA levels and deviations from stoichiometry between them may partially
      arise from subunit-specific sensitivities to degradation. We suggest that all
      subunits are controlled by transcription, and that exaggerated responses of some
      subunits are due to reduced decay rates. 

PMID- 24737748
TI  - Identification of susceptibility loci for colorectal cancer in a genome-wide meta
      analysis.
AB  - To identify common variants influencing colorectal cancer (CRC) risk, we
      performed a meta-analysis of five genome-wide association studies, comprising
      5626 cases and 7817 controls of European descent. We conducted replication of top
      ranked single nucleotide polymorphisms (SNPs) in additional series totalling 14
      037 cases and 15 937 controls, identifying a new CRC risk locus at 10q24.2
      [rs1035209; odds ratio (OR) = 1.13, P = 4.54 * 10(-11)]. We also performed meta
      analysis of our studies, with previously published data, of several recently
      purported CRC risk loci. We failed to find convincing evidence for a previously
      reported genome-wide association at rs11903757 (2q32.3). Of the three additional
      loci for which evidence of an association in Europeans has been previously
      described we failed to show an association between rs59336 (12q24.21) and CRC
      risk. However, for the other two SNPs, our analyses demonstrated new, formally
      significant associations with CRC. These are rs3217810 intronic in CCND2
      (12p13.32; OR = 1.19, P = 2.16 * 10(-10)) and rs10911251 near LAMC1 (1q25.3; OR =
      1.09, P = 1.75 * 10(-8)). Additionally, we found some evidence to support a
      relationship between, rs647161, rs2423297 and rs10774214 and CRC risk originally
      identified in East Asians in our European datasets. Our findings provide further
      insights into the genetic and biological basis of inherited genetic
      susceptibility to CRC. 

PMID- 24737752
TI  - Intraspecific scaling of arterial blood pressure in the Burmese python.
AB  - Interspecific allometric analyses indicate that mean arterial blood pressure
      (MAP) increases with body mass of snakes and mammals. In snakes, MAP increases in
      proportion to the increased distance between the heart and the head, when the
      heart-head vertical distance is expressed as rhogh (where rho is the density of
      blood, G: is acceleration due to gravity and h is the vertical distance above the
      heart), and the rise in MAP is associated with a larger heart to normalize wall
      stress in the ventricular wall. Based on measurements of MAP in Burmese pythons
      ranging from 0.9 to 3.7 m in length (0.20-27 kg), we demonstrate that although
      MAP increases with body mass, the rise in MAP is merely half of that predicted by
      heart-head distance. Scaling relationships within individual species, therefore,
      may not be accurately predicted by existing interspecific analyses. 

PMID- 24737753
TI  - Oxygen diffusion limitation triggers ventilatory movements during spiracle
      closure when insects breathe discontinuously.
AB  - During discontinuous gas exchange cycles in insects, spiracular opening follows a
      typical prolonged period of spiracle closure. Gas exchange with the environment
      occurs mostly during the period of full spiracular opening. In this study we
      tested the hypothesis that recently reported ventilatory movements during the
      spiracle closure period serve to mix the tracheal system gaseous contents, and
      support diffusive exchanges with the tissues. Using heliox (21% O2, 79% He), we
      found that by increasing oxygen diffusivity in the gas phase, ventilatory
      movements of Schistocerca gregaria were significantly delayed compared with
      normoxic conditions. Exposure to hyperoxic conditions (40% O2, 60% N2) resulted
      in a similar delay in forced ventilation. Together, these results indicate that
      limits to oxygen diffusion to the tissues during spiracle closure trigger
      ventilatory movements, which in turn support tissue demands. These findings
      contribute to our understanding of the mechanistic basis of respiratory gas
      exchange between insect tissues and the environment. 

PMID- 24737754
TI  - Control of moth flight posture is mediated by wing mechanosensory feedback.
AB  - Flying insects rapidly stabilize after perturbations using both visual and
      mechanosensory inputs for active control. Insect halteres are mechanosensory
      organs that encode inertial forces to aid rapid course correction during flight
      but serve no aerodynamic role and are specific to two orders of insects (Diptera
      and Strepsiptera). Aside from the literature on halteres and recent work on the
      antennae of the hawkmoth Manduca sexta, it is unclear how other flying insects
      use mechanosensory information to control body dynamics. The mechanosensory
      structures found on the halteres, campaniform sensilla, are also present on
      wings, suggesting that the wings can encode information about flight dynamics. We
      show that the neurons innervating these sensilla on the forewings of M. sexta
      exhibit spike-timing precision comparable to that seen in previous reports of
      campaniform sensilla, including haltere neurons. In addition, by attaching
      magnets to the wings of moths and subjecting these animals to a simulated pitch
      stimulus via a rotating magnetic field during tethered flight, we elicited the
      same vertical abdominal flexion reflex these animals exhibit in response to
      visual or inertial pitch stimuli. Our results indicate that, in addition to their
      role as actuators during locomotion, insect wings serve as sensors that initiate
      reflexes that control body dynamics. 

PMID- 24737755
TI  - Defensive slime formation in Pacific hagfish requires Ca2+- and aquaporin
      mediated swelling of released mucin vesicles.
AB  - Hagfishes defend themselves from fish predators via the rapid deployment of a
      fibrous slime that adheres to and clogs gills. The slime transforms from a thick
      glandular exudate to a fully hydrated product in a fraction of a second through a
      process that involves the swelling and rupture of numerous mucin vesicles. Here
      we demonstrate that the vesicle membrane plays an important role in regulating
      the swelling of mucin granules, and provide evidence that the membrane contains
      proteins that facilitate the movement of ions and water molecules. By exposing
      isolated mucin vesicles to varying combinations of inorganic ions, organic
      compounds and membrane channel inhibitors, we found that the majority of hagfish
      mucin vesicles require Ca(2+) to rupture. We also show that Ca(2+)-dependent
      rupture can be pharmacologically inhibited, which suggests a role for Ca(2+)
      activated membrane transporters. We demonstrate that the aquaporin inhibitor
      mercuric chloride reduces the rate of vesicle swelling by an order of magnitude,
      which suggests that aquaporins facilitate the influx of water during vesicle
      deployment. Molecular evidence of two aquaporin homologues expressed in the slime
      glands further supports this idea. We propose a model of hagfish slime mucin
      vesicle rupture that involves Ca(2+)-activated transporters and aquaporins, and
      suggest that the presence of these proteins is an adaptation for increasing the
      speed of vesicle rupture and, consequently, the speed of the sliming response of
      hagfishes. 

PMID- 24737756
TI  - Foot speed, foot-strike and footwear: linking gait mechanics and running ground
      reaction forces.
AB  - Running performance, energy requirements and musculoskeletal stresses are
      directly related to the action-reaction forces between the limb and the ground.
      For human runners, the force-time patterns from individual footfalls can vary
      considerably across speed, foot-strike and footwear conditions. Here, we used
      four human footfalls with distinctly different vertical force-time waveform
      patterns to evaluate whether a basic mechanical model might explain all of them.
      Our model partitions the body's total mass (1.0 Mb) into two invariant mass
      fractions (lower limb=0.08, remaining body mass=0.92) and allows the
      instantaneous collisional velocities of the former to vary. The best fits
      achieved (R(2) range=0.95-0.98, mean=0.97 +/- 0.01) indicate that the model is
      capable of accounting for nearly all of the variability observed in the four
      waveform types tested: barefoot jog, rear-foot strike run, fore-foot strike run
      and fore-foot strike sprint. We conclude that different running ground reaction
      force-time patterns may have the same mechanical basis.

PMID- 24737757
TI  - Optic flow and sea-land orientation in the sandhopper Talitrus saltator.
AB  - The problem sandhoppers face when they find themselves on the dry sand is to
      reach as quickly as possible the belt of moist sand near the water. In the
      present study, I ask whether, alongside many other orienting factors, sandhoppers
      use the optic flow they experience to maintain their bearing relative to the sea
      land axis. Adult individuals of Talitrus saltator were released in a transparent
      Plexiglas bowl, horizontally placed between four walls with a pattern of vertical
      black and white stripes. The orientation of one pair of opposite walls was south
      north, orthogonal to the sea-land axis of the home beach, whilst the second pair
      of walls was oriented east-west. The black and white striped pattern of opposite
      walls could be moved in pairs and in the same direction (speed=4.8 cm s(-1)). The
      results demonstrate that the optic flow sandhoppers experience when moving on the
      sea-land axis of their home beach influences their direction of travel and could
      help sandhoppers in maintaining a straight path to reach favourable ground by the
      shortest route. 

PMID- 24737758
TI  - Do Tetranychus urticae males avoid mating with familiar females?
AB  - The two-spotted spider mite, Tetranychus urticae, usually lives in kin groups
      under common webs. Because only the first mating results in fertilisation in
      female T. urticae, adult males guard quiescent deutonymph females, those at the
      stage immediately before maturation, to ensure paternity. Therefore, the cost of
      precopulatory guarding time seems considerable for males. Moreover, the fitness
      indices of daughters from intra-population crosses were significantly lower than
      those of daughters from inter-population crosses, indicating that inbreeding
      depression exists in T. urticae. Therefore, we hypothesised that T. urticae males
      should be choosy in guarding familiar females to avoid inbreeding depression.
      Furthermore, webs should be a key element of the environment shared by familiar
      individuals. In this study, we demonstrated the inbreeding avoidance mechanism of
      T. urticae males in relation to webs produced by familiar females (known webs) or
      unfamiliar females (unknown webs). Regardless of surrounding webs (known or
      unknown), males preferred unfamiliar to familiar females. We further examined
      whether males detect unfamiliar females by their webs. When males had experienced
      a female's web without encountering that female, they subsequently preferred
      females that did not produce the surrounding webs in which the choice experiment
      was conducted. Results suggest that putative kin recognition for inbreeding
      avoidance in T. urticae males is based on the relationship between webs and
      females, and not on the discrimination of webs in shared environments. 

PMID- 24737759
TI  - Novel underwater soundscape: acoustic repertoire of plainfin midshipman fish.
AB  - Toadfishes are among the best-known groups of sound-producing (vocal) fishes and
      include species commonly known as toadfish and midshipman. Although midshipman
      have been the subject of extensive investigation of the neural mechanisms of
      vocalization, this is the first comprehensive, quantitative analysis of the
      spectro-temporal characters of their acoustic signals and one of the few for
      fishes in general. Field recordings of territorial, nest-guarding male midshipman
      during the breeding season identified a diverse vocal repertoire composed of
      three basic sound types that varied widely in duration, harmonic structure and
      degree of amplitude modulation (AM): 'hum', 'grunt' and 'growl'. Hum duration
      varied nearly 1000-fold, lasting for minutes at a time, with stable harmonic
      stacks and little envelope modulation throughout the sound. By contrast, grunts
      were brief, ~30-140 ms, broadband signals produced both in isolation and
      repetitively as a train of up to 200 at intervals of ~0.5-1.0 s. Growls were also
      produced alone or repetitively, but at variable intervals of the order of seconds
      with durations between those of grunts and hums, ranging 60-fold from ~200 ms to
      12 s. Growls exhibited prominent harmonics with sudden shifts in pulse repetition
      rate and highly variable AM patterns, unlike the nearly constant AM of grunt
      trains and flat envelope of hums. Behavioral and neurophysiological studies
      support the hypothesis that each sound type's unique acoustic signature
      contributes to signal recognition mechanisms. Nocturnal production of these
      sounds against a background chorus dominated constantly for hours by a single
      sound type, the multi-harmonic hum, reveals a novel underwater soundscape for
      fish. 

PMID- 24737760
TI  - The four aldehyde oxidases of Drosophila melanogaster have different gene
      expression patterns and enzyme substrate specificities.
AB  - In the genome of Drosophila melanogaster, four genes coding for aldehyde oxidases
      (AOX1-4) were identified on chromosome 3. Phylogenetic analysis showed that the
      AOX gene cluster evolved via independent duplication events in the vertebrate and
      invertebrate lineages. The functional role and the substrate specificity of the
      distinct Drosophila AOX enzymes is unknown. Two loss-of-function mutant alleles
      in this gene region, low pyridoxal oxidase (Po(lpo)) and aldehyde oxidase-1
      (Aldox-1(n1)) are associated with a phenotype characterized by undetectable AOX
      enzymatic activity. However, the genes involved and the corresponding mutations
      have not yet been identified. In this study we characterized the activities,
      substrate specificities and expression profiles of the four AOX enzymes in D.
      melanogaster. We show that the Po(lpo)-associated phenotype is the consequence of
      a structural alteration of the AOX1 gene. We identified an 11-bp deletion in the
      Po(lpo) allele, resulting in a frame-shift event, which removes the molybdenum
      cofactor domain of the encoded enzyme. Furthermore, we show that AOX2 activity is
      detectable only during metamorphosis and characterize a Minos-AOX2 insertion in
      this developmental gene that disrupts its activity. We demonstrate that the Aldox
      1(n1) phenotype maps to the AOX3 gene and AOX4 activity is not detectable in our
      assays. 

PMID- 24737761
TI  - Olfactory learning and memory in the disease vector mosquito Aedes aegypti.
AB  - Olfactory learning in blood-feeding insects, such as mosquitoes, could play an
      important role in host preference and disease transmission. However, standardised
      protocols allowing testing of their learning abilities are currently lacking, and
      how different olfactory stimuli are learned by these insects remains unknown.
      Using a Pavlovian conditioning paradigm, we trained individuals and groups of
      Aedes aegypti mosquitoes to associate an odorant conditioned stimulus (CS) with a
      blood-reinforced thermal stimulus (unconditioned stimulus; US). Results showed,
      first, that mosquitoes could learn the association between L-lactic acid and the
      US, and retained the association for at least 24 h. Second, the success of
      olfactory conditioning was dependent upon the CS--some odorants that elicited
      indifferent responses in naive mosquitoes, such as L-lactic acid and 1-octen-3
      ol, were readily learned, whereas others went from aversive to attractive after
      training (Z-3-hexen-1-ol) or were untrainable (beta-myrcene and benzyl alcohol).
      Third, we examined whether mosquitoes' ability to learn could interfere with the
      action of the insect repellent DEET. Results demonstrated that pre-exposure and
      the presence of DEET in the CS reduced the aversive effects of DEET. Last, the
      nature of the formed memories was explored. Experiments using cold-shock
      treatments within the first 6 h post-training (for testing anaesthesia-resistant
      memory) and a protein synthesis inhibitor (cycloheximide; to disrupt the
      formation of long-term memory) both affected mosquitoes' performances. Together,
      these results show that learning is a crucial component in odour responses in A.
      aegypti, and provide the first evidence for the functional role of different
      memory traces in these responses.

PMID- 24737762
TI  - Wood frog adaptations to overwintering in Alaska: new limits to freezing
      tolerance.
AB  - We investigated the ecological physiology and behavior of free-living wood frogs
      [Lithobates (Rana) sylvaticus] overwintering in Interior Alaska by tracking
      animals into natural hibernacula, recording microclimate, and determining frog
      survival in spring. We measured cryoprotectant (glucose) concentrations and
      identified the presence of antifreeze glycolipids in tissues from subsamples of
      naturally freezing frogs. We also recorded the behavior of wood frogs preparing
      to freeze in artificial hibernacula, and tissue glucose concentrations in captive
      wood frogs frozen in the laboratory to -2.5 degrees C. Wood frogs in natural
      hibernacula remained frozen for 193 +/- 11 consecutive days and experienced
      average (October-May) temperatures of -6.3 degrees C and average minimum
      temperatures of -14.6 +/- 2.8 degrees C (range -8.9 to -18.1 degrees C) with 100%
      survival (N=18). Mean glucose concentrations were 13-fold higher in muscle, 10
      fold higher in heart and 3.3-fold higher in liver in naturally freezing compared
      with laboratory frozen frogs. Antifreeze glycolipid was present in extracts from
      muscle and internal organs, but not skin, of frozen frogs. Wood frogs in Interior
      Alaska survive freezing to extreme limits and durations compared with those
      described in animals collected in southern Canada or the Midwestern United
      States. We hypothesize that this enhancement of freeze tolerance in Alaskan wood
      frogs is due to higher cryoprotectant levels that are produced by repeated
      freezing and thawing cycles experienced under natural conditions during early
      autumn.

PMID- 24737763
TI  - Diurnal dung beetles use the intensity gradient and the polarization pattern of
      the sky for orientation.
AB  - To escape competition at the dung pile, a ball-rolling dung beetle forms a piece
      of dung into a ball and rolls it away. To ensure their efficient escape from the
      dung pile, beetles rely on a 'celestial compass' to move along a straight path.
      Here, we analyzed the reliability of different skylight cues for this compass and
      found that dung beetles rely not only on the sun but also on the skylight
      polarization pattern. Moreover, we show the first evidence of an insect using the
      celestial light-intensity gradient for orientation. Using a polarizer, we
      manipulated skylight so that the polarization pattern appeared to turn by 90 deg.
      The beetles then changed their bearing close to the expected 90 deg. This
      behavior was abolished if the sun was visible to the beetle, suggesting that
      polarized light is hierarchically subordinate to the sun. When the sky was
      depolarized and the sun was invisible, the beetles could still move along
      straight paths. Therefore, we analyzed the use of the celestial light-intensity
      gradient for orientation. Artificial rotation of the intensity pattern by 180 deg
      caused beetles to orient in the opposite direction. This light-intensity cue was
      also found to be subordinate to the sun and could play a role in disambiguating
      the polarization signal, especially at low sun elevations. 

PMID- 24737764
TI  - Trpc2 is expressed in two olfactory subsystems, the main and the vomeronasal
      system of larval Xenopus laevis.
AB  - Complete segregation of the main olfactory epithelium (MOE) and the vomeronasal
      epithelium is first observed in amphibians. In contrast, teleost fishes possess a
      single olfactory surface, in which genetic components of the main and vomeronasal
      olfactory systems are intermingled. The transient receptor potential channel
      TRPC2, a marker of vomeronasal neurons, is present in the single fish sensory
      surface, but is already restricted to the vomeronasal epithelium in a terrestrial
      amphibian, the red-legged salamander (Plethodon shermani). Here we examined the
      localization of TRPC2 in an aquatic amphibian and cloned the Xenopus laevis trpc2
      gene. We show that it is expressed in both the MOE and the vomeronasal
      epithelium. This is the first description of a broad trpc2 expression in the MOE
      of a tetrapod. The expression pattern of trpc2 in the MOE is virtually
      undistinguishable from that of MOE-specific v2rs, indicating that they are co
      expressed in the same neuronal subpopulation. 

PMID- 24737765
TI  - What a jerk: prey engulfment revealed by high-rate, super-cranial accelerometry
      on a harbour seal (Phoca vitulina).
AB  - A key component in understanding the ecological role of marine mammal predators
      is to identify how and where they capture prey in time and space. Satellite and
      archival tags on pinnipeds generally only provide diving and position
      information, and foraging is often inferred to take place in particular shaped
      dives or when the animal remains in an area for an extended interval. However,
      fast movements of the head and jaws may provide reliable feeding cues that can be
      detected by small low-power accelerometers mounted on the head. To test this
      notion, a harbour seal (Phoca vitulina) was trained to wear an OpenTag (sampling
      at 200 or 333 Hz with +/- 2 or +/- 16 g clipping) on its head while catching fish
      prey in front of four underwater digital high-speed video cameras. We show that
      both raptorial and suction feeding generate jerk (i.e. differential of
      acceleration) signatures with maximum peak values exceeding 1000 m s(-3). We
      conclude that reliable prey capture cues can be derived from fast-sampling, head
      mounted accelerometer tags, thus holding a promising potential for long-term
      studies of foraging ecology and field energetics of aquatic predators in their
      natural environments.

PMID- 24737766
TI  - Reduced consumption of protein-rich foods follows immune challenge in a
      polyphagous caterpillar.
AB  - Advances in ecological immunity have illustrated that, like vertebrates, insects
      exhibit adaptive immunity, including induced changes in feeding behavior that aid
      the immune system. In particular, recent studies have pointed to the importance
      of protein intake in mounting an immune response. In this study, we tested the
      hypothesis that the polyphagous caterpillar Grammia incorrupta (H. Edwards)
      (Family: Erebidae) would adaptively change its feeding behavior in response to
      immune challenge, predicting that caterpillars would increase their intake of
      dietary protein. We further predicted that this response would enhance the
      melanization response, a component of the immune system that acts against
      parasitoids. We challenged the immune system using either tachinid fly
      parasitoids or a bead injection technique that has been used in studies to
      simulate parasitism, and measured feeding before and after immune challenge on
      diets varying in their macronutrient content. To evaluate the effects of diet on
      melanization, we quantified melanization of beads following feeding assays.
      Contrary to our prediction, we found that parasitized or injected caterpillars
      given a choice between high- and low-protein foods reduced their intake of the
      high-protein food. Furthermore, in a no-choice experiment, caterpillars offered
      food with a protein concentration that is optimal for growth reduced feeding
      following immune challenge, whereas those offered a low-protein food did not.
      Although variation in protein intake did not change the caterpillars'
      melanization response, increased carbohydrate intake did increase melanization,
      suggesting a prophylactic role for carbohydrates. We discuss alternative
      mechanisms by which variation in protein intake could negatively or positively
      affect parasitized caterpillars, including nutritional interactions with the
      caterpillar's self-medication response. 

PMID- 24737767
TI  - Phase shifts in binaural stimuli provide directional cues for sound localisation
      in the field cricket Gryllus bimaculatus.
AB  - The cricket's auditory system is a highly directional pressure difference
      receiver whose function is hypothesised to depend on phase relationships between
      the sound waves propagating through the auditory trachea that connects the left
      and right hearing organs. We tested this hypothesis by measuring the effect of
      experimentally constructed phase shifts in acoustic stimuli on phonotactic
      behavior of Gryllus bimaculatus, the oscillatory response patterns of the
      tympanic membrane, and the activity of the auditory afferents. The same
      artificial calling song was played simultaneously at the left and right sides of
      the cricket, but one sound pattern was shifted in phase by 90 deg (carrier
      frequencies between 3.6 and 5.4 kHz). All three levels of auditory processing are
      sensitive to experimentally induced acoustic phase shifts, and the response
      characteristics are dependent on the carrier frequency of the sound stimulus. At
      lower frequencies, crickets steered away from the sound leading in phase, while
      tympanic membrane vibrations and auditory afferent responses were smaller when
      the ipsilateral sound was leading. In contrast, opposite responses were observed
      at higher frequencies in all three levels of auditory processing. Minimal
      responses occurred near the carrier frequency of the cricket's calling song,
      suggesting a stability at this frequency. Our results indicate that crickets may
      use directional cues arising from phase shifts in acoustic signals for sound
      localisation, and that the response properties of pressure difference receivers
      may be analysed with phase-shifted sound stimuli to further our understanding of
      how insect auditory systems are adapted for directional processing. 

PMID- 24737768
TI  - Null point of discrimination in crustacean polarisation vision.
AB  - The polarisation of light is used by many species of cephalopods and crustaceans
      to discriminate objects or to communicate. Most visual systems with this ability,
      such as that of the fiddler crab, include receptors with photopigments that are
      oriented horizontally and vertically relative to the outside world.
      Photoreceptors in such an orthogonal array are maximally sensitive to polarised
      light with the same fixed e-vector orientation. Using opponent neural
      connections, this two-channel system may produce a single value of polarisation
      contrast and, consequently, it may suffer from null points of discrimination.
      Stomatopod crustaceans use a different system for polarisation vision, comprising
      at least four types of polarisation-sensitive photoreceptor arranged at 0, 45, 90
      and 135 deg relative to each other, in conjunction with extensive rotational eye
      movements. This anatomical arrangement should not suffer from equivalent null
      points of discrimination. To test whether these two systems were vulnerable to
      null points, we presented the fiddler crab Uca heteropleura and the stomatopod
      Haptosquilla trispinosa with polarised looming stimuli on a modified LCD monitor.
      The fiddler crab was less sensitive to differences in the degree of polarised
      light when the e-vector was at -45 deg than when the e-vector was horizontal. In
      comparison, stomatopods showed no difference in sensitivity between the two
      stimulus types. The results suggest that fiddler crabs suffer from a null point
      of sensitivity, while stomatopods do not.

PMID- 24737769
TI  - Rapid swimming and escape movements in the aquatic larvae and pupae of the
      phantom midge Chaoborus crystallinus.
AB  - Rapid locomotion in the aquatic larvae and pupae of the phantom midge Chaoborus
      crystallinus was analysed. A 10-mm long larva moved sporadically by rapidly
      curling into a tight circle and then unfurling. The most common movement (70% of
      all movements) was a body rotation of 332+/-22 deg (mean +/- s.d.) that lasted
      63+/-19 ms and reached a peak velocity of 0.07+/-0.02 m s(-1). If the head
      unfurled earlier in the cycle, the rotation was smaller and the larva dived
      downwards. A distinct category of single rotations of approximately 180 deg (8%)
      resulted in a larva finishing with its head pointing in the opposite direction. A
      sequence of rotational movements (22%) resulted in more extensive displacements.
      The area of the tail fan was reduced by folding during part of a cycle. It was
      made of a row of 26 radiating filaments with interlacing hairs between adjacent
      filaments and resilin at their ventral midline articulations with the body. The
      fan sprang back passively to its splayed position after being forcibly folded.
      Reducing the area of the fan by 80% decreased angular rotation and impaired
      stability so that 33% of movements ended with the body upside down. A 6 mm long
      pupa also moved by curling and unfurling motions of the head and tail that lasted
      215+/-19 ms and generated slower velocities of 0.03+/-0.01 m s(-1). The pupal
      tail fan was membranous, oriented differently, had resilin at its articulations
      and its area could be changed.

PMID- 24737770
TI  - Is there metabolic cold adaptation in terrestrial ectotherms? Exploring
      latitudinal compensation in the invasive snail Cornu aspersum.
AB  - Lower temperatures, extreme seasonality and shorter growing seasons at higher
      latitudes are expected to cause a decline in metabolic rates and annual growth
      rates of ectotherms. If a reduction in the rates of these biological processes
      involves a reduction in fitness, then organisms may evolve compensatory responses
      for the constraints imposed by high-latitude habitats. To test the existence of a
      latitudinal compensation in ectotherms, we used a common-garden experiment to
      investigate the extent to which the level of energy turnover (measured as
      standard metabolic rate, SMR) and the energy budget (energy allocation to growth)
      are affected by climatic constraints in three populations of the land snail Cornu
      aspersum, distributed across a latitudinal gradient of 1300 km in Chile. Our
      results did not support the existence of a latitudinal compensation in metabolic
      rates (metabolic cold adaptation). However, there was a countergradient variation
      (CnGV) for growth rate in which the highest latitudinal population exhibited
      greater growth rates than their counterparts from lower latitudes. Surprisingly,
      this CnGV pattern was accompanied by a lower apparent dry-matter digestibility,
      which could highlight a differential assimilation of ingested nutrients into
      somatic tissue, revealing enhanced growth efficiency in snails from the highest
      latitudinal habitat. Our evidence highlights that adjustments in energy
      allocation to the digestive machinery and to protein storage could act as a
      latitudinal compensation for enhanced growth efficiency in snails from the
      highest latitudinal population. 

PMID- 24737771
TI  - Sedentary behavior as a factor in determining lateral line contributions to
      rheotaxis.
AB  - Rheotaxis is a robust, multisensory behavior with many potential benefits for
      fish and other aquatic animals. Visual (optic flow) cues appear to be sufficient
      for rheotaxis, but other sensory cues can clearly compensate for the loss of
      vision. The role of various non-visual sensory systems, in particular the flow
      sensing lateral line, is poorly understood, largely because of widely varying
      methods and sensory conditions for studying rheotaxis. Here, we examine how
      sedentary behavior under visually deprived conditions affects the relative
      importance of lateral line cues in two species: one that is normally sedentary
      (the three-lined corydoras, Corydoras trilineatus) and one that normally swims
      continuously along the substrate (the blind cavefish, Astyanax mexicanus). No
      effect of lateral line disruption on rheotactic performance was found in blind
      cavefish, which were significantly more mobile than three-lined corydoras. By
      contrast, rheotaxis was significantly impaired at low, but not high, flow speeds
      in lateral-line-disabled corydoras. In addition, lateral-line-enabled corydoras
      were characterized by decreased mobility and increased rheotactic performance
      relative to lateral-line-disabled fish. Taken together, these results suggest
      that sedentary behavior is an important factor in promoting reliance on lateral
      line cues. 

PMID- 24737772
TI  - Energy metabolism and regeneration are impaired by seawater acidification in the
      infaunal brittlestar Amphiura filiformis.
AB  - Seawater acidification due to anthropogenic release of CO2 as well as the
      potential leakage of pure CO2 from sub-seabed carbon capture storage (CCS) sites
      may impose a serious threat to marine organisms. Although infaunal organisms can
      be expected to be particularly impacted by decreases in seawater pH, as a result
      of naturally acidified conditions in benthic habitats, information regarding
      physiological and behavioral responses is still scarce. Determination of PO2 and
      P(CO2) gradients within burrows of the brittlestar Amphiura filiformis during
      environmental hypercapnia demonstrated that besides hypoxic conditions, increases
      of environmental P(CO2) are additive to the already high P(CO2) (up to 0.08 kPa)
      within the burrows. In response to up to 4 weeks exposure to pH 7.3 (0.3 kPa
      P(CO2)) and pH 7.0 (0.6 kPa P(CO2)), metabolic rates of A. filiformis were
      significantly reduced in pH 7.0 treatments, accompanied by increased ammonium
      excretion rates. Gene expression analyses demonstrated significant reductions of
      acid-base (NBCe and AQP9) and metabolic (G6PDH, LDH) genes. Determination of
      extracellular acid-base status indicated an uncompensated acidosis in CO2-treated
      animals, which could explain the depressed metabolic rates. Metabolic depression
      is associated with a retraction of filter feeding arms into sediment burrows.
      Regeneration of lost arm tissues following traumatic amputation is associated
      with significant increases in metabolic rate, and hypercapnic conditions (pH 7.0,
      0.6 kPa) dramatically reduce the metabolic scope for regeneration, reflected in
      an 80% reduction in regeneration rate. Thus, the present work demonstrates that
      elevated seawater P(CO2) significantly affects the environment and the physiology
      of infaunal organisms like A. filiformis.

PMID- 24737773
TI  - Improving contraceptive choice: fidelity of implementation and the gap between
      effectiveness and efficacy.
AB  - Interventions to reduce unintended pregnancy through improved contraceptive use
      are a public health priority. A comprehensive process evaluation of a
      contraceptive assessment module intervention with demonstrated efficacy was
      undertaken. The 12-month process evaluation goal was to describe the extent to
      which the intervention was implemented as intended over time, and to identify
      programmatic adjustments to improve implementation fidelity. Quantitative and
      qualitative methods included staff surveys, electronic health record data, usage
      monitoring, and observations. Fidelity of implementation was low overall (<10% of
      eligible patients completed the entire module [dose received]). Although a
      midcourse correction making the module available in clinical areas led to
      increased dose delivered (23% vs. 30%, chi-square test p = .006), dose received
      did not increase significantly after this adjustment. Contextual factors
      including competing organizational and staff priorities and staff buy-in limited
      the level of implementation and precluded adoption of some strategies such as
      adjusting patient flow. Using a process evaluation framework enabled the research
      team to identify and address complexities inherent in effectiveness studies and
      facilitated the alignment of program and context. 

PMID- 24737774
TI  - Peer mentoring is associated with positive change in physical activity and
      aerobic fitness of grades 4, 5, and 6 students in the heart healthy kids program.
AB  - Only 7% of Canadian children achieve activity recommendations, contributing to
      obesity and preventable disease. The Heart Healthy Kids (H2K) program was
      designed to test the relationship between peer mentoring, physical activity, and
      cardiovascular fitness. Participants from 10 schools (5 control, 5 intervention)
      were enrolled in the program. In control schools, H2K included a physical
      activity challenge and education sessions. Intervention schools included the
      addition of a peer-mentoring component. Physical activity was measured through
      daily pedometer recording. Cardiovascular fitness was evaluated using the PACER
      (Progressive Aerobic Cardiovascular Endurance Run) protocol to calculate maximal
      oxygen uptake (VO2 max). Participants included 808 children (average age 9.9 +/-
      1.0 years). Although control and intervention schools did not differ at baseline,
      participants with peer mentoring logged significantly more steps per school day,
      on average, than those in control schools (6,785 +/- 3,011 vs. 5,630 +/- 2,586; p
      < .001). Male participants logged significantly more steps per school day than
      female participants. A significant improvement in VO2 max was also noted in
      intervention schools, with an average increase of 1.72 ml/mg/min. H2K was
      associated with positive change in physical activity and cardiovascular fitness,
      suggesting that peer mentoring shows promise for application in health promotion
      interventions. 

PMID- 24737775
TI  - Our world through our eyes: adolescents use photovoice to speak their mind on
      adolescent health, well-being, and sexuality in Lima, Peru.
AB  - Peru's approach to its 5.7 million 10- to 19-year-olds has shifted toward
      positive youth development. Following that trend, our objective was to facilitate
      Peruvian adolescents' use of photovoice to better understand the factors
      affecting their health, well-being, and sexuality and to work with adolescents to
      present policy and programmatic recommendations. Photovoice sessions were carried
      out with low-income 12- to 16-year-olds (n = 13) from Lima. Sessions included
      basic photography and ethics, photo taking, and descriptions and discussions
      using the SHOWeD (What do you See here? What is really Happening? How does this
      relate to Our lives? Why does this problem or strength exist? What can we Do
      about it?) method. Participants grouped their photos into a "photo story." Each
      section of the story consisted of a message and 4 to 10 photos. Each photo had a
      caption that answered the SHOWeD questions. Messages were (a) "health and well
      being in danger of extinction," (b) "with some signs of hope," (c) "innocence in
      spite of everything," (d) "what we as adolescents have," and (e) "but we lack
      opportunities to live a better life and a responsible sexuality." Participants
      presented the photo story to program planners, policy makers, and community
      members. Results underscore the value of including adolescents in program and
      policy planning and affirm that photovoice can achieve such inclusion. Photovoice
      provides a concrete method for adolescents to speak their mind through image and
      word. 

PMID- 24737776
TI  - Quantitative assessment of manual and robotic microcannulation for eye surgery
      using new eye model.
AB  - BACKGROUND: Microcannulation, a surgical procedure for the eye that requires drug
      injection into a 60-90 um retinal vein, is difficult to perform manually. Robotic
      assistance has been proposed; however, its effectiveness in comparison to manual
      operation has not been quantified. METHODS: An eye model has been developed to
      quantify the performance of manual and robotic microcannulation. The eye model,
      which is implemented with a force sensor and microchannels, also simulates the
      mechanical constraints of the instrument's movement. Ten subjects performed
      microcannulation using the model, with and without robotic assistance. RESULTS:
      The results showed that the robotic assistance was useful for motion stability
      when the drug was injected, whereas its positioning accuracy offered no
      advantage. CONCLUSIONS: An eye model was used to quantitatively assess the
      robotic microcannulation performance in comparison to manual operation. This
      approach could be valid for a better evaluation of surgical robotic assistance.

PMID- 24737777
TI  - Cancer phenotypic lethality, exemplified by the non-essential MTH1 enzyme being
      required for cancer survival.

PMID- 24737778
TI  - A phase I dose escalation study of oral c-MET inhibitor tivantinib (ARQ 197) in
      combination with gemcitabine in patients with solid tumors.
AB  - BACKGROUND: Tivantinib (ARQ 197) is an orally available, non-adenosine
      triphosphate competitive, selective c-MET inhibitor. The primary objective of
      this study was to evaluate the safety, tolerability and to establish the
      recommended phase II dose (RP2D) of tivantinib and gemcitabine combination.
      PATIENTS AND METHODS: Patients with advanced or metastatic solid tumors were
      treated with escalating doses of tivantinib (120-360 mg capsules) in combination
      with gemcitabine (1000 mg/m(2) weekly for 3 of 4 weeks). Different schedules of
      administration were tested and modified based on emerging preclinical data.
      Tivantinib was given continuously, twice a day (b.i.d.) for 2, 3 or 4 weeks of a
      28-day cycle or on a 5-day on, 2-day off schedule (the day before and day of
      gemcitabine administration). RESULTS: Twenty-nine patients were treated with
      gemcitabine and escalating doses of tivantinib: 120 mg b.i.d. (n = 4), 240 mg
      b.i.d. (n = 6) and 360 mg b.i.d. (n = 19). No dose-limiting toxicities were
      observed in escalation. The RP2D was 360 mg b.i.d. daily, and 45 additional
      patients were enrolled in the expansion cohort. Grade >=3 treatment-related
      toxicities were observed in 54 of 74 (73%) patients with the most common being
      neutropenia (43%), anemia (30%), thrombocytopenia (28%) and fatigue (15%). There
      was one treatment-related death due to neutropenia. Administration of gemcitabine
      did not affect tivantinib concentration. Fifty-six patients were assessable for
      response. Eleven (20%) patients achieved a partial response and 26 (46%) had
      stable disease (SD), including 15 (27%) who achieved SD for over 4 months. Ten of
      37 patients with clinical benefit had prior exposure to gemcitabine. CONCLUSION:
      The combination of tivantinib at its monotherapy dose and standard dose
      gemcitabine was safe and tolerable. Early signs of antitumor activity may warrant
      further development of this combination in nonsmall-cell lung cancer, ovarian,
      pancreatic and cholangiocarcinoma. CLINICALTRIALSGOV IDENTIFIER: NCT00874042.

PMID- 24737779
TI  - Hepatic arterial infusion chemotherapy with cisplatin before radical local
      treatment of early hepatocellular carcinoma (JIS score 0/1) improves survival.
AB  - BACKGROUND: It has not yet been determined whether hepatic arterial infusion
      (HAI) chemotherapy improves survival in patients with early hepatocellular
      carcinoma (HCC). We evaluated the effectiveness of HAI with high-concentration
      cisplatin (DDP-H) for the treatment of HCC by comparing outcomes between patients
      who received HAI with DDP-H before radical local treatment of early-stage HCC
      [Japan Integrated Staging (JIS) score 0/1] and patients who did not receive HAI
      chemotherapy. PATIENTS AND METHODS: Survival was analyzed in 114 patients with
      early-stage HCC who underwent radical local treatment. The patients were divided
      into two groups: a HAI group (n = 79) who received DDP-H infusion into the whole
      liver via the proper hepatic artery, and a non-HAI group (n = 35) who did not
      receive HAI chemotherapy. RESULTS: The cumulative survival rates at 1, 3, and 5
      years were 77.4%, 69.2%, and 55.3% in the non-HAI group and 97.4%, 87.0%, and
      84.4% in the HAI group, respectively. Survival time prolonged significantly in
      the HAI group compared with the non-HAI group (log-rank test: P = 0.023;
      generalized Wilcoxon test: P = 0.012) Multivariate analysis using the Cox
      proportional hazards model identified HAI with DDP-H as the most important factor
      affecting survival. CONCLUSIONS: Whole-liver HAI with DDP-H before radical local
      treatment can improve the prognosis of patients with early-stage HCC.

PMID- 24737781
TI  - What a difference two days make: "personalized" embryo transfer (pET) paradigm: a
      case report and pilot study.
AB  - Embryo implantation requires that the blastocyst will attach during the receptive
      stage of the endometrium, known as window of implantation (WOI). Historically, it
      has been assumed that the WOI is always constant in all women. However, molecular
      analyses of endometrial receptivity demonstrates a personalized WOI (pWOI) that
      is displaced in one out of four patients suffering from recurrent implantation
      failure (RIF) of endometrial origin and illustrates the utility of a personalized
      endometrial diagnostic approach. Here, we report a clinical case of successful
      personalized embryo transfer (pET) after four IVF and three oocyte donation
      failed attempts in which different embryo transfer strategies were attempted.
      This case report is complemented by a pilot study of 17 patients undergoing
      oocyte donation and who suffered failed implantations with routine embryo
      transfer (ET) but were then treated with pET after the personalized diagnosis of
      their WOI. 

PMID- 24737780
TI  - Angiomodulin, a marker of cancer vasculature, is upregulated by vascular
      endothelial growth factor and increases vascular permeability as a ligand of
      integrin alphavbeta3.
AB  - Angiomodulin (AGM) is a member of insulin-like growth factor binding protein
      (IGFBP) superfamily and often called IGFBP-rP1 or IGFBP-7. AGM was originally
      identified as a tumor-derived cell adhesion factor, which was highly accumulated
      in blood vessels of human cancer tissues. AGM is also overexpressed in cancer
      associated fibroblasts (CAFs) and activates fibroblasts. However, some studies
      have shown tumor-suppressing activity of AGM. To understand the roles of AGM in
      cancer progression, we here investigated the expression of AGM in benign and
      invasive breast cancers and its functions in cancer vasculature.
      Immunohistochemical analysis showed that AGM was highly expressed in cancer
      vasculature even in ductal carcinoma in situ (DCIS) as compared to normal
      vasculature, while its expression in CAFs was more prominent in invasive
      carcinomas than DCIS. In vitro analyses showed that AGM was strongly induced by
      vascular endothelial cell growth factor (VEGF) in vascular endothelial cells.
      Although AGM stimulated neither the growth nor migration of endothelial cells, it
      supported efficient adhesion of endothelial cells. Integrin alphavbeta3 was
      identified as a novel major receptor for AGM in vascular endothelial cells. AGM
      retracted endothelial cells by inducing actin stress fibers and loosened their VE
      cadherin-mediated intercellular junction. Consequently, AGM increased vascular
      permeability both in vitro and in vivo. Furthermore, AGM and integrin alphavbeta3
      were highly expressed and colocalized in cancer vasculature. These results
      suggest that AGM cooperates with VEGF to induce the aberrant functions of cancer
      vasculature as a ligand of integrin alphavbeta3.

PMID- 24737782
TI  - Multilocus Characterization of a Woodrat (Genus Neotoma) Hybrid Zone.
AB  - In order to investigate hybridization between 2 species of woodrats, Neotoma
      floridana and Neotoma micropus, 103 specimens were collected, in March of 1988,
      from a known area of sympatry, and compared with reference collections from areas
      of allopatry. Ten genetic markers, consisting of 7 microsatellite loci, 1
      mitochondrial gene (cytochrome-b [Cytb]), and 2 nuclear introns (intron 2 of the
      vertebrate alcohol dehydrogenase gene [Adh1-I2] and intron 7 of the beta
      fibrinogen gene [Fgb-I7]) were used to develop a composite genotype for each
      individual and for detection of hybridization. Six individuals were identified as
      pure parental N. micropus, 96 as hybrids, and 1 as pure parental N. floridana
      Hybrids were formed primarily through matings between complex genotypes,
      resulting in a high prevalence of individuals classified as backcrosses. The
      ratio of hybrid classes, population substructure, and presence of significant
      linkage disequilibrium within the zone of contact could not reject either the
      hybrid superiority or hybrid equilibrium model as responsible for maintenance of
      this hybrid zone. The collection date of this dataset (1988) provided not only a
      point in time assessment of the hybrid zone but also provided opportunities for
      future comparisons of temporal datasets with the purpose of examining hybrid zone
      characteristics over multiple generations.

PMID- 24737783
TI  - Biocatalytic reduction of carboxylic acids.
AB  - An increasing demand for non-petroleum-based products is envisaged in the near
      future. Carboxylic acids such as citric acid, succinic acid, fatty acids, and
      many others are available in abundance from renewable resources and they could
      serve as economic precursors for bio-based products such as polymers, aldehyde
      building blocks, and alcohols. However, we are confronted with the problem that
      carboxylic acid reduction requires a high level of energy for activation due to
      the carboxylate's thermodynamic stability. Catalytic processes are scarce and
      often their chemoselectivity is insufficient. This review points at bio
      alternatives: currently known enzyme classes and organisms that catalyze the
      reduction of carboxylic acids are summarized. Two totally distinct biocatalyst
      lines have evolved to catalyze the same reaction: aldehyde oxidoreductases from
      anaerobic bacteria and archea, and carboxylate reductases from aerobic sources
      such as bacteria, fungi, and plants. The majority of these enzymes remain to be
      identified and isolated from their natural background in order to evaluate their
      potential as industrial biocatalysts. 

PMID- 24737784
TI  - Investigation of cyanine dyes for in vivo optical imaging of altered
      mitochondrial membrane potential in tumors.
AB  - Mitochondrial membrane potential (Deltapsim ) alteration is an important target
      for cancer diagnosis. In this study, we designed a series of near-infrared
      fluorescent cationic cyanine dyes with varying alkyl chain lengths (IC7-1
      derivatives) to provide diverse lipophilicities and serum albumin-binding rates,
      and we evaluated the usefulness of these derivatives for in vivo Deltapsim
      imaging. IC7-1 derivatives with side chains from methyl to hexyl (IC7-1-Me to IC7
      1-He) were synthesized, and their optical properties were measured. Cellular
      uptake and intracellular distribution were investigated with depolarized HeLa
      cells from carbonyl cyanine m-chlorophenylhydrazone (CCCP) treatment using a
      spectrofluorometer and a fluorescence microscope. Serum albumin-binding rates
      were evaluated using albumin-binding inhibitors. In vivo optical imaging was
      performed with HeLa cell xenograft mice following intravenous administration of
      IC7-1 derivatives with or without warfarin and CCCP as in vivo blocking agents.
      IC7-1 derivatives showing maximum excitation and emission wavelengths at 823 nm
      and ~845 nm, respectively, were synthesized. IC7-1-Me to -Bu showed fluorescence
      in mitochondria that decreased with CCCP treatment in a concentration-dependent
      manner, which showed that IC7-1-Me to -Bu successfully indicated Deltapsim .
      Tumors were clearly visualized after IC7-1-Bu administration. Treatment with
      warfarin or CCCP significantly decreased IC7-1-Bu fluorescence in the tumor
      region. In summary, IC7-1-Bu exhibited fluorescence localized to mitochondria
      dependent on Deltapsim , which enabled clear in vivo tumor imaging via serum
      albumin as a drug carrier for effective tumor targeting. Our data suggest that
      IC7-1-Bu is a promising NIR probe for in vivo imaging of the altered Deltapsim of
      tumor cells.

PMID- 24737785
TI  - The effect of a nematode parasite on feeding and dung-burying behavior of an
      ecosystem engineer.
AB  - Dung beetles (genus Phanaeus) consume feces in both their larval and adults forms
      and because of their unique dietary niche, and behaviors associated with the
      burial of feces, are considered ecosystem engineers. In addition, because these
      insects subsist on a diet composed exclusively of feces, it is likely they
      encounter parasitic propagules more frequently than other animals do. Parasites
      often alter their host's behavior, so we set out to test whether Physocephalus
      sexalatus (a cosmopolitan nematode parasite of ungulates) does so in ways that
      affect the dung beetle's role as an ecosystem engineer and/or its predator-prey
      relationships (transmission of the parasite). Classic tests of anti-predator
      behavior did not reveal behavioral differences based on the beetles' infection
      status. However, this parasite did alter the beetles' behaviors in ways that
      could be critical for its role in fecal processing and therefore ecosystem
      engineering. Infected beetles exhibited anorexic behavior and consumed only half
      the amount of feces ingested by similar uninfected beetles. Infected beetles also
      buried less feces and did so in tunnels that were significantly shorter than
      those created by uninfected beetles. Fecal burial is naturally beneficial because
      it aerates the soil, incorporates nitrogenous compounds, and increases the flow
      of water thereby making soil and pastureland more productive. We showed that the
      nematode parasite P. sexalatus itself becomes an ecosystem engineer as it
      modifies the behavior of its already influential intermediate host. 

PMID- 24737787
TI  - Complication of percutaneous endoscopic gastrostomy.

PMID- 24737786
TI  - Cost-effectiveness of infliximab versus conventional combination treatment in
      methotrexate-refractory early rheumatoid arthritis: 2-year results of the
      register-enriched randomised controlled SWEFOT trial.
AB  - OBJECTIVE: To estimate the incremental cost-effectiveness of infliximab versus
      conventional combination treatment over 21 months in patients with methotrexate
      refractory early rheumatoid arthritis. METHODS: In this multicentre, two-arm,
      parallel, randomised, active-controlled, open-label trial, rheumatoid arthritis
      patients with <1 year symptom duration were recruited from 15 rheumatology
      clinics in Sweden between October 2002 and December 2005. After 3-4 months of
      methotrexate monotherapy, patients not achieving low disease activity were
      randomised to addition of infliximab or sulfasalazine+hydroxychloroquine
      (conventional treatment group). Costs of drugs, healthcare use, and productivity
      losses were retrieved from nationwide registers, while EuroQol 5-Dimensions
      utility was collected quarterly. RESULTS: Of 487 patients initially enrolled, 128
      and 130 were randomised to infliximab and conventional treatment, respectively.
      The infliximab group accumulated higher drug and healthcare costs (?27,487 vs
      ?10,364; adjusted mean difference ?16,956 (95% CI 14,647 to 19,162)), while
      productivity losses did not differ (?33,804 vs ?29,220; ?3961 (95% CI -3986 to
      11,850)), resulting in higher societal cost compared to the conventional group
      (?61,291 vs ?39,584; ?20,916 (95% CI 12,800 to 28,660)). Mean accumulated quality
      adjusted life-years (QALYs) did not differ (1.10 vs 1.12; adjusted mean
      difference favouring infliximab treatment 0.01 (95% CI -0.07 to 0.08)). The
      incremental cost-effectiveness ratios for the infliximab versus conventional
      treatment strategy were ?2,404,197/QALY from the societal perspective and
      ?1,948,919/QALY from the healthcare perspective. CONCLUSIONS: In early,
      methotrexate-refractory rheumatoid arthritis, a treatment strategy commencing
      with addition of infliximab, as compared to sulfasalazine+hydroxychloroquine, was
      not cost-effective over 21 months at willingness to pay levels generally
      considered acceptable. TRIAL REGISTRATION NUMBER: NCT00764725.

PMID- 24737788
TI  - Long-term results after resection of bronchial carcinoid tumour: evaluation of
      survival and prognostic factors.
AB  - OBJECTIVES: We retrospectively analysed morbidity, mortality and oncological
      results of patients who had undergone surgery for bronchial carcinoid tumours.
      METHODS: Between 2002 and 2012, 65 patients with bronchial carcinoids underwent
      lobectomy (n = 34), sublobar resection (segmentectomy/wedge) (n = 18), sleeve
      lobectomy (n = 5) (reconstruction of the pulmonary artery was associated in 1
      case), sleeve resection of the main bronchus (n = 4) or pneumonectomy (n = 4)
      (reconstruction of the carina was associated in 1 case). RESULTS: Resection was
      radical with histologically negative margins in all patients (R0). Histology
      showed typical carcinoid (TC) in 55 (84.6%) patients and atypical carcinoid (AC)
      in 10 (15.4%) patients. Final pathological stages were Stage I in 42 (64.6%)
      patients, Stage II in 18 (27.7%) and Stage III in 5 (7.7%). No postoperative
      mortality was observed. The postoperative morbidity rate was 15.4% (no bronchial
      and/or vascular reconstructive-related complications occurred). The median follow
      up was 58 (range 2-121) months. The overall recurrence rate was 12.3% (n = 8).
      The survival rate at 5 years was 100% for TC and 87% for AC. Disease-free
      survival rates at 3 and 5 years were 95 and 93% for TC and 78 and 44% for AC,
      respectively (P = 0.004). Pathological nodal involvement (pN1-N2) did not affect
      overall survival or recurrence. CONCLUSIONS: The surgical treatment of bronchial
      carcinoids provides high long-term survival rates. Low postoperative morbidity
      and mortality can be expected even after bronchial reconstruction. The AC appears
      to be the main factor that determines the risk of recurrence. Bronchial
      reconstructive lung sparing operations are not related to an increased recurrence
      rate.

PMID- 24737789
TI  - Bleeding from the apex during transapical transcatheter aortic valve
      implantation: a simple solution by balloon occlusion of the apex.
AB  - Bleeding from the apex during transapical transcatheter aortic valve implantation
      is a potentially catastrophic event, which may seem at first sight to be an
      uncontrollable circumstance. We describe a simple 'trick' to control this problem
      that we used successfully in 5 patients. A Fogarty occlusion aortic catheter is
      gently inserted into the left ventricular cavity through the apical hole used for
      the transcatheter procedure, the balloon is slowly inflated with 10-15 ml of
      saline and the catheter is slightly pulled back 1 or 2 cm. This manoeuvre
      immediately stops the bleeding and enables safe suturing of the apex. 

PMID- 24737792
TI  - Hypermethylation of the GABRE~miR-452~miR-224 promoter in prostate cancer
      predicts biochemical recurrence after radical prostatectomy.
AB  - PURPOSE: Available tools for prostate cancer diagnosis and prognosis are
      suboptimal and novel biomarkers are urgently needed. Here, we investigated the
      regulation and biomarker potential of the GABRE~miR-452~miR-224 genomic locus.
      EXPERIMENTAL DESIGN: GABRE/miR-452/miR-224 transcriptional expression was
      quantified in 80 nonmalignant and 281 prostate cancer tissue samples. GABRE~miR
      452~miR-224 promoter methylation was determined by methylation-specific qPCR
      (MethyLight) in 35 nonmalignant, 293 prostate cancer [radical prostatectomy (RP)
      cohort 1] and 198 prostate cancer tissue samples (RP cohort 2).
      Diagnostic/prognostic biomarker potential of GABRE~miR-452~miR-224 methylation
      was evaluated by ROC, Kaplan-Meier, uni- and multivariate Cox regression
      analyses. Functional roles of miR-224 and miR-452 were investigated in PC3 and
      DU145 cells by viability, migration, and invasion assays and gene-set enrichment
      analysis (GSEA) of posttransfection transcriptional profiling data. RESULTS:
      GABRE~miR-452~miR-224 was significantly downregulated in prostate cancer compared
      with nonmalignant prostate tissue and had highly cancer-specific aberrant
      promoter hypermethylation (AUC = 0.98). Functional studies and GSEA suggested
      that miR-224 and miR-452 inhibit proliferation, migration, and invasion of PC3
      and DU145 cells by direct/indirect regulation of pathways related to the cell
      cycle and cellular adhesion and motility. Finally, in uni- and multivariate
      analyses, high GABRE~miR-452~miR-224 promoter methylation was significantly
      associated with biochemical recurrence in RP cohort 1, which was successfully
      validated in RP cohort 2. CONCLUSION: The GABRE~miR-452~miR-224 locus is
      downregulated and hypermethylated in prostate cancer and is a new promising
      epigenetic candidate biomarker for prostate cancer diagnosis and prognosis. Tumor
      suppressive functions of the intronic miR-224 and miR-452 were demonstrated in
      two prostate cancer cell lines, suggesting that epigenetic silencing of GABRE~miR
      452~miR-224 may be selected for in prostate cancer.

PMID- 24737793
TI  - Novosphingobium kunmingense sp. nov., isolated from a phosphate mine.
AB  - A yellow-pigmented, Gram-stain-negative, strictly aerobic, rod-shaped, round
      ended bacterium, designated strain 18-11HK(T), was isolated from a phosphate mine
      situated in the suburb of Kunming in Yunnan province in south-western China. The
      taxonomic status of this strain was evaluated by using a polyphasic approach. On
      the basis of 16S rRNA gene sequence similarity, strain 18-11HK(T) was shown to
      belong to the genus Novosphingobium, showing the highest levels of sequence
      similarity with respect to 'Novosphingobium ginsenosidimutans' FW-6 (97.2%),
      Novosphingobium subterraneum DSM 12447(T) (96.7%), Novosphingobium
      aromaticivorans DSM 12444(T) (96.7%) and Novosphingobium tardaugens DSM 16702(T)
      (96.3%). Strain 18-11HK(T) had a genomic DNA G+C content of 65.3 mol% and Q-10 as
      the predominant respiratory quinone. DNA-DNA hybridizations of strain 18-11HK(T)
      with N. subterraneum DSM 12447(T), N. aromaticivorans DSM 12444(T) and N.
      tardaugens DSM 16702(T) showed low relatedness values of 29.6, 33.5 and 32.3%,
      respectively. The predominant fatty acids of strain 18-11HK(T) were summed
      feature 8 (C18 : 1omega7c and/or C18: 1omega6c), summed feature 3 (C16 : 1omega7c
      and/or C16 : 1omega6c) and C16 : 0, and the major 2-hydroxy fatty acid was C14 :
      0 2-OH. The polar lipid profile revealed the presence of sphingoglycolipid,
      phosphatidylethanolamine, phosphatidylglycerol, diphosphatidylglycerol,
      phosphatidylcholine and some unidentified lipids. On the basis of its phenotypic
      properties and phylogenetic distinctiveness, strain 18-11HK(T) represents a novel
      species of the genus Novosphingobium, for which the name Novosphingobium
      kunmingense sp. nov. is proposed. The type strain is 18-11HK(T) ( = CGMCC
      1.12274(T) = DSM 25975(T)).

PMID- 24737794
TI  - Tomitella cavernea sp. nov., an actinomycete isolated from soil.
AB  - A Gram-staining-positive, aerobic, non-spore-forming, irregular rod-shaped
      actinobacterium, designated YIM C00895(T), was isolated from a soil sample
      collected from Jiuxiang Scenic Region, Yunnan province, south-west China. The
      strain was able to grow at 10-28  degrees C, pH 6.0-10.0 and 0-11% NaCl (w/v).
      Phylogenetic analysis based on 16S rRNA (95.3%) gene sequences revealed the
      highest similarity to Tomitella biformata AHU1821(T). The whole-cell hydrolysates
      of strain YIM C00895(T) contained meso-diaminopimelic acid, arabinose and
      galactose, indicating chemotype IV. The muramic acids in the peptidoglycan were
      glycolated. The polar lipids consisted of diphosphatidylglycerol,
      phosphatidylethanolamine, phosphatidylinositol, phosphatidylinositol mannosides
      and an unidentified glycolipid. MK-9(H2) was the predominant menaquinone. The
      major fatty acids were C14 : 0, C16 : 0, C16 : 1 and C18 : 1omega9c and
      tuberculostearic acid (10-methyl C18 : 0) was present in relatively small amounts
      (4.5%). TLC analysis of its cellular mycolic acids showed a similar profile to
      Tomitella biformata DSM 45403(T). The DNA G+C content of the strain was 67.5
      mol%. The results of physiological and biochemical tests allowed strain YIM
      C00895(T) to be differentiated phenotypically from Tomitella biformata DSM
      45403(T). On the basis of evidence from this polyphasic study, the novel species
      Tomitella cavernea sp. nov. is proposed. The type strain of Tomitella cavernea is
      YIM C00895(T) ( = DSM 45788(T)  = JCM 18542(T)).

PMID- 24737791
TI  - Molecular pathways: interleukin-15 signaling in health and in cancer.
AB  - Interleukin-15 (IL-15) is a proinflammatory cytokine involved in the development,
      survival, proliferation, and activation of multiple lymphocyte lineages utilizing
      a variety of signaling pathways. IL-15 utilizes three distinct receptor chains in
      at least two different combinations to signal and exert its effects on the immune
      system. The binding of IL-15 to its receptor complex activates an "immune
      enhancing" signaling cascade in natural killer cells and subsets of T cells, as
      well as the induction of a number of proto-oncogenes. Additional studies have
      explored the role of IL-15 in the development and progression of cancer, notably
      leukemia of large granular lymphocytes, cutaneous T-cell lymphoma, and multiple
      myeloma. This review provides an overview of the molecular events in the IL-15
      signaling pathway and the aberrancies in its regulation that are associated with
      chronic inflammation and cancer. We briefly explore the potential therapeutic
      opportunities that have arisen as a result of these studies to further the
      treatment of cancer. These involve both targeting the disruption of IL-15
      signaling as well as IL-15-mediated enhancement of innate and antigen-specific
      immunity.

PMID- 24737795
TI  - Classification and phylogeny of the cyanobiont Anabaena azollae Strasburger: an
      answered question?
AB  - The symbiosis Azolla-Anabaena azollae, with a worldwide distribution in
      pantropical and temperate regions, is one of the most studied, because of its
      potential application as a biofertilizer, especially in rice fields, but also as
      an animal food and in phytoremediation. The cyanobiont is a filamentous,
      heterocystic cyanobacterium that inhabits the foliar cavities of the pteridophyte
      and the indusium on the megasporocarp (female reproductive structure). The
      classification and phylogeny of the cyanobiont is very controversial: from its
      morphology, it has been named Nostoc azollae, Anabaena azollae, Anabaena
      variabilis status azollae and recently Trichormus azollae, but, from its 16S rRNA
      gene sequence, it has been assigned to Nostoc and/or Anabaena, and from its
      phycocyanin gene sequence, it has been assigned as non-Nostoc and non-Anabaena.
      The literature also points to a possible co-evolution between the cyanobiont and
      the Azolla host, since dendrograms and phylogenetic trees of fatty acids, short
      tandemly repeated repetitive (STRR) analysis and restriction fragment length
      polymorphism (RFLP) analysis of nif genes and the 16S rRNA gene give a two
      cluster association that matches the two-section ranking of the host (Azolla).
      Another controversy surrounds the possible existence of more than one genus or
      more than one species strain. The use of freshly isolated or cultured cyanobionts
      is an additional problem, since their morphology and protein profiles are
      different. This review gives an overview of how morphological, chemical and
      genetic analyses influence the classification and phylogeny of the cyanobiont and
      future research. 

PMID- 24737796
TI  - The quality of police data on RTC fatalities in India.
AB  - BACKGROUND: Police records are the major source of data on road traffic collision
      (RTC) deaths in India. OBJECTIVE: To examine the utility and quality of police
      data on RTC deaths available from two sources. METHODS: Police data on RTC deaths
      available from National Crime Records Bureau (NCRB) and Ministry of Road
      Transport and Highways (MoRTH) were accessed. The utility of these data for
      surveillance and consistency of data reported by the two organisations was
      examined. Data completeness was assessed for India, its six geographic regions
      and for the mode of travel using cause of death estimates from the Sample
      Registration System (SRS) and Global Burden of Disease (GBD) as a reference.
      RESULTS: Data imperative for surveillance including deaths by age and sex for
      each state, the counterpart vehicle or object and use of safety equipment were
      not available. The total number of deaths reported by NCRB and MoRTH was similar
      across states but showed large differences by mode of travel categories. Compared
      with GBD, completeness of the number of fatalities reported by both sources in
      2010 was approximately 50%. Completeness for the geographic regions ranged from
      26.4% to 76.4%, using SRS data, in 2001-2003. CONCLUSIONS: This detailed
      examination of police data on RTC fatalities from two sources has raised several
      questions about the validity of these data and has highlighted a number of gaps
      that limit the usefulness of these data for surveillance and informing road
      safety policies. Unless these are addressed, significant reductions in RTC
      fatalities cannot be achieved in India.

PMID- 24737797
TI  - The Affordable Care Act's Medicaid expansion creates incentive for state Medicaid
      agencies to provide reimbursement for hospital-based violence intervention
      programmes.

PMID- 24737798
TI  - A role for lactate dehydrogenases in the survival of Neisseria gonorrhoeae in
      human polymorphonuclear leukocytes and cervical epithelial cells.
AB  - Lactate is an abundant metabolite, produced by host tissues and commensal
      organisms, and it represents an important potential carbon source for bacterial
      pathogens. In the case of Neisseria spp., the importance of the lactate permease
      in colonization of the host has been demonstrated, but there have been few
      studies of lactate metabolism in pathogenic Neisseria in the postgenomic era. We
      describe herein the characterization of genome-annotated, respiratory, and
      substrate-level lactate dehydrogenases (LDHs) from the obligate human pathogen
      Neisseria gonorrhoeae. Biochemical assays using N. gonorrhoeae 1291 wild type and
      isogenic mutant strains showed that cytoplasmic LdhA (NAD(+)-dependent D-lactate
      dehydrogenase) and the membrane-bound respiratory enzymes, LdhD (D-lactate
      dehydrogenase) and LldD (L-lactate dehydrogenase) are correctly annotated.
      Mutants lacking LdhA and LdhD showed greatly reduced survival in neutrophils
      compared with wild type cells, highlighting the importance of D-lactate
      metabolism in gonococcal survival. Furthermore, an assay of host colonization
      using the well-established human primary cervical epithelial cell model revealed
      that the two respiratory enzymes make a significant contribution to colonization
      of and survival within the microaerobic environment of the host. Taken together,
      these data suggest that host-derived lactate is critical for the growth and
      survival of N. gonorrhoeae in human cells. 

PMID- 24737799
TI  - HLA and killer cell immunoglobulin-like receptors influence the natural course of
      CMV infection.
AB  - BACKGROUND: Natural killer (NK) cells provide a major defense against
      cytomegalovirus (CMV) infection through the interaction of their surface
      receptors, including the activating and inhibitory killer immunoglobulin-like
      receptors (KIRs), and human leukocyte antigens (HLA) class I molecules. This
      study assessed whether the KIR and HLA repertoire may influence the risk of
      developing symptomatic or asymptomatic disease after primary CMV infection in the
      immunocompetent host. METHODS: Sixty immunocompetent patients with primary
      symptomatic CMV infection were genotyped for KIR and their HLA ligands, along
      with 60 subjects with a previous asymptomatic infection as controls. RESULTS: The
      frequency of the homozygous A haplotype (only KIR2DS4 as activating KIR) was
      higher in symptomatic patients than controls (30% vs 12%, respectively; odds
      ratio [OR] = 3.24; P = .01). By logistic regression, the risk of developing
      symptomatic disease was associated with the homozygous A haplotype and the
      HLABw4(T) allele. Combining the 2 independent variables, we found that 37 out of
      60 (62%) symptomatic patients but only 18 out of 60 (30%) of controls possessed
      the homozygous A haplotype or the HLABw4(T) allele with a highly significant OR
      (OR = 3.75, P < .0005). CONCLUSIONS: Immunocompetent subjects carrying the
      homozygous A haplotype or the HLABw4(T) allele are at higher risk of developing
      symptomatic disease after primary CMV infection.

PMID- 24737800
TI  - Human alpha-amylase present in lower-genital-tract mucosal fluid processes
      glycogen to support vaginal colonization by Lactobacillus.
AB  - Lactobacillus colonization of the lower female genital tract provides protection
      from the acquisition of sexually transmitted diseases, including human
      immunodeficiency virus, and from adverse pregnancy outcomes. While glycogen in
      vaginal epithelium is thought to support Lactobacillus colonization in vivo, many
      Lactobacillus isolates cannot utilize glycogen in vitro. This study investigated
      how glycogen could be utilized by vaginal lactobacilli in the genital tract.
      Several Lactobacillus isolates were confirmed to not grow in glycogen, but did
      grow in glycogen-breakdown products, including maltose, maltotriose,
      maltopentaose, maltodextrins, and glycogen treated with salivary alpha-amylase. A
      temperature-dependent glycogen-degrading activity was detected in genital fluids
      that correlated with levels of alpha-amylase. Treatment of glycogen with genital
      fluids resulted in production of maltose, maltotriose, and maltotetraose, the
      major products of alpha-amylase digestion. These studies show that human alpha
      amylase is present in the female lower genital tract and elucidates how
      epithelial glycogen can support Lactobacillus colonization in the genital tract. 

PMID- 24737802
TI  - Filarial antigens mediate apoptosis of human monocytes through Toll-like receptor
      4.
AB  - BACKGROUND: Apoptosis of several host cells induced by parasites/parasite
      products has been investigated in human filariasis to understand immune
      hyporesponsiveness. However, apoptosis of monocytes-one of the major antigen
      presenting cells in peripheral circulation, which are chronically exposed to
      filarial antigens in infected subjects-is yet to be understood. METHODS:
      Apoptosis of human monocytes with Brugia pahangi antigen (BpA) was demonstrated
      by scoring several apoptotic markers using flow cytometry. Ability of BpA and
      plasma of infected subjects to suppress lymphocyte proliferation was demonstrated
      by (3)H thymidine incorporation assay and carboxyfluorescein succinimidyl ester
      dilution assay. RESULTS: BpA induced significant apoptosis of normal human
      monocytes, primarily through Toll-like receptor 4 (TLR4), and suppressed
      phytohemagglutinin (PHA)-mediated proliferation of normal human T lymphocytes.
      However, monocytes of Wuchereria bancrofti-infected subjects were resistant to
      BpA-induced apoptosis. Plasma of infected subjects also mediated apoptosis of
      normal monocytes, presumably due to circulating filarial antigens, and resulted
      in inhibition of PHA-induced proliferation. CONCLUSION: Normal human monocytes
      were found to be qualitatively different from those of filariasis-infected
      subjects; whereas filarial antigens mediate apoptosis of normal human monocytes
      through TLR4, those of infected subjects were found to be resistant.

PMID- 24737801
TI  - Estimation of recent and long-term malaria transmission in a population by
      antibody testing to multiple Plasmodium falciparum antigens.
AB  - BACKGROUND: Tools that estimate recent and long-term malaria transmission in a
      population would be highly useful for malaria elimination programs. METHODS: The
      prevalence of antibodies to 11 Plasmodium falciparum antigens was assessed by
      cytometric bead assay or enzyme-linked immunosorbent assay in 1000 people in a
      highland area of Kenya over 14 months, during a period of interrupted malaria
      transmission. RESULTS: Antibodies differed by antigen in acquisition with age:
      rapid (>80% antibody positive by age 20 years, 5 antigens), moderate (>40%
      positive by age 20 years, 3 antigens), or slow (<40% positive by age 20 years, 3
      antigens). Antibody seroreversion rates in the 14 months between samples
      decreased with age rapidly (7 antigens), slowly (3 antigens), or remained high at
      all ages (schizont extract). Estimated antibody half-lives in individuals >10
      years of age were long (40 to >80 years) for 5 antigens, moderate (5-20 years)
      for 3 antigens, and short (<1 year) for 3 antigens. CONCLUSIONS: Antibodies to P.
      falciparum antigens in malaria-endemic areas vary by age, antigen, and time since
      last exposure to P. falciparum. Multiplex P. falciparum antibody testing could
      provide estimates of long-term and recent malaria transmission and potentially of
      a population's susceptibility to future clinical malaria.

PMID- 24737803
TI  - Low uptake of Pap smear testing among medical clinic attendees in a tertiary care
      hospital in Sri Lanka.
AB  - INTRODUCTION: The Papanicolaou (Pap) smear test is a safe and effective screening
      test for pre-invasive cervical cancer. The test is offered free of charge through
      well-woman clinics in Sri Lanka, but previous studies have shown poor awareness
      and uptake. METHODS: We used an interviewer administered validated questionnaire
      to conduct a cross sectional survey among ever-married women between the ages of
      25 and 65 years attending a medical clinic at the National Hospital of Sri Lanka.
      We obtained data on socio-demographic characteristics, awareness/knowledge and
      uptake status of Pap smear testing. RESULTS: A total of 188/280 eligible women
      were interviewed (67.1%). Participant ages ranged from 29-65 years. Awareness
      about Pap smear testing was found in 111 (59.0%) women of whom 41 (36.9%) did not
      know that the Pap smear was used to detect pre-cancerous lesions. Only 34 (18.1%)
      subjects had ever had a Pap smear taken. Univariate associations related to Pap
      smear uptake were: prior awareness of the test (p<0.001), higher parity
      (p=0.022), and knowing someone with cervical carcinoma (p<0.001). Multivariate
      regression analysis confirmed the same as independent associations of test uptake
      (p<0.001, p=0.012, p=0.013 respectively). CONCLUSIONS: Knowledge regarding Pap
      smear testing was poor. Pap smear uptake was very low, and did not parallel prior
      knowledge, although knowledge did influence uptake. Parity and contact with
      patients with cervical cancer correlated with uptake. There is an urgent need to
      increase uptake through a multi-pronged campaign.

PMID- 24737804
TI  - Effective T helper cell responses against retroviruses: are all clonotypes equal?
AB  - The critical importance of CD4(+) T cells in coordinating innate and adaptive
      immune responses is evidenced by the susceptibility to various pathogenic and
      opportunistic infections that arises from primary or acquired CD4(+) T cell
      immunodeficiency, such as following HIV-1 infection. However, despite the clearly
      defined roles of cytotoxic CD8(+) T cells and antibodies in host protection from
      retroviruses, the ability of CD4(+) T cells to exert a similar function remains
      unclear. Recent studies in various settings have drawn attention to the
      complexity of the T cell response within and between individuals. Distinct TCR
      clonotypes within an individual differ substantially in their response to the
      same epitope. Functionally similar, "public" TCR clonotypes can also dominate the
      response of different individuals. TCR affinity for antigen directly influences
      expansion and differentiation of responding T cells, also likely affecting their
      ultimate protective capacity. With this increasing understanding of the
      parameters that determine the magnitude and effector type of the T cell response,
      we are now better equipped to address the protective capacity against
      retroviruses of CD4(+) T cell clonotypes induced by natural infection or
      vaccination. 

PMID- 24737808
TI  - [Health Impact Assessments (HIA): an intersectoral process for action on the
      social, economic and environmental determinants of health].
AB  - Health Impact Assessment (HIA) is a practice that has grown in popularity
      worldwide, since the end of the 1990s. Originally used in the framework of
      Environmental Impact Assessments (EIAs), HIA has become enriched through the
      addition of knowledge and principles based on the social determinants of health
      and the tackling of health inequalities, and has been brought to bear on the
      policy-planning process at all levels of government. HIA has three overlapping
      objectives: to assess the potential effects of a policy on health, to encourage
      citizen and stakeholder participation in the impact analysis process, and to
      inform the decision-making process. This article briefly defines HIA; defines its
      standardized process in successive steps, which allows users to give structure to
      their actions and to establish the steps to be followed (detection, framing,
      analysis, recommendations and evaluation); and offers three examples of HIA in
      three different situations: the Geneva canton of Switzerland; Rennes, France; and
      in the Monteregie region of Quebec, Canada. Together, these illustrations show
      that HIA is a promising strategy to influence local decisions and to integrate
      health into projects and policies at the local and regional levels.

PMID- 24737809
TI  - [Health and social information systems in support of local health planning:
      issues and challenges].
AB  - Health information is indispensable for monitoring the progress that has been
      made in improving and maintaining population health and health system functions.
      In the context of health reforms aiming to bring health systems closer to
      populations and with the objective of consistent health services planning at the
      community level, access to reliable social and health data has become a major
      issue. The need to develop specific treatment tools and the appropriation of
      results by the various actors involved (decision makers, planners, researchers
      and consumers) are central to the presentations and exchanges in this symposium.

PMID- 24737805
TI  - Circulating adiponectin and breast cancer risk: a systematic review and meta
      analysis.
AB  - BACKGROUND: We conducted a meta-analysis in order to investigate whether
      circulating adiponectin, an insulin-sensitizing hormone produced by adipocytes,
      is associated with breast cancer risk. METHODS: A systematic literature search
      was performed in PubMed, Medline, EMBASE, ISI Web of Knowledge and the Cochrane
      Library. The summary relative risk (SRR) was calculated by pooling the different
      study-specific estimates using the random effect models. Meta-regression,
      subgroup and sensitivity analyses were carried out to investigate between-study
      heterogeneity and to test publication bias. RESULTS: Data from 15 observational
      studies, published between 2003 and April 2013 for a total of 4249 breast cancer
      cases, were analysed. The SRR for the 'highest' vs 'lowest' adiponectin levels
      indicated a 34% reduction in breast cancer risk [95% confidence interval (CI):
      13%-50%]. Between-study heterogeneity was not substantial (I(2)=53%). Ten studies
      were included in the dose-response analysis: the SRR for an increase of 3 ug/ml
      of adiponectin corresponded to a 5% risk reduction (95% CI: 1%-9%). The
      comparison between 'highest' and 'lowest' levels of adiponectin showed an inverse
      association in postmenopausal women (SRR=0.80; 95% CI: 0.63-1.01) and an
      indication of an inverse relationship in premenopausal women (SRR=0.72, 95% CI:
      0.30-1.72). No evidence of publication bias was found. CONCLUSIONS: Low
      circulating adiponectin levels are associated with an increased breast cancer
      risk. However, properly designed studies are needed to confirm the role of
      adiponectin as breast cancer biomarker, and clinical trials should be performed
      to identify those interventions that may be effective in modulating adiponectin
      levels and reducing breast cancer risk.

PMID- 24737810
TI  - [The co-construction of change in community health service provision in Senegal].
AB  - An experience of collaboration between researchers and the Ministry of Health of
      Senegal has encouraged the social uses of results from research on the health of
      communities. This article presents the contributions of partnership-based
      research to tackling health inequalities. Following a diagnostic shared with all
      the actors (practitioners and users) that allowed us to identify the reasons
      behind the under-utilization of well-equipped and renovated health
      establishments, three innovations were implemented: district surgery,
      complementary health insurance and flat-rate fees. In the four central regions of
      Senegal where this experiment was launched, the research that was carried out
      allowed for a better comprehension of the processes and challenges in 'co
      constructing' knowledge between practitioners and researchers, in the context of
      relatively low access to healthcare. This article highlights the importance of
      this co-construction in encouraging concerted efforts to make relevant changes
      for improved, more equitable and more accessible local health services for
      communities.

PMID- 24737811
TI  - [Why must we 'master' trust between all parties, in order to cultivate a process
      of sustainable local development?].
AB  - A sustainable territorial development process represents a society characterized
      by its uniqueness to the territory of implementation. This notion of territory
      constitutes a fact of human nature, the development of which integrates
      collective and individual wellbeing through an intersectoral and
      multidisciplinary process. When carrying out joint projects, the partnership
      dynamic can transform interpersonal relationships and encourage the development
      of trust at the very core of the sustainable local development process. This
      trust enables the creation of a collective territorial intelligence, based on
      individual and sectoral knowledge and on know-how that form a shared, intangible
      heritage for each of the stakeholders in the sustainable territorial development
      process; however, as a fact of human nature, this trust remains fragile.

PMID- 24737812
TI  - [Supporting local communities in their actions for children living in a situation
      of poverty].
AB  - Avenir d'Enfants [Future of Children] emerged from a partnership between the
      government of Quebec and the Lucie and Andre Chagnon Foundation. The organization
      aims to provide local communities with resources, in order to support synergy
      between the principal early childhood organizations: childcare services,
      healthcare services, schools, family community organizations and municipalities.
      This article presents the context in which Avenir d'Enfants came into being,
      explains how the organization helps create the right conditions for local and
      regional initiatives to have an impact on the development of children living in a
      situation of poverty, and presents the challenges and success factors of this
      approach.

PMID- 24737814
TI  - [Local actions in health: from healthy city workshops to local health contracts].
AB  - After 10 years of partnership with the main towns within the department of
      Bouches du Rhone, France, in order to develop 'ateliers sante ville' [healthy
      city workshops], the department's territorial delegation for the regional health
      agency of Provence Alpes Cote d'Azur set up a 'contrats locaux de sante' (CLS)
      [local health contracts] scheme, with the goal of shifting from a local health
      programming and planning process to a cross-cutting process involving all of the
      related fields in health. The healthy city workshops, through 10 years of working
      together with towns, enabled the establishment of habits of partnership for joint
      processes, as well as a solid level of knowledge of the field of prevention. The
      transition to a more cross-cutting approach involving all health-related fields
      will be facilitated by this rich shared experience. The CLS is both a challenge
      for regional health agencies and a tangible manifestation of the new concept of
      'animation territoriale' [grass-roots programming].

PMID- 24737813
TI  - [Immigrant health in Canada: current state of knowledge, interventions and
      issues].
AB  - This article presents a synthesis of current research, presented during a
      symposium entitled, 'Immigrant health in Canada: Current state of knowledge,
      interventions and issues,' organized by the Public Health Agency of Canada. We
      begin with a general overview of the health of immigrants in Canada. We then
      analyze the role of community health workers in tackling health inequalities in
      this population, and certain ways of adapting health services to respond to the
      growing linguistic and cultural diversity present in Canadian society. We
      conclude with a discussion of one initiative developed by elderly-friendly local
      authorities. Throughout the symposium, the speakers emphasized an approach based
      on the determinants of health, which aims to improve health outcomes of the
      targeted populations, provide appropriate services and reduce health
      inequalities.

PMID- 24737815
TI  - [Citizens: allies of the health system].
AB  - Many international declarations recognize citizen participation as an important
      driver of success for health policy; however, in most countries the
      implementation of this principle has been delayed. Yet well-known phenomena, like
      ageing and incurred costs, should motivate decision makers to rely more on
      citizens and make them allies of the system, giving them power and
      responsibility. Citizens can first exercise this responsibility within the areas
      of prevention and health promotion. This responsibility then expands to include
      mutual assistance between community members. It is called upon in the definition
      of new social norms. It is recognized by the participation of citizens in health
      care decision-making bodies. Lastly, this responsibility applies when the time
      comes to choose which health services will be covered by the public system and
      which will be sent on to private insurers. The reasons to create a space for
      citizens are many. The methods to do it exist. What is needed is political
      willpower and means.

PMID- 24737816
TI  - [Health data at local and regional levels: what methods? What benefits for
      action?].
AB  - Health data can play a role in health promotion programs either to inform
      interventions or to raise awareness among health decision makers in their
      locality. Different tools are available to disseminate health data. Overviews
      present a snapshot of the social and health situation of a population. They can
      be carried out at different scales: regional, provincial, municipal or across
      borders, as was the case in the program 'Generations en Sante' [Generations in
      Health], which covered the French regions of Champagne-Ardenne, Picardie and Nord
      Pas-de-Calais; and the Belgian provinces of Luxembourg, Namur and Hainaut. The
      use of quantitative data encountered two obstacles: between-country comparability
      on the cross-border level and statistical fluctuation for small populations at
      the municipal level. Qualitative studies complement statistical data and refine
      one's knowledge of a situation. They can also enable the inclusion of a
      participative process.

PMID- 24737817
TI  - [Partnership-based research as a space to support innovation].
AB  - The process of joint evaluation involving several actors is criss-crossed by a
      process of negotiation and adjustment between different concerns,
      responsibilities and interests. How can we encourage a dialogue between knowledge
      from expertise and knowledge from experience, in order to produce knowledge that
      is scientifically based and useful for those who are involved in the programs?
      Far from being a mechanical process, this involves the delicate task of striking
      a balance, which relies on a negotiated partnership framework. The implementation
      of an advisory committee, organized by an interface function between the
      stakeholders of the intervention under study, has increasingly become recognized
      as a necessary condition for success in partnership-based research. These
      conditions enable the deployment of a reflexive system that can support social
      innovation--when the formulation of the problem and its resulting actions become
      enriched, as knowledge about the intervention develops.

PMID- 24737818
TI  - [Evaluation of public health plans: a driver of change for regional health policy
      in France?].
AB  - Between 2007-2010, each French region carried out an evaluation of their public
      health plan, at the very moment when regional health system governance reform was
      taking place. The objective of this article is to analyze the influence of this
      dynamic of evaluation on health policy at the regional and national levels. An in
      depth analysis in nine regions showed short-term consequences that were
      inconsistent among regions, depending on the implementation schedule and the
      evaluation process that was put into place. On the other hand, the lessons that
      emerged reinforced local expertise that was useful for the new planning exercise.
      This regional work has not yet been taken up nationally, but we cannot exclude
      the possibility that it fueled discussions in the working groups preparing the
      reform.

PMID- 24737819
TI  - [Healthy ageing in a linguistic minority situation in Canada: issues, challenges
      and collective mobilization].
AB  - In Canada, the health of both French and English speakers living in linguistic
      minority situations is a subject of interest to several researchers and community
      organizations. This article draws upon a symposium on the theme of healthy ageing
      in a linguistic minority situation, presented at the 4th International Colloquium
      for Local and Regional Health Programmes. Three aspects are presented: the
      identification of factors associated with perceived health, home care and
      malnutrition screening. The results describe: (a) The determinants of perceived
      health, such as health care services, the vitality of the minority community and
      education; (b) The lack of changes to home care services, despite the ageing of
      the population; and (c) The high prevalence of malnutrition among the elderly in
      New Brunswick, Canada. Finally, we make suggestions regarding the design and
      implementation of a national policy on ageing in Canada, in order to ensure high
      quality services along the entire health continuum.

PMID- 24737821
TI  - Introduction.

PMID- 24737820
TI  - [The architects of change: a plenary session exchange].
AB  - The closing plenary of the colloquium was an occasion for exchange between the
      four panelists and the participants. The panelists included Luc Berghmans, a
      doctor and director of the regional health observatory of Hainaut, Belgium;
      Louise Bouchard, a sociologist and professor in the Sociology and Anthropology
      Department, University of Ottawa, Canada; Michel O'Neill, a sociologist and
      professor at the Faculty of Nursing Sciences, Laval University, Quebec City,
      Canada; and Philippe Lorenzo, director general of IREPS, the regional bureau for
      health education and promotion of Picardie in Amiens, France. Louise Potvin, who
      moderated the plenary, provides the summary that follows. During the colloquium,
      three main questions were debated: 1. At what point should health be placed at
      the forefront of local actions, if we wish to promote the values of equity? 2.
      How should actions at the local, regional, national and global levels be
      organized and articulated? Who are the partners, and what forms of governance
      need to be put into place? 3. What are the parameters needed in order to define
      the roles, tasks and competencies of the implementers of local and regional
      health programs, the architects of change? Each panelist had to respond to two
      out of the three questions. We report on the answers that panelists gave to these
      questions. As it is impossible to verify the exactitude of information given by
      audience members in support of their viewpoints, only the content of the remarks
      is given, without mentioning the examples that were provided.

PMID- 24737822
TI  - Governance for health, wellbeing and sustainability--what is at stake.

PMID- 24737826
TI  - Diagnostic criteria for constitutional mismatch repair deficiency syndrome:
      suggestions of the European consortium 'care for CMMRD' (C4CMMRD).
AB  - Constitutional mismatch repair deficiency (CMMRD) syndrome is a distinct
      childhood cancer predisposition syndrome that results from biallelic germline
      mutations in one of the four MMR genes, MLH1, MSH2, MSH6 or PMS2. The tumour
      spectrum is very broad, including mainly haematological, brain and intestinal
      tract tumours. Patients show a variety of non-malignant features that are
      indicative of CMMRD. However, currently no criteria that should entail diagnostic
      evaluation of CMMRD exist. We present a three-point scoring system for the
      suspected diagnosis CMMRD in a paediatric/young adult cancer patient. Tumours
      highly specific for CMMRD syndrome are assigned three points, malignancies
      overrepresented in CMMRD two points and all other malignancies one point.
      According to their specificity for CMMRD and their frequency in the general
      population, additional features are weighted with 1-2 points. They include
      multiple hyperpigmented and hypopigmented skin areas, brain malformations,
      pilomatricomas, a second childhood malignancy, a Lynch syndrome (LS)-associated
      tumour in a relative and parental consanguinity. According to the scoring system,
      CMMRD should be suspected in any cancer patient who reaches a minimum of three
      points by adding the points of the malignancy and the additional features. The
      diagnostic steps to confirm or refute the suspected diagnosis are outlined. We
      expect that application of the suggested strategy for CMMRD diagnosis will
      increase the number of patients being identified at the time when they develop
      their first tumour. This will allow adjustment of the treatment modalities,
      offering surveillance strategies for second malignancies and appropriate
      counselling of the entire family. 

PMID- 24737827
TI  - A missense mutation in the splicing factor gene DHX38 is associated with early
      onset retinitis pigmentosa with macular coloboma.
AB  - BACKGROUND: Retinitis pigmentosa (RP) is the most frequent inherited retinal
      disease, which shows a relatively high incidence of the autosomal-recessive form
      in Pakistan. METHODS: Genome-wide high-density single-nucleotide polymorphism
      (SNP) microarrays were used to identify homozygous regions shared by affected
      individuals of one consanguineous family. DNA of three affected and two healthy
      siblings was used for SNP genotyping. Genotyping data were then analysed by
      Homozygosity Mapper. DNA of the proband was further analysed employing exome
      sequencing. RESULTS: Homozygosity mapping revealed a single homozygous region on
      chromosome 16, shared by three affected individuals. Subsequent exome sequencing
      identified a novel missense mutation, c.995G>A; p.(Gly332Asp), in DHX38. This
      mutation was found to be present in a homozygous state in four affected
      individuals while two healthy siblings and the parents of the affected persons
      were heterozygous for this mutation. This variant thereby yields a logarithm of
      the odds (LOD) score of 3.25, which is highly suggestive for linkage. This
      variant was neither detected in 180 ethnically matched control individuals, nor
      in 7540 Africans or Caucasians and an in-house database that contained the exome
      data of 400 individuals. CONCLUSIONS: By combining genome-wide homozygosity
      mapping and exome sequencing, a novel missense mutation was identified in the
      DHX38 gene that encodes the pre-mRNA splicing factor PRP16, in a Pakistani family
      with early-onset autosomal-recessive RP. The phenotype is different from those
      associated with other retinal pre-mRNA splicing factors and DHX38 is the first
      pre-mRNA splicing gene that is putatively associated with autosomal-recessive
      inherited RP.

PMID- 24737828
TI  - Sexual Offenders' Perceptions of the Client-Therapist Relationship: The Role of
      Risk.
AB  - The therapeutic alliance has been shown to be integral to treatment outcomes even
      in forensic settings. There is still a relative dearth of research examining
      factors related to the formation of the therapeutic alliance in sex offender
      treatment specifically. Using a sample of 202 incarcerated male sexual offenders
      participating in sex offender treatment, this study examined whether perceptions
      of the client-therapist relationship from the perspective of male sexual
      offenders varied by risk for sexual and general recidivism. Overall, we found a
      significant negative relationship between risk for sexual recidivism and bond
      formation. However, when therapist subscale scores on the Working Alliance
      Inventory were considered by therapist gender, higher risk sexual offenders
      perceived poorer bonds with their female therapists, relative to their male
      therapists. Findings are discussed as they pertain to therapeutic relationships
      and responsivity issues in sex offender treatment. 

PMID- 24737829
TI  - Keep testing the waters: Fanniff and Letourneau reply.
AB  - Hecker raises a number of important considerations in interpreting the review of
      literature and empirical research presented in Fanniff and Letourneau's article
      "Another Piece of the Puzzle: Psychometric Properties of the J-SOAP-II." Despite
      these considerations and the publication of new research in the interim, the
      current authors continue to urge caution in the interpretation of Juvenile Sex
      Offender Assessment Protocol-II (J-SOAP-II) scores in disposition evaluations,
      largely due to the serious consequences that youth face in this context. 

PMID- 24737830
TI  - Impact of local strain on Ti-L2,3 electron energy-loss near-edge structures of
      BaTiO3: a first-principles multiplet study.
AB  - Identification of local strains is crucial because the local strains largely
      influence the ferroelectric property of BaTiO3. The effects of local strains
      induced by external pressures on the Ti-L2,3 electron energy-loss near-edge
      structure (ELNES) of BaTiO3 were theoretically investigated using first
      principles multiplet calculations. We revealed that the effects appear in the
      position of the spectral threshold, namely the spectrum shifts to lower and
      higher energy sides by the tensile and compressive pressures, respectively. We
      concluded that conventional ELNES observations can identify only large strains
      induced by -10 GPa, and 0.1 eV energy resolution is required to identify +/-2% of
      strains.

PMID- 24737831
TI  - Health service accreditation reinforces a mindset of high-performance human
      resource management: lessons from an Australian study.
AB  - OBJECTIVE: To investigate whether an accreditation program facilitates healthcare
      organizations (HCOs) to evolve and maintain high-performance human resource
      management (HRM) systems. DESIGN: Cross-sectional multimethod study. SETTING AND
      PARTICIPANTS: Healthcare organizations participating in the Australian Council on
      Healthcare Standards Evaluation and Quality Improvement Program (EQuIP 4) between
      2007 and 2011. MAIN OUTCOME MEASURES: Ratings across the EQuIP 4 HRM criteria, a
      clinical performance measure, surveyor reports (HRM information) and interview
      data (opinions and experiences regarding HRM and accreditation). RESULTS:
      Healthcare organizations identified as high performing on accreditation HRM
      criteria seek excellence primarily because of internal motivations linked to best
      practice. Participation in an accreditation program is a secondary and less
      significant influence. Notwithstanding, the accreditation program provides the
      HCO opportunity for internal and external review and assessment of their
      performance; the accreditation activities are reflective learning and feedback
      events. CONCLUSIONS: This study reveals that HCOs that pursue highly performing
      HRM systems use participation in an accreditation program as an opportunity.
      Their organizational mindset is to use the program as a tool by which to reflect
      and obtain feedback on their performance so to maintain or improve their
      management of staff and delivery of care.

PMID- 24737832
TI  - Does public reporting improve the quality of hospital care for acute myocardial
      infarction? Results from a regional outcome evaluation program in Italy.
AB  - OBJECTIVE: To evaluate whether public reporting of performance data was
      associated with a change over time in quality indicators for acute myocardial
      infarction (AMI) in Italian hospitals. DESIGN: Pre-post evaluation of AMI
      indicators in the Lazio region, before and after disclosure of the Regional
      Outcome Evaluation Program, and a comparative evaluation versus other Italian
      regions not participating in the program. SETTING/DATA SOURCES: Nationwide
      Hospital Information System and vital status records. PARTICIPANTS: 24 800
      patients treated for AMI in Lazio and 39 350 in the other regions. INTERVENTION:
      Public reporting of the Regional Outcome Evaluation Program in the Lazio region.
      MAIN OUTCOME MEASURE: Risk-adjusted indicators for AMI. RESULTS: The proportion
      of ST-segment elevation myocardial infarction (STEMI) patients treated with
      percutaneous coronary interventions (PCI) within 48 h in Lazio changed from 31.3
      to 48.7%, before and after public reporting, respectively (relative increase 56%;
      P < 0.001). In the other regions, the proportion increased from 51.5 to 58.4%
      (relative increase 13%; P < 0.001). Overall 30-day mortality and 30-day mortality
      for patients treated with PCI did not improve during the study period. The 30-day
      mortality for STEMI patients not treated with PCI in Lazio was significantly
      higher in 2009 (29.0%) versus 2006/07 (24.0%) (P = .002). CONCLUSIONS: Public
      reporting may have contributed to increasing the proportion of STEMI patients
      treated with timely PCI. The mortality outcomes should be interpreted with
      caution. Changes in AMI diagnostic and coding systems should also be considered.
      Risk-adjusted quality indicators represent a fundamental instrument for
      monitoring and potentially enhancing quality of care.

PMID- 24737833
TI  - PACIC Instrument: disentangling dimensions using published validation models.
AB  - OBJECTIVE: To better understand the structure of the Patient Assessment of
      Chronic Illness Care (PACIC) instrument. More specifically to test all published
      validation models, using one single data set and appropriate statistical tools.
      DESIGN: Validation study using data from cross-sectional survey. PARTICIPANTS: A
      population-based sample of non-institutionalized adults with diabetes residing in
      Switzerland (canton of Vaud). MAIN OUTCOME MEASURE: French version of the 20
      items PACIC instrument (5-point response scale). We conducted validation analyses
      using confirmatory factor analysis (CFA). The original five-dimension model and
      other published models were tested with three types of CFA: based on (i) a
      Pearson estimator of variance-covariance matrix, (ii) a polychoric correlation
      matrix and (iii) a likelihood estimation with a multinomial distribution for the
      manifest variables. All models were assessed using loadings and goodness-of-fit
      measures. RESULTS: The analytical sample included 406 patients. Mean age was 64.4
      years and 59% were men. Median of item responses varied between 1 and 4 (range 1
      5), and range of missing values was between 5.7 and 12.3%. Strong floor and
      ceiling effects were present. Even though loadings of the tested models were
      relatively high, the only model showing acceptable fit was the 11-item single
      dimension model. PACIC was associated with the expected variables of the field.
      CONCLUSIONS: Our results showed that the model considering 11 items in a single
      dimension exhibited the best fit for our data. A single score, in complement to
      the consideration of single-item results, might be used instead of the five
      dimensions usually described.

PMID- 24737834
TI  - Derivation and validation of a formula to estimate risk for 30-day readmission in
      medical patients.
AB  - OBJECTIVE: To create a simple readmission risk-prediction tool that can be
      generated easily at the bedside by physicians, nurses, care coordinators and
      discharge planners. DESIGN: Retrospective cohort study. SETTING: Tertiary
      academic medical center. PARTICIPANTS: Inpatients aged 18 and older on general
      internal medicine services. MEASURES: Predictor variables included age, prior
      hospitalization, high-risk diagnoses, high-risk medications, polypharmacy,
      depression, use of palliative care and a cumulative score summing these factors
      (readmission risk score-RRS). The main outcome measure was 30-day readmission.
      Predictive values were calculated. RESULTS: Readmission increased linearly from
      4.9% of those whose RRS score was 0-37.5% of those with highest risk scores (P =
      0.0002). We derived a simple formula for readmission risk as 8 and 4% more for
      each additional readmission risk factor. The positive predictive value for RRS >0
      was low, while the negative predictive value for this cutoff was 95%.
      CONCLUSIONS: An easily calculated 7-point score can be used to estimate
      readmission risk. This tool may be particularly useful for identifying lower risk
      patients who may not require intensive intervention, thus aiding in appropriate
      targeting of resources.

PMID- 24737835
TI  - Does regulating private long-term care facilities lead to better care? A study
      from Quebec, Canada.
AB  - OBJECTIVE: In the province of Quebec, Canada, long-term residential care is
      provided by two types of facilities: publicly funded accredited facilities and
      privately owned facilities in which care is privately financed and delivered.
      Following evidence that private facilities were delivering inadequate care, the
      provincial government decided to regulate this industry. We assessed the impact
      of regulation on care quality by comparing quality assessments made before and
      after regulation. In both periods, public facilities served as a comparison
      group. DESIGN: A cross-sectional study conducted in 2010-12 that incorporates
      data collected in 1995-2000. SETTINGS: Random samples of private and public
      facilities from two regions of Quebec. PARTICIPANTS: Random samples of disabled
      residents aged 65 years and over. In total, 451 residents from 145 care settings
      assessed in 1995-2000 were compared with 329 residents from 102 care settings
      assessed in 2010-12. INTERVENTION: Regulation introduced by the province in 2005,
      effective February 2007. MAIN OUTCOME MEASURE: Quality of care measured with the
      QUALCARE Scale. RESULTS: After regulation, fewer small-size facilities were in
      operation in the private market. Between the two study periods, the proportion of
      residents with severe disabilities decreased in private facilities whereas it
      remained >80% in their public counterparts. Meanwhile, quality of care improved
      significantly in private facilities, while worsening in their public
      counterparts, even after controlling for confounding. CONCLUSIONS: The private
      industry now provides better care to its residents. Improvement in care quality
      likely results in part from the closure of small homes and change in resident
      case-mix.

PMID- 24737836
TI  - Patient care transitions from the emergency department to the medicine ward:
      evaluation of a standardized electronic signout tool.
AB  - OBJECTIVE: To evaluate the impact of a new electronic handoff tool for emergency
      department to medicine ward patient transfers over a 1-year period. DESIGN:
      Prospective mixed-methods analysis of data submitted by medicine residents
      following admitting shifts before and after eSignout implementation. SETTING:
      University-based, tertiary-care hospital. PARTICIPANTS: Internal medicine
      resident physicians admitting patients from the emergency department.
      INTERVENTION: An electronic handoff tool (eSignout) utilizing automated paging
      communication and responsibility acceptance without mandatory verbal
      communication between emergency department and medicine ward providers. MAIN
      OUTCOME MEASURES: (i) Incidence of reported near misses/adverse events, (ii)
      communication of key clinical information and quality of verbal communication and
      (iii) characterization of near misses/adverse events. RESULTS: Seventy-eight of
      80 surveys (98%) and 1058 of 1388 surveys (76%) were completed before and after
      eSignout implementation. Compared with pre-intervention, residents in the post
      intervention period reported similar number of shifts with a near miss/adverse
      event (10.3 vs. 7.8%; P = 0.27), similar communication of key clinical
      information, and improved verbal signout quality, when it occurred. Compared with
      the former process requiring mandatory verbal communication, 93% believed the
      eSignout was more efficient and 61% preferred the eSignout. Patient safety issues
      related to perceived sufficiency/accuracy of diagnosis, treatment or disposition,
      and information quality. CONCLUSIONS: The eSignout was perceived as more
      efficient and preferred over the mandatory verbal signout process. Rates of
      reported adverse events were similar before and after the intervention. Our
      experience suggests electronic platforms with optional verbal communication can
      be used to standardize and improve the perceived efficiency of patient handoffs.

PMID- 24737837
TI  - Double meanings will not save the principle of double effect.
AB  - In an article somewhat ironically entitled "Disambiguating Clinical Intentions,"
      Lynn Jansen promotes an idea that should be bewildering to anyone familiar with
      the literature on the intention/foresight distinction. According to Jansen,
      "intention" has two commonsense meanings, one of which is equivalent to
      "foresight." Consequently, questions about intention are "infected" with
      ambiguity-people cannot tell what they mean and do not know how to answer them.
      This hypothesis is unsupported by evidence, but Jansen states it as if it were
      accepted fact. In this reply, we make explicit the multiple misrepresentations
      she has employed to make her hypothesis seem plausible. We also point out the
      ways in which it defies common sense. In particular, Jansen applies her thesis
      only to recent empirical research on the intentions of doctors, totally ignoring
      the widespread confusion that her assertion would imply in everyday life, in law,
      and indeed in religious and philosophical writings concerning the
      intention/foresight distinction and the Principle of Double Effect. 

PMID- 24737839
TI  - Not quite the full story on new antiplatelets.

PMID- 24737840
TI  - Not quite the full story on new antiplatelets.

PMID- 24737841
TI  - Canada ranks No. 14 in world for retirees.

PMID- 24737843
TI  - Making sense of an unexpected detrimental effect of sign language use in a visual
      task.
AB  - What supports deaf signers advantage over nonsigners on visuospatial short-term
      memory (STM) tasks is still a matter of debate. We compared the performance of 18
      deaf Italian Sign Language (LIS) users with that of a matched group of Italian
      hearing nonsigners in three different tasks: two versions of the Corsi Block
      test, namely span forward and span backward, and the Visual Pattern Test (VPT).
      Although the Corsi forward and backward are dynamic and mainly involve a spatial
      component, the VPT is static and taps primarily the visual component of STM.
      Signers significantly outperformed nonsigners on both versions of the Corsi Block
      test, whereas they performed significantly worse on the VPT. We suggest that the
      source of the different pattern lies in the static nature of the VPT versus the
      dynamic nature of the Corsi spans. 

PMID- 24737844
TI  - Relative contributions of cytochrome CYP3A4 versus CYP3A5 for CYP3A-cleared drugs
      assessed in vitro using a CYP3A4-selective inactivator (CYP3cide).
AB  - Metabolism by cytochrome P4503A (CYP3A) is the most prevalent clearance pathway
      for drugs. Designation of metabolism by CYP3A commonly refers to the potential
      contribution by one or both of two enzymes, CYP3A4 and CYP3A5. The metabolic
      turnover of 32 drugs known to be largely metabolized by CYP3A was examined in
      human liver microsomes (HLMs) from CYP3A5 expressers (*1/*1 genotype) and
      nonexpressers (*3/*3 genotype) in the presence and absence of ketoconazole and
      CYP3cide (a selective CYP3A4 inactivator) to calculate the contribution of CYP3A5
      to metabolism. Drugs with the highest contribution of CYP3A5 included atazanavir,
      vincristine, midazolam, vardenafil, otenabant, verapamil, and tacrolimus, whereas
      17 of the 32 tested showed negligible CYP3A5 contribution. For specific reactions
      in HLMs from *1/*1 donors, CYP3A5 contributes 55% and 44% to midazolam 1'- and 4
      hydroxylation, 16% to testosterone 6beta-hydroxylation, 56% and 19% to alprazolam
      1'- and 4-hydroxylation, 10% to tamoxifen N-demethylation, and 58% to atazanavir
      p-hydroxylation. Comparison of the in vitro observations to clinical
      pharmacokinetic data showed only a weak relationship between estimated
      contribution by CYP3A5 and impact of CYP3A5 genotype on oral clearance, in large
      part because of the scatter in clinical data and the low numbers of study
      subjects used in CYP3A5 pharmacogenetics studies. These data should be useful in
      guiding which drugs should be evaluated for differences in pharmacokinetics and
      metabolism between subjects expressing CYP3A5 and those who do not express this
      enzyme. 

PMID- 24737845
TI  - Analysis of patient satisfaction and donor-site morbidity after different types
      of breast reconstruction.
AB  - BACKGROUND AND AIMS: Breast reconstruction has been shown to improve quality of
      life. However, factors involved in long-term patient satisfaction are largely
      unknown. Our aim was to evaluate patient satisfaction and donor-site morbidity in
      five types of breast reconstruction. MATERIAL AND METHODS: A prospectively
      collected database of all breast surgery patients at Hospital Rudolfstiftung,
      Vienna, Austria, was searched for five types of breast reconstruction (2000
      2006): implant, latissimus dorsi-flap, latissimus dorsi-flap with implant, free
      transverse rectus abdominis musculocutaneous-flap, and deep inferior epigastric
      perforator-flap. Patients were sent a study-specific questionnaire to assess
      satisfaction. Short-form 36-item health survey was used to analyze (quality of
      life), and complication data were retrieved from the database and assessed during
      a follow-up visit. RESULTS: There were 257 patients identified, of whom, 126
      responded to the survey (17 implant, 5 latissimus dorsi + implant, 64 latissimus
      dorsi, 22 transverse rectus abdominis musculocutaneous, and 18 deep inferior
      epigastric perforator reconstructions). No statistical differences were found in
      complication or reoperation rates. Deep inferior epigastric perforator-flap
      patients were significantly more satisfied compared to patients from the implant
      group (p = 0.007). However, there was no significant difference regarding quality
      of life scores among the groups. After logistic regression analysis, only
      "impairment on daily life" showed to be independently correlated with patient
      satisfaction. This contrary to both operation type and complication rate which
      did not correlate with patient satisfaction. CONCLUSIONS: Our results indicate
      that operation type, complication rate, and revision rate did not independently
      correlate with patient satisfaction. Therefore, to further improve patient
      satisfaction, future research should be focused on other pro-operative factors,
      for example, patient education, expectations, and personality characteristics.

PMID- 24737846
TI  - Controversies in Initial Management of Open Fractures.
AB  - BACKGROUND: Treatment of open fractures continues to be a challenge for
      orthopedic and trauma surgeons, and early treatment recommendations, which
      persist in the literature for decades, often do not have supporting data.
      METHODS: This is a critical review of the literature surrounding controversies in
      the initial management of open fractures. It also focuses on the utility of
      negative pressure dressings in the care of associated complex wounds. Studies
      were selected based on their relevance to the treatment of open fractures.
      RESULTS: A total of 40 studies were included. The following topics were
      critically discussed: timing of initial debridement, antibiotic coverage, utility
      of obtaining cultures, and timing of wound closure. CONCLUSION: The majority of
      open fractures require urgent, not emergent, irrigation and debridement.
      Antibiotics are essential in preventing infection in open fractures. Timely wound
      closure after all necrotic tissue has been debrided decreases complications in
      open fractures. Finally, negative pressure wound therapy has dramatically changed
      the care of associated complex wounds.

PMID- 24737842
TI  - MYC and the art of microRNA maintenance.
AB  - MYC is a noncanonical transcription factor that binds to thousands of genomic
      loci and affects >15% of the human transcriptome, with surprisingly little
      overlap between MYC-bound and -regulated genes. This discordance raises the
      question whether MYC chooses its targets based on their individual biological
      effects ("a la carte") or by virtue of belonging to a certain group of genes (on
      a "prix fixe" basis). This review presents evidence for a prix fixe,
      posttranscriptional model whereby MYC initially deregulates a select number of
      microRNAs. These microRNAs then target a broad spectrum of genes based solely on
      the presence in their 3' UTRs (untranslated regions) of distinct "seed"
      sequences. Existing evidence suggests that there are significant microRNA
      components to all key MYC-driven phenotypes, including cell-cycle progression,
      apoptosis, metabolism, angiogenesis, metastasis, stemness, and hematopoiesis.
      Furthermore, each of these cell-intrinsic and -extrinsic phenotypes is likely
      attributable to deregulation of multiple microRNA targets acting in different,
      yet frequently overlapping, pathways. The habitual targeting of multiple genes
      within the same pathway might account for the robustness and persistence of MYC
      induced phenotypes. 

PMID- 24737847
TI  - The diagnostic value of a panel of serological markers in acute appendicitis.
AB  - BACKGROUND: Appendicitis is a frequent reason for hospital admissions. Elevated C
      reactive protein, white blood cell count, and serum bilirubin have been suggested
      as individual markers for appendicitis and appendiceal perforation. The aim of
      this study was to analyze if a combination of serologic markers could increase
      the prognostic accuracy of diagnosing non-perforated and perforated appendicitis.
      MATERIAL AND METHODS: Demographic data, histological findings, blood tests, and
      clinical symptoms were collected on all patients who underwent a diagnostic
      laparoscopy, a laparoscopic appendectomy, or conventional (open) appendectomy
      between May 2009 and May 2012 from a surgical department. The patients were
      grouped into those with either perforated appendicitis, non-perforated
      appendicitis, or differential diagnosis. Univariate and multivariate models were
      used to identify which markers were useful in predicting acute and perforated
      appendicitis, and receiving operating characteristics curves were used to find
      the specificity, sensitivity, and the negative and positive predictive values.
      RESULTS: A total of 1008 patients were operated under suspicion of appendicitis.
      From these, 700 patients had a pathologically verified inflamed appendix and 190
      had a perforated appendix. Patients with acute appendicitis had significantly
      higher blood levels of white blood cell, bilirubin, C-reactive protein, and
      alanine transaminase than patients without appendicitis. Patients with perforated
      appendicitis had significantly higher levels of white blood cell, bilirubin, and
      C-reactive protein than patients with non-perforated appendicitis. The highest
      positive predictive value to discriminate between acute appendicitis and non
      appendicitis was of a linear regression model combining white blood cell count,
      bilirubin, and alanine transaminase. C-reactive protein levels and a linear
      regression model, including white blood cell count, bilirubin, and C-reactive
      protein levels as variables, had the highest negative predictive values when
      discriminating between perforated and non-perforated appendicitis. CONCLUSION:
      Combining blood markers was useful in predicting appendicitis and perforated
      appendicitis. In addition to C-reactive protein and white cell count, blood
      levels of bilirubin, and alanine transaminase may be useful.

PMID- 24737848
TI  - Intraoperative motive for performing a laparoscopic appendectomy on a
      postoperative histological proven normal appendix.
AB  - BACKGROUND: Diagnostic laparoscopy is the ultimate tool to evaluate the appendix.
      However, the intraoperative evaluation of the appendix is difficult, as the
      negative appendectomy rate remains 12%-18%. The aim of this study is to analyze
      the intraoperative motive for performing a laparoscopic appendectomy of an
      appendix that was proven to be noninflamed after histological examination.
      METHODS: In 2008 and 2009, in five hospitals, operation reports of all negative
      laparoscopic appendectomies were retrospectively analyzed in order to assess the
      intraoperative motive for removing the appendix. RESULTS: A total of 1,465
      appendectomies were analyzed with an overall negative appendectomy rate of 9%
      (132/1,465). In 57% (841/1,465), a laparoscopic appendectomy was performed, with
      9% (n = 75) negative appendectomies. In 51% of the negative appendectomies, the
      visual assessment of the appendix was decisive in performing the appendectomy. In
      33%, the surgeon was in doubt whether the appendix was inflamed or normal. In 4%,
      the surgeon was aware he removed a healthy appendix, and in 9%, an appendectomy
      was performed for different reasons. CONCLUSION: In more than half of the
      microscopic healthy appendices, the surgeon was convinced of the diagnosis
      appendicitis during surgery. Intraoperative laparoscopic assessment of the
      appendix can be difficult.

PMID- 24737849
TI  - Pitfalls of femoral titanium elastic nailing.
AB  - BACKGROUND AND AIMS: Despite several potential complications of elastic
      intramedullary nailing, it is currently the treatment of choice for femoral
      diaphyseal fractures in school-aged children. This study aimed to critically
      evaluate the complications of titanium elastic nailing in pediatric femoral shaft
      fractures. MATERIAL AND METHODS: This study evaluated patients with a diaphyseal
      femoral fracture treated with titanium elastic nailing (TEN) in Tampere
      University Hospital in Finland. The study group included 32 children with a mean
      age of 9 years during a 5-year period, from 1 January 2003 to 31 December 2007.
      Data were collected from medical records and x-rays. Mean follow-up time was 42
      months. RESULTS: Of 32 patients, 9 (28%) reported a postoperative complication.
      Complications were associated with nail prominence in five (16%) patients and
      instability in four (12%) patients. In patients with nail prominence, the
      titanium elastic nailing-nail ends were unbent and 10-35 mm outside the cortex of
      the distal femur. The nail prominence caused pain and delayed knee mobilization
      until the nail was removed after a mean time of 4 months. In patients with
      fracture instability, the mean titanium elastic nailing-nail/medullary canal
      diameter ratio was 46% and periosteal callus formation was 5.4 mm at the first
      control. In those with stable fractures, the values were 66% and 9.2 mm,
      respectively. CONCLUSIONS: Based on this study, two types of pitfalls in a small
      volume center were found. Titanium elastic nail ends were left unbent and too
      long. We recommend palpating the nail ends to exclude nail prominence and to
      verify free movement of the knee after nail cutting and bending. Fracture
      instability was caused by inserting titanium elastic nailing-nails that were too
      narrow. To avoid this complication, careful preoperative planning to select the
      proper-size titanium elastic nailing-nails and intraoperative testing of fracture
      stability under continuous fluoroscopy after the operation is advised.

PMID- 24737850
TI  - A Decade of Advances in Military Trauma Care.
AB  - BACKGROUND: While combat casualty care shares many key concepts with civilian
      trauma systems, its unique features mandate certain practices that are distinct
      from the civilian ones. METHODS: This is a review of the most current literature
      on combat casualty care, based on computer database searches for studies on
      combat casualty care and military medicine. Studies were selected for inclusion
      in this review based on their relevance and contribution. RESULTS: Over the last
      decade, meticulous, international data collection and research efforts have led
      to significant improvements in military trauma care. Combat medicine has focused
      on the causes of preventable deaths and targeted on bleeding control and
      resuscitation strategies, as well as improved evacuation. En route care and
      forward surgical interventions have resulted in unprecedented low fatality rates
      and the saving of more lives. CONCLUSION: This overview of the developments in
      combat casualty care in recent years emphasizes medical practices that are
      characteristic of combat medicine, yet with the potential to save lives in other
      scenarios, as well.

PMID- 24737851
TI  - Resuscitative Thoracotomy: An Update.
AB  - BACKGROUND: Resuscitative thoracotomy is a heroic procedure that may offer the
      only survival hope for trauma patients in extremis. However, this operation has
      been the subject of much debate and its use, feasibility, outcomes, and cost are
      being continuously re-evaluated. METHODS: This is a review of the most current
      (after 2000) literature on resuscitative thoracotomy, based on computer database
      searches for studies on resuscitative thoracotomy, emergency department
      thoracotomy, and emergency thoracotomy. Studies were selected for inclusion in
      this review based on their relevance and contribution to our understanding of
      resuscitative thoracotomy. RESULTS: A total of 37 studies were included, and the
      following resuscitative thoracotomy-related topics were critically discussed:
      indications, biochemical profile, long-term outcome, organ donation, pre-hospital
      use, military use, international aspects, intra-aortic balloon occlusion,
      suspended animation, and cost and occupational exposure. CONCLUSIONS: This review
      demonstrates that the indications for resuscitative thoracotomy become clearer
      and that new information is available regarding its use in the pre-hospital urban
      environment and military settings. Furthermore, it points to new strategies to
      supplement resuscitative thoracotomy including intra-aortic balloon occlusion and
      suspended animation. Finally, it sheds light on the long-term outcomes, organ
      donation, and cost and occupational exposure following resuscitative thoracotomy.

PMID- 24737852
TI  - Completeness and correctness of cholecystectomy data in a national register-
      GallRiks.
AB  - BACKGROUND AND AIMS: To validate the Swedish Register for Gallstone Surgery and
      Endoscopic Retrograde Cholangiopancreatography (GallRiks) concerning completeness
      and correctness of entered data for cholecystectomies and evaluating the effect
      of repeated audits. It is crucial for any register to obtain a high accuracy in
      order to be a credible and reliable source for quality evaluation, research, and
      development. MATERIALS AND METHODS: Completeness was determined by cross-matching
      the register with the Swedish National Patient Register. Completeness and overall
      correctness were assessed by comparing registered data to medical records.
      Correctness for rare occasions, such as bile duct injuries, was evaluated by
      comparing with claims sent to the Swedish Patient Insurance. RESULTS: Of 64,538
      cholecystectomies, 82.9% of the operations were registered in GallRiks and the
      coverage increased over time. By random sample, 94,919 sets of data were
      available for comparison at the first and second audit and the entries were found
      to be correct in 97.2% and 98.2% cases, respectively. A 100% correctness for bile
      duct injuries (n = 40) was seen when the index-operation was registered in
      GallRiks. CONCLUSION: GallRiks demonstrates high completeness, high correctness
      of entered data, and no indications of failure to report serious adverse events.
      Repeated audits increased the quality of registered data. GallRiks may be used
      for clinical evaluation on local and national level and the database enables
      scientific studies to be performed.

PMID- 24737853
TI  - Post-endoscopic retrograde cholangiopancreaticography complications in liver
      transplanted patients, a single-center experience.
AB  - BACKGROUND: Complications in the biliary tract occur in 5%-30% after liver
      transplantation and the main part of the complications is successfully managed
      with endoscopic retrograde cholangiopancreaticography (ERCP). The incidence and
      risk factors for post-ERCP complications in liver transplantation patients are
      not well described. Our objective was to define the frequency of post-ERCP
      complications in liver transplantation patients at the Abdominal Center,
      Rigshospitalet, the only Liver Transplantation Center in Denmark. METHODS:
      Retrospective study of all ERCPs performed in liver transplantation patients
      during a 9-year period. RESULTS: A total of 292 ERCPs were included. Overall post
      ERCP complications occurred in 24 procedures (8.2%): pancreatitis in 8 (2.7%),
      bleeding in 5 (1.7%), and cholangitis in 13 (4.5%) procedures. Simultaneous
      pancreatitis and cholangitis, and simultaneous bleeding and cholangitis occurred
      after two procedures, respectively. Multivariate analysis concerning overall
      complications identified biliary sphincterotomy (p = 0.006) and time since liver
      transplantation within 90 days postoperatively (p = 0.044) as risk factors for
      post-ERCP complications. Specifically concerning post-ERCP pancreatitis (PEP), it
      was found that pre-ERCP cholangitis was another independent risk factor for PEP
      (p = 0.026). Stent in the biliary tract prior to ERCP seemed to be protective (p
      = 0.041). CONCLUSIONS: Complications were of surprisingly mild degree. The rates
      of post-ERCP complications in our study were in line with previous studies with
      liver transplantation patients. Cholangitis prior to ERCP may be another risk
      factor for post-ERCP pancreatitis.

PMID- 24737854
TI  - Management of Bleeding Pelvic Fractures.
AB  - INTRODUCTION: In patients with severe pelvic fractures, exsanguinating hemorrhage
      represents the major cause of death within the first 24 h. Despite advances in
      management, the mortality rate in these patients remains significantly high.
      Recently, multiple treatment algorithms have been proposed for patients with
      severe pelvic fractures; however, the optimal modalities in particular in the
      hemodynamically unstable patient are still a matter of lively debate.This review
      article focuses on the recent body of knowledge on the different treatment
      options in patients with severe pelvic fractures and proposes the possible role
      of each modality in the management of these patients. METHODS: The MEDLINE
      database was searched for medical literature addressing the management of severe
      pelvic fractures with specific attention given to recent, clinically relevant
      publications. RESULTS: Angiography and embolization have emerged as excellent
      methods for addressing arterial bleeding. Mechanical pelvic stabilization and
      surgical hemostasis by pelvic packing, on the other hand, may effectively control
      venous bleeding and bleeding from the fractured bony surface. However, since
      there is no precise way to determine the major source of bleeding that is
      responsible for the hemodynamic instability, controversy remains over the timing
      and optimal order of angiography, mechanical pelvic stabilization, and packing.
      CONCLUSIONS: The author's own approach to these patients includes angiographic
      embolization as a first-line treatment only in hemodynamically stable patients
      with an arterial blush seen in the computed tomography scan, indicating acute
      arterial bleeding. Hemodynamically unstable patients are immediately transferred
      to the operating room, where pelvic packing and mechanical stabilization of the
      pelvic ring are carried out. Optionally, a subsequent postoperative angio
      embolization is performed if signs of further bleeding remain present.

PMID- 24737855
TI  - Factors predicting the development of early osteoarthritis following lateral
      tibial plateau fractures: mid-term clinical and radiographic outcomes of 73
      operatively treated patients.
AB  - BACKGROUND AND AIMS: The indications for operative treatment of lateral tibial
      plateau fractures are still controversial. The objective of this study was to
      determine whether residual articular surface depression and valgus malalignment
      of plated lateral tibial plateau fractures at medium-term follow-up affect the
      clinical and radiographic outcomes. MATERIAL AND METHODS: A chart review of
      patients with operatively treated (AO type B3.1) tibial plateau fractures that
      were admitted to our level I trauma center between 2002 and 2008 was performed.
      Out of 123 patients, 73 were available to participate in a clinical and
      radiographic follow-up examination. The mean follow-up time was 54 months.
      Patients were clinically assessed and completed the Lysholm knee score and
      Western Ontario and McMaster Universities Osteoarthritis Index. Maximal articular
      surface depression, radiological mechanical axis, and degree of posttraumatic
      osteoarthritis were evaluated from standing radiographs. RESULTS: Patients with
      valgus malalignment of 5 degrees  or greater at follow-up developed more advanced
      osteoarthritis (Kellgren-Lawrence grade 3-4) than patients with a normal
      mechanical axis (p = 0.006). Similarly, patients with articular depression
      greater than 2 mm at follow-up also developed more advanced osteoarthritis
      compared to patients with a depression of 2 mm or less (p = 0.001). The degree of
      valgus malalignment or articular depression had no effect on the Western Ontario
      and McMaster Universities Osteoarthritis Index or Lysholm scores. CONCLUSIONS:
      The postoperative articular congruity and normal mechanical axis of the lower leg
      after plate fixation in lateral tibial plateau fractures seem to have a role in
      prevention of posttraumatic osteoarthritis but does not appear to predict
      clinical outcome at medium-term follow-up. The role of initial dislocation and
      associated cartilage damage in the development of osteoarthritis following these
      fractures is still unknown.

PMID- 24737856
TI  - Trauma-Related Critical Care.
AB  - BACKGROUND: Post-trauma resuscitation has evolved based on civilian and wartime
      experiences over the last decade. Similarly, data from large multicenter
      randomized trials have changed the management of critically ill trauma patients
      in the intensive care unit. METHODS: This is a review of the literature focusing
      on areas relevant to the management of trauma patients in the intensive care
      unit. RESULTS: The following topics are included: (1) ventilator management, (2)
      trauma sepsis, (3) use of vasopressors in hemorrhage, (4) glucose control, (5)
      nutrition, and (6) hemodynamic monitoring. CONCLUSION: This review demonstrated
      the most recent data of trauma-related critical care. Further studies will be
      needed to settle growing controversies in the management of critically injured
      patients.

PMID- 24737857
TI  - Surgical wound infections after peripheral vascular surgery.
AB  - Surgical wound infection is one of the most common complications after peripheral
      vascular surgery. It increases the affected patient's risk for major amputation
      as well as mortality. Furthermore, surgical wound infection is an additional
      cost. Wound infections after vascular surgery are of multifactorial nature and
      generally result from the interplay of patient- and procedure-related factors.
      The use of systemic antibiotic prophylaxis may be the most important method in
      preventing surgical wound infections. In this review article, we report the
      current literature of surgical wound infections after peripheral vascular
      surgery. 

PMID- 24737858
TI  - Through the 10-mm Looking Glass: Advances in Minimally Invasive Surgery in
      Trauma.
AB  - BACKGROUND: Minimally invasive surgery is increasingly being used in trauma
      surgery as both a diagnostic and a therapeutic tool. However, significant debate
      regarding the accuracy, safety, and indications for minimally invasive surgery in
      trauma continues to impede widespread acceptance of these techniques among trauma
      surgeons. METHOD: Herein, we report a contemporary review of the current role of
      both laparoscopy and thoracoscopy in modern trauma surgery. Literature search was
      performed using PubMed database and the following keywords: "Trauma," "Minimally
      Invasive Surgery," "Laparoscopy," and "Thoracoscopy." RESULTS: Current
      recommendations advocate for the use of laparoscopy as a diagnostic tool in
      penetrating trauma for the diagnosis of diaphragm injuries and peritoneal
      violation. A significant body of research demonstrates that laparoscopy in select
      hemodynamically normal patients can significantly decrease nontherapeutic
      laparotomy rates and hospital costs and is highly sensitive and specific with
      very low missed injury rates, including small bowel injuries. Laparoscopic
      repairs to a wide breadth of abdominal and thoracic injuries have been reported
      with impressive results. Adherence to a standardized laparoscopic examination
      system and routine use of laparoscopy in elective or acute care practice strongly
      influence positive results with minimally invasive surgery in trauma. Video
      assisted thoracoscopic surgery is most commonly used for evaluation of diaphragm,
      evacuation of retained hemothorax, and management of ongoing bleeding post
      trauma. CONCLUSION: Minimally invasive surgery does offer several advantages
      compared to traditional open surgery and should be considered as an additional
      tool in the trauma surgeon's armamentarium in the care of select injured
      patients.

PMID- 24737859
TI  - The influence of dynein processivity control, MAPs, and microtubule ends on
      directional movement of a localising mRNA.
AB  - Many cellular constituents travel along microtubules in association with multiple
      copies of motor proteins. How the activity of these motors is regulated during
      cargo sorting is poorly understood. In this study, we address this issue using a
      novel in vitro assay for the motility of localising Drosophila mRNAs bound to
      native dynein-dynactin complexes. High precision tracking reveals that individual
      RNPs within a population undergo either diffusive, or highly processive, minus
      end-directed movements along microtubules. RNA localisation signals stimulate the
      processive movements, with regulation of dynein-dynactin's activity rather than
      its total copy number per RNP, responsible for this effect. Our data support a
      novel mechanism for multi-motor translocation based on the regulation of dynein
      processivity by discrete cargo-associated features. Studying the in vitro
      responses of RNPs to microtubule-associated proteins (MAPs) and microtubule ends
      provides insights into how an RNA population could navigate the cytoskeletal
      network and become anchored at its destination in cells. DOI:
      http://dx.doi.org/10.7554/eLife.01596.001. 

PMID- 24737860
TI  - Nuclear receptor LRH-1/NR5A2 is required and targetable for liver endoplasmic
      reticulum stress resolution.
AB  - Chronic endoplasmic reticulum (ER) stress results in toxicity that contributes to
      multiple human disorders. We report a stress resolution pathway initiated by the
      nuclear receptor LRH-1 that is independent of known unfolded protein response
      (UPR) pathways. Like mice lacking primary UPR components, hepatic Lrh-1-null mice
      cannot resolve ER stress, despite a functional UPR. In response to ER stress, LRH
      1 induces expression of the kinase Plk3, which phosphorylates and activates the
      transcription factor ATF2. Plk3-null mice also cannot resolve ER stress, and
      restoring Plk3 expression in Lrh-1-null cells rescues ER stress resolution.
      Reduced or heightened ATF2 activity also sensitizes or desensitizes cells to ER
      stress, respectively. LRH-1 agonist treatment increases ER stress resistance and
      decreases cell death. We conclude that LRH-1 initiates a novel pathway of ER
      stress resolution that is independent of the UPR, yet equivalently required.
      Targeting LRH-1 may be beneficial in human disorders associated with chronic ER
      stress. DOI: http://dx.doi.org/10.7554/eLife.01694.001. 

PMID- 24737861
TI  - FRET-based reporters for the direct visualization of abscisic acid concentration
      changes and distribution in Arabidopsis.
AB  - Abscisic acid (ABA) is a plant hormone that regulates plant growth and
      development and mediates abiotic stress responses. Direct cellular monitoring of
      dynamic ABA concentration changes in response to environmental cues is essential
      for understanding ABA action. We have developed ABAleons: ABA-specific
      optogenetic reporters that instantaneously convert the phytohormone-triggered
      interaction of ABA receptors with PP2C-type phosphatases to send a fluorescence
      resonance energy transfer (FRET) signal in response to ABA. We report the design,
      engineering and use of ABAleons with ABA affinities in the range of 100-600 nM to
      map ABA concentration changes in plant tissues with spatial and temporal
      resolution. High ABAleon expression can partially repress Arabidopsis ABA
      responses. ABAleons report ABA concentration differences in distinct cell types,
      ABA concentration increases in response to low humidity and NaCl in guard cells
      and to NaCl and osmotic stress in roots and ABA transport from the hypocotyl to
      the shoot and root. DOI: http://dx.doi.org/10.7554/eLife.01739.001. 

PMID- 24737862
TI  - Abscisic acid dynamics in roots detected with genetically encoded FRET sensors.
AB  - Cytosolic hormone levels must be tightly controlled at the level of influx,
      efflux, synthesis, degradation and compartmentation. To determine ABA dynamics at
      the single cell level, FRET sensors (ABACUS) covering a range ~0.2-800 uM were
      engineered using structure-guided design and a high-throughput screening
      platform. When expressed in yeast, ABACUS1 detected concentrative ABA uptake
      mediated by the AIT1/NRT1.2 transporter. Arabidopsis roots expressing ABACUS1-2u
      (Kd~2 uM) and ABACUS1-80u (Kd~80 uM) respond to perfusion with ABA in a
      concentration-dependent manner. The properties of the observed ABA accumulation
      in roots appear incompatible with the activity of known ABA transporters (AIT1,
      ABCG40). ABACUS reveals effects of external ABA on homeostasis, that is, ABA
      triggered induction of ABA degradation, modification, or compartmentation. ABACUS
      can be used to study ABA responses in mutants and quantitatively monitor ABA
      translocation and regulation, and identify missing components. The sensor
      screening platform promises to enable rapid fine-tuning of the ABA sensors and
      engineering of plant and animal hormone sensors to advance our understanding of
      hormone signaling. DOI: http://dx.doi.org/10.7554/eLife.01741.001. 

PMID- 24737863
TI  - The budding yeast Centromere DNA Element II wraps a stable Cse4 hemisome in
      either orientation in vivo.
AB  - In budding yeast, a single cenH3 (Cse4) nucleosome occupies the ~120-bp
      functional centromere, however conflicting structural models for the particle
      have been proposed. To resolve this controversy, we have applied H4S47C-anchored
      cleavage mapping, which reveals the precise position of histone H4 in every
      nucleosome in the genome. We find that cleavage patterns at centromeres are
      unique within the genome and are incompatible with symmetrical structures,
      including octameric nucleosomes and (Cse4/H4)2 tetrasomes. Centromere cleavage
      patterns are compatible with a precisely positioned core structure, one in which
      each of the 16 yeast centromeres is occupied by oppositely oriented
      Cse4/H4/H2A/H2B hemisomes in two rotational phases within the population.
      Centromere-specific hemisomes are also inferred from distances observed between
      closely-spaced H4 cleavages, as predicted from structural modeling. Our results
      indicate that the orientation and rotational position of the stable hemisome at
      each yeast centromere is not specified by the functional centromere sequence.
      DOI: http://dx.doi.org/10.7554/eLife.01861.001. 

PMID- 24737864
TI  - The nucleosomal barrier to promoter escape by RNA polymerase II is overcome by
      the chromatin remodeler Chd1.
AB  - RNA polymerase II (PolII) transcribes RNA within a chromatin context, with
      nucleosomes acting as barriers to transcription. Despite these barriers,
      transcription through chromatin in vivo is highly efficient, suggesting the
      existence of factors that overcome this obstacle. To increase the resolution
      obtained by standard chromatin immunoprecipitation, we developed a novel strategy
      using micrococcal nuclease digestion of cross-linked chromatin. We find that the
      chromatin remodeler Chd1 is recruited to promoter proximal nucleosomes of genes
      undergoing active transcription, where Chd1 is responsible for the vast majority
      of PolII-directed nucleosome turnover. The expression of a dominant negative form
      of Chd1 results in increased stalling of PolII past the entry site of the
      promoter proximal nucleosomes. We find that Chd1 evicts nucleosomes downstream of
      the promoter in order to overcome the nucleosomal barrier and enable PolII
      promoter escape, thus providing mechanistic insight into the role of Chd1 in
      transcription and pluripotency. DOI: http://dx.doi.org/10.7554/eLife.02042.001. 

PMID- 24737866
TI  - Genes for regeneration.
AB  - FoxA, an evolutionarily conserved gene involved in the development of the
      digestive system in many animals, has an important role in regeneration in
      flatworms. 

PMID- 24737865
TI  - Selective amputation of the pharynx identifies a FoxA-dependent regeneration
      program in planaria.
AB  - Planarian flatworms regenerate every organ after amputation. Adult pluripotent
      stem cells drive this ability, but how injury activates and directs stem cells
      into the appropriate lineages is unclear. Here we describe a single-organ
      regeneration assay in which ejection of the planarian pharynx is selectively
      induced by brief exposure of animals to sodium azide. To identify genes required
      for pharynx regeneration, we performed an RNAi screen of 356 genes upregulated
      after amputation, using successful feeding as a proxy for regeneration. We found
      that knockdown of 20 genes caused a wide range of regeneration phenotypes and
      that RNAi of the forkhead transcription factor FoxA, which is expressed in a
      subpopulation of stem cells, specifically inhibited regrowth of the pharynx.
      Selective amputation of the pharynx therefore permits the identification of genes
      required for organ-specific regeneration and suggests an ancient function for
      FoxA-dependent transcriptional programs in driving regeneration. DOI:
      http://dx.doi.org/10.7554/eLife.02238.001. 

PMID- 24737867
TI  - Plant biologists FRET over stress.
AB  - Two independent research labs have developed fluorescent biosensors to report the
      levels of the stress hormone, abscisic acid, within cells in living plants in
      real-time. 

PMID- 24737868
TI  - Dendritic cell maturation: functional specialization through signaling
      specificity and transcriptional programming.
AB  - Dendritic cells (DC) are key regulators of both protective immune responses and
      tolerance to self-antigens. Soon after their discovery in lymphoid tissues by
      Steinman and Cohn, as cells with the unique ability to prime naive antigen
      specific T cells, it was realized that DC can exist in at least two distinctive
      states characterized by morphological, phenotypic and functional changes-this led
      to the description of DC maturation. It is now well appreciated that there are
      several subsets of DC in both lymphoid and non-lymphoid tissues of mammals, and
      these cells show remarkable functional specialization and specificity in their
      roles in tolerance and immunity. This review will focus on the specific
      characteristics of DC subsets and how their functional specialization may be
      regulated by distinctive gene expression programs and signaling responses in both
      steady-state and in the context of inflammation. In particular, we will highlight
      the common and distinctive genes and signaling pathways that are associated with
      the functional maturation of DC subsets.

PMID- 24737869
TI  - Maternally inherited genetic variants of CADPS2 are present in autism spectrum
      disorders and intellectual disability patients.
AB  - Intellectual disability (ID) and autism spectrum disorders (ASDs) are complex
      neuropsychiatric conditions, with overlapping clinical boundaries in many
      patients. We identified a novel intragenic deletion of maternal origin in two
      siblings with mild ID and epilepsy in the CADPS2 gene, encoding for a synaptic
      protein involved in neurotrophin release and interaction with dopamine receptor
      type 2 (D2DR). Mutation screening of 223 additional patients (187 with ASD and 36
      with ID) identified a missense change of maternal origin disrupting CADPS2/D2DR
      interaction. CADPS2 allelic expression was tested in blood and different adult
      human brain regions, revealing that the gene was monoallelically expressed in
      blood and amygdala, and the expressed allele was the one of maternal origin.
      Cadps2 gene expression performed in mice at different developmental stages was
      biallelic in the postnatal and adult stages; however, a monoallelic (maternal)
      expression was detected in the embryonal stage, suggesting that CADPS2 is
      subjected to tissue- and temporal-specific regulation in human and mice. We
      suggest that CADPS2 variants may contribute to ID/ASD development, possibly
      through a parent-of-origin effect.

PMID- 24737870
TI  - HES6 drives a critical AR transcriptional programme to induce castration
      resistant prostate cancer through activation of an E2F1-mediated cell cycle
      network.
AB  - Castrate-resistant prostate cancer (CRPC) is poorly characterized and
      heterogeneous and while the androgen receptor (AR) is of singular importance,
      other factors such as c-Myc and the E2F family also play a role in later stage
      disease. HES6 is a transcription co-factor associated with stem cell
      characteristics in neural tissue. Here we show that HES6 is up-regulated in
      aggressive human prostate cancer and drives castration-resistant tumour growth in
      the absence of ligand binding by enhancing the transcriptional activity of the
      AR, which is preferentially directed to a regulatory network enriched for
      transcription factors such as E2F1. In the clinical setting, we have uncovered a
      HES6-associated signature that predicts poor outcome in prostate cancer, which
      can be pharmacologically targeted by inhibition of PLK1 with restoration of
      sensitivity to castration. We have therefore shown for the first time the
      critical role of HES6 in the development of CRPC and identified its potential in
      patient-specific therapeutic strategies. 

PMID- 24737871
TI  - Monocyte-derived dendritic cells promote T follicular helper cell
      differentiation.
AB  - To be effective, protein priming must induce the development of a distinct
      lineage of CD4(+) T cells named T follicular helper (Tfh) cells, which regulate
      the differentiation of high-affinity memory B cells and long-lived plasma cells.
      In this context, we tested how adjuvantation with CpG, the Toll-like receptor 9
      agonist used in clinics, contributes to antigen-specific T-cell-dependent B-cell
      responses in vivo. We found that addition of CpG to other vaccine adjuvant
      increased the differentiation of antigen-specific Tfh cells without changing the
      overall magnitude of the T-cell response. This phenomenon correlated with an
      enhancement of the germinal centre reaction, antigen-specific plasma cells and
      circulating antibodies. We comprehensively demonstrated that, in addition to the
      classical Tfh-cell differentiation mediated by conventional DC, the promoting
      effect due to CpG was orchestrated in vivo by antigen presentation and IL-6
      secreted by monocyte-derived dendritic cells (DC) as shown in their absence.
      Thus, while conventional DC initiate T-cell responses, targeting monocyte-derived
      DC specifically enhances the Tfh programme needed to regulate high-affinity B
      cell protection in vivo. 

PMID- 24737873
TI  - Chromophore-assisted laser inactivation--towards a spatiotemporal-functional
      analysis of proteins, and the ablation of chromatin, organelle and cell function.
AB  - Chromophore-assisted laser or light inactivation (CALI) has been employed as a
      promising technique to achieve spatiotemporal knockdown or loss-of-function of
      target molecules in situ. CALI is performed using photosensitizers as generators
      of reactive oxygen species (ROS). There are two CALI approaches that use either
      transgenic tags with chemical photosensitizers, or genetically encoded
      fluorescent protein fusions. Using spatially restricted microscopy illumination,
      CALI can address questions regarding, for example, protein isoforms, subcellular
      localization or phase-specific analyses of multifunctional proteins that other
      knockdown approaches, such as RNA interference or treatment with chemicals,
      cannot. Furthermore, rescue experiments can clarify the phenotypic capabilities
      of CALI after the depletion of endogenous targets. CALI can also provide
      information about individual events that are involved in the function of a target
      protein and highlight them in multifactorial events. Beyond functional analysis
      of proteins, CALI of nuclear proteins can be performed to induce cell cycle
      arrest, chromatin- or locus-specific DNA damage. Even at organelle level - such
      as in mitochondria, the plasma membrane or lysosomes - CALI can trigger cell
      death. Moreover, CALI has emerged as an optogenetic tool to switch off signaling
      pathways, including the optical depletion of individual neurons. In this
      Commentary, we review recent applications of CALI and discuss the utility and
      effective use of CALI to address open questions in cell biology.

PMID- 24737874
TI  - Potential approaches to sustainable, long-lasting payment reform in oncology.
AB  - With unsustainable and rising health care costs reaching what are regularly
      termed crisis levels, the United States' current fragmented and inefficient
      health care system is in need of reforms that will allow oncology practices to
      adapt to changing delivery systems that put the patient at the center of care.
      Oncology accounts for roughly 10% of all health care costs and is a prime target
      for reform-minded stakeholders, particularly in the realm of reimbursement for
      care. ASCO believes that successful physician payment reform will be physician
      led and driven. This article was developed by the ASCO Clinical Practice
      Committee Payment Reform Workgroup and underwent subsequent review and approval
      by the full Clinical Practice Committee and the ASCO Board of Directors. The
      following represents an abridged version of the original document, edited for
      length. The entire document may be found at www.asco.org/paymentreform. It
      includes a critical survey of the current reimbursement landscape and lays out
      the foundation for a comprehensive, multifaceted solution that would replace the
      current fee for service structure. This foundation includes quality measurements
      and incentives, a replacement for the current "buy and bill" system for
      chemotherapy drugs, value-based pathways, episodic or bundled care payments, and
      care coordination to decrease use of expensive resources. ASCO intends to pursue
      further development, modeling, and testing of these concepts and invites others
      in the oncology community to prepare to lead efforts to a more rational and
      stable payment plan that will support high-quality care for our patients. 

PMID- 24737872
TI  - Nuclear receptors rock around the clock.
AB  - Circadian rhythms characterize almost every aspect of human physiology,
      endocrinology, xenobiotic detoxification, cell growth, and behavior. Modern
      lifestyles that disrupt our normal circadian rhythms are increasingly thought to
      contribute to various disease conditions ranging from depression and metabolic
      disorders to cancer. This self-sustained time-keeping system is generated and
      maintained by an endogenous molecular machine, the circadian clock, which is a
      transcriptional mechanism composed of the transcription factors CLOCK and BMAL
      and their co-repressors, PER and CRY. Nuclear receptors (NRs) represent a large
      family of hormone-sensitive transcriptional regulators involved in a myriad of
      biological processes such as development, energy metabolism, reproduction,
      inflammation, and tissue homeostasis. Recent studies point not only to NR
      regulation by the clock, but also to NR regulation of the clock itself. Here, we
      discuss recent studies that functionally and mechanistically implicate NRs as key
      components of both the universal and adaptive circadian clock mechanisms. As
      proven pharmacological targets, nuclear receptors are promising targets for
      therapeutic control of many pathological conditions associated with the
      disruption of circadian rhythm. 

PMID- 24737875
TI  - Erythropoiesis-stimulating agent use after changes in medicare reimbursement
      policies.
AB  - PURPOSE: Since 2004, concerns about the safety of erythropoiesis-stimulating
      agents (ESAs) have resulted in label changes and restrictions on their use. We
      examined changes in ESA use and blood transfusions over time. METHODS: The SEER
      Medicare database was used to identify patients age >= 65 years with breast,
      lung, prostate, ovary, or colon cancer, diagnosed between 2000 and 2007, who had
      a chemotherapy claim after their cancer diagnosis. We calculated the mean number
      of ESA claims per patient per year. Follow-up claims were available through 2008.
      We used multivariable logistic regression models to analyze the association of
      ESA use and extended ESA use with clinical and demographic variables. RESULTS:
      Among 121,169 patients identified, 46,063 (38%) received an ESA. ESA use
      increased from 12.4% to 16.2% by 2006 and then decreased to 7.9% by 2008.
      Similarly, the mean number of ESA claims per patient decreased steadily over the
      entire timeframe. The annual percentage of patients undergoing transfusion
      remained relatively constant (9% to 10%). In a Cox proportional hazards time
      dependent model, ESA use was positively associated with black race (odds ratio
      [OR], 1.11; 95% CI, 1.07 to 1.15), metropolitan location (OR, 1.17; 95% CI, 1.13
      to 1.21), metastatic disease (OR, 1.39; 95% CI, 1.35 to 1.41), female sex (OR,
      1.17; 95% CI, 1.14 to 1.20), > one comorbidity (OR, 1.29; 95% CI, 1.25 to 1.32),
      and tumor type. The number of denied claims increased over time. CONCLUSION: Our
      study demonstrated a rapid decline in the percentage of patients treated with
      ESAs after changes to reimbursement policy, but not after warnings about use.
      Reimbursement restrictions of other overused or off-label drugs may help reduce
      health care expenditures.

PMID- 24737876
TI  - Changes in the care of non-small-cell lung cancer after audit and feedback: the
      Florida initiative for quality cancer care.
AB  - PURPOSE: Audit and feedback have been widely used to enhance the performance of
      various medical practices. Non-small-cell lung cancer (NSCLC) is one of the most
      common diseases encountered in medical oncology practice. We investigated the use
      of audit and feedback to improve the care of NSCLC. METHODS: Medical records were
      reviewed for patients with NSCLC first seen by a medical oncologist in 2006 (n =
      518) and 2009 (n = 573) at 10 oncology practices participating in the Florida
      Initiative for Quality Cancer Care. In 2008, feedback from 2006 audit results was
      provided to practices, which then independently undertook steps to improve their
      performance. Sixteen quality-of-care indicators (QCIs) were evaluated on both
      time points and were examined for changes in adherence over time. RESULTS: A
      statistically significant increase in adherence was observed for five of 16 QCIs.
      Adherence to brain staging using magnetic resonance imaging or computed
      tomography scan for stage III NSCLC (57.8% in 2006 v 82.8% in 2009; P = .001),
      availability of chemotherapy flow sheet (89.2% v 97.0%; P < .001), documentation
      of performance status for stage III and IV disease (43.4% v 51.3%; P < .001),
      availability of pathology report for patients undergoing surgery (95.2% v 99.2%;
      P = .02), and availability of signed chemotherapy consent (69.5% v 76.3%; P =
      .04). There were no statistically significant decreases in adherence on any QCIs.
      CONCLUSION: Audit with feedback was associated with a modest but important
      improvement in the treatment of NSCLC. Whether these changes are durable will
      require long-term follow-up.

PMID- 24737877
TI  - Policy Statement on the 340B Drug Pricing Program by the American Society of
      Clinical Oncology.

PMID- 24737878
TI  - Supersized viruses.

PMID- 24737880
TI  - A case of severe thrombocytopaenia associated with acute HIV-1 infection.
AB  - A 23-year-old man was admitted to our hospital with severe thrombocytopaenia. He
      had unprotected sexual contact 6 weeks earlier. He was diagnosed with acute HIV
      infection by means of HIV RNA viral load testing and HIV-associated
      thrombocytopaenia. Although his thrombocytopaenia improved immediately with short
      term dexamethasone therapy, this effect was not sustained after cessation of
      therapy. Antiretroviral therapy including raltegravir was initiated, and the
      patient recovered from severe thrombocytopaenia within several days. The findings
      from this case suggest that acute HIV infection should be suspected with
      unexplained thrombocytopaenia, and that antiretroviral therapy is the treatment
      of choice for severe HIV-associated thrombocytopaenia, even when in the early
      period following acquisition of the virus. 

PMID- 24737881
TI  - Factors associated with HIV and syphilis co-infection among men who have sex with
      men in seven Chinese cities.
AB  - HIV-syphilis co-infection is often cited as a major reason behind recent
      resurgence in syphilis prevalence among men who have sex with men in China. Most
      published literatures explore factors associated with either HIV or syphilis, but
      not their co-infection. We analysed data from a cross-sectional survey on men who
      have sex with men in seven Chinese cities. Snowball sampling was used to recruit
      participants for the survey. Socio-demographic and behavioural predictors for HIV
      syphilis mono/co-infection were examined using ordinal logistic regression.
      Factor scores were used to summarise (1) HIV-related knowledge and (2) access to
      HIV preventive services. Prevalence of HIV, syphilis, and their co-infection,
      among 2936 self-identified men who have sex with men, were 7.7%, 14.3%, and 2.6%,
      respectively. In the adjusted analysis, the significant positive correlates of
      poorer diagnoses (co-infection vs mono- and no infection or co- and mono
      infection vs no infection) were: 30 to 39 years and >=40 years age, education up
      to senior high school, unprotected anal intercourse, recent sexually transmitted
      infection symptoms, incorrect knowledge about routes of transmission, and access
      to preventive or counselling/testing services for HIV. For effective control of
      this dual epidemic, integrated HIV and syphilis surveillance and targeted
      intervention strategies for Chinese men who have sex with men are needed
      urgently.

PMID- 24737882
TI  - Extreme elevation of ferritin and creatine kinase in primary infection with HIV
      1.
AB  - The diagnosis of primary HIV-1 infection can be challenging, especially in the
      absence of reported risks or when presenting features are unusual and uncommon.
      We report an atypical case of primary HIV-1 infection with HIV-1 subtype C in a
      61-year old Caucasian man who presented with extreme hyperferritinaemia without
      iron overload and marked elevation of serum creatine kinase without
      rhabdomyolysis. In view of his symptomatic seroconversion and low baseline CD4+ T
      lymphocyte count, the patient was treated promptly with combination
      antiretroviral therapy. Subsequently, he made good clinical improvement on
      treatment and no opportunistic infections were diagnosed at presentation or as
      part of a later immune reconstitution syndrome. This novel case highlights the
      importance of clinical suspicion of HIV and suggests that primary HIV-1 infection
      should be considered in patients presenting with severe hyperferritinaemia or
      markedly elevated creatine kinase levels. Further studies are required to explain
      the causative biological mechanisms underlying this rare presentation. 

PMID- 24737883
TI  - The urethral smear as a tool in diagnosing adenovirus-induced urethritis.
AB  - Adenovirus is a recognised cause of non-gonococcal urethritis, and is not
      uncommonly associated with extragenital signs and symptoms. This case report
      describes a patient with symptoms of conjunctivitis, meatitis and urethritis. The
      urethral smear revealed almost exclusively monocytes microscopically, raising the
      suspicion of a viral aetiology. Results confirmed the presence of adenovirus in
      both the eyes and urethra. Despite waning reliance on the urethral smear in
      sexual health clinics, it can still be an important diagnostic tool in assessing
      the aetiology of non-specific urethritis. Finding an obvious monocytic cell
      response in the urethral smear can indicate a viral cause and allow the clinician
      to optimise management, counsel appropriately, and potentially reduce unnecessary
      antibiotic use. 

PMID- 24737884
TI  - Racial/Ethnic Disparities in Health-Related Quality of Life among Participants
      with Self-Reported Diabetes from NHANES 2001-2010.
AB  - PURPOSE: The purpose of this study is to investigate the racial/ethnic
      disparities in health-related quality of life (HRQOL) among adults with self
      reported diabetes and identify the different risk factors related to HRQOL for
      specific racial/ethnic groups in the United States. METHODS: National Health and
      Nutrition Examination Survey (NHANES) 2001-2010 participants (ages 20 years and
      older) who were self-identified as non-Hispanic white, non-Hispanic black, or
      Hispanic and with self-reported diabetes were included in the analysis (n =
      2594). The Centers for Disease Control and Prevention's HRQOL-4 was used to
      assess factors associated with HRQOL through multivariate logistic regression
      models with survey weighting. Stepwise model selection was applied to select the
      most significant factors for HRQOL in each racial/ethnic group. RESULTS: Hispanic
      participants were less likely to report 14 or more mentally unhealthy days and
      activity-limited days compared to non-Hispanic white counterparts, adjusting for
      age, sex, education, marital status, family poverty-income ratio (PIR), body mass
      index, smoking status, insurance coverage, and diabetes duration. Current smoking
      status and obesity were significantly associated with worse HRQOL among whites
      and blacks. Marital status predicted better HRQOL only among Hispanics. Having
      insurance coverage predicted better HRQOL among both blacks and Hispanics.
      Increased family PIR had a favorable association with the 4 HRQOL domains
      consistently among all races/ethnicities. CONCLUSION: Minimal racial/ethnic
      disparities in HRQOL were observed among US adults with self-reported diabetes.
      Support is offered for more individualized health care and communication with
      patients to target care and interventions that improve health and quality-of-life
      indicators.

PMID- 24737885
TI  - Lessons Learned from 20 Years of Diabetes Self-Management Research With Mexican
      Americans in Starr County, Texas.
AB  - PURPOSE: The purpose is to provide an overview of a 20-year research program
      aimed at testing diabetes self-management education interventions culturally
      tailored for Mexican Americans residing in an impoverished rural community on the
      Texas-Mexico border. METHODS: The research program involved focus group
      interviews to obtain community input, pilot testing to refine instruments and
      interventions, and community-based randomized controlled trials to examine
      intervention effects. Here the authors summarize lessons learned related to the
      (1) overall effects of culturally tailored diabetes self-management education;
      (2) impact of culture on study design, intervention development, health outcomes,
      and community acceptance; (3) benefits of and findings from multiple focus groups
      held over time in the community; and (4) personal and cultural motivators for
      behavioral change that were evident among study participants. RESULTS:
      Postintervention reductions in A1C ranged from 1.4 to 1.7 percentage points.
      Individuals who attended >= 50% of intervention sessions achieved a 6-percentage
      point reduction in A1C. Intervention teams included bilingual Mexican American
      nurses, dietitians, and promotoras, all recruited from the local community. Focus
      group interviews indicated that a traditional promotora model was not acceptable
      to the participants who wanted knowledgeable health professionals, or perceived
      authority figures, to lead intervention sessions while promotoras provided
      logistical support. Free glucometers and strips, family participation, and
      interpersonal dynamics within intervention groups motivated individuals to make
      healthier lifestyle choices. CONCLUSIONS: Culturally tailored diabetes
      interventions are effective in improving the health of socially disadvantaged
      minorities who bear a disproportional burden of type 2 diabetes, and these
      interventions are cost-effective.

PMID- 24737886
TI  - A prospective study on distribution of eschar in patients suspected of scrub
      typhus.
AB  - Scrub typhus is an acute febrile illness caused by a tick bite infected with the
      bacteria Orientia tsutsugamushi The clinical diagnosis is difficult as the
      symptoms are similar to other febrile illnesses such as dengue, typhoid,
      leptospirosis and so on. An eschar, if present, will narrow down the provisional
      diagnosis towards scrub typhus. There are no data on the preferential sites of
      tick bites in an Indian population. We present here the preferential sites of
      tick bites in a South Indian population of 123 cases positive for eschar.
      Geographically, clothing styles vary leading to the differences in the areas of
      skin exposed to the bite and thus the formation of eschars. Scrub typhus, if not
      treated, may lead to fatal complications. As scrub typhus is one of the most
      under-reported illnesses in the world, clinicians should look for the presence of
      an eschar in the preferential sites at least to narrow down the diagnosis and
      treatment. 

PMID- 24737887
TI  - PI3K isoform dependence of PTEN-deficient tumors can be altered by the genetic
      context.
AB  - There has been increasing interest in the use of isoform-selective inhibitors of
      phosphatidylinositide-3-kinase (PI3K) in cancer therapy. Using conditional
      deletion of the p110 catalytic isoforms of PI3K to predict sensitivity of cancer
      types to such inhibitors, we and others have demonstrated that tumors deficient
      of the phosphatase and tensin homolog (PTEN) are often dependent on the p110beta
      isoform of PI3K. Because human cancers usually arise due to multiple genetic
      events, determining whether other genetic alterations might alter the p110
      isoform requirements of PTEN-null tumors becomes a critical question. To
      investigate further the roles of p110 isoforms in PTEN-deficient tumors, we used
      a mouse model of ovarian endometrioid adenocarcinoma driven by concomitant
      activation of the rat sarcoma protein Kras, which is known to activate p110alpha,
      and loss of PTEN. In this model, ablation of p110beta had no effect on tumor
      growth, whereas p110alpha ablation blocked tumor formation. Because ablation of
      PTEN alone is often p110beta dependent, we wondered if the same held true in the
      ovary. Because PTEN loss alone in the ovary did not result in tumor formation, we
      tested PI3K isoform dependence in ovarian surface epithelium (OSE) cells
      deficient in both PTEN and p53. These cells were indeed p110beta dependent,
      whereas OSEs expressing activated Kras with or without PTEN loss were p110alpha
      dependent. Furthermore, isoform-selective inhibitors showed a similar pattern of
      the isoform dependence in established Kras(G12D)/PTEN-deficient tumors. Taken
      together, our data suggest that, whereas in some tissues PTEN-null tumors appear
      to inherently depend on p110beta, the p110 isoform reliance of PTEN-deficient
      tumors may be altered by concurrent mutations that activate p110alpha. 

PMID- 24737888
TI  - Designed IgM from glycoengineering.

PMID- 24737889
TI  - Aversive behavior induced by optogenetic inactivation of ventral tegmental area
      dopamine neurons is mediated by dopamine D2 receptors in the nucleus accumbens.
AB  - Dopamine (DA) transmission from the ventral tegmental area (VTA) is critical for
      controlling both rewarding and aversive behaviors. The transient silencing of DA
      neurons is one of the responses to aversive stimuli, but its consequences and
      neural mechanisms regarding aversive responses and learning have largely remained
      elusive. Here, we report that optogenetic inactivation of VTA DA neurons promptly
      down-regulated DA levels and induced up-regulation of the neural activity in the
      nucleus accumbens (NAc) as evaluated by Fos expression. This optogenetic
      suppression of DA neuron firing immediately evoked aversive responses to the
      previously preferred dark room and led to aversive learning toward the
      optogenetically conditioned place. Importantly, this place aversion was abolished
      by knockdown of dopamine D2 receptors but not by that of D1 receptors in the NAc.
      Silencing of DA neurons in the VTA was thus indispensable for inducing aversive
      responses and learning through dopamine D2 receptors in the NAc. 

PMID- 24737890
TI  - Plant salt stress status is transmitted systemically via propagating calcium
      waves.

PMID- 24737891
TI  - Nature's toolkit for microbial rhodopsin ion pumps.

PMID- 24737892
TI  - Practical bound for dimensionality in high-dimensional entanglement.

PMID- 24737894
TI  - Antioxidants and exercise: a tale of the complexities of relating signalling
      processes to physiological function?

PMID- 24737893
TI  - LRP1 is a receptor for Clostridium perfringens TpeL toxin indicating a two
      receptor model of clostridial glycosylating toxins.
AB  - Large glycosylating toxins are major virulence factors of various species of
      pathogenic Clostridia. Prototypes are Clostridium difficile toxins A and B, which
      cause antibiotics-associated diarrhea and pseudomembranous colitis. The current
      model of the toxins' action suggests that receptor binding is mediated by a C
      terminal domain of combined repetitive oligopeptides (CROP). This model is
      challenged by the glycosylating Clostridium perfringens large cytotoxin (TpeL
      toxin) that is devoid of the CROP domain but still intoxicates cells. Using a
      haploid genetic screen, we identified LDL receptor-related protein 1 (LRP1) as a
      host cell receptor for the TpeL toxin. LRP1-deficient cells are not able to take
      up TpeL and are not intoxicated. Expression of cluster IV of LRP1 is sufficient
      to rescue toxin uptake in these cells. By plasmon resonance spectroscopy, a KD
      value of 23 nM was determined for binding of TpeL to LRP1 cluster IV. The C
      terminus of TpeL (residues 1335-1779) represents the receptor-binding domain
      (RBD) of the toxin. RBD-like regions are conserved in all other clostridial
      glycosylating toxins preceding their CROP domain. CROP-deficient C. difficile
      toxin B is toxic to cells, depending on the RBD-like region (residues 1349-1811)
      but does not interact with LRP1. Our data indicate the presence of a second, CROP
      independent receptor-binding domain in clostridial glycosylating toxins and
      suggest a two-receptor model for the cellular uptake of clostridial glycosylating
      toxins. 

PMID- 24737895
TI  - Impairment of exercise hyperaemia in familial hypercholesterolaemia: complex
      interplay of vasodilators vs. vasoconstrictors.

PMID- 24737896
TI  - Lamprey breathing when feeding sucks: the respiratory rhythm generator of a
      parasitic fish.

PMID- 24737897
TI  - Increasing venous return as a strategy to prevent or reverse cardiac dysfunction
      following spinal cord injury.

PMID- 24737898
TI  - Heterogeneity of blood flow: impact of age on muscle specific tissue perfusion
      during exercise.

PMID- 24737899
TI  - Treating chemoreflex in heart failure: modulation or demolition?

PMID- 24737900
TI  - Reply from Noah J. Marcus, Rodrigo Del Rio and Harold D. Schultz.

PMID- 24737901
TI  - The physician scientist revisited.

PMID- 24737902
TI  - Republished: Non-alcoholic fatty liver disease: non-invasive investigation and
      risk stratification.
AB  - Non-alcoholic fatty liver disease (NAFLD) encompasses a histological spectrum of
      liver disease, from simple steatosis through to cirrhosis. As the worldwide rates
      of obesity have increased, NAFLD has become the commonest cause of liver disease
      in many developed countries, affecting up to a third of the population. The
      majority of patients have simple steatosis that carries a relatively benign
      prognosis. However, a significant minority have non-alcoholic steatohepatitis,
      and have increased liver related and cardiovascular mortality. Identifying those
      at risk of progressive disease is crucial. Liver biopsy remains the gold standard
      investigation for assessing stage of disease but its invasive nature makes it
      impractical for widespread use as a prognostic tool. Non-invasive tools for
      diagnosis and disease staging are required, reserving liver biopsy for those
      patients where it offers clinically relevant additional information. This review
      discusses the non-invasive modalities available for assessing steatosis,
      steatohepatitis and fibrosis. We propose a pragmatic approach for the assessment
      of patients with NAFLD to identify those at high risk of progressive disease who
      require referral to specialist services. 

PMID- 24737903
TI  - Republished: Antineutrophil cytoplasmic antibody-associated vasculitides: is it
      time to split up the group?
AB  - Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides are a
      heterogeneous group of diseases corresponding to necrotising inflammation of
      small vessels with a wide range of clinical presentations. At least two of the
      diseases are believed to exhibit a common ground of pathophysiological
      mechanisms. These are granulomatosis with polyangiitis (GPA, formerly known as
      Wegener's granulomatosis) and microscopic polyangiitis (MPA). ANCA directed
      against proteinase 3 (PR3) are preferentially associated with GPA, and anti
      myeloperoxidase (MPO) ANCA are associated mainly with MPA and eosinophilic GPA
      (formerly known as Churg-Strauss syndrome). Anti-MPO and anti-PR3 antibodies can
      activate neutrophils in vitro. In vivo data are available for humans and mice on
      the pathogenicity of anti-MPO but it is more controversial for PR3-ANCA. A recent
      genome-wide association study of patients with ANCA-associated vasculitides
      confirmed the genetic contribution to the pathogenesis of these conditions, with
      significant association of PR3-ANCA and human leukocyte antigen-DP and the genes
      encoding alpha1-antitrypsin and PR3. MPO-ANCA were significantly associated with
      human leukocyte antigen-DQ. Thus, recent results from epidemiological studies,
      genome-wide association study and therapeutic trials have suggested that these
      entities are, in fact, distinct. We have summarised these results and discuss the
      idea that these two entities should be studied separately as the nature of the
      two auto-antigens suggests at a molecular level despite shared ANCA involvement. 

PMID- 24737904
TI  - Medicine as poetry.

PMID- 24737905
TI  - Just what is going on in his head: a patient's journey after a severe traumatic
      brain injury.

PMID- 24737906
TI  - Calcium-independent opening of lid1 of a family I.3 lipase by a single Asp to Arg
      mutation at the calcium-binding site.
AB  - A family I.3 lipase from Pseudomonas sp. MIS38 (PML) has two lids, lid1 and lid2,
      which are open when it exhibits activity. A single calcium ion is required to
      anchor lid1 in the open conformation by coordination with two acidic residues
      (Asp153 and Asp157) in lid1 and three other residues. Lid1 adopts a long alpha
      helix in the open conformation, whereas it is sharply bent within this helix,
      such that Asp153 and Asp157 are distantly located to each other, in the closed
      conformation. To examine whether the mutation of Asp153 or Asp157 to a positively
      charged residue allows two residues at Positions 153 and 157 to come close with
      each other and thereby stabilizes the open conformation of lid1 even in the
      absence of calcium ions, five single mutant proteins (D153K-, D153R-, D153A-,
      D157K- and D157R-PMLs) and two double mutant proteins (D153A/D157A- and
      D153R/D157N-PMLs) were constructed. Of these mutant proteins, only D153R-PML
      exhibited activity in the absence of calcium ions. Its lipase and esterase
      activities were 7-fold lower and 4-fold higher than those of PML, respectively.
      These activities were lost by the mutation of Asp157 to Asn. These results
      suggest that lid1 of D153R-PML opens even in the absence of calcium ions due to
      electrostatic attraction between Arg153 and Asp157. 

PMID- 24737907
TI  - Development of quality indicators for an integrated approach of knee
      osteoarthritis.
AB  - OBJECTIVE: Osteoarthritis (OA) is a common cause of disability worldwide. Knee OA
      care is often suboptimal. A first necessary step in quality improvement is to
      gain a clear insight into usual care. We developed a set of evidence-based
      quality indicators for multidisciplinary high-quality knee OA care. METHODS: A
      Rand-modified Delphi method was used to develop quality indicators for knee OA
      diagnosis, therapy, and followup. Recommendations were extracted from
      international guidelines as well as existing sets of quality indicators and
      scored by a multidisciplinary expert panel. Based on median score,
      prioritization, and agreement, recommendations were labeled as having a high,
      uncertain, or low potential to measure quality of care and were discussed in a
      consensus meeting for inclusion or exclusion. Two final validation rounds yielded
      a core set of recommendations, which were translated into quality indicators.
      RESULTS: From a total of 86 recommendations and existing indicators, a core set
      of 29 recommendations was derived that allowed us to define high-quality knee OA
      care. From this core set, 22 recommendations were considered to be measurable in
      clinical practice and were transformed into a final set of 21 quality indicators
      regarding diagnosis, lifestyle/education/devices, therapy, and followup.
      CONCLUSION: Our study provides a robust set of 21 quality indicators for high
      quality knee OA care, measurable in clinical practice. These process indicators
      may be used to measure usual care and evaluate quality improvement interventions
      across the entire spectrum of disciplines involved in knee OA care.

PMID- 24737908
TI  - Potential role of hyaluronic acid on bone in osteoarthritis: matrix
      metalloproteinases, aggrecanases, and RANKL expression are partially prevented by
      hyaluronic acid in interleukin 1-stimulated osteoblasts.
AB  - OBJECTIVE: To determine the effect of hyaluronic acid (HA) on proteolytic enzymes
      and bone remodeling mediators induced by interleukin 1beta (IL-1beta) and related
      to cartilage catabolism in murine osteoblasts. METHODS: Osteoblasts were obtained
      from Swiss mice and cultured for 3 weeks. HA-treated osteoblasts were incubated
      with 100 MUg/ml HA during the last week of culture, then stimulated with IL-1beta
      (10 ng/ml) for 24 h. The expression of matrix metalloproteinases 3 and 13 (MMP-3
      and MMP-13), ADAMTS-4 and ADAMTS-5, tissue inhibitor of metalloproteinases
      (TIMP), osteoprotegerin, and receptor activator of nuclear factor-kappaB ligand
      (RANKL) was determined by real-time polymerase chain reaction. MMP-3 and MMP-13
      release was assessed by Western blot analysis. RESULTS: IL-1beta increased the
      mRNA levels of MMP-3 and MMP-13 and ADAMTS-4 and ADAMTS-5 and release of MMP-3
      and MMP-13. Seven days of HA treatment significantly prevented the IL-1beta
      increased mRNA levels of MMP-3 (-61%, p < 0.01), MMP-13 (-56%, p < 0.01), ADAMTS
      4 (-58%, p < 0.05), ADAMTS-5 (-52%, p < 0.01), and RANKL (-49%, p < 0.05), but
      not TIMP. As well, IL-1beta-induced production of MMP-3 and MMP-13 was inhibited,
      by 27% (p < 0.01) and 40% (p < 0.01), respectively. CONCLUSION: In an
      inflammatory context in murine osteoblasts, HA can inhibit the expression of MMP
      and ADAMTS. Because HA can counteract the production of these mediators in
      chondrocytes, its beneficial effect in osteoarthritis may be due to its action on
      cartilage and subchondral bone.

PMID- 24737909
TI  - Bone marrow edema on magnetic resonance imaging (MRI) of the sacroiliac joints is
      associated with development of fatty lesions on MRI over a 1-year interval in
      patients with early inflammatory low back pain: a 2-year followup study.
AB  - OBJECTIVE: To assess whether bone marrow edema (BME) detected on magnetic
      resonance imaging (MRI) of the sacroiliac joints (MRI-SIJ) is associated with
      development of structural changes on both MRI and pelvic radiographs in patients
      with early inflammatory back pain (IBP). METHODS: Patients with IBP <= 2 years
      were followed for 2 years with annual MRI-SIJ. MRI were scored for BME and
      structural changes (erosions and fatty lesions). Pelvic radiographs were graded
      according to the modified New York (mNY) criteria. With generalized estimated
      equation analysis, a time trend in the structural change scores was investigated.
      RESULTS: Sixty-eight patients [38% male; mean (SD) age 34.9 (10.3) yrs] were
      included. During the 2-year followup, pelvic radiograph grading remained
      constant. On MRI, the number of erosions per patient increased significantly
      (mean score 2.5 at baseline and 3.5 at 2-yr followup; p = 0.05). A trend was
      found for an increase in the number of fatty lesions per patient (mean score 5.4
      at baseline and 8.5 at 2-yr followup; p = 0.06). Overall, BME was associated with
      the development of fatty lesions (right SIJ: OR 3.13, 95% CI 1.06-9.20; left SIJ:
      OR 22.13, 95% CI 1.27-384.50), preferentially in quadrants showing resolution of
      BME. In contrast, BME (or the resolution thereof) was not associated with the
      development of erosions. CONCLUSION: BME at baseline, especially when it
      disappears over time, results in the development of fatty lesions, but an
      association with erosions could not be demonstrated.

PMID- 24737910
TI  - Significance of small renal artery lesions in patients with antineutrophil
      cytoplasmic antibody-associated glomerulonephritis.
AB  - OBJECTIVE: Antineutrophil cytoplasmic antibody (ANCA)-associated
      glomerulonephritis is a vasculitis affecting the glomerular capillaries and small
      renal arteries. Although crescent formation has been reported to be
      characteristic of this condition, the significance of coexisting vasculitis
      affecting the small renal arteries has not been investigated. METHODS: Fifty
      patients with ANCA-positive rapidly progressive glomerulonephritis whose renal
      biopsy specimens contained arterioles and/or interlobular arteries were
      retrospectively evaluated. Cellular crescents and/or necrotizing
      glomerulonephritis were noted in all 50 patients. Ten patients had vasculitis of
      the small renal arteries (group A) and 40 patients were without such vasculitis
      (group B). The clinical features of these 2 groups were compared. RESULTS: Group
      A comprised 4 patients who had granulomatosis with polyangiitis (GPA) and 6 with
      microscopic polyangiitis (MPA), while group B included 1 patient with GPA and 39
      with MPA. No patient in either group had eosinophilic granulomatosis with
      polyangiitis. The C-reactive protein (CRP) level was significantly higher in
      group A compared with group B (11.58 +/- 6.19 vs 2.7 +/- 3.55 mg/dl, p < 0.05),
      and pulmonary involvement was more frequent in group A than group B (80% vs
      37.5%, p < 0.05). CONCLUSION: In patients with ANCA-positive glomerulonephritis,
      vasculitis of small renal arteries may be associated with systemic vasculitis
      (including pulmonary involvement) because of elevated CRP, a systemic
      inflammatory marker related to overproduction of interleukin 6.

PMID- 24737911
TI  - Early increase of abdominal adiposity in patients with spondyloarthritis
      receiving anti-tumor necrosis factor-alpha treatment.
AB  - OBJECTIVE: Patients with spondyloarthritis (SpA) receiving anti-TNF-alpha
      treatment have an increase in fat mass. This may be relevant to cardiovascular
      risk. The aim of this study was to estimate visceral adipose tissue (VAT) and
      subcutaneous adipose tissue (SAT) changes by dual-energy x-ray absorptiometry
      (DEXA) in patients with SpA under anti-TNF-alpha therapy. METHODS: We used an
      ancillary protocol to an open, prospective 2-year followup study of patients with
      SpA. Waist circumference (WC), body weight, body mass index, VAT, and SAT were
      measured at baseline, 6 months, and 1 and 2 years. Univariate and multivariate
      analyses were performed to assess variables associated with VAT and SAT changes.
      RESULTS: A total of 85 patients were analyzed. Patients were 39.3 +/- 11.4 years
      old and mean baseline Bath Ankylosing Spondylitis Disease Activity Index was 55.0
      +/- 20.2. Treatment was effective according to clinical and biological variables,
      and body weight increased by 0.9 +/- 1.7 kg over 2 years. There was a significant
      gain in VAT after 6 months (13.7 +/- 20.6 cm(2), p < 0.0001), 1 year (21.0 +/-
      26.6 cm(2), p < 0.0001), and after 2 years (29.1 +/- 33.4 cm(2), p < 0.0001); and
      in SAT after 6 months (12.5 +/- 27.4 cm(2), p < 0.0001), 1 year (27.1 +/- 38.2
      cm(2), p < 0.0001), and after 2 years (31.9 +/- 53.2 cm(2), p < 0.0001). We could
      not find any determinant of these changes by multivariate analysis. CONCLUSION:
      In patients with SpA receiving anti-TNF-alpha therapy, there is an early
      significant increase in abdominal obesity with significant increase in both VAT
      and SAT after 1 and 2 years of treatment. Prospective studies are required to
      investigate the relationship between these changes and cardiovascular risk.

PMID- 24737912
TI  - The effect of golimumab therapy on disease activity and health-related quality of
      life in patients with ankylosing spondylitis: 2-year results of the GO-RAISE
      trial.
AB  - OBJECTIVE: To evaluate the effects of golimumab therapy on achieving inactive
      disease or major improvement, as assessed by the Ankylosing Spondylitis Disease
      Activity Score (ASDAS), and improvements in health-related quality of life
      (HRQOL) and productivity through 2 years in patients with AS. METHODS: In the
      phase III GO-RAISE trial, 356 patients were randomized to placebo with crossover
      to golimumab 50 mg at Week 24 (n = 78), golimumab 50 mg (n = 138), or golimumab
      100 mg (n = 140) at baseline and every 4 weeks. The proportions of patients with
      ASDAS major improvement (improvement >= 2.0) or inactive disease (score < 1.3)
      were determined. HRQOL was assessed using the 36-item Medical Outcomes Study
      Short Form-36 physical/mental component summary (SF-36 PCS/MCS) scores (normal
      score >= 50). The effect of disease on productivity was assessed by visual analog
      scale (0-10). Regression analyses on the association of disease activity and
      HRQOL were performed. The final assessment was at Week 104. RESULTS:
      Significantly greater proportions of golimumab-treated patients achieved ASDAS
      major improvement or inactive disease at weeks 14 and 24 versus placebo. Through
      Week 104, patients who achieved ASDAS inactive disease or major improvement had
      significantly greater improvements in SF-36 PCS and MCS scores and productivity
      than did patients not meeting these targets. Among all patients, achieving ASDAS
      inactive disease at weeks 52 and 104 was associated with normalized SF-36 PCS/MCS
      scores and significant improvements in work productivity. CONCLUSION: Greater
      proportions of golimumab-treated patients achieved ASDAS major improvement or
      inactive disease and improved HRQOL versus placebo. Achieving an inactive disease
      state by ASDAS criteria (< 1.3) was associated with normalized HRQOL through 2
      years.

PMID- 24737913
TI  - Folic acid and folinic acid for reducing side effects in patients receiving
      methotrexate for rheumatoid arthritis.
AB  - OBJECTIVE: To perform a systematic review of the benefits and harms of folic acid
      and folinic acid in reducing the mucosal, gastrointestinal, hepatic, and
      hematologic side effects of methotrexate (MTX); and to assess whether folic or
      folinic acid supplementation has any effect on MTX benefit. METHODS: We searched
      the Cochrane Library, MEDLINE, EMBASE, and US National Institutes of Health
      clinical trials registry from inception to March 2012. We selected all double
      blind, randomized, placebo-controlled clinical trials in which adult patients
      with rheumatoid arthritis (RA) were treated with MTX (dose <= 25 mg/week)
      concurrently with folate supplementation. We included only trials using low-dose
      folic or folinic acid (a starting dose of <= 7 mg weekly) because the high dose
      is no longer recommended or used. Data were extracted from the trials, and the
      trials were independently assessed for risk of bias using a predetermined set of
      criteria. RESULTS: Six trials with 624 patients were eligible for inclusion. Most
      studies had low or unclear risk of bias for key domains. The quality of the
      evidence was rated as "moderate" for each outcome as assessed by the Grading of
      Recommendations Assessment, Development, and Evaluation (GRADE) working group,
      with the exception of hematologic side effects, which were rated as "low." There
      was no significant heterogeneity between trials, including where folic acid and
      folinic acid studies were pooled. For patients supplemented with any form of
      exogenous folate (either folic or folinic acid) while receiving MTX therapy for
      RA, a 26% relative (9% absolute) risk reduction was seen for the incidence of
      gastrointestinal side effects such as nausea, vomiting, or abdominal pain (RR
      0.74, 95% CI 0.59 to 0.92; p = 0.008). Folic and folinic acid also appear to be
      protective against abnormal serum transaminase elevation caused by MTX, with a
      76.9% relative (16% absolute) risk reduction (RR 0.23, 95% CI 0.15 to 0.34; p <
      0.00001), as well as reducing patient withdrawal from MTX for any reason [60.8%
      relative (15.2% absolute) risk reduction, RR 0.39, 95% CI 0.28 to 0.53; p <
      0.00001]. CONCLUSION: The results support a protective effect of supplementation
      with either folic or folinic acid for patients with RA during treatment with MTX.
      There was a clinically important significant reduction shown in the incidence of
      GI side effects and hepatic dysfunction (as measured by elevated serum
      transaminase levels), as well as a clinically important significant reduction in
      discontinuation of MTX treatment for any reason.

PMID- 24737914
TI  - Prevalence of antinuclear antibodies in schoolchildren during puberty and
      possible relationship with musculoskeletal pain: a longitudinal study.
AB  - OBJECTIVE: The role of antinuclear antibodies (ANA) in children has still to be
      elucidated. The aim of our study was to evaluate the prevalence and persistence
      of ANA in schoolchildren during the puberty switch, and the possible relationship
      with chronic noninflammatory musculoskeletal pain (MSP). METHODS: Children aged 8
      13 years and attending 4 public schools underwent a clinical examination,
      focusing on pubertal stage and presence of chronic noninflammatory MSP.
      Laboratory tests to determine the autoantibody-profile were also performed.
      Subjects with ANA positivity (titer >= 1:80) and/or chronic noninflammatory MSP
      were re-evaluated 3 years later. RESULTS: Two hundred sixty-one subjects enrolled
      in the study and 12.3% were ANA-positive, equally distributed in terms of sex and
      pubertal status. Three years later, in the group of patients studied for chronic
      noninflammatory MSP (n = 67), ANA positivity significantly increased from 13.4%
      to 44.8%. In the ANA-positive cohort at baseline (n = 28), 92.9% of subjects were
      confirmed as being ANA-positive with a significantly increased titer. No
      association between ANA positivity and chronic noninflammatory MSP was found.
      CONCLUSION: ANA prevalence and titers increase during puberty, especially in
      females, but have no relationship with chronic noninflammatory MSP. This finding
      may be related to the complex hormonal changes during the puberty switch period
      and opens new insights into autoimmunity.

PMID- 24737915
TI  - Osteoarthritis incidence and trends in administrative health records from British
      Columbia, Canada.
AB  - OBJECTIVE: To calculate the incidence rates of osteoarthritis (OA) and to
      describe the changes in incidence using 18 years of administrative health
      records. METHODS: We analyzed visits to health professionals and hospital
      admission records in a random sample (n = 640,000) from British Columbia, Canada,
      from 1991/1992 through 2008/2009. OA was defined in 2 ways: (1) at least 1
      physician diagnosis or 1 hospital admission; and (2) at least 2 physician
      diagnoses in 2 years or 1 hospital admission. Crude and age-standardized rates
      were calculated, and the annual relative changes were estimated from the Poisson
      regression models. RESULTS: In 2008/2009, the overall crude incidence rate (95%
      CI) of OA using definition 1 was 14.6 (14.0-14.8); [12.5 (12.0-13.0) among men
      and 16.3 (15.8-16.8) among women] per 1000 person-years. The rates were lower by
      about 44% under definition 2. For the period 2000/2001-2008/2009, crude incidence
      rates based on definition 1 varied from 11.8 to 14.2 per 1000 person-years for
      men, and from 15.7 to 18.5 for women. Annually, on average, crude rates rose by
      about 2.5-3.3% for both men and women. The age-adjusted rates increased by 0.6
      0.8% among men and showed no trend among women. CONCLUSION: Our study generated
      updated incidence rates of administrative OA for the Province of British
      Columbia. Physician-diagnosed overall incidence rates of OA varied with the case
      definitions used; however, trends were similar in both case definitions. Age
      adjusted rates among men increased slightly during the period 2000/2001
      2008/2009. These findings have implications for projecting future prevalence and
      costs of OA.

PMID- 24737917
TI  - Acquisition of conditioned responding in a multiple schedule depends on the
      reinforcement's temporal contingency with each stimulus.
AB  - Forty mice acquired conditioned responses to stimuli presented in a multiple
      schedule with variable inter-trial intervals (ITIs). In some trials,
      reinforcement was preceded by a variable conditioned stimulus (CS), while other
      trials were reinforced following distinctive fixed-duration CS. A third stimulus
      was presented but never paired with reinforcement. Subjects in five groups
      experienced ITIs of different durations. Acquisition of responding to each
      stimulus depended only on the cycle-to-trial ratio (C/T), and thus on the
      temporal contingency of each stimulus. Acquisition was unaffected by whether CSs
      were of fixed or variable duration. 

PMID- 24737916
TI  - Early-life cocaine interferes with BDNF-mediated behavioral plasticity.
AB  - An important aspect of goal-directed action selection is differentiating between
      actions that are more or less likely to be reinforced. With repeated performance
      or psychostimulant exposure, however, actions can assume stimulus-elicited-or
      "habitual"-qualities that are resistant to change. We show that selective
      knockdown of prelimbic prefrontal cortical Brain-derived neurotrophic factor
      (Bdnf) increases sensitivity to response-outcome associations, blocking habit
      like behavioral inflexibility. A history of adolescent cocaine exposure, however,
      occludes the "beneficial" effects of Bdnf knockdown. This finding highlights a
      challenge in treating addiction-that drugs of abuse may bias decision-making
      toward habit systems even in individuals with putative neurobiological
      resiliencies. 

PMID- 24737918
TI  - Regulation of persistent activity in hippocampal mossy cells by inhibitory
      synaptic potentials.
AB  - The hippocampal formation receives strong cholinergic input from the
      septal/diagonal band complex. Although the functional effects of cholinergic
      activation have been extensively studied in pyramidal neurons within the
      hippocampus and entorhinal cortex, less is known about the role of cholinergic
      receptors on dentate gyrus neurons. Using intracellular recordings from rat
      dentate hilar neurons, we find that activation of m1-type muscarinic receptors
      selectively increases the excitability of glutamatergic mossy cells but not of
      hilar interneurons. Following brief stimuli, cholinergic modulation reveals a
      latent afterdepolarization response in mossy cells that can extend the duration
      of stimulus-evoked depolarization by >100 msec. Depolarizing stimuli also could
      trigger persistent firing in mossy cells exposed to carbachol or an m1 receptor
      agonist. Evoked IPSPs attenuated the ADP response in mossy cells. The functional
      effect of IPSPs was amplified during ADP responses triggered in the presence of
      cholinergic receptor agonists but not during slowly decaying simulated ADPs,
      suggesting that modulation of ADP responses by IPSPs arises from destabilization
      of the intrinsic currents underlying the ADP. Evoked IPSPs also could halt
      persistent firing triggered by depolarizing stimuli. These results show that
      through intrinsic properties modulated by muscarinic receptors, mossy cells can
      prolong depolarizing responses to excitatory input and extend the time window
      where multiple synaptic inputs can summate. By actively regulating the intrinsic
      response to synaptic input, inhibitory synaptic input can dynamically control the
      integration window that enables detection of coincident inputs and shape the
      spatial pattern of hilar cell activity. 

PMID- 24737919
TI  - Three-dimensional flow contrast imaging of deep tissue using noncontact diffuse
      correlation tomography.
AB  - This study extended our recently developed noncontact diffuse correlation
      spectroscopy flowmetry system into noncontact diffuse correlation tomography
      (ncDCT) for three-dimensional (3-D) flow imaging of deep tissue. A linear array
      of 15 photodetectors and two laser sources connected to a mobile lens-focusing
      system enabled automatic and noncontact scanning of flow in a region of interest.
      These boundary measurements were combined with a finite element framework for DCT
      image reconstruction implemented into an existing software package. This
      technique was tested in computer simulations and using a tissue-like phantom with
      anomaly flow contrast design. The cylindrical tube-shaped anomaly was clearly
      reconstructed in both simulation and phantom. Recovered and assigned flow
      contrast changes in anomaly were found to be highly correlated: regression slope
      = 1.00, R2 = 1.00, and p < 10-5 in simulation and regression slope >= 0.97, R2 >=
      0.96, and p < 10-3 in phantom. These results exhibit promise of our ncDCT
      technique for 3-D imaging of deep tissue blood flow heterogeneities.

PMID- 24737920
TI  - Confocal acoustic radiation force optical coherence elastography using a ring
      ultrasonic transducer.
AB  - We designed and developed a confocal acoustic radiation force optical coherence
      elastography system. A ring ultrasound transducer was used to achieve reflection
      mode excitation and generate an oscillating acoustic radiation force in order to
      generate displacements within the tissue, which were detected using the phase
      resolved optical coherence elastography method. Both phantom and human tissue
      tests indicate that this system is able to sense the stiffness difference of
      samples and quantitatively map the elastic property of materials. Our confocal
      setup promises a great potential for point by point elastic imaging in vivo and
      differentiation of diseased tissues from normal tissue.

PMID- 24737921
TI  - A new fiber-optic non-contact compact laser-ultrasound scanner for fast non
      destructive testing and evaluation of aircraft composites.
AB  - Laser ultrasonic (LU) inspection represents an attractive, non-contact method to
      evaluate composite materials. Current non-contact systems, however, have
      relatively low sensitivity compared to contact piezoelectric detection. They are
      also difficult to adjust, very expensive, and strongly influenced by
      environmental noise. Here, we demonstrate that most of these drawbacks can be
      eliminated by combining a new generation of compact, inexpensive fiber lasers
      with new developments in fiber telecommunication optics and an optimally designed
      balanced probe scheme. In particular, a new type of a balanced fiber-optic Sagnac
      interferometer is presented as part of an all-optical LU pump-probe system for
      non-destructive testing and evaluation of aircraft composites. The performance of
      the LU system is demonstrated on a composite sample with known defects. Wide-band
      ultrasound probe signals are generated directly at the sample surface with a
      pulsed fiber laser delivering nanosecond laser pulses at a repetition rate up to
      76 kHz rate with a pulse energy of 0.6 mJ. A balanced fiber-optic Sagnac
      interferometer is employed to detect pressure signals at the same point on the
      composite surface. A- and B-scans obtained with the Sagnac interferometer are
      compared to those made with a contact wide-band polyvinylidene fluoride
      transducer.

PMID- 24737923
TI  - Evaluation of usefulness of hs-CRP and ferritin assays in patients with nasal
      polyps.
AB  - BACKGROUND: Chronic nature of the nasal polyps, tendency to recurrence, and lack
      of satisfying treatment need the diagnostic's parameters which show early
      inflammatory state as ferritin and hs-CRP. The Aim of Study. Assessment of hs-CRP
      and ferritin blood levels in nasal polyps patients in evaluation of treatment
      efficacy. METHODS: All 38 patients were divided into 2 groups. Group I included
      19 patients with anti-inflammatory therapy 2 weeks after surgery. Group II
      included 19 patients without anti-inflammatory therapy 2 weeks after surgery. The
      levels of hs-CRP and ferritin have been assessed before and 2 and 6 weeks after
      surgical treatment. RESULTS: Research showed statistically significant difference
      of ferritin's concentration between examined groups 6 weeks after surgery (P <
      0.05) and statistically significant difference of hs-CRP concentration 2 and 6
      weeks after surgery (P < 0.05). CONCLUSION: (1) The analysis of serum ferritin
      and hs-CRP concentrations can be useful in early postoperative detection of
      inflammatory state in patients with nasal polyps and for the effectiveness of
      therapy. (2) Lack of correlation between mean ferritin and hs-CRP serum levels,
      at each diagnostic and monitoring stage, shows that they are independent and
      cannot be determined interchangeably.

PMID- 24737922
TI  - A Longitudinal Perspective on the Association between Cognition and Temperamental
      Shyness.
AB  - Moderate, yet relatively consistent, associations between cognitive performance
      and shyness have been reported throughout the child and adult literatures. The
      current study assessed longitudinal associations between cognition (i.e.,
      executive functioning) and parent-report temperamental shyness from infancy to
      early childhood and used temporal order to explore directionality of the
      relations. Two hundred eleven children contributed data at multiple ages (5
      months, 10-months, 2-years, 3-years, and 4-years). The results indicated a
      complex pattern of association between cognition and shyness in early development
      and provided tentative support for both cognitive ability and temperament as
      causal agents at different developmental time points.

PMID- 24737924
TI  - Built environment and Property Crime in Seattle, 1998-2000: A Bayesian Analysis.
AB  - The past decade has seen a rapid growth in the use of a spatial perspective in
      studies of crime. In part this growth has been driven by the availability of
      georeferenced data, and the tools to analyze and visualize them: geographic
      information systems (GIS), spatial analysis, and spatial statistics. In this
      paper we use exploratory spatial data analysis (ESDA) tools and Bayesian models
      to help better understand the spatial patterning and predictors of property crime
      in Seattle, Washington for 1998-2000, including a focus on built environment
      variables. We present results for aggregate property crime data as well as models
      for specific property crime types: residential burglary, nonresidential burglary,
      theft, auto theft, and arson. ESDA confirms the presence of spatial clustering of
      property crime and we seek to explain these patterns using spatial Poisson models
      implemented in WinBUGS. Our results indicate that built environment variables
      were significant predictors of property crime, especially the presence of a
      highway on auto theft and burglary.

PMID- 24737925
TI  - The time profile of Pentraxin 3 in patients with acute ST-elevation myocardial
      infarction and stable angina pectoris undergoing percutaneous coronary
      intervention.
AB  - BACKGROUND: High levels of Pentraxin 3 (PTX3) are reported in acute myocardial
      infarction (AMI). AIM: To investigate circulating levels and gene expression of
      PTX3 in patients with AMI and stable angina pectoris (AP) undergoing PCI.
      METHODS: Ten patients with AP and 20 patients with AMI were included. Blood
      samples were drawn before PCI in the AP group and after 3 and 12 hours and days
      1, 3, 5, 7, and 14 in both groups. RESULTS: Circulating PTX3 levels were higher
      in AMI compared to AP at 3 and 12 hours (P < 0.001 and P = 0.003). Within the AMI
      group, reduction from 3 hours to all later time points was observed (all P <=
      0.001). Within the AP group, increase from baseline to 3 hours (P = 0.022),
      followed by reductions thereafter (all P < 0.05), was observed. PTX3 mRNA
      increased in the AMI group from 3 hours to days 7 and 14 in a relative manner of
      62% and 73%, while a relative reduction from baseline to 3 and 12 hours of 29%
      and 37% was seen in the AP group. CONCLUSION: High circulating PTX3 levels
      shortly after PCI in AMI indicate that AMI itself influences PTX3 levels. PTX3
      mRNA might be in response to fluctuations in circulating levels.

PMID- 24737926
TI  - Bisphenol A alters beta-hCG and MIF release by human placenta: an in vitro study
      to understand the role of endometrial cells.
AB  - A proper fetomaternal immune-endocrine cross-talk in pregnancy is fundamental for
      reproductive success. This might be unbalanced by exposure to environmental
      chemicals, such as bisphenol A (BPA). As fetoplacental contamination with BPA
      originates from the maternal compartment, this study investigated the role of the
      endometrium in BPA effects on the placenta. To this end, in vitro decidualized
      stromal cells were exposed to BPA 1 nM, and their conditioned medium (diluted 1 :
      2) was used on chorionic villous explants from human placenta. Parallel cultures
      of placental explants were directly exposed to 0.5 nM BPA while, control cultures
      were exposed to the vehicle (EtOH 0.1%). After 24-48 h, culture medium from BPA
      treated and control cultures was assayed for concentration of hormone human
      Chorionic Gonadotropin ( beta -hCG) and cytokine Macrophage Migration Inhibitory
      Factor (MIF). The results showed that direct exposure to BPA stimulated the
      release of both MIF and beta -hCG. These effects were abolished/diminished in
      placental cultures exposed to endometrial cell-conditioned medium. GM-MS analysis
      revealed that endometrial cells retain BPA, thus reducing the availability of
      this chemical for the placenta. The data obtained highlight the importance of in
      vitro models including the maternal component in reproducing the effects of
      environmental chemicals on human fetus/placenta.

PMID- 24737927
TI  - Plasma Anti-Glycan Antibody Profiles Associated with Nickel level in Urine.
AB  - Nickel (Ni) compounds are widely used in industrial and commercial products
      including household and cooking utensils, jewelry, dental appliances and
      implants. Occupational exposure to nickel is associated with an increased risk
      for lung and nasal cancers, is the most common cause of contact dermatitis and
      has an extensive effect on the immune system. The purpose of this study was two
      fold: (i) to evaluate immune response to the occupational exposure to nickel
      measured by the presence of anti-glycan antibodies (AGA) using a new biomarker
      discovery platform based on printed glycan arrays (PGA), and (ii) to evaluate and
      compile a sequence of bioinformatics and statistical methods which are
      specifically relevant to PGA-derived information and to identification of
      putative "Ni toxicity signature". The PGAs are similar to DNA microarrays, but
      contain deposits of various carbohydrates (glycans) instead of spotted DNAs. The
      study uses data derived from a set of 89 plasma specimens and their corresponding
      demographic information. The study population includes three subgroups: subjects
      directly exposed to Nickel that work in a refinery, subjects environmentally
      exposed to Nickel that live in a city where the refinery is located and subjects
      that live in a remote location. The paper describes the following sequence of
      nine data processing and analysis steps: (1) Analysis of inter-array
      reproducibility based on benchmark sera; (2) Analysis of intra-array
      reproducibility; (3) Screening of data - rejecting glycans which result in low
      intra-class correlation coefficient (ICC), high coefficient of variation and low
      fluorescent intensity; (4) Analysis of inter-slide bias and choice of data
      normalization technique; (5) Determination of discriminatory subsamples based on
      multiple bootstrap tests; (6) Determination of the optimal signature size
      (cardinality of selected feature set) based on multiple cross-validation tests;
      (7) Identification of the top discriminatory glycans and their individual
      performance based on nonparametric univariate feature selection; (8)
      Determination of multivariate performance of combined glycans; (9) Establishing
      the statistical significance of multivariate performance of combined glycan
      signature. The above analysis steps have delivered the following results: inter
      array reproducibility rho=0.920 +/- 0.030; intra-array reproducibility rho=0.929
      +/- 0.025; 249 out of 380 glycans passed the screening at ICC>80%, glycans in
      selected signature have ICC >= 88.7%; optimal signature size (after quantile
      normalization)=3; individual significance for the signature glycans p=0.00015 to
      0.00164, individual AUC values 0.870 to 0.815; observed combined performance for
      three glycans AUC=0.966, p=0.005, CI=[0.757, 0947]; specifity=94.4%,
      sensitivity=88.9%; predictive (cross-validated) AUC value 0.836.

PMID- 24737928
TI  - Anterior transarticular screw fixation for atlantoaxial arthrodesis: A report of
      two cases.
AB  - The sequelae of atlantoaxial instability (AAI) range from axial neck pain to life
      threatening neurologic injury. Instrumentation and fusion of the C1-2 joint is
      often indicated in the setting of clinical or biomechanical instability. This is
      the first clinical report of anterior Smith-Robinson C1-2 transarticular screw
      (TAS) fixation for AAI. The first patient presented with ischemic brain tissue
      secondary to post-traumatic C1-2 segment instability from a MVC 7 years prior to
      presentation. The second patient presented with a 3 year history of persistent
      right-sided neck and upper scalp pain. Both were treated with transarticular C1-2
      fusion through decortication of the atlantoaxial facet joints and TAS fixation
      via the anterior Smith-Robinson approach. At 16 months follow-up, the first
      patient maintained painless range of motion of the cervical spine and denied
      sensorimotor deficits. The second patient reported 90% improvement in her pre
      operative symptoms of neck pain and paresthesia. Anterior Smith-Robinson C1-2 TAS
      fixation provides a useful alternative to the posterior Goel and Magerl
      techniques for C1-2 stabilization and fusion. 

PMID- 24737929
TI  - Signal Processing and Machine Learning with Differential Privacy: Algorithms and
      challenges for continuous data.

PMID- 24737930
TI  - Nonlinear optical microscopy signal processing strategies in cancer.
AB  - This work reviews the most relevant present-day processing methods used to
      improve the accuracy of multimodal nonlinear images in the detection of
      epithelial cancer and the supporting stroma. Special emphasis has been placed on
      methods of non linear optical (NLO) microscopy image processing such as: second
      harmonic to autofluorescence ageing index of dermis (SAAID), tumor-associated
      collagen signatures (TACS), fast Fourier transform (FFT) analysis, and gray level
      co-occurrence matrix (GLCM)-based methods. These strategies are presented as a
      set of potential valuable diagnostic tools for early cancer detection. It may be
      proposed that the combination of NLO microscopy and informatics based image
      analysis approaches described in this review (all carried out on free software)
      may represent a powerful tool to investigate collagen organization and remodeling
      of extracellular matrix in carcinogenesis processes. 

PMID- 24737931
TI  - Revisiting the monoamine hypothesis of depression: a new perspective.
AB  - As the incidence of depression increases, depression continues to inflict
      additional suffering to individuals and societies and better therapies are
      needed. Based on magnetic resonance spectroscopy and laboratory findings, gamma
      aminobutyric acid (GABA) may be intimately involved in the pathophysiology of
      depression. The isoelectric point of GABA (pI = 7.3) closely approximates the pH
      of cerebral spinal fluid (CSF). This may not be a trivial observation as it may
      explain preliminary spectrophotometric, enzymatic, and HPLC data that monoamine
      oxidase (MAO) deaminates GABA. Although MAO is known to deaminate substrates such
      as catecholamines, indoleamines, and long chain aliphatic amines all of which
      contain a lipophilic moiety, there is very good evidence to predict that a low
      concentration of a very lipophilic microspecies of GABA is present when GABA pI =
      pH as in the CSF. Inhibiting deamination of this microspecies of GABA could
      explain the well-established successful treatment of refractory depression with
      MAO inhibitors (MAOI) when other antidepressants that target exclusively levels
      of monoamines fail. If further experimental work can confirm these preliminary
      findings, physicians may consider revisiting the use of MAOI for the treatment of
      non-intractable depression because the potential benefits of increasing GABA as
      well as the monoamines may outweigh the risks associated with MAOI therapy. 

PMID- 24737932
TI  - A Randomized Controlled Trial to Study the Effect of Yoga Therapy on Cardiac
      Function and N Terminal Pro BNP in Heart Failure.
AB  - AIMS: The purpose of this study was to evaluate whether yoga training in addition
      to standard medical therapy can improve cardiac function and reduce N terminal
      pro B-type natriuretic peptide (NT pro BNP) in heart failure (HF). METHODS: 130
      patients were recruited and randomized into two groups: Control Group (CG) (n =
      65), Yoga Group (YG). In YG, 44 patients and in CG, 48 patients completed the
      study. Cardiac function using left ventricular ejection fraction (LVEF),
      myocardial performance index (Tei index), and NT pro BNP, a biomarker of HF, was
      assessed at baseline and after 12 weeks. RESULT: Improvement in LVEF, Tei index,
      and NT pro BNP were statistically significant in both the groups. Furthermore,
      when the changes in before and after 12 weeks were in percentage, LVEF increased
      36.88% in the YG and 16.9% in the CG, Tei index was reduced 27.87% in the YG and
      2.79% in the CG, NT pro BNP was reduced 63.75% in the YG and 10.77% in the CG.
      The between group comparisons from pre to post 12 weeks were significant for YG
      improvements (LVEF, P < 0.01, Tei index, P < 0.01, NT pro BNP, P < 0.01).
      CONCLUSION: These results indicate that the addition of yoga therapy to standard
      medical therapy for HF patients has a markedly better effect on cardiac function
      and reduced myocardial stress measured using NT pro BNP in patients with stable
      HF.

PMID- 24737933
TI  - Overfeeding Dairy Cattle During Late-Pregnancy Alters Hepatic PPARalpha-Regulated
      Pathways Including Hepatokines: Impact on Metabolism and Peripheral Insulin
      Sensitivity.
AB  - Hepatic metabolic gene networks were studied in dairy cattle fed control (CON,
      1.34 Mcal/kg) or higher energy (overfed (OVE), 1.62 Mcal/kg) diets during the
      last 45 days of pregnancy. A total of 57 target genes encompassing PPARalpha
      targets/co-regulators, hepatokines, growth hormone (GH)/insulin-like growth
      factor 1 (IGF-1) axis, lipogenesis, and lipoprotein metabolism were evaluated on 
      14, 7, 14, and 30 days around parturition. OVE versus CON cows were in more
      negative energy balance (NEB) postpartum and had greater serum non-esterified
      fatty acids (NEFA), beta-hydroxybutyrate (BHBA), and liver triacylglycerol (TAG)
      concentrations. Milk synthesis rate did not differ. Liver from OVE cows responded
      to postpartal NEB by up-regulating expression of PPARalpha-targets in the fatty
      acid oxidation and ketogenesis pathways, along with gluconeogenic genes.
      Hepatokines (fibroblast growth factor 21 (FGF21), angiopoietin-like 4 (ANGPTL4))
      and apolipoprotein A-V (APOA5) were up-regulated postpartum to a greater extent
      in OVE than CON. OVE led to greater blood insulin prepartum, lower NEFA:insulin,
      and greater lipogenic gene expression suggesting insulin sensitivity was not
      impaired. A lack of change in APOB, MTTP, and PNPLA3 coupled with upregulation of
      PLIN2 postpartum in cows fed OVE contributed to TAG accumulation. Postpartal
      responses in NEFA and FGF21 with OVE support a role of this hepatokine in
      diminishing adipose insulin sensitivity. 

PMID- 24737934
TI  - Diagnosis of a Nonpalpable Intraductal Papilloma without Radiological Abnormality
      by Nipple Discharge Smear Examination: A Case Report.
AB  - Nipple discharge is the third most common breast complaint after breast pain and
      breast mass, most commonly associated with endocrine alterations and/or
      medications, pregnancy, lactation, post lactation, fibrocystic disease,
      intraductal papilloma, duct ectasia, nipple adenoma, infection, chronic mastitis,
      subareolar abscess, and least frequently, breast carcinoma. Cytological
      examination of nipple discharge (ND) is a noninvasive method of diagnosing the
      underlying breast pathology. We report a 46 year old female, who presented with
      pain and blood-mixed ND from the right breast with an impalpable mass.
      Cytological examination of the discharge was done and diagnosis of papillary
      neoplasm with degeneration, metaplasia, and atypia was given, which was further
      confirmed on histology and positive IHC for HMWCK and p63. Final diagnosis was
      intraductal papilloma of the lactiferous duct with squamous metaplasia and
      infarction. Differentiating benign papilloma from a carcinoma is challenging to
      the cytopathologist and requires clinicopathological correlation and a good
      knowledge of cytology. 

PMID- 24737935
TI  - Temporal- and Location-Specific Alterations of the GABA Recycling System in Mecp2
      KO Mouse Brains.
AB  - Rett syndrome (RTT), associated with mutations in methyl-CpG-binding protein 2
      (Mecp2), is linked to diverse neurological symptoms such as seizures, motor
      disabilities, and cognitive impairments. An altered GABAergic system has been
      proposed as one of many underlying pathologies of progressive neurodegeneration
      in several RTT studies. This study for the first time investigated the temporal-
      and location-specific alterations in the expression of gamma-amino butyric acid
      (GABA) transporter 1 (GAT-1), vesicular GABA transporter (vGAT), and glutamic
      acid decarboxylase 67kD (GAD67) in wild type (WT) and knockout (KO) mice in the
      Mecp2(tm1.1Bird/y) mouse model of RTT. Immunohistochemistry (IHC) co-labeling of
      GAT-1 with vGAT identified GABAergic synapses that were quantitated for mid
      sagittal sections in the frontal cortex (FC), hippocampal dentate gyrus (DG), and
      striatum (Str). An age-dependent increase in the expression of synaptic GABA
      transporters, GAT-1, and vGAT, was observed in the FC and DG in WT brains. Mecp2
      KO mice showed a significant alteration in this temporal profile that was
      location-specific, only in the FC. GAD67-positive cell densities also showed an
      age-dependent increase in the FC, but a decrease in the DG in WT mice. However,
      these densities were not significantly altered in the KO mice in the regions
      examined in this study. Therefore, the significant location-specific
      downregulation of synaptic GABA transporters in Mecp2 KO brains with unaltered
      densities of GAD67-positive interneurons may highlight the location-specific
      synaptic pathophysiology in this model of RTT. 

PMID- 24737938
TI  - Therapeutic Approaches for Inhibition of Protein Aggregation in Huntington's
      Disease.
AB  - Huntington's disease (HD) is a late-onset and progressive neurodegenerative
      disorder that is caused by aggregation of mutant huntingtin protein which
      contains expanded-polyglutamine. The molecular chaperones modulate the
      aggregation in early stage and known for the most potent protector of
      neurodegeneration in animal models of HD. Over the past decades, a number of
      studies have demonstrated molecular chaperones alleviate the pathogenic symptoms
      by polyQ-mediated toxicity. Moreover, chaperone-inducible drugs and anti
      aggregation drugs have beneficial effects on symptoms of disease. Here, we focus
      on the function of molecular chaperone in animal models of HD, and review the
      recent therapeutic approaches to modulate expression and turn-over of molecular
      chaperone and to develop anti-aggregation drugs. 

PMID- 24737937
TI  - Disturbance of the glutamatergic system in mood disorders.
AB  - The role of glutamatergic system in the neurobiology of mood disorders draws
      increasing attention, as disturbance of this system is consistently implicated in
      mood disorders including major depressive disorder and bipolar disorder. Thus,
      the glutamate hypothesis of mood disorders is expected to complement and improve
      the prevailing monoamine hypothesis, and may indicate novel therapeutic targets.
      Since the contribution of astrocytes is found to be crucial not only in the
      modulation of the glutamatergic system but also in the maintenance of brain
      energy metabolism, alterations in the astrocytic function and neuroenergetic
      environment are suggested as the potential neurobiological underpinnings of mood
      disorders. In the present review, the evidence of glutamatergic abnormalities in
      mood disorders based on postmortem and magnetic resonance spectroscopy (MRS)
      studies is presented, and disrupted energy metabolism involving astrocytic
      dysfunction is proposed as the underlying mechanism linking altered energy
      metabolism, perturbations in the glutamatergic system, and pathogenesis of mood
      disorders. 

PMID- 24737936
TI  - Cerebral lateralization of pro- and anti-social tendencies.
AB  - Mounting evidence suggest that the right-hemisphere (RH) has a relative
      advantage, over the left-hemisphere (LH), in mediating social intelligence -
      identifying social stimuli, understanding the intentions of other people,
      awareness of the dynamics in social relationships, and successful handling of
      social interactions. Furthermore, a review and synthesis of the literature
      suggest that pro-social attitudes and behaviors are associated with physiological
      activity in the RH, whereas unsocial and anti-social tendencies are mediated
      primarily by the LH. This hemispheric asymmetry is rooted in several
      neurobiological and functional differences between the two hemispheres. (I)
      Positive social interactions often require inhibiting one's immediate desires and
      considering the perspectives and needs of others. Given that self-control is
      mediated by the RH, pro-social emotions and behaviors are, therefore, inherently
      associated with the RH as it subserves the brain's self-restraint mechanisms.
      (II) The RH mediates experiences of vulnerability. It registers the relative
      clumsiness and motor weakness of the left limbs, and it is involved, more than
      the LH, in processing threats and mediating fear. Emotional states of
      vulnerability trigger the need for affiliation and sociality, therefore the RH
      has a greater role in mediating pro-social attitudes and behaviors. (III) The RH
      mediates a holistic mode of representing the world. Holistic perception
      emphasizes similarities rather than differences, takes a long-term perspective,
      is associated with divergent thinking and seeing other points-of-view, and it
      mediates a personal mode of relating to people. All these features of holistic
      perception facilitate a more empathetic attitude toward others and pro-social
      behaviors. 

PMID- 24737939
TI  - Alzheimer's disease and stem cell therapy.
AB  - The loss of neuronal cells in the central nervous system may occur in many
      neurodegenerative diseases. Alzheimer's disease is a common senile disease in
      people over 65 years, and it causes impairment characterized by the decline of
      mental function, including memory loss and cognitive impairment, and affects the
      quality of life of patients. However, the current therapeutic strategies against
      AD are only to relieve symptoms, but not to cure it. Because there are only a few
      therapeutic strategies against Alzheimer's disease, we need to understand the
      pathogenesis of this disease. Cell therapy may be a powerful tool for the
      treatment of Alzheimer's disease. This review will discuss the characteristics of
      Alzheimer's disease and various available therapeutic strategies. 

PMID- 24737940
TI  - Attenuated Glial K(+) Clearance Contributes to Long-Term Synaptic Potentiation
      Via Depolarizing GABA in Dorsal Horn Neurons of Rat Spinal Cord.
AB  - It has been reported that long-term enhancement of superficial dorsal horn (DHs)
      excitatory synaptic transmission underlies central sensitization, secondary
      hyperalgesia, and persistent pain. We tested whether impaired clearance of K(+)
      and glutamate by glia in DHs may contribute to initiation and maintenance of the
      CNS pain circuit and sensorimotor abnormalities. Transient exposure of the spinal
      cord slice to fluorocitrate (FC) is shown to be accompanied by a protracted
      decrease of the DHs optical response to repetitive electrical stimulation of the
      ipsilateral dorsal root, and by a similarly protracted increase in the
      postsynaptic response of the DHs like LTP. It also is shown that LTPFC does not
      occur in the presence of APV, and becomes progressively smaller as [K(+)]o in the
      perfusion solution decreased from 3.0 mM to 0.0 mM. Interestingly LTPFC is
      reduced by bath application of Bic. Whole-cell patch recordings were carried out
      to evaluate the effects of FC on the response of DHs neurons to puffer-applied
      GABA. The observations reveal that transient exposure to FC is reliably
      accompanied by a prolonged (>1 hr) depolarizing shift of the equilibrium
      potential for the DHs neuron transmembrane ionic currents evoked by GABA.
      Considered collectively, the findings demonstrate that LTPFC involves (1)
      elevation of [K(+)]o in the DHs, (2) NMDAR activation, and (3) conversion of the
      effect of GABA on DHs neurons from inhibition to excitation. It is proposed that
      a transient impairment of astrocyte energy production can trigger the cascade of
      dorsal horn mechanisms that underlies hyperalgesia and persistent pain. 

PMID- 24737941
TI  - Tumor Necrosis Factor-Associated Protein 1 (TRAP1) is Released from the
      Mitochondria Following 6-hydroxydopamine Treatment.
AB  - Parkinson's disease (PD) is a common neurodegenerative disorder characterized by
      progressive degeneration of dopaminergic neurons in the substantia nigra pars
      compacta. Most cases are sporadic and its etiology is incompletely understood.
      However, increasing evidence suggests that oxidative stress and mitochondrial
      dysfunction may be involved in the pathogenesis of Parkinson's disease. The aim
      of this study was to investigate changes in mitochondrial protein profiles during
      dopaminergic neuronal cell death using two-dimensional gel electrophoresis in
      conjunction with mass spectrometry. Several protein spots were found to be
      significantly altered following treatment of MN9D dopaminergic neuronal cells
      with 6-hydroxydopamine (6-OHDA). Among several identified candidates, TNF
      receptor-associated protein 1 (TRAP1), a mitochondrial molecular chaperone, was
      released from the mitochondria into the cytosol in MN9D cells as well as primary
      cultures of dopaminergic neurons following 6-OHDA treatment. This event was drug
      specific in that such apoptotic inducers as staurosporine and etoposide did not
      cause translocation of TRAP1 into the cytosol. To our knowledge, the present
      study is the first to demonstrate the drug-induced subcellular translocation of
      TRAP1 during neurodegeneration. Further studies delineating cellular mechanism
      associated with this phenomenon and its functional consequence may provide better
      understanding of dopaminergic neurodegeneration that underlies PD pathogenesis. 

PMID- 24737942
TI  - Mesenchymal stem cells improved the ultrastructural morphology of cerebral
      tissues after subarachnoid hemorrhage in rats.
AB  - Subarachnoid hemorrhage (SAH) causes widespread disruption in the cerebral
      architecture.The process of SAH is complicated and many people lose their lives
      or become disabled after injury. Mesenchymal stem cells (MSCs) are considered as
      good candidate for repair of cerebral damage. The aim was to assess the
      ultrastructural changes in the rat cerebral tissue after intravenous
      transplantation of MSCs. Female Wistar rats (8 per group) weighing 275~300 g were
      assigned to control (SAH+PBS) and experimental groups (SAH+MSCs).The samples from
      middle cerebral arterial wall and parietal cerebral tissue were prepared for
      transmission electron microscopy (TEM) according to standard protocol. Fine
      architectures of the vessel wall, including the contraction of the inner layer,
      smooth muscle layer,as well as neural cells were observed after SAH. Cerebral
      arterial wall and cortex, including neuronal and glial cells were injured post
      SAH. But, administration of MSCs improved the structural integrity of cerebral
      tissues. Changes were much more balanced with their relative improvement in some
      areas. The role of MSCs for repairing the injured cerebral tissues post
      experimental SAH was approved by electron microscopy. 

PMID- 24737943
TI  - Melittin ameliorates the inflammation of organs in an amyotrophic lateral
      sclerosis animal model.
AB  - Amyotrophic lateral sclerosis (ALS) is a devastating progressive
      neurodegenerative disorder characterized by a selective loss of motor neurons in
      the spinal cord, brainstem, and motor cortex, leading to weakness of the limb and
      bulbar muscles. Although the immediate cause of death in ALS is the destruction
      of motor neurons, ALS is a multi-organ disease that also affects the lungs,
      spleen, and liver. Melittin is one of components of bee venom and has anti
      neuroinflammatory effects in the spinal cord, as shown in an ALS animal model. To
      investigate the effects of melittin on inflammation in the lungs and spleen, we
      used hSOD1(G93A) transgenic mice that are mimic for ALS. Melittin treatment
      reduced the expression of inflammatory proteins, including Iba-1 and CD14 by 1.9-
      and 1.3-fold (p<0.05), respectively, in the lungs of symptomatic hSOD1(G93A)
      transgenic mice. In the spleen, the expression of CD14 and COX2 that are related
      to inflammation were decreased by 1.4 fold (p<0.05) and cell survival proteins
      such as pERK and Bcl2 were increased by 1.3- and 1.5-fold (p<0.05) in the
      melittin-treated hSOD1G93A transgenic mice. These findings suggest that melittin
      could be a candidate to regulate the immune system in organs affected by ALS. 

PMID- 24737944
TI  - Glutathione protects brain endothelial cells from hydrogen peroxide-induced
      oxidative stress by increasing nrf2 expression.
AB  - Glutathione (GSH) protects cells against oxidative stress by playing an
      antioxidant role. Protecting brain endothelial cells under oxidative stress is
      key to treating cerebrovascular diseases and neurodegenerative diseases including
      Alzheimer's disease and Huntington's disease. In present study, we investigated
      the protective effect of GSH on brain endothelial cells against hydrogen peroxide
      (H2O2). We showed that GSH attenuates H2O2-induced production of nitric oxide
      (NO), reactive oxygen species (ROS), and 8-Oxo-2'-deoxyguanosine (8-OHdG), an
      oxidized form of deoxiguanosine. GSH also prevents H2O2-induced reduction of
      tight junction proteins. Finally, GSH increases the level of nuclear factor
      erythroid 2-related factor 2 (Nrf2) and activates Nrf2-mediated signaling
      pathways. Thus, GSH is a promising target to protect brain endothelial cells in
      conditions of brain injury and disease. 

PMID- 24737945
TI  - A method for generating a mouse model of stroke: evaluation of parameters for
      blood flow, behavior, and survival [corrected].
AB  - Stroke is one of the common causes of death and disability. Despite extensive
      efforts in stroke research, therapeutic options for improving the functional
      recovery remain limited in clinical practice. Experimental stroke models using
      genetically modified mice could aid in unraveling the complex pathophysiology
      triggered by ischemic brain injury. Here, we optimized the procedure for
      generating mouse stroke model using an intraluminal suture in the middle cerebral
      artery and verified the blockage of blood flow using indocyanine green coupled
      with near infra-red radiation. The first week after the ischemic injury was
      critical for survivability. The survival rate of 11% in mice without any
      treatment but increased to 60% on administering prophylactic antibiotics. During
      this period, mice showed severe functional impairment but recovered spontaneously
      starting from the second week onward. Among the various behavioral tests, the
      pole tests and neurological severity score tests remained reliable up to 4 weeks
      after ischemia, whereas the rotarod and corner tests became less sensitive for
      assessing the severity of ischemic injury with time. Further, loss of body weight
      was also observed for up 4 weeks after ischemia induction. In conclusion, we have
      developed an improved approach which allows us to investigate the role of the
      cell death-related genes in the disease progression using genetically modified
      mice and to evaluate the modes of action of candidate drugs. 

PMID- 24737946
TI  - Synovial chondrosarcoma arising in synovial chondromatosis.
AB  - Primary synovial chondromatosis (SC) is a rare proliferative disorder that causes
      pain, swelling, and restriction of movement to the joints it affects. The disease
      frequently runs a protracted course, often requiring multiple surgical procedures
      to obtain some control. Few reports exist detailing the natural history of SC,
      although malignant transformation to synovial chondrosarcoma (CHS) is recognized
      to be a rare event. The aim of our study was to review a large orthopaedic
      oncology database in order to evaluate the incidence of CHS arising from SC. We
      identified 78 patients who have presented to our centre with primary synovial
      chondromatosis (SC). Of those patients, 5 went on to develop malignant change.
      This represents a 6.4% incidence of developing synovial chondrosarcoma (CHS)
      within preexisting primary synovial chondromatosis. The patients had a mean age
      of 28 years at first diagnosis with synovial chondromatosis with the median time
      from original diagnosis to malignant transformation being 20 years (range 2.7-39
      yrs). 

PMID- 24737947
TI  - Semiparametric Inference for Data with a Continuous Outcome from a Two-Phase
      Probability Dependent Sampling Scheme.
AB  - Multi-phased designs and biased sampling designs are two of the well recognized
      approaches to enhance study efficiency. In this paper, we propose a new and cost
      effective sampling design, the two-phase probability dependent sampling design
      (PDS), for studies with a continuous outcome. This design will enable
      investigators to make efficient use of resources by targeting more informative
      subjects for sampling. We develop a new semiparametric empirical likelihood
      inference method to take advantage of data obtained through a PDS design.
      Simulation study results indicate that the proposed sampling scheme, coupled with
      the proposed estimator, is more efficient and more powerful than the existing
      outcome dependent sampling design and the simple random sampling design with the
      same sample size. We illustrate the proposed method with a real data set from an
      environmental epidemiologic study.

PMID- 24737948
TI  - Synthesis and solid-state structures of a macrocyclic receptor based on the 2,6
      bis(2-anilinoethynyl)pyridine scaffold.
AB  - A fluorescent macrocyclic anion receptor based on the 2,6-bis(2
      anilinoethynyl)pyridine scaffold has been synthesized to investigate the
      mechanism of fluorescence quenching in this class of compounds. X-ray
      crystallography reveals that the binding pocket of the receptor is a natural host
      to both H2O and HCl, accommodating either molecule in nearly identical
      environments. Our studies show that protonation, not collisional quenching, is
      responsible for the observed fluorescence quenching response.

PMID- 24737949
TI  - BRAF and beyond: Tailoring strategies for the individual melanoma patient.
AB  - Until recently, options for therapy in metastatic melanoma were limited. The
      understanding of immune check-point blockade and the discovery of molecular
      pathways involving driver mutations like BRAF has transformed the therapeutic
      landscape in this disease. Ipilimumab was the first drug shown to improve
      survival while vemurafenib demonstrated rapid responses never seen before in
      melanoma. Drugs from these classes and others are now in advanced stages of
      development and primed to positively impact patient survival in an incremental
      fashion. In this review, we highlight some of the developments during this
      renaissance in melanoma therapy and discuss agents of promise. Clinical
      challenges we face include individualizing therapy for patients, overcoming
      resistance to molecularly targeted therapy and developing rationale combinations
      or sequences of drugs. A concerted bench and bedside effort in this direction
      will undoubtedly keep melanoma in the forefront in an era of personalized
      medicine. 

PMID- 24737950
TI  - Antisense oligonucleotides directed against insulin-like growth factor-II
      messenger ribonucleic acids delay the progress of rat hepatocarcinogenesis.
AB  - BACKGROUND: Hepatocellular carcinoma (HCC) is a multistep complex process, caused
      by many of genetic alteration. Insulin-like growth factors and their receptor
      have been widely implicated to HCC. Insulin-like growth factor-II (IGF-II) is a
      mitogenic polypeptide, found in various fetal and neonatal tissues of humans and
      rats and expresses in HCC. Here we investigated anticancer potential of
      phosphorothioate antisense oligonucleotides (ASOs) against three coding exons
      (exon-1/exon-2/exon-3) of IGF-II messenger ribonucleic acid in rat
      hepatocarcinogenesis model. MATERIALS AND METHODS: During diethylnitrosamine and
      2-acetylaminofluorene induced hepatocarcinogenesis, rats were treated with ASOs.
      Various biochemical and histological studies were conducted. RESULTS: About 40%
      of carcinogen treated rats, which received two oligomers (against exon-1 or-3)
      did not show any hepatic lesion, hyperplastic nodule or tumor and remaining 60%
      of those rats showed lesion incidence and had about 59% and 55% reductions in the
      numbers of hepatic altered foci, respectively. Reductions in the total lesion
      area when compared with carcinogen control rats were 64% and 53%, respectively
      for the animals treated with carcinogen and received the ASOs against exon-1/-3.
      Fluorescein isothiocyanate-labeled ASO reached in the hepatocytes in 2 h. No
      predominant IGF-II overexpression was observed in case of rats treated with the
      two ASOs. Treatment of the antisense IGF-II oligomers in carcinogen treated rats
      show better hepatocellular integrity along with several preneoplastic/neoplastic
      marker isoenzyme/enzyme modulations. CONCLUSIONS: Two of the three antisense
      oligomer-types effectively controlled IGF-II overexpression, causing the delay of
      the development and/or progress of hepatic cancer in rats.

PMID- 24737951
TI  - Targeted therapy for renal cell carcinoma: The next lap.
AB  - Advances in rationally targeted therapeutics over the last decade have
      transformed the clinical care of advanced kidney cancer. While oncologists
      consolidate the gains of the wave of new agents, comprising a panoply of anti
      vascular endothelial growth factor multi-targeted tyrosine kinase inhibitors and
      inhibitors of the mammalian target of rapamycin (mTOR), there is an increasing
      sense that a plateau has been reached in the short term. It is sobering that all
      currently approved targeted therapies have not yielded durable remissions and
      remain palliative in intent. In the context of recent insights in kidney cancer
      biology, we review promising ongoing and future approaches for kidney cancer
      therapeutics aimed toward forging new paths in the systemic management of renal
      cell carcinoma. Broadly, candidate agents for such innovative strategies include
      immune check-point inhibitors, anti-cancer stem cell agents, next-generation anti
      vascular endothelial growth factor receptor and anti-mTOR agents as well as more
      investigational agents in the preclinical and early clinical development
      settings. 

PMID- 24737952
TI  - Targeted therapy in gastrointestinal malignancies.
AB  - Increased understanding of cancer pathogenesis has identified several pathways
      that serve as potential targets for novel targeted agents in development. The
      selection of targeted cancer therapy based on biomarkers has instigated a new era
      of personalized medicine and changed the way we practice oncology. Many targeted
      agents are approved for treatment of gastrointestinal malignancies most targeting
      tumor angiogenesis, and many more are in different phases of development. Here we
      briefly summarize nine different targeted agents that are approved currently in
      the U.S. and several other agents currently being studied in various
      gastrointestinal cancers. 

PMID- 24737953
TI  - Expression profiling using a cDNA array and immunohistochemistry for the
      extracellular matrix genes FN-1, ITGA-3, ITGB-5, MMP-2, and MMP-9 in colorectal
      carcinoma progression and dissemination.
AB  - Colorectal cancer dissemination depends on extracellular matrix genes related to
      remodeling and degradation of the matrix structure. This investigation intended
      to evaluate the association between FN-1, ITGA-3, ITGB-5, MMP-2, and MMP-9 gene
      and protein expression levels in tumor tissue with clinical and histopathological
      neoplastic parameters of cancer dissemination. The expression associations
      between ECM molecules and selected epithelial markers EGFR, VEGF, Bcl2, P53, and
      KI-67 have also been examined in 114 patients with colorectal cancer who
      underwent primary tumor resection. Quantitative real-time PCR and
      immunohistochemistry tissue microarray methods were performed in samples from the
      primary tumors. The gene expression results showed that the ITGA-3 and ITGB-5
      genes were overexpressed in tumors with lymph node and distant metastasis (III/IV
      stage tumors compared with I/II tumors). The MMP-2 gene showed significant
      overexpression in mucinous type tumors, and MMP-9 was overexpressed in villous
      adenocarcinoma histologic type tumors. The ECM genes MMP9 and ITGA-3 have shown a
      significant expression correlation with EGFR epithelial marker. The
      overexpression of the matrix extracellular genes ITGA-3 and ITGB-5 is associated
      with advanced stage tumors, and the genes MMP-2 and MMP-9 are overexpressed in
      mucinous and villous adenocarcinoma type tumors, respectively. The epithelial
      marker EGFR overactivity has been shown to be associated with the ECM genes MMP-9
      and ITGA-3 expression. 

PMID- 24737954
TI  - Influence of pre- and postharvest summer pruning on the growth, yield, fruit
      quality, and carbohydrate content of early season peach cultivars.
AB  - Winter and summer pruning are widely applied processes in all fruit trees,
      including in peach orchard management. This study was conducted to determine the
      effects of summer prunings (SP), as compared to winter pruning (WP), on shoot
      length, shoot diameter, trunk cross sectional area (TCSA) increment, fruit yield,
      fruit quality, and carbohydrate content of two early ripening peach cultivars
      ("Early Red" and "Maycrest") of six years of age, grown in semiarid climate
      conditions, in 2008 to 2010. The trees were grafted on GF 677 rootstocks, trained
      with a central leader system, and spaced 5 * 5 m apart. The SP carried out after
      harvesting in July and August decreased the shoot length significantly; however,
      it increased its diameter. Compared to 2009, this effect was more marked in year
      2010. In general, control and winter pruned trees of both cultivars had the
      highest TCSA increment and yield efficiency. The SP increased the average fruit
      weight and soluble solids contents (SSC) more than both control and WP. The
      titratable acidity showed no consistent response to pruning time. The
      carbohydrate accumulation in shoot was higher in WP and in control than in SP
      trees. SP significantly affected carbohydrate accumulation; postharvest pruning
      showed higher carbohydrate content than preharvest pruning. 

PMID- 24737956
TI  - A novel macroblock level rate control method for stereo video coding.
AB  - To compress stereo video effectively, this paper proposes a novel macroblock (MB)
      level rate control method based on binocular perception. A binocular just
      notification difference (BJND) model based on the parallax matching is first used
      to describe binocular perception. Then, the proposed rate control method is
      performed in stereo video coding with four levels, namely, view level, group-of
      pictures (GOP) level, frame level, and MB level. In the view level, different
      proportions of bitrates are allocated for the left and right views of stereo
      video according to the prestatistical rate allocation proportion. In the GOP
      level, the total number of bitrates allocated to each GOP is computed and the
      initial quantization parameter of each GOP is set. In the frame level, the target
      bits allocated to each frame are computed. In the MB level, visual perception
      factor, which is measured by the BJND value of MB, is used to adjust the MB level
      bit allocation, so that the rate control results in line with the human visual
      characteristics. Experimental results show that the proposed method can control
      the bitrate more accurately and get better subjective quality of stereo video,
      compared with other methods. 

PMID- 24737957
TI  - A new mixed element method for a class of time-fractional partial differential
      equations.
AB  - A kind of new mixed element method for time-fractional partial differential
      equations is studied. The Caputo-fractional derivative of time direction is
      approximated by two-step difference method and the spatial direction is
      discretized by a new mixed element method, whose gradient belongs to the simple
      (L (2)(Omega)(2)) space replacing the complex H(div; Omega) space. Some a priori
      error estimates in L (2)-norm for the scalar unknown u and in (L (2))(2)-norm for
      its gradient sigma. Moreover, we also discuss a priori error estimates in H (1)
      norm for the scalar unknown u. 

PMID- 24737958
TI  - A cloud-based X73 ubiquitous mobile healthcare system: design and implementation.
AB  - Based on the user-centric paradigm for next generation networks, this paper
      describes a ubiquitous mobile healthcare (uHealth) system based on the ISO/IEEE
      11073 personal health data (PHD) standards (X73) and cloud computing techniques.
      A number of design issues associated with the system implementation are outlined.
      The system includes a middleware on the user side, providing a plug-and-play
      environment for heterogeneous wireless sensors and mobile terminals utilizing
      different communication protocols and a distributed "big data" processing
      subsystem in the cloud. The design and implementation of this system are
      envisaged as an efficient solution for the next generation of uHealth systems. 

PMID- 24737955
TI  - Xenoimplantation of an extracellular-matrix-derived, biphasic, cell-scaffold
      construct for repairing a large femoral-head high-load-bearing osteochondral
      defect in a canine model.
AB  - This study was aimed to develop an ECM-derived biphasic scaffold and to
      investigate its regeneration potential loaded with BM-MSCs in repair of large,
      high-load-bearing osteochondral defects of the canine femoral head. The scaffolds
      were fabricated using cartilage and bone ECM as a cartilage and bone layer,
      respectively. Osteochondral constructs were fabricated using induced BM-MSCs and
      the scaffold. Osteochondral defects (11 mm diameter * 10 mm depth) were created
      on femoral heads of canine and treated with the constructs. The repaired tissue
      was evaluated for gross morphology, radiography, histological, biomechanics at 3
      and 6 months after implantation. Radiography revealed that femoral heads slightly
      collapsed at 3 months and severely collapsed at 6 months. Histology revealed that
      some defects in femoral heads were repaired, but with fibrous tissue or
      fibrocartilage, and femoral heads with different degrees of collapse. The bone
      volume fraction was lower for subchondral bone than normal femoral bone at 3 and
      6 months. Rigidity was lower in repaired subchondral bone than normal femoral
      bone at 6 months. The ECM-derived, biphasic scaffold combined with induced BM
      MSCs did not successfully repair large, high-load-bearing osteochondral defects
      of the canine femoral head. However, the experience can help improve the
      technique of scaffold fabrication and vascularization.

PMID- 24737959
TI  - Sequence characterization and spatiotemporal expression patterns of PbS26-RNase
      gene in Chinese White Pear (Pyrus bretschneideri).
AB  - Many flowering plants exhibit an important intraspecific reproductive barrier
      phenomenon, that is, self-incompatibility (SI), in which S-RNase genes play a
      significant role. To clarify the specific function of S-RNase genes in Chinese
      pears, the full length cDNA of PbS 26 -RNase was isolated by rapid amplification
      of cDNA ends (RACE) technology from Chinese white pear (Pyrus bretschneideri)
      cultivar "Hongpisu." The cDNA sequence for PbS 26 -RNase was deposited in GenBank
      under accession number EU081888. At the amino acid level, the PbS 26 -RNase
      displayed the highest similarity (96.9%) with PcSa-RNase of P. communis, and only
      seven amino acid differences were present in the two S-RNases. Phylogenetic
      analysis of rosaceous S-RNases indicated that the PbS 26 -RNase clustered with
      maloideous S-RNases, forming a subfamily-specific not a species-specific group.
      The PbS 26 -RNase gene was specifically expressed in the style but not other
      tissues/organs. The expression level of the PbS 26 -RNase gene rapidly increased
      at bell balloon stage (BBS), and then it dropped after pollination. However, the
      abundance of the PbS 26 -RNase gene transcript in the style was greater after
      cross-pollination than after self-pollination. In addition, a method for rapidly
      detecting the PbS 26 -RNase gene was developed via allele-specific primers
      design. The present study could provide a scientific basis for fully clarifying
      the mechanism of pear SI at the molecular level. 

PMID- 24737960
TI  - Contractive maps in locally transitive relational metric spaces.
AB  - Some fixed point results are given for a class of Meir-Keeler contractive maps
      acting on metric spaces endowed with locally transitive relations. Technical
      connections with the related statements due to Berzig et al. (2014) are also
      being discussed. 

PMID- 24737961
TI  - Condition assessment of PC tendon duct filling by elastic wave velocity mapping.
AB  - Imaging techniques are high in demand for modern nondestructive evaluation of
      large-scale concrete structures. The travel-time tomography (TTT) technique,
      which is based on the principle of mapping the change of propagation velocity of
      transient elastic waves in a measured object, has found increasing application
      for assessing in situ concrete structures. The primary aim of this technique is
      to detect defects that exist in a structure. The TTT technique can offer an
      effective means for assessing tendon duct filling of prestressed concrete (PC)
      elements. This study is aimed at clarifying some of the issues pertaining to the
      reliability of the technique for this purpose, such as sensor arrangement, model,
      meshing, type of tendon sheath, thickness of sheath, and material type as well as
      the scale of inhomogeneity. The work involved 2D simulations of wave motions,
      signal processing to extract travel time of waves, and tomography reconstruction
      computation for velocity mapping of defect in tendon duct. 

PMID- 24737962
TI  - Prediction based proactive thermal virtual machine scheduling in green clouds.
AB  - Cloud computing has rapidly emerged as a widely accepted computing paradigm, but
      the research on Cloud computing is still at an early stage. Cloud computing
      provides many advanced features but it still has some shortcomings such as
      relatively high operating cost and environmental hazards like increasing carbon
      footprints. These hazards can be reduced up to some extent by efficient
      scheduling of Cloud resources. Working temperature on which a machine is
      currently running can be taken as a criterion for Virtual Machine (VM)
      scheduling. This paper proposes a new proactive technique that considers current
      and maximum threshold temperature of Server Machines (SMs) before making
      scheduling decisions with the help of a temperature predictor, so that maximum
      temperature is never reached. Different workload scenarios have been taken into
      consideration. The results obtained show that the proposed system is better than
      existing systems of VM scheduling, which does not consider current temperature of
      nodes before making scheduling decisions. Thus, a reduction in need of cooling
      systems for a Cloud environment has been obtained and validated. 

PMID- 24737964
TI  - Simulating a measurement of the 2nd knee in the cosmic ray spectrum with an
      atmospheric fluorescence telescope tower array.
AB  - A fluorescence telescope tower array has been designed to measure cosmic rays in
      the energy range of 10(17)-10(18) eV. A full Monte Carlo simulation, including
      air shower production, light generation and propagation, detector response,
      electronics, and trigger system, has been developed for that purpose. Using such
      a simulation tool, the detector configuration, which includes one main tower
      array and two side-trigger arrays, 24 telescopes in total, has been optimized.
      The aperture and the event rate have been estimated. Furthermore, the performance
      of the X max technique in measuring composition has also been studied.

PMID- 24737965
TI  - Real-time depth-based hand detection and tracking.
AB  - This paper illustrates the hand detection and tracking method that operates in
      real time on depth data. To detect a hand region, we propose the classifier that
      combines a boosting and a cascade structure. The classifier uses the features of
      depth-difference at the stage of detection as well as learning. The features of
      each candidate segment are to be computed by subtracting the averages of depth
      values of subblocks from the central depth value of the segment. The features are
      selectively employed according to their discriminating power when constructing
      the classifier. To predict a hand region in a successive frame, a seed point in
      the next frame is to be determined. Starting from the seed point, a region
      growing scheme is applied to obtain a hand region. To determine the central point
      of a hand, we propose the so-called Depth Adaptive Mean Shift algorithm. DAM
      Shift is a variant of CAM-Shift (Bradski, 1998), where the size of the search
      disk varies according to the depth of a hand. We have evaluated the proposed hand
      detection and tracking algorithm by comparing it against the existing AdaBoost
      (Friedman et al., 2000) qualitatively and quantitatively. We have analyzed the
      tracking accuracy through performance tests in various situations. 

PMID- 24737963
TI  - Sialometry of upper labial minor glands: a clinical approach by the use of
      weighing method Schirmer's test strips paper.
AB  - OBJECTIVES: To establish referential values ranges of hyposalivation and
      normosalivation for the salivary flow rate (SFR) of upper labial (LS) and palatal
      (PS) mucosa using Schirmer's test strips paper and as a second goal to determine
      the values ranges of the SFR of palatal (PS) and upper labial (LS) mucosa in
      subjects with and without xerostomia. METHODS: A cross-sectional study was
      conducted among subjects distributed in three groups according to their
      unstimulated and stimulated whole saliva. RESULTS: 144 subjects were enrolled in
      groups as follows: severe hyposalivation (n = 24), mild hyposalivation (n = 78),
      and normosalivation (n = 42). The mean and the 95% confidence interval for the LS
      flow rate ( MU L/cm(2)/min) were 3.2 (2.46 to 3.94), 5.86 (4.96 to 6.75), and
      9.08 (7.63 to 10.53) (P < 0.001) for each group, respectively. The PS results
      were 1.01 (0.68 to 1.34), 1.72 (1.31 to 2.13), and 2.44 (1.66 to 3.22) (P =
      0.014). Xerostomia complainers presented lower rates of LS (5.17 (4.06 to 6.23))
      than non-complainers (7.33 (6.4 to 8.27)) (P = 0.003). CONCLUSIONS: The test was
      reliable to provide referential values ranges for LS flow rate measurement and
      was shown to be valid to distinguish normosalivation from severe and mild
      hyposalivation and also to predict xerostomia.

PMID- 24737966
TI  - Numerical absorbing boundary conditions based on a damped wave equation for
      pseudospectral time-domain acoustic simulations.
AB  - In the context of wave-like phenomena, Fourier pseudospectral time-domain (PSTD)
      algorithms are some of the most efficient time-domain numerical methods for
      engineering applications. One important drawback of these methods is the so
      called Gibbs phenomenon. This error can be avoided by using absorbing boundary
      conditions (ABC) at the end of the simulations. However, there is an important
      lack of ABC using a PSTD methods on a wave equation. In this paper, we present an
      ABC model based on a PSTD damped wave equation with an absorption parameter that
      depends on the position. Some examples of optimum variation profiles are studied
      analytically and numerically. Finally, the results of this model are also
      compared to another ABC model based on an hybrid formulation of the scalar
      perfectly matched layer. 

PMID- 24737967
TI  - Soft approximations and uni-int decision making.
AB  - Notions of core, support, and inversion of a soft set have been defined and
      studied. Soft approximations are soft sets developed through core and support and
      are used for granulating the soft space. Membership structure of a soft set has
      been probed in and many interesting properties are presented. We present a new
      conjecture to solve an optimum choice problem. Our Example 31 presents a case
      where the new conjecture solves the problem correctly. 

PMID- 24737968
TI  - An iterated tabu search approach for the clique partitioning problem.
AB  - Given an edge-weighted undirected graph with weights specifying dissimilarities
      between pairs of objects, represented by the vertices of the graph, the clique
      partitioning problem (CPP) is to partition the vertex set of the graph into
      mutually disjoint subsets such that the sum of the edge weights over all cliques
      induced by the subsets is as small as possible. We develop an iterated tabu
      search (ITS) algorithm for solving this problem. The proposed algorithm
      incorporates tabu search, local search, and solution perturbation procedures. We
      report computational results on CPP instances of size up to 2000 vertices.
      Performance comparisons of ITS against state-of-the-art methods from the
      literature demonstrate the competitiveness of our approach. 

PMID- 24737969
TI  - In vitro sustained release study of gallic acid coated with magnetite-PEG and
      magnetite-PVA for drug delivery system.
AB  - The efficacy of two nanocarriers polyethylene glycol and polyvinyl alcohol
      magnetic nanoparticles coated with gallic acid (GA) was accomplished via X-ray
      diffraction, infrared spectroscopy, magnetic measurements, thermal analysis, and
      TEM. X-ray diffraction and TEM results showed that Fe3O4 nanoparticles were pure
      iron oxide having spherical shape with the average diameter of 9 nm, compared
      with 31 nm and 35 nm after coating with polyethylene glycol-GA (FPEGG) and
      polyvinyl alcohol-GA (FPVAG), respectively. Thermogravimetric analyses proved
      that after coating the thermal stability was markedly enhanced. Magnetic
      measurements and Fourier transform infrared (FTIR) revealed that
      superparamagnetic iron oxide nanoparticles could be successfully coated with two
      polymers (PEG and PVA) and gallic acid as an active drug. Release behavior of
      gallic acid from two nanocomposites showed that FPEGG and FPVAG nanocomposites
      were found to be sustained and governed by pseudo-second-order kinetics.
      Anticancer activity of the two nanocomposites shows that the FPEGG demonstrated
      higher anticancer effect on the breast cancer cell lines in almost all
      concentrations tested compared to FPVAG.

PMID- 24737971
TI  - Morphological characteristics of renal artery and kidney in rats.
AB  - The gross anatomy and morphometry of the kidney and renal arteries were studied
      in the strains of laboratory rat: Sprague-Dawley (Sp) and Wistar (W) rats. Total
      of 106 three-dimensional endocasts of the intrarenal arteries of kidney that were
      prepared using standard injection-corrosion techniques were examined. A single
      renal artery was observed in 100% of the cases. The renal arteries were divided
      into a dorsal and a ventral branch. The dorsal and ventral branches were divided
      into two branches, the cranial and caudal branch. Renal arteries were classified
      into types I and II, depending on the cranial and caudal branches and their made
      of branching. The present study also showed that the right kidney was slightly
      heavier than the left one and that the kidney of the male was generally larger
      than that of the female. The mean live weights of the Sprague-Dawley and Wistar
      rats were found to be 258.26 +/- 5.9 and 182.4 +/- 19.05 g, respectively. The
      kidney weights were significantly correlated (P < 0.01) with body weights. The
      kidney weights were not found significantly correlated (P > 0.01) with the length
      of renal arteries.

PMID- 24737970
TI  - Parasitological and molecular observations on a little family outbreak of human
      fasciolosis diagnosed in Italy.
AB  - In the year 2010, three children who were born in a Romanian cattle farmer family
      went to Italy to join their mother. One of them was admitted to an Italian
      pediatric hospital for severe anemia that, when she was in her country, had been
      treated with blood transfusion. Blood tests and an abdominal ultrasound study
      triggered the suspicion of biliary parasitosis. The child underwent a
      cholangiopancreatography that caused the release of parasitic material
      microscopically identified as Fasciola hepatica. All children and their mother
      were submitted to coproparasitological analyses, which identified F. hepatica
      eggs only in the patient and in her twin sister. Parasitic materials recovered
      and flatworm specimens by us ad hoc obtained from Italian and Romanian cattle
      were genetically (ITS and COI genes) analyzed, and their sequences were compared
      with those deposited in GenBank. Specimens from children clustered with the
      Romanian strain examined and showed remarkable genetic differences with flatworm
      specimens from Italy. Anamnesis, parasite biology, and genetic data strongly
      suggest that twin sisters became infected in Romania; however, human fasciolosis
      is an emerging sanitary problem, favored by climate changes and global drivers;
      therefore, it deserves more attention on behalf of physicians working in both
      developing and developed countries. 

PMID- 24737972
TI  - A procedure to construct exact solutions of nonlinear fractional differential
      equations.
AB  - We use the fractional transformation to convert the nonlinear partial fractional
      differential equations with the nonlinear ordinary differential equations. The
      Exp-function method is extended to solve fractional partial differential
      equations in the sense of the modified Riemann-Liouville derivative. We apply the
      Exp-function method to the time fractional Sharma-Tasso-Olver equation, the space
      fractional Burgers equation, and the time fractional fmKdV equation. As a result,
      we obtain some new exact solutions. 

PMID- 24737973
TI  - Effect of multipath laser shock processing on microhardness, surface roughness,
      and wear resistance of 2024-T3 Al alloy.
AB  - Laser shock processing (LSP) is an innovative surface treatment technique with
      high peak power, short pulse, and cold hardening for strengthening metal
      materials. LSP is based on the application of a high intensity pulsed laser beam
      (I > 1 GW/cm(2); t < 50 ns) at the interface between the metallic target and the
      surrounding medium (a transparent confining material, normally water) forcing a
      sudden vaporization of the metallic surface into a high temperature and density
      plasma that immediately develops inducing a shock wave propagating into the
      material. The shock wave induces plastic deformation and a residual stress
      distribution in the target material. In this paper we study the increase of
      microhardness and surface roughness with the increase of laser pulse energy in
      2024-T3 Al alloy. The influence of the thickness of the confining layer (water)
      on microhardness and surface roughness is also studied. In addition, the effect
      of LSP treatment with best conditions on wear behaviors of the alloy was
      investigated.

PMID- 24737974
TI  - Expansive soil crack depth under cumulative damage.
AB  - The crack developing depth is a key problem to slope stability of the expansive
      soil and its project governance and the crack appears under the roles of dry-wet
      cycle and gradually develops. It is believed from the analysis that, because of
      its own cohesion, the expansive soil will have a certain amount of deformation
      under pulling stress but without cracks. The soil body will crack only when the
      deformation exceeds the ultimate tensile strain that causes cracks. And it is
      also believed that, due to the combined effect of various environmental factors,
      particularly changes of the internal water content, the inherent basic physical
      properties of expansive soil are weakened, and irreversible cumulative damages
      are eventually formed, resulting in the development of expansive soil cracks in
      depth. Starting from the perspective of volumetric strain that is caused by water
      loss, considering the influences of water loss rate and dry-wet cycle on crack
      developing depth, the crack developing depth calculation model which considers
      the water loss rate and the cumulative damages is established. Both the proposal
      of water loss rate and the application of cumulative damage theory to the
      expansive soil crack development problems try to avoid difficulties in matrix
      suction measurement, which will surely play a good role in promoting and
      improving the research of unsaturated expansive soil. 

PMID- 24737976
TI  - Vascular closure devices after endovascular procedures in swine: a reliable
      method?
AB  - PURPOSE: To investigate the safety and feasibility of the use of a vascular
      closure device (VCD) after endovascular procedures in swine. MATERIAL AND
      METHODS: In a study on endovascular therapy, VCD (StarClose, Abbott Vascular, Il,
      USA) was used in 20 female swines to achieve immediate hemostasis after
      percutaneous right femoral artery (FA) access. 10 animals were sacrificed
      immediately after the study and 10 animals were sacrificed 28 days after the
      initial study. To ensure complete hemostasis and patency of the femoral artery, a
      CT-angiography of the puncture site was performed on day 1 (acute and chronic
      group) and day 28 (chronic group). After the sacrifice, the femoral artery was
      explanted and examined macroscopically for signs of VCD dysfunction. RESULTS:
      Technical success rate was 100% with immediate hemostasis being achieved in all
      animals. No animals showed evidence of hematoma. During explantation, only small
      traces of coagulated blood were found in the acute group, while there were no
      signs of hematoma in the chronic group. CT-angiography immediately after VCD
      application as well as before sacrifice (chronic group) showed patency of the FA
      in all cases. CONCLUSION: The use of VCD to achieve hemostasis after endovascular
      studies in swine is feasible and safe.

PMID- 24737975
TI  - Percutaneous compression plate versus dynamic hip screw for treatment of
      intertrochanteric Hip fractures: a meta-analyse of five randomized controlled
      trials.
AB  - BACKGROUND: Percutaneous compression plating (PCCP) has been advocated to reduce
      blood loss, relieve pain, and lead to faster rehabilitation for the treatment of
      intertrochanteric fractures. The purpose of this meta-analysis was to estimate
      the outcomes and complications of the PCCP versus dynamic hip screw (DHS)
      fixation for intertrochanteric fractures. METHODS: All randomized controlled
      trials (RCT) that compared PCCP with DHS in treating adult patients with
      intertrochanteric fractures were included. Main outcomes were collected and
      analysed using the RevMan 5.1 version. RESULTS: Five trials met the inclusion
      criteria. Compared with DHS, PCCP had similar operation time (95% CI: 
      26.01~4.05, P = 0.15), length of hospitalization (95% CI: -1.79~1.25, P = 0.73),
      mortality (95% CI: 0.37~1.02, P = 0.06), incidence of implant-related
      complications (95% CI: 0.29~1.82, P = 0.49), and reoperation rate (95% CI:
      0.41~3.05, P = 0.83). But blood loss (95% CI: -173.84~-4.81, P = 0.04) and
      transfusion need (95% CI: -0.53~-0.07, P = 0.01) significantly favored the PCCP.
      CONCLUSIONS: The PCCP was associated with reduced blood loss and less transfusion
      need, but similar to DHS in other respects. Owing to the limitations of this
      systematic review, more high-quality RCTs are still needed to assess the clinical
      efficiency of PCCP.

PMID- 24737977
TI  - Minimal solution of singular LR fuzzy linear systems.
AB  - In this paper, the singular LR fuzzy linear system is introduced. Such systems
      are divided into two parts: singular consistent LR fuzzy linear systems and
      singular inconsistent LR fuzzy linear systems. The capability of the generalized
      inverses such as Drazin inverse, pseudoinverse, and {1}-inverse in finding
      minimal solution of singular consistent LR fuzzy linear systems is investigated. 

PMID- 24737978
TI  - Processing uncertain RFID data in traceability supply chains.
AB  - Radio Frequency Identification (RFID) is widely used to track and trace objects
      in traceability supply chains. However, massive uncertain data produced by RFID
      readers are not effective and efficient to be used in RFID application systems.
      Following the analysis of key features of RFID objects, this paper proposes a new
      framework for effectively and efficiently processing uncertain RFID data, and
      supporting a variety of queries for tracking and tracing RFID objects. We adjust
      different smoothing windows according to different rates of uncertain data,
      employ different strategies to process uncertain readings, and distinguish ghost,
      missing, and incomplete data according to their apparent positions. We propose a
      comprehensive data model which is suitable for different application scenarios.
      In addition, a path coding scheme is proposed to significantly compress massive
      data by aggregating the path sequence, the position, and the time intervals. The
      scheme is suitable for cyclic or long paths. Moreover, we further propose a
      processing algorithm for group and independent objects. Experimental evaluations
      show that our approach is effective and efficient in terms of the compression and
      traceability queries. 

PMID- 24737980
TI  - Performance analysis of relay subset selection for amplify-and-forward cognitive
      relay networks.
AB  - Cooperative communication is regarded as a key technology in wireless networks,
      including cognitive radio networks (CRNs), which increases the diversity order of
      the signal to combat the unfavorable effects of the fading channels, by allowing
      distributed terminals to collaborate through sophisticated signal processing.
      Underlay CRNs have strict interference constraints towards the secondary users
      (SUs) active in the frequency band of the primary users (PUs), which limits their
      transmit power and their coverage area. Relay selection offers a potential
      solution to the challenges faced by underlay networks, by selecting either single
      best relay or a subset of potential relay set under different design requirements
      and assumptions. The best relay selection schemes proposed in the literature for
      amplify-and-forward (AF) based underlay cognitive relay networks have been very
      well studied in terms of outage probability (OP) and bit error rate (BER), which
      is deficient in multiple relay selection schemes. The novelty of this work is to
      study the outage behavior of multiple relay selection in the underlay CRN and
      derive the closed-form expressions for the OP and BER through cumulative
      distribution function (CDF) of the SNR received at the destination. The
      effectiveness of relay subset selection is shown through simulation results. 

PMID- 24737979
TI  - A Schiff base-derived copper (II) complex is a potent inducer of apoptosis in
      colon cancer cells by activating the intrinsic pathway.
AB  - Metal-based drugs with extensive clinical applications hold great promise for the
      development of cancer chemotherapeutic agents. In the last few decades, Schiff
      bases and their complexes have become well known for their extensive biological
      potential. In the present study, we examined the antiproliferative effect of a
      copper (II) complex on HT-29 colon cancer cells. The Cu(BrHAP)2 Schiff base
      compound demonstrated a potent antiproliferative effect in HT-29 cells, with an
      IC50 value of 2.87  MUg/ml after 72 h of treatment. HT-29 cells treated with Cu
      (II) complexes underwent apoptosis death, as exhibited by a progressive elevation
      in the proportion of the G1 cell population. At a concentration of 6.25  MUg/ml,
      the Cu(BrHAP)2 compound caused significant elevation in ROS production following
      perturbation of mitochondrial membrane potential and cytochrome c release, as
      assessed by the measurement of fluorescence intensity in stained cells.
      Furthermore, the activation of caspases 3/7 and 9 was part of the Cu (II) complex
      induced apoptosis, which confirmed the involvement of mitochondrial-mediated
      apoptosis. Meanwhile, there was no significant activation of caspase-8. Taken
      together, these results imply that the Cu(BrHAP)2 compound is a potential
      candidate for further in vivo and clinical colon cancer studies to develop novel
      chemotherapeutic agents derived from metal-based agents.

PMID- 24737981
TI  - Investigation on mercury reemission from limestone-gypsum wet flue gas
      desulfurization slurry.
AB  - Secondary atmospheric pollutions may result from wet flue gas desulfurization
      (WFGD) systems caused by the reduction of Hg(2+) to Hg(0) and lead to a damping
      of the cobenefit mercury removal efficiency by WFGD systems. The experiment on
      Hg(0) reemission from limestone-gypsum WFGD slurry was carried out by changing
      the operating conditions such as the pH, temperature, Cl(-) concentrations, and
      oxygen concentrations. The partitioning behavior of mercury in the solid and
      liquid byproducts was also discussed. The experimental results indicated that the
      Hg(0) reemission rate from WFGD slurry increased as the operational temperatures
      and pH values increased. The Hg(0) reemission rates decreased as the O2
      concentration of flue gas and Cl(-) concentration of WFGD slurry increased. The
      concentrations of O2 in flue gas have an evident effect on the mercury retention
      in the solid byproducts. The temperature and Cl(-) concentration have a slight
      effect on the mercury partitioning in the byproducts. No evident relation was
      found between mercury retention in the solid byproducts and the pH. The present
      findings could be valuable for industrial application of characterizing and
      optimizing mercury control in wet FGD systems. 

PMID- 24737982
TI  - Combining ability of pod yield and related traits of groundnut (Arachis hypogaea
      L.) under salinity stress.
AB  - A study was performed using 6 * 6 F1 diallel population without reciprocals to
      assess the mode of inheritance of pod yield and related traits in groundnut with
      imposed salinity stress. Heterosis was found for pod number and yield. Data on
      general and specific combining ability (gca and sca) indicated additive and
      nonadditive gene actions. The gca: sca ratios were much less than unity
      suggesting predominant role of nonadditive gene effects. Cultivars
      "Binachinabadam-2" and "Dacca-1" and mutant M6/25/64-82 had the highest, second
      highest, and third highest pod number, as well as gca values, respectively. These
      two cultivars and another mutant M6/15/70-19 also had the highest, second
      highest, and third highest pod yield, as well as gca values, respectively.
      Therefore, "Dacca-1", "Binachinabadam-2", M6/25/64-82, and M6/15/70-19 could be
      used as source of salinity tolerance. Cross combinations showing high sca effects
      arising from parents with high and low gca values for any trait indicate the
      influence of nonadditive genes on their expression. Parents of these crosses can
      be used for biparental mating or reciprocal recurrent selection for developing
      high yielding varieties. Crosses with high sca effects having both parents with
      good gca effects could be exploited by pedigree breeding to get transgressive
      segregants. 

PMID- 24737983
TI  - Homotopic approximate solutions for the perturbed CKdV equation with variable
      coefficients.
AB  - This work concerns how to find the double periodic form of approximate solutions
      of the perturbed combined KdV (CKdV) equation with variable coefficients by using
      the homotopic mapping method. The obtained solutions may degenerate into the
      approximate solutions of hyperbolic function form and the approximate solutions
      of trigonometric function form in the limit cases. Moreover, the first order
      approximate solutions and the second order approximate solutions of the variable
      coefficients CKdV equation in perturbation epsilonu (n) are also induced. 

PMID- 24737984
TI  - A lightweight neighbor-info-based routing protocol for no-base-station taxi-call
      system.
AB  - Since the quick topology change and short connection duration, the VANET has had
      unstable routing and wireless signal quality. This paper proposes a kind of
      lightweight routing protocol-LNIB for call system without base station, which is
      applicable to the urban taxis. LNIB maintains and predicts neighbor information
      dynamically, thus finding the reliable path between the source and the target.
      This paper describes the protocol in detail and evaluates the performance of this
      protocol by simulating under different nodes density and speed. The result of
      evaluation shows that the performance of LNIB is better than AODV which is a
      classic protocol in taxi-call scene. 

PMID- 24737985
TI  - Removal dynamics of nitric oxide (NO) pollutant gas by pulse-discharged plasma
      technique.
AB  - Nonthermal plasma technique has drawn extensive attentions for removal of air
      pollutants such as NO x and SO2. The NO removal mechanism in pulse discharged
      plasma is discussed in this paper. Emission spectra diagnosis indicates that the
      higher the discharge voltage is, the more the NO are removed and transformed into
      O, N, N2, NO2, and so forth. Plasma electron temperature T(e) is ranged from 6400
      K at 2.4 kV discharge voltage to 9500 K at 4.8 kV. After establishing a zero
      dimensional chemical reaction kinetic model, the major reaction paths are
      clarified as the electron collision dissociation of NO into N and O during
      discharge and followed by single substitution of N on NO to form N2 during and
      after discharge, compared with the small fraction of NO2 formed by oxidizing NO.
      The reaction directions can be adjusted by N2 additive, and the optimal N2/NO
      mixing ratio is 2 : 1. Such a ratio not only compensates the disadvantage of
      electron competitive consumption by the mixed N2, but also heightens the total NO
      removal extent through accelerating the NO oxidization process.

PMID- 24737986
TI  - 3D online submicron scale observation of mixed metal powder's microstructure
      evolution in high temperature and microwave compound fields.
AB  - In order to study the influence on the mechanical properties caused by
      microstructure evolution of metal powder in extreme environment, 3D real-time
      observation of the microstructure evolution of Al-Ti mixed powder in high
      temperature and microwave compound fields was realized by using synchrotron
      radiation computerized topography (SR-CT) technique; the spatial resolution was
      enhanced to 0.37  MUm/pixel through the designed equipment and the introduction
      of excellent reconstruction method for the first time. The process of
      microstructure evolution during sintering was clearly distinguished from 2D and
      3D reconstructed images. Typical sintering parameters such as sintering neck
      size, porosity, and particle size of the sample were presented for quantitative
      analysis of the influence on the mechanical properties and the sintering kinetics
      during microwave sintering. The neck size-time curve was obtained and the neck
      growth exponent was 7.3, which indicated that surface diffusion was the main
      diffusion mechanism; the reason was the eddy current loss induced by the external
      microwave fields providing an additional driving force for mass diffusion on the
      particle surface. From the reconstructed images and the curve of porosity and
      average particle size versus temperature, it was believed that the presence of
      liquid phase aluminum accelerated the densification and particle growth.

PMID- 24737987
TI  - Brain embolism secondary to cardiac myxoma in fifteen Chinese patients.
AB  - BACKGROUND: Heart myxoma-related embolisms commonly involve the central nervous
      system, but data are lacking in Chinese patients. METHODS: 27 patients diagnosed
      with myxoma were reviewed retrospectively. RESULTS: Among 27 patients, fourteen
      (51.9%) patients were women. Fifteen (55.6%) patients had brain embolisms.
      Rarely, patients were misdiagnosed with central nervous system vasculitis (n =
      2), moyamoya disease (n = 1), and neuromyelitis optica (n = 1). We found positive
      associations between mRS (>3) and female gender (r = 0.873, P < 0.0001),
      infection (r = 0.722, P = 0.002), severe complications (r = 0.722, P = 0.002),
      systolic blood pressure (SBP) of <120 mmHg (r = 0.6, P = 0.018), WBC count of >10
      * 10(9)/L (r = 0.722, P = 0.002), tumour size (r = 0.866, P < 0.0001), bilateral
      brain lesions (r = 0.60, P = 0.018), and total anterior circulation infarction
      (TACI) (r = 0.667, P = 0.007). The independent relationships among these factors
      and outcomes could not be confirmed (P > 0.05). CONCLUSIONS: Neurologic
      manifestations in Chinese patients with cardiac myxoma-related stroke were
      complicated and multifarious. Female gender, infection, other severe
      complications, low SBP, tumour size, bilateral brain lesions, TACI, and high WBC
      counts could be associated with a poor prognosis.

PMID- 24737989
TI  - A new type fuzzy module over fuzzy rings.
AB  - A new kind of fuzzy module over a fuzzy ring is introduced by generalizing Yuan
      and Lee's definition of the fuzzy group and Aktas and Cagman's definition of
      fuzzy ring. The concepts of fuzzy submodule, and fuzzy module homomorphism are
      studied and some of their basic properties are presented analogous of ordinary
      module theory. 

PMID- 24737988
TI  - Extracts of Artocarpus communis decrease alpha-melanocyte stimulating hormone
      induced melanogenesis through activation of ERK and JNK signaling pathways.
AB  - Artocarpus communis is an agricultural plant that is also used in folk medicine
      to prevent skin diseases, including acne and dermatitis. Extracts of A. communis
      have been used to effectively inhibit melanogenesis; however, the
      antimelanogenesis mechanism of these extracts has not yet been investigated. The
      present study utilized a cell-free tyrosinase assay as well as alpha-melanocyte
      stimulating hormone- (-MSH-) induced tyrosinase assay conducted in B16F10 cells,
      performed a cytotoxicity assay, and determined cellular melanin content to
      examine the effects of a methanolic extract of A. communis (ACM) and various
      organic partition fractions of A. communis on melanogenesis. In addition, we
      performed western blot analysis to elucidate the mechanism of their
      antimelanogenesis effect. Our results indicated that, except for the n-hexane
      extract, ACM and the various partition extracts at noncytotoxic concentrations
      effectively decreased melanin content and tyrosinase activity by downregulating
      microphthalmia-associated transcription factor (MITF) and phosphorylated cAMP
      response element-binding protein (p-CREB). Moreover, ACM and the partition
      fractions activated phosphorylation of extracellular signal-regulated kinase
      (ERK) and c-Jun N-terminal kinase (JNK) to inhibit the synthesis of MITF and
      finally to decrease melanin production. In conclusion, we suggest that
      noncytotoxic concentrations of ACM and the various partition fractions may be
      useful as references for developing skin-lighting agents for use in medicines or
      cosmetics.

PMID- 24737990
TI  - In vivo healing potential of Aegle marmelos in excision, incision, and dead space
      wound models.
AB  - The study incorporates the wound healing potential of Aegle marmelos fruit pulp
      extract (AME) on excision, incision, and dead space wound models in rats. AME
      (200 mg/kg) was administered orally once daily for variable days depending on the
      type of wound ulcer study. AME was studied for its wound breaking strength
      (incision wound), rate of contraction, period of epithelization and histology of
      skin (excision model), and granulation tissue free radicals, antioxidants, acute
      inflammatory marker, and connective tissue markers and deep connective tissue
      histology (dead space wound). Complete wound contraction and epithelization were
      observed at the 20th day after treatment with AME as compared to the 24th day in
      control rats. Mean epithelization period and scar area were decreased while wound
      breaking strength was increased with AME compared with control. Granulation
      tissue showed increased levels of collagen determinants (33.7 to 64.4%, P <
      0.001) and antioxidants (13.0 to 38.8%, P < 0.05 to P < 0.001), whereas markers
      of oxidative stress (55.0 to 55.6%, P < 0.001) and myeloperoxidase (21.3%, P <
      0.001) were decreased in AME treated group. A. marmelos seems to promote wound
      healing by enhancing connective tissue formation and antioxidants status with
      decrease in free radicals and myeloperoxidase having tissue damaging effects.

PMID- 24737992
TI  - Comparative performance of four single extreme outlier discordancy tests from
      Monte Carlo simulations.
AB  - Using highly precise and accurate Monte Carlo simulations of 20,000,000
      replications and 102 independent simulation experiments with extremely low
      simulation errors and total uncertainties, we evaluated the performance of four
      single outlier discordancy tests (Grubbs test N2, Dixon test N8, skewness test
      N14, and kurtosis test N15) for normal samples of sizes 5 to 20. Statistical
      contaminations of a single observation resulting from parameters called delta
      from +/-0.1 up to +/-20 for modeling the slippage of central tendency or epsilon
      from +/-1.1 up to +/-200 for slippage of dispersion, as well as no contamination
      (delta = 0 and epsilon = +/-1), were simulated. Because of the use of precise and
      accurate random and normally distributed simulated data, very large replications,
      and a large number of independent experiments, this paper presents a novel
      approach for precise and accurate estimations of power functions of four popular
      discordancy tests and, therefore, should not be considered as a simple simulation
      exercise unrelated to probability and statistics. From both criteria of the Power
      of Test proposed by Hayes and Kinsella and the Test Performance Criterion of
      Barnett and Lewis, Dixon test N8 performs less well than the other three tests.
      The overall performance of these four tests could be summarized as N2?N15 > N14 >
      N8. 

PMID- 24737991
TI  - Expression patterns of ERF genes underlying abiotic stresses in di-haploid
      Populus simonii * P. nigra.
AB  - 176 ERF genes from Populus were identified by bioinformatics analysis, 13 of
      these in di-haploid Populus simonii * P. nigra were investigate by real-time RT
      PCR, the results demonstrated that 13 ERF genes were highly responsive to salt
      stress, drought stress and ABA treatment, and all were expressed in root, stem,
      and leaf tissues, whereas their expression levels were markedly different in the
      various tissues. In roots, PthERF99, 110, 119, and 168 were primarily
      downregulated under drought and ABA treatment but were specifically upregulated
      under high salt condition. Interestingly, in poplar stems, all ERF genes showed
      the similar trends in expression in response to NaCl stress, drought stress, and
      ABA treatment, indicating that they may not play either specific or unique roles
      in stems in abiotic stress responses. In poplar leaves, PthERF168 was highly
      induced by ABA treatment, but was suppressed by high salinity and drought
      stresses, implying that PthERF168 participated in the ABA signaling pathway. The
      results of this study indicated that ERF genes could play essential but distinct
      roles in various plant tissues in response to different environment cues and
      hormonal treatment. 

PMID- 24737993
TI  - Response of a hypersonic boundary layer to freestream pulse acoustic disturbance.
AB  - The response of hypersonic boundary layer over a blunt wedge to freestream pulse
      acoustic disturbance was investigated. The stability characteristics of boundary
      layer for freestream pulse wave and continuous wave were analyzed comparatively.
      Results show that freestream pulse disturbance changes the thermal conductivity
      characteristics of boundary layer. For pulse wave, the number of main disturbance
      clusters decreases and the frequency band narrows along streamwise. There are
      competition and disturbance energy transfer among different modes in boundary
      layer. The dominant mode of boundary layer has an inhibitory action on other
      modes. Under continuous wave, the disturbance modes are mainly distributed near
      fundamental and harmonic frequencies, while under pulse wave, the disturbance
      modes are widely distributed in different modes. For both pulse and continuous
      waves, most of disturbance modes slide into a lower-growth or decay state in
      downstream, which is tending towards stability. The amplitude of disturbance
      modes in boundary layer under continuous wave is considerably larger than pulse
      wave. The growth rate for the former is also considerably larger than the later
      the disturbance modes with higher growth are mainly distributed near fundamental
      and harmonic frequencies for the former, while the disturbance modes are widely
      distributed in different frequencies for the latter. 

PMID- 24737994
TI  - Multivariate analysis, mass balance techniques, and statistical tests as tools in
      igneous petrology: application to the Sierra de las Cruces volcanic range
      (Mexican Volcanic Belt).
AB  - Magmatic processes have usually been identified and evaluated using qualitative
      or semiquantitative geochemical or isotopic tools based on a restricted number of
      variables. However, a more complete and quantitative view could be reached
      applying multivariate analysis, mass balance techniques, and statistical tests.
      As an example, in this work a statistical and quantitative scheme is applied to
      analyze the geochemical features for the Sierra de las Cruces (SC) volcanic range
      (Mexican Volcanic Belt). In this locality, the volcanic activity (3.7 to 0.5 Ma)
      was dominantly dacitic, but the presence of spheroidal andesitic enclaves and/or
      diverse disequilibrium features in majority of lavas confirms the operation of
      magma mixing/mingling. New discriminant-function-based multidimensional diagrams
      were used to discriminate tectonic setting. Statistical tests of discordancy and
      significance were applied to evaluate the influence of the subducting Cocos
      plate, which seems to be rather negligible for the SC magmas in relation to
      several major and trace elements. A cluster analysis following Ward's linkage
      rule was carried out to classify the SC volcanic rocks geochemical groups.
      Finally, two mass-balance schemes were applied for the quantitative evaluation of
      the proportion of the end-member components (dacitic and andesitic magmas) in the
      comingled lavas (binary mixtures).

PMID- 24737995
TI  - Chronic kidney disease stage is a modulator on the association between high
      sensitivity C-reactive protein and coronary vasospastic angina.
AB  - The prevalence of coronary vasospasm and also the factors associated with
      coronary vasospasm in CKD is still unclear. In this cross-sectional study of 859
      consecutive CKD patients with angina pectoris received coronary catheterization,
      we evaluated the factors associated with coronary vasospasm. Patients with
      vasospasm were older and had higher peripheral blood white cell counts, higher
      peripheral blood monocyte cell counts, higher haemoglobin levels, higher hs-CRP
      levels, and lower levels of serum creatinine than patients without vasospasm. The
      results of multivariate logistic regression analysis revealed that peripheral
      blood monocyte count and hs-CRP level were independently associated with coronary
      vasospasm in patients with stage 1 CKD. Only peripheral blood monocyte count but
      not hs-CRP was independently associated with coronary vasospasm in patients with
      stages 2 and 3 of CKD. In conclusion, peripheral blood monocyte count is
      independently associated with coronary vasospasm in patients with stage 1-3 CKD,
      whereas hs-CRP is only independently associated with coronary vasospasm in
      patients with stage 1 CKD. 

PMID- 24737996
TI  - MWAHCA: a multimedia wireless ad hoc cluster architecture.
AB  - Wireless Ad hoc networks provide a flexible and adaptable infrastructure to
      transport data over a great variety of environments. Recently, real-time audio
      and video data transmission has been increased due to the appearance of many
      multimedia applications. One of the major challenges is to ensure the quality of
      multimedia streams when they have passed through a wireless ad hoc network. It
      requires adapting the network architecture to the multimedia QoS requirements. In
      this paper we propose a new architecture to organize and manage cluster-based ad
      hoc networks in order to provide multimedia streams. Proposed architecture adapts
      the network wireless topology in order to improve the quality of audio and video
      transmissions. In order to achieve this goal, the architecture uses some
      information such as each node's capacity and the QoS parameters (bandwidth,
      delay, jitter, and packet loss). The architecture splits the network into
      clusters which are specialized in specific multimedia traffic. The real system
      performance study provided at the end of the paper will demonstrate the
      feasibility of the proposal. 

PMID- 24737997
TI  - Multiview discriminative geometry preserving projection for image classification.
AB  - In many image classification applications, it is common to extract multiple
      visual features from different views to describe an image. Since different visual
      features have their own specific statistical properties and discriminative powers
      for image classification, the conventional solution for multiple view data is to
      concatenate these feature vectors as a new feature vector. However, this simple
      concatenation strategy not only ignores the complementary nature of different
      views, but also ends up with "curse of dimensionality." To address this problem,
      we propose a novel multiview subspace learning algorithm in this paper, named
      multiview discriminative geometry preserving projection (MDGPP) for feature
      extraction and classification. MDGPP can not only preserve the intraclass
      geometry and interclass discrimination information under a single view, but also
      explore the complementary property of different views to obtain a low-dimensional
      optimal consensus embedding by using an alternating-optimization-based iterative
      algorithm. Experimental results on face recognition and facial expression
      recognition demonstrate the effectiveness of the proposed algorithm. 

PMID- 24737998
TI  - Granular computing classification algorithms based on distance measures between
      granules from the view of set.
AB  - Granular computing classification algorithms are proposed based on distance
      measures between two granules from the view of set. Firstly, granules are
      represented as the forms of hyperdiamond, hypersphere, hypercube, and hyperbox.
      Secondly, the distance measure between two granules is defined from the view of
      set, and the union operator between two granules is formed to obtain the granule
      set including the granules with different granularity. Thirdly the threshold of
      granularity determines the union between two granules and is used to form the
      granular computing classification algorithms based on distance measures (DGrC).
      The benchmark datasets in UCI Machine Learning Repository are used to verify the
      performance of DGrC, and experimental results show that DGrC improved the testing
      accuracies. 

PMID- 24737999
TI  - Identification of psychological dysfunctions and eating disorders in obese women
      seeking weight loss: cross-sectional study.
AB  - Objective. The aim of this study is to analyse associations between eating
      behaviour and psychological dysfunctions in treatment-seeking obese patients and
      identify parameters for the development of diagnostic tools with regard to eating
      and psychological disorders. Design and Methods. Cross-sectional data were
      analysed from 138 obese women. Bulimic Investigatory Test of Edinburgh and Eating
      Disorder Inventory-2 assessed eating behaviours. Beck Depression Inventory II,
      Spielberger State-Trait Anxiety Inventory, form Y, Rathus Assertiveness Schedule,
      and Marks and Mathews Fear Questionnaire assessed psychological profile. Results.
      61% of patients showed moderate or major depressive symptoms and 77% showed
      symptoms of anxiety. Half of the participants presented with a low degree of
      assertiveness. No correlation was found between psychological profile and age or
      anthropometric measurements. The prevalence and severity of depression, anxiety,
      and assertiveness increased with the degree of eating disorders. The feeling of
      ineffectiveness explained a large degree of score variance. It explained 30 to
      50% of the variability of assertiveness, phobias, anxiety, and depression.
      Conclusion. Psychological dysfunctions had a high prevalence and their severity
      is correlated with degree of eating disorders. The feeling of ineffectiveness
      constitutes the major predictor of the psychological profile and could open new
      ways to develop screening tools. 

PMID- 24738000
TI  - Effects of long-term testosterone therapy on patients with "diabesity": results
      of observational studies of pooled analyses in obese hypogonadal men with type 2
      diabetes.
AB  - To investigate effects of long-term testosterone (T) therapy in obese men with T
      deficiency (TD) and type 2 diabetes mellitus (T2DM), data were collected from two
      observational, prospective, and cumulative registry studies of 561 men with TD
      receiving T therapy for up to 6 years. A subgroup of obese hypogonadal men with
      T2DM was analyzed. Weight, height, waist circumference (WC), fasting blood
      glucose (FBG), glycated haemoglobin (HbA1c) blood pressure, lipid profile, C
      reactive protein (CRP), and liver enzymes were measured. A total of 156 obese,
      diabetic men with T deficiency, aged 61.17 +/- 6.18 years, fulfilled selection
      criteria. Subsequent to T therapy, WC decreased by 11.56 cm and weight declined
      by 17.49 kg (15.04%). Fasting glucose declined from 7.06 +/- 1.74 to 5.59 +/-
      0.94 mmol/L (P < 0.0001 for all). HbA1c decreased from 8.08 to 6.14%, with a mean
      change of 1.93%. Systolic and diastolic blood pressure, lipid profiles including
      total cholesterol: HDL ratio, CRP, and liver enzymes all improved (P < 0.0001).
      Long-term T therapy for up to 6 years resulted in significant and sustained
      improvements in weight, T2DM, and other cardiometabolic risk factors in obese,
      diabetic men with TD and this therapy may play an important role in the
      management of obesity and diabetes (diabesity) in men with T deficiency. 

PMID- 24738001
TI  - Basal-Supported Oral Therapy with Sitagliptin Counteracts Rebound Hyperglycemia
      Caused by GLP-1 Tachyphylaxis.
AB  - Introduction. Treatment with a glucagon-like peptide 1 (GLP-1) analog fails in
      some patients due to rebound hyperglycemia caused by tachyphylaxis (GLP-1
      tachyphylaxis). We investigated the efficacy of basal-supported oral therapy
      (BOT) with insulin glargine and sitagliptin for counteracting GLP-1
      tachyphylaxis. Materials and Methods. The subjects were 12 men and 3 women aged
      59.9 +/- 10.0 years who had been treated with GLP-1 analogs. All of them had
      developed rebound hyperglycemia caused by GLP-1 tachyphylaxis. Their GLP-1 analog
      based therapy was switched to BOT with insulin glargine plus sitagliptin and
      other medications. The primary outcomes were whether switching of therapy was
      associated with a change of hemoglobin A1c (HbA1c) and whether weight gain
      occurred. Results. Baseline HbA1c was 8.0 +/- 0.9%. It decreased to 7.3 +/- 0.9%
      at 3 months after switching (P < 0.01) and to 7.2 +/- 0.9% at 4 months (P <
      0.05). Weight gain was 1.1 kg after 1 month (P < 0.01) and 2.3 kg after 5 months
      (P < 0.01). Conclusion. Switching to BOT with insulin glargine and sitagliptin
      improved glycemic control. The significant decrease of HbA1c demonstrated that
      this combination can counteract deterioration of glycemic control due to rebound
      hyperglycemia secondary to GLP-1 tachyphylaxis. However, weight gain remains a
      problem. 

PMID- 24738002
TI  - Mesenchymal stem cell biodistribution, migration, and homing in vivo.

PMID- 24738003
TI  - The active role of leguminous plant components in type 2 diabetes.
AB  - Diabetes appears to be one of the most frequent noncommunicable diseases in the
      world. A permanent growth in the incidence of diabetes can be observed and
      according to the International Diabetes Federation (IDF) the year 2030 will mark
      the increase in the number of diabetics to 439 mln worldwide. Type 2 diabetes
      accounts for about 90% of all diabetes incidence. Nutrition model modification
      not only features the basic element in type 2 diabetes treatment but also
      constitutes the fundamental factor influencing a morbidity rate decrease.
      Leguminous plants are a key factor in the diabetic diet; plants such as pulses or
      soybeans are nutritious products valued highly in nutrition. These legumes are
      high in the content of wholesome protein and contain large amounts of soluble
      alimentary fiber fractions, polyunsaturated fatty acids, vitamins and minerals,
      and bioactive substances with antioxidant, anti-inflammatory, and anticancer
      activity. They are distinguished by the high amount of bioactive compounds that
      may interfere with the metabolism of glucose. The most significant bioactive
      compounds displaying antidiabetic activity in leguminous plants are as follows:
      genistein and daidzein, alpha-amylase inhibitors, and alpha-glucosidase
      inhibitors. In vitro research using leguminous plant extracts has confirmed their
      antidiabetic properties. Leguminous plants should be employed in the promotion of
      healthy lifestyles in terms of functional food. 

PMID- 24738004
TI  - Cytomorphometric analysis of exfoliated cells in oral lichen planus.
AB  - BACKGROUND: Tumors are distinguished from normal tissues partly by their
      pronounced variability of cellular and nuclear dimensions. Therefore, such
      factors may be an indicator to assess whether the cells are malignant or not.
      Exfoliative cytology is a reliable tool in assessing such changes in the uterine
      cervix and has been used in the oral cavity also with success. The aims and
      objectives of the following study were to evaluate the malignant changes by
      assessing the quantitative parameters such as cytoplasmic diameter, cytoplasmic
      perimeter and cytoplasmic area (CD, CP, CA) and nuclear diameter, nuclear
      perimeter and nuclear area (ND, NP, NA) and cytoplasmic to nuclear ratio in the
      exfoliated cells of various subtypes of oral lichen planus (OLP) using
      cytomorphometry. MATERIALS AND METHODS: Oral exfoliated cells from nineteen cases
      of histologically proven OLP (1 atrophic, 13 reticular, 4 erosive and 1 plaque)
      and ten controls with healthy mucosa were taken and stained by Feulgen-Rossenback
      reaction and cytomorphometric analysis was performed using an image analysis
      software. The parameters taken into account were CD, CP, CA and ND, NP, NA.
      Furthermore CA/NA was calculated. The parameters were statistically analyzed
      using the t-test. RESULTS: Cytomorphometric analysis of all the parameters showed
      no significant difference between the control group and the reticular/plaque
      subtypes, whereas statistically significant (P < 0.05) differences was obtained
      between the control group and the atrophic/erosive subtypes group when compared
      using t-test. CONCLUSIONS: The cytomorphometric analysis of OLP shows that
      erosive/atrophic subtypes of OLP are at more risk and exfoliative cytology and
      cytomorphometry can be used as a tool to assess the malignant changes.

PMID- 24738005
TI  - Pleural fluid metastases of salivary duct carcinoma: A case report and review of
      the literature.
AB  - Salivary duct carcinoma (SDC) comprises a small proportion of salivary gland
      tumors; however, it is known to be aggressive with a high rate of metastasis.
      Although frequent references are made to pulmonary dissemination, metastases in
      the pleural fluid have not been described. In this article, we report the
      cytologic features of metastatic SDC in the pleural fluid. The clinical history,
      cytomorphology and immunohistochemical features used for diagnosis are described.
      To the best of our knowledge, this is the first case of pleural fluid involvement
      by salivary duct carcinoma reported in the literature. 

PMID- 24738006
TI  - Computational neuroscience.

PMID- 24738007
TI  - A new ratio for protocol categorization.
AB  - The present review describes and validates a new ratio "S" created for matching
      predictability and balance between TP and TN. Validity of S was studied in a
      three-step process as follows: (i) S was applied to the data of a past study
      predicting cardiac output response to fluid bolus from response to passive leg
      raise (PLR); (ii) S was comparatively analyzed with traditional ratios by
      modeling different 2 * 2 contingency tables in 1000 hypothetical patients; (iii)
      precision of S was compared with other ratios by computing random fluctuations in
      the same patients. In comparison to other ratios, S performs better in predicting
      the cardiac response to fluid bolus and supports more directly the clinical
      conclusions. When the proportion of false responses is high, S is close to the
      coefficient correlation (CC). When the proportion of true responses is high, S is
      the unique ratio that identifies the categorization that balances the proportion
      of TP and TN. The precision of S is close to that of CC. In conclusion, S should
      be considered for creating categories from quantitative variables; especially
      when matching predictability with balance between TP and TN is a concern. 

PMID- 24738008
TI  - Independent component analysis of instantaneous power-based fMRI.
AB  - In functional magnetic resonance imaging (fMRI) studies using spatial independent
      component analysis (sICA) method, a model of "latent variables" is often
      employed, which is based on the assumption that fMRI data are linear mixtures of
      statistically independent signals. However, actual fMRI signals are nonlinear and
      do not automatically meet with the requirement of sICA. To provide a better
      solution to this problem, we proposed a novel approach termed instantaneous power
      based fMRI (ip-fMRI) for regularization of fMRI data. Given that the
      instantaneous power of fMRI signals is a scalar value, it should be a linear
      mixture that naturally satisfies the "latent variables" model. Based on our
      simulated data, the curves of accuracy and resulting receiver-operating
      characteristic curves indicate that the proposed approach is superior to the
      traditional fMRI in terms of accuracy and specificity by using sICA. Experimental
      results from human subjects have shown that spatial components of a hand movement
      task-induced activation reveal a brain network more specific to motor function by
      ip-fMRI than that by the traditional fMRI. We conclude that ICA decomposition of
      ip-fMRI may be used to localize energy signal changes in the brain and may have a
      potential to be applied to detection of brain activity. 

PMID- 24738009
TI  - Mimicking pregnancy as a strategy for breast cancer prevention.
AB  - Pregnancy and its effects on breast cancer risk have been widely investigated;
      there is consensus among researchers that early pregnancy confers protection
      against breast cancer later in life, whereas nulliparity and late-age parity have
      been associated with increased risk of developing breast cancer. The answer to
      the question of how pregnancy reduces breast cancer risk has been elusive;
      however, pregnancy, like breast cancer, is a similar hormone-dependent entity
      under direct control of estrogen, progesterone and, of particular importance,
      human chorionic gonadotropin (hCG). In this report, we emphasize the main
      changes, previously described by our laboratory, in morphology and gene
      expression levels of the mammary gland of Sprague-Dawley rats exposed to known
      cancer-preventative conditions (pregnancy, hCG and progesterone + estrogen). In
      addition, we postulate a protective mechanism induced by hCG that could reduce
      the cell's potential to be transformed by carcinogens.

PMID- 24738010
TI  - Extensional flow of hyaluronic acid solutions in an optimized microfluidic cross
      slot device.
AB  - We utilize a recently developed microfluidic device, the Optimized Shape Cross
      slot Extensional Rheometer (OSCER), to study the elongational flow behavior and
      rheological properties of hyaluronic acid (HA) solutions representative of the
      synovial fluid (SF) found in the knee joint. The OSCER geometry is a stagnation
      point device that imposes a planar extensional flow with a homogenous extension
      rate over a significant length of the inlet and outlet channel axes. Due to the
      compressive nature of the flow generated along the inlet channels, and the planar
      elongational flow along the outlet channels, the flow field in the OSCER device
      can also be considered as representative of the flow field that arises between
      compressing articular cartilage layers of the knee joints during running or
      jumping movements. Full-field birefringence microscopy measurements demonstrate a
      high degree of localized macromolecular orientation along streamlines passing
      close to the stagnation point of the OSCER device, while micro-particle image
      velocimetry is used to quantify the flow kinematics. The stress-optical rule is
      used to assess the local extensional viscosity in the elongating fluid elements
      as a function of the measured deformation rate. The large limiting values of the
      dimensionless Trouton ratio, Tr ~ O(50), demonstrate that these fluids are highly
      extensional-thickening, providing a clear mechanism for the load-dampening
      properties of SF. The results also indicate the potential for utilizing the OSCER
      in screening of physiological SF samples, which will lead to improved
      understanding of, and therapies for, disease progression in arthritis sufferers. 

PMID- 24738011
TI  - Diffraction-limited ultrasensitive molecular nano-arrays with singular nano-cone
      scattering.
AB  - Large-library fluorescent molecular arrays remain limited in sensitivity (1 *
      10(6) molecules) and dynamic range due to background auto-fluorescence and
      scattering noise within a large (20-100 MUm) fluorescent spot. We report an
      easily fabricated silica nano-cone array platform, with a detection limit of 100
      molecules and a dynamic range that spans 6 decades, due to point (10 nm to 1 MUm)
      illumination of preferentially absorbed tagged targets by singular scattering off
      wedged cones. Its fluorescent spot reaches diffraction-limited submicron
      dimensions, which are 10(4) times smaller in area than conventional microarrays,
      with comparable reduction in detection limit and amplification of dynamic range. 

PMID- 24738013
TI  - Microfluidics platform for measurement of volume changes in immobilized
      intestinal enteroids.
AB  - Intestinal enteroids are ex vivo primary cultured single-layer epithelial cell
      spheroids of average diameter ~150 MUm with luminal surface facing inward.
      Measurement of enteroid swelling in response to secretagogues has been applied to
      genetic testing in cystic fibrosis and evaluation of drug candidates for cystic
      fibrosis and secretory diarrheas. The current measurement method involves manual
      addition of drugs and solutions to enteroids embedded in a Matrigel matrix and
      estimation of volume changes from confocal images of fluorescently stained
      enteroids. We developed a microfluidics platform for efficient trapping and
      immobilization of enteroids for quantitative measurement of volume changes.
      Multiple enteroids are trapped in a "pinball machine-like" array of
      polydimethylsiloxane posts for measurement of volume changes in unlabeled
      enteroids by imaging of an extracellular, high-molecular weight fluorescent dye.
      Measurement accuracy was validated using slowly expanding air bubbles. The method
      was applied to measure swelling of mouse jejunal enteroids in response to an
      osmotic challenge and cholera toxin-induced chloride secretion. The microfluidics
      platform allows for parallel measurement of volume changes on multiple enteroids
      during continuous superfusion, without an immobilizing matrix, and for
      quantitative volume determination without chemical labeling or assumptions about
      enteroid shape changes during swelling. 

PMID- 24738012
TI  - High-throughput particle separation and concentration using spiral inertial
      filtration.
AB  - A spiral inertial filtration (SIFT) device that is capable of high-throughput (1
      ml/min), high-purity particle separation while concentrating recovered target
      particles by more than an order of magnitude is reported. This device is able to
      remove large fractions of sample fluid from a microchannel without disruption of
      concentrated particle streams by taking advantage of particle focusing in
      inertial spiral microfluidics, which is achieved by balancing inertial lift
      forces and Dean drag forces. To enable the calculation of channel geometries in
      the SIFT microsystem for specific concentration factors, an equivalent circuit
      model was developed and experimentally validated. Large particle concentration
      factors were then achieved by maintaining either the average fluid velocity or
      the Dean number throughout the entire length of the channel during the
      incremental removal of sample fluid. The SIFT device was able to separate MCF7
      cells spiked into whole blood from the non-target white blood cells (WBC) with a
      recovery of nearly 100% while removing 93% of the sample volume, which resulted
      in a concentration enhancement of the MCF7 cancer cells by a factor of 14. 

PMID- 24738014
TI  - Modulating chemotaxis of lung cancer cells by using electric fields in a
      microfluidic device.
AB  - We employed direct-current electric fields (dcEFs) to modulate the chemotaxis of
      lung cancer cells in a microfluidic cell culture device that incorporates both
      stable concentration gradients and dcEFs. We found that the chemotaxis induced by
      a 0.5 MUM/mm concentration gradient of epidermal growth factor can be nearly
      compensated by a 360 mV/mm dcEF. When the effect of chemical stimulation was
      balanced by the electrical drive, the cells migrated randomly, and the path
      lengths were largely reduced. We also demonstrated electrically modulated
      chemotaxis of two types of lung cancer cells with opposite directions of
      electrotaxis in this device. 

PMID- 24738016
TI  - Nonunion of capitate due to late diagnosis in a teenager.
AB  - PATIENT: Male, 13 FINAL DIAGNOSIS: Isolated capitate bone fracture Symptoms: -
      MEDICATION: - Clinical Procedure: - Specialty: - OBJECTIVE: Unusual clinical
      course. BACKGROUND: Carpal fractures often appear in men under the age of 40
      years. Isolated fracture of the capitate without dislocation is very rare and
      comprises 1% of all carpal fractures. Nonunion of capitate mostly resulted from
      delay in diagnosis and lack of initial treatment. CASE REPORT: We reported the
      case of a 13-year-old boy who had a late-diagnosed capitate fracture. We put the
      wrist in a short-arm cast for 3 months. After the immobilization with the cast
      has been finalized, range of motion and strengthening exercises were started. One
      year after the trauma, we saw total union of the fracture. CONCLUSIONS: Diagnosis
      of carpal bone fracture may be missed, especially in skeletally immature
      patients. To prevent late diagnosis in skeletally immature patients, early
      control radiography should be taken. If further examination is needed, computed
      tomography should be performed. We can achieve good results with cast
      immobilization in this age group of patients. As a result, although the author
      has been advised surgical treatment for nonunion of capitate fracture,
      conservative treatment should be considered.

PMID- 24738015
TI  - Continuous size-based separation of microparticles in a microchannel with
      symmetric sharp corner structures.
AB  - A new microchannel with a series of symmetric sharp corner structures is reported
      for passive size-dependent particle separation. Micro particles of different
      sizes can be completely separated based on the combination of the inertial lift
      force and the centrifugal force induced by the sharp corner structures in the
      microchannel. At appropriate flow rate and Reynolds number, the centrifugal force
      effect on large particles, induced by the sharp corner structures, is stronger
      than that on small particles; hence after passing a series of symmetric sharp
      corner structures, large particles are focused to the center of the microchannel,
      while small particles are focused at two particle streams near the two side walls
      of the microchannel. Particles of different sizes can then be completely
      separated. Particle separation with this device was demonstrated using 7.32 MUm
      and 15.5 MUm micro particles. Experiments show that in comparison with the prior
      multi-orifice flow fractionation microchannel and multistage-multiorifice flow
      fractionation microchannel, this device can completely separate two-size
      particles with narrower particle stream band and larger separation distance
      between particle streams. In addition, it requires no sheath flow and complex
      multi-stage separation structures, avoiding the dilution of analyte sample and
      complex operations. The device has potentials to be used for continuous, complete
      particle separation in a variety of lab-on-a-chip and biomedical applications. 

PMID- 24738017
TI  - Efficacy of a low dose of estrogen on antioxidant defenses and heart rate
      variability.
AB  - This study tested whether a low dose (40% less than the pharmacological dose of
      17-beta estradiol) would be as effective as the pharmacological dose to improve
      cardiovascular parameters and decrease cardiac oxidative stress. Female Wistar
      rats (n = 9/group) were divided in three groups: (1) ovariectomized (Ovx), (2)
      ovariectomized animals treated for 21 days with low dose (LE; 0.2 mg), and (3)
      high dose (HE; 0.5 mg) 17-beta estradiol subcutaneously. Hemodynamic assessment
      and spectral analysis for evaluation of autonomic nervous system regulation were
      performed. Myocardial superoxide dismutase (SOD) and catalase (CAT) activities,
      redox ratio (GSH/GSSG), total radical-trapping antioxidant potential (TRAP),
      hydrogen peroxide, and superoxide anion concentrations were measured. HE and LE
      groups exhibited an improvement in hemodynamic function and heart rate
      variability. These changes were associated with an increase in the TRAP,
      GSH/GSSG, SOD, and CAT. A decrease in hydrogen peroxide and superoxide anion was
      also observed in the treated estrogen groups as compared to the Ovx group. Our
      results indicate that a low dose of estrogen is just as effective as a high dose
      into promoting cardiovascular function and reducing oxidative stress, thereby
      supporting the approach of using low dose of estrogen in clinical settings to
      minimize the risks associated with estrogen therapy.

PMID- 24738018
TI  - The protective effects of Shen-Fu injection on experimental acute pancreatitis in
      a rat model.
AB  - OBJECTIVES: In the present study, we investigated the protective effects of Shen
      Fu injection (SFI) on a caerulein-induced rat pancreatitis (AP) model. METHODS:
      SFI was given to rats in the SFI treated group through intraperitoneal injection.
      Blood and pancreas samples were collected for serological and histopathological
      studies. RESULTS: Our results showed that AP caused significant decrease in
      tissue glutathione (GSH) and serum IL-4 and IL-10, while pancreatic
      malondialdehyde (MDA) and myeloperoxidase (MPO) were increased. Furthermore, TNF
      alpha, IL-1beta, amylase, and lipase levels were also significantly increased. On
      the other hand, SFI treatment reserved all these biochemical indices as well as
      histopathologic alterations that were induced by caerulein. CONCLUSION: Our
      findings suggest that the SFI protects against caerulein-induced AP in rats via
      modulation of cytokines, oxidative stress, and Nuclear Factor-kappa B (NF-kappaB)
      activity.

PMID- 24738019
TI  - Pegylated G-CSF inhibits blood cell depletion, increases platelets, blocks
      splenomegaly, and improves survival after whole-body ionizing irradiation but not
      after irradiation combined with burn.
AB  - Exposure to ionizing radiation alone (radiation injury, RI) or combined with
      traumatic tissue injury (radiation combined injury, CI) is a crucial life
      threatening factor in nuclear and radiological accidents. As demonstrated in
      animal models, CI results in greater mortality than RI. In our laboratory, we
      found that B6D2F1/J female mice exposed to (60)Co-gamma-photon radiation followed
      by 15% total-body-surface-area skin burns experienced an increment of 18% higher
      mortality over a 30-day observation period compared to irradiation alone; that
      was accompanied by severe cytopenia, thrombopenia, erythropenia, and anemia. At
      the 30th day after injury, neutrophils, lymphocytes, and platelets still remained
      very low in surviving RI and CI mice. In contrast, their RBC, hemoglobin, and
      hematocrit were similar to basal levels. Comparing CI and RI mice, only RI
      induced splenomegaly. Both RI and CI resulted in bone marrow cell depletion. It
      was observed that only the RI mice treated with pegylated G-CSF after RI resulted
      in 100% survival over the 30-day period, and pegylated G-CSF mitigated RI-induced
      body-weight loss and depletion of WBC and platelets. Peg-G-CSF treatment
      sustained RBC balance, hemoglobin levels, and hematocrits and inhibited
      splenomegaly after RI. The results suggest that pegylated G-CSF effectively
      sustained animal survival by mitigating radiation-induced cytopenia,
      thrombopenia, erythropenia, and anemia.

PMID- 24738020
TI  - Resveratrol inhibits phenotype modulation by platelet derived growth factor-bb in
      rat aortic smooth muscle cells.
AB  - Dedifferentiated vascular smooth muscle cells (VSMCs) are phenotypically
      modulated from the contractile state to the active synthetic state in the vessel
      wall. In this study, we investigated the effects of resveratrol on phenotype
      modulation by dedifferentiation and the intracellular signal transduction
      pathways of platelet derived growth factor-bb (PDGF-bb) in rat aortic vascular
      smooth muscle cells (RAOSMCs). Treatment of RAOSMCs with resveratrol showed dose
      dependent inhibition of PDGF-bb-stimulated proliferation. Resveratrol treatment
      inhibited this phenotype change and disassembly of actin filaments and maintained
      the expression of contractile phenotype-related proteins such as calponin and
      smooth muscle actin-alpha in comparison with only PDGF-bb stimulated RAOSMC.
      Although PDGF stimulation elicited strong and detectable Akt and mTOR
      phosphorylations lasting for several hours, Akt activation was much weaker when
      PDGF was used with resveratrol. In contrast, resveratrol only slightly inhibited
      phosphorylations of 42/44 MAPK and p38 MAPK. In conclusion, RAOSMC
      dedifferentiation, phenotype, and proliferation rate were inhibited by
      resveratrol via interruption of the balance of Akt, 42/44MAPK, and p38MAPK
      pathway activation stimulated by PDGF-bb. 

PMID- 24738021
TI  - Human serum albumin Cys34 oxidative modifications following infiltration in the
      carotid atherosclerotic plaque.
AB  - OBJECTIVES: To evaluate if the prooxidant environment present in atherosclerotic
      plaque may oxidatively modify filtered albumin. METHODS: Fluorescein-5-maleimide
      labelled plasma samples and plaque extracts from 27 patients who had undergone
      carotid endarterectomy were analysed through nonreducing SDS-PAGE for albumin
      Cys(34) oxidation. Furthermore, degree and pattern of S-thiolation in both
      circulating and plaque-filtered albumin were assayed. RESULTS: Albumin filtered
      in the atherosclerotic plaque showed higher levels of Cys(34) oxidative
      modifications than the corresponding circulating form as well as different
      patterns of S-thiolation. CONCLUSIONS: Data indicate that the circulating
      albumin, once filtered in plaque, undergoes Cys(34) oxidative modifications and
      demonstrate for the first time that albumin is a homocysteine and
      cysteinylglycine vehicle inside the plaque environment.

PMID- 24738023
TI  - SET domain-containing Protein 4 (SETD4) is a Newly Identified Cytosolic and
      Nuclear Lysine Methyltransferase involved in Breast Cancer Cell Proliferation.
AB  - Cancer is comprised of a multitude of epigenetic abnormalities, including the
      global loss and regional gain of DNA methylation as well as alterations in
      histone methylation. Here, we characterize a new methyltransferase, SET domain
      containing protein 4 (SETD4), which is involved in breast carcinogenesis.
      Quantitative real-time PCR (qPCR) showed elevated expression levels of SETD4 in
      several breast cancer cell lines. SETD4 overexpression was confirmed by western
      blot analysis suggesting a correlation between high expression of SETD4 and a
      lack of the estrogen receptor (ER) in breast cancer. In addition, cell
      fractionation studies and confocal immunofluorescence revealed the nuclear and
      non-nuclear localization of this new protein. SETD4 knockdown in breast cancer
      cell lines significantly suppressed their proliferation and delayed the G1/S cell
      cycle transition without affecting apoptosis. Furthermore, western blot analysis
      showed that knockdown of SETD4 decreased cyclin D1 expression, revealing the
      involvement of SETD4 in cell cycle regulation. These data imply that SETD4 plays
      a crucial role in breast carcinogenesis and could be a novel molecular target for
      the development of new strategies for the diagnosis and treatment of breast
      cancer.

PMID- 24738022
TI  - Effects of consumption of rooibos (Aspalathus linearis) and a rooibos-derived
      commercial supplement on hepatic tissue injury by tert-butyl hydroperoxide in
      Wistar rats.
AB  - This study investigated the antioxidative effect of rooibos herbal tea and a
      rooibos-derived commercial supplement on tert-butyl hydroperoxide- (t-BHP-)
      induced oxidative stress in the liver. Forty male Wistar rats consumed fermented
      rooibos, unfermented rooibos, a rooibos-derived commercial supplement, or water
      for 10 weeks, while oxidative stress was induced during the last 2 weeks via
      intraperitoneal injection of 30 umole of t-BHP per 100 g body weight. None of the
      beverages impaired the body weight gain of the respective animals. Rats consuming
      the rooibos-derived commercial supplement had the highest (P < 0.05) daily total
      polyphenol intake (169 mg/day) followed by rats consuming the unfermented rooibos
      (93.4 mg/day) and fermented rooibos (73.1 mg/day). Intake of both the derived
      supplement and unfermented rooibos restored the t-BHP-induced reduction and
      increased (P < 0.05) the antioxidant capacity status of the liver, while not
      impacting on lipid peroxidation. The rooibos herbal tea did not affect the
      hepatic antioxidant enzymes, except fermented rooibos that caused a decrease (P <
      0.05) in superoxide dismutase activity. This study confirms rooibos herbal tea as
      good dietary antioxidant sources and, in conjunction with its many other
      components, offers a significantly enhanced antioxidant status of the liver in an
      induced oxidative stress situation.

PMID- 24738024
TI  - Adolescent physical activity and endometriosis risk.
AB  - BACKGROUND: In the one study examining the relationship, adolescent physical
      activity was not associated with risk for endometriosis. Case-control studies
      have shown 40-80% reductions in risk for adult activity, while only an 11%
      reduction in endometriosis risk was observed in a recent prospective analysis.
      METHODS: Using data collected from the Nurses' Health Study II, a prospective
      cohort study of premenopausal US nurses that began in 1989, we have attempted to
      clarify this relation. Data are updated every 2 yrs with follow-up for these
      analyses through to 2001. Women reported the average amount of time per week
      spent in moderate and strenuous recreational activity during three age periods:
      ages 12-13, ages 14-17, and ages 18-22. A metabolic equivalent (MET) score was
      assigned to each activity and these were summed to estimate total activity.
      RESULTS: During 637,747 person-years of follow-up, 1,481 cases of
      laparoscopically confirmed endometriosis were reported among women with no past
      infertility. After adjusting for age, calendar time, birth weight, age at
      menarche, parity, oral contraceptive use, and body mass index (BMI), we observed
      a 16% increase in the risk for endometriosis comparing the greatest amount of
      activity (>=80 MET-h/wk) with the least (<20 MET-h/wk) during ages 12-13
      (RR=1.16, 95% CI=0.98-1.37, p-value test for trend=0.02), and no associations for
      ages 14-17 or ages 18-22. In analyses of the individual activity types within
      each time period, only strenuous activity during ages 12-13 was associated with
      endometriosis. CONCLUSIONS: We did not find evidence of a beneficial association
      between adolescent physical activity and laparoscopically confirmed
      endometriosis, but in fact found a small increase in risk.

PMID- 24738025
TI  - Molteno3 implantation as primary glaucoma surgery.
AB  - Purpose. To determine the outcome of Molteno3 implantation as primary glaucoma
      surgery and to analyze the factors influencing the surgical outcome. Methods.
      This is a retrospective clinical study of 106 consecutive eyes (97 patients) with
      no previous glaucoma surgery. Surgical failure was defined as an IOP > 21 mmHg or
      less than a 20% reduction below baseline, or IOP <= 5 mmHg, on two consecutive
      visits after 3 months follow-up, or reoperation for glaucoma or loss of light
      perception. Results. At the end of the follow-up (mean, 35 months; range, 12-71
      months), the mean postoperative IOP (14.2 +/- 4.4 mmHg) was statistically
      significantly lower than the preoperative IOP (35.2 +/- 9.7 mmHg) (P < 0.001).
      Life-table success rates were 97%, 94%, and 91% after follow-up of 12, 24, and 36
      months, respectively. Success rate for an IOP <= 18 mmHg was 77% at the last
      visit. Success was not influenced by previous cataract surgery, sex, age, laser
      trabeculoplasty (LTP), preoperative IOP, or number of antiglaucoma medications.
      Forty-seven eyes had 66 postoperative complications. Conclusions. The primary
      Molteno3 implant provided significant IOP lowering with minimal and manageable
      complications in uncontrolled glaucoma. Neither previous cataract surgery nor LTP
      had any detrimental effect on surgical success. 

PMID- 24738026
TI  - Is exergaming a viable tool in the fight against childhood obesity?

PMID- 24738027
TI  - Predictors of weight loss maintenance following an insurance-sponsored weight
      management program.
AB  - Intentional weight loss among overweight and obese adults (body mass index >= 25
      kg/m(2)) is associated with numerous health benefits, but weight loss maintenance
      (WLM) following participation in weight management programming has proven to be
      elusive. Many individuals attempting to lose weight join formal programs,
      especially women, but these programs vary widely in focus, as do postprogram
      weight regain results. We surveyed 2,106 former participants in a community
      based, insurance-sponsored weight management program in the United States to
      identify the pre, during, and post-intervention behavioral and psychosocial
      factors that lead to successful WLM. Of 835 survey respondents (39.6% response
      rate), 450 met criteria for inclusion in this study. Logistic regression analyses
      suggest that interventionists should assess and discuss weight loss and behavior
      change perceptions early in a program. However, in developing maintenance plans
      later in a program, attention should shift to behaviors, such as weekly weighing,
      limiting snacking in the evening, limiting portion sizes, and being physically
      active every day.

PMID- 24738028
TI  - Regional failures after selective neck dissection in previously untreated
      squamous cell carcinoma of oral cavity.
AB  - AIM: To share experience with regional failures after selective neck dissection
      in both node negative and positive previously untreated patients diagnosed with
      squamous cell carcinoma of the oral cavity. PATIENTS AND METHODS: Data of 219
      patients who underwent SND at Shaukat Khanum Cancer Hospital from 2003 to 2010
      were retrospectively reviewed. Patient characteristics, treatment modalities, and
      regional failures were assessed. Expected 5-year regional control was calculated
      and prognostic factors were determined. RESULTS: Median follow-up was 29 (9-109)
      months. Common sites were anterior tongue in 159 and buccal mucosa in 22
      patients. Pathological nodal stage was N0 in 114, N1 in 32, N2b in 67, and N2c in
      5 patients. Fourteen (6%) patients failed in clinically node negative neck while
      8 (4%) failed in clinically node positive patients. Out of 22 total regional
      failures, primary tumor origin was from tongue in 16 (73%) patients. Expected 5
      year regional control was 95% and 81% for N0 and N+ disease, respectively (P <
      0.0001). Only 13% patients with well differentiated, T1 tumors in cN0 neck were
      pathologically node positive. CONCLUSIONS: Selective neck dissection yields
      acceptable results for regional management of oral squamous cell carcinoma. Wait
      and see policy may be effective in a selected subgroup of patients.

PMID- 24738029
TI  - Laparoscopic appendectomy in children: experience in a single centre in
      chittagong, bangladesh.
AB  - Background. Since the latter half of 1980s laparoscopy has become a well accepted
      modality in children in many surgical procedures including appendectomy. We
      present here the experience of laparoscopic appendectomy in children in a
      tertiary care hospital in Bangladesh.  Subjects & Methods. From October 7, 2005
      to July 31, 2012, 1809 laparoscopic appendectomies were performed. Laparoscopy
      was performed in all the cases using 3 ports. For difficult and adherent cases
      submucosal appendectomy was performed. Feeding was allowed 6 h after surgery and
      the majority was discharged on the first postoperative day. The age, sex,
      operative techniques, operative findings, operative time, hospital stay, outcome,
      and complications were evaluated in this retrospective study. Results. Mean age
      was 8.17 +/- 3.28 years and 69% were males. Fifteen percent were complicated
      appendicitis, 8 cases needed conversion, and 27 cases were done by submucosal
      technique. Mean operating time was 39.8 +/- 14.2 minutes and mean postoperative
      hospital stay was 1.91 days. About 5% cases had postoperative complications
      including 4 intra-abdominal abscesses. Conclusions. Laparoscopic appendectomy is
      a safe procedure in children even in complicated cases. 

PMID- 24738030
TI  - Clinical Outcomes for Breast Cancer Patients Undergoing Mastectomy and
      Reconstruction with Use of DermACELL, a Sterile, Room Temperature Acellular
      Dermal Matrix.
AB  - Background. Decellularized human skin has been used in a variety of medical
      applications, primarily involving soft tissue reconstruction, wound healing, and
      tendon augmentation. Theoretically, decellularization removes potentially
      immunogenic material and provides a clean scaffold for cellular and vascular in
      growth. The use of acellular dermal matrix in two-stage postmastectomy breast
      reconstruction is described. Methods. Ten consecutive breast cancer patients were
      treated with mastectomies and immediate reconstruction from August to November
      2011. There were 8 bilateral and 1 unilateral mastectomies for a total of 17
      breasts, with one exclusion for chronic tobacco use. Reconstruction included the
      use of a new 6 * 16 cm sterile, room temperature acellular dermal matrix patch
      (DermACELL) soaked in a cefazolin bath. Results. Of the 17 breasts, 15
      reconstructions were completed; 14 of them with expander to implant sequence and
      acellular dermal matrix. Histological analysis of biopsies obtained during
      trimming of the matrix at the second stage appeared nonremarkable with evidence
      of normal healing, cellularity, and vascular infiltration. Conclusion.
      Postoperative observations showed that this cellular dermal matrix appears to be
      an appropriate adjunct to reconstruction with expanders. This acellular dermal
      matrix appeared to work well with all patients, even those receiving
      postoperative chemotherapy, postoperative radiation, prednisone, or warfarin
      sodium. 

PMID- 24738031
TI  - Tuberculin Skin Tests versus Interferon-Gamma Release Assays in Tuberculosis
      Screening among Immigrant Visa Applicants.
AB  - Objective. Use of tuberculin skin tests (TSTs) and interferon gamma release
      assays (IGRAs) as part of tuberculosis (TB) screening among immigrants from high
      TB-burden countries has not been fully evaluated. Methods. Prevalence of
      Mycobacterium tuberculosis infection (MTBI) based on TST, or the QuantiFERON-TB
      Gold test (QFT-G), was determined among immigrant applicants in Vietnam bound for
      the United States (US); factors associated with test results and discordance were
      assessed; predictive values of TST and QFT-G for identifying chest radiographs
      (CXRs) consistent with TB were calculated. Results. Of 1,246 immigrant visa
      applicants studied, 57.9% were TST positive, 28.3% were QFT-G positive, and test
      agreement was 59.4%. Increasing age was associated with positive TST results,
      positive QFT-G results, TST-positive but QFT-G-negative discordance, and abnormal
      CXRs consistent with TB. Positive predictive values of TST and QFT-G for an
      abnormal CXR were 25.9% and 25.6%, respectively. Conclusion. The estimated
      prevalence of MTBI among US-bound visa applicants in Vietnam based on TST was
      twice that based on QFT-G, and 14 times higher than a TST-based estimate of MTBI
      prevalence reported for the general US population in 2000. QFT-G was not better
      than TST at predicting abnormal CXRs consistent with TB. 

PMID- 24738032
TI  - Adaptation of Sonication-Assisted Matrix Solid Phase Dispersion of Tissues for
      the Subsequent Extraction of Polycyclic Aromatic Hydrocarbons from Gulf Menhaden
      (Brevoortia patronus).
AB  - A new adaptation based on matrix solid phase dispersion of tissue for the
      subsequent isolation of polycyclic aromatic hydrocarbons was developed and used
      for extractions of Gulf menhaden caught during the summer of 2011. Many Matrix
      Solid Phase Dispersion (MSPD) methods require specific cartridges and other clean
      up materials in order to achieve proper extraction. For this study, the tissues
      were lyophilized prior to applying the adapted MSPD method allowing for a much
      more complete homogenization with the C18 silica. The tissue was spiked with
      phenanthrene d10 as a surrogate as a measure of PAH recovery prior to the
      lyophilisation process to determine if any target compounds were lost and prior
      to sonication as per the finalized adaptation procedure to determine method
      efficiency. This technique used C18 silica in a 1 : 1 ratio as the primary
      homogenizing material for the menhaden tissue matrix and was eluted with
      dichloromethane (DCM) until visibly clear. The overall study mean recovery was
      88% +/- 5% with method detection limits between 0.4 ng/g and 4.4 ng/g tissue dry
      weight. This adapted protocol has been used exclusively on the analysis of high
      lipid content fish stocks affected by dispersed and weathered oil from the BP
      Horizon incident. 

PMID- 24738033
TI  - Can morning rise in salivary cortisol be a biological parameter in an
      occupational rehabilitation clinic? A feasibility study.
AB  - Objective. To test the feasibility of measuring salivary cortisol in an inpatient
      clinic for occupational rehabilitation, and cortisol as a biological parameter.
      Methods. In 17 patients in vocational rehabilitation, cortisol in saliva was
      measured at awakening, 30 min after and before bedtime. The cortisol measures
      were taken on day 2 and day 22 of the rehabilitation period. Cortisol awakening
      response was estimated in absolute value and as percent rise of the value at
      awakening. Results. The cortisol awakening response in absolute value was 6.7 (SD
      = 4.9) nmol/L on day 2 and 2.7 (SD = 5.6) nmol/L on day 22. The change was not
      statistically significant. The mean value for cortisol morning rise calculated in
      percent was 186% on day 2 and 51% on day 22. Conclusion. It is possible to
      conduct a clinical study including salivary cortisol in a rehabilitation clinic.
      This study indicates that cortisol morning rise may be a useful biological
      parameter for effect of intervention in a rehabilitation clinic; this remains to
      be tested in a larger population. 

PMID- 24738034
TI  - A fused maxillary central incisor and its multidisciplinary treatment: an 18-year
      follow-up.
AB  - Fused teeth may cause aesthetic, spacing, periodontal, eruption, and caries
      problems. The present case report describes a 7-year-old boy patient with a chief
      complaint of unerupted maxillary incisor. Radiographic examination indicated a
      fused tooth which had two fused roots but two independent root canals. A complex
      management of a fused tooth is really difficult to standardize. In this case an
      orthodontic, endodontic, and surgical treatment (intentional replantation)
      allowed the tooth to be retained until 18 years following intervention.
      Maintenance of the root and alveolar bone in young adults at least until full
      skeletal maturation should be the main treatment objective. 

PMID- 24738036
TI  - Mechanistic considerations for the use of monoclonal antibodies for cancer
      therapy.
AB  - Since the approval of rituximab in 1997, monoclonal antibodies (mAbs) have become
      an increasingly important component of therapeutic regimens in oncology. The
      success of mAbs as a therapeutic class is a result of great strides that have
      been made in molecular biology and in biotechnology over the past several
      decades. Currently, there are 14 approved mAb products for oncology indications,
      and there are ten additional mAbs in late stages of clinical trials. Compared to
      traditional chemotherapeutic agents, mAbs have several advantages, including a
      long circulating half-life and high target specificity. Antibodies can serve as
      cytotoxic agents when administered alone, exerting a pharmacologic effect through
      several mechanisms involving the antigen binding (Fab) and/or Fc domains of the
      molecule, and mAbs may also be utilized as drug carriers, targeting a toxic
      payload to cancer cells. The extremely high affinity of mAbs for their targets,
      which is desirable with respect to pharmacodynamics (i.e., contributing to the
      high therapeutic selectivity of mAb), often leads to complex, non-linear, target
      mediated pharmacokinetics. In this report, we summarize the pharmacokinetic and
      pharmacodynamics of mAbs that have been approved and of mAbs that are near
      approval for oncology indications, with particular focus on the molecular and
      cellular mechanisms responsible for their disposition and efficacy. 

PMID- 24738035
TI  - Cancer metabolic reprogramming: importance, main features, and potentials for
      precise targeted anti-cancer therapies.
AB  - Cancer cells are well documented to rewire their metabolism and energy production
      networks to support and enable rapid proliferation, continuous growth, survival
      in harsh conditions, invasion, metastasis, and resistance to cancer treatments.
      Since Dr. Otto Warburg's discovery about altered cancer cell metabolism in 1930,
      thousands of studies have shed light on various aspects of cancer metabolism with
      a common goal to find new ways for effectively eliminating tumor cells by
      targeting their energy metabolism. This review highlights the importance of the
      main features of cancer metabolism, summarizes recent remarkable advances in this
      field, and points out the potentials to translate these scientific findings into
      life-saving diagnosis and therapies to help cancer patients. 

PMID- 24738037
TI  - pH-responsive mesoporous silica nanoparticles employed in controlled drug
      delivery systems for cancer treatment.
AB  - In the fight against cancer, controlled drug delivery systems have emerged to
      enhance the therapeutic efficacy and safety of anti-cancer drugs. Among these
      systems, mesoporous silica nanoparticles (MSNs) with a functional surface possess
      obvious advantages and were thus rapidly developed for cancer treatment. Many
      stimuli-responsive materials, such as nanoparticles, polymers, and inorganic
      materials, have been applied as caps and gatekeepers to control drug release from
      MSNs. This review presents an overview of the recent progress in the production
      of pH-responsive MSNs based on the pH gradient between normal tissues and the
      tumor microenvironment. Four main categories of gatekeepers can respond to acidic
      conditions. These categories will be described in detail. 

PMID- 24738038
TI  - Inhalation treatment of lung cancer: the influence of composition, size and shape
      of nanocarriers on their lung accumulation and retention.
AB  - OBJECTIVE: Various nanoparticles have been designed and tested in order to select
      optimal carriers for the inhalation delivery of anticancer drugs to the lungs.
      METHODS: THE FOLLOWING NANOCARRIERS WERE STUDIED: micelles, liposomes, mesoporous
      silica nanoparticles (MSNs), poly propyleneimine (PPI) dendrimer-siRNA complexes
      nanoparticles, quantum dots (QDs), and poly (ethylene glycol) polymers. All
      particles were characterized using the following methods: dynamic light
      scattering, zeta potential, atomic force microscopy, in vitro cyto- and
      genotoxicity. In vivo organ distribution of all nanoparticles, retention in the
      lungs, and anticancer effects of liposomes loaded with doxorubicin were examined
      in nude mice after the pulmonary or intravenous delivery. RESULTS: Significant
      differences in lung uptake were found after the inhalation delivery of lipid
      based and non-lipid-based nanoparticles. The accumulation of liposomes and
      micelles in lungs remained relatively high even 24 h after inhalation when
      compared with MSNs, QDs, and PPI dendrimers. There were notable differences
      between nanoparticle accumulation in the lungs and other organs 1 and 3 h after
      inhalation or intravenous administrations, but 24 h after intravenous injection
      all nanoparticles were mainly accumulated in the liver, kidneys, and spleen.
      Inhalation delivery of doxorubicin by liposomes significantly enhanced its
      anticancer effect and prevented severe adverse side effects of the treatment in
      mice bearing the orthotopic model of lung cancer. CONCLUSION: The results of the
      study demonstrate that lipid-based nanocarriers had considerably higher
      accumulation and longer retention time in the lungs when compared with non-lipid
      based carriers after the inhalation delivery. These particles are most suitable
      for effective inhalation treatment of lung cancer.

PMID- 24738039
TI  - Uptake of prostate cancer screening and associated factors among Chinese men aged
      50 or more: a population-based survey.
AB  - OBJECTIVE: To investigate the uptake rate of prostate specific antigen (PSA)
      testing among Hong Kong Chinese males aged 50 or above, and identify factors
      associated with the likelihood of undergoing a PSA test. METHODS: A population
      based telephone survey was conducted in Hong Kong in 2007. The survey covered
      demographic information, perceived health status, use of complementary therapy,
      cancer screening behavior, perceived susceptibility to cancer and family history
      of cancer. Descriptive statistics, percentages and logistic regression analysis
      were used for data analysis. RESULTS: A total of 1,002 men aged 50 or above took
      part in the study (response rate =67%), and the uptake rate of PSA testing was
      found to be 10%. Employment status, use of complementary therapy, perceiving
      regular visits to a doctor as good for health and the recommendations of health
      professionals were significant factors associated with PSA testing. CONCLUSION:
      The uptake rate of PSA testing in the study population was very low. Among all
      the factors identified, recommendations from health professionals had the
      strongest association with the uptake of PSA testing, and they should therefore
      take an active role in educating this population about cancer prevention and
      detection.

PMID- 24738040
TI  - Interferon-alpha-2b induces autophagy in hepatocellular carcinoma cells through
      Beclin1 pathway.
AB  - OBJECTIVE: To determine whether Interferon-alpha-2b (IFN-alpha2b) can modulate
      the autophagic response in hepatocellular carcinoma cells. METHODS:
      Hepatocellular carcinoma cells were treated with IFN-alpha2b. Autophagy was
      assessed by acridine orange staining, GFP-LC3 dotted assay, transmission electron
      microscopy and immunoblotting. RESULTS: Acridine orange staining showed that IFN
      alpha2b triggered the accumulation of acidic vesicular and autolysosomes in HepG2
      cells. The acridine orange HepG2 cell ratios were (4.3+/-1.0)%, (6.9+/-1.4)%, and
      (13.1+/-2.3)%, respectively, after treatment with 100, 1,000, and 10,000 IU/mL
      IFN-alpha2b for 48 h. A markedly punctate pattern was observed in HepG2 cells
      treated with 10,000 IU/mL IFN-alpha2b for 48 h, but only diffuse and weakly
      fluorescent GFP-LC3 puncta was observed in control cells. HepG2 cells treated
      with 10,000 IU/mL IFN-alpha2b for 48 h developed autophagosome-like
      characteristics, including single- or double-membrane vacuoles containing intact
      and degraded cellular debris. The Beclin1 and LC3-II protein expression was up
      regulated by IFN-alpha2b treatment. CONCLUSION: Autophagy can be induced in a
      dose-dependent manner by treatment with IFN-alpha2b in HepG2 cells, and the
      Beclin1 signaling pathway was stimulated by IFN-alpha2b.

PMID- 24738041
TI  - Quantification of small molecule drugs in biological tissue sections by imaging
      mass spectrometry using surrogate tissue-based calibration standards.
AB  - Quantitative analysis of administered drugs in biological tissues is essential
      for understanding the mechanisms underlying their efficacy or toxicity. Imaging
      mass spectrometry (IMS) may allow the quantification of targeted drugs in tissue
      sections along with the visualization of their spatial distribution. In this
      study, surrogate tissue-based calibration standards were prepared to quantify a
      small molecule drug (S-777469 or raclopride) in tissue sections of mice
      administered with the drug, followed by analysis with a linear ion trap mass
      spectrometer equipped with a matrix-assisted laser desorption/ionization (MALDI)
      source. The distribution of the drugs in the dissected organs was clearly
      visualized by MALDI-IMS. The drug concentration determined using the calibration
      standards prepared for MALDI-IMS analysis was highly consistent with that
      determined by liquid chromatography-tandem mass spectrometry, and the
      quantification in multiple organs was enabled. The results of this study show
      that MALDI-IMS can be used to quantify small molecule drugs in biological tissue
      sections using surrogate tissue-based calibration standards. 

PMID- 24738042
TI  - Statistical Analysis of Repeated MicroRNA High-Throughput Data with Application
      to Human Heart Failure: A Review of Methodology.
AB  - Complex experimental designs present unique challenges in the analysis of
      microRNA (miRNA) Cycle to Threshold (Ct) values. In this manuscript, we discuss
      various statistical techniques and their application in an analysis performed at
      the JG Brown Cancer Center. We consider data quality evaluation, data
      normalization, and statistical hypothesis procedures all in context of the
      example. The experiment utilized as the motivating example involved repeated
      sampling over time. The intra-subject correlation created by the repeated
      sampling should be incorporated into the analysis resulting in additional
      significant miRNAs. The statistical techniques leveraged to analyze miRNA Ct
      values resulting from qPCR should incorporate key features of the experimental
      design. It discusses potential issues with the commonly used methodologies when
      the experiment collects multiple samples from the same individuals over time.

PMID- 24738043
TI  - Nonalcoholic fatty liver disease and hepatocellular carcinoma.
AB  - Hepatocellular carcinoma (HCC) incidence is increasing worldwide in recent years.
      Most HCC cases develop in the presence of advanced chronic liver disease related
      to chronic hepatitis C virus (HCV) infection, chronic hepatitis B (HBV)
      infection, and alcohol abuse. Approximately 15-50% of HCC cases are classified as
      idiopathic, suggesting that other risk factors are responsible for its rising
      incidence. Recent studies suggest that nonalcoholic fatty liver disease (NAFLD)
      can be associated with these "idiopathic" cases. NAFLD progresses slowly and can
      develop into liver cirrhosis, liver failure, and HCC. In the last few years,
      NAFLD has received more attention because of its high prevalence worldwide. 

PMID- 24738045
TI  - Differential gene expression profiling of enriched human spermatogonia after
      short- and long-term culture.
AB  - This study aimed to provide a molecular signature for enriched adult human
      stem/progenitor spermatogonia during short-term (<2 weeks) and long-term culture
      (up to more than 14 months) in comparison to human testicular fibroblasts and
      human embryonic stem cells. Human spermatogonia were isolated by CD49f magnetic
      activated cell sorting and collagen(-)/laminin(+) matrix binding from primary
      testis cultures obtained from ten adult men. For transcriptomic analysis, single
      spermatogonia-like cells were collected based on their morphology and dimensions
      using a micromanipulation system from the enriched germ cell cultures.
      Immunocytochemical, RT-PCR and microarray analyses revealed that the analyzed
      populations of cells were distinct at the molecular level. The germ- and
      pluripotency-associated genes and genes of differentiation/spermatogenesis
      pathway were highly expressed in enriched short-term cultured spermatogonia.
      After long-term culture, a proportion of cells retained and aggravated the
      "spermatogonial" gene expression profile with the expression of germ and
      pluripotency-associated genes, while in the majority of long-term cultured cells
      this molecular profile, typical for the differentiation pathway, was reduced and
      more genes related to the extracellular matrix production and attachment were
      expressed. The approach we provide here to study the molecular status of in vitro
      cultured spermatogonia may be important to optimize the culture conditions and to
      evaluate the germ cell plasticity in the future. 

PMID- 24738046
TI  - Comparison of the ventricle muscle proteome between patients with rheumatic heart
      disease and controls with mitral valve prolapse: HSP 60 may be a specific protein
      in RHD.
AB  - OBJECTIVE: Rheumatic heart disease (RHD) is a serious autoimmune heart disease.
      The present study was aimed at identifying the differentially expressed proteins
      between patients with RHD and controls with mitral valve prolapse. METHODS: Nine
      patients with RHD and nine controls with mitral valve prolapsed were enrolled for
      this study. Two-dimensional difference in-gel electrophoresis (2D-DIGE) and
      matrix-assisted laser desorption ionization time-of-flight mass spectrometry
      (MALDI-TOF-MS) were performed. RESULTS: A total of 39 protein spots with
      differential expressions were identified between the two groups (P < 0.05,
      Average Ratio > 1.2 or Average Ratio < -1.2) and four upregulated proteins
      (including heat shock protein 60 (HSP 60), desmin, PDZ and LIM domain protein 1,
      and proteasome subunit alpha type-1) and three downregulated proteins (including
      tropomyosin alpha-1 chain, malate dehydrogenase, and chaperone activity of bc1
      complex homolog) were determined. CONCLUSION: These seven proteins, especially
      HSP 60, may serve as potential biomarkers for the diagnosis of RHD and provide
      evidence to explain the mechanisms of this complex disease in the future.

PMID- 24738044
TI  - The role(s) of cytokines/chemokines in urinary bladder inflammation and
      dysfunction.
AB  - Bladder pain syndrome (BPS)/interstitial cystitis (IC) is a chronic pain syndrome
      characterized by pain, pressure, or discomfort perceived to be bladder related
      and with at least one urinary symptom. It was recently concluded that 3.3-7.9
      million women (>18 years old) in the United States exhibit BPS/IC symptoms. The
      impact of BPS/IC on quality of life is enormous and the economic burden is
      significant. Although the etiology and pathogenesis of BPS/IC are unknown,
      numerous theories including infection, inflammation, autoimmune disorder, toxic
      urinary agents, urothelial dysfunction, and neurogenic causes have been proposed.
      Altered visceral sensations from the urinary bladder (i.e., pain at low or
      moderate bladder filling) that accompany BPS/IC may be mediated by many factors
      including changes in the properties of peripheral bladder afferent pathways such
      that bladder afferent neurons respond in an exaggerated manner to normally
      innocuous stimuli (allodynia). The goals for this review are to describe
      chemokine/receptor (CXCL12/CXCR4; CCL2/CCR2) signaling and cytokine/receptor
      (transforming growth factor (TGF-beta)/TGF-beta type 1 receptor) signaling that
      may be valuable LUT targets for pharmacologic therapy to improve urinary bladder
      function and reduce somatic sensitivity associated with urinary bladder
      inflammation.

PMID- 24738047
TI  - Studies on the antidiabetic activities of Cordyceps militaris extract in diet
      streptozotocin-induced diabetic Sprague-Dawley rats.
AB  - Due to substantial morbidity and high complications, diabetes mellitus is
      considered as the third "killer" in the world. A search for alternative
      antidiabetic drugs from herbs or fungi is highly demanded. Our present study aims
      to investigate the antidiabetic activities of Cordyceps militaris on diet
      streptozotocin-induced type 2 diabetes mellitus in rats. Diabetic rats were
      orally administered with water extract or alcohol extract at 0.05 g/kg and 2 g/kg
      for 3 weeks, and then, the factors levels related to blood glucose, lipid, free
      radicals, and even nephropathy were determined. Pathological alterations on liver
      and kidney were examined. Data showed that, similar to metformin, Cordyceps
      militaris extracts displayed a significant reduction in blood glucose levels by
      promoting glucose metabolism and strongly suppressed total cholesterol and
      triglycerides concentration in serum. Cordyceps militaris extracts exhibit
      antioxidative effects indicated by normalized superoxide dismutase and
      glutathione peroxidase levels. The inhibitory effects on blood urea nitrogen,
      creatinine, uric acid, and protein revealed the protection of Cordyceps militaris
      extracts against diabetic nephropathy, which was confirmed by pathological
      morphology reversion. Collectively, Cordyceps militaris extract, a safe
      pharmaceutical agent, presents excellent antidiabetic and antinephropathic
      activities and thus has great potential as a new source for diabetes treatment.

PMID- 24738048
TI  - Decreasing quality of the new generations of anti-Mullerian hormone assays.
AB  - Anti-Mullerian hormone (AMH) measurements are widely used to optimize the
      stimulation protocols. First generation AMH kits correlated well with ovarian
      reserve and response to stimulation. In the present study we aimed to asses if
      the new generation kits share the same accurate correlations. Retrospective data
      were collected from 8323 blood samples. For comparison we used Immunotech I
      generation kit (ImI 4035 samples), Beckman Coulter II generation kit RUO (BCII
      RUO 3449, samples) and Beckman Coulter II generation kit with IVD certificate
      (BCII IVD 839 samples). We compared average AMH concentrations measured with
      different kits, as well as correlation between kits. We also compared average AMH
      concentrations in sera collected on different cycle days and samples of different
      quality of preservation. AMH serum concentrations differed for each kit, ranging
      4.4 +/- 4.12 (mean +/- SD) for the ImI, 2.68 +/- 3.15 for the BCII RUO, and 1.64
      +/- 2.85 for BCII IVD. The mean differences from an adjusted regression model
      were -48.7%, -40%, and -69.2%, respectively. In conclusion, the changes of the BC
      AMH kits are unpredictable; however, the improvement of them is still possible.
      It would be very dangerous to use elaborated stimulation protocol (based on the
      Ist generation AMH results) with the results from the IInd generation assays. 

PMID- 24738049
TI  - Fear processing in dental phobia during crossmodal symptom provocation: an fMRI
      study.
AB  - While previous studies successfully identified the core neural substrates of the
      animal subtype of specific phobia, only few and inconsistent research is
      available for dental phobia. These findings might partly relate to the fact that,
      typically, visual stimuli were employed. The current study aimed to investigate
      the influence of stimulus modality on neural fear processing in dental phobia.
      Thirteen dental phobics (DP) and thirteen healthy controls (HC) attended a block
      design functional magnetic resonance imaging (fMRI) symptom provocation paradigm
      encompassing both visual and auditory stimuli. Drill sounds and matched neutral
      sinus tones served as auditory stimuli and dentist scenes and matched neutral
      videos as visual stimuli. Group comparisons showed increased activation in the
      insula, anterior cingulate cortex, orbitofrontal cortex, and thalamus in DP
      compared to HC during auditory but not visual stimulation. On the contrary, no
      differential autonomic reactions were observed in DP. Present results are largely
      comparable to brain areas identified in animal phobia, but also point towards a
      potential downregulation of autonomic outflow by neural fear circuits in this
      disorder. Findings enlarge our knowledge about neural correlates of dental phobia
      and may help to understand the neural underpinnings of the clinical and
      physiological characteristics of the disorder. 

PMID- 24738051
TI  - Accumulation of heavy metals in crayfish and fish from selected Czech reservoirs.
AB  - To evaluate the accumulation of aluminium, cadmium, chromium, copper, lead,
      mercury, nickel, and zinc in crayfish and fish organ tissues, specimens from
      three drinking water reservoirs (Boskovice, Landstejn, and Nova Rise) and one
      contaminated site (Darkovske more) in the Czech Republic were examined. Crayfish
      hepatopancreas was confirmed to be the primary accumulating site for the majority
      of metals (Cu > Zn > Ni > Cd > Cr), while Hg and Cr were concentrated in
      abdominal muscle, and Al and Pb were concentrated in gill. Metals found in Nova
      Rise specimens included Cu > Zn > Ni and those found in Boskovice included Zn >
      Hg > Cr. Cd concentrations were observed only in Landstejn specimens, while
      contaminated Darkovske more specimens showed the highest levels of accumulation
      (Cu > Al > Zn > Pb). The majority of evaluated metals were found in higher
      concentrations in crayfish: Cu > Al > Zn > Ni > Cr > Cd > Pb, with Hg being the
      only metal accumulating higher in fish. Due to accumulation similarities of Al in
      crayfish and fish gill, differences of Hg in muscle, and features noted for the
      remaining metals in examined tissues, biomonitoring should incorporate both
      crayfish and fish to produce more relevant water quality surveys. 

PMID- 24738050
TI  - Snake venom L-amino acid oxidases: trends in pharmacology and biochemistry.
AB  - L-amino acid oxidases are enzymes found in several organisms, including venoms of
      snakes, where they contribute to the toxicity of ophidian envenomation. Their
      toxicity is primarily due to enzymatic activity, but other mechanisms have been
      proposed recently which require further investigation. L-amino acid oxidases
      exert biological and pharmacological effects, including actions on platelet
      aggregation and the induction of apoptosis, hemorrhage, and cytotoxicity. These
      proteins present a high biotechnological potential for the development of
      antimicrobial, antitumor, and antiprotozoan agents. This review provides an
      overview of the biochemical properties and pharmacological effects of snake venom
      L-amino acid oxidases, their structure/activity relationship, and supposed
      mechanisms of action described so far. 

PMID- 24738052
TI  - A novel strategy for inducing the antitumor effects of triterpenoid compounds:
      blocking the protumoral functions of tumor-associated macrophages via STAT3
      inhibition.
AB  - There are many types of nontumor cells, including leukocytes, fibroblasts, and
      endothelial cells, in the tumor microenvironment. Among these cells, infiltrating
      macrophages have recently received attention as novel target cells due to their
      protumoral functions. Infiltrating macrophages are called tumor-associated
      macrophages (TAMs). TAMs polarized to the M2 phenotype are involved in tumor
      development and are associated with a poor clinical prognosis. Therefore, the
      regulation of TAM activation or M2 polarization is a new strategy for antitumor
      therapy. We screened natural compounds possessing an inhibitory effect on the M2
      polarization of human macrophages. Among 200 purified natural compounds examined,
      corosolic acid (CA) and oleanolic acid (OA), both are categorized in triterpenoid
      compounds, inhibited macrophage polarization to M2 phenotype by suppressing STAT3
      activation. CA and OA also directly inhibited tumor cell proliferation and
      sensitized tumor cells to anticancer drugs, such as adriamycin and cisplatin. The
      in vivo experiments showed that CA significantly suppressed subcutaneous tumor
      development and lung metastasis in a murine sarcoma model. The application of
      triterpenoid compounds, such as CA and OA, is a potential new anticancer therapy
      targeting macrophage activation, with synergistic effects with anticancer agents.

PMID- 24738053
TI  - A standardized critical size defect model in normal and osteoporotic rats to
      evaluate bone tissue engineered constructs.
AB  - Tissue engineered constructs should be tested for their efficacy not only in
      normal but also in osteoporotic bone. The rat is an established animal model for
      osteoporosis and is used often for bone healing studies. In this study a defined
      and standardized critical size defect model in the rat suitable for screening new
      tissue engineered constructs in normal and osteoporotic bone is described and
      validated. Normal and ovariectomised Wistar rats received a unilateral
      middiaphyseal 5 mm defect in the femur, which was instrumented with a radiolucent
      PEEK plate fixed with angular stable titanium screws and left untreated. All
      animals were euthanized eight weeks after defect surgery and the bone healing was
      evaluated using radiographs, computed tomography measurements, and histology. The
      developed fixation system provided good stability, even in osteoporotic bone. The
      implants and ancillary instruments ensured consistent and facile placement of the
      PEEK plates. The untreated defects did not heal without intervention making the
      model a well-defined and standardized critical size defect model highly useful
      for evaluating tissue engineered solutions in normal and osteoporotic bone.

PMID- 24738054
TI  - A purified recombinant lipopeptide as adjuvant for cancer immunotherapy.
AB  - Synthetic lipopeptides have been widely used as vaccine adjuvants to enhance
      immune responses. The present study demonstrated that the tryptic N-terminal
      fragment of the lipoprotein rlipo-D1E3 (lipo-Nter) induces superior antitumor
      effects compared to a synthetic lipopeptide. The lipo-Nter was purified and
      formulated with protein or peptide vaccines to determine if lipo-Nter could be
      used as a novel adjuvant and could induce antitumor immunity in a cervical cancer
      model. Purified lipo-Nter activated the maturation of bone marrow-derived
      dendritic cells (BM-DCs), leading to the secretion of TNF-alpha through TLR2/6
      but not TLR1/2. A recombinant mutant HPV16 E7 (rE7m) protein was mixed with lipo
      Nter to immunize the mice; the anti-E7 antibody titers were increased, and the T
      helper cells were skewed toward the Th1 fate (increased IL-2 and decreased IL-5
      secretion). Single-dose injection of rE7m and lipo-Nter inhibited tumor growth,
      but the injection of rE7m alone did not. Accordingly, lipo-Nter also enhanced the
      antitumor immunity of the E7-derived peptide but not the synthetic lipopeptide
      (Pam3CSK4). We demonstrated that the lipo-Nter of a bacterial-derived recombinant
      lipoprotein is a novel adjuvant that could be used for the development of a new
      generation of vaccines.

PMID- 24738055
TI  - The design of a quantitative western blot experiment.
AB  - Western blotting is a technique that has been in practice for more than three
      decades that began as a means of detecting a protein target in a complex sample.
      Although there have been significant advances in both the imaging and reagent
      technologies to improve sensitivity, dynamic range of detection, and the
      applicability of multiplexed target detection, the basic technique has remained
      essentially unchanged. In the past, western blotting was used simply to detect a
      specific target protein in a complex mixture, but now journal editors and
      reviewers are requesting the quantitative interpretation of western blot data in
      terms of fold changes in protein expression between samples. The calculations are
      based on the differential densitometry of the associated chemiluminescent and/or
      fluorescent signals from the blots and this now requires a fundamental shift in
      the experimental methodology, acquisition, and interpretation of the data. We
      have recently published an updated approach to produce quantitative densitometric
      data from western blots (Taylor et al., 2013) and here we summarize the complete
      western blot workflow with a focus on sample preparation and data analysis for
      quantitative western blotting. 

PMID- 24738057
TI  - Experimental inoculation of BFDV-positive budgerigars (Melopsittacus undulatus)
      with two Mycobacterium avium subsp. avium isolates.
AB  - Beak and feather disease virus- (BFDV-) positive (naturally infected) but
      clinically healthy budgerigars (Melopsittacus undulatus) were inoculated with two
      isolates of Mycobacterium avium subsp. avium isolated from naturally infected
      golden pheasant (Chrysolophus pictus) and peafowl (Pavo cristatus). During a
      period of more than two months after inoculation, samples of cloacal and crop
      swabs, faeces, and blood were obtained for BFDV and Mycobacterium avium testing
      with PCR. Birds were euthanized nine weeks after inoculation. All infected
      budgerigars developed signs typical of mycobacteriosis, but more advanced
      clinical and pathological changes were visible in the group infected with the
      pheasant isolate. Only a few cloacal and crop swab samples were positive for
      Mycobacterium avium subsp. avium despite advanced pathological changes in the
      internal organs. In the groups infected with mycobacterium isolates the frequency
      of BFDV-positive samples was higher than in the control group. In the infected
      groups the frequency of BFDV was substantially higher in the cloacal swabs of
      birds inoculated with the pheasant isolate than in the peafowl-isolate-infected
      group. 

PMID- 24738056
TI  - Pushing CT and MR imaging to the molecular level for studying the "omics":
      current challenges and advancements.
AB  - During the past decade, medical imaging has made the transition from anatomical
      imaging to functional and even molecular imaging. Such transition provides a
      great opportunity to begin the integration of imaging data and various levels of
      biological data. In particular, the integration of imaging data and multiomics
      data such as genomics, metabolomics, proteomics, and pharmacogenomics may open
      new avenues for predictive, preventive, and personalized medicine. However, to
      promote imaging-omics integration, the practical challenge of imaging techniques
      should be addressed. In this paper, we describe key challenges in two imaging
      techniques: computed tomography (CT) and magnetic resonance imaging (MRI) and
      then review existing technological advancements. Despite the fact that CT and MRI
      have different principles of image formation, both imaging techniques can provide
      high-resolution anatomical images while playing a more and more important role in
      providing molecular information. Such imaging techniques that enable single
      modality to image both the detailed anatomy and function of tissues and organs of
      the body will be beneficial in the imaging-omics field. 

PMID- 24738058
TI  - Adult neurogenesis and glial oncogenesis: when the process fails.
AB  - Malignant brain tumors, including glioblastoma multiforme (GBM), are known for
      their high degree of invasiveness, aggressiveness, and lethality. These tumors
      are made up of heterogeneous cell populations and only a small part of these
      cells (known as cancer stem cells) is responsible for the initiation and
      recurrence of the tumor. The biology of cancer stem cells and their role in brain
      tumor growth and therapeutic resistance has been extensively investigated. Recent
      work suggests that glial tumors arise from neural stem cells that undergo a
      defective process of differentiation. The understanding of this process might
      permit the development of novel treatment strategies targeting cancer stem cells.
      In the present review, we address the mechanisms underlying glial tumor
      formation, paying special attention to cancer stem cells and the role of the
      microenvironment in preserving them and promoting tumor growth. Recent
      advancements in cancer stem cell biology, especially regarding tumor initiation
      and resistance to chemo- or radiotherapy, have led to the development of novel
      treatment strategies that focus on the niche of the stem cells that make up the
      tumor. Encouraging results from preclinical studies predict that these findings
      will be translated into the clinical field in the near future. 

PMID- 24738059
TI  - A cross-sectional study examining youth smoking rates and correlates in Tbilisi,
      Georgia.
AB  - Georgia has high smoking rates; however, little is known about the prevalence and
      correlates of youth smoking. We conducted a secondary data analysis of a 2010
      cross-sectional survey of 1,879 secondary and postsecondary school students aged
      15 to 24 years in Tbilisi, Georgia, examining substance use, perceived risk, and
      recreational activities in relation to lifetime and current (past 30 days)
      smoking. Lifetime and current smoking prevalence was 46.1% and 22.6%,
      respectively. In secondary schools, lifetime smoking correlates included being
      male, consuming alcohol, lifetime marijuana use, and lower perceived risk (P's <=
      .001). Correlates of current smoking among lifetime smokers included being male,
      consuming alcohol, lifetime marijuana use, lower perceived risk, less frequently
      exercise, and more often going out (P's < .05). In postsecondary schools,
      lifetime smoking correlates included being male, consuming alcohol, lifetime
      marijuana use, lower perceived risk, more often going out, and recreational
      internet use (P's < .0). Correlates of current smoking among lifetime smokers
      included being male (P's = .04), consuming alcohol, marijuana use, lower
      perceived risk, and more often going out (P's < .05). Tobacco control
      interventions might target these correlates to reduce smoking prevalence in
      Georgian youth. 

PMID- 24738060
TI  - The role of M1 and M2 macrophages in prostate cancer in relation to extracapsular
      tumor extension and biochemical recurrence after radical prostatectomy.
AB  - INTRODUCTION: The aim of our work was to investigate the causal connection
      between M1 and M2 macrophage phenotypes occurrence and prostate cancer, their
      correlation with tumor extension (ECE), and biochemical recurrence (BR). PATIENT
      AND METHODS: Clinical and pathological data were prospectively gathered from 93
      patients treated with radical prostatectomy. Correlations of commonly used
      variables were evaluated with uni- and multivariate analysis. The relationship
      between M1 and M2 occurrence and BR was also assessed with Kaplan-Meier survival
      analysis. RESULTS: Above all in 63.4% there was a M2 prevalence. M1 occurred more
      frequently in OC disease, while M2 was more represented in ECE. At univariate
      analysis biopsy and pathologic GS and M2 were statistically correlated with ECE.
      Only pathologic GS and M2 confirmed to be correlated with ECE. According to
      macrophage density BCR free survival curves presented a statistically significant
      difference. When we stratified our population for M1 and M2,we did not find any
      statistical difference among curves. At univariate analysis GS, pTNM, and
      positive margins resulted to be significant predictors of BCR, while M1 and M2
      did not achieve the statistical significance. At multivariate analysis, only GS
      and pathologic stage were independent predictors of BR. CONCLUSION: In our study
      patients with higher density of M count were associated with poor prognosis; M2
      phenotype was significantly associated with ECE.

PMID- 24738061
TI  - Cloning and expression of a cytosolic HSP90 gene in Chlorella vulgaris.
AB  - Heat shock protein 90 (HSP90), a highly conserved molecular chaperone, plays
      essential roles in folding, keeping structural integrity, and regulating the
      subset of cytosolic proteins. We cloned the cDNA of Chlorella vulgaris HSP90
      (named CvHSP90) by combining homology cloning with rapid amplification of cDNA
      ends (RACE). Sequence analysis indicated that CvHSP90 is a cytosolic member of
      the HSP90 family. Quantitative RT-PCR was applied to determine the expression
      level of messenger RNA (mRNA) in CvHSP90 under different stress conditions. C.
      vulgaris was kept in different temperatures (5-45  degrees C) for 1 h. The mRNA
      expression level of CvHSP90 increased with temperature from 5 to 10  degrees C,
      went further from 35 to 40  degrees C, and reached the maximum at 40  degrees C.
      On the other hand, for C. vulgaris kept at 35  degrees C for different durations,
      the mRNA expression level of CvHSP90 increased gradually and reached the peak at
      7 h and then declined progressively. In addition, the expression level of CvHSP90
      at 40 or 45 in salinity (0/00) was almost fourfold of that at 25 in salinity
      (0/00) for 2 h. Therefore, CvHSP90 may be a potential biomarker to monitor
      environment changes.

PMID- 24738062
TI  - TFIIB-related factor 2 is associated with poor prognosis of nonsmall cell lung
      cancer patients through promoting tumor epithelial-mesenchymal transition.
AB  - In this study, we found that increased BRF2 protein expression was prevalent in
      NSCLC. Overexpression of BRF2 correlated with abnormal expression of E-cadherin,
      N-cadherin, and snail. Additionally, expression of BRF2 was found to be an
      independent prognostic factor in NSCLC patients. Furthermore, we showed that
      targeted knockdown of BRF2 expression could inhibit the migratory and invasive
      abilities of NSCLC cells and induced loss of the epithelial-mesenchymal
      transition of NSCLC cells. These results suggested that BRF2 overexpression in
      tumor tissues is significantly associated with the poor prognosis of NSCLC
      patients through promoting epithelial-mesenchymal transition (EMT) program. 

PMID- 24738063
TI  - Recent progress in cryopreservation of bovine oocytes.
AB  - Principle of oocyte cryoinjury is first overviewed and then research history of
      cryopreservation using bovine oocytes is summarized for the last two decades with
      a few special references to recent progresses. Various types of cryodevices have
      been developed to accelerate the cooling rate and applied to the oocytes from
      large domestic species enriched with cytoplasmic lipid droplets. Two recent
      approaches include the qualitative improvement of IVM oocytes prior to the
      vitrification and the short-term recovery culture of vitrified-warmed oocytes
      prior to the subsequent IVF. Supplementation of L-carnitine to IVM medium of
      bovine oocytes has been reported to reduce the amount of cytoplasmic lipid
      droplets and improve the cryotolerance of the oocytes, but it is still
      controversial whether the positive effect of L-carnitine is reproducible.
      Incidence of multiple aster formation, a possible cause for low developmental
      potential of vitrified-warmed bovine oocytes, was inhibited by a short-term
      culture of the postwarm oocytes in the presence of Rho-associated coiled-coil
      kinase (ROCK) inhibitor. Use of an antioxidant alpha-tocopherol, instead of the
      ROCK inhibitor, also supported the revivability of the postwarm bovine oocytes.
      Further improvements of the vitrification procedure, combined with pre- and
      postvitrification chemical treatment, would overcome the high sensitivity of
      bovine oocytes to cryopreservation. 

PMID- 24738064
TI  - Biotechnology and green chemistry.

PMID- 24738065
TI  - Endothelial dysfunction in experimental models of arterial hypertension: cause or
      consequence?
AB  - Hypertension is a risk factor for other cardiovascular diseases and endothelial
      dysfunction was found in humans as well as in various commonly employed animal
      experimental models of arterial hypertension. Data from the literature indicate
      that, in general, endothelial dysfunction would not be the cause of experimental
      hypertension and may rather be secondary, that is, resulting from high blood
      pressure (BP). The initial mechanism of endothelial dysfunction itself may be
      associated with a lack of endothelium-derived relaxing factors (mainly nitric
      oxide) and/or accentuation of various endothelium-derived constricting factors.
      The involvement and role of endothelium-derived factors in the development of
      endothelial dysfunction in individual experimental models of hypertension may
      vary, depending on the triggering stimulus, strain, age, and vascular bed
      investigated. This brief review was focused on the participation of endothelial
      dysfunction, individual endothelium-derived factors, and their mechanisms of
      action in the development of high BP in the most frequently used rodent
      experimental models of arterial hypertension, including nitric oxide deficient
      models, spontaneous (pre)hypertension, stress-induced hypertension, and selected
      pharmacological and diet-induced models. 

PMID- 24738066
TI  - Quantitative proteomics analysis of altered protein expression in the placental
      villous tissue of early pregnancy loss using isobaric tandem mass tags.
AB  - Many pregnant women suffer miscarriages during early gestation, but the
      description of these early pregnancy losses (EPL) can be somewhat confusing
      because of the complexities of early development. Thus, the identification of
      proteins with different expression profiles related to early pregnancy loss is
      essential for understanding the comprehensive pathophysiological mechanism. In
      this study, we report a gel-free tandem mass tags- (TMT-) labeling based
      proteomic analysis of five placental villous tissues from patients with early
      pregnancy loss and five from normal pregnant women. The application of this
      method resulted in the identification of 3423 proteins and 19647 peptides among
      the patient group and the matched normal control group. Qualitative and
      quantitative proteomic analysis revealed 51 proteins to be differentially
      abundant between the two groups (>= 1.2-fold, Student's t-test, P < 0.05). To
      obtain an overview of the biological functions of the proteins whose expression
      levels altered significantly in EPL group, gene ontology analysis was performed.
      We also investigated the twelve proteins with a difference over 1.5-fold using
      pathways analysis. Our results demonstrate that the gel-free TMT-based proteomic
      approach allows the quantification of differences in protein expression levels,
      which is useful for obtaining molecular insights into early pregnancy loss.

PMID- 24738067
TI  - Exact and heuristic methods for network completion for time-varying genetic
      networks.
AB  - Robustness in biological networks can be regarded as an important feature of
      living systems. A system maintains its functions against internal and external
      perturbations, leading to topological changes in the network with varying delays.
      To understand the flexibility of biological networks, we propose a novel approach
      to analyze time-dependent networks, based on the framework of network completion,
      which aims to make the minimum amount of modifications to a given network so that
      the resulting network is most consistent with the observed data. We have
      developed a novel network completion method for time-varying networks by
      extending our previous method for the completion of stationary networks. In
      particular, we introduce a double dynamic programming technique to identify
      change time points and required modifications. Although this extended method
      allows us to guarantee the optimality of the solution, this method has relatively
      low computational efficiency. In order to resolve this difficulty, we developed a
      heuristic method for speeding up the calculation of minimum least squares errors.
      We demonstrate the effectiveness of our proposed methods through computational
      experiments using synthetic data and real microarray gene expression data. The
      results indicate that our methods exhibit good performance in terms of completing
      and inferring gene association networks with time-varying structures. 

PMID- 24738068
TI  - A systematic follow-up of Mycobacterium tuberculosis drug-resistance and
      associated genotypic lineages in the French Departments of the Americas over a
      seventeen-year period.
AB  - THE population of the French Departments of the Americas (FDA) is highly
      influenced by the intense migratory flows with mainland france and surrounding
      countries of the Caribbean and Latin America, some of which have high incidence
      rates of tuberculosis (Haiti: 230/100,000; Guyana: 111/100,000; and Suriname:
      145/100,000) and drug resistance. Since the development of drug resistance to
      conventional antituberculous drugs has a major impact on the treatment success of
      tuberculosis, we therefore decided to review carefully Mycobacterium tuberculosis
      drug resistance and associated genotypic lineages in the FDA over a seventeen
      year period (January 1995-December 2011). A total of 1239 cases were studied,
      including 153 drug-resistant and 26 multidrug-resistant- (MDR-) TB cases,
      representing 12.3% and 2.1% of the TB cases in our study setting. A significantly
      higher proportion of M. tuberculosis isolates among relapse cases showed drug
      resistance to isoniazid (22.5%, P = 0.002), rifampicin (20.0%, P < 0.001), or
      both (MDR-TB, 17.5%; P < 0.001). Determination of spoligotyping based
      phylogenetic clades showed that among the five major lineages observed--T family
      (30.1%); Latin-American and Mediterranean (LAM, 23.7%); Haarlem (H, 22.2%); East
      African Indian (EAI, 7.2%); and X family (6.5%)--two lineages, X and LAM, were
      overrepresented in drug-resistant and MDR-TB cases, respectively. Finally, 19
      predominant spoligotypes were identified for the 1239 isolates of M. tuberculosis
      in our study among which 4 were significantly associated with drug resistance
      corresponding to SIT20/LAM1, SIT64/LAM6, SIT45/H1, and SIT46/undefined lineage.

PMID- 24738069
TI  - COgnitive-pulmonary disease.
AB  - Over the past few decades, chronic obstructive lung disease (COPD) has been
      considered a disease of the lungs, often caused by smoking. Nowadays, COPD is
      regarded as a systemic disease. Both physical effects and effects on brains,
      including impaired psychological and cognitive functioning, have been
      demonstrated. Patients with COPD may have cognitive impairment, either globally
      or in single cognitive domains, such as information processing, attention and
      concentration, memory, executive functioning, and self-control. Possible causes
      are hypoxemia, hypercapnia, exacerbations, and decreased physical activity.
      Cognitive impairment in these patients may be related to structural brain
      abnormalities, such as gray-matter pathologic changes and the loss of white
      matter integrity which can be induced by smoking. Cognitive impairment can have a
      negative impact on health and daily life and may be associated with widespread
      consequences for disease management programs. It is important to assess cognitive
      functioning in patients with COPD in order to optimize patient-oriented treatment
      and to reduce personal discomfort, hospital admissions, and mortality. This paper
      will summarize the current knowledge about cognitive impairment as extrapulmonary
      feature of COPD. Hereby, the impact of smoking on cognitive functioning and the
      impact of cognitive impairment on smoking behaviour will be examined. 

PMID- 24738071
TI  - Comment on "Effectiveness of naltrexone in the prevention of delayed respiratory
      arrest in opioid-naive methadone-intoxicated patients".

PMID- 24738070
TI  - Intracerebroventricular administration of nerve growth factor induces gliogenesis
      in sensory ganglia, dorsal root, and within the dorsal root entry zone.
AB  - Previous studies indicated that intracerebroventricular administration of nerve
      growth factor (NGF) leads to massive Schwann cell hyperplasia surrounding the
      medulla oblongata and spinal cord. This study was designed to characterize the
      proliferation of peripheral glial cells, that is, Schwann and satellite cells, in
      the trigeminal ganglia and dorsal root ganglia (DRG) of adult rats during two
      weeks of NGF infusion using bromodeoxyuridine (BrdU) to label dividing cells. The
      trigeminal ganglia as well as the cervical and lumbar DRG were analyzed. Along
      the entire neuraxis a small number of dividing cells were observed within these
      regions under physiological condition. NGF infusion has dramatically increased
      the generation of new cells in the neuronal soma and axonal compartments of
      sensory ganglia and along the dorsal root and the dorsal root entry zone.
      Quantification of BrdU positive cells within sensory ganglia revealed a 2.3- to 3
      fold increase in glial cells compared to controls with a similar response to NGF
      for the different peripheral ganglia examined. Immunofluorescent labeling with
      S100beta revealed that Schwann and satellite cells underwent mitosis after NGF
      administration. These data indicate that intracerebroventricular NGF infusion
      significantly induces gliogenesis in trigeminal ganglia and the spinal sensory
      ganglia and along the dorsal root entry zone as well as the dorsal root.

PMID- 24738072
TI  - Propolis modulates fibronectin expression in the matrix of thermal injury.
AB  - The aim of the study was to assess the propolis effect on fibronectin metabolism
      in the course of burn wounds healing process. A model of burn wound healing of
      pig skin was applied. The amount of the released glycoprotein was assessed by a
      surface plasmon resonance. The profile of extracted fibronectin components was
      also assessed by an electrophoresis in polyacrylamide gel, with a subsequent
      immunodetection by Western Blotting. Propolis burn treatment decreased the
      release of fibronectin components from healing wounds in relation to damages
      treated with silver sulfadiazine. The main reason of decreased extraction of
      fibronectin components from wounds treated with propolis was a substantial
      decrease of degradation product release of the mentioned glycoprotein, which was
      observed particularly from the 3rd to 5th day of the repair. Wounds treatment
      with propolis demonstrated, especially in relation to damages treated with silver
      sulfadiazine, the decreased release of synthesized fibronectin molecules. The
      obtained results suggest that propolis modifies fibronectin metabolism in the
      course of wound healing process. The influence of propolis is reflected in
      prevention of fibronectin biosynthesis as well as its degradation in the wound
      area. The above-mentioned metabolic changes may decrease the risk of
      complications in the repair wounds process. 

PMID- 24738073
TI  - High versus moderate intensity running exercise to impact cardiometabolic risk
      factors: the randomized controlled RUSH-study.
AB  - Aerobic exercise positively impacts cardiometabolic risk factors and diseases;
      however, the most effective exercise training strategies have yet to be
      identified. To determine the effect of high intensity (interval) training
      (HI(I)T) versus moderate intensity continuous exercise (MICE) training on
      cardiometabolic risk factors and cardiorespiratory fitness we conducted a 16-week
      crossover RCT with partial blinding. Eighty-one healthy untrained middle-aged
      males were randomly assigned to two study arms: (1) a HI(I)T-group and (2) a
      sedentary control/MICE-group that started their MICE protocol after their control
      status. HI(I)T focused on interval training (90 sec to 12 min >85-97.5% HRmax)
      intermitted by active recovery (1-3 min at 65-70% HRmax), while MICE consisted of
      continuous running at 65-75% HRmax. Both exercise groups progressively performed
      2-4 running sessions/week of 35 to 90 min/session; however, protocols were
      adjusted to attain similar total work (i.e., isocaloric conditions). With respect
      to cardiometabolic risk factors and cardiorespiratory fitness both exercise
      groups demonstrated similar significant positive effects on MetS-Z-Score (HI(I)T:
      -2.06 +/- 1.31, P = .001 versus MICE: -1.60 +/- 1.77, P = .001) and (relative)
      VO2max (HI(I)T: 15.6 +/- 9.3%, P = .001 versus MICE: 10.6 +/- 9.6%, P = .001)
      compared with the sedentary control group. In conclusion, both exercise programs
      were comparably effective for improving cardiometabolic indices and
      cardiorespiratory fitness in untrained middle-aged males.

PMID- 24738074
TI  - Role of plasma membrane caveolae/lipid rafts in VEGF-induced redox signaling in
      human leukemia cells.
AB  - Caveolae/lipid rafts are membrane-rich cholesterol domains endowed with several
      functions in signal transduction and caveolin-1 (Cav-1) has been reported to be
      implicated in regulating multiple cancer-associated processes, ranging from tumor
      growth to multidrug resistance and angiogenesis. Vascular endothelial growth
      factor receptor-2 (VEGFR-2) and Cav-1 are frequently colocalized, suggesting an
      important role played by this interaction on cancer cell survival and
      proliferation. Thus, our attention was directed to a leukemia cell line (B1647)
      that constitutively produces VEGF and expresses the tyrosine-kinase receptor
      VEGFR-2. We investigated the presence of VEGFR-2 in caveolae/lipid rafts,
      focusing on the correlation between reactive oxygen species (ROS) production and
      glucose transport modulation induced by VEGF, peculiar features of tumor
      proliferation. In order to better understand the involvement of VEGF/VEGFR-2 in
      the redox signal transduction, we evaluated the effect of different compounds
      able to inhibit VEGF interaction with its receptor by different mechanisms,
      corroborating the obtained results by immunoprecipitation and fluorescence
      techniques. Results here reported showed that, in B1647 leukemia cells, VEGFR-2
      is present in caveolae through association with Cav-1, demonstrating that
      caveolae/lipid rafts act as platforms for negative modulation of VEGF redox
      signal transduction cascades leading to glucose uptake and cell proliferation,
      suggesting therefore novel potential targets. 

PMID- 24738075
TI  - A diverse stochastic search algorithm for combination therapeutics.
AB  - BACKGROUND: Design of drug combination cocktails to maximize sensitivity for
      individual patients presents a challenge in terms of minimizing the number of
      experiments to attain the desired objective. The enormous number of possible drug
      combinations constrains exhaustive experimentation approaches, and personal
      variations in genetic diseases restrict the use of prior knowledge in
      optimization. RESULTS: We present a stochastic search algorithm that consisted of
      a parallel experimentation phase followed by a combination of focused and
      diversified sequential search. We evaluated our approach on seven synthetic
      examples; four of them were evaluated twice with different parameters, and two
      biological examples of bacterial and lung cancer cell inhibition response to
      combination drugs. The performance of our approach as compared to recently
      proposed adaptive reference update approach was superior for all the examples
      considered, achieving an average of 45% reduction in the number of experimental
      iterations. CONCLUSIONS: As the results illustrate, the proposed diverse
      stochastic search algorithm can produce optimized combinations in relatively
      smaller number of iterative steps. This approach can be combined with available
      knowledge on the genetic makeup of the patient to design optimal selection of
      drug cocktails.

PMID- 24738077
TI  - Abnormal early gamma responses to emotional faces differentiate unipolar from
      bipolar disorder patients.
AB  - This study investigates the cortical abnormalities of early emotion perception in
      patients with major depressive disorder (MDD) and bipolar disorder (BD) using
      gamma oscillations. Twenty-three MDD patients, twenty-five BD patients, and
      twenty-four normal controls were enrolled and their event-related
      magnetoencephalographic responses were recorded during implicit emotional tasks.
      Our results demonstrated abnormal gamma activity within 100 ms in the emotion
      related regions (amygdala, orbitofrontal (OFC) cortex, anterior insula (AI), and
      superior temporal pole) in the MDD patients, suggesting that these patients may
      have dysfunctions or negativity biases in perceptual binding of emotional
      features at very early stage. Decreased left superior medial frontal cortex
      (smFC) responses to happy faces in the MDD patients were correlated with their
      serious level of depression symptoms, indicating that decreased smFC activity
      perhaps underlies irregular positive emotion processing in depressed patients. In
      the BD patients, we showed abnormal activation in visual regions (inferior/middle
      occipital and middle temporal cortices) which responded to emotional faces within
      100 ms, supporting that the BD patients may hyperactively respond to emotional
      features in perceptual binding. The discriminant function of gamma activation in
      the left smFC, right medial OFC, right AI/inferior OFC, and the right precentral
      cortex accurately classified 89.6% of patients as unipolar/bipolar disorders.

PMID- 24738078
TI  - Disturbances of sperm maturation and minipuberty: is there a connection?
AB  - Male reproductive function in the general population raises an increased
      attention due to reports indicating declining sperm counts, increased occurrence
      of testicular cancer, cryptorchidism, and hypospadias. It is also hypothesized
      that prolonged exposure of the developing male, during both fetal and postnatal
      life, to exogenous estrogens could reduce Sertoli cell number and thus reduce
      sperm output (and sperm counts) in adult life. Fact is that infertility, which is
      defined as the inability to conceive after 1 year of unprotected intercourse, has
      a global prevalence of 9%. A male contributory factor is involved in
      approximately half of these cases, but most of the causes of reduced semen
      quality and other disturbances of male reproductive function are unknown. In the
      most affected men (azoospermic men) 15-20% had a prior history of cryptorchidism.
      The association between the cryptorchidism and infertility is one of the most
      studied potential causes of infertility. There are numerous studies that
      accentuate the importance of minipuberty for future fertility. Is it possible
      that a normal minipuberty ensures normal fertility despite malpositioned testes?
      And to move away from cryptorchidism, could impaired minipuberty be responsible
      for fertility problems in men who were born with both testes in their scrotal
      sacs? 

PMID- 24738079
TI  - Reliability of a simple physical therapist screening tool to assess errors during
      resistance exercises for musculoskeletal pain.
AB  - The main objective was to investigate the intra- and intertester reliability of a
      simple screening tool assessing errors in exercise execution by visual
      observation. 38 participants with no previous resistance exercise experience
      practiced for two weeks four typical upper limb exercises using elastic tubing.
      At 2-week follow-up, the participants were invited for a test-retest assessment
      on errors in technical execution. The assessment was based on ordinal deviation
      of joint position from neutral of the shoulder, elbow, and wrist in a single
      plane by visual observation. Moderate intratester reliability weighted kappa
      (wKappa) score ranging from 0.50 (0.21-0.71) to 0.57 (0.24-0.82) for observer 1
      and a fair to moderate intratester reliability wKappa score ranging from 0.27
      (0.09-0.43) to 0.52 (0.15-0.86) for observer 2 across the four exercises was
      observed. For intertester reliability moderate to substantial mean wKappa scores
      were found between the two observers, slightly improving from round one to round
      two ranging from 0.40 (0.20-0.59) to 0.68 (0.45-0.91) in round one to 0.52 (0.20
      0.80) to 0.69 (0.39-0.86) in round two. The exercise error assessment
      demonstrated fair to substantial intratester and intertester reliability, which
      is congruent with previously published studies. Hence the simplicity of defining
      a neutral joint position for each of the involved joints in the exercise and
      categorizing the deviation in "some deviation" and "substantial deviation" to
      either side in a single plane is a viable and inexpensive solution when assessing
      for errors during exercise. 

PMID- 24738080
TI  - Automatic detection and quantification of acute cerebral infarct by fuzzy
      clustering and histographic characterization on diffusion weighted MR imaging and
      apparent diffusion coefficient map.
AB  - Determination of the volumes of acute cerebral infarct in the magnetic resonance
      imaging harbors prognostic values. However, semiautomatic method of segmentation
      is time-consuming and with high interrater variability. Using diffusion weighted
      imaging and apparent diffusion coefficient map from patients with acute
      infarction in 10 days, we aimed to develop a fully automatic algorithm to measure
      infarct volume. It includes an unsupervised classification with fuzzy C-means
      clustering determination of the histographic distribution, defining self-adjusted
      intensity thresholds. The proposed method attained high agreement with the
      semiautomatic method, with similarity index 89.9 +/- 6.5%, in detecting cerebral
      infarct lesions from 22 acute stroke patients. We demonstrated the accuracy of
      the proposed computer-assisted prompt segmentation method, which appeared
      promising to replace the laborious, time-consuming, and operator-dependent
      semiautomatic segmentation. 

PMID- 24738076
TI  - Low temperature plasma: a novel focal therapy for localized prostate cancer?
AB  - Despite considerable advances in recent years for the focal treatment of
      localized prostate cancer, high recurrence rates and detrimental side effects are
      still a cause for concern. In this review, we compare current focal therapies to
      a potentially novel approach for the treatment of early onset prostate cancer:
      low temperature plasma. The rapidly evolving plasma technology has the potential
      to deliver a wide range of promising medical applications via the delivery of
      plasma-induced reactive oxygen and nitrogen species. Studies assessing the effect
      of low temperature plasma on cell lines and xenografts have demonstrated DNA
      damage leading to apoptosis and reduction in cell viability. However, there have
      been no studies on prostate cancer, which is an obvious candidate for this novel
      therapy. We present here the potential of low temperature plasma as a focal
      therapy for prostate cancer. 

PMID- 24738081
TI  - Liquiritigenin induces tumor cell death through mitogen-activated protein kinase-
      (MPAKs-) mediated pathway in hepatocellular carcinoma cells.
AB  - Liquiritigenin (LQ), separated from Glycyrrhiza radix, possesses anti
      inflammatory, antihyperlipidemic, and antiallergic effects. Our present study
      aims to investigate the antihepatocellular carcinoma effects of LQ both in cell
      and animal models. LQ strikingly reduced cell viability, enhanced apoptotic rate,
      induced lactate dehydrogenase over-release, and increased intracellular reactive
      oxygen species (ROS) level and caspase 3 activity in both PLC/PRL/5 and HepG2
      cells. The expression of cleaved PARP, the hall-marker of apoptosis, was enhanced
      by LQ. LQ treatment resulted in a reduction of the expressions of B-cell lymphoma
      2 (Bcl-2) and B-cell lymphoma-extra large (Bcl-xL), and an increase of the
      phosphorylation of c-Jun N-terminal kinases (JNK) and P38. LQ-mediated cell
      viability reduction, mitochondrial dysfunction, apoptosis related protein
      abnormal expressions, and JNK and P38 activation were partially abolished by N
      Acetyl-L-cysteine (a ROS inhibitor) pretreatment. Moreover, LQ suppressed the
      activation of extracellular signaling-regulated kinase (ERKs) and reduced the
      translocation of phosphor-ERKs from cytoplasm to nucleus. This antitumor activity
      was further confirmed in PLC/PRL/5-xenografted mice model. All these data
      indicate that the antihepatocellular carcinoma effects of LQ are related to its
      modulation of the activations of mitogen-activated protein kinase (MAPKs). The
      study provides experimental evidence supporting LQ as a potential therapeutic
      agent for hepatocellular carcinoma treatment. 

PMID- 24738082
TI  - Gender Differences in Trauma and Posttraumatic Stress Symptoms among Displaced
      Zimbabweans in South Africa.
AB  - BACKGROUND: Over the years, more than 3.4 million Zimbabweans (a quarter of the
      country's population) have fled the country to other countries with South Africa
      as the main popular destination. In South Africa, they become a vulnerable group
      with the plausibility of suffering trauma and PTSS or PTSD due to xenophobic
      attacks and resentment. How males and females are impacted is undocumented in
      psychological literature, particularly with regards to Africa. In addition,
      global research on gender differences, trauma and PTSS/PTSD are inconclusive.
      This paper explores gender differences in PTSS among displaced Zimbabweans in
      South Africa. A poor mental health status, pre and post-migration traumas of men
      and women were hypothesized to have a relationship with PTSS for women, but not
      to the same extent for men. METHOD: Through a guided purposive convenient
      sampling, in-depth interviews using questionnaires, data were obtained from a
      sample of 125 displaced and homeless Zimbabwean refugees in Polokwane, Limpopo
      Province, South Africa. Participants were assessed on demographic variables, pre-
      and post-migration difficulties checklists, mental health using the General
      Health Questionnaire (GHQ-28) and the PTSD Checklist (Civilian Version (PCL).
      RESULT: The hypothesis of a gender difference in the predictability of PTSD was
      tested in structural equation models. For men none of the three paths (pre
      migration stress, post-migration stress, and poor mental health) on PTSD is
      significant, whereas for women both the path from poor mental health onto PTSD
      (beta=.36, p=.013) are significant, but the size of the gender differences was
      modest. However, effect sizes are always larger for women than they are for men.
      CONCLUSION: The findings help closing the gap in PTSS/PTSD research for Africans
      and suggest that indeed likely gender differences in the prediction of PTSS,
      suggested in the literature, needs further attention.

PMID- 24738083
TI  - Evaluation of Isfahan's Dental Students' Awareness about Preventive Dentistry.
AB  - STATEMENT OF PROBLEM: The modern dentistry approach is moving toward preventive
      dentistry, an approach that has decreased the prevalence of caries within the
      past decades. Since some reports imply that dentists are not knowledgeable enough
      in this issue. PURPOSE: This study aimed to evaluate the attitude and awareness
      of future dental graduates toward preventive dentistry regarding gender and
      educational characteristics. MATERIALS AND METHOD: This cross-sectional study was
      performed on one hundred and forty questionnaires which were distributed among
      dental students of Isfahan province, Azad university of Khorasgan, Iran. Data
      regarding the level of awareness of dental students about preventive dentistry
      were recorded and analyzed by using the mean and standard deviations on scores as
      appropriated. RESULTS: Majority of dental students were aware about the role of
      sugar in caries process, while only a minority were aware about the role of
      fluoridated toothpaste and brushing method in caries prevention. Most of the
      students (82.1%) were among the group with medium level of awareness. Compared
      with their female counterparts, male students had more knowledge about fluoride
      efficacy and general hygiene role in caries process. CONCLUSION: Dental students
      of  the Isfahan State University and Azad University of Khorasgan had acceptable
      levels of awareness about the role of sugar and fluoridated water in caries
      process, but were not aware enough about the role of fluoridated toothpaste in
      preventing dental caries.

PMID- 24738084
TI  - Influence of different bonding agents and composite resins on fracture resistance
      of reattached incisal tooth fragment.
AB  - STATEMENT OF PROBLEM: Reattachment of the fractured tooth fragment should be
      considered as a conservative treatment and valid alternative to a composite
      restoration. PURPOSE: This in vitro study was to evaluate the influence of
      different adhesives and composite resins on fracture resistance of dental
      fragment reattached to the sectioned incisal edges. MATERIALS AND METHOD: 120
      sound human maxillary central incisors were selected under standard conditions
      and randomly divided into 3 groups, 12 sound teeth were used as a control group
      and the remaining teeth were assigned to 3 groups (n=36) and each group into
      three subgroups (n=12). The incisal third of the samples was sectioned using a
      diamond disk and the respective fragments were then reattached utilizing
      different intermediate restorative materials, namely: i) adhesive materials alone
      (OptiBond S or OptiBond XTR or OptiBond All-in-One; ii) Premise flowable
      composite and iii) Point 4 composite in the one of the mentioned adhesive
      interface. After storage for two weeks at 37 degrees C and 100% humidity and then
      thermocycling; shear bond strength (SBS) was recorded in kilogram force (kgf) by
      applying a load in the middle incisal third with a Zwick Universal Testing
      Machine at a cross-head speed of 1 mm/min. Data was analyzed with one-way ANOVA
      and Tukey HSD (p< 0.05). RESULTS: The control group had a significantly higher
      SBS than other groups (p= 0.001); the highest SBS values were obtained using the
      Premise flowable composite and OptiBond S adhesive (112.44+/-30.46 MPa); and the
      lowest with OptiBond All-in-One alone (33.97+/- 15.63 MPa). CONCLUSION: Although,
      none of the tested materials provided fracture resistance similar to that found
      with the intact maxillary central incisors; utilizing the Premise flowable
      composite and OptiBond S adhesive improved the SBS of the reattached fragment
      than other materials.

PMID- 24738085
TI  - A retrospective analysis of maxillofacial trauma in shiraz, iran: a 6-year- study
      of 768 patients (2004-2010).
AB  - STATEMENT OF PROBLEM: Information about the etiology and incidence of
      maxillofacial trauma is important for prevention and appropriate treatments of
      such injuries. PURPOSE: The purpose of this retrospective study was to conduct an
      analysis of maxillofacial injuries transferred and/or referred to the department
      of maxillofacial Surgery at Chamran emergency hospital, Shiraz, over a 6-year
      period with special reference to age, gender, occupation, date, type, site,
      etiology and clinical management. MATERIALS AND METHOD: The data for this study
      were collected and reviewed retrospectively from the records and radiographs of
      768 patients who were treated for maxillofacial trauma in the department of
      maxillofacial surgery at the Shiraz Chamran Emergency Hospital, Iran, between
      2004 and 2010. RESULTS: A total of 730 of the subjects were the patients with
      fractures of the facial skeleton. The mean age was 26.6+/- 12.6 years, ranging
      from 2 to 81 years. Traffic accident was the most frequent etiological factor of
      maxillofacial fractures irrespective of gender (69.9% for men and 54.2% for
      women), whereas the second most frequent cause of injuries was falling down (9.8%
      for men and 21.5% for women) .The other etiologies were assaults (5.2%), sport
      related injuries (1.3%) and firearm injuries (1%). Regarding the head injuries in
      patients with maxillofacial fractures, brain contusion was seen in 227(29.6%)
      patients and 13.5% of patients had lacerations in the facial soft tissue. The
      monthly distribution peaked in October, with 81 cases (10.5%), which would be for
      the reason that schools open in this month. The next highest incidence was in
      December, with 80 cases (10.4%), probably because of the changing weather's
      effect on road traffic. CONCLUSION: Isolated mandibular fracture due to the road
      traffic accident was the most common type of maxillofacial injuries in the city
      of Shiraz.

PMID- 24738086
TI  - An In vitro Evaluation of the Effect of Four Dentin Bonding System on the Bond
      Strength between Quartz Fiber Post and Composite Core.
AB  - STATEMENT OF PROBLEM: A strong bond of fiber post to resin core, as well as to
      dentin would critically ensure the durability of restorations in endodontically
      treated teeth. PURPOSE: The purpose of this study was to evaluate the effect of
      etch-and-rinse dentin bonding systems on the bond strength between resin core and
      fiber post after application of 24% hydrogen peroxide.  MATERIALS AND METHOD: 24
      fiber posts (RTD; St. Egeven, France) were treated with 24% hydrogen peroxide for
      10 minutes. They were randomly divided into 4 groups (n=6) based on the bonding
      agent used: Group P: Prime&Bond, Group O: One Step, Group S: Single Bond and
      Group E: Excite. Each group was prepared according to the manufacturer's
      instructions. For all posts, a flowable composite core (AEliteFlo; Bisco, USA)
      was built-up over the bonded area. Each specimen was sectioned to produce 2
      sticks, 1mm in thickness and underwent microtensile bond strength (uTBS). Data
      were analyzed using one-way ANOVA at the 0.05 level. The fractured surfaces of
      all sticks were evaluated by stereomicroscope (* 20). Scanning electron
      microscopy(SEM) assessment of two sticks from each group was performed to
      evaluate the surface morphology. RESULTS: The means and SDs of uTBS were: Group
      P: 10.95+/-1.74; Group S: 10.25+/-2.39; Group E: 9.52+/-2.07; and Group O: 9.12+/
      1.34. There was no statistically significant difference in bond strength means
      between the groups tested (p> 0.05).   CONCLUSION: The results of this study
      indicated the bonding agents used had no significant influence on the bond
      strength of fiber post to composite core.

PMID- 24738087
TI  - An In vitro Comparison of Furcal Perforation Repaired with Pro-root MTA and New
      Endodontic Cement in Primary Molar Teeth- A Microleakage Study.
AB  - STATEMENT OF PROBLEM: One of the most challenging procedural accidents during
      pulpotomy of primary molars is furcal perforation. To prevent bacterial invasion,
      the perforation site should be sealed as soon as possible. PURPOSE: The aim of
      the current study is to investigate the ability of the pro-root MTA and new
      endodontic cement (NEC) in repairing the furcation perforations of primary molar
      teeth. MATERIALS AND METHOD: In this in vitro study, 42 extracted primary molars
      were selected. Their roots were sectioned horizontally and standard access cavity
      was prepared. The orifices and the root apices were sealed with two layers of
      resin composite.The samples were randomly assigned into 2 groups. 6 teeth were
      considered as the positive and the negative controls. In the experimental groups;
      perforation was made. In group 1 and 2, perforation site received pro-root MTA
      and NEC respectively. The teeth were covered by two layers of nail polish except
      for the external surface of the perforation site. The negative control group
      received no repairing material. All teeth were mounted and sterilized for 24
      hours. Lower chambers were filled with sterilized Muller Hinton broth. Bacterial
      suspension of Enterococcus faecalis in 0.5 McFarland was prepared. The repaired
      site was then exposed to the bacterial suspension of Enterococcus faecalis every
      3 days. All samples were inserted in an incubator at 37(o)C and 100% humidity.
      The turbidity of the samples was detected for a period of 30 days. Data were
      analyzed by Chi- square test. RESULTS: 44% of samples in Pro- root group, 50% of
      the samples in the NEC group showed contaminations during 30 days. There was no
      significant difference between these two groups (p= 0.799). CONCLUSION: With
      limitations of this study, Pro- root MTA and NEC showed similar capability in
      sealing the furcal perforations of the primary molars.

PMID- 24738088
TI  - Dental Erosion in Patients with Gastroesophageal Reflux Disease (GERD) in a
      Sample of Patients Referred to the Motahari Clinic, Shiraz, Iran.
AB  - STATEMENT OF PROBLEM: Systematic reviews of the literature show that the dental
      erosion is associated with the gastroesophageal reflux disease (GERD).The
      prevalence of the problem may not be exclusively similar in different countries.
      PURPOSE: The purpose of this study was to investigate the association of gastro
      esophageal reflux disease (GERD) with dental erosion in a sample of Iranian
      population regarding the standing difference in the Iranian oral hygiene and
      diet. Material s and Method: 140 patients with the average age of 30 to 50 years
      old comprised the study group. The participants were already eligible for the
      endoscopic examination, diagnosed by their gastroenterologist. All patients
      completed a detailed questionnaire regarding the medical and dental situations.
      After completing the questionnaire and before endoscopy, dental examination was
      performed by two blinded dentists.The endoscopy was then performed by a
      gastroenterologist and the patients were divided into three groups of healthy,
      suspected to GERD, and positive GERD. Data were collected and analyzed by Chi-
      Square test. The cross tabulation test was performed to compare the qualitative
      variants and discover the correlations. The statistical significance was adopted
      as: p < 0.05. RESULTS: The prevalence of dental erosion in GERD patients (22.6%)
      was found to be higher than the suspected (5.3%) and the healthy (7%)
      individuals. CONCLUSION: This study declared the GERD patients are at higher risk
      of developing dental erosion compared to the healthy individuals in a sample of
      Iranian population.

PMID- 24738089
TI  - Comparison of the antibacterial effect of sodium hypochlorite and aloe vera
      solutions as root canal irrigants in human extracted teeth contaminated with
      enterococcus faecalis.
AB  - STATEMENT OF PROBLEM: The main purpose of a root canal treatment is to eliminate
      the bacteria and their products from the pulp space. Sodium hypochlorite has
      excellent antibacterial properties, but also some negative features. PURPOSE: The
      aim of the present study is to compare the antimicrobial effect of Aloe Vera
      solution with sodium hypochlorite on E.faecalis in the root canals of human
      extracted teeth. MATERIALS AND METHOD: Sixty human extracted single rooted teeth
      were selected for this in vitro study. The teeth recruited in this study had no
      cracks, internal resorption, external resorption and calcification. Enterococcus
      faecalis was injected in the root canals of all teeth. The teeth were then
      divided into three groups randomly. Each group consisted of 20 teeth that were
      all rinsed with one of the following solutions: sodium hypochlorite 2.5%, Aloe
      vera and normal saline. Subsequent to rinsing, root canals of all teeth were
      sampled. The samples were cultured and growth of the bacteria was assessed after
      48 hours. The number of colonies of the bacteria was then counted. RESULTS: The
      difference between the inhibitory effect of Aloe vera and normal saline on
      E.faecalis was not significant according to independent t-test (p= 0.966). The
      inhibitory effect of sodium hypochlorite on E.faecalis was much greater than that
      of Aloe vera and normal saline (p< 0.001). CONCLUSION: Aloe vera solution is not
      recommended as a root canal irrigator, but future studies are suggested to
      investigate the antibacterial effect of Aloe vera with longer duration of
      exposure and as an intra canal medicament.

PMID- 24738090
TI  - Direct esthetic rehabilitation of teeth with severe fluorosis: a case report.
AB  - This article describes an esthetic rehabilitation of a case of severe fluorosis
      associated with tooth mobility and gingival recession. Direct composite technique
      was applied to improve the color, shape and alignment of the teeth using direct
      composite veneering and replacement of the missing tooth by fiber-reinforced
      composite bridge. One year follow up have displayed acceptable outcomes and
      esthetic appearance. 

PMID- 24738091
TI  - Counterphobia and poor sun protection practices in first-degree relatives of
      melanoma patients.

PMID- 24738092
TI  - New HIPAA requirements.

PMID- 24738093
TI  - What does ICD-10 mean for dermatologists?

PMID- 24738094
TI  - Consensus recommendations from the American Acne & Rosacea Society on the
      management of rosacea, part 5: a guide on the management of rosacea.
AB  - The last article in this 5-part series provides a final overview of consensus
      recommendations from the American Acne & Rosacea Society (AARS) on the management
      of the common presentations of cutaneous rosacea. Optimal management of rosacea
      requires careful assessment of the patient's clinical features with integration
      of therapies that adequately treat the presenting signs and symptoms. The
      treatment consensus recommendations from the AARS are based on 2 major common
      clinical presentations of rosacea: (1) centrofacial erythema with papulopustular
      lesions, and (2) centrofacial erythema without papulopustular lesions. The
      recommendations provided here serve to guide clinicians in their clinical
      practice.

PMID- 24738095
TI  - Cutaneous squamous cell carcinoma with perineural invasion: a case report and
      review of the literature.
AB  - Perineural invasion (PNI) is an uncommon manifestation of cutaneous squamous cell
      carcinoma (SCC). We report a case of recurrent cutaneous SCC with PNI diagnosed
      both clinically and histologically. We also provide a review the literature.
      Clinicians should be aware of this uncommon finding, as PNI has been associated
      with increased local recurrence, local and distant metastasis, and poor
      prognosis. Patients with clinical findings associated with perineural involvement
      have a poorer prognosis than those incidentally discovered on histologic
      examination, which emphasizes the importance of a thorough history and neurologic
      examination in patients with cutaneous SCC to identify those who will require
      more aggressive therapy.

PMID- 24738096
TI  - Localized diffuse melanosis associated with melanoma successfully treated with
      imiquimod cream 5%: a case report and review of the literature.
AB  - Diffuse melanosis associated with melanoma is a rare condition characterized by
      rapidly acquired skin pigmentation that usually occurs in the setting of advanced
      metastatic melanoma. We report a case of localized diffuse melanosis associated
      with melanoma on the lower left leg that successfully responded to treatment with
      imiquimod cream 5%. Initial treatment included application of imiquimod from the
      knee to the ankle once daily. Application frequency was increased to up to 3
      times daily and eventually was switched to overnight occlusion until complete
      clearance was achieved. This rare condition is not completely understood, as only
      approximately 20% of cases have shown individual melanoma metastases within the
      pigmented skin. In our patient, as in the majority of cases, we were unable to
      detect individual metastases within the pigmented skin. This case is unique
      because diffuse melanosis was confined to an extremity. The clearing of the
      pigmented skin was impressive. Imiquimod may have activity against melanoma,
      melanoma in situ, and diffuse melanosis associated with melanoma, as demonstrated
      in our case.

PMID- 24738097
TI  - Nicotinamide and reflections on Alan Shalita and George Hambrick Jr.

PMID- 24738098
TI  - Basal cell carcinoma: analysis of factors associated with incomplete excision at
      a referral hospital in southern Spain.
AB  - Basal cell carcinoma (BCC) is the most prevalent malignancy, with excision as the
      best therapeutic approach. Incomplete excision of nonmelanoma skin cancer is a
      clinical indicator of the surgical technique performed. This retrospective study
      of 292 patients with BCC assessed the rate of incomplete excision in a tertiary
      referral hospital in southern Spain and its relationship with tumor location as
      well as histologic and surgical features.

PMID- 24738099
TI  - Microcystic adnexal carcinoma: review of a potential diagnostic pitfall and
      management.
AB  - Microcystic adnexal carcinoma (MAC) is an uncommon, locally aggressive cutaneous
      neoplasm that usually presents as a slow-growing, asymptomatic lesion on the head
      or neck. Microcystic adnexal carcinoma frequently is misdiagnosed due to its
      histologic appearance on superficial biopsy specimens mimicking other follicular
      neoplasms. Herein, we highlight a case in which a slow-growing lesion was
      initially diagnosed as a trichoadenoma following superficial biopsy; however,
      after surgical excision the pathology revealed a locally aggressive MAC.

PMID- 24738100
TI  - What is your diagnosis? Recurrent lobular capillary hemangioma with satellitosis
      (Warner and Wilson-Jones syndrome).

PMID- 24738101
TI  - Myofibroma.

PMID- 24738102
TI  - Solitary nodular lesion on the scalp.

PMID- 24738103
TI  - Thickened velvety plaques in a 75-year-old woman.

PMID- 24738105
TI  - Kaposiform hemangioendothelioma with Kasabach-Merritt syndrome mistaken for child
      abuse in a newborn.
AB  - Kaposiform hemangioendothelioma is a rare vascular neoplasm of childhood that may
      have an alarming and potentially misleading clinical presentation. Awareness of
      this entity is important to provide appropriate and immediate medical care. We
      report the case of a 24-day-old female newborn who presented with a large
      bruiselike lesion on the left leg. A diagnosis of cellulitis suspected to be
      secondary to child abuse was made and the patient subsequently was placed in
      foster care; however, the lesion did not resolve after treatment and relocation.
      On reevaluation at our institution, physical examination revealed a round, 3 x 4
      cm, violaceous, indurated, fixed, nonblanching, nontender plaque with an ivory
      center and peripheral erythema over the anteromedial aspect of the left leg.
      Biopsy demonstrated a vascular neoplasm consistent with kaposiform
      hemangioendothelioma (KHE), and laboratory evaluation revealed thrombocytopenia,
      low fibrinogen levels, and elevated D-dimer levels, confirming a diagnosis of
      Kasabach-Merritt syndrome (KMS).

PMID- 24738104
TI  - In the pipeline for psoriasis: upcoming psoriasis treatments.
AB  - Psoriasis is a chronic debilitating disease in which dermatologists take a
      frontline role in improving the quality of life of affected patients. Although
      recent years have seen the advent of numerous new medications for the treatment
      of psoriasis, there still is considerable room for improvement in our treatment
      of this condition. Novel insights into the underlying mechanisms of psoriasis
      have yielded exciting new potential medications, many with promising preliminary
      efficacy data. The upcoming systemic agents for the treatment of psoriasis are
      presented in this article, encompassing novel biologics and small-molecule
      medicines (eg, IL-17 receptor blockers, Janus kinase [Jak] inhibitors). The
      underlying mechanisms and currently available data for each drug will be
      discussed to impart a working knowledge of these new treatment options to
      dermatology residents, as these drugs may soon be added to our armamentarium for
      treating psoriasis.

PMID- 24738106
TI  - Reticular erythematous mucinosis.

PMID- 24738107
TI  - Granulomatous mycosis fungoides with clinical features of granulomatous slack
      skin.

PMID- 24738108
TI  - Pityriasis rubra pilaris triggered by photodynamic therapy with response to tumor
      necrosis factor alpha-blocking agents and acitretin.

PMID- 24738109
TI  - Epithelioid sarcoma: report of 3 cases.

PMID- 24738110
TI  - Introduction to special issue: Mechanisms and targets for prevention and
      treatment of colorectal cancer.

PMID- 24738112
TI  - A unified Bayesian hierarchical model for MRI tissue classification.
AB  - Various works have used magnetic resonance imaging (MRI) tissue classification
      extensively to study a number of neurological and psychiatric disorders. Various
      noise characteristics and other artifacts make this classification a challenging
      task. Instead of splitting the procedure into different steps, we extend a
      previous work to develop a unified Bayesian hierarchical model, which addresses
      both the partial volume effect and intensity non-uniformity, the two major
      acquisition artifacts, simultaneously. We adopted a normal mixture model with the
      means and variances depending on the tissue types of voxels to model the observed
      intensity values. We modeled the relationship among the components of the index
      vector of tissue types by a hidden Markov model, which captures the spatial
      similarity of voxels. Furthermore, we addressed the partial volume effect by
      construction of a higher resolution image in which each voxel is divided into
      subvoxels. Finally, We achieved the bias field correction by using a Gaussian
      Markov random field model with a band precision matrix designed in light of image
      filtering. Sparse matrix methods and parallel computations based on conditional
      independence are exploited to improve the speed of the Markov chain Monte Carlo
      simulation. The unified model provides more accurate tissue classification
      results for both simulated and real data sets.

PMID- 24738111
TI  - Effects of antipsychotics on bone mineral density and prolactin levels in
      patients with schizophrenia: a 12-month prospective study.
AB  - OBJECTIVE: Effects of conventional and atypical antipsychotics on bone mineral
      density (BMD) and serum prolactin levels (PRL) were examined in patients with
      schizophrenia. METHODS: One hundred and sixty-three first-episode inpatients with
      schizophrenia were recruited, to whom one of three conventional antipsychotics
      (perphenazine, sulpiride, and chlorpromazine) or one of three atypical
      antipsychotics (clozapine, quetiapine, and aripiprazole) was prescribed for 12
      months as appropriate. BMD and PRL were tested before and after treatment. Same
      measures were conducted in 90 matched healthy controls. RESULTS: Baseline BMD of
      postero-anterior L1-L4 range from 1.04 +/- 0.17 to 1.42 +/- 1.23, and there was
      no significant difference between the patients group and healthy control group.
      However, post-treatment BMD values in patients (ranging from 1.02 +/- 0.15 to
      1.23 +/- 0.10) were significantly lower than that in healthy controls (ranging
      from 1.15 +/- 0.12 to 1.42 +/- 1.36). The BMD values after conventional
      antipsychotics were significantly lower than that after atypical antipsychotics.
      The PRL level after conventional antipsychotics (53.05 +/- 30.25 ng/ml) was
      significantly higher than that after atypical antipsychotics (32.81 +/- 17.42
      ng/ml). Conditioned relevance analysis revealed significant negative correlations
      between the PRL level and the BMD values after conventional antipsychotics.
      CONCLUSION: The increase of PRL might be an important risk factor leading to a
      high prevalence of osteoporosis in patients with schizophrenia on long-term
      conventional antipsychotic medication.

PMID- 24738113
TI  - Evaluation of dronedarone as a therapeutic option for patients with atrial
      fibrillation.
AB  - WHAT IS KNOWN AND OBJECTIVE: Atrial fibrillation (AF) is the predominant
      dysrhythmia affecting approximately 2.4 million people in the United States and
      over 6 million Europeans. Dronedarone is a benzofuran derivative of amiodarone
      newly approved in 2009 for the treatment of AF. Here, we comment on the efficacy
      and safety of dronedarone in patients with AF. COMMENT: Eight randomized
      controlled trials were analysed in this article. Several trials showed that
      dronedarone therapy delayed AF recurrence, controlled ventricular rate and
      reduced incidences of hospitalization or death. However, some of the studies were
      terminated early due to an excess mortality rate. Further studies on long-term
      safety and trials on direct comparison to rate controlling medications are
      suggested to obtain additional insight of dronedarone. WHAT IS NEW AND
      CONCLUSION: Dronedarone reduces the incidence of AF recurrences, hospitalization
      and death in patients with paroxysmal or persistent AF. However, dronedarone
      should not be used in high-risk patients with permanent AF or patients with
      unstable chronic heart failure (HF) due to safety concerns.

PMID- 24738114
TI  - Increasing the uptake of peritoneal dialysis in New Zealand: a national survey.
AB  - BACKGROUND: Peritoneal dialysis (PD) has been shown to offer a high quality of
      life and independence to patients. New Zealand (NZ) is a world leader in home
      dialysis, yet over the last decade, rates of PD have been steadily decreasing for
      unknown reasons. OBJECTIVES: This paper reports on the findings of a national
      survey which explored the clinicians' perspectives on key factors that influence
      the rate of PD. DESIGN: Ten multi-answer questions were asked of several groups
      of dialysis health professionals to assess factors that are barriers and enablers
      to PD, including patient choice of dialysis modality, information about PD and
      pre-dialysis education delivery. All NZ nephrologists, pre-dialysis and PD nurses
      were invited to complete an anonymous online survey. Responses were analysed to
      identify perceived barriers and enablers influencing the rate of PD uptake
      amongst incident dialysis patients. RESULTS: Completed surveys were received from
      52% of nephrologists, 100% of pre-dialysis nurses and 50% of PD nurses in NZ. In
      NZ, patients are offered a choice of dialysis modality with pre-dialysis nurses
      delivering the majority of education. The most frequently identified barriers to
      uptake of PD were lack of information about PD, established misconceptions about
      PD and late referrals to dialysis. Important enablers were early and frequent pre
      dialysis education. The only two factors which were reported as very important
      contraindications to PD were dexterity and decreased cognitive function.
      CONCLUSION: Early and frequent pre-dialysis education encourages patients to
      choose PD and enables early identification and resolution of barriers to the
      uptake of PD.

PMID- 24738115
TI  - Normal and indeterminate pattern of fetal cardiotocography in admission test and
      pregnancy outcome.
AB  - AIM: The aim of this study was to evaluate the prognostic value of normal and
      indeterminate patterns of cardiotocography in admission test (AT) and pregnancy
      outcome. MATERIAL AND METHODS: A prospective study enrolled 818 intrapartum
      singleton pregnancies with gestational age of >34 weeks, in the latent phase and
      with intact membrane. Cases were divided into the high- and low-risk groups. Non
      Stress Test was interpreted according to the 2008 National Institute of Child
      Health and Human Development workshop. Adverse pregnancy outcomes were compared
      between groups based on AT interpretation. RESULTS: Out of 818 patients, 492
      (60%) were categorized as low-risk and 326 (40%) as high-risk pregnancies. In low
      risk patients, 410 (83.3%) had normal and 82 (16.7%) had indeterminate AT. These
      figures were 249 (76.4%) and 77 (23.6%) in high-risk patients, respectively, and
      two cases (0.6%) had abnormal AT. In both groups, thick meconium staining, non
      reassuring fetal heart rate pattern, cesarean section and cesarean section due to
      non-reassuring fetal heart rate pattern were significantly more frequent in
      indeterminate AT than normal ones (P < 0.001). In high-risk pregnancies with
      indeterminate AT, the risk of low birthweight and neonatal intensive care unit
      (NICU) admission increased. The positive predictive value was less than 30% in
      predicting thick meconium staining, non-reassuring fetal heart rate pattern, PH
      <= 7.2 and NICU admission in both groups. Overall, negative predictive value of
      AT for neonatal death and NICU admission was 100% and 96%, respectively.
      CONCLUSIONS: Indeterminate patterns of cardiotocography can predict adverse
      pregnancy outcomes and when facing this condition, obstetricians should act
      cautiously.

PMID- 24738116
TI  - Effects of body mass index and body fat percentage on gestational complications
      and outcomes.
AB  - AIM: The aim of this study was to investigate the correlation between body mass
      index (BMI), body fat percentage (BFP) and gestational outcomes. MATERIAL AND
      METHODS: Maternal- and infant-related data of gestation and gestational outcomes
      of 411 pregnant women were retrospectively analyzed. BMI was used to classify the
      women as obese, overweight, or normal. BFP was measured by the segmental multi
      frequency bioelectrical impedance method. The mothers' blood lipid profiles were
      assessed by automated chemical analysis. Logistic regression analysis was
      performed to determine the correlation of BMI and BFP with gestational
      complications. RESULTS: The rates of gestational diabetes and hypertension were
      significantly different between mothers who were obese (33.3%, 52.6%), overweight
      (10.3%, 32.2%) and normal (8.7%, 14.9%) (P < 0.001). The Apgar score at 1 min and
      intensive care unit admissions rate at birth were significantly different between
      infants born to obese (6.14 +/- 0.80, 14.0%), overweight (6.64 +/- 1.10, 8.9%)
      and normal (7.20 +/- 0.78, 1.9%) mothers (P < 0.01). The Apgar score at 5 min and
      the birthweights were not significantly different between these three groups (P >
      0.05). Additionally, the levels of serum total cholesterol (mmol/L), total
      triglycerides (mmol/L), and leptin (ng/mL) were significantly higher in obese
      (5.87 +/- 2.26, 2.04 +/- 1.65, 24.79 +/- 18.38) and overweight (5.29 +/- 1.85,
      1.74 +/- 1.05, 20.79 +/- 15.19) women, compared to normal women (4.89 +/- 1.05,
      1.45 +/- 0.77, 13.35 +/- 6.51) (P < 0.05). Furthermore, BFP was more strongly
      correlated to gestational diabetes (rs = 0.57 vs 0.68) and hypertension (rs =
      0.31 vs 0.43) than BMI. CONCLUSIONS: Obesity and overweight are associated with
      increased adverse maternal and neonatal complications. BFP is a more accurate
      predictor of gestational outcomes than BMI.

PMID- 24738117
TI  - Role of subcutaneous closure in preventing wound complications after cesarean
      delivery with Pfannenstiel incision: a randomized clinical trial.
AB  - AIM: The aim of this study was to evaluate the role of suture closure of the
      subcutaneous tissue in preventing wound complications after cesarean section with
      a Pfannenstiel incision, and to investigate factors associated with wound
      complications. MATERIAL AND METHODS: Patients undergoing cesarean delivery were
      randomly assigned to either suture closure or non-closure of the subcutaneous
      tissue. The participants were invited to two follow-up examinations at the 1st
      and 4th postoperative weeks for the detection of wound complications. The two
      main outcomes were composite wound complication and superficial wound separation.
      Factors associated with wound complications were analyzed using multiple logistic
      regression. RESULTS: During the study period, a total of 361 patients (176 in the
      closure group, 185 in non-closure group) were analyzed. Composite wound
      complication occurred in 23.3% (41/176) of the closure group, and in 20% (37/185)
      of the non-closure group with no significant difference (P = 0.44). Wound
      separation occurred in 2.3% (4/176) of the closure group and 1.6% (3/185) of the
      non-closure group without any significant differences (P = 0.64). None of the
      factors were found to be associated with the rate of composite complication. The
      significant factors found to be associated with wound separation were
      subcutaneous tissue thickness of 4 cm or more (P = 0.01) and maternal diabetes
      mellitus (P = 0.01), however they lost their significance in multivariate
      analyses. CONCLUSION: The rate of wound complications, including superficial
      wound separation, did not differ according to the subcutaneous closure in
      cesarean delivery with Pfannenstiel incision. It is not possible to predict wound
      complications using previously defined clinical and operative risk factors,
      including subcutaneous tissue thickness.

PMID- 24738118
TI  - Does lactation protect mothers against metabolic syndrome? Findings from the
      Tehran Lipid and Glucose Study.
AB  - AIM: We aimed to explore the effect of lactation on development of metabolic
      syndrome in a prospective population-based study. METHODS: From among 4028 female
      participants of the Tehran Lipid and Glucose Study, aged 15-50 years, without
      metabolic syndrome at the initiation of the study, 925 women were randomly
      selected to fill out the lactation questionnaire. Women were assigned to five
      groups based on lactation duration including: none, 1-6 months, 7-12 months, 13
      23 months and 24 months or more. Over a 9-year follow-up, metabolic syndrome was
      compared between these groups, before and after adjustment for possible
      confounding variables. RESULTS: Metabolic syndrome was developed in 12.1% of non
      lactating women; it was 28.6%, 34.0%, 26.2% and 26.7% in women with 1-6, 7-12, 13
      23 and 24 months or more of lifetime duration of lactation, respectively (P <
      0.002). Adjustment for confounders revealed that women with 1-6 and 7-12 months
      of duration of lactation had significantly higher odds of metabolic syndrome in
      comparison to 24 months or more (1.4 and 1.3 times, respectively). CONCLUSION: It
      seems that the longer duration of lactation up to 12 months may protect women
      against metabolic syndrome, in a dose-response manner.

PMID- 24738119
TI  - Exposure to ambient air pollutants and spontaneous abortion.
AB  - AIM: This study aimed to evaluate the correlation between ambient concentrations
      of air pollutants and first-trimester spontaneous abortion. MATERIAL AND METHODS:
      This was a retrospective case-control study, which was conducted on 296 women
      from June 2010 to February 2011 in Tehran, Iran. Cases were 148 women who
      experienced a spontaneous abortion before 14 weeks of gestation while the
      controls were 148 pregnant women after 14 weeks of gestation and groups were
      matched on sociodemographics and obstetrics characteristics. The samples were
      recruited randomly from 10 hospitals. In total, pollutants concentrations were
      collected at 29 stations hourly throughout the study area. We estimated the mean
      exposure for each participant and investigated the association between
      spontaneous abortion and ambient pollutants. RESULTS: Findings demonstrated that
      the average of ambient air pollutants in the cases was significantly higher than
      in the controls (P < 0.05). The odd ratios of abortion in the areas with higher
      concentrations of CO, NO2, O3 and PM10 were 1.98, 0.96, 0.94 and 1.01,
      respectively (P < 0.05). Also, the model showed that there was no significant
      association between prenatal exposures to SO2 and abortion (P > 0.05).
      CONCLUSIONS: Our findings suggest that pregnant women exposed to ambient air
      pollutants may be at increased risk of spontaneous abortion. Confirmation by
      further research is needed.

PMID- 24738120
TI  - Risk assessment of venous thrombosis in families with known hereditary
      thrombophilia: the MARseilles-NImes prediction model.
AB  - BACKGROUND: Although predicting the risk of venous thrombosis (VT) in an
      individual from a family with inherited thrombophilia is of major importance, it
      is often not feasible. OBJECTIVES: To develop a simple risk assessment model that
      improves prediction of the risk of VT for individuals of families with inherited
      thrombophilia. PATIENTS/METHODS: 1201 relatives from 430 families with inherited
      thrombophilia (deficiencies of antithrombin, protein C or protein S, and the
      factor V Leiden and F2 20210A mutations) were recruited at the referral center
      for thrombophilia in Marseilles, France, from 1986 to 2008. One hundred and
      twenty-two individuals had a personal history of VT. Sixteen preselected clinical
      and laboratory variables were used to derive the VT risk score. RESULTS: The
      scores based on the 16 variables and on the five most strongly associated
      variables performed similarly (areas under receiver operating characteristic
      curves of 0.85 and 0.83, respectively). For the five-variable score, named the
      MARNI score, derived from family history score of VT, von Willebrand factor
      antigen levels, age, severity of thrombophilia, and FGG rs2066865, the risk of VT
      ranged from 0.2% for individuals with a score of 0 (n = 186) to > 70% for
      individuals with a score of >= 7 (n = 27). The model was validated with an
      internal bootstrap method. CONCLUSIONS: With the use of a simple scoring system,
      assessment of the risk of VT in subjects from families with inherited
      thrombophilia can be greatly improved. External validation is now needed to
      replicate these findings.

PMID- 24738121
TI  - Comparative analysis of laparoscopy versus laparotomy in the management of
      ovarian cyst during pregnancy.
AB  - AIM: The aim of the present study was to evaluate the surgical and obstetric
      results of laparoscopy versus laparotomy in the management of ovarian cyst during
      pregnancy. MATERIAL AND METHODS: Sixty-nine eligible patients who met our
      criteria were randomly divided into the laparoscopy group (n = 33) and the
      laparotomy group (n = 36). The two groups were compared for their surgical and
      obstetric outcomes and the extent of pelvic adhesion discovered in later cesarean
      section (CS). RESULTS: The laparoscopy group had less blood loss (43 +/- 15 vs 51
      +/- 13 mL, P = 0.02), shorter postoperative hospital stay (2.9 +/- 0.5 vs 5.8 +/-
      0.6 days, P < 0.001), and lower postoperative pain score (2.7 +/- 1.2 vs 5.9 +/-
      1.5, P < 0.001) compared with the laparotomy group. The operative time, neonates'
      Apgar scores and birthweights between the two groups showed no significant
      differences (P > 0.05). Sixteen patients in the laparoscopy group, and 15
      patients in the laparotomy group underwent cesarean section. The filmy and dense
      type adhesion rate was significantly different between the laparoscopy group and
      the laparotomy group (6.25% vs 53.3%, and 0% vs 20%, respectively). CONCLUSIONS:
      The present results suggest that laparoscopy is a better choice than laparotomy
      for ovarian cyst during pregnancy, with less blood loss, less postoperative pain
      and less postoperative hospital stay. It offers a faster recovery, results in
      less pelvic adhesion and does not affect the fetus; however, studies encompassing
      larger numbers of cases are needed.

PMID- 24738122
TI  - History, pelvic examination findings and mobility of ovaries as a sonographic
      marker to detect pelvic adhesions with fixed ovaries.
AB  - AIM: To compare the performance of history and examination findings combined with
      transvaginal ultrasound (TVS) 'soft marker' evaluation of ovarian mobility for
      the prediction of fixed ovaries secondary to endometriosis at laparoscopy.
      METHODS: This was a prospective observational study performed at the University
      Gynecology unit, National Hospital of Colombo Sri Lanka. Women who were scheduled
      for laparoscopic assessment of their pelvis to investigate subfertility or
      chronic pelvic pain were enrolled. All women underwent history evaluation for
      dysmenorrhea and dyspareunia, vaginal examination and detailed presurgical TVS.
      TVS was used to assess 'soft marker' of ovarian mobility. 'Fixed' ovaries on
      ultrasound were defined as one or other of the ovaries being fixed or adherent to
      the internal iliac artery or pelvic sidewall laterally or to the uterus medially.
      These findings were compared with 'fixed' ovaries confirmed at laparoscopy.
      RESULTS: A total of 106 patients were analyzed. Mean age was 33.3 years (standard
      deviation, 5.1). Sensitivity, specificity, positive and negative predictive
      values of each of the screening methods against laparoscopy in detecting
      endometriosis were as follows: dyspareunia, 45.9%, 76.8%, 51.5% and 72.6%;
      dysmenorrhea, 75.7%, 69.6%, 57.1% and 84.2%; positive vaginal examination, 73%,
      88.4%, 77.1% and 85.9%; fixed ovaries with TVS, 78.4%, 94.2%, 87.9% and 89%; and
      a combination of history, examination findings and detection of fixed ovaries in
      TVS, 91.9%, 60.9%, 55.7% and 93.3%, respectively. CONCLUSION: A combination of
      clinical and TVS-based 'soft marker' of ovarian mobility provides a valid method
      for identifying fixed ovaries secondary to endometriosis.

PMID- 24738123
TI  - Survival and prognostic factors of patients with primary fallopian tube cancer
      receiving adjuvant paclitaxel and carboplatin chemotherapy.
AB  - AIM: To determine the survival and prognostic factors of patients with primary
      fallopian tube cancer (PFTC) who had been treated with paclitaxel and carboplatin
      chemotherapy. METHODS: The records of patients with PFTC who had been treated
      between 2002 and 2010, identified through the report of Chiang Mai University
      Hospital, were reviewed. All patients had pathological materials initially
      reported or reviewed by a gynecologic pathologist before initiation of treatment.
      RESULTS: Thirty patients met the inclusion criteria. Median age was 51 years.
      Serous adenocarcinoma was observed in the majority of patients (76.7%).
      Approximately 46% of patients were in stage I-II. The 5-year progression-free
      survival (PFS) for all patients was 37.2%. The 5-year PFS was 75.0% for stage I,
      51.4% for stage II and 18.5% for stage III. Median PFS of the entire cohort was
      26.0 months with a 95% confidence interval (CI) of 18.7-33.3 months. This rate
      was 18.5 months (95% CI, 6.7-35.6) for stage III whereas it was not reached for
      patients of stage I-II. Serous histology and stage were noted to be significant
      independent predictors of PFS with an adjusted hazards ratio of 7.54 (95% CI,
      1.34-42.4) and 6.19 (95% CI, 1.59-24.08), respectively. CONCLUSION: The 5-year
      PFS of the whole cohort was 37.2% with a median survival of 26 months.
      International Federation of Gynecology and Obstetrics stage and histological
      subtype were a significant independent factor for predicting PFS.

PMID- 24738124
TI  - The authors reply.

PMID- 24738125
TI  - Cardiac tamponade in pregnancy during the treatment of severe pre-eclampsia:
      report of a case.
AB  - We present a case of cardiac tamponade that occurred during the course of
      treatment for severe pre-eclampsia. A 37-year-old woman who underwent cesarean
      section for severe pre-eclampsia developed cardiac tamponade after delivery.
      While percutaneous pericardiocentesis temporarily improved her condition,
      pericardial effusion, dyspnea and tachycardia reappeared 5 days after delivery. A
      continuous drainage tube placed in the pericardial cavity for 5 days was required
      to maintain maternal cardiac function. Her clinical course was uneventful after
      continuous drainage and she was discharged 20 days after delivery. No such causes
      of symptomatic pericardial effusion were detected in the present case. Physicians
      should be aware of this complication when dyspnea is accompanied by tachycardia
      and enlargement of the cardiac silhouette with hypolucent lungs on chest X-ray.
      Immediate pericardiocentesis is also required to prevent life-threatening cardiac
      tamponade in such cases.

PMID- 24738126
TI  - Anaphylactoid reaction after use of intracervical dinoprostone gel.
AB  - Anaphylactic-like reaction or anaphylactoid reaction resembles generalized
      anaphylaxis but is not caused by immunoglobulin E-mediated allergic reaction.
      This reaction is caused by a non-immunologic mechanism even after first exposure
      to antigen. Prostaglandin E2 (dinoprostone) gel is commonly used for pre
      induction cervical ripening. We report a case of anaphylactiod reaction after
      insertion of prostaglandin E2 gel for induction of labor. Hyperstimulation with
      dinoprostone gel is reported in the literature. An isolated report of three cases
      of anaphylactiod reaction after intracervical dinoprostone gel was found during a
      literature search. We are reporting this case for its rarity. As a potentially
      life-threatening condition, every obstetrician should be aware of this rare
      complication of dinoprostone gel.

PMID- 24738127
TI  - Bifid scrotum and anocutaneous fistula associated with a perineal lipomatous
      tumor complicated by temporary bilateral cryptorchidism in utero mimicking
      ambiguous genitalia: 2-D/3-D fetal ultrasonography.
AB  - Ambiguous genitalia (AG) is a morphological diagnosis defined as genitalia not
      typical of a male or female. Findings mimicking AG, such as penoscrotal
      anomalies, anorectal malformations, and perineal lipomatous tumors, may prevent
      accurate identification of the fetal sex. We report a case of bifid scrotum and
      anocutaneous fistula associated with a perineal lipomatous tumor complicated by
      temporary bilateral cryptorchidism in utero, which were findings mimicking AG.
      Several perineal anomalies are associated developmental occurrences. In the
      present case, the combination of bifid scrotum and temporary bilateral
      cryptorchidism in the male fetus mimicked the combination of clitoromegaly and
      prominent labia, which are commonly observed in female fetuses. However, serial
      systemic assessments using prenatal 2-D/3-D ultrasonography and magnetic
      resonance imaging were unable to detect the anocutaneous fistula and
      differentiate the perineal lipomatous tumor. This case report suggests that the
      prenatal detection of perineal abnormalities may warn obstetricians of
      potentially undetected congenital perineal anomalies.

PMID- 24738128
TI  - Demonstration of the route of embryo migration in retroperitoneal ectopic
      pregnancy using contrast-enhanced computed tomography.
AB  - Retroperitoneal abdominal pregnancy is exceptionally rare. An unusual
      retroperitoneal pregnancy has a high risk of severe bleeding. Abdominal
      ultrasonography and whole abdominal computerized tomography scanning should be
      performed for the early diagnosis of ectopic pregnancy. A case of retroperitoneal
      ectopic pregnancy located very close to large retroperitoneal blood vessels and
      treated with resection is presented. Many unusual features of retroperitoneal
      ectopic pregnancy were highlighted as providing further evidence in support of
      the main proposed embryo migration mechanism via lymphatic vessels.

PMID- 24738129
TI  - The gross classification of hepatocellular carcinoma: usefulness of contrast
      enhanced US.
AB  - BACKGROUND: This study investigated the usefulness of postvascular images of
      contrast-enhanced ultrasonography (CE-US) in the gross classification of
      hepatocellular carcinoma (HCC) in comparison with contrast-enhanced CT (CE-CT)
      findings. METHODS: This is a prospective study with consecutive HCC patients who
      had both CE-US and CE-CT prior to surgical resection. Fifty-one patients (32 men,
      19 women; mean age, 68.9 years) with 61 HCCs were enrolled. The maximal diameters
      of all tumors ranged from 1.0 to 5.0 cm (mean +/- SD, 2.5 cm +/- 1.1). Weighted
      kappa statistics were used to assess the agreement of the sonographic or CT
      findings versus the results of macroscopic configurations. RESULTS: Thirty-nine
      tumors were macroscopically diagnosed as simple nodule type; 19 tumors were
      macroscopically diagnosed as simple nodular type with extranodular growth, and 3
      were macroscopically diagnosed as confluent multinodular type from the resected
      specimen. The diagnostic accuracy was 86.9% (53/61) for CE-US and 65.6% (40/61)
      for CE-CT. The differences in accuracy between CE-US and CE-CT were statistically
      significant (McNemar; p = 0.007). Agreement analysis between gross classification
      using CE-US and final macroscopic results gave a kappa value of 0.74 (95% CI:
      0.65-0.82), which was considered a good agreement. On the other hand, kappa
      coefficient value was 0.38 (95% CI: 0.28-0.48) between gross classification using
      CE-CT and final macroscopic results. CONCLUSIONS: CE-US is a more reliable tool
      than CE-CT to evaluate the gross type of HCC than CE-CT. Accurate gross
      classification using imaging is considered to be essential for the determination
      of the correct treatment strategy and the estimates of the patients' prognosis.

PMID- 24738130
TI  - Delayed intravesical mesh erosion in a midurethral sling following further mesh
      augmented pelvic prolapse surgery.
AB  - Intravesical mesh erosion and extrusion have been reported as devastating late
      complications of synthetic suburethral sling placement for the treatment of
      stress urinary incontinence. We report a case of a female patient with
      intravesical mesh erosion from a sling suspension that developed 4 years after
      primary prolapse surgery with mesh reinforcement. Intravesical mesh erosion was
      observed ultrasonographically and confirmed through cystoscopy. We excised the
      mesh via a vaginal approach and repaired both bladder mucosa and vaginal wall. As
      of this writing, the patient has been symptom-free for the past year post
      surgery. Long-term follow-up is recommended in such cases. Anti-incontinence
      surgery followed by primary prolapse surgery could potentially jeopardize the
      former. Complications may arise several years later so long-term follow-up is
      essential. Ultrasonography is an effective tool in evaluating mesh morphology and
      detecting intravesical mesh erosion.

PMID- 24738131
TI  - Embolization for pelvic arterial bleeding following a transobturator tape
      procedure.
AB  - The transobturator tape (TOT) procedure was devised to reduce morbidity, but
      nevertheless, it may cause significant complications. We treated a patient by
      pelvic arterial embolization due to severe arterial bleeding following the TOT
      procedure. The patient presented with vaginal bleeding and hematoma after the TOT
      procedure. She demonstrated bleeding from the left internal pudendal artery and
      was treated successfully by selective embolization. Although the risk of arterial
      injury during the TOT procedure is rare, pelvic surgeons should consider the
      possibility. Angiography with embolization should be considered for treatment of
      pelvic arterial bleeding following the TOT procedure.

PMID- 24738132
TI  - Poor prognosis of ovarian cancer with large cell neuroendocrine carcinoma: case
      report and review of published works.
AB  - Large cell neuroendocrine carcinoma (LCNEC) is well-reported to result in
      unfavorable prognoses in many organ cancers while being rarely reported in
      gynecologic cancer, especially ovarian and endometrial cancers. Here we report a
      case of ovarian cancer with LCNEC which spread to distant organs within 1 year of
      primary surgery despite the fact that the post-surgical stage was Ia. The case
      received platinum-based chemotherapy as an adjuvant therapy after her curative
      surgery. However, LCNEC in the case was resistant to the chemotherapy. In our
      review of published works, ovarian cancer cases with LCNEC show poor prognoses
      regardless of adjuvant chemotherapy following complete resection. Median overall
      survival was 10 months in stage I cases. Development of chemotherapy sensitive
      for LCNEC is needed.

PMID- 24738133
TI  - Endometrial hepatoid adenocarcinoma: a rare cause of elevated serum alpha
      fetoprotein.
AB  - Hepatoid adenocarcinoma is a rare and unusual tumor in the female genital tract.
      Hepatoid adenocarcinoma resembles hepatocellular carcinoma morphologically but
      develops in extrahepatic organs, and usually demonstrates foci of adenocarcinoma
      of the primary organ. Tumor cells often stain positive for anti-alpha-fetoprotein
      antibody, and may be associated with elevated serum alpha-fetoprotein, which may
      be useful as a tumor marker to guide treatment. There is little reliable
      information to guide clinical management of these unusual tumors and prognosis is
      poor despite multi-modal treatment. This report describes the diagnosis and
      treatment of this tumor in a postmenopausal woman.

PMID- 24738134
TI  - Primitive neuroectodermal tumor of the uterine cervix diagnosed during pregnancy:
      a rare case with review of literature.
AB  - Primitive neuroectodermal tumors of the cervix are very rare. A 28-year-old
      pregnant woman presented with a cervical mass. The tumor was staged as IB2. The
      biopsy from tumor was suggestive of malignant small round cell tumor. She then
      underwent termination of pregnancy followed by radical hysterectomy. Based on
      morphologic and immunohistochemical profile, a diagnosis of peripheral primitive
      neuroectodermal tumor of the cervix was made. The patient received adjuvant
      chemotherapy and radiotherapy. The patient is alive and disease-free 33 months
      post-surgery. The present case highlights the importance of keeping primitive
      neuroectodermal tumors in the differential diagnosis of small cell neoplasms of
      the uterine cervix. Pregnancy should not be a barrier to early detection and
      treatment of this potentially aggressive tumor. The optimal treatment methods
      have not yet been established because of the rarity of the tumor.

PMID- 24738136
TI  - Copy and paste.

PMID- 24738135
TI  - An engineered U1 small nuclear RNA rescues splicing defective coagulation F7 gene
      expression in mice.
AB  - BACKGROUND: The ability of the spliceosomal small nuclear RNA U1 (U1snRNA) to
      rescue pre-mRNA splicing impaired by mutations makes it an attractive therapeutic
      molecule. Coagulation factor deficiencies due to splicing mutations are
      relatively frequent and could therefore benefit from this strategy. However, the
      effects of U1snRNAs in vivo remain unknown. OBJECTIVES: To assess the rescue of
      the F7 c.859+5G>A splicing mutation (FVII+5A), causing severe human factor VII
      (hFVII) deficiency, by the modified U1snRNA+5a (U1+5a) in a murine model.
      METHODS: Mice expressing the human F7 c.859+5G>A mutant were generated following
      liver-directed expression by plasmid or recombinant adeno-associated viral (AAV)
      vector administration. The rescue of the splice-site defective pre-mRNA by U1+5a
      was monitored in liver and plasma through hFVII-specific assays. RESULTS:
      Injection of plasmids encoding the U1+5a rescued plasma hFVII levels, which
      increased from undetectable to ~8.5% of those obtained with the wild-type hFVII
      plasmid control. To assess long-term effects, mice were injected with low and
      high doses of two AAV vectors encoding the FVII+5A splice site mutant as template
      to be corrected by U1+5a. This strategy resulted in hFVII plasma levels of 3.9 +/
      0.8 or 23.3 +/- 5.1 ng mL-1 in a dose-dependent manner, corresponding in
      patients to circulating FVII levels of ~1-4.5% of normal. Moreover, in both
      experimental models, we also detected correctly spliced hFVII transcripts and
      hFVII-positive cells in liver cells. CONCLUSIONS: Here we provide the first in
      vivo proof of-principle of the rescue of the expression of a splicing-defective
      F7 mutant by U1snRNAs, thus highlighting their therapeutic potential in
      coagulation disorders.

PMID- 24738137
TI  - Anti-factor IXa/X bispecific antibody (ACE910): hemostatic potency against
      ongoing bleeds in a hemophilia A model and the possibility of routine
      supplementation.
AB  - BACKGROUND: We previously reported that a humanized anti-factor IXa/X bispecific
      antibody, hBS23, mimics the function of FVIII even in the presence of FVIII
      inhibitors, and has preventive hemostatic activity against bleeding in an animal
      model of acquired hemophilia A. After further molecular engineering of hBS23, we
      recently identified an improved humanized bispecific antibody, ACE910, for
      clinical investigation. OBJECTIVES: To elucidate the in vivo hemostatic potency
      of ACE910 by examining its effect against ongoing bleeds, and to determine its
      pharmacokinetic parameters for discussion of its potency for prophylactic use.
      METHODS: A nonhuman primate model of acquired hemophilia A was established by
      injecting anti-primate FVIII neutralizing antibody. When bleeds emerged following
      an artificial bleed-inducing procedure, either ACE910 or recombinant porcine
      FVIII (rpoFVIII) was intravenously administered. rpoFVIII was additionally
      administered twice daily on the following 2 days. Bleeding symptoms were
      monitored for 3 days. A pharmacokinetic study and multiple-dosing simulations of
      ACE910 were also performed. RESULTS: A single bolus of 1 or 3 mg kg-1 ACE910
      showed hemostatic activity comparable to that of 10 U kg-1 (twice daily) rpoFVIII
      against ongoing bleeds. The determined ACE910 pharmacokinetic parameters included
      a long half-life (3 weeks) and high subcutaneous bioavailability (nearly 100%).
      The simulation results based on pharmacokinetic parameters indicated that the
      above hemostatic level could be maintained with once-weekly subcutaneous
      administration of ACE910, suggesting the possibility of more effective
      prophylaxis. CONCLUSIONS: ACE910 may offer an alternative on-demand treatment
      option for patients with hemophilia A, as well as user-friendly and aggressive
      routine supplementation.

PMID- 24738138
TI  - G protein-coupled receptor kinase 2 moderates recruitment of THP-1 cells to the
      endothelium by limiting histamine-invoked Weibel-Palade body exocytosis.
AB  - BACKGROUND: G protein-coupled receptors (GP-CRs) are a major family of signaling
      molecules, central to the regulation of inflammatory responses. Their activation
      upon agonist binding is attenuated by GPCR kinases (GRKs), which desensitize the
      receptors through phosphorylation. G protein-coupled receptor kinase 2(GRK2) down
      regulation in leukocytes has been closely linked to the progression of chronic
      inflammatory disorders such as rheumatoid arthritis and multiple sclerosis.
      Because leukocytes must interact with the endothelium to infiltrate inflamed
      tissues, we hypothesized that GRK2 down-regulation in endothelial cells would
      also be pro-inflammatory. OBJECTIVES: To determine whether GRK2 down-regulation
      in endothelial cells is pro-inflammatory. METHODS: siRNA-mediated ablation of
      GRK2 in human umbilical vein endothelial cells (HUVECs) was used in analyses of
      the role of this kinase. Microscopic and biochemical analyses of Weibel-Palade
      body (WPB) formation and functioning, live cell imaging of calcium concentrations
      and video analyses of adhesion of monocyte-like THP-1 cells provide clear
      evidence of GRK2 function in histamine activation of endothelial cells. RESULTS:
      G protein-coupled receptor kinase 2 depletion in HUVECs increases WPB exocytosis
      and P-selectin-dependent adhesion of THP-1 cells to the endothelial surface upon
      histamine stimulation, relative to controls. Further, live imaging of
      intracellular calcium concentrations reveals amplified histamine receptor
      signaling in GRK2-depleted cells, suggesting GRK2 moderates WPB exocytosis
      through receptor desensitization. CONCLUSIONS: G protein-coupled receptor kinase
      2 deficiency in endothelial cells results in increased pro-inflammatory signaling
      and enhanced leukocyte recruitment to activated endothelial cells. The ability of
      GRK2 to modulate initiation of inflammatory responses in endothelial cells as
      well as leukocytes now places GRK2 at the apex of control of this finely balanced
      process.

PMID- 24738139
TI  - MiR-9 contributes to the developmental differences in CXCR-4 expression in human
      megakaryocytes.

PMID- 24738140
TI  - [Do not let low-level viremia occur in patients treated by antiretrovirals].

PMID- 24738141
TI  - Comparison of three reference methods for the measurement of intracellular pH
      using 31P MRS in healthy volunteers and patients with lymphoma.
AB  - 31P magnetic resonance spectroscopy (31P MRS) can measure intracellular pH (pHi)
      using the chemical shift difference between pH-dependent inorganic phosphate (Pi)
      and a pH-independent reference peak. This study compared three different
      frequency reference peaks [phosphocreatine (PCr), alpha resonance of adenosine
      triphosphate (alphaATP) and water (using 1H MRS)] in a cohort of 10 volunteers
      and eight patients with non-Hodgkin's lymphoma (NHL). Well-resolved chemical
      shift imaging (CSI) spectra were acquired on a 1.5T scanner for muscle, liver and
      tumour. The pH was calculated for all volunteers and patients using the available
      methods. The consistency of the resulting pH was evaluated. The direct Pi-PCr
      method was best for those spectra with a very well-defined PCr, such as muscle
      (pH=7.05 +/- 0.02). In liver, the Pi-alphaATP method gave more consistent results
      (pH=7.30 +/- 0.06) than the calibrated water-based method (pH=7.27 +/- 0.11). In
      NHL nodes, the measured pH using the Pi-alphaATP method was 7.25 +/- 0.12. Given
      that the measured range includes some biological variation in individual
      patients, treatment-related changes of the order of 0.1 pH units should be
      detectable.

PMID- 24738142
TI  - Non-uniformly under-sampled multi-dimensional spectroscopic imaging in vivo:
      maximum entropy versus compressed sensing reconstruction.
AB  - The four-dimensional (4D) echo-planar correlated spectroscopic imaging (EP-COSI)
      sequence allows for the simultaneous acquisition of two spatial (ky, kx) and two
      spectral (t2, t1) dimensions in vivo in a single recording. However, its scan
      time is directly proportional to the number of increments in the ky and t1
      dimensions, and a single scan can take 20-40 min using typical parameters, which
      is too long to be used for a routine clinical protocol. The present work
      describes efforts to accelerate EP-COSI data acquisition by application of non
      uniform under-sampling (NUS) to the ky-t1 plane of simulated and in vivo EP-COSI
      datasets then reconstructing missing samples using maximum entropy (MaxEnt) and
      compressed sensing (CS). Both reconstruction problems were solved using the
      Cambridge algorithm, which offers many workflow improvements over other l1-norm
      solvers. Reconstructions of retrospectively under-sampled simulated data
      demonstrate that the MaxEnt and CS reconstructions successfully restore data
      fidelity at signal-to-noise ratios (SNRs) from 4 to 20 and 5* to 1.25* NUS.
      Retrospectively and prospectively 4* under-sampled 4D EP-COSI in vivo datasets
      show that both reconstruction methods successfully remove NUS artifacts; however,
      MaxEnt provides reconstructions equal to or better than CS. Our results show that
      NUS combined with iterative reconstruction can reduce 4D EP-COSI scan times by
      75% to a clinically viable 5 min in vivo, with MaxEnt being the preferred method.

PMID- 24738144
TI  - Hemodialysis-associated cardiomyopathy: a newly defined disease entity.
AB  - Cardiovascular disease is the most common cause of the greatly elevated rates of
      mortality characteristic of patients undergoing maintenance hemodialysis. This
      article is an attempt to describe the complex and evolving features of cardiac
      disease routinely encountered in HD patients. Furthermore, by trying to
      appreciate the pathophysiological drivers, and the crucial interaction with the
      HD treatment itself, this article seeks to define cardiac disease in this setting
      (HD-associated cardiomyopathy) as a unique and complex entity. By understanding
      the phenotype and basis of HD-associated cardiomyopathy, we can develop an
      evolved understanding of the dominant processes involved in its development and
      offer up dialysis-based interventions specifically designed to mitigate the
      cumulative ischemic insults consequent to conventional HD treatment. This article
      explores the justification of this approach and recent evidence of its efficacy.

PMID- 24738143
TI  - Leading non-Gaussian corrections for diffusion orientation distribution function.
AB  - An analytical representation of the leading non-Gaussian corrections for a class
      of diffusion orientation distribution functions (dODFs) is presented. This
      formula is constructed from the diffusion and diffusional kurtosis tensors, both
      of which may be estimated with diffusional kurtosis imaging (DKI). By
      incorporating model-independent non-Gaussian diffusion effects, it improves on
      the Gaussian approximation used in diffusion tensor imaging (DTI). This
      analytical representation therefore provides a natural foundation for DKI-based
      white matter fiber tractography, which has potential advantages over conventional
      DTI-based fiber tractography in generating more accurate predictions for the
      orientations of fiber bundles and in being able to directly resolve intra-voxel
      fiber crossings. The formula is illustrated with numerical simulations for a two
      compartment model of fiber crossings and for human brain data. These results
      indicate that the inclusion of the leading non-Gaussian corrections can
      significantly affect fiber tractography in white matter regions, such as the
      centrum semiovale, where fiber crossings are common.

PMID- 24738145
TI  - Dialysis dosing for chronic hemodialysis: beyond Kt/V.
AB  - Current views regarding hemodialysis adequacy reach beyond indices of small
      solute removal such as Kt/V. Nevertheless, new Kt/V-based constructs such as the
      standard Kt/V, which adjusts not only for dialysis frequency, but which also
      represents removal of sequestered solutes rather than easily removed urea,
      continue to be useful. The scaling of dialysis dose to measures of size other
      than body water results in higher recommended doses of dialysis for children,
      small patients, and women, compared with the current body water-based scaling
      approach. Aside from small solute removal, increasing weekly time on dialysis
      results in slower removal of fluid with better tolerance and with increased
      removal of phosphorus, although both salt and water and phosphorus control often
      respond to efforts to reduce intake. The intermediate term benefits of removing
      larger middle molecules such as beta-2-microglobulin appear to be modest, and the
      benefits of removal of protein-bound uremic toxins remain to be proved in
      controlled trials.

PMID- 24738147
TI  - In-center nocturnal hemodialysis.
AB  - Dialysis intensification from conventional regimens (typically thrice weekly, 4
      hours per session) is increasingly utilized with the intent of improving the
      cardiovascular health and quality of life of chronic dialysis recipients. While
      home nocturnal hemodialysis offers the opportunity for maximal intensification of
      dialysis, it is inaccessible to the majority of dialysis recipients who are
      unable to self-administer hemodialysis in their own homes. In-center nocturnal
      hemodialysis (INHD) permits the intensification of conventional hemodialysis with
      the benefits of nursing support and supervision in addition to freedom from
      dialysis during productive daytime hours. Although no randomized trials have
      evaluated the relative merits of INHD, preliminary data indicate that INHD is a
      viable option that may confer a variety of benefits for chronic dialysis
      recipients.

PMID- 24738146
TI  - Clinical evidence on hemodiafiltration: a systematic review and a meta-analysis.
AB  - The general objective assigned to the European DIALysis (EUDIAL) Working Group by
      the European Renal Association - European Dialysis and Transplant Association
      (ERA-EDTA) was to enhance the quality of dialysis therapies in Europe in the
      broadest possible sense. Given the increasing interest in convective therapies,
      the Working Group has started by focusing on hemodiafiltration (HDF) therapies. A
      EUDIAL consensus conference was held in Paris on 13 October 2011 to discuss
      definitions, safety standards, clinical outcome and educational issues. Recently,
      the first report of the EUDIAL group was published, revisiting the definition,
      dose quantification, and safety of HDF. Since the meeting in Paris, new evidence
      has become available regarding the clinical benefits of HDF. This is the second
      report of the expert group in which the relation between HDF and clinical
      outcomes is systematically reviewed and analyzed, with emphasis on the relation
      between achieved convection volume and treatment effect.

PMID- 24738148
TI  - The changes of gap junctions between pituitary folliculo-stellate cells during
      the postnatal development of Zucker fatty and lean rats.
AB  - We investigated the effect of leptin on the postnatal development of gap
      junctions between folliculo-stellate cells by using Zucker fatty (fa/fa) rats
      that have defects of the functional leptin receptor. Male Zucker fatty rats
      (fa/fa) and male Zucker lean rats (+/+) were used at each of the following
      postnatal ages: 20, 30, 40, 50, 60, 70, 80, 90 days, and 1 year. On one of the
      aforementioned dates, the anterior pituitary glands were prepared for observation
      by transmission electron microscopy. We quantified the number of follicles and
      gap junctions, and calculated the rate of occurrence as the ratio of the number
      of gap junctions existing between folliculo-stellate cells per intersected
      follicular profile. In Zucker lean male rats, the number of gap junctions
      remained relatively constant from days 50 to 90 (0.44 +/- 0.02 to 0.49 +/- 0.03),
      and was similar in 1 year old rats (0.47 +/- 0.03). These data were statistically
      higher compared to Zucker fatty male rats. In Zucker fatty male rats, very few
      gap junctions were observed in 30-day-old rats (0.04 +/- 0.01: mean +/- SE). This
      disruption of gap junction formation persisted, and the number of gap junctions
      remained constant and showed a low level from days 40 to 90 (0.11 +/- 0.02 to
      0.17 +/- 0.02); this finding was similar in 1-year-old rats (0.17 +/- 0.02).
      These observations indicate that the effect of leptin over the gap junction
      formation within the anterior pituitary glands was directly mediated by
      interaction with the functional leptin receptor present on the folliculo-stellate
      cells.

PMID- 24738149
TI  - Effects of chemical agents on physical properties and structure of primary pulp
      chamber dentin.
AB  - This study evaluated the effects of chemical agents on the physical properties
      and structure of primary pulp chamber dentin using surface roughness,
      microhardness tests, and scanning electron microscopy (SEM). Twenty-five primary
      teeth were sectioned exposing the pulp chamber and were divided into five groups
      (n = 5): NT, no treatment; SH1, 1% sodium hypochlorite (NaOCl); SH1U, 1% NaOCl +
      Endo-PTC(r); SH1E, 1% NaOCl + 17% EDTA; and E, 17% EDTA. After dentin treatment,
      the specimens were submitted to roughness, microhardness testing, and SEM
      analysis. Roughness and microhardness data were submitted to one-way ANOVA and
      Tukey's test (P < 0.05). The SH1E group showed the highest roughness, followed by
      the E group (P < 0.05) when compared with the NT, SH1, and SH1U groups.
      Microhardness values of SH1 and SH1U showed no significant difference as compared
      to the NT (control) group (P > 0.05). Microhardness values could not be obtained
      in the EDTA groups (SH1E and E). The presence of intertubular dentin with opened
      dentin tubules was observed in the NT, SH1, and SH1U groups. SH1E showed eroded
      and disorganized dentin with few opened tubules and the intertubular/peritubular
      dentin was partially removed. Considering the physical and structural approaches
      and the chemical agents studied, it can be concluded that NaOCl and NaOCl
      associated with Endo-PTC(r) were the agents that promoted the smallest changes in
      surface roughness, microhardness, and structure of the pulp chamber dentin of
      primary teeth.

PMID- 24738150
TI  - Acute effects of splint immobilization of the forearm on in vivo microcirculation
      and histomorphology of the human skin.
AB  - BACKGROUND: Splint immobilization of the forearm is often performed in clinical
      practice. Previous studies investigated the effect of immobilization on bone,
      cartilage, muscle, and tendon, however, the acute effects on human skin
      microcirculation and histomorphology remains elusive. METHODS: In 12 healthy,
      nonsmoking individuals (aged 29.7 +/- 9.1 years) a randomly selected forearm was
      immobilized by splinting for 72 h, whereas the other forearm served as control.
      In vivo Reflectance-Mode Confocal-Microscopy (RMCM) was performed prior (baseline
      value) and postimmobilization to evaluate: quantitative blood cell flow; density
      of functional dermal capillaries; epidermal thickness; and granular cell size.
      RESULTS: At 72h forearm immobilization, quantitative blood cell flow was
      significantly reduced (42.86 +/- 3.68 cells/min) compared to the control blood
      flow (53.11 +/- 3.68 cells/min, P < 0.05) and dermal capillaries indicates less
      functional density (5.73 +/- 0.63 capillaries/mm2) compared to the controls (7.04
      +/- 0.81 capillaries/mm2, P < 0.05). Histometric assessment reveals significantly
      thinner epidermis following immobilization compared to the control site (40.02 +/
      2.91 vs. 46.64+/-3.09 um, P < 0.05). Granular cell size was significantly
      altered at 72 h splinting (730.1 +/- 42.53 um2) compared to the control cell size
      at 770.2 +/- 38.21 um2. Comparison of baseline values of both forearms indicate
      statistically insignificance (P > 0.05) for each parameter. CONCLUSION: At 72 h
      splint immobilization, for the first time, significant adaptive mechanisms were
      evaluated on human skin microcirculation and histomorphology using in vivo RMCM.
      These adaptations may be considered as an incipient atrophy of the human skin.
      Long-term effects of immobilization including the regenerative potential should
      be evaluated in further RMCM studies.

PMID- 24738151
TI  - Academic and nursing aptitude and the NCLEX-RN in baccalaureate programs.
AB  - Accurately predicting NCLEX-RN(r) success has a positive impact on all nursing
      education stakeholders. This study focused on the ability to predict NCLEX-RN
      pass rates on the basis of prenursing academic aptitude variables and the
      Assessment Technologies Institute (ATI) nursing aptitude program. The ATI
      predictors were the Test of Essential Academic Skills (TEAS) and fi ve ATI
      subject tests: Fundamentals, Medical Surgical, Nursing Care of Children, Mental
      Health, and Maternal Newborn. The prenursing variables comprised the prenursing
      grade point average, a prerequisite communication course, and the ATI TEAS
      composite subscores of TEAS Reading, TEAS Math, TEAS Science, and TEAS English.
      This study included participants from four baccalaureate nursing programs in the
      California State University system. Results of canonical correlation, multiple
      linear regression, and logistic regression revealed a significant correlation
      among prenursing, ATI scores, and NCLEXRN fi rst-try pass rates. Prediction of
      NCLEX-RN success rate using standardized testing data was supported, with the
      strongest predictors being the ATI Medical Surgical and ATI Mental Health tests.

PMID- 24738152
TI  - Microsecond simulations of DNA and ion transport in nanopores with novel ion-ion
      and ion-nucleotides effective potentials.
AB  - We developed a novel scheme based on the grand-canonical Monte Carlo/Brownian
      dynamics simulations and have extended it to studies of ion currents across three
      nanopores with the potential for single-stranded DNA (ssDNA) sequencing: solid
      state nanopore Si3N4, alpha-hemolysin, and E111N/M113Y/K147N mutant. To describe
      nucleotide-specific ion dynamics compatible with ssDNA coarse-grained model, we
      used the inverse Monte Carlo protocol, which maps the relevant ion-nucleotide
      distribution functions from all-atom molecular dynamics (MD) simulations.
      Combined with the previously developed simulation platform for Brownian dynamics
      simulations of ion transport, it allows for microsecond- and millisecond-long
      simulations of ssDNA dynamics in the nanopore with a conductance computation
      accuracy that equals or exceeds that of all-atom MD simulations. In spite of the
      simplifications, the protocol produces results that agree with the results of
      previous studies on ion conductance across open channels and provide direct
      correlations with experimentally measured blockade currents and ion conductances
      that have been estimated from all-atom MD simulations.

PMID- 24738153
TI  - Science, psychiatry, and thinking outside of the DSM: the Johns Hopkins approach.

PMID- 24738154
TI  - Update of the WHO/IUIS Allergen Nomenclature Database based on analysis of
      allergen sequences.
AB  - The IUIS Allergen Nomenclature Sub-Committee, under the auspices of the World
      Health Organization and the International Union of Immunological Societies,
      maintains the systematic nomenclature of allergenic proteins and publishes a
      database of approved allergen names on its Web site, www.allergen.org. In this
      paper, we summarize updates of allergen names approved at the meetings of the
      committee in 2011 through 2013. These changes reflect recent progress in
      identification, cloning, and sequencing of allergens. The goals of this update
      were to increase consistency in the classification of allergens, isoallergens,
      and variants and in the incorporation of the evolutionary classification of
      proteins into allergen nomenclature, while keeping changes of established names
      to a minimum in the interest of continuity. Allergens for which names have been
      updated include respiratory allergens from birch and ragweed pollen, midge
      larvae, and horse dander; food allergens from peanut, cow's milk, and tomato; and
      cereal grain allergens. The IUIS Allergen Nomenclature Sub-Committee encourages
      researchers to use these updated allergen names in future publications.

PMID- 24738155
TI  - On the translation of DSM-5 into Turkish.

PMID- 24738156
TI  - Selection bias: a missing factor in the obesity paradox debate.

PMID- 24738157
TI  - Use of camera phones for hospital clinical communication: patient perspectives.

PMID- 24738158
TI  - Medicine in small doses.

PMID- 24738159
TI  - The production of the eosinophil proteins ECP and EPX/EDN are regulated in a
      reciprocal manner.
AB  - Previous studies showed that the biological activity and the eosinophil content
      of eosinophil cationic protein (ECP, RNase 3) are determined by single-nucleotide
      polymorphisms (SNPs) in the ECP (RNase3) gene. In this study, we report the
      prevalence of a common SNP in the eosinophil protein x/eosinophil-derived
      neurotoxin (EPX/EDN, RNase2) and the association with the cellular contents of
      EPX/EDN and ECP. The genes were sequenced and the EPX/EDN405(G>C) rs2013109 SNPs
      were also determined by TaqMan 5'nuclease allelic discrimination assay. ECP and
      EPX/EDN in purified eosinophils or in whole blood extracts were analysed by
      sensitive immunoassays. The study included 379 non-allergic and allergic
      subjects. The genotype prevalence of the EPX/EDN405(G>C) polymorphism was GG 59%,
      GC 36% and CC 6%. The cellular contents of ECP and EPX/EDN were related in a
      reciprocal fashion with the sums of the protein contents being constant. The
      contents were associated with the ECP562(G>C) rs2233860 and EPX/EDN405(G>C) gene
      polymorphisms. The cellular content of eosinophil peroxidase (EPO) was not
      associated with the ECP and EPX/EDN genotypes. The prevalence of the
      EPX/EDN405(G>C) genotypes and the contents of the proteins were similar in non
      allergic and allergic subjects.The production and storage of the two ancestral
      proteins, ECP and EPX/EDN likely share common regulatory mechanisms, which result
      in opposing productions of the two proteins.

PMID- 24738160
TI  - Stromal cells can be cultured and characterized from diagnostic bronchoalveolar
      fluid samples obtained from patients with various types of interstitial lung
      diseases.
AB  - Increased proliferation of stromal cells is a typical feature encountered in
      several lung diseases. The objective of this study was to evaluate the success of
      standardized process for culturing stromal cells from small volumes of diagnostic
      bronchoalveolar lavage (BAL) fluid samples collected from various patients and to
      characterize the cultured cells. Small volumes (average 15 mL) of BAL fluid
      samples were collected from 98 patients who underwent bronchoscopy and BAL for
      diagnostic purposes. The cells were cultured in vitro and characterized by
      immunohistochemistry, electron microscopy, flow cytometry and differentiation
      tests. Cells could be cultured from 62% of samples with the success rate varying
      with the disease (p = 0.003). Cultures from samples of the patients with
      idiopathic pulmonary fibrosis, non-specific interstitial pneumonia, connective
      tissue disorder associated interstitial lung disease and allergic alveolitis had
      a higher success rate than samples derived from control lung (p < 0.001, 0.03,
      0.03 and 0.044, respectively). Smokers had a higher success rate compared with
      non-smokers (p = 0.035). The cultured cells were fibroblasts or myofibroblasts,
      but shared also similarities with progenitor-type cells. The study shows that
      mesenchymal cells can be cultured and studied from small volumes of diagnostic
      BAL fluid samples from patients with several different types of lung diseases.

PMID- 24738162
TI  - The $500 million idea: how CMS can help us achieve better care at a lower cost.

PMID- 24738161
TI  - Mecillinam resistance and outcome of pivmecillinam treatment in uncomplicated
      lower urinary tract infection in women.
AB  - Pivmecillinam (PIV) is a first-line antimicrobial for treatment of lower urinary
      tract infection in women (LUTIW). Mecillinam, the active substance of PIV, is
      bactericidal mainly against gram-negative uropathogens, whereas gram-positive
      species are considered intrinsically resistant. However, successful treatment of
      LUTIW caused by Staphylococcus saprophyticus has been reported, but more rarely
      for other gram-positive species. The aim of this study was to compare clinical
      and bacteriological outcome of PIV vs placebo treatment among uropathogens with
      special focus on mecillinam-resistant isolates. We analysed data from a
      prospective, multicentre, placebo-controlled, primary health care, therapy study
      performed in Sweden in 1995-1998 that included 1143 women with symptoms
      suggestive of LUTIW. Urine cultures were collected and symptoms registered at
      inclusion and at follow-up visits. Overall, the efficacy of PIV was superior to
      that of placebo. Clinical and bacteriological outcomes of PIV treatment were
      similar for S. saprophyticus, Escherichia coli as for most other uropathogens
      irrespective of their susceptibility to mecillinam. However, the occurrence of
      enterococci increased nearly fivefold shortly post PIV treatment, although with
      mild symptoms and a high spontaneous eradication. As susceptibility to mecillinam
      in vitro did not predict bacteriological and clinical outcome of PIV treatment,
      we suggest that the present breakpoints for mecillinam should be revised.

PMID- 24738163
TI  - ER is for emergencies: how washington turned bad public policy into good
      healthcare.

PMID- 24738164
TI  - [Background to forefront:sensor channels for cell death and homeostasis].

PMID- 24738165
TI  - [Author's reply by Laszlo Kiss regarding "Medical history references of the
      African journeys of Laszlo Magyar (1818-1864)"].

PMID- 24738167
TI  - [Empathy as a lived experience: a phenomenological analysis on the therapeutic
      relation].

PMID- 24738166
TI  - [To the editors regarding "Unrealized plans for medical journals before the
      launch of Orvosi Hetilap (Hungarian Medical Journal) by Sandor Dornyei].

PMID- 24738168
TI  - [What do we need to know about the burn injuries? Pathophysiology, aetiology and
      effects].
AB  - Burn injuries are a major public health problem worldwide, because they are very
      common. They are usually produced in domestic or work environments, although it
      is not unusual that they might be caused by traffic accidents or intentionally
      (self-injured or assaults on the people). These injuries do not attract much
      attention but if they are not treated properly, they can lead to serious systemic
      complications which can sometimes cause the death of the patient. In the last few
      years, the therapeutic approach of the burned patient has significantly improved
      due to an early correct initial valuation, which is used to design an effective
      nursing care plan and it determines the prescription of a suitable medical
      treatment according to the characteristics and the severity of the burn. The aim
      of this chapter is to explain some general aspects about the aetiology and
      pathology of burn injuries and their systemic effects, because the medical and
      nursing staff should know these aspects to make an adequate initial valuation.
      They should recognize the aetiology of the burn, its depth and area, its severity
      and its systemic complications to act properly in the initial phase of the
      treatment, because these preliminary actions are essential in the prognosis and
      evolution of the burns.

PMID- 24738169
TI  - [Local nursing care in burn injuries].
AB  - Burn injuries are tissue injuries originated as a result of a physical or
      chemical trauma. They can cause from a mild skin affectation to the total
      destruction of the affected tissues, depending on various levels of severity.
      Moreover, if the affected body surface is very large, patient life can be
      seriously compromised. An estimate 300 people for every 100,000 inhabitants are
      treated for burn injuries every year in hospitals or social-sanitary centers. In
      this chapter we aim at clarifying the nursing care for the affected area, once
      patient's life risk is stabilized and controlled.This care will be based on an
      adequate approach to local handling of burn injuries, after severity and
      prognosis have been stated.

PMID- 24738170
TI  - [Therapeutic guide to local care of burn injuries].
AB  - There is a large variety of topical application substances in the market for
      burnt areas treatment. This fact, far from being an advantage, turns into a
      serious problem when nursing staff has to choose the most adequate for each case.
      We think that, apart from a thorough knowledge of aspects such as indications and
      contraindications, application methods, combination with other substances and
      possible interactions, the formulation of a series of practical criteria can be
      of great help in order to select the right topical substance for the objectives
      pursued. This is the goal of this article.

PMID- 24738171
TI  - [Sequelae in patients with severe burns].
AB  - Nowadays, the main aim with severe burned patients is the prevention and
      treatment of the complications associated to burn injuries, because the mortality
      caused by them has significantly declined due to the improvements in the
      treatments used. This fact has changed the focus of the care from a biomedical
      model which pay attention to the physical aspects, to other based on the holistic
      care of the patient in which physical, psychological and social aspects are
      considered. To minimize the development of these adverse complications and to
      prevent their severity in long term, it is essential to initiate an early
      rehabilitation at hospital and follow these patients by the Primary Care team
      when they return home. The adverse effects of the burns can invalidate the
      patient and they can affect several spheres of his life: physical, psychological
      and social. The goals of this article are to determine the most common
      complications in severe burns, describe the treatments more effective to combat
      them and explain the role of nurses in the prevention and rehabilitation of these
      injured.

PMID- 24738172
TI  - [Therapeutic guide to critical burn patients].
AB  - Burn injuries are defined as the destruction of skin tissue under the effects of
      a thermal, electrical, chemical or radioactive agent. They can cause local
      injuries, with no systemic effect, but in certain cases, considered as "critical
      burn patients", they can produce severe and immediate systemic injuries, thus
      making it necessary to address care from a comprehensive perspective in order to
      achieve a satisfactory evolution. With this in mind, as nursing staff we must
      consider the need to review the treatments and nursing care we are applying to
      critical burn patients, in order to prevent the onset of complications that might
      lead to unwanted consequences or even the death of the patient, and eventually
      unifying criteria of nursing care. The main goal of this guide is to provide an
      efficient and easy to use working tool that is suitable for adult burn patients,
      thus making it easier for nurses to update knowledge and decision making.

PMID- 24738173
TI  - [Update on the treatment and care of scars].
AB  - Scars due to burns cause important aesthetic and functional squeal, causing
      psicologic disorders that can limit personal and social relationships of these
      patients. In this article we review the type of scars, the factors influencing
      its function, its characteristics, and we update the different options to prevent
      and treat pathologic scars in these patients. The text concludes with an
      exhibition of camouflage techniques of scars through make-up.

PMID- 24738174
TI  - [Physical rehabilitation in extensively burned patients].
AB  - The rehabilitation of the extensively burned patient aims to prevent and minimize
      consequences of the own lesion this is supported by three pillars: 1) postural
      treatment to prevent contractures; 2) kinesiotherapy to maintain/restore joint
      range of movement and muscle strength; 3) functional recovery. Physical therapy
      is essential in the multidisciplinary team. A coordinated team assures better
      results and positively influences the quality of life of the patients.

PMID- 24738175
TI  - [Psychosocial nursing care patient with major burns].
AB  - We must consider the patient as a human being from a holistic point of view; that
      is, not only from a physical point of view, but also from a mental emotional and
      spiritual perspective (not to be confused with religion). A patient with major
      burns is seen as a critical patient by the physician, and for him the most
      important issue is the survival of the patient. It is when the patient is
      admitted in the Burns Unit when the long and not easy road to recovery begins, in
      the understanding this is a new way to integrate, feel and ultimately learn to
      live again. The role of nursing during this journey will be vital. The prompt and
      better recovery of the patient will largely depend on the link established
      between nurse and patient, as well as his/her integration in the new life that
      awaits him. The following topics are developed in this article: Emotional
      evolution during his stage in the Burns Unit. Psychoemotional nursing care (fear,
      pain, image change, long hospital stay, resources). Management of the self
      protection measures of the nursing staff to maintain its own emotional stability.

PMID- 24738176
TI  - [Conclusions on the 3rd. Congress of the Spanish Society of Wounds].

PMID- 24738177
TI  - [Role for child neurologists].

PMID- 24738178
TI  - [A female neonate with skin eruption and eosinophilia].

PMID- 24738180
TI  - [The world of galactose and glucose: pathogenesis and therapy of lysosomal
      diseases].

PMID- 24738181
TI  - [Therapeutic strategies for muscular dystrophy: F based on the international
      guideline].

PMID- 24738179
TI  - [Basic pathogenesis of, heterogeneity of , and its therapeutic strategy for West
      syndrome and tuberous sclerosis complex].

PMID- 24738182
TI  - [Current status and future prospect of the therapy for muscular dystrophy].

PMID- 24738183
TI  - [Rehabilitation in muscular dystrophy].

PMID- 24738184
TI  - [To disseminate standard cares of muscular dystrophy; development of the Japanese
      clinical guideline for Duchenne muscular dystrophy].

PMID- 24738185
TI  - [Respiratory management of patients with Duchenne muscular dystrophy].

PMID- 24738186
TI  - [Development of novel therapeutic approaches for Duchenne muscular dystrophy].

PMID- 24738187
TI  - [Pathology understanding of developmental disorders seen from the structure and
      functions of the genome].

PMID- 24738188
TI  - [Clinical features in Rett syndrome: MECP2-, CDKL5- and FOXG1- related
      disorders].

PMID- 24738189
TI  - [Spread of X-chromosome inactivation into chromosome 15 is associated with Prader
      Willi syndrome phenotype in a boy with a t (X ; 15) (p21.1 ; q11.2)
      translocation].

PMID- 24738190
TI  - [Genetic analysis and genes relating synaptic function for autism spectrum
      disorder].

PMID- 24738191
TI  - [Disease susceptibility genes and genome structural abnormalities associated with
      developmental disabilities].

PMID- 24738192
TI  - [What should Japanese child neurologists do in order to solve the issues of off
      label prescription?--Focusing on the use of anti-psychotics in developmental
      disorders and the acquirement of public approval on the use of steroids in
      Duchenne muscular dystrophy].

PMID- 24738193
TI  - [Child neurology and development: basic lecture].

PMID- 24738194
TI  - [Peter Andreevich Kupriyanov (1893-1963)].

PMID- 24738195
TI  - [Results of surgical treatment of pulmonary atresia with ventricular septal
      defect and major aortopulmonary collateral arteries].
AB  - This article presents the 14-year experience of surgical treatment of pulmonary
      atresia with ventricular septal defect and pulmonary collateral blood bed. The
      surgery of defect was performed on 32 patients and they were followed up. The
      individual and differential approaches should be used in the choice of surgical
      strategy. This approach is based on the state of pulmonary arterial and
      collateral beds. An integral criterion of assessment was the common neo-pulmonary
      arterial index with boundary measure equal 150 mm2/m2. An application of given
      method allowed the performance of successful radical repair of defect in 15
      patients, 4 patients having been operated in one stage. The rest of the patients
      had the appropriate staged interventions. The lethality consisted of 9.4%.

PMID- 24738196
TI  - [Results of plasty of postinfarction left ventricular aneurysm performed on the
      working heart].
AB  - The results of plasty (124 patients) of postinfarction left ventricular aneurysm
      performed on the working heart are presented in this article. It is shown, that
      the upgrade of existing surgical techniques, which are directed to the creation
      of the optimal left ventricle shape, could improve the clinical results after
      plasty of postinfarction left ventricular aneurysm. It's important to arrange the
      conditions, which allow avoiding a negative influence on contractility function
      of the myocardium. The desired conditions could be obtained, if the plasty is
      performed on the working or fibrillating heart provided that the patient has a
      consistent aortic valve.

PMID- 24738197
TI  - [Treatment of giant diaphragmatic hernia].
AB  - The authors demonstrate the results of treatment (16 patients) with giant
      paraesophageal and posttraumatic diaphragmatic hernia. The article represents the
      main principles of operation management, key moments of the choice of access,
      operative techniques and also the features of the usage of modern reticular
      implants.

PMID- 24738198
TI  - [Mesh hiatal closure in antirelux surgery].
AB  - The article analyzes the experience of application of polymeric (mesh) implants
      for hiatal closure in patients with gastroesophageal reflux disease (GERD). The
      authors showed the main principles of the choice of mesh implants and
      recommendations to their usage. Principal technical stages of surgery are
      described. It is noted, that the application of prostheses had the high
      efficiency and safety in antireflux surgery.

PMID- 24738199
TI  - [The possibilities of gastroduodenal anastomosis reliability rising].
AB  - An experimentally-clinical assessment of reparative regeneration collagenation of
      gastroduodenal anastomosis was made. The anastomoses were formed by different
      ways: the inverted twin-row (classical) and everting one-row anastomosis. It was
      stated, that tissues repair on suture-line of the everting anastomosis took place
      faster and better (on a type of primary intention with wound epithelization on 3
      5 days). It was specified by comparatively smaller biophysical metabolic
      disorders in regenerative structures and characteristics of tissues adaptation
      (broad zone of anatomic alignment of submucous layer of gastric stump and
      muscular coat of duodenum stump) in anastomosis zone.

PMID- 24738200
TI  - [Video-laparoscopic interventions in diagnostics and treatment of torsion and
      necrosis of appendices epiploica].
AB  - A retrospective analysis of treatment of 82 patients with torsion and necrosis of
      appendices epiploica was made. The video-laparoscopic surgery of these patients
      was performed. When the diagnosis is unclear, the differential diagnostics should
      be made between the appendices epiploica disease and other abdominal diseases
      using the video-laparoscopy. This method allowed the establishment of the correct
      diagnosis of torsion and necrosis of appendices epiploica in 95.1% of patients.
      The laparoscopic treatment was made in 87.8% of cases with minimal quantity of
      postoperative complications. The video-laparoscopy allowed the detection of
      accompanying pathology of abdominal organs and performance of the correction by
      low-invasive method. The need of conversion occurred in 12.2% of patients.
      Postoperative period was characterized by uneventful recovery, minimal usage of
      analgesics and antibiotics, early stages of rehabilitation, perfect cosmetic
      effect in majority of patients.

PMID- 24738201
TI  - [The choice of polypropylene endoprosthesis for abdominal wall plasty].
AB  - The study (on 27rabbits) of postponed tissue reaction of abdominal wall was done
      after web space plasty of standard, light and superlight polypropylene
      endoprostheses on 30th, 60th and 120th days. It was stated, that the standard
      polypropylene prosthesis was the most suitable for endoprosthesis replacement of
      abdominal wall in strangulated ventral hernia. The light polypropylene
      endoprosthesis should be used in the uncomplicated hernia. The superlight
      polypropylene prosthesis should be applied for preventive endoprosthesis
      replacement of abdominal wall in its anatomico-functional insufficiency.

PMID- 24738202
TI  - [Characteristics of surgical approach using for patients with renal cell
      carcinoma, complicated by postcava tumor thrombosis].
AB  - The postcava tumor thrombosis had about 1/3 of patients with renal cell carcinoma
      at the initial examination. Reconstructive interventions were performed on the
      postcava for 38 patients (24 men, 14 women). The postcava thrombectomy was
      applied in 15 patients. The thrombectomy with postcava resection were carried out
      in 13 patients and plasty- in 6, prosthetics-in 4. An actuarial 3-year or 5-year
      survival rate of patients consisted of 59.4% and 42.2%. The performance of
      reconstructive interventions on postcava with its involvement was justified and
      provided satisfactory results in patients with renal cell carcinoma.

PMID- 24738203
TI  - [Phenomenon of ischemic steal syndrome in patients with different arteriovenous
      fistulas for hemodialysis and its surgical correction].
AB  - Patients with arteriovenous fistulas (648 cases) were examined for hemodialysis.
      The ischemic steal syndrome was detected in 47 patients and it was associated
      with vascular access for hemodialysis. A frequency of given complication was
      studied with correlation of the type of vascular access. The data of clinical and
      instrumental examination were described. It was revealed, that the development of
      steal syndrome was influenced by the blood circulation volume velocity on
      fistulas. Different reconstructive operations were performed on 42 patients in
      order to save the access for hemodialysis and eliminate the ischemia. The
      ligation of fistula was carried out for 5 patients. The survival of arteriovenous
      fistulas after reconstructive operations was till 46 months during the period of
      follow-up study.

PMID- 24738204
TI  - [Diagnostics and treatment of primary and secondary hyperparathyroidism].
AB  - The experience of treatment of 41 patients (aged 32-67 years) was presented in
      the article. The duration of disease was 2-5 years. Primary hyperparathyroidism
      was diagnosed in 16 patients and secondary--in 25. Diagnostics of the disease
      included clinical methods of treatment; studying levels of general and ionized
      calcium, phosphorus, parathormone; an ultrasound of thyroid and parathyroid
      glands, the substratum scintigraphy. All patients were undergone the operation.
      Adenomas of parathyroid glands were removed in the case of primary
      hyperparathyroidism including mini-access. Hyperplastic parathyroid glands (31/2)
      were disposed in the case of secondary hyperparathyroidism. Good immediate and
      long-term results were obtained.

PMID- 24738205
TI  - [Specification of the development risk of thromboembolic complications in
      abdominal surgery].
AB  - The retrospective research included 1983 patients with different abdominal
      surgical pathology. Parameters of homeostasis were estimated in preoperative
      period and early postoperative period. Frequency of occurrence and relevance of
      different clinical risk factors of thrombosis were analyzed. The rate of
      development of thromboembolic complications was investigated in studied subgroup
      of patients. It was revealed, that high risk groups of thrombosis progress were
      the patients with malignant disease of the pancreas, the esophagus, the large and
      straight intestine as well as obstructive jaundice of malignant genesis. The most
      significant clinical factors were the presence of malignant process, accompanied
      by cardiac pathology, dehydration and high number (3 and more) on ASA scale.

PMID- 24738206
TI  - [Prevention of eventration in diffuse suppurative processes in small pelvis].
AB  - The study was devoted to the problem of postoperative eventrations in
      gynaecological practice. Coaptation removable sutures were applied in order to
      prevent similar complications. Operations were performed in the cases of desolate
      condition of purulent disease of the uterus and uterine appendages with diffuse
      suppurative peritonitis. An advanced operative technique of suturing through all
      layers of abdominal wall demonstrated its high efficacy. No one patient (from 39)
      had the eventration or wound abscess.

PMID- 24738207
TI  - [Video-assisted thoracic lung resection in tuberculous patients].
AB  - The article showed the clinical experience using video-assisted pulmonary
      resection in tuberculous patients (47 operations). Upper lobectomy on the right
      was carried out in 10 (21.3%) cases. Upper lobectomy on the left was performed in
      6 (12.8%) cases. This fact could be explained by the frequency of affection of
      mentioned lung sites in tubercular process. A level of intraoperative
      complications consisted of 8.5% in video-assisted lung resections. The rate of
      postoperative complications was 10.6%. General efficacy of the application of
      video-assisted lung resections estimated 97.9%.

PMID- 24738208
TI  - [Surgical treatment of patients with lung cancer involving mediastinum organs
      with massive invasion in the thoracic aorta by using the extracorporeal
      circulation].
AB  - The patients (11 cases) with massive invasion in the thoracic aorta have been
      operated in the period from 2002 till 2010. The tumor of left lung was diagnosed
      in 9 cases and tumor of the mediastinum--in 2 cases. Prosthetics of the arch of
      aorta was performed under condition of artificial circulation in 6 cases. The
      prosthetics of the descending aorta was performed in 5 cases. A condition of
      artificial circulation was partially used in 1 case, fully used in one and the
      assist circulation was applied in 3 cases. The hospital lethality consisted of 4
      patients. The common number of patients with severe hospital complications was 5.
      The survival of one-, two- or three--year estimated 36.4 +/- 14.5%, 18.2 +/-11.6%
      and 0% respectively. A median of survival was 1,63 months. The remaining 7
      patients died in a long-term period. The cause of death was a progress of tumor
      process in vast majority of cases.

PMID- 24738209
TI  - [Osteosyntesis of ribs using the technology "matrix rib" in treatment of victims
      with multiple float rib fractures].

PMID- 24738210
TI  - [Successful treatment of patients with idiopathic necrosis of the forestomach].

PMID- 24738211
TI  - [Possibilities of combined treatment of stomach cancer with synchronous bilobate
      liver injury].

PMID- 24738212
TI  - [Successful iliofemoral shunting by synthetic prosthesis in the right side
      occlusion of iliac vein in patient with post thrombophlebitis and long persistent
      shin trophic ulcer].

PMID- 24738213
TI  - [Emergency abdominal surgery in the region of Russian Federation (an analysis of
      40 years)].
AB  - An analysis of the condition of emergency surgery for the patients with acute
      abdominal diseases was made in the period of 1972-2012. The dynamics of surgical
      beds provision and surgical personnel were taken into account. The authors
      investigated the rate of general and postoperative lethality, tendencies and
      regular occurrences and leading reasons of negative results in given diseases.
      Reserves of further decrease of the lethality were considered and it was
      associated with shortening of hospitalization part later than 24 hours. The
      future improvement of intensive therapy and resuscitation, more wide application
      of minimally traumatic techniques of surgical treatment could give better results
      in this group of patients.

PMID- 24738214
TI  - [Little known correspondence of the N.I and A. A. Pirogov family with T.
      Billroth].

PMID- 24738215
TI  - [Controversial questions of surgical strategy in obturative tumourous obstruction
      of the left colon].

PMID- 24738216
TI  - [Metabolic effects of bariatric surgeries].

PMID- 24738217
TI  - [Technological direction in the diagnosis and therapy of parasittic diseases:
      state-of-the-art and promises].
AB  - The paper presents information on the technological methods aimed at improving
      the diagnosis and prevention of parasitic diseases.

PMID- 24738218
TI  - [The problem of typing of tertian malaria foci in time and space].

PMID- 24738219
TI  - [Morphological identification of blastocystis].
AB  - The authors have attempted to systematize the currently known specific
      morphological features of the composition of Blastocystis spp. existing in
      different forms and to present this material as a reference table, by
      understanding the need for further data clarification. In addition, the paper
      describes observations of variations in the forms of human blastocysts. In
      particular, it depicts the species of multinucleated cysts, the identification of
      which may cause difficulties in diagnosing and differentiating these forms with
      some representative species of the genus Entamoeba.

PMID- 24738220
TI  - [Parasitological monitoring as part of epidemiological surveillance of
      helminthiasis in the Russian Federation].
AB  - The paper presents data on the prevalence of helminthiasis in Russia on the basis
      of the State Reports on the sanitary and epidemiological situation in the Russian
      Federation. It comparatively characterizes morbidity rates in 2010-2012.
      Morbidity analysis has revealed the main reasons for the prevalence of parasitic
      diseases and the possible ways of their elimination.

PMID- 24738221
TI  - [The first finding of invasive species Aedes (Finlaya) koreicus (Edwards, 1917)
      in European Russia].
AB  - For the first time mosquito Aedes koreicus were identified by morphology and
      molecular genetics in the south of European Russia (Sochi city) in 2013.

PMID- 24738222
TI  - [Pyrethroid resistance mechanisms in the body lice Pediculus humanus humanus L.:
      detoxification enzyme systems].
AB  - Synergists (piperonyl butoxide, MGK-264 (N-octyl bicycloheptene dicarboximide),
      DEF (S, S, S, tributyl phosphorotrithioate), and diethylmaleate) were used to
      investigate the metabolic resistance of body lice to permethrin. Instances of the
      synergistic activity ofpermethrin when combined with enzyme system inhibitors
      have been identified. The synergic ratios were 3.3 to 52.0 for monooxygenase
      inhibitors; 5.2 to 7.4 for esterases, and about 4 for glutathione-S-transferases.
      Since the use of the synergists did not lead to full inhibition of resistance, it
      was concluded that the lice had also a kdr-like type of resistance.

PMID- 24738223
TI  - [Detection of Babesia canis (Piroplasmida) DNA in the blood samples and lysates
      of the ticks Dermacentor reticulatus (Ixodidae) collected in the Tula and Moscow
      Regions].
AB  - Chimeric primers, the sensitivity and specificity of which allow them to be used
      in both the clinical setting and the epizootological assessment of tick infection
      by a real-time polymerase chain reaction (RT-PCR) assay, have been designed
      against Babesia canis infection. The findings suggest that a large number of
      Babesia DNA copies are detectable in the blood in acute babesiosis. Some animals
      that had experienced babesiosis developed blood B. canis carriage--a small number
      oftrophozoites remained alive for a long time. When babesiosis was suspected, its
      diagnosis could be confirmed by RT-PCR in half of dogs with subclinical signs.
      The tick concentration of Babesia ranged from several hundred to a few thousand
      parasites. There were no significant differences in the number of Babesia
      parasites in the infected ticks in relation to their collection site. However,
      the occurrence of infected ticks was significantly higher in the places of
      constant contact with a canine population, which is indicative of the decisive
      role of dogs in the intensity of an epizootic process in the foci of B. canis
      infection.

PMID- 24738224
TI  - [The involvement of some flea species in the epizootic process in the Gorno-Altai
      natural plague focus: spatial and temporary characteristics].
AB  - The relative number of plague pathogen strains isolated from some flea species in
      different Gorno-Altai natural plague foci substantially varies; this indicator
      also varies with time. These patterns are due to the difference in the structure
      of multispecies communities of ectoparasites in these areas and their long-term
      transformation. As of now, the three species Paradoxopsyllus scorodumovi,
      Ctenophyllus hirticrus, and Amphalius runatus are widely involved in pathogen
      transmission in all three foci. These ectoparasites should be referred to as main
      plague vectors. In each focus, they are joined by other flea species, such as
      Rhadinopsylla dahurica and Amphipsylla primaris in the Ulandryk focus,
      Frontopsylla hetera, R. dahurica, Paradoxopsyllus kalabukhovi, and
      Paramonopsyllus scalodae in the Tarkhatin focus, and P. scalonae and P.
      kalabukhovi in the Kurai focus, which should be classified as an additional
      vector.

PMID- 24738225
TI  - [Mammal flea (Siphonaptera) fauna in the interfluve of the Malaya Laba and Belaya
      Laba rivers].
AB  - The mammals in the interfluve of the Malaya Laba and Belaya Laba rivers were
      found to have fleas of 35 species; the main hosts for 2 of them were birds. Few
      hosts harbored most of animal parasites. The species composition and structure of
      fleas on small mammals greatly varies with high-altitude zones.

PMID- 24738226
TI  - [Blackflies (Diptera: Simuliidae) of North of Armenia].
AB  - The fauna of blackflies of North Armenia is represented by 12 species from the
      genus Simulium. The species composition in the Tavush Region is most diverse (10
      species) versus that in the Shirak (n = 5) and Lori (n = 3) Provinces, which is
      due to a wide variety of Simuliidae breeding sites. Among the bioregulators of
      blackflies, there are microsporidia of 4 species, cabbageworms (Mermithidae), and
      caddisflies of the genus Hydropsyche. There is a preponderance of microsporidia
      among the blackfly bioregulators. The highest percentage (60%) of the larvae
      infected with microsporidia is noted in the second half of summer, which is
      related to their environmental conditions.

PMID- 24738227
TI  - [The dynamics of the cercariosis situation in Moscow].

PMID- 24738229
TI  - [Comparative evaluation of the antihymenolepic activity of compounds of a series
      of salicylanilides (benzamides)].

PMID- 24738228
TI  - [The anthelminthic alinat and its antihymenolepic activity].

PMID- 24738230
TI  - [The problem of opisthorchiasis in Ukraine and current approaches to its
      treatment].
AB  - The opisthorchiasis epidemiological situation in Ukraine and the Sumy Region that
      has the largest natural focus of invasion has been analyzed. Its morbidity rate
      is 21.6 per 100,000 population, which is more than 20 times greater than that in
      Ukraine. The clinical course of the disease in the endemic focus, the attribute
      of which is the high percentage of its latent form, has been examined.
      Praziquantel is the most effective drug for the etiotropic therapy of
      opisthorchiasis.

PMID- 24738231
TI  - [Pseudoinvasion and transient carriage of the larvae of arthropods and soil
      nematodes in humans: problems and consequences. The authors' observations and a
      literature review].
AB  - The paper describes cases of pseudoinvasion and transient carriageof the larvae
      of arthropods and geohelminths. It highlights the objective and subjective
      factors in the diagnosis of arthropod-borne diseases and geohelminthiasis, which
      give rise to misdiagnosis. Distinctions between real invasion, transient
      invasion, and pseudoinvasion are pointed out. The fact that there are special
      problems with the misdiagnosis of people with mental diseases is emphasized. The
      key factors for preventing and diagnosing pseudoinvasions and transient carriage
      are defined.

PMID- 24738232
TI  - [Ways of improving the education of specialists from the health care
      organizations, agencies, and institutions of the Russian Inspectorate for the
      Protection of Consumer Rights and Human Welfare, in the area of parasitology].
AB  - The intensive modern Russian reforms in professional education require that
      stafftraining in medicine should be also improved. The main directions and ways
      of improving education in the specialty of Parasitology are as follows:--to
      update professional education, by applying a competence approach, in terms of
      which the main focus is on mastering the activity and obtaining the experience in
      make this activity in different situations;--to apply the modular principle in
      the design of educational programs and a teaching process;--to improve the
      fundamental training of staff in the area ofparasitology;--to enhance the
      integration of special, related, and basic disciplines in stafftraining.

PMID- 24738233
TI  - [Current methods for the diagnosis of human and animal clonorchiasis].
AB  - The paper briefly reviews the current techniques for the diagnosis of human and
      animal clonorchiasis, which involve visual, immunological, and polymerase chain
      reaction-based methods, including those extensively used in medical practice and
      devised in experimental research laboratories.

PMID- 24738234
TI  - [Urgency and improvement of sanitary and helminthological techniques of soil
      investigation].
AB  - From its inception, sanitary parasitology aimed at protecting the health of the
      population. But the procedures for sanitary and parasitological studies were not
      always so simple and effective as it was necessary. This article presents an
      analysis of the evolution of helminthological knowledge and the methods of soil
      investigation.

PMID- 24738235
TI  - [The 11th European Multicolloquium of Parasitology].

PMID- 24738236
TI  - [Microbial model Halobacterium salinarum in screening of synthetic analogues of
      antibiotic turbomycin A with anticancer activity].
AB  - The microbial test-system based on cultivation of Halobacterium salinarum
      developed earlier for screening inhibitors of sterol biosynthesis and proposed
      for screening anticancer antibiotics, proved to be efficient in revealing
      anticancer compounds among derivatives of tris(1-alkylindol-3-yl)methylium,
      synthetic analogues of antibiotic turbomycin A. Most of the methane sulfonate and
      chloride salts of such compounds, investigated with the help of the H. salinarum
      test-system, showed no activity (MIC>32 mcM), while several derivatives,
      containing N-butyl or N-pentyl substituents were rather active against the
      bacterial strain. The MICs of them against H. salinarum were 8 mcM for total and
      1 mcM for partial inhibition of the bacterial growth. The results of the study
      correlated with the results of other investigations that revealed anticancer
      activity of such compounds in tumor cell cultures. Therefore, the H. salinarum
      test-system demonstrated its availability for screening compounds with anticancer
      activity.

PMID- 24738237
TI  - [Protective activity of aqueous extracts from higher mushrooms against Herpes
      simplex virus type-2 on albino mice model].
AB  - Toxicity and antiviral activity of aqueous extracts from higher mushrooms such as
      Lentinula edodes (Berk.) Pegler (shiitake), Pleurotus ostreatus (Jacq.) P. Kumm.
      (oyster), Inonotus obliquus (Ach. ex Pers.) Pilat (chaga), Hydnellum compactum
      (Pers.) P. Karst. (compact tooth) were studied. In doses of 0.8 to 4.0 mg (dry
      weight) per mouse administered orally or intraperitoneally the extracts showed no
      acute toxicity. When the dose of the chaga extract was increased to 20 mg per
      mouse, a half of the animals died. Intraperitoneal administration of the aqueous
      extracts in a dose of 0.4-2 mg per mouse prior to the contamination by a single
      LD50 of Herpes simplex type 2 provided 100-percent survival of the animals
      exposed to the Lentinula edodes or Pleurotus ostreatus extracts and 90-percent
      survival of the animals exposed to the Inonotus obliquus or Hydnellum compactum
      extracts.

PMID- 24738238
TI  - [Estimation of MRSA susceptibility to oxacillin, cefoxitine, vancomycin and
      daptomycin].
AB  - Prevalence and therapy of infections due to MRSA remain one of the most serious
      problems in the world. Therefore, correct laboratory identification of the MRSA
      phenotype based on the use of the marker antibiotic cefoxitine, as a more
      susceptibile one vs. oxacillin, is of great importance. There is lately being
      observed a tendency towards emergence of strains with lower susceptibility to the
      last reserve drugs protecting from MRSA, i. e. vancomycin and daptomycin.
      Susceptibility of MSRA to these drugs was not investigated in Russia and there
      are no data on the prevalence of the VISA and hVISA phenotypes. The results of
      our study on estimation of susceptibility of 316 MRSA isolates from several
      regions of Russia to oxacillin, cefoxitine, vancomycin and daptomycin are
      presented herein. It was shown that the ranges of the oxacillin MIC were
      extremely wide, i. e. 0.5 to 512 mcg/ml, while 2.2 +/- 1% of the isolates was
      susceptible by the phenotype to oxacillin, in spite of the mecA gene presence. As
      for cefoxitine, the MRSA isolates were rather resistant to it at the MIC > 16
      mcg/ml. The tests with serial microdilutions revealed that 30.7 +/- 7% of the
      isolates had a critical level of susceptibility to vancomycin at the MIC 2
      mcg/ml. The E-tests revealed 1.3 +/- 1% of the isolates which were susceptible at
      the MIC 2-4 mcg/ml. The MRSA isolates were highly susceptible to daptomycin,
      while high levels of the MIC (2 mcg/ml) were characteristic of 2.8 +/- 1% of the
      isolates. Cross reduction of the susceptibility to vancomycin and daptomycin was
      observed.

PMID- 24738239
TI  - [Efficiency of a new synbiotic drink in treatment of chronic diseases of
      gastrointestinal tract and concomitant dysbacteriosis].
AB  - The efficacy of a novel synbiotic drink in the complex therapy of patients
      withchronic diseases of the gastrointestinal tract and concominant intestinal
      dysbacteriosis was investigated in a randomized trial. The synbiotic drink
      contains a probiotic strain of bifidobacteria and Fucus evanescens
      polysaccharides with prebiotic activity and broad spectrum of the biological
      action on the patients. The use of the synbiotic drink provided more evident
      reduction of the clinical symptomes, more efficient recovery of the intestinal
      microflora and higher percentage of the patients cure vs. the routine therapy and
      the therapy with inclusion of sour milk bifidobacterin.

PMID- 24738240
TI  - [Comparative efficacy of etiotropic therapy of patients with HBeAg-positive
      chronic hepatitis B (by the data of the international comparative placebo
      controlled study)].
AB  - Comparative placebo-controlled study entrolled 647 patients with verified
      diagnosis of chronic virus hepatitis B (HBeAg+), not previously subjected to
      antiviral therapy (with nucleotide analogues or interferons). The drug under the
      investigation was cycloferon, an earlier interferon inductor. The antiviral
      combination therapy of the main group patients (323 subjects) included the use of
      cycloferon + lamivudine for 48 weeks and the therapy of the control group
      patients (324 subjects) included the use of lamivudine + placebo for 48 weeks.
      The cycloferon and lamividine combination antiviral therapy was shown preferable
      vs. the lamivudine + placebo therapy by biochemical remission, virusological
      response, seroconversion by HBeAg by the 48th week of the treatment and HBsAg
      clearance. The conbination therapy provided lower frequency of the relapses
      within 24 weeks of the observation. The higher efficacy of the antiviral
      combination therapy was evident of the impact of the antiviral activity of
      cycloferon itself and its immunomodulating and interferon-inducing activity on
      elimination of the virus-infected hepatocytes. The use of the 48-week course of
      the antiviral combination therapy is advisable as the prime treatment in the
      management of patients with HBeAg-positive chronic hepatitis not previously
      treated with nucleoside analogues and as a variant of therapy for lamivudine
      refractory patients.

PMID- 24738241
TI  - [Cycloferon therapy of acute and chronic virus hepatitis C].
AB  - Complex clinical and laboratory examination of patients with HCV infection
      revealed that the use of cycloferon provided earlier normalization of the
      clinical and biochemical parameters and lower immunological imbalance vs. the
      basic therapy alone. High antiviral effect of the drug was shown. There was
      observed a positive impact of the cycloferon therapy on the late aftereffects
      hepatitis C, evidemt from higher frequency of the remissions in the patients with
      chronic hepatitis B and less frequent transformation of the acute form to the
      chronic one. Higher interferon-inducing and antiviral activities of cycloferon in
      the patients with acute hepatitis C and possible less frequent unfavourable
      aftereffects in the therapy with cycloferon in a dose of 500 mg were
      demonstrated.

PMID- 24738242
TI  - [Organic solvents for determination of bacterial endotoxin index in water
      insoluble pharmaceutical substances].
AB  - Substances for manufacture of parenteral drugs require control by the "Bacterial
      Endotoxin" (BE) index with the LAL-test. The aim of the study was to show
      possible applicability of organic solvents in BE determination by the gel-thromb
      test in case of water-insoluble pharmaceutical substances. The results confirmed
      that ethyl alcohol practically had no effect on the endotoxin activity. In the
      routine assays it is advisable to test solutions of the substances at the alcohol
      concentration of 6% below.

PMID- 24738243
TI  - [Demonstration of quality, safety and efficacy of biological products subject to
      changes in their manufacturing process].
AB  - Ensuring quality, safety and efficacy of the medicinal products placed on the
      market of the Russian Federation constitutes the area that requires strict
      regulation. When changes are made to the manufacturing process, the manufacturer
      generally needs to evaluate the relevant quality attributes of the product to
      demonstrate that modifications did not occur that would adversely impact the
      safety and efficacy of the drug. Where there is the lack of a sound legal basis,
      there is a need in harmonization of current Russian legislation with
      international and European rules governing medicinal product for human use to
      ensure quality, safety and efficacy thereof.

PMID- 24738244
TI  - [Implementation of the Madrid International Plan of Action on Aging in the CIS
      countries: the first 10 years].
AB  - In this article the information on policy action on aging in the CIS countries
      and Georgia (CIS+) are presented and discussed. The process of implementation of
      the Madrid International Plan of Action on Aging (MIPAA) from 2002 through 2012
      is chosen as a framework for analyzing the government policy on ageing. The
      article begins with a concise overview of the demographic situation in the CIS+
      countries, which belong to various stages of demographic transition. In its
      concluding part, the article presents the policy goals for implementing MIPAA
      during its third implementation cycle (2013-2017).

PMID- 24738246
TI  - [The age aspects of geomagnetic field action on the human].
AB  - The quantity of information about the influence of geomagnetic field (GMF) on
      human health increases. However, the age aspects of such influence still are of
      little studied. Earlier we suggested that GMF influence on reactions with such
      free radicals as nitric oxide (NO). It was shown that the content of NO in
      exhaled air falls with age. As NO is one of the factors neutralizing the action
      of free radicals during background radiation, the possibility of organism to
      eliminate the sequences with age falls. It drives to accumulation of mistakes in
      genome and elderly diseases.

PMID- 24738245
TI  - [Mechanisms of life span polymorphism maintenance in the house fly laboratory
      strains].
AB  - Assortative mating and hypervariability as the result of genomic stress, caused
      by selection, appear the main components of the mechanism of intrapopulation
      polymorphism maintenance. Activation of genome transposable elements has
      contributed significantly to increasing of variability provoked by inbreeding.
      Copy number of transposone Hermes DNA evaluation in somatic tissues of Musca
      domestica individuals from the strains differ by the life span at all
      developmental stages used as the criterion of genome stability. Investigations
      funded by RFBR 12-04-01450-a and 11-04-97005-r_povolzhje_a.

PMID- 24738247
TI  - [Regulatory T cells and aging].
AB  - Regulatory T cells with potent immunosuppressive properties have a pivotal role
      in the maintenance of immune homeostasis. This review highlights recent findings
      regarding the age-related changes in numbers and functional activity of human
      Treg-cells. Some of the mechanisms that keep the balance of Treg-cells during
      human aging are discussed. The possible roles of Treg-lymphocytes in pathogenesis
      of several diseases, associated with advanced age are also considered.

PMID- 24738248
TI  - [Buccal epithelium as an object for testing of biological age and the speed of
      aging].
AB  - Testing of biological age and the speed of aging is one of the main goal of
      gerontology and predictive medicine. This review summarizes the ability of using
      buccal epithelium as target of non-invasive investigation of aging diagnostics.
      Buccal epithelium used for thelomere test and morphological characteristics of
      its nucleus demonstrate the speed of aging. The electrophysiological
      investigation of buccal cells nucleus are the markers of biological age of a
      human. In future it can be possible to use buccal epithelium for
      immunogistochemical investigation with goal to diagnose cellular senescence.

PMID- 24738249
TI  - [The influence of age of donors on the ability of cells to homologous
      recombination DNA repair].
AB  - Old and young donors cells show different ability to homologous recombination
      (shown on the first stage--the chromosome transference) in vitro, that we suppose
      could be the reasons of the genome instability in aging. Homologous
      recombination, induced by X-radiation, is limited in cells taken from donors
      older than 70 years. Alpha-amanitin, the RNA-polymerize II repressor, in toxic
      doze, could induce the chromosome transference in the cells from all studied
      groups: from old and young donors and donors with repair process defect (with
      BRCA 1, 2 mutations). Summarized effect of X-radiation and alpha-amanitin does
      not increase the induction of the chromosome transference.

PMID- 24738250
TI  - [Age-dependent changes of neurochemical properties of sensory neurons].
AB  - Sensory neurons represent various groups of neurons differ on their
      morphological, immunohistochemical and receptor characteristics. The most of
      large neurons with myelinated Adelta fibers contain neurofilament 200 kD (NF200),
      some small afferent neurons can bind the isolectin B4 (IB4). Also, sensory
      neurons may include different types of tyrosine kinases (trkA, B and C) and
      neurotransmitters. Neuropeptides are generally located in small and medium-sized
      neurons. The proportion of neurons which contain trkA decreases and the
      percentage of NF200-, IB4-,substance P- and CGRP-positive neurons increases
      during the early development. Development of different types of sensory neurons
      fulfill under control of neurotrophins.

PMID- 24738251
TI  - [Survival and life span of Drosophila melanogaster in response to terahertz
      radiation].
AB  - Life span control is realized by an interaction of many genetic factors with
      environment. Due to development of new modern technologies based on non-ionized
      terahertz radiation (0,1-10 THz) the investigation of this radiation influence on
      living organisms becomes actual. In our study terahertz radiation effects on
      survival and life span of Oregon R line of Drosophila meanogaster were
      multidirectional depending on the age of the insects. Terahertz effect on
      survival was negative or neutral in the early life and positive in the later
      life. In Drosophila response to terahertz radiation sex differences were
      manifested. Males were not very sensitive to terahertz radiation. Irradiated
      female survival was increased significantly in the second half of imago life.
      Irradiation of Drosophila not influenced significantly on average and maximal
      values of life span, but the gap between the values of average life span of males
      and females in this group of insects was increased. Mechanisms of terahertz
      radiation effects on survival and life span maybe associated with changes in
      cellular membrane, gene expression and signaling pathways, controlling these
      properties.

PMID- 24738252
TI  - [Effect of dietary restriction during development on the level of expression of
      longevity-associated genes in Drosophila melanogaster].
AB  - It is well known that dietary restriction (DR) may substantially affect the life
      span (LS) of various model organisms including Drosophila melanogaster. In our
      recent studies, it has been revealed that the reduction of the content of main
      nutrients in larval medium may lead to an increase of flies' LS. Analysis of
      these data suggested that the most likely candidate for such long-term adaptive
      changes is insects' epigenome (i.e., persistent changes in the activity of genes
      that are not related to changes in the DNA structure). To examine whether the
      observed effects may be associated with long-term changes in the epigenetic
      regulation of genes associated with aging and longevity, in the present study we
      determined the level of expression of InR and Sir2 genes that are related to the
      effects of DR. In the larvae developed in DR conditions, the significant increase
      in the level of transcription of both these genes compared to the controls has
      been detected. The adult males have shown a significant increase in the level of
      expression of InR gene while no such changes were observed in females. The Sir2
      gene expression level was not different from the control level in adults of both
      sexes. It has been suggested that larval nutritional stress may lead to the
      induction of adaptive epigenetic rearrangements and, therefore, it can extend the
      flies' longevity.

PMID- 24738253
TI  - [The increase of the average and maximum span of life by the allogenic thymic
      cells transplantation in the animals' anterior chamber of eye].
AB  - The effect of the allogenic thymic tissue transplantation in the immune
      privileged anterior chamber of eye to the life expectancy of the recipient
      depending on its age was investigated. The thymic tissue transplantation from the
      young animals to the old ones leads to a significant increase in both the average
      and maximum life span of the recipient.

PMID- 24738254
TI  - [Age dynamics of functional parameters in men in the Polar region].
AB  - In order to test the hypothesis about rapid involution of functional parameters
      in residents in the Polar region, the functional parameters in men of 20-69 years
      have been compared in cross-sectional study. There is a tendency to a steady
      decrease of height, strength indices, parameter of muscle working capacity,
      balancing of the body when standing on one leg, vital capacity, cardiac output,
      tolerance to hypoxemia, level of physical health, adrenocorticotropic hormone and
      testosterone levels and an increase of body mass index, index of coordination
      (impairment of motor coordination), time of visual-motor response, systolic and
      diastolic blood pressure, index of functional changes, insulin level. More
      pronounced decline of functions is observed in men after 50 years.

PMID- 24738255
TI  - [Estimation the quality of life in elderly migrants of the Far North in the
      period of readaptation to new climatic conditions].
AB  - The article contains data about the peculiarities of indicators of the quality of
      life in elderly migrants of the Far North with arterial hypertension in the
      period of readaptation to new climatic conditions. Migrants of the Far North and
      residents of Krasnoyarsk revealed a moderate decline in the quality of life.
      Among all the factors reducing the quality of life of the subjects of study the
      most important is the need to be treated and to take drugs for chronic diseases.
      At the same time, the migrants of the Far North demonstrated a great reduction of
      the quality of life due to reduced activity in everyday life, dietary
      restrictions. The inhabitants of Krasnoyarsk showed the same due to reduction of
      income at retirement, reduced physical activity. At increase the terms of
      residence on arrival in the southern regions of Central Siberia the proportion of
      studied people with normal quality of life proved to be reduced and number of
      persons with a significantly reduced quality of life increases.

PMID- 24738256
TI  - [Role of intrarenal product TNF-alpha in the development of glomerular and
      tubulointerstitial tissues changes in elderly patients with diabetic
      nephropathy].
AB  - The aim of this study was to investigate the expression of TNF-alpha produced in
      the kidney in patients with diabetic nephropathy (DN) type 2 diabetes and its
      impact on the development of glomerular and tubulointerstitial tissue changes in
      these patients. The survey was conducted in 49 elderly patients (mean age 66.53
      +/- 3.50 years) with type 2 diabetes complicated by the development of DN. The
      study included patients with serum creatinine less than 0.13-0.14 mmol/l and in
      the initial stage of chronic renal failure in the level of serum creatinine less
      than 0.20 mmol/l. Diabetes duration was 17.89 +/- 0.44 years, and the duration of
      diabetic nephropathy was 1.60 +/- 0.44 years. Light and immunofluorescence
      microscopy of the renal biopsy specimens obtained by needle lifetime biopsy was
      performed for all patients. Morphological changes in the tissue were assessed in
      accordance with the latest international classification of diabetic nephropathy.
      In addition to light and immunofluorescence microscopy the expression of TNF
      alpha in the glomerulus and interstitial tissue by monoclonal antibodies labeled
      Fitc ("Dako", Germany) were determined in all patients. The location of TNF-alpha
      expression in the glomeruli (capillary loops, mesangial matrix, glomerular
      capsule) and in the interstitial tissue (urinary epithelium convoluted tubule
      basement membrane of urinary tubules, interstitial cells) were estimated.
      Correlation analysis of the influence of the expression of TNF-alpha on the
      expression of morphological changes of tissues revealed that a maximum of
      cytokine production in the glomeruli at the stage IIa class cytokine affected
      only the development of segmental glomerular sclerosis. With the decrease in TNF
      alpha production in the glomeruli you can observe the progression of histological
      changes--periglomerulyarny sclerosis development, builds thickening of the
      glomerular basement membrane; mesangial expansion goes from mild to severe and
      affects more than 25% of mesangial matrix (IIb stage), nodular lesions of
      Kimmelstil-Wilson are forming. Interstitial produce of TNF-alpha remains
      relatively high in the epithelium of the urinary tubules and in the interstitial
      cells of the kidney regardless of the class of diabetic nephropathy and influence
      the development of tubulointerstitial fibrosis.

PMID- 24738257
TI  - [Biological age estimation by means of electroencephalography].
AB  - The indices of computer electroencephalography have been estimated in 183 persons
      at the age of 20-89. Test-programs and the method of biological age determination
      by computer electroencephalography have been elaborated. We have found three
      subpopulations in each age group--people with slowing-down, mean and accelerated
      age changes rate. The proposed method of biological age determination includes
      standard generally established indices of computer electroencephalography.

PMID- 24738258
TI  - [Neuroprotective effects of peptides bioregulators in people of various age].
AB  - The review presents comparative characteristics of 2 peptide neuroprotective
      groups: polypeptide complexes (cortexin, cerebrolizin) and short peptides (semax,
      kortagen, pinealon). The data of clinical applying of peptides in elderly and old
      age people and cellular and molecular mechanisms of their neuroprotective
      activity is described.

PMID- 24738259
TI  - [Percutaneous transluminal coronary angioplasty, x-ray contrast researches and
      contrast-induced nephropathy in geriatrics].
AB  - The state-of-the-art review of literature on a problem of percutaneous
      transluminal coronary angioplasty in patients of the senior age groups with sharp
      cardiovascular pathology is submitted in three parts. In the third part the
      review on a problem of contrast-induced nephropathy in geriatric practice is
      submitted. Questions of the forecast, prevention and association with
      multimorbidity and chronic kidney disease are discussed.

PMID- 24738260
TI  - [Features of antiagregant and anticoagulant therapy at a hybrid revascularization
      of a myocardium in elderly and senile patients].
AB  - The hybrid revascularization of a myocardium combines advantages of mammaro
      coronary shunting and stenting of coronary arteries and represents the
      perspective direction in coronary heart disease treatment. This technique is of
      most value in patients of advanced and senile age, and also in patients of high
      surgical risk as it shows small injury, which enables to reduce and facilitate
      the postoperative period. However today, there is no single standard for the
      execution of these operations, in particular it is not clear, which scheme of
      antiagregant and anticoagulant therapy is worth adhering for greater efficiency
      of the procedures and patient safety.

PMID- 24738261
TI  - [Treatment of elderly and senile patients suffering from benign prostatic
      hyperplasia and chronic prostatitis].
AB  - In the clinical settings and in animal experiments the research was conducted on
      effectiveness and safety of treatment the benign prostatic hyperplasia, chronic
      prostatitis in the stage of active inflammation in elderly and senile patients.
      The method of treatment including transrectal fonoforez of the Russian
      preparation of Tisol (Tisolium, gel, the company "Olympus" Yekaterinburg) in
      combination with diclofenac sodium protected by patents of the Russian Federation
      was used. The developed method of treatment has shown high efficiency and safety,
      which is confirmed by experimental, clinical, laboratory and instrumental
      studies.

PMID- 24738262
TI  - [The structure of psychopathology associated with addictive disorders, against
      alcohol addiction and the possibility of it's neurometabolic correction in the
      elderly].
AB  - The article presents the analysis of the structure and dynamics of
      psychopathology associated with addictive disorders in elderly patients with
      alcohol dependence. In terms of syndromic approach the structure of neurotic
      disease in elderly patients with a verified diagnosis of mental and behavioral
      disorders associated with alcohol consumption was evaluated. In the overall
      structure of neurotic pathology in these patients the analysis of symptoms of
      neurotic diseases, the research of the structure of syndromes and their dynamics
      were carried out, as well as the patient's attitude to the disease and to its
      manifestations was determined. A factor model of the pathogenesis of neurotic
      pathology connected with mental and behavioral disorders due to alcohol use in
      elderly patients was developed. The high clinical effectiveness of the drug
      "Cytoflavin" used in the reduction of psychiatric symptoms in patients aged from
      62 to 74 years with a diagnosis of mental and behavioral disorders associated
      with alcohol consumption has been shown.

PMID- 24738263
TI  - [Features of psychopharmacotherapeutic correction of alcohol dependence in the
      elderly].
AB  - The article is devoted to the actual in modern medicine problem as the study of
      the prevalence of alcohol dependence and its psyhofarmacological correction in
      the elderly. It is shown that elderly and old age as a result of reduction of the
      reserve capacity of the organism for clinical pathology becomes addictive
      specific psychopathological features that affect the course of disease and
      maintenance of preventive treatment. On the basis of empirical evidence the
      authors prove that at the border severity of alcohol withdrawal syndrome the drug
      "Cytoflavin" has a fairly pronounced psyhofarmacological activity for older
      people with alcohol dependence.

PMID- 24738264
TI  - [Socio-economic and health organizational problems of emergency and out-patient
      care for elderly and senile patients with arterial hypertension (according to the
      sociological monitoring)].
AB  - The article contains data about the peculiarities of socio-economic and health
      organization factors in the rendering emergency and out-patient care for elderly
      and senile patients with arterial hypertension. The results of study of
      satisfaction by medical care quality depending on the age and gender of the
      patients are discussed. A large number of living alone and widowed patients among
      elderly patients is marked. About half of the respondents in both groups are low
      income; among middle-income respondents a low proportion of the elderly is
      observed. The majority of patients can be admitted to the doctor in the
      polyclinic no earlier than 2 to 7 days from the moment of entry. The obtained
      data should be taken into account when forming a model of medical-social care for
      patients with arterial hypertension in older age groups.

PMID- 24738265
TI  - [Medico-social and psychosomatic status of gerontostomatologic patients].
AB  - Assessment of medico-social and psychosomatic status of patients of the advanced
      and senile age having dental diseases was carried out. The results of the study
      show that the level of stomatological morbidity in this contingent of patients is
      rather high, and the treatment must be carried out with obligatory participation
      of doctors-interns and taking into account mental health of a person.

PMID- 24738266
TI  - [Outpatient care for elderly cancer patients during the last year of life].
AB  - The scope of medical care provided for the 4th clinical group elderly cancer
      patients in the city outpatient units both in clinics and at home during the last
      year including the last month of life as well as the number of patients who died
      at home on average per district doctor per year were studied. As it turned out,
      the scope of outpatient care provided in the community (alongside with the low
      level of inpatient admissions) is not sufficient. More than half of all visits
      during the last year are made in the last month of patients' life. Due to great
      burden and special meaning of this period of disease the development of a special
      protocol "palliative care for cancer patients at the end of life" is required.
      Outpatient care takes an important place in palliative care for the elderly
      therefore while setting up a regional palliative care system it is advisable to
      pay attention not only to inpatient units establishment but also develop
      palliative care provision at the primary medical care level.

PMID- 24738267
TI  - [Endovenous laser obliteration and combined phlebectomy for treatment of varicose
      veins in elderly and senile patients].
AB  - In the available literature, we have found no comparative data on the efficiency
      and safety of endovenous laser ablation (EVLA) and traditional phlebectomy in
      elderly and senile patients. According to our results, in elderly and senile
      patients, the pain syndrome is much less pronounced after EVLA as compared with
      phlebectomy, the frequency of ecchymosis with an area of more than 100 cm2 and
      distal thrombosis of deep veins is lower. In the analyzed groups, there are no
      significant differences in the frequency of post-surgical complications after
      surgical intervention. Both EVLA and phlebectomy eliminate pathological reflux of
      the great saphenous vein with the same degree of reliability, within the period
      of examination of 1 year. In elderly and senile patients, the time for return to
      daily activity is significantly reduced after EVLA as compared to that after
      combined phlebectomy.

PMID- 24738268
TI  - [The comparative analysis of the medico-social characteristics and objective
      somato-stomatology status in the patients who have worried at children's age the
      siege of Leningrad and their contemporaries].
AB  - The research is executed on 73 patients of the senile age who have worried in
      their childhood the siege of Leningrad and group of comparison--140 patients of
      comparable age. The comparative analysis of indicators of the medico-social,
      objective somatic and dental status at the patients who have worried at
      children's age the siege of Leningrad and their contemporaries, not being exposed
      extreme impacts of the siege is carried out. The essential increase in number of
      correlative communications between an indicator of a cumulative rating scale of
      somatic diseases and the stomatologic status at the patients of the senile age
      who have endured the siege is established.

PMID- 24738269
TI  - [Indicators of the oral health quality of life in geriatrics].
AB  - The literature review is submitted according to dental health in patients of
      different age groups in foreign countries and in the Russian Federation. The
      positive and negative aspects of available criteria of its assessment including a
      sociological component are analysed. Further researches, their prospects are
      defined by the need of development of new integrated indicators, in a complex and
      comprehensively characterizing the stomatologic status especially in patients of
      advanced and senile age in interrelation with the general level of health and the
      social status.

PMID- 24738270
TI  - [Features of living activity limitations of elderly people with heart ischemic
      disease after surgical myocardial revascularization].
AB  - The article presents a comparative analysis of vital activity restriction in
      patients with coronary heart disease (CHD) after surgical myocardial
      revascularization in elderly and working age patients. It is demonstrated that
      elderly patients have some features of vital activity restriction, which is
      necessary to take into account in medical social expertise and rehabilitation
      program development.

PMID- 24738271
TI  - [Analysis of disability resulting from cardiovascular disease patients of
      retirement age uptake bureau of medical and social examination in Saint
      Petersburg].
AB  - The article demonstrate data on the primary and re-disability in the elderly, due
      to coronary artery disease and the results of expert assessment of citizens in
      the Bureau of Medical and Social Expertise of St. Petersburg from 2006 to 2012.
      The features of the level, structure, dynamics and distribution by disability
      groups in the retirement age are presented in comparison with the group of
      disabled people of the able-bodied age. During 7 year period of observation the
      consistent decline in the number of disabled people in both age groups was
      revealed. The increase in the number of the first and the third group disabled
      persons and the decrease in the number of people with second group of disability
      was found. The dynamics of disability in the retirement age group was greater
      than in the group of able-bodied age.

PMID- 24738272
TI  - [Features of reperfusion therapy in old patients at acute coronary syndrome with
      segment st elevation and moderately reduced kidney function].
AB  - The article discusses approaches to reperfusion strategy in old patients
      according to baseline GFR defined by MDRD formula for admission to the hospital
      with a diagnosis of STEMI. The authors analyzed the complications and mortality
      rates, depending on the method of reperfusion while GFR < 60 mL/min per 1,73 m2.
      GFR is an aggravating factor that increases frequency of hospital and annual
      mortality and complication of AMI.

PMID- 24738273
TI  - [The method of cryotherapeutic correction for premature aging and permeability of
      the blood-brain barrier in Afghanistan veterans with initial manifestations of
      insufficient blood supply to the brain].
AB  - The levels of neurospecific peptides in the systemic circulation and the rate of
      biological aging of veterans of war in Afghanistan were studied. A significant
      increase in the level of matrix metalloproteinase-9 reflecting the increased
      permeability of the blood-brain barrier in the initial manifestations of
      insufficient blood supply to the brain was found. After a course of general
      aerocryotherapy the optimization of biological and cardiopulmonary age were
      marked, which indicates a slowing of the biological aging.

PMID- 24738274
TI  - [Statistical analysis of links between cancer and associated diseases].
AB  - We investigate dependencies between cancer morbidity and associated diseases. A
      statistical method that yields blocks of diseases with most significant influence
      on the cancer morbidity is described. Based on USA data about cause-specific
      mortality we select diseases which have maximum differences between distributions
      of associated diseases in a group of people which had cancer or died from it and
      a group of people which didn't have cancer. A medical interpretation of the
      results is discussed.

PMID- 24738275
TI  - [The cradle of military medicine].
AB  - The Kirov Military Medical Academy, included into the State Code of Particularly
      Valuable Objects of Cultural Heritage of the Peoples of the Russian Federation,
      plays an important role in national military-medical science and education during
      XVIII and XIX centuries. Today the Kirov Military Medical Academy consists of 7
      faculties, 63 departments (52 military departments and 11 civil departments), 31
      clinics (17 surgical clinics and 14 therapeutic clinics), center of
      extracorporeal detoxification, 3 departments, taking part in treatment and
      diagnostic process, 11 clinical subdivisions, research center consisting of 4
      research subdivisions and 2 laboratories, and also 14 research laboratories, 32
      supply subdivisions and publications department. Glorious staff and graduates of
      the Academy took part in all russian wars. All famous medical schools were
      founded in the Academy in XIX-XX centuries. At the present time the Kirov
      Military Medical Academy is the main military medical university, leading
      research center and treatment facility of the Armed Forces of the Russian
      Federation.

PMID- 24738276
TI  - [The Military Medical Academy's website].
AB  - The article deals with the organization of work, evaluation and optimization of
      the official web site of the Kirov Military Medical Academy. The website of the
      Kirov Academy is presented as a multifunctional IT tool for support of its
      activity. Tasks and functions of the Kirov Academy web site, as well as
      technological features of its work are listed. Some of its quantitative
      characteristics as a user tool for the access to information resources of the
      Kirov Academy are given. The description of the site structure and its pages are
      presented. The requirements for information materials submitted for posting on
      the site are set out. The data of webometric ranking of Russian institutions of
      higher education and research institutes are analyzed, the location of the
      Academy web site in this rating is shown. The areas for further improvement of
      the Academy web site, its structure and services are stated.

PMID- 24738277
TI  - [Rendering of primary health care to patients with trauma of visual organ].
AB  - This article is devoted to the actual problem of modern ophthalmology--primary
      health care in cases of mechanical ocular trauma. The article presents the
      information about the most common ocular trauma and secondary organs of eye,
      which can occur in the practice of the military doctor. The article includes
      epidemiological analysis of eye injuries in peacetime and wartime. The authors
      propose an algorithm for examining patients with damages of visual organs. They
      also suggest the most informative diagnostic techniques and manipulations that
      can be performed in a medical center of a military unit with the help of provided
      resources to the correct formulation of preliminary diagnosis and choice of
      evacuation destination of a wounded person. These diagnostic manipulations do not
      require special skills and can be carried out in a medical center of a military
      unit. In their article, the authors propose an approximate algorithm of
      therapeutic measures carried out using medicines of primary health care that can
      be performed in a medical centre of a military unit with a help of provided
      resources, with an indication of drugs, dosage and ways of injection. Performing
      the described list of simple treatment measures for eye care allows a high degree
      of probability to achieve the prevention of infectious and inflammatory
      complications of eye injuries and subsidiary organs. This article is intended to
      military doctors and paramedics.

PMID- 24738278
TI  - [The formation of the School of Military Neurosurgery of the Military Medical
      Academy].
AB  - The article is devoted to stages of formation of the school of military
      neurosurgery. Famous pioneers of this school were Vsevolod Galkin and Boris
      Samotokin. Their scientific works were based on personal experience of treatment
      for the battle scull and brain injuries during the Great Patriotic War. The main
      aim of the activity of the talented researcher Vitally Khilko was to develop
      microneurosurgery, neuroimmunology and fundamental researchers of cerebral blood
      flow pathology. Boris Gaidar and Valeriy Parfyonov reorganized the echelon
      neurosurgical care system in a relatively short time. This reorganization formed
      the basis of the modem principles of specialized neurosurgical care in armed
      conflicts. At the present time department of neurosurgery is the leading
      methodological and clinical center of military neurosurgery in Russia.

PMID- 24738279
TI  - [Surgery in the Academy: history, achievements and prospects].
AB  - The 215th anniversary of the Imperial Medical and Surgical Academy (now Military
      Medical) is a reason not only for celebration, but also is the moment of truth,
      connecting the great history of surgical development in Russian and its prospects
      in 21st century. The Kirov Military Medical Academy is the center of professional
      education for military surgeons. There is not only military medical research and
      practice, but also clinical. The main goal of the Academy is development of
      different schools of the Academy. These schools are the fundamental basis for
      researches and military-medical staff training able for any service during the
      peace and wartime. Nowadays the Academy is not only the leading institute on
      battlefield surgery and treatment of severe multisystem injuries, but also the
      training center for emergency medicine.

PMID- 24738280
TI  - [Clinical toxicology of the Academy: yesterday, today and tomorrow].
AB  - National toxicology school of the Kirov Military Medical Academy, demonstrates
      the unity of clinical and experimental approaches related to one purpose
      throughout its history--saving human life and health from exposure to toxic
      substances of chemical nature. For more than three centuries the russian science
      of toxicology has been steadily developing, often ahead of the world science. It
      helped to create the means of protection and develop methods of treatment for
      chemical lesions. Currently, toxicology departments of military field therapy and
      military toxicology and medical protection are actively involved in the current
      study of military medicine, restructuring policy to provide toxicological aid in
      the Armed Forces, the development and introduction of Innovative methods of
      diagnosis and treatment of victims of toxicological etiology.

PMID- 24738281
TI  - [Role of researchers and employees of the Military Medical Academy in development
      of the system of military medical supply].
AB  - The Military Medical Academy has been solving theoretical and practical issues,
      concerning development of military medical supply, for 215 years. At different
      time periods and according to needs of military medicine and pharmacy researches
      and employees of the Academy aimed efforts to: development of the theory and
      practice of medical supply organization, regulatory basis of the system of
      medical supply, development of new samples of medical equipment, development of
      medicine manufacturing technologies and methods of quality control, researches in
      the area of medicine radiochemistry, forensic chemistry and toxicology, herbal
      and mineral water analysis and etc. At the present time there are the following
      education programs at the Academy: "Pharmacy", magister program "Management of
      medical supply", program for resident physicians "Management and economics of
      pharmacy".

PMID- 24738282
TI  - [Military postgraduate courses at the Military Medical Academy: history, current
      state and prospects].
AB  - Training of scientific and scientific-pedagogical staff is one of the most
      important tasks of any high school. The problem of staff training arose in the
      Kirov Military Medical (Medical Surgical) Academy before its official foundation.
      In 1741 first scholars were sent abroad for the preparation of theses. The
      scholars were supposed to return to the hospital schools for teaching activity.
      Since 1802 scholars have defended their theses in the Academy. In 1858 special
      medical institute, the prototype of the Institute for postgraduate military
      studies was established. Many outstanding scientists studied in the Academy and
      brought name of the Academy into repute. At the present time, the Institute of
      postgraduate military studies (postgraduate) of the Kirov Military Medical
      Academy continues to train scientific staff. The Institute of postgraduate
      military studies remains one of the most successful institutes in Russia.

PMID- 24738283
TI  - [Stages of formation and development of the national military neurology and
      psychiatry].
AB  - The article is devoted to the stages of formation and development of military
      neurology and psychiatry in Russia. Scholars of anxiety and mental disorders
      department of the Medical and Surgical Academy (Military Medical) made great
      contribution to development of scientific and organizational peculiarities of
      these medical disciplines and many other allied studies. Authors analyze the
      contribution of military psychiatrists and neurologists to the modern concept of
      mental care delivery in peace and wartime, research focus ares and prospects of
      its development.

PMID- 24738284
TI  - [The first department of infectious diseases in Russia: history of formation,
      main achievements and prospects of the national infectology].
AB  - Russian first department of infectious diseases, which has great traditions and
      achievements, as of right is a brilliant constellation of national researchers
      and practitioners military infectology, not only brought the Kirov Military
      Medical Academy into repute, but also made a huge contribution to the development
      of the science of infectious diseases and the establishment of an effective
      system treatment and prevention of these diseases. This article outlines the main
      historical stages of infectology in the armed forces of our country, summed up
      the contribution of members of the Department of Infectious Diseases of the
      Military Medical Academy in medical science, marked modern progress and prospects
      of development of military infectology.

PMID- 24738285
TI  - [Through the pages of monograph "outstanding hygienists of Russia"].

PMID- 24738286
TI  - [Homo sum: memoirs of Aleksey Petrovitch Bystrov].

PMID- 24738287
TI  - [Features of resistance formation to beta-lactam antibiotics in Francisella
      tularensis subsp. mediasiatica].
AB  - AIM: Determination of penicillin resistance features in tularemia causative
      agents of the mediasiatica subspecies, stability evaluation of differences in
      strains of various taxa and development of a rapid method of F. tularensis
      intraspecies differentiation. MATERIALS AND METHODS: Beta-lactamase activity was
      determined in 30 strains of Francisella genus bacteria by quantitative iodometric
      method. RESULTS: All the strains regardless of subspecies membership were
      characterized by high resistance to beta-lactam antibiotics, and bacteria of the
      mediasiatica subspecies in contrast to other francisella did not synthesize beta
      lactamase. Our attempts to induce beta-lactamase activity in vitro and in vivo in
      strains of this subspecies did not succeed. A method of intraspecies
      differentiation of F. tularensis by nitorcefin disks is proposed based on the
      distinctive feature. CONCLUSION: A high level of F. tularensis subsp.
      mediasiatica resistance to beta-lactams in vitro and their inefficiency during
      therapy of experimental tularemia due to a beta-lactamase negative strain
      suggests that F. tularensis beta-lactamase is not the leading factor in formation
      of native penicillin resistance of tularemia causative agent.

PMID- 24738288
TI  - [Actual problems of vaccine prophylaxis in the Russian Federation].
AB  - The WHO within the framework of extended immunization program assumes a
      significant increase of the number of vaccine controlled infections by 2020 -
      2025 to 27 - 37 including protection from diseases of parasitic etiology. Russia
      contributes to the international efforts of the WHO to control infections with
      vaccine prophylaxis. The national calendar of prophylaxis vaccinations currently
      provides vaccination against 11 infections--tuberculosis, hepatitis B,
      poliomyelitis, pertussis, diphtheria, tetanus, measles, rubella, epidemic
      parotitis, influenza, haemophilus type B infection. Significant progress in
      reduction of infectious morbidity controlled by means of specific prophylaxis has
      been made in the country.

PMID- 24738289
TI  - [Immunobiological properties of Bordetella pertussis lipopolysaccharide in the
      acellular pertussis vaccine].
AB  - AIM: Study of Bordetella pertussis lipopolysaccharide (LPS) immunobiological
      properties in the acellular pertussis vaccine. MATERIALS AND METHODS:
      Experimental series of acellular pertussis vaccines (APV), lyophilized LPS were
      used. Antibody titers against LPS in mice sera were evaluated by using EIA with
      peroxidase conjugate of anti-species antibodies against mice IgG. LPS activity in
      B. pertussis antigen complex preparations was determined in quantitative
      chromogenic LAL-test by end point. APV protective activity was determined in mice
      test during intracerebral infection by B. pertussis strain No. 18323 virulent
      culture. APV safety was determined in the mice body weight change test. RESULTS:
      The presence of LPS in APV was shown in immune electrophoresis with purified B.
      pertussis LPS preparation as a control. Formalin treatment changes immunochemical
      properties of APV LPS that lead to the shift of precipitation bands with
      pertussis agglutinating sera from the start zone into cathode. The quantity of
      LPS in pertussis culture supernatants was on average 49050 +/- 6774 endotoxin
      units per ml (EU/ml). In APV preparations the quantity of LPS was on average 906
      +/- 90 EU/ml, i.e. decreased by more than 50 times. An increase of antibody
      titers against B. pertussis LPS in mice sera after the APV immunization was shown
      in EIA, which gives evidence of its presence in immunogenic form in the complex
      preparations. The preclinical studies carried out show protective activity and
      specific safety of the experimental APV series. CONCLUSION: Formalin-neutralized
      APV preparation is a complex of protein antigens in association with LPS.
      Formalin treatment results in modification of LPS molecule that retains antigenic
      properties but is significantly less toxic.

PMID- 24738290
TI  - [Influence of various bacterial ligand application methods on cytokine
      expression].
AB  - AIM: Study the production of cytokines in mice during vaccination with
      polycomponent Immunovac-VP-4 vaccine containing TLR ligands with various
      administration methods. MATERIALS AND METHODS: Immunovac-VP-4 was administered to
      mice by subcutaneous, intranasal or per oral methods. The preparation was
      administered nasally at a single dose of 500 microg in the volume of 30 microl.
      Per oral single dose was 2000 microg in the volume of 0.5 ml. 200 microg of the
      preparation was administered subcutaneously. Cytokines in blood sera were
      determined by EIA 8 hours after the administration of the vaccine. RESULTS: In
      mice 8 hours afterthe single administration of Immunovac-VP-4 the levels of IL
      1beta, IL-6, IL- 12, IL-5 increased significantly. However their concentration
      differed depending on the method of administration. The most active expression of
      cytokines was observed during subcutaneous administration. The indexes of
      cytokine expression were significantly higher (p < 0.05) than during non
      parenteral administration methods. CONCLUSION: Mucosal application methods along
      with parenteral were established to be able to activate effector mechanisms of
      immune repose with its consequent polarization by Th1/Th2 pathways. These
      mechanisms lay the groundwork for development of antigen-specific immune
      responses against antigens/pathogens.

PMID- 24738291
TI  - [Production and properties evaluation of monoclonal antibodies against
      Pseudomonas aeruginosa exotoxin A].
AB  - AIM: Production, study of properties and evaluation of a possibility to use
      monoclonal antibodies against Pseudomonas aeruginosa exotoxin A (ETA) for the
      detection of molecules of recombinant exotoxin A and anatoxin. MATERIALS AND
      METHODS: Producer hybridomas for monoclonal antibodies against ETA were
      generated. Recombinant exotoxin A, its atoxic forms, P. aeruginosa anatoxin and
      P. aeruginosa PA-103 live culture were used for immunization of mice. RESULTS:
      The experiment of fusion of malignant cell line with immune lymphocytes obtained
      from a mouse immunized with recombinant ETA turned out to be the most productive.
      Intensity of interaction of monoclonal antibodies with recombinant atoxic forms
      of ETA was evaluated in enzyme immunoassay. Protective (toxin-neutralizing)
      activity of antibodies in cell culture and the ability to detect exotoxin A in
      latex-agglutination reaction were studied. Antibodies of hybrid culture No. 21
      are able to detect molecules of recombinant ETA and anatoxin in the latex
      agglutination reaction. CONCLUSION: Use of the antibodies produced for testing
      toxigenicity of P. aeruginosa strains as well as detection of anatoxin in the
      technological process of production of prophylaxis preparations based on exotoxin
      A is expected.

PMID- 24738292
TI  - [Features of dynamics of sera cytokines in patients with erythema multiforme
      during immunotherapy].
AB  - AIM: Study the features of cytokine profile in patients with exudative erythema
      multiforme (EME) and dynamics of basal level of pro-inflammatory and anti
      inflammatory cytokines during immunotherapy. MATERIALS AND METHODS: 39 adult
      patients with erythema multiforme were examined. The patients were split into
      groups based on therapy variant. One group (14 individuals) received Immunovac-VP
      4 against the background of basic therapy; the other (12 individuals)--cagocel
      against the background of basic therapy; comparison group (13 individuals)
      received only basic therapy; 15 individuals composed a group of healthy
      individuals. All the patients had the level of pro-, anti-inflammatory and
      regulatory cytokines determined in blood sera by solid-phase EIA method by using
      Biosource (Austria) test-systems at the beginning of the study and after the
      therapy. RESULTS: In patients with exudative erythema multiforme Immunovac-VP-4
      therapy facilitated a significant (p < 0.05) increase of serum IFN-gamma level,
      insignificant (p > 0.05) increase of IL-1beta and decrease of IL-17. Whereas
      cagocel lead to an increase of IL-4 (p > 0.05), IL-2, IFN-gamma (p < 0.05) and
      decrease of TGF-beta and IL-12 (p < 0.05). At the same time basic therapy
      facilitated a significant increase of IL-5 and decrease of IL-6, IL-12, IFN
      gamma. CONCLUSION: Immunovac-VP-4 facilitates the increase of secretion of IFN
      gamma, IL-1beta against the background of TGF-beta that facilitates normalization
      of cooperation of cells in immune response including against viral infections,
      and thereby influencing the trigger factor in EME patients.

PMID- 24738293
TI  - [Real-time pcr procedure for determination of Streptococcus pneumoniae
      serotypes].
AB  - AIM: Development and application of real-time PCR (RT-PCR) procedure for
      determination of Streptococcus pneumoniae serotypes. MATERIALS AND METHODS: S.
      pneumoniae cps-locus wzx, wzy, wzz, wcwV and galU genes were chosen as PCR
      targets to select serotype-specific oligonucleotide primers and fluorescent
      labeled probes. 89 samples of cerebrospinal fluid (CSF) obtained in 2007 - 2010
      from patients with pneumococcal meningitis diagnosis undergoing therapy in the
      Infectious Clinical Hospital No. 2, Moscow, were studied with the aim of testing
      the possibility of practical use of RT-PCR. RESULTS: Primers and probes were
      selected for the determination of 16 vaccine and/or frequently encountered
      serotypes distributed among 4 reaction mixtures also including a pair of primers
      and a probe for cpsA gene detection that is present in all the capsule
      pneumococci (internal control). The procedure was tested on a collection of 108
      pneumococci strains gathered in Research Institute of Antimicrobial Therapy and
      serotyped earlier by specific PCR with electrophoretic detection and
      serologically by using Pneumotest-Latex kit. The sensitivity and specificity of
      the RT-PCR was 100%. RT-PCR procedure allowed to determine pneumococcus serotype
      in 79% of CSF clinical samples containing S. pneumoniae DNA. Serotype 3 and 23F
      were detected most frequently (13%, each). CONCLUSION: RT-PCR application does
      not assume causative agent seeding stage, significantly reduces analysis
      execution time and increases sensitivity of the study. The developed procedure
      will allow to begin addressing the important problem--clarification of spectra
      and frequency of occurrence of pneumococci serotypes circulating on the territory
      of Russia.

PMID- 24738294
TI  - [Anti-herpetic effect of photodynamic action in an in vitro experiment].
AB  - AIM: Evaluation of photodynamic therapy (PDT) in vitro antiviral effect directly
      on the herpes simplex virus (HSV) as well as on virus infected cells. MATERIALS
      AND METHODS: HSV infected Vero cell culture; HSV-1 (VR-3 strain) and HSV-2 (MS
      strain) were used. Fotoditazin preparation (chlorin E6 derivative) was used as a
      photosensitizer. AFS physiotherapy apparatus was used for laser irradiation.
      Experiment variants: study of direct and mediated photodynamic effect on virus
      containing fluid (HSV-1 and HSV-2) and on non-infected cell culture; evaluation
      of anti-herpetic effect of PDT and study of the effect on the newly produced HSV
      1 progeny were carried out within the developed experiment scheme. RESULTS: A
      scheme of experiment conduction for study of mediated photodynamic effect of HSV
      was developed. A significant reduction of virus titers for more than 2 orders of
      magnitude (100-1000 times) was detected. Optimal concentration of photosensitizer
      and laser irradiation dose that results in reduction of HSV-1 titers by 1000 and
      more times (1.5 - 2.5 orders of magnitude) and reduction of HSV-2 titers by 10
      and more times (1.5 order of magnitude) were determined. CONCLUSION: The data
      obtained will help selection of adequate scheme of PDT conduction for patients
      with recurrent herpes virus infection including patients with recurrent
      miscarriage.

PMID- 24738295
TI  - [Quantitative determination of HBsAg in blood sera and hepatitis B virus
      covalently closed circular DNA in liver tissue as markers of chronic viral
      hepatitis B activity].
AB  - AIM: Quantitative evaluation of HBV covalently closed circular DNA (cccDNA)
      content in liver tissue of patients with moderately active CHBV course compared
      with inactive HBsAg carriers as well as establishment of a possible link between
      HBV cccDNA in liver cells and HBsAg level in blood sera in these groups of
      patients. MATERIALS AND METHODS: Patients (n = 34) with CHBV diagnosis were
      examined for levels ofALT, HBsAg (qualitatively and quantitatively), anti-HBcor
      IgG, anti-HBe IgG, anti-HCV IgG+IgM, anti-HDV IgG+IgM, HBV DNA in qualitative and
      quantitative variant. Liver biopsy was carried out in all the patients. HBV DNA
      was determined in liver tissue by Pollicino T. et al. (2004). RESULTS: Based on
      HBV DNA PCR, the patients were allocated to a group of inactive HBsAg carriers (n
      = 16) and CHBV (n = 18) of moderate activity. Viral load in CHBV patients had a
      mean of 540 +/- 230 IU/ml. ALT level in carriers was comparatively lower than in
      patients with CHBV. HBsAg level in blood of inactive carriers was significantly
      lower, 940 +/- 259 IU/ml against 2559 +/- 982 IU/ml in patients with CHBV (p <
      0.05). The quantity of cccDNA per 1 cell in inactive HBsAg carriers--0.15 +/-
      0.14, and in patients group of CHBV with moderate activity--1.71 +/- 1.32 (p =
      0.034). CONCLUSION: The method of quantitative determination of HBV cccDNA in
      liver tissue of patients was worked out. Differences in quantitative content of
      HBsAg in blood sera of inactive carriers and CHBV patients with moderate activity
      reflect changes in the extent of hepatocyte infection by HBV.

PMID- 24738296
TI  - [Influence of antibiotics on formation of microecology in premature children with
      low and extremely low body weight at birth].
AB  - AIM: Study the influence of antibiotic therapy on the formation of main biotope
      microflora nasopharynx, large intestine, urinary system) of the premature child
      organism weighing less than 500 g at birth in hospital. MATERIALS AND METHODS:
      Bacteriological study of upper respiratory tract discharge, urine, large
      intestine contents in 58 premature children during admission and discharge from
      newborn and premature children pathology department was carried out. Factor
      analysis method was applied to construct factor models of antibiotics influence
      on main biotope microbiocenosis formation. RESULTS: Deficiency of obligatory
      normal flora members in all the 3 biotopes was noted in all the children during
      admission to the department. Colonization of all the biotopes by obligatory
      members was noted by discharge, however the parameters do not reach age norm.
      Antibiotics therapy is the main factor, in all the biotopes opportunistic and
      pathogenic microorganisms prevail. CONCLUSION: The formation of main biotope
      microbiocenoses does not occur and carriage of pathogenic and opportunistic
      microorganisms is noted in premature children receiving massive antibiotic
      therapy.

PMID- 24738297
TI  - [Disinfectology as molecular-epidemiologic direction of infection control].
AB  - Specific aims of environment biologic pathogen control by applying special
      disinfectologic means and technologies are formulated. The main components of
      disinfectologic process are examined: molecular-biologic properties of targets-
      their sensitivity (resistance) to biocidal agents; biocidal molecular-chemical
      properties of disinfection means; toxicological properties of the latter by their
      effect on human organism as the object of epidemiologic protection. Perspectives
      of improvement of disinfectologic technologies by using composition potential of
      different actively operating molecular substances are discussed.

PMID- 24738298
TI  - [Experience of Olympic host-countries in procuring protection from a biological
      threat].
AB  - Experience of Olympic Games host-countries in procuring protection from a
      biological threat is examined. Based on analysis of measures directed at
      improvement of systems of epidemiologic control and bioterrorism counteraction at
      London Olympics (2012), recommendations are given on the main directions of
      organizational, prophylactic and anti-epidemic activities during mass events.

PMID- 24738299
TI  - [Operation preparedness of specialized anti-epidemic brigades during mass
      events].
AB  - Operation experience of specialized anti-epidemic brigades (SAEB) for the support
      of sanitary-epidemiologic welfare during various emergencies is presented. The
      order of functioning and SAEB objectives during mass events is examined. Analysis
      of exercise of Stavropol Institute of Plague Control SAEB was carried out,
      proposals for augmentation of SAEB equipment table by instruments and reagents
      for indication and genotyping of pathogen strains are examined.

PMID- 24738300
TI  - [Post of atmospheric air control for the presence of pathogenic biological agents
      and its significance in the system of biological threat counteraction].
AB  - Contemporary experience of organization of atmospheric air monitoring for the
      presence of pathogenic biological agents (PBA) is generalized in the article.
      Proposals for the use of posts of atmospheric air control during mass events are
      presented. Issues of equipping the instrument base for air sampling and PBA
      detection are examined.

PMID- 24738301
TI  - [Improvement of epidemiologic control of infectious diseases by using
      geoinformational systems].
AB  - Problems of the perspective of geoinformational systems (GIS) use for improvement
      of epidemiologic control of infectious diseases including during mass events are
      examined. A scheme of creation of the decision making support system (DMSS) is
      proposed, the system is based on GIS, has general primary data and analytical
      prognostic tool base including subsystems: real-time primary information intake,
      information analysis, epizootic and epidemic activity prognosis on the certain
      territories and the federal level. Specialized personnel training, creation of
      infrastructure for DMSS functioning in primary Federal Service of Surveillance
      for Protection of Consumers Rights and Human Welfare units are designated as
      priority tasks.

PMID- 24738302
TI  - [Adjuvants in modern medicine and veterinary].
AB  - The review is dedicated to immunologic adjuvants--various natural and synthetics
      substances that are added to vaccines for stimulation of specific immune
      response, but they do not induce specific response themselves. Critically
      important is the selection of the correct adjuvants, for which mechanisms of
      effect on immune system are studied the most. The majority of these mechanisms as
      well as physical-chemical and biological features of modern adjuvants are
      analyzed in the review. The problem of safety of adjuvants, types of immune
      response induced by adjuvants of various nature, excipients that are being
      verified or already in use in modern medicine and veterinary are also examined.

PMID- 24738303
TI  - [Live attenuated and inactivated influenza vaccines: data from direct comparative
      studies].
AB  - Comparative evaluation of live attenuated and inactivated influenza vaccines
      based on data from direct comparative studies is necessary for ensuring the most
      effective and safe vaccination against influenza. Analysis of direct comparative
      preclinical and clinical studies of inactivated and live cold-adapted (ca)
      influenza vaccines showed that published data are inconsistent and limited for
      some population groups. Live ca vaccines may be promising as an alternative or
      addition to inactivated vaccines especially for mass vaccination against
      influenza in children as well as in the elderly when combined with inactivated
      vaccines. Further studies of inactivated and live ca influenza vaccines in direct
      comparative studies that control the administration route and vaccine strain
      production as well as development and confirmation of objective criteria of live
      attenuated influenza vaccine effectiveness evaluation are necessary.

PMID- 24738304
TI  - [Problems on the diagnosis of unilateral nasal and sinus lesions].

PMID- 24738305
TI  - [Short-term efficacy of standardized medication offer chronic rhinosinusitis].
AB  - OBJECTIVE: To evaluate the efficacy of standardized medication for patients with
      chronic rhinosinusitis. METHOD: According to the diagnosis and treatment
      guidelines on chronic rhinosinusitis formulated in 2008, by means of prospective
      study, we studied 54 patients suffering from chronic rhinosinusitis treated with
      standardized medication including, a combination of local intranasaI
      corticosteroids, macrolides, mucus discharging agent and nasal irrigation
      treatment and followed up for 3 months. Visual analogue scale (VAS), sino nasal
      outcome test-20 Chinese version scales (SNOT-20 CV), Lund-Mackay CT and Lund
      Kennedy endoscopy methods were employed to conduct the subjective and objective
      assessment and comprehensively evaluate the clinical efficacy before and after
      treatment. RESULT: (1) After three months of standardized medication, the
      patients' total scores of VAS, SNOT-20 CV, CT and endoscopy were improved
      significantly compared with those before-treatment (P < 0.01 for all these
      scoring systems). (2) There was statistically significant difference between the
      clinical efficacies of chronic rhinosinusitis patients with and without nasal
      polyps groups (P < 0.01). After 3 months of standardized medication, the
      effective rates of the CRSwNP group evaluated by subjective assessment and CT
      evaluation were 66.7% and 94.4% respectively, while those of the CRSsNP groups
      were 91.7% and 97.2% respectively. (3) Betwecn CRSwNP and CRSsNP groups, there
      was no significant difference in the improvement rate or inefficiency rate in
      subjective assessment except for the cure rate, while there were significant
      differences in both cure rate and improvement rate in CT evaluation. (4) The CRS
      patients' self-testing-based questionnaires results showed positive correlation
      with objective assessments. CONCLUSION: The standardized medication with
      combination of intranasal local glucocorticoid, macrolides (14-membered ring),
      the mucus discharging agent and nasal irrigation on CRS was effective.

PMID- 24738306
TI  - [Prospective efficacy of chronic sinusitis lost to short-term follow up after
      nasal endoscopic surgery].
AB  - OBJECTIVE: To investigate the prospective efficacy of chronic sinusitis lost to
      short-term follow up after nasal endoscopic surgery and the influential factors.
      METHOD: Prospective efficacy of 153 chronic sinusitis (CRS) was evaluated . All
      cases were treated by nasal endoscopic surgery at least 1 year ago but lost to
      follow up within 3 months after surgery. The clinical data of 153 patients were
      analyzed, including gender, age, educational level, course of the disease,
      smoking and drinking history, early surgery history, allergic rhinitis (AR)
      history, nasal polyps, visual analogue scale (VAS) score, nasal endoscopy score,
      CT examination score, the endoscopic experience of surgeons, medication of
      intranasal glucocorticoid and nasal irrigation after surgery. Multifactor
      logistic regression analysis were used to analyze the data. RESULT: Among 153
      patient, the symptoms of 32 cases (20.9%) were completely control, while those of
      74 cases (48.4% ) were partially control, and the symptoms of 47 cases (30.7%)
      were not controlled. The curative effect were better for CRS without nasal
      polyps, AR or early surgery history, with CT examination score < or = 5, operated
      by surgeons with experience of endoscopy surgery for more than 5 years. and
      treated with intranasal glucocorticoid for more than -1 weeks after surgery.
      CONCLUSION: Postsurgery follow-up should be paid more attention to in treatment
      of CRS. Plans of follow up should be adjusted to patients condition. Treatment of
      postoperative sinus cavity should be minimized when the lesion is slight and
      operated properly.

PMID- 24738307
TI  - [Correlation between subjective evaluation and objective examination in patient
      with fungal rhino-sinusitis].
AB  - OBJECTIVE: The study was to evaluate the quality of life in patients with fungal
      rhino-sinusitis(FRS) and to investigate the relationship between different
      subjective tests.objective measures and that between subjective tests and
      objective measures. METHOD: Quantitative data of 18 preoperative recruits with
      FRS were collected by using sino-nasal outcome test-20 (SNOT-20) and then the
      SNOT-20 items were categorized into five domains, a visual analogue scale (VAS).
      Lund-Kennedy endoscopy staging system and the Lund-Mackay CT staging system.
      Correlation among these data was analyzed. RESULT: The six highest score items in
      SNOT-20 were Facial pain/pressure, Thick nasal discharge, Need to blow nose,
      Sneezing, Fatigue, and Frustrated/restless/irritable. The total SNOT-20 score was
      not correlated with the other objective or subjective tests(P > 0.05). However,
      there was significant correlation between SNOT-20 nasal symptom domain and Lund
      Mackay T score( r = 0.605, P < 0.01), as well as between SNOT-20 sleep related
      symptom domain and VAS (r = 0.605, P = 0.008). Significant correlation was found
      between the Lund-Mackay CT staging and the VAS (r = 0.6150, P < 0.01), as well as
      between the Lund-Mackay CT staging and the Lund-Kennedy endoscopy staging (r =
      0.5001 P < 0.05). There was no significant correlation between Lund Kennedy
      endoscopy staging and the patient-based questionnaires (P > 0.05). CONCLUSION:
      The objective measures were correlated well with each other and CT staging had
      significant correlation with the SNOT-20 nasal symptom domain and VAS. There was
      also significant correlation between SNOT-20 sleep related symptom domain and
      VAS.

PMID- 24738308
TI  - [Association analysis of IL-23R polymorphisms in allergic rhinitis].
AB  - OBJECTIVE: Polymorphism of interleukin-23 receptor (IL-23R) gene was found being
      related with the susceptibility to several immune-related diseases. For the
      terminal differentiation of IL-17-producing effecter T-helper cells in vivo, the
      IL-23R gene is very important. As proved recently, Th17 cells might have a great
      influence to the pathogenesis of allergic airways disease. Our intention was paid
      to find any association between the polymorphisms in the IL-23R gene and allergic
      rhinitis(AR) in Chinese population. METHOD: A group of patients was involved in a
      case-control comparison, consisted of 239 AR patients and 271 control Chinese
      subjects. The study claimed to take some blood samples for DNA extraction and
      select 3 single-nucleotide polymorphisms in IL-23R individually genotyped by the
      PCR-RFLP method. RESULT: Comparison with the controls, a great growing prevalence
      of the homozygous rs7517847 GG genotype and G allele appeared in AR patients (P <
      0.05, respectively). Besides, a great increased frequency of the GGA haplotypes
      was presented in AR patients in comparison with the controls (P < 0.05).
      CONCLUSION: The results demonstrated a important association pattern between
      polymorphisms in IL-23R and AR in Chinese population. Between rs7517847 in an SNP
      of IL-23R and AR, a great association was identified.

PMID- 24738309
TI  - [The influence of sublingual immunotherapy on Th2 type immunoreaction in patients
      with allergic rhinitis].
AB  - OBJECTIVE: To explore the influence of sublingual immunotherapy on Th2 type
      immunoreaction in patients with allergic rhinitis within 12 months' treatment.
      METHOD: Forty three patients with allergic rhinitis were followed-up within 12
      months after receiving sublingual immunotherapy. The changes of clinic symptoms
      and immunoreaction were analyzed. VAS score was applied to evaluate the efficacy
      of clinic treatment. TIgE and sIgE in serum were tested to evaluate the systemic
      immunoreaction. Eosinophil counting in nasal discharge was applied to evaluate
      the local nasal mucosa immunoreaction. RESULT: VAS scores were decreased
      significantly one month after the starting point of treatment, companied by the
      decrease of EOS count in nasal discharge (P < 0.05). The changes of TIgE and sIgE
      in serum within 12 months of sublingual immunotherapy were not significant (P <
      0.05). The levels of IL-4 and IL-13 in nasal lavage were decreased significantly
      after 12 months' treatment. CONCLUSION: The bias of Th2 type immunoreaction
      existed in nasal mucosa immune system in patients with allergic rhinitis could
      been rectified partially after receiving sublingual immunotherapy for 12 months,
      but the significant changes were not observed in systemic immune system.

PMID- 24738310
TI  - [17 cases of mucosal antral cyst with main symptoms of eye pain].
AB  - OBJECTIVE: To draw the attention to mucosal antral cyst, thus reduce the
      probability of missed diagnosis and missed treatment by retrospectively analyzing
      17 cases of eye pain patients with no obvious nasal symptoms in our department
      from January 2003 to September 2011. METHOD: All patients were performed
      ophthalmologic examination including eye position, eyesight, refraction, visual
      field, intraocular pressure and fundus examination, and the results showed that
      all of them had no eye disease. After excluding the deviation of nasal septum,
      concha bullosa and Haller gas room, CT scanning of paranasal sinus showed the
      maxillary sinus cyst. The patients were operated by nasal endoscope through joint
      path of middle meatus or inferior meatus and given antibiotics after operation.
      The nasal cavity packing was removed 24 hours postoperatively and the patients
      were discharged from hospital a week later. All the patients continued using
      intranasal corticosteroids and were followed up for half a year to observe
      whether the eye pain disappeared or recurred, when various processing was given
      to the surgical cavity with the help of nasal endoscope. RESULT: Among the 17
      cases, 14 cases of eye pain disappeared after the operation, and the remaining 3
      patients got symptomatic relief without recurrence during the follow-up period.
      CONCLUSION: Mucosal antral cyst can cause eye pain. After excluding eye disease,
      once we diagnosed patients for mucosal antral cyst and the routine application of
      corticosteroids treatment was proved to be invalid, we should take operation
      treatment as early as possible, regardless of the size and location of the cysts.

PMID- 24738311
TI  - [Epidemiological investigation and related risk factors analysis of allergic
      rhinitis in primary and middle school students in Changsha].
AB  - OBJECTIVE: To analyze the epidemiological characteristics and related risk
      factors of allergic rhinitis in primary and middle school students in Changsha so
      that to provide the scientific basis for the disease control and intervention.
      METHOD: From June 2011 to April 2012, we randomly chose primary and middle school
      students aged from 10 to 17 years old in Changsha as our research objects.
      Through stratified sampling and cluster sampling, we carried out epidemiological
      investigation using questionnaire investigation, physical examination and skin
      prick test. After statistical analysis of the data,we explored the related risk
      factors. RESULT: (1) 7,023 copies of questionnaire were sent out and 6,407 copies
      of valid questionnaire were received in the stratified sampling survey. The
      prevalence of complaining about having got allergic rhinitis is 44.6% while the
      real rates is 20.5%; (2) 814 research objects were investigated in cluster
      sampling survey. The result of the incidence of allergic rhinitis is 26.3%, and
      the prevalence of allergic rhinitis is 17.2%. Analysis of Visual Analog Scale
      Questionnaire showed significant influence of allergic rhinitis on students
      character, memory, sleep quality, etc. CONCLUSION: The prevalence of allergic
      rhinitis in primary and middle school students aged at 10-17 years old in
      Changsha is 17%-20%. The occurrence and development of allergic rhinitis is
      related to environment, genetic background and living habits. Allergic rhinitis
      influenced the students' character, memory and sleep quality significantly.

PMID- 24738312
TI  - [Skin prick test of inhalative allergens for patients with allergic rhinitis in
      Yichang].
AB  - OBJECTIVE: To investigate the allergens in patients with allergic rhinitis in
      Yichang, so that to find common allergens of Yichang and to provide statistic
      basis for a reasonable prevention and treatment to allergic rhinitis. METHOD:
      1,979 patients with allergic rhinitis in Yichang were detected for allergens by
      skin prick test and the distribution of positive rates to inhaled allergens was
      compared between different genders and ages. RESULT: 1,545 (78.1%) of 1,979
      suspected allergic rhinitis patients presented positive reaction. The positive
      rate in male was significantly higher than in female, and that in juvenile group
      was significantly higher than in adults. Among positive cases in inhalation
      group, the most common allergen was flour mite (80.4%), followed by house dust
      mite (64.9%), cockroach (13.3%) and artemisia pollen (8.2%). CONCLUSION: The
      study shows that the flour mite and house dust mite are the most common inhaled
      allergens causing allergic rhinitis in Yichang. We should pay more attention to
      the prevention and treatment for the juvenile patients.

PMID- 24738313
TI  - [Preliminary analysis of SPT tests on 5,843 allergic rhinitis patients from south
      Shanghai area].
AB  - OBJECTIVE: To explore the distribution of allergen tested by skin prick test
      (SPT) in about 5,843 allergic rhinitis patients in south Shanghai. METHOD: SPT
      test was conducted in 5,843 allergic rhinitis patients who came to our clinic
      from January 2007 to August 2012. The result was analyzed by age, sex and year.
      RESULT: The top three allergens by percentage are dermatophagoides pteronyssinus,
      dermatophagoides culinae and fungus among 15 common allergens. Incidence rate
      between male and female in each year had statistical significance, both of which
      showed no increasing trend with year. Incidence rates among different age groups
      aging from 6 to 17 years' old had no statistically significant difference, but
      statistically significant difference among different age groups existed in other
      age groups. Incidence rate showed increasing trend with year in age group of 40
      65, which was not observed in other groups. The incidence rate showed decreasing
      trend with age in male and female, while the incidence rate in male was always
      higher than female. CONCLUSION: In south Shanghai, primary allergens causing
      allergic rhinitis are dermatophagoides pteronyssinus, dermatophagoides culinae
      and fungus. Statistically significant difference about allergic rhinitis existed
      in age and sex. SPT has important significance in diagnosis of allergens.

PMID- 24738314
TI  - [The expression and significance of trefoil factor 3 and SDF-1/CXCR4 biological
      axis in papillary thyroid carcinoma].
AB  - OBJECTIVE: To study the expression of trefoil factor 3 (TFF3)with stromal cell
      derived factor (SDF-1) and its receptor (CXCR4) in papillary thyroid
      carcinoma(PTC), and investigate the function of TFF3, SDF-1/ CXCR4 and the
      relationship among them during the tumor genesis,development and outcome of PTC.
      METHOD: Detecting the expression of TFF3 and SDF-1/CXCR4 by immunohistochemical
      method (SP) in 92 cases of PTC and para-carcinoma tissue. Semiquantitative
      analysis of the results of immunohistochemistry was conducted by image analysis
      software. RESULT: (1) TFF3 protein was expressed in the cytoplasm of cancer
      cells,while TFF3 was negative or weakly positive in follicular cells of para
      carcinoma tissue. The positive expression rate of TFF3 was 92.39%, of which the
      strong positive rate of clinical stage III-IV accounted for 71.79% (42/59) and
      that of clinical stage I-II was 33.33% (11/33) (P < 0.01). The positive rate of
      TFF3 was significantly higher in the cases with lymph node metastasis than those
      without lymph node metastasis (100.00% vs 86.27%, P < 0.05). The AOD value of
      TFF3 was higher in PTC than in para-carcinoma tissue, that in cases with lymph
      node metastasis was higher than those without lymph node metastasis, and that in
      stage III-IV was higher than those in I-II (P < 0.05 or P < 0.05). (2) There was
      high expression of SDF-1 in the cytoplasm of malignant tissues. The para
      carcinoma tissue was weakly positive or negative to SDF 1 and metastatic lymph
      nodes was weakly positive to SDF 1. The positive rates and AOD values of SDF-1
      protein were similar to those of TFF3 in PTC,that is to say the positive rate and
      AOD values were higher in PTC than in para-carcinoma tissue, those in cases with
      lymph node metastasis were higher than those without lymph node metastasis, those
      in stage III-IV were higher than those in I-II, and those in patients older than
      45 years old was obviously higher than those in patients under 45 years old (P <
      0.05 or P < 0.01); CXCR4 was also mainly expressed in cytoplasm with few
      expression in nuclei, while negative or weakly positive in para-carcinoma. The
      positive rate and AOD values of CXCR4 in PTC were similar to SDF-1, meaning that
      they were higher in PTC than in para-carcinoma tissue and associated with the
      clinical stage, lymph node metastasis and age (P < 0.05 or P < 0.01). (3) There
      was positive relationship between TFF3 and SDF-1 as well as between SDF-1 and
      CXCR4 in PTC (r = 0.971, P < 0.01). CONCLUSION: The high expression of TFF3, SDF
      1 and CXCR4 in PTC are correlated with carcinogenesis and progression, and may
      play a significant role in evaluating the malignancy degree and progression of
      PTC.

PMID- 24738315
TI  - [The treatment of trigeminal neuralgia by resecting maxillary nerve and
      infraorbital nerve under the endoscopy at the pterygopalatofossa through approach
      to the maxillary sinus].
AB  - OBJECTIVE: This paper presents a method for treating maxillary neuralgia, the
      second division of trigeminal nerve. METHOD: One hundred and thirty six cases
      with 136 trigeminal neuralgia were treated from 2004 to 2011. All patients were
      treated with endoscopic surgery at the pterygopalatofossa through approach to the
      maxillary sinus for resecting maxillary nerve and infraorbital nerve. RESULT: One
      hundred and eighteen patients were relieved after operation and no recurrence of
      neuralgia was occurred after 2 to 8 years of follow-up. CONCLUSION: This method
      had the advantages of avoiding to operate craniotomy with no complications, which
      was performed easily with valid efficacy.

PMID- 24738316
TI  - [The application of micro-sensitive mattress type sleep monitor in the diagnosis
      of OSAHS in children].
AB  - OBJECTIVE: To investigate the result of child-type micro-sensitive mattress sleep
      monitor on obstructive sleep apnea-hypopnea syndrome in children. METHOD: The PSG
      and child-type micro-sensitive mattress sleep monitor were synchronously
      performed on 58 cases of children with OSAHS. The breathing and sleep metrics
      were compared. RESULT: By PSG monitoring, 41 cases were diagnosed as mild OSAHS,
      14 cases were moderate and 3 cases were severe. The results of mattress system
      monitoring showed mild OSAHS in 37 cases, 16 cases of moderate and severe OSAHS
      in 5 cases. Seven patients diagnosed as mild OSAHS monitored by PSG were
      classified as moderate by mattress system monitoring; three cases diagnosed as
      mild OSAHS by mattress system monitoring system were diagnosed as moderate by
      PSG. Among 14 cases of children diagnosed as moderate by PSG, three cases were
      diagnosed as mild by mattress system monitor and two cases as severe. Children
      diagnosed as severe by PSG got the same result by mattress system monitor. Two
      kinds of sleep monitoring methods were compared and there were no statistically
      significant difference in AHI (t = 2.316, P > 0.05), deep and shallow sleep
      constituent ratio (t = 2.280, t = 2.388, PF > 0.05). while there was significant
      difference in REM period Sleep constituent ratio (t = 3.135, P < 0.01).
      CONCLUSION: Child-type micro-sensitive mattress is in good agreement with the PSG
      for diagnosing OSAHS in children, which can be used as a monitoring method in
      clinical work.

PMID- 24738317
TI  - [Efficacy of nasal packing, septal suture technique and vacuum sealing drainage
      after nasal septum surgery].
AB  - OBJECTIVE: The objective of this study was to evaluate the effect of nasal
      packing, septal suture technique and vacuum sealing drainage (VSD) after
      septoplasty. METHOD: Ninety patients of nasal septal deviation in Combination
      with outfracture of the inferior turbinates who had received septoplasty were
      selected in this study. The patients were allocated into three groups, with
      thirty in each: for packing group, marcel materials were used for nasal packing
      after septoplasty; for suturing group, septal suture technique was performed
      after septoplasty; for VSD group, one drainage tube was used for negative
      pressure sucking after septoplasty without nasal packing. Postoperative signs and
      symptoms were compared between three groups. The comfort degree assessment
      included headache and nasal obstruction were evaluated by using visual analogue
      scale (VAS) at the 12th hour and 24 hour after operation. The edema in nasal
      cavity, hemorrhage. abscess,adhesive and healing rates after operation were
      compared among three groups. RESULT: The VAS score of headache and nasal
      obstruction and the severity of patient's conditions were significantly less in
      septal suture group and VSD group than that in packing group at the 12th and 24th
      hour after operation. The mucosa edema of nasal cavity was significantly slighter
      in septal suture group and VSD group than that in packing group at the third day
      after operation. The healing rates and number of complications are better in
      septal suture group and VSD group than those in packing group at the 7th day
      after operation. There were no hemorrhage or abscess in VSD group. CONCLUSION:
      Septal suture technique and VSD after septoplasty can significantly relieve the
      distress of patients and reduce the healing time of mucosa in nasal cavity
      without increasing the risk of complications.

PMID- 24738318
TI  - [Immunoelectron microscopic analysis of neurotoxic effect of glutamate in the
      vestibular end organs during ischemia].

PMID- 24738319
TI  - [Absorbable shanching satin rb-bFGF prepreg sheet and expansion hemostatic sponge
      together to cure epistaxis with blood disease].
AB  - OBJECTIVE: This study investigated the effects and Numerical Rating Pain Scale
      (NRS) of using absorbable shanching satin rb-bFGF prepreg sheet and expansion
      hemostatic sponge together nasal packing in the control of epistaxis with blood
      disease, and compared it with traditional vaseline gauze. METHOD: Ninety-six
      blood disease patient with epistaxis were enrolled between January 2009 and
      February 2011, they were divided into two groups at random, and differently
      treated with absorbable shanching satin rb-bFGF prepreg sheet and the vaseline
      gauze nasal packing for haemostasis. Then haemostasis efficacy,the hemorrhage
      rate after nasal packing removed and host response, such as nasal pain and
      headache, which evaluated pain degrees against NRS, were all observed. RESULT:
      There was no significant difference between the two groups of the haemostatic
      effect. But the hemorrhage rate of treatment group was obviously lower than that
      of the control group after paching,in addition, host responses, such as nasal
      pain and headache, remarkably better than the control group, the difference had
      statistical significance. CONCLUSION: It is indicate that absorbable shanching
      satin rb-bFGF prepreg sheet presents reliable hemostasis effect, good
      biocompatibility and compliance; the pain and headache caused by packing are
      superior to vaseline gauze. Moreover, this method avoids the direct touch of
      vaseline gauze with nasal mucosal wound, and reduce hemorrhage after packing.
      Absorbable shanching satin rb-bFGF prepreg sheet and expansion hemostatic sponge
      together is better to select the nasal packing material for blood disease patient
      with epistaxis.

PMID- 24738320
TI  - [The expression of tumor related macrophages and matrix solution element in
      laryngeal squamous carcinoma tissue and the relationship with tumor microvascular
      density].
AB  - OBJECTIVE: To study the expression of CD68 antibody marked tumor associated
      macrophage TAMs and matrix solution element MMP-7 in laryngeal squamous carcinoma
      tissue and the relationship with clinicopathological parameters, so that to
      explore the relationship between the expression of the two molecular markers and
      laryngeal cancer tissue microvascular density (MVD). METHOD: Immunohistochemical
      method was employed to detect the expression of CD68 and MMP-7 in 65 cases
      (laryngeal squamous carcinoma tissue in 45 cases; peritumoral nontumor tissue in
      20 cases) and CD 34 antibody marked MVD expression. RESULT: CD68 positive rate in
      squamous carcinoma tissue (82.2%, 37/45) is obviously higher than that in the
      peritumoral tissue (15%, 3/20) (P < 0.05), and MMP-7 positive rate in squamous
      carcinoma tissue is significantly different from that in peritumoral tissue
      (71.1%; 25%) (P < 0.05). The expression rate of CD34-MVD in laryngeal squamous
      carcinoma tissue( 26.52 +/- 6.36 )is higher than that in peritumoral tissue
      (12.23 +/- 4.01) (P < 0.05). In lymph node metastasis group, the positive
      expression rates of CD68 and MMP-7 are higher than those in the group without
      lymph node metastasis. MMP-7 showed no correlation with cancer stage, and CD68
      was related with cancer stage; CD68, MMP-7 and CD34- MVD have positive
      correlation. CONCLUSION: The high level of expression of TAMs and MMP-7 in
      laryngeal cancer tissue and the positive correlation with MVD illustrate that
      both of the markers play important roles in promoting laryngeal squamous
      carcinoma tissue metastasis and angiogenesis, which can be used as important
      markers to evaluate the invasion and metastasis of laryngeal cancer.

PMID- 24738321
TI  - [Analysis of symptoms in patients with allergic rhinitis].

PMID- 24738322
TI  - [Rescue of upper airway obstruction after otolaryngological surgery under general
      anesthesia].

PMID- 24738323
TI  - [One case of primary malignant lymphoma of the maxillary sinus].
AB  - Malignant lymphoma of the maxillary sinus is very rare. A case of diffuse large B
      cell lymphoma (DLBCL) of the left maxillary sinus is presented here. A 59-year
      old man came to our hospital complaining of swelling under the left lower eyelid
      without any other symptoms. Imaging examination including CT and MRI detected a
      tumor in the left maxillary sinus. The tumor was invasive into left orbit. The
      biopsy revealed a diffuse large B-cell lymphoma. The tumor cells were positive to
      CD20, CD79a, CD45. In conclusion, a very rare case of DLBCL of the maxillary
      sinus was reported.

PMID- 24738324
TI  - [One case of epistaxis and alcohol withdrawal syndrome].
AB  - The patient with long history of alcohol was admitted because of intermittent
      right nasal bleeding for two days,and treated by nasal packing. After 3 days,the
      patient exhibited auditory hallucinations and immediately showed rage, mania,
      sweating and fever. CT examination showed calcification in the right frontal
      lobe, brain atrophy and sinusitis. DIAGNOSIS: epistaxis and alcohol withdrawal
      syndrome, deviated septum, sinusitis.

PMID- 24738325
TI  - [One case of auricle cartilage calcification].
AB  - The patient complained of painless mass in the right ear for 3 months. The
      ipsilateral ear was 1/2 thicker than contralateral one and felt stiff without
      elasticity. There was limited eminence in cavum conchae about 1 mm in height and
      about 6 mm x 10 mm in size with clear boundary. which felt hard without
      tenderness. X-ray showed a long oval nodular calcification with clear but
      irregular boundary in cavum conchae under the right auricle, the size of which
      was about 4 mm x 7 mm. The patient was diagnosed right auricle cartilage
      calcification.

PMID- 24738326
TI  - [A review: the role of antimicrobial peptide LL-37 in chronic sinusitis].
AB  - The purpose of this review is to explain the function of LL-37 in the
      pathogenesis of chronic sinusitis. LL-37 is the only human cathelicidin
      identified so far. LL-37 is an integral part of the innate immune,the role of
      which in chronic sinusitis is attracting more and more s attention.

PMID- 24738327
TI  - Enhancing curcumin anticancer efficacy through di-block copolymer micelle
      encapsulation.
AB  - We report herein the development of a novel aqueous formulation and improved
      antitumor activity for curcumin by encapsulating it into a biocompatible and
      biodegradable poly(L-lactic acid) based poly(anhydride-ester)-b-poly(ethylene
      glycol) (PAE-b-PEG) micelle. The resulting curcumin loaded micelles were
      completely water-dispersible, overcoming the problem of poor water solubility
      that limited its efficacy and bioavailability. In vitro cellular studies revealed
      that the curcumin-loaded micelles were taken up mainly via endocytosis route and
      exhibited higher cytotoxicities toward model cancer cell lines (HeLa and EMT6)
      than free curcumin. An in vivo biodistribution study revealed that the curcumin
      loaded micelles displayed significantly enhanced accumulation inside the tumor of
      EMT6 breast tumor-bearing mice. More impressively, the curcumin-loaded micelles
      showed stronger antitumor activity, higher anti-angiogenesis effects and induced
      apoptosis on the EMT6 breast tumor model bearing mice than free curcumin.
      Furthermore, the curcumin-loaded micelles showed no significant toxicity towards
      hemotological system, major organs or tissues in mice. Combined with a high
      antitumor activity and low toxic side-effects, the curcumin-loaded micelles
      developed here thus appear to be a highly attractive nanomedicine for effective,
      targeted cancer therapy.

PMID- 24738328
TI  - An in vitro study of a titanium surface modified by simvastatin-loaded titania
      nanotubes-micelles.
AB  - To develop an optimized local delivery system of simvastatin (SV) with improved
      osseointegration of titanium (Ti) implants, SV-loaded poly(ethylene glycol)
      poly(epsilon-caprolactone) (PECL) micelles (80 nm in diameter) were loaded in
      titania nanotube (TNT) arrays (80-100 nm in diameter and 400 nm in length) that
      were fabricated by anodizing Ti sheets. An in vitro release experiment was
      performed and revealed that TNTs and micelles can jointly provide a sustained
      release of SV, and that TNTs alone might function in drug release. The effect of
      the Ti surface with TNTs or TNTs-micelles on osteoblast-like MG-63 cells was
      determined by analyzing cell morphology, cytoskeletal arrangement, early
      adhesion, proliferation, alkaline phosphatase activity, and intracellular and
      extracellular osteocalcin content. The results indicate that the Ti surface with
      SV-loaded TNTs-micelles not only has better able to promote early adhesion,
      spreading and early differentiation of osteoblasts than the Ti surface with TNTs
      alone but it is able to promote calcification of osteoblasts. Therefore, a Ti
      surface with TNTs or TNTs-micelles is expected to promote contact osteogenesis of
      the Ti implant, thus contributing to early osseointegration of the implant,
      whereas the osteogenic effect of the Ti surface with TNTs-micelles is expected to
      be stronger. This local delivery system can bridge the gap between basic research
      and applied science for a wide range of titanium-based orthopedic implants in
      diverse bone-loss diseases, including osteoporosis.

PMID- 24738329
TI  - Treatment of rat with traumatic brain injury and MR tracing in vivo via combined
      transplantation of bone marrow stromal cells labeled with superparamagnetic iron
      oxide and Schwann cells.
AB  - Transplantation of bone marrow stromal cells (BMSCs) or Schwann cells (SCs) can
      facilitate axonal regeneration in nerve injuries. The aim of this study was to
      assess the effect of BMSCs and SCs transplantation on a rat with traumatic brain
      injury (TBI) and cellular migration in brain, and investigate whether combined
      BMSCs and SCs transplantations have more advantages than BMSCs transplantation
      alone. BMSCs were cultured in vitro and then labeled with SPIO. The labeled and
      unlabeled cells were assayed by MTT inspection to compare the effect of SPIO on
      growth activity of rat's BMSCs. Sciatic nerve was taken of the rat and striped
      off epineurium to obtain SCs by carrying out cell culture using mixed enzyme
      digestion. The SCs were identified by immunofluorescence labeling for S-100
      protein and cellular activities were analyzed by MTT growth curves. Improved
      Feeney method was adopted to make a rat TBI model. In total, 50 male Sprague
      Dawley (SD) rats weighing 200-250 g were randomly divided into 5 groups: Groups A
      E (n = 10 for each group). Injections of nutrient and stereotactic
      transplantation of BMSCs labeled with SPIO and stereotactic transplantation of
      SCs and BMSCs labeled with SPIO were administered in these groups 48 hours after
      TBI modeling. Neurological severity scores (NSS) were implemented at the 3 day, 1
      week, 2 week and 4 week, respectively, after transplantation and 7.0T MRI
      scanning was done to observe migration situation of transplanted cells. After
      completion of MRI inspection at 4 weeks post transplantation, all rats were
      sacrificed and their brain tissue sections taken and assayed by HE staining and
      prussian blue staining. Numerous BMSCs were successfully labeled with SPIO. The
      labeling efficiency was more than 90%. There was no obvious difference between
      cellular proliferation of BMSCs labeled and unlabeled with SPIO at different time
      points. SCs were cultured in vitro and SCs S-100 detected as positive. MRI
      results show that T2WI was expressed in low signal area and migrated towards
      injury side after BMSCs labeled with SPIO were transplanted into brain. The
      combined transplantation had a quicker migration speed than single
      transplantation. NSS result shows that the combined transplantation group had a
      low score than single transplantation group after 2 weeks. In conclusion, BMSCs
      labeled with SPIO can be transplanted into brain and can be used in 7.0T MRI
      tracing in vivo. Compared to single transplantation, the combined transplantation
      of BMSCs and SCs has a quicker cellular migration and a better prognosis.

PMID- 24738330
TI  - Magnetic resonance imaging-visible and pH-sensitive polymeric micelles for tumor
      targeted drug delivery.
AB  - Folate-functionalized copolymers of poly(ethylene glycol) and 2
      (diisopropylamino) ethylamine grafted poly(L-aspartic acid) are synthesized. The
      copolymers can self-assemble into nanoscaled micelles encapsulated with
      hydrophobic model drug Fluorescein Diacetate (FDA) and MRI diagnostic agents
      superparamagnetic iron oxide nanoparticles (SPIONs) in aqueous solution of a
      neutral pH resembling physiological environment, whereas disassemble in acidic
      endosomal/lysosomal compartments of tumor cells to achieve rapid drug release. In
      vitro drug release study showed that FDA release from the pH-sensitive micelles
      was much faster at pH 5.0 than at pH 7.4. Clustering of SPIONs inside the
      hydrophobic core of the micelles resulted in a high spin-spin (T2,) relaxivity
      for a super MRI sensitivity. Cell culture studies showed that the FDA-SPION
      loaded micelles were effectively internalized by human hepatic Bel-7402 cancer
      cells following a folate receptor-mediated targeting mechanism, and then FDA was
      rapidly release from micelles inside lysosomal compartments. Micelles
      encapsulating paclitaxel (PTX) studies showed it can induce more effective cell
      toxicity. This study demonstrated the great potential of the pH-sensitive
      micelles as an effective multifunctional nanomedician platform for cancer therapy
      due to their active tumor targeting, pH-triggered drug release and ultrasensitive
      MRI responsiveness.

PMID- 24738331
TI  - Enhanced 4T1 breast carcinoma anticancer activity by co-delivery of doxorubicin
      and curcumin with core-shell drug-carrier based on heparin modified poly(L
      lactide) grafted polyethylenimine cationic nanoparticles.
AB  - Use of single chemotherapy agents has shown some limitations in anti-tumor
      treatment, such as development of drug resistance, severe adverse reactions and
      limited regime for therapeutic use. Combination of two or more therapeutic drugs
      is a feasible strategy to overcome these limitations. This paper reports study of
      co-delivery by core-shell nanoparticles (NPs) with hydrophobic PLLA core loaded
      with curcumin (Cur) and hydrophilic heparin shell adsorbing Doxorubicin (DOX).
      Characterizations of Cur-PEA NPs, Cur-PEA/heparin NPs and DOX adsorbing into Cur
      PEA/heparin NPs (DOX-Cur NPs) were also investigated by transmission electron
      microscope (TEM) and Malvern Zetasizer. Studies on cellular uptake of DOX-Cur NPs
      demonstrated that both drugs were effectively taken up by 4T1 tumor cells.
      Furthermore, DOX-Cur NPs suppressed 4T1 tumor cells growth more efficiently than
      either DOX or Cur alone at the same concentrations, as measured by flow cytometry
      (FCM). We found out that intravenous injection of DOX-Cur NPs efficiently
      inhibited growth of subcutaneous 4T1 breast carcinoma in vivo (p < 0.01) and
      prolonged survival of the treated 4T1 breast carcinoma mice. Moreover, the
      pathological damage to the cardiac tissue in mice treated with DOX-Cur NPs was
      significantly less severe than that of mice treated with free DOX. This study
      suggested that DOX-Cur NPs may have promising applications in breast carcinoma
      therapy.

PMID- 24738332
TI  - Synthesis, characterization and biological activities of curcumin nanospheres.
AB  - Curcumin is one of the most versatile compounds obtained from Curcuma longa. The
      major obstacle in the therapeutic use of curcumin is its aqueous solubility. To
      enhance its aqueous solubility and biological activities, we prepared curcumin
      nanospheres (CNSs) by wet milling-solvent evaporation technique without any
      surfactants. In this study, we have focused on the synthesis, characterization
      and biological effects of CNSs. DLS and SEM analyses showed 50-80 nm spherical
      shaped CNSs with a zeta potential of -31.65 mV. FTIR revealed that there were no
      structural changes to CNSs. Antibacterial and antifungal studies proved that CNSs
      were much more effective than curcumin against Escherichia coil, Staphylococcus
      aureus and Candida albicans. Antioxidant activity of CNSs showed promising result
      for therapeutic applications. The in vitro anti-inflammatory studies proved that
      CNSs possessed enhanced anti-inflammatory effect against protein denaturation.
      Cytotoxicity and uptake of CNSs showed more toxicity on cancer cells (T47D, MG63,
      A375) sparing normal HDF and IEC cell lines. Skin permeation studies showed CNSs
      retained at different layers of pig skin. These results give clear evidence for
      their use against microbial and fungal skin infections as well as cancer
      treatment.

PMID- 24738333
TI  - Antitumor efficacy of DMSA modified Fe3O4 magnetic nanoparticles combined with
      arsenic trioxide and adriamycin in Raji cells.
AB  - The objective of the present study was to investigate the anticancer efficacy of
      dimercaptosuccinic acid modified iron oxide (DMSA-Fe3O4) magnetic nanoparticles
      (MNPs) combined with arsenic trioxide (As2O3) and doxorubicin (ADM) in non
      Hodgkin's lymphoma (NHL) cell line (Raji cells). The growth inhibition rate of
      Raji cells was determined by MTT assay. Characteristics of DMSA-Fe3O4 MNPs and
      distribution of nanoparticles taken up by Raji cells were observed under a
      transmission electron microscopy (TEM). Further, apoptosis of cells and
      intracellular concentration of ADM were detected by flow cytometry (FCM). DAPI
      staining was used to view apoptotic cellular morphology. Subsequently,
      transcription and protein expression levels of bcl-2, NFKB, survivin, bax, p53
      and caspase-3 were determined by reverse transciptase polymerase chain reaction
      (RT-PCR) and Western blotting analysis, respectively. The results of MTT assay
      indicated that the inhibition of Raji cells by the combined form of ADM and As2O3
      was significantly higher than either ADM or As2O3 alone. However, ADM-As2O3 MNPs
      proved superior over all other groups. TEM observation revealed that the majority
      of MNPs were quasi-spherical with an average diameter of about 18 nm and the MNPs
      taken up by cells were located in the endosome vesicles of cytoplasm. The
      apoptotic rate and accumulation of intracellular ADM in ADM-As2O3 MNPs group were
      significantly higher than those in control, ADM, As2O3 and ADM+As2O3, groups. In
      addition, DAPI staining of Raji cells from ADM-As,O3 MNPs group clearly exhibited
      more morphological changes (severe structural alterations) than other groups.
      Moreover, transcription and protein expression of bcl-2, NFKB, survivin, bax, p53
      and caspase-3 of Raji cells were regulated at the most remarkable extent in ADM
      As2O3, MNPs group as compared with other groups. These findings suggest that the
      antitumor efficacy of the combination of novel ADM-As2O3, MNPs on Raji cells
      would be a promising strategy for lymphoma therapy.

PMID- 24738334
TI  - Multifunctional superparamagnetic fe3O4@SiO2 core/shell nanoparticles: design and
      application for cell imaging.
AB  - Highly biocompatible sub-50-nm monodisperse superparamagnetic Fe3O4@SiO2
      core/shell nanoparticles with luminescent silica shells were synthesized by a w/o
      microemulsion technique. And then these nanoparticles were coated with the
      covalently bonded biocompatible polymer poly(ethylene glycol) (PEG) and modified
      with the biological cancer targeting ligand folic acid (FA). After characterized
      by means of powder X-ray diffraction (XRD), transmission electron microscopy
      (TEM), dynamic light scattering (DLS), Fourier transformed infrared spectroscopy
      (FT-IR), Thermogravimetric analysis (TGA), vibrating sample magnetometer (VSM),
      UV-vis, fluorescence spectroscopy and confocal laser scanning microscopy (CLSM),
      we confirmed that Fe3O4@SiO2 (FITC)-PEG-FA nanocomposites (SMNPs-FA) could be
      efficiently taken up by HeLa cancer cells and KB cells which are of over
      expression of folate receptors. The multifunctional nanomaterials exhibited
      superparamagnetic, monodisperse, highly biocompatible, intensively fluorescent
      and capable of recognizing and binding cells that overexpress folate receptors,
      which would be useful for targeting cell imaging and provide an excellent
      platform for further development of an efficient cancer therapy.

PMID- 24738335
TI  - Genetic immunotherapy for hepatocellular carcinoma by endothelial progenitor
      cells armed with cytosine deaminase.
AB  - Endothelial progenitor cells (EPCs) serve as cellular vehicles for targeting
      cancer cells and are a powerful tool for delivery of therapeutic genes. Cytosine
      deaminase (CD), a kind of frequent suicide gene which can kill carcinoma cells by
      converting a non-poisonous pro-drug 5-flucytosine (5-FC) into a poisonous
      cytotoxic 5-fluorouracil (5-FU). We combined super-paramagnetic iron oxide (SPIO)
      nanoparticles labeled EPCs with CD gene to treat grafted liver carcinomas and
      tracked them with 7.0 T Magnetic resonance imaging (MRI). Results showed that the
      therapeutic EPCs loaded with CD plus 5-Fc provided stronger carcinoma growth
      suppression compared with treatment using CD alone. The CD/5-Fc significantly
      inhibited the growth of endothelial cells and induced carcinoma cells apoptosis.
      These results indicate that EPCs transfected with anti-carcinoma genes can be
      used in carcinoma therapy as a novel therapeutic modality.

PMID- 24738336
TI  - Selective cytotoxicity effect of cerium oxide nanoparticles under UV irradiation.
AB  - During photodynamic therapy (PDT) of cancers, there are numerous side effects,
      accompanied by damage to normal cells/tissues caused by the abnormal elevation of
      reactive oxygen species (ROS). In this paper, we aim to provide an effective
      method to reduce the relevant side effects of PDT by using cerium oxide
      nanoparticles. The well-dispersed poly(vinyl pyrrolidone) stabilized cerium oxide
      nanoparticles were successfully synthesized by using a one-pot method at 60
      degrees C in slightly alkaline environment. The morphological and structural
      characterizations clearly illustrate the excellent lattice structures of cerium
      oxide, nanoparticles. The MTT assay indicates that these cerium oxide
      nanoparticles show no intrinsic cytotoxicity even at a concentration up to 300
      micro g/mL. More importantly, the results demonstrate that these nanoparticles
      can selectively protect human normal cells but not the cancer cells from ROS
      damage after exposure to UV-radiation, suggesting their potential applications
      for PDT treatment. The rationale behind the selective protection effect can be
      attributed to the hindrance of the Ce (III)/Ce (IV) redox reaction cycle on the
      surface of cerium oxide nanoparticles due to the abnormal intracellular pH in
      cancer cells. Furthermore, these cerium oxide nanoparticles can be used as
      effective drug carriers for enhancing drug delivery efficiency to target cancer
      cells like hepatoma HepG2 cells. This raises the possibility of applying cerium
      oxide nanoparticles for multifunctional therapeutic applications, i.e.,
      combination of efficient PDT and chemotherapy.

PMID- 24738337
TI  - Collagen functionalized bioactive nanofiber matrices for osteogenic
      differentiation of mesenchymal stem cells: bone tissue engineering.
AB  - Scaffold architecture, surface topography, biochemical and mechanical cues have
      been shown to significantly improve cellular events and in vivo tissue
      regeneration. Specifically electrospun nanofiber matrices have gained tremendous
      interest due to their intrinsic structural resemblance to native tissue
      extracellular matrix (ECM). The present study reports on the electrospun
      nanofiber matrices of polycaprolactone (PCL)-chitosan (CS) blends and effect of
      type I collagen surface functionalization in regulating rat bone marrow derived
      stromal cells (rBMSCs) differentiation into osteogenic lineage. Collagen was
      covalently attached to blend nanofibers via carbodiimide (EDC) coupling. Bead
      free smooth nanofibers (diameter-700-850 nm) obtained at the optimized conditions
      of polymer concentration and electrospinning parameters were used for the study.
      EDC collagen coupling resulted in 0.120+/-0.016 micro g of collagen
      immobilization onto a 1 cm2 area of the PCL/CS nanofibers, which was 2.6-folds
      higher than the amount of collagen that can be retained by physical adsorption.
      Significantly improved rBMSCs adhesion, spreading, proliferation and osteogenic
      differentiation was observed on the collagen functionalized COL-PCULCS nanofiber
      matrices as compared to control groups. Osteogenic phenotypic markers such as
      alkaline phosphatase (ALP) activity and mineralization were found to be
      significantly higher on COL-PCL/CS nanofiber matrices as compared to controls.
      Elevated gene expression profiles of osteogenic markers such as osteocalcin
      (0CN), osteopontin (OPN) and ALP further corroborate the osteoinductive nature of
      the collagen functionalized PCL/CS nanofiber matrices. These fiber matrices and
      modification techniques could be extended to other scaffold systems for tissue
      engineering applications.

PMID- 24738338
TI  - Reversal of tumor growth by gene modification of mesenchymal stem cells using
      spermine-pullulan/DNA nanoparticles.
AB  - Mesenchymal stem cells (MSCs) are a promising tool for delivering of therapeutic
      agents in cancer treatment. In the present study, our findings suggested that
      both i.v. and intratumoral injection of MSCs could favor tumor growth under
      physiologic conditions. However, the anti-tumor effects of MSC-IL-12 were
      achieved using our strategy. Unlike the previously reported method, the genetic
      engineering of MSCs was conducted by non-viral transfection using the new vector,
      spermine-pullulan. The transfection, cytotoxicity, and the cellular
      internalization of this vector were evaluated. Then, the therapeutical gene, IL
      12, was delivered to the MSCs using this vector. The in vitro secretions of IL-12
      by MSC-IL-12 confirmed the success of using spermine-pullulan/DNA nanoparticles
      for the gene transfection. We used the MSC-IL-12 for the in vivo treatment of
      both B16F10 metastasis tumor and the established subcutaneous B16BL6 tumor. For
      the B16F10 metastasis tumor, treatment with MSC-IL-12 significantly reduced lung
      metastases. For the established subcutaneous B16BL6 tumor, intratumoral injected
      MSC-IL-12 cells considerably retarded tumor growth. Prolonged survival was
      observed when MSC-IL-12 cells were injected through the tail vein or
      intratumorally, indicating that the MSCs engineered with the therapeutic gene
      could reverse the tumor-promoting effects of MSCs using the nonviral transduction
      method. However, the intravenous injected MSC-IL-12 did not prevent the tumor
      growth of the established subcutaneous B16BL6 tumor. Thus, we examined the the in
      vivo distribution of MSCs in different organs and it was found that MSCs were
      mainly distributed in the lungs, which may explain the inability of intravenously
      injected MSC-IL-12 to inhibit the growth of the established subcutaneous tumor.

PMID- 24738339
TI  - Evaluation of mechanical properties and therapeutic effect of injectable self
      assembling hydrogels for spinal cord injury.
AB  - Self-assembling peptides are promising biomaterials for spinal cord repair as
      they can easily be injected into the lesion site and can provide physical support
      to regrowing nervous tissue. However, to improve upon the design of synthetic
      scaffolds for spinal cord injury, characteristics of the scaffold/host
      relationship need to be further investigated. In the current study we aimed to
      evaluate both the mechanical properties and the therapeutic effect of two self
      assembling peptides B24 and biotin-LDLK12 in spinal cord injury. Atomic force
      microscopy and rheology were used to characterise various concentrations of the
      two peptides in terms of the propensity to form nanostructures and the
      viscoelastic properties. Concurrently, these peptide solutions were injected into
      the contused spinal cord of rats to evaluate both diffusibility within the
      tissue, and scaffold formation in vivo. After selection of the best concentration
      for delivery in vivo, the two self-assembling peptides were tested in the
      contused spinal cord of rats for their influence on hematoma and cyst formation,
      biocompatibility and permissiveness for axonal growth. The results suggest that
      rheology can provide a useful indication to predict the hydrogel formation and
      diffusibility of the self-assembling peptides in vivo. Moreover at three days
      post-injury both self-assembling peptides had a good hemostatic effect and at 28
      days they improved axon regrowth. In summary, the injectable self-assembling
      hydrogels could attenuate hematoma and provide a therapeutic effect in a spinal
      cord injury model.

PMID- 24738340
TI  - Preparation and in vitro evaluation of novel poly(anhydride-ester)-based
      amphiphilic copolymer curcumin-loaded micelles.
AB  - Novel poly(anhydride-ester)-b-poly(ethylene glycol) copolymers (PAE-b-PEGs) were
      synthesized by esterization of methyl poly(ethylene glycol) and poly(anhydride
      ester), which were obtained by the melt polycondensation of alpha,omega-acetic
      anhydride-terminated poly(L-lactic acid), and characterized by 1H-NMR and gel
      permeation chromatography. The two poly(anhydride-ester)-b-poly(ethylene glycols)
      (denoted as PAE-b-PEG2k and PAE-b-PEG5k) thus obtained can self-assemble in water
      to form micelles with hydrodynamic diameters of 92.5 and 97.5 nm above their
      critical micelle concentrations of 3.78 and 2.36 microg/mL, respectively. The
      curcumin-loaded PAE-b-PEG2k and PAE-b-PEG5k micelles were prepared by the solid
      dispersion method, and they could encapsulate approximately 7% (w/w) curcumin.
      The diameters of the micelles were stable for 5 days. Curcumin is released faster
      from the micelles at pH 5.0 than at pH 7.4. Curcumin is released from the
      micelles at a fast rate during the initial 12 h, followed by a zero-order release
      during the subsequent 200 h, both at pH 5.0 and 7.4. The IC50 values of the
      curcumin-loaded PAE-b-PEG2k and PAE-b-PEG5k micelles against HeLa cells are 12.41
      and 15.31 microg/mL, respectively, which is lower than that of free curcumin
      (25.90 microg/mL). The PAE-b-PEG2k micelles are taken up faster than the PAE-b
      PEG5k micelles by HeLa cells. Curcumin-loaded micelles can induce G2/M phase cell
      cycle arrest and apoptosis of HeLa cells.

PMID- 24738341
TI  - Gamma-Fe2O3 nanoparticles increase therapeutic efficacy of combination with
      paclitaxel and anti-ABCG2 monoclonal antibody on multiple myeloma cancer stem
      cells in mouse model.
AB  - Cancer stem cells (CSCs) are thought to be responsible for the relapse of
      multiple myeloma (MM). The objective of this study was to target therapy of MM
      cancer stem cells using gamma-Fe2O3@DMSA magnetic nanoparticle combination with
      paclitaxel and anti-ABCG2 monoclonal antibody, and to evaluate the combined
      therapeutic efficacy. CSCs were isolated from human MM cell line RPMI 8226 based
      on negative expression of CD138 and CD34. In vivo and in vitro studies
      demonstrated that the isolated CD138-CD34- cells displayed certain stem cell
      characteristics, including significant increase in expression of ABCG2
      transporter, proliferation, mobility, drug resistance, clonogenic potential in
      soft agar media and tumorigenecity in mice. Treatment with nanoparticles,
      paclitaxel and anti-ABCG2 antibody remarkably inhibited the growth of CD138-CD34-
      cells in vitro and their derived tumors in xenografts. The inhibition was also
      correlated with elevated expression of caspase-9, caspase-8 and caspase-3, and
      down-regulation of NF-KB. Our data indicate that the nanoparticle combination
      with paclitaxel and anti-ABCG2 monoclonal antibody offers an effective approach
      to treatment of MM CSCs through an apoptotic pathway.

PMID- 24738343
TI  - Inclusion of the helper lipid dioleoyl-phosphatidylethanolamine in solid lipid
      nanoparticles inhibits their transfection efficiency.
AB  - Solid lipid nanoparticles (SLNs) are a promising system for the delivery of
      lipophilic and hydrophilic drugs. They consist of a solid lipid core that is
      stabilized by a layer of surfactants. By the incorporation of cationic lipids in
      the formulation, positively charged SLNs can be generated, that are suitable
      carriers for nucleic acids (DNA, siRNA). Considering the beneficial effect of
      helper lipids on the transfection efficiency with cationic liposomes, the effect
      of the helper lipid 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE) on
      transfection with cationic lipid-containing solid lipid nanoparticles was
      investigated in PC3 prostate cancer cells. The inclusion of DOPE in SLN
      formulations, instead of promoted, strongly inhibited SLN transfection
      efficiency, by frustrating the accommodation of DNA by the particles, as was
      revealed by biochemical analysis. SLNs devoid of DOPE maintained a homogenous
      size distribution of approximately 150 nm following lipoplex assembly and
      cellular delivery, and showed transfection efficiency comparable to that of
      Lipofectamine 2000' (LF2k). Moreover, the SLNs maintain their high transfection
      efficiency after lyophilization and long-term storage (1-2 years), an important
      asset for biomedical applications. There is even the possibility to lyophilize
      the SLN carrier together with its DNA cargo, which represents an interesting
      pharmaceutical advantage of the SLN formulations over LF2k. These results reflect
      marked differences between the physicochemical properties of cationic liposomes
      and SLNs, the latter requiring more critical lipid-depending properties for
      effective 'packaging' of DNA but displaying a higher storage stability than
      cationic lipid based carriers like LF2k.

PMID- 24738342
TI  - Enhancing biodistribution of therapeutic enzymes in vivo by modulating surface
      coating and concentration of ICAM-1-targeted nanocarriers.
AB  - Coupling therapeutic proteins to targeted nanocarriers can enhance their
      biodistribution. This is the case for enzyme replacement therapies where
      intravenously injected enzymes must avoid prolonged blood exposure while reaching
      body organs. We have shown enhanced tissue targeting of various lysosomal enzymes
      by coupling to nanocarriers targeted to intercellular adhesion molecule-1 (ICAM
      1). Here, we varied design parameters to modify tissue enzyme levels without
      affecting specific targeting and relative biodistribution. We coupled a
      galactosidase (aGal; affected in Fabry disease) to model polymer nanocarriers and
      varied enzyme load (50 vs. 500 molecules/particle), anti-ICAM surface density (80
      vs. 180 molecules/particle), and nanocarrier concentration (1.6 x 1013 vs. 2.4 x
      1013 carriers/kg) to render three formulations (45, 449, 555 microg alphaGal/kg).
      Naked alpha Gal preferentially distributed in blood vs. organs, while
      nanocarriers shifted biodistribution from blood to tissues. Accumulation in
      brain, kidneys, heart, liver, lungs, and spleen did not vary among nanocarrier
      formulations, with enhanced specific tissue accumulation compared to naked aGal.
      The highest specificity was associated with lowest antibody density and
      nanocarrier concentration, but highest enzyme load; possibly because of
      synergistic enzyme affinity toward cell-surface markers. Variation of these
      parameters significantly increased absolute enzyme accumulation. This strategy
      may help optimize delivery of lysosomal enzyme replacement and, likely, other
      protein delivery approaches.

PMID- 24738344
TI  - Artificial biomimicking matrix modifications of nanofibrous scaffolds by hE
      cadherin-Fc fusion protein to promote human mesenchymal stem cells adhesion and
      proliferation.
AB  - Extracellular matrix (ECM) plays a fundamental role in regulating cell
      attachment, proliferation, migration and differentiation. Both synthetic and
      biologically derived materials have been explored as an ECM in regenerative
      medicine and tissue engineering. To biomimick the extracellular matrix, we
      combined the advantages of the biological properties of nanofibrous scaffolds and
      the fusion protein to apply for the culture of human mesenchymal stem cells in
      vitro. In this study, we fabricated well random-oriented/aligned nanofibrous
      scaffolds with PCL, modified with hE-cadherin-Fc fusion protein and studied the
      synergistic effect of the scaffolds. The random-oriented/aligned architecture was
      observed in the nanofibrous scaffolds by SEM. XPS and WCA measurements evidenced
      that hE-cadherin-Fc was successfully modified on the PCL nanofibrous scaffolds
      and hydrophilicity of the scaffolds was well improved after fusion protein
      coating. The hE-cadherin-Fc modified markedly promoted the adhesion and
      proliferation of hMSCs and guided hMSCs to a spindlier morphology compared with
      unmodified nanofibrous scaffolds. Furthermore, hMSCs on the hE-cadherin-Fc-coated
      nanofibrous scaffolds also had differentiation potential. These results suggested
      that the combination of PCL nanofibrous scaffolds and hE-cadherin-Fc fusion
      protein may be a promising artificial ECM for the behavior of hMSCs in vitro.

PMID- 24738345
TI  - A non-genetic approach to labelling acute myeloid leukemia and bone marrow cells
      with quantum dots.
AB  - The difficulty in manipulation of leukemia cells has long hindered the dissection
      of leukemia pathogenesis. We have introduced a non-genetic approach of marking
      blood cells, using quantum dots. We compared quantum dots complexed with
      different vehicles, including a peptide Tat, cationic polymer Turbofect and
      liposome. Quantum dots-Tat showed the highest efficiency of marking hematopoietic
      cells among the three vehicles. Quantum dots-Tat could also label a panel of
      leukemia cell lines at varied efficiencies. More uniform intracellular
      distributions of quantum dots in mouse bone marrow and leukemia cells were
      obtained with quantum dots-Tat, compared with the granule-like formation obtained
      with quantum dots-liposome. Our results suggest that quantum dots have provided a
      photostable and non-genetic approach that labels normal and malignant
      hematopoietic cells, in a cell type-, vehicle-, and quantum dot concentration
      dependent manner. We expect for potential applications of quantum dots as an easy
      and fast marking tool assisting investigations of various types of blood cells in
      the future.

PMID- 24738346
TI  - Gd@C82(OH)22 nanoparticles constrain macrophages migration into tumor tissue to
      prevent metastasis.
AB  - Macrophages can be recruited to tumor tissues and play a supportive role in the
      invasion microenvironment. Since nanoparticles can be easily endocytosed by this
      kind of cell, the advances in nanotechnology offer a new sight to target
      macrophages in tumor tissues for diminishing harmful phenotypes. In the xenograft
      mouse model, we found that metallofullerol Gd@C82(OH)22 can not only reduced the
      macrophage density in the tumor tissue, but also decreased the expression of
      matrix metalloproteinase-9 produced by this kind of cell. To verify the
      phenomenon, a macrophage cell line, RAW264.7 was employed in the experiment, in
      vivo. Gd@C82(OH)22 nanoparticles can be engulfed by macrophages and the quantity
      was measured by inductively coupled plasma mass spectrometry. Fluorescent
      staining result showed that the particle induced the cells to adopt an elongated
      spindle morphology. The morphology alteration implied that the cells undergo
      mesenchymal migration, which is assisted by matrix metalloproteinase-9 to break
      down the extracellular matrix. But the reverse transcription PCR and western
      blots results indicated that the expression of matrix metalloproteinase-9 was
      reduced after the treatment of Gd@C82(OH)22. Thus, transwell migration assay
      indicated that macrophages were constrained to migrate through the collagen
      matrix.

PMID- 24738347
TI  - A label-free gold nanocluster fluorescent probe for protease activity monitoring.
AB  - Water soluble BSA-stabilized gold nanoclusters (Au NCs) were synthesized with a
      simple one-pot procedure. The as-prepared Au NCs were able to emit intensive red
      fluorescence under the excitation of ultraviolet light, and the fluorescence
      could be quenched by enzymatic hydrolysis. In this contribution, BSA-stabilized
      Au NCs as novel fluorescent probes were successfully utilized for the detection
      and real-time monitoring of proteolytic activity of trypsin and chymotrypsin.
      High performance liquid chromatography-inductively coupled plasma mass
      spectrometry, X-ray photoelectron spectroscopy, and X-ray absorption fine
      structure were performed to investigate the quenching mechanism, and the results
      indicated that BSA scaffold degradation caused by enzymatic proteolysis led to
      the decrease in fluorescence intensity. Furthermore, this method would be
      potentially extended to the detection of other enzymes with Au NCs stabilized by
      different biomolecules.

PMID- 24738348
TI  - Fluorescence resonance energy transfer based immunosensing of human IgG by using
      quantum dot/GIgG-gold nanoparticles/IgG conjugation.
AB  - A novel immunosensor of human immune globulin (IgG) was fabricated based on the
      fluorescence transfer between luminescent semiconductor quantum dots (QDs) and
      gold nanoparticles (AuNPs). AuNPs and CdSe/ZnS QDs were respectively labeled with
      immune reaction pair:IgG and goat anti-human immunoglobulin (GIgG), by optimizing
      the conditions including pH value and protein amount. In the assembled QD-GIgG
      IgG-AuNP fluorescence resonance energy transfer (FRET) immunocomplex system, the
      presence of AuNP-IgG directly reduced the fluorescence intensity of the GIgG
      conjugated QDs. As a result, the concentration of AuNP-IgG had a linear
      relationship with the fluorescence decrease in a range of 0-1.57 microg/mL.
      Furthermore, the mechanism of the QDs' fluorescence decay has also been discussed
      and attributed to the light-induced photobleaching. This novel sensing method
      achieves quantitative detection of trace proteins, suggesting the potential of
      biomolecule-AuNPs conjugation based analytical methods in further application.

PMID- 24738349
TI  - Immunoglobulin molecules detection with nanopore sensors fabricated from glass
      tubes.
AB  - Nanopores are increasingly utilized as tools for single molecule detection in
      biotechnology. Here, we report an improved fabrication process to make solid
      state nanopores from glass tubes with the help of paraffin. Based on the physical
      footprint of the phase change of the paraffin, nanocavity is formed in the broken
      terminal after thermally compressing and pulling the glass capillary. Nanopores
      with the minimum diameter of 50 nm are fabricated. Different immunoglobulin
      molecules including IgG, IgA, IgM mixed in a 10 mM KCl solution are used to test
      the sensing capabilities of the glass-nanopore sensor. Various modulated ionic
      current modes were observed while the the three type immunoglobulin molecules
      translocate the nanopore because the molecules had different size and structure.
      Based on the difference in the duration time and amplitude of the transient
      electrical pulse signals, we are able to discriminate the three immunoglobulin
      molecules.

PMID- 24738350
TI  - Electrochemical sensing of H2O2 by the modified electrode with pd nanoparticles
      on multi-walled carbon nanotubes-g-poly(lactic acid).
AB  - A simple method has adapted to prepare MWCNT grafted Poly(lactic acid) (MWCNT-g
      PLA) by intercalative polymerization of poly(lactic acid) in the presence of
      multi-wall carbon nanotubes (MWCNT) functionalized with hydroxyl groups. The
      functionalized MWCNT has obtained from the treatment of methylene diphenyl
      diisocyanate (MDI) with MWCNT, and then the reaction with 1,4-butanediol (BD) to
      create functional hydroxyl groups. MWCNT-g-PLA-Pd and MWCNT-g-PLA-Pt have
      prepared from the MWCNT-g-PLA and metal precursors. The synthesized materials
      have characterized by 1H-NMR, Fourier transform infrared spectroscopy (FT-IR),
      Raman spectroscopy, X-ray photoelectron spectroscopy (XPS), transmission electron
      microscopy (TEM). The MWCNT-g-PLA-Pd is possibilities for employing to
      electrochemical detection of hydrogen peroxide. Electrocatalytic activities are
      verified from cyclic voltammetry (CV) and amperometric response in 0.1 M
      phosphate buffer solution (PBS). The biosensor provided good stability and
      selectivity towards interferences such as UA, AA, and glucose.

PMID- 24738351
TI  - Embedded carbon nanotubes nanoparticles in plasma membrane induce cellular
      calcium outflow imbalancing.
AB  - In this report, embedded single-wall carbon nanotubes (SWCNTs) nanoparticles in
      plasma membrane inducing cellular calcium outflow imbalancing are disclosed.
      Compared ssDNA-SWCNTs with polystyrene (PS) nanoparticles, we analyzed the
      cytotoxicity of these nanoparticles and the effect of these nanoparticles on
      intracellular Ca2+ ion levels by depletion of Ca2+ from the endoplasmic reticulum
      (ER) evoked by Thapsigargin (Tg) in SKN-SH cells. The results had shown that
      ssDNA-SWCNTs and PS nanoparticles have no cytotoxicity on SKN-SH cells. However,
      contrary to PS nanoparticles, cellular Ca2+ ion outflow imbalancing was
      investigated in SKN-SH cells after pretreated with ssDNA-SWCNTs induced by Tg,
      which could be proposed mainly due to the interaction of embedded ssDNA-SWCNTs
      with cellular membrane.

PMID- 24738352
TI  - LX loaded nanoliposomes synthesis, characterization and cellular uptake studies
      in H2O2 stressed SH-SY5Y cells.
AB  - In this study, we report the cellular uptake studies of novel LX loaded
      nanoliposomes in H2O2 stress SH-SY5Y Cells synthesized by thin film evaporation
      method. We have isolated the smallest size nanoliposomes after 90 min
      ultrasonification, keeping Polydisperse Index as 0.259. The morphology, size,
      zepta potential and drug efficiency of prepared nanoliposomes are characterized
      by using Transmission Electron Microscope (TEM), particle size analyzer and High
      Pressure Liquid Chromatography (HPLC). The particle size analyzer have confirmed
      the particle size of nanoluposomes measured in range of 100-250 nm, whereas the
      shape of these nanoliposomes is almost spherical. The zeta potential of small
      size nanoliposomes was measured as -49.62 and encapsulation efficiency of the LX
      loaded nanoliposomes was 87%. The oxidative stress response in SH-SY5Y Cells for
      various doses of drug with and without nanoliposomes has affectively improved the
      cell-stress response up to 20% after 24 h of incubation at 37 degrees C. The
      results indicated that LX loaded nanoliposomes were taken by the cells
      effectively which ultimately improved the cell-stress response. Thus, this study
      confirmed that synthesized nanoliposomes are not only effective drug carriers but
      could be potentially used for delivery of genes, antibodies, and proteins in
      future.

PMID- 24738353
TI  - Aspect ratio dependent fluorescence quenching of eosin Y by gold nanorods.
AB  - Gold nanorods of different aspect ratios had been synthesized using seed mediated
      growth method. The formed gold nanorods had been characterized by the absorption
      and transmission electron microscopy (TEM) measurements. The obtained gold
      nanorods were used to study the quenched effect on fluorescence of Eosin Y.
      Experimental results revealed that Eosin Y molecules adsorbed on the metallic
      surfaces, suffering strong quenching of their fluorescence and the quenching
      efficiency was different for different aspect ratio. Using dielectric coated gold
      nanorods model, the probable mechanism of aspect ratio dependent quenching
      efficiency was obtained by numerical calculation based on fluorescence resonance
      energy transfer and quasi-static theory. The calculation results showed that the
      non-monotonic changing of fluorescence quenching was attributed to competing
      effects of aspect ratio and the dielectric constant of coated shell on surface
      plasmon resonance.

PMID- 24738354
TI  - Fast detection of alpha-fetoprotein-L3 using lens culinaris agglutinin
      immobilized gold nanoparticles.
AB  - Colloidal gold is extensively used for molecular sensing because that the surface
      plasmon resonance (SPR) bands are affected by changes in the dielectric
      properties in the close vicinity of these structures due to the binding of
      ligands to the corresponding receptor molecules immobilized onto the
      nanostructures through chemi- or physisorption. We describe a simple method for
      the detection of Alpha-Fetoprotein-L3 which is a new generation of tumor marker
      for hepatocellular carcinoma (HCC) based on the aggregation of Lens culinaris
      agglutinin (LCA) Immobilized Gold Nanoparticles. The LCA conjugated GNPs obtained
      were 15-20 nm in diameter. The visible color change of the gold nanoparticles
      from purple to blue on interaction with 100 ng/mL of AFP-L3 is the principle
      applied here for the sensing of AFP-L3 level. UV/Vis spectroscopy also allows
      assay monitoring by quantifying the red shift of the plasmon resonance
      wavelength. With this method, the protein AFP-L3 can be rapidly detected as
      demanded for clinical diagnosis.

PMID- 24738355
TI  - Dual pH and temperature stimuli-responsive magnetic nanohydrogels for thermo
      chemotherapy.
AB  - Dual stimuli pH and temperature-responsive nanohydrogels based on poly(N
      isopropylacrylamide)-chitosan have been synthesized. Fe3O4 magnetic nanoparticles
      (NPs) (-12 nm) have been incorporated into hydrogels to achieve temperature
      optimized magnetic nanohydrogel (MNHG) for magnetic hyperthermia with lower
      critical solution temperature, LCST > 42 degrees C. The composite was further
      investigated for its potential application in drug delivery and in vitro cancer
      cell cytotoxicity. Water-bath assisted drug release studies were carried out
      using anti-cancer drug doxorubicin (DOX) in acetate buffer medium (pH - 4.6) to
      mimic tumor cell environment which is slightly acidic in nature. The pH and
      temperature responsiveness of the system was demonstrated by DOX release under
      different conditions. The released amount of DOX was found to be nearly 4
      microg/mg above hyperthermia temperature (-42 degrees C) as opposed to only 1.9
      microg/mg of MNHG at physiological temperature (37 degrees C) under acidic
      environment (pH - 4.6). Further, AC magnetic field (AMF) induced heating of NPs
      entrapped inside hydrogels showed appreciable reduction of cell population in
      human breast (MCF-7) and cervical carcinoma (HeLa) cell lines for given duration
      of field exposures. Quantitatively, death percentages of HeLa cells were nearly
      35 and 45% while for MCF-7, these were 20 and 70% when exposed to AMF for 10 and
      30 min, respectively. Further the cell killing efficacy of MNHG loaded with DOX
      was assessed under AMF using HeLa cell lines. The AMF induced heat triggered DOX
      release from the MNHG which enhances the cell death up to 85% due to combined
      effect of thermo-chemotherapeutics. The present system with both pH and
      temperature responsivity serves as a promising candidate for a combination
      therapy.

PMID- 24738356
TI  - Plasmon-assisted photocurrent generation from silver nanoparticle monolayers
      combined with porphyrins via their different chain-length alkylcarboxylates.
AB  - Three-typed porphyrin derivatives with a different chain-length alkylcarboxylic
      acid as their peripheral anchor group have been prepared. Anodic photocurrents
      were observed in a simple system where the porphyrin derivatives were directly
      anchored on an indium tin oxide (ITO) electrode. Cathodic photocurrents and their
      plasmon-assisted enhancement appeared from an Ag nanoparticle (Ag NP) composite
      monolayer combined with the porphyrin derivatives on the ITO electrode. In the
      photocurrent generation mechanism, Ag NPs played both the roles as photon- and
      energy-transfer to the porphyrin derivatives. The plasmon-assisted enhancement
      was affected by the chain-lengths of the peripheral anchor groups.

PMID- 24738357
TI  - Preparation of cocrystal nanofibres of cobalt octaethylporphyrin and
      tetracyanoquinodimethane with good photoresponse.
AB  - Cocrystal nanofibres of cobalt octaethylporphyrin and tetracyanoquinodimethane
      were prepared by a facile solution method and fully characterized by SEM, AFM,
      XRD, Raman, EDX, and UV-vis-NIR. The as-prepared cocrystal nanofibres had smooth
      surfaces and uniform dimension. When incorporated into prototype devices, they
      exhibited good photoresponse at ambient conditions. Additionally, the
      phototransistor characteristics with a maximum I(on)/I(off) ratio of -460 was
      demonstrated. The facile synthesis and good photoresponse may boost the potential
      applications of cocrystal-based nanostructures in future miniaturized devices.

PMID- 24738358
TI  - Al3+ ions dependent structural and magnetic properties of Co-Ni nano-alloys.
AB  - Ferrite samples with a chemical formula Co0.5Ni0.5Al(x)Fe(2-x)O4 (where x = 0.0,
      0.25, 0.5, 0.75 and 1.0) were synthesized by sol-gel auto-combustion method. The
      synthesized samples were annealed at 600 degrees C for 4 h. An analysis of X-ray
      diffraction (XRD) patterns reveals the formation of single phase cubic spinel
      structure. The lattice parameter decreased linearly with the increasing Al
      content x. Nano size of the powders were confirmed by the transmission electron
      micrographs (TEM). Particle size, bulk density decreased whereas specific surface
      area and porosity of the samples increased with the Al substitution. Cation
      distribution of constituent ions shows linear dependence of Al substitution.
      Based on the cation distribution obtained from XRD data, structural parameters
      such as lattice parameters, ionic radii of available sites and the oxygen
      parameter 'u' is calculated. Saturation magnetization (M(s)), magneton number
      (n(B)) and coercivity (H(c)) decreased with the Al substitution. Possible
      explanation for the observed structural and magnetic behavior with various Al
      content are discussed.

PMID- 24738359
TI  - Controllable synthesis of Cu2O/Cu composites with stable photocatalytic
      properties.
AB  - Here we reported a facile approach to synthesize Cu2O/Cu composite particles by
      one-step sono-chemical process. The content of Cu in the Cu2O/Cu composites can
      be easily controlled by adjusting the synthesis time. Phase, morphology and
      optical properties of the products were carried out by X-ray diffraction (XRD),
      field-emission scanning electron microscopy (FSEM), transmission electron
      microscope (TEM), ultraviolet-visible (UV-vis) spectroscopy and nitrogen
      adsorption apparatus. Using photocatalytic degradation of Methyl orange (MeO) dye
      under visible-light illumination, we have investigated the influence of Cu on the
      photocatalytic activity of Cu2O, to find out its potential application in waste
      water treatment. Especially, the stability of the photocatalyst was confirmed
      using reclaimed Cu2O/Cu in ten successive runs. Results demonstrated clearly that
      Cu2O/Cu were stable and resistant to photocorrosion during the photocatalytic
      oxidation of organic compounds, indicating that these Cu2O/Cu composites are
      promising candidates for pollutant processing.

PMID- 24738360
TI  - Effect of cation trapping on thermal stability of magnetite nanoparticles.
AB  - We investigate the effect of sodium trapping on thermal stability of magnetite
      (Fe3O4) nanoparticles. The pure magnetite nanoparticles incubated in sodium
      hydroxide solutions and subsequently washed with water to remove the excess
      sodium. The amount of sodium in magnetite is measured using atomic absorption
      spectroscopy. The size distribution obtained from Small angle X-ray scattering
      measurements show that particles are fairly monodisperse. The FTIR spectra of
      nanoparticles show transmission bands at 441 and 611 cm(-1) are due to the
      symmetric stretching vibrations (v) of Fe-O in octahedral and tetrahedral sites
      respectively. With 500 ppm of sodium ions (Na+) in magnetite, the cubic ferrite
      structure of maghemite (gamma-Fe2O3) to hexagonal hematite (alpha-Fe2O3) phase
      transition is enhanced by -150 degrees C in air. The Rietveld analysis of sodium
      doped magnetite nanoparticles show that above 99% of metastable gamma-Fe2O3 is
      converted to a thermodynamically stable alpha-Fe2O3 after air annealing at 700
      degrees C. A decrease in enthalpy observed in doped magnetite unambiguously
      confirms that the activation energy for maghemite to hematite transition is
      increased due to the presence of trapped sodium ions. These results suggest that
      the trapped cations in ferrite nanoparticles can stabilize them by increasing the
      activation energy.

PMID- 24738361
TI  - Quantitative biokinetics and systemic translocation of various gold
      nanostructures are highly dependent on their size and shape.
AB  - Gold nanostructures with promising applications in biomedical field have
      attracted great attention. However, some fundamental questions other than the
      development of novel applications should be elucidated before they can actually
      serve as biomedicines in the clinic. Bio-safety is one of the most important
      issues. Since numerous modifications (e.g., surface coating and composites) have
      been designed on gold nanoparticles (GNPs) to extend their application, there
      would be hundreds of GNPs synthesized in the lab although the prototypes of GNPs
      (i.e., cluster, shell, rod, sphere, cage, and star) are rather limited. Thus, in
      the present work we aim to conduct our experiments only on the most basic types
      of GNPs--including gold nanocluster (GNC), gold nanorod (GNR) and gold nanosphere
      (GNS), to investigate their biodistribution and toxicities in vivo, in the hope
      of revealing some basic rules which could be further extended to other
      complicated situations. Bovine serum albumin (BSA) was coated at the surface to
      increase their plasma stability and of the same BSA coating would help to compare
      the fate and behaviors of various GNPs in vivo. After intravenous administration
      of different GNPs with an equal content of gold element at 0.5 mg/kg in mice,
      samples were harvested at a series of time points. Biodistribution was compared
      among different GNPs and the process of accumulation-retention-clearance of each
      kind of GNP was also observed through quantification analysis by inductively
      coupled plasma-mass spectrometry (ICP-MS). The results showed, with the same BSA
      coating at the surface and similar negative charge, size rather than shape was
      dominating the in vivo fate of GNPs. Even between GNC and hydrolyzed GNC with
      their size at 7.1 and 3.2 nm, huge difference in the kidney accumulation was
      observed. Totally, GNR and GNS in relative large size preferred to accumulate in
      liver and spleen whereas GNC in relative small size tended to accumulate in liver
      and kidney. GNPs resided in liver were hardly cleared out of body till 28 d
      whereas their accumulation in kidney was almost entirely eliminated with
      prolonged time, although not as rapid as reported in previous work. In vivo
      toxicities evaluated by pathology observation and blood biochemical analysis also
      revealed slight liver and kidney damage, basically associated with the
      biodistribution pattern of GNPs.

PMID- 24738362
TI  - Enhancement and regulation of fluorescence emission from NaYF4:Yb3+, Er3+
      nanocrystals by codoping Mn2+ ions.
AB  - NaYF4:Yb3+, Er3+, Mn2+ nanocrystals with cubic crystal phase were obtained by a
      facile solvothermal method through doping a proper amount of Mn2+ ions to the
      nanocrystals. The results of XRD and TEM showed that the as-prepared samples were
      well crystallized and their average size was about 25 nm. Under excitations at
      978.5 nm and at 532 nm, obvious enhancement and regulation of upconversion and
      downconversion fluorescence were obtained. Upconversion emission spectra indicate
      that these effects were independent of doped concentrations of Er3+ and Yb3+,
      excitation power, and the excitation wavelength in the current study. It is
      concluded that the enhancement of fluorescence emissions is mainly due to the
      change of local symmetry around Er3+ ions, while the regulation of red-to-green
      ratios was caused by efficient energy transfer between Er3+ and Mn2+ ions. This
      kind of upconversion material has a great potential in bioimaging and drug
      delivery since the excitation and emission falls into the region of "optical
      window" of biological tissues.

PMID- 24738363
TI  - In-situ and ex-situ chitosan-silver nanoparticle composite: comparison of
      storage/release and catalytic properties.
AB  - In this work storage of silver nanoparticles (Ag NPs) in chitosan gel and its
      subsequent release for catalytic reduction processes is investigated. The
      generation of small sized metal nanoparticles which acts as catalyst is
      prerequisite to progress of a catalytic reaction. We show that Ag NPs extracted
      from chitosan gel are less than 5 nm so very effective in catalysis. Chitosan-Ag
      nanocomposite gels were prepared from two different approaches. The first
      approach involves in-situ incorporation of Ag nanoparticles into the reaction
      mixture while preparing the chitosan hydrogel and termed as chitosan-Ag-in-situ
      (CH-Ag-I) nanocomposite gel. And, in second approach already prepared chitosan
      hydrogel was placed in Ag NPs solutions, resulting in adsorption of Ag NPs and
      thus forming chitosan-Ag-ex-situ (CH-Ag-E) nanocomposite gel. The prepared gels
      were characterized by UV-Visible spectroscopy, Fourier transformed infra-red
      spectroscopy (FTIR), Thermogravimetric analysis (TGA) and Scanning electron
      microscopy (SEM). Swelling studies showed that the CH-Ag-E exhibits efficient
      water absorption property compared to that of CH-Ag-I. In addition to efficient
      swelling properties the CH-Ag-E can also act as store house of Ag NPs that can be
      used to catalyze the reduction of 4-Nitrophenol (4-NP) to 4-Aminophenol (4-AP) as
      Ag NPs of this composite can be easily extracted just by treating with sodium
      borohydride which is not possible in case of CH-Ag-I. The rate of the reaction
      increases upto 10 fold when CH-Ag-E nanocomposite gel is used as catalyst in
      comparison to CH-Ag-I. The reduction reaction catalyzed by such Ag NPs follow
      zero order kinetics and dependent on the size of the Ag NPs loaded in the gel (CH
      Ag-E) as well as on the amount of the gel used. We found that smaller is the size
      of the loaded Ag NPs in CH-Ag-E, more effective it is in catalyzing the reduction
      reaction. The CH-Ag-E gel also showed reusability with efficient catalysis.

PMID- 24738364
TI  - Design and fabrication of carbon quantum dots/TiO2 photonic crystal complex with
      enhanced photocatalytic activity.
AB  - TiO2 photonic crystal photocatalyst with inverse opal structure were first
      prepared from self-assembled polystyrene spheres template, and then carbon
      quantum dots (CQDs) was coupled with TiO2 inverse opal through a facile
      electrodeposition method. The obtained CQDs/TiO2 complex photocatalysts exhibit
      enhanced photocatalytic activity compared to pure TiO2 inverse opal, especially
      under the irradiation of visible light. Our results provide a promising
      methodology for designing high performance photocatalysts based on photonic
      crystal and CQDs, which is benefit for catalytic and new energy applications.

PMID- 24738365
TI  - Enhanced conversion efficiency in dye-sensitized solar cells based on bilayered
      nano-composite photoanode film consisting of TiO2 nanoparticles and nanofibers.
AB  - Novel TiO2 nanoparticles/nanofibers (NPs/NFs) bilayered nano-composite photoanode
      film for dye-sensitized solar cells (DSSCs) was fabricated through the
      combination of spin-coating and electrospinning. The NPs and NFs layers have
      complementary roles. The underlaid spin-coated NPs layer provides the photoanode
      film with higher specific surface area for dye adsorption and improved adhesion
      to conductive glass substrate. The overlaid electrospun NFs layer endows the
      photoanode film with better dye-loading and light-harvesting capabilities due to
      its porous meshwork structure. And the NFs layer also offers larger pore volume,
      which can facilitate the electrolyte diffusion and the activity regeneration of
      dye sensitizers. As a result, the electron transport is accelerated while the
      charge recombination is suppressed. Ascribing to the synergic effect of the NPs
      and NFs layers, the TiO2 NPs/NFs-based DSSCs achieve a conversion efficiency of
      4.46%, which is nearly 14% higher than that of the pure TiO2 NPs-based ones.

PMID- 24738366
TI  - Fabrication of In2S3 nanoparticle decorated TiO2 nanotube arrays by successive
      ionic layer adsorption and reaction technique and their photocatalytic
      application.
AB  - In2S3 nanoparticle (NP) decorated self-organized TiO2 nanotube array (In2S3/TiO2
      NT) hybrids were fabricated via simple successive ionic layer adsorption and
      reaction (SILAR) technique. The In2S3 NPs in a size of about 15 nm were found to
      deposit on the top surface of the highly oriented TiO2 NT while without clogging
      the tube entrances. The loading amount of In2S3 NPs on the TiO2 NT was controlled
      by the cycle number of SILAR deposition. Compared with the bare TiO2 NT, the
      In2S3/TiO2 NT hybrids showed stronger absorption in the visible light region and
      significantly enhanced photocurrent density. The photocatalytic activity of the
      In2S3/TiO2 NT photocatalyst far exceeds that of bare TiO2 NT in the degradation
      of typical herbicide 2,4-dichlorophenoxyacetic acid (2,4-D) under simulated solar
      light. After 160-min irradiation, almost 100% 2,4-D removal is obtained on the 7
      In2S3/TiO2 NT prepared through seven SILAR deposition cycles, much higher than
      26% on the bare TiO2 NT. After 10 successive cycles of photocatalytic process
      with total 1,600 min of irradiation, In2S3/TiO2 NT maintained as high 2,4-D
      removal efficiency as 95.1% with good stability and easy recovery, which
      justifies the potential of the photocatalytic system in application for the
      photocatalytic removal of organic pollutants such as herbicides or pesticides
      from water.

PMID- 24738367
TI  - Electrical transport model of Silicene as a channel of field effect transistor.
AB  - The analytical electrical transport model of the Silicene, a single layer of sp3
      bonded silicon atoms in the honeycomb lattice structure as a channel in the field
      effect transistor configuration is presented in this paper. Although the carrier
      concentration of the Silicene shows similar behavior to Graphene, there are some
      differences in the conductance behavior. Presented model shows increment in the
      total carrier and the conductance with the gate voltage as expected for
      conventional semiconductors which affected by the temperature only in the
      neutrality point. The minimum conductance is increased by the temperature whereas
      it remains stable in the degenerate regime. Presented analytical model is in good
      agreement with the numerical conductance calculation based on the implementation
      of the non-equilibrium Green's function method coupled to the density functional
      theory.

PMID- 24738368
TI  - Highly visible-light-responsive photocatalytic AgCl/BiOCl hetero-nanostructures
      synthesized by a chemical coprecipitation method.
AB  - AgCl/BiOCl heteronanostructures were synthesized by a room-temperature chemical
      coprecipitation method. The as-obtained products were characterized by energy
      dispersive X-ray spectroscopy (EDS), transmission electron microscopy (TEM), X
      ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS) and UV-Vis diffuse
      spectra, which show the structures, morphologies, and optical properties. The
      results revealed that the absorption edge of AgCl/BiOCl shifted towards visible
      light regions. Meanwhile, the AgCl/BiOCl heteronanostructures showed better
      photocatalytic properties than the pure BiOCl to degrade rhodamine B and the 5%
      AgCl/BiOCl showed the best photocatalytic ability, which completely decomposed
      the target molecules in 17 minites with the visible-light illumination. The
      formation of heteronanostructures might improve the separation of photogenerated
      electrons and holes derived from the coupling effect of BiOCl and AgCl
      heteroarchitectures, which was regarded as the main reason for the high
      photocatalytic activity.

PMID- 24738369
TI  - Efficient infrared luminescence of Er2S3/ZnS core/shell quantum dots and IR QDs
      lED.
AB  - We have synthesized Er2S3/ZnS core/shell QDs by employing ErSt3, ZnSt2, and
      sulfur as precursors via a hot solution phase chemistry using a nucleation-doping
      strategy. X-ray diffraction (XRD), transmission electron microscope (TEM) and
      photoluminescence (PL) spectra were used to characterize the structure,
      morphology and luminescence properties of Er2S3/ZnS core/shell QDs. Moreover, the
      influence of overcoating temperatures on the infrared luminescence properties of
      QDs was investigated. PL spectra show that the emission intensity from the 4I13/2
      --> 4I15/2 transition of Er3+ strongly increases with increasing overcoating
      temperatures, which was interpreted by the enhancing diffusion of Er3+ ions. IR
      LEDs were fabricated combining commercial red GaAs LEDs with Er2S3/ZnS QDs, and
      luminescence properties of the IR-LED have been investigated.

PMID- 24738370
TI  - Spectroscopic properties of Yb3+ doped CaNb2O6 phosphor.
AB  - The spectroscopic measurements of orthorhombic CaNb2O6 phosphor doped with Yb3+
      ions have been performed. Low temperature spectra indicate that Yb3+ ions may
      occupy three types of nonequivalent sites inside the CaNb2O6 lattice: a main Yb3+
      site dominating the near-infrared emission, and two other minor sites of similar
      behaviors to each other. An attempt to determine the Stark sublevels energies of
      the 2F7/2 and 2F5/2 manifolds of three Yb3+ nonequivalent ions was carried out.
      The fluorescence lifetimes associated to the emission lines of Yb3+ ions located
      at the main site and minor sites are also quite different. Furthermore, there
      exists energy transfer from the main site to the minor sites.

PMID- 24738371
TI  - Synthesis and characterization of carbon nanofibers by catalytic chemical vapor
      deposition using non-ferromagnetic metal complexes.
AB  - Carbon nanofibers (CNFs) have wide applications in energy storage devices,
      electrically conducting composites, selective adsorbents, and catalyst supports.
      Catalytic chemical vapor deposition was carried out in this work to synthesize
      CNFs at mild temperatures of 700 and 800 degrees C. Non-ferromagnetic metal
      complexes of La, Nb, and Ti, spread on porous NaX-type zeolite support, were
      tested as new catalyst. CNFs ranging from 30 to 200 nm in diameter were obtained.
      Images of transmission electron microscopy showed encapsulated transition-metal
      nanoparticles by CNFs. X-ray diffraction patterns revealed the crystalline
      structures of La (FCC), Nb (BCC), and Ti (HCP) formed over zeolite. Magnetic
      hysteresis loops showed superconductivity from the CNF-encapsulated Nb at 2 K.
      Raman spectra showed that all the samples possessed graphitic and amorphous
      carbon structures. Based on the SEM images and Raman spectra, the three metals
      all catalyzed the synthesis of CNFs.

PMID- 24738372
TI  - Fabrication and upconversion luminescence properties of YF3:Er3+ hollow
      nanofibers via monoaxial electrospinning combined with fluorination method.
AB  - YF3:Er3+ hollow nanofibers were successfully fabricated via fluorination of the
      relevant Y2O3:Er3+ hollow nanofibers which were obtained by calcining the
      electrospun PVP/[Y(NO3)3 + Er(NO3)3] composite nanofibers. The morphology and
      properties of the products were investigated in detail by X-ray diffraction
      (XRD), scanning electron microscope (SEM), transmission electron microscope
      (TEM), and fluorescence spectrometer. YF3:Er3+ hollow nanofibers were pure
      orthorhombic phase with space group Pnma and were hollow-centered structure with
      the mean diameter of 172 +/- 23 nm, and YF3:Er3+ hollow nanofibers were composed
      of nanoparticles with the diameter ranging from 30 nm to 50 nm. Upconversion
      emission spectrum analysis manifested that YF3:Er3+ hollow nanofibers emitted
      strong green and weak red upconversion emission centering at 524 nm, 543 nm and
      653 nm, respectively. The green emissions and the red emission were respectively
      originated from 2H11/2/4S3/2 --> 4I15/2 and 4F9/2 --> 4I15/2 energy levels
      transitions of the Er3+ ions. Moreover, the emitting colors of YF3:Er3+ hollow
      nanofibers were located in the green region in CIE chromaticity coordinates
      diagram. The luminescent intensity of YF3:Er3+ hollow nanofibers was increased
      remarkably with the increasing doping concentration of Er3+ ions. The possible
      formation mechanism of YF3:Er3+ upconversion luminescence hollow nanofibers was
      also discussed. This preparation technique could be applied to prepare other rare
      earth fluoride upconversion luminescence hollow nanofibers.

PMID- 24738373
TI  - Application of solution-processed V2O5 in inverted polymer solar cells based on
      fluorine-doped tin oxide substrate.
AB  - We used a hydrothermal method to synthesis the solution-processed V2O5 as anode
      buffer layer, which applied on inverted polymer solar cells based on FTO
      substrate. The structure of the device is glass/FTO/TiO2/P3HT:PCBM/V2O5/Ag. We
      discussed the dependence of device performance on the concentrations of V2O5
      solution. It is found that when the concentration of V2O5 is 300 microg/ml, the
      power conversion efficiency (PCE of 2.38%) is the highest, which is much higher
      than that of the device without anode buffer layer (PCE of only 0.87%). Moreover,
      it can significantly reduce the energy consumption and make it more cost
      effective.

PMID- 24738374
TI  - Metal-ceramic/ceramic nanostructured layered composites for solid oxide fuel
      cells by spark plasma sintering.
AB  - In this work, bi-layered Fe-Ni-Co-YSZ/YSZ nanostructured composites for solid
      oxide fuel cells were obtained using the spark plasma sintering (SPS) technique.
      The microstructures of the anode and electrolyte were controlled by optimization
      of SPS consolidation parameters. The resulting bilayers have a full dense YSZ
      electrolyte and porous Fe-Ni-Co/YSZ anode as well as crack-free and well-bonded
      anode/electrolyte interface. On the other hand, SPS under non-optimized
      processing parameters cannot yield the desired results. The high resistance to
      thermal stresses of the fabricated half-cells was achieved with Fe-Ni-Co/YSZ
      anode. The developed anode showed higher thermal compatibility with YSZ
      electrolyte than usual Ni/YSZ cermet. Thus, with the successful combination of
      SPS parameters and anode material, we have obtained bi-layers for SOFCs with
      required microstructure and thermal compatibility.

PMID- 24738375
TI  - Hydrothermal synthesis of tetragonal BaTiO3 nanotube arrays with high dielectric
      performance.
AB  - Tetragonal Barium titanate (BaTiO3) nanotube arrays have been prepared using the
      template-assisted hydrothermal method combined with an annealing process. The in
      situ chemical conversion of TiO2 nanotube array templates ensured that BaTiO3
      maintained the morphology of the nanotube architectures. Moreover, X-ray
      diffraction and Raman spectrum characterization were used to confirm that the
      BaTiO3 nanotube arrays had a tetragonal phase after the use of a simple annealing
      technique. Typical hysteresis loops showed their ferroelectricity, with the
      remanent polarization and coercive fields being 2.57 microC/cm2 and 2.52 kV/cm,
      respectively. The relative dielectric constant of the tetragonal BaTiO3 nanotube
      arrays reached up to 1000 and the dielectric loss was as low as 0.02 at 1 kHz at
      room temperature.

PMID- 24738376
TI  - Fabrication and performance of contamination free individual single-walled carbon
      nanotube optical devices.
AB  - Contamination free individual single-walled carbon nanotube (SWCNT) optical
      devices are fabricated using a hybrid method in the purpose of increase
      sensitivity as well as further understanding the sensing mechanism. The devices
      were tested in vacuum to avoid contamination. Three typical devices are discussed
      comparatively. Under infrared lamp illumination, photovoltaic and photoconductive
      properties are revealed in device A and B respectively, while device C shows no
      detectable signal. The photoresponse of device B reaches 108% at 78 K, much
      larger than that of horizontally aligned or network carbon nanotube devices,
      indicating priority of the individual nanotube device structure. Interestingly,
      the temperature characteristics of device A and B are just the opposite. The
      individual SWCNT devices hold promise in high performance and low cost optical
      sensors as well as nano-scale solar cells.

PMID- 24738377
TI  - General route to synthesize of metal (Ni, Co, Mn, Fe) oxide nanostructure and
      their optical and magnetic behaviour.
AB  - Here we report a generalised way to prepare transitional metal (Ni, Co, Mn, Fe)
      oxide nanostructures via solvothermal route followed by controlled heat
      treatment. The method has been successfully involved to produce structurally
      uniform and well crystalline phase of the different metal (Ni, Co, Mn) oxide
      faceted nanoparticles and porous nanorods (Fe2O3) with highly anisotropic
      surfaces. The product materials were characterized by the X-ray powder
      diffraction and electron microscope (SEM, TEM) to investigate the structural and
      morphological details. Optical absorption study was carried out by UV-VIS
      spectrophotometer and the results are analysed on the basis of their electronic
      transitions of 3d shell and band energies. The details magnetic investigation was
      carried out by the measurement of magnetization with varying magnetic field and
      temperature. The observed magnetic behaviour is explained on the basis of
      uncompensated spins lying on the surface which is extremely anisotropic in the
      present systems of the synthesized materials.

PMID- 24738378
TI  - Localized surface plasmon resonance and surface enhanced Raman scattering
      responses of Au@Ag core-shell nanorods with different thickness of Ag shell.
AB  - The properties of the localized surface plasmon resonance (LSPR) and the surface
      enhanced Raman scattering (SERS) of the core-shell bimetallic nanostructures,
      that is the monodisperse Au@Ag core-shell nanorods with different thickness of Ag
      shell, are theoretically and experimental researched. The UV-vis-NIR absorption
      spectra of the Au@Ag core-shell nanorods are measured and displayed their blue
      shifts of the longitudinal plasmon resonance peaks with increasing of Ag
      concentrations in the colloidal solution. And the absorption spectra of the Au@Ag
      core-shell nanorods are simulated by the Finite Element Method (FEM), which are
      in agreement with the experimental measurements and reveal their LSPR mechanism
      as the varying structures. In addition, Rhodamine 6G, as a Raman reporter
      molecule, is used to investigate SERS of gold nanorods and Au@Ag core-shell
      nanorods. It is found that Au@Ag core-shell nanorods have better SERS responses,
      comparing with those of Au nanorods, and their SERS intensities are increased
      with the increases of the Ag shell thickness, which demonstrate that the
      chemisorptive bond effect and the morphology of the nanoparticle play key roles
      to the SERS signals. It is significant to design the biosensor based on the
      properties of Au@Ag core-shell nanorods.

PMID- 24738379
TI  - Effects of synthesizing parameters on surface roughness and contact angles of ZnO
      nanowire films.
AB  - Effects of the synthesizing parameters on the surface roughness and the contact
      angles of ZnO nanowire films were studied in this paper. ZnO nanowire films were
      synthesized with the hydrothermal method on glass substrates, and the
      synthesizing parameters include the concentrations of the growth solution and the
      seed layer solution, the growth time span as well as the temperature. Atomic
      force microscopy and scanning electron microscopy were employed respectively to
      characterize the surface and the profile roughness of ZnO nanowire films. The
      measurement results by atomic force microscopy were in agreement with that by
      scanning electron microscopy, hence the former was used for the investigation of
      aforementioned effects. Relationships between the synthesizing parameters, the
      surface roughness and the contact angles of ZnO nanowire films were established,
      revealing that the synthesizing parameters affected significantly not only the
      surface roughness but also the contact angles of ZnO nanowire films. The results
      can be used for batch fabrication of ZnO nanowire-based structures and these
      structures-based sensors in a wide variety of applications.

PMID- 24738380
TI  - Agarose gel tailored calcium carbonate nanoparticles-synthesis and
      biocompatibility evaluation.
AB  - In this study, a novel approach to tailor the calcium carbonate nanoparticles was
      exploited based on agarose gel as polymer medium. The size of nanoparticles
      formed was governed by ionic diffusion and affected by weight percent of agarose
      and reaction temperature. The size, shape, purity, composition and allotropy of
      the synthesized nanoparticles were analyzed by different characterization
      techniques. Purity of nanoparticles as small as 37 nm demonstrates their
      suitability for broad range of industrial applications. The exposure of rat lung
      epithelial cells to these nanoparticles even at a higher concentration (50
      microg/ml) did not induce considerable oxidative stress or cell death
      authenticating their fidelity to potential applications in the field of
      biotechnology and medicine. Through the simple and economic method of synthesis
      adopted in this study, separation of nanoparticles from the gel was easy, and
      process parameters could be optimized to control the particle size.

PMID- 24738381
TI  - ZnO nanocrystals anchored graphene: in situ solvothermal synthesis and enhanced
      photocatalytic performance.
AB  - ZnO nanocrystals anchored graphene composite (ZnO/G) was synthesized by a facile
      in situ solvothermal route. The nanocomposite was characterized by X-ray
      diffraction (XRD), scanning electron spectroscopy (SEM), transmission electron
      microscopy (TEM) and Raman spectra (RS). The results indicated that the ZnO
      particles with an average diameter of ca. 12.6 nm were well-dispersed on the
      surface of the graphene nanosheets. The optical properties were investigated by
      fluorescence (PL) and UV diffuse reflectance (UV-VIS). It showed that the
      nanocomposite displayed a fluorescence quenching property. Furthermore, the
      nanocomposite showed a remarkably enhanced photocatalytic activity to degrade
      organic pollutants (MB, MO, Rh-B) under visible light irradiation, with a
      percentage degradation of MB reaching as high as 99.8% in 60 min.

PMID- 24738382
TI  - Characterisation and thermal properties of titanium dioxide nanoparticles
      containing biodegradable polylactide composites synthesized by sol-gel method.
AB  - This study reports the synthesis, characterisation and thermal properties of
      polylactide (PLA)/titanium dioxide nanoparticles (TiO2 NPs) composites using the
      sol-gel method. The percentage weight of TiO2 NP sol was varied from 3, 8, 11 and
      14. The synthesised composites were characterised using scanning electron
      microscopy (SEM), Fourier transform infrared (FTIR) spectroscopy, X-ray
      diffraction, energy dispersive X-ray spectroscopy (EDS), thermogravimetric
      analysis and dynamic mechanical analysis. Encapsulation of the TiO2 into the PLA
      matrix was attainable based on the SEM images and the FTIR and EDS results. The
      thermal stability of the composites was shifted to lower temperatures due to
      photodegradation induced by the metal oxide on the PLA chain. Both PLA and TiO2
      NPs have potential in drug delivery because of their biocompatibility and
      biodegradability.

PMID- 24738383
TI  - Green and economical synthesis of carbon-coated MoO2 nanocrystallines with highly
      reversible lithium storage capacity.
AB  - Carbon-coated MoO2 nanocrystallines with uniform particle size and carbon-coating
      morphology have been fabricated by a green and economical hydrothermal route and
      carbonization process. Glucose here acts as a multifunctional agent, not only as
      the reducing species to prepare MoO2, but also as the carbonaceous precursor and
      coating agent to form the carbon-coated and nanoscale MoO2 crystallines. The
      electrochemical tests demonstrate that the as-synthesized carbon-coated MoO2
      nanocrystallines exhibit high capacity and excellent capacity retention as an
      anode material for lithium-ion batteries. The specific discharge capacity is as
      high as 790 mA h g(-1) in the first cycle and 730 mA h g(-1) over 50 cycles. The
      significant enhancement in the electrochemical Li storage performance is
      attributed to the synergistic effect of the nanocrystallines structure with small
      particle size and uniform carbon-coating shell, which reduces the diffusion
      distance for Li-ion and electron, provides high electric conductivity and
      relieves the volume effect during the cycling.

PMID- 24738384
TI  - Role of solution pH on the microstructural properties of spin coated cobalt oxide
      thin films.
AB  - Cobalt Oxide (Co3o4) thin films have been successfully coated onto glass
      substrates at various solution pH by sol-gel spin coating technique. The film
      thickness was estimated using weight gain method and it revealed that the film
      thickness increased with solution pH values. The prepared film structural,
      morphological, optical and electrical properties were studied using X-ray
      diffraction (XRD), scanning electron microscope (SEM), UV-Vis-NIR
      spectrophotometer and Vander Pau method, respectively. The structure of the films
      were found to be face centered cubic with preferential orientation along (311)
      plane. X-ray line profile analysis was used to evaluate the micro structural
      parameters such as crystallite size, micro strain, dislocation density and
      stacking fault probability. The crystallite size values are increased with
      increase of solution pH values and maximum value of crystallite is estimated at
      40.8 nm at solution pH 8 +/- 0.1. Morphological results showed that the pH of the
      solution has a marked effect on morphology of the Co3O4 thin films. The optical
      studies revealed that the band gap can be tailored between 2.16 to 2.31 eV by
      altering pH. The thin film formed at a solution pH 7 is found to have a low
      resistivity and high mobility. The electrical resistivity (p), carrier
      concentration (n) and mobility (micro) values are 0.1 x 10(3) omega x cm, 8.9 cm2
      gammas(-1) and 6.6 x 10(14) cm(-3), respectively for Co3O4 thin film prepared at
      solution pH 7 +/- 0.1. EDAX studies showed that the cobalt content increased and
      the oxygen content decreased with increase of pH.

PMID- 24738385
TI  - Electrically conductive and mechanically elastic titanium nitride ceramic
      microsprings.
AB  - The structural and functional characterizations of titanium nitride (TiN)
      advanced ceramic microsprings (CMSs), with a coil diameter of several micrometers
      and synthesized by chemical vapor deposition (CVD) were investigated by
      microscopy techniques. The CMSs were sufficiently mechanically elastic for
      extension to more than 1.3 times their original size, and they spontaneously
      contracted to their original state on releasing the tension. To explore their
      application to a microdevice, a method of manufacturing TiN-CMS microcircuit
      elements was developed. The I-V plots of the elements indicated that the CMSs
      were as conductive as metals.

PMID- 24738386
TI  - Visual detection of Hg2+ based on Hg(2+)-xanthine complex preventing aggregation
      of gold nanoparticles.
AB  - Xanthine, which can specifically bind with mercury ion (Hg2+) to form xanthine
      Hg(2+)-xanthine complex, was used as Hg2+ binding molecule in this paper. In the
      absence of Hg2+, imide group of xanthine easily adsorbs onto the surface of gold
      nanoparticles (AuNPs) and induces aggregation of AuNPs, resulting in a blue
      color. In the presence of Hg2+, however, the selective binding of xanthine with
      Hg2+ prevents the AuNPs against xanthine induced aggregation, resulting in a
      visible color change from blue to red depend on the concentration of Hg2+.
      Therefore, taking advantage of this phenomenon, a simple, cost-effective and
      rapid method can be established for Hg2+ visual detection. This method allows the
      detection of Hg2+ in the range of 0.075-4.0 microM with a detection limit
      (3sigma/slope) of 15 nM, and exhibits a high selectivity toward Hg2+ over other
      metal ions. Particularly, as low as 0.5 microM Hg2+ can be easily detected by the
      naked eye without using any complicated or expensive instruments.

PMID- 24738387
TI  - Characterization and humidity sensing properties of the sensor based on Na2Ti3O7
      nanotubes.
AB  - Na2Ti3O7 nanotubes was synthesized by a hydrothermal method, and characterized by
      X-ray diffraction (XRD), scanning electron microscopy (SEM), and transmission
      electron microscopy (TEM). Then the material was coated on Al2O3 ceramic
      substrate to fabricate humidity sensors using Ag-Pd as interdigitated electrodes.
      The sensor shows high humidity sensitivity and quick response-recovery time. The
      impedance changes about five orders of magnitude within humidity range from 11%
      to 95% relative humidity (RH). At the frequency of 100 Hz, the response time is 2
      s and recovery time is 4 s, and the maximum hysteresis is less than 3% RH.
      Moreover, complex impedance property at different RH was investigated to study
      sensing mechanism. The results indicate the potential applications of Na2Ti3O7
      nanotubes for fabricating high-performance humidity sensors.

PMID- 24738388
TI  - Pr3+/Yb3+ co-doped beta-phase NaYF4 microprisms: controlled synthesis and
      upconversion luminescence.
AB  - Pr3+/Yb3+ co-doped hexagonal NaYF4(beta-NaYF4) microprisms were synthesized by
      the hydrothermal method, and ethylenediaminetetraacetic acid (EDTA) was
      introduced to control the size of the microcrystal samples. Bright upconverted
      fluorescence emission was observed when the samples were excited with an infrared
      (IR) laser at 976.4 nm. The emission was found to originate from the transitions
      of 3P0-3F2, 3P0-3H6 or 1G4-3H4, 3P1-3H6, 3P0-3H5, 3P1-3H5, and 3P0-3H4 of Pr3+
      ions. Possible mechanisms for upconversion fluorescence and concentration
      dependence as well as the crystal structure and its formation of NaYF4:Yb3+/Pr3+
      microprisms were explored and discussed based on the experimental observations.

PMID- 24738389
TI  - Near-infrared to visible upconversion in Tm3+ and Yb3+ codoped Lu2O3 nanocrystals
      synthesized by hydrothermal method.
AB  - Lutetium oxide nanocrystals codoped with Tm3+ and Yb3+ have been successfully
      synthesized via adjusting the pH values of the precursor solution in a
      hydrothermal method followed by a subsequent calcination process. The samples
      were systematically characterized by X-ray diffraction, field-emission scanning
      microscopy, Fourier transform infrared transmittance spectroscopy, and
      upconversion luminescent spectra. The experimental results show that the pH
      values of the precursor solution have great effects on the structural,
      morphological, and upconversion luminescent properties of Lu2O3:2%Yb3+, 0.2%Tm3+
      nanocrystals. The as-formed lutetium oxide precursors could transform to cubic
      Lu2O3 with the same morphology and a slight shrinkage in size after a calcination
      process. The upconversion emission intensity of Lu2O3:2%Yb3+, 0.2%Tm3+
      nanocrystals obtained from the precursor solution with pH = 9 is the strongest.
      The enhancement of the upconversion luminescence is suggested to be the
      consequence of reducing the number of OH- groups and the enlarged nanocrystals
      size. Strong blue and weak red emissions from the prepared nanocrystals were
      observed under 980 nm laser excitation, which were attributed to the 1G4 --> 3H6
      and 1G4 --> 3F4 transitions of Tm3+ ion, respectively.

PMID- 24738390
TI  - Local field effect on the photoluminescent spectra of Eu3+ ions in glass.
AB  - To investigate the effect of the dielectric medium on the spontaneous emission
      rate of an isolated emitter, two series of glass samples of various compositions
      lightly doped with the Eu3+ ion were prepared by melt-quenching method. According
      to the enhancement factors for emission rates due to the refractive index of the
      dielectric medium, we qualitatively analyzed the intensities of the electric
      dipole and magnetic dipole transitions by comparing the emission spectra of the
      samples with different compositions, viz. various refractive indices. This
      preliminary result indicates that the local-field effect on the spontaneous
      emission rates follows the virtual-cavity model, which is derived by assuming
      that single-ion emitters enter the medium without disturbing the medium, i.e., as
      interstitial ions or by replacing host ions of low polarizability.

PMID- 24738391
TI  - Highly stable gelatin layer-protected gold nanoparticles as surface-enhanced
      Raman scattering substrates.
AB  - Amine and carboxylic groups rich gelatin was used as reducing and stabilizing
      agent to form highly stable gold nanoparticles for surface-enhanced Raman
      scattering (SERS) applications. The size of the particle was determined to be 13
      nm by TEM with mono-dispersity. The size of the gold nanoparticles was little
      affected by the initial gelatin concentration. The gelatin-gold nanoparticles
      show strong SERS activity with Rhodamine 6G and Ruthenium bipyridine as reporter
      molecules. Both carboxylic acid groups and amine groups were identified by FT-IR
      to be present on the gelatin-gold nanoparticle surface, providing the possibility
      of further conjugation with other molecules. The gelatin-protected gold
      nanoparticles prepared by this simple, green, method displayed very good
      solubility and stability in many solvents, and good monodispersity, all desirable
      features as good SERS substrates.

PMID- 24738392
TI  - Utilization of carbon nanotubes for the removal of rhodamine B dye from aqueous
      solutions.
AB  - Carbon nanotubes (CNTs) are attracting increasing research interest as promising
      adsorbents for harmful cations, anions, and other organic and inorganic
      impurities present in natural sources of water. This study examined the
      feasibility of removing Rhodamine B dye from aqueous solutions using multi walled
      carbon nanotubes (MWCNTs) synthesized by chemical vapor deposition (CVD) method.
      The effects of dye concentration, pH and contact time on adsorption of direct dye
      by CNTs were also evaluated. The study used the Langmuir and Temkin isotherms to
      describe equilibrium adsorption. Additionally, pseudo second-order model was
      adopted to evaluate experimental data and thereby elucidate the kinetic
      adsorption process. The adsorption percentage of dye increased as contact time
      increased. Conversely, the adsorption percentage of dye decreased as dye
      concentration increased. The pseudo second-order model best represented
      adsorption kinetics. The capacity of CNTs to adsorb Rhodamine B was 65-90% at
      different pH values.

PMID- 24738393
TI  - The effect of coolants on the performance of magnetic micro-refrigerators.
AB  - Magnetic refrigeration is an alternative cooling technique with envisaged
      technological applications on micro- and opto-electronic devices. Here, we
      present a magnetic micro-refrigerator cooling device with embedded micro-channels
      and based on the magnetocaloric effect. We studied the influence of the coolant
      fluid in the refrigeration process by numerically simulating the heat transfer
      processes using the finite element method. This allowed us to calculate the
      cooling power of the device. Our results show that gallium is the most efficient
      coolant fluid and, when used with Gd5Si2Ge2, a maximum power of 11.2 W/mm3 at a
      working frequency of -5 kHz can be reached. However, for operation frequencies
      around 50 Hz, water is the most efficient fluid with a cooling power of 0.137
      W/mm3.

PMID- 24738394
TI  - Influence of polyelectrolyte multilayer coating on the degree and type of
      biofouling in freshwater environment.
AB  - Biofouling is one of the biggest problems of water-borne systems. Since not only
      marine but also freshwater-based structures are affected, the biofouling in this
      environment is studied. The focus of this study lies on the antifouling
      properties of novel coating materials like polyelectrolyte multilayers (PEM)
      compared with currently used silicon rubber (PDMS) based fouling release
      coatings. The following article contains the results of a systematical screening
      of the mechanical, surface charge and surface nano-heterogeneous properties of
      the investigated PEM and PDMS systems. The results show that negatively charged
      non crosslinked and crosslinked PEM coated PDMS can surpass current PDMS based
      fouling release coatings. The PEM films are not only able to reduce the
      biofouling, but are additionally able to control the type of settled bacteria
      (gram positive or negative). The negative terminated surfaces inhibit the
      settlement of gram positive bacteria, whereby the positive terminated surfaces
      inhibit the settlement of gram negative bacteria.

PMID- 24738395
TI  - Control of adhesion force between ceria particles and polishing pad in shallow
      trench isolation chemical mechanical planarization.
AB  - The adhesion force between ceria and polyurethane (PU) pad was controlled to
      remove the step height from cell region to peripheral region during Shallow
      Trench Isolation Chemical Mechanical Planarization (STI-CMP) for NAND flash.
      Picolinic acid was found to be adsorbed on ceria particles at pH 4.5 following a
      Langmuir isotherm with the maximum adsorbed amount of 0.36 mg/m2. The ceria
      suspension with full surface coverage of picolinic acid showed a threefold
      increase in the number of adhered ceria particles on the PU pad over non-coated
      ceria particles. It was shown that the coverage percent of picolinic acid on
      ceria corresponds well with the amount percent of adsorbed ceria on PU pad. The
      change in adsorbed particles was directly reflected in the CMP polishing process
      where significant improvements were achieved. Particularly, convex areas on the
      chip experienced higher friction force from the attached abrasives on the PU pad
      than concave areas. As a result, the convex areas have increased removal rate of
      step height compared to the ceria suspension without picolinic acid. The changing
      profiles of convex areas are reported during the step height reduction as a
      function of polishing time.

PMID- 24738396
TI  - The role of silver and gold nanoparticles in enhancing luminescence of europium
      complexes.
AB  - The influence of 12 nm spherical silver nanoparticles (AgNPs) and 20 nm spherical
      gold nanoparticles (AuNPs) on the luminescence of europium complex Eu(TTFA)3 were
      studied. When 350 nm is chosen as the incident light, the maximum enhancement
      factor of the complexes mixed with AgNPs is about 2.5 at the wavelength of 612
      nm. Besides the enhancement of the localized field, the overlap between the
      localized surface plasmon resonance spectra of nanoparticles and the absorption
      band of fluorescent molecules is another important factor for excitation field
      enhancement. By means of the quasi-static approximation theory, the distribution
      of the electric field around a single spherical metallic nanopaticle illuminated
      by plane wave was calculated. The simulation results show that the field
      enhancement effect is more obvious when the incident light is close to the
      resonance of the metallic nanoparticle, which could be demonstrated by our
      following experimental results. The distribution of the electric field under the
      same conditions was also simulated through the COMSOL software. The results are
      consistent with those of the quasi-static approximation theory.

PMID- 24738397
TI  - Multiplex PCR based on a universal biotinylated primer to generate templates for
      pyrosequencing.
AB  - Pyrosequencing is a powerful tool widely used in genetic analysis, however
      template preparation prior to pyrosequencing is still costly and time-consuming.
      To achieve an inexpensive and labor-saving template preparation for
      pyrosequencing, we have successfully developed a single-tube multiplex PCR
      including a pre-amplification and a universal amplification. In the process of
      pre-amplification, a low concentration of target-specific primers tagged with
      universal ends introduced universal priming regions into amplicons. In the
      process of universal amplification, a high concentration of universal primers was
      used for yielding amplicons with various SNPs of interest. As only a universal
      biotinylated primer and one step of single-stranded DNA preparation were required
      for typing multiple SNPs located on different sequences, pyrosequencing-based
      genotyping became time-saving, labor-saving, sample-saving, and cost-saving. By a
      simple optimization of multiplex PCR condition, only a 4-plex and a 3-plex PCR
      were required for typing 7 SNPs related to tamoxifen metabolism. Further study
      showed that pyrosequencing coupled with an improved multiplex PCR protocol
      allowed around 30% decrease of either typing cost or typing labor. Considering
      the biotinylated primer and the optimized condition of the multiplex PCR are
      independent of SNP locus, it is easy to use the same condition and the identical
      biotinylated primer for typing other SNPs. The preliminary typing results of the
      7 SNPs in 11 samples demonstrated that multiplex PCR-based pyrosequencing could
      be promising in personalized medicine at a low cost.

PMID- 24738398
TI  - Synthesis and characterization of CoFe2O4/polyaniline nanocomposites for
      electromagnetic interference applications.
AB  - The Cobalt ferrite (CoFe2O4) powders were synthesized by Co-precipitation method.
      The as prepared ferrite powders were incorporated into a polyaniline matrix at
      various volumetric ratios. The as prepared composites of ferrite and polyaniline
      powders were characterized using X-ray diffraction (XRD), transmission electron
      microscope (TEM). The particle size of CoFe2O4 is found to be 20 nm. The
      saturation magnetization (M(s)) of all the composites was found to be decreasing
      with decrease of ferrite content, while coercivity (H(c)) remained at the value
      corresponding to pure cobalt ferrite nanopowders. The complex permittivity
      (epsilon' and epsilon") and permeability (mu' and mu") of composite samples were
      measured in the range of 1 MHz to 1.1 GHz. The value of epsilon' and mu' found to
      be increased with ferrite volume concentration.

PMID- 24738399
TI  - Synthesis of gold and silver nanoparticles using leaf extract of Perilla
      frutescens--a biogenic approach.
AB  - The present investigation demonstrates a rapid biogenic approach for the
      synthesis of gold and silver nanoparticles using biologically active and
      medicinal important Perilla frutescens leaf extract as a reducing and stabilizing
      agent under ambient conditions. Gold and silver nanoparticles were first
      synthesized from Perilla frutescens leaf extract which was used as a vegetable
      and in traditional medicines for a long time in Korea, Japan, and China. The
      nanoparticles obtained were characterized by UV-vis spectroscopy, transmission
      electron microscopy, X-ray diffraction, and Fourier transform infrared
      spectroscopy. Surface plasmon resonance spectra of gold and silver nanoparticles
      were obtained at 540 and 430 nm and triangular and spherical shape respectively.
      TEM studies showed that the particle sizes of gold and silver nanoparticles
      ranges -50 nm and -40 nm respectively. X-ray diffraction studies confirm that the
      biosynthesized nanoparticles were crystalline gold and silver. Fourier transform
      infra-red spectroscopy revealed that biomolecules were involved in the synthesis
      and capping of the nanoparticles produced. XRD and EDX confirmed the formation of
      gold and silver nanoparticles. This is a simple, efficient and rapid method to
      synthesize gold and silver nanoparticles at room temperature without use of toxic
      chemicals. Obtained gold and silver nanoparticles can be used in various
      biomedical and biotechnological applications.

PMID- 24738400
TI  - Enhanced photocatalytic efficacy of hetropolyacid pillared TiO2 nanocomposites.
AB  - The removal of dye from industrial effluents is prime important, photo-catalysis
      is a finest method to combat dye from effluents. This study concerns about the
      investigation of photocatalytic activity of TiO2-HPAs (Hetropolyacids)
      nanocomposite namely TiO2-Phosphomolybdic nanocomposite [TiO2-HMA] and TiO2
      Phosphotungstic nanocomposite [TiO2-HWA] which were prepared by Sol-gel method
      and the same were characterized by using XRD, SEM-EDAX. The photocatalytic
      activity of prepared photo-catalysts were evaluated and compared by the
      degradation of Methylene Blue dye in water solution under UV irradiation. In that
      TiO2-HMA nanocomposite showed superior photocatalytic activity than TiO2-HWA.

PMID- 24738401
TI  - The effect of Ti anodized nano-foveolae structure on preosteoblast growth and
      osteogenic gene expression.
AB  - The TiO2 nanotubes by anodization have been extensively studied for medical
      implant and orthopedic applications because of enhancing bone development. In the
      present study, a new nano-foveolae structure verified by SEM and AFM was prepared
      by simulating the nanotubes exfoliation from anodized Ti. MC3T3-E1 preosteoblasts
      were used to investigate the effects of new nanoscale surface on cell spreading,
      proliferation, and osteogenic gene expression. The new nano-foveolae structure
      supported preosteoblast better spreading, more filopodiaes shown by SEM (4 h),
      and lower proliferation (72 h) than the smooth Ti. By two weeks, the new
      nanoscale surface induced higher expression of osteogenic markers alkaline
      phosphatase (ALP), osteopontin (OPN), osteocalcin (OCN), and collagen I (COL I)
      with real-time RT-PCR compared to the control group. The results of this study
      suggest that the new nano-foveolae structure provides a favorable surface for
      functions of bone cells.

PMID- 24738402
TI  - Electrical transport characterization of PEDOT:PSS/n-Si Schottky diodes and their
      applications in solar cells.
AB  - We demonstrate locally contacted PEDOT:PSS Schottky diodes with excellent
      rectifying behavior, fabricated on n-type Si substrates using a spin-coating
      process and a reactive-ion etching process. Electrical transport
      characterizations of these Schottky diodes were investigated by both current
      voltage (I-V) and capacitance-voltage (C-V) measurements. We found that these
      devices exhibit excellent modulation in the current with an on/off ratio of -
      10(6). Schottky junction solar cells composed of PEDOT:PSS and n-Si structures
      were also examined. From the current density-voltage (J-V) measurement of a solar
      cell under illumination, the short circuit current (I(sc)), open circuit voltage
      (V(oc)), and conversion efficiency (eta) were - 19.7 mA/cm2, - 578.5 mV, and -
      6.5%, respectively. The simple and low-cost fabrication process of the
      PEDOT:PSS/n-Si Schottky junctions makes them a promising candidate for further
      high performance solar cell applications.

PMID- 24738403
TI  - Supramolecular assembly and nanostructures of a series of luminol derivatives
      with aromatic/alkyl substituted groups in Langmuir-Blodgett films.
AB  - A series of functional luminol derivatives with aromatic and alkyl substituted
      groups has been designed and synthesized from the reaction of the corresponding
      chloride precursors with luminol. These compounds can be spread on water surface
      to form stable Langmuir films at the air-water interface. It has been found that
      UV and IR spectra confirmed the characteristic aromatic segment, imide group, and
      aromatic/alkyl substituted groups. In addition, for the interfacial assembly
      process of compounds with alkyl substituted groups, there are obvious spectral
      changes for the alkyl chains. AFM results indicated that various different
      aggregated domains may be fabricated in the transferred LB films. For all cases,
      the substituted groups in molecular structures have an important effect in
      regulating the aggregation mode and spectral changes in organized molecular
      films. The present results showed that the modified luminol derivatives may have
      potential application in functional material fields such as ECL sensor, which may
      give some insight to study the relationship between the molecular structures and
      supramolecular aggregation of amphiphiles in organized molecular films.

PMID- 24738404
TI  - Characterization and preparation of p(U-MMA-An) interpenetrating polymer network
      damping and absorbing material.
AB  - P(U-MMA-ANI) interpenetrating polymer network (IPN) damping and absorbing
      material is successfully synthesized by PANI particles served as an absorbing
      agent with the microemulsion polymerization and P(U-MMA) foam IPN network
      structure for substrate materials with foaming way. P(U-MMA-ANI) IPN is
      characterized by the compression mechanical performance testing, TG-DSC, and DSC.
      The results verify that the P(U-MMA) IPN foam damping material has a good
      compressive strength and compaction cycle property, and the optimum content of
      PMMA was 40% (mass) with which the SEM graphs do not present the phase separation
      on the macro level between PMMA and PU, while the phase separation was observed
      on the micro level. The DTG curve indicates that because of the formation of P(U
      MMA) IPN, the decomposition temperature of PMMA and the carbamate in PU
      increases, while that of the polyol segment in PU has almost no change. P(U-MMA
      ANI) IPN foam damping and absorbing material is obtained by PANI particles served
      as absorbing agent in the form of filler, and PMMA in the form of micro area in
      substrate material. When the content of PANI was up to 2.0% (mass), the
      dissipation factor of composites increased, and with the increasing of frequency
      the dissipation factor increased in a straight line.

PMID- 24738405
TI  - Fostering hydroxyapatite bioactivity and mechanical strength by Si-doping and
      reinforcing with multiwall carbon nanotubes.
AB  - The aim of the present study was to prepare resorbable hydroxyapatite (HA) based
      bone graft materials reinforced with carbon nanotubes as a way to cope with the
      inability of pure HA to resorb and its intrinsic brittleness and poor strength
      that restrict its clinical applications under load-bearing conditions. With this
      purpose, a Si-doped HA nanopowder (n-Si0.8HA) was prepared by chemical synthesis
      and used as composite matrix reinforced with different amounts of functionalized
      multiwall carbon nanotubes (MWCNTs). The effect of the added amounts of MWCNTs on
      the mechanical properties of nanocomposites and their in vitro biomineralization
      was assessed by bending strength measurements, immersing tests in simulated body
      fluid solution (SBF), scanning electron microscopy (SEM), and inductively coupled
      plasma atomic emission spectroscopy analysis (ICP-AES). The bioactivity and
      bending strength were enhanced, reaching maximum balanced values for an optimum
      addition of 3 wt.% f-MWCNTs. These results might contribute to broaden the
      potential applications of HA-based bone grafts.

PMID- 24738406
TI  - Disordered self assembled monolayer dielectric induced hysteresis in organic
      field effect transistors.
AB  - A memory device using an organic field effect transistor (OFET) with copper
      phthalocyanine (CuPc) as active material was fabricated and studied. For this
      purpose, SiO2 dielectric surface was modified with a disordered self assembled
      monolayer (SAM) of octadecyltrichlorosilane (OTS) molecule which was found to
      induce large disorder in CuPc film thereby generating more traps for charge
      carriers. Drain current-drain voltage characteristics at zero gate voltage
      exhibited large hysteresis which was not observed in OFET devices with ordered
      OTS monolayer modified and unmodified SiO2 dielectrics. The extent of hysteresis
      and drain current on/off ratio, reading voltage etc. were found to be dependent
      on the sweep rate/step voltage employed during scanning. Highest hysteresis with
      on/off ratio of about 240 was obtained for an optimum step voltage of 2 V while
      it decreased with further reduction in the same. This was attributed to the
      longer scanning time leading to release of trapped carriers during forward scan
      itself. The OFET device was found to exhibit excellent memory retention
      capability where OFF and ON current measured for about 2 hours after stressing
      the device at write and erase voltages showed good retention of on/off ratio.

PMID- 24738407
TI  - Morphology and shape control of porous silica nanostructures with dual-templating
      approaches.
AB  - There has been great interest in the synthesis of porous silica nanostructures
      because of their potential applications in catalysis, adsorption, molecular
      separation, and biomedical engineering. In this paper, we report the synthesis of
      porous silica nanostructures with varied morphologies and shapes from two-phase
      systems by using lithocholic acid (LCA) and cetyltrimethylammmonium bromide
      (CATB) or LCA and Pluronic F127 in the lower ammonia aqueous phase as dual
      directing agents and tetraethylsiloxane (TEOS) in the upper oil phase as a silica
      precursor. Porous silica spheres are formed by using LCA/CTAB as a dual directing
      agent, while silica fibers with pits are synthesized by using LCA/F127 as a dual
      directing agent. The straight-to-helical shape transition of silica fibers with
      pits can be achieved by increasing the ammonia concentration in the low aqueous
      phase.

PMID- 24738408
TI  - LaNiO3 nanotubes produced using a template-assisted method.
AB  - We have studied the experimental conditions needed to produce LaNiO3 (LNO)
      nanostructures using a template-assisted method. In this route, a mesoporous
      anodic aluminum oxide template was filled with a chemical solution that had been
      prepared with polymeric precursors route. The precursor solutions and synthesized
      samples were characterized by X-ray diffraction (XRD), thermogravimetric
      analysis, infrared spectroscopy and high-resolution scanning electron microscopy
      (HRSEM). The XRD results for the samples that were heat-treated at 700 degrees C
      revealed that these samples crystallize in a perovskite-like LaNiO3 structure.
      HRSEM images revealed that the samples prepared with different deposition times
      (0.5, 1 and 2 h) promoted the formation of LaNiO3 nanotubes with different wall
      thicknesses.

PMID- 24738409
TI  - Biosynthesis of CdS nanoparticles in banana peel extract.
AB  - Cadmium sulfide (CdS) nanoparticles (NPs) were synthesized by using banana peel
      extract as a convenient, non-toxic, eco-friendly 'green' capping agent. Cadmium
      nitrate and sodium sulfide are main reagents. A variety of CdS NPs are prepared
      through changing reaction conditions (banana extracts, the amount of banana peel
      extract, solution pH, concentration and reactive temperature). The prepared CdS
      colloid displays strong fluorescence spectrum. X-ray diffraction analysis
      demonstrates the successful formation of CdS NPs. Fourier transform infra-red
      (FTIR) spectrogram indicates the involvement of carboxyl, amine and hydroxyl
      groups in the formation of CdS NPs. Transmission electron microscope (TEM) result
      reveals that the average size of the NPs is around 1.48 nm.

PMID- 24738410
TI  - Interleaved mesoporous copper for the anode catalysis in direct ammonium borane
      fuel cells.
AB  - Mesoporous materials with tailored microstructures are of increasing importance
      in practical applications particularly for energy generation and/or storage. Here
      we report a mesoporous copper material (MS-Cu) can be prepared in a hierarchical
      microstructure and exhibit high catalytic performance for the half-cell reaction
      of direct ammonium borane (NH3BH3) fuel cells (DABFs). Hierarchical copper oxide
      (CuO) nanoplates (CuO Npls) were first synthesized in a hydrothermal condition.
      CuO Npls were then reduced at room temperature using water solution of sodium
      borohydride (NaBH4) to yield the desired mesoporous copper material, MS-Cu,
      consisting of interleaved nanoplates with a high density of mesopores. The
      surface of MS-Cu comprised high-index facets, whereas a macroporous copper
      material (MC-Cu), which was prepared from CuO Npls at elevated temperatures in a
      hydrogen stream, was surrounded by low-index facets with a low density of active
      sites. MS-Cu exhibited a lower onset potential and improved durability for the
      electro-oxidation of NH3BH3 than MC-Cu or copper particles because of the
      catalytically active mesopores on the interleaved nanoplates.

PMID- 24738411
TI  - Conductive poly(2,5-substituted aniline)s highly soluble both in water and
      organic solvents.
AB  - Highly soluble conductive polyanilines were synthesized from newly designed
      aniline derivatives: 2,5-bis(2-methoxyethoxy)aniline (2) and 2,5-bis[2-(2
      methoxyethoxy)ethoxy]aniline (3). The corresponding polyanilines, P2 and P3, were
      characterized by means of fourier transform infrared (FT-IR), thermogravimetric
      analysis (TGA), and UV-VIS-NIR spectroscopies. The electrical conductivities at
      room temperature of emeraldine salt forms of P2 (P2-ES) and P3 (P3-ES) were
      evaluated to be sigma(rt) = 2.4 x 10(-3) and 1.7 x 10(-3) S/cm, respectively. The
      length of ethylene-1,2-dioxy chains on the polyaniline scarcely affected the
      electronic conductivity. A simple modification at 2,5-positions of aniline by
      introducing 1,2-ethlenedioxy groups dramatically altered the solubility of
      polyanilines in common organic solvents and water (400 g/L for P3-ES).

PMID- 24738412
TI  - Water soluble sodium sulfate nanorods as a versatile template for the designing
      of copper sulfide nanotubes.
AB  - The present study reports the use of water soluble sodium sulfate (Na2SO4)
      nanorods as a versatile template for generation of tubular copper sulfide (CuS)
      nanostructures. The Na2SO4 nanorods were synthesized from ammonium sulfate
      (NH4)2SO4 and sodium hydroxide (NaOH), under refluxing condition. The shape and
      morphology control of the Na2SO4 nanorods were studied with respect to nature of
      surfactant used and reactant mole ratio. While, PVP mole ratio was important to
      obtain homogeneous nanorods. Uniform and stable nanotubes of CuS were than
      obtained by the dissolution of the nanorods in water. The use of simple chemicals
      for synthesis of such nanotube templates opens the prospect for wide scale
      downstream applications.

PMID- 24738413
TI  - Easily controllable synthesis of alpha-MoO3 nanobelts and MoO2 microaxletrees
      through one-pot hydrothermal route.
AB  - A mild one-pot hydrothermal route has been successfully designed to controllably
      prepare orthorhombic alpha-MoO3 nanobelts and monoclinic MoO2 microaxletrees
      respectively by adjusting the dosage of (NH4)6M07O24 x 4H2O (AHM). The products
      are characterized by X-ray diffraction (XRD), field-emission scanning electron
      microscopy (FESEM), transmission electron microscopy (TEM) and UV-visible
      absorption spectrum. The as-prepared alpha-MoO3 nanobelts, with widths of 100-400
      nm and lengths up to 30-40 microm, grow along [001] direction. The as-obtained
      MoO2 microaxletrees are assembled by countless nanolaths with the thickness of 80
      150 nm. The chemical reaction processes for the formation of MoO(x) (MoO3 and
      MoO2) phases are investigated based on the experimental phenomena. The possible
      growth mechanisms are also discussed. The band gap energies (E(g)) of the
      obtained alpha-MoO3 nanobelts and MoO2 microaxletrees are calculated to be 2.90
      and 3.72 eV, respectively. This work exhibits an effective approach in the
      selectively controlled synthesis of MoO(x) (x = 2, 3) nanomaterials via one-step
      hydrothermal strategy.

PMID- 24738414
TI  - A novel method to fabricate silicon tubular gratings with broadband
      antireflection and super-hydrophobicity.
AB  - We have developed a novel method to fabricate micro/nano structure based on the
      coherent diffraction lithography, and acquired periodic silicon tubular gratings
      with deep nano-scale tapered profiles at the top part. The optical properties of
      these tubular gratings were similar to an effective gradient-index antireflective
      surface, resulting in a broadband antireflective combining super-hydrophobic
      behavior. The mechanism of the method was simulated by rigorous coupled wave
      analysis algorithms. Then coherent diffraction lithography by use of suitable
      mask, in which periodic micro-scale circular opaque patters were distributed, was
      realized on the traditional aligner. Due to coherent diffraction, we obtained
      enough light intensity for photoresist exposure under the center of the opaque
      area in the mask together with transparent areas. The tapered line profiles and
      hollow photoresist gratings over large areas could be fabricated on the silicon
      wafer after development. The dry etching process was carried out, and high aspect
      ratio silicon tubular gratings with deep tapered profiles at the top were
      fabricated. The optical property and wettability of the structure were verified,
      proving that the proposed method and obtained micro/nano structure provide
      application potential in the future.

PMID- 24738415
TI  - Template-free hydrothermal synthesis different morphologies of visible-light
      driven BiVO4 photocatalysts.
AB  - Monoclinic BiVO4 nano- and microstructures with a diversity of well-defined
      morphologies, such as nanoplates, dendrite leaves-like structures, sub-microrods,
      and microflowers were synthesized via a template-free hydrothermal process with
      bismuth nitrate and ammonium metavanadate as metal source. The crystal
      structures, morphologies and optical properties of the as-prepared samples were
      characterized by X-ray powder diffraction (XRD), transmission electron microscope
      (TEM), scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS)
      and UV-visible absorption spectra (UV-vis). Results showed that the pH value of
      the solution and the volume of ethylenediamine have great effect on the formation
      of these unique structures. The photocatalytic activity of these as-prepared
      samples had been tested by degradation of methylene blue under visible light,
      indicating that showed good photocatalytic performance.

PMID- 24738416
TI  - Surface enhanced fluorescence from silver film substrate decorated with nanohole
      arrays.
AB  - The fluorescence enhancement effect of Rh6G molecules deposited on the silver
      film substrate decorated with nanohole arrays was investigated in this paper. The
      prepared substrate, decorated with nanohole arrays, was fabricated with the
      deposition of silver films onto the anodic aluminum oxide templates through
      magnetron sputtering method. Compared with the conventional continuous silver
      film substrate, the prepared substrate shows better enhanced effect.
      Particularly, the fluorescence enhancement factor has a relationship with the
      size and period of the nanohole arrays. The experimental observations were
      analyzed with local surface plasmon resonance model. The results of current work
      highlight the importance of strong electromagnetic coupling effect in surface
      enhanced fluorescence.

PMID- 24738417
TI  - Near-infrared luminescence from Y2O3:Eu3+, Yb3+ prepared by sol-gel method.
AB  - Eu3+ and Yb3+ codoped Y2O3 phosphors were synthesized by the sol-gel method. The
      phosphors possess absorption in the region of 300-550 nm, exhibiting an intense
      NIR emission of Yb3+ around 1000 nm, which is suitable for matching the maximum
      spectral response of c-Si solar cells. The optimum composition of Eu3+ and Yb3+
      codoped Y2O3 was (Y1.94Yb0.04Eu0.02)2O3. It is observed that two-step energy
      transfer occurs from the 5D2 level of Eu3+ situated around (466 nm) exciting two
      neighboring Yb3+ ions to the 2F5/2 level (1000 nm). The down-conversion material
      based on Eu(3+)- Yb3+ couple may have great potential applications in c-Si solar
      cells to enhance their photovoltaic conversion efficiency via spectral
      modification.

PMID- 24738418
TI  - Synthesis and photoluminescent properties of NaYF4:Eu3+ core and NaYF4:Eu3+/NaYF4
      core/shell nanocrystals.
AB  - NaYF4:Eu3+ core and NaYF4:Eu3+/NaYF4 core/shell nanocrystals (NCs) were
      synthesized via a wet chemical method. The transmission electron microscope
      photographs show that the core and core/shell nanoparticles are monodisperse and
      uniform NCs with average diameters of 22 and 26 nm respectively. The
      photoluminescence (PL) properties of the samples, including the PL excitation and
      emission spectra, and luminescent decay curves, are investigated in detail. The
      results show that the intensity of 5D2 emission relative to that of 5D0 is
      stronger in NaYF4:Eu3+/NaYF4 core/shell NCs than that in NaYF4:Eu3+ core NCs, and
      a longer decay lifetime of 5D2 is observed in core/shell samples. In addition,
      from the corrected emission spectra of 5D0, the 5D0 radiative lifetimes were
      calculated. These together with the measured decay lifetime of 5D0 emission give
      the intrinsic quantum yields of 5D0. The results were well interpreted by
      considering the surface effects.

PMID- 24738419
TI  - Enhanced photoluminescence from ordered arrays of cadmium sulfide nanotubes
      synthesized using nanoscale chemical reactors.
AB  - We report enhanced room temperature photoluminescence from ordered arrays of few
      micrometers long cadmium sulfide nanotubes fabricated using 'nanoscale chemical
      reactors' of porous alumina by a unique two-chamber synthesis without using any
      surfactants. Photoluminescence from these nanotubes is -20 times larger than that
      of nanocrystalline cadmium sulfide particles prepared by bulk mixing of the same
      reactants. However, we rule out any quantum size effect as a source of enhanced
      photoluminescence from these intentionally un-passivated nanotubes. We identify
      sulfur deficiency in these nanotubes and directional orientation of these ordered
      nanotube arrays as the main reason for its superior photoluminescence as compared
      to agglomerated nanocrystallites of CdS prepared by bulk mixing.

PMID- 24738420
TI  - Growth of ZnS nanostructures in high vacuum by thermal evaporation.
AB  - ZnS nanostructures were grown on Si substrates in high vacuum by modified thermal
      evaporation technique. Morphology, chemical composition and structural properties
      of grown ZnS nanostructures were studied using scanning electron microscope
      (SEM), X-ray diffractometer and transmission electron microscope (TEM). SEM
      studies showed that morphology of the grown structures varies with incident flux
      and source temperature. TEM studies showed that grown nanostructures are single
      crystalline in nature without structural defects such as stacking faults and
      twins. No catalytic particle was included in this growth process, and hence these
      micro and nanostructures were assumed to grow by VS mechanism.

PMID- 24738422
TI  - Preparation and characterization of fullerene (C60) amino acid nanoparticles for
      liver cancer cell treatment.
AB  - The properties of an ideal photosensitizer are water solubility, low cytotoxicity
      in the dark, high ability to produce reactive oxygen species (ROS). The
      characteristics of water-soluble fullerene (C60) amino acid nanoparticles as a
      photosensitizer were evaluated. C60 modified with l-phenylalanine (C60-phe) or
      glycine (C60-gly) was very efficient to carry out photodynamic activity leading
      to cleavage of plasmid DNA in vitro. These C60 amino acid nanoparticles were the
      most active photosensitizer against human Liver cancer cells and induced cancer
      cells apoptosis after illumination. However, these derivatives exhibited no
      significant cytotoxicity in dark. It produced diffuse intracellular fluorescence
      when 2',7'-dichlorfluorescein-diacetate (DCFH-DA) was added as an ROS probe,
      suggesting phototoxicity of these derivatives related with the generation of
      intracellular ROS. These findings indicate that these fullerene derivatives may
      be excellent candidate PDT enhancing agents.

PMID- 24738421
TI  - Refluxing synthesis, photoluminescence and binding ability to deoxyribonucleic
      acid of water-soluble rare earth ion-doped LaF3 nanoparticles.
AB  - Water-soluble rare earth ion (Ce3+, Tb3+)-doped LaF3 nanoparticles with the
      ability to bind to deoxyribonucleic acid (DNA) were prepared by the refluxing
      method in a glycerol/water mixture and characterized by X-ray diffraction (XRD),
      transmission electron microscopy (TEM), photoluminescence (PL) spectra, and so
      on. The obtained LaF3:Ce3+, LaF3:Tb3+ and LaF3:Ce3+, Tb3+ nanoparticles are well
      crystallized with a hexagonal structure and composed of spherical particles with
      an average size from 11 to 19 nm. The as-prepared samples can be dispersed into
      water to form a colloidal solution. Under ultraviolet (UV) light irradiation, the
      emission lines of Tb3+ in the co-doped LaF3:Ce3+, Tb3+ are evidently strengthened
      compared to those in the single-doped LaF3:Tb3+ nanoparticles, which is due to
      the energy transfer from Ce3+ to Tb3+ ions in the LaF3:Ce3+, Tb3+ samples. The
      biological experiment confirms that the water-soluble LaF3:Ce3+, Tb3+
      nanoparticles can be bonded to the DNA molecules and emit visible light under UV
      irradiation. These luminescent nanoparticles could be used similarly to ethidium
      bromide (EtBr), which has been used extensively as a DNA staining reagent. The
      advantage that LaF3:Ce3+, Tb3+ nanoparticles have lower toxicity than EtBr makes
      them a potential reagent instead of EtBr in the DNA staining in biological
      experiments.

PMID- 24738423
TI  - Nanopharmaceutical approach of epiisopiloturine alkaloid carried in liposome
      system: preparation and in vitro schistosomicidal activity.
AB  - Schistosomiasis is a neglected tropical disease caused by blood flukes of the
      genus Schistosoma. This disease control has been widely made by praziquantel
      reference drug, but resistance to this drug has already been found. There has
      been the finding of an imidazole alkaloid in jaborandi leaves-epiisopiloturine,
      which has known activity against adult, young and egg forms of Schistosoma
      mansoni. This alkaloid is an apolar molecule with difficult solubility;
      therefore, the liposomal structure of epiisopiloturine was proposed. Liposomes
      are carrying structures of drugs that may enhance solubility of compounds such as
      epiisopiloturine. In this work, we report in vitro epiisopiloturine-loaded
      liposomes effect formed by different concentrations of lipids 9:1 (weight ratio)
      dipalmitoylphosphatidylcholine:cholesterol and 8:2 (weight ratio)
      dipalmitoylphosphatidylcholine:cholesterol. Results have showed that
      epiisopiloturine extraction and isolation have been successful through high
      performance liquid chromatography-HPLC and its purity confirmed through mass
      spectrometry has showed 287 Da molecular mass. Formulations from 9:1
      DPPC:cholesterol and 8:2 DPPC:cholesterol with loaded EPI (300 microg/ml) have
      killed parasites at 100% after incubation 96 h and 120 h, respectively. Confocal
      microscopy employed to observe morphological alterations in the tegument of adult
      form of Schistosoma mansoni. Details from interaction, between epiisopiloturine
      and liposome, have been achieved by semi-empirical AM1 calculations, which have
      showed that epiisopiloturine inside is more stable than the outside form, at
      least 10 kcal. This is first time that schistosomicidal activity has been
      reported for epiisopiloturine-loaded into liposome.

PMID- 24738424
TI  - Preparation of liposomal nanoparticles incorporating terbinafine in vitro drug
      release studies.
AB  - Terbinafine hydrochloride (TBH) (E)-N-(6,6-dimethyl-2-hepten-4-inyl)-N-methyl-1
      naphthaline-methanamine(-hydrochloride) is an effective antifungal agent already
      existing on the market in the form of topical formulations. The present study
      deals with the preparation and physicochemical characterization (size,
      polydispersity, zeta-potential) of 1,2-Diacyl-sn-glycero-3-phosphocholine (EggPC)
      incorporating TBH in two different dispersion media (tris-buffered saline (TBS)
      of pH 7.4 or in phosphate buffer solution (PS) of pH 5.5) in order to investigate
      how pH of dispersion media affects the incorporation efficiency of TBH into
      liposomes. There were further prepared three Carbopol 934 hydrogels of different
      concentrations (0.5, 1 and 2%) and their viscosity was measured and evaluated.
      Moreover, the in vitro drug release from three liposomal gels was studied, in
      order to investigate the ability of liposomes to act as carriers for TBH in a
      gel. All formulations were found to retain their original physicochemical
      properties at least for three weeks. These early studies on the release kinetics
      from liposomal gel show that Korsmeyer-Peppas model could be the best fitted
      model concerning the TBH release profile and could be supported biophysically
      from extended Derjaguin-Landau-Verwey-Overbeek (DLVO) theory.

PMID- 24738425
TI  - Oxidative stress and acute changes in murine brain tissues after nasal
      instillation of copper particles with different sizes.
AB  - We aim to investigate the biological effects of copper particles on the murine
      brain and their underlying mechanism after nasal instillation of copper
      particles. We choose different sizes and different concentrations of copper
      nanoparticles for mice intranasal use. Within one week, the mice were sacrificed.
      Pathological lesions of glial cells were detected by immunohistochemical assay.
      Immunohistochemical assay reveals that glial fibrillary acidic protein (GFAP)
      increased significantly in all experimental groups, especially in nanocopper
      groups. The ultrastructure of nerve cells was observed through TEM, whose results
      show that there were chromatin congregation and mitochondria shrinkage in the
      olfactory cells, and that there was increase of endoplasmic reticulum and
      disassociation of endoplasmic reticulum ribosomes in hippocampus, particularly in
      the nanocopper-groups. Oxidative stress indexes were determined with colorimetric
      methods. There was no significant increase in the antioxidative enzymes (GPX,
      GST, SOD) in brain tissues; however, significant increase of malondiadehyde (MDA)
      contents was only found in the Cu nanoparticle-exposed mice at the high dose of
      40 mg per kg body weight. Based on the investigation into the biological effects
      of copper nanoparticles (23.5 nm) after intranasal instillation to the mice, we
      have found that copper particles can indeed enter into the olfactory bulb and
      then the deeper brain. The inhalation of high dose copper nanoparticles can
      induce severer lesions of brain in the experimental mice. The underlying
      mechanism of copper nanoparticles causing severe brain damage bears little
      connection with oxidative stress.

PMID- 24738426
TI  - Engineering bamboo-type TiO2 nanotube arrays to enhance their photocatalytic
      property.
AB  - Bamboo-type TiO2 nanotube arrays with high surface area can be synthesized by
      alternating voltage (AV) anodization for their important use as photocatalytic
      medium. Their morphologies are highly dependent on preparation parameters
      including anodization time and electrolyte composition. Minimum time of high
      voltage steps required for forming desired bamboo ridge spacing on these
      nanotubes can be calculated from current-time profiles recorded during
      potentiostatic anodization at the voltage. Water content in NH4F-containing
      ethylene glycol (EG) electrolytes is optimized simply from analyses of current
      transients or current-voltage relations for anodization in EG electrolytes with
      different amount of water, in order to achieve efficient electrochemical growth
      of TiO2 nanotubes for large ridge density and long tube length. Two types of
      bamboo-type TiO2 nanotubes with the same length of 5.46 microm but different
      ridge spacing are synthesized for photocatalytic degradation of methylene blue
      (MB) under UV radiation. Both of the bamboo-type nanotube arrays show improved
      photo catalysis compared to smooth TiO2 nanotubes of the same length, due to
      their larger surface area favorable for heterogeneous catalytic processes. In
      particular, the apparent rate constant of photocatalytic degradation on bamboo
      type nanotubes is up to 29.4% higher than that for degradation on smooth ones.

PMID- 24738427
TI  - Catalytic performance of functionalized IRMOF-3 for the synthesis of glycerol
      carbonate from glycerol and urea.
AB  - A functionalized isoreticular metal organic framework material, F-IRMOF-3, having
      a quaternary ammonium group was prepared by fast precipitation and solvothermal
      method. The synthesized MOFs exhibited good catalytic performance in the
      synthesis of glycerol carbonate (GC) from glycerol and urea. F-IRMOF-3 having a
      larger alkyl chain structure and a more nucleophilic counter anion than the
      synthesized congeners, exhibited better reactivity in the synthesis of GC. The
      introduction of a ZnO defect into the F-IRMOF-3 structure by fast precipitation
      was more advantageous for the glycerolysis of urea than the conventional
      solvothermal method because of the incorporation of acid-base bifunctional active
      sites by the former method. The effects of reaction parameters such as
      temperature, reaction time, catalyst loading, and degree of vacuum on the
      reactivity were also investigated. The F-IRMOF-3 catalyst can be easily recovered
      and reused without considerable loss of its initial activity.

PMID- 24738428
TI  - Multi-walled carbon nanotube with multivacancy defects: porous structure and Pt
      decoration.
AB  - This study reports on the morphological characteristics of multi-walled carbon
      nanotube with multi-vacancy defects (MWCNT-MD) of carbon atoms and shows the
      potential of MWCNT-MD as a support for metal deposition by decorating Pt
      nanoparticles (NPs). Multi-carbon vacancies on MWCNT were introduced by oxidizing
      cobalt oxide-decorated MWCNT at 250 degrees C for 6 h in air by means of carbon
      gasification reaction, resulting in holes and thinned walls on MWCNT. It was
      revealed that creating multivacancy defects led to the increase of specific
      surface area from 107 to 152 m2/g and pore size in the range of 5-8 nm increased
      on MWCNT compared with that of pristine MWCNT. 30 wt.% Pt was decorated on MWCNT
      MD by impregnation method to investigate the effect of carbon vacancies on the
      degree of Pt dispersion, and the presence of Pt metal was confirmed by X-ray
      diffraction. Transmission electron microscopy images clearly displayed that Pt
      NPs with average particle size of 2.8 nm were evenly dispersed on the defective
      site of holes and thinned walls. This study is clear evidence showing that
      defective sites of MWCNT are active and good anchor site for metal decoration.

PMID- 24738429
TI  - Low-temperature growth of aligned ZnO nanorods: effect of annealing gases on the
      structural and optical properties.
AB  - Aligned ZnO nanorods were grown on ZnO/Si substrate via simple aqueous solution
      process at low-temperature of - 65 degrees C by using zinc nitrate and
      hexamethylenetetramine (HMTA). The detailed morphological and structural
      properties measured by FESEM, XRD, EDS and TEM confirmed that the as-grown
      nanorods are vertically aligned, well-crystalline possessing wurtzite hexagonal
      phase and grown along the [0001] direction. The room-temperature
      photoluminescence spectrum of the grown nanorods exhibited a strong and broad
      green emission and small ultraviolet emission. The as-prepared ZnO nanorods were
      post-annealed in nitrogen (N2) and oxygen (O2) environments and further
      characterized in terms of their morphological, structural and optical properties.
      After annealing the nanorods exhibit well-crystallinity and wurtzite hexagonal
      phase. Moreover, by annealing the PL spectra show the enhancement in the UV
      emission and suppression in the green emission. The presented results demonstrate
      that simply by post-annealing process, the optical properties of ZnO
      nanostructures can be controlled.

PMID- 24738430
TI  - Luminescent properties of BaAl12O19:Tb, Dy phosphors prepared by sol-gel method.
AB  - BaAl12O19:Tb, Dy phosphor was prepared by the sol-gel technique using citric acid
      as a complextant. XRD was used to characterize the relevant crystallization
      behavior of the phosphor. The luminescence properties and energy transfer between
      Tb3+ and Dy3+ were investigated. The results revealed that energy transfer exists
      between Dy3+ and Tb3+ at appropriate Tb3+ concentrations. The emission intensity
      of Tb3+ increases and energy transfer happens from Dy3+ to Tb3+ ions at the
      higher content of Tb3+ when Tb3+ and Dy3+ ions were co-doped. BaAl12O19 phosphors
      doped with Tb3+ or Dy3+ ions only were studied to compared with BaAl12O19:Tb, Dy
      phosphors. The results showed that the maximum excitation peak of BaAl12O19:Tb is
      240 nm and the emission spectrum consists of four peaks at 490, 545, 590, and 625
      nm, originating from 5D4 --> 7FJ (J = 6, 5, 4, 3) transitions of Tb3+ ion,
      respectively. The excitation peaks of BaAl12O19:Dy are at 291, 324 nm and the
      emissions of Dy3+ are at 370, 447 and 578 nm, originating from 4F9/2 --> 6P5/2,
      4F9/2 --> 6H15/2 and 4F9/2 --> 6H13/2 transitions of Dy3+ ion, respectively.

PMID- 24738431
TI  - Synthesis and luminescence properties of NaSrPO4:Eu2+, Tb3+, Mn2+ for WLED.
AB  - In order to obtain a single-host-white-light phosphor used for near ultraviolet
      (NUV) light emitting diodes (LEDs), the NaSrPO4:Eu2+, Tb3+, Mn2+ powder samples
      were synthesized via a high temperature solid-state reaction. XRD investigation
      shows a single phase. Energy transfer processes is discussed by analyzing the
      photoluminescence (PL) and photoluminescence excitation (PLE) spectra. White
      light emitting was observed upon the excitation of a wide range of ultraviolet
      (UV) wavelengths. The emission spectra are made up of blue, green and red
      emissions from Eu2+, Tb3+ and Mn2+ ions, respectively. The color shift is
      insignificant when altering the excitation wavelength from 260 nm to 400 nm. This
      indicates that the phosphor could exhibit good color stability when used in
      combination with a NUV LED.

PMID- 24738432
TI  - Hydrothermal synthesis and photoluminescent properties of rod-shape assemblies of
      LaBO3:Eu3+ nanocrystals.
AB  - Uniform and assembled LaBO3 nanocrystals have been successfully synthesized via a
      facile hydrothermal method. These assemblies exhibit a rod-shape morphology and
      each of them consists of small LaBO3 nanocrystals which are tightly attached
      together. The phase, surface and morphology of these assemblies have been
      characterized. A possible assembly mechanism of such morphology is also proposed
      through investigation on the formation process. Photoluminescent spectra suggest
      that these assemblies doped with Eu3+ can give stronger red emissions than the
      orange one due to its aragonite structure. Such emission has been explained by
      the Judd-Ofelt theory. It is expected that these well-defined LaBO3 assemblies
      could find applications in future luminescent displays and lamps.

PMID- 24738433
TI  - Ordered hexagonal mesoporous aluminosilicates with low Si/Al ratio: synthesis,
      characterization, and catalytic application.
AB  - Ordered hexagonal mesoporous aluminosilicates with lower Si/Al ratio below 5 have
      been successfully synthesized via the co-assembly of preformed aluminosilicate
      precursors with Gemini surfactant [C12H25N+(CH3)2(CH2)6N+(CH3)2C12H25] x 2Br(-)
      as the template. Powder X-ray diffraction, transmission electron microscopy,
      scanning electron microscopy, N2 adsorption-desorption isotherm measurements,
      Fourier transform infrared spectroscopy, 27Al nuclear magnetic resonance,
      thermogravimetric analysis, and temperature-programmed desorption of
      cyclohexylamine are employed to characterize the resulting samples. The phenol
      alkylation reaction is carried out to evaluate their catalytic performances.
      These studies indicate that the sample with a low Si/Al ratio of 3 still retains
      a highly ordered hexagonal mesoporous structure. And it also possesses the
      highest acidity of 0.96 mmol among the samples with lower Si/Al ratios below 5
      due to its higher specific surface area together with more content of
      tetrahedrally coordinated Al in the framework. The catalytic tests confirm that
      the acidity of the samples plays a key role in determining their catalytic
      performances.

PMID- 24738434
TI  - Flagella interacting with a carbon nanowire with the variation of time and
      initial temperature.
AB  - The system proposed consists of a flagellum relaxing around a static carbon
      nanowire to mimics behavior of a natural flagellum moving with damped harmonic
      motion along a wire under van der Waals and electrostatic forces. This flagellum
      is composed of a C20 nanosphere with different sizes of his tail formed by
      hydrocarbons. The thermodynamic properties such as molar entropy variation, as
      well as molar heat dissipation, efficiency and speed were obtained to evaluate
      which system is most stable by using the variable temperature. This system has a
      number of carbon atoms ranging from 103-110, with a maximum of 300 ps for each
      simulation. We had simulated molar entropy variation, energies and efficiency
      changing with time and initial temperature. The results indicate that among the
      systems studied, the flagellum with five carbon atoms achieved greater stability
      and better results in this search.

PMID- 24738435
TI  - The effect of growth temperature variation on partially bismuth filled carbon
      nanotubes synthesis using a soft semi-metallic template.
AB  - The dewetting of a low melting point metal thin film deposited on silicon
      substrates was studied. The experimental results suggest that the change in the
      growth temperature affects the nanostructures that form. Based on the
      experimental results, the temperature which yielded the smallest features for the
      growth of nanotubes is determined. The mechanism by which these nano-templates
      become an efficient seeds for the growth of the carbon nanotubes is discussed.
      The partial bismuth filling inside the CNTs was optimized. Based on the results,
      a schematic growth model for better understanding of the process parameters has
      also been proposed.

PMID- 24738436
TI  - Influence of nanoparticle concentration on thermo-physical properties of CuO
      propylene glycol nanofluids.
AB  - Experiments were performed on the preparation and characterization of CuO
      propylene glycol nanofluids. The influence of nanoparticle concentration and
      temperature on nanofluid viscosity reveals existence of a range of nanoparticle
      concentration and temperature in which the viscosity of nanofluid is lower than
      that of propylene glycol, possibly due to interactions between nanoparticles and
      propylene glycol. A temperature-independent, thermal conductivity enhancement of
      38% was obtained for nanoparticle concentration of 1.5 vol% over a temperature
      range of 10-60 degrees C. We believe that particle clustering contributes to the
      thermal conductivity enhancement in CuO-propylene glycol nanofluids.

PMID- 24738437
TI  - Polymer-templated electrodeposition of Ag nanosheets assemblies array as
      reproducible surface-enhanced Raman scattering substrate.
AB  - Position-configurable, reproducible, vertically aligned nanosheets assemblies
      (ANAs) arrays are fabricated by polymer-templated electrodeposition method at
      room temperature. Here, nanoimprint lithography is utilized to fabricate polymer
      template on the fluorine-doped tin oxide substrate for the purpose of evenly
      tuning the location of Ag nanostructures. Subsequently, vertically aligned ANAs
      can be achieved at the bottom of each hole via electrodeposition in a mixed
      aqueous solution of AgNO3 and citric acid. To obtain uniform ANAs array, we have
      systematically investigated the factors that influenced the electrodeposition. It
      was found that the formation of uniform ANAs arrays is strongly depended on the
      seeding layer, citric acid concentration, electrodeposition potential and time.
      The as-synthesized ANAs array exhibited a remarkable SERS activity and Raman
      signal reproducibility to rhodamine 6G, a concentration down to 10(-13) M can be
      identified. Our results revealed that the ANAs array is a highly desirable
      candidate as the reliable enhancer for high performance SERS analysis.

PMID- 24738438
TI  - Sol-gel-Derived highly sensitive optical oxygen sensing materials using Ru(II)
      complex via covalent grafting strategy.
AB  - The preparation and oxygen sensing properties of Ru(ll) covalently-grafted and
      physically-incorporated silica based hybrid materials by sol-gel technique are
      described in this article. The Ru(II) complexes are successfully grafted onto the
      backbone of the silica via the condensation reaction of the tetraethoxysilane and
      the functionalized Ru(II) complex 2-[4'-{3-(Triethoxysilyl)propyl}phenyl]imidazo
      [4,5-f]-1,10-phenanthroline that contains the hydrolysable tri-alkoxylsilyl
      group. The luminescence quenching of Ru(II) complex by oxygen within the silica
      matrix is efficient. The oxygen quenching sensitivity of the covalently-grafted
      sample is higher than that of the physically-incorporated one due to the strong
      Si-CH2 bond that is useful to prolong the excited state lifetimes and enhance the
      photobleaching of the luminophore. The downward oxygen sensing Stern-Volmer plots
      can be well fitted using the Demas two-site model and the Lehrer model due to the
      heterogeneous distribution of the Ru(ll) complex within the sol-gel derived
      silica.

PMID- 24738439
TI  - Fabrication of ordered poly(methyl methacrylate) nanobowl arrays using SiO2
      colloidal crystal templates.
AB  - A simple approach is presented for the fabrication of poly(methyl methacrylate)
      (PMMA) nanobowl arrays over cm2 areas using SiO2 colloidal crystal templates.
      SiO2 colloidal crystal templates were prepared on a clean glass substrate by self
      assembled SiO2 spheres of 410 nm in diameter. The air between the silica spheres
      was filled by the superfluous monomer of PMMA that can be subsequently
      polymerized. After infiltration, the SiO2-PMMA templates were immersed in a 3 wt%
      hydrofluoric acid (HF) aqueous solution. After 24 h, silica spheres were etched
      and a free-standing nanobowl sheet was obtained. The size of the nanobowls could
      be controlled by the size of the SiO2 spheres and the area of the nanobowl sheet
      could be altered by the size of the glass substrate.

PMID- 24738440
TI  - Immobilization of alkaline phosphatase on solid surface through self-assembled
      monolayer and by active-site protection.
AB  - Retaining biological activity of a protein after immobilization is an important
      issue and many studies reported to enhance the activity of proteins after
      immobilization. We recently developed a new immobilization method of enzyme using
      active-site protection and minimization of the cross-links between enzyme and
      surface with a DNA polymerase as a model system. In this study, we extended the
      new method to an enzyme with a small mono-substrate using alkaline phosphatase
      (AP) as another model system. A condition to apply the new method is that masking
      agents, in this case its own substrate needs to stay at the active-site of the
      enzyme to be immobilized in order to protect the active-site during the harsh
      immobilization process. This could be achieved by removal of essential divalent
      ion, Zn2+ that is required for full enzyme activity of AP from the masking
      solution while active-site of AP was protected with p-nitrophenyl phosphate
      (pNPP). Approximately 40% of the solution-phase activity was acquired with active
      site protected immobilized AP. In addition to protection active-site of AP, the
      number of immobilization links was kinetically controlled. When the mole fraction
      of the activated carboxyl group of the linker molecule in self-assembled
      monolayer (SAM) of 12-mercaptododecanoic acid and 6-mercapto-1-ethanol was
      varied, 10% of 12-mercaptododecanoic acid gave the maximum enzyme activity.
      Approximately 51% increase in enzyme activity of the active-site protected AP was
      observed compared to that of the unprotected group. It was shown that the concept
      of active-site protection and kinetic control of the number of covalent
      immobilization bonds can be extended to enzymes with small mono-substrates. It
      opens the possibility of further extension of the new methods of active-site
      protection and kinetic control of immobilization bond to important enzymes used
      in research and industrial fields.

PMID- 24738441
TI  - Organic-inorganic hybrids of imidazole complexes of zinc (II) for catalysts in
      the glycerolysis of urea.
AB  - Bis(alkylimidazole) complexes of zinc, (RIm)2ZnX2, were prepared by a metal
      insertion reaction. The synthesized (RIm)2ZnX2 exhibited good catalytic
      performance during synthesis of glycerol carbonate (GC) from glycerol and urea.
      (HEIm)2ZnCl2 with a hydroxyl group exhibited the highest GC yield during
      glycerolysis of urea owing to incorporation of acid-base bifunctional active
      sites. (EIm)2ZnX2 catalysts based on different halide anions showed increased
      reactivity as Cl- < Br- < I-, which is the order of nucleophilicity. The effects
      of reaction parameters such as temperature, reaction time, catalyst loading, and
      degree of vacuum on the reactivity were also investigated.

PMID- 24738442
TI  - Homopiperazine grafted mesoporous silicas from rice husk ash for CO2 adsorption.
AB  - Chloro-functionalized mesoporous MCM-41, SBA-15, MCM-48 and KIT-6 were
      synthesized by co-condensation of 3-chloropropyl-trimethoxy-silane (CPTMS) and
      rice husk ash sodium silicate solution, which is subsequently grafted with a
      heterocyclic amine, homopiperazine (HPZ). X-ray powder diffraction and BET
      analysis of the chloro-functionalized mesoporous silicas confirmed the similarity
      between their structural properties and those obtained from conventional silica
      sources. CO2 adsorption studies of all HPZ-grafted mesoporous silicas exhibited 8
      10 wt% of adsorption capacity and are found to be selective, recyclable and
      thermally stable. Here, the CO2 adsorption reaction is via the traditional
      carbamate mechanism. The presence of both secondary and tertiary amine in HPZ
      influences the high CO2 adsorption capacity. Hence, these HPZ-grafted mesoporous
      silicas could contribute to CO2 capture as a green, tunable, selective and
      efficient sorbent.

PMID- 24738443
TI  - Preparation of single phase Zn2TiO4 spinel from a new ZnTi layered double
      hydroxide precursor.
AB  - A single-source ZnTi-layered double hydroxide precursor was used to prepare
      single phase Zn2TiO4. This approach involves two steps: the calcination of a ZnTi
      layered double hydroxide precursor and selective leaching zinc oxide from the
      resultant calcined products. The materials were characterized by X-ray
      diffraction (XRD), scanning electron microscope (SEM) thermogravimetric and
      differential thermal analysis (TG-DTA), transmission electron microscope (TEM),
      surface area measurement and UVvis diffuse reflection spectroscopy. The results
      indicated that a single phase Zn2TiO4 could be successfully obtained from a ZnTi
      layered double hydroxide precursor at a relatively low temperature in short
      calcination time. The TEM and SEM show that the diameter of Zn2TiO4 particles
      prepared at 900 degrees C is in the range of 20-100 nm and smaller than that
      prepared by the solid-state method. UV-Vis diffuse reflection spectroscopy
      demonstrates that the material has an energy bandgap around 3.7 eV.

PMID- 24738444
TI  - Adsorption of methyl violet onto mesoporous MCM-48 from aqueous solution.
AB  - In this study, hexadecyltrimethyl ammonium bromide and triblock poly(ethylene
      oxide)-poly(propylene oxide)-poly(ethylene oxide) were used as co-templates and
      tetraethoxysilane was used as silica source to synthesize mesoporous MCM-48,
      which was employed to adsorb methyl violet dye from water. The prepared MCM-48,
      after calcination at 550 degrees C, was found to have a high surface area of 1072
      m2/g and a pore volume of 1.08 cm3/g. The MCM-48 adsorption of methyl violet in
      aqueous solution was studied using UV-visible spectrophotometry. Experimental
      conditions, including initial pH of sample solution, initial concentration, MCM
      48 amount, adsorption time and temperature, were also investigated. Results
      showed that the adsorption behavior could well be depicted by Langmuir equations
      and pseudo-second-order kinetic model. The maximum adsorption capacity of 193.82
      mg/g was obtained at 20 degrees C. The values for thermodynamic parameters
      deltaG0, deltaS0 and deltaH0 were all negative, showing that the MCM-48
      adsorption of methyl violet was spontaneous and exothermic.

PMID- 24738445
TI  - Structure and electromagnetic properties of single-crystalline Fe3O4 hollow
      nanospheres.
AB  - Magnetite (Fe3O4) hollow nanospheres with an average diameter of 300 nm and an
      average shell thickness of 40 nm were synthesized by a surfactant-free
      solvothermal reduction method, and their structure and electromagnetic (EM)
      properties were investigated. The Fe3O4 hollow nanospheres showed single
      crystalline features along the [111] crystal growth direction and a ferrimagnetic
      behavior at room temperature. The Fe3O4 hollow nanosphere/paraffin composites
      exhibited a flatter response in the real complex relative permittivity (epsilon')
      and a lower value of -0.5 in the imaginary complex relative permittivity
      (epsilon") in comparison with other Fe3O4-based nanomaterials because of the
      enhanced electrical resistivity. Their imaginary complex relative permeability
      (mu") displayed a resonance peak at -4 GHz and a negative value up to -0.03 in
      the 17.2-18 GHz range due to the dissipation of EM energy in the cavity of the
      hollow nanospheres. Their reflection loss (RL) exceeded -10 dB from 3.1 to 10.1
      GHz at a thickness of 2.6-5 mm and attended an optimal value of -43.5 dB at 4 GHz
      at 5 mm thickness as a result of an effective complementation between the
      dielectric and magnetic losses.

PMID- 24738446
TI  - Encapsulation of the antimicrobial and immunomodulator agent nitazoxanide within
      polymeric micelles.
AB  - Nitazoxanide (NTZ) is a highly hydrophobic nitrothiazolyl-salicylamide that
      displays antimicrobial activity against a variety of parasites, anaerobic
      bacteria and viruses. More recently, its effectiveness in the pharmacotherapy of
      chronic hepatitis, the leading cause of liver cirrhosis and hepatocellular
      carcinoma (HCC), has been reported. On the other hand, the extremely low aqueous
      solubility of the drug challenges its administration by different routes. The
      present work explored for the first time the encapsulation of NTZ within
      pristine, lactosylated and mixed poly(ethylene oxide)-poly(propylene oxide) (PEO
      PPO) polymeric micelles (PMs) of different architectures, molecular weights and
      hydrophilic-lipophilic balance (HLB) as a strategy to improve its aqueous
      solubility and to potentially target it to the liver parenchyma. The solubility
      was increased up to 609 times. The drug encapsulation modified the self
      aggregation pattern of the different amphiphiles, resulting in a sharp growth of
      the micellar size. The encapsulation capacity of the lactosylated derivatives was
      smaller than that of the pristine counterparts, though the development of mixed
      PMs that combine a highly hydrophilic lactosylated amphiphile (e.g., poloxamer
      F127 or poloxamine T1107) that forms the micellar template and a more hydrophobic
      unmodified poloxamine (T904) that increases the hydrophobicity of the core
      resulted in the synergistic encapsulation of the drug and a substantial increase
      of the physical stability over time. Overall findings confirmed the extremely
      great versatility of the poloxamer/poloxamine mixed self-assembly systems as
      Trojan nanocarriers for the encapsulation of NTZ towards its targeting to the
      liver.

PMID- 24738447
TI  - Shaping of mesoporous AISBA-15 as cylindrical nano reactor for tertiary
      butylation of phenol.
AB  - Mesoporous AISBA-15 with different n(Si)/n(Al) ratios (45, 136 and 215) in the
      powder (P) form were synthesized by hydrothermal technique. The powder materials
      were shaped into cylindrical extrudates (Ex) by compounding with additives such
      as bentonite (binder) and methylcellulose (plasticizer). The AISBA-15 materials
      were characterized by XRD, N2 adsorption, AAS, 27Al MAS-NMR and thermogravimetric
      analysis. The orderly growth of AISBA-15 is evidenced by its XRD patterns. The
      surface area and pore volume of AISBA-15 catalysts were around 950 m2/g and 1.3
      cm3/g respectively. A decrease in surface area and pore volume were observed for
      AISBA-15 (Ex) materials in comparison to AISBA-15 (P) materials. This may be due
      to partial blocking of pore entry and surface area coverage of additives during
      the shaping of extrudates. Vapor phase alkylation of phenol with tert-butanol was
      carried out over AISBA-15 (P) and AISBA-15 (Ex) catalysts and the results
      revealed that both powder and extrudate samples showed similar activity for
      phenol conversion. The activity of AISBA-15 catalysts follows the order: AISBA-15
      (45) > AISBA-15 (136) > AISBA-15 (215) for both powder and extrudate forms. The
      major products were 2-tert-butylphenol (2-TBP), 4-tert-butylphenol (4-TBP) and
      2,4-di-tert-butylphenol (2,4-DTBP). The selectivity to para product is much
      higher than other products. The catalyst exhibited steady conversion, and
      deactivation by coke formation of the catalyst is much reduced in AISBA-15
      materials.

PMID- 24738448
TI  - Preparation and characterization of mesoporous Ag/VO(x)-TiO2 employed for
      catalytic hydroxylation of benzene.
AB  - The V-based complex oxides were found to exhibit good catalytic reactivity for
      the selective oxidation of benzene to phenol. In order to understand the effect
      of the catalyst on the reaction, a series of Ag/VO(x)-TiO2 catalysts with
      different Ag loadings were prepared. Data from the X-ray diffraction (XRD), N2
      adsorption isotherms, scanning electron microscopy (SEM), transmission electron
      microscopy (TEM), H2 temperature-programmed reduction (H2-TPR), and X-ray
      photoelectron spectroscopy (XPS) showed the formation of complex oxides with
      phases of silver and vanadates, and the increased redox ability of vanadium
      species. The results from H2-TPR revealed that the addition of Ag promoted the
      reduction of vanadium species in the complex catalysts. The presence of Ag and
      Ag+ ions at the catalyst surface were proved independently by XPS measurements.
      The Ag and Ag+ ions also effectively strengthened the thermostability of the
      Ag/VO(x)-TiO2 catalyst, and the Ag species also made a strong contribution to the
      monodispersion of vanadium on the surface of the TiO2 carrier. The reactivity for
      the selective oxidation of benzene was evaluated by using a liquid-phase reaction
      unit, and was correlated with the surface redox property of the catalysts.

PMID- 24738449
TI  - Current safety practices in nano-research laboratories in China.
AB  - China has become a key player in the global nanotechnology field, however, no
      surveys have specifically examined safety practices in the Chinese nano
      laboratories in depth. This study reports results of a survey of 300
      professionals who work in research laboratories that handle nanomaterials in
      China. We recruited participants at three major nano-research laboratories (which
      carry out research in diverse fields such as chemistry, material science, and
      biology) and the nano-chemistry session of the national meeting of the Chinese
      Chemical Society. Results show that almost all nano-research laboratories
      surveyed had general safety regulations, whereas less than one third of
      respondents reported having nanospecific safety rules. General safety measures
      were in place in most surveyed nano-research laboratories, while nanospecific
      protective measures existed or were implemented less frequently. Several factors
      reported from the scientific literature including nanotoxicology knowledge gaps,
      technical limitations on estimating nano-exposure, and the lack of nano
      occupational safety legislation may contribute to the current state of affairs.
      With these factors in mind and embracing the precautionary principle, we suggest
      strengthening or providing nanosafety training (including raising risk awareness)
      and establishing nanosafety guidelines in China, to better protect personnel in
      the nano-workplace.

PMID- 24738450
TI  - Effects of reducing temperatures on the hydrogen storage capacity of double
      walled carbon nanotubes with Pd loading.
AB  - The effects of different temperatures on the hydrogen sorption characteristics of
      double-walled carbon nanotubes (DWCNTs) with palladium loading have been
      investigated. When we use different temperatures, the particle sizes and specific
      surface areas of the samples are different, which affects the hydrogen storage
      capacity of the DWCNTs. In this work, the amount of hydrogen storage capacity was
      determined (by AMC Gas Reactor Controller) to be 1.70, 1.85, 2.00, and 1.93 wt%
      for pristine DWCNTS and for 2%Pd/DWCNTs-300 degrees C, 2%Pd/DWCNTs-400 degrees C,
      and 2%Pd/DWCNTs-500 degrees C, respectively. We found that the hydrogen storage
      capacity can be enhanced by loading with 2% Pd nanoparticles and selecting a
      suitable temperature. Furthermore, the sorption can be attributed to the chemical
      reaction between atomic hydrogen and the dangling bonds of the DWCNTs.

PMID- 24738452
TI  - Field emission characteristics of regular arrays of carbon nanotubes.
AB  - The developments of electronic devices based on micron-sized vacuum electron
      sources during the last decades have triggered intense research on highly
      efficient carbon based thin film electron emitters. The synthesis of massive
      arrays of carbon nanotubes that are oriented on patterned Fe catalyst deposited
      on quartz substrates is reported. The well-ordered nanotubes can be used as
      electron field emission arrays. Scaling up of the synthesis process should be
      entirely compatible with the existing semiconductor processes, and should allow
      the development of nanotubes devices integrated into future technology. The
      emission from carbon nanotubes array is explained by Fowler-Nordheim tunneling of
      electrons from tip-like structures in the nanometer range, which locally amplify
      the applied field by the field enhancement factor beta. We found that the low
      pressure chemical vapour deposition (LPCVD) system can produce nanotubes capable
      of excellent emission currents at lower voltages. The carbon nanotubes array
      shows good field emission with turn on field E(alpha) = 1.30 V/microm at the
      current density of 3.50 mA/cm2 with enhancement factor beta = 1.22 x 10(2).

PMID- 24738451
TI  - Synthesis of LiYF4:Yb, Er upconversion nanoparticles and its fluorescence
      properties.
AB  - LiYbF4:Yb, Er nanoparticles have been successfully synthesized by thermal
      decomposition of multiple trifluoroacetic acid salts. The SEM and TEM results
      show the size of the LiYF4:Yb, Er nanoparticles is about 100 nm in diagonal line,
      and the morphology of the LiYF4:Yb, Er nanoparticles is highly uniform with
      octahedral structure. Under the excitation of 980 nm, the LiYF4:Yb, Er
      nanoparticles have higher upconversion luminescence efficiency compared with that
      of NaYF4:Yb, Er. The results indicate that the as-prepared LiYbF4:Yb, Er
      nanoparticles may have potential applications in bio-probes and displays.

PMID- 24738453
TI  - [Progress in the treatment of female sexual dysfunction].
AB  - With the progress of society and development of sexual medicine, the therapeutic
      effects of female sexual dysfunction (FSD) have been improved increasingly. This
      review summarizes the basic therapeutic approaches to FSD, including
      psychotherapy, sexual behavior therapy, mechanical skills, life style adjustment,
      physical exercise, acupuncture, medication, surgery, and gene therapy. It also
      points out the objective understanding of the limitations of the available
      therapeutic methods, with stress on patient-oriented comprehensive therapeutic
      principles and increased attention to recognition education among the patients so
      as to improve the present status of FSD treatment.

PMID- 24738454
TI  - [Microwave radiation induces injury to GC-2spd cells].
AB  - OBJECTIVE: To explore the impact of microwave radiation on GC-2spd cells.
      METHODS: We exposed cultured GC-2spd cells to microwave radiation at the average
      power densities of 0, 10 and 30 mW/cm2 for 15 minutes and, from I to 24 hours
      after the exposure, we observed the changes in cell proliferation, histology and
      ultrastructure, cell apoptosis, and cAMP content by MTIT, light microscopy,
      electron microscopy, flow cytometry and ELISA. RESULTS: Compared with the control
      group, the GC-2spd cells showed a significant decrease in proliferation ability
      at 1 -24 hours after 10 and 30 mW/cm2 microwave radiation, except at 12 hours
      after 30 mW/cm2 radiation (P <0.05 or P <0.01), with reduced length and number of
      cell enation and increased intra cytoplasm vacuoles. The rate of cell apoptosis
      (%) was significantly increased in the 10 and 30 mW/cm2 groups at 6 hours (4.56
      +/- 2.09 vs 14.59 +/- 1.09 and 8.48 +/- 1.73, P <0.05 or P <0.01) , with
      agglutination and margin translocation of chromatins and obvious dilation of endo
      cytoplasmic reticula. The cAMP content (nmol/g) in the GC-2spd cells was
      remarkably reduced in the 10 and 30 mW/cm2 groups at 6 and 24 hours (2.77 +/-0.24
      vs 1.65+/- 0. 17 and 1.96+/-0.10, 3.02 +/-0.47 vs 2.13 +/-0.33 and 1.69 +/-0.27,
      P <0.05 or P <0.01). CONCLUSION: Microwave radiation at 10 and 30 mW/cm2 may
      cause injury to GC-2spd cells, which is manifested by decreased content of
      intracellular cAMP, reduced activity of cell proliferation, and increased rate of
      cell apoptosis.

PMID- 24738455
TI  - [Effects of adenovirus-mediated PTEN on the proliferation of prostate cancer PC-3
      cells and expressions of cyclin D1 and p21].
AB  - OBJECTIVE: To construct a recombinant adenovirus expression vector containing the
      anti-oncogene PTEN and to investigate the effects of the PTEN gene on the
      proliferation of prostate cancer PC-3 cells and the expressions of cyclin D1 and
      p21 in the PC-3 cells. METHODS: The PTEN gene was amplified from the rat
      hippocampus by RT-PCR and cloned into the shuttle plasmid pEN-TR2A. The plasmids
      were constructed and amplified in 293A cells. Prostate cancer PC-3 cells were
      cultured in vitro and infected with the adenoviral vector carrying the PTEN gene
      (Ad-PTEN). The up-regulation of the PTEN protein was measured by indirect immuno
      fluorescence assay; the expressions of PTEN, cyclin D1 and p21 in the cells
      infected with Ad-PTEN and Ad-LacZ were determined by RESULTS: The Western blot;
      and the effect of PTEN on the cell proliferation was detected by MTT assay and
      plate colony formation. recombinant adenoviral vector Ad-PTEN was successfully
      constructed. Western blot showed a significantly increased expression of the PTEN
      protein in the PC-3 cells infected with Ad-PTIEN (0.215 +/-0.065) as compared
      with that in the control ([0.052 +/-0.009], t = 4. 30, P <0.05) and the Ad-LacZ
      group ( [0. 056 +/- 0.008 ] , t =4.21, P <0.05). The expression of cyclin D1 was
      significantly lower in the Ad-PTEN-infected PC-3 cells (0. 256 +/- 0. 072) than
      in the control ( [0. 502 +/- 0. 087 ], t = 3.77, P < 0.05) and the Ad-LacZ group
      ([0.498 +/-0.081] , t =3.87, P <0.05), while the expression of p21 remarkably
      higher in the Ad-PTEN-infected PC-3 cells (0.589 +/-0. 076) than in the control
      ([0. 146 +/-0.026] , t = 9.55, P<0. 01) and the Ad-LacZ group ([0. 163 +/-0. 024]
      , t = 9.26, P <0.01). Ad-PTEN significantly inhibited the growth of the PC-3
      cells (21.98%) at 48 h (t = 6.80, P <0.01). The colony formation rate of the PC-3
      cells was (37.4 +/-4. 18)% in the Ad-PTEN group, significantly lower than (54.9
      +/-4.81)% in the control (t =4.76, P<0.01) and (56.5 +/- 5.42)% in the Ad-LacZ
      group (t=4.83, P<0.01). CONCLUSION: The expression of PTEN induced by Ad-PTEN can
      significantly inhibit the proliferation of PC-3 cells, down-regulate the
      expression of cyclin D1, and up-regulate the expression of p21.

PMID- 24738456
TI  - [Effects of cyclopamine on the proliferation and apoptosis of LNCaP cells and
      expression of the PCA3 gene in human prostate cancer].
AB  - OBJECTIVE: To explore the effects of cyclopamine on the proliferation and
      apoptosis of LNCaP cells and the expression of the PCA3 gene in human prostate
      cancer in vitro. METHODS: LNCaP cells were treated with cyclopamine at the
      concentrations of 1, 5, 10 and 15 micromol/L for 24, 48 and 72 hours. The
      inhibitory effects of cyclopamine on the proliferation and apoptosis of the LNCaP
      cells were detected by MTT and flow cytometry respectively, the morphological
      changes of the cells observed by Hoechst 33258 staining, and the expression of
      the PCA3 gene determined by real-time fluorescence quantitative reverse
      transcriptase polymerase chain reaction (FQ-RT-PCR). RESULTS: Compared with the
      blank control group, cyclopamine significantly inhibited the proliferation of the
      LNCaP cells at 5, 10 and 15 micromol/L (P <0.01), reaching IC50 at 10 micro mol/L
      at 48 hours. The apoptosis rates of the LNCaP cells at 24, 48 and 72 hours were
      37.21%, 57.38% and 57.98% in the 10 micromol/L group and 21. 16% , 71.31% and
      72.90% in the 15 micro.mol/L group, significantly different from those in the
      control (P <0. 01). The cell apoptosis showed a rising trend with the increase of
      cyclopamine concentration and acting-time, while the expression of the PCA3 gene
      was decreasing with the increased concentration of cyclopamine, significantly
      lower than that of the blank control group (P <0.01) , and extremely low in the
      10 micromo/L group CONCLUSION: Cyclopamine intervention at 10 and 15 micromol/L
      for 48 and 72 hours could significantly inhibit the at all time points.
      Proliferation and induce the apoptosis of LNCaP cells and reduce the expression
      level of PCA3.

PMID- 24738457
TI  - [Bortezomib enhances the sensitivity of prostate cancer cells to natural killer
      cell-mediated cytotoxicity].
AB  - OBJECTIVE: To investigate whether bortezomib can enhance the sensitivity of human
      prostate cancer (PCa) cells to natural killer (NK) cell-mediated cytotoxicity,
      and whether it produces the same effect on different PCa cell lines. METHODS: We
      treated androgen-dependent PCa LNCaP cells and androgen-independent PCa DU145
      cells with bortezomib at the concentrations of 0, 5, 10, 15, 20 and 25 nmol/L for
      24, 48 and 72 hours, and then detected the proliferation and apoptosis of the
      tumor cells by CCK-8 and Annexin V/PI, respectively. RESULTS: The proliferation
      rates of the DU145 cells treated with 15, 20 and 25 nmol/L bortezomib were (82.79
      +/-2.04)%, (73.59+/- 2.95)% and (74.16+/- 6. 16)% at 48 hours and (71.24+/-
      5.30)%, (51.20+/- 2.91)% and (38.02+/- 2.67)% at 72 hours, and those of the LNCaP
      cells were (77.04+/- 7.74)% , (42.61 +/- 6.62)% and (23.85 +/-6.04)% at 48 hours
      and (36.45 +/-7.02)%, (14.94 +/-5.76)% and (11.65 +/-5. 87)% at 72 hours, both
      significantly inhibited as compared with the control group (P <0.05). At 24
      hours, the apoptosis rates of the DU145 cells treated with 15, 20 and 25 nmol/L
      bortezomib were (14.41 +/- 1.32)% , (16.13 +/- 1.55)% and (14.48 +/- 1.42)% , and
      those of the LNCaP cells treated with 20 and 25 nmol/L bortezomib were (12.77 +/-
      1.28)% and (14. 84 +/- 1.65)% , significantly higher than those of the control
      group (P <0.05) , and the DU145 cells showed an even higher sensitivity to
      bortezomib than the LNCaP cells. Bortezomib failed to sensitize these two cell
      lines to NK cell-mediated cytotoxicity in short-term assay, while long-term assay
      manifested that the apoptosis rates of DU145 and LNCaP cells after treated with
      20 nmol/L bortezomib + NK cells were (41.83 +/- 5.06)% and (30.31 +/- 3.62)% ,
      respectively, significantly higher CONCLUSION: Bortezomib enhances the
      sensitivity of than those after treated with either bortezomib or NK cells alone
      (P <0.05). PCa cells to NK cell-mediated cytotoxicity and adds to the effect of
      current cancer therapies, and it is more efficacious for androgen-independent
      prostate cancer.

PMID- 24738458
TI  - [Inhibition of stromal interaction molecule 1 and the expression of apoptosis
      related proteins in prostate cancer PC-3 cells].
AB  - OBJECTIVE: To explore the effects of stromal interaction molecule 1 (STIM1) on
      the expression of apoptosis-related proteins in prostate cancer PC-3 cells.
      METHODS: We transfected the lentivirus vector STIM1-pGCSIL-GFP carrying STIM
      shRNA into human hormone-independent prostate cancer PC-3 cells, and 3 days later
      observed the transfection efficiency by fluorescence microscopy. At 7 days after
      transfection, we determined the expression of STIM1 in the PC-3 cells by RT-PCR
      and Western blot and those of apoptosis-related proteins Bcl-2, Bax, survivin and
      activated Caspase-3 by Western blot. RESULTS: At 3 days, inverted microscopy
      revealed a transfection efficiency of > 80%. At 7 days, the STIM1 expression was
      significantly inhibited at both mRNA and protein levels. The Bcl-2/Bax rate was
      remarkably decreased as compared with that of the control group (0. 31 vs 1.24 )
      , and the survivin expression was markedly reduced, 0. 14 times that of the
      relative expression in the control. However, the Caspase-3 cleavage was
      significantly activated, 1.52 times that of the control (P <0.05). CONCLUSION:
      STIM1 can be regarded as an oncogene in prostate cancer PC-3 cells. Inhibition of
      its expression can induce PC-3 cell apoptosis by reducing the Bcl-2/Bax rate,
      decreasing the survivin expression, and activating the Caspase-3 pathway.

PMID- 24738459
TI  - [Prognostic value of PSA kinetics in locally advanced prostate cancer treated by
      maximal androgen blockade combined with brachytherapy].
AB  - OBJECTIVE: To evaluate the effect of post-treatment PSA kinetics on the prognosis
      of prostate cancer (PCa). METHODS: We retrospectively reviewed the clinical data
      of 114 cases of locally advanced PCa treated by maximal androgen blockade (MAB)
      combined with brachytherapy, and analyzed the association of the changes in PSA
      kinetics with the prognosis of the patients. RESULTS: The median survival time of
      the patients was 81 (15 - 144) months, with 1-, 3- and 5-year survival rates of
      91. 23%, 78.07% and 68.42% , respectively. Univariate analysis indicated that the
      baseline PSA level, PSA nadir, the time of PSA decreasing to nadir, PSA doubling
      time, and the extent of PSA declining were all predictive factors for the
      survival time of the PCa patients. Multivariate analysis demonstrated that PSA
      nadir, the time of PSA decreasing to nadir, and the extent of PSA declining were
      three independent prognostic factors, which prolonged the long-term survival of
      the patients by 1.7, 3.2 and 6.8 times, respectively. CONCLUSION: For locally
      advanced PCa treated by MAB combined with brachytherapy, PSA nadir <1 micro g/L,
      the time to nadir <3 months, and the extent of PSA declining >96% are independent
      prognostic factors.

PMID- 24738460
TI  - [Diagnosis of prostate cancer with PSA < or =4.0 microg/L].
AB  - OBJECTIVE: To evaluate digital rectal examination (DRE) , transrectal
      ultrasonography (TRUS) , free/total (f-PSA/ t-PSA) prostate-specific antigen
      (PSA), and PSA density (PSAD) in the diagnosis of prostate cancer (PCa) in
      patients with PSA < or = 4.0 microg/L. METHODS: Between April 1996 and December
      2012, a total of 343 subjects, aged 30 -91 years, with PSA < or =4.0 microg/L and
      abnormal findings on DRE or TRUS underwent prostatic biopsy. Based on the levels
      of PSA, the subjects were divided into four groups: 0 -1.0, 1.1 -2. 0, 2.1 -3. 0,
      and 3.1 -4.0 microg/L. The diagnostic values of DRE, TRUS, f-PSA/t-PSA, and PSAD
      were assessed in those with different PSA levels. According to the age, the
      subjects were again divided into five groups: C49 yr, 50 -59 yr, 60 -69 yr, 70 
      79 yr, and > 80 yr. The rates of PCa detection in relation to PSA levels were
      estimated in different age groups. RESULTS: Of the 343 subjects, 65 (19.0% ) were
      diagnosed with PCa, with detection rates of 16.28% (21/129) , 17. 17% (17/99),
      21.82% (12/55), and 25.00% (15/60) in those with the PSA levels of 0 -1.0, 1.1 
      2.0, 2.1 -3.0, and 3.1 -4.0 microg/L, respectively. There were statistically
      significant differences in f-PSA/t-PSA between the PCa patients and non-PCa
      subjects with the PSA level > 2.0 microg/L (P <0.05) , but not with the PSA level
      < or =2.0 microg/L (P > 0.05) , nor did PSAD show any significant difference
      between the PCa and non-PCa groups ([0.09+/-0. 16] versus [0. 06 +/- 0. 07]
      micro/L/ml, P > 0. 05). The rate of cancer detection rose -with the elevation of
      the PSA level, but had no statistically significant difference among different
      age groups (P >0.05). CONCLUSION: PSA 2.1 -4.0 microg/L with abnormal DRE and
      TRUS findings should be considered as a warning signal, which requires regular
      follow-up and PSA detection. With f-PSA/t-PSA <0. 15 with or without abnormal DRE
      and TRUS findings, routine prostate biopsy should be performed. PCa diagnosis
      cannot be effectively established by DRE, TRUS, f-PSA/t-PSA, and PSAD in those
      with PSA < or = 2.0 microg/L.

PMID- 24738461
TI  - [Efficacy of combination therapy of tamsulosin and solifenacin for mild and
      moderate benign prostatic hyperplasia with overactive bladder].
AB  - OBJECTIVE: To evaluate the efficacy and safety of the combination therapy of
      tamsulosin and solifenacin for mild and moderate benign prostatic hyperplasia
      (BPH) with overactive bladder (OAB). METHODS: We randomly divided 166 patients
      with BPH and concomitant OAB into a mild obstruction symptom group (n = 88) and a
      moderate obstruction symptom group (n =78), 48 of the former group treated with
      0. 2 mg tamsulosin + 5 mg solifenacin and the other 40 with 0. 2 mg tamsulosin;
      36 of the latter group treated with 0. 2 mg tamsulosin + 5 mg solifenacin and the
      other 42 with 0. 2 mg tamsulosin, all administered once daily for 12 weeks. We
      obtained the International Prostate Symptom Score (IPSS), urine storage period
      symptom score (USPSS), voiding symptom score (VSS), Qmax, residual urine volume,
      OAB symptom score (OABSS) and adverse reactions, and compared them among
      different RESULTS: Among the patients with mild obstruction symptoms, the
      combination of tamsulosin and solifenacin achieved remark-groups. able
      improvement in IPSS, USPSS, Qmax and OABSS as compared with the baseline (P <
      0.05), but made no significant difference in the residual urine volume (P > 0.
      05) , while tamsulosin improved IPSS only (P < 0.05). The combination therapy
      exhibited an obvious superiority over tamsulosin alone in improving IPSS (9.7
      micro 3.0 vs 15.8 micro 3.3), USPSS (8. 1 micro 1.7 vs 12.3 micro 3.1), Qmax
      ([18.6 micro 2.3] ml/s vs [14.2 micro 2.3] ml/s ), and OABSS (5.3micro 1.3 vs 9.7
      micro 2.7) (P < 0.05), but there were no obvious differences in residual urine,
      urine routine test results and adverse events between the two therapies ( P > 0.
      05). In those with moderate obstruction symptoms, the combination therapy
      significantly improved IPSS, VSS, Qmax and OABSS (P < 0.05) but not the residual
      urine (P > 0. 05) in comparison with the baseline. The tamsulosin therapy
      achieved obvious improvement in IPSS, VSS, Qmax, OABSS and residual urine. The
      combination therapy showed a better effect than tamsulosin only in OABSS (4. 8 +/
      1.5 vs 6.5 +/-2.5, P < 0.05), but no significant differences from the latter in
      IPSS, Qmax, VSS, routine urine test results, and adverse CONCLUSION: Combination
      therapy of tamsulosin and solifenacin is obviously safe and efficacious in the
      treatment (P > 0.05). events of both mild and moderate BPH with concomitant OAB,
      and it is superior to tamsulosin alone.

PMID- 24738462
TI  - [Urinary prostaglandins E2 correlates to overactive bladder symptoms in patients
      with benign prostatic hyperplasia].
AB  - OBJECTIVE: To measure the levels of urinary prostaglandins E2 (PGE2) in benign
      prostatic hyperplasia (BPH) patients with or without overactive bladder (OAB)
      symptoms and determine whether urinary PGE2 can serve as a biomarker for BPH
      related OAB. METHODS: This study included 86 BPH patients and 34 male control
      subjects without lower urinary tract symptoms. Based on the OAB symptom scores
      (OABSS), the BPH cases were classified as BPH/OAB (n =49) and BPH/non-OAB (n =
      37) to be treated orally with tamsulosin alone and tamsulosin + tolterodine
      tartrate, respectively, for 12 weeks. We measured the urinary PGE2 levels of all
      the subjects by ELISA before and after medication, the total PGE2 level
      normalized to the concentration of the urinary creatinine (PGE2/Cr). We also
      obtained the residual urine volume, Qmax, prostate volume, PSA level, IPSS and
      OABSS of the BPH patients, and compared them among different groups. RESULTS: The
      baseline PGE2/Cr level was significantly lower in the control than in the BPH/OAB
      and BPH/non-OAB groups (both P <0.05), and higher in the BPH/OAB than in the
      BPH/non-OAB patients (P <0.05). After 12 weeks'treatment, the urinary PGE2/Cr
      level was remarkably decreased with relief of the OAB symptoms in the BPH/OAB
      patients (P <0.05) , but not in the BPH/non-OAB group (P >0.05). The
      concentration of PGE2 was not correlated with the IPSS storage score and OABSS of
      the BPH/OAB patients (P >0.05). CONCLUSION: Patients with BPH/OAB have
      significantly higher urinary PGE2/Cr levels than those with BPH/non-OAB and
      normal controls, which tend to decrease with the alleviation of OAB symptoms. Our
      findings suggest that urinary PGE2 can be a potential biomarker for BPH/OAB.

PMID- 24738463
TI  - [Early removal of the urethral catheter after transurethral plasma kinetic
      resection of the prostate in the treatment of BPH].
AB  - OBJECTIVE: To investigate the feasibility and effect of early removal of the
      urethral catheter after transurethral plasma kinetic resection of the prostate
      (PKRP) in the treatment of benign prostatic hyperplasia (BPH). METHODS: We
      equally randomized 128 BPH patients treated by PKRP to an experimental group and
      a control group, urethral catheters removed at 1 -2 days for the former and at 5 
      7 days for the latter. We compared the relevant indexes and clinical effects
      between the two groups. RESULTS: The baseline data were not significantly
      different between the two groups. Compared with the controls, the experimental
      group showed a significantly shorter postoperative hospital stay ([6.8 +/- 1.9] d
      vs [3.7 +/- 1.5] d, P < 0.05) and lower infection rate (25.0% vs 10.9%, P <
      0.05). All the patients were followed up for 3 -6 months postoperatively. At 3
      months after surgery, both the experimental and the control groups showed
      remarkable improvement in the International Prostatic Symptoms Scores (4. 9 +/-
      2. 2 vs 5. 3 +/- 2. 3), maximum urine flow rate ([21.5+/- 5.6 ] ml/s vs [19.1 +/
      4.9 ] ml/s) , and residual urine ( [ 16.8+/- 10.3 ] ml vs [18.9 +/- 12.3 ] ml),
      but with no significant differences between the two (P > 0.05) , and no
      significant differences were observed in postoperative complications (P >0.05).
      CONCLUSION: Early removal of the urethral catheter after PKRP, with its
      advantages of shorter postoperative hospital stay, lower infection rate, and no
      influence on the long-term effect, deserves to be recommended as a routine method
      in the treatment of BPH.

PMID- 24738464
TI  - [Influence of the reference values for semen analysis proposed in the 5th edition
      of WHO laboratory manual on the indication spectrum for intrauterine
      insemination].
AB  - OBJECTIVE: To study the influence of the reference values for semen analysis
      proposed in the 5th edition of the WHO Laboratory Manual for the Examination and
      Processing of Human Semen on the indication spectrum for intrauterine
      insemination (IUI). METHODS: We retrospectively analyzed the clinical data of 111
      cycles of IUI by the reference values for semen analysis in the 4th edition of
      the WHO Laboratory Manual (group A) and 84 cycles by the 5th edition (group B).
      We recorded and compared the percentages of various indications for IUI between
      the two groups. RESULTS: The complications for IUI in groups A and B were as
      follows: asthenospermia (87.4% [97/111] vs 55.9% [47/84], P < 0.05), oligospermia
      (0 vs 0), teratospermia (51.4% [57/111] vs 35.7% [30/84]) , abnormal liquefaction
      (0.9% [1/111] vs O) , sexual dysfunction and genital malformation (0 vs 3.6%
      [3/84] , immune infertility (0.9% [ 1/111] vs O), and unexplained infertility
      (3.6% [4/111] vs 2. 4% [2/84 ] ). There were no significant differences between
      the two groups in the percentages of all the indications except that of
      asthenospermia. CONCLUSION: The reference values for semen analysis proposed in
      the 5th edition of the WHO Laboratory Manual for the Examination and Processing
      of Human Semen have an evident influence on the indication spectrum for IUI by
      largely reducing the cases of IUI for male factors, prolonging the cycles of some
      patients, causing excessive diagnosis and treatment for females, and increasing
      their mental and economic burdens.

PMID- 24738465
TI  - [Correlation of sex hormones and parathyroid hormone with biochemical markers of
      bone turnover in aged men].
AB  - OBJECTIVE: To investigate the correlation of serum sex hormones and parathyroid
      hormone (PTH) with the biochemical markers of bone turnover in aged men. METHODS:
      We collected the laboratory data of 465 men aged 60- 93 (73. 1 +/- 8. 3) years
      old, who came for routine physical examinations in our hospital. We obtained the
      levels of serum follicle- stimulating hormone (FSH), luteinizing hormone (LH),
      estradiol (E2), testosterone (T), sex hormone binding globulin (SHBG), PTH, 25
      hydroxy-vitamin D3 (25(OH) D3), and bone turnover markers C-terminal telopeptide
      of type I collagen (CTX), osteocalcin (OC) and amino-terminal propeptide of type
      I procollagen (PINP). We also determined free testosterone (FT) , bioactive
      testosterone (BT) , testosterone secretion index (TSI) and FT index (FTI), and
      analyzed the correlation of each index with the biochemical markers of bone
      turnover. RESULTS: The concentrations of serum FSH, LH, and SHBG increased, while
      the levels of FT, BT, TSI, FTI, PTH, CTX, OC and PINP decreased with age,
      especially in those over 80 years old (P <0.05). PTH was positively correlated
      with CTX, OC and PINP (r =0. 227, 0. 269 and 0. 162, P <0. 01), even after the
      adjustment for age, while SHBG negatively correlated with OC (r = -0. 100, P
      <0.05). The bone turnover markers increased with the elevation of the PTH
      quartiles, with significant differences between the first and the fourth quartile
      (P <0. 01). Multiple stepwise regression analysis showed that age was correlated
      inversely with CTX, OC and PINP ( beta = -0. 126, -0. 141 and -0. 122, P <0.05) ,
      PTH positively with the three markers (beta = 0. 196, 0.279 and 0.189; P <0.
      001), and SHBG negatively with OC ( beta = -0. 100, P <0.05) . CONCLUSION: Aging
      is the fundamental cause of reduced bone turnover in aged men. The levels serum
      PTH and SHBG are significantly associated with the biochemical markers of bone
      turnover.

PMID- 24738466
TI  - [Comprehensive treatment of stage-lllb testicular non-seminomatous germ cell
      tumor: a case report and review of the literature].
AB  - OBJECTIVE: To investigate the comprehensive treatment of stage-IIIb testicular
      non-seminomatous germ cell tumor (NSGCT) based on the chemotherapy with
      cisplatin, etoposide and bleomycin (BEP) and nerve-sparing laparoscopic
      retroperitoneal lymph node dissection (nsLRPLND). METHODS: We reported a case of
      stage-IIIb testicular NSGCT, analyzed the clinical data and treatment methods and
      reviewed the relevant literature. RESULTS: The patient underwent chemotherapy
      with etoposide (0. 18 g/d for the first 3 days), cisplatin (30 mg/d for the first
      5 days), and bleomycin (30 mg/d on day 2, 9 and 16) for 3 cycles, followed by
      nsLRPLND. Both chemotherapy and surgery were successfully performed. The
      operation time was 175 min, with intraoperative blood loss of 50 ml, but no
      severe perioperative complications. No recurrence and distant metastasis were
      found during the 6-month follow-up after surgery. CONCLUSION: The comprehensive
      treatment based on BEP chemotherapy and nsRPLND can be used as an option for
      stage-IIIb testicular NSGCT.

PMID- 24738467
TI  - [Low-dose tadalafil combined with Shuganyiyang capsules for mild-to-moderate
      erectile dysfunction].
AB  - OBJECTIVE: To observe the clinical effect of low-dose once-daily tadalafil
      combined with Shuganyiyang Capsules in the treatment of mild-to-moderate erectile
      dysfunction (ED). METHODS: Ninety patients with mild-to-moderate ED were equally
      randomized to groups A, B and C to receive Shuganyiyang Capsules, tadalafil, and
      tadalafil + Shuganyiyang Capsules, respectively. The scores of the patients on
      IIEF-5 and SF-PAIRS (15-Item Short Form of Psychological Interpersonal
      Relationship Scales) were recorded before and at 1 and 3 months after treatment.
      RESULTS: The IIEF-5 scores of groups A, B and C were 10.13 +/- 1.55, 11.00 + 1.60
      and 10.73 +/- 1.91 before treatment, and 13.77 +/- 2.11, 17.77 +/- 2.13 and 17.17
      +/- 3.84 at 1 month after treatment, significantly higher in B and C than in A (P
      <0. 001) , but with no remarkable difference between B and C (P =0. 411). At 3
      months after treatment, the IIEF-5 scores were 15.77 +/- 2.05, 18.07 +/- 2.24 and
      19.37 +/- 3.76 in the three groups, dramatically higher in B and C than in A (P
      <0.001) as well as in C than in B (P<0.05). The scores on sexual self-confidence,
      sexual spontaneity and time concerns in SF-PAIRS were 3.90 +/-0.80, 8.67 +/- 1.94
      and 14.43 +/- 1.92 before medication, 5.83 +/- 1.02, 9.90 +/- 1.75 and 11.17 +/-
      1.68 at 1 month and 6.73 +/- 0.98, 11.07 +/- 2.08 and 10.67 +/-1.60 at 3 months
      after medication in group A; 4.17 +/- 0.87, 9.37 +/-1.43 and 14.47 +/-1.57 before
      medication, 6.47 +/-0.78, 10.83 +/- 2.18 and 10.20 +/-1.56 at 1 month and 6.83 +/
      0.91, 11.30 +/- 1.88 and 9.47 +/- 1.57 at 3 months in group B; and 4.23 +/-0. 94,
      9.50 +/- 1.89 and 14.67 +/- 2.91 before medication, 8.03 +/- 1.67, 13.43 +/-1.10
      and 9.70 +/-1.21 at 1 month and 8.93 +/- 1.78, 14.70 +/- 1.26 and 8. 87 +/- 0. 97
      at 3 months in group C. Compared with the baseline, the SF-PAIRS scores of the
      three groups were all significantly improved after treatment (P <0. 05) , and
      markedly higher in C than in the other two groups (P <0.05). CONCLUSION: Low-dose
      once-daily tadalafil combined with Shuganyiyang Capsules is obviously effective
      in the treatment of mild-to-moderate ED, which not only improves the
      patients'erectile function, sexual self-confidence and sexual spontaneity, but
      also reduces their time concerns.

PMID- 24738468
TI  - [Generation and regulation of Leydig cells].
AB  - Leydig cells, located in the loose interstitial tissue of seminiferous tubules,
      are the major site for androgen synthesis and secretion, and play an important
      role in the reproductively and fertility of males. The dysfunction of Leydig
      cells may lead to various male diseases, such as primary hypogonadism,
      cryptorchidism, and hypospadias. This review outlines the recent findings
      concerning the generation, development and regulation of Leydig cells.

PMID- 24738469
TI  - [Autophagy and prostate cancer].
AB  - The role of autophagy is known to be highly complex and context-dependent, and
      may be characterized as both tumor suppression and tumor promotion in some
      tumors, such as breast cancer and prostate cancer. This review outlines recent
      advances in the studies of the involvement of autophagy in the development,
      progression and treatment of prostate cancer, focusing on autophagy modulation
      during androgen deprivation, with a special discussion on the regulatory effect
      of androgens on the autophagy of prostate cancer cells. A critical evaluation and
      analysis of the studies suggests that autophagy inhibition combined with androgen
      deprivation therapy is a promising approach to the treatment of prostate cancer.

PMID- 24738470
TI  - Unexpected NO transfer reaction between trans-[Ru(II)(NO+)(NH3)4(L)]3+ and
      Fe(III) species: observation of a heterobimetallic NO-bridged intermediate.
AB  - The reaction between trans-[Ru(II)(NO(+))(NH3)4(L)](3+), L = ImN, IsN, Nic,
      P(OMe)3, P(OEt)3, and P(OH)(OEt)2, and the Fe(III) species [Fe(III)(TPPS)],
      metmyoglobin, and hemoglobin was monitored by UV-vis, EPR, and electrochemical
      techniques (DPV, CV). No reaction was observed when L = ImN, IsN, Nic, and
      P(OH)(OEt)2. However, when L = P(OMe)3 and P(OEt)3, the reaction was quantitative
      and the products were trans-[Ru(III)(H2O)(NH3)4(P(OR)3)](3+) and [Fe(II)(NO(+))]
      species. Reaction kinetics data and DFT calculations suggest a two-step reaction
      mechanism with the initial formation of a bridged [Ru-(MUNO)-Fe] intermediate,
      which was confirmed through electrochemical techniques (E(0)' = -0.47 V vs NHE).
      The calculated specific rate constant values for the reaction were in the ranges
      k1 = 1.1 to 7.7 L mol(-1) s(-1) and k2 = 2.4 * 10(-3) to 11.4 * 10(-3) s(-1) for
      L = P(OMe)3 and P(OEt)3. The oxidation of the ruthenium center (Ru(II) to
      Ru(III)) containing the nitrosonium ligand suggests that NO can act as an
      electron transfer bridge between the two metal centers. 

PMID- 24738471
TI  - Multispecies QSAR modeling for predicting the aquatic toxicity of diverse organic
      chemicals for regulatory toxicology.
AB  - The research aims to develop multispecies quantitative structure-activity
      relationships (QSARs) modeling tools capable of predicting the acute toxicity of
      diverse chemicals in various Organization for Economic Co-operation and
      Development (OECD) recommended test species of different trophic levels for
      regulatory toxicology. Accordingly, the ensemble learning (EL) approach based
      classification and regression QSAR models, such as decision treeboost (DTB) and
      decision tree forest (DTF) implementing stochastic gradient boosting and bagging
      algorithms were developed using the algae (P. subcapitata) experimental toxicity
      data for chemicals. The EL-QSAR models were successfully applied to predict
      toxicities of wide groups of chemicals in other test species including algae (S.
      obliguue), daphnia, fish, and bacteria. Structural diversity of the selected
      chemicals and those of the end-point toxicity data of five different test species
      were tested using the Tanimoto similarity index and Kruskal-Wallis (K-W)
      statistics. Predictive and generalization abilities of the constructed QSAR
      models were compared using statistical parameters. The developed QSAR models (DTB
      and DTF) yielded a considerably high classification accuracy in complete data of
      model building (algae) species (97.82%, 99.01%) and ranged between 92.50%-94.26%
      and 92.14%-94.12% in four test species, respectively, whereas regression QSAR
      models (DTB and DTF) rendered high correlation (R(2)) between the measured and
      model predicted toxicity end-point values and low mean-squared error in model
      building (algae) species (0.918, 0.15; 0.905, 0.21) and ranged between 0.575 and
      0.672, 0.18-0.51 and 0.605-0.689 and 0.20-0.45 in four different test species.
      The developed QSAR models exhibited good predictive and generalization abilities
      in different test species of varied trophic levels and can be used for predicting
      the toxicities of new chemicals for screening and prioritization of chemicals for
      regulation. 

PMID- 24738472
TI  - QM/MM-MD simulations of conjugated polyelectrolytes: a study of luminescent
      conjugated oligothiophenes for use as biophysical probes.
AB  - A methodological development is reported for the study of luminescence properties
      of conjugated polyelectrolytes, encompassing systems in which dihedral rotational
      barriers are easily overcome at room temperature. The components of the model
      include (i) a molecular mechanics (MM) force field description of the solvent in
      its electronic ground state as well as the chromophore in its electronic ground
      and excited states, (ii) a conformational sampling by means of classical
      molecular dynamics (MD) in the respective electronic states, and (iii) spectral
      response calculations by means of the quantum mechanics/molecular mechanics QM/MM
      approach. A detailed analysis of the combined polarization effects of the ionic
      moiety and the polar water solvent is presented. At an increased computational
      cost of 30% compared to a calculation excluding the solvent, the error in the
      transition wavelength of the dominant absorption band is kept as small as 1 nm as
      compared to the high-quality benchmark result, based largely on a QM description
      of the solvent. At a reduced computational cost the error of the same quantity is
      kept as small as 6 nm, with the cost reduction being the result of an effective
      description of the effects of the solvent by means of replacing the carboxylate
      ions with neutral hydrogens. In absorption spectroscopy, the obtained best
      theoretical results are in excellent agreement with the experimental benchmark
      measurement, regarding excitation energies as well as band intensities and
      profiles. In fluorescence spectroscopy, the experimental spectrum shows a
      vibrational progression that is not addressed by theory, but the theoretical band
      position is in excellent agreement with experiment, with a highly accurate
      description of the Stokes shift as a result. 

PMID- 24738476
TI  - New melatonin-N,N-dibenzyl(N-methyl)amine hybrids: potent neurogenic agents with
      antioxidant, cholinergic, and neuroprotective properties as innovative drugs for
      Alzheimer's disease.
AB  - Here, we describe a new family of melatonin-N,N-dibenzyl(N-methyl)amine hybrids
      that show a balanced multifunctional profile covering neurogenic, antioxidant,
      cholinergic, and neuroprotective properties at low-micromolar concentrations.
      They promote maturation of neural stem cells into a neuronal phenotype and thus
      they could contribute to CNS repair. They also protect neural cells against
      mitochondrial oxidative stress, show antioxidant properties, and inhibit human
      acetylcholinesterase (AChE). Moreover, they displace propidium from the
      peripheral anionic site of AChE, preventing the beta-amyloid aggregation promoted
      by AChE. In addition, they show low cell toxicity and can penetrate into the CNS.
      This multifunctional profile highlights these melatonin-N,N-dibenzyl(N
      methyl)amine hybrids as useful prototypes in the research of innovative drugs for
      Alzheimer's disease. 

PMID- 24738473
TI  - Silicon-containing GABA derivatives, silagaba compounds, as orally effective
      agents for treating neuropathic pain without central-nervous-system-related side
      effects.
AB  - Neuropathic pain is a chronic condition resulting from neuronal damage.
      Pregabalin, the (S)-isomer of 3-isobutyl-gamma-aminobutyric acid (GABA), is
      widely used to treat neuropathic pain, despite the occurrence of central nervous
      system (CNS)-related side effects such as dizziness and somnolence. Here we
      describe the pharmacology of novel GABA derivatives containing silicon-carbon
      bonds, silagaba compounds. Silagaba131, 132, and 161 showed pregabalin-like
      analgesic activities in animal models of neuropathic pain, but in contrast to
      pregabalin they did not impair neuromuscular coordination in rotarod tests.
      Pharmacokinetic studies showed that brain exposure to silagaba compounds was
      lower than that to pregabalin. Surprisingly, despite their potent analgesic
      action in vivo, silagaba compounds showed only weak binding to alpha2-delta
      protein. These compounds may be useful to study mechanisms of neuropathic pain.
      Our results also indicate that silagaba132 and 161 are candidates for orally
      effective treatment of neuropathic pain without CNS-related side effects. 

PMID- 24738477
TI  - Gianotti-Crosti syndrome in a postpartum adult.

PMID- 24738478
TI  - On the remarkable role of surface topography of the bottom electrodes in blocking
      leakage currents in molecular diodes.
AB  - It was proposed in 1974 that molecules could rectify, but molecular diodes with
      simultaneously high rectification ratios, yields of working junctions, and
      reproducibility are rare, despite a huge body of experimental work. Although
      every type of molecular junction contains a certain distribution of defects
      induced by the topography of the surface, the roles of these defects in the
      device performance are rarely studied. We show that control over the topography
      of the bottom electrode in self-assembled monolayer (SAM)-based junctions in
      terms of the number of grains, the width of the grain boundaries, and the
      roughness improves the yield of working junctions from 60% to near 100%,
      increases reproducibility by a factor of 3, and boosts the rectification ratio of
      a molecular diode (from nearly unity to ~1.0 * 10(2)) by minimizing the leakage
      currents. We found that commonly used metal surfaces fabricated by direct
      deposition methods are inferior to template-stripped surfaces, which are flat and
      contain only small areas of exposed grain boundaries, at which SAMs cannot pack
      well. Thus, for molecular diodes to perform well, it is crucial to minimize
      leakage currents by limiting the amount of exposed grain boundaries.

PMID- 24738479
TI  - alpha-Lipoic acid prolongs survival and attenuates acute kidney injury in a rat
      model of sepsis.
AB  - Acute kidney injury is a frequent and serious complication in patients with
      severe sepsis. alpha-Lipoic acid (ALA), a naturally occurring dithiol compound,
      has been shown to possess anti-inflammatory and anti-oxidative properties. In the
      present study we investigated whether ALA could attenuate acute kidney injury and
      improve survival in a rat model of sepsis. Rats were subjected to caecal ligation
      and puncture (CLP) to induce sepsis. alpha-Lipoic acid (200 mg/kg) was
      administered by oral gavage either immediately (early treatment) or 12 h after
      the surgical procedure (delayed treatment). Both early and delayed ALA treatment
      effectively prolonged survival, improved pathological damage in kidney tissues
      and reduced serum blood urea nitrogen and creatinine levels in CLP-induced septic
      rats. Furthermore, early treatment with ALA markedly inhibited the release of
      tumour necrosis factor-alpha, interleukin (IL)-6 and IL-1beta into the serum and
      reduced mRNA and protein expression of inducible nitric oxide synthase and high
      mobility group box 1 in kidney tissues from CLP-induced rats. Finally, CLP
      induced nuclear factor-kappaB activation in kidney tissues was significantly
      suppressed by early ALA treatment. Together, the results indicate that ALA is
      able to reduce mortality and attenuate acute kidney injury associated with
      sepsis, possibly by anti-inflammatory actions. alpha-Lipoic acid may be a
      promising novel agent for the treatment of conditions associated with septic
      shock.

PMID- 24738480
TI  - Distinguishing torpedo maculopathy from similar lesions of the posterior segment.
AB  - Torpedo maculopathy is a congenital solitary, oval-shaped lesion typically
      located temporal to the center of the macula. Congenital hypertrophy of the
      retinal pigment epithelium (RPE), RPE lesions of Gardner syndrome, and other
      lesions can present with similar characteristics. Because of its unique clinical
      and imaging features, torpedo maculopathy generally can be differentiated from
      other posterior segment lesions.

PMID- 24738481
TI  - The scientific world revolves around the word evidence.

PMID- 24738483
TI  - Glucocorticoids in juvenile idiopathic arthritis.
AB  - Although the use of corticosteroids in juvenile idiopathic arthritis (JIA) is now
      much more limited owing to the availability of methotrexate and biological
      agents, there are clinical scenarios where it is still indicated. For example,
      corticosteroids may be indicated for intraarticular injections to prevent joint
      deformities, as a "bridge" drug to relieve symptoms in polyarticular disease
      while waiting for methotrexate and biologics to exert their full therapeutic
      effects, and in the treatment of chronic iridocyclitis, macrophage activation
      syndrome, and systemic JIA, although the advent of interleukin (IL)-1 and IL-6
      blockers has greatly reduced the latter indication. 

PMID- 24738484
TI  - Childhood obesity trends: time for champagne?

PMID- 24738485
TI  - Enhanced humoral and cell-mediated immune responses generated by cationic polymer
      coated PLA microspheres with adsorbed HBsAg.
AB  - Surface-engineered particulate delivery systems for vaccine administration have
      been widely investigated in experimental and clinical studies. However, little is
      known about charge-coated microspheres as potential recombinant subunit protein
      antigen delivery systems in terms of adsorption and related immune responses. In
      the present study, cationic polymers, including chitosan (CS), chitosan chloride
      (CSC), and polyethylenimine (PEI), were used to coat PLA microspheres to build
      positively charged surfaces. Antigen adsorption capacity was enhanced with
      increased surface charge of coated microspheres. In macrophages, HBsAg adsorbed
      on the surface of cationic microspheres specifically enhanced antigen uptake and
      augmented CD86, MHC I, and MHC II expression and IL-1beta, IL-6, TNF-alpha, and
      IL-12 release. Antigens were more likely to localize independent of lysosomes
      after phagocytosis in antigen-attached cationic microsphere formulations. After
      intraperitoneal immunization, cationic microsphere-based vaccine formulations
      generated a rapid and efficient humoral immune response and cytokine release as
      compared with aluminum-adsorbed vaccine and free antigens in vivo. Moreover,
      microspheres coated with cationic polymers with relatively high positive charges
      and higher antigen adsorption exhibited strong stimulation of the Th1 response.
      In conclusion, PLA microspheres coated with cationic polymers may be a potential
      recombinant antigen delivery system to induce strong cell and humoral immune
      responses.

PMID- 24738486
TI  - Dextran-based hydrogel microspheres obtained in w/o emulsion: preparation,
      characterisation and in vivo studies.
AB  - The cross-linking reaction in w/o emulsions of dextran (DEX) functionalised with
      methacrylic groups, having or not acid residues in side chain, can be used to
      easily prepare polysaccharide hydrogel microspheres with properties suitable for
      drug delivery applications. The formation of a chemical network within the
      obtained particles was evaluated with FT-IR spectroscopy, whereas morphology and
      dimensions of the microspheres were investigated with optical and scanning
      electron microscopy. At the same time, swelling measurements were carried out on
      freeze-dried particles in different aqueous media simulating biological fluids.
      Preliminary release experiments performed with ibuprofen, betamethasone and
      vitamin B12 chosen as model drugs, showed that these microspheres could be
      suitable as modified drug delivery systems in oral formulations. Finally, in vivo
      writhing experiments were carried out in mice in order to verify the
      antinociceptive activity of betamethasone loaded into the new polysaccharide
      hydrogel microspheres.

PMID- 24738487
TI  - Design and analysis of clinical trials of nutrients: author reply.

PMID- 24738488
TI  - Mutational analysis of FUS gene and its structural and functional role in
      amyotrophic lateral sclerosis 6.
AB  - Amyotrophic lateral sclerosis 6 (ALS6) is an autosomal recessive disorder caused
      by heterozygous mutation in the Fused in Sarcoma (FUS) gene. ALS6 is a
      neurodegenerative disorder, which affects the upper and lower motor neurons in
      the brain and spinal cord, resulting in fatal paralysis. ALS6 is caused by the
      genetic mutation in the proline/tyrosine-nuclear localization signals of the
      Fused in sarcoma Protein (FUS). FUS gene also known as TLS (Translocated in
      liposarcoma), which encodes a protein called RNA-binding protein-Fus (FUS), has a
      molecular weight of 75 kDa. In this analysis, we applied computational approach
      to filter the most deleterious and neurodegenerative disease of ALS6-associated
      mutation on FUS protein. We found H517Q as most deleterious and disease
      associated using PolyPhen 2.0, I-Mutant 3.0, SIFT, SNPs&GO, PhD-SNP, Pmut, and
      Mutpred tools. Molecular dynamics simulation (MDS) approach was conducted to
      investigate conformational changes in the mutant protein structure with respect
      to its native conformation. MDS results showed the flexibility loss in mutant
      (H517Q) FUS protein. Due to mutation, FUS protein became more rigid in nature and
      might alter the structural and functional behavior of protein and play a major
      role in inducing ALS6. The results obtained from this investigation would help in
      the field of pharmacogenomics to develop a potent drug target against FUS
      associated neurodegenerative diseases. 

PMID- 24738489
TI  - Evaluating the contributions of culture and cultural fit in evidence-based
      programs: a commentary.
AB  - This commentary provides a critical review of the articles in this special
      section. The extent to which culture and cultural fit are active ingredients for
      developing and establishing culturally robust preventive interventions for
      children and families of color are considered. Implications of research in this
      area for determining how to effectively capture the nuances of culture in family
      based preventive interventions are noted. 

PMID- 24738490
TI  - The age effect on the association between the scavenger receptor class B type I
      (SR-BI) polymorphism and HDL-C level: Tehran Lipid and Glucose Study.
AB  - INTRODUCTION: The scavenger receptor class B type I (SR-BI) is a key component in
      the reverse cholesterol transportation. The aim of this study was to assess the
      association between exon1 (G -> A) polymorphism of SR-BI gene and lipid profiles
      among the Tehran Lipid and Glucose Study (TLGS) population. MATERIALS AND
      METHODS: This cross-sectional study included 774 adults (322 males and 452
      females) aged 20-70 years who were randomly selected from among TLGS population.
      Anthropometrical and biochemical variables for participants were measured.
      Selected SR-BI gene polymorphism was determined with restriction fragment length
      polymorphism, via Alu restriction enzyme. RESULTS: Minor allele frequency for SR
      BI polymorphism in the selected population was 0.159. Allele frequencies were in
      conformity with Hardy-Weinberg equilibrium. Association between (G -> A) SR-BI
      polymorphism and high density lipoprotein cholesterol (HDL-C) and HDL3 was
      significant only after adjustment for age as a potential covariate (p = 0.046,
      0.041, respectively); however, the results did not improve after adjustment for
      sex. DISCUSSION: The result of this study confirms the role of age as a potential
      confounder which could modify the association between the SR-BI single nucleotide
      polymorphism and HDL-C level.

PMID- 24738491
TI  - Magnetic field effects on copper metal deposition from copper sulfate aqueous
      solution.
AB  - Effects of a magnetic field (<=0.5 T) on electroless copper metal deposition from
      the reaction of a copper sulfate aqueous solution and a zinc thin plate were
      examined in this study. In a zero field, a smooth copper thin film grew steadily
      on the plate. In a 0.38 T field, a smooth copper thin film deposited on a zinc
      plate within about 1 min. Then, it peeled off repeatedly from the plate. The
      yield of consumed copper ions increased about 2.1 times compared with that in a
      zero field. Mechanism of this magnetic field effect was discussed in terms of
      Lorentz force- and magnetic force-induced convection and local volta cell
      formation. 

PMID- 24738492
TI  - Antinuclear antibodies in atopic dermatitis: a cross-sectional study on 346
      children.
AB  - BACKGROUND: Atopic dermatitis (AD) is a chronic inflammatory skin disease that
      can be classified into an extrinsic or intrinsic type. A high percentage of
      patients, especially adults with the extrinsic type of AD, have been reported to
      show antibodies to antinuclear proteins (ANA). We aimed to study the prevalence
      of ANA in children with AD and to evaluate clinical differences between patients
      with ANA-positive and ANA-negative AD. METHODS: A total 346 serum samples from
      children with active AD (mean age 5.8 years) and 117 hospital controls without
      known skin, inflammatory, or immune-mediated disease (mean age 7.9 years) were
      tested for IgG ANA with indirect immunofluorescence on HEp-2 cells, total serum
      IgE levels, and IgE type antibodies to food allergen panels. RESULTS: In total,
      47 patients with AD (13.6%) and 15 subjects in the control group (12.8%) were ANA
      positive at screening dilution 1:10 (P > 0.05). In patients with AD, ANA was
      found already at the age of 2 years, significantly more often in females (P <
      0.005) and at slightly higher titers (up to 1:160). No differences were found in
      ANA positivity regarding the severity of AD or sensitization to food allergens.
      CONCLUSION: No significant differences were observed between AD and the control
      group, or between different subtypes of AD in ANA prevalence. In both groups, ANA
      frequency increased with age, but in patients with AD, ANA had a tendency to
      appear earlier. Therefore, active AD during the early years of life could dispose
      selected patients towards earlier development of systemic autoreactivity and
      stress the need for regular follow-up of patients with ANA-positive AD.

PMID- 24738494
TI  - Health care workers and ICU pain perceptions.
AB  - OBJECTIVE: Our study examined the effect of health care workers' personal
      characteristics on how they perceive and intend to treat patients' pain in the
      intensive care unit. Though pain perceptions have been well established from the
      patient's perspective, less is known about how variations in health care workers
      may affect their perceptions of pain. DESIGN: This study consisted of a 28-item
      questionnaire distributed to 122 medical staff personnel over a 12-month period.
      The questionnaire included items regarding respondent characteristics such as
      age, gender, race, ethnicity, and level of training. SUBJECTS AND SETTING: The
      questionnaire was distributed to physicians and nurses working in the critical
      care setting. METHODS: Responses were provided using a Likert scale and scored on
      subscales of hemodynamic instability, addiction and tolerance, pain expression,
      legal issues, and education. RESULTS: The results demonstrated that
      characteristics such as age and race were significant predictors of perceptions
      regarding addiction subscale scores (beta = -0.256, P = 0.006 and beta = 0.183, P
      = 0.053, respectively). Race proved to be a significant factor in pain expression
      scores (beta = 0.183, P = 0.053). Work-related variables, such as being in or out
      of active medical training and being within the critical care specialty itself,
      were significant predictors of addiction subscale scores as well (beta = -0.238,
      P = 0.012 and beta = 0.191, P = 0.050, respectively). CONCLUSION: Health care
      providers' race, age, level of education, and medical subspecialty were
      significant factors affecting their perceptions of pain management and intended
      treatment.

PMID- 24738493
TI  - Assessment of magnetic resonance techniques to measure muscle damage 24 h after
      eccentric exercise.
AB  - The study examined which of a number of different magnetic resonance (MR) methods
      were sensitive to detecting muscle damage induced by eccentric exercise.
      Seventeen healthy, physically active participants, with muscle damage confirmed
      by non-MR methods were tested 24 h after performing eccentric exercise.
      Techniques investigated whether damage could be detected within the quadriceps
      muscle as a whole, and individually within the rectus femoris, vastus lateralis
      (VL), vastus medialis (VM), and vastus intermedius (VI). Relative to baseline
      values, significant changes were seen in leg and muscle cross-sectional areas and
      volumes and the resting inorganic phosphate concentration. Significant time
      effects over all muscles were also seen in the transverse relaxation time (T2)
      and apparent diffusion coefficient (ADC) values, with individually significant
      changes seen in the VL, VM, and VI for T2 and in the VI for ADC. A significant
      correlation was found between muscle volume and the average T2 change (r = 0.59)
      but not between T2 and ADC or Pi alterations. There were no significant time
      effects over all muscles for magnetization transfer contrast images, for baseline
      pH, phosphocreatine (PCr), phosphodiester, or ATP metabolite concentrations or
      the time constant describing the rate of PCr recovery following exercise.

PMID- 24738495
TI  - Real-time PCR for quantification in soil of glycoside hydrolase family 6
      cellulase genes.
AB  - Cellulose is the main structural component of the cell walls of higher plants,
      representing c. 35-50% of a plant's dry weight; after decomposition and
      transformation, and constituting a large part of soil organic matter. Telluric
      micro-organisms able to use cellulose as carbon and energy sources for growth are
      widely distributed in the environment, but the factors controlling the rate of
      cellulose degradation are not well understood. In this study, we have developed a
      quantitative real-time PCR (qPCR) primer set to quantify the glycoside hydrolase
      family 6 (GH6 family) cellulase genes in soil samples. The qPCR assays were
      linear over 8 orders of magnitude and sensitive down to 10 copies per assay. qPCR
      analysis of contrasted soil samples showed densities between 2.47 * 10(7) and
      1.48 * 10(10) copies per gram of soil. Cloning and sequencing of the PCR products
      from environmental DNA confirmed both specific amplification (more than 96%) and
      the wide diversity targeted by the primer set, throughout nearly all the GH6
      family, including sequences of bacteria and fungi. SIGNIFICANCE AND IMPACT OF THE
      STUDY: Telluric micro-organisms able to use cellulose as carbon and energy
      sources for growth are widely distributed in the environment, but the factors
      controlling the rate of cellulose degradation are not well understood. The
      objective of our study was to develop a qPCR for rapid quantification of GH6
      cellulase genes in soil. This qPCR could be applied to study the potential for
      cellulose degradation in different soils in order to better understand the
      factors controlling the stability of the soil organic matter.

PMID- 24738496
TI  - Predictors of environmental lead exposure among pregnant women - a prospective
      cohort study in Poland.
AB  - Blood lead levels (BLL) in women of child-bearing age have been decreasing in
      recent decades, but still remains a concern for long-term effects of child
      psychomotor development. The aim of the study was to characterize lead exposure
      among Polish pregnant women and assess the relationship between BLL and selected
      socio-demographic, economic and lifestyle factors. The study population consisted
      of 594 pregnant women who had been the subjects of the prospective Polish Mother
      and Child Cohort Study (REPRO_PL). The women were interviewed three times during
      pregnancy (once in each trimester. Lead concentration in the blood collected
      during the second trimester of pregnancy was analyzed using graphite furnace
      atomic absorption spectrometry (GF-AAS), or inductively coupled plasma mass
      spectrometry (ICP-MS). Active and passive smoking was analyzed by the cotinine
      level in saliva using liquid chromatography with tandem mass spectrometry (LC
      MS/MS). The lead level in the blood ranged from 0.3 - 5.7 MUg/dL, with a
      geometric mean (GM) of 1.1 MUg/dL (GSD +/-0.2 MUg/dL). Statistically significant
      associations were found between BLL and factors such as maternal age (beta=0.01;
      p=0.02), education (beta=0.08; p=0.04) and prepregnancy BMI (beta=0.1; p=0.001).
      Additionally, BLL increased with increasing cotinine level in saliva (beta=0.02;
      p=0.06) and decreased with the increasing distance from the copper smelter (beta=
      0.1; p=0.009). Public health interventions, especially in regions with a higher
      level of exposure to lead, among women with lower SES and among smokers, are
      still reasonable.

PMID- 24738497
TI  - Epidemiology of sarcoidosis recorded in 2006-2010 in the Silesian voivodeship on
      the basis of routine medical reporting.
AB  - INTRODUCTION AND OBJECTIVE: The incidence of sarcoidosis (D.86.0, D.86.2) varies
      worldwide, although published data suggest that the rate remains at the level 10
      40/100 000 population. In Poland, statistics are not conducted on sarcoidosis.
      The etiology of the disease remains unclear, but researchers suggest that one of
      causes is the exposure to environmental factors. The aim of this study is to
      determine territorial and temporal variations of incidence and hospitalized
      prevalence of sarcoidosis for adults aged 19 and older living in the Silesian
      voivodeship in south-western Poland. MATERIALS AND METHODS: To identify the
      number of cases of sarcoidosis and the number of hospitalized patients in 2006
      2010, the database of the National Health Fund in Katowice, Silesia, was used.
      Data related to adults aged 19 and older who were inhabitants of the Silesian
      voivodeship. Standardized incidence and prevalence rates for total sarcoidosis
      per 100,000 population were calculated using the world standard population.
      Temporal and spatial variability of both rates in the Silesian voivodeship were
      presented according to ArcGIS 9.2. RESULTS: The number of new cases of
      sarcoidosis is still increasing. The disease occurred primarily in younger men
      (25-50 years of age), as well as in some older women (age group 50-64 years).
      Standardized incidence rates of total sarcoidosis are in the range 3.8
      4.5/100,000 population. There was a probable relationship between the incidence
      of sarcoidosis and the area of forest (r=0.4) or arable land (r=0.3).
      CONCLUSIONS: Sarcoidosis is a rare disease in the Silesian voivodeship and the
      standardized incidence and prevalence rates are slightly higher in men than in
      women. In the study period, spatial variability was observed. The highest rates
      were typical for districts with a predominance of forests and arable land.

PMID- 24738498
TI  - Exposure to environmental factors and relationship to allergic rhinitis and/or
      asthma.
AB  - INTRODUCTION AND OBJECTIVES: Studies analyzing risk factors, multiple indoor and
      outdoor factors related to asthma and/or allergic rhinitis (AR) in childhood, are
      very rare. The presented study was carried out to simultaneously assess host
      related, indoor and particulate matter exposure with current allergic rhinitis
      (AR) and/or asthma in children (6-7 years) and adolescents (13-14 years).
      MATERIAL AND METHODS: The method was a cross-sectional population-based study in
      which participants were diagnosed by means of the International Study of Asthma
      and Allergies in Childhood (ISAAC) written questionnaire. RESULTS: Exposure to
      indoor risk factors were verified in 1,302 individuals, in which the prevalence
      of AR, asthma and AR-asthma comorbidity were 37.3%, 28.4%, and 16%, for children
      and 31.5%, 16.2%, and 10.5% for adolescents, respectively. Smoking during
      pregnancy was associated with current asthma (OR=1.5), second-hand smoking with
      AR-asthma comorbidity (OR=1.4) and visible mold on the walls with current AR,
      asthma, and AR-asthma comorbidity (OR=1.6). In a subgroup of 590 children, in
      addition to the indoor risk factors, exposure to PM10 was assessed. In this joint
      analysis, there was association with the same previously mentioned risk factors
      (p values <= 0.5) and a negative association to PM10 (p <= 0.002). CONCLUSION:
      The results suggest that avoidance of smoking during pregnancy, second-hand
      smoking and exposure to mould at home can contribute to reducing current AR
      and/or current asthma. Exposure to PM10 was not associated with the prevalence
      rate of these diseases.

PMID- 24738499
TI  - Clinical relevance of Corylus pollen in Poznan, western Poland.
AB  - BACKGROUND: In Central Europe, hazel (Corylus sp.) pollen is considered to be an
      important aeroallergen in early spring. OBJECTIVE: This study examines hazel
      pollen levels in Poznan, western Poland, and the clinical relevance of this
      aeroallergen in the city. METHODS: Corylus pollen data (1996-2010) were obtained
      by volumetric spore trap located near the centre of Poznan. Clinical data (2006
      2010), i.e. skin prick test (SPT) and allergen-specific IgE measurements (asIgE),
      were supplied by the Allergy Diseases Diagnostic Centre in Poznan. RESULTS: Mean
      diurnal hazel pollen concentrations peaked around 14:00-16:00 when mean bi-hourly
      pollen concentrations were ~60 P m(-3). Onset of the hazel pollen season varied
      up to 87 days annually, and was significantly (r=-0.647; p<0.01) related to mean
      maximum temperature during late December. SPT data revealed that ~11% of allergy
      patients had positive skin reactions to Corylus pollen allergens, and most of
      these (94.4%) reacted to pollen allergens from other members of the Betulaceae
      family - alder or birch. Of those sensitized, 53% suffered from atopic
      dermatitis. Of patients examined for serum asIgE, 26.0% had asIgE measurements in
      classes 5 and 6. CONCLUSIONS: Hazel pollen has a detrimental effect on the
      allergic population of Poznan, with more than half of those sensitised to hazel
      pollen allergens showing symptoms of atopic dermatitis. Hazel pollen
      concentrations reach levels recognized as being able to induce allergy symptoms,
      especially in the afternoon and early evening when many people are returning home
      from work. The cross-reactivity with other members of the Fagales order also
      increases the allergenic potential of hazel pollen.

PMID- 24738500
TI  - Common ophthalmic problems of urban and rural postmenopausal women in a
      population sample of Raciborz district, a RAC-OST-POL Study.
AB  - INTRODUCTION AND OBJECTIVE: We wished to establish the prevalence of eye diseases
      and eye disease risk factors at postmenopausal age and to compare ophthalmic
      problems in urban and rural areas of Raciborz. PATIENTS AND METHODS: The study
      was performed in 2010. Out of the whole population of Raciborz, Poland, 10
      percent (1750) of women were randomly selected for the reported study. Finally,
      ocular diseases, ophthalmic agents, health status (physical activity level, body
      mass index - BMI, reproductive history, the use of psychotropic drugs and hormone
      replacement therapy - HRT) were recorded in 623 women. The women underwent visual
      acuity test and anterior segment examination, applanation tonometry and indirect
      ophthalmoscopy. RESULTS: The mean age of the selected patients was 66.01 +/- 7.76
      years, 275 (44%) of them originating from rural and 348 (56%) from urban regions.
      The average woman was obese (BMI=30.54 +/- 5.38 kg/m(2)), with near normal
      agility and reproductive history of 2.59 +/- 1.55 births, 147 (24%) subjects
      remained under regular HRT support. According to the WHO, the visual acuity was
      classified as normal or near normal in 87.5%, while no blindness was recorded at
      all. Visual acuity depended, first of all, on lens status and was better among
      subjects with good agility (R=-0.31, p=0.001). Dry eye prevalence increased
      significantly over age of 67 years (p=0.000) and HRT seemed to be a dry eye
      protective factor (p=0.010). Except age, No other risk factors of cataract, other
      than age, were identified. Normal agility (p=0.003) and HRT (p=0.032) were
      associated with lower AMD (age-related macular degeneration) prevalence rates.
      The differences between urban and rural participants were presented only in
      education, reproductive history, hypertension and frequency of ophthalmic
      examinations. CONCLUSIONS: Older adult women living in neighboring urban and
      rural areas present no differential in ophthalmic health problems.

PMID- 24738501
TI  - Level and determinants of physical activity among school adolescents in Poland.
AB  - The recognition of adolescents' physical activity has become one of the serious
      challenges of the modern times, as a concern about the future health of
      societies. The major goal of the presented study was to discover the level of
      physical activity among Polish adolescents aged 16-18, and the factors which
      condition this level. The investigations were carried out in 2011, among 2,974
      school adolescents from various locations in Poland - 1,790 girls (60.2%), and
      1,184 boys (39.8%). As a study method, a short version of the IPAQ was applied.
      The results of the study indicated that a larger number of girls than boys show a
      low level of physical activity. With respect to activity among boys, higher
      values of intensive and moderate efforts are noted, while in girls, higher values
      of activities related to walking. It was confirmed that the level of physical
      activity does not depend on the place of residence. However, the number of
      physical exercise classes attended is a significant factor, both among boys and
      girls. It was also found that adolescents who more frequently lead a sedentary
      style of life are characterized by a lower level of total physical activity.
      Sedentary lifestyle (time spent sitting) does not differ among the level of
      physical activity of girls and of boys, neither with respect to the scope of the
      total physical activity nor to its three levels (low, moderate, high).

PMID- 24738502
TI  - Demographic and health situation of children in conditions of economic
      destabilization in the Ukraine.
AB  - INTRODUCTION AND OBJECTIVE: In new conditions of socio-economic development in
      the Ukraine, the health of the population of children is considered as the most
      reliable indicator of socio-economic development of the country. The primary goal
      of the study was analysis of the effect of contemporary socio-economic
      transformations, their scope, and strength of effect on the demographic and
      social situation of children in various regions of the Ukraine. The
      methodological objectives of the study were as follows: development of a
      synthetic measure of the state of health of the population of children, based on
      the Hellwig's method, and selection of districts in the Ukraine according to the
      present health-demographic situation of children. MATERIAL AND METHODS: The study
      was based on statistical data from the State Statistics Service of Ukraine,
      Centre of Medical Statistics in Kiev, Ukrainian Ministry of Defence, as well as
      Ministry of Education and Science, Youth and Sports of Ukraine. The following
      research methods were used: analysis of literature and Internet sources,
      selection and analysis of statistical materials, cartographic and statistical
      methods. RESULTS AND CONCLUSIONS: Basic indices of the demographic and health
      situation of the population of children were analyzed, as well as factors of a
      socio-economic nature which affect this situation. A set of variables was
      developed for the synthetic evaluation of the state of health of the population
      of children. The typology of the Ukrainian districts was performed according to
      the state of health of the child population, based on the Hellwig's taxonomic
      method. Deterioration was observed of selected quality parameters, as well as a
      change in the strength and directions of effect of factors of organizational
      institutional, socioeconomic, historical and cultural nature on the population of
      children potential.

PMID- 24738503
TI  - HPLC analysis of potentially harmful substances released from dental filing
      materials available on the EU market.
AB  - INTRODUCTION: Incomplete cross-linking of composite dental materials leads to
      their susceptibility to degradation in the environment of non-organic and organic
      solvents, contributing to the release of chemical compounds which are potentially
      harmful to living organisms. OBJECTIVE: The aim of the study was an evaluation in
      in vitro conditions of releasing of potentially toxic substances from six dental
      composite materials available in EU countries. MATERIALS AND METHODS: The
      following compounds released from the samples stored in water were analyzed:
      bisphenol A (BPA), triethylene glycol-dimethacrylate (TEGDMA), urethane
      dimethacrylate (UDMA) and ethylene glycol dimethacrylate (EDGMA). Analysis of the
      substances was performed with the use of high performance liquid chromatography,
      after the following incubation periods: 1 hour, 24 hours, 7 days and 30 days.
      RESULTS: Among the analyzed substances, after 1 hour of incubation, the highest
      average concentration was found for TEGDMA - 2045 MUg cm(-3) (in Herculite XRV
      material), after 24 hours - for UDMA 4.402 MUg cm(-3) (in Gradia Direct Anterior
      material) and after 7 and 30 days for TEGDMA: 8.112 and 6.458 MUg*cm(-3)
      respectively (in Charisma material). CONCLUSIONS: The examined composites used
      for reconstruction of hard tissues of teeth remain chemically unstable after
      polymerization, and release potentially harmful substances in conditions of the
      present study. The dynamics of the releasing of potentially harmful substances is
      correlated with the period of sample storage in water.

PMID- 24738504
TI  - Intensification of anxiety and depression, and personal resources among women
      during the peri-operative period.
AB  - AIM: Surgical treatment of women due to gynaecological disorders is the cause of
      stress and may lead to psychological changes. Studies concerning human response
      to stress emphasize the importance of the effect of the level of the sense of
      coherence, anxiety, depression, dispositional optimism and skills of expressing
      emotions on the quality of feelings and experiences in difficult situations.
      MATERIALS AND METHODS: The study covered 232 women who had undergone
      gynaecological surgery due to various causes. Permission to conduct the research
      was obtained from the Bioethical Commission at the Medical University in Lublin.
      The study was carried out with the use of the State-Trait Anxiety Inventory
      (STAI), the Beck Depression Inventory, Courtauld Emotional Control Scale (CECS),
      and Life Orientation Test - Revised (LOT-R). RESULTS AND CONCLUSIONS: The study
      showed that investigations of the sense of coherence, level of anxiety and
      depression, and personal resources allow determination of the characteristics of
      patients who should be covered with special psycho-prophylactic care during the
      peri-operative period. In addition, the results of own studies obtained may be
      used for the development of adequate principles of psycho-prophylactic management
      in the course of the diagnostic-treatment process with respect to women who had
      undergone surgical treatment due to gynaecological disorders.

PMID- 24738505
TI  - The monitoring of mineral elements content in fruit purchased in supermarkets and
      food markets from Timisoara, Romania.
AB  - This study aimed at evaluating various fruit samples using atomic absorption
      spectrometry method, the content in mineral elements, macroelements (Na, K, Ca,
      Mg) and microelements (Cr, Cu, Mn, Fe, Cd , Pb, Zn, Co and Ni). Fruit samples
      were taken from supermarkets (imported products) and agricultural markets
      (domestic products) in the city of Timisoara, Romania. The results obtained by
      chemical analysis were evaluated statistically based on method of main components
      analyzed. Major influence in the group had evidence if macroelements potassium
      and sodium, iron and manganese where microelements. The results were compared
      with results obtained by other researchers in the world. The results fall within
      the legal limits set by law.

PMID- 24738506
TI  - Effect of exercise on Special Aviation Gymnastics Instruments on blood serum
      levels of selected biochemical indices in cadets.
AB  - INTRODUCTION: Aim of this study was the training effect evaluation on the Special
      Aviation Gymnastics Instruments (SAGI) on blood metallothionein (MT), zinc (Zn),
      copper (Cu), protein, neuron-specific enolase (NSE), and physical fitness in the
      examined cadets. MATERIAL AND METHODS: The study comprised 55 cadets, aged 20,
      divided into two groups: examined group A (N=41) and control group B (N=14). In
      both groups, blood material was collected twice, i.e. before (baseline) and after
      training (series I), during (series II), and after completion of training on the
      SAGI (Series III). Blood serum MT, Zn, Cu, protein, and NSE were assayed with
      commercially available kits). Physical fitness was assessed with commonly used
      fitness tests. RESULTS: A significant decrease in serum MT was noted in both
      groups in all three series of assays after training, except group B in series II.
      NSE significantly increased in group A in series II after training. NSE activity
      increased significantly in group B in series I and III. In both groups, a
      significant decrease in blood serum Zn was noted after training in series I and
      II. Serum Cu significantly decreased in group A in all three series of assays.
      Blood serum protein significantly decreased in group A in series III. In series
      II, blood serum protein increased significantly in both groups. The remaining
      values were not changed significantly. CONCLUSIONS: Training intensity on SAGI
      lowered serum MT levels after training in comparison with the control group. This
      might be associated with Zn, Cu, and protein metabolism.

PMID- 24738507
TI  - Non-alcoholic beverages, unknown influence on cell proliferation - an in vitro
      study.
AB  - INTRODUCTION AND OBJECTIVE: The aim of the presented study was to check
      differences between 'Diet' and 'non-Diet' soft drinks on cell proliferation.
      MATERIALS AND METHODS: Coca Cola and Pepsi Cola of different origin and their
      dietetic versions were examined at concentrations of 2% and 4%. Fructose and
      glucose as well as medium alone (control) were examined. RESULTS: Cell number was
      higher in media supplemented with soft drinks, compared to control. Proliferation
      depended on the soft drink concentration and its origin, but not on sugar and
      calorific content. CONCLUSIONS: An unknown factor is responsible for the increase
      in proliferation.

PMID- 24738508
TI  - Underweight in 14 to 16 year-old girls and boys: prevalence and associations with
      physical activity and sedentary activities.
AB  - INTRODUCTION AND OBJECTIVES: Underweight is associated with increased mortality
      of adults when compared to normal weight or overweight individuals. Studies of
      associations between underweight and physical activity levels in adolescents are
      sparse. The aim of this study was to determine the prevalence of underweight
      amongst 14 to 16 year-old girls and boys in tandem with the levels of physical
      activity and time spent in sedentary activities. The results were compared to
      those observed in normal weight and overweight adolescents. MATERIAL AND METHODS:
      This study included 1702 girls and 1547 boys aged from 14 to 16 years from twelve
      gymnasium schools in Poznan (Poland). Based on BMI values, the participants were
      assigned to the following categories: a) underweight, b) normal weight, and c)
      overweight. The levels of physical activity, participation rates in physical
      education classes and the time spent in sedentary activities were determined by
      means of questionnaire survey. RESULTS: The fraction of underweight girls
      amounted to 11.6% and was similar to the percentage of obese girls (14.6%). The
      fraction of underweight boys was 7.0%, and was markedly lower than the percentage
      of overweight boys (17.0%). Underweight and overweight boys were characterized by
      significantly lower levels of physical activity compared to normal weight
      participants (p <=.001). Both in girls and in boys, the prevalence of underweight
      and overweight was not significantly associated with the time spent in various
      sedentary activities. CONCLUSIONS: Underweight occurs in relatively high fraction
      of girls and boys. Underweight is associated with lower levels of physical
      activity in boys. The prevalence of underweight among adolescents is not
      associated with time spent in sedentary activities.

PMID- 24738509
TI  - Alcohol- and water-based extracts obtained from Rhodiola rosea affect differently
      the number and metabolic activity of circulating granulocytes in Balb/c mice.
AB  - INTRODUCTION AND OBJECTIVE: Rhodiola rosea (RR) rhizomes with roots extracts are
      traditional natural drugs originated from Asia and now commonly used as
      adaptogens and antidepressants. The aim of this work was to study the in vivo
      effect of aqueous (RRW) and 50% hydro-alcoholic (RRA) extracts on the number and
      metabolic activity of blood granulocytes in mice. MATERIAL AND METHODS: Mice were
      fed for 7 days RR extract in daily doses 0.05, 0.1, 0.2 or 0.4 mg. The metabolic
      activity of blood granulocytes was determined by measuring of their luminol
      dependent chemiluminescent activity in scintillation counter, after zymosan
      stimulation. RESULTS: Number of blood granulocytes was diminished and their
      chemiluminescence was enhanced in all groups of mice fed R.rosea hydro-alcoholic
      extract. Aqueous extract (RRW) was ineffective in all doses applied. CONCLUSION:
      This study revealed difference in the number and metabolic activity of
      granulocytes mice fed RRA or RRW extracts. Immune characteristics of some
      individual compounds from RRA and RRW extracts, selected by HPLC analysis, should
      be carried out in the next experiments.

PMID- 24738510
TI  - Salt caves as simulation of natural environment and significance of halotherapy.
AB  - INTRODUCTION: Human activity usually leads to a deterioration in air quality;
      therefore, searching for places that simulate an environment without pollution is
      important. Artificial salt caves play crucial role, as a kind of therapy, known
      as halotherapy, based on treatment in a controlled air medium that simulates a
      natural salt cave microclimate. OBJECTIVE: Evaluation of awareness about the
      existence of salt caves, basic knowledge about the purpose for their presence
      among people who bought salt caves sessions, and checking their subjective
      estimation of salt caves influence on their well-being. MATERIAL & METHODS: 303
      inhabitants (18-51-years-old) of 3 randomly chosen cities of southern Poland were
      surveyed using a validated author's questionnaire. Both genders were represented
      in comparable numbers. RESULTS: It was be observed that knowledge about the
      existence of salt-caves is common - 94% of respondents. 96 persons bought at
      least 3 salt caves sessions. The majority of women, did this for therapeutic
      reasons (57%), and men for both therapeutic and relaxation reasons (both 39%).
      Both among women and men, the dysfunctions intended to be cured by sessions
      included problems with throat, larynx or sinus. Depression as a reason for buying
      sessions was mentioned only by women. In general, those who attended felt better
      after sessions in salt caves. CONCLUSION: Besides the health benefits, people do
      not have free time for rest and activities in clean air; moreover, stress is
      inseparable from everyday life, and for that reasons salt caves become places
      that help to support a proper lifestyle.

PMID- 24738511
TI  - Dietary habits among persons hired on shift work.
AB  - INTRODUCTION: Shift-work determinates irregular nutrition habits. The quality as
      well as the quantity of meals consumed by shift-workers can significantly affects
      their health. OBJECTIVE: The aim of this study was to evaluate the dietary habits
      of people performing shift work in the Bogdanka mine. MATERIAL AND METHODS: The
      study was carried out in the Bogdanka mine in Leczna. The questionnaire, which
      was designed by the author of this dissertation, was conducted among 700 shift
      workers, working underground. The results were subjected to statistical analysis
      based on STATISTICA v. 7.1 (StatSoft, Poland) software. RESULTS: Nearly half of
      respondents reported regular consumption of meals (40.0%) Interviewees admitted
      having warm meals during the day (81.4%). The most frequently consumed meal
      during the day was the hot one (50.9%), three meals and more were consumed the
      least frequently (8.1%). Almost half of respondents considered their eating
      habits as inappropriate (46.3%). Among those, nearly half (68.2%) stated that
      shift - work is the reason for their nutrition habits. More than half of
      respondents (66.0%) admitted that shift work hampers regular consumption of
      meals. CONCLUSIONS: Shift work makes nourishment and regular consumption
      difficult. It contributes to the limited amount of warm meals eaten during the
      day. In order to maintain preventive health care and the improvement of quality
      of life, shift workers should be provided with an easier access to meals
      (including warm one) at specified times of the day.

PMID- 24738512
TI  - Relationship between renalase and N-terminal pro-B-type natriuretic peptide (NT
      pro-BNP) in haemodialysis patients.
AB  - INTRODUCTION: Our knowledge in the field of cause of deaths in dialysis patients
      is rapidly expanding, yet we still do not fully understand how renalase regulates
      the processes of cardiovascular disease developing in end-stage renal disease.
      Increased sympathetic nerve activity observed in chronic kidney diseases due to
      raised catecholamines in plasma results from the absence of renalase. Renalase
      synthesized and secreted by the kidneys participate in the regulation of
      sympathetic tone and blood pressure. A family of natriuretic peptides has been
      identified - NT pro-BNP - which seems to be the best predictor of clinical
      outcome and marker of extracellular fluid overload, as well as predicting
      mortality, irrespective of renal function. OBJECTIVE: The aim of the presented
      study was to investigate renalase concentration and investigate associations
      between NT-proBNP, as well as analyzed parameters in haemodialysis patients.
      MATERIALS AND METHOD: The study was conducted among residents of the municipality
      and neighbouring villages in the province of Lublin, central-eastern Poland. 49
      male subjects on haemodialysis, aged 65.3 +/- 14.2 years, median time on
      haemodialysis: 37.5 months, were included. All study subjects underwent
      haemodialysis 3 times a week. The mean concentration of renalase in the entire
      study population was 126.59 +/- 32.63 ng/mL. The circulating levels of NT-proBNP
      was 813.64 +/- 706.96 pg/mL. A significant inverse correlation was found between
      NT-proBNP and renalase plasma levels (R = -0.3, P = 0.03). CONCLUSIONS: Inverse
      correlation between NT-proBNP and renalase plasma levels in haemodialysis
      patients were due to impaired kidney function, accompanied by increased
      sympathetic nerve activity, which have an impact on the development of
      hypertension and cardiovascular complications.

PMID- 24738513
TI  - Influence of urbanization level and Gross Domestic Product on the prevalence of
      adolescent obesity in Poland.
AB  - INTRODUCTION: Obesity is considered as a major disease of twenty-first century
      civilization. Its occurrence in Poland and worldwide has been increasing steadily
      for many years. Several factors play an important role in the development of
      overweight and obesity. In addition to the genetic factors and those associated
      with diseases of the endocrine system and nervous system, the rapidly growing
      number of obese people is due to improper nutrition. OBJECTIVES: In this paper,
      authors attempt to justify the prevalence of obesity in Poland among the
      population of adolescent and young adults aged 15 - 29 years of age, depending on
      the urbanization level and Gross Domestic Product (GDP) per capita of
      voivodeships. METHODS: Voivodeships, as an entity of regional autonomy, were
      divided into two groups according to urbanization level and GDP per capita. From
      the total population of each voivodeship population, groups of overweight and
      obese people aged 15-29 were selected. The population group aged 15-29 was
      divided into male and female subgroups. Each subgroup was compared in the
      different voivodeships, depending on the urbanization level and GDP per capita.
      RESULTS: The study shows that there is a strong linear relationship between the
      prevalence of obesity and GDP per capita of each examined region. During the
      study, the correlation between the level of prevalence of obesity and
      urbanization level produced a negative result. CONCLUSION: The high level of
      regional economic development in the economic transformation states has a
      significant impact on the increase in the percentage of people with overweight
      and obesity in the population aged 15-29. Gender and place of residence (urban or
      rural areas) did not show significant correlation with the occurrence of
      overweight and obesity in the study group of the population.

PMID- 24738514
TI  - Correlation between atherogenic risk and adiponectin in gestational diabetes
      mellitus.
AB  - INTRODUCTION AND OBJECTIVE: Gestational diabetes mellitus (GDM) is a pregnancy
      complication which increases the risk for maternal and foetal complications
      during pregnancy, and also significantly increases the cardiovascular risk for
      women's health in the postpartum. Current literature provides contradictory
      information on the role of adiponectin (AdipoQ) in the course of GDM. The aim of
      the study was to measure AdipoQ concentration in blood of women with GDM and to
      find correlations between this adipokine and clinical and biochemical parameters
      of the atherogenic risk. MATERIAL AND METHODS: The GDM group included 50 women
      diagnosed with GDM between 24 - 28 weeks of gestation who underwent routine
      prenatal tests for GDM in compliance with the guidelines of the Polish Diabetes
      Association. All patients underwent clinical and laboratory evaluation at GDM
      diagnosis. Laboratory tests included serum AdipoQ concentration, fasting glucose
      and insulin, OGTT, lipid parameters, C-reactive protein and fibrinogen in serum.
      RESULTS: The GDM group showed significantly elevated fasting glucose, insulin,
      HOMA-IR values, total cholesterol, LDLcholesterol and triglicerydes as compared
      with the control group (p<0.05). The atherogenic index, CRP, fibrinogen in women
      with GDM were significantly higher than in the control group (p<0.05). AdipoQ
      concentrations did not differ significantly between the groups during gestation
      (p=0.7054). No correlations, except with the neonatal weight (r= - 0.29, p<0.05),
      were found between AdipoQ and the studied parameters. CONCLUSIONS: Based on the
      conducted studies, it may be conclude that women with early diagnosed and
      promptly treated GDM have a normal adiponectin level, although insulin resistant
      changes and increased cardiovascular risk in basic metabolic parameters are
      observed. Moreover, adiponectin does not reflect the atherogenic risk in pregnant
      women with GDM.

PMID- 24738515
TI  - Optimal body balance disturbance tolerance skills as a methodological basis for
      selection of firefighters to solve difficult rescue tasks.
AB  - The aim of this study is the methodology of optimal choice of firefighters to
      solve difficult rescue tasks. 27 firefighters were analyzed: aged from 22-50
      years of age, and with 2-27 years of work experience. Body balance disturbance
      tolerance skills (BBDTS) measured by the 'Rotational Test' (RT) and time of
      transition (back and forth) on a 4 meter beam located 3 meters above the ground,
      was the criterion for simulation of a rescue task (SRT). RT and SRT were carried
      out first in a sports tracksuit and then in protective clothing. A total of 4
      results of the RT and SRT is the substantive base of the 4 rankings. The
      correlation of the RT and SRT results with 3 criteria for estimating BBDTS and 2
      categories ranged from 0.478 (p<0.01) - 0.884 (p<0.01) and the results of SRT
      0.911 (p<0.01). The basic ranking very highly correlated indicators of SRT (0.860
      and 0.844), while the 6 indicators of RT only 2 (0.396 and 0.381; p<0.05). There
      was no correlation between the results of the RT and SRT, but there was an
      important partial correlation of these variables, but only then was the effect
      stabilized. The Rotational Test is a simple and easy to use tool for measuring
      body balance disturbance tolerance skills. However, the BBDTS typology is an
      accurate criteria for forecasting on this basis, including the results of
      accurate motor simulations, and the periodic ability of firefighters to solve the
      most difficult rescue tasks.

PMID- 24738516
TI  - Effects of growth hormone and testosterone therapy on aerobic and anaerobic
      fitness, body composition and lipoprotein profile in middle-aged men.
AB  - INTRODUCTION: Andropause and aging are associated with neuroendocrine
      dysfunctions. Growth hormone and testosterone play a significant role in several
      processes affecting adaptation and thereby also everyday functioning. The aim of
      this research project was to evaluate the effects of recombinant human growth
      hormone and testosterone enanthate injections on body mass and body composition,
      aerobic and anaerobic fitness and lipid profile in middle-aged men. MATERIALS AND
      METHOD: The research group was comprised of 14 men aged 45 - 60 years. Two series
      of laboratory analyses were performed. Independent tests were carried out at
      baseline and after 12 weeks of the experiment. The data were analyzed using
      Statistica 9.1 software. RESULTS: A two-way repeated measures ANOVA revealed a
      statistically significant effect of the intervention programme on fat-free mass
      (eta(2)=0.34), total body fat (eta(2)=0.79), total cholesterol (eta(2)=0.30),
      high-density lipoprotein cholesterol (eta(2)=0.31), low-density lipoprotein
      cholesterol (eta(2)=0.42), triglyceride (eta(2)=0.28), testosterone
      (eta(2)=0.52), insulin-like growth factor 1 (eta(2)=0.47) and growth hormone
      (eta(2)=0.63). Furthermore, ANOVA revealed a statistically significant effect of
      the rhGH and T treatment on maximal oxygen uptake (eta(2)=0.63), anaerobic
      threshold (eta(2)=0.61) and maximal work rate (eta(2)=0.53). CONCLUSION: It
      should be emphasized that the lipid profile was affected not only by rhGH+T
      replacement therapy, but also by the prescribed physical activity programme. The
      strength and endurance fitness programme alone did not cause significant changes
      in body mass and composition, nor the anaerobic and aerobic capacity. On the
      other hand, the rhGH=T treatment stimulated these changes significantly.

PMID- 24738517
TI  - The influence of passive and active moral training on medical university on
      changes of students' moral competence index - results from randomized single
      blinded trial.
AB  - INTRODUCTION AND OBJECTIVES: Human's life as well as medical professions consist
      of many moral dilemmas. The aim of our study was to evaluate moral competences of
      midwifery students during their whole university education (3 year course) based
      on their moral competences C-index. MATERIAL AND METHOD: We performed randomized
      single blinded 3-year follow-up trial of 72 midwifery students. Standard Moral
      Judgment Test (MJT) By Georg Lind was used accompanied by own questionnaire.
      Moral competences were calculated (C-index) according to Lind's methodology.
      Subjects were also divided into active and passive ethics training to search for
      differences. RESULTS: C-index varied during studies insignificant (p=0.14).
      Randomized groups were equal at the beginning point, no significant differences
      were noticed. Active ethics teaching did not increase C-index compared to
      controls in all measuring points (P1-P4, respectively p=0,41 and p=0,38).
      CONCLUSIONS: During 3 year studies at medical university moral competences
      measured by C-index varied insignificantly, but simultaneously the change in C
      index was dependent on its value at the beginning of the trial. There was not
      statistically significant influence of active ethic's teaching compared to
      controls. Among social factors parents have strongest influence on students'
      morality, but growing role of Medical University in this hierarchy raises hopes
      for improvement in effectiveness of training in ethics.

PMID- 24738518
TI  - Telemedical systems for home monitoring of patients with chronic conditions in
      rural environment.
AB  - This paper describes the requirements and possible implementations of a
      telemedical system. The idea of remote patient monitoring is a point of interest
      for researchers in Poland, and is also in high demand in fields such as
      diabetology, cardiology, and geriatrics, among others. Aging society, medical
      care costs and many other factors make remote patient care a promising idea for
      the future. For each and every condition, a specialized type of sensor must be
      used to allow specific measurements to be performed. Moreover, a local data
      storage and communication device must be provided for the sensor to be able to
      relay data to the station. A smart phone can be used perform such tasks. By
      implementing such remote diagnostic systems it is possible to collect, process,
      store and present vital medical data that can be used immediately to perform
      diagnosis, or later as reference for expert systems. The 'Borboleta' and
      'SaguiSaude' systems already implemented can serve as a base for system analysis.
      The systems provide necessary functions and can be used as reference. Many
      factors contribute to the success of the telemedical system, such as ease of
      access, scalability, safety, platform independence, and many others. For easier
      implementation and clarity, the system should be divided into independent layers,
      which will also make it easier to modify and integrate into other medical
      systems. Making the system easy to use for patients, medical staff,
      administrators and data managers makes the task of system design especially
      challenging. One must decide which information is necessary for each type of user
      and provide them clearly and in an orderly fashion.

PMID- 24738519
TI  - Coupling forces resulting from the type of chain saw used.
AB  - INTRODUCTION: Woodcutters' working conditions are difficult due to the presence
      of numerous occupational hazards. Petrol-fuelled chain saws commonly used in
      forestry produce vibration, which may lead to the development of non-specific
      disorders in the upper extremities of the chain saw operator, referred to as hand
      arm vibration syndrome (HAVS). The magnitude of coupling forces exerted on a
      vibrating tool handle may affect the severity of HAVS and hand-wrist cumulative
      trauma disorders. The aim of the presented study was to measure coupling forces
      exerted by fellers on various chain saws and to find correlation between force
      magnitude and type of tool used. MATERIAL AND METHODS: Coupling forces applied by
      workers on different types of chain saws were measured by means of a hydro
      electronic force meter. All measurements were carried out during the harvesting
      of wood in real work conditions. RESULTS: Mean force applied by forestry workers
      on their tools was 44.2 N. Coupling forces registered during cutting wood with
      small universal chain saws were larger than forces exerted on models
      characterized by higher power profile. Forces applied on comparable tools
      produced by various manufacturers also differed. CONCLUSIONS: The relationship
      between coupling forces and power of the chain saw should lead to ergonomic
      improvements of the tool and vibration-reducing devices. These results can also
      be used as a recommendation for fellers in a range of using proper machines for
      different types of cut or types of wood. They may also be applicable to develop
      more effective methods for assessing vibration exposure risks among woodcutters.

PMID- 24738520
TI  - Postural stability disorders in rural patients with lumbar spinal stenosis.
AB  - INTRODUCTION: Hard work in farming may lead to lumbar spinal stenosis, and
      consequently, to pain. The pain and neurological disorders may lead to disability
      and postural disorders. OBJECTIVE: The aim of the presented study was to analyse
      postural stability and its correlation with functional disability of patients
      with lumbar spinal stenosis living in rural areas. MATERIALS AND METHODS: The
      study population consisted of 30 rural patients with lumbar spinal stenosis; mean
      age: 51.40 (+/-12.92); mean BMI: 28.60 (+/-3.77). The control group consisted of
      30 rural inhabitants without spinal disorders. Postural stability was tested on
      the Biodex Balance System. The patients were also evaluated according to the ODI,
      the Rolland- Morris disability questionnaire, and VAS. RESULTS: The mean results
      of the patients studied were as follows: 49.37 (+/-17.39) according to ODI, 15
      (+/-6.19) according to the Rolland-Morris disability scale, and pain intensity of
      7 (+/-1.93) according to the VAS. The following statistically significant
      differences were found: the mean balance index result was 1.8 (+/-1.88) and 0.64
      (+/-0.41) in the control group. The mean centre of mass deviation in the A/P
      plane was 1.39 (+/-1.88) and 0.46 (+/-0.41) in the control group. The mean centre
      of mass deviation in the M/L plane was 0.8 (+/-0.51) and 0.32 (+/-0.22) in the
      control group. The balance in the studied population correlated significantly
      with the Rolland-Morris disability questionnaire and the VAS. CONCLUSIONS: 1)
      Serious disability was found in rural patients with spinal stenosis. There was a
      statistically significant correlation between the disability and postural
      stability disorders. 2) Most of the patients (84%) were overweight. 3) Postural
      stability disorders were statistically significant for both the stability index
      and the A/P plane deviation.

PMID- 24738521
TI  - Narrative text analysis of accident reports with tractors, self-propelled
      harvesting machinery and materials handling machinery in Austrian agriculture
      from 2008 to 2010 - a comparison.
AB  - The aim of this study was the identification of accident scenarios and causes by
      analysing existing accident reports of recognized agricultural occupational
      accidents with tractors, self-propelled harvesting machinery and materials
      handling machinery from 2008 to 2010. As a result of a literature-based
      evaluation of past accident analyses, the narrative text analysis was chosen as
      an appropriate method. A narrative analysis of the text fields of accident
      reports that farmers used to report accidents to insurers was conducted to obtain
      detailed information about the scenarios and causes of accidents. This narrative
      analysis of reports was made the first time and yielded first insights for
      identifying antecedents of accidents and potential opportunities for technical
      based intervention. A literature and internet search was done to discuss and
      confirm the findings. The narrative text analysis showed that in more than one
      third of the accidents with tractors and materials handling machinery the vehicle
      rolled or tipped over. The most relevant accident scenarios with harvesting
      machinery were being trapped and falling down. The direct comparison of the
      analysed machinery categories showed that more than 10% of the accidents in each
      category were caused by technical faults, slippery or muddy terrain and incorrect
      or inappropriate operation of the vehicle. Accidents with tractors, harvesting
      machinery and materials handling machinery showed similarities in terms of
      causes, circumstances and consequences. Certain technical and communicative
      measures for accident prevention could be used for all three machinery
      categories. Nevertheless, some individual solutions for accident prevention,
      which suit each specific machine type, would be necessary.

PMID- 24738522
TI  - Stress, coping styles and personality tendencies of medical students of urban and
      rural origin.
AB  - INTRODUCTION: The problem of high levels of stress among medical students is a
      real problem and its prevalence and mechanisms have not yet been fully explored.
      It was found that there are only a few publications concerning the influence of
      urban and rural settings of the medical students in relation to stress, coping
      styles and personality tendencies. AIM: Analysis of the coping mechanisms and
      personality types of medical students of rural and urban origin based on the
      survey of the students of the Medical University in Lublin (MUL), south-east
      Poland. MATERIAL AND METHODS: The study was conducted with a group of 570 medical
      students from MUL, aged 19-35. Average medical student age: 22. Two
      questionnaires were used: CISS and SCID II for the evaluation of the coping
      styles and the personality tendency structures. RESULTS: The place of origin
      significantly influenced tendencies to the occurrence of specific personality
      types. The schizotypal, borderline and narcissistic personality tendencies mostly
      presented in big cities, less in small cities, and the least among students of
      rural origin. Dependent personality tendencies were significantly more common
      among females. The coping styles based on avoidance and on looking for the social
      contacts were significantly more common among females than males. CONCLUSIONS:
      Medical students of urban and rural origin were differentiated in terms of
      personality structure tendencies, concerning personalities: schizotypal,
      narcissistic and borderline. The tendencies to the dependent personality were
      also significantly more common among females than males. Two types of coping
      styles, based on avoidance and looking for social contacts, were significantly
      more common among females than males.

PMID- 24738523
TI  - Sexual activity of Polish adults.
AB  - AIM: The purpose of this research was to explore the subject of sexual activity
      in the Polish population, with special focus on age and gender differences, and
      sexual infidelity. Sexual activity is one of the basic factors in initiating and
      maintaining relationships. On the one hand, sexual activity enables us to meet
      natural needs and maintain an intimate relationship with another human being; on
      the other, it may allow us to overcome loneliness and social isolation by
      providing the opportunity to express feelings of closeness and unity. MATERIAL
      AND METHOD: The research was conducted on a representative group of 3,200 Poles
      aged between 15-49, with the support of a well-known Polish research company -
      TNS OBOP. Face-to-face and Pencil and Paper (PAPI) interviews were carried out.
      RESULTS: The results focus on two main issues: the age and motives of sexual
      initiation among teenagers (with a significant percentage starting their sexual
      activity at the age of 15), and the quality of the sexual lives of adults
      (average number of sexual partners, sexual infidelity and sexual satisfaction).
      CONCLUSION: There is dependence between the type of relationship and the
      performance or non-performance of sexual activity, as well as the quality of the
      relationship. Among both adolescents and adults, remaining in a stable
      relationship (partnership or marriage) promotes loyalty. The performance of
      sexual goals turns out to be an important mechanism regulating the interpersonal
      aspects of a relationship, influencing their perception and evaluation.

PMID- 24738524
TI  - Assessment of adequacy of vitamin D supplementation during pregnancy.
AB  - INTRODUCTION: Deficiency of vitamin D in pregnancy leads to higher incidences of
      preeclampsia, gestational diabetes, preterm birth, bacterial vaginosis, and also
      affects the health of the infants. According to Polish recommendations published
      in 2009, vitamin D supplementation in pregnant women should be provided from the
      2nd trimester of pregnancy in daily dose of 800-1000 IU. The aim of the presented
      study is: 1) to estimate how many pregnant women comply with those
      recommendations and 2) to determine the 25(OH)D levels in pregnant women.
      PATIENTS AND METHODS: The study included 88 pregnant women, aged 20-40 years,
      between 12-35 week of gestation. Vitamin D concentrations [25(OH)D] were measured
      by a direct electrochemiluminescence immunoassay (Elecsys, Roche). RESULTS: 31 of
      88 pregnant women (35.2%) did not use any supplementation. Mean level of 25(OH)D
      was 28.8 +/- 14.8 ng/mL (range from 4.0 - 77.5 ng/mL). Vitamin D deficiency,
      defined as 25(OH)D concentration below 20 ng/mL, was found in 31.8% of the women
      (28/88). Insufficiency of vitamin D [25(OH)D concentration between 20-30 ng/mL]
      was present in 26.1% of the women (23/88). Optimal level of 25(OH)D (over 30
      ng/mL) was present in 37/88 (42.0% women). Hence, in 46.2% of women taking
      vitamin D supplementation, the levels of 25(OH)D were still below 30 ng/mL.
      CONCLUSIONS: Supplementation of vitamin D in the investigated group was
      inadequate. More than 35% of pregnant women did not take any supplements, while
      half of the subjects who had declared taking vitamin D, failed to achieve optimal
      serum 25(OH)D concentration.

PMID- 24738525
TI  - Influence of calcium intake on bone mineral density and incidence of fractures in
      treatment-naive women from Lodz urban area - a part of EPOLOS study.
AB  - INTRODUCTION: Inadequate calcium intake is a recognized osteoporosis risk factor.
      The aim of the study was to estimate calcium intake in women in the Lodz
      population, the influence of calcium intake on bone mineral density (BMD) and
      fracture incidence, as well as the relationship between calcium intake and age.
      MATERIAL AND METHODS: This cross-sectional investigation is a part of the EPOLOS
      study (a multicentre, population-based study on osteoporosis risk factors in
      Poland). In this study, 277 women from the Lodz urban area were involved [aged 20
      80 years, not treated for osteoporosis before]. BMD was measured by dual-energy X
      ray absorptiometry (DXA) in the lumbar spine and femoral neck. Fractures were
      self-reported and calcium intake was calculated according to data gathered in a
      questionnaire. RESULTS: An average daily calcium intake was 797 +/- 432 mg. 65.7%
      of the examined women took less calcium than 1,000 mg/daily. Daily calcium intake
      decreased with age - from 903 mg between 20-30 years of age, to 624 mg between
      the ages of 70-80. In women aged 50 and older, the prevalence of low BMD at the
      lumbar spine (T-score <-1.0) was 31.9%. Patients reported 75 low-trauma
      fractures. There was a weak negative correlation between age and calcium intake,
      and no correlation between BMD and calcium intake. Women with fractures were
      significantly older than women without fractures, had significantly lower BMD,
      and similar levels of calcium intake. CONCLUSIONS: 1) Calcium intake below the
      recommended dietary intake was found in the majority of examined women. 2) No
      correlation between calcium intake and BMD, and between calcium intake and
      fracture incidence may suggest the involvement of factors other than calcium
      intake in pathogenesis of osteoporosis development. 3) Calcium intake gradually
      diminished with the age of the women.

PMID- 24738526
TI  - Emotional attitudes of young people completing secondary schools towards genetic
      modification of organisms (GMO) and genetically modified foods (GMF).
AB  - OBJECTIVE: The objective of the study was recognition of the opinions of
      adolescents completing secondary schools concerning genetically modified
      organisms and genetically modified food, especially the respondents' emotional
      attitude towards scientific achievements in the area of live genetically modified
      organisms. MATERIAL AND METHOD: The study covered a group of 500 school
      adolescents completing secondary school at the level of maturity examination. The
      study was conducted by the method of a diagnostic survey using a self-designed
      questionnaire form. RESULTS: Knowledge concerning the possible health effects of
      consumption of food containing GMO among adolescents competing secondary schools
      is on a relatively low level; the adolescents examined 'know rather little' or
      'very little know' about this problem. In respondents' opinions the results of
      reliable studies pertaining to the health effects of consumption of GMO 'rather
      do not exist'. The respondents are against the cultivation of GM plants and
      breeding of GM animals on own farm in the future. Secondary school adolescents
      considered that the production of genetically modified food means primarily the
      enrichment of biotechnological companies, higher income for food producers, and
      not the elimination of hunger in the world or elimination of many diseases
      haunting humans.

PMID- 24738527
TI  - Risk assessment of accidental exposure of surgeons to blood during orthopedic
      surgery. Are we safe in surgical gloves?
AB  - AIM: To analyze tears in sterile surgical gloves used by surgeons in the
      operating theatre of the Trauma and Orthopedic Surgery Department, Copernicus
      Memorial Hospital, Lodz, Poland. MATERIALS AND METHOD: This study analyzes tears
      in sterile surgical gloves used by surgeons by ICD-9 and ICD-10 codes. 1,404
      gloves were collected from 581 surgical procedures. All gloves were tested
      immediately following surgery using the test method described in Standard EN455-1
      (each glove was inflated with 1,000 +/- 50 ml of water and observed for leaks for
      2-3 min.). RESULTS: Analysis of tears took into consideration the role of medical
      personnel (operator, first assistant, second assistant) during surgical
      procedure, the type of procedure according to ICD-9 and ICD-10 codes, and the
      elective or emergency nature of the procedure. The results of the study show that
      these factors have a significant influence on the risk of glove tears.
      Significant differences were observed in tear frequency and tear location
      depending on the function performed by the surgeon during the procedure.
      CONCLUSION: The study proved that the role performed by the surgeon during the
      procedure (operator, first assistant, second assistant) has a significant
      influence on the risk of glove tearing. The role in the procedure determines
      exposure to glove tears. Implementing a double gloving procedure in surgical
      procedures or using single gloves characterized by higher tear resistance should
      be considered.

PMID- 24738528
TI  - The influence of upper airways diameter on the intensity of obstructive sleep
      apnea.
AB  - INTRODUCTION AND OBJECTIVE: Obstructive sleep apnea (OSA) is characterized by at
      least 5 ten-second-long episodes of apnea or hypopnea, per hour of sleep. This
      disease may lead to severe, life-threatening complications. Therefore, risk
      analysis and its influence on disease intensity is crucial for proper
      implementation of preventive treatments. OBJECTIVE: To determine the relation
      between the intensity of OSA expressed in Apnea-Hypopnea Index (AHI), and the
      anterior-posterior diameter of upper airways at the levels of soft palate and
      tongue base. MATERIAL AND METHOD: Medical records of 41 patients with sleep apnea
      (AHI>4) diagnosed through polysomnographic examination obstructive were used for
      the study. The data consisted of: age and gender, polysomnographic examination
      results (AHI), lateral cephalogram with cephalomertic analysis, together with
      measurements of the upper and lower pharyngeal depth according to McNamara.
      Statistical analysis was carried out in accordance with Pearson's r correlation
      coefficient test (Statistica 8.0 software package). RESULTS: Analysis of the
      influence of upper airways diameter on the intensity of OSA showed that the value
      of upper Airways diameter at the tongue base level had no statistically
      significant impact on the value of AHI (p=0.795). However, a statistically
      significant impact of the value of upper airways diameter on the AHI value
      (p=0.008) at the soft palate level was observed. Patients with OSA have narrowed
      upper airways diameter. The value of AHI increases with the decrease of upper
      diameter and is not dependent on a lower diameter value. Patients with a
      decreased upper airways diameter should be informed about potential breathing
      disorders during sleep.

PMID- 24738529
TI  - Connecting the dots: examining the link between workforce health and business
      performance.

PMID- 24738531
TI  - Trends in the financial burden of medical care for nonelderly adults with
      diabetes, 2001 to 2009.
AB  - OBJECTIVES: To examine trends in out-of-pocket spending and the financial burden
      of care for persons with diabetes between 2001 and 2009, and to examine whether
      these trends are consistent with trends in access to prescription drugs and
      utilization of hospital services. STUDY DESIGN AND METHODS: Data are from the
      2001 to 2009 Medical Expenditure Panel Survey (MEPS). The sample includes persons
      aged 18 to 64 years with diagnosed diabetes. The primary outcome variable is the
      percent of people with out-of-pocket spending on insurance premiums and services
      that exceed 10% of family income. Secondary outcome measures include the percent
      with diabetes-related prescription drug use, perceived access to prescription
      drugs, hospital inpatient stays, and emergency department use in the past 12
      months. Multiple regression analysis is used to control for changes in comorbid
      chronic conditions and other characteristics of persons with diabetes. RESULTS:
      Both out-of-pocket spending and the percent with high financial burden decreased
      markedly for persons with diabetes between 2001 to 2003 and 2007 to 2009. The
      decrease in spending was driven primarily by a decrease in spending on
      prescription drugs, including diabetes-related prescriptions. The shift from
      brand name drugs to generics accounts for much of this decline, although
      decreases in out-of-pocket spending for both brand name and generic drugs also
      contributed. During the same period, utilization of and access to diabetes
      related prescriptions increased, and hospital use decreased. CONCLUSIONS:
      Although the prevalence of diagnosed diabetes continues to increase, treatment is
      becoming more affordable, especially prescription drugs. This may offset some of
      the costs to the healthcare system of higher prevalence by reducing complications
      of uncontrolled diabetes that result in more costly hospital use.

PMID- 24738530
TI  - Physician financial incentives and care for the underserved in the United States.
AB  - OBJECTIVES: To estimate: (1) the percentage of physicians whose compensation is
      variable; (2) the frequency at which performance incentives for productivity,
      care quality, patient satisfaction, and resource use were used to determine
      compensation; and (3) how much incentives differ for physicians who serve greater
      percentages of patients who are Medicaid-insured, racial/ethnic minorities, or
      who face language barriers, versus those who do not. STUDY DESIGN: Cross
      sectional study of 3234 nationally representative physicians responding to the
      2008 Center for Studying Health System Change's Health Tracking Physician Survey
      (HTPS). METHODS: We examined the degree to which practices' percentage of
      Medicaid revenues and physicians' panel characteristics were associated with
      physicians' financial incentives using chi2 statistics and multivariate logistic
      regression (adjusting for physician specialty, practice type, and capitation
      levels, and area-based factors). RESULTS: Compensation was variable for 69% of
      respondents, was most frequently tied to productivity (68%), and less often to
      care quality (19%), patient satisfaction (21%), or resource use (14%). Physicians
      were significantly less likely to report variable compensation if the percentage
      Medicaid revenues was 50% or more (adjusted odds ratio [OR] 0.73, 95% confidence
      interval [CI], 0.57-0.95) or if physician panels were at least 50% Hispanic
      (adjusted OR 0.74, 95% CI, 0.56-0.99). However, physicians were significantly
      more likely to report use of all 4 performance incentives if percentage of
      Medicaid revenues was 6% to 24%. CONCLUSIONS: Physicians report different types
      of financial incentives designed to alter care quality and quantity; incentive
      types differ by the degree that practices derive revenues from Medicaid or serve
      Hispanic patients. Further investigation is needed to understand how to align
      financial incentives with disparity-reduction efforts.

PMID- 24738532
TI  - The impact of patient assistance programs and the 340B Drug Pricing Program on
      medication cost.
AB  - OBJECTIVES: Patient assistance programs and the 340B Drug Pricing Program promise
      to improve the financial stability, better serve vulnerable patients, and
      decrease the burden of cost for uninsured patients. Our objective is to examine
      the financial impact that PAPs and the 340B Program have on improving medication
      cost. STUDY DESIGN: Retrospective analysis of medication dispensary data.
      METHODS: Dispensary data for uninsured patients obtaining medications at 2
      community health centers were collected from February 1 to February 29, 2012.
      Uninsured patients were divided into 2 samples: (1) patients receiving PAP
      medications and (2) patients receiving 340B medications. The main outcome
      measured was the patient's cost savings. Cost savings were calculated based on
      the amount a medication would have cost had it been purchased by patients at
      prices found on Epocrates software (drugstore.com). A paired sample t test model
      using continuous variables was utilized to calculate confidence intervals.
      RESULTS: A total of 1420 PAP and 2772 340B individual medications were dispensed
      to uninsured patients in February 2012. For patients receiving PAP medications
      the mean +/- standard deviation (SD) for age = 52 +/- 10. Average cost was $0.11
      (95% CI, $0.04-$0.17) and average savings was $617.36 (95% Cl, $581.32-$653.40).
      For patients receiving 340B medications the mean +/-SD for age = 50 +/- 14.
      Average cost was $11.50 (95% CI, $10.55-$12.45). Average saving was $62.31 (95%
      CI, $57.99-$66.63). CONCLUSIONS: PAPs and 340B provide significant medication
      savings for uninsured patient. More research is needed to establish "best
      practices" for the successful integration of PAPs.

PMID- 24738533
TI  - Complying with state and federal regulations on essential drug benefits:
      implementing the Affordable Care Act.
AB  - OBJECTIVES: To examine health plan compliance with essential drug benefit
      regulations in California and Massachusetts and at the federal level. STUDY
      DESIGN: Health plan formulary review and analysis. METHODS: We analyzed
      formularies from the 3 largest small group plans in California and Massachusetts,
      including each state's benchmark plan. With respect to both federal and state
      regulations, for each health plan, we examined whether the drug was covered, the
      designated patient cost sharing tier of the drug, and which conditions of
      reimbursement were applied to the drug. RESULTS: Most drugs included in state and
      federal mandates are covered by both benchmark and non-benchmark plans. However,
      health plans are not fully compliant with state and federal regulations.
      Significant differences among plans relate more to cost sharing and conditions of
      reimbursement, such as prior authorization, step edits, and quantity limits, than
      to drug coverage. CONCLUSIONS/POLICY IMPLICATIONS: Because health plans in
      California and Massachusetts are not fully compliant with state and federal
      mandates, they will have to adjust their formularies to meet minimum
      requirements. State policy makers need to balance competing aims of
      comprehensiveness of coverage and drug affordability. They must consider: (1)
      choice of benchmark plan -choice of a more generous benchmark plan implies less
      leverage for negotiating lower prices; and (2) breadth of state mandates which,
      if they exceed federal mandates, must be paid for by the states.

PMID- 24738534
TI  - Patient attitudes about specialty follow-up care by telephone.

PMID- 24738535
TI  - Ability of different rescue therapies to save the bowel in acute, severe, steroid
      refractory ulcerative colitis.
AB  - To date, corticosteroids have been the primary therapies for acute, severe
      ulcerative colitis (UC). Patients not responding to intravenous steroids assessed
      at 3-5 days of the treatment are candidates for second-line rescue therapy.
      Cyclosporine (CsA), tacrolimus and infliximab (IFX) are also effective
      therapeutic options in acute, severe UC. In this review we summarized the results
      of the published studies examining and comparing the efficacy of CsA, tacrolimus
      and IFX as rescue therapies, and assessing the outcome of switching the drugs in
      case of therapeutic failure. 

PMID- 24738536
TI  - Cerebellum engages in automation of verb-generation skill.
AB  - Numerous studies have shown cerebellar involvement in item-specific association,
      a form of explicit learning. However, very few have demonstrated cerebellar
      participation in automation of non-motor cognitive tasks. Applying fMRI to a
      repeated verb-generation task, we sought to distinguish cerebellar involvement in
      learning of item-specific noun-verb association and automation of verb generation
      skill. The same set of nouns was repeated in six verb-generation blocks so that
      subjects practiced generating verbs for the nouns. The practice was followed by a
      novel block with a different set of nouns. The cerebellar vermis (IV/V) and the
      right cerebellar lobule VI showed decreased activation following practice;
      activation in the right cerebellar Crus I was significantly lower in the novel
      challenge than in the initial verb-generation task. Furthermore, activation in
      this region during well-practiced blocks strongly correlated with improvement of
      behavioral performance in both the well-practiced and the novel blocks,
      suggesting its role in the learning of general mental skills not specific to the
      practiced noun-verb pairs. Therefore, the cerebellum processes both explicit
      verbal associative learning and automation of cognitive tasks. Different
      cerebellar regions predominate in this processing: lobule VI during the
      acquisition of item-specific association, and Crus I during automation of verb
      generation skills through practice. 

PMID- 24738537
TI  - You know when: event-related potentials and theta/beta power indicate boundary
      prediction in music.
AB  - Neuroscientific and musicological approaches to music cognition indicate that
      listeners familiarized in the Western tonal tradition expect a musical phrase
      boundary at predictable time intervals. However, phrase boundary prediction
      processes in music remain untested. We analyzed event-related potentials (ERPs)
      and event-related induced power changes at the onset and offset of a boundary
      pause. We made comparisons with modified melodies, where the pause was omitted
      and filled by tones. The offset of the pause elicited a closure positive shift
      (CPS), indexing phrase boundary detection. The onset of the filling tones
      elicited significant increases in theta and beta powers. In addition, the P2
      component was larger when the filling tones started than when they ended. The
      responses to boundary omission suggest that listeners expected to hear a boundary
      pause. Therefore, boundary prediction seems to coexist with boundary detection in
      music segmentation. 

PMID- 24738538
TI  - Brain activity associated with translation from a visual to a symbolic
      representation in algebra and geometry.
AB  - This paper presents a small part of a larger interdisciplinary study that
      investigates brain activity (using event related potential methodology) of male
      adolescents when solving mathematical problems of different types. The study
      design links mathematics education research with neurocognitive studies. In this
      paper we performed a comparative analysis of brain activity associated with the
      translation from visual to symbolic representations of mathematical objects in
      algebra and geometry. Algebraic tasks require translation from graphical to
      symbolic representation of a function, whereas tasks in geometry require
      translation from a drawing of a geometric figure to a symbolic representation of
      its property. The findings demonstrate that electrical activity associated with
      the performance of geometrical tasks is stronger than that associated with
      solving algebraic tasks. Additionally, we found different scalp topography of the
      brain activity associated with algebraic and geometric tasks. Based on these
      results, we argue that problem solving in algebra and geometry is associated with
      different patterns of brain activity. 

PMID- 24738539
TI  - Brief neonatal handling alters sexually dimorphic behaviors in adult rats.
AB  - Several effects of neonatal handling on brain and behavior have been reported. We
      investigated the effects of neonatal handling on behaviors that have been shown
      to be sexually dimorphic in rats using an open-field test. "Gender differences"
      were observed in locomotor activity, exploratory behavior and grooming in the
      handled group. However, clear gender differences in these behaviors were not
      observed in the non-handled group. Our findings show that brief daily handling
      sessions (~ 1 min) in the first 2 weeks of postnatal life increased locomotor
      activity and exploratory behavior, and that these effects were more pronounced in
      females. Moreover, many rats in the non-handling group exhibited an increase in
      defecation relative to the handling group during the 10-min observation period.
      This suggests that the non-handling group experienced more stress in response to
      the novel open-field arena, and that this resulted in the absence of gender
      differences. Notably, this anxiety-related response was attenuated by neonatal
      handling. Our study underscores the impact of brief neonatal handling on sexually
      dimorphic behaviors, and indicates that caution should be exercised in
      controlling for the effects of handling between experimental groups, particularly
      in neurotoxicological studies that evaluate gender differences. 

PMID- 24738540
TI  - Influence of education level on design-induced N170 and P300 components of event
      related potentials in the human brain.
AB  - Simple geometric and organic shapes and their arrangement are being used in
      different neuropsychology tests for the assessment of cognitive function, special
      memory and also for the therapy purpose in different patient groups. Until now
      there is no electrophysiological evidence of cognitive function determination for
      simple geometric, organic shapes and their arrangement. Then the main objective
      of this study is to know the cortical processing and amplitude, latency of visual
      induced N170 and P300 event related potential components on different geometric,
      organic shapes and their arrangement and different educational influence on it,
      which is worthwhile to know for the early and better treatment for those patient
      groups. While education influenced on cognitive function by using auditory
      oddball task, little is known about the influence of education on cognitive
      function induced by visual attention task in case of the choice of geometric,
      organic shapes and their arrangements. Using a 128-electrode sensor net, we
      studied the responses of the choice of the different geometric and organic shapes
      randomly in experiment 1 and their arrangements in experiment 2 in the high,
      medium and low education groups. In both experiments, subjects push the button
      "1" or "2" if like or dislike, respectively. Total 45 healthy subjects (15 in
      each group) were recruited. ERPs were measured from 11 electrode sites and
      analyzed to see the evoked N170/N240 and P300 ERP components. There were no
      differences between like and dislike in amplitudes even in latencies in every
      stimulus in both experiments. We fixed geometric shapes and organic shapes
      stimuli only, not like and dislike. Upon the stimulus types, N170 ERP component
      was found instead of N240, in occipito-temporal (T5, T6, O1 and O2) locations
      where the amplitude is the highest at O2 location and P300 was distributed in the
      central (Cz and Pz) locations in both experiments in all groups. In experiment 1,
      significant low amplitude and non-significant larger latency of the N170
      component are found out at O1 location for both stimuli in low education group
      comparing medium education groups, but in experiment 2, there is no significant
      difference between stimuli among groups in amplitude and latency. In both
      experiments, P300 component was found in Cz and Pz locations though the
      amplitudes are higher at Cz than Pz areas. In experiment 1, medium education
      group evoked significantly (geometric shape stimuli, P = 0.05; organic shape
      stimuli, P = 0.02) higher amplitude of P300 component comparing low education
      group at Cz location. Whereas, there is no significant difference of amplitudes
      among groups across stimuli in Cz and Pz locations in experiment 2. Latencies
      have no significant differences in both experiments among groups also, but longer
      latency are found in low education group at Cz location comparing medium
      education group, though not significant. We conclude that simple geometric
      shapes, organic shapes and their arrangements evoked visual N170 component at
      temporo-occipital areas with right lateralization and P300 ERP component at
      centro-parietal areas. Significant low amplitude of N170 and P300 ERP components
      and longer latencies during different shape stimuli in low education group prove
      that, low education significantly influence on visual cognitive functions in low
      education group. 

PMID- 24738541
TI  - Emotion classification in Parkinson's disease by higher-order spectra and power
      spectrum features using EEG signals: a comparative study.
AB  - Deficits in the ability to process emotions characterize several neuropsychiatric
      disorders and are traits of Parkinson's disease (PD), and there is need for a
      method of quantifying emotion, which is currently performed by clinical
      diagnosis. Electroencephalogram (EEG) signals, being an activity of central
      nervous system (CNS), can reflect the underlying true emotional state of a
      person. This study applied machine-learning algorithms to categorize EEG
      emotional states in PD patients that would classify six basic emotions (happiness
      and sadness, fear, anger, surprise and disgust) in comparison with healthy
      controls (HC). Emotional EEG data were recorded from 20 PD patients and 20
      healthy age-, education level- and sex-matched controls using multimodal (audio
      visual) stimuli. The use of nonlinear features motivated by the higher-order
      spectra (HOS) has been reported to be a promising approach to classify the
      emotional states. In this work, we made the comparative study of the performance
      of k-nearest neighbor (kNN) and support vector machine (SVM) classifiers using
      the features derived from HOS and from the power spectrum. Analysis of variance
      (ANOVA) showed that power spectrum and HOS based features were statistically
      significant among the six emotional states (p < 0.0001). Classification results
      shows that using the selected HOS based features instead of power spectrum based
      features provided comparatively better accuracy for all the six classes with an
      overall accuracy of 70.10% +/- 2.83% and 77.29% +/- 1.73% for PD patients and HC
      in beta (13-30 Hz) band using SVM classifier. Besides, PD patients achieved less
      accuracy in the processing of negative emotions (sadness, fear, anger and
      disgust) than in processing of positive emotions (happiness, surprise) compared
      with HC. These results demonstrate the effectiveness of applying machine learning
      techniques to the classification of emotional states in PD patients in a user
      independent manner using EEG signals. The accuracy of the system can be improved
      by investigating the other HOS based features. This study might lead to a
      practical system for noninvasive assessment of the emotional impairments
      associated with neurological disorders. 

PMID- 24738542
TI  - Physiological effects of mechanical pain stimulation at the lower back measured
      by functional near-infrared spectroscopy and capnography.
AB  - The aim was to investigate the effect of mechanical pain stimulation at the lower
      back on hemodynamic and oxygenation changes in the prefrontal cortex (PFC)
      assessed by functional near-infrared spectroscopy (fNIRS) and on the partial
      pressure of end-tidal carbon dioxide ( PetCO 2) measured by capnography. 13
      healthy subjects underwent three measurements (M) during pain stimulation using
      pressure pain threshold (PPT) at three locations, i.e., the processus spinosus at
      the level of L4 (M1) and the lumbar paravertebral muscles at the level of L1 on
      the left (M2) and the right (M3) side. Results showed that only in the M2
      condition the pain stimulation elicited characteristic patterns consisting of (1)
      a fNIRS-derived decrease in oxy- and total hemoglobin concentration and tissue
      oxygen saturation, an increase in deoxy-hemoglobin concentration, (2) a decrease
      in the PetCO 2 response and (3) a decrease in coherence between fNIRS parameters
      and PetCO 2 responses in the respiratory frequency band (0.2-0.5 Hz). We discuss
      the comparison between M2 vs. M1 and M3, suggesting that the non-significant
      findings in the two latter measurements were most likely subject to effects of
      the different stimulated tissues, the stimulated locations and the stimulation
      order. We highlight that PetCO 2 is a crucial parameter for proper interpretation
      of fNIRS data in experimental protocols involving pain stimulation. Together, our
      data suggest that the combined fNIRS-capnography approach has potential for
      further development as pain monitoring method, such as for evaluating clinical
      pain treatment. 

PMID- 24738543
TI  - Integration of memory, perception and attention in episode processing.
AB  - The goal of this paper is to examine abstract, non-neuronal level concepts and
      processes of cognition and to introduce a model of episode processing which
      includes processing of perception and memory for ordered events, attentional
      processes, forgetting (including both constant and non-constant time-based
      decay), confusions and distinctiveness between items, and false memories and
      their suppression. 

PMID- 24738545
TI  - Inter-rater reliability of a food store checklist to assess availability of
      healthier alternatives to the energy-dense snacks and beverages commonly consumed
      by children.
AB  - BACKGROUND: Food stores have gained attention as potential intervention targets
      for improving children's eating habits. There is a need for valid and reliable
      instruments to evaluate changes in food store snack and beverage availability
      secondary to intervention. The aim of this study was to develop a valid,
      reliable, and resource-efficient instrument to evaluate the healthfulness of food
      store environments faced by children. METHODS: The SNACZ food store checklist was
      developed to assess availability of healthier alternatives to the energy-dense
      snacks and beverages commonly consumed by children. After pretesting, two trained
      observers independently assessed the availability of 48 snack and beverage items
      in 50 food stores located near elementary and middle schools in Portland, Oregon,
      over a 2-week period in summer 2012. Inter-rater reliability was calculated using
      the kappa statistic. RESULTS: Overall, the instrument had mostly high inter-rater
      reliability. Seventy-three percent of items assessed had almost perfect or
      substantial reliability. Two items had moderate reliability (0.41-0.60), and no
      items had a reliability score less than 0.41. Eleven items occurred too
      infrequently to generate a kappa score. CONCLUSION: The SNACZ food store
      checklist is a first-step toward developing a valid and reliable tool to evaluate
      the healthfulness of food store environments faced by children. The tool can be
      used to compare availability of healthier snack and beverage alternatives across
      communities and measure change secondary to intervention. As a wider variety of
      healthier snack and beverage alternatives become available in food stores, the
      checklist should be updated.

PMID- 24738548
TI  - Overlapping verbal, relational, physical, and electronic forms of bullying in
      adolescence: influence of school context.
AB  - Interest in youths' experience of the various forms of bullying has grown due to
      the numerous social-emotional correlates associated with bullying. Only recently
      has there been consideration of the school context in light of these
      associations. The current study examined the overlap in four different forms of
      bullying that youth commonly experience (i.e., verbal, relational, physical,
      electronic), with the aim of understanding their association with social
      emotional correlates (i.e., internalizing symptoms, externalizing symptoms,
      retaliatory attitudes) and exploring associations with school contextual factors
      such as supervision, school physical disorder, and behavioral expectations. Self
      report data on the forms of peer bullying were collected from 24,620 adolescents
      (Grades 9-12; M age = 15.98, SD age = 1.32) enrolled in 52 high schools. Latent
      class analyses indicated significant overlap in the different forms of bullying
      victimization, with youth experiencing multiple forms of bullying reporting the
      greatest risk for social-emotional problems. A series of two-level hierarchical
      linear models revealed that indicators of school physical disorder and a lack of
      positive behavioral expectations were associated with increased risk for multiple
      forms of bullying. Several gender and age differences were also observed in
      relation to the patterns of bullying experienced. These findings extend prior
      research by emphasizing a potential link between the overlap in different forms
      of bullying and school contextual factors, even after controlling for individual
      level risk factors. 

PMID- 24738549
TI  - Structural insight into the binding interactions of modeled structure of
      Arabidopsis thaliana urease with urea: an in silico study.
AB  - Urease (EC 3.5.1.5., urea amidohydrolase) catalyzes the hydrolysis of urea to
      ammonia and carbon dioxide. Urease is present to a greater abundance in plants
      and plays significant role related to nitrogen recycling from urea. But little is
      known about the structure and function of the urease derived from the Arabidopsis
      thaliana, the model system of choice for research in plant biology. In this
      study, a three-dimensional structural model of A. thaliana urease was constructed
      using computer-aided molecular modeling technique. The characteristic structural
      features of the modeled structure were then studied using atomistic molecular
      dynamics simulation. It was observed that the modeled structure was stable and
      regions between residues index (50-80, 500-700) to be significantly flexible.
      From the docking studies, we detected the possible binding interactions of
      modeled urease with urea. Ala399, Ile675, Thr398, and Thr679 residues of A.
      thaliana urease were observed to be significantly involved in binding with the
      substrate urea. We also compared the docking studies of ureases from other
      sources such as Canavalia ensiformis, Helicobacter pylori, and Bacillus
      pasteurii. In addition, we carried out mutation analysis to find the highly
      mutable amino acid residues of modeled A. thaliana urease. In this particular
      study, we observed Met485, Tyr510, Ser786, Val426, and Lys765 to be highly
      mutable amino acids. These results are significant for the mutagenesis analysis.
      As a whole, this study expounds the salient structural features as well the
      binding interactions of the modeled structure of A. thaliana urease. 

PMID- 24738550
TI  - Virtual patient simulations and optimal social learning context: a replication of
      an aptitude-treatment interaction effect.
AB  - BACKGROUND: Virtual patients (VPs) offer valuable alternative encounters when
      live patients with rare conditions, such as cranial nerve (CN) palsies, are
      unavailable; however, little is known regarding simulation and optimal social
      learning context. AIM: Compare learning outcomes and perspectives between
      students interacting with VPs in individual and team contexts. METHODS: Seventy
      eight medical students were randomly assigned to interview and examine four VPs
      with possible CN damage either as individuals or in three-person teams, using
      Neurological Examination Rehearsal Virtual Environment (NERVE). Learning was
      measured through diagnosis accuracy and pre-/post-simulation knowledge scores.
      Perspectives of learning context were collected post-simulation. RESULTS:
      Students in teams submitted correct diagnoses significantly more often than
      students as individuals for CN-IV (p = 0.04; team = 86.1%; individual = 65.9%)
      and CN-VI (p = 0.03; team = 97.2%; individual = 80.5%). Knowledge scores
      increased significantly in both contexts (p < 0.001); however, a significant
      aptitude-treatment interaction effect was observed (p = 0.04). At pre-test scores
      <=25.8%, students in teams scored significantly higher (66.7%) than students as
      individuals (43.1%) at post-test (p = 0.03). Students recommended implementing
      future NERVE exercises in teams over five other modality-timing combinations.
      CONCLUSION: Results allow us to define best practices for integrating VP
      simulators into medical education. Implementing NERVE experiences in team
      environments with medical students in the future may be preferable.

PMID- 24738551
TI  - Parenteral patent drug S/GSK1265744 has the potential to be an effective agent in
      pre-exposure prophylaxis against HIV infection.
AB  - The continuing HIV epidemic has driven advancements in antiretroviral therapy.
      New therapeutic targets have been identified over the past years, one of which
      has been the Integrase enzyme. This is responsible for integrating HIV pro-DNA
      into the host cell genome and has proved a successful drug target. Efforts have
      also been made to improve the pharmacokinetic parameters of current drug therapy
      and utilise these techniques in maximising drug therapeutic effect whilst
      minimising adverse events. An exciting example of new technologies is that of
      nanotechnology where drugs can be specifically targeted to certain tissues and
      drug delivery can be improved by utilising biological molecules and structures.
      Pre-exposure prophylaxis is also an area of much interest currently both on an
      individual and population level. Compliance is however a major issue with daily
      medication to prevent HIV acquisition as has been demonstrated with contraceptive
      agents. However if long acting compounds can be developed, compliance can be
      improved. The patent drug currently being developed through nanotechnology as an
      analogue of Dolutegravir, GSK1265744 LAP (Long Acting Parenteral) has shown
      promise as a Long Acting Integrase Inhibitor with potential action both as a
      therapeutic agent but also in pre-exposure prophylaxis. The favourable
      pharmacokinetic profile and therapeutic efficacy in comparison to other compounds
      of the same class demonstrate it to be a promising advance. However given current
      limitations in study material, further randomised studies with long term follow
      up are required to fully evaluate the value of the patent drug GSK1265744 LAP in
      action in both seropositive and seronegative individuals. 

PMID- 24738552
TI  - Positive predictive values of ICD-9 codes to identify patients with stroke or
      TIA.
AB  - OBJECTIVES: To determine the positive predictive values of inpatient and
      outpatient ICD-9 codes and status code V12.54 for identifying confirmed history
      of stroke or transient ischemic attack (cerebral event) among patients within a
      managed care organization. STUDY DESIGN: Retrospective, cohort study. METHODS:
      Inpatient hospital claims and outpatient visit records were used to identify
      patients with ICD-9 codes (430.XX to 438.XX) or status code V12.54 in the primary
      or secondary position recorded between January 1, 2001, and December 31, 2009. A
      standardized chart abstraction tool was used by trained chart abstractors blinded
      to the coding to confirm the cerebral event and classify stroke type. Positive
      predictive values (PPVs) were calculated for each code based on care setting.
      RESULTS: A total of 4689 patients with 10,376 unique stroke codes recorded in the
      administrative data were reviewed. Of these, 2785 (59.4%) patients had a
      confirmed cerebral event. The codes with PPV less than 90% were 434.XX, 433 .X1,
      and V12.54 where codes were recorded in both the inpatient and outpatient
      settings. Overall, inpatient-only codes produced higher PPVs; however, relatively
      fewer events were captured in this setting. CONCLUSIONS: Administrative ICD-9
      codes 434.XX, 433.X1, and V12.54 had consistently high PPVs in identifying
      patients with a confirmed cerebral event. These codes could be used as part of a
      probabilistic approach to focus care activities on patients with the highest
      likelihood of a cerebral event.

PMID- 24738553
TI  - Dialing in: effect of telephonic wellness coaching on weight loss.
AB  - OBJECTIVE: To estimate the effect of telephonic wellness coaching on weight loss
      in a commercially insured population. STUDY DESIGN: Pre-post evaluation design.
      METHODS: Self-reported weight was obtained from 2 annual health assessment
      questionnaires administered during 2008 and 2010. Baseline (T1) information from
      these questionnaires was used to identify overweight/obese individuals and to
      determine targets for a 4-call wellness coaching program. Overweight/obese
      individuals identified at T1 were classified into following groups: (1) targeted
      for wellness coaching (N = 1448, including 1050 participants and 398
      nonparticipants); (2) not targeted for wellness coaching, but targeted for other
      telephonic wellness care management (WCM) programs (N = 1270); (3) not targeted
      for any WCM programs (N = 7586). Weight reported on questionnaires a year later
      (T2) was used to calculate weight change between T1 and T2. Paired t-tests were
      used to detect significant weight changes over time. Multivariable linear
      regressions were used to compare weight changes between the groups. Stratified
      analysis was conducted to determine the effectiveness of telephonic wellness
      coaching for subgroups based on participants' selected health goals, intensity of
      the intervention received and initial stage of change. RESULTS: The group
      targeted for wellness coaching reported an average weight change of -0.44 kg (95%
      confidence interval [CI], -0.76 to -0.16) at T2, significantly more weight loss
      than reported by the group not targeted for any WCM programs. Participants who
      started in preparation stage and completed the program reported weight change of 
      1.43 kg (95% CI, -2.17 to -0.68), highest among program participants.
      CONCLUSIONS: Small weight loss was observed for obese/individuals targeted for
      telephonic wellness coaching.

PMID- 24738555
TI  - Formulary restrictions on atypical antipsychotics: impact on costs for patients
      with schizophrenia and bipolar disorder in Medicaid.
AB  - OBJECTIVES: To measure the impact of state Medicaid formulary policies on costs
      for patients with schizophrenia and bipolar disorder. STUDY DESIGN: Retrospective
      analysis of medical and pharmacy claims for patients diagnosed with schizophrenia
      or bipolar disorder in 24 state Medicaid programs. METHODS: We combined
      information on formulary restrictions in Medicaid with the medical and pharmacy
      claims of 117,908 patients with schizophrenia and 170,596 patients with bipolar
      disorder in Medicaid who were single-eligible, and newly prescribed a second
      generation antipsychotic from 2001 to 2008. We tested the impact of formulary
      restrictions on the medical costs and utilization of patients in the 12 months
      after the index prescription. To capture social costs in addition to medical
      expenditures in Medicaid, we estimated the incremental costs of incarcerating
      patients with schizophrenia and bipolar disorder associated with formulary
      restrictions. RESULTS: Patients with schizophrenia subject to formulary
      restrictions were more likely to be hospitalized (odds ratio 1.13, P <.001), had
      23% higher inpatient costs (P <.001), and 16% higher total costs (P <.001).
      Similar effects were observed for patients with bipolar disorder. Our estimates
      suggest restrictive formulary policies in Medicaid increased the number of
      prisoners by 9920 and incarceration costs by $362 million nationwide in 2008.
      CONCLUSIONS: Applying formulary restrictions to atypical antipsychotics is
      associated with higher total medical expenditures for patients with schizophrenia
      and bipolar disorder in Medicaid. Combined with the other social costs such as an
      increase in incarceration rates, these formulary restrictions could increase
      state costs by $1 billion annually, enough to offset any savings in pharmacy
      costs.

PMID- 24738554
TI  - Impact of a Medicare MTM program: evaluating clinical and economic outcomes.
AB  - OBJECTIVES: To assess the impact of a Medicare Medication Therapy Management
      (MTM) program in a large integrated health plan on patient mortality,
      hospitalization and emergency department (ED) utilization, and daily prescription
      costs. STUDY DESIGN: Retrospective matched cohort study. METHODS: Patients who
      received MTM services between 2006 and 2010 were matched to control patients who
      were enrolled in Medicare but did not receive MTM services. They were matched in
      a 1:4 ratio based on age, gender, geographic location, and prospective diagnostic
      cost-group (DxCG) risk score. Multivariate regressions were used to analyze the
      outcomes. Subgroup analyses were conducted for patients enrolled in 2010 because
      the Centers for Medicare & Medicaid Services lowered the drug-cost threshold for
      MTM eligibility and changed from opt-in to optout participation. RESULTS: We
      identified 34,532 members who received MTM services and 138,128 control members.
      The MTM group was found to have a significantly reduced mortality (hazard ratio
      0.86, 95% confidence interval [CI], 0.84-0.88; P <.001), lower odds for
      hospitalization (odds ratio [OR] = 0.97, 95% CI, 0.94-0.99; P = .018), higher
      odds for emergency department visits (OR = 1.17, 95% CI, 1.14-1.20; P <.001), and
      no differences in change in daily medication costs when compared to the matched
      group. The subgroup analysis of the 2010 cohort found similar results with better
      outcomes than the overall cohort. CONCLUSIONS: Medicare MTM services resulted in
      lower mortality and odds for hospitalization for enrolled patients compared with
      matched controls. This study observed an increase in ED visits and no differences
      in change in daily medication costs in MTM services.

PMID- 24738556
TI  - The role of magical thinking in hallucinations. Comparisons of clinical and non
      clinical groups.
AB  - BACKGROUND: Magical thinking consists of accepting the possibility that events
      that, according to the causal concepts of a culture, cannot have any causal
      relationship, but might somehow nevertheless have one. Magical thinking has been
      related to both obsessive-compulsive disorder and schizophrenia. AIMS: The
      purpose of this study was to investigate the role of magical thinking in
      hallucinations of patients diagnosed with schizophrenia. METHODS: Four groups
      were recruited for this purpose from a clinical population (hallucinating
      schizophrenic patients, patients diagnosed with psychoses who had never
      hallucinated, obsessive-compulsive disorder patients and a clinical control
      group) and a non-clinical control group, who were given the Magical Ideation
      Scale. RESULTS: The results show that magical ideation differentiates the group
      of schizophrenic patients with auditory hallucinations from the rest of the
      groups that participated in the design. Items related to "mind reading", to the
      presence of auditory illusions in response to sound stimuli, and to the sense of
      sometimes being accompanied by an evil presence are the most closely related to
      the presence of auditory hallucinations. CONCLUSIONS: Magical thinking,
      understood as beliefs in non-consensual modes of causation, is closely linked to
      auditory hallucinations in patients diagnosed with schizophrenia.

PMID- 24738558
TI  - Dissecting the structure of thiopeptides: assessment of thiazoline and tail
      moieties of baringolin and antibacterial activity optimization.
AB  - Several analogues of baringolin (1) were prepared to evaluate the role of its
      characteristic thiazoline ring and pentapeptidic tail with the aim of defining
      structure-activity relationships for these moieties. The thiazoline ring appeared
      as a crucial moiety to maintain a broad scope of activities against different
      Gram-positive bacteria. Further modifications were performed to simplify the
      structure of the natural product and assess the role of its tail, resulting in an
      enhanced in vitro performance. Analogue 25, with the thiazole-containing
      macrocycle and a 4-aminocyclohexane-1-carboxylic acid moiety in place of the
      pentapeptidic tail, was identified as a much more potent analogue, capable of
      overcoming the absence of the thiazoline ring and performing extraordinarily well
      against all strains tested. This is the first library of thiopeptide analogues
      produced by chemical synthesis alone, which demonstrates the robustness and
      convenience of the synthetic strategy used. 

PMID- 24738559
TI  - Lipid dynamics studied by calculation of 31P solid-state NMR spectra using
      ensembles from molecular dynamics simulations.
AB  - We present a method to calculate (31)P solid-state NMR spectra based on the
      dynamic input from extended molecular dynamics (MD) simulations. The dynamic
      information confered by MD simulations is much more comprehensive than the
      information provided by traditional NMR dynamics models based on, for example,
      order parameters. Therefore, valuable insight into the dynamics of biomolecules
      may be achieved by the present method. We have applied this method to study the
      dynamics of lipid bilayers containing the antimicrobial peptide alamethicin, and
      we show that the calculated (31)P spectra obtained with input from MD simulations
      are in agreement with experiments under a large range of different sample
      conditions, including vesicles and oriented samples with and without peptides. We
      find that the changes in the (31)P spectra upon addition of peptide stem from
      lipids with reduced diffusion due to peptide-lipid interactions. 

PMID- 24738557
TI  - Lithium and autophagy.
AB  - Lithium, a drug used to treat bipolar disorders, has a variety of neuroprotective
      mechanisms, including autophagy regulation, in various neuropsychiatric
      conditions. In neurodegenerative diseases, lithium enhances degradation of
      aggregate-prone proteins, including mutated huntingtin, phosphorylated tau, and
      alpha-synuclein, and causes damaged mitochondria to degrade, while in a mouse
      model of cerebral ischemia and Alzheimer's disease autophagy downregulation by
      lithium is observed. The signaling pathway of lithium as an autophagy enhancer
      might be associated with the mammalian target of rapamycin (mTOR)-independent
      pathway, which is involved in myo-inositol-1,4,5-trisphosphate (IP3) in
      Huntington's disease and Parkinson's disease. However, the mTOR-dependent pathway
      might be involved in inhibiting glycogen synthase kinase-3beta (GSK3beta) in
      other diseases. Lithium's autophagy-enhancing property may contribute to the
      therapeutic benefit of patients with neuropsychiatric disorders.

PMID- 24738561
TI  - Collective goals and shared tasks: interdependence structure and perceptions of
      individual sport team environments.
AB  - Across two studies, we tested the proposition that interdependence structures
      (i.e., task interaction among teammates during competition, competition against
      teammates, presence of a collective outcome) influence interdependence
      perceptions among teammates as well as perceptions of group cohesion,
      competitiveness, and satisfaction. Study 1 was a paper-and-pencil survey
      completed by 210 individual sport athletes from 12 university- and college-level
      teams. Multiple mediation analyses demonstrated that participants who had to work
      alongside teammates during competition reported increased interdependence
      perceptions that were, in turn, associated with increased cohesion and
      satisfaction as well as decreased competitiveness. There were no differences
      according to whether participants competed in the same event as all of their
      teammates or not. Study 2 involved a weekly e-mail survey with 17 university
      level individual sport athletes who reported interdependence perceptions on a
      continual basis over the course of their competitive season. Interdependence
      perceptions were higher during weeks that were close in time to competitions with
      a collective group outcome. These studies reveal how interdependence structures
      shape the group environment and support applied efforts that consider ways to
      structure teammate interdependencies in ways to optimize group functioning and
      promote member satisfaction.

PMID- 24738560
TI  - Roles of long-range tertiary interactions in limiting dynamics of the Tetrahymena
      group I ribozyme.
AB  - We determined the effects of mutating the long-range tertiary contacts of the
      Tetrahymena group I ribozyme on the dynamics of its substrate helix (referred to
      as P1) and on catalytic activity. Dynamics were assayed by fluorescence
      anisotropy of the fluorescent base analogue, 6-methyl isoxanthopterin,
      incorporated into the P1 helix, and fluorescence anisotropy and catalytic
      activity were measured for wild type and mutant ribozymes over a range of
      conditions. Remarkably, catalytic activity correlated with P1 anisotropy over 5
      orders of magnitude of activity, with a correlation coefficient of 0.94. The
      functional and dynamic effects from simultaneous mutation of the two long-range
      contacts that weaken P1 docking are cumulative and, based on this RNA's topology,
      suggest distinct underlying origins for the mutant effects. Tests of mechanistic
      predictions via single molecule FRET measurements of rate constants for P1
      docking and undocking suggest that ablation of the P14 tertiary interaction frees
      P2 and thereby enhances the conformational space explored by the undocked
      attached P1 helix. In contrast, mutation of the metal core tertiary interaction
      disrupts the conserved core into which the P1 helix docks. Thus, despite
      following a single correlation, the two long-range tertiary contacts facilitate
      P1 helix docking by distinct mechanisms. These results also demonstrate that a
      fluorescence anisotropy probe incorporated into a specific helix within a larger
      RNA can report on changes in local helical motions as well as differences in more
      global dynamics. This ability will help uncover the physical properties and
      behaviors that underlie the function of RNAs and RNA/protein complexes. 

PMID- 24738562
TI  - A mixed-ligand approach for spin-crossover modulation in a linear Fe(II)
      coordination polymer.
AB  - In this work, we present a family of Fe(II) coordination polymers of general
      formula [Fe(btzx)(3-3x)(btix)(3x)](ClO4)2 with interesting spin-crossover
      properties. These coordination polymers have been synthesized using chemical
      mixtures of two different but closely related ligands, 1,4-bis(tetrazol-1
      ylmethyl)benzene (btzx) and 1,4-bis(triazol-1-ylmethyl)benzene (btix), and the
      effect of a gradual substitution of the ligand in the spin transition temperature
      has been investigated. Several chemical mixtures have been structurally
      characterized by X-ray powder diffraction indicating a clear critical amount in
      the composition of the mixture after which mixed phases rather than a single
      phase comprising mixed components are observed. Importantly, this approach causes
      the appearance of a new transition at lower temperatures that is not present in
      the pure [Fe(L)3](ClO4)2 systems.

PMID- 24738563
TI  - Evidence for acute central sensitization to prolonged experimental pain in
      posttraumatic stress disorder.
AB  - BACKGROUND: Post-traumatic stress disorder (PTSD) and pain have a well-documented
      high comorbidity; however, the underlying mechanisms of this comorbidity are
      currently poorly understood. The aim of this psychophysical study was to
      investigate the behavioral response to a prolonged suprathreshold pain stimulus
      in subjects with combat-related PTSD and combat controls (CC) for clinical
      evidence of central sensitization. METHODS: Ten male subjects with current PTSD
      related to combat and 11 CC male subjects underwent baseline quantitative sensory
      testing (QST), temporal pain summation, and psychological profiling followed by
      an intramuscular injection of capsaicin into the quadriceps muscle. RESULTS:
      There was no significant between-group difference for the initial maximal pain
      response or an initial pain reduction for the first 15 minutes postinjection on
      QST or pain ratings. However, we observed significantly higher scores in the PTSD
      group for the second 15 minutes postinjection on both pain intensity and pain
      unpleasantness ratings. Assessment of temporal summation to repetitive pressure
      stimuli showed significantly higher subjective pain in the PTSD group.
      CONCLUSION: These findings are consistent with a significantly higher degree of
      acute central sensitization in individuals with PTSD. Increased acute central
      sensitization may underlie increased vulnerability for developing pain-related
      conditions following combat trauma.

PMID- 24738568
TI  - Breast involvement by schistosomiasis.

PMID- 24738569
TI  - Focal epithelial hyperplasia associated with human papillomavirus 13 and common
      human leukocyte antigen alleles in a Turkish family.
AB  - BACKGROUND: Focal epithelial hyperplasia (FEH) is a rare and benign papillomatous
      disease of the oral cavity, which is closely associated with human papillomavirus
      (HPV) type 13 and 32. Genetic susceptibility to HPV infections are supported by
      recent studies involving the human leukocyte antigen system (HLA). In this
      report, we aimed to determine the clinicopathological features of a Turkish
      family with FEH and to detect the shared HLA DR and DQ types. METHODS: HPV DNA
      typing of tissue samples and HLA determination from blood samples of four family
      members were performed by polymerase chain reaction. RESULTS: Histopathological
      examination of all patients revealed acanthotic papillomatous epidermis,
      koilocytes, apoptotic keratinocytes, and mitosoid bodies. HPV13 was detected by
      polymerase chain reaction. HLA DQA1*0501, HLA DQB1*0302, and HLA DRB1*11 alleles
      were common in all family members. HLA DRB1*04 was detected in three of them.
      CONCLUSION: This report is the first step for the investigation of involvement of
      HLA types in the pathogenesis of Turkish patients with FEH.

PMID- 24738564
TI  - Design and applications of bispecific heterodimers: molecular imaging and beyond.
AB  - Ligand-based molecular imaging probes have been designed with high affinity and
      specificity for monitoring biological process and responses. Single-target
      recognition by traditional probes can limit their applicability for disease
      detection and therapy because synergistic action between disease mediators and
      different receptors is often involved in disease progression. Consequently,
      probes that can recognize multiple targets should demonstrate higher targeting
      efficacy and specificity than their monospecific peers. This concept has been
      validated by multiple bispecific heterodimer-based imaging probes that have
      demonstrated promising results in several animal models. This review summarizes
      the design strategies for bispecific peptide- and antibody-based heterodimers and
      their applications in molecular targeting and imaging. The design and application
      of bispecific heterodimer-conjugated nanomaterials are also discussed.

PMID- 24738570
TI  - A study of the eigenvectors of the vibrational modes in crystalline cytidine via
      high-pressure Raman spectroscopy.
AB  - Raman spectroscopy has been used to study the eigenvectors and eigenvalues of the
      vibrational modes of crystalline cytidine at 295 K and high pressures by
      evaluating the logarithmic derivative of the vibrational frequency omega with
      respect to pressure P: [Formula: see text]. Crystalline samples of molecular
      materials have strong intramolecular bonds and weak intermolecular bonds. This
      hierarchy of bonding strengths causes the vibrational optical modes localized
      within a molecular unit ("internal" modes) to be relatively high in frequency
      while the modes in which the molecular units vibrate against each other
      ("external" modes) have relatively low frequencies. The value of the logarithmic
      derivative is a useful diagnostic probe of the nature of the eigenvector of the
      vibrational modes because stretching modes (which are predominantly internal to
      the molecule) have low logarithmic derivatives while external modes have higher
      logarithmic derivatives. In crystalline cytidine, the modes at 85.8, 101.4, and
      110.6 cm(-1) are external in which the molecules of the unit cell vibrate against
      each other in either translational or librational motions (or some linear
      combination thereof). All of the modes above 320 cm(-1) are predominantly
      internal stretching modes. The remaining modes below 320 cm(-1) include external
      modes and internal modes, mostly involving either torsional or bending motions of
      groups of atoms within a molecule.

PMID- 24738571
TI  - Anti-desmoglein antibody-negative paraneoplastic pemphigus successfully treated
      with rituximab.

PMID- 24738572
TI  - UV-B mediated metabolic rearrangements in poplar revealed by non-targeted
      metabolomics.
AB  - Plants have to cope with various abiotic stresses including UV-B radiation (280
      315 nm). UV-B radiation is perceived by a photoreceptor, triggers morphological
      responses and primes plant defence mechanisms such as antioxidant levels,
      photoreapir or accumulation of UV-B screening pigments. As poplar is an important
      model system for trees, we elucidated the influence of UV-B on overall metabolite
      patterns in poplar leaves grown under high UV-B radiation. Combining non-targeted
      metabolomics with gas exchange analysis and confocal microscopy, we aimed
      understanding how UV-B radiation triggers metabolome-wide changes, affects
      isoprene emission, photosynthetic performance, epidermal light attenuation and
      finally how isoprene-free poplars adjust their metabolome under UV-B radiation.
      Exposure to UV-B radiation caused a comprehensive rearrangement of the leaf
      metabolome. Several hundreds of metabolites were up- and down-regulated over
      various pathways. Our analysis, revealed the up-regulation of flavonoids,
      anthocyanins and polyphenols and the down-regulation of phenolic precursors in
      the first 36 h of UV-B treatment. We also observed a down-regulation of steroids
      after 12 h. The accumulation of phenolic compounds leads to a reduced light
      transmission in UV-B-exposed plants. However, the accumulation of phenolic
      compounds was reduced in non-isoprene-emitting plants suggesting a metabolic- or
      signalling-based interaction between isoprenoid and phenolic pathways. 

PMID- 24738573
TI  - Cord blood procalcitonin and Interleukin-6 are highly sensitive and specific in
      the prediction of early-onset sepsis in preterm infants.
AB  - We studied the predictive value of cord blood procalcitonin (PCT) and interleukin
      6 (IL-6) in the diagnosis of early-onset sepsis (EOS) in the preterm infant.
      Retrospectively, PCT and IL-6 were correlated with clinical and/or blood culture
      positive EOS and negative infectious status between February 2008 and March 2011.
      Receiver operating curves (ROC) were generated and the area under the curve (AUC)
      was calculated by use of Youden's Index to detect the best cut-off values for
      sensitivity and specificity. Thirty of 218 preterm infants (13.8%) were diagnosed
      as having EOS. The optimal cut-off value for PCT was 0.235 MUg/L (sensitivity
      78.6%, specificity 86.3%), and for IL-6 15.85 ng/L (sensitivity 73.7%,
      specificity 84.2%), the combination of PCT and IL-6 revealed sensitivity 77.1%
      and specificity 91.7%. The combined determination of PCT and IL-6 from cord blood
      was highly sensitive and specific in the prediction of EOS.

PMID- 24738575
TI  - Atomic-layer electroless deposition: a scalable approach to surface-modified
      metal powders.
AB  - Palladium has a number of important applications in energy and catalysis in which
      there is evidence that surface modification leads to enhanced properties. A
      strategy for preparing such materials is needed that combines the properties of
      (i) scalability (especially on high-surface-area substrates, e.g. powders); (ii)
      uniform deposition, even on substrates with complex, three-dimensional features;
      and (iii) low-temperature processing conditions that preserve nanopores and other
      nanostructures. Presented herein is a method that exhibits these properties and
      makes use of benign reagents without the use of specialized equipment. By
      exposing Pd powder to dilute hydrogen in nitrogen gas, sacrificial surface PdH is
      formed along with a controlled amount of dilute interstitial hydride. The lattice
      expansion that occurs in Pd under higher H2 partial pressures is avoided. Once
      the flow of reagent gas is terminated, addition of metal salts facilitates
      controlled, electroless deposition of an overlayer of subnanometer thickness.
      This process can be cycled to create thicker layers. The approach is carried out
      under ambient processing conditions, which is an advantage over some forms of
      atomic layer deposition. The hydride-mediated reaction is electroless in that it
      has no need for connection to an external source of electrical current and is
      thus amenable to deposition on high-surface-area substrates having rich,
      nanoscale topography as well as on insulator-supported catalyst particles. STEM
      EDS measurements show that conformal Rh and Pt surface layers can be formed on Pd
      powder with this method. A growth model based on energy-resolved XPS depth
      profiling of Rh-modified Pd powder is in general agreement. After two cycles,
      deposits are consistent with 70-80% coverage and a surface layer with a thickness
      from 4 to 8 A. 

PMID- 24738574
TI  - Systematic review: The use of thiopurines or anti-TNF in post-operative Crohn's
      disease maintenance--progress and prospects.
AB  - BACKGROUND: Post-operative recurrence of Crohn's disease is an important
      management challenge, with 2-year recurrence rates defined by clinical,
      endoscopic and radiological parameters of up to 77%, 64% and 49%. Clinical and
      severe endoscopic recurrence vary widely in controlled trials from 13% to 36% and
      22% to 56% with thiopurine treatment or 0% and 9% with infliximab treatment
      respectively at 1 year. AIMS: To provide a review of the evidence for thiopurine
      or anti-TNF use in post-operative Crohn's disease, and to assess the ability to
      identify those patients at highest risk of recurrent disease. METHODS: A
      literature search was undertaken using Medline, Embase and Cochrane databases to
      identify studies using search terms 'thiopurine', 'azathioprine',
      'mercaptopurine', 'Infliximab', 'adalimumab', 'Anti-TNF', 'Crohn's disease',
      'post-operative' and 'recurrence'. RESULTS: Trials to examine this important area
      have proved difficult to execute, with recruitment and retention of patients
      posing major challenges to randomised clinical trials. There have been four RCTs
      of 433 patients of thiopurine therapy (with three meta-analyses of these data),
      and one of anti-TNF therapy involving 24 patients. Overall the efficacy data for
      thiopurine use in this setting are inconclusive, and other than smoking, there
      are no consistent predictors of post-operative relapse. CONCLUSIONS: At present,
      evidence for routine use of thiopurine treatment in post-operative Crohn's
      disease is heterogeneous and unconvincing. Stratification by risk of relapse
      emerges as a key challenge in post-operative management that needs to be
      addressed, using clinical parameters and emerging biomarkers. The evidence for
      prophylactic anti-TNF use is limited though promising, with its routine use
      guided by early assessment of relapse.

PMID- 24738576
TI  - G2(+)M study on N-alkylamino cation affinities of neutral main-group element
      hydrides: trends across the periodic table.
AB  - We have made an extensive theoretical exploration of gas-phase N-alkylamino
      cation affinities (NAAMCA), including amino cation affinities (AMCA) and N
      dimethylamino cation affinities (NDMAMCA), of neutral main-group element hydrides
      of groups 15-17 and periods 2-4 in the periodic table by using the G2(+)M method.
      Some similarities and differences are found between NAAMCA and the corresponding
      alkyl cation affinities (ACA) of H(n)X. Our calculations show that the AMCA and
      NDMAMCA are systematically lower than the corresponding proton affinities (PA)
      for H(n)X. In general, there is no linear correlation between NAAMCA and PA of
      H(n)X. Instead, the correlations exist only within the central elements X in
      period 2, or periods 3-4, which is significantly different from the reasonable
      correlations between ACA and PA for all H(n)X. NAAMCA (H(n)X) are weaker than
      NAAMCA (H(n-1)X(-)) by more than 700 kJ/mol and generally stronger than ACA
      (H(n)X), with three exceptions: H2ONR2(+)(R = H, Me) and HFNH2(+). These new
      findings can be rationalized by the negative hyperconjugation and Pauli
      repulsion.

PMID- 24738577
TI  - Design and analysis of clinical trials of nutrients: commentary.

PMID- 24738578
TI  - What drives junior doctors to become involved in medical education?

PMID- 24738580
TI  - Statistical model selection for Markov models of biomolecular dynamics.
AB  - Markov state models provide a powerful framework for the analysis of biomolecular
      conformation dynamics in terms of their metastable states and transition rates.
      These models provide both a quantitative and comprehensible description of the
      long-time scale dynamics of large molecular dynamics with a Master equation and
      have been successfully used to study protein folding, protein conformational
      change, and protein-ligand binding. However, to achieve satisfactory performance,
      existing methodologies often require expert intervention when defining the
      model's discrete state space. While standard model selection methodologies focus
      on the minimization of systematic bias and disregard statistical error, we show
      that by consideration of the states' conditional distribution over conformations,
      both sources of error can be balanced evenhandedly. Application of techniques
      that consider both systematic bias and statistical error on two 100 MUs molecular
      dynamics trajectories of the Fip35 WW domain shows agreement with existing
      techniques based on self-consistency of the model's relaxation time scales with
      more suitable results in regimes in which those time scale-based techniques
      encourage overfitting. By removing the need for expert tuning, these methods
      should reduce modeling bias and lower the barriers to entry in Markov state model
      construction. 

PMID- 24738579
TI  - Associations between glucosamine and chondroitin supplement use and biomarkers of
      systemic inflammation.
AB  - OBJECTIVES: Glucosamine and chondroitin supplements have been shown to have anti
      inflammatory properties in both in vitro studies and animal models; however,
      little is known about these relationships in humans. The VITamins and Lifestyle
      (VITAL) biomarker study evaluated the associations between use of these
      supplements and a panel of circulating inflammatory biomarkers. DESIGN: Study
      participants included 217 men and women age 50-75 years living in the Seattle
      metropolitan area. Use of glucosamine and chondroitin supplements was ascertained
      by home interview/supplement inventory. Inflammation was assessed by using blood
      and urine collected at the time of home interview. Measures of systemic
      inflammation included plasma high-sensitivity C-reactive protein (hsCRP),
      interleukin (IL)-1beta, IL-6, IL-8, tumor necrosis factor (TNF)-alpha, soluble
      TNF receptors I and II, and urinary prostaglandin E2-metabolite (PGE-M).
      Multivariate-adjusted linear regression was used to evaluate the associations
      between supplement use and biomarkers of inflammation. RESULTS: High users (14 or
      more pills/week) of chondroitin had 36% lower hsCRP (ratio, 0.64; 95% confidence
      interval [CI], 0.39-1.04; p for trend=.03) and 27% lower PGE-M (ratio, 0.73; 95%
      CI, 0.5-0.98; p for trend=.07) than nonusers. Compared with nonusers, high users
      of glucosamine had 28% lower hsCRP (ratio, 0.72; 95% CI, 0.47-1.08; p for
      trend=.09) and 24% lower PGE-M (ratio, 0.76; 95% CI, 0.59-0.97; p for
      trend=0.10). Use of glucosamine and chondroitin supplements was not associated
      with the other markers of inflammation. CONCLUSIONS: These results support prior
      research suggesting that use of glucosamine and chondroitin is associated with
      reduced hsCRP and PGE2, but further work is needed to more definitively evaluate
      the anti-inflammatory potential of these supplements.

PMID- 24738581
TI  - Identification of (R)-6-(1-(4-cyano-3-methylphenyl)-5-cyclopentyl-4,5-dihydro-1H
      pyrazol-3-yl)-2-methoxynicotinic acid, a highly potent and selective nonsteroidal
      mineralocorticoid receptor antagonist.
AB  - A novel series of nonsteroidal mineralocorticoid receptor (MR) antagonists
      identified as part of our strategy to follow up on the clinical candidate PF
      03882845 (2) is reported. Optimization departed from the previously described
      pyrazoline 3a and focused on improving the selectivity for MR versus the
      progesterone receptor (PR) as an approach to avoid potential sex-hormone-related
      adverse effects and improving biopharmaceutical properties. From this effort, (R)
      14c was identified as a potent nonsteroidal MR antagonist (IC50 = 4.5 nM) with
      higher than 500-fold selectivity versus PR and other related nuclear hormone
      receptors, with improved solubility as compared to 2 and pharmacokinetic
      properties suitable for oral administration. (R)-14c was evaluated in vivo using
      the increase of urinary Na(+)/K(+) ratio in rat as a mechanism biomarker of MR
      antagonism. Treatment with (R)-14c by oral administration resulted in significant
      increases in urinary Na(+)/K(+) ratio and demonstrated this novel compound acts
      as an MR antagonist. 

PMID- 24738582
TI  - Selective boryl silyl ether formation in the photoreaction of
      bisboryloxide/boroxine with hydrosilane catalyzed by a transition-metal carbonyl
      complex.
AB  - Selective B-O-Si bond formation was achieved in the reaction of bisboryloxide
      O(Bpin)2 (pin = (OCMe2)2)/boroxine (MeBO)3 system with tertiary silane R3SiH in
      the presence of stoichiometric water and a catalytic amount of [M](CO)5 ([M] =
      Mo(CO), W(CO), Fe) to give boryl silyl ethers. Moreover, this reaction can be
      applied to various hydrosilanes (disilyl compounds and secondary silanes) and
      hydrogermane. Some of the boryl silyl ethers thus formed were confirmed by X-ray
      analysis. 

PMID- 24738583
TI  - Aggressive and acute periodontal diseases.
AB  - Inflammatory periodontal diseases are highly prevalent, although most of these
      diseases develop and progress slowly, often unnoticed by the affected individual.
      However, a subgroup of these diseases include aggressive and acute forms that
      have a relatively low prevalence but show a rapid-course, high rate of
      progression leading to severe destruction of the periodontal tissues, or cause
      systemic symptoms that often require urgent attention from healthcare providers.
      Aggressive periodontitis is an early-onset, destructive disease that shows a high
      rate of periodontal progression and distinctive clinical features. A contemporary
      case definition of this disease is presented. Population studies show that the
      disease is more prevalent in certain geographic regions and ethnic groups.
      Aggressive periodontitis is an infectious disease, and recent data show that in
      affected subjects the subgingival microbiota is composed of a mixed microbial
      infection, with a wide heterogeneity in the types and proportions of
      microorganisms recovered. Furthermore, there are significant differences in the
      microbiota of the disease among different geographic regions and ethnicities.
      There is also evidence that the Aggregatibacter actinomycetemycomitans-JP2 clone
      may play an important role in the development of the disease in certain
      populations. The host response plays an important role in the susceptibility to
      aggressive periodontitis, where the immune response may be complex and involve
      multiple mechanisms. Also, genetic factors seem to play an important role in the
      pathogenesis of this disease, but the mechanisms of increased susceptibility are
      complex and not yet fully understood. The available data suggest that aggressive
      periodontitis is caused by mutations either in a few major genes or in multiple
      small-effect genes, and there is also evidence of gene-gene and gene-environment
      interaction effects. Diagnostic methods for this disease, based on a specific
      microbiologic, immunologic or genetic profile, currently do not exist. Genetic
      markers have the potential to be implemented as screening tools to identify
      subjects at risk. This approach may significantly enhance treatment outcome
      through the early detection and treatment of affected subjects, as well as using
      future approaches based on gene therapy. At present, the treatment of this
      disease is directed toward elimination of the subgingival bacterial load and
      other local risk factors. Adjunctive use of appropriate systemic antibiotics is
      recommended and may contribute to a longer suppression of the microbial
      infection. Other aggressive forms of periodontal diseases occur in patients who
      are affected with certain systemic diseases, including the leukocyte adhesion
      deficiency syndrome, Papillon-Lefevre syndrome, Chediak-Higashi syndrome and Down
      syndrome. Management of the periodontal component of these diseases is very
      challenging. Acute gingival and periodontal lesions include a group of disorders
      that range from nondestructive to destructive forms, and these lesions are
      usually associated with pain and are a common reason for emergency dental
      consultations. Some of these lesions may cause a rapid and severe destruction of
      the periodontal tissues and loss of teeth. Oral infections, particularly acute
      infections, can spread to extra-oral sites and cause serious medical
      complications, and even death. Hence, prompt diagnosis and treatment are
      paramount. 

PMID- 24738584
TI  - Aggressive periodontitis: case definition and diagnostic criteria.
AB  - Aggressive periodontitis is a destructive disease characterized by the following:
      the involvement of multiple teeth with a distinctive pattern of periodontal
      tissue loss; a high rate of disease progression; an early age of onset; and the
      absence of systemic diseases. In some patients periodontal tissue loss may
      commence before puberty, whereas in most patients the age of onset is during or
      somewhat after the circumpubertal period. Besides infection with specific
      microorganisms, a host predisposition seems to play a key role in the
      pathogenesis of aggressive periodontitis, as evidenced by the familial
      aggregation of the disease. In this article we review the historical background
      of the diagnostic criteria of aggressive periodontitis, present a contemporary
      case definition and describe the clinical parameters of the disease. At present,
      the diagnosis of aggressive periodontitis is achieved using case history,
      clinical examination and radiographic evaluation. The data gathered using these
      methods are prone to relatively high measurement errors. Besides, this diagnostic
      approach measures past disease history and may not reliably measure existing
      disease activity or accurately predict future tissue loss. A diagnosis is often
      made years after the onset of the disease, partly because current assessment
      methods detect established disease more readily and reliably than they detect
      incipient or initial lesions where the tissue loss is minimal and usually below
      the detection threshold of present examination methods. Future advancements in
      understanding the pathogenesis of this disease may contribute to an earlier
      diagnosis. Insofar, future case definitions may involve the identification of key
      etiologic and risk factors, combined with high-precision methodologies that
      enable the early detection of initial lesions. This may significantly enhance the
      predictive value of these tests and detect cases of aggressive periodontitis
      before significant tissue loss develops. 

PMID- 24738585
TI  - Epidemiology and demographics of aggressive periodontitis.
AB  - Epidemiologic studies of aggressive periodontitis have used different study
      designs and a range of examination methods and case definitions, and this greatly
      complicates the study of disease prevalence in populations. The wide range of
      disease case definitions, in particular, profoundly impacts the reported rate of
      disease, and the use of a standard disease definition is strongly recommended.
      Surveys of aggressive periodontitis that use only clinical examinations, without
      radiographic examination to confirm the presence of a distinctive pattern of
      tissue loss, may overestimate the prevalence of this disease, particularly when a
      low threshold of attachment loss is used. The prevalence of aggressive
      periodontitis varies significantly between populations, and differences in
      race/ethnicities seem to be a key factor. Studies consistently show that
      aggressive periodontitis is most prevalent in Africa and in populations of
      African descent and is least prevalent in Caucasians in Europe and North America.
      Among children and young adults the prevalence of this disease is higher in older
      than in younger age groups. Most studies show comparable disease prevalence in
      male and female subjects. These findings show that aggressive periodontitis is a
      significant health problem in certain populations. This review also highlights a
      lack of information on the epidemiology and demographics of this disease in many
      parts of the world, particularly in Asia and Africa. Epidemiologic studies of
      aggressive periodontitis in high-risk populations are important and could provide
      vital data on the determinants of this disease, and this information is needed
      for the establishment of effective health-promotion measures. 

PMID- 24738586
TI  - Microbiology of aggressive periodontitis.
AB  - For decades, Aggregatibacter actinomycetemcomitans has been considered the most
      likely etiologic agent in aggressive periodontitis. Implementation of DNA-based
      microbiologic methodologies has considerably improved our understanding of the
      composition of subgingival biofilms, and advanced open-ended molecular techniques
      even allow for genome mapping of the whole bacterial spectrum in a sample and
      characterization of both the cultivable and not-yet-cultivable microbiota
      associated with periodontal health and disease. Currently, A.
      actinomycetemcomitans is regarded as a minor component of the resident oral
      microbiota and as an opportunistic pathogen in some individuals. Its specific JP2
      clone, however, shows properties of a true exogenous pathogen and has an
      important role in the development of aggressive periodontitis in certain
      populations. Still, limited data exist on the impact of other microbes
      specifically in aggressive periodontitis. Despite a wide heterogeneity of
      bacteria, especially in subgingival samples collected from patients, bacteria of
      the red complex in particular, and those of the orange complex, are considered as
      potential pathogens in generalized aggressive periodontitis. These types of
      bacterial findings closely resemble those found for chronic periodontitis,
      representing a mixed polymicrobial infection without a clear association with any
      specific microorganism. In aggressive periodontitis, the role of novel and not
      yet-cultivable bacteria has not yet been elucidated. There are geographic and
      ethnic differences in the carriage of periodontitis-associated microorganisms,
      and they need to be taken into account when comparing study reports on
      periodontal microbiology in different study populations. In the present review,
      we provide an overview on the colonization of potential periodontal pathogens in
      childhood and adolescence, and on specific microorganisms that have been
      suspected for their role in the initiation and progression of aggressive forms of
      periodontal disease. 

PMID- 24738587
TI  - Host response in aggressive periodontitis.
AB  - It is critical to understand the underlying host responses in aggressive
      periodontitis to provide a better appreciation of the risk and susceptibility to
      this disease. Such knowledge may elucidate the etiology and susceptibility to
      aggressive periodontitis and directly influence treatment decisions and aid
      diagnosis. This review is timely in that several widely held tenets are now
      considered unsupportable, namely the concept that Aggregatibacter
      actinomycetemycomitans is the key pathogen and that chemotactic defects in
      polymorphonuclear leukocytes are part of the etiopathology. This review also
      serves to put into context key elements of the host response that may be
      implicated in the genetic background of aggressive periodontitis. Furthermore,
      key molecules unique to the host response in aggressive periodontitis may have
      diagnostic utility and be used in chairside clinical activity tests or as
      population screening markers. It is becoming increasingly appreciated that the
      microbial etiology of aggressive periodontitis and the histopathology of this
      disease are more similar to than different from that of chronic periodontitis. An
      important therapeutic consideration from the lack of support for A.
      actinomycetemycomitans as a critical pathogen here is that the widely held belief
      that tetracycline had a role in aggressive periodontitis therapy is now not
      supported and that antibiotics such as those used effectively in chronic
      periodontitis (metronidazole and amoxicillin) are not contraindicated.
      Furthermore, A. actinomycetemycomitans-related molecules, such as cytolethal
      distending toxin and leukotoxin, are less likely to have utility as diagnosis
      agents or as therapeutic targets. 

PMID- 24738588
TI  - Role of genetic factors in the pathogenesis of aggressive periodontitis.
AB  - This article critically reviews the evidence for a role of genetic factors in the
      pathogenesis of aggressive periodontitis and discusses the study approaches
      commonly used to identify genetic risk factors of this disease. Available data
      suggest that aggressive periodontitis is caused by mutations in multiple genes,
      combined with environmental effects. Syndromic periodontal diseases include
      certain monogenic disorders that express phenotypes showing aggressive forms of
      periodontitis, and the genetic triggering factors of most of these syndromes have
      been identified. Other periodontal disease phenotypes seem to occur through
      different genetic predisposition patterns. Case-control and genome-wide studies
      have been used to investigate the association with gene polymorphisms.
      Association studies and the familial aggregation of aggressive periodontitis
      suggest a significant genetic component in the increased predisposition to this
      disease. There is evidence to support the contribution of a few major genes or of
      multiple small-effects genes. In addition, there is evidence of gene-gene and
      gene-environment interaction effects. Early studies suggested an X-linked mode of
      transmission of aggressive periodontitis, and subsequent studies support an
      autosomal mode. Genetic studies have the potential to improve the screening
      programs of subjects at risk for developing aggressive periodontitis and may
      enhance treatment outcome through gene therapy. 

PMID- 24738589
TI  - Treatment of aggressive periodontitis.
AB  - Despite etiological differences between aggressive and chronic periodontitis, the
      treatment concept for aggressive periodontitis is largely similar to that for
      chronic periodontitis. The goal of treatment is to create a clinical condition
      that is conducive to retaining as many teeth as possible for as long as possible.
      When a diagnosis has been made and risk factors have been identified, active
      treatment is commenced. The initial phase of active treatment consists of
      mechanical debridement, either alone or supplemented with antimicrobial drugs.
      Scaling and root planing has been shown to be effective in improving clinical
      indices, but does not always guarantee long-term stability. Antimicrobials can
      play a significant role in controlling aggressive periodontitis. Few studies have
      been published on this subject for localized aggressive periodontitis, but
      generalized aggressive periodontitis has been subject to more scrutiny. Studies
      have demonstrated that systemic antibiotics as an adjuvant to scaling and root
      planing are more effective in controlling disease compared with scaling and root
      planing alone or with supplemental application of local antibiotics or
      antiseptics. It has also become apparent that antibiotics ought to be
      administered with, or just after, mechanical debridement. Several studies have
      shown that regimens of amoxicillin combined with metronidazole or regimens of
      clindamycin are the most effective and are preferable to regimens containing
      doxycycline. Azithromycin has been shown to be a valid alternative to the regimen
      of amoxicillin plus metronidazole. A limited number of studies have been
      published on surgical treatment in patients with aggressive periodontitis, but
      the studies available show that the effect can be comparable with the effect on
      patients with chronic periodontitis, provided that proper oral hygiene is
      maintained, a strict maintenance program is followed and modifiable risk factors
      are controlled. Both access surgery and regenerative techniques have shown good
      results in patients with aggressive periodontitis. Once good periodontal health
      has been obtained, patients must be enrolled in a strict maintenance program that
      is directed toward controlling risk factors for disease recurrence and tooth
      loss. The most significant risk factors are noncompliance with regular
      maintenance care, smoking, high gingival bleeding index and poor plaque control.
      There is no evidence to suggest that daily use of antiseptic agents should be
      part of the supportive periodontal therapy for aggressive periodontitis. 

PMID- 24738590
TI  - Aggressive forms of periodontitis secondary to systemic disorders.
AB  - A number of systemic disorders increase a patient's susceptibility to destructive
      periodontitis and have impacts on periodontal disease progression and severity.
      The underlying factors are usually genetic and are mainly related to alterations
      in the immune response and in certain endocrine functions, leading to various
      syndromes in which periodontitis and/or early tooth loss are secondary
      manifestations. Neutrophils are important immune defense cells that play a
      significant role in controlling the spread of microbial plaque infections in the
      dentogingival region. This review focuses on a selected group of systemic
      disorders that are associated with alterations in either neutrophil counts
      (quantitative disorders) or function (qualitative disorders), and defects in the
      mineralization of bone and dental tissues. In most of these diseases controlling
      the periodontal disease progression is very challenging. Proper diagnosis is a
      prerequisite for proper management of the periodontal problem. Future advances in
      research, including gene targeting and the resolution of enzyme deficiencies, may
      bring about remedies of the underlying systemic disorders and may significantly
      improve the outcome of periodontal treatment in these patients. 

PMID- 24738591
TI  - Acute periodontal lesions.
AB  - This review provides updates on acute conditions affecting the periodontal
      tissues, including abscesses in the periodontium, necrotizing periodontal
      diseases and other acute conditions that cause gingival lesions with acute
      presentation, such as infectious processes not associated with oral bacterial
      biofilms, mucocutaneous disorders and traumatic and allergic lesions. A
      periodontal abscess is clinically important because it is a relatively frequent
      dental emergency, it can compromise the periodontal prognosis of the affected
      tooth and bacteria within the abscess can spread and cause infections in other
      body sites. Different types of abscesses have been identified, mainly classified
      by their etiology, and there are clear differences between those affecting a pre
      existing periodontal pocket and those affecting healthy sites. Therapy for this
      acute condition consists of drainage and tissue debridement, while an evaluation
      of the need for systemic antimicrobial therapy will be made for each case, based
      on local and systemic factors. The definitive treatment of the pre-existing
      condition should be accomplished after the acute phase is controlled. Necrotizing
      periodontal diseases present three typical clinical features: papilla necrosis,
      gingival bleeding and pain. Although the prevalence of these diseases is not
      high, their importance is clear because they represent the most severe conditions
      associated with the dental biofilm, with very rapid tissue destruction. In
      addition to bacteria, the etiology of necrotizing periodontal disease includes
      numerous factors that alter the host response and predispose to these diseases,
      namely HIV infection, malnutrition, stress or tobacco smoking. The treatment
      consists of superficial debridement, careful mechanical oral hygiene, rinsing
      with chlorhexidine and daily re-evaluation. Systemic antimicrobials may be used
      adjunctively in severe cases or in nonresponding conditions, being the first
      option metronidazole. Once the acute disease is under control, definitive
      treatment should be provided, including appropriate therapy for the pre-existing
      gingivitis or periodontitis. Among other acute conditions affecting the
      periodontal tissues, but not caused by the microorganisms present in oral
      biofilms, infectious diseases, mucocutaneous diseases and traumatic or allergic
      lesions can be listed. In most cases, the gingival involvement is not severe;
      however, these conditions are common and may prompt an emergency dental visit.
      These conditions may have the appearance of an erythematous lesion, which is
      sometimes erosive. Erosive lesions may be the direct result of trauma or a
      consequence of the breaking of vesicles and bullae. A proper differential
      diagnosis is important for adequate management of the case. 

PMID- 24738592
TI  - Acute focal infections of dental origin.
AB  - This article describes the most important pus-producing acute oral infections
      (dental infections) that can spread extra-orally. Most of these infections are
      spread by bacteria entering the bloodstream. However, dental infections have a
      number of other pathways for dissemination. By forming abscesses or phlegmon they
      can reach facial spaces that communicate with each other and then spread
      downwards to the mediastinum or upwards to the brain. In such cases dental
      infections can become, if not properly treated, life-threatening. It seems that
      early diagnosis and treatment are imperative, and potentially infectious foci
      should be traced and eliminated. Dental hygiene and prophylaxis to prevent dental
      biofilm formation are important measures to reduce the risk of these calamities.
      The more compromised the host defense is, the more importance should be put on
      these measures. Although commensal bacteria are often involved in these
      infections, attention should also be paid to specific periodontal pathogens, and
      a proper microbial diagnosis, obtained using molecular methods plus bacterial
      sensitivity testing, can provide the patient with optimal care. Drainage of pus
      must be established where possible so that the optimal effect of antibiotics can
      be achieved. Penicillin is still the drug of first choice in settings where
      suspicion of methicillin-resistant Staphylococcus aureus is low. 

PMID- 24738593
TI  - Ceramide synthase 4 deficiency in mice causes lipid alterations in sebum and
      results in alopecia.
AB  - Five ceramide synthases (CerS2-CerS6) are expressed in mouse skin. Although CerS3
      has been shown to fulfill an essential function during skin development, neither
      CerS6- nor CerS2-deficient mice show an obvious skin phenotype. In order to study
      the role of CerS4, we generated CerS4-deficient mice (Cers4-/-) and CerS4
      specific antibodies. With these biological tools we analysed the tissue
      distribution and determined the cell-type specific expression of CerS4 in
      suprabasal epidermal layers of footpads as well as in sebaceous glands of the
      dorsal skin. Loss of CerS4 protein leads to an altered lipid composition of the
      sebum, which is more solidified and therefore might cause progressive hair loss
      due to physical blocking of the hair canal. We also noticed a strong decrease in
      C20 1,2-alkane diols consistent with the decrease of wax diesters in the sebum of
      Cers4-/- mice. Cers4-/- mice at 12 months old display additional epidermal tissue
      destruction due to dilated and obstructed pilary canals. Mass spectrometric
      analyses additionally show a strong decrease in C20-containing sphingolipids. 

PMID- 24738595
TI  - Expectations and limitations of contemporary intravascular imaging: lessons
      learned from pathology.
AB  - Acute coronary syndrome is the leading cause of death worldwide and plaque
      rupture is the most common underlying mechanism of coronary thrombosis. During
      the last 2 decades the understanding of atherosclerotic plaque progression
      advanced dramatically and pathology studies provided fundamental insights of
      underlying plaque morphology, which paved the way for invasive imaging
      modalities, which bring a new area of atherosclerotic plaque characterization in
      vivo. The development of intravascular ultrasound (IVUS) allowed the field to
      evaluate the principles of vascular anatomy, which is often underestimated by
      coronary angiography. Furthermore, IVUS image technologies were developed to
      obtain improved characterization of plaque composition. However, since spatial
      resolution of IVUS is insufficient to distinguish details of plaque morphology, a
      broad adoption of this technology in clinical practice was missing. Optical
      coherence tomography is a light-based imaging modality with higher spatial
      resolution compared to IVUS, which enables the assessment of vascular anatomy
      with great detail. 

PMID- 24738594
TI  - Diversity and genomic insights into the uncultured Chloroflexi from the human
      microbiota.
AB  - Many microbial phyla that are widely distributed in open environments have few or
      no representatives within animal-associated microbiota. Among them, the
      Chloroflexi comprises taxonomically and physiologically diverse lineages adapted
      to a wide range of aquatic and terrestrial habitats. A distinct group of
      uncultured chloroflexi related to free-living anaerobic Anaerolineae inhabits the
      mammalian gastrointestinal tract and includes low-abundance human oral bacteria
      that appear to proliferate in periodontitis. Using a single-cell genomics
      approach, we obtained the first draft genomic reconstruction for these organisms
      and compared their inferred metabolic potential with free-living chloroflexi.
      Genomic data suggest that oral chloroflexi are anaerobic heterotrophs, encoding
      abundant carbohydrate transport and metabolism functionalities, similar to those
      seen in environmental Anaerolineae isolates. The presence of genes for a unique
      phosphotransferase system and N-acetylglucosamine metabolism suggests an
      important ecological niche for oral chloroflexi in scavenging material from lysed
      bacterial cells and the human tissue. The inferred ability to produce sialic acid
      for cell membrane decoration may enable them to evade the host defence system and
      colonize the subgingival space. As with other low abundance but persistent
      members of the microbiota, discerning community and host factors that influence
      the proliferation of oral chloroflexi may help understand the emergence of oral
      pathogens and the microbiota dynamics in health and disease states. 

PMID- 24738596
TI  - Ketorolac tromethamine - routes and clinical implications.
AB  - Opioids have long been used for analgesic purposes for a wide range of
      procedures. However, the binding of these drugs to opiate receptors has created
      various challenges to the clinician due to unfavorable side effect profiles and
      the potential for tolerance and abuse. In 1989, ketorolac became an approved
      nonsteroidal inflammatory drug (NSAID) for injectable use as an analgesic. Over
      the last 20 years, numerous studies have been conducted involving ketorolac.
      These studies have provided additional information about various routes of
      administration and their effect on the efficacy and the side effect profile of
      ketorolac. Moreover, ketorolac has been compared with several widely used
      analgesics. This review evaluates both the potential benefits and potential
      drawbacks of ketorolac generally, and specifically discusses routes of
      administration, including their advantages and disadvantages when compared to
      several traditional analgesics in both inpatient and outpatient settings.

PMID- 24738597
TI  - From UVR8 to flavonol synthase: UV-B-induced gene expression in Sauvignon blanc
      grape berry.
AB  - The aim of this research was to determine the effect of development and UV-B on
      flavonols and the regulation of gene activity in Vitis vinifera L. var. Sauvignon
      blanc grapes. Particular emphasis was placed on gene activity associated with the
      low and high fluence UV-B responses. Flavonols, particularly quercetin and
      kaempferol glycosides, increased substantially upon fruit exposure due to UV-B,
      with spatial analysis locating the changes to the berry skin. Of five VvFLS genes
      in grapes, two (VvFLS4 and 5) were found to be transcriptionally active, with
      VvFLS4 also being responsive to UV-B but VvFLS5 was not. Of the transcription
      factors known to regulate FLS (VvMYB12, VvMYCA1 and VvWDRs), only VvMYB12 was
      found to be responsive to UV-B. A number of candidate genes associated with the
      low and high UV-B fluence responses were also studied (VvUVR8, VvHY5, VvCOP1 and
      VvCHS; PR genes and VvMAPK3; respectively). The genes associated with the low
      fluence response exhibited transcriptional regulation in line with reports from
      other species, while the PR genes and VvMAPK3 only appeared to be responsive in a
      high UV-B fluence environment. Together, these data supports the view flavonol
      biosynthesis in grape is stimulated predominantly through the low fluence UV-B
      response pathway. 

PMID- 24738598
TI  - Coexistence of three variants of cutaneous mastocytosis as the presenting sign of
      systemic mastocytosis with somatic c-kit D816V point mutation.

PMID- 24738605
TI  - CO and CO2 fixation by Se-Ru-CO hydride clusters.
AB  - The selective insertion of CO and CO2 into the C-O and O-H bonds of alcohols by
      the Se-Ru-CO hydride clusters [(MU-H)Ru4(CO)10Se2](-) (1) and [(MU3
      H)Ru5(CO)14Se](-) (2) was demonstrated by a cooperative effect of the protonic
      hydride, the electron-rich Ru atom, and the electronegative Se atom as well as
      the symmetry of the clusters. These reactions generated the first examples of Se
      containing ruthenium carboxylate and alkylcarbonate clusters [{(MU
      H)Ru4(CO)10Se2}2{Ru2(CO)4(MU-eta(1):eta(1)-OOCR)}](3-) (R = Me, 3; Et, 4) and
      [{(MU-H)Ru4(CO)10Se2}2{Ru2(CO)4(MU-eta(1):eta(1)-OOCOR)}](3-) (R = Me, 5; Et, 6),
      respectively. These results disclosed herein provide a new avenue for the capture
      and storage of CO and CO2 and useful synthetic routes to novel RCOO(-)- and
      ROCOO(-)-bridged ruthenium selenide clusters. 

PMID- 24738606
TI  - Comparison of scoring systems and outcome of patients admitted to a liver
      intensive care unit of a tertiary referral centre with severe variceal bleeding.
AB  - BACKGROUND: Acute variceal haemorrhage (AVH) is associated with significant
      mortality. AIMS: To determine outcome and factors associated with hospital
      mortality (HM) in patients with AVH admitted to intensive care unit (ICU) and to
      compare outcomes of patients requiring transfer to a tertiary ICU (transfer
      group, TG) to a local in-patient group (LG). METHODS: A retrospective study of
      all adult patients (N = 177) admitted to ICU with AVH from 2000-2008 was
      performed. RESULTS: Median age was 48 years (16-80). Male represented 58%. Median
      MELD score was 16 (6-39), SOFA score was 8 (6-11). HM was higher in patients who
      had severe liver disease or critical illness measured by MELD, SOFA, APACHE II
      scores and number of failed organs (NFO), P < 0.05. Patients with day-1 lactate
      >= 2 mmol/L had increased HM (P < 0.001). MELD score performed as well as APACHE
      II, SOFA and NFO (P < 0.001) in predicting HM (AUROC = 0.84, 0.81, 0.79 and 0.82,
      respectively P > 0.05 for pair wise comparisons). Re-bleeding was associated with
      increased HM (56.9% vs. 31.6%, P = 0.002). The TG (n = 124) had less severe liver
      disease and critical illness and consequently had lower HM than local patients
      (32% vs. 57%, P = 0.002). TG patients with >=2 endoscopies prior to transfer had
      increased 6-week mortality (P = 0.03). Time from bleeding to transfer >=3 days
      was associated with re-bleeding (OR = 2.290, P = 0.043). CONCLUSIONS: MELD score
      was comparable to ICU prognostic models in predicting mortality. Blood lactate
      was also predictive of hospital mortality. Delays in referrals and repeated
      endoscopy were associated with increased re-bleeding and mortality in this group.

PMID- 24738607
TI  - An extremely rare cause of gastric outlet: breast lobular carcinoma metastases to
      stomach.

PMID- 24738608
TI  - The spectrum of skin diseases in a black population in Durban, KwaZulu-Natal,
      South Africa.
AB  - BACKGROUND: Precise knowledge of the prevalence and spectrum of skin diseases in
      a population allows for effective planning for provision of dermatology services
      and distribution of resources. There are no published data on the epidemiology of
      skin disorders in Durban, KwaZulu-Natal. OBJECTIVE: We investigated the
      prevalence of skin diseases in black African patients attending a predominantly
      black private healthcare facility and profiled the patients. METHODS: Clinical
      charts of all black African patients seen between January 2003 and December 2010
      in a private practice in Durban were reviewed. The diseases seen were described
      and the prevalence calculated. RESULTS: A total of 6664 patient charts were
      reviewed. The five most common conditions were acne, eczemas, dyschromias,
      infections, and hair disorders. These data agree with reports from other parts of
      the world. LIMITATIONS: Selection bias was presented by a single private
      practice, thus data may not be fully representative of our population.
      CONCLUSION: Acne, eczemas, dyschromias, infections, and hair disorders are, in
      that order, the five most common disorders encountered.

PMID- 24738610
TI  - Leptin induces a proliferative response in breast cancer cells but not in normal
      breast cells.
AB  - Obesity is a risk factor for breast cancer in postmenopausal women. Leptin, a
      hormone excessively produced during obesity, is suggested to be involved in
      breast cancer. The aim of the study was to investigate procarcinogenic potential
      of leptin by evaluating influence of leptin on cell proliferation, cell cycle,
      apoptosis, and signaling on numerous breast cells lines, including 184B5 normal
      cells, MCF10A fibrocystic cells and MCF-7, MDA-MB-231, and T47D cancer cells.
      Expressions of leptin and Ob-R were analyzed using qRT-PCR and
      immunohistochemistry, proliferation using fluorimetric resazurin reduction test
      and xCELLigence system, apoptosis and cell cycle by flow cytometry, and effect of
      leptin on different signalling pathways using qRT-PCR and Western blot. Cells
      were exposed to increasing concentrations of leptin. All cell lines expressed
      mRNA and protein of leptin and Ob-R. Leptin stimulated proliferation of all cell
      lines except for 184B5 and MDA-MB-231 cells. Leptin inhibited apoptosis but
      didn't alter proportion of cells within cell cycle in MCF7 cells. Leptin induced
      overexpression of leptin, Ob-R, estrogen receptor, and aromatase mRNA in MCF-7
      and T47D cells. Autoregulation induced by leptin, relationship with estrogen
      pathway, and proliferative and antiapoptic activity in breast cancer cells may
      explain that obesity-associated hyperleptinemia may be a breast cancer risk
      factor. 

PMID- 24738609
TI  - Effectiveness and Safety of Tapentadol Prolonged Release (PR) Versus a
      Combination of Tapentadol PR and Pregabalin for the Management of Severe, Chronic
      Low Back Pain With a Neuropathic Component: A Randomized, Double-blind, Phase 3b
      Study.
AB  - OBJECTIVE: To evaluate the effectiveness and tolerability of tapentadol PR
      monotherapy versus tapentadol PR/pregabalin combination therapy for severe,
      chronic low back pain with a neuropathic component. METHODS: Eligible patients
      had painDETECT "unclear" or "positive" ratings and average pain intensity >= 6
      (11-point NRS-3 [average 3-day pain intensity]) at baseline. Patients were
      titrated to tapentadol PR 300 mg/day over 3 weeks. Patients with >= 1-point
      decrease in pain intensity and average pain intensity >= 4 were randomized to
      tapentadol PR (500 mg/day) or tapentadol PR (300 mg/day)/pregabalin (300 mg/day)
      during an 8-week comparative period. RESULTS: In the per-protocol population (n =
      288), the effectiveness of tapentadol PR was clinically and statistically
      comparable to tapentadol PR/pregabalin based on the change in pain intensity from
      randomization to final evaluation (LOCF; LSMD [95% CI], -0.066 [-0.57, 0.43]; P <
      0.0001 for noninferiority). Neuropathic pain and quality-of-life measures
      improved significantly in both groups. Tolerability was good in both groups, in
      line with prior trials in the high dose range of 500 mg/day for tapentadol PR
      monotherapy, and favorable compared with historical combination trials of strong
      opioids and anticonvulsants for combination therapy. The incidence of the
      composite of dizziness and/or somnolence was significantly lower with tapentadol
      PR (16.9%) than tapentadol PR/pregabalin (27.0%; P = 0.0302). CONCLUSIONS:
      Tapentadol PR 500 mg is associated with comparable improvements in pain intensity
      and quality-of-life measures to tapentadol PR 300 mg/pregabalin 300 mg, with
      improved central nervous system tolerability, suggesting that tapentadol PR
      monotherapy may offer a favorable treatment option for severe low back pain with
      a neuropathic component.

PMID- 24738611
TI  - Ectopic lipid storage in non-alcoholic fatty liver disease is not mediated by
      impaired mitochondrial oxidative capacity in skeletal muscle.
AB  - Non-alcoholic fatty liver disease (NAFLD), characterized by lipid deposition
      within the liver [intrahepatocellular lipid (IHCL)], is associated with insulin
      resistance and the metabolic syndrome (MS). It has been suggested that impaired
      skeletal muscle mitochondrial function may contribute to ectopic lipid
      deposition, and the associated MS, by altering post-prandial energy storage. To
      test this hypothesis, we performed a cross-sectional study of 17 patients with
      NAFLD [mean+/-S.D.; age, 45+/-11 years; body mass index (BMI), 31.6+/-3.4 kg/m2]
      and 18 age- and BMI-matched healthy controls (age, 44+/-11 years; BMI, 30.5+/-5.2
      kg/m2). We determined body composition by MRI, IHCL and intramyocellular (soleus
      and tibialis anterior) lipids (IMCLs) by proton magnetic resonance spectroscopy
      (1H-MRS) and skeletal muscle mitochondrial function by dynamic phosphorus
      magnetic resonance spectroscopy (31P-MRS) of quadriceps muscle. Although matched
      for BMI and total adiposity, after statistical adjustment for gender, patients
      with NAFLD (defined by IHCL >= 5.5%) had higher IHCLs (25+/-16% compared with 2+/
      2%; P<0.0005) and a higher prevalence of the MS (76% compared with 28%) compared
      with healthy controls. Despite this, the visceral fat/subcutaneous fat ratio,
      IMCLs and muscle mitochondrial function were similar between the NAFLD and
      control groups, with no significant difference in the rate constants of post
      exercise phosphocreatine (PCr) recovery (1.55+/-0.4 compared with 1.51+/-0.4 min
      1), a measure of muscle mitochondrial function. In conclusion, impaired muscle
      mitochondrial function does not seem to underlie ectopic lipid deposition, or the
      accompanying features of the MS, in patients with NAFLD. 

PMID- 24738612
TI  - Breast cancer: early prediction of response to neoadjuvant chemotherapy using
      parametric response maps for MR imaging.
AB  - PURPOSE: To prospectively compare the performance of dynamic contrast material
      enhanced (DCE) magnetic resonance (MR) imaging using parametric response map
      (PRM) analysis with that using pharmacokinetic parameters (transfer constant
      [K(trans)], rate constant [kep ], and relative extravascular extracellular space
      [ve]) in the early prediction of pathologic responses to neoadjuvant chemotherapy
      (NAC) in breast cancer patients. MATERIALS AND METHODS: The institutional review
      board approved this study; informed consent was obtained. Between August 2010 and
      December 2012, 48 women (mean age, 46.4 years; range, 29-65 years) with breast
      cancer were enrolled and treated with an anthracycline-taxane regimen. DCE MR
      imaging was performed before and after the first cycle of chemotherapy, and the
      pathologic response was assessed after surgery. Tumor size and volume, PRM
      characteristics, and pharmacokinetic parameters (K(trans), kep, and ve) on MR
      images were assessed and compared according to the pathologic responses by using
      the Fisher exact test or the independent-sample t test. RESULTS: Six of 48 (12%)
      patients showed pathologic complete response (CR) (pCR) and 42 (88%) showed
      nonpathologic CR (npCR). Thirty-eight (79%) patients showed a good response
      (Miller-Payne score of 3, 4, or 5), and 10 (21%) showed a minor response (Miller
      Payne score of 1 or 2). The mean proportion of voxels with increased signal
      intensity (PRMSI+) in the pCR or good response group was significantly lower than
      that in the npCR or minor response group (14.0% +/- 6.5 vs 40.7% +/- 27.2, P <
      .001; 34.3% +/- 26.4 vs 52.8% +/- 24.9, P = .041). Area under the receiver
      operating characteristic curve for PRMSI+ in the pCR group was 0.770 (95%
      confidence interval: 0.626, 0.879), and that for the good response group was
      0.716 (95% confidence interval: 0.567, 0.837). No difference in tumor size, tumor
      volume, or pharmacokinetic parameters was found between groups. CONCLUSION: PRM
      analysis of DCE MR images may enable the early identification of the pathologic
      response to NAC after the first cycle of chemotherapy, whereas pharmacokinetic
      parameters (K(trans), kep, and ve) do not.

PMID- 24738614
TI  - Long-term outcome after CT angiography in patients with possible acute coronary
      syndrome.
AB  - PURPOSE: To assess the long-term outcome and hospital readmission rate associated
      with a computed tomographic (CT) angiography-guided strategy used to examine
      patients who present to the emergency department (ED) with symptoms of possible
      acute coronary syndrome (ACS). MATERIALS AND METHODS: The study was approved by
      the institutional review board, and all patients provided written informed
      consent. A total of 585 consecutive patients (mean age, 58 years +/- 11 [standard
      deviation]; 58% were male) with ischemic-type chest pain and low to intermediate
      risk for ACS were evaluated prospectively. Patients underwent coronary CT
      angiography after single or serial troponin I (TnI) measurement, depending on
      time of presentation to the ED. Subsequent care was determined with CT
      angiography findings: Patients without plaque and patients with nonobstructive
      plaque and at most mild to moderate stenosis (<40% luminal narrowing) were
      discharged without further investigation. Patients with moderate stenosis (40%
      70% narrowing) were discharged and referred for outpatient stress
      echocardiography. Patients with severe stenosis (>70% narrowing) were admitted.
      Discharged patients were contacted and their medical records were reviewed to
      determine rates of death, ACS, revascularization, and hospital admission. By
      using binomial distribution, Clopper-Pearson confidence intervals (CIs) were
      calculated for outcome data. RESULTS: Coronary CT angiography findings were as
      follows: A total of 196 patients (34%) had no coronary plaque or stenosis, 288
      (49%) had nonobstructive plaque, 22 (4%) had moderate stenosis, and 79 (13%) had
      severe stenosis. At median 47.4-month follow-up (range, 24-57 months) of the 506
      discharged patients, five (1%; 95% CI: 0.4%, 2.3%) had been readmitted for chest
      pain; there were no instances of coronary revascularization, ACS, or death (0%
      for all; 95% CI: 0%, 0.7%). Follow-up was 100% complete. CONCLUSION: Use of a CT
      angiography-guided strategy to investigate patients with low to intermediate risk
      of ACS who present to the ED with chest pain is safe at long-term follow-up,
      including patients discharged after single TnI measurement.

PMID- 24738615
TI  - Medicinal formulations of the Kuch tribe of Bangladesh.

PMID- 24738613
TI  - The role of imaging specialists as authors of systematic reviews on diagnostic
      and interventional imaging and its impact on scientific quality: report from the
      EuroAIM Evidence-based Radiology Working Group.
AB  - PURPOSE: To evaluate the inclusion of radiologists or nuclear medicine physicians
      (imaging specialists) as authors of systematic reviews (SRs) on imaging and
      imaging-guided diagnostic procedures and to determine the impact of imaging
      specialists' presence as authors on the overall quality of the reviews. MATERIALS
      AND METHODS: A MEDLINE and EMBASE search was performed for SRs of diagnostic and
      interventional image-guided procedures that were published from January 2001 to
      December 2010. SRs about procedures primarily performed by nonimaging specialists
      were excluded. The inclusion of imaging specialists among the SR authors and the
      frequency of publication in imaging journals were evaluated. The quality of a
      subset of 200 SRs (100 most recent SRs with imaging specialists as authors and
      100 most recent SRs without imaging specialists as authors) was rated by using a
      12-item modified assessment of multiple SRs (AMSTAR) evaluation tool. Spearman,
      chi(2), and Mann-Whitney statistics were used. RESULTS: From among 3258 retrieved
      citations, 867 SRs were included in the study. Neuroimaging had the largest
      number of SRs (28% [241 of 867]), 41% (354 of 867) of SRs concerned diagnostic
      performance, and 26% (228 of 867) of SRs were published in imaging journals.
      Imaging specialists were authors (in any position) in 330 (38%) of 867 SRs; they
      were first authors of 176 SRs and last authors of 161 SRs. SRs with imaging
      specialists as authors were more often published in imaging journals than in
      nonimaging journals (54% [179 of 330] vs 9% [49 of 537]; P < .001). The median
      number of modified AMSTAR quality indicators was nine in SRs with imaging
      specialists as authors, while that in SRs without imaging specialists as authors
      was seven (P = .003). CONCLUSION: Only 38% (330 of 867) of SRs on radiology or
      nuclear medicine-related imaging published from January 2001 to December 2010
      included imaging specialists as authors. However, the inclusion of imaging
      specialists as authors was associated with a significant increase in the
      scientific quality (as judged by using a modified AMSTAR scale) of the SR.

PMID- 24738618
TI  - Synthesis of an adj-dicarbaporphyrin and the formation of an unprecedented
      tripalladium sandwich complex.
AB  - An adj-dicarbaporphyrin was prepared by carrying out a base-catalyzed MacDonald
      reaction between bis(3-indenyl)methane and a dipyrrylmethane dialdehyde. The
      porphyrinoid system exhibited highly diatropic characteristics, and the proton
      NMR spectrum gave resonances at -5.74 and -6.24 ppm for the internal NH and CH
      protons, respectively. The UV-vis spectrum was also porphyrin-like, giving a
      Soret band at 455 nm and a series of Q bands at longer wavelengths. Addition of
      trifluoroacetic acid gave a C-protonated monocation, and at higher acid
      concentrations a dicationic species was observed. Addition of 1,8
      diazabicyclo[5.4.0]undec-7-ene (DBU) afforded a monodeprotonated porphyrinoid
      anion. All of these species retained highly diatropic characteristics. Density
      functional theory calculations showed that a nonplanar tautomer with four
      internal hydrogens was favored, in agreement with the spectroscopic data. Nucleus
      independent chemical shift calculations also confirmed the aromatic
      characteristics of the free-base, cationic, and anionic structures. The
      dicarbaporphyrin reacted with palladium(II) acetate in refluxing acetonitrile to
      give an unusual tripalladium sandwich complex consisting of two dianionic
      palladium(II) dicarbaporphyrin units surrounding a palladium(IV) cation with
      unique eta(5) interactions involving meso-carbon atoms. 

PMID- 24738616
TI  - Concentration of fibrin and presence of plasminogen affect proliferation,
      fibrinolytic activity, and morphology of human fibroblasts and keratinocytes in
      3D fibrin constructs.
AB  - Fibrin is a hemostatic protein found in the clotting cascade. It is used in the
      operating room to stop bleeding and deliver cells and growth factors to heal
      wounds. However, formulations of clinically approved fibrin are optimized for
      hemostasis, and the extent to which biochemical and physical cues in fibrin
      mediate skin cell behavior is not fully understood nor utilized in the design of
      biomaterials. To determine if the concentration of fibrinogen and the presence of
      plasminogen affect cell behavior relevant to wound healing, we fabricated three
      dimensional fibrin constructs made from 5, 10, or 20 mg/mL of clinical fibrin or
      plasminogen-depleted (PD) fibrin. We cultured dermal fibroblasts or epidermal
      keratinocytes in these constructs. Fibroblasts proliferated similarly in both
      types of fibrin, but keratinocytes proliferated more in low concentrations of
      clinical fibrin and less in PD fibrin. Clinical fibrin constructs with
      fibroblasts were less stiff and degraded faster than PD fibrin constructs with
      fibroblasts. Similarly, keratinocytes degraded clinical fibrin, but not PD
      fibrin. Fibroblast spreading varied with fibrin concentration in both types of
      fibrin. In conclusion, the concentration of fibrinogen and the presence of
      plasminogen affect fibroblast and keratinocyte proliferation, morphology, and
      fibrin degradation. Creating materials with heterogeneous regions of fibrin
      formulations and concentrations could be a novel strategy for controlling the
      phenotype of encapsulated fibroblasts and keratinocytes, and the subsequent
      biomechanical properties of the construct. However, other well-investigated
      aspects of wound healing remain to be utilized in the design of fibrin
      biomaterials, such as autocrine and paracrine signaling between fibroblasts,
      keratinocytes, and immune cells. 

PMID- 24738617
TI  - Fast intracellular dissolution and persistent cellular uptake of silver
      nanoparticles in CHO-K1 cells: implication for cytotoxicity.
AB  - Toxicity of silver nanoparticles (Ag NPs) has been reported both in vitro and in
      vivo. However, the intracellular stability and chemical state of Ag NPs are still
      not very well studied. In this work, we systematically investigated the cellular
      uptake pathways, intracellular dissolution and chemical species, and cytotoxicity
      of Ag NPs (15.9 +/- 7.6 nm) in Chinese hamster ovary cell subclone K1 cells, a
      cell line recommended by the OECD for genotoxicity studies. Quantification of
      intracellular nanoparticle uptake and ion release was performed through
      inductively coupled plasma mass spectrometry. X-ray absorption near-edge
      structure (XANES) was employed to assess the chemical state of intracellular
      silver. The toxic potential of Ag NPs and Ag(+) was evaluated by cell viability,
      reactive oxygen species (ROS) production and live-dead cell staining. The results
      suggest that cellular uptake of Ag NPs involves lipid-raft-mediated endocytosis
      and energy-independent diffusion. The degradation study shows that Ag NPs taken
      up into cells dissolved quickly and XANES results directly indicated that the
      internalized Ag was oxidized to Ag-O- species and then stabilized in silver
      sulfur (Ag-S-) bonds within the cells. Subsequent cytotoxicity studies show that
      Ag NPs decrease cell viability and increase ROS production. Pre-incubation with N
      acetyl-L-cysteine, an efficient antioxidant and Ag(+) chelator, diminished the
      cytotoxicity caused by Ag NPs or Ag(+) exposure. Our study suggests that the
      cytotoxicity mechanism of Ag NPs is related to the intracellular release of
      silver ions, followed by their binding to SH-groups, presumably coming from amino
      acids or proteins, and affecting protein functions and the antioxidant defense
      system of cells.

PMID- 24738619
TI  - Myocardial recovery: a focus on the impact of left ventricular assist devices.
AB  - Heart failure remains one of the most prevalent diseases worldwide and in recent
      decades, left ventricular assist devices (LVADs) have become an important
      treatment option. With increasing device experience, there is particular interest
      in the use of LVADs as a bridge to recovery that allows the patient's heart to
      undergo reverse remodeling, whereby the device can be explanted and the heart can
      function at an improved state. There are many considerations that play a role in
      this process, including the ability of the device to unload the heart, the innate
      physiology of the heart to recover and the use of concomitant therapies. This
      review provides an overview of the most current literature as it pertains to
      these processes and gives a view into the future directions of LVADs as a tool
      for achieving myocardial recovery. 

PMID- 24738620
TI  - A universal model of restricted diffusion for fluorescence correlation
      spectroscopy.
AB  - Fluorescence correlation spectroscopy (FCS) is frequently used to study the
      processes of restricted diffusion. The most important quantity to determine is
      the size of the structures that hinder the Brownian motion of the molecules. We
      study three qualitatively different models of restricted diffusion, widely
      applied in biophysics and material science: Diffusion constrained by elastic
      force (i), walking confined diffusion (ii), and hop diffusion (iii). They cover
      the diversity of statistical behaviors, from purely Gaussian (i) to sharply non
      Gaussian on intermediate time scales (ii) and, additionally, discrete (iii). We
      test whether one can use the Gaussian approximation of the FCS autocorrelation
      function to interpret the non-Gaussian data. We show that (i-iii) have
      approximately the same mean square displacements. Using simulations, we show that
      the FCS data suspected of restricted diffusion can be reliably interpreted using
      one archetypal model (i). Even if the underlying mechanism of the restriction is
      different or unknown, the accuracy of fitting the confinement size is excellent,
      and diffusion coefficients are also estimated with a good accuracy. This study
      gives a physical insight into the statistical behavior of different types of
      restricted diffusion and into the ability of fluorescence correlation
      spectroscopy to distinguish between them. 

PMID- 24738621
TI  - Multiple enzymatic digestions and ion mobility separation improve quantification
      of bacterial ribosomal proteins by data independent acquisition liquid
      chromatography-mass spectrometry.
AB  - Mass spectrometry-based quantification of ribosomal proteins (r-proteins)
      associated with mature ribosomes and ribosome assembly complexes is typically
      accomplished by relative quantification strategies. These strategies provide
      information on the relative stoichiometry of proteins within the complex compared
      to a wild-type strain. Here we have evaluated the applicability of a label-free
      approach, enhanced liquid chromatography-mass spectrometry (LC-MS(E)), for
      absolute "ribosome-centric" quantification of r-proteins in Escherichia coli
      mature ribosomes. Because the information obtained in this experiment is related
      to the number of peptides identified per protein, experimental conditions that
      allow accurate and reproducible quantification of r-proteins were found. Using an
      additional dimension of gas-phase separation through ion mobility and the use of
      multiple endoproteinase digestion significantly improved quantification of
      proteins associated with mature ribosomes. The actively translating ribosomes
      (polysomes) contain amounts of proteins consistent with their known stoichiometry
      within the complex. These measurements exhibited technical and biological
      reproducibilities at %CV less than 15% and 35%, respectively. The improved LC
      MS(E) approach described here can be used to characterize in vivo ribosome
      assembly complexes captured during ribosome biogenesis and assembly under
      different perturbations (e.g., antibiotics, deletion mutants of assembly factors,
      oxidative stress, nutrient deprivation). Quantitative analysis of these captured
      complexes will provide information relating to the interplay and dynamics of how
      these perturbations interfere with the assembly process. 

PMID- 24738622
TI  - Isoprene production in transgenic tobacco alters isoprenoid, non-structural
      carbohydrate and phenylpropanoid metabolism, and protects photosynthesis from
      drought stress.
AB  - Isoprene strengthens thylakoid membranes and scavenges stress-induced oxidative
      species. The idea that isoprene production might also influence isoprenoid and
      phenylpropanoid pathways under stress conditions was tested. We used transgenic
      tobacco to compare physiological and biochemical traits of isoprene-emitting (IE)
      and non-emitting (NE) plants exposed to severe drought and subsequent re
      watering. Photosynthesis was less affected by drought in IE than in NE plants,
      and higher rates were also observed in IE than in NE plants recovering from
      drought. Isoprene emission was stimulated by mild drought. Under severe drought,
      isoprene emission declined, and levels of non-volatile isoprenoids, specifically
      de-epoxidated xanthophylls and abscisic acid (ABA), were higher in IE than in NE
      plants. Soluble sugars and phenylpropanoids were also higher in IE plants. After
      re-watering, IE plants maintained higher levels of metabolites, but isoprene
      emission was again higher than in unstressed plants. We suggest that isoprene
      production in transgenic tobacco triggered different responses, depending upon
      drought severity. Under drought, the observed trade-off between isoprene and non
      volatile isoprenoids suggests that in IE plants isoprene acts as a short-term
      protectant, whereas non-volatile isoprenoids protect against severe, long-term
      damage. After drought, it is suggested that the capacity to emit isoprene might
      up-regulate production of non-volatile isoprenoids and phenylpropanoids, which
      may further protect IE leaves. 

PMID- 24738623
TI  - Tzanck smear for quick screening of transient myeloproliferative disorder in
      neonates with vesiculopapular eruptions.

PMID- 24738624
TI  - Establishment of reproducible, critical-sized, femoral segmental bone defects in
      rats.
AB  - Development of new treatment methodologies for bone nonunion requires validated
      experimental models for their application into tissue engineering approaches.
      Critical-sized bone defect (CSBD) models identify the smallest size at which
      tissue defects fail to completely heal during the experimental period. The
      purpose of this study was to systematically determine a CSBD in rat femurs using
      external fixation. Thirty Fischer 344 rats were equally divided into six groups.
      Bone defects of 1, 2, 3, 4, 5, and 6 mm were created in the diaphysis of the
      femur, before external fixation. Defects were evaluated radiographically at
      weekly intervals and histologically at the predefined healing period of 8 weeks.
      Defects of 4 mm or more failed to achieve union in our model. Nonunions were
      characterized by the absence of a bridging callus and filling of the defect with
      fibrous and muscle tissue. Radiographically, bone ends in nonunions were rounded
      up to 4 weeks postsurgery. Our systematic approach for identification of a CSBD
      in rat femurs, revealed that externally fixed defects of 4 mm and larger, failed
      to heal within the 8-week time frame.

PMID- 24738625
TI  - Pediatric idiopathic hypereosinophilic syndrome with Gianotti-Crosti syndrome: a
      novel presentation.

PMID- 24738626
TI  - Rational design of "heat seeking" drug loaded polypeptide nanoparticles that
      thermally target solid tumors.
AB  - This paper demonstrates the first example of targeting a solid tumor that is
      externally heated to 42  degrees C by "heat seeking" drug-loaded polypeptide
      nanoparticles. These nanoparticles consist of a thermally responsive elastin-like
      polypeptide (ELP) conjugated to multiple copies of a hydrophobic cancer drug. To
      rationally design drug-loaded nanoparticles that exhibit thermal responsiveness
      in the narrow temperature range between 37 and 42  degrees C, an analytical model
      was developed that relates ELP composition and chain length to the nanoparticle
      phase transition temperature. Suitable candidates were designed based on the
      predictions of the model and tested in vivo by intravital confocal fluorescence
      microscopy of solid tumors, which revealed that the nanoparticles aggregate in
      the vasculature of tumors heated to 42  degrees C and that the aggregation is
      reversible as the temperature reverts to 37  degrees C. Biodistribution studies
      showed that the most effective strategy to target the nanoparticles to tumors is
      to thermally cycle the tumors between 37 and 42  degrees C. These nanoparticles
      set the stage for the targeted delivery of a range of cancer chemotherapeutics by
      externally applied mild hyperthermia of solid tumors. 

PMID- 24738627
TI  - Comprehensive cryotherapy for recurrent breast cancer with distant metastases
      after failure of radical surgery.

PMID- 24738628
TI  - Thiophene-fused borepins as directly functionalizable boron-containing pi
      electron systems.
AB  - Synthetic protocols were developed for the gram-scale preparation of two isomeric
      dithienoborepins (DTBs), boron-containing polycyclic aromatics featuring the
      fusion of borepin and thiophene rings. DTBs exhibit reversible cathodic
      electrochemistry and boron-centered Lewis acidity in addition to enhanced
      electronic delocalization relative to benzo-fused analogues. Boron's precise
      position within the conjugation pathway of DTBs significantly affected electronic
      structure, most clearly demonstrated by the variation in spectroscopic responses
      of each isomer to fluoride ion binding. In addition to excellent stability in the
      presence of air and moisture, DTBs could also be subjected to electrophilic
      aromatic substitution and metalation chemistry, the latter enabling the direct,
      regiospecific functionalization of the unsubstituted thiophene rings. Subsequent
      tuning of molecular properties was achieved through installation of donor and
      acceptor pi-substituents, leading to compounds featuring multistep
      electrochemical reductions and polarizable electronic structures. As rare
      examples of directly functionalizable, pi-conjugated, boron-containing polycyclic
      aromatics, DTBs are promising building blocks for the next generation of
      organoboron pi-electron materials whose development will demand broad scope for
      molecular diversification in addition to chemical robustness. 

PMID- 24738629
TI  - Idarubicin-loaded beads for chemoembolisation of hepatocellular carcinoma:
      results of the IDASPHERE phase I trial.
AB  - BACKGROUND: A phase I dose-escalation trial of transarterial chemoembolisation
      (TACE) with idarubicin-loaded beads was performed in cirrhotic patients with
      hepatocellular carcinoma (HCC). AIM: To estimate the maximum-tolerated dose (MTD)
      and to assess safety, efficacy, pharmacokinetics and quality of life. METHODS:
      Patients received a single TACE session with injection of 2 mL drug-eluting beads
      (DEBs; DC Bead 300-500 MUm) loaded with idarubicin. The idarubicin dose was
      escalated according to a modified continuous reassessment method. MTD was defined
      as the dose level closest to that causing dose-limiting toxicity (DLT) in 20% of
      patients. RESULTS: Twenty-one patients were enrolled, including nine patients at
      5 mg, six patients at 10 mg, and six patients at 15 mg. One patient at each dose
      level experienced DLT (acute myocardial infarction, hyperbilirubinaemia and
      elevated aspartate aminotransferase (AST) at 5-, 10- and 15-mg, respectively).
      The calculated MTD of idarubicin was 10 mg. The most frequent grade >=3 adverse
      events were pain, elevated AST, elevated gamma-glutamyltranspeptidase and
      thrombocytopenia. At 2 months, the objective response rate was 52% (complete
      response, 28%, and partial response, 24%) by modified Response Evaluation
      Criteria in Solid Tumours. The median time to progression was 12.1 months (95% CI
      7.4 months--not reached); the median overall survival was 24.5 months (95% CI
      14.7 months--not reached). Pharmacokinetic analysis demonstrated the ability of
      DEBs to release idarubicin slowly. CONCLUSIONS: Using drug-eluting beads, the
      maximum-tolerated dose of idarubicin was 10 mg per TACE session. Encouraging
      responses and median time to progression were observed. Further clinical
      investigations are warranted (NCT01040559).

PMID- 24738630
TI  - Epilepsy treatment by sacrificing vitamin D.
AB  - Epilepsy is one of the most common neurologic disorders in childhood that often
      requires long term treatment with antiepileptic drugs. Both antiepileptic
      treatment and the comorbidities associated with epilepsy have a negative impact
      on bone health in growing children. Given the fact that vitamin D deficiency is a
      major public health problem worldwide, clinicians caring for children with
      chronic diseases should be aware of effects of the medication on the bone
      metabolism. Yet, vitamin D deficiency due to antiepileptic treatment is an
      overlooked issue among neurologists. In this review, we briefly describe vitamin
      D metabolism and the effect of vitamin D in the brain. We also discuss the
      literature in terms of vitamin D deficiency and antiepileptic treatment in the
      pediatric population.

PMID- 24738631
TI  - No more 'standard' abdominoperineal excision.

PMID- 24738632
TI  - Papillary glioneuronal tumor with a high proliferative component and
      minigemistocytes in a child.
AB  - Papillary glioneuronal tumor (PGNT) is a rare type of primary brain tumor.
      Although PGNT has traditionally been defined as a clinically indolent neoplasm,
      several cases with high proliferative activity and tumor recurrence have recently
      been reported. We report a case of PGNT in a 12-year-old boy who presented with
      epilepsy and harbored a 64 mm cystic tumor with a high proliferative component in
      the right temporal lobe. (11) C-methionine positron emission tomography (PET)
      showed high uptake in the solid mass. Gross total resection of the tumor mass was
      achieved and the patient became seizure-free without any neurological deficits.
      Histologically, the tumor contained two distinct areas of a vasocentric
      papilliform structure and a desmoplastic component. Minigemistocytic cells and
      small necrotic regions were observed adjacent to the pseudopapillae.
      Immunohistochemical analyses revealed both glial and neuronal differentiation.
      The Ki-67 proliferation index was high (14%) in the area corresponding to the
      high uptake region in the (11) C-methionine PET. No tumor recurrence was observed
      20 months after surgery. High proliferative PGNTs are rare and to our knowledge
      this is only the third pediatric case of PGNT with atypical features reported in
      the literature. Hence, we here review the reported cases of PGNT and discuss the
      clinical, radiological and histological features of this malignancy.

PMID- 24738639
TI  - Energy and motion: AMP-activated protein kinase alpha1 and its role in platelet
      activation.

PMID- 24738640
TI  - Emergence of Zaire Ebola virus disease in Guinea.
AB  - In March 2014, the World Health Organization was notified of an outbreak of a
      communicable disease characterized by fever, severe diarrhea, vomiting, and a
      high fatality rate in Guinea. Virologic investigation identified Zaire ebolavirus
      (EBOV) as the causative agent. Full-length genome sequencing and phylogenetic
      analysis showed that EBOV from Guinea forms a separate clade in relationship to
      the known EBOV strains from the Democratic Republic of Congo and Gabon.
      Epidemiologic investigation linked the laboratory-confirmed cases with the
      presumed first fatality of the outbreak in December 2013. This study demonstrates
      the emergence of a new EBOV strain in Guinea. 

PMID- 24738641
TI  - Abolishing mammography screening programs? A view from the Swiss Medical Board.

PMID- 24738642
TI  - Regulatory mandates for sepsis care--reasons for caution.

PMID- 24738643
TI  - Tetrandrine and caffeine modulated cell cycle and increased glioma cell death via
      caspase-dependent and caspase-independent apoptosis pathways.
AB  - Viability, cell cycle distribution, and expressions of eukaryotic translation
      initiation factor-2alpha (eIF-2alpha), cyclin D1, poly(ADP-ribose) polymerase 1
      (PARP-1), and apoptosis-inducing factor (AIF) of RT-2 glioma cells were assayed
      under treatment of tetrandrine and caffeine for 48 h. The results showed that
      cell viability decreased significantly under treatment with tetrandrine (5 MUM)
      alone or under combined treatment with tetrandrine (5 MUM) and caffeine (0.5 or 1
      mM). The ratio of RT-2 cells at sub G1 and G0/G1 stages increased significantly
      during combined treatment of tetrandrine (5 MUM) and caffeine (0.5, 1 mM). The
      ratio of phospharylated eIF-2alpha to dephospharylated eIF-2alpha increased,
      whereas cyclin D1 decreased significantly under combined treatment of tetrandrine
      (5 MUM) and caffeine (1 mM). The cleaved PARP-1 to PARP-1 ratio was elevated
      significantly under treatment of 5 MUM tetrandrine alone, and combined treatment
      of 5 MUM tetrandrine and caffeine (0.5, 1 mM). The expression levels of AIF
      increased significantly under treatment of 5 MUM tetrandrine alone or 1 mM
      caffeine alone, and combined treatment of 5 MUM tetrandrine and caffeine (0.5, 1
      mM). In conclusion, tetrandrine and caffeine could induce glioma cell death
      possibly via increasing eIF-2alpha phospharylation, decreasing cyclin-D1
      expression, and increasing caspase-dependent and -independent apoptosis pathways.

PMID- 24738644
TI  - Weekly risk of venous thromboembolism recurrence in patients receiving oral
      anticoagulants.
AB  - BACKGROUND: Data is currently lacking in evaluating the weekly rates of recurrent
      venous thromboembolism (VTE) among patients receiving anticoagulants. OBJECTIVE:
      To quantify the risk of VTE recurrence during the first 12 weeks after an index
      VTE event. METHODS: Healthcare claims from Truven Health Analytics MarketScan
      database from January 2007 to June 2012 were analyzed. Adult patients with >=1
      diagnosis of VTE, >=1 anticoagulant prescription dispensed within 7 days of the
      index VTE hospitalization discharge or outpatient/emergency room (ER) visit
      (index date), and a proportion of days covered >=0.7 on the anticoagulant therapy
      during the 12 weeks post-discharge were included. The weekly risk of VTE
      recurrence was evaluated with the hazard function using the life-table method.
      RESULTS: A total of 105,682 patients with a VTE were included. Mean age was 59
      years and 49% were female. The risk of VTE recurrence was at its highest during
      the first and second weeks, at 0.78% and 0.83%, respectively. The risk remained
      high during Weeks 3, 4, and 5 with risks of VTE recurrence of 0.63%, 0.52%, and
      0.39%, respectively. The risk of VTE recurrence stabilized around Week 7, with
      risks of 0.26%, 0.22%, 0.20%, 0.25%, 0.23%, and 0.23% for Weeks 7, 8, 9, 10, 11
      and 12, respectively. LIMITATIONS: Claims data may have contained inaccuracies.
      During hospitalizations it was not possible to assess anticoagulant use or a VTE
      recurrence occurring in the same hospitalization as the index VTE event.
      CONCLUSION: This analysis suggests that the risk of VTE recurrence remains high
      in the early weeks after an index VTE among patients receiving anticoagulants.

PMID- 24738645
TI  - Four Arabidopsis AREB/ABF transcription factors function predominantly in gene
      expression downstream of SnRK2 kinases in abscisic acid signalling in response to
      osmotic stress.
AB  - Under osmotic stress conditions such as drought and high salinity, the plant
      hormone abscisic acid (ABA) plays important roles in stress-responsive gene
      expression mainly through three bZIP transcription factors, AREB1/ABF2,
      AREB2/ABF4 and ABF3, which are activated by SNF1-related kinase 2s (SnRK2s) such
      as SRK2D/SnRK2.2, SRK2E/SnRK2.6 and SRK2I/SnRK2.3 (SRK2D/E/I). However, since the
      three AREB/ABFs are crucial, but not exclusive, for the SnRK2-mediated gene
      expression, transcriptional pathways governed by SRK2D/E/I are not fully
      understood. Here, we show that a bZIP transcription factor, ABF1, is a functional
      homolog of AREB1, AREB2 and ABF3 in ABA-dependent gene expression in Arabidopsis.
      Despite lower expression levels of ABF1 than those of the three AREB/ABFs, the
      areb1 areb2 abf3 abf1 mutant plants displayed increased sensitivity to drought
      and decreased sensitivity to ABA in primary root growth compared with the areb1
      areb2 abf3 mutant. Genome-wide transcriptome analyses revealed that expression of
      downstream genes of SRK2D/E/I, which include many genes functioning in osmotic
      stress responses and tolerance such as transcription factors and LEA proteins,
      was mostly impaired in the quadruple mutant. Thus, these results indicate that
      the four AREB/ABFs are the predominant transcription factors downstream of
      SRK2D/E/I in ABA signalling in response to osmotic stress during vegetative
      growth. 

PMID- 24738647
TI  - Chemometrics applied to quantitative analysis of ternary mixtures by terahertz
      spectroscopy.
AB  - Chemometrics was applied to qualitative and quantitative analyses of terahertz
      spectra obtained in transmission mode. A series of mixtures of three pure
      analytes, namely, citric acid, D-(-)fructose, and alpha-lactose monohydrate under
      various concentrations, was prepared as pressed pellets with polyethylene as
      binder. Then, terahertz absorbance spectra were recorded by terahertz time domain
      spectroscopy and analyzed. First, principal component analysis allowed one to
      correctly locate the samples into a ternary diagram. Second, quantitative
      analysis was achieved by partial least-squares (PLS) regression and artificial
      neural networks (ANN). The concentrations were predicted with values of relative
      mean square error lower than 0.9% for the three constituents. As a conclusion,
      chemometrics was demonstrated to be very efficient for the analysis of the
      ternary mixtures prepared for this study.

PMID- 24738646
TI  - The HLA-net GENE[RATE] pipeline for effective HLA data analysis and its
      application to 145 population samples from Europe and neighbouring areas.
AB  - In this review, we present for the first time an integrated version of the
      Gene[rate] computer tools which have been developed during the last 5 years to
      analyse human leukocyte antigen (HLA) data in human populations, as well as the
      results of their application to a large dataset of 145 HLA-typed population
      samples from Europe and its two neighbouring areas, North Africa and West Asia,
      now forming part of the Gene[va] database. All these computer tools and genetic
      data are, from now, publicly available through a newly designed bioinformatics
      platform, HLA-net, here presented as a main achievement of the HLA-NET scientific
      programme. The Gene[rate] pipeline offers user-friendly computer tools to
      estimate allele and haplotype frequencies, to test Hardy-Weinberg equilibrium
      (HWE), selective neutrality and linkage disequilibrium, to recode HLA data, to
      convert file formats, to display population frequencies of chosen alleles and
      haplotypes in selected geographic regions, and to perform genetic comparisons
      among chosen sets of population samples, including new data provided by the user.
      Both numerical and graphical outputs are generated, the latter being highly
      explicit and of publication quality. All these analyses can be performed on the
      pipeline after scrupulous validation of the population sample's characterisation
      and HLA typing reporting according to HLA-NET recommendations. The Gene[va]
      database offers direct access to the HLA-A, -B, -C, -DQA1, -DQB1, -DRB1 and -DPB1
      frequencies and summary statistics of 145 population samples having successfully
      passed these HLA-NET 'filters', and representing three European subregions (South
      East, North-East and Central-West Europe) and two neighbouring areas (North
      Africa, as far as Sudan, and West Asia, as far as South India). The analysis of
      these data, summarized in this review, shows a substantial genetic variation at
      the regional level in this continental area. These results have main implications
      for population genetics, transplantation and epidemiological studies. 

PMID- 24738648
TI  - Effects of Thai traditional massage on pressure pain threshold and headache
      intensity in patients with chronic tension-type and migraine headaches.
AB  - OBJECTIVE: To investigate the effects of Thai traditional massage (TTM) on
      pressure pain threshold (PPT) and headache intensity in patients with chronic
      tension-type and migraine headaches. DESIGN: Randomized controlled trial of TTM
      compared with the sham ultrasound (nine sessions each) during a 3-week period.
      PARTICIPANTS: Seventy-two participants who had had a headache diagnosis for at
      least 3 months before the experiment was recruited. RESULTS: After the treatment
      and at 3 and 9 weeks of follow-up, the TTM group showed a significant increase in
      PPT (p<0.01) compared with the sham ultrasound group. PPT values at baseline,
      after 3 weeks of treatment, and at 3- and 9-week follow-up for the TTM group were
      2.71 +/- 1.22, 3.57 +/- 1.41, 3.72 +/- 1.46, and 3.42 +/- 1.46 pounds/cm(2),
      respectively; values in the sham ultrasound group were 2.85 +/- 1.20, 2.62 +/-
      1.07, 2.58 +/- 1.05 and 2.63 +/- 0.94 pounds/cm(2). In both groups, headache
      intensity decreased significantly (p<0.05) at every end point of the outcome
      measures, and there were no differences between the groups (p>0.05). CONCLUSIONS:
      TTM could increase PPT and reduce headache intensity, suggesting that this is a
      possible alternative treatment for chronic headaches.

PMID- 24738649
TI  - Nodular cutaneous mucinosis associated with systemic lupus erythematosus.

PMID- 24738650
TI  - Stabilization of cucurbituril/guest assemblies via long-range Coulombic and
      CH...O interactions.
AB  - Cucurbit[n]urils (CB[n], n = 6-8) interact strongly with metal-bound 4'
      substituted terpyridine ligands (M = Fe(II) and Ir(III)) via CH...O hydrogen
      bonding, despite significant separation between the positive metallic cation and
      the carbonylated rim of CB[n], and the location of the latter in the second
      coordination sphere of the metal ion. While water has been shown to mediate
      interactions between cations and CB[n]s in some assemblies, mediation by organic
      ligands is unprecedented. The recognition process is driven by the contrasted
      combination of extremely favorable binding enthalpies (up to 20.2 kcal/mol) and
      very unfavorable entropic components (as low as -10.2 kcal/mol). Dynamic
      oligomers were prepared in the presence of CB[8], which acts as a "soft",
      noncovalent linker between metal/terpyridine complexes, and interconnects two 4'
      substituents inside its cavity. Social self-sorting between CB[8] and
      metal/terpyridine complexes bearing 4'-(2-naphthyl) and 4'-(2,3,5,6
      tetrafluorophenyl) substituents was also observed, and could afford well
      organized oligomers with alternating Fe(II) and Ir(III) cations. 

PMID- 24738651
TI  - Systematic review: The safety and efficacy of hyperbaric oxygen therapy for
      inflammatory bowel disease.
AB  - BACKGROUND: Hyperbaric oxygen therapy (HBOT) provides 100% oxygen under pressure,
      which increases tissue oxygen levels, relieves hypoxia and alters inflammatory
      pathways. Although there is experience using HBOT in Crohn's disease and
      ulcerative colitis, the safety and overall efficacy of HBOT in inflammatory bowel
      disease (IBD) is unknown. AIM: To quantify the safety and efficacy of HBOT for
      Crohn's disease (CD) and ulcerative colitis (UC). The rate of adverse events with
      HBOT for IBD was compared to the expected rate of adverse events with HBOT.
      METHODS: MEDLINE, EMBASE, Cochrane Collaboration and Web of Knowledge were
      systematically searched using the PRISMA standards for systematic reviews.
      Seventeen studies involving 613 patients (286 CD, 327 UC) were included. RESULTS:
      The overall response rate was 86% (85% CD, 88% UC). The overall response rate for
      perineal CD was 88% (18/40 complete healing, 17/40 partial healing). Of the 40 UC
      patients with endoscopic follow-up reported, the overall response rate to HBOT
      was 100%. During the 8924 treatments, there were a total of nine adverse events,
      six of which were serious. The rate of adverse events with HBOT in IBD is lower
      than that seen when utilising HBOT for other indications (P < 0.01). The risk of
      bias across studies was high. CONCLUSIONS: Hyperbaric oxygen therapy is a
      relatively safe and potentially efficacious treatment option for IBD patients. To
      understand the true benefit of HBOT in IBD, well-controlled, blinded, randomised
      trials are needed for both Crohn's disease and ulcerative colitis.

PMID- 24738652
TI  - Vernakalant for the conversion of atrial fibrillation: the new kid on the block?
AB  - Conversion of recent onset atrial fibrillation (AF) to sinus rhythm with
      antiarrhythmic drugs reduces the risk of hemodynamic instability,
      hospitalizations, and atrial remodeling seen with persistent AF. This is the main
      reason for pharmacological or electrical cardioversion to be considered first
      line of treatment for recent onset AF. Is there a role for new antiarrhythmic
      drugs in the conversion of AF as the first approach to a rhythm-control strategy?
      Vernakalant is a novel and relativity atrial selective drug which inhibits atrial
      selective K(+) currents, with only a small inhibitory effect on the rapidly
      activating delayed rectifier K(+) current (IKr) in the ventricle. In this brief
      Review, we tell the journey of vernakalant to become an attractive alternative to
      achieve pharmacological cardioversion of AF. 

PMID- 24738653
TI  - Drug reaction with eosinophilia and systemic symptoms: manifestations, treatment,
      and outcome in 17 patients.
AB  - BACKGROUND: Drug-induced hypersensitivity syndrome (DIHS) or drug reaction with
      eosinophilia and systemic symptoms (DRESS) is a rare type of adverse drug
      reaction with complex clinical features involving multiple systems of the body.
      OBJECTIVES: This study was designed to evaluate the clinical features, course,
      response to treatment, and outcome of DRESS. METHODS: The study involved a
      retrospective analysis of data collected over a period of four years in 17
      patients with DRESS. Clinical features, laboratory findings, responses to
      treatment, and outcomes were investigated. RESULTS: The study population included
      17 patients, of whom eight (47.1%) were male and nine (52.9%) were female. The
      most common (64.7%) culprit drugs were anticonvulsants (phenytoin,
      phenobarbitone, carbamazepine, oxcarbazepine, and lamotrigine). Other causative
      drugs included allopurinol, dapsone, vancomycin, leflunomide, and nitrofurantoin.
      The latency period varied from 11 days to 34 days, with a mean of 22.35 +/- 5.83
      days. The mean latency period of anticonvulsant drugs was longer than that of
      other drugs. Multisystem involvement was present in all patients. Systemic
      corticosteroids, injectable followed by oral, were administered to all patients.
      Thirteen (76.5%) patients recovered completely, two (11.7%) developed post
      inflammatory hyperpigmentation, and one (5.9%) patient developed renal failure.
      One patient with liver failure had a poor outcome. CONCLUSIONS: A variety of
      drugs can cause DRESS, the most common being anticonvulsants. Patients show
      diverse presentations with varied organ involvement. Systemic corticosteroids are
      an effective management option and are associated with a good clinical outcome if
      started early.

PMID- 24738654
TI  - Epilepsy in women with gynecologic malignancies.
AB  - Women with gynecologic malignancies are a population with various risk factors
      for epilepsy. Gynecologic malignancies can substantially affect daily life, even
      if the tumor is well controlled. Gynecologic malignancies may cause brain
      metastasis, paraneoplastic neurological disorders, or leptomeningeal
      carcinomatosis, which potentially directly cause seizures and epilepsy. Moreover,
      metabolic disorders, central nervous system infections, cerebrovascular
      complications, and chemotherapeutic drugs can indirectly induce ictus.
      Radiotherapy of brain metastases can also lead to seizure and epilepsy.
      Understanding these pathogenic mechanisms may provide novel viewpoints or methods
      for diagnosis, prevention and treatment of epilepsy associated with gynecologic
      malignancies. In this article, we extensively review the related literature
      regarding potential aetiologies, their mechanisms, clinical features, diagnosis
      and treatment.

PMID- 24738655
TI  - Biocompatible polymeric microparticles produced by a simple biomimetic approach.
AB  - The use of superhydrophobic surfaces to produce polymeric particles proves to be
      biologically friendly since it entails the pipetting and subsequent cross-linking
      of polymeric solutions under mild experimental conditions. Moreover, it renders
      encapsulation efficiencies of ~100%. However, the obtained particles are 1 to 2
      mm in size, hindering to a large extent their application in clinical trials.
      Improving on this technique, we propose the fabrication of polymeric
      microparticles by spraying a hydrogel precursor over superhydrophobic surfaces
      followed by photo-cross-linking. The particles were produced from methacrylamide
      chitosan (MA-CH) and characterized in terms of their size and morphology. As
      demonstrated by optical and fluorescence microscopy, spraying followed by photo
      cross-linking led, for the first time, to the production of spherical particles
      with diameters on the order of micrometers, nominal sizes not attainable by
      pipetting. Particles such as these are suitable for medical applications such as
      drug delivery and tissue engineering. 

PMID- 24738656
TI  - Thermal conductivity of mechanically joined semiconducting/metal nanomembrane
      superlattices.
AB  - The decrease of thermal conductivity is crucial for the development of efficient
      thermal energy converters. Systems composed of a periodic set of very thin layers
      show among the smallest thermal conductivities reported to-date. Here, we
      fabricate in an unconventional but straightforward way hybrid superlattices
      consisting of a large number of nanomembranes mechanically stacked on top of each
      other. The superlattices can consist of an arbitrary composition of n- or p-type
      doped single-crystalline semiconductors and a polycrystalline metal layer. These
      hybrid multilayered systems are fabricated by taking advantage of the self
      rolling technique. First, differentially strained nanomembranes are rolled into
      three-dimensional microtubes with multiple windings. By applying vertical
      pressure, the tubes are then compressed and converted into a planar hybrid
      superlattice. The thermal measurements show a substantial reduction of the cross
      sectional heat transport through the nanomembrane superlattice compared to a
      single nanomembrane layer. Time-domain thermoreflectance measurements yield
      thermal conductivity values below 2 W m(-1) K(-1). Compared to bulk values, this
      represents a reduction of 2 orders of magnitude by the incorporation of the
      mechanically joined interfaces. The scanning thermal atomic force microscopy
      measurements support the observation of reduced thermal transport on top of the
      superlattices. In addition, small defects with a spatial resolution of ~100 nm
      can be resolved in the thermal maps. The low thermal conductivity reveals the
      potential of this approach to fabricate miniaturized on-chip solutions for energy
      harvesters in, e.g., microautonomous systems. 

PMID- 24738657
TI  - Glucose- and nitrogen sensing and regulatory mechanisms in Saccharomyces
      cerevisiae.
AB  - Pro- and eukaryotic cells are constantly challenged by varying concentrations of
      nutrients in their environment. Perceiving and adapting to such changes are
      therefore crucial for cellular viability. Thus, numerous specialized cellular
      receptors continuously sense and react to the availability of nutrients such as
      glucose and nitrogen. When stimulated, these receptors initiate various cellular
      signaling pathways, which in concert constitute a complex regulatory network. To
      ensure a highly specific response, these pathways and networks cross-communicate
      with each other and are regulated at several steps and by numerous different
      regulators. As numerous of these regulating proteins, biochemical mechanisms, and
      cellular pathways are evolutionary conserved, complex biochemical information
      relevant to humans can be obtained by studying simple organisms. Thus, the yeast
      Saccharomyces cerevisiae has been recognized as a powerful model system to study
      fundamental biochemical processes. In the present review, we highlight central
      signaling pathways and molecular circuits conferring nitrogen- and glucose
      sensing in S. cerevisiae. 

PMID- 24738658
TI  - Signalling pathways involved in paracetamol-induced hepatotoxicity: new insights
      on the role of protein tyrosine phosphatase 1B.
AB  - Acute hepatic failure secondary to paracetamol poisoning is associated with high
      mortality. Paracetamol-induced hepatotoxicity causes oxidative stress that
      triggers signalling pathways and ultimately leads to lethal hepatocyte injury. We
      will review the signalling pathways activated by paracetamol in the liver
      emphasizing the role of protein tyrosine phosphatase 1B (PTP1B) in the balance
      between cell death and survival in hepatocytes. PTP1B has emerged as a key
      modulator of the antioxidant system mediated by the nuclear factor erythroid-2
      related factor 2 (Nrf2) in hepatic cells in response to paracetamol overdose.
      Also, this phosphatase modulates the classical survival pathways triggered by the
      activation of the insulin-like growth factor-I (IGF-I) signalling cascade.
      Therefore, PTP1B is a novel therapeutic target against paracetamol-induced liver
      failure.

PMID- 24738659
TI  - Multiple cerebral lesions in a 60-year-old female patient with a history of liver
      transplantation.

PMID- 24738660
TI  - Successful switch to rilpivirine/tenofovir/emtricitabine in HIV-1-infected
      patients with an isolated K103N mutation acquired during prior nonnucleoside
      reverse transcriptase inhibitor therapy.
AB  - OBJECTIVES: Whether treatment-experienced HIV-1-infected patients with an
      acquired K103N mutation after failing nonnucleoside reverse transcriptase
      inhibitor (NNRTI) regimens can be treated with rilpivirine is unknown. The aim of
      this pilot study was to evaluate the efficacy of
      rilpivirine/tenofovir/emtricitabine in HIV-1-infected patients with an isolated
      K103N mutation. METHODS: A prospective study was carried out in HIV-1-infected
      adults who acquired the K103N mutation on failing NNRTI regimens. No other
      mutations in reverse transcriptase were allowed. Patients had to be on second
      line regimens with HIV-1 RNA < 200 copies/mL for >= 6 months. Exclusion criteria
      were: use of acid-reducing agents, insufficient caloric intake and impaired renal
      function. Of primary interest was virological success (HIV-1 RNA < 200 copies/mL)
      at weeks 6, 12, 24 and 48. RESULTS: Of 1550 HIV-1-infected patients at the
      Erasmus Medical Center Rotterdam, we identified 10 HIV-1-infected patients with
      an isolated K103N mutation acquired after NNRTI failure. Five patients were not
      eligible for inclusion in the study, and two patients refused participation.
      Three African women (23-35 years of age) were included and were switched from
      boosted protease inhibitor-based second-line therapies to
      rilpvirine/tenofovir/emtricitabine. HIV-1 RNA was < 200 copies/mL at weeks 6, 12,
      24 and 48 for all patients. No adverse events were observed. All patients had HIV
      1 RNA < 200 copies/mL for 6-50 months prior to the switch. CONCLUSIONS: This
      pilot study demonstrates the successful switch of HIV-1-infected patients who
      acquired an isolated K103N mutation during previous NNRTI therapy to
      rilpivirine/tenofovir/emtricitabine. In selected patients, single-tablet regimens
      are also becoming a valid treatment option for second-line HIV-1 therapy.

PMID- 24738661
TI  - Does size of one's community affect likelihood of being drafted into the NHL?
      Analysis of 25 years of data.
AB  - The consistency of community size effects in North American contexts but not
      elsewhere, reinforces the notion that the effect is driven by socio-cultural
      factors specific to the country under examination. In order to identify and
      understand the various forces driving the community size effect, it is important
      to determine whether the effect has changed over time. Stability or instability
      over time would assist researchers in identifying the specific socio-cultural
      mechanisms driving these effects. This study compared the influence of community
      size on the likelihood of being drafted into the National Hockey League (NHL)
      among Canadian ice hockey players drafted to play in the NHL between 1985 and
      2009. Although there was some variability over the timespan examined, most
      notably in communities with between 250,000 and 499,999 inhabitants and over
      1,000,000 inhabitants, trends were generally stable over time, suggesting that
      the socio-cultural mechanisms may have also been relatively stable, although
      further work is necessary to confirm this assumption.

PMID- 24738662
TI  - Examination of metals from aerospace-related activity in surface water samples
      from sites surrounding the Kennedy Space Center (KSC), Florida.
AB  - Metal contamination from Space Shuttle launch activity was examined using
      inductively coupled plasma-atomic emission spectroscopy in a two-tier study
      sampling surface water collected from several sites at the Kennedy Space Center
      (KSC) and associated Merritt Island National Wildlife Refuge in east central
      Florida. The primary study examined both temporal changes in baseline metal
      concentrations (19 metals) in surface water (1996 to 2009, 11 sites) samples
      collected at specific long-term monitoring sites and metal deposition directly
      associated with Space Shuttle launch activity at two Launch Complexes (LC39A and
      LC39B). A secondary study examined metal concentrations at additional sites and
      increased the amount of elements measured to 48 elements. Our examination places
      a heavy focus on those metals commonly associated with launch operations (e.g.,
      Al, Fe, Mn, and Zn), but a brief discussion of other metals (As, Cu, Mo, Ni, and
      Pb) is also included. While no observable accumulation of metals occurred during
      the time period of the study, the data obtained postlaunch demonstrated a
      dramatic increase for Al, Fe, Mn, and Zn. Comparing overall trends between the
      primary and secondary baseline surface water concentrations, elevated
      concentrations were generally observed at sampling stations located near the
      launch complexes and from sites isolated from major water systems. While there
      could be several natural and anthropogenic sources for metal deposition at KSC,
      the data in this report indicate that shuttle launch events are a significant
      source. 

PMID- 24738663
TI  - Anti-asthmatic activities of an ethanol extract of Aster yomena in an ovalbumin
      induced murine asthma model.
AB  - Aster yomena is used in traditional remedies to treat cough, asthma and insect
      bites; however, its therapeutic mechanism is not completely understood. To
      elucidate the anti-asthmatic effect of A. yomena, we investigated the anti
      asthmatic characteristics of an alcohol extract of A. yomena in an ovalbumin
      (OVA)-induced murine asthma model. In this study, we showed that A. yomena
      extract inhibited the overall pathophysiological features of asthma by
      suppressing Th2 responses and enzymes associated with the production of
      inflammatory mediators. This suppression resulted in decreased Th2 type cytokines
      and eosinophils in the bronchoalveolar lavage fluid and OVA-specific IgE in
      serum. Additionally, A. yomena extract significantly decreased airway
      hyperresponsiveness and abrogated the histopathological changes in the lungs,
      which reached normal levels in the OVA-challenged mice treated with A. yomena
      extract. These findings suggest that A. yomena could be a promising natural agent
      for treating bronchial asthma in humans.

PMID- 24738664
TI  - Simultaneous electropolymerization and electro-click functionalization for highly
      versatile surface platforms.
AB  - Simple preparation methods of chemically versatile and highly functionalizable
      surfaces remain rare and present a challenging research objective. Here, we
      demonstrate a simultaneous electropolymerization and electro-click
      functionalization process (SEEC) for one-pot self-construction of aniline- and
      naphthalene-based functional polymer films where both polymerization and click
      functionalization are triggered by applying electrochemical stimuli. Cyclic
      voltammetry (CV) can be applied for the simultaneous oxidation of 4-azidoaniline
      and the reduction of Cu(II) ions, resulting in polymerization of the former, and
      the Cu(I)-catalyzed alkyne/azide cycloaddition ("click" chemistry). Properties of
      the films obtained can be tuned by varying their morphology, their chemically
      "clicked" content, or by postconstruction functionalization. To demonstrate this,
      the CV scan rates, component monomers, and "clicked" molecules were varied.
      Covalent postconstruction immobilization of horseradish peroxidase was also
      performed. Consequently, pseudocapacitance and enzyme activity were affected.
      SEEC provides surface scientists an easy access to a wide range of
      functionalization possibilities in several fields including sensors, fuel cells,
      photovoltaics, and biomaterials. 

PMID- 24738665
TI  - ILEI: a novel marker for epithelial-mesenchymal transition and poor prognosis in
      colorectal cancer.
AB  - AIMS: Accumulating evidence over the past decade has shown that abnormal
      activation of epithelial to mesenchymal transition (EMT) contributes to tumour
      progression and metastasis in colorectal cancer (CRC). In this study, we
      investigated the expression of interleukin-like EMT inducer (ILEI) and EMT
      associated markers (E-cadherin, vimentin) in CRC tissues and determined the
      correlations between ILEI expression and clinicopathological characteristics,
      prognosis and EMT in CRC. METHODS AND RESULTS: In total, 194 patients diagnosed
      with CRC based on histopathological evaluation and those subjected to surgical
      resection at the First Hospital of China Medical University between 2003 and 2005
      were examined. Immunohistochemical staining for ILEI, vimentin and E-cadherin was
      performed for each specimen. Cytoplasmic overexpression of ILEI usually
      accompanied down-regulation of E-cadherin and positive expression of vimentin.
      Conversely, ILEI was simultaneously down-regulated with overexpression of E
      cadherin and negative expression of vimentin. ILEI overexpression was associated
      significantly with T-stage, N-stage, TNM stage and EMT phenotype (P = 0.024,
      <0.001, <0.001 and <0.001, respectively). Multivariate analysis revealed that
      ILEI expression was an independent prognostic factor for patient survival.
      CONCLUSIONS: Our findings indicate that cytoplasmic ILEI expression is a
      potential marker of EMT and tumour progression in CRC. ILEI is an independent
      predictive factor associated with poor prognosis in CRC.

PMID- 24738666
TI  - Using a drug-safety tool to prevent competition.

PMID- 24738667
TI  - Comparative effectiveness questions in oncology.

PMID- 24738668
TI  - Changes in diabetes-related complications in the United States, 1990-2010.
AB  - BACKGROUND: Preventive care for adults with diabetes has improved substantially
      in recent decades. We examined trends in the incidence of diabetes-related
      complications in the United States from 1990 through 2010. METHODS: We used data
      from the National Health Interview Survey, the National Hospital Discharge
      Survey, the U.S. Renal Data System, and the U.S. National Vital Statistics System
      to compare the incidences of lower-extremity amputation, end-stage renal disease,
      acute myocardial infarction, stroke, and death from hyperglycemic crisis between
      1990 and 2010, with age standardized to the U.S. population in the year 2000.
      RESULTS: Rates of all five complications declined between 1990 and 2010, with the
      largest relative declines in acute myocardial infarction (-67.8%; 95% confidence
      interval [CI], -76.2 to -59.3) and death from hyperglycemic crisis (-64.4%; 95%
      CI, -68.0 to -60.9), followed by stroke and amputations, which each declined by
      approximately half (-52.7% and -51.4%, respectively); the smallest decline was in
      end-stage renal disease (-28.3%; 95% CI, -34.6 to -21.6). The greatest absolute
      decline was in the number of cases of acute myocardial infarction (95.6 fewer
      cases per 10,000 persons; 95% CI, 76.6 to 114.6), and the smallest absolute
      decline was in the number of deaths from hyperglycemic crisis (-2.7; 95% CI, -2.4
      to -3.0). Rate reductions were larger among adults with diabetes than among
      adults without diabetes, leading to a reduction in the relative risk of
      complications associated with diabetes. When expressed as rates for the overall
      population, in which a change in prevalence also affects complication rates,
      there was a decline in rates of acute myocardial infarction and death from
      hyperglycemic crisis (2.7 and 0.1 fewer cases per 10,000, respectively) but not
      in rates of amputation, stroke, or end-stage renal disease. CONCLUSIONS: Rates of
      diabetes-related complications have declined substantially in the past two
      decades, but a large burden of disease persists because of the continued increase
      in the prevalence of diabetes. (Funded by the Centers for Disease Control and
      Prevention.).

PMID- 24738670
TI  - Acute infectious diarrhea in immunocompetent adults.

PMID- 24738669
TI  - Transferable vancomycin resistance in a community-associated MRSA lineage.
AB  - We report the case of a patient from Brazil with a bloodstream infection caused
      by a strain of methicillin-resistant Staphylococcus aureus (MRSA) that was
      susceptible to vancomycin (designated BR-VSSA) but that acquired the vanA gene
      cluster during antibiotic therapy and became resistant to vancomycin (designated
      BR-VRSA). Both strains belong to the sequence type (ST) 8 community-associated
      genetic lineage that carries the staphylococcal chromosomal cassette mec (SCCmec)
      type IVa and the S. aureus protein A gene (spa) type t292 and are
      phylogenetically related to MRSA lineage USA300. A conjugative plasmid of 55,706
      bp (pBRZ01) carrying the vanA cluster was identified and readily transferred to
      other staphylococci. The pBRZ01 plasmid harbors DNA sequences that are typical of
      the plasmid-associated replication genes rep24 or rep21 described in community
      associated MRSA strains from Australia (pWBG745). The presence and dissemination
      of community-associated MRSA containing vanA could become a serious public health
      concern. 

PMID- 24738671
TI  - Images in clinical medicine. Ear replantation.

PMID- 24738672
TI  - Case records of the Massachusetts General Hospital. Case 12-2014. A 59-year-old
      man with fatigue, abdominal pain, anemia, and abnormal liver function.

PMID- 24738673
TI  - Sticking with synthetic tissue sealants.

PMID- 24738674
TI  - Daclatasvir plus sofosbuvir for HCV infection.

PMID- 24738675
TI  - Daclatasvir plus sofosbuvir for HCV infection.

PMID- 24738676
TI  - Proteome-wide analysis and CXCL4 in systemic sclerosis.

PMID- 24738677
TI  - Proteome-wide analysis and CXCL4 in systemic sclerosis.

PMID- 24738678
TI  - Proteome-wide analysis and CXCL4 in systemic sclerosis.

PMID- 24738679
TI  - Proteome-wide analysis and CXCL4 in systemic sclerosis.

PMID- 24738680
TI  - Distracted driving and crash risk.

PMID- 24738681
TI  - Distracted driving and crash risk.

PMID- 24738682
TI  - Distracted driving and crash risk.

PMID- 24738683
TI  - Distracted driving and crash risk.

PMID- 24738684
TI  - Distracted driving and crash risk.

PMID- 24738685
TI  - Sedation and delirium in intensive care.

PMID- 24738686
TI  - Sedation and delirium in intensive care.

PMID- 24738687
TI  - Sedation and delirium in intensive care.

PMID- 24738688
TI  - The Arizona debacle--a physician's perspective.

PMID- 24738689
TI  - Tracheal allograft after withdrawal of immunosuppressive therapy.

PMID- 24738690
TI  - Images in clinical medicine. Occipital calcification and celiac disease.

PMID- 24738691
TI  - Identification of the novel HLA-C*03:240 allele.
AB  - HLA-C*03:240 differs from HLA-C*03:42 by a single nucleotide substitution that
      results in a missense mutation Tyr 99 Cys (TAT to TGT). 

PMID- 24738692
TI  - Mild and chemoselective lactone ring-opening with (TMS)ONa. Mechanistic studies
      and application to sweroside derivatives.
AB  - Mild and chemoselective opening of lactones with sodium trimethylsilanolate in
      high yields and aprotic solvents is described. Kinetic studies demonstrate that
      the B(Ac)2 mechanistic pathway is followed. Nucleophilic attack of silanolate
      onto the carbonyl of the lactone moiety is the rate-determining step. NaOH
      present as an impurity accelerates the reaction. The method was further applied
      to the base-sensitive and stable lactones derived from highly functionalized
      iridoid derivatives.

PMID- 24738693
TI  - Combined treatment with Epimedium koreanum Nakai extract and gefitinib overcomes
      drug resistance caused by T790M mutation in non-small cell lung cancer cells.
AB  - Although the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors,
      such as gefitinib, have shown promising therapeutic efficacy in nonsmall cell
      lung cancer (NSCLC) patients harboring EGFR activating mutation, development of
      acquired resistance is almost inevitable. We investigated whether the addition of
      Epimedium koreanum Nakai extract (EEF) to gefitinib could overcome the resistance
      of NSCLC cells to gefitinib. In our study, the growth inhibitory effects of
      cotreatment differed between mutant EGFR and wild type EGFR. A synergistic
      antiproliferative effect was observed in the combined treatments in H1975 and PC
      9GR cells carrying T790M EGFR. In addition, the cotreatment exhibited a much
      greater inhibition than either agent alone on the following metastatic processes:
      (a) invasion, (b) wound healing, and (c) tubule formation by endothelial cells.
      The phosphorylations of EGFR family (EGFR, HER-2, and HER-3) and EGFR downstream
      PI3K/Akt/mTOR pathway in H1975 and PC-9/GR cells were also attanuated, whereas
      EEF or gefitinib alone had no obvious effects. Similarly, the combination
      effectively suppressed tumor growth and increased mice survival in PC-9GR
      xenografts. The results indicate that the addition of EEF to gefitinib is a
      promising strategy to overcome T790M-mediated drug resistance. 

PMID- 24738694
TI  - Use of prescription opioids with abuse-deterrent technology to address opioid
      abuse.
AB  - OBJECTIVE: The development of new formulations of extended-release (ER) opioids
      with abuse-deterrent technology attempts to deter prescription opioid abuse while
      maintaining appropriate access to care for pain patients. This study examined the
      degree to which some patients may avoid switching to reformulated ER opioids with
      abuse-deterrent technology and the extent to which those patients are more likely
      to be abusers. RESEARCH DESIGN AND METHODS: We analyzed Truven MarketScan
      pharmacy and medical claims data following the introduction of two reformulated
      ER opioids with abuse-deterrent technology. Adults aged 18-64 who were continuous
      users of extended-release oxycodone HCl (ER oxycodone) or extended-release
      oxymorphone HCl (ER oxymorphone) in a 6 month period prior to the introduction of
      the respective reformulations of those products were identified and categorized
      based on whether they switched to the reformulation, switched to other ER/long
      acting (LA) opioids (without abuse-deterrent technology), or discontinued ER/LA
      opioid treatment in a 6 month post-reformulation period. Abusers were identified
      using ICD-9-CM diagnosis codes for opioid abuse/dependence. Pearson's chi-squared
      tests and Fisher's exact tests were then used to compare rates of abuse between
      patients who avoided switching to a reformulated ER opioid. Sensitivity analyses
      examined several definitions used in this analysis. MAIN OUTCOME MEASURES: ER/LA
      opioid utilization; rates of diagnosed opioid abuse. RESULTS: A total of 31%-50%
      of patients avoided switching to reformulated ER opioids. Rates of diagnosed
      opioid abuse were higher among these patients compared to patients who
      transitioned to the reformulated ER opioids. LIMITATIONS: Due to the
      observational research design, caution is warranted in causal interpretation of
      the findings. The study was conducted among commercially insured continuous ER
      oxycodone or ER oxymorphone users; future research should consider additional
      patient populations, such as non-continuous users and those without commercial
      insurance (i.e., Medicare, Medicaid, uninsured). CONCLUSIONS: Some patients
      switched to other ER/LA opioids without abuse-deterrent technology or
      discontinued ER/LA opioid treatment when their existing ER treatment was
      reformulated. Rates of opioid abuse were higher among patients who switched to
      other ER/LA opioids or discontinued ER/LA opioid treatment, suggesting that
      abusers may seek more easily abuseable alternatives such as prescription opioids
      without abuse-deterrent technology.

PMID- 24738695
TI  - Effect of the herbal combination Canephron N on diabetic nephropathy in patients
      with diabetes mellitus: results of a comparative cohort study.
AB  - OBJECTIVES: Diabetic nephropathy (DN) is a serious and common complication of
      diabetes mellitus leading to end-stage renal disease in up to 30% of diabetic
      patients. The first manifestation of DN in humans is microalbuminuria, which
      arises from the increased passage of albumin through the glomerular filtration
      barrier. Reactive oxygen species, inflammatory cytokines, and growth factors are
      key players in the context of damage to the glomerular filtration barrier.
      INTERVENTIONS: In this study the herbal combination Canephron((r)) N, containing
      lovage root, rosemary leaves, and centaury herb, was administered to patients
      with DN to study the effects on microalbuminuria and overall oxidant/antioxidant
      status. An open study involving 59 patients with DN was performed to compare the
      effects of Canephron N administered concomitantly with standard antidiabetic
      therapy and an angiotensin-converting enzyme (ACE) inhibitor, with the standard
      therapy and ACE inhibitor treatment alone. RESULTS: After 6 months of therapy the
      level of microalbuminuria decreased significantly in the study group compared
      with the control group. Canephron N had a positive effect on the antioxidant
      defense status and lipid peroxidation levels. In addition, liver aminotransferase
      levels did not change. CONCLUSIONS: With respect to the excellent tolerability,
      the study results encourage use of the herbal combination as an add-on therapy in
      patients with DN.

PMID- 24738696
TI  - Oligonaphthofurans: fan-shaped and three-dimensional pi-compounds.
AB  - Using a bottom-up method, we prepared a series of oligonaphthofurans composed of
      alternating naphthalene rings and furan rings. The largest compound (compound 25)
      contained 8 naphthalene units and 7 furan units. DFT calculations revealed that
      these compounds were fan-shaped molecules and each naphthalene ring was oriented
      in an alternate mountain-valley fold conformation because of steric repulsion by
      the hydrogens at the peri-positions. We investigated the optical properties that
      derived from their fan-shaped and mountain-valley sequences. As the number of
      aromatic rings of the oligonaphthofurans increased, the peaks of the longest
      wavelength absorptions in the UV-vis spectra (HOMO-LUMO energy gap) of these
      compounds steadily red-shifted, although the shapes of spectra were not sustained
      because of the decreasing molar absorption coefficients (epsilon's) of their
      lambda(max). We compared our results with those reported for other types of
      oligoaromatic compounds such as acenes 1, ethene-bridged p-phenylenes 2, rylenes
      3, oligofurans 4, and oligonaphthalenes 5. The slopes of the plots between the
      transition energies (HOMO-LUMO energy gap) of the oligoaromatic compounds and the
      reciprocal of the number of aromatic rings indicated that the efficiency of pi
      conjugation of the oligonaphthofurans was comparable with that of linear and
      rigid acenes and rylenes. The higher-order compounds 22 and 25 aggregated even
      under high dilution conditions (~10(-6) M).

PMID- 24738697
TI  - Plant volatiles in polluted atmospheres: stress responses and signal degradation.
AB  - Plants emit a plethora of volatile organic compounds, which provide detailed
      information on the physiological condition of emitters. Volatiles induced by
      herbivore feeding are among the best studied plant responses to stress and may
      constitute an informative message to the surrounding community and further
      function in plant defence processes. However, under natural conditions, plants
      are potentially exposed to multiple concurrent stresses with complex effects on
      the volatile emissions. Atmospheric pollutants are an important facet of the
      abiotic environment and can impinge on a plant's volatile-mediated defences in
      multiple ways at multiple temporal scales. They can exert changes in volatile
      emissions through oxidative stress, as is the case with ozone pollution. The
      pollutants, in particular, ozone, nitrogen oxides and hydroxyl radicals, also
      react with volatiles in the atmosphere. These reactions result in volatile
      breakdown products, which may themselves be perceived by community members as
      informative signals. In this review, we demonstrate the complex interplay among
      stresses, emitted signals, and modification in signal strength and composition by
      the atmosphere, collectively determining the responses of the biotic community to
      elicited signals. 

PMID- 24738699
TI  - Primary cutaneous CD30-positive anaplastic large cell lymphoma in an 80-year-old
      man: a case report from Nepal.

PMID- 24738698
TI  - Discovery and characterization of a photo-oxidative histidine-histidine cross
      link in IgG1 antibody utilizing 18O-labeling and mass spectrometry.
AB  - A novel photo-oxidative cross-linking between two histidines (His-His) has been
      discovered and characterized in an IgG1 antibody via the workflow of XChem
      Finder, (18)O labeling and mass spectrometry (Anal. Chem. 2013, 85, 5900-5908).
      Its structure was elucidated by peptide mapping with multiple proteases with
      various specificities (e.g., trypsin, Asp-N, and GluC combined with trypsin or
      Asp-N) and mass spectrometry with complementary fragmentation modes (e.g.,
      collision-induced dissociation (CID) and electron-transfer dissociation (ETD)).
      Our data indicated that cross-linking occurred across two identical conserved
      histidine residues on two separate heavy chains in the hinge region, which is
      highly flexible and solvent accessible. On the basis of model studies with short
      peptides, it has been proposed that singlet oxygen reacts with the histidyl
      imidazole ring to form an endoperoxide and then converted to the 2-oxo-histidine
      (2-oxo-His) and His+32 intermediates, the latter is subject to a nucleophilic
      attack by the unmodified histidine; and finally, elimination of a water molecule
      leads to the final adduct with a net mass increase of 14 Da. Our findings are
      consistent with this mechanism. Successful discovery of cross-linked His-His
      again demonstrates the broad applicability and utility of our XChem-Finder
      approach in the discovery and elucidation of protein cross-linking, particularly
      without a priori knowledge of the chemical nature and site of cross-linking.

PMID- 24738700
TI  - Norfolk QOL-DN: validation of a patient reported outcome measure in transthyretin
      familial amyloid polyneuropathy.
AB  - The Norfolk Quality of Life-Diabetic Neuropathy (QOL-DN) questionnaire is an
      instrument to assess QOL in diabetic polyneuropathy. The objective of this
      observational, cross-sectional study in 61 patients with V30M transthyretin
      familial amyloid polyneuropathy (TTR-FAP) and 16 healthy volunteers was to
      validate the Norfolk QOL-DN for assessment of QOL in TTR-FAP. Comparisons were
      conducted to identify the best items to discriminate disease stages and assess
      which individual Norfolk domains (symptoms, large fiber, small fiber, autonomic,
      and activities of daily living) would be most affected by disease stage. Analysis
      of individual items revealed a significant pattern of discrimination among
      disease stages (p < 0.001). Total QOL scores increased (indicating worsening)
      with duration of symptoms, with a steeper increase observed earlier in the course
      of disease. Significant correlations were observed between each Norfolk domain
      and other measures of neurological function. Limitations include cross-sectional
      study design, low patient numbers in this rare disease, and the ordinal-based
      character of the metric used; future areas to explore include item response
      theory approaches such as Rasch analysis. These results suggest the Norfolk QOL
      DN is a reliable indicator of the impact of disease severity on QOL in patients
      with TTR-FAP.

PMID- 24738701
TI  - Randomised clinical trial: The beneficial effects of VSL#3 in obese children with
      non-alcoholic steatohepatitis.
AB  - BACKGROUND: Gut microbiota modifiers may have beneficial effects of non-alcoholic
      fatty liver disease (NAFLD) but randomised controlled trials (RCT) are lacking in
      children. AIM: To perform a double-blind RCT of VSL#3 vs. placebo in obese
      children with biopsy-proven NAFLD. METHODS: Of 48 randomised children, 44 (22
      VSL#3 and 22 placebo) completed the study. The main outcome was the change in
      fatty liver severity at 4 months as detected by ultrasonography. Secondary
      outcomes were the changes in triglycerides, insulin resistance as detected by the
      homoeostasis model assessment (HOMA), alanine transaminase (ALT), body mass index
      (BMI), glucagon-like peptide 1 (GLP-1) and activated GLP-1 (aGLP-1). Ordinal and
      linear models with cluster confidence intervals were used to evaluate the
      efficacy of VSL#3 vs. placebo at 4 months. RESULTS: At baseline, moderate and
      severe NAFLD were present in 64% and 36% of PLA children and in 55% and 45% of
      VSL#3 children. The probability that children supplemented with VSL#3 had none,
      light, moderate or severe FL at the end of the study was 21%, 70%, 9% and 0%
      respectively with corresponding values of 0%, 7%, 76% and 17% for the placebo
      group (P < 0.001). No between-group differences were detected in triglycerides,
      HOMA and ALT while BMI decreased and GLP-1 and aGLP1 increased in the VSL#3 group
      (P < 0.001 for all comparisons). CONCLUSIONS: A 4-month supplement of VSL#3
      significantly improves NAFLD in children. The VSL#3-dependent GLP-1 increase
      could be responsible for these beneficial effects. Trial identifier: NCT01650025
      (www.clinicaltrial.gov).

PMID- 24738703
TI  - Imaging the ADHD brain: disorder-specificity, medication effects and clinical
      translation.
AB  - A plethora of magnetic resonance imaging studies have shown that ADHD is
      characterized by multiple functional and structural neural network abnormalities
      beyond the classical fronto-striatal model, including fronto-parieto-temporal,
      fronto-cerebellar and even fronto-limbic networks. There is evidence for a
      maturational delay in brain structure development which likely extends to brain
      function and structural and functional connectivity, but this needs corroboration
      by longitudinal imaging studies. Dysfunction of the ventrolateral prefrontal
      cortex seems to be more pronounced relative to other pediatric disorders and is
      also the most consistent target of acute psychostimulant medication. Future
      studies are likely to focus on using neuroimaging for clinical translation such
      as for individual diagnostic and prognostic classification and as a neurotherapy
      to reverse brain function abnormalities.

PMID- 24738702
TI  - Nitroso-redox balance and mitochondrial homeostasis are regulated by STOX1, a pre
      eclampsia-associated gene.
AB  - AIMS: Storkhead box 1 (STOX1) is a winged-helix transcription factor that is
      implicated in the genetic forms of a high-prevalence human gestational disease,
      pre-eclampsia. STOX1 overexpression confers pre-eclampsia-like transcriptomic
      features to trophoblastic cell lines and pre-eclampsia symptoms to pregnant mice.
      The aim of this work was to evaluate the impact of STOX1 on free radical
      equilibrium and mitochondrial function, both in vitro and in vivo. RESULTS:
      Transcriptome analysis of STOX1-transgenic versus nontransgenic placentas at 16.5
      days of gestation revealed alterations of mitochondria-related pathways.
      Placentas overexpressing STOX1 displayed altered mitochondrial mass and were
      severely biased toward protein nitration, indicating nitroso-redox imbalance in
      vivo. Trophoblast cells overexpressing STOX1 displayed an increased mitochondrial
      activity at 20% O2 and in hypoxia, despite reduction of the mitochondrial mass in
      the former. STOX1 overexpression is, therefore, associated with hyperactive
      mitochondria, resulting in increased free radical production. Moreover, nitric
      oxide (NO) production pathways were activated, resulting in peroxynitrite
      formation. At low oxygen pressure, STOX1 overexpression switched the free radical
      balance from reactive oxygen species (ROS) to reactive nitrogen species (RNS) in
      the placenta as well as in a trophoblast cell line. INNOVATION: In pre-eclamptic
      placentas, NO interacts with ROS and generates peroxynitrite and nitrated
      proteins as end products. This process will deprive the maternal organism of NO,
      a crucial vasodilator molecule. CONCLUSION: Our data posit STOX1 as a genetic
      switch in the ROS/RNS balance and suggest an explanation for elevated blood
      pressure in pre-eclampsia.

PMID- 24738704
TI  - The first Mal de Meleda case in Libya: identification of a SLURP1 mutation.

PMID- 24738705
TI  - Public attitudes about normal and pathological grief.
AB  - Determining public expectations of grief is an important contributor to the
      debate differentiating normal from pathological grief. An international sample of
      348 participants was randomly allocated to 1 of 12 conditions comprising a
      bereavement vignette and self-report items measuring grief expectations and
      social distance. Participants expected grief to decrease steadily between 2 weeks
      and 6 months then stabilize; however, time did not affect social distance. Gender
      of the bereaved and circumstances of death did not influence expectations, but
      did interact to influence social distance. These factors must be accounted for in
      determining a deviation from the norm in diagnostic nosology. 

PMID- 24738706
TI  - Fluorescence enhancement of molecules inside a gold nanomatryoshka.
AB  - Metallic nanoparticles exhibiting plasmonic Fano resonances can provide large
      enhancements of their internal electric near field. Here we show that
      nanomatryoshkas, nanoparticles consisting of an Au core, an interstitial
      nanoscale SiO2 layer, and an Au shell layer, can selectively provide either a
      strong enhancement or a quenching of the spontaneous emission of fluorophores
      dispersed within their internal dielectric layer. This behavior can be understood
      by taking into account the near-field enhancement induced by the Fano resonance
      of the nanomatryoshka, which is responsible for enhanced absorption of the
      fluorophores incorporated into the nanocomplex. The combination of compact size
      and enhanced light emission with internal encapsulation of the fluorophores for
      increased biocompatibility suggests outstanding potential for this type of
      nanoparticle complex in biomedical applications. 

PMID- 24738707
TI  - Excited state photoreaction between the indole side chain of tryptophan and
      halocompounds generates new fluorophores and unique modifications.
AB  - Photoreaction of indole containing compounds with chloroform and other
      trichlorocompounds generates products with redshifted fluorescence. In proteins,
      this reaction can be used for the fluorescent detection of proteins. Little
      characterization of products generated through the photochemical reaction of
      indoles with halocompounds has been done, yet is fundamental for the development
      of other fluorophores, protein labeling agents, and bioactive indole derivatives.
      Here, we have characterized which isomers form in the photoreaction between
      tryptophan and chloroform using (1)H-NMR of tryptophan and methylated derivatives
      to reveal that the two major products that are formed result from modification at
      the 4- and 6-carbon positions of the indole ring. Reaction at position 6
      generates 6-formyl tryptophan and the reaction at position 4 generates an imine
      because the formyl derivative that is initially formed reacts further with the
      tryptophan amine group. The spectroscopic properties and product molecular
      weights of photoproducts formed from photoreaction of tryptophan with other
      trihalo and monohalocompounds are also determined. The indole ring of tryptophan
      can be modified with various additions from halocompounds, including the addition
      of labels to the indole ring via methylene groups. This opens possibilities for
      generating novel tryptophan based fluorophores and protein labeling strategies
      using this photochemistry.

PMID- 24738709
TI  - Kainate receptors in the hippocampus.
AB  - Kainate receptors (KARs) consist of a family of ionotropic glutamate receptors
      composed of the combinations of five subunits, GluK1-GluK5. Although KARs display
      close structural homology with AMPA receptors, they serve quite distinct
      functions. A great deal of our knowledge of the molecular and functional
      properties of KARs comes from their study in the hippocampus. This review aims at
      summarising the functions of KARs in the regulation of the activity of
      hippocampal synaptic circuits at the adult stage and throughout development. We
      focus on the variety of roles played by KARs in physiological conditions of
      activation, at pre- and postsynaptic sites, in different cell types and through
      either metabotropic or ionotropic actions. Finally, we present some of the few
      attempts to link the role of KARs in the regulation of local hippocampal circuits
      to the behavioural functions of the hippocampus in health and diseases. 

PMID- 24738708
TI  - Marine yeast isolation and industrial application.
AB  - Over the last century, terrestrial yeasts have been widely used in various
      industries, such as baking, brewing, wine, bioethanol and pharmaceutical protein
      production. However, only little attention has been given to marine yeasts.
      Recent research showed that marine yeasts have several unique and promising
      features over the terrestrial yeasts, for example higher osmosis tolerance,
      higher special chemical productivity and production of industrial enzymes. These
      indicate that marine yeasts have great potential to be applied in various
      industries. This review gathers the most recent techniques used for marine yeast
      isolation as well as the latest applications of marine yeast in bioethanol,
      pharmaceutical and enzyme production fields. 

PMID- 24738710
TI  - A biomechanical comparison of the vertical jump, power clean, and jump squat.
AB  - The purpose of this study was to compare the kinetics, kinematics, and muscle
      activation patterns of the countermovement jump, the power clean, and the jump
      squat with the expectation of gaining a better understanding of the mechanism of
      transfer from the power clean to the vertical jump. Ground reaction forces,
      electromyography, and joint angle data were collected from 20 trained
      participants while they performed the three movements. Relative to the power
      clean, the kinematics of the jump squat were more similar to those of the
      countermovement jump. The order in which the ankle, knee, and hip began
      extending, as well as the subsequent pattern of extension, was different between
      the power clean and countermovement jump. The electromyography data demonstrated
      significant differences in the relative timing of peak activations in all
      muscles, the maximum activation of the rectus femoris and biceps femoris, and in
      the activation/deactivation patterns of the vastus medialis and rectus femoris.
      The greatest rate of force development during the upward phase of these exercises
      was generated during the power clean (17,254 [Formula: see text]), which was
      significantly greater than both the countermovement jump (3836 [Formula: see
      text]) and jump squat (3517 [Formula: see text]) conditions (P < .001, [Formula:
      see text]).

PMID- 24738711
TI  - Theoretical study on the effect of annelation and carbonylation on the electronic
      and ligand properties of N-heterocyclic silylenes and germylenes: carbene
      comparisons begin to break down.
AB  - Quantum chemical calculations have been carried out to investigate the effect of
      annelation and carbonylation on the electronic and ligand properties of N
      heterocyclic silylenes and germylenes. The thermodynamic stability of these
      ligands has been found to increase with annelation, while the reverse is true for
      carbonylation. This is in sharp contrast to N-heterocyclic carbenes (NHCs) where
      annelation leads to a decrease in their thermodynamic stabilities. Compared to
      nonannelated derivatives, annelated and carbonylated ones are found to be weaker
      sigma donors but better pi acceptors. The effect of carbonylation is more
      pronounced than annelation toward increasing the pi acidity of these ligands.
      Carbonylation at the alpha-position with respect to the N atom attached to the
      Si/Ge center has been found to be the most effective way of enhancing the pi
      acidity of these ligands. The computed natural charges reveal that
      electrophilicity increases upon both annelation and carbonylation. The calculated
      values of (31)P NMR chemical shifts of corresponding phosphinidene adducts of
      these ligands have been found to correlate well with the pi acidity of these
      Si/Ge centers. 

PMID- 24738712
TI  - A best-evidence review of intervention studies for minimizing resistance-to-care
      behaviours for older adults with dementia in nursing homes.
AB  - AIM: To conduct a best-evidence review of non-pharmacological interventions for
      resistance-to-care behaviours of nursing home residents with dementia in a
      personal-care context. BACKGROUND: Resistance to care is a major source of staff
      burnout in nursing homes and it is also a safety issue for the staff. DESIGN:
      Best-evidence review. DATA SOURCES: We searched for non-pharmacological
      intervention studies published from 1990-2012, written in English. REVIEW
      METHODS: The search identified 19 intervention studies that examined the effects
      of interventions to reduce the resistance-to-care behaviours of nursing home
      residents with dementia in a personal-care context. These 19 papers met the
      quality assessment requirements of the critical appraisal criteria for
      experimental studies, which were published by the Joanna Briggs Institute.
      RESULTS: Only three studies were RCTs and the rest were quasi-experimental. The
      sample size ranged from 7-127. Nine music interventions, such as pre-recorded
      music played to a group or playing a resident's preferred music, during his or
      her personal care, resulted in significant reductions in resistance-to-care
      behaviours. Resistance-to-care behaviours also were significantly reduced in
      three of four bathing interventions that focused on person-centred care. In the
      ability-focused interventions, only two out of five studies reported significant
      reductions in resistance-to-care behaviours. CONCLUSION: Non-pharmacological
      interventions are options to consider to reduce resistance-to-care behaviours in
      older people with dementia, even though the evidence level is low, given the lack
      of alternatives. More randomized controlled trials are recommended to confirm the
      effects of non-pharmacological interventions during personal care.

PMID- 24738713
TI  - Continuous positive airway pressure/pressure support pre-oxygenation of morbidly
      obese patients.
AB  - BACKGROUND: Morbidly obese patients are more prone to desaturation of arterial
      blood during apnea with induction of anesthesia than are non-obese. This study
      aimed to assess the effect of low-pressure continuous positive airway pressure
      (CPAP) with pressure support ventilation (PSV) during pre-oxygenation on partial
      oxygen pressure in arterial blood (PaO2 ) immediately after tracheal intubation
      (post-intubation PaO2). METHODS: Forty-four adult patients scheduled for
      laparoscopic gastric bypass surgery were pre-oxygenated with 80% O2 for 2 min,
      randomized either to CPAP 5 cm H2O + PSV 5 cm H2O (CPAP/PSV, n = 22) or neutral
      pressure breathing without CPAP/PSV (control, n = 22). Anesthesia was induced in
      a rapid-sequence protocol and the trachea was intubated without prior mask
      ventilation. Arterial blood gases were measured before pre-oxygenation, before
      induction of anesthesia, and immediately following intubation, before the first
      positive pressure breath. RESULTS: After pre-oxygenation, partial carbondioxide
      pressure was significantly lower in the CPAP/PSV group (4.9 +/- 0.5 kPa), (mean
      +/- standard deviation) than in the control group (5.2 +/- 0.7 kPa) (P = 0.025).
      Post-preoxygenation PaO2 did not differ between the groups, but post-intubation
      PaO2 was significantly higher in the CPAP/PSV group (32.2 +/- 4.1 kPa) than in
      the control group (23.8 +/- 8.8 kPa) (P < 0.001). In the control group, nadir
      oxygen saturation was lower (median 98%, range 83-99%) than in the CPAP/PSV group
      (median 99%, range 97-99%, P = 0.011). CONCLUSIONS: In morbidly obese patients,
      low-pressure CPAP combined with low-pressure PSV during pre-oxygenation resulted
      in better oxygenation, compared with neutral-pressure breathing, and prevented
      desaturation episodes.

PMID- 24738714
TI  - In vitro methods of assessing ocular biocompatibility using THP-1-derived
      macrophages.
AB  - Macrophages play an important role in the elimination of infections, the removal
      of debris and in tissue repair after infection and trauma. In vitro models that
      assess ocular biomaterials for toxicity typically focus on the effects of these
      materials on epithelial or fibroblast cells. This investigation evaluated known
      ocular toxins deposited on model materials for their effects on the viability and
      activation of macrophages. THP-1-derived macrophages were cultured onto silicone
      films (used as a base biomaterial) deposited with chemical toxins (benzalkonium
      chloride (BAK), zinc diethyldithiocarbamate (ZDEC) and lipopolysaccharide (LPS)).
      Utilizing three fluorescent dyes calcein, ethidium homodimer-1 (EthD-1) and
      annexin V, the viability of macrophages attached to the biomaterial was
      determined using confocal microscopy. Propidium iodide (PI) staining and
      alamarBlue(r) (resazurin) reduction were used to assess cell death and metabolic
      activity. CD14, CD16, CD33, CD45, and CD54 expression of adherent macrophages,
      were also evaluated to detect LPS activation of macrophages using flow cytometry.
      The sensitivity of this test battery was demonstrated as significant toxicity
      from treated surfaces with ZDEC (0.001-0.01%), and BAK (0.001%-0.1%) was
      detected. Also, macrophage activation could be detected by measuring CD54
      expression after exposure to adsorbed LPS. These in vitro methods will be helpful
      in determining the toxicity potential of new ocular biomaterials. 

PMID- 24738715
TI  - Enhancing public involvement in assistive technology design research.
AB  - PURPOSE: To appraise the application of accepted good practice guidance on public
      involvement in assistive technology research and to identify its impact on the
      research team, the public, device and trial design. METHODS: Critical reflection
      and within-project evaluation were undertaken in a case study of the development
      of a functional electrical stimulation device. Individual and group interviews
      were undertaken with lay members of a 10 strong study user advisory group and
      also research team members. RESULTS: Public involvement was seen positively by
      research team members, who reported a positive impact on device and study
      designs. The public identified positive impact on confidence, skills, self
      esteem, enjoyment, contribution to improving the care of others and opportunities
      for further involvement in research. A negative impact concerned the challenge of
      engaging the public in dissemination after the study end. CONCLUSIONS: The public
      were able to impact significantly on the design of an assistive technology device
      which was made more fit for purpose. Research team attitudes to public
      involvement were more positive after having witnessed its potential first hand.
      Within-project evaluation underpins this case study which presents a much needed
      detailed account of public involvement in assistive technology design research to
      add to the existing weak evidence base. IMPLICATIONS FOR REHABILITATION: The
      evidence base for impact of public involvement in rehabilitation technology
      design is in need of development. Public involvement in co-design of
      rehabilitation devices can lead to technologies that are fit for purpose.
      Rehabilitation researchers need to consider the merits of active public
      involvement in research.

PMID- 24738716
TI  - Involvement of Wnt5a within the cerebrospinal fluid-contacting nucleus in nerve
      injury-induced neuropathic pain.
AB  - Studies have demonstrated that the cerebrospinal fluid-contacting nucleus (CSF
      CN) is involved in neuropathic pain, but the underlying molecular mechanisms
      still largely remain obscure. Emerging evidence suggests that spinal Wnt5a plays
      a crucial role in regulation of chronic pain. However, little is known about the
      potential role of the supraspinal Wnt5a in the development of chronic pain. To
      investigate whether Wnt5a exists in the CSF-CN and its role in neuropathic pain,
      double-labeled immunofluorescence staining was used to identify the expression of
      Wnt5a in the CSF-CN and western blot analysis of the CSF-CN was employed to
      verify the alteration of Wnt5a protein in the process of neuropathic pain. In the
      present study, we demonstrated that Wnt5a is distributed in the CSF-CN and the
      Wnt5a protein was up-regulated by nerve injury-induced nociceptive stimuli.
      Furthermore, lateral intracerebroventricular injection of Wnt5a antagonist Box5
      attenuated the chronic constriction injury (CCI)-induced neuropathic pain and
      down-regulated the expression of Wnt5a in the CSF-CN. These data extend our
      understanding of the role of Wnt5a in supraspinal site and demonstrate that the
      CSF-CN participates in nerve injury-induced neuropathic pain via the regulation
      of Wnt5a. 

PMID- 24738717
TI  - Anti-inflammatory effects of an ethanolic extract of guava (Psidium guajava L.)
      leaves in vitro and in vivo.
AB  - Plant extracts have been used as a source of medicines for a wide variety of
      human ailments. Among the numerous traditional medicinal herbs, Psidium guajava
      L. (Myrtaceae), commonly known as guava, has long been used in folk medicines as
      a therapeutic agent for the treatment of numerous diseases in East Asian and
      other countries. The aim of this study was to investigate the anti-inflammatory
      activity of an ethanolic leaf extract of P. guajava (guava) in vitro and in vivo.
      Our results demonstrated that guava leaf extract (GLE) significantly inhibited
      lipopolysaccharide (LPS)-induced production of nitric oxide and prostaglandin E2
      in a dose-dependent manner. GLE suppressed the expression and activity of both
      inducible nitric oxide synthase and cyclooxygenase-2 in part through the
      downregulation of ERK1/2 activation in RAW264.7 macrophages. Furthermore, GLE
      exhibited significant anti-inflammatory activity in 2 different animal models
      Freund's complete adjuvant-induced hyperalgesia in the rat and LPS-induced
      endotoxic shock in mice.

PMID- 24738718
TI  - Physiological characterization and genetic modifiers of aberrant root
      thigmomorphogenesis in mutants of Arabidopsis thaliana MILDEW LOCUS O genes.
AB  - Root architecture and growth patterns are plant features that are still poorly
      understood. When grown under in vitro conditions, seedlings with mutations in
      Arabidopsis thaliana genes MLO4 or MLO11 exhibit aberrant root growth patterns
      upon contact with hard surfaces, exemplified as tight root spirals. We used a set
      of physiological assays and genetic tools to characterize this thigmomorphogenic
      defect in detail. We observed that the mlo4/mlo11-associated root curling
      phenotype is not recapitulated in a set of mutants with altered root growth
      patterns or architecture. We further found that mlo4/mlo11-conditioned root
      curling is not dependent upon light and endogenous flavonoids, but is pH
      sensitive and affected by exogenous calcium levels. Based upon the latter two
      characteristics, mlo4-associated root coiling appears to be mechanistically
      different from the natural strong root curvature of the Arabidopsis ecotype
      Landsberg erecta. Gravistimulation reversibly overrides the aberrant
      thigmomorphogenesis of mlo4 seedlings. Mutants with dominant negative defects in
      alpha-tubulin modulate the extent and directionality of mlo4/mlo11-conditioned
      root coils, whereas mutants defective in polar auxin transport (axr4, aux1) or
      gravitropism (pgm1) completely suppress the mlo4 root curling phenotype. Our data
      implicate a joint contribution of calcium signalling, pH regulation, microtubular
      function, polar auxin transport and gravitropism in root thigmomorphogenesis.

PMID- 24738719
TI  - Dermoscopy of angioma serpiginosum: a case report.

PMID- 24738721
TI  - Retracted Association of STAT4 gene polymorphism with systemic lupus
      erythematosus / lupus nephritis risk.
AB  - OBJECTIVE: The association of STAT4 gene polymorphism with systemic lupus
      erythematosus (SLE) / lupus nephritis (LN) results from the published studies is
      still conflicting. This meta-analysis was performed to evaluate the relationship
      between STAT4 rs7574865, rs16833431, rs11889341, rs8179673, rs10168266,
      rs7582694, rs3821236, rs7601754 gene polymorphism and SLE / LN, and to explore
      whether STAT4 gene polymorphism could become a predictive marker for SLE / LN
      risk. METHODS: Association studies were identified from the databases of PubMed,
      Embase, Cochrane Library and CBM-disc (China Biological Medicine Database) as of
      September 1, 2013, and eligible investigations were synthesized using meta
      analysis method. RESULTS: 24 investigations were identified for the analysis of
      association between STAT4 gene polymorphism and SLE, consisting of 31190 patients
      with SLE and 43940 controls. In STAT4 rs7574865, there was a marked association
      between T allele or TT genotype and SLE susceptibility (T: OR=1.53, 95% CI: 1.30
      1.79, P<0.00001; TT: OR=1.60, 95% CI: 1.34-1.92, P<0.00001), and GG homozygous
      was associated with SLE risk (OR=0.62, 95% CI: 0.51-0.75, P<0.00001).
      Furthermore, rs8179673, rs7582694, or rs3821236 minor allele frequency was
      associated with the risk of SLE, but this association was not found in
      rs16833431, rs11889341, rs10168266, rs7601754, however, the number of included
      studies was small and the results were less robust. In addition, STAT4 rs7574865
      gene polymorphism was not associated with the LN risk. CONCLUSIONS: Our results
      indicate that T allele or TT homozygous is a significant risk genetic molecular
      marker to predict the SLE susceptibility and GG genotype is a valuable marker to
      against the SLE risk, but the association was not found for LN. However, more
      investigations are required to further clarify the association of the T allele or
      TT homozygous with SLE / LN susceptibility.

PMID- 24738722
TI  - The incidence of Barrett's oesophagus and oesophageal adenocarcinoma in the
      United Kingdom and The Netherlands is levelling off.
AB  - BACKGROUND: Barrett's oesophagus (BO) is a risk factor for oesophageal
      adenocarcinoma (OAC). Several studies report increasing incidences of BO with
      substantial variation. AIM: To determine age- and sex-stratified incidence rates
      (IR) of BO and OAC. METHODS: Cohort study using two primary care databases in the
      United Kingdom (UK) and the Netherlands (NL) (2000-2012). BO and OAC cases were
      identified using disease-specific READ codes (UK) and free-text search with
      manual validation (NL). Age- and sex-specific incidence rates (IRs) were
      calculated for both BO and OAC. RESULTS: From the study population of 6,885,420
      subjects in the UK, we identified 12,312 incident BO and 40 (0.3%) subsequent
      incident OAC cases. There were 1383 incident BO, and subsequent 5 (0.4%) incident
      OAC cases among the 1,487,191 subjects in the NL. The IR of BO increased linearly
      with age: 15.6/100,000 PYs (UK) and 23.7/100,000 PYs (NL) for patients aged 40-44
      years, increasing to 85.6/100,000 PYs (UK) and 87.0/100,000 PYs (NL) for 70-74
      years. In both the UK and the NL, IR of BO was 2-4 times higher in males than
      females across all age groups. With respect to calendar time, the IR of BO
      increased by 35% (UK) and 41% (NL) from 2000 to 2003, after which IRs remained
      stable until 2012. CONCLUSIONS: The incidence rates of BO in the UK and the NL
      increased until 2003, but levelled off thereafter. Around 0.3% of patients with
      BO developed OAC at least 1 year after BO diagnosis. These findings may help
      tailor endoscopic surveillance strategies among patients with BO.

PMID- 24738723
TI  - Alzheimer's disease from researcher to caregiver: a personal journey and call to
      action.
AB  - The devastating impact of Alzheimer's disease (AD) spares no one. Given the
      economic and societal consequences, research and development for AD is presently
      witnessing a 'call to action,' yet the unmet needs of patients and caregivers are
      enormous. Moreover, despite the scientific advances and growing interest in
      public-private partnerships (PPPs), there are insufficient funds to support
      current and future PPP initiatives that aim to benefit all stakeholders. This
      article highlights a journey based on my own professional experiences as a
      neuroscientist, drug developer, and family member of a loved one suffering from
      AD. From my perspective, we must share our expertise as scientists and
      caregivers, our clinical trial data, our drug development tools, and our
      discoveries - just as we all share the burdens of this dehumanizing disease.

PMID- 24738724
TI  - Skin dimples.
AB  - Skin dimples are a common occurrence in children. Besides being of cosmetic
      significance, they may give an important clue to an underlying genetic or
      metabolic problem. A simplified location-based algorithmic approach to diagnose
      the underlying cause of skin dimples is presented. Clinical significance of
      medically important dimples, especially sacral dimples, its association with
      occult spinal dysraphism, and a cost-effective diagnostic strategy for its
      imaging is discussed. 

PMID- 24738725
TI  - Creating philanthropic foundations to deal with grief: case studies of bereaved
      parents.
AB  - The current study involves the analysis of six bereaved parents' stories and
      argues that the development of philanthropic foundations helped these parents
      make meaning of their children's deaths and find purpose in the midst of their
      grief. Furthermore, philanthropy, as a way of making meaning and finding purpose,
      is a mutually beneficial process because it helps both the bereaved founders and
      the communities the organizations reach. Connections between these narratives and
      the bereavement literature help us better understand the individual/family grief
      process and meaning making, as well as how internal grief states intersect with
      communities. 

PMID- 24738726
TI  - Tunable and directional plasmonic coupling within semiconductor nanodisk
      assemblies.
AB  - Semiconductor nanocrystals are key materials for achieving localized surface
      plasmon resonance (LSPR) excitation in the extended spectral ranges beyond
      visible light, which are critical wavelengths for chemical sensing, infrared
      detection, and telecommunications. Unlike metal nanoparticles which are already
      widely exploited in plasmonics, little is known about the near-field behavior of
      semiconductor nanocrystals. Near-field interactions are expected to vary greatly
      with nanocrystal carrier density and mobility, in addition to properties such as
      nanocrystal size, shape, and composition. Here we demonstrate near-field coupling
      between anisotropic disk-shaped nanocrystals composed of Cu2-xS, a degenerately
      doped semiconductor whose electronic properties can be modulated by Cu content.
      Assembling colloidal nanocrystals into mono- and multilayer films generates
      dipole-dipole LSPR coupling between neighboring nanodisks. We investigate
      nanodisks of varying crystal phases (Cu1.96S, Cu7.2S4, and CuS) and find that
      nanodisk orientation produces a dramatic change in the magnitude and polarization
      direction of the localized field generated by LSPR excitation. This study
      demonstrates the potential of semiconductor nanocrystals for the realization of
      low-cost, active, and tunable building blocks for infrared plasmonics and for the
      investigation of light-matter interactions at the nanoscale. 

PMID- 24738727
TI  - Surfactant-like properties of an amphiphilic alpha-helical peptide leading to
      lipid nanodisc formation.
AB  - Nanodiscs are self-assembled discoidal nanoparticles composed of amphiphilic
      alpha-helical scaffold proteins or peptides that wrap themselves around the
      circumference of a lipid bilayer in a beltlike manner. In this study, an
      amphiphilic helical peptide that mimics helix 10 of human apoA-I was newly
      synthesized by solid phase peptide synthesis using Fmoc chemistry, and its
      physicochemical properties, including surface tension, self-association, and
      solubilization abilities, were evaluated and related directly to nanodisc
      formation. The synthesized peptide having hydrophobic and hydrophilic faces
      behaves like a general surfactant, affording a critical association concentration
      (CAC) of 2.7 * 10(-5) M and a gammaCAC of 51.2 mN m(-1) in aqueous solution.
      Interestingly, only a peptide solution above its CAC was able to microsolubilize
      L-alpha-dimyristoylphosphatidylcholine (DMPC) vesicles, and lipid nanodiscs with
      an average diameter of 9.5 +/- 2.7 nm were observed by dynamic light scattering
      and negative stain transmission electron microscopy. Moreover, the zeta
      potentials of the lipid nanodiscs were measured for the first time as a function
      of pH, and the values changed from positive (20 mV) to negative (-30 mV). In
      particular, nanodisc solutions at acidic pH 4 (20 mV) or basic pH 9 (-20 mV) were
      found to be stable for more than 6 months as a result of the electrostatic
      repulsion between the particles. 

PMID- 24738730
TI  - Probabilistic ictal EEG sources and temporal lobe epilepsy surgical outcome.
AB  - OBJECTIVE: For patients with medication refractory medial temporal lobe epilepsy
      (MTLE), surgery offers the hope of a cure. However, up to 30% of patients with
      MTLE continue to experience disabling seizures after surgery. The reasons why
      some patients do not achieve seizure freedom are poorly understood. A promising
      theory suggests that epileptogenic networks are broadly distributed in surgically
      refractory MTLE, involving regions beyond the medial temporal lobe. In this
      retrospective study, we aimed to investigate the distribution of epileptogenic
      networks in MTLE using Bayesian distributed EEG source analysis from preoperative
      ictal onset recordings. This analysis has the advantage of generating maps of
      source probability, which can be subjected to voxel-based statistical analyses.
      METHODS: We compared 10 patients who achieved post-surgical seizure freedom with
      10 patients who continued experiencing seizures after surgery. Voxel-based
      Wilcoxon tests were employed with correction for multiple comparisons. RESULTS:
      We observed that ictal EEG source intensities were significantly more likely to
      occur in lateral temporal and posterior medial temporal regions in patients with
      continued seizures post-surgery. CONCLUSIONS: Our findings support the theory of
      broader spatial distribution of epileptogenic networks at seizure onset in
      patients with surgically refractory MTLE.

PMID- 24738731
TI  - Toward deep blue nano hope diamonds: heavily boron-doped diamond nanoparticles.
AB  - The production of boron-doped diamond nanoparticles enables the application of
      this material for a broad range of fields, such as electrochemistry, thermal
      management, and fundamental superconductivity research. Here we present the
      production of highly boron-doped diamond nanoparticles using boron-doped CVD
      diamond films as a starting material. In a multistep milling process followed by
      purification and surface oxidation we obtained diamond nanoparticles of 10-60 nm
      with a boron content of approximately 2.3 * 10(21) cm(-3). Aberration-corrected
      HRTEM reveals the presence of defects within individual diamond grains, as well
      as a very thin nondiamond carbon layer at the particle surface. The boron K-edge
      electron energy-loss near-edge fine structure demonstrates that the B atoms are
      tetrahedrally embedded into the diamond lattice. The boron-doped diamond
      nanoparticles have been used to nucleate growth of a boron-doped diamond film by
      CVD that does not contain an insulating seeding layer. 

PMID- 24738728
TI  - Exploratory genotype-phenotype correlations of facial form and asymmetry in
      unaffected relatives of children with non-syndromic cleft lip and/or palate.
AB  - Family relatives of children with nonsyndromic cleft lip with or without cleft
      palate (NSCL/P) who presumably carry a genetic risk yet do not manifest overt
      oral clefts, often present with distinct facial morphology of unknown genetic
      etiology. This study investigates distinct facial morphology among unaffected
      relatives and examines whether candidate genes previously associated with overt
      NSCL/P and left-right body patterning are correlated with such facial morphology.
      Cases were unaffected relatives of individuals with NSCL/P (n = 188) and controls
      (n = 194) were individuals without family history of NSCL/P. Cases and controls
      were genotyped for 20 SNPs across 13 candidate genes for NSCL/P (PAX7, ABCA4
      ARHGAP29, IRF6, MSX1, PITX2, 8q24, FOXE1, TGFB3 and MAFB) and left-right body
      patterning (LEFTY1, LEFTY2, ISL1 and SNAI1). Facial shape and asymmetry
      phenotypes were obtained via principal component analyses and Procrustes analysis
      of variance from 32 coordinate landmarks, digitized on 3D facial images. Case
      control comparisons of phenotypes obtained were performed via multivariate
      regression adjusting for age and gender. Phenotypes that differed significantly
      (P < 0.05) between cases and controls were regressed on the SNPs one at a time.
      Cases had significantly (P < 0.05) more profile concavity with upper face
      retrusion, upturned noses with obtuse nasolabial angles, more protrusive chins,
      increased lower facial heights, thinner and more retrusive lips and more
      protrusive foreheads. Furthermore, cases showed significantly more directional
      asymmetry compared to controls. Several of these phenotypes were significantly
      associated with genetic variants (P < 0.05). Facial height and width were
      associated with SNAI1. Midface antero-posterior (AP) projection was associated
      with LEFTY1. The AP position of the chin was related to SNAI1, IRF6, MSX1 and
      MAFB. The AP position of the forehead and the width of the mouth were associated
      with ABCA4-ARHGAP29 and MAFB. Lastly, facial asymmetry was related to LEFTY1,
      LEFTY2 and SNAI1. This study demonstrates that, genes underlying lip and palate
      formation and left-right patterning also contribute to facial features
      characteristic of the NSCL/P spectrum.

PMID- 24738729
TI  - Activation of alpha2A-containing nicotinic acetylcholine receptors mediates
      nicotine-induced motor output in embryonic zebrafish.
AB  - It is well established that cholinergic signaling has critical roles during
      central nervous system development. In physiological and behavioral studies,
      activation of nicotinic acetylcholine receptors (nAChRs) has been implicated in
      mediating cholinergic signaling. In developing spinal cord, cholinergic
      transmission is associated with neural circuits responsible for producing
      locomotor behaviors. In this study, we investigated the expression pattern of the
      alpha2A nAChR subunit as previous evidence suggested it could be expressed by
      spinal neurons. In situ hybridization and immunohistochemistry revealed that the
      alpha2A nAChR subunits are expressed in spinal Rohon-Beard (RB) neurons and
      olfactory sensory neurons in young embryos. To examine the functional role of the
      alpha2A nAChR subunit during embryogenesis, we blocked its expression using
      antisense modified oligonucleotides. Blocking the expression of alpha2A nAChR
      subunits had no effect on spontaneous motor activity. However, it did alter the
      embryonic nicotine-induced motor output. This reduction in motor activity was not
      accompanied by defects in neuronal and muscle elements associated with the motor
      output. Moreover, the anatomy and functionality of RB neurons was normal even in
      the absence of the alpha2A nAChR subunit. Thus, we propose that alpha2A
      containing nAChRs are dispensable for normal RB development. However, in the
      context of nicotine-induced motor output, alpha2A-containing nAChRs on RB neurons
      provide the substrate that nicotine acts upon to induce the motor output. These
      findings also indicate that functional neuronal nAChRs are present within spinal
      cord at the time when locomotor output in zebrafish first begins to manifest
      itself. 

PMID- 24738732
TI  - Variations in biochemical and histological characteristics of WSSV infected green
      tiger shrimp Penaeus semisulcatus.
AB  - White Spot Syndrome Virus causes viral disease in crustaceans and generates a
      significant burden in the developing nations. Biochemical and immunological
      assays were performed in WSSV infected Penaeus semisulcatus which were monitored
      in different salinity conditions. Continuous exposure of shrimps to WSSV showed a
      reduced life span, indicating the pathogenicity in Penaeidae species. Hence, this
      study is intended to investigate the protective antioxidant potential of the
      innate immune system consisting biochemical and morphological alterations.
      Penaeus semisulcatus challenged with white spot syndrome virus (5.5 * 10(4) copy
      number; WSSV) reared at different salinity 5, 15, 25 (control) and 35 g/L were
      examined after 0-120 h for immunological parameters such as total hemocyte count
      (THC), phenoloxidase (PO) and respiratory burst (RB) and alkaline and acid
      phosphatase activities. After 72 h, the WSSV injected P. semisulcatus tissues
      were histopathologically sectioned and stained. This study would be helpful to
      understand host-pathogen interaction and envisages the improvement of better
      management practices in shrimp aquaculture system.

PMID- 24738734
TI  - Detecting atheromatous plaques in the aortic arch or supra-aortic arteries for
      more accurate stroke subtype classification.
AB  - INTRODUCTION: To investigate the correlations of atheromatous plaques in the
      aortic arch or supra-aortic arteries with intracranial arterial stenosis and
      carotid plaques in stroke patients, and to determine whether taking these plaques
      into account will reduce the proportion of patients in the undetermined etiology
      group. METHODS: We prospectively enrolled 308 ischemic stroke patients, whose
      clinical characteristics and A-S-C-O classifications were compared with analyses
      of intracranial arteries, carotid arteries, aortic arch, and supra-aortic
      arteries. RESULTS: 125(40.6%) patients had plaques in the aortic arch or supra
      aortic arteries, of which 106 (84.8%) had complex plaques. No correlations were
      observed between these plaques and carotid plaques ( p = 0.283) or intracranial
      arterial stenosis ( p = 0.097). After detecting the mobile thrombi in the aortic
      arch and supra-aortic arteries, the proportion of patients in the
      atherothrombosis group was increased from 33.8% to 55.5% ( p = 0.00), whereas the
      proportion of patients in stroke of undetermined etiology group was decreased
      from 19.2% to 11.0% ( p = 0.00). DISCUSSION: Examining only the carotid and
      intracranial arteries may not provide adequate information about large arteries
      in stroke patients. Therefore, it would be better to include a search for
      relevant plaques in the aortic arch or supra-aortic arteries in modern stroke
      workup, for it may lead to more accurate stroke subtype classification and guide
      secondary prevention.

PMID- 24738733
TI  - DNA-mediated signaling by proteins with 4Fe-4S clusters is necessary for genomic
      integrity.
AB  - Iron-sulfur clusters have increasingly been found to be associated with enzymes
      involved in DNA processing. Here we describe a role for these redox clusters in
      DNA-mediated charge-transport signaling in E. coli between DNA repair proteins
      from distinct pathways. DNA-modified electrochemistry shows that the 4Fe-4S
      cluster of DNA-bound DinG, an ATP-dependent helicase that repairs R-loops, is
      redox-active at cellular potentials and ATP hydrolysis increases DNA-mediated
      redox signaling. Atomic force microscopy experiments demonstrate that DinG and
      Endonuclease III (EndoIII), a base excision repair enzyme, cooperate at long
      range using DNA charge transport to redistribute to regions of DNA damage.
      Genetics experiments, moreover, reveal that this DNA-mediated signaling among
      proteins also occurs within the cell and, remarkably, is required for cellular
      viability under conditions of stress. Silencing the gene encoding EndoIII in a
      strain of E. coli where repair by DinG is essential results in a significant
      growth defect that is rescued by complementation with EndoIII but not with an
      EndoIII mutant that is enzymatically active but unable to carry out DNA charge
      transport. This work thus elucidates a fundamental mechanism to coordinate the
      activities of DNA repair enzymes across the genome. 

PMID- 24738735
TI  - Computational study on the acidic constants of chiral Bronsted acids in dimethyl
      sulfoxide.
AB  - The pK(a) values of a series of chiral Bronsted acids, including N
      triflylphosphoramides, bis(sulfonyl)imides, bis(sulfuryl)imides, dicarboxylic
      acids, sulfonic acids, and N-phosphinyl phosphoramides, were predicted by using
      the SMD/M06-2x/6-311++G(2df,2p)//B3LYP/6-31+G(d) method in DMSO. The results
      revealed that the calculated pKa values ranged from -9.06 to 12.18 for different
      types of acids. The influence of acidic strength on reactivity and
      stereoselectivity was discussed using the calculated acidity data. Given that the
      choice of catalyst with appropriate acidity is the primary condition, several new
      catalyst candidates were designed by calculating corresponding pK(a) values of
      parent acids.

PMID- 24738736
TI  - Stimulation of soluble guanylate cyclase prevents cigarette smoke-induced
      pulmonary hypertension and emphysema.
AB  - RATIONALE: Chronic obstructive pulmonary disease (COPD) is a major cause of death
      worldwide. No therapy stopping progress of the disease is available. OBJECTIVES:
      To investigate the role of the soluble guanylate cyclase (sGC)-cGMP axis in
      development of lung emphysema and pulmonary hypertension (PH) and to test whether
      the sGC-cGMP axis is a treatment target for these conditions. METHODS:
      Investigations were performed in human lung tissue from patients with COPD,
      healthy donors, mice, and guinea pigs. Mice were exposed to cigarette smoke (CS)
      for 6 hours per day, 5 days per week for up to 6 months and treated with BAY 63
      2521. Guinea pigs were exposed to CS from six cigarettes per day for 3 months, 5
      days per week and treated with BAY 41-2272. Both BAY compounds are sGC
      stimulators. Gene and protein expression analysis were performed by quantitative
      real-time polymerase chain reaction and Western blotting. Lung compliance,
      hemodynamics, right ventricular heart mass alterations, and alveolar and vascular
      morphometry were performed, as well as inflammatory cell infiltrate assessment.
      In vitro assays of cell adhesion, proliferation, and apoptosis have been done.
      MEASUREMENTS AND MAIN RESULTS: The functionally essential sGC beta1-subunit was
      down-regulated in patients with COPD and in CS-exposed mice. sGC stimulators
      prevented the development of PH and emphysema in the two different CS-exposed
      animal models. sGC stimulation prevented peroxynitrite-induced apoptosis of
      alveolar and endothelial cells, reduced CS-induced inflammatory cell infiltrate
      in lung parenchyma, and inhibited adhesion of CS-stimulated neutrophils.
      CONCLUSIONS: The sGC-cGMP axis is perturbed by chronic exposure to CS. Treatment
      of COPD animal models with sGC stimulators can prevent CS-induced PH and
      emphysema.

PMID- 24738737
TI  - Poisonings requiring admission to the pediatric intensive care unit: A 5-year
      review.
AB  - BACKGROUND: Poisonings represent a significant number of preventable admissions
      to the pediatric intensive care unit (PICU), but data about poisonings requiring
      PICU-level care are limited. OBJECTIVES: To identify the demographics of patients
      admitted with poisonings and characterize their clinical courses related to their
      poisoning. METHODS: All poisonings over a 5-year period (2008-2012) at an
      academic medical center in New England were retrospectively reviewed using
      electronic medical records in an observational case series. Poisonings were
      identified using key search terms within an admissions database. RESULTS: There
      were 273 admissions for poisonings, which represent 8% of total PICU admissions
      over this time period. The poisonings were unintentional in 148 (54%) cases and
      intentional in 125 (46%). The vast majority of poisonings occurred in patients
      either 3 years or below (N = 121, 44%) or 13 years or above (N = 124, 45%). Most
      (96%) admissions were for less than 48 h and 41% were for less than 24 h. Mean
      PICU length of stay was 1.2 + 0.7 days. A total of 468 substances were ingested
      in 54 different drug classes, with analgesics and antidepressants being the most
      common. Eighty-five (31%) poisonings were polypharmaceutical. The most commonly
      used therapies were naloxone, activated charcoal, and benzodiazepines. Twenty
      seven patients (10%) received mechanical ventilation. There was one fatality, an
      adolescent with a polypharmacy overdose in a suicide attempt. CONCLUSION:
      Pediatric poisonings are a significant percentage of admissions to the PICU. The
      majority of poisonings are non-fatal, require supportive care, close monitoring,
      and some specific treatment. Drug classes causing poisonings have changed to a
      higher percentage of opioids in younger patients and atypical antidepressants in
      adolescents.

PMID- 24738738
TI  - Tissue-specific and light-dependent regulation of phytochrome gene expression in
      rice.
AB  - Phytochromes are red- and far red light photoreceptors in higher plants. Rice
      (Oryza sativa L.) has three phytochromes (phyA, phyB and phyC), which play
      distinct as well as cooperative roles in light perception. To gain a better
      understanding of individual phytochrome functions in rice, expression patterns of
      three phytochrome genes were characterized using promoter-GUS fusion constructs.
      The phytochrome genes PHYA and PHYB showed distinct patterns of tissue- and
      developmental stage-specific expression in rice. The PHYA promoter-GUS was
      expressed in all leaf tissues in etiolated seedlings, while its expression was
      restricted to vascular bundles in expanded leaves of light-grown seedlings. These
      observations suggest that light represses the expression of the PHYA gene in all
      cells except vascular bundle cells in rice seedlings. Red light was effective,
      but far red light was ineffective in gene repression, and red light-induced
      repression was not observed in phyB mutants. These results indicate that phyB is
      involved in light-dependent and tissue-specific repression of the PHYA gene in
      rice.

PMID- 24738740
TI  - Application of cooperative iron/copper catalysis to a palladium-free borylation
      of aryl bromides with pinacolborane.
AB  - A new cooperative copper/iron catalysis for the borylation of various aryl
      bromides with pinacolborane, at -10  degrees C, is reported. Use of the toxic,
      precious metal Pd is avoided. The mechanism of the protodebromination side
      reaction is discussed. 

PMID- 24738739
TI  - Potential preventive role of lactic acid bacteria against aflatoxin M1
      immunotoxicity and genotoxicity in mice.
AB  - Aflatoxin M1 (AFM1) is a mycotoxin produced by numerous Aspergillus species in
      pre- or post-harvest cereals and milk. Exposure to AFM1 imparts potent economic
      losses in the livestock industry. Toxicologically, it also causes severe immune
      system problems. The aims of this study were to evaluate a new AFM1
      binding/degrading microorganism for biologic detoxification, to examine its
      ability to degrade AFM1 in liquid medium, and to evaluate its potential for in
      vivo preventative effects against AFM1-induced immunotoxicity and genotoxicity in
      mice. Lactobacillus plantarum MON03 (LP) isolated from Tunisian artisanal butter
      was found to display significant binding ability to AFM1 in PBS (93%) within 24 h
      of incubation. Further, the LP was able to tolerate gastric acidity, bile salts,
      and adhere efficiently to Caco-3 cells in vitro. The in vivo study used Balb/c
      mice that received either vehicle (control), LP only (at 1 * 10(9)CFU/L, ~1 mg/kg
      bw), AFM1 (100 mg/kg bw), or AFM1 + LP daily for 15 days (by gavage); two other
      groups received a single dose of colchicine (4 mg/kg) or mitomycin C (1 mg/kg) as
      positive controls for induction of micronuclei and chromosomal aberrations,
      respectively. The results showed that, compared to in control mice, AFM1
      treatment led to significantly decreased body weight gains, and caused
      cytotoxic/genotoxic effects as indicated by increases in frequencies of
      polychromatic erythrocytes, as well as those with micronucleation (PCEMN) and
      chromosomal aberrations, among bone marrow cells. The concurrent administration
      of LP with AFM1 strongly reduced the adverse effects of AFM1 on each parameter.
      Mice receiving AFM1 + LP co-treatment displayed no significant differences in the
      assayed parameters as compared to the control mice. By itself, the bacteria
      caused no adverse effects. Based on the data, it is concluded that the test
      bacteria could potentially be beneficial in the detoxification of AFM1
      contaminated foods and feeds for humans and animals.

PMID- 24738741
TI  - An overview of nursing in Europe: a SWOT analysis.
AB  - This article sets out a global analysis of the weaknesses, threats, strengths and
      opportunities that define the current situation of nursing in Europe. The nursing
      profession in Europe is suffering from a crisis of self-efficacy with the
      syndrome of burnout being one of its consequences. Other weaknesses include
      shortage of staff, job insecurity, devalued nursing image in society and the lack
      of recognition of emotional and psychological dimensions of care. The threats to
      this profession are linked to the lack of prestige and social recognition and to
      the current economic crisis in Europe. The European economic crisis favours staff
      shortages and increased European migration flow. The strength of the group lies
      in the art of caring, which is its defining feature. Primary Care Nursing and
      Hospital Liaison Nursing demonstrate the great professional adaptability in
      meeting the needs of the ever-changing society. The European Higher Education
      Area and the strengthening of the specialties provide opportunities for the
      nursing profession. Both represent an important progress towards solid
      professionalism that will give nursing greater visibility. Moreover, nursing must
      implement strategies to disseminate its activity and emerge from anonymity.
      Nursing must show society the image it wants to project. 

PMID- 24738742
TI  - Online grief support groups: facilitators' attitudes.
AB  - Although bereaved individuals report positive experiences from participating in
      online support groups, little is known from a facilitator perspective. Using a
      web-based survey, data was collected from a national sample of grief facilitators
      (N = 64). Respondents reported more favorable attitudes toward in-person groups
      over online and indicated a low likelihood of facilitating an online group in the
      next year. However, 62% of the sample (n = 37) reported willingness to refer to
      online groups. This attitude may reflect facilitator acknowledgment of the need
      to increase the presence and availability of grief services; a need that bereaved
      individuals' express, as shown in previous research.

PMID- 24738743
TI  - Disclosure and non-disclosure of concussion and concussion symptoms in athletes:
      review and application of the socio-ecological framework.
AB  - PRIMARY OBJECTIVE: To summarize the factors associated with athletes' disclosure
      and non-disclosure-of sports-related concussion and concussion symptoms within
      the context of the socio-ecological framework and to identify research gaps in
      the current literature. METHODS: Searches using electronic databases identified
      studies written in English, published through October 2013 and addressing some
      aspect of disclosure of concussion and concussion symptoms. The literature search
      aimed to be comprehensive and inclusive of all previous contributions. MAIN
      OUTCOMES AND RESULTS: Of the 30 identified studies, most originated from the US
      (n = 19) and sampled athletes (n = 21) and coaches (n = 10) from high school (n =
      11) and college levels (n = 9). The identified reasons for non-disclosure were
      organized into four levels using the socio-ecological framework: intra-personal
      (e.g. lack of knowledge; internal pressure; sex; concussion history; n = 20
      studies); inter-personal (e.g. others' knowledge/attitudes; external pressure;
      external support; n = 15 studies); environment (e.g. access to concussion
      prevention materials; sports culture; n = 4 studies); and policy (e.g. concussion
      related legislation; n = 3 studies). No study examined all four levels.
      CONCLUSIONS: Research gaps exist concerning factors influencing athletes'
      disclosure of sports-related concussions and concussion symptoms. Notably,
      researchers have focused on intra-personal and inter-personal levels, placing
      less emphasis on the environment and policy levels.

PMID- 24738744
TI  - Comparison of modified Korean cupping method and conventional respiratory suction
      unit for epidermal graft.

PMID- 24738745
TI  - Sasa quelpaertensis leaf extract improves high fat diet-induced lipid
      abnormalities and regulation of lipid metabolism genes in rats.
AB  - Sasa quelpaertensis is a bamboo leaf that is only grown on Jeju Island in South
      Korea. It is used as a bamboo tea that is consumed for therapeutic purposes,
      particularly for its anti-diabetic, diuretic, and anti-inflammatory effects. This
      study investigated the effect of S. quelpaertensis leaf extract (SQE) on high fat
      induced lipid abnormalities and regulation of lipid metabolism-related gene
      expressions in rats. SQE supplementation significantly decreased the levels of
      plasma triglycerides, total cholesterol, and low-density lipoprotein cholesterol
      as well as the atherogenic index. SQE restored levels of plasma high-density
      lipoprotein cholesterol, which were lowered by a high fat diet. Plasma and
      cardiac resistin levels were also significantly decreased by SQE supplementation.
      In adipose tissue, mRNA levels of CAAT/enhancer-binding protein beta (C/EBPbeta)
      were suppressed in the SQE group. SQE supplementation decreased the accumulation
      of lipid droplets, inflammatory cell infiltrations, levels of triglycerides, and
      total lipids in the liver and effectively down-regulated expression of sterol
      regulatory element binding protein-1 (SREBP-1), fatty acid synthetase (FAS), and
      uncoupling protein 2 (UCP-2). These results suggest that SQE may be a potential
      treatment for high fat-related disorders by improving lipid profiles and
      modulating lipid metabolism.

PMID- 24738746
TI  - Addressing the lack of studies in attention-deficit/hyperactivity disorder in
      adults.
AB  - Attention-deficit/hyperactivity disorder (ADHD) is commonly known to occur during
      childhood, characterized by excessive inattention and/or hyperactivity and
      impulsivity as well as lack of emotional self-control and motivation. The
      prevalence of adult ADHD in the general population is estimated to be between 2
      5%. The aim of this review is to provide an overview regarding current
      controversies related to ADHD within the adult population. The concept of ADHD in
      adults has been questioned and criticized by professionals over the last years.
      Overall, adult ADHD is well evidenced based on epidemiological data, genetic
      data, neuroimaging, psychosocial impairment and treatment effectiveness.
      Although, research within this field has been significantly improved, suggestions
      for future research are provided, in order to be able to clarify the remaining
      questions regarding this disorder throughout adulthood. One of the most important
      changes to be made in the near future should be to increase educational training
      on ADHD in adults.

PMID- 24738747
TI  - Savinase, the most suitable enzyme for releasing peptides from lentil (Lens
      culinaris var. Castellana) protein concentrates with multifunctional properties.
AB  - The aim of this study was to produce multifunctional hydrolysates from lentil
      protein concentrates. Four different proteases (Alcalase, Savinase, Protamex, and
      Corolase 7089) and different hydrolysis times were evaluated for their degree and
      pattern of proteolysis and their angiotensin I-converting enzyme (ACE) inhibitory
      and antioxidant activities. Alcalase and Savinase showed the highest proteolytic
      effectiveness (P <= 0.05), which resulted in higher yield of peptides. The
      hydrolysate produced by Savinase after 2 h of hydrolysis (S2) displayed the
      highest ACE-inhibitory (IC50 = 0.18 mg/mL) and antioxidant activity (1.22 MUmol
      of Trolox equiv/mg of protein). Subsequent reverse-phase HPLC-tandem mass
      spectrometric analysis of 3 kDa permeates of S2 showed 32 peptides, mainly
      derived from convicilin, vicilin, and legumin containing bioactive amino acid
      sequences, which makes them potential contributors to ACE-inhibitory and
      antioxidant activities detected. The ACE-inhibitory and antioxidant activities of
      S2 were significantly improved after in vitro gastrointestinal digestion (P <=
      0.05). Multifunctional hydrolysates could encourage value-added utilization of
      lentil proteins for the formulation of functional foods and nutraceuticals. 

PMID- 24738748
TI  - Associated factors to erosive tooth wear and its impact on quality of life in
      children with cerebral palsy.
AB  - To evaluate the presence and associated factors of erosive tooth wear (ETW) in
      children with cerebral palsy (CP), as well as its impact on the oral health
      related quality of life (OHRQoL). Parents of 60 CP children, between 6 and 14
      years of age, answered the Brazilian version of the parental-caregivers
      perception questionnaire (P-CPQ). The ETW diagnosis was performed by a single
      calibrated examiner according to the O'Brien's modified index. Associated factors
      such as family income, behavioral factors, and type of CP were also collected.
      OHRQoL was measured through P-CPQ domains and total score, and Poisson regression
      was used to correlate ETW to associated factors and to the scores. ETW was
      present in 48.3% of the children. The multivariate adjusted model showed that the
      presence of ETW was associated with more than 2 days of soft drink intake per
      week (p = 0.003), daily intake of powdered juice (p = 0.002) and reported
      gastroesophageal reflux (p = 0.016). The family income higher than one Brazilian
      minimum wage showed a positive impact on the CP children's OHRQoL (RR = 0.53; p
      <= 0.001). ETW in CP children is associated to frequent consumption of soft
      drinks, powdered juices, and reported gastroesophageal reflux; however, ETW has
      not a negative impact on the OHRQoL. 

PMID- 24738749
TI  - Uptake of cesium and strontium ions by artificially altered phlogopite.
AB  - Potassium (K(+)) phlogopite was transformed to a vermiculite-like mineral through
      a topotactic reaction under acidic conditions (pH 2) followed by hydrothermal
      treatment with Na(+), Mg(2+), Ca(2+), and Al(3+) cations. The resulting Na(+)-,
      Mg(2+)-, Ca(2+)-, and Al(3+)-altered phlogopites (Phl) denoted as Na-Phl, Mg-Phl,
      Ca-Phl, and Al-Phl, respectively. Na-Phl, Mg-Phl, and Ca-Phl all exhibited the
      same high adsorption capacity as natural vermiculite and the absorption of Cs(+)
      and Sr(2+) ions on these materials followed the Langmuir model. High-angle
      annular dark-field scanning transmission electron microscopy showed that Cs(+)
      ions in the Mg-Phl layers were intercalated deep within the crystal structure,
      along specific interlayer regions. These adsorbed anhydrous Cs(+) ions were
      firmly fixed at the centers of hexagonal rings positioned simultaneously in the
      upper and lower tetrahedral silicate sheets, whereas Sr(2+) ions adsorb into the
      interlayer in the hydrous state. Al-Phl formed a hydroxyl-interlayered
      vermiculite and demonstrated significant selectivity for Cs(+) at very low
      concentrations of the isotope. Consequently, the artificially altered phlogopites
      prepared in this study showed controllable and versatile adsorption capabilities
      making them significantly more suitable than natural vermiculite for Cs and Sr
      decontamination. 

PMID- 24738750
TI  - Post-kala-azar dermal leishmaniasis in pregnancy: hitherto unaccounted.

PMID- 24738752
TI  - Uncovering effects of ex vivo protease activity during proteomics and peptidomics
      sample extraction in rat brain tissue by oxygen-18 labeling.
AB  - In biological samples, proteins and peptides are altered by proteolytic activity.
      The actual ex vivo form of the peptidome or proteome analyzed, therefore, does
      not always reflect the natural in vivo state. Sample stabilization and sample
      treatment are thereby decisive for how far these two states diverge. To assess ex
      vivo formation of peptides, we used enzymatic incorporation of oxygen-18 water
      during proteolysis (PALeO approach) to label ex-vivo-formed peptides in rodent
      brain tissue. Rates of ex-vivo-formed peptides were determined in 25 samples that
      were stabilized and treated by six different protocols, whereby samples were
      subjected to different conditions such as temperature, urea concentration, and
      duration of treatment. Samples were measured by nano LC-Orbitrap-MS, and
      incorporation of oxygen-18 was determined by MS/MS database search and analysis
      of the precursor isotope pattern. Extent of ex vivo degradations was affected
      relevantly by the sample treatment protocol applied and stopped almost completely
      by heat stabilization. Determination of the formation state by oxygen-18
      incorporation by MS/MS database search correlated well to more elaborate analysis
      of the MS isotope pattern. Overall, oxygen-18 labeling in combination with
      shotgun data-acquisition and MS/MS database search offers an adjuvant and easily
      applicable tool to monitor sample quality and fidelity in peptide and
      neuropeptide sample preparations. 

PMID- 24738751
TI  - Expression profile of undifferentiated cell transcription factor 1 in normal and
      cancerous human epithelia.
AB  - Undifferentiated cell Transcription Factor 1 (UTF1) is a chromatin-bound protein
      involved in stem cell differentiation. It was initially reported to be restricted
      to stem cells or germinal tissues. However, recent work suggests that UTF1 is
      also expressed in somatic cells and that its expression may increase during
      carcinogenesis. To further clarify the expression profile of UTF1, we evaluated
      UTF1 expression levels immunohistochemically in eight normal human epithelia
      (from breast, prostate, endometrium, bladder, colon, oesophagus, lung and kidney)
      and their corresponding tumours as well as in several epithelial cell lines. We
      showed UTF1 staining in normal and tumour epithelial tissues, but with varying
      intensities according to the tissue location. In vitro analyses also revealed
      that UTF1 is expressed in somatic epithelial cell lines even in the absence of
      Oct4A and Sox2, its two main known regulators. The comparison of UTF1 levels in
      normal and tumoral tissues revealed significant overexpression in endometrial and
      prostatic adenocarcinomas, whereas lower intensity of the staining was observed
      in renal and colic tumours, suggesting a potential tissue-specific function of
      UTF1. Altogether, these results highlight a potential dual role for UTF1, acting
      either as an oncogene or as a tumour suppressor depending on the tissue. These
      findings also question its role as a specific marker for stem cells. 

PMID- 24738753
TI  - Position statement on interdisciplinary team training in geriatrics: an essential
      component of quality health care for older adults.
AB  - Interdisciplinary team training (IDT) is an important component of ensuring
      quality geriatric care delivery, which can be complex and time intensive,
      requiring coordination of many medical, psychosocial, and therapeutic
      interventions and professionals. The Partnership for Health in Aging (PHA), a
      loose coalition of more than 30 organizations representing healthcare
      professionals who care for older adults supported by the American Geriatrics
      Society, identified IDT training in geriatrics as a priority area in addressing
      the geriatrics workforce shortage described in the 2008 Institute of Medicine
      report, Retooling for An Aging America: Building the Health Care Workforce. A PHA
      Workgroup on Interdisciplinary Team Training in Geriatrics was convened to review
      the literature focused on geriatrics IDT training and to develop a position
      statement that would inform and influence groups involved in the development and
      expansion of academic and continuing education programs in IDT training,
      including professional associations, credentialing and licensing bodies,
      accreditation organizations, and university administrators. There are significant
      challenges to expanding the development and implementation of geriatrics IDT
      training for health professionals, and such training will be successful only with
      substantial and sustained advocacy from the above professional groups. 

PMID- 24738755
TI  - Mate finding, Allee effects and selection for sex-biased dispersal.
AB  - Although dispersal requires context-dependent decision-making in three distinct
      stages (emigration, transit, immigration), these decisions are commonly ignored
      in simple models of dispersal. For sexually reproducing organisms, mate
      availability is an important factor in dispersal decisions. Difficulty finding
      mates can lead to an Allee effect where population growth decreases at low
      densities. Surprisingly, theoretical studies on mate finding and on sex-biased
      dispersal produce opposing predictions: in the former, one sex is predicted to
      move less if the other sex evolves to search more, whereas in the latter, mate
      finding difficulties can select for less sex bias in dispersal when mate finding
      occurs after dispersal. Here, we develop a pair of models to examine the joint
      evolution of dispersal and settlement behaviour. Our first model resolves the
      apparent contradiction from the mate search and dispersal literatures. Our second
      model demonstrates that the relationship between mating system and sex-biased
      dispersal is more complex than a simple contrast between resource defence
      monogamy and female defence polygyny. Our results highlight that a key factor is
      the timing of mating relative to dispersal (before, during, or after). We also
      show that although movement has the potential to alleviate a mate-finding Allee
      effect, in some cases, it can actually exacerbate the effect. 

PMID- 24738754
TI  - Longitudinal white matter changes after traumatic axonal injury.
AB  - Diffusion tensor imaging (DTI) has been useful in showing compromise after
      traumatic axonal injury (TAI) at the chronic stage; however, white matter (WM)
      compromise from acute stage of TAI to chronic stage is not yet well understood.
      This study aims to examine changes in WM integrity following TAI by obtaining
      DTI, on average, 1 d post injury and again approximately seven months post
      injury. Sixteen patients with complicated mild to severe brain injuries
      consistent with TAI were recruited in the intensive care unit of a Level I trauma
      center. Thirteen of these patients were studied longitudinally over the course of
      the first seven months post-injury. The first scan occurred, on average, 1 d
      after injury and the second an average of seven months post-injury. Ten healthy
      individuals, similar to the cohort of patients, were recruited as controls. Whole
      brain WM and voxel-based analyses of DTI data were conducted. DTI metrics of
      interest included: fractional anisotropy (FA), mean diffusivity, axial
      diffusivity (AD), and radial diffusivity (RD). tract-based spatial statistics
      were used to examine DTI metrics spatially. Acutely, AD and RD increased and RD
      positively correlated with injury severity. Longitudinal analysis showed
      reduction in FA and AD (p<0.01), but no change in RD. Possible explanations for
      the microstructural changes observed over time are discussed.

PMID- 24738756
TI  - Compartment syndrome, disseminated intravascular coagulation, pneumonia, and
      acute renal failure due to varicella in a previously healthy child.
AB  - Varicella infections are usually considered to be benign. Although very rare,
      infection of an immunocompetent patient by this virus may result in a severe
      illness. We describe a case of varicella infection in a previously healthy,
      immunocompetent 5-y-old boy, complicated with compartment syndrome, disseminated
      intravascular coagulation (DIC), pneumonia, and acute renal failure. He was
      treated successfully with aciclovir and intravenous immunoglobulins for the
      varicella infection, a fasciotomy for compartment syndrome, and fresh frozen
      plasma for DIC.

PMID- 24738757
TI  - Potential anti-inflammatory effects of maraviroc in HIV-positive patients: a
      pilot study of inflammation, endothelial dysfunction, and coagulation markers.
AB  - Persistent immune activation and chronic inflammation significantly contribute to
      non-AIDS morbidity in HIV-infected patients. The HIV inhibitor maraviroc (MVC)
      targets the cellular chemokine CCR5 HIV co-receptor, which is involved in
      important inflammatory pathways. MVC could have significant anti-inflammatory and
      anti-atherosclerotic effects, also reducing immune activation. We designed a
      pilot study to determine which plasma biomarkers of inflammation, endothelial
      dysfunction, and hypercoagulability were modified by MVC in 2 groups of 10
      patients starting MVC-free or MVC-containing regimens. Ten age- and gender
      matched healthy controls were also included. We found higher levels of all
      inflammatory biomarkers in HIV-infected patients compared to healthy controls.
      Both groups showed decreasing levels of interleukin (IL)-17, IL-10, and
      macrophage inflammatory protein (MIP)-1a following the achievement of viral
      suppression. Vascular cell adhesion molecule (VCAM)-1 levels were decreased in
      the MVC group and increased in the MVC-free group. In conclusion, some
      inflammatory biomarkers tend to decrease with the salvage regimen; MVC was not
      associated with a better impact on these measured markers.

PMID- 24738758
TI  - A cell type-specific view on the translation of mRNAs from ROS-responsive genes
      upon paraquat treatment of Arabidopsis thaliana leaves.
AB  - Oxidative stress causes dramatic changes in the expression levels of many genes.
      The formation of a functional protein through successful mRNA translation is
      central to a coordinated cellular response. To what extent the response towards
      reactive oxygen species (ROS) is regulated at the translational level is poorly
      understood. Here we analysed leaf- and tissue-specific translatomes using a set
      of transgenic Arabidopsis thaliana lines expressing a FLAG-tagged ribosomal
      protein to immunopurify polysome-bound mRNAs before and after oxidative stress.
      We determined transcript levels of 171 ROS-responsive genes upon paraquat
      treatment, which causes formation of superoxide radicals, at the whole-organ
      level. Furthermore, the translation of mRNAs was determined for five cell types:
      mesophyll, bundle sheath, phloem companion, epidermal and guard cells. Mesophyll
      and bundle sheath cells showed the strongest response to paraquat treatment.
      Interestingly, several ROS-responsive transcription factors displayed cell type
      specific translation patterns, while others were translated in all cell types. In
      part, cell type-specific translation could be explained by the length of the 5'
      untranslated region (5'-UTR) and the presence of upstream open reading frames
      (uORFs). Our analysis reveals insights into the translational regulation of ROS
      responsive genes, which is important to understanding cell-specific responses and
      functions during oxidative stress. 

PMID- 24738759
TI  - Antibacterial action of Chlorhexidine/thymol containing varnishes in vitro and in
      vivo.
AB  - OBJECTIVES: The antibacterial activity of two different formulations of a
      chlorhexidine/thymol varnish should be elucidated in vitro and in vivo. METHODS:
      The agar diffusion assay with Cervitec((r)) and CervitecPlus((r)) and three
      reference strains each of streptococci, lactobacilli, actinomyces and periodontal
      pathogens was performed. In a split-mouth study, 40 volunteers applied the test
      (CervitecPlus((r)), solvent water and ethanol) and control (Cervitec((r)),
      solvent ethyl acetate) varnish at buccal recessions of premolar teeth at baseline
      as well as after two, four and seven days. Supra- and subgingival plaques were
      collected 2 weeks before baseline and at the screening appointments.
      Supragingival plaque was analysed for mutans streptococci and lactobacilli and
      subgingival samples for Aggregatibacter actinomycetemcomitans, Fusobacterium
      nucleatum, Porphyromonas gingivalis and Porphyromonas intermedia.
      Friedman/Wilcoxon tests and U-test were used for statistical analysis (P < 0.05).
      RESULTS: Most reference strains were susceptible with inhibition zones (mm) as
      follows: Cervitec((r))/CervitecPlus((r)) streptococci 27 +/- 1.7/21.3 +/- 2.5,
      lactobacilli 26 +/- 9.2/23.7 +/- 4.9, actinomyces 36.3 +/- 6.6/27.3 +/- 1.5,
      periodontal pathogens 18.7 +/- 7.6/18 +/- 1.7. Both varnishes reduced
      significantly the counts of mutans streptococci and lactobacilli in the patients.
      However, no significant differences were found between test and control sides at
      any time. The total counts of periodontal pathogens were low. A tendency to
      higher counts of A. actinomycetemcomitans at the control side could be shown; the
      test side did not harbour significantly higher counts. CONCLUSION: Both varnishes
      may influence the plaque formation and reduce mutans streptococci in
      supragingival plaque.

PMID- 24738760
TI  - Mitochondrial transfer of induced pluripotent stem cell-derived mesenchymal stem
      cells to airway epithelial cells attenuates cigarette smoke-induced damage.
AB  - Transplantation of mesenchymal stem cells (MSCs) holds great promise in the
      repair of cigarette smoke (CS)-induced lung damage in chronic obstructive
      pulmonary disease (COPD). Because CS leads to mitochondrial dysfunction, we aimed
      to investigate the potential benefit of mitochondrial transfer from human-induced
      pluripotent stem cell-derived MSCs (iPSC-MSCs) to CS-exposed airway epithelial
      cells in vitro and in vivo. Rats were exposed to 4% CS for 1 hour daily for 56
      days. At Days 29 and, human iPSC-MSCs or adult bone marrow-derived MSCs (BM-MSCs)
      were administered intravenously to CS-exposed rats. CS-exposed rats exhibited
      severe alveolar destruction with a higher mean linear intercept (Lm) than sham
      air-exposed rats (P < 0.001) that was attenuated in the presence of iPSC-MSCs or
      BM-MSCs (P < 0.01). The attenuation of Lm value and the severity of fibrosis was
      greater in the iPSC-MSC-treated group than in the BM-MSC-treated group (P <
      0.05). This might have contributed to the novel observation of mitochondrial
      transfer from MSCs to rat airway epithelial cells in lung sections exposed to CS.
      In vitro studies further revealed that transfer of mitochondria from iPSC-MSCs to
      bronchial epithelial cells (BEAS-2B) was more effective than from BM-MSCs, with
      preservation of adenosine triphosphate contents. This distinct mitochondrial
      transfer occurred via the formation of tunneling nanotubes. Inhibition of
      tunneling nanotube formation blocked mitochondrial transfer. Our findings
      indicate a higher mitochondrial transfer capacity of iPSC-MSCs than BM-MSCs to
      rescue CS-induced mitochondrial damage. iPSC-MSCs may thus hold promise for the
      development of cell therapy in COPD. 

PMID- 24738761
TI  - Cultural variances in composition of biological and supernatural concepts of
      death: a content analysis of children's literature.
AB  - Children's reasoning about the afterlife emerges naturally as a developmental
      regularity. Although a biological understanding of death increases in accordance
      with cognitive development, biological and supernatural explanations of death may
      coexist in a complementary manner, being deeply imbedded in cultural contexts.
      This study conducted a content analysis of 40 children's death-themed picture
      books in Western Europe and East Asia. It can be inferred that causality and non
      functionality are highly integrated with the naturalistic and supernatural
      understanding of death in Western Europe, whereas the literature in East Asia
      seems to rely on naturalistic aspects of death and focuses on causal
      explanations.

PMID- 24738762
TI  - Solventless mechanosynthesis of N-protected amino esters.
AB  - Mechanochemical derivatizations of N- or C-protected amino acids were performed
      in a ball mill under solvent-free conditions. A vibrational ball mill was used
      for the preparation of N-protected alpha- and beta-amino esters starting from the
      corresponding N-unmasked precursors via a carbamoylation reaction in the presence
      of di-tert-butyl dicarbonate (Boc2O), benzyl chloroformate (Z-Cl) or 9
      fluorenylmethoxycarbonyl chloroformate (Fmoc-Cl). A planetary ball mill proved to
      be more suitable for the synthesis of amino esters from N-protected amino acids
      via a one-pot activation/esterification reaction in the presence of various
      dialkyl dicarbonates or chloroformates. The spot-to-spot reactions were
      straightforward, leading to the final products in reduced reaction times with
      improved yields and simplified work-up procedures. 

PMID- 24738763
TI  - Addressing the problem of ADHD medication as neuroenhancements.
AB  - The prevalence of attention deficit hyperactivity disorder (ADHD) diagnoses is
      rising. ADHD is closely linked to its treatment with medications such as
      methylphenidate and amphetamines, which have popular appeal as neuroenhancement
      drugs by persons without a neurological disorder. The three main reasons for the
      increase in ADHD medication demand, production, and consumption are a) the
      inclusion of milder ADHD diagnoses; b) the vast marketing of ADHD medications by
      the pharmaceutical industry; and c) the illegal diversion of controlled ADHD
      medication to consumers seeking stimulants as neuroenhancements. Rapidly rising
      rates of any neurological disorder - especially a behaviorly-defined disorder
      closely linked to potent medications currently prescribed to more than 5% of the
      population - deserves ongoing scrutiny. Major social and ethical problems arise
      from vague-symptom medicalization, neurological disorder trivialization,
      medication overuse, and controlled substances diversion to healthy persons for
      nonmedical purposes. We argue against the 'spectrumization' of ADHD in an effort
      to curtail further diagnosis creep.

PMID- 24738764
TI  - Assessment of quality of life in patients with psoriasis: a study from Serbia.
AB  - BACKGROUND: Psoriasis has a substantial impact on patients' quality of life.
      OBJECTIVES: The aims of this study were to assess the impact of the clinical
      severity of psoriasis on patients' quality of life and to determine the effects
      of psoriasis-related stress on patients' everyday life. METHODS: The cross
      sectional study was conducted at the Institute of Dermatovenereology, Clinical
      Center of Serbia, Belgrade. The study included 201 patients (124 men and 77
      women), aged 18-70 with a diagnosis of psoriasis, hospitalized or treated as
      outpatients during 2009. For the assessment of patients' quality of life, the
      psoriasis disability index (PDI) was used. The stress related to psoriasis was
      measured with the psoriasis life stress inventory (PLSI) and disease severity
      with the psoriasis area and severity index (PASI). RESULTS: We found moderate
      correlation between PLSI and all PDI subscales and overall score (correlation
      coefficients ranged from 0.334 to 0.521). The correlation between PASI and PDI
      subscales was weak, while we failed to find any significant correlation between
      PASI and the PLSI. The results of multiple regression analysis indicated that
      stress, more severe disease, and lower educational level are significant
      determining factors of a poorer quality of life in patients with psoriasis.
      CONCLUSION: Our results support the importance of assessing the quality of life
      in psoriasis and effects of stress in patients' adjustment to their condition and
      may have important implications for a psychological stress management approach in
      the clinical management of psoriasis.

PMID- 24738765
TI  - Association of pericardial fat volume with coronary atherosclerotic disease
      assessed by CT angiography.
AB  - OBJECTIVE: To investigate the association of pericardial fat volume (PFV) with
      coronary artery disease (CAD) in patients with intermediate pre-test probability
      of ischaemic heart disease assessed by coronary CT angiography. METHODS: From a
      total of 115 consecutive Iraqi patients who underwent 64-multislice multidetector
      CT angiography examinations, only 74 patients (females, 38% and males, 68%) with
      a mean age of 54 +/- 8 years were found to be eligible for statistical analysis.
      The patients were divided into two groups according to the median value of PFV
      (above and below 100 ml). RESULTS: The median value of PFV in our study was 100
      ml (range, 17-319 ml). A significant association was observed between high PFV
      and significant coronary artery stenosis (p = 0.005), between high PFV and
      significant left circumflex stenosis (p = 0.021) and between high PFV and the
      presence of coronary plaque (p = 0.005). Whereas there was no significant
      correlation between high PFV and coronary calcium score (p = 0.188), between high
      PFV and number of diseased coronary vessels (p > 0.3), and between high PFV and
      body weight and body mass index. CONCLUSION: Increased PFV is strongly associated
      with the presence and severity of CAD. ADVANCES IN KNOWLEDGE: Our study
      highlights the role of pericardial fat as an emerging biomarker in cardiovascular
      risk assessment and supports its association with the magnitude of CAD.

PMID- 24738766
TI  - Spontaneous neural fluctuations predict decisions to attend.
AB  - Ongoing variability in neural signaling is an intrinsic property of the brain.
      Often this variability is considered to be noise and ignored. However, an
      alternative view is that this variability is fundamental to perception and
      cognition and may be particularly important in decision-making. Here, we show
      that a momentary measure of occipital alpha-band power (8-13 Hz) predicts choices
      about where human participants will focus spatial attention on a trial-by-trial
      basis. This finding provides evidence for a mechanistic account of decision
      making by demonstrating that ongoing neural activity biases voluntary decisions
      about where to attend within a given moment. 

PMID- 24738768
TI  - Coarse-to-fine categorization of visual scenes in scene-selective cortex.
AB  - Neurophysiological, behavioral, and computational data indicate that visual
      analysis may start with the parallel extraction of different elementary
      attributes at different spatial frequencies and follows a predominantly coarse-to
      fine (CtF) processing sequence (low spatial frequencies [LSF] are extracted
      first, followed by high spatial frequencies [HSF]). Evidence for CtF processing
      within scene-selective cortical regions is, however, still lacking. In the
      present fMRI study, we tested whether such processing occurs in three scene
      selective cortical regions: the parahippocampal place area (PPA), the
      retrosplenial cortex, and the occipital place area. Fourteen participants were
      subjected to functional scans during which they performed a categorization task
      of indoor versus outdoor scenes using dynamic scene stimuli. Dynamic scenes were
      composed of six filtered images of the same scene, from LSF to HSF or from HSF to
      LSF, allowing us to mimic a CtF or the reverse fine-to-coarse (FtC) sequence.
      Results showed that only the PPA was more activated for CtF than FtC sequences.
      Equivalent activations were observed for both sequences in the retrosplenial
      cortex and occipital place area. This study suggests for the first time that CtF
      sequence processing constitutes the predominant strategy for scene categorization
      in the PPA. 

PMID- 24738767
TI  - The decimal effect: behavioral and neural bases for a novel influence on
      intertemporal choice in healthy individuals and in ADHD.
AB  - We identify a novel contextual variable that alters the evaluation of delayed
      rewards in healthy participants and those diagnosed with attention
      deficit/hyperactivity disorder (ADHD). When intertemporal choices are constructed
      of monetary outcomes with rounded values (e.g., $25.00), discount rates are
      greater than when the rewards have nonzero decimal values (e.g., $25.12). This
      finding is well explained within a dual system framework for temporal discounting
      in which preferences are constructed from separate affective and deliberative
      processes. Specifically, we find that round dollar values produce greater
      positive affect than do nonzero decimal values. This suggests that relative
      involvement of affective processes may underlie our observed difference in
      intertemporal preferences. Furthermore, we demonstrate that intertemporal choices
      with rounded values recruit greater brain responses in the nucleus accumbens to a
      degree that correlates with the size of the behavioral effect across
      participants. Our demonstration that a simple contextual manipulation can alter
      self-control in ADHD has implications for treatment of individuals with disorders
      of impulsivity. Overall, the decimal effect highlights mechanisms by which the
      properties of a reward bias perceived value and consequent preferences. 

PMID- 24738769
TI  - The temporal evolution of coarse location coding of objects: evidence for
      feedback.
AB  - Objects occupy space. How does the brain represent the spatial location of
      objects? Retinotopic early visual cortex has precise location information but can
      only segment simple objects. On the other hand, higher visual areas can resolve
      complex objects but only have coarse location information. Thus coarse location
      of complex objects might be represented by either (a) feedback from higher areas
      to early retinotopic areas or (b) coarse position encoding in higher areas. We
      tested these alternatives by presenting various kinds of first- (edge-defined)
      and second-order (texture) objects. We applied multivariate classifiers to the
      pattern of EEG amplitudes across the scalp at a range of time points to trace the
      temporal dynamics of coarse location representation. For edge-defined objects,
      peak classification performance was high and early and thus attributable to the
      retinotopic layout of early visual cortex. For texture objects, it was low and
      late. Crucially, despite these differences in peak performance and timing,
      training a classifier on one object and testing it on others revealed that the
      topography at peak performance was the same for both first- and second-order
      objects. That is, the same location information, encoded by early visual areas,
      was available for both edge-defined and texture objects at different time points.
      These results indicate that locations of complex objects such as textures,
      although not represented in the bottom-up sweep, are encoded later by neural
      patterns resembling the bottom-up ones. We conclude that feedback mechanisms play
      an important role in coarse location representation of complex objects. 

PMID- 24738770
TI  - Self-enhancement influences medial frontal cortex alpha power to social rejection
      feedback.
AB  - Although previous research has demonstrated that individuals are motivated to
      self-enhance, the neurocognitive mechanisms and temporal dynamics of self
      enhancement are poorly understood. The current research examined whether self
      enhancing motivations affect the perceptual processing of social feedback.
      Participants who varied in self-enhancement motivations received accept and
      reject feedback while EEG was recorded. Following this task, we measured
      perceptions of feedback by asking participants to estimate the number of times
      they were rejected. Source localization and time-frequency analyses revealed that
      alpha power in the medial frontal cortex (MFC) completely mediated the
      relationship between self-enhancement motivations and rejection estimates.
      Specifically, greater self-enhancement motivations predicted decreased MFC alpha
      power to reject compared to accept feedback, which predicted decreased rejection
      estimates. These findings suggest that self-enhancement motivations decrease
      perception of social rejection by influencing how the MFC processes social
      feedback. 

PMID- 24738771
TI  - Motion-defined surface segregation in human visual cortex.
AB  - Surface segregation provides an efficient way to parse the visual scene for
      perceptual analysis. Here, we investigated the segregation of a bivectorial
      motion display into transparent surfaces through a psychophysical task and fMRI.
      We found that perceptual transparency correlated with neural activity in the
      early areas of the visual cortex, suggesting these areas may be involved in the
      segregation of motion-defined surfaces. Two oppositely rotating, uniquely colored
      random dot kinematograms (RDKs) were presented either sequentially or in a
      spatially interleaved manner, displayed at varying alternation frequencies.
      Participants reported the color and rotation direction pairing of the RDKs in the
      psychophysical task. The spatially interleaved display generated the percept of
      motion transparency across the range of frequencies tested, yielding ceiling task
      performance. At high alternation frequencies, performance on the sequential
      display also approached ceiling, indicative of perceived transparency. However,
      transparency broke down in lower alternation frequency sequential displays,
      producing performance close to chance. A corresponding pattern mirroring the
      psychophysical data was also evident in univariate and multivariate analyses of
      the fMRI BOLD activity in visual cortical areas V1, V2, V3, V3AB, hV4, and
      V5/MT+. Using gray RDKs, we found significant presentation by frequency
      interactions in most areas; differences in BOLD signal between presentation types
      were significant only at the lower alternation frequency. Multivariate pattern
      classification was similarly unable to discriminate between presentation types at
      the higher frequency. This study provides evidence that early visual cortex may
      code for motion-defined surface segregation, which in turn may enable perceptual
      transparency. 

PMID- 24738772
TI  - EEG frequency tagging to dissociate the cortical responses to nociceptive and
      nonnociceptive stimuli.
AB  - Whether the cortical processing of nociceptive input relies on the activity of
      nociceptive-specific neurons or whether it relies on the activity of neurons also
      involved in processing nonnociceptive sensory input remains a matter of debate.
      Here, we combined EEG "frequency tagging" of steady-state evoked potentials (SS
      EPs) with an intermodal selective attention paradigm to test whether the cortical
      processing of nociceptive input relies on nociceptive-specific neuronal
      populations that can be selectively modulated by top-down attention. Trains of
      nociceptive and vibrotactile stimuli (Experiment 1) and trains of nociceptive and
      visual stimuli (Experiment 2) were applied concomitantly to the same hand, thus
      eliciting nociceptive, vibrotactile, and visual SS-EPs. In each experiment, a
      target detection task was used to focus attention toward one of the two
      concurrent streams of sensory input. We found that selectively attending to
      nociceptive or vibrotactile somatosensory input indistinctly enhances the
      magnitude of nociceptive and vibrotactile SS-EPs, whereas selectively attending
      to nociceptive or visual input independently enhances the magnitude of the SS-EP
      elicited by the attended sensory input. This differential effect indicates that
      the processing of nociceptive input involves neuronal populations also involved
      in the processing of touch, but distinct from the neuronal populations involved
      in vision. 

PMID- 24738773
TI  - Grasping execution and grasping observation activity of single neurons in the
      macaque anterior intraparietal area.
AB  - Primates use vision to guide their actions in everyday life. Visually guided
      object grasping is known to rely on a network of cortical areas located in the
      parietal and premotor cortex. We recorded in the anterior intraparietal area
      (AIP), an area in the dorsal visual stream that is critical for object grasping
      and densely connected with the premotor cortex, while monkeys were grasping
      objects under visual guidance and during passive fixation of videos of grasping
      actions from the first-person perspective. All AIP neurons in this study
      responded during grasping execution in the light, that is, became more active
      after the hand had started to move toward the object and during grasping in the
      dark. More than half of these AIP neurons responded during the observation of a
      video of the same grasping actions on a display. Furthermore, these AIP neurons
      responded as strongly during passive fixation of movements of a hand on a
      scrambled background and to a lesser extent to a shape appearing within the
      visual field near the object. Therefore, AIP neurons responding during grasping
      execution also respond during passive observation of grasping actions and most of
      them even during passive observation of movements of a simple shape in the visual
      field. 

PMID- 24738774
TI  - Electrophysiological evidence for failures of item individuation in crowded
      visual displays.
AB  - Visual perception is strongly impaired when peripheral targets are surrounded by
      nearby distractors, a phenomenon known as visual crowding. One common behavioral
      signature of visual crowding is an increased tendency for observers to mistakenly
      report the features of nearby distractors instead of the target item. Here, our
      goal was to distinguish between two possible explanations of such substitution
      errors. On the one hand, crowding may have its effects after the deployment of
      attention toward-and individuation of-targets and flankers, such that multiple
      individuated perceptual representations compete to guide the behavioral response.
      On the other hand, crowding may prevent the individuation of closely spaced
      stimuli, thereby reducing the number of apprehended items. We attempted to
      distinguish these alternatives using the N2pc, an ERP that has been shown to
      track the deployment of spatial attention and index the number of individuated
      items within a hemifield. N2pc amplitude increased monotonically with set size in
      uncrowded displays, but this set size effect was abolished in crowded visual
      displays. Moreover, these crowding-induced declines in N2pc amplitude predicted
      individual differences in the rate of substitution errors. Thus, crowding-induced
      confusions between targets and distractors may be a consequence of failures to
      individuate target and distractor stimuli during early stages of visual
      selection.

PMID- 24738775
TI  - SERS detection and removal of mercury(II)/silver(I) using oligonucleotide
      functionalized core/shell magnetic silica sphere@Au nanoparticles.
AB  - Heavy metal ions, such as Hg(2+) and Ag(+), pose severe risks in human health and
      the environment. For sensitive detection and selective removal of Hg(2+) and
      Ag(+) ions, here, we demonstrate a surface-enhanced Raman scattering (SERS)
      active platform by employing the oligonucleotide-functionalized magnetic silica
      sphere (MSS)@Au nanoparticles (NPs). This system exploits mismatched T-Hg-T and C
      Ag-C bridges to capture Hg(2+) and Ag(+) ions, exhibiting excellent responses for
      Hg(2+) ions in the range of 0.1-1000 nM and for Ag(+) in the range of 10-1000 nM.
      The assay is highly selective for the target ions and does not respond to other
      metal ions. Additionally, the Hg(2+) and Ag(+) ions in this system can be
      effectively removed from surrounding solutions by an external magnetic field or
      through spontaneous precipitation. Moreover, more than 80% of the MSS@Au NPs can
      be easily recycled with the help of cysteine. We anticipate that the designed
      strategy could be extended to other analytes that can bind to DNA molecules with
      a high affinity, and can be used in many potential applications such as
      environmental renovation, toxin detection, and groundwater analysis. 

PMID- 24738776
TI  - Separation and characterization of phenolic compounds from U.S. pecans by liquid
      chromatography-tandem mass spectrometry.
AB  - The phenolic acids and proanthocyanidins (PACs) of pecans possess bioactive
      properties, which might be useful in retarding the onset of and ameliorating the
      status of certain chronic disease states. There is a general lack of information
      in the literature regarding such compounds, especially the PACs. Crude phenolic
      extracts pooled from eight commercially significant cultivars were selected based
      on their relatively high antioxidant capacities. The pooled extracts were
      separated via Sephadex LH-20 column chromatography into five ethanolic low
      molecular-weight (LMW) fractions and one acetonic high-molecular-weight (HMW)
      fraction. The preparations were then characterized using RP-HPLC-ESI-MS/MS and
      diol-phase HPLC-ESI-MS/MS in order to determine the key constituents present in
      the LMW and HMW fractions, respectively. As previously observed in pecan nutmeat,
      ellagic acid and (+)-catechin were found to be the major phenolics in the LMW
      fractions. The last eluting LMW fraction did not contain phenolic acids; rather
      it possessed PAC monomers and dimers. The HMW fraction comprised a majority of
      its PACs as dimers; yet, monomers, trimers, tetramers, pentamers, and hexamers
      were also separated and characterized. 

PMID- 24738777
TI  - Developments in the field of bioorthogonal bond forming reactions-past and
      present trends.
AB  - In response to the ever increasing need of chemical biology for new tools, a wide
      variety of new, highly selective reactions have been described. Herein we report
      a summary of recent developments and the historical background on bioorthogonal
      ligation reactions.

PMID- 24738778
TI  - Abscisic acid inhibits root growth in Arabidopsis through ethylene biosynthesis.
AB  - When first discovered in 1963, abscisic acid (ABA) was called abscisin II because
      it promotes abscission. Later, researchers found that ABA accelerates abscission
      via ethylene. In Arabidopsis, previous studies have shown that high
      concentrations of ABA inhibit root growth through ethylene signaling but not
      ethylene production. In the present study in Arabidopsis, we found that ABA
      inhibits root growth by promoting ethylene biosynthesis. The ethylene
      biosynthesis inhibitor L-alpha-(2-aminoethoxyvinyl)-glycine reduces ABA
      inhibition of root growth, and multiple mutants of ACS (1-aminocyclopropane-1
      carboxylate synthase) are more resistant to ABA in terms of root growth than the
      wild-type is. Two ABA-activated calcium-dependent protein kinases, CPK4 and
      CPK11, phosphorylate the C-terminus of ACS6 and increase the stability of ACS6 in
      ethylene biosynthesis. Plants expressing an ACS6 mutant that mimics the
      phosphorylated form of ACS6 produce more ethylene than the wild-type. Our results
      reveal an important mechanism by which ABA promotes ethylene production. This
      mechanism may be highly conserved among higher plants.

PMID- 24738779
TI  - Dual fuels: intra-annual variation in the relative importance of benthic and
      pelagic resources to maintenance, growth and reproduction in a generalist
      salmonid fish.
AB  - Ecological systems are often characterized as stable entities. However, basal
      productivity in most ecosystems varies between seasons, particularly in subarctic
      and polar areas. How this variability affects higher trophic levels or entire
      food webs remains largely unknown, especially in these high-latitude regions. We
      undertook a year-long study of benthic (macroinvertebrate) and pelagic
      (zooplankton) resource availability, along with short (day/days: stomach content)
      , medium (month: liver delta(13)C and delta(15)N isotopes)- and long-term
      (season: muscle delta(13)C and delta(15)N isotopes) assessments of resource use
      by a generalist fish, the European whitefish, in a deep, oligotrophic, subarctic
      lake in northern Europe. Due to the long ice-covered winter period, we expected
      to find general benthic reliance throughout the year, but also a seasonal
      importance of zooplankton to the diet, somatic growth and gonadal development of
      whitefish. Benthic and pelagic resource availability varied between seasons: peak
      littoral benthic macroinvertebrate density occurred in mid-winter, whereas
      maximum zooplankton density was observed in summer. Whitefish stomach content
      revealed a reliance on benthic prey items during winter and pelagic prey in
      summer. A seasonal shift from benthic to pelagic prey was evident in liver
      isotope ratios, but muscle isotope ratios indicated a year-round reliance on
      benthic macroinvertebrates. Whitefish activity levels as well as somatic and
      gonadal growth all peaked during the summer, coinciding with the zooplankton peak
      and the warmest water temperature. Stable isotopes of muscle consistently
      depicted the most important resource, benthic macroinvertebrates, whereas short
      term indicators, that is, diet and stable isotopes of liver, revealed the
      seasonal significance of pelagic zooplankton for somatic growth and gonad
      development. Seasonal variability in resource availability strongly influences
      consumer growth and reproduction and may also be important in other ecosystems
      facing pronounced annual weather fluctuations. 

PMID- 24738780
TI  - (1)H NMR serum metabonomics for understanding metabolic dysregulation in women
      with idiopathic recurrent spontaneous miscarriage during implantation window.
AB  - In an attempt to find out the association of metabolic dysregulation with poor
      endometrial receptivity and pregnancy loss, serum metabonomic profiling of women
      with idiopathic recurrent spontaneous miscarriage (IRSM) is carried out and
      compared with fertile controls. (1)H nuclear magnetic resonance (NMR)-based
      metabonomics was used to obtain serum metabolic profiles of 36 women with IRSM
      and 28 proven fertile women during the window of implantation. The acquired data
      were analyzed using multivariate principal component analysis, partial least
      squares-discriminant analysis, and orthogonal projection to latent structure with
      discriminant analysis. A clear metabolic differentiation was evident between IRSM
      and control samples. The distinguishing metabolites, l-lysine, l-arginine, l
      glutamine, l-histidine, l-threonine, l-phenylalanine, and l-tyrosine are
      significantly up-regulated in IRSM as compared to controls. These altered
      metabolites may be involved in the molecular mechanism of exaggerated
      inflammatory response and vascular dysfunction associated with poor endometrial
      receptivity in women with IRSM. The present work proposes a vital association of
      metabolic dysfunction with the disease pathogenesis. 

PMID- 24738781
TI  - Rayleigh-based concept to tackle strong hydrogen fractionation in dual isotope
      analysis-the example of ethylbenzene degradation by Aromatoleum aromaticum.
AB  - Compound-specific isotope analysis (CSIA) is a state-of-the-art analytical tool
      that can be used to establish and quantify biodegradation of pollutants such as
      BTEX compounds at contaminated field sites. Using isotopes of two elements and
      characteristic Lambda values (Lambda) in dual-isotope-plots can provide insight
      into reaction mechanisms because kinetic isotope effects (KIEs) of both elements
      are reflected. However, the concept's validity in the case of reactions that show
      strong isotope fractionation needs to be examined. The anaerobic ethylbenzene
      degradation pathway of Aromatoleum aromaticum is initiated by the ethylbenzene
      dehydrogenase-catalyzed monohydroxylation of the benzylic carbon atom.
      Measurements of stable isotope ratios revealed highly pronounced hydrogen
      fractionation, which could not be adequately described by the classical Rayleigh
      approach. This study demonstrates the nonlinear behavior of hydrogen isotope
      ratios caused by anaerobic ethylbenzene hydroxylation both mathematically and
      experimentally, develops alternative dual plots to enable the comparison of
      reactions by considering the reacting atoms, and illustrates the importance of
      the stereochemical aspects of substrate and product for the quantification of
      hydrogen fractionation in an enzymatic reaction. With regard to field
      application, proposals for an improved CSIA evaluation procedure with respect to
      pronounced hydrogen enrichment are given. 

PMID- 24738782
TI  - Floral associations of cyclocephaline scarab beetles.
AB  - The scarab beetle tribe Cyclocephalini (Coleoptera: Scarabaeidae: Dynastinae) is
      the second largest tribe of rhinoceros beetles, with nearly 500 described
      species. This diverse group is most closely associated with early diverging
      angiosperm groups (the family Nymphaeaceae, magnoliid clade, and monocots), where
      they feed, mate, and receive the benefit of thermal rewards from the host plant.
      Cyclocephaline floral association data have never been synthesized, and a
      comprehensive review of this ecological interaction was necessary to promote
      research by updating nomenclature, identifying inconsistencies in the data, and
      reporting previously unpublished data. Based on the most specific data, at least
      97 cyclocephaline beetle species have been reported from the flowers of 58 plant
      genera representing 17 families and 15 orders. Thirteen new cyclocephaline floral
      associations are reported herein. Six cyclocephaline and 25 plant synonyms were
      reported in the literature and on beetle voucher specimen labels, and these were
      updated to reflect current nomenclature. The valid names of three unavailable
      plant host names were identified. We review the cyclocephaline floral
      associations with respect to inferred relationships of angiosperm orders. Ten
      genera of cyclocephaline beetles have been recorded from flowers of early
      diverging angiosperm groups. In contrast, only one genus, Cyclocephala, has been
      recorded from dicot flowers. Cyclocephaline visitation of dicot flowers is
      limited to the New World, and it is unknown whether this is evolutionary
      meaningful or the result of sampling bias and incomplete data. The most important
      areas for future research include: (1) elucidating the factors that attract
      cyclocephalines to flowers including floral scent chemistry and thermogenesis,
      (2) determining whether cyclocephaline dicot visitation is truly limited to the
      New World, and (3) inferring evolutionary relationships within the Cyclocephalini
      to rigorously test vicarance hypotheses, host plant shifts, and mutualisms with
      angiosperms.

PMID- 24738783
TI  - Regulatory system for the G1-arrest during neuronal development in Drosophila.
AB  - Neuronal network consists of many types of neuron and glial cells. This diversity
      is guaranteed by the constant cell proliferation of neuronal stem cells following
      stop cell cycle re-entry, which leads to differentiation during development.
      Neuronal differentiation occurs mainly at the specific cell cycle phase, the G1
      phase. Therefore, cell cycle exit at the G1 phase is quite an important issue in
      understanding the process of neuronal cell development. Recent studies have
      revealed that aberrant S phase re-entry from the G1 phase often links cellular
      survival. In this review we discuss the different types of G1 arrest on the
      process of neuronal development in Drosophila. We also describe the issue that
      aberrant S phase entry often causes apoptosis, and the same mechanism might
      contribute to sensory organ defects, such as deafness. 

PMID- 24738784
TI  - Effect of several thermoplastic canal filling techniques on surface temperature
      rise on roots with simulated internal resorption cavities: an infrared
      thermographic analysis.
AB  - AIM: To evaluate the surface temperature rise using an infrared thermal imaging
      camera on roots with and without simulated internal resorption cavities, during
      canal filling with injectable (Obtura II), carrier-based (Soft-Core) gutta-percha
      and continuous wave of condensation (System B) techniques. METHODOLOGY: Root
      canals of 60 mandibular premolar teeth were instrumented to an apical size of 40.
      Circular artificial internal resorption cavities with a diameter of 2.40 mm were
      prepared on the root canal walls of 30 teeth. All teeth were divided into six
      groups of 10 specimen and root filled as follows: group 1 (teeth with internal
      resorption): thermoplasticized injectable gutta-percha (Obtura II), group 2
      (teeth without internal resorption): thermoplasticized injectable gutta-percha
      (Obtura II), group 3 (teeth with internal resorption): carrier-based gutta-percha
      (Soft-Core), group 4 (teeth without internal resorption): carrier-based gutta
      percha (Soft-Core), group 5 (teeth with internal resorption): continuous wave of
      condensation (System B) and group 6 (teeth without internal resorption):
      continuous wave of condensation (System B). The surface temperature changes
      during filling of canals were measured with an infrared thermal imaging camera.
      The thermograms were recorded at 2-s intervals over a period of 40 s to determine
      the maximum temperature rise at the apical, middle and cervical thirds of the
      root surface. The data were statistically analysed with one-way anova and Tukey
      HSD post hoc or Kruskal-Wallis and Bonferroni-adjusted Mann-Whitney U-tests if
      appropriate. RESULTS: The temperature rise on the surface of roots with
      artificial resorptive defects was significantly higher compared with the ones
      without defects in the Obtura II and System B groups (P < 0.001). The System B
      group with internal resorption was associated with the maximum temperature rise
      in the apical (4.3 +/- 2.1) and middle (19.5 +/- 8.9) thirds amongst the groups
      (P < 0.001). CONCLUSION: Use of System B and Obtura II for filling canals with
      internal resorptive cavities resulted in surface temperature rise over the
      critical threshold. However, Soft-Core root filling did not increase the
      temperature over 10  degrees C.

PMID- 24738785
TI  - Exclusive chemoselective reduction of imines in the coexistence of aldehydes
      using AuNPore catalyst.
AB  - Aldimines (R(1)HC?NR(2)) were reduced in the coexistence of aldehydes (R(1)CHO)
      with 100% chemoselectivity by the use of AuNPore giving corresponding amines
      (R(1)H2C-NHR(2)) in high chemical yields. 

PMID- 24738786
TI  - Toothbrush efficacy for plaque removal.
AB  - OBJECTIVES: To determine the effectiveness of a novel sonic toothbrush in
      reducing plaque and in maintenance of gingival health when compared to a standard
      manual brush. METHODS: This study was a block-randomized, examiner-blind, two
      treatment, parallel group, single centre clinical investigation. A total of 84
      subjects were enrolled and randomly assigned to receive either the Panasonic EW
      DL90 or an American Dental Association-endorsed manual toothbrush. Subjects were
      instructed to follow a twice-daily brushing regimen without flossing. Plaque
      levels and gingival health were assessed at baseline and after 1 and 3 weeks of
      treatment using the Turesky Modification of the Quigley-Hein Plaque Index and the
      Papillary Bleeding Score. RESULTS: Subjects assigned to the EW-DL90 group had
      significantly lower plaque levels after 1 and 3 weeks of treatment than those in
      the manual group (P = 0.003 and 0.0035, respectively). Both groups showed a
      reduction in plaque levels at Week 3 relative to baseline. The EW-DL90 group had
      significantly lower gingival inflammation scores after 1 week of treatment (P =
      0.0293), but there was no difference between groups after 3 weeks of treatment.
      CONCLUSION: The EW-DL90 toothbrush safely and effectively removes more plaque
      than a standard manual toothbrush. Improvement in gingival inflammation was
      observed after 1 week of treatment. There was no difference in Papillary Bleeding
      Score between the two groups after 3 weeks of treatment. CLINICAL SIGNIFICANCE:
      The newly developed sonic brush (Panasonic EW-DL90) tested in this study was
      found to be more effective than a manual toothbrush at plaque removal. The
      papillary bleeding scores were significantly lower in the sonic brush group after
      1 week of product use. After 3 weeks of product use, both treatment groups had
      similar papillary bleeding scores almost returning to baseline values.

PMID- 24738787
TI  - Dental caries and fluorosis experience of 8-12-year-old children by early-life
      exposure to fluoride.
AB  - BACKGROUND: It is important to evaluate concurrently the benefit for dental
      caries and the risk for dental fluorosis from early exposure to fluoride among
      children. AIM: To evaluate associations of different levels of exposure to
      fluoride in early childhood with dental caries and dental fluorosis experience in
      school children. METHODS: A Child Dental Health Survey (CDHS) was conducted among
      school children in the Australian state of New South Wales (NSW) in 2007. Trained
      and calibrated examination teams conducted oral epidemiologic examinations to
      assess caries experience as decayed, missing or filled tooth surfaces of the
      primary and permanent dentitions (dmfs/DMFS) and fluorosis using the Thylstrup &
      Fejerskov (TF) index on the maxillary central incisors only. A parental
      questionnaire collected information on residential histories and tap water usage
      to enable calculation of percentage of 3-year lifetime exposure to fluoride in
      water. Use of dietary fluoride supplements was also collected. Dental caries and
      fluorosis experience were compared among groups by levels of exposure to fluoride
      from water and fluoride supplements in bivariate and multivariable analysis,
      controlling for socioeconomic factors. RESULTS: Exposure to different fluoride
      sources varied in the group of 2611 children aged 8-12 years. Lower household
      income was significantly associated in both bivariate and multivariable analyses
      with the greater prevalence and severity of primary tooth caries among 8-10-year
      old children and permanent tooth caries among 8-12 year old. Exposure to fluoride
      in water during the first 3 years of life was associated with both caries and
      fluorosis experience observed at age 8-12 years. Having higher percentage of 3
      year lifetime exposure to fluoride in water was associated with higher prevalence
      of mostly mild fluorosis, but significantly lower prevalence and severity of
      caries in the primary and permanent dentitions. CONCLUSION: There were
      significant associations of dental caries and fluorosis experience with sources
      of early childhood fluoride exposure among children aged 8-12 years in New South
      Wales. Exposure to fluoridated water during the first 3 years of life was
      associated with better oral health of school-age children.

PMID- 24738788
TI  - Heat-generating iron oxide nanocubes: subtle "destructurators" of the tumoral
      microenvironment.
AB  - Several studies propose nanoparticles for tumor treatment, yet little is known
      about the fate of nanoparticles and intimate interactions with the heterogeneous
      and ever-evolving tumor environment. The latter, rich in extracellular matrix, is
      responsible for poor penetration of therapeutics and represents a paramount issue
      in cancer therapy. Hence new strategies start aiming to modulate the neoplastic
      stroma. From this perspective, we assessed the efficacy of 19 nm PEG-coated iron
      oxide nanocubes with optimized magnetic properties to mediate mild tumor magnetic
      hyperthermia treatment. After injection of a low dose of nanocubes (700 MUg of
      iron) into epidermoid carcinoma xenografts in mice, we monitored the effect of
      heating nanocubes on tumor environment. In comparison with the long-term fate
      after intravenous administration, we investigated spatiotemporal patterns of
      nanocube distribution, evaluated the evolution of cubes magnetic properties, and
      examined nanoparticle clearance and degradation processes. While inside tumors
      nanocubes retained their magnetic properties and heating capacity throughout the
      treatment due to a mainly interstitial extracellular location, the particles
      became inefficient heaters after cell internalization and transfer to spleen and
      liver. Our multiscale analysis reveals that collagen-rich tumor extracellular
      matrix confines the majority of nanocubes. However, nanocube-mediated
      hyperthermia has the potential to "destructure" this matrix and improve
      nanoparticle and drug penetration into neoplastic tissue. This study provides
      insight into dynamic interactions between nanoparticles and tumor components
      under physical stimulation and suggests that nanoparticle-mediated hyperthermia
      could be used to locally modify tumor stroma and thus improve drug penetration. 

PMID- 24738789
TI  - An ultra-high performance chromatographic method for the determination of
      artemisinin.
AB  - OBJECTIVE: The goal of this study is to develop an ultra-high performance liquid
      chromatographic method for the quantitative determination of artemisinin at very
      low concentrations using selective ion mass spectroscopic detection. MATERIALS
      AND METHODS: Separation was conducted using a C4 100 mm* 2.1 mm column, and the
      mobile phase consisted of an isocratic two-component system consisting of 60% of
      a 0.1% aqueous solution of formic acid and 40% acetonitrile at a flow rate of 0.4
      ml/min. The drug was detected by means of an electrospray mass spectrometer with
      selective ion monitoring of the [M-H2O+H](+) with m/z of 265.3 in positive ion
      mode. RESULTS: The calibration curves of artemisinin obtained from the UPLC/MS
      system were linear in the three ranges analyzed, with a correlation coefficient
      of no less than 0.9996 for all sets of standards. The peak tailing factor for all
      measurements were <=1.7. The method proved to have good repeatability and
      linearity. DISCUSSION: The described analytical method reached a LOQ of 0.010
      ug/ml with an isocratic system and enables an analysis rate of 20 samples per
      hour. The linearity of the standards was excellent for all sets of standards
      analyzed. CONCLUSION: The method presented in this study provides a rapid and
      suitable means for the determination of artemisinin at very low concentrations.
      This is especially significant when performing dissolution studies where, due to
      the low solubility of artemisinin, a method that can measure the drug at nanogram
      levels is necessary.

PMID- 24738790
TI  - Investigation of the potential for direct compaction of a fine ibuprofen powder
      dry-coated with magnesium stearate.
AB  - Intensive dry powder coating (mechanofusion) with tablet lubricants has
      previously been shown to give substantial powder flow improvement. This study
      explores whether the mechanofusion of magnesium stearate (MgSt), on a fine drug
      powder can substantially improve flow, without preventing the powder from being
      directly compacted into tablets. A fine ibuprofen powder, which is both cohesive
      and possesses a low-melting point, was dry coated via mechanofusion with between
      0.1% and 5% (w/w) MgSt. Traditional low-shear blending was also employed as a
      comparison. No significant difference in particle size or shape was measured
      following mechanofusion. For the low-shear blended powders, only marginal
      improvement in flowability was obtained. However, after mechanofusion,
      substantial improvements in the flow properties were demonstrated. Both XPS and
      ToF-SIMS demonstrated high degrees of a nano-scale coating coverage of MgSt on
      the particle surfaces from optimized mechanofusion. The study showed that robust
      tablets were produced from the selected mechanofused powders, at high-dose
      concentration and tablet tensile strength was further optimized via addition of a
      Polyvinylpyrrolidone (PVP) binder (10% w/w). The tablets with the mechanofused
      powder (with or without PVP) also exhibited significantly lower ejection stress
      than those made of the raw powder, demonstrating good lubrication. Surprisingly,
      the release rate of drug from the tablets made with the mechanofused powder was
      not retarded. This is the first study to demonstrate such a single-step dry
      coating of model drug with MgSt, with promising flow improvement, flow-aid and
      lubrication effects, tabletability and also non-inhibited dissolution rate. 

PMID- 24738791
TI  - Effects of third-order torque on frictional force of self-ligating brackets.
AB  - OBJECTIVE: To investigate the effects of third-order torque on frictional
      properties of self-ligating brackets (SLBs). MATERIALS AND METHODS: Three SLBs
      (two passive and one active) and three archwires (0.016 * 0.022-inch nickel
      titanium, and 0.017 * 0.025-inch and 0.019 * 0.025-inch stainless steel) were
      used. Static friction was measured by drawing archwires though bracket slots with
      four torque levels (0 degrees , 10 degrees , 20 degrees , 30 degrees ), using a
      mechanical testing machine (n  =  10). A conventional stainless-steel bracket was
      used for comparison. RESULTS were subjected to Kruskal-Wallis and Mann-Whitney U
      tests. Contact between the bracket and wire was studied using a scanning electron
      microscope. RESULTS: In most bracket-wire combinations, increasing the torque
      produced a significant increase in static friction. Most SLB-wire combinations at
      all torques produced less friction than that from the conventional bracket.
      Active-type SLB-wire combinations showed higher friction than that from passive
      type SLB-wire combinations in most conditions. When increasing the torque, more
      contact between the wall of a bracket slot and the edge of a wire was observed
      for all bracket types. CONCLUSIONS: Increasing torque when using SLBs causes an
      increase in friction, since contact between the bracket slot wall and the wire
      edge becomes greater; the design of brackets influences static friction.

PMID- 24738792
TI  - Iron deficiency in blood donors: a national cross-sectional study.
AB  - BACKGROUND: Iron deficiency (ID) is an important consequence of blood donation.
      The epidemiology of this problem in the blood donor population was therefore
      studied to enable appropriate targeting of potential solutions to donor ID. STUDY
      DESIGN AND METHODS: A nationally representative, cluster-based cross-sectional
      study of Australian blood donors was performed. Donors were eligible for
      inclusion if they fulfilled criteria for blood donation or were deferred due to
      low or falling hemoglobin. Ferritin was measured and demographic and donation
      data were collected. RESULTS: A total of 3094 blood donors were recruited, of
      which samples were collected from 3049 donors; 1873 had exclusively donated whole
      blood (WB only), 242 had exclusively made apheresis donations, and 530 had not
      donated ("new" donors) in the previous 24 months. The prevalence of ID in new
      female donors was 12.0% compared with 1.3% in males. The prevalence of ID in
      female WB-only donors was 26.4%; it increased with donation frequency and
      decreased with age. The prevalence in male WB-only donors was 6.3% with no
      evident change with age or donation frequency. The prevalence of ID in apheresis
      only donors (females 6.3%; males 2.2%) did not significantly exceed that of new
      donors nor did it change with donation frequency. Importantly, the risk of ID
      could not be satisfactorily predicted in an individual donor by his or her anemia
      status or with predictive modeling incorporating demographic and donation data.
      CONCLUSION: ID is especially prevalent in female, premenopausal, frequent WB
      donors. Strategies to combat ID should be implemented, specifically targeting
      this group.

PMID- 24738793
TI  - Comparative study of the effect of narrowband ultraviolet B phototherapy plus
      methotrexate vs. narrowband ultraviolet B alone and methotrexate alone in the
      treatment of plaque-type psoriasis.
AB  - BACKGROUND: Widespread psoriasis has great effects on life. Effective and rapid
      response in the treatment is needed. So this study was done to compare the
      efficacy of combined narrowband ultraviolet-B (NBUVB) plus methotrexate (MTX)
      versus each one alone in the treatment of psoriasis. METHODS: A total of 120
      patients with widespread plaque-type psoriasis were enrolled, but only 113
      patients completed the study. They were divided into three groups randomly, group
      MN (38) received NBUVB plus MTX, group N (38) received NBUVB alone, and group M
      (37) received MTX only. End point of treatment (clearance) was 90% reduction in
      Psoriasis Area and Severity Index (PASI) Score or up to six months, whichever was
      earlier; follow-up was done for one year. RESULTS: The mean number of weeks
      required for achieving clearance was 6.11 +/- 1.28 weeks in group MN, 11.42 +/-
      2.36 weeks in group N, and 20.87 +/- 4.21 weeks in group M (P < 0.0001). The mean
      number of phototherapy sessions was 17.86 +/- 3.74 sessions in group MN, and
      33.51 +/- 6.9 sessions in group N (P < 0.0001). The mean total cumulative dose of
      NBUVB for achieving clearance was 12.13 +/- 4.02 J/cm(2) in group MN, compared
      with 34.48 +/- 13.13 J/cm(2) in group N (P < 0.0001), while the mean total
      cumulative dose of MTX was 116.04 +/- 20.47 mg in group MN compared with 298.63
      +/- 60.26 mg in group M (P < 0.0001). CONCLUSIONS: Combination of NBUVB plus MTX
      provided rapid improvement with less cumulative doses of both therapies compared
      with each one alone in the treatment of psoriasis.

PMID- 24738794
TI  - What is the ke0 and what does it tell me about propofol?

PMID- 24738795
TI  - Pre-habilitation. I: aggregation of marginal gains.

PMID- 24738796
TI  - Pre-habilitation. II: time for a patient-doctor contract?

PMID- 24738797
TI  - GIFTAHo; an improvement on GIFTASuP? New NICE guidelines on intravenous fluids.

PMID- 24738798
TI  - A defence of the NICE guidelines on intravenous fluids.

PMID- 24738799
TI  - A novel technique to determine an 'apparent ke0 ' value for use with the Marsh
      pharmacokinetic model for propofol.
AB  - Debate continues over the most appropriate blood-brain equilibration rate
      constant (ke0) for use with the Marsh pharmacokinetic model for propofol. We
      aimed to define the optimal ke0 value. Sixty-four patients were sedated with
      incremental increases in effect-site target concentration of propofol while using
      six different ke0 values within the range 0.2-1.2 min(-1). Depth of sedation was
      assessed by measuring visual reaction time. A median 'apparent ke0' value of 0.61
      min(-1) (95% CI 0.37-0.78 min(-1)) led to the greatest probability of achieving a
      stable clinical effect when the effect-site target was fixed at the effect-site
      concentration displayed by the target-controlled infusion system, at the time
      when a desired depth of sedation had been reached. By utilising a clinically
      relevant endpoint to derive this value, inter-individual pharmacokinetic and
      pharmacodynamic variability may be accounted for.

PMID- 24738800
TI  - Induction of general anaesthesia by effect-site target-controlled infusion of
      propofol: influence of pharmacokinetic model and ke0 value.
AB  - We studied the use of a new ke0 value (0.6 min(-1)) for the Marsh pharmacokinetic
      model for propofol. Speed of induction and side-effects produced were compared
      with three other target-controlled infusion systems. Eighty patients of ASA
      physical status 1-2 were studied in four groups in a prospective, randomised
      study. Median (IQR [range]) induction times were shorter with the Marsh model in
      effect-site control mode with a ke0 of either 0.6 min(-1) (81 (61-101 [49-302])s,
      p < 0.01), or 1.2 min(-1) (78 (68-208 [51-325])s, p < 0.05), than with the Marsh
      model in blood concentration control (132 (90-246 [57-435])). The Schnider model
      in effect-site control produced induction times that were longer (298 (282-398
      [58-513])s) than those observed with the Marsh model in blood control (p < 0.05),
      or either effect-site control mode (p < 0.001). There were no differences in the
      magnitude of blood pressure changes or frequency of apnoea between groups.

PMID- 24738801
TI  - Evaluation of a large-scale donation of Lifebox pulse oximeters to non-physician
      anaesthetists in Uganda.
AB  - Pulse oximetry is widely accepted as essential monitoring for safe anaesthesia,
      yet is frequently unavailable in resource-limited settings. The Lifebox pulse
      oximeter, and associated management training programme, was delivered to 79 non
      physician anaesthetists attending the 2011 Uganda Society of Anaesthesia Annual
      Conference. Using a standardised assessment, recipients were tested for their
      knowledge of oximetry use and hypoxia management before, immediately following
      and 3-5 months after the training. Before the course, the median (IQR [range])
      test score for the anaesthetists was 36 (34-39 [26-44]) out of a maximum of 50
      points. Immediately following the course, the test score increased to 41 (38-43
      [25-47]); p < 0.0001 and at the follow-up visit at 3-5 months it was 41 (39-44
      [33-49]); p = 0.001 compared with immediate post-training test scores, and 75/79
      (95%) oximeters were in routine clinical use. This method of introduction
      resulted in a high rate of uptake of oximeters into clinical practice and a
      demonstrable retention of knowledge in a resource-limited setting.

PMID- 24738802
TI  - Concluding results from the first phase of the Zurich Unexpected Difficult Airway
      course based on exercise of technical skills.
AB  - We analysed the results of the first phase of the Zurich Unexpected Difficult
      Airway course. Two hundred and twenty-eight staff members performed a total of
      2712 standardised airway rescue procedures with four airway devices:
      SensaScopeTM, LMA FastrachTM, Laryngeal Tube and needle cricothyrodotomy. Four
      consecutive attempts were performed using each device. We analysed the success
      rate and the time needed for successful completion for each attempt and device.
      The success rates and mean (SD) completion times for all participants were 96.2%
      and 30.2 (15.3) s for the SensaScope, 88.1% and 40.4 (17.2) s for the LMA
      Fastrach, 99.0% and 12.1 (10.6) s for the Laryngeal Tube and 99.0% and 12.3 (6.1)
      s for needle cricothyroidotomy. The learning curves resulting from the four
      consecutive attempts with each device showed a clear pattern of improvement. This
      institutional airway training course represents a promising method to improve the
      capability of practitioners to cope with unexpected difficult airway situations.

PMID- 24738803
TI  - Fetal effects of combined spinal-epidural vs epidural labour analgesia: a
      prospective, randomised double-blind study.
AB  - We have compared fetal heart rate patterns, Apgar scores and umbilical cord gas
      values following initiation of labour analgesia using either combined spinal
      epidural or epidural. One hundred and fifteen healthy women requesting neuraxial
      analgesia in the first stage of labour were randomly assigned to receive either
      combined spinal-epidural (n = 62) or epidural analgesia (n = 53). Fetal heart
      rate traces, recorded for 30 min before and 60 min after neuraxial block, were
      categorised as normal, suspicious or pathological according to national
      guidelines. Sixty-one fetal heart rate tracings were analysed in the combined
      spinal-epidural group and 52 in the epidural group. No significant differences
      were found in fetal heart rate patterns, Apgar scores or umbilical artery and
      vein acid-base status between groups. However, in both combined spinal-epidural
      and epidural groups, there was a significant increase in the incidence of
      abnormal fetal heart rate patterns following neuraxial analgesia (p < 0.0001);
      two before compared with eight after analgesia in the combined spinal-epidural
      group and zero before compared with 11 after in the epidural group. These changes
      comprised increased decelerations (p = 0.0045) (combined spinal-epidural group
      nine before and 14 after analgesia, epidural group four before and 16 after),
      increased late decelerations (p < 0.0001) (combined spinal-epidural group zero
      before and seven after analgesia, epidural group zero before and eight after),
      and a reduction in acceleration rate (p = 0.034) (combined spinal-epidural group
      mean (SD) 12.2 (6.7) h(-1) before and 9.9 (6.1) h(-1) after analgesia, epidural
      group 11.0 (7.3) h(-1) before and 8.4 (5.9) h(-1) after). These fetal heart rate
      changes did not affect neonatal outcome in this healthy population.

PMID- 24738804
TI  - Cardiovascular autonomic function testing under non-standardised and standardised
      conditions in cardiovascular patients with type-2 diabetes mellitus.
AB  - Autonomic function tests require standardised test conditions. We compared
      testing under non-standardised and standardised conditions and investigated the
      agreement between heart and pulse rate variability in 30 subjects with diabetes
      mellitus. Deep breathing, Valsalva manoeuvre and quick standing tests showed non
      standardised reproducibility intraclass correlations (95% CI) of 0.96 (0.82
      0.99), 0.96 (0.81-0.99) and 0.75 (-0.98 to 0.94), respectively. Intraclass
      correlations for sustained handgrip and quick standing were poor. Heart and pulse
      rate variability showed high-frequency band intraclass correlations (95% CI) of
      0.65 (-0.07 to 0.89) and 0.47 (-0.88 to 0.85) for the very low-frequency band,
      respectively, 0.68 (0.00-0.90) and 0.70 (-0.09 to 0.91) for the low-frequency
      band, and 0.86 (0.57-0.95) and 0.82 (0.39-0.95) for the high-frequency band.
      Reproducibility under standardised conditions was comparable. The mean difference
      (95% limits of agreement) between heart and pulse rate variability was 0.99 (0.80
      1.22) for very low frequency, 1.03 (0.88-1.21) for low frequency and 1.35 (0.84
      2.16) for high frequency, with a Spearman's correlation coefficient of 1.00, 0.99
      and 0.98, respectively. We demonstrated a high agreement between heart and pulse
      rate variability and acceptable reproducibility with most autonomic function
      tests, heart and pulse rate variability. 

PMID- 24738805
TI  - Cardiac biomarkers in the prediction of risk in the non-cardiac surgery setting.
AB  - B-Type natriuretic peptides and troponin measurements have potential in
      predicting risk in patients undergoing non-cardiac surgery. Using the American
      Heart Association framework for the evaluation of novel biomarkers, we review the
      current evidence supporting the peri-operative use of these two biomarkers. In
      patients having major non-cardiac surgery who are risk stratified using clinical
      risk scores, the measurement of natriuretic peptides and troponin, both before
      and after surgery, significantly improves risk stratification. However, only pre-
      and postoperative natriuretic peptide measurement and postoperative troponin
      measurement have shown clinical utility. It is now important for trials to be
      conducted to determine whether integrating pre- and postoperative natriuretic
      peptide and postoperative troponin measurement into clinical practice is able to
      improve clinical outcomes in patients undergoing non-cardiac surgery. 

PMID- 24738806
TI  - Oxygen cylinder fire--an update.

PMID- 24738807
TI  - Big Data--of the people, for the people, by the people.

PMID- 24738808
TI  - Anaesthetists and accurate database recording.

PMID- 24738809
TI  - Traffic light bougie: what is the safe zone?

PMID- 24738810
TI  - Bougies--or capnography?

PMID- 24738811
TI  - Preloading bougies.

PMID- 24738812
TI  - Further applications of the traffic light system.

PMID- 24738813
TI  - Scalpel-bougie cricothyroidotomy.

PMID- 24738814
TI  - Reducing postoperative delirium.

PMID- 24738815
TI  - Pooled platelet ratio in damage control resuscitation.

PMID- 24738816
TI  - A reply.

PMID- 24738817
TI  - Prothrombin complex concentrate reversal of warfarin in patients with hip
      fracture.

PMID- 24738818
TI  - Three-dimensional interactive model of lumbar spinal structures.

PMID- 24738819
TI  - Malfunction of B. Braun Perifix (r) Epidural Loss of Resistance Syringe.

PMID- 24738820
TI  - Failure of medical air gas outlet.

PMID- 24738821
TI  - Accidental hypoglycaemia caused by an arterial flush drug error.

PMID- 24738822
TI  - Reducing the cost of anaesthesia.

PMID- 24738823
TI  - Cardiovascular adverse effects of newer antidepressants.
AB  - Newer antidepressants that are more selective in their neurotransmitter effects
      include the selective serotonin reuptake inhibitors (SSRIs), serotonin
      norepinephrine reuptake inhibitors (SNRIs), and others (agomelatine, bupropion,
      mirtazapine, reboxetine, vilazodone, vortioxetine). This article systematically
      reviews data from a variety of sources regarding the potential adverse effects of
      these medications on various cardiovascular parameters. Potential biochemical
      mechanisms by which these antidepressants may adversely affect the cardiovascular
      system are also discussed. Antidepressants that are associated with higher
      cardiovascular risk (SNRIs, reboxetine), lower risk (SSRIs), and without current
      evidence of cardiovascular risk (agomelatine, mirtazapine, vilazodone,
      vortioxetine) are identified. The FDA's recommendations regarding citalopram are
      organized and summarized, and situations with higher risk of cardiovascular
      adverse effects are identified.

PMID- 24738824
TI  - A social constructionist account of grief: loss and the narration of meaning.
AB  - In contrast to dominant Western conceptions of bereavement in largely
      intrapsychic terms, the authors argue that grief or mourning is not primarily an
      interior process, but rather one that is intricately social, as the bereaved
      commonly seek meaning in this unsought transition in not only personal and
      familial, but also broader community and even cultural spheres. The authors
      therefore advocate a social constructionist model of grieving in which the
      narrative processes by which meanings are found, appropriated, or assembled occur
      at least as fully between people as within them. In this view, mourning is a
      situated interpretive and communicative activity charged with establishing the
      meaning of the deceased's life and death, as well as the postdeath status of the
      bereaved within the broader community concerned with the loss. They describe this
      multilevel phenomenon drawing first on psychological research on individual self
      narratives that organize life experience into plot structures that display some
      level of consistency over time, whose viability is then negotiated in the
      intimate interpersonal domain of family and close associates. Second, they
      explore public communication, including eulogies, grief accounts in popular
      literature, and elegies. All of these discourses construct the identity of the
      deceased as he or she was, and as she or he is now in the individual and communal
      continuing bonds with the deceased. Finally, they consider different cultural
      contexts to see how expressions of grief are policed to ensure their coherence
      with the prevailing social and political order. That is, the meanings people find
      through the situated interpretive and communicative activity that is grieving
      must either be congruent with the meanings that undergird the larger context or
      represent an active form of resistance against them. 

PMID- 24738825
TI  - Total daily fluoride intake and the relative contributions of foods, drinks and
      toothpaste by 3- to 4-year-old children in the Gaza Strip - Palestine.
AB  - BACKGROUND: Children in Gaza Strip suffer from a high prevalence of dental
      fluorosis. AIMS: To estimate and compare total daily fluoride (F) intake (TDFI)
      and investigate the relative contributions of different sources of F to TDFI, in
      3- to 4-year-old children in Gaza Strip, exposed to low (<0.7 mg/litre), moderate
      (0.7-1.2 mg/litre) or high (>1.2 mg/litre) F concentrations in tap water. DESIGN:
      A 3-day food diary and samples of tap water, drinks, foods, toothpastes and
      toothbrushing expectorate were collected from 216 children receiving low (n =
      81), moderate (n = 72) or high (n = 63) F concentrations in tap water. F
      concentration of samples was analysed using an F-ion-selective electrode. TDFI
      from all sources was estimated. Data were analysed by anova and Tukey's test.
      RESULTS: The mean (+/-SD) F concentration in low, moderate and high F tap waters
      was 0.21(+/-0.15), 0.91(+/-0.13) and 1.71(+/-0.35) mg/litre, respectively. Mean
      (+/-SD) TDFI was 0.02(+/-0.01), 0.04(+/-0.01) and 0.05(+/-0.03) mg/kg bw/day,
      respectively (P < 0.0001). Foods made the largest contribution (63.9%) to TDFI.
      CONCLUSION: Total daily fluoride (F) intake increased as F concentration in tap
      water increased. Foods were the primary source of F. Programmes for monitoring
      fluoride expose should consider the fluoride concentration of water used for food
      preparation and local dietary behaviours.

PMID- 24738826
TI  - Effects of spatial structure of population size on the population dynamics of
      barnacles across their elevational range.
AB  - Explanations for why population dynamics vary across the range of a species
      reflect two contrasting hypotheses: (i) temporal variability of populations is
      larger in the centre of the range compared to the margins because
      overcompensatory density dependence destabilizes population dynamics and (ii)
      population variability is larger near the margins, where populations are more
      susceptible to environmental fluctuations. In both of these hypotheses, positions
      within the range are assumed to affect population variability. In contrast, the
      fact that population variability is often related to mean population size implies
      that the spatial structure of the population size within the range of a species
      may also be a useful predictor of the spatial variation in temporal variability
      of population size over the range of the species. To explore how population
      temporal variability varies spatially and the underlying processes responsible
      for the spatial variation, we focused on the intertidal barnacle Chthamalus dalli
      and examined differences in its population dynamics along the tidal levels it
      inhabits. Changes in coverage of barnacle populations were monitored for 10.5
      years at 25 plots spanning the elevational range of this species. Data were
      analysed by fitting a population dynamics model to estimate the effects of
      density-dependent and density-independent processes on population growth. We also
      examined the temporal mean-variance relationship of population size with
      parameters estimated from the population dynamics model. We found that the
      relative variability of populations tended to increase from the centre of the
      elevational range towards the margins because of an increase in the magnitude of
      stochastic fluctuations of growth rates. Thus, our results supported hypothesis
      (2). We also found that spatial variations in temporal population variability
      were well characterized by Taylor's power law, the relative population
      variability being inversely related to the mean population size. Results suggest
      that understanding the population dynamics of a species over its range may be
      facilitated by taking the spatial structure of population size into account as
      well as by considering changes in population processes as a function of position
      within the range of the species.

PMID- 24738828
TI  - Magnetically induced anisotropic orientation of graphene oxide locked by in situ
      hydrogelation.
AB  - A general method to prepare polymer gels containing anisotropically oriented
      graphene oxide (GO) or reduced graphene oxide (RGO) was developed, by using the
      magnetically induced orientation of GO. Under a magnetic field, an aqueous
      dispersion of GO was gelated by in situ cross-linking polymerization of an acryl
      monomer and a cross-linker. In the resultant hydrogel, the orientation of GO was
      retained even in the absence of the magnetic field, because the gel network
      trapped GO via noncovalent interactions and efficiently suppressed the structural
      relaxation of GO. The locked structure enabled quantitative investigation on the
      magnetic orientation of GO using 2D small-angle X-ray scattering, which revealed
      that GO nanosheets orient parallel to the magnetic field with an order parameter
      of up to 0.80. Systematic studies with varying gelation conditions indicate that
      the present method can afford a wide range of GO-hybridized anisotropic
      materials, in terms of GO alignment direction, sample shape, and GO
      concentration. Also by virtue of the locked structure, the orientation of GO in
      the hydrogel was well preserved throughout the in situ chemical reduction of GO,
      yielding an RGO-hybridized anisotropic hydrogel, as well as the conversion of the
      hydrogel into organo- and ionogels through the replacement of the internal water
      with solvents. As a preliminary demonstration of the present method for practical
      application, a polymer-composite film containing RGO oriented vertical to the
      film surface was prepared, and its anisotropically enhanced electroconductivity
      along the orientation direction of RGO was confirmed by the flash-photolysis time
      resolved microwave conductivity measurement. 

PMID- 24738827
TI  - Differential gene expression of the intermediate and outer interzone layers of
      developing articular cartilage in murine embryos.
AB  - Nascent embryonic joints, interzones, contain a distinct cohort of progenitor
      cells responsible for the formation of the majority of articular tissues.
      However, to date the interzone has largely been studied using in situ analysis
      for candidate genes in the context of the embryo rather than using an unbiased
      genome-wide expression analysis on isolated interzone cells, leaving significant
      controversy regarding the exact role of the intermediate and outer interzone
      layers in joint formation. Therefore, in this study, using laser capture
      microdissection (three biological replicates), we selectively harvested the
      intermediate and outer interzones of mouse embryos at gestational age 15.5 days,
      just prior to cavitation, when the differences between the layers should be most
      profound. Microarray analysis (Agilent Whole Mouse Genome Oligo Microarrays) was
      performed and the differential gene expression between the intermediate interzone
      cells and outer interzone cells was examined by performing a two-sided paired
      Student's t-test and pathway analysis. One hundred ninety-seven genes were
      differentially expressed (>= 2-fold) between the intermediate interzone and the
      outer interzone with a P-value <= 0.01. Of these, 91 genes showed higher
      expression levels in the intermediate interzone and 106 were expressed higher in
      the outer interzone. Pathway analysis of differentially expressed genes suggests
      an important role for inflammatory processes in the interzone layers, especially
      in the intermediate interzone, and hence in joint and articular cartilage
      development. The high representation of genes relevant to chondrocyte hypertrophy
      and endochondral ossification in the outer interzone suggests that it undergoes
      endochondral ossification.

PMID- 24738829
TI  - Serum adiponectin in gestational diabetes and its relation to pregnancy outcome.
AB  - We investigated adiponectin levels in women with gestational diabetes mellitus
      (GDM) and normal glucose tolerance (NGT) at 24-28 gestational weeks. Fasting
      serum adiponectin, glucose and glycated haemoglobin (HbA1c) were determined in 88
      pregnant women, 44 with GDM and 44 with NGT. Pre-pregnancy and current body mass
      indices (BMI), weight gain and pregnancy outcomes were investigated. Serum
      adiponectin was significantly reduced in GDM compared with the NGT group (p =
      0.000). Adiponectin was negatively correlated with age (r = -0.419, p = 0.000);
      glucose (r = -0.263, p = 0.013); HbA1c (r = -0.274, p = 0.01); BMI (pre-pregnancy
      and current) (r = -0.317, p = 0.003 and r = -0.303, p = 0.004) and positively
      correlated with gestational age at delivery (r = 0.278, p = 0.009). The GDM group
      delivered significantly earlier than the NGT group (p = 0.001). Adverse pregnancy
      outcomes and abdominal delivery were higher in the GDM group (p = 0.000, p =
      0.033, respectively), and adiponectin was significantly reduced in patients with
      adverse outcomes (p = 0.003) and abdominal delivery (p = 0.032). Adiponectin is
      reduced in patients with GDM. Association of adiponectin with adverse pregnancy
      outcomes remains to be elucidated.

PMID- 24738830
TI  - Synthesis of proposed aglycone of mandelalide A.
AB  - A highly convergent synthesis of the proposed mandelalide A aglycone is reported.
      The cornerstones of the synthetic strategy include the following: E-selective
      intramolecular Heck cyclization, Masamune-Roush olefination, Stork-Zhao-Wittig
      olefination, modified Prins cyclization; Sharpless asymmetric dihydroxylation
      followed by Williamson-type etherification, Julia-Kocienski olefination, Brown
      crotylation, and Brown allylation reactions. 

PMID- 24738831
TI  - Identification and expression analysis of a putative fatty acidbinding protein
      gene in the Asian honeybee, Apis cerana cerana.
AB  - Fatty acid-binding proteins (FABPs) play pivotal roles in cellular signaling,
      gene transcription, and lipid metabolism in vertebrates and invertebrates. In
      this study, a putative FABP gene, referred to as AccFABP, was isolated from the
      Asian honeybee, Apis cerana cerana Fabricius (Hymenoptera: Apidae). The full
      length cDNA consisted of 725 bp, and encoded a protein of 204 amino acids.
      Homology and phylogenetic analysis indicated that AccFABP was a member of the
      FABP multifamily. The genomic structure of this gene, which was common among FABP
      multifamily members, spanned 1,900 bp, and included four exons and three introns.
      Gene expression analysis revealed that AccFABP was highly expressed in the dark
      pigmented phase of pupal development, with peak expression observed in the fat
      bodies of the dark-pigmented phase pupae. The AccFABP transcripts in the fat body
      were upregulated by exposure to dietary fatty acids such as conjugated linoleic
      acid, docosahexaenoic acid, and arachidonic acid. Transcription factor binding
      sites for Caudal-Related Homeobox and functional CCAAT/enhancer binding site,
      which were respectively associated with tissue expression and lipid metabolism,
      were detected in the 5' promoter sequence. The evidence provided in the present
      study suggests that AccFABP may regulate insect growth and development, and lipid
      metabolism.

PMID- 24738832
TI  - Sodium-promoted Pd/TiO2 for catalytic oxidation of formaldehyde at ambient
      temperature.
AB  - Catalytic oxidation of formaldehyde (HCHO) to CO2 at ambient conditions is of
      great interest for indoor HCHO purification. Here, we report that sodium-doped
      Pd/TiO2 is a highly effective catalyst for the catalytic oxidation of HCHO at
      room temperature. It was observed that Na doping has a dramatic promotion effect
      on the Pd/TiO2 catalyst and that nearly 100% HCHO conversion could be achieved
      over the 2Na-Pd/TiO2 catalyst at a GHSV of 95000 h(-1) and HCHO inlet
      concentration of 140 ppm at 25  degrees C. The mechanism of the Na-promotion
      effect was investigated by using Brunauer-Emmett-Teller (BET), X-ray diffraction
      (XRD), CO chemisorption, Temperature-programmed reduction by H2 (H2-TPR), X-ray
      photoelectron spectroscopy (XPS) and temperature-programmed desorption of O2 (O2
      TPD) methods. The results showed that Na species addition can induce and further
      stabilize a negatively charged and well-dispersed Pd species, which then
      facilitates the activation of H2O and chemisorbed oxygen, therefore resulting in
      the high performance of the 2Na-Pd/TiO2 catalyst for the ambient HCHO
      destruction. 

PMID- 24738833
TI  - Pomalidomide for the treatment of relapsed-refractory multiple myeloma: a review
      of biological and clinical data.
AB  - Despite the improvements thanks to the introduction of proteasome inhibitors and
      immunomodulatory drugs (IMiDs), nearly all myeloma patients eventually become
      refractory to these drugs. Consequently, the outcome of these patients is very
      poor. Pomalidomide is a new IMiD with a similar structure to the commonly used
      IMiD thalidomide and lenalidomide. Pomalidomide exhibited more potent anti
      myeloma activity and a similar favorable safety profile compared with thalidomide
      and lenalidomide. In Phase I-II studies pomalidomide plus low-dose dexamethasone
      demonstrated activity in myeloma patients refractory to both bortezomib and
      IMiDs. Based on the results of a Phase III trial, the FDA and EMA agencies
      granted accelerated approval to pomalidomide, which is now considered a new
      effective strategy for relapsed and/or refractory myeloma patients. Very
      promising results were obtained when pomalidomide-dexamethasone was used in
      combination with other compounds. This review provides updated information about
      pharmacokinetics, mechanism of action, resistance, clinical efficacy and safety
      of pomalidomide. 

PMID- 24738834
TI  - Chagas disease, a risk factor for high blood pressure.
AB  - BACKGROUND: Chagas disease is a parasite infection caused by the protozoan
      Trypanosoma cruzi. Its most common complications is chronic Chagas heart disease
      but impairments of the systemic vasculature also has been observed. Although the
      different mechanisms that regulate blood pressure are disrupted, to our knowledge
      data on the association of hypertension and chronic Chagas disease are scarce. In
      this regard we evaluate whether Chagas disease constitutes a high blood pressure
      risk factor. MATERIALS AND METHODS: We recruited 200 individuals, half of them
      with positive serology for T. cruzi. They were subjected to a complete clinical
      examination. RESULTS: The mean age of sampled individuals was 46.7 +/- 12.3, and
      the mean of systolic and diastolic blood pressure were 124 +/- 12 mmHg and 82 +/-
      10 mmHg, respectively. There were no between-group differences regarding age, sex
      distribution or body mass index. Chagas disease contributed significantly to high
      blood pressure (OR = 4, 95% CI 1.8323-7.0864, p = 0.0002). CONCLUSION: Our
      results reveal an important association between Chagas disease and high blood
      pressure, which should be contemplated by physicians in order to promote
      preventive cardiovascular actions in patients with Chagas disease.

PMID- 24738835
TI  - Comparison of seven hepatitis B virus (HBV) nucleic acid testing assays in
      selected samples with discrepant HBV marker results from United States blood
      donors.
AB  - BACKGROUND: Sensitive triplex nucleic acid tests (NATs) are implemented for blood
      donation screening worldwide. Assays have variable ability to detect low-level
      hepatitis B virus (HBV) DNA. At borderline DNA detection levels, where Poisson
      distribution impacts results, distinguishing true-positive from false-positive
      results is challenging. Algorithms are needed to confirm such low-level HBV DNA
      positive samples. STUDY DESIGN AND METHODS: A total of 135 blood donor samples
      reactive by one or more HBV markers that provided discrepant results were tested
      undiluted with four commercial NATs: Ultrio, Ultrio Plus, MPX, and a quantitative
      assay (SuperQuant). To further explore discrepancies, three additional in-house
      NATs including real-time polymerase chain reaction (PCR) and nested PCR and
      sequencing were performed. RESULTS: The numbers reactive of these 135 "difficult"
      samples by four commercial NATs were as follows: 39 of 107 (36%) with SuperQuant,
      40 (30%) with Ultrio, 100 (74%) with Ultrio Plus, and 102 (76%) with MPX. Of the
      seven NATs, 109 (81%) samples were reactive by at least two assays and thus
      considered confirmed positive of which 67 (50%) generated a sequence. Ultrio Plus
      and MPX performed similarly as above (80%-85% detected of 109 and 81%-90% of 67,
      respectively). Older (median, 49 years), HBV core antibody-reactive donors
      carried predominantly Genotype A (58%) with high-frequency amino acid
      substitutions in the major hydrophilic region of the S-protein. Younger (median,
      24 years) hepatitis B surface antigen-positive donors carried wild-type strains
      predominantly Genotype B (32%) and E (24%), the latter in an apparent cluster.
      CONCLUSIONS: Highly sensitive NATs require new confirmatory algorithms as
      presented optimally using different genomic regions or sequence generation. The
      introduction of immigration-related HBV genotypes may impact HBV epidemiology in
      the United States.

PMID- 24738836
TI  - Early hemorrhagic progression of traumatic brain contusions: frequency,
      correlation with coagulation disorders, and patient outcome: a prospective study.
AB  - The focus of this paper is to identify and quantify risk factors for early
      hemorrhagic progression of brain contusions (HPC) in patients with traumatic
      brain injury (TBI) and to evaluate their impact on patients' outcome. Further,
      based on abnormal values in routine blood tests, the role of trauma-induced
      coagulopathy is analyzed in detail. Therefore, a prospective study of 153 TBI
      patients was completed at one institution between January 2008 and June 2012. The
      collected data included demographics, initial Glasgow Coma Scale pupillary
      response, initial and 6 h follow-up computed tomography scan findings,
      coagulation parameters (international normalized ratio, partial thromboplastin
      time, platelet count, fibrinogen, D-dimer and factor XIII), as well as outcome
      data using the modified Rankin score at discharge and after one year. The overall
      rate of early HPC within the first 6 h was 43.5%. The frequency of coagulopathy
      was 47.1%. When analyzing for risk factors that independently influenced outcome
      in the form of mRS >=4 at both points, the following variables appeared: elevated
      D-dimer level (>=10,000 MUg/L), HPC, and initial brain contusions >=3 cm.
      Patients sustaining early HPC had a hazard ratio of 5.4 for unfavorable outcome
      at discharge (p=0.002) and of 3.9 after one year (p=0.006). Overall, patients who
      developed early HPC were significantly more likely to be gravely disabled or to
      die. Unfavorable neurological outcome after an isolated TBI is determined largely
      by early HPC and coagulopathy, which seem to occur very frequently in TBI
      patients, irrespective of the severity of the trauma.

PMID- 24738837
TI  - How effective is self-weighing in the setting of a lifestyle intervention to
      reduce gestational weight gain and postpartum weight retention?
AB  - Self-weighing is important for weight management in general populations; however
      its role in optimising gestational weight gain is less clear. Our randomised
      trial in early pregnancy found regular self-weighing when combined with a self
      management intervention, optimised weight gain at 28 weeks gestation (5.66 +/-
      2.6 kg vs 7.03 +/- 3.56 kg, P = 0.02) and reduced postpartum weight retention (
      0.57 +/- 3.94 kg vs 1.48 +/- 5.49 kg, P < 0.05) compared with control
      participants. Results highlight the importance of self-monitoring strategies
      during pregnancy. 

PMID- 24738838
TI  - Nuclear magnetic resonance metabolomics of iron deficiency in soybean leaves.
AB  - Iron (Fe) deficiency is an important agricultural concern that leads to lower
      yields and crop quality. A better understanding of the condition at the
      metabolome level could contribute to the design of strategies to ameliorate Fe
      deficiency problems. Fe-sufficient and Fe-deficient soybean leaf extracts and
      whole leaves were analyzed by liquid (1)H nuclear magnetic resonance (NMR) and
      high-resolution magic-angle spinning NMR spectroscopy, respectively. Overall, 30
      compounds were measurable and identifiable (comprising amino and organic acids,
      fatty acids, carbohydrates, alcohols, polyphenols, and others), along with 22
      additional spin systems (still unassigned). Thus, metabolite differences between
      treatment conditions could be evaluated for different compound families
      simultaneously. Statistically relevant metabolite changes upon Fe deficiency
      included higher levels of alanine, asparagine/aspartate, threonine, valine, GABA,
      acetate, choline, ethanolamine, hypoxanthine, trigonelline, and polyphenols and
      lower levels of citrate, malate, ethanol, methanol, chlorogenate, and 3-methyl-2
      oxovalerate. The data indicate that the main metabolic impacts of Fe deficiency
      in soybean include enhanced tricarboxylic acid cycle activity, enhanced
      activation of oxidative stress protection mechanisms and enhanced amino acid
      accumulation. Metabolites showing accumulation differences in Fe-starved but
      visually asymptomatic leaves could serve as biomarkers for early detection of Fe
      deficiency stress. 

PMID- 24738840
TI  - Nitrogen-rich and fire-resistant carbon aerogels for the removal of oil
      contaminants from water.
AB  - Effective removal of crude oils, petroleum products, organic solvents, and dyes
      from water is of significance in oceanography, environmental protection, and
      industrial production. Various techniques including physical and chemical
      absorption have been developed, but they suffer from problems such as low
      separation selectivity, a complicated and lengthy process, as well as high costs
      for reagents and devices. We present here a new material, termed nitrogen-rich
      carbon aerogels (NRC aerogels,) with highly porous structure and nitrogen-rich
      surfaces, exhibiting highly efficient separation of specific substances such as
      oils and organic pollutants. More importantly, we demonstrate that the fabricated
      NRC aerogels can also collect micrometer-sized oil droplets from an oil-water
      mixture with high efficiency that is well beyond what can be achieved by most
      existing separation methods, but is extremely important in practical marine oil
      spill recovery because a certain amount of oils often shears into many micrometer
      sized oil droplets by the sea wave, resulting in enormous potential destruction
      to marine ecosystem if not properly collected. Furthermore, our fabricated
      material can be used like a recyclable container for oils and chemicals cleanup
      because the oil/chemical-absorbed NRC aerogels can be readily cleaned for reuse
      by direct combustion in air because of their excellent hydrophobicity and fire
      resistant property. We demonstrate that they keep 61.2% absorption capacity even
      after 100 absorption/combustion cycles, which thus has the highest recyclability
      of the reported carbon aerogels. All these features make these fabricated NRC
      aerogels suitable for a wide range of applications in water purification and
      treatment. 

PMID- 24738839
TI  - Quantitative gingival crevicular fluid proteome in health and periodontal disease
      using stable isotope chemistries and mass spectrometry.
AB  - AIM: Application of quantitative stable isotope-labelling chemistries and mass
      spectrometry (MS) to determine alterations in gingival crevicular fluid (GCF)
      proteome in periodontal disease. MATERIAL AND METHODS: Quantitative proteome of
      GCF from 40 healthy individuals versus 40 patients with periodontal disease was
      established using 320 GCF samples and stable isotope-labelling reagents, ICAT and
      mTRAQ, with MS technology and validated by enzyme-linked immunosorbent methods.
      RESULTS: We have identified 238 distinct proteins of which 180 were quantified in
      GCF of both healthy and periodontal patients with additional 26 and 32 distinct
      proteins that were found only in GCF of healthy or periodontal patients. In
      addition, 42 pathogenic bacterial proteins and 11 yeast proteins were quantified.
      The data highlighted a series of proteins not quantified previously by large
      scale MS approaches in GCF with relevance to periodontal disease, such as host
      derived Ig alpha-2 chain C, Kallikrein-4, S100-A9, transmembrane proteinase 13,
      peptidase S1 domain, several collagen types and pathogenic bacterial proteins,
      e.g. formamidase, leucine aminopeptidase and virulence factor OMP85. CONCLUSIONS:
      The innovative analytical approaches provided detailed novel changes in both host
      and microbial derived GCF proteomes of periodontal patients. The study defined 50
      host and 16 pathogenic bacterial proteins significantly elevated in periodontal
      disease most of which were novel with significant potential for application in
      the clinical arena of periodontal disease.

PMID- 24738841
TI  - Cocaine use severity and cerebellar gray matter are associated with reversal
      learning deficits in cocaine-dependent individuals.
AB  - Cocaine addiction involves persistent deficits to unlearn previously rewarded
      response options, potentially due to neuroadaptations in learning-sensitive
      regions. Cocaine-targeted prefrontal systems have been consistently associated
      with reinforcement learning and reversal deficits, but more recent interspecies
      research has raised awareness about the contribution of the cerebellum to cocaine
      addiction and reversal. We aimed at investigating the link between cocaine use,
      reversal learning and prefrontal, insula and cerebellar gray matter in cocaine
      dependent individuals (CDIs) varying on levels of cocaine exposure in comparison
      with healthy controls (HCs). Twenty CDIs and 21 HCs performed a probabilistic
      reversal learning task (PRLT) and were subsequently scanned in a 3-Tesla magnetic
      resonance imaging scanner. In the PRLT, subjects progressively learn to respond
      to one predominantly reinforced stimulus, and then must learn to respond
      according to the opposite, previously irrelevant, stimulus-reward pairing.
      Performance measures were errors after reversal (reversal cost), and probability
      of maintaining response after errors. Voxel-based morphometry was conducted to
      investigate the association between gray matter volume in the regions of interest
      and cocaine use and PRLT performance. Severity of cocaine use correlated with
      gray matter volume reduction in the left cerebellum (lobule VIII), while greater
      reversal cost was correlated with gray matter volume reduction in a partially
      overlapping cluster (lobules VIIb and VIII). Right insula/inferior frontal gyrus
      correlated with probability of maintaining response after errors. Severity of
      cocaine use detrimentally impacted reversal learning and cerebellar gray matter. 

PMID- 24738842
TI  - Effect of Biodentine and Bioaggregate on odontoblastic differentiation via
      mitogen-activated protein kinase pathway in human dental pulp cells.
AB  - AIM: To compare the mineralization inductive capacity of Biodentine and
      Bioaggregate with Mineral trioxide aggregate (MTA) and to investigate possible
      signaling pathways of mineralization in human dental pulp cells (HDPCs).
      METHODOLOGY: Viability of HDPCs in response to Biodentine, Bioaggregate, and MTA
      was measured using 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyltetrazolium bromide.
      To investigate their potential to induce odontoblast differentiation, expression
      of dentine sialophosphoprotein (DSPP) and dentine matrix protein1 (DMP1) mRNA
      level was evaluated by RT-PCR. For the mineralized nodule assay, Alizarin red
      staining was performed. To determine the role of MAPK signaling in the
      odontoblastic differentiation of HDPCs, activated MAPKs were investigated by
      Western blot and the effect of MAPK inhibitor was examined by Alizarin red S
      staining. The results were statistically analysed using one-way anova and the
      Bonferroni test. RESULTS: The effects of MTA, Biodentine, and Bioaggregate on
      cell viability were similar. Biodentine and Bioaggregate enhanced DSPP and DMP1
      mRNA expression compared to the control group, but to the same extent as MTA (P <
      0.05). MTA, Biodentine, and Bioaggregate increased the area of calcified nodules
      compared to the control (P < 0.01). MTA, Biodentine, and Bioaggregate increased
      phosphorylation of extracellular signal-regulated kinase (ERK), p38, and c-Jun N
      terminal kinase (JNK). MAPK inhibitors attenuated mineralized nodule formation,
      which was increased by MTA, Biodentine, and Bioaggregate, respectively (P <
      0.01). CONCLUSION: Biodentine and Bioaggregate stimulated odontoblastic
      differentiation and mineralization nodule formation by activating the MAPK
      pathway as did MTA. This suggests that the new materials could be useful for
      regenerative endodontic procedures.

PMID- 24738843
TI  - Antibiotic resistance in acne: is it time to look beyond antibiotics and
      Propionobacterium acnes?

PMID- 24738844
TI  - Three-dimensional crystalline and homogeneous metallic nanostructures using
      directed assembly of nanoparticles.
AB  - Directed assembly of nano building blocks offers a versatile route to the
      creation of complex nanostructures with unique properties. Bottom-up directed
      assembly of nanoparticles have been considered as one of the best approaches to
      fabricate such functional and novel nanostructures. However, there is a dearth of
      studies on making crystalline, solid, and homogeneous nanostructures. This
      requires a fundamental understanding of the forces driving the assembly of
      nanoparticles and precise control of these forces to enable the formation of
      desired nanostructures. Here, we demonstrate that colloidal nanoparticles can be
      assembled and simultaneously fused into 3-D solid nanostructures in a single step
      using externally applied electric field. By understanding the influence of
      various assembly parameters, we showed the fabrication of 3-D metallic materials
      with complex geometries such as nanopillars, nanoboxes, and nanorings with
      feature sizes as small as 25 nm in less than a minute. The fabricated gold
      nanopillars have a polycrystalline nature, have an electrical resistivity that is
      lower than or equivalent to electroplated gold, and support strong plasmonic
      resonances. We also demonstrate that the fabrication process is versatile, as
      fast as electroplating, and scalable to the millimeter scale. These results
      indicate that the presented approach will facilitate fabrication of novel 3-D
      nanomaterials (homogeneous or hybrid) in an aqueous solution at room temperature
      and pressure, while addressing many of the manufacturing challenges in
      semiconductor nanoelectronics and nanophotonics. 

PMID- 24738847
TI  - Regulation of cardiomyocyte proliferation during development and regeneration.
AB  - The regulation of cardiomyocyte proliferation is important for heart development
      and regeneration. The proliferation patterns of cardiomyocytes are closely
      related to heart morphogenesis, size, and functions. The proliferation levels are
      high during early embryogenesis; however, mammalian cardiomyocytes exit the cell
      cycle irreversibly soon after birth. The cell cycle exit inhibits cardiac
      regeneration in mammals. On the other hand, cardiomyocytes of adult zebrafish and
      probably newts can proliferate after cardiac injury, and the hearts can be
      regenerated. Therefore, the ability to reproliferate determines regenerative
      ability. As in other cells, the relationship between proliferation and
      differentiation is very interesting, and is closely related to cardiac
      development, regeneration and homeostasis. In this review, these topics are
      discussed. 

PMID- 24738846
TI  - Barriers to hepatitis C antiviral therapy in HIV/HCV co-infected patients in the
      United States: a review.
AB  - This review synthesized the literature for barriers to HCV antiviral treatment in
      persons with HIV/HCV co-infection. Searches of PubMed, Embase, CINAHL, and Web of
      Science were conducted to identify relevant articles. Articles were excluded
      based on the following criteria: study conducted outside of the United States,
      not original research, pediatric study population, experimental study design, non
      HIV or non-HCV study population, and article published in a language other than
      English. Sixteen studies met criteria and varied widely in terms of study setting
      and design. Hepatic decompensation was the most commonly documented
      absolute/nonmodifiable medical barrier. Substance use was widely reported as a
      relative/modifiable medical barrier. Patient-level barriers included nonadherence
      to medical care, refusal of therapy, and social circumstances. Provider-level
      barriers included provider inexperience with antiviral treatment and/or
      reluctance of providers to refer patients for treatment. There are many ongoing
      challenges that are unique to managing this patient population effectively.
      Documenting and evaluating these obstacles are critical steps to managing and
      caring for these individuals in the future. In order to improve uptake of HCV
      therapy in persons with HIV/HCV co-infection, it is essential that barriers, both
      new and ongoing, are addressed, otherwise, treatment is of little benefit.

PMID- 24738848
TI  - Effects of long-term topical prostaglandin therapy on central corneal thickness.
AB  - PURPOSE: Recent studies have shown that prostaglandin analogues can decrease the
      central corneal thickness (CCT), however, most of those studies followed the
      patient's CCT for only approximately 2 years. The purpose of this present study
      was to perform a long-term follow-up investigation of CCT in patients who
      underwent only topical prostaglandin monotherapy over 4 years, and then analyze
      the CCT changes and the correlation between intraocular pressure (IOP) changes
      and CCT changes. METHODS: This retrospective study involved 52 eyes of 52
      glaucoma patients who consulted with glaucoma specialists at the Glaucoma Clinic
      of Kyoto Prefectural University of Medicine, Kyoto, Japan and underwent
      latanoprost eye drop monotherapy for more than 4 years in at least 1 eye between
      2005 and 2011. In all patients, CCT was evaluated by the Pentacam((r))
      Scheimpflug system at pretreatment, midpoint, and final follow-up. The Student's
      t-test was used to analyze the CCT changes. RESULTS: The mean CCT significantly
      decreased from 537 +/- 34 MUm at pretreatment to 526 +/- 32 MUm at the final
      follow-up (P<0.0001). Interestingly, no significant difference was found between
      the mean CCT at midpoint and that at final follow-up (P=0.17), yet the mean CCT
      significantly decreased to 529 +/- 32 MUm in the first 2 years (P=0.0015). No
      correlation was found between IOP and CCT reduction. CONCLUSIONS: The findings of
      this study show that latanoprost eye drops significantly reduce CCT during the
      initial stage of use, however, CCT reduction does not clinically affect IOP
      values.

PMID- 24738849
TI  - Immune regulation and anti-inflammatory effects of isogarcinol extracted from
      Garcinia mangostana L. against collagen-induced arthritis.
AB  - Isogarcinol is a natural compound that we extracted from Garcinia mangostana L.,
      and we were the first to report that it is a new immunosuppressant. In the
      present study, we investigated the immune regulation and anti-inflammatory
      effects of isogarcinol on collagen-induced arthritis (CIA) and explored its
      potential mechanism in the treatment of rheumatoid arthritis. The oral
      administration of isogarcinol significantly reduced clinical scores, alleviated
      cartilage and bone erosion, and reduced the levels of serum inflammatory
      cytokines in CIA mice. Isogarcinol inhibited xylene-induced mouse ear edema in
      vivo. In vitro, isogarcinol decreased iNOS and COX-2 mRNA expression and NO
      content by inhibiting NF-kappaB expression. Furthermore, isogarcinol decreased
      the activity of NFAT and inhibited IL-2 expression. The mechanism of action of
      isogarcinol is associated with down-regulation of both autoimmune and
      inflammatory reactions. 

PMID- 24738850
TI  - Peginterferon alpha in the treatment of chronic hepatitis B.
AB  - INTRODUCTION: Hepatitis B virus (HBV) infection is a global health problem.
      Peginterferon alpha (PEG-IFN), which includes PEG-IFN alpha-2a (Pegasys) and PEG
      IFN alpha-2b (Peg-Intron), can be used to treat patients with chronic hepatitis B
      (CHB) infection. A finite duration of PEG-IFN therapy may lead to long-term viral
      suppression. Clinically, it is important to identify super-responders and null
      responders to PEG-IFN due to its substantial side effects. AREAS COVERED: From
      the literature review, it is known that PEG-IFN is more effective for hepatitis B
      e antigen (HBeAg)-positive patients who have high pre-treatment alanine
      aminotransferase level, lower HBV DNA level and genotype A (vs genotype D), as
      well as those with more favourable viral predictors, such as precore stop codon
      or basal core promoter mutants infections in Asian patients and wild-type virus
      in Caucasian patients. For HBeAg-positive patients and HBeAg-negative patients
      with genotype D infection, PEG-IFN therapy could be terminated early at week 12
      or 24 in primary non-responders defined by the Hepatitis B surface antigen
      stopping rules. With regard to host factors, single nucleotide polymorphisms of
      IL28B do not seem to affect the treatment outcomes in Asian patients, but its
      role in Caucasian patients remains disputed. EXPERT OPINION: Most of the known
      predictors need validation by large prospective trials. In addition, we need to
      identify more baseline predictors for super-responders in order to achieve
      personalised PEG-IFN treatment for CHB.

PMID- 24738851
TI  - Global plant-responding mechanisms to salt stress: physiological and molecular
      levels and implications in biotechnology.
AB  - The increasing seriousness of salinization aggravates the food, population and
      environmental issues. Ameliorating the salt-resistance of plants especially the
      crops is the most effective measure to solve the worldwide problem. The salinity
      can cause damage to plants mainly from two aspects: hyperosmotic and hyperionic
      stresses leading to the restrain of growth and photosynthesis. To the adverse
      effects, the plants derive corresponding strategies including: ion regulation and
      compartmentalization, biosynthesis of compatible solutes, induction of
      antioxidant enzymes and plant hormones. With the development of molecular
      biology, our understanding of the molecular and physiology knowledge is becoming
      clearness. The complex signal transduction underlying the salt resistance is
      being illuminated brighter and clearer. The SOS pathway is the central of the
      cell signaling in salt stress. The accumulation of the compatible solutes and the
      activation of the antioxidant system are the effective measures for plants to
      enhance the salt resistance. How to make full use of our understanding to improve
      the output of crops is a huge challenge for us, yet the application of the
      genetic engineering makes this possible. In this review, we will discuss the
      influence of the salt stress and the response of the plants in detail expecting
      to provide a particular account for the plant resistance in molecular,
      physiological and transgenic fields. 

PMID- 24738853
TI  - Simultaneous detection of human mitochondrial DNA and nuclear-inserted
      mitochondrial-origin sequences (NumtS) using forensic mtDNA amplification
      strategies and pyrosequencing technology.
AB  - Next-generation sequencing technologies enable the identification of minor
      mitochondrial DNA variants with higher sensitivity than Sanger methods, allowing
      for enhanced identification of minor variants. In this study, mixtures of human
      mtDNA control region amplicons were subjected to pyrosequencing to determine the
      detection threshold of the Roche GS Junior((r)) instrument (Roche Applied
      Science, Indianapolis, IN). In addition to expected variants, a set of
      reproducible variants was consistently found in reads from one particular
      amplicon. A BLASTn search of the variant sequence revealed identity to a segment
      of a 611-bp nuclear insertion of the mitochondrial control region (NumtS)
      spanning the primer-binding sites of this amplicon (Nature 1995;378:489). Primers
      (Hum Genet 2012;131:757; Hum Biol 1996;68:847) flanking the insertion were used
      to confirm the presence or absence of the NumtS in buccal DNA extracts from
      twenty donors. These results further our understanding of human mtDNA variation
      and are expected to have a positive impact on the interpretation of mtDNA
      profiles using deep-sequencing methods in casework. 

PMID- 24738852
TI  - Probable transfusion-transmission of Anaplasma phagocytophilum by leukoreduced
      platelets.
AB  - BACKGROUND: Anaplasma phagocytophilum (AP), a tick-borne obligate intracellular
      bacterium, causes human granulocytic anaplasmosis (HGA) and has been implicated
      in seven transfusion-transmitted (TT)-HGA cases associated with red blood cells
      (RBCs). Here we report the first probable case of TT-HGA involving leukoreduced
      platelets (PLTs). CASE REPORT: A hospitalized male received 25 blood components
      (November 2012) before his death from trauma. Hospital testing confirmed HGA by
      peripheral blood smears; samples were also sent to IMUGEN, Inc. (Norwood, MA),
      for AP-polymerase chain reaction (PCR) and AP-immunoglobulin (Ig)M and IgG enzyme
      immunoassay. All 12 potentially transmitting donors provided follow-up samples.
      RESULTS: Recipient smears progressed from negative to predominantly positive 16
      days posttransfusion; hospital-performed AP-PCR was positive on Day 22. IMUGEN
      sample testing was PCR positive and IgM and IgG negative 14 to 23 days
      posttransfusion. The recipient had no known AP risk factors. One of 12 donors of
      RBCs or PLTs (leukoreduced 5-day-old PLTs) provided six follow-up samples; all
      were strongly IgG positive and IgM negative; one was PCR-positive. The IgG
      positive donor was a 52-year-old female from Hudson Valley, New York, an area
      endemic for AP. She reported tick bites in September to October 2012 with no
      travel outside New York. The donor remained asymptomatic and received no
      treatment. The cocomponent PLT unit was transfused to a 78-year-old male who died
      of causes unrelated to AP. CONCLUSIONS: This eighth case of probable TT-HGA
      indicates that leukoreduced PLTs may be infectious. An antibody- and PCR-positive
      donor having prior tick exposure living in an endemic area was identified. PCR
      positivity and elevated IgG levels, which continue to exceed the assay's
      detectible range even in the absence of IgM, indicate active donor infection.

PMID- 24738854
TI  - Organophosphate flame retardants in indoor dust from Egypt: implications for
      human exposure.
AB  - Organophosphate flame retardants (PFRs) have been proposed as alternatives for
      the phased out PBDE formulations. However, there exists no information on indoor
      dust contamination with PFRs in Africa. In this study, we report--for the first
      time--on levels and profiles of PFRs in dust samples from Egyptian houses (n =
      20), offices (n = 20), cars (n = 20), and public microenvironments (PMEs; n =
      11). Results revealed that PFR levels in Egyptian indoor dust are among the
      lowest reported worldwide. This may be attributed to less strict fire-safety
      standards and lack of regulatory actions against PBDEs. Triphenylphosphate was
      the only PFR detected in all samples with highest average concentration (386 ng
      g(-1)). While tris-2-chloroethyl phosphate, tris(1-chloro-2-propyl)phosphate and
      tris-1,3-dichloropropylphosphate showed higher detection frequency (DF = 69%,
      57%, and 56%; average = 233, 229, and 144 ng g(-1), respectively), tri(2
      butoxyexthyl)phosphate (37%; 294 ng g(-1)) displayed the second highest average
      concentration. Statistical analysis revealed significantly (P < 0.05) higher
      concentrations of SigmaPFRs in cars (average = 1011 ng g(-1)) and PMEs (2167 ng
      g(-1)) than in houses (310 ng g(-1)) and offices (450 ng g(-1)). Estimated
      exposures of adults and toddlers to PFRs via dust ingestion were much lower than
      the reported reference doses, indicating no immediate health risk to the Egyptian
      population.

PMID- 24738855
TI  - Fine tuning of lithographic masks through thin films of PS-b-PMMA with different
      molar mass by rapid thermal processing.
AB  - The self-assembly of asymmetric polystyrene-b-poly(methyl methacrylate) (PS-b
      PMMA) block copolymer based nanoporous thin films over a broad range of molar
      mass (Mn) between 39 kg.mol(-1) and 205 kg.mol(-1) is obtained by means of a
      simple thermal treatment. In the case of standard thermal treatments, the self
      assembly process of block copolymers is hindered at small Mn by thermodynamic
      limitations and by a large kinetic barrier at high Mn. We demonstrate that a fine
      tuning of the annealing parameters, performed by a Rapid Thermal Processing (RTP)
      machine, permits us to overcome those limitations. Cylindrical features are
      obtained by varying Mn and properly changing the corresponding annealing
      temperature, while keeping constant the annealing time (900 s), the film
      thickness (~30 nm), and the PS fraction (~0.7). The morphology, the
      characteristic dimensions (i.e., the pore diameter d and the pore-to-pore
      distance L0), and the order parameter (i.e., the lattice correlation length xi)
      of the samples are analyzed by scanning electron microscopy and grazing-incidence
      small-angle X-ray scattering, obtaining values of d ranging between 12 and 30 nm
      and L0 ranging between 24 and 73 nm. The dependence of L0 as a 0.67 power law of
      the number of segments places these systems inside the strong segregation limit
      regime. The experimental results evidence the capability to tailor the self
      assembly processes of block copolymers over a wide range of molecular weights by
      a simple thermal process, fully compatible with the stringent constraints of
      lithographic applications and industrial manufacturing. 

PMID- 24738856
TI  - Order-2 Stability Analysis of Particle Swarm Optimization.
AB  - Several stability analyses and stable regions of particle swarm optimization
      (PSO) have been proposed before. The assumption of stagnation and different
      definitions of stability are adopted in these analyses. In this paper, the order
      2 stability of PSO is analyzed based on a weak stagnation assumption. A new
      definition of stability is proposed and an order-2 stable region is obtained.
      Several existing stable analyses for canonical PSO are compared, especially their
      definitions of stability and the corresponding stable regions. It is shown that
      the classical stagnation assumption is too strict and not necessary. Moreover,
      among all these definitions of stability, it is shown that our definition
      requires the weakest conditions, and additional conditions bring no benefit.
      Finally, numerical experiments are reported to show that the obtained stable
      region is meaningful. A new parameter combination of PSO is also shown to be
      good, even better than some known best parameter combinations. 

PMID- 24738857
TI  - Geographic distribution and niche divergence of two stinkbugs, Parastrachia
      japonensis and Parastrachia nagaensis.
AB  - Parastrachiidae is a small stinkbug family containing only one genus and two
      species, Parastrachia japonensis (Scott) (Hemiptera: Heteroptera: Pentatomoidea)
      and Parastrachia nagaensis Distant. The geographic distribution of the genus has
      been poorly studied. Niche conservatism refers to that idea that closely related
      species are more ecologically similar than would be expected, whereas niche
      divergence predicts they occupy distinct niche spaces. The existence of only two
      species within one genus suggests niche conservatism or differentiation might
      exist among them. Herein, the distribution of the genus was mapped, potential
      distributions were predicted using ecological niche modeling, and climate spaces
      occupied by the two species were identified and compared. Our outlined map
      supports the general spreading route proposed by Schaefer et al. The potential
      distributions suggest that the genus' range could extend beyond its presently
      known distribution, and further investigation into this area could aid in their
      conservation, particularly P. nagaensis. The niche space inferred by ecological
      niche modeling suggests the two species do not occupy identical habitat, but the
      differences between their models could simply be due to the differential
      availability of habitat in the different regions that they occupy.

PMID- 24738858
TI  - A pragmatic belief system in family meaning-making after death.
AB  - The authors explored a sample of families' beliefs concerning creation of meaning
      in the recent death of the elderly husband and father and his existence in an
      afterlife. Data were collected through qualitative inquiry. Family members from
      34 families were asked about their reaction to their loved one's death. Three
      themes emerged from participants' responses (a) the significance of context in
      the father and husband's life and death; (b) family members' folk beliefs; and
      (c) recalling the after-death ritual. The themes interpenetrate at the point
      where family members, although doubtful, hoped their loved one continues in an
      afterlife. 

PMID- 24738859
TI  - Affinity-guided covalent conjugation reactions based on PDZ-peptide and SH3
      peptide interactions.
AB  - Specific protein-peptide interactions are prevalent in the living cells and form
      a tightly regulated signaling network. These interactions, many of which have
      structural information revealed, provide ideal templates for affinity-guided
      covalent bioconjugation. Here we report the development of a set of four new
      reactions that covalently and site-specifically link nonenzymatic scaffolding
      domains (two PDZ and two SH3 domains) and their ligands through thiol
      chloroacetyl SN2 reaction. Guided by the three-dimensional structure of the wild
      type complex, a selected position of the protein was mutated to cysteine, and at
      the same time, an alpha-chloroacetyl group was installed at a corresponding
      position of the peptide. Specific binding interaction between the two brings the
      reactive groups into close proximity, converts the nonreactive cysteine residue
      into a content-dependent reactive site, and induces the nucleophilic reaction
      that is inert in the absence of the binding event. The specificity,
      orthogonality, and modularity of the four reactions were characterized, the
      reaction was applied to label proteins in vitro and receptor on the surface of
      mammalian cells, and the system was utilized to assemble covalent protein
      complexes with unnatural geometries.

PMID- 24738860
TI  - Kanashibari : a ghost's business.

PMID- 24738861
TI  - Letter to the Editor: reexamining Penfield's Homunculus.
AB  - Snyder and Whitaker's (2013) discussion of Penfield's homunculus in a recent
      issue of this journal was stimulating but I believe mistaken in several ways.
      This letter clarifies the diagram's supposed ambiguity, highlights a largely
      overlooked problem with improper scaling and challenges the authors' argument for
      the superiority of the 1950 version of the image. 

PMID- 24738866
TI  - Ambient intermolecular [2 + 2] cycloaddition: an example of carbophilicity and
      oxophilicity competition in Au/Ag catalysis.
AB  - The gold-catalyzed intermolecular [2 + 2] cycloaddition of propargyl esters was
      achieved with good stereoselectivity. The "silver-free" condition was critical
      for this transformation, while only a trace amount of [2 + 2] products were
      formed in the presence of silver under otherwise identical conditions. 

PMID- 24738865
TI  - Netrin-1 induces MMP-12-dependent E-cadherin degradation via the distinct
      activation of PKCalpha and FAK/Fyn in promoting mesenchymal stem cell motility.
AB  - Netrin-1 (Ntn-1) is a potent inducer of neuronal cell migration; however, its
      molecular mechanism that guides the migratory behavior of stem cells has not been
      characterized. In this study, we investigate the role of Ntn-1 in promoting the
      motility of human umbilical cord blood-derived mesenchymal stem cells (UCB-MSCs)
      and its related signaling pathways. Ntn-1 (50 ng/mL) significantly increased
      motility of UCB-MSCs, which was inhibited by blocking antibodies for deleted in
      colorectal cancer (DCC) and integrin (IN) alpha6beta4. Ntn-1 in DCC stimulated
      protein kinase Calpha (PKCalpha) activation, but not PKCE, PKCtheta, and PKCzeta,
      while Ntn-1 in INalpha6beta4 induced the phosphorylation of focal adhesion kinase
      (FAK) and Fyn. Notably, Ntn-1 induced phosphorylation of extracellular signal
      regulated kinases (ERK), c-Jun N-terminal kinases (JNK), and nuclear factor kappa
      B (NF-kappaB), but they were concurrently downregulated by blocking the
      activities of PKCalpha, FAK, and Fyn. Ntn-1 uniquely increased the MMP-12
      expression of all the matrix metalloproteinase (MMP) isoforms present in UCB
      MSCs, though this was significantly blocked by an NF-kappaB inhibitor. Finally,
      Ntn-1 induced the MMP-12-dependent degradation of E-cadherin (E-cad), while Ntn-1
      abrogated the interaction between E-cad and p120-catenin. In addition, Ntn-1 has
      the ability to stimulate cytoskeletal reorganization-related proteins, such as
      Cdc42, Rac1, Profilin-1, Cofilin-1, alpha-Actinin-4, and filamentous actin (F
      actin) in UCB-MSCs. These results demonstrate that Ntn-1 induces MMP-12-dependent
      E-cad degradation via the distinct activation of PKCalpha and FAK/Fyn, which is
      necessary to govern the activation of ERK, JNK, and NF-kappaB in promoting
      motility of UCB-MSCs. 

PMID- 24738867
TI  - Lessons to be learnt in managing the breech presentation at term: an 11-year
      single-centre retrospective study.
AB  - BACKGROUND: The 2000 publication of the Term Breech Trial significantly impacted
      obstetric practice in Australia with a rapid increase in delivery of term breech
      singletons by caesarean section. More reassuring data from European centres who
      continued to offer vaginal breech deliveries to carefully selected women have led
      to a softening of international guidelines which now support an individualised
      approach to management. The application of this principle to an Australian
      population, particularly in the wake of such a major change in obstetric
      practice, has not previously been demonstrated. AIM: To compare short-term
      neonatal and maternal morbidity for infants with a singleton breech presentation
      born after 37 weeks, according to planned mode of delivery. MATERIALS AND
      METHODS: Eleven-year single-centre retrospective study with intention-to-treat
      analysis based on intended mode of delivery. RESULTS: Two hundred and forty-three
      of 766 (31.7%) eligible women elected for planned vaginal breech delivery. The
      overall success rate in this group was 58%. Morbidity rates were low and compare
      favourably with similar international studies. However, there was a
      nonsignificant trend towards higher rates of short-term serious neonatal and
      maternal morbidity in the planned vaginal delivery group (1.6 vs 0.4%, P = 0.08
      and 8.2 vs 4.8%, P = 0.06, respectively). CONCLUSIONS: Attempted vaginal delivery
      for breech presentation remains an option in carefully selected women under
      strict obstetric protocols.

PMID- 24738868
TI  - The catabolic enzyme methionine gamma-lyase limits methionine accumulation in
      potato tubers.
AB  - Increasing methionine in potato tubers is desirable, both to increase the
      availability of this limiting essential amino acid and to enhance the aroma of
      baked and fried potatoes. Previous attempts to elevate potato methionine content
      using transgenic approaches have focused on increasing methionine biosynthesis.
      Higher isoleucine accumulation in these transgenic tubers suggested that the
      potatoes compensate for increased methionine biosynthesis with enhanced
      catabolism via methionine gamma-lyase (MGL), thereby producing 2-ketybutyrate for
      isoleucine biosynthesis. In the current study, we show that potato StMGL1 encodes
      a functional MGL in potato tubers. In planta silencing of StMGL1 results in an
      increased methionine to isoleucine ratio in the free amino acid profile of potato
      tubers and, in some transgenic lines, elevated accumulation of free methionine.
      In both wild-type and transgenic tubers, the ratio of methionine to isoleucine is
      negatively correlated with the level of StMGL1 transcript. A three-dimensional
      distribution of free amino acids in potato tubers is also described. 

PMID- 24738869
TI  - Corroborating evidence-based medicine.
AB  - Proponents of evidence-based medicine (EBM) have argued convincingly for applying
      this scientific method to medicine. However, the current methodological framework
      of the EBM movement has recently been called into question, especially in
      epidemiology and the philosophy of science. The debate has focused on whether the
      methodology of randomized controlled trials provides the best evidence available.
      This paper attempts to shift the focus of the debate by arguing that clinical
      reasoning involves a patchwork of evidential approaches and that the emphasis on
      evidence hierarchies of methodology fails to lend credence to the common practice
      of corroboration in medicine. I argue that the strength of evidence lies in the
      evidence itself, and not the methodology used to obtain that evidence.
      Ultimately, when it comes to evaluating the effectiveness of medical
      interventions, it is the evidence obtained from the methodology rather than the
      methodology that should establish the strength of the evidence. 

PMID- 24738871
TI  - Darier's disease with cystic changes in the kidney.

PMID- 24738870
TI  - The periodontal health component of the Renal Impairment In Secondary Care
      (RIISC) cohort study: a description of the rationale, methodology and initial
      baseline results.
AB  - INTRODUCTION: Chronic kidney disease (CKD) is associated with significant
      morbidity and mortality. There is a need to identify novel and modifiable risk
      factors in such patients. The periodontal component of the Renal Impairment In
      Secondary Care (RIISC) study aims to evaluate the association between chronic
      periodontitis and CKD progression. METHODS: The RIISC study is a prospective,
      observational cohort study of patients with CKD from a renal clinic at a hospital
      in the West Midlands region of the UK. Patients undergo a periodontal examination
      and plaque and saliva sampling. To benchmark the oral health status of the RIISC
      cohort, we compared it to the Adult Dental Health Survey 2009 (ADHS), a
      representative survey of the oral health of community dwelling adults in the UK.
      RESULTS: Of the first 500 patients recruited into the RIISC study, 469 patients
      underwent a dental examination and 80 (17%) were edentulous. Among dentate
      subjects, patients within RIISC were significantly more likely to have any (OR
      4.0 95% CI 2.7-5.9) or severe (OR 3.8 95% CI 2.5-5.6) periodontitis compared to
      the ADHS sample. CONCLUSION: The prevalence and severity of chronic periodontitis
      in this cohort of CKD patients is markedly higher than a geographically matched
      control population.

PMID- 24738872
TI  - 3D structures and redox potentials of Cu2+-Abeta(1-16) complexes at different pH:
      a computational study.
AB  - Oxidative stress induced by redox-active metal cations such as Cu(2+) is a key
      event in the development of Alzheimer's disease. A detailed knowledge of the
      structure of Cu(2+)-Abeta complex is thus important to get a better understanding
      of this critical process. In the present study, we use a computational approach
      that combines homology modeling with quantum-mechanics-based methods to determine
      plausible 3D structures of Cu(2+)-Abeta(1-16) complexes that enclose the
      different metal coordination spheres proposed experimentally at different pH
      values. With these models in hand, we determine their standard reduction
      potential (SRP) with the aim of getting new insights into the relation between
      the structure of these complexes and their redox behavior. Results show that in
      all cases copper reduction induces CObackbone decoordination, which, for
      distorted square planar structures in the oxidized state (Ia_deltadelta,
      IIa_epsilondeltaepsilon, IIa_epsilonepsilonepsilon, and IIc_epsilon), leads to
      tricoordinated species. For the pentacoordinated structural candidate
      Ib_deltaepsilon with Glu11 at the apical position, the reduction leads to a
      distorted tetrahedral structure. The present results highlight the importance of
      the nature of the ligands on the SRP. The computed values (with respect to the
      standard hydrogen electrode) for complexes enclosing negatively charged ligands
      in the coordination sphere (from -0.81 to -0.12 V) are significantly lower than
      those computed for models involving neutral ligands (from 0.19 to 0.28 V). Major
      geometry changes induced by reduction, on both the metal site and the peptide
      configuration, are discussed as well as their possible influence in the formation
      of reactive oxygen species. 

PMID- 24738873
TI  - Transport and dispersion of nanoparticles in periodic nanopost arrays.
AB  - Nanoparticles transported through highly confined porous media exhibit faster
      breakthrough than small molecule tracers. Despite important technological
      applications in advanced materials, human health, energy, and environment, the
      microscale mechanisms leading to early breakthrough have not been identified.
      Here, we measure dispersion of nanoparticles at the single-particle scale in
      regular arrays of nanoposts and show that for highly confined flows of dilute
      suspensions of nanoparticles the longitudinal and transverse velocities exhibit
      distinct scaling behaviors. The distributions of transverse particle velocities
      become narrower and more non-Gaussian when the particles are strongly confined.
      As a result, the transverse dispersion of highly confined nanoparticles at low
      Peclet numbers is significantly less important than longitudinal dispersion,
      leading to early breakthrough. This finding suggests a fundamental mechanism by
      which to control dispersion and thereby improve efficacy of nanoparticles applied
      for advanced polymer nanocomposites, drug delivery, hydrocarbon production, and
      environmental remediation. 

PMID- 24738874
TI  - In vivo evidence of arterial wall inflammation in childhood varicella-zoster
      virus cerebral vasculopathy.

PMID- 24738876
TI  - Correlating molecular spectroscopy and molecular chemometrics to explore
      carbohydrate functional groups and utilization of coproducts from biofuel and
      biobrewing processing.
AB  - Dried distillers grains with solubles (DDGS) was coproducts from bioethanol and
      biobrewing industry. It was an excellent resource of protein and energy feedstuff
      in China. Conventional studies often focus on traditional nutritional profiles.
      To data, there is little research on molecular structure-nutrition interaction of
      carbohydrate in coproducts. In this study, five kinds of corn-grain based DDGS
      and two kinds of barley-grain based DDGS were collected from different
      manufactures in the north of China. They were coded as "1, 2, 3, 4, 5, 6, and 7",
      respectively. The primary purposes of this project were to investigate the
      molecular structure-nutrition interaction of carbohydrate in coproducts, in terms
      of (1) carbohydrate-related chemical composition and nutrient profiles, (2)
      predicted values for energy in coproducts for animal, and (3) in situ digestion
      of dry matter. The result showed that acid detergent fiber content in corn DDGS
      and barley DDGS had negative correlation with structural carbohydrate peak area,
      cellulose compounds, and carbohydrate component peaks (first, second, and total
      peak area), which were measured with molecular spectroscopy. The correlation
      between carbohydrate peak area (second and total) and digestible fiber (tdNDF)
      were negative. There were no correlation between carbohydrate spectral
      intensities and energy values, carbohydrate subfractions partitioned by CNCPS
      system, and in situ rumen degradation. The results indicate that carbohydrate
      spectral profiles (functional groups) are associated with the carbohydrate
      nutritive values in coproducts from biofuel and biobrewing processing. 

PMID- 24738877
TI  - Family study of a Swiss patient uncovered a novel genetic basis for the S-s
      U+(var) phenotype.
AB  - BACKGROUND: The rare S-s- phenotype is typically found in persons of African
      origin. Three genetic bases underlying this phenotype have been identified so
      far: a large deletion including the GYPB gene, which encodes the S and s
      antigens, and two mutations affecting GYPB splicing (commonly called "P2" and
      "NY"). The discovery of the S-s- phenotype in a Swiss patient prompted this
      study. STUDY DESIGN AND METHODS: The GYPB genotype of the patient was analyzed
      with Beadchip technology and Sanger sequencing. GYPB haplotype analysis was also
      carried out in the patient's family. A functional splicing assay was developed to
      determine the impact of the identified mutation on GYPB splicing. RESULTS: Sanger
      sequencing of GYPB in the patient indicated that she was homozygous for a GYPB*s
      allele carrying a novel mutation in the splice donor site of Intron 5
      (c.270+5G>A). Analysis of GYPB haplotypes in the patient's family revealed that
      she actually inherited this mutated GYPB*s allele from her mother of Swiss
      ancestry and a deleted GYPB allele from her father of Egyptian ancestry. Using a
      minigene-based splicing assay, we showed that GYPB mutation c.270+5G>A causes the
      skipping of Exon B5, as previously reported for the P2 mutation (c.270+5G>T).
      Consistently, the patient's red blood cells were found to be S-s-U+(var) .
      CONCLUSION: A novel GYPB mutation (c.270+5G>A) accounting for the S-s-U+(var)
      phenotype was identified. In contrast with P2 and NY mutations, which also drive
      this rare phenotype, this novel GYPB mutation inactivates a GYPB*s allele and
      does not appear to be of African origin.

PMID- 24738878
TI  - Fluoxetine: a case history of its discovery and preclinical development.
AB  - INTRODUCTION: Depression is a multifactorial mood disorder with a high prevalence
      worldwide. Until now, treatments for depression have focused on the inhibition of
      monoaminergic reuptake sites, which augment the bioavailability of monoamines in
      the CNS. Advances in drug discovery have widened the therapeutic options with the
      synthesis of so-called selective serotonin reuptake inhibitors (SSRIs), such as
      fluoxetine. AREAS COVERED: The aim of this case history is to describe and
      discuss the pharmacokinetic and pharmacodynamic profiles of fluoxetine, including
      its acute effects and the adaptive changes induced after long-term treatment.
      Furthermore, the authors review the effect of fluoxetine on neuroplasticity and
      adult neurogenesis. In addition, the article summarises the preclinical
      behavioural data available on fluoxetine's effects on depressive-like behaviour,
      anxiety and cognition as well as its effects on other diseases. Finally, the
      article describes the seminal studies validating the antidepressant effects of
      fluoxetine. EXPERT OPINION: Fluoxetine is the first selective SSRI that has a
      recognised clinical efficacy and safety profile. Since its discovery, other
      molecules that mimic its mechanism of action have been developed, commencing a
      new age in the treatment of depression. Fluoxetine has also demonstrated utility
      in the treatment of other disorders for which its prescription has now been
      approved.

PMID- 24738879
TI  - Inhibition enhancer of zeste homologue 2 promotes senescence and apoptosis
      induced by doxorubicin in p53 mutant gastric cancer cells.
AB  - OBJECTIVES: Enhancer of zeste homologue 2 (EZH2) is crucially involved in
      epigenetic silencing by acting as a histone methyltransferase. Although EZH2 is
      overexpressed in many cancers and is involved in malignant cell proliferation and
      invasion, the role of EZH2 in senescence induced by DNA damage has up to now
      remained largely unknown. In this study, we sought to explore the outcome of EZH2
      depletion along with exposure of doxorubicin (DOX), and related mechanisms, in
      gastric cancer cells. MATERIALS AND METHODS: Here, senescence induced by DNA
      damage was achieved in gastric cancer cells by DOX treatment. EZH2 was
      downregulated by transfection with siRNA or treated with (-)-epigallocatechin-3
      gallate, a targeted inhibitor. Senescence-associated beta galactosidase (SA-beta
      gal) and formation of senescence-associated heterochromatin foci were used to
      identify cell senescence. To investigate effects of EZH2 depletion on the cell
      cycle, apoptosis and proliferation, flow cytometry and MTT analysis were
      employed. Changes in p53-p21 axis activation were detected by Western blotting.
      RESULTS: We found that cell proliferative arrest caused by DOX could be promoted
      by EZH2 depletion. Mechanistically, EZH2 depletion not only worked in
      coordination with DNA damage during the progression of cell senescence but also
      promoted apoptosis in p53 mutant cells. However, it had no cooperative
      relationship with DOX in p53 wild-type cells. CONCLUSIONS: These data help
      unravel a crucial role for EZH2 in senescence and apoptosis in gastric cancer
      cells and that p53 genomic status was associated with different cell responses to
      EZH2 silencing.

PMID- 24738880
TI  - Fatal falls from height in Taiwan.
AB  - This study conducts an investigation of fatal falls from height, examines gender
      differences, and compares our findings with those of Western countries. We review
      deaths in Taiwan caused by falls from height that underwent forensic autopsy from
      1994 to 2010. Among the examined cases, 182 were suicide, 156 were accidents, and
      18 were homicides. Men who fell from greater heights had a lower probability of
      fatal head trauma (p = 0.045), and women exhibited a lower fatal head trauma rate
      when falling from heights of between 10 and 25 m in accident group (p = 0.003).
      There was no significant difference between cases of falling from greater and
      lower heights within the suicide group (p = 0.834). Psychiatric illness was only
      reported in 20.3% and 28.8% cases in suicide and accident groups. Only in male
      cases was the use of psychotropic substances higher in the suicide groups than in
      the accident groups (p = 0.047).

PMID- 24738881
TI  - The effects of temperature on the development of the moth Athetis lepigone, and a
      prediction of field occurrence.
AB  - Athetis lepigone (Moschler) (Lepidoptera: Noctuidae) is an important insect pest
      of corn crops in China. To determine the effect of temperature on A. lepigone
      growth, and to provide a forecasting model for this pest, the development and
      fecundity of A. lepigone under five different temperatures (18, 21, 24, 27, 30 
      degrees C) was investigated, and an experimental population life table was
      constructed based on the obtained results. The results showed that the duration
      of development of A. lepigone decreased as the temperature increased from 18 to
      30  degrees C. Approximately 95% of mature larvae stopped pupating at 18  degrees
      C, and about 70% of mature larvae stopped pupating at 21  degrees C. When the
      growth chamber temperature was above 24  degrees C, no growth arrest was
      observed. The results indicated that the optimum growth temperature of A.
      lepigone was about 26.47  degrees C. In this study, the highest survival rate,
      fecundity per female, and population index trend were observed when the
      temperature was set at 27  degrees C. The percentages of larvae that could spin
      cocoons after the 5th or 6th instar differed at the different temperatures. The
      developmental threshold temperatures for A. lepigone eggs, larvae, pre-pupae,
      pupae, preoviposition females, and the whole generation (i.e., egg to
      oviposition) were 11.03, 9.04, 15.08, 11.79, 11.63, and 10.84  degrees C,
      respectively, and their effective accumulative temperatures were 63.51, 339.42,
      30.04, 118.41, 35.06 and 574.08 degree-days, respectively. Based on the effective
      accumulative temperature law, this pest insect can have four generations in most
      of the Huang-Huai region of China, and two to three generations annually in some
      cold regions. Athetis lepigone may have four generations in the mid-southern part
      of Hebei Province. This prediction matches the field survey results.

PMID- 24738882
TI  - Assessing the antifouling properties of cold-spray metal embedment using loading
      density gradients of metal particles.
AB  - Particles of copper, bronze and zinc were embedded into a polymer using cold
      spray technology to produce loading density gradients of metal particles. The
      gradients were used to identify the species with the highest tolerance to the
      release of copper and zinc ions. The gradients also established the minimum
      effective release rates (MERRs) of copper and zinc ions needed to prevent the
      recruitment of fouling under field conditions. Watersipora sp. and Simplaria
      pseudomilitaris had the highest tolerances to the release of metal ions. Copper
      and bronze gradient tubes were similar in their MERRs of copper ions against
      Watersipora sp. (0.058 g m(-2) h(-1) and 0.054 g m(-2) h(-1), respectively) and
      against S. pseudomilitaris (0.030 g m(-2) h(-1) and 0.025 g m(-2) h(-1),
      respectively). Zinc was not an effective antifoulant, with failure within two
      weeks. In conclusion, cold-spray gradients were effective in determining MERRs
      and these outcomes provide the basis for the development of cold-spray surfaces
      with pre-determined life-spans using controlled MERRs.

PMID- 24738883
TI  - Efficacy, safety, and tolerability of preservative-free fixed combination of
      tafluprost 0.0015%/timolol 0.5% versus concomitant use of the ingredients.
AB  - PURPOSE: To compare efficacy, safety, and tolerability of the preservative-free
      fixed combination (FC) and non-fixed combination (NFC) of tafluprost 0.0015% and
      timolol 0.5% in patients with open-angle glaucoma or ocular hypertension.
      METHODS: This 6-month, prospective, randomized, double-masked, active-controlled,
      parallel group, multicenter phase III study was performed in patients with ocular
      hypertension and open-angle glaucoma with untreated intraocular pressure (IOP)
      >=23 and <=36 mmHg at baseline. RESULTS: Four hundred patients washed out from
      IOP-lowering medication were randomized, 201 received the FC, and 199 received
      the NFC. Mean time-wise IOP decreases from baseline ranged from -7.3 to -9.1 mmHg
      (29.6%-34.6%) in the FC and from -7.5 to -9.4 mmHg (30.7%-36.0%) in the NFC arm
      [per-protocol (PP) dataset, P<0.0001 compared with baseline for both groups]. At
      month 6, the estimated overall treatment difference (FC-NFC) was 0.308 mmHg (PP
      dataset, 95% confidence interval from -0.194 to 0.810 mmHg). An IOP decrease
      >=30% was achieved in 58.3% and 66.9% of the patients in the FC and NFC groups,
      respectively (PP dataset; P=0.105); an IOP decrease >=35% was achieved in 36.6%
      and 43.1% of patients in the FC and NFC groups, respectively (PP dataset;
      P=0.297). Patients with ocular adverse events were evenly distributed in both
      groups. The most common side effect, conjunctival/ocular hyperemia was found in
      8% and 5% of patients in the FC and NFC arms, respectively. CONCLUSIONS: All
      measures of IOP reduction for FC of preservative-free tafluprost/timolol were
      statistically and clinically significant and non-inferior to those of the NFC,
      throughout the 6-month study period.

PMID- 24738885
TI  - Insights into desmosome biology from inherited human skin disease and
      cardiocutaneous syndromes.
AB  - The importance of desmosomes in tissue homeostasis is highlighted by natural and
      engineered mutations in desmosomal genes, which compromise the skin or heart and
      in some instances both. Desmosomal gene mutations account for 45-50% of cases of
      arrhythmogenic right ventricular cardiomyopathy, and are mutated in an array of
      other disorders such as striate palmoplantar keratoderma, hypotrichosis with or
      without skin vesicles and lethal acantholytic epidermolysis bullosa. Recently, we
      reported loss-of-function mutations in the human ADAM17 gene, encoding for the
      'sheddase' ADAM17, a transmembrane protein which cleaves extracellular domains of
      substrate proteins including TNF-alpha, growth factors and desmoglein (DSG) 2.
      Patients present with cardiomyopathy and an inflammatory skin and bowel syndrome
      with defective DSG processing. In contrast, the dominantly inherited tylosis with
      oesophageal cancer appears to result from gain-of-function in ADAM17 due to
      increased processing via iRHOM2. This review discusses the heterogeneity of
      mutations in desmosomes and their regulatory proteins.

PMID- 24738884
TI  - Cell junctions in the specialized conduction system of the heart.
AB  - Anchoring cell junctions are integral in maintaining electro-mechanical coupling
      of ventricular working cardiomyocytes; however, their role in cardiomyocytes of
      the cardiac conduction system (CCS) remains less clear. Recent studies in genetic
      mouse models and humans highlight the appearance of these cell junctions
      alongside gap junctions in the CCS and also show that defects in these structures
      and their components are associated with conduction impairments in the CCS. Here
      we outline current evidence supporting an integral relationship between anchoring
      and gap junctions in the CCS. Specifically we focus on (1) molecular and
      ultrastructural evidence for cell-cell junctions in specialized cardiomyocytes of
      the CCS, (2) genetic mouse models specifically targeting cell-cell junction
      components in the heart which exhibit CCS conduction defects and (3) human
      clinical studies from patients with cell-cell junction-based diseases that
      exhibit CCS electrophysiological defects.

PMID- 24738886
TI  - Reducing emissions of persistent organic pollutants from a diesel engine by
      fueling with water-containing butanol diesel blends.
AB  - The manufacture of water-containing butanol diesel blends requires no excess
      dehydration and surfactant addition. Therefore, compared with the manufacture of
      conventional bio-alcohols, the energy consumption for the manufacture of water
      containing butanol diesel blends is reduced, and the costs are lowered. In this
      study, we verified that using water-containing butanol diesel blends not only
      solves the tradeoff problem between nitrogen oxides (NOx) and particulate matter
      emissions from diesel engines, but it also reduces the emissions of persistent
      organic pollutants (POPs), including polycyclic aromatic hydrocarbons,
      polychlorinated dibenzo-p-dioxins and dibenzofurans, polychlorinated biphenyls,
      polychlorinated diphenyl ethers, polybrominated dibenzo-p-dioxins and
      dibenzofurans, polybrominated biphenyls and polybrominated diphenyl ethers. After
      using blends of B2 with 10% and 20% water-containing butanol, the POP emission
      factors were decreased by amounts in the range of 22.6%-42.3% and 38.0%-65.5% on
      a mass basis, as well as 18.7%-78.1% and 51.0%-84.9% on a toxicity basis. The
      addition of water-containing butanol introduced a lower content of aromatic
      compounds and most importantly, lead to more complete combustion, thus resulting
      in a great reduction in the POP emissions. Not only did the self-provided oxygen
      of butanol promote complete oxidation but also the water content in butanol
      diesel blends could cause a microexplosion mechanism, which provided a better
      turbulence and well-mixed environment for complete combustion. 

PMID- 24738888
TI  - New acylphloroglucinol derivatives with diverse architectures from Hypericum
      henryi.
AB  - Hyphenrones A-F (1-6), six polycyclic polyprenylated acylphloroglucinol
      derivatives with four architectures including three unprecedented cores as
      exemplified by 1, 3, and 4, were isolated from Hypericum henryi. Compounds 3 and
      4 possess two unique 5/8/5 and 6/6/5/8/5 fused ring systems, respectively. Their
      absolute configurations were defined by experimental and calculated ECD of 4 and
      X-ray diffractions of 5 and 6, coupled with their putative biosynthetic origins.
      Three compounds exhibited interesting AChE inhibitory activities. 

PMID- 24738889
TI  - Ion specific effects in trivalent counterion induced surface and solution self
      assembly of the anionic surfactant sodium polyethylene glycol monododecyl ether
      sulfate.
AB  - The effect of different trivalent counterions, Al(3+), Cr(3+), Sc(3+), Gd(3+),
      and La(3+), on the surface adsorption and Al(3+), Cr(3+), and Sc(3+) for solution
      self-assembly of the anionic surfactant sodium polyethylene glycol monododecyl
      ether sulfate has been studied by neutron reflectivity and small angle neutron
      scattering. The strong binding and complexation between the trivalent counterions
      and the anionic surfactant result in significant micellar growth and the
      formation of surface multilayer structures at the air-water interface at
      relatively low counterion concentrations. Broadly similar surface and solution
      behaviors are observed for the different trivalent counterions. The evolution in
      the surface and solution structures in detail depends upon the nature of the
      counterion, its hydrated radius and its strength of binding. Exceptionally the
      addition of Cr(3+) counterions have a less pronounced effect. This is attributed
      to a greater reluctance for exchange within the primary hydration shell for
      Cr(3+) ions, which results in a shielding of the electrostatic interactions and a
      reduced surfactant-counterion binding. 

PMID- 24738887
TI  - Stable methylation at promoters distinguishes epiblast stem cells from embryonic
      stem cells and the in vivo epiblasts.
AB  - Embryonic Stem Cells (ESCs) and Epiblast Stem Cells (EpiSCs) are the in vitro
      representatives of naive and primed pluripotency, respectively. It is currently
      unclear how their epigenomes underpin the phenotypic and molecular
      characteristics of these distinct pluripotent states. Here, we performed a genome
      wide comparison of DNA methylation between ESCs and EpiSCs by MethylCap-Seq. We
      observe that promoters are preferential targets for methylation in EpiSC compared
      to ESCs, in particular high CpG island promoters. This is in line with
      upregulation of the de novo methyltransferases Dnmt3a1 and Dnmt3b in EpiSC, and
      downregulation of the demethylases Tet1 and Tet2. Remarkably, the observed DNA
      methylation signature is specific to EpiSCs and differs from that of their in
      vivo counterpart, the postimplantation epiblast. Using a subset of promoters that
      are differentially methylated, we show that DNA methylation is established within
      a few days during in vitro outgrowth of the epiblast, and also occurs when ESCs
      are converted to EpiSCs in vitro. Once established, this methylation is stable,
      as ES-like cells obtained by in vitro reversion of EpiSCs display an epigenetic
      memory that only extensive passaging and sub-cloning are able to almost
      completely erase. 

PMID- 24738890
TI  - Mandibular reconstruction using a calcium phosphate/polyethylene glycol hydrogel
      carrier with BMP-2.
AB  - AIM: To test the hypothesis that a synthetic hydroxyapatite/beta-tricalcium
      phosphate (HA/TCP) construct combined with polyethylene glycol (PEG) hydrogel
      including recombinant human bone morphogenetic proteins-2 (rhBMP-2) enhances new
      bone formation compared with bone morphogenetic proteins-2 (BMP-2) delivered
      using the HA/TCP construct alone. MATERIAL AND METHODS: Bilateral mandibular
      partial thickness 20 * 8 * 8 mm (L * W * H) alveolar defects were surgically
      created in the edentulated posterior mandible in 18 female minipigs. Randomized
      into two groups of nine animals each, the alveolar defects either received HA/TCP
      or HA/TCP/PEG with or without BMP-2 (105 MUg/defect) in contra-lateral sites
      using a split-mouth design. Primary outcome, bone density (%) within four regions
      of interest, was evaluated following a 4-week healing interval when the animals
      were killed for histometric analysis. RESULTS: Bone morphogenetic proteins-2
      loaded onto HA/TCP constructs significantly enhanced new bone formation compared
      with HA/TCP controls. Adding PEG apparently obstructed BMP-2 induced bone
      formation. CONCLUSION: Polyethylene glycol compromises the osteogenic effect of
      BMP-2.

PMID- 24738892
TI  - Induction of labour: does it increase the risk of cesarean delivery?

PMID- 24738893
TI  - The power of the MicroMort.

PMID- 24738894
TI  - Association and prediction of amniotic fluid measurements for adverse pregnancy
      outcome: systematic review and meta-analysis.
AB  - BACKGROUND: Measurements of amniotic fluid volume are used for pregnancy
      surveillance despite a lack of evidence for their predictive ability. OBJECTIVE:
      To evaluate the association and predictive value of ultrasound measurements of
      amniotic fluid volume for adverse pregnancy outcome. SEARCH STRATEGY: Electronic
      databases (inception to October 2011), reference lists, hand searching of
      journals, contact with experts. SELECTION CRITERIA: Studies comparing
      measurements of amniotic fluid volume with adverse outcome, excluding pre-labour
      ruptured membranes or congenital/structural anomalies. DATA COLLECTION: Data on
      study characteristics, design, quality. Random effects meta-analysis to estimate
      summary odds ratios (prognostic association) and summary sensitivity, specificity
      and likelihood ratios (predictive ability). MAIN RESULTS: Forty-three studies
      (244,493 fetuses) were included demonstrating a strong association between
      oligohydramnios (varying definitions) and birthweight <10th centile (summary odds
      ratio [OR] 6.31, 95% confidence interval [95% CI] 4.15-9.58; high-risk population
      [author definition] n = 6 studies, 28,510 fetuses), and mortality (neonatal death
      any population summary OR 8.72, 95% CI 2.43-31.26; n = 6 studies, 55,735 fetuses;
      and perinatal mortality high-risk population summary OR 11.54, 95% CI 4.05-32.9;
      n = 2 studies, 27;891 fetuses). There was a strong association between
      polyhydramnios (maximum pool depth >8 cm or amniotic fluid index >=25 cm) and
      birthweight >90th centile (OR 11.41, 95% CI 7.09-18.36; n = 1 study, 3960
      fetuses). Despite strong associations, predictive accuracy for perinatal outcome
      was poor. AUTHOR'S CONCLUSION: Current evidence suggests that oligohydramnios is
      strongly associated with being small for gestational age and mortality, and
      polyhydramnios with birthweight >90th centile. Despite strong associations with
      poor outcome, they do not accurately predict outcome risk for individuals.

PMID- 24738895
TI  - FOR: women should be free to opt for cosmetic genital surgery.

PMID- 24738896
TI  - FOR: cosmetic vulvar surgery is a safe and effective option for our patients.

PMID- 24738897
TI  - AGAINST: the social vulnerability and cultural view of women as sex objects needs
      to end.

PMID- 24738898
TI  - AGAINST: labiaplasty is an unnecessary cosmetic procedure.

PMID- 24738899
TI  - Transverse uterine fundal incision for placenta praevia with accreta.

PMID- 24738900
TI  - Authors' reply: transverse uterine fundal incision for placenta praevia with
      accreta.

PMID- 24738901
TI  - Transverse uterine fundal incision for anterior placenta praevia accreta: more
      harm than good?

PMID- 24738902
TI  - Authors' reply: transverse uterine fundal incision in placenta praevia with
      possible placenta accreta.

PMID- 24738903
TI  - Placenta praevia accreta.

PMID- 24738904
TI  - Authors' reply: placenta praevia accreta.

PMID- 24738905
TI  - A report from #BlueJC: fertility implications following the surgical management
      of postpartum haemorrhage.

PMID- 24738907
TI  - Characteristics of obstetric patients referred to intensive care in an Australian
      tertiary hospital.
AB  - BACKGROUND: The low mortality rate of 8.4 deaths per 100,000 women giving birth
      in Australia is well described; however, less is known about the spectrum of
      morbidity evident in pregnant and postpartum women admitted to an intensive care
      unit. AIM: A detailed description of the demographics, comorbidities, diagnoses
      and interventions of pregnant and postpartum women admitted to an Australian
      intensive care unit (ICU). MATERIALS AND METHODS: A retrospective observational
      study was conducted in a large metropolitan hospital co-located with a quaternary
      level maternity hospital. The participants were women admitted to intensive care
      between 1 January 2007 and 30 June 2009 who were pregnant at any gestational age,
      or within 6 weeks postpartum. RESULTS: Two hundred and forty-nine women were
      admitted to ICU within the study period constituting 19% of all ICU admissions.
      The main reasons for admission were hypertensive disease of pregnancy and
      obstetric haemorrhage. The median (range) age was 32 (17-51) years, and ICU
      duration was 32 (8-228) h. The median APACHE III-J severity of illness score was
      32 (8-80). Almost one-quarter of admissions could be classified as primarily
      observational. The most common interventions in ICU were invasive arterial
      pressure monitoring, central venous access with pressure monitoring and magnesium
      infusions. One-fifth of admissions were invasively ventilated. CONCLUSION: A
      substantial number of pregnant and postpartum women admitted to ICU did not
      receive interventions typical of other critical illness, such as mechanical
      ventilation, inotropes or renal replacement therapy. This confounds the use of an
      ICU admission as a measure of maternal morbidity.

PMID- 24738908
TI  - Spontaneous surface self-assembly in protein-surfactant mixtures: interactions
      between hydrophobin and ethoxylated polysorbate surfactants.
AB  - The synergistic interactions between certain ethoxylated polysorbate nonionic
      surfactants and the protein hydrophobin result in spontaneous self-assembly at
      the air-water interface to form layered surface structures. The surface
      structures are characterized using neutron reflectivity. The formation of the
      layered surface structures is promoted by the hydrophobic interaction between the
      polysorbate alkyl chain and the hydrophobic patch on the surface of the globular
      hydrophobin and the interaction between the ethoxylated sorbitan headgroup and
      hydrophilic regions of the protein. The range of the ethoxylated polysorbate
      concentrations over which the surface ordering occurs is a maximum for the more
      hydrophobic surfactant polyoxyethylene(8) sorbitan monostearate. The structures
      at the air-water interface are accompanied by a profound change in the wetting
      properties of the solution on hydrophobic substrates. In the absence of the
      polysorbate surfactant, hydrophobin wets a hydrophobic surface, whereas the
      hydrophobin/ethoxylated polysorbate mixtures where multilayer formation occurs
      result in a significant dewetting of hydrophobic surfaces. The spontaneous
      surface self-assembly for hydrophobin/ethoxylated polysorbate surfactant mixtures
      and the changes in surface wetting properties provide a different insight into
      protein-surfactant interactions and potential for manipulating surface and
      interfacial properties and protein surface behavior. 

PMID- 24738909
TI  - Cross-talk between probiotic lactobacilli and host immune system.
AB  - The mechanism by which probiotic lactobacilli affect the immune system is strain
      specific. As the immune system is a multicompartmental system, each strain has
      its way to interact with it and induce a visible and quantifiable effect. This
      review summarizes the interplay existing between the host immune system and
      probiotic lactobacilli, that is, with emphasis on lactobacilli as a prototype
      probiotic genus. Several aspects including the bacterial-host cross-talk with the
      mucosal and systemic immune system are presented, as well as short sections on
      the competing effect towards pathogenic bacteria and their uses as delivery
      vehicle for antigens. 

PMID- 24738910
TI  - Cost-efficacy of biologic therapies for moderate to severe psoriasis from the
      perspective of the Taiwanese healthcare system.
AB  - BACKGROUND: Biologic therapies are more effective than conventional therapies in
      the treatment of psoriasis, but they are also more costly. OBJECTIVES: The aim of
      this study was to compare the cost-efficacy of etanercept, adalimumab, and
      ustekinumab therapies in the treatment of moderate to severe psoriasis in a
      Taiwanese setting. METHODS: We conducted a meta-analysis of randomized, placebo
      controlled trials to calculate the incremental efficacy of etanercept,
      adalimumab, and ustekinumab, respectively, in affecting a reduction of >=75% in
      score on the Psoriasis Area and Severity Index (PASI 75). The base, best case,
      and worst case incremental cost-effectiveness ratios (ICERs) for one subject to
      achieve PASI 75 were calculated for the purposes of economic analysis. RESULTS:
      One-year ICERs per PASI 75 responder were US$ 39,709 (best scenario US$ 36,400;
      worst scenario US$ 43,680), US$ 23,711 (best scenario US$ 22,633; worst scenario
      US$ 25,319), and US$ 26,329 (best scenario US$ 24,780; worst scenario US$ 27,623)
      for etanercept, adalimumab, and ustekinumab, respectively. Two year ICERs per
      PASI 75 responder were US$ 71,973 (best scenario US$ 65,975; worst scenario US$
      79,170), US$ 62,665 (best scenario US$ 59,817; worst scenario US$ 66,914), and
      US$ 52,657 (best scenario US$ 49,560; worst scenario US$ 55,427) for etanercept,
      adalimumab, and ustekinumab, respectively. CONCLUSIONS: In a Taiwanese setting,
      adalimumab and ustekinumab had lower 1-year costs per PASI 75 responder than
      etanercept, and ustekinumab had the lowest 2-year cost per PASI 75 responder.

PMID- 24738911
TI  - Biologically derived soft conducting hydrogels using heparin-doped polymer
      networks.
AB  - The emergence of flexible and stretchable electronic components expands the range
      of applications of electronic devices. Flexible devices are ideally suited for
      electronic biointerfaces because of mechanically permissive structures that
      conform to curvilinear structures found in native tissue. Most electronic
      materials used in these applications exhibit elastic moduli on the order of 0.1-1
      MPa. However, many electronically excitable tissues exhibit elasticities in the
      range of 1-10 kPa, several orders of magnitude smaller than existing components
      used in flexible devices. This work describes the use of biologically derived
      heparins as scaffold materials for fabricating networks with hybrid
      electronic/ionic conductivity and ultracompliant mechanical properties. Photo
      cross-linkable heparin-methacrylate hydrogels serve as templates to control the
      microstructure and doping of in situ polymerized polyaniline structures.
      Macroscopic heparin-doped polyaniline hydrogel dual networks exhibit impedances
      as low as Z = 4.17 Omega at 1 kHz and storage moduli of G' = 900 +/- 100 Pa. The
      conductivity of heparin/polyaniline networks depends on the oxidation state and
      microstructure of secondary polyaniline networks. Furthermore,
      heparin/polyaniline networks support the attachment, proliferation, and
      differentiation of murine myoblasts without any surface treatments. Taken
      together, these results suggest that heparin/polyaniline hydrogel networks
      exhibit suitable physical properties as an electronically active biointerface
      material that can match the mechanical properties of soft tissues composed of
      excitable cells. 

PMID- 24738912
TI  - Whisker-related circuitry in the trigeminal nucleus principalis: ultrastructure.
AB  - Trigeminal (V) nucleus principalis (PrV) is the requisite brainstem nucleus in
      the whisker-to-barrel cortex model system that is widely used to reveal
      mechanisms of map formation and information processing. Yet, little is known of
      the actual PrV circuitry. In the ventral "barrelette" portion of the adult mouse
      PrV, relationships between V primary afferent terminals, thalamic-projecting PrV
      neurons, and gamma-aminobutyric acid (GABA)-ergic terminals were analyzed in the
      electron microscope. Primary afferents, thalamic-projecting cells, and GABAergic
      terminals were labeled, respectively, by Neurobiotin injections in the V
      ganglion, horseradish peroxidase injections in the thalamus, and postembedding
      immunogold histochemistry. Primary afferent terminals (Neurobiotin- and glutamate
      immunoreactive) display asymmetric and multiple synapses predominantly upon the
      distal dendrites and spines of PrV cells that project to the thalamus. Primary
      afferents also synapse upon GABAergic terminals. GABAergic terminals display
      symmetric synapses onto primary afferent terminals, the somata and dendrites
      (distal, mostly) of thalamic-projecting neurons, and GABAergic dendrites. Thus,
      primary afferent inputs through the PrV are subject to pre- and postsynaptic
      GABAergic influences. As such, circuitry exists in PrV "barrelettes" for primary
      afferents to directly activate thalamic-projecting and inhibitory local circuit
      cells. The latter are synaptically associated with themselves, the primary
      afferents, and with the thalamic-projecting neurons. Thus, whisker-related
      primary afferent inputs through PrV projection neurons are pre- and
      postsynaptically modulated by local circuits.

PMID- 24738913
TI  - The risk/benefit of predicting a post-antibiotic era: is the alarm working?
AB  - There have been concerns about antimicrobial resistance since the first
      widespread use of antibiotics in humans. More recently, this concern has grown
      and become the focus of clinical, scientific, and political activity. In part,
      the political interest is a consequence of publicizing a bleak picture of a post
      antibiotic world. There are, however, dangers in using a discourse of fear. In
      this article, we discuss whether the evidence base is available to justify such
      claims and, more importantly, put this in the policy context with which it is
      used. Many governments now use a risk assessment approach to identify security
      concerns, based on reasonable worst-case scenarios. There is no doubt that for
      effective policy-based action to occur, antimicrobial resistance needs to be seen
      as a national and international security priority, particularly as the major cost
      of inaction will mostly be felt in the future. We conclude that presenting the
      evidence in a manner that is used to encourage prioritization of security policy
      is not only justified, it is essential to drive action in this area. 

PMID- 24738915
TI  - The impact of copper-containing and levonorgestrel-releasing intrauterine
      contraceptives on cervicovaginal cytology and microbiological flora: a
      prospective study.
AB  - OBJECTIVE: To compare vaginal microflora and cervical cytology before and after
      insertion of a copper-containing intrauterine device (Cu-IUD) or a levonorgestrel
      releasing-intrauterine system (LNG-IUS). METHODS: Between April 2009 and February
      2011, all women requesting insertion of an intrauterine contraceptive for family
      planning or noncontraceptive indications were enrolled. One hundred and eight Cu
      IUDs and 42 LNG-IUSs were placed. Cervical cytological and vaginal
      microbiological findings before insertion and after 12 months were recorded.
      RESULTS: With regard to cervical cytology, nonspecific inflammatory changes
      became more frequent (but not significantly so; p = 0.062) after one year of use
      of a Cu-IUD, whereas their prevalence remained unchanged among women fitted with
      a LNG-IUS. Colonisation by Candida spp. and mycoplasma infections were diagnosed
      significantly more often after one year of use of the Cu-IUD than at baseline.
      During the study period, women wearing a Cu-IUD complained significantly more
      frequently of vaginal discharge, pelvic pain, and increased menstrual flow.
      CONCLUSION: Use of a Cu-IUD - but not that of a LNG-IUS - was associated with an
      alteration of the vaginal flora and showed a trend towards a higher frequency of
      nonspecific inflammatory changes affecting cervical cytology.

PMID- 24738916
TI  - Designing quantitative structure activity relationships to predict specific toxic
      endpoints for polybrominated diphenyl ethers in mammalian cells.
AB  - Polybrominated diphenyl ethers (PBDEs) are known as effective flame retardants
      and have vast industrial application in products like plastics, building
      materials and textiles. They are found to be structurally similar to thyroid
      hormones that are responsible for regulating metabolism in the body. Structural
      similarity with the hormones poses a threat to human health because, once in the
      system, PBDEs have the potential to affect thyroid hormone transport and
      metabolism. This study was aimed at designing quantitative structure-activity
      relationship (QSAR) models for predicting toxic endpoints, namely cell viability
      and apoptosis, elicited by PBDEs in mammalian cells. Cell viability was evaluated
      quantitatively using a general cytotoxicity bioassay using Janus Green dye and
      apoptosis was evaluated using a caspase assay. This study has thus modelled the
      overall cytotoxic influence of PBDEs at an early and a late endpoint by the
      Genetic Function Approximation method. This research was a twofold process
      including running in vitro bioassays to collect data on the toxic endpoints and
      modeling the evaluated endpoints using QSARs. Cell viability and apoptosis
      responses for Hep G2 cells exposed to PBDEs were successfully modelled with an
      r(2) of 0.97 and 0.94, respectively. 

PMID- 24738914
TI  - Predictors, indicators, and validated measures of dependence in menthol smokers.
AB  - This article presents a comprehensive review of the menthol cigarette dependence
      related literature and results from an original analysis of the Total Exposure
      Study (TES), which included 1,100 menthol and 2,400 nonmenthol adult smokers. The
      substantial scientific evidence available related to age of first cigarette, age
      of regular use, single-item dependence indicators (smoking frequency, cigarettes
      per day, time to first cigarette, night waking to smoke), smoking duration,
      numerous validated and widely accepted measures of nicotine/cigarette dependence,
      and our analysis of the TES do not support that menthol smokers are more
      dependent than nonmenthol smokers or that menthol increases dependence. 

PMID- 24738917
TI  - Diacetyl: occurrence, analysis, and toxicity.
AB  - Diacetyl possesses a butter-like flavor and has been widely used as a flavoring
      agent. It forms from sugars and lipids via various bacteria and heat treatment in
      various foods and beverages, such as milk. The toxicity of diacetyl, especially
      when inhaled, has recently attracted the attention not only of consumers but also
      of regulatory agencies. Even though accurate quantitative analysis of diacetyl is
      extremely important in evaluating its possible adverse effects, precise
      quantitative analysis of diacetyl in foods and beverages, as well as in ambient
      air, is considerably difficult because it is highly reactive and soluble in
      water. Among the many analytical methods developed for measuring diacetyl,
      preparation of 2,3-dimethylquinoxaline followed by gas chromatography has been
      most commonly used in the analysis of various foods, beverages, and air samples.
      This mini-review summarizes the formation mechanisms, analytical methods,
      occurrence, and toxicity of diacetyl. 

PMID- 24738918
TI  - Structures of darunavir-resistant HIV-1 protease mutant reveal atypical binding
      of darunavir to wide open flaps.
AB  - The molecular basis for high resistance to clinical inhibitors of HIV-1 protease
      (PR) was examined for the variant designated PRP51 that was selected for
      resistance to darunavir (DRV). High resolution crystal structures of PRP51 with
      the active site D25N mutation revealed a ligand-free form and an inhibitor-bound
      form showing a unique binding site and orientation for DRV. This inactivating
      mutation is known to increase the dimer dissociation constant and decrease DRV
      affinity of PR. The PRP51-D25N dimers were in the open conformation with widely
      separated flaps, as reported for other highly resistant variants. PRP51-D25N
      dimer bound two DRV molecules and showed larger separation of 8.7 A between the
      closest atoms of the two flaps compared with 4.4 A for the ligand-free structure
      of this mutant. The ligand-free structure, however, lacked van der Waals contacts
      between Ile50 and Pro81' from the other subunit in the dimer, unlike the majority
      of PR structures. DRV is bound inside the active site cavity; however, the
      inhibitor is oriented almost perpendicular to its typical position and exhibits
      only 2 direct hydrogen bond and two water-mediated interactions with atoms of
      PRP51-D25N compared with 11 hydrogen bond interactions seen for DRV bound in the
      typical position in wild-type enzyme. The atypical location of DRV may provide
      opportunities for design of novel inhibitors targeting the open conformation of
      PR drug-resistant mutants.

PMID- 24738919
TI  - Unusual 4p16.3 deletions suggest an additional chromosome region for the Wolf
      Hirschhorn syndrome-associated seizures disorder.
AB  - OBJECTIVE: Seizure disorder is one of the most relevant clinical manifestations
      in Wolf-Hirschhorn syndrome (WHS) and it acts as independent prognostic factor
      for the severity of intellectual disability (ID). LETM1, encoding a mitochondrial
      protein playing a role in K(+) /H(+) exchange and in Ca(2+) homeostasis, is
      currently considered the major candidate gene. However, whether
      haploinsufficiency limited to LETM1 is enough to cause epilepsy is still unclear.
      The main purpose of the present research is to define the 4p chromosome regions
      where genes for seizures reside. METHODS: Comparison of our three unusual 4p16.3
      deletions with 13 literature reports. Array-comparative genomic hybridization (a
      CGH). Real-time polymerase chain reaction (RT-PCR) on messanger RNA (mRNA) of
      LETM1 and CPLX1. Direct sequencing of LETM1. RESULTS: Three unusual 4p16.3
      deletions were detected by array-CGH in absence of a obvious clinical diagnosis
      of WHS. Two of these, encompassing LETM1, were found in subjects who never had
      seizures. The deletions were interstitial, spanning 1.1 Mb with preservation of
      the terminal 1.77 Mb region in one case and 0.84 Mb with preservation of the
      terminal 1.07 Mb region in the other. The other deletion was terminal, affecting
      a 0.564 Mb segment, with preservation of LETM1, and it was associated with
      seizures and learning difficulties. Upon evaluating our patients along with
      literature reports, we noted that six of eight subjects with terminal 4p
      deletions preserving LETM1 had seizures, whereas seven of seven with interstitial
      deletions including LETM1 and preserving the terminal 1 Mb region on 4p did not.
      An additional chromosome region for seizures is suggested, falling within the
      terminal 1.5 Mb on 4p, not including LETM1. SIGNIFICANCE: We consider that
      haploinsufficiency not limited to LETM1 but including other genes acts as a risk
      factor for the WHS-associated seizure disorder, according to a comorbidity model
      of pathogenesis. Additional candidate genes reside in the terminal 1.5 Mb region
      on 4p, most likely distal to LETM1. A PowerPoint slide summarizing this article
      is available for download in the Supporting Information section here.

PMID- 24738921
TI  - The effect of floral resources on parasitoid and host longevity: prospects for
      conservation biological control in strawberries.
AB  - The strawberry tortricid, Acleris comariana Lienig and Zeller (Lepidoptera:
      Tortricidae) is an important pest in Danish strawberry production. Its most
      common parasitoid is Copidosoma aretas (Walker) (Hymenoptera: Chalcidoidea:
      Encyrtidae). To identify selective flowering plants that could be used to
      increase functional biodiversity, the longevity of C. aretas and its host A.
      comariana was assessed on 5 flowering species: buckwheat, Fagopyrum esculentum
      Moench (Caryophyllales: Polygonaceae); borage, Borago officinalis L.
      (Boraginaceae); strawberry, Fragaria x ananassa Duchesne (Rosales: Rosaceae);
      phacelia, Phacelia tanacetifolia Bentham (Boraginaceae); and dill, Anethum
      graveolens L. (Apiales: Apiaceae). Dill was only tested with C. aretas. Sucrose
      and pollen served as positive controls, and pure water as a negative control. In
      a subsequent field experiment, A. comariana larval density was assessed at 1, 6,
      and 11 m distances from buckwheat flower strips in 3 fields. The proportion of
      field-collected larvae that were parasitized by C. aretas or fungi was assessed.
      Among the tested floral diets, buckwheat was superior for C. aretas, increasing
      its longevity by 1.4 times compared to water. Although buckwheat also increased
      longevity of A. comariana, its longevity and survival on buckwheat, borage, and
      strawberry was not significantly different, so buckwheat was chosen for field
      experiments. A. comariana densities in the 3 fields with sown buckwheat flower
      strips were 0.5, 4.0, and 8.3 larvae per m per row of strawberry respectively. Of
      the collected larvae, a total of 1%, 39%, and 65% were parasitized by C. aretas,
      respectively. The density of A. comariana and the proportion parasitized by C.
      aretas were highly significantly correlated. Distance from floral strips had no
      significant effect on either A. comariana larval density or on the proportion of
      individuals parasitized by C. aretas. Few other parasitoids emerged from
      collected larvae, and no larvae were infected by entomopathogenic fungi. Still,
      total A. comariana mortality was significantly affected by distance to flower
      strips, with the highest mortality near the flower strips. As no effect of
      buckwheat flower strips on C. aretas parasitism was found, the positive effect
      they had on A. comariana control stems from unknown mortality factors. As
      literature indicates that buckwheat for flower strips can augment a more complex
      suite of natural enemies, one such mortality factor could be a non-consumptive
      predator and/or parasitoid effect, but this requires further study. If confirmed,
      buckwheat may be utilized together with a selective food plant, once identified.

PMID- 24738920
TI  - IL-10 function, regulation, and in bacterial keratitis.
AB  - The immune system protects the host from pathogenic microbes, but tight
      regulation of the evoked response is requisite to limit bystander damage. The
      interleukin (IL)-10 family of cytokines, composed of 9 members: IL-10, IL-19, IL
      20, IL-22, IL-24, IL-26, and 3 distantly related members, IL-28A, IL-28B, and IL
      29, plays a central role in this regulation. IL-10 family cytokines emerged
      before the adaptive immune response and elicit diverse host defense mechanisms,
      especially from epithelial cells during an infection. IL-10 family cytokines are
      also essential for maintenance and integrity of tissue epithelial layers. These
      cytokines promote innate immune responses from tissue epithelia that limit the
      damage caused by both viral and bacterial infections. They also facilitate tissue
      healing after infection/inflammation. In this regard, IL-10 suppresses pro
      inflammatory responses, limiting tissue disruption resulting from an inflammatory
      response. Thus, a central functional theme of IL-10 family cytokines is their
      role in tissue protection. This review focuses on IL-10, the founding member of
      this family of cytokines, and integrates recent data on the function and
      regulation of IL-10 during bacterial infections. Emphasis is placed on the role
      of IL-10 in Pseudomonas aeruginosa keratitis and the subsequent
      infectious/inflammatory processes evoked.

PMID- 24738922
TI  - DDIT3 overexpression increases odontoblastic potential of human dental pulp
      cells.
AB  - OBJECTIVES: Human dental pulp cells (HDPCs) with multi-potential
      differentiational capacity can undergo odontoblastic differentiation when
      stimulated with proinflammatory cytokines. However, factors linking
      proinflammatory stimuli and their odontoblastic differentiation have, as yet, not
      been completely understood. As an apoptotic transcription factor, DDIT3 plays a
      crucial role in the inflammatory reaction and in osteogenic differentiation.
      Thus, we hypothesized that DDIT3 may participate in odontoblastic differentiation
      of HDPCs. MATERIALS AND METHODS: Immunofluorescent staining was used to detect
      expression of DDIT3 in HDPCs and effects of TNFalpha, on its nuclear
      accumulation. HDPCs that overexpressed DDIT3 were developed and their
      proliferation and odontoblastic differentiation abilities were examined. qRT-PCR
      was employed to detect mineralization-related genes, including ALP, runt-related
      transcription factor-2 (Runx2), osterix (OSX), dentin sialophosphoprotein (DSPP),
      dentin matrix acidic phosphoprotein 1 (DMP1) and osteocalcin (OCN). Western blot
      analysis was performed to detect expression of DSPP protein. RESULTS: DDIT3 was
      expressed in HDPCs. TNFalpha treatment enhanced mRNA expression as well as
      nuclear accumulation of DDIT3 (slightly). DDIT3 overexpression reduced HDPC
      proliferation, however, it increased their calcium nodule formation and
      expression of OSX, DSPP, DMP1 and OCN. CONCLUSIONS: DDIT3 may be a factor that
      links proinflammatory stimuli and differentiation of HDPCs.

PMID- 24738924
TI  - Facile fabrication of magnetic carbon composites from hydrochar via simultaneous
      activation and magnetization for triclosan adsorption.
AB  - Advanced magnetic carbon composites with high specific surface area and high
      microporosity are required for both environmentally and agriculturally related
      applications. However, more research is needed for the development of a facile
      and highly efficient synthesis process. In the present work, a novel approach of
      simultaneous activation and magnetization is proposed for the fabrication of
      magnetic carbon composites via the thermal pyrolysis of hydrochar (i.e., a solid
      residue from a hydrothermal carbonization process) that has been pretreated with
      mixtures of ferric chloride (FeCl3) and zinc chloride (ZnCl2). The main objective
      of this study is the investigation of the variation of characteristics of
      magnetic carbon composites produced at various conditions, as well as triclosan
      (TCS) adsorption behavior on such composites. This presented simple one-step
      synthesis method has the following advantages: (a) the hydrochar is activated
      with high surface area and pore volume (up to 1351 m(2)/g and 0.549 cm(3)/g,
      respectively), (b) activation and magnetization are simultaneously achieved
      without further modification, (c) the magnetic particles (gamma-Fe2O3) are stable
      under an acidic medium (pH of 3.0 and 4.0), and (d) the products have the
      potential to remove TCS from aqueous solutions with a maximum adsorption capacity
      of 892.9 mg/g. The results indicate the effectiveness of this facile synthesis
      strategy in converting low-value biowaste into a functional material with high
      performance for pollutant removal from aqueous solutions. 

PMID- 24738925
TI  - Cucurbiturils substituted on the methylene bridge.
AB  - Cucurbit[6]uril (CB[6]) with a substituent attached solely to one methylene
      bridge was prepared for the first time. The monosubstituted CB[6] undergoes self
      assembly to form a cyclic tetramer in the solid state. The affinity of the
      monosubstituted CB[6] to a series of alkylammonium salts was measured revealing a
      minor effect of the substituent on the binding properties of the macrocycle. 

PMID- 24738926
TI  - Multiple discriminations experienced by people living with HIV in France: results
      from the ANRS-Vespa2 study.
AB  - Since the advent of AIDS, discrimination has remained at the core of the
      experience of people living with HIV (PLHIV). PLHIV who belong to minority groups
      are exposed to discrimination not only on the grounds of their HIV infection but
      also because of rejecting attitudes towards drug users, homosexuals and black
      people. This article aimed to measure the frequency of discrimination and assess
      its correlates among PLHIV in France. We used data from a national representative
      survey, the ANRS-Vespa2 study, conducted in France in 2011 among 3022 male and
      female HIV-positive patients followed at hospitals. Respondents answered a face
      to-face questionnaire documenting their health status and living conditions.
      Discrimination was documented during the previous two years on the grounds of HIV
      infection, gender, country of birth, skin colour, sexual orientation, place of
      residence, and substance abuse in a variety of contexts. For each context, we
      performed logistic regressions on discrimination, controlling for socio
      epidemiological group, age, education level and employment status. Discrimination
      is frequently experienced by PLHIV in France (26%), particularly when applying
      for a job (24%), interacting with family (11%) or seeking health services (8%).
      Women from sub-Saharan Africa reported the highest levels of discrimination,
      whereas heterosexual non-African men reported the lowest. Men who have sex with
      men experienced levels of discrimination that fell between those of these two
      groups. The major perceived reason for discrimination was HIV status (13%).
      Nationality, skin colour and sexual orientation were cited by 5% each, whereas
      gender was cited by 1% of respondents. Our analyses show that discrimination is a
      frequent and cross-cutting experience with differences across the various
      contexts and among the diverse subpopulations. The intertwining of HIV-related
      stigma with sexism, racism and homophobia needs to be addressed to understand why
      discrimination against PLHIV persists when the disease itself has greatly
      evolved. 

PMID- 24738927
TI  - Both head extension and mouth opening impair the ability to swallow in the supine
      position.
AB  - Head position and mouth opening in the supine position may impair the ability to
      swallow. If this does occur, it would lead to retention of intra-oral fluids
      during dental treatment, which would lead to stimulation of the cough reflex.
      This study was conducted to investigate how head position and mouth opening
      affect swallowing ability. The water swallowing test was performed in 13 healthy
      adult subjects in the supine position. The subjects were asked to swallow 10 mL
      of water that was injected into the mouth in a single attempt. After swallowing,
      the residual intra-oral water was suctioned and its volume was measured. An
      electromyogram (EMG) of the suprahyoid (SH) muscles was also recorded during the
      test. The duration of SH muscle activity and peak amplitude of SH EMG were
      examined. The water swallowing test was performed under three head positions
      (neutral, extended and flexed) and four mouth opening patterns (interincisal
      distances of 0, 20, 30 and 40 mm). The wider the subject opened the mouth, the
      more the water remained in the mouth after swallowing. The residual volume of
      water was more in the extended position compared with that in the neutral and
      flexed positions. Peak amplitude of SH EMG decreased with mouth opening. Duration
      of SH muscle activity was longer in the extended position than in the neutral and
      flexed positions. Head extension and mouth opening can induce difficulty in
      swallowing in the supine position by extending the duration of SH muscle activity
      while reducing its intensity.

PMID- 24738928
TI  - Re-evaluation of the 2,2-diphenyl-1-picrylhydrazyl free radical (DPPH) assay for
      antioxidant activity.
AB  - Kinetics and stoichiometry of reactions between the 2,2-diphenyl-1-picrylhydrazyl
      (DPPH) stable radical and 25 antioxidant compounds with different structure,
      molecular weight, number of -OH groups, and redox potential were investigated by
      recording the loss of DPPH(*) absorbance at 515 nm continuously for 10 min. A
      series of antioxidant concentrations was tested to determine linear response
      ranges and reaction saturation points. The primary feature distinguishing
      antioxidant activity--rate of initial reaction (<30 s)--was controlled by whether
      the dominant antioxidant mechanism was electron (very fast) or hydrogen atom
      (slow) transfer and by impairment of steric accessibility to the DPPH radical
      site by bulky ring adducts and multiple phenolic rings. Results raise serious
      questions regarding application of the DPPH assay for ranking antioxidants and
      natural extracts and suggest possible redirection of this assay to distinguish
      active reaction mechanisms by comparing reactions rates and patterns in different
      solvents and in 50% water/methanol mixtures at different pH values.

PMID- 24738929
TI  - Simultaneous enrichment and optical detection of low levels of stressed
      Escherichia coli O157:H7 in food matrices.
AB  - AIMS: Rapid detection of enterohaemorrhagic E. coli O157:H7 in large range of
      stress conditions occurring in food processing. METHODS AND RESULTS: Detection of
      E. coli O157:H7 in various food processing stress conditions using surface
      plasmon resonance imaging (SPRi) technique on an antibody microarray was
      evaluated. The direct detection method based on the culture/capture/measure (CCM)
      process consists of detecting bacteria during an enrichment step, which
      significantly decreases the overall assay duration. In optimized culture
      conditions, this method allows the specific detection of low CFU ml(-1) in <7 h.
      Detection of bacteria directly in contaminated food samples was also conducted.
      CONCLUSIONS: The CCM technique using an antibody microarray is a label-free
      immunoassay that allows rapid detection of E. coli O157:H7 in both food
      processing stress conditions and complex food matrices. SIGNIFICANCE AND IMPACT
      OF THE STUDY: The assay is promising for detecting E. coli O157:H7 at different
      steps of food and drink processing and during storage. SPRi appears to be a
      suitable and powerful detection method for routine quality controls in food
      industry with important economic and societal impact.

PMID- 24738930
TI  - Probing differential hydration of poly(vinylpyrrolidone) thin films using tracer
      mobility: an insight from fluorescence correlation spectroscopy.
AB  - Dynamics of small probe molecules have been routinely used to unravel the
      intrinsic details of charged ion transport in polymer brushes and polyelectrolyte
      multilayer (PEM) thin films. However, corresponding morphological properties
      affected with absorption of moisture have been hardly dealt with despite numerous
      applications of isotropic thin films in material chemistry and medical purposes.
      We have explored the overall structural changes associated with plasticization of
      PVP thin films by probing dynamics of small reporter (rhodamine 6G, Rh6G)
      molecules using fluorescence correlation spectroscopy (FCS). It was observed that
      under lesser amounts of absorbed moisture, the rigidity of the film matrix was
      high enough to inhibit appreciable molecular mobility. Nonetheless, with gradual
      increase in the moisture level within the film, molecular movement became
      extremely facile, so much so that it almost attained close to a solution like
      state. Molecular mobility was found to be dependent on both the method of
      preparation and the thickness of the thin films. The diffusivities mostly
      followed anomalous subdiffusive behaviors, reminiscent of dynamics of tracers in
      crowded cellular environments. The mobility was found to be independent of any
      electrostatic interaction between probe and polymer thin film. Hence, the tracer
      dynamics was attributed most likely to the viscoelasticity of the thin film
      matrix. 

PMID- 24738931
TI  - Reversible cysteine oxidation in hydrogen peroxide sensing and signal
      transduction.
AB  - Activation of redox cascades through hydrogen peroxide-mediated reversible
      cysteine oxidation is a major mechanism for intracellular signaling.
      Understanding why some cysteine residues are specifically oxidized, in
      competition with other proximal cysteine residues and in the presence of strong
      redox buffers, is therefore crucial for understanding redox signaling. In this
      review, we explore the recent advances in thiol-redox chemistry linked to
      signaling. We describe the last findings in the field of redox sensors, those
      that are naturally present in different model organisms as well as those that
      have been engineered to quantify intracellular hydrogen peroxide concentrations.
      Finally, we provide a summary of the newest approaches developed to study
      reversible cysteine oxidation at the proteomic level.

PMID- 24738932
TI  - Morphology change and detachment of lipid bilayers from the mica substrate driven
      by graphene oxide sheets.
AB  - Understanding the interaction between graphene oxide (GO) and a lipid membrane is
      significant for exploring the biocompatibility and cytotoxicity of GO, which is
      the basis for utilizing GO in the fields of biosensors, bioimaging, drug
      delivery, antibacterials, and so on. In this article, we monitored the dynamic
      process of the morphology change and detachment of lipid bilayers on mica
      substrates prompted by GO sheets by in situ atomic force microscope (AFM)
      imaging. It was found that the bare lipid bilayer dramatically expanded in height
      and would be unstable and detachable from the mica substrates as induced by GO.
      The detached lipid molecules were found to bind to the GO surface. The results
      also imply that GO is likely to influence the height and stability of the
      supported lipid bilayers (SLBs) by adsorbing metal ions such as calcium ions that
      were used to stabilize the bilayer structures on the mica substrate. These
      findings illustrate a complicated effect of GO on the SLBs and should be helpful
      in future applications of GO in biotechnology. 

PMID- 24738933
TI  - The effect of vitamin B1 on bleeding and spotting in women using an intrauterine
      device: a double-blind randomised controlled trial.
AB  - OBJECTIVES: Excessive menstrual bleeding, the most common complication caused by
      intrauterine devices (IUDs), often leads to discontinuation of use. Our study
      investigates the effect of vitamin B1 on menstrual bleeding and spotting after
      insertion of the TCu380A IUD. METHODS: This double-blind, randomised controlled
      trial involved 110 Iranian women. We recruited women who noted that their
      menstrual flow (duration, amount, and number of sanitary pads needed) or
      intermenstrual spotting had increased one month after the insertion of a TCu380A,
      and randomly assigned them to two groups. The intervention group and the control
      group received 100 mg of vitamin B1 or a placebo, respectively, daily, for three
      months. We followed all participants for four months. The Higham scale was used
      for estimating the volume of menstrual bleeding. The Mann-Whitney test, paired t
      test, independent t-test and Repeated Measure test were used for statistical
      purposes. RESULTS: In the intervention group the duration of menstrual bleeding,
      the number of sanitary pads and the amount of spotting decreased significantly
      compared to the control group (p < 0.001). CONCLUSION: Vitamin B1 is a safe,
      natural and cost-effective supplement that is devoid of side effects and reduces
      menstrual bleeding and spotting caused by a copper bearing-IUD.

PMID- 24738934
TI  - Systemic disease sequelae in chronic inflammatory diseases and chronic
      psychological stress: comparison and pathophysiological model.
AB  - In chronic inflammatory diseases (CIDs), the neuroendocrine-immune crosstalk is
      important to allocate energy-rich substrates to the activated immune system.
      Since the immune system can request energy-rich substrates independent of the
      rest of the body, I refer to it as the "selfish immune system," an expression
      that was taken from the theory of the "selfish brain," giving the brain a similar
      position. In CIDs, the theory predicts the appearance of long-term disease
      sequelae, such as metabolic syndrome. Since long-standing energy requirements of
      the immune system determine disease sequelae, the question arose as to whether
      chronic psychological stress due to chronic activation of the brain causes
      similar sequelae. Indeed, there are many similarities; however, there are also
      differences. A major difference is the behavior of body weight (constant in CIDs
      versus loss or gain in stress). To explain this discrepancy, a new
      pathophysiological theory is presented that places inflammation and stress axes
      in the middle. 

PMID- 24738935
TI  - A femtomolar level and highly selective 17beta-estradiol photoelectrochemical
      aptasensor applied in environmental water samples analysis.
AB  - Driven by the urgent demand of determining low level of 17beta-estradiol (E2)
      present in environment, a novel and ultrasensitive photoelectrochemical (PEC)
      sensing platform based on anti-E2 aptamer as the biorecognition element was
      developed onto CdSe nanoparticles-modified TiO2 nanotube arrays. The designed PEC
      aptasensor exhibits excellent performances in determination of E2 with a wide
      linear range of 0.05-15 pM. The detection limit of 33 fM is lower than the
      previous reports. The aptasensor manifests outstanding selectivity to E2 while
      used to detect seven other endocrine disrupting compounds that have similar
      structure or coexist with E2. The superior sensing behavior toward E2 can be
      attributed to the appropriate PEC sensing interface resulting from the
      preponderant tubular microstructure and excellent photoelectrical activity, the
      large packing density of aptamer on the sensing interface, as well as the high
      affinity of the aptamer to E2. The PEC aptasensor was applied successfully to
      determine E2 in environmental water samples without complicate sample
      pretreatments, and the analytical results showed good agreement with that
      determined by HPLC. Thus, a simple and rapid PEC technique for detection low
      level of E2 was established, having promising potential in monitoring
      environmental water pollution. 

PMID- 24738936
TI  - Surface characterization and osteoblast response to a functionally graded
      hydroxyapatite/fluoro-hydroxyapatite/titanium oxide coating on titanium surface
      by sol-gel method.
AB  - OBJECTIVES: To improve efficacy of current titanium and its alloys, in
      bioactivity and speed of osseointegration, of orthopaedic implants. MATERIALS AND
      METHODS: A novel triple-layered functional graded coating, consisting of a porous
      hydroxyapatite (HA) outermost layer, fluoro-HA (FHA) intermediate layer and
      titanium oxide (TiO2 ) innermost layer, was created on a titanium substrate by a
      multistep sol-gel method. X-ray diffraction analysis showed TiO2 anatase and
      apatite crystallization in the coating. RESULTS: Morphological analysis performed
      by scanning electron microscopy showed excellent bonding between coating and
      substrate, with a thickness of ~2 MUm. Scratch testing found favourable adhesion
      strength of the composite coating. In addition, optical microscope images
      suggested good biocompatibility. Considering thet in vitro cell response,
      osteoblasts on the coating exhibited higher cell proliferation and ALP activity
      compared to pure titanium and HA coating, and demonstrated excellent coating
      bioactivity. CONCLUSIONS: Current results indicated that the novel TiO2 /FHA/HA
      coating has promising clinical applications in orthopaedic and dental
      implantation.

PMID- 24738937
TI  - Expression profiling reveals functionally redundant multiple-copy genes related
      to zinc, iron and cadmium responses in Brassica rapa.
AB  - Genes underlying environmental adaptability tend to be over-retained in polyploid
      plant species. Zinc deficiency (ZnD) and iron deficiency (FeD), excess Zn (ZnE)
      and cadmium exposure (CdE) are major environmental problems for crop cultivation,
      but little is known about the differential expression of duplicated genes upon
      these stress conditions. Applying Tag-Seq technology to leaves of Brassica rapa
      grown under FeD, ZnD, ZnE or CdE conditions, with normal conditions as a control,
      we examined global gene expression changes and compared the expression patterns
      of multiple paralogs. We identified 812, 543, 331 and 447 differentially
      expressed genes under FeD, ZnD, ZnE and CdE conditions, respectively, in B. rapa
      leaves. Genes involved in regulatory networks centered on the transcription
      factors bHLH038 or bHLH100 were differentially expressed under (ZnE-induced) FeD.
      Further analysis revealed that genes associated with Zn, Fe and Cd responses
      tended to be over-retained in the B. rapa genome. Most of these multiple-copy
      genes showed the same direction of expression change under stress conditions. We
      conclude that the duplicated genes involved in trace element responses in B. rapa
      are functionally redundant, making the regulatory network more complex in B. rapa
      than in Arabidopsis thaliana. 

PMID- 24738938
TI  - Finger Tapping Test performance as a measure of performance validity.
AB  - The Finger Tapping Test (FTT) has been presented as an embedded measure of
      performance validity in most standard neuropsychological evaluations. The present
      study evaluated the utility of three different scoring systems intended to detect
      invalid performance based on FTT. The scoring systems were evaluated in
      neuropsychology cases from clinical and independent practices, in which credible
      performance was determined based on passing all performance validity measures or
      failing two or more validity indices. Each FTT scoring method presented with
      specificity rates at approximately 90% and sensitivity of slightly more than 40%.
      When suboptimal performance was based on the failure of any of the three scoring
      methods, specificity was unchanged and sensitivity improved to 50%. The results
      are discussed in terms of the utility of combining multiple scoring measures for
      the same test as well as benefits of embedded measures administered over the
      duration of the evaluation. 

PMID- 24738939
TI  - Absorption, distribution, metabolism and excretion of gemigliptin, a novel
      dipeptidyl peptidase IV inhibitor, in rats.
AB  - 1. The absorption, distribution, metabolism and excretion of a novel dipeptidyl
      peptidase IV inhibitor, gemigliptin, were examined following single oral
      administration of (14)C-labeled gemigliptin to rats. 2. The (14)C-labeled
      gemigliptin was rapidly absorbed after oral administration, and its
      bioavailability was 95.2% (by total radioactivity). Distribution to specific
      tissues other than the digestive organs was not observed. Within 7 days after
      oral administration, 43.6% of the administered dose was excreted via urine and
      41.2% was excreted via feces. Biliary excretion of the radioactivity was about
      17.7% for the first 24 h. After oral administration of gemigliptin to rats, the
      in vivo metabolism of gemigliptin was investigated with bile, urine, feces,
      plasma and liver samples. 3. The major metabolic pathway was hydroxylation, and
      the major circulating metabolites were a dehydrated metabolite (LC15-0516) and
      hydroxylated metabolites (LC15-0635 and LC15-0636).

PMID- 24738940
TI  - Novel method of tetramic acid synthesis: silver-catalyzed carbon dioxide
      incorporation into propargylic amine and intramolecular rearrangement.
AB  - Tetramic acid derivatives have been studied as biologically active heterocycle
      structures for pharmaceutical or agricultural chemicals. Conventional preparative
      approaches often require highly functionalized starting materials and harsh
      heating conditions in basic media. The present report provides a conceptually new
      synthetic strategy for the synthesis of tetramic acid derivatives from easily
      available propargylic amines and carbon dioxide with a silver salt and DBU under
      mild reaction conditions. 

PMID- 24738941
TI  - Lymphoma associated hemophagocytic syndrome: it's going viral.

PMID- 24738943
TI  - Abstracts from the Annual Scientific Meeting of the BSGI, 24-25 April 2014,
      London, England.

PMID- 24738942
TI  - Post-chemotherapy cognitive impairment in patients with B-cell non-Hodgkin
      lymphoma: a first comprehensive approach to determine cognitive impairments after
      treatment with rituximab, cyclophosphamide, doxorubicin, vincristine and
      prednisone or rituximab and bendamustine.
AB  - To assess the effects of chemoimmunotherapy on post-chemotherapy cognitive
      impairments (PCCI) in patients with B-cell non-Hodgkin lymphoma (NHL), we used
      objective and subjective measures of cognitive functions in combination with
      serum parameters and neuroelectric recordings. Self-perceived status of
      cognition, fatigue and emotional functioning were reduced in patients (n=30)
      compared to healthy controls (n=10). Cognitive performance was impaired in
      patients with NHL compared to controls and a norm sample (n=1179). PCCI was more
      severe in patients treated with rituximab and bendamustine (BR) than in patients
      who received R in combination with CHOP (cyclophosphamide, doxorubicin,
      vincristine, prednisone) polychemotherapy (R-CHOP). Individual alpha peak
      frequency and serum brain-derived neurotrophic factor (BDNF) levels in patients
      with NHL correlated with accuracy in the objective cognition test. Higher serum
      interleukin-6 (IL-6) concentrations were associated with higher fatigue levels.
      Patients with NHL and especially those who were treated with BR were affected by
      PCCI. BDNF and IL-6 might be involved in the pathogenesis of PCCI and fatigue.

PMID- 24738944
TI  - A scoping review of published research on the relinquishment of companion
      animals.
AB  - Globally, large populations of companion animals are relinquished each year. The
      purpose of this scoping review was to identify all published research
      investigating companion-animal relinquishment to map out and evaluate research
      gaps, needs, and opportunities. A comprehensive search strategy was implemented
      in 4 online databases, identified citations were screened, and relevant articles
      were procured and characterized. From 6,848 unique citations identified, 192 were
      confirmed relevant, including 115 primary-research articles and 77 reviews and
      commentaries. The majority of these articles originated from the United States
      (131; 68.2%); 74 (38.5%) of them have been published since 2006. Among the
      primary-research articles, 84 (73.0%) investigated reasons for companion-animal
      relinquishment. The most commonly studied reasons were aggressive companion
      animal behaviors (49; 58.3%); moving, rental, or housing issues (45; 53.6%); and
      caretaker personal issues (42; 50.0%). Only 17 primary-research articles
      investigated interventions to prevent companion-animal relinquishment. The
      quantity of research into reasons for relinquishment highlights an opportunity
      for future knowledge-synthesis activities in this area, including systematic
      review and meta-analysis. In comparison, the limited research into interventions
      identifies a priority for new research. 

PMID- 24738945
TI  - Periorbital edema.

PMID- 24738947
TI  - Understanding the biology of reactive oxygen species and their link to cancer:
      NADPH oxidases as novel pharmacological targets.
AB  - Reactive oxygen species (ROS), the cellular products of myriad physiological
      processes, have long been understood to lead to cellular damage if produced in
      excess and to be a causative factor in cancer through the oxidation and nitration
      of various macromolecules. Reactive oxygen species influence various hallmarks of
      cancer, such as cellular proliferation and angiogenesis, through the promotion of
      cell signalling pathways intrinsic to these processes and can also regulate the
      function of key immune cells, such as macrophages and regulatory T cells, which
      promote angiogenesis in the tumour environment. Herein we emphasize the family of
      NADPH oxidase enzymes as the most likely source of ROS, which promote
      angiogenesis and tumourigenesis through signalling pathways within endothelial,
      immune and tumour cells. In this review we focus on the pharmacological
      inhibitors of NADPH oxidases and suggest that, compared with traditional anti
      oxidants, they are likely to offer better alternatives for suppression of tumour
      angiogenesis. Despite the emerging enthusiasm towards the use of NADPH oxidase
      inhibitors for cancer therapy, this field is still in its infancy; in particular,
      there is a glaring lack of knowledge of the roles of NADPH oxidases in in vivo
      animal models and in human cancers. Certainly a clearer understanding of the
      relevant signalling pathways influenced by NADPH oxidases during angiogenesis in
      cancer is likely to yield novel therapeutic approaches. 

PMID- 24738946
TI  - Inositol phosphate recycling regulates glycolytic and lipid metabolism that
      drives cancer aggressiveness.
AB  - Cancer cells possess fundamentally altered metabolism that supports their
      pathogenic features, which includes a heightened reliance on aerobic glycolysis
      to provide precursors for synthesis of biomass. We show here that inositol
      polyphosphate phosphatase 1 (INPP1) is highly expressed in aggressive human
      cancer cells and primary high-grade human tumors. Inactivation of INPP1 leads to
      a reduction in glycolytic intermediates that feed into the synthesis of the
      oncogenic signaling lipid lysophosphatidic acid (LPA), which in turn impairs LPA
      signaling and further attenuates glycolytic metabolism in a feed-forward
      mechanism to impair cancer cell motility, invasiveness, and tumorigenicity. Taken
      together these findings reveal a novel mode of glycolytic control in cancer cells
      that can serve to promote key oncogenic lipid signaling pathways that drive
      cancer pathogenicity.

PMID- 24738948
TI  - Adjustable augmented rectus muscle transposition surgery with or without ciliary
      vessel sparing for abduction deficiencies.
AB  - BACKGROUND: Vertical rectus transposition (VRT) is useful in abduction
      deficiencies. Posterior fixation sutures enhance the effect of VRT, but usually
      preclude the use of adjustable sutures. Augmentation of VRT by resection of the
      transposed muscles allows for an adjustable technique that can reduce induced
      vertical deviations and overcorrections. METHODS: We retrospectively reviewed the
      records of all patients undergoing adjustable partial or full tendon VRT
      augmented by resection of the transposed muscles. Ciliary vessels were preserved
      in most of the patients by either splitting the transposed muscle or by dragging
      the transposed muscle without disrupting the muscle insertion. RESULTS: Seven
      patients with abducens palsy and one with esotropic Duane syndrome were included.
      Both vertical rectus muscles were symmetrically resected by 3-5 mm. Preoperative
      central gaze esotropia of 30.6 +/- 12.9Delta (range, 17-50Delta) decreased to
      10.6 +/- 8.8Delta (range, 0-25Delta) at the final visit (p = 0.003). Three
      patients required postoperative adjustment by recession of one of the transposed
      muscles due to an induced vertical deviation (mean 9.3Delta reduced to 0Delta),
      coupled with overcorrection (mean exotropia 11.3Delta reduced to 0 in two
      patients and exophoria 2Delta in one patient). At the final follow-up visit 3.8
      +/- 2.6 months postoperatively, one patient had a vertical deviation <4Delta, and
      none had overcorrection or anterior segment ischemia. Three patients required
      further surgery for recurrent esotropia. CONCLUSIONS: Augmentation of VRT by
      resection of the transposed muscles can be performed with adjustable sutures and
      vessel-sparing technique. This allows for postoperative control of
      overcorrections and induced vertical deviations as well as less risk of anterior
      segment ischemia.

PMID- 24738949
TI  - Comparing the SureSight autorefractor and the plusoptiX photoscreener for
      pediatric vision screening.
AB  - PURPOSE: Both the plusoptiX photoscreener photoscreener and the SureSight
      autorefractor can be used to objectively screen for amblyogenic risk factors in
      children. We compare the plusoptiX and the SureSight to a pediatric ophthalmology
      examination on a single cohort of children. METHODS: We performed a retrospective
      medical records review of 90 children. Each patient was screened with both the
      PlusoptiX A09 and SureSight devices on the same day as part of a comprehensive
      pediatric ophthalmic examination. The ages of the patients ranged from <1 to 17
      years. All patients had a cycloplegic refraction on the day of their exam, or
      within the previous 6 months. RESULTS: Of the children reviewed, 71% had
      amblyopia risk factors. The plusoptiX demonstrated a sensitivity of 98% and a
      specificity of 88%. The SureSight demonstrated a sensitivity of 95% and a
      specificity of 65% utilizing the manufacturer's criteria. CONCLUSION: The
      SureSight and plusoptiX were both found to be reliable objective vision screening
      devices, though the plusoptiX did have a higher sensitivity and specificity than
      the SureSight using the manufacturer's referral criteria. Using the Vision In
      Preschoolers Study (VIPS) referral criteria, the specificity of the SureSight
      improved but the sensitivity was reduced.

PMID- 24738950
TI  - Reply to letter to the editor: Expert opinion on best practice guidelines and
      competency framework for visual screening in children.

PMID- 24738951
TI  - The effects of mild-to-severe retinopathy of prematurity on the development of
      refractive errors and strabismus.
AB  - PURPOSE: To investigate the effects of mild-to-severe retinopathy of prematurity
      (ROP) on refractive state and the incidence of strabismus. MATERIALS AND METHODS:
      Infants born <=32 weeks of gestation were prospectively evaluated. Inclusion
      criteria were a follow-up of at least 6 months and at least stage 1 ROP. Group 1
      included stage 1 ROP cases. Cases with stage 2 or 3 ROP without indication for
      treatment formed the second group. Group 3 included cases who received treatment
      for ROP. Logistic regression, adjusted for birth weight and gestational age, and
      multiple comparison tests were used to compare outcomes among groups. RESULTS:
      The mean follow-up time was 20.9 +/- 6.6 months. In the first (n = 21), second (n
      = 22), and third groups (n = 23), the right spherical equivalents (SE) were 1.17
      +/- 1.33, -0.18 +/- 3.09, and -1.08 +/- 4.05 diopters, and the left SEs were 1.23
      +/- 1.34, -0.09 +/- 3.24, and -1.46 +/- 4.02 diopters, respectively (p = 0.026
      for right SE and 0.008 for left SE). The incidences of anisometropia were 3/21,
      4/22, and 11/23 in the first, second, and third groups, respectively (adjusted
      odds ratios [aOR] for group 3 vs 1 = 5.39, aOR for group 3 vs 2 = 4.06).
      Strabismus developed in 7/21, 6/22, and 10/23 in groups one, two, and three,
      respectively (aOR for group 3 vs 1 = 2.06, aOR for group 3 vs 2 = 2.27). Eighteen
      of these were esotropias. CONCLUSIONS: Refractive errors and strabismus were
      associated with mild-to-severe ROP. Esotropia was the most frequent type of
      strabismus.

PMID- 24738952
TI  - Clinical features and surgical outcomes of isolated inferior rectus muscle
      paralysis.
AB  - PURPOSE: To describe clinical features of patients with unilateral isolated
      inferior rectus (IR) muscle paralysis along with type of surgical treatment and
      results after surgery. METHODS: Patients diagnosed with unilateral isolated IR
      muscle palsy between 2009 and 2012 that required surgical treatment were included
      in the study. Diagnosis of IR muscle palsy was done by hypertropia with the
      largest angle in depression and abduction and inferior rectus muscle underaction.
      RESULTS: Twenty-two patients remained in the study; 17 patients (77.3%) had left
      eye involvement. IR muscle paresis was traumatic in 12 patients (54.5%),
      congenital in 9 patients (40.9%), and vascular in 1 patient (4.5%). Limitation of
      duction in the gaze of IR muscle was -2 to -3 in all cases. 3 patients,
      paradoxically, had contralateral compensatory head tilt (compensatory head tilt
      to the opposite side of IR muscle palsy). Intraoperatively, we did not detect any
      gross abnormalities in the IR muscles. The surgical plan at the first operation
      was IR muscle resection alone in 13 patients (59.1%). At the last follow-up
      visit, 15 patients (68%) had no deviations in primary position and downgaze.
      Three cases needed reoperation. CONCLUSION: The presence of both ipsilateral and
      contralateral compensatory head postures in our patients showed that three-step
      or head-tilt test is not helpful in the diagnosis of IR muscle palsy. In
      comparison with other studies, more patients in our study were treated with IR
      muscle resection alone. Also, our reoperation rate was lower than other studies.
      Absence of gross abnormality in the IR muscles at the operation and partial
      nature of the paresis may explain these good results. Thus, a considerable number
      of IR muscle palsy cases with the above characteristics may be treated
      successfully by one muscle surgery (IR muscle resection).

PMID- 24738953
TI  - Beliefs in moral luck: When and why blame hinges on luck.
AB  - Belief in moral luck is represented in judgements that offenders should be held
      accountable for intent to cause harm as well as whether or not harm occurred.
      Scores on a measure of moral luck beliefs predicted judgements of offenders who
      varied in intent and the outcomes of their actions, although judgements overall
      were not consistent with abstract beliefs in moral luck. Prompting participants
      to consider alternative outcomes, particularly worse outcomes, reduced moral luck
      beliefs. Findings suggest that some people believe that offenders should be
      punished based on the outcome of their actions. Furthermore, prompting
      counterfactuals decreased judgements consistent with moral luck beliefs. The
      results have implications for theories of moral judgement as well as legal
      decision making.

PMID- 24738954
TI  - Impact of two ant species on egg parasitoids released as part of a biological
      control program.
AB  - Biological control using Trichogramma pretiosum Riley (Hymenoptera:
      Trichogrammatidae), an egg parasitoid wasp, was tested in Uruguay to reduce
      populations of lepidopteran pests on soybeans. It was observed that the
      commercial parasitoid dispensers, which were made of cardboard, were vulnerable
      to small predators that succeeded in entering and emptying the containers of all
      the eggs parasitized by T. pretiosum. Observations in a soybean crop showed that
      the only small, common predators present were two ant species. The species
      responsible for the above mentioned predation was determined from the results of
      a laboratory experiment in which the behavior of the two common ants was tested.
      A modification of the dispensers to prevent introduction of this ant has been
      proposed and successfully tested in the laboratory and in the field.

PMID- 24738956
TI  - Destabilization of i-motif by submolar concentrations of a monovalent cation.
AB  - Counterions are crucial for self-assembly of nucleic acids. Submolar monovalent
      cations are generally deemed to stabilize various types of base pairs in nucleic
      acids such as Watson-Crick and Hoogsteen base pairs via screening of
      electrostatic repulsion. Besides monovalent cations, acidic pH is required for i
      motif formation because protons facilitate pairing between cytosines. Here we
      report that Li(+) ions destabilize i-motif, whereas other monovalent cations,
      Na(+) and K(+), have the usual stabilizing effect. The thermodynamics data alone,
      however, cannot reveal which mechanism, enhanced unfolding or suppressed folding
      or both, is responsible for the Li(+)-induced destabilization. To gain further
      insight, we examined the kinetics of i-motif. To deal with slow kinetics of i
      motif, we developed a method dubbed HaRP to construct a long FRET time trace to
      observe a sufficient number of transitions. Our kinetics analysis shows clearly
      that Li(+) ions promote unfolding of i-motif but do not hinder its folding,
      lending strong support for our hypothesis on the origin of this unusual effect of
      Li(+). Although the subangstrom size of Li(+) ions allows them to infiltrate the
      space between cytosines in competition with protons, they cannot adequately
      fulfill the role of protons in mediating the hydrogen bonding of cytosine pairs. 

PMID- 24738957
TI  - 3-Bromopyruvic acid, a hexokinase II inhibitor, is an effective antitumor agent
      on the hepatoma cells : in vitro and in vivo findings.
AB  - Over-expressed in cancer cells, hexokinase II (HK II) forms a mitochondrial
      complex, which promotes cancer survival. 3- Bromopyruvic acid (3-BrPA)
      dissociates HK II from this complex, causing cell death, and thus, having an anti
      tumor effect. The design of this study was to first analyze the expression of HK
      II in the hepatoma cell line, BEL-7402, then investigate the effects of 3-Br-PA
      on these cells, and finally, discuss its potential for clinical usage. HK II
      expression was detected in BEL-7402 cells by immunocytochemistry and reverse
      transcriptase polymerase chain reaction (RT-PCR). In vitro treatment of cells
      with 3-BrPA significantly inhibited their growth, as evaluated by MTT assay and
      adenosine triphosphate-tumor chemosensitivity assay (ATP-TCA). To analyze the in
      vivo function and safety of this drug, a tumor model was established by
      subcutaneously implanting hepatic cancer cells into nude mice. 3-BrPA treatment
      (50 mg/kg ip. daily, 6 days/week for three weeks) was effective in the animal
      model by attenuating tumor growth and causing tumor necrosis. Toxic signs were
      not observed. The acute toxicity study provided an LD50 of 191.7 mg/kg for 3
      BrPA. Taken together, our in vitro and in vivo analyses suggest that 3-BrPA
      exerts anti-hepatoma effects, and may be an effective pharmacological agent for
      the treatment of hepatocellular carcinoma. 

PMID- 24738958
TI  - Oral chemotherapy in elderly women with metastatic breast cancer.
AB  - Life expectancy has significantly increased over the past 30 years, with a
      greater prevalence of diverse disease states, especially cancer. As older persons
      are a very heterogeneous group with an increased prevalence of comorbidities and
      a relative inability to tolerate the adverse effects of chemotherapy, the
      treatment of cancer in the elderly is particularly demanding. The principles of
      its management are similar to those in younger patients but with special
      considerations linked to comorbidities and clinical status. The objective of
      chemotherapeutic treatment in metastatic breast cancer has historically been
      primarily palliative. The introduction of newer approaches with improved or at
      least equivalent efficacy and reduced toxicity is highly desirable. Such
      approaches may include the use of less toxic drugs, more convenient routes of
      administration (e.g., oral) and home-based (outpatient) rather than hospital
      based therapies. The available oral cytostatic drugs include vinorelbine and
      capecitabine. In this review, we analyze oral cytostatic drugs in the elderly
      patient diagnosed with metastatic breast cancer. 

PMID- 24738959
TI  - New drugs for follicular lymphoma in older adults.
AB  - Follicular lymphoma is essentially a disease of the elderly, and the aging of the
      population in developed countries will increase patient numbers in coming years.
      Significant achievements have been made for treatment, but better understanding
      of the disease and major progress in biology now facilitate the development of
      many new drugs, which may have improved toxicity profiles making them appropriate
      for treatment of older adults. However, the increasing number of treatment
      possibilities, can also increase the toxicity risks, and unexpected toxicities
      specific to older adults may be encountered. Consequently, specific studies of
      older patients should be considered, using appropriate evaluation tools such as
      comprehensive geriatric assessment. This review will described the development of
      these new drugs, in the context of the treatment of older-adults with follicular
      lymphoma. 

PMID- 24738960
TI  - Turn helical motifs from pair to single entangled double helixes in a cobalt
      vanadate system via introduction of a V-shaped ligand.
AB  - Two novel helical compounds based on polyoxovanadates, [Co(H2O)2V2O6] (1) and
      [Co(bimb)V2O6] (2) (bimb = 1,3-bis(1-imidazoly)benzene), have been synthesized
      under identical hydrothermal conditions, providing two structurally different
      helical motifs due to introduction of a V-shaped bimb ligand in 2. Compound 1
      possesses a pair of entanglement double helixes in a 3D inorganic framework,
      whereas compound 2 shows a single entangled double helix in a 3D inorganic
      organic network owing to the influences of steric hindrance of ligands as well as
      coordination geometries of metal cations. The electrocatalytic and photocatalytic
      properties of 1 and 2 were also investigated in details.

PMID- 24738961
TI  - Antagonistic effects between magnetite nanoparticles and a hydrophobic surfactant
      in highly concentrated Pickering emulsions.
AB  - Herein we present a systematic study of the antagonistic interaction between
      magnetite nanoparticles (Fe3O4) and nonionic hydrophobic surfactant in Pickering
      highly concentrated emulsions. Interfacial tension measurements, phase behavior,
      and emulsion stability studies, combined with electron microscopy observations in
      polymerized systems and magnetometry, are used to support the discussion. First,
      stable W/O highly concentrated emulsions were obtained using partially
      hydrophobized magnetite nanoparticles. These emulsions experienced phase
      separation when surfactant is added at concentrations as low as 0.05 wt %. Such
      phase separation arises from the preferential affinity of the surfactant for the
      nanoparticle surfaces, which remarkably enhances their hydrophobicity, leading to
      a gradual desorption of nanoparticles from the interface. W/O emulsions were
      obtained at higher surfactant concentrations, but in this case, these emulsions
      were mainly stabilized by surfactant molecules. Therefore, stable emulsions could
      be prepared in two separate ranges of surfactant concentrations. After
      polymerization, low-density macroporous polymers were obtained, and the
      adsorption and aggregation of nanoparticles was analyzed by transmission electron
      microscopy. The progressive displacement of the nanoparticles was revealed: from
      the oil-water interface, in which aggregated nanoparticles were adsorbed, forming
      dense layers, to the continuous phase of the emulsions, where small nanoparticle
      aggregates were randomly dispersed. Interestingly, the results also show that the
      blocking temperature of the iron oxide superparamagnetic nanoparticles embedded
      in the macroporous polymers could be modulated by appropriate control of the
      concentrations of both surfactant and nanoparticles. 

PMID- 24738962
TI  - Renal function preservation with the mTOR inhibitor, Everolimus, after lung
      transplant.
AB  - Chronic kidney disease (CKD) is a common complication of calcineurin inhibitors
      (CNIs) in solid organ transplantation. Previous data suggest that the use of
      everolimus as an immunosuppressant drug leads to improvement in renal function.
      The aim of our study was to establish the effect of everolimus in combination
      with lower doses of CNIs on renal function among lung transplant recipients. Data
      regarding renal function and pulmonary function were collected from 41 lung
      transplanted patients in whom treatment was converted to a combination of
      everolimus with lower doses of CNIs. Patients transferred to everolimus and low
      dose CNIs showed an improvement in renal function. Patients who continued
      treatment with everolimus showed improvement in renal function, as opposed to
      patients who discontinued the treatment. Subjects without proteinuria at baseline
      showed a better improvement compared with subjects with proteinuria. The
      incidence of graft rejection did not increase. We concluded that a protocol that
      includes everolimus and lower doses of CNIs is effective for preserving renal
      function in lung transplant recipients with CKD. We also believe that an early
      implementation of everolimus, before proteinuria occurs or creatinine clearance
      is reduced, could lead to better outcomes. 

PMID- 24738963
TI  - Hydration and conformational equilibrium in yeast thioredoxin 1: implication for
      H(+) exchange.
AB  - One of the ancestral features of thioredoxins is the presence of a water cavity.
      Here, we report that a largely hydrated, conserved, buried aspartic acid in the
      water cavity modulates the dynamics of the interacting loops of yeast thioredoxin
      1 (yTrx1). It is well-established that the aspartic acid, Asp24 for yTrx1, works
      as a proton acceptor in the reduction of the target protein. We propose a
      complementary role for Asp24 of coupling hydration and conformational motion of
      the water cavity and interacting loops. The intimate contact between the water
      cavity and the interacting loops means that motion at the water cavity will
      affect the interacting loops and vice versa. The D24N mutation alters the
      conformational equilibrium for both the oxidized and reduced states, quenching
      the conformational motion in the water cavity. By measuring the hydration and
      molecular dynamics simulation of wild-type yTrx1 and the D24N mutant, we showed
      that Asn24 is more exposed to water than Asp24 and the water cavity is smaller in
      the mutant, closing the inner part of the water cavity. We discuss how the
      conformational equilibrium contributes to the mechanism of catalysis and H(+)
      exchange. 

PMID- 24738964
TI  - Immunoregulatory mechanisms of vitamin D relevant to respiratory health and
      asthma.
AB  - Vitamin D deficiency is prevalent among people with various immune-mediated
      conditions, including autoimmune diseases and asthma. Serum 25(OH)D levels
      inversely correlate with asthma severity, glucocorticoid responsiveness/dosage,
      and markers of pathogenesis, such as airway remodeling, IgE, and eosinophilia.
      Trials involving supplementation with active vitamin D or a precursor are
      beginning to emerge with variable results that, in part, reflect differences in
      study design. This review looks at the mechanisms by which vitamin D may protect
      against asthma, including increasing glucocorticoid responsiveness, skewing
      immune cells towards a regulatory phenotype, reducing the incidence of
      infections, airway remodeling, eosinophilia, and lowering the levels of IgE. Also
      discussed is the therapeutic potential for vitamin D, which is likely to be
      applicable to immune-mediated conditions beyond simply asthma. 

PMID- 24738965
TI  - Sources of preanalytical error in pharmacokinetic analyses - focus on intravenous
      drug administration and collection of blood samples.
AB  - INTRODUCTION: Pharmacokinetic (PK) studies for long-established drugs are
      generally performed outside the well-standardized settings of pharmaceutical
      industry trials. Instead, such studies are usually performed within daily
      clinical practice of hospitals. AREAS COVERED: This article describes aspects of
      intravenous (i.v.) drug administration and blood sampling that contribute to
      potential sources of preanalytical errors for PK investigations. Parameters that
      bias determination of start and end time of i.v. infusions, as well as consistent
      rate of drug delivery, are discussed. Causes for drug loss in the infusion
      device, including adsorption and insufficient flushing, are outlined. The
      advantages and disadvantages of different blood sampling techniques are reviewed,
      with an emphasis on pediatric studies. EXPERT OPINION: For PK studies that are
      integrated into the general hospital routine, a variety of potential sources of
      error exist. Potential pitfalls depend on the specific drug and trial
      characteristics and they must be anticipated and discussed in advance. Working
      procedures need to be developed that address the anticipated problems and in
      detail describe procedures that need compliance between bed and bench.

PMID- 24738966
TI  - Microbial community structure of wastewater treatment subjected to high mortality
      rate due to ozonation of return activated sludge.
AB  - AIMS: This study investigated the effects of return activated sludge (RAS)
      ozonation, on the bacterial community structure of pilot-scale wastewater
      treatment systems. METHODS AND RESULTS: Two parallel activated sludge reactors
      were operated to treat real municipal wastewater for 98 days. The RAS of one of
      the reactors was subjected to increasing doses of ozone during the experimental
      period, which resulted in higher reduction in biosolids waste production and
      higher bacterial growth rate. The bacterial community structures were
      investigated by 16S rRNA gene amplicon high-throughput pyrosequencing and
      fluorescence in situ hybridization (FISH). The structures remained highly similar
      throughout the experiment despite the ozone treatment. Comparative analyses
      between pyrosequencing and FISH revealed clear discrepancies in the proportion of
      some bacterial populations. CONCLUSIONS: The results suggest that RAS ozonation
      is not a main environmental factor structuring the community composition.
      Instead, the parallel drifts and slight convergence of the two community
      structures indicate that other environmental factors such as influent wastewater
      composition and temperature may be more important. Care should be exercised in
      interpreting the proportion of sequence reads as pyrosequencing may be biased as
      compared to FISH. SIGNIFICANCE AND IMPACT OF THE STUDY: This study provides new
      insights on the importance of indiscriminate high mortality rates brought by
      external factors (here ozonation) on microbial community structures of activated
      sludge system.

PMID- 24738967
TI  - Delayed vasodilation is associated with cardiovascular risk.
AB  - BACKGROUND: Flow-mediated dilation (FMD) of the brachial artery is widely used to
      assess cardiovascular risk. In recent years, much attention has been paid to the
      kinetics of vasodilation in an attempt to better characterize the endothelial
      function. Here, we investigated whether FMD magnitude and/or latency are most
      related to individual cardiovascular risk. MATERIALS AND METHODS: Four hundred
      subjects were recruited. Individual risk prediction was estimated by Framingham
      cardiovascular risk score and CUORE project calculator. Subjects were divided
      into Early dilators (peak FMD at 50 s), Late dilators (peak FMD over 50 s) and No
      dilators. RESULTS: Cardiovascular risk was highest in No dilators and
      significantly higher in Late than Early dilators despite comparable peak FMD.
      When divided according to peak FMD quintiles, Early and Late dilators showed
      decreased cardiovascular risk with increasing magnitude of vasodilation. However,
      subjects in the first three quintiles of Late dilators had a markedly higher risk
      score despite a peak vasodilation similar to that of Early dilators. CONCLUSION:
      These results suggest that the magnitude of the FMD and its latency are both
      important for identifying patients at risk of cardiovascular disease. Subjects
      with a delayed though significant vasodilation associated with a blunted early
      response exhibit the highest cardiovascular risk.

PMID- 24738968
TI  - Parahydrogen induced polarization of 1-(13)C-phospholactate-d(2) for biomedical
      imaging with >30,000,000-fold NMR signal enhancement in water.
AB  - The synthetic protocol for preparation of 1-(13)C-phosphoenolpyruvate-d2,
      precursor for parahydrogen-induced polarization (PHIP) of 1-(13)C-phospholactate
      d2, is reported. (13)C nuclear spin polarization of 1-(13)C-phospholactate-d2 was
      increased by >30,000,000-fold (5.75 mT) in water. The reported (13)C polarization
      level approaching unity (>15.6%), long lifetime of (13)C hyperpolarized 1-(13)C
      phospholactate-d2 (58 +/- 4 s versus 36 +/- 2 s for nondeuterated form at 47.5
      mT), and large production quantities (52 MUmoles in 3 mL) in aqueous medium make
      this compound useful as a potential contrast agent for the molecular imaging of
      metabolism and other applications. 

PMID- 24738969
TI  - Positive correlation between the efficiency of induced pluripotent stem cells and
      the development rate of nuclear transfer embryos when the same porcine embryonic
      fibroblast lines are used as donor cells.
AB  - Induced pluripotent stem cells (iPSCs) and nuclear transfer (NT) are two of the
      primary routes to reprogram differentiated cells back to the pluripotent state.
      However, it is still unknown whether there is any correlation between the
      reprogramming efficiency of iPSCs and NT if the same donor cells are employed. In
      this study, six porcine embryonic fibroblast (PEF) lines from Landrace (L1, L6,
      L9) or Congjiang local pigs (C4, C5, C6) were used for iPSC induction and NT.
      Furthermore, the resultant iPSCs from four PEF lines (L1, L6, C4, and C5) were
      used for NT (iPSC-NT), and the expression of exogenous genes was detected in iPSC
      NT embryos by real-time PCR. The results showed that the efficiency of iPSC lines
      established from different PEF lines were significantly different. When the same
      PEF lines were used as donor cells for NT, the blastocysts rates were also
      different among different PEF lines and positively related with iPSCs induction
      efficiency. When the iPSCs were used as donor cells for NT, compared with the
      source PEFs, the blastocysts rates were significantly decreased. Real-time PCR
      results indicated that exogenous genes (Oct4, c-Myc) continued to be expressed in
      iPSC-NT embryos. In summary, our results demonstrate that there was a positive
      correlation between iPSCs and NT reprogramming efficiency, although the mechanism
      of these two routes is different. This may provide a new method to select the
      appropriate donor cells for inducing iPSCs.

PMID- 24738970
TI  - A Case of Successful Use of Hypnosis in the Treatment of Parasomnia Overlap
      Disorder.
AB  - A young male patient was successfully treated for parasomnia overlap disorder
      (POD) using hypnosis. In 2006, this 16-year-old patient underwent a clinical
      evaluation for episodes of sleep talking, sleepwalking, and dream enactment. This
      initial assessment was followed by polysomnographic evaluation, a brain MRI, and
      three sessions of treatment using hypnosis. From the beginning, until the last
      contact in December 2011, benefits from the hypnotic suggestions were noted and
      documented. 

PMID- 24738971
TI  - Epigenetic regulation of the Igf2/H19 gene cluster.
AB  - Igf2 (insulin-like growth factor 2) and H19 genes are imprinted in mammals; they
      are expressed unevenly from the two parental alleles. Igf2 is a growth factor
      expressed in most normal tissues, solely from the paternal allele. H19 gene is
      transcribed (but not translated to a protein) from the maternal allele. Igf2
      protein is a growth factor particularly important during pregnancy, where it
      promotes both foetal and placental growth and also nutrient transfer from mother
      to offspring via the placenta. This article reviews epigenetic regulation of the
      Igf2/H19 gene-cluster that leads to parent-specific expression, with current
      models including parental allele-specific DNA methylation and chromatin
      modifications, DNA-binding of insulator proteins (CTCFs) and three-dimensional
      partitioning of DNA in the nucleus. It is emphasized that key genomic features
      are conserved among mammals and have been functionally tested in mouse. 'The
      enhancer competition model', 'the boundary model' and 'the chromatin-loop model'
      are three models based on differential methylation as the epigenetic mark
      responsible for the imprinted expression pattern. Pathways are discussed that can
      account for allelic methylation differences; there is a recent study that
      contradicts the previously accepted fact that biallelic expression is accompanied
      with loss of differential methylation pattern. 

PMID- 24738972
TI  - Acute retinal necrosis: clinical features, management and outcomes--a 10 year
      consecutive case series.
AB  - PURPOSE: To determine the viral diagnosis and clinical outcome of eyes with acute
      retinal necrosis (ARN). METHOD: A retrospective analysis was done of 62 eyes of
      53 patients presenting to a tertiary care ophthalmic institute between 1997 and
      2007 with features of ARN. All patients with active disease were started
      immediately on intravenous acyclovir followed by oral antivirals along with
      systemic steroids. A prophylactic laser retinopexy was performed in patients with
      a clear media to areas posterior to the necrotic retina. RESULTS: The aqueous and
      the vitreous sample revealed herpes simplex virus in 19 (30.60%) and varicella
      zoster virus in 28 patients (45.16%). Forty-one (66.12%) eyes had retinal
      detachment. Prophylactic laser photocoagulation was given in 19 (30.64%) eyes.
      Surgical intervention was required in 32 (51.61%) eyes. Favorable functional
      outcome was seen in 28 (45.1%) eyes. CONCLUSION: ARN is a fulminant disorder,
      which if treated early and aggressively gives good results.

PMID- 24738973
TI  - Intragenic CAMTA1 deletions are associated with a spectrum of neurobehavioral
      phenotypes.
AB  - Intragenic copy number variations involving the CAMTA1 (calmodulin-binding
      transcription activator 1) gene have recently been reported in four unrelated
      families with intellectual disability (ID), ataxia, behavioral- and cerebellar
      abnormalities. We report a detailed phenotypic and molecular characterization of
      three individuals with novel intragenic CAMTA1 deletions from two unrelated
      families and compare the findings to those of previously reported patients. Our
      patients had deletions of exons 6-11 and presented with ID, developmental delay
      (DD), attention deficit hyperactivity disorder (ADHD) and constipation. Two
      individuals from one family had also unsteady gait. Consistent phenotypes
      associated with CAMTA1 intragenic rearrangements include ID, speech problems and
      some dysmorphic features whereas neurobehavioral abnormalities are variable. We
      did not observe obvious phenotypic differences between patients with in-frame and
      those with frameshift rearrangements. There is an increased evidence that CAMTA1
      has a role in brain and cerebellar function. CAMTA1 should be added to the
      growing list of genes associated with ID/DD, especially when behavioral problems,
      cerebellar signs, and/or dysmorphism are also present. 

PMID- 24738974
TI  - Infectious lymphadenitis in patients with chronic lymphocytic leukemia/small
      lymphocytic lymphoma: a rare, but important, complication.
AB  - The differential diagnosis of rapidly progressive or symptomatic lymphadenopathy
      in patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL)
      includes infectious lymphadenitis. We studied 286 (9%) of 3040 patients with CLL
      seen between 2003 and 2012 at Mayo Clinic Rochester who had 356 diagnostic lymph
      node biopsies to evaluate rapidly progressive or symptomatic lymphadenopathy.
      Most (85.4%) biopsies showed progressive CLL, 8.9% a second lymphoid malignancy,
      3.9% infectious lymphadenitis, 1.1% reactive adenitis and 0.6% non-hematological
      malignancies. Of the 12 patients (14 biopsies) with infectious lymphadenitis,
      five patients had never been treated for their CLL, and seven had a specific
      microbiological diagnosis (herpes simplex n=3, Cryptococcus neoformans n=1,
      Mycobacterium n=1, coagulase negative Staphylococcus n=2). We conclude that
      infectious lymphadenitis is a rare complication of CLL with clinical
      characteristics similar to progressive CLL and transformation to a more
      aggressive lymphoma. Early recognition and antimicrobial therapy treatment of
      infectious lymphadenitis can be highly effective in these patients.

PMID- 24738975
TI  - Intermittent granulocyte colony-stimulating factor for neutropenia management in
      patients with relapsed or refractory multiple myeloma treated with lenalidomide
      plus dexamethasone.
AB  - Neutropenia is a major dose-limiting toxicity associated with lenalidomide in
      relapsed/refractory multiple myeloma (MM). The optimal dosing schedule of
      granulocyte colony-stimulating factor (G-CSF) is unclear. We developed an
      intermittent G-CSF schedule (4-6 doses per cycle) initiated upon onset of grade 3
      4 neutropenia. Of 216 patients with relapsed/refractory MM treated at our center
      with lenalidomide/dexamethasone on an Expanded Access Program, there was a high
      incidence of grade 3-4 neutropenia (61%) and grade 3-4 infections (37%). Despite
      intermittent G-CSF use in 117 patients, recurrent grade 3-4 neutropenia was
      common (59%), and dose reductions were required in 40% of G-CSF recipients, most
      due to thrombocytopenia. G-CSF recipients had a longer duration on therapy and
      achieved a higher rate and depth of response. Intermittent G-CSF may be an
      effective approach for lenalidomide dose-preservation, which may lead to improved
      outcomes, although it does not prevent infections or thrombocytopenia-related
      dose limitations.

PMID- 24738976
TI  - Matched molecular pair analysis: significance and the impact of experimental
      uncertainty.
AB  - Matched molecular pair analysis (MMPA) has become a major tool for analyzing
      large chemistry data sets for promising chemical transformations. However, the
      dependence of MMPA predictions on data constraints such as the number of pairs
      involved, experimental uncertainty, source of the experiments, and variability of
      the true physical effect has not yet been described. In this contribution the
      statistical basics for judging MMPA are analyzed. We illustrate the connection
      between overall MMPA statistics and individual pairs with a detailed comparison
      of average CHEMBL hERG MMPA results versus pairs with extreme transformation
      effects. Comparing the CHEMBL results to Novartis data, we find that significant
      transformation effects agree very well if the experimental uncertainty is
      considered. This indicates that caution must be exercised for predictions from
      insignificant MMPAs, yet highlights the robustness of statistically validated
      MMPA and shows that MMPA on public databases can yield results that are very
      useful for medicinal chemistry. 

PMID- 24738977
TI  - Efficient synthesis of 1,5-disubstituted carbohydrazones using K2CO3 as a
      carbonyl donor.
AB  - A novel reaction that generates 1,5-disubstituted carbohydrazones via the
      carbonylation of tosylhydrazones has been developed. For the first time, the
      inexpensive, readily available, environmentally friendly, and nongaseous
      potassium carbonate is used as the carbonyl donor for the transformation. The
      reaction system exhibited tolerance with various functional groups and affords
      the desired products in good to excellent yields. This reaction is expected to be
      a powerful tool for the synthesis of carbohydrazone compounds. 

PMID- 24738978
TI  - Femtosecond mid-infrared study of the reorientation of weakly hydrogen-bonded
      water molecules.
AB  - We study the hydrogen-bond and reorientation dynamics of weakly hydrogen-bonded
      water molecules by studying their spectral diffusion and anisotropy dynamics with
      polarization-resolved two-color femtosecond mid-infrared spectroscopy. We
      selectively excite weakly hydrogen-bonded water molecules by tuning a relatively
      narrow band excitation pulse far into the high-frequency wing of the O-D stretch
      vibration of HDO molecules in H2O water. We observe that the spectral diffusion
      and the anisotropy both show pronounced biexponential dynamics. On the basis of
      previous work, the fast component of the spectral dynamics with a time constant
      of ~100 fs is assigned to rapid hydrogen-bond switching events. We observed that
      these switching events lead to a pronounced effect on the anisotropy of the
      excited O-D groups, which shows that the spectral relaxation is accompanied by a
      large change of the orientation of the O-D groups. The slow component of the
      spectral relaxation can be assigned to the collective structural reorganization
      of the hydrogen-bond network of liquid water. With increasing temperature, the
      spectral relaxation shows a similar acceleration as the average molecular
      reorientation, showing that these processes are intimately connected. 

PMID- 24738979
TI  - Frontal fibrosing alopecia: a retrospective clinical review of 62 patients with
      treatment outcome and long-term follow-up.
AB  - BACKGROUND: Frontal fibrosing alopecia is a distinctive form of scarring alopecia
      presenting with frontal and temporoparietal recession of the hairline. Its
      etiology remains unknown, and there are no universal treatment guidelines. We
      conducted a retrospective cohort study to define the clinical findings and
      treatment outcomes of 62 patients with frontal fibrosing alopecia, one of the
      largest cohorts to date. METHODS: Data analysis from case notes was performed on
      62 patients with a diagnosis of frontal fibrosing alopecia seen from January 2004
      to March 2012. RESULTS: Except for one male, all patients in this cohort were
      females (80% post-menopausal) and mostly Caucasians (81%). Age at onset was
      between 18 and 81 years. While 35% reported no symptoms, the majority (65%) had
      itching, pain, or burning sensations. All patients had frontal hairline
      recession, and 81% had complete or partial loss of eyebrows. Perifollicular
      erythema and perifollicular hyperkeratosis occurred in 73% and 31%, respectively.
      Associated autoimmune connective tissue diseases were observed in 14% of
      patients. Reduction in symptoms and hairline stabilization were achieved in 97%
      of treated patients with intralesional corticosteroids. Thirty-one percent of
      patients were able to stop treatments and remained in remission for six months to
      six years. CONCLUSION: Frontal fibrosing alopecia is increasingly seen in
      postmenopausal women and rarely in men. Despite the limitations of a
      retrospective study, we conclude early intervention and treatment with
      intralesional triamcinolone acetonide may halt the progression of the disease;
      however, further controlled prospective studies are needed to establish treatment
      guidelines for frontal fibrosing alopecia.

PMID- 24738981
TI  - Assessment of various second-line medications in addition to inhaled
      corticosteroid in asthma patients: a randomized controlled trial.
AB  - Many patients with persistent asthma cannot achieve the treatment goal for asthma
      with a single controller medication. The aim of the present study was to assess
      lung function and rescue medication use in asthma patients receiving four
      different categories of drugs in combination with an inhaled corticosteroid.
      Patients recruited to the study were randomized into four groups to receive
      budesonide with either formoterol, doxofylline, montelukast or tiotropium for a
      period of 3 months. Lung function (i.e. forced expiratory volume in 1 s (FEV1 ))
      and rescue medication use were determined at baseline and on Day 15, 30, 45, 60
      and 90 of treatment. A total of 297 patients completed the study. At baseline, no
      significant differences (P > 0.05) were observed in any of the outcome measures.
      Significant within-group improvement in FEV1 was observed in all groups. On Day
      90, between-group differences showed that the improvement in FEV1 was
      significantly (P < 0.05) higher for patients receiving budesonide + formoterol,
      followed by budesonide + montelukast and budesonide + doxofylline, and least for
      those receiving budesonide + tiotropium. Similarly, within- and between-group
      comparisons showed significant (P < 0.05) reductions in rescue medication use in
      all groups. However, the magnitude of the decrease was greater in the budesonide
      + formoterol group, followed by the budesonide + montelukast, budesonide +
      doxofylline and budesonide + tiotropium groups. Based on our findings, among the
      second-line treatment regimens, budesonide with either montelukast or doxofylline
      was found to be better than budesonide + tiotropium in patients with mild-to
      moderate persistent asthma. Further studies with a longer duration are likely to
      be useful.

PMID- 24738982
TI  - Investigation of Laplace barriers for arrayed electrowetting lab-on-a-chip.
AB  - Partial-post Laplace barriers have been postulated as a means to allow
      electrowetting transport and geometrical reshaping of fluids, followed by the
      preservation of fluid geometry after the electrowetting voltage is removed.
      Reported here is the first investigation of Laplace barriers with the arrayed
      electrodes and splitting/merging transport functions for an electrowetting lab-on
      a-chip. Laplace barriers optimized for 500 * 500 MUm(2) electrodes and 78 MUm
      channel height are shown to provide geometrical control of fluid shape down to
      radii of curvature of ~70 MUm. The Laplace barriers increase the splitting volume
      error, but with proper electrical control, the average error in the split volume
      is reduced to 5%. Improved programmable fluid storage in droplets or reservoirs
      and continuous channel flow are also shown. This work confirms the potential
      benefits of Laplace barriers for lab-on-a-chip and also reveals the unique
      challenges and operation requirements for Laplace barriers in lab-on-a-chip
      applications.

PMID- 24738983
TI  - Subcellular localization of rice acyl-CoA-binding proteins (ACBPs) indicates that
      OsACBP6::GFP is targeted to the peroxisomes.
AB  - Acyl-CoA-binding proteins (ACBPs) show conservation at the acyl-CoA-binding (ACB)
      domain which facilitates binding to acyl-CoA esters. In Arabidopsis thaliana, six
      ACBPs participate in development and stress responses. Rice (Oryza sativa) also
      contains six genes encoding ACBPs. We investigated differences in subcellular
      localization between monocot rice and eudicot A. thaliana ACBPs. The subcellular
      localization of the six OsACBPs was achieved via transient expression of green
      fluorescence protein (GFP) fusions in tobacco (Nicotiana tabacum) epidermal
      cells, and stable transformation of A. thaliana. As plant ACBPs had not been
      reported in the peroxisomes, OsACBP6::GFP localization was confirmed by transient
      expression in rice sheath cells. The function of OsACBP6 was investigated by
      overexpressing 35S::OsACBP6 in the peroxisomal abc transporter1 (pxa1) mutant
      defective in peroxisomal fatty acid beta-oxidation. As predicted, OsACBP1::GFP
      and OsACBP2::GFP were localized to the cytosol, and OsACBP4::GFP and OsACBP5::GFP
      to the endoplasmic reticulum (ER). However, OsACBP3::GFP displayed subcellular
      multi-localization while OsACBP6::GFP was localized to the peroxisomes.
      35S::OsACBP6-OE/pxa1 lines showed recovery in indole-3-butyric acid (IBA)
      peroxisomal beta-oxidation, wound-induced VEGETATIVE STORAGE PROTEIN1 (VSP1)
      expression and jasmonic acid (JA) accumulation. These findings indicate a role
      for OsACBP6 in peroxisomal beta-oxidation, and suggest that rice ACBPs are
      involved in lipid degradation in addition to lipid biosynthesis. 

PMID- 24738984
TI  - Quantum dynamics of the reaction H((2)S) + HeH(+)(X(1)Sigma(+)) ->
      H2(+)(X(2)Sigmag(+)) + He((1)S) from cold to hyperthermal energies: time
      dependent wavepacket study and comparison with time-independent calculations.
AB  - We present the adiabatic quantum dynamics of the proton-transfer reaction H((2)S)
      + HeH(+)(X(1)Sigma(+)) -> H2(+)(X(2)Sigmag(+)) + He((1)S) on the HeH2(+)
      X(2)Sigma(+) RMRCI6 (M = 6) PES of C. N. Ramachandran et al. ( Chem. Phys. Lett.
      2009, 469, 26). We consider the HeH(+) molecule in the ground vibrational
      rotational state and obtain initial-state-resolved reaction probabilities and the
      ground-state cross section sigma0 and rate constant k0 by propagating time
      dependent, coupled-channel, real wavepackets (RWPs) and performing a flux
      analysis. Three different wavepackets are propagated to describe the wide range
      of energies explored, from cold (0.0001 meV) to hyperthermal (1000 meV) collision
      energies, and in a temperature range from 0.01 to 2000 K. We compare our time
      dependent results with the time-independent ones by D. De Fazio and S. Bovino et
      al., where De Fazio carried out benchmark coupled-channel calculations whereas
      Bovino et al. employed the negative imaginary potential and the centrifugal
      sudden approximations. The RWP cross section is in good agreement with that by De
      Fazio, except at the lowest collision energies below ~0.01 meV, where the former
      is larger than the latter. However, neither the RWP and De Fazio results possess
      the huge resonance in probability and cross section at 0.01 meV, found by Bovino
      et al., who also obtained a too low sigma0 at high energies. Therefore, the RWP
      and De Fazio rate constants compare quite well, whereas that by Bovino et al. is
      in general lower.

PMID- 24738986
TI  - Cytochrome P4502E1 inhibitor, a potential oxidative stress regulator in liver
      diseases.

PMID- 24738985
TI  - Asymmetric functional organozinc additions to aldehydes catalyzed by 1,1'-bi-2
      naphthols (BINOLs).
AB  - Chiral alcohols are ubiquitous in organic structures. One efficient method to
      generate chiral alcohols is the catalytic asymmetric addition of a carbon
      nucleophile to a carbonyl compound since this process produces a C-C bond and a
      chiral center simultaneously. In comparison with the carbon nucleophiles such as
      an organolithium or a Grignard reagent, an organozinc reagent possesses the
      advantages of functional group tolerance and more mild reaction conditions.
      Catalytic asymmetric reactions of aldehydes with arylzincs, vinylzincs, and
      alkynylzincs to generate functional chiral alcohols are discussed in this
      Account. Our laboratory has developed a series of 1,1'-bi-2-naphthol (BINOL)
      based chiral catalysts for the asymmetric organozinc addition to aldehydes. It is
      found that the 3,3'-dianisyl-substituted BINOLs are not only highly
      enantioselective for the alkylzinc addition to aldehydes, but also highly
      enantioselective for the diphenylzinc addition to aldehydes. A one-step synthesis
      has been achieved to incorporate Lewis basic amine groups into the 3,3'-positions
      of the partially hydrogenated H8BINOL. These H8BINOL-amine compounds have become
      more generally enantioselective and efficient catalysts for the diphenylzinc
      addition to aldehydes to produce various types of chiral benzylic alcohols. The
      application of the H8BINOL-amine catalysts is expanded by using in situ generated
      diarylzinc reagents from the reaction of aryl iodides with ZnEt2, which still
      gives high enantioselectivity and good catalytic activity. Such a H8BINOL-amine
      compound is further found to catalyze the highly enantioselective addition of
      vinylzincs, in situ generated from the treatment of vinyl iodides with ZnEt2, to
      aldehydes to give the synthetically very useful chiral allylic alcohols. We have
      discovered that the unfunctionalized BINOL in combination with ZnEt2 and
      Ti(O(i)Pr)4 can catalyze the terminal alkyne addition to aldehydes to produce
      chiral propargylic alcohols of high synthetic utility. The reaction was conducted
      by first heating an alkyne with ZnEt2 in refluxing toluene to generate an
      alkynylzinc reagent, which can then add to a broad range of aldehydes at room
      temperature in the presence of BINOL and Ti(O(i)Pr)4 with high
      enantioselectivity. It was then found that the addition of a catalytic amount of
      dicyclohexylamine (Cy2NH) allows the entire process to be conducted at room
      temperature without the need to generate the alkynylzincs at elevated
      temperature. This BINOL-ZnEt2-Ti(O(i)Pr)4-Cy2NH catalyst system can be used to
      catalyze the reaction of structurally diverse alkynes with a broad range of
      aldehydes at room temperature with high enantioselectivity and good catalytic
      activity. The work described in this Account demonstrates that BINOL and its
      derivatives can be used to develop highly enantioselective catalysts for the
      asymmetric organozinc addition to aldehydes. These processes have allowed the
      efficient synthesis of many functional chiral alcohols that are useful in organic
      synthesis.

PMID- 24738987
TI  - Author's Reply.

PMID- 24738988
TI  - Meta-analysis of prevention of surgical site infections following incision
      closure with triclosan-coated sutures: robustness to new evidence.
AB  - BACKGROUND: A systematic literature review (SLR) and meta-analysis of surgical
      site infections (SSIs) after surgical incision closure with triclosan-coated
      sutures (TS) compared with non-antibacterial coated sutures (NTS) published
      previously by the authors suggested that fewer SSIs occurred in the TS study arm.
      However, the results were vulnerable to the removal of one key randomized
      controlled trial (RCT) because of insufficient data. Furthermore, recently
      published RCTs highlighted the need for an update of the SLR to challenge the
      robustness of results. METHODS: The protocol for the new SLR included more
      stringent tests of robustness than used initially and the meta-analysis was
      updated with the results of two new RCTs as well as the count of patients and
      SSIs by U.S. Centers for Disease Control and Prevention (CDC) incision class.
      RESULTS: The updated SLR included 15 RCTs with 4,800 patients. No publication
      bias was suggested in the analysis. The predominant effect estimated a relative
      risk of 0.67 (95% CI: 0.54-0.84, p=0.00053) with an overall lower frequency of
      SSI in the TS arm than in the NTS arm. RESULTS were robust to sensitivity
      analysis. CONCLUSIONS: The two additional peer-reviewed double-blind RCTs of this
      update confirmed the predominant effect found in the authors' previous meta
      analysis and established the robustness of conclusions that were lacking
      previously. This SLR and meta-analysis showed that the use of triclosan
      antimicrobial sutures reduced the incidence of SSI after clean, clean
      contaminated, and contaminated surgery. The two additional peer-reviewed double
      blind RCTs reinforced the evidence level of this SLR (CEBM level 1a).

PMID- 24738989
TI  - Cooperative effect of anion and mole ratio on the coordination modes of an NO2S3
      donor macrocycle.
AB  - Synthesis of an NO2S3-macrocycle (L) incorporating a pyridine subunit and its
      anion and/or mole ratio-dependent coordination modes in the formations of
      mercury(II) complexes is reported. When the mercury(II) salts with different
      anions (ClO4(-) or Br(-)) were reacted with L, the Hg(ClO4)2 afforded a typical
      endocyclic complex [HgL](ClO4)2 (1). Meanwhile, the HgBr2 gave an exocyclic
      complex [HgLBr2] (2) in which the metal ion exists outside the macrocyclic
      cavity. The observed anion effect on the coordination modes can be explained by
      the anion coordination ability toward the metal cation. In the mole ratio
      variation experiments, notably, the use of 1.5 equiv or above of HgBr2 in the
      same reaction condition gave a unique endo/exocyclic dumbbell-type complex 3,
      [Hg4L2Br6][Hg2Br6]. However, the formation of the endocyclic Hg(ClO4)2 complex 1
      shows no mole ratio dependency. To monitor the observed mole ratio-dependent
      exocoordination products as well as their reactivities and reversibility,
      systematic powder X-ray diffraction (PXRD) analysis was also applied. From single
      crystal X-ray and PXRD analyses, it was found that endocyclic complex 1 is not
      reactive, but complexes 2 and 3 are reactive and show the reversibility between
      them in the presence of the corresponding reactants. 

PMID- 24738990
TI  - Faunistic inventory of spheciformes wasps at three protected areas in Portugal.
AB  - The importance of considering insects in the protection of biodiversity has been
      recently recognized. However, despite the importance of Spheciformes wasps
      (Hymenoptera: Ampulicidae, Sphecidae and Crabronidae) in natural ecosystems and
      their potential as bioindicators, the Spheciformes communities in Portugal (part
      of the European biodiversity hotspot) have rarely been studied, and data for
      Portuguese protected areas are scarce. The Spheciformes wasp communities at 3
      protected areas in Portugal, Douro International Natural Park, Serras de Aire e
      Candeeiros Natural Park, and Paul do Boquilobo Nature Reserve, were studied in
      2000 and 2001. During the study, 134 species of Spheciformes belonging to 3
      families, Ampulicidae, Sphecidae, and Crabronidae, were identified. The species
      collected constituted nearly 1/3 of the species known in the Iberian Peninsula,
      42 were new records for Portugal. Additionally, several specimens of 6
      potentially new species were collected. Douro International Natural Park had the
      highest species richness, followed by Serras de Aire e Candeeiros Natural Park
      and Paul do Boquilobo Nature Reserve. All the protected areas studied had species
      that were found exclusively at an individual protected area and species that were
      found to be new records for Portugal. Based on the literature review of the
      geographic distribution, nidification types, and prey orders, it was found that
      most species collected had a Euroasiatic or Mediterranean distribution, species
      with fossorial habits predominated, and the orders/suborders of insects preyed
      upon by most species were Diptera, Orthoptera, Sternorrhyncha, and
      Auchenorrhyncha. This study underscores the importance of including the protected
      areas studied in the conservation of Spheciformes diversity and also suggests
      that insect diversity should be studied separately, as it does not necessarily
      follow the same patterns as other, more studied, groups.

PMID- 24738991
TI  - Altered plasma fibrin clot properties and fibrinolysis in patients with multiple
      myeloma.
AB  - BACKGROUND: Multiple myeloma (MM) is associated with increased risk of venous and
      arterial thromboembolism. Formation of denser and poorly lysable fibrin clots is
      observed in patients with arterial and venous thromboembolism. We investigated
      fibrin clot properties and their determinants in MM patients. MATERIALS AND
      METHODS: Ex vivo plasma fibrin clot permeability, turbidity and susceptibility to
      lysis were evaluated in 106 MM patients at the time of diagnosis vs. 100 age- and
      sex-matched controls. MM patients had lower clot permeability (Ks ), compaction,
      indicating denser fibrin clots, impaired fibrin polymerization with longer lag
      phase and lower final turbidity (D-Dmax ), combined with hypofibrinolysis
      reflected by longer lysis time and slower rate of D-dimer release from fibrin
      clots (D-Drate ) compared with controls (all P < 0.001). RESULTS: Patients with
      IgG MM had lower Ks compared with IgA MM [5.9 (5.1-6.4) vs. 6.3 (5.9-7.2) 10(-9) 
      cm(2) ; P = 0.007] and longer lysis time compared with light-chain-disease
      patients [11.4 (10.9-12.3) vs. 10.7 (9.8-11.9) min; P = 0.022]. Of the fibrin
      variables, only Ks was significantly lower in patients with International Staging
      System (ISS) grade III than in those with ISS grade I and II [5.9 (4.9-6.6) vs.
      6.2 (5.7-6.8) 10(-9)  cm(2) ; P = 0.015]. Multivariate analysis adjusted for age
      and fibrinogen showed that in MM patients elevated peak thrombin levels determine
      Ks and D-Dmax , while thrombin-activatable fibrinolysis inhibitor (TAFI) activity
      predicts Ks , t50% , D-Drate and lag phase. CONCLUSIONS: Our study demonstrates
      prothrombotic fibrin clot phenotype in patients with MM, with a significant
      impact of increased thrombin formation and TAFI activity.

PMID- 24738993
TI  - Aromatase and endometriosis: estrogens play a role.
AB  - Endometriosis is an estrogen-dependent inflammatory disease defined by the growth
      of endometrial stroma and glands outside of the uterus. Epidemiological and
      clinical studies show that estrogen is essential for the growth of endometriosis.
      There are several molecular links between estrogen production and inflammation in
      endometriosis. The enzyme aromatase P450 is expressed aberrantly in endometriosis
      and is stimulated by prostaglandin E2 , resulting in production of estrogen that
      induces prostaglandin E2 expression within endometriotic lesions. Furthermore,
      estrogen promotes the secretion of several inflammatory cytokines and growth
      factors, which contribute to the progression of endometriosis and stimulate
      estrogen production. On the basis of the local estrogen biosynthesis in
      endometriotic implants, nonsteroidal aromatase inhibitors have been successfully
      used to treat pain symptoms caused by endometriosis. These agents do not cause
      the disappearance of endometriosis; they cannot be considered routine treatment
      and should only be administered in adequately controlled clinical studies. 

PMID- 24738992
TI  - Cellular extract facilitates nuclear reprogramming by altering DNA methylation
      and pluripotency gene expression.
AB  - The functional reprogramming of a differentiated cell to a pluripotent state
      presents potential beneficial applications in disease mechanisms and regenerative
      medicine. Epigenetic modifications enable differentiated cells to perpetuate
      molecular memory to retain their identity. Therefore, the aim of this study was
      to investigate the reprogramming modification of yak fibroblast cells that were
      permeabilized and incubated in the extracts of mesenchymal stem cells derived
      from mice adipose tissue [adipose-derived stem cells (ADSCs)]. According to the
      results, the treatment of ADSC extracts promoted colony formation. Moreover,
      pluripotent gene expression was associated with the loss of repressive histone
      modifications and increased global demethylation. The genes Col1a1 and Col1a2,
      which are typically found in differentiated cells only, demonstrated decreased
      expression and increased methylation in the 5'-flanking regulatory regions.
      Moreover, yak fibroblast cells that were exposed to ADSC extracts resulted in
      significantly different eight-cell and blastocyst formation rates of cloned
      embryos compared with their untreated counterparts. This investigation provides
      the first evidence that nuclear reprogramming of yak fibroblast cells is modified
      after the ADSC extract treatment. This research also presents a methodology for
      studying the dedifferentiation of somatic cells that can potentially lead to an
      efficient way of reprogramming somatic cells toward a pluripotent state without
      genetic alteration.

PMID- 24738994
TI  - The impact of parents' sleep quality and hypoglycemia worry on diabetes self
      efficacy.
AB  - Parents of young children with type 1 diabetes (T1D) may experience poor sleep
      quality, possibly impacting their confidence in T1D management. This study
      investigated sleep characteristics among parents of children with T1D and
      relationships among parents' sleep quality, hypoglycemia worry, and diabetes self
      efficacy. As part of baseline assessment for a randomized clinical trial (RCT) to
      promote parental management of T1D, 134 parents of children <= age 6 reported on
      demographics, parent sleep characteristics, hypoglycemia worry, and diabetes self
      efficacy. Parents reported they slept less time than recommended by the National
      Sleep Foundation and endorsed greater global sleep problems than standardized
      norms of healthy adults; one third of parents reported their overall sleep
      quality was "fairly bad" or "very bad." Hypoglycemia worry and parents' sleep
      quality were both significantly related to diabetes self-efficacy, but parents'
      sleep quality did not mediate the relationship of hypoglycemia worry and diabetes
      self-efficacy. Many parents experience disrupted sleep that impacts their
      perceived ability to perform T1D management. Interventions designed to improve
      parental T1D self-efficacy should consider sleep and concerns about children's
      hypoglycemia. 

PMID- 24738995
TI  - Mechanism of inhibition of the GluA1 AMPA receptor channel opening by the 2,3
      benzodiazepine compound GYKI 52466 and a N-methyl-carbamoyl derivative.
AB  - 2,3-Benzodiazepine derivatives, also known as GYKI compounds, represent a group
      of the most promising synthetic inhibitors of alpha-amino-3-hydroxy-5-methyl-4
      isoxazolepropionic acid (AMPA) receptors. Here we investigate the mechanism of
      inhibition of the GluA1 channel opening and the site of inhibition by GYKI 52466
      and its N-3 methyl-carbamoyl derivative, which we term as BDZ-f. GluA1 is a key
      AMPA receptor subunit involved in the brain function. Excessive activity and
      elevated expression of GluA1, however, has been implicated in a number of
      neurological disorders. Using a laser-pulse photolysis technique, which provides
      ~60 MUs resolution, we measured the effect of these inhibitors on the rate of
      GluA1 channel opening and the amplitude of the glutamate-induced whole-cell
      current. We found that both compounds inhibit GluA1 channel noncompetitively.
      Addition of an N-3 methyl-carbamoyl group to the diazepine ring with the
      azomethine feature (i.e., GYKI 52466) improves the potency of the resulting
      compound or BDZ-f without changing the site of binding. This site, which we
      previously termed as the "M" site on the GluA2 AMPA receptor subunit, therefore
      favorably accommodates an N-3 acylating group. On the basis of the magnitude of
      the inhibition constants for the same inhibitors but different receptors, the "M"
      sites on GluA1 and GuA2 are different. Overall, the "M" site or the binding
      environment on GluA2 accommodates the same compounds better, or the same
      inhibitors show stronger potency on GluA2, as we have reported previously [ Wang
      et al. Biochemistry ( 2011 ) 50 , 7284 - 7293 ]. However, acylating the N-3
      position to occupy the N-3 side pocket of the "M" site can significantly narrow
      the difference and improve the potency of a resulting compound on GluA1. 

PMID- 24738996
TI  - Optimization of culture medium for anaerobic production of rhamnolipid by
      recombinant Pseudomonas stutzeri Rhl for microbial enhanced oil recovery.
AB  - Response surface methodology was employed to enhance the anaerobic production of
      rhamnolipid by recombinant Pseudomonas stutzeri Rhl. Glycerol is a promising
      carbon source used to anaerobically produce rhamnolipid. In a Plackett-Burman
      design, glycerol, KH2 PO4 and yeast extract were significant factors. The
      proposed optimized medium contained the following: 46.55 g l(-1) glycerol; 3 g l(
      1) NaNO3 ; 5.25 g l(-1) K2 HPO4 .3H2 O; 5.71 g l(-1) KH2 PO4 ; 0.40 g l(-1) MgSO4
      .7H2 O; 0.13 g l(-1) CaCl2 ; 1.0 g l(-1) KCl; 1.0 g l(-1) NaCl; and 2.69 g l(-1)
      yeast extract. Using this optimized medium, we obtained an anaerobic yield of
      rhamnolipid of 3.12 +/- 0.11 g l(-1) with a 0.85-fold increase. Core flooding
      test results also revealed that Ps. stutzeri Rhl grown in an optimized medium
      enhanced the oil recovery efficiency by 15.7%, which was 6.6% higher than in the
      initial medium. Results suggested that the optimized medium is a promising
      nutrient source that could effectively mobilize oil by enhancing the in situ
      production of rhamnolipid. SIGNIFICANCE AND IMPACT OF THE STUDY: The ex situ
      application of rhamnolipid for microbial enhanced oil recovery (MEOR) is costly
      and complex in terms of rhamnolipid production, purification and transportation.
      Compared with ex situ applications, the in situ production of rhamnolipid in
      anaerobic oil reservoir is more advantageous for MEOR. This study is the first to
      report the anaerobic production optimization of rhamnolipid. Results showed that
      the optimized medium enhanced not only the anaerobic production of rhamnolipid
      but also crude oil recovery.

PMID- 24738997
TI  - Clinical Patterns of Uveitis in an Iranian Tertiary Eye-care Center.
AB  - PURPOSE: This study aimed to analyze the clinical patterns and etiology of
      uveitis in Isfahan, Iran. METHODS: In this descriptive research, the records of
      2016 patients with uveitis referred to a tertiary eye care centers were examined.
      Age, sex, clinical and anatomical features, and etiology of disease were recorded
      and analyzed. RESULTS: The mean age of onset of uveitis was 33.76 years and the
      women/men ratio was 1.2/1.0. Anterior uveitis was the most common (42.9%) type
      followed by posterior (21.4%), intermediate (19.3%), and pan uveitis (16.31%).
      Noninfectious causes had more roles (76.5%) in the etiology of uveitis. A total
      of 43.9% of the patients had unknown etiology (idiopathic). The most common known
      etiologies were toxoplasmosis, Behcet disease and Fuchs heterochromic
      iridiocyclitis (FHI), respectively. In 15.6%, there was an underlying systemic
      disease. CONCLUSION: There were some differences in the clinical and etiologic
      pattern of uveitis in Isfahan. Environmental, genetic, and geographical factors
      may contribute to this difference.

PMID- 24738998
TI  - What does advanced practice mean to Australian paediatric pharmacists? A focus
      group study.
AB  - OBJECTIVES: The aim of this study was to explore perceptions and attitudes of
      Australian paediatric pharmacists about advanced pharmacy practice and to
      identify suitable methods of assessment for this level of practice. METHODS: Four
      focus groups (with 31 participants) were held in 2012 with Australian hospital
      pharmacists who work with children. Written notes and audio recordings were used
      to produce verbatim transcriptions and extract themes. KEY FINDINGS: There was
      consensus across groups that formal recognition of advanced pharmacy practice was
      valuable to the profession and to individuals. Elements should include a strong
      grounding in clinical practice, commitment to education, research and service
      improvement outside the department and institution. A framework for career
      development should be used to describe the levels of practice leading to advanced
      practice. Assessment should involve multiple separate criteria, and incorporate
      direct observation, peer review and a professional portfolio. Postgraduate
      qualifications are desirable but not considered essential. Different knowledge
      and skills are required in paediatrics; however, the definition of advanced
      practice remains the same. CONCLUSIONS: Recognition of advanced practice is
      valuable for the profession and for individuals. Multiple methods of assessment
      should be used. Specialty areas such as paediatrics can be defined and assessed
      similar to other specialties, with acknowledgement of the specific paediatric
      knowledge and skills required.

PMID- 24738999
TI  - Spontaneous bruising overlying a subcutaneous swelling: pleomorphic hyalinizing
      angiectatic tumor, a relatively new entity of intermediate malignancy.

PMID- 24739000
TI  - Electron transport properties of diarylethene photoswitches by a simplified NEGF
      DFT approach.
AB  - A homemade program called FOXY has been used for the theoretical investigation on
      the conducting properties of two diarylethene based molecules, which, according
      to recent literature data, can act as photoswitches. FOXY uses a simplified
      method relying on NEGF theory coupled to DFT calculations and using a suitable
      electric field to mimic the bias voltage, together with a simple representation
      of the electrodes. The results confirm the experimental findings and are
      rationalized by analyzing the space extension of the pertinent molecular orbitals
      in the ON and OFF electronic states and confirm the FOXY program as a cheap and
      reliable code to be used in the field of molecular electronics. 

PMID- 24739003
TI  - Complete mitochondrial genome of the Blue Eared Pheasant, Crossoptilon auritum
      (Galliformes: Phasianidae).
AB  - The circular mitochondrial genome of Crossoptilon auritum is 16,687 bp in length,
      containing 13 protein-coding genes (PCGs), 2 ribosomal RNA genes, 22 transfer RNA
      (tRNA) genes, and a putative control region. All of the genes encoded on the H
      strand, except for one PCG (nad6) and eight tRNA genes (tRNA(Gln), tRNA (Ala),
      tRNA (Asn), tRNA(Cys), tRNA(Tyr), tRNA(Ser)((UCN)), tRNA(Pro), and tRNA(Glu)), as
      found in many other birds' mitochondrial genomes. All of these PCGs are initiated
      with ATG, except for cox1 and nad5, which began with GTG, while stopped by four
      types of stop codons. All tRNA genes have the potential to fold into typical
      clover-leaf structure. Phylogenetic analysis indicated that the genus
      Crossoptilon was the sister of the genus Lophura.

PMID- 24739001
TI  - Is there an association between periodontitis and hypertension?
AB  - Cardiovascular diseases are the leading cause of deaths. Also, cardiovascular
      risk factors start the atherosclerotic process, which leads to cardiovascular
      diseases. Nowadays, periodontal disease can also be considered another
      cardiovascular risk factor. It involves inflammatory, immunological and humoral
      activities, which induce the production of proinflammatory cytokines and the
      destruction of the epithelium. This allows the entry of endotoxins and exotoxins
      in the bloodstream, which may contribute to atherogenesis and thromboembolic
      events. There is also direct invasion of the vessel wall by oral pathogens,
      triggering an inflammatory response that produces endothelial dysfunction. In
      hypertension, changes in microcirculation can cause ischemia in the periodontium,
      which favors periodontal disease. Moreover, endothelial dysfunction promotes the
      formation of atherosclerotic plaque and the development of lesions in target
      organs. Periodontitis has also been associated with insulin resistance and a
      higher risk for the metabolic syndrome, which is characterized by oxidative
      stress. This seems to act as a common link to explain the relationship between
      each component of the metabolic syndrome (including hypertension) and
      periodontitis. This article will discuss clinical and experimental evidence, as
      well as possible pathophysiologic mechanisms and links involved in the
      relationship among periodontal disease, hypertension and cardiovascular disease. 

PMID- 24739004
TI  - Mitochondrial DNA sequence of Culter compressocorpus.
AB  - In this study, the complete mitochondrial genome of Culter compressocorpus was
      detected and annotated. The circular mtDNA molecule was 16,623 bp in length which
      contains 22 transfer RNA genes, 13 protein-coding genes, 2 ribosomal RNA genes,
      and the non-coding control region (D-loop). Its total protein-coding genes
      content is 68.67% in whole mitochondrial genome. The mitochondrial genome can
      contribute to the studies on geographical distribution and genetic diversity of
      C. compressocorpus resources, as well as molecular phylogeny and species
      identification in Cyprinidae.

PMID- 24739005
TI  - Molecular identification of adulteration in mutton based on mitochondrial 16S
      rRNA gene.
AB  - The aim of this study is to set up a protocol for identification of the
      adulteration in mutton based on mitochondrial 16S rRNA gene. The multiplex
      polymerase chain reaction (multi-PCR) assay was carried out to trace the impure
      DNA in mutton. A universal primer pair yielded an approximate 610 bp fragment in
      mutton, pork, duck, chicken, horse and cat meats. The amplicons of multi-PCR
      assay represented the species-specific products, which could be discriminated by
      the size ranging from 106 bp to 532 bp. Subsequently, the authentication of each
      fragment was also confirmed by sequencing. Random analyses of adulterants with
      various meats yielded the identical results to their components, showing the
      suitability of the multi-PCR assay for tracing of adulterant meats with high
      accuracy and precision. This assay was sensitive to detect the species-specific
      DNA in different proportional mixtures of mutton and duck/pork (9.1%-90.9%). In
      conclusion, this multi-PCR assay successfully discriminated the double-, triple-,
      quadruple-, and quintuple-mixtures containing variant counterparts. This method
      will be particularly useful in the detection of mutton adulteration in processed
      foods further.

PMID- 24739006
TI  - Ion Torrent next-generation sequencing reveals the complete mitochondrial genome
      of black and reddish morphs of the Coral Trout Plectropomus leopardus.
AB  - Using Ion Torrent next-generation sequencing (NGS) technology, we sequenced the
      complete mitochondrial genome (mitogenome) of black and reddish morphs of the
      coral trout Plectropomus leopardus. High-throughput sequencing generated a total
      of 958,614 sequence reads covering 164.80 Mb of two mitogenomes with a coverage
      of 4800X. Thirty-seven mitochondrial genes and gene order of P. leopardus was
      quite similar to that of other teleostean fishes. Most genes were either abutted
      or overlapped, and all the protein-coding genes began with an ATG start codon
      except for COX1 and ATP6. The number of stop codon was different for the black
      and reddish P. leopardus. Comparisons between the mitochondrial sequences of the
      two morphs revealed a total of 74 variable sites and one indel. Nucleotide
      diversity across protein-coding gene varied from 0.0006 (16s rRNA) to 0.0070
      (Cytochrome b). As expected, the highest level of nucleotide diversity (0.0291)
      was detected in the control region. Our results demonstrate the NGS technology
      based on Ion torrent platform can be used to assemble the mitogenome of fish
      species.

PMID- 24739007
TI  - Complete mitochondrial genome of the fennec fox (Vulpes zerda).
AB  - In this study, the complete mitochondrial genome of the fennec fox (Vulpes zerda)
      was sequenced using blood samples obtained from a female individual in Shanghai
      wildlife Park. Sequence analysis showed that the content of T (26.7%) in total
      composition was no more than C (27.2%), which is different from most of Canide
      individuals sequenced previously. 

PMID- 24739008
TI  - Adaptive adhesion by a beetle: manipulation of liquid bridges and their breaking
      limits.
AB  - A drop brought into contact with a nearby substrate can wet and spread against
      the substrate, forming a liquid bridge that exerts a capillary force. This force
      due to surface tension can be used to "grab" the substrate, pulling it toward the
      drop. "Wet" adhesion results from the parallel action of an array of small liquid
      bridges. The Florida palm beetle, Hemisphaerota cyanea, uses wet adhesion to
      defend itself against attacking predators by adhering to the palm leaf using an
      array of about 120,000 MUm-sized liquid bridges. The beetle's survival depends on
      the strength of adhesion which, in turn, depends on how liquid bridges break.
      Individual bridges break when they go unstable, according to their response
      curves. However, the ultimate strength of an individual bridge depends on the
      class of disturbances to which it is subjected, and it has been speculated that
      the beetle may have some control over this class. The authors experimentally
      study families of liquid bridge equilibria for their breaking limits when
      subjected to constant-length (L) and constant-force (F) disturbances. While to
      control constant-L disturbances is straightforward, to apply and control constant
      F disturbances on a liquid bridge requires more ingenuity. The authors introduce
      an apparatus with a lever-arm and a ball-bearing slide. The authors then compare
      our experimentally measured bridge response curves to the force trace from
      experiments on the beetle (prior literature) to infer the mode of beetle
      detachment. Under normal loads, the beetle detaches as a constant-L instability
      for smaller loads and as a constant-F instability for larger loads. The beetle's
      ability to adjust the type and magnitude of loading in real time is not only
      crucial to its survival but has implications for the design of various
      engineering devices.

PMID- 24739009
TI  - Biomimetic surface modification with bolaamphiphilic archaeal tetraether lipids
      via liposome spreading.
AB  - Through investigations of the self-assembly behavior of three different
      tetraether lipids, the authors successfully established a solid supported,
      biomimetic tetraether lipid membrane via liposome spreading. These
      bolaamphiphilic lipids are the main compound in membranes of archaea,
      extremophile microorganisms, which underwent an enormous adaptation to extreme
      conditions in their natural environment with regard to temperature, pH, and high
      salt concentrations. Starting from a mathematical point of view, the authors
      calculated hydrophilic-lipophilic balance values for each lipid and recognized a
      wide difference in self-assembly potentials relying on size and hydrophilic
      properties of the lipid head groups. These results were in good accordance with
      data generated by lipid experiments at the air-water interface applying a
      Langmuir-Blodgett film balance so that the self-assembly potential of two
      different tetraether lipids was found to be sufficient to form stable liposomes
      in aqueous media. Liposomes composed of the main phospholipid of the archaea
      strain Sulfolobus acidocaldarius fused covalently on silanized glass substrates
      and formed a monomolecular lipid layer with upright standing molecules at film
      consistent thicknesses of approximately 5 nm determined by ellipsometry and
      atomic force microscopy. This work can be considered as a basic strategy to find
      optimized lipid properties in terms of liposome formation and spreading in water,
      and it is the first report about archaeal liposome fusing on surfaces to
      establish a solid supported lipid monolayer.

PMID- 24739010
TI  - Immobilized laminin concentration gradients on electrospun fiber scaffolds for
      controlled neurite outgrowth.
AB  - Neuronal process growth is guided by extrinsic environmental cues such as
      extracellular matrix (ECM) proteins. Recent reports have described that the
      growth cone extension is superior across gradients of the ECM protein laminin
      compared to growth across uniformly distributed laminin. In this work, the
      authors have prepared gradients of laminin on aligned electrospun nanofibers for
      use as substrates for neuronal growth. The substrates therefore presented both
      topographical and chemical guidance cues. Step gradients were prepared by the
      controlled robotic immersion of plasma-treated polycaprolactone fibers reacted
      with N-hydroxysuccinimide into the protein solution. The gradients were analyzed
      using x-ray photoelectron spectroscopy and confocal laser scanning microscopy.
      Gradients with a dynamic range of protein concentrations were successfully
      generated and neurite outgrowth was evaluated using neuronlike pheochromocytoma
      cell line 12 (PC12) cells. After 10 days of culture, PC12 neurite lengths varied
      from 32.7 +/- 14.2 MUm to 76.3 +/- 9.1 MUm across the protein concentration
      gradient. Neurite lengths at the highest concentration end of the gradient were
      significantly longer than neurite lengths observed for cells cultured on samples
      with uniform protein coverage. Gradients were prepared both in the fiber
      direction and transverse to the fiber direction. Neurites preferentially aligned
      with the fiber direction in both cases indicating that fiber alignment has a more
      dominant role in controlling neurite orientation, compared to the chemical
      gradient.

PMID- 24739011
TI  - Mephedrone, methylone and 3,4-methylenedioxypyrovalerone (MDPV) induce
      conditioned place preference in mice.
AB  - During the last decade, there has been a worldwide increase in popularity and
      abuse of synthetic cathinones. Common ingredients of the so-called bath salts
      include mephedrone, methylone and 3,4-methylenedioxypyrovalerone (MDPV).
      Relatively little information about the pharmacology and addiction potential of
      these drugs is available. We used the conditioned place preference (CPP) paradigm
      to explore the reinforcing effects of three different synthetic cathinones. The
      primary aim of this study was to investigate whether mephedrone, methylone and
      MDPV induce CPP in mice. The secondary aims were to investigate a possible dose
      response CPP and whether the synthetic cathinones induce higher CPP than
      amphetamine at equal dose. C57BL/6 mice were conditioned to mephedrone,
      methylone, MDPV and amphetamine at doses of 0.5, 2, 5, 10 or 20 mg/kg (i.p.).
      During the conditioning, the mice received two training sessions per day for 4
      days. All four tested drugs showed a significant place preference compared with
      controls. Mice conditioned with MDPV (5 and 10 mg/kg) displayed a greater
      preference score compared to mice conditioned with amphetamine (5 and 10 mg/kg).
      Our findings show that mephedrone, methylone and MDPV produce CPP equal or higher
      than amphetamine strongly suggesting addictive properties. Given the public
      health concern of abuse, future pharmacological studies are necessary to fully
      understand the effects of these drugs. 

PMID- 24739012
TI  - Tumour necrosis factor-alpha inhibition with lenalidomide alleviates tissue
      oxidative injury and apoptosis in ob/ob obese mice.
AB  - Lenalidomide (Revlimid; Selleck Chemicals, Houston, TX, USA), an analogue of
      thalidomide, possesses potent cytokine modulatory capacity through inhibition of
      cytokines such as tumour necrosis factor (TNF)-alpha, a cytokine pivotal for the
      onset and development of complications in obesity and diabetes mellitus. The
      present study was designed to evaluate the effect of lenalidomide on oxidative
      stress, protein and DNA damage in multiple organs in an ob/ob murine model of
      obesity. To this end, C57BL/6 lean and ob/ob obese mice were administered
      lenalidomide (50 mg/kg per day, p.o.) for 5 days. Oxidative stress, protein and
      DNA damage were assessed using the conversion of reduced glutathione (GSH) to
      oxidized glutathione (GSSG), carbonyl formation and Comet assay, respectively.
      Apoptosis was evaluated using caspase 3 activity, and levels of Bax, Bcl-2, Bip,
      caspase 8, caspase 9 and TNF-alpha were assessed using western blot analysis.
      Lenalidomide treatment did not affect glucose clearance in lean or ob/ob mice.
      Obese mice exhibited a reduced GSH/GSSG ratio in the liver, gastrocnemius
      skeletal muscle and small intestine, as well as enhanced protein carbonyl
      formation, DNA damage and caspase 3 activity in the liver, kidney, skeletal
      muscle and intestine; these effects were alleviated by lenalidomide, with the
      exception of obesity-associated DNA damage in the liver and kidney. Western blot
      analysis revealed elevated TNF-alpha, Bax, Bcl-2, Bip, caspase 8 and caspase 9 in
      ob/ob mice with various degrees of reversal by lenalidomide treatment. Together,
      these data indicate that lenalidomide protects against obesity-induced tissue
      injury and protein damage, possibly in association with antagonism of cytokine
      production and cytokine-induced apoptosis and oxidative stress.

PMID- 24739013
TI  - Artefactual skin lesions in children and adolescents: review of the literature
      and two cases of factitious purpura.
AB  - BACKGROUND: Self harm is a great diagnostic and treatment challenge. In addition,
      psychocutaneous conditions are rare in the pediatric population and may therefore
      be misdiagnosed. Dermatitis artefacta is a psychocutaneous syndrome, which is a
      subgroup of the general spectrum of self-inflicted skin lesions. Dermatitis
      artefacta encompasses an array of different clinical manifestations, including
      purpura. Factitious purpura has rarely been reported in children. METHODS: Case
      report and review of the literature. RESULTS: We describe two Caucasian patients
      (9-year-old boy and 10-year-old girl) with striking purpuric lesions diagnosed as
      factitious purpura. The clinical lesions were similar, but the underlying
      psychological problems differed significantly (depression and stress). The
      current state of knowledge of dermatitis artefacta in children and adolescents
      was reviewed. CONCLUSION: The presence of purpura in children and adolescents
      typically causes extensive intervention programs due to the possible serious
      pathological consequences. The two cases demonstrate a need for a high degree of
      attention to psychological disturbances, lesional evolution, and distribution
      once the suspicion is established.

PMID- 24739014
TI  - Pregnant woman with non-comatose autoimmune acute liver failure in the second
      trimester rescued using medical therapy: A case report.
AB  - We present the case of a 25-year-old woman at 16 weeks of gestation who presented
      with non-comatose autoimmune acute liver failure and was at high risk of
      developing fulminant hepatitis. Predictive formulas indicated a high probability
      of developing fulminant hepatitis. Unenhanced computed tomography showed marked
      hepatic atrophy and broadly heterogeneous hypoattenuating areas. The course of
      her illness was subacute, and the etiology of liver injury was unclear.
      Considering all of the above, we predicted a poor prognosis. Plasma exchange (PE)
      and continuous hemodiafiltration (CHDF) therapy were initiated just after
      admission. A few days after admission, a high titer (*80) of antinuclear antibody
      was noted. Because autoimmune hepatitis (AIH) was considered a cause of liver
      failure, treatment with moderate prednisolone (30 mg/day) doses was
      administrated, with careful consideration of her pregnancy. Thereafter, her
      laboratory findings and clinical course gradually improved without the need for
      liver transplantation. A liver biopsy at 18 days after admission indicated a
      diagnosis of AIH. She continued the pregnancy and delivered a healthy baby
      without any complications. Eventually, prednisolone doses were decreased to 10
      mg, after which her liver function worsened. The second liver biopsy also
      indicated a diagnosis of AIH. Accordingly, low-dose prednisolone and azathioprine
      doses (50 mg/day) were administrated to recover her liver function, after which
      her liver function regained normalcy. This case illustrates that a pregnant woman
      with non-comatose autoimmune acute liver failure in the first or second trimester
      of pregnancy and her fetus can be rescued by PE/CHDF therapy and safe moderate
      doses of prednisolone. 

PMID- 24739017
TI  - Vibrational spectroscopy of Co+(CH4)n and Ni+(CH4)n (n = 1-4).
AB  - Vibrational spectra of M(+)(CH4)m(Ar)(3-m) and M(+)(CH4)n (M = Co, Ni; m = 1, 2;
      n = 3, 4) in the C-H stretching region (2500-3100 cm(-1)) are measured using
      photofragment spectroscopy, monitoring the loss of argon or methane. Interaction
      with the metal leads to large red shifts in the C-H stretches for proximate
      hydrogens. The extent of this shift is sensitive to the coordination (eta(2) vs
      eta(3)) and to the metal-methane distance. The structures of the complexes are
      determined by comparing measured spectra with those calculated for candidate
      structures at the B3LYP/6-311++G(3df,3pd) level. Binding energies are also
      computed using the CAM-B3LYP functional. In all cases, CH4 shows eta(2)
      coordination to the metal. The m = 1 complexes show very large red shifts of 370
      cm(-1) (for M = Co) and 320 cm(-1) (for M = Ni) in the lowest C-H stretch,
      relative to the symmetric stretch of free CH4. They adopt a C2v structure with
      the heavy atoms and proximate hydrogen atoms coplanar. The m = 2 complexes have
      slightly reduced red shifts, and Tee-shaped structures. Both Tee-shaped and
      equilateral (or quasi-equilateral) structures are observed for the n = 3
      complexes. The measured photodissociation onset and significantly reduced
      intensity for low-frequency C-H stretches imply a value of 2650 +/- 50 cm(-1) for
      the binding energy of Ni(+)(CH4)2-CH4. The Co(+)(CH4)4 complexes have two low
      lying structures, quasi-tetrahedral and distorted square-planar, which contribute
      to the rich spectrum. In contrast, the symmetrical, square-planar Ni(+)(CH4)4
      complex is characterized by a very simple vibrational spectrum.

PMID- 24739016
TI  - Performance of Massachusetts Male Aging Study (MMAS) and androgen deficiency in
      the aging male (ADAM) questionnaires in the prediction of free testosterone in
      patients aged 40 years or older treated in outpatient regimen.
AB  - OBJECTIVE: At present, calculated free testosterone assessment is considered as
      the gold standard in diagnosing male hypogonadism. However, this assessment is
      not available for all the individuals diagnosed with decreased testicular
      function. The investigators of this study were, thus, prompted to evaluate
      whether the androgen deficiency in the aging male (ADAM) and the Massachusetts
      Male Ageing Study (MMAS) questionnaires could be used to replace biochemical
      parameters in the diagnosis for hypogonadism in men aged 40 years and above.
      METHODS: We evaluated 460 men, aged 40 years and above, all volunteers of a
      screening program for prostate cancer based at the Hospital de Clinicas of Porto
      Alegre. In this study, we assessed the efficiency of the ADAM and MMAS
      questionnaires in diagnosing Brazilian men with low levels of total, calculated
      free and bioavailable testosterone. RESULTS: The sensitivity of the ADAM
      questionnaire in diagnosing the calculated free testosterone was 73.6%, whereas
      specificity was 31.9%. ADAM could be used to properly classify our cohort into
      normal or hypogonadal individuals in 52.75% of the cases. The sensitivity of the
      MMAS questionnaire was 59.9%, whereas the specificity was 42.9%, resulting in a
      successful classification of 51.4% of the patients. CONCLUSION: The ADAM and MMAS
      questionnaires showed adequate sensitivity in diagnosing male patients with low
      levels of free testosterone. However, because of the lack of specificity, these
      tools cannot replace calculated free testosterone assessments in men aged 40
      years and above.

PMID- 24739018
TI  - Dynamic covalent chemistry approaches toward macrocycles, molecular cages, and
      polymers.
AB  - The current research in the field of dynamic covalent chemistry includes the
      study of dynamic covalent reactions, catalysts, and their applications. Unlike
      noncovalent interactions utilized in supramolecular chemistry, the
      formation/breakage of covalent bonding has slower kinetics and usually requires
      the aid of a catalyst. Catalytic systems that enable efficient thermodynamic
      equilibrium are thus essential. In this Account, we describe the development of
      efficient catalysts for alkyne metathesis, and discuss the application of dynamic
      covalent reactions (mainly imine, olefin, and alkyne metathesis) in the
      development of organic functional materials. Alkyne metathesis is an emerging
      dynamic covalent reaction that offers robust and linear acetylene linkages. By
      introducing a podand motif into the catalyst ligand design, we have developed a
      series of highly active and robust alkyne metathesis catalysts, which, for the
      first time, enabled the one-step covalent assembly of ethynylene-linked
      functional molecular cages. Imine chemistry and olefin metathesis are among the
      most well-established reversible reactions, and have also been our main synthetic
      tools. Various shape-persistent macrocycles and covalent organic polyhedrons have
      been efficiently constructed in one-step through dynamic imine chemistry and
      olefin metathesis. The geometrical features and solubilizing groups of the
      building blocks as well as the reaction kinetics have significant effect on the
      outcome of a covalent assembly process. More recently, we explored the
      orthogonality of imine and olefin metatheses, and successfully synthesized
      heterosequenced macrocycles and molecular cages through one-pot orthogonal
      dynamic covalent chemistry. In addition to discrete molecular architectures,
      functional polymeric materials can also be accessed through dynamic covalent
      reactions. Defect-free solution-processable conjugated polyaryleneethynylenes and
      polydiacetylenes have been prepared through alkyne metathesis polymerization. We
      prepared imine- or ethynylene-linked porous polymer networks, which exhibit
      permanent porosity with high specific surface areas. Our most recent contribution
      is the discovery of a recyclable polyimine material whose self-healing can be
      activated simply by heating or water treatment. The facile access to complex
      functional organic molecules through dynamic covalent chemistry has allowed us to
      explore their exciting applications in gas adsorption/separation, host-guest
      chemistry, and nanocomposite fabrication. It is clear that there are significant
      opportunities for improved dynamic covalent systems and their more widespread
      applications in materials science.

PMID- 24739019
TI  - Breaking down the barriers: a qualitative study to understand child oral health
      in refugee and migrant communities in Australia.
AB  - OBJECTIVE: Australia is an increasingly multicultural nation. Never before has
      the dental workforce been exposed to such language, cultural, religious and
      ethnic diversity. There is evidence that refugee and migrant children experience
      significantly poorer oral health than the nonmigrant population. However, little
      is known about the oral health knowledge, practices and beliefs of parents with
      young children from refugee and migrant backgrounds. The aim of this study was to
      identify the sociocultural influences on child oral health in these communities.
      DESIGN: Participatory and qualitative research methods were utilised.
      Partnerships were established with community agencies representing migrants from
      Iraq, Lebanon and Pakistan. Focus group discussions and semi-structured
      interviews were conducted with community members. Qualitative data were analysed
      thematically, combining focus group and interview data. RESULTS: Over 100 women
      participated in focus groups (n = 11) and semi-structured interviews (n = 7). Key
      findings included the knowledge, beliefs and practices concerning: caries risk
      factors, oral health practices and oral health literacy. Despite mothers'
      knowledge of the major causes of poor oral health - dietary changes, confusion
      about child oral hygiene practices and limited oral health literacy all
      influenced child oral health outcomes. CONCLUSION: This culturally competent
      qualitative study explores the sociocultural factors influencing child oral
      health in refugee and migrant communities. Understanding and acknowledging these
      factors are a prerequisite to determining where and how to intervene to improve
      oral health. Furthermore, it has implications for both dental and non-dental
      health professionals working to reduce health inequalities within such
      communities.

PMID- 24739020
TI  - Sexually dimorphic actions of glucocorticoids: beyond chromosomes and sex
      hormones.
AB  - Sexual dimorphism is a well-documented phenomenon that is observed at all levels
      of the animal kingdom. Historically, sex hormones (testosterone and estrogen)
      have been implicated as key players in a wide array of pathologies displaying
      sexual dimorphism in their etiology and progression. While these hormones clearly
      contribute to sexually dimorphic diseases, other factors may be involved in this
      phenomenon as well. In particular, the stress hormone cortisol exerts
      differential effects in both males and females. The underlying molecular basis
      for the sexually dimorphic actions of glucocorticoids is unknown but clearly
      important to understand, since synthetic glucocorticoids are the most widely
      prescribed medication for the treatment of chronic inflammatory diseases and
      hematological cancers in humans. 

PMID- 24739021
TI  - Model for anodic film growth on aluminum with coupled bulk transport and
      interfacial reactions.
AB  - Films grown through the anodic oxidation of metal substrates are promising for
      applications ranging from solar cells to medical devices, but the underlying
      mechanisms of anodic growth are not fully understood. To provide a better
      understanding of these mechanisms, we present a new 1D model for the anodization
      of aluminum. In this model, a thin space charge region at the oxide/electrolyte
      interface couples the bulk ionic transport and the interfacial reactions. Charge
      builds up in this region, which alters the surface overpotential until the
      reaction and bulk fluxes are equal. The model reactions at the oxide/electrolyte
      interface are derived from the Valand-Heusler model, with modifications to allow
      for deviations from stoichiometry at the interface and the saturation of
      adsorption sites. The rate equations and equilibrium concentrations of adsorbed
      species at the oxide/electrolyte interface are obtained from the reactions using
      Butler-Volmer kinetics, whereas transport-limited reaction kinetics are utilized
      at the metal/oxide interface. The ionic transport through the bulk oxide is
      modeled using a newly proposed cooperative transport process, the counter-site
      defect mechanism. The model equations are evolved numerically. The model is
      parametrized and validated using experimental data in the literature for the rate
      of ejection of aluminum species into the electrolyte, embedded charge at the
      oxide/electrolyte interface, and the barrier thickness and growth rate of porous
      films. The parametrized model predicts that the embedded charge at the
      oxide/electrolyte interface decreases monotonically for increasing electrolyte pH
      at constant current density. The parametrized model also predicts that the
      embedded charge during potentiostatic anodization is at its steady-state value;
      the embedded charge at any given time is equal to the embedded charge during
      galvanostatic anodization at the same current. In addition to simulations of
      anodized barrier films, this model can be extended to multiple dimensions to
      simulate anodic nanostructure growth. 

PMID- 24739022
TI  - An optimal defense strategy for phenolic glycoside production in Populus
      trichocarpa--isotope labeling demonstrates secondary metabolite production in
      growing leaves.
AB  - Large amounts of carbon are required for plant growth, but young, growing tissues
      often also have high concentrations of defensive secondary metabolites. Plants'
      capacity to allocate resources to growth and defense is addressed by the growth
      differentiation balance hypothesis and the optimal defense hypothesis, which make
      contrasting predictions. Isotope labeling can demonstrate whether defense
      compounds are synthesized from stored or newly fixed carbon, allowing a detailed
      examination of these hypotheses. Populus trichocarpa saplings were pulse-labeled
      with 13CO2 at the beginning and end of a growing season, and the 13C signatures
      of phenolic glycosides (salicinoids), sugars, bulk tissue, and respired CO2 were
      traced over time. Half of the saplings were also subjected to mechanical damage.
      Populus trichocarpa followed an optimal defense strategy, investing 13C in
      salicinoids in expanding leaves directly after labeling. Salicinoids turned over
      quickly, and their production continued throughout the season. Salicin was
      induced by early-season damage, further demonstrating optimal defense.
      Salicinoids appear to be of great value to P. trichocarpa, as they command new C
      both early and late in the growing season, but their fitness benefits require
      further study. Export of salicinoids between tissues and biochemical pathways
      enabling induction also needs research. Nonetheless, the investigation of defense
      production afforded by isotope labeling lends new insights into plants' ability
      to grow and defend simultaneously.

PMID- 24739023
TI  - Assessment of core and accessory genetic variation in Rhizobium leguminosarum
      symbiovar trifolii strains from diverse locations and host plants using PCR-based
      methods.
AB  - The nitrogen-fixing symbiosis between Rhizobium leguminosarum and host legumes is
      recognized as a key part of sustainable agriculture. A culture collection
      containing rhizobia isolated from legumes of economic importance in the UK and
      worldwide, maintained at Rothamsted Research for many years, provided material
      for this study. We aimed to develop and validate efficient molecular diagnostics
      to investigate whether the host plant or geographical location had a greater
      influence on the genetic diversity of rhizobial isolates, and the extent to which
      the core bacterial genome and the accessory symbiosis genes located on plasmids
      were affected. To achieve this, core housekeeping genes and those involved in
      symbiosis interactions were sequenced and compared with genome-sequenced strains
      in the public domain. Results showed that some Rh. leguminosarum symbiovar
      trifolii strains nodulating clovers and Rh. leguminosarum sv. viciae strains
      nodulating peas and vicias shared identical housekeeping genes, clover nodule
      isolates from the same location could have divergent symbiosis genes, and others
      isolated on different continents could be very similar. This illustrates the
      likely co-migration of rhizobia and their legume hosts when crops are planted in
      new areas and indicates that selective pressure may arise from both local
      conditions and crop host genotypes. SIGNIFICANCE AND IMPACT OF THE STUDY: The
      nitrogen-fixing symbiosis between Rhizobium leguminosarum and host legumes has
      been recognized as a key part of sustainable agriculture for many years; this
      study provides new tools to study rhizobial biogeography which will be invaluable
      for extending the cultivation of legumes and indicating whether or not
      inoculation is necessary.

PMID- 24739024
TI  - Control of the iridium oxidation state in the hollandite iridate solid solution
      K(1-x)Ir4O8.
AB  - The synthesis and physical properties of the K(1-x)Ir4O8 (0 <= x <= 0.7) solid
      solution are reported. The structure of KIr4O8, solved with single-crystal X-ray
      diffraction at T = 110 K, is found to be tetragonal, space group I4/m, with a =
      10.0492(3) A and c = 3.14959(13) A. A highly anisotropic displacement parameter
      is found for the potassium cation. Density functional theory calculations suggest
      that this anisotropy is due to a competition between atomic size and bond
      valence. KIr4O8 has a significant electronic contribution to the specific heat,
      gamma = 13.9 mJ mol-Ir(-1) K(-2), indicating an effective carrier mass of m*/me ~
      10. Further, there is a magnetic-field-dependent upturn in the specific heat at T
      < 3 K, suggestive of a magnetically sensitive phase transition below T < 1.8 K.
      Resistivity and magnetization measurements show that both end-members of the
      solid solution, KIr4O8 and K(1-x)Ir4O8 (x ~ 0.7), are metallic, with no
      significant trends in the temperature-independent contributions to the
      magnetization. These results are interpreted and discussed in the context of the
      importance of the variability of the oxidation state of iridium. The differences
      in physical properties between members of the K(1-x)Ir4O8 (0 <= x <= 0.7) series
      are small and appear to be insensitive to the iridium oxidation state.

PMID- 24739026
TI  - Increased RBP4 in a human model of activated anti-atherosclerotic and
      antiremodelling defences.
AB  - BACKGROUND: Both increased and decreased levels of the adipokine retinol-binding
      protein 4 (RBP4) have been reported in cardiovascular disease, and levels of RBP4
      have been related to diabetes, metabolic syndrome and cardiovascular risk.
      Recently, clear in vitro and ex vivo vasodilatory and inhibitory of platelet
      activation effects of RBP4 has been shown and a reduced RBP4 level was found in
      high cardiovascular risk patients, suggesting a potential cardiovascular
      protective role for increased levels of RBP4. PATIENTS AND METHODS: Plasma level
      of RBP4 (ELISA) was determined in a cohort of Bartter's and Gitelman's syndrome
      (BS/GS) patients, a human model of endogenous Ang II signalling antagonism and
      activation of anti-atherosclerotic and antiremodelling defenses, the opposite of
      cardiovascular risk patients, and in healthy normotensive subjects. Haem
      Oxygenase (OH)-1 protein level (sandwich immunoassay) as a potential mediator of
      RBP4 stimulation of PI3K/Akt pathway and flow-mediated dilation (FMD) as a
      measure of endothelium (NO)-dependent response have also been measured. RESULTS:
      RBP4 in BS/GS patients (40.59 +/- 15.32 MUg/mL vs. 25.05 +/- 5.56, P = 0.011)
      along with HO-1 protein levels (9.44 +/- 3.09 ng/mL vs. 5.49 +/- 1.04, P = 0.003)
      and FMD (10.52% +/- 2.22 vs. 7.99 +/- 1.13 P = 0.006) were significantly
      increased compared with healthy normotensive subjects. CONCLUSIONS: The increase
      of RBP4 in BS/GS, a human model of endogenous Ang II signalling antagonism and
      activation of anti-atherosclerotic and antiremodelling defenses, the opposite of
      cardiovascular risk patient, found in concert with an increased NO-mediated
      vasodilation and HO-1 levels supports a protective role for this adipokine in
      vascular protection/cardiovascular risk.

PMID- 24739027
TI  - Rodent biology and management.

PMID- 24739028
TI  - A revised picture of the Cu(II)-alpha-synuclein complex: the role of N-terminal
      acetylation.
AB  - alpha-Synuclein (alphaS) is an amyloidogenic intrinsically disordered protein
      implicated in Parkinson's disease, for which copper-mediated pathways of
      neurodegeneration have been suggested. We have employed nuclear magnetic
      resonance, circular dichroism, electrospray ionization mass spectrometry, and
      thioflavin T fluorescence to characterize interactions of Cu(2+) with the
      physiological acetylated form (Ac-alphaS). Significantly, N-terminal acetylation
      abolishes Cu(2+) binding at the high-affinity M1-D2 site present in the
      nonacetylated protein and maintains Cu(2+) interactions around H50/D121.
      Fibrillation enhancement observed at an equimolar Cu(2+) stoichiometry with the
      nonacetylated model does not occur with Ac-alphaS. These findings open new
      avenues of investigation into Cu(2+)-mediated neurodegenerative pathology
      suggested in vivo. 

PMID- 24739030
TI  - Diagnostic accuracy of the SNAP and Spec canine pancreatic lipase tests for
      pancreatitis in dogs presenting with clinical signs of acute abdominal disease.
AB  - OBJECTIVES: To (i) assess the clinical diagnostic accuracy of SNAP canine
      pancreatic lipase (cPL) and specific canine pancreatic lipase (Spec cPL) and (ii)
      assess the agreement of an abnormal test result between SNAP cPL and Spec cPL in
      dogs presenting with acute abdominal disease. DESIGN: Prospective observational
      cohort study. SETTING: University teaching hospital emergency center. ANIMALS:
      Thirty-eight client-owned dogs that presented with acute abdominal disease, with
      a known final diagnosis between March 2009 and April 2010. Dogs were
      retrospectively assigned into 2 groups, dogs with acute pancreatitis (AP) (Group
      1) and dogs without AP (Group 2). INTERVENTIONS: Paired serum samples obtained
      within 24 hours of presentation were analyzed using the SNAP cPL test and Spec
      cPL assay. MEASUREMENTS AND RESULTS: SNAP cPL clinical sensitivity and
      specificity was 82% (9/11 dogs of group 1) and 59% (16/27 dogs of group 2),
      respectively. Spec cPL clinical sensitivity and specificity was 70% (7/10 dogs of
      group 1) and 77% (20/26 dogs of group 2), respectively. Accuracy of the SNAP and
      Spec cPL for a clinical diagnosis of pancreatitis was found to be 66% and 75%,
      respectively. Agreement between a positive SNAP (cPL >= 200 MUg/L) and a clinical
      diagnosis pancreatitis resulted in kappa = 0.33. Agreement between an increased
      Spec (cPL >= 400 MUg/L) and a clinical diagnosis of pancreatitis resulted in a
      kappa = 0.43. The agreement between SNAP and Spec cPL (cPL >= 200 MUg/L) for the
      entire cohort resulted in kappa = 0.78. CONCLUSION: SNAP cPL and Spec cPL results
      may provide a "false positive" diagnosis of pancreatitis in up to 40% of dogs
      presenting with acute abdominal disease. There is good overall agreement between
      SNAP cPL and Spec cPL; however, there were 4/38 dogs with positive SNAP cPL and
      "normal" Spec cPL.

PMID- 24739031
TI  - Thromboelastographic evaluation of hemostatic function in dogs treated for
      crotalid snake envenomation.
AB  - OBJECTIVE: To characterize the overall hemostatic changes in dogs envenomated by
      crotaline snakes via kaolin-activated thromboelastography (TEG), and to determine
      any prognostic/monitoring value from a TEG tracing on presentation, as well as
      during treatment with antivenom therapy. DESIGN: Prospective observational,
      cohort study. SETTING: University teaching hospital and primary emergency
      hospital. ANIMALS: Thirty-eight dogs envenomated by crotaline snakes.
      INTERVENTIONS: TEG tracings were evaluated on presentation to the hospital (pre)
      as well as immediately following (post) and 12 hours (12 h post) after antivenom
      treatment, if administered. MEASUREMENTS AND MAIN RESULTS: At presentation, data
      were available for 38 dogs envenomated by crotaline snakes. Twenty dogs were in
      Group 1 (Antivenin [Crotalidae] Polyvalent antivenom), 12 dogs were in Group 2
      (Antivipmyn antivenom), and 6 dogs in Group 3 that were not treated with
      antivenom. The average number of vials administered to group 1 and 2 were equal
      at 2.2. On presentation, based on a G value < TEG reference range, 15/38 (39%) of
      the dogs had hypocoagulable TEG tracings. There was a significant increase in G
      and MA value from the pre and 12 hour post measurement (P = 0.0001 and 0.0003,
      respectively), as well as from the post to 12 hour post measurement (P = 0.003
      and, 0.014, respectively). During the study, 5 of 38 dogs died (13%) and of the
      dogs that died, 4/5 (80%) had angle and MA equal to zero on presentation. A
      decreased G and MA were significantly associated with mortality (P = 0.02 and
      0.04, respectively). CONCLUSIONS: A hypocoagulable TEG tracing, particularly a
      decreased G value and MA, is associated with an increased mortality in crotaline
      snake envenomation. G and MA also demonstrate a significant increase over
      treatment time.

PMID- 24739032
TI  - Decreased central venous oxygen saturation despite normalization of heart rate
      and blood pressure post shock resuscitation in sick dogs.
AB  - OBJECTIVE: To evaluate traditional and global perfusion parameters in clinical
      canine shock patients, and to evaluate for occult hypoperfusion as evidenced by
      low central venous oxygen saturation or high plasma lactate concentrations in
      clinical patients resuscitated to traditional endpoints. DESIGN: Clinical
      observational trial designed with a 1-year data entry period and patient follow
      up of 28 days posthospital presentation. SETTING: Large, private urban teaching
      hospital, and emergency and critical care center. ANIMALS: Adult canine patients
      presenting to the emergency department with untreated shock. INTERVENTIONS: None.
      MEASUREMENTS AND MAIN RESULTS: Patients received fluid resuscitation to normalize
      perfusion parameters based on physical examination and arterial blood pressure
      (BP). Monitoring of central venous pressure (CVP) and central venous oxygen
      saturation (ScvO2 ) was feasible with current standard of care interventions in
      critically ill, client-owned dogs. Decreased ScvO2 was observed in 37.8% of
      patients resuscitated to normal traditional perfusion parameters. Hyperlactatemia
      was commonly recorded. CONCLUSIONS: Decreased ScvO2 exists in a significant
      proportion of critically ill dogs following standard fluid resuscitation for
      shock, providing a relevant target population for implementation of a more
      standardized early goal-directed therapy bundle in veterinary patients.
      Normalization of heart rate, blood pressure, mentation, and perfusion parameters
      directed by physical examination may be attained despite the persistence of
      significant tissue hypoperfusion and oxygen debt.

PMID- 24739033
TI  - A comparison of the clinical utility of several published formulae for estimated
      osmolality of canine serum.
AB  - OBJECTIVE: To determine the normal osmole gap for 18 previously published
      formulae used to estimate serum osmolality in dogs. DESIGN: Prospective study.
      SETTING: University veterinary medical teaching hospital. ANIMALS: Two hundred
      and fifty client-owned dogs. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS:
      Serum samples were saved and frozen at -80 degrees C after routine biochemical
      analysis as ordered by attending clinicians. An Advanced Micro Osmometer 3300 was
      used to measure serum osmolality. Eighteen distinct formulae previously reported
      in the medical literature were used to calculate the osmolality from the
      biochemical analysis results. The calculated osmolality was then subtracted from
      the measured osmolality to determine the osmole gap. Osmole gaps for azotemic and
      hyperglycemic dogs were compared to those of dogs without azotemia or
      hyperglycemia using each formula. The median measured osmolality for all dogs in
      the study was 302 mOsm/kg (interquartile range 297-307). The osmole gaps varied
      widely depending on the formula used to calculate osmolality and the presence or
      absence of hyperglycemia or azotemia. Eleven formulae led to calculated
      osmolality and osmole gaps that were not statistically different when
      hyperglycemia or azotemia was present. Four out of these 11 formulae resulted in
      osmole gaps near zero. CONCLUSIONS AND CLINICAL RELEVANCE: Multiple formulae
      reported to calculate serum osmolality can be used in the clinical setting, but
      they result in significantly different normal osmole gaps. Clinicians should be
      aware of the specific reference interval for the formula being used. The authors
      recommend the formula 2(Na(+) ) + [glucose/18] + [BUN/2.8] because it is easy to
      use and is reliable even when hyperglycemia or azotemia are present.

PMID- 24739034
TI  - Presumptive cocaine toxicosis in 19 dogs: 2004-2012.
AB  - OBJECTIVE: To characterize the incidence, signalment, presenting complaint,
      history, clinical signs, diagnostic test results, complications, treatment,
      length of hospitalization, and outcome of dogs presenting with presumptive
      cocaine toxicosis. DESIGN: Retrospective study from March 1, 2004 to March 1,
      2012. SETTING: Twenty-four hour urban university veterinary teaching hospital.
      ANIMALS: Nineteen dogs presenting with clinical signs consistent with cocaine
      toxicosis and having a positive urine cocaine test. INTERVENTIONS: None.
      MEASUREMENTS AND MAIN RESULTS: All dogs had neurological abnormalities including
      bilateral mydriasis (11/19 [58%]), hyperexcitability/hyperesthesia (10/19 [53%]),
      ataxia (8/19 [42%]), focal or generalized muscle tremors (8/19 [42%]), reduced
      mental awareness (6/19 [32%]), and seizures (3/19 [16%]). Other signs included
      weakness (7/19 [37%]), vomiting (6/19 [32%]), and lethargy (3/19 [16%]).
      Tachycardia was apparent in 10/19 (53%) dogs, hypertension in 4/19 (21%), and
      hyperthermia in 5/19 (26%). Sinus tachycardia was the only reported cardiac
      arrhythmia. Bloodwork findings included hyperglycemia in 4/19 (21%) dogs, and
      increased plasma lactate concentration in 9/19 (47%). Most dogs (16/19 [84%])
      were hospitalized for supportive care, which generally included isotonic
      crystalloid fluid administration, and treatment with sedative or anxiolytic drugs
      including diazepam, midazolam, acepromazine, and chlorpromazine. Two dogs
      required further anticonvulsant therapy (phenobarbital and propofol) and 1 dog
      was treated with a constant rate infusion of esmolol. All dogs survived to
      discharge, and the median length of hospitalization was 15 hours (10-30 h).
      CONCLUSIONS: Cocaine toxicosis was infrequently suspected. Neurological signs
      predominated, but cardiovascular alterations were also frequently reported.
      Hospitalization for monitoring and supportive care is recommended given the
      potential for life-threatening complications such as seizures, hypertensive
      crisis, and tachyarrhythmias. The prognosis for survival to hospital discharge
      can be good with the appropriate supportive care.

PMID- 24739035
TI  - Acid base, electrolyte, glucose, and lactate values during cardiopulmonary
      resuscitation in dogs and cats.
AB  - OBJECTIVE: To report acid base, electrolyte, glucose, and lactate values
      collected during or immediately after cardiopulmonary resuscitation (CPR) in dogs
      and cats. DESIGN: Retrospective study. SETTING: University Teaching Hospital.
      ANIMALS: Thirty-two dogs and 10 cats. INTERVENTIONS: None. MEASUREMENTS AND MAIN
      RESULTS: Blood gas, electrolyte, glucose, and lactate values measured during CPR
      or within 5 minutes of return of spontaneous circulation (ROSC) were
      retrospectively evaluated. The time of blood collection with respect to the
      occurrence of cardiopulmonary arrest (CPA), the initiation of CPR or ROSC was
      noted. Forty-two venous blood samples were analyzed, 24 collected during CPR and
      18 samples were collected within 5 minutes of ROSC. Metabolic acidosis and
      hyperlactatemia were evident in all samples in the study while an increased PvCO2
      occurred in 88% of samples collected during CPR and in 61% of samples collected
      following ROSC. Hyperkalemia occurred in 65% of all cases, decreased ionized
      calcium was evident in 18%, hypoglycemia was evident in 21% while hyperglycemia
      was evident in 62%. There was no significant difference in any parameter
      evaluated between dogs and cats during CPR. There was no significant difference
      of any variable measured during the first 15 minutes of CPA versus those measured
      more than 15 minutes following CPA. When the values measured during the first 5
      minutes of ROSC were compared to those measured during CPR, the pH and PvO2 were
      significantly lower in the CPR group. CONCLUSIONS: Biochemical abnormalities
      including metabolic acidosis, hyperkalemia, ionized hypocalcemia, hypoglycemia,
      and hyperglycemia can be identified during CPR and immediately following ROSC.
      The therapeutic and prognostic relevance of these changes are yet to be defined
      and may prove to be useful to guide patient management in the future.

PMID- 24739036
TI  - Retrospective evaluation of the use of autologous blood-patch treatment for
      persistent pneumothorax in 8 dogs (2009-2012).
AB  - OBJECTIVE: To describe the clinical course, outcome and success rate of 8 dogs
      with persistent pneumothorax treated with autologous blood-patch pleurodesis
      (ABP). DESIGN: Retrospective case series. SETTING: University teaching hospital
      ANIMALS: Eight client-owned dogs. INTERVENTION: Non-coagulated blood was
      aseptically collected from the jugular vein and injected immediately into the
      pleural cavity of dogs with persistent pneumothorax. MEASUREMENTS AND MAIN
      RESULTS: The procedure was successful in 7 of 8 dogs. The median duration of
      pneumothorax until the ABP was performed was 4 days (range 2-6 days).
      Pneumothorax resolved immediately after 1 treatment in 4 dogs. Pleurodesis was
      repeated once in 3 dogs, and twice in 1 case after which it resolved in 3 of the
      4 dogs. Out of a total of 13 ABP procedures performed in 8 dogs, 5 (62.5%) were
      successful after 1 procedure and the success rate increased to 87.5% after
      additional procedures. One dog failed ABP and was euthanized 3 days later due to
      continued deterioration and a hospital acquired pneumonia. Mild to moderate
      complications occurred in 2 other dogs and resolved in both. CONCLUSIONS: ABP is
      a simple, inexpensive, and relatively safe procedure which can be considered in
      dogs with persistent pneumothorax that have failed conservative or surgical
      management. Infections following ABP were documented in 2 of the 8 dogs and
      resolved in 1 dog.

PMID- 24739041
TI  - SGK3 is an androgen-inducible kinase promoting prostate cancer cell proliferation
      through activation of p70 S6 kinase and up-regulation of cyclin D1.
AB  - Both androgen and phosphatidylinositol 3-kinase (PI3K) signaling are critical for
      cell proliferation of androgen receptor (AR)-positive prostate cancer cells, but
      the underlying mechanisms are still not fully understood. Here we report that
      serum- and glucocorticoid-inducible kinase 3 (SGK3), a Ser/Thr kinase functioning
      downstream of PI3K, is an AR transcriptional target and promotes prostate cancer
      cell proliferation. SGK3 expression is up-regulated by androgen DHT via AR. We
      identified an AR-binding region at the sgk3 locus, which confers androgen
      responsiveness of sgk3 promoters. Interestingly, we found that androgen/AR
      dependent SGK3 expression requires estrogen receptor (ER) (including both
      isoforms, ERalpha and ERbeta). Depletion of ER blocked DHT-induced SGK3
      expression. Functionally, knockdown of SGK3 expression significantly decreased
      LNCaP prostate cancer cell proliferation by inhibiting G1 to S phase cell cycle
      progression. We further provided evidence that SGK3 promotes p70 S6 kinase
      (p70S6K) activation and increases cyclin D1 levels. In summary, our study
      identifies SGK3 as an AR target and provides a novel androgen-induced cell
      proliferation mechanism mediated by the AR-SGK3-p70S6K-cyclin D1 pathway in
      prostate cancer cells.

PMID- 24739043
TI  - Neo-sex chromosome inheritance across species in Silene hybrids.
AB  - Neo-sex chromosomes, which form through the major restructuring of ancestral sex
      chromosome systems, have evolved in various taxa. Such restructuring often
      consists of the fusion of an autosome to an existing sex chromosome, resulting in
      novel sex chromosome formations (e.g. X1X2Y or XY1Y2.). Comparative studies are
      often made between restructured sex chromosome systems of closely related
      species, and here we evaluate the consequences of variable sex chromosome systems
      to hybrids. If neo-sex chromosomes are improperly inherited across species, this
      could lead to aberrant development and reproductive isolation. In this study, we
      examine the fate of neo-sex chromosomes in hybrids of the flowering plants Silene
      diclinis and Silene latifolia. Silene diclinis has a neo-sex chromosome system
      (XY1Y2) that is thought to have evolved from an ancestral XY system that is still
      present in S. latifolia. These species do not hybridize naturally, and improper
      sex chromosome inheritance could contribute to reproductive isolation. We
      investigated whether this major restructuring of sex chromosomes prevents their
      proper inheritance in a variety of hybrid crosses, including some F2 - and later
      generation hybrids, with sex chromosome-linked, species-specific, polymorphic
      markers and chromosome squashes. We discovered that despite the differences in
      sex chromosomes that exist between these two species, proper segregation had
      occurred in hybrids that made it to flowering, including later-generation
      hybrids, indicating that neo-sex chromosome formation alone does not result in
      complete reproductive isolation between these two species. Additionally, hybrids
      with aberrant sex expression (e.g. neuter, hermaphrodite) also inherited the
      restructured sex chromosomes properly, highlighting that issues with sexual
      development in hybrids can be caused by intrinsic genetic incompatibility rather
      than improper sex chromosome inheritance. 

PMID- 24739042
TI  - Inflammatory cytokines in pulmonary hypertension.
AB  - Pulmonary hypertension is an "umbrella term" used for a spectrum of entities
      resulting in an elevation of the pulmonary arterial pressure. Clinical symptoms
      include dyspnea and fatigue which in the absence of adequate therapeutic
      intervention may lead to progressive right heart failure and death. The
      pathogenesis of pulmonary hypertension is characterized by three major processes
      including vasoconstriction, vascular remodeling and microthrombotic events. In
      addition accumulating evidence point to a cytokine driven inflammatory process as
      a major contributor to the development of pulmonary hypertension.This review
      summarizes the latest clinical and experimental developments in inflammation
      associated with pulmonary hypertension with special focus on Interleukin-6, and
      its role in vascular remodeling in pulmonary hypertension. 

PMID- 24739044
TI  - [The role of microRNAs in molecular pathology of esophageal cancer and their
      potential usage in clinical oncology].
AB  - MicroRNAs are an abundant class of noncoding RNAs (approx. 18- 25 nucleotides in
      length) that suppress translation through binding to their target mRNAs,
      eventually leading to mRNAs degradation. Sequences of these endogenous RNA
      molecules are highly conserved, even among unrelated species, indicating their
      involvement in basic bio-logical processes, such as development, differentiation,
      proliferation or apoptosis. MiRNAs also participate on regulation of cancer stem
      cell functioning, immune system and malignant transformation. This review
      provides a comprehensive overview of miRNAs functions in esophageal cancer, their
      roles in key pathogenetic pathways and disease development, as well as their
      potential usage in clinical routine as bio-markers improving dia-gnosis,
      prognosis and prediction of therapeutic response. Through regulation of signaling
      pathways important in malignant transformation, miRNAs present also promising
      therapeutic targets.

PMID- 24739045
TI  - [Lobular breast cancer in man - case report and review of the literature].
AB  - CASE: Herein we report a case of a man with a B- cell non-Hodgkin lymfoma,
      primarily diagnosed by topographic and morfology tokens as lobular breast
      carcinoma and, as such, it was treated by chemotherapy and endocrine therapy. The
      treatment resulted in complete remission for 3,5 years. However, the subsequent
      relapses that arised in retrocrural and left axilary area did not respond
      adequately to breast cancer targeted chemotherapy. Therefore the patient
      underwent re-exstirpation of axillary lymph node yielding a surprising histology
      finding of folicular lymphoma. The primary biopsy specimen was histologicaly
      reevaluated and the initial dia-gnosis was reclassified as folicular lymphoma.
      The patient was given an adequate chemotherapy and targeted treatment that
      established a complete remission. Six months afterwards there was a relapse
      detected in the retrocrural area. The patient underwent palliative radiotherapy
      that brought about complete remission and, so far, he is in good condition. It
      has been eight years since the cancer dia-gnosis was established. This case
      report is appended by review of literature dealing with diagnostic confusion of
      these two malignancies. CONCLUSION: Re -biopsy plays a significant role in case
      of treatment strategy controversies, predominantly on condition of atypical
      course of malignant disease. It should always be considered in case of cancer
      relapse, especially if the phenotype specfication could affect the treatment
      decision.

PMID- 24739046
TI  - [Psychoneuroimmunology in context of comprehensive breast cancer treatment].
AB  - BACKGROUND: Numerous studies have proven a relationship between stress and cancer
      progression or recurrence, and on the other hand, positive effects of
      psychological and social support and interventions on cancer patients quality of
      life. PURPOSE: This review article aims to provide an overview of recent studies
      that dealt with effects of psychosocial interventions on health and psychological
      state of breast cancer patients, from cellular and immune response over coping
      skills to overall survival. CONCLUSION: Both short- and long-term studies have
      proven positive effects of psychosocial interventions on levels of stress
      hormones, cellular (immune) response and general patients quality of life. On the
      other hand, findings on overall survival are contradictory and cannot provide
      unambiguous conclusions.

PMID- 24739047
TI  - Wage -specific assessment of mammography screening in Brazilian women.
AB  - OBJECTIVE: Mammography is an inexpensive examination that has become a standard
      screening method thanks to its cost-effectiveness. Due to an enormous cost
      escalation of cancer treatment over the last years, the assessment of this
      method, especially in the settings of an emerging country, is a matter of serious
      concern. METHODS: A search within the national health database was conducted
      registering the data with nation- wide coverage. Data collection and analysis was
      commenced in 2010 with referrence to the year 2008 as the most recently updated
      period. The obtained information on mammography screening among Brazilian women
      was evaluated by subdividing the data in four groups according to socioeconomic
      status of the subjects. The study population was estimated to comprise about 2
      million individuals. RESULTS: More than 45% of Brazilian women older than 40
      years of age have never undergone a mammography. The figures correlated with the
      income level, reaching an astonishing number of 62.2% in a group of patients with
      the lowest income level. CONCLUSION: Mammography has proved effective in early
      detection of breast cancer in women. This study suggests that the lack of
      compliance in breast cancer screening in Brazil, pronounced especially in low-
      income families, may contribute to the increasing mortality rates associated with
      the disease.

PMID- 24739048
TI  - [Anakinra treatment in Schnitzler syndrome -  results of the first retrospective
      multicenter study in six patients from the Czech Republic].
AB  - BACKGROUND: Schnitzler syndrome is a very rare, acquired, autoinflammatory
      disease of mostly adult onset with characteristic combination of chronic
      recurrent urticaria and monoclonal immunoglobulin M or G gammopathy predisposing
      the patients to malignant lymphoproliferation. In this work, we analyzed the
      results of bio-logical therapy with anakinra on a national level aiming to supply
      data for effective pharmaco-economic estimates, lay the grounds of nationwide
      patient registry, raise awareness among professional public and optimize provided
      health care. PATIENTS AND METHODS: The retrospective study (10/ 2006- 9/ 2013)
      included six males with definite Schnitzler syndrome verified by the new
      Strasbourg criteria. All patients were pretreated with antihistamines,
      nonsteroidal antiinflammatory drugs and glucocorticoids. Four patients underwent
      two or more treatment lines including intravenous bisphosphonates, 2-
      chlorodeoxyadenosine (cladribine), interferonalpha, PUVA photochemotherapy,
      cyclosporine A, thalidomide, bortezomib, chlorambucil, cyclophosphamide,
      colchicine and methotrexate. Anakinra monotherapy was initiated in standard
      dosing (100 mg subcutaneously daily). RESULTS: Complete and partial remissions
      were achieved in five (83%) and one patients (17%), respectively. Complete
      remission was characterized by urticaria and pain regression (within hours),
      normalization of inflammatory markers (with--in days) and bone metabolism
      improvement assessed by the markers of osteoblastic osteoformation and
      osteoclastic osteoresorption in one case (within weeks). With normalized
      inflammatory markers (including interleukin6 and interleukin18), arthralgia and
      sporadic exacerbations of urticaria and fevers persist in the patient in partial
      remission with proven Q703K polymorphism in NLRP3 gene. The median treatment
      followup was 30.5 months (37.2 +/- 31.2 (n = 6)). The dosing interval was
      prolonged in one case of complete remission to 48 hours. No serious adverse
      reactions occurred during anakinra application. CONCLUSION: In Schnitzler
      syndrome, anakinra represents an effective, verified and safe medication with
      potentionally longterm administration not compromising its original efficacy and
      subjective tolerance. Anakinra, blocking autonomous inflammatory reaction of the
      organism via interleukin1 pathway, is a generally accepted first line treatment
      that should be made available in standard dosing for all Schnitzler patients.

PMID- 24739049
TI  - [On the importance of standardization in the assessment of population-based
      cancer patient survival in the Czech Republic -  methodology and results from the
      Czech National Cancer Registry].
AB  - BACKGROUND: Calculating 5-year overall and relative survival is the standard
      method for population-based analyses in oncology. Survival rates based on
      population data do not, however, guarantee standardized benchmarks for comparison
      of different patient populations, which is especially true when compared
      populations differ considerably in age structure and representation of clinical
      stages. In this paper, we present and compare statistical methods for
      standardization of cancer survival rates. PATIENTS AND METHODS: Using data of the
      Czech National Cancer Registry, we estimated 5-year overall and relative survival
      estimates for periods 2001- 2005 and 2006- 2010. To demonstrate the effect of
      standardization, we calculated crude and age -standardized survival rates as well
      as survival rates standardized for both age and clinical stage. RESULTS: Our
      results show that the particular standardization method influences resulting 5
      year overall and relative survival rates regarding both within and between time
      periods comparisons. In addition, our results document a recent improvement in 5
      year relative survival between periods 2001- 2005 and 2006- 2010 for 19 of 20
      evaluated diagnoses. All most prevalent cancers including prostate, lung,
      colorectal, breast, kidney, and uterine cancer and melanoma were observed among
      the diagnoses with statistically significantly improved patient survival.
      CONCLUSION: Unless the use of standardization to the age and stage of tumor is
      limited due to a small number of patients in individual age-  and stage- specific
      subgroups, this method can be considered as a proper statistical methodology for
      the population assessment of Czech cancer patient survival rates.

PMID- 24739050
TI  - Adenocarcinoma of the rete testis - a rare case of testicular malignancy.
AB  - BACKGROUND: Adenocarcinoma of rete testis is an extremely rare dia-gnosis
      described in around 70 patients worldwide. The prognosis of the disease in
      metastatic stage is very poor and there is no standard systemic treatment
      available. CASE: Herein we present a unique case report of a 47-year- old man
      with metastatic adenocarcinoma of rete testis who achieved substantial disease
      response after four cycles of paclitaxel, ifosfamide and cisplatin. The
      chemotherapy was administered in five -day regimen, which comprised 250 mg/ m2 of
      paclitaxel on day one, 20 mg/ m2 of cisplatin on day one to five and 1,2 g/ m2 of
      ifosfamide on day one to five, in a three-week interval. The patient received
      prophylactic pegfilgrastim after each cycle of TIP. The treatment was well
      tolerated -  without any significant toxicity. RESULT: Patient achieved a partial
      14- month remission. CONCLUSION: On basis of this experience we suggest that
      paclitaxel, ifosfamide and cisplatin might be adopted as novel agents in
      treatment of rete testis adenocarcinoma.

PMID- 24739051
TI  - Renal oncocytoma with invasive histopathologic features -  case report.
AB  - BACKGROUND: Renal oncocytoma is an uncommon tumor, classified as a benign renal
      neoplasm in the World Health Organisation classification of renal tumours.
      Despite it there were described several reports with invasive histopathologic
      features. CASE REPORT: We describe a case of renal oncocytoma with bizzare cells
      and invasion of renal sinus fat tissue. We performed immunohistochemical analysis
      of the case and a review of relevant literature. CONCLUSION: In order to set up
      the right dia-gnosis the perfect co- operation of clinicians and pathologists is
      necessary. In our opinion, in accordance with other authors, the renal
      oncocytomas should be considered as having a very low rather than no malignant
      potential, in spite of clinically benign behavior, supplementing a hypothesis,
      whether renal oncocytomas may be considered as a precancerous lesion of
      chromophobe carcinoma.

PMID- 24739052
TI  - [Continuing progress in withdrawal of axillary dissection in early stage breast
      cancer].
AB  - For a long period of time, axillary dissection represented a standard approach
      for axillary node management in the case of sentinel node biopsy positivity
      during early stage breast cancer treatment. In recent years, there has been a
      trend to highlight the morbidity of such an axillary procedure considering
      longterm survival of early stage breast cancer patients. Two big trials, AMAROS
      and Z0011, were initiated to answer the question whether axillary dissection
      should be performed in the case of positivity of axillary sentinel node
      considering the fact that more than 70% of these patients will have no metastasis
      found during the axillary dissection and such a procedure only increases the
      morbidity of the surgery. Considering the results of the above mentioned trials,
      axillary dissection may be avoided in the case of fulfilling of inclusion
      criteria of these trials without any impact on the patient survival. IBCSG 23- 01
      study brought similar conclusion in the case of micrometastasis in axillary
      sentinel node.

PMID- 24739053
TI  - Theoretical study of the binding energy of a methane molecule in a (H2O)20
      dodecahedral cage.
AB  - The interaction energy of a methane molecule encapsulated in a dodecahedral water
      cage is calculated using the MP2, MP2C, various dispersion-corrected DFT, and
      diffusion Monte Carlo (DMC) methods. The MP2, MP2C, and DMC methods give binding
      energies of -5.04, -4.60, and -5.3 +/- 0.5 kcal/mol, respectively. In addition,
      the two- and three-body contributions are evaluated using the DFT, MP2, and
      CCSD(T) methods. All of the DFT methods considered appreciably overestimate the
      magnitude of the three-body contribution to the interaction energy. The two- and
      three-body energies are further analyzed by use of symmetry-adapted perturbation
      theory (SAPT) which allows decomposition into electrostatics, exchange,
      induction, and dispersion contributions. The SAPT calculations reveal that the
      induction, dispersion, and exchange three-body contributions to the methane-cage
      binding energy are all sizable, with the net three-body contribution to the
      binding energy being about 1 kcal/mol. 

PMID- 24739054
TI  - Hyperimmunoglobulin E syndrome presenting as eosinophilic pustular folliculitis:
      a case report.

PMID- 24739055
TI  - Toll-like receptor-4 signalling in the progression of non-alcoholic fatty liver
      disease induced by high-fat and high-fructose diet in mice.
AB  - The aim of the present study was to investigate Toll-like receptor-4 (TLR4)
      signalling at different stages of non-alcoholic fatty liver disease (NAFLD)
      induced by a high-fat, high-fructose (HFHFr) diet in mice. Both TLR4 wild-type
      (WT) and mutant (TLR4(mut) ) mice were fed either standard chow (SC) or the HFHFr
      diet for different periods of time from 4 to 16 weeks. Pathological
      characteristics and function of the liver were assessed. Simple steatosis,
      steatohepatitis and hepatic fibrosis occurred sequentially in Week 4, 8 and 16 in
      WT mice fed with the HFHFr. Expression of TLR4, myeloid differentiation factor 88
      (MyD88), interferon regulatory factor (IRF) 3 and IRF7 started to increase at
      Week 4, peaked at Week 8 and then declined to basal levels at Week 16. This
      pattern was consistent with changes in inflammation in the liver revealed by
      haematoxylin and eosin staining. However, lipid accumulation, inflammation and
      fibrosis in livers of TLR4(mut) mice fed the HFHFr diet were significantly
      alleviated. In addition, the expression of activin A in WT mice fed the HFHFr
      diet increased at Week 16. The data suggest that TLR4 signalling mediates non
      alcoholic steatohepatitis before fibrosis and that activin A is subsequently
      involved in NAFLD.

PMID- 24739056
TI  - The multiple sclerosis intimacy and sexuality questionnaire-19: reliability,
      validity, and factor structure of the Persian version.
AB  - INTRODUCTION: The Multiple Sclerosis Intimacy and Sexuality Questionnaire-19
      (MSISQ-19) was designed to assess the perceived influence of multiple sclerosis
      (MS) symptoms on sexual activity and satisfaction. AIMS: This study aimed to
      translate and validate the MSISQ-19 in women with MS in Iran. METHODS: The
      translation of the original questionnaire was carried out in accordance with a
      standard forward-backward procedure. Then, a sample of 226 married women with MS
      completed the questionnaire. Reliability was estimated using Cronbach's alpha
      coefficient. Concurrent validity was assessed by comparison with the Female
      Sexual Function Index (FSFI), the Expanded Disability Status Scale (EDSS), and
      the Beck Depression Inventory-II (BDI-II). The factor structure of the
      questionnaire was extracted by performing exploratory factor analyses. All
      patients underwent a full neurologic examination. MAIN OUTCOME MEASURES: MSISQ-19
      score was the main outcome measure. RESULTS: The mean age of participants was
      35.77 years (SD = 8.07), with mean disease duration of 1.84 years (SD = 0.79).
      Cronbach's alpha coefficient was 0.90 for total MSISQ-19 score, with values of
      0.85, 0.90, and 0.78 for the subscales assessing primary, secondary, and tertiary
      sexual dysfunction, respectively. The principal component analysis indicated a
      three-factor solution, similar to that found in the original validation study,
      that explained 63.0% of the total variance for women with MS. Scores on the MSISQ
      19 and its subscales correlated with scores on the FSFI, EDSS, and BDI-II (all P
      < 0.01). CONCLUSION: In general, the findings suggest that the MSISQ-19 is a
      reliable and valid measure of sexual function among Iranian women with MS.
      However, further studies are needed to establish psychometric properties for male
      MS patients in Iran.

PMID- 24739057
TI  - From the lymph nodes to the muscles: an unusual case of refractory familial
      Mediterranean classic Kaposi sarcoma.

PMID- 24739058
TI  - Ethnic differences in tobacco use during pregnancy: findings from a primary care
      sample in Sao Paulo, Brazil.
AB  - OBJECTIVES: Tobacco use during pregnancy is a global health concern. To date the
      majority of research originates in developed countries, thus we have a need to
      better understand factors related to maternal health in developing countries. We
      examine the prevalence and correlates of smoking by ethnicity in a sample of
      pregnant primary care patients in Sao Paulo, Brazil. DESIGN: Data were obtained
      from completed surveys during perinatal care visits in primary care clinics. We
      examine a sample of 811 pregnant women surveyed during 20-30 weeks of pregnancy.
      Multiple logistic regression was used to obtain odds ratios (OR) and 95%
      confidence intervals (95% CI). RESULTS: We found significant ethnic differences
      in smoking during pregnancy. Compared to White women, Black women were more
      likely to use tobacco during pregnancy (OR: 1.95; 95% CI: 1.16-3.27). In the
      fully adjusted model, when accounting for common mental disorders, differences in
      smoking during pregnancy by ethnicity remained (OR: 1.96; 95% CI: 1.14-3.36).
      CONCLUSIONS: There are ethnic differences in tobacco use during pregnancy.
      Clinical implications including universal screening for tobacco use during
      pregnancy and culturally relevant approaches to smoking cessation are suggested.

PMID- 24739059
TI  - Are glucocorticoids harmful to bone in early rheumatoid arthritis?
AB  - In the past, patients with rheumatoid arthritis (RA) were treated with
      monotherapy with conventional drugs, such as sulfasalazine, methotrexate, and
      intramuscular gold, which often leads to persistent arthritis, loss of functional
      capacity, and decreased quality of life. Both active RA and the use of high-dose
      glucocorticoids (GCs) are associated with generalized bone loss and fractures,
      but it is well known that GCs have a strong immunosuppressive effect. With the
      introduction of tumor necrosis factor (TNF-alpha)-blockers and other biologics,
      clinical remission is a realistic target in approximately half of the early RA
      patients; the same seems to be true for the use of methotrexate with chronic low
      dose or initially high-dose GCs. With the use of a treat-to-target strategy
      focusing on clinical remission or low disease activity in early RA patients, the
      negative effects of systemic inflammation on bone can be arrested, and both local
      bone loss (in the joints) and generalized bone loss at the spine and hips can be
      prevented. 

PMID- 24739060
TI  - Borderline resectable pancreatic adenocarcinoma, is conversion therapy realistic?

PMID- 24739061
TI  - Inter- and intra-fraction geometric errors in daily image-guided radiotherapy of
      free-breathing breast cancer patients measured with continuous portal imaging.
AB  - BACKGROUND: Daily image-guided radiotherapy (IGRT) using two orthogonal setup
      images may be inaccurate for breast cancer patients treated in free breathing
      because the setup images may capture the patient in a breathing phase that is not
      representative of the mean anatomy. The aim of this study was to quantify the
      setup errors in breast radiotherapy after image-guided setup correction based on
      two orthogonal setup images acquired in free breathing. METHODS AND MATERIALS:
      For 16 breast cancer patients with daily image-pair based IGRT, continuous portal
      imaging (7.5 Hz) were acquired at each treatment fraction during the delivery of
      the two tangential fields. For each portal image, the chest wall position
      relative to the planned position was determined in the imager direction
      orthogonal to the cranio-caudal direction. It yielded the time resolved setup
      error in this direction throughout the 16 treatment courses. RESULTS: The mean
      absolute setup error exceeded 5 mm in 0.9% (first field) and 1.8% (last field) of
      the treatments. The group mean error (M) and the standard deviations of the
      random (sigma) and systematic (Sigma) setup errors were M=-0.7 mm, Sigma=1.1 mm,
      sigma=1.5 mm (first field) and M=-0.2 mm, Sigma=1.4 mm, sigma=1.7 mm (last
      field). The negative sign of M indicates that less lung than planned was included
      in the treatment fields. Intra-field peak-to-peak chest wall motion amplitudes
      were patient dependent with patient mean values of 2.0+/-0.7 mm [range 1.1-3.2
      mm]. The largest observed intra-field motion amplitude was 8 mm. CONCLUSION:
      Image-guided setup based on orthogonal planar images acquired in free breathing
      without synchronization with the respiratory phase was found to result in
      accurate tangential breast radiotherapy with only few outliers.

PMID- 24739062
TI  - Conformational changes in human Hsp70 induced by high hydrostatic pressure
      produce oligomers with ATPase activity but without chaperone activity.
AB  - We investigated the folding of the 70 kDa human cytosolic inducible protein
      (Hsp70) in vitro using high hydrostatic pressure as a denaturing agent. We
      followed the structural changes in Hsp70 induced by high hydrostatic pressure
      using tryptophan fluorescence, molecular dynamics, circular dichroism, high
      performance liquid chromatography gel filtration, dynamic light scattering,
      ATPase activity, and chaperone activity. Although monomeric, Hsp70 is very
      sensitive to hydrostatic pressure; after pressure had been removed, the protein
      did not return to its native sate but instead formed oligomeric species that lost
      chaperone activity but retained ATPase activity. 

PMID- 24739063
TI  - Synergistic sporicidal effect of ethanol on a combination of orthophthalaldehyde
      and didecyldimethylammonium chloride.
AB  - The objective of this study was to evaluate the potential synergistic effect of
      ethanol on a combination of orthophthalaldehyde (OPA) and didecyldimethylammonium
      chloride (DDAC) against the spores of Bacillus subtilis var. Niger. The
      quantitative carrier test for sporicidal testing of high-level disinfectants
      according to the guideline of China (Technical Standard for Disinfection 2002)
      was used as method. Considerable synergistic effect was observed after a 30-min
      treatment at 20 degrees C. There was an augment in mean log reduction as the
      concentration of DDAC was increased ranging from 0.2 to 3 g l(-1) in combination
      with 6 g l(-1) OPA. Ten and 20% ethanol in combination with 6 g l(-1) OPA and 2 g
      l(-1) DDAC caused more than a 3-log reduction while either 6 g l(-1) OPA, 2 g l(
      1) DDAC and 20% ethanol alone or a combination of two of the three agents
      produced less than a 1-log reduction. Further, 40-min exposure time of
      combination of OPA, DDAC and 20% ethanol led to greater than a 5-log reduction in
      spores, and no spore growth was observed following 60- and 90-min exposures.
      SIGNIFICANCE AND IMPACT OF THE STUDY: Orthophthalaldehyde (OPA) is very effective
      at concentrations far lower than its recommended in-use concentration of 0.5%
      (w/v) and is equally effective against both the gram-negative and gram-positive
      bacteria. However, it shows lower activity against spores. The synergistic
      sporicidal effect exhibited by ethanol on a combination of OPA and DDAC can be
      considered to enhance sporicidal activity for using in situations of
      sterilization, to reduce in-use concentration of OPA used alone, which may
      minimize its side effect. OPA may be a more satisfactory and the first-choice
      agent to replace glutaraldehyde (GTA) as a high-level disinfectant for medical
      devices.

PMID- 24739064
TI  - Isomerization of Delta5-androstene-3,17-dione into Delta4-androstene-3,17-dione
      catalyzed by human glutathione transferase A3-3: a computational study identifies
      a dual role for glutathione.
AB  - Glutathione transferases (GSTs) are important enzymes in the metabolism of
      electrophilic xenobiotic and endobiotic toxic compounds. In addition, human GST
      A3-3 also catalyzes the double bond isomerization of Delta5-androstene-3,17-dione
      (Delta(5)-AD) and Delta(5)-pregnene-3,20-dione (Delta(5)-PD), which are the
      immediate precursors of testosterone and progesterone. In fact, GST A3-3 is the
      most efficient human enzyme known to exist in the catalysis of these reactions.
      In this work, we have used density functional theory (DFT) calculations to
      propose a refined mechanism for the isomerization of Delta(5)-AD catalyzed by GST
      A3-3. In this mechanism the glutathione (GSH) thiol and Tyr9 catalyze the proton
      transfer from the Delta(5)-AD C4 atom to the Delta(5)-AD C6 atom, with a rate
      limiting activation energy of 15.8 kcal . mol(-1). GSH has a dual function,
      because it is also responsible for stabilizing the negative charge that is formed
      in the O3 atom of the enolate intermediate. The catalytic role of Tyr9 depends on
      significant conformational rearrangements of its side chain. Neither of these
      contributions to catalysis has been observed before. Residues Phe10, Leu111, Ala
      208, and Ala 216 complete the list of the important catalytic residues. The
      mechanism detailed here is based on the GST A3-3:GSH:Delta(4)-AD crystal
      structure and is consistent with all available experimental data.

PMID- 24739065
TI  - Reply to "precipitants of heart failure must be fully considered when predicting
      readmission".

PMID- 24739066
TI  - Early return of continence in patients undergoing robot-assisted laparoscopic
      prostatectomy using modified maximal urethral length preservation technique.
AB  - PURPOSE: To evaluate the impact of maximal urethral length preservation (MULP)
      technique in comparison with posterior urethral reconstruction and anterior
      bladder suspension (PRAS) technique on the continence rates (CR), time to achieve
      continence among patients with prostate cancer (PCa) undergoing robot-assisted
      laparoscopic prostatectomy (RALP). PATIENTS AND METHODS: We prospectively
      analyzed the CR, time to achieve continence, pre- and postoperative prostate
      specific antigen (PSA) levels, rates of positive margins among three groups of
      continent men with PCa undergoing RALP from whom consent was obtained. Each group
      consisted of 30 patients: PRAS was performed in group A, combined MULP and PRAS
      in group B, and MULP in group C. Continence was measured by patient self
      reporting of the number of pads/24 h. RESULTS: No differences were detected in
      the age, preoperative PSA levels, biochemical recurrence, prostate volume, and
      positive margins for the three groups. Men in groups B and C had marked
      improvement in CR 1, 3, and 6 months after catheter removal vs group A (50% and
      70% vs 10%, 90% and 96.66% vs 23.3% and 100%, 100% vs 53.3%, respectively,
      P<0.0001). The average and median times to continence were significantly shorter
      in group B (5.4 and 4 weeks) and C (3.8 and 3 weeks) vs group A (27.4 and 22.5
      weeks), P<0.00001. Using Cox regression analysis, only MULP and MULP+PRAS
      techniques were significantly correlated with continence outcomes 1, 3, and 6
      months after catheter removal. CONCLUSIONS: MULP rather than PRAS confers higher
      postoperative CR and shorter time to achieve continence among patients with PCa
      who underwent RALP without increasing risk of positive margin.

PMID- 24739067
TI  - Conserved residues at the MAPKs binding interfaces that regulate transcriptional
      machinery.
AB  - Signaling through c-Raf downstream pathways is the crucial subject of extensive
      studies because over expressed or mutated genes in this pathway lead to a variety
      of human cancers. On the basis of cellular localization, this pathway has been
      sub-divided into two cascades. The first RAF1-MEK1-ERK2 cascade which remains in
      the cytosol, whereas the second MEK1-ERK2-RSKs transduces into the nucleus and
      regulates the transactivation function. But how a few amino acids critically
      regulate the transcriptional function remains unclear. In this paper, we have
      performed in silico studies to unravel how atomic complexities at the MEK1-ERK2
      RSKs pathways intercedes different functional responses. The secondary structure
      of the ERK, RSKs have been modeled using Jpred3, PSI-PHRED, protein modeler, and
      Integrated sequence analyzer from Discovery Studio software. Peptides of RSKs
      isozymes (RSK1/2/3/4) were built and docked on ERK2 structure using ZDOCK module.
      The hydropathy index for the RSKs molecules was determined using the KYTE
      DOOLITTLE plot. The simulations of complex molecules were carried out using a
      CHARMM force field. The protein-protein interactions (PPIs) in different cascade
      of MAP kinase (MAPK) have been shown to be similar to those predicted in vivo.
      PPIs elucidate that the amino acids located at the conserved domains of MAPK
      pathways are responsible for transactivation functions. 

PMID- 24739068
TI  - Reactions of the unsaturated ditungsten complexes [W2Cp2(MU-PPh2)2(CO)x] (x = 1,
      2) with nitric oxide: stereoselective carbonyl displacement and oxygen-transfer
      reactions of a nitrite ligand.
AB  - The dicarbonyl complex trans-[W2Cp2(MU-PPh2)2(CO)2] (Cp = eta(5)-C5H5) reacted
      rapidly with NO (5% in N2) at 273 K to give selectively cis-[W2Cp2(MU
      PPh2)2(NO)2]. In contrast, the analogous reactions of monocarbonyl [W2Cp2(MU
      PPh2)2(MU-CO)] yielded either trans-[W2Cp2(MU-PPh2)2(NO)2] or the nitrito complex
      [W2Cp2(MU-PPh2)2(ONO)(CO)(NO)] (W-W = 2.9797(4) A), depending on experimental
      conditions, with the latter presumably arising from reaction with trace amounts
      of oxygen in the medium. The stereoselectivity of the above reactions can be
      rationalized by assuming the participation of 33-electron [W2Cp2(MU
      PPh2)2(CO)(NO)] intermediates which rapidly add a second molecule of NO via
      eta(2)-C5H5 intermediates to eventually yield the corresponding dinitrosyls with
      inversion of the stereochemistry at the dimetal center, as supported by density
      functional theory (DFT) calculations. The nitrito complex was thermally unstable
      and evolved through oxygen transfer either to the carbonyl ligand, to yield the
      above dinitrosyls with release of CO2, or to the phosphide ligand, to give the
      phosphinito derivative cis-[W2Cp2(MU-OPPh2)(MU-PPh2)(NO)2], depending on
      experimental conditions. According to DFT calculations, the first process would
      involve transient dissociation/recombination of the nitrite ligand followed by
      coupling to carbonyl to give an intermediate with a chelate W{C,N-C(O)ON(O)}
      ring. Indeed, the nitrite ligand could be easily removed upon reaction of the
      nitrito complex with Na(BAr'4), but immediate decomposition also took place to
      render the electron-precise dicarbonyl [W2Cp2(MU-PPh2)2(CO)2(NO)]BAr'4 (W-W =
      2.9663(3) A) as the unique product (Ar' = 3,5-C6H3(CF3)2). Attempts to
      decarbonylate the latter complex photochemically yielded instead the oxo
      derivatives cis- and trans-[W2Cp2(MU-PPh2)2(O)(NO)]BAr'4 as the only isolable
      products (W-W = 2.980(2) and 3.0077(3) A, respectively). 

PMID- 24739069
TI  - AtHAP5A modulates freezing stress resistance in Arabidopsis through binding to
      CCAAT motif of AtXTH21.
AB  - Several eukaryotic Heme-associated proteins (HAPs) have been reported to bind
      specifically to DNA fragments containing CCAAT-box; however, the physiological
      functions and direct targets of these HAP proteins in plants remain unclear. In
      this study, we showed that AtHAP5A as a transcription factor interacted with
      CCAAT motif in vivo, and AtXTH21, one direct target of AtHAP5A, was involved in
      freezing stress resistance. The AtHAP5A overexpressing plants were more tolerant,
      whereas the loss-of-function mutant of AtHAP5A was more sensitive to freezing
      stress than wild-type plants. Chromatin immunoprecipitation (ChIP) assay
      demonstrated that AtHAP5A could bind to five fragments that contained CCAAT
      motifs in the AtXTH21 promoter. Similarly, the AtXTH21 overexpressing plants
      exhibited improved freezing resistance, while xth21 knockdown mutants displayed
      decreased freezing resistance. Notably, the modulated freezing resistance of
      AtHAP5A overexpressing plants and knockout mutant could be reversed by the xth21
      mutant and AtXTH21 overexpressing plants, respectively, indicating that AtHAP5A
      might act upstream of AtXTH21 in freezing stress. Additionally, modulation of
      AtHAP5A and AtXTH21 expression had the same effects on abscisic acid (ABA)
      sensitivity and reactive oxygen species (ROS) metabolism. Taken together, these
      results demonstrated that AtHAP5A modulates freezing stress resistance in
      Arabidopsis through binding to the CCAAT motif of AtXTH21. 

PMID- 24739070
TI  - A missed opportunity - consequences of unknown levetiracepam pharmacokinetics in
      a peritoneal dialysis patient.
AB  - BACKGROUND: Levetiracetam is a frequently used drug in the therapy of partial
      onset, myoclonic and generalized tonic-clonic seizures. The main route of
      elimination is via the kidneys, which eliminate 66% of the unchanged drug as well
      as 24% as inactive metabolite that stems from enzymatic hydrolysis. Therefore
      dose adjustments are needed in patients with chronic kidney disease stage 5 D,
      i.e. patients undergoing dialysis treatment. In this patient population a dose
      reduction by 50% is recommended, so that patients receive 250-750 mg every 12
      hours. However "dialysis" can be performed in using different modalities and
      treatment intensities. For most of the drugs pharmacokinetic data and dosing
      recommendations for patients undergoing peritoneal dialysis are not available.
      This is the first report on levetiracetam pharmacokinetics in a peritoneal
      dialysis patient. CASE PRESENTATION: A 73-y-old Caucasian male (height: 160 cm,
      weight 93 kg, BMI 36.3 kg/m2) was admitted with a Glasgow Coma Scale of 10. Due
      to diabetic and hypertensive nephropathy he was undergoing peritoneal dialysis
      for two years. Eight weeks prior he was put on levetiracetam 500 mg twice daily
      for suspected partial seizures with secondary generalization. According to the
      patient's wife, levetiracetam lead to fatigue and somnolence leading to trauma
      with fracture of the metatarsal bone. Indeed, even 24 hours after discontinuation
      of levetiracetam blood level was still 29.8 mg/l (therapeutic range: 12 - 46
      mg/l). Fatigue and stupor had disappeared five days after discontinuation of the
      levetiracepam. A single dose pharamockinetic after re-exposure showed an
      increased half life of 18.4 hours (normal half life 7 hours) and levetiracetam
      content in the peritoneal dialysate. Both half-life and dialysate content might
      help to guide dosing in this patient population. CONCLUSION: If levetiracetam is
      used in peritoneal dialysis patients it should be regularly monitored to avoid
      supratherapeutic levels that could lead to severe sequelae.

PMID- 24739071
TI  - Boolean logic tree of graphene-based chemical system for molecular computation
      and intelligent molecular search query.
AB  - The most serious, and yet unsolved, problem of constructing molecular computing
      devices consists in connecting all of these molecular events into a usable
      device. This report demonstrates the use of Boolean logic tree for analyzing the
      chemical event network based on graphene, organic dye, thrombin aptamer, and
      Fenton reaction, organizing and connecting these basic chemical events. And this
      chemical event network can be utilized to implement fluorescent combinatorial
      logic (including basic logic gates and complex integrated logic circuits) and
      fuzzy logic computing. On the basis of the Boolean logic tree analysis and logic
      computing, these basic chemical events can be considered as programmable "words"
      and chemical interactions as "syntax" logic rules to construct molecular search
      engine for performing intelligent molecular search query. Our approach is helpful
      in developing the advanced logic program based on molecules for application in
      biosensing, nanotechnology, and drug delivery. 

PMID- 24739072
TI  - Effectiveness of peroral endoscopic myotomy in the treatment of achalasia: a
      pilot trial in Chinese Han population with a minimum of one-year follow-up.
AB  - OBJECTIVE: To investigate the outcomes of Chinese Han patients who underwent
      peroral endoscopic myotomy (POEM) for achalasia. METHODS: Patients undergoing
      POEM for achalasia at the Affiliated Drum Tower Hospital of Nanjing University
      Medical School were prospectively enrolled in this study, with a follow-up
      duration of at least one year. Their outcomes were evaluated by analyzing
      esophageal manometry, timed barium esophagogram and 36-Item Short Form Health
      Survey (SF-36), which were performed before surgery, 5 days after surgery and at
      the last follow-up. Patients' symptom relief was considered the primary outcome.
      Secondary outcomes included lower esophageal sphincter (LES) pressure, esophageal
      emptying, patients' quality of life (QoL) and procedure-related complications.
      RESULTS: Eighty-seven patients were included in the study. Eckardt score after
      POEM was remarkably lower than the preoperative score (0.4 +/- 0.7 vs 7.1 +/-
      2.1, P = 0.001). The preoperative LES pressure was 32.4 +/- 15.3 mmHg, which was
      decreased to 3.8 +/- 3.9 mmHg immediately after surgery. The height of the barium
      column at 1 min after barium swallow was significantly reduced after treatment
      (11.7 +/- 1.2 cm vs 3.2 +/- 1.6 cm, P < 0.001). The patients' QoL was also
      improved, as indicated by obviously increased physical and mental component
      summary (PCS and MCS) scores of the SF-36. Complications occurred during POEM
      included cutaneous emphysema, mucosal injury and pneumothorax. CONCLUSION: POEM
      is an effective approach for treating achalasia, which can relieve the symptoms
      of achalasia by improving esophageal emptying and lowering LES pressure.

PMID- 24739073
TI  - Effect of chlorthalidone, amlodipine, and lisinopril on visit-to-visit
      variability of blood pressure: results from the Antihypertensive and Lipid
      Lowering Treatment to Prevent Heart Attack Trial.
AB  - Few randomized trials have compared visit-to-visit variability (VVV) of systolic
      blood pressure (SBP) across drug classes. The authors compared VVV of SBP among
      24,004 participants randomized to chlorthalidone, amlodipine, or lisinopril in
      the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial
      (ALLHAT). VVV of SBP was calculated across 5 to 7 visits occurring 6 to 28 months
      following randomization. The standard deviation (SD) of SBP was 10.6 (SD=5.0),
      10.5 (SD=4.9), and 12.2 (SD=5.8) for participants randomized to chlorthalidone,
      amlodipine, and lisinopril, respectively. After multivariable adjustment
      including mean SBP across visits and compared with participants randomized to
      chlorthalidone, participants randomized to amlodipine had a 0.36 (standard error
      [SE]: 0.07) lower SD of SBP and participants randomized to lisinopril had a 0.77
      (SE=0.08) higher SD of SBP. Results were consistent using other VVV of SBP
      metrics. These data suggest chlorthalidone and amlodipine are associated with
      lower VVV of SBP than lisinopril.

PMID- 24739074
TI  - Homology modeling of human kynurenine aminotransferase III and observations on
      inhibitor binding using molecular docking.
AB  - Kynurenine aminotransferase (KAT) isozymes are responsible for catalyzing the
      conversion of kynurenine (KYN) to kynurenic acid (KYNA), which is considered to
      play a key role in central nervous system (CNS) disorders, including
      schizophrenia. The levels of KYNA in the postmortem prefrontal cortex and in the
      Cerebrospinal fluid (CSF) of schizophrenics are greater than normal brain. A
      basic strategy to decrease kynurenic acid levels is to promote the inhibition of
      the biosynthetic KAT isozymes. As there is no crystallographic model for human
      kynurenine aminotransferase III (KAT III), therefore, homology modeling has been
      performed based on the Mus musculus kynurenine aminotransferase III crystal
      structure (PDB ID: 3E2Y) as a template, and the model of the human KAT III was
      refined and optimized with molecular dynamics simulations. Further evaluation of
      the model quality was accomplished by investigating the interaction of KAT III
      inhibitors with the modeled enzyme. Such interactions were determined employing
      the AutoDock 4.2 program using the MGLTools 1.5.6 package. The most important
      interactions for the binding of the inhibitors, which are probably also central
      components of the active site of KAT III, were identified as Ala134, Tyr135, Lys
      280, Lys 288, Thr285 and Arg429, which provide hydrogen bond interactions.
      Additionally, Tyr135 and Arg429 have good electrostatic interactions with
      inhibitors consistent with these residues also being essential for inhibition of
      the enzyme activity. We expect that this model and these docking data will be a
      useful resource for the rational design of novel drugs for treating
      neuropathologies. 

PMID- 24739075
TI  - Protective effects of influenza A (H1N1) pandemic 2009 vaccination against the
      onset of influenza-like illness and asthma exacerbation in Japanese children.
AB  - BACKGROUND: Vaccination against influenza A(H1N1)pdm09 in Japan started in
      October 2009. Children with asthma are considered as a high-risk group and are
      recommended to preferentially receive the vaccine. OBJECTIVE: To identify the
      clinical effects of vaccination in Japanese children with and without asthma.
      METHODS: We conducted a cross-sectional, questionnaire-based survey to compare
      vaccination rates, vaccine effectiveness against physician-diagnosed influenza A
      infection (PDIA), and consecutive asthma exacerbations between children with and
      without asthma. RESULTS: Of the 460 children included in this study, those with
      asthma had higher vaccination rates (46.5%, 67/144) than those without asthma
      (30.4%, 96/316). Influenza A infections were diagnosed in 28 of 163 vaccinated
      children (17.2%) compared to 164 of 297 unvaccinated children (55.2%, p < 0.001).
      Comparison of positive influenza diagnosis rates between vaccinated and
      unvaccinated children with and without asthma showed that unvaccinated children
      with asthma had an elevated odds ratio (13.235; 95% confidence interval [CI],
      5.564-32.134) and that treatment for asthma exacerbations was needed in a larger
      proportion of unvaccinated children. Vaccine effectiveness against PDIA was 87%
      (95% CI, 78-93%) overall, 92% (95% CI, 81-96%) in children with asthma and 81%
      (95% CI, 63-91%) in children without asthma, respectively. CONCLUSIONS: The
      administration of an inactivated, split-virus, non-adjuvanted monovalent
      A(H1N1)pdm09 vaccine during the pandemic period reduced the number of physician
      diagnosed influenza A infections and asthma exacerbations in children with
      asthma. Therefore, we strongly recommend that high-risk children with a history
      of asthma receive vaccines during pandemics.

PMID- 24739076
TI  - Occult tinea pedis in an Israeli population and predisposing factors for the
      acquisition of the disease.
AB  - BACKGROUND: Tinea pedis is a commonly encountered dermatophytic infection with a
      clinical prevalence of 15-25%. Limited studies have evaluated the prevalence of
      occult tinea pedis. OBJECTIVES: The aims of this study were to evaluate the
      prevalence of occult tinea pedis in asymptomatic subjects with feet that appeared
      healthy and to identify possible related risk factors. METHODS: A prospective
      study of 221 asymptomatic subjects with apparently normal feet was conducted. All
      subjects completed a questionnaire covering anamnestic details (personal and
      family histories of tinea pedis, preferred footwear) and were examined for foot
      odor and the clinical presence of tinea pedis and onychomycosis. Samples were
      taken from the foot for direct microscopic examination and culture. RESULTS:
      Among the 221 patients, 31 (14.0%) were positive for occult tinea pedis. Positive
      cultures from both the anterior and posterior aspects of the foot were obtained
      in 22 patients. The most common pathogen isolated was Trichophyton rubrum. Strong
      correlations emerged between occult tinea pedis and characteristics such as male
      gender, foot odor, previous personal and family histories of tinea pedis, and
      clinical and mycological evidence of onychomycosis. No significant associations
      were found between occult tinea pedis and age or preferred footwear. CONCLUSIONS:
      The prevalence of occult tinea pedis is similar to that of clinical tinea pedis.
      This may imply that patients with subclinical infection carry a risk for
      transmitting disease similar to that of clinical carriers. This is of great
      importance in the prevention and management of the disease as high-risk
      asymptomatic carriers can be identified.

PMID- 24739077
TI  - Complex self-assembly of reverse poly(butylene oxide)-poly(ethylene oxide)
      poly(butylene oxide) triblock copolymers with long hydrophobic and extremely
      lengthy hydrophilic blocks.
AB  - Amphiphilic block copolymers have emerged during last years as a fascinating
      substrate material to develop micellar nanocontainers able to solubilize,
      protect, transport, and release under external or internal stimuli different
      classes of cargos to diseased cells or tissues. However, this class of materials
      can also induce biologically relevant actions, which complement the therapeutic
      activity of their cargo molecules through their mutual interactions with
      biologically relevant entities (cellular membranes, proteins, organelles...);
      these interactions at the same time, are regulated by the nature, conformation,
      and state of the copolymeric chains. For these reasons, in this paper we
      investigated the self-assembly process and physico-chemcial properties of two
      reverse triblock poly(butylene oxide)-poly(ethylene oxide)-poly(butylene oxide)
      block copolymers, BO14EO378BO14 and BO21EO385BO21, which have been recently found
      to be very useful as drug delivery nanovehicles and biological response modifiers
      under certain conditions (A. Cambon et al. Int. J. Pharm. 2013, 445, 47-57) in
      order to obtain a clear picture of the solution behavior of this class or block
      copolymers and to understand their biological activity. These block copolymers
      are characterized by possessing long BO blocks and extremely lengthy central EO
      ones, which provide them with a rich rheological behavior characterized by the
      formation of flowerlike micelles with sizes ranging from 20 to 40 nm in aqueous
      solution and the presence of intermicellar bridging even at low copolymers
      concentrations as denoted by atomic force microscopy. Bridging is also clearly
      observed by analyzing the rheological response of these block copolymers both
      storage and loss moduli upon changes on time, temperature, and or concentration.
      Strikingly, the relatively wide Poisson distribution of the polymeric chains make
      the present copolymers behave rather distinctly to conventional associative
      thickeners. The observed rich rheological behavior and their tunability also make
      these copolymers promising materials to configure drug gelling depots. 

PMID- 24739078
TI  - Stable isotope evidence for the Bottom Convective Layer homogeneity in the Black
      Sea.
AB  - The Black Sea is the largest euxinic basin on the Earth. The anoxic zone consists
      of the upper part water mass stratified by density, and the lower water mass
      homogenized relative to density (depth >1750 m), named the Bottom Convective
      Layer. To assess homogeneity and possible exchange of matter across the upper and
      lower boundaries of the Bottom Convective Layer, new data on stable isotope
      composition of S, O and H were obtained. Samples were collected in August 2008
      and March 2009 from two stations located in the eastern central part of the Black
      Sea. Distribution of delta(18)O and deltaD values of water for the entire water
      column did not vary seasonally. Appreciable differences were marked for deltaD
      value variation in the picnocline area (water depth 200-400 m) and in the BCL 5 m
      above the bottom that might be caused by penetration of intrusions with elevated
      portion of shelf modified Mediterranean Water. Observed linear relationship
      between delta(18)O (or deltaD) and salinity indicates that mixing water and salt
      occurs at the same time, and the deep water of the Black Sea has two end members:
      the high-salinity Mediterranean seawater and freshwater input. In the Bottom
      Convective Layer, the average delta(34)S (H2S) was -40.6 +/- 0.50/00 and did not
      vary seasonally. At the bottom (depth > 2000 m), (34)S depletion down to 
      41.00/00 was observed. Our delta(34)S (SO4) data are by 2-30/00 higher than those
      measured previously for the Bottom Convective Layer. Sulfate from the aerobic
      zone with delta(34)S (SO4) = +210/00 corresponds to ocean water sulfate and that
      has not been subjected to sulfate reduction. Average delta(34)S (SO4) values for
      depths > 1250 m were found to be +23.0 +/- 0.20/00 (1sigma). Sulfur isotope
      composition of sulfate does not change in the Bottom Convective Layer and on its
      upper and lower boundaries, and does not depend on the season of observation. 

PMID- 24739079
TI  - Assessment of human baroreflex function using carotid ultrasonography: what have
      we learnt?
AB  - The arterial baroreflex is critical to both short- and long-term regulation of
      blood pressure. However, human baroreflex research has been largely limited to
      the association between blood pressure and cardiac period (or heart rate) or
      indices of vascular sympathetic function. Over the past decade, emerging
      techniques based on carotid ultrasound imaging have allowed new means of
      understanding and measuring the baroreflex. In this review, we describe the
      assessment of the mechanical and neural components of the baroreflex through the
      use of carotid ultrasound imaging. The mechanical component refers to the change
      in carotid artery diameter in response to changes in arterial pressure, and the
      neural component refers to the change in R-R interval (cardiac baroreflex) or
      muscle sympathetic nerve activity (sympathetic baroreflex) in response to this
      barosensory vessel stretch. The key analytical concepts and techniques are
      discussed, with a focus on the assessment of baroreflex sensitivity via the
      modified Oxford method. We illustrate how the application of carotid ultrasound
      imaging has contributed to a greater understanding of baroreflex physiology in
      humans, covering topics such as ageing and diurnal variation, and physiological
      challenges including exercise, postural changes and mental stress. 

PMID- 24739080
TI  - Floral biology of two Vanilloideae (Orchidaceae) primarily adapted to pollination
      by euglossine bees.
AB  - Vanilloideae comprises 15 genera distributed worldwide, among which are Vanilla
      and Epistephium (tribe Vanilleae). Based on field and laboratory investigations,
      the pollination biology of V. dubia and E. sclerophyllum was analysed. The former
      was surveyed in a semi-deciduous mesophytic forest at the biological reserve of
      Serra do Japi and in a marshy forest at the city of Pradopolis, southeastern
      Brazil. The latter was examined in rocky outcrop vegetation in the Chapada
      Diamantina, northeastern Brazil. In the studied populations, the tubular flowers
      of V. dubia and E. sclerophyllum were pollinated by bees. Pollen was deposited on
      either their scutellum (V. dubia) or scutum (E. sclerophyllum). The mentum region
      of V. dubia is dry, whereas that of E. sclerophyllum presents a small quantity of
      dilute nectar. Flowers of E. sclerophyllum are scentless, while those of V. dubia
      are odoriferous. Although V. dubia is self-compatible, it needs a pollinator to
      produce fruit. In contrast, E. sclerophyllum sets fruit through spontaneous self
      pollination, but biotic pollination also occurs. Both species are primarily
      adapted to pollination by euglossine bees. Pollination by Euglossina seems to
      have occurred at least twice during the evolution of Vanilleae. Furthermore,
      shifts between rewarding and reward-free flowers and between autogamous and
      allogamous species have been reported among vanillas. 

PMID- 24739081
TI  - Playing smart vs. playing safe: the joint expression of phenotypic plasticity and
      potential bet hedging across and within thermal environments.
AB  - Adaptive phenotypic plasticity evolves when cues reliably predict fitness
      consequences of life-history decisions, whereas bet hedging evolves when
      environments are unpredictable. These modes of response should be jointly
      expressed, because environmental variance is composed of both predictable and
      unpredictable components. However, little attention has been paid to the joint
      expression of plasticity and bet hedging. Here, I examine the simultaneous
      expression of plasticity in germination rate and two potential bet-hedging traits
      - germination fraction and within-season diversification in timing of germination
      - in seeds from multiple seed families of five geographically distant populations
      of Lobelia inflata (L.) subjected to a thermal gradient. Populations differ in
      germination plasticity to temperature, in total germination fraction and in the
      expression of potential diversification in the timing of germination. The
      observation of a negative partial correlation between the expression of
      plasticity and germination variance (potential diversification), and a positive
      correlation between plasticity and germination fraction is suggestive of a trade
      off between modes of response to environmental variance. If the observed
      correlations are indicative of those between adaptive plasticity and bet hedging,
      we expect an optimal balance to exist and differ among populations. I discuss the
      challenges involved in testing whether the balance between plasticity and bet
      hedging depends on the relative predictability of environmental variance. 

PMID- 24739082
TI  - Enhanced hypoglycemic effect of biotin-modified liposomes loading insulin: effect
      of formulation variables, intracellular trafficking, and cytotoxicity.
AB  - Peroral protein/peptide delivery has been one of the most challenging, but
      encouraging topics in pharmaceutics. This article was intended to explore the
      potential of biotin-modified liposomes (BLPs) as oral insulin delivery carriers.
      By incorporating biotin-DSPE into the lipid bilayer, we prepared BLPs using
      reverse evaporation/sonication method. We investigated hypoglycemic effects in
      normal rats after oral administration of BLPs, and the possible absorption
      mechanism by a series of in vitro tests. The relative pharmacological
      bioavailability of BLPs was up to 11.04% that was as much as 5.28 folds of
      conventional liposomes (CLPs). The results showed that the enhanced oral
      absorption of insulin mainly attributed to biotin ligand-mediated endocytosis.
      The results provided proof of BLPs as effective carriers for oral insulin
      delivery. 

PMID- 24739083
TI  - Ice skating promotes postural control in children.
AB  - High fall rates causing injury and enormous financial costs are reported for
      children. However, only few studies investigated the effects of balance training
      in children and these studies did not find enhanced balance performance in
      postural (transfer) tests. Consequently, it was previously speculated that
      classical balance training might not be stimulating enough for children to
      adequately perform these exercises. Therefore, the aim of this study is to
      evaluate the influence of ice skating as an alternative form of balance training.
      Volunteers of an intervention (n = 17; INT: 13.1 +/- 0.4 years) and a control
      group (n = 13; CON: 13.2 +/- 0.3 years) were tested before and after training in
      static and dynamic postural transfer tests. INT participated in eight sessions of
      ice skating during education lessons, whereas CON participated in normal physical
      education. Enhanced balance performance was observed in INT but not in CON when
      tested on an unstable free-swinging platform (P < 0.05) or when performing a
      functional reach test (P < 0.001). This is the first study showing significantly
      enhanced balance performance after ice skating in children. More importantly,
      participating children improved static and dynamic balance control in postural
      tasks that were not part of the training. 

PMID- 24739084
TI  - Computational study of the kinetics and mechanisms for the HCO + O3 reaction.
AB  - The mechanisms of radical-molecule reactions between HCO (formyl radical) and O3
      (ozone) have been investigated by using BH&HLYP and QCISD methods with the 6
      311++G(3df,2p) basis set. The energetics have been refined with CCSD(T) and
      QCISD(T) theoretical approaches with the same basis set based on the geometries
      calculated at the QCISD method. The intermediates of hydrogen-bonded complexes
      and the critical transition states are also examined with the multireference
      methods. Two possible reaction pathways containing hydrogen-abstraction and
      association-elimination processes for the interaction of HCO with O3 are
      proposed. Both reaction mechanisms can occur via the prereactive hydrogen-bonded
      complex, O3-HCO, with 2.45 kcal/mol stability at the CCSD(T) approach with
      respect to the reactants; even so, the hydrogen-abstraction mechanism exhibits a
      lower energy barrier. The rate constants for both processes are also predicted.
      The total rate constant at 298 K is calculated to be in close agreement with the
      experimental value of 8.3 * 10(-13) cm(3) molecule(-1) s(-1). 

PMID- 24739085
TI  - CBCT evaluation of multiple idiopathic internal resorptions in permanent molars:
      case report.
AB  - BACKGROUND: Internal inflammatory root resorption is a rare condition in
      permanent teeth, which requires the presence of necrotic and infected pulp tissue
      within the coronal portion of the root canal system as well as inflamed pulp
      tissue apical to the resorptive defect. The aetiology of internal root resorption
      is not completely understandable, trauma and chronic pulpitis are considered the
      main risk factors. CASE PRESENTATION: We report a rare case of the multiple
      idiopathic resorption in the permanent maxillary and mandibular molars in a
      healthy 33-year-old female patient. In addition to clinical examination the
      patient was imaged using conventional radiography techniques and cone beam
      computed tomography (CBCT).The patient had recurrent throbbing pain in her # 46.
      The radiographic examination including "panoramic radiography and CBCT" revealed
      that radiographic evidence of internal resorption in #37 #36 #35 #34 #33 #47 #46
      #45 #44 #43 #16 #15 #14 #13 and also including in unerupted #17, #26, #27, #28
      teeth. The definitive diagnosis was made with the histopathological examination
      of the extracted tooth. CONCLUSIONS: Internal root resorption is a rare clinical
      process that should be examined using different radiographic modalities. CBCT
      seems to be useful in evaluation of the lesions with superior diagnostic
      performance.

PMID- 24739086
TI  - Comparing temperature effects on Escherichia coli, Salmonella, and Enterococcus
      survival in surface waters.
AB  - The objective of this study was to compare dependency of survival rates on
      temperature for indicator organisms Escherichia coli and Enterococcus and the
      pathogen Salmonella in surface waters. A database of 86 survival datasets from
      peer-reviewed papers on inactivation of E. coli, Salmonella and Enterococcus in
      marine waters and of E. coli and Salmonella in lake waters was assembled. The Q10
      model was used to express temperature effect on survival rates obtained from
      linear sections of semi-logarithmic survival graphs. Available data were
      insufficient to establish differences in survival rates and temperature
      dependencies for marine waters where values of Q10  = 3 and a survival rate of
      0.7 day(-1) could be applied. The Q10 values in lake waters were substantially
      lower in marine waters, and Salmonella inactivation in lake water was, on
      average, twice as fast as E. coli; data on E. coli substantially outnumber data
      on Enterococcus and Salmonella. The relative increase in inactivation with
      increase in temperature is higher in marine waters than lake water, and
      differences in inactivation between Salmonella and E. coli at a given temperature
      were significant in lake water but not in marine waters. SIGNIFICANCE AND IMPACT
      OF THE STUDY: Microbiological quality of surface waters is of paramount
      importance for public health. The novelty of this work is using a large
      compendium of published data to develop the first comparison of temperature
      effects on survival of the pathogen Salmonella and water quality indicator micro
      organisms Escherichia coli and Enterococcus in natural waters. The existing
      relatively large body of knowledge on E. coli survival appears to be useful to
      assess the effect of temperature on survival of Salmonella. Moreover, results of
      this work constitute an essential input in models to support environmental
      management decisions on the use of surface water sources in agriculture,
      aquaculture and recreation.

PMID- 24739087
TI  - Short stature, digit anomalies and dysmorphic facial features are associated with
      the duplication of miR-17 ~ 92 cluster.
AB  - MicroRNAs (miRNAs) are key regulators of gene expression, playing important roles
      in development, homeostasis, and disease. Recent experimental evidence indicates
      that mutation or deregulation of the MIR17HG gene (miR-17 ~ 92 cluster)
      contributes to the pathogenesis of a variety of human diseases, including cancer
      and congenital developmental defects. We report on a 9-year-old boy who presented
      with developmental delay, autism spectrum disorder, short stature, mild
      macrocephaly, lower facial weakness, hypertelorism, downward slanting palpebral
      fissures, brachydactyly, and clinodactyly. SNP-microarray analysis revealed 516
      kb microduplication at 13q31.3 involving the entire MIR17HG gene encoding the miR
      17 ~ 92 polycistronic miRNA cluster, and the first five exons of the GPC5 gene.
      Family study confirmed that the microduplication was maternally inherited by the
      proband and one of his five half-brothers; digit and other skeletal anomalies
      were exclusive to the family members harboring the microduplication. This case
      represents the smallest reported microduplication to date at 13q31.3 and provides
      evidence supporting the important role of miR-17 ~ 92 gene dosage in normal
      growth and skeletal development. We postulate that any dosage abnormality of
      MIR17HG, either deletion or duplication, is sufficient to interrupt skeletal
      developmental pathway, with variable outcome from growth retardation to
      overgrowth. 

PMID- 24739088
TI  - Antagonism by salvianolic acid B of lipopolysaccharide-induced disseminated
      intravascular coagulation in rabbits.
AB  - The aim of the present study was to investigate the effects of salvianolic acid B
      on lipopolysaccharide (LPS)-induced disseminated intravascular coagulation (DIC)
      in rabbits. Continuous infusion of LPS was used to induce a DIC model in rabbits.
      Treatment with salvianolic acid B (1, 3 or 6 mg/kg) was started simultaneously
      with LPS infusion (0.5 mg/kg LPS in 60 mL saline; 10 mL/h over a period of 6 h)
      through the contralateral marginal ear vein. Activated partial thromboplastin
      time (APTT), prothrombin time (PT), platelet count and fibrinogen concentration
      were determined, as were plasma levels of fibrin-fibrinogen degradation products
      (FDP), alanine aminotransferase (ALT), blood urea nitrogen (BUN), protein C
      activity, antithrombin III (ATIII) and tumour necrosis factor (TNF)-alpha
      concentration. The gradual impairment of haemostatic parameters was induced by
      continuous infusion of LPS. There were marked increases in APTT, PT, BUN, ALT and
      plasma TNF-alpha and marked decreases in the platelet count, fibrinogen, FDP,
      protein C and ATIII. The intravenous administration of 1, 3 or 6 mg/kg
      salvianolic acid B attenuated the increases in APTT, PT, BUN, ALT and plasma TNF
      alpha and the decreases in fibrinogen, platelet, FDP, protein C and ATIII induced
      by LPS infusion. These observations indicate that salvianolic acid B has an
      effect against LPS-induced DIC in rabbits.

PMID- 24739089
TI  - Dearomative indole (3 + 2) cycloaddition reactions.
AB  - A diastereoselective (3 + 2) dearomative annulation of 3-substituted indoles with
      alpha-haloketones has been developed. Significant regiochemical control was
      observed. This methodology provides easy access to highly functionalized
      cyclopenta- or cyclohexa-fused indoline compounds, which are common structures of
      many natural products. The synthetic potential of this reaction was demonstrated
      in the concise syntheses of the core structures of vincorine, isocorymine, and
      aspidophylline A. DFT studies (B3LYP-D3/6-311++G**/MeOH) on cyclization
      mechanisms involving the 2-hydroxyallyl cation and its deprotonated oxyallyl
      cation have been performed. Under the reaction conditions, with a sparingly
      soluble Na2CO3 base, both species may be present and both pathways are viable.
      Both pathways support the formation of the experimentally observed O-bound
      intermediate, its transformation to the final product, the regiochemical and
      eventual stereochemical outcome of the kinetic cyclization product, and the
      thermodynamic preference for formation of the final stereoisomer. 

PMID- 24739090
TI  - Vitamin D, steroid hormones, and autoimmunity.
AB  - The endogenous serum metabolite of vitamin D (calcitriol, 1,25(OH)2 D3 ) is
      considered a true steroid hormone (D hormone), and like glucocorticoids (GCs) and
      gonadal hormones, may exert several immunomodulatory activities. Serum vitamin D
      deficiency (25(OH) D), and therefore reduced 1,25(OH)2 D3 availability, is
      considered a risk factor for several chronic/inflammatory or autoimmune
      conditions, including infectious diseases, type 1 diabetes, multiple sclerosis,
      and especially autoimmune rheumatic diseases (ARD). In ARD in particular,
      1,25(OH)2 D3 regulates both innate and adaptive immunity, potentiating the innate
      response (antimicrobial activity) but reducing adaptive immunity (antigen
      presentation, T and B cell activities). Regarding a possible synergism between
      vitamin D and GCs, several studies show that 1,25(OH)2 D3 has significant
      additive effects on dexamethasone-mediated inhibition of human lymphocyte and
      monocyte proliferation. Conversely, vitamin D deficiency seems to play a role in
      increasing autoantibody production by B cells, and seasonal vitamin D declines
      may trigger flares in ARD, as recently shown. Finally, 1,25(OH)2 D3 seems to
      reduce aromatase activity and limit the negative effects related to increased
      peripheral estrogen metabolism (cell proliferation, B cell overactivity). 

PMID- 24739091
TI  - Precipitants of heart failure must be fully considered when predicting
      readmission.

PMID- 24739093
TI  - Time-restricted feeding and risk of metabolic disease: a review of human and
      animal studies.
AB  - Time-restricted feeding (TRF), a key component of intermittent fasting regimens,
      has gained considerable attention in recent years. TRF allows ad libitum energy
      intake within controlled time frames, generally a 3-12 hour range each day. The
      impact of various TRF regimens on indicators of metabolic disease risk has yet to
      be investigated. Accordingly, the objective of this review was to summarize the
      current literature on the effects of TRF on body weight and markers of metabolic
      disease risk (i.e., lipid, glucoregulatory, and inflammatory factors) in animals
      and humans. Results from animal studies show TRF to be associated with reductions
      in body weight, total cholesterol, and concentrations of triglycerides, glucose,
      insulin, interleukin 6, and tumor necrosis factor-alpha as well as with
      improvements in insulin sensitivity. Human data support the findings of animal
      studies and demonstrate decreased body weight (though not consistently), lower
      concentrations of triglycerides, glucose, and low-density lipoprotein
      cholesterol, and increased concentrations of high-density lipoprotein
      cholesterol. These preliminary findings show promise for the use of TRF in
      modulating a variety of metabolic disease risk factors. 

PMID- 24739094
TI  - Harnessing microbiome and probiotic research in sub-Saharan Africa:
      recommendations from an African workshop.
AB  - To augment capacity-building for microbiome and probiotic research in Africa, a
      workshop was held in Nairobi, Kenya, at which researchers discussed human,
      animal, insect, and agricultural microbiome and probiotics/prebiotics topics.
      Five recommendations were made to promote future basic and translational research
      that benefits Africans. 

PMID- 24739095
TI  - Hyperuricemia and deterioration of renal function in autosomal dominant
      polycystic kidney disease.
AB  - BACKGROUND: The role of hyperuricemia in disease progression of autosomal
      dominant polycystic kidney disease (ADPKD) has not been defined well. We
      investigated the association of serum uric acid (sUA) with renal function and the
      effect of hypouricemic treatment on the rate of renal function decline. METHODS:
      This is a single-center, retrospective, observational cohort study. A total of
      365 patients with ADPKD who had estimated glomerular filtration rate (eGFR) >= 15
      mL/min/1.73 m2 and who were followed up for > 1 year were included in our
      analysis. Hyperuricemia was defined by a sUA level of >= 7.0 mg/dL in male and >=
      6.0 mg/dL in female or when hypouricemic medications were prescribed. RESULTS:
      Hyperuricemia was associated with reduced initial eGFR, independent of age, sex,
      hypertension, albuminuria, and total kidney volume. During a median follow-up
      period of over 6 years, patients with hyperuricemia showed a faster annual
      decline in eGFR (-6.3% per year vs. -0.9% per year, p = 0.008). However, after
      adjusting for age, sex, hypertension and initial eGFR, sUA was no longer
      associated with either annual eGFR decline or the development of ESRD. Among 53
      patients who received hypouricemic treatment, the annual eGFR decline appeared to
      be attenuated after hypouricemic treatment (pretreatment vs. posttreatment: -5.3
      +/- 8. 2 vs. 0.2 +/- 6.2 mL/min/1.73 m2 per year, p = 0.001 by Wilcoxon signed
      rank test). CONCLUSIONS: Although hyperuricemia was associated with reduced eGFR,
      it was not an independent factor for renal progression in ADPKD. However, the
      correction of hyperuricemia may attenuate renal function decline in some patients
      with mild renal insufficiency.

PMID- 24739096
TI  - Comparison of performances of five capillary blood collection tubes.
AB  - INTRODUCTION: The research demonstrated the way to compare performances of five
      capillary blood collection tubes for capillary blood collections among patients
      with pediatrics utilizing the Clinical and Laboratory Standards Institute (CLSI)
      document EP9-A2. METHODS: A questionnaire survey was distributed to evaluate the
      accessibility and reliability of capillary blood collection tubes from different
      sources. Visual examination, microscopic examination of blood smears, and
      instrumental analysis were performed to evaluate the blood sample quality in
      different tubes. The background test, comparison test, and reliability test were
      used to analyze the engineering quality and the performance of additives in the
      tubes, and to determine the reliability of the tubes in routine blood tests.
      RESULTS: The tubes of brand A were found to be easy to access, with a shorter
      blood collection time and greater acceptability by users, and the quality of
      blood samples in those tubes was superior, with no coagulation and less blood
      cell disruption. CONCLUSION: Commercially available capillary blood collection
      tubes were superior to 'in-house' tubes. In clinical practice, 'in-house'
      capillary blood collection tubes are not recommended. The guideline of 'method
      comparison and bias estimation using patient samples' from CLSI could also be
      used in comparing the performances of capillary blood collections.

PMID- 24739097
TI  - Serum uric acid is associated with coronary artery calcification.
AB  - Uric acid (UA) is associated with atherosclerosis, and coronary artery calcium
      (CAC) is a marker of atherosclerosis. The authors studied the association between
      UA and CAC. A total of 663 asymptomatic patients (564 men; mean age, 55+/-7
      years) were evaluated for the presence of CAC. The study population was divided
      into three tertiles according to their UA levels, and the prevalence of CAC was
      compared between the tertiles. CAC was detected in 349 (53%) patients. Levels of
      UA were significantly higher in those with CAC than in those without CAC (5.6+1.2
      vs 5.3+1.3; P=.003). The odds ratio for the presence of CAC in the highest vs
      lowest UA tertile was 1.72 (95% confidence interval, 1.17-2.51). The highest UA
      tertile remained associated with the presence of CAC after adjustment for known
      cardiovascular risk factors. The results show that high serum UA levels are
      associated with the presence of CAC.

PMID- 24739098
TI  - Enhanced saccadic control in young people with Tourette syndrome despite slowed
      pro-saccades.
AB  - Tourette syndrome (TS) is a neurodevelopmental disorder characterized by motor
      and vocal tics. Tics are repetitive and uncontrolled behaviours that have been
      associated with basal ganglia dysfunction. We investigated saccadic eye movements
      in a group of young people with TS but without co-morbid ADHD. Participants
      performed two tasks. One required them to perform only pro-saccade responses
      (pure pro-saccade task). The other involved shifting, unpredictably, between
      executing pro- and anti-saccades (mixed saccade task). We show that in the mixing
      saccade task, the TS group makes significantly fewer errors than an age-matched
      control group, while responding equally fast. By contrast, on the pure pro
      saccade task, the TS group were shown to be significantly slower to initiate and
      to complete the saccades (longer movement duration and decreased peak velocity)
      than controls, while movement amplitude and direction accuracy were not
      different. These findings demonstrate enhanced shifting ability despite slower
      reflexive responding in TS and are discussed with respect to a disorder-related
      adaptation for increased cognitive regulation of behaviour. 

PMID- 24739099
TI  - Experiences of barriers and facilitators to weight-loss in a diet intervention -
      a qualitative study of women in northern Sweden.
AB  - BACKGROUND: There is a lack of research about the experiences of participating in
      weight-reducing interventions. The aim of this study was to explore barriers and
      facilitators to weight-loss experienced by participants in a diet intervention
      for middle-aged to older women in the general population in Northern Sweden.
      METHOD: In the intervention the women were randomised to eat either a
      Palaeolithic-type diet or a diet according to Nordic Nutrition recommendations
      for 24 months. A strategic selection was made of women from the two intervention
      groups as well as from the drop-outs in relation to social class, civil status
      and age. Thematic structured interviews were performed with twelve women and
      analysed with qualitative content analyses. RESULTS: The results showed that the
      women in the dietary intervention experienced two main barriers - struggling with
      self (related to difficulties in changing food habits, health problems, lack of
      self-control and insecurity) and struggling with implementing the diet (related
      to social relations and project-related difficulties) - and two main facilitators
      striving for self-determination (related to having clear goals) and receiving
      support (from family/friends as well as from the project) - for weight-loss.
      There was a greater emphasis on barriers than on facilitators. CONCLUSION: It is
      important to also include drop-outs from diet interventions in order to fully
      understand barriers to weight-loss. A gender-relational approach can bring new
      insights into understanding experiences of barriers to weight-loss. TRIAL
      REGISTRATION: ClinicalTrials gov NCT00692536.

PMID- 24739100
TI  - Acute generalized exanthematous pustulosis induced by clopidogrel.

PMID- 24739101
TI  - Proton-coupled protein binding: controlling lysozyme/poly(acrylic acid)
      interactions with pH.
AB  - Rational design of protein-polymer composites and their use, under the influence
      of the stimulus, for numerous applications requires a clear understanding of
      protein-polymer interfaces. Here, using poly(acrylic acid) (PAA) and lysozyme as
      model systems, the binding interactions between these macromolecules were
      investigated by isothermal titration calorimetry. The binding is proposed to
      require and be governed by "charge neutralization of the protein/polymer
      interface" and predicted to depend on solution pH. Calorimetric data show strong
      exothermic binding of lysozyme to PAA with a molar DeltaH and TDeltaS values of 
      107 and -95 kcal/mol, respectively, at pH 7 and room temperature. Both DeltaH and
      TDeltaS decreased linearly with increasing pH from 3 to 8, and these plots had
      slopes of -17.7 and -17.5 kcal/mol per pH unit, respectively. The net result was
      that the binding propensity (DeltaG) was nearly independent of pH but the binding
      stoichiometry, surprisingly, increased rapidly with increasing pH from 1 lysozyme
      binding per PAA molecule at pH 3 to 16 lysozyme molecules binding per PAA
      molecule at pH 8. A plot of stoichiometry vs pH was linear, and consistent with
      this result, a plot of ln(average size of the protein/polymer complex) vs pH was
      also linear. Thus, protonation-deprotonation plays a major role in the binding
      mechanism. "Charge neutralization" of the lysozyme/PAA interface controls the
      binding stoichiometry as well as the binding enthalpies/entropies in a
      predictable fashion, but it did not control the binding affinity (DeltaG). The pH
      dependence of lysozyme binding to PAA, demonstrated here, provides a stimuli
      responsive system for protein binding and release from the polymer surface. 

PMID- 24739103
TI  - Latitudinal variation in the degree of crassulacean acid metabolism in Puya
      chilensis.
AB  - Crassulacean acid metabolism (CAM) is a photosynthetic pathway found in many
      plant species from arid and semiarid environments. Few studies aiming to
      characterise plant species as CAM or C3 account for inter-population differences
      in photosynthetic pathway, often relying on samples taken from herbarium material
      and/or a single plant or population. This may be especially problematic for
      species growing under contrasting climate conditions, as is the case for species
      with a wide geographic range. We used Puya chilensis, a species previously
      reported as CAM and C3, to study among-population variation in expression of the
      CAM pathway within its distribution range, which spans a significant climate
      gradient. We carried out a wide sampling scheme, including five populations and a
      combination of analytical methods (quantification of nocturnal acidification and
      stable isotope measurements). The study populations of P. chilensis encompass the
      entire latitudinal distribution range, from semi-arid to temperate oceanic
      climates. Our results indicate that CAM decreased with latitude. However, even in
      the southern (wetter) populations, where delta13C values were indicative of C3
      metabolism, we found some nocturnal acidification. We stress the value of using
      two methods along with the use of samples from different populations, as this
      allows more reliable conclusions on the photosynthetic pathway for 'probable' CAM
      species that face varying climate conditions within their distribution ranges.

PMID- 24739102
TI  - Density drives polyandry and relatedness influences paternal success in the
      Pacific gooseneck barnacle, Pollicipes elegans.
AB  - BACKGROUND: Polyandry is a common mating strategy in animals, increasing female
      fitness through direct (material) and indirect (genetic) benefits. Most theories
      about the benefits of polyandry come from studies of terrestrial animals, which
      have relatively complex mating systems and behaviors; less is known about the
      potential benefits of polyandry in sessile marine animals, for which potential
      mates may be scarce and females have less control over pre-copulatory mate
      choice. Here, we used microsatellite markers to examine multiple paternity in
      natural aggregations of the Pacific gooseneck barnacle Pollicipes elegans,
      testing the effect of density on paternity and mate relatedness on male
      reproductive success. RESULTS: We found that multiple paternity was very common
      (79% of broods), with up to five fathers contributing to a brood, though power
      was relatively low to detect more than four fathers. Density had a significant
      and positive linear effect on the number of fathers siring a brood, though this
      relationship leveled off at high numbers of fathers, which may reflect a lack of
      power and/or an upper limit to polyandry in this species. Significant skew in
      male reproductive contribution in multiply-sired broods was observed and we found
      a positive and significant relationship between the proportion of offspring sired
      and the genetic similarity between mates, suggesting that genetic compatibility
      may influence reproductive success in this species. CONCLUSIONS: To our
      knowledge, this is the first study to show high levels of multiple paternity in a
      barnacle, and overall, patterns of paternity in P. elegans appear to be driven
      primarily by mate availability. Evidence of paternity bias for males with higher
      relatedness suggests some form of post-copulatory sexual selection is taking
      place, but more work is needed to determine whether it operates during or post
      fertilization. Overall, our results suggest that while polyandry in P. elegans is
      driven by mate availability, it may also provide a mechanism for females to
      ensure fertilization by compatible gametes and increase reproductive success in
      this sessile species.

PMID- 24739105
TI  - Banking on wellness. Practices try out monthly payment plans to promote
      preventive care.

PMID- 24739106
TI  - Buy-in needed for one health concept to work.

PMID- 24739107
TI  - Are we really doing enough to provide the best veterinary care for our pets?

PMID- 24739108
TI  - Antiparasitic resistance and grazing livestock in the United States.

PMID- 24739109
TI  - What is your diagnosis? Cutaneous periorbital sarcoids.

PMID- 24739110
TI  - What is your diagnosis? Keratoacanthoma.

PMID- 24739111
TI  - ECG of the Month. Third degree atrioventricular block.

PMID- 24739112
TI  - Pathology in practice. HaPyV infection in a pet Syrian hamster.

PMID- 24739113
TI  - Postoperative comparison of four perioperative analgesia protocols in dogs
      undergoing stifle joint surgery.
AB  - OBJECTIVE: To compare 4 analgesic protocols in dogs undergoing stifle joint
      surgery. DESIGN: Randomized, blinded, prospective clinical trial. Animals-48
      client-owned dogs that underwent stifle joint surgery. PROCEDURES: Dogs
      undergoing tibial plateau leveling osteotomy were randomly assigned to receive a
      constant rate infusion of a combination of morphine, lidocaine, and ketamine; a
      lumbosacral epidural with morphine and ropivacaine; both treatments (ie, constant
      rate infusion and lumbosacral epidural); or only IM premedication with morphine.
      Indices of cardiorespiratory function and isoflurane requirement were recorded at
      5-minute intervals during anesthesia. A validated sedation scoring system and the
      modified Glasgow composite measure pain score were used to assess comfort and
      sedation after surgery and anesthesia once the swallowing reflex returned and a
      body temperature of >= 36.7 degrees C (98.1 degrees F) was attained. Pain and
      sedation scores were acquired at 60-minute intervals for 4 hours, then at 4-hour
      intervals for 24 hours. Dogs with a postoperative pain score > 5 of 24 were given
      morphine as rescue analgesia. RESULTS: No differences in heart rate, respiratory
      rate, systolic arterial blood pressure, end-tidal Pco2, end-tidal isoflurane
      concentration, and vaporizer setting were detected among groups. No differences
      in pain score, sedation score, rescue analgesia requirement, or time to first
      rescue analgesia after surgery were detected. CONCLUSIONS AND CLINICAL RELEVANCE:
      Pain scores were similar among groups, and all 4 groups had similar rescue
      analgesia requirements and similar times to first administration of rescue
      analgesia. All 4 analgesic protocols provided acceptable analgesia for 24 hours
      after stifle joint surgery.

PMID- 24739114
TI  - Prevalence of deafness and association with coat variations in client-owned
      ferrets.
AB  - OBJECTIVE: To evaluate the prevalence of congenital sensorineural deafness (CSD)
      and its association with phenotypic markers in client-owned ferrets. DESIGN:
      Epidemiological study. ANIMALS: 152 healthy European pet ferrets. PROCEDURES:
      Brainstem auditory evoked response tests were recorded in ferrets during general
      anesthesia. Phenotypic markers such as sex, coat color and pattern, coat length
      (Angora or not), and premature graying trait were assessed. RESULTS: Overall, 44
      of the 152 (29%) ferrets were affected by CSD; 10 (7%) were unilaterally deaf,
      and 34 (22%) were bilaterally deaf. There was no association between CSD and sex
      or Angora trait, but a strong association between CSD and white patterned coat or
      premature graying was identified. All panda, American panda, and blaze ferrets
      were deaf. CONCLUSIONS AND CLINICAL RELEVANCE: The ferrets in this study had a
      high prevalence of CSD that was strictly associated with coat color patterns,
      specifically white markings and premature graying. This seemed to be an emerging
      congenital defect in pet ferrets because white-marked coats are a popular new
      coat color. Breeders should have a greater awareness and understanding of this
      defect to reduce its prevalence for the overall benefit of the species.

PMID- 24739115
TI  - Osteosarcoma following tibial plateau leveling osteotomy in dogs: 29 cases (1997
      2011).
AB  - OBJECTIVE: To determine the signalment, tibial plateau leveling osteotomy (TPLO)
      plate type, clinical staging information, treatment, and oncological outcome in
      dogs that developed osteosarcoma at the proximal aspect of the tibia following
      TPLO and to calculate the interval between TPLO and osteosarcoma diagnosis.
      DESIGN: Multi-institutional retrospective case series. ANIMALS: 29 dogs.
      PROCEDURES: Medical records from 8 participating institutions were searched for
      dogs that developed osteosarcoma (confirmed through cytologic or histologic
      evaluation) at previous TPLO sites. Signalment, TPLO details, staging tests,
      treatment data, and outcome information were recorded. Descriptive statistics
      were calculated, and disease-free intervals and survival times were evaluated by
      means of Kaplan-Meier analysis. RESULTS: 29 dogs met the inclusion criteria. The
      mean age was 9.2 years and mean weight was 45.1 kg (99.2 lb) at the time of
      osteosarcoma diagnosis. Most dogs had swelling over the proximal aspect of the
      tibia (17/21) and lameness of the affected limb (28/29). The mean interval
      between TPLO and osteosarcoma diagnosis was 5.3 years. One type of cast stainless
      steel TPLO plate was used in most (18) dogs; the remaining dogs had received
      plates of wrought stainless steel (n = 4) or unrecorded type (7). Twenty-three of
      29 dogs underwent treatment for osteosarcoma. Median survival time for 10 dogs
      that underwent amputation of the affected limb and received >= 1 chemotherapeutic
      treatment was 313 days. CONCLUSIONS AND CLINICAL RELEVANCE: Results supported
      that osteosarcoma should be a differential diagnosis for dogs with a history of
      TPLO that later develop lameness and swelling at the previous surgical site.
      Oncological outcome following amputation and chemotherapy appeared to be similar
      to outcomes previously reported for dogs with appendicular osteosarcoma.

PMID- 24739116
TI  - Agreement of serum feline pancreas-specific lipase and colorimetric lipase assays
      with pancreatic ultrasonographic findings in cats with suspicion of pancreatitis:
      161 cases (2008-2012).
AB  - OBJECTIVE: To investigate agreement of a feline pancreas-specific lipase assay
      and a colorimetric lipase assay with a 1,2-o-dilauryl-rac-glycero-3-glutaric acid
      (6'-methylresorufin) ester (DGGR) substrate with results of pancreatic
      ultrasonography in cats with suspicion of pancreatitis. DESIGN: Retrospective
      case series. ANIMALS: 161 client-owned cats with suspicion of pancreatitis.
      PROCEDURES: Feline pancreas-specific lipase concentration and DGGR lipase
      activity were measured from the same blood sample in cats undergoing
      investigation for pancreatitis, with < 24 hours between ultrasonography and
      lipase determinations. Ultrasonographic variables evaluated were ultrasonographic
      diagnosis of pancreatitis, enlargement, margins, echogenicity, mesenteric
      echogenicity, peripancreatic free fluid, cysts, masses, and common bile and
      pancreatic duct dilation. Agreement was assessed by use of the Cohen kappa
      coefficient. RESULTS: Agreement between the lipase assays was substantial (kappa
      = 0.703). An ultrasonographic diagnosis of pancreatitis had fair agreement with
      feline pancreas-specific lipase concentration > 5.4 MUg/L (kappa = 0.264) and
      DGGR lipase activity > 26 U/L (kappa = 0.221). The greatest agreement between
      feline pancreas-specific lipase concentration > 5.4 MUg/L and DGGR lipase
      activity > 26 U/L was found for a hypoechoic and mixed-echoic (kappa = 0.270 and
      0.266, respectively), hypoechoic (kappa = 0.261 and 0.181, respectively), and
      enlarged (kappa = 0.218 and 0.223, respectively) pancreas. CONCLUSIONS AND
      CLINICAL RELEVANCE: Agreement between pancreatic ultrasonography and lipase assay
      results was only fair. It remains unknown whether lipase results or pancreatic
      ultrasonography constitutes the more accurate test for diagnosing pancreatitis;
      therefore, results of both tests need to be interpreted with caution.

PMID- 24739117
TI  - Direct and indirect contact rates among livestock operations in Colorado and
      Kansas.
AB  - OBJECTIVE: To characterize direct and indirect contacts among livestock
      operations in Colorado and Kansas. DESIGN: Cross-sectional quarterly survey.
      SAMPLE: 532 livestock producers. PROCEDURES: Livestock producers in Colorado and
      Kansas were recruited by various means to participate in the survey, which was
      sent out via email or postal mail once quarterly (in March, June, September, and
      December) throughout 2011. Data were entered into an electronic record, and
      descriptive statistics were summarized. RESULTS: Large swine operations moving
      animals to other large swine operations had the highest outgoing direct contact
      rates (range, 5.9 to 24.53/quarter), followed by dairy operations moving cattle
      to auction or other dairy operations (range, 2.6 to 10.34/quarter). Incoming
      direct contact rates for most quarters were highest for large feedlots (range, 0
      to 11.56/quarter) and dairies (range, 3.90 to 5.78/quarter). For large feedlots,
      mean total indirect contacts through feed trucks, livestock haulers, and manure
      haulers each exceeded 725 for the year. Dairy operations had a mean of 434.25
      indirect contacts from milk trucks and 282.25 from manure haulers for the year.
      CONCLUSIONS AND CLINICAL RELEVANCE: High direct contact rates detected among
      large swine operations may suggest a risk for direct disease transmission within
      the integrated swine system. Indirect contacts as well as incoming direct
      contacts may put large feedlots at substantial risk for disease introduction.
      These data can be useful for establishing and evaluating policy and biosecurity
      guidelines for livestock producers in the central United States. The results may
      be used to inform efforts to model transmission and control of infectious
      diseases such as foot-and-mouth disease in this region.

PMID- 24739118
TI  - Type II error and statistical power in reports of small animal clinical trials.
AB  - OBJECTIVE: To describe reporting of key methodological elements associated with
      type II error in published reports of small animal randomized controlled trials
      (RCTs) and to determine the statistical power in a subset of RCTs with negative
      results. DESIGN: Descriptive literature survey. SAMPLE: Reports of parallel-group
      clinical RCTs published in 11 English-language veterinary journals from 2005 to
      2012. PROCEDURES: Predefined criteria were used to identify trial primary
      outcomes and classify results as negative or positive. Details of sample size
      determination and use of confidence intervals in results reporting were recorded.
      For each 2-group RCT with negative results, the statistical power to detect 25%
      and 50% relative differences in outcome was calculated. RESULTS: Of 238 RCTs, 42
      (18%) stated a primary outcome, 52 (22%) reported a sample size calculation, and
      18 (9%) included a confidence interval around the observed treatment effect.
      Reports of only 2 (0.8%) RCTs included all 3 elements. Among 103 two-group RCTs
      with negative results, only 14 (14%) and 40 (39%) were sufficiently powered (beta
      < 0.20) to detect 25% and 50% relative differences in outcome between treatments,
      respectively. CONCLUSIONS AND CLINICAL RELEVANCE: The present survey found that
      small animal RCTs with negative results were often underpowered to detect
      moderate-to-large effect sizes between study groups. Information needed for
      critical appraisal was missing from most reports. The potential for clinicians to
      base treatment decisions on inappropriate interpretations of RCTs was worrisome.
      Design and reporting of small animal RCTs must be improved.

PMID- 24739119
TI  - Morphological and molecular analyses of larval and adult stages of
      Echinoparyphium recurvatum von Linstow 1873 (Digenea: Echinostomatidae) from
      central Mexico.
AB  - In central Mexico, populations of the freshwater snail Physella cubensis were
      infected with metacercariae from a species of Echinoparyphium (Digenea:
      Echinostomatidae). In the current study, we describe both larval and adult stages
      of this species obtained from experimental and natural infections. A total 180
      snails were collected from Patzcuaro Lake, Michoacan state in central Mexico in
      July 2012. In the laboratory snails were placed in individual vials and exposed
      to light with the aim of observing emergence of cercariae. To obtain
      metacercariae, uninfected snails (P. cubensis) were exposed to cercariae. Chicks
      were infected with metacercariae to obtain adults. Nine days post-infection, eggs
      were recovered and incubated in tap water at room temperature to observe
      miracidia. Adults obtained from natural and experimentally infected hosts possess
      a head collar with 45 spines in two alternating rows, confirming the
      identification as Echinoparyphium recurvatum von Linstow 1873. To test the
      conspecificity of all stages, sequences of nuclear internal transcribed spacer 1
      (ITS1), 5.8S and ITS2 rDNA were obtained from two adult worms recovered from
      chicks and also a natural avian host, the shoveler duck Anas clypeata, together
      with five cercarial and four metacercarial isolates from nine snails. The genetic
      divergence estimated among the 13 isolates was very low, ranging from 0 to 0.6%.
      Phylogenetic analyses inferred by maximum likelihood and Bayesian methods showed
      that all isolates of E. recurvatum form a single clade with strong support. The
      presence of E. recurvatum in P. cubensis and A. clypeata from central Mexico
      represents new host reports, and extends the distribution range in the Americas. 

PMID- 24739120
TI  - Copper-catalyzed intermolecular C-H amination of (hetero)arenes via transient
      unsymmetrical lambda3-iodanes.
AB  - A one-pot two-step method for intermolecular C-H amination of electron-rich
      heteroarenes and arenes has been developed. The approach is based on a room
      temperature copper-catalyzed regioselective reaction of the in situ formed
      unsymmetrical (hetero)aryl-lambda(3)-iodanes with a wide range of primary and
      secondary aliphatic amines and anilines. 

PMID- 24739121
TI  - Systemic effects induced by intralesional injection of omega-conotoxin MVIIC
      after spinal cord injury in rats.
AB  - BACKGROUND: Calcium channel blockers such as conotoxins have shown a great
      potential to reduce brain and spinal cord injury. MVIIC neuroprotective effects
      analyzed in in vitro models of brain and spinal cord ischemia suggest a potential
      role of this toxin in preventing injury after spinal cord trauma. However,
      previous clinical studies with MVIIC demonstrated that clinical side effects
      might limit the usefulness of this drug and there is no research on its systemic
      effects. Therefore, the present study aimed to investigate the potential toxic
      effects of MVIIC on organs and to evaluate clinical and blood profiles of rats
      submitted to spinal cord injury and treated with this marine toxin. Rats were
      treated with placebo or MVIIC (at doses of 15, 30, 60 or 120 pmol)
      intralesionally following spinal cord injury. Seven days after the toxin
      administration, kidney, brain, lung, heart, liver, adrenal, muscles, pancreas,
      spleen, stomach, and intestine were histopathologically investigated. In
      addition, blood samples collected from the rats were tested for any hematologic
      or biochemical changes. RESULTS: The clinical, hematologic and biochemical
      evaluation revealed no significant abnormalities in all groups, even in high
      doses. There was no significant alteration in organs, except for degenerative
      changes in kidneys at a dose of 120 pmol. CONCLUSIONS: These findings suggest
      that MVIIC at 15, 30 and 60 pmol are safe for intralesional administration after
      spinal cord injury and could be further investigated in relation to its
      neuroprotective effects. However, 120 pmol doses of MVIIC may provoke adverse
      effects on kidney tissue.

PMID- 24739122
TI  - Macro/Nano-gel composite as an injectable and bioactive bulking material for the
      treatment of urinary incontinence.
AB  - Many women around the world are suffering from urinary incontinence, defined as
      the unintentional leakage of urine by external abnormal pressure. Although
      various kinds of materials have been utilized to treat this disease, therapies
      that are more effective are still needed for the treatment of urinary
      incontinence. Here, we present a macro/nanogel composed of in situ forming
      gelatin-based macrogels and self-assembled heparin-based nanogels, which can
      serve as an injectable and bioactive bulking material for the treatment of
      urinary incontinence. The hybrid hydrogels were prepared via enzymatic reaction
      in the presence of horseradish peroxidase and hydrogen peroxide. Incorporating a
      growth factor (GF)-loaded heparin nanogel into a gelatin gel matrix enabled the
      hybrid gel matrix to release GF continuously up to 28 days. Moreover, we
      demonstrated that the hydrogel composites stimulated the regeneration of the
      urethral muscle tissue surrounding the urethral wall and promoted the recovery of
      their biological function when injected in vivo. Thus, the macro/nanohydrogels
      may provide an advanced therapeutic technique for the treatment of urinary
      incontinence as well as an application for regenerative medicine. 

PMID- 24739123
TI  - Rare copy number variations containing genes involved in RASopathies: deletion of
      SHOC2 and duplication of PTPN11.
AB  - BACKGROUND: RASopathies are a group of disorders related to Noonan syndrome that
      with dysregulated RAS-mitogen-activated protein kinase (MAPK) signaling pathway.
      Noonan syndrome (NS, OMIM# 163950) is a both phenotypically and genotypically
      variable disorder. We and other researchers have demonstrated that copy number
      variations underlie a small percentage of patients with RASopathies. RESULTS: In
      a cohort of 12 clinically characterized patients with congenital heart defect
      (CHD) and features suggestive of Noonan syndrome or Noonan like syndrome without
      known causative gene mutation, we performed an Illumina SNP-array analysis to
      identify the pathogenic copy number variations (Human660W-Quad Chip, Beadstation
      Scanner and GenomeStudio V2011 software). We identifed two rare copy number
      variations harboring genes involved in RAS- MAPK signaling pathway of RASopathy.
      One is a 24 Mb duplication of 12q24.1-24.3 containing PTPN11 and the other is a
      183 kb deletion of 10q25.2 including SHOC2. The SNP-array results were further
      validated by quantitative PCR (qPCR). This is might be the first report
      suggesting that haploinsufficiency of SHOC2 can result in a RASopathy-like
      phenotype. CONCLUSIONS: Our findings provide additional support that copy number
      variations containing disease-causing genes of RAS/MAPK pathway play a minor role
      in RASopathies or related disorders. We recommend the use of microarrays in
      Noonan syndrome like patients without identified mutations in the causative
      genes.

PMID- 24739124
TI  - Perceptual presence without counterfactual richness.
AB  - In this commentary, I suggest that non-visual perceptual modalities provide
      counterexamples to Seth's claim that perceptual presence depends on
      counterfactual richness. Then I suggest a modification to Seth's view that is not
      vulnerable to these counterexamples.

PMID- 24739125
TI  - Molecular diagnosis and the Italian Board for ISAC.
AB  - The Component Resolved Diagnostic (CRD) approach has been developed when highly
      purified or recombinant allergen molecules have become available. These molecules
      are the allergenic proteins toward which the specific and clinically relevant IgE
      immune response is directed. So, the identification of protein families and cross
      reactivity patterns of importance in allergy have been possible. The Italian
      advisory BOARD for ISAC was born: to evaluate the advantages, disadvantages and
      placement in diagnosis of CRD studying its application in allergic patients; to
      facilitate the interpretation of molecular diagnostics for clinical allergists;
      to evaluate the effectiveness of CRD in improving diagnostic risk assessment and
      early preventive treatment of allergic diseases. In the last years, its fields of
      interest have been: the evaluation of the performance of CRD on multi-sensitized
      allergic patients with respiratory symptoms and on poly-sensitized athletes; the
      evolution of IgE repertoire directed to single allergenic components by
      evaluating allergic patients with different age at a molecular level; the
      relevance of results obtained using allergen microarray technique for describing
      the IgE repertoire in allergic patients by reviewing the main articles focused on
      CRD published in the last 2 years; the need for an educational program focused on
      this new diagnostic tool also through the creation of an exhaustive and
      interactive explanation of the laboratory report molecular allergy; the
      investigation of the performance and potential additional diagnostic values of
      the ISAC microarray in a real-life clinical setting, taking into account also the
      economic values. 

PMID- 24739126
TI  - Asthma management among different specialists: results from a national Italian
      survey.
AB  - In Europe more than 50% of asthmatic treated patients have a not well-controlled
      asthma. The present survey aims at investigating how different specialists
      approach asthmatic patients. A web anonymous questionnaire was randomly
      administered to 604 General Practitioners (GPs), 241 Pneumologists and 131
      Allergists. It concerned: epidemiology, diagnostic workup, follow-up and risk
      factors, treatment and future risk. A general agreement emerges about asthma
      diagnostic work-up. All categories are aware of the impact of comorbidities on
      asthma. LABA/inhaled steroids combination is considered the first choice
      treatment. Surprisingly, depot steroids and long-acting beta2 agonists (LABA)
      alone are still prescribed by GPs. Concerning monitoring tools, Allergists rely
      on inflammation biomarkers, whereas reduction of rescue medication is more
      relevant for GPs. Asthma Control Test (ACT) is considered time consuming by more
      than 50% of all physicians and is not known by most of GPs. Adherence is
      considered a crucial problem in asthma management. All categories seem to have a
      good knowledge about asthma. The cultural background may account for mild
      differences in asthma control tools and treatment options. GPs have a pivotal
      role in discriminating patients who need specific assessment by specialists. It
      is thus important that GPs and specialists share common tools for recognizing and
      managing those patients. 

PMID- 24739127
TI  - The perception of allergen-specific immunotherapy among Italian general
      practitioners.
AB  - BACKGROUND: Allergen specific immunotherapy is the only causal therapy for
      respiratory allergies, and the only treatment that can modify the natural course
      of the disease. Information and education of patients is essential to successful
      treatment and, since the General Practitioner is the primary referral, a
      cooperation between him and the allergy specialists is crucial. We carried out a
      survey among Italian GPs to assess their knowledge about immunotherapy and their
      attitude towards it. METHOD: A 12-item questionnaire on specific immunotherapy,
      based on guidelines and literature, was prepared by a panel of experts and
      anonymously e-mailed to 200 GPs of the Italian Society of General Practitioners.
      RESULTS: Out of 200 questionnaires, 156 were returned and 126 could be evaluated.
      The 126 respondents accounted for a population of about 300,000 patients. The
      overall knowledge on subcutaneous and sublingual immunotherapy resulted to be
      satisfactory and the attitude towards immunotherapy was generally favourable. On
      the other hand, only less than 50% of GPs were aware of the exact placement of
      immunotherapy in international guidelines and all considered a more detailed
      information on the treatment necessary. CONCLUSION: There is still room for
      improving the knowledge on specific immunotherapy among general practitioners.
      This would allow a better synergy between primary care operators and specialists.

PMID- 24739128
TI  - Costs of treatment affect compliance to specific subcutaneous immunotherapy.
AB  - BACKGROUND: Specific subcutaneous immunotherapy (SCIT) is cost-effective; however
      its economical burden can lead to non-adherence. We aimed to identify the
      reported reasons, patient's personal or socio-demographic characteristics and
      SCIT-related factors associated with non-adherence to SCIT. METHODS: This is a
      cross-sectional, observational study held in a Portuguese University Hospital.
      All records from patients starting SCIT in the last 4 years were reviewed in July
      2011. Those without registry of SCIT administration in the previous 3 months were
      included (n = 181). A telephonic survey was performed and 56 were confirmed as
      non-adherent; reasons for discontinuation were assessed. Univariate and multiple
      logistic regression models were developed using characteristics previously
      described as being associated with non-adhesion. RESULTS: Economical burden of
      SCIT was the most important factor leading to treatment discontinuation (40%). In
      the univariate analysis, presence of family history of allergic disease treated
      with immunotherapy was associated with decreased OR of non-adherence to SCIT (OR
      [95%CI] = 0.31 [0.11- 0.88]). In the multiple logistic regression model, none of
      the factors was significantly associated with non-adherence. CONCLUSION:
      Adherence is influenced by economic factors. More attention should be given to
      the impact of economic changes in allergic patient's treatment.

PMID- 24739129
TI  - Exercise-induced anaphylaxis in a cardiopathic patient on chronic aspirin
      therapy.
AB  - We report the case of a 73 year old man on chronic aspirin therapy who went in
      anaphylactic shock during his daily farm chores following a meal rich in wheat
      products. The serum specific IgE assay (ImmunoCAP) showed strong positive
      specific IgE responses to omega-5 gliadin. A two-year period avoiding wheat meals
      3 hours prior to exercise, resulted in a lack of further anaphylaxis; this
      results aided us in making the diagnosis. 

PMID- 24739130
TI  - Ambulatory pulse oximetry monitoring in Japanese COPD outpatients not receiving
      oxygen therapy.
AB  - BACKGROUND: It remains unknown whether desaturation profiles during daily living
      are associated with prognosis in patients with chronic obstructive pulmonary
      disease (COPD). Point measurements of resting oxygen saturation by pulse oximetry
      (SpO2) and partial pressure of arterial oxygen (PaO2) are not sufficient for
      assessment of desaturation during activities of daily living. A small number of
      studies continuously monitored oxygen saturation throughout the day during
      activities of daily living in stable COPD patients. This study aims to analyse
      the frequency of desaturation in COPD outpatients, and investigate whether the
      desaturation profile predicts the risk of exacerbation. METHODS: We studied
      stable COPD outpatients not receiving supplemental oxygen therapy. Baseline
      assessments included clinical assessment, respiratory function testing, arterial
      blood gas analysis, body mass index, and the COPD Assessment Test (CAT). Patients
      underwent 24-hour ambulatory monitoring of SpO2 during activities of daily
      living. Exacerbations of COPD and death from any cause were recorded. RESULTS:
      Fifty-one patients were enrolled in the study, including 12 current smokers who
      were excluded from the analyses in case high serum carboxyhaemoglobin
      concentrations resulted in inaccurately high SpO2 readings. The mean percent
      predicted forced expiratory volume in one second (%FEV1) was 50.9%. The mean
      proportion of SpO2 values below 90% was 3.0% during the day and 7.4% during the
      night. There were no daytime desaturators, defined as >= 30% of daytime SpO2
      values below 90%. Twenty-one exacerbations occurred in 13 patients during the
      mean follow-up period of 26.4 months. Univariate and multivariate Cox
      proportional hazards analyses did not detect any significant factors associated
      with exacerbation. CONCLUSIONS: Our 24-hour ambulatory oximetry monitoring
      provided precise data regarding the desaturation profiles of COPD outpatients.
      Both daytime and nighttime desaturations were infrequent. The proportion of
      ambulatory SpO2 values below 90% was not a significant predictor of exacerbation.

PMID- 24739131
TI  - Impact of short-term low-dose atorvastatin on low-density lipoprotein and high
      density lipoprotein subfraction phenotype.
AB  - Statins can significantly reduce low-density lipoprotein-cholesterol (LDL-C) and
      modestly raise or not alter high-density lipoprotein-cholesterol (HDL-C).
      However, their impact on high-density lipoprotein (HDL) and low-density
      lipoprotein (LDL) subfractions has been less examined. The aim of the present
      study was to investigate the short-term impact of low-dose atorvastatin on HDL
      and LDL subfractions in humans. In this randomized study, data from 52 subjects
      were analysed. Thirty-seven patients with atherosclerosis were randomized to
      treatment with atorvastatin 10 mg/day (n = 17) or 20 mg/day (n = 20) for 8 weeks,
      with 15 healthy subjects without therapy used as a control group. The lipid
      profile and lipoprotein subfractions were determined using the Lipoprint system
      at baseline and at 8 weeks. The data suggest that atorvastatin treatment (10 and
      20 mg/day) for 8 weeks significantly decreases LDL-C levels and reduces the
      cholesterol concentration of all LDL subfractions, which is accompanied by an
      increase of the mean LDL particle size. Although 10 mg/day atorvastatin treatment
      for 8 weeks had no impact on the HDL subfraction, 20 mg/day atorvastatin for 8
      weeks significantly increased the cholesterol concentration of large HDL
      particles and decreased the cholesterol concentration of small HDL particles
      without changing serum HDL-C levels in patients with atherosclerosis. Therefore,
      the results suggest that 20 mg/day atorvastatin treatment for 8 weeks may result
      in a favourable modification of the HDL subfraction phenotype in addition to its
      effects on the cholesterol concentration of all LDL subfractions and mean LDL
      particle size.

PMID- 24739132
TI  - Reference intervals for immature platelet fraction and immature platelet count.

PMID- 24739133
TI  - Factors that affect zinc bioavailability and losses in adult and elderly
      populations.
AB  - The most widely used method for estimating dietary zinc requirements is the
      factorial approach, in which it is assumed, in adults, that the physiological
      zinc requirement is the lowest intake that replaces endogenous zinc losses.
      Presented here are the results of two reviews: a narrative review of zinc losses
      from the human body and a systematic review of factors affecting zinc
      bioavailability in adult and elderly populations. The narrative review presents
      data on losses from integumental and excretory routes, obtained from 29 papers
      published up to April 2013. The systematic review includes a total of 87
      publications describing dietary factors that impact zinc bioavailability, 30 of
      which examined phytate. A meta-analysis revealed an overall lowering of
      fractional zinc absorption by 0.14 (45% of control values) when the phytate :
      zinc molar ratio of the test meal or diet was greater than 15. These reviews
      provide a comprehensive resource for use in the setting of human dietary zinc
      requirements and emphasize the need for more high-quality data to improve
      estimates of zinc losses and gains.

PMID- 24739134
TI  - Intra-aortic balloon pump for treatment of refractory ventricular tachycardia in
      Tako-Tsubo cardiomyopathy: a case report.

PMID- 24739135
TI  - Ipsilateral foetal-type posterior cerebral artery is associated with cognitive
      decline after carotid revascularisation.
AB  - BACKGROUND: Stenosis of the internal carotid artery has been associated with
      cognitive impairment and decline. However, studies testing the effect of carotid
      revascularisation on cognition have had conflicting results. This may in part be
      explained by variation in the flow territory of the carotid artery. In 12 to 36%
      of the patients, the posterior cerebral artery is mainly or exclusively supplied
      by the internal carotid artery via a foetal-type posterior cerebral artery. In
      these patients, ipsilateral carotid artery stenosis is likely to result in a
      larger area with hypoperfusion than in case of a normal posterior cerebral
      artery. Patients with a foetal-type posterior cerebral artery could therefore
      benefit more from revascularisation. We compared the effects of carotid
      revascularisation on cognition between patients with a foetal-type and those with
      a normal posterior cerebral artery. METHODS: Patients with symptomatic internal
      carotid artery stenosis >= 50%, enrolled in the International Carotid Stenting
      Study (ICSS) at a single centre, underwent detailed neuropsychological
      examinations before and 6 months after revascularisation. Cognitive test results
      were standardized into z-scores, from which a cognitive sumscore was calculated.
      The primary outcome was the change in cognitive sumscore between baseline and
      follow-up. Changes in cognitive sumscore were compared between patients with an
      ipsilateral foetal-type and those with a normal posterior cerebral artery, as
      assessed with CT or MR angiography. RESULTS: Of 145 patients enrolled in ICSS at
      the centre during the study period, 98 had both angiography at baseline and
      neuropsychological examination at baseline and at 6-months follow-up. The
      cognitive sum score decreased by 0.28 (95% confidence interval, 0.10 to 0.45) in
      13 patients with an ipsilateral foetal-type posterior cerebral artery and by 0.07
      (95% CI, 0.002 to 0.15) in 85 patients with a normal posterior cerebral artery
      (mean difference, -0.20; 95% CI, -0.40 to -0.01). This did not change essentially
      after adjustment for baseline factors. CONCLUSION: An ipsilateral foetal-type
      posterior cerebral artery appears to increase cognitive decline after carotid
      revascularisation. Our findings have to be reproduced in an independent study
      before further implications can be made.

PMID- 24739136
TI  - Aptamer-targeted DNA nanostructures for therapeutic delivery.
AB  - DNA-based nanostructures have been widely used in various applications due to
      their structural diversity, programmability, and uniform structures. Their
      intrinsic biocompatibility and biodegradability further motivates the
      investigation of DNA-based nanostructures as delivery vehicles. Incorporating
      AS1411 aptamers into DNA pyramids leads to enhanced intracellular uptake and
      selectively inhibits the growth of cancer cells, achieved without the use of
      transfection reagents. Furthermore, aptamer-displaying pyramids are found to be
      substantially more resistant to nuclease degradation than single-stranded
      aptamers. These findings, along with their modularity, reinforce the potential of
      DNA-based nanostructures for therapeutic applications. 

PMID- 24739137
TI  - A gain-of-function screen to identify genes that reduce lifespan in the adult of
      Drosophila melanogaster.
AB  - BACKGROUND: Several lines of evidence associate misregulated genetic expression
      with risk factors for diabetes, Alzheimer's, and other diseases that sporadically
      develop in healthy adults with no background of hereditary disorders. Thus, we
      are interested in genes that may be expressed normally through parts of an
      individual's life, but can cause physiological defects and disease when
      misexpressed in adulthood. RESULTS: We attempted to identify these genes in a
      model organism by arbitrarily misexpressing specific genes in adult Drosophila
      melanogaster, using 14,133 Gene Search lines. We identified 39 "reduced-lifespan
      genes" that, when misexpressed in adulthood, shortened the flies' lifespan to
      less than 30% of that of control flies. About half of these genes have human
      orthologs that are known to be involved in human diseases. For about one-fourth
      of the reduced-lifespan genes, suppressing apoptosis restored the lifespan
      shortened by their misexpression. We determined the organs responsible for
      reduced lifespan when these genes were misexpressed specifically in adulthood,
      and found that while some genes induced reduced lifespan only when misexpressed
      in specific adult organs, others could induce reduced lifespan when misexpressed
      in various organs. This finding suggests that tissue-specific dysfunction may be
      involved in reduced lifespan related to gene misexpression. Gene ontology
      analysis showed that reduced-lifespan genes are biased toward genes related to
      development. CONCLUSIONS: We identified 39 genes that, when misexpressed in
      adulthood, shortened the lifespan of adult flies. Suppressing apoptosis rescued
      this shortened lifespan for only a subset of the reduced-lifespan genes. The
      adult tissues in which gene misexpression caused early death differed among the
      reduced-lifespan genes. These results suggest that the cause of reduced lifespan
      upon misexpression differed among the genes.

PMID- 24739139
TI  - Introducing protein intrinsic disorder.

PMID- 24739138
TI  - Criteria for implementing interventions to reduce health inequalities in primary
      care settings in European regions.
AB  - BACKGROUND: The current social and political context is generating socio-economic
      inequalities between and within countries, causing and widening health
      inequalities. The development and implementation of interventions in primary
      health care (PHC) settings seem unavoidable. Attempts have been made to draw up
      adequate criteria to guide and evaluate interventions but none for the specific
      case of PHC. This methodological article aims to contribute to this field by
      developing and testing a set of criteria for guiding and evaluating real-life
      interventions to reduce health inequalities in PHC settings in European regions.
      METHODS: A literature review, nominal group technique, survey and evaluation
      template were used to design and test a set of criteria. The questionnaire was
      answered by professionals in charge of 46 interventions carried out in 12
      European countries, and collected detailed information about each intervention.
      Third-party experts scored the interventions using the set of evaluation criteria
      proposed. RESULTS: Nine criteria to guide and evaluate interventions were
      proposed: relevance, appropriateness, applicability, innovation, quality
      assurance, adequacy of resources, effectiveness in the process, effectiveness in
      results and mainstreaming. A working definition was drawn up for each one. These
      criteria were then used to evaluate the interventions identified. CONCLUSIONS:
      The set of criteria drawn up to guide the design, implementation and evaluation
      of interventions to reduce health inequalities in PHC will be a useful instrument
      to be applied to interventions under development for culturally, politically and
      socio-economically diverse PHC contexts throughout Europe.

PMID- 24739140
TI  - Effect of mobile phone use on salivary concentrations of protein, amylase,
      lipase, immunoglobulin A, lysozyme, lactoferrin, peroxidase and C-reactive
      protein of the parotid gland.
AB  - BACKGROUND: The possibility of side effects associated with the electromagnetic
      waves emitted from mobile phones is a controversial issue. The present study
      aimed to evaluate the effect of mobile phone use on parotid gland salivary
      concentrations of protein, amylase, lipase, immunoglobulin A, lysozyme,
      lactoferrin, peroxidase and C-reactive protein. METHODS: Stimulated salivary
      samples were collected simultaneously from both parotid glands of 86 healthy
      volunteers. Salivary flow rate and salivary concentrations of proteins, amylase,
      lipase, lysozyme, lactoferrin, peroxidase, C-reactive protein and immunoglobulin
      A, were measured. Data were analysed using t-tests and one-way analyses of
      variance. RESULTS: Salivary flow rate and parotid gland salivary concentrations
      of protein were significantly higher on the right side compared to the left in
      those that predominantly held mobile phones on the right side. In addition, there
      was a decrease in concentrations of amylase, lipase, lysozyme, lactoferrin and
      peroxidase. CONCLUSION: The side of dominant mobile phone use was associated with
      differences in salivary flow rate and parotid gland salivary concentrations, in
      right-dominant users. Although mobile phone use influenced salivary composition,
      the relationship was not significant.

PMID- 24739141
TI  - Effects associated with on- and off-label stimulant treatment of core autism and
      ADHD symptoms exhibited by children with autism spectrum disorder.
AB  - OBJECTIVE: Families of children with autism spectrum disorder are barraged by
      different treatment options. Some of these options have the support of empirical
      evidence while others do not. Stimulant treatments are typically utilized to
      treat symptoms of ADHD indicating an on-label use of such treatment. METHODS:
      This study examines the association of stimulant treatment with the on- (symptoms
      of ADHD) and off- (symptoms of ASD) label symptoms among children with ASD via a
      non-clinical, population-based sample. RESULTS: Results indicate no significant
      association of stimulant treatment with a reduction of on- or off-label symptoms
      among children with ASD. CONCLUSION: Stimulant medications utilized in the
      treatment of DSM core symptoms of autism spectrum disorder would be considered an
      off-label use because there is limited evidence to support that stimulants are
      effective in treating core symptoms of ASD, which is supported by the results of
      the current study.

PMID- 24739142
TI  - Critical role of TNF-alpha in cerebral aneurysm formation and progression to
      rupture.
AB  - BACKGROUND: Alterations in TNF-alpha expression have been associated with
      cerebral aneurysms, but a direct role in formation, progression, and rupture has
      not been established. METHODS: Cerebral aneurysms were induced through
      hypertension and a single stereotactic injection of elastase into the basal
      cistern in mice. To test the role of TNF-alpha in aneurysm formation, aneurysms
      were induced in TNF-alpha knockout mice and mice pretreated with the synthesized
      TNF-alpha inhibitor 3,6'dithiothalidomide (DTH). To assess the role of TNF-alpha
      in aneurysm progression and rupture, DTH was started 6 days after aneurysm
      induction. TNF-alpha expression was assessed through real-time PCR and
      immunofluorescence staining. RESULTS: TNF-alpha knockout mice and those pre
      treated with DTH had significantly decreased incidence of aneurysm formation and
      rupture as compared to sham mice. As compared with sham mice, TNF-alpha protein
      and mRNA expression was not significantly different in TNF-alpha knockout mice or
      those pre-treated with DTH, but was elevated in unruptured and furthermore in
      ruptured aneurysms. Subarachnoid hemorrhage (SAH) occurred between 7 and 21 days
      following aneurysm induction. To ensure aneurysm formation preceded rupture,
      additional mice underwent induction and sacrifice after 7 days. Seventy-five
      percent had aneurysm formation without evidence of SAH. Initiation of DTH
      treatment 6 days after aneurysm induction did not alter the incidence of aneurysm
      formation, but resulted in aneurysmal stabilization and a significant decrease in
      rupture. CONCLUSIONS: These data suggest a critical role of TNF-alpha in the
      formation and rupture of aneurysms in a model of cerebral aneurysm formation.
      Inhibitors of TNF-alpha could be beneficial in preventing aneurysmal progression
      and rupture.

PMID- 24739143
TI  - Seforta, an integrated tool for detecting the signature of selection in coding
      sequences.
AB  - BACKGROUND: The majority of amino acid residues are encoded by more than one
      codon, and a bias in the usage of such synonymous codons has been repeatedly
      demonstrated. One assumption is that this phenomenon has evolved to improve the
      efficiency of translation by reducing the time required for the recruitment of
      isoacceptors. The most abundant tRNA species are preferred at sites on the
      protein which are key for its functionality, a behavior which has been termed
      "translational accuracy". Although observed in many species, as yet no public
      domain software has been made available for its quantification. FINDINGS: We
      present here Seforta (Selection for Translational Accuracy), a program designed
      to quantify translational accuracy. It searches for synonymous codon usage bias
      in both conserved and non-conserved regions of coding sequences and computes a
      cumulative odds ratio and a Z-score. The specification of a set of preferred
      codons is desirable, but the program can also generate these. Finally, a
      randomization protocol calculates the probability that preferred codon
      combinations could have arisen by chance. CONCLUSIONS: Seforta is the first
      public domain program able to quantify translational accuracy. It comes with a
      simple graphical user interface and can be readily installed and adjusted to the
      user's requirements.

PMID- 24739144
TI  - Effect of electroacupuncture stimulation at Zusanli acupoint (ST36) on gastric
      motility: possible through PKC and MAPK signal transduction pathways.
AB  - BACKGROUND: Electroacupuncture (EA) stimulation has been shown to have a great
      therapeutic potential for treating gastrointestinal motility disorders. However,
      no evidence has clarified the mechanisms contributing to the effects of EA
      stimulation at the Zusanli acupoint (ST.36). This study was designed to
      investigate the regulative effect of EA stimulation at the ST.36 on gastric
      motility and to explore its possible mechanisms. METHODS: Thirty Sprague-Dawley
      rats were randomly divided into three groups: the ST.36 group, the non-acupoint
      group, and the control group. EA stimulation was set at 2 Hz, continuous mode,
      and 1 V for 30 min. The frequency and average peak amplitude of gastric motility
      were measured by electrogastrography. The protein kinase C (PKC) and mitogen
      activated protein kinase (MAPK) signaling pathways were assessed using real-time
      polymerase chain reactions. Caldesmon (CaD) and calponin (CaP) protein expression
      in the gastric antrum were detected on Western blots. A Computed Video Processing
      System was used to evaluate morphological changes in smooth muscle cells (SMCs)
      from the gastric antrum. RESULTS: EA stimulation at ST.36 had a dual effect on
      the frequency and average peak amplitude. Additionally, EA stimulation at ST.36
      regulated the expression of some genes in the PKC and MAPK signaling pathways,
      and it regulated the expression of the CaD and CaP proteins. EA serum induced SMC
      contractility. Promotion of gastric motility may correlate with up-regulation of
      MAPK6 (ERK3), MAPK13, and Prostaglandin-endoperoxide synthase 2 (PTGS2) gene
      expression, and the down-regulation of the collagen, type I, alpha 1 (COL1A1)
      gene and CaD and CaP protein expression. Inhibition of gastric motility may
      correlate with down-regulation of the Interleukin-1 receptor type 2 (IL1R2) and
      Matrix metalloproteinase-9 (MMP9) genes, and up-regulation of CaD and CaP protein
      expression. CONCLUSIONS: EA stimulation at ST.36 regulated gastric motility, and
      the effects were both promoting and inhibiting in rats. The possible mechanisms
      may correlate with the PKC and MAPK signal transduction pathways.

PMID- 24739145
TI  - On-site or off-site treatment of medical waste: a challenge.
AB  - Treating hazardous-infectious medical waste can be carried out on-site or off
      site of health-care establishments. Nevertheless, the selection between on-site
      and off-site locations for treating medical waste sometimes is a controversial
      subject. Currently in Iran, due to policies of Health Ministry, the hospitals
      have selected on-site-treating method as the preferred treatment. The objectives
      of this study were to assess the current condition of on-site medical waste
      treatment facilities, compare on-site medical waste treatment facilities with off
      site systems and find the best location of medical waste treatment. To assess the
      current on-site facilities, four provinces (and 40 active hospitals) were
      selected to participate in the survey. For comparison of on-site and off-site
      facilities (due to non availability of an installed off-site facility) Analytical
      Hierarchy Process (AHP) was employed. The result indicated that most on-site
      medical waste treating systems have problems in financing, planning, determining
      capacity of installations, operation and maintenance. AHP synthesis (with
      inconsistency ratio of 0.01 < 0.1) revealed that, in total, the off-site
      treatment of medical waste was in much higher priority than the on-site treatment
      (64.1% versus 35.9%). According to the results of study it was concluded that the
      off-site central treatment can be considered as an alternative. An amendment
      could be made to Iran's current medical waste regulations to have infectious
      hazardous waste sent to a central off-site installation for treatment. To begin
      and test this plan and also receive the official approval, a central off-site can
      be put into practice, at least as a pilot in one province. Next, if it was
      practically successful, it could be expanded to other provinces and cities. 

PMID- 24739146
TI  - The Balkan region: NDM-1-producing Klebsiella pneumoniae ST11 clonal strain
      causing outbreaks in Greece.
AB  - OBJECTIVES: Despite the fact that the NDM-1 carbapenemase has successfully
      disseminated worldwide, outbreaks remain uncommon in the European region. We
      describe the characteristics of the first outbreaks caused by NDM-1-producing
      Klebsiella pneumoniae clonal isolates in Greece. METHODS: Between January 2010
      and June 2013, 132 non-repetitive carbapenem-resistant Enterobacteriaceae
      isolates, which gave a positive modified Hodge test and were phenotypically
      suspected of metallo-beta-lactamase production, were recovered from patients
      hospitalized at Ioannina University Hospital. Resistance genes were identified by
      PCR and sequencing. Plasmid profiling, conjugation experiments, enterobacterial
      repetitive intergenic consensus PCR, PFGE and multilocus sequence typing (MLST)
      were performed. Patient records were retrieved to access patterns of acquisition.
      RESULTS: Molecular testing verified the presence in 78 K. pneumoniae isolates,
      collected from 71 patients, of the blaNDM-1 gene. The blaCTX-M-15, blaOXA-1 and
      blaTEM-1 genes were also present in most isolates. The blaNDM-1 gene was located
      on a narrow host range IncFII-type plasmid, of ~95 kb, flanked upstream by a non
      truncated ISAba125 element and downstream by the bleMBL gene. Genotyping
      clustered all K. pneumoniae isolates into a single clonal type with one subtype
      and MLST assigned them to sequence type 11. Two outbreaks were noted, the first
      between November and December 2011 involving four patients and the second
      initiated in May 2012 and ongoing, involving the remaining patients. All but two
      cases were characterized as hospital acquired. No links to immigration or travel
      history to endemic areas were established. CONCLUSIONS: This survey highlights
      the successful undetected dissemination of yet another carbapenemase in Greece
      and strengthens the hypothesis of a latent NDM-1 cluster in the Balkan region.

PMID- 24739147
TI  - Temporal trends in the discontinuation of first-line antiretroviral therapy.
AB  - OBJECTIVES: The aim of this study was to describe the rates and predictors of
      discontinuing first-line antiretroviral therapy in the different eras of
      treatment over a nearly 20 year period initiated in British Columbia between 1992
      and 2010. METHODS: All naive adults who started antiretroviral therapy (first
      line antiretroviral therapy) at any hospital or clinic in British Columbia
      (Canada) in 1992-2010 were included in this population-based retrospective cohort
      study. We were primarily interested in whether the era of treatment (1992-95,
      1996-2000, 2001-05 and 2006-10) was associated with discontinuation (stopping or
      switching of initial treatment) within 3 years of starting therapy. Weibull
      survival analysis was used to model the era of treatment and its association with
      time to discontinuation. RESULTS: The study included 7901 patients. Overall, the
      probability of discontinuing at 12, 24 and 36 months of treatment was 52%, 68%
      and 76%, respectively. In the adjusted model, variables associated with
      discontinuing were earlier treatment era, younger age, low adherence and lower
      baseline CD4 count. Regarding the 2006-10 period, the probability of
      discontinuing at 12, 24 and 36 months was 36%, 47% and 53%, respectively. In the
      adjusted model, the variables associated with discontinuation were younger age,
      female gender, AIDS-defining illnesses at baseline, low adherence and a protease
      inhibitor (PI)-based regimen. CONCLUSIONS: Discontinuation rates of first-line
      therapy have decreased over time, but are still quite high even for the latest
      drug combinations. In the most recent era, younger women on a PI regimen and
      those not achieving optimal adherence had the highest risk of discontinuing first
      line antiretroviral therapy.

PMID- 24739148
TI  - Dph7 catalyzes a previously unknown demethylation step in diphthamide
      biosynthesis.
AB  - Present on archaeal and eukaryotic translation elongation factor 2, diphthamide
      represents one of the most intriguing post-translational modifications on
      proteins. The biosynthesis of diphthamide was proposed to occur in three steps
      requiring seven proteins, Dph1-7, in eukaryotes. The functional assignments of
      Dph1-5 in the first and second step have been well established. Recent studies
      suggest that Dph6 (yeast YLR143W or human ATPBD4) and Dph7 (yeast YBR246W or
      human WDR85) are involved in the last amidation step, with Dph6 being the actual
      diphthamide synthetase catalyzing the ATP-dependent amidation reaction. However,
      the exact molecular role of Dph7 is unclear. Here we demonstrate that Dph7 is an
      enzyme catalyzing a previously unknown step in the diphthamide biosynthesis
      pathway. This step is between the Dph5- and Dph6-catalyzed reactions. We
      demonstrate that the Dph5-catalyzed reaction generates methylated diphthine, a
      previously overlooked intermediate, and Dph7 is a methylesterase that hydrolyzes
      methylated diphthine to produce diphthine and allows the Dph6-catalyzed amidation
      reaction to occur. Thus, our study characterizes the molecular function of Dph7
      for the first time and provides a revised diphthamide biosynthesis pathway. 

PMID- 24739149
TI  - Effects of minimally invasive procedures for evacuation of intracerebral hematoma
      in early stages on MMP-9 and BBB permeability in rabbits.
AB  - BACKGROUND: The effects of performing a minimally invasive procedure at different
      stages after intracerebral hemorrhage on perihematomal MMP-9 expression and blood
      brain barrier (BBB) permeability were evaluated. METHODS: Sixty rabbits were
      randomly distributed into a model control group (MC group, 30 rabbits) or a
      minimally invasive group (MI group, 30 rabbits). A model of intracerebral
      hemorrhage was established in the MC and MI group. In the MI group, the
      intracerebral hematoma was evacuated by stereotactic minimally invasive
      procedures over 6 hours (6 rabbits), 12 hours (6 rabbits), 18 hours (6 rabbits)
      24 hours or 48 hours (6 rabbits) following successful induction of intracerebral
      hemorrhage. The same procedure was performed in the MC group at the same time
      point but without evacuating the hematoma. All the animals were sacrificed within
      two weeks after the hematoma was surgically evacuated. A neurological deficit
      score was determined, and the perihematomal MMP-9 level and the BBB permeability
      were measured. RESULTS: The neurological deficit score, perihematomal MMP-9 level
      and BBB permeability of the MI group decreased significantly compared to the MC
      group. Performing the MI procedure 6-12 h after intracerebral hemorrhage showed
      the most favorable outcome. CONCLUSIONS: Regarding the pathophysiological changes
      surrounding the hematoma, the optimal time window of performing MI procedures for
      the intracerebral hematoma evacuation might be within 6-12 h after hemorrhage.

PMID- 24739150
TI  - Shedding light on conformational dynamics of na(+)-coupled transporters.

PMID- 24739151
TI  - Nanoscopic injury with macroscopic consequences: tau proteins as mediators of
      diffuse axonal injury.

PMID- 24739152
TI  - Unknown unknowns: the challenge of systematic and statistical error in molecular
      dynamics simulations.

PMID- 24739153
TI  - Drifting through the beehive.

PMID- 24739154
TI  - The importance of intrinsic order in a disordered protein ligand.

PMID- 24739155
TI  - Membrane protein structural validation by oriented sample solid-state NMR:
      diacylglycerol kinase.
AB  - The validation of protein structures through functional assays has been the norm
      for many years. Functional assays perform this validation for water-soluble
      proteins very well, but they need to be performed in the same environment as that
      used for the structural analysis. This is difficult for membrane proteins that
      are often structurally characterized in detergent environments, although
      functional assays for these proteins are most frequently performed in lipid
      bilayers. Because the structure of membrane proteins is known to be sensitive to
      the membrane mimetic environment, such functional assays are appropriate for
      validating the protein construct, but not the membrane protein structure. Here,
      we compare oriented sample solid-state NMR spectral data of diacylglycerol kinase
      previously published with predictions of such data from recent structures of this
      protein. A solution NMR structure of diacylglycerol kinase has been obtained in
      detergent micelles and three crystal structures have been obtained in a monoolein
      cubic phase. All of the structures are trimeric with each monomer having three
      transmembrane and one amphipathic helices. However, the solution NMR structure
      shows typical perturbations induced by a micelle environment that is reflected in
      the predicted solid-state NMR resonances from the structural coordinates. The
      crystal structures show few such perturbations, especially for the wild-type
      structure and especially for the monomers that do not have significant crystal
      contacts. For these monomers the predicted and observed data are nearly
      identical. The thermostabilized constructs do show more perturbations, especially
      the A41C mutation that introduces a hydrophilic residue into what would be the
      middle of the lipid bilayer inducing additional hydrogen bonding between trimers.
      These results demonstrate a general technique for validating membrane protein
      structures with minimal data obtained from membrane proteins in liquid
      crystalline lipid bilayers by oriented sample solid-state NMR. 

PMID- 24739156
TI  - Exciting cell membranes with a blustering heat shock.
AB  - Brief heat shocks delivered to cells by pulsed laser light can evoke action
      potentials in neurons and contraction in cardiomyocytes, but the primary
      biophysical mechanism has been elusive. In this report we show in the
      neuromuscular junction of Caenorhabditis elegans that application of a 500
      degrees C/s heat shock for 500 MUs evoked ~35 pA of excitatory current and
      injected ~23 fC(femtocoulomb) of charge into the cell while raising the
      temperature only 0.25 degrees C. The key variable driving the current was the
      rate of change of temperature (dT/dt heat shock), not temperature itself. The
      photothermal heat shock current was voltage-dependent and was from thermally
      driven displacement of ions near the plasma membrane. The charge movement was
      rapid during the heat shock and slow during thermal relaxation, thus leading to
      an asymmetrical capacitive current that briefly depolarized the cell. A simple
      quantitative model is introduced to describe modulation of the membrane potential
      and facilitate practical application of optical heat shock stimuli.

PMID- 24739157
TI  - Measuring microtubule polarity in spindles with second-harmonic generation.
AB  - The spatial organization of microtubule polarity, and the interplay between
      microtubule polarity and protein localization, is thought to be crucial for
      spindle assembly, anaphase, and cytokinesis, but these phenomena remain poorly
      understood, in part due to the difficulty of measuring microtubule polarity in
      spindles. We develop and implement a method to nonperturbatively and
      quantitatively measure microtubule polarity throughout spindles using a
      combination of second-harmonic generation and two-photon fluorescence. We
      validate this method using computer simulations and by comparison to structural
      data on spindles obtained from electron tomography and laser ablation. This
      method should provide a powerful tool for studying spindle organization and
      function, and may be applicable for investigating microtubule polarity in other
      systems.

PMID- 24739158
TI  - Fast label-free cytoskeletal network imaging in living mammalian cells.
AB  - We present a full-field technique that allows label-free cytoskeletal network
      imaging inside living cells. This noninvasive technique allows monitoring of the
      cytoskeleton dynamics as well as interactions between the latter and organelles
      on any timescale. It is based on high-resolution quantitative phase imaging
      (modified Quadriwave lateral shearing interferometry) and can be directly
      implemented using any optical microscope without modification. We demonstrate the
      capability of our setup on fixed and living Chinese hamster ovary cells, showing
      the cytoskeleton dynamics in lamellipodia during protrusion and mitochondria
      displacement along the cytoskeletal network. In addition, using the quantitative
      function of the technique, along with simulation tools, we determined the
      refractive index of a single tubulin microtubule to be ntubu=2.36+/-0.6 at
      lambda=527 nm. 

PMID- 24739159
TI  - Force generation by endocytic actin patches in budding yeast.
AB  - Membrane deformation during endocytosis in yeast is driven by local, templated
      assembly of a sequence of proteins including polymerized actin and curvature
      generating coat proteins such as clathrin. Actin polymerization is required for
      successful endocytosis, but it is not known by what mechanisms actin
      polymerization generates the required pulling forces. To address this issue, we
      develop a simulation method in which the actin network at the protein patch is
      modeled as an active gel. The deformation of the gel is treated using a finite
      element approach. We explore the effects and interplay of three different types
      of force driving invagination: 1), forces perpendicular to the membrane,
      generated by differences between actin polymerization rates at the edge of the
      patch and those at the center; 2), the inherent curvature of the coat-protein
      layer; and 3), forces parallel to the membrane that buckle the coat protein
      layer, generated by an actomyosin contractile ring. We find that with optimistic
      estimates for the stall stress of actin gel growth and the shear modulus of the
      actin gel, actin polymerization can generate almost enough force to overcome the
      turgor pressure. In combination with the other mechanisms, actin polymerization
      can the force over the critical value.

PMID- 24739160
TI  - Role of a helix B lysine residue in the photoactive site in channelrhodopsins.
AB  - In most studied microbial rhodopsins two conserved carboxylic acid residues (the
      homologs of Asp-85 and Asp-212 in bacteriorhodopsin) and an arginine residue (the
      homolog of Arg-82) form a complex counterion to the protonated retinylidene
      Schiff base, and neutralization of the negatively charged carboxylates causes red
      shifts of the absorption maximum. In contrast, the corresponding neutralizing
      mutations in some relatively low-efficiency channelrhodopsins (ChRs) result in
      blue shifts. These ChRs do not contain a lysine residue in the second helix,
      conserved in higher efficiency ChRs (Lys-132 in the crystallized ChR chimera). By
      action spectroscopy of photoinduced channel currents in HEK293 cells and
      absorption spectroscopy of detergent-purified pigments, we found that in tested
      ChRs the Lys-132 homolog controls the direction of spectral shifts in the mutants
      of the photoactive site carboxylic acid residues. Analysis of double mutants
      shows that red spectral shifts occur when this Lys is present, whether naturally
      or by mutagenesis, and blue shifts occur when it is replaced with a neutral
      residue. A neutralizing mutation of the Lys-132 homolog alone caused a red
      spectral shift in high-efficiency ChRs, whereas its introduction into low
      efficiency ChR1 from Chlamydomonas augustae (CaChR1) caused a blue shift. Taking
      into account that the effective charge of the carboxylic acid residues is a key
      factor in microbial rhodopsin spectral tuning, these findings suggest that the
      Lys-132 homolog modulates their pKa values. On the other hand, mutation of the
      Arg-82 homolog that fulfills this role in bacteriorhodopsin caused minimal
      spectral changes in the tested ChRs. Titration revealed that the pKa of the Asp
      85 homolog in CaChR1 lies in the alkaline region unlike in most studied microbial
      rhodopsins, but is substantially decreased by introduction of a Lys-132 homolog
      or neutralizing mutation of the Asp-212 homolog. In the three ChRs tested the Lys
      132 homolog also alters channel current kinetics. 

PMID- 24739161
TI  - Correlating charge movements with local conformational changes of a Na(+)-coupled
      cotransporter.
AB  - To gain insight into the steady-state and dynamic characteristics of structural
      rearrangements of an electrogenic secondary-active cotransporter during its
      transport cycle, two measures of conformational change (pre-steady-state current
      relaxations and intensity of fluorescence emitted from reporter fluorophores)
      were investigated as a function of membrane potential and external substrate.
      Cysteines were substituted at three believed-new sites in the type IIb Na(+)
      coupled inorganic phosphate cotransporter (SLC34A2 flounder isoform) that were
      predicted to be involved in conformational changes. Labeling at one site resulted
      in substantial suppression of transport activity, whereas for the other sites,
      function remained comparable to the wild-type. For these mutants, the properties
      of the pre-steady-state charge relaxations were similar for each, whereas
      fluorescence intensity changes differed significantly. Fluorescence changes could
      be accounted for by simulations using a five-state model with a unique set of
      apparent fluorescence intensities assigned to each state according to the site of
      labeling. Fluorescence reported from one site was associated with inward and
      outward conformations, whereas for the other sites, including four previously
      indentified sites, emissions were associated principally with one or the other
      orientation of the transporter. The same membrane potential change induced
      complementary changes in fluorescence at some sites, which suggested that the
      microenvironments of the respective fluorophores experience concomitant changes
      in polarity. In response to step changes in voltage, the pre-steady-state current
      relaxation and the time course of change in fluorescence intensity were described
      by single exponentials. For one mutant the time constants matched well with and
      without external Na(+), providing direct evidence that this label reports
      conformational changes accompanying intrinsic charge movement and cation
      interactions. 

PMID- 24739162
TI  - Imaging the lipid-phase-dependent pore formation of equinatoxin II in droplet
      interface bilayers.
AB  - Using phase-separated droplet interface bilayers, we observe membrane binding and
      pore formation of a eukaryotic cytolysin, Equinatoxin II (EqtII). EqtII activity
      is known to depend on the presence of sphingomyelin in the target membrane and is
      enhanced by lipid phase separation. By imaging the ionic flux through individual
      pores in vitro, we observe that EqtII pores form predominantly within the liquid
      disordered phase. We observe preferential binding of labeled EqtII at liquid
      ordered/liquid-disordered domain boundaries before it accumulates in the liquid
      disordered phase.

PMID- 24739163
TI  - A critical evaluation of in silico methods for detection of membrane protein
      intrinsic disorder.
AB  - Intrinsically disordered regions in proteins possess important biological roles
      including transcriptional regulation, molecular recognition, and provision of
      sites for posttranslational modification. In three-dimensional crystallization of
      both soluble and membrane proteins, identification and removal of disordered
      regions is often necessary for obtaining crystals possessing sufficient long
      range order for structure determination. Disordered regions can be identified
      experimentally, with techniques such as limited proteolysis coupled with mass
      spectrometry, or computationally, by using disorder prediction programs, of which
      many are available. Although these programs use various methods to predict
      disorder from a protein's primary sequence, they all were developed using
      information derived from soluble protein structures. Therefore, their performance
      and accuracy when applied to integral membrane proteins remained an open
      question. We evaluated the performance of 13 disorder prediction programs on a
      dataset containing 343 membrane proteins, and upon subdatasets containing only
      alpha-helical or beta-barrel proteins. These programs were ranked using multiple
      metrics, including metrics specifically created for membrane proteins. Analysis
      of these data shows a clear distinction between programs that accurately predict
      disordered regions in membrane proteins and programs which perform poorly, and
      allows for the robust integration of in silico disorder prediction into our
      PSI:Biology membrane protein structural genomics pipeline.

PMID- 24739164
TI  - Shaped apertures in photoresist films enhance the lifetime and mechanical
      stability of suspended lipid bilayers.
AB  - Planar lipid bilayers suspended in apertures provide a controlled environment for
      ion channel studies. However, short lifetimes and poor mechanical stability of
      suspended bilayers limit the experimental throughput of bilayer electrophysiology
      experiments. Although bilayers are more stable in smaller apertures, ion channel
      incorporation through vesicle fusion with the suspended bilayer becomes
      increasingly difficult. In an alternative bilayer stabilization approach, we have
      developed shaped apertures in SU8 photoresist that have tapered sidewalls and a
      minimum diameter between 60 and 100 MUm. Bilayers formed at the thin tip of these
      shaped apertures, either with the painting or the folding method, display
      drastically increased lifetimes, typically >20 h, and mechanical stability, being
      able to withstand extensive perturbation of the buffer solution. Single-channel
      electrical recordings of the peptide alamethicin and of the proteoliposome
      delivered potassium channel KcsA demonstrate channel conductance with low noise,
      made possible by the small capacitance of the 50 MUm thick SU8 septum, which is
      only thinned around the aperture, and unimpeded proteoliposome fusion, enabled by
      the large aperture diameter. We anticipate that these shaped apertures with
      micrometer edge thickness can substantially enhance the throughput of channel
      characterization by bilayer lipid membrane electrophysiology, especially in
      combination with automated parallel bilayer platforms. 

PMID- 24739165
TI  - Variation of the detergent-binding capacity and phospholipid content of membrane
      proteins when purified in different detergents.
AB  - Purified membrane proteins are ternary complexes consisting of protein, lipid,
      and detergent. Information about the amounts of detergent and endogenous
      phospholipid molecules bound to purified membrane proteins is largely lacking. In
      this systematic study, three model membrane proteins of different oligomeric
      states were purified in nine different detergents at commonly used concentrations
      and characterized biochemically and biophysically. Detergent-binding capacities
      and phospholipid contents of the model proteins were determined and compared. The
      insights on ternary complexes obtained from the experimental results, when put
      into a general context, are summarized as follows. 1), The amount of detergent
      and 2) the amount of endogenous phospholipids bound to purified membrane proteins
      are dependent on the size of the hydrophobic lipid-accessible protein surface
      areas and the physicochemical properties of the detergents used. 3), The size of
      the detergent and lipid belt surrounding the hydrophobic lipid-accessible surface
      of purified membrane proteins can be tuned by the appropriate choice of
      detergent. 4), The detergents n-nonyl-beta-D-glucopyranoside and Cymal-5 have
      exceptional delipidating effects on ternary complexes. 5), The types of
      endogenous phospholipids bound to membrane proteins can vary depending on the
      detergent used for solubilization and purification. 6), Furthermore, we
      demonstrate that size-exclusion chromatography can be a suitable method for
      estimating the molecular mass of ternary complexes. The findings presented
      suggest a strategy to control and tune the numbers of detergent and endogenous
      phospholipid molecules bound to membrane proteins. These two parameters are
      potentially important for the successul crystallization of membrane proteins for
      structure determination by crystallographic approaches. 

PMID- 24739166
TI  - Zebrafish cardiac muscle thick filaments: isolation technique and three
      dimensional structure.
AB  - To understand how mutations in thick filament proteins such as cardiac myosin
      binding protein-C or titin, cause familial hypertrophic cardiomyopathies, it is
      important to determine the structure of the cardiac thick filament. Techniques
      for the genetic manipulation of the zebrafish are well established and it has
      become a major model for the study of the cardiovascular system. Our goal is to
      develop zebrafish as an alternative system to the mammalian heart model for the
      study of the structure of the cardiac thick filaments and the proteins that form
      it. We have successfully isolated thick filaments from zebrafish cardiac muscle,
      using a procedure similar to those for mammalian heart, and analyzed their
      structure by negative-staining and electron microscopy. The isolated filaments
      appear well ordered with the characteristic 42.9 nm quasi-helical repeat of the
      myosin heads expected from x-ray diffraction. We have performed single particle
      image analysis on the collected electron microscopy images for the C-zone region
      of these filaments and obtained a three-dimensional reconstruction at 3.5 nm
      resolution. This reconstruction reveals structure similar to the mammalian thick
      filament, and demonstrates that zebrafish may provide a useful model for the
      study of the changes in the cardiac thick filament associated with disease
      processes.

PMID- 24739167
TI  - Binding and channeling of alternative substrates in the enzyme DmpFG: a molecular
      dynamics study.
AB  - DmpFG is a bifunctional enzyme comprised of an aldolase subunit, DmpG, and a
      dehydrogenase subunit, DmpF. The aldehyde intermediate produced by the aldolase
      is channeled directly through a buried molecular channel in the protein structure
      from the aldolase to the dehydrogenase active site. In this study, we have
      investigated the binding of a series of progressively larger substrates to the
      aldolase, DmpG, using molecular dynamics. All substrates investigated are easily
      accommodated within the active site, binding with free energy values comparable
      to the physiological substrate 4-hydroxy-2-ketovalerate. Subsequently, umbrella
      sampling was utilized to obtain free energy surfaces for the aldehyde
      intermediates (which would be generated from the aldolase reaction on each of
      these substrates) to move through the channel to the dehydrogenase DmpF. Small
      substrates were channeled with limited barriers in an energetically feasible
      process. We show that the barriers preventing bulky intermediates such as
      benzaldehyde from moving through the wild-type protein can be removed by
      selective mutation of channel-lining residues, demonstrating the potential for
      tailoring this enzyme to allow its use for the synthesis of specific chemical
      products. Furthermore, positions of transient escape routes in this flexible
      channel were determined. 

PMID- 24739168
TI  - Kinesin's neck-linker determines its ability to navigate obstacles on the
      microtubule surface.
AB  - The neck-linker is a structurally conserved region among most members of the
      kinesin superfamily of molecular motor proteins that is critical for kinesin's
      processive transport of intracellular cargo along the microtubule surface.
      Variation in the neck-linker length has been shown to directly modulate
      processivity in different kinesin families; for example, kinesin-1, with a
      shorter neck-linker, is more processive than kinesin-2. Although small
      differences in processivity are likely obscured in vivo by the coupling of most
      cargo to multiple motors, longer and more flexible neck-linkers may allow
      different kinesins to navigate more efficiently around the many obstacles,
      including microtubule-associated proteins (MAPs), that are found on the
      microtubule surface within cells. We hypothesize that, due to its longer neck
      linker, kinesin-2 can more easily navigate obstacles (e.g., MAPs) on the
      microtubule surface than kinesin-1. We used total internal reflection
      fluorescence microscopy to observe single-molecule motility from different
      kinesin-1 and kinesin-2 neck-linker chimeras stepping along microtubules in the
      absence or presence of two Tau isoforms, 3RS-Tau and 4RL-Tau, both of which are
      MAPs that are known to differentially affect kinesin-1 motility. Our results
      demonstrate that unlike kinesin-1, kinesin-2 is insensitive to the presence of
      either Tau isoform, and appears to have the ability to switch protofilaments
      while stepping along the microtubule when challenged by an obstacle, such as Tau.
      Thus, although kinesin-1 may be more processive, the longer neck-linker length of
      kinesin-2 allows it to be better optimized to navigate the complex microtubule
      landscape. These results provide new insight, to our knowledge, into how kinesin
      1 and kinesin-2 may work together for the efficient delivery of cargo in cells.

PMID- 24739169
TI  - Water-peptide site-specific interactions: a structural study on the hydration of
      glutathione.
AB  - Water-peptide interactions play an important role in determining peptide
      structure and function. Nevertheless, a microscopic description of these
      interactions is still incomplete. In this study we have investigated at the
      atomic scale length the interaction between water and the tripeptide glutathione.
      The rationale behind this work, based on the combination between a neutron
      diffraction experiment and a computer simulation, is twofold. It extends previous
      studies on amino acids, addressing issues such as the perturbation of the water
      network brought by a larger biomolecule in solution. In addition, and more
      importantly, it seeks a possible link between the atomic length scale description
      of the glutathione-water interaction with the specific biological functionality
      of glutathione, an important intracellular antioxidant. Results indicate a rather
      weak hydrogen bond between the thiol (-SH) group of cysteine and its first
      neighbor water molecule. This -SH group serves as a proton donor, is responsible
      for the biological activity of glutathione, and it is involved in the formation
      of glutathione disulfide, the oxidized form of glutathione. Moreover, the
      hydration shell of the chemically identical carboxylate group on the glutamic
      acid residue and on the glycine residue shows an intriguing different spatial
      location of water molecules and coordination numbers around the two CO2(-)
      groups. 

PMID- 24739170
TI  - Nucleotide regulation of the structure and dynamics of G-actin.
AB  - Actin, a highly conserved cytoskeletal protein found in all eukaryotic cells,
      facilitates cell motility and membrane remodeling via a directional
      polymerization cycle referred to as treadmilling. The nucleotide bound at the
      core of each actin subunit regulates this process. Although the biochemical
      kinetics of treadmilling has been well characterized, the atomistic details of
      how the nucleotide affects polymerization remain to be definitively determined.
      There is increasing evidence that the nucleotide regulation (and other
      characteristics) of actin cannot be fully described from the minimum energy
      structure, but rather depends on a dynamic equilibrium between conformations. In
      this work we explore the conformational mobility of the actin monomer (G-actin)
      in a coarse-grained subspace using umbrella sampling to bias all-atom molecular
      dynamics simulations along the variables of interest. The results reveal that ADP
      bound actin subunits are more conformationally mobile than ATP-bound subunits. We
      used a multiscale analysis method involving coarse-grained and atomistic
      representations of these simulations to characterize how the nucleotide affects
      the low-energy states of these systems. The interface between subdomains SD2-SD4,
      which is important for polymerization, is stabilized in an actin filament-like (F
      actin) conformation in ATP-bound G-actin. Additionally, the nucleotide modulates
      the conformation of the SD1-SD3 interface, a region involved in the binding of
      several actin-binding proteins.

PMID- 24739171
TI  - Stable polyglutamine dimers can contain beta-hairpins with interdigitated side
      chains-but not alpha-helices, beta-nanotubes, beta-pseudohelices, or steric
      zippers.
AB  - A common thread connecting nine fatal neurodegenerative protein aggregation
      diseases is an abnormally expanded polyglutamine tract found in the respective
      proteins. Although the structure of this tract in the large mature aggregates is
      increasingly well described, its structure in the small early aggregates remains
      largely unknown. As experimental evidence suggests that the most toxic species
      along the aggregation pathway are the small early ones, developing strategies to
      alleviate disease pathology calls for understanding the structure of
      polyglutamine peptides in the early stages of aggregation. Here, we present a
      criterion, grounded in available experimental data, that allows for using kinetic
      stability of dimers to assess whether a given polyglutamine conformer can be on
      the aggregation path. We then demonstrate that this criterion can be assessed
      using present-day molecular dynamics simulations. We find that although the alpha
      helical conformer of polyglutamine is very stable, dimers of alpha-helices lack
      the kinetic stability necessary to support further oligomerization. Dimers of
      steric zipper, beta-nanotube, and beta-pseudohelix conformers are also too short
      lived to initiate aggregation. The beta-hairpin-containing conformers, instead,
      invariably form very stable dimers when their side chains are interdigitated.
      Combining these findings with the implications of recent solid-state NMR data on
      mature fibrils, we propose a possible pathway for the initial stages of
      polyglutamine aggregation, in which beta-hairpin-containing conformers act as
      templates for fibril formation. 

PMID- 24739172
TI  - The role of high-dimensional diffusive search, stabilization, and frustration in
      protein folding.
AB  - Proteins are polymeric molecules with many degrees of conformational freedom
      whose internal energetic interactions are typically screened to small distances.
      Therefore, in the high-dimensional conformation space of a protein, the energy
      landscape is locally relatively flat, in contrast to low-dimensional
      representations, where, because of the induced entropic contribution to the full
      free energy, it appears funnel-like. Proteins explore the conformation space by
      searching these flat subspaces to find a narrow energetic alley that we call a
      hypergutter and then explore the next, lower-dimensional, subspace. Such a
      framework provides an effective representation of the energy landscape and
      folding kinetics that does justice to the essential characteristic of high
      dimensionality of the search-space. It also illuminates the important role of
      nonnative interactions in defining folding pathways. This principle is here
      illustrated using a coarse-grained model of a family of three-helix bundle
      proteins whose conformations, once secondary structure has formed, can be defined
      by six rotational degrees of freedom. Two folding mechanisms are possible, one of
      which involves an intermediate. The stabilization of intermediate subspaces (or
      states in low-dimensional projection) in protein folding can either speed up or
      slow down the folding rate depending on the amount of native and nonnative
      contacts made in those subspaces. The folding rate increases due to reduced
      dimension pathways arising from the mere presence of intermediate states, but
      decreases if the contacts in the intermediate are very stable and introduce
      sizeable topological or energetic frustration that needs to be overcome.
      Remarkably, the hypergutter framework, although depending on just a few
      physically meaningful parameters, can reproduce all the types of experimentally
      observed curvature in chevron plots for realizations of this fold. 

PMID- 24739173
TI  - A parametrically constrained optimization method for fitting sedimentation
      velocity experiments.
AB  - A method for fitting sedimentation velocity experiments using whole boundary Lamm
      equation solutions is presented. The method, termed parametrically constrained
      spectrum analysis (PCSA), provides an optimized approach for simultaneously
      modeling heterogeneity in size and anisotropy of macromolecular mixtures. The
      solutions produced by PCSA are particularly useful for modeling polymerizing
      systems, where a single-valued relationship exists between the molar mass of the
      growing polymer chain and its corresponding anisotropy. The PCSA uses functional
      constraints to identify this relationship, and unlike other multidimensional grid
      methods, assures that only a single molar mass can be associated with a given
      anisotropy measurement. A description of the PCSA algorithm is presented, as well
      as several experimental and simulated examples that illustrate its utility and
      capabilities. The performance advantages of the PCSA method in comparison to
      other methods are documented. The method has been added to the UltraScan-III
      software suite, which is available for free download from
      http://www.ultrascan.uthscsa.edu. 

PMID- 24739174
TI  - Karyopherin-centric control of nuclear pores based on molecular occupancy and
      kinetic analysis of multivalent binding with FG nucleoporins.
AB  - Intrinsically disordered Phe-Gly nucleoporins (FG Nups) within nuclear pore
      complexes exert multivalent interactions with transport receptors (Karyopherins
      (Kaps)) that orchestrate nucleocytoplasmic transport. Current FG-centric views
      reason that selective Kap translocation is promoted by alterations in the barrier
      like FG Nup conformations. However, the strong binding of Kaps with the FG Nups
      due to avidity contradicts rapid Kap translocation in vivo. Here, using surface
      plasmon resonance, we innovate a means to correlate in situ mechanistic
      (molecular occupancy and conformational changes) with equilibrium (binding
      affinity) and kinetic (multivalent binding kinetics) aspects of Karyopherinbeta1
      (Kapbeta1) binding to four different FG Nups. A general feature of the FxFG
      domains of Nup214, Nup62, and Nup153 is their capacity to extend and accommodate
      large numbers of Kapbeta1 molecules at physiological Kapbeta1 concentrations. A
      notable exception is the GLFG domain of Nup98, which forms a partially penetrable
      cohesive layer. Interestingly, we find that a slowly exchanging Kapbeta1 phase
      forms an integral constituent within the FG Nups that coexists with a fast phase,
      which dominates transport kinetics due to limited binding with the pre-occupied
      FG Nups at physiological Kapbeta1 concentrations. Altogether, our data reveal an
      emergent Kap-centric barrier mechanism that may underlie mechanistic and kinetic
      control in the nuclear pore complex.

PMID- 24739175
TI  - Observation of small cluster formation in concentrated monoclonal antibody
      solutions and its implications to solution viscosity.
AB  - Monoclonal antibodies (mAbs) are a major class of biopharmaceuticals. It is
      hypothesized that some concentrated mAb solutions exhibit formation of a solution
      phase consisting of reversibly self-associated aggregates (or reversible
      clusters), which is speculated to be responsible for their distinct solution
      properties. Here, we report direct observation of reversible clusters in
      concentrated solutions of mAbs using neutron spin echo. Specifically, a stable
      mAb solution is studied across a transition from dispersed monomers in dilute
      solution to clustered states at more concentrated conditions, where clusters of a
      preferred size are observed. Once mAb clusters have formed, their size, in
      contrast to that observed in typical globular protein solutions, is observed to
      remain nearly constant over a wide range of concentrations. Our results not only
      conclusively establish a clear relationship between the undesirable high
      viscosity of some mAb solutions and the formation of reversible clusters with
      extended open structures, but also directly observe self-assembled mAb protein
      clusters of preferred small finite size similar to that in micelle formation that
      dominate the properties of concentrated mAb solutions. 

PMID- 24739177
TI  - A general functional response of cytotoxic T lymphocyte-mediated killing of
      target cells.
AB  - Cytotoxic T lymphocytes (CTLs) kill virus-infected cells and tumor cells, and
      play a critical role in immune protection. Our knowledge of how the CTL killing
      efficiency varies with CTL and target cell numbers is limited. Here, we simulate
      a region of lymphoid tissue using a cellular Potts model to characterize the
      functional response of CTL killing of target cells, and find that the total
      killing rate saturates both with the CTL and the target cell densities. The
      relative saturation in CTL and target cell densities is determined by whether a
      CTL can kill multiple target cells at the same time, and whether a target cell
      can be killed by many CTLs together. We find that all the studied regimes can be
      well described by a double-saturation (DS) function with two different saturation
      constants. We show that this DS model can be mechanistically derived for the
      cases where target cells are killed by a single CTL. For the other cases, a
      biological interpretation of the parameters is still possible. Our results imply
      that this DS function can be used as a tool to predict the cellular interactions
      in cytotoxicity data. 

PMID- 24739176
TI  - Conformational recognition of an intrinsically disordered protein.
AB  - There is a growing interest in understanding the properties of intrinsically
      disordered proteins (IDPs); however, the characterization of these states remains
      an open challenge. IDPs appear to have functional roles that diverge from those
      of folded proteins and revolve around their ability to act as hubs for protein
      protein interactions. To gain a better understanding of the modes of binding of
      IDPs, we combined statistical mechanics, calorimetry, and NMR spectroscopy to
      investigate the recognition and binding of a fragment from the disordered protein
      Gab2 by the growth factor receptor-bound protein 2 (Grb2), a key interaction for
      normal cell signaling and cancer development. Structural ensemble refinement by
      NMR chemical shifts, thermodynamics measurements, and analysis of point mutations
      indicated that the population of preexisting bound conformations in the free
      state ensemble of Gab2 is an essential determinant for recognition and binding by
      Grb2. A key role was found for transient polyproline II (PPII) structures and
      extended conformations. Our findings are likely to have very general implications
      for the biological behavior of IDPs in light of the evidence that a large
      fraction of these proteins possess a specific propensity to form PPII and to
      adopt conformations that are more extended than the typical random-coil states. 

PMID- 24739178
TI  - Involvement of miR-605 and miR-34a in the DNA damage response promotes apoptosis
      induction.
AB  - MicroRNAs are key regulators of gene expression at the posttranscriptional level.
      In this study, we focus on miR-605 and miR-34a, which are direct transcriptional
      targets of p53 and in turn enhance its tumor suppressor function by acting
      upstream and downstream of it, respectively. miR-605 promotes p53 activation by
      repressing the expression of mdm2, whereas miR-34a promotes p53-dependent
      apoptosis by suppressing the expression of antiapoptotic genes such as bcl-2.
      What roles they play in the p53-mediated DNA damage response is less well
      understood. Here, we develop a four-module model of the p53 network to
      investigate the effect of miR-605 and miR-34a on the cell-fate decision after
      ionizing radiation. Results of numerical simulation indicate that the cell fate
      is closely associated with network dynamics. The concentration of p53 undergoes
      few pulses in response to repairable DNA damage, or it first oscillates and then
      switches to high plateau levels after irreparable damage. The amplitude of p53
      pulses rises to various extents depending on miR-605 expression, and miR-605
      accelerates the switching behavior of p53 levels to induce apoptosis. In
      parallel, miR-34a promotes apoptosis by enhancing the accumulation of free
      p53AIP1, a key proapoptotic protein. Thus, both miR-605 and miR-34a can mediate
      cellular outcomes and the timing of apoptosis. Moreover, miR-605 and PTEN
      complement each other in elevating p53 levels to trigger apoptosis. Taken
      together, miR-605 and miR-34a cooperate to endow the network with a fail-safe
      mechanism for apoptosis induction. This computational study also enriches our
      understanding of the action modes of p53-targeted microRNAs. 

PMID- 24739179
TI  - Macromolecular crowding as a regulator of gene transcription.
AB  - Studies of macromolecular crowding have shown its important effects on molecular
      transport and interactions in living cells. Less clear is the effect of crowding
      when its influence is incorporated into a complex network of interactions. Here,
      we explore the effects of crowding in the cell nucleus on a model of gene
      transcription as a network of reactions involving transcription factors, RNA
      polymerases, and DNA binding sites for these proteins. The novelty of our
      approach is that we determine the effects of crowding on the rates of these
      reactions using Brownian dynamics and Monte Carlo simulations, allowing us to
      integrate molecular-scale information, such as the shapes and sizes of each
      molecular species, into the rate equations of the model. The steady-state
      cytoplasmic mRNA concentration shows several regimes with qualitatively different
      dependences on the volume fraction, phi, of crowding agents in the nucleus,
      including a broad range of parameter values where it depends nonmonotonically on
      phi, with maximum mRNA production occurring at a physiologically relevant value.
      The extent of this crowding dependence can be modulated by a variety of means,
      suggesting that the transcriptional output of a gene can be regulated jointly by
      the local level of macromolecular crowding in the nucleus, together with the
      local concentrations of polymerases and DNA-binding proteins, as well as other
      properties of the gene's physical environment. 

PMID- 24739180
TI  - Attraction of rotors to the pulmonary veins in paroxysmal atrial fibrillation: a
      modeling study.
AB  - Maintenance of paroxysmal atrial fibrillation (AF) by fast rotors in the left
      atrium (LA) or at the pulmonary veins (PVs) is not fully understood. To gain
      insight into this dynamic and complex process, we studied the role of the
      heterogeneous distribution of transmembrane currents in the PVs and LA junction
      (PV-LAJ) in the localization of rotors in the PVs. We also investigated whether
      simple pacing protocols could be used to predict rotor drift in the PV-LAJ.
      Experimentally observed heterogeneities in IK1, IKs, IKr, Ito, and ICaL in the PV
      LAJ were incorporated into two- and pseudo three-dimensional models of
      Courtemanche-Ramirez-Nattel-Kneller human atrial kinetics to simulate various
      conditions and investigate rotor drifting mechanisms. Spatial gradients in the
      currents resulted in shorter action potential duration, minimum diastolic
      potential that was less negative, and slower upstroke and conduction velocity for
      rotors in the PV region than in the LA. Rotors under such conditions drifted
      toward the PV and stabilized at the shortest action potential duration and less
      excitable region, consistent with drift direction under intercellular coupling
      heterogeneities and regardless of the geometrical constraint in the PVs.
      Simulations with various IK1 gradient conditions and current-voltage
      relationships substantiated its major role in the rotor drift. In our 1:1 pacing
      protocol, we found that among various action potential properties, only the
      minimum diastolic potential gradient was a rate-independent predictor of rotor
      drift direction. Consistent with experimental and clinical AF studies,
      simulations in an electrophysiologically heterogeneous model of the PV-LAJ showed
      rotor attraction toward the PV. Our simulations suggest that IK1 heterogeneity is
      dominant compared to other currents in determining the drift direction through
      its impact on the excitability gradient. These results provide a believed novel
      framework for understanding the complex dynamics of rotors in AF. 

PMID- 24739181
TI  - Collagen I self-assembly: revealing the developing structures that generate
      turbidity.
AB  - Type I collagen gels are routinely used in biophysical studies and bioengineering
      applications. The structural and mechanical properties of these fibrillar
      matrices depend on the conditions under which collagen fibrillogenesis proceeds,
      and developing a fuller understanding of this process will enhance control over
      gel properties. Turbidity measurements have long been the method of choice for
      monitoring developing gels, whereas imaging methods are regularly used to
      visualize fully developed gels. In this study, turbidity and confocal reflectance
      microscopy (CRM) were simultaneously employed to track collagen fibrillogenesis
      and reconcile the information reported by the two techniques, with confocal
      fluorescence microscopy (CFM) used to supplement information about early events
      in fibrillogenesis. Time-lapse images of 0.5 mg/ml, 1.0 mg/ml, and 2.0 mg/ml acid
      solubilized collagen I gels forming at 27 degrees C, 32 degrees C, and 37 degrees
      C were collected. It was found that in situ turbidity measured in a scanning
      transmittance configuration was interchangeable with traditional turbidity
      measurements using a spectrophotometer. CRM and CFM were employed to reveal the
      structures responsible for the turbidity that develops during collagen self
      assembly. Information from CRM and transmittance images was collapsed into
      straightforward single variables; total intensity in CRM images tracked turbidity
      development closely for all collagen gels investigated, and the two techniques
      were similarly sensitive to fibril number and dimension. Complementary CRM, CFM,
      and in situ turbidity measurements revealed that fibril and network formation
      occurred before substantial turbidity was present, and the majority of increasing
      turbidity during collagen self-assembly was due to increasing fibril thickness.

PMID- 24739182
TI  - Rebuttal to a comment by Richard E. Waugh on our article "Yield strength of human
      erythrocyte membranes to impulsive stretching".

PMID- 24739183
TI  - Forty-percent area strain in red cell membranes?-Doubtful.

PMID- 24739185
TI  - Optimal flagging combinations for best performance of five blood cell analyzers.
AB  - INTRODUCTION: Corelab automation needs increasingly more efficient hematology
      analyzers and algorithms to adequately detect abnormal samples. The aim of this
      study is to assess the effect of combining flags or to adjust their trigger level
      to identify positive samples for further detection within a smear. METHODS: Five
      hundred and seventeen EDTA samples from patients followed for hematological
      malignancies were randomly analyzed on Sysmex XE2100 and XN2000, Abbott Cell-Dyn
      Sapphire, Beckman Coulter DXH800 and Siemens ADVIA 2120. A blood smear as well as
      a buffy coat was further performed for each of them. RESULTS: Our results shows
      that depending on the flags, the combinations of them and the thresholds we use,
      analyzers can provide extremely variable results in their performances for
      detecting abnormal cells. ADVIA and XN2000 show remarkable performance for blasts
      detection. DXH800 is the most sensitive for the detection of abnormal
      lymphocytes, while XN outperforms the market for immature granulocytes and
      nucleated red blood cell. CONCLUSION: Flagging performances have been shown to be
      inconsistent among the different manufacturers. This article should help
      laboratory professionals in their quest for the best flagging schemes and give
      them a baseline in the selection of the most appropriate analyzer.

PMID- 24739184
TI  - Indolicidin binding induces thinning of a lipid bilayer.
AB  - We use all-atom molecular dynamics simulations on a massive scale to compute the
      standard binding free energy of the 13-residue antimicrobial peptide indolicidin
      to a lipid bilayer. The analysis of statistical convergence reveals systematic
      sampling errors that correlate with reorganization of the bilayer on the
      microsecond timescale and persist throughout a total of 1.4 ms of sampling.
      Consistent with experimental observations, indolicidin induces membrane thinning,
      although the simulations significantly overestimate the lipophilicity of the
      peptide.

PMID- 24739186
TI  - National High School Athlete Concussion Rates From 2005-2006 to 2011-2012.
AB  - BACKGROUND: High school athletes are at risk for concussions. Although a
      previously published study showed an increase in concussion rates for a single
      school district, it remains unknown if the rate of concussions among high school
      athletes is increasing nationally. PURPOSE: To investigate national high school
      athlete concussion rates over time. STUDY DESIGN: Descriptive epidemiologic
      study. METHODS: The rate of concussions per 1000 athlete-exposures was calculated
      for academic years 2005-2006 through 2011-2012 using the High School Reporting
      Information Online sports injury surveillance system. RESULTS: During the 7-year
      period of this study, High School Reporting Information Online captured 4024
      concussions with overall concussion diagnosis rates increasing significantly from
      0.23 to 0.51 (P = .004). Concussion diagnosis rates increased for each of the 9
      sports studied, with 5 sports having statistically significant increases over
      this 7-year period. CONCLUSION: The study analysis indicates that national
      concussion diagnosis rates for high school sports have increased significantly
      over time.

PMID- 24739188
TI  - Molecular epidemiology of norovirus from patients with acute gastroenteritis in
      northwestern Spain.
AB  - The high incidence of norovirus (NoV) infections seems to be related to the
      emergence of new variants that evolved by genetic drift of the capsid gene. In
      this work, that represents a first effort to describe the molecular epidemiology
      of NoV in the northwest of Spain, a total of eight different NoV genotypes
      (GII.1, GII.3, GII.4, GII.6, GII.7, GII.12, GII.13, GII.14) were detected. The
      major genotypes observed were GII.4 (45.42%) and GII.14 (34.9%), being detected
      in all age groups. In addition, and although most of GII.4 sequences belonged to
      2006b (7.2%) and 2010 (50.35%) variants, the presence of new NoV variants was
      observed. Phylogenetic analysis revealed that a high number of GII.4 sequences
      (35.24%) could be assigned to the newly emerging Sydney 2012 variant, even during
      late 2010. The high prevalence of NoV GII.14 observed in this study may indicate
      the emergence of this genotype in Spain.

PMID- 24739187
TI  - The in vitro GcMAF effects on endocannabinoid system transcriptionomics, receptor
      formation, and cell activity of autism-derived macrophages.
AB  - BACKGROUND: Immune system dysregulation is well-recognized in autism and thought
      to be part of the etiology of this disorder. The endocannabinoid system is a key
      regulator of the immune system via the cannabinoid receptor type 2 (CB2R) which
      is highly expressed on macrophages and microglial cells. We have previously
      published significant differences in peripheral blood mononuclear cell CB2R gene
      expression in the autism population. The use of the Gc protein-derived Macrophage
      Activating Factor (GcMAF), an endogenous glycosylated vitamin D binding protein
      responsible for macrophage cell activation has demonstrated positive effects in
      the treatment of autistic children. In this current study, we investigated the in
      vitro effects of GcMAF treatment on the endocannabinoid system gene expression,
      as well as cellular activation in blood monocyte-derived macrophages (BMDMs) from
      autistic patients compared to age-matched healthy developing controls. METHODS:
      To achieve these goals, we used biomolecular, biochemical and immunocytochemical
      methods. RESULTS: GcMAF treatment was able to normalize the observed differences
      in dysregulated gene expression of the endocannabinoid system of the autism
      group. GcMAF also down-regulated the over-activation of BMDMs from autistic
      children. CONCLUSIONS: This study presents the first observations of GcMAF
      effects on the transcriptionomics of the endocannabinoid system and expression of
      CB2R protein. These data point to a potential nexus between endocannabinoids,
      vitamin D and its transporter proteins, and the immune dysregulations observed
      with autism.

PMID- 24739189
TI  - European Society for Pediatric Gastroenterology, Hepatology, and
      Nutrition/European Society for Pediatric Infectious Diseases evidence-based
      guidelines for the management of acute gastroenteritis in children in Europe:
      update 2014.
AB  - OBJECTIVES: These guidelines update and extend evidence-based indications for the
      management of children with acute gastroenteritis in Europe. METHODS: The
      guideline development group formulated questions, identified data, and formulated
      recommendations. The latter were graded with the Muir Gray system and, in
      parallel, with the Grading of Recommendations, Assessment, Development and
      Evaluations system. RESULTS: Gastroenteritis severity is linked to etiology, and
      rotavirus is the most severe infectious agent and is frequently associated with
      dehydration. Dehydration reflects severity and should be monitored by established
      score systems. Investigations are generally not needed. Oral rehydration with
      hypoosmolar solution is the major treatment and should start as soon as possible.
      Breast-feeding should not be interrupted. Regular feeding should continue with no
      dietary changes including milk. Data suggest that in the hospital setting, in non
      breast-fed infants and young children, lactose-free feeds can be considered in
      the management of gastroenteritis. Active therapy may reduce the duration and
      severity of diarrhea. Effective interventions include administration of specific
      probiotics such as Lactobacillus GG or Saccharomyces boulardii, diosmectite or
      racecadotril. Anti-infectious drugs should be given in exceptional cases.
      Ondansetron is effective against vomiting, but its routine use requires safety
      clearance given the warning about severe cardiac effects. Hospitalization should
      generally be reserved for children requiring enteral/parenteral rehydration; most
      cases may be managed in an outpatients setting. Enteral rehydration is superior
      to intravenous rehydration. Ultrarapid schemes of intravenous rehydration are not
      superior to standard schemes and may be associated with higher readmission rates.
      CONCLUSIONS: Acute gastroenteritis is best managed using a few simple, well
      defined medical interventions.

PMID- 24739190
TI  - Molecular cloning and characterization of genes involved in rosmarinic acid
      biosynthesis from Prunella vulgaris.
AB  - Prunella vulgaris L., commonly known as "self-heal" or "heal-all," is a perennial
      herb with a long history of medicinal use. Phenylalanine ammonia-lyase (PAL),
      cinnamate 4-hydroxylase (C4H), and 4-coumarate:coenzyme-A (CoA) ligase (4CL) are
      important enzymes in the phenylpropanoid pathway and in the accumulation of
      rosmarinic acid (RA), which is a major secondary metabolite in P. vulgaris. In
      this study, we isolated cDNAs encoding PvPAL, PvC4H, and Pv4CL from P. vulgaris
      using rapid amplification of cDNA ends polymerase chain reaction (PCR). The amino
      acid sequence alignments of PvPAL, PvC4H, and Pv4CL showed high sequence identity
      to those of other plants. Quantitative real-time PCR analysis was used to
      determine the transcript levels of genes involved in RA biosynthesis in the
      flowers, leaves, stems, and roots of P. vulgaris. The transcript levels of PvPAL,
      PvC4H, and Pv4CL1 were the highest in flowers, whereas Pv4CL2 was the highest in
      roots. High-performance liquid chromatography analysis also showed the highest RA
      content in the flowers (3.71 mg/g dry weight). We suggest that the expression of
      the PvPAL, PvC4H, and Pv4CL1 genes is correlated with the accumulation of RA. Our
      results revealed that P. vulgaris flowers are appropriate for medicinal usage,
      and our findings provide support for increasing RA production in this plant.

PMID- 24739191
TI  - Neutral biogeography and the evolution of climatic niches.
AB  - Recent debate on whether climatic niches are conserved through time has focused
      on how phylogenetic niche conservatism can be measured by deviations from a
      Brownian motion model of evolutionary change. However, there has been no
      evaluation of this methodological approach. In particular, the fact that climatic
      niches are usually obtained from distribution data and are thus heavily
      influenced by biogeographic factors has largely been overlooked. Our main
      objective here was to test whether patterns of climatic niche evolution that are
      frequently observed might arise from neutral dynamics rather than from adaptive
      scenarios. We developed a model inspired by neutral biodiversity theory, where
      individuals disperse, compete, and undergo speciation independently of climate.
      We then sampled the climatic niches of species according to their geographic
      position and showed that even when species evolve independently of climate, their
      niches can nonetheless exhibit evolutionary patterns strongly differing from
      Brownian motion. Indeed, climatic niche evolution is better captured by a model
      of punctuated evolution with constraints due to landscape boundaries, two
      features that are traditionally interpreted as evidence for selective processes
      acting on the niche. We therefore suggest that deviation from Brownian motion
      alone should not be used as evidence for phylogenetic niche conservatism but that
      information on phenotypic traits directly linked to physiology is required to
      demonstrate that climatic niches have been conserved through time.

PMID- 24739192
TI  - A novel multiscale assessment of community assembly across time, space, and
      functional niche.
AB  - A basic ecological tenet is that organisms in a community occupy different niches
      and have different traits, but how consistently competition, selection, and
      phylogenetic effects structure communities remains uncertain. Are all communities
      created equal? We examine how mammalian carnivoran communities are assembled with
      regard to mass, diet, and locomotion. Here, we use a multivariate nearest
      neighbor framework to examine multiple North American localities spanning 3
      million years to determine whether community assembly is consistent through time
      and four modern localities around the world to assess the effects of habitat.
      Additionally, we examined how trait patterns differ among families and how family
      level evolutionary effects affect them. We found some broadly consistent
      patterns, although differences are more pronounced than similarities. Diet is
      more affected by evolutionary constraints than by time or place. Locomotion is
      most affected by habitat, and the ability to partition niches is related to
      habitat heterogeneity. Mass is influenced by family, but also by habitat and the
      mass-selective extinction events at the end-Pleistocene. These findings indicate
      that assembly patterns are not largely determined by within-community
      interactions but instead show that each community is a product of its independent
      variables.

PMID- 24739193
TI  - Species abundance, not diet breadth, drives the persistence of the most linked
      pollinators as plant-pollinator networks disassemble.
AB  - Theoretical and simulation studies predict that the order of species loss from
      mutualist networks with respect to how linked species are to other species within
      the network will determine the rate at which networks collapse. However, the
      empirical order of species loss with respect to linkage has rarely been
      investigated. Furthermore, a species' linkage is a composite of its diet breadth
      and its abundance, yet the relative importance of these two factors in
      determining species loss order is poorly known. Here we explore the order of
      pollinator species loss in two contrasting study systems undergoing land-use
      intensification, using >20,000 pollinator specimens. We found that a pollinator
      species' linkage, as measured independently within plant-pollinator networks,
      positively predicted its persistence at human-disturbed sites in three of four
      analyses. The strongest predictor of persistence in all analyses was pollinator
      species abundance. In contrast, diet breadth poorly predicted persistence.
      Overall, our results suggest that community disassembly order buffers plant
      pollinator networks against environmental change by retaining the highly linked
      species that make a disproportionate contribution to network robustness.
      Furthermore, these highly linked species likely persist because they are also the
      most common species, not because they are dietary generalists.

PMID- 24739194
TI  - Coexistence of specialist and generalist species is shaped by dispersal and
      environmental factors.
AB  - Disentangling the mechanisms mediating the coexistence of habitat specialists and
      generalists has been a long-standing subject of investigation. However, the roles
      of species traits and environmental and spatial factors have not been assessed in
      a unifying theoretical framework. Theory suggests that specialist species are
      more competitive in natural communities. However, empirical work has shown that
      specialist species are declining worldwide due to habitat loss and fragmentation.
      We addressed the question of the coexistence of specialist and generalist species
      with a spatially explicit metacommunity model in continuous and heterogeneous
      environments. We characterized how species' dispersal abilities, the number of
      interacting species, environmental spatial autocorrelation, and disturbance
      impact community composition. Our results demonstrated that species' dispersal
      ability and the number of interacting species had a drastic influence on the
      composition of metacommunities. More specialized species coexisted when species
      had large dispersal abilities and when the number of interacting species was
      high. Disturbance selected against highly specialized species, whereas
      environmental spatial autocorrelation had a marginal impact. Interestingly,
      species richness and niche breadth were mainly positively correlated at the
      community scale but were negatively correlated at the metacommunity scale.
      Numerous diversely specialized species can thus coexist, but both species'
      intrinsic traits and environmental factors interact to shape the specialization
      signatures of communities at both the local and global scales.

PMID- 24739195
TI  - Roles of alternative prey for mesopredators on trophic cascades in intraguild
      predation systems: a theoretical perspective.
AB  - Declines of apex predators can cause dramatic increases of smaller predators and
      ensuing collapses of their prey. However, recent empirical evidence finds that
      the disappearance of apex predators does not reduce but can increase prey
      populations. This poses a great challenge in managing species interactions
      involving mesopredator release. Here we analyze a mathematical model to explain
      variable consequences of apex predator loss and to develop management guidelines
      for prey conservation. The model formulates an intraguild predation system (apex
      predators, mesopredators, and their shared prey) with mesopredators supplied with
      additional alternative prey. We show that apex predator loss causes only negative
      effects on shared prey without alternative prey but has either negative or
      positive effects with alternative prey. Moreover, when alternative prey is highly
      abundant, apex predator loss causes strong mesopredator release and reduces
      shared prey greatly. Finally, the model suggests that a viable management
      strategy to restore shared prey under much uncertainty about a target system is
      to allocate a limited control effort not only to both predators but also to
      alternative prey. Alternative prey for mesopredators may be a crucial ingredient
      that controls the cascading dynamics of intraguild predation systems and should
      be considered as an important management target.

PMID- 24739196
TI  - Reproductive foragers: male spiders choose mates by selecting among competitive
      environments.
AB  - Mate choice frequently operates differently for males and females as a
      consequence of male competition for mates. Competitive interactions can alter the
      fitness payoffs of choice and the realization of preferences under natural
      conditions, yet the majority of male choice studies still use binary trials that
      ignore social factors. Here we test the importance of contest dynamics in male
      choice using a framework in which females are considered analogous to foraging
      patches that are subject to competition. We track the mate choices and
      interactions of 640 spiders (Nephila plumipes) before and after manipulation of
      competition within enclosures, modeling the expected fitness payoffs of each
      male's actual choices and comparing these with all alternative choices. Many
      males choose new mates once social conditions change and achieve higher fitness
      than predicted under random movement. Males do not simply move to larger females
      but choose favorable competitive environments that balance competition and female
      fecundity, thereby increasing their fitness payoffs. Further, we show for the
      first time that prior-residence effects, which are known to influence male
      contests, also have a strong influence in male reproductive contests and can
      shape male mate choice. These results highlight the importance of situating male
      choice studies in the relevant social context, as intrasexual interactions can
      have profound effects on the realization and payoffs of male mate-choice
      strategies.

PMID- 24739197
TI  - Digestive capacity and toxicity cause mixed diets in red knots that maximize
      energy intake rate.
AB  - Among energy-maximizing animals, preferences for different prey can be explained
      by ranking the prey according to their energetic content. However, diet choice
      also depends on characteristics of the predator, such as the need to ingest
      necessary nutrients and the constraints imposed by digestion and toxins in food.
      In combination, these factors can lead to mixed diets in which the energetically
      most profitable food is not eaten exclusively even when it is abundant. We
      studied diet choice in red knots (Calidris canutus canutus) feeding on mollusks
      at a West African wintering site. At this site, the birds fed primarily on two
      species of bivalves, a thick-shelled one (Dosinia isocardia) that imposed a
      digestive constraint and a thin-shelled one (Loripes lucinalis) that imposed a
      toxin constraint. The latter species is toxic due to its symbiotic association
      with sulfide-oxidizing bacteria. We estimated experimentally the parameters of a
      linear programming model that includes both digestive and toxin constraints,
      leading to the prediction that red knots should eat a mixture of both mollusk
      species to maximize energy intake. The model correctly predicted the preferences
      of the captive birds, which depended on the digestive quality and toxicity of
      their previous diet. At our study site, energy-maximizing red knots appear to
      select a mixed diet as a result of the simultaneous effects of digestive and
      toxin constraints.

PMID- 24739198
TI  - Developmental timing of signals affects information content: song complexity but
      not consistency reflects innate immune strategy in male song sparrows.
AB  - In short-lived animals, innate immunity is an important component of fitness and
      quality. Although receivers cannot generally assess a signaler's immune function
      directly, sexually selected displays such as birdsong may reflect past or current
      condition. We investigated the degree to which song complexity and consistency,
      thought to reflect condition over different developmental timescales, predict
      multiple aspects of innate immunity in male song sparrows (Melospiza melodia). We
      also investigated correlations among immune measures. Noncellular components of
      innate immunity (soluble blood proteins including natural antibody and other
      protective proteins) were negatively related to cellular (phagocytosis-based)
      components, suggesting trade-offs within innate immune protection. This pattern
      underscores the risk of inferring "immunocompetence" from a single metric. Song
      complexity, a permanent trait in this species, was positively related to
      noncellular relative to cellular immune components and may thus provide
      information as to the singer's innate immune strategy (investment in noncellular
      vs. cellular activity). Such a relationship could arise through shared timing of
      song learning and antibody repertoire development in early life. Singing
      consistency, thought to track variation in current condition and measured at both
      whole-song and syllable scales, did not predict any immune measures.
      Developmental timing of signals thus appears to influence their information
      content.

PMID- 24739199
TI  - Synergism of natural selection and introgression in the origin of a new species.
AB  - This article explores how introgressive hybridization enhances the evolutionary
      effects of natural selection and how, reciprocally, natural selection can enhance
      the evolutionary effects of introgression. Both types of interaction were
      observed during a 40-year study of Darwin's finches (Geospiza) on the small
      Galapagos island of Daphne Major. Hybrids, produced rarely by Geospiza fortis
      (medium ground finch) breeding with Geospiza scandens (cactus finch) and Geospiza
      fuliginosa (small ground finch), survived and bred as well as the parental
      species in the past 3 decades. By backcrossing, they increased the standing
      genetic variation and thereby the evolutionary responsiveness of the populations
      to natural selection. Natural selection occurred in droughts and oscillated in
      direction as a result of climatically induced fluctuations in food composition.
      Introgressive hybridization has led to the formation of a new lineage. It was
      initiated by a large, introgressed, hybrid male with a unique song and genetic
      marker that immigrated from the nearby island of Santa Cruz and bred with local
      hybrids and with G. fortis. All members of the lineage died in the 2003-2005
      drought except a brother and a sister, who then bred with each other. Subsequent
      increase in the lineage was facilitated by selective mortality of the largest G.
      fortis. Breeding endogamously, the lineage is behaving as a biological species.

PMID- 24739200
TI  - Adaptations between ecotypes and along environmental gradients in Panicum
      virgatum.
AB  - Determining the patterns and mechanisms of natural selection in the wild is of
      fundamental importance to understanding the differentiation of populations and
      the evolution of new species. However, it is often unknown the extent to which
      adaptive genetic variation is distributed among ecotypes between distinct
      habitats versus along large-scale geographic environmental gradients, such as
      those that track latitude. Classic studies of selection in the wild in
      switchgrass, Panicum virgatum, tested for adaptation at both of these levels of
      natural variation. Here we review what these field experiments and modern
      agronomic field trials have taught us about natural variation and selection at
      both the ecotype and environmental gradient levels in P. virgatum. With recent
      genome sequencing efforts in P. virgatum, it is poised to become an excellent
      system for understanding the adaptation of grassland species across the eastern
      half of North America. The identification of genetic loci involved in different
      types of adaptations will help to understand the evolutionary mechanisms of
      diversification within P. virgatum and provide useful information for the
      breeding of high-yielding cultivars for different ecoregions.

PMID- 24739201
TI  - The cost of reinforcement: selection on flower color in allopatric populations of
      Phlox drummondii.
AB  - Reinforcement is the process by which increased reproductive isolation between
      incipient species evolves due to selection against maladaptive hybrids or costly
      hybrid mating. Reinforcement is predicted to create a pattern of greater
      prezygotic reproductive isolation in regions where the two species co-occur,
      sympatry, than in allopatry. Although most research on reinforcement focuses on
      understanding the evolutionary forces acting in sympatry, here we consider what
      prevents the alleles conferring greater reproductive isolation from spreading
      into allopatry. We investigate flower color divergence in the wildflower Phlox
      drummondii, which is caused by reinforcement in the regions sympatric with its
      congener Phlox cuspidata. Specifically, we performed common garden field
      experiments and pollinator observations to estimate selection acting on flower
      color variation in allopatry. We combine our estimates of maternal and paternal
      fitness using simulations and predict how flower color alleles migrating from
      sympatry will evolve in allopatry. Our results suggest that strong pollinator
      preference for the ancestral flower color in allopatry can maintain divergence
      between allopatric and sympatric populations.

PMID- 24739202
TI  - Genome-wide association mapping of phenotypic traits subject to a range of
      intensities of natural selection in Timema cristinae.
AB  - The genetic architecture of adaptive traits can reflect the evolutionary history
      of populations and also shape divergence among populations. Despite this central
      role in evolution, relatively little is known regarding the genetic architecture
      of adaptive traits in nature, particularly for traits subject to known selection
      intensities. Here we quantitatively describe the genetic architecture of traits
      that are subject to known intensities of differential selection between host
      plant species in Timema cristinae stick insects. Specifically, we used phenotypic
      measurements of 10 traits and 211,004 single-nucleotide polymorphisms (SNPs) to
      conduct multilocus genome-wide association mapping. We identified a modest number
      of SNPs that were associated with traits and sometimes explained a large
      proportion of trait variation. These SNPs varied in their strength of association
      with traits, and both major and minor effect loci were discovered. However, we
      found no relationship between variation in levels of divergence among traits in
      nature and variation in parameters describing the genetic architecture of those
      same traits. Our results provide a first step toward identifying loci underlying
      adaptation in T. cristinae. Future studies will examine the genomic location,
      population differentiation, and response to selection of the trait-associated
      SNPs described here.

PMID- 24739203
TI  - Frequency-dependent selection can lead to evolution of high mutation rates.
AB  - Theoretical and experimental studies have shown that high mutation rates can be
      advantageous, especially in novel or fluctuating environments. Here we examine
      how frequency-dependent competition may lead to fluctuations in trait frequencies
      that exert upward selective pressure on mutation rates. We use a mathematical
      model to show that cyclical trait dynamics generated by "rock-paper-scissors"
      competition can cause the mutation rate in a population to converge to a high
      evolutionarily stable mutation rate, reflecting a trade-off between generating
      novelty and reproducing past success. Introducing recombination lowers the
      evolutionarily stable mutation rate but allows stable coexistence between
      mutation rates above and below the evolutionarily stable rate. Even considering
      strong mutational load and ignoring the costs of faithful replication, evolution
      favors positive mutation rates if the selective advantage of prevailing in
      competition exceeds the ratio of recombining to nonrecombining offspring. We
      discuss a number of genomic mechanisms that may meet our theoretical requirements
      for the adaptive evolution of mutation. Overall, our results suggest that local
      mutation rates may be higher on genes influencing cyclical competition and that
      global mutation rates in asexual species may be higher in populations subject to
      strong cyclical competition.

PMID- 24739204
TI  - From fine-scale foraging to home ranges: a semivariance approach to identifying
      movement modes across spatiotemporal scales.
AB  - Understanding animal movement is a key challenge in ecology and conservation
      biology. Relocation data often represent a complex mixture of different movement
      behaviors, and reliably decomposing this mix into its component parts is an
      unresolved problem in movement ecology. Traditional approaches, such as composite
      random walk models, require that the timescales characterizing the movement are
      all similar to the usually arbitrary data-sampling rate. Movement behaviors such
      as long-distance searching and fine-scale foraging, however, are often intermixed
      but operate on vastly different spatial and temporal scales. An approach that
      integrates the full sweep of movement behaviors across scales is currently
      lacking. Here we show how the semivariance function (SVF) of a stochastic
      movement process can both identify multiple movement modes and solve the sampling
      rate problem. We express a broad range of continuous-space, continuous-time
      stochastic movement models in terms of their SVFs, connect them to relocation
      data via variogram regression, and compare them using standard model selection
      techniques. We illustrate our approach using Mongolian gazelle relocation data
      and show that gazelle movement is characterized by ballistic foraging movements
      on a 6-h timescale, fast diffusive searching with a 10-week timescale, and
      asymptotic diffusion over longer timescales.

PMID- 24739205
TI  - A cross-sectional survey assessing the acceptability and feasibility of self
      report electronic data collection about health risks from patients attending an
      Aboriginal Community Controlled Health Service.
AB  - BACKGROUND: Aboriginal Australians experience significantly worse health and a
      higher burden of chronic disease than non-Aboriginal Australians. Electronic self
      report data collection is a systematic means of collecting data about health risk
      factors which could help to overcome screening barriers and assist in the
      provision of preventive health care. Yet this approach has not been tested in an
      Aboriginal health care setting. Therefore, the aim of this study was to examine
      the acceptability and feasibility of a health risk questionnaire administered on
      a touch screen laptop computer for patients attending an Aboriginal Community
      Controlled Health Service (ACCHS). METHODS: In 2012, consecutive adult patients
      attending an ACCHS in rural New South Wales, Australia, were asked to complete a
      health risk survey on a touch screen computer. Health risk factors assessed in
      the questionnaire included smoking status, body mass index, and level of physical
      activity. The questionnaire included visual cues to improve accuracy and minimise
      literacy barriers and was completed while participants were waiting for their
      appointment. RESULTS: A total of 188 participants completed the questionnaire,
      with a consent rate of 71%. The mean time taken to complete the questionnaire was
      less than 12 minutes. Over 90% of participants agreed that: the questionnaire
      instructions were easy to follow; the touch screen computer was easy to use; they
      had enough privacy; the questions were easy to understand; they felt comfortable
      answering all the questions. CONCLUSIONS: Results indicate that the use of a
      touch screen questionnaire to collect information from patients about health risk
      factors affecting Aboriginal Australians is feasible and acceptable in the ACCHS
      setting. This approach has potential to improve identification and management of
      at-risk individuals, therein providing significant opportunities to reduce the
      burden of disease among Aboriginal Australians.

PMID- 24739206
TI  - Revisiting AFLP fingerprinting for an unbiased assessment of genetic structure
      and differentiation of taurine and zebu cattle.
AB  - BACKGROUND: Descendants from the extinct aurochs (Bos primigenius), taurine (Bos
      taurus) and zebu cattle (Bos indicus) were domesticated 10,000 years ago in
      Southwestern and Southern Asia, respectively, and colonized the world undergoing
      complex events of admixture and selection. Molecular data, in particular genome
      wide single nucleotide polymorphism (SNP) markers, can complement historic and
      archaeological records to elucidate these past events. However, SNP ascertainment
      in cattle has been optimized for taurine breeds, imposing limitations to the
      study of diversity in zebu cattle. As amplified fragment length polymorphism
      (AFLP) markers are discovered and genotyped as the samples are assayed, this type
      of marker is free of ascertainment bias. In order to obtain unbiased assessments
      of genetic differentiation and structure in taurine and zebu cattle, we analyzed
      a dataset of 135 AFLP markers in 1,593 samples from 13 zebu and 58 taurine
      breeds, representing nine continental areas. RESULTS: We found a geographical
      pattern of expected heterozygosity in European taurine breeds decreasing with the
      distance from the domestication centre, arguing against a large-scale
      introgression from European or African aurochs. Zebu cattle were found to be at
      least as diverse as taurine cattle. Western African zebu cattle were found to
      have diverged more from Indian zebu than South American zebu. Model-based
      clustering and ancestry informative markers analyses suggested that this is due
      to taurine introgression. Although a large part of South American zebu cattle
      also descend from taurine cows, we did not detect significant levels of taurine
      ancestry in these breeds, probably because of systematic backcrossing with zebu
      bulls. Furthermore, limited zebu introgression was found in Podolian taurine
      breeds in Italy. CONCLUSIONS: The assessment of cattle diversity reported here
      contributes an unbiased global view to genetic differentiation and structure of
      taurine and zebu cattle populations, which is essential for an effective
      conservation of the bovine genetic resources.

PMID- 24739207
TI  - Transversus abdominis plane block for analgesia after Cesarean delivery. A
      systematic review.
AB  - Cesarean delivery is a major surgical procedure, after which a woman can
      experience substantial postoperative discomfort or pain. Inadequate postoperative
      analgesia is one of the most common reasons for poor patient satisfaction
      following cesarean delivery. Although spinal or systemic opioids are currently
      the gold standard to achieve effective analgesia, they are often associated with
      side effects. In the last few years there has been growing interest in abdominal
      plane blocks, with promising data on their efficacy. The transversus abdominis
      plane (TAP) block is a regional analgesic technique which is gaining acceptance
      in postoperative analgesia for lower abdominal surgeries. In this systematic
      review of articles published as of 31 December 2013, we searched the principal
      medical databases for randomized controlled trials that assessed the efficacy of
      ultrasound (US)-guided TAP block following cesarean delivery and reported on
      postoperative opioid consumption and pain score, opioid-related side-effects and
      patient satisfaction. Although controversy surrounds the utility of US-guided TAP
      block in cesarean section, evidence suggests that when correctly executed as part
      of a multimodal analgesic regimen, TAP block may reduce postoperative opioid
      consumption and opioid-related side effects, improving postoperative pain control
      and patient satisfaction. Further studies are necessary to explore this field of
      research. 

PMID- 24739208
TI  - Incidence of Kaposi's sarcoma and associated mortality in Fresno, California,
      1998 to 2012.
AB  - OBJECTIVE: The incidence of Kaposi's sarcoma (KS) decreased dramatically after
      the introduction of highly active antiretroviral therapy (HAART). This study
      determined the ongoing incidence of and mortality from KS in HIV-infected adults
      from 1998-2012 in Fresno County, California. The role of virologic control and
      immune reconstitution was assessed. METHODS: Incident cases were identified from
      the state Electronic HIV/AIDS Reporting System (EHARS), the California Cancer
      Registry, and hospital records of the county HIV treatment center. RESULTS: From
      1998-2012, the average incidence of KS was 0.51 cases per 100,000 person-years.
      Of the 66 cases of KS there were 20 deaths, with 85% of the mortality occurring
      in the first 12 months. Among patients on HAART achieving HIV RNA <400 copies/uL,
      but with a <50 cell/uL increase in CD4 count there was no improvement in
      mortality. CONCLUSIONS: The incidence of KS remains stable since 1998 with a 12
      month mortality of 30%.

PMID- 24739209
TI  - African-American patients' preferences for a health center campaign promoting HIV
      testing: an exploratory study and future directions.
AB  - OBJECTIVE: In 2006, the US Centers for Disease Control and Prevention recommended
      routine HIV testing in health care settings and called for HIV testing campaigns
      targeting African Americans. In a 2011 national survey, 63% of African Americans
      wanted information on HIV testing. METHODS: In our study, 176 African Americans
      were surveyed to determine channels and spokespersons for an HIV testing
      campaign. RESULTS: Among 9 media channels, the top 3 ranked as "very likely" to
      convince them to get HIV tested were television, poster, and brochure. Among 10
      spokespersons, the top 3 were doctor, nurse, and "real person like me."
      CONCLUSION: The media are a cost-effective strategy to promote HIV prevention.
      Posters and brochures are inexpensive and easy to reproduce for clinical
      settings. Television campaigns may be feasible in clinics with closed-circuit
      televisions. Research is needed on campaign messages. An effective health center
      HIV testing campaign may help mitigate the disproportionate toll HIV is having on
      African Americans.

PMID- 24739210
TI  - Case-finding of chronic obstructive pulmonary disease with questionnaire, peak
      flow measurements and spirometry: a cross-sectional study.
AB  - BACKGROUND: Spirometry is commonly accepted as the gold standard for the
      diagnosis of COPD, but the reality remains that quality assured spirometry is not
      or cannot be provided universally around the globe. Adding PEF measurement to a
      screening questionnaire may rule out airflow limitation compatible with COPD
      rationalizing spirometry testing. METHODS: We conducted a cross-sectional survey
      in a sample of individuals 40-80 yrs. old in Dubai, UAE. They were invited to
      answer a short socio-demographic questionnaire including a report on current,
      past history of smoking, and had PEF measured, then they conducted spirometry to
      identify airflow limitation compatible with COPD. RESULTS: Overall, 525 (91.0%)
      participants performed PEF and spirometry (68% male, with a mean age of 59 years,
      17% UAE Nationals), 24% reported smoking of different sorts. Overall, 68
      participants (12.9%, 95% C.I. 10.3% to 16.1%) had airflow limitation compatible
      with COPD. PEFR alone identified 141 participants with airflow limitation
      compatible with COPD, with specificity of 80% and sensitivity of 73.5%.
      CONCLUSIONS: PEFR could be an easy, cheap, and non-biased tool to assist with the
      case-finding of COPD before confirmation with spirometry.

PMID- 24739211
TI  - Unexpected interplay of bonding height and energy level alignment at
      heteromolecular hybrid interfaces.
AB  - Although geometric and electronic properties of any physical or chemical system
      are always mutually coupled by the rules of quantum mechanics, counterintuitive
      coincidences between the two are sometimes observed. The coadsorption of the
      organic molecules 3,4,9,10-perylene tetracarboxylic dianhydride and copper-II
      phthalocyanine on Ag(111) represents such a case, since geometric and electronic
      structures appear to be decoupled: one molecule moves away from the substrate
      while its electronic structure indicates a stronger chemical interaction, and
      vice versa for the other. Our comprehensive experimental and ab-initio
      theoretical study reveals that, mediated by the metal surface, both species
      mutually amplify their charge-donating and -accepting characters, respectively.
      This resolves the apparent paradox, and demonstrates with exceptional clarity how
      geometric and electronic bonding parameters are intertwined at metal-organic
      interfaces. 

PMID- 24739212
TI  - Large cell anaplastic medulloblastoma metastatic to the scalp: tumor and derived
      stem-like cells features.
AB  - BACKGROUND: Extraneural metastases (ENM) rarely occur in medulloblastoma (MBL)
      patients and only few cases of subcutaneous localizations have been described.
      ENM indicate an aggressive disease associated with a worse prognosis. The
      characterization of metastatic tumours might be useful to understand their
      pathogenesis and to identify the most appropriate therapeutic strategies. CASE
      PRESENTATION: We present the case of a child with Large Cell Anaplastic (LC/A)
      MBL, who developed multiple subcutaneous metastases in the scalp area after a
      ventriculo-peritoneal shunting procedure. The disease rapidly progressed and the
      child died despite chemotherapy and primary tumour surgical debulking.We
      molecularly classified the tumour as a group 3 MBL; in addition, we derived stem
      like cells (SLC) from a metastatic lesion. Primary tumour, metastases and SLC
      were further analysed, particularly focusing on features linked to the cutaneous
      dissemination. Indeed, molecules involved in angiogenesis, cell invasion and
      epidermal growth factor signalling resulted highly expressed. CONCLUSIONS: The
      present report describes a very rare case of subcutaneous metastatic MBL. The
      tumour, metastases and SLC have been clinically, pathologically and molecularly
      characterized. Our case is an example of multidisciplinary approach aiming to
      characterize MBL aggressive behaviour.

PMID- 24739213
TI  - Detection of subtle neurological alterations by the Catwalk XT gait analysis
      system.
AB  - BACKGROUND: A new version of the CatWalk XT system was evaluated as a tool for
      detecting very subtle alteration in gait based on higher speed sample rate; the
      system could also demonstrate minor changes in neurological function. In this
      study, we evaluated the neurological outcome of sciatic nerve injury intervened
      by local injection of hyaluronic acid. Using the CatWalk XT system, we looked for
      differences between treated and untreated groups and differences within the same
      group as a function of time so as to assess the power of the Catwalk XT system
      for detecting subtle neurological change. METHODS: Peripheral nerve injury was
      induced in 36 Sprague-Dawley rats by crushing the left sciatic nerve using a
      vessel clamp. The animals were randomized into one of two groups: Group I: crush
      injury as the control; Group II: crush injury and local application with
      hyaluronic acid. These animals were subjected to neurobehavior assessment,
      histomorphology evaluation, and electrophysiology study periodically. These data
      were retrieved for statistical analysis. RESULTS: The density of neurofilament
      and S-100 over the distal end of crushed nerve showed significant differences
      either in inter-group comparison at various time points or intra-group comparison
      from 7 to 28 days. Neuronal structure architecture, axon counts, intensity of
      myelination, electrophysiology, and collagen deposition demonstrate significant
      differences between the two groups. There was significant difference of SFI and
      angle of ankle in inter- group analysis from 7 to 28 days, but there were no
      significant differences in SFI and angle of ankle at time points of 7 and 14
      days. In the Cat Walk XT analysis, the intensity, print area, stance duration,
      and swing duration all showed detectable differences at 7, 14, 21, and 28 days,
      whereas there were no significant difference at 7 and 14 days with CatWalk 7
      testing. In addition, there were no significant differences of step sequence or
      regularity index between the two versions. CONCLUSION: Hyaluronic acid augmented
      nerve regeneration as early as 7 days after crush injury. This subtle
      neurological alteration could be detected through the CatWalk XT gait analysis
      but not the SFI, angle of ankle, or CatWalk 7 methods.

PMID- 24739214
TI  - Screening and confirmation of hereditary spherocytosis in children using a CELL
      DYN Sapphire haematology analyser.
AB  - INTRODUCTION: Multidimensional optical scatter of sphered erythrocytes can
      identify and enumerate hyperchromic erythrocytes, which might be used for
      hereditary spherocytosis (HS) screening. The flow cytometric eosin-5'-maleimide
      test (EMA) is highly sensitive and specific for HS as a confirmatory method. The
      aims of this study were to assess the utility of hyperchromic erythrocytes in HS
      screening and to evaluate the EMA test performed on CELL-DYN Sapphire analyser
      compared with the reference method. METHODS: Blood from 740 paediatric patients
      presenting at our institution was analysed in reticulocyte mode of the CELL-DYN
      Sapphire haematology analyser (Abbott Diagnostics) to obtain hyperchromic
      erythrocyte counts. The EMA test was performed using a flow cytometer as a
      reference, as well as CELL-DYN Sapphire as an investigational method. RESULTS:
      Hyperchromic erythrocytes were the highest in patients with HS (median 11.5%;
      range 5.1-29.2%). Patients with autoimmune haemolytic disease had significantly
      less hyperchromic erythrocytes (median 4.9%; range 0.0-18.3%). Hyperchromic
      erythrocytes showed a high area under the ROC curve: 0.972. At 4.9% cut-off,
      hyperchromic erythrocytes detected HS with 96.4% sensitivity and 99.1%
      specificity. The EMA test on CELL-DYN Sapphire correlated strongly with the
      reference test and had identical diagnostic power. Stability studies with blood
      from HS patients showed a significant decrease in hyperchromic erythrocytes after
      6 h storage. CONCLUSIONS: Measurement of hyperchromic erythrocytes is highly
      sensitive and specific for detecting HS and can be used for rapid and inexpensive
      screening. If required, the EMA test can be performed on CELL-DYN Sapphire or a
      standard flow cytometer for confirmation of HS.

PMID- 24739215
TI  - Identification of a novel ATP-binding cassette transporter involved in long-chain
      fatty acid import and its role in triacylglycerol accumulation in Rhodococcus
      jostii RHA1.
AB  - Members of the genus Rhodococcus are specialists in the biosynthesis and
      accumulation of triacylglycerols (TAGs). As no transport protein related to TAG
      metabolism has yet been characterized in these bacteria, we used the available
      genomic information of Rhodococcus jostii RHA1 to perform a broad survey of genes
      coding for putative lipid transporter proteins in this oleaginous micro-organism.
      Among the seven genes encoding putative lipid transporters, ro05645 (now called
      ltp1: lipid transporter protein) coding for an ATP-binding cassette protein was
      found clustered with others genes encoding enzymes catalysing the three putative
      acylation reactions of the Kennedy pathway for TAG synthesis. Overexpression of
      ltp1 in the RHA1 strain led to an increase of approximately sixfold and threefold
      in biomass and TAG production, respectively, when cells were cultivated on
      palmitic acid and oleic acid. Moreover, overexpression of ltp1 also promoted a
      significant increase in the uptake of a fluorescently labelled long-chain fatty
      acid (LCFA), as compared with the WT strain RHA1, and its further incorporation
      into the TAG fraction. Gluconate-grown cells showed increasing amounts of
      intracellular free fatty acids, but not of TAG, after overexpressing ltp1. Thus,
      for the first time to our knowledge, a transporter functionally related to TAG
      metabolism was identified in oleaginous rhodococci. Our results suggested that
      Ltp1 is an importer of LCFAs that plays a functional role in lipid homeostasis of
      R. jostii RHA1. 

PMID- 24739216
TI  - Protein turnover forms one of the highest maintenance costs in Lactococcus
      lactis.
AB  - Protein turnover plays an important role in cell metabolism by regulating
      metabolic fluxes. Furthermore, the energy costs for protein turnover have been
      estimated to account for up to a third of the total energy production during cell
      replication and hence may represent a major limiting factor in achieving either
      higher biomass or production yields. This work aimed to measure the specific
      growth rate (MU)-dependent abundance and turnover rate of individual proteins,
      estimate the ATP cost for protein production and turnover, and compare this with
      the total energy balance and other maintenance costs. The lactic acid bacteria
      model organism Lactococcus lactis was used to measure protein turnover rates at
      MU = 0.1 and 0.5 h(-1) in chemostat experiments. Individual turnover rates were
      measured for ~75% of the total proteome. On average, protein turnover increased
      by sevenfold with a fivefold increase in growth rate, whilst biomass yield
      increased by 35%. The median turnover rates found were higher than the specific
      growth rate of the bacterium, which suggests relatively high energy consumption
      for protein turnover. We found that protein turnover costs alone account for 38
      and 47% of the total energy produced at MU = 0.1 and 0.5 h(-1), respectively, and
      gene ontology groups Energy metabolism and Translation dominated synthesis costs
      at both growth rates studied. These results reflect the complexity of metabolic
      changes that occur in response to changes in environmental conditions, and
      signify the trade-off between biomass yield and the need to produce ATP for
      maintenance processes.

PMID- 24739217
TI  - Unravelling the complete genome sequence of Advenella mimigardefordensis strain
      DPN7T and novel insights in the catabolism of the xenobiotic polythioester
      precursor 3,3'-dithiodipropionate.
AB  - Advenella mimigardefordensis strain DPN7(T) is a remarkable betaproteobacterium
      because of its extraordinary ability to use the synthetic disulfide 3,3'
      dithiodipropionic acid (DTDP) as the sole carbon source and electron donor for
      aerobic growth. One application of DTDP is as a precursor substrate for
      biotechnically synthesized polythioesters (PTEs), which are interesting non
      degradable biopolymers applicable for plastics materials. Metabolic engineering
      for optimization of PTE production requires an understanding of DTDP conversion.
      The genome of A. mimigardefordensis strain DPN7(T) was sequenced and annotated.
      The circular chromosome was found to be composed of 4,740,516 bp and 4112
      predicted ORFs, whereas the circular plasmid consisted of 23,610 bp and 24
      predicted ORFs. The genes participating in DTDP catabolism had been characterized
      in detail previously, but knowing the complete genome sequence and with support
      of Tn5: :mob-induced mutants, putatively involved transporter proteins and a
      transcriptional regulator were also identified. Most probably, DTDP is
      transported into the cell by a specific tripartite tricarboxylate transport
      system and is then cleaved by the disulfide reductase LpdA, sulfoxygenated by the
      3-mercaptopropionate dioxygenase Mdo, activated by the CoA ligase SucCD and
      desulfinated by the acyl-CoA dehydrogenase-like desulfinase AcdA. Regulation of
      this pathway is presumably performed by a transcriptional regulator of the
      xenobiotic response element family. The excessive sulfate that is inevitably
      produced is secreted by the cells by a unique sulfate exporter of the CPA (cation
      : proton antiporter) superfamily.

PMID- 24739218
TI  - Trajectories of positive aging: observations from the women's health initiative
      study.
AB  - BACKGROUND: The purpose of this study was to describe the longitudinal
      trajectories and bidirectional relationships of the physical-social and emotional
      functioning (EF) dimensions of positive aging and to identify their baseline
      characteristics. METHODS: Women age 65 and older who enrolled in one or more
      Women's Health Initiative clinical trials (WHI CTs) and who had positive aging
      indicators measured at baseline and years 1, 3, 6, and 9 were included in these
      analyses (N = 2281). Analytic strategies included latent class growth modeling to
      identify longitudinal trajectories and multinomial logistic regression to examine
      the effects of baseline predictors on these trajectories. RESULTS: A five
      trajectory model was chosen to best represent the data. For Physical-Social
      Functioning (PSF), trajectory groups included Low Maintainer (8.3%), Mid-Low
      Improver (10.4%), Medium Decliner (10.7%), Mid-High Maintainer (31.2%), and High
      Maintainer (39.4%); for EF, trajectories included Low Maintainer (3%), Mid-Low
      Improver (9%), Medium Decliner (7.7%), Mid-High Maintainer (22.8%), and High
      Maintainer (57.5%). Cross-classification of the groups of trajectories
      demonstrated that the impact of a high and stable EF on PSF might be greater than
      the reverse. Low depression symptoms, low pain, and high social support were the
      most consistent predictors of high EF trajectories. CONCLUSION: Aging women are
      heterogeneous in terms of positive aging indicators for up to 9 years of follow
      up. Interventions aimed at promoting sustainable EF might have diffused effects
      on other domains of healthy aging.

PMID- 24739219
TI  - Risk stratification and prognostic performance of the predisposition, infection,
      response, and organ dysfunction (PIRO) scoring system in septic patients in the
      emergency department: a cohort study.
AB  - INTRODUCTION: The predisposition, infection, response and organ dysfunction
      (PIRO) staging system was designed as a stratification tool to deal with the
      inherent heterogeneity of septic patients. The present study was conducted to
      assess the performance of PIRO in predicting multiple organ dysfunction (MOD),
      intensive care unit (ICU) admission, and 28-day mortality in septic patients in
      the emergency department (ED), and to compare this scoring system with the
      Mortality in Emergency Department Sepsis (MEDS) and Acute Physiology and Chronic
      Health Evaluation (APACHE II) scores. METHODS: Consecutive septic patients (n =
      680) admitted to the ED of Beijing Chao-Yang Hospital were enrolled. PIRO, MEDS,
      and APACHE II scores were calculated for each patient on ED arrival. Organ
      function was reassessed within 3 days of enrollment. All patients were followed
      up for 28 days. Outcome criteria were the development of MOD within 3 days, ICU
      admission or death within 28 days after enrollment. The predictive ability of the
      four components of PIRO was analyzed separately. Receiver operating
      characteristic (ROC) curve and logistic regression analysis were used to assess
      the prognostic and risk stratification value of the scoring systems. RESULTS:
      Organ dysfunction independently predicted ICU admission, MOD, and 28-day
      mortality, with areas under the ROC curve (AUC) of 0.888, 0.851, and 0.816,
      respectively. The predictive value of predisposition, infection, and response was
      weaker than that of organ dysfunction. A negative correlation was found between
      the response component and MOD, as well as mortality. PIRO, MEDS, and APACHE II
      scores significantly differed between patients who did and did not meet the
      outcome criteria (P < 0.001). PIRO and APACHE II independently predicted ICU
      admission and MOD, but MEDS did not. All three systems were independent
      predictors of 28-day mortality with similar AUC values. The AUC of PIRO was 0.889
      for ICU admission, 0.817 for MOD, and 0.744 for 28-day mortality. The AUCs of
      PIRO were significantly greater than those of APACHE II and MEDS (P < 0.05) in
      predicting ICU admission and MOD. CONCLUSIONS: The study indicates that PIRO is
      helpful for risk stratification and prognostic determinations in septic patients
      in the ED.

PMID- 24739221
TI  - Impact of preoperative fibrinogen concentration on postoperative outcome in
      patients who received dual antiplatelet therapy in proximity to off-pump coronary
      bypass surgery.
AB  - BACKGROUND: Preoperative fibrinogen concentration is associated with increased
      blood loss at the lower end, and with hypercoagulability-related ischemic event
      at the higher end in cardiac patients. We evaluated the influence of preoperative
      fibrinogen concentration on blood loss and outcome in patients who received
      clopidogrel in proximity to off-pump coronary artery bypass surgery (OPCAB).
      METHODS AND RESULTS: Medical records of 538 patients who received clopidogrel
      within 5 days of OPCAB (April 2007 to March 2012) were retrospectively reviewed.
      Perioperative bleeding and composite of morbidity endpoints including myocardial
      infarction were compared in relation to the tertile distribution of the
      fibrinogen concentration. The amount of blood loss was significantly larger in
      the first tertile, whereas the incidence of composite of morbidity endpoints was
      significantly higher in the third tertile. In multivariate analysis for risk
      factors of perioperative blood loss, body mass index and duration of surgery were
      identified as independent risk factors but not the fibrinogen level. And
      hypertension and preoperative fibrinogen level were identified as independent
      risk factors about composite of morbidity. The third tertile was associated with
      a 2-fold increased risk of developing composite of morbidity endpoints.
      CONCLUSIONS: In patients who received dual antiplatelet therapy in proximity to
      OPCAB, increased preoperative fibrinogen concentration could serve as a valuable
      predictor for composite of morbidity endpoints, whereas low fibrinogen
      concentration was not found to be a risk factor of bleeding.

PMID- 24739222
TI  - Invasive coronary microcirculation assessment--current status of index of
      microcirculatory resistance.
AB  - Assessment of the coronary microvasculature in the clinical setting is a key
      issue, given that microvascular dysfunction itself has a predictive value for
      cardiovascular events. The index of microcirculatory resistance (IMR) is an
      invasive method of interrogating the microvasculature and provides further
      insight into the physiology of cardiovascular diseases. It is simple and readily
      applicable in the cardiac catheterization laboratory where many patients first
      present for evaluation of their coronary circulation. In contrast to other
      invasive and non-invasive tests, this method is known to be stable and
      reproducible under various hemodynamics and even in the presence of epicardial
      coronary artery stenosis. IMR has been shown to have prognostic value in patients
      with ST-segment elevation myocardial infarction; therefore it can be a surrogate
      marker of cardiovascular events. At the same time, it has the potential to be a
      therapeutic as well as an investigational tool in the physiology of
      cardiovascular diseases. This review summarizes the development of IMR, tips and
      tricks for its measurement, and its usefulness in various clinical settings.

PMID- 24739220
TI  - Androgen receptor and gene network: Micromechanics reassemble the signaling
      machinery of TMPRSS2-ERG positive prostate cancer cells.
AB  - Prostate cancer is a gland tumor in the male reproductive system. It is a
      multifaceted and genomically complex disease. Transmembrane protease, serine 2
      and v-ets erythroblastosis virus E26 homolog (TMPRSS2-ERG) gene fusions are the
      common molecular signature of prostate cancer. Although tremendous advances have
      been made in unraveling various facets of TMPRSS2-ERG-positive prostate cancer,
      many research findings must be sequentially collected and re-interpreted. It is
      important to understand the activation or repression of target genes and proteins
      in response to various stimuli and the assembly in signal transduction in TMPRSS2
      ERG fusion-positive prostate cancer cells. Accordingly, we divide this multi
      component review ofprostate cancer cells into several segments: 1) The role of
      TMPRSS2-ERG fusion in genomic instability and methylated regulation in prostate
      cancer and normal cells; 2) Signal transduction cascades in TMPRSS2-ERG fusion
      positive prostate cancer; 3) Overexpressed genes in TMPRSS2-ERG fusion-positive
      prostate cancer cells; 4) miRNA mediated regulation of the androgen receptor (AR)
      and its associated protein network; 5) Quantitative control of ERG in prostate
      cancer cells; 6) TMPRSS2-ERG encoded protein targeting; In conclusion, we provide
      a detailed understanding of TMPRSS2-ERG fusion related information in prostate
      cancer development to provide a rationale for exploring TMPRSS2-ERG fusion
      mediated molecular network machinery. 

PMID- 24739223
TI  - Warfarin therapy still survives as an anticoagulation treatment for patients with
      atrial fibrillation.

PMID- 24739224
TI  - High-altitude hypoxia and echocardiographic indices of pulmonary hypertension in
      male and female chickens at adulthood.
AB  - BACKGROUND: By combining the chick embryo model with incubation at high altitude
      (HA), the effects of chronic hypoxia on fetal growth, fetal cardiac and aortic
      wall remodeling and systemic arterial blood pressure at adulthood were reported.
      Using non-invasive functional echocardiography, here we investigated the in vivo
      effects of HA hypoxia on the pulmonary circulation at adulthood in male and
      female chickens. METHODS AND RESULTS: Chick embryos were incubated, hatched and
      raised at sea level (SL) or at HA. At 6 months of age, functional
      echocardiography was performed and the body and heart weights were taken. Heart
      weight was heavier in males but not in female HA chickens compared to their same
      sex SL counterparts. Similarly, male but not female HA chickens had greater in
      vivo right ventricular wall thickness compared to their same sex SL counterparts.
      The tricuspid pressure gradient was greatly enhanced in HA male and HA female
      chickens. However, the increment in the tricuspid pressure gradient was greater
      in HA males than in HA females. The pulmonary artery diameter was also enhanced
      in HA males than in SL males. In contrast, HA did not affect this variable in
      female chickens. CONCLUSIONS: The data show that chronic hypoxia during
      development at HA is associated with echocardiocraphic indices of pulmonary
      hypertension at adulthood in a highly sex-dependent manner.

PMID- 24739225
TI  - Daily versus intermittent inhaled corticosteroid treatment for mild persistent
      asthma.
AB  - PURPOSE OF REVIEW: Guidelines recommend the use of daily inhaled corticosteroids
      as preferred treatment for preschoolers, children, adolescents, and adults with
      recurrent wheezing and mild persistent asthma. However, intermittent or as-needed
      inhaled corticosteroids treatment in response to symptoms is an emerging
      strategy. This review is focused on the analysis (clinical efficacy and safety)
      of this approach in comparison with the current daily-based therapy. RECENT
      FINDINGS: Recently, some authors favored the use of inhaled corticosteroids based
      on symptoms. It has been suggested that a symptom-based approach could reduce the
      amount of drug used, minimize the risk of adverse events, and reduce healthcare
      costs. In contrast, physicians prescribing intermittent inhaled corticosteroids
      would give the wrong message to their patients about the chronicity of the
      disease. Currently, there is a significant body of high-quality clinical studies
      and systematic reviews that have addressed this important controversy, and whose
      analysis allows us to extract some important conclusions. SUMMARY: Present
      evidence does not support a change in the direction of an intermittent or symptom
      based use approach for recurrent wheezing and mild-to-moderate persistent asthma.
      At this point, there is no convincing basis to alter the current strategy to
      inhaled corticosteroids dosing, and more studies are needed comparing these two
      approaches.

PMID- 24739226
TI  - Individual pollen exposure measurements: are they feasible?
AB  - PURPOSE OF REVIEW: The purpose of the recent review is to give insight into
      recent attempts to measure individual pollen exposure and to give advice for
      interpreting such data. RECENT FINDINGS: It is well recognized that there are
      various challenges in monitoring the atmospheric content of pollen in the air.
      Although pollen data gathered by Hirst type spore traps and evaluated by human
      expertise are of inestimable value because of long-time data series and as the
      basic foundation for pollen information services as well as for diagnosis and
      therapy of pollen allergies, there is a need for more precise information for
      individual pollen allergy sufferers. Different types of individual pollen
      exposure measurement samplers are presented, and estimates are offered. SUMMARY:
      Further developments, especially standardization of personal pollen samplers, are
      needed. Improvements should lead to more usability. Because of a variety of
      factors, a pollen count will always stay a pollen count, and a pollen forecast is
      not a symptom forecast, something pollen allergy sufferers actually desire. Thus,
      a different promising path to individualized pollen information was recently
      chosen: personal pollen information is now possible based on personal symptom
      data and regional pollen data. In future, personal pollen data could complete
      this achievement.

PMID- 24739227
TI  - Differential diagnosis of food protein-induced enterocolitis syndrome.
AB  - PURPOSE OF REVIEW: To assess all the possible differential diagnosis of food
      protein-induced enterocolitis syndrome (FPIES), both in acute and chronic
      presentation, reviewing the data reported in published studies. RECENT FINDINGS:
      There is an increase of reported cases of FPIES in recent years. As the disease
      presents with nonspecific symptoms, it can be misunderstood in many ways. The
      differential diagnosis includes, in acute presentations, the following: sepsis,
      other infectious diseases, acute gastrointestinal episodes, surgical emergencies,
      food allergies. In its chronic forms, FPIES may mimic malabsorption syndromes,
      metabolic disorders, primary immunodeficiencies, neurological conditions,
      coagulation defects, and other types of non-IgE-mediated food allergy. SUMMARY: A
      thorough clinical evaluation, including symptoms, signs, and laboratory findings,
      is necessary to lead the clinicians toward the diagnosis of FPIES. The major
      reason for delayed diagnosis appears to be the lack of knowledge of the disease.

PMID- 24739228
TI  - Single-stage internal fixation for thoracolumbar spinal tuberculosis using 4
      different surgical approaches.
AB  - STUDY DESIGN: A retrospective study was conducted on 148 spinal tuberculosis (TB)
      patients (M:F, 92:56; mean age, 39.7+/-12.3; range, 16-74 y) treated with
      anterior debridement and bone graft fusion with nail and screw internal fixation
      (nails+screws group); posterior pedicle screw fixation (pedicle screw group);
      vertebral arch pedicle internal fixation through a posterior route (posterior
      arch fixation group); or posterior debridement, bone graft fusion, and vertebral
      arch pedicle internal fixation (arch fixation group). OBJECTIVE: We investigated
      4 variant surgical approaches for internal fixation of spinal TB. SUMMARY OF
      BACKGROUND DATA: The effectiveness of single-stage surgical fixation for
      different degrees of spinal TB is a matter of debate. METHODS: Operation time and
      bleeding volume were recorded. Complications, American Spinal Injury Association
      (ASIA) score, C-reactive protein, and erythrocyte sedimentation rate were
      examined preoperatively and 6 months after surgery. RESULTS: Overall, 78, 48, 16,
      and 6 patients underwent nails+screws, pedicle screws, arch fixation, and
      posterior arch fixation approaches, respectively. The mean operation times were
      175.8+/-48.8, 308.5+/-76.7, 143.8+/-43.0, and 398.3+/-90.8, respectively
      (P<0.01). Mean blood transfusion volumes were 1227.1+/-988.2, 1771.7+/-794.7,
      467.7+/-123.3, and 2833.3+/-1083.8 mL, respectively (P<0.01). Primary wound
      healing was achieved in 127 patients. No patients experienced spinal TB
      recurrence or failure of bone graft or fixation. All groups achieved
      significantly improved C-reactive protein and erythrocyte sedimentation rate, but
      significantly improved ASIA scores were only observed in the nails+screws and
      pedicle screw groups (P<0.01). CONCLUSIONS: Surgical approach limitations and
      advantages should be considered based on the position and severity of spinal TB
      infection to maximize functional outcomes and minimize surgical risks.

PMID- 24739230
TI  - Analysis of variation for apomictic reproduction in diploid Paspalum rufum.
AB  - BACKGROUND AND AIMS: The diploid cytotype of Paspalum rufum (Poaceae) reproduces
      sexually and is self-sterile; however, recurrent autopolyploidization through 2n
      + n fertilization and the ability for reproduction via apomixis have been
      documented in one genotype of the species. The objectives of this work were to
      analyse the variation in the functionality of apomixis components in diploid
      genotypes of P. rufum and to identify individuals with contrasting reproductive
      behaviours. METHODS: Samples of five individuals from each of three natural
      populations of P. rufum (designated R2, R5 and R6) were used. Seeds were obtained
      after open pollination, selfing, conspecific interploidy crosses and
      interspecific interploidy self-pollination induction. The reproductive behaviour
      of each plant was determined by using the flow cytometric seed screen (FCSS)
      method. Embryo sacs were cleared using a series of ethanol and methyl salicylate
      solutions and observed microscopically. KEY RESULTS: In open pollination, all
      genotypes formed seeds by sexual means and no evidence of apomeiotic reproduction
      was detected. However, in conspecific interploidy crosses and interspecific
      interploidy self-pollination induction, variations in the reproductive pathways
      were observed. While all plants from populations R2 and R6 formed seeds
      exclusively by sexual means, three genotypes from the R5 population developed
      seeds from both meiotic and aposporous embryo sacs, and one of them (R5#49)
      through the complete apomictic pathway (apospory + parthenogenesis + pseudogamy).
      Cytoembryological observations revealed the presence of both meiotic and
      aposporous embryo sacs in all the genotypes analysed, suggesting that
      parthenogenesis could be uncoupled from apospory in some genotypes. CONCLUSIONS:
      The results presented demonstrate the existence of variation in the functionality
      of apomixis components in natural diploid genotypes of P. rufum and have
      identified individuals with contrasting reproductive behaviours. Genotypes
      identified here can be crossed to generate segregating populations in order to
      study apomixis determinants at the diploid level. Moreover, analysis of their
      expression patterns, quantification of their transcript levels and an
      understanding of their regulation mechanisms could help to design new strategies
      for recreating apomixis in a diploid genome environment.

PMID- 24739231
TI  - Response to Dr Kintz's letter.

PMID- 24739232
TI  - Sexually different physiological responses of Populus cathayana to nitrogen and
      phosphorus deficiencies.
AB  - Previous studies have shown that there are significant sexual differences in the
      morphological and physiological responses of Populus cathayana Rehder under
      stressful conditions. However, little is known about sex-specific differences in
      responses to nutrient deficiencies. In this study, the effects of nitrogen (N)
      and phosphorus (P) deficiencies on the morphological, physiological and
      chloroplast ultrastructural traits of P. cathayana males and females were
      investigated. The results showed that N and P deficiencies significantly
      decreased plant growth, foliar N and P contents, chlorophyll content,
      photosynthesis, and instantaneous photosynthetic N- and P-use efficiencies (PNUE
      and PPUE) in both sexes. Males had higher photosynthesis, higher PNUE and PPUE
      rates, and a lower accumulation of plastoglobules in chloroplasts than did
      females when exposed to N- and P-deficiency conditions. Nitrogen-deficient males
      had higher glutamate dehydrogenase and peroxidase activities, and a more intact
      chloroplast ultrastructure, but less starch accumulation than did N-deficient
      females. Phosphorus-deficient males had higher nitrate reductase, glutamine
      synthetase and acid phosphatase activities, but a lower foliar N : P ratio and
      less PSII damage than did P-deficient females. These results suggest that N and P
      deficiencies cause greater negative effects on females than on males, and that
      the different sexes of P. cathayana may employ different strategies to cope with
      N and P deficiencies. 

PMID- 24739233
TI  - Cannabis use in first-treatment bipolar I disorder: relations to clinical
      characteristics.
AB  - AIMS: The aim of this study was to investigate the associations between recent
      cannabis use, current symptomatology and age at onset of first manic, depressive
      and psychotic episodes in a large sample with first-treatment bipolar I disorder
      (BD I). METHODS: One hundred one patients with first-treatment Diagnostic and
      Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) bipolar I
      disorder were included as part of the Thematically Organized Psychosis study. The
      Structural Clinical Interview for DSM-IV was used for DSM-IV diagnosis and
      identification of episodes of illness. Earlier suicide attempts were recorded.
      Manic, depressive and psychotic symptoms were rated using the Young Mania Rating
      Scale, Inventory of Depressive Symptoms and Positive and Negative Syndrome Scale
      correspondingly. Cannabis use within the six last months was recorded. RESULTS:
      After controlling for confounders, recent cannabis use was significantly
      associated with lower age at onset of first manic and psychotic episode, but not
      with onset of first depressive episode (both P < 0.05). Recent use was also
      associated with more lifetime suicide attempts (P < 0.01). No group differences
      were found on symptom levels. CONCLUSIONS: The present study confirms earlier
      findings of an association between cannabis use and a lower age at onset. Recent
      cannabis use was also associated with more lifetime suicide attempts. The current
      findings suggest that recent cannabis use is associated with a more severe course
      of illness in the early phase of BD I.

PMID- 24739234
TI  - Foot force direction control during a pedaling task in individuals post-stroke.
AB  - BACKGROUND: Appropriate magnitude and directional control of foot-forces is
      required for successful execution of locomotor tasks. Earlier evidence suggested,
      following stroke, there is a potential impairment in foot-force control
      capabilities both during stationary force generation and locomotion. The purpose
      of this study was to investigate the foot-pedal surface interaction force
      components, in non-neurologically-impaired and stroke-impaired individuals, in
      order to determine how fore/aft shear-directed foot/pedal forces are controlled.
      METHODS: Sixteen individuals with chronic post-stroke hemiplegia and 10 age
      similar non-neurologically-impaired controls performed a foot placement
      maintenance task under a stationary and a pedaling condition, achieving a target
      normal pedal force. Electromyography and force profiles were recorded. We
      expected generation of unduly large magnitude shear pedal forces and reduced
      participation of multiple muscles that can contribute forces in appropriate
      directions in individuals post-stroke. RESULTS: We found lower force output,
      inconsistent modulation of muscle activity and reduced ability to change foot
      force direction in the paretic limbs, but we did not observe unduly large
      magnitude shear pedal surface forces by the paretic limbs as we hypothesized.
      CONCLUSION: These findings suggested the preservation of foot-force control
      capabilities post-stroke under minimal upright postural control requirements.
      Further research must be conducted to determine whether inappropriate shear force
      generation will be revealed under non-seated, postural demanding conditions,
      where subjects have to actively control for upright body suspension.

PMID- 24739235
TI  - Does access to a colorectal cancer screening website and/or a nurse-managed
      telephone help line provided to patients by their family physician increase fecal
      occult blood test uptake?: results from a pragmatic cluster randomized controlled
      trial.
AB  - BACKGROUND: Evaluation of the effectiveness of a patient decision aid (nurse
      managed telephone support line and/or colorectal cancer screening website),
      distributed to patients by their family physician, in improving fecal occult
      blood test (FOBT) colorectal cancer screening rates. METHODS: A pragmatic, two
      arm, cluster randomized controlled trial in Winnipeg, Manitoba, Canada (39
      medical clinic clusters; 79 fee-for-service family physicians; 2,395 average risk
      patients). All physicians followed their standard clinical screening practice.
      Intervention group physicians provided a fridge magnet to patients that
      facilitated patient decision aid access. Primary endpoint was FOBT screening rate
      within four months.Multi-level logistic regression to determine effect of
      cluster, physician, and patient level factors on patient FOBT completion rate.
      ICC determined. RESULTS: Family physicians were randomized to control (n = 39)
      and intervention (n = 40) groups. Compared to controls (56.9%; n = 663/1165),
      patients receiving the intervention had a higher FOBT completion rate (66.6%; n =
      805/1209; OR of 1.47; 95% confidence interval 1.06 to 2.03; p < 0.02). Patient
      aid utilization was low (1.1%; 13/1,221) and neither internet nor telephone
      access affected screening rates for the intervention group. FOBT screening rates
      differed among clinics and physicians (p < 0.0001). Patients whose physician
      promoted the FOBT were more likely to complete it (65%; n = 1140/1755) compared
      to those whose physician did not (51.1%; n = 242/470; p < 0.0001; OR of 1.54 and
      95% CI of 1.23 to 1.92). Patients reporting they had done an FOBT in the past
      were more likely to complete the test (70.6%; n = 1141/1616; p < 0.0001; 95% CI
      2.51 to 3.73) than those who had not (43%; n = 303/705). Patients 50-59 years old
      had lower screening rates compared to those over 60 (p < 0.0001). 75% of patients
      completing the test did so in 34 days. CONCLUSION: Despite minimal use of the
      patient aid, intervention group patients were more likely to complete the FOBT.
      Powerful strategies to increase colorectal cancer screening rates include a
      recommendation to do the test from the family physician and focusing efforts on
      patients age 50-59 years to ensure they complete their first FOBT. TRIAL
      REGISTRATION:  TRIAL REGISTRATION NUMBER: clinicaltrials.gov identifier
      NCT01026753.

PMID- 24739236
TI  - Adjustment of microbial nitrogen use efficiency to carbon:nitrogen imbalances
      regulates soil nitrogen cycling.
AB  - Microbial nitrogen use efficiency (NUE) describes the partitioning of organic N
      taken up between growth and the release of inorganic N to the environment (that
      is, N mineralization), and is thus central to our understanding of N cycling.
      Here we report empirical evidence that microbial decomposer communities in soil
      and plant litter regulate their NUE. We find that microbes retain most
      immobilized organic N (high NUE), when they are N limited, resulting in low N
      mineralization. However, when the metabolic control of microbial decomposers
      switches from N to C limitation, they release an increasing fraction of organic N
      as ammonium (low NUE). We conclude that the regulation of NUE is an essential
      strategy of microbial communities to cope with resource imbalances, independent
      of the regulation of microbial carbon use efficiency, with significant effects on
      terrestrial N cycling. 

PMID- 24739237
TI  - Integrative analyses of genetic variation, epigenetic regulation, and the
      transcriptome to elucidate the biology of platinum sensitivity.
AB  - BACKGROUND: Using genome-wide genetic, gene expression, and microRNA expression
      (miRNA) data, we developed an integrative approach to investigate the genetic and
      epigenetic basis of chemotherapeutic sensitivity. RESULTS: Through a sequential
      multi-stage framework, we identified genes and miRNAs whose expression correlated
      with platinum sensitivity, mapped these to genomic loci as quantitative trait
      loci (QTLs), and evaluated the associations between these QTLs and platinum
      sensitivity. A permutation analysis showed that top findings from our approach
      have a much lower false discovery rate compared to those from a traditional GWAS
      of drug sensitivity. Our approach identified five SNPs associated with 10 miRNAs
      and the expression level of 15 genes, all of which were associated with
      carboplatin sensitivity. Of particular interest was one SNP (rs11138019), which
      was associated with the expression of both miR-30d and the gene ABCD2, which were
      themselves correlated with both carboplatin and cisplatin drug-specific phenotype
      in the HapMap samples. Functional study found that knocking down ABCD2 in vitro
      led to increased apoptosis in ovarian cancer cell line SKOV3 after cisplatin
      treatment. Over-expression of miR-30d in vitro caused a decrease in ABCD2
      expression, suggesting a functional relationship between the two. CONCLUSIONS: We
      developed an integrative approach to the investigation of the genetic and
      epigenetic basis of human complex traits. Our approach outperformed standard GWAS
      and provided hints at potential biological function. The relationships between
      ABCD2 and miR-30d, and ABCD2 and platin sensitivity were experimentally
      validated, suggesting a functional role of ABCD2 and miR-30d in sensitivity to
      platinating agents.

PMID- 24739238
TI  - Isolation, in silico characterization, localization and expression analysis of
      abiotic stress-responsive rice G-protein beta subunit (RGB1).
AB  - Heterotrimeric G-proteins constitute the classical signaling paradigm along with
      their cognate G-protein coupled receptors (GPCRs) and appropriate downstream
      effectors. G-protein complex is composed of highly conserved Galpha, Gbeta, and
      Ggamma subunits. In the present study, we have characterized the cis-regulatory
      elements of the promoter, signature motifs, transcript profile in response to
      abiotic stresses, and sub-cellular localization of G-protein beta subunit RGB1(I)
      from Indica rice. The RGB1(I) promoter sequence has various stress-related cis
      regulatory elements suggesting its role in abiotic stress signaling. Presence of
      six WD-40 repeat signature motifs in RGB1(I) suggest its role in exchange of GDP
      by GTP in Galpha subunit and receptor recognition. Presence of multiple N
      myristoylation consensus sites in RGB1(I) protein sequence, which is necessary
      for membrane localization of protein, confirms the association of RGB1(I) in
      plasma membrane. Extrinsic association of RGB1(I) with plasma membrane seems
      essential for its role in regulation of signaling pathways and adaptation to high
      salt stress. We report the sub-cellular localization of RGB1(I) in plasma
      membrane, cytosol and nucleus. The localization of RGB1(I) in nucleus supports
      its possible interaction with transcription factors regulating the expression of
      salt stress responsive genes. The RGB1(I) transcript was upregulated under KCl,
      cold, dehydration and micronutrient (Mn (2+) and Zn (2+)) stress. However,
      transcript variation under elevated temperature, ABA, NaCl, and toxic heavy
      metals (viz. arsenite, arsenate, cadmium and lead) was not encouraging. These
      evidences indicate an active and significant role of RGB1(I) in the regulation of
      abiotic stresses in rice and propound its possible exploitation in the
      development of abiotic stress tolerance in crops. 

PMID- 24739239
TI  - The direct and indirect costs of both overweight and obesity: a systematic
      review.
AB  - BACKGROUND: The rising prevalence of overweight and obesity places a financial
      burden on health services and on the wider economy. Health service and societal
      costs of overweight and obesity are typically estimated by top-down approaches
      which derive population attributable fractions for a range of conditions
      associated with increased body fat or bottom-up methods based on analyses of
      cross-sectional or longitudinal datasets. The evidence base of cost of obesity
      studies is continually expanding, however, the scope of these studies varies
      widely and a lack of standardised methods limits comparisons nationally and
      internationally. The objective of this review is to contribute to this knowledge
      pool by examining direct costs and indirect (lost productivity) costs of both
      overweight and obesity to provide comparable estimates. This review was
      undertaken as part of the introductory work for the Irish cost of overweight and
      obesity study and examines inconsistencies in the methodologies of cost of
      overweight and obesity studies. Studies which evaluated the direct costs and
      indirect costs of both overweight and obesity were included. METHODS: A
      computerised search of English language studies addressing direct and indirect
      costs of overweight and obesity in adults between 2001 and 2011 was conducted.
      Reference lists of reports, articles and earlier reviews were scanned to identify
      additional studies. RESULTS: Five published articles were deemed eligible for
      inclusion. Despite the limited scope of this review there was considerable
      heterogeneity in methodological approaches and findings. In the four studies
      which presented separate estimates for direct and indirect costs of overweight
      and obesity, the indirect costs were higher, accounting for between 54% and 59%
      of the estimated total costs. CONCLUSION: A gradient exists between increasing
      BMI and direct healthcare costs and indirect costs due to reduced productivity
      and early premature mortality. Determining precise estimates for the increases is
      mired by the large presence of heterogeneity among the available cost estimation
      literature. To improve the availability of quality evidence an international
      consensus on standardised methods for cost of obesity studies is warranted.
      Analyses of nationally representative cross-sectional datasets augmented by data
      from primary care are likely to provide the best data for international
      comparisons.

PMID- 24739240
TI  - Characterization of a functionally active recombinant 1-deoxy-D-xylulose-5
      phosphate synthase from Babesia bovis.
AB  - The 1-deoxy-D-xylulose-5-phosphate synthase (DXS) enzyme has been characterized
      in other species, but not in the genus Babesia, which causes major losses in the
      livestock industries worldwide. Therefore, we isolated, cloned and expressed the
      wild-type B. bovis dxs cDNA in Escherichia coli and evaluated its enzymatic
      activity in vitro. DNA sequence analysis revealed an open reading frame of 2061
      bp capable of encoding a polypeptide of 686 amino acid residues with a calculated
      isoelectric point of pH 6.93 and a molecular mass of 75 kDa. The expressed
      soluble recombinant fusion DXS protein was approximately 78 kDa, which is similar
      to the native enzyme identified from the parasite merozoite using anti-rDXS
      serum. The recombinant fusion DXS enzyme exhibited Km values of 380 +/- 46 uM and
      790 +/- 52 uM for D,L-glyceraldehyde 3-phosphate and pyruvate, respectively. In
      this work, we present the first cloning, expression and characterization of DXS
      enzyme from B. bovis. 

PMID- 24739242
TI  - Palliative and end-of-life care should not be last or least.

PMID- 24739241
TI  - Transcriptional dissection of pancreatic tumors engrafted in mice.
AB  - BACKGROUND: Engraftment of primary pancreas ductal adenocarcinomas (PDAC) in mice
      to generate patient-derived xenograft (PDX) models is a promising platform for
      biological and therapeutic studies in this disease. However, these models are
      still incompletely characterized. Here, we measured the impact of the murine
      tumor environment on the gene expression of the engrafted human tumoral cells.
      METHODS: We have analyzed gene expression profiles from 35 new PDX models and
      compared them with previously published microarray data of 18 PDX models, 53
      primary tumors and 41 cell lines from PDAC. The results obtained in the PDAC
      system were further compared with public available microarray data from 42 PDX
      models, 108 primary tumors and 32 cell lines from hepatocellular carcinoma (HCC).
      We developed a robust analysis protocol to explore the gene expression space. In
      addition, we completed the analysis with a functional characterization of PDX
      models, including if changes were caused by murine environment or by serial
      passing. RESULTS: Our results showed that PDX models derived from PDAC, or HCC,
      were clearly different to the cell lines derived from the same cancer tissues.
      Indeed, PDAC- and HCC-derived cell lines are indistinguishable from each other
      based on their gene expression profiles. In contrast, the transcriptomes of PDAC
      and HCC PDX models can be separated into two different groups that share some
      partial similarity with their corresponding original primary tumors. Our results
      point to the lack of human stromal involvement in PDXs as a major factor
      contributing to their differences from the original primary tumors. The main
      functional differences between pancreatic PDX models and human PDAC are the lower
      expression of genes involved in pathways related to extracellular matrix and
      hemostasis and the up- regulation of cell cycle genes. Importantly, most of these
      differences are detected in the first passages after the tumor engraftment.
      CONCLUSIONS: Our results suggest that PDX models of PDAC and HCC retain, to some
      extent, a gene expression memory of the original primary tumors, while this
      pattern is not detected in conventional cancer cell lines. Expression changes in
      PDXs are mainly related to pathways reflecting the lack of human infiltrating
      cells and the adaptation to a new environment. We also provide evidence of the
      stability of gene expression patterns over subsequent passages, indicating early
      phases of the adaptation process.

PMID- 24739243
TI  - Luis Velazquez-Perez: helping to put SCA2 in the spotlight.

PMID- 24739244
TI  - Tackling ataxia.

PMID- 24739248
TI  - New approaches to obstetric hemorrhage: the postpartum hemorrhage consensus
      algorithm.
AB  - PURPOSE OF REVIEW: Postpartum hemorrhage is increasingly frequent and a major
      contributor to maternal morbidity and mortality. Although individual steps, such
      as coagulation or surgical management, have been reviewed, there is little
      information on treatment algorithms. RECENT FINDINGS: A treatment algorithm for
      postpartum hemorrhage was developed by the experts from three different
      specialties and from three countries. The algorithm describes symptoms,
      diagnosis, general measurements, medication, and organizational aspects. SUMMARY:
      The algorithm is thought to serve as a template for local adaptation. It will
      hopefully improve the management of postpartum hemorrhage.

PMID- 24739249
TI  - Quantifying severe maternal morbidity in Scotland: a continuous audit since 2003.
AB  - Since 2003, a continuous audit of severe maternal morbidity in Scotland has been
      conducted, collecting data on consistently defined events in all the consultant
      led maternity units within Scotland. This review summarizes the methodology of
      the audit and describes some of the main results accumulated in the 10 years
      audited [2003-2012 (The 2012 Scottish Confidential Audit of Severe Maternal
      Morbidity report is yet to be published. This article refers to extracts from
      2012 data where available, but on other occasions refers to data from 2003 to
      2011.)]. Although most causes of severe maternal morbidity have decreased during
      the audit, major obstetric haemorrhage, the most common cause of severe maternal
      morbidity, has increased. Some key findings are as follows: admission to an ICU
      is required for 1 woman in every 700 births; major obstetric haemorrhage is
      experienced by 1 in 172 women; cases of eclampsia have decreased during the
      audit; there were deficiencies in antenatal risk identification and action
      planning; and the direct involvement of consultant obstetricians and
      anaesthetists in the care of women was below those recommended by the guidelines.
      The audit has demonstrated changes in clinical practice and in adherence to
      clinical guidelines over time. The information has been used to inform clinical
      practice within the Scottish maternity units. 

PMID- 24739247
TI  - In vivo immunogenicity of Tax(11-19) epitope in HLA-A2/DTR transgenic mice:
      implication for dendritic cell-based anti-HTLV-1 vaccine.
AB  - Viral oncoprotein Tax plays key roles in transformation of human T-cell leukemia
      virus (HTLV-1)-infected T cells leading to adult T-cell leukemia (ATL), and is
      the key antigen recognized during HTLV-associated myelopathy (HAM). In HLA-A2+
      asymptomatic carriers as well as ATL and HAM patients, Tax(11-19) epitope
      exhibits immunodominance. Here, we evaluate CD8 T-cell immune response against
      this epitope in the presence and absence of dendritic cells (DCs) given the
      recent encouraging observations made with Phase 1 DC-based vaccine trial for ATL.
      To facilitate these studies, we first generated an HLA-A2/DTR hybrid mouse strain
      carrying the HLA-A2.1 and CD11c-DTR genes. We then studied CD8 T-cell immune
      response against Tax(11-19) epitope delivered in the absence or presence of
      Freund's adjuvant and/or DCs. Overall results demonstrate that naturally
      presented Tax epitope could initiate an antigen-specific CD8T cell response in
      vivo but failed to do so upon DC depletion. Presence of adjuvant potentiated
      Tax(11-19)-specific response. Elevated serum IL-6 levels coincided with depletion
      of DCs whereas decreased TGF-beta was associated with adjuvant use. Thus, Tax(11
      19) epitope is a potential candidate for the DC-based anti-HTLV-1 vaccine and the
      newly hybrid mouse strain could be used for investigating DC involvement in human
      class-I-restricted immune responses. 

PMID- 24739246
TI  - Distinct neurological disorders with ATP1A3 mutations.
AB  - Genetic research has shown that mutations that modify the protein-coding sequence
      of ATP1A3, the gene encoding the alpha3 subunit of Na(+)/K(+)-ATPase, cause both
      rapid-onset dystonia parkinsonism and alternating hemiplegia of childhood. These
      discoveries link two clinically distinct neurological diseases to the same gene,
      however, ATP1A3 mutations are, with one exception, disease-specific. Although the
      exact mechanism of how these mutations lead to disease is still unknown, much
      knowledge has been gained about functional consequences of ATP1A3 mutations using
      a range of in-vitro and animal model systems, and the role of Na(+)/K(+)-ATPases
      in the brain. Researchers and clinicians are attempting to further characterise
      neurological manifestations associated with mutations in ATP1A3, and to build on
      the existing molecular knowledge to understand how specific mutations can lead to
      different diseases. 

PMID- 24739250
TI  - Comparison of an assumed versus measured leucocyte count in parasite density
      calculations in Papua New Guinean children with uncomplicated malaria.
AB  - BACKGROUND: The accuracy of the World Health Organization method of estimating
      malaria parasite density from thick blood smears by assuming a white blood cell
      (WBC) count of 8,000/MUL has been questioned in several studies. Since
      epidemiological investigations, anti-malarial efficacy trials and routine
      laboratory reporting in Papua New Guinea (PNG) have all relied on this approach,
      its validity was assessed as part of a trial of artemisinin-based combination
      therapy, which included blood smear microscopy and automated measurement of
      leucocyte densities on Days 0, 3 and 7. RESULTS: 168 children with uncomplicated
      malaria (median (inter-quartile range) age 44 (39-47) months) were enrolled,
      80.3% with Plasmodium falciparum monoinfection, 14.9% with Plasmodium vivax
      monoinfection, and 4.8% with mixed P. falciparum/P. vivax infection. All
      responded to allocated therapy and none had a malaria-positive slide on Day 3.
      Consistent with a median baseline WBC density of 7.3 (6.5-7.8) * 10(9)/L, there
      was no significant difference in baseline parasite density between the two
      methods regardless of Plasmodium species. Bland Altman plots showed that, for
      both species, the mean difference between paired parasite densities calculated
      from assumed and measured WBC densities was close to zero. At parasite densities
      <10,000/MUL by measured WBC, almost all between-method differences were within
      the 95% limits of agreement. Above this range, there was increasing scatter but
      no systematic bias. CONCLUSIONS: Diagnostic thresholds and parasite clearance
      assessment in most PNG children with uncomplicated malaria are relatively robust,
      but accurate estimates of a higher parasitaemia, as a prognostic index, requires
      formal WBC measurement.

PMID- 24739251
TI  - The development and implementation of a pilot CBT for early psychosis service:
      achievements and challenges.
AB  - AIM: Cognitive behaviour therapy (CBT) is a clinically indicated treatment for
      first-episode psychosis. Despite this, CBT for early psychosis is not routinely
      available as part of standard mental health services in Australia. The aim of
      this pilot project was to develop a CBT for early psychosis service to be
      provided as an adjunct to existing community mental health services. This study
      examined the feasibility of this service model, delivered in a real-world
      setting. A secondary aim was to explore the effectiveness of this service, as
      measured by clinical and functional outcomes. METHODS: Participants living in
      northern Sydney, Australia, and who had recently experienced a first episode of
      psychosis, were offered up to 20 sessions of individual CBT. Service feasibility
      was measured via attrition rates, therapy attendance and referrer feedback.
      Measures of psychosis, depression, anxiety and psychosocial functioning, were
      assessed pretreatment, after six and 12 sessions, and at 3 months post-treatment.
      RESULTS: Nineteen clients attended treatment to completion. Survey feedback from
      referrers affirmed the positive impact of the service on clients' recovery.
      Additionally, clients showed improvements in symptoms of psychosis over the first
      three time points. Psychosocial functioning also shifted from the moderately to
      mildly impaired range by the end of treatment. CONCLUSIONS: The CBT for early
      psychosis service has been successfully integrated into the mental health
      landscape of northern Sydney. Outcomes of this pilot project are discussed with
      reference to the achievements of the service, as well as the obstacles
      encountered, and how they were overcome.

PMID- 24739252
TI  - Motivations for avoiding wheat consumption in Australia: results from a
      population survey.
AB  - OBJECTIVE: To assess the prevalence of and explanations for wheat avoidance,
      including reported symptoms, diagnoses and information sources influencing the
      decision to avoid wheat, and to investigate potential psychological predictors of
      this behaviour. DESIGN: Cross-sectional population survey. SETTING: The study was
      conducted in Australia, using a nationwide postal omnibus survey. SUBJECTS:
      Adults aged 18 years and over (n 1184; 52.9% female) selected at random from the
      Australian Electoral Roll. RESULTS: With cases of stated and suspected coeliac
      disease (1.2%) excluded, 7.3% of the sample reported adverse physiological
      effects, predominantly gastrointestinal, that they associated with wheat
      consumption. Few among this group (5.7%) claimed a formally diagnosed intolerance
      or allergy requiring avoidance of wheat-based foods. Symptomatic wheat avoidance
      was highly correlated with dairy avoidance and predicted by gender (female),
      lesser receptiveness to conventional medicine and greater receptiveness to
      complementary medicine, but not by neuroticism, reasoning style or tendency to
      worry about illness. CONCLUSIONS: The data indicate that many adult Australians
      are consciously avoiding consumption of wheat foods, predominantly without any
      formal diagnosis. Reported symptoms suggest a physiological but not allergenic
      basis to this behaviour. Questions to be answered concern whether symptoms are
      attributed correctly to wheat, the agents (wheat components, dietary factors or
      additives) and physiological mechanism(s) involved, the nutritional adequacy of
      avoiders' diets, and the clinical and psychosocial processes that lead a
      substantial number of adults to avoid consuming wheat (or any other dietary
      factor) apparently independently of a medical diagnosis.

PMID- 24739253
TI  - Arabidopsis thaliana glucuronosyltransferase in family GT14.
AB  - Arabinogalactan proteins are abundant cell-surface proteoglycans in plants and
      are involved in many cellular processes including somatic embryogenesis, cell
      cell interactions, and cell elongation. We reported a glucuronosyltransferase
      encoded by Arabidopsis AtGlcAT14A, which catalyzes an addition of glucuronic acid
      residues to beta-1,3- and beta-1,6-linked galactans of arabinogalactan (Knoch et
      al. 2013). The knockout mutant of this gene resulted in the enhanced growth rate
      of hypocotyls and roots of seedlings, suggesting an involvement of AtGlcAT14A in
      cell elongation. AtGlcAt14A belongs to the family GT14 in the Carbohydrate Active
      Enzyme database (CAZy; www.cazy.org), in which a total of 11 proteins, including
      AtGLCAT14A, are classified from Arabidopsis thaliana. In this paper, we report
      the enzyme activities for the rest of the Arabidopsis GT14 isoforms, analyzed in
      the same way as for AtGlcAT14A. Evidently, two other Arabidopsis GT14 isoforms,
      At5g15050 and At2g37585, also possess the glucuronosyltransferase activity adding
      glucuronic acid residues to beta-1,3- and beta-1,6-linked galactans. Therefore,
      we named At5g15050 and At2g37585 as AtGlcAT14B and AtGlcAT14C, respectively. 

PMID- 24739254
TI  - Pilomatrix carcinoma: 13 new cases and review of the literature with emphasis on
      predictors of metastasis.
AB  - BACKGROUND: Pilomatrix carcinoma is a rare cutaneous tumor derived from
      follicular matrix cells with few cases documented in the literature. OBJECTIVE:
      We sought to better characterize this tumor by analyzing its epidemiologic,
      clinical, and histopathologic features in 13 new cases and by reviewing the
      literature. METHODS: All cases of pilomatrix carcinoma from a large regional
      dermatopathology practice were identified and analyzed by chart review for
      clinical and histopathologic characteristics. Similar characteristics were
      compiled from an additional 123 cases in the English-language literature. Cox
      proportional hazards regression models were used to determine risk factors
      associated with the development of metastasis for all identified metastatic
      tumors. RESULTS: Our 13 tumors were most common in middle-aged to older white men
      and presented mostly on the head/neck. Histopathologically, tumors were
      asymmetric, were poorly circumscribed, were composed of basaloid and "ghost"
      cells, had frequent atypical mitoses, and had infrequent lymphovascular invasion.
      Wide excision was considered the most definitive treatment modality, but local
      recurrence was common. When analyzing all reported cases of metastasis using
      statistics, metastasis was significantly associated (hazard ratio 3.45, P <
      .0413) with local tumor recurrence. LIMITATIONS: The retrospective, single-center
      design and the reliance on electronic medical records are limitations.
      CONCLUSIONS: This study helps better characterize pilomatrix carcinoma and
      identifies potential predictors of metastasis.

PMID- 24739255
TI  - Increasing motivation in robot-aided arm rehabilitation with competitive and
      cooperative gameplay.
AB  - BACKGROUND: Several strategies have been proposed to improve patient motivation
      and exercise intensity during robot-aided stroke rehabilitation. One relatively
      unexplored possibility is two-player gameplay, allowing subjects to compete or
      cooperate with each other to achieve a common goal. In order to explore the
      potential of such games, we designed a two-player game played using two ARMin arm
      rehabilitation robots. METHODS: The game was an air-hockey task displayed on a
      computer monitor and controlled using shoulder movements in the ARMin robot.
      Three game modes were tested: single-player (competing against computer),
      competitive (competing against human), and cooperative (cooperating with human
      against computer). All modes were played by 30 unimpaired subjects and 8 impaired
      chronic stroke subjects. The subjects filled out the Intrinsic Motivation
      Inventory questionnaire after each game mode, as well as a final questionnaire
      about game preferences and their personality. RESULTS: Nearly all unimpaired
      subjects preferred playing the two-player game modes to the single-player one, as
      they enjoyed talking and interacting with another person. However, there were two
      distinct player groups: one liked the competitive mode but not the cooperative
      mode while the other liked the cooperative but not the competitive mode.
      Unimpaired subjects who liked the competitive mode also put significantly more
      effort into it than into the other modes. Results from impaired subjects were
      similar, with even impaired subjects over 60 years old enjoying competitive
      gameplay. The subjects' personalities roughly predicted which mode they would
      prefer, which was especially evident in a poorly-matched impaired pair that
      preferred the single-player mode. CONCLUSIONS: Results indicate great potential
      for two-player rehabilitation games, in the form of greater enjoyment as well as
      potentially more intensive exercise compared to single-player games. However, the
      right game type needs to be chosen for each subject depending on skill and
      personality, along with selecting an appropriate co-player. Further studies with
      patients that are currently enrolled in rehabilitation programs are recommended,
      and the subjective measures used in our study should be augmented with objective
      measures such as electromyography.

PMID- 24739256
TI  - Supersymmetric mode converters.
AB  - Originally developed in the context of quantum field theory, the concept of
      supersymmetry can be used to systematically design a new class of optical
      structures. In this work, we demonstrate how key features arising from optical
      supersymmetry can be exploited to control the flow of light for mode-division
      multiplexing applications. Superpartner configurations are experimentally
      realized in coupled optical networks, and the corresponding light dynamics in
      such systems are directly observed. We show that supersymmetry can be judiciously
      used to remove the fundamental mode of a multimode optical structure while
      establishing global phase-matching conditions for the remaining set of modes.
      Along these lines, supersymmetry may serve as a promising platform for versatile
      optical components with desirable properties and functionalities. 

PMID- 24739257
TI  - Effects of exercise and diet on weight loss maintenance in overweight and obese
      adults: a systematic review.
AB  - Overweight and obesity are widespread nutritional disorders. Their treatment aims
      at effective weight loss (WL) and weight loss maintenance (WLM). Previous
      systematic reviews show weight regain, after recommended exercise and diet
      combined. However, certain experimental and methodological inconsistencies in the
      original studies and in these reviews left space for a substantial revisit of
      this problem. This study aimed at systematically re-reviewing the effectiveness
      of exercise combined with diet on WLM in overweight and obese adults. Literature
      was searched through Embase and Sport Discus (up to 2008), and PubMed (Medline)
      and ISI Web of science (up to 2012). 14 randomized clinical trials (RCT) were
      retained, their quality was assessed by the Jadad scale, and detailed
      methodological and statistical characteristics were evaluated. Overall
      estimations showed a WL of 11.1 kg (about 13%) after an average of about 4 months
      from baseline, a WLM of 5.8 kg (about 52%) and a weight regain of 5.1 kg after an
      average period of about 21 months. WL was successful but almost half of it (about
      48%) was regained, which agrees with previous findings. The Jadad score showed
      very good to excellent quality for all 14 studies. However, further assessment
      revealed serious weakness such as high average dropout (>20%), not estimating
      experimental power or not using a control group in more than half of the studies,
      possible lack of adherence and variability in demographic traits. Future studies
      may focus on improving these limitations for more accurate results in this
      crucial research field. 

PMID- 24739258
TI  - Traditional and ankle-specific vertical jumps as strength-power indicators for
      maximal sprint acceleration.
AB  - AIM: This study aimed to determine the demand of strength-power capabilities
      represented by traditional and ankle-specific vertical jump modalities - squat
      jump (SJ), counter-movement jump (CMJ), rebound-continuous jump (RJ), rebound
      continuous ankle jump (AJ) - relative to sprint acceleration ability during the
      entire acceleration phase of maximal sprint. METHODS: Nineteen male sprinters
      performed a 60-m maximal sprint and various vertical jumps. Correlation
      coefficients among the vertical jump performances and between those and the 60-m
      sprint time and sprint acceleration at each step were calculated. RESULTS: There
      were significant relationships between the 60-m sprint time and SJ height, CMJ
      height, AJ height, and AJ index. AJ height and index had no correlation with any
      other jump variables. Acceleration was significantly correlated with SJ height
      from the 6th to the 10th steps (r=0.48-0.51) and with CMJ height from the 5th to
      the 11th steps (r=0.46-0.54). Acceleration was also correlated with the AJ index
      from the 14th to the 19th steps (r=0.48-0.54). Acceleration had no correlation
      with the RJ index at any step. CONCLUSION: The results suggest that the AJ allows
      assessment of different reactive strengths compared with traditional jump
      modalities. To accelerate effectively, the explosive strengths of the SJ and CMJ
      are important during the early stage of acceleration (from 6.6+/-0.4 to 17.5+/
      0.8 m), and the reactive strength represented by the AJ is necessary during the
      later stage of acceleration (from 23.4+/-1.0 to 33.7+/-1.4 m). Sprinters and
      coaches should be aware of the different demands of strength-power capability for
      effective acceleration.

PMID- 24739259
TI  - The requirement for the LysR-type regulator PtrA for Pseudomonas chlororaphis
      PA23 biocontrol revealed through proteomic and phenotypic analysis.
AB  - BACKGROUND: Pseudomonas chlororaphis strain PA23 is a biocontrol agent capable of
      suppressing the fungal pathogen Sclerotinia sclerotiorum. This bacterium produces
      the antibiotics phenazine and pyrrolnitrin together with other metabolites
      believed to contribute to biocontrol. A mutant no longer capable of inhibiting
      fungal growth was identified harboring a transposon insertion in a gene encoding
      a LysR-type transcriptional regulator (LTTR), designated ptrA (Pseudomonas
      transcriptional regulator). Isobaric tag for relative and absolute quantitation
      (iTRAQ) based protein analysis was used to reveal changes in protein expression
      patterns in the ptrA mutant compared to the PA23 wild type. RESULTS: Relative
      abundance profiles showed 59 differentially-expressed proteins in the ptrA
      mutant, which could be classified into 16 clusters of orthologous groups (COGs)
      based on their predicted functions. The largest COG category was the unknown
      function group, suggesting that many yet-to-be identified proteins are involved
      in the loss of fungal activity. In the secondary metabolite biosynthesis,
      transport and catabolism COG, seven proteins associated with phenazine
      biosynthesis and chitinase production were downregulated in the mutant.
      Phenotypic assays confirmed the loss of phenazines and chitinase activity.
      Upregulated proteins included a lipoprotein involved in iron transport, a
      flagellin and hook-associated protein and four proteins categorized into the
      translation, ribosome structure and biogenesis COG. Phenotypic analysis revealed
      that the mutant exhibited increased siderophore production and flagellar motility
      and an altered growth profile, supporting the proteomic findings. CONCLUSION:
      PtrA is a novel LTTR that is essential for PA23 fungal antagonism. Differential
      protein expression was observed across 16 COG categories suggesting PtrA is
      functioning as a global transcriptional regulator. Changes in protein expression
      were confirmed by phenotypic assays that showed reduced phenazine and chitinase
      expression, elevated flagellar motility and siderophore production, as well as
      early entrance into log phase growth.

PMID- 24739260
TI  - The muscle mass, omega-3, diet, exercise and lifestyle (MODEL) study - a
      randomised controlled trial for women who have completed breast cancer treatment.
AB  - BACKGROUND: Loss of lean body mass (LBM) is a common occurrence after treatment
      for breast cancer and is related to deleterious metabolic health outcomes [Clin
      Oncol, 22(4):281-288, 2010; Appl Physiol Nutr Metab, 34(5):950-956, 2009]. The
      aim of this research is to determine the effectiveness of long chain omega-3
      fatty acids (LCn-3s) and exercise training alone, or in combination, in
      addressing LBM loss in breast cancer survivors. METHODS/DESIGN: A total of 153
      women who have completed treatment for breast cancer in the last 12 months, with
      a Body Mass Index (BMI) of 20 to 35 kg/m2, will be randomly assigned to one of 3
      groups: 3g/d LCn-3s (N-3), a 12-week nutrition and exercise education program
      plus olive oil (P-LC) or the education program plus LCn-3s (EX+N-3). Participants
      randomised to the education groups will be blinded to treatment, and will receive
      either olive oil placebo (OO+N-3) or LCn-3 provision, while the N-3 group will be
      open label. The education program includes nine 60-75 min sessions over 12 weeks
      that will involve breast cancer specific healthy eating advice, plus a supervised
      exercise session run as a resistance exercise circuit. They will also be advised
      to conduct the resistance training and aerobic training 5 to 7 days per week
      collectively. Outcome measures will be taken at baseline, 12-weeks and 24-weeks.
      The primary outcome is % change in LBM as measured by the air displacement
      plethysmograhy. Secondary outcomes include quality of life (FACT-B + 4) and
      inflammation (C-Reactive protein: CRP). Additional measures taken will be
      erythrocyte fatty acid analysis, fatigue, physical activity, menopausal symptoms,
      dietary intake, joint pain and function indices. DISCUSSION: This research will
      provide the first insight into the efficacy of LCn-3s alone or in combination
      with exercise in breast cancer survivors with regards to LBM and quality of life.
      In addition, this study is designed to improve evidence-based dietetic practice,
      and how specific dietary prescription may link with appropriate exercise
      interventions. TRIALS REGISTRATION: ACTRN12610001005044; and World Health
      Organisation Universal trial number: U1111-1116-8520.

PMID- 24739261
TI  - Made-to-measure malaria vector control strategies: rational design based on
      insecticide properties and coverage of blood resources for mosquitoes.
AB  - Eliminating malaria from highly endemic settings will require unprecedented
      levels of vector control. To suppress mosquito populations, vector control
      products targeting their blood hosts must attain high biological coverage of all
      available sources, rather than merely high demographic coverage of a targeted
      resource subset, such as humans while asleep indoors. Beyond defining biological
      coverage in a measurable way, the proportion of blood meals obtained from humans
      and the proportion of bites upon unprotected humans occurring indoors also
      suggest optimal target product profiles for delivering insecticides to humans or
      livestock. For vectors that feed only occasionally upon humans, preferred animal
      hosts may be optimal targets for mosquito-toxic insecticides, and vapour-phase
      insecticides optimized to maximize repellency, rather than toxicity, may be ideal
      for directly protecting people against indoor and outdoor exposure. However, for
      vectors that primarily feed upon people, repellent vapour-phase insecticides may
      be inferior to toxic ones and may undermine the impact of contact insecticides
      applied to human sleeping spaces, houses or clothing if combined in the same time
      and place. These concepts are also applicable to other mosquito-borne
      anthroponoses so that diverse target species could be simultaneously controlled
      with integrated vector management programmes. Measurements of these two crucial
      mosquito behavioural parameters should now be integrated into programmatically
      funded, longitudinal, national-scale entomological monitoring systems to inform
      selection of available technologies and investment in developing new ones. 

PMID- 24739262
TI  - PKC-mediated potentiation of morphine analgesia by St. John's Wort in rodents and
      humans.
AB  - Our purpose was to combine the use of morphine with clinically available
      inhibitors of protein kinase C (PKC), finally potentiating morphine analgesia in
      humans. Thermal tests were performed in rodents and humans previously
      administered with acute or chronic morphine combined or not with increasing doses
      of the PKC-blocker St. John's Wort (SJW) or its main component hypericin.
      Phosphorylation of the gamma subunit of PKC enzyme was assayed by western
      blotting in the periaqueductal grey matter (PAG) from rodents co-administered
      with morphine and hypericin and was prevented in rodent PAG by SJW or hypericin
      co-administration with morphine, inducing a potentiation of morphine analgesia in
      thermal pain. The score of pain assessment in healthy volunteers were decreased
      by 40% when morphine was co-administered with SJW at a dose largely below those
      used to obtain an antidepressant or analgesic effect in both rodents and humans.
      The SJW/hypericin potentiating effect lasted in time and preserved morphine
      analgesia in tolerant mice. Our findings indicate that, in clinical practice, SJW
      could reduce the dose of morphine obtaining the same analgesic effect. Therefore,
      SJW and one of its main components, hypericin, appear ideal to potentiate
      morphine-induced analgesia. 

PMID- 24739263
TI  - Increased levels of fatty acids contributed to induction of hepatic CYP3A4
      activity induced by diabetes - in vitro evidence from HepG2 cell and Fa2N-4 cell
      lines.
AB  - Accumulating evidences have shown that diabetes upregulated the function and
      expression of CYP3A4, but the mechanism remained unclear. In this study, HepG2
      cells were incubated with serum from diabetic rats induced by streptozotocin, and
      the activity of CYP3A4 was measured by substrate metabolism. Results showed that
      incubation with diabetic serum significantly induced CYP3A4 activity in HepG2
      cells. To identify the specific factors contributing to the regulation, the
      abnormally altered components in diabetic serum, including glucose, insulin,
      cholesterol, and free fatty acids were screened. It was found that only fatty
      acids concentration-dependently up-regulated CYP3A4 activity, and the induction
      by fatty acids was further confirmed in Fa2N-4 cells. Data from western blotting
      and QT-PCR showed that induction of CYP3A4 activity was associated with up
      regulation of CYP3A4 protein and mRNA levels. In addition, effects of
      pharmacological inhibitors on fatty acid-induced CYP3A4 activity were studied.
      The results indicated that the induction of CYP3A4 activity by oleic acid may be
      partly via AMPK-, PKC-, and NF-kappaB-dependent pathways, whereas that by
      palmitic acid was possibly associated with the PKC-dependent pathway. In
      conclusion, the increased levels of fatty acids may be one of the reasons leading
      to the elevated function and expression of CYP3A4 under diabetic conditions. 

PMID- 24739264
TI  - Aggravation of clozapine-induced hepatotoxicity by glycyrrhetinic acid in rats.
AB  - Clozapine (CLZ) was reported to be associated with hepatotoxicity. Glycyrrhetinic
      acid (GA) has a liver protective effect. Our preliminary experiments showed that
      GA aggravated rather than attenuated CLZ-induced hepatotoxicity in primary
      cultured rat hepatocytes. The study aimed to describe the enhancing effect of GA
      on CLZ-induced hepatotoxicity in vivo and in vitro. Data from primary cultured
      rat hepatocytes showed the decreased formation of metabolites demethylclozapine
      (nor-CLZ) and clozapine N-oxide (CLZ N-oxide). The results in vivo showed that 7
      day CLZ treatment led to marked accumulation of triglyceride (TG) and increase in
      gamma-glutamyl transpeptidase (gamma-GT) activity, liver weight, and serum AST in
      rats. Co-administration of GA enhanced the increases in hepatic TG, gamma-GT,
      liver weight, and serum total cholesterol induced by CLZ. GA decreased plasma
      concentrations of nor-CLZ and CLZ N-oxide. Compared with control rats, hepatic
      microsomes of GA rats exhibited the decreased formations of nor-CLZ and CLZ N
      oxide, accompanied by decreases in activities of CYP2C11 and CYP2C19 and
      increased activity of CYP1A2. QT-PCR analysis demonstrated that GA enhanced
      expression of CYP1A2, but suppressed expression of CYP2C11 and CYP2C13. All these
      results support the conclusion that GA aggravated CLZ-induced hepatotoxicity,
      which was partly via inhibiting CYP2C11 and CYP2C13 or inducing CYP1A2.

PMID- 24739265
TI  - CRM1 is a direct cellular target of the natural anti-cancer agent plumbagin.
AB  - Plumbagin, a naphthoquinone derived from the medicinal plant Plumbago zeylanica,
      has been shown to exert anti-cancer and anti-proliferative activities in vitro as
      well as in animal tumor models. However, the mechanism underlying its anti-tumor
      action still remains unclear. CRM1 is a nuclear export receptor involved in the
      active transport of tumor suppressors whose function is altered in cancer due to
      increased expression and overactive transport. We showed that CRM1 is a direct
      cellular target of plumbagin. The nuclei of cells incubated with plumbagin
      accumulated tumor-suppressor proteins and inhibited the interactions between CRM1
      and these proteins. Particularly, we demonstrated that plumbagin could
      specifically react with the conserved Cys(528) of CRM1 but not with a Cys(528)
      mutant peptide through Mass spectrometric analysis. More importantly, cancer
      cells that are transfected with mutant CRM1 (C528S) are resistant to the
      inhibitory effects of plumbagin, demonstrating that the inhibition is through
      direct interaction with Cys(528) of CRM1. The inhibition of nuclear traffic by
      plumbagin may account for its therapeutic properties in cancer and inflammatory
      diseases. Our findings could contribute to the development of a new class of CRM1
      inhibitors. 

PMID- 24739266
TI  - Obesity--a risk factor for asthma, but not for atopic dermatitis, allergic
      rhinitis and sensitization.
AB  - OBJECTIVE: To analyse the relationship between obesity and overweight and the
      prevalence of allergic diseases and sensitization, and the impact of gender and
      place of residence. DESIGN: Questionnaire based on those used in ISAAC
      (International Study of Asthma and Allergies in Childhood) and ECRHS (European
      Community Respiratory Health Survey). SETTING: Our study involved populations of
      the eight largest cities and one rural region in Poland (each with over 150,000
      inhabitants). SUBJECTS: The study included 18,617 participants (24.2% aged 6-7
      years, 25.4% aged 13-14 years, 50.4% adults aged 20-44 years) in eight cities and
      one rural area. The out-patient study involved 4783 patients (25.7%); we
      performed skin prick testing with fifteen aeroallergens. RESULTS: Overweight was
      found in 16.13% of participants (9.11% of 6-7-year-olds, 4.90% of 13-14-year-olds
      and 25.61% of adults), obesity in 6.41% (7.16%, 2.45% and 8.36%, respectively).
      In adults, overweight (OR=1.34) and obesity (OR=1.80) increased the prevalence of
      asthma, especially in women (OR=1.53, OR=2.01). Among 13-14-year-olds the
      prevalence was higher only in the obese (OR=1.76). Overweight (OR=1.99) and
      obesity (OR=2.17) affected the incidence of doctor-diagnosed asthma in 6-7-year
      olds. Overweight (OR=0.81) and obesity (OR=0.76) reduced the prevalence of
      allergic rhinitis in men. There was no relationship between BMI and asthma in
      people from rural areas. Obesity and overweight did not affect the frequency of
      sensitization to aeroallergens. CONCLUSIONS: Overweight and obesity increased the
      prevalence of symptomatic asthma in adults, especially in women. In 13-14-year
      olds, only obesity increased the prevalence of asthma. In children, overweight
      was associated with increased prevalence of clinically diagnosed and declared
      asthma and a trend towards atopy. Higher BMI was negatively associated with the
      prevalence of allergic rhinitis in overweight and obese man. There was no
      correlation between BMI and sensitization to aeroallergens.

PMID- 24739267
TI  - Towards cardiopulmonary resuscitation without vasoactive drugs.
AB  - PURPOSE OF REVIEW: Whereas there is clear evidence for improved survival with
      cardiopulmonary resuscitation (CPR) and defibrillation during cardiac arrest
      management, there is today lacking evidence that any of the recommended and used
      drugs lead to any long-term benefit for the patients. In this review, we try to
      discuss our current view on why advanced life support (ALS) today can be
      performed without the use of drugs, and instead gain all focus on improving the
      tasks we know improve survival: CPR and defibrillation. RECENT FINDINGS: Previous
      and recent cardiac arrest drug studies have been reviewed. These are mostly
      consisting of retrospective register data, some experimental data and a few new
      randomized trials. The alternative drug-free ALS concept is also discussed with
      relevant studies. SUMMARY: There is currently no evidence to support any specific
      drugs during cardiac arrest. Good-quality CPR, early defibrillation and goal
      directed postresuscitation care is more important. Healthcare systems should not
      prioritize implementation of unproven drugs before good quality of care can be
      documented. More drug studies are indeed required, and future research needs to
      incorporate better diagnostic tools to test more specific and tailored therapies
      that account for underlying causes and individual responsiveness.

PMID- 24739268
TI  - Electrical impedance tomography imaging of the cardiopulmonary system.
AB  - PURPOSE OF REVIEW: This review article summarizes the recent advances in
      electrical impedance tomography (EIT) related to cardiopulmonary imaging and
      monitoring on the background of the 30-year development of this technology.
      RECENT FINDINGS: EIT is expected to become a bedside tool for monitoring and
      guiding ventilator therapy. In this context, several studies applied EIT to
      determine spatial ventilation distribution during different ventilation modes and
      settings. EIT was increasingly combined with other signals, such as airway
      pressure, enabling the assessment of regional respiratory system mechanics. EIT
      was for the first time used prospectively to define ventilator settings in an
      experimental and a clinical study. Increased neonatal and paediatric use of EIT
      was noted. Only few studies focused on cardiac function and lung perfusion.
      Advanced radiological imaging techniques were applied to assess EIT performance
      in detecting regional lung ventilation. New approaches to improve the quality of
      thoracic EIT images were proposed. SUMMARY: EIT is not routinely used in a
      clinical setting, but the interest in EIT is evident. The major task for EIT
      research is to provide the clinicians with guidelines how to conduct, analyse and
      interpret EIT examinations and combine them with other medical techniques so as
      to meaningfully impact the clinical decision-making.

PMID- 24739269
TI  - Functional residual capacity and absolute lung volume.
AB  - PURPOSE OF REVIEW: To discuss the role of measuring functional residual capacity
      (FRC) during mechanical ventilation to improve patient ventilator settings in
      order to prevent ventilator-induced lung injury. RECENT FINDINGS: Nowadays, FRC
      can be measured without the use of tracer gases and without disconnection from
      the ventilator. It is shown that FRC can provide additional information to
      optimize the ventilator setting; for example, FRC measurements can differentiate
      between responders and nonresponders after a recruitment maneuver, and in
      combination with dynamic compliance one can differentiate between recruitment and
      overdistention during a positive end-expiratory pressure trial. In addition, FRC
      measurements enable not only to estimate stress and strain at the bedside, but
      also to estimate ventilation inhomogeneity. SUMMARY: In conclusion, measuring FRC
      could be extremely valuable during mechanical ventilation, but clinical studies
      are needed to prove whether this technique will improve outcome.

PMID- 24739270
TI  - Vigorous exercise in clinical practice: balancing risks and benefits.

PMID- 24739271
TI  - Response.

PMID- 24739272
TI  - Experimental studies on the effect of (Lambda-Cyhalothrin) insecticide on lungs
      and the ameliorating effect of plant extracts (Ginseng (Panax Ginseng) and garlic
      (Allium sativum L.) on asthma development in albino rats.
AB  - BACKGROUND: Lambda-cyhalothrin (LTC) is a synthetic pyrethroid insecticide for
      agricultural and public health applications. This study was to determine the
      pathological alterations of LTC in lungs, which has not previously been studied,
      and the ameliorating effects of plant extracts (ginseng and garlic) on the
      development of asthma in albino rats. METHODS: Four groups (gps) of albino rats,
      (n = 20, average body weight = 200 gm with an age of 4 months), were formed. Gp 1
      was kept as control. Gp 2 was injected intraperitoneally (i.p.) with LTC at a
      dose of 1/6 LD50 that is 9.34 mg/kg body weight (w.t.) daily for 21 days (d). Gp
      3 & 4 were injected (i.p.) with ginseng at the dose of 200 mg/kg b.wt and garlic
      (Allium sativum L.) at the dose of 100 mg/kg b.wt., respectively, one hour before
      being given LTC at a dose of 1/6 LD50 (9.34 mg/kg b.wt.) daily. Each groups were
      divided into two sacrificed, at 15 and 21 d p.i. Blood and lung samples were
      collected for hematological and histopathological examinations. RESULTS:
      Hematological findings showed that the animals in gps 2 and 3, which were treated
      for 21 days, showed a significant difference in RBC counts (P > .001), Hb (P >
      .007), PCV% (P > .004), (P > .008) in comparison with the control group. Signs of
      cough and nasal discharge were seen in gp 2, which became mild in gp 4. Grossly,
      the lungs showed congestion and consolidation in gp 2. Histopathologically,
      macroabscesses and interstitial alveolitis were seen in gp 2, which led to
      obstruction in the lumen of the bronchioles at 21 d p.i. Meanwhile, thickening in
      the interalveolar septa with mononuclear cells was seen in gps. 3 and 4 at 21d
      p.i. CONCLUSIONS: The study shows 3 gps of rats injected with LHC alone or
      combined with garlic and ginseng extract, each group were divided into two
      sacrificed (15 and 21 d p.i.). Lambda cyhalothrin causes bronchial obstruction in
      the lungs of the rats (15 and 21 d p.i), which decreased into mild to moderate
      interstitial inflammation in the rats given garlic and ginseng, respectively.

PMID- 24739273
TI  - Modulation of the host microenvironment by a common non-oncolytic mouse virus
      leads to inhibition of plasmacytoma development through NK cell activation.
AB  - Although many cells undergo transformation, few actually develop into tumours,
      due to successful mechanisms of immunosurveillance. To investigate whether an
      infectious agent may play a role in this process, the growth of a plasmacytoma
      was investigated in mice infected by lactate dehydrogenase-elevating virus.
      Acutely infected animals were significantly protected against tumour development.
      The mechanisms responsible for this protection were analysed in mice deficient
      for relevant immune cells or molecules and after in vivo cell depletion. This
      protection by viral infection correlated with NK cell activation and with IFN
      gamma production. It might also be related to activation of NK/T-cells, although
      this remains to be proven formally. Therefore, our results indicated that
      infections with benign micro-organisms may protect the host against cancer
      development, through non-specific stimulation of the host's innate immune system
      and especially of NK cells. 

PMID- 24739274
TI  - Liquid chromatography-tandem mass spectrometry method for determination of
      aliskiren in saliva and its application to a clinical trial with healthy
      volunteers.
AB  - Although serum and plasma are the biological fluids of choice for pharmacokinetic
      determination of drugs in adults, it is desirable to elucidate noninvasive
      methods which can be used for investigations in vulnerable groups such as
      children. If the drug properties grant sufficient penetration of the drug from
      blood into saliva, the latter is a useful matrix for noninvasive investigations.
      Concerning the known physicochemical properties, the direct renin inhibitor
      aliskiren is one of the substances of which saliva concentrations could
      substitute blood concentrations for pharmacokinetic investigations in children.
      Therefore, a reliable bioanalytical method was successfully developed and
      validated according to the criteria of current international bioanalytical
      guidelines to enable the comparison of blood and saliva concentrations of
      aliskiren. After purification of the fluid by solid-phase extraction the
      chromatographic separation was conducted by using XselectTM C18 CSH columns.
      Applying a mobile phase gradient of acidified methanol and acidified water at a
      flow rate of 0.4ml/min the column effluent was monitored during a total run time
      of 7.5min by tandem mass spectrometry with electrospray ionization. Running in
      positive mode the following transitions were investigated: 552.2-436.2m/z for
      aliskiren and 425.3-351.2m/z for benazepril (internal standard). Calibration
      curves were constructed in the range of 0.586-1200ng/ml and were analyzed
      utilizing 1/x(2) weighted linear regression. Intra-run and inter-run precision
      were 3.8-8.1% and 3.4-8.9%. The method provides selectivity, linearity and
      accuracy. The validated method was then applied to determine aliskiren
      concentrations in saliva and blood of three healthy volunteers after oral
      administration of 300mg aliskiren. 

PMID- 24739275
TI  - Discharges from an early intervention in psychosis service: where do patients
      stand after 3 years?
AB  - AIM: Continuity of care is an important therapeutic factor in psychiatric
      services. This study aimed to look at the continuity of care for patients
      following discharge from an early intervention in psychosis service. METHOD:
      Continuity of care was assessed by looking at whether a patient was still with
      the same service after 3 years or more following discharge from an early
      intervention in psychosis service. If not, records were checked to see where
      their care had moved. Discharges from 2006 to 2009 were included in the study.
      RESULTS: Descriptive statistics were worked out to calculate the proportion of
      service users who remained with the same service and those who had moved to other
      services. About 8% of patients had moved to another service during the identified
      study period. Only 4% of patients had moved from a less intensive to a more
      intensive service within this time. CONCLUSIONS: The findings from this study
      showed that only a very small proportion of patients discharged from an early
      intervention in psychosis service move to another service in the 3 years
      following their discharge. Movement of patients to a more intensive service after
      discharge from the early intervention in psychosis team was even lower. Most
      patients thereby have a stable continuity of care following discharge from an
      early intervention team.

PMID- 24739276
TI  - Mechanical offloading of incisional wounds is associated with transcriptional
      downregulation of inflammatory pathways in a large animal model.
AB  - Cutaneous scarring is a major source of morbidity and current therapies to
      mitigate scar formation remain ineffective. Although wound fibrosis and
      inflammation are highly linked, only recently have mechanical forces been
      implicated in these pathways. Our group has developed a topical polymer device
      that significantly reduces post-injury scar formation via the manipulation of
      mechanical forces. Here we extend these studies to examine the genomewide
      transcriptional effects of mechanomodulation during scar formation using a
      validated large animal model, the red Duroc pig. We demonstrate that mechanical
      loading of incisional wounds upregulates expression of genes associated with
      inflammatory and fibrotic pathways, and that device-mediated offloading of these
      wounds reverses these effects. Validation studies are needed to clarify the
      clinical significance of these findings.

PMID- 24739277
TI  - Inherited Thrombophilia.
AB  - Thrombophilia alters normal hemostasis, shifting the balance in favor of thrombus
      formation. Inherited conditions include factor V Leiden (FVL), prothrombin
      G20210A mutation, deficiencies in natural anticoagulants (antithrombin [AT],
      protein C, and protein S), hyperhomocysteinemia, and elevations in clotting
      factors (factors VIII and XI). Although FVL and prothrombin mutation are common
      disorders, deficiencies in the natural anticoagulants are rare. The risk of
      initial thrombosis conferred by inherited thrombophilia varies with the highest
      risk in those homozygous for either FVL or prothrombin mutation, or with AT
      deficiency. In the nonpregnant patient, the presence of a thrombophilia does not
      affect treatment of an acute event. Although vitamin B supplementation has been
      shown to decrease the levels of homocysteine, the treatment has failed to show a
      benefit in thrombus prevention and is therefore not recommended. 

PMID- 24739278
TI  - Thrombophilia Issue.

PMID- 24739279
TI  - Thrombophilia Screening.
AB  - Although controversial, screening for thrombophilia has become common. Testing
      for antiphospholipid antibodies is indicated in order to guide treatment
      decisions if there is clinical suspicion for antiphospholipid syndrome. The
      utility of identifying other thrombophilias in symptomatic venous thromboembolism
      (VTE) is questionable, as the risk of recurrence does not appear to be increased
      by an appreciable degree with the most common disorders (heterozygosity for
      factor V Leiden or prothrombin mutation). Although recurrence appears to be
      increased in those with homozygous or multiple abnormalities and potentially
      deficiencies in natural anticoagulants, screening to detect these conditions is
      difficult to justify based on their rarity. The American College of Chest
      Physicians' current guidelines note the increased risk of recurrence with
      idiopathic, proximal events regardless of thrombophilia status. They suggest
      duration of anticoagulation therapy be based on location and provoking factors
      rather than whether or not the individual has a thrombophilia. Because routine
      prophylaxis in asymptomatic individuals with thrombophilia is not recommended,
      screening of asymptomatic family members is difficult to justify. Screening prior
      to prescribing combination oral contraceptives is not cost effective, may result
      in unwanted pregnancies, and may have little effect on the overall rate of VTE. 

PMID- 24739280
TI  - Shared developmental programme strongly constrains beak shape diversity in
      songbirds.
AB  - The striking diversity of bird beak shapes is an outcome of natural selection,
      yet the relative importance of the limitations imposed by the process of beak
      development on generating such variation is unclear. Untangling these factors
      requires mapping developmental mechanisms over a phylogeny far exceeding model
      systems studied thus far. We address this issue with a comparative morphometric
      analysis of beak shape in a diverse group of songbirds. Here we show that the
      dynamics of the proliferative growth zone must follow restrictive rules to
      explain the observed variation, with beak diversity constrained to a three
      parameter family of shapes, parameterized by length, depth and the degree of
      shear. We experimentally verify these predictions by analysing cell proliferation
      in the developing embryonic beaks of the zebra finch. Our findings indicate that
      beak shape variability in many songbirds is strongly constrained by shared
      properties of the developmental programme controlling the growth zone. 

PMID- 24739281
TI  - Total glucosides of paeony attenuate renal tubulointerstitial injury in STZ
      induced diabetic rats: role of Toll-like receptor 2.
AB  - Accumulating evidence suggested that macrophages induce tubulointerstitial
      injury. Total glucosides of paeony (TGP), extracted from Paeonia lactiflora, has
      presented anti-inflammatory activities in diabetic kidney disease. This research
      will investigate the protective effect of TGP on renal tubulointerstitium and its
      mechanism in streptozotocin-induced diabetic rats. TGP was administered orally at
      a dose of 50, 100, and 200 mg.kg(-1).d(-1) for 8 weeks. Tubulointerstitial injury
      was quantified, followed by immunohistochemistry analysis of renal alpha-smooth
      muscle actin (alpha-SMA), E-cadherin (E-cad) expression, nuclear factor kappa B
      (NF-kappaB)-p-p-65(+), Toll-like receptor (TLR)2(+), and ED-1(+) cell
      infiltration in renal tubulointerstitium. Renal TLR2(+) macrophages were detected
      by double immunohistochemical staining. Western blotting was used to detect the
      TLR2 expression. Histologically, there was marked accumulation of TLR2(+), NF
      kappaB-p-p-65(+), ED-1(+) cells, and ED-1(+)TLR2(+) cells (macrophages) in the
      diabetic kidney and TGP treatment could alleviate it. Accompanying with that, the
      tubulointerstitial injury was ameliorated, alpha-SMA expression was lower, and E
      cad expression was higher compared with the diabetic rats. Western blot analysis
      showed that the expression of TLR2 protein was significantly increased in the
      kidney of the diabetic rats, whereas TGP treatment reduced it. Our study showed
      that TGP could prevent renal tubulointerstitium injury in diabetic rats through a
      mechanism that may be at least partly correlated with suppression of increased
      macrophage infiltration and the expression of TLR2.

PMID- 24739283
TI  - Future prospects for regenerated heart using induced pluripotent stem cells.
AB  - Induced pluripotent stem cell (iPSC) generation is an epoch-making technology.
      The potential applications for iPSCs are wide-ranging from in vitro disease
      models to drug discovery. For regenerative medicine in particular, the technology
      provides great hope for patients with incurable diseases or potentially fatal
      disorders such as heart failure (HF). However, the true realization of that
      promise for HF remains uncertain and moving toward the clinical application of
      iPSCs needs to be stepwise and careful. The establishment of "safe" iPSCs must be
      a major premise, while genome integration-free and oncogene-free reprogramming is
      also necessary. Teratoma formation also remains a risk with undifferentiated
      iPSCs, but it must not happen in patients' bodies. Thus, regardless of the target
      organ, the differentiated cells from iPSCs must be purified to exclude any
      possibility of tumorigenicity. The transplantation strategies used for iPSC
      derived cells are very important for the recovery of lost cardiac function.
      Longer engraftment of transplanted iPSCs-derived cardiomyocytes is essential
      particularly because their survival could be hampered by ischemia, inflammation,
      apoptosis, immunological rejection, and other cardiac phenomena. Providing these
      multistep solutions will open the new frontier of regenerative therapies with
      iPSCs for patients with severe HF.

PMID- 24739282
TI  - Procaterol but not dexamethasone protects 16HBE cells from H2O2-induced oxidative
      stress.
AB  - Oxidative stress is an important pathophysiological factor of asthma and chronic
      obstructive pulmonary disease (COPD). We hypothesized that procaterol and
      dexamethasone might treat inflammation through inhibiting oxidative stress in
      vitro. This study evaluated procaterol and dexamethasone in the hydrogen peroxide
      (H2O2)-induced immortal human bronchial epithelial cell model of oxidative stress
      and investigated the underlying mechanisms. Results showed that exposure to 125
      MUM H2O2 for 2 h led to a 50% reduction in the cell viability, significantly
      increased the percentage of apoptosis, and elevated levels of malondialdehyde and
      reactive oxygen species. Pretreatment with procaterol (25 - 200 nM) could reduce
      these effects in a dose-dependent manner. In contrast, pretreatment with
      dexamethasone (100 nM, 1000 nM) was inefficient. Pretreatment with procaterol
      plus dexamethasone (100 nM procaterol + 1000 nM dexamethasone) was effective, but
      the combined effect was not more effective than the sole pretreatment with 100 nM
      procaterol. The nuclear factor kappa-B (NF-kappaB) pathway was involved in the
      pathogenic mechanisms of H2O2. Procaterol may indirectly inhibit H2O2-induced
      activation of the NF-kappaB pathway due to its capability of antioxidation.
      Glucocorticoids may be not recommended to treat asthma or COPD complicated with
      severe oxidative stress.

PMID- 24739284
TI  - Common sequence variants in the LOXL1 gene in pigment dispersion syndrome and
      pigmentary glaucoma.
AB  - BACKGROUND: Single nucleotide polymorphisms (SNPs) within the LOXL1 gene are
      associated with pseudoesfoliation syndrome and pseudoesfoliation glaucoma. The
      aim of our study is to investigate a potential involvement of LOXL1 gene in the
      pathogenesis of pigment dispersion syndrome (PDS) and pigmentary glaucoma (PG).
      METHODS: A cohort of Caucasian origin of 84 unrelated and clinically well
      characterised patients with PDS/PG and 200 control subjects were included in the
      study. Genomic DNA from whole blood was extracted and the coding and regulatory
      regions of LOXL1 gene were risequenced in both patients and controls to identify
      unknown sequence variations. Genotype and haplotype analysis were performed with
      UNPHASED software. The expression levels of LOXL1 were determined on c-DNA from
      peripheral blood lymphocytes by quantitative real-time RT-PCR. RESULTS: A
      significant allele association was detected for SNP rs2304722 within the fifth
      intron of LOXL1 (Odds ratio (OR = 2.43, p-value = 3,05e-2). Haplotype analysis
      revealed the existence of risk and protective haplotypes associated with PG-PDS
      (OR = 3.35; p-value = 1.00e-5 and OR = 3.35; p-value = 1.00e-4, respectively).
      Expression analysis suggests that associated haplotypes can regulate the
      expression level LOXL1. CONCLUSIONS: Haplotypes of LOXL1 are associated with PG
      PDS independently from rs1048661, leading to a differential expression of the
      transcript.

PMID- 24739285
TI  - Hyperimmune intravenous immunoglobulin containing high titers of pandemic H1N1
      hemagglutinin and neuraminidase antibodies provides dose-dependent protection
      against lethal virus challenge in SCID mice.
AB  - BACKGROUND: Convalescent plasma and fractionated immunoglobulins have been
      suggested as prophylactic or therapeutic interventions during an influenza
      pandemic. FINDINGS: Intravenous immunoglobulin (IVIG) preparations manufactured
      from human plasma collected before the 2009 H1N1 influenza pandemic, and post
      pandemic hyperimmune (H)-IVIG preparations were characterized with respect to
      hemagglutination inhibition (HI), microneutralization (MN) and neuraminidase
      inhibiting (NAi) antibody titers against pandemic H1N1 (pH1N1) and seasonal H1N1
      (sH1N1) viruses. The protective efficacy of the IVIG and H-IVIG preparations was
      evaluated in a SCID mouse challenge model.Substantial levels of HI, MN and NAi
      antibodies against pH1N1 (GMTs 1:45, 1:204 and 1: 727, respectively) and sH1N1
      (GMTs 1:688, 1:4,946 and 1:312, respectively) were present in pre-pandemic IVIG
      preparations. In post-pandemic H-IVIG preparations, HI, MN and NAi antibody GMTs
      against pH1N1 were 1:1,280, 1:11,404 and 1:2,488 (28-, 56- and 3.4-fold
      enriched), respectively, compared to pre-pandemic IVIG preparations (p < 0.001).
      Post-pandemic H-IVIG (HI titer 1:1,280) provided complete protection from
      lethality of SCID mice against pH1N1 challenge (100% of mice survived for 29 days
      post-challenge). Pre-pandemic IVIG (HI titer 1:70) did not provide significant
      protection against pH1N1 challenge (50% of mice survived 29 days post-challenge
      compared to 40% survival in the buffer control group). There was a highly
      significant correlation between circulating in vivo HI and MN antibody titers and
      survival (p < 0001). CONCLUSION: The substantial enrichment of HA- and NA
      specific antibodies in H-IVIG and the efficacious protection of SCID mice against
      challenge with pH1N1 suggests H-IVIG as a promising intervention against pandemic
      influenza for immunocompromised patients and other risk groups.

PMID- 24739286
TI  - Limitations of haemozoin-based diagnosis of Plasmodium falciparum using dark
      field microscopy.
AB  - BACKGROUND: The haemozoin crystal continues to be investigated extensively for
      its potential as a biomarker for malaria diagnostics. In order for haemozoin to
      be a valuable biomarker, it must be present in detectable quantities in the
      peripheral blood and distinguishable from false positives. Here, dark-field
      microscopy coupled with sophisticated image processing algorithms is used to
      characterize the abundance of detectable haemozoin within infected erythrocytes
      from field samples in order to determine the window of detection in peripheral
      blood. METHODS: Thin smears from Plasmodium falciparum-infected and uninfected
      patients were imaged in both dark field (DF) unstained and bright field (BF)
      Giemsa-stained modes. The images were co-registered such that each parasite had
      thumbnails in both BF and DF modes, providing an accurate map between parasites
      and DF objects. This map was used to find the abundance of haemozoin as a
      function of parasite stage through careful parasite staging and correlation with
      DF objects. An automated image-processing and classification algorithm classified
      the bright spots in the DF images as either haemozoin or non-haemozoin objects.
      RESULTS: The algorithm distinguishes haemozoin from non-haemozoin objects in DF
      images with an object-level sensitivity of 95% and specificity of 97%. Ring
      stages older than about 6 hours begin to show detectable haemozoin, and rings
      between 10-16 hours reliably contain detectable haemozoin. However, DF microscopy
      coupled with the image-processing algorithm detect no haemozoin in rings younger
      than six hours. DISCUSSION: Although this method demonstrates the most sensitive
      detection of haemozoin in field samples reported to date, it does not detect
      haemozoin in ring-stage parasites younger than six hours. Thus, haemozoin is a
      poor biomarker for field samples primarily composed of young ring-stage parasites
      because the crystal is not present in detectable quantities by the methods
      described here. Based on these results, the implications for patient-level
      diagnosis and recommendations for future work are discussed.

PMID- 24739287
TI  - Effects of exercise mode and participant sex on measures of anaerobic capacity.
AB  - AIM: The purpose of this study was to compare values of maximal accumulated
      oxygen deficit (MAOD; a measure of anaerobic capacity) and peak post-exercise
      blood lactate concentration ([lactate]; a reflection of glycolytic contribution)
      in running and cycling, in women and men. METHODS: One hundred and nineteen women
      and 104 men performed an exhaustive treadmill test of ~5 min duration; 106 women
      and 110 men performed an exhaustive cycle ergometer test of ~5 min duration.
      Oxygen demands for the exhaustive exercise tests were estimated by extrapolation
      from steady state VO2 values. For running, an upwardly curvilinear relationship
      between demand and speed (i.e., with demand a function of speed1.05) was used.
      For cycling, a linear relationship between demand and work rate was used.
      RESULTS: The MAOD was 22% higher (P<0.01) in running than in cycling, and 32%
      higher (P<0.01) in men than in women. Peak [lactate] was 8% higher (P<0.01) in
      running, and 23% higher (P<0.01) in men. The VO2max was 10% higher (P<0.01) in
      running, and 14% higher (P<0.01) in men. CONCLUSION: These results indicate that
      some of the differences between running and cycling, which affect MAOD, do not
      similarly affect VO2max or peak [lactate]. It is possible that greater lactate
      removal by the upper body musculature during running permits the greater
      anaerobic capacity in running, and explains the relatively small difference in
      blood [lactate] in running compared to cycling.

PMID- 24739288
TI  - Heart rate recovery in elite Spanish male athletes.
AB  - AIM: During postexercise recovery, heart rate (HR) initially falls rapidly,
      followed by a period of slower decrease, until resting values are reached. The
      aim of the present work was to examine the differences in the recovery heart rate
      (RHR) between athletes engaged in static and dynamic sports. METHODS: The study
      subjects were 294 federated sportsmen competing at the national and international
      level in sports classified using the criteria of Mitchell et al. as either
      prevalently static (N.=89) or prevalently dynamic (N.=205). Within the dynamic
      group, the subjects who practised the most dynamic sports were assigned to
      further subgroups: triathlon (N.=20), long distance running (N.=58), cycling
      (N.=28) and swimming (N.=12). All athletes were subjected to a maximum exertion
      stress test and their HR recorded at 1, 2, 3 and 4 min (RHR1,2,3,4) into the HR
      recovery period. The following indices of recovery (IR) were then calculated:
      IR1=(HRpeak-RHR1,2,3,4)/(HRmax-HRrest)*100, IR2=(HRpeak
      RHR1,2,3,4)/(HRmax/HRpeak), and IR3=HRpeak-RHR1,2,3,4. The differences in the RHR
      and IR for the static and dynamic groups were examined using two way ANOVA.
      RESULTS: The RHR at minutes 2 (138.7+/-15.2 vs. 134.8+/-14.4 beats.min-1) and 3
      (128.5+/-15.2 vs. 123.3+/-14.4 beats.min-1) were significantly higher for the
      static group (Group S) than the dynamic group (Group D), respectively.
      Significant differences were seen between Group D and S with respect to IR1 at
      minutes 1 (26.4+/-8.7 vs. 24.8+/-8.4%), 2 (43.8+/-8.1 vs. 41.5+/-7.8%), 3 (52.1+/
      8.3 vs. 49.1+/-8%) and 4 (56.8+/-8.6 vs. 55.4+/-7.4%) of recovery. For IR2,
      significant differences were seen between the same groups at minutes 2 (59.7+/
      12.5 vs. 55.9+/-10.8 beats.min-1) and 3 (71.0+/-13.5 vs. 66.1+/-11.4 beats.min-1)
      of recovery. Finally, for IR3, the only significant difference between Group D
      and S was recorded at minute 3 of recovery (72.2+/-12.5 vs. 66.2+/-11.5 beats.min
      1). CONCLUSION: This work provides information on RHR of a large population of
      elite Spanish athletes, and shows marked differences in the way that HR recovers
      in dynamic and static sports.

PMID- 24739289
TI  - Blood lactate clearance after maximal exercise depends on active recovery
      intensity.
AB  - AIM: High-intensity exercise is time-limited by onset of fatigue, marked by
      accumulation of blood lactate. This is accentuated at maximal, all-out exercise
      that rapidly accumulates high blood lactate. The optimal active recovery
      intensity for clearing lactate after such maximal, all-out exercise remains
      unknown. Thus, we studied the intensity-dependence of lactate clearance during
      active recovery after maximal exercise. METHODS: We constructed a standardized
      maximal, all-out treadmill exercise protocol that predictably lead to voluntary
      exhaustion and blood lactate concentration>10 mM. Next, subjects ran series of
      all-out bouts that increased blood lactate concentration to 11.5+/-0.2 mM,
      followed by recovery exercises ranging 0% (passive)-100% of the lactate
      threshold. RESULTS: Repeated measurements showed faster lactate clearance during
      active versus passive recovery (P<0.01), and that active recovery at 60-100% of
      lactate threshold was more efficient for lactate clearance than lower intensity
      recovery (P<0.05). Active recovery at 80% of lactate threshold had the highest
      rate of and shortest time constant for lactate clearance (P<0.05), whereas the
      response during the other intensities was graded (100%=60%>40%>passive recovery,
      P<0.05). CONCLUSION: Active recovery after maximal all-out exercise clears
      accumulated blood lactate faster than passive recovery in an intensity-dependent
      manner, with maximum clearance occurring at active recovery of 80% of lactate
      threshold.

PMID- 24739290
TI  - Greater volumes of static and dynamic stretching within a warm-up do not impair
      star excursion balance performance.
AB  - Based on the conflicting static stretching (SS) literature and lack of dynamic
      stretching (DS) literature regarding the effects of differing volumes of
      stretching on balance, the present study investigated the effects of 4, 8, and 12
      sets of SS and DS following a 5 min aerobic running warm-up on the star excursion
      balance test (SEBT). The objective was to examine an optimal stretch modality and
      volume to enhance dynamic balance. A randomized, within-subjects experimental
      design with repeated measures for stretching (SS and DS) versus no-stretching
      treatment was used to examine the acute effects of 10 (4 sets), 20 (8 sets), and
      30 (12 sets) min, of 15s repetitions per muscle of SS and/or DS following a 5 min
      aerobic warm-up on the performance of the SEBT. Results indicated that a warm-up
      employing either SS or DS of any volume generally improves SEBT by a "small"
      amount with effect sizes ranging from 0.06 to 0.50 (11 of 18 conditions>75%
      likely to exceed the 1.3-1.9% smallest worthwhile change). Secondly, the
      difference between static and dynamic warm-up on this observed improvement with
      warm-up improvement was "trivial" to "moderate" (d=0.04 to 0.57) and generally
      "unclear" (only two of nine conditions>75% likely to exceed the smallest
      worthwhile change). Finally, the effect of increasing the volume of warm-up on
      the observed improvement with a warm-up is "trivial" to "small" (d<0.40) and
      generally "unclear" (only three of 12 conditions>75% likely to exceed the
      smallest worthwhile change). In summary, an aerobic running warm-up with
      stretching that increases core and muscle temperature whether it involves SS or
      DS may be expected to provide small improvements in the SEBT.

PMID- 24739291
TI  - Acute partial passive stretching increases range of motion and muscle strength.
AB  - AIM: The purpose of this study was to investigate the effects of partial passive
      stretching (PPS) on peak torque (PT) and joint range of motion (ROM) in healthy
      subjects. METHODS: Twenty-two males (mean age 20.4+/-1.0 yrs, height 181.1+/-4.2
      cm and weight 75.8+/-6.8 kg) participated in the study. Quadriceps and hamstrings
      PT at different angular velocities was obtained on an isokinetic dynamometer.
      Standing leg method hop was tested for the stretched and unstretched leg. Each
      subject performed PPS for 20 seconds. The stretching procedure was repeated 5
      times for each muscle group. The whole stretching program lasted for 6 minutes
      and 20 seconds followed by 5 seconds resting period. RESULTS: Directly after the
      stretching procedure significant increases were observed of PT in quadriceps and
      hamstrings, however, only at 300o.s-1 (P<0.05). Joint ROM was increased in all
      subjects (P<0.05). The distance in single length hop was increased significantly
      in the stretched leg following stretching (P<0.05). No changes were observed in
      the unstretched leg. CONCLUSION: Our results indicated that the PPS altered ROM,
      maximal concentric isokinetic strength at high angle velocities and single length
      hop only for the stretched leg. These findings suggest that PPS may be an
      effective technique for enhancing muscle performance.

PMID- 24739292
TI  - Gender differences in carotid artery intima-media thickness and flow-mediated
      dilatation in young, physically active adults.
AB  - AIM: The purpose of this study was to examine gender differences (GD) in vascular
      structure and function and their relations to cardiovascular risk factors (CVD)
      in young, physically active adults. METHODS: Sixty-three apparently healthy,
      physically active adults (34 women, 29 men), aged 20.2+/-0.9 years, were involved
      in the study. RESULTS: Carotid artery intima-media thickness (IMT) values of both
      internal carotid (CI) and common carotid arteries (CC) were significantly (P<0.01
      and P<0.01) higher in men than in women (0.47+/-0.05 vs. 0.51+/-0.07 mm and
      0.45+/-0.07 vs. 0.49+/-0.07 mm, respectively). In women, CC-IMT was positively
      correlated with body fat mass, height and body mass; and CI-IMT was inversely
      correlated with systolic and diastolic blood pressure. In men, CI-IMT was
      positively correlated with body height, diastolic blood pressure and high
      sensitivity C-reactive protein (hsCRP). Relative values of flow-mediated
      dilatation (FMD) increased in women by 16.6%, in men by 13.7% after a 5-minute
      period of forearm ischemia, but absolute FMD was similar in men and women, 0.53+/
      0.25 vs. 0.53+/-0.14 mm, respectively. CONCLUSION: Values of CC IMT and CI IMT
      after adjustment to classical CVD risk factors remained strongly diversified with
      respect to gender, which confirmed the significance of gender as a conditional
      factor for atherosclerosis assessment. Some GD in vascular structure and function
      could be eliminated by adjusting for baseline artery diameter and/or subject's
      somatic features, i.e., body height. This study supports a need for additional
      studies focusing on understanding GD in vascular characteristics, which could
      lead to established better quality reference values and comprehend natural
      history of CVD in view of pathophysiological mechanisms underlying GD.

PMID- 24739293
TI  - Maturity-associated variation in change of direction and dribbling speed in early
      pubertal years and 5-year developmental changes in young soccer players.
AB  - AIM: The purpose of the current study was to assess the developmental changes in
      change of direction and dribbling speed in youth soccer players taking into
      account skeletal age (SA), maturity status, body size, estimated fat mass,
      aerobic endurance, lower limb explosive strength and annual volume of training.
      METHODS: Eighty-three male soccer players aged 10-15 years (SA) at baseline were
      annually followed over 5 years, resulting in an average 4.4 observations per
      player. After testing for multicollinearity, multi-level regression modeling was
      used to examine the longitudinal developmental changes on change of direction and
      dribbling speed. RESULTS: Maturity-associated variability was significant in
      change of direction and also dribbling speed among young soccer players aged 12
      14 years with better scores being performed by late maturers. Moreover, the
      predicted longitudinal scores for change of direction and dribbling speed
      improved with SA (P<0.01), SA2 (P<0.01) and skeletal maturity status entered as
      an additional developmental predictor (P<0.05). Estimated fat-free mass (P<0.01),
      aerobic endurance (P<0.01) and lower limb strength (P<0.01) were additional
      predictors in both models. The soccer-specific skill, dibbling speed, was also
      explained by annual volume of training (P<0.05). CONCLUSION: Skeletal maturity
      status explains inter-individual variability on maximal short-term run
      performances with and without the ball possession at early ages of participation
      in competitive soccer. The effects tend to persist across ages combined with
      longitudinal changes in body composition and functional fitness. In the
      particular case of the ball test, annual volume of training was also a
      longitudinal performance predictor.

PMID- 24739294
TI  - Effects of resistance training frequency on body composition and metabolics and
      inflammatory markers in overweight postmenopausal women.
AB  - The present study aimed to determine the importance of resistance training
      frequency on body composition and metabolics and inflammatory markers in
      sedentary overweight postmenopausal women (PW). Thirty subjects finished the
      resistance training-protocol (60% to 80% of 1-RM) and had all the evaluations
      (anthropometry, strength, food intake and biochemistry) done. Groups were
      assembled according to the week-frequency of attended sessions (G1-1 day/wk,
      N.=9; G2-2 days/wk, N.=11 and G3-3 days/wk, N.=10). The strength-training
      protocol resulted in similar changes on body composition and strength gains in
      all groups. However, the plasma markers responses differed among groups with G1
      showing an increase of both CRP and glucose, with G2 increasing CRP and G3
      keeping the baseline values. The results suggest that resistance exercise
      increases strength and muscle mass independently of the frequency. Moreover,
      highest resistance training frequency (3 days/week) prevented the rise of plasma
      glucose and CRP profile after 16 weeks of training in sedentary overweight PW. 

PMID- 24739295
TI  - Do epoch lengths affect adolescents' compliance with physical activity
      guidelines?
AB  - AIM: This study examined the effect of different epoch lengths (from 3 to 60 s)
      on (a) moderate to vigorous physical activity (MVPA), (b) 10 minutes bouts of
      MVPA and (c) compliance with World Health Organization (WHO) guidelines, as
      measured with an ActiGraph accelerometer. METHODS: A sample of 401 adolescents
      (14.48+/-0.69 years) wore a GT3X accelerometer to measure physical activity (PA)
      for 7 consecutive days. Data, originally collected in 1-s epoch(s), were then
      reintegrated into epochs of 3-, 5-, 10-, 15-, 30-, 45- and 60-s. RESULTS: The
      results showed a significant epoch effect (P=0.000) for time spent in MVPA, 10
      min bouts of MVPA and the extent of compliance with guidelines percentage of
      compliance of guidelines. Bland-Altman analysis showed good agreement between 5-
      and 10-, 5- and 15-, and 10- and 15-s data, both for MVPA and 10-min bouts of
      MVPA. CONCLUSION: Epidemiological studies should take into account the sampling
      interval to offer accurate conclusions with regard to levels of MVPA and the
      extent to which adolescents comply with guidelines. Shorter epochs, such as 5-,
      10- or 15-s are proposed for comparative studies carried out with adolescents in
      this area.

PMID- 24739296
TI  - Impact of insidious gastrointestinal blood loss on endurance performance in an
      elite rower.
AB  - Gastrointestinal (GI) blood loss is a possible reason for anemia in athletes. To
      quantify the impact on endurance performance, we present data of a world-class
      rower who developed anemia due to GI blood loss but maintained his training
      volume. Eight months after recording four normal hematological values over 6
      months, an anemic state was detected. Total hemoglobin mass (tHbmass) was reduced
      from 1267 g to 917 g (-28%) and [Hb] was reduced from 176 g/L to 122 g/L (-31%).
      Blood volume (BV) remained largely unchanged at 8162 mL and 8261 mL,
      respectively. VO2max was decreased from 5.8 L/min to 4.8 L/min (-17%), but
      remained ~0.4 L/min higher than calculated from tHbmass. Power at [lactate] 2
      mmol/L (P2) and 4 mmol/L (P4) decreased by 12% and 14%, respectively. Ten months
      after detection of the anemic state, the athlete had recovered and tHbmass (9%)
      as well as VO2max (3%), P2 (7%) and P4 (5%) were higher than before anemia. GI
      blood loss was most likely caused by the intake of non steroidal anti
      inflammatory drugs and/or a bleeding Meckel's diverticulum, the latter been
      diagnosed and surgically removed 3 years later after two rapid bleedings had
      occurred. Data demonstrate the impact of a tHbmass reduction leading to a
      substantial but mitigated decrease in submaximal performance and VO2max in an
      elite athlete. 10 months later, higher levels of tHbmass, VO2max, and endurance
      performance were observed. However, the underlying mechanisms for the apparent
      increase in tHbmass remain unclear. 

PMID- 24739297
TI  - Prediction of winning amateur boxers using pretournament reaction times.
AB  - AIM: Boxing requires agility and manual dexterity, which is associated with fast
      reflexes and reaction time. This study evaluated the relation between reaction
      times on cognitive tasks and competition outcomes in boxers. METHODS: The design
      was a prospective cohort study. Participants were collegiate amateur boxers who
      won at least one bout in a single elimination tournament. Optimal pre
      participation performance using a computerized cognitive assessment tool (CCAT,
      Axon Sports) and no significant deterioration in cognitive performance within 24
      hours post-bout was required to compete in future bouts. Winners were assumed to
      be motivated to perform optimally on testing. Performance on speed and accuracy
      measures were compared in winning and non-winning boxers. Pre-competition minutes
      of sparring and tournament seedings were recorded. RESULTS: There were 96
      eligible boxers who won at least one of 160 bouts. The mean age was 21.3 (SD 1.9)
      years (range 18.5-29.7). A significant improvement in mean reaction times as a
      function of advancement in the boxing tournament was observed. The 18 winning
      boxers who advanced to the finals had significantly faster mean reaction times at
      the baseline assessment before the competition began (speed composite z-score
      F(1,94)=4.14, P<0.05, effect size 0.54). Winners also had more sparring
      experience (Mann-Whitney U=302.5, P<0.001) and higher pre-competition rankings
      (Mann-Whitney U=288.5, P<0.001). CONCLUSION: In highly motivated amateur boxers,
      finalists performed significantly faster than those who failed to reach the
      finals on measures of pre-competition reaction time. These findings suggest that
      winners of boxing tournaments might be predicted using pre-competition measures
      of processing speed.

PMID- 24739298
TI  - Performance during cardiopulmonary exercise test and quality of life of long
      distance elderly runners and of non-exerciser elderly.
AB  - AIM: Regular physical exercises are associated to decreased morbidity and
      mortality, but their relationship with quality of life perception is still not
      well established. The aim of this paper was to compare cardiopulmonary exercise
      indicators of functional performance and quality of life (QOL) between a group of
      untrained elderly (GUE) and a group of trained elderly (GTE) in long-distance
      running. METHODS: GUE was made up of 19 individuals with mean age of 73.5+/-6.4
      years and GTE by 27 trained elderly with mean age of 73.1+/-4.3 years. All were
      submitted to cardiopulmonary and metabolic evaluation by expired gases analysis.
      Maximum physical capacity was determined on a motor-driven treadmill with
      continuous graded protocol and fixed slope of 1%. Quality of Life was evaluated
      in four domains (physical, psychological, social relations and environment) by
      Whoqol-Bref questionnaire (WHO) and quantified by total score for each domain.
      RESULTS: At maximal oxygen intake, GUE and GTE presented: VO2max: 27.0+/-5.4 vs.
      38.1+/-4.5 mL/[kg.min] (P<0.001); O2 pulse: 11.7+/-3.0 vs. 15.5+/-2.4 mL/bpm
      (P<0.001); running speed: 9.7+/-2.5 vs. 13.8+/-1.7 km/h (P<0.001) and tolerance
      time: 9.6+/-2.9 vs.14.8+/-4.4 min (P<0.001). QOL measured by Whoqol-Bref
      questionnaire in four domains for GUE and GTE was respectively: physical: 75.6+/
      13.6 vs. 80.6 +/-14.2 (P=0.210), psychological: 79.2+/-11.3 vs. 79.2+/-13.8
      (P=0.893), social relations: 74.6+/-14.3 vs. 74.7+/-19.1 (P=0.726), environment:
      61.4+/-15.9 vs. 69.0+/-15.5 (P=0.131). CONCLUSION: GTE cardiopulmonary
      performance was better as compared to GUE, and QOL of the elderly from both
      groups was not associated to cardiopulmonary exercise test performance.

PMID- 24739299
TI  - Effects of short- and long-term physical activity on DNA stability and oxidative
      stress status in young soccer players.
AB  - AIM: The aim of the study was to determine whether single soccer training is able
      to cause oxidative stress and DNA instability. We have also sought to investigate
      if adaptive response will be developed during 45 days training period and to what
      extent. METHODS: This study was conducted on 16 soccer players aged 18.13+/-0.35
      years. We used single cells gel electrophoresis (comet assay) to investigate
      leukocyte DNA stability. The results were presented as DNA score and percent of
      cells with medium and high damage. Oxidative status of our subjects was estimated
      through blood levels of superoxide anion, the thiobarbituric acid-reacting
      substances (TBARs), total antioxidant status (TAS), total oxidant status (TOS),
      prooxidant-antioxidant balance (PAB) and sulfhydryl-groups (SH-groups). RESULTS:
      During single soccer training, DNA score and percent of the cells with medium and
      high damage were increased after training but without significance. Sulphydryl
      groups (P=0.033), TOS (P=0.002) and PAB (P=0.045) were significantly lower after
      training. After 45 days training period DNA score was decreased but with no
      significance. However, percent of cells with medium and high damage was
      significantly lower (P=0.01). TOS (P=0.001) and MDA (P=0.038) levels were also
      significantly lower, while sulphydryl-groups levels were significantly higher
      (P=0.006). CONCLUSION: This study demonstrated that single soccer training had
      not compromised DNA stability. Possible development of oxidative stress was
      effectively neutralized by very well preserved antioxidative mechanisms. It was
      also shown that during 45 days adaptive response was induced. All measured
      parameters should be considered as useful information on oxidative status of
      trainees.

PMID- 24739300
TI  - Effects of continuous and intermittent aerobic exercise upon mRNA expression of
      metabolic genes in human skeletal muscle.
AB  - AIM: It is known that intermittent aerobic exercise training program is more
      efficient for the improvement of aerobic performance than continuous one but
      molecular mechanisms of such effects are purely understood. The aim of the
      present study was to compare gene expression of mitochondrial biogenesis
      regulators (peroxisome proliferator-activated receptor gamma coactivator 1alpha
      (PGC-1alpha), mitochondrial transcription factors A (TFAM) and B2 (TFB2M) and
      genes involved in exercise-induced catabolic events (forkhead box O1 (FOXO1) and
      Atrogin-1) in human skeletal muscle after single continuous (CE) and intermittent
      (IE) aerobic exercise sessions, equalized thoroughly in duration and mean power
      output. METHODS: Twelve physically active males performed CE (workload at lactate
      threshold [LT], 50 min) or IE ([3 min 81% LT+2 min 125% LT]x10). The biopsies
      were taken from m. vastus lateralis before and 1 h, 3 h, 5 h after the exercise.
      RESULTS: The IE induced a 2-fold greater increase of PGC-1alpha and TFAM gene
      expression after 3 h and 5 h of recovery than CE. The increments of Atrogin-1
      mRNA abundance were observed 3 and 5 h after IE only. The increments in FOXO1
      mRNA level were revealed 1 h and 3 h after the IE and 3 h after the CE.
      CONCLUSION: The results of the study suggest that higher potential of IE for the
      improvement of mitochondrial biogenesis than CE associated with more pronounced
      increase of PGC-1alpha and TFAM mRNA expression. Along with that, IE induces a
      higher increment of expression of FOXO1 and Atrogin-1 genes involved with
      exercise-induced catabolic events compared to CE.

PMID- 24739301
TI  - Running out of brain.
AB  - Stroke is the third most common cause of death after coronary artery disease and
      cancer in the UK, and running is a popular form of exercise, and increasingly,
      people are participating in large scale endurance events such as marathons and
      half-marathons. We describe here two cases of young men suffering a stroke after
      running a marathon and who were subsequently found to have a patent foramen ovale
      (PFO). We have reviewed the existing literature concerning stroke in those
      undertaking long-distance running, and suggest why PFO may have been important
      etiologically in our two patients. We tentatively suggest that individuals with a
      PFO who engage in long distance running may be at increased risk of stroke,
      independent of other cerebrovascular risk factors. 

PMID- 24739302
TI  - Arabidopsis genes, AtNPR1, AtTGA2 and AtPR-5, confer partial resistance to
      soybean cyst nematode (Heterodera glycines) when overexpressed in transgenic
      soybean roots.
AB  - BACKGROUND: Extensive studies using the model system Arabidopsis thaliana to
      elucidate plant defense signaling and pathway networks indicate that salicylic
      acid (SA) is the key hormone triggering the plant defense response against
      biotrophic and hemi-biotrophic pathogens, while jasmonic acid (JA) and
      derivatives are critical to the defense response against necrotrophic pathogens.
      Several reports demonstrate that SA limits nematode reproduction. RESULTS: Here
      we translate knowledge gained from studies using Arabidopsis to soybean. The
      ability of thirty-one Arabidopsis genes encoding important components of SA and
      JA synthesis and signaling in conferring resistance to soybean cyst nematode
      (SCN: Heterodera glycines) are investigated. We demonstrate that overexpression
      of three of thirty-one Arabidoposis genes in transgenic soybean roots of
      composite plants decreased the number of cysts formed by SCN to less than 50% of
      those found on control roots, namely AtNPR1(33%), AtTGA2 (38%), and AtPR-5 (38%).
      Three additional Arabidopsis genes decreased the number of SCN cysts by 40% or
      more: AtACBP3 (53% of the control value), AtACD2 (55%), and AtCM-3 (57%). Other
      genes having less or no effect included AtEDS5 (77%), AtNDR1 (82%), AtEDS1
      (107%), and AtPR-1 (80%), as compared to control. Overexpression of AtDND1
      greatly increased susceptibility as indicated by a large increase in the number
      of SCN cysts (175% of control). CONCLUSIONS: Knowledge of the pathogen defense
      system gained from studies of the model system, Arabidopsis, can be directly
      translated to soybean through direct overexpression of Arabidopsis genes. When
      the genes, AtNPR1, AtGA2, and AtPR-5, encoding specific components involved in SA
      regulation, synthesis, and signaling, are overexpressed in soybean roots,
      resistance to SCN is enhanced. This demonstrates functional compatibility of some
      Arabidopsis genes with soybean and identifies genes that may be used to engineer
      resistance to nematodes.

PMID- 24739303
TI  - Epigenetic regulation of aortic remodeling in hyperhomocysteinemia.
AB  - Hyperhomocysteinemia (HHcy) is prevalent in patients with hypertension and is an
      independent risk factor for aortic pathologies. HHcy is known to cause an
      imbalance between matrix metalloproteinases (MMPs) and tissue inhibitors of
      metalloproteinases (TIMPs), leading to the accumulation of collagen in the aorta
      and resulting in stiffness and development of hypertension. Although the exact
      mechanism of extracellular matrix (ECM) remodeling is unclear, emerging evidence
      implicates epigenetic regulation involving DNA methylation. Our purpose was to
      investigate whether 5-aza-2'-deoxycytidine (Aza), a DNA methyltransferase (DNMT1)
      inhibitor, reduces high blood pressure (BP) by regulating aortic ECM remodeling
      in HHcy. Wild-type and cystathionine beta-synthase (CBS)(+/-) HHcy mice were
      treated with Aza (0.5 mg/kg body weight). In HHcy mice, Aza treatment normalized
      the plasma homocysteine (Hcy) level and BP. Thoracic and abdominal aorta
      ultrasound revealed a reduction in the resistive index and wall-to-lumen ratio.
      Vascular response to phenylephrine, acetylcholine, and sodium nitroprusside
      improved after Aza in HHcy mice. Histology showed a marked reduction in collagen
      deposition in the aorta. Aza treatment decreased the expression of DNMT1, MMP9,
      TIMP1, and S-adenosyl homocysteine hydrolase (SAHH) and upregulated methylene
      tetrahydrofolate reductase (MTHFR). We conclude that reduction of DNA methylation
      by Aza in HHcy reduces adverse aortic remodeling to mitigate hypertension.

PMID- 24739304
TI  - Follicle-stimulating hormone synthesis and fertility depend on SMAD4 and FOXL2.
AB  - Follicle-stimulating hormone (FSH) is an essential regulator of gonadal function
      and fertility. Loss-of-function mutations in the FSHB/Fshb gene cause
      hypogonadotropic hypogonadism in humans and mice. Both gonadotropin-releasing
      hormone (GnRH) and activins, members of the transforming growth factor beta
      (TGFbeta) superfamily, stimulate FSH synthesis; yet, their relative roles and
      mechanisms of action in vivo are unknown. Here, using conditional gene-targeting,
      we show that the canonical mediator of TGFbeta superfamily signaling, SMAD4, is
      absolutely required for normal FSH synthesis in both male and female mice.
      Moreover, when the Smad4 gene is ablated in combination with its DNA binding
      cofactor Foxl2 in gonadotrope cells, mice make essentially no FSH and females are
      sterile. Indeed, the phenotype of these animals is remarkably similar to that of
      Fshb-knockout mice. Not only do these results establish SMAD4 and FOXL2 as
      essential master regulators of Fshb transcription in vivo, they also suggest that
      activins, or related ligands, could play more important roles in FSH synthesis
      than GnRH.

PMID- 24739305
TI  - PopGenome: an efficient Swiss army knife for population genomic analyses in R.
AB  - Although many computer programs can perform population genetics calculations,
      they are typically limited in the analyses and data input formats they offer; few
      applications can process the large data sets produced by whole-genome
      resequencing projects. Furthermore, there is no coherent framework for the easy
      integration of new statistics into existing pipelines, hindering the development
      and application of new population genetics and genomics approaches. Here, we
      present PopGenome, a population genomics package for the R software environment
      (a de facto standard for statistical analyses). PopGenome can efficiently process
      genome-scale data as well as large sets of individual loci. It reads DNA
      alignments and single-nucleotide polymorphism (SNP) data sets in most common
      formats, including those used by the HapMap, 1000 human genomes, and 1001
      Arabidopsis genomes projects. PopGenome also reads associated annotation files in
      GFF format, enabling users to easily define regions or classify SNPs based on
      their annotation; all analyses can also be applied to sliding windows. PopGenome
      offers a wide range of diverse population genetics analyses, including neutrality
      tests as well as statistics for population differentiation, linkage
      disequilibrium, and recombination. PopGenome is linked to Hudson's MS and Ewing's
      MSMS programs to assess statistical significance based on coalescent simulations.
      PopGenome's integration in R facilitates effortless and reproducible downstream
      analyses as well as the production of publication-quality graphics. Developers
      can easily incorporate new analyses methods into the PopGenome framework.
      PopGenome and R are freely available from CRAN (http://cran.r-project.org/) for
      all major operating systems under the GNU General Public License. 

PMID- 24739306
TI  - RetrogeneDB--a database of animal retrogenes.
AB  - Retrocopies of protein-coding genes, reverse transcribed and inserted into the
      genome copies of mature RNA, have commonly been categorized as pseudogenes with
      no biological importance. However, recent studies showed that they play important
      role in the genomes evolution and shaping interspecies differences. Here, we
      present RetrogeneDB, a database of retrocopies in 62 animal genomes. RetrogeneDB
      contains information about retrocopies, their genomic localization, parental
      genes, ORF conservation, and expression. To our best knowledge, this is the most
      complete retrocopies database providing information for dozens of species
      previously never analyzed in the context of protein-coding genes retroposition.
      The database is available at http://retrogenedb.amu.edu.pl. 

PMID- 24739307
TI  - Signatures of natural selection on mutations of residues with multiple
      posttranslational modifications.
AB  - Posttranslational modifications (PTMs) regulate molecular structures and
      functions of proteins by covalently binding to amino acids. Hundreds of thousands
      of PTMs have been reported for the human proteome, with multiple PTMs known to
      affect tens of thousands of lysine (K) residues. Our molecular evolutionary
      analyses show that K residues with multiple PTMs exhibit greater conservation
      than those with a single PTM, but the difference is rather small. In contrast,
      short-term evolutionary trends revealed in an analysis of human population
      variation exhibited a much larger difference. Lysine residues with three PTMs
      show 1.8-fold enrichment of Mendelian disease-associated variants when compared
      with K residues with two PTMs, with the latter showing 1.7-fold enrichment of
      these variants when compared with the K residues with one PTM. Rare polymorphisms
      in humans show a similar trend, which suggests much greater negative selection
      against mutations of K residues with multiple PTMs within population. Conversely,
      common polymorphisms are overabundant at unmodified K residues and at K residues
      with fewer PTMs. The observed difference between inter- and intraspecies patterns
      of purifying selection on residues with PTMs suggests extensive species-specific
      drifting of PTM positions. These results suggest that the functionality of a
      protein is likely conserved, without necessarily conserving the PTM positions
      over evolutionary time. 

PMID- 24739309
TI  - The relationship between sleep disorders and testosterone.
AB  - PURPOSE OF REVIEW: This review describes evolving concepts and recent data on the
      relationship between serum testosterone levels and normal and disordered sleep.
      RECENT FINDINGS: Sex-related differences in circadian rhythms and sleep
      physiology are in part due to organizational and activational effects of sex
      steroids. Testosterone affects the organization of circadian rhythms and the
      timing, but not the duration, of sleep. Increasing testosterone during puberty
      leads to later bedtimes. The diurnal variation in testosterone depends on sleep
      rather than circadian rhythm or season. Pubertal onset is heralded, well before
      virilization, by a luteinizing hormone level at least 3.7 U/l during sleep. Total
      sleep deprivation lowers testosterone, but sleep restriction only does so if it
      occurs in the first half of the night. The recovery of testosterone from sleep
      disruption is impaired in old as compared with young rodents. In men with
      obstructive sleep apnoea (OSA), low testosterone is related to obesity rather
      than the OSA itself, and improves with weight loss but inconsistently with
      continuous positive airway pressure (CPAP). Testosterone treatment only
      transiently worsens severity of OSA, which need not be considered a
      contraindication to its use. SUMMARY: Testosterone treatment is unlikely to
      benefit sleep in men with secondary hypogonadism, for example due to obesity or
      depression, in contrast to the management of the underlying abnormality.

PMID- 24739308
TI  - Origin of robustness in generating drug-resistant malaria parasites.
AB  - Biological robustness allows mutations to accumulate while maintaining functional
      phenotypes. Despite its crucial role in evolutionary processes, the mechanistic
      details of how robustness originates remain elusive. Using an evolutionary
      trajectory analysis approach, we demonstrate how robustness evolved in malaria
      parasites under selective pressure from an antimalarial drug inhibiting the
      folate synthesis pathway. A series of four nonsynonymous amino acid substitutions
      at the targeted enzyme, dihydrofolate reductase (DHFR), render the parasites
      highly resistant to the antifolate drug pyrimethamine. Nevertheless, the stepwise
      gain of these four dhfr mutations results in tradeoffs between pyrimethamine
      resistance and parasite fitness. Here, we report the epistatic interaction
      between dhfr mutations and amplification of the gene encoding the first upstream
      enzyme in the folate pathway, GTP cyclohydrolase I (GCH1). gch1 amplification
      confers low level pyrimethamine resistance and would thus be selected for by
      pyrimethamine treatment. Interestingly, the gch1 amplification can then be co
      opted by the parasites because it reduces the cost of acquiring drug-resistant
      dhfr mutations downstream in the same metabolic pathway. The compensation of
      compromised fitness by extra GCH1 is an example of how robustness can evolve in a
      system and thus expand the accessibility of evolutionary trajectories leading
      toward highly resistant alleles. The evolution of robustness during the gain of
      drug-resistant mutations has broad implications for both the development of new
      drugs and molecular surveillance for resistance to existing drugs. 

PMID- 24739310
TI  - Genetic testing in the clinical care of patients with pheochromocytoma and
      paraganglioma.
AB  - PURPOSE OF REVIEW: Paraganglioma and pheochromocytoma (PGL/PCC) are tumours of
      neural crest origin that can present along a clinical spectrum ranging from
      apparently sporadic, isolated tumours to a more complex phenotype of one or
      multiple tumours in the context of other clinical features and family history
      suggestive of a defined hereditary syndrome. Genetic testing for hereditary
      PGL/PCC can help to confirm a genetic diagnosis for sporadic and syndromic cases.
      Informative genetic testing serves to clarify future risks for the patient and
      family members. RECENT FINDINGS: Genetic discovery in the last decade has
      identified new PGL/PCC susceptibility loci. We summarize a contemporary approach
      adopted in our programme for genetic evaluation, testing and prospective
      management involving biochemical monitoring and imaging for hereditary PGL/PCC. A
      clinical vignette is presented to illustrate our practice. SUMMARY: Current
      estimates that up to 40% of PGL/PCC are associated with germline mutations have
      implications for genetic testing recommendations. Prospective management of
      patients with defined hereditary susceptibility is based on established
      guidelines for well characterized syndromes. Management of tumour risk for rare
      syndromes, newly defined genetic associations and undefined genetic
      susceptibility in the setting of significant family history presents a challenge.
      Sustained discovery of new PGL/PCC genes underscores the need for a practice of
      continued genetic evaluation for patients with uninformative results. All
      patients with PGL/PCC should undergo genetic testing to identify potential
      hereditary tumour susceptibility.

PMID- 24739311
TI  - Primary bilateral macronodular adrenal hyperplasia.
AB  - PURPOSE OF REVIEW: Primary bilateral macronodular adrenal hyperplasia is a rare
      cause of Cushing's syndrome and is more often diagnosed as bilateral adrenal
      incidentalomas with subclinical cortisol production. We summarize the recent
      insights concerning its epidemiology, diagnosis, genetics, pathophysiology, and
      therapeutic options. RECENT FINDINGS: Recent publications have modified our
      notions on the genetics and pathophysiology of bilateral macronodular adrenal
      hyperplasia. Combined germline and somatic mutations of armadillo repeat
      containing 5 gene were identified in familial cases, in approximately 50% of
      apparently sporadic cases and in the relatives of index cases; genetic testing
      should allow early diagnosis in the near future. The recent finding of ectopic
      adrenocortical production of adrenocorticotropic hormone in clusters of bilateral
      macronodular adrenal hyperplasia tissues and its regulation by aberrant hormone
      receptors opens new horizons for eventual medical therapy using melanocortin-2
      receptor and G-protein-coupled receptor antagonists. Finally, some medical and
      surgical treatments have been updated. SUMMARY: Recent findings indicate that
      bilateral macronodular adrenal hyperplasia is more frequently genetically
      determined than previously believed. Considering the role of paracrine
      adrenocorticotropic hormone production on cortisol secretion, the previous
      nomenclature of adrenocorticotropic hormone-independent macronodular adrenal
      hyperplasia appears inappropriate, and this disease should now be named primary
      bilateral macronodular adrenal hyperplasia.

PMID- 24739312
TI  - Novel genes in primary aldosteronism.
AB  - PURPOSE OF REVIEW: Novel high-throughput genetic techniques have increased the
      pace of discoveries in the field of primary aldosteronism. Mutations in the
      potassium channel gene KCNJ5 are a cause of familial and sporadic forms of
      primary aldosteronism with around 30-40% of aldosterone-producing adenomas being
      affected by somatic mutations. RECENT FINDINGS: Exome sequencing of tumors
      without KCNJ5 mutations revealed genetic alterations in the ATPases ATP1A1 and
      ATP2B3, with a combined prevalence of 5-7%. Mutations in the gene encoding a
      subunit of the Ca channel Cav1.3 (CACNA1D) were described with a prevalence of 5
      8%. In addition, a new syndrome consisting of primary aldosteronism, seizures,
      and neuromuscular disease with germline CACNA1D mutations could be identified.
      All these genetic variants enhance Ca-mediated signalling and steroidogenesis in
      affected glomerulosa cells and provide the molecular basis for autonomous
      aldosterone secretion. Furthermore, the pattern of genetic alterations allows for
      subgrouping of patient cohorts with potentially distinct clinical features
      including sex and age distribution as well as endocrine and cardiovascular
      endpoints. SUMMARY: Altogether in around 50% of aldosterone-producing adenomas, a
      somatic point mutation can be identified as the underlying genetic cause. These
      findings will provide the framework for potential identification of new
      biomarkers and therapeutic targets of this most common form of secondary
      hypertension.

PMID- 24739313
TI  - Genetic testing and counselling for male infertility.
AB  - PURPOSE OF REVIEW: Genetic disorders can be identified in about 15% of cases of
      male infertility. With the widespread application of assisted reproductive
      technology, infertile patients are now given the possibility of having their
      biological children; however, a genetic risk exists for assisted reproductive
      technology-born offspring, implying the necessity for future parents to be
      appropriately informed about potential consequences. In this review, we provide
      current recommendations on clinical genetic testing and genetic counselling.
      RECENT FINDINGS: New insights are presented concerning Klinefelter syndrome, X
      and Y chromosome-linked deletions, monogenic diseases and pharmacogenetics.
      SUMMARY: As for Klinefelter patients, novel preventive measures to preserve
      fertility have been proposed although they are not yet applicable in the routine
      setting. Y-chromosome deletions have both diagnostic and prognostic values and
      their testing is advised to be performed according to the new European Academy of
      Andrology/European Molecular Genetics Quality Network guidelines. Among monogenic
      diseases, major advances have been obtained in the identification of novel genes
      of hypogonadotrophic hypogonadism. Pharmacogenetic approaches of hormonal
      treatment in infertile men with normal values of follicle-stimulating hormone
      (FSH) are promising and based on FSHR and FSHB polymorphisms. X chromosome-linked
      deletions are relevant for impaired spermatogenesis. In about 40% of male
      infertility, the cause is unknown and novel genetic factors are expected to be
      discovered in the near future.

PMID- 24739314
TI  - Clinical applications of LC-MS sex steroid assays: evolution of methodologies in
      the 21st century.
AB  - PURPOSE OF REVIEW: The purpose of this review is to summarize why and how liquid
      chromatography tandem mass spectrometry (LC-MS/MS) is increasingly replacing
      other methodologies for the measurement of sex steroids. RECENT FINDINGS:
      Measurement of sex steroids, particularly testosterone and estradiol, is
      important for diagnosis or management of a host of conditions (e.g. disorders of
      puberty, hypogonadism, polycystic ovary syndrome, amenorrhea, and tumors of
      ovary, testes, breast and prostate). Historically, metabolites of testosterone
      and estradiol were measured as ketosteroids in urine using colorimetric assays
      that lacked sensitivity and specificity due to endogenous and exogenous
      interferences. Extracted competitive manual radio-immunoassays provided improved,
      but still imperfect, specificity, and offered increased sensitivity. As testing
      demand increased, they were displaced by automated immunoassays. These offered
      better throughput and precision, but suffered worse specificity problems.
      Moreover, agreement between different immunoassays has often been poor and they
      are all compromised by a limited dynamic measurement range. To overcome these
      problems, LC-MS/MS methods have been developed and validated for quantitation of
      sex steroids. These methods reduce interferences, provide better specificity,
      improve dynamic range, and reduce between-method bias. SUMMARY: Endocrine Society
      and Urology Society guidelines have highlighted the limitations of the
      immunoassays for sex steroids and have provided convincing evidence that mass
      spectrometric methods are preferable for measurement of sex steroid hormones. In
      this review, we describe LC-MS/MS methods for measurement of testosterone and
      estradiol.

PMID- 24739315
TI  - Experimental study on retroperitoneal artery bleeding with contrast-enhanced
      ultrasound.
AB  - BACKGROUND: We lack noninvasive and effective methods for evaluating origin of
      pelvic hemorrhage. Contrast-enhanced ultrasound (CEUS) may be a prospective
      method. OBJECTIVE: We aimed to investigate the diagnostic value of CEUS on
      external iliac artery (EIA) bleeding in rabbits. METHODS: Fourteen rabbits were
      evenly divided into small- and big-crevasse groups. EIAs of rabbits in the small
      crevasse group were punctured with a 12-G needle via femoral arterial
      cannulation. After puncture, the crevasse of EIAs of rabbits in the big-crevasse
      group was enlarged with a dilator. CEUS was performed 2, 10, and 40 min after
      artery injury. Digital subtraction angiography (DSA) was performed 20 and 30 min
      after injury. RESULTS: A massive enhancement region in the retroperitoneal space
      adjacent to the injured EIA and a jet at the site of the crevasse were observed
      on intravenous CEUS within 2 min after injury in all rabbits of the two groups.
      Contrast-agent extravasation verified by DSA was detected in all rabbits of the
      big-crevasse group on CEUS of 10 min and 40 min after injury with significant
      lower velocity (p < 0.05). In the small-crevasse group, four rabbits displayed
      contrast-agent extravasation on CEUS of 10 min and none on CEUS of 40 min after
      injury, however, six rabbits and one rabbit exhibited contrast-agent
      extravasation on DSA of 20 min and 30 min after injury, respectively.
      CONCLUSIONS: The accuracy of CEUS in detecting active bleeding of peritoneal
      artery was high. Pulsed Doppler guided by CEUS was able to distinguish arterial
      from venous blood flow and to exhibit the velocity changes.

PMID- 24739316
TI  - The eight-drop method for nasogastric tube insertion.

PMID- 24739317
TI  - Small but mighty: unusual cause of massive mediastinal hematoma.

PMID- 24739318
TI  - Prednisone for emergency department low back pain: a randomized controlled trial.
AB  - BACKGROUND: Although oral corticosteroids are commonly given to emergency
      department (ED) patients with musculoskeletal low back pain (LBP), there is
      little evidence of benefit. OBJECTIVE: To determine if a short course of oral
      corticosteroids benefits LBP ED patients. METHODS:  DESIGN: Randomized, double
      blind, placebo-controlled trial. SETTING: Suburban New Jersey ED with 80,000
      annual visits. PARTICIPANTS: 18-55-year-olds with moderately severe
      musculoskeletal LBP from a bending or twisting injury <= 2 days prior to
      presentation. Exclusion criteria were suspected nonmusculoskeletal etiology,
      direct trauma, motor deficits, and local occupational medicine program visits.
      PROTOCOL: At ED discharge, patients were randomized to either 50 mg prednisone
      daily for 5 days or identical-appearing placebo. Patients were contacted after 5
      days to assess pain on a 0-3 scale (none, mild, moderate, severe) as well as
      functional status. RESULTS: The prednisone and placebo groups had similar
      demographics and initial and discharge ED pain scales. Of the 79 patients
      enrolled, 12 (15%) were lost to follow-up, leaving 32 and 35 patients in the
      prednisone and placebo arms, respectively. At follow-up, the two arms had similar
      pain on the 0-3 scale (absolute difference 0.2, 95% confidence interval [CI] 
      0.2, 0.6) and no statistically significant differences in resuming normal
      activities, returning to work, or days lost from work. More patients in the
      prednisone than in the placebo group sought additional medical treatment (40% vs.
      18%, respectively, difference 22%, 95% CI 0, 43%). CONCLUSION: We detected no
      benefit from oral corticosteroids in our ED patients with musculoskeletal LBP.

PMID- 24739319
TI  - Statistical properties of single-marker tests for rare variants.
AB  - With the dramatic technological developments of genome-wide association single
      nucleotide polymorphism (SNP) chips and next generation sequencing, human
      geneticists now have the ability to assay genetic variation at ever-rarer allele
      frequencies. To fully understand the impact of these rare variants on common,
      complex diseases, we must be able to accurately assess their statistical
      significance. However, it is well established that classical association tests
      are not appropriate for the analysis of low-frequency variation, giving spurious
      findings when observed counts are too few. To further our understanding of the
      asymptotic properties of traditional association tests, we conducted a range of
      simulations of a typical rare variant (~1%) under the null hypothesis and tested
      the allelic chi2, Cochran-Armitage trend, Wald, and Fisher's exact tests. We
      demonstrate that rare variation shows marked deviation from the expected
      distributional behavior for each test, with fewer minor alleles corresponding to
      a greater degree of test statistics deflation. The effect becomes more pronounced
      at progressively smaller alpha levels. We also show that the Wald test is
      particularly deflated at alpha levels consistent with genome-wide association
      significance, much more so than the other association tests considered. In
      general, these classical association tests are inappropriate for the analysis of
      variants for which the minor allele is observed fewer than 80 times, largely
      irrespective of sample size. 

PMID- 24739320
TI  - Journal club: Magnetic resonance imaging-guided focused laser interstitial
      thermal therapy for intracranial lesions: single-institution series.

PMID- 24739321
TI  - Response to journal club: Magnetic resonance imaging-guided focused laser
      interstitial thermal therapy for intracranial lesions: single-institution series.

PMID- 24739325
TI  - Treat-to-target in systemic lupus erythematosus: recommendations from an
      international task force.
AB  - The principle of treating-to-target has been successfully applied to many
      diseases outside rheumatology and more recently to rheumatoid arthritis.
      Identifying appropriate therapeutic targets and pursuing these systematically has
      led to improved care for patients with these diseases and useful guidance for
      healthcare providers and administrators. Thus, an initiative to evaluate possible
      therapeutic targets and develop treat-to-target guidance was believed to be
      highly appropriate in the management of systemic lupus erythematosus (SLE)
      patients as well. Specialists in rheumatology, nephrology, dermatology, internal
      medicine and clinical immunology, and a patient representative, contributed to
      this initiative. The majority convened on three occasions in 2012-2013. Twelve
      topics of critical importance were identified and a systematic literature review
      was performed. The results were condensed and reformulated as recommendations,
      discussed, modified and voted upon. The finalised bullet points were analysed for
      degree of agreement among the task force. The Oxford Centre level of evidence
      (LoE, corresponding to the research questions) and grade of recommendation (GoR)
      were determined for each recommendation. The 12 systematic literature searches
      and their summaries led to 11 recommendations. Prominent features of these
      recommendations are targeting remission, preventing damage and improving quality
      of life. LoE and GoR of the recommendations were variable but agreement was >0.9
      in each case. An extensive research agenda was identified, and four overarching
      principles were also agreed upon. Treat-to-target-in-SLE (T2T/SLE)
      recommendations were developed by a large task force of multispecialty experts
      and a patient representative. It is anticipated that 'treating-to-target' can and
      will be applicable to the care of patients with SLE. 

PMID- 24739326
TI  - Decreases in diagnostic delay are supported by sensitivity analyses.

PMID- 24739328
TI  - A simplified up-down method (SUDO) for measuring mechanical nociception in
      rodents using von Frey filaments.
AB  - BACKGROUND: The measurement of mechanosensitivity is a key method for the study
      of pain in animal models. This is often accomplished with the use of von Frey
      filaments in an up-down testing paradigm. The up-down method described by Chaplan
      et al. (J Neurosci Methods 53:55-63, 1994) for mechanosensitivity testing in
      rodents remains one of the most widely used methods for measuring pain in
      animals. However, this method results in animals receiving a varying number of
      stimuli, which may lead to animals in different groups receiving different
      testing experiences that influences their later responses. To standardize the
      measurement of mechanosensitivity we developed a simplified up-down method (SUDO)
      for estimating paw withdrawal threshold (PWT) with von Frey filaments that uses a
      constant number of five stimuli per test. We further refined the PWT calculation
      to allow the estimation of PWT directly from the behavioral response to the fifth
      stimulus, omitting the need for look-up tables. RESULTS: The PWT estimates
      derived using SUDO strongly correlated (r > 0.96) with the PWT estimates
      determined with the conventional up-down method of Chaplan et al., and this
      correlation remained very strong across different levels of tester experience,
      different experimental conditions, and in tests from both mice and rats. The two
      testing methods also produced similar PWT estimates in prospective behavioral
      tests of mice at baseline and after induction of hyperalgesia by intraplantar
      capsaicin or complete Freund's adjuvant. CONCLUSION: SUDO thus offers an
      accurate, fast and user-friendly replacement for the widely used up-down method
      of Chaplan et al.

PMID- 24739327
TI  - Basiliximab may improve the survival rate of rapidly progressive interstitial
      pneumonia in patients with clinically amyopathic dermatomyositis with anti-MDA5
      antibody.

PMID- 24739329
TI  - Pre-course simulation as a predictor of satisfaction with an emergency nursing
      clinical course.
AB  - Recent research suggests that simulation education can effectively improve
      nursing students' practical competence and can enhance educational outcomes. But
      very few studies have identified the relationships between pre-course simulation
      and course satisfaction. The purpose of this study was to determine whether pre
      course simulations and other advanced learning modalities (i.e. pre-course e
      learning, observation, and clinical placement skill performance) predicted
      students' satisfaction with an emergency nursing clinical course. Second-year
      Korean nursing students (N = 284) participated in an integrated clinical course
      consisting of self-directed pre-course e-learning, a 2-hour pre-course
      simulation, and an 80-hour emergency room clinical placement with observation.
      Multiple regression analyses found that pre-course simulation, clinical placement
      skill performance, observation during the clinical placement, and pre-course e
      learning accounted for 47.2% of the variance in course satisfaction. Notably, pre
      course simulation made the largest contribution to course satisfaction,
      accounting for 29.1% of the variance. Pre-course simulation, skill performance,
      observation, and pre-course e-learning all significantly influenced learner
      satisfaction. Findings suggest that integrating simulation into the clinical
      curriculum may enhance clinical course satisfaction.

PMID- 24739330
TI  - Motivation and international clinical placements: shifting nursing students to a
      global citizenship perspective.
AB  - Nursing programs are increasingly offering international clinical experiences as
      part of nursing curricula. The purpose of this study was to understand what
      motivates student nurses to take part in these experiences. Related to
      motivation, student awareness of emerging nursing discourses on global
      citizenship was also examined. As part of a qualitative study, nine undergraduate
      nursing students were interviewed about their motivations for choosing a clinical
      placement to a low-income country. While students appeared to have a sincere
      desire to make a difference, closer examination of the data revealed that the
      majority approached their international clinical placement in ways that could be
      construed as paternalistic to some degree, rather than reflective of broader
      professional imperatives such as social justice. This finding suggests that
      additional education preparation may be needed prior to these experiences; global
      citizenship frameworks may be helpful in shifting perspectives towards a more
      critical enquiry of global issues.

PMID- 24739331
TI  - Early intervention for first-episode psychosis: broadening the scope of economic
      estimates.
AB  - AIM: To explore the economic impacts of early intervention in England on outcomes
      and costs for people with first-episode psychosis. METHODS: Three decision
      analytical models were constructed to compare treatment by early intervention for
      first-episode psychosis with standard care in relation to employment, education,
      homicide and suicide. Data on effectiveness and costs were taken from previous
      studies and expert opinion. Sensitivity analyses tested the robustness of
      assumptions. RESULTS: Our models indicate that early intervention demonstrates
      savings of L2087 per person over 3 years from improved employment and education
      outcomes. In addition, the annual costs over 10 years related to homicide after
      early intervention were L80 lower than for standard care. There were also annual
      savings of L957 per person for early intervention over 4 years compared to
      standard care as a result of suicides averted. CONCLUSIONS: Not only can
      investment in early intervention help reduce some of the long-term costs and
      consequences of mental disorders to the health-care system. In addition, there
      are broader economic benefits that strengthen the potential cost savings to
      society.

PMID- 24739332
TI  - Prognostic values of clinical lymph node metastasis and macroscopic extrathyroid
      extension in papillary thyroid carcinoma.
AB  - In papillary thyroid carcinoma (PTC), macroscopic extrathyroid extension (Ex) and
      clinical node metastasis (N) are prominent prognostic factors. Ex is divided into
      two grades in the UICC TNM classification: minimal and massive Ex. Massive Ex
      significantly affects patients' prognoses, whereas minimal Ex has little
      prognostic value. N is also divided into two grades in the TNM classification:
      N1a and N1b, depending on the location of metastasis, with N1b graded higher than
      N1a. However, massive Ex and/or N-positive PTC includes patients with a wide
      range of biological characteristics and prognoses, depending on their degrees of
      Ex and N. Other clinicopathological features such as age, gender, and tumor size
      also influence the prognosis. In evaluations of the biological characteristics of
      PTC patients with Ex and/or N, we should consider the degrees and relationships
      of Ex and N with other clinicopathological features. 

PMID- 24739333
TI  - Clinical effects of ghrelin on gastrointestinal involvement in patients with
      systemic sclerosis.
AB  - The majority of patients with systemic sclerosis (SSc) have gastrointestinal (GI)
      tract involvement, but therapies using prokinetic agents are usually
      unsatisfactory. Ghrelin stimulates gastric motility in healthy human volunteers.
      In this study, we investigated whether ghrelin could improve gastric emptying in
      patients with gastrointestinal symptoms due to SSc. The study was performed in a
      randomized, double-blind, placebo-controlled crossover fashion on two occasions.
      Ten SSc patients with GI tract involvement received an infusion of either ghrelin
      (5.0 MUg/kg) or saline, and gastric emptying rate was evaluated by 13C-acetic
      acid breath test. Gastric emptying was significantly accelerated by ghrelin
      infusion in patients with SSc (ghrelin vs. saline: 43.3 +/- 11.4 min vs. 53.4 +/-
      5.4 min, P=0.03). No serious adverse effects were observed. Our results suggest
      that ghrelin might represent a new therapeutic approach for GI tract involvement
      in patients with SSc.

PMID- 24739335
TI  - Reducing the impact of insulin sensitivity variability on glycaemic outcomes
      using separate stochastic models within the STAR glycaemic protocol.
AB  - BACKGROUND: The metabolism of critically ill patients evolves dynamically over
      time. Post critical insult, levels of counter-regulatory hormones are
      significantly elevated, but decrease rapidly over the first 12-48 hours in the
      intensive care unit (ICU). These hormones have a direct physiological impact on
      insulin sensitivity (SI). Understanding the variability of SI is important for
      safely managing glycaemic levels and understanding the evolution of patient
      condition. The objective of this study is to assess the evolution of SI over the
      first two days of ICU stay, and using this data, propose a separate stochastic
      model to reduce the impact of SI variability during glycaemic control using the
      STAR glycaemic control protocol. METHODS: The value of SI was identified hourly
      for each patient using a validated physiological model. Variability of SI was
      then calculated as the hour-to-hour percentage change in SI. SI was examined
      using 6 hour blocks of SI to display trends while mitigating the effects of
      noise. To reduce the impact of SI variability on achieving glycaemic control a
      new stochastic model for the most variable period, 0-18 hours, was generated.
      Virtual simulations were conducted using an existing glycaemic control protocol
      (STAR) to investigate the clinical impact of using this separate stochastic model
      during this period of increased metabolic variability. RESULTS: For the first 18
      hours, over 80% of all SI values were less than 0.5 * 10(-3) L/mU x min, compared
      to 65% for >18 hours. Using the new stochastic model for the first 18 hours of
      ICU stay reduced the number of hypoglycaemic measurements during virtual trials.
      For time spent below 4.4, 4.0, and 3.0 mmol/L absolute reductions of 1.1%, 0.8%
      and 0.1% were achieved, respectively. No severe hypoglycaemic events (BG < 2.2
      mmol/L) occurred for either case. CONCLUSIONS: SI levels increase significantly,
      while variability decreases during the first 18 hours of a patients stay in ICU.
      Virtual trials, using a separate stochastic model for this period, demonstrated a
      reduction in variability and hypoglycaemia during the first 18 hours without
      adversely affecting the overall level of control. Thus, use of multiple models
      can reduce the impact of SI variability during model-based glycaemic control.

PMID- 24739336
TI  - Interaction between chaperone and protease functions of LON2, and autophagy
      during the functional transition of peroxisomes.
AB  - Functional transition of glyoxysomes to leaf peroxisomes is observed in greening
      cotyledons. Glyoxysomal proteins are rapidly degraded and leaf-peroxisomal
      proteins are transported into peroxisomes after cotyledons are exposed to light,
      but the molecular mechanisms underlying these processes remain unclear. We
      recently discovered that two degradation pathways are involved in the functional
      transition of peroxisomes using Arabidopsis thaliana. Lon protease 2 (LON2) is
      responsible for the degradation of glyoxysomal proteins inside peroxisomes, and,
      in parallel, autophagy eliminates damaged or obsolete peroxisomes. A double
      mutant defective in both the LON2- and autophagy-dependent degradation pathways
      accumulated glyoxysomal proteins after the cotyledons became green. Our study
      also demonstrated that the LON2- and autophagy-dependent pathways are
      interdependent, with the chaperone function of LON2 suppressing autophagic
      peroxisome degradation. Moreover, the peptidase domain of LON2 interferes with
      the suppression of autophagy, indicating that autophagy is regulated by
      intramolecular modulation between the proteolysis and chaperone functions of
      LON2. 

PMID- 24739334
TI  - Monitoring population and environmental parameters of invasive mosquito species
      in Europe.
AB  - To enable a better understanding of the overwhelming alterations in the invasive
      mosquito species (IMS), methodical insight into the population and environmental
      factors that govern the IMS and pathogen adaptations are essential. There are
      numerous ways of estimating mosquito populations, and usually these describe
      developmental and life-history parameters. The key population parameters that
      should be considered during the surveillance of invasive mosquito species are:
      (1) population size and dynamics during the season, (2) longevity, (3) biting
      behaviour, and (4) dispersal capacity. Knowledge of these parameters coupled with
      vector competence may help to determine the vectorial capacity of IMS and basic
      disease reproduction number (R0) to support mosquito borne disease (MBD) risk
      assessment. Similarly, environmental factors include availability and type of
      larval breeding containers, climate change, environmental change, human
      population density, increased human travel and goods transport, changes in
      living, agricultural and farming habits (e.g. land use), and reduction of
      resources in the life cycle of mosquitoes by interventions (e.g. source reduction
      of aquatic habitats). Human population distributions, urbanisation, and human
      population movement are the key behavioural factors in most IMS-transmitted
      diseases. Anthropogenic issues are related to the global spread of MBD such as
      the introduction, reintroduction, circulation of IMS and increased exposure to
      humans from infected mosquito bites. This review addresses the population and
      environmental factors underlying the growing changes in IMS populations in Europe
      and confers the parameters selected by criteria of their applicability. In
      addition, overview of the commonly used and newly developed tools for their
      monitoring is provided. 

PMID- 24739337
TI  - Paired oxygen isotope records reveal modern North American atmospheric dynamics
      during the Holocene.
AB  - The Pacific North American (PNA) teleconnection has a strong influence on North
      American climate. Instrumental records and century-scale reconstructions indicate
      an accelerating tendency towards the positive PNA state since the mid-1850s, but
      much less is known about long-term PNA variability. Here we reconstruct PNA-like
      climate variability during the mid- and late Holocene using paired oxygen isotope
      records from two regions in North America with robust, anticorrelated isotopic
      response to the modern PNA. We identify mean states of more negative and positive
      PNA-like climate during the mid- and late Holocene, respectively. Superimposed on
      the secular change between states is a robust, quasi-200-year oscillation, which
      we associate with the de Vries solar cycle. These findings suggest the
      persistence of PNA-like climate variability throughout the mid- and late
      Holocene, provide evidence for modulation of PNA over multiple timescales and may
      help researchers de-convolve PNA pattern variation from other factors reflected
      in palaeorecords. 

PMID- 24739338
TI  - School travel mode, parenting practices and physical activity among UK Year 5 and
      6 children.
AB  - BACKGROUND: School travel mode and parenting practices have been associated with
      children's physical activity (PA). The current study sought to examine whether PA
      parenting practices differ by school travel mode and whether school travel mode
      and PA parenting practices are associated with PA. METHODS: 469 children (aged 9
      11) wore accelerometers from which mean weekday and after-school (3.30 to 8.30
      pm) minutes of moderate-to-vigorous intensity PA (MVPA) and counts per minute
      (CPM) were derived. Mode of travel to and from school (passive vs. active) and PA
      parenting practices (maternal and paternal logistic support and modelling
      behaviour) were child-reported. RESULTS: Children engaged in an average of 59.7
      minutes of MVPA per weekday. Active travel to school by girls was associated with
      5.9 more minutes of MVPA per day compared with those who travelled to school
      passively (p = 0.004). After-school CPM and MVPA did not differ by school travel
      mode. There was no evidence that physical activity parenting practices were
      associated with school travel mode. CONCLUSIONS: For girls, encouraging active
      travel to school is likely to be important for overall PA. Further formative
      research may be warranted to understand how both parental logistic support and
      active travel decisions are operationalized in families as a means of
      understanding how to promote increased PA among pre-adolescent children.

PMID- 24739339
TI  - Coccidioidomycosis among cast and crew members at an outdoor television filming
      event--California, 2012.
AB  - In March 2013, the California Department of Public Health (CDPH) identified two
      Doctor's First Reports of Occupational Injury or Illness (DFRs) regarding Los
      Angeles County residents who had worked at the same jobsite in January 2012 and
      had been evaluated for possible work-associated coccidioidomycosis (valley
      fever). Occupational exposure to Coccidioides, the causative fungi, typically is
      associated with soil-disrupting activities. The physicians noted that both
      workers were cast or crew members filming a television series episode, and the
      site of possible exposure was an outdoor set in Ventura County, California. On
      the basis of their job titles, neither would have been expected to have been
      engaged in soil-disrupting activities. Los Angeles County Department of Public
      Health (LACDPH) conducted an outbreak investigation by using CDPH-provided
      occupational surveillance records, traditional infectious disease surveillance,
      and social media searches. This report describes the results of that
      investigation, which identified a total of five laboratory-confirmed and five
      probable cases linked to this filming event. The employer and site manager were
      interviewed. The site manager stated that they would no longer allow soil
      disruptive work at the site and would incorporate information about the potential
      risk for Coccidioides exposure onsite into work contracts. Public health
      professionals, clinicians, and the television and film industry should be aware
      that employees working outdoors in areas where Coccidioides is endemic (e.g.,
      central and southern California), even those not engaged in soil-disruptive work,
      might be at risk for coccidioidomycosis. 

PMID- 24739340
TI  - Assessment of blood lead levels among children aged <= 5 years--Zamfara State,
      Nigeria, June-July 2012.
AB  - Since 2010, Nigerian state and federal governments and the international
      community have been responding to an outbreak of lead poisoning caused by the
      processing of lead-containing gold ore in Zamfara State, Nigeria, that resulted
      in the deaths of approximately 400 children aged <= 5 years. Widespread
      education, surveys of high-risk villages, testing of blood lead levels (BLLs),
      medical treatment, and environmental cleanup all have been implemented. To
      evaluate the success of these remediation efforts in reducing the prevalence of
      lead poisoning and dangerous work practices, a population-based assessment of
      children's BLLs and ore processing techniques was conducted during June-July
      2012. The assessment found few children in need of medical treatment,
      significantly lower BLLs, and substantially less exposure of children to
      dangerous work practices. Public health strategies designed to identify and treat
      children with lead poisoning, clean up existing environmental hazards, and
      prevent children from being exposed to dangerous ore processing techniques can
      produce a sustained reduction in BLLs.

PMID- 24739341
TI  - Incidence and trends of infection with pathogens transmitted commonly through
      food--Foodborne Diseases Active Surveillance Network, 10 U.S. sites, 2006-2013.
AB  - Foodborne disease continues to be an important problem in the United States. Most
      illnesses are preventable. To evaluate progress toward prevention, the Foodborne
      Diseases Active Surveillance Network (FoodNet) monitors the incidence of
      laboratory-confirmed infections caused by nine pathogens transmitted commonly
      through food in 10 U.S. sites, covering approximately 15% of the U.S. population.
      This report summarizes preliminary 2013 data and describes trends since 2006. In
      2013, a total of 19,056 infections, 4,200 hospitalizations, and 80 deaths were
      reported. For most infections, incidence was well above national Healthy People
      2020 incidence targets and highest among children aged <5 years. Compared with
      2010-2012, the estimated incidence of infection in 2013 was lower for Salmonella,
      higher for Vibrio, and unchanged overall.? Since 2006-2008, the overall incidence
      has not changed significantly. More needs to be done. Reducing these infections
      requires actions targeted to sources and pathogens, such as continued use of
      Salmonella poultry performance standards and actions mandated by the Food Safety
      Modernization Act (FSMA). FoodNet provides federal and state public health and
      regulatory agencies as well as the food industry with important information
      needed to determine if regulations, guidelines, and safety practices applied
      across the farm-to-table continuum are working. 

PMID- 24739342
TI  - Concerns regarding a new culture method for Borrelia burgdorferi not approved for
      the diagnosis of Lyme disease.
AB  - In 2005, CDC and the Food and Drug Administration (FDA) issued a warning
      regarding the use of Lyme disease tests whose accuracy and clinical usefulness
      have not been adequately established. Often these are laboratory-developed tests
      (also known as "home brew" tests) that are manufactured and used within a single
      laboratory and have not been cleared or approved by FDA. Recently, CDC has
      received inquiries regarding a laboratory-developed test that uses a novel
      culture method to identify Borrelia burgdorferi, the spirochete that causes Lyme
      disease. Patient specimens reportedly are incubated using a two-step pre
      enrichment process, followed by immunostaining with or without polymerase chain
      reaction (PCR) analysis. Specimens that test positive by immunostaining or PCR
      are deemed "culture positive". Published methods and results for this laboratory
      developed test have been reviewed by CDC. The review raised serious concerns
      about false-positive results caused by laboratory contamination and the potential
      for misdiagnosis. 

PMID- 24739343
TI  - Assessment of potential zoonotic disease exposure and illness related to an
      annual bat festival--Idanre, Nigeria.
AB  - Bats provide vital ecologic services that humans benefit from, such as seed
      dispersal and pest control, and are a food source for some human populations.
      However, bats also are reservoirs for a number of high-consequence zoonoses,
      including paramyxoviruses, filoviruses, and lyssaviruses. The variety of viruses
      that bats harbor might be related to their evolutionary diversity, ability to fly
      large distances, long lifespans, and gregarious roosting behaviors. Every year a
      festival takes place in Idanre, Nigeria, in which males of all ages enter
      designated caves to capture bats; persons are forbidden from entering the caves
      outside of these festivities. Festival participants use a variety of techniques
      to capture bats, but protective equipment rarely is used, placing hunters at risk
      for bat scratches and bites. Many captured bats are prepared as food, but some
      are transported to markets in other parts of the country for sale as bushmeat.
      Bats also are presented to dignitaries in elaborate rituals. The health
      consequences of contact with these bats are unknown, but a number of viruses have
      been previously identified among Nigerian bats, including lyssaviruses,
      pegiviruses, and coronaviruses. Furthermore, the caves are home to Rousettus
      aegyptiacus bats, which are reservoirs for Marburg virus in other parts of
      Africa. 

PMID- 24739344
TI  - Increase in Vibrio parahaemolyticus infections associated with consumption of
      Atlantic Coast shellfish--2013.
AB  - Vibrio parahaemolyticus (Vp) is found naturally in coastal saltwater. In the
      United States, Vp causes an estimated 35,000 domestically acquired foodborne
      infections annually, of which most are attributable to consumption of raw or
      undercooked shellfish. Illness typically consists of mild to moderate
      gastroenteritis, although severe infection can occur. Demographic, clinical, and
      exposure information (including traceback information on implicated seafood) for
      all laboratory-confirmed illnesses are reported by state health departments to
      CDC through the Cholera and Other Vibrio Surveillance system. Vp isolates are
      distinguished by serotyping (>90 serotypes have been described) and by pulsed
      field gel electrophoresis (PFGE). 

PMID- 24739345
TI  - Mucosal immunity in HIV infection: what can be done to restore gastrointestinal
      associated lymphoid tissue function?
AB  - PURPOSE OF REVIEW: This review describes the impact of HIV infection on gut
      associated lymphoid tissue, the mechanisms for persistent gut-associated lymphoid
      tissue dysfunction despite effective antiretroviral therapy, and potential
      strategies to restore gut-associated lymphoid tissue function and promote immune
      reconstitution. RECENT FINDINGS: Recent studies indicate that unresolved
      microbial translocation and intestinal dysbiosis may continue to promote
      enteropathy as well as HIV-associated and non-HIV-associated conditions in many
      HIV patients who otherwise maintain therapeutic control of systemic viral
      replication. SUMMARY: Several novel therapeutic approaches to reduce intestinal
      inflammation and mitigate microbial translocation may hold promise for restoring
      gastrointestinal health and thereby increasing the efficacy of immune
      reconstitution in HIV-infected patients undergoing antiretroviral therapy.

PMID- 24739346
TI  - Detecting specific infections in children through host responses: a paradigm
      shift.
AB  - PURPOSE OF REVIEW: There is a need for improved diagnosis and for optimal
      classification of patients with infectious diseases. An alternative approach to
      the pathogen-detection strategy is based on a comprehensive analysis of the host
      response to the infection. This review focuses on the value of transcriptome
      analyses of blood leukocytes for the diagnosis and management of patients with
      infectious diseases. RECENT FINDINGS: Initial studies showed that RNA from blood
      leukocytes of children with acute viral and bacterial infections carried pathogen
      specific transcriptional signatures. Subsequently, transcriptional signatures for
      several other infections have been described and validated in humans with
      malaria, dengue, salmonella, melioidosis, respiratory syncytial virus, influenza,
      tuberculosis, and HIV. In addition, transcriptome analyses represent an
      invaluable tool to understand disease pathogenesis and to objectively classify
      patients according to the clinical severity. SUMMARY: Microarray studies have
      been shown to be highly reproducible using different platforms, and in different
      patient populations, confirming the value of blood transcriptome analyses to
      study pathogen-specific host immune responses in the clinical setting. Combining
      the detection of the pathogen with a comprehensive assessment of the host immune
      response will provide a new understanding of the correlations between specific
      causative agents, the host response, and the clinical manifestations of the
      disease.

PMID- 24739347
TI  - Possibilities to improve the genetic evaluation of a rare breed using limited
      genomic information and multivariate BLUP.
AB  - The use of molecular genetic information in the evaluation of livestock has
      become more common. This study looks at the efficacy of using such information to
      improve the genetic evaluation of a rare breed of dual-purpose cattle. Data were
      available in the form of pedigree information on the Gloucester cattle breed in
      the United Kingdom and recorded milk and beef performance on a small number of
      animals. In addition, molecular genetic information in the form of multi-marker,
      multiple regression results converted to a 1 to 10 score (Igenity scores) and 123
      single nucleotide polymorphism (SNP) genotypes for 199 non-recorded animals were
      available. Appropriate mixed-animal models were explored for the recorded traits
      and these were used to calculate estimated breeding values (EBV), and their
      accuracies, for 6527 animals in the breed's pedigree file. Various ways to
      improve the accuracy of these EBV were explored. This involved using multivariate
      BLUP analyses, genomic estimated breeding values (GEBV) and combining Igenity
      scores with recorded traits in a series of bivariate genetic analyses. Using the
      milk recording traits as an example, the accuracy of a number of traits could be
      improved using multivariate analyses by up to 14%, depending on the combination
      of traits used. The level of increase in accuracy largely corresponded to the
      absolute difference between the genetic and residual correlations between two
      traits, but this was not always symmetrical. The use of GEBV did not increase the
      accuracy of milk trait EBV owing to the low proportion of variance explained by
      the 101 SNPs used. Using Igenity scores in bivariate analyses with the recorded
      data was more successful in increasing EBV accuracy. The largest increases were
      found in genotyped animals with no recorded performance (e.g. a 58% increase in
      fat weight in milk); however, the size of the increase depended on the level of
      the genetic correlation between the recorded trait and the Igenity score for that
      trait. Lower levels of improvements in accuracy were seen in animals that were
      recoded but not genotyped, and ancestors which were neither genotyped nor
      recorded. This study demonstrated that it was possible to improve the accuracy of
      EBV estimation by including Igenity score information in genetic analyses but it
      also concluded that increasing the level of performance recording in the breed
      would be beneficial. 

PMID- 24739348
TI  - Risk factors associated with detailed reproductive phenotypes in dairy and beef
      cows.
AB  - The objective of this study was to identify detailed fertility traits in dairy
      and beef cattle from transrectal ultrasonography records and quantify the
      associated risk factors. Data were available on 148 947 ultrasound observations
      of the reproductive tract from 75 949 cows in 843 Irish dairy and beef herds
      between March 2008 and October 2012. Traits generated included (1) cycling at
      time of examination, (2) cystic structures, (3) early ovulation, (4) embryo death
      and (5) uterine score; the latter was measured on a scale of 1 (good) to 4 (poor)
      characterising the tone of the uterine wall and fluid present in the uterus.
      After editing, 72,773 records from 44,415 dairy and beef cows in 643 herds
      remained. Factors associated with the logit of the probability of a positive
      outcome for each of the binary fertility traits were determined using generalised
      estimating equations; linear mixed model analysis was used for the analysis of
      uterine score. The prevalence of cycling, cystic structures, early ovulation and
      embryo death was 84.75%, 3.87%, 7.47% and 3.84%, respectively. The occurrence of
      the uterine heath score of 1, 2, 3 and 4 was 70.63%, 19.75%, 8.36% and 1.26%,
      respectively. Cows in beef herds had a 0.51 odds (95% CI=0.41 to 0.63, P<0.001)
      of cycling at the time of examination compared with cows in dairy herds; stage of
      lactation at the time of examination was the same in both herd types.
      Furthermore, cows in dairy herds had an inferior uterine score (indicating poorer
      tone and a greater quantity of uterine fluid present) compared with cows in beef
      herds. The likelihood of cycling at the time of examination increased with parity
      and stage of lactation, but was reduced in cows that had experienced dystocia in
      the previous calving. The presence of cystic structures on the ovaries increased
      with parity and stage of lactation. The likelihood of embryo/foetal death
      increased with parity and stage of lactation. Dystocia was not associated with
      the presence of cystic structures or embryo death. Uterine score improved with
      parity and stage of lactation, while cows that experienced dystocia in the
      previous calving had an inferior uterine score. Heterosis was the only factor
      associated with increased likelihood of early ovulation. The fertility traits
      identified, and the associated risk factors, provide useful information on the
      reproductive status of dairy and beef cows.

PMID- 24739349
TI  - The impact of daily multiphase feeding on animal performance, body composition,
      nitrogen and phosphorus excretions, and feed costs in growing-finishing pigs.
AB  - The effect of feeding pigs in a three-phase feeding (3PF) system or a daily-phase
      feeding (DPF) system on growth performance, body composition, and N and P
      excretions was studied on 8 pens of 10 pigs each. Feeds for the 3PF and DPF
      treatments were obtained by mixing two feeds, one with a high nutrient
      concentration and the other with a low nutrient concentration. The DPF pigs
      tended (P=0.08) to consume more feed (+3.7%) than the 3PF pigs, but only during
      the first feeding phase. The DPF pigs consumed 7.3% less protein (P<0.01) but a
      similar amount of total P. For the whole growing period, the DPF pigs tended
      (P=0.08) to gain more weight (+2.4%) than the 3PF pigs, mainly because of faster
      growth (P=0.02) during the first feeding period. At the end of the experiment,
      total body protein mass was similar in the two treatment groups, but the DPF pigs
      had 8% more body lipids (P=0.04) than the 3PF pigs. Daily multiphase feeding
      reduced N excretion by 12% (P<0.01) but did not significantly reduce P excretion.
      In addition, feed costs, nutrient intake and nutrient excretion under the two
      feeding strategies were simulated and compared after different approaches were
      used to formulate complete feeds for each phase of the 3PF system, as well as the
      two feeds used in the DPF program. Simulated feed intake and growth was similar
      to those observed in the animal experiment. In comparison with the simulated 3PF
      system, the feed cost for the DPF pigs was reduced by 1.0%, the simulated N and P
      intakes were reduced by 7.3% and 4.4%, respectively, and the expected N and P
      excretions were reduced by 12.6% and 6.6%, respectively. The concomitant
      adjustment of the dietary concentration of nutrients to match the evaluated
      requirements of pig populations can be an efficient approach to significantly
      reduce feeding costs and N and P excretions in pig production systems. 

PMID- 24739350
TI  - Administration of a novel plant extract product via drinking water to post
      weaning piglets: effects on performance and gut health.
AB  - The present study evaluated the effects of a novel plant extract (PE) product
      (GrazixTM) on the performance and gut health of weaned piglets challenged with
      Escherichia coli. The PE was a standardised mixture of green tea leaves (Camellia
      sinensis) and pomegranate fruit (Punica granatum) obtained by using the
      LiveXtractTM process. A total of 144 piglets were weaned at 24 days and allocated
      to 8 for a 35-day experiment with a 2*2*2 factorial design comparing different
      treatments (water without product (CT) or 8 MUl/kg per day PE in drinking water
      (PE)), feeding regimens (ad libitum (AD) or restricted (RE)) and oral E. coli
      challenges on day 9 (sham (-) or infected (+)). There were six pens per group
      with three piglets per pen. On day 35, 24 of the RE feeding piglets were
      slaughtered. It was found that PE supplementation increased the average daily
      gain (ADG) from day 28 to day 35 (P=0.03) and increased the gain to feed ratio (G
      : F) from day 7 to day 14 (P=0.02). RE feeding led to lower feed intake in
      piglets during the 1st week (P<0.01), 2nd week (P=0.06), 3rd week (P=0.05), and
      throughout the course of the overall study period (P=0.05). E. coli challenge
      decreased the ADG and G : F ratio from day 7 to day 14 (P=0.08 and <0.01,
      respectively) and increased the faecal score (higher values indicate more severe
      diarrhoea) on days 14, 21, 28 and 35 (P<0.01). PE supplementation decreased the
      faecal score in the challenged piglets during the 1st week post-challenge
      (P<0.01). E. coli challenge increased the faecal E. coli level on day 14 (P=0.03)
      and increased the Enterobacteriaceae level on day 35 (P<0.01). Reduced faecal E.
      coli was observed on days 14 and 35 (P=0.05 and 0.02, respectively), and reduced
      Enterobacteriaceae (P<0.01) was found on day 35 in the PE animals. RE feeding
      increased the faecal Lactobacillus, Enterobacteriaceae and E. coli levels on day
      35 (P=0.02, <0.01 and <0.01, respectively). These results suggest that PE
      supplementation may improve the gut health status of post-weaning piglets and
      counteract some of the negative effects that occur when piglets are challenged
      with E. coli.

PMID- 24739351
TI  - Influence of estrus on dry matter intake, water intake and BW of dairy cows.
AB  - The objectives of this study were to analyze whether dry matter intake (DMI),
      water intake (WI) and BW were influenced by estrus. A second objective was to
      determine whether correlations exist among these traits in non-estrous days. Data
      collection included 34 Holstein-Friesian cows from the research farm 'Haus
      Riswick' of the Agricultural Chamber North Rhine-Westphalia, Germany. On an
      individual basis, daily DMI and daily WI were measured automatically by a scale
      in the feeding trough and a WI monitoring system, respectively. BW was determined
      by a walk-through scale fitted with two gates - one in front and one behind the
      scale floor. Data were analyzed around cow's estrus with day 0 (the day of
      artificial insemination leading to conception). Means during the reference
      period, defined as days -3 to -1 and 1 to 3, were compared with the means during
      estrus (day 0). DMI, WI and BW were affected by estrus. Of all cows, 85.3% and
      66.7% had reduced DMI and WI, respectively, on day 0 compared with the reference
      period. Lower BW was detected in 69.2% of all cows relative to the reference
      period. During the reference period, average DMI, WI and BW were 23.0, 86.6 and
      654.8 kg. A minimum DMI of 20.4 kg and a minimum BW of 644.2 kg were detected on
      the day of estrus, whereas the minimum WI occurred on the day before estrus.
      After estrus, DMI, WI and BW returned to baseline values. Intake of concentrated
      feed did not seem to be influenced by estrus. Positive correlations existed
      between daily DMI and daily WI (r=0.63) as well as between cows' daily BW and
      daily WI (r=0.23). The results warrant further investigations to determine
      whether monitoring of DMI, WI and BW may assist in predicting estrus. 

PMID- 24739352
TI  - Differential expression of cyclin G2, cyclin-dependent kinase inhibitor 2C and
      peripheral myelin protein 22 genes during adipogenesis.
AB  - Increase of fat cells (FCs) in adipose tissue is attributed to proliferation of
      preadipocytes or immature adipocytes in the early stage, as well as adipogenic
      differentiation in the later stage of adipose development. Although both events
      are involved in the FC increase, they are contrary to each other, because the
      former requires cell cycle activity, whereas the latter requires cell cycle
      withdrawal. Therefore, appropriate regulation of cell cycle inhibition is
      critical to adipogenesis. In order to explore the important cell cycle inhibitors
      and study their expression in adipogenesis, we adopted a strategy combining the
      Gene Expression Omnibus (GEO) database available on the NCBI website and the
      results of quantitative real-time PCR (qPCR) data in porcine adipose tissue.
      Three cell cycle inhibitors - cyclin G2 (CCNG2), cyclin-dependent kinase
      inhibitor 2C (CDKN2C) and peripheral myelin protein (PMP22) - were selected for
      study because they are relatively highly expressed in adipose tissue compared
      with muscle, heart, lung, liver and kidney in humans and mice based on two GEO
      DataSets (GDS596 and GDS3142). In the latter analysis, they were found to be more
      highly expressed in differentiating/ed preadipocytes than in undifferentiated
      preadipocytes in human and mice as shown respectively by GDS2366 and GDS2743. In
      addition, GDS2659 also suggested increasing expression of the three cell cycle
      inhibitors during differentiation of 3T3-L1 cells. Further study with qPCR in
      Landrace pigs did not confirm the high expression of these genes in adipose
      tissue compared with other tissues in market-age pigs, but confirmed higher
      expression of these genes in FCs than in the stromal vascular fraction, as well
      as increasing expression of these genes during in vitro adipogenic
      differentiation and in vivo development of adipose tissue. Moreover, the
      relatively high expression of CCNG2 in adipose tissue of market-age pigs and
      increasing expression during development of adipose tissue was also confirmed at
      the protein level by western blot analysis. Based on the analysis of the GEO
      DataSets and results of qPCR and Western blotting we conclude that all three cell
      cycle inhibitors may inhibit adipocyte proliferation, but promote adipocyte
      differentiation and hold a differentiated state by inducing and maintaining cell
      cycle inhibition. Therefore, their expression in adipose tissue is positively
      correlated with age and mature FC number. By regulating the expression of these
      genes, we may be able to control FC number, and, thus, reduce excessive fat
      tissue in animals and humans. 

PMID- 24739353
TI  - A study on some welfare-related parameters of hDAF transgenic pigs when compared
      with their conventional close relatives.
AB  - Pigs are increasingly used in medical research as transgenic laboratory animals;
      however, little knowledge is presently available concerning their welfare
      assessment. The aim of the present study was to investigate some welfare-related
      parameters of transgenic pigs intended for xenotrasplantation (human decay
      accelerating factor (hDAF)) when compared with their conventional (i.e. not
      transgenic) close relatives (full sibs and half sibs). A total of 14 Large White
      female transgenic pigs and 10 female non-transgenic (conventional) pigs from four
      litters were used. All pigs were from the same conventional boar, donor of the
      semen treated for sperm-mediated gene transfer. During the experiment, BW ranged
      from 50 to about 80 kg and pigs were weighed at the beginning and at the end of
      the experiment. Animals were subjected to a set of behavioural tests: a human
      approach test (HAT), a novel object test (NOT) and an open-door test (ODT). Food
      preferences were tested through the offer of different foods (banana, apple,
      carrot, cracker and lemon). During a 4-day period, pigs were diurnally videotaped
      to study the prevalence of the different behaviours and social interactions
      (aggressive and non-aggressive interactions). At the end of the trial, cortisol
      level had been assessed on bristles. No significant differences (P>0.05) were
      observed between hDAF transgenic and conventional pigs with respect to growth
      traits, reactivity towards unexpected situations (HAT, NOT, ODT), food
      preferences, main behavioural traits, social interactions and hair cortisol. 

PMID- 24739354
TI  - Application of the Welfare Quality(r) assessment system on European beef bull
      farms.
AB  - Welfare concerns for intensive beef production have often been raised, but on
      farm welfare assessment studies are rare. The aim of this study was to apply the
      Welfare Quality(r) (WQ) welfare assessment system for fattening cattle on beef
      bull farms to evaluate the state of welfare at the level of WQ measures and of
      aggregated scores, as well as overall classification. In addition, the purpose
      was to evaluate two ways of providing feedback information to the farmers with
      regard to possible welfare improvements on the farms. The study was conducted in
      Austria, Germany and Italy on a total of 63 beef bull farms with deep litter or
      cubicle-housing systems. Assessments were carried out 3 times (1 month and 7
      months apart from the initial visit). In every country, farmers were assigned to
      two treatment groups (feedback from initial visit as written report, F, written
      feedback plus oral advice, FA) and a control group (C), which did not receive any
      feedback. At the criterion level, the highest average welfare scores were
      obtained from 'Absence of prolonged hunger' (94/100 points) followed by 'Absence
      of pain induced by management procedures' (88/100) and 'Comfort around resting'
      (77/100). Most welfare concerns related to the criteria 'Absence of disease'
      (40/100), 'Expression of social behaviour' (44/100) and 'Positive emotional
      state' (48/100), thus indicating room for improvements. Two-thirds of the farms
      achieved the 'Enhanced' level, about one-third was judged 'Acceptable' and only
      one farm 'Excellent'. After 6 months of monitoring period, there was no
      significant welfare improvement in both the treatment groups as compared with the
      control group. Reasons for the lack of effect may mainly be seen in the short
      monitoring period and a lack of external incentives. In conclusion, the WQ
      assessment system revealed areas for improvement, but longer term studies and
      investigations on alternative ways of transferring outcomes from on-farm welfare
      assessments to farmers should be carried out in future. 

PMID- 24739355
TI  - Effects of neonatal surgical castration and immunocastration in male pigs on
      blood T lymphocytes and health markers.
AB  - Surgical castration in pig husbandry is criticized for welfare reasons. Thus, it
      is necessary to evaluate alternative ways of rearing male pigs, such as entire or
      immunocastrated animals. Immunocastration is a vaccination directed against
      gonadotropin-releasing hormone (GnRH) to suppress the production of sexual
      hormones. This study aimed at investigating the effects of these two methods of
      castration in comparison with intact male pigs on blood T-lymphocyte subsets and
      function, the immunoglobulin (Ig) response to an influenza vaccine and health
      markers during sexual development. A total of 70 animals were allocated to three
      experimental groups: entire (E), surgically castrated at 5 to 6 days of age (SC),
      and immunized against GnRH at 3 and 4 months of age (IC). Blood samples were
      collected at 3, 4 and 5 months. At slaughter, global health status and body and
      spleen weights were measured. Results showed that SC male pigs had fewer blood
      lymphocytes than E pigs at 4 and 5 months (P<0.05), whereas IC pigs did not
      differ significantly from E pigs. The percentages of CD3+, CD3+CD4+ and CD3+CD8+
      lymphocytes were not altered by treatment (P>0.1). Compared with E pigs, the SC
      pigs had a higher percentage of CD3+CD4+CD8+ cells at 4 months, whereas the IC
      pigs had a higher percentage at 5 months (P<0.05). Regarding gammadeltaT cells,
      SC pigs had a lower percentage than E pigs at 4 and 5 months (P<0.05), whereas IC
      pigs did not differ significantly from E pigs at any age. However, there were no
      consequences on T-lymphocyte proliferation and total IgG or anti-influenza Ig. At
      slaughter, relative spleen weight was decreased in IC pigs, whereas pneumonia
      score was decreased in SC pigs relatively to E pigs. Overall, no clear functional
      consequences of either method on commercial pig immune abilities were
      demonstrated, but more investigations are required to ascertain this conclusion. 

PMID- 24739356
TI  - Relationship between abstract thinking and eye gaze pattern in patients with
      schizophrenia.
AB  - BACKGROUND: Effective integration of visual information is necessary to utilize
      abstract thinking, but patients with schizophrenia have slow eye movement and
      usually explore limited visual information. This study examines the relationship
      between abstract thinking ability and the pattern of eye gaze in patients with
      schizophrenia using a novel theme identification task. METHODS: Twenty patients
      with schizophrenia and 22 healthy controls completed the theme identification
      task, in which subjects selected which word, out of a set of provided words, best
      described the theme of a picture. Eye gaze while performing the task was recorded
      by the eye tracker. RESULTS: Patients exhibited a significantly lower correct
      rate for theme identification and lesser fixation and saccade counts than
      controls. The correct rate was significantly correlated with the fixation count
      in patients, but not in controls. CONCLUSIONS: Patients with schizophrenia showed
      impaired abstract thinking and decreased quality of gaze, which were positively
      associated with each other. Theme identification and eye gaze appear to be useful
      as tools for the objective measurement of abstract thinking in patients with
      schizophrenia.

PMID- 24739358
TI  - Delta-opioid receptor blockade in the ventral pallidum increases perceived
      palatability and consumption of saccharin solution in rats.
AB  - The ventral pallidum (VP) is involved in ingestive behaviour. It receives dense
      GABAergic projections from the nucleus accumbens. GABAergic terminals in the VP
      co-express enkephalin, an endogenous ligand of delta-opioid receptors. The role
      of the delta-opioid receptors in the VP in the context of ingestive behaviour
      remains unclear, in contrast to the well-understood involvement of the mu-opioid
      receptors. We used the single-bottle test to examine the effects of VP
      microinjections of the delta-opioid receptor antagonist naltrindole on
      consumption of a saccharin solution. Naltrindole injections significantly
      increased the intake of saccharin, but not water, during a 2-h test session. We
      also investigated perceived palatability of saccharin using a taste reactivity
      test. The drug treatments increased ingestive responses to intraorally infused
      saccharin. Further experimentation explored the role of VP delta-opioid receptors
      in behavioural responses to saccharin that were previously paired with malaise
      upon the retrieval of conditioned taste aversion (CTA). Naltrindole-injected rats
      exhibited longer latency for the first occurrence of aversive responses than
      vehicle-injected control rats. However, there was no between-group difference in
      total aversive responses. These results suggest that naltrindole injections into
      the VP induce an enhancement of perceived palatability of a normally preferred
      saccharin solution, and thereby facilitate consumption of the solution. On the
      other hand, delayed aversive responses to the conditioned aversive saccharin
      suggest that the delta-opioid receptors in the VP mediate the initiation of
      aversive taste reactivity responses to the conditioned stimulus upon CTA
      retrieval. 

PMID- 24739357
TI  - Identification of species in the angiosperm family Apiaceae using DNA barcodes.
AB  - Apiaceae (Umbelliferae) is a large angiosperm family that includes many
      medicinally important species. The ability to identify these species and their
      adulterants is important, yet difficult to do so because of their subtle fruit
      morphological differences and often lack of diagnostic features in preserved
      specimens. Moreover, dried roots are often the official medical organs, making
      visual identification to species almost impossible. DNA barcoding has been
      proposed as a powerful taxonomic tool for species identification. The Consortium
      for the Barcode of Life (CBOL) Plant Working Group has recommended the
      combination of rbcL+matK as the core plant barcode. Recently, the China Plant BOL
      Group proposed that the nuclear ribosomal DNA internal transcribed spacer (ITS),
      as well as a subset of this marker (ITS2), be incorporated alongside rbcL+matK
      into the core barcode for seed plants, particularly angiosperms. In this study,
      we assess the effectiveness of these four markers plus psbA-trnH as Apiaceae
      barcodes. A total of 6032 sequences representing 1957 species in 385 diverse
      genera were sampled, of which 211 sequences from 50 individuals (representing
      seven species) were newly obtained. Of these five markers, ITS and ITS2 showed
      superior results in intra- and interspecific divergence and DNA barcoding gap
      assessments. For the matched data set (173 samples representing 45 species in
      five genera), the ITS locus had the highest identification efficiency (73.3%),
      yet ITS2 also performed relatively well with 66.7% identification efficiency. The
      identification efficiency increased to 82.2% when using an ITS+psbA-trnH marker
      combination (ITS2+psbA-trnH was 80%), which was significantly higher than that of
      rbcL+matK (40%). For the full sample data set (3052 ITS sequences, 3732 ITS2
      sequences, 1011 psbA-trnH sequences, 567 matK sequences and 566 rbcL sequences),
      ITS, ITS2, psbA-trnH, matK and rbcL had 70.0%, 64.3%, 49.5%, 38.6% and 32.1%
      discrimination abilities, respectively. These results confirm that ITS or its
      subset ITS2 be incorporated into the core barcode for Apiaceae and that the
      combination of ITS/ITS2+psbA-trnH has much potential value as a powerful,
      standard DNA barcode for Apiaceae identification.

PMID- 24739359
TI  - Involvement of the nucleus accumbens shell glutamatergic system in ACPA-induced
      impairment of inhibitory avoidance memory consolidation.
AB  - Interactions between cannabinoid and glutamate systems have been demonstrated in
      some brain areas associated with mnemonic functions. This study investigates the
      effects of bilateral post-training intra-nucleus accumbens (NAc) shell
      administrations of glutamate NMDA receptor agents on memory impairment induced by
      cannabinoid CB1 receptor activation during a step-through inhibitory avoidance
      (IA) task. Our results showed post-training administration of ACPA (CB1 receptor
      agonist; 3 ng/side) impairs IA memory consolidation, whereas AM251 (CB1 receptor
      antagonist; 0.3, 3 and 30 ng/side), NMDA (0.3, 3 and 30 ng/side), and d-AP7 (NMDA
      receptor antagonist; 3, 30 and 300 ng/side) were ineffective. However, co
      administration of AM251 (30 ng/side) or NMDA (30 ng/side) with ACPA (3 ng/side)
      prevented the memory-impairing effect of ACPA. Meanwhile, co-administration of
      NMDA (30 ng/side) and a subthreshold dose of ACPA (0.15 ng/side) decreased memory
      consolidation. Moreover, post-training microinjection of AM251 (30 ng/side) or d
      AP7 (300 ng/side) prevented memory impairment induced by co-administration of
      subthreshold doses of NMDA and ACPA. The data indicated that NMDA receptor
      mechanism(s), at least partly, play(s) a role in modulating the effect of ACPA on
      memory consolidation in the NAc shell.

PMID- 24739360
TI  - Effect of amplitude and duration of impulsive pressure on endothelial
      permeability in in vitro fluid percussion trauma.
AB  - BACKGROUND: Intracranial pressure changes during head impact cause brain injuries
      such as vasogenic edema and cerebral contusion. However, the influence of
      impulsive pressure on endothelial function has not yet been fully studied in
      vitro. In this study, we developed a pressure loading device that produced
      positive and negative pressures by modifying an in vitro fluid percussion model
      and examined the effects of the amplitude and duration of the pressures on
      endothelial permeability. METHODS: Human umbilical vein endothelial cells were
      subjected to three types of positive pressure (average amplitude/average duration
      of 352 kPa/23 ms, 73 kPa/27 ms, and 70 kPa/44 ms) and three types of negative
      pressure (-72 kPa/41 ms, -67 kPa/104 ms, and -91 kPa/108 ms), and the
      transendothelial electrical resistance (TEER) was measured between 15 min and 24
      h after pressure loading for quantifying the formation of an integral monolayer
      of endothelial cells. After loading, vascular endothelial- (VE-) cadherin, an
      endothelium-specific cell-cell adhesion molecule involved in endothelial barrier
      function, was stained and observed using fluorescence microscopy. RESULTS: The
      pressure loading device could produce positive pressure pulses with amplitudes of
      53-1348 kPa and durations of 9-29.1 ms and negative pressure pulses with
      amplitudes of -52 - -93 kPa and durations of 42.9-179.5 ms. The impulsive
      pressure reduced the TEER associated with the change in VE-cadherin localization.
      Additionally, TEER decreased considerably at 15 min and 6 h post-loading, with
      these changes being significant in positive pressure with larger amplitude and
      shorter duration and in all types of negative pressures compared to pre-loading.
      CONCLUSIONS: The changes in intracranial pressure during head impact impair
      endothelial barrier function by the disruption of the integrity of endothelial
      cell-cell junctions, and the degree of increase in endothelial permeability
      depends on the amplitude, duration, and direction (compressive and tensile) of
      the impulsive pressure.

PMID- 24739362
TI  - Targeting the affective component of chronic pain: a case series of deep brain
      stimulation of the anterior cingulate cortex.
AB  - BACKGROUND: Deep brain stimulation (DBS) has shown considerable promise for
      relieving nociceptive and neuropathic symptoms of refractory chronic pain.
      Nevertheless, for some patients, standard DBS for pain remains poorly
      efficacious. Pain is a multidimensional experience with an affective component:
      the unpleasantness. The anterior cingulate cortex (ACC) is a structure involved
      in this affective component, and targeting it may relieve patients' pain.
      OBJECTIVE: To describe the first case series of ACC DBS to relieve the affective
      component of chronic neuropathic pain. METHODS: Sixteen patients (13 male and 3
      female patients) with neuropathic pain underwent bilateral ACC DBS. The mean age
      at surgery was 48.7 years (range, 33-63 years). Patient-reported outcome measures
      were collected before and after surgery using a Visual Analog Scale, SF-36
      quality of life survey, McGill Pain Questionnaire, and EQ-5D (EQ-5D and EQ-5D
      Health State) questionnaires. RESULTS: Fifteen patients (93.3%) transitioned from
      externalized to fully internalized systems. Eleven patients had data to be
      analyzed with a mean follow-up of 13.2 months. Post-surgery, the Visual Analog
      Scale score dropped below 4 for 5 of the patients, with 1 patient free of pain.
      Highly significant improvement on the EQ-5D was observed (mean, +20.3%; range,
      +0%-+83%; P = .008). Moreover, statistically significant improvements were
      observed for the physical functioning and bodily pain domains of the SF-36
      quality-of-life survey: mean, +64.7% (range, -8.9%-+276%; P = .015) and mean
      +39.0% (range, -33.8%-+159%; P = .050), respectively. CONCLUSION: Affective ACC
      DBS can relieve chronic neuropathic pain refractory to pharmacotherapy and
      restore quality of life.

PMID- 24739361
TI  - ARACNe-based inference, using curated microarray data, of Arabidopsis thaliana
      root transcriptional regulatory networks.
AB  - BACKGROUND: Uncovering the complex transcriptional regulatory networks (TRNs)
      that underlie plant and animal development remains a challenge. However, a vast
      amount of data from public microarray experiments is available, which can be
      subject to inference algorithms in order to recover reliable TRN architectures.
      RESULTS: In this study we present a simple bioinformatics methodology that uses
      public, carefully curated microarray data and the mutual information algorithm
      ARACNe in order to obtain a database of transcriptional interactions. We used
      data from Arabidopsis thaliana root samples to show that the transcriptional
      regulatory networks derived from this database successfully recover previously
      identified root transcriptional modules and to propose new transcription factors
      for the SHORT ROOT/SCARECROW and PLETHORA pathways. We further show that these
      networks are a powerful tool to integrate and analyze high-throughput expression
      data, as exemplified by our analysis of a SHORT ROOT induction time-course
      microarray dataset, and are a reliable source for the prediction of novel root
      gene functions. In particular, we used our database to predict novel genes
      involved in root secondary cell-wall synthesis and identified the MADS-box TF
      XAL1/AGL12 as an unexpected participant in this process. CONCLUSIONS: This study
      demonstrates that network inference using carefully curated microarray data
      yields reliable TRN architectures. In contrast to previous efforts to obtain root
      TRNs, that have focused on particular functional modules or tissues, our root
      transcriptional interactions provide an overview of the transcriptional pathways
      present in Arabidopsis thaliana roots and will likely yield a plethora of novel
      hypotheses to be tested experimentally.

PMID- 24739363
TI  - Are aneurysms treated with balloon-assisted coiling and stent-assisted coiling
      different? Morphological analysis of 113 unruptured wide-necked aneurysms treated
      with adjunctive devices.
AB  - BACKGROUND: In the endovascular treatment of wide-necked unruptured aneurysms,
      there is controversy over which adjunctive device (stent vs balloon) is
      appropriate. At the payer level it has been posited that stents and balloons
      treat the same aneurysms, and, as such, the more expensive stents should not be
      reimbursed. OBJECTIVE: We challenge this assertion, and instead hypothesize that
      aneurysms treated with stent assistance are morphologically different than those
      selected for balloon assistance. METHODS: Retrospective review of unruptured
      aneurysms treated with an adjunctive device between 2008 and 2010. Morphological
      analysis was performed on the pretreatment 2-D catheter angiogram. The immediate
      posttreatment Raymond score was compared with that seen on the 12-month follow-up
      angiogram. RESULTS: One hundred six unruptured aneurysms were treated with an
      adjunctive device and followed for a mean of 24.5 months. Morphological analysis
      revealed a lower dome-to-neck ratio (1.5 vs 1.2) and aspect ratio (1.44 vs 1.16)
      in the aneurysms treated with stent assistance vs balloon assistance. Of the
      15.3% that were worse on follow-up angiography, there was no statistical
      difference between those treated with a stent vs a balloon (17.1% vs 14.2%). The
      overall re-treatment rate was 10.2% and was not statistically different between
      the 2 groups (12.7% vs 5.7%). CONCLUSION: We found that unruptured aneurysms
      selected for treatment with stent-assisted coiling are morphologically different
      from those selected for treatment with balloon assistance. Despite the more
      challenging morphology, Raymond scores and re-treatment rates at 1 year were not
      statistically different between the 2 groups, suggesting an important role for
      stents in the treatment of unruptured aneurysms.

PMID- 24739364
TI  - The upper limit of cerebral blood flow autoregulation is decreased with
      elevations in intracranial pressure.
AB  - BACKGROUND: The upper limit of cerebrovascular pressure autoregulation (ULA) is
      inadequately characterized. OBJECTIVE: To delineate the ULA in an infant swine
      model. METHODS: Neonatal piglets with sham surgery (n = 9), interventricular
      fluid infusion (INF) (n = 10), controlled cortical impact (CCI) (n = 10), or CCI
      + INF (n = 11) had intracranial pressure monitoring and bilateral cortical laser
      Doppler flowmetry recordings during arterial hypertension to lethality using an
      aortic balloon catheter. An increase of red cell flux as a function of cerebral
      perfusion pressure was determined by piecewise linear regression, and static
      rates of autoregulation were determined above and below this inflection. The ULA
      was rendered as the first instance of an upward deflection of Doppler flux
      causing a static rate of autoregulation decrease greater than 0.5. RESULTS: ULA
      was identified in 55% of piglets after sham surgery, 70% after INF, 70% after
      CCI, and 91% after CCI with INF (P = .36). When identified, the median
      (interquartile range) ULA was as follows: sham group, 102 mm Hg (97-109 mm Hg);
      INF group, 75 mm Hg (52-84 mm Hg); CCI group, 81 mm Hg (69-101 mm Hg); and CCI +
      INF group, 61 mm Hg (52-57 mm Hg) (P = .01). In post hoc analysis, both groups
      with interventricular INF had significantly lower ULA than that observed in the
      sham group. CONCLUSION: Neonatal piglets without intracranial pathology tolerated
      acute hypertension with minimal perturbation of cerebral blood flow. Piglets with
      acutely increased intracranial pressure with or without trauma demonstrated loss
      of autoregulation when subjected to arterial hypertension.

PMID- 24739365
TI  - En bloc resection of upper thoracic chordoma via a combined simultaneous
      anterolateral thoracoscopic and posterior approach.
AB  - BACKGROUND: En bloc resection of chordomas is associated with increased patient
      survival. Achievement of en bloc resection, however, may present a great surgical
      challenge, particularly in the mobile spine. Novel multidisciplinary techniques
      may enable en bloc resection of lesions presenting in anatomically challenging
      locations. A combined simultaneous thoracoscopic and posterior approach in a
      patient with an upper thoracic chordoma is presented; en bloc resection was
      achieved. OBJECTIVE: To show the feasibility, safety, and utility of performing a
      thoracoscopy-assisted en bloc resection of a chordoma involving the upper
      thoracic spine. METHODS: A case study is presented of a patient with biopsy
      proven chordoma of T2-3 with predominantly paravertebral involvement who
      underwent multilevel en bloc resection via a simultaneous combined anterolateral
      thoracoscopic and posterior approach. Thoracoscopic assistance achieved
      separation of the tumor and ventral spine from the adjacent mediastinal
      structures. En bloc resection proceeded without complication. The spine was
      stabilized with posterior instrumentation. RESULTS: A multilevel en bloc
      resection was achieved with negative margins, preserving more than half of the
      remaining vertebral bodies and allowing short segment posterior fixation without
      extension into the cervical spine. The patient remained neurologically intact.
      CONCLUSION: A combined simultaneous thoracoscopic and posterior approach is safe
      and effective for en bloc resection of multilevel chordoma involving the upper
      thoracic spine. This technique allows for a plane to be established ventrally
      between the tumor and the mediastinum, thus assisting with safe osteotomies via
      the posterior approach.

PMID- 24739366
TI  - MicroRNAs as biomarkers in pituitary tumors.
AB  - The use of extracellular microRNAs (miRNAs) as circulating biomarkers is
      currently leading to relevant advances in the diagnosis and assessment of
      prognosis of several diseases. Specific miRNAs have also been shown to play a
      role in the pathophysiology of many neoplastic and non-neoplastic diseases. A
      number of studies have demonstrated that miRNAs show differential expression in
      various tumors, such as in the prostate, ovary, lung, breast, brain, and
      pituitary. Recent findings have built connections between miRNAs that are
      deregulated within the tumor and their presence in peripheral blood. MiRNAs have
      been shown to be stable in the blood where they are present in either free and/or
      uncomplexed form, as well as packed in microvesicles, exosomes, and apoptotic
      bodies, or bound to different proteins. Because the pituitary is a highly
      vascularized organ that releases hormones into the circulation, miRNAs would be
      useful biomarkers for the diagnosis of pituitary tumors, as well as for
      predicting or detecting recurrence after surgery. Here we review the biological
      significance of miRNAs in pituitary tumors and the potential value of circulating
      miRNAs as biomarkers.

PMID- 24739367
TI  - French research infrastructures to develop and validate glioma biomarkers.

PMID- 24739368
TI  - In reply: French research infrastructures to develop and validate glioma
      biomarkers.

PMID- 24739369
TI  - Preliminary study on the relation between the coping patterns and mental health
      of radiation control personnel and nondestructive inspectors engaged in the
      periodic inspections of nuclear power plants.
AB  - OBJECTIVE: In order to safely manage nuclear power plants, their workforce should
      be mentally healthy. This study clarifies the coping strategies of radiation
      control personnel and nondestructive inspectors engaged in the periodic
      inspection of nuclear power plants, the effect of the coping strategies on their
      mental health, as well as any effect based on whether or not they had worked
      after the nuclear disaster caused by the Great East Japan Earthquake and tsunami
      in March 2011. METHODS: A questionnaire survey was administered to 133
      technicians attending a certification course, and among them, our subjects of
      analysis were 104 people with work experience in radiation control and/or
      nondestructive inspection. RESULTS: The results indicated that even among workers
      of the same company who were assigned to similar duties in the periodic
      inspections of nuclear power plants, the group that had worked at a nuclear plant
      after the disaster had a tendency to use coping strategies, such as giving up and
      avoidance-like thinking, which was dissimilar to the group that had not worked at
      a nuclear plant after the disaster. Further, the former group had higher levels
      of distress than those who tended to use other coping strategies. In addition,
      the results suggested that the plan-drafting strategy adopted by the group that
      had not worked after the disaster did not result in stress reduction. DISCUSSION:
      Based on these results, we propose a stress management program specifically for
      radiation workers.

PMID- 24739370
TI  - Allergic contact dermatitis from two-component acrylic resin in a manicurist and
      a dental hygienist.
AB  - BACKGROUNDS: Two-component acrylic resin used in nail art and dentistry can cause
      allergic contact dermatitis (ACD), but only a few reports from Japan have been
      published. CASES: A 35-year-old female manicurist (case 1) and 30-year-old female
      dental hygienist (case 2) were diagnosed with ACD caused by ethyl methacrylate
      and methyl methacrylate in a liquid monomer of two-component acrylic resin
      respectively. Case 1 was sensitized from direct skin contact with nail art
      acrylic products, which could have been avoided, and gave up both being a
      manicurist and a user. Onset in case 2 occurred when she started to work as an
      apprentice. She had believed that the cause of her symptoms was use of disposable
      natural rubber gloves, not a liquid monomer penetrating through her gloves, until
      she was patch tested positive to (meth)acrylates and liquid monomer. CONCLUSIONS:
      To prevent sensitization, it should be emphasized in occupational training in
      both specialties that there should be no direct contact with acrylic products and
      that disposable gloves do not have sufficient protecting properties.

PMID- 24739371
TI  - Development of cost estimation tools for total occupational safety and health
      activities and occupational health services: cost estimation from a corporate
      perspective.
AB  - OBJECTIVES: The aim of the present study was to develop standardized cost
      estimation tools that provide information to employers about occupational safety
      and health (OSH) activities for effective and efficient decision making in
      Japanese companies. METHODS: We interviewed OSH staff members including full-time
      professional occupational physicians to list all OSH activities. Using activity
      based costing, cost data were obtained from retrospective analyses of
      occupational safety and health costs over a 1-year period in three manufacturing
      workplaces and were obtained from retrospective analyses of occupational health
      services costs in four manufacturing workplaces. We verified the tools
      additionally in four workplaces including service businesses. RESULTS: We created
      the OSH and occupational health standardized cost estimation tools. OSH costs
      consisted of personnel costs, expenses, outsourcing costs and investments for 15
      OSH activities. The tools provided accurate, relevant information on OSH
      activities and occupational health services. CONCLUSIONS: The standardized
      information obtained from our OSH and occupational health cost estimation tools
      can be used to manage OSH costs, make comparisons of OSH costs between companies
      and organizations and help occupational health physicians and employers to
      determine the best course of action.

PMID- 24739372
TI  - Effort-reward imbalance and low back pain among eldercare workers in nursing
      homes: a cross-sectional study in Kagawa Prefecture, Japan.
AB  - OBJECTIVES: To clarify effort-reward imbalance among eldercare workers in nursing
      homes and to examine the association between the effort-reward imbalance (ERI)
      and low back pain (LBP) among them. METHODS: A total of 549 questionnaires were
      distributed to a random sample comprising 23% of the 79 special elderly nursing
      homes in Kagawa in 2013. A total of 467 eldercare workers (response rate 85%)
      participated in this study. Of the 467 eligible respondents, 372 (80%) completed
      all items of the ERI questionnaire. Complete data were available for 342 (73%)
      eldercare workers. RESULTS: Of the 342 respondents, 215 (63%) had LBP at the time
      of the study, and 291 (85%) showed a critical "high cost/low gain" condition as
      determined by an effort-reward ratio >1. Multiple logistic regression analyses
      adjusted for age, gender, previous LBP experience, high-risk work and K6 score
      showed that eldercare workers with a high ERI had a higher risk for LBP than
      workers with a low ERI (OR, 1.96; 95% CI, 1.02-3.77). CONCLUSIONS: Most eldercare
      workers have a high ERI, and their LBP is associated with their ERI. Balancing
      effort and reward may be an important factor for improving LBP among eldercare
      workers in nursing homes.

PMID- 24739373
TI  - Assessment of the genotoxicity of 1,2-dichloropropane and dichloromethane after
      individual and co-exposure by inhalation in mice.
AB  - OBJECTIVE: Occurrence of cholangiocarcinoma was recently reported at a high
      incidence rate among the employees working for an offset printing company in
      Osaka, Japan. 1,2-Dichloropropane (1,2-DCP) and dichloromethane (DCM) are
      suspected to be the causes of the cancer, as they had been used as ink cleaners
      in large amounts. However, it is not clear whether these chlorinated organic
      solvents played a role in the occurrence of cholangiocarcinoma or why the
      incidence rate is so high among the workers in this industry. To provide possible
      evidence for this severe occupational problem, we investigated the genotoxic
      effects of 1,2-DCP and DCM. METHODS: Male B6C3F1 and gpt Delta C57BL/6J mice were
      exposed by inhalation to the individual solvents or both solvents at multiple
      concentrations including the levels that were possibly present in the workplaces.
      The genotoxicity was analyzed by Pig-a gene mutation and micronuclei assays in
      peripheral blood and gpt mutation and comet assays in the livers of mice after
      repeated inhalation of 1,2-DCP or/and DCM. RESULTS: The Pig-a mutant frequencies
      and micronuclei incidences were not significantly increased by exposure of either
      1,2-DCP or/and DCM at any concentration, suggesting there was no genotoxic
      potential in bone marrow for both solvents. In the liver, DNA damage, as measured
      by the comet assay, was dose dependently increased by 1,2-DCP but not by DCM. The
      gpt mutant frequency was 2.6-fold that of the controls in the co-exposure group.
      CONCLUSIONS: These results indicate that 1,2-DCP showed stronger genotoxicity in
      the liver and that the genotoxic effects were greatly enhanced by simultaneous
      exposure to DCM.

PMID- 24739374
TI  - Mortality risk associated with underweight: a census-linked cohort of 31,578
      individuals with up to 32 years of follow-up.
AB  - BACKGROUND: In contrast to obesity, information on the health risks of
      underweight is sparse. We examined the long-term association between underweight
      and mortality by considering factors possibly influencing this relationship.
      METHODS: We included 31,578 individuals aged 25-74 years, who participated in
      population based health studies between 1977 and 1993 and were followed-up for
      survival until 2008 by record linkage with the Swiss National Cohort (SNC). Body
      Mass Index (BMI) was calculated from measured (53% of study population) or self
      reported height and weight. Underweight was defined as BMI < 18.5 kg/m2. Cox
      regression models were used to determine mortality Hazard Ratios (HR) of
      underweight vs. normal weight (BMI 18.5- < 25.0 kg/m2). Covariates were study,
      sex, smoking, healthy eating proxy, sports frequency, and educational level.
      RESULTS: Underweight individuals represented 3.0% of the total study population
      (n = 945), and were mostly women (89.9%). Compared to normal weight, underweight
      was associated with increased all-cause mortality (HR: 1.37; 95% CI: 1.14-1.65).
      Increased risk was apparent in both sexes, regardless of smoking status, and
      mainly driven by excess death from external causes (HR: 3.18; 1.96-5.17), but not
      cancer, cardiovascular or respiratory diseases. The HR were 1.16 (0.88-1.53) in
      studies with measured BMI and 1.59 (1.24-2.05) with self-reported BMI.
      CONCLUSIONS: The increased risk of dying of underweight people was mainly due to
      an increased mortality risk from external causes. Using self-reported BMI may
      lead to an overestimation of mortality risk associated with underweight.

PMID- 24739375
TI  - Dynamic regulation of genetic pathways and targets during aging in Caenorhabditis
      elegans.
AB  - Numerous genetic targets and some individual pathways associated with aging have
      been identified using the worm model. However, less is known about the genetic
      mechanisms of aging in genome wide, particularly at the level of multiple
      pathways as well as the regulatory networks during aging. Here, we employed the
      gene expression datasets of three time points during aging in Caenorhabditis
      elegans (C. elegans) and performed the approach of gene set enrichment analysis
      (GSEA) on each dataset between adjacent stages. As a result, multiple genetic
      pathways and targets were identified as significantly down- or up-regulated.
      Among them, 5 truly aging-dependent signaling pathways including MAPK signaling
      pathway, mTOR signaling pathway, Wnt signaling pathway, TGF-beta signaling
      pathway and ErbB signaling pathway as well as 12 significantly associated genes
      were identified with dynamic expression pattern during aging. On the other hand,
      the continued declines in the regulation of several metabolic pathways have been
      demonstrated to display age-related changes. Furthermore, the reconstructed
      regulatory networks based on three of aging related Chromatin immunoprecipitation
      experiments followed by sequencing (ChIP-seq) datasets and the expression
      matrices of 154 involved genes in above signaling pathways provide new insights
      into aging at the multiple pathways level. The combination of multiple genetic
      pathways and targets needs to be taken into consideration in future studies of
      aging, in which the dynamic regulation would be uncovered. 

PMID- 24739376
TI  - What causes increased expression of VEGF and VEGF-R in a case report? Comment on:
      "New autopsy findings in different brain regions of a preterm neonate with
      kernicterus: neurovascular alterations and up-regulation of efflux transporters".

PMID- 24739377
TI  - Response to the letter to the editor by Mamdouha Ahdab-Barmada and Jon F.
      Watchko.

PMID- 24739378
TI  - Delayed cerebral vasculopathy following cranial radiation therapy for pediatric
      tumors.
AB  - BACKGROUND: Radiation-induced cerebrovascular injury is a well-known phenomenon.
      We analyze reported cases of delayed radiation-induced cerebrovasculopathy that
      present as moyamoya syndrome and/or intracerebral hemorrhage and to statistically
      analyze the relationship between radiation dose and the interval period between
      radiation and the presentation of cerebrovasculopathy. METHODS: Patients ages <21
      years at the time of radiation were included in analysis. A review of previous
      publications yielded 77 cases of delayed radiation-induced cerebrovasculopathy
      consisting of 45 cases of moyamoya syndrome, 30 cases of intracerebral
      hemorrhage, and two cases of both. RESULTS: The median age at radiation was 4.8
      years, with a range of 0.5-20 years. Approximately, 75% of these patients
      received radiation at the age of <9 years. The median interval period for
      moyamoya cases was 3.3 years (range: 0.3-20; P < 0.001), whereas the median
      interval period from radiation to presentation for intracerebral hemorrhage cases
      was 7.5 years (range: 0.8-27). There was significant association between
      radiation dose and interval from radiation to moyamoya syndrome (P < 0.001),
      whereas for patients with intracerebral hemorrhage, the association was
      insignificant (P = 0.31). CONCLUSIONS: Pediatric patients who presented with
      moyamoya generally presented earlier than those who presented with intracerebral
      hemorrhage, suggesting that moyamoya may be a factor that predisposes the patient
      to intracerebral hemorrhage. In patients who presented with moyamoya, there was a
      statistically significant correlation between increasing doses of radiation and
      shorter time from radiation to disease presentation.

PMID- 24739379
TI  - Anti-N-methyl-D-aspartate receptor encephalitis in Taiwan--a comparison between
      children and adults.
AB  - BACKGROUND: Since the discovery of antibodies against the N-methyl-D-aspartate
      receptor in 2007, anti-N-methyl-D-aspartate receptor encephalitis is increasingly
      recognized worldwide. We compare the clinical features of adults and children
      with this disorder in Taiwan. METHODS: Patients admitted to Chang Gung Memorial
      Hospital and Chang Gung Children's Hospital and those who were referred from
      other institutions because of unknown encephalitis from 2009 to 2013 were
      enrolled, and their clinical features were analyzed. Data on cases from a review
      of the literature were also included in the analysis. RESULTS: Twelve patients
      (10 females) aged between 7 years and 28 years with anti-N-methyl-D-aspartate
      receptor encephalitis were identified. Six patients (50%) were <18 years old, one
      of whom was male and three of whom had an underlying tumor. Overall, 91.6% of the
      patients presented with mood, behavioral, or personality changes; 91.6% developed
      seizures; 100% had stereotyped movements; 83.3% had autonomic instability; and
      66.7% had hypoventilation. Responses to immunotherapy were slow and variable.
      Overall, 63.6% of the patients had a substantial recovery after immunotherapy or
      removal of the tumor, and one patient experienced neurological relapses. There
      were no significant differences in clinical manifestations between children and
      adults. CONCLUSIONS: Anti-N-methyl-D-aspartate receptor encephalitis is
      increasingly recognized in Taiwan. It is characterized by its clinical features,
      predominantly affects females with and/or without an ovarian tumor, and it is a
      potentially treatable disorder. It is important for neurologists to be familiar
      with the clinical presentations of the disease in children and young adults.

PMID- 24739380
TI  - Women and academic medicine: a review of the evidence on female representation.

PMID- 24739381
TI  - Resources, indicators, data management, dissemination and use in health
      information systems in sub-Saharan Africa: results of a questionnaire-based
      survey.
AB  - OBJECTIVE: To describe the status of health information systems in 14 sub-Saharan
      African countries of the World Health Organization African Region. DESIGN: A
      questionnaire-based survey. SETTING: Fourteen sub-Saharan African countries of
      the African Region. PARTICIPANTS: Key informants in the ministries of health,
      national statistics offices, health programmes, donors and technical agencies.
      MAIN OUTCOME MEASURES: State of resources, indicators, data sources, data
      management, information products, dissemination and use of health information.
      RESULTS: The highest average score was in the identification and harmonisation of
      indicators (73%), reflecting successful efforts to identify priority indicators
      and reach international consensus on indicators for several diseases. This was
      followed by information products (63%), which indicated the availability of
      accurate and reliable data. The lowest score (41%) was in data management, the
      ability to collect, store, analyse and distribute data, followed by resources -
      policy and planning, human and financial resources, and infrastructure (53%).
      Data sources (e.g. censuses, surveys) were on average inadequate with a score of
      56%. The average score for dissemination and use of health information was 57%,
      which indicated limited or inadequate use of data for advocacy, planning and
      decision-making. CONCLUSIONS: National health information systems are weak in the
      surveyed countries and much more needs to be done to improve the quality and
      relevance of data, and their management, sharing and use for policy-making and
      decision-making.

PMID- 24739382
TI  - The role of mentoring in academic career progression: a cross-sectional survey of
      the Academy of Medical Sciences mentoring scheme.
AB  - : Summary OBJECTIVES: To describe a successful mentoring scheme designed for mid
      career clinician scientists and to examine factors associated with mentee report
      of positive career impact. DESIGN: Mixed methods study including in-depth
      interviews and cross-sectional data collection via an online survey. SETTING:
      Academy of Medical Sciences mentoring scheme set up in 2002 and evaluated in
      2010. PARTICIPANTS: One hundred and forty-seven of 227 mentees took part in the
      study (response rate of 65%). Ten mentees, three mentors and eight
      stakeholders/scheme staff were selected to participate in in-depth interviews.
      MAIN OUTCOME MEASURES: Qualitative data: Interviews were transcribed, and free
      text was analysed to identify themes and subthemes in the narrative. Quantitative
      data: We examined the associations of reported positive career impact of
      mentoring by performing simple and multiple logistic regression analysis.
      RESULTS: Mentoring success was determined by a variety of factors including
      reasons for selection (e.g. presence of a personal recommendation), mentee
      characteristics (e.g. younger age), experience and skills of the mentor (e.g.
      'mentor helped me to find my own solutions') and the quality of the relationship
      (e.g. 'my mentor and I set out clear expectations early on'). CONCLUSIONS: Our
      evaluation demonstrates that both mentor and mentee value mentoring and that
      careful planning of a scheme including preparation, training and ongoing support
      of both mentor and mentee addressing expectations, building rapport and logistics
      are likely to be helpful in ensuring success and benefit from the intervention.

PMID- 24739383
TI  - Medical relevance of UK-funded non-human primate research published from January
      1997 to July 2012.
AB  - In 2012, the Bateson Review of research using non-human primates (NHPs)
      recommended the commissioning of a working group to identify and follow-up the
      results of UK-funded NHP research of potential benefit for human health
      (Recommendation 4), but the Medical Research Council (MRC) has postponed
      implementation of the recommendation. Information on results and potential
      benefits of NHP research therefore remains unavailable. To fill this gap in
      knowledge, this study identified all published NHP research studies funded by the
      MRC, Wellcome Trust and Biotechnology and Biological Sciences Research Council
      (BBSRC) from January 1997 to July 2012 and assessed full texts for medical
      relevance. In total, 284 papers were identified, of which 51 (18%) involved
      invasive NHP research, compared to 176 (61%) which used NHP tissue and cell
      lines, indicating a shift in research emphasis from invasive whole animal to cell
      based research. Of these studies, 98 (35%) were medically relevant, of which 22
      had potential therapeutic or public health applications. The relatively low
      proportion of medical studies together with the small number of applied studies
      raises questions over the level of investment in medical research and the
      effectiveness of knowledge transfer from basic to applied research.
      Implementation of the Bateson Review's Recommendation 4 would address these
      questions.

PMID- 24739384
TI  - Multiple sclerosis autoantigen myelin basic protein escapes control by
      ubiquitination during proteasomal degradation.
AB  - The vast majority of cellular proteins are degraded by the 26S proteasome after
      their ubiquitination. Here, we report that the major component of the myelin
      multilayered membrane sheath, myelin basic protein (MBP), is hydrolyzed by the
      26S proteasome in a ubiquitin-independent manner both in vitro and in mammalian
      cells. As a proteasomal substrate, MBP reveals a distinct and physiologically
      relevant concentration range for ubiquitin-independent proteolysis. Enzymatic
      deimination prevents hydrolysis of MBP by the proteasome, suggesting that an
      abnormally basic charge contributes to its susceptibility toward proteasome
      mediated degradation. To our knowledge, our data reveal the first case of a
      pathophysiologically important autoantigen as a ubiquitin-independent substrate
      of the 26S proteasome. 

PMID- 24739385
TI  - Binding of Streptococcus pneumoniae endopeptidase O (PepO) to complement
      component C1q modulates the complement attack and promotes host cell adherence.
AB  - The Gram-positive species Streptococcus pneumoniae is a human pathogen causing
      severe local and life-threatening invasive diseases associated with high
      mortality rates and death. We demonstrated recently that pneumococcal
      endopeptidase O (PepO) is a ubiquitously expressed, multifunctional plasminogen
      and fibronectin-binding protein facilitating host cell invasion and evasion of
      innate immunity. In this study, we found that PepO interacts directly with the
      complement C1q protein, thereby attenuating the classical complement pathway and
      facilitating pneumococcal complement escape. PepO binds both free C1q and C1
      complex in a dose-dependent manner based on ionic interactions. Our results
      indicate that recombinant PepO specifically inhibits the classical pathway of
      complement activation in both hemolytic and complement deposition assays. This
      inhibition is due to direct interaction of PepO with C1q, leading to a strong
      activation of the classical complement pathway, and results in consumption of
      complement components. In addition, PepO binds the classical complement pathway
      inhibitor C4BP, thereby regulating downstream complement activation. Importantly,
      pneumococcal surface-exposed PepO-C1q interaction mediates bacterial adherence to
      host epithelial cells. Taken together, PepO facilitates C1q-mediated bacterial
      adherence, whereas its localized release consumes complement as a result of its
      activation following binding of C1q, thus representing an additional mechanism of
      human complement escape by this versatile pathogen. 

PMID- 24739386
TI  - Deficiency of nicotinamide mononucleotide adenylyltransferase 3 (nmnat3) causes
      hemolytic anemia by altering the glycolytic flow in mature erythrocytes.
AB  - NAD biosynthesis is of substantial interest because of its important roles in
      regulating various biological processes. Nicotinamide mononucleotide
      adenylyltransferase 3 (Nmnat3) is considered a mitochondria-localized NAD
      synthesis enzyme involved in de novo and salvage pathways. Although the
      biochemical properties of Nmnat3 are well documented, its physiological function
      in vivo remains unclear. In this study, we demonstrated that Nmnat3 was localized
      in the cytoplasm of mature erythrocytes and critically regulated their NAD pool.
      Deficiency of Nmnat3 in mice caused splenomegaly and hemolytic anemia, which was
      associated with the findings that Nmnat3-deficient erythrocytes had markedly
      lower ATP levels and shortened lifespans. However, the NAD level in other tissues
      were not apparently affected by the deficiency of Nmnat3. LC-MS/MS-based
      metabolomics revealed that the glycolysis pathway in Nmnat3-deficient
      erythrocytes was blocked at a glyceraldehyde 3-phosphate dehydrogenase (GAPDH)
      step because of the shortage of the coenzyme NAD. Stable isotope tracer analysis
      further demonstrated that deficiency of Nmnat3 resulted in glycolysis stall and a
      shift to the pentose phosphate pathway. Our findings indicate the critical roles
      of Nmnat3 in maintenance of the NAD pool in mature erythrocytes and the
      physiological impacts at its absence in mice. 

PMID- 24739387
TI  - A novel CD44-binding peptide from the pro-matrix metalloproteinase-9 hemopexin
      domain impairs adhesion and migration of chronic lymphocytic leukemia (CLL)
      cells.
AB  - (pro)MMP-9 binds to CLL cells through the PEX9 domain and contributes to CLL
      progression. To biochemically characterize this interaction and identify
      potential therapeutic targets, we prepared GST-PEX9 forms containing structural
      blades B1B2 or B3B4. We recently described a sequence in blade B4 (P3 sequence)
      that bound alpha4beta1 integrin and partially impaired cell adhesion and
      migration. We have now studied the possible contribution of the B1B2 region to
      cell interaction with PEX9. CLL cells bound to GST-B1B2 and CD44 was the primary
      receptor. GST-B1B2 inhibited CLL cell migration as effectively as GST-B3B4.
      Overlapping synthetic peptides spanning the B1B2 region identified the sequence
      FDAIAEIGNQLYLFKDGKYW, present in B1 and contained in peptide P6, as the most
      effective site. P6 inhibited cell adhesion to PEX9 in a dose-dependent manner and
      with an IC50 value of 90 MUM. P6 also inhibited cell adhesion to hyaluronan but
      had no effect on adhesion to VCAM-1 (alpha4beta1 integrin ligand), confirming its
      specific interaction with CD44. Spatial localization analyses mapped P6 to the
      central cavity of PEX9, in close proximity to the previously identified P3
      sequence. Both P6 and P3 equally impaired cell adhesion to (pro)MMP-9. Moreover,
      P6 synergistically cooperated with P3, resulting in complete inhibition of CLL
      cell binding to PEX9, chemotaxis, and transendothelial migration. Thus, P6 is a
      novel sequence in PEX9 involved in cell-PEX9/(pro)MMP-9 binding by interacting
      with CD44. Targeting both sites, P6 and P3, should efficiently prevent (pro)MMP-9
      binding to CLL cells and its pathological consequences.

PMID- 24739389
TI  - Uracil-DNA glycosylase is involved in DNA demethylation and required for
      embryonic development in the zebrafish embryo.
AB  - Uracil-DNA glycosylase (Ung) is a component of the base excision repair process
      and has the ability to remove uracil from U:G mispairs in DNA. However, its
      implications in development of vertebrate embryos are poorly understood. In this
      study, we found that zebrafish uracil-DNA glycosylase a (Unga) is maternally
      expressed at high levels and accumulated in nuclei during cleavage and
      blastulation periods. Knockdown of unga in zebrafish embryos causes an increase
      of the global DNA methylation level concomitantly with a reduction of overall
      transcriptional activity in the nucleus, ultimately resulting in embryonic
      lethality during segmentation period. Conversely, unga overexpression is
      sufficient to reduce the global DNA methylation level, to increase H3K4me3 and
      H3K27me3 marks, and to activate genome transcription. Furthermore, overexpression
      of unga(D132A) mRNA, encoding a mutant Unga without DNA glycosylase activity,
      does not affect global DNA methylation level, indicating that its involvement in
      DNA demethylation is dependent on its glycosylase activity. These results
      together suggest that Unga is implicated in postfertilization genomic DNA
      demethylation, zygotic gene transcription, and normal embryonic development in
      zebrafish. 

PMID- 24739388
TI  - Rational design of broad spectrum antibacterial activity based on a clinically
      relevant enoyl-acyl carrier protein (ACP) reductase inhibitor.
AB  - Determining the molecular basis for target selectivity is of particular
      importance in drug discovery. The ideal antibiotic should be active against a
      broad spectrum of pathogenic organisms with a minimal effect on human targets.
      CG400549, a Staphylococcus-specific 2-pyridone compound that inhibits the enoyl
      acyl carrier protein reductase (FabI), has recently been shown to possess human
      efficacy for the treatment of methicillin-resistant Staphylococcus aureus
      infections, which constitute a serious threat to human health. In this study, we
      solved the structures of three different FabI homologues in complex with several
      pyridone inhibitors, including CG400549. Based on these structures, we
      rationalize the 65-fold reduced affinity of CG400549 toward Escherichia coli
      versus S. aureus FabI and implement concepts to improve the spectrum of
      antibacterial activity. The identification of different conformational states
      along the reaction coordinate of the enzymatic hydride transfer provides an
      elegant visual depiction of the relationship between catalysis and inhibition,
      which facilitates rational inhibitor design. Ultimately, we developed the novel 4
      pyridone-based FabI inhibitor PT166 that retained favorable pharmacokinetics and
      efficacy in a mouse model of S. aureus infection with extended activity against
      Gram-negative and mycobacterial organisms. 

PMID- 24739390
TI  - The transcription factor GLI1 interacts with SMAD proteins to modulate
      transforming growth factor beta-induced gene expression in a p300/CREB-binding
      protein-associated factor (PCAF)-dependent manner.
AB  - The biological role of the transcription factor GLI1 in the regulation of tumor
      growth is well established; however, the molecular events modulating this
      phenomenon remain elusive. Here, we demonstrate a novel mechanism underlying the
      role of GLI1 as an effector of TGFbeta signaling in the regulation of gene
      expression in cancer cells. TGFbeta stimulates GLI1 activity in cancer cells and
      requires its transcriptional activity to induce BCL2 expression. Analysis of the
      mechanism regulating this interplay identified a new transcriptional complex
      including GLI1 and the TGFbeta-regulated transcription factor, SMAD4. We
      demonstrate that SMAD4 physically interacts with GLI1 for concerted regulation of
      gene expression and cellular survival. Activation of the TGFbeta pathway induces
      GLI1-SMAD4 complex binding to the BCL2 promoter whereas disruption of the complex
      through SMAD4 RNAi depletion impairs GLI1-mediated transcription of BCL2 and
      cellular survival. Further characterization demonstrated that SMAD2 and the
      histone acetyltransferase, PCAF, participate in this regulatory mechanism. Both
      proteins bind to the BCL2 promoter and are required for TGFbeta- and GLI1
      stimulated gene expression. Moreover, SMAD2/4 RNAi experiments showed that these
      factors are required for the recruitment of GLI1 to the BCL2 promoter. Finally,
      we determined whether this novel GLI1 transcriptional pathway could regulate
      other TGFbeta targets. We found that two additional TGFbeta-stimulated genes,
      INTERLEUKIN-7 and CYCLIN D1, are dependent upon the intact GLI1-SMAD-PCAF complex
      for transcriptional activation. Collectively, these results define a novel
      epigenetic mechanism that uses the transcription factor GLI1 and its associated
      complex as a central effector to regulate gene expression in cancer cells. 

PMID- 24739391
TI  - Heat-induced irreversible denaturation of the camelid single domain VHH antibody
      is governed by chemical modifications.
AB  - The variable domain of camelid heavy chain antibody (VHH) is highly heat
      resistant and is therefore ideal for many applications. Although understanding
      the process of heat-induced irreversible denaturation is essential to improve the
      efficacy of VHH, its inactivation mechanism remains unclear. Here, we showed that
      chemical modifications predominantly governed the irreversible denaturation of
      VHH at high temperatures. After heat treatment, the activity of VHH was dependent
      only on the incubation time at 90  degrees C and was insensitive to the number of
      heating (90  degrees C)-cooling (20  degrees C) cycles, indicating a negligible
      role for folding/unfolding intermediates on permanent denaturation. The residual
      activity was independent of concentration; therefore, VHH lost its activity in a
      unimolecular manner, not by aggregation. A VHH mutant lacking Asn, which is
      susceptible to chemical modifications, had significantly higher heat resistance
      than did the wild-type protein, indicating the importance of chemical
      modifications to VHH denaturation. 

PMID- 24739392
TI  - Targeting integrin alpha6 stimulates curative-type bone metastasis lesions in a
      xenograft model.
AB  - Laminin-binding integrin receptors are key mediators of epithelial cell migration
      and tumor metastasis. Recent studies have demonstrated a role for the alpha6
      integrin (ITGA6/CD49f) in maintaining stem cell compartments within normal bone
      marrow and in residency of tumors metastatic to bone. In this study, we tested a
      function-blocking antibody specific for ITGA6, called J8H, to determine if
      preexisting cancer lesions in bone could be slowed and/or animal survival
      improved. Human prostate tumors were established by intracardiac injection into
      male SCID mice and treatment with J8H antibody was initiated after 1 week. Tumor
      progression was monitored by micro-computed tomography (CT) imaging of skeletal
      lesions. Animals that received weekly injections of the anti-ITGA6 antibody
      showed radiographic progression in only 40% of osseous tumors (femur or tibia),
      compared with control animals, where 80% of the lesions (femur or tibia) showed
      progression at 5 weeks. Kaplan-Meier survival analysis demonstrated a significant
      survival advantage for J8H-treated animals. Unexpectedly, CT image analysis
      revealed an increased proportion of bone lesions displaying a sclerotic rim of
      new bone formation, encapsulating the arrested lytic lesions in animals that
      received the anti-ITGA6 antibody treatment. Histopathology of the sclerotic
      lesions demonstrated well-circumscribed tumor within bone, surrounded by
      fibrosis. These data suggest that systemic targeting of the ITGA6-dependent
      function of established tumors in bone may offer a noncytotoxic approach to
      arrest the osteolytic progression of metastatic prostate cancer, thereby
      providing a new therapeutic strategy for advanced disease.

PMID- 24739393
TI  - Evaluation of apoptosis induction by concomitant inhibition of MEK, mTOR, and Bcl
      2 in human acute myelogenous leukemia cells.
AB  - Aberrant activation of multiple signaling pathways is common in acute myelogenous
      leukemia (AML) cells, which can be linked to a poor prognosis for patients with
      this disease. Previous research with mTOR or MEK inhibitors revealed cytostatic,
      rather than cytotoxic, effects in in vitro and in vivo AML models. We evaluated
      the combination effect of the mTOR inhibitor AZD8055 and the MEK inhibitor
      selumetinib on human AML cell lines and primary AML samples. This combination
      demonstrated synergistic proapoptotic effects in AML cells with high basal
      activation of MEK and mTOR. We next incorporated the BH3 mimetic ABT-737 into
      this combination regimen to block Bcl-2, which further enhanced the apoptogenic
      effect of MEK/mTOR inhibition. The combination treatment also had a striking
      proapoptotic effect in CD33(+)/CD34(+) AML progenitor cells from primary AML
      samples with NRAS mutations. Mechanistically, upregulation of the proapoptotic
      protein Bim, accompanied by the downregulation of the antiapoptotic protein Mcl-1
      (mainly via protein degradation), seemed to play critical roles in enhancing the
      combination drug effect. Furthermore, the modulation of survivin, Bax, Puma, and
      X-chromosome-linked inhibitor of apoptosis protein (XIAP) expression suggested a
      role for mitochondria-mediated apoptosis in the cytotoxicity of the drug
      combination. Consequently, the concomitant blockade of prosurvival MEK/mTOR
      signaling and the deactivation of Bcl-2 could provide a mechanism-based
      integrated therapeutic strategy for the eradication of AML cells.

PMID- 24739394
TI  - ABT-737 promotes the dislocation of ER luminal proteins to the cytosol, including
      pseudomonas exotoxin.
AB  - Impaired apoptosis is often a key element in tumor development. Therefore, drugs
      mimicking prosurvival antagonists offer promise as cancer therapeutics. When ABT
      737, a BH3-only mimetic, was added to KB3-1 human cervical adenocarcinoma cells,
      we noted an induction of an endoplasmic reticulum (ER) stress response and the
      dislocation of ER luminal proteins, including chaperones, to the cell cytosol.
      Furthermore, when immunotoxin (antibody-toxin chimeric molecule) and ABT-737
      combinations were added to cells, there was enhanced toxin-mediated inhibition of
      protein synthesis, consistent with enhanced translocation of toxin to the
      cytosol. A similar enhancement was not seen with thapsigargin, suggesting that ER
      stress alone was not responsible for enhanced translocation. Cytosol preparations
      from ABT-737-treated but not from thapsigargin-treated cells revealed the
      presence of greater amounts of processed 37-kDa toxin fragment compared with the
      addition of immunotoxin alone. As early as 4 hours after the addition of ABT-737
      and immunotoxin, there was release of mitochondrial cytochrome c and activation
      of caspase-3/7 indicating that the combination caused apoptotic cell death. These
      results were reflected in decreased cellular ATP levels that were noted with
      combinations of ABT-737 and immunotoxin but not with either agent alone or with
      combinations of thapsigargin and immunotoxin. We conclude that ABT-737 increases
      ER permeability, promoting the dislocation of toxin from the ER to the cytosol
      resulting in early apoptotic cell death. These mechanistic insights suggest why
      this class of BH3-only mimetic synergizes in a particular way with Pseudomonas
      exotoxin-based immunotoxins.

PMID- 24739395
TI  - Health care seeking patterns and out of pocket payments for children under five
      years of age living in Katchi Abadis (slums), in Islamabad, Pakistan.
AB  - BACKGROUND: Since 1990, Pakistan has faced an unprecedented rate of urbanization,
      thereby resulting in the uncontrolled proliferation of slums (Katchi Abadis) in
      all large cities. These areas lack the basic municipal services such as safe
      water supply, sanitation and waste collection. There is limited access to quality
      health care services, both curative and preventive. Therefore, communities living
      in katchi abadis are faced with health seeking challenges and catastrophic
      expenditure to pay for health care services (formal or informal). METHODS: This
      cross-sectional quantitative study was conducted in Islamabad, using a semi
      structured questionnaire with mothers of children 5 years of age. There are 34
      katchi abadis, 11 are recognized by the Capital Development Authority, out of
      which seven were included in the study. The calculated sample size was 207. MAIN
      FINDINGS: Average household income was found to be Pak Rupee 10,000
      (approx.US$100) per month. Diarrhea, fever, common cold and cough were common
      illnesses among under 5 children. Approximately 43% of the mothers were
      illiterate and they preferred consulting a private doctor or a private dispenser
      in the katchi abadi. Mother's level of education was significantly associated
      with the type of health provider consulted. Majority had to spend out of pocket,
      while many either borrowed money from relatives or friends or sold a household
      item. Delay in seeking health care added to the out of pocket expense. The mean
      cost on child's treatment was approximately PkRs400 (approximately US$ 4) for a
      single consultation. CONCLUSION: There are several factors associated with health
      seeking behavior of mothers of children under the age of 5 years, living in the
      katchi abadis of Islamabad. The latter population group is one of the most
      vulnerable given their poor standard of living conditions. A multi-sectoral
      approach is needed to address the provision of basic amenities, the availability
      of safety nets to pay for health care is crucial to avoid catastrophic
      expenditure and the provision of community-based health promotion programs are
      essential to improve health seeking behaviors whilst simultaneously promoting and
      protecting health.

PMID- 24739396
TI  - MaterialVis: material visualization tool using direct volume and surface
      rendering techniques.
AB  - Visualization of the materials is an indispensable part of their structural
      analysis. We developed a visualization tool for amorphous as well as crystalline
      structures, called MaterialVis. Unlike the existing tools, MaterialVis represents
      material structures as a volume and a surface manifold, in addition to plain
      atomic coordinates. Both amorphous and crystalline structures exhibit topological
      features as well as various defects. MaterialVis provides a wide range of
      functionality to visualize such topological structures and crystal defects
      interactively. Direct volume rendering techniques are used to visualize the
      volumetric features of materials, such as crystal defects, which are responsible
      for the distinct fingerprints of a specific sample. In addition, the tool
      provides surface visualization to extract hidden topological features within the
      material. Together with the rich set of parameters and options to control the
      visualization, MaterialVis allows users to visualize various aspects of materials
      very efficiently as generated by modern analytical techniques such as the Atom
      Probe Tomography.

PMID- 24739397
TI  - Easy washing of lysed cell plugs for bacterial typing by pulsed-field gel
      electrophoresis using simple equipment.
AB  - We designed and tested equipment to wash plugs following cell lysis in pulsed
      field gel electrophoresis (PFGE). Our system can wash 30 plugs simultaneously in
      1h using 15L of Tris-EDTA buffer, which makes plug washing for PFGE less labor
      intensive. 

PMID- 24739398
TI  - Risk-proportionate clinical trial monitoring: an example approach from a non
      commercial trials unit.
AB  - BACKGROUND: Some level of monitoring is usually required during a clinical trial
      to protect the rights and safety of trial participants and to safeguard the
      quality and reliability of trial results. Although there is increasing support
      for the use of risk-proportionate approaches to achieve these aims, the variety
      of methods and lack of an empirical evidence base can present challenges for
      clinical trial practitioners. METHODS: This paper describes the monitoring
      methods and procedures that are utilised by a non-commercial clinical trials unit
      which coordinates a range of clinical trials across a variety of clinical areas
      with different associated risks. RESULTS: Monitoring activities and approaches
      should be selected to be proportionate to the risks identified within a trial. A
      risk-proportionate approach to monitoring is described giving details of methods
      that may be considered by clinical trial practitioners during the development of
      a trial monitoring plan. An example risk assessment and corresponding monitoring
      plan for a low risk (type A in the Medicines and Healthcare Products Regulatory
      Agency (MHRA) classification system) pediatric trial is provided for
      illustration. CONCLUSION: We present ideas for developing a monitoring plan for a
      clinical trial of an investigational medicinal product based on our experience.
      Alternative approaches may be relevant or preferable in other settings based on
      inherent risk.

PMID- 24739400
TI  - Diagnosis of natalizumab-associated progressive multifocal leukoencephalopathy
      using MRI.
AB  - PURPOSE OF REVIEW: This review describe the role and advancements of MRI in the
      diagnosis and monitoring of progressive multifocal leukoencephalopathy (PML) in
      multiple sclerosis patients treated with natalizumab. RECENT FINDINGS: MRI is the
      most sensitive paraclinical tool in the detection of PML lesions in natalizumab
      treated multiple sclerosis patients, showing lesions in very early disease stages
      up to months before clinical symptoms occur. The sensitivity of PML lesion
      detection is dependent on the MRI pulse-sequences used. Fluid-attenuated
      inversion recovery shows the highest sensitivity and diffusion-weighted MRI is
      well suited to depict active and acute demyelination in PML lesions. Compared
      with the PML in HIV-infected patients, the MRI appearance of natalizumab
      associated PML is rather heterogeneous and fluctuating, including signs of
      inflammation and showing new imaging patterns such as cortical grey matter
      involvement. The importance of reliable PML detection is particularly obvious in
      patients at an asymptomatic stage. The clinical relevance of natalizumab
      associated PML detected at an asymptomatic stage is best illustrated by the fact
      that such patients have a substantially better outcome compared with symptomatic
      PML patients. SUMMARY: MRI is the most powerful method in the detection of
      natalizumab-associated PML by showing imaging patterns helpful in the
      differentiation between PML and multiple sclerosis lesions. The early -
      preferably asymptomatic - detection of PML is related to a more favorable outcome
      in terms of survival and functional outcome parameters.

PMID- 24739399
TI  - Molecular analysis of common polymorphisms within the human Tyrosinase locus and
      genetic association with pigmentation traits.
AB  - We have compared the melanogenic activities of cultured melanocytes carrying two
      common TYR alleles as homozygous 192S-402R wild-type, heterozygous and homozygous
      variant. This includes assays of TYR protein, DOPAoxidase activity, glycosylation
      and temperature sensitivity of protein and DOPAoxidase levels. Homozygous wild
      type strains on average had higher levels of TYR protein and enzyme activity than
      other genotypes. Homozygous 402Q/Q melanocytes produced significantly less TYR
      protein, displayed altered trafficking and glycosylation, with reduced
      DOPAoxidase. However, near wild-type TYR activity levels could be recovered at
      lower growth temperature. In a sample population from Southeast Queensland, these
      two polymorphisms were present on four TYR haplotypes, designated as WT 192S
      402R, 192Y-402R and 192S-402Q with a double-variant 192Y-402Q of low frequency at
      1.9%. Based on cell culture findings and haplotype associations, we have used an
      additive model to assess the penetrance of the ten possible TYR genotypes derived
      from the combination of these haplotypes.

PMID- 24739402
TI  - The need for a multiple sclerosis registry in the Gulf Region.

PMID- 24739401
TI  - The addition of rituximab to CHOP therapy alters the prognostic significance of
      CD44 expression.
AB  - Expression of CD44 splice isoforms has been previously reported to correlate with
      inferior outcomes in DLBCL patients treated with CHOP therapy. However, it is
      unclear whether this observation remains valid in the R-CHOP era. In this study,
      we correlated CD44H and CD44v6 status with survival outcomes among DLBCL patients
      with an emphasis on the comparison between CHOP- and R-CHOP-treated subgroups.
      Our results suggest that rituximab has significantly decreased the prognostic
      value of CD44H. We also observed that the therapeutic benefit of rituximab is
      largely restricted to CD44H-positive cases in this cohort. 

PMID- 24739403
TI  - Neuroinflammation: Contemporary anti-inflammatory treatment approaches.
AB  - We investigated the idea of possible anti-inflammatory treatment approaches for
      inflammatory disorders in the CNS. The articles used for this review were
      searched through PubMed, PsycINFO, and Google scholar and published between
      January 2000 and July 2013. The CNS has its own type of defensive mechanism. The
      crosstalk between neurons and the immune system take place via small molecules
      called cytokines that are secreted from glial cells. Previous study suggested
      that the imbalance of cytokines facilitates the development of CNS disorders. For
      instance, the interleukin-6 level is raised in the astrocyte cell during
      depressive episodes, while axons are damaged by the activated lymphocytes and
      microglia in multiple sclerosis. Several studies demonstrated that cytokines and
      inflammatory compounds are closely linked to neuropsychiatric and
      neurodegenerative disorders. Here, we have accumulated and summarized evidence
      from those papers that support the anti-inflammatory treatment options for
      inflammatory CNS disorders. 

PMID- 24739404
TI  - Pediatric brainstem tumors. Classifications, investigations, and growth patterns.
AB  - Brainstem gliomas occur in 10-20% of brain tumors in pediatrics. Over the past 3
      decades, the treatment of brainstem gliomas has significantly progressed as a
      result of the gradual advancements in microsurgical techniques, sophisticated
      imaging technology and, most importantly, the availability of MRI. In this
      article, we review the current literature on brainstem gliomas and cover
      diagnosis, imaging, classification, and management. Surgical approaches and
      intraoperative modalities to tackle operable cases of brainstem gliomas will be
      discussed in a follow up article. 

PMID- 24739405
TI  - Effects of dehydroepiandrosterone in amphetamine-induced schizophrenia models in
      mice.
AB  - OBJECTIVE: To examine the effects of dehydroepiandrosterone (DHEA) on animal
      models of schizophrenia. METHODS: Seventy Swiss albino female mice (25-35 g) were
      divided into 4 groups: amphetamine-free (control), amphetamine, 50, and 100 mg/kg
      DHEA. The DHEA was administered intraperitoneally (ip) for 5 days. Amphetamine (3
      mg/kg ip) induced hyper locomotion, apomorphine (1.5 mg/kg subcutaneously [sc])
      induced climbing, and haloperidol (1.5 mg/kg sc) induced catalepsy tests were
      used as animal models of schizophrenia. The study was conducted at the Animal
      Experiment Laboratories, Department of Pharmacology, Medical School, Eskisehir
      Osmangazi University, Eskisehir, Turkey between March and May 2012. Statistical
      analysis was carried out using Kruskal-Wallis test for hyper locomotion, and one
      way ANOVA for climbing and catalepsy tests. RESULTS: In the amphetamine-induced
      locomotion test, there were significant increases in all movements compared with
      the amphetamine-free group. Both DHEA 50 mg/kg (p<0.05), and 100 mg/kg (p<0.01)
      significantly decreased all movements compared with the amphetamine-induced
      locomotion group. There was a significant difference between groups in the
      haloperidol-induced catalepsy test (p<0.05). There was no significant difference
      between groups in terms of total climbing time in the apomorphine-induced
      climbing test (p>0.05). CONCLUSION: We observed that DHEA reduced locomotor
      activity and increased catalepsy at both doses, while it had no effect on
      climbing behavior. We suggest that DHEA displays typical neuroleptic-like
      effects, and may be used in the treatment of schizophrenia.

PMID- 24739406
TI  - Beneficial effects of edaravone on the expression of serum matrix
      metalloproteinase-9 after cerebral hemorrhage.
AB  - OBJECTIVE: To explore the effects of edaravone on the expression of matrix
      metalloproteinase-9 (MMP-9) posterior to cerebral hemorrhage, and to analyze the
      relationship between this expression and neurological deficit. METHODS: A total
      of 160 basal ganglia hemorrhage patients enrolled in Dongfeng Hospital, Hubei
      University of Medicine, Shiyan, China between April 2009 and July 2011 were
      included and divided into a treatment group and a control group (n=80). All
      patients were treated with minimally invasive hematoma evacuation, and the
      treatment group was administered with edaravone simultaneously. Serum MMP-9
      levels were measured by double-antibody sandwich enzyme-linked immunosorbent
      assay. The National Institutes of Health Stroke Scale (NIHSS) and Glasgow Coma
      Scale scores of the 2 groups were determined before and after treatment. RESULTS:
      The overall effective rates of the treatment (86.3%) and control (75.0%) groups
      differed significantly (p<0.05). The serum MMP-9 levels of the 2 groups that were
      similar (p>0.05) before treatment significantly decreased (p<0.05) after
      treatment, and those of the 2 groups also differed significantly (p<0.05). The
      NIHSS scores of the 2 groups that were similar (p>0.05) before treatment also
      significantly decreased (p<0.05) after treatment, and those of the 2 groups
      differed significantly (p<0.05). Pearson's correlation analysis revealed that the
      level of serum MMP-9 was significantly correlated with the NIHSS score before
      treatment (R=0.491). CONCLUSION: Combined minimally invasive hematoma evacuation
      and edaravone effectively treated cerebral hemorrhage by directly lowering the
      level of serum MMP-9.

PMID- 24739407
TI  - Venous thrombosis of the brain. Retrospective review of 110 patients in Kuwait.
AB  - OBJECTIVE: To highlight the importance of neurological presentation and
      complications in the early diagnosis and management of cerebral venous thrombosis
      (CVT). METHODS: We performed a retrospective case analysis of 110 patients with
      CVT treated at the Neurology Center, Ibn Sina Hospital, in Kuwait from January
      2000 to September 2013. The records of patients with CVT were retrieved and
      entered in a data sheet. The different neurological presenting signs and symptoms
      were analyzed based on their frequency, pathogenesis, and treatment. RESULTS: One
      hundred and ten (110) patients were included in this study, with a male to female
      ratio of 1:1.7. Neurological signs and symptoms were headache (82%), seizures
      (42%), and focal neurological deficits (33%). Papilledema with raised
      intracranial pressure was recorded in 35 patients (32%). Venous and hemorrhagic
      venous infarctions were recorded in 27 patients, and multiple intracerebral or
      subarachnoid hemorrhages in 7 patients. The venous sinuses involved were the
      superior sagittal sinus in 54.5%, and transverse sigmoid sinuses in 52%.
      CONCLUSION: Headache, seizures, and focal neurological deficits were the most
      common neurological presentation. Anticoagulants (systemic heparin) were used as
      first-line therapy, including patients with intracerebral hemorrhage. The use of
      steroids and osmotic diuretics as anti-edema measures were recorded in 25% of
      cases. Treating raised ICP by repeated lumbar puncture and CSF drain could
      prevent visual failure.

PMID- 24739408
TI  - The impact of pneumonia on hospital stay among patients hospitalized for acute
      stroke.
AB  - OBJECTIVE: To determine the impact of pneumonia on length of hospital stay in
      cases of acute stroke. METHODS: This was a retrospective cross-sectional study on
      368 stroke patients admitted with a diagnosis of stroke at the Avicenna Hospital,
      Qazvin, Iran between January 2010 and March 2011. By reviewing the hospital
      patient records, the demographic characteristics, stroke characteristics, and
      complications of stroke in these patients were determined during their hospital
      stay. In surviving patients, the impact of each variable on length of hospital
      stay was calculated by logistic regression analysis and the Log-Rank test.
      RESULTS: Patients with pneumonia during the post stroke period had an increased
      length of hospital stay (11.5+/-6.4 days), compared with other patients (7.2+/
      4.1 days), (p=0.0005). Multiple logistic regression analysis showed a significant
      association between length of hospital stay and urinary tract infection
      (p=0.001), steroid consumption (p=0.028), index of stroke severity (p=0.039),
      pneumonia (p=0.042), and swallowing disorder (p=0.048). CONCLUSION: Considering
      the impact of pneumonia on the length of hospital stay and its consequences,
      prophylactic activities, rapid diagnosis, and treatment of pneumonia may improve
      outcome and reduce costs in stroke patients.

PMID- 24739409
TI  - Public awareness and attitudes toward epilepsy in Saudi Arabia is improving.
AB  - OBJECTIVE: To examine public awareness and attitudes toward epilepsy in Riyadh,
      the capital city of Saudi Arabia. METHODS: A focused 10-item questionnaire was
      designed to survey public awareness and attitudes toward epilepsy. Personal
      interviews were conducted randomly by one author in preselected public places in
      Riyadh, Saudi Arabia during March and April 2011. RESULTS: Seven hundred and
      forty-nine interviews were completed during the study period. Most participants
      (77.4%) had prior knowledge of epilepsy, and 52% believed that epilepsy is an
      organic disease. This correlated with their educational level, as those with
      higher levels of education were more likely to link epilepsy to organic causes
      (p=0.008). However, 15% also linked epilepsy to evil spirit possession, and up to
      37% preferred spiritual rituals and religious healing to medical treatments.
      Although most respondents (61%) would accept an epileptic patient in a regular
      job, 71% (particularly males) reported reservations in marrying someone with
      epilepsy (p=0.001). CONCLUSION: The awareness and attitudes of the Saudi public
      toward epilepsy are showing some improvement. However, it is still thought to be
      linked to evil spirit possession by some, and spiritual rituals and religious
      healing are commonly believed to be effective treatments. Targeted areas for
      focused education were identified.

PMID- 24739410
TI  - Cerebral sinus venous thrombosis in a child with nephrotic syndrome.
AB  - Cerebral venous thrombosis (CVT) as a complication in children with nephrotic
      syndrome is rarely reported. Although clinical characteristics are increasingly
      recognized, therapeutic management and clinical outcomes are not well documented.
      This case report presents a 10-year-old female who presented with dehydration
      associated with headache and decreased level of consciousness, which required
      intubation. Brain imaging revealed CVT. Thrombolytic therapy was started, and she
      showed a good clinical, as well as radiological recovery. The literature was
      reviewed to highlight the benefit of such therapy in cases with life threatening
      complications. 

PMID- 24739411
TI  - Unusual heat stroke caused by herbal therapy with traditional Chinese medicine.
AB  - Traditional Chinese medicine (TCM) comprises a range of traditional medical
      practices that originate in China, including herbal medicine as a major therapy.
      Through its 4 natures; namely, cold, hot, warm, and cool, herbal medicine may
      regulate sympathetic nerves and basal metabolic rate and affect the CNS and the
      endocrine system. Heat stroke is a severely life-threatening heat-related illness
      that is most commonly seen during summer heat waves and high environmental
      temperatures. The intake of medications or toxins is considered one of the risk
      factors leading to heat stroke, as they may affect body thermoregulation. We
      report a case of heat stroke that was associated with herbal therapy with TCM.
      This case highlights the importance of paying more attention to unidentified folk
      prescriptions in the use of TCM. 

PMID- 24739412
TI  - Central nervous system involvement in primary Sjogren's syndrome manifesting as
      multiple sclerosis.
AB  - Central nervous system symptoms in patients with primary Sjogren's syndrome are
      rare. They can present as extraglandular manifestations and require a
      differential diagnosis from multiple sclerosis. Due to a variety of
      presentations, Sjogren's syndrome with neurologic involvement may be difficult to
      diagnose. Here, we report a case of a 75-year-old woman who was first diagnosed
      with multiple sclerosis in 2010, but who was subsequently diagnosed with primary
      Sjogren's syndrome 2 years later after showing signs of atypical neurologic
      manifestations. Therefore, primary Sjogren's syndrome should be suspected in
      patients who present with atypical clinical and radiologic neurologic
      manifestations. 

PMID- 24739413
TI  - A broken catheter in the epidural space.
AB  - The Arrow FlexTip epidural catheter has reinforced coiled stainless steel wire,
      which facilitates its insertion and is less likely to puncture the blood vessels.
      However, as compared with non-reinforced, reinforced epidural catheters are more
      vulnerable to break. We report a case from Saudi Arabia on a retained fragment of
      a broken epidural catheter. Measures to prevent this mishap and its management
      are discussed. 

PMID- 24739414
TI  - Lipofibromatous hamartoma in the ulnar nerve of the forearm.

PMID- 24739415
TI  - A child with leukemia and behavioral changes.
AB  - A 12-year-old Saudi girl, known case of T-cell leukemia with CNS relapse. She was
      diagnosed 2 years ago. Multiple cycles of chemotherapy had been used
      (Fludarabine, Cytarabine, Methotrexate, Cyclosporine, and Mercaptopurine). She
      was admitted electively for cord blood transplantation. Afterward, she developed
      visual, and behavioral change followed by seizure. 

PMID- 24739416
TI  - The TRAF3 adaptor protein drives proliferation of anaplastic large cell lymphoma
      cells by regulating multiple signaling pathways.
AB  - T cells devoid of tumor necrosis factor receptor associated factor-3 (Traf3)
      exhibit decreased proliferation, sensitivity to apoptosis, and an improper
      response to antigen challenge. We therefore hypothesized that TRAF3 is critical
      to the growth of malignant T cells. By suppressing TRAF3 protein in different
      cancerous T cells, we found that anaplastic large cell lymphoma (ALCL) cells
      require TRAF3 for proliferation. Since reducing TRAF3 results in aberrant
      activation of the noncanonical nuclear factor-kappaB (NF-kappaB) pathway, we
      prevented noncanonical NF-kappaB signaling by suppressing RelB together with
      TRAF3. This revealed that TRAF3 regulates proliferation independent of the
      noncanonical NF-kappaB pathway. However, suppression of NF-kappaB-inducing kinase
      (NIK) along with TRAF3 showed that high levels of NIK have a partial role in
      blocking cell cycle progression. Further investigation into the mechanism by
      which TRAF3 regulates cell division demonstrated that TRAF3 is essential for
      continued PI3K/AKT and JAK/STAT signaling. In addition, we found that while NIK
      is dispensable for controlling JAK/STAT activity, NIK is critical to regulating
      the PI3K/AKT pathway. Analysis of the phosphatase and tensin homolog (PTEN)
      showed that NIK modulates PI3K/AKT signaling by altering the localization of
      PTEN. Together our findings implicate TRAF3 as a positive regulator of the
      PI3K/AKT and JAK/STAT pathways and reveal a novel function for NIK in controlling
      PI3K/AKT activity. These results provide further insight into the role of TRAF3
      and NIK in T cell malignancies and indicate that TRAF3 differentially governs the
      growth of B and T cell cancers. 

PMID- 24739418
TI  - Carrier multiplication in graphene under Landau quantization.
AB  - Carrier multiplication is a many-particle process giving rise to the generation
      of multiple electron-hole pairs. This process holds the potential to increase the
      power conversion efficiency of photovoltaic devices. In graphene, carrier
      multiplication has been theoretically predicted and recently experimentally
      observed. However, due to the absence of a bandgap and competing phonon-induced
      electron-hole recombination, the extraction of charge carriers remains a
      substantial challenge. Here we present a new strategy to benefit from the gained
      charge carriers by introducing a Landau quantization that offers a tunable
      bandgap. Based on microscopic calculations within the framework of the density
      matrix formalism, we report a significant carrier multiplication in graphene
      under Landau quantization. Our calculations reveal a high tunability of the
      effect via externally accessible pump fluence, temperature and the strength of
      the magnetic field. 

PMID- 24739417
TI  - A nuclear-encoded chloroplast protein harboring a single CRM domain plays an
      important role in the Arabidopsis growth and stress response.
AB  - BACKGROUND: Although several chloroplast RNA splicing and ribosome maturation
      (CRM) domain-containing proteins have been characterized for intron splicing and
      rRNA processing during chloroplast gene expression, the functional role of a
      majority of CRM domain proteins in plant growth and development as well as
      chloroplast RNA metabolism remains largely unknown. Here, we characterized the
      developmental and stress response roles of a nuclear-encoded chloroplast protein
      harboring a single CRM domain (At4g39040), designated CFM4, in Arabidopsis
      thaliana. RESULTS: Analysis of CFM4-GFP fusion proteins revealed that CFM4 is
      localized to chloroplasts. The loss-of-function T-DNA insertion mutants for CFM4
      (cfm4) displayed retarded growth and delayed senescence, suggesting that CFM4
      plays a role in growth and development of plants under normal growth conditions.
      In addition, cfm4 mutants showed retarded seed germination and seedling growth
      under stress conditions. No alteration in the splicing patterns of intron
      containing chloroplast genes was observed in the mutant plants, but the
      processing of 16S and 4.5S rRNAs was abnormal in the mutant plants. Importantly,
      CFM4 was determined to possess RNA chaperone activity. CONCLUSIONS: These results
      suggest that the chloroplast-targeted CFM4, one of two Arabidopsis genes encoding
      a single CRM domain-containing protein, harbors RNA chaperone activity and plays
      a role in the Arabidopsis growth and stress response by affecting rRNA processing
      in chloroplasts.

PMID- 24739419
TI  - Protective factors against suicide among young-old Chinese outpatients.
AB  - BACKGROUND: Suicide is common among the elderly worldwide. However, no literature
      could be found on the beliefs/expectations that protect young-old people from
      attempting suicide. The purpose of this study was to explore young-old
      outpatients' reasons for not killing themselves in Taiwan. METHOD: Data for this
      qualitative descriptive study were extracted from a large research series. From
      the 83 elderly outpatients in the original sample, 31 were chosen for this study
      because they were young-old (65-74 years old) and from two randomly selected
      medical centers in northern Taiwan. Data on participants' reasons for not killing
      themselves in unhappy situations were collected in individual interviews using a
      semi-structured guide and analyzed by content analysis. RESULTS: Analysis of
      interview data identified six major themes: satisfied with one's life, suicide
      cannot resolve problems, fear of humiliating one's children, religious beliefs,
      never thought about suicide, and living in harmony with nature. CONCLUSION: These
      identified protective factors (reasons for living) could be added to suicide
      prevention programs for the elderly. Our findings may also serve as a reference
      for geriatric researchers in western countries with increasing numbers of elderly
      ethnic minority immigrants.

PMID- 24739420
TI  - On-treatment low serum HBV RNA level predicts initial virological response in
      chronic hepatitis B patients receiving nucleoside analogue therapy.
AB  - BACKGROUND: Serum HBV RNA is detectable during nucleoside/nucleotide analogue
      therapy as a result of unaffected RNA replicative intermediates or interrupted
      reverse transcription. We studied the predictive value of serum HBV RNA for
      initial virological response during nucleoside analogue therapy. METHODS: Serum
      HBV RNA was quantified before and at 12 and 24 weeks of lamivudine or entecavir
      therapy. Serum HBV DNA was measured every 4-12 weeks during treatment to define
      initial virological response. RESULTS: Serum HBV RNA was detectable in 21 of 52
      (40%) consecutive patients with a mean of 5.2 log copies/ml (male/female 35/17,
      mean age of 60 years with a range of 31-82, 44% HBeAg-positive, and 26 with
      lamivudine and 26 with entecavir) before treatment. Serum HBV RNA level at week
      12 in patients with an interval from detectable to undetectable serum HBV DNA
      level <16 weeks was significantly lower than those with an interval >=16 weeks
      (3.8 +/-3.8 versus 6.6 +/-3.5 log copies/ml, P=0.013). After adjustment for serum
      HBV DNA level at week 12, serum quantatitive HBsAg level at week 12 and
      pretreatment ALT level, low serum HBV RNA level at week 12 predicted a shorter
      interval to undetectable serum HBV DNA level (adjusted hazard ratio =0.908, 95%
      CI 0.829, 0.993, P=0.035). CONCLUSIONS: Low serum HBV RNA level at week 12 of
      nucleoside analogue therapy independently predicts initial virological response
      in treated chronic hepatitis B patients. Serum HBV RNA levels may thus be useful
      for optimizing treatment of chronic hepatitis B.

PMID- 24739421
TI  - Advanced practice nursing in child maltreatment: practice characteristics.
AB  - INTRODUCTION: Child maltreatment is a problem of epidemic proportions in the
      United States. Pediatric nurse practitioners and other advanced practice nurses
      (APNs) have been caring for maltreated children for decades, yet to date no
      comprehensive assessment of their practice characteristics or their clinical and
      academic contributions to the field has been performed. The purpose of this study
      is to describe the practice characteristics of APNs who care for maltreated
      children. METHOD: A descriptive design was used for this study. Child advocacy
      centers and children's hospitals were contacted to inquire about employment of
      child maltreatment APNs in their institution, and contact information for the
      lead APN was obtained. The Nurse Practitioner Survey was then sent to lead APNs
      by e-mail. RESULTS: The majority of APNs who work primarily in child maltreatment
      are pediatric nurse practitioners who work in child advocacy centers. They are
      providing care to children with physical and/or sexual abuse concerns; however,
      APNs provide care for children with all types of child maltreatment concerns.
      DISCUSSION: APNs play a vital role in the care of abused/neglected children.
      Their important contributions include not only clinical care but also the
      provision of clinical and didactic education to other professionals, parents, and
      the public. Research and publication are also essential to their role.

PMID- 24739424
TI  - Osteoarthritis: A review.
AB  - Disabling for nearly 27 million people, osteoarthritis is expected to double by
      the year 2030. Although age is a strong predictor of osteoarthritis, it is not an
      inevitable consequence of aging. Nurse practitioners, frequently the first
      healthcare providers to see patients with osteoarthritis, must be up-to-date on
      current treatment recommendations.

PMID- 24739422
TI  - A multicenter phase I/II study of the BCNU implant (Gliadel((r)) Wafer) for
      Japanese patients with malignant gliomas.
AB  - Carmustine (BCNU) implants (Gliadel((r)) Wafer, Eisai Inc., New Jersey, USA) for
      the treatment of malignant gliomas (MGs) were shown to enhance overall survival
      in comparison to placebo in controlled clinical trials in the United States and
      Europe. A prospective, multicenter phase I/II study involving Japanese patients
      with MGs was performed to evaluate the efficacy, safety, and pharmacokinetics of
      BCNU implants. The study enrolled 16 patients with newly diagnosed MGs and 8
      patients with recurrent MGs. After the insertion of BCNU implants (8 sheets
      maximum, 61.6 mg BCNU) into the removal cavity, various chemotherapies (including
      temozolomide) and radiotherapies were applied. After placement, overall and
      progression-free survival rates and whole blood BCNU levels were evaluated. In
      patients with newly diagnosed MGs, the overall survival rates at 12 months and 24
      months were 100.0% and 68.8%, and the progression-free survival rate at 12 months
      was 62.5%. In patients with recurrent MGs, the progression-free survival rate at
      6 months was 37.5%. There were no grade 4 or higher adverse events noted due to
      BCNU implants, and grade 3 events were observed in 5 of 24 patients (20.8%).
      Whole blood BCNU levels reached a peak of 19.4 ng/mL approximately 3 hours after
      insertion, which was lower than 1/600 of the peak BCNU level recorded after
      intravenous injections. These levels decreased to less than the detection limit
      (2.00 ng/mL) after 24 hours. The results of this study involving Japanese
      patients are comparable to those of previous studies in the United States and
      Europe. 

PMID- 24739425
TI  - Putting onychomycosis under the microscope.

PMID- 24739426
TI  - Evaluation of a scrotal mass.

PMID- 24739427
TI  - Herpes zoster (shingles).

PMID- 24739428
TI  - No high-tech solutions necessary.

PMID- 24739431
TI  - Positive and negative skeletal adaptation in young gymnasts.
AB  - This article discusses how participation in recreational gymnastics can improve
      the skeletal health of young girls in terms of gaining bone mass, strength, and
      density. Additionally, the article investigates negative skeletal adaptations,
      such as overuse injuries and the effects of rigorous training on growth and
      maturity.

PMID- 24739432
TI  - Skin cancer: increasing awareness and screening in primary care.
AB  - Skin cancer screening (SCS) promotes early detection and improves treatment.
      Primary care providers are strategically positioned to provide screenings, yet
      the frequency is low. Strategies to improve SCS include increasing skin cancer
      awareness, targeting high-risk patient populations, and advocating for primary
      care providers to conduct screenings.

PMID- 24739434
TI  - The plasticity of priming phenomenon activates not only common metabolomic
      fingerprint but also specific responses against P. cucumerina.
AB  - Previously we described that different priming stimuli trigger common metabolomic
      responses against P. cucumerina. Furthermore we showed that several primed
      metabolites were present following independent priming inducers such as natural
      constitutive priming promoted by gene mutations and chemical priming induced by
      the beta-aminobutyric acid (BABA). Despite we found a common metabolomic
      fingerprint, in the present research we focus our attention in specific
      metabolites that are primed differentially by a mutation in the NRT2.1 gene (lin1
      mutant) and BABA treatments against P. cucumerina. Around eight hundred compounds
      were overaccumulated in the resistant mutant lin1 and in BABA treated plants upon
      infection. Among them 404 and 412 were specific of each priming condition while
      103 compounds were shared by both. Flavonoids and lignans were specifically
      accumulated in lin1 in response to the fungal attack, while tyrosine, purine
      metabolism, and aromatic carbon degradation compounds were only accumulated in
      BABA primed plants upon infection. However, most metabolites differentially
      accumulated by the two priming conditions belonged to the same metabolic
      pathways, suggesting that different priming stimuli, upon a given biotic stress,
      may stimulate similar pathways but activate specific differences depending on the
      priming stimulus. 

PMID- 24739436
TI  - When is sampling complete? The effects of geographical range and marker choice on
      perceived diversity in Nitzschia palea (Bacillariophyta).
AB  - DNA barcoding, being developed for biomonitoring, requires a database of
      reference sequences and knowledge of how much sequences can deviate before they
      are assigned to separate species. The molecular hunt for hidden species also
      raises the question of species definitions. We examined whether there are
      objective criteria for sequence-based species delimitation in diatoms, using
      Nitzschia palea, an important monophyletic indicator species already known to
      contain cryptic diversity. Strains from a wide geographical range were sequenced
      for 28S rRNA, COI and rbcL. Homogeneity indices and the Chao index failed to
      objectively select a precise number of species existing in N. palea as well as an
      evolutionary method based on coalescence theory. COI always gave higher diversity
      estimations than 28S rRNA or rbcL. Mating data did not provide a precise
      calibration of molecular species thresholds. Rarefaction curves indicated that
      further MOTUs would be detected with more isolates than we sampled (81 clones, 42
      localities). Although some genotypes had intercontinental distributions, there
      was a positive relationship between genetic and geographical distance, suggesting
      even higher richness than we assessed, given that many regions were not sampled.
      Overall, no objective criteria were found for species separation; instead
      barcoding will need a consensual approach to molecular species limits.

PMID- 24739437
TI  - Characterization of PPMUCL1/2/3, three members of a new oomycete-specific mucin
      like protein family residing in Phytophthora parasitica biofilm.
AB  - The plant pathogen Phytophthora parasitica forms a biofilm on the host surface.
      The biofilm transcriptome is characterized by the expression of PPMUCL1/2/3
      (PHYTOPHTHORA PARASITICA MUCIN-LIKE) genes, which we report here to be members of
      a new, large mucin-like gene family restricted to the oomycete lineage. These
      genes encode secreted proteins organized into two domains. The NH2-terminal
      domain is highly conserved, but of unknown function. The second domain is a mucin
      like domain enriched in threonine and serine residues, with a large number of
      putative O-glycosylation sites and a repeated motif defining 15 subgroups among
      the 315 members of the family. The second domain was found to be glycosylated in
      the recombinant rPPMUCL1 and rPPMUCL2 proteins. An analysis of PPMUCL1/2/3 gene
      expression indicated that these genes were expressed in a specific and
      coordinated manner in the biofilm. A novel cis-motif (R) bound to nuclear
      proteins, suggesting a possible role in PPMUCL1/2/3 gene regulation.
      Immunohistochemical staining revealed that the PPMUCL1/2 proteins were secreted
      and accumulated on the surface of the biofilm. Our data demonstrate that
      PPMUCL1/2/3 belong to a new oomycete-specific family of mucin-like proteins
      playing a structural role in the biofilm extracellular matrix.

PMID- 24739438
TI  - Hypoxic conditions stimulate the release of B-type natriuretic peptide from human
      retinal pigment epithelium cell culture.
AB  - PURPOSE: A-type peptide, a natriuretic peptide belonging to the natriuretic
      peptide family, has been shown to be increased in the vitreous of patients
      suffering from diabetic retinopathy and that human retina has a well-developed
      natriuretic peptide system. The stimulus to which the synthesis of natriuretic
      peptides responded in these patients has, however, remained unknown. As the
      natriuretic peptides have recently been shown to respond to hypoxic conditions,
      the genes of both A-type and B-type have a hypoxia-response element (HRE) in
      their promoter sequence, we therefore hypothesized that hypoxia in the human
      retinal pigment epithelium will increase the secretion of NT-proBNP, the most
      common natriuretic peptide monitored in clinical medicine. METHODS: We used
      cultured human retinal pigment epithelium cell line (ARPE-19) which was exposed
      either to normoxia or to hypoxia for 2 hr, 4 hr, 6 hr and 24 hr. NT-proBNP was
      measured with enzyme immunoassay, VEGF with ELISA and HIF-1alpha with Western
      blotting. RESULTS: Hypoxia induced VEGF 165 release in culture medium and HIF
      1alpha expression in cultured ARPE-19 cells. Time-dependent NT-proBNP release was
      detected when the ARPE-19 cells were cultured under normoxia. When hypoxia was
      induced, a statistically significant increase in NT-proBNP release was
      demonstrated in the culture medium. CONCLUSIONS: Hypoxic conditions increase the
      release of a natriuretic peptide from retinal pigment epithelium (RPE) cells. The
      secretion of VEGF was also enhanced. The responses were associated with the up
      regulation of the HIF-1alpha transcription factor. These results explain the
      previous findings from patients with diabetes, which also suggest that hypoxia is
      a ubiquitous stimulus for the secretion of natriuretic peptides in human body.

PMID- 24739435
TI  - Genetic psychophysiology: advances, problems, and future directions.
AB  - This paper presents an overview of historical advances and the current state of
      genetic psychophysiology, a rapidly developing interdisciplinary research linking
      genetics, brain, and human behavior, discusses methodological problems, and
      outlines future directions of research. The main goals of genetic
      psychophysiology are to elucidate the neural pathways and mechanisms mediating
      genetic influences on cognition and emotion, identify intermediate brain-based
      phenotypes for psychopathology, and provide a functional characterization of
      genes being discovered by large association studies of behavioral phenotypes.
      Since the initiation of this neurogenetic approach to human individual
      differences in the 1970s, numerous twin and family studies have provided strong
      evidence for heritability of diverse aspects of brain function including resting
      state brain oscillations, functional connectivity, and event-related neural
      activity in a variety of cognitive and emotion processing tasks, as well as
      peripheral psychophysiological responses. These data indicate large differences
      in the presence and strength of genetic influences across measures and domains,
      permitting the selection of heritable characteristics for gene finding studies.
      More recently, candidate gene association studies began to implicate specific
      genetic variants in different aspects of neurocognition. However, great caution
      is needed in pursuing this line of research due to its demonstrated proneness to
      generate false-positive findings. Recent developments in methods for
      physiological signal analysis, hemodynamic imaging, and genomic technologies
      offer new exciting opportunities for the investigation of the interplay between
      genetic and environmental factors in the development of individual differences in
      behavior, both normal and abnormal. 

PMID- 24739439
TI  - Polymeric molecular sieve membranes via in situ cross-linking of non-porous
      polymer membrane templates.
AB  - High-performance polymeric membranes for gas separation are attractive for
      molecular-level separations in industrial-scale chemical, energy and
      environmental processes. Molecular sieving materials are widely regarded as the
      next-generation membranes to simultaneously achieve high permeability and
      selectivity. However, most polymeric molecular sieve membranes are based on a few
      solution-processable polymers such as polymers of intrinsic microporosity. Here
      we report an in situ cross-linking strategy for the preparation of polymeric
      molecular sieve membranes with hierarchical and tailorable porosity. These
      membranes demonstrate exceptional performance as molecular sieves with high gas
      permeabilities and selectivities for smaller gas molecules, such as carbon
      dioxide and oxygen, over larger molecules such as nitrogen. Hence, these
      membranes have potential for large-scale gas separations of commercial and
      environmental relevance. Moreover, this strategy could provide a possible
      alternative to 'classical' methods for the preparation of porous membranes and,
      in some cases, the only viable synthetic route towards certain membranes.

PMID- 24739440
TI  - Evaluation of the effects of hyaluronic acid-carboxymethyl cellulose barrier on
      ovarian tumor progression.
AB  - BACKGROUND: Hyaluronic acid is a prognostic factor in ovarian cancers. It is also
      a component of Hyaluronic Acid-Carboxymethyl Cellulose (HA-CMC) barrier, an anti
      adhesion membrane widely used during abdominal surgeries in particular for
      ovarian carcinosis. 70% of patients who undergo ovarian surgery will relapse due
      to the persistence of cancer cells. This study's objective was to determine the
      oncological risk from use of this material, in the presence of residual disease,
      despite the benefit gained by it decreasing post-surgical adhesions in order to
      provide an unambiguous assessment of its appropriateness for use in ovarian
      surgical management. METHODS: We assessed the effects of HA-CMC barrier on the in
      vitro proliferation of human ovarian tumor cell lines (OVCAR-3, IGROV-1 and SKOV
      3). We next evaluated, in vivo in nude mice, the capacity of this biomaterial to
      regulate the tumor progression of subcutaneous and intraperitoneal models of
      ovarian tumor xenografts. RESULTS: We showed that HA-CMC barrier does not
      increase in vitro proliferation of ovarian cancer cell lines compared to control.
      In vivo, HA-CMC barrier presence with subcutaneous xenografts induced neither an
      increase in tumor volume nor cell proliferation (Ki67 and mitotic index). With
      the exception of an increased murine carcinosis score in peritoneum, the presence
      of HA-CMC barrier with intraperitoneal xenografts modified neither macro nor
      microscopic tumor growth. Finally, protein analysis of survival (Akt),
      proliferation (ERK) and adhesion (FAK) pathways highlighted no activation on the
      xenografts imputable to HA-CMC barrier. CONCLUSIONS: For the most part, our
      results support the lack of tumor progression activation due to HA-CMC barrier.
      We conclude that the benefits gained from using HA-CMC barrier membrane during
      ovarian cancer surgeries seem to outweigh the potential oncological risks.

PMID- 24739441
TI  - A community-based approach to indigent selection is difficult to organize in a
      formal neighbourhood in Ouagadougou, Burkina Faso: a mixed methods exploratory
      study.
AB  - BACKGROUND: In most African countries, indigents treated at public health centres
      are supposed to be exempted from user fees. In Africa, most of the available
      knowledge has to do with targeting processes in rural areas, and little is known
      about how to select the worst-off in an urban area. In rural communities of
      Burkina Faso, trials of participatory community-based selection of indigents have
      been effective. However, the process for selecting indigents in urban areas is
      not yet clear. METHODS: This study evaluates a community-funded participatory
      indigent selection process in both a formal (loti) and an informal (non-loti)
      neighbourhood in the urban setting of Burkina Faso's capital. This was an
      exploratory study to evaluate the processes and effectiveness of participatory
      targeting. We conducted individual interviews (n = 26) and analyzed secondary
      qualitative data (eight focus groups, 16 individual interviews). We also used the
      results of a socioeconomic survey (carried out by the Ouaga HDSS in 2011) of all
      the households established in the areas, including those of selected indigents.
      RESULTS: The coverage of indigent targeting was very low: 0.33% (loti) and 0.22%
      (non loti). In the non loti neighbourhood, the level of poverty among people
      selected was higher than the mean level of the poor who were not selected. Some
      indigents selected in the loti neighbourhood were not among the worst-off. The
      process was difficult to organize in the loti neighbourhood; people knew each
      other less well and were not very available, and there were cases of collusion.
      The process worked well in the non loti neighbourhood. CONCLUSIONS: This
      intervention research provides new evidence about the feasibility of a community
      based selection process in an urban setting in Africa by comparing two different
      urban settings. The participatory community-based selection process appeared to
      be suitable for the non loti neighbourhood, but other targeting strategies need
      to be found for loti areas. Specific budgets need to be allocated to increase the
      coverage of indigent targeting.

PMID- 24739442
TI  - The evolution of laryngeal reinnervation, the current state of science and
      thoughts for future treatments.
AB  - The treatment of unilateral vocal fold palsy (UVFP) or bilateral vocal fold palsy
      (BVFP) has been the subject of debate and experiment for 150 years. To date,
      dozens of different surgical methods have been described to reinnervate this most
      complex of organs, the larynx. As yet, there is no consensus on the most
      functionally effective method of reinnervation. However, it is a rapidly
      expanding area of research and remains an area of controversy. Indications for
      reinnervation for both UVFP and BVFP are still evolving and our understanding of
      the neuromuscular supply to the larynx continues to expand. What may have been
      considered unacceptable results from previous studies with one pathology may
      actually be of benefit in patients with different pathologies. This uncertainty
      of treatment options and potential outcomes can be confusing. In addition
      alternative techniques have been postulated as mainstays or adjuncts of treatment
      to the stalwart of reinnervation, neurorrhaphy. Determining what the correct
      treatment for an individual patient should be is still a gray area. With this in
      mind, this article reviews the evolution of laryngeal reinnervation, reviews the
      current state of the science, and suggests directions in which it might move in
      the future. 

PMID- 24739443
TI  - Types and timing of therapy for vocal fold paresis/paralysis after thyroidectomy:
      a systematic review and meta-analysis.
AB  - OBJECTIVES: To perform a systematic literature review to evaluate the type and
      timing of therapy for vocal fold paresis/paralysis after thyroidectomy and
      develop a primary decision-making pathway. STUDY DESIGN: Meta-analysis. METHODS:
      Four databases and one journal were searched using the key words of
      "thyroidectomy," "vocal cord paresis/paralysis," and "therapy." Study quality was
      evaluated using the Cochrane Collaboration's risk of bias tools. Data regarding
      type and timing of therapy were extracted from 39 articles. Odds ratios (ORs),
      relative risk (RR), 95% confidence interval, and heterogeneity were recorded.
      Logistic regression analysis was performed to determine the relationships between
      timing and OR/RR. RESULTS: Among the 13 studies investigating unilateral
      paresis/paralysis, five focused on early therapy (0-6 months). In these studies,
      the OR for clinical heterogeneity was significantly higher after neurolysis than
      after injection laryngoplasty and voice training (Q = 17.002, I(2) = 78%, P =
      0.000), and the RR for heterogeneity was significantly higher after injection
      laryngoplasty at >=12 months than <12 months (Q = 9.984, I(2) = 89.9%, P =
      0.002). In the 26 studies that investigated bilateral paresis/paralysis, the OR
      for heterogeneity was significantly higher for bilateral posterior cordectomy
      than for endolaryngeal laterofixation (Q = 3.510, I(2) = 71.5%, P = 0.061) and
      laser arytenoidectomy with posterior cordectomy (Q = 2.90, I(2) = 65.6%, P =
      0.088). CONCLUSIONS: For unilateral vocal fold paresis/paralysis after
      thyroidectomy, we recommend absorbable mass injection laryngoplasty, voice
      training, and neurolysis during the first 12 months but laryngeal reinnervation
      after 12 months. For bilateral vocal fold paresis/paralysis, we recommend early
      laterofixation and combined laser arytenoidectomy with posterior cordectomy after
      12 months.

PMID- 24739444
TI  - Assessment of patient experience with unilateral vocal fold immobility: a
      preliminary study.
AB  - OBJECTIVE: Systematically moving toward patient-centered care for unilateral
      vocal fold immobility (UVFI) requires comprehensive understanding of the
      variability of actual patient experiences. This rigorous qualitative study
      assesses UVFI-related disability and proposes a preliminary taxonomy of UVFI
      patient experience. STUDY DESIGN: (1) Semistructured interviews and (2) taxonomy
      development. METHODS: Consecutive UVFI patients presenting July to September,
      2012, prospectively underwent open-ended interviews investigating how UVFI
      affected their quality of life (QOL) and had caused disability. Comments reported
      by >20% were synthesized into axes based on content similarity. Variables were
      arranged into a preliminary taxonomy of UVFI patient experience, which was
      evaluated for four attributes of face validity. RESULTS: The majority of 39
      patients had "extensive" baseline voice use (56%) and an iatrogenic etiology
      (62%). Taxonomy of patient experience included three main axes of symptomatic
      classification: (1) voice, (2) swallowing, and (3) breathing-all with intrinsic
      (physical and emotional) and extrinsic (social) subaxes that describe major
      impacts on QOL. Voice complaints were 100% penetrant, whereas breathing and
      swallowing symptoms afflicted 76% and 66%, respectively, of interviewees. Of
      affected patients, solid and liquid dysphagia was experienced by 70% and 63%,
      respectively. Of dyspneic patients, shortness of breath existed with talking
      (97%) and exercise (72%). Persistent throat congestion (76%), weakened cough
      (62%), globus (62%), and dysfunctional valsalva (41%) were frequent. CONCLUSIONS:
      Patient experience with UVFI has been incompletely characterized. This
      qualitative assessment and preliminary taxonomy highlight several related patient
      experiences not well documented in the literature or incorporated into currently
      available metrics.

PMID- 24739445
TI  - Changes in biomarkers in HIV-1-infected treatment-naive patients treated with
      tenofovir DF/emtricitabine plus atazanavir/ritonavir or lopinavir/ritonavir for
      96 weeks: the CASTLE biomarker substudy.
AB  - BACKGROUND: The impact of boosted protease inhibitor therapy on inflammatory and
      cardiovascular biomarker levels in treatment-naive HIV-infected patients remains
      unclear and may differ between agents. Unconjugated bilirubin elevation, which
      favourably affects vascular biomarkers and cardiovascular disease risk in
      Gilbert's syndrome, occurs with atazanavir. METHODS: CASTLE was a 96-week study
      comparing efficacy and safety in treatment-naive HIV-1-infected patients
      randomized to atazanavir/ritonavir (ATV/r) versus lopinavir/ritonavir (LPV/r),
      each in combination with tenofovir disoproxil fumarate/emtricitabine. In this
      substudy, fasting plasma tumour necrosis factor-alpha (TNF-alpha), interleukin-6
      (IL-6), high sensitivity C-reactive protein (hs-CRP), plasminogen activator
      inhibitor-1 (PAI-1) and fibrinogen were assessed at baseline, week 12, 24, 48 and
      96. Impact of grade 3-4 hyperbilirubinaemia on biomarkers was examined. RESULTS:
      CASTLE demonstrated similar efficacy in both treatment arms with higher rates of
      hyperbilirubinaemia on ATV/r and elevated lipids on LPV/r. In this substudy
      (n=224), patterns of biomarker expression were similar between the ATV/r and
      LPV/r groups and between-group differences in biomarker percentage change from
      baseline were not significant at 48 and/or 96 weeks. Hyperbilirubinaemia did not
      influence fasting biomarker expression. CONCLUSIONS: No significant differences
      were noted between ATV/r and LPV/r for biomarker percentage changes from
      baseline. Furthermore, no association was found between total bilirubin levels
      and biomarker expression.

PMID- 24739446
TI  - Methods for measuring, enhancing, and accounting for medication adherence in
      clinical trials.
AB  - Adherence to rationally prescribed medications is essential for effective
      pharmacotherapy. However, widely variable adherence to protocol-specified dosing
      regimens is prevalent among participants in ambulatory drug trials, mostly
      manifested in the form of underdosing. Drug actions are inherently dose and time
      dependent, and as a result, variable underdosing diminishes the actions of trial
      medications by various degrees. The ensuing combination of increased variability
      and decreased magnitude of trial drug actions reduces statistical power to
      discern between-group differences in drug actions. Variable underdosing has many
      adverse consequences, some of which can be mitigated by the combination of
      reliable measurements of ambulatory patients' adherence to trial and nontrial
      medications, measurement-guided management of adherence, statistically and
      pharmacometrically sound analyses, and modifications in trial design. Although
      nonadherence is prevalent across all therapeutic areas in which the patients are
      responsible for treatment administration, the significance of the adverse
      consequences depends on the characteristics of both the disease and the
      medications. 

PMID- 24739447
TI  - Response to "the effect of green tea with exceptionally high catechin content on
      nadolol plasma concentration".

PMID- 24739448
TI  - Have antiepileptic drug prescription claims changed following the FDA suicidality
      warning? An evaluation in a state Medicaid program.
AB  - OBJECTIVE: In January 2008, the Food and Drug Administration (FDA) communicated
      concerns and, in May 2009, issued a warning about an increased risk of
      suicidality for all antiepileptic drugs (AEDs). This research evaluated the
      association between the FDA suicidality communications and the AED prescription
      claims among members with epilepsy and/or psychiatric disorder. METHODS: A
      longitudinal interrupted time-series design was utilized to evaluate Oklahoma
      Medicaid claims data from January 2006 through December 2009. The study included
      9289 continuously eligible members with prevalent diagnoses of epilepsy and/or
      psychiatric disorder and at least one AED prescription claim. Trends, expressed
      as monthly changes in the log odds of AED prescription claims, were compared
      across three time periods: before (January 2006 to January 2008), during
      (February 2008 to May 2009), and after (June 2009 to December 2009) the FDA
      warning. RESULTS: Before the FDA warning period, a significant upward trend of
      AED prescription claims of 0.01% per month (99% CI: 0.008% to 0.013%, p<0.0001)
      was estimated. In comparison to the prewarning period, no significant change in
      trend was detected during (-20.0%, 99% CI: -70.0% to 30.0%, p=0.34) or after
      (80.0%, 99% CI: -20.0% to 200.0%, p=0.03) the FDA warning period. After
      stratification, no diagnostic group (i.e., epilepsy alone, epilepsy and comorbid
      psychiatric disorder, and psychiatric disorder alone) experienced a significant
      change in trend during the entire study period (p>0.01). CONCLUSIONS: During the
      time period considered, the FDA AED-related suicidality warning does not appear
      to have significantly affected prescription claims of AED medications for the
      study population.

PMID- 24739449
TI  - Safety of tianeptine use in patients with epilepsy.
AB  - Depression is a frequent comorbidity in patients with epilepsy (PWE). However, it
      is often undertreated because of concerns of seizure exacerbation by
      antidepressant treatment. The effect of tianeptine on seizure frequency is not
      known as yet. Thus, we aimed to evaluate the influence of tianeptine on the
      seizure frequency in PWE. We retrospectively reviewed the medical records of PWE
      who received tianeptine between January 2006 and June 2013 at the Epilepsy Center
      of Seoul National University Hospital. Patients were excluded if the dose or type
      of antiepileptic drugs (AEDs) they took was altered at the start of tianeptine
      treatment or if the treatment period of tianeptine was <3 months. A total of 74
      PWE were enrolled in our study (male: 32, mean age: 41.9+/-14.5). Sixty-nine
      patients had localization-related epilepsy, and 5 had idiopathic generalized
      epilepsy (IGE). Mean seizure frequency during the 3-month period just after
      tianeptine exposure was compared with the baseline seizure frequency, which
      showed no change in 69 (93.2%) patients, decrease in 2 (2.7%) patients, and
      increase in 3 patients (4.1%). The type of epileptic syndrome, the baseline
      seizure frequency, and the number of coadministered AEDs did not influence the
      change in seizure frequency after tianeptine prescription. Change in seizure
      frequency did not differ between the patients given tianeptine as an additive
      antidepressant and those given tianeptine as a replacement antidepressant. Our
      data suggest that tianeptine can be prescribed safely to PWE with depression
      without increasing the seizure frequency regardless of the baseline severity of
      epilepsy. Tianeptine may be actively considered as a first-choice antidepressant
      or as an alternative antidepressant in PWE with depression.

PMID- 24739450
TI  - Patient perceptions of the referral of older adults to an epilepsy clinic: do
      patients and professionals agree who should be referred to a specialist?
AB  - The aim of this study was to establish whether older patients concurred with
      previously reported staff perceptions of why older adults may be underrepresented
      in epilepsy clinics. Fifteen interviews with older patients provided support for
      four of seven key factors previously suggested by professionals as leading to
      underreferral of older adults: unclear referral pathway, complex differential
      diagnosis, gaps in referrer knowledge, and the length of time since onset.
      However, the patients interviewed did not report that patient difficulties
      accessing the hospital, patient reluctance to attend clinics, or the particular
      characteristics of older patients (knowledge, awareness, and willingness to ask
      for help) made it less likely that older adults would want to attend a specialist
      epilepsy clinic. While recognizing the limitations of the study, particularly in
      relation to the number of participants, we believe that it provides valuable
      further insights into the age-bias apparent in referral patterns to specialist
      epilepsy services. Of particular concern are professional assumptions regarding
      older patients' willingness to attend appointments and about the impact of
      seizures on the life of an older adult. 

PMID- 24739452
TI  - Effectiveness of a complex intervention in reducing the prevalence of smoking
      among adolescents: study design of a cluster-randomized controlled trial.
AB  - BACKGROUND: The likelihood of an adolescent taking up smoking may be influenced
      by his or her society, school and family. Thus, changes in the immediate
      environment may alter a young person's perception of smoking. METHODS/DESIGN: The
      proposed multi-center, cluster-randomized controlled trial will be stratified by
      the baseline prevalence of smoking in schools. Municipalities with fewer than
      100,000 inhabitants will be randomly assigned to a control or intervention group.
      One secondary school will be randomly selected from each municipality. These
      schools will be randomized to two groups: the students of one will receive any
      existing educational course regarding smoking, while those of the other school
      will receive a four-year, class-based curriculum intervention (22 classroom
      lessons) aimed at reinforcing a smoke-free school policy and encouraging smoking
      cessation in parents, pupils, and teachers. The intervention will also include
      annual meetings with parents and efforts to empower adolescents to change the
      smoking-related attitudes and behaviors in their homes, classrooms and
      communities.We will enroll children aged 12-13 years as they enter secondary
      school during two consecutive school years (to obtain sufficient enrolled
      subjects). We will follow them for five years, until two years after they leave
      secondary school. All external evaluators and analysts will be blinded to school
      allocation.The aim of this study is to analyze the effectiveness of a complex
      intervention in reducing the prevalence of smoking in the third year of
      compulsory secondary education (ESO) and two years after secondary school, when
      the participants are 14-15 and 17-18 years old, respectively. DISCUSSION: Most
      interventions aimed at preventing smoking among adolescents yield little to no
      positive long-term effects. This clinical trial will analyze the effectiveness of
      a complex intervention aimed at reducing the incidence and prevalence of smoking
      in this vulnerable age group. TRIAL REGISTRATION: Current Controlled Trials:
      NCT01602796.

PMID- 24739453
TI  - The future of reproductive medical education.

PMID- 24739454
TI  - Preterm births, multiples, and fertility treatment: recommendations for changes
      to policy and clinical practices.

PMID- 24739455
TI  - Is it about business, education, or patient care?

PMID- 24739456
TI  - Is it useful to combine sputum cytology and low-dose spiral computed tomography
      for early detection of lung cancer in formerly asbestos-exposed power industry
      workers?
AB  - BACKGROUND: Low-dose spiral computed tomography (LDSCT) in comparison to
      conventional chest X-ray proved to be a highly sensitive method of diagnosing
      early stage lung cancer. However, centrally located early stage lung tumours
      remain a diagnostic challenge. We determined the practicability and efficacy of
      early detection of lung cancer when combining LDSCT and sputum cytology. METHODS:
      Of a cohort of 4446 formerly asbestos exposed power industry workers, we examined
      a subgroup of 187 (4.2%) high risk participants for lung cancer at least once
      with both LDSCT and sputum cytology. After the examination period the
      participants were followed-up for more than three years. RESULTS: The
      examinations resulted in the diagnosis of lung cancer in 12 participants (6.4%).
      Six were in clinical stage I. We found 10 non-small cell lung carcinomas and one
      small cell lung carcinoma. Sputum specimens showed suspicious pathological
      findings in seven cases and in 11 cases the results of LDSCT indicated
      malignancies. The overall sensitivity and specificity of sputum cytology was
      58.0% and 98% with positive (PPV) and negative (NPV) predictive values of 70% and
      97%. For LDSCT we calculated the sensitivity and specificity of 92% and 97%. The
      PPV and NPV were 65% and 99% respectively. CONCLUSIONS: Our results confirmed
      that in surveillance programmes a combination of sputum cytology and LDSCT is
      well feasible and accepted by the participants. Sputum examination alone is not
      effective enough for the detection of lung cancer, especially at early stage.
      Even in well- defined risk groups highly exposed to asbestos, we cannot recommend
      the use of combined LDSCT and sputum cytology examinations as long as no survival
      benefit has been proved for the combination of both methods. For ensuring low
      rates of false-positive and false-negative results, programme planners must
      closely cooperate with experienced medical practitioners and pathologists in a
      well-functioning interdisciplinary network.

PMID- 24739457
TI  - Ozurdex((r)) reduces the retinal thickness in radiation maculopathy refractory to
      bevacizumab.

PMID- 24739458
TI  - Kikuchi-Fujimoto's disease associated with systemic lupus erythematous: difficult
      case report and literature review.
AB  - Kikuchi-Fujimoto's disease (KFD), or histiocytic necrotizing lymphadenitis, is a
      benign and self-limiting disease of unknown aetiology. KFD tends to affect a
      young population under 30 years of age and predominantly females. KFD is a rare
      pathology and its association with systemic lupus erythematosus (SLE) is not
      frequent. Herein, we present the case of a male Italian patient with SLE in
      association with KFD with 5 years of follow-up, where a differential diagnosis
      from infection or lymphoproliferative disease was problematic. 

PMID- 24739460
TI  - The preparation of porcine circovirus type 2 (PCV2) virus-like particles using a
      recombinant pseudorabies virus and its application to vaccine development.
AB  - Porcine circovirus type 2 (PCV2) is the primary causative agent of an
      economically important swine disease, now known as porcine-associated disease
      (PCVAD). The only structural protein of viral capsid, Cap has become the major
      target for development of PCV2 subunit vaccines. The purpose of this study is to
      express Cap of PCV2 using a recombinant pseudorabies virus (PRV) that is gE gene
      deficient, which is a widely used PRV marker vaccine. The recombinant PRV, gE(
      )/PCV2cap(+)PRV, was constructed using homologous recombination techniques, in
      order to replace the upstream of the gE gene with the PCV2 cap gene. The
      expression of Cap during virus replication was confirmed using immunofluorescence
      and Western blotting analysis. The expressed Cap protein self-assembled into
      virus-like particles (VLPs), which was demonstrated using electromicrography. The
      immunization of mice or guinea pigs with purified VLPs could induce significant,
      specific antibody responses to PCV2 Cap. These results demonstrate an alternative
      to PCV2 for the development of a VLP-based subunit vaccine. 

PMID- 24739461
TI  - The benefits, risks, and efficacy of strabismus surgery in adults.
AB  - Strabismus surgery in adults achieves satisfactory alignment with one operation
      in approximately 80% of patients, depending on the specific nature of the
      problem. Risks of adult strabismus surgery are relatively low, and serious
      complications are anecdotal and rare. Even if the strabismus has been long
      standing, most adults will experience some improvement in binocular function
      after strabismus surgery. Consequently, adult strabismus surgery should not be
      considered merely cosmetic in most cases. In esotropic patients, this improvement
      typically takes the form of an expansion of binocular visual fields; however,
      some patients may also regain stereopsis. There are many psychosocial benefits to
      adult strabismus surgery. This is reflected in the finding that the majority of
      adults surveyed with strabismus would trade a portion of their life expectancy to
      be rid of their strabismus. 

PMID- 24739459
TI  - A deep survey of alternative splicing in grape reveals changes in the splicing
      machinery related to tissue, stress condition and genotype.
AB  - BACKGROUND: Alternative splicing (AS) significantly enhances transcriptome
      complexity. It is differentially regulated in a wide variety of cell types and
      plays a role in several cellular processes. Here we describe a detailed survey of
      alternative splicing in grape based on 124 SOLiD RNAseq analyses from different
      tissues, stress conditions and genotypes. RESULTS: We used the RNAseq data to
      update the existing grape gene prediction with 2,258 new coding genes and 3,336
      putative long non-coding RNAs. Several gene structures have been improved and
      alternative splicing was described for about 30% of the genes. A link between AS
      and miRNAs was shown in 139 genes where we found that AS affects the miRNA target
      site. A quantitative analysis of the isoforms indicated that most of the spliced
      genes have one major isoform and tend to simultaneously co-express a low number
      of isoforms, typically two, with intron retention being the most frequent
      alternative splicing event. CONCLUSIONS: As described in Arabidopsis, also grape
      displays a marked AS tissue-specificity, while stress conditions produce splicing
      changes to a minor extent. Surprisingly, some distinctive splicing features were
      also observed between genotypes. This was further supported by the observation
      that the panel of Serine/Arginine-rich splicing factors show a few, but very
      marked differences between genotypes. The finding that a part the splicing
      machinery can change in closely related organisms can lead to some interesting
      hypotheses for evolutionary adaptation, that could be particularly relevant in
      the response to sudden and strong selective pressures.

PMID- 24739462
TI  - IKKalpha restoration via EZH2 suppression induces nasopharyngeal carcinoma
      differentiation.
AB  - Lack of cellular differentiation is a key feature of nasopharyngeal carcinoma
      (NPC), but it also presents as a unique opportunity for intervention by
      differentiation therapy. Here using RNA-seq profiling analysis and functional
      assays, we demonstrate that reduced IKKalpha expression is responsible for the
      undifferentiated phenotype of NPC. Conversely, overexpression of IKKalpha induces
      differentiation and reduces tumorigenicity of NPC cells without activating NF
      kappaB signalling. Importantly, we describe a mechanism whereby EZH2 directs
      IKKalpha transcriptional repression via H3K27 histone methylation on the IKKalpha
      promoter. The differentiation agent, retinoic acid, increases IKKalpha expression
      by suppressing EZH2-mediated H3K27 histone methylation, resulting in enhanced
      differentiation of NPC cells. In agreement, an inverse correlation between
      IKKalpha (low) and EZH2 (high) expression is associated with a lack of
      differentiation in NPC patient samples. Collectively, these findings demonstrate
      a role for IKKalpha in NPC differentiation and reveal an epigenetic mechanism for
      IKKalpha regulation, unveiling a new avenue for differentiation therapy. 

PMID- 24739463
TI  - Improving recruitment in pediatric clinical research: a strategy to consider.

PMID- 24739464
TI  - Obtaining informed consent in pediatric clinical trials.

PMID- 24739465
TI  - Disease prevalence based on older people's self-reports increased, but patient
      general practitioner agreement remained stable, 1992-2009.
AB  - OBJECTIVES: Previous studies revealed increases in the prevalence of chronic
      diseases in older people in most countries. This study investigated if a changed
      inclination to report diseases underlies these increases, by comparing the
      agreement between self-reports and general practitioner (GP) records of chronic
      diseases between 1992-1993 and 2008-2009. STUDY DESIGN AND SETTINGS: Cross
      sectional analyses were performed on data from two waves of the Longitudinal
      Aging Study Amsterdam. Data from older adults aged 60-85 years came from 1992
      1993 (N=1,896) and from the same age group in 2008-2009 (N=1,086). We compared
      respondent (R) and GP records of lung disease, cardiac disease, peripheral
      arterial disease, stroke, diabetes, arthritis, and cancer. Multilevel regression
      models were applied to examine (change in) predictors of over-reporting (R+, GP-)
      and under-reporting (R-, GP+). RESULTS: Over-reporting of chronic diseases became
      significantly more common over time, whereas under-reporting became less common.
      Agreement and change in agreement differed across the specific diseases. Under
      reporting was associated with male gender; over-reporting with female gender,
      worse self-rated health, and worse physical functioning. Older adults were less
      accurate in their self-reports than younger adults. CONCLUSION: Trends in self
      reported chronic diseases may be influenced by changes in reporting behavior, and
      future studies should take this possibility into account.

PMID- 24739466
TI  - Reliability of small biopsy or cytology for the diagnosis of pulmonary mucinous
      adenocarcinoma.
AB  - AIM: In case of mucinous adenocarcinoma (MA), cytologic atypia is usually mild to
      moderate, or may be absent in some cases, incurring a diagnostic pitfall in
      recognising MA in small tissue biopsy and cytology specimens. The purpose of this
      study was to evaluate the diagnostic accuracy of transthoracic fine needle
      aspiration (FNA) or core needle biopsy (CNB) for making a diagnosis of pulmonary
      MA. METHODS: We retrospectively reviewed a consecutive series of 185 patients who
      underwent curative operation for MA. Among those patients, 105 patients underwent
      preoperative percutaneous FNA (n=34) or CNB (n=79). Eight patients underwent FNA
      and CNB for the same tumour. Diagnostic accuracies of FNA and CNB for making a
      diagnosis of MA were evaluated, and the contribution of various clinicopathologic
      parameters to subtyping accuracy was analysed. RESULTS: Diagnostic accuracies of
      FNA and CNB in determining malignancy were 67.6% and 87.3%, respectively, and
      those for making a diagnosis of MA were 20.6% and 59.5%, respectively. Univariate
      analysis indicated that the type of biopsy procedure and prominent growth pattern
      of MA are significant factors for successful histologic diagnosis. Tumour nature
      on CT and the length of biopsy specimen were not related to successful diagnosis
      of histology subtyping of MA. CONCLUSIONS: CNB appears to be feasible and
      accurate for diagnosing a MA. Prominent growth patterns of MA are significant
      factors for successful histologic diagnosis of MA.

PMID- 24739467
TI  - Haemophilus influenzae porine ompP2 gene transfer mediated by graphene oxide
      nanoparticles with effects on transformation process and virulence bacterial
      capacity.
AB  - BACKGROUND: H. influenzae is a natural competent bacterium that can uptake DNA
      from the environment and recombine into bacterial genome. The outbreaks of
      Brazilian purpuric fever, heavily polluted areas of a different H. influenzae
      biogroup - aegyptius - as well as gene transference between Neisseria meningitis
      make the transformation process an important evolutionary factor. This work
      studied the horizontal transference of the ompP2 gene from a multiresistant
      strain of H. influenzae 07 (NTHi), under the influence of graphene oxide
      nanoparticles in order to mimic an atmosphere rich in suspended particles and
      this way verify if the CFU transformants number was increased. MATERIAL AND
      METHODS: In this article the gene ompP2 was transformed into different strains of
      H. influenzae mediated or not by graphene oxide nanoparticles in suspension,
      followed by the adhesion tests in Hec-1B (human endometrium adenocarcinoma) and
      A549 (pulmonary epithelial carcinoma) cells lines. The transformation frequency
      and the adhesion capacity were determined in all the mutants to which the ompP2
      gene was transferred and compared to their wild type strains. RESULTS: The
      nanoparticles increased the transformation ratio of one particular strain
      isolated from a pneumonia case. The adhesion patterns to A549 and Hec1b cell
      lines of these mutated bacteria has their capacity increased when compared to the
      wild type. CONCLUSIONS: Graphene oxide nanoparticles aid the transformation
      process, helping to increase the number of CFUs, and the mutants generated with
      the ompP2 gene from a H. influenzae resistant strain not only present a
      chloramphenicol resistance but also have an increased adherence patterns in A549
      and Hec1B cell lines.

PMID- 24739468
TI  - Detection and molecular analysis of Campylobacter ureolyticus in domestic
      animals.
AB  - Previous studies showed the presence of Campylobacter ureolyticus in a large
      proportion of diarrhoeal samples from patients in Ireland. This emerging
      gastrointestinal pathogen was the second most common Campylobacter species
      detected in patients presenting with gastroenteritis, surpassed only by C.
      jejuni. However, the source of C. ureolyticus infections in humans remains
      unknown. The aim of this study was to investigate the presence of C. ureolyticus
      in a range of domestic animals. Over a period of 6 months, 164 samples collected
      from various domestic animals were tested using molecular method based on
      detection of the C. ureolyticus specific hsp60 gene. These included canine faeces
      (n = 44), feline faeces (n = 31) and porcine faeces (n = 89). C. ureolyticus was
      detected in 32% (10/31) of feline faeces, 9% (4/44) of canine faeces and 18%
      (16/89) of porcine faeces. Random Amplified Polymorphic DNA (RAPD) analysis of C.
      ureolyticus isolates showed that an isolate from a cat is genetically similar to
      a strain isolated from a patient presenting with gastroenteritis. This study
      reports the first detection and isolation of this organism in domestic animals in
      Ireland, with a potential source for human infection. Together with the
      previously reported detection of C. ureolyticus in bovine samples, it is likely
      that this emerging pathogen has a zoonotic potential. 

PMID- 24739469
TI  - Silver nanoparticle/bacterial cellulose gel membranes for antibacterial wound
      dressing: investigation in vitro and in vivo.
AB  - Bacterial cellulose (BC) has attracted increasing attention as a novel wound
      dressing material, but its antimicrobial activity, which is one of the critical
      skin-barrier functions in wound healing, is not sufficient for use in practical
      applications. To overcome such a deficiency, silver nanoparticles were generated
      and self-assembled on the surface of BC nanofibers, forming a stable and evenly
      distributed Ag nanoparticle coated BC nanofiber (AgNP-BC). The performance of
      AgNP-BC was systematically studied in terms of antibacterial activities,
      cytocompatibility and effects on wound healing. The results showed that AgNP-BC
      exhibited significant antibacterial activity against Staphylococcus aureus.
      Moreover, AgNP-BC allowed attachment, and growth of rat fibroblasts with low
      cytotoxicity emerged. Based on these advantages, AgNP-BC samples were applied in
      a second-degree rat wound model. Wound flora showed a significant reduction
      during the healing. The fresh epidermal and dermis thicknesses with AgNP-BC
      samples were 111 and 855 um respectively, higher than 74 and 619 um for BC groups
      and 57 and 473 um for untreated control wounds. The results demonstrated that
      AgNP-BC could reduce inflammation and promote scald wound healing.

PMID- 24739470
TI  - Regulation of senescence under elevated atmospheric CO2 via ubiquitin
      modification.
AB  - Elevated atmospheric CO2 concentration is a serious global environmental problem.
      Elevated CO2 affects plant growth by changing primary metabolism, closely related
      to carbon (C) and nitrogen (N) availability. Under sufficient N conditions, plant
      growth is dramatically promoted by elevated CO2. When N availability is limited,
      however, elevated CO2 disrupts the balance between cellular C and N (C/N).
      Disruption of the C/N balance is regarded as an important factor in plant growth
      defects. Here we highlight the regulation of senescence in higher plants by
      atmospheric CO2 and N, and the physiological function of C/N-related ubiquitin
      ligase ATL31 under condition of elevated CO2. We also provide an overview of the
      ubiquitin ligases and related enzymes involved in regulating senescence in
      plants.

PMID- 24739471
TI  - Effectiveness and cost-effectiveness of ehealth interventions in somatic
      diseases: a systematic review of systematic reviews and meta-analyses.
AB  - BACKGROUND: eHealth potentially enhances quality of care and may reduce health
      care costs. However, a review of systematic reviews published in 2010 concluded
      that high-quality evidence on the benefits of eHealth interventions was still
      lacking. OBJECTIVE: We conducted a systematic review of systematic reviews and
      meta-analyses on the effectiveness/cost-effectiveness of eHealth interventions in
      patients with somatic diseases to analyze whether, and to what possible extent,
      the outcome of recent research supports or differs from previous conclusions.
      METHODS: Literature searches were performed in PubMed, EMBASE, The Cochrane
      Library, and Scopus for systematic reviews and meta-analyses on eHealth
      interventions published between August 2009 and December 2012. Articles were
      screened for relevance based on preset inclusion and exclusion criteria.
      Citations of residual articles were screened for additional literature. Included
      papers were critically appraised using the Preferred Reporting Items for
      Systematic Reviews and Meta-Analyses (PRISMA) Statement before data were
      extracted. Based on conclusions drawn by the authors of the included articles,
      reviews and meta-analyses were divided into 1 of 3 groups: suitable, promising,
      or limited evidence on effectiveness/cost-effectiveness. Cases of uncertainty
      were resolved by consensus discussion. Effect sizes were extracted from papers
      that included a meta-analysis. To compare our results with previous findings, a
      trend analysis was performed. RESULTS: Our literature searches yielded 31
      eligible reviews, of which 20 (65%) reported on costs. Seven papers (23%)
      concluded that eHealth is effective/cost-effective, 13 (42%) underlined that
      evidence is promising, and others found limited or inconsistent proof.
      Methodological quality of the included reviews and meta-analyses was generally
      considered high. Trend analysis showed a considerable accumulation of literature
      on eHealth. However, a similar percentage of papers concluded that eHealth is
      effective/cost-effective or evidence is at least promising (65% vs 62%). Reviews
      focusing primarily on children or family caregivers still remained scarce.
      Although a pooled (subgroup) analysis of aggregate data from randomized studies
      was performed in a higher percentage of more recently published reviews (45% vs
      27%), data on economic outcome measures were less frequently reported (65% vs
      85%). CONCLUSIONS: The number of reviews and meta-analyses on eHealth
      interventions in patients with somatic diseases has increased considerably in
      recent years. Most articles show eHealth is effective/cost-effective or at least
      suggest evidence is promising, which is consistent with previous findings.
      Although many researchers advocate larger, well-designed, controlled studies, we
      believe attention should be given to the development and evaluation of strategies
      to implement effective/cost-effective eHealth initiatives in daily practice,
      rather than to further strengthen current evidence.

PMID- 24739473
TI  - Contribution of obstetrics and gynecology societies in East, Central, and
      Southern Africa to the prevention of unsafe abortion in the region.
AB  - Maternal mortality and morbidity rates are very high in Africa. A large
      proportion of these deaths is attributed to unsafe abortion. The International
      Federation of Gynecology and Obstetrics, in collaboration with its member
      societies in each participating country, their respective Ministries of Health,
      and various non-governmental agencies, has developed an initiative to prevent
      unsafe abortion and the morbidity and mortality attributed to it. Over the past 5
      years, these teams undertook situational analyses, and developed and implemented
      plans of action. The progress achieved in this region is described in this
      article.

PMID- 24739472
TI  - Cost savings of reduced constipation rates attributed to increased dietary fiber
      intakes: a decision-analytic model.
AB  - BACKGROUND: Nearly five percent of Americans suffer from functional constipation,
      many of whom may benefit from increasing dietary fiber consumption. The annual
      constipation-related healthcare cost savings associated with increasing intakes
      may be considerable but have not been examined previously. The objective of the
      present study was to estimate the economic impact of increased dietary fiber
      consumption on direct medical costs associated with constipation. METHODS:
      Literature searches were conducted to identify nationally representative input
      parameters for the U.S. population, which included prevalence of functional
      constipation; current dietary fiber intakes; proportion of the population meeting
      recommended intakes; and the percentage that would be expected to respond, in
      terms of alleviation of constipation, to a change in dietary fiber consumption. A
      dose-response analysis of published data was conducted to estimate the percent
      reduction in constipation prevalence per 1 g/day increase in dietary fiber
      intake. Annual direct medical costs for constipation were derived from the
      literature and updated to U.S. $ 2012. Sensitivity analyses explored the impact
      on adult vs. pediatric populations and the robustness of the model to each input
      parameter. RESULTS: The base case direct medical cost-savings was $12.7 billion
      annually among adults. The base case assumed that 3% of men and 6% of women
      currently met recommended dietary fiber intakes; each 1 g/day increase in dietary
      fiber intake would lead to a reduction of 1.9% in constipation prevalence; and
      all adults would increase their dietary fiber intake to recommended levels (mean
      increase of 9 g/day). Sensitivity analyses, which explored numerous alternatives,
      found that even if only 50% of the adult population increased dietary fiber
      intake by 3 g/day, annual medical costs savings exceeded $2 billion. All
      plausible scenarios resulted in cost savings of at least $1 billion. CONCLUSIONS:
      Increasing dietary fiber consumption is associated with considerable cost
      savings, potentially exceeding $12 billion, which is a conservative estimate
      given the exclusion of lost productivity costs in the model. The finding that
      $12.7 billion in direct medical costs of constipation could be averted through
      simple, realistic changes in dietary practices is promising and highlights the
      need for strategies to increase dietary fiber intakes.

PMID- 24739474
TI  - Increase in preference for female obstetricians and gynecologists in job
      advertisements in Turkey.

PMID- 24739475
TI  - A single-visit approach to cervical cancer prevention in rural Thailand.

PMID- 24739476
TI  - Contraception following abortion and the treatment of incomplete abortion.
AB  - Family planning counseling and the provision of postabortion contraception should
      be an integrated part of abortion and postabortion care to help women avoid
      another unplanned pregnancy and a repeat abortion. Postabortion contraception is
      significantly more effective in preventing repeat unintended pregnancy and
      abortion when it is provided before women leave the healthcare facility where
      they received abortion care, and when the chosen method is a long-acting
      reversible contraceptive (LARC) method. This article provides evidence supporting
      these two critical aspects of postabortion contraception. It suggests that
      gynecologists and obstetricians have an ethical obligation to do everything
      necessary to ensure that postabortion contraception, with a focus on LARC
      methods, becomes an integral part of abortion and postabortion care, in line with
      the recommendations of the International Federation of Gynecology and Obstetrics
      and of several other organizations. 

PMID- 24739477
TI  - Evaluation of healthcare professionals' understanding of eponymous maneuvers and
      mnemonics in emergency obstetric care provision.
AB  - OBJECTIVE: To evaluate whether eponymous maneuvers and mnemonics taught for the
      management of shoulder dystocia, vaginal breech delivery, and uterine inversion
      were remembered and understood in practice. METHODS: A questionnaire was
      distributed to obstetricians and midwives collecting information about the
      HELPERR and PALE SISTER mnemonics. Three extended matching questions evaluated
      participants' knowledge of the correct maneuvers, with their matching eponyms,
      used in the management of shoulder dystocia, vaginal breech delivery, and uterine
      inversion. RESULTS: Of the 112 participants, 90% were familiar with the HELPERR
      mnemonic, with 79% using it in their practice. Of those who used it, only 32%
      could correctly decipher it (P = 0.032). PALE SISTER was mostly unfamiliar. The
      percentages of correct maneuvers used for managing shoulder dystocia, breech
      delivery, and uterine inversion were 84.6%, 58.3%, and 28.6%, respectively.
      However, the eponyms were correctly matched to their maneuvers in only 33.3%,
      14.3%, and 0% of cases, respectively (P < 0.01). CONCLUSION: The meanings of the
      mnemonics for obstetric emergencies were frequently recalled incorrectly. This,
      together with the poor correlation between knowledge of maneuvers and their
      eponyms, limits their usefulness and indicates that teaching should focus on
      learning without relying on mnemonics and eponyms.

PMID- 24739478
TI  - Contribution of obstetrics and gynecology societies in South America to the
      prevention of unsafe abortion in the region.
AB  - Unsafe abortion is one of the most serious public health and human rights issues
      in South America. Rates are among the highest in the world and account for 13% of
      maternal deaths. Nine out of 10 South American countries have enrolled in the
      International Federation of Gynecology and Obstetrics (FIGO) Initiative for the
      Prevention of Unsafe Abortion and its Consequences. Each individual society of
      obstetrics and gynecology prepared a situational analysis, and an action plan was
      elaborated with the participation of their respective Ministries of Health,
      national and international agencies, and other collaborating institutions. Action
      plans were designed to respond to the problems identified in the situational
      analyses, with objectives corresponding with all or some of the 4 levels of
      prevention proposed in the FIGO initiative. This article reports the progress
      achieved in implementing the action proposed by each country, as well as some
      activities carried out in addition to those included in the formal plans. 

PMID- 24739480
TI  - Analysis of Swine Movement in Four Canadian Regions: Network Structure and
      Implications for Disease Spread.
AB  - Direct and indirect contacts among animal holdings are important in the spread of
      infectious diseases. The objectives of this study were to describe networks of
      pig movements and the sharing of trucks used for those movements between swine
      farms in four Canadian regions using network analysis tools and to obtain contact
      parameters for infectious disease spread simulation models. Four months of swine
      movement data from a pilot pig traceability programme were used. Two types of
      networks were created using three time scales (weekly, monthly and the full study
      period): one-mode networks of farm-to-farm direct contact representing animal
      shipments and two-mode networks representing the sharing of trucks between farms.
      Contact patterns among farms were described by estimating a range of relevant
      network measures. The overall network neglecting the four regions consisted of
      145 farms, which were connected by 261 distinct links. A total of 184 trucks were
      used to transport 2043 shipments of pigs during the study period. The median in-
      and out-degree for the overall one-mode network was 1 and ranged from 0 to 26 and
      0 to 10, respectively. The overall one-mode network had heterogeneous degree
      distribution, a high clustering coefficient and shorter average path length than
      would be expected for randomly generated networks of similar size. On average one
      truck was shared by four farms in the overall network, or by three farms when
      considered the monthly and weekly networks. Degree distribution of the two-mode
      overall network demonstrated characteristics of power-law distribution. For more
      than 50% of shipments on any given day, the same truck was used for at least one
      other shipment. Findings from this study are in agreement with previous work,
      which suggested that swine movement networks exhibit small-world and scale-free
      topologies. Furthermore, trucks used for the shipment of pigs can play an
      important role in connecting otherwise unconnected farms and may increase the
      spread of disease. 

PMID- 24739482
TI  - Immunohistochemical analysis of PDK1 expression in breast cancer.
AB  - BACKGROUND: 3-phosphoinositide-dependent protein kinase-1 (PDK1) functions
      downstream of phosphoinositide 3-kinase (PIK3) and activates members of the AGC
      family of protein kinases that are known to play crucial roles in physiological
      processes associated with cell metabolism, growth, proliferation and survival.
      Changes in the expression and activity of PDK1 and several AGC kinases have been
      linked to human disease, including cancer. METHODS: We used immunohistochemical
      analysis to determine PDK1 expression in 241 tumors from patients with breast
      cancer in which we had previously analyzed PIK3CA mutation status. RESULTS:
      Moderate or high expression of PDK1 was observed in 213 of the 241 cases (88%).
      There was no correlation between PIK3CA mutation status and PDK1 overexpression.
      CONCLUSION: Our findings indicate that PDK1 is independently activated in breast
      cancer and not only as part of the PIK3CA pathway, suggesting that PDK1 plays a
      specific and distinct role from the canonical PIK3/Akt pathway and promotes
      oncogenesis independently of AKT. Our data implicate PDK-1 and downstream
      components of the PDK-1 signaling pathway as promising therapeutic targets for
      the treatment of breast cancer.

PMID- 24739483
TI  - Dendritic cells in progressive renal disease: some answers, many questions.
AB  - Renal disease results from a variety of insults, but whatever its genesis,
      ongoing inflammation will drive progressive fibrotic disease. Dendritic cells
      link innate and adaptive immunity by presenting antigens, but they act also in an
      antigen-independent manner. While systemic dendritic cells (DCs) establish
      nephritogenic adaptive immunity, DCs are also present in the kidney. The
      tubulointerstitium is endowed with a network of mononuclear phagocytes, many
      having dendritic cell characteristics. While the roles of renal DCs are complex,
      recent evidence demonstrates that in adaptive immune responses affecting the
      kidney, DCs in the cortical interstitium express the chemokine receptor CX3CR1,
      are CX3CR1 dependent and are important in ongoing antigen recognition by effector
      CD4+ T cells, leading to progressive disease. Medullary DCs do not share this
      potent antigen-presenting function and CX3CR1 dependence. Though macrophages have
      a pathogenic role in antigen-independent renal fibrosis, whether interstitial DCs
      have any role is not clear. The participation of local and systemic DCs in
      progressive renal disease varies according to their involvement as antigen
      presenting or local innate cells, the nature of the pathogenic process, and the
      involvement of the glomerulus, the cortical tubulointerstitium and the medulla in
      disease. 

PMID- 24739484
TI  - Does increased water intake prevent disease progression in autosomal dominant
      polycystic kidney disease?
AB  - BACKGROUND: The clinical effects of increased water intake on autosomal dominant
      polycystic kidney disease (ADPKD) progression are unknown. METHODS: ADPKD
      patients with creatinine clearance ? 50 mL/min/1.73 m(2) were divided into high
      (H-, n = 18) and free (F-, n = 16) water-intake groups, mainly according to their
      preference. Prior to the study, 30 patients underwent annual evaluation of total
      kidney volume (TKV) and 24-h urine for an average of 33 months. During the 1-year
      study period, TKV and 24-h urine were analyzed at the beginning and end of the
      study and every 4 months, respectively. RESULTS: During the pre-study period,
      urine volume (UV) in the H-group was higher (P = 0.034), but TKV and kidney
      function and their slopes were not significantly different between the two
      groups. After the study commenced, UV further increased (P < 0.001) in the H
      group but not in the F-group. During the study period, TKV and kidney function
      slopes were not significantly different between the two groups (primary
      endpoint). Plasma copeptin was lower (P = 0.024) in the H-group than in the F
      group. TKV and kidney function slopes became worse (P = 0.047 and 0.011,
      respectively) after high water intake (H-group) but not in the F-group. High UV
      was associated with increased urine sodium, and urine sodium positively
      correlated with the % TKV slope (P = 0.014). CONCLUSIONS: Although the main
      endpoint was not significant, high water intake enhanced disease progression in
      the H-group when compared with the pre-study period. These findings necessitate a
      long-term randomized study before drawing a final conclusion.

PMID- 24739485
TI  - Cellular protection using Flt3 and PI3Kalpha inhibitors demonstrates multiple
      mechanisms of oxidative glutamate toxicity.
AB  - Glutamate-induced oxidative stress is a major contributor to neurodegenerative
      diseases. Here, we identify small-molecule inhibitors of this process. We screen
      a kinase inhibitor library on neuronal cells and identify Flt3 and PI3Kalpha
      inhibitors as potent protectors against glutamate toxicity. Both inhibitors
      prevented reactive oxygen species (ROS) generation, mitochondrial
      hyperpolarization and lipid peroxidation in neuronal cells, but they do so by
      distinct molecular mechanisms. The PI3Kalpha inhibitor protects cells by inducing
      partial restoration of depleted glutathione levels and accumulation of
      intracellular amino acids, whereas the Flt3 inhibitor prevents lipid
      peroxidation, a key mechanism of glutamate-mediated toxicity. We also demonstrate
      that glutamate toxicity involves a combination of ferroptosis, necrosis and AIF
      dependent apoptosis. We confirm the protective effect by using multiple
      inhibitors of these kinases and multiple cell types. Our results not only
      identify compounds that protect against glutamate-stimulated oxidative stress,
      but also provide new insights into the mechanisms of glutamate toxicity in
      neurons. 

PMID- 24739486
TI  - Five-year clinical performance of the dentine deproteinization technique in non
      carious cervical lesions.
AB  - OBJECTIVE: The aim of this study was to evaluate the 5-year clinical performance
      of composite restorations of non-carious cervical lesions (NCCL) using a total
      etch adhesive system with or without collagen removal with 10% sodium
      hypochlorite (NaOCl). METHODS: In this study randomized controlled split-mouth
      clinical trial, one-hundred and thirty-eight NCCL were restored into 30 patients.
      Each patient received at least one pair of composite restorations (Filtek A110/3M
      ESPE), bonded either with 2 techniques: Conventional Technique--acid etching with
      37% phosphoric acid+Prime & Bond NT (Denstply DeTrey); Deproteinization Technique
      -acid etching with 37% phosphoric acid+10% NaOCl for 1min+Prime & Bond NT. The
      two techniques were evaluated using the United States Public Health Service
      (USPHS) criteria at baseline, 18 months, 3 and 5 years. After five years, one
      hundred and six restorations were evaluated in 24 patients. Data were analyzed
      using the Chi-Square test (p<0.05). RESULTS: There were no statistically
      significant differences between the two techniques regarding the evaluated
      parameters (p>0.05). CONCLUSION: After 5 years, the application of 10% NaOCl
      deproteinization on etched dentine did not affect the clinical performance of
      composite restorations placed in NCCL when compared to the conventional total
      etch technique. CLINICAL SIGNIFICANCE: Clinical studies evaluating the
      performance of the Deproteinization Technique are scarce. In this study, this
      technique showed similar clinical performance at the end of 5 years when compared
      to a conventional total-etch technique.

PMID- 24739487
TI  - Intravenous pretreatment with emulsified isoflurane preconditioning protects
      kidneys against ischemia/reperfusion injury in rats.
AB  - BACKGROUND: Emulsified isoflurane (EIso) is a novel intravenous general
      anesthetic, which can provide rapid anesthetic induction and recovery. EIso
      preconditioning could attenuate heart, lung and liver ischemia/reperfusion (I/R)
      injury. We tested the hypothesis that intravenous pretreatment with EIso would
      protect kidneys against I/R injury by inhibiting systemic inflammatory responses
      and improving renal antioxidative ability. METHODS: RATS WERE RANDOMLY DIVIDED
      INTO THESE SIX GROUPS: sham, I/R, intralipid, 1, 2 or 4 ml/kg EIso. Rats were
      subjected to 45 min left renal pedicle occlusion followed by 3 h reperfusion
      after right nephrectomy. Rat were treated with intravenous 8% EIso with 1, 2 or 4
      ml/kg, or 30% intralipid with 2 ml/kg for 30 min before ischemia, respectively.
      After reperfusion, renal functional parameters, serum mediator concentrations and
      markers of oxidative stress in kidney tissues were determined, and renal
      histopathological analysis were performed. RESULTS: Serum creatinine, blood urea
      nitrogen, cystatin c, tumor necrosis factor-alpha, interleukin-6, and interleukin
      10 concentrations were significantly increased after renal I/R as compared to the
      sham group. So was renal tissue MDA content and histological scores, but renal
      tissue SOD activity was decreased. Additionally, severe morphological damages
      were observed in these study groups. In contrast, 2 or 4 ml/kg EIso reduced serum
      creatinine, blood urea nitrogen, cystatin c, tumor necrosis factor-alpha, and
      interleukin-6 levels, decreased renal tissue MDA content and histological scores,
      increased serum interleukin-10 level and tissue SOD activity as compared to the
      I/R, intralipid and 1 ml/kg EIso groups. Renal morphological damages were
      alleviated after pretreatment of 2 or 4 ml/kg EIso. CONCLUSIONS: Intravenous EIso
      produces preconditioning against renal I/R injury in rats, which might be
      mediated by attenuating inflammation and increasing antioxidation ability.

PMID- 24739488
TI  - PharmDock: a pharmacophore-based docking program.
AB  - BACKGROUND: Protein-based pharmacophore models are enriched with the information
      of potential interactions between ligands and the protein target. We have shown
      in a previous study that protein-based pharmacophore models can be applied for
      ligand pose prediction and pose ranking. In this publication, we present a new
      pharmacophore-based docking program PharmDock that combines pose sampling and
      ranking based on optimized protein-based pharmacophore models with local
      optimization using an empirical scoring function. RESULTS: Tests of PharmDock on
      ligand pose prediction, binding affinity estimation, compound ranking and virtual
      screening yielded comparable or better performance to existing and widely used
      docking programs. The docking program comes with an easy-to-use GUI within PyMOL.
      Two features have been incorporated in the program suite that allow for user
      defined guidance of the docking process based on previous experimental data.
      Docking with those features demonstrated superior performance compared to
      unbiased docking. CONCLUSION: A protein pharmacophore-based docking program,
      PharmDock, has been made available with a PyMOL plugin. PharmDock and the PyMOL
      plugin are freely available from
      http://people.pharmacy.purdue.edu/~mlill/software/pharmdock.

PMID- 24739489
TI  - Impact of fructose diet and renal failure on the function of pancreatic islets.
AB  - OBJECTIVES: This study was designed to evaluate the impact of fructose-rich diet
      and chronic kidney disease (CKD) on the in vitro function of pancreatic islets.
      METHODS: Fifty-four rats were divided into 3 equal groups as follows: control,
      rats with CKD 1/2 that underwent surgical uninephrectomy, and rats with CKD 5/6
      that underwent uninephrectomy and kidney cortex mass resection. Each group was
      further assigned to 3 diet protocols--regular diet, regular diet with 10%
      fructose (F10), and 60% fructose-rich diet (F60). After 8 weeks of insulin
      administration, C-peptide, glycated hemoglobin level, serum urea nitrogen,
      creatinine clearance, and homeostasis model assessment of insulin resistance were
      evaluated. Static glucose insulin stimulation test of isolated pancreatic islets
      and histologic analysis of pancreatic tissue were performed. RESULTS: The F10
      diet increased the levels of insulin and C-peptide in all groups. Homeostasis
      model assessment of insulin resistance was increased in all animals fed with
      fructose. The elevated levels of creatinine and diminished creatinine clearance
      were detected in CKD 5/6 rats fed with 60% fructose-rich diet. The F10 diet
      resulted in high levels of serum insulin and C-peptide and glucose-stimulated
      insulin secretion. Fructose-rich diet increased the islet size and number, with
      irregular morphology and exocrine tissue fibrosis. CONCLUSIONS: The fructose-rich
      diet accelerates the progression of CKD and affects the pancreatic islet
      function.

PMID- 24739490
TI  - Illness insight and neurophysiological error-processing deficits in
      schizophrenia.
AB  - Impaired illness insight in schizophrenia is associated with non-adherence and
      worse outcomes. Schizophrenia patients also exhibit error-monitoring deficits,
      which have been proposed to cause poor insight. To test this hypothesis, we
      examined whether schizophrenia patients' deficits in neurophysiological error
      monitoring indices, the error-related negativity (ERN) and error positivity (Pe)
      event-related potential (ERP) amplitudes, are associated with impaired insight.
      ERPs were recorded in 18 schizophrenia patients and 18 normal comparison
      participants during a Stroop task. Patients' subnormal ERN and Pe amplitudes did
      not correlate with insight, suggesting that impaired insight in schizophrenia
      stems from neurocognitive mechanisms other than deficient error monitoring. 

PMID- 24739491
TI  - Use of procalcitonin for the prediction and treatment of acute bacterial
      infection in children.
AB  - PURPOSE OF REVIEW: Procalcitonin (PCT) is increasingly utilized to determine the
      presence of infection or to guide antibiotic therapy. This review will highlight
      the diagnostic and prognostic utility of serum PCT in children. RECENT FINDINGS:
      Recent studies endorse the use of serum PCT to detect invasive infection, to
      differentiate sepsis from noninfectious systemic inflammatory response syndrome,
      and to guide antibiotic therapy. Typical values for maximal sensitivity and
      specificity are less than 0.5  ng/ml for noninfectious inflammation and greater
      than 2.0  ng/ml for bacterial sepsis. PCT appears to be a reliable indicator of
      infection. PCT has performed better than C-reactive protein in some settings,
      though pediatric comparative data are lacking. PCT may aid in diagnosing
      infection in challenging patient populations such as those with sickle cell
      disease, congenital heart defects, neutropenia, and indwelling central venous
      catheters. Antibiotic therapy tailored to serial PCT measurements may shorten the
      antibiotic exposure without increasing treatment failure. SUMMARY: PCT is a
      reliable serum marker for determining the presence or absence of invasive
      bacterial infection and response to antibiotic therapy. Tailoring antibiotics to
      PCT levels may reduce the duration of therapy without increasing treatment
      failure, but more research is needed in children.

PMID- 24739492
TI  - Prenatal imaging and postnatal presentation, diagnosis and management of
      congenital lung malformations.
AB  - PURPOSE OF REVIEW: Congenital lung malformations (CLMs) vary in their clinical
      presentation and severity. Increases in prenatal diagnosis, observed regression
      of certain lesions, and prognostic uncertainty are driving an evolution in
      management. RECENT FINDINGS: There has been an increase in the early diagnosis of
      these malformations, a change that is attributable to the routine use of prenatal
      ultrasound. Although prenatal diagnosis of CLMs using ultrasound and MRI has
      increased, chest radiography and computed tomography still play important roles
      in diagnosis. The management of these lesions depends on the type of malformation
      and symptoms. The treatment of asymptomatic patients with lung malformations is
      controversial, because the prognosis of these lesions is largely unknown.
      Proponents of early intervention argue that the complications of CLM, which may
      include infection, pneumothorax, bleeding and malignant transformation, justify
      surgery. Advocates of conservative management note that some CLMs disappear
      postnatally, and that the long-term complication rate following surgery is
      unknown. There is a need to obtain natural history data regardless of the
      therapeutic recommendations. SUMMARY: This article reviews the prenatal
      radiographic features and postnatal clinical findings of various CLMs and the
      dilemmas regarding treatment.

PMID- 24739493
TI  - Recent evidence on the management of bronchiolitis.
AB  - PURPOSE OF REVIEW: Bronchiolitis is a common condition in children less than 2 
      years of age and is a leading cause of infant hospitalization. Although there is
      significant variability in testing and treatment of children with bronchiolitis,
      diagnostic testing rarely improves care, and no currently available pharmacologic
      options have been proven to provide meaningful benefits or improve outcomes.
      RECENT FINDINGS: Beta-agonists continue to be used frequently despite evidence
      that they do not reduce hospital admissions or length of stay. In general,
      therapies initially considered promising were subsequently proven ineffective, a
      pattern seen in studies on corticosteroids, and more recently with nebulized
      racemic epinephrine and hypertonic saline. Recent research has improved our
      understanding of the viral epidemiology of bronchiolitis, with increasing
      recognition of viruses other than respiratory syncytial virus and better
      awareness of the role of viral coinfections. How these findings will translate
      into improved outcomes remains uncertain. SUMMARY: Much of the emphasis of the
      last few decades of bronchiolitis clinical care and research has centered on the
      identification and testing of novel therapies. Future quality improvement efforts
      should focus more on the limitation of unnecessary testing and treatments. Future
      research should include identification of subgroups of children with
      bronchiolitis that may benefit from focused clinical interventions.

PMID- 24739494
TI  - Disrupted lung development and bronchopulmonary dysplasia: opportunities for lung
      repair and regeneration.
AB  - PURPOSE OF REVIEW: Advances in medical therapy have increased survival of
      extremely premature infants and changed the pathology of bronchopulmonary
      dysplasia (BPD) from one of acute lung injury to a disease of disrupted lung
      development. With this evolution, new questions emerge regarding the molecular
      mechanisms that control postnatal lung development, the effect of early
      disruptions of postnatal lung development on long-term lung function, and the
      existence of endogenous mechanisms that permit lung regeneration after injury.
      RECENT FINDINGS: Recent data demonstrate that a significant component of
      alveolarization, the final stage of lung development, occurs postnatally.
      Further, clinical and experimental studies demonstrate that premature birth
      disrupts alveolarization, decreasing the gas exchange surface area of the lung
      and causing BPD. BPD is associated with significant short-term morbidity, and new
      longitudinal, clinical data demonstrate that survivors of BPD have long-standing
      deficits in lung function and may be at risk for the development of additional
      lung disease as adults. Unfortunately, current care is mainly supportive with few
      effective therapies that prevent or treat established BPD. These studies
      underscore the need to further elucidate the mechanisms that direct postnatal
      lung growth and develop innovative strategies to stimulate lung regeneration.
      SUMMARY: Despite significant improvements in the care and survival of extremely
      premature infants, BPD remains a major clinical problem. Although efforts should
      remain focused on the prevention of preterm labor and BPD, novel research aimed
      at promoting postnatal alveolarization offers a unique opportunity to develop
      effective strategies to treat established BPD.

PMID- 24739496
TI  - MAPs/bFGF-PLGA microsphere composite-coated titanium surfaces promote increased
      adhesion and proliferation of fibroblasts.
AB  - Infection and epithelial downgrowth are two major problems with maxillofacial
      transcutaneous implants, and both are mainly due to lack of stable closure of
      soft tissues at transcutaneous sites. Fibroblasts have been shown to play a key
      role in the formation of biological seals. In this work, titanium (Ti) model
      surfaces were coated with mussel adhesive proteins (MAPs) utilizing its unique
      adhesion ability on diverse inorganic and organic surfaces in wet environments.
      Prepared basic fibroblast growth factor (bFGF)-poly(lactic-co-glycolic acid)
      (PLGA) microspheres can be easily synthesized and combined onto MAPs-coated Ti
      surfaces, due to the negative surface charges of microspheres in aqueous
      solution, which is in contrast to the positive charges of MAPs. Titanium model
      surfaces were divided into three groups. Group A: MAPs/bFGF-PLGA microspheres
      composite-coated Ti surfaces. Group B: MAPs-coated Ti surfaces. Group C: uncoated
      Ti surfaces. The effects of coated Ti surfaces on adhesion of fibroblasts,
      cytoskeletal organization, proliferation, and extracellular matrix (ECM)-related
      gene expressions were examined. The results revealed increased adhesion (P <
      0.05), enhanced actin cytoskeletal organization, and up-regulated ECM-related
      gene expressions in groups A and B compared with group C. Increased proliferation
      of fibroblasts during five days of incubation was observed in group A compared
      with groups B and C (P < 0.05). Collectively, the results from this in vitro
      study demonstrated that MAPs/bFGF-PLGA microspheres composite-coated Ti surfaces
      had the ability to increase fibroblast functionality. In addition, MAPs/bFGF-PLGA
      microsphere composite-coated Ti surfaces should be studied further as a method of
      promoting formation of stable biological seals around transcutaneous sites. 

PMID- 24739495
TI  - Neuroimaging of mobility in aging: a targeted review.
AB  - BACKGROUND: The relationship between mobility and cognition in aging is well
      established, but the relationship between mobility and the structure and function
      of the aging brain is relatively unknown. This, in part, is attributed to the
      technological limitations of most neuroimaging procedures, which require the
      individual to be immobile or in a supine position. Herein, we provide a targeted
      review of neuroimaging studies of mobility in aging to promote (i) a better
      understanding of this relationship, (ii) future research in this area, and (iii)
      development of applications for improving mobility. METHODS: A systematic search
      of peer-reviewed studies was performed using PubMed. Search terms included (i)
      aging, older adults, or elderly; (ii) gait, walking, balance, or mobility; and
      (iii) magnetic resonance imaging, voxel-based morphometry, fluid-attenuated
      inversion recovery, diffusion tensor imaging, positron emission tomography,
      functional magnetic resonance imaging, electroencephalography, event-related
      potential, and functional near-infrared spectroscopy. RESULTS: Poor mobility
      outcomes were reliably associated with reduced gray and white matter volume.
      Fewer studies examined the relationship between changes in task-related brain
      activation and mobility performance. Extant findings, however, showed that
      activation patterns in the cerebellum, basal ganglia, parietal and frontal
      cortices were related to mobility. Increased involvement of the prefrontal cortex
      was evident in both imagined walking conditions and conditions where the
      cognitive demands of locomotion were increased. CONCLUSIONS: Cortical control of
      gait in aging is bilateral, widespread, and dependent on the integrity of both
      gray and white matter.

PMID- 24739498
TI  - Transgenerational transmission and child psychiatry.

PMID- 24739499
TI  - Prevalence of mental disorders in a Greek island.
AB  - In Greece, the need for epidemiological data became evident at the beginning of
      the mental health reform during 1983 with the emergence of the necessity to
      develop community-based mental health services. This survey was conducted in 2005
      by the Association for Regional Development and Mental Health (EPAPSY), supported
      by the local authorities. It followed the methodology of the survey "Mental
      Health in the General Population: Images and Realities" (MHGP), a large scale
      multisite epidemiological research conducted by the World Health Organization
      Collaborative Centre of Lille in France and other countries. The aim of this
      study was to assess prevalence, sociodemographic and comorbidity patterns of
      mental disorders in the general adult population of Evia Island, Greece. This was
      a cross-sectional survey investigating point, period and lifetime prevalence of
      mental disorders. The target population was the non-institutionalized adult
      population of island of Evia (population 230,000 people). The Mini International
      Neuropsychiatric Interview and a sociodemographic data questionnaire were
      administered by trained interviewers to 900 residents of Evia. The quota sampling
      method was used to obtain a sample representative of the target population.
      Lifetime prevalence of any disorder, as identified by the MINI, was 29%. The
      prevalence of depression was high, with 17.5% of women and 14.6% of men currently
      meeting the criteria for diagnosis. Affective and anxiety disorders were found to
      be more frequent in women than men, except for dysthymia, social phobia and post
      traumatic stress disorder which were slightly more frequent in men. The
      prevalence of psychiatric disorders in Evia was much higher than the prevalence
      found by other epidemiological studies in Greece and among the highest in
      Southern Europe. The high prevalence of mental disorders found in Evia means that
      almost one third of the population will suffer from a clinically significant
      disorder in their lifetime. Therefore, the resulting social burden is very
      relevant and requires the inclusion of mental health care among the main goals of
      a public health strategy. Methodological issues concerning the comparison of
      results between different countries, the limitations of the study and the rates
      of alcohol use disorders discussed. High rates of mental disorders are related to
      demographic changes, such as the increasing are size of elderly population, and
      probably to economic hardship and rise in unemployment. Results should be taken
      into consideration for the planning and development of interventions for
      vulnerable groups. 

PMID- 24739497
TI  - Concordant or discordant results by the tuberculin skin test and the quantiFERON
      TB test in children reflect immune biomarker profiles.
AB  - The tuberculin skin test (TST) and QuantiFERON-TB-Gold-In-tube (QFTGIT) are
      adjunctive tests used in the diagnosis of pediatric tuberculosis (TB). Neither
      test can rule out TB; however, a positive test usually triggers preventive
      treatment in TB contacts aged <5 years. TST and QFTGIT can give divergent results
      and it is unclear how discordant results should be interpreted in terms of TB
      risk and preventive treatment. To understand the immune processes underlying
      concordant or discordant TST and QFTGIT results, we analyzed immune responses in
      children from Palamaner Taluk in India (a TB-endemic region with routine neonatal
      BCG vaccination) who were referred to a TB case verification ward on suspicion of
      TB. Two hundred and ten children aged <3 years were classified according to their
      TST and QFTGIT results, and their immune responses analyzed by dual-colour
      Reverse-Transcriptase-Multiple-Ligation-dependent-Probe-Amplification, using a
      panel of 45 genes and a 10-plex antigen-specific enzyme-linked immunosorbent
      assay. We show that immune biomarkers FPR1, TNFRSF1A and interferon (IFN)-gamma
      are upregulated (all P<0.05) in concordant test-positive children, whereas BPI is
      downregulated (P<0.05). In contrast, SEC14L1 (P=0.034) and Interferon gamma
      induced protein 10 (IP-10) (P=0.001) are differentially expressed between the
      TST+QFTGIT- /TST-QFTGIT+ groups. Known TB exposure was more frequent in
      concordant positive children and results were consistent with elevated expression
      of genes associated with inflammatory responses. Children with discordant test
      results displayed a mixed profile with activation of both pro- and anti
      inflammatory markers. TST and/or QFTGIT positivity appears to reflect distinct
      but overlapping aspects of host immunity.

PMID- 24739500
TI  - Cognitive impairments and psychopathological parameters in patients of the
      schizophrenic spectrum.
AB  - Cognitive impairment is a core feature of schizophrenia and it is considered by
      many researchers as one of the dimensional components of the disorder. Cognitive
      dysfunction occurs in 85% of schizophrenic patients and it is negatively
      associated with the outcome of the disorder, the psychosocial functioning of the
      patients, and non-compliance with treatment. Many different cognitive domains are
      impaired in schizophrenia, such as attention, memory, executive functions and
      speech. Nowadays, it is argued that apart from clinical heterogeneity of
      schizophrenia, there is probable heterogeneity in the accompanying neurocognitive
      dysfunction. Recent studies for cognitive dysfunction in schizophrenia employ
      computerized assessment batteries of cognitive tests, designed to assess specific
      cognitive impairments. Computerized cognitive testing permits for more detailed
      data collection (e.g. precise timing scores of responses), eliminates
      researcher's measurement errors and bias, assists the manipulation of data
      collected, and improves reliability of measurements through standardized data
      collection methods. The aims of the present study are: the comparison of
      cognitive performance of our sample of patients and that of healthy controls, on
      different specific cognitive tests, and the testing for possible association
      between patients' psychopathological symptoms and specific cognitive impairments,
      using the Cogtest computerized cognitive assessment battery. 71 male inpatients
      diagnosed with schizophrenia or other psychotic spectrum disorders (mean = 30.23
      +/- 7.71 years of age), admitted in a psychiatric unit of the First Department of
      Psychiatry, Athens University Medical School, Eginition Hospital (continuous
      admissions) were studied. Patients were excluded from the study if they suffered
      from severe neurological conditions, severe visual or hearing impairment, mental
      retardation, or if they abused alcohol or drugs. The patients' diagnoses were
      based on the semi-structured diagnostic interview "Diagnostic Interview for
      Psychosis" (DIP) and were clinically confirmed by two independent expert
      psychiatrists, according to the criteria of DSM-IVTM. Our healthy control group
      consisted of 20 healthy male participants (mean = 31.65 +/- 5.90 years of age),
      who met the same inclusion criteria for the study as the patient group, as well
      as the same exclusion criteria from the study, having no history of psychiatric
      disorders. All statistical analyses were conducted using the statistical package
      SPSS.17. According to our results, healthy controls cognitively outperform our
      patient sample in all cognitive tests, with the differences between performances
      being statistically significant. Results concerning the association between
      psychotic symptoms and cognitive deficits of our patients indicated that
      hallucinations, highly organized delusions, persecutory delusions, agitation,
      catatonia and inappropriate affect did not associate with any subtype of
      cognitive deficit. Blunted affect associated significantly with response
      inhibition ("GoNoGo test", p = 0.007), and poor speech associated significantly
      with declarative memory of faces ("FMT test", p = 0.002). Moreover, psychomotor
      ability (non-dominant hand) associated significantly with generalized delusions
      ("TST test", p = 0.033), and with constricted affect ("TST test", p = 0.026).
      Furthermore, there was a tendency towards significance association between
      persecutory delusions and executive function ("CPT test", p = 0.053),
      inappropriate affect and declarative face memory ("FMT test", p = 0.056), and
      psychomotor ability and poor speech (p = 0.086).

PMID- 24739501
TI  - Assessment of the Greek worry-related metacognitions: the Greek version of the
      Metacognitions Questionnaire (MCQ-30).
AB  - The Metacognitions Questionnaire-30 (MCQ-30), developed by Wells and Cartwright
      Hatton (2004), represents a multidimensional measure of metacognitive factors
      considered to be important in the metacognitive model of psychological disorders.
      The primary aim of the present study was to examine internal consistency, test
      retest reliability, convergent validity and the factor structure of the Greek
      version of the MCQ-30. Moreover, we investigated the associations of the
      extracted factors with trait anxiety in a Greek sample. The study sample
      consisted of 547 non-clinical participants (213 males and 334 females). All
      participants completed the Greek version of the MCQ-30. A subsample of 157
      participants also completed the Trait Anxiety subscale of the State -Trait
      Anxiety Inventory and the Meta-worry subscale of the Anxious Thought Inventory.
      Thirty participants were retested with the MCQ-30 over a retest interval ranging
      from three to five weeks. The results confirmed the dimensionality of the MCQ-30
      and five factors were extracted consistent with the original English version: (1)
      positive beliefs about worry, (2) negative beliefs about worry concerning
      uncontrollability and danger, (3) cognitive confidence, (4) beliefs about the
      need to control thoughts and the negative consequences of not controlling them,
      and (5) cognitive selfconsciousness. The MCQ-30 showed high levels of internal
      consistency and test-retest reliability. The correlation between MCQ-30 total
      score and AnTI-MW was strong, indicating high level of convergent validity.
      Moreover, all correlations between MCQ-30 total and subscale scores and STAI-T
      were significant apart from the correlation between 'cognitive confidence' and
      trait anxiety. The Greek sample scored higher in the MCQ-30 and its subscales
      than the English sample in the original study. Women scored significantly higher
      than men in the overall MCQ-30 and the "uncontrollability and danger" and "need
      to control thoughts" subscales, whereas no significant differences between
      genders had been found in the original study. The assumption that the differences
      in score levels and the gender effect might reflect cultural differences warrants
      further investigation. The findings of the present study indicate that the Greek
      version of the MCQ-30 is a comprehensible and psychometrically adequate
      instrument, as well as a reliable tool in assessing a range of dimensions of
      worry-related metacognitions in the Greek population. The Greek version of this
      scale facilitates crosscultural research in metacognition and wider testing of
      the metacognitive approach to emotional vulnerability, psychological disturbances
      and mental disorders. 

PMID- 24739502
TI  - Management in child and adolescent psychiatry: how does it look in the Balkans?
AB  - This paper examines the situation of child and adolescent psychiatry in the
      following Balkan countries: Greece, Serbia, Bulgaria, Romania, Bosnia and
      Herzegovina, FYROM, and Montenegro. With the exception of Greece, these countries
      are new democracies, with their mental health services in a transitional stage of
      organization. Overall, they have initiated programmes to move psychiatric care
      towards deinstitutionalization, developing outpatient infrastructures to handle
      psychiatric disorders. Child psychiatry as a specialization is still less
      developed than adult psychiatry at a significant, albeit different degree among
      these countries. The number of mental health services offered to children and
      adolescents is deemed insufficient, and the type of services limited and lacking.
      This situation is also reflected in the small number of child psychiatrists and
      other mental health specialists for children and adolescents, as well as in the
      complete lack (Montenegro) or deficiency of special programmes and actions for
      children and adolescents. The same also applies to mental health legislation.
      Greece is the exception in the development of the entire spectrum of services,
      the number of specialists, and the establishment of an adequate legislation
      framework reinforced by the incorporation of all international treaties on
      children's rights; although the recent economic crisis has affected the country
      negatively, threatening with regression to pre-reformational practices. Children
      and adolescents in need of mental health care have been increasing in all
      countries. The effect of violent and sudden changes taking place in most
      countries is a major factor for the emergence of increased and stress-related
      psychopathology and psychosocial problems in children and families. In all
      countries, there is a significant development of nongovernmental organizations
      undertaking a large part of reformation work. There is also the disconcerting
      phenomenon of professional exhaustion and the migration of experts from their
      countries. Finally, there is the common need to develop educational programmes
      and related clinical practices in all degrees of prevention, promoting
      interdisciplinary cooperation, the biopsychosocial approach to understanding and
      dealing with mental health issues, as well as the development of cooperation
      among all institutions concerning children (education, health, etc.). All this
      should be reflected in a national plan to promote child mental health as the
      foundation upon which the necessary cooperation among Balkan countries would be
      established in order to promote research, the exchange of experiences, common
      practices, mutual understanding, and common interests. 

PMID- 24739503
TI  - Psychiatry training in the United Kingdom--Part 1: a general overview.
AB  - In recent years there has been a strong trend of emigration of Greek medical
      doctors. The reason for this phenomenon is certainly multifactorial, but it has
      been greatly exacerbated due to the latest financial crisis. The United Kingdom
      is one of the most popular destinations amongst emigrating Greek psychiatric
      doctors, as reflected by official data and by the sheer volume of requests for
      information received by the United Kingdom Division of the Hellenic Psychiatric
      Association. There are many systemic and practical differences between the Greek
      and the United Kingdom health systems, which complicate training and further
      career decisions. These complex differences make it hard for psychiatric doctors
      to decide which steps to take, and often result in them making the "wrong"
      decision. These "wrong" decisions are very often the result of poor information
      or misinformation. For instance many doctors are confused about the equivalence
      of training and service grades between Greece and the United Kingdom, what a good
      portfolio means, or the significance of the MRCPsych exam. This information
      exists, sometimes in comprehensive ways on the internet, but for doctors who are
      not familiar with the system, finding this information can be a time-consuming
      and laborious task. Therefore, providing a starting point with realistic and
      useful information about psychiatric training and generally career progression in
      the United Kingdom to Greek psychiatric doctors has become very important. The
      United Kingdom Division of the Hellenic Psychiatric Association has decided to
      pick up the role of providing exactly that information. The first part of this
      two-piece paper provides a starting point for Greek doctors considering the move
      to the United Kingdom for training and/or work in psychiatry. Firstly, it gives a
      general overview of psychiatric training in the United Kingdom, and explains that
      the pragmatic equivalence between training stages between Greece and the United
      Kingdom often differs from the formal equivalence. It also explains the salient
      differences between the Greek and the United Kingdom's health systems and
      highlights some common pitfalls. Furthermore, it explains some career options
      psychiatric trainees and specialists can follow in the UK, including clinical and
      academic training and service posts. The second part of this paper explores in
      more detail the structure and inner workings of psychiatric training, again
      emphasising the important differences between the Greek and the United Kingdom's
      training systems, and highlighting those differences that may be useful to a
      transitioning doctor. This diptych is meant to be informative, not advisory, and
      thus is not meant to either encourage or discourage the migration of interested
      parties. 

PMID- 24739504
TI  - Adenovirus36 infection expresses cellular APMI and Visfatin genes in overweight
      Uygur individuals.
AB  - OBJECTIVE: This study is to determine if Adenovirus type 36 (Ad36) infection is
      related to macrophage infiltration in the obese group and non-obese group and the
      related molecular mechanisms. METHODS: Ninety obesity patients and 95 non-obesity
      Uygur individuals were enrolled in this study. CD68 levels in abdominal
      subcutaneous and omental adipose tissues were detected by immunohistochemistry.
      The cytokine expression levels of adiponectin (APMI) and visfatin in serum were
      measured by enzyme-linked immunosorbent assay. Infection of 3T3-L1 cells with
      Ad36 was performed. Real-time PCR was performed to determine expression levels of
      APMI and Visfatin genes in the 3T3-L1 preadipocytes infected with Ad36. RESULTS:
      In the obese individuals infected with Ad36, the expression levels of adiponectin
      and visfatin in serum was elevated. For the individuals infected with Ad36, the
      macrophage infiltration (as indicated by CD68 level) in the obese group was also
      significantly higher than that in the non-obese group (P < 0.05) in both
      abdominal subcutaneous and omental adipose tissues. The real-time PCR results
      indicated that APMI mRNA levels and Visfatin mRNA levels in Ad36 infected cells
      were significantly increased. CONCLUSIONS: Ad36 infection may be a factor related
      with macrophage infiltration in adipose tissues of the obese patients. The APMI
      and Visfatin genes may be involved in the mechanism underlying the effect of Ad36
      infection on the obese patients. VIRTUAL SLIDES: The virtual slide(s) for this
      article can be found here:
      http://www.diagnosticpathology.diagnomx.eu/vs/1849614638119816.

PMID- 24739505
TI  - Age-related differences in outcomes and etiologies of acute abdominal pain based
      on a national administrative database.
AB  - Acute abdominal pain is one of the most frequent causes of admission to emergency
      departments. However, there is a shortage of detail information showing the
      difference of outcomes or etiology of acute abdominal pain according to age. We
      therefore conducted an epidemiological analysis to reveal the difference between
      age on outcomes and etiology of acute abdominal pain using an administrative
      database associated with the Diagnosis Procedure Combination (DPC) system. We
      obtained discharge data relating to 12,209 patients with acute abdominal pain
      from 931 DPC participation hospitals between 2009 and 2011 in Japan. We compared
      length of hospital stay (LOS), in-hospital mortality, and etiology of acute
      abdominal pain between age categories. Patients were divided into five age groups
      as follows: < 20 (n = 1,106), 20-39 (n = 3,353), 40-59 (n = 2,925), 60-79 (n =
      3,144), and >= 80 years (n = 1,681). Longer LOS and higher in-hospital mortality
      were observed in patients aged >= 80 years (p < 0.001). Regarding etiologies of
      acute abdominal pain, intestinal infection or acute appendicitis were more
      frequent in patients aged < 20 or 20-39 years, while ileus or cholelithiasis were
      more frequent in patients aged 60-79 or >= 80 years in both male and female
      patients (p < 0.001). This study demonstrated the significant differences between
      age with regard to the patient outcomes and etiology of acute abdominal pain. The
      current findings highlight the importance of improving the quality of medical
      care for patients with acute abdominal pain. 

PMID- 24739506
TI  - Swallowing transit times and valleculae residue in stable chronic obstructive
      pulmonary disease.
AB  - BACKGROUND: Breathing and swallowing are physiologically linked to ensure
      effortless gas exchange during oronasal breathing and to prevent aspiration
      during swallowing. Studies have indicated consistent aspiration in chronic
      obstructive pulmonary disease, mainly related to delayed swallowing reflex and
      problems with lingual propulsion and pharyngeal peristalsis as a result of
      bilateral weakness and incoordination of the related muscles. The purpose of the
      present study was to evaluate swallowing transit times and valleculae residue
      characteristics of stable COPD patients who have no swallowing complaints.
      METHODS: Our study population included 20 stable patients with COPD and no
      swallowing complaints and 20 healthy controls. Swallowing was assessed through
      videofluoroscopic examination and involved the analysis of the following
      parameters: (1) pharyngeal stages of deglutition; (2) the duration of bolus
      movement through the oral cavity and pharynx (i.e. transit times); (3) valleculae
      residue ratio; (4) penetration/aspiration. RESULTS: Participants of the study did
      not present any signs of penetration-aspiration for any of the tested
      consistencies. Patients with COPD presented longer pharyngeal transit times
      during the ingestion of the liquid consistency and during the ingestion of the
      paste consistency. Regarding the duration of tongue base contact with the
      posterior pharyngeal wall, COPD patients also presented longer durations for the
      liquid and paste consistencies. No significant difference was observed for the
      distribution of individuals among the different valleculae residue severity
      levels. CONCLUSIONS: Our study suggests that stable COPD patients may present
      physiological adaptations as a protective swallowing maneuver to avoid
      aspiration/penetration of pharyngeal contents. Moreover, valleculae residue
      cannot be seen as an isolated factor when trying to explain swallowing
      alterations in this population.

PMID- 24739507
TI  - Role of cervical ultrasound in detecting thyroid pathology in primary
      hyperparathyroidism.
AB  - BACKGROUND: Minimally invasive parathyroidectomy for primary hyperparathyroidism
      is made possible with accurate preoperative imaging. In addition to the detection
      of parathyroid adenomas, cervical ultrasound also provides concomitant assessment
      of the thyroid gland, and many surgeons believe that it is essential. However,
      the incidental identification of thyroid nodules may then subject patients to
      further workup and potentially invasive thyroid procedures. We sought to
      determine the long-term consequence of omitting preoperative ultrasound on the
      development of thyroid pathology and cancer. METHODS: At our institution, 222
      patients with primary hyperparathyroidism underwent parathyroidectomy without
      preoperative cervical ultrasound from 1990-2001. Thyroid pathology discovered by
      follow-up after parathyroidectomy, subsequent biopsy, and surgical interventions
      were analyzed. RESULTS: Of the 222 patients who underwent parathyroidectomy, the
      mean age was 55 +/- 1 y and 149 were female (67%). In the course of their follow
      up after parathyroidectomy, 13 patients (6%) received a cervical ultrasound, and
      seven of 13 (3%) underwent fine needle aspiration of a thyroid nodule. Only one
      of seven (0.4% of all patients) was ultimately diagnosed with thyroid cancer.
      Four additional patients were discovered to have thyroid malignancies as a result
      of intraoperative decision making. All five patients are currently alive with an
      average follow-up time of 14.9 +/- 1.6 y. No patients in this series had an
      unnecessary thyroid intervention. CONCLUSIONS: In patients who underwent
      parathyroidectomy without a preoperative ultrasound, only a small number (0.4%)
      were subsequently diagnosed with thyroid cancer. Furthermore, omission of
      ultrasound during the localization of parathyroid glands does not have a negative
      impact on the diagnosis of thyroid pathology as all patients who had thyroid
      cancer had good outcomes, and in fact, may prevent unnecessary thyroid
      interventions. Therefore, the use of cervical ultrasound for parathyroid
      localization should be considered optional rather than essential.

PMID- 24739508
TI  - Surgical site infection after thyroidectomy: a rare but significant complication.
AB  - BACKGROUND: Surgical site infections (SSIs) after thyroidectomy are rare but can
      have significant consequences. Thyroidectomy is a clean case, and the patterns
      for use of prophylactic antibiotics vary. We hypothesized that patient and
      operative characteristics may predict a higher risk of SSI, and that SSI are
      associated with other complications leading to increased resource utilization.
      METHODS: Data from the American College of Surgeons National Surgical Quality
      Improvement Program dataset for patients who underwent thyroidectomy through
      cervical incisions from 2005-2011 were included. Bivariate analysis using t-tests
      and chi-square tests were performed, and variables with P<0.2 were considered for
      inclusion in a multivariate logistic regression model. RESULTS: A total of 49,326
      patients underwent thyroidectomy from 2005-2011 and 179 (0.36%) had an SSI. On
      multivariate analysis, the strongest predictors of SSI were operative time
      (P<0.001) and wound classification clean-contaminated (odds ratio 6.1; 95%
      confidence interval, 3.6, 10.3). Preoperative factors associated with SSI on
      multivariate analysis had lower magnitudes of influence on SSI risk but included
      obesity, alcohol use, and nonindependent functional status. Patients with SSI
      were more likely to have a wound dehiscence, renal insufficiency, bleeding
      requiring transfusion, and return to the operating room on a multivariate model
      of outcomes. CONCLUSIONS: Although rare, SSI after thyroidectomy are associated
      with other postoperative complications. We have identified preoperative and
      intraoperative factors that are associated with SSI, and this may help identify
      high-risk patients who may benefit from selective use of antibiotics.

PMID- 24739509
TI  - Laparoscopic pyloromyotomy: comparing the arthrotomy knife to the Bovie blade.
AB  - BACKGROUND: Laparoscopic pyloromyotomy was performed at our institution using an
      arthrotomy knife until it became unavailable in 2010. Thus, we adapted the use of
      the blunt Bovie tip, which can be used with or without electrocautery to perform
      the myotomy. This study compared the outcomes between using the arthrotomy knife
      versus the Bovie blade in laparoscopic pyloromyotomies. MATERIALS AND METHODS:
      Retrospective review was performed on all laparoscopic pyloromyotomy patients
      from October 2007 to September 2012. Arthrotomy knife pyloromyotomy patients were
      compared with those performed with the Bovie blade. Patient demographics,
      diagnostic measurements, electrolyte levels, length of stay, operative time, and
      complications were compared. RESULTS: A total of 381 patients were included, with
      191 in the arthrotomy group and 190 in the Bovie blade group. No significant
      differences existed between groups in age, weight, gender, pyloric dimensions,
      electrolyte levels, or length of stay. Mean operative times were 15.8+/-5.6 min
      with knife and 16.4+/-5.3 min for Bovie blade (P=0.24). In the arthrotomy knife
      group, there was one incomplete pyloromyotomy and one omental herniation. There
      was one wound infection in each group. Readmission rate was greater in the
      arthrotomy knife group (5.7%) versus the Bovie blade group (3.1%). CONCLUSIONS:
      The Bovie blade appears to offer no objective disadvantages compared with the
      arthrotomy knife when performing laparoscopic pyloromyotomy.

PMID- 24739510
TI  - The effect of topically applied tissue expanders on radial forearm skin
      pliability: a prospective self-controlled study.
AB  - BACKGROUND: The use of pre-operatively applied topical tissue expansion tapes
      have previously demonstrated increased rates of primary closure of radial forearm
      free flap donor sites. This is associated with a reduced cost of care as well as
      improved cosmetic appearance of the donor site. Unfortunately, little is known
      about the biomechanical changes these tapes cause in the forearm skin. This study
      tested the hypothesis that the use of topically applied tissue expansion tapes
      will result in an increase in forearm skin pliability in patients undergoing
      radial forearm free flap surgery. METHODS: Twenty-four patients scheduled for
      head and neck surgery requiring a radial forearm free flap were enrolled in this
      prospective self-controlled observational study. DynaClose tissue expansion tapes
      (registered Canica Design Inc, Almonte, Canada) were applied across the forearm
      one week pre-operatively. Immediately prior to surgery, the skin pliability of
      the dorsal and volar forearm sites were measured with the Cutometer MPA 580
      (registered Courage-Khazaka Electronic GmbH, Cologne, Germany) on both the
      treatment and contralateral (control) arms. Paired t-tests were used to compare
      treatment to control at both sites, with p < 0.025 defined as statistically
      significant. RESULTS: There was a statistically significant increase in
      pliability by a mean of 0.05 mm (SD = 0.09 mm) between treatment and control arms
      on the dorsal site (95% CI [0.01, 0.08], p = 0.018). This corresponded to an 8%
      increase in pliability. In contrast, the volar site did not show a statistically
      significant difference between treatment and control (mean difference = 0.04 mm,
      SD = 0.20 mm, 95% CI [-0.04, 0.12], p = 0.30). CONCLUSIONS: This result provides
      evidence that the pre-operative application of topical tissue expansion tapes
      produces measurable changes in skin biomechanical properties. The location of
      this change on the dorsal forearm is consistent with the method of tape
      application. While this increase in skin pliability may account for the improved
      rate of primary donor site closure reported using this technique, the results did
      not reach our definition of clinical significance.

PMID- 24739511
TI  - Assessing the relevance, efficiency, and sustainability of HIV/AIDS in-service
      training in Nigeria.
AB  - More than three million people in Nigeria are living with HIV/AIDS. In order to
      reduce the HIV/AIDS burden in Nigeria, the US Government (USG) has dedicated
      significant resources to combating the epidemic through the President's Emergency
      Plan for AIDS Relief (PEPFAR). In-service training (IST) of health workers is one
      of the most commonly used strategies to improve the quality and coverage of
      HIV/AIDS services. At USAID/Nigeria's request, the USAID-funded CapacityPlus
      project conducted an assessment of PEPFAR-funded IST for all cadres of health
      workers in Nigeria. Using the IST Improvement Framework, developed by the USAID
      Applying Sciences to Strengthen and Improve Systems Project (ASSIST), as a guide,
      the authors developed a survey tool to assess the efficiency, effectiveness and
      sustainability of IST provided between January 2007 and July 2012 by PEPFAR
      funded implementing partners in Nigeria. The instrument was adapted to the
      Nigerian context and refined through a stakeholder engagement process. It was
      then distributed via an online platform to more than 50 PEPFAR-funded
      implementing partners who provided IST in Nigeria. A total of 39 implementing
      partners completed the survey. Our survey found that PEPFAR implementing partners
      have been providing a wide range of IST to a diverse group of health workers in
      Nigeria since 2007. Most trainings are developed using national curricula,
      manuals and/or other standard operating procedures. Many of the partners are
      conducting Training Needs Assessments to inform the planning, design and
      development of their training programs. However, the assessment also pointed to a
      number of recommendations to increase the efficiency, effectiveness and
      sustainability of PEPFAR-funded IST. These actions are as follows: improve
      collaboration and coordination among implementing partners; apply a more diverse
      and cost-effective set of training modalities; allocate funding specifically for
      the evaluation of the effectiveness of training; improve links between IST and
      both continuing professional development and pre-service education; require
      implementing partners to create sustainability plans to transition training from
      PEPFAR funding to other funding sources; and develop a training information
      management system to track key aspects of IST, such as the number and types of
      providers, courses, and participants of PEPFAR-funded IST. 

PMID- 24739513
TI  - Control of Bovine Brucellosis from Persistently Infected Holdings Using RB51
      Vaccination with Test-and-Slaughter: A Comparative Case Report from a High
      Incidence Area in Portugal.
AB  - Bovine brucellosis due to Brucella abortus infection causes significant
      reproductive and production losses in cattle and is a major zoonosis. Eradication
      of this disease has proved difficult to achieve in Portugal where it still occurs
      in some regions despite an ongoing national eradication programme. In 2004, the
      Alentejo region, a major cattle producing area, reported one of the highest
      levels of bovine brucellosis in the country, especially in one divisional area.
      In that area, bovine brucellosis was particularly problematic in a holding of ten
      herds, the largest extensive cattle unit in the country, which remained infected
      despite an extensive test-and-slaughter programme and depopulation of five herds.
      A 5-year programme of RB51 vaccination with biannual test-and-slaughter was thus
      implemented in 2004. The apparent animal seroprevalence decreased from 19%
      (646/3,400) to 3% (88/2930) on the third herd-level test and remained below 0.8%
      (27/3324) after the fourth test. After the tenth test, the holding had a
      prevalence of 0.1% (2/2332) and only one herd remained positive with a within
      herd prevalence of 1.1% (2/177). The results were compared to all other herds (n
      = 10) in the divisional area that were also persistently infected but were
      subject only to test-and-slaughter before being depopulated. In these herds, the
      strategy of test-and-slaughter did not reduce the prevalence, which remained
      significantly higher than the vaccinated group (median = 0.48% and 8.5% in
      vaccinated versus non-vaccinated herds; Wilcoxon rank sum test; P < 0.01). The
      success of this pilot programme in continental Portugal provided a valuable case
      study to the official veterinary services by illustrating the value of RB51
      vaccination with parallel testing and improved biosecurity as a comprehensive and
      sustainable strategy for bovine brucellosis control in persistently infected
      herds.

PMID- 24739512
TI  - Cell cycle-dependent chromatin shuttling of HBO1-JADE1 histone acetyl transferase
      (HAT) complex.
AB  - HAT HBO1 interacts with 2 isoforms of JADE1: JADE1S and JADE1L. JADE1 promotes
      acetylation of nucleosomal histones by HBO1. HBO1-JADE1 complex facilitates cell
      proliferation by unclear mechanisms. Here we report intracellular chromatin
      shuttling of HBO1-JADE1 complex during mitosis coupled to phosphorylation of
      JADE1. In interphase of dividing cells JADE1S was localized to the nucleus and
      associated with chromatin. As cells approached mitosis, specifically prophase,
      JADE1S dissociated from chromatin and associated with cytoplasm. JADE1S chromatin
      re-association began in telophase and paralleled nuclear envelope membrane
      reassembly. By early G1, JADE1S was re-associated with chromatin and localized to
      the nucleus. Importantly, cytoplasmic but not chromatin-associated JADE1 protein
      was phosphorylated. Mass-Spectrometric analysis of JADE1S protein isolated from
      G2/M-arrested cells identified 6 phosphorylated amino acid residues: S89, T92,
      S102, S121, S392, and T468, including 3 novel sites. Temporally, JADE1S
      phosphorylation and dephosphorylation during mitosis correlated with JADE1S
      chromatin dissociation and recruitment. JADE1S chromatin recruitment was
      accompanied by the global histone H4 acetylation. Pharmacological inhibitor of
      Aurora A kinase prevented JADE1S protein band shift and chromatin dissociation,
      suggesting regulatory function for phosphorylation. In vivo experiments supported
      our in vitro results. In mouse kidneys, JADE1S transiently accumulated in the
      cytoplasm of tubular epithelial cells during kidney regeneration. The transient
      increase in the number of cells with cytoplasmic JADE1S directly correlated with
      activation of tubular cell proliferation and inversely correlated with the number
      of cells with nuclear JADE1S staining, supporting biological role of HBO1-JADE1
      shuttling during organ regeneration.

PMID- 24739514
TI  - Local adaptation limits lifetime reproductive success of dispersers in a wild
      salmon metapopulation.
AB  - Demographic and evolutionary dynamics in wild metapopulations are critically
      affected by the balance between dispersal and local adaptation. Where populations
      are demographically interconnected by migration, gene flow is often assumed to
      prevent local adaptation. However, reduced fitness of immigrants may limit gene
      flow between populations adapted to distinct habitat types, although direct
      quantification of the lifetime reproductive success of immigrants in the wild is
      lacking. Here, we show that dispersers between stream-spawning populations of
      sockeye salmon (Oncorhynchus nerka) had similar reproductive success to those
      that spawned in their natal stream, whereas dispersers from a different habitat
      (nearby lake beaches) produced half as many offspring. The stream- and beach
      spawning ecotypes exhibited striking morphological differences despite their
      close spatial proximity, yet dispersal from the beach to the streams was more
      common than dispersal between streams, presenting empirical evidence that
      variation in immigrant reproductive success is important for the maintenance of
      intraspecific biodiversity. 

PMID- 24739515
TI  - Efficacy of N-acetylcysteine in preventing atrial fibrillation after cardiac
      surgery: a meta-analysis of published randomized controlled trials.
AB  - BACKGROUND: Atrial fibrillation is a common complication after cardiac surgery.
      The aim of this study is to evaluate whether N-acetylcysteine (NAC) could prevent
      postoperative atrial fibrillation (POAF). METHODS: PubMed, Embase and Cochrane
      Center Register of Controlled Trials were searched from the date of their
      inception to 1 July 2013 for relevant randomized controlled trials (RCTs), in
      which NAC was compared with controls for adult patients undergoing cardiac
      surgery. Outcome measures comprised the incidence of POAF, all-cause mortality,
      length of intensive care unit (ICU) stay, hospital length of stay, and the
      incidence of cerebrovascular events. The meta-analysis was performed with the
      fixed-effect model or random-effect model according to the heterogeneity.
      RESULTS: We retrieved ten studies enrolling a total of 1026 patients.
      Prophylactic NAC reduced the incidence of POAF (OR 0.56; 95% CI 0.40 to 0.77; P <
      0.001) and all-cause mortality (OR 0.40; 95% CI 0.17 to 0.93; P = 0.03) compared
      with controls, but failed to reduce the stay in ICU and overall stay in hospital.
      No difference in the incidence of cerebrovascular events was observed.
      CONCLUSIONS: Prophylactic use of NAC could reduce the incidence of POAF and all
      cause mortality in adult patients undergoing cardiac surgery. However, larger
      RCTs evaluating these and other postoperative complication endpoints are needed.

PMID- 24739516
TI  - Modeling mayhem: predicting invasion and proliferation kinetics in IDH1 mutant
      glioblastoma with mathematical models.

PMID- 24739517
TI  - Evaluation of anxiety-like behaviour in a rat model of acute postoperative pain.
AB  - BACKGROUND: Unrelieved acute postoperative pain can lead to a wide range of
      adverse effects, such as anxiety, depression, restlessness and sleep deprivation.
      OBJECTIVE: To investigate anxiety-like behaviour in a postoperative pain model.
      INTERVENTIONS AND MAIN OUTCOME MEASURES: Mechanical hypersensitivity was assessed
      with an electronic von Frey device, whereas anxiety-like behaviour was measured
      with light/dark testing and elevated plus maze testing. RESULTS: Rats developed
      significant mechanical hyperalgesia on 1, 3 and 8 days postsurgery compared with
      sham-operated rats. There was no reduction in motility between preincision and
      postincision when animals were allowed to move freely in an open field locomotion
      test. In light-dark tests, incised animals spent significantly less time than
      sham rats in the light compartment on the 1st and 3rd postoperative days.
      However, in an elevated plus maze test, differences between sham and incised rats
      were only observed on the 8th postoperative day as they spent significantly more
      time in the open arms. Pretreatment with morphine significantly increased
      withdrawal thresholds compared with treatment with saline (0.9% NaCl), but had no
      effect on light or open arm avoidance behaviour. CONCLUSION: We report that a rat
      model of acute postoperative pain is associated with anxiety-like increased light
      and open arm avoidance behaviour.

PMID- 24739518
TI  - Reply to: performance of videolaryngoscope and flexible fibreoptic endoscope in
      simulating difficult airways.

PMID- 24739519
TI  - Long-term inflammatory conditions following silicone exposure: the expanding
      spectrum of the autoimmune/inflammatory syndrome induced by adjuvants (ASIA).

PMID- 24739520
TI  - Alum, an aluminum-based adjuvant, induces Sjogren's syndrome-like disorder in
      mice.
AB  - OBJECTIVES: Adjuvant-induced innate immune responses have been suspected to play
      a role in the initiation of certain autoimmune disorders. This study investigates
      the role of alum, an aluminum-based adjuvant in the induction of Sjogren's
      syndrome-like disorder in mice. METHODS: Inbred, female New Zealand Mixed (NZM)
      2758 strain of mice were injected with alum. Control mice were treated similarly
      with PBS. The mice were monitored for salivary gland dysfunction by measuring
      pilocarpine-induced salivation. Presence of lymphocytic infiltrates within the
      submandibular glands was studied by histopathology. Autoantibodies to Ro and La
      proteins were analysed by ELISA and the presence of anti-nuclear antibodies (ANA)
      was analysed by indirect immunofluorescence. RESULTS: By eight weeks after
      treatment, the saliva production in the alum-treated mice was significantly
      decreased in comparison to the PBS-treated mice. This functional loss persisted
      till the termination of experiments at 20 wks. The incidence and severity of
      sialoadenitis was significantly higher in the alum-treated mice. Although there
      were no differences in the levels of anti-Ro/La autoantibodies in sera of alum
      and PBS-treated groups, the alum group showed higher ANA reactivity. CONCLUSIONS:
      In the NZM2758 mice, alum induces a Sjogren's syndrome-like disorder that is
      characterised by chronic salivary gland dysfunction and the presence of
      lymphocytic infiltrates within the salivary glands. Thus, the potential of
      aluminum-based adjuvants for induction of autoimmunity should be closely
      monitored in individuals genetically susceptible to developing autoimmune
      disorders.

PMID- 24739521
TI  - Autoimmune/inflammatory syndrome induced by adjuvants (ASIA) due to silicone
      implant incompatibility syndrome in three sisters.
AB  - Three sisters who carried the BRCA-1 gene mutation had a preventive mastectomy
      and were reconstructed with silicone breast implants. After the reconstruction
      all three patients developed fatigue, arthralgia, myalgia and sleep disturbances
      within a period of four years. Because the complaints were thought to be related
      to the silicone breast implants, they were advised to have the implants replaced
      by non-silicone gel containing Monobloc Hydrogel breast implants. After this
      replacement operation, all complaints improved as evaluated 2.5 years later.
      Since the complaints developed during the presence of silicone implants and since
      the reversal was observed after replacement by hydrogel implants we postulate
      that our patients suffered from ASIA due to silicone implants, i.e. Silicone
      Implant Incompatibility Syndrome (SIIS). The generation of this syndrome in three
      sisters suggests that the susceptibility to the development of SIIS may be
      genetically determined. 

PMID- 24739522
TI  - Mammalian orthoreovirus T3D infects U-118 MG cell spheroids independent of
      junction adhesion molecule-A.
AB  - In the canonical pathway, infection of cells by the wild-type mammalian
      orthoreovirus Type 3 Dearing (T3D) is dependent on the interaction of the viral
      spike protein sigma1 with the high-affinity cellular receptor junction adhesion
      molecule-A (JAM-A). We previously demonstrated that the human glioblastoma cell
      line U-118 MG does not express JAM-A and resists reovirus T3D infection in
      standard cell culture conditions (SCCC). Heterologous JAM-A expression sensitises
      U-118 MG cells to reovirus T3D. Here we studied reovirus infection in U-118 MG
      cells grown in spheroid cultures with the premise that cells in such cultures
      resemble cells in tumours more than those grown under standard adherent cell
      culture conditions on a plastic surface. Although the U-118 MG cells in spheroids
      do not express JAM-A, they are susceptible to reovirus T3D infection. We show
      that this can be attributed to factors secreted by cells in the spheroids. The
      concentration of active extracellular proteases cathepsin B and L in the medium
      of spheroid cultures was increased 19- and 24-fold, respectively, as compared
      with SCCC. These enzymes can convert the reovirus particles into a form that can
      infect the U-118 MG cells independent of JAM-A. Taken together, these data
      demonstrate that infection of tumour cells by wild-type reovirus T3D is not
      strictly dependent on the expression of JAM-A on the cell surface. 

PMID- 24739523
TI  - Prediction of inter-individual variability in the pharmacokinetics of CYP2C19
      substrates in humans.
AB  - Significant inter-individual variability of exposure for CYP2C19 substrates may
      be only partly due to genetic polymorphism. Therefore, the in vivo inter
      individual variability in hepatic intrinsic clearance (CL(int,h)) of CYP2C19
      substrates was estimated from reported AUC values using Monte Carlo simulations.
      The coefficient of variation (CV) for CL(int,h) in poor metabolizers (PM)
      expected from genotypes CYP2C19*2/*2, CYP2C19*3/*3 or CYP2C19*2/*3 was estimated
      as 25.8% from the CV for AUC of omeprazole in PMs. With this, CVs of CL(int,h) in
      extensive metabolizers (EM: CYP2C19*1/*1), intermediate metabolizers (IM:
      CYP2C19*1/*2 or *3) and ultra-rapid metabolizers (UM), CYP2C19*17/*17 and *1/*17,
      were estimated as 66.0%, 55.8%, 6.8% and 48.0%, respectively. To validate these
      CVs, variability in the AUC of CYP2C19 substrates lansoprazole and rabeprazole,
      partially metabolized by CYP3A4 in EMs and IMs, were simulated using the CV in
      CL(int,h) for CYP2C19 EMs and IMs and 33% of the CV previously reported for
      CYP3A4. Published values were within 2.5-97.5 percentile range of simulated CVs
      for the AUC. Furthermore, simulated CVs for the AUC of omeprazole and
      lansoprazole in ungenotyped populations were comparable with published values.
      Thus, estimated CL(int,h) variability can predict variability in the AUC of drugs
      metabolized not only by CYP2C19 but also by multiple enzymes.

PMID- 24739524
TI  - An ethnobotanical study of medicinal plants in high mountainous region of Chail
      valley (District Swat- Pakistan).
AB  - BACKGROUND: This paper represents the first ethnobotanical study in Chail valley
      of district Swat-Pakistan and provides significant information on medicinal
      plants use among the tribal people of the area. The aim of this study was to
      document the medicinal uses of local plants and to develop an ethnobotanical
      inventory of the species diversity. METHODS: In present study, semi-structured
      interviews with 142 inhabitants (age range between 31-75 years) were conducted.
      Ethnobotanical data was analyzed using relative frequency of citation (RFC) to
      determine the well-known and most useful species in the area. RESULTS: Current
      research work reports total of 50 plant species belonging to 48 genera of 35
      families from Chail valley. Origanum vulgare, Geranium wallichianum and Skimmia
      laureola have the highest values of relative frequency of citation (RFC) and are
      widely known by the inhabitants of the valley. The majority of the documented
      plants were herbs (58%) followed by shrubs (28%), trees (12%) and then climbers
      (2%). The part of the plant most frequently used was the leaves (33%) followed by
      roots (17%), fruits (14%), whole plant (12%), rhizomes (9%), stems (6%), barks
      (5%) and seeds (4%). Decoction was the most common preparation method use in
      herbal recipes. The most frequently treated diseases in the valley were urinary
      disorders, skin infections, digestive disorders, asthma, jaundice, angina,
      chronic dysentery and diarrhea. CONCLUSION: This study contributes an
      ethnobotanical inventory of medicinal plants with their frequency of citations
      together with the part used, disease treated and methods of application among the
      tribal communities of Chail valley. The present survey has documented from this
      valley considerable indigenous knowledge about the local medicinal plants for
      treating number of common diseases that is ready to be further investigated for
      biological, pharmacological and toxicological screening. This study also provides
      some socio-economic aspects which are associated to the local tribal communities.

PMID- 24739525
TI  - People-centred science: strengthening the practice of health policy and systems
      research.
AB  - Health policy and systems research (HPSR) is a transdisciplinary field of global
      importance, with its own emerging standards for creating, evaluating, and
      utilizing knowledge, and distinguished by a particular orientation towards
      influencing policy and wider action to strengthen health systems. In this
      commentary, we argue that the ability of the HPSR field to influence real world
      change hinges on its becoming more people-centred. We see people-centredness as
      recognizing the field of enquiry as one of social construction, requiring those
      conducting HPSR to locate their own position in the system, and conduct and
      publish research in a manner that foregrounds human agency attributes and values,
      and is acutely attentive to policy context. Change occurs at many layers of a
      health system, shaped by social, political, and economic forces, and brought
      about by different groups of people who make up the system, including service
      users and communities. The seeds of transformative practice in HPSR lie in
      amplifying the breadth and depth of dialogue across health system actors in the
      conduct of research - recognizing that these actors are all generators, sources,
      and users of knowledge about the system. While building such a dialogic practice,
      those conducting HPSR must strive to protect the autonomy and integrity of their
      ideas and actions, and also clearly explain their own positions and the value
      basis of their work. We conclude with a set of questions that health policy and
      systems researchers may wish to consider in making their practice more people
      centred, and hence more oriented toward real-world change. 

PMID- 24739526
TI  - Treatment options for symptomatic dural arteriovenous fistulas.

PMID- 24739527
TI  - Letter corresponding to the article 'insights into antibody-associated
      encephalitis' by Dr Merwick et al.

PMID- 24739528
TI  - Unc5C and DCC act downstream of Ctip2 and Satb2 and contribute to corpus callosum
      formation.
AB  - The pyramidal neurons of the mammalian neocortex form two major types of long
      range connections-corticocortical and cortico-subcortical. The transcription
      factors Satb2 and Ctip2 are critical regulators of neuronal cell fate that
      control interhemispheric versus corticofugal connections respectively. Here, we
      investigate the axon guidance molecules downstream of Satb2 and Ctip2 that
      establish these connections. We show that the expression of two Netrin1 receptors
      DCC and Unc5C is under direct negative regulation by Satb2 and Ctip2,
      respectively. Further, we show that the Netrin1-Unc5C/DCC interaction is involved
      in controlling the interhemispherical projection in a subset of early born, deep
      layer callosal neurons. 

PMID- 24739529
TI  - Micro-patterned surfaces reduce bacterial colonization and biofilm formation in
      vitro: Potential for enhancing endotracheal tube designs.
AB  - BACKGROUND: Ventilator-associated pneumonia (VAP) is a leading hospital acquired
      infection in intensive care units despite improved patient care practices and
      advancements in endotracheal tube (ETT) designs. The ETT provides a conduit for
      bacterial access to the lower respiratory tract and a substratum for biofilm
      formation, both of which lead to VAP. A novel microscopic ordered surface
      topography, the Sharklet micro-pattern, has been shown to decrease surface
      attachment of numerous microorganisms, and may provide an alternative strategy
      for VAP prevention if included on the surface of an ETT. To evaluate the
      feasibility of this micro-pattern for this application, the microbial range of
      performance was investigated in addition to biofilm studies with and without a
      mucin-rich medium to simulate the tracheal environment in vitro. METHODS: The top
      five pathogens associated with ETT-related pneumonia, Methicillin-Resistant
      Staphylococcus aureus (MRSA), Pseudomonas aeruginosa, Klebsiella pneumonia,
      Acinetobacter baumannii, and Escherichia coli, were evaluated for attachment to
      micro-patterned and un-patterned silicone surfaces in a short-term colonization
      assay. Two key pathogens, MRSA and Pseudomonas aeruginosa, were evaluated for
      biofilm formation in a nutrient rich broth for four days and minimal media for 24
      hours, respectively, on each surface type. P. aeruginosa was further evaluated
      for biofilm formation on each surface type in a mucin-modified medium mimicking
      tracheal mucosal secretions. Results are reported as percent reductions and
      significance is based on t-tests and ANOVA models of log reductions. All
      experiments were replicated at least three times. RESULTS: Micro-patterned
      surfaces demonstrated reductions in microbial colonization for a broad range of
      species, with up to 99.9% (p < 0.05) reduction compared to un-patterned controls.
      Biofilm formation was also reduced, with 67% (p = 0.12) and 52% (p = 0.05)
      reductions in MRSA and P. aeruginosa biofilm formation, respectively. Further, a
      58% (p < 0.01) reduction was demonstrated on micro-patterned surfaces for P.
      aeruginosa biofilms under clinically-simulated conditions when compared to un
      patterned controls. CONCLUSIONS: This engineered micro-pattern reduces the
      colonization and biofilm formation of key VAP-associated pathogens in vitro.
      Future application of this micro-pattern on endotracheal tubes may prevent or
      prolong the onset of VAP without the need for antimicrobial agents.

PMID- 24739530
TI  - Longterm follow-up in European respiratory health studies - patterns and
      implications.
AB  - BACKGROUND: Selection bias is a systematic error in epidemiologic studies that
      may seriously distort true measures of associations between exposure and disease.
      Observational studies are highly susceptible to selection bias, and researchers
      should therefore always examine to what extent selection bias may be present in
      their material and what characterizes the bias in their material. In the present
      study we examined long-term participation and consequences of loss to follow-up
      in the studies Respiratory Health in Northern Europe (RHINE), Italian centers of
      European Community Respiratory Health Survey (I-ECRHS), and the Italian Study on
      Asthma in Young Adults (ISAYA). METHODS: Logistic regression identified
      predictors for follow-up participation. Baseline prevalence of 9 respiratory
      symptoms (asthma attack, asthma medication, combined variable with asthma attack
      and/or asthma medication, wheeze, rhinitis, wheeze with dyspnea, wheeze without
      cold, waking with chest tightness, waking with dyspnea) and 9 exposure-outcome
      associations (predictors sex, age and smoking; outcomes wheeze, asthma and
      rhinitis) were compared between all baseline participants and long-term
      participants. Bias was measured as ratios of relative frequencies and ratios of
      odds ratios (ROR). RESULTS: Follow-up response rates after 10 years were 75% in
      RHINE, 64% in I-ECRHS and 53% in ISAYA. After 20 years of follow-up, response was
      53% in RHINE and 49% in I-ECRHS. Female sex predicted long-term participation (in
      RHINE OR (95% CI) 1.30(1.22, 1.38); in I-ECRHS 1.29 (1.11, 1.50); and in ISAYA
      1.42 (1.25, 1.61)), as did increasing age. Baseline prevalence of respiratory
      symptoms were lower among long-term participants (relative deviations compared to
      total baseline population 0-15% (RHINE), 0-48% (I-ECRHS), 3-20% (ISAYA)), except
      rhinitis which had a slightly higher prevalence. Most exposure-outcome
      associations did not differ between long-term participants and all baseline
      participants, except lower OR for rhinitis among ISAYA long-term participating
      smokers (relative deviation 17% (smokers) and 44% (10-20 pack years)).
      CONCLUSIONS: We found comparable patterns of long-term participation and loss to
      follow-up in RHINE, I-ECRHS and ISAYA. Baseline prevalence estimates for long
      term participants were slightly lower than for the total baseline population,
      while exposure-outcome associations were mainly unchanged by loss to follow-up.

PMID- 24739531
TI  - The balance beam metaphor: a perspective on clinical diagnosis.
AB  - Understanding the impact of clinical findings in discriminating between possible
      causes of a patient's presentation is essential in clinical judgment. A balance
      beam is a natural physical analogue that can accurately represent the combination
      of several pieces of evidence with varying ability to discriminate between
      disease hypotheses. Calculation of Bayes' theorem using log(posterior odds) as a
      function of log(prior odds) and the logarithms of the evidence's likelihood
      ratios maps onto the physical forces affecting objects placed on a balance beam.
      We describe the rules governing the functioning of tokens representing clinical
      findings in the comparison of 2 competing diseases. The likelihood ratios
      corresponding to positive (LR+) or negative (LR-) observations for each symptom
      determine the lateral position at which the symptom's token is placed on the
      beam, using a weight if the finding is present and a helium balloon if it is
      absent. We discuss how a balance beam could represent concepts of dynamic
      specificity (due to changes in competitor diseases' probabilities) and dynamic
      sensitivity (due to class-conditional independence). Utility-based thresholds for
      acting on a diagnosis could be represented by moving the balance beam's fulcrum.
      It is suggested that a balance beam can be a useful aid for students learning
      clinical diagnosis, allowing them to build on existing intuitive understanding to
      develop an appreciation of how evidence combines to influence degree of belief.
      The balance beam could also facilitate exploration of the potential impact of
      available questions or investigations.

PMID- 24739532
TI  - A balance beam aid for instruction in clinical diagnostic reasoning.
AB  - We describe a balance beam aid for instruction in diagnosis (BBAID) and
      demonstrate its potential use in supplementing the training of medical students
      to diagnose acute chest pain. We suggest the BBAID helps students understand the
      process of diagnosis because the impact of tokens (weights and helium balloons)
      attached to a beam at different distances from the fulcrum is analogous to the
      impact of evidence to the relative support for 2 diseases. The BBAID presents a
      list of potential findings and allows students to specify whether each is
      present, absent, or unknown. It displays the likelihood ratios corresponding to a
      positive (LR+) or negative (LR-) observation for each symptom, for any pair of
      diseases. For each specified finding, a token is placed on the beam at a location
      whose distance from the fulcrum is proportional to the finding's log(LR): a
      downward force (a weight) if the finding is present and a lifting force (a
      balloon) if it is absent. Combining the physical torques of multiple tokens is
      mathematically identical to applying Bayes' theorem to multiple independent
      findings, so the balance beam is a high-fidelity metaphor. Seven first-year
      medical students and 3 faculty members consulted the BBAID while diagnosing brief
      patient case vignettes. Student comments indicated the program is usable, helpful
      for understanding pertinent positive and negative findings' usefulness in
      particular situations, and welcome as a reference or self-test. All students
      attended the effect of the tokens on the beam, although some stated they did not
      use the numerical statistics. Faculty noted the BBAID might be particularly
      helpful in reminding students of diseases that should not be missed and
      identifying pertinent findings to ask for.

PMID- 24739534
TI  - Contributions of Second Opinions, Outcome Forecasts, and Testimonials to Patient
      Decisions about Knee Replacement Surgery.
AB  - BACKGROUND: Decision aids are now a well-established means of supporting patients
      in their medical decision making. The widespread use of decision aids invites
      questions about how their components contribute to patient decisions. OBJECTIVE:
      The objective of this study was to measure the importance of second opinions,
      patient-specific outcome forecasts, and patient testimonials relative to patient
      clinical and socioeconomic factors and the primary physician recommendation on
      the decision to undergo full knee replacement surgery to treat knee
      osteoarthritis. METHODS: Middle-aged and older members of the RAND American Life
      Panel (N = 1616) chose whether to recommend surgery as a treatment for each of 3
      hypothetical patients (vignettes) presented in a video-enhanced internet survey.
      Vignettes randomly sampled levels of scenario attributes. RESULTS: Second
      opinions, person-specific outcome forecasts, and 2 consistent patient
      testimonials strongly affected respondents' decision making; a single
      testimonial, however, did not significantly affect decisions. CONCLUSIONS:
      Information provided in a decision aid, including person-specific outcome
      forecasts and testimonials, can affect patient choices. The strong effect of
      testimonials and respondents' interest in reviewing them reinforces concerns
      about unwanted influence when testimonials are biased.

PMID- 24739533
TI  - Comparison of 4 Pediatric Health-Related Quality-of-Life Instruments: A Study on
      a Medicaid Population.
AB  - BACKGROUND: Few studies have compared multiple health-related quality-of-life
      (HRQOL) instruments simultaneously for pediatric populations. This study aimed to
      test psychometric properties of 4 legacy pediatric HRQOL instruments: the Child
      Health and Illness Profile (CHIP), the KIDSCREEN-52, the KINDL, and the Pediatric
      Quality of Life Inventory (PedsQL). METHODS: This study used data from 908
      parents whose children (ages 2-19 years) were enrolled in Florida Medicaid.
      Parents were asked via telephone interview to complete each instrument
      appropriate to the age of their children. Structural, convergent/discriminant,
      and known-group validities were investigated. We examined structural validity
      using confirmatory factor analyses. We examined convergent/discriminant validity
      by comparing Spearman rank correlation coefficients of homogeneous (physical
      functioning and physical well-being) versus heterogeneous (physical and
      psychological functioning) domains of the instruments. We assessed known-groups
      validity by examining the extent to which HRQOL differed by the status of
      children with special health needs (CSHCN). RESULTS: Domain scores of the 4
      instruments were not normally distributed, and ceiling effects were significant
      in most domains. The KIDSCREEN-52 demonstrates the best structural validity,
      followed by the CHIP, KINDL, and PedsQL. The PedsQL and the KIDSCREEN-52 show
      better convergent/discriminant validity than the other instruments. Known-groups
      validity in discriminating CSHCN versus no needs was the best for the PedsQL,
      followed by the KIDSCREEN-52, the CHIP, and the KINDL. CONCLUSION: No one
      instrument was fully satisfactory in all psychometric properties. Strategies are
      recommended for future comparison of item content and measurement properties
      across different HRQOL instruments for research and clinical use.

PMID- 24739535
TI  - The influence of disease risk on the optimal time interval between screens for
      the early detection of cancer: a mathematical approach.
AB  - The intervals between screens for the early detection of diseases such as breast
      and colon cancer suggested by screening guidelines are typically based on the
      average population risk of disease. With the emergence of ever more biomarkers
      for cancer risk prediction and the development of personalized medicine, there is
      a need for risk-specific screening intervals. The interval between successive
      screens should be shorter with increasing cancer risk. A risk-dependent optimal
      interval is ideally derived from a cost-effectiveness analysis using a validated
      simulation model. However, this is time-consuming and costly. We propose a
      simplified mathematical approach for the exploratory analysis of the implications
      of risk level on optimal screening interval. We develop a mathematical model of
      the optimal screening interval for breast cancer screening. We verified the
      results by programming the simplified model in the MISCAN-Breast microsimulation
      model and comparing the results. We validated the results by comparing them with
      the results of a full, published MISCAN-Breast cost-effectiveness model for a
      number of different risk levels. The results of both the verification and
      validation were satisfactory. We conclude that the mathematical approach can
      indicate the impact of disease risk on the optimal screening interval.

PMID- 24739536
TI  - Characteristics of Foot-and-Mouth Disease Viral Strains Circulating at the
      Wildlife/livestock Interface of the Great Limpopo Transfrontier Conservation
      Area.
AB  - Foot-and-mouth disease (FMD) inflicts severe economic losses within infected
      countries and is arguably the most important trade-restricting livestock disease
      in the world. In southern Africa, infected African buffaloes (Syncerus caffer)
      are the major reservoir of the South African Territories (SAT) types of the
      virus. With the progressive expansion of transfrontier conservation areas
      (TFCAs), the risk of FMD outbreaks is expected to increase due to a higher
      probability of buffalo/livestock contacts. To investigate the dynamics of FMD
      within and around the Great Limpopo TFCA (GLTFCA), 5 herds of buffaloes were
      sampled in June 2010 to characterize circulating viruses in South Africa and
      Zimbabwe. Three SAT-2 and three SAT-3 viral strains were isolated in both
      countries, including one that was genetically linked with a recent SAT-2 outbreak
      in Mozambique in 2011. In addition, two groups of unvaccinated cattle (n = 192)
      were serologically monitored for 1 year at the wildlife/livestock interface of
      Gonarezhou National Park (GNP) in Zimbabwe between April 2009 and January 2010,
      using the liquid-phase blocking ELISA (LPBE) and a test for antibodies directed
      against non-structural proteins (NSP). Neither clinical signs nor vaccination of
      cattle were reported during the study, yet a high proportion of the monitored
      cattle showed antibody responses against SAT-3 and SAT-1. Antibodies against NSP
      were also detected in 10% of the monitored cattle. The results of this study
      suggest that cattle grazing in areas adjacent to the GLTFCA can be infected by
      buffalo or other infected livestock and that cattle trade movements can act as
      efficient disseminators of FMD viruses to areas several hundred kilometres from
      the virus source. Current methods of surveillance of FMD at the GLTFCA interface
      seem insufficient to control for FMD emergence and dissemination and require
      urgent reassessment and regional coordination.

PMID- 24739537
TI  - Updated guidelines for management of high blood pressure in Japan.

PMID- 24739538
TI  - Efficacy and safety of 10-mg azilsartan compared with 8-mg candesartan cilexetil
      in Japanese patients with hypertension: a randomized crossover non-inferiority
      trial.
AB  - We investigated whether 10 mg per day of azilsartan, one-half of the normal
      dosage, would be non-inferior to 8 mg per day of candesartan cilexetil for
      controlling blood pressure in Japanese patients with hypertension. In this open
      label, randomized, crossover trial, 309 hypertensive Japanese adults treated with
      8-mg candesartan cilexetil were randomized into two arms and received either 10
      mg azilsartan or 8-mg candesartan cilexetil in a crossover manner. The primary
      efficacy outcome was systolic blood pressure, and the margin of non-inferiority
      was set to be 2.5 mm Hg. The participants were 67+/-11 years old, and 180 (58%)
      were male. The baseline systolic and diastolic blood pressure levels were 127.1+/
      13.2 and 69.7+/-11.2 mm Hg, respectively. During the study period, the difference
      in systolic blood pressure between the treatments with 10-mg azilsartan and 8-mg
      candesartan cilexetil was -1.7 mm Hg, with the two-sided 95% confidence interval
      (CI) ranged from -3.2 to -0.2 mm Hg. The upper boundary of the 95% CI was below
      the margin of 2.5 mm Hg, confirming the non-inferiority of 10-mg azilsartan to 8
      mg candesartan cilexetil. The difference also reached significance (P=0.037). The
      corresponding difference in diastolic blood pressure was -1.4 (95% CI: -2.4 to 
      0.4) mm Hg (P=0.006). Treatment with 10-mg azilsartan was similar to 8-mg
      candesartan cilexetil in its association with rare adverse events. In conclusion,
      10-mg azilsartan was non-inferior to 8-mg candesartan cilexetil for controlling
      systolic blood pressure in Japanese hypertensive patients already being treated
      with 8-mg candesartan cilexetil. 

PMID- 24739539
TI  - ANTXR2 is a potential causative gene in the genome-wide association study of the
      blood pressure locus 4q21.
AB  - Hypertension is the most prevalent cardiovascular disease worldwide, but its
      genetic basis is poorly understood. Recently, genome-wide association studies
      identified 33 genetic loci that are associated with blood pressure. However, it
      has been difficult to determine whether these loci are causative owing to the
      lack of functional analyses. Of these 33 genome-wide association studies (GWAS)
      loci, the 4q21 locus, known as the fibroblast growth factor 5 (FGF5) locus, has
      been linked to blood pressure in Asians and Europeans. Using a mouse model, we
      aimed to identify a causative gene in the 4q21 locus, in which four genes
      (anthrax toxin receptor 2 (ANTXR2), PR domain-containing 8 (PRDM8), FGF5 and
      chromosome 4 open reading frame 22 (C4orf22)) were near the lead single
      nucleotide polymorphism (rs16998073). Initially, we examined Fgf5 gene by
      measuring blood pressure in Fgf5-knockout mice. However, blood pressure did not
      differ between Fgf5 knockout and wild-type mice. Therefore, the other candidate
      genes were studied by in vivo small interfering RNA (siRNA) silencing in mice.
      Antxr2 siRNA was pretreated with polyethylenimine and injected into mouse tail
      veins, causing a significant decrease in Antxr2 mRNA by 22% in the heart.
      Moreover, blood pressure measured under anesthesia in Antxr2 siRNA-injected mice
      rose significantly compared with that of the controls. These results suggest that
      ANTXR2 is a causative gene in the human 4q21 GWAS-blood pressure locus.
      Additional functional studies of ANTXR2 in blood pressure may identify a novel
      genetic pathway, thus increasing our understanding of the etiology of essential
      hypertension. 

PMID- 24739540
TI  - Impact of global risk assessment on the evaluation of hypertensive patients
      treated by primary care physicians in Korea (a Nation-Wide, Multi-Center,
      Observational, Cross-Sectional, Epidemiologic Study to Evaluate the Proportion of
      Cardiovascular Risk Factors in Korean hypertensive patients: WONDER study).
AB  - Global cardiovascular risk evaluation and stratification is essential to identify
      high-risk hypertensive patients. However, it is uncertain how often the strategy
      is executed in real clinical practice. We sought to evaluate whether global risk
      evaluation might change the risk stratification in Korean hypertensive patients
      treated by primary care physicians. A total of 3109 hypertensive patients were
      analyzed. The mean age was 62.3+/-11.3 years, and 1502 (48.3%) of the
      participants were male. The global risk evaluation revealed that 1862 patients
      (59.9%) were classified as having high- or the very high-risk. High-risk patients
      were older and obese, and had a male predominance, a longer duration of
      hypertension and a low HDL-cholesterol. The systolic and diastolic blood
      pressures (BP) were significantly higher in the high-risk group (P<0.0001).
      However, combination antihypertensive therapy was more common in the low-risk
      group (P=0.0265). A total of 2155 patients (69.3%) were reclassified into the
      higher or the lower-risk group by performing additional tests. In a multivariate
      logistic regression analysis, age, body mass index, BP, metabolic syndrome, left
      ventricular hypertrophy and chronic kidney disease were independent factors
      associated with risk reclassification with global risk evaluation. In conclusion,
      although the majority of hypertensive patients treated by the primary care
      physicians were in the high- or very high-risk group, their risk levels were not
      appropriately stratified. However, simple additional tests enhanced the risk
      evaluation of hypertensive patients. Accordingly, comprehensive cardiovascular
      risk stratification should be undertaken in all hypertensive patients. 

PMID- 24739541
TI  - Significance of white-coat and masked hypertension in chronic kidney disease and
      end-stage renal disease.
AB  - Hypertension is a frequent and modifiable cardiovascular risk factor with a
      cyclic relationship with chronic kidney disease (CKD). The diagnosis, treatment,
      monitoring and control of high blood pressure are all mandatory not only in CKD
      but also in end-stage renal disease (ESRD). As demonstrated by studies using
      population and hypertensive patients, white-coat hypertension (WCHT) and masked
      hypertension (MHT) carry a particular degree of risk. The advantages of
      ambulatory techniques in the management and prognostic stratification of patients
      with CKD and ESRD have also been recognized. However, most of the evidence
      underlines the importance of nocturnal hypertension and neglects WCHT and MHT.
      The absence of specific reports involving untreated and treated patients hinders
      the ability to significantly discriminate WCHT from the white-coat effect and MHT
      from masked uncontrolled hypertension. The heterogeneous definitions that are
      used add additional difficulty in translating experimental evidence into clinical
      practice. Reaching a consensus in definitions is mandatory for designing future
      research. Cross-sectional studies underscore the frequency of misdiagnosis,
      potentially leading to undertreatment (MHT) and overtreatment (WCHT) in renal
      disease. The divergent prevalence of WCHT and MHT reported in CKD could be
      related to the diverse definitions of hypertension and the heterogeneity of the
      pathologies pooled under the CKD definition. Even in the absence of randomized
      clinical trials specifically addressing this issue, the scarce longitudinal
      studies confirm that WCHT carries a risk close to that of sustained normotension,
      whereas MHT is associated with a risk close or identical to that of sustained
      hypertension. 

PMID- 24739542
TI  - Use of ambulatory blood pressure measurement in the definition of resistant
      hypertension: a review of the evidence.
AB  - Resistant hypertension as defined by the European Society of Hypertension and
      American Heart Association is a blood pressure that remains uncontrolled despite
      concomitant intake of at least three antihypertensive drugs (one of them
      preferably being a diuretic) at full doses. This definition is still based on
      office rather than out-of-office blood pressure measurement. In this review we
      propose a new, stricter definition of resistant hypertension based on ambulatory
      blood pressure measurement. The main arguments in favor of this are: (1) in
      patients with resistant hypertension, ambulatory blood pressure is an independent
      predictor of cardiovascular morbidity whereas, after adjustment for conventional
      risk factors, conventional blood pressure has little added value; (2) white-coat
      resistant hypertension (uncontrolled office with normal ambulatory blood
      pressure) is frequent (30-40% of patients with apparently resistant hypertension)
      carrying a prognosis similar to that of controlled hypertension, and
      intensification of blood pressure lowering treatment, or the use of nondrug
      treatment strategies such as renal denervation or carotid baroreceptor
      stimulation, is not justified; (3) masked resistant hypertension (controlled
      office with elevated ambulatory blood pressure) is frequent (approximately one
      third of patients with controlled office blood pressure on triple
      antihypertensive therapy) and associated with an increased risk of cardiovascular
      events; in such patients, treatment intensification should be considered; (4) the
      current definition of resistant hypertension (office blood pressure ? 140/90 mm
      Hg on triple antihypertensive therapy) allows a substantial proportion of
      patients with spurious or white-coat resistant hypertension to undergo renal
      denervation in the absence of proven long-term benefits.

PMID- 24739543
TI  - Temperature dependence of resistive switching behaviors in resistive random
      access memory based on graphene oxide film.
AB  - We reported resistive switching behaviors in the resistive random access memory
      (RRAM) devices based on the different annealing temperatures of graphene oxide
      (GO) film as active layers. It was found that the resistive switching
      characteristics of an indium tin oxide (ITO)/GO/Ag structure have a strong
      dependence on the annealing temperature of GO film. When the annealing
      temperature of the GO film was 20  degrees C, the devices showed typical write
      once-read-many-times (WORM) type memory behaviors, which have good memory
      performance with a higher ON/OFF current ratio (~10(4)), the higher the high
      resistance state (HRS)/low resistance state (LRS) ratio (~10(5)) and stable
      retention characteristics (>10(3) s) under lower programming voltage (-1 V and 
      0.5 V). With the increasing annealing temperature of GO film, the resistive
      switching behavior of RRAM devices gradually weakened and eventually disappeared.
      This phenomenon could be understood by the different energy level distributions
      of the charge traps in GO film, and the different charge injection ability from
      the Ag electrode to GO film, which is caused by the different annealing
      temperatures of the GO film. 

PMID- 24739545
TI  - [Evaluation on the efficacy of prevention programs and relevant factors targeting
      mother-to-infant transmission on hepatitis B virus in Yunnan province].
AB  - OBJECTIVE: To explore the efficacy of prevention programs and relevant factors
      targeting mother-to-infant transmission of HBV in Yunnan province. METHODS: In
      Yunnan province, we selected HBsAg positive pregnant women that delivered in
      hospital from January 1st through June 30th, 2011. Newborns of these pregnant
      women were under PMTCT (prevention of mother to child treatment) program and
      followed. Every infant was drawn 2 ml venous blood and questionnaire survey was
      carried out when the baby was 7-12 month-old and completed the vaccination
      processes. Serum samples of them were then collected and detected on the 5
      serological indicators of HBV. RESULTS: were analyzed statistically. RESULTS:
      There were 2 765 infants in the study program. The success rate of PMTCT was
      95.88% . Rates of coverage on both timely-birth dose and 3 doses of HepB were
      97.03% and 92.30% respectively. The overall vaccinated rate and timely-birth
      vaccinated rate on hepatitis B immunoglobulin (HBIG) were 68.97% and 94.49%
      respectively. The success rate of PMTCT was 97.16% after administration of
      passive-active immune-prophylaxis (HepB and HBIG), compared to the rate as 93.01%
      when vaccinated with HepB only. Significant differences were seen in the
      successful rates of PMTCT between combined and non-combined immunization. Either
      the combined or non-combined immunization, there were significant differences
      seen in the success rates of PMTCT regardless the positivity status of HBsAg or
      HBeAg, among the infected mothers. CONCLUSION: The efficacy of passive-active
      immune-prophylaxis program seemed to be better than the one without combined
      immunization. It was vitally important for the infants whose mothers' HBsAg and
      HBeAg status were positive, to receive regular and timely combined immunization.
      In order to promote the PMTCT in Yunnan province, vaccinated rate on HBIG should
      be further improved.

PMID- 24739544
TI  - [Study on the spatial and temporal distribution of animal plague in Junggar Basin
      plague focus].
AB  - OBJECTIVE: To explore the spatial and temporal distributions of animal plague in
      Junggar Basin natural plague focus. METHODS: Data regarding plague antibody (F1)
      in serum of Great Gerbil (Rhombomys opimus, R. opimus) which were collected from
      2005 to 2012 in Junggar Basin and analyzed. The changing rates on the positivity
      of F1 that appeared spatially and temporally were also analyzed. RESULTS: A total
      of 4 825 R. opimus serum samples were collected in 13 administrative regions in
      Junggar Basin. RESULTS: showed that plague R. opimus existed in two areas
      Gurbantonggut desert in the eastern-center and the clay desert of western Junggar
      Basin. However, in these two areas, the intensity of animal plague prevalence was
      different. In the former region where Yesinia pestis positive serum was detected
      from R. opimus, the detected rate of R. opimus was 8.39%. However, in the latter
      areas, the average positive rate was 1.56%. The changing trends of R. opimus
      plague prevalence were also varied annually. In the western Junggar Basin, the
      trend showed a slowly downward profile. The serum positive rate of R. opimus for
      Yesinia pestis decreased, from 7.59% in 2005 to 0.61% in 2008, and appeared as a
      resting state that none of the positive sample could be found since then.
      However, in the eastern-center Junggar Basin area-also named as Gurbantonggut
      desert which had been divided into 3 segments(western, central and eastern,
      according to related geographical characteristics), the changing trends of animal
      plague seemed quite complex. In the western segment, the animal plague had two
      epidemic peaks-in 2006 and 2010, with the interval of 4 years, with the higher
      peak of all the three geographic segments as 45.65% in 2010 and the positive
      serum of R. opimus for plague could be detected each year from 2006 to 2012.
      However, there were 3 epidemic peaks in the same period in the central and
      eastern segments. In the central segment, the peaks appeared in 2006, 2009 and
      2011, with the intervals as 2.5 years and the average positive rate 8.92% was
      seen the lowest in Gurbantonggut desert. In the eastern segment, the first 2
      peaks appeared the same season as in the central segment, but the third peak
      appeared in 2012, with the peak interval as 3 years. The positive rate of R.
      opimus for plague was also different in seasons, with the positive rate higher in
      autumn than in spring. These findings showed that the animal plague could be
      continuously prevalent from spring to autumn in the natural foci of plague in the
      Junggar Basin. CONCLUSION: Both geographical and temporal fluctuations of animal
      plague existed in the natural foci of Junggar Basin which was also named as
      geographical heterogeneity. Consequently, animal plague could be divided into two
      areas-the clay plains desert in the western and the Gurbantonggut desert in the
      eastern-center Junggar Basin.

PMID- 24739546
TI  - [Study on the relationship between semen HBV-DNA load and offspring-paternal
      vertical- transmission of HBV].
AB  - OBJECTIVE: To explore the relationship between HBV-DNA load and the offspring
      vertical transmission of HBV. METHODS: 138 families who had taken the examination
      between August 2009 and November 2011 but the HBsAg of the housewife was
      negative, were chosen as research objects. Blood from the couples and sperms from
      the husbands during pregnancy were followed and collected for detection on
      related indicators. Cord blood was sampled after delivery for HBVM and HBV-DNA
      quantification. Those with HBV-DNA load >=5*10(2) copies/ml were chosen as cases
      while those <5 * 10(2) copies/ml were formed as controls, respectively. RESULTS:
      1) The positive rates of HBV-DNA was 34.8% (48/138)in the neonatal cord blood
      while the positive rates of cord blood HBsAg and HBeAg were 28.3% (39/138) and
      15.2% (21/138) respectively. 2) The positive rate of semen HBV-DNA was 21.0%
      (29/138) while the positive rates of paternal serum HBV-DNA and HBeAg were 76.8%
      (106/138) and 42.8% (59/138). 3) Among the positive ones on paternal serum HBV
      DNA, paternal serum HBeAg, semen HBV-DNA, items as measures taken for HBV
      vertical transmission and prevention on the fathers and the first class family
      histories on HBV appeared to be the risk factors for HBV paternal transmission (P
      < 0.05). 4) Data from Multivariate analysis showed that positivities on paternal
      serum HBV-DNA, paternal serum HBeAg and semen HBV-DNA were risk factors for HBV
      paternal transmission (OR = 5.7, 95%CI:1.1-29.1; OR = 4.2, 95%CI:1.7-10.0; OR =
      6.7, 95% CI:2.4-18.9). 5)Dose-response relationships were seen between levels of
      paternal serum HBV-DNA load and cord blood HBV-DNA load, between levels of
      paternal serum HBV-DNA load and semen HBV-DNA load, between levels of semen HBV
      DNA load and cord blood HBV-DNA load. 6)Results from the analysis on ROC curve
      showed that paternal serum HBV-DNA load level (10(5) copies/ml)and semen HBV-DNA
      load level (10(3) copies/ml) were better demarcation points to forecast the
      occurrence of paternal transmission of HBV, because of the better sensitivity and
      specificity they had. CONCLUSION: Items as positives on paternal serum HBV-DNA,
      paternal serum HBeAg and semen HBV-DNA were risk factors for HBV paternal
      transmission. When paternal serum HBV-DNA load >10(5) copies/ml and semen HBV-DNA
      load >10(3) copies/ml appeared, the positive rate of HBV paternal transmission
      would increase.

PMID- 24739547
TI  - [Study on the characteristics of serology and sexual behavior among drug users at
      the HIV sentinel surveillance sites in 2012].
AB  - OBJECTIVE: To analyze the serological results and sexual behavior among different
      types of drug users (DUS) at the HIV sentinel surveillance sites. METHODS:
      Sentinel surveillance programs were conducted between April and June annually.
      DUS were those involved in custodes, living at the communities and those
      attending the methadone maintenance treatment clinics but with positive urine
      tests one month before blood sampling collected and questionnaire survey started.
      RESULTS: 116 279 drug abusers were included in the analysis. The prevalence rates
      of HIV, Syphilis and HCV among traditional drug (heroin, etc.)users were 5.0%,
      4.4% and 49.4%, while the prevalence rates of new narcotic (meth, etc.) users
      were 0.5%, 4.6%, 15.2%, respectively. The prevalence rates of HIV, syphilis among
      traditional drug uses were higher than the new narcotic users (P < 0.01). The
      proportion of sexual behavior in last month and the proportion of sexual behavior
      with casual and commercial sexual partners were 46.3%, 87.2% and 28.1% among the
      new narcotic users, respectively, which were higher than those among traditional
      drug users (40.7% , 82.8% and 22.2%). The proportion of using condom in last
      sexual contact with casual sexual partner was 33.3% among the new narcotic users
      which was less than traditional drug users (36.2%). The proportion of condom use
      in the last commercial sexual contact was 65.1% which was higher than those
      traditional drug users (62.9%). The proportion of never using condom with casual
      and commercial sexual partners in the past year was 43.2% and 19.0% among the
      traditional drug users, which were higher than those among new narcotic users
      (41.3%, 15.3%). CONCLUSION: Compared with the traditional drug abusers, the
      sexual behavior of new narcotic users seemed more active, less engaging in condom
      use but with higher risk of HIV transmission through sexual contact.

PMID- 24739548
TI  - [Descriptive epidemiological study on mental disabilities in China].
AB  - OBJECTIVE: To describe the prevalence and characteristics of mental disabilities
      in China. METHODS: The data from the Second National Sample Survey on Disability
      were analyzed with descriptive epidemiological method and the overall prevalence
      rates of mental disabilities were statistically calculated. RESULTS: Among 2 526
      145 respondents, 15 155 of them more than 15 years old were diagnosed as mental
      disabilities, with the prevalence rate as 6.010/00. The prevalence rate of
      disabilities caused only by mental disorders was 4.570/00 with 11 501 more than
      15 years old. The prevalence rate of disability caused only by mental disorders
      was 4.670/00 with 11 501 adults. Of the disability cases that exclusively caused
      by mental disorders, 64.58% of them were attributable to schizophrenia,
      schizotypal or delusional disorders, 6.28% were mood disorder, and 6.27% were
      epilepsy disability, followed by neurotic, stress-related and somatoform
      disorders (5.95%), dementia (5.19%), and other disabilities (less than 11.74%).
      Disabilities that attributable to schizophrenia, schizotypal and delusional
      disorders caused most severe impairments of functions in daily and social
      activities, followed by disabilities attributable to dementia, non-dementia
      organic mental disorder and epilepsy disability. Dementia caused the most severe
      grade of disability, accounted for 44.89% of all the cases. The data also showed
      that the disabilities attributable to mood disorder and neurotic, stress-related
      and somatoform disorder showed more impairments among mental disabilities.
      CONCLUSION: Prevalence of mental disability in the second sample survey was
      higher than that of the first survey. Schizophrenia accounted for most of the
      mental disabilities but dementia caused the severest disability among all the
      cases with mental problems. As two of main causes of mental disabilities,
      neurosis and anxiety disorders should also be paid attention to.

PMID- 24739549
TI  - [Relations between problems on sleeping and suicidal behaviors in middle school
      students].
AB  - OBJECTIVE: To understand the epidemiological characteristics and possible
      associations between sleeping problems and suicidal behaviors among middle school
      students. METHODS: A total of 13 817 middle school students were selected in
      Shenyang,Xinxiang, Chongqing and Guangzhou cities and cluster sampling method was
      used. Questionnaires would include information on demographics, quality of sleep,
      psychopathological status and suicidal behaviors. Pittsburgh Sleep Quality index
      (PSQI) and Adolescent Multidimensional Sub-health Questionnaire (MSQA) were used
      to assess the quality of sleep and psychosomatic symptoms, respectively. Rates on
      sleeping problems and suicidal behaviors were compared in students with specific
      characteristics. Effects related to sleeping problems and suicidal behaviors were
      analyzed, using the multivariate logistic regression model. RESULTS: The overall
      prevalence of problems related to sleeping among middle school students was
      26.5%. 28.2% of the girls and 35.2% of senior students reported as having more
      sleeping problems. Rates on suicide related ideation, planning and attempts were
      16.6%, 9.6% and 4.7% , respectively. Girls reported more suicide ideation than
      boys. However, no gender differences were found in suicide planning or attempted
      suicide. It also suggested that the incidence of the suicidal behavior among
      students with sleeping problems was significantly higher than students without
      sleeping problems. Data from Multivariable logistic regression analysis showed
      that sleeping problems appeared as independent risk factors on suicidal behavior.
      Higher PSQI scores seemed coincide with the increased risk of suicidal behaviors.
      Students having sleeping time less than 5 hours per day showed higher risk of
      suicidal behaviors. CONCLUSION: Problems on sleeping seemed a strong risk factor
      for suicidal behaviors among middle school students. Improvement on the quality
      of sleep and reasonable arrangement of sleeping time could help prevent related
      suicidal behaviors among middle school students.

PMID- 24739550
TI  - [Influence of mediating/moderating effects of health skills on the relation
      between knowledge and behaviors in health, among college students].
AB  - OBJECTIVE: To study the influence of mediating/moderating effects of health
      skills on the relations between health knowledge and health behaviors in college
      students. METHODS: Stratified cluster random sampling was used among 2 181
      students, selected in several colleges in Changsha, Hunan province. EpiData 3.0
      was adopted to establish the database. Correlation and regression analyses were
      performed by SPSS 17.0. RESULTS: Positive correlations were seen on: 1) Knowledge
      and skills on health (r = 0.592, P < 0.01), 2) Knowledge and behaviors on health
      (r = 0.647, P < 0.01), 3) Health skills and health behaviors(r = 0.629, P <
      0.01). The mediating effect of health skills on the relations between health
      knowledge and health behaviors was significant (34.55%). The interaction effect
      of "health skill * (times) related knowledge" was significant (beta = -0.093, t =
      - 5.212, P = 0.000). New variables that were produced by the interaction also
      reached significant level (Delta R(2) = 0.006, P = 0.000), resulted in increasing
      the explanation function to health behaviors by 0.6%. CONCLUSION: Health skills
      could partially mediate the effects and moderate the relationship between health
      knowledge and health behaviors among college students.

PMID- 24739551
TI  - [Analysis on the relations between levels of change and the mental decisive
      factors on the physical exercise behavior among middle school students].
AB  - OBJECTIVE: To study the situation of sports and its influencing factors among
      students in order to improve health related education and promotion programs.
      METHODS: A multistage random sampling method was used on 3 600 students from
      three cities to understand their physical exercise behavior. Both t and chi(2)
      test were used to measure the scale of psychology and to describe the time spent
      on exercise. Single variance factor was used to measure the levels of change on
      behavior of physical activities, psychological and physical exercise behaviors.
      RESULTS: The weekly exercise time for students was 2.66 +/- 1.801 days, with
      81.4% of the students less than four days. Data showed that 37.3%, 23.6%, 20.5%
      of the high school students were in pre-contemplation stage, in contemplation
      stage, or in preparation stage respectively, with only 18.6 percent of the high
      school students in the action phase and maintaining phase. Students in the stages
      of change increase the amount of physical exercises. Scores with statistically
      significant differences were seen in the following areas: between five stages of
      behavior change on strategies (F = 77.442, P < 0.001), forward effects on the
      balance of decision-making (F = 29.498, P < 0.001), having negative effects (F =
      14.784, P < 0.001)and self-efficacy (F = 135.544, P < 0.001). Changing strategy
      on the intention stage of front maintenance phase, positive effects on decision
      making balance and self-efficacy scores were increasing along with the increasing
      stages of changing. The effect of balancing the negative effects increased when
      the change of phase decreased. CONCLUSION: Students were in lack of physical
      exercise per week. The differences related to the behavior on physical exercise
      did exist but most of the high school students were in the primary stage.
      Psychological factors played important role in the different stages of changing,
      suggesting that high school students should receive different health education
      and psychological intervention measures to enhance the effectiveness of physical
      exercise.

PMID- 24739552
TI  - [A cross-sectional survey on behavior problems among eco-migrant children of Hui
      and Han in Ningxia, China].
AB  - OBJECTIVE: To investigate the detection rate and correlates of behavioral
      problems among eco-migrant children in Hui and Han ethnicities. METHODS: Using
      multistage randomized sampling method, 2 653 eco-migrant teenagers, 3 174
      indigenous and 2 334 homeland peers were selected. Their parents were asked to
      finish the Achenbach's Child Behavior Checklist (CBCL) and a self-developed
      correlates questionnaire. RESULTS: 765 eco-migrant children with behavioral
      problems were detected, with detection rate as 28.8%, higher than that of
      homeland group (24.2%) and native group (19.3%) (chi(2) = 73.547, P < 0.012 5).
      Ecological migration mainly influenced factors as bad contacts, depression,
      obsessive-compulsive, discipline, attack for boys aged 6-11, bad contacts for
      boys aged 12-16 and extraversion behavioral problems for girls aged 12-16, in
      Hui. These factors both associated to eco-migrant children's behavioral problems
      in Hui and Han:cesarean section (OR = 1.863, 95% CI:1.144-3.035, for Han) and (OR
      = 2.979, 95% CI:2.067-4.293, for Hui), physical defects (OR = 1.730, 95%CI:1.087
      2.751, for Han) and (OR = 2.552, 95%CI:1.649-3.950, for Hui), arable as a main
      income way(OR = 1.272, 95%CI:1.066-1.518, for Han) and (OR = 1.212, 95%CI: 1.033
      1.422, for Hui), parents' education level above middle school (OR = 0.709, 95%
      CI: 0.539-0.932, for Han) and (OR = 0.698, 95%CI: 0.542-0.898, for Hui), parents'
      frequently in good mood (OR = 0.710, 95%CI:0.613-0.821, for Han) and (OR = 0.826,
      95%CI:0.718-0.949, for Hui). However, major diseases in the process of growth (OR
      = 1.794, 95% CI:1.163-2.767), and parents with chronic illness or disability (OR
      = 1.463, 95% CI:1.061-2.016) only associated with that in Han;single-parent or
      remarried families(OR = 1.583, 95% CI:1.078-2.325), parents often drinking (OR =
      1.557, 95%CI:1.019- 2.379), the time of parents' work longer than half a year (OR
      = 1.494, 95% CI:1.197-1.864), parents' more content to life now(OR = 0.813, 95%
      CI:0.700-0.945), and children in older age (OR = 0.939, 95%CI:0.889-0.991) only
      related to that in Hui. CONCLUSION: The eco-migrant children showed a low state
      in mental health, especially among Hui peers, and the correlated factors were
      different in Han and Hui, which was supposed to get great importance when taking
      effective intervention.

PMID- 24739553
TI  - [Association between socioeconomic status and esophageal squamous cell carcinoma
      in the population of Taixing area, Jiangsu province].
AB  - OBJECTIVE: To study the relationship between socioeconomic status (SES) and
      esophageal squamous cell carcinoma (ESCC) in Taixing city,Jiangsu province.
      METHODS: A population-based case-control study was carried out to collect data
      including demography, socioeconomic status indicators and possible risk factors.
      Unconditional logistic regression was used to compare different SES indicators
      and composite wealth scores constructed between cases and controls, using the
      principal component analysis methodology. RESULTS: Factors as:having received
      high school or higher education (OR = 0.66, 95% CI:0.46-0.96), living space over
      67 m2 per-capita (OR = 0.71, 95% CI: 0.54-0.94), drinking tap water longer than 5
      years (OR = 0.76, 95% CI:0.59-0.98) and wealth score >0.93 (OR = 0.63, 95%CI:0.48
      0.83)were associated with increased risk of ESCC. Compared to those worked in
      farming, forestry, animal husbandry, fishery and water conservancy, the
      individuals who worked in business-service industry were at lower risk of ESCC(OR
      = 0.65, 95%CI:0.43-0.97). CONCLUSION: An inverse association of low SES and ESCC
      were found in Taixing people that called for further explanation.

PMID- 24739554
TI  - [Spatial analysis on the HIV/AIDS infection status among injecting drug users in
      China, from 2005 to 2011].
AB  - OBJECTIVE: To analyze the spatial distribution of HIV/AIDS epidemics among
      injecting drug users(IDUs) in China from 2005 to 2011 and to understand its
      changing trend. METHODS: Using data on people living with HIV and AIDS through
      injecting drug between 2005 and 2011 to analyze the demographic characteristics
      of injecting drug users. Analysis on spatial correlation (provincial level and
      country level) and median center of hot spots(country level)were conducted by
      Arcgis software. RESULTS: Sex ratio (male/female) and registered place
      ratio(province/other provinces)reduced as time went by, with the ratios in 2011
      as 6.75 and 7.01 respectively. Tape ratio of the disease between HIV and AIDS
      showed an upward trend (Z = 26.880, P < 0.01). Since 2005, the identified numbers
      of HIV/AIDS and the spatial correlation and hot spots in provincial level had
      reduced, the numbers of provincial hot spots were two from 2009 to 2011(Sichuan
      and Yunnan provinces)at the national level. However, the spatial correlation and
      hot spots at the provincial level had an increasing trend. Between 2005 and 2011,
      the Western Median Centers of hot spots was located in Xinjiang province while
      the Southwestern Median Center of hot spots tended to move towards the north.
      CONCLUSION: The demographics changes of HIV/AIDS infection among injecting drug
      users seemed to be regular from 2005 to 2011. Spatial correlation at the
      provincial level was reducing. However, the spatial correlation and the numbers
      of hot spots at the country level increased, with hot spots at the country level
      tended to move from the border areas towards inland.

PMID- 24739555
TI  - [Study on norovirus GII.4/Sydney 2012 variant in China].
AB  - OBJECTIVE: To study the nucleotide and amino acid sequences of norovirus G
      II.4/Sydney 2012 variants, in China. METHODS: Twenty-two stool specimens,
      confirmed as G II.4/Sydney 2012- positive were collected from Beijing in the
      winter of 2012-2013. RT-PCR was performed to target the complete capsid gene. G
      II.4/Sydney 2012 strains from other regions in China were searched and obtained
      from the GenBank. Nucleotide and amino acid sequences of G II.4/Sydney 2012
      strains were analyzed, using the CLUSTAL X(Version 1.83)and followed by
      phylogenetic analysis using Mega version 5.1. RESULTS: The complete major capsid
      nucleotide sequences of thirty-eight G II.4/ Sydney 2012 strains from seven
      regions in China were obtained. The VP1 nucleotide and amino acid sequences
      diversity were 0.1%-3.3% and 0-3.1%, respectively. Result from phylogenetic
      analysis demonstrated that the G II.4/Sydney 2012 variant shared a common
      ancestor with both the dominant norovirus G II.4 variants Apeldoorn 2008 and the
      New Orleans 2009. G II.4/Sydney 2012 variants appeared to have had two A/D/E site
      combinations at the amino acid level, TSRN-GTT-SNT and TSRN-STT-SNT. CONCLUSION:
      G II.4/Sydney 2012 variant had been circulating in many regions in China. There
      seemed a high nucleotide and amino acid identity among G II.4/Sydney 2012 strains
      collected from China. G II.4/Sydney 2012 variants showed different A/D/E site
      combination from other pandemic G II.4 variants.

PMID- 24739556
TI  - [Validation on the elimination of neonatal tetanus programs through Lot Quality
      Assurance-Cluster Sample Survey in China].
AB  - OBJECTIVE: Field surveys were performed under WHO recommended validation
      procedures, using the Lot Quality Assurance-Cluster Sample(LQA-CS)method to
      validate the elimination status regarding neonatal tetanus in China. METHODS: LQA
      CS surveys were conducted in two areas under the highest risk of neonatal tetanus
      Jiangmen prefecture in Guangdong and Hechi in Guangxi. Random sampling method was
      conducted on 96 survey clusters in each prefecture with 12 eligible live
      births(live birth born one year before the survey)for each cluster, by trained
      investigators. RESULTS: There were 1 153 eligible live births from 23 465
      families surveyed in Jiangmen and 1 152 eligible live births from 21 623 families
      being studied in Hechi. All the indices on quality control were strictly
      followed. There was no neonatal tetanus case which met the criteria of neonatal
      elimination found in either of the areas. Data showed that neonatal tetanus had
      been eliminated in both Jiangmen and Hechi cities. CONCLUSION: Since both
      Jiangmen and Hechi were cities having the highest-risk in China, it was most
      likely that neonatal tetanus had also been eliminated in other prefectures at
      lower risk. Elimination programs on MNT was therefore considered validate in
      China when the study was carried out. However, the achievements needed to be
      maintained.

PMID- 24739557
TI  - [Current infection status and epidemic risk analysis of Dengue fever and
      Chikungunya in Guangdong province, from 1990 to 2012].
AB  - OBJECTIVE: To understand the status of infection and epidemic trend of Dengue
      fever and Chikungunya in Guangdong. METHODS: Retrospective survey and literature
      review were used to obtain data on the incidence, etiology of Dengue and
      Chikungunya. Serological survey was conducted to detect the specific-antibodies
      in healthy individuals for both Dengue virus(DENV)and Chikungunya virus (CHIKV).
      RESULTS: Three epidemics of Dengue fever were observed during 1990-2012, with the
      annual incidence rates as 9.75/100 000 in 1995, 1.76/100 000 in 2002 and 1.25/100
      000 in 2006, respectively. The predominant epidemic strains appeared to be DENV-2
      and DENV-4 during 1990-1994. Since 1995,DENV-1 had become the predominant
      transmission strain which lasted for almost 13 years. Co-existence of multiple
      serotypes of DENV started in 2009. Of the 7 718 sera from healthy population
      during 2003-2012, 180 specimens were detected positive for specific DENV-IgG
      antibody, ended with a sero-prevalence rate of 2.33%. All 2 132 sera in 2012 were
      detected negative for CHIKV-IgG antibody. CONCLUSION: The overall exposure level
      to Dengue was considered to be low in Guangdong province. However, the
      predominant transmission mode caused by DENV-1 had been gradually changed into
      the co-existence of multiple serotypes with the endemic signs appeared in some
      part of the areas. Chikungunya was a newly emerging disease in Guangdong since
      local people were lack of basic immunity barrier. Surveillance and control
      programs thus seemed important.

PMID- 24739558
TI  - [Application of Best Subsets Regression on the risk classification for
      Spermophilus Dauricus Focus].
AB  - OBJECTIVE: To study the risk classification of animal plague in Spermophilus
      Dauricus Focus, using the Best Subsets Regression (BSR) model. METHODS: Matlab,
      BSR and exponential smoothing were employed to develop and evaluate a model for
      risk classification as well as to forecast plague epidemics at the Spermophilus
      Dauricus Focus. Data was based upon the Inner Mongolia surveillance programs.
      This model involved 7 risk factors, including density of Spermophilus dauricus,
      percentage of hosts infested, host flea index, percentage of nests infested, nest
      flea index, percentage of runways infested, and runway flea index. RESULTS:
      Forecasting values of the classification model(CM)were calculated and grouped
      into 3 risk levels. Values that over 2/3 of the CM would indicate the existence
      of potential epidemics while those below 1/3 would indicate that there were no
      risk for epidemics but when values that were in between would indicate that there
      exist for high risk. Annually, during the observation period in the Inner
      Mongolia Spermophilus Dauricus Foci, the detection of Yersinia pestis gave a risk
      rating value of 1 which stood for existing epidemics, while nil detection rate
      generated a 'zero' value which representing the situation of non-epidemic. The
      overall plague epidemics forecasting surveillance programs in 2012 at the
      Spermophilus Dauricus Foci indicated that no active plague was observed. When the
      forecasting values became over 2/3, combinations of all the risk factors would
      achieve the consistency rates of 100%. When the forecasting values were below
      1/3, combinations of at least the first 4 factors could also achieve the
      consistency rates of 100%. However, when the forecasting values fell in between,
      combinations of at least the first 4 factors would achieve the consistency rates
      of around 50%. CONCLUSION: Results from our study showed that plague would not be
      active to become epidemic, in 2012.

PMID- 24739559
TI  - [Development of forecasting models for fatal road traffic injuries].
AB  - OBJECTIVE: To develop the forecasting models for fatal road traffic injuries and
      to provide evidence for predicting the future trends on road traffic injuries.
      METHODS: Data on the mortality of road traffic injury including factors as gender
      and age in different countries, were obtained from the World Health Organization
      Mortality Database. Other information on GDP per capita, urbanization,
      motorization and education were collected from online resources of World Bank,
      WHO, the United Nations Population Division and other agencies. We fitted
      logarithmic models of road traffic injury mortality by gender and age group,
      including predictors of GDP per capita, urbanization, motorization and education.
      Sex- and age-specific forecasting models developed by WHO that including GDP per
      capita, education and time etc. were also fitted. Coefficient of
      determination(R(2)) was used to compare the performance between our modes and WHO
      models. RESULTS: 2 626 sets of data were collected from 153 countries/regions for
      both genders, between 1965 and 2010. The forecasting models of road traffic
      injury mortality based on GDP per capita, motorization, urbanization and
      education appeared to be statistically significant(P < 0.001), and the
      coefficients of determination for males at the age groups of 0-4, 5-14, 15-24, 25
      34, 35-44, 45-54, 55-64, 65+ were 22.7% , 31.1%, 51.8%, 52.3%, 44.9%, 41.8%,
      40.1%, 25.5%, respectively while the coefficients for these age groups in women
      were 22.9%, 32.6%, 51.1%, 49.3%, 41.3%, 35.9%, 30.7%, 20.1%, respectively. The
      WHO models that were based on the GDP per capita, education and time variables
      were statistically significant (P < 0.001)and the coefficients of determination
      were 14.9% , 22.0%, 31.5%, 33.1% , 30.7%, 28.5%, 27.7% and 17.8% for males, but
      14.1%, 20.6%, 30.4%, 31.8%, 26.7%, 24.3%, 17.3% and 8.8% for females,
      respectively. CONCLUSION: The forecasting models that we developed seemed to be
      better than those developed by WHO.

PMID- 24739560
TI  - [Sources of infection on human plague in Qinghai province].
AB  - OBJECTIVE: To study the biological and genetic characteristics of 119 strains of
      Yersinia (Y.) pestis isolated from plague patients in Qinghai province, from 1958
      2012. METHODS: Both regular methods and different region(DFR)molecular typing
      techniques were used to study the epidemiological characteristics on 119 strains
      of Y. pesticin Qinghai during 1958-2012. Sources of Y. pestis from two outbreaks,
      in Nangqian county in 2004 and in Xinghai county in 2009,Qinghai province were
      also analyzed. RESULTS: 105 strains of Y. pestis were identified as Qinghai-Tibet
      Plateau Ecotype while the other 6 strains as Qilian Mountains Ecotype. 84.03%
      (100/119) of the tested strains carried 4 virulence factors F1(+), Pst I(+),
      VW(+) and Pgm(+)). 97.30% (72/74) of the tested strains showed high virulence.
      Strains that carrying 52*10(6), 65*10(6), 92*10(6) plasmids were distributed in
      Hainan, Haibei, Haixi,Yushu,Guoluo, Huangnan and Huangyuan counties. Genomovar 5
      and 8 were the main gene types that circling around Qinghai Lake. Genomovar 10
      was found in strains of Y. pesticin Nangqian county while Genomovar 8 was found
      in the strains isolated from human plague patient during the epidemics in Xinghai
      county in Qinghai. CONCLUSION: Data from biological and genetic analyses on the
      epidemics of human plague in Nangqian county in 2004 and in Xinghai county in
      2009 demonstrated that methods as DFR genotyping and virulence factors profiles,
      as well as plasmids profiles were powerful tools in confirming the human plague
      epidemics and sources of infection.

PMID- 24739561
TI  - [Genotyping and its epidemiological significance on Yunnan Yersinia pestis under
      Fse I enzyme digestion method].
AB  - OBJECTIVE: To create the fingerprint library of Yunnan Yersinia pestis by pulse
      field gel electrophoresis(PFGE)with Fse I enzyme digestion method and to study
      its epidemiological significance. METHODS: We used rare cutting restriction
      enzyme Fse? to digest Yunnan Yersinia pestis strains that were isolated from foci
      including Rattus flavipectus Plague Focus,Apodemus chevrieri-Eothenomys miletus
      Plague Focus and Yulong Plague Focus. Fingerprints to Bionumerics software were
      used for cluster analysis. RESULTS: 30 tested strains were divided into 16
      genotypes with the similarity value as 79.8%-100.0% . 16 genotypes wee formed
      into 4 clusters, with one consisted of only EV76 while the other three belonged
      to Rattus flavipectus,Apodemus chevrieri- Eothenomys miletus and Yulong clusters,
      respectively. CONCLUSIONS: PFGE genotypes of Yunnan Yersinia pestis accorded with
      its ecotypes and biovars, with clustered regional features. The strains isolated
      from Yulong showed an unique PFGE type, indicating a new clone group was
      identified.

PMID- 24739562
TI  - [Detection of measles virus genome by reverse transcription-loop mediated
      isothermal amplification(RT-LAMP)].
AB  - OBJECTIVE: To establish a tool regarding the reverse transcription-loop mediated
      isothermal amplification(RT-LAMP)assay for the detection of measles virus.
      METHODS: Measles virus RNA was extracted by Trizol-LS reagent. The 1 242-1 442
      sequence contained 8 primer sites of 6 sets primer. The RT-LAMP gene
      amplification was detected by a real-time PCR facility with AMV reverse
      transcriptase at 63  degrees C for 60 min before terminating the amplification at
      80  degrees C 2 min. The amplified product was monitored by agarose gel
      electrophoresis and loop amp fluorescence methods. Sensitivity and specificity of
      the RT-LAMP assay were subsequently compared with that of conventional RT-PCR.
      RESULTS: The whole procedure of RT-LAMP took about 1 hour. The amplified products
      appeared to be a ladder-like electrophoresis pattern during the process of
      agarose gel electrophoresis. The appearance of color change in the reactions with
      positive controls and positive samples was evident at 20 min after RT-LAMP
      initiation. The sensitivity of RT-LAMP assay was 100-fold higher than that of the
      conventional RT-PCR of the real-time RT-PCR. The specificity of MV-specific LAMP
      assay was conformed by negative amplification of dengue virus and Japanese
      encephalitis virus. CONCLUSION: RT-LAMP assay appeared rapid, cost-effective,
      highly sensitive and specific for the detection of genes of interest and proved
      to be potentially useful for surveillance on MV, especially in the grass root
      laboratories or for field studies.

PMID- 24739563
TI  - [Study on the association between catechol-O-methyltransferase gene polymorphisms
      and type 2 diabetes mellitus].
AB  - OBJECTIVE: To evaluate the association between the two single nucleotide
      polymorphisms located in catechol-O-methyltransferase (COMT) gene and type 2
      diabetes mellitus (T2DM)in Han population in Guangdong province. METHODS: Two
      tagSNPs (rs4646312 and rs4680) were picked out from COMT gene. Using the
      SNPscan(TM) Kit, SNP genotyping was then performed, in two cohorts, including 595
      cases and 725 controls. Finally, Chi-square test, logistic regression model and
      other methods were employed for statistical analysis. RESULTS: The frequencies of
      TT, CT and CC of rs4646312 appeared to be 304(51.1%), 234(39.3%)and 57 (8.6%) in
      cases, 323 (44.6%), 319 (44.0%) and 83(11.4%)in controls, respectively. The
      frequencies of GG,GA and AA of rs4680 were 311(52.4%), 236 (39.8%) and 46(7.8%)in
      cases, 417(57.7%), 265 (36.6%) and 41 (5.7%) in controls, respectively. RESULTS:
      showed that SNP rs4646312 was significantly associated with T2DM both in allelic
      association analysis (P = 0.020,OR = 1.26, 95%CI:1.04-1.53)and in recessive model
      (P = 0.022, OR = 1.35, 95% CI:1.05-1.74)after adjustment for sex,BMI and TG. The
      association between rs4680 and T2DM was not significant, but BMI was remarkably
      different among the three genotypes of rs4680 after controlling for other
      factors. CONCLUSION: SNP rs4646312 of COMT gene was associated with the increased
      risk of T2DM in Han population in Guangdong province. However, rs4680 was not
      significantly associated with T2DM.

PMID- 24739564
TI  - [Association between adiponectin rs2241766, rs1501299 polymorphisms and the risk
      of colorectal cancer].
AB  - OBJECTIVE: To explore the association between adiponectin rs2241766, rs1501299
      polymorphisms and gene-environment interaction and the risk of colorectal
      cancer(CRC). METHODS: Four hundred CRC patients confirmed by histopathology and
      400 healthy controls were recruited in this study. Cases and controls were
      matched on age and gender. A well-designed questionnaire was used to collect the
      information of demography, lifestyle and dietary habit on the 400 case-control
      pairs. Polymerase chain reaction-restriction fragment length polymorphism(PCR
      RFLP)was applied to detect the adiponectin rs2241766 and rs1501299 genotypes.
      RESULTS: Data from conditional logistic regression analysis showed that those
      carrying TG+GG genotype on rs2241766 having an increased risk compared to those
      that carrying TT genotype(OR = 1.354, 95%CI:1.004-1.827), and those that carrying
      GT+TT genotype on rs1501299 having an decreased risk when compared to those that
      carrying GG genotype(OR = 0.680, 95% CI:0.501-0.923), after adjusted by factors
      as CRC family history,BMI, sedentary time, red meat consumption, and tea-drinking
      habit. Data from generalized multifactor dimensionality reduction showed that the
      gene-environment interaction among rs2241766, rs1501299 and red meat consumption
      on the risk of CRC might be significant(P = 0.001). A significant dosage effect
      with an increasing number of risk genotypes was observed as the risk of CRC
      increased (chi(2) = 8.458, P = 0.004). CONCLUSION: Both adiponectin rs2241766 and
      rs1501299 were associated with CRC risk and the two SNPs might have worked
      together with red meat consumption in affecting the CRC risk.

PMID- 24739565
TI  - [Association between the single nucleotide polymorphisms of human CD36 gene and
      acute coronary syndrome].
AB  - OBJECTIVE: The aim of the present study was to assess the association between the
      polymorphisms of CD36 gene and acute coronary syndrome(ACS). METHODS: Genotypes
      of CD36 single nucleotide polymorphisms were detected under PCR-RFLP in 522
      patients with ACS and 1 215 controls. RESULTS: For people under Han and Uygur
      ethnicities, the distribution of genotypes and allele of rs1722505 was
      significantly different between ACS and the controls(all P < 0.05). For Han
      population, the frequency of A allele of rs17154181 was significantly lower in
      ACS group than that in the control group(P = 0.034). Results from logistic
      regression analysis showed that the AA+AG genotype of rs1722505 was significantly
      higher in ACS patients than that in controls both between the Hans and the
      Uygurs(OR = 1.436, 95%CI:1.047-1.970, P = 0.025;OR = 1.589, 95%CI:1.009-2.473, P
      = 0.046, respectively). For Han people,AA+AG genotype of rs17154181 was
      significantly lower in ACS patients than that in controls(OR = 0.667, 95%
      CI:0.494-0.900, P = 0.008). CONCLUSION: Data from the present study suggested
      that the CD36 gene might serve as a genetic marker of ACS in both Han and Uygur
      populations.

PMID- 24739566
TI  - [Characteristics of brachial-ankle pulse wave velocity and its relationship with
      risk factors of cardiovascular diseases in populations having health check-up
      programs].
AB  - OBJECTIVE: To investigate the characteristics of brachial-ankle pulse wave
      velocity (baPWV)in populations having health check-up and to explore its
      relationship with risk factors of cardiovascular diseases. METHODS: 13 841 people
      who had health check-up were included and their baPWV were tested by automatic
      arteriosclerosis measurement system. All people were inquired about their
      diseases history, while height, weight, body mass index(BMI), blood pressure,
      fasting blood-glucose as well as serum lipid were also measured. RESULTS: With
      increasing of age, baPWV were increased both in males and females. The baPWV of
      male aged less than 60 years was significantly higher than that of female less
      than 60. Multi-variable regressive analysis showed the age, systolic
      pressure,BMI, fasting blood-glucose, uric acid and triglyceride were the risk
      factors of baPWV. CONCLUSION: BaPWV values of health check-up population in
      Chengdu area demonstrated different characteristics in different age and gender
      group. Attention should be paid on baPWV measurement among elder people,
      especially the elder women, in order to prevent cardiovascular events happening
      in high risk population.

PMID- 24739567
TI  - [How to write high-quality epidemiological research paper V. Guidelines for
      Transparent Reporting of Outbreak Reports and Intervention Studies of Nosocomial
      Infection (ORION statement)].

PMID- 24739568
TI  - [Progress on study of co-infection with HIV and schistosome].

PMID- 24739569
TI  - [A review on the effectiveness and its influencing factors of measles vaccine].

PMID- 24739570
TI  - LPHN3, a presynaptic adhesion-GPCR implicated in ADHD, regulates the strength of
      neocortical layer 2/3 synaptic input to layer 5.
AB  - BACKGROUND: Latrophilins (LPHNs) are a small family of neuronal adhesion-GPCRs
      originally discovered as receptors for the black widow spider toxin alpha
      latrotoxin. Mutations in LPHN3 have recently been identified as risk factors for
      attention deficit hyperactivity disorder (ADHD) in humans, but their
      physiological function has remained elusive. In this study, we tested two
      hypotheses regarding LPHN3 function: (1) LPHN3 regulates synaptic transmission by
      modulating probability of release; and (2) LPHN3 controls synapse development and
      the abundance of synapses. RESULTS: We manipulated LPHN3 expression in mouse
      layer 2/3 (L2/3) pyramidal neurons and examined the consequences on the L2/3 to
      L5 cortical microcircuit. Employing an optogenetic strategy combined with shRNA
      knockdown of LPHN3, we found that LPHN3 did not influence probability of release
      at synapses formed by L2/3 neurons onto L5 pyramidal cells. The strength of L2/3
      afferent input to L5, however, was weakened by loss of LPHN3. Using Synaptophysin
      GFP as an anatomical marker of presynaptic terminals, we found that the density
      of synapses formed by L2/3 axons in L5 was reduced when LPHN3 was lost. Finally,
      we investigated the structural organization of the extracellular domain of LPHN3.
      We used single particle negative stain electron microscopy to image the
      extracellular domain of LPHN3 and showed that the Olfactomedin and Lectin domains
      form a globular domain on an elongated stalk. Cell-based binding experiments with
      mutant proteins revealed that the Olfactomedin domain was required for binding to
      FLRT3, whereas both the Olfactomedin and Lectin domains were involved in binding
      to Teneurin 1. Mutant LPHN3 lacking the Olfactomedin domain was not capable of
      rescuing the deficit in presynaptic density following knockdown of endogenous
      LPHN3. CONCLUSIONS: We find that LPHN3 regulates the number of synapses formed by
      L2/3 neurons in L5 and the strength of synaptic drive from the L2/3-L5 pathway.
      The Olfactomedin domain of LPHN3 is required for this effect on synapse number
      and binding to its postsynaptic ligand FLRT3. We propose that LPHN3 functions in
      synaptic development and is important in determining the connectivity rates
      between principal neurons in the cortex.

PMID- 24739571
TI  - Non-coding RNAs as direct and indirect modulators of epigenetic regulation.
AB  - Epigenetic regulation of gene expression is an increasingly well-understood
      concept that explains much of the contribution of an organism's environment and
      experience to its biology. However, discussion persists as to which mechanisms
      can be classified as epigenetic. Ongoing research continues to uncover novel
      pathways, including the important role of non-protein coding RNA transcripts in
      epigenetic gene regulation. We know that the majority of human and other
      mammalian transcripts are not translated but that many of these are nonetheless
      functional. These non-coding RNAs (ncRNAs) can be short (<200 nt) or long (<200
      nt) and are further classified by genomic origin and mechanism of action. We
      discuss examples of ncRNAs that interact with histone modifying complexes or DNA
      methyltransferases to regulate gene expression, others that are targets of these
      epigenetic mechanisms, and propose a model in which such transcripts feed back
      into an epigenetic regulatory network. 

PMID- 24739572
TI  - Effects of enamel matrix derivative on the proliferation and osteogenic
      differentiation of human gingival mesenchymal stem cells.
AB  - INTRODUCTION: Gingiva-derived mesenchymal stem cells (GMSCs) have recently been
      harvested and applied for rebuilding lost periodontal tissue. Enamel matrix
      derivative (EMD) has been used for periodontal regeneration and the formation of
      new cementum with inserting collagen fibers; however, alveolar bone formation is
      minimal. Recently, EMD has been shown to enhance the proliferation and
      mineralization of human bone marrow mesenchymal stem cells. Because the gingival
      flap is the major component to cover the surgical wound, the effects of EMD on
      the proliferation and mineralization of GMSCs were evaluated in the present
      study. METHODS: After single cell suspension, the GMSCs were isolated from the
      connective tissues of human gingiva. The colony forming unit assay of the
      isolated GMSCs was measured. The expression of stem cell markers was examined by
      flow cytometry. The cellular telomerase activity was identified by polymerase
      chain reaction (PCR). The osteogenic, adipogenic and neural differentiations of
      the GMSCs were further examined. The cell proliferation was determined by MTS
      assay, while the expression of mRNA and protein for mineralization (including
      core binding factor alpha, cbfalpha-1; alkaline phosphatase, ALP; and
      osteocalcin, OC; ameloblastin, AMBN) were analyzed by real time-PCR, enzyme
      activity and confocal laser scanning microscopy. RESULTS: The cell colonies could
      be easily identified and the colony forming rates and the telomerase activities
      increased after passaging. The GMSCs expressed high levels of surface markers for
      CD73, CD90, and CD105, but showed low expression of STRO-1. Osteogenic,
      adipogenic and neural differentiations were successfully induced. The
      proliferation of GMSCs was increased after EMD treatment. ALP mRNA was
      significantly augmented by treating with EMD for 3 hours, whereas AMBN mRNA was
      significantly increased at 6 hours after EMD treatment. The gene expression of OC
      was enhanced at the dose of 100 MUg/ml EMD at day 3. Increased protein expression
      for cbfalpha-1 at day 3, for ALP at day 5 and 7, and for OC at week 4 after the
      EMD treatments were observed. CONCLUSIONS: Human GMSCs could be successfully
      isolated and identified. EMD treatments not only induced the proliferation of
      GMSCs but also enhanced their osteogenic differentiation after induction.

PMID- 24739574
TI  - DNA damage: De-sanitizing tumour cells.

PMID- 24739573
TI  - Unravelling mechanisms of p53-mediated tumour suppression.
AB  - p53 is a crucial tumour suppressor that responds to diverse stress signals by
      orchestrating specific cellular responses, including transient cell cycle arrest,
      cellular senescence and apoptosis, which are all processes associated with tumour
      suppression. However, recent studies have challenged the relative importance of
      these canonical cellular responses for p53-mediated tumour suppression and have
      highlighted roles for p53 in modulating other cellular processes, including
      metabolism, stem cell maintenance, invasion and metastasis, as well as
      communication within the tumour microenvironment. In this Opinion article, we
      discuss the roles of classical p53 functions, as well as emerging p53-regulated
      processes, in tumour suppression.

PMID- 24739580
TI  - Tumour heterogeneity: A cooperative tumour cell community.

PMID- 24739585
TI  - Tumour suppressors: Master weaver regulates guardian.

PMID- 24739582
TI  - Turning ecology and evolution against cancer.
AB  - The fight against cancer has drawn researchers from a wide variety of
      disciplines, ranging from molecular biology to physics, but the perspective of an
      ecological theorist has been mostly overlooked. By thinking about the cells that
      make up a tumour as an endangered species, cancer vulnerabilities become more
      apparent. Studies in conservation biology and microbial experiments indicate that
      extinction is a complex phenomenon, which is often driven by the interaction of
      ecological and evolutionary processes. Recent advances in cancer research have
      shown that tumours, like species striving for survival, harbour intricate
      population dynamics, which suggests the possibility to exploit the ecology of
      tumours for treatment.

PMID- 24739586
TI  - In response.

PMID- 24739578
TI  - Developments in preclinical cancer imaging: innovating the discovery of
      therapeutics.
AB  - Integrating biological imaging into early stages of the drug discovery process
      can provide invaluable readouts of drug activity within complex disease settings,
      such as cancer. Iterating this approach from initial lead compound identification
      in vitro to proof-of-principle in vivo analysis represents a key challenge in the
      drug discovery field. By embracing more complex and informative models in drug
      discovery, imaging can improve the fidelity and statistical robustness of
      preclinical cancer studies. In this Review, we highlight how combining advanced
      imaging with three-dimensional systems and intravital mouse models can provide
      more informative and disease-relevant platforms for cancer drug discovery. 

PMID- 24739589
TI  - The effects of citicoline on acute ischemic stroke: a review.
AB  - Early reopening of the occluded artery is, thus, important in ischemic stroke,
      and it has been calculated that 2 million neurons die every minute in an ischemic
      stroke if no effective therapy is given; therefore, "Time is Brain." In massive
      hemispheric infarction and edema, surgical decompression lowers the risk of death
      or severe disability defined as a modified Rankin Scale score greater than 4 in
      selected patients. The majority, around 80%-85% of all ischemic stroke victims,
      does not fulfill the criteria for revascularization therapy, and also for these
      patients, there is no effective acute therapy. Also there is no established
      effective acute treatment of spontaneous intracerebral bleeding. Therefore, an
      effective therapy applicable to all stroke victims is needed. The neuroprotective
      drug citicoline has been extensively studied in clinical trials with volunteers
      and more than 11,000 patients with various neurologic disorders, including acute
      ischemic stroke (AIS). The conclusion is that citicoline is safe to use and may
      have a beneficial effect in AIS patients and most beneficial in less severe
      stroke in older patients not treated with recombinant tissue plasminogen
      activator. No other neuroprotective agent had any beneficial effect in
      confirmative clinical trials or had any positive effect in the subgroup analysis.
      Citicoline is the only drug that in a number of different clinical stroke trials
      continuously had some neuroprotective benefit. 

PMID- 24739588
TI  - Multidimensional associative factors for improvement in pain, function, and
      working capacity after rehabilitation of whiplash associated disorder: a
      prognostic, prospective outcome study.
AB  - BACKGROUND: Whiplash associated disorders (WAD) have dramatic consequences for
      individual and public health. Risk factors for better and worse outcomes are
      important to optimize management. This study aimed to determine short- and mid
      term associative co-factors of neck pain relief, improved physical functioning,
      and improved working capacity (dependent variables) in patients suffering from
      whiplash associated disorder who participated in a standardized, inpatient pain
      management program. METHODS: Naturalistic, observational, prospective cohort
      study. Outcome was measured by standardized assessment instruments. Co-factors
      covered sociodemographics, comorbidities, social participation, affective health,
      and coping abilities. Stepwise, multivariate linear regression analysis was
      performed at discharge and at the 6-month follow-up. RESULTS: All regression
      models explained high proportions of variance (53.3% - 72.1%). The corresponding
      baseline level was significantly associated with a change in every dependent
      variable (explained variances: 11.4%-56.7%). Pain relief significantly depended
      on improved function and vice-versa (3.4%-14.8%). Improved ability to decrease
      pain was associated with pain relief at discharge (9.6%). Functional improvement
      was associated with decreased catastrophizing (19.4%) at discharge and decreased
      depression (20.5%) at the 6 month follow-up. CONCLUSIONS: Pain relief, improved
      physical function and working capacity were associated with each other. Improved
      coping (catastrophizing and ability to decrease pain) and reduced depression may
      act as important predictors for pain relief and improved function. These findings
      offer toe-holds for optimized therapy of chronic WAD.

PMID- 24739590
TI  - Rosuvastatin improves plaque morphology in cerebral embolism patients with normal
      low-density lipoprotein and severe aortic arch plaque.
AB  - The effect of rosuvastatin was investigated on complicated aortic arch plaque
      (CAP) morphology and lipid profiles in acute cerebral embolism (CE) patients with
      normal low-density lipoprotein-cholesterol (LDL-c) levels. Transesophageal
      echocardiography (TEE) studies were performed in 56 consecutive CE patients with
      LDL-c less than 140 mg/dL who were not taking lipid-lowering agents at baseline.
      CAP observed by TEE was defined as the presence of greater than 4-mm diameter,
      ulcerated, or mobile aortic plaque. Patients were divided into those with CAP
      versus without CAP (group A, n=24, age 69+/-8 years) and without CAP (group B,
      n=32, age 62+/-10 years). Of the 24 group A patients, 18 received 5 mg/d of
      rosuvastatin for 6 months and had follow-up TEE studies. In Group A, the baseline
      values of high-density lipoprotein-cholesterol (HDL-c) and apolipoprotein A-1
      (ApoA-1) were significantly lower than in Group B (44+/-15 versus 55+/-15 mg/dL,
      P=.0059; 103+/-19 versus 137+/-25 mg/dL, P=.0006, respectively) and age and serum
      high-sensitivity C-reactive protein concentration were significantly higher (69+/
      8 vs. 62+/-10 years, P=.0080; 2.34+/-3.05 vs. 0.67+/-1.00 mg/dL, P=.0054,
      respectively). By multivariate logistic regression analysis, ApoA-1 was shown to
      be an independent predictor of CAP (odds ratio=.894, 95% confidence intervals
      .800-.996, P=.0483). In the 18 group A patients receiving rosuvastatin for 6
      months, aortic arch plaque diameter and serum LDL-c were significantly decreased
      (5.8+/-2.2 to 5.1+/-2.1 mm, P=.0377; 110+/-23 to 81+/-23 mg/dL, P=.0008,
      respectively), whereas serum HDL-c and ApoA-1 concentrations were significantly
      increased (42+/-8 to 52+/-9 mg/dL, P=.0002; 109+/-22 to 135+/-15 mg/dL, P=.0002,
      respectively). Plaques were morphologically improved in 11 patients, unchanged in
      6, and worsened in 1. These data suggest that rosuvastatin improves plaque
      morphology concomitant with improving lipid profiles in CE patients with normal
      LDL-c levels.

PMID- 24739591
TI  - The infarct location predicts the outcome of single small subcortical infarction
      in the territory of the middle cerebral artery.
AB  - BACKGROUND: Single small subcortical infarction (SSSI) in the territory of the
      middle cerebral artery (MCA) may be classified as proximal SSSI (pSSSI) or distal
      SSSI (dSSSI) according to its extension to the MCA. We sought to investigate the
      outcome of different types of SSSIs. METHODS: We assessed 177 patients who had an
      SSSI (67 pSSSI and 110 dSSSI) in the perforator territory of MCA. The clinical
      characteristics, neurologic status (initial National Institutes of Health Stroke
      Scale score at admission and modified Rankin Scale [mRS] score at 1 year), and
      clinical treatments at 1 year were evaluated. RESULTS: Among the 177 patients,
      130 had favorable (mRS score<=1) and 41 had unfavorable outcome (mRS score>=2) at
      1 year, dSSSI had higher mRS than pSSSI at 1 year (1 [0-2] versus 0 [0-1];
      P=.013). The age (odds ratio [OR] 1.049, 95% confidence interval [CI] 1.002
      1.098; P=.041) and distal location of the lesion (OR 2.687, 95% CI 1.039-6.948;
      P=.042) were found to be independent risk factors of 1-year unfavorable outcome
      of SSSIs. CONCLUSIONS: SSSI has a heterogeneous outcome at 1 year according to
      the lesion location.

PMID- 24739592
TI  - Differential lesion patterns on T2-weighted magnetic resonance imaging and fluid
      attenuated inversion recovery sequences in cryptogenic stroke patients with
      patent foramen ovale.
AB  - BACKGROUND: The present study aimed to determine lesion patterns and the stroke
      mechanisms in cryptogenic ischemic stroke patients with patent foramen ovale
      (PFO) on T2-weighted magnetic resonance imaging (T2WI) and fluid-attenuated
      inversion recovery (FLAIR) sequences combined. METHODS: In this retrospective
      study, 38 patients with cryptogenic stroke and an isolated PFO compared with 51
      cryptogenic stroke patients without PFO were evaluated and their characteristics
      of lesion patterns on T2WI and FLAIR sequences combined were investigated. The
      number, distribution of small ischemic lesions, and the frequency of multiple
      small ischemic lesions were analyzed between the 2 groups. RESULTS: Thirty-two of
      38 patients had a total of 341 small ischemic lesions in cryptogenic stroke
      patients with PFO versus 24 of 51 patients with 156 small ischemic lesions in
      patients without PFO, and, 8.97+/-7.91 and 3.19+/-4.82 ischemic lesions per
      person, respectively. Multiple small ischemic lesions occurred more frequently in
      cryptogenic stroke patients with PFO (25 of 38 patients, 66%) than in patients
      without PFO (16 of 51 patients, 31%; P=.001). Subcortical frontal and parietal
      small lesions were more frequent in cryptogenic stroke patients with PFO (28 of
      38 patients, 74%) than in patients without PFO (18 of 51 patients, 35%; P<.0001).
      CONCLUSIONS: Multiple small ischemic lesions and subcortical frontal and parietal
      small lesions were significantly associated with cryptogenic stroke patients with
      PFO, suggesting that paradoxical embolism may be the mechanism of PFO-associated
      cryptogenic stroke patients.

PMID- 24739593
TI  - A comparative study of dual versus monoantiplatelet therapy in patients with
      acute large-artery atherosclerosis stroke.
AB  - BACKGROUND: Antiplatelet drugs are recommended for patients with acute
      noncardioembolic stroke. However, few randomized clinical trials have
      investigated the safety and efficacy of dual antiplatelet therapy for these
      patients. The aim of this study was to evaluate the effects of treatment with
      clopidogrel and aspirin (combination therapy) and aspirin alone (monotherapy) on
      neurologic deterioration, platelet activation, and other short-term outcomes in
      patients with acute large-artery atherosclerosis stroke. MATERIALS AND METHODS:
      Altogether 574 patients with acute (<=2 days) large-artery atherosclerosis stroke
      were randomly assigned to receive either combined clopidogrel and aspirin or
      aspirin alone. Platelet aggregation and platelet-leukocyte aggregation studies
      were performed at days 1 and 30. Primary outcomes including recurrent ischemic
      stroke, neurologic deterioration, periphery vascular events, and myocardial
      infarction were monitored. Safety endpoints were hemorrhagic episodes and death.
      RESULTS: The prevalence of neurologic deterioration and recurrent ischemic stroke
      were lower in patients in the combination therapy group than in those of the
      monotherapy group (3.52% versus 9.78% and 1.76% versus 6.29%, respectively). At
      day 30 of treatment, the platelet aggregations and platelet-leukocyte aggregates
      were lower in patients who were treated with clopidogrel and aspirin than in
      patients given aspirin alone (P < .001). CONCLUSIONS: For patients with acute
      large-artery atherosclerosis stroke, treatment with clopidogrel and aspirin for 1
      month provided significantly greater inhibition of platelet activity than aspirin
      alone. Thus, dual therapy can be safer and more effective in reducing ischemic
      stroke recurrence and neurologic deterioration.

PMID- 24739594
TI  - Suicide or undetermined intent? A register-based study of signs of
      misclassification.
AB  - BACKGROUND: Several studies have concluded that some deaths classified as
      undetermined intent are in fact suicides, and it is common in suicide research in
      Europe to include these deaths. Our aim was to investigate if information on
      background variables would be helpful in assessing if deaths classified as
      undetermined intent should be included in the analyses of suicides. METHODS: We
      performed a register study of 31,883 deaths classified as suicides and 9,196
      deaths classified as undetermined intent in Sweden from 1987 to 2011. We compared
      suicide deaths with deaths classified as undetermined intent with regard to
      different background variables such as sex, age, country of birth, marital
      status, prior inpatient care for self-inflicted harm, alcohol and drug abuse,
      psychiatric inpatient care, and use of psychotropics. We also performed a
      multivariate analysis with logistic regression. RESULTS: Our results showed
      differences in most studied background factors. Higher education was more common
      in suicides; hospitalization for self-inflicted harm was more common among female
      suicides as was prior psychiatric inpatient care. Deaths in foreign-born men were
      classified as undetermined intent in a higher degree and hospitalization for
      substance abuse was more common in undetermined intents of both sexes. Roughly
      50% of both suicide and deaths classified as undetermined intent had a filled
      prescription of psychotropics during their last six months. Our multivariate
      analysis showed male deaths to more likely be classified as suicide than female:
      OR: 1.13 (1.07-1.18). The probability of a death being classified as suicide was
      also increased for individuals aged 15-24, being born in Sweden, individuals who
      were married, and for deaths after 1987-1992. CONCLUSION: By analyzing Sweden's
      unique high-validity population-based register data, we found several differences
      in background variables between deaths classified as suicide and deaths
      classified as undetermined intent. However, we were not able to clearly
      distinguish these two death manners. For future research we suggest, separate
      analyses of the two different manners of death.

PMID- 24739595
TI  - Unmet needs of patients with chronic obstructive pulmonary disease (COPD): a
      qualitative study on patients and doctors.
AB  - BACKGROUND: Chronic Obstructive Pulmonary Disease (COPD) is a chronic disease
      with repeated exacerbations resulting in gradual debilitation. The quality of
      life has been shown to be poor in patients with COPD despite efforts to improve
      self-management. However, the evidence on the benefit of self-management in COPD
      is conflicting. Whether this could be due to other unmet needs of patients have
      not been investigated. Therefore, we aimed to explore unmet needs of patients
      from both patients and doctors managing COPD. METHODS: We conducted a qualitative
      study with doctors and patients in Malaysia. We used convenience sampling to
      recruit patients until data saturation. Eighteen patients and eighteen doctors
      consented and were interviewed using a semi-structured interview guide. The
      interviews were audio-recorded, transcribed verbatim and checked by the
      interviewers. Data were analysed using a thematic approach. RESULTS: The themes
      were similar for both the patients and doctors. Three main themes emerged:
      knowledge and awareness of COPD, psychosocial and physical impact of COPD and the
      utility of self-management. Knowledge about COPD was generally poor. Patients
      were not familiar with the term chronic obstructive pulmonary disease or COPD.
      The word 'asthma' was used synonymously with COPD by both patients and doctors.
      Most patients experienced difficulties in their psychosocial and physical
      functions such as breathlessness, fear and helplessness. Most patients were not
      confident in self-managing their illness and prefer a more passive role with
      doctors directing their care. CONCLUSIONS: In conclusion, our study showed that
      knowledge of COPD is generally poor. There was mislabelling of COPD as asthma by
      both patients and physicians. This could have resulted in the lack of
      understanding of treatment options, outcomes, and prognosis of COPD. The
      misconception that cough due to COPD was contagious, and breathlessness that
      resulted from COPD, had important physical and psychosocial impact, and could
      lead to social isolation. Most patients and physicians did not favour self
      management approaches, suggesting innovations based on self-management may be of
      limited benefit.

PMID- 24739596
TI  - Exploitation of semantic methods to cluster pharmacovigilance terms.
AB  - Pharmacovigilance is the activity related to the collection, analysis and
      prevention of adverse drug reactions (ADRs) induced by drugs. This activity is
      usually performed within dedicated databases (national, European,
      international...), in which the ADRs declared for patients are usually coded with
      a specific controlled terminology MedDRA (Medical Dictionary for Drug Regulatory
      Activities). Traditionally, the detection of adverse drug reactions is performed
      with data mining algorithms, while more recently the groupings of close ADR terms
      are also being exploited. The Standardized MedDRA Queries (SMQs) have become a
      standard in pharmacovigilance. They are created manually by international boards
      of experts with the objective to group together the MedDRA terms related to a
      given safety topic. Within the MedDRA version 13, 84 SMQs exist, although several
      important safety topics are not yet covered. The objective of our work is to
      propose an automatic method for assisting the creation of SMQs using the
      clustering of semantically close MedDRA terms. The experimented method relies on
      semantic approaches: semantic distance and similarity algorithms, terminology
      structuring methods and term clustering. The obtained results indicate that the
      proposed unsupervised methods appear to be complementary for this task, they can
      generate subsets of the existing SMQs and make this process systematic and less
      time consuming. 

PMID- 24739597
TI  - Ophthalmoplegia starting with a headache circumscribed in a line-shaped area: a
      subtype of ophthalmoplegic migraine?
AB  - Recurrent painful ophthalmoplegic neuropathy (RPON), formerly named
      ophthalmoplegic migraine (OM), is a rare condition characterized by the
      association of unilateral headaches and the ipsilateral oculomotor nerve palsy.
      The third cranial nerve is most commonly involved in the recurrent attacks. But
      it is still debated whether a migraine or an oculomotor neuropathy may be the
      primary cause of this disorder. Here, we report an elder patient who had a
      recurrent ophthalmoplegia starting with an unilateral headache circumscribed in
      an area shaped in a line linking the posterior-parietal region and the
      ipsilateral eye. And the headache had couple of features similar to that of
      migraine, such as past history of recurrent migraine attacks, accompaniments of
      nausea, vomiting, and phonophobia, response to flunarizine and sodium valproate.
      We may herein report a subtype of OM but not a RPON. This case report indicates
      that OM may exist as an entity and some OM may be wrongly grouped under the
      category of RPON in the current international headache classification. 

PMID- 24739598
TI  - Ultrasmooth metallic foils for growth of high quality graphene by chemical vapor
      deposition.
AB  - Synthesis of graphene by chemical vapor deposition is a promising route for
      manufacturing large-scale high-quality graphene for electronic applications. The
      quality of the employed substrates plays a crucial role, since the surface
      roughness and defects alter the graphene growth and cause difficulties in the
      subsequent graphene transfer. Here, we report on ultrasmooth high-purity copper
      foils prepared by sputter deposition of Cu thin film on a SiO2/Si template, and
      the subsequent peeling off of the metallic layer from the template. The surface
      displays a low level of oxidation and contamination, and the roughness of the
      foil surface is generally defined by the template, and was below 0.6 nm even on a
      large scale. The roughness and grain size increase occurred during both the
      annealing of the foils, and catalytic growth of graphene from methane (~1000 
      degrees C), but on the large scale still remained far below the roughness typical
      for commercial foils. The micro-Raman spectroscopy and transport measurements
      proved the high quality of graphene grown on such foils, and the room temperature
      mobility of the graphene grown on the template stripped foil was three times
      higher compared to that of one grown on the commercial copper foil. The presented
      high-quality copper foils are expected to provide large-area substrates for the
      production of graphene suitable for electronic applications. 

PMID- 24739599
TI  - Use of thromboelastography to tailor dual-antiplatelet therapy in patients
      undergoing treatment of intracranial aneurysms with the Pipeline embolization
      device.
AB  - BACKGROUND: Platelet function testing is controversial and not well studied in
      patients with neurovascular disease. OBJECTIVE: To evaluate the performance of
      thromboelastography (TEG) as a platelet function test in neurovascular patients
      treated with the Pipeline embolization device (PED). METHODS: A prospective
      protocol was instituted for platelet function testing in patients undergoing
      repair of intracranial aneurysms with the PED. All patients received dual
      antiplatelet therapy (DAT) and their response to both P2Y12 inhibitors and
      aspirin was quantified with TEG. Each patient's DAT induction strategy was
      tailored based on the percentage ADP-induced and percentage arachidonic acid
      induced platelet inhibition reported by TEG. Data collected included clinical
      presentation, aneurysm characteristics, treatment details, and periprocedural
      events. Patients were followed up clinically and/or angiographically at 30 days,
      6 months, and 1 year. RESULTS: Thirty-four PED procedures were performed on 31
      patients. TEG results altered the DAT strategy in 35% of patients. Technical
      success with the Pipeline placement was 100%. Two patients had minor strokes and
      five had transient ischemic attacks (TIAs). There have been no hemorrhagic
      complications. No patient had permanent neurologic deficits. Six of eight (75%)
      of patients with thromboembolic/TIA events were ADP-induced hyporesponders by
      TEG. Our 6- and 12-month angiographic occlusion rates were 78.9% and 89.5%,
      respectively. The 19 major branches covered by the PED that were assessed by
      follow-up imaging have all remained patent. CONCLUSIONS: Platelet function
      testing with TEG altered our DAT induction strategy in a significant number of
      cases. No hemorrhagic or disabling thromboembolic complications were seen in this
      series. Future studies should compare methods of platelet function testing and,
      possibly, no platelet function testing in neurovascular patients undergoing flow
      diversion and/or stent-assisted treatment of intracranial aneurysms.

PMID- 24739600
TI  - Matters of controversy regarding lipid therapy for Japanese patients with
      coronary artery disease.

PMID- 24739601
TI  - Contributors to newly developed coronary artery disease in patients with a
      previous history of percutaneous coronary intervention beyond the early phase of
      restenosis.
AB  - OBJECTIVE: The low-density lipoprotein cholesterol (LDL-C)/high-density
      lipoprotein cholesterol (HDL-C) ratio is considered to be a sensitive marker of
      the risk of atherosclerotic cardiovascular disease; however, in patients with a
      previous history of percutaneous coronary intervention (PCI), there is little
      information regarding the predictive value of this parameter beyond the period of
      early restenosis. The aim of this study was to investigate contributing factors
      to newly developed coronary artery disease in patients with a previous history of
      PCI after stabilization. METHODS: The clinical characteristics of 238 patients
      with a previous history of PCI who underwent coronary angiography following
      recurrent cardiac ischemia beyond the period of early restenosis were examined.
      RESULTS: Overall, 64% of the patients underwent late revascularization, while 31%
      and 50% underwent late target lesion revascularization and new lesion
      revascularization, respectively. A multivariate analysis identified the LDL-C/HDL
      C ratio to be an independent contributor to late revascularization (hazard ratio
      (HR), 1.37; p<0.001). Similarly, the independent contributors to late target
      lesion revascularization and new lesion revascularization were the non-HDL-C
      level and LDL-C/HDL-C ratio, respectively. Based on the median value of the LDL
      C/HDL-C ratio, the patients were classified into high and low LDL-C/HDL-C ratio
      groups. The log-rank test revealed a significantly higher incidence of late
      revascularization in the high-LDL-C/HDL-C ratio group than in the low-LDL-C/HDL-C
      ratio group among the patients with an LDL-C level of >= 100 mg/dL (p=0.011).
      However, the difference between the two groups was diminished among the patients
      with an LDL-C level of <100 mg/dL (p=0.047), and only diabetes mellitus (HR,
      2.239; p=0.009) was found to be an independent contributor to late coronary
      revascularization in these patients. CONCLUSION: The LDL-C/HDL-C ratio is an
      important contributor to the development of new coronary artery disease in
      patients with a previous history of PCI beyond the period of early restenosis,
      particularly among patients with an LDL-C level of >= 100 mg/dL.

PMID- 24739602
TI  - Glycated albumin (GA) is more advantageous than hemoglobin A1c for evaluating the
      efficacy of sitagliptin in achieving glycemic control in patients with type 2
      diabetes.
AB  - OBJECTIVE: The aim of this study was to compare the utility of hemoglobin A1c
      (HbA1c) and glycated albumin (GA) for evaluating the efficacy of the dipeptidyl
      peptidase-4 (DPP-4) inhibitor, sitagliptin, in patients with type 2 diabetes.
      METHODS: Sitagliptin (50 mg) was administered orally once daily in 67 outpatients
      with type 2 diabetes. Drug effectiveness was deemed present if the HbA1c or GA
      level decreased by 5% at week 4 and week 12 relative to the baseline value.
      RESULTS: The mean HbA1c level decreased from 8.1 +/- 1.0% at baseline to 7.8 +/-
      0.9% at week 4 and 7.2 +/- 0.8% at week 12. The mean GA level decreased from 25.0
      +/- 4.5% at baseline to 22.2 +/- 3.8% at week 4 and 20.8 +/- 3.5% at week 12. At
      week 4 and week 12, the drug was effective in 37.8% and 71.6% of the patients,
      respectively, when assessed based on changes in HbA1c, and in 83.6% and 97.0% of
      the patients, respectively, when assessed based on changes in GA. CONCLUSION: GA
      is superior to HbA1c for evaluating the efficacy of sitagliptin treatment in
      patients with type 2 diabetes.

PMID- 24739603
TI  - Association between hemoglobin and diabetes in relation to the triglycerides-to
      high-density lipoprotein cholesterol (TG-HDL) ratio in Japanese individuals: the
      Nagasaki Islands Study.
AB  - OBJECTIVE: Our previous study reported that categorizing diabetes patients
      according to the serum triglycerides-to-high-density lipoprotein cholesterol (TG
      HDL) ratio is useful for estimating the risk of atherosclerosis, as a high TG-HDL
      ratio in patients with diabetes constitutes risk factors for atherosclerosis.
      Another study showed that a high hemoglobin level is associated with the risk of
      atherosclerosis. However, no previous studies have examined the association
      between the hemoglobin level and diabetes categorized by the TG-HDL ratio. In
      order to investigate these associations, we conducted a cross-sectional study of
      3,733 (1,299 men and 2,434 women) Japanese participants 30-89 years of age
      undergoing a general health checkup. METHODS: We investigated the association
      between the hemoglobin levels and the incidence of diabetes in all subjects, who
      were divided into tertiles according to the TG-HDL ratio. Diabetes was defined as
      an HbA1c (NGSP) level of >= 6.5% and/or the initiation of glucose-lowering or
      insulin therapy. RESULTS: Of the 265 diabetes patients identified in this study,
      116 had a high TG-HDL ratio (high TG-HDL diabetes) and 71 had a low TG-HDL ratio
      (low TG-HDL diabetes). Independent from classical cardiovascular risk factors,
      the multivariate odds ratio of a 1 SD (standard deviation) increment in
      hemoglobin (1.30 g/dL for men, 1.16 g/dL for women) was 1.04 (95% confidence
      intervals (CI): 0.88-1.22) for all patients with diabetes, 1.44 (95%CI: 1.17
      1.77) for the patients with high TG-HDL diabetes and 0.67 (95%CI: 0.54-0.83) for
      the patients with low TG-HDL diabetes. CONCLUSION: The hemoglobin level is
      positively associated with high TG-HDL diabetes and inversely associated with low
      TG-HDL diabetes. These findings suggest that measuring the hemoglobin level is
      clinically relevant for estimating the risk of atherosclerosis in patients with
      diabetes categorized according to the TG-HDL ratio.

PMID- 24739604
TI  - Prompt efficacy of tolvaptan in treating hyponatremia of syndrome of
      inappropriate secretion of antidiuretic hormone (SIADH) closely associated with
      rupture of a gastric artery aneurysm.
AB  - A 78-year-old man with abdominal pain was diagnosed with a rupture of a gastric
      artery aneurysm. The serum Na level promptly decreased from 135 to 110 mmol/L
      within several days. Brain magnetic resonance angiography revealed severe
      vasoconstriction of the cerebral basilar artery and anterior cerebral artery.
      There was neither dehydration nor edema. The plasma arginine vasopressin level
      was 3.3 pg/mL, despite hypoosmolality. These findings indicated a diagnosis of
      syndrome of inappropriate secretion of antidiuretic hormone (SIADH) derived from
      severe vasoconstriction of the cerebral arteries. The administration of 7.5 mg of
      tolvaptan rapidly increased the serum Na level from 123 to 138 mmol/L within the
      first 24 hours, thereafter continuously maintaining a normal level. Treatment
      with tolvaptan corrected the patient's dilutional hyponatremia. 

PMID- 24739605
TI  - Primary intestinal follicular lymphoma and premature atherosclerosis in a
      Japanese diabetic patient with atypical familial partial lipodystrophy.
AB  - We experienced a case of primary intestinal follicular lymphoma and premature
      atherosclerosis in a diabetic patient with familial partial lipodystrophy (FPL)
      that was detected when the patient was evaluated for laparoscopic sleeve
      gastrectomy (LSG). As FPL is generally considered to be rare, FPL is often
      underdiagnosed, especially in obese patients. Therefore, the prevalence of FPL is
      higher than previous estimates. Our case illustrates that clinicians should
      perform screening for atherosclerosis and malignancy at the preoperative
      evaluation and may need to perform metabolic surgery earlier to prevent the
      development of excess truncal fat, complicated diabetes and atherosclerosis in
      patients with FPL. 

PMID- 24739606
TI  - The blood glucose level increased in parallel with the heart rate following
      cilostazol administration in three diabetic patients.
AB  - Cilostazol, a phosphodiesterase III inhibitor, is known to increase the heart
      rate; however, its effects on glucose metabolism remain unclear. We observed that
      the blood glucose level varied in parallel with the heart rate immediately after
      starting or stopping cilostazol therapy in three patients with type 2 diabetes.
      This finding indicates that cilostazol induces hyperglycemia and tachycardia in a
      portion of diabetic patients, presumably via similar pharmacological effects on
      different organs. Much more attention should be paid to the possible effects of
      cilostazol on glycemic control, including taking into consideration the risk
      benefit ratio of cilostazol use and individual circumstances. 

PMID- 24739607
TI  - Successful treatment of acute kidney injury in patients with idiopathic nephrotic
      syndrome using human atrial natriuretic Peptide.
AB  - The acute onset of idiopathic nephrotic syndrome (NS) is often accompanied by
      acute kidney injury, which can lead to congestive heart failure and lung edema.
      In this report, we present two cases of NS-induced acute kidney injury
      successfully treated with a low dose of carperitide, a human atrial natriuretic
      peptide. In combination with standard diuretic therapy and immunotherapy,
      carperitide retained the renal function and spared the need for renal replacement
      therapy, including hemodialysis. Although further investigation in clinical
      trials is required to validate these findings, carperitide may be useful for
      maintaining the renal function in cases of NS-induced acute kidney injury. 

PMID- 24739608
TI  - Pseudomesotheliomatous carcinoma due to pleural metastasis from renal pelvic
      cancer.
AB  - A 78-year-old man was referred to our department with a one-week history of
      dyspnea and coughing. A chest X-ray showed massive left pleural effusion.
      Computed tomography revealed diffuse irregular thickening of the left pleura
      similar to malignant mesothelioma and multiple nodules in both lungs. The patient
      died of respiratory failure nine days after hospitalization. An autopsy revealed
      metastasis to the pleura and lungs from urothelial carcinoma of the left kidney. 

PMID- 24739609
TI  - Bronchiolitis in a patient with ulcerative colitis treated with erythromycin.
AB  - A 47-year-old man was referred to our hospital with an abnormal shadow on a chest
      X-ray. He had a history of untreated chronic sinusitis and suspected ulcerative
      colitis (UC). Chest CT revealed a diffuse centrilobular granular shadow, while
      laboratory tests demonstrated an increased proportion of neutrophils; however, no
      microorganisms were detected in bronchoalveolar lavage fluid. Therefore,
      sinobronchial syndrome or small airway disease associated with UC was diagnosed,
      and the patient was treated with long-term erythromycin therapy. Small airway
      disease associated with UC is usually treated with steroids. Our experience shows
      that airway involvement in patients with inflammatory bowel disease can be
      treated with macrolides. 

PMID- 24739610
TI  - Multifocal encephalopathy and autoimmune-mediated limbic encephalitis following
      tocilizumab therapy.
AB  - A 63-year-old man with rheumatoid arthritis developed multifocal encephalopathy
      and limbic encephalitis following therapy with tocilizumab, a humanized anti
      interleukin-6 receptor antibody. Anti-glutamate receptor epsilon2 antibodies were
      later found to be positive in both the serum and cerebrospinal fluid. This case
      highlights the possibility of the development of encephalopathy after treatment
      with tocilizumab, which may also induce autoimmune limbic encephalitis. 

PMID- 24739611
TI  - Dropped head syndrome preceding the onset of dementia with Lewy bodies.
AB  - A 67-year-old woman developed dropped head. Her neck was severely flexed, with
      prominent cervical paraspinal muscles, although no parkinsonism was observed.
      Brain MRI showed no significant findings. We considered dystonia as the cause of
      the dropped head and administered trihexyphenidyl, an anticholinergic. After 10
      years of follow-up, remarkable psychotic symptoms, including hallucinations
      regarding insects, appeared. Following the discontinuation of trihexyphenidyl,
      the psychotic symptoms decreased but still remained. (123)I-N-isopropyl-p
      iodoamphetamine single-photon emission computed tomography ((123)I-IMP SPECT)
      revealed hypoperfusion in the bilateral occipital lobes. We diagnosed the patient
      with dementia with Lewy bodies (DLB). This case suggests that dropped head
      syndrome may precede the onset of DLB. 

PMID- 24739612
TI  - Acute spinal subdural hematoma in a patient with active systemic lupus
      erythematosus: a case report and literature review.
AB  - We herein describe a case of acute spinal subdural hematoma (SSDH) during the
      administration of high-dose corticosteroids and intravenous heparin for the
      treatment of active lupus nephritis. After SSDH was promptly diagnosed using
      magnetic resonance imaging (MRI), the patient recovered well with conservative
      treatment involving the discontinuation of heparin sodium. Although SSDH is a
      rare complication, it should be considered as a cause of neurological
      manifestations in patients with active systemic lupus erythematosus. 

PMID- 24739613
TI  - Pneumomediastinum in a patient with microscopic polyangiitis preceded by
      interstitial pneumonia.
AB  - A 73-year-old woman was diagnosed with interstitial pneumonia in 2006; however,
      the disease was not progressive. Four years later, purpura, peripheral
      neuropathy, and increased levels of myeloperoxidase anti-neutrophil cytoplasmic
      antibodies (583 EU/mL) and C-reactive protein (2.27 mg/dL) were observed, and a
      diagnosis of microscopic polyangiitis was made. Treatment with prednisolone and
      azathioprine was initiated. However, on the 35th hospital day, chest computed
      tomography showed pneumomediastinum and subcutaneous emphysema without
      aggravation of the interstitial pneumonia. To our knowledge, this is the first
      report of pneumomediastinum as a complication of microscopic polyangiitis
      associated with interstitial pneumonia. 

PMID- 24739614
TI  - Anti-citrullinated protein antibody-positive rheumatoid arthritis associated with
      RS3PE syndrome-like symptoms and an elevated serum vascular endothelial growth
      factor level in a patient with myasthenia gravis.
AB  - A 73-year-old man with a history of myasthenia gravis (MG) was diagnosed with
      rheumatoid arthritis (RA) based on a history of polyarthritis and positivity for
      anti-citrullinated protein antibodies (ACPA). He presented with a high level of
      serum vascular endothelial growth factor (VEGF) and RS3PE syndrome-like pitting
      edema in the extremities, which improved following treatment with low-dose
      prednisolone. This is an interesting case of ACPA-positive RA associated with
      RS3PE syndrome-like pitting edema and a high VEGF level. 

PMID- 24739615
TI  - Primary dengue fever associated with hemophagocytic syndrome: a report of three
      imported cases, Bordeaux, France.
AB  - The dengue virus is responsible for a wide range of symptoms that can be
      classified into two distinct syndromes: classical dengue fever and severe dengue
      fever. Among the complicating forms, hemophagocytic syndrome (HPS) has been
      previously reported in case series of patients with secondary dengue fever
      outside of endemic settings. Of note, the occurrence of HPS has not yet been
      included among the criteria for defining severe dengue fever. We herein present
      three patients with HPS related to confirmed primary dengue virus infection.
      Clinicians should therefore consider hemophagocytosis as a complication during
      severe dengue infection in naive patients. 

PMID- 24739616
TI  - Person-to-person asymptomatic infection of severe fever with thrombocytopenia
      syndrome virus through blood contact.
AB  - Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious
      disease recently discovered in northeastern and central China that is caused by a
      novel bunyavirus, severe fever with thrombocytopenia syndrome virus (SFTSV).
      Humans are primarily infected through tick bites. Four previous reports have
      discussed SFTS infection from person to person, all cases of which were
      symptomatic. In this report, we analysed the epidemiological and clinical data
      for a cluster of cases, including one case of secondary-asymptomatic infection,
      and review the literature regarding SFTSV transmission from person to person. We
      conclude that SFTSV caused the asymptomatic infections via person-to-person
      contact with infected blood. 

PMID- 24739617
TI  - Comprehensive analysis of systemically disseminated ST8/non-USA300 type community
      acquired methicillin-resistant Staphylococcus aureus infection.
AB  - Community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) is
      genetically heterogeneous and various genotypes are spreading worldwide. We
      herein report a case of systematically disseminated Japan-intrinsic CA-MRSA
      infection that was successfully treated. A genetically identical single strain
      was isolated from a total of 11 different parts of the patient's body, and the
      pathogen was found to be multilocus sequence type 8, staphylococcal cassette
      chromosome mec IV, coagulase type III and negative for both Panton-Valentine
      leukocidin and arginine catabolic mobile element. The epidemiology and
      pathogenicity of the Japan-intrinsic CA-MRSA strain remain unknown, and further
      investigation of this life-threatening organism is warranted. 

PMID- 24739618
TI  - Pediatric pulmonary tuberculoma with a solid pulmonary nodule detected on chest
      computed tomography.
AB  - A 14-year-old girl underwent a medical checkup for Mycobacterium tuberculosis
      infection because her grandmother had been diagnosed with pulmonary tuberculosis
      three months earlier. The interferon-gamma release assay (IGRA) showed a positive
      result. The patient's chest X-ray findings were normal. Chest computed tomography
      (CT) showed a single mass lesion in the right lower lobe of the lung. A sputum
      smear of acid-fast bacilli was positive; however, the polymerase chain reaction
      results for tuberculosis were negative. We diagnosed the patient with pulmonary
      tuberculosis based on the fact that she had come in contact with a tuberculosis
      patient. Six weeks later, a liquid culture examination for acid-fast bacilli was
      found to be positive and the acid-fast bacillus was identified as M.
      tuberculosis. The use of chest CT is not routinely recommended in all children
      suspected of having M. tuberculosis infection. However, IGRA-positive children
      who report frequent contact with infected individuals should undergo CT
      tomography if chest X-rays do not show any abnormal shadows. 

PMID- 24739619
TI  - Liver abscess caused by Clostridium perfringens.

PMID- 24739620
TI  - Pleural mass originating from a gonadal teratoma.

PMID- 24739621
TI  - Facial and laryngeal edema in a patient with dermatomyositis.

PMID- 24739622
TI  - Spontaneous isolated celiac artery dissection.

PMID- 24739623
TI  - Implications of streamlining theory for microbial ecology.
AB  - Whether a small cell, a small genome or a minimal set of chemical reactions with
      self-replicating properties, simplicity is beguiling. As Leonardo da Vinci
      reportedly said, 'simplicity is the ultimate sophistication'. Two diverging views
      of simplicity have emerged in accounts of symbiotic and commensal bacteria and
      cosmopolitan free-living bacteria with small genomes. The small genomes of
      obligate insect endosymbionts have been attributed to genetic drift caused by
      small effective population sizes (Ne). In contrast, streamlining theory
      attributes small cells and genomes to selection for efficient use of nutrients in
      populations where Ne is large and nutrients limit growth. Regardless of the cause
      of genome reduction, lost coding potential eventually dictates loss of function.
      Consequences of reductive evolution in streamlined organisms include atypical
      patterns of prototrophy and the absence of common regulatory systems, which have
      been linked to difficulty in culturing these cells. Recent evidence from
      metagenomics suggests that streamlining is commonplace, may broadly explain the
      phenomenon of the uncultured microbial majority, and might also explain the
      highly interdependent (connected) behavior of many microbial ecosystems.
      Streamlining theory is belied by the observation that many successful bacteria
      are large cells with complex genomes. To fully appreciate streamlining, we must
      look to the life histories and adaptive strategies of cells, which impose minimum
      requirements for complexity that vary with niche. 

PMID- 24739624
TI  - Molecular and biogeochemical evidence for methane cycling beneath the western
      margin of the Greenland Ice Sheet.
AB  - Microbial processes that mineralize organic carbon and enhance solute production
      at the bed of polar ice sheets could be of a magnitude sufficient to affect
      global elemental cycles. To investigate the biogeochemistry of a polar subglacial
      microbial ecosystem, we analyzed water discharged during the summer of 2012 and
      2013 from Russell Glacier, a land-terminating outlet glacier at the western
      margin of the Greenland Ice Sheet. The molecular data implied that the most
      abundant and active component of the subglacial microbial community at these
      marginal locations were bacteria within the order Methylococcales (59-100% of
      reverse transcribed (RT)-rRNA sequences). mRNA transcripts of the particulate
      methane monooxygenase (pmoA) from these taxa were also detected, confirming that
      methanotrophic bacteria were functional members of this subglacial ecosystem.
      Dissolved methane ranged between 2.7 and 83 MUM in the subglacial waters
      analyzed, and the concentration was inversely correlated with dissolved oxygen
      while positively correlated with electrical conductivity. Subglacial microbial
      methane production was supported by delta(13)C-CH4 values between -640/00 and 
      620/00 together with the recovery of RT-rRNA sequences that classified within the
      Methanosarcinales and Methanomicrobiales. Under aerobic conditions, >98% of the
      methane in the subglacial water was consumed over ~30 days incubation at ~4 
      degrees C and rates of methane oxidation were estimated at 0.32 MUM per day. Our
      results support the occurrence of active methane cycling beneath this region of
      the Greenland Ice Sheet, where microbial communities poised in oxygenated
      subglacial drainage channels could serve as significant methane sinks. 

PMID- 24739625
TI  - Dynamics of bacterial community succession in a salt marsh chronosequence:
      evidences for temporal niche partitioning.
AB  - The mechanisms underlying community assembly and promoting temporal succession
      are often overlooked in microbial ecology. Here, we studied an undisturbed salt
      marsh chronosequence, spanning over a century of ecosystem development, to
      understand bacterial succession in soil. We used 16S rRNA gene-based quantitative
      PCR to determine bacterial abundance and multitag 454 pyrosequencing for
      community composition and diversity analyses. Despite 10-fold lower 16S rRNA gene
      abundances, the initial stages of soil development held higher phylogenetic
      diversities than the soil at late succession. Temporal variations in phylogenetic
      beta-diversity were greater at initial stages of soil development, possibly as a
      result of the great dynamism imposed by the daily influence of the tide,
      promoting high immigration rates. Allogenic succession of bacterial communities
      was mostly driven by shifts in the soil physical structure, as well as variations
      in pH and salinity, which collectively explained 84.5% of the variation
      concerning community assemblage. The community assembly data for each
      successional stage were integrated into a network co-occurrence analysis,
      revealing higher complexity at initial stages, coinciding with great dynamism in
      turnover and environmental variability. Contrary to a spatial niche-based
      perspective of bacterial community assembly, we suggest temporal niche
      partitioning as the dominant mechanism of assembly (promoting more phylotype co
      occurrence) in the initial stages of succession, where continuous environmental
      change results in the existence of multiple niches over short periods of time. 

PMID- 24739626
TI  - Comparative transcriptomics of two environmentally relevant cyanobacteria reveals
      unexpected transcriptome diversity.
AB  - Prochlorococcus is a genus of abundant and ecologically important marine
      cyanobacteria. Here, we present a comprehensive comparison of the structure and
      composition of the transcriptomes of two Prochlorococcus strains, which, despite
      their similarities, have adapted their gene pool to specific environmental
      constraints. We present genome-wide maps of transcriptional start sites (TSS) for
      both organisms, which are representatives of the two most diverse clades within
      the two major ecotypes adapted to high- and low-light conditions, respectively.
      Our data suggest antisense transcription for three-quarters of all genes, which
      is substantially more than that observed in other bacteria. We discovered
      hundreds of TSS within genes, most notably within 16 of the 29 prochlorosin
      genes, in strain MIT9313. A direct comparison revealed very little conservation
      in the location of TSS and the nature of non-coding transcripts between both
      strains. We detected extremely short 5' untranslated regions with a median length
      of only 27 and 29 nt for MED4 and MIT9313, respectively, and for 8% of all
      protein-coding genes the median distance to the start codon is only 10 nt or even
      shorter. These findings and the absence of an obvious Shine-Dalgarno motif
      suggest that leaderless translation and ribosomal protein S1-dependent
      translation constitute alternative mechanisms for translation initiation in
      Prochlorococcus. We conclude that genome-wide antisense transcription is a major
      component of the transcriptional output from these relatively small genomes and
      that a hitherto unrecognized high degree of complexity and variability of gene
      expression exists in their transcriptional architecture. 

PMID- 24739627
TI  - Deterministic processes guide long-term synchronised population dynamics in
      replicate anaerobic digesters.
AB  - A replicate long-term experiment was conducted using anaerobic digestion (AD) as
      a model process to determine the relative role of niche and neutral theory on
      microbial community assembly, and to link community dynamics to system
      performance. AD is performed by a complex network of microorganisms and process
      stability relies entirely on the synergistic interactions between populations
      belonging to different functional guilds. In this study, three independent
      replicate anaerobic digesters were seeded with the same diverse inoculum,
      supplied with a model substrate, alpha-cellulose, and operated for 362 days at a
      10-day hydraulic residence time under mesophilic conditions. Selective pressure
      imposed by the operational conditions and model substrate caused large
      reproducible changes in community composition including an overall decrease in
      richness in the first month of operation, followed by synchronised population
      dynamics that correlated with changes in reactor performance. This included the
      synchronised emergence and decline of distinct Ruminococcus phylotypes at day
      148, and emergence of a Clostridium and Methanosaeta phylotype at day 178, when
      performance became stable in all reactors. These data suggest that many dynamic
      functional niches are predictably filled by phylogenetically coherent populations
      over long time scales. Neutral theory would predict that a complex community with
      a high degree of recognised functional redundancy would lead to stochastic
      changes in populations and community divergence over time. We conclude that
      deterministic processes may play a larger role in microbial community dynamics
      than currently appreciated, and under controlled conditions it may be possible to
      reliably predict community structural and functional changes over time. 

PMID- 24739629
TI  - A field evaluation of two vaccines against Mycoplasma hyopneumoniae infection in
      pigs.
AB  - BACKGROUND: A field trial was carried out with two Mycoplasma hyopneumoniae
      vaccines in order to investigate the benefit of vaccination under field
      conditions in modern Danish pig production facilities with pigs being positive
      for M. hyopneumoniae. The M. hyopneumoniae infection of the herd was confirmed
      through blood samples that were positive for antibodies against M. hyopneumoniae
      combined with gross lesions of the lungs related to M. hyopneumoniae at slaughter
      and detection of M. hyopneumoniae by polymerace chain reaction in these lesions.
      RESULTS: A total of 2,256 pigs from two herds were randomly divided into three
      groups. Group 1 received 2 mL ThoroVAX(r)VET, Group 2 received 1 mL
      Ingelvac(r)MycoFLEX, and Group 3 was a non-vaccinated control group. The
      vaccination was performed by a person who was not involved in the rest of the
      trial and vaccination status thereby blinded to the evaluators.The prevalence of
      lung lesions related to M. hyopneumoniae were significantly lower for pigs
      vaccinated with ThoroVAX(r)VET but not for pigs vaccinated with
      Ingelvac(r)MycoFLEX(r), when compared to non-vaccinated pigs. There was no
      significant effect of vaccination on growth rate, antibiotic consumption or
      mortality. CONCLUSION: This trial demonstrated that vaccination with Thoro(r)VAX
      VET was effective in reducing the prevalence of lung lesion in pig units infected
      with M. hyopneumoniae.

PMID- 24739628
TI  - Interspecies competition triggers virulence and mutability in Candida albicans
      Pseudomonas aeruginosa mixed biofilms.
AB  - Inter-kingdom and interspecies interactions are ubiquitous in nature and are
      important for the survival of species and ecological balance. The investigation
      of microbe-microbe interactions is essential for understanding the in vivo
      activities of commensal and pathogenic microorganisms. Candida albicans, a
      polymorphic fungus, and Pseudomonas aeruginosa, a Gram-negative bacterium, are
      two opportunistic pathogens that interact in various polymicrobial infections in
      humans. To determine how P. aeruginosa affects the physiology of C. albicans and
      vice versa, we compared the proteomes of each species in mixed biofilms versus
      single-species biofilms. In addition, extracellular proteins were analyzed. We
      observed that, in mixed biofilms, both species showed differential expression of
      virulence proteins, multidrug resistance-associated proteins, proteases and cell
      defense, stress and iron-regulated proteins. Furthermore, in mixed biofilms, both
      species displayed an increase in mutability compared with monospecific biofilms.
      This characteristic was correlated with the downregulation of enzymes conferring
      protection against DNA oxidation. In mixed biofilms, P. aeruginosa regulates its
      production of various molecules involved in quorum sensing and induces the
      production of virulence factors (pyoverdine, rhamnolipids and pyocyanin), which
      are major contributors to the ability of this bacterium to cause disease.
      Overall, our results indicate that interspecies competition between these
      opportunistic pathogens enhances the production of virulence factors and
      increases mutability and thus can alter the course of host-pathogen interactions
      in polymicrobial infections. 

PMID- 24739630
TI  - Extraintestinal manifestations and complications in inflammatory bowel disease:
      from shared genetics to shared biological pathways.
AB  - BACKGROUND: The clinical presentation of the inflammatory bowel diseases (IBD) is
      extremely heterogenous and is characterized by various extraintestinal
      manifestations and complications (EIM). Increasing genetic insight for IBD and
      EIM shows multiple shared susceptibility loci. We hypothesize that, next to these
      overlapping genetic risk loci, distinct disease pathways are shared between IBD
      and EIM. METHODS: The overlapping genetic risk loci for IBD and its EIM were
      searched in literature. We assessed shared disease pathways by performing an
      extensive pathway analysis by protein-protein interaction and cotranscriptional
      analysis, using both publicly available and newly developed databases. RESULTS:
      Reliable genetic data were available for primary sclerosing cholangitis,
      ankylosing spondylitis, decreased bone mineral density, colorectal carcinoma,
      gallstones, kidney stones, and deep venous thrombosis. We found an extensive
      overlap in genetic risk loci, especially for IBD and primary sclerosing
      cholangitis and ankylosing spondylitis. We identified 370 protein-protein
      interactions, of which 108 are statistically specific. We identified 446
      statistically specific cotranscribed gene pairs. The interactions are shown to
      cluster in specific biological pathways. CONCLUSIONS: We show that the
      pathogenetic overlap between IBD and its EIM extends beyond shared risk genes to
      distinctive shared biological pathways. We define genetic background as a risk
      factor for IBD-EIM alongside known mechanisms such as malabsorption and
      medication. Clustering patients based on distinctive pathways may enable
      stratification of patients to predict development of EIM.

PMID- 24739631
TI  - Multigene analysis unveils distinctive expression profiles of helper T-cell
      related genes in the intestinal mucosa that discriminate between ulcerative
      colitis and Crohn's disease.
AB  - BACKGROUND: Although the involvement of helper T (Th) and regulatory T (Treg)
      cell-related immune molecules in pathogenesis of inflammatory bowel disease (IBD)
      is widely accepted, no discriminatory mucosal expression profiles of these
      molecules between ulcerative colitis (UC) and Crohn's disease (CD) have been
      clarified. METHODS: Mucosal expression of 17 cytokines and transcription factors
      related to Th1, Th2, Th17, and Treg were measured by quantitative PCR in
      endoscopic biopsies from inflamed (40 from UC [UCI] and 20 from CD [CDI]) and
      noninflamed (47, 22, and 25 from UC, CD, and controls, respectively) colon or
      ileum. The discriminatory power of these markers to differentiate between the 2
      diseases was evaluated by linear discriminant analysis and, unsupervised,
      principal component analysis. RESULTS: By univariate analysis, many targets were
      markedly increased in inflamed versus noninflamed areas. However, marker
      expression was almost comparable between UCI and CDI, with the largest difference
      in UCI-predominant interleukin (IL) 21 and IL-13 with area under the receiver
      operating characteristic curve (AUC) values of 0.704 and 0.664, respectively. In
      contrast, combinations of 2 to 7 markers improved UCI versus CDI discrimination
      with AUC = 0.875 to 0.975. Among these, a 5-maker set (interferon-gamma, IL-12
      p35, T-bet, GATA3, and IL-21) demonstrated an AUC of 0.949 and a
      misclassification rate of 8.3%. Principal component analysis also markedly
      separated UCI and CDI. CONCLUSIONS: Inflamed mucosae from UC and CD could be
      discriminated with high accuracy using combinations of Th cell-related markers.
      Multigene analysis, possibly reflecting the underlying pathogenesis, is expected
      to be useful for diagnosis, monitoring and further defining distinctive
      characteristics in inflammatory bowel disease.

PMID- 24739632
TI  - Vitamin B12 deficiency in inflammatory bowel disease: prevalence, risk factors,
      evaluation, and management.
AB  - BACKGROUND: Management of vitamin B(12) (cobalamin, Cbl) deficiency in
      inflammatory bowel disease (IBD) is often not evidenced-based because of
      uncertainty on whether it causes enough malabsorption to result in clinical
      disease. This systematic review examines whether IBD predisposes to Cbl
      deficiency. We provide an approach to the management of abnormal Cbl values in
      IBD based on current literature and consensus-based guidelines. METHODS: An
      extensive search of the Ovid MEDLINE and EMBASE databases by independent
      reviewers identified 42 articles with a total of 3732 patients evaluating Cbl
      deficiency in IBD. RESULTS: Crohn's disease without ileal resection, regardless
      of disease location in the ileum, did not increase the risk for Cbl deficiency.
      Ileal resections greater than 30 cm were associated with Cbl deficiency in
      Crohn's disease, whereas those less than 20 cm were not. The effects of 20 to 30
      cm resections were inconsistent. Ulcerative colitis did not predispose to
      deficiency. All studies failed to use confirmatory biomarker testing as
      stipulated by diagnostic guidelines for Cbl deficiency. CONCLUSIONS: This
      literature does not support an association of Crohn's disease in general,
      regardless of ileal involvement, with Cbl deficiency. Only ileal resections
      greater than 20 cm in Crohn's disease predispose to deficiency and warrant
      treatment. Based on these findings, we suggest a diagnostic and therapeutic
      algorithm. All findings and recommendations require verification in further
      studies using confirmatory biomarkers as per diagnostic guidelines for Cbl
      deficiency. Serum Cbl levels alone are likely insufficient to diagnose deficiency
      in asymptomatic patients.

PMID- 24739633
TI  - Mucosal toll-like receptor 3-dependent synthesis of complement factor B and
      systemic complement activation in inflammatory bowel disease.
AB  - BACKGROUND: Recent studies link Toll-like receptor 3 (TLR3) to the pathogenesis
      of inflammatory bowel disease (IBD). Screening TLR3-agonist response in an
      intestinal epithelial cell line, we found complement factor B mRNA (CFB) potently
      upregulated and went on to further study localization of complement factor B
      synthesis and systemic activation of complement in ulcerative colitis and Crohn's
      disease. METHODS: In a transcriptome analysis of poly (I:C) stimulated HT-29
      cells, we found CFB highly upregulated downstream of TLR3. We sought to confirm
      CFB upregulation in a microarray gene expression analysis on colonic biopsies
      from an IBD population (n = 133). Immunohistochemical staining and in situ
      hybridization were done to identify cellular sources of factor B and CFB.
      Systemic complement activation was assessed in plasma (n = 18) using neoepitope
      based enzyme linked immunosorbent assay. RESULTS: CFB mRNA and protein were
      abundantly expressed in the colonic epithelial cell line, and synthesis enhanced
      by the poly (I:C) TLR3 ligand. In inflamed versus normal colonic mucosa of
      ulcerative colitis and Crohn's disease, CFB mRNA was the most significantly
      overexpressed gene and the mRNA abundance ratio was among the 50 highest.
      Epithelial cells were the dominating site of factor B expression. Systemic
      complement activation was significantly higher in active than in nonactive IBD.
      CONCLUSIONS: This study is the first to link TLR3 to activation of the
      alternative complement pathway. Complement factor B is potently upregulated
      locally in IBD in addition to having a possible central role in systemic
      complement activation. This suggests a prominent role for complement in IBD
      pathogenesis.

PMID- 24739634
TI  - Astragalus saponin attenuates the expression of fibrosis-related molecules in
      irradiated cardiac fibroblasts.
AB  - The main pathological change of radiation-induced heart disease is fibrosis.
      Emerging evidence has indicated that Astragalus membranaceus and its extractant,
      Astragalus saponin (AST), were used for treating fibrosis diseases. In the
      present study, the effects of AST on fibrosis damage induced by irradiation were
      determined. After being irradiated with 1 or 2-Gy X-rays, obvious changes of
      endoplasmic reticulum morphology were observed in cardiac fibroblasts (CFs),
      suggesting that its protein processing function was imbalanced, which indirectly
      indicated that fibrosis damage was caused by irradiating CFs. The expression
      levels of TGF-beta1 and collagen I (Col-1) were increased at 48-h post
      irradiation. Administration of 20 MUg/ml AST reduced the production of reactive
      oxygen species in irradiated CFs and decreased the expression of Col-1, TGF
      beta1, and p-Smad2/3. Polymerase chain reaction (PCR)-array analysis showed that
      there were ~30 genes which were mainly classified into extracellular matrix,
      remodeling enzymes, inflammatory cytokines/chemokines, and TGF-beta superfamily,
      were up-regulated after treatment with 1-Gy X-ray, whereas most of these genes
      were down-regulated when pretreated with 20 MUg/ml of AST. In addition, TIMP1 and
      Smad7 genes that were down-regulated after treatment with 1-Gy X-ray were up
      regulated when pretreated with 20 MUg/ml of AST. In conclusion, radiation-induced
      fibrosis damage was observed at a cellular level. AST attenuated this fibrosis
      damage effect in irradiated CFs and this anti-fibrosis effect may be closely
      related to its antioxidant action. The involvement of fibrosis-related molecules
      in irradiated CFs was systematically demonstrated by a PCR array for the first
      time. AST reversed the expression of the majority of genes changed by
      irradiation, which further confirmed its anti-fibrosis effect.

PMID- 24739635
TI  - Human mesenchymal stem cells with adenovirus-mediated TRAIL gene transduction
      have antitumor effects on esophageal cancer cell line Eca-109.
AB  - The apoptotic ligand TNF-related apoptosis-inducing ligand (TRAIL) is believed to
      be a promising candidate for cancer gene therapy, yet gene therapy strategies to
      tackle this disease systemically are often impaired by inefficient delivery of
      the vector to the tumor tissue. Mesenchymal stem cells (MSCs) have been shown to
      home to tumor sites and could potentially act as a shield and vehicle for an
      antitumor gene therapy vector. Here, we used an adenoviral vector expressing
      TRAIL to transduce MSCs and studied the apoptosis-inducing activity of these
      TRAIL-carrying MSCs on esophageal cancer cell Eca-109. Our results showed that,
      in vitro, TRAIL-expressing MSCs were able to inhibit proliferation and induce
      apoptosis in Eca-109 cells by an MTT assay, co-culture experiments and flow
      cytometry analysis. In vivo, TRAIL-expressing MSCs also displayed an ability to
      inhibit tumor growth in an Eca-109 xenograft mouse model. Together, our findings
      indicated that the gene therapy strategy of MSCs-based TRAIL gene delivery has a
      wide potential value for improving the treatment of esophageal cancer.

PMID- 24739636
TI  - [Focus on the application of digital techniques in obstetrics and gynecology].

PMID- 24739637
TI  - [Reconstruction and characteristics of the three-dimensional models of uterine
      arterial vascular network for healthy females aged 20-26 years].
AB  - OBJECTIVE: To analyze the characteristics of anatomy and blood distribution of
      uterine arterial vascular network in vivo for healthy women aged 20-26 years by
      reconstructing the digital three-dimensional models based on computerized
      tomographic angiography (CTA) scanning technology. METHODS: From August to
      December 2012, a total of 25 female volunteers aged 20-26 years were recruited.
      All of them accepted CTA scanning. Their datasets were collected for
      reconstructing the digital three-dimension models of normal uterine arterial
      vascular network by using Mimics Version 10.01 software. After recognizing the
      supply arteries of each part of uterus, the three dimension models were divided
      into corpus and cervix arterial vascular network, left and right corpus arterial
      vascular network, left and right cervical artery vasc ular network and then
      calculated the proportion of vascular volume. RESULTS: Digital three-dimension
      models of normal uterine arterial vascular network of 25 cases were successfully
      reconstructed, which clearly showed the structure of the uterine artery and its
      branches at all levels. Under normal physiological conditions, vascular network
      of corpus developed in 21 cases (84%, 21/25). In these cases, bilateral vascular
      network were developed and supplied by the ipsilateral uterine artery
      respectively, where the distribution of vascular were bilateral balanced in 18
      cases and unilateral predominant in 3 cases.However, 4 cases (16%, 4/25) of
      vascular network of corpus were not developed. There were not statistically
      significant of vascular network volume between both sides of uterine corpus of 25
      cases digital three dimension models of normal uterine arterial vascular network
      (t = 1.817, P = 0.077). The cervical arterial vascular networks didn't develop in
      23 cases (92%, 23/25), whereas it developed in 2 cases (8%, 2/25). CONCLUSIONS:
      This study successfully reconstructed the three dimensional models of uterine
      arterial vascular network for healthy females aged 20-26 years, confirming that
      the overall normal uterine vascular network distribution has the characteristics
      of bilateral, ipsilateral blood tendentious and balanced. But the cervical
      vascular network is rarely developing.

PMID- 24739638
TI  - [Application of in vivo pelvis and abdominal-pelvic arterial network digital
      three-dimensional model for uterine artery embolization in surgical approach
      planning].
AB  - OBJECTIVE: To investigate the construction and significance of in vivo pelvis and
      abdominal-pelvic arterial vascular network in digital three-dimensional (3D)
      model for uterine artery embolization (UAE) in the application of surgical
      approach planning based on computerized tomographic angiography(CTA). METHODS: A
      series of digital imaging and communications in medicine 3.0 (Dicom 3.0) were
      obtained from a woman with myoma of uterus by CTA scanning. Then the software
      Mimics Version 10.01 was used to construct the pelvic and the arterial vascular
      network 3D model. RESULTS: The digital model could clearly display the abdominal
      aorta, bilateral common iliac arteries, left and right external iliac artery,
      internal iliac artery and its branches around the stage; the right uterine artery
      emitted in the inferior gluteal artery opening below 15.91 mm, the left uterine
      artery in inferior gluteal artery below the opening of 15.21 mm, the adjacent
      artery of internal pudendal artery. At the same time, the artery length and angle
      of bifurcation were accurately measured. The bifurcation angle of abdominal aorta
      in fifth lumbar vertebral body edge, was 66.58 degrees , the bifurcation angle of
      right internal iliac artery was 46.23 degrees , the length of right common iliac
      artery was 51.43 mm, the bifurcation angle between left and external internal
      iliac artery was 36.45 degrees , the length of left common iliac artery and 67.50
      mm. According to the preoperative approach planning, guided wire across the
      inferior gluteal artery to the lower 15.00 mm and rotating digital subtraction
      angiography (DSA) tube, could clearly display the uterine artery opening outward
      by rotating guide wire, which was relatively easy to enter the uterine artery.
      CONCLUSION: The female pelvic arterial network model in vivo could be
      successfully constructed by using Mimics Version 10.01 software with database
      collected through CTA, which may contribute to the materialization of digital
      models and be used for preoperative surgical simulator.

PMID- 24739639
TI  - [Significance of digital three-dimensional reconstruction techniques in the
      diagnosis of pelvic mass].
AB  - OBJECTIVE: To explore the significance of digital three-dimensional
      reconstruction techniques in the diagnosis of female pelvic mass. METHODS:
      Original computed tomographic angiography (CTA) datasets of 72 patients with
      pelvic mass who were hospitalized in Southern Hospital of Southern Medical
      University from October 2009 to October 2012 were collected. All cases were
      undergone the B-mode ultrasound and CTA examination, the datasets were input into
      the Mimics Version 10.01 software respectively to construct digital three
      dimensional models of pelvic, arterial blood network, pelvic mass and organs.On
      the basis of without knowing the diagnosis of the disease on CTA, two
      gynecologists gave the final diagnosis of the disease after observing and
      analyzing the supply blood vessels and the relationship between the adjacent
      organs of pelvic mass through rotate the three-dimensional model by single-blind
      method. Define the postoperative pathological diagnosis as the standard, and
      compare the coincidence rate between the postoperative pathological diagnosis
      with diagnosis results on different inspections (including B ultrasound results,
      CTA results or the diagnosis on the three-dimensional model of pelvic mass).
      RESULTS: We successfully reconstructed 72 patients' three-dimensional model which
      could clearly display anatomic structure of pelvic bone, abdomen and pelvic
      arterial branches at different levels and the anatomic relationship between the
      mass and main organs in the pelvis. In all cases, 56 of them preoperative B-mode
      ultrasound examination were consistency with the postoperative pathological
      diagnosis, the coincidence rate was 78%, the preoperative CTA inspection results
      of 58 patients were consistency with the postoperative pathological diagnosis,
      the coincidence rate was 81%. While the diagnosis rate of 66 patients on the
      basis of digital three-dimensional model were consistency with that of the
      postoperative pathological diagnosis, the coincidence rate was 92%. Compared the
      compliance rate between diagnosis of pelvic mass based on the digital three
      dimensional model and preoperative B-mode ultrasound, there were significant
      difference(P = 0.021).While compared with the preoperative CTA examination, there
      was not significant difference (P = 0.054). CONCLUSION: The pelvic three
      dimensional models in vivo constructed by the digital three-dimensional
      reconstruction technique could visually display the source of the blood supply
      and the relationship between the pelvic organs, and guide to diagnosis and assess
      preoperatively.

PMID- 24739640
TI  - [Application value of three-dimensional female pelvic visualization modeling on
      transvaginal gynecological ultrasound imaging].
AB  - OBJECTIVE: To explore the application value of three-dimensional (3D) female
      pelvic visualization model on transvaginal gynecological ultrasound imaging.
      METHODS: The second digital Chinese woman visible human datasets was selected,
      and a female pelvicvoxel-based model was constructed in Amira software for analog
      simulation combined with transvaginal gynecological ultrasound. The main
      structures and the space position variation of female pelvic cavity were
      observed, and the comparison study with conventional section of ultrasound was
      carried out. RESULTS: A high accuracy 3D visualization model of female pelvic was
      successfully constructed, and the anatomy structures can be dynamically and
      clearly displayed in any section orientation. An analog simulation research was
      carried out according to the scan mode of gynecological ultrasound, and a series
      of high resolution images consistent with scan sections of dynamic ultrasound
      were obtained, which had provided the optimal scan pathway for the fast
      inspection of the uterus, fallopian tubes and ovaries. CONCLUSION: The 3D female
      pelvic visualization model based on digital Chinese woman human datasets has
      provided detailed and accurate anatomy information for transvaginal gynecological
      ultrasound imaging, which could be the benefit for doctors to understand the
      ultrasound images of female pelvic, as well as the accurate positioning ability
      to the lesions of female pelvic cavity.

PMID- 24739641
TI  - [Maternal and fetal outcomes in pregnant patients undergoing cardiac surgery with
      cardiopulmonary bypass].
AB  - OBJECTIVE: To evaluate the optimal management of cardiac surgery during
      pregnancy, and the maternal and fetal outcomes in pregnant patients undergoing
      cardiac surgery with the use of cardiopulmonary bypass. METHODS: Nine pregnant
      women with heart diseases were identified, who underwent cardiac surgery with
      cardiopulmonary bypass between January 2002 and March 2013. Patient charts were
      reviewed for pregnant age, types of heart diseases, surgical indication,
      parameters of cardiopulmonary bypass, and maternal and fetal outcomes. RESULTS:
      Among 9 patients, there were 4 cases of valvular heart disease (two of rheumatic
      heart disease complicated with subacute bacterial endocarditis and heart failure,
      one of mechanical prosthetic valves flap after mitral replacement, one of severe
      aortic stenosis), one case of aortic dissection, three cases with atrial myxoma,
      and one case with tetralogy of Fallot. The New York Heart Association (NYHA)
      functional classification: there were three cases with class I, two with class
      II, two with class III, and two with class IV. Heart surgeries were performed
      from 9 to 39 weeks gestation. Five patients underwent heart surgery with
      cardiopulmonary bypass combined with cesarean section. The other 4 patients
      terminated pregnancies after heart surgeries, two of whom underwent uterine
      curettage in first trimester, one induction of labor in second trimester, and one
      continued to be pregnant until 37 weeks' gestation. Seven patients were alive.
      Nine fetal outcomes were included two with artificial abortion, one with
      induction of labor and one with cesarean section in second trimester, two of
      premature labor and three of full-term labor with cesarean section in third
      trimester. Five newborns were no malformation, four of whom were alive.
      CONCLUSION: Cardiopulmonary bypass can be used safely with satisfactory maternal
      and fetal outcomes in pregnant patients with heart disease undergoing cardiac
      surgery.

PMID- 24739642
TI  - [Thyroid hormone changes in women with pre-eclampsia and its relationship with
      the presence of pre-eclampsia].
AB  - OBJECTIVE: To study thyroid hormone changes in women with pre-eclampsia patients,
      the characteristics of thyroid disease and its relationship with pre-eclampsia.
      METHODS: From May 2011 to December 2012 171 patients with pre-eclampsia who
      delivered in Shengjing Hospital of China Medical University were recruited as pre
      eclampsia(PE) group, among which 114 cases were defined as early onset pre
      eclampsia (EP) group and 57 cases were defined as late onset pre-eclampsia (LP)
      group. And 171 healthy women with same age and same stage of pregnancy were
      selected as the control group. Their blood pressures were normal and they had no
      obstetrical complications. Serum thyrotropin (TSH), free triiodothyronine (FT3)
      and free thyroxine(FT4) levels were determined by solid-phase chemiluminescent
      enzyme immunoassay method (CMIA). Thyroid peroxidase antibody (TPOAb) and
      thyroglobulin antibody (TGAb) were measured by electro-chemiluminescent assay
      (ECLIA). The positive rate was calculated (TPOAb > 5.6 U/L, TGAb > 4.1 U/L were
      defined as positive result). The relationship between TSH, FT3, FT4 level and
      blood pressure was analyzed in women with pre-eclampsia. RESULTS: (1) The median
      values of TSH, FT4 and FT3 in PE group were 3.4 mU/L, (12.0 +/- 3.0) pmol/L and
      (3.9 +/- 0.9) pmol/L. In the control group, they were 1.9 mU/L, (13.4 +/- 2.4)
      and (5.0 +/- 1.3) pmol/L. There were statistically significant differences
      between the two groups(P < 0.01). In EP group, the median values of TSH, FT4 and
      FT3 were 3.3 mU/L, (12.1 +/- 3.4) pmol/L and (3.8 +/- 0.9) pmol/L. The
      differences between EP group and the control group were statistically significant
      (P < 0.01). In LP group, the median values of TSH, FT4 and FT3 were 3.4 mU/L,
      (11.9 +/- 3.1) pmol/L and (3.9 +/- 1.0)pmol/L. There were statistically
      significant differences compared to the control group(P < 0.01). While there was
      no difference between EP group and LP group (P > 0.05). (2) The positive rate of
      TPOAb and TGAb in PE group were 15.2% (26/171) and 21.6% (37/171), and were 12.3%
      (21/171) and 14.6% (25/171) in the control group. There was statistically
      significant difference in the TGAb positive rate (P < 0.01), but the difference
      in TPOAb positive rate was not statistically different (P > 0.05). The TPOAb
      positive rates in EP group and LP group were 12.3% (14/114) and 21.1% (12/57),
      respectively, with no statistically significant difference (P > 0.05). And the
      positive rates of TGAb in EP group and LP group were 21.9% (25/114) and 21.1%
      (12/57) , respectively, with no statistically significant difference (P > 0.05).
      The positive rate of TPOAb in LP group and in the control group had statistically
      significant difference (P < 0.01). (3) The morbidity of thyroid disease in PE
      group and in the control group were 47.4% (81/171) and 16.4% (28/171) , with
      statistically significant difference (P < 0.01). (4) The morbidity of subclinical
      hypothyroidism or hypothyroidism in PE group and in the control group were 45.0%
      (77/171) and 16.4% (28/171) , with statistically significant difference(P <
      0.01). (5) The morbidity of subclinical hyperthyroidism in PE group and in the
      control group were 2.3% (4/171) and 1.8% (3/171) , with no statistically
      significant difference (P > 0.05). (6) In PE group, women with TSH level of 0.3
      3.3 mU/L had systolic pressure of (170 +/- 21) mmHg (1mmHg = 0.133 kPa) and
      diastolic pressure of (112 +/- 15) mmHg; women with TSH > 3.3 mU/L had systolic
      pressure of (166 +/- 21) mmHg and diastolic pressure of (109 +/- 13) mmHg. There
      was no statistically significant difference (P > 0.05). But the diastolic
      pressure in EP group and LP group had statistically significant difference (P <
      0.01). In PE group, no correlation was found among TSH, FT4 levels and systolic
      pressure, diastolic pressure (P > 0.05). FT3 level was negatively correlated to
      diastolic pressure (r = -0.172, P = 0.023) . CONCLUSIONS: It is common that pre
      eclampsia is complicated with thyroid dysfunction, mainly subclinical
      hypothyroidism. Thus it is nessesary to test thyroid hormone and thyroid
      antibodies in women with pre-eclampsia. The decrease of FT3 and FT4, the increase
      of TSH and the presence of TPOAb and TGAb are related with the presence of pre
      eclampsia.

PMID- 24739643
TI  - [Expression of stromal cell-derived factor-1 in endometriosis by steroid receptor
      coactivators on steroid hormone].
AB  - OBJECTIVES: To study the expression patterns of steroid receptor coactivators
      (SRC) and steroid-induced stromal cell-derived factor-1 (SDF-1) in endometriosis,
      and to explore the roles of SRC in the steroid-induced SDF-1 expression
      endometriosis. METHODS: From May 2010 to October 2012, 16 endometriosis cases at
      stages III or IV according to the revised American Society for Reproductive
      Medicine classification undergoing surgery in the First Affiliated Hospital to
      Nanjing Medical University were enrolled in this study. Their ectopic endometrium
      were from ovarian endometriomata which were identified pathologically with 9
      cases at proliferative phase and 7 cases at secretory phase. The normal
      endometrium were acquired from the healthy women with normal menstrual cycle (n =
      10, proliferative phase = 5, secretory phase = 5). The mRNA levels of SRC and SDF
      1alpha during the menstrual cycle were detected by quantitative real-time
      polymerase chain reaction. Ectopic endometrium stromal cells were purified and
      cultured in medium containing 17beta-estradiol (10(-8) mol/L) or 17beta-estradiol
      (10(-8) mol/L) + progesterone (10(-6) mol/L). At 24, 48, 72 and 96 hours, the
      supernatants were collected to measure SDF-1alpha expression by ELISA. Ectopic
      endometrium stromal cells were transfected respectively with siRNA of SRC-1 and
      SRC-2 using lipofectamine. Two days after transfection, 17beta-estradiol (10(-8)
      mol/L) or 17beta-estradiol (10(-8) mol/L) + progesterone (10(-6) mol/L) were
      added into the media. On the third day after the steroid hormones treatment, the
      media were collected to quantify SDF-1alpha expression with ELISA. RESULTS: (1)
      Cyclical changes: the SRC-1, SRC-2 and SDF-1alpha showed marked cyclic
      differences in normal endometrium (P < 0.05). In proliferative phase and
      secretory phase, the SRC-1, SRC-2 and SDF-1alpha were 5.6 +/- 1.2, 3.8 +/- 1.1,
      2.7 +/- 0.5 and 2.6 +/- 1.0, 2.1 +/- 1.0, 1.6 +/- 0.5, respectively. There was no
      periodic variation in the expression of SRC-1, SRC-2 and SDF-1alpha in ectopic
      endometrium throughout the menstrual cycle. (2) Steroid-induced SDF-1alpha
      expression in ectopic endometrium stromal cells: the 17beta-estradiol-induced SDF
      1alpha expression was (1 803 +/- 196), (2 272 +/- 261) and (2 162 +/- 258) ng/L
      at 48, 72 and 96 hours . At the same time points, the SDF-1alpha expression
      induced by 17beta-estradiol and progesterone was (1 307 +/- 150), (1 518 +/- 301)
      and (1 550 +/- 144) ng/L, respectively. There was significant difference between
      two groups (P < 0.05 ). (3) The effects of SRC silencing on steroid hormones
      induced SDF-1alpha expression in ectopic endometrium stromal cells: the
      expression of 17beta-estradiol-induced SDF-1alpha at 72 hours was significantly
      decreased from (2 313 +/- 357) ng/L to (1 155 +/- 244) ng/L after the silencing
      of SRC-1 (P < 0.05). After the silencing of SRC-2, the 17beta-estradiol-induced
      SDF-1alpha at 72 hours was (1 958 +/- 324) ng/L. There was no significant
      difference compared with the before the silencing (P > 0.05). The expression of
      SDF-1alpha at 72 hours induced by 17beta-estradiol+progesterone was (1 534 +/-
      449) ng/L and (2 051 +/- 380) ng/L respectively before and after the silencing of
      SRC-2 and showed the significant difference (P < 0.05). CONCLUSION: During the
      expression of SDF-1alpha regulated by steroids in ectopic endometrium cells, SRC
      1 is the major coactivator of 17beta-estradiol and SRC-2 is the major coactivator
      of progesterone.

PMID- 24739644
TI  - [Expression of nerve growth factor produced by ectopic endometrium from patients
      with adenomyosis and its relationship with pain scales and innervation].
AB  - OBJECTIVE: To investigate the expression of nerve growth factor (NGF) in the
      ectopic endometrium in adenomyosis patients, and explore the relationship between
      NGF expression and innervation or pain scales. METHODS: From Mar. 2009 to Oct.
      2009, 45 adenomyosis patients undergoing hysterectomy in Obstetrics and
      Gynecology Hospital of Fudan University were enrolled in this study, which were
      classified into 33 cases in pain group and 12 cases in non-pain group based on
      symptom. The degree of dysmenoreal, chronic pelvic pain and dyspareunia was
      evaluated by visual analogue scale, including no pain, mild to moderate pain and
      severe pain group. In the mean time, 26 patients with leiomyoma or cervical
      intraepithelial neoplasia III (CIN III) undergoing hysterectomy were defined as
      control group. Ectopic endometrium from experimental group and eutopic
      endometrium from control group were collected in the surgery. The expression of
      NGF was examined by immunohistochemistry. The density of protein gene product
      (PGP) 9.5 positive nerve fibers was detected by immuno-fluorescence. RESULTS: The
      NGF level and the density of PGP 9.5 positive nerve fibers in adenomyosis pain
      group (0.25 +/- 0.08, 16 +/- 8 )were higher than adenomyosis painless (0.19 +/-
      0.05, P = 0.007;11 +/- 5, P = 0.018) and control group (0.18 +/- 0.05, P = 0.000;
      9 +/- 4, P = 0.000) . The NGF level and the density of PGP9.5 positive nerve
      fibers in severe dysmenorrheal group (0.29 +/- 0.07, 19 +/- 10) were higher than
      mild to moderate dysmenorrheal (0.22 +/- 0.07, P = 0.018;13 +/- 4, P = 0.035) and
      painless group (0.18 +/- 0.05, P = 0.000;11 +/- 5, P = 0.006) of adenomyosis
      patients. There was no difference of NGF level and the density of PGP 9.5
      positive nerve fibers in chronic pelvic pain group and no chronic pelvic pain
      group of adenomyosis patients, so was dyspareunia group and no dyspareunia group.
      CONCLUSION: The increased NGF level of adenomyosis nodules and improving
      innervation might be involved in the mechanism of adenomyosis related pain.

PMID- 24739645
TI  - [Expression of tight junction factors in human placental tissues derived from
      assisted reproductive technology and natural pregnancy].
AB  - OBJECTIVE: To study the expression of tight junction factors in human placental
      tissues derived from assisted reproductive technology (ART) and natural pregnancy
      and its role in placental barrier. METHODS: Ten placental samples were collected
      from the women who had undergone ART treatment and 11 placenta were collected
      from control group. Transmission electron microscope (TEM) examination was
      utilized to detect the morphology of placental tight junctions. The mRNA of
      claudin (CLDN) 1, CLDN4, CLDN5, CLDN8, zonula occudens (ZO) 1 was detected by
      real-time PCR and the protein of CLDN4, CLDN8 and occludin (OCLN) were measured
      by western blot. RESULTS: TEM microscopy results showed that placenta samples
      derived both ART and control placenta had normal microscopic histological
      features of tight junctions, localized in the apical part of the syncytium and
      also between the cell-cell contacts of fetal blood vessel endothelial. The
      expression level of CLDN4 mRNA were 0.87 +/- 0.17 in ART group and 1.18 +/- 0.30
      in control group, respectively. The expression level of CLDN8 mRNA were 3.25 +/-
      2.32 in ART group and 1.08 +/- 0.41 in control group, respectively. The mRNA
      level of CLDN4 and CLDN8 were significantly differentially expressed in ART
      derived placenta when compared with control groups. The expression level of
      CLDN1, CLDN5, OCLN and ZO1 mRNA were 0.49 +/- 0.44, 0.80 +/- 0.20, 0.92 +/- 0.18
      in ART group and 1.09 +/- 0.82, 1.21 +/- 0.78, 0.80 +/- 0.27 in control group,
      respectively, in which there were no significant differences between two groups.
      Western Blot analysis showed the protein levels of tight junctions CLDN4, CLDN8
      and OCLN did not differ between groups. CONCLUSIONS: Tight junction factors were
      expressed in human placental tissues. Tight junction derived from ATR platenta
      might have mild dysfunction.

PMID- 24739646
TI  - [Expression and regulatory mechanism of microRNA-155 in the villi of patients
      with unexplained recurrent spontaneous abortion patients].
AB  - OBJECTIVE: To study the expression and the mechanism of miR-155in the villi of
      patients with unexplained recurrent spontaneous abortion (URSA). METHODS: The
      expression of miR-155 in the villi of 36 cases with URSA (URSA group) and 25
      women with normal early pregnancy (control group) were detected by stem-loop real
      time reverse transcription (RT) qPCR.Expression of hypoxia inducible factor-1
      (HIF-1alpha), vascular endothelial cell growth factor (VEGF) and micro lymphatic
      vessel density (MVD) in the villi of were measured by immnohistochemical staining
      among two groups. RESULTS: (1)miR-155 expression:the mean miR-155 expression were
      1.456 (0.489, 2.459) in URSA group and 2.833 (1.740, 3.794) in control group,
      which reached statistical difference (P < 0.05). The mean expression of miR-155
      of 1.683 (0.902, 2.459) in URSA group with abortion times ( <= 3) was
      significantly higher than 1.229 (0.489, 1.719) in URSA group with more than 4
      times abortion (P < 0.05). (2) Indexes :the expression of HIF-1alpha, VEGF and
      MVD value were 121 +/- 12, 134 +/- 12, 36 +/- 6 in URSA group and 99 +/- 10, 109
      +/- 10, 28 +/- 4 in control group, which reached statistical difference (P <
      0.01). The expression of HIF-1alpha, VEGF and MVD value of 119 +/- 12, 134 +/-
      12, 35 +/- 5 in URSA group with less than 3 times abortion was significantly
      lower than 128 +/- 12, 138 +/- 12, 43 +/- 6 in URSA group with more than 4 times
      abortion (P < 0.01). CONCLUSIONS: The expression of miR-155 and HIF-1alpha is
      topically stimulated by oxygen signal.HIF-1alpha adjusts the transcription and
      translation of VEGF, which together involved in placental trophoblast invasion
      and placental angiogenesis. The low expression of miR-155 could interfere with
      expression of HIF-1alpha and VEGF, which might be involved in villous vascular
      dysplasia in URSA.

PMID- 24739649
TI  - Congenital disorders of glycosylation with neonatal presentation.
AB  - Congenital disorders of glycosylation (CDG) are a group of hereditary diseases
      characterised by deficiency of enzymes involved in proteins glycosylation. We
      describe the clinical case of a neonate with CDG type 1a, nowadays designated
      phosphomannomutase 2 (PMM2)-CDG. Physical examination showed an abnormal facies,
      axial hypotonia, abnormal fat distribution, inverted nipples, non-palpable
      testicles and arachnodactyly. Progressive multiple system organ involvement and
      worsening of hypertrophic cardiomyopathy occurred. Metabolic study revealed a CDG
      disturbance, which was confirmed by genetic study. The following mutations were
      identified: c.193G>T; p.D65Y and c.470T>C; p.F157S. Clinical deterioration was
      inevitable with multisystemic failure and death. CDG represents a challenge for
      physicians due to multiple organ involvement, and heterogeneous clinical
      manifestations. The neonatal form is usually associated with the worst prognosis.

PMID- 24739648
TI  - The I-TevI nuclease and linker domains contribute to the specificity of monomeric
      TALENs.
AB  - Precise genome editing in complex genomes is enabled by engineered nucleases that
      can be programmed to cleave in a site-specific manner. Here, we fused the small,
      sequence-tolerant monomeric nuclease domain from the homing endonuclease I-TevI
      to transcription-like activator effectors (TALEs) to create monomeric Tev-TALE
      nucleases (Tev-mTALENs). Using the PthXo1 TALE scaffold to optimize the Tev
      mTALEN architecture, we found that choice of the N-terminal fusion point on the
      TALE greatly influenced activity in yeast-based assays, and that the length of
      the linker used affected the optimal spacing of the TALE binding site from the I
      TevI cleavage site, specified by the motif 5'-CNNNG-3'. By assaying activity on
      all 64 possible sequence variants of this motif, we discovered that in the Tev
      mTALEN context, I-TevI prefers A/T-rich triplets over G/C-rich ones at the
      cleavage site. Profiling of nucleotide requirements in the DNA spacer that
      separates the CNNNG motif from the TALE binding site revealed substantial, but
      not complete, tolerance to sequence variation. Tev-mTALENs showed robust
      mutagenic activity on an episomal target in HEK 293T cells consistent with
      specific cleavage followed by nonhomologous end-joining repair. Our data
      substantiate the applicability of Tev-mTALENs as genome-editing tools but
      highlight DNA spacer and cleavage site nucleotide preferences that, while
      enhancing specificity, do confer moderate targeting constraints.

PMID- 24739647
TI  - A nutritional conditional lethal mutant due to pyridoxine 5'-phosphate oxidase
      deficiency in Drosophila melanogaster.
AB  - The concept of auxotrophic complementation has been proposed as an approach to
      identify genes in essential metabolic pathways in Drosophila melanogaster.
      However, it has achieved limited success to date, possibly due to the low
      probability of finding mutations fit with the chemically defined profile. Instead
      of using the chemically defined culture media lacking specific nutrients, we used
      bare minimum culture medium, i.e., 4% sucrose, for adult Drosophila. We
      identified a nutritional conditional lethal mutant and localized a c.95C > A
      mutation in the Drosophila pyridoxine 5'-phosphate oxidase gene [dPNPO or
      sugarlethal (sgll)] using meiotic recombination mapping, deficiency mapping, and
      whole genome sequencing. PNPO converts dietary vitamin B6 such as pyridoxine to
      its active form pyridoxal 5'-phosphate (PLP). The missense mutation (sgll(95))
      results in the substitution of alanine to aspartate (p.Ala32Asp). The sgll(95)
      flies survive well on complete medium but all die within 6 d on 4% sucrose only
      diet, which can be rescued by pyridoxine or PLP supplement, suggesting that the
      mutation does not cause the complete loss of PNPO activity. The sgll knockdown
      further confirms its function as the Drosophila PNPO. Because better tools for
      positional cloning and cheaper whole genome sequencing have made the
      identification of point mutations much easier than before, alleviating the
      necessity to pinpoint specific metabolic pathways before gene identification, we
      propose that nutritional conditional screens based on bare minimum growth media
      like ours represent promising approaches for discovering important genes and
      mutations in metabolic pathways, thereby accelerating the establishment of in
      vivo models that recapitulate human metabolic diseases.

PMID- 24739650
TI  - Delayed rupture of flexor tendons in zone V complicated by neuritis 18 years
      following Galeazzi fracture-dislocation.
AB  - We report a rare case of an 84-year-old woman who presented with delayed,
      complete rupture of superficial (flexor digitorum superficialis) and deep flexor
      tendons (flexor digitorum profundus) of the third, fourth and fifth digits of the
      right hand in zone V of the flexor tendons. The patient, who was otherwise
      healthy, active and independent, incurred a closed fracture of her right wrist 18
      years ago, which was treated conservatively. Current X-rays and operative
      findings confirmed a malunited Galeazzi fracture-dislocation with volar
      dislocation of the ulna from the distal radioulnar joint. She underwent surgical
      treatment to improve her hand function and agonising neuritis symptoms, as she
      was unable to use her middle, ring and little fingers and had developed severe
      neuritis of the ulnar nerve. Exploration and repair of the flexor tendons, nerve
      decompressions and Darrach procedure were performed. On follow-up, the patient
      showed improvement in hand function with the neuritis completely resolved. 

PMID- 24739651
TI  - Aspergilloma and massive haemoptysis.
AB  - A 40-year-old homeless woman who was a known intravenous drug user and heroin
      smoker, presented with massive haemoptysis. Initial CT-pulmonary angiogram (CT
      PA) did not show active haemorrhage but found an opacity in a right upper lobe
      cavity likely to represent a mycetoma. She was started on antifungal therapy but
      haemoptysis persisted and bronchial angiography was performed. Again no active
      haemorrhage was identified but abnormal vasculature was seen supplying the right
      upper lobe. This was empirically embolised with particles which did not improve
      her symptoms. A subsequent CT-PA identified a pulmonary artery pseudoaneurysm in
      the cavity wall which was successfully embolised. There was no further
      haemoptysis and a repeat CT-PA 3 weeks later showed continuing occlusion of the
      pulmonary artery aneurysm. Investigations for tuberculosis were negative and she
      was discharged clinically well and on long-term antifungal therapy. 

PMID- 24739652
TI  - Diagnosis of intestinal ascariasis in modern era.

PMID- 24739653
TI  - Surgical repair following trauma to vascular graft causing spinal cord
      infarction.
AB  - A 55-year-old woman with a background of vascular disease presented with signs of
      bilateral limb ischaemia. Following elective axillobifemoral bypass and hospital
      discharge, accidental axillary trauma causing a chest wall haematoma, the patient
      underwent an emergency graft repair. Postextubation, she reported with absent
      sensation in her legs. Spinal cord infarction was diagnosed through clinical
      assessment and exclusion of other causes. The aetiology of compromise to the
      spinal cord blood supply is unclear. Possibilities include intraoperative
      hypotension, inadvertent compromise to blood supply of thoracic radicular
      arteries, dislodged atherosclerotic emboli or a combination of these factors.
      Spinal cord infarction recognised early can be treated. Sedation to assist
      ventilation had obscured the problem early enough to consider treatment. Patients
      with vascular risk factors should be carefully managed intraoperatively to
      minimise hypotensive episodes and care should also be taken not to compromise
      blood flow of radicular arteries. 

PMID- 24739654
TI  - Haemoptysis in an intravenous drug user: injection needle impacted in the left
      main bronchus.
AB  - We report a case of a 35-year-old man who presented with 4-week history of
      haemoptysis, with a history of intravenous drug use. There was no other
      significant medical or surgical history and no recollection of any foreign body
      aspiration. Chest X-ray and CT scan showed 40 mm long needle in left main
      bronchus, partly lying outside the bronchus into the mediastinum. Flexible and
      rigid bronchoscopes proved to be unsuccessful in retrieving the needle. We
      proceeded with left posterolateral thoracotomy and the left main bronchus was
      explored to take out this 21-gauge (green) injection needle. The distal half of
      the needle with the sharp end was lying in the mediastinum piercing through the
      bronchial wall. Surgery was uneventful with good postoperative recovery and the
      patient was discharged 4 days later. 

PMID- 24739655
TI  - Primary central nervous system lymphoma presenting as choreoathetosis.

PMID- 24739656
TI  - Acute acalculous cholecystitis after abdominal wall repair (Rives-Stoppa).
AB  - Acute acalculous cholecystitis (AAC) is a rare condition normally occurring in
      critically ill patients. Compared to acute calculous cholecystitis, AAC is
      associated with complications and has a worse outcome. Hence, knowledge of this
      condition is very important. We describe a case of a 31-year-old man who
      developed AAC after abdominal wall repair with mesh (Rives-Stoppa procedure) 1
      day after discharge from the hospital. To the best of our knowledge, this is the
      first paper to report AAC after abdominal incisional hernia repair. Although it
      is known to be more common in critically ill patients, AAC can also occur
      postoperatively in outpatients. Early recognition and treatment of AAC may
      improve outcome. 

PMID- 24739657
TI  - Submucosal uterine fibroid prolapsed into vagina in a symptomatic patient with
      IUS.
AB  - A female patient in her mid 40s presents with heavy menstrual bleeding (HMB) and
      a history of spotting/irregular light per vagina (PV) bleeding since intrauterine
      system (IUS) insertion 1 year ago. She is known to have submucosal uterine
      fibroid (SMUF). The patient reported abdominal pain and sudden onset of
      'miscarriage-like' HMB with clots 2 days ago. On speculum examination there was a
      smooth round-shaped mass lying over the external cervical os. On bimanual
      examination PV, a round-shaped smooth mass of a walnut's size was palpable in the
      upper third of the vagina. Subsequent ultrasound imaging revealed an SMUF
      prolapsed into the vagina. Further surgical treatment was undertaken. Histology
      showed a fibroid (leiomyoma) with no evidence of malignancy. 

PMID- 24739658
TI  - Protein synthesis and secretion in human mesenchymal cells derived from bone
      marrow, adipose tissue and Wharton's jelly.
AB  - INTRODUCTION: Different mesenchymal stromal cells (MSC) have been successfully
      isolated and expanded in vitro and nowadays they are tested in clinical trials
      for a wide variety of diseases. Whether all MSC express the same cell surface
      markers or have a similar secretion profile is still controversial, making it
      difficult to decide which stromal cell may be better for a particular
      application. METHODS: We isolated human mesenchymal stromal cells from bone
      marrow (BM), adipose tissue (AT) and Wharton's jelly (WJ) and cultured them in
      fetal bovine serum supplemented media. We evaluated proliferation, in vitro
      differentiation (osteogenic, adipogenic and chondrogenic potential), expression
      of cell surface markers and protein secretion using Luminex and ELISA assays.
      RESULTS: Cell proliferation was higher for WJ-MSC, followed by AT-MSC.
      Differences in surface expression markers were observed only for CD54 and CD146.
      WJ-MSC secreted higher concentrations of chemokines, pro-inflammatory proteins
      and growth factors. AT-MSC showed a better pro-angiogenic profile and secreted
      higher amounts of extracellular matrix components and metalloproteinases.
      CONCLUSIONS: Mesenchymal stromal cells purified from different tissues have
      different angiogenic, inflammatory and matrix remodeling potential properties.
      These abilities should be further characterized in order to choose the best
      protocols for their therapeutic use.

PMID- 24739659
TI  - Effectiveness of three treatment strategies on occupational limitations and
      quality of life for patients with non-specific chronic low back pain: Is a
      multidisciplinary approach the key feature to success: study protocol for a
      randomized controlled trial.
AB  - BACKGROUND: Chronic low back pain (cLBP) is a significant public health problem,
      being the primary cause of work absenteeism, as well as affecting sufferers'
      quality of life, in industrialized society. International guidelines recommend
      intensive multidisciplinary approaches for patients with cLBP. However, these
      costly and time-consuming programs can only be offered to a minority of the most
      heavily affected patients and therefore do not seem likely to respond to public
      health requirements. Lighter programs may be an alternative to full time hospital
      based programs with valuable results in terms of disability and occupational
      activity for cLBP patients. It is therefore important to define both what the
      determining components of management to improve activity restriction are and how
      to treat a larger number of patients more effectively at a lower cost. The aim of
      this study is to compare three programs with various levels of intensity and
      multidisciplinary. METHODS/DESIGN: This paper describes the protocol for a
      prospective, randomized, controlled, clinical trial in working aged patients with
      cLBP. Three treatment strategies are compared: (1) intensive and
      multidisciplinary program conducted in a rehabilitation center; (2) less
      intensive outpatient program conducted by a private physiotherapist; (3) mixed
      strategy combining the same out program with a multidisciplinary intervention.
      The primary outcome of the trial is the impact of the mixed strategy on being
      able to work compared to hospital centered-program and out program. The secondary
      outcome is the impact of the mixed strategy on quality of life and social ability
      compared to the two others programs. The intervention part of the trial programs
      will take 5 weeks and observational follow-up will take 12 months. The sample
      size will be 180 participants (60 for each arm). The project has been approved by
      the Ethical Committee of Angers Hospital, France. DISCUSSION: On the hypothesis
      that a multidisciplinary approach is the key feature to programs success in
      reducing social and occupational impairment in cLBP patients, we suggest that it
      is possible to achieve the same results with less intensive strategies if a
      multidisciplinary approach is maintained. TRIAL REGISTRATION: Current Controlled
      Trials NCT02030171.

PMID- 24739660
TI  - Depressive symptoms and social support among people living with HIV in Hunan,
      China.
AB  - Depressive symptoms are common among people living with HIV (PLWH) and are
      associated with poor adherence to antiretroviral treatment and poor treatment
      outcomes. Our study investigated the prevalence of and factors associated with
      depressive symptoms in PLWH in one Chinese province. Data were collected from 496
      PLWH between July 2009 and July 2010 at two HIV treatment sites in Hunan
      Province, China. Sixty-two percent (n = 309) of participants scored 16 or more on
      the Center for Epidemiological Studies of Depression scale, indicating moderate
      to high levels of depressive symptoms. Independent predictors of depressive
      symptoms included active heroin use, lack of a stable job, female gender, and
      limited social support. These data suggest that interventions addressing
      depressive symptoms should be included in HIV care programs provided by the
      Chinese government, with a special focus on PLWH who are heroin users, female,
      unemployed, or socially isolated. 

PMID- 24739661
TI  - A survey of nurse-initiated and -managed antiretroviral therapy (NIMART) in
      practice, education, policy, and regulation in east, central, and southern
      Africa.
AB  - In sub-Saharan Africa, nurses and midwives perform many HIV service delivery
      tasks, such as diagnosis of HIV and prescription of antiretroviral therapy (ART),
      which used to be the responsibility of physicians. While this task shifting is
      critical to scaling-up HIV services in Africa, the extent of HIV task shifting is
      not well understood. A survey of senior nursing leadership teams from 15 African
      countries was carried out to describe the extent of nurse-initiated and -managed
      antiretroviral therapy (NIMART) in practice, education, policy, and regulation.
      The survey took place at the African Health Professions Regulatory Collaborative
      meeting in Pretoria, South Africa, in June 2012. The findings indicated that
      NIMART is widely practiced and authorized in policy, but is not reinforced by
      regulation nor incorporated into preservice education. Further investment in
      policy, regulation, and pre-service education is needed to ensure sustainable,
      high quality ART service expansion through the region. 

PMID- 24739662
TI  - Exploring the usability of a videophone mock-up for persons with dementia and
      their significant others.
AB  - BACKGROUND: Persons with dementia might have considerable difficulties in using
      an ordinary telephone. Being able to use the telephone can be very important in
      order to maintain their social network, getting stimulation and for reaching help
      when needed. Therefore, persons with dementia might need an easy-to-use
      videophone to prevent social isolation and to feel safe and independent. This
      study reports the evaluation of the usability of a touch-screen videophone mock
      up for persons with dementia and their significant others. METHODS: Four persons
      with dementia and their significant others tested the videophone mock-up at a
      living laboratory. In order to gain knowledge of the participants' with dementia
      ability to use their own computers and telephones, interviews and observations
      were conducted. RESULTS: Overall, the participants had a very positive attitude
      towards the videophone. The participants with dementia perceived that it was
      useful, enjoyable and easy to use, although they initially had difficulties in
      understanding how to handle some functions, thus indicating that the design needs
      to be further developed to be more intuitive. CONCLUSIONS: The findings suggest
      that the videophone has the potential to enable telephone calls without
      assistance and add quality in communication.

PMID- 24739663
TI  - Effects of unbound mycophenolic acid on inosine monophosphate dehydrogenase
      inhibition in pediatric kidney transplant patients.
AB  - BACKGROUND: Mycophenolic acid (MPA) is a key immunosuppressive drug that acts
      through inhibition of inosine monophosphate dehydrogenase (IMPDH). MPA is
      commonly measured, as part of therapeutic drug monitoring, as the total
      concentration in plasma. However, it has been postulated that the free (unbound)
      fraction of MPA (fMPA) is responsible for the immunosuppressive effects. In this
      study, a sensitive low volume high-performance liquid chromatography (HPLC) assay
      was developed to measure fMPA concentrations to explore the relationship between
      fMPA and IMPDH activity. METHODS: To obtain fMPA concentrations, plasma samples
      were filtrated using Centrifree ultrafiltration devices. The ultrafiltrate was
      analyzed by HPLC using a Kinetex C18 column (2.6 MUm, 3.0 * 75 mm). fMPA
      concentrations were compared with the total MPA concentrations available in 28
      pediatric kidney transplant patients at 3 consecutive occasions after
      transplantation. The relationship between fMPA and IMPDH activity was analyzed
      using an Emax model. RESULTS: The HPLC assay, using 25 MUL of the ultrafiltrates,
      was validated over a range from 2.5 to 1000 MUL with good accuracy, precision,
      and reproducibility. Total and free MPA concentrations were well correlated (R =
      0.85, P < 0.0001), although large intraindividual and interindividual variability
      in the bound MPA fractions was observed. The overall relationship between fMPA
      concentrations and IMPDH inhibition using the Emax model was comparable with that
      of total MPA, as previously reported. The model estimated EC50 value (164.5 MUL)
      is in good agreement with reported in vitro EC50 values. CONCLUSIONS: This study
      provides a simple HPLC method for the measurement of fMPA and a pharmacologically
      reasonable EC50 estimate. The good correlation between the total and free MPA
      concentrations suggests that routine measurement of fMPA to characterize
      mycophenolate pharmacokinetic and pharmacodynamic does not seem warranted,
      although the large variability in the bound fractions of MPA warrants further
      study.

PMID- 24739664
TI  - Population pharmacokinetic analysis of diurnal and seasonal variations of plasma
      concentrations of cilostazol in healthy volunteers.
AB  - BACKGROUND: The background of this study was (1) to examine factors influencing
      cilostazol pharmacokinetics by developing a population model incorporating
      diurnal variation and other covariate effects and (2) to assess the feasibility
      of applying the developed model to determine the optimal dosing times. METHODS:
      Data obtained from a cilostazol pharmacokinetic study consisting of 2 clinical
      trials (a single twice-a-day (BID) dosing trial in winter and a multiple BID
      dosing trial in summer) conducted in healthy Korean subjects were used for model
      building. A basic model was built, followed by a diurnal variation model, and
      then a final model was built incorporating covariates, including a seasonal
      difference. The optimal morning and evening dosing times were determined from
      simulations. RESULTS: Diurnal variation in cilostazol pharmacokinetics was
      explained by the morning absorption rate constant being faster than in the
      evening, yielding values of 0.278 versus 0.234/h in summer, when 24- and 12-hour
      circadian rhythms were included in the model. The seasonal variation was
      explained by a 26.9% and a 31.8% decrease in the absorption rate constant and
      clearance, respectively, in winter compared with summer. Based on twice-a-day
      (BID) dosing, dosing times of 9 AM and 5 PM in summer and 10 AM and 7 PM in
      winter were expected to produce the smallest peak-to-peak fluctuations in
      cilostazol concentration, possibly minimizing unwanted effects of the drug.
      CONCLUSIONS: This study demonstrated the intraday and interseasonal time-varying
      nature of cilostazol pharmacokinetics using a population modeling approach and
      developed a strategy for optimizing dosing times. It is suggested that these
      methods can be similarly applied to analyses and controls of other drugs that
      exhibit characteristics of time-varying pharmacokinetics.

PMID- 24739665
TI  - Pharmacokinetic drug interaction between cyclosporine and imatinib in bone marrow
      transplant children and model-based reappraisal of imatinib drug interaction
      profile.
AB  - BACKGROUND: Previous reports have suggested that imatinib may increase
      cyclosporine exposure by CYP3A4 inhibition. However, the magnitude of this drug
      interaction remains unclear. At present, quantitative information about the
      interaction profile of imatinib is scarce. METHODS: The authors report the effect
      of imatinib on cyclosporine exposure in 6 pediatric patients with Philadelphia
      chromosome-positive acute lymphoblastic leukemia who received cyclosporine after
      hematopoietic stem-cell transplantation. Dose-normalized cyclosporine trough
      blood concentrations (TBC) were obtained before and after imatinib introduction.
      In addition, a validated model-based approach was used to derive quantitative
      predictions of CYP3A4-mediated drug interactions with imatinib as a victim or
      precipitant drug. RESULTS: The mean dose-normalized cyclosporine TBC
      significantly increased after 3 to 7 days of imatinib therapy. The modeling
      approach predicted weak-to-moderate effect of major CYP3A4 inhibitors on imatinib
      exposure. However, the inhibitory potency of imatinib was found to be similar to
      that of verapamil, suggesting significant influence of imatinib on the
      pharmacokinetics of drugs highly metabolized by CYP3A4. Observed increases in
      cyclosporine dose-normalized TBC of the 6 patients were compatible with model
      predictions. The observations and predictions suggest that imatinib may
      substantially increase cyclosporine exposure. CONCLUSIONS: Cyclosporine dose
      reduction may be necessary to avoid excessive immunosuppressive effect in case of
      coadministration of imatinib.

PMID- 24739666
TI  - Lights and shadows of the actual European guidelines on bioanalytical method
      validation: the case of raltegravir.
AB  - BACKGROUND: Recently, the European Medicines Agency (EMA) has released new
      guidelines on the validation of bioanalytical methods. In this work, we compared
      the analytical performance of 2 high-performance liquid chromatography with
      tandem mass spectrometry methods designed for the quantification of the
      antiretroviral drug raltegravir (RAL) that fully accomplish the criteria
      according to the new EMA guidelines. METHODS: The first method was developed with
      the goal of separating RAL from its main metabolite, whereas in the second
      method, we deliberately did not discriminate the parent drug from its metabolite.
      After validation, both methods were used for the quantification of plasma samples
      from HIV-infected patients on RAL-based maintenance antiretroviral therapy.
      RESULTS: Incurred reanalysis of samples obtained from patients receiving RAL as
      therapy evidenced optimal performance for both methods. Similarly, the comparison
      of both methods performed by the Deming test showed that they correlate
      significantly with each other (Pearson coefficient of regression 0.97, P <
      0.0001) with no significant deviation from linearity according to the Cusum test.
      The Bland-Altman test, however, showed a mean difference between the 2 methods of
      54.1% (limits of agreements of +/-1.96 SD ranged from -163.3% to +271.5%). Such
      differences were significantly affected by interindividual variations in the
      production of RAL metabolites. CONCLUSIONS: We conclude that the recently
      released EMA guidelines on bioanalytical method validation present some
      limitations related to the process of method development. To have confidence in
      the drug-concentration measurements, laboratories must demonstrate their
      performance through the participation in international proficiency testing
      schemes that must include patient samples.

PMID- 24739667
TI  - Using fluorescence polarization immunoassay for determination of erythrocyte
      methotrexate polyglutamates, a quick and easy test?
AB  - BACKGROUND: The folate antagonist methotrexate (MTX) is the anchor drug in the
      treatment of rheumatoid arthritis. The therapeutic effects of MTX are attributed
      to the intracellular levels of MTX, present in the cell as polyglutamates (MTX
      PGs). We aimed to validate an immunoassay for the measurement of MTX-PG in
      erythrocytes. METHODS: Samples were analyzed by an adapted fluorescence
      polarization immune assay (FPIA) method on the FLx analyzer (Abbott). Cross
      reactivity was determined in both plasma and erythrocyte pellet. In erythrocyte
      pellet, the imprecision, linearity, and lower limit of quantitation were
      determined. The method was compared with our in-house liquid chromatography
      tandem mass spectrometry (LC-MS/MS) method for total MTX-PG. RESULTS: For the
      adapted FPIA method, a linear range of 25-1000 nmol/L (R = 0.993) was obtained
      for total MTX-PG in erythrocytes. A coefficient of variation of <17% for interday
      and <8% for intraday imprecision was found and average recovery was 91%. Lower
      limit of quantitation was determined at 50 nmol/L total MTX-PG with a coefficient
      of variation of 15%. There was no significant proportional bias of the FPIA assay
      compared with our in-house LC-MS/MS method, but a (nonsignificant) constant
      positive bias was present [FPIA = 1.00 (95% confidence interval: 0.60-1.95) * LC
      MS/MS + 31.00 nmol/L (95% confidence interval: -11.83 to 61.00)]. Results could
      be very different for individual patients as reflected in the poor R of 0.419.
      CONCLUSIONS: The FPIA method can be used to measure total MTX-PG in erythrocytes.
      Although there was no significant bias detected compared with the LC-MS/MS
      method, the FPIA method showed constant positive bias, probably because of
      interference from folates and MTX metabolites 2,4-diamino-N10-methylpteroic acid
      and 7-hydroxy-MTX. The correlation between both methods was average and resulted
      in large differences in individual patients, most likely because of problems
      during sample preparation.

PMID- 24739668
TI  - Lack of correlation between the steady-state plasma concentrations of
      aripiprazole and haloperidol in Japanese patients with schizophrenia.
AB  - BACKGROUND: Both aripiprazole and haloperidol have been used in the treatment of
      schizophrenia, and are metabolized by the cytochrome P450 (CYP) 2D6 and CYP3A4.
      The authors studied the correlations between the steady-state plasma
      concentrations (Css) of aripiprazole and its active metabolite,
      dehydroaripiprazole, and those of haloperidol in 19 Japanese patients with
      schizophrenia, together with the effects of CYP2D6 genotypes on the steady-state
      kinetics of these compounds. METHODS: All the patients received first 24 mg/d of
      aripiprazole for 3 weeks and later received 6 mg/d of haloperidol for 2 weeks.
      Blood samplings were performed at least 2 weeks after the initiation of each
      treatment. The Css values of aripiprazole and dehydroaripiprazole were measured
      using liquid chromatography with mass spectrometric detection, and those of
      haloperidol were measured by using an enzyme immunoassay. CYP2D6 genotypes were
      determined by using polymerase chain reaction analysis. RESULTS: None of the
      correlations between the Css of aripiprazole (r = 0.286) or the sum of
      aripiprazole plus dehydroaripiprazole (r = 0.344) and those of haloperidol were
      significant. The mean Css of aripiprazole was significantly higher (P < 0.05) in
      the subjects with 1 *10 allele of CYP2D6 (n = 6) than in those with no mutated
      alleles (n = 13), whereas there were no significant differences in those of
      haloperidol between the 2 groups. CONCLUSIONS: This study suggests that the Css
      of aripiprazole and that of aripiprazole plus dehydroaripiprazole do not
      correlate with that of haloperidol in the same individual, because of the greater
      involvement of CYP2D6 in the metabolism of aripiprazole than in that of
      haloperidol.

PMID- 24739669
TI  - CYP3A5*3 and POR*28 genetic variants influence the required dose of tacrolimus in
      heart transplant recipients.
AB  - BACKGROUND: After heart transplantation (HTx), the interindividual
      pharmacokinetic variability of immunosuppressive drugs represents a major
      therapeutic challenge due to the narrow therapeutic window between over
      immunosuppression causing toxicity and under-immunosuppression leading to graft
      rejection. Although genetic polymorphisms have been shown to influence
      pharmacokinetics of immunosuppressants, data in the context of HTx are scarce. We
      thus assessed the role of genetic variation in CYP3A4, CYP3A5, POR, NR1I2, and
      ABCB1 acting jointly in immunosuppressive drug pathways in tacrolimus (TAC) and
      ciclosporin (CSA) dose requirement in HTx recipients. METHODS: Associations
      between 7 functional genetic variants and blood dose-adjusted trough (C0)
      concentrations of TAC and CSA at 1, 3, 6, and 12 months after HTx were evaluated
      in cohorts of 52 and 45 patients, respectively. RESULTS: Compared with CYP3A5
      nonexpressors (*3/*3 genotype), CYP3A5 expressors (*1/*3 or *1/*1 genotype)
      required around 2.2- to 2.6-fold higher daily TAC doses to reach the targeted C0
      concentration at all studied time points (P <= 0.003). Additionally, the POR*28
      variant carriers showed higher dose-adjusted TAC-C0 concentrations at all time
      points resulting in significant differences at 3 (P = 0.025) and 6 months (P =
      0.047) after HTx. No significant associations were observed between the genetic
      variants and the CSA dose requirement. CONCLUSIONS: The CYP3A5*3 variant has a
      major influence on the required TAC dose in HTx recipients, whereas the POR*28
      may additionally contribute to the observed variability. These results support
      the importance of genetic markers in TAC dose optimization after HTx.

PMID- 24739670
TI  - Comparison of nanosilver removal by flocculent and granular sludge and short- and
      long-term inhibition impacts.
AB  - The growing production and application of silver nanoparticles (Ag NPs) increases
      the chance of these particles entering wastewater treatment plants and
      interacting with activated sludge. In this paper, the removal of Ag NPs by
      flocculent and granular sludge was studied, and the short- and long-term
      inhibitory impacts of Ag NPs on the sludge were compared. Results showed that
      both forms of sludge contributed to removal of Ag NPs with 30-58% and 2.5-9.4%
      removal by the flocculent sludge and the granular sludge, respectively, at Ag NP
      dosage of 1-8 mg/L. Exposure to Ag NPs had greater inhibitive effects on the
      flocculent sludge than the granular sludge. Short-term (12 h) exposure to Ag NPs
      at 1, 10, 50 and 100 mg/L reduced the ammonia oxidizing rate of the flocculent
      sludge by 21.0-24.9%, while no inhibition was found for the granular sludge; the
      oxygen uptake rate of the flocculent sludge was inhibited at Ag NP concentrations
      as low as 1 mg/L, while that of the granular sludge was only affected at much
      higher Ag NP concentrations (50 and 100 mg/L). The denitrification rate, however,
      was not inhibited for either sludge. After long-term (22 day) exposure to 5 and
      50 mg/L of Ag NPs, flocculent sludge was significantly inhibited on ammonia
      oxidizing rate, denitrification rate and oxygen uptake rate, but the microbial
      activity of granular sludge was not inhibited. Exposure to Ag NPs resulted in
      oxidative stress and damage of bacterial cell integrity for both flocculent and
      granular sludge as was determined by generation of reactive oxygen species and
      release of lactate dehydrogenase (LDH). The toxic effect of Ag NPs on sludge was
      mediated via both ROS-dependent and ROS-independent pathways, and both small (<10
      nm) and large (>10 nm) Ag NPs contributed to it. Overall, granular sludge
      demonstrated stronger resistance to the toxicity of Ag NPs than flocculent
      sludge, while flocculent sludge was more efficient in removing Ag NPs. 

PMID- 24739672
TI  - In this issue of Epigenetics: special focus on non-coding RNAs in epigenetic
      regulation.

PMID- 24739671
TI  - Autoinhibition of the Ron receptor tyrosine kinase by the juxtamembrane domain.
AB  - BACKGROUND: The Ron receptor tyrosine kinase (RTK) has been implicated in the
      progression of a number of carcinomas, thus understanding the regulatory
      mechanisms governing its activity is of potential therapeutic significance. A
      critical role for the juxtamembrane domain in regulating RTK activity is
      emerging, however the mechanism by which this regulation occurs varies
      considerably from receptor to receptor. RESULTS: Unlike other RTKs described to
      date, tyrosines in the juxtamembrane domain of Ron are inconsequential for
      receptor activation. Rather, we have identified an acidic region in the
      juxtamembrane domain of Ron that plays a central role in promoting receptor
      autoinhibition. Furthermore, our studies demonstrate that phosphorylation of
      Y1198 in the kinase domain promotes Ron activation, likely by relieving the
      inhibitory constraints imposed by the juxtamembrane domain. CONCLUSIONS: Taken
      together, our experimental data and molecular modeling provide a better
      understanding of the mechanisms governing Ron activation, which will lay the
      groundwork for the development of novel therapeutic approaches for targeting Ron
      in human malignancies.

PMID- 24739673
TI  - A novel tree-based procedure for deciphering the genomic spectrum of clinical
      disease entities.
AB  - BACKGROUND: Dissecting the genomic spectrum of clinical disease entities is a
      challenging task. Recursive partitioning (or classification trees) methods
      provide powerful tools for exploring complex interplay among genomic factors,
      with respect to a main factor, that can reveal hidden genomic patterns. To take
      confounding variables into account, the partially linear tree-based regression
      (PLTR) model has been recently published. It combines regression models and tree
      based methodology. It is however computationally burdensome and not well suited
      for situations for which a large number of exploratory variables is expected.
      METHODS: We developed a novel procedure that represents an alternative to the
      original PLTR procedure, and considered different selection criteria. A
      simulation study with different scenarios has been performed to compare the
      performances of the proposed procedure to the original PLTR strategy. RESULTS:
      The proposed procedure with a Bayesian Information Criterion (BIC) achieved good
      performances to detect the hidden structure as compared to the original
      procedure. The novel procedure was used for analyzing patterns of copy-number
      alterations in lung adenocarcinomas, with respect to Kirsten Rat Sarcoma Viral
      Oncogene Homolog gene (KRAS) mutation status, while controlling for a cohort
      effect. Results highlight two subgroups of pure or nearly pure wild-type KRAS
      tumors with particular copy-number alteration patterns. CONCLUSIONS: The proposed
      procedure with a BIC criterion represents a powerful and practical alternative to
      the original procedure. Our procedure performs well in a general framework and is
      simple to implement.

PMID- 24739678
TI  - Statistical power and significance testing in large-scale genetic studies.
AB  - Significance testing was developed as an objective method for summarizing
      statistical evidence for a hypothesis. It has been widely adopted in genetic
      studies, including genome-wide association studies and, more recently, exome
      sequencing studies. However, significance testing in both genome-wide and exome
      wide studies must adopt stringent significance thresholds to allow multiple
      testing, and it is useful only when studies have adequate statistical power,
      which depends on the characteristics of the phenotype and the putative genetic
      variant, as well as the study design. Here, we review the principles and
      applications of significance testing and power calculation, including recently
      proposed gene-based tests for rare variants. 

PMID- 24739680
TI  - The crystal orientation relation and macroscopic surface roughness in hetero
      epitaxial graphene grown on Cu/mica.
AB  - Clean, flat and orientation-identified graphene on a substrate is in high demand
      for graphene electronics. In this study, the hetero-epitaxial graphene growth on
      Cu(111)/mica(001) by chemical vapor deposition is investigated to check the
      applicability for top-gate insulator research on graphene, as well as graphene
      channel research, by transferring graphene on to SiO2/Si substrates. After
      adjusting the graphene growth conditions, the surface roughness of the
      graphene/Cu/mica substrate and the average smoothed areas are ~0.34 nm and ~100
      MUm(2), respectively. The orientation of graphene in the graphene/Cu/mica
      substrate can be identified by the hexagonal void morphology of Cu. Moreover, we
      demonstrate a relatively high mobility of ~4500 cm(2) V(-1) s(-1) in graphene
      transferred on the SiO2/Si substrate. These results suggest that the present
      graphene/Cu/mica substrate can be used for top-gate insulator research on
      graphene. 

PMID- 24739679
TI  - Identification of KMT2D and KDM6A mutations by exome sequencing in Korean
      patients with Kabuki syndrome.
AB  - Kabuki syndrome (KS) (OMIM#147920) is a multiple congenital anomaly/mental
      retardation syndrome. Recently, pathogenic variants in KMT2D and KDM6A were
      identified as the causes of KS in 55.8-80.0% of patients. To elucidate further
      the molecular characteristics of Korean patients with KS, we screened a cohort of
      patients with clinically defined KS for mutations in KMT2D and KDM6A. Whole-exome
      sequencing and direct sequencing for validation were performed in 12 patients
      with a clinical suspicion of KS. KMT2D and KDM6A mutations were identified in 11
      (91.7%) patients. No recurrent mutation was observed, and 10 out of the 11
      mutations found were novel. KMT2D mutations were detected in 10 patients,
      including four small deletions or insertions and four nonsense and two missense
      mutations. One girl had a novel splice-site mutation in KDM6A. Each patient had a
      unique individual mutation. This is the first report of mutational analysis via
      exome sequencing in Korean patients with KS. Because the mutation-detection rate
      was high in this study, rigorous mutation analysis of KMT2D and KDM6A may be an
      important tool for the early diagnosis and genetic counseling of Korean patients
      with KS. 

PMID- 24739682
TI  - Pneumatic stenting for tracheobronchomalacia.

PMID- 24739681
TI  - Effect of bovine adenovirus 3 on mitochondria.
AB  - Viruses alter the structure and the function of mitochondria for survival.
      Electron microscopy analysis of the cells infected with bovine adenovirus 3
      revealed extensive damage to the inner mitochondrial membrane characterized by
      dissolution of the cristae and amorphous appearance of mitochondrial matrix with
      little or no damage to the outer mitochondrial membrane. There were fewer cristae
      with altered morphology. Potential patches of protein synthesis machinary around
      mitochondria could be observed at 12 hours post infection (hpi). At 24 hpi, the
      multi vascular bodies were evident throughout the infected cell. ATP production,
      mitochondrial Ca2+ and mitochondrial membrane potential (MMP) peaked at 18 hpi
      but decreased significantly at 24 hpi. This decrease coincided with the increased
      production of superoxide (SO) and reactive oxygen species (ROS), at 24 hpi
      indicating acute oxidative stress in the cells and suggesting a complete failure
      of the cellular homeostatic machinary. The results reveal an intericate
      relationship between Ca2+ homeostasis, the ATP generation ability of cells, SO
      and ROS production, and regulation of MMP following infection by bovine
      adenovirus 3. 

PMID- 24739683
TI  - Virtual Bronchoscopy Using OsiriX.
AB  - BACKGROUND: Although the utility of virtual bronchoscopy has been reported, the
      software for virtual bronchoscopy has not been popular because of the high cost.
      OsiriX is a reasonably priced software that is available to reconstruct virtual
      endoscopic images. Herein, we present the ability of OsiriX to enable virtual
      bronchoscopy. METHODS: Computed tomography of the chest was performed using a 16
      row multidetector. Data in 2 mm slices from one lung were obtained from 10
      patients with a lung nodule. Virtual bronchoscopic images were established by
      OsiriX version 5.5 (32-bit). To examine the ability to visualize small bronchi,
      we tried to visualize the distal bronchus if possible. We selected B and B for
      the right lung and B and B for the left lung. In addition, to predict whether a
      pathologic diagnosis can successfully be made by transbronchial lung biopsy, we
      reconstructed virtual bronchoscopic images toward the lung nodule. RESULTS:
      Bronchoscopic images were successfully reconstructed for all patients. The third
      to the seventh bronchi were visualized except in one patient whose right B was
      occluded by a tumor. In all patients, the virtual bronchoscopic path reached the
      lung nodule, and 5 lung nodules were successfully diagnosed by transbronchial
      biopsy. CONCLUSIONS: OsiriX is practicable for virtual bronchoscopy at a low
      cost.

PMID- 24739684
TI  - Bronchoscopic training and practice in australia and New Zealand is inconsistent
      with published society guidelines.
AB  - BACKGROUND: The Australasian practice and training in bronchoscopy has not
      previously been reported and procedure volumes among Australasian respiratory
      consultants and trainees are unknown. We surveyed the current practice of
      flexible bronchoscopy in Australasia and determined adherence to published
      recommendations. METHODS: Adult physician and trainee members of the Thoracic
      Society of Australia New Zealand (TSANZ) were e-mailed a web-link to an online
      survey. Survey responses were benchmarked against TSANZ recommendations. RESULTS:
      The response rate was 42% overall and 78% among trainees. Forty-nine percent of
      consultants performed less than the recommended 50 procedures per year. Sixty
      percent of trainees were unlikely to achieve the recommended 200 supervised
      bronchoscopies during training. Less than 20% of trainees received adequate
      training in advanced bronchoscopic techniques such as transbronchial lymph node
      aspiration. The majority of physicians performing such advanced techniques were
      not performing sufficient numbers to satisfy published recommendations.
      CONCLUSIONS: A large proportion of Australasian bronchoscopists do not meet
      "numbers-based" recommendations. This empirical data support the 2012 TSANZ
      interventional guidelines' call to move beyond procedural volume as the sole
      determinant of technical competence. There is an urgent need to explore
      alternative means of developing and defining bronchoscopic proficiency.

PMID- 24739685
TI  - Electromagnetic navigational bronchoscopy-guided fiducial markers for lung
      stereotactic body radiation therapy: analysis of safety, feasibility, and
      interfraction stability.
AB  - BACKGROUND: Embolization coils as fiducial markers for pulmonary stereotactic
      body radiation therapy (SBRT) are perceived to be the optimal marker type, given
      their ability to conform and anchor within the small airways. The aim of our
      study was to assess retention, placement, migration, feasibility, and safety of
      electromagnetic navigational bronchoscopy (ENB)-guided embolization coil markers
      throughout courses of SBRT. METHODS: Thirty-one patients with 34 nodules
      underwent ENB-guided fiducial placement of several 4 mm fibered platinum
      embolization coils before SBRT. Patient and nodule positioning was confirmed with
      daily pretreatment cone-beam computed tomography (CBCT). Fiducial positional
      characteristics were analyzed utilizing radiation treatment-planning software
      comparing the simulation CT with daily CBCTs. RESULTS: Of 105 fiducials placed,
      103 were identifiable on simulation CT (retention rate: 98.1%). Incidence of
      asymptomatic pneumothoraces was 6%. One patient experienced hemoptysis requiring
      hospitalization. Eighty-six percent of fiducials were placed within 1 cm of the
      nodule, with 52% of fiducials placed directly on the nodule surface. Throughout a
      5-fraction SBRT course, fiducial displacement was <7, 5, and 2 mm in 98%, 96%,
      and 67% of pretreatment CBCTs. CONCLUSIONS: ENB placement of embolization coils
      as fiducials for lung SBRT image guidance is associated with a low rate of
      iatrogenic pneumothoraces, and resulted in reliable placement of the fiducials in
      close proximity to the lung nodule. Embolization coils retained their relative
      position to the nodule throughout the course of SBRT, and provide an excellent
      alternative to linear gold seeds.

PMID- 24739686
TI  - Value of the polymerase chain reaction method for detecting tuberculosis in the
      bronchial tissue involved by anthracosis.
AB  - BACKGROUND: Anthracofibrosis is the black discoloration of the bronchial mucosa
      with deformity and obstruction. Association of this disease with tuberculosis
      (TB) was approved. The objective of this study was to find the additional benefit
      of assessment of TB by the polymerase chain reaction (PCR) method. METHODS:
      Bronchoscopy was performed on 103 subjects (54 anthracofibrosis and 49 control
      subjects) who required bronchoscopy for their pulmonary problems. According to
      bronchoscopic findings, participants were classified to anthracofibrosis and
      nonanthracotic groups. They were examined for TB with traditional methods such as
      direct smear (Ziehl-Neelsen staining), Lowenstein-Jensen culture, and
      histopathology and the new method "PCR" for Mycobacterium tuberculosis genome
      (IS6110). RESULTS: Age, sex, smoking, and clinical findings were not
      significantly different in the TB and the non-TB groups. Acid-fast bacilli could
      be detected by a direct smear in 12 (25%) of the anthracofibrosis subjects, and
      adding the results of culture and histopathology traditional tests indicated TB
      in 27 (31%) of the cases. Mycobacterium tuberculosis was diagnosed by PCR in 18
      (33%) patients, but the difference was not significant. Detection of acid-fast
      bacilli in control nonanthracosis subjects was significantly lower (3, 6%), but
      PCR (20, 40%) and accumulation of results from all traditional methods (22, 44%)
      showed a nonsignificant difference. CONCLUSIONS: The PCR method showed a result
      equal to traditional methods including accumulation of smear, culture, and
      histopathology.

PMID- 24739687
TI  - Efficiency of performing pulmonary procedures in a shared endoscopy unit:
      procedure time, turnaround time, delays, and procedure waiting time.
AB  - BACKGROUND: The purpose of this study was to assess the efficiency of performing
      pulmonary procedures in the endoscopy unit in a large teaching hospital. METHODS:
      A prospective study from May 20 to July 19, 2013, was designed. The main outcome
      measures were procedure delays and their reasons, duration of procedural steps
      starting from patient's arrival to endoscopy unit, turnaround time, total case
      durations, and procedure wait time. RESULTS: A total of 65 procedures were
      observed. The most common procedure was BAL (61%) followed by TBLB (31%). Overall
      procedures for 35 (53.8%) of 65 patients were delayed by >= 30 minutes, 21/35
      (60%) because of "spillover" of the gastrointestinal and surgical cases into the
      time block of pulmonary procedure. Time elapsed between end of pulmonary
      procedure and start of the next procedure was >= 30 minutes in 8/51 (16%) of
      cases. In 18/51 (35%) patients there was no next case in the room after
      completion of the pulmonary procedure. The average idle time of the room after
      the end of pulmonary procedure and start of next case or end of shift at 5:00 PM
      if no next case was 58 +/- 53 minutes. In 17/51 (33%) patients the room's idle
      time was >60 minutes. A total of 52.3% of patients had the wait time >2 days and
      11% had it >= 6 days, reason in 15/21 (71%) being unavailability of the slot.
      CONCLUSIONS: Most pulmonary procedures were delayed due to spillover of the
      gastrointestinal and surgical cases into the block time allocated to pulmonary
      procedures. The most common reason for difficulty encountered in scheduling the
      pulmonary procedure was slot unavailability. This caused increased procedure
      waiting time. The strategies to reduce procedure delays and turnaround times,
      along with improved scheduling methods, may have a favorable impact on the volume
      of procedures performed in the unit thereby optimizing the existing resources.

PMID- 24739688
TI  - Bronchial venous plexus in left ventricular dysfunction.
AB  - Chronic pulmonary venous hypertension causes dilatation and engorgement of
      bronchial veins because of a close communication between bronchial and pulmonary
      veins. We report a case of severe left ventricular systolic dysfunction with
      chronically elevated pulmonary venous pressure leading to characteristic
      bronchoscopic findings of engorgement of bronchial veins. 

PMID- 24739689
TI  - Mounier-Kuhn syndrome.
AB  - Mounier-Kuhn syndrome or congenital tracheobronchomegaly is a rare clinical and
      radiologic condition. It is characterized by a tracheal and bronchial dilation.
      Fewer than 100 cases have been reported in the medical literature since the
      original description in 1932. The first utilization of bronchoscopy for diagnosis
      of this condition was recorded by Lemoine only in 1949. The cause of this
      condition is not clearly understood; however, histopathologic findings of atrophy
      of smooth muscles and elastic tissue in the trachea and main bronchi have been
      observed. Tracheobronchomegaly can be associated with tracheal and bronchial
      diverticuli. 

PMID- 24739690
TI  - Recurrent hydrothorax and surgical diaphragmatic repair: report of 2 cases and
      review of the literature.
AB  - BACKGROUND: Pleural effusions may result from intra-abdominal processes and
      sometimes present with dramatic clinical consequences. We present 2 cases of
      recurrent hydrothorax requiring surgical repair of diaphragmatic defects and
      describe when surgery may be the best treatment modality. PATIENT 1: : A 63-year
      old man with end-stage renal disease requiring peritoneal dialysis presented with
      dyspnea on exertion that progressed to cardiac arrest. He was found to have a
      tension hydrothorax that was initially stabilized with thoracentesis and tube
      thoracostomy. He eventually underwent surgical repair of fenestrations with
      complete resolution of his effusion. PATIENT 2:: A 52-year-old man with recurrent
      hydrothorax in the context of hepatitis C cirrhosis and hepatocellular carcinoma
      following radiofrequency ablation to his liver had recurrent admissions with
      dyspnea and a large pleural effusion. When medical therapy failed, he underwent
      surgical repair of a large diaphragmatic defect. CONCLUSIONS: Hydrothorax related
      to peritoneal dialysis or cirrhosis may cause life-threatening scenarios in which
      medical management may stabilize the patient. Ultimately, surgical corrections of
      diaphragmatic defects may be necessary for definitive management in selected
      patients. Although these scenarios are rare, clinicians should be aware of these
      possibilities as early collaboration between medical and surgical services is
      essential for optimal patient care.

PMID- 24739691
TI  - Inflammatory pseudotumor of the pleura.
AB  - Inflammatory pseudotumors are rare solid, non-neoplastic masses that can mimic
      pulmonary malignancy. It occurs most commonly in children and young adults and is
      usually found incidentally. There are many reports of the existence of this tumor
      in various organs in the human body. The occurrence of this tumor exclusively in
      the pleura has not been described before. We present a case of inflammatory
      pseudotumor of the pleura and its successful management. 

PMID- 24739692
TI  - Unusual triad of obstructive sleep apnea, uncontrolled hypertension, and severe
      hypokalemia due to ectopic adrenocorticotropic secretion.
AB  - Ectopic adrenocorticotropic hormone secretion is responsible for 12% to 17% of
      all cases of the Cushing syndrome. One of the most commonly described causes of
      ectopic adrenocorticotropic hormone secretion is small cell carcinoma of the
      lung. A rare cause includes a functioning neuroendocrine tumor traditionally
      known as carcinoids that account for 5% of all mediastinal tumors. To our
      knowledge, all reported cases of mediastinal carcinoids are thymic in origin and
      only a minority of those is functional. We present a male patient with
      hypertension, obstructive sleep apnea, and acid-base disorder, in whom further
      investigation revealed an anterior mediastinal mass and Cushing syndrome. 

PMID- 24739693
TI  - Pill aspiration presenting as an endobronchial tumor.
AB  - Tracheobronchial foreign body aspiration is a major cause of morbidity and
      mortality. The incidence of foreign body aspiration decreases significantly with
      increasing age, resulting in atypical presentations in adults. A high index of
      suspicion is required in adults presenting with respiratory symptoms. We present
      a rare case of a foreign body (pill) aspiration in an elderly female mimicking an
      obstructing endobronchial lesion. 

PMID- 24739694
TI  - Pseudomembranous tracheobronchitis caused by Rhizopus sp. After allogeneic stem
      cell transplantation.
AB  - Invasive fungal infections are a major cause of morbidity and mortality in
      allogeneic stem cell transplant recipients. They can occasionally involve the
      tracheobronchial tree with serious clinical consequences. Tracheobronchial
      involvement is often an unexpected finding during diagnostic bronchoscopy.
      Herein, we report a case of pseudomembranous tracheobronchitis caused by Rhizopus
      sp. in an allogeneic stem cell transplant recipient. 

PMID- 24739695
TI  - A distal airway foreign body removed with electromagnetic navigation
      bronchoscopy.
AB  - Distal airway foreign bodies can be challenging to remove with a flexible
      bronchoscope because of angulation or deep impaction. Thoracic surgery may be
      required if bronchoscopy is not successful. The use of electromagnetic navigation
      for pulmonary nodule localization and characterization is well established;
      however, its use to localize and remove distal foreign bodies has not been
      described. We report the initial case of electromagnetic navigation-assisted
      foreign body removal. 

PMID- 24739696
TI  - Novel treatment of a persistent bronchopleural fistula using a customized spigot.
AB  - An abnormal communication between the bronchus and the pleural cavity is known as
      a bronchopleural fistula (BPF). The incidence of postoperative BPF ranges from
      1.5% to 28%, and is responsible for considerable morbidity and mortality. Various
      modalities have been used for treatment of BPF including surgery and
      endobronchial occlusion devices. The scope of therapy is limited in developing
      countries because of cost constraints and lack of availability of different
      occlusion devices. A novel method of BPF closure using a customized spigot and
      cyanoacrylate glue is described. 

PMID- 24739697
TI  - The use of CP-EBUS-TBNA in the diagnosis of chondrosarcoma in a patient With
      Maffucci syndrome.
AB  - We report a case of a 52-year-old white woman with Maffucci syndrome, a rare
      skeletal disorder characterized by multiple cartilage-forming tumors
      (enchondromas). She was referred for evaluation of an enlarging pulmonary nodule.
      Her positron emission tomography-computed tomography scan revealed a low-density,
      tubular lesion in the superior segment of the left lower lobe of the lung. She
      underwent a convex-probe endobronchial ultrasound (CP-EBUS)-guided transbronchial
      needle aspiration (TBNA) that confirmed metastatic chondrosarcoma. Although CP
      EBUS-TBNA has become an established tool for diagnosing and staging of non-small
      cell lung cancer, analysis of samples from rare tumors such as sarcomas by
      cytology alone is often inadequate and histologic confirmation using more
      invasive procedures is often required. Interestingly in our case, the diagnosis
      of chondrosarcoma was established from the cytology specimen obtained with a 21-G
      needle without the need for further tissue sampling. Moreover, the location of
      the lesion was the superior segment of the left lower lobe, an area typically not
      accessible by CP-EBUS, due to the size of the airway. Considering together, the
      successful diagnosis of a rare tumor such as sarcomas by CP-EBUS-TBNA modality
      indicates the growing importance of this minimally invasive technology. 

PMID- 24739698
TI  - Quadrivial pattern of division in the right upper lobe: the axillary bronchus.

PMID- 24739699
TI  - Guidewire-assisted technique for placement of endobronchial Watanabe Spigots.

PMID- 24739700
TI  - Providing and funding breast health services in urban nurse-managed health
      centers.
AB  - Nurse-managed health centers (NMHCs) are an innovative health care delivery model
      that serves as an important point of health care access for populations at risk
      for disparities in health outcomes. This article describes the process and
      outcomes of clinical breast health services in two NMHCs located in a large
      Midwestern city. Findings indicate that client's knowledge about breast health
      was increased after they received breast health services from NMHC nurses.
      Significant positive changes in behavior related to the early detection of breast
      cancer were found in the study. NMHCs, identified for expansion in the Patient
      Protection and Affordable Care Act, offer a unique health care services delivery
      model that promotes access to care and early identification of breast cancer in
      very low-income and uninsured women. 

PMID- 24739701
TI  - Important compositional characteristics in the clinical use of adhesive systems.
AB  - Improvements in dentin bonding systems have influenced modern restorative
      dentistry. The desire for minimal invasiveness has resulted in more-conservative
      cavity design, which basically relies on the effectiveness of current dentin
      bonding systems. Interaction of adhesives with enamel and dentin is based on two
      systems, commonly described as etch-and-rinse and self-etch. Priming and bonding
      agents can be separate or combined, resulting in two- or three-step systems for
      etch-and-rinse adhesives and one- or two-step systems for self-etch adhesives.
      Self-etch systems use acidic functional monomers that simultaneously demineralize
      and impregnate tooth structures. Etch-and-rinse and self-etch systems have
      advantages and disadvantages, which are primarily related to the simplified
      bonding procedures required under clinical conditions. Knowledge of the
      composition, characteristics, and mechanisms of adhesion for each adhesive system
      is critical in selecting the ideal adhesive materials for clinical use.

PMID- 24739702
TI  - Physicomechanical properties of a zinc-reinforced glass ionomer restorative
      material.
AB  - We compared a zinc-reinforced glass ionomer restorative material (ChemFil Rock)
      with three commercially available glass ionomer cements (GICs), namely, Fuji IX
      GP Extra, Ketac Molar Quick Aplicap, and EQUIA Fil, with respect to fracture
      toughness, microhardness, roughness, and abrasive wear. Fracture toughness (KIC)
      was tested according to ISO 13586 (n = 10). Hardness, roughness, and abrasive
      wear were also tested (n = 9). Data were analyzed using the Wilcoxon rank-sum
      test with adjustment for multiple comparisons (alpha = 0.05). As compared with
      the other GICs ChemFil Rock exhibited a greater increase in surface roughness (P
      < 0.05) and lower microhardness (P < 0.01). The wear resistance of ChemFil Rock
      was comparable to that of the other GICs (P > 0.05). ChemFil Rock had
      significantly lower fracture toughness as compared with EQUIA Fil (P = 0.01) and
      significantly higher fracture toughness as compared with the other GICs (P <
      0.02). In conclusion, as compared with the three other commercially available
      GICs, ChemFil Rock had intermediate fracture toughness, the lowest microhardness,
      and the greatest change in surface roughness.

PMID- 24739703
TI  - Effect of basic fibroblast growth factor on angiogenesis and bone regeneration in
      non-critical-size bone defects in rat calvaria.
AB  - We used microcomputed tomography (micro-CT) to evaluate the effects of basic
      fibroblast growth factor (FGF-2) contained in absorbable collagen sponges on
      angiogenesis and bone regeneration in rat calvarial non-critical-size bone
      defects. Two symmetrical non-critical-size calvarial bone defects (diameter, 2.7
      mm) were created in male Fisher rats. An absorbable collagen sponge with or
      without FGF-2 (0.1% or 0.3%) was implanted into each defect. Blood vessel volume
      and bone volume were calculated using software. On day 28, blood vessel volume
      and bone volume were significantly greater in the 0.3% and 0.1% FGF-2 groups than
      in the control group. FGF-2 concentration-dependently increased blood vessels and
      bone formation in non-critical-size bone defects in rat calvaria.

PMID- 24739704
TI  - Effect of a chitosan sponge impregnated with platelet-derived growth factor on
      bone augmentation beyond the skeletal envelope in rat calvaria.
AB  - We evaluated the ability of platelet-derived growth factor (PDGF) to promote bone
      augmentation beyond the skeletal envelope in rat calvaria. The calvariae of 14
      rats were exposed, and two plastic caps-one with 0.03% PDGF and a chitosan sponge
      and one with a chitosan sponge alone-were placed. Microcomputed tomography and
      histologic sections were used to determine the amount of bone augmentation within
      the plastic caps. Bone volume was calculated using measurement software. Bone
      volume and amount of bone augmentation were significantly greater in the PDGF
      group than in the control group. In conclusion, a chitosan sponge containing
      0.03% PDGF enhanced bone formation beyond the skeletal envelope in rat calvaria.

PMID- 24739705
TI  - Biocompatibility of Portland cement combined with different radiopacifying
      agents.
AB  - The aim of this study was to evaluate the response of rat subcutaneous tissue to
      Portland cement combined with two different radiopacifying agents, iodoform
      (CHI3) and zirconium oxide (ZrO2). These materials were placed in polyethylene
      tubes and implanted into the dorsal connective tissue of Wistar rats for 7 and 15
      days. The specimens were then stained with hematoxylin and eosin, and
      inflammatory reaction parameters were evaluated by light microscopy. The
      intensity of the inflammatory response to the sealants was analyzed by two blind
      calibrated observers throughout the experimental period. Histological analysis
      showed that all the materials caused a moderated inflammatory reaction at 7 days,
      which then diminished with time. At 15 days, the inflammatory reaction was almost
      absent, and fibroblasts and collagen fibers were observed indicating normal
      tissue healing. The degrees of the inflammatory reaction on different days
      throughout the experimental period were compared using the non-parametric Kruskal
      Wallis test. Statistical analysis demonstrated no significant differences amongst
      the groups, and Portland cement associated with radiopacifying agents gave
      satisfactory results. Therefore, Portland cement used in combination with
      radiopacifying agents can be considered a biocompatible material. Although our
      results are very encouraging, further studies are needed in order to establish
      safe clinical indications for Portland cement combined with radiopacifying
      agents.

PMID- 24739706
TI  - Passive ultrasonic irrigation in the presence of a low concentration of hydrogen
      peroxide enhances hydroxyl radical generation and bactericidal effect against
      Enterococcus faecalis.
AB  - Chemomechanical procedures can be used to eliminate bacteria from root canals.
      However, detectable bacteria sometimes remain because of the complexity of the
      root canal system. Endodontic passive ultrasonic irrigation (PUI) with hydrogen
      peroxide (H2O2) may be a promising option for increasing bactericidal hydroxyl
      radical (HO*) generation. In this in vitro experiment, we examined the effects of
      HO* generated using PUI and a low concentration of H2O2. An ultrasonic tip was
      submerged in 0.45 mol/L (1.5%) H2O2 in a microfuge tube. H2O2 was activated by an
      ultrasonic unit, the tip of which was kept centered in the tube, to mimic PUI.
      HO* generation was detected by electron spin resonance spectroscopy. An
      Enterococcus faecalis suspension in H2O2 was then preparedand activated as
      described above. Bactericidal effects were assessed by viable counting. Two-way
      analysis of variance and Tukey's test were used to assess the statistical
      significance of differences among groups (P < 0.05). HO* generation and
      bactericidal activity were significantly increased by PUI in H2O2 in a time
      dependent manner and were significantly higher than with H2O2 alone or with PUI
      in a Tris-HCl suspension. These results suggest that PUI in the presence of a low
      H2O2 concentration is a promising new disinfection strategy.

PMID- 24739707
TI  - Isoproterenol facilitates GABAergic autapses in fast-spiking cells of rat insular
      cortex.
AB  - In the cerebral cortex, fast-spiking (FS) cells are the principal GABAergic
      interneurons and potently suppress neural activity in targeting neurons. Some FS
      neurons make synaptic contacts with themselves. Such synapses are called autapses
      and contribute to self-inhibition of FS neural activity. beta-Adrenoceptors have
      a crucial role in regulating GABAergic synaptic inputs from FS cells to pyramidal
      (Pyr) cells; however, the beta-adrenergic functions on FS autapses are unknown.
      To determine how the beta-adrenoceptor agonist isoproterenol modulates inhibitory
      synaptic transmission in the autapses of FS cells, paired whole-cell patch-clamp
      recordings were obtained from FS and Pyr cells in layer V of rat insular cortex.
      Previous studies found that isoproterenol (100 MUM) had pleiotropic effects on
      unitary inhibitory postsynaptic currents (uIPSCs) in FS->Pyr connections, whereas
      autapses in FS cells were always facilitated by isoproterenol. Facilitation of
      autapses by isoproterenol was accompanied by decreases in the paired-pulse ratio
      of second to first uIPSC amplitudes and the coefficient of variation of the uIPSC
      amplitude, which suggests that beta-adrenergic facilitation is likely mediated by
      presynaptic mechanisms. The discrepancy between isoproterenol-induced modulation
      of uIPSCs in FS autapses and in FS->Pyr connections may reflect the presence of
      different presynaptic mechanisms of GABA release in each synapse.

PMID- 24739708
TI  - Adrenergic regulation of GABA release from presynaptic terminals in rat cerebral
      cortex.
AB  - The alpha1-adrenoceptor agonist phenylephrine and the beta-adrenoceptor agonist
      isoproterenol have opposite effects on evoked EPSPs (eEPSPs) in the cerebral
      cortex. The suppressive effects of phenylephrine on eEPSPs are mediated by
      modulation of postsynaptic glutamate receptors, whereas enhancement of eEPSPs by
      isoproterenol is due to facilitation of glutamate release from presynaptic
      terminals. The present study used whole-cell patch-clamp recordings from layer V
      pyramidal neurons in visuocortical slice preparations to assess the effects of
      phenylephrine and isoproterenol on the release probability of gamma-aminobutyric
      acid (GABA). The present study recorded evoked inhibitory postsynaptic potentials
      (eIPSCs) by repetitive electrical stimulation (duration, 100 MUs; 10 stimuli at
      33 Hz) and miniature IPSCs (mIPSCs). The effects of phenylephrine (100 MUM)
      depended on the amplitude of eIPSCs: phenylephrine decreased the paired-pulse
      ratios (PPRs) of eIPSCs with smaller amplitudes (<~600 pA) but increased PPRs of
      eIPSCs with larger amplitude. Phenylephrine also exhibited amplitude-dependent
      modulation of mIPSCs, i.e., an increase in the frequency of smaller mIPSC events
      (<~20 pA) and a decrease in the frequency of larger events. These findings
      suggest that alpha1-adrenoceptor activation facilitates GABA release from a
      subpopulation of GABAergic terminals that induce smaller-amplitude IPSCs in
      postsynaptic neurons. In contrast, isoproterenol (100 MUM) consistently decreased
      the PPR of eIPSCs and increased the frequency of mIPSCs, suggesting that
      presynaptic beta-adrenoceptors increase release probability from most GABAergic
      terminals. The complexity of adrenoceptor modulations in GABAergic synaptic
      transmission by alpha1-adrenoceptor and beta-adrenoceptor activation may be due
      to the presence of pleiotropic subtypes of GABAergic interneurons in the cerebral
      cortex.

PMID- 24739709
TI  - Root proximity and stability of orthodontic anchor screws.
AB  - This study aimed to investigate a causal relationship between the stability of
      orthodontic anchor screws (screws) and the degree of their proximity to the root
      (root proximity) using mobility test device (Periotest) and cone-beam computed
      tomography (CBCT). In total, 165 (diameter 1.6 mm; length 8 mm) screws in 58
      patients (average age, 24.4 +/- 8.5 years) were evaluated. After screw placement,
      CBCT was used for diagnostic imaging of the area around the site. Root proximity
      was evaluated and categorized into three groups: A, no contact; B, single
      contact; and C, multi-contact. The Periotest value was used to assess screw
      stability. The screw failure rate according to root proximity significantly
      differed between categories A and C. In addition, failure rate significantly
      differed between mandibular screws with and without root contact. Periotest
      values in categories A and C were significantly higher in the mandible than in
      the maxilla. Mandibular screws had greater mobility than maxillar screws, even
      when the screw avoided root contact. The lower stability of mandibular screws
      with root contact might be related to their greater mobility.

PMID- 24739710
TI  - Melatonin regulates human bone sialoprotein gene transcription.
AB  - Melatonin is produced by the pineal gland and regulates various physiological
      processes including osteoblast differentiation and bone formation. Bone
      sialoprotein (BSP) is a mineralized connective tissue-specific protein expressed
      in the early stage of cementum and bone mineralization. To elucidate the effects
      of melatonin on human BSP gene expression, we utilized human Saos2 osteoblast
      like cells. Melatonin (100 nM) increased the level of BSP mRNA at 3 h, and the
      level became maximal at 12 and 24 h. We then investigated the melatonin-induced
      transcriptional activity of luciferase constructs (between -84LUC and -868LUC)
      including different lengths of the human BSP gene promoter transfected into Saos2
      cells. The effects of melatonin abrogated in constructs included 2-bp mutations
      in the two cAMP response elements (CRE1 and CRE2). The effects of melatonin were
      suppressed by protein kinase A, tyrosine kinase, ERK1/2 and phosphatidylinositol
      3-kinase inhibitors. Gel mobility shift assays showed that melatonin increased
      the binding of nuclear proteins to CRE1 and CRE2, and antibodies against CRE
      binding protein 1 (CREB1), phospho-CREB1, c-Fos, c-Jun, JunD and Fra2 disrupted
      CRE1 and CRE2 protein complex formation. These data indicate that melatonin
      induces BSP transcription via the CRE1 and CRE2 elements in the human BSP gene
      promoter. (J Oral Sci 56, 67-76, 2014). 

PMID- 24739711
TI  - Midazolam inhibits IgE production in mice via suppression of class switch
      recombination.
AB  - Anaphylactic shock is characterized by increased capillary permeability and a
      decline in blood pressure due to excessive production of IgE. Midazolam (MDZ) is
      reported to have immunomodulatory properties. However, little is known about the
      effect of MDZ on the production of IgE antibody. We examined whether MDZ can
      suppress antigen-specific and total IgE production followed by IgE class switch
      recombination (CSR). MDZ was administered intraperitoneally to mice prior to
      ovalbumin (OVA) plus native cholera toxin (nCT) immunization. Serum OVA-specific
      and total IgE responses, and surface IgE-positive B cells were analyzed by ELISA
      and flow cytometry. Furthermore, expression levels of CSR-associated molecules
      such as germ-line transcript epsilon (epsilonGLT), germ-circle tanscript epsilon
      (epsilonCT), AID, and Id2 in the spleen were compared. The levels of interferon
      gamma (IFN-gamma) and interleukin (IL)-4 mRNA and protein were also examined in
      the spleen and serum. MDZ significantly suppressed OVA-specific and total IgE
      levels in plasma and surface IgE-positive B cells in the spleen. Moreover, MDZ
      treated mice had significantly reduced levels of epsilonGLT and epsilonCT.
      Furthermore, although the levels of IFN-gamma mRNA and protein were significantly
      elevated, those of IL-4 were reduced in MDZ-treated mice. Therefore, MDZ may be
      an important modulator of allergic responses through its ability to downregulate
      IgE production.

PMID- 24739712
TI  - Oral opportunistic infections in institutionalized patients with motor and
      intellectual disabilities.
AB  - To establish a basic strategy for prevention of aspiration pneumonia in patients
      with motor and intellectual disabilities, we investigated oral opportunistic
      pathogen (OOP) infections in 31 such patients who were resident at a welfare
      home. Patients received special oral care from a dental hygienist once a week.
      OOP samples were collected by scraping the dorsal surface of the tongue, and then
      cultured. For each patient, the basic reasons for admission and the degree of
      intellectual disability and mobility were recorded. OOPs were found in 61.3% of
      the patients, of which methicillin-sensitive Staphylococcus aureus (MSSA) was the
      most commonly detected (38.7%). A significantly high proportion of male patients
      were OOP-positive, and a significantly high proportion of patients with mental
      retardation were Candida sp.-positive. However, multivariate logistic regression
      revealed that disability was not associated with OOP positivity. No correlation
      was found between OOP positivity and disability. Nevertheless, special oral care
      may be beneficial for maintenance of oral health in patients with disabilities.

PMID- 24739713
TI  - Surgical approach to snus-induced injury of the oral mucosa.
AB  - Snus (Swedish moist snuff) causes lesions in the oral mucosa at the location
      where pinches are regularly placed. In addition, some patients develop
      irreversible local gingival recession and sometimes ulcers with perforations to
      the roots. Such injuries lead to denuded roots that are at risk for caries and
      periodontal disease, with subsequent esthetic consequences. Therapy for
      irreversible local gingival recession is currently lacking. In the present
      report, we describe two cases of successful surgical treatment for irreversible
      lesions caused by snus.

PMID- 24739714
TI  - Guided bone regeneration following surgical treatment of a rare variant of
      Pindborg tumor: a case report.
AB  - Calcifying epithelial odontogenic tumor is a benign neoplasm, but its local
      destructive potential may lead to the formation of major bone defects.
      Microscopically, there are some histological variants. Among them, we highlight
      the clear cell variant due to its more aggressive behavior and a higher incidence
      of relapse. In this context, it is pertinent to describe the clear cell variant
      of calcifying epithelial odontogenic tumor. Despite the large bone defect formed
      in the posterior region of the mandible, conservative treatment associated with
      guided bone regeneration assured complete bone formation and the absence of
      recurrence in an 8-year follow-up period.

PMID- 24739715
TI  - [What can we do for standardized diagnosis and treatment of pediatric acquired
      aplastic anemia].

PMID- 24739716
TI  - [Immunosuppressive therapy using antithymocyte globulin and cyclosporin A with or
      without human granulocyte colony-stimulating factor in children with acquired
      severe aplastic anemia].
AB  - OBJECTIVE: To compare the efficacy and safety of four different regimens for
      pediatric severe aplastic anemia (SAA) with immuno-suppressive therapy (IST) with
      or without combined human granulocyte colony-stimulating factor (G-CSF). METHOD:
      The authors retrospectively analyzed 105 children with SAA treated with IST with
      or without G-CSF in the hospital from February 2000 to September 2010. Regimen A,
      without G-CSF in the whole treatment, was used to treat Group A patients, n = 27;
      Regimen B, G-CSF, was initiated in Group B, n = 24, before the IST until
      hematologic recovery; Regimen C, G-CSF, was used together with the IST for Group
      C patients, n = 24, until hematologic recovery; Regimen D,G-CSF was used for
      Group D, n = 30, after the end of IST until hematologic recovery. The response
      rate, relapse rate, mortality, infection rate, infection-related death rate, risk
      of evolving into MDS/AML, survival rate, factors affecting the time of event-free
      survival and so on. RESULT: (1) The response (CR+PR) rates 4, 6, 12 and 24 months
      after IST of the whole series of 105 SAA children were 50.5% (7.6%+42.9%) , 60.0%
      (21.9%+38.1%) , 67.6% (38.1%+29.5%) and 69.5% (40.0%+29.5%) respectively. The 2
      year survival rate was 90.5%; the follow-up of the patients for 13 years showed
      that the whole survival rate was 87.6%. (2) The differences of the response rates
      4, 6, 12 and 24 months after IST of the 4 groups were not significant (P > 0.05).
      (3) No significant differences were found in the mortalities 4, 6, 12 and 24
      months among the 4 groups (P > 0.05). (4) Of the 105 patients, 4 children had
      relapsed disease in the period of time from 6 to 24 months after IST. All the
      four patients belonged to the groups with G-CSF. (5) The use of G-CSF could not
      decrease the infection period before IST (day) (P = 0.273), and it had no impact
      on the infection rate after IST (P = 0.066). It did not reduce the rates of
      septicemia and infectious shock. And to the infection-related death rate no
      significant conclusion can be made. (6) Follow up of the patients for 13 years,
      showed that 2 had the evolution to MDS/AML in the 105 patients and the two
      children belonged to the groups with G-CSF. (7) Kaplan-meier curve analysis did
      not show any differences in the survival rates of the four groups. (8) Cox
      regression analysis showed that the use of G-CSF had no benefit to the patients'
      long term survival. While the age of diagnosis and the infection history before
      IST were significantly related to the patients' long term survival. CONCLUSION:
      The use of G-CSF did not contribute to the early response and could not reduce
      the infection rate, infection-related death rate and the patients' long term
      survival. There were no significant differences in the survival rates of the four
      groups. Attention should be paid to the risk of the evolution to MDS/AML.

PMID- 24739717
TI  - [Liver and heart iron deposition status in patients with beta thalassemia major:
      a multicenter study].
AB  - OBJECTIVE: To observe the status of iron deposition in patient with beta
      thalassemia major, and to formulate appropriate treatment strategies. METHOD: The
      data of status of transfusion and chelation in 135 patients aged from 6 years and
      4 months to 17 years and 11 months with beta thalassemia major were collected and
      analyzed. Serum ferritin levels were determined and cardiac and hepatic iron
      deposition was determined using MRI T2(*) technology. RESULT: Of the 135 cases
      studied, 66 were male, and 69 were female, their average age was 12.1 years.
      Serum ferritin (SF) was determined for 111 cases, it varied from 1 086.8 ug/L to
      15 011.5 ug/L. Among them, 16 cases had SF level <2 000 ug/L (14.5%) , in 41
      cases SF were between 2 000 and 4 000 ug/L (36.0%) ;in 54 cases SF >4 000 ug/L
      (48.7%) . Liver MRI T2(*) results showed that in only 8 cases (5.9%) iron content
      in the liver was in normal range, 19 cases (14.9%) showed mild liver iron
      deposition;34 (25.2%) moderate and 74 (54.8%, the youngest one was only 6 years
      and 4 months of age) had severe iron deposition respectively. Cardiac MRI T2(*)
      showed that in 89 cases (65.9%) iron content in the heart was in normal range;19
      cases (14.1%) had mild cardiac iron deposition and 27 (20.0%) presented severe
      iron deposition (the youngest one was only 9 years and 3 months of age) . SF
      level was obviously related to liver and cardiac iron deposition (MRI T2(*)) r
      and P value were -0.284, 0.003 and -0.374, 0.000 respectively. In 108 cases
      regular transfusion and chelation were delayed due to financial problem. The late
      and insufficient dosage administered and irregular chelation caused the higher SF
      level and the severe iron deposition. CONCLUSION: The survival status of beta
      thalassemia major in China is worrisome. Majority of them had not received
      regular transfusion and chelation. Liver and cardiac iron deposition occur early
      and had a high incidence.

PMID- 24739718
TI  - [Allogeneic hematopoietic stem cell transplantation for hemophagocytic syndrome].
AB  - OBJECTIVE: To observe the conditioning regimen, efficacy and side effects of
      allogeneic hematopoietic stem cell transplantation (allo-HSCT) for hemophagocytic
      lymphohistiocytosis (HLH). METHOD: From 2010 to 2012, a total of 11 cases after
      allo-HSCT were evaluated including 8 cases with familial hemophagocytic
      lymphohistiocytosis (FHL) and 3 cases with Epstein-Barr virus (EBV) related HLH.
      Allo-HSCT from HLA haploidentical HSCT was performed for 3 cases and unrelated
      allo-HSCT for 8 cases; 7 cases underwent allo-HSCT with conditioning regimen of
      etoposide (VP16), busulphan (Bu), fludarabine (Flu) and antilymphocyte globulin
      (ATG) and 4 cases with Flu, melphalan (Mel) and ATG. Cyclosporine (CsA) or
      tacrolimus, mycophenolate (MMF) and methorexate (MTX) were used for prevention of
      graft versus host disease (GVHD). Four cases received anti-CD25 MoAbs, 7 cases
      received cord blood and 1 of them received haploidentical bone marrow to prevent
      GVHD. RESULT: Three cases died after allo-HSCT. The median overall survival time
      of the 8 cases evaluated was 585 days (154-1 115 d). All the patients were
      successfully engrafted. Acute GVHD (aGVHD) occurred in 8 cases, including 3 cases
      of gradeI/II and 5 cases of grade III/IV. Chronic GVHD (cGVHD) occurred in 4
      cases. Seven cases had cytomegalovirus (CMV) reactivation. CONCLUSION: The allo
      HSCT was successful in treating primary and refractory hemophagocytic syndrome.

PMID- 24739719
TI  - [A cross-sectional survey of coagulation factor VIII inhibitor in children with
      hemophilia A].
AB  - OBJECTIVE: To study the current situation of coagulation factor VIII (FVIII)
      inhibitor development in children with hemophilia A (HA) through a cross
      sectional survey, and to explore the risk factors of inhibitor development in
      order to provide evidence for further prevention and management strategies.
      METHOD: The clinical data of outpatients with hemophilia A in Beijing Children's
      Hospital seen from November 2012 to May 2013 were collected, FVIII inhibitor was
      screened and analyzed its risk factors. RESULT: A total of 102 HA children were
      enrolled, 5 were mild cases, 32 were moderate, and 65 were severe cases; the
      median age on enrollment was 55.5 (3.0-200.0) months:19(18.6%) of patients had
      inhibitors and 9 (8.8%) had low-titer inhibitors, 10 (9.8%) had high-titer
      inhibitors. Receiving FVIII treatment for life-threatening bleeding (P = 0.03)
      ,OR 4.10 (95%CI:1.17-14.32) was a risk factor for inhibitor generation and
      patients within 20 exposure days have more chances of inhibitor development (P =
      0.04) ,OR 3.32 (95%CI:1.02-10.86) . High and intense FVIII exposure within short
      term was the risk factor for high titer inhibitor development (P = 0.01) ,OR 5.25
      (95%CI:1.45-21.92) . CONCLUSION: Intense FVIII exposure for severe hemorrhage was
      the risk factor of inhibitors development especially of high titer inhibitors.

PMID- 24739720
TI  - [Recommendations for diagnosis and treatment of acquired aplastic anemia in
      children].

PMID- 24739721
TI  - [Relationship between the level of sialic acid during perinatal period and early
      intelligence development of full term infants].
AB  - OBJECTIVE: To investigate the correlation between the status of sialic acid (SA)
      during perinatal period and early intelligence development of healthy full term
      infant, and to explore the effect of SA on the early intelligence development.
      METHOD: A total of 127 pairs of healthy mothers-neonates in the Affiliated
      Hospital of Nantong University were recruited randomly in this prospective cohort
      study. The levels of SA from body fluids of mothers-neonates were measured by
      enzyme-linked immunosorbent assay, such as the full-term maternal and cord blood
      and the colostrum. The questionnaire surveys were carried out in mothers and
      mental development evaluation according to Children's Development Center of China
      (CDCC) were carried out in infants 3 to 4 months of age to obtain the mental
      development index (MDI) and psycho-motor development index (PDI). RESULT: A total
      of 120 pairs of maternal-neonatal subjects with complete data were included into
      statistical analysis. The levels of SA of maternal and cord blood and colostrum
      were (2.25 +/- 0.02), (1.21 +/- 0.01), and (5.01 +/- 0.06) mmol/L respectively.
      MDI and PDI of infants 3 to 4 months of age were (99.40 +/- 1.87) and (98.53 +/-
      1.96). The analysis using multiple linear regression indicated that MDI was
      associated with SA levels of cord blood and colostrum (beta = 0.636, 0.175, P <
      0.05), and PDI was also associated with them (beta = 0.502, 0.262, P < 0.05). The
      levels of SA of cord blood and colostrums were individually divided into high
      level group and low-level one according to the median level. MDI and PDI in high
      level group of cord blood were both significantly higher than that in low-level
      group (111.85 +/- 2.79) vs. (108.88 +/- 2.0) , (101.08 +/- 4.44) vs. (98.88 +/-
      2.0) P < 0.01. So were MDI and PDI in high-level group of colostrum compared with
      those in low-level group (111.71 +/- 3.07) vs. (108.81 +/- 1.56), P < 0.01;
      (101.29 +/- 4.23) vs.(98.56 +/- 1.79), P < 0.05. The analysis on correlation
      between the levels of maternal-neonatal body fluids showed that the level of SA
      of colostrum was positively correlated with that of cord blood (r = 0.507, P =
      0.004). However, no correlation was found either between the level of SA of
      maternal and cord blood or between the level of SA of maternal blood and
      colostrums. Further division into high-level and low-level groups was done
      according to the median level of maternal blood. The levels of SA of colostrum
      and cord blood in high-level group were markedly higher than those in low-level
      one (5.12 +/- 0.35) vs. (4.87 +/- 0.22) and (1.21 +/- 0.02) vs. (1.17 +/- 0.01),
      P < 0.05. CONCLUSION: High levels of SA of cord blood and colostrums might be
      beneficial to the early intelligence development of full term infant. Abundant
      intake of SA during perinatal period and good function of placenta may play
      important role in early intelligence development.

PMID- 24739722
TI  - [Analysis of a case with typical Hutchinson-Gilford progeria syndrome with
      scleroderma-like skin changes and review of literature].
AB  - OBJECTIVE: To explore clinical, radiographical and genetic characteristics of
      classical Hutchinson-Gilford progeria syndrome (HGPS). METHOD: Data of a case of
      HGPS diagnosed at Tongji Hospital Affiliated to Tongji Medical College of
      Huazhong University of Science and Technology was analyzed and related literature
      was reviewed. RESULT: At the age of 8 months, the affected-infant presented with
      characteristic manifestation such as short stature, low weight, frontal bossing,
      alopecia, prominent scalp veins, micrognathia with a vertical midline groove in
      the chin, sclerodermatous skin, knee joints contracture with a horse-riding
      stance, and limited range of movement of ankle joints. Blood test showed blood
      platelet count (416-490) *10(9)/L. Lower extremities MRI showed reduced
      subcutaneous fat. LMNA gene analysis showed that the affected-infant carried
      typical heterozygous mutation: c. 1824C>T (p. G608G), while his parents were
      normal. At the age of 13 months, X-rays showed short distal phalanges and
      clavicles with acro-osteolysis. After following up for 15 months, his appearance
      of progeria became more apparent. As far as we know, there are only 2 cases of
      classical HGPS confirmed by gene analysis in China. CONCLUSION: Classical HGPS
      should be considered when infants appeared with sclerodermatous skin. Genetic
      analysis could help to diagnose classical HGPS as early as possible and avoid
      unnecessary investigations. In addition, affected-infants need to be long term
      followed-up and provided genetic counseling.

PMID- 24739723
TI  - [Non-invasive mechanical ventilation in a child with central hypoventilation
      syndrome: one year follow-up].
AB  - OBJECTIVE: To investigate clinical features and therapeutic methods of late-onset
      central hypoventilation syndrome. METHOD: A nine-year old boy was trachea
      intubated and mechanically ventilated because of pneumonia, respiratory and heart
      failure and pulmonary hypertension. It was found that hard to extubate the
      patient as he was breathing normally while awake but had shallow breathing,
      oxygen desaturation and CO2 retention when falling asleep. Nocturnal
      polysomnography together with transcutaneous CO2 supported the diagnosis of
      central hypoventilation. The final diagnosis was late-onset congenital central
      hypoventilation syndrome as the patient gained weight rapidly since 3 years of
      age and the brain magnetic resonance imaging (MRI) and genetic screening were
      unremarkable. RESULT: The patient was treated with bi-level positive air pressure
      ventilation via nasal mask which showed good oxygen saturation and CO2 dropped
      down. The follow up study done one year later showed normal brain MRI, relief of
      pulmonary hypertension and better CO2 level in both awaken and sleeping status.
      CONCLUSION: The late-onset congenital central hypoventilation syndrome in this
      case had onset of symptoms at 2 years of age, he had normal breathing while he
      was awake but had oxygen desaturation and CO2 retention during sleep, therefore,
      respiratory support is required in severe cases. Mechanical ventilation via
      tracheotomy and non-invasive ventilation via mask are the major choice.

PMID- 24739724
TI  - [Clinical analysis of 4 children with negative pressure pulmonary edema].
AB  - OBJECTIVE: To analyze the clinical characteristics of negative pressure pulmonary
      edema (NPPE). METHOD: A retrospective investigation of the clinical
      manifestation, imageology, clinical course and outcome of 4 children with NPPE
      seen between June 2012 and July 2013 in a children's hospital. The causation of
      the airway obstruction was also explored. RESULT: All the 4 cases were boys, the
      range of age was 40 days to 9 years. They had no history of respiratory and
      circulatory system disease. In 3 cases the disease had a sudden onset after the
      obstruction of airway, and in one the onset occurred 1.5 hours after removing the
      airway foreign body. All these cases presented with tachypnea, dyspnea, and
      cyanosis, none had fever. Three cases had coarse rales. Chest radiography was
      performed in 3 cases and CT scan was performed in 1 case, in all of them both
      lungs displayed diffuse ground-glass-like change and patchy consolidative
      infiltrates. Three cases were admitted to the ICU, duration of mechanical
      ventilation was less than 24 hours in 2 cases and 39 hours in one. Oxygen was
      given by mask to the remaining one in emergency department, whose symptoms were
      obviously improved in 10 hours. None was treated with diuretics, glucocorticoids
      or inotropic agents. Chest radiographs were taken within 24 hours of treatment in
      2 cases and 24-48 hours in the other 2; almost all the pulmonary infiltrates were
      resolved. All the 4 cases were cured. The causes of airway obstruction were
      airway foreign bodies in two cases, laryngospasm in one and laryngomalacia in the
      other. CONCLUSION: NPPE is a life-threatening emergency, which is manifested by
      rapid onset of respiratory distress rapidly (usually in several minutes, but
      might be hours later) after relief of the airway obstruction, with findings of
      pulmonary edema in chest radiograph. The symptoms resolve rapidly by oxygen
      therapy timely with or without mechanical ventilation. In children with airway
      obstruction, NPPE should be considered.

PMID- 24739725
TI  - [Effect of thrombelastography in the diagnosis of disseminated intravascular
      coagulation in children].
AB  - OBJECTIVE: To study the effect of thrombelastography (TEM) in the diagnosis of
      disseminated intravascular coagulation (DIC) in children. METHOD: The data of 117
      children suffering from DIC in the pediatric intensive care unit (PICU) and
      Cardiologic ICU (CICU) in the authors' hospital from January 2010 to June 2012
      were collected. Ninety-four children without DIC were enrolled into the control
      group. The platelet count, prothrombin time (PT), activated partial
      thromboplastin time (APTT), fibrinogen (FIB), D-dimers and TEM were determined.
      The sensitivity and specificity of TEM were measured and the relevance of TEM and
      DIC was investigated to evaluate the effect of TEM and the conventional tests of
      the coagulation system in the diagnosis of DIC in children. RESULT: The average R
      reaction time in the DIC group was significantly longer than that in the control
      group[(13.3 +/- 3.3)s vs. (4.5 +/- 2.6)s, P = 0.000 5], and the average alpha
      angle in the DIC group was smaller than that in the control group significantly
      (37.2 degrees  +/- 1.4 degrees  vs. 55.6 degrees  +/- 3.8 degrees , P = 0.001 0).
      There was significant decrease in the maximal amplitude (MA) and amplitude (A) in
      the DIC group, compared with the control group. The OR value (95%CI) of the R
      reaction time,alpha-angle and MA was 3.538 (1.298-5.389), 2.472 (1.820-2.224) and
      0.256 (0.263-0.831) respectively, which suggests good correlation with the
      existence of DIC (all P < 0.01). The specificity of R reaction time, alpha-angle
      and MA was higher than that of PT, APTT and D-dimers (85.7%, 73.5% and 72.9% vs.
      27.0%, 42.1% and 68.2%) . The average R reaction time of children suffering from
      hemorrhage of severe liver disease(n = 36) was significantly longer than that of
      40 healthy children [(9.2 +/- 2.7) vs. (2.3 +/- 1.8)s, P = 0.001 0], while the
      alpha-angle (42.8 degrees  +/- 7.6 degrees  vs. 59.2 degrees  +/- 10.8 degrees ,
      P = 0.040 0) and the MA value [(33.9 +/- 5.1) vs.(56.0 +/- 8.1) mm, P = 0.020 0]
      were significantly smaller. The average R reaction time of children suffering
      from congenital coagulopathy was significantly longer than that of healthy
      children [(6.8 +/- 3.1) vs. (2.3 +/- 1.8)s, P = 0.003 0], too. CONCLUSION: TEM,
      which has high specificity, is beneficial to the diagnosis of DIC in children.

PMID- 24739726
TI  - [Clinical analysis and follow-up of neonatal purulent meningitis caused by group
      B streptococcus].
AB  - OBJECTIVE: To study the clinical characteristics, antibiotics sensitivity and
      outcome of group B streptococcus (GBS) meningitis in neonates in order to provide
      the guide for early diagnosis and appropriate treatment. METHOD: A retrospective
      review was performed and a total of 13 cases of neonatal purulent meningitis
      caused by GBS were identified in the Neonatal Intensive Care Unit of Yuying
      Children's Hospital of Wenzhou Medical University from January 1, 2005 to May 31,
      2013. The clinical characteristics, antibiotics sensitivity test results and
      outcome were analyzed. RESULT: Fever, poor feeding, seizure and lethargy were
      common clinical signs of neonatal purulent meningitis caused by GBS. Three cases
      of early onset GBS meningitis received prepartum antibiotics. All 13 cases had
      abnormal C-reactive protein (CRP) level, and 11 cases had increased CRP within
      hours after admission. Of the 13 patients, 7 were cured, 4 discharged with
      improvement, 2 patients died during hospitalization after being given up because
      of serious complication. The average length of stay for recovered patients was
      (47 +/- 21)d. Acute complications mainly included hyponatremia (5 cases),
      intracranial hemorrhage (3 cases) , ventriculomegaly (3 cases) , subdural
      collection (2 cases) , hydrocephalus (2 cases), septic shock (2 cases), cerebral
      hernia (1 case), encephalomalacia (1 case). One preterm patient with early onset
      GBS meningitis died 1 month after hospital discharge. Among 7 survivors with 10
      24 months follow-up, 3 were early onset GBS meningitis, 2 with normal results of
      neurologic examination, 1 with delayed motor development, 4 were late onset GBS
      meningitis, 1 with normal results of neurologic examination, 3 were
      neurologically impaired with manifestations including delayed motor development
      (2 cases) and seizures (1 case). All the GBS strains were sensitive to penicillin
      and linezolid (13/13, 10/10), the susceptibility to levofloxacin, ampicillin and
      vancomycin were 11/12, 9/10, 8/13 respectively. CONCLUSION: The clinical
      manifestations of neonatal purulent meningitis caused by GBS are usually non
      specific. It is associated with long hospitalization, neurological impairments
      and sequelae. Monitoring of serum CRP level is valuable for early diagnosis.
      Antepartum prophylaxis, early diagnosis and therapy are vital. Large dose
      penicillin is the priority choice to treat the neonatal purulent meningitis
      caused by GBS, linezolid should be used in intractable cases.

PMID- 24739727
TI  - [Clinical analysis of nosocomial infection and risk factors of extremely
      premature infants].
AB  - OBJECTIVE: To investigate the incidence of nosocomial infections of extremely
      premature infants and to explore the risk factors and strategies for infection
      control. METHOD: There were 118 extremely premature infants who were confirmed to
      have nosocomial infection in neonatal intensive care unit of the authors'
      hospital from January 2008 to December 2012. Their data of the infection rate,
      risk factors and clinical characteristics were retrospectively analyzed. RESULT:
      During the study, nosocomial infection occurred in 78 extremely premature infants
      129 times. The nosocomial infection rate was 66.10%. The rate of ventilator
      associated pneumonia (VAP) was 1.43% (35/2 452). The catheter related blood
      stream infection (CRBSI) rate was 0.35% (16/4 613). There were 74 (57.36%) cases
      of pneumonia, which was the most common nosocomial infection of extremely
      premature infants. There were 35 cases of VAP, which accounted for 47.30% of
      pneumonia. The next was sepsis, 48 cases. Seventy-four (74/90, 82.22%) strains of
      isolates were Gram-negative bacteria, which accounted for the highest proportion,
      followed by Gram-positive (12 strains), fungus (4 strains); Klebsiella pneumonia
      is the most common pathogens of nosocomial infection in extremely premature
      infants. The isolation rates of Klebsiella pneumonia with positive extended
      spectrum beta-lactamases (ESBL) were 90.91% (20/22) , universally resistant to
      cephalosporins. Single-factor analysis showed that the body weight, mechanical
      ventilation, umbilical vein catheterization, central venous catheter, parenteral
      nutrition and hospitalization time were risk factors for nosocomial infections in
      extremely preterm infants. Logistic regression analysis showed that length of
      hospitalization (OR = 1.024, P = 0.043) and central venous catheterization (OR =
      6.170, P = 0.041) were independent risk factors of nosocomial infection.
      CONCLUSION: Extremely preterm infants were at higher risk of nosocomial
      infection. It is important to identify the high risk factors for nosocomial
      infections in extremely premature infants. To shorten time for mechanical
      ventilation, central venous catheterization and hospitalization days would be
      conducive to reducing the morbidity of nosocomial infection.

PMID- 24739728
TI  - [Analysis on diagnosis and treatment of 15 cases with severe influenza A].
AB  - OBJECTIVE: To analyze the diagnosis and treatment characteristics of patients
      with severe Influenza A. METHOD: A retrospective investigation on the clinical
      manifestation, chest radiography, electronic fiber bronchoscopy and the histology
      of the cast, rescue course and outcome was conducted in 15 children with severe
      influenza A during January to May of 2013. RESULT: Eleven cases were male, the
      range of age was 2 to 6 years; 5 cases were female, the range of age was 1 month
      to 6 years, accouting for 4.2% of hospitalized children with influenza. Three
      patients had an underlying chronic disease, two had nephrotic syndrome, and one
      had congenital heart disease. All the 15 cases were diagnosed as severe influenza
      A virus infection complicated with pneumonia and respiratory failure, of whom 10
      cases were infected with H1N1 virus , the other 5 cases could not be identified
      as H1N1 virus by using H1N1 kit, but none of the 15 cases were infected with H7N9
      virus. Of 15 cases, 8 had atelectasis, 4 had pneumothorax, 3 had
      pneumomediastinum, 4 had pleural effusion, 1 had pneumorrhagia; 12 patients
      required mechanical ventilation. 1 only required noninvasive mask CPAP, 2 did not
      require assisted ventilation, they were just given mask oxygen. Seven cases'
      sputum culture showed combined infection with bacteria and fungi, sputum smear
      examination detected: G(+) cocci in 2 cases, and G(-) bacilli in the other 2. By
      using electronic fiber bronchoscopy, bronchial cast was detected in 5 patiens.
      Histological examination of the bronchial cast revealed a fibrinous exudation
      containing large quantity of eosinophils, neutrophils in 1 patients, fibrinous
      exudation and necrotic material containing large quantity of neutrophils in 4
      patients. After the bronchial casts were removed, 4 patients were improved
      greatly. All patients were treated with postural drainage of left and right side
      position, massage of electric oscillation, strengthening the sputum suction
      aiming to improve pulmonary ventilation function. Three patients died: 1 case was
      compliicated with nephrotic syndrome, another case had congenital heart disease,
      and 1 case hads pneumorrhagia, renal failure and multiple organ dysfunction
      syndrome (MODS). CONCLUSION: The mortality of severe Influenza A is higher if it
      is complicated with underlying chronic diseases. In children undergoing rapid and
      progressive respiratory distress with lung atelectasis, consolidation or
      emphysema on chest X-ray, plastic bronchitis should be considered. Electronic
      fiber bronchoscopy should be performed early Lung physicotherapeutics still are
      important assistant measures for improving the pulmonary ventilation function.

PMID- 24739729
TI  - [The first case report of the implementation of transbronchial needle aspiration
      (TBNA) inmediastinal and hilar lymphadenopathy of a child in China].

PMID- 24739731
TI  - [Nutritional screening and assessment in critically ill children].

PMID- 24739730
TI  - [Value of N-terminal pro-brain natriuretic peptide in the early evaluation of
      cardiovasculardysfunction in critically ill children].

PMID- 24739732
TI  - [Advances in studies on mechanism of gastroesophageal reflux-induced cough].

PMID- 24739733
TI  - Umbilical cord tissue-derived mesenchymal stem cells induce apoptosis in PC-3
      prostate cancer cells through activation of JNK and downregulation of PI3K/AKT
      signaling.
AB  - INTRODUCTION: Although mesenchymal stem cells (MSCs) have antitumor potential in
      hepatocellular carcinoma and breast cancer cells, the antitumor mechanism of
      human umbilical cord mesenchymal stem cells (hUCMSCs) in prostate cancer cells
      still remains unclear. Thus, in the present study, we elucidated the antitumor
      activity of hUCMSCs in PC-3 prostate cancer cells in vitro and in vivo. METHODS:
      hUCMSCs were isolated from Wharton jelly of umbilical cord and characterized via
      induction of differentiations, osteogenesis, and adipogenesis. Antitumor effects
      of UCMSCs on tumor growth were evaluated in a co-culture condition with PC-3
      prostate cancer cells. PC-3 cells were subcutaneously (sc) injected into the left
      flank of nude mice, and UCMSCs were sc injected into the right flank of the same
      mouse. RESULTS: We found that hUCMSCs inhibited the proliferation of PC-3 cells
      in the co-culture condition. Furthermore, co-culture of hUCMSCs induced the
      cleavage of caspase 9/3 and PARP, activated c-jun NH2-terminal kinase (JNK), and
      Bax, and attenuated the phosphorylation of phosphatidylinositol 3-kinase (PI3K)/
      AKT, extracellular signal-regulated kinase (ERK), and the expression of survival
      genes such as Bcl-2, Bcl-xL, Survivin, Mcl-1, and cIAP-1 in PC-3 cells in Western
      blotting assay. Conversely, we found that treatment of specific JNK inhibitor
      SP600125 suppressed the cleavages of caspase 9/3 and PARP induced by hUCMSCs in
      PC-3 cells by Western blotting and immunofluorescence assay. The homing of
      hUCMSCs to, and TUNEL-positive cells on, the K562 xenograft tumor region were
      detected in Nu/nu-BALB/c mouse. CONCLUSIONS: These results suggest that UCMSCs
      inhibit tumor growth and have the antitumor potential for PC-3 prostate cancer
      treatment.

PMID- 24739734
TI  - Neurofibroma invading into urinary bladder presenting with symptoms of obstructed
      defecation and a large perineal hernia.
AB  - BACKGROUND: Pelvic floor hernias pose a diagnostic and a treatment challange.
      Neurofibromatosis is a rare systemic disease, and urinary tract involvement is
      rare. CASE PRESENTATION: Here we report a case of a 54-year-old female with
      multiple neurofibromatosis who presented with features of obstructed defecation
      and was found to have a large perineal hernia. At surgery, we found an unusual
      herniation of a large neuropathic bladder and rectum through a perineal defect.
      She underwent reduction cystoplasty and repair of the pelvic floor using a
      prolene mesh. Subsequent histopathological examination confirmed a large
      neurofibroma infiltrating the urinary bladder. CONCLUSION: Neurofibromatosis of
      the bladder is rare it should be considered as a differential diagnosis in
      patients presenting with symptoms of obstructed defecation.

PMID- 24739735
TI  - Psychometric characteristics of the postconcussion symptom inventory in children
      and adolescents.
AB  - Psychometric characteristics of the Postconcussion Symptom Inventory (PCSI) were
      examined in both concussed (n = 633) and uninjured (n = 1,273) 5 to 18 year olds.
      Parent- and self-report forms were created with developmentally appropriate
      wording and content. Factor analyses identified physical, cognitive, emotional,
      and sleep factors; that did not load strongly or discriminate between groups were
      eliminated. Internal consistency was strong for the total scales (alpha = 0.8
      0.9). Test-retest reliability for the self-report forms was moderate to strong
      (intraclass coeffecients, ICCs = 0.65-0.89). Parent and self-report concordance
      was moderate (r = .44-.65), underscoring the importance of both perspectives.
      Convergent validity with another symptom measure was good (r = .8).
      Classification analyses indicated greater discriminability from parent report,
      but caveats to this are presented. With strong psychometric characteristics, the
      four versions of the PCSI capture important postconcussion symptoms and can be
      utilized to track recovery from pediatric concussion and guide treatment
      recommendations. 

PMID- 24739736
TI  - Multi-scale structural and chemical analysis of sugarcane bagasse in the process
      of sequential acid-base pretreatment and ethanol production by Scheffersomyces
      shehatae and Saccharomyces cerevisiae.
AB  - BACKGROUND: Heavy usage of gasoline, burgeoning fuel prices, and environmental
      issues have paved the way for the exploration of cellulosic ethanol. Cellulosic
      ethanol production technologies are emerging and require continued technological
      advancements. One of the most challenging issues is the pretreatment of
      lignocellulosic biomass for the desired sugars yields after enzymatic hydrolysis.
      We hypothesized that consecutive dilute sulfuric acid-dilute sodium hydroxide
      pretreatment would overcome the native recalcitrance of sugarcane bagasse (SB) by
      enhancing cellulase accessibility of the embedded cellulosic microfibrils.
      RESULTS: SB hemicellulosic hydrolysate after concentration by vacuum evaporation
      and detoxification showed 30.89 g/l xylose along with other products (0.32 g/l
      glucose, 2.31 g/l arabinose, and 1.26 g/l acetic acid). The recovered cellulignin
      was subsequently delignified by sodium hydroxide mediated pretreatment. The acid
      base pretreated material released 48.50 g/l total reducing sugars (0.91 g
      sugars/g cellulose amount in SB) after enzymatic hydrolysis. Ultra-structural
      mapping of acid-base pretreated and enzyme hydrolyzed SB by microscopic analysis
      (scanning electron microcopy (SEM), transmitted light microscopy (TLM), and
      spectroscopic analysis (X-ray diffraction (XRD), Fourier transform infrared
      (FTIR) spectroscopy, Fourier transform near-infrared (FT-NIR) spectroscopy, and
      nuclear magnetic resonance (NMR) spectroscopy) elucidated the molecular changes
      in hemicellulose, cellulose, and lignin components of bagasse. The detoxified
      hemicellulosic hydrolysate was fermented by Scheffersomyces shehatae (syn.
      Candida shehatae UFMG HM 52.2) and resulted in 9.11 g/l ethanol production (yield
      0.38 g/g) after 48 hours of fermentation. Enzymatic hydrolysate when fermented by
      Saccharomyces cerevisiae 174 revealed 8.13 g/l ethanol (yield 0.22 g/g) after 72
      hours of fermentation. CONCLUSIONS: Multi-scale structural studies of SB after
      sequential acid-base pretreatment and enzymatic hydrolysis showed marked changes
      in hemicellulose and lignin removal at molecular level. The cellulosic material
      showed high saccharification efficiency after enzymatic hydrolysis.
      Hemicellulosic and cellulosic hydrolysates revealed moderate ethanol production
      by S. shehatae and S. cerevisiae under batch fermentation conditions.

PMID- 24739737
TI  - Gene expression: RNAi as a global transcriptional activator.

PMID- 24739738
TI  - Molecular motors: Hook-ing up early endosomes.

PMID- 24739739
TI  - Metabolism: YAP and TAZ under metabolic control.

PMID- 24739740
TI  - DEP domains: structurally similar but functionally different.
AB  - The Dishevelled, EGL-10 and pleckstrin (DEP) domain is a globular protein domain
      that is present in about ten human protein families with well-defined structural
      features. A picture is emerging that DEP domains mainly function in the spatial
      and temporal control of diverse signal transduction events by recruiting proteins
      to the plasma membrane. DEP domains can interact with various partners at the
      membrane, including phospholipids and membrane receptors, and their binding is
      subject to regulation. 

PMID- 24739741
TI  - Advances in whole-embryo imaging: a quantitative transition is underway.
AB  - With the advent of imaging probes and live microscopy, developmental biologists
      have markedly extended our understanding of the molecular and cellular details of
      embryonic development. To fully comprehend the complex mechanistic framework that
      forms the developing organism, quantitative studies with high fidelity in space
      and time are now required. We discuss how integrating established, newly
      introduced and future imaging tools with quantitative analysis will ensure that
      imaging can fulfil its promise to elucidate how new life begins. 

PMID- 24739742
TI  - Non-healing old world cutaneous leishmaniasis caused by L. infantum in a patient
      from Spain.
AB  - BACKGROUND: The prevalence of Old World Cutaneous Leishmaniasis in the
      Mediterranean region is increasing and in Southern Europe often caused by
      Leishmania infantum. Spontaneous healing of cutaneous leishmaniasis is commonly
      observed, especially if caused by L. major, whereas L. infantum associated
      lesions have been reported with longer disease duration and decreased tendency
      for self-limitation, however, available information is sparse. CASE PRESENTATION:
      We report the case of an otherwise healthy woman from Southern Spain who
      presented with a seven years persistent, non-healing, painless, central
      ulcerated, nodular cutaneous lesion with a diameter of 2 cm of the forearm.
      Cutaneous leishmaniasis was diagnosed by smear and histology, showing large
      amounts of leishmania amastigotes in subepidermal histiocytes and extensive
      lymphocyte and plasma cell inflammation. L. infantum as the causative pathogen
      was confirmed by restriction fragment length polymorphism and microsatellite-PCR.
      Systemic or visceral involvement was excluded by negative leishmania serology and
      clinical presentation, relevant concomitant diseases or immunosuppression were
      excluded including quantification of immunoglobulin levels and lymphocyte
      phenotyping. Topical and systemic anti-infectious treatment options, often
      limited in terms of efficacy, tolerability and long lasting treatment duration,
      were considered. Treatment was successfully performed by surgical extraction in
      local anaesthesia only. CONCLUSION: To our knowledge this is the longest reported
      duration of a L. infantum associated cutaneous leishmaniasis indicating a
      potential long lasting natural evolution of the disease in an otherwise healthy
      and immunocompetent patient, however, high parasite density may have reflected a
      lack of a L. infantum specific immune response. Complete surgical extraction can
      be successfully performed as treatment.

PMID- 24739744
TI  - Using the elliptical excision technique for double upper lip management.

PMID- 24739743
TI  - Allergic sensitization: screening methods.
AB  - Experimental in silico, in vitro, and rodent models for screening and predicting
      protein sensitizing potential are discussed, including whether there is evidence
      of new sensitizations and allergies since the introduction of genetically
      modified crops in 1996, the importance of linear versus conformational epitopes,
      and protein families that become allergens. Some common challenges for predicting
      protein sensitization are addressed: (a) exposure routes; (b) frequency and dose
      of exposure; (c) dose-response relationships; (d) role of digestion, food
      processing, and the food matrix; (e) role of infection; (f) role of the gut
      microbiota; (g) influence of the structure and physicochemical properties of the
      protein; and (h) the genetic background and physiology of consumers. The
      consensus view is that sensitization screening models are not yet validated to
      definitively predict the de novo sensitizing potential of a novel protein.
      However, they would be extremely useful in the discovery and research phases of
      understanding the mechanisms of food allergy development, and may prove fruitful
      to provide information regarding potential allergenicity risk assessment of
      future products on a case by case basis. These data and findings were presented
      at a 2012 international symposium in Prague organized by the Protein
      Allergenicity Technical Committee of the International Life Sciences Institute's
      Health and Environmental Sciences Institute. 

PMID- 24739745
TI  - Preventing hair interference during ear surgery.

PMID- 24739746
TI  - Internal maxillary artery pseudoaneurysm subsequent gunshot wound in a teenager.

PMID- 24739748
TI  - Bilateral osteoma of the maxillary sinus or anatomic variation?

PMID- 24739749
TI  - Temporomandibular synovial chondromatosis with numerous nodules.
AB  - Synovial chondromatosis of the temporomandibular joint is an uncommon disorder
      with an indolent clinical course and a slow progression. We report a rare case of
      unilateral early synovial chondromatosis of the temporomandibular joint with
      numerous nodules and discuss possible etiologies for the entity of loose bodies
      and the evolution of this disease. 

PMID- 24739750
TI  - Treatment of unilateral mandibular angle fracture by closed reduction.

PMID- 24739751
TI  - Subcutaneous fibrolipoma of the pubic area.

PMID- 24739752
TI  - Clinical outcomes of endoscopic and open resection of recurrent sinonasal
      inverted papilloma.
AB  - PURPOSE: The aim of this study was to investigate the effectiveness of endoscopic
      surgery for recurrent sinonasal inverted papilloma and evaluate the recurrence
      rates of endoscopic and open resection at a single institution. METHODS: This
      retrospective study was performed on 21 patients with histopathologically
      confirmed recurrent sinonasal inverted papilloma who underwent an operation in
      our department from January 1990 to January 2005. The 21 recurrent cases were
      categorized according to the Krouse staging system into 1 case of stage 1 (5%),
      18 cases of stage 2 (85%), 2 cases of stage 3 (10%), and 0 cases of stage 4 (0%).
      There were 7 patients (33%) who underwent endoscopic resection and 14 patients
      (67%) who underwent open resection. RESULTS: Of the 21 recurrent patients who
      underwent resection, 4 patients (19%) were found to have recurrence. The mean
      time to recurrence was 28 months. The recurrence rates of the patients with stage
      1, stage 2, and stage 3 were 0%, 17%, and 50%, respectively (P < 0.05).
      Recurrence was observed in 1 patient (14%) in the endoscopic group and 3 patients
      (21%) in the open group (P > 0.05). There was statistical difference in
      recurrence rates between stage 1 and stage 2 in the endoscopic group (P < 0.05)
      and between stage 2 and stage 3 in the open group (P < 0.05). There was no
      significant difference in recurrence rates between the endoscopic and the open
      group in stage 2 (P > 0.05). CONCLUSIONS: Endoscopic and open approaches are both
      available to achieve radical excision of the recurrent sinonasal inverted
      papilloma, with similar rates of recurrence. The risk for recurrence is likely
      related to the Krouse stage of the tumor, with more aggressive tumors having a
      higher propensity for recurrence. Endoscopic surgery is an effective treatment of
      recurrent sinonasal inverted papilloma.

PMID- 24739753
TI  - Osseous reconstruction using an occlusive titanium membrane following marginal
      mandibulectomy: proof of principle.
AB  - Guided bone regeneration using barrier membranes is useful in bone augmentation.
      In contrast to flexible membranes, stiff membranes such as titanium membranes are
      capable of maintaining sufficient space underneath them. We report a case of bone
      regeneration under an occlusive titanium membrane following marginal
      mandibulectomy in a 50-year-old patient with odontogenic keratocyst. Preoperative
      analysis of the anatomical conditions was evaluated with panoramic radiographs
      and spiral computer tomography (CT) scan. The digital data from the CT scan were
      transferred to a personal computer. Using Simplant software, a mirror image of
      the right mandible was constructed from which a custom-made titanium membrane was
      made. The cyst with the remaining inferior alveolar nerve was removed and
      curettage of the lesion was performed under general anesthesia. The definitive
      titanium plate was inserted and fixated with osteosynthesis screws, and then
      removed 5 years later. Postoperative CT scanning showed good healing, bone growth
      under the titanium plate, and no evidence of residual cyst The titanium plate
      reinforced the mandibular skeleton and restored the shape of the mandible and
      facial symmetry; it also promoted new bone formation to fill in the mandibular
      defects. 

PMID- 24739754
TI  - "Implant surgery triggered" bisphosphonate-related osteonecrosis of the jaws
      (BRONJ).

PMID- 24739755
TI  - Closed management by Ginestet hook elevator of V-shaped fractures of the
      zygomatic arch.

PMID- 24739756
TI  - Active skepticism: beyond the IOM's CTSA report.

PMID- 24739757
TI  - Manufacturing challenges in regenerative medicine.
AB  - Along with scientific and regulatory issues, the translation of cell and tissue
      therapies in the routine clinical practice needs to address standardization and
      cost-effectiveness through the definition of suitable manufacturing paradigms. 

PMID- 24739758
TI  - FibronectinEDA promotes chronic cutaneous fibrosis through Toll-like receptor
      signaling.
AB  - Scleroderma is a progressive autoimmune disease affecting multiple organs.
      Fibrosis, the hallmark of scleroderma, represents transformation of self-limited
      wound healing into a deregulated self-sustaining process. The factors responsible
      for maintaining persistent fibroblast activation in scleroderma and other
      conditions with chronic fibrosis are not well understood. Toll-like receptor 4
      (TLR4) and its damage-associated endogenous ligands are implicated in immune and
      fibrotic responses. We now show that fibronectin extra domain A (Fn(EDA)) is an
      endogenous TLR4 ligand markedly elevated in the circulation and lesional skin
      biopsies from patients with scleroderma, as well as in mice with experimentally
      induced cutaneous fibrosis. Synthesis of Fn(EDA) was preferentially stimulated by
      transforming growth factor-beta in normal fibroblasts and was constitutively up
      regulated in scleroderma fibroblasts. Exogenous Fn(EDA) was a potent stimulus for
      collagen production, myofibroblast differentiation, and wound healing in vitro
      and increased the mechanical stiffness of human organotypic skin equivalents.
      Each of these profibrotic Fn(EDA) responses was abrogated by genetic, RNA
      interference, or pharmacological disruption of TLR4 signaling. Moreover, either
      genetic loss of Fn(EDA) or TLR4 blockade using a small molecule mitigated
      experimentally induced cutaneous fibrosis in mice. These observations implicate
      the Fn(EDA)-TLR4 axis in cutaneous fibrosis and suggest a paradigm in which
      aberrant Fn(EDA) accumulation in the fibrotic milieu drives sustained fibroblast
      activation via TLR4. This model explains how a damage-associated endogenous TLR4
      ligand might contribute to converting self-limited tissue repair responses into
      intractable fibrogenesis in chronic conditions such as scleroderma. Disrupting
      sustained TLR4 signaling therefore represents a potential strategy for the
      treatment of fibrosis in scleroderma. 

PMID- 24739760
TI  - An orally available, small-molecule polymerase inhibitor shows efficacy against a
      lethal morbillivirus infection in a large animal model.
AB  - Measles virus is a highly infectious morbillivirus responsible for major
      morbidity and mortality in unvaccinated humans. The related, zoonotic canine
      distemper virus (CDV) induces morbillivirus disease in ferrets with 100%
      lethality. We report an orally available, shelf-stable pan-morbillivirus
      inhibitor that targets the viral RNA polymerase. Prophylactic oral treatment of
      ferrets infected intranasally with a lethal CDV dose reduced viremia and
      prolonged survival. Ferrets infected with the same dose of virus that received
      post-infection treatment at the onset of viremia showed low-grade viral loads,
      remained asymptomatic, and recovered from infection, whereas control animals
      succumbed to the disease. Animals that recovered also mounted a robust immune
      response and were protected against rechallenge with a lethal CDV dose. Drug
      resistant viral recombinants were generated and found to be attenuated and
      transmission-impaired compared to the genetic parent virus. These findings may
      pioneer a path toward an effective morbillivirus therapy that could aid measles
      eradication by synergizing with vaccination to close gaps in herd immunity due to
      vaccine refusal. 

PMID- 24739759
TI  - Induction of antigen-specific immunity with a vaccine targeting NY-ESO-1 to the
      dendritic cell receptor DEC-205.
AB  - Immune-based therapies for cancer are generating substantial interest because of
      the success of immune checkpoint inhibitors. This study aimed to enhance
      anticancer immunity by exploiting the capacity of dendritic cells (DCs) to
      initiate T cell immunity by efficient uptake and presentation of endocytosed
      material. Delivery of tumor-associated antigens to DCs using receptor-specific
      monoclonal antibodies (mAbs) in the presence of DC-activating agents elicits
      robust antigen-specific immune responses in preclinical models. DEC-205 (CD205),
      a molecule expressed on DCs, has been extensively studied for its role in antigen
      processing and presentation. CDX-1401 is a vaccine composed of a human mAb
      specific for DEC-205 fused to the full-length tumor antigen NY-ESO-1. This phase
      1 trial assessed the safety, immunogenicity, and clinical activity of escalating
      doses of CDX-1401 with the Toll-like receptor (TLR) agonists resiquimod (TLR7/8)
      and Hiltonol (poly-ICLC, TLR3) in 45 patients with advanced malignancies
      refractory to available therapies. Treatment induced humoral and cellular
      immunity to NY-ESO-1 in patients with confirmed NY-ESO-1-expressing tumors across
      various dose levels and adjuvant combinations. No dose-limiting or grade 3
      toxicities were reported. Thirteen patients experienced stabilization of disease,
      with a median duration of 6.7 months (range, 2.4+ to 13.4 months). Two patients
      had tumor regression (~20% shrinkage in target lesions). Six of eight patients
      who received immune-checkpoint inhibitors within 3 months after CDX-1401
      administration had objective tumor regression. This first-in-human study of a
      protein vaccine targeting DCs demonstrates its feasibility, safety, and
      biological activity and provides rationale for combination immunotherapy
      strategies including immune checkpoint blockade. 

PMID- 24739761
TI  - Food expenditure patterns in the Canadian Arctic show cause for concern for
      obesity and chronic disease.
AB  - BACKGROUND: Little is understood about the economic factors that have influenced
      the nutrition transition from traditional to store-bought foods that are
      typically high in fat and sugar amongst people living in the Canadian Arctic.
      This study aims to determine the pattern of household food expenditure in the
      Canadian Arctic. METHOD: Local food prices were collected over 12 months in six
      communities in Nunavut and the Northwest Territories. Dietary intake data were
      collected from 441 adults using a validated quantitative food frequency
      questionnaire. Money spent on six food groups was calculated along with the cost
      of energy and selected nutrients per person. RESULTS: Participants spent
      approximately 10% of total food expenditure on each of the food groups of
      fruit/vegetables, grains and potatoes, and dairy, 17% on traditional meats (e.g.
      caribou, goose, char, and seal liver), and 20% on non-traditional meats (e.g.
      beef, pork, chicken, fish, and processed meats). Non-nutrient-dense foods (NNDF)
      accounted for 34% of food expenditure. Younger participants (<30 years) spent
      more on NNDF and less on traditional meats compared with the older age groups.
      Participants with higher levels of formal education spent more on fruit and
      vegetables and less on traditional meats, when compared with participants with
      lower levels of formal education. CONCLUSIONS: Participants spent most household
      income on NNDF, a possible consequence of generation discrepancy between younger
      and older participants. The tendency toward NNDF, particularly among youth,
      should be addressed with an assessment of predictive factors and the development
      of targeted approaches to population-based interventions.

PMID- 24739762
TI  - Dermoscopy as an adjuvant tool for detecting skin leiomyomas in patient with
      uterine fibroids and cerebral cavernomas.
AB  - BACKGROUND: Hereditary syndromes frequently need the cooperation of different
      specialties to increase diagnostic competence. Multiple cutaneous and uterine
      leiomyomatosis syndrome is a rare autosomal dominant disorder caused by the
      mutations of the fumarate hydratase gene, demonstrated in 80 to 100 percent of
      affected individuals. This can be linked to an increased risk of renal cancer in
      both sexes. The skin involvement is described to highlight the diagnostic role of
      the cutaneous counterpart in identifying this rare syndrome. CASE PRESENTATION: A
      37-year-old woman suffering from several uterine fibroids presented multiple,
      painful, papulo-nodules on her left subscapular side, both forearms and legs. The
      patient underwent surgery on six lesions: five were leiomyomas, whilst one was a
      dermatofibroma. Genetic sequencing did not evidence known fumarate hydratase gene
      mutations. Dermoscopy showed a brown delicate pigmented network and included
      leiomyomas among the non-melanocytic benign skin tumours featuring a
      dermatofibroma-like pattern. Abdominal computerized-tomography scan did not
      reveal renal cancer, but brain magnetic resonance imaging showed one asymptomatic
      cerebral cavernoma. The patient benefited from the surgical removal of the five
      larger cutaneous lesions and from gabapentin, which relieved her pain.
      CONCLUSIONS: This observation highlights the usefulness of dermoscopy in the
      diagnosis of cutaneous leiomyomas disclosing multiple cutaneous and uterine
      leiomyomatosis syndrome. Dermoscopy should be performed for non-melanocytic
      multiple lesions mimicking leiomyomas in a large number of patients, to establish
      a strict classification and identify false negative cases or evaluate them as
      dermatofibromas. In this case, the dermatologist recognized the risk of renal
      cancer and cerebral cavernomas.

PMID- 24739763
TI  - Increased range of motion and decreased strength of the thumb in massage
      practitioners with thumb pain.
AB  - The purpose of this study was to compare the range of motion (ROM) and strength
      of the metacarpophalangeal (MP) and interphalangeal (IP) joints among massage
      practitioners with and without thumb pain and control subjects. Sixteen massage
      practitioners with thumb pain, 16 practitioners without thumb pain, and 16
      control subjects participated in this study. ROM of flexion, extension, and
      abduction in the MP joint; ROM of flexion and extension in the IP joint of the
      thumb; strength of the flexor pollicis brevis (FPB), extensor pollicis brevis
      (EPB), abductor pollicis brevis, flexor pollicis longus (FPL), and extensor
      pollicis longus measured in all subjects. ROM of extension and abduction in the
      MP joint were significantly increased in massage practitioners with and without
      thumb pain compared with control subjects. ROM of extension in the IP joint was
      significantly increased in massage practitioners with thumb pain compared with
      those without thumb pain. The strength of the EPB and FPL muscle was
      significantly decreased in massage practitioners with thumb pain compared with
      those without thumb pain and control subjects, respectively. In addition, there
      was significantly increased EPB/FPB strength in massage practitioners without
      thumb pain compared to those with thumb pain and control subjects. 

PMID- 24739764
TI  - A cross sectional study on hand-arm vibration syndrome among a group of tree
      fellers in a tropical environment.
AB  - This study aimed to explore the clinical characteristics of hand arm vibration
      syndrome (HAVS) in a group of tree fellers in a tropical environment. We examined
      all tree fellers and selected control subjects in a logging camp of central
      Sarawak for vibration exposure and presence of HAVS symptoms utilizing
      vibrotactile perception threshold test (VPT) and cold water provocation test
      (CWP). None of the subjects reported white finger. The tree fellers reported
      significantly higher prevalence of finger coldness as compared to the control
      subjects (OR=10.32, 95%CI=1.21-87.94). A lower finger skin temperature, longer
      fingernail capillary return time and higher VPT were observed among the tree
      fellers as compared to the control subjects in all fingers (effect size >0.5).
      The VPT following CWP of the tree fellers was significantly higher (repeated
      measures ANOVA p=0.002, partial eta(2)=0.196) than the control subject. The A (8)
      level was associated with finger tingling, numbness and dullness (effect
      size=0.983) and finger coldness (effect size=0.524) among the tree fellers.
      Finger coldness and finger tingling, numbness and dullness are important symptoms
      for HAVS in tropical environment that may indicate vascular and neurological
      damage due to hand-transmitted vibration exposure. 

PMID- 24739765
TI  - Applying the Taguchi method to river water pollution remediation strategy
      optimization.
AB  - Optimization methods usually obtain the travel direction of the solution by
      substituting the solutions into the objective function. However, if the solution
      space is too large, this search method may be time consuming. In order to address
      this problem, this study incorporated the Taguchi method into the solution space
      search process of the optimization method, and used the characteristics of the
      Taguchi method to sequence the effects of the variation of decision variables on
      the system. Based on the level of effect, this study determined the impact factor
      of decision variables and the optimal solution for the model. The integration of
      the Taguchi method and the solution optimization method successfully obtained the
      optimal solution of the optimization problem, while significantly reducing the
      solution computing time and enhancing the river water quality. The results
      suggested that the basin with the greatest water quality improvement
      effectiveness is the Dahan River. Under the optimal strategy of this study, the
      severe pollution length was reduced from 18 km to 5 km. 

PMID- 24739766
TI  - Resiliency training in Indian children: a pilot investigation of the Penn
      Resiliency Program.
AB  - This paper examines the effectiveness of the Penn Resiliency Program (PRP) in an
      urban Indian setting. The PRP is a program to prevent depression in early
      adolescence and has proved successful in changing children's attributional style
      of life events. While the program has been successful in preventing symptoms of
      depression in Western populations, the current study explored whether this
      program could be effective with an Indian sample. The aim of the current study
      was twofold; first, to study the attributional style of early adolescents in
      India and identify negative effects (if any) and second, to gain insights in
      using the PRP as a tool to change explanatory styles in Indian children. A total
      of 58 children participated in the study (Intervention group n = 29 and Control
      group n = 29). An Analysis of Covariance comparing post-test scores on Children's
      Attributional Style Questionnaire (CASQ) while controlling for baseline scores
      indicated that children in the intervention group exhibited a significant
      reduction in pessimistic explanatory style and an increase in optimistic
      orientation compared to children in the control group. This indicates that the
      program was effective in changing negative attribution styles among upper-class
      Indian school children. Future work may look into the longer impact of the
      program as well as further considerations into adapting the program for a middle
      class population. 

PMID- 24739767
TI  - Social cost of leptospirosis cases attributed to the 2011 disaster striking Nova
      Friburgo, Brazil.
AB  - The aim of this study was to estimate the social cost of the leptospirosis cases
      that were attributed to the natural disaster of January 2011 in Nova Friburgo
      (State of Rio de Janeiro, Brazil) through a partial economic assessment. This
      study utilized secondary data supplied by the Municipal Health Foundation of Nova
      Friburgo. Income scenarios based on the national and state minimum wages and on
      average income of the local population were employed. The total social cost of
      leptospirosis cases attributed to the 2011 disaster may range between US$21,500
      and US$66,000 for the lower income scenario and between US$23,900 and US$100,800
      for that of higher income. Empirical therapy represented a total avoided cost of
      US$14,800, in addition to a reduction in lethality. An estimated 31 deaths were
      avoided among confirmed cases of the disease, and no deaths resulted from the
      leptospirosis cases attributed to the natural disaster. There has been a
      significant post-disaster rise in leptospirosis incidence in the municipality,
      which illustrates the potential for increased cases--and hence costs--of this
      illness following natural disasters, which justifies the adoption of preventive
      measures in environmental health.

PMID- 24739768
TI  - Managing terrorism or accidental nuclear errors, preparing for iodine-131
      emergencies: a comprehensive review.
AB  - Chernobyl demonstrated that iodine-131 (131I) released in a nuclear accident can
      cause malignant thyroid nodules to develop in children within a 300 mile radius
      of the incident. Timely potassium iodide (KI) administration can prevent the
      development of thyroid cancer and the American Thyroid Association (ATA) and a
      number of United States governmental agencies recommend KI prophylaxis. Current
      pre-distribution of KI by the United States government and other governments with
      nuclear reactors is probably ineffective. Thus we undertook a thorough scientific
      review, regarding emergency response to 131I exposures. We propose: (1) pre
      distribution of KI to at risk populations; (2) prompt administration, within 2
      hours of the incident; (3) utilization of a lowest effective KI dose; (4)
      distribution extension to at least 300 miles from the epicenter of a potential
      nuclear incident; (5) education of the public about dietary iodide sources; (6)
      continued post-hoc analysis of the long-term impact of nuclear accidents; and (7)
      support for global iodine sufficiency programs. Approximately two billion people
      are at risk for iodine deficiency disorder (IDD), the world's leading cause of
      preventable brain damage. Iodide deficient individuals are at greater risk of
      developing thyroid cancer after 131I exposure. There are virtually no studies of
      KI prophylaxis in infants, children and adolescents, our target population.
      Because of their sensitivity to these side effects, we have suggested that we
      should extrapolate from the lowest effective adult dose, 15-30 mg or 1-2 mg per
      10 pounds for children. We encourage global health agencies (private and
      governmental) to consider these critical recommendations. 

PMID- 24739769
TI  - Japanese encephalitis risk and contextual risk factors in southwest China: a
      Bayesian hierarchical spatial and spatiotemporal analysis.
AB  - It is valuable to study the spatiotemporal pattern of Japanese encephalitis (JE)
      and its association with the contextual risk factors in southwest China, which is
      the most endemic area in China. Using data from 2004 to 2009, we applied
      GISmapping and spatial autocorrelation analysis to analyze reported incidence
      data of JE in 438 counties in southwest China, finding that JE cases were not
      randomly distributed, and a Bayesian hierarchical spatiotemporal model identified
      the east part of southwest China as a high risk area. Meanwhile, the Bayesian
      hierarchical spatial model in 2006 demonstrated a statistically significant
      association between JE and the agricultural and climatic variables, including the
      proportion of rural population, the pig-to-human ratio, the monthly precipitation
      and the monthly mean minimum and maximum temperatures. Particular emphasis was
      placed on the time-lagged effect for climatic factors. The regression method and
      the Spearman correlation analysis both identified a two-month lag for the
      precipitation, while the regression method found a one-month lag for temperature.
      The results show that the high risk area in the east part of southwest China may
      be connected to the agricultural and climatic factors. The routine surveillance
      and the allocation of health resources should be given more attention in this
      area. Moreover, the meteorological variables might be considered as possible
      predictors of JE in southwest China. 

PMID- 24739771
TI  - Paradox of health care in the world's greatest nation: commentary on the 2013
      Annual American Public Health Association Conference in Boston.

PMID- 24739770
TI  - Modifying health behavior to prevent cardiovascular diseases: a nationwide survey
      among German primary care physicians.
AB  - Cardiovascular diseases (CVD) are a major public health concern as they are the
      leading cause of death in developed countries. Primary care is considered to be
      the ideal setting for CVD prevention. Therefore, more than 4,000 German primary
      care physicians (PCPs) were asked about their attitudes towards and their
      activities regarding the prevention of CVD in the nationwide ASP-kardio Study.
      The focus of the study was on health behavior modification. Two thirds of the
      participating PCPs stated that they routinely provided brief inventions to assist
      patients in reducing both their tobacco (72%) and alcohol (61%) consumption, to
      encourage them to increase their levels of physical activity (72%), and to assist
      them in adjusting to a more healthy diet (66%), and in achieving a healthy body
      weight (69%). However, only between 23% (quitting smoking) and 49% (diet
      modification) of PCPs felt that they had been successful in helping patients
      modify their lifestyles. Insufficient reimbursement, cultural diversity and a
      lack of time were reported to be the most problematic barriers to successful
      intervention in the primary care setting. Despite these obstacles, the majority
      of German PCPs was engaged in prevention and health behavior intervention to
      reduce the incidence and progression of CVD. 

PMID- 24739772
TI  - On the road to prevention: road injury and health promotion.
AB  - Road traffic injuries are already the leading cause of injury mortality and
      morbidity globally and by 2030 are predicted to be the fifth leading cause of
      mortality in the world. Australia has seen a dramatic reduction in road deaths
      and serious injuries since the 1970s and holds an international reputation for
      road traffic injury prevention due, in part, to its success in pioneering the
      multidisciplinary and intersectoral approach needed to address this significant
      issue and by applying an evidence-led approach to policy development. The paper
      will discuss Australia's early success in road traffic injury prevention (road
      safety), particularly the achievements following the implementation of targeted
      programs that focussed on road user behaviours for which health promotion played
      a role. The most successful of these programs was the introduction of
      comprehensive seat belt laws, random breath testing and more recently, strategic
      speed enforcement programs. Amid an array of significant challenges faced by the
      transport system in the future, the rapid development in information and
      communication technologies applied to transport is likely to provide the next
      generation of road safety benefits. The potential for a semi-autonomous transport
      system is likely to provide the next significant decline in road fatalities and
      serious injuries over the next 2 decades and the role of health promotion in
      relation to raising community engagement and building coalitions to increase
      uptake of new technologies will be discussed. 

PMID- 24739773
TI  - From evidence to action: health promotion and alcohol.
AB  - Preventing alcohol-related harm presents a range of challenges including those
      related to political will, competing interests with disproportionate resources,
      and embedded drinking cultures. On the other hand there are opportunities for
      health promotion, including clear evidence on both the extent of the problem and
      evidence-based responses and growing community support for action. Australian
      researchers continue to contribute substantially to the international evidence
      base on alcohol, generating evidence for translation into effective programs and
      producing policy-relevant research on which action and advocacy can be based.
      Successes in other public health areas also provide useful models for public
      health approaches to alcohol. Those engaged in health promotion have often been
      required to do a lot with a little, including communicating health messages on a
      range of themes, countering industry activities that are contrary to good public
      health and involvement in policy development. Coalition approaches to alcohol
      related harm, including links with groups outside health, have recently gained
      momentum and show much potential. Alcohol issues are now firmly on the agenda of
      the public and decision-makers, and the alcohol industry has expressed clear
      concern at current levels of activity. This paper will consider briefly the
      nature of the challenge; evidence-based approaches; achievements and developments
      thus far; challenges and obstacles; and the role of health promotion and the
      health promotion workforce. 

PMID- 24739774
TI  - Urban design and health: progress to date and future challenges.
AB  - Over the last 15 years, a growing body of Australian and international evidence
      has demonstrated that urban design attributes are associated with a range of
      health outcomes. For example, the location of employment, shops and services,
      provision of public and active transport infrastructure and access to open space
      and recreational opportunities are associated with chronic disease risk factors
      such as physical activity levels, access to healthy food, social connectedness,
      and air quality. Despite the growing knowledge base, this evidence is not being
      consistently translated into urban planning policy and practice in Australia. Low
      density neighbourhoods with poor access to public transport, shops and services
      continue to be developed at a rapid rate in the sprawling outer suburbs of
      Australian cities. This paper provides an overview of the evidence of the
      association between the built environment and chronic diseases, highlighting
      progress and future challenges for health promotion. It argues that health
      promotion practitioners and researchers need to more closely engage with urban
      planning practitioners, policymakers and researchers to encourage the creation of
      healthy urban environments through integrated transport, land use and
      infrastructure planning. There is also a need for innovative research to evaluate
      the effectiveness of policy options. This would help evidence to be more
      effectively translated into policy and practice, making Australia a leader in
      planning healthy communities. 

PMID- 24739775
TI  - Health promotion: an ethical analysis.
AB  - Thinking and practising ethically requires reasoning systematically about the
      right thing to do. Health promotion ethics - a form of applied ethics - includes
      analysis of health promotion practice and how this can be ethically justified.
      Existing frameworks can assist in such evaluation. These acknowledge the moral
      value of delivering benefits. But benefits need to be weighed against burdens,
      harms or wrongs, and these should be minimised: they include invading privacy,
      breaking confidentiality, restraining liberty, undermining self-determination or
      people's own values, or perpetuating injustice. Thinking about the ethics of
      health promotion also means recognising health promotion as a normative ideal: a
      vision of the good society. This ideal society values health, sees citizens as
      active and includes them in decisions that affect them, and makes the state
      responsible for providing all of its citizens, no matter how advantaged or
      disadvantaged, with the conditions and resources they need to be healthy.
      Ethicists writing about health promotion have focused on this relationship
      between the citizen and the state. Comparing existing frameworks, theories and
      the expressed values of practitioners themselves, we can see common patterns. All
      oppose pursuing an instrumental, individualistic, health-at-all-costs vision of
      health promotion. And all defend the moral significance of just processes: those
      that engage with citizens in a transparent, inclusive and open way. In recent
      years, some Australian governments have sought to delegitimise health promotion,
      defining it as extraneous to the role of the state. Good evidence is not enough
      to counter this trend, because it is founded in competing visions of a good
      society. For this reason, the most pressing agenda for health promotion ethics is
      to engage with communities, in a procedurally just way, about the role and
      responsibilities of the citizen and the state in promoting and maintaining good
      health. 

PMID- 24739776
TI  - Getting Australia more active: challenges and opportunities for health promotion.
AB  - A growing body of evidence demonstrates that regular physical activity promotes
      health and assists in the prevention of non-communicable diseases but this is
      presently curtailed by low and unhealthy participation rates in Australia and
      comparable industrialised countries. Compounding the problem is knowledge that
      physical inactivity is independently associated with poor health outcomes.
      Despite physical activity being described as public health's 'best bet' or 'best
      buy', motivating individuals and groups to adopt and maintain physical activity
      continues to be a major challenge for health professionals. Global advocacy for
      prevention efforts must be operationalised through national to local strategies
      to promote and support physical activity in multiple settings including the home,
      schools and workplace. The Australian health promotion community has and
      continues to play a leadership role in physical activity promotion. However,
      there is an urgent need to continue to promote the importance of physical
      activity, along with its pivotal role in the prevention of non-communicable
      diseases, alongside related agendas including healthy diets, tobacco control and
      environmental sustainability. This commentary overviews the contemporary status
      of physical activity promotion in Australia and identifies key challenges and
      opportunities moving forward. 

PMID- 24739777
TI  - Mobilisation, politics, investment and constant adaptation: lessons from the
      Australian health-promotion response to HIV.
AB  - ISSUE ADDRESSED: The Australian response to HIV oversaw one of the most rapid and
      sustained changes in community behaviour in Australia's health-promotion history.
      The combined action of communities of gay men, sex workers, people who inject
      drugs, people living with HIV and clinicians working in partnership with
      government, public health and research has been recognised for many years as
      highly successful in minimising the HIV epidemic. METHODS: This article will show
      how the Australian HIV partnership response moved from a crisis response to a
      constant and continuously adapting response, with challenges in sustaining the
      partnership. Drawing on key themes, lessons for broader health promotion are
      identified. RESULTS: The Australian HIV response has shown that a partnership
      that is engaged, politically active, adaptive and resourced to work across
      multiple social, structural, behavioural and health-service levels can reduce the
      transmission and impact of HIV. CONCLUSIONS: The experience of the response to
      HIV, including its successes and failures, has lessons applicable across health
      promotion. This includes the need to harness community mobilisation and action;
      sustain participation, investment and leadership across the partnership; commit
      to social, political and structural approaches; and build and use evidence from
      multiple sources to continuously adapt and evolve. So what? The Australian HIV
      response was one of the first health issues to have the Ottawa Charter embedded
      from the beginning, and has many lessons to offer broader health promotion and
      common challenges. As a profession and a movement, health promotion needs to
      engage with the interactions and synergies across the promotion of health, learn
      from our evidence, and resist the siloing of our responses.

PMID- 24739778
TI  - Reflections on the framing of 'health equity' in the National Primary Health Care
      Strategic Framework: a cause for celebration or concern?
AB  - ISSUE ADDRESSED: There has been a growing national and global focus on the need
      to address social determinants of health to better achieve equitable health
      outcomes. In Australia, this focus is now being embedded into state, territory
      and Commonwealth government health policies. In this paper I use the National
      Primary Health Care Strategic Framework as a case study to examine the way in
      which 'health equity' and other related terms have been framed within a current
      national health policy context. DISCUSSION: Using a critically reflective
      approach, I argue that primary health care and health promotion professionals
      need to capitalise on the inclusion of terms such as 'action on social
      determinants of health', 'health equity' and 'reducing inequity' through emerging
      national health policies, such as the National Primary Health Care Strategic
      Framework. Yet, there is also a need to proceed with caution. The way in which
      these terms are framed appears to deviate from the principles, values and
      ideologies on which they are historically based. The implications for
      contemporary health promotion practice in Australia are discussed. CONCLUSIONS:
      Primary health care and health promotion professionals working in both policy and
      practice contexts are encouraged to engage in critical reflective practice when
      interpreting and considering the implementation requirements of national health
      policies that incorporate a health equity focus. So what? To build health equity
      in Australia, primary health care and health promotion professionals will be
      required to engage in the skilful reframing of current primary health care policy
      discourses relating to health equity during health promotion planning,
      implementation and evaluation processes.

PMID- 24739779
TI  - Knowledge, attitudes and beliefs about lung cancer in three culturally and
      linguistically diverse communities living in Australia: a qualitative study.
AB  - ISSUE ADDRESSED: Knowledge, attitudes and beliefs about lung cancer among
      Chinese, Vietnamese and Arabic-speaking communities in Sydney, New South Wales
      (NSW) are explored. METHODS: Seven focus groups were completed with a total of 51
      participants (smokers and non-smokers) from three culturally and linguistically
      diverse communities (CALD). Five topics were discussed and translated summaries
      from focus groups were thematically analysed. RESULTS: There were variations in
      perceived susceptibility to lung cancer between the CALD groups and between
      smokers and non-smokers. Fatalistic views towards lung cancer were apparent
      across all three CALD communities. There were low levels of awareness of lung
      cancer signs and symptoms, with the exception of haemoptysis. Differences in help
      seeking behaviour and levels of trust of general practitioners (GP) were
      apparent. CONCLUSION: Limited awareness of the signs and symptoms of lung cancer,
      combined with cultural perceptions about cancer, impacted on attitudes towards
      help-seeking behaviour in these three CALD communities. So what? The prevalence
      of smoking among Chinese men, Vietnamese men and Arabic-speaking communities in
      NSW puts them at increased risk of lung cancer. Health promotion initiatives for
      lung cancer should be tailored for CALD communities and could focus on increasing
      knowledge of key symptoms, awareness that ex-smokers are at risk and awareness of
      the diagnostic pathway including the importance of avoiding delays in help
      seeking.

PMID- 24739780
TI  - Nitbusters: lessons from a school-based intervention study to reduce head lice in
      a disadvantaged community.

PMID- 24739782
TI  - Occludin deficiency with BACE1 elevation in cerebral amyloid angiopathy.
AB  - OBJECTIVE: A significant cause of spontaneous hemorrhages in the elderly is
      cerebral amyloid angiopathy (CAA), which causes degeneration of cerebral vessels,
      but the mechanisms are unclear. METHODS: We isolated leptomeningeal vessels from
      rapidly autopsied brains (the average of postmortem intervals was 3.28 hours)
      from 9 patients with CAA and 10 age-matched controls, and used molecular, cell
      biology, and immunohistochemical approaches to examine beta-site APP-cleaving
      enzyme 1 (BACE1) protein expression and enzymatic activities as well as tight
      junction molecular components in small- and medium-sized arteries of the cerebral
      cortex and leptomeninges. RESULTS: We not only identified that the cerebral
      vessels, including leptomeningeal and cortical vessels, synthesize and express
      BACE1, but also found a significant elevation of both BACE1 protein levels and
      enzymatic activities in leptomeningeal vessels from patients with CAA. Moreover,
      overexpression of BACE1 in endothelial cells resulted in a significant reduction
      of occludin, a tight junction protein in blood vessels. CONCLUSION: These
      findings suggest that in addition to neurons, cerebral vascular cells express
      functional BACE1. Moreover, elevated vascular BACE1 may contribute to deficiency
      of occludin in cerebral vessels, which ultimately has a critical role in
      pathogenesis of CAA and its related hemorrhage.

PMID- 24739783
TI  - Structural MRI correlates of apathy symptoms in older persons without dementia:
      AGES-Reykjavik Study.
AB  - OBJECTIVE: We aimed to investigate the relation between apathy symptoms and
      structural brain changes on MRI, including white matter lesions (WMLs) and
      atrophy, in a large cohort of older persons. METHODS: Cross-sectional analyses
      are based on 4,354 persons without dementia (aged 76 +/- 5 years) participating
      in the population-based Age, Gene/Environment Susceptibility-Reykjavik Study.
      Apathy symptoms were assessed with 3 items from the 15-item Geriatric Depression
      Scale. Brain volumes and total WML volume were estimated on 1.5-tesla MRI using
      an automated segmentation program; regional WML load was calculated using a
      semiquantitative scale. Regression analyses were adjusted for age, sex,
      education, intracranial volume, vascular risk factors, physical activity, brain
      infarcts, depressive symptoms, antidepressants, and cognitive status. RESULTS:
      Compared to those with <2 apathy symptoms, participants with >= 2 apathy symptoms
      (49% of the cohort) had significantly smaller gray matter volumes (mean adjusted
      difference -3.6 mL, 95% confidence interval [CI] -6.2 to -1.0), particularly in
      the frontal and temporal lobes; smaller white matter volumes (mean adjusted
      difference -1.9 mL, 95% CI -3.6 to -0.3), mainly in the parietal lobe; and
      smaller thalamus volumes. They were also more likely to have WMLs in the frontal
      lobe (adjusted odds ratio = 1.08, 95% CI 0.9-1.3). Excluding participants with a
      depression diagnosis did not change the associations. CONCLUSIONS: In this older
      population without dementia, apathy symptoms are associated with a more diffuse
      loss of both gray and white matter volumes, independent of depression.

PMID- 24739784
TI  - Gap junctions: Inputs alter coupling strength.

PMID- 24739785
TI  - Nuclear and cytosolic JNK signalling in neurons.
AB  - It has been over 20 years since JUN amino-terminal kinases (JNKs) were identified
      as protein kinases that are strongly activated by cellular stress and that have a
      key role in apoptosis. Examination of Jnk-knockout mice and characterization of
      JNK behaviour in neuronal cells has further revealed the importance of the JNK
      family in the nervous system. As well as regulating neuronal death, JNKs govern
      brain morphogenesis and axodendritic architecture during development, and
      regulate important neuron-specific functions such as synaptic plasticity and
      memory formation. This Review examines the evidence that the spatial segregation
      of JNKs in neurons underlies their distinct functions and that compartment
      specific targeting of JNKs may offer promising new therapeutic avenues for the
      treatment of diseases of the nervous system, such as stroke and neurodegenerative
      disorders. 

PMID- 24739786
TI  - Restoring sensorimotor function through intracortical interfaces: progress and
      looming challenges.
AB  - The loss of a limb or paralysis resulting from spinal cord injury has devastating
      consequences on quality of life. One approach to restoring lost sensory and motor
      abilities in amputees and patients with tetraplegia is to supply them with
      implants that provide a direct interface with the CNS. Such brain-machine
      interfaces might enable a patient to exert voluntary control over a prosthetic or
      robotic limb or over the electrically induced contractions of paralysed muscles.
      A parallel interface could convey sensory information about the consequences of
      these movements back to the patient. Recent developments in the algorithms that
      decode motor intention from neuronal activity and in approaches to convey sensory
      feedback by electrically stimulating neurons, using biomimetic and adaptation
      based approaches, have shown the promise of invasive interfaces with sensorimotor
      cortices, although substantial challenges remain. 

PMID- 24739789
TI  - 3D nanostructure reconstruction based on the SEM imaging principle, and
      applications.
AB  - This paper addresses a novel 3D reconstruction method for nanostructures based on
      the scanning electron microscopy (SEM) imaging principle. In this method, the
      shape from shading (SFS) technique is employed, to analyze the gray-scale
      information of a single top-view SEM image which contains all the visible surface
      information, and finally to reconstruct the 3D surface morphology. It offers not
      only unobstructed observation from various angles but also the exact physical
      dimensions of nanostructures. A convenient and commercially available tool
      (NanoViewer) is developed based on this method for nanostructure analysis and
      characterization of properties. The reconstruction result coincides well with the
      SEM nanostructure image and is verified in different ways. With the extracted
      structure information, subsequent research of the nanostructure can be carried
      out, such as roughness analysis, optimizing properties by structure improvement
      and performance simulation with a reconstruction model. Efficient, practical and
      non-destructive, the method will become a powerful tool for nanostructure surface
      observation and characterization. 

PMID- 24739787
TI  - Astrocyte Ca2+ signalling: an unexpected complexity.
AB  - Astrocyte Ca(2+) signalling has been proposed to link neuronal information in
      different spatial-temporal dimensions to achieve a higher level of brain
      integration. However, some discrepancies in the results of recent studies
      challenge this view and highlight key insufficiencies in our current
      understanding. In parallel, new experimental approaches that enable the study of
      astrocyte physiology at higher spatial-temporal resolution in intact brain
      preparations are beginning to reveal an unexpected level of compartmentalization
      and sophistication in astrocytic Ca(2+) dynamics. This newly revealed complexity
      needs to be attentively considered in order to understand how astrocytes may
      contribute to brain information processing.

PMID- 24739788
TI  - How does the bilingual experience sculpt the brain?
AB  - The ability to speak two languages often marvels monolinguals, although
      bilinguals report no difficulties in achieving this feat. Here, we examine how
      learning and using two languages affect language acquisition and processing as
      well as various aspects of cognition. We do so by addressing three main
      questions. First, how do infants who are exposed to two languages acquire them
      without apparent difficulty? Second, how does language processing differ between
      monolingual and bilingual adults? Last, what are the collateral effects of
      bilingualism on the executive control system across the lifespan? Research in all
      three areas has not only provided some fascinating insights into bilingualism but
      also revealed new issues related to brain plasticity and language learning.

PMID- 24739790
TI  - Elastic stable intramedullary nailing versus Kirschner wire pinning: outcome of
      severely displaced proximal humeral fractures in juvenile patients.
AB  - BACKGROUND: Significantly displaced juvenile proximal humeral fractures (Neer
      Horowitz type 3 and 4) usually require reduction and fixation. The most commonly
      used fixation methods are Kirschner wire (K-wire) pinning or retrograde elastic
      stable intramedullary nailing (ESIN). However, results comparing the long-term
      outcome of both methods are absent in the literature. The aim of this study was
      to provide an outcome comparison of both techniques. METHODS: Included were 40
      patients treated between 1998 and 2008 and who had complete records concerning
      operation time, duration of hospital stay, and time until implant removal. The
      assessment of clinical (Disabilities of Arm, Shoulder and Hand [DASH] and
      Constant-Murley scores) and radiologic long-term outcome was possible in 31
      patients (78%). Preoperative, postoperative and follow-up radiographs of these
      patients were evaluated for angular deformity, reduction, and remodeling.
      RESULTS: The mean follow-up of the 31 patients (16 ESIN; 15 K-wire) was 5.8 +/-
      3.6 (standard deviation) years. The operative time of the primary fixation
      procedure was shorter in the ESIN group (P < .001), but the hospital stay and the
      time until implant removal were significantly longer. No significant difference
      was seen between the groups at follow-up for the mean DASH (ESIN, 1.44; K-wire,
      1.66) or Constant-Murley (ESIN, 89.5; K-wire, 92) scores. The neck-shaft angle
      was significantly improved by reduction in both groups (P < .001) and remained
      unchanged at follow-up. CONCLUSIONS: ESIN and K-wire pinning have a favorable and
      comparable functional outcome and therefore seem to be adequate methods for
      treating Neer-Horowitz type 3 and 4 proximal humeral fractures in juvenile
      patients. The initially achieved improvement of the neck-shaft angle can be
      maintained at long-term follow-up.

PMID- 24739791
TI  - Accuracy of patient-specific guided glenoid baseplate positioning for reverse
      shoulder arthroplasty.
AB  - BACKGROUND: The accuracy of reproducing a surgical plan during shoulder
      arthroplasty is improved by computer assistance. Intraoperative navigation,
      however, is challenged by increased surgical time and additional technically
      difficult steps. Patient-matched instrumentation has the potential to reproduce a
      similar degree of accuracy without the need for additional surgical steps. The
      purpose of this study was to examine the accuracy of patient-specific planning
      and a patient-specific drill guide for glenoid baseplate placement in reverse
      shoulder arthroplasty. METHODS: A patient-specific glenoid baseplate drill guide
      for reverse shoulder arthroplasty was produced for 14 cadaveric shoulders based
      on a plan developed by a virtual preoperative 3-dimensional planning system using
      thin-cut computed tomography images. Using this patient-specific guide, high
      volume shoulder surgeons exposed the glenoid through a deltopectoral approach and
      drilled the bicortical pathway defined by the guide. The trajectory of the drill
      path was compared with the virtual preoperative planned position using similar
      thin-cut computed tomography images to define accuracy. RESULTS: The drill
      pathway defined by the patient-matched guide was found to be highly accurate when
      compared with the preoperative surgical plan. The translational accuracy was 1.2
      +/- 0.7 mm. The accuracy of inferior tilt was 1.2 degrees  +/- 1.2 degrees . The
      accuracy of glenoid version was 2.6 degrees  +/- 1.7 degrees . CONCLUSION: The
      use of patient-specific glenoid baseplate guides is highly accurate in
      reproducing a virtual 3-dimensional preoperative plan. This technique delivers
      the accuracy observed using computerized navigation without any additional
      surgical steps or technical challenges.

PMID- 24739792
TI  - Reverse shoulder glenoid baseplate fixation: a comparison of flat-back versus
      curved-back designs and oval versus circular designs with 2 different offset
      glenospheres.
AB  - BACKGROUND: In this glenoid loosening study, we compared the fixation strength of
      multiple generic reverse shoulder glenoid baseplates that differed only in
      backside geometry and shape and size to optimize design from a fixation
      perspective. METHODS: The fixation strength of 4 generic baseplates was
      quantified in a low-density polyurethane substrate to isolate the contribution of
      baseplate profile and size (25 mm circular vs 25 * 34 mm oval) and backside
      geometry (flat back vs curved back) on fixation using 2 center-of-rotation
      glenospheres (0 mm and 10 mm lateral). The cyclic test simulated 55 degrees  of
      abduction as a 750 N load was continuously applied to induce a variable shear and
      compressive load. Before and after cyclic loading, baseplate displacement was
      measured in the directions of the applied static shear and compressive loads.
      Each generic baseplate was cyclically tested 7 times with each offset glenosphere
      for a total of 56 samples. RESULTS: Circular baseplates were associated with
      significantly more shear displacement in both the superior-inferior (SI) and
      anterior-posterior (AP) directions after cyclic loading than oval baseplates. No
      such significant differences in fixation were observed between flat-back and
      curved-back baseplates. Circular baseplates were also associated with
      significantly more SI and AP shear displacement with 10 mm glenospheres than with
      0 mm glenospheres. No significant difference in SI or AP motion was observed with
      oval baseplates between 0 mm and 10 mm glenospheres. DISCUSSION: Our results
      suggest that baseplate shape and size affects fixation strength more than
      backside geometry. The 25 * 34 mm oval baseplates showed better fixation
      characteristics than their 25 mm circular counterparts; no discernible difference
      in fixation was observed between flat-back and curved-back baseplates.

PMID- 24739793
TI  - The active and passive kinematic difference between primary reverse and total
      shoulder prostheses.
AB  - BACKGROUND: Reverse shoulder arthroplasty (RSA) and total shoulder arthroplasty
      (TSA) effectively decrease pain and improve clinical outcome. However,
      indications and biomechanical properties vary greatly. Our aim was to analyze
      both active and passive shoulder motion (thoracohumeral [TH], glenohumeral [GH],
      and scapulothoracic [ST]) and determine the kinematic differences between RSAs
      and TSAs. METHODS: During 3 range-of-motion (ROM) tasks (forward flexion,
      abduction, and axial rotation), the motion patterns of 16 RSA patients (19
      shoulders), with a mean age of 69 +/- 8 years (range, 58-84 years), and 17 TSA
      patients (20 shoulders), with a mean age of 72 +/- 10 years (range, 53-87 years),
      were measured. The mean length of follow-up was 22 +/- 10 months (range, 6-41
      months) for RSA patients and 33 +/- 18 months (range, 12-87 months) for TSA
      patients. Kinematic measurements were performed with a 3-dimensional
      electromagnetic tracking device. RESULTS: All patients showed better passive than
      active ROM. This difference was significantly larger for RSA patients than for
      TSA patients (TH in sagittal plane, 20 degrees  vs 8 degrees  [P = .001]; GH in
      sagittal plane, 16 degrees  vs 7 degrees  [P = .003]; TH in scapular plane, 15
      degrees  vs 2 degrees  [P < .001]; GH in scapular plane, 12 degrees  vs 0 degrees
      [P < .001]; and ST in scapular plane, 3 degrees  vs -2 degrees  [P = .032]).
      This finding also showed that in the scapular plane, TSA patients showed hardly
      any difference between active and passive ROM. Furthermore, TSA patients had 16
      degrees  to 17 degrees  larger active TH motion, 15 degrees  larger active GH
      motion, and 8 degrees  larger active ST motion compared with RSA patients. The GH
      ST ratios showed similar figures for both types of prostheses. CONCLUSION: TSA
      patients have larger active TH motion because in the scapular plane, they
      completely use the possible GH motion provided by the prosthetic design. This
      larger active ROM in TSA patients only applies for elevation and abduction, not
      for axial rotation or passive ROMs.

PMID- 24739794
TI  - Long-stemmed humeral components in primary shoulder arthroplasty.
AB  - BACKGROUND: Long-stemmed humeral components are often associated with revision
      shoulder arthroplasty. However, long-stemmed humeral components will likely prove
      useful in selected patients with extra large shoulders and in those with bone
      loss from nonarthroplasty causes and in humeral fractures. This study was
      developed to examine the frequency of use of longer humeral stems, identify the
      indications for their use, define the results, and enumerate the complications
      encountered. MATERIALS AND METHODS: Thirty-five primary shoulder arthroplasties
      were followed-up clinically and radiographically for at least 2 years or until
      revision surgery. The primary indications for use of an intermediate or long stem
      were a large humeral canal in 18 shoulders and severe preoperative metaphyseal or
      diaphyseal bone loss in 17. Average clinical follow-up was 6.5 years. RESULTS:
      Excellent or satisfactory results were achieved in 21 of 35 shoulders. No
      components met criteria to be considered radiographically at risk for clinical
      loosening. Intraoperative complications included an unrecognized nondisplaced
      diaphyseal fracture that later displaced in 1 shoulder. Late complications
      included deep infection in 1 and fracture nonunion in 1. CONCLUSIONS:
      Intermediate or long-stemmed humeral components proved useful in obtaining a
      secure distal fit in patients with a large humeral canal or in those with
      significant proximal bone loss. Worse clinical results were achieved in those
      with bone loss. Radiographic follow-up shows these components are at a low risk
      for loosening.

PMID- 24739795
TI  - Rotator cuff surgery in persons with spinal cord injury: relevance of a
      multidisciplinary approach.
AB  - BACKGROUND: This article is a prospective review of patients with spinal cord
      injury who underwent multidisciplinary consultation from January 2005 to
      September 2013 for pain in one or both shoulders. METHODS: We performed clinical,
      functional, and lesion evaluations of 38 patients with paraplegia and
      quadriplegia presenting with rotator cuff pathologies. RESULTS: Surgery was
      indicated and performed on 38 shoulders in 28 patients. The lesion assessment
      during surgery showed injuries that were more severe than one would have thought
      based on imaging data. The mean pain intensity rating in the operative and
      nonoperative groups was 0 and 1.6, respectively, at rest and 2 and 4.9,
      respectively, during paroxysmal peaks. On average, for patients who had surgery,
      the Functional Independence Measure score decreased by 2.3. The mean satisfaction
      index in operated patients was 8.5 of 10. CONCLUSIONS: When the surgical
      indication was based on a multidisciplinary decision, no negative results were
      reported that could have challenged the validity of this decision. Pain relief
      was the primary benefit reported after surgery. The functional status was
      modified because of the technical aids needed to prevent shoulder overuse. There
      are several arguments in favor of rotator cuff surgery for wheelchair-bound
      patients with spinal cord injury. Because of their functional impairments,
      wheelchair-bound patients will continue to overburden their shoulders after
      rotator cuff surgery. A multidisciplinary approach emerges as the solution to
      inform and educate patients to limit the risk of recurrence.

PMID- 24739796
TI  - Radiocapitellar prosthetic arthroplasty: a report of 6 cases and review of the
      literature.
AB  - BACKGROUND: Radiocapitellar prosthetic arthroplasty has recently been introduced
      to treat isolated degenerative arthritis of the radiocapitellar joint. Although
      this procedure is conceptually attractive and sound in situations in which radial
      head resection is inadequate, clinical experience is still limited. Its role in
      the treatment of isolated radiocapitellar degenerative arthritis in the
      ligamentous-intact elbow and forearm is not yet defined. Our purpose was to
      report the short-term results of 6 patients who were treated by radiocapitellar
      prosthetic arthroplasty for isolated radiocapitellar degenerative arthritis in
      the ligamentous-intact elbow, as well as to provide a review of the literature.
      METHODS: Six patients were treated by radiocapitellar prosthetic arthroplasty for
      isolated degenerative arthritis of the radiocapitellar joint in the ligamentous
      intact elbow. Their medical records were reviewed, and each patient was seen in
      the office. The mean follow-up period was 50 months (range, 30-64 months).
      RESULTS: The implant survival rate was 100%. Pain improved in all patients and
      all patients were satisfied. The mean flexion-extension arc increased from 98
      degrees  (range, 75 degrees -115 degrees ) to 110 degrees  (range, 105 degrees 
      120 degrees ) (P = .17), and the mean pronation-supination arc increased from 133
      degrees  (range, 75 degrees -115 degrees ) to 143 degrees  (range, 120 degrees 
      170 degrees ) (P = .34). The mean Disabilities of the Arm, Shoulder and Hand
      score was 24.3 (range, 6.7-52.5). According to the Mayo Elbow Performance Score,
      there were 3 excellent and 3 good results. CONCLUSION: The short-term follow-up
      results of radiocapitellar prosthetic arthroplasty for isolated radiocapitellar
      degenerative arthritis in the ligamentous-intact elbow and forearm seem
      favorable. LEVEL OF EVIDENCE: Level IV, case series, treatment study.

PMID- 24739797
TI  - The association between cubital tunnel morphology and ulnar neuropathy in
      patients with elbow osteoarthritis.
AB  - BACKGROUND: Morphologic changes in the cubital tunnel during elbow motion in
      patients with elbow osteoarthritis have not been examined in vivo. We examined
      changes in cubital tunnel morphology during elbow motion and characteristics of
      medial osteophyte development to elucidate whether cubital tunnel area and medial
      osteophyte size are factors contributing to cubital tunnel syndrome in patients
      with elbow osteoarthritis. METHODS: We performed computed tomography of 13
      primary osteoarthritic elbows in patients with cubital tunnel syndrome (group A)
      and 25 primary osteoarthritic elbows in patients without cubital tunnel syndrome
      (group B) at full extension, 90 degrees  of flexion, and full flexion. Cubital
      tunnel area, humeral and ulnar osteophyte area, and proportion of osteophytes
      within the cubital tunnel were analyzed at each position. RESULTS: Humeral
      osteophytes and osteophyte proportion within the cubital tunnel were larger at
      full flexion (24.7 mm(2) and 49.9% in group A; 18.7 mm(2) and 39% in group B) and
      90 degrees  of elbow flexion (20.3 mm(2) and 45.3% in group A; 10.2 mm(2) and
      30.2% in group B) than at full extension (9.0 mm(2) and 31.3% in group A; 2.3
      mm(2) and 12.5% in group B). These parameters were significantly greater in group
      A than in group B at full extension and 90 degrees  of flexion. CONCLUSIONS: The
      effect of medial osteophytes on the ulnar nerve, especially on the humeral side,
      rather than narrowing of the cubital tunnel, may be a causative factor for
      cubital tunnel syndrome with elbow osteoarthritis.

PMID- 24739798
TI  - Adipokines: another link between obesity and hypertension.

PMID- 24739799
TI  - Effect of eplerenone on insulin action in essential hypertension: a randomised,
      controlled, crossover study.
AB  - An association exists between hyperaldosteronism, hypertension and impaired
      insulin action. Eplerenone is a selective mineralocorticoid receptor antagonist;
      however, little is known about its effects on insulin action. The aim of this
      study was to determine the effect of eplerenone on insulin action in hypertensive
      adults, using the hyperinsulinaemic euglycaemic clamp. A randomised, controlled,
      double-blind, crossover design was employed. After a 6-week washout period,
      hypertensive, non-diabetic patients were treated with either eplerenone 25 mg
      twice daily or doxazosin 2 mg twice daily for 12 weeks. After each treatment
      period, insulin action was assessed by a hyperinsulinaemic euglycaemic clamp,
      with isotope dilution methodology. After washout, treatment groups were crossed
      over. Fifteen patients completed the study. There were no differences in fasting
      glucose, or fasting insulin between treatment with eplerenone or doxazosin. The
      measure of overall insulin sensitivity, exogenous glucose infusion rates during
      the last 30 min of the clamp, was similar with both treatments; 23.4 (3.9) MUmol
      kg(-1) min(-1) after eplerenone and 23.3 (3.6) MUmol kg(-1) min(-1) after
      doxazosin (P=0.83). Isotopically determined fasting endogenous glucose production
      rates were similar after both treatments (eplerenone 9.4 (0.6) MUmol kg(-1) min(
      1) vs doxazosin 10.6 (0.7) MUmol kg(-1) min(-1)). There was a trend for lower
      endogenous glucose production rates during hyperinsulinaemia following eplerenone
      compared with doxazosin (2.0 (0.8) MUmol kg(-1) min(-1) vs 4.1 (0.9) MUmol kg(-1)
      min(-1)). There was no difference in insulin stimulated peripheral glucose
      utilisation rates after treatment with eplerenone or doxazosin (25.4 (3.6) MUmol
      kg(-1) min(-1) vs 27.0 (3.9) MUmol kg(-1) min(-1)). This study gives reassuring
      evidence of the neutral effect of eplerenone on insulin action in hypertensive,
      non-diabetic patients.

PMID- 24739800
TI  - Low-dose spironolactone reduces plasma fibulin-1 levels in patients with type 2
      diabetes and resistant hypertension.
AB  - Diabetic patients with hypertension are at particularly high risk of vascular
      damage and consequently cardiovascular and renal disease. Fibulin-1, an
      extracellular matrix glycoprotein, is increased in arterial tissue and plasma
      from individuals with type 2 diabetes. This study aimed to evaluate whether
      antihypertensive treatment with spironolactone changes plasma fibulin-1 levels.
      In a multicenter, double-blind, randomized, placebo-controlled study, 119
      patients with type 2 diabetes and resistant hypertension were included. A dose of
      spironolactone 25 mg or matching placebo was added to previous treatment at
      randomization. Blood pressure (BP) and plasma fibulin-1 were measured at baseline
      and at 16 weeks follow-up. Overall, 112 patients completed the study. All
      measures of BP were reduced in the spironolactone group at follow-up. Plasma
      fibulin-1 was significantly reduced after spironolactone treatment (P=0.009), but
      increased after placebo (P=0.017). Baseline plasma fibulin-1 correlated with BP
      and estimated glomerular filtration rate. Increased levels of plasma fibulin-1
      (P=0.004) were observed in diabetic participants reporting erectile dysfunction
      as compared with participants who did not. Treatment with low-dose spironolactone
      reduced plasma fibulin-1 levels in patients with type 2 diabetes and resistant
      hypertension. This supports the hypothesis that the antihypertensive effect of
      the mineralocorticoid receptor blocker in part may be due to regression of
      vascular remodeling. 

PMID- 24739801
TI  - Can we identify response markers to antihypertensive drugs? First results from
      the IDEAL Trial.
AB  - Current antihypertensive strategies do not take into account that individual
      characteristics may influence the magnitude of blood pressure (BP) reduction.
      Guidelines promote trial-and-error approaches with many different drugs. We
      conducted the Identification of the Determinants of the Efficacy of Arterial
      blood pressure Lowering drugs (IDEAL) Trial to identify factors associated with
      BP responses to perindopril and indapamide. IDEAL was a cross-over, double-blind,
      placebo-controlled trial, involving four 4-week periods: indapamide, perindopril
      and two placebo. Eligible patients were untreated, hypertensive and aged 25-70
      years. The main outcome was systolic BP (SBP) response to drugs. The 112
      participants with good compliance had a mean age of 52. One in every three
      participants was a woman. In middle-aged women, the SBP reduction from drugs was 
      11.5 mm Hg (indapamide) and -8.3 mm Hg (perindopril). In men, the response was
      significantly smaller: -4.8 mm Hg (indapamide) and -4.3 (perindopril) (P for sex
      differences 0.001 and 0.015, respectively). SBP response to perindopril decreased
      by 2 mm Hg every 10 years of age in both sexes (P=0.01). The response to
      indapamide increased by 3 mm Hg every 10 years of age gradient in women (P=0.02).
      Age and sex were important determinants of BP response for antihypertensive drugs
      in the IDEAL population. This should be taken into account when choosing drugs a
      priori. 

PMID- 24739802
TI  - High normal blood pressure: to treat or not to treat?

PMID- 24739803
TI  - Food insecurity among Iraqi refugees living in Lebanon, 10 years after the
      invasion of Iraq: data from a household survey.
AB  - Iraqi refugees in Lebanon are vulnerable to food insecurity because of their
      limited rights and fragile livelihoods. The objective of the present study was to
      assess household food insecurity among Iraqi refugees living in Lebanon, almost
      10 years after the invasion of Iraq. A representative survey of 800 UN High
      Commissioner for Refugees-registered refugee households in Lebanon was conducted
      using multi-stage cluster random sampling. We measured food insecurity using a
      modified US Department of Agriculture household food security module. We
      collected data on household demographic, socio-economic, health, housing and
      dietary diversity status and analysed these factors by food security status. Hb
      level was measured in a subset of children below 5 years of age (n 85). Weighted
      data were used in univariate and multivariate analyses. Among the Iraqi refugee
      households surveyed (n 630), 20.1% (95% CI 17.3, 23.2) were found to be food
      secure, 35.5% (95% CI 32.0, 39.2) moderately food insecure and 44.4% (95% CI
      40.8, 48.1) severely food insecure. Severe food insecurity was associated with
      the respondent's good self-reported health (OR 0.3, 95% CI 0.2, 0.5), length of
      stay as a refugee (OR 1.1, 95% CI 1.0, 1.2), very poor housing quality (OR 3.3,
      95% CI 1.6, 6.5) and the number of children in the household (OR 1.2, 95% CI 1.0,
      1.4), and resulted in poor dietary diversity (P< 0.0001). Anaemia was found in
      41% (95% CI 30.6, 51.9) of children below 5 years of age, but was not associated
      with food insecurity. High food insecurity, low diet quality and high prevalence
      of anaemia in Iraqi refugees living in Lebanon call for urgent programmes to
      address the food and health situation of this population with restricted rights.

PMID- 24739804
TI  - Multi-method approach for characterizing the interaction between Fusarium
      verticillioides and Bacillus thuringiensis subsp. Kurstaki.
AB  - Bacterial antagonists used as biocontrol agents represent part of an integrated
      management program to reduce pesticides in the environment. Bacillus
      thuringiensis is considered a good alternative as a biocontrol agent for
      suppressing plant pathogens such as Fusarium. In this study, we used microscopy,
      flow cytometry, indirect immunofluorescence, and high performance liquid
      chromatography to determine the interaction between B. thuringiensis subsp.
      kurstaki LFB-FIOCRUZ (CCGB) 257 and F. verticillioides MRC 826, an important
      plant pathogen frequently associated with maize. B. thuringiensis showed a strong
      in vitro suppressive effect on F. verticillioides growth and inhibited fumonisin
      production. Flow cytometry analysis was found to be adequate for characterizing
      the fungal cell oscillations and death during these interactions. Further studies
      of the antagonistic effect of this isolate against other fungi and in vivo
      testing are necessary to determine the efficacy of B. thuringiensis subsp.
      kurstaki in controlling plant pathogens. This is the first report on the use of
      flow cytometry for quantifying living and apoptotic F. verticillioides cells and
      the B. thuringiensis Cry 1Ab toxin. 

PMID- 24739805
TI  - Preoperative symptoms and inguinal herniorrhaphy.

PMID- 24739806
TI  - Cyanobacterial biomass as carbohydrate and nutrient feedstock for bioethanol
      production by yeast fermentation.
AB  - BACKGROUND: Microbial bioconversion of photosynthetic biomass is a promising
      approach to the generation of biofuels and other bioproducts. However, rapid,
      high-yield, and simple processes are essential for successful applications. Here,
      biomass from the rapidly growing photosynthetic marine cyanobacterium
      Synechococcus sp. PCC 7002 was fermented using yeast into bioethanol. RESULTS:
      The cyanobacterium accumulated a total carbohydrate content of about 60% of cell
      dry weight when cultivated under nitrate limitation. The cyanobacterial cells
      were harvested by centrifugation and subjected to enzymatic hydrolysis using
      lysozyme and two alpha-glucanases. This enzymatic hydrolysate was fermented into
      ethanol by Saccharomyces cerevisiae without further treatment. All enzyme
      treatments and fermentations were carried out in the residual growth medium of
      the cyanobacteria with the only modification being that pH was adjusted to the
      optimal value. The highest ethanol yield and concentration obtained was 0.27 g
      ethanol per g cell dry weight and 30 g ethanol L(-1), respectively. About 90% of
      the glucose in the biomass was converted to ethanol. The cyanobacterial
      hydrolysate was rapidly fermented (up to 20 g ethanol L(-1) day(-1)) even in the
      absence of any other nutrient additions to the fermentation medium. CONCLUSIONS:
      Cyanobacterial biomass was hydrolyzed using a simple enzymatic treatment and
      fermented into ethanol more rapidly and to higher concentrations than previously
      reported for similar approaches using cyanobacteria or microalgae. Importantly,
      as well as fermentable carbohydrates, the cyanobacterial hydrolysate contained
      additional nutrients that promoted fermentation. This hydrolysate is therefore a
      promising substitute for the relatively expensive nutrient additives (such as
      yeast extract) commonly used for Saccharomyces fermentations.

PMID- 24739807
TI  - Cadmium toxicity induced alterations in the root proteome of green gram in
      contrasting response towards iron supplement.
AB  - Cadmium signifies a severe threat to crop productivity and green gram is a
      notably iron sensitive plant which shows considerable variation towards cadmium
      stress. A gel-based proteomics analysis was performed with the roots of green
      gram exposed to iron and cadmium combined treatments. The resulting data show
      that twenty three proteins were down-regulated in iron-deprived roots either in
      the absence (-Fe/-Cd) or presence (-Fe/+Cd) of cadmium. These down-regulated
      proteins were however well expressed in roots under iron sufficient conditions,
      even in the presence of cadmium (+Fe/+Cd). The functional classification of these
      proteins determined that 21% of the proteins are associated with nutrient
      metabolism. The other proteins in higher quantities are involved in either
      transcription or translation regulation, and the rest are involved in
      biosynthesis metabolism, antioxidant pathways, molecular chaperones and stress
      response. On the other hand, several protein spots were also absent in roots in
      response to iron deprivation either in absence (-Fe/-Cd) or presence (-Fe/+Cd) of
      cadmium but were well expressed in the presence of iron (+Fe/+Cd). Results
      suggest that green gram plants exposed to cadmium stress are able to change the
      nutrient metabolic balance in roots, but in the mean time regulate cadmium
      toxicity through iron supplements. 

PMID- 24739809
TI  - Expression of S100A6 in rat hippocampus after traumatic brain injury due to
      lateral head acceleration.
AB  - In a rat model of traumatic brain injury (TBI), we investigated changes in
      cognitive function and S100A6 expression in the hippocampus. TBI-associated
      changes in this protein have not previously been reported. Rat S100A6 was studied
      via immunohistochemical staining, Western blot, and reverse transcription
      polymerase chain reaction (RT-PCR) after either lateral head acceleration or
      sham. Reduced levels of S100A6 protein and mRNA were observed 1 h after TBI,
      followed by gradual increases over 6, 12, 24, and 72 h, and then a return to sham
      level at 14 day. Morris water maze (MWM) test was used to evaluate animal spatial
      cognition. TBI- and sham-rats showed an apparent learning curve, expressed as
      escape latency. Although TBI-rats displayed a relatively poorer cognitive ability
      than sham-rats, the disparity was not significant early post-injury. Marked
      cognitive deficits in TBI-rats were observed at 72 h post-injury compared with
      sham animals. TBI-rats showed decreased times in platform crossing in the daily
      MWM test; the performance at 72 h post-injury was the worst. In conclusion, a
      reduction in S100A6 may be one of the early events that lead to secondary
      cognitive decline after TBI, and its subsequent elevation is tightly linked with
      cognitive improvement. S100A6 may play important roles in neuronal degeneration
      and regeneration in TBI. 

PMID- 24739808
TI  - Importance of N-glycosylation on CD147 for its biological functions.
AB  - Glycosylation of glycoproteins is one of many molecular changes that accompany
      malignant transformation. Post-translational modifications of proteins are
      closely associated with the adhesion, invasion, and metastasis of tumor cells.
      CD147, a tumor-associated antigen that is highly expressed on the cell surface of
      various tumors, is a potential target for cancer diagnosis and therapy. A
      significant biochemical property of CD147 is its high level of glycosylation.
      Studies on the structure and function of CD147 glycosylation provide valuable
      clues to the development of targeted therapies for cancer. Here, we review
      current understanding of the glycosylation characteristics of CD147 and the
      glycosyltransferases involved in the biosynthesis of CD147 N-glycans. Finally, we
      discuss proteins regulating CD147 glycosylation and the biological functions of
      CD147 glycosylation. 

PMID- 24739810
TI  - ADMA/SDMA in elderly subjects with asymptomatic carotid atherosclerosis: values
      and site-specific association.
AB  - Asymmetric dimethylarginine (ADMA) is an endogenous nitric oxide synthase (NOS)
      inhibitor known as a mediator of endothelial dysfunction and atherosclerosis.
      Circulating ADMA levels are correlated with cardiovascular risk factors such as
      hypercholesterolemia, arterial hypertension, diabetes mellitus,
      hyperhomocysteinemia, age and smoking. We assessed the relationship between ADMA
      values and site-specific association of asymptomatic carotid atherosclerosis
      (intima-media thickness (CIMT) and plaque) in elderly subjects. One hundred and
      eighty subjects underwent a complete history and physical examination,
      determination of serum chemistries and ADMA levels, and carotid ultrasound
      investigation (CUI). All subjects had no acute or chronic symptoms of carotid
      atherosclerosis. Statistical analyses showed that high plasma levels of ADMA/SDMA
      were positively correlated to carotid atherosclerosis (CIMT and plaque)
      (p<0.001), with significant site-specific association. Total cholesterol, low
      density lipoprotein cholesterol, triglycerides and C-reactive protein plasma
      concentrations were significantly associated with asymptomatic carotid
      atherosclerosis (p<0.001). High serum concentrations of ADMA and SDMA were
      associated with carotid atherosclerotic lesions as measured by CIMT ad plaque and
      may represent a new marker of asymptomatic carotid atherosclerosis in elderly
      subjects.

PMID- 24739811
TI  - Quality control and stability studies with the monoclonal antibody, trastuzumab:
      application of 1D- vs. 2D-gel electrophoresis.
AB  - Recombinant monoclonal antibodies (rmAbs) are medicinal products obtained by rDNA
      technology. Consequently, like other biopharmaceuticals, they require the
      extensive and rigorous characterization of the quality attributes, such as
      identity, structural integrity, purity and stability. The aim of this work was to
      study the suitability of gel electrophoresis for the assessment of charge
      heterogeneity, post-translational modifications and the stability of the
      therapeutic, recombinant monoclonal antibody, trastuzumab. One-dimensional, SDS
      PAGE, under reducing and non-reducing conditions, and two-dimensional gel
      electrophoresis were used for the determination of molecular mass (Mr), the
      isoelectric point (pI), charge-related isoform patterns and the stability of
      trastuzumab, subjected to stressed degradation and long-term conditions. For the
      assessment of the influence of glycosylation in the charge heterogeneity pattern
      of trastuzumab, an enzymatic deglycosylation study has been performed using N
      glycosidase F and sialidase, whereas carboxypeptidase B was used for the lysine
      truncation study. Experimental data documented that 1D and 2D gel electrophoresis
      represent fast and easy methods to evaluate the quality of biological medicinal
      products. Important stability parameters, such as the protein aggregation, can be
      assessed, as well. 

PMID- 24739812
TI  - Comparative study of electroless copper film on different self-assembled
      monolayers modified ABS substrate.
AB  - Copper films were grown on (3-Mercaptopropyl)trimethoxysilane (MPTMS), (3
      Aminopropyl)triethoxysilane (APTES) and 6-(3-(triethoxysilyl)propylamino)-1,3,5-
      triazine-2,4-dithiol monosodium (TES) self-assembled monolayers (SAMs) modified
      acrylonitrile-butadiene-styrene (ABS) substrate via electroless copper plating.
      The copper films were examined using scanning electron microscopy (SEM) and X-ray
      diffraction (XRD). Their individual deposition rate and contact angle were also
      investigated to compare the properties of SAMs and electroless copper films. The
      results indicated that the formation of copper nuclei on the TES-SAMs modified
      ABS substrate was faster than those on the MPTMS-SAMs and APTES-SAMs modified ABS
      substrate. SEM images revealed that the copper film on TES-SAM modified ABS
      substrate was smooth and uniform, and the density of copper nuclei was much
      higher. Compared with that of TES-SAMs modified resin, the coverage of copper
      nuclei on MPTMS and APTES modified ABS substrate was very limited and the copper
      particle size was too big. The adhesion property test demonstrated that all the
      SAMs enhanced the interfacial interaction between copper plating and ABS
      substrate. XRD analysis showed that the copper film deposited on SAM-modified ABS
      substrate had a structure with Cu(111) preferred orientation, and the copper film
      deposited on TES-SAMs modified ABS substrate is better than that deposited on
      MPTMS-SAMs or APTES-SAMs modified ABS resins in electromigrtion resistance. 

PMID- 24739813
TI  - An integrated epigenetic and transcriptomic analysis reveals distinct tissue
      specific patterns of DNA methylation associated with atopic dermatitis.
AB  - Epigenetic alterations are increasingly recognized as mechanisms for disease
      associated changes in genome function and important risk factors for complex
      diseases. The epigenome differs between cell types and so far has been
      characterized in few human tissues only. In order to identify disease-associated
      DNA methylation differences for atopic dermatitis (AD), we investigated DNA from
      whole blood, T cells, B cells, as well as lesional and non-lesional epidermis
      from AD patients and healthy controls. To elicit functional links, we examined
      epidermal mRNA expression profiles. No genome-wide significant DNA methylation
      differences between AD cases and controls were observed in whole blood, T cells,
      and B cells, and, in general, intra-individual differences in DNA methylation
      were larger than interindividual differences. However, striking methylation
      differences were observed between lesional epidermis from patients and healthy
      control epidermis for various CpG sites, which partly correlated with altered
      transcript levels of genes predominantly relevant for epidermal differentiation
      and innate immune response. Significant DNA methylation differences were
      discordant in skin and blood samples, suggesting that blood is not an ideal
      surrogate for skin tissue. Our pilot study provides preliminary evidence for
      functionally relevant DNA methylation differences associated with AD,
      particularly in the epidermis, and represents a starting point for future
      investigations of epigenetic mechanisms in AD. 

PMID- 24739814
TI  - School closures during the 2009 influenza pandemic: national and local
      experiences.
AB  - BACKGROUND: School closure is a non-pharmaceutical intervention that was
      considered in many national pandemic plans developed prior to the start of the
      influenza A(H1N1)pdm09 pandemic, and received considerable attention during the
      event. Here, we retrospectively review and compare national and local experiences
      with school closures in several countries during the A(H1N1)pdm09 pandemic. Our
      intention is not to make a systematic review of country experiences; rather, it
      is to present the diversity of school closure experiences and provide examples
      from national and local perspectives. METHODS: Data were gathered during and
      following a meeting, organized by the European Centres for Disease Control, on
      school closures held in October 2010 in Stockholm, Sweden. A standard data
      collection form was developed and sent to all participants. The twelve
      participating countries and administrative regions (Bulgaria, China, France, Hong
      Kong Special Administrative Region (SAR), Italy, Japan, New Zealand, Serbia,
      South Africa, Thailand, United Kingdom, and United States) provided data.
      RESULTS: Our review highlights the very diverse national and local experiences on
      school closures during the A(H1N1)pdm09 pandemic. The processes including who was
      in charge of making recommendations and who was in charge of making the decision
      to close, the school-based control strategies, the extent of school closures, the
      public health tradition of responses and expectations on school closure varied
      greatly between countries. Our review also discusses the many challenges
      associated with the implementation of this intervention and makes recommendations
      for further practical work in this area. CONCLUSIONS: The single most important
      factor to explain differences observed between countries may have been the
      different public health practises and public expectations concerning school
      closures and influenza in the selected countries.

PMID- 24739815
TI  - Electroacupuncture at ST36 accelerates the recovery of gastrointestinal motility
      after colorectal surgery: a randomised controlled trial.
AB  - OBJECTIVES: To evaluate whether electroacupuncture (EA) at ST36 can accelerate
      the recovery of gastrointestinal motility after colorectal surgery. METHODS:
      Forty patients of American Society of Anesthesiologists physical status II and
      III undergoing elective open resection of malignant colorectal tumours were
      included in this study. Using a sealed envelope method, the patients were
      randomly divided into two groups either receiving EA (EA group) or sham EA (SEA
      group). Data regarding the recovery of bowel function (times to the first bowel
      sounds, passage of flatus and defaecation) were collected and analysed. RESULTS:
      In the EA group, the time intervals from surgery to the first bowel movement and
      passage of flatus were shorter than in the SEA group (13+/-10 h vs 19+/-13 h,
      p<0.05 and 23+/-14 h vs 32+/-18 h, p<0.05, respectively). There was no
      significant difference between the groups regarding the time to first defaecation
      (68+/-45 h vs 72+/-53 h, p>0.05). CONCLUSIONS: EA at ST36 accelerates the
      recovery of gastrointestinal motility after colorectal surgery. TRIAL
      REGISTRATION: JJ22011-15.

PMID- 24739816
TI  - Review of methyl methacrylate (MMA)/tributylborane (TBB)-initiated resin adhesive
      to dentin.
AB  - This review, focusing mainly on research related to methyl
      methacrylate/tributylborane (MMA/TBB) resin, presents the early history of dentin
      bonding and MMA/TBB adhesive resin, followed by characteristics of resin bonding
      to dentin. Bond strengths of MMA/TBB adhesive resin to different adherends were
      discussed and compared with other bonding systems. Factors affecting bond
      strength (such as conditioners, primers, and medicaments used for dental
      treatment), bonding mechanism, and polymerization characteristics of MMA/TBB
      resin were also discussed. This review further reveals the unique adhesion
      features between MMA/TBB resin and dentin: in addition to monomer diffusion into
      the demineralized dentin surface, graft polymerization of MMA onto dentin
      collagen and interfacial initiation of polymerization at the resin-dentin
      interface provide the key bonding mechanisms. 

PMID- 24739817
TI  - Fracture resistance of endodontically treated premolars restored with lithium
      disilicate CAD/CAM crowns or onlays and luted with two luting agents.
AB  - The purpose of the present study is to evaluate the fracture resistance of
      endodontically treated maxillary premolars restored using CAD/CAM onlays or
      crowns and luted with two types of resin cement. Forty all-ceramic crowns and
      twenty onlays were fabricated on maxillary premolars using the Cerec 3 system
      (n=10). The abutments were randomly subjected to two different procedures:
      Endodontic treatment was performed on forty teeth restored through a mesio
      occlusal-distal (MOD) cavity preparation with composite resin fillings; twenty
      teeth without endodontic treatment served as control. In endodontically treated
      teeth restored using IPS e.max CAD crowns or onlays, the fracture loads were
      lower than those of the control. Endodontic treatment of teeth restored using
      CAD/CAM crowns does not impair the fracture load but shows more severe fractures
      than teeth restored using CAD/CAM onlays. This suggests that a CAD/CAM onlay
      might be an effective method for the restoration of endodontically treated
      premolars with MOD cavity defect. 

PMID- 24739818
TI  - Electron beam lithography with feedback using in situ self-developed resist.
AB  - Due to the lack of feedback, conventional electron beam lithography (EBL) is a
      'blind' open-loop process where the exposed pattern is examined only after ex
      situ resist development, which is too late for any improvement. Here, we report
      that self-developing nitrocellulose resist, for which the pattern shows up right
      after exposure without ex situ development, can be used as in situ feedback on
      the e-beam distortion and enlargement. We first exposed identical test pattern in
      nitrocellulose at different locations within the writing field; then, we examined
      in situ at high magnification the exposed patterns and adjusted the beam (notably
      working distance) accordingly. The process was repeated until we achieved a
      relatively uniform shape/size distribution of the exposed pattern across the
      entire writing field. Once the beam was optimized using nitrocellulose resist,
      under the same optimal condition, we exposed the common resist PMMA. We achieved
      approximately 80-nm resolution across the entire writing field of 1 mm * 1 mm, as
      compared to 210 nm without the beam optimization process. 

PMID- 24739819
TI  - Automated single-cell motility analysis on a chip using lensfree microscopy.
AB  - Quantitative cell motility studies are necessary for understanding biophysical
      processes, developing models for cell locomotion and for drug discovery. Such
      studies are typically performed by controlling environmental conditions around a
      lens-based microscope, requiring costly instruments while still remaining limited
      in field-of-view. Here we present a compact cell monitoring platform utilizing a
      wide-field (24 mm(2)) lensless holographic microscope that enables automated
      single-cell tracking of large populations that is compatible with a standard
      laboratory incubator. We used this platform to track NIH 3T3 cells on
      polyacrylamide gels over 20 hrs. We report that, over an order of magnitude of
      stiffness values, collagen IV surfaces lead to enhanced motility compared to
      fibronectin, in agreement with biological uses of these structural proteins. The
      increased throughput associated with lensfree on-chip imaging enables higher
      statistical significance in observed cell behavior and may facilitate rapid
      screening of drugs and genes that affect cell motility.

PMID- 24739820
TI  - Acquired nephrogenic diabetes insipidus in a dog with leptospirosis.
AB  - A 5 year old male neutered Cairn Terrier was evaluated for signs of polyuria and
      polydipsia. Initial hematology and chemistry panels were unremarkable and
      urinalysis showed a persistent hyposthenuria. Eleven days later, the dog became
      lethargic, inappetent and had developed acute renal failure. The dog was
      ultimately euthanized due to a poor response to treatment. Microscopic
      agglutination titres were consistent with a diagnosis of leptospirosis. The
      initial hyposthenuria in this case was consistent with acquired nephrogenic
      diabetes insipidus. This is an uncommon presentation of leptospirosis that has
      not previously been described to progress to acute renal failure. Leptospirosis
      should be considered as a differential diagnosis in any dog presenting with
      polyuria and polydipsia and these patients should be treated as a zoonotic risk. 

PMID- 24739822
TI  - Retraction notice.

PMID- 24739823
TI  - Histomorphological features of pancreas and liver in chronic alcoholics--an
      analytical study in 390 autopsy cases.
AB  - INTRODUCTION: Chronic pancreatitis and liver disease are two conditions that
      commonly co-exist in chronic alcoholics with variable incidences. AIM: To
      evaluate frequency pancreatitis in patients with a history of chronic alcohol
      abuse. MATERIALS AND METHODS: A total of 390 autopsies over 11 year's period were
      included in the study. Gross and microscopic assessment of liver and pancreas
      were performed. Available clinical and laboratory parameters were recorded.
      RESULTS: Age ranged from 22 to 65 years with a mean age of 45.32 years. All 390
      consecutive patients included in the study were males. Majority of the patients
      had primarily presented with alcohol related liver diseases whereas few had
      presented with features of pancreatitis. Micronodular cirrhosis was present in
      292 cases. Features of chronic pancreatitis were observed in 42 cases and 8 of
      these cases had associated changes of acute hemorrhagic pancreatitis. Prevalence
      of pancreatitis was more in cirrhotics as compared to non-cirrhotics, and acute
      pancreatitis was mostly seen in non-cirrhotics. Dominant pattern of fibrosis was
      perilobular followed by periductal, intralobular and diffuse. CONCLUSION: Chronic
      pancreatitis as evidence by the presence of parenchymal fibrosis was more
      frequently observed in alcoholic cirrhosis cases than that in non-cirrhotic
      alcoholic liver disease, thereby suggesting common underlying pathobiology in the
      development of fibrosis in liver as well as in pancreas.

PMID- 24739825
TI  - CagA+ H. pylori filtrate induces cytokine IL-8 secretion by esophageal squamous
      carcinoma EC 109 cells via a p38 pathway.
AB  - BACKGROUND: The relationship between Helicobacter pylori (Hp) infection and the
      risk of esophageal squamous cell carcinoma is unclear. AIM: The purpose was to
      investigate the effects of CagA+ Hp on esophageal squamous carcinoma Ec 109 cells
      in vitro and explore the molecular mechanisms underlying these effects. MATERIALS
      AND METHODS: Ec 109 cells were treated with CagA+ Hp filtrate at a concentration
      of 1.0 mg/mL or 50 MUg/mL in vitro, proliferation and apoptosis of Ec 109 cells
      were assayed, the secretion of IL-8 was measured by ELISA, and the levels of Src
      homology-2 domain-containing phosphatase (SHP-2) mRNAs was assayed by RT-PCR..
      Furthermore, after pretreatment of Ec109 cells with the specific p38 mitogen
      activated protein kinase (MAPK) inhibitor SB203580, the p38 pathway was detected.
      RESULTS: CagA+ Hp filtrate enhanced both the proliferation and apoptosis of Ec
      109 cells. In addition, cytokine IL-8 release was significantly increased, and
      the expression of SHP-2 mRNA declined sharply in the CagA+ Hp group. Furthermore,
      after pretreatment of Ec109 cells with the specific p38 MAPK inhibitor SB203580,
      Ec109 cells proliferation and IL-8 secretion were inhibited. CONCLUSIONS: Our
      results suggest that CagA+ Hp filtrates could induce proliferation and the
      secretion of IL-8 by Ec109 cells in vitro. IL-8 secretion was induced through the
      activation of the p38 MAPK signal pathway.

PMID- 24739824
TI  - Mutation profiling in gallbladder cancer in Indian population.
AB  - AIM: Gallbladder cancer is an aggressive malignancy usually diagnosed at late
      stage. The molecular genetics of this cancer is heterogeneous and not well
      established. Mutation profiling of gallbladder cancer was performed through
      massarray technology with an aim to identify molecular markers involved in the
      tumor pathogenesis that can be helpful as markers for early diagnosis and targets
      for therapy. MATERIALS AND METHODS: Forty nine cases of gallbladder cancer were
      screened through Sequenom Massarray technology for 390 mutations across 30 genes
      in formalin fixed paraffin embedded archived tissues and the results of mutation
      profiling was correlated with tumor characteristics. Mutations were observed in 9
      of 49 cases across four genes--TP53 (four cases), CTNNB1 (two cases), PIK3CA (two
      cases), and KRAS (one case). Six of these cases were well differentiated but of
      eight of them belonged to stage II to IV disease. Six cases had associated
      gallstones. CONCLUSION: The mutation frequency found in gallbladder cancer is
      comparable to the data available in literature. Identification of PIK3CA and KRAS
      mutations would help in formulating more efficacious targeted approach for
      management. Studies with large number of cases would help in exploring more
      targets and better classification of these cancers at genetic level.

PMID- 24739826
TI  - Paraganglioma of the urinary bladder: a clinicopathologic spectrum of a series of
      14 cases emphasizing diagnostic dilemmas.
AB  - BACKGROUND: Paraganglioma (PG) of the urinary bladder is a rare neuroendocrine
      neoplasm, accounting for < 0.1% of all bladder tumours. Distinction from
      urothelial carcinoma is imperative as management and prognosis vary markedly. In
      this report, we describe our experience with the histopathology of paragangliomas
      of the urinary bladder with emphasis on the histologic features that have led to
      their being misdiagnosed as conventional urothelial cancer and, most importantly,
      those that will help pathologists recognize this rare tumor of the bladder.
      MATERIALS AND METHODS: All cases of PG of urinary bladder diagnosed at our
      institute from 2002-2012 were retrieved and diagnosis confirmed in accordance
      with WHO classification. Clinical and treatment details were obtained from
      hospital medical records. RESULTS: Fourteen cases of PG of urinary bladder
      including 5 consult cases were analysed. These included 11 transurethral
      resections +/- partial cystectomies, 2 partial cystectomies and 1 radical
      cystectomy. Two out of the 5 consult cases had been submitted with a diagnosis of
      urothelial carcinoma and 1 with that of a rhabdomyosarcoma. Age ranged from 15-84
      years (median, 43 years) with a male to female ratio of 1:2.5. Presenting
      symptoms were haematuria, dysuria and flank pain; only 1 case had antecedent
      hypertension. Histologically, typical 'zellballen' (72%), diffuse (21%) and
      ribbon-like (7%) growth patterns amidst a richly vascularised stroma were seen.
      Muscularis propria invasion and necrosis was present in 72% and 21%,
      respectively. Substantial cautery artifacts led to misdiagnosis in the 3
      erroneous cases. Tumour cells were positive for chromogranin, synaptophysin;
      sustentacular cells were S-100 positive. Follow up was available in 6 patients;
      median follow-up was 29 months (8-120 months). One patient developed distant
      metastasis in cervical lymph node 10 years after diagnosis; remaining were alive
      without evidence of disease. CONCLUSIONS: Paraganglioma of the urinary bladder is
      a rare tumor and may be misdiagnosed as urothelial cancer especially on TURBT,
      but a high index of suspicion, careful search for the characteristic histological
      features and supportive immunohistochemical studies should lead to a correct
      diagnosis.

PMID- 24739827
TI  - The correlation between p16 expression and INK4a locus mutation with grades and
      stages in oral squamous cell carcinoma.
AB  - OBJECTIVE: p16INK4a is a tumor suppressor gene playing a critical role.
      Researches have indicated the gene to be altered in oral squamous cell carcinoma.
      Present studies have tried to assess the correlation between p16INK4a expression
      and INK4a locus mutation in relation to grades and stages of this tumor.
      MATERIALS AND METHODS: Expression of p16INK4a was studied immunohistochemically
      in 58 oral squamous sell carcinoma samples and INK4a locus mutation was
      determined by polymerase chain reaction (PCR) and conformation sensitive gel
      electrophoresis (CSGE). RESULTS: Expression of p16INK4a was higher in stage1
      compared to stage 2, 3, and 4 (P = 0.234). The difference was not significant in
      grade 1, 2, and 3 (P = 0.671). The average values of total score (TS) were
      significantly higher in stage1 compared to stage 2, 3, and 4 (P = 0.035). The
      average values of complete score (CS) were higher in stage 1 compared to stage 2,
      3, and 4 (P = 0.061). The research did not show a significant correlation between
      lymph node involvement and p16INK4a expression (P = 0.491). It seems that 5.1%
      (3/58) of samples have mutation in INK4a locus. CONCLUSION: Loss of p16INK4a
      expression occurred in initial stages of oral squamous cell carcinoma. Evaluation
      of TS and CS for p16INK4a might be a useful clinical indicator concerning the
      tumor. However, gene mutation is believed to have minor rate of genetic
      alteration in carcinogenesis.

PMID- 24739828
TI  - Heparin: induced thrombocytopenia: incidence and laboratory approach to diagnosis
      in Indians.
AB  - BACKGROUND AND OBJECTIVES: One of the most common complications of heparin
      administration is heparin-induced thrombocytopenia (HIT) which can also lead to
      catastrophic thrombotic events. The problem of identifying the cause of
      thrombocytopenia, as due to heparin, in patients with multiple co-morbid
      conditions is very essential for management. Thus, the laboratory investigations
      for diagnosis of HIT play a pivotal role. The objective of the study was to
      arrive at the incidence of HIT in ethnic Indian population and provide a decision
      after analysis of tests used to diagnose HIT. MATERIALS AND METHODS: 125
      consecutive patients (Power of study being 80%) undergoing open heart surgery and
      receiving unfractionated heparin were taken as subjects. Blood samples were
      collected a day before the surgery and days 1, 3, 5 and 7 after surgery. The
      cases were categorized into probable and unlikely groups depending on the
      clinical presentation and degree fall of platelet count. Anti-heparin PF4
      associated antibodies were detected using rapid-ID gel microtyping system and
      ELISA tests. HIT was also tested using functional assays: heparin-induced
      platelet aggregation test (PAT) and the rapid luminographic assay of heparin
      induced ATP release. RESULTS: Of the 125 patients, 11 patients were clinically
      labeled as probable HIT and 29 patients were clinically labeled as unlikely HIT.
      There were seven confirmed cases of HIT cases that were positive for one
      functional and one immunological assay. Only one case of HITT was encountered.
      Accordingly, the incidence of HIT was found to be 5.6% and that of HITT to be
      0.8%. ELISA tests were positive in 21 cases (17%) which demonstrated the presence
      of anti-HPF4 antibodies in non-HIT cases as well. It was found that the rapid gel
      test had sensitivity comparable to functional assay with better specificity than
      ELISA. INTERPRETATION AND CONCLUSIONS: Incidence of HIT in ethnic Indian
      population is 5.6%. Patients with a drop of >50% in platelet count should be
      perused as a likely candidate of HIT. These cases should be subjected to the ID
      HPF4 antibody assay as this is a rapid test, can be done for individual cases,
      and has better specificity and similar sensitivity than ELSIA. Cases with
      clinically probable HIT and a positive ID-HPF4 assay can be taken as confirmed
      cases of HIT. However, cases clinically unlikely for HIT and a positive ID-HPF4
      assay should be subjected to another test to establish the diagnosis of HIT.

PMID- 24739829
TI  - What regulates hepcidin in poly-transfused beta-Thalassemia Major: erythroid
      drive or store drive?
AB  - BACKGROUND: Hepcidin, a key regulator of iron homeostasis, is increased by iron
      overload and inflammation while suppressed by hypoxia. In spite of iron overload
      in beta-Thalassemia Major (beta-TM), a paradoxical decrease in hepcidin is
      observed. AIM: To assess the opposing effects of enhanced erythropoiesis due to
      anemia and iron overloading on hepcidin in beta-TM patients. SETTING AND DESIGN:
      This prospective observational study was done at our tertiary care hospital.
      MATERIALS AND METHODS: Eighty-three pediatric polytransfused (> 20 transfusions)
      patients of beta-TM were compared with 70 children who served as controls. Serum
      assays for ferritin, transferrin receptors (sTfR) and hepcidin were performed.
      STATISTICAL ANALYSIS: Independent Student t test was used to compare variables
      between both the groups. A Pearson correlation coefficient was used to find any
      correlation between ferritin, sTfR and hepcidin. RESULTS: The mean value of
      hepcidin in beta-TM children was 13.88+/-10.68 ng/ml (range, 0.9-60 ng/ml) and
      showed significant negative correlation with sTfR (r = -0.296, P < 0.0066).
      However, there was no correlation of hepcidin with ferritin. Ferritin and sTfR
      were significantly elevated in beta-TM children compared to controls (P < 0.001).
      The mean serum hepcidin/ferritin index in the study group (0.00552) was
      significantly lower (P value < 0.001) than the controls (0.378) thus indicating
      inappropriate levels of hepcidin to iron overload. CONCLUSION: In polytransfused
      beta-TM children increased iron demand dominates over iron overload in regulating
      hepcidin. In spite of excessive iron load, the inappropriate hepcidin levels may
      further contribute to iron overload enhancing iron toxicity.

PMID- 24739830
TI  - Establishing a normal reference range for thromboelastography in North Indian
      healthy volunteers.
AB  - BACKGROUND: Thromboelastography (TEG) is relatively recent assay to analyze the
      coagulation state of a blood sample, providing a continuous visualization of
      physical changes occurring during blood coagulation. There is a paucity of
      published literature on assessment of coagulation status using TEG in Indian
      population. AIM: The primary aim of the following study is to establish normal
      reference values for TEG in North Indian healthy volunteers and secondary aim is
      to compare them with conventional plasma-based routine coagulation tests and the
      manufacturers reference range. MATERIALS AND METHODS: A total of 200 healthy
      volunteers comprised of 100 males and 100 females of age groups between 20 and 50
      years, were enrolled over a period of 1 year, i.e., 2011-2012. Thromboelastometry
      (TEM) was performed on TEM-A automated thromboelastometer (Framar Biomedica,
      Rome, Italy), using whole blood non-additive (360 ul). TEG parameters analyzed
      were r-time, k-time, alpha-angle, maximal amplitude (MA). Prothrombin time (PT),
      activated partial thromboplastin time (aPTT) and platelet count was performed for
      all volunteers. The 95% reference range was calculated as (mean-1.96 standard
      deviation [SD]) to (mean + 1.96 SD). RESULTS: Our reference values for 95% of 200
      volunteers were r-time: 1.8-14.2 min, k-time: 0.7-7.3 min, alpha-angle: 27.3-72.3
      degrees  and MA: 32.1-87.9 mm. Maximum clot strength was higher in women compared
      with men, however statistically insignificant. Overall 14.5% (29/200) of the
      volunteers had at least one abnormal parameter while 74% (149/200) had deranged
      TEG values using the manufacturer's reference range. Statistically significant
      variation was seen in r-time for 84.8% (P < 0.001), for k-time, in 87.1% (P <
      0.001), for alpha-angle in 83.7% (P < 0.001) and for MA in 84% (P < 0.001),
      between the manufacturer and our reference range. CONCLUSION: The efficacy of
      classical coagulation test has been well-established; on the contrary TEG is a
      fairly recent assay and its utility for patient management remains to be
      demonstrated. We observed TEG to be oversensitive in determining coagulopathy
      where there is no clinical presentation. The manufacturer's reference values may
      not be appropriate for different ethnicity. TEG may give an overall
      representation of hemostasis; however, it cannot replace the conventional
      coagulation tests. We recommend the determination of normal TEG values by each
      laboratory for their target population.

PMID- 24739831
TI  - C-reactive protein in patients with Guillain Barre syndrome.
AB  - CONTEXT: C-reactive protein (CRP) is an acute phase reactant, widely used as a
      biomarker for various infectious and inflammatory conditions. Guillain-Barriota
      syndrome (GBS) is an acute, autoimmune, polyradiculoneuropathy, triggered by
      infectious agents such as Campylobacter jejuni. GBS is generally precipitated 1-3
      weeks following C. jejuni infection which suggests a humoral immunopathogenic
      mechanism. AIMS: Basal CRP levels were estimated in sera of patients with GBS and
      compared with adequate controls. SETTINGS & DESIGN: The study population was
      divided into 4 groups: (i) GBS group included 45 newly diagnosed GBS patients;
      (ii) Neurological control (NC) group comprised of 59 patients with non-paralytic
      neurological symptoms/disorders; (iii) Non-neurological controls (NNC) comprised
      of 43 patients having no neurological symptoms and (iv) Healthy controls (HC)
      comprised of 101 healthy subjects. MATERIALS AND METHODS: CRP was evaluated using
      slide latex agglutination test (LAT) and enzyme linked immunosorbent assay
      (ELISA). STATISTICAL ANALYSIS: Statistical analysis was done by the Chi-square
      test. RESULTS: CRP by LAT was positive in 24.4% GBS group, 34% NC group and 44%
      NNC group. The range of titer in CRP positive samples in the three patient groups
      (GBS, NC, NNC) was at concentration of 0.6 mg/dl to 19.2 mg/dl. Similar results
      were also obtained by ELISA in the patient groups. None of the HC subjects was
      positive for detectable levels of CRP. High basal level of CRP was detected in
      patients with GBS. CONCLUSION: Autoimmune conditions like GBS can stimulate the
      production of a high level of inflammation resulting in an increase in the CRP
      production.

PMID- 24739832
TI  - Prevalence of Chlamydia trachomatis in women attending sexually transmitted
      disease clinics in the Colombo district, Sri Lanka.
AB  - BACKGROUND: In Sri Lanka little is known about the prevalence of Chlamydia
      trachomatis (CT) infection. Objective was to determine the prevalence of CT in
      female patients attending sexually transmitted disease (STD) clinics in the
      Colombo district. MATERIALS AND METHODS: A descriptive cross-sectional study was
      carried out for the prevalence of CT in all female patients (n = 168) more than
      18 years of age, attending two STD clinics in the Colombo district from January
      to May 2012. Endocervical swabs were collected and tested for CT using the
      Amplicor CT/NG polymerase chain reaction assay. RESULTS: Prevalence of CT in
      females attending the STD clinics in the Colombo district was 8.3%. Mean age of
      those infected with CT was 32.9 years (SD +/- 8.2). Majority of females with CT
      infections were Sinhalese and married. There was no significant association with
      age, ethnicity or being married or not. Females who did not attend school, or had
      their education only up to Grade 5 were significantly found to have six times the
      risk of having CT infection (95% CI = 1.8-22.6). A significant association was
      found with number of sexual partners but not with commercial sex work or past
      history of STD. CONCLUSIONS: Prevalence of CT was moderately high in this
      population.

PMID- 24739833
TI  - Study of virulence factors of uropathogenic Escherichia coli and its antibiotic
      susceptibility pattern.
AB  - CONTEXT: Urinary tract infection (UTI) is one of the most common nosocomial
      infections, caused by Escherichia coli. This study determined the presence of
      virulence factors in the organism and correlates it with the multi-drug
      resistance (MDR). AIMS: The aim of the following study is to assess the virulence
      factors of uropathogenic E. coli and antibiotic susceptibility pattern. SETTINGS
      AND DESIGN: This was a prospective study conducted in the Department of
      Microbiology in PT. B. D. Sharma, PGIMS, Rohtak. SUBJECTS AND METHODS: The study
      was conducted over a period of 1 year. Urine samples received were processed as
      per standard microbiological procedures. Virulence factors such as hemolysin,
      hemagglutination, cell surface hydrophobicity, serum resistance, gelatinase and
      siderophore production were studied. The antimicrobial susceptibility was done as
      per Clinical and Laboratory Standard Institute Guidelines. STATISTICAL ANALYSIS
      USED: The data was analyzed by using SPSS(Statistical Package for the social
      sciences) IBM Corporation version 17.0. A two sided P <= 0.05 was considered to
      be significant. RESULTS: Hemolysin production was seen in 47.4%, hemagglutination
      in 74.8%, cell surface hydrophobicity in 61%, serum resistance in 59%, gelatinase
      in 67.5% and siderophore production in 88% isolates. Nitrofurantoin was found to
      be most effective followed by, gatifloxacin and gentamicin. Twenty nine percent
      (29.62%) isolates were MDR. CONCLUSIONS: Therefore, the knowledge of virulence
      factors of E. coli and their antibiotic susceptibility pattern will help in
      better understanding of the organism and in the treatment of UTI.

PMID- 24739834
TI  - Multidrug resistant NDM-1 metallo-beta-lactamase producing Klebsiella pneumoniae
      sepsis outbreak in a neonatal intensive care unit in a tertiary care center at
      central India.
AB  - OBJECTIVE: The objective of the following study is to detect genes encoding
      carbapenem resistance in Klebsiella pneumoniae sepsis outbreak in a neonatal
      intensive care unit (NICU). MATERIALS AND METHODS: Antibiotic sensitivity test
      was performed by standard Kirby Bauer disc diffusion technique and minimum
      inhibitory concentrations of antibiotics was determined by VITEK-2. Polymerase
      chain reaction (PCR) assays and sequencing was used to determine the presence of
      beta-lactamase encoding genes. Conjugation experiments were performed to
      determine the transferability of beta-lactamase. Isolate relatedness were
      determined by repetitive-element PCR (REP), enterobacterial repetitive intergenic
      consensus (ERIC) PCR and random amplified polymorphic deoxyribonucleic acid
      (RAPD). RESULTS: All the isolates were completely resistant to the second and
      third generation cephalosporins tested as well as carbapenems. Susceptibility
      profiling of the isolates indicated that 100% retained susceptibility to
      tigecycline and colistin. Conjugation experiments indicated that blaNDM-1 was
      transferable and likely through a plasmid-mediated event. All the isolates showed
      the presence of blaNDM-1 with co association of blaCTX-M-15. REP-PCR, ERIC-PCR
      and RAPD revealed a single clonal type circulating in NICU environment.
      CONCLUSION: Co-production of NDM-1 with CTX-M-15 in K. pneumoniae isolates was
      detected for the first time in our NICU. Transmission of plasmid carrying these
      resistant genes to other members of Enterobacteriaceae will increase the
      incidence of multidrug resistance. Early detection of these genes will help in
      prevention and adequate infection control by limiting the spread of these
      organisms.

PMID- 24739835
TI  - Tuberculous neuritis: a rare sequel of a common disease.
AB  - Tuberculosis (TB), a disease caused by Mycobacterium tuberculosis is an
      infectious disease that continues to be a significant health problem in a
      developing country like India. The cause of peripheral neuropathy associated with
      tuberculosis is controversial. Possibilities include the toxic effects of anti
      tuberculous chemotherapy (especially, rifampicin, streptomycin & ethambutol),
      immune mediated neuropathy, direct invasion of nerves, vasculitic neuropathy,
      compressive neuropathy, and meningitic reaction. This report describes an unusual
      finding of tuberculous granulomas in the peripheral nerve (Greater auricular
      nerve) of a patient ,who presented with a painful neck swelling. Granulomas were
      present in Greater auricular nerve (C2,C3) biopsy specimen associated with
      tuberculous peri-neuritis, but with no more specific indications of the mechanism
      of the neuropathy. 

PMID- 24739836
TI  - Post chemotherapy blood and bone marrow regenerative changes in childhood acute
      lymphoblastic leukemia a prospective study.
AB  - CONTEXT: This study was done to assess the Serial peripheral blood and bone
      marrow changes in patients of Acute Lymphoblastic Leukemia on chemotherapy. AIMS:
      To assess the therapy related serial bone marrow changes in patients of Acute
      Lymphoblastic Leukemia. SETTINGS AND DESIGN: Prospective study, carried out in
      Lymphoma- Leukemia Lab, Department of Pathology, K.G.M.U from March 2011 to March
      2012. A total of 60 cases were studied. MATERIALS AND METHODS: History, complete
      hemogram, bone marrow examination at pretherapy (Day-0), intratherapy (Day-14),
      and end of induction chemotherapy (Day-28) were done. Peripheral blood smears
      were evaluated at regular interval to assess clearance of blast cells.
      STATISTICAL ANALYSIS USED: The statistical analysis was done using SPSS
      (Statistical Package for Social Sciences) Version 15.0 statistical Analysis
      Software. The values were represented in Number (%) and Mean +/- SD. The
      following Statistical formulas were used: Mean, standard deviation, Chi square
      test, Paired "t" test, Student 't' test, Level of significance P. RESULTS:
      Incidence of ALL-L1 (46.7%) and ALL-L2 (53.3%) was equal. ALL-L2 patients had
      poor survival.Day 0 (D-0) bone marrow was hypercellular with flooding of marrow
      by leukemic cells. High levels of tumor load at D'0' were associated with poor
      survival. 14 th day of Induction phase showed significant decrease in hemoglobin
      and TLC as compared to D '0' parameters. D28 showed marrow regeneration.
      Cellularity, Blast%, and Leukemic Index showed significant drop from day '0' to
      day 14 due to myelosupression, whereas regeneration reflected by increased
      cellularity as per day 28 marrow. Lymphocytosis (>20%) at end of induction
      chemotherapy had better survival and longer remission.Risk of mortality was
      directly proportional to blast clearance and was a major independent prognostic
      factor for achievement of complete remission. CONCLUSIONS: A bone marrow
      examination at the end of induction chemotherapy provides information whether
      patient has achieved remission with regeneration of cells or still has residual
      leukemia. If the patient is in remission, maintenance treatment is started and if
      not more intensive chemotherapy or bone marrow transplantation may be embarked
      upon.

PMID- 24739837
TI  - Your dilemma, my identity: unusual immunogenetic profiles of pediatric B cell
      acute lymphoblastic leukemia.
AB  - B-cell acute lymphoblastic leukemia (B-ALL) is characterized by CD19 expression,
      which is one of the most important prerequisites, along with expression of CD10,
      CD22 and/or CD79a. Rearrangements involving MLL gene are seen in CD10- B-ALL (pro
      B cell origin) and t(9;11)(p21;q23) is most commonly reported in acute myeloid
      leukemia (AML), where it is known to carry very good prognosis in pediatric AMLs
      and rarely in acute lymphoblastic leukemia (ALL). We report a case of CD10+, CD19
      pediatric ALL with rearrangements of MLL gene as a result of t(9;11)(p21;q23),
      thus conferring a very poor prognosis. The case emphasizes use of comprehensive
      panel of antibodies for flow cytometric immunophenotyping and cytogenetic
      correlation for correct diagnosis and prognostication.

PMID- 24739838
TI  - Early dengue diagnosis by nonstructural protein 1 antigen detection: rapid
      immunochromotography versus two the enzyme-linked immunosorbent assay kits.
AB  - Dengue is known for its serious life-threatening complications. New rapid kits
      available recently in India target circulating non-structural protein (NS1)
      antigen from day one onwards. The sensitivity and specificity of a newly
      introduced rapid combo kit against two conventional ELISA kits is assessed. The
      performance of this kit is quite satisfactory since excellent agreement of 94.26%
      was observed with particular reference to NS1 antigen detection among all three
      kits namely Rapid SD Bioline dengue Duo (SD Korea), InBios DENV Detect NS1 ELISA,
      USA and dengue Early ELISA, Panbio, Australia. The false positivity of the rapid
      kit is very low since its specificity as for as NS1 antigen detection is
      concerned is 98.33%. The use of combination kit helps to detect additional cases
      of dengue, which are negative for NS1 antigen but positive for IgM and/or IgG
      antibodies, thus facilitating early diagnosis in remote areas and small
      laboratorie. 

PMID- 24739839
TI  - Myoepithelial carcinoma of palate: case report.
AB  - Myoepithelial carcinoma is an uncommon malignant salivary gland neoplasm with a
      predilection for parotid gland. However, its occurrence in minor salivary glands
      is considerably less with only 28 cases being reported in the literature. We
      report a case of myoepithelial carcinoma of palate in a 50-year-old woman.
      Computed tomography and magnetic resonance imaging revealed an extensive lesion
      in the palate. Microscopically, the tumor exhibited a wide spectrum of
      cytomorphologic features that overlap with other salivary gland tumors.
      Immunohistochemistry served as an adjunct in the diagnosis of the lesion.
      Clinical, radiographic, and histopathologic correlation along with
      immunohistochemical profile enabled to arrive at a diagnosis of myoepithelial
      carcinoma. 

PMID- 24739840
TI  - Case of pulmonary pneumocytoma: a probable cytological diagnosis with
      histopathological confirmation.
AB  - Pneumocytoma is a rare benign tumor of the lung that usually presents as a
      solitary pulmonary nodule. It is believed to arise from the primitive
      undifferentiated respiratory epithelium. We report a case of pulmonary
      pneumocytoma that was suspected on needle aspiration smears and confirmed
      histologically. This case describes the cytological features of pneumocytoma that
      are rarely described in textbooks. 

PMID- 24739841
TI  - Multifocal pulmonary mucinous cystic neoplasm with ovarian type stroma, a new
      finding in an extremely rare case report.
AB  - Primary pulmonary mucinous cystic neoplasm is a rare tumor and there are only a
      few case reports in the English literature. Herein we report a very unusual
      multifocal pulmonary mucinous neoplasm. Microscopic sections revealed ovarian
      type stroma which was diffusely positive for estrogen receptor, same as its
      pancreaticobiliary counterpart. To the best of our knowledge such a presentation
      of pulmonary mucinous neoplasm has not been previously reported in the English
      literature. 

PMID- 24739842
TI  - Androgen-secreting steroid cell tumor of the ovary.
AB  - Steroid cell tumors (SCTs), not otherwise specified of the ovary are rare
      subgroup of sex cord tumors, which account for less than 0.1% of all ovarian
      tumors and also that will present at any age. The majority of these tumors
      produce steroids with testosterone being the most common. A case of a 28-year-old
      woman who presented with symptoms of virilization is reported. Although SCTs are
      generally benign, there is a risk for malignant transformation. Surgery is the
      most important and hallmark treatment. 

PMID- 24739843
TI  - Triple composite tumor of stomach: a rare combination of alpha fetoprotein
      positive hepatoid adenocarcinoma, tubular adenocarcinoma and large cell
      neuroendocrine carcinoma.
AB  - A 50-year-old male patient presented with pain abdomen of 6 months duration.
      Computed tomography scan revealed a large mass in the stomach occluding the
      lumen. Histopathology revealed a triple composite tumor comprising of tubular
      adenocarcinoma arising on a background of high-grade dysplasia, hepatoid
      adenocarcinoma (positive for Hep Par-1 and alpha fetoprotein) and large cell
      neuroendocrine carcinoma (positive for synaptophysin and chromogranin) with nodal
      metastasis.Triple composite tumors are distinctly rare with few reports in
      literature. 

PMID- 24739844
TI  - Pleomorphic xanthoastrocytoma with anaplastic features: a case report.
AB  - Pleomorphic xanthoastrocytoma has been considered as an astrocytic tumor with
      relatively favorable prognosis. It corresponds to WHO Grade-II neoplasm.
      Recently, several patterns with relatively poor prognosis have been recorded and
      a new concept of "PXA with anaplastic features" has been proposed. The present
      case is about a 9-year-old girl who presented with symptoms of recurrent
      headache, seizures and poor academic performance. MRI revealed left fronto
      parietal irregular enhancing mass lesion with callosal involvement and right mid
      brain arteriovenous malformation. Clinical and radiological examination was
      suggestive of a high grade glial neoplasm/PNET. A diagnosis of high grade glial
      neoplasm was rendered on the squash smears submitted for frozen sections based on
      the presence of spindle cells, admixed with pleomorphic bizarre, giant cells with
      multilobated nuclei showing few atypical mitosis and abundant eosinophilic
      cytoplasm. Frontal craniotomy with debulking of the tumor was performed and
      permanent sections revealed a biphasic glial neoplasm with spindle cells arranged
      in fascicles admixed with bizarre multinucleated giant cells showing abundant
      vacuolated and lipidized cytoplasm, nuclear hyperchromasia with intranuclear
      inclusions. Eosinophilic granular bodies, mitosis of 7/10 HPF, micro vascular
      proliferation, necrosis and invasion into the underlying brain parenchyma were
      noted. With these histomorphological findings a diagnosis of pleomorphic
      xanthoastrocytoma with anaplastic features was rendered. 

PMID- 24739845
TI  - Clear cell papillary cholangiocarcinoma: a case report with review of literature.
AB  - Clear cell papillary cholangiocarcinoma is a rare variant of intrahepatic
      cholangiocarcinoma with only nine reported cases in the literature. This tumor
      needs to be differentiated from clear cell variant of hepatocellular carcinoma
      and other metastatic clear cell carcinomas. This tumor is known to have better
      prognosis compared to conventional intrahepatic cholangiocarcinoma. Hence, it is
      important to correctly diagnose this entity and differentiate it from other
      histologic mimics. We describe clinical, histopathological, and
      immunohistochemical findings of one such rare case in a 66-year-old gentleman who
      was incidentally detected to have an intrahepatic tumor at routine ultrasound
      examination.A review of all the similar cases reported so far in the literature
      is also provided. 

PMID- 24739846
TI  - Cytokeratin-positive rib osteosarcoma metastasizing to the small intestine.
AB  - Osteosarcoma (OS) is a malignant tumor in which osteoid or bone is produced
      directly by tumor cells. Some OS cells are positive for cytokeratin (CK) and
      epithelial membrane antigen by immunohistochemistry (IHC) and this may lead to a
      misdiagnosis of metastatic carcinoma, particularly when the tumor location is
      unusual. On the other hand, gastrointestinal metastasis of OS is rare. We present
      the case of a 67-year-old Japanese man with a small intestinal intussusception
      due to metastasis of a CK-positive rib OS. The tumor cells were positive for CK,
      osteopontin and osteonectin by IHC and a diagnosis of a CK-positive chest wall OS
      metastasizing to the small intestine was considered. Osteoid or bone formation
      was histologically absent and therefore chest wall OS had to be differentially
      diagnosed from metastatic carcinoma of unknown origin. A postmortem histological
      analysis confirmed a rib OS. Awareness of CK-positive OS is important for making
      a correct diagnosis and for disease management and an immunohistochemical
      analysis of the tumor for expression of osteopontin and osteonectin may be used
      to support the diagnosis. In addition, this case shows that rib OS can
      metastasize to the gastrointestinal tract, albeit rarely, which may induce an
      intestinal intussusception. 

PMID- 24739847
TI  - Pelvic mature cystic teratoma with neuroendocrine carcinoma: report of a rare
      association and review of literature.
AB  - Extra-gonadal malignant transformation of teratoma is rare and there are only a
      few reports available citing malignancy arising in the non-germ cell components.
      We hereby report a case of a 35-year-old female, who presented with lower
      backache with a radiologically identifiable mass lesion in the pre-sacral region.
      Clinical and radiological findings suggested the possibility of a cystic
      teratoma. Histopathological examination and relevant immunohistochemical tests
      detected a mature cystic teratoma with features of a grade 2 neuroendocrine tumor
      in it. Like the index case, most of the previously reported cases of teratoma
      with malignant transformation of the somatic components were found in extra
      gonadal site. This case is being reported to emphasize that any extra-gonadal
      mass in reproductive age group, even if it appears radiologically and per
      operatively benign, must be subjected to histopathological examination to rule
      out possibility of malignant transformation of the germ cell or non-germ cell
      components. 

PMID- 24739848
TI  - Hepatoid adenocarcinoma of stomach: case report of a rare histological variant.
AB  - Hepatoid adenocarcinoma of the stomach is a rare form of gastric carcinoma with
      specific clinicopathological features and extremely poor prognosis. Here, we
      report a case of a 60-year-old male patient who presented in the outpatient
      department with pain abdomen and constitutional symptoms. Radiological
      examination revealed a growth involving the antrum of the stomach while the liver
      and spleen were normal. The serum alpha fetoproteins were 6590 ng/ml. The patient
      underwent a partial gastrectomy and microscopic examination of the growth showed
      two types of histological patterns. Majority of the tumor displayed hepatoid
      differentiation with adenocarcinomatous foci. Periodic acid Schiff positive
      intracytoplasmic hyaline globules were seen. The tumor was immunohistochemically
      positive for alpha fetoprotein. The patient underwent radical gastrectomy,
      received chemotherapy and has been on follow-up for the past 12 months. Though
      known to be an aggressive neoplasm early diagnosis of hepatoid adenocarcinoma can
      help improve the prognosis of the disease. 

PMID- 24739849
TI  - Incidentally discovered goblet cell carcinoid clinically presenting as acute
      intestinal obstruction: a case report with review of literature.
AB  - Goblet cell carcinoid (GCC) is a rare variant of carcinoid tumor that exclusively
      involves the appendix. It usually occurs in 5th-6th decade with the most common
      clinical presentation being acute appendicitis. The natural history of this tumor
      is intermediate between carcinoids and adenocarcinomas. We here report a case of
      GCC diagnosed incidentally in a patient presenting with acute intestinal
      obstruction. Ultrasonographic examination supported the clinical diagnosis of
      acute intestinal obstruction, following which the patient underwent laparotomy
      and resection of ileum along with appendix was done. On gross pathological
      examination, a nodular growth was present on the tip and body of appendix that
      was yellow in color with a semi-solid to mucoid consistency on cut section. On
      microscopy, lakes of mucin with few acinar structures floating in them were seen.
      The submucosa as well as serosa were infiltrated by clusters of goblet cells and
      well-formed acini, with little atypia. Glands and nests were positive for
      periodic acid Schiff and immunohistochemistry showed focal chromogranin
      positivity in glandular structures, thereby confirming the diagnosis of GCC.
      Although the prognosis of GCC is better than adenocarcinomas, it is one of the
      carcinoids having a poorer outcome when compared with other variants of carcinoid
      tumor. Therefore, it is important to rule out other differential diagnoses of
      goblet cell carcinoid, the most important being mucinous adenocarcinomas.

PMID- 24739850
TI  - Krukenberg tumor in a young woman: a rare presentation.
AB  - Krukenberg tumors mostly occur after 40 years. Metastatic ovarian tumors in young
      age are very rare and reported to be 2% of all the cases. Thirty percent of all
      ovarian neoplasms occurring during childhood and adolescence are malignant. A 25
      year-old woman, parity-2, presented with abdominal distension, pain in abdomen
      and amenorrhea. On examination, 18 weeks lump was palpable, firm to hard in
      consistency, non-tender and mobile. On ultrasonography bilateral ovarian tumors
      were reported, without any peritoneal free fluid. Total abdominal hysterectomy
      with bilateral salpingo-oophorectomy was performed. Microscopic examination
      revealed signet ring cells with glandular differentiation, diffusely invading the
      ovarian parenchyma. Tumor cells exhibited strong, diffuse immunopositivity for
      CEA with focal strong immunopositivity for CK7 and CK20 and immunonegativity for
      SATB2. Diagnosis of Krukenberg tumor was made. Endoscopic biopsy confirmed the
      diagnosis of adenocarcinoma stomach. This case is reported because of its rarity
      in younger age group.

PMID- 24739851
TI  - Cutaneous amyloidosis and insulin with coexistence of acanthosis nigricans.
AB  - Skin is one of the important organs affected by amyloidosis which is
      characterized by extracellular deposition of fibrillary proteins having
      homogenous, eosinophilic on routine staining with distinct tinctorial properties.
      Nodular cutaneous amyloidosis is rare and may affect dermis, subcutis and also
      vascular walls. Nodular amyloid deposits in the deeper dermis occurring at the
      site of insulin injection are a rare observation, which is described here. This
      description indicates that cutaneous amyloidosis may be associated with local
      subcutaneous injections of insulin and may clinically mimic a neoplasm or
      lipodystrophic lesion. 

PMID- 24739852
TI  - Malignant peripheral nerve sheath tumor of adrenal gland with heterologus osseous
      differentiation in a case of Von Recklinghausen's disease.
AB  - Malignant peripheral nerve sheath tumor (MPNST) of the adrenal gland is extremely
      rare. Most of them occur in association with neurofibromatosis, ganglioneuroma or
      as part of a composite tumor such as pheochromocytoma. Only seven cases of MPNST
      of the adrenal gland have been reported in the literature till date.
      Discriminating this entity from other soft tissue sarcomas and gastrointestinal
      stromal tumor of the adrenal gland has important diagnostic and therapeutic
      implications. Moreover, the tumor size and pattern of expression for certain
      immunohistochemical markers may serve as independent predictors of
      aggressiveness. Herein we present a 24-years-old male with features of Von
      Recklinghausen's disease who presented with large left adrenal gland malignant
      peripheral nerve sheath tumor. 

PMID- 24739853
TI  - Testicular swelling: a rare manifestation of chronic lymphocytic leukemia
      presenting with Richter's syndrome.
AB  - Richter syndrome (RS) represents the clinico-pathologic transformation of
      indolent lymphomas to an aggressive lymphoma, most commonly diffuse large B-cell
      lymphoma. Majority of the patients have a previous diagnosis of Chronic
      Lymphocytic Leukemia and the median time to transformation is 2-4 years. De novo
      RS is extremely uncommon. RS frequently arises in the lymph nodes or bone marrow
      and rarely presents with extra nodal involvement, common sites being the
      gastrointestinal tract, eye, central nervous system, lung and kidney. Involvement
      of testis by RS is extremely rare and we came across only one such reported case
      in the literature. We are reporting this case as our patient presented with de
      novo RS at an extremely uncommon extra nodal site, testis. 

PMID- 24739854
TI  - Suprasellar salivary gland-like pleomorphic adenoma.
AB  - Suprasellar salivary gland-Like pleomorphic adenoma is not a common disease and
      seldom reported so far. We are reporting a case of a 23-year-old man with
      recurrent suprasellar salivary gland-like pleomorphic adenoma, who underwent an
      operation of subtotal, subfrontal resection under the wrong pathology diagnosis
      of benign teratoma in another hospital 4-year-ago. Four years later, he was
      admitted to our hospital for additional visual loss of the right eye (left, 1.0;
      right, 0.4) resulting from tumor regrowth. Magnetic resonance imaging revealed
      that suprasellar extension and compressed optic chiasm resulted in visual
      disturbance of the patient. The tumor was totally excised and histological
      examination evidenced the pathological features of intrasellar salivary gland
      like pleomorphic adenoma. The patient did not receive any further treatment and
      he is free from tumor recurrence for 30 months after the operation. From this
      point of view, clinical prognosis of intrasellar salivary gland-like pleomorphic
      adenoma was good after total surgical resection. 

PMID- 24739855
TI  - Fatal Klebsiella pneumoniae meningitis in a patient with diabetes mellitus and
      Hansen's disease.
AB  - Klebsiella is a Gram-negative bacterium that causes different types of health
      care-associated infections including pneumonia, bloodstream infections, surgical
      site infections and meningitis. We report here a case of Klebsiella pneumoniae
      meningitis in a patient with diabetes mellitus and Hansen's disease. A middle
      aged man with a known case of diabetes mellitus and Hansen's disease presented
      with the complaints of blurred vision in the left eye and the patient was found
      to have cataract. Patient was operated for cataract and Intraocular lens
      implanted. Patient developed headache and vomiting on the 4th post-operative day.
      Lumbar puncture was carried out and gram stain of cerebrospinal fluid showed Gram
      negative bacilli in the direct smear and culture yielded a heavy growth of K.
      pneumoniae. The patient was treated with antimicrobials according to the
      susceptibility pattern. He initially showed improvement but later on developed
      altered sensorium and hypotension. Patient succumbed to infection in spite of all
      medical attention.

PMID- 24739856
TI  - Blood stream infection by an emerging pathogen Oligella ureolytica in a cancer
      patient: case report and review of literature.
AB  - Oligella ureolytica is an emerging bacteria rarely implicated as a human
      pathogen. It is infrequently recovered from clinical specimens probably because
      of inadequate processing of non-fermenting oxidase positive Gram negative
      bacilli. We present here a case of a 30 year old male suffering from right lung
      adenocarcinoma (moderately differentiated) with multiple abdominal lymph node
      metastasis with Syringohydromyelia whose blood culture yielded Oligella
      ureolytica in pure culture. Oligella ureolytica isolation in pure culture and the
      patient's response to targeted treatment supported that Oligella ureolytica was
      the true causative agent of the blood stream infection. Early suspicion,
      diagnosis and treatment with potent antibiotics are needed to prevent further
      complications resulting from infection with this emerging pathogen. 

PMID- 24739857
TI  - Intraductal papillary neoplasm of the bile duct: a rarity.

PMID- 24739858
TI  - Metaplastic breast carcinoma with extensive chondrosarcomatous differentiation.

PMID- 24739859
TI  - Expansile congenital soft-tissue mass: a massive presentation.

PMID- 24739860
TI  - Isolated adrenal metastasis: a case report.

PMID- 24739861
TI  - Papillary variant of medullary carcinoma thyroid.

PMID- 24739862
TI  - Methotrexate-induced pneumonitis and myocarditis.

PMID- 24739863
TI  - Primary small cell carcinoma of the renal pelvis with adenocarcinoma component.

PMID- 24739864
TI  - Calcifying fibrous pseudotumor of the mediastinum: a rare case report.

PMID- 24739865
TI  - Anaplastic lymphoma kinase (ALK) positive diffuse large B cell lymphoma in a 20
      year old: a rare entity.

PMID- 24739866
TI  - Sensitivity testing of Staphylococcus aureus.

PMID- 24739867
TI  - Biofilm production in Gram-positive isolates causing urinary tract infection in a
      tertiary care hospital.

PMID- 24739868
TI  - Pneumocephalus in mixed aerobic and anaerobic (Bacteroides fragilis) meningitis.

PMID- 24739869
TI  - Chronic lymphocytic leukemia developing in a case of chronic myelogenous
      leukemia: some observations.

PMID- 24739871
TI  - Cell-penetrating peptoids: introduction of novel cationic side chains.
AB  - During the last decade peptoid-based molecular transporters have been broadly
      applied. They are highly valued for their easy synthesis and their superior
      stability against enzymatic degradation. The special structure of peptoids
      generally allows introducing a variety of different side chains. Yet, the
      cationic side chains of cell-penetrating peptoids displayed solely lysine- or
      arginine-like structures. Thus this report is intended to extend the spectrum of
      cationic peptoid side chains. Herein, we present novel functional groups, like
      polyamines, aza-crown ethers, or triphenylphosphonium ions that are introduced
      into peptoids for the first time. In addition, the obtained peptoids were tested
      for their cell-penetrating properties. 

PMID- 24739872
TI  - A study of human papillomavirus on vaginally inserted sex toys, before and after
      cleaning, among women who have sex with women and men.
AB  - OBJECTIVES: The objective of the study was to determine the potential of human
      papillomavirus (HPV) transmission via shared sex toys, and determine whether
      cleaning practices implemented by the study participants were effective. METHODS:
      Vibrator 1 was composed of thermoplastic elastomer. Vibrator 2 was composed of
      silicone. Twelve women, recruited from a university, used each vibrator on
      separate occasions and provided self-collected vaginal and vibrator samples
      (obtained from the vibrator shaft and handle), collected immediately after use,
      immediately after cleaning with a commercially available cleaner, and 24 h after
      cleaning. Vaginal and vibrator samples were assessed for HPV DNA by the Roche
      Linear Array HPV Genotyping Test. RESULTS: HPV was detected in the vaginal
      samples of 9/12 (75%) women. Vibrator 1 shaft swabs were HPV positive before
      cleaning in 89% (8/9), immediately after cleaning in 56% (5/9), and 24 h after
      cleaning in 40% (2/5) of those that were HPV positive immediately after cleaning.
      Vibrator 2 shaft swabs were HPV positive before cleaning in 67% (6/9),
      immediately after cleaning in 44% (4/9), and 24 h after cleaning in none.
      CONCLUSIONS: HPV was detected on at least one vibrator immediately after use in
      the women with vaginal HPV. This supports the potential for HPV transmission via
      shared sex toy use, and is additionally supported by continued detection of HPV
      up to 24 h after standard cleaning. The data add to understanding of the range of
      sexual behaviours associated with HPV transmission, and the need for evidence
      based recommendations for sex toy cleaning.

PMID- 24739873
TI  - Disease load at conception predicts survival in later epidemics in a historical
      French-Canadian cohort, suggesting functional trans-generational effects in
      humans.
AB  - OBJECTIVE: Functional trans-generational and parental effects are potentially
      important determinants of health in several mammals. For humans, the existing
      evidence is weak. We investigate whether disease exposure triggers functional
      trans-generational response effects among humans by analyzing siblings who were
      conceived under different disease loads, and comparing their mortality in later
      epidemics. Under functional trans-generational response mechanisms, we expect
      that those who were conceived under high pathogenic stress load will have
      relatively low mortality during a later epidemic. METHODS: We use data from the
      Registre de la Population du Quebec Ancien, which covers the historical
      population living in St. Lawrence Valley, Quebec, Canada. Children born in 1705
      1724 were grouped according to their exposure during conception to the measles
      1714-15 epidemic. The 1714-15 epidemic was followed by two mortality crises in
      1729-1734. The cause of the first crises in 1729 is not exactly known. The second
      crisis in 1732 was caused by a smallpox epidemic. Using proportional hazard Cox
      regression models with multivariate adjustment and with fixed-effects approach
      that compare siblings, we analyze whether mortality in 1729-1734 is affected by
      exposure to the 1714-15 epidemic. RESULTS: Children who were conceived during the
      peak of the measles epidemic of 1714-15 exhibited significantly lower mortality
      during the 1729-1734 crisis than those who were born before the 1714-15 epidemic
      (mortality hazard ratio 0.106, p<.05 in multivariate adjusted models; 0.142 p<.1
      in sibling comparison models). CONCLUSIONS: The results are consistent with a
      trans-generational mechanism that functionally responds to pathogen stress and
      suggest that early disease exposure may be protective later in life. Alternative
      explanations for the mortality patterns are discussed and shown to be
      problematic.

PMID- 24739874
TI  - Multi-kinase inhibitor C1 triggers mitotic catastrophe of glioma stem cells
      mainly through MELK kinase inhibition.
AB  - Glioblastoma multiforme (GBM) is a highly lethal brain tumor. Due to resistance
      to current therapies, patient prognosis remains poor and development of novel and
      effective GBM therapy is crucial. Glioma stem cells (GSCs) have gained attention
      as a therapeutic target in GBM due to their relative resistance to current
      therapies and potent tumor-initiating ability. Previously, we identified that the
      mitotic kinase maternal embryonic leucine-zipper kinase (MELK) is highly
      expressed in GBM tissues, specifically in GSCs, and its expression is inversely
      correlated with the post-surgical survival period of GBM patients. In addition,
      patient-derived GSCs depend on MELK for their survival and growth both in vitro
      and in vivo. Here, we demonstrate evidence that the role of MELK in the GSC
      survival is specifically dependent on its kinase activity. With in silico
      structure-based analysis for protein-compound interaction, we identified the
      small molecule Compound 1 (C1) is predicted to bind to the kinase-active site of
      MELK protein. Elimination of MELK kinase activity was confirmed by in vitro
      kinase assay in nano-molar concentrations. When patient-derived GSCs were treated
      with C1, they underwent mitotic arrest and subsequent cellular apoptosis in
      vitro, a phenotype identical to that observed with shRNA-mediated MELK knockdown.
      In addition, C1 treatment strongly induced tumor cell apoptosis in slice cultures
      of GBM surgical specimens and attenuated growth of mouse intracranial tumors
      derived from GSCs in a dose-dependent manner. Lastly, C1 treatment sensitizes
      GSCs to radiation treatment. Collectively, these data indicate that targeting
      MELK kinase activity is a promising approach to attenuate GBM growth by
      eliminating GSCs in tumors. 

PMID- 24739875
TI  - Effects of insulin detemir and NPH insulin on body weight and appetite-regulating
      brain regions in human type 1 diabetes: a randomized controlled trial.
AB  - Studies in rodents have demonstrated that insulin in the central nervous system
      induces satiety. In humans, these effects are less well established. Insulin
      detemir is a basal insulin analog that causes less weight gain than other basal
      insulin formulations, including the current standard intermediate-long acting
      Neutral Protamine Hagedorn (NPH) insulin. Due to its structural modifications,
      which render the molecule more lipophilic, it was proposed that insulin detemir
      enters the brain more readily than other insulins. The aim of this study was to
      investigate whether insulin detemir treatment differentially modifies brain
      activation in response to food stimuli as compared to NPH insulin. In addition,
      cerebral spinal fluid (CSF) insulin levels were measured after both treatments.
      Brain responses to viewing food and non-food pictures were measured using
      functional Magnetic Resonance Imaging in 32 type 1 diabetic patients, after each
      of two 12-week treatment periods with insulin detemir and NPH insulin,
      respectively, both combined with prandial insulin aspart. CSF insulin levels were
      determined in a subgroup. Insulin detemir decreased body weight by 0.8 kg and NPH
      insulin increased weight by 0.5 kg (p = 0.02 for difference), while both
      treatments resulted in similar glycemic control. After treatment with insulin
      detemir, as compared to NPH insulin, brain activation was significantly lower in
      bilateral insula in response to visual food stimuli, compared to NPH (p = 0.02
      for right and p = 0.05 for left insula). Also, CSF insulin levels were higher
      compared to those with NPH insulin treatment (p = 0.003). Our findings support
      the hypothesis that in type 1 diabetic patients, the weight sparing effect of
      insulin detemir may be mediated by its enhanced action on the central nervous
      system, resulting in blunted activation in bilateral insula, an appetite
      regulating brain region, in response to food stimuli. TRIAL REGISTRATION:
      ClinicalTrials.gov NCT00626080.

PMID- 24739877
TI  - Associations between individual-level social capital and self-rated health or
      depression among elderly men and women.
AB  - OBJECTIVES: Recent studies have investigated the relationship between social
      capital and health, although relatively few studies have evaluated the role of
      gender in this relationship. This study's aim was to investigate whether
      individual-level social capital in communities is associated with the self
      reported health (self-rated health and depression) of urban elderly women and men
      living at home, even after adjusting for some confounding factors, and whether
      there is a gender difference in the association between social capital and
      health. METHODS: A self-administered questionnaire was mailed to 2,400 people
      aged between 65 and 79 who were not receiving long-term care insurance services
      in City A (Tokyo). Indicators of social capital, as represented by cognitive
      social capital (trust in neighbors and reciprocity) and structural social capital
      (group membership in local associations), were tested with two self-reported
      health indicators: perceived health and depression. The associations between
      social capital and perceptions of health were analyzed for men and women
      respectively using multivariate logistic regression analysis with adjustments
      made for age, economic status, educational status, presence of chronic disorders,
      functional capability levels, marital status, and duration of residence. RESULTS:
      The number of valid responses was 1,776 (men: n=887, 71.2 +/- 4.0 years; women:
      n=889, 70.9 +/- 3.9 years; mean +/- SD) with a response rate of 74.5%. Lower
      levels of cognitive social capital (civic mistrust) were associated with an odds
      ratio for poorer self-rated health of 1.58 (95% CI [1.07-2.34], P=.022) at the
      individual level in men. In women, lack of reciprocity (OR=1.63, 95% CI [1.10
      2.41], P=.014) was associated with poorer self-rated health. Civic mistrust and
      lack of reciprocity were associated with depression in men and women. Lack of
      group membership in local associations was associated with self-rated health
      (OR=1.68, 95% CI [1.16-2.44], P=.007) and depression (OR=2.24, 95% CI [1.49
      3.38], P<.001) in women. CONCLUSION: Civic mistrust was associated with poorer
      self-rated health and a lack of reciprocity was associated with depression in
      men. In women, lack of reciprocity was associated with poorer self-rated health
      and depression, and lack of group membership in local associations was associated
      with self-rated health and depression. These results lead to the conclusion that
      there were noticeable gender differences in the relationship between the social
      capital and self-rated health of the elderly. A longitudinal study should be
      conducted to clarify the causal relationship between social capital and perceived
      health.

PMID- 24739876
TI  - Exploring the influence of EGCG on the beta-sheet-rich oligomers of human islet
      amyloid polypeptide (hIAPP1-37) and identifying its possible binding sites from
      molecular dynamics simulation.
AB  - EGCG possesses the ability of disaggregating the existing amyloid fibrils which
      were associated with many age-related degenerative diseases. However, the
      molecular mechanism of EGCG to disaggregate these fibrils is poorly known. In
      this work, to study the influence of EGCG on the full-length human islet amyloid
      polypeptide 1-37 (hIAPP1-37) oligomers, molecular dynamics simulations of hIAPP1
      37 pentamer and decamer with EGCG were performed, respectively. The obtained
      results indicate that EGCG indeed destabilized the hIAPP1-37 oligomers. The
      nematic order parameter and secondary structure calculations coupled with the
      free-energy landscape indicate that EGCG broke the initial ordered pattern of two
      polymers, greatly reduced their beta-sheet content and enlarged their
      conformational space. On this basis, three possible target sites were identified
      with the binding capacity order of S1>S2>S3. After a deeper analysis of each
      site, we found that S1 was the most possible site on which residues B
      Ile26/Ala25, A-Phe23, B/C-Leu27 and E-Tyr37 played an important role for their
      binding. The proposal of this molecular mechanism can not only provide a
      prospective interaction figure between EGCG and beta-sheet-rich fibrils of hIAPP1
      37, but also is useful for further discovering other potential inhibitors. 

PMID- 24739878
TI  - The longitudinal change in physical activity among Great East Japan Earthquake
      victims living in temporary housing.
AB  - OBJECTIVES: This study investigated the longitudinal changes in the physical
      activity of the Great East Japan Earthquake victims living in temporary housing.
      METHODS: Thirty-nine residents (10 men and 29 women) living in temporary housing
      in Kamaishi City, Iwate Prefecture, participated in a health survey in 2012.
      Among these residents, 31 who also participated in a health survey in 2011 were
      included in a longitudinal study of physical activity. The physical activity for
      two weeks after the health survey was measured using a tri-accelerometer.
      RESULTS: During the one-year period from 2011 to 2012, the median daily step
      counts changed from 4,959 (interquartile range: 2,910-6,029) steps/day to 4,618
      (interquartile range: 3,007-7,123) steps/day. The step counts increased for 18
      people (56%). The amount of moderate to vigorous physical activity changed from
      13.3 (interquartile range: 7.7-22.4) METs h/week to 16.1 (interquartile range:
      6.3-25.2) METs h/week. An increase in daily step counts occurred for 14 out of 21
      subjects who were <65 years old (67%) and only 3 out of 10 subjects who were >=65
      years old (30%). CONCLUSION: It was suggested that physical activity levels
      increased because the interquartile range of step counts moved in the direction
      of an increase and the median amount of moderate to vigorous physical activity
      increased. However, increasing support for physical activity in the future is
      required because the physical activity levels of the Great East Japan Earthquake
      victims who were living in temporary housing were still low compared to the
      national and regional averages.

PMID- 24739879
TI  - How do pediatricians in Japanese hospitals introduce welfare services to families
      who have children with disabilities?

PMID- 24739880
TI  - Tentative food defense guidelines for food producers and processors in Japan.
AB  - OBJECTIVES: With increasing global interest in intentional food contamination,
      expert meetings have been held by the G8, while the U.S. government has proposed
      policies for preventing food terrorism and intentional contamination. However,
      Japan has no food defense policy, and some food companies are concerned about an
      impending terrorism and contamination crisis. METHODS: We developed a Food
      Defense Checklist for Food Producers and Processors and published the details on
      the website. We also developed tentative Food Defense Guidelines for Food
      Producers and Processors on the basis of the checklist. In this study, we tested
      the usability of the guidelines through a hearing survey regarding food plants.
      We also compared the checklist with the implementation manual for the approval
      system of Comprehensive Sanitation Management and Production Process (the
      Japanese equivalent of the HACCP). RESULTS: We organized the comments gleaned
      from the hearing survey and provided a detailed explanation of the guidelines. As
      the HACCP has been adopted by Japanese food companies, we included both
      precautionary measures and the HACCP perspective in the explanation regarding the
      rapid dissemination of information. CONCLUSION: The guidelines are useful for
      Japanese food companies, and it is important to disseminate knowledge on this
      topic and implement food defense measures.

PMID- 24739881
TI  - Subchronic toxicological study of two artemisinin derivatives in dogs.
AB  - The objective of our study was to profile and compare the systematic changes
      between orally administered artesunate and intramuscularly injected artemether at
      a low dose over a 3-month period (92 consecutive days) in dogs. Intramuscular
      administration of 6 mg kg-1 artemether induced a decreased red blood cell (RBC)
      count (anemia), concurrent extramedullary hematopoiesis in the spleen and
      inhibition of erythropoiesis in the bone marrow. We also observed a prolonged QT
      interval and neuropathic changes in the central nervous system, which
      demonstrated the cortex and motor neuron vulnerability, but no behavioral
      changes. Following treatment with artesunate, we observed a decreased heart rate,
      which was most likely due to cardiac conduction system damage, as well as a
      deceased RBC count, extramedullary hematopoiesis in the spleen and inhibition of
      erythropoiesis in the bone marrow. However, in contrast to treatment with
      artemether, neurotoxicity was not observed following treatment with artesunate.
      In addition, ultra-structural examination by transmission electron microscopy
      showed mitochondrial damage following treatment with artesunate. These findings
      demonstrated the spectrum of toxic changes that result upon treatment with
      artesunate and artemether and show that the prolonged administration of low doses
      of these derivatives result in diverse toxicity profiles. 

PMID- 24739882
TI  - Gene replacement in Mycobacterium chelonae: application to the construction of
      porin knock-out mutants.
AB  - Mycobacterium chelonae is a rapidly growing mycobacterial opportunistic pathogen
      closely related to Mycobacterium abscessus that causes cornea, skin and soft
      tissue infections in humans. Although M. chelonae and the emerging mycobacterial
      pathogen M. abscessus have long been considered to belong to the same species,
      these two microorganisms considerably differ in terms of optimum growth
      temperature, drug susceptibility, pathogenicity and the types of infection they
      cause. The whole genome sequencing of clinical isolates of M. chelonae and M.
      abscessus is opening the way to comparative studies aimed at understanding the
      biology of these pathogens and elucidating the molecular bases of their
      pathogenicity and biocide resistance. Key to the validation of the numerous
      hypotheses that this approach will raise, however, is the availability of genetic
      tools allowing for the expression and targeted mutagenesis of genes in these
      species. While homologous recombination systems have recently been described for
      M. abscessus, genetic tools are lacking for M. chelonae. We here show that two
      different allelic replacement methods, one based on mycobacteriophage-encoded
      recombinases and the other on a temperature-sensitive plasmid harboring the
      counterselectable marker sacB, can be used to efficiently disrupt genes in this
      species. Knock-out mutants for each of the three porin genes of M. chelonae ATCC
      35752 were constructed using both methodologies, one of which displays a
      significantly reduced glucose uptake rate consistent with decreased porin
      expression. 

PMID- 24739884
TI  - Potentially avoidable hospital admissions in Germany: an analysis of factors
      influencing rates of ambulatory care sensitive hospitalizations.
AB  - BACKGROUND: The concept of ambulatory care sensitive hospitalization (ACSH) is
      based on the assumption that hospitalization for certain conditions might have
      been avoided by the timely provision of appropriate care outside the hospital. As
      preventive care and early treatment are often carried out in the ambulatory
      setting, ACSH have come to be viewed as an indicator of quality for this sector
      of the health-care system. METHOD: Factors potentially influencing the regional
      distribution of ACSH were examined for four conditions-congestive heart failure,
      angina pectoris, arterial hypertension, and diabetes mellitus-with separate
      analyses for men and women. A regression analysis was performed on the basis of
      German nationwide data for the year 2008 (hospital statistics and population
      statistics). The data covered all areas of Germany. RESULTS: Each rise in the
      density of practice based specialists by 1 per 100,000 inhabitants was associated
      with a 0.1% reduction of ACSH in general and with a 0.3% reduction of ACSH for
      diabetes among men. A corresponding rise in the density of general practitioners
      was associated with reductions of ACSH among men by 0.1% for heart failure and by
      0.5% for hypertension, yet also with increases of ACSH for angina pectoris (0.2%
      rise) and for diabetes (0.4% rise). Unemployment, residency in a rural area, and
      the number of hospital beds available locally were all positively correlated with
      small rises the ACSH rate. An age of 65 years and older was associated with the
      highest ACSH rates (0.7% to 3.6%). CONCLUSION: Overall, the analyzed variables
      were only weakly associated with the frequency of ambulatory care sensitive
      hospitalization. Future studies should consider further aspects such as the
      quality of care, comorbidities, and participation in healthcare programs.

PMID- 24739883
TI  - Stiffness-activated GEF-H1 expression exacerbates LPS-induced lung inflammation.
AB  - Acute lung injury (ALI) is accompanied by decreased lung compliance. However, a
      role of tissue mechanics in modulation of inflammation remains unclear. We
      hypothesized that bacterial lipopolysacharide (LPS) stimulates extracellular
      matrix (ECM) production and vascular stiffening leading to stiffness-dependent
      exacerbation of endothelial cell (EC) inflammatory activation and lung barrier
      dysfunction. Expression of GEF-H1, ICAM-1, VCAM-1, ECM proteins fibronectin and
      collagen, lysyl oxidase (LOX) activity, interleukin-8 and activation of Rho
      signaling were analyzed in lung samples and pulmonary EC grown on soft (1.5 or
      2.8 kPa) and stiff (40 kPa) substrates. LPS induced EC inflammatory activation
      accompanied by expression of ECM proteins, increase in LOX activity, and
      activation of Rho signaling. These effects were augmented in EC grown on stiff
      substrate. Stiffness-dependent enhancement of inflammation was associated with
      increased expression of Rho activator, GEF-H1. Inhibition of ECM crosslinking and
      stiffening by LOX suppression reduced EC inflammatory activation and GEF-H1
      expression in response to LPS. In vivo, LOX inhibition attenuated LPS-induced
      expression of GEF-H1 and lung dysfunction. These findings present a novel
      mechanism of stiffness-dependent exacerbation of vascular inflammation and
      escalation of ALI via stimulation of GEF-H1-Rho pathway. This pathway represents
      a fundamental mechanism of positive feedback regulation of inflammation.

PMID- 24739885
TI  - Quality of life rated too negatively.

PMID- 24739886
TI  - In reply.

PMID- 24739887
TI  - The differential diagnosis and treatment of tremor.
AB  - BACKGROUND: Essential tremor is the most common type of tremor, with a prevalence
      of 0.4% in the overall population and 4-7% in persons over age 65. In general,
      tremor is so common that patients with tremor are frequently treated not only by
      neurologists, but also by physicians from other specialties. METHOD: This review
      is based on publications retrieved by a selective PubMed search and on guidelines
      from Germany and abroad. RESULTS: Particular tremor syndromes are usually
      diagnosed on the basis of their typical clinical presentation and whatever
      accompanying manifestations may be present. Ancillary tests are usually
      unnecessary. Unilateral rest tremor accompanied by rigidity and bradykinesia is
      typical of Parkinson's disease. Essential tremor is a bilateral postural tremor.
      The most common cause of intention tremor is multiple sclerosis. Mild tremor
      syndromes can often be treated satisfactorily with drugs. In case of severe
      tremor, which is rarer, a stereotactic operation can be considered. The usual
      outcome of such procedures is the complete suppression of tremor. CONCLUSION:
      Most patients with tremor can be given a precise diagnosis and offered specific
      treatment. It is important for the physician to inform the patient about the
      expected course of tremor over time, its possible genetic causes, and the various
      available treatments.

PMID- 24739888
TI  - Bias reduction in calculation of inpatient fall rates.
AB  - Inpatient falls are the most common adverse hospital events. Despite the
      recognized importance of reducing inpatient falls, tracking and reporting methods
      are inconsistent. Moreover, recommended methods and statistical tests for
      comparing rates are complicated. This article demonstrates how to calculate fall
      rates using 3 common methods, summarizes the advantages and disadvantages of each
      method, and recommends best practices. 

PMID- 24739889
TI  - Population genomic analyses based on 1 million SNPs in commercial egg layers.
AB  - Identifying signatures of selection can provide valuable insight about the genes
      or genomic regions that are or have been under selective pressure, which can lead
      to a better understanding of genotype-phenotype relationships. A common strategy
      for selection signature detection is to compare samples from several populations
      and search for genomic regions with outstanding genetic differentiation. Wright's
      fixation index, FST, is a useful index for evaluation of genetic differentiation
      between populations. The aim of this study was to detect selective signatures
      between different chicken groups based on SNP-wise FST calculation. A total of 96
      individuals of three commercial layer breeds and 14 non-commercial fancy breeds
      were genotyped with three different 600K SNP-chips. After filtering a total of 1
      million SNPs were available for FST calculation. Averages of FST values were
      calculated for overlapping windows. Comparisons of these were then conducted
      between commercial egg layers and non-commercial fancy breeds, as well as between
      white egg layers and brown egg layers. Comparing non-commercial and commercial
      breeds resulted in the detection of 630 selective signatures, while 656 selective
      signatures were detected in the comparison between the commercial egg-layer
      breeds. Annotation of selection signature regions revealed various genes
      corresponding to productions traits, for which layer breeds were selected. Among
      them were NCOA1, SREBF2 and RALGAPA1 associated with reproductive traits,
      broodiness and egg production. Furthermore, several of the detected genes were
      associated with growth and carcass traits, including POMC, PRKAB2, SPP1, IGF2,
      CAPN1, TGFb2 and IGFBP2. Our approach demonstrates that including different
      populations with a specific breeding history can provide a unique opportunity for
      a better understanding of farm animal selection. 

PMID- 24739891
TI  - Ackerman's Tumor.

PMID- 24739890
TI  - Knowledge, attitudes and behaviour of hospital health-care workers regarding
      influenza A/H1N1: a cross sectional survey.
AB  - BACKGROUND: To assess the knowledge, the attitudes, and the behaviour towards
      influenza A/H1N1 and the vaccination among health-care workers (HCWs). METHODS: A
      sample of HCWs was selected from a random sample of non-teaching public
      hospitals, located in the cities of Naples and Avellino (Italy), received a self
      administered anonymous questionnaire including questions about socio-demographic
      characteristics, knowledge on modes of transmission and preventative measures,
      attitudes and behaviour relating to influenza A/H1N1. RESULTS: Only 36.1%
      correctly knew the main modes of transmission, and that HCWs are a risk category
      and this level of knowledge was significantly higher in HCWs having received
      information through scientific journals. A higher perceived risk of contracting
      influenza A/H1N1 has been observed in the HCWs more knowledgeable, in those
      considering influenza A/H1N1 a serious disease, and in those working in surgical
      wards. Only 16.7% have received the influenza A/H1N1 vaccination and HCWs with
      more fear of contracting influenza A/H1N1, those considering vaccine more useful
      and less dangerous were more likely to receive vaccine. CONCLUSIONS: Education
      and communication strategies for improving the level of knowledge and for the
      immunization uptake regarding influenza A/H1N1 HCWs are strongly needed.

PMID- 24739892
TI  - Ecosystem services in sustainable groundwater management.
AB  - The ecosystem services concept seems to get foothold in environmental policy and
      management in Europe and, for instance, The Netherlands. With respect to
      groundwater management there is a challenge to incorporate this concept in such a
      way that it contributes to the sustainability of decisions. Groundwater is of
      vital importance to societies, which is reflected in the presented overview of
      groundwater related ecosystem services. Classifications of these services vary
      depending on the purpose of the listing (valuation, protection, mapping et
      cetera). Though the scientific basis is developing, the knowledge-availability
      still can be a critical factor in decision making based upon ecosystem services.
      The examples in this article illustrate that awareness of the value of
      groundwater can result in balanced decisions with respect to the use of ecosystem
      services. The ecosystem services concept contributes to this awareness and
      enhances the visibility of the groundwater functions in the decision making
      process. The success of the ecosystem services concept and its contribution to
      sustainable groundwater management will, however, largely depend on other aspects
      than the concept itself. Local and actual circumstances, policy ambitions and
      knowledge availability will play an important role. Solutions can be considered
      more sustainable when more of the key elements for sustainable groundwater
      management, as defined in this article, are fully used and the presented
      guidelines for long term use of ecosystem services are respected. 

PMID- 24739893
TI  - Re: Knapp DW, Peer WA, Conteh A, Diggs AR, Cooper BR, Glickman NW, et al.
      detection of herbicides in the urine of pet dogs following home lawn application.
      Sci Total Env 2013; 456-457: 34-41.

PMID- 24739894
TI  - Risk-based prioritization of ground water threatening point sources at catchment
      and regional scales.
AB  - Contaminated sites threaten ground water resources all over the world. The
      available resources for investigation and remediation are limited compared to the
      scope of the problem, so prioritization is crucial to ensure that resources are
      allocated to the sites posing the greatest risk. A flexible framework has been
      developed to enable a systematic and transparent risk assessment and
      prioritization of contaminant point sources, considering the local, catchment, or
      regional scales (Danish EPA, 2011, 2012). The framework has been tested in
      several catchments in Denmark with different challenges and needs, and two of
      these are presented. Based on the lessons learned, the Danish EPA has prepared a
      handbook to guide the user through the steps in a risk-based prioritization
      (Danish EPA, 2012). It provides guidance on prioritization both in an
      administratively defined area such as a Danish Region, and within the bounds of a
      specified ground water catchment. The handbook presents several approaches in
      order to prevent the prioritization from foundering because of a lack of data or
      an inappropriate level of complexity. The developed prioritization tools,
      possible graphical presentation and use of the results are presented using the
      case studies as examples. The methodology was developed by a broad industry group
      including the Danish EPA, the Danish Regions, the Danish Nature Agency, the
      Technical University of Denmark, and consultants - and the framework has been
      widely accepted by the professional community in Denmark. The concepts are quite
      general and can be applied in other countries facing similar challenges. 

PMID- 24739895
TI  - Targeting EGFR in colorectal cancer: beyond KRAS exon 2.

PMID- 24739896
TI  - Panitumumab versus cetuximab in patients with chemotherapy-refractory wild-type
      KRAS exon 2 metastatic colorectal cancer (ASPECCT): a randomised, multicentre,
      open-label, non-inferiority phase 3 study.
AB  - BACKGROUND: The anti-EGFR monoclonal antibodies panitumumab and cetuximab are
      effective in patients with chemotherapy-refractory wild-type KRAS exon 2
      metastatic colorectal cancer. We assessed the efficacy and toxicity of
      panitumumab versus cetuximab in these patients. METHODS: For this randomised,
      open-label, phase 3 head-to-head study, we enrolled patients (from centres in
      North America, South America, Europe, Asia, Africa, and Australia) aged 18 years
      or older with chemotherapy-refractory metastatic colorectal cancer, an Eastern
      Cooperative Oncology Group (ECOG) performance status of 2 or less, and wild-type
      KRAS exon 2 status. Using a computer-generated randomisation sequence, we
      assigned patients (1:1; stratified by geographical region and ECOG performance
      status, with a permuted block method) to receive panitumumab (6 mg/kg once every
      2 weeks) or cetuximab (initial dose 400 mg/m(2); 250 mg/m(2) once a week
      thereafter). The primary endpoint was overall survival assessed for non
      inferiority (retention of >= 50% of the cetuximab treatment effect; historical
      hazard ratio [HR] for cetuximab plus best supportive care vs best supportive care
      alone of 0.55). The primary analysis included patients who received one or more
      dose of panitumumab or cetuximab, analysed per allocated treatment. Recruitment
      for this trial is closed. The trial is registered with ClinicalTrials.gov, number
      NCT01001377. FINDINGS: Between Feb 2, 2010, and July 19, 2012, we enrolled and
      randomly allocated 1010 patients, 999 of whom began study treatment: 499 received
      panitumumab and 500 received cetuximab. For the primary analysis of overall
      survival, panitumumab was non-inferior to cetuximab (Z score -3.19; p=0.0007).
      Median overall survival was 10.4 months (95% CI 9.4-11.6) with panitumumab and
      10.0 months (9.3-11.0) with cetuximab (HR 0.97; 95% CI 0.84-1.11). Panitumumab
      retained 105.7% (81.9-129.5) of the effect of cetuximab on overall survival seen
      in this study. The incidence of adverse events of any grade and grade 3-4 was
      similar across treatment groups. Grade 3-4 skin toxicity occurred in 62 (13%)
      patients given panitumumab and 48 (10%) patients given cetuximab. The occurrence
      of grade 3-4 infusion reactions was lower with panitumumab than with cetuximab
      (one [<0.5%] patient vs nine [2%] patients), and the occurrence of grade 3-4
      hypomagnesaemia was higher in the panitumumab group (35 [7%] vs 13 [3%]). We
      recorded one treatment-related fatal adverse event: a lung infection in a patient
      given cetuximab. INTERPRETATION: Our findings show that panitumumab is non
      inferior to cetuximab and that these agents provide similar overall survival
      benefit in this population of patients. Both agents had toxicity profiles that
      were to be expected. In view of the consistency in efficacy and toxicity seen,
      small but meaningful differences in the rate of grade 3-4 infusion reactions and
      differences in dose scheduling can guide physician choice of anti-EGFR treatment.

PMID- 24739898
TI  - Anti-androgen monotherapy for metastatic prostate cancer.

PMID- 24739897
TI  - Enzalutamide monotherapy in hormone-naive prostate cancer: primary analysis of an
      open-label, single-arm, phase 2 study.
AB  - BACKGROUND: The androgen receptor inhibitor enzalutamide is approved for the
      treatment of metastatic castration-resistant prostate cancer that has progressed
      on docetaxel. Our aim was to assess the activity and safety of enzalutamide
      monotherapy in men with hormone-naive prostate cancer. METHODS: This trial is an
      ongoing open-label, single-arm, phase 2 study, done across 12 European sites. Men
      aged over 18 years, with hormone-naive prostate cancer for whom hormone therapy
      was indicated, and who had non-castration levels of testosterone and prostate
      specific antigen (PSA) of 2 ng/mL or greater at screening, and an Eastern
      Cooperative Oncology Group score of 0, received oral enzalutamide 160 mg/day. The
      primary outcome was the proportion of patients with an 80% or greater decline in
      PSA at week 25. All analyses included all patients who had received at least one
      dose of the study drug. This study is registered with ClinicalTrials.gov, number
      NCT01302041. FINDINGS: 67 men were enrolled into the study. 62 patients (92.5%,
      95% CI 86.2-98.8) had a decline in PSA of 80% or greater at week 25. The most
      commonly reported treatment-emergent adverse events up to week 25 were
      gynaecomastia (n=24), fatigue (n=23), nipple pain (n=13), and hot flush (n=12),
      all of which were of mild to moderate severity. Nine patients had a treatment
      emergent adverse event of grade 3 or higher, most of which were reported in one
      patient each, except for pneumonia (grade 3, two patients) and hypertension
      (grade 3, four patients). Five patients reported serious adverse events, none of
      which were deemed to be treatment related. INTERPRETATION: Our findings suggest
      that enzalutamide monotherapy in men with hormone-naive prostate cancer of
      varying severity provides a level of disease suppression, and was generally well
      tolerated. These findings provide a rationale for further investigation of
      clinical response and outcomes with enzalutamide in non-castrate men with
      prostate cancer.

PMID- 24739899
TI  - Pneumoconiosis in dental technicians: HRCT and pulmonary function findings.
AB  - BACKGROUND: Pneumoconiosis is a form of diffuse interstitial lung disease, often
      resulting from occupational exposures. As dental prosthetic technicians (DPTs)
      build prostheses, they are exposed to many chemical materials that increase their
      risk of developing pneumoconiosis. AIMS: To document pulmonary function and
      prevalence of pneumoconiosis in DPTs. METHODS: A cross-sectional study of DPTs
      working in prosthetic laboratories who underwent pulmonary function test and high
      resolution chest computed tomography (HRCT) scanning. RESULTS: There were 76
      participants and pneumoconiosis was diagnosed in 46%. The most commonly seen
      radiological finding was round opacities, present in 38%. Agreement among HRCT
      readers was moderate to good. As defined by HRCT, emphysema was diagnosed more
      often in those with a longer occupational history or a history of smoking, and
      low carbon monoxide diffusion capacity (DLCO), but not in those with
      pneumoconiosis. Forced expiratory rate and DLCO were significantly lower in those
      who had worked 16 years or more (all P < 0.05). DLCO values were significantly
      lower in technicians with emphysema and in current smokers (all P < 0.01). Round
      opacities were also present in a substantial proportion of DPTs who had 15 years
      or less exposure. Because HRCT is able to detect radiological changes of
      occupational lung disease very early, the prevalence of pneumoconiosis in our
      participants was quite high. CONCLUSIONS: Pneumoconiosis identified by HRCT was
      present in almost half of DPTs surveyed. Appropriate education and workplace
      protection should be given to DPTs in order to prevent exposure to hazardous
      materials in dental prosthetics laboratories.

PMID- 24739901
TI  - Effects of different dietary energy and protein levels and sex on growth
      performance, carcass characteristics and meat quality of F1 Angus * Chinese
      Xiangxi yellow cattle.
AB  - BACKGROUND: The experiment evaluated the effect of nutrition levels and sex on
      the growth performance, carcass characteristics and meat quality of F1 Angus *
      Chinese Xiangxi yellow cattle. METHODS: During the background period of 184 d,23
      steers and 24 heifers were fed the same ration,then put into a 2 * 2 * 2
      factorial arrangement under two levels of - dietary energy (TDN: 70/80% DM),
      protein (CP: 11.9/14.3% DM) and sex (S: male/female) during the finishing phase
      of 146 d. The treatments were - (1) high energy/low protein (HELP), (2) high
      energy/high protein (HEHP), (3) low energy/low protein (LELP) and (4) low
      energy/high protein (LEHP). Each treatment used 6 steers and 6 heifers, except
      for HELP- 5 steers and 6 heifers. RESULTS: Growth rate and final carcass weight
      were unaffected by dietary energy and protein levels or by sex. Compared with the
      LE diet group, the HE group had significantly lower dry matter intake (DMI, 6.76
      vs. 7.48 kg DM/d), greater chest girth increments (46.1 vs. 36.8 cm), higher
      carcass fat (19.9 vs.16.3%) and intramuscular fat content (29.9 vs. 22.8% DM).
      The HE group also had improved yields of top and medium top grade commercial meat
      cuts (39.9 vs.36.5%). The dressing percentage was higher for the HP group than
      the LP group (53.4 vs. 54.9%). Steers had a greater length increment (9.0 vs. 8.3
      cm), but lower carcass fat content (16.8 vs. 19.4%) than heifers. The meat
      quality traits (shear force value, drip loss, cooking loss and water holding
      capacity) were not affected by treatments or sex, averaging 3.14 kg, 2.5, 31.5
      and 52.9%, respectively. The nutritive profiles (both fatty and amino acid
      composition) were not influenced by the energy or protein levels or by sex.
      CONCLUSIONS: The dietary energy and protein levels and sex significantly
      influenced the carcass characteristics and chemical composition of meat but not
      thegrowth performance, meat quality traits and nutritive profiles.

PMID- 24739900
TI  - Characterization of Withania somnifera leaf transcriptome and expression analysis
      of pathogenesis-related genes during salicylic acid signaling.
AB  - Withania somnifera (L.) Dunal is a valued medicinal plant with pharmaceutical
      applications. The present study was undertaken to analyze the salicylic acid
      induced leaf transcriptome of W. somnifera. A total of 45.6 million reads were
      generated and the de novo assembly yielded 73,523 transcript contig with average
      transcript contig length of 1620 bp. A total of 71,062 transcripts were annotated
      and 53,424 of them were assigned GO terms. Mapping of transcript contigs to
      biological pathways revealed presence of 182 pathways. Seventeen genes
      representing 12 pathogenesis-related (PR) families were mined from the
      transcriptome data and their pattern of expression post 17 and 36 hours of
      salicylic acid treatment was documented. The analysis revealed significant up
      regulation of all families of PR genes by 36 hours post treatment except WsPR10.
      The relative fold expression of transcripts ranged from 1 fold to 6,532 fold. The
      two families of peroxidases including the lignin-forming anionic peroxidase (WsL
      PRX) and suberization-associated anionic peroxidase (WsS-PRX) recorded maximum
      expression of 377 fold and 6532 fold respectively, while the expression of WsPR10
      was down-regulated by 14 fold. Additionally, the most stable reference gene for
      normalization of qRT-PCR data was also identified. The effect of SA on the
      accumulation of major secondary metabolites of W. somnifera including withanoside
      V, withaferin A and withanolide A was also analyzed and an increase in content of
      all the three metabolites were detected. This is the first report on expression
      patterns of PR genes during salicylic acid signaling in W. somnifera. 

PMID- 24739902
TI  - Epidermal RelA specifically restricts contact allergen-induced inflammation and
      apoptosis in skin.
AB  - Strong inhibition of NF-kappaB signaling in the epidermis results in spontaneous
      skin inflammation in mice and men. As there is evidence for linkage between
      polymorphisms within the NF-kappaB signaling pathway and human inflammatory skin
      phenotypes, we asked whether partial functional inhibition of NF-kappaB signaling
      in epidermal keratinocytes can modulate clinically relevant skin inflammation. We
      therefore mutated rela specifically in the epidermis of mice (RelA(E-MUT) mice).
      These mice show no inflammatory phenotype. Induction of contact allergy, but not
      croton oil-induced irritant dermatitis, resulted in stronger ear swelling and
      increased epidermal thickness in RelA(E-MUT) mice. Both contact allergen and
      croton oil treatment led to increased expression of calgranulins A and B
      (S100A8/A9) in RelA(E-MUT) mice. Epidermal hyperproliferation in RelA(E-MUT) mice
      was non-cell autonomous as cultured primary epidermal keratinocytes from RelA(E
      MUT) mice showed reduced proliferation compared with controls. These results
      demonstrate that epidermal RelA specifically regulates delayed-type
      hypersensitivity-induced skin inflammation. In addition, we describe here an
      essential but nonspecific function of RelA in the protection of epidermal
      keratinocytes from apoptosis. Our study identifies functions of NF-kappaB
      signaling in the epidermis and corroborates a specific role of epidermal
      keratinocytes in the regulation of skin inflammation.

PMID- 24739905
TI  - Life after brain death: Is the body still "alive"?

PMID- 24739903
TI  - Somatic mutation of GRIN2A in malignant melanoma results in loss of tumor
      suppressor activity via aberrant NMDAR complex formation.
AB  - The ionotropic glutamate receptors (N-methyl-D-aspartate receptors (NMDARs)) are
      composed of large complexes of multi-protein subunits creating ion channels in
      the cell plasma membranes that allow for influx or efflux of mono- or divalent
      cations (e.g., Ca(2+)) important for synaptic transmissions, cellular migration,
      and survival. Recently, we discovered the high prevalence of somatic mutations
      within one of the ionotropic glutamate receptors, GRIN2A, in malignant melanoma.
      Functional characterization of a subset of GRIN2A mutants demonstrated a loss of
      NMDAR complex formation between GRIN1 and GRIN2A, increased anchorage-independent
      growth in soft agar, and increased migration. Somatic mutation of GRIN2A results
      in a dominant negative effect inhibiting the tumor-suppressive phenotype of wild
      type (WT) GRIN2A in melanoma. Depletion of endogenous GRIN2A in melanoma cells
      expressing WT GRIN2A resulted in increased proliferation compared with control.
      In contrast, short-hairpin RNA depletion of GRIN2A in mutant cell lines slightly
      reduced proliferation. Our data show that somatic mutation of GRIN2A results in
      increased survival, and we demonstrate the functional importance of GRIN2A
      mutations in melanoma and the significance that ionotropic glutamate receptor
      signaling has in malignant melanoma.

PMID- 24739904
TI  - Retinitis pigmentosa, cutis laxa, and pseudoxanthoma elasticum-like skin
      manifestations associated with GGCX mutations.
AB  - Gamma-glutamyl carboxylase (GGCX) mutations have been reported in patients with a
      pseudoxanthoma elasticum (PXE)-like phenotype, loose redundant skin, and multiple
      vitamin K-dependent coagulation factor deficiencies. We report on the clinical
      findings and molecular results in 13 affected members of two families who had a
      uniform phenotype consisting of (PXE)-like skin manifestations in the neck and
      trunk, loose sagging skin of the trunk and upper limbs, and retinitis pigmentosa
      confirmed by electroretinographies in 10 affected individuals. There were no
      coagulation abnormalities. Molecular investigations of the ATP-binding cassette
      subfamily C member 6 did not yield causative mutations. All 13 affected family
      members were found to be homozygous for the splice-site mutation c.373+3G>T in
      the GGCX gene. All tested parents were heterozygous for the mutation, and healthy
      siblings were either heterozygous or had the wild type. We suggest that the
      present patients represent a hitherto unreported phenotype associated with GGCX
      mutations. Digenic inheritance has been suggested to explain the variability in
      phenotype in GGCX mutation carriers. Consequently, the present phenotype may not
      be explained only by the GGCX mutations only but may be influenced by variants in
      other genes or epigenetic and environmental factors. 

PMID- 24739906
TI  - Comparison of antimicrobial efficacy of chlorhexidine and combination mouth rinse
      in reducing the Mutans streptococcus count in plaque.
AB  - BACKGROUND: The removal of plaque is utmost important to control dental caries.
      But in children, factors like lack of dexterity, individual motivation and
      monitoring limit the effectiveness of tooth brushing. This necessitates the use
      of chemotherapeutic agents for control of plaque. AIMS: To compare the
      antimicrobial efficacy of 0.2% chlorhexidine mouth rinse and mouth rinse
      containing 0.03% triclosan, 0.05% sodium fluoride, and 5% xylitol in reducing the
      Mutans streptococcus count in plaque. MATERIALS AND METHODS: Thirty healthy
      children aged 8-10 years with dmft (decay component) of three or four were
      selected. They were divided randomly into two groups: The control or
      chlorhexidine group and the study group or combination mouth rinse. Both the
      groups practiced rinsing with respective mouth wash for 1 min for 15 d twice a
      day. The plaque samples were collected and after incubation Mutans streptococcus
      count was estimated on the strips from the Dentocult SM kit and evaluated using
      manufacture's chart. STATISTICAL ANALYSIS USED: Wilcoxon matched pairs signed
      ranks test and Mann-Whitney U test were used to analyze the findings. RESULTS:
      Statistically significant reduction in the Mutans streptococci count in the
      plaque was seen in the control and study group from baseline level. But when both
      the groups were compared, the antimicrobial effect of chlorhexidine was more.

PMID- 24739907
TI  - Knowledge and attitude of parents with regard to avulsed permanent tooth of their
      children and their emergency management--Chennai.
AB  - BACKGROUND: Dental avulsion is defined as the complete displacement of tooth out
      of socket along with severed periodontal ligament with or without fracture of the
      alveolar bone. Reimplantation of the avulsed tooth is considered as a best
      treatment modality due to its biological and psychological advantages. The
      viability of periodontal ligament cell on the root surface determines the
      prognosis of reimplanted tooth. The knowledge of parents regarding important
      steps to be taken immediately after dental avulsion is considered crucial for
      success of the treatment. AIM: The study was conducted to evaluate the knowledge
      and attitude of parents in Chennai with regard to avulsed permanent tooth of
      their children and their emergency management using a questionnaire. MATERIALS
      AND METHODS: The study included 529 parents who accompanied their children, aged
      between 6 years and 12 years, to the Department of Pedodontics, Saveetha Dental
      College and Hospitals. Chi-square test was done to evaluate the association
      between the results and the genders, educational level, and geographical status
      of the respondents. RESULTS: The study revealed even though 90.7% of parents knew
      that saving an avulsed permanent tooth is important, but almost one third of the
      population thought ice water was the best media to transport an avulsed teeth.
      CONCLUSION: There is an imperative need for educating the parents regarding
      management of avulsed tooth for which 87.9% showed interest.

PMID- 24739908
TI  - 'Metal to resin': a comparative evaluation of conventional band and loop space
      maintainer with the fiber reinforced composite resin space maintainer in
      children.
AB  - AIMS: To compare the clinical efficacy of two space maintainers namely,
      conventional band and loop and Fiber Reinforced Composite Resin (FRCR) space
      maintainers. SUBJECTS AND METHODS: Thirty healthy children, aged 5 to 8 years
      were selected having at least two deciduous molars in different quadrants
      indicated for extraction or lost previously. FRCR space maintainer was placed in
      one quadrant and in the other quadrant band and loop space maintainer was
      cemented. All the patients were recalled at 1 st, 3 rd, and 6 th months for
      evaluation of both types of space maintainer. Patient acceptability, time taken,
      and clinical efficacy was recorded. STATISTICAL ANALYSIS USED: The observations
      thus obtained were subjected to statistical analysis using Chi- square test and
      Mann-Whitney U test. RESULTS: Patient acceptability was greater in Group I (FRCR)
      in comparison to Group II (band and loop space maintainer). The time taken by
      Group I was significantly lower as compared to that of Group II. In Group I,
      debonding of enamel, composite was the most common complication leading to
      failure followed by debonding of fiber composite. In Group II, cement loss was
      the most common complication leading to failure followed by slippage of band and
      fracture of loop. The success rates of Groups I and Group II weares 63.3% and
      36.7%, respectively. CONCLUSION: The study concluded that FRCRFiber Reinforced
      Composite Resin (Ribbond) space maintainers can be considered as viable
      alternative to the conventional band and loop space maintainers.

PMID- 24739909
TI  - Utilization of free dental health care services provided to the perinatally
      infected human immunodeficiency virus children in Bangalore: longitudinal study.
AB  - BACKGROUND: Use of Highly active anti-retroviral therapy have increased the life
      expectancy of human immunodeficiency virus (HIV) infected patients and hence it
      is imperative that all efforts have to be made by Pediatric dentists to provide a
      better oral health for these children. AIM: The aim of this study was to evaluate
      the rate of utilization of free dental treatment provided to these perinatally
      infected HIV positive children who were previously screened as a part of oral
      health survey. DESIGN: Purposive sampling was used. INCLUSION CRITERIA:
      Perinatally infected HIV children screened for oral health status. EXCLUSION
      CRITERIA: Patients not screened during the oral health survey. MATERIALS AND
      METHODS: Attendance records of 319 perinatally HIV infected children consisting
      of 178 males and 141 females attending a specialized pediatric outpatient clinic
      at Indira Gandhi Institute of Child Health were examined to compare treatment
      compliance rates. RESULTS: The number of patients in the severe category who
      completed treatment was significantly less compared with mild and advanced
      categories (P < 0.001). The difference in the proportion of patients who
      completed treatment between mild and advanced group was not statistically
      significant (P > 0.05). CONCLUSION: The results show that children with HIV have
      significantly lower compliance. Even though all dental treatment provided to them
      was free of the cost it still had no impetus to encourage them to go through with
      the treatment.

PMID- 24739910
TI  - The antimicrobial effectiveness of 25% propolis extract in root canal irrigation
      of primary teeth.
AB  - CONTEXT: The choice of irrigating solution used in root canals of primary teeth
      is complicated by their complex morphology and paucity of associated literature.
      Propolis is a natural product that has gained interest in this context due to its
      antibacterial effectiveness against several endodontic pathogens. AIM: The
      present study was undertaken to assess the potential of water-soluble 25%
      propolis extract against microorganisms present in root canals of primary teeth
      during endodontic procedures. SETTINGS AND DESIGN: The child patients in the age
      group of 4-7 years with radiographic evidence of carious pulp exposure were
      included in the study. Definitive selection was done after gaining access into
      the pulp chamber and root canals of the selected teeth. The clinical and
      radiographic evidence of pathosis was ruled out for inclusion in the study.
      MATERIALS AND METHODS: The selected teeth were divided into two groups randomly.
      In Group A 0.9% isotonic saline and in Group B 25% extract water-soluble propolis
      were used as irrigating solution, respectively. The bacterial samples were
      collected both pre- and post-irrigation and were transferred for microbial assay.
      STAISTISTICAL ANALYSIS: Wilcoxon matched signed rank test was used to compare the
      pre-and post-irrigation bacterial counts. Mann-Whitney test was used to compare
      the mean change (pre-post) in bacterial colony counts of groups in the study.
      RESULTS: Antimicrobial effectiveness of 25% water-soluble extract of propolis in
      the root canals of primary teeth was confirmed in the present study. The
      reduction in the mean bacterial colony counts of all the isolated bacteria was
      noticed higher in Group B than Group A. CONCLUSION: The results of the present
      study have confirmed that the antibacterial effectiveness of water-soluble
      extract of propolis in the root canals of primary teeth in vivo. Considering the
      low toxicity concerns and antibacterial effectiveness, water-soluble extract of
      25% propolis can be advocated as a root canal irrigant in endodontic treatment of
      primary teeth.

PMID- 24739911
TI  - Oral health status of Tibetan and local school children of Kushalnagar, Mysore
      district, India: a comparative study.
AB  - The presence of migrants culturally different from inhabitants of the host
      country is now a widespread phenomenon. It is known that dietary habits and oral
      hygiene practices vary from country to country, which in turn has a profound
      effect on oral health. OBJECTIVES: To assess and compare the oral health status
      of Tibetan school children and local school children of Kushalnagar (Bylakuppe).
      STUDY DESIGN: A survey was conducted at Kushalnagar (Bylakuppe), in Mysore
      district, India to assess the oral health status of Tibetan school children (n =
      300) and local school children (n = 300) and compared using World Health
      Organization oral health proforma (1997). RESULTS: The proportional values are
      compared using chi-square test and the mean values are compared using Student's t
      test. Statistically significant results were obtained for soft tissue lesions,
      dental caries, malocclusion, and treatment needs. However, results were not
      significant when gingivitis was compared in the two populations. CONCLUSIONS:
      Tibetan school children showed higher prevalence of Angular cheilitis, gingival
      bleeding, dental caries experience, malocclusion, and treatment needs in
      comparison with non-Tibetans. Among the Tibetan school children, the requirement
      for two or more surface filling was more.

PMID- 24739912
TI  - Analysis of microleakage of temporary restorative materials in primary teeth.
AB  - AIM: The aim of this study was to compare the coronal microleakage of restorative
      materials used between sessions of endodontic treatment in primary teeth.
      MATERIALS AND METHODS: Forty healthy primary canines were chosen and randomly
      allocated to four groups: Group 1 - Cimpat Branco (r) (n = 10), Group 2 - Bioplic
      (r) (n = 10), Group 3 - Maxxion R (r) glass ionomer cement (n = 10), and Group 4
      (control) - Z350 (r) composite resin (n = 10). Class V cavities were created and
      fillings carried out following the manufacturer's instructions. The teeth were
      submitted to thermocycling, sealed, and immersed in 0.5% basic fuchsin solution
      for 24 h. The teeth were split along their long axis in the vestibulolingual
      direction and the tooth-restorative material interface was photographed. The
      percentage of microleakage was calculated using the ImageJ program. Data were
      analyzed using the analysis of variance (ANOVA) F-test and Bonferroni's t-test,
      with a 5% level of significance. RESULTS: The following mean percentages of
      microleakage were found: Group 1 = 16.08%, Group 2 = 46.98%, Group 3 = 47.93%,
      and Group 4 = 11.03%. Statistically, significant differences were found in the
      comparison of Groups 1 and 4 to Groups 2 and 3. CONCLUSION: Cimpat Branco (r) had
      a lower percentage of microleakage in comparison to Bioplic (r) and Maxxion R (r)
      glass ionomer cement.

PMID- 24739913
TI  - Oral health status and parental perception of child oral health related quality
      of-life of children with autism in Bangalore, India.
AB  - BACKGROUND: Children with autism present with the physical-mental impairments and
      oral problems, which may have an impact on their quality-of-life (QoL). The aim
      of the following study was to assess oral health status and parental perception
      of child oral health related quality of life (OHRQoL) among children with autism.
      MATERIALS AND METHODS: A cross-sectional study was conducted in 4-15-year-old
      children with autism (n = 135) and children without autism (n = 135). Oral health
      status was evaluated using Oral Hygiene Index-Simplified (OHI-S), its Miglani's
      modification for deciduous teeth, Decayed, missing and filled teeth (DMFT/dmft)
      and Decayed, missing and filled surface (DMFS/dmfs) indices. Parents answered the
      Parental-Caregivers Perception Questionnaire for assessing children's OHRQoL.
      Mann-Whitney U, Chi-square test and Pearson's correlation analysis were
      performed. RESULTS: Mean OHI-S, DMFT, dmft scores were significantly high among
      children with autism (2.07 +/- 0.83; 0.86 +/- 1.22, 1.40 +/- 2.48) when compared
      to children without autism (0.46 +/- 0.58; 0.46 +/- 1.06, 0.59 +/- 1.28)
      respectively. Out of all domains of OHRQoL, mean score of functional limitations
      related to teeth problem was significantly higher among children with autism
      (8.87 +/- 5.65) as compared to non-autism group (6.66 +/- 4.97). CONCLUSION:
      Functional limitations may have a negative impact on oral health status that
      might influence OHRQoL.

PMID- 24739914
TI  - Effect of polishing on the microleakage of three different restorative materials:
      an in vitro study.
AB  - AIMS AND OBJECTIVES: The purpose of this in vitro study was to investigate the
      effect of polishing systems on the microleakage of three different restorative
      materials (Ketac Molar Easymix, Ketac N100 and Filtek P90). MATERIALS AND
      METHODS: Class V cavities were prepared at the cemento-enamel junction of 60
      freshly extracted premolars. The prepared teeth were randomly divided into three
      groups and restored with the three materials. The restored teeth were stored in
      distilled water at 37 degrees C for 1 week. The restored teeth were then divided
      into two subgroups (polished and not polished) of 10. Finishing and polishing of
      the polished group was done using the Sof-Lex polishing system. Furthermore, all
      the restorations were subjected to dye penetration testing. RESULTS: Results
      showed that maximum microleakage was observed for the not polished group of
      Filtek P90 and least levels of microleakage were seen for the polished group of
      Ketac Molar Easymix. CONCLUSION: There was a significant difference seen when
      Ketac Molar Easymix was compared with Ketac N100 and Filtek P90 in terms of the
      extent of microleakage exhibited on polishing of the three materials; with the
      former exhibiting the least microleakage scores.

PMID- 24739915
TI  - Calcifying epithelial odontogenic tumor, a rare presentation in children: two
      case reports.
AB  - Calcifying epithelial odontogenic tumor (CEOT) is a rare and benign odontogenic
      neoplasm that affects the jaws. It is certainly an atypical instance to find this
      tumor in children. Here, we present two case reports of CEOT presenting in
      mandible of a 12- and 13-year-old female child, respectively. CEOT have been
      reported to show features of malignant transformation also. 

PMID- 24739916
TI  - Oro-facial-digital syndrome type 1: a case report.
AB  - Oro-Facial Digital Syndrome (OFDS) is a generic term for group of apparently
      distinctive genetic diseases that affect the development of the oral cavity,
      facial features, and digits. One of these is OFDS type I (OFDS-I) which has
      rarely been reported in Asian countries. This is the case report of a 13 year old
      patient with OFDS type I who reported to the Department of Pedodontics and
      Preventive Dentistry, with the complaint of discolored upper front teeth. 

PMID- 24739917
TI  - Polycarbonate crowns for primary teeth revisited: restorative options, technique
      and case reports.
AB  - Esthetics by definition is the science of beauty - that particular detail of an
      animate or inanimate object that makes it appealing to the eye. In the modern,
      civilized, and cosmetically conscious world, well-contoured and well-aligned
      white teeth set the standard for beauty. Such teeth are not only considered
      attractive but are also indicative of nutritional health, self esteem, hygienic
      pride, and economic status. Numerous treatment approaches have been proposed to
      address the esthetics and retention of restorations in primary teeth. Even though
      researchers have claimed that certain restorations are better than the others,
      particularly owing to the issues mentioned above, the search for the ideal
      esthetic restoration for the primary teeth continues. This paper revisits and
      attempts to reintroduce the full coverage restoration, namely, polycarbonate
      crown, for use in primary anterior teeth. 

PMID- 24739918
TI  - Seckel syndrome: a rare case report.
AB  - Seckel syndrome (SS) is a rare, autosomal recessive syndrome; characterized by
      severe intrauterine and postnatal growth retardation, microcephaly, mental
      retardation, and typical facial appearance with beaklike protrusion of the
      midface (bird headed). In addition to the characteristic craniofacial dysmorphism
      and skeletal defects, abnormalities have been described in the cardiovascular,
      hematopoietic, endocrine, gastrointestinal, and central nervous systems. Usually
      such patients have poor psychomotor development. This case report presents an 8
      year-old child with SS born to parents, exposed in Bhopal gas disaster. 

PMID- 24739919
TI  - Unusual facial pain secondary to inferior alveolar nerve compression caused by
      impacted mandibular second molar.
AB  - Symptoms of inferior alveolar nerve (IAN) compression are reported during
      endodontic procedures, placement of implants, third molar surgeries, inferior
      alveolar nerve block injections, trauma, orthognathic injuries, ablative
      surgeries or use of medicaments. Presented is a rare case of a 15-year-old girl
      who reported severe pain in relation to an impacted permanent mandibular left
      second molar, the roots of which had entrapped the mandibular canal causing
      compression of IAN. Timely surgical intervention and sectional removal of the
      impacted molar is indicated to relieve the symptoms and avoid permanent damage to
      the nerve. 

PMID- 24739920
TI  - Dental findings in patients with West syndrome: a report of two cases.
AB  - West syndrome a rare, severe form of epilepsy occurs in early infancy. It is
      characterized by a triad consisting of infantile spasms that occurs in clusters,
      arrest of psychomotor development and hypsarrhythmia on electroencephalogram. We
      present here two cases of west syndrome where patients required dental care due
      to the presence of certain dental findings. Preventive measurements such as
      controlled diet and proper oral hygiene along with professional dental management
      are recommended in patients with west syndrome to avoid dental problems. 

PMID- 24739921
TI  - Maturogenesis by revascularization in an infected immature permanent tooth.
AB  - Root canal treatment in teeth with incomplete root formation is a challenge. A
      case of maturogenesis in an immature infected tooth along with probable factors
      needed for success is discussed. Although clinical and radiographic evidence
      points to healing and root development, the long-term prognosis and the behavior
      of tissue occupying the canal space needs further investigation before the
      procedure can be adopted into routine clinical practice. 

PMID- 24739922
TI  - Esthetic improvement of white spot lesions and non-pitted fluorosis using resin
      infiltration technique: series of four clinical cases.
AB  - White opacities have always been a major concern of esthetics for patients and
      can have varying etiology. In general, white discolorations of enamel might be
      due to dental fluorosis, early caries (white spot lesions), developmental defects
      etc. Conventional treatment options available for such opacities include non
      invasive and invasive approaches. Recently, a new "micro-invasive" technique has
      been introduced as an alternative therapeutic approach that improves such
      opacities esthetically, in a single sitting, is painless and exhibits no
      complications. This case series illustrates the use of resin infiltration to
      treat fluorosis stains and WSLs, exhibiting significant improvement in esthetics.

PMID- 24739923
TI  - Hematological and surgical management in Glanzmann's thrombasthenia: a case
      report.
AB  - Glanzmann's thrombasthenia (GT) is a rare, congenital, and moderate to severe
      platelet disorder. The bleeding time is increased, due to lack of platelet
      aggregation, since the patients with GT have deficient or dysfunctional integrin
      membrane glycoproteins IIb and IIIa essential for platelet aggregation. Children
      with GT are mostly diagnosed very early in life due to the spontaneous and
      unexplained mucocutaneous bleeding. It is quite a challenging task when any
      surgery is indicated for children with GT. This case report is about the medical
      and surgical management of an 11-year-old girl diagnosed with Glannzmann's
      thrombasthenia who had to undergo a maxillary cyst enucleation. 

PMID- 24739924
TI  - Talon cusps in mandibular incisors: report of eight rare cases.
AB  - Talon cusps in mandibular anterior teeth are very rare. Talon cusps in mandibular
      anterior teeth associated with other anomalies are even rarer and that a
      bilateral case in the mandible has not been reported before. In this report,
      eight such rare cases of talon cusps in permanent mandibular incisors are
      presented. It includes a bilateral case that in the author's knowledge is the
      first case reported in the English literatures. 

PMID- 24739925
TI  - Autogenous tooth fragment reattachment: a multidisciplinary management for
      complicated crown-root fracture with biologic width violation.
AB  - Fractures of multiple permanent anterior teeth can be a traumatic experience for
      children, with functional, esthetic and psychological aspects. The treatment of
      complicated crown-root fractures (CRFs) is more challenging when the biologic
      width is violated. This paper presents a case of 12-year boy with complicated CRF
      of teeth #12 and #21, and horizontal crown fracture of tooth #11. It was managed
      by endodontic treatment, mucoperiosteal surgery with osteotomy to visualize the
      fracture line for fragment reattachment, followed by fiber-post placement and
      restoration with polycarbonate crowns. Clinical and radiographic evaluation after
      6 months was satisfactory with adequate functional and esthetic results. 

PMID- 24739926
TI  - Green synthesis of silver nanoparticles using Achillea biebersteinii flower
      extract and its anti-angiogenic properties in the rat aortic ring model.
AB  - Silver nanoparticles display unique physical and biological properties which have
      attracted intensive research interest because of their important medical
      applications. In this study silver nanoparticles (Ab.Ag-NPs) were synthesized for
      biomedical applications using a completely green biosynthetic method using
      Achillea biebersteinii flowers extract. The structure and properties of Ab.Ag-NPs
      were investigated using UV-visible spectroscopic techniques, transmission
      electron microscopy (TEM), zeta potential and energy dispersive X-ray
      spectrometers (EDS). The UV-visible spectroscopic analysis showed the absorbance
      peak at 460 nm, which indicates the synthesis of silver nanoparticles. The
      average particle diameter as determined by TEM was found to be 12+/-2 nm. The
      zeta potential analysis indicated that Ab.Ag-NPs have good stability EDX analysis
      also exhibits presentation of silver element. As angiogenesis is an important
      phenomenon and as growth factors imbalance in this process causes the
      acceleration of several diseases including cancer, the anti-angiogenic properties
      of Ab.Ag-NPs were evaluated using the rat aortic ring model. The results showed
      that Ab.Ag-NPs (200 MUg/mL) lead to a 50% reduction in the length and number of
      vessel-like structures. The synthesized silver nanoparticles from the Achillea
      biebersteinii flowers extract, which do not involve any harmful chemicals were
      well-dispersed and stabilized through this green method and showed potential
      therapeutic benefits against angiogenesis.

PMID- 24739927
TI  - Magnetically recoverable ruthenium catalysts in organic synthesis.
AB  - Magnetically recyclable catalysts with magnetic nanoparticles (MNPs) are becoming
      a major trend towards sustainable catalysts. In this area, recyclable supported
      ruthenium complexes and ruthenium nanoparticles occupy a key place and present
      great advantages compared to classic catalysts. In this micro-review, attention
      is focused on the fabrication of MNP-supported ruthenium catalysts and their
      catalytic applications in various organic syntheses. 

PMID- 24739928
TI  - Silymarin induces expression of pancreatic Nkx6.1 transcription factor and beta
      cells neogenesis in a pancreatectomy model.
AB  - A physio-pathological feature of diabetes mellitus is a significant reduction of
      beta-pancreatic cells. The growth, differentiation and function maintenance of
      these cells is directed by transcription factors. Nkx6.1 is a key transcription
      factor for the differentiation, neogenesis and maintenance of beta-pancreatic
      cells. We reported that silymarin restores normal morphology and endocrine
      function of damaged pancreatic tissue after alloxan-induced diabetes mellitus in
      rats. The aim of this study was to analyze the effect of silymarin on Nkx6.1
      transcription factor expression and its consequence in beta cells neogenesis.
      Sixty male Wistar rats were partially pancreatectomized and divided into twelve
      groups. Six groups were treated with silymarin (200 mg/Kg p.o) for periods of 3,
      7, 14, 21, 42 and 63 days. Additionally, an unpancreatectomized control group was
      used. Nkx6.1 and insulin gene expression were assessed by RT-PCR assay in total
      pancreatic RNA. beta-Cell neogenesis was determined by immunoperoxidase assay.
      Silymarin treated group showed an increase of Nkx6.1 and insulin genic
      expression. In this group, there was an increment of beta-cell neogenesis in
      comparison to pancreatectomized untreated group. Silymarin treatment produced a
      rise in serum insulin and serum glucose normalization. These results suggest that
      silymarin may improve the reduction of beta pancreatic cells observed in diabetes
      mellitus. 

PMID- 24739930
TI  - In vitro antioxidant activities, free radical scavenging capacity, and tyrosinase
      inhibitory of flavonoid compounds and ferulic acid from Spiranthes sinensis
      (Pers.) Ames.
AB  - In this study, ultrasound-assisted extraction (UAE) and other methods of
      extracting flavonoid compounds and ferulic acid (FA) from S. sinensis were
      investigated. Five different extraction methods, including water extraction (W),
      water extraction using UAE (W+U), 75% ethanol extraction (E), 75% ethanol
      extraction using UAE (E+U), and supercritical CO2 extraction (SFE) were applied
      in the extraction of bioactive compounds (flavonoids and ferulic acid) in order
      to compare their efficiency. The highest yield of flavonoids (4.28 mg/g) and
      ferulic acid (4.13 mg/g) content was detected in the E+U extract. Furthermore, S.
      sinensis extracts obtained by E+U show high antioxidant activity, and IC50 values
      of 0.47 mg/mL for DPPH radicals and 0.205 mg/mL for metal chelating activity. The
      total antioxidant assay shows superoxide radical scavenging capacity and in vitro
      mushroom tyrosinase inhibition in a dose-dependent manner, suggesting that E+U
      can be used for extraction of bioactive compounds from S. sinensis. 

PMID- 24739929
TI  - Cornu cervi pantotrichum supplementation improves exercise performance and
      protects against physical fatigue in mice.
AB  - Cornu cervi pantotrichum (CCP) is a well-known yang-invigorating agent used in
      traditional Chinese medicine that can nourish the blood, tonify qi, and
      invigorate bones and tendons with multifunctional bioactivities. However,
      evidence on the effects of CCP on exercise performance and physical fatigue is
      limited. We evaluated the potential beneficial effects of ethanolic extract from
      CCP on ergogenic and antifatigue functions following a physiological challenge.
      Male ICR mice from four groups (n=8 per group) were orally administered CCP for
      14 days at 0, 2054, and 4108 mg/kg/day, and were respectively designated as the
      vehicle, CCP-1X, and CCP-2X groups. The physical performance and antifatigue
      function were evaluated using forelimb grip strength and exhaustive swimming time
      as well as serum levels of lactate, ammonia, glucose, and creatine kinase after a
      15-min swimming exercise. The results indicated that CCP-1X supplementation
      significantly improved grip strength; reduced fatigue-associated biochemical
      indices, including lactate and ammonia levels; and ameliorated skeletal muscle
      injury induced by acute exercise challenge. A trend analysis revealed that CCP
      supplementation significantly increased grip strength and dose-dependently
      reduced serum alkaline phosphatase, uric acid, triacylglycerol, and glucose
      levels in healthy mice. Therefore, CCP is a potential agent with an antifatigue
      pharmacological effect.

PMID- 24739931
TI  - Molecular disorder in (-)-encecanescin.
AB  - (-)-Encecanescin (1) has been isolated from the leaves of Eupatorium
      aschembornianum. Two conformers are present in the crystal structure as a result
      of molecular disorder. The structure of 1 was established by 1H- and 13C-NMR
      spectroscopy in CDCl3 solution using 2D NMR techniques (gHSQC, gHMBC and NOESY).
      A Monte Carlo random search using molecular mechanics followed by the geometry
      optimization of each minimum energy structure using density functional theory
      (DFT) calculations at the B3LYP/6-31G* level and a Boltzmann analysis of the
      total energies generated accurate molecular models describing the conformational
      behavior of 1. The three most stable conformers 2-4 of compound 1 were
      reoptimized at the B3LYP/6-311++G(d,p) level of theory using CHCl3 as a solvent.
      Correlations between the experimental 1H- and 13C-NMR chemical shifts (deltaexp)
      have been found, and the GIAO/B3LYP/6-311++G(d,p) calculated magnetic isotropic
      shielding tensors (sigmacalc) for conformers 2 and 3, deltaexp=a+b sigmacalc, are
      reported. A good linear relationship between the experimental and calculated NMR
      data has been obtained for protons and carbon atoms.

PMID- 24739932
TI  - Sensory TRP channel interactions with endogenous lipids and their biological
      outcomes.
AB  - Lipids have long been studied as constituents of the cellular architecture and
      energy stores in the body. Evidence is now rapidly growing that particular lipid
      species are also important for molecular and cellular signaling. Here we review
      the current information on interactions between lipids and transient receptor
      potential (TRP) ion channels in nociceptive sensory afferents that mediate pain
      signaling. Sensory neuronal TRP channels play a crucial role in the detection of
      a variety of external and internal changes, particularly with damaging or pain
      eliciting potentials that include noxiously high or low temperatures, stretching,
      and harmful substances. In addition, recent findings suggest that TRPs also
      contribute to altering synaptic plasticity that deteriorates chronic pain states.
      In both of these processes, specific lipids are often generated and have been
      found to strongly modulate TRP activities, resulting primarily in pain
      exacerbation. This review summarizes three standpoints viewing those lipid
      functions for TRP modulations as second messengers, intercellular transmitters,
      or bilayer building blocks. Based on these hypotheses, we discuss perspectives
      that account for how the TRP-lipid interaction contributes to the peripheral pain
      mechanism. Still a number of blurred aspects remain to be examined, which will be
      answered by future efforts and may help to better control pain states. 

PMID- 24739933
TI  - Origin of subdiffusion of water molecules on cell membrane surfaces.
AB  - Water molecules play an important role in providing unique environments for
      biological reactions on cell membranes. It is widely believed that water
      molecules form bridges that connect lipid molecules and stabilize cell membranes.
      Using all-atom molecular dynamics simulations, we show that translational and
      rotational diffusion of water molecules on lipid membrane surfaces exhibit
      subdiffusion and aging. Moreover, we provide evidence that both divergent mean
      trapping time (continuous-time random walk) and long-correlated noise (fractional
      Brownian motion) contribute to this subdiffusion. These results suggest that
      subdiffusion on cell membranes causes the water retardation, an enhancement of
      cell membrane stability, and a higher reaction efficiency. 

PMID- 24739934
TI  - Dynamic localization of glucokinase and its regulatory protein in hypothalamic
      tanycytes.
AB  - Glucokinase (GK), the hexokinase involved in glucose sensing in pancreatic beta
      cells, is also expressed in hypothalamic tanycytes, which cover the ventricular
      walls of the basal hypothalamus and are implicated in an indirect control of
      neuronal activity by glucose. Previously, we demonstrated that GK was
      preferentially localized in tanycyte nuclei in euglycemic rats, which has been
      reported in hepatocytes and is suggestive of the presence of the GK regulatory
      protein, GKRP. In the present study, GK intracellular localization in
      hypothalamic and hepatic tissues of the same rats under several glycemic
      conditions was compared using confocal microscopy and Western blot analysis. In
      the hypothalamus, increased GK nuclear localization was observed in hyperglycemic
      conditions; however, it was primarily localized in the cytoplasm in hepatic
      tissue under the same conditions. Both GK and GKRP were next cloned from primary
      cultures of tanycytes. Expression of GK by Escherichia coli revealed a functional
      cooperative protein with a S0.5 of 10 mM. GKRP, expressed in Saccharomyces
      cerevisiae, inhibited GK activity in vitro with a Ki 0.2 uM. We also demonstrated
      increased nuclear reactivity of both GK and GKRP in response to high glucose
      concentrations in tanycyte cultures. These data were confirmed using Western blot
      analysis of nuclear extracts. Results indicate that GK undergoes short-term
      regulation by nuclear compartmentalization. Thus, in tanycytes, GK can act as a
      molecular switch to arrest cellular responses to increased glucose. 

PMID- 24739935
TI  - Prenatal smoking and genetic risk: examining the childhood origins of
      externalizing behavioral problems.
AB  - An ever-growing body of research has begun to focus closely on the role of
      prenatal smoke exposure in the development of conduct problems in children. To
      this point, there appears to be a correlation between prenatal nicotine exposure
      and behavioral problems. We build on this prior research by examining the
      coalescence of prenatal smoke exposure and genetic risk factors in the prediction
      of behavior problems. Specifically, the current study analyzed data from a
      nationally representative sample of twin pairs collected during early childhood.
      Our findings suggested that an interaction existed between prenatal smoke
      exposure and genetic risk factors which corresponded to increased risk of
      behavior problems. These findings provide evidence of a gene-environment
      interaction, in that prenatal smoke exposure conditioned the influence of genetic
      risk factors in the prediction of aggressive behavior. Interestingly, the
      association between genetic risk and prenatal smoking was sex-specific, and only
      reached statistical significance in females. Given the nature of our findings, it
      may shed light on why heterogeneity exists concerning the relationship between
      prenatal smoke exposure and externalizing behavioral problems in children. 

PMID- 24739936
TI  - The geography of chronic obstructive pulmonary disease: a population-based study
      of Norway.
AB  - Research on chronic obstructive pulmonary disease (COPD) that includes geographic
      information is important in order to improve care and appropriate allocation of
      resources to patients suffering from COPD. The purpose of this study is to
      investigate the geography of COPD and factors associated with the spatial
      patterns of COPD prevalence. Particular emphasis is put on the role of the local
      socioeconomic environment. Utilising information from the Norwegian Prescription
      Database on all lung medication prescribed in 2009 we identified 62,882 persons
      with COPD in the Norwegian population. Patterns of spatial clustering in the
      prevalence of COPD are clearly evident, even when age and gender are controlled
      for. Gender and age are strongly related to COPD risk. Socio-economic
      characteristics of the community such as education and unemployment are also
      significantly correlated with COPD risk. People living in rural parts of the
      country are generally associated with less risk than people in urban settings,
      and in particular people living in communities with high levels of farm and
      fisheries employment. 

PMID- 24739937
TI  - Impact of daily high-dose caffeine exposure on developing white matter of the
      immature ovine brain.
AB  - BACKGROUND: Caffeine is widely used to treat apnea of prematurity, but the
      standard dosing regimen is not always sufficient to prevent apnea. Before higher
      doses of caffeine can be used, their effects on the immature brain need to be
      carefully evaluated. Our aim was to determine the impact of daily high-dose
      caffeine administration on the developing white matter of the immature ovine
      brain. METHODS: High-dose caffeine (25 mg/kg caffeine base loading dose; 20 mg/kg
      daily maintenance dose; n = 9) or saline (n = 8) were administered to pregnant
      sheep from 0.7 to 0.8 of term, equivalent to approximately 27-34 wk in humans. At
      0.8 of term, the white and gray matter were assessed histologically and
      immunohistochemically. RESULTS: Daily caffeine administration led to peak
      caffeine concentration of 32 mg/l in fetal plasma at 1 h, followed by a gradual
      decline, with no effects on mean arterial pressure and heart rate. Initial
      caffeine exposure led to transient, mild alkalosis in the fetus but did not alter
      oxygenation. At necropsy, there was no effect of daily high-dose caffeine on
      brain weight, oligodendrocyte density, myelination, axonal integrity,
      microgliosis, astrogliosis, apoptosis, or neuronal density. CONCLUSION: Daily
      high-dose caffeine administration does not appear to adversely affect the
      developing white matter at the microstructural level.

PMID- 24739938
TI  - Study of the flying ability of Rhynchophorus ferrugineus (Coleoptera:
      Dryophthoridae) adults using a computer-monitored flight mill.
AB  - The red palm weevil, Rhynchophorus ferrugineus (Olivier) (Coleoptera:
      Dryophthoridae), native to tropical Asian regions, has become a serious threat to
      palm trees all over the world. Knowledge of its flight potential is vital to
      improving the preventive and curative measures currently used to manage this
      pest. As R. ferrugineus is a quarantine pest, it is difficult to study its flight
      potential in the field. A computer-monitored flight mill was adapted to analyse
      the flying ability of R. ferrugineus through the study of different flight
      parameters (number of flights, total distance flown, longest single flight,
      flight duration, and average and maximum speed) and the influence of the weevil's
      sex, age, and body size on these flight parameters. Despite significant
      differences in the adult body size (body weight and length) of males and females,
      the sex of R. ferrugineus adults did not have an influence on their flight
      potential. Neither adult body size nor age was found to affect the weevil's
      flying abilities, although there was a significantly higher percentage of
      individuals flying that were 8-23 days old than 1-7 days old. Compared to the
      longest single flight, 54% of the insects were classified as short-distance
      flyers (covering <100 m) and 36 and 10% were classified as medium- (100-5000 m)
      and long-distance (>5000 m), respectively. The results are compared with similar
      studies on different insect species under laboratory and field conditions.

PMID- 24739939
TI  - Factors associated with loneliness among mothers with 4-month-old or 18-month-old
      infants in an urban area in Japan.
AB  - OBJECTIVES: The factors associated with loneliness in adults and elderly people
      have been revealed in previous studies. However, much less is known about these
      factors for mothers with infants. This article investigates the individual and
      environmental factors associated with loneliness among mothers with 4-month-old
      or 18-month-old infants in an urban area in Japan. METHODS: This cross-sectional
      study was conducted using a self-reported questionnaire survey. Multiple linear
      regression analyses were undertaken with loneliness (UCLA Loneliness Scale
      Version 3) as the dependent variable; and demographics, individual factors
      (internal working model, child-care burden), and environmental factors (social
      network) as independent variables. RESULTS: The study population consisted of 125
      mothers with 4-month-old infants and 123 mothers with 18-month-old infants who
      visited a Ward B health center in city A in 2012. Mothers of the 4-month-old
      infants with higher loneliness scores were significantly more likely to have an
      ambivalent type (beta=.354, P<.001) or avoidant type (beta=.331, P<.001) of
      internal working model, greater child-care burden (beta=.180, P<.05), and a
      smaller social network of family (beta=-.144, P<.05) and child-rearing friends
      (beta=-.255, P<.01). Mothers of 18-month-old infants with higher loneliness
      scores were significantly more likely to have lower subjective health (beta=
      .191, P<.01), an ambivalent type (beta=.297, P<.001) or avoidant type (beta=.190,
      P<.05) of internal working model, greater child-care burden (beta=.283, P<.001),
      and a smaller social network of child-rearing friends (beta=-.213, P<.01).
      CONCLUSION: To prevent loneliness in mothers, it is important to build mothers'
      human relations through childcare, to enhance their ability to take advantage of
      childcare while receiving support, and to support community organizations for
      mothers with infants.

PMID- 24739940
TI  - The economic effects of smoking restriction within casual dining chain
      restaurants in Japan.
AB  - OBJECTIVES: One of the popular casual dining chain restaurants running 255
      outlets under the same brand name adopted the separation policy, mandating the
      differentiation of smoking and non-smoking zone in 2000. Following this, they
      started renovating the outlets' interiors because two thirds of them are dated.
      Going a step further, they have decided to implement stricter countermeasures
      against secondhand smoke. This includes the introduction of smoking prohibition
      outside the designated smoking room where foods are not served, and in some cases
      the separation of the smoking zone with glass walls and automatic doors. This
      study examined the economic effects of the smoking prohibition within a non
      designated smoking zone of casual dining chain restaurants in Japan. METHODS: We
      selected 59 outlets that prohibited smoking outside of the designated smoking
      room (prohibition group), and 17 outlets that separated the smoking zone with
      glass walls and automatic doors (separation group), all of which were renovated
      during the same time period, that is, February to December 2009. We compared the
      relative change in monthly sales of each restaurant two years before the
      renovation (24~13 months, 12~1 months) and one year after the renovation (1~12
      months) in order to exclude the effects of social economic regression and usual
      seasonal changes. Eighty-two outlets were not renovated during the observation
      period; hence, they were treated as the control group. For comparison purposes,
      the relative monthly sales of each outlet was collected and compared to the sales
      in January 2007, using a two-way repeated measures ANOVA and post-hoc analysis
      (Scheffe test) using SAS ver. 9.3. RESULTS: There was a significant difference
      among three groups across three different periods, P for group*time<0.0001.
      Relative sales of the prohibition group was significantly increased after the
      renovation (P<0.001); however, there was no significant increase in the relative
      sales of the separation group. CONCLUSION: Prohibition of smoking outside of the
      designated rooms in casual dining chain restaurants increased sales, while
      separation of the smoking zone did not.

PMID- 24739941
TI  - The 2011 measles outbreak in Tokyo. An analysis of surveillance data.
AB  - OBJECTIVES: The study was conducted with the intention of establishing a strategy
      to eliminate measles on the basis of an analysis of the epidemiological profile
      of measles cases reported in Tokyo during the year 2011. METHODS: We investigated
      measles cases reported to the Tokyo Metropolitan Government in 2011, recorded as
      part of the National Epidemiological Surveillance of Infectious Diseases. Factors
      analyzed included age, vaccination status for each patient, cases for which
      records were discarded after laboratory confirmation, genotype of the measles
      virus and relationships between dates of specimen collection and results of
      polymerase chain reaction (PCR) and IgM antibody tests. RESULTS: A total of 178
      measles cases were reported in Tokyo during 2011, and the majority of cases (128,
      71.9%) were reported during the peak period from epiweeks 13 to 24. The largest
      age group reported was one to four years of age (40, 22.5%) followed by groups of
      20-29 and 30-39 years of age (both 34, 19.1%). Most cases were sporadic, with
      only six outbreaks occurring. Even then, the numbers of cases for each outbreak
      was less than five. More than half of the patients in all age groups, except for
      the 1-4-year-old group, had not been vaccinated or did not have a record of
      vaccination. Genotypes D4 and D9 of measles virus were detected in most cases.
      However, genotype D5, which had been circulating in Japan before 2008, was not
      detected. CONCLUSION: Imported viruses were the cause of measles cases reported
      in Tokyo during 2011. The disease control was better than that in 2007 and 2008
      because of the swift and appropriate responses to the occurrences. It is also
      possible that there has been an increase in the proportion of people with
      immunity to measles. Increasing the rate of immunization, performing effective
      surveillance, and confirming suspicious measles cases by using molecular methods
      are important for achieving the elimination of measles.

PMID- 24739942
TI  - Sodium tanshinone IIA silate inhibits high glucose-induced vascular smooth muscle
      cell proliferation and migration through activation of AMP-activated protein
      kinase.
AB  - The proliferation of vascular smooth muscle cells may perform a crucial role in
      the pathogenesis of diabetic vascular disease. AMPK additionally exerts several
      salutary effects on vascular function and improves vascular abnormalities. The
      current study sought to determine whether sodium tanshinone IIA silate (STS) has
      an inhibitory effect on vascular smooth muscle cell (VSMC) proliferation and
      migration under high glucose conditions mimicking diabetes without dyslipidemia,
      and establish the underlying mechanism. In this study, STS promoted the
      phosphorylation of AMP-activated protein kinase (AMPK) at T172 in VSMCs. VSMC
      proliferation was enhanced under high glucose (25 mM glucose, HG) versus normal
      glucose conditions (5.5 mM glucose, NG), and this increase was inhibited
      significantly by STS treatment. We utilized western blotting analysis to evaluate
      the effects of STS on cell-cycle regulatory proteins and found that STS increased
      the expression of p53 and the Cdk inhibitor, p21, subsequent decreased the
      expression of cell cycle-associated protein, cyclin D1. We further observed that
      STS arrested cell cycle progression at the G0/G1 phase. Additionally, expression
      and enzymatic activity of MMP-2, translocation of NF-kappaB, as well as VSMC
      migration were suppressed in the presence of STS. Notably, Compound C (CC), a
      specific inhibitor of AMPK, as well as AMPK siRNA blocked STS-mediated inhibition
      of VSMC proliferation and migration. We further evaluated its potential for
      activating AMPK in aortas in animal models of type 2 diabetes and found that Oral
      administration of STS for 10 days resulted in activation of AMPK in aortas from
      ob/ob or db/db mice. In conclusion, STS inhibits high glucose-induced VSMC
      proliferation and migration, possibly through AMPK activation. The growth
      suppression effect may be attributable to activation of AMPK-p53-p21 signaling,
      and the inhibitory effect on migration to the AMPK/NF-kappaB signaling axis. 

PMID- 24739943
TI  - Key bifurcations of bursting polyrhythms in 3-cell central pattern generators.
AB  - We identify and describe the key qualitative rhythmic states in various 3-cell
      network motifs of a multifunctional central pattern generator (CPG). Such CPGs
      are neural microcircuits of cells whose synergetic interactions produce multiple
      states with distinct phase-locked patterns of bursting activity. To study
      biologically plausible CPG models, we develop a suite of computational tools that
      reduce the problem of stability and existence of rhythmic patterns in networks to
      the bifurcation analysis of fixed points and invariant curves of a Poincare
      return maps for phase lags between cells. We explore different functional
      possibilities for motifs involving symmetry breaking and heterogeneity. This is
      achieved by varying coupling properties of the synapses between the cells and
      studying the qualitative changes in the structure of the corresponding return
      maps. Our findings provide a systematic basis for understanding plausible
      biophysical mechanisms for the regulation of rhythmic patterns generated by
      various CPGs in the context of motor control such as gait-switching in
      locomotion. Our analysis does not require knowledge of the equations modeling the
      system and provides a powerful qualitative approach to studying detailed models
      of rhythmic behavior. Thus, our approach is applicable to a wide range of
      biological phenomena beyond motor control. 

PMID- 24739944
TI  - Assessment of postural balance among individuals with Parkinson disease with and
      without effects from dopaminergic medications.
AB  - OBJECTIVE: The objectives of the present study were to assess the effects of
      dopaminergic drugs on the postural balance of Parkinson disease (PD) patients and
      to ascertain whether their sway is greater along the mediolateral or the
      anteroposterior axis. DESIGN: Twenty-two patients awaiting operations for
      implantation of a deep brain stimulator at the neurology service of Hospital das
      Clinicas, University of Sao Paulo School of Medicine (HC-FMUSP), were assessed.
      All of them were assessed on the AccuSway portable force platform, through
      evaluation of the center of pressure. The patients stayed standing upright on
      both feet with the eyes open and closed for 60-sec periods. Center-of-pressure
      displacements along the mediolateral and anteroposterior axes and the
      displacement velocity and the elliptical area covered by 95% of the displacement
      were measured. Two assessments were made: without medication (at least 12 hrs
      after the last administration) and with the effects from levodopa. RESULTS: The
      elliptical displacement area was greater when the patients were under the effects
      of the medication (P < 0.05). The center-of-pressure displacements were greater
      along the anteroposterior axis than along the mediolateral axis. CONCLUSIONS:
      Levodopa increases the sway area of the Parkinson disease patients evaluated by
      static posturography.

PMID- 24739945
TI  - Outbreak of Clostridium difficile PCR ribotype 027--the recent experience of a
      regional hospital.
AB  - BACKGROUND: Clostridium difficile infection (CDI) is the leading cause of
      healthcare-associated diarrhea, and several outbreaks with increased severity and
      mortality have been reported. In this study we report a C. difficile PCR ribotype
      027 outbreak in Portugal, aiming to contribute to a better knowledge of the
      epidemiology of this agent in Europe. METHODS: Outbreak report with retrospective
      study of medical records and active surveillance data of all inpatients with the
      diagnosis of CDI, from 1st January to 31th December 2012, in a Portuguese
      hospital. C. difficile isolates were characterized regarding ribotype, toxin
      genes and moxifloxin resistance. Outbreak control measures were taken, concerning
      communication, education, reinforcement of infection control measures,
      optimization of diagnosis and treatment of CDI, and antibiotic stewardship.
      RESULTS: Fifty-three inpatients met the case definition of C. difficile
      associated infection: 55% males, median age was 78.0 years (interquartile range:
      71.0-86.0), 75% had co-morbidities, only 15% had a nonfatal condition, 68% had at
      least one criteria of severe disease at diagnosis, 89% received prior
      antibiotherapy, 79% of episodes were nosocomial. CDI rate peak was 13.89/10,000
      bed days. Crude mortality rate at 6 months was 64.2% while CDI attributable cause
      was 11.3%. Worse outcome was related to older age (P = 0.022), severity criteria
      at diagnosis (leukocytosis (P = 0.008) and renal failure), and presence of fatal
      underlying condition (P = 0.025). PCR ribotype 027 was identified in 16 of 22
      studied samples. CONCLUSIONS: This is the first report of a 027-CDI outbreak in
      Portugal. We emphasize the relevance of the measures taken to control the
      outbreak and highlight the importance of implementing a close and active
      surveillance of CDI.

PMID- 24739948
TI  - Evidence for the identification of Carabayo, the language of an uncontacted
      people of the Colombian Amazon, as belonging to the Tikuna-Yuri linguistic
      family.
AB  - This paper provides evidence for the identification of the language of the
      uncontacted indigenous group called Carabayo, who live in voluntary isolation in
      the Colombian Amazon region. The only linguistic data available from this group
      is a set of about 50 words, most of them without reliable translations, that were
      collected in 1969 during a brief encounter with one Carabayo family. We compare
      this material with various languages (once) spoken in the region, showing that
      four attested Carabayo forms (a first person singular prefix and words for
      'warm', 'father', and 'boy') display striking similarities with Yuri and at least
      13 Carabayo forms display clear correspondences with contemporary Tikuna. Tikuna
      and Yuri are the only two known members of the Tikuna-Yuri linguistic family.
      Yuri was documented in the 19th century but has been thought to have become
      extinct since. We conclude that the Carabayo--directly or indirectly--descend
      from the Yuri people whose language and customs were described by explorers in
      the 19th century, before they took up voluntary isolation, escaping atrocities
      during the rubber boom in the early 20th century.

PMID- 24739947
TI  - Dickkopf-related protein 1 inhibits the WNT signaling pathway and improves pig
      oocyte maturation.
AB  - The ability to mature oocytes in vitro provides a tool for creating embryos by
      parthenogenesis, fertilization, and cloning. Unfortunately the quality of oocytes
      matured in vitro falls behind that of in vivo matured oocytes. To address this
      difference, transcriptional profiling by deep sequencing was conducted on pig
      oocytes that were either matured in vitro or in vivo. Alignment of over 18
      million reads identified 1,316 transcripts that were differentially represented.
      One pathway that was overrepresented in the oocytes matured in vitro was for
      Wingless-type MMTV integration site (WNT) signaling. In an attempt to inhibit the
      WNT pathway, Dickkopf-related protein 1 was added to the in vitro maturation
      medium. Addition of Dickkopf-related protein 1 improved the percentage of oocytes
      that matured to the metaphase II stage, increased the number of nuclei in the
      resulting blastocyst stage embryos, and reduced the amount of disheveled segment
      polarity protein 1 protein in oocytes. It is concluded that transcriptional
      profiling is a powerful method for detecting differences between in vitro and in
      vivo matured oocytes, and that the WNT signaling pathway is important for proper
      oocyte maturation. 

PMID- 24739949
TI  - Molecular analysis and phenotypic study in 14 Chinese families with Bietti
      crystalline dystrophy.
AB  - PURPOSE: To investigate the clinical features and cytochrome P450 family 4
      subfamily V polypeptide 2 (CYP4V2) gene mutations in 14 Chinese families with
      Bietti crystalline dystrophy (BCD). METHODS: Seventeen patients from 14 unrelated
      Chinese families with BCD were recruited for complete clinical ophthalmic
      examination and genetic study. The 11 exons of CYP4V2 were amplified from genomic
      DNA of all patients and their family members by polymerase chain reaction (PCR)
      and then sequenced. Exons of TIMP3 were also sequenced in BCD patient associated
      with choroidal neovascularization (CNV). One hundred and seventy unrelated
      healthy Chinese subjects were screened for mutations in CYP4V2. RESULTS: All 17
      patients with BCD had mutations in CYP4V2; one of these mutations was novel
      (c.219T>A, p.F73L) and four other mutations had been reported. The p.F73L
      mutation was a commonly detected mutation in our study (seven out of 34 alleles),
      either in the homozygous state or in the heterozygous state. Among the patients,
      considerable phenotypic variability was detected, both within and between
      families. Screening of TIMP3 did not find any mutation in the BCD patient
      associated with CNV. CONCLUSION: The novel CYP4V2 c.219T>A (p.F73L) mutation may
      be another recurrent mutation in Chinese patients with BCD. Our study expands the
      mutation spectrum of CYP4V2 and characterizes novel genotype-phenotype
      associations in Chinese patients with BCD.

PMID- 24739951
TI  - HIV-1 Tat-mediated apoptosis in human blood-retinal barrier-associated cells.
AB  - HIV-1-associated ocular complications, such as microvasculopathies, can lead to
      the loss of vision in HIV-1-infected patients. Even in patients under highly
      active antiretroviral therapy, ocular lesions are unavoidable. Ocular
      complications have been demonstrated to be closely related to the breakdown of
      the blood-retinal-barrier (BRB); however, the underlying mechanism is not clear.
      The data from this study indicated that the HIV-1 Tat protein induced the
      apoptosis of human retinal microvascular endothelial cells (HRMECs) and retinal
      pigmen epithelium (RPE) cells, which compose the inner BRB and the outer BRB,
      respectively. In addition, this study found that the activation of N-methyl-D
      aspartate receptors (NMDARs) was involved in the apoptosis of RPE cells, but it
      caused no changes in HRMECs. Furthermore, both cell types exhibited enhanced
      expression of Bak, Bax and Cytochrome c. The inhibition of Tat activity protected
      against the apoptosis induced by NMDAR activation and prevented the dysregulation
      of Bak, Bax and Cytochrome c, revealing an important role for the mitochondrial
      pathway in HIV-1 Tat-induced apoptosis. Together, these findings suggest a
      possible mechanism and may identify a potential therapeutic strategy for HIV-1
      associated ocular complications. 

PMID- 24739952
TI  - Potential use of a megamolecular polysaccharide sacran as a hydrogel-based
      sustained release system.
AB  - A megamolecular polysaccharide sacran was newly extracted from cyanobacterium
      Aphanothece sacrum. Sacran has many preferable properties for transdermal
      application, e.g. a safe biomaterial, a high moisturizing effect, a formation of
      film and hydrogel. Additionally, it was recently discovered that sacran has an
      anti-inflammatory effect for atopic dermatitis model mice. In this study, in
      order to evaluate the feasibility of sacran-hydrogel as a novel sustained release
      system, we prepared a sacran-hydrogel containing 4-biphenyl acetic acid (BPAA, an
      acidic drug), prednisolone (PD, a neutral drug) or chlorpheniramine maleate (CPM,
      a basic drug), and performed the in vitro release studies. The sacran-hydrogel
      containing BPAA, PD or CPM provided a sustained release profile in accordance
      with a quasi-Fickian diffusion model. Furthermore, the release rate of drugs from
      sacran-hydrogels can be controlled by adjusting the concentration of aluminum
      chloride as a cross linker. These results suggest the potential use of sacran
      hydrogel as a sustained release system for drugs. 

PMID- 24739950
TI  - Regulatory B cells inhibit cytotoxic T lymphocyte (CTL) activity and elimination
      of infected CD4 T cells after in vitro reactivation of HIV latent reservoirs.
AB  - During HIV infection, IL-10/IL-10 receptor and programmed death-1 (PD
      1)/programmed death-1-ligand (PD-L1) interactions have been implicated in the
      impairment of cytotoxic T lymphocyte (CTL) activity. Despite antiretroviral
      therapy (ART), attenuated anti-HIV CTL functions present a major hurdle towards
      curative measures requiring viral eradication. Therefore, deeper understanding of
      the mechanisms underlying impaired CTL is crucial before HIV viral eradication is
      viable. The generation of robust CTL activity necessitates interactions between
      antigen-presenting cells (APC), CD4+ and CD8+ T cells. We have shown that in
      vitro, IL-10hiPD-L1hi regulatory B cells (Bregs) directly attenuate HIV-specific
      CD8+-mediated CTL activity. Bregs also modulate APC and CD4+ T cell function;
      herein we characterize the Breg compartment in uninfected (HIVNEG), HIV-infected
      "elite controllers" (HIVEC), ART-treated (HIVART), and viremic (HIVvir),
      subjects, and in vitro, assess the impact of Bregs on anti-HIV CTL generation and
      activity after reactivation of HIV latent reservoirs using suberoylanilide
      hydroxamic acid (SAHA). We find that Bregs from HIVEC and HIVART subjects exhibit
      comparable IL-10 expression levels significantly higher than HIVNEG subjects, but
      significantly lower than HIVVIR subjects. Bregs from HIVEC and HIVART subjects
      exhibit comparable PD-L1 expression, significantly higher than in HIVVIR and
      HIVNEG subjects. SAHA-treated Breg-depleted PBMC from HIVEC and HIVART subjects,
      displayed enhanced CD4+ T-cell proliferation, significant upregulation of antigen
      presentation molecules, increased frequency of CD107a+ and HIV-specific CD8+ T
      cells, associated with efficient elimination of infected CD4+ T cells, and
      reduction in integrated viral DNA. Finally, IL-10-R and PD-1 antibody blockade
      partially reversed Breg-mediated inhibition of CD4+ T-cell proliferation. Our
      data suggest that, possibly, via an IL-10 and PD-L1 synergistic mechanism; Bregs
      likely inhibit APC function and CD4+ T-cell proliferation, leading to anti-HIV
      CTL attenuation, hindering viral eradication. 

PMID- 24739953
TI  - Role of genetic variants of autophagy genes in susceptibility for non-medullary
      thyroid cancer and patients outcome.
AB  - Autophagy is a central process in regulation of cell survival, cell death and
      proliferation and plays an important role in carcinogenesis, including thyroid
      carcinoma. Genetic variation in autophagy components has been demonstrated to
      influence the capacity to execute autophagy and is associated with disease
      susceptibility, progression and outcome. In the present study, we assessed
      whether genetic variation in autophagy genes contributes to susceptibility to
      develop thyroid carcinoma, disease progression and/or patient outcome. The
      results indicate that patients carrying the ATG5 single nucleotide polymorphisms
      rs2245214 have a higher probability to develop thyroid carcinoma (OR 1.85 (95% CI
      1.04-3.23), P = 0.042). In contrast, no significant differences could be observed
      for the other genetic variants studied in terms of thyroid carcinoma
      susceptibility. Furthermore, none of the selected genetic variants were
      associated with clinical parameters of disease progression and outcome. In
      conclusion, genetic variation in ATG5, a central player in the autophagy process,
      is found to be associated with increased susceptibility for thyroid carcinoma,
      indicating a role for autophagy in thyroid carcinogenesis. 

PMID- 24739955
TI  - The implementation of a dual dispatch system in out-of-hospital cardiac arrest is
      associated with improved short and long term survival.
AB  - AIMS: To determine the impact of a dual dispatch system, using fire fighters as
      first responders, in out-of-hospital cardiac arrest (OHCA) on short (30 days) and
      long term (three years) survival, and, to investigate the potential differences
      regarding in-hospital factors and interventions between the patient groups, such
      as the use of therapeutic hypothermia and cardiac catheterization. METHODS AND
      RESULTS: OHCAs from 2004 (historical controls) and 2006-2009 (intervention
      period) were included. During the intervention period, fire fighters equipped
      with automated external defibrillators (AEDs) were dispatched in suspected OHCA.
      Logistic regression analyses of outcome data included: the intervention with dual
      dispatch, sex, age, location, aetiology, witnessed status, bystander
      cardiopulmonary resuscitation, first rhythm and therapeutic hypothermia. In
      total, 2581 OHCAs were included (historical controls n=620, intervention period
      n=1961). Fire fighters initiated cardiopulmonary resuscitation and connected an
      AED before emergency medical services' arrival in 41% of the cases. The median
      time from dispatch to arrival of first responder or emergency medical services
      shortened from 7.7 in the control period to 6.7 min in the intervention period
      (p<0.001). The 30-day survival improved from 3.9% to 7.6% (p=0.001), adjusted
      odds ratio 2.8 (confidence interval 1.6-4.9). Survival to three years increased
      from 2.4% to 6.5% (p<0.001), adjusted odds ratio 3.8 (confidence interval 1.9
      7.6). In the logistic regression analysis including in-hospital factors we found
      no outcome benefit of therapeutic hypothermia. CONCLUSIONS: The implementation of
      a dual dispatch system using fire fighters in OHCA was associated with increased
      30-day and three-year survival. No major differences in the in-hospital treatment
      were seen between the studied patient groups.

PMID- 24739956
TI  - Dairy sheep production research at the University of Wisconsin-Madison, USA - a
      review.
AB  - Commercial milking of sheep is a new agricultural industry in the United States
      starting approximately 30 yr ago. The industry is still small, but it is growing.
      The majority of the sheep milk is used in the production of specialty cheeses.
      The United States is the major importer of sheep milk cheeses with 50 to 60% of
      annual world exports coming to the United States during the past 20 yr.
      Therefore, there is considerable growth potential for the industry in the United
      States. The only dairy sheep research flock in North America is located at the
      Spooner Agricultural Research Station of the University of Wisconsin-Madison. The
      research program started in 1993 and has been multifaceted; dealing with several
      areas important to commercial dairy sheep farmers. The East Friesian and Lacaune
      dairy breeds were compared and introduced to the industry through the research
      program. Both dairy breeds produced significantly more milk than traditional meat
      wool breeds found in the U.S., but the two breeds differed in their production
      traits. East Friesian-cross ewes produced more lambs and slightly more milk than
      Lacaune-cross ewes whereas Lacaune-cross ewes produced milk with a higher
      percentage of fat and protein than East Friesian-cross ewes. Lactation physiology
      studies have shown that ewes with active corpora lutea have increased milk
      yields, oxytocin release during milking is required to obtain normal fat
      percentages in the milk, large udder cisterns of dairy ewes can allow for
      increased milking intervals, and short daylengths during late pregnancy results
      in increased milk yield. In the nutrition area, legume-grass pastures and forages
      with a higher percentage of legume will result in increased milk production.
      Grazing ewes respond to additional supplementation with increased milk yield, but
      it is important to match the supplement to the quality of the grazing. Ewes on
      high quality legume-grass pastures that are high in rumen degradable protein
      respond with increased milk production to supplements high in energy and/or high
      in rumen undegraded protein. 

PMID- 24739954
TI  - Parallel mRNA and microRNA profiling of HEV71-infected human neuroblastoma cells
      reveal the up-regulation of miR-1246 in association with DLG3 repression.
AB  - Human enterovirus 71 (HEV71) has emerged as the leading cause of viral
      encephalitis in children in most Asian countries. The roles of host miRNAs in the
      neurological pathogenesis of HEV71 infection remain unknown. In the present
      study, comprehensive miRNA expression profiling in HEV71-infected human
      neuroblastoma SH-SY5Y cells was performed using the Affymetrix Gene Chip
      microarray assay and was validated using real-time RT-PCR. Among the 69
      differentially expressed miRNAs, miR-1246 was specifically induced by HEV71
      infection in human neuroblastoma cells, but inhibition of miR-1246 failed to
      affect HEV71 replication. Parallel mRNA and microRNA profiling based on the 35 K
      Human Genome Array identified 182 differentially regulated genes. Target
      prediction of miR-1246 and network modeling revealed 14 potential target genes
      involved in cell death and cell signaling. Finally, a combined analysis of the
      results from mRNA profiling and miR-1246 target predication led to the
      identification of disc-large homolog 3 (DLG3), which is associated with
      neurological disorders, for further validation. Sequence alignment and luciferase
      reporter assay showed that miR-1246 directly bound with the 3'-UTR of DLG3 gene.
      Down-regulation of miR-1246 induced significant changes in DLG3 expression levels
      in HEV71-infected SHSY5Y cells. Together, these results suggested that miR-1246
      might play a role in neurological pathogenesis of HEV71 by regulating DLG3 gene
      in infected cells. These findings provide new information on the miRNA and mRNA
      profiles of HEV71-infected neuroblastoma cells. The biological significance of
      miR-1246 and DLG3 during the course of HEV71 infection deserves further
      investigation. 

PMID- 24739957
TI  - Chemical modulation of the biological activity of reutericyclin: a membrane
      active antibiotic from Lactobacillus reuteri.
AB  - Whilst the development of membrane-active antibiotics is now an attractive
      therapeutic concept, progress in this area is disadvantaged by poor knowledge of
      the structure-activity relationship (SAR) required for optimizing molecules to
      selectively target bacteria. This prompted us to explore the SAR of the
      Lactobacillus reuteri membrane-active antibiotic reutericyclin, modifying three
      key positions about its tetramic acid core. The SAR revealed that lipophilic
      analogs were generally more active against Gram-positive pathogens, but
      introduction of polar and charged substituents diminished their activity. This
      was confirmed by cytometric assays showing that inactive compounds failed to
      dissipate the membrane potential. Radiolabeled substrate assays indicated that
      dissipation of the membrane potential by active reutericyclins correlated with
      inhibition of macromolecular synthesis in cells. However, compounds with good
      antibacterial activities also showed cytotoxicity against Vero cells and
      hemolytic activity. Although this study highlights the challenge of optimizing
      membrane-active antibiotics, it shows that by increasing antibacterial potency
      the selectivity index could be widened, allowing use of lower non-cytotoxic
      doses. 

PMID- 24739958
TI  - Personalised anticoagulation approach to improve the prevention and treatment of
      thrombosis.

PMID- 24739959
TI  - Patterns of trematode infections of Opisthorchis viverrini (Opisthorchiidae) and
      Haplorchis taichui (Heterophyidae) in human populations from two villages in
      Savannakhet Province, Lao PDR.
AB  - The liver fluke, Opisthorchis viverrini, and the minute intestinal fluke,
      Haplorchis taichui, are prevalent in many Asian countries. This study analysed
      the patterns of infections of O. viverrini and H. taichui in Lahanam and
      Thakhamlien villages (Savannakhet Province, Lao PDR), in two cross-sectional
      investigations. Out of a total of 207 human participants, post-anthelmintic
      treatment positivity rates for expelled worms were 170 (82.1%) for H. taichui and
      65 (31.4%) for O. viverrini. Both these species co-exist in the study villages.
      When each parasite was analysed separately, H. taichui infections reached a
      plateau among people aged >20 years. Opisthorchis viverrini infection rates were
      highest in the age group 21-30 years, with decreasing infection rates after the
      age of 30. Our findings indicated that fish-borne trematode infections were more
      prevalent among adults. Fish, common intermediate hosts, were acquired in the
      study area for analysis. The examination of 35 species of fish as intermediate
      hosts found O. viverrini metacercariae in only six species, and these were found
      mostly during the month of November. Many farmers who live on the rice fields
      obtain their food from their immediate environment, including these intermediate
      host fish, potentially putting them at greater risk of O. viverrini infection. By
      contrast, H. taichui metacercariae were found in three species of fish obtained
      from the market, meaning that anyone could consume them and become infected. If
      people who work in rice fields limit the species of fish they consume, or avoid
      consuming raw fish during the month of November, they may reduce their risk of O.
      viverrini infection. 

PMID- 24739960
TI  - Sea-level and deep-sea-temperature variability over the past 5.3 million years.
AB  - Ice volume (and hence sea level) and deep-sea temperature are key measures of
      global climate change. Sea level has been documented using several independent
      methods over the past 0.5 million years (Myr). Older periods, however, lack such
      independent validation; all existing records are related to deep-sea oxygen
      isotope (delta(18)O) data that are influenced by processes unrelated to sea
      level. For deep-sea temperature, only one continuous high-resolution (Mg/Ca
      based) record exists, with related sea-level estimates, spanning the past 1.5
      Myr. Here we present a novel sea-level reconstruction, with associated estimates
      of deep-sea temperature, which independently validates the previous 0-1.5 Myr
      reconstruction and extends it back to 5.3 Myr ago. We find that deep-sea
      temperature and sea level generally decreased through time, but distinctly out of
      synchrony, which is remarkable given the importance of ice-albedo feedbacks on
      the radiative forcing of climate. In particular, we observe a large temporal
      offset during the onset of Plio-Pleistocene ice ages, between a marked cooling
      step at 2.73 Myr ago and the first major glaciation at 2.15 Myr ago. Last, we
      tentatively infer that ice sheets may have grown largest during glacials with
      more modest reductions in deep-sea temperature. 

PMID- 24739961
TI  - Caspase-11 activation requires lysis of pathogen-containing vacuoles by IFN
      induced GTPases.
AB  - Lipopolysaccharide from Gram-negative bacteria is sensed in the host cell
      cytoplasm by a non-canonical inflammasome pathway that ultimately results in
      caspase-11 activation and cell death. In mouse macrophages, activation of this
      pathway requires the production of type-I interferons, indicating that interferon
      induced genes have a critical role in initiating this pathway. Here we report
      that a cluster of small interferon-inducible GTPases, the so-called guanylate
      binding proteins, is required for the full activity of the non-canonical caspase
      11 inflammasome during infections with vacuolar Gram-negative bacteria. We show
      that guanylate-binding proteins are recruited to intracellular bacterial
      pathogens and are necessary to induce the lysis of the pathogen-containing
      vacuole. Lysis of the vacuole releases bacteria into the cytosol, thus allowing
      the detection of their lipopolysaccharide by a yet unknown lipopolysaccharide
      sensor. Moreover, recognition of the lysed vacuole by the danger sensor galectin
      8 initiates the uptake of bacteria into autophagosomes, which results in a
      reduction of caspase-11 activation. These results indicate that host-mediated
      lysis of pathogen-containing vacuoles is an essential immune function and is
      necessary for efficient recognition of pathogens by inflammasome complexes in the
      cytosol. 

PMID- 24739962
TI  - NRROS negatively regulates reactive oxygen species during host defence and
      autoimmunity.
AB  - Reactive oxygen species (ROS) produced by phagocytes are essential for host
      defence against bacterial and fungal infections. Individuals with defective ROS
      production machinery develop chronic granulomatous disease. Conversely, excessive
      ROS can cause collateral tissue damage during inflammatory processes and
      therefore needs to be tightly regulated. Here we describe a protein, we termed
      negative regulator of ROS (NRROS), which limits ROS generation by phagocytes
      during inflammatory responses. NRROS expression in phagocytes can be repressed by
      inflammatory signals. NRROS-deficient phagocytes produce increased ROS upon
      inflammatory challenges, and mice lacking NRROS in their phagocytes show enhanced
      bactericidal activity against Escherichia coli and Listeria monocytogenes.
      Conversely, these mice develop severe experimental autoimmune encephalomyelitis
      owing to oxidative tissue damage in the central nervous system. Mechanistically,
      NRROS is localized to the endoplasmic reticulum, where it directly interacts with
      nascent NOX2 (also known as gp91(phox) and encoded by Cybb) monomer, one of the
      membrane-bound subunits of the NADPH oxidase complex, and facilitates the
      degradation of NOX2 through the endoplasmic-reticulum-associated degradation
      pathway. Thus, NRROS provides a hitherto undefined mechanism for regulating ROS
      production--one that enables phagocytes to produce higher amounts of ROS, if
      required to control invading pathogens, while minimizing unwanted collateral
      tissue damage.

PMID- 24739963
TI  - Juno is the egg Izumo receptor and is essential for mammalian fertilization.
AB  - Fertilization occurs when sperm and egg recognize each other and fuse to form a
      new, genetically distinct organism. The molecular basis of sperm-egg recognition
      is unknown, but is likely to require interactions between receptor proteins
      displayed on their surface. Izumo1 is an essential sperm cell-surface protein,
      but its receptor on the egg has not been described. Here we identify folate
      receptor 4 (Folr4) as the receptor for Izumo1 on the mouse egg, and propose to
      rename it Juno. We show that the Izumo1-Juno interaction is conserved within
      several mammalian species, including humans. Female mice lacking Juno are
      infertile and Juno-deficient eggs do not fuse with normal sperm. Rapid shedding
      of Juno from the oolemma after fertilization suggests a mechanism for the
      membrane block to polyspermy, ensuring eggs normally fuse with just a single
      sperm. Our discovery of an essential receptor pair at the nexus of conception
      provides opportunities for the rational development of new fertility treatments
      and contraceptives. 

PMID- 24739964
TI  - Climate science: Sea levels from ancient seashells.

PMID- 24739965
TI  - Reconstructing lineage hierarchies of the distal lung epithelium using single
      cell RNA-seq.
AB  - The mammalian lung is a highly branched network in which the distal regions of
      the bronchial tree transform during development into a densely packed honeycomb
      of alveolar air sacs that mediate gas exchange. Although this transformation has
      been studied by marker expression analysis and fate-mapping, the mechanisms that
      control the progression of lung progenitors along distinct lineages into mature
      alveolar cell types are still incompletely known, in part because of the limited
      number of lineage markers and the effects of ensemble averaging in conventional
      transcriptome analysis experiments on cell populations. Here we show that single
      cell transcriptome analysis circumvents these problems and enables direct
      measurement of the various cell types and hierarchies in the developing lung. We
      used microfluidic single-cell RNA sequencing (RNA-seq) on 198 individual cells at
      four different stages encompassing alveolar differentiation to measure the
      transcriptional states which define the developmental and cellular hierarchy of
      the distal mouse lung epithelium. We empirically classified cells into distinct
      groups by using an unbiased genome-wide approach that did not require a priori
      knowledge of the underlying cell types or the previous purification of cell
      populations. The results confirmed the basic outlines of the classical model of
      epithelial cell-type diversity in the distal lung and led to the discovery of
      many previously unknown cell-type markers, including transcriptional regulators
      that discriminate between the different populations. We reconstructed the
      molecular steps during maturation of bipotential progenitors along both alveolar
      lineages and elucidated the full life cycle of the alveolar type 2 cell lineage.
      This single-cell genomics approach is applicable to any developing or mature
      tissue to robustly delineate molecularly distinct cell types, define progenitors
      and lineage hierarchies, and identify lineage-specific regulatory factors. 

PMID- 24739966
TI  - Coordination of entorhinal-hippocampal ensemble activity during associative
      learning.
AB  - Accumulating evidence points to cortical oscillations as a mechanism for
      mediating interactions among functionally specialized neurons in distributed
      brain circuits. A brain function that may use such interactions is declarative
      memory--that is, memory that can be consciously recalled, such as episodes and
      facts. Declarative memory is enabled by circuits in the entorhinal cortex that
      interface the hippocampus with the neocortex. During encoding and retrieval of
      declarative memories, entorhinal and hippocampal circuits are thought to interact
      via theta and gamma oscillations, which in awake rodents predominate frequency
      spectra in both regions. In favour of this idea, theta-gamma coupling has been
      observed between entorhinal cortex and hippocampus under steady-state conditions
      in well-trained rats; however, the relationship between interregional coupling
      and memory formation remains poorly understood. Here we show, by multisite
      recording at successive stages of associative learning, that the coherence of
      firing patterns in directly connected entorhinal-hippocampus circuits evolves as
      rats learn to use an odour cue to guide navigational behaviour, and that such
      coherence is invariably linked to the development of ensemble representations for
      unique trial outcomes in each area. Entorhinal-hippocampal coupling was observed
      specifically in the 20-40-hertz frequency band and specifically between the
      distal part of hippocampal area CA1 and the lateral part of entorhinal cortex,
      the subfields that receive the predominant olfactory input to the hippocampal
      region. Collectively, the results identify 20-40-hertz oscillations as a
      mechanism for synchronizing evolving representations in dispersed neural circuits
      during encoding and retrieval of olfactory-spatial associative memory.

PMID- 24739967
TI  - Listeria monocytogenes exploits efferocytosis to promote cell-to-cell spread.
AB  - Efferocytosis, the process by which dying or dead cells are removed by
      phagocytosis, has an important role in development, tissue homeostasis and innate
      immunity. Efferocytosis is mediated, in part, by receptors that bind to exofacial
      phosphatidylserine (PS) on cells or cellular debris after loss of plasma membrane
      asymmetry. Here we show that a bacterial pathogen, Listeria monocytogenes, can
      exploit efferocytosis to promote cell-to-cell spread during infection. These
      bacteria can escape the phagosome in host cells by using the pore-forming toxin
      listeriolysin O (LLO) and two phospholipase C enzymes. Expression of the cell
      surface protein ActA allows L. monocytogenes to activate host actin regulatory
      factors and undergo actin-based motility in the cytosol, eventually leading to
      formation of actin-rich protrusions at the cell surface. Here we show that
      protrusion formation is associated with plasma membrane damage due to LLO's pore
      forming activity. LLO also promotes the release of bacteria-containing
      protrusions from the host cell, generating membrane-derived vesicles with
      exofacial PS. The PS-binding receptor TIM-4 (encoded by the Timd4 gene)
      contributes to efficient cell-to-cell spread by L. monocytogenes in macrophages
      in vitro and growth of these bacteria is impaired in Timd4(-/-) mice. Thus, L.
      monocytogenes promotes its dissemination in a host by exploiting efferocytosis.
      Our results indicate that PS-targeted therapeutics may be useful in the fight
      against infections by L. monocytogenes and other bacteria that use similar
      strategies of cell-to-cell spread during infection. 

PMID- 24739968
TI  - Structural basis of Sec-independent membrane protein insertion by YidC.
AB  - Newly synthesized membrane proteins must be accurately inserted into the
      membrane, folded and assembled for proper functioning. The protein YidC inserts
      its substrates into the membrane, thereby facilitating membrane protein assembly
      in bacteria; the homologous proteins Oxa1 and Alb3 have the same function in
      mitochondria and chloroplasts, respectively. In the bacterial cytoplasmic
      membrane, YidC functions as an independent insertase and a membrane chaperone in
      cooperation with the translocon SecYEG. Here we present the crystal structure of
      YidC from Bacillus halodurans, at 2.4 A resolution. The structure reveals a novel
      fold, in which five conserved transmembrane helices form a positively charged
      hydrophilic groove that is open towards both the lipid bilayer and the cytoplasm
      but closed on the extracellular side. Structure-based in vivo analyses reveal
      that a conserved arginine residue in the groove is important for the insertion of
      membrane proteins by YidC. We propose an insertion mechanism for single-spanning
      membrane proteins, in which the hydrophilic environment generated by the groove
      recruits the extracellular regions of substrates into the low-dielectric
      environment of the membrane. 

PMID- 24739969
TI  - Dynamics and associations of microbial community types across the human body.
AB  - A primary goal of the Human Microbiome Project (HMP) was to provide a reference
      collection of 16S ribosomal RNA gene sequences collected from sites across the
      human body that would allow microbiologists to better associate changes in the
      microbiome with changes in health. The HMP Consortium has reported the structure
      and function of the human microbiome in 300 healthy adults at 18 body sites from
      a single time point. Using additional data collected over the course of 12-18
      months, we used Dirichlet multinomial mixture models to partition the data into
      community types for each body site and made three important observations. First,
      there were strong associations between whether individuals had been breastfed as
      an infant, their gender, and their level of education with their community types
      at several body sites. Second, although the specific taxonomic compositions of
      the oral and gut microbiomes were different, the community types observed at
      these sites were predictive of each other. Finally, over the course of the
      sampling period, the community types from sites within the oral cavity were the
      least stable, whereas those in the vagina and gut were the most stable. Our
      results demonstrate that even with the considerable intra- and interpersonal
      variation in the human microbiome, this variation can be partitioned into
      community types that are predictive of each other and are probably the result of
      life-history characteristics. Understanding the diversity of community types and
      the mechanisms that result in an individual having a particular type or changing
      types, will allow us to use their community types to assess disease risk and to
      personalize therapies. 

PMID- 24739970
TI  - Reproductive biology: Sperm protein finds its mate.

PMID- 24739971
TI  - Predicting biodiversity change and averting collapse in agricultural landscapes.
AB  - The equilibrium theory of island biogeography is the basis for estimating
      extinction rates and a pillar of conservation science. The default strategy for
      conserving biodiversity is the designation of nature reserves, treated as islands
      in an inhospitable sea of human activity. Despite the profound influence of
      islands on conservation theory and practice, their mainland analogues, forest
      fragments in human-dominated landscapes, consistently defy expected biodiversity
      patterns based on island biogeography theory. Countryside biogeography is an
      alternative framework, which recognizes that the fate of the world's wildlife
      will be decided largely by the hospitality of agricultural or countryside
      ecosystems. Here we directly test these biogeographic theories by comparing a
      Neotropical countryside ecosystem with a nearby island ecosystem, and show that
      each supports similar bat biodiversity in fundamentally different ways. The
      island ecosystem conforms to island biogeographic predictions of bat species
      loss, in which the water matrix is not habitat. In contrast, the countryside
      ecosystem has high species richness and evenness across forest reserves and
      smaller forest fragments. Relative to forest reserves and fragments, deforested
      countryside habitat supports a less species-rich, yet equally even, bat
      assemblage. Moreover, the bat assemblage associated with deforested habitat is
      compositionally novel because of predictable changes in abundances by many
      species using human-made habitat. Finally, we perform a global meta-analysis of
      bat biogeographic studies, spanning more than 700 species. It generalizes our
      findings, showing that separate biogeographic theories for countryside and island
      ecosystems are necessary. A theory of countryside biogeography is essential to
      conservation strategy in the agricultural ecosystems that comprise roughly half
      of the global land surface and are likely to increase even further. 

PMID- 24739972
TI  - Focused specificity of intestinal TH17 cells towards commensal bacterial
      antigens.
AB  - T-helper-17 (TH17) cells have critical roles in mucosal defence and in autoimmune
      disease pathogenesis. They are most abundant in the small intestine lamina
      propria, where their presence requires colonization of mice with microbiota.
      Segmented filamentous bacteria (SFB) are sufficient to induce TH17 cells and to
      promote TH17-dependent autoimmune disease in animal models. However, the
      specificity of TH17 cells, the mechanism of their induction by distinct bacteria,
      and the means by which they foster tissue-specific inflammation remain unknown.
      Here we show that the T-cell antigen receptor (TCR) repertoire of intestinal TH17
      cells in SFB-colonized mice has minimal overlap with that of other intestinal
      CD4(+) T cells and that most TH17 cells, but not other T cells, recognize
      antigens encoded by SFB. T cells with antigen receptors specific for SFB-encoded
      peptides differentiated into RORgammat-expressing TH17 cells, even if SFB
      colonized mice also harboured a strong TH1 cell inducer, Listeria monocytogenes,
      in their intestine. The match of T-cell effector function with antigen
      specificity is thus determined by the type of bacteria that produce the antigen.
      These findings have significant implications for understanding how commensal
      microbiota contribute to organ-specific autoimmunity and for developing novel
      mucosal vaccines. 

PMID- 24739973
TI  - Oncogene-like induction of cellular invasion from centrosome amplification.
AB  - Centrosome amplification has long been recognized as a feature of human tumours;
      however, its role in tumorigenesis remains unclear. Centrosome amplification is
      poorly tolerated by non-transformed cells and, in the absence of selection, extra
      centrosomes are spontaneously lost. Thus, the high frequency of centrosome
      amplification, particularly in more aggressive tumours, raises the possibility
      that extra centrosomes could, in some contexts, confer advantageous
      characteristics that promote tumour progression. Using a three-dimensional model
      system and other approaches to culture human mammary epithelial cells, we find
      that centrosome amplification triggers cell invasion. This invasive behaviour is
      similar to that induced by overexpression of the breast cancer oncogene ERBB2
      (ref. 4) and indeed enhances invasiveness triggered by ERBB2. Our data indicate
      that, through increased centrosomal microtubule nucleation, centrosome
      amplification increases Rac1 activity, which disrupts normal cell-cell adhesion
      and promotes invasion. These findings demonstrate that centrosome amplification,
      a structural alteration of the cytoskeleton, can promote features of malignant
      transformation. 

PMID- 24739974
TI  - A Palaeozoic shark with osteichthyan-like branchial arches.
AB  - The evolution of serially arranged, jointed endoskeletal supports internal to the
      gills--the visceral branchial arches--represents one of the key events in early
      jawed vertebrate (gnathostome) history, because it provided the morphological
      basis for the subsequent evolution of jaws. However, until now little was known
      about visceral arches in early gnathostomes, and theories about gill arch
      evolution were driven by information gleaned mostly from both modern
      cartilaginous (chondrichthyan) and bony (osteichthyan) fishes. New fossil
      discoveries can profoundly affect our understanding of evolutionary history, by
      revealing hitherto unseen combinations of primitive and derived characters. Here
      we describe a 325 million year (Myr)-old Palaeozoic shark-like fossil that
      represents, to our knowledge, the earliest identified chondrichthyan in which the
      complete gill skeleton is three-dimensionally preserved in its natural position.
      Its visceral arch arrangement is remarkably osteichthyan-like, suggesting that
      this may represent the common ancestral condition for crown gnathostomes. Our
      findings thus reinterpret the polarity of some arch features of the crown jawed
      vertebrates and invert the classic hypothesis, in which modern sharks retain the
      ancestral condition. This study underscores the importance of early
      chondrichthyans in resolving the evolutionary history of jawed vertebrates.

PMID- 24739975
TI  - Scalable control of mounting and attack by Esr1+ neurons in the ventromedial
      hypothalamus.
AB  - Social behaviours, such as aggression or mating, proceed through a series of
      appetitive and consummatory phases that are associated with increasing levels of
      arousal. How such escalation is encoded in the brain, and linked to behavioural
      action selection, remains an unsolved problem in neuroscience. The ventrolateral
      subdivision of the murine ventromedial hypothalamus (VMHvl) contains neurons
      whose activity increases during male-male and male-female social encounters. Non
      cell-type-specific optogenetic activation of this region elicited attack
      behaviour, but not mounting. We have identified a subset of VMHvl neurons marked
      by the oestrogen receptor 1 (Esr1), and investigated their role in male social
      behaviour. Optogenetic manipulations indicated that Esr1(+) (but not Esr1(-))
      neurons are sufficient to initiate attack, and that their activity is
      continuously required during ongoing agonistic behaviour. Surprisingly, weaker
      optogenetic activation of these neurons promoted mounting behaviour, rather than
      attack, towards both males and females, as well as sniffing and close
      investigation. Increasing photostimulation intensity could promote a transition
      from close investigation and mounting to attack, within a single social
      encounter. Importantly, time-resolved optogenetic inhibition experiments revealed
      requirements for Esr1(+) neurons in both the appetitive (investigative) and the
      consummatory phases of social interactions. Combined optogenetic activation and
      calcium imaging experiments in vitro, as well as c-Fos analysis in vivo,
      indicated that increasing photostimulation intensity increases both the number of
      active neurons and the average level of activity per neuron. These data suggest
      that Esr1(+) neurons in VMHvl control the progression of a social encounter from
      its appetitive through its consummatory phases, in a scalable manner that
      reflects the number or type of active neurons in the population. 

PMID- 24739976
TI  - Orally administrated ascorbic acid suppresses neuronal damage and modifies
      expression of SVCT2 and GLUT1 in the brain of diabetic rats with cerebral
      ischemia-reperfusion.
AB  - Diabetes mellitus is known to exacerbate cerebral ischemic injury. In the present
      study, we investigated antiapoptotic and anti-inflammatory effects of oral
      supplementation of ascorbic acid (AA) on cerebral injury caused by middle
      cerebral artery occlusion and reperfusion (MCAO/Re) in rats with streptozotocin
      induced diabetes. We also evaluated the effects of AA on expression of sodium
      dependent vitamin C transporter 2 (SVCT2) and glucose transporter 1 (GLUT1) after
      MCAO/Re in the brain. The diabetic state markedly aggravated MCAO/Re-induced
      cerebral damage, as assessed by infarct volume and edema. Pretreatment with AA
      (100 mg/kg, p.o.) for two weeks significantly suppressed the exacerbation of
      damage in the brain of diabetic rats. AA also suppressed the production of
      superoxide radical, activation of caspase-3, and expression of proinflammatory
      cytokines (tumor necrosis factor-alpha and interleukin-1beta) in the ischemic
      penumbra. Immunohistochemical staining revealed that expression of SVCT2 was
      upregulated primarily in neurons and capillary endothelial cells after MCAO/Re in
      the nondiabetic cortex, accompanied by an increase in total AA (AA +
      dehydroascorbic acid) in the tissue, and that these responses were suppressed in
      the diabetic rats. AA supplementation to the diabetic rats restored these
      responses to the levels of the nondiabetic rats. Furthermore, AA markedly
      upregulated the basal expression of GLUT1 in endothelial cells of nondiabetic and
      diabetic cortex, which did not affect total AA levels in the cortex. These
      results suggest that daily intake of AA attenuates the exacerbation of cerebral
      ischemic injury in a diabetic state, which may be attributed to anti-apoptotic
      and anti-inflammatory effects via the improvement of augmented oxidative stress
      in the brain. AA supplementation may protect endothelial function against the
      exacerbated ischemic oxidative injury in the diabetic state and improve AA
      transport through SVCT2 in the cortex.

PMID- 24739977
TI  - Analysis of wheat prolamins, the causative agents of celiac sprue, using reversed
      phase high performance liquid chromatography (RP-HPLC) and matrix-assisted laser
      desorption ionization time of flight mass spectrometry (MALDI-TOF-MS).
AB  - Wheat prolamins, commonly known as "gluten", are a complex mixture of 71-78
      proteins, which constitute ~80% of the proteins in the wheat grains and supply
      50% of the global dietary protein demand. Prolamins are also responsible for
      numerous gluten-induced disorders and determine the unique visco-elastic
      properties of the wheat dough. These properties necessitate the reliable
      determination of the prolamin composition in wheat grains and their derived
      products. Therefore, this study examined the impact of HPLC conditions, including
      column type, column temperature, flow rate, and the gradient of polar and non
      polar solvents in the mobile phase, to improve the analytical resolution of
      prolamins. The following conditions were found optimal for analyses: column
      temperature 60  degrees C, flow rate 1.0 mL/min and an elution gradient of 20%
      60% of 0.1% trifluoroacetic acid + acetonitrile in 60 min. For further
      improvement of resolution, gliadin and glutenin extracts were analyzed using
      MALDI-TOF-MS in combination with HPLC fractionation. Two semi-quantitative
      methods, densitometry of stained polyacrylamide gels and HPLC, were used to
      determine relative prolamin quantities and the correspondence between the methods
      was established. The combinatorial gluten analyses approach developed during the
      present study was used to analyze prolamin profiles of wheat transformants
      expressing DEMETER silencing artificial microRNA, and the results are discussed.

PMID- 24739978
TI  - Safety and immunogenicity of a vero cell culture-derived whole-virus H5N1
      influenza vaccine in chronically ill and immunocompromised patients.
AB  - The development of vaccines against H5N1 influenza A viruses is a cornerstone of
      pandemic preparedness. Clinical trials of H5N1 vaccines have been undertaken in
      healthy subjects, but studies in risk groups have been lacking. In this study,
      the immunogenicity and safety of a nonadjuvanted cell culture-derived whole-virus
      H5N1 vaccine were assessed in chronically ill and immunocompromised adults.
      Subjects received two priming immunizations with a clade 1 A/Vietnam H5N1
      influenza vaccine, and a subset also received a booster immunization with a clade
      2.1 A/Indonesia H5N1 vaccine 12 to 24 months later. The antibody responses in the
      two populations were assessed by virus neutralization and single radial hemolysis
      assays. The T-cell responses in a subset of immunocompromised patients were
      assessed by enzyme-linked immunosorbent spot assay (ELISPOT). The priming and the
      booster vaccinations were safe and well tolerated in the two risk populations,
      and adverse reactions were predominantly mild and transient. The priming
      immunizations induced neutralizing antibody titers of >=1:20 against the
      A/Vietnam strain in 64.2% of the chronically ill and 41.5% of the
      immunocompromised subjects. After the booster vaccination, neutralizing antibody
      titers of >=1:20 against the A/Vietnam and A/Indonesia strains were achieved in
      77.5% and 70.8%, respectively, of chronically ill subjects and in 71.6% and
      67.5%, respectively, of immunocompromised subjects. The T-cell responses against
      the two H5N1 strains increased significantly over the baseline values.
      Substantial heterosubtypic T-cell responses were elicited against the 2009
      pandemic H1N1 virus and seasonal A(H1N1), A(H3N2), and B subtypes. There was a
      significant correlation between T-cell responses and neutralizing antibody
      titers. These data indicate that nonadjuvanted whole-virus cell culture-derived
      H5N1 influenza vaccines are suitable for immunizing chronically ill and
      immunocompromised populations. (This study is registered at ClinicalTrials.gov
      under registration no. NCT00711295.). 

PMID- 24739979
TI  - Serological diagnostic assays for HIV-associated tuberculosis in sub-Saharan
      Africa?
AB  - In this issue of Clinical and Vaccine Immunology, Siev and colleagues present an
      evaluation of antibody responses to four immunodominant proteins of Mycobacterium
      tuberculosis in patients with HIV-associated pulmonary tuberculosis (TB) in South
      Africa (M. Siev, D. Wilson, S. Kainth, V. O. Kasprowicz, C. M. Feintuch, E. Jenny
      Avital, and J. J. Achkar, 21:791-798, 2014,
      doi:http://dx.doi.org/10.1128/CVI.00805-13). This commentary discusses the
      enormous need for simple point-of-care assays for tuberculosis (TB) diagnosis in
      patients with and without HIV coinfection in high-burden settings and considers
      the potential role of serological assays and the huge challenges inherent in
      developing and validating such assays. 

PMID- 24739981
TI  - Acquisition of carbapenemase-producing Enterobacteriaceae by healthy travellers
      to India, France, February 2012 to March 2013.
AB  - Healthy travellers to countries where carbapenemases-producing Enterobacteriaceae
      (CPE) are endemic might be at risk for their acquisition, even without contact
      with the local healthcare system. Here, we report the acquisition of CPE (two OXA
      181, one New Delhi metallo-beta-lactamase 1 (NDM-1)) in three healthy travellers
      returning from India. The duration of CPE intestinal carriage was less than one
      month. The results indicate that healthy travellers recently returning from India
      might be considered as at risk for CPE carriage.

PMID- 24739980
TI  - Assessment of chimpanzee adenovirus serotype 63 neutralizing antibodies prior to
      evaluation of a candidate malaria vaccine regimen based on viral vectors.
AB  - Prior to a chimpanzee adenovirus-based (ChAd63) malarial vaccine trial, sera were
      collected to assess ChAd63-specific neutralizing antibody titers in Banfora
      (Burkina Faso). The low neutralizing antibody titers reported in both adults and
      children (median titers, 139.1 and 35.0, respectively) are encouraging for the
      potential use of ChAd63 as a malarial vaccine vector. 

PMID- 24739982
TI  - Potential for Zika virus transmission through blood transfusion demonstrated
      during an outbreak in French Polynesia, November 2013 to February 2014.
AB  - Since October 2013, French Polynesia has experienced the largest documented
      outbreak of Zika virus (ZIKAV) infection. To prevent transmission of ZIKAV by
      blood transfusion, specific nucleic acid testing of blood donors was implemented.
      From November 2013 to February 2014: 42 (3%) of 1,505 blood donors, although
      asymptomatic at the time of blood donation, were found positive for ZIKAV by PCR.
      Our results serve to alert blood safety authorities about the risk of post
      transfusion Zika fever.

PMID- 24739983
TI  - Results of surveillance for infections with Shiga toxin-producing Escherichia
      coli (STEC) of serotype O104:H4 after the large outbreak in Germany, July to
      December 2011.
AB  - After the massive outbreak of infections with Shiga toxin-producing Escherichia
      coli (STEC) of serotype O104:H4 in Germany in the summer of 2011, post-outbreak
      surveillance for further infections with this type of STEC was maintained until
      the end of 2011. This surveillance was based on national mandatory reporting of
      STEC infections and the associated complication of haemolytic uraemic syndrome
      (HUS), as well as on data obtained from a questionnaire. Between the outbreak's
      end (5 July) and 31 December 2011, a total of 33 post-outbreak cases were
      recorded. Post-outbreak cases occurred with diminishing frequency towards the
      year's end and resembled the outbreak cases in many respects, however the
      proportion of HUS among all post-outbreak cases was smaller than during the
      outbreak. Two thirds of the post-outbreak cases were likely infected by contact
      with known outbreak cases. Both laboratory and nosocomial spread was noted in
      this period. No post-outbreak case recalled sprout consumption as a potential
      source of infection. The scarcity of information conveyed by the nonculture tests
      routinely used in Germany to diagnose STEC made linkage of post-outbreak cases to
      the outbreak difficult. Though post-outbreak surveillance demonstrated the
      outbreak strain's potential for lengthy chains of transmission aided by prolonged
      shedding, our results and continued routine surveillance until the end of 2013 do
      not support the notion, that the outbreak strain has been able to establish
      itself in the German environment.

PMID- 24739984
TI  - Two decades of successes and failures in controlling the transmission of HIV
      through injecting drug use in England and Wales, 1990 to 2011.
AB  - Responses to injecting drug use have changed focus over the last 20 years.
      Prevalence and incidence of human immunodeficiency virus (HIV) among people who
      inject drugs (PWID) in England and Wales were examined in relation to these
      changes. A voluntary unlinked-anonymous surveillance study obtained a biological
      sample and questionnaire data from PWID through annual surveys since 1990.
      Prevalence and incidence trends were estimated via generalised linear models, and
      compared with a policy time-line. Overall HIV prevalence among 38,539
      participations was 1.15%. Prevalence was highest among those who started
      injecting before 1985; throughout the 1990s, prevalence fell in this group and
      was stable among those who started injecting later. Prevalence was higher in 2005
      than 2000 (odds ratio: 3.56 (95% confidence interval (CI) 1.40-9.03) in London,
      3.40 (95% CI 2.31-5.02) elsewhere). Estimated HIV incidence peaked twice, around
      1983 and 2005. HIV was an important focus of policy concerning PWID from 1984
      until 1998. This focus shifted at a time when drug use and risk were changing.
      The increased incidence in 2005 cannot be ascribed to the policy changes, but
      these appeared to be temporally aligned. Policy related to PWID should be
      continually reviewed to ensure rapid responses to increased risk.

PMID- 24739986
TI  - EFSA launches call for expressions of interest for scientific committee and
      scientific panels.

PMID- 24739992
TI  - Issues in the diagnosis and management of the papilledema shunt.
AB  - BACKGROUND: Dural arteriovenous fistulas (DAVFs) that shunt blood into the
      transverse or superior sagittal venous sinuses cause papilledema by raising
      intracranial pressure ("the papilledema shunt"). Such fistulas pose unique
      diagnostic and therapeutic challenges. METHODS: Case report and literature
      review. RESULTS: In a patient presenting with papilledema, non-invasive brain
      vascular imaging disclosed subtle signs of a DAVF. Digital angiography delineated
      the DAVF and revealed cortical venous reflux. After three transarterial
      embolizations with ethylene vinyl alcohol, the DAVF was closed and papilledema
      resolved. CONCLUSIONS: The imaging features of a DAVF that cause papilledema may
      be subtle on non-invasive vascular imaging. If overlooked, and lumbar puncture is
      performed, there is a substantial risk of brain herniation. Cortical venous
      reflux, which may be relatively common in these DAVFs, impels the need for
      endovascular closure. The transvenous route, often employed for closing cavernous
      sinus DAVFs, should be avoided because of the dangers of dural venous sinus
      thrombosis.

PMID- 24739991
TI  - Revitalizing personalized medicine: respecting biomolecular complexities beyond
      gene expression.
AB  - Despite recent advancements in "omic" technologies, personalized medicine has not
      realized its fullest potential due to isolated and incomplete application of gene
      expression tools. In many instances, pharmacogenomics is being interchangeably
      used for personalized medicine, when actually it is one of the many facets of
      personalized medicine. Herein, we highlight key issues that are hampering the
      advancement of personalized medicine and highlight emerging predictive tools that
      can serve as a decision support mechanism for physicians to personalize
      treatments. 

PMID- 24739994
TI  - A direct comparison of onabotulinumtoxina (Botox) and IncobotulinumtoxinA
      (Xeomin) in the treatment of benign essential blepharospasm: a split-face
      technique.
AB  - BACKGROUND: Benign essential blepharospasm (BEB) is characterized by progressive
      involuntary contractions of the protractor muscles, sometimes leading to a
      debilitating closure of the lids. It is currently treated with the injection of
      botulinum neurotoxin A (BoNT/A). The purpose of this study was to compare 2
      BoNT/A preparations (i.e., Xeomin and Botox) in the treatment of BEB. METHODS:
      This was a prospective, randomized, double-blinded split-face technique in 48
      patients already treated by Botox for BEB. Patients received the same medication
      to either side of the face for 4 injections, and were then evaluated using
      subjective and objective measures. Blepharospasm Disability Index (BSDI) and
      Jankovic Rating Scale (JRS) were assessed using a repeated-measures analysis of
      variance (ANOVA) and paired t test. Patient preference and objective comparison
      of residual orbicularis strength and spasm were compared using a multinomial
      logistic regression model, a repeated-measures ANOVA, and a paired t test.
      RESULTS: A paired t test showed no preference between Xeomin and Botox (P =
      0.7205) and demonstrated a tendency toward not having a preference for either
      medication (P = 0.0301 vs Botox and P = 0.0039 vs Xeomin). The regression model
      showed no effect of time on patient preference (P = 0.4217). The ANOVA for BSDI
      scores did not reveal any difference between the 2 medications as compared with
      baseline (P = 0.8161), nor did it demonstrate an effect of time on BSDI scores (P
      = 0.6108). A paired t test found no difference between the 2 scores (P = 0.1909)
      at baseline. There was no difference in JRS scores for either medication when
      compared with baseline (P = 0.2314), nor was there an effect of time on such
      scores (P = 0.4951). There was also no difference between the 2 medications
      according to paired t test (P = 0.3224) at baseline. Baseline residual
      orbicularis strength was similar between the 2 medications (paired t test; P =
      0.3228). ANOVA shows an effect of time on orbicularis strength (P = 0.0055), but
      no difference was seen at any of the 5 visits (P > 0.05). Baseline spasm scores
      were similar between Botox and Xeomin (paired Student t test; P = 0.3228). The
      ANOVA shows no difference between both medications at any point in time (P =
      0.4408), and that time had no effect on the efficacy of either treatment (P =
      0.3268). CONCLUSION: No difference between Xeomin and Botox was detected in
      either subjective or objective measures for the treatment of BEB.

PMID- 24739995
TI  - Lateral geniculate lesions causing reversible blindness in a pre-eclamptic
      patient with a variant of posterior reversible encephalopathy syndrome.
AB  - Bilateral lateral geniculate nucleus (LGN) injury is a rare cause of vision loss.
      We describe a patient with pre-eclampsia who developed profound but reversible
      bilateral vision loss, bilateral serous retinal detachments, and magnetic
      resonance imaging signs of a variant of posterior reversible encephalopathy
      syndrome (PRES) that affected both LGNs and spared the retrogeniculate pathways.
      We provide evidence that the visual loss was not from the chorioretinal lesions
      but from the LGN lesions. The concurrence of PRES and lesions attributed to
      choroidal hypoperfusion provides support for the notion that vasoconstriction
      also underlies the pathogenesis of PRES.

PMID- 24739993
TI  - The idiopathic intracranial hypertension treatment trial: design considerations
      and methods.
AB  - BACKGROUND: The objectives of this study were to present the rationale for the
      main aspects of the study design and describe the trial methodology for the
      Idiopathic Intracranial Hypertension Treatment Trial (IIHTT). METHODS: Eligible
      candidates with mild visual field loss (automated perimetric mean deviation [PMD]
      -2 to -7 dB) were randomized to receive either acetazolamide or matching placebo
      tablets. Randomized participants were offered participation in a supervised
      dietary program. The primary outcome variable, PMD, was measured at 6 months.
      Additionally, cerebrospinal fluid from subjects and serum from study participants
      and matched controls were collected for genetic analysis and vitamin A studies.
      An ancillary optical coherence substudy was added to investigate the changes of
      papilledema in the optic nerve head and retina that correlate with Frisen
      grading, visual field deficits, and low-contrast visual acuity. RESULTS: The
      randomized trial entered 165 participants from March 17, 2010, through November
      27, 2012, from the United States and Canada. The primary outcome (month 6) visits
      were successfully completed by June 15, 2013. Blood specimens were obtained from
      165 controls without IIH to investigate vitamin A metabolism and genetic markers
      of potential risk factors for IIH. CONCLUSIONS: The IIHTT is the first
      randomized, double-masked placebo-controlled trial to study the effectiveness of
      medical treatment for patients with IIH.

PMID- 24739998
TI  - The oldest caseid synapsid from the Late Pennsylvanian of Kansas, and the
      evolution of herbivory in terrestrial vertebrates.
AB  - The origin and early evolution of amniotes (fully terrestrial vertebrates) led to
      major changes in the structure and hierarchy of terrestrial ecosystems. The first
      appearance of herbivores played a pivotal role in this transformation. After an
      early bifurcation into Reptilia and Synapsida (including mammals) 315 Ma,
      synapsids dominated Paleozoic terrestrial vertebrate communities, with the
      herbivorous caseids representing the largest vertebrates on land. Eocasea martini
      gen. et sp. nov., a small carnivorous caseid from the Late Carboniferous, extends
      significantly the fossil record of Caseidae, and permits the first clade-based
      study of the origin and initial evolution of herbivory in terrestrial tetrapods.
      Our results demonstrate for the first time that large caseid herbivores evolved
      from small, non-herbivorous caseids. This pattern is mirrored by three other
      clades, documenting multiple, independent, but temporally staggered origins of
      herbivory and increase in body size among early terrestrial tetrapods, leading to
      patterns consistent with modern terrestrial ecosystem. 

PMID- 24739997
TI  - Noncoding RNAs: new players in chronic pain.
AB  - Chronic pain, a common clinical symptom, is often treated inadequately or
      ineffectively in part due to the incomplete understanding of molecular mechanisms
      that initiate and maintain this disorder. Newly identified noncoding RNAs govern
      gene expression. Recent studies have shown that peripheral noxious stimuli drive
      expressional changes in noncoding RNAs and that these changes are associated with
      pain hypersensitivity under chronic pain conditions. This review first presents
      current evidence for the peripheral inflammation/nerve injury-induced change in
      the expression of two types of noncoding RNAs, microRNAs, and Kcna2 antisense
      RNA, in pain-related regions, particularly in the dorsal root ganglion. The
      authors then discuss how peripheral noxious stimuli induce such changes. The
      authors finally explore potential mechanisms of how expressional changes in
      dorsal root ganglion microRNAs and Kcna2 antisense RNA contribute to the
      development and maintenance of chronic pain. An understanding of these mechanisms
      may propose novel therapeutic strategies for preventing and/or treating chronic
      pain. 

PMID- 24739996
TI  - Intubation biomechanics: laryngoscope force and cervical spine motion during
      intubation with Macintosh and Airtraq laryngoscopes.
AB  - INTRODUCTION: Laryngoscopy and endotracheal intubation in the presence of
      cervical spine instability may put patients at risk of cervical cord injury.
      Nevertheless, the biomechanics of intubation (cervical spine motion as a function
      of applied force) have not been characterized. This study characterized and
      compared the relationship between laryngoscope force and cervical spine motion
      using two laryngoscopes hypothesized to differ in force. METHODS: Fourteen adults
      undergoing elective surgery were intubated twice (Macintosh, Airtraq). During
      each intubation, laryngoscope force, cervical spine motion, and glottic view were
      recorded. Force and motion were referenced to a preintubation baseline (stage 1)
      and were characterized at three stages: stage 2 (laryngoscope introduction);
      stage 3 (best glottic view); and stage 4 (endotracheal tube in trachea). RESULTS:
      Maximal force and motion occurred at stage 3 and differed between the Macintosh
      and Airtraq: (1) force: 48.8 +/- 15.8 versus 10.4 +/- 2.8 N, respectively, P =
      0.0001; (2) occiput-C5 extension: 29.5 +/- 8.5 versus 19.1 +/- 8.7 degrees,
      respectively, P = 0.0023. Between stages 2 and 3, the motion/force ratio differed
      between Macintosh and Airtraq: 0.5 +/- 0.2 versus 2.0 +/- 1.4 degrees/N,
      respectively; P = 0.0006. DISCUSSION: The relationship between laryngoscope force
      and cervical spine motion is: (1) nonlinear and (2) differs between
      laryngoscopes. Differences between laryngoscopes in motion/force relationships
      are likely due to: (1) laryngoscope-specific cervical extension needed for
      intubation, (2) laryngoscope-specific airway displacement/deformation needed for
      intubation, and (3) cervical spine and airway tissue viscoelastic properties.
      Cervical spine motion during endotracheal intubation is not directly proportional
      to force. Low-force laryngoscopes cannot be assumed to result in proportionally
      low cervical spine motion.

PMID- 24739999
TI  - Quantum dots on vertically aligned gold nanorod monolayer: plasmon enhanced
      fluorescence.
AB  - CTAB-coated Au nanorods were directly self-assembled into a vertically aligned
      monolayer with highly uniform hot spots through a simple but robust approach. By
      coupling with CdSe/ZnS quantum dots, a maximum enhancement of 10.4 is achieved
      due to: increased excitation transition rate, radiative rate, and coupling
      efficiency of emission to the far field. 

PMID- 24740000
TI  - Production of a Brassica napus Low-Molecular Mass Acyl-Coenzyme A-Binding Protein
      in Arabidopsis Alters the Acyl-Coenzyme A Pool and Acyl Composition of Oil in
      Seeds.
AB  - Low-molecular mass (10 kD) cytosolic acyl-coenzyme A-binding protein (ACBP) has a
      substantial influence over fatty acid (FA) composition in oilseeds, possibly via
      an effect on the partitioning of acyl groups between elongation and desaturation
      pathways. Previously, we demonstrated that the expression of a Brassica napus
      ACBP (BnACBP) complementary DNA in the developing seeds of Arabidopsis
      (Arabidopsis thaliana) resulted in increased levels of polyunsaturated FAs at the
      expense of eicosenoic acid (20:1cisDelta11) and saturated FAs in seed oil. In
      this study, we investigated whether alterations in the FA composition of seed oil
      at maturity were correlated with changes in the acyl-coenzyme A (CoA) pool in
      developing seeds of transgenic Arabidopsis expressing BnACBP. Our results
      indicated that both the acyl-CoA pool and seed oil of transgenic Arabidopsis
      lines expressing cytosolic BnACBP exhibited relative increases in linoleic acid
      (18:2cisDelta9,12; 17.9%-44.4% and 7%-13.2%, respectively) and decreases in
      20:1cisDelta11 (38.7%-60.7% and 13.8%-16.3%, respectively). However, alterations
      in the FA composition of the acyl-CoA pool did not always correlate with those
      seen in the seed oil. In addition, we found that targeting of BnACBP to the
      endoplasmic reticulum resulted in FA compositional changes that were similar to
      those seen in lines expressing cytosolic BnACBP, with the most prominent
      exception being a relative reduction in alpha-linolenic acid
      (18:3cisDelta9,12,15) in both the acyl-CoA pool and seed oil of the former (48.4%
      48.9% and 5.3%-10.4%, respectively). Overall, these data support the role of ACBP
      in acyl trafficking in developing seeds and validate its use as a
      biotechnological tool for modifying the FA composition of seed oil.

PMID- 24740002
TI  - The effect of laterality and primary tumor site on cancer-specific mortality in
      breast cancer: a SEER population-based study.
AB  - BACKGROUND: Reduced overall survival has been observed in patients with left
      sided versus right-sided breast cancer due to cardiac toxicity after
      radiotherapy. However, the effect of laterality and primary tumor site on breast
      cancer-specific mortality (BCSM) remains unclear. PATIENTS AND METHODS: We
      analyzed data from 305,443 women ages 20- to 79-years-old diagnosed with breast
      cancer between 1990 and 2009. The data were obtained from the population-based
      Surveillance, Epidemiology, and End Results (SEER) program of the U.S. National
      Cancer Institute. The survival outcomes with regard to laterality and primary
      tumor site were compared using univariate and multivariate (Cox proportional
      hazards regression model) methods. RESULTS: In the multivariate analysis, BCSM
      was affected by the primary tumor site (P<0.0001) but not laterality (P = 0.331).
      The combined effect was piecewise: using the left upper-outer quadrant as the
      reference, the BCSM hazard ratio (HR) was not significant in the right upper
      quadrant (P = 0.755) and the right central portion (P = 0.329). The BCSM HR was
      slightly increased in the left central portion as well as the left and right
      lower-outer quadrants (HRs from 1.136 to 1.145; P<0.0001). The BCSM HR was
      significantly increased in the upper-inner and lower-inner quadrants (HRs from
      1.242 to 1.372; P<0.0001) on both sides. Laterality only impacted BCSM in
      patients with breast cancer located in the central portion (HR, 1.100; P = 0.013,
      using the right side as the reference). CONCLUSION: Patients with tumors in the
      upper-outer quadrant of both sides and the right central portion have a better
      prognosis than patients with tumors at other locations. Laterality is not
      regarded as a prognostic factor in breast cancer.

PMID- 24740003
TI  - New norclerodane diterpenoids from the tubers of Dioscorea bulbifera.
AB  - Phytochemical investigations of the tubers of Dioscorea bulbifera L. resulted in
      the isolation of nine norclerodane diterpenoids, including two new compounds,
      diosbulbins N (1) and P (3), a new naturally occurring compound, diosbulbin O
      (2), and six known ones, diosbulbins A-D, F and G (4-9). Their structures were
      established by spectroscopic and chemical methods. The absolute stereochemistry
      of 1 was determined by a modified Mosher's method, and the absolute configuration
      of 2 was determined by a single-crystal X-ray diffraction analysis with CuKalpha
      irradiation. Compounds 1-3 were evaluated for in vitro cytotoxicity against five
      human cancer cell lines. 

PMID- 24740004
TI  - A meta analysis of pancreatic microarray datasets yields new targets as cancer
      genes and biomarkers.
AB  - The lack of specific symptoms at early tumor stages, together with a high
      biological aggressiveness of the tumor contribute to the high mortality rate for
      pancreatic cancer (PC), which has a five year survival rate of less than 5%.
      Improved screening for earlier diagnosis, through the detection of diagnostic and
      prognostic biomarkers provides the best hope of increasing the rate of curatively
      resectable carcinomas. Though many serum markers have been reported to be
      elevated in patients with PC, so far, most of these markers have not been
      implemented into clinical routine due to low sensitivity or specificity. In this
      study, we have identified genes that are significantly upregulated in PC, through
      a meta-analysis of large number of microarray datasets. We demonstrate that the
      biological functions ascribed to these genes are clearly associated with PC and
      metastasis, and that that these genes exhibit a strong link to pathways involved
      with inflammation and the immune response. This investigation has yielded new
      targets for cancer genes, and potential biomarkers for pancreatic cancer. The
      candidate list of cancer genes includes protein kinase genes, new members of gene
      families currently associated with PC, as well as genes not previously linked to
      PC. In this study, we are also able to move towards developing a signature for
      hypomethylated genes, which could be useful for early detection of PC. We also
      show that the significantly upregulated 800+ genes in our analysis can serve as
      an enriched pool for tissue and serum protein biomarkers in pancreatic cancer. 

PMID- 24740005
TI  - Human immune responses to H. pylori HLA Class II epitopes identified by
      immunoinformatic methods.
AB  - H. pylori persists in the human stomach over decades and promotes several adverse
      clinical sequelae including gastritis, peptic ulcers and gastric cancer that are
      linked to the induction and subsequent evasion of chronic gastric inflammation.
      Emerging evidence indicates that H. pylori infection may also protect against
      asthma and some other immune-mediated conditions through regulatory T cell
      effects outside the stomach. To characterize the complexity of the CD4+ T cell
      response generated during H. pylori infection, computational methods were
      previously used to generate a panel of 90 predicted epitopes conserved among H.
      pylori genomes that broadly cover HLA Class II diversity for maximum population
      coverage. Here, these sequences were tested individually for their ability to
      induce in vitro responses in peripheral blood mononuclear cells by interferon
      gamma ELISpot assay. The average number of spot-forming cells/million PBMCs was
      significantly elevated in H. pylori-infected subjects over uninfected persons.
      Ten of the 90 peptides stimulated IFN-gamma secretion in the H. pylori-infected
      group only, whereas two out of the 90 peptides elicited a detectable IFN-gamma
      response in the H. pylori-uninfected subjects but no response in the H. pylori
      infected group. Cytokine ELISA measurements performed using in vitro PBMC culture
      supernatants demonstrated significantly higher levels of TNF-alpha, IL-2, IL-4,
      IL-6, IL-10, and TGF-beta1 in the H. pylori-infected subjects, whereas IL-17A
      expression was not related to the subjects H. pylori-infection status. Our
      results indicate that the human T cell responses to these 90 peptides are
      generally increased in actively H. pylori-infected, compared with H. pylori
      naive, subjects. This information will improve understanding of the complex
      immune response to H. pylori, aiding rational epitope-driven vaccine design as
      well as helping identify other H. pylori epitopes with potentially
      immunoregulatory effects. 

PMID- 24740007
TI  - Integrating reductive and synthetic approaches in biology using man-made cell
      like compartments.
AB  - We propose 'integrated synthetic genetics' as a novel methodology that integrates
      reductive and synthetic approaches used in life science research. Integrated
      synthetic genetics enables determinations of sets of genes required for the
      functioning of any biological subsystem. This method utilizes artificial cell
      like compartments, including a randomly introduced whole gene library, strictly
      defined components for in vitro transcription and translation and a reporter that
      fluoresces 'only when a particular function of a target biological subsystem is
      active.' The set of genes necessary for the target biological subsystem can be
      identified by isolating fluorescent artificial cells and multiplex next
      generation sequencing of genes included in these cells. The importance of this
      methodology is that screening for the set of genes involved in a subsystem and
      reconstructing the entire subsystem can be done simultaneously. This methodology
      can be applied to any biological subsystem of any species and may remarkably
      accelerate life science research. 

PMID- 24740009
TI  - Heat and mass transfer through interfaces of nanosized bubbles/droplets: the
      influence of interface curvature.
AB  - Heat and mass transfer through interfaces is central in nucleation theory,
      nanotechnology and many other fields of research. Heat transfer in nanoparticle
      suspensions and nanoporous materials displays significant and opposite
      correlations with particle and pore size. We investigate these effects further
      for transfer of heat and mass across interfaces of bubbles and droplets with
      radii down to 2 nm. We use square gradient theory at and beyond equilibrium to
      calculate interfacial resistances in single-component and two-component systems.
      Interface resistances, as defined by non-equilibrium thermodynamics, vary
      continuously with the interface curvature, from negative (bubbles) to zero
      (planar interface) to positive (droplet) values. The interface resistances of 2
      nm radii bubbles/droplets are in some cases one order of magnitude different from
      those of the planar interface. The square gradient model predicts that the
      thermal interface resistances of droplets decrease with particle size, in
      accordance with results from the literature, only if the peak in the local
      resistivity is shifted toward the vapor phase. The curvature will then have an
      opposite effect on the resistance of bubbles and droplets. The model predicts
      that the coupling between heat and mass fluxes, when quantified as the heat of
      transfer of the interface, is of the same order of magnitude as the enthalpy
      change across the interface, and depends much less on curvature than the
      interface resistances. 

PMID- 24740008
TI  - Basic helix-loop-helix transcription factor Bmsage is involved in regulation of
      fibroin H-chain gene via interaction with SGF1 in Bombyx mori.
AB  - Silk glands are specialized in the synthesis of several secretory proteins.
      Expression of genes encoding the silk proteins in Bombyx mori silk glands with
      strict territorial and developmental specificities is regulated by many
      transcription factors. In this study, we have characterized B. mori sage, which
      is closely related to sage in the fruitfly Drosophila melanogaster. It is termed
      Bmsage; it encodes transcription factor Bmsage, which belongs to the Mesp
      subfamily, containing a basic helix-loop-helix motif. Bmsage transcripts were
      detected specifically in the silk glands of B. mori larvae through RT-PCR
      analysis. Immunoblotting analysis confirmed the Bmsage protein existed
      exclusively in B. mori middle and posterior silk gland cells. Bmsage has a low
      level of expression in the 4th instar molting stages, which increases gradually
      in the 5th instar feeding stages and then declines from the wandering to the
      pupation stages. Quantitative PCR analysis suggested the expression level of
      Bmsage in a high silk strain was higher compared to a lower silk strain on day 3
      of the larval 5th instar. Furthermore, far western blotting and co
      immunoprecipitation assays showed the Bmsage protein interacted with the fork
      head transcription factor silk gland factor 1 (SGF1). An electrophoretic mobility
      shift assay showed the complex of Bmsage and SGF1 proteins bound to the A and B
      elements in the promoter of fibroin H-chain gene(fib-H), respectively. Luciferase
      reporter gene assays confirmed the complex of Bmsage and SGF1 proteins increased
      the expression of fib-H. Together, these results suggest Bmsage is involved in
      the regulation of the expression of fib-H by being together with SGF1 in B. mori
      PSG cells. 

PMID- 24740010
TI  - Proteomics approaches for identification of tumor relevant protein targets in
      pulmonary squamous cell carcinoma by 2D-DIGE-MS.
AB  - Potential markers for progression of pulmonary squamous cell carcinoma (SCC) were
      identified by examining samples of lung SCC and adjacent normal tissues using a
      combination of fluorescence two-dimensional difference gel electrophoresis (2D
      DIGE), matrix-assisted laser desorption/ionization time of flight mass
      spectrometry (MALDI-TOF-MS), and electrospray ionization quadrupole-time of
      flight mass spectrometry (ESI-Q-TOF). The PANTHER System was used for gel image
      based quantification and statistical analysis. An analysis of proteomic data
      revealed that 323 protein spots showed significantly different levels of
      expression (P <= 0.05) in lung SCC tissue compared to expression in normal lung
      tissue. A further analysis of these protein spots by MALDI-TOF-MS identified 81
      different proteins. A systems biology approach was used to map these proteins to
      major pathways involved in numerous cellular processes, including localization,
      transport, cellular component organization, apoptosis, and reproduction.
      Additionally, the expression of several proteins in lung SCC and normal tissues
      was examined using immunohistochemistry and western blot. The functions of
      individual proteins are being further investigated and validated, and the results
      might provide new insights into the mechanism of lung SCC progression,
      potentially leading to the design of novel diagnostic and therapeutic strategies.

PMID- 24740012
TI  - Global analysis of critical care burden.

PMID- 24740013
TI  - Reducing ZnO nanoparticle cytotoxicity by surface modification.
AB  - Nanoparticulate zinc oxide (ZnO) is one of the most widely used engineered
      nanomaterials and its toxicology has gained considerable recent attention. A key
      aspect for controlling biological interactions at the nanoscale is understanding
      the relevant nanoparticle surface chemistry. In this study, we have determined
      the disposition of ZnO nanoparticles within human immune cells by measurement of
      total Zn, as well as the proportions of extra- and intracellular dissolved Zn as
      a function of dose and surface coating. From this mass balance, the intracellular
      soluble Zn levels showed little difference in regard to dose above a certain
      minimal level or to different surface coatings. PEGylation of ZnO NPs reduced
      their cytotoxicity as a result of decreased cellular uptake arising from a
      minimal protein corona. We conclude that the key role of the surface properties
      of ZnO NPs in controlling cytotoxicity is to regulate cellular nanoparticle
      uptake rather than altering either intracellular or extracellular Zn dissolution.

PMID- 24740014
TI  - Detection of freezing of gait in Parkinson disease: preliminary results.
AB  - Freezing of gait (FOG) is a common symptom in Parkinsonism, which affects the
      gait pattern and is associated to a fall risk. Automatized FOG episode detection
      would allow systematic assessment of patient state and objective evaluation of
      the clinical effects of treatments. Techniques have been proposed in the
      literature to identify FOG episodes based on the frequency properties of inertial
      sensor signals. Our objective here is to adapt and extend these FOG detectors in
      order to include other associated gait pattern changes, like festination. The
      proposed approach is based on a single wireless inertial sensor placed on the
      patient's lower limbs. The preliminary experimental results show that existing
      frequency-based freezing detectors are not sufficient to detect all FOG and
      festination episodes and that the observation of some gait parameters such as
      stride length and cadence are valuable inputs to anticipate the occurrence of
      upcoming FOG events. 

PMID- 24740016
TI  - Patients' perceptions of care are associated with quality of hospital care: a
      survey of 4605 hospitals.
AB  - Favorable patient experience and low complication rates have been proposed as
      essential components of patient-centered medical care. Patients' perception of
      care is a key performance metric and is used to determine payments to hospitals.
      It is unclear if there is a correlation between technical quality of care and
      patient satisfaction. The study authors correlated patient perceptions of care
      measured by the Hospital Consumer Assessment of Healthcare Providers and Systems
      scores with accepted quality of care indicators. The Hospital Compare database
      (4605 hospitals) was used to examine complication rates and patient-reported
      experience for hospitals across the nation in 2011. The majority of the
      correlations demonstrated an inverse relationship between patient experience and
      complication rates. This negative correlation suggests that reducing these
      complications can lead to a better hospital experience. Overall, these results
      suggest that patient experience is generally correlated with the quality of care
      provided. 

PMID- 24740015
TI  - Myeloid-specific Rictor deletion induces M1 macrophage polarization and
      potentiates in vivo pro-inflammatory response to lipopolysaccharide.
AB  - The phosphoinositide-3-kinase (PI3K)/protein kinase B (Akt) axis plays a central
      role in attenuating inflammation upon macrophage stimulation with toll-like
      receptor (TLR) ligands. The mechanistic target of rapamycin complex 2 (mTORC2)
      relays signal from PI3K to Akt but its role in modulating inflammation in vivo
      has never been investigated. To evaluate the role of mTORC2 in the regulation of
      inflammation in vivo, we have generated a mouse model lacking Rictor, an
      essential mTORC2 component, in myeloid cells. Primary macrophages isolated from
      myeloid-specific Rictor null mice exhibited an exaggerated response to TLRs
      ligands, and expressed high levels of M1 genes and lower levels of M2 markers. To
      determine whether the loss of Rictor similarly affected inflammation in vivo,
      mice were either fed a high fat diet, a situation promoting chronic but low-grade
      inflammation, or were injected with lipopolysaccharide (LPS), which mimics an
      acute, severe septic inflammatory condition. Although high fat feeding
      contributed to promote obesity, inflammation, macrophage infiltration in adipose
      tissue and systemic insulin resistance, we did not observe a significant impact
      of Rictor loss on these parameters. However, mice lacking Rictor exhibited a
      higher sensitivity to septic shock when injected with LPS. Altogether, these
      results indicate that mTORC2 is a key negative regulator of macrophages TLR
      signalling and that its role in modulating inflammation is particularly important
      in the context of severe inflammatory challenges. These observations suggest that
      approaches aimed at modulating mTORC2 activity may represent a possible
      therapeutic approach for diseases linked to excessive inflammation.

PMID- 24740017
TI  - Treatment for Necrotizing Soft-Tissue Infections: More Skin in the Game.

PMID- 24740018
TI  - The third dedicated CSPS annals.

PMID- 24740019
TI  - Auricular reconstruction with prolonged tissue expansion and porous polyethylene
      implants.
AB  - OBJECTIVE: This study aimed to present our clinical experience using a prolonged
      tissue expansion technique and a Medpor framework for congenital microtia
      reconstruction. METHODS: Auricular reconstruction was performed in 3 surgical
      stages. In the first surgical stage, a 60-mL custom kidney-shaped tissue expander
      is placed subcutaneously in the retroauricular mastoid region. The tissue
      expander is then serially expanded to maximum volume plus 30%. The tissue
      expander is then left fully expanded for 3 to 6 months. In the second surgical
      stage, the tissue expander is removed and a single-piece Medpor implant is placed
      and covered entirely by the expanded skin flap, without application of a fascial
      flap or skin graft. In the third stage, we perform an excision of the remnant
      microtic ear. RESULTS: A total of 15 patients were included with postoperative
      follow-up ranging from 6 months to 5 years. The draped soft tissue envelope was
      thin enough to show the reconstructed ear with excellent definition of the
      framework. Complications in this series included 1 case of partial implant
      exposure. CONCLUSIONS: The use of a Medpor framework after prolonged tissue
      expansion provides a well-defined, well-projected ear with robust soft tissue
      coverage. The expanded skin envelope with this method provides sufficient
      retroauricular non-hair-bearing skin tissues for draping the framework without
      the need for temporoparietal fascial flap or skin grafting. This alternative
      surgical method reduces surgical time and morbidity, and facilitates an
      aesthetic, natural-appearing reconstruction of the auricle.

PMID- 24740021
TI  - Modification of the tube-in-tube pedicled anterolateral thigh flap for total
      phalloplasty: the mushroom flap.
AB  - BACKGROUND: Malformation or absence of the penis can lead to physical and
      psychological problems for male patients. Reconstruction of the phallus should
      optimally be completed in a single procedure, be aesthetically pleasing, retain
      erogenous and tactile sensation, enable micturition in the standing position, and
      allow for penetrative sexual intercourse. The tube-in-tube flap was described
      nearly 30 years ago and forms both a urethra and an outer penile shaft with a
      single flap. Here we present our modification of the original tube-in-tube design
      with the pedicled anterolateral thigh (ALT) flap and an extension for the
      neoglans, which we have termed the "mushroom flap" because of its shape and
      design. METHODS: The flap is based on the ALT flap; however, the area that will
      become the neoglans is shaped with a semicircular extension, resembling the head
      of a mushroom. When the flap is tubularized, the neoglans has the proper anatomic
      landmarks such as the corona and more closely approximates a circumcised penis.
      When used in conjunction with the tube-in-tube design, the neophallus, neoglans,
      and neourethra can all be constructed in a single stage with a single flap.
      RESULTS: We have performed total phalloplasties in three patients using the
      pedicled ALT flap, and the mushroom flap design evolved as we sought to improve
      the aesthetics of the neoglans. In comparing the aesthetic results among our
      patients as well as those published in the literature, the mushroom flap design
      seems to provide the most natural and aesthetically pleasing appearance.
      CONCLUSIONS: The pedicled ALT flap can be used to reconstruct an entire penis, as
      well as a urethra, without the need for microsurgery. By modifying the original
      tube-in-tube design to include a semicircular extension (a.k.a. the "mushroom
      flap"), we feel that we have been able to achieve a more natural-appearing
      neoglans.

PMID- 24740020
TI  - Single-specialty management and reconstruction of necrotizing fasciitis of the
      upper extremities: clinical and economic benefits from a case series.
AB  - PURPOSE: Patients with necrotizing fasciitis are managed with multiple prompt,
      radical surgical debridements and critical care support. Debridement and
      reconstruction are often provided by different surgical teams. Anecdotally,
      single-specialty management seemed to be a more efficient management strategy.
      This study aimed to investigate and compare the outcomes of management by plastic
      surgery versus multiple disciplines through a retrospective economic and clinical
      analysis of patients with necrotizing fasciitis treated over 8 years. We also
      present 3 index cases for which our service functioned as the primary management
      team. METHODS: Necrotizing fasciitis cases evaluated and treated by our
      department, covering both Level I and Level II Trauma Centers, were reviewed for
      total charges, length of hospital stay, length of intensive care unit (ICU) stay,
      and number of procedures. The admission Acute Physiology and Chronic Health
      Evaluation II score was calculated for each patient. Three comparative index
      cases of upper extremity necrotizing fasciitis managed primarily by the plastic
      surgery team are presented in greater detail. RESULTS: Patients managed primarily
      by the plastic surgery service had equivalent Acute Physiology and Chronic Health
      Evaluation II scores to patients managed by multiple services for their
      necrotizing fasciitis, with the average score higher for patients managed by
      plastic surgery alone. In a case-matched series of upper extremity necrotizing
      fasciitis, the patients admitted directly to plastic surgery had shorter average
      lengths of hospital and ICU stays as well as decreased total number of
      procedures, resulting in decreased average total hospital charges. There were no
      amputations among the cases treated primarily by the plastic surgery. The
      patients also required smaller areas of reconstruction with skin grafting despite
      large initial areas of debridement compared to those whose reconstructive teams
      differed from the team performing the debridement. CONCLUSIONS: Improved economic
      and clinical outcomes-as indicated by the reduced lengths of overall and ICU
      stay, the reduced number of procedures, none of the cases requiring amputation,
      and the reduced need for skin grafting-may be attainable when the surgeon
      eventually performing the reconstruction is involved early in management. We
      propose that, in the interest of improving patient care, a closer collaboration
      should be established between the reconstructive and primary managing teams.

PMID- 24740022
TI  - Rigid fixation for the prevention and treatment of sternal complications.
AB  - BACKGROUND: Most surgical specialties working with bone have transitioned from
      wire fixation to more stable plate and screw fixation. Rigid plate fixation
      results in more rapid bony healing with decreased rates of nonunion, malunion,
      and infection. Despite sternotomies being the most frequently performed
      osteotomy, cerclage wire fixation remains the standard technique of closure. This
      study reviews our 5-year experience with rigid fixation at the University of
      California Davis Medical Center. MATERIALS AND METHODS: A retrospective review of
      patients who underwent rigid sternal fixation between January 2006 and December
      2012 at UC Davis Medical Center was performed. Demographic factors, indications
      for surgery, and risk factors for postoperative complications including
      mediastinitis and nonunion were reviewed. The type of fixation system was
      recorded. Outcomes assessed included dehiscence, deep and superficial infections,
      sternal instability, and need for reoperation. RESULTS: Fifty-seven rigid sternal
      fixations were performed (M/F, 37:20; average age, 54 years; range, 16-79 years).
      Indications for operation included prophylaxis against mediastinitis (61.4%),
      sternal nonunion (24.6%), sternal fractures (7.0%), and pectus deformities
      (7.0%). Of the rigid fixation systems used, 87.3% used SternaLock, 12.7% used
      Talon, 1.8% Lactosorb, and 1.8% Flexigrip. Thirty-five patients were plated for
      prophylaxis against mediastinitis. In the prophylactic group, the average number
      of risk factors per patient was 3.92, indicating very high-risk patients.
      Fourteen patients were plated for sternal nonunion. The average number of risk
      factors in the nonunion group was 1.57. Other less common indications for rigid
      sternal stabilization included sternal fracture (4 patients) and pectus deformity
      (4 patients). Eight patients had a pectoralis flaps performed at the time of
      their sternal fixation, 7 for soft tissue coverage of plates and 1 for coverage
      of a contaminated wound bed. All patients went on to heal their sternums without
      evidence of mediastinitis. CONCLUSIONS: Rigid sternal fixation is a natural
      extension of principles learned from bone stabilization in other parts of the
      body. It can be used for rigid bony fixation of osteotomies performed after
      median sternotomy as well as in sternal reconstructions for traumatic fractures,
      nonunions, and pectus deformities. Rigid sternal fixation can be used safely and
      effectively in the prophylaxis against the development of mediastinitis in
      addition to the treatment of sternal nonunion or malunion in high-risk patients.

PMID- 24740023
TI  - From battleside to stateside: the reconstructive journey of our wounded warriors.
AB  - Recent military operations in Iraq (Operation Iraqi Freedom) and Afghanistan
      (Operation Enduring Freedom) have led to further refinements of the military
      medical system's ability to provide advanced surgical care. The deployment of a
      global trauma care system has directly contributed to improved combat casualty
      survival rates. As a consequence of improved survivorship, a high-volume patient
      population of individuals having challenging multiple extremity
      injuries/amputations has presented to military treatment facilities. These
      patients present with unique mixed pattern blast injuries. Blast injuries
      incorporate multiple mechanisms of injury including penetrating fragmentary
      injury, blunt force trauma, flash burn, and overpressure wave damage. These
      complex injuries have furthered refinements in traditional reconstruction and
      facilitated early application of regenerative medicine therapies. This article
      summarizes information presented at the inaugural Garry Brody, MD Family Invited
      Lectureship presented at the 63rd California Society of Plastic Surgeons Annual. 

PMID- 24740024
TI  - Outcomes of breast reconstruction in breast cancer patients with a history of
      mantle radiation for Hodgkin lymphoma.
AB  - BACKGROUND: Although mantle radiation (ie, extended field radiation) represented
      the standard of care in the past for Hodgkin disease, contemporary treatment of
      lymphoma consists of a multimodal approach with chemotherapy. Patients who were
      exposed to mantle radiation have a higher risk of breast cancer and are more
      susceptible to postoperative complications after breast reconstruction due to
      radiation. In this study, we present postoperative outcomes in patients with a
      history of mantle radiation who underwent mastectomy and breast reconstruction.
      METHODS: All patients at Stanford University Medical Center between January 2006
      and December 2012 with a history of Hodgkin lymphoma treated with mantle
      radiation who received breast reconstruction were identified. A retrospective
      chart review was conducted analyzing patient demographics, history of Hodgkin
      treatment, type of reconstruction, follow-up, and complications. Complications
      were further classified into medical complications, donor-site complications, and
      recipient-site complications. RESULTS: Sixteen patients with a history of Hodgkin
      disease and mantle radiation received breast reconstruction. The average age of
      the patients at their mastectomy was 46 (33-60) years, with the average age at
      the time of their mantle radiation of 20.5 (10-33) years with an average interval
      of radiation to breast cancer treatment of 24.8 (16-38) years. There were five
      unilateral and 11 bilateral reconstructions. All patients had immediate
      reconstruction with tissue expanders (14 patients) or autologous tissue (one
      muscle-sparing transverse rectus abdominis myocutaneous and one transverse upper
      gracilis flap). Eleven (69%) patients had postoperative complications. In the
      patients who had tissue expander reconstruction, there was an overall
      complication rate of 64%, which included capsular contracture (n=5, 56%),
      mastectomy flap necrosis (n=5, 56%), cellulitis (n=4, 44%), seroma (n=3, 33%),
      hematoma (n=1, 11%), and chronic pain (n=1, 11%). Three (two unilateral and one
      bilateral) tissue expander infections required removal of the expander and
      delayed reconstruction with a latissimus dorsi flap, whereas one patient with
      chronic pain and capsular contracture required a muscle-sparing transverse rectus
      abdominis myocutaneous for a unilateral implant failure. CONCLUSIONS: Although
      the risk of complications associated with preoperative radiation is well
      documented, physicians and patients should be cognizant of the increased risk of
      complications after mantle radiation as it represents a unique modality of
      radiation exposure.

PMID- 24740025
TI  - AeroForm patient controlled tissue expansion and saline tissue expansion for
      breast reconstruction: a randomized controlled trial.
AB  - BACKGROUND: Prosthetic reconstruction of the breast, as a 2-staged procedure
      using tissue expanders followed by placement of permanent implants, offers
      favorable aesthetic results with minimal additional surgical intervention.
      However, the current outpatient process to fill saline expanders can be lengthy
      and onerous, involving months of office visits and discomfort from the bolus
      saline expansions. We present a new technology (AeroForm Tissue Expansion
      System), which has the potential to improve the process of breast tissue
      expansion by providing a method for low-volume incremental filling, eliminating
      the need for injections and directly involving the patient by allowing her some
      control over the expansion process. METHODS: The described study is a 2:1
      randomized controlled trial of the investigational CO2 expansion system and
      saline expanders. Of the 82 women receiving expanders, 58 (39 bilateral and 19
      unilateral; bilateral rate, 67%) were implanted with CO2 tissue expanders and 24
      subjects (15 bilateral and 9 unilateral; bilateral rate, 63%) were implanted with
      saline expanders. RESULTS: Preliminary validated expansion results were available
      for 55 women. Available mean time for active expansion in the CO2 group was 18.2
      (9.2) days (median, 14.0; range, 5-39; number of expanders, 53), which was less
      than the mean time for active expansion in the saline group: 57.4 (33.6) days
      (median, 55; range, 5-137; number of expanders, 33). Available mean time from
      implant placement to exchange for a permanent prosthesis in the CO2 group was
      shorter [106.3 (42.9) days; median, 99; range, 42-237; number of expanders, 53]
      than for the women in the control group [151.7 (62.6) days; median, 140; range,
      69-433; number of expanders, 33]. After 2 events--underexpansion (n=1) and
      erosion (n=1)--in the CO2 group, the internal membrane was redesigned and the
      expander bulk was decreased to minimize the risk of underexpansion and erosion in
      subsequent patients. CONCLUSIONS: Preliminary evidence indicates that the CO2
      based tissue expansion system performs the same function as saline expansion
      devices without significantly altering the risk to the patient and that the
      device has the potential to make the expansion process faster and more convenient
      for both the patient and the physician.

PMID- 24740027
TI  - An economical training model to teach and practice deep inferior epigastric
      artery perforator dissection.
AB  - INTRODUCTION: Modern surgical training has placed a larger focus on procedural
      competency base training for surgical specialties. Although various simulators
      are in existence to teach laparoscopic skills, plastic surgery has a paucity of
      surgical training models. METHODS AND MATERIALS: We developed a low-cost teaching
      model for the steps and techniques required in the deep inferior epigastric
      perforator flap and assessed the utility of this model with the resident surgeons
      using presurvey and postsurvey. RESULTS: A total of 13 residents participated in
      the surgical skill exercise. The residents felt this exercise increased their
      proficiency in the steps and techniques required for a deep inferior epigastric
      perforator flap harvest [4 (0.4)]. CONCLUSIONS: Overall, residents felt this
      exercise should be included in the postgraduate years 1 and 2 educational
      curriculum.

PMID- 24740026
TI  - Changing attitudes toward hand allotransplantation among North American hand
      surgeons.
AB  - OBJECTIVES: Although more than 70 hand transplants have been performed worldwide,
      the appropriate clinical indications for this operation are still being
      determined. Cost and patient exposure to the challenges of lifelong
      immunosuppression for what is a quality of life-improving (but not life-saving)
      operation are the focus of the ongoing discussion. A study performed in 2007
      showed that surgeons' opinions on the issue varied widely. Recently, more
      information has been made available regarding long-term patient outcomes, and
      significant improvements in immunotherapy protocols have been reported. In light
      of this, we sought to examine changing attitudes regarding hand
      allotransplantation and its indications by surveying hand surgeons. METHODS: An
      email-based survey was sent to members of the American Society for Surgery of the
      Hand. Demographic information and practice profiles were identified, followed by
      their risk assessment of hand allotransplants and endorsement of performing the
      operation in different clinical scenarios. Additional questions focused on the
      appropriate indications for hand allotransplantation, as well as the procedure's
      associated ethical and financial implications. RESULTS: A total of 385 surgeons
      responded to the survey (14% response rate). The majority (82%) considered hand
      transplantation to be a high-risk operation (as opposed to 27% in hand
      replantation), with 78% citing lifelong immunosuppression as the primary factor
      impacting their overall risk assessment. The most commonly accepted indication
      for hand vascularized composite allotransplantation was loss of bilateral hands
      (80% in favor). Dominant hand loss (with an intact contralateral hand) was a far
      less frequently accepted indication (36% in favor). Patient adherence to
      immunosuppressive regimens (51%) and expectations of functional/aesthetic outcome
      (38%) were the most frequently chosen top psychosocial issues that must be
      addressed by the surgical/medical teams involved in the operation. CONCLUSIONS:
      Our study's results demonstrate increasing overall support for hand
      allotransplantation and increasing acceptance of today's immunosuppressive
      regimens compared to prior literature. Bilateral hand loss remains the primary
      agreed-upon indication for transplantation. Despite increasing acceptance in the
      surgical community, the dangers of chronic immunosuppression, cost and patient
      adherence continue to be the primary concerns hindering its broader acceptance.

PMID- 24740028
TI  - Statewide multicenter analysis of the incidence of secondary surgeries after
      isolated cleft palate repair.
AB  - INTRODUCTION: Previous smaller studies have reported a wide range, 15% to 45%, of
      secondary palate surgery. The goal of this study was to report the true incidence
      of secondary surgery derived from a large statewide database as well as study the
      timing and risk factors for secondary surgery. METHODS: Retrospective
      longitudinal analysis was performed of the 1995 to 2010 California Office of
      Statewide Health Planning and Development patient discharge database, which
      allows patients to be followed up over time. Patients were included in the study
      if they had an isolated palate diagnosis in addition to a primary repair code and
      excluded if they ever carried a cleft lip diagnosis or repair code. RESULTS: A
      total of 2616 isolated cleft palate patients were identified with a median follow
      up of 8.0 years. At 16 years, the overall rate of second surgery was 13.6% with
      complete cleft palate patients having a higher rate of second surgery (15.92%)
      than the incomplete cleft palate patients (12.36%). The risk of second surgery
      over time showed a bimodal distribution; the first peak was seen in the first
      postoperative year and the second peak was seen 3 to 5 years postoperative. On
      multivariate regression, the only independent risk factor of a secondary surgery
      was uninsured status (HR, 4.55 [1.64-12.64]), whereas incomplete cleft palate
      (HR, 0.68 [0.46-0.98]) and Hispanic ethnicity (HR, 0.68 [0.50-0.94]) were found
      to be protective for secondary surgery with the rest of the covariates not
      showing significant association. CONCLUSIONS: The incidence rate of secondary
      surgery (13.6%) at 16 years was less than reported in the literature. Patients
      who had a complete cleft palate repaired showed a higher incidence rate compared
      with those who had an incomplete cleft repaired, likely correlating with the
      complexity and invasiveness of the primary surgery. The first risk peak at which
      secondary surgeries were performed reflects the short-term complications that
      needed to be addressed within the first postoperative year. The second peak
      reflects the longer-term complications diagnosed at the age at which children
      reach speech milestones.

PMID- 24740029
TI  - An investigation of outpatient children's blood lead level in Wuhan China.
AB  - OBJECTIVE: Blood lead levels (BLLs) and possible influencing factors in children
      in Wuhan China were investigated in order to understand current lead pollution
      exposure and provide a scientific basis for prevention and policy making.
      MATERIALS AND METHODS: BLL data were collected from 15,536 out-patients in Wuhan
      Children Hospital in 2012 full year. All of them were under 18 years of age (Mean
      +/- SD: 4.32 +/- 3.2, 64.4% boys). The BLLs were measured by an atomic absorption
      spectrometry (BH2100). RESULTS: The geometric mean of BLLs for all the subjects
      was 44.75 ug/L (95%CI: 44.46 ug/L - 45.05 ug/L), much lower than that reported in
      previous studies. The prevalence of the elevated BLLs (>= 100 ug/L) in the
      children tested was 2% in 2012 and the prevalence of BLLs (>= 50 ug/L) was 44%.
      Age and sex could be possible influencing factors for BLLs in the children
      (p<0.001). In addition, the BLLs in different seasons were different (p<0.001).
      CONCLUSIONS: These results demonstrate that BLLs have significantly decreased in
      children in Wuhan during recent years. However, we should continuously pay
      attention to lead pollution and emphasize that prevention is much more important
      than treatment for controlling children's BLLs.

PMID- 24740030
TI  - Beware of backroom deals in the name of 'science'.

PMID- 24740042
TI  - Hepatitis C drugs not reaching poor.

PMID- 24740043
TI  - Sperm RNA carries marks of trauma.

PMID- 24740044
TI  - Panel homes in on sites for gamma-ray detector.

PMID- 24740045
TI  - IPCC report under fire.

PMID- 24740011
TI  - Assessment of the worldwide burden of critical illness: the intensive care over
      nations (ICON) audit.
AB  - BACKGROUND: Global epidemiological data regarding outcomes for patients in
      intensive care units (ICUs) are scarce, but are important in understanding the
      worldwide burden of critical illness. We, therefore, did an international audit
      of ICU patients worldwide and assessed variations between hospitals and countries
      in terms of ICU mortality. METHODS: 730 participating centres in 84 countries
      prospectively collected data on all adult (>16 years) patients admitted to their
      ICU between May 8 and May 18, 2012, except those admitted for fewer than 24 h for
      routine postoperative monitoring. Participation was voluntary. Data were
      collected daily for a maximum of 28 days in the ICU and patients were followed up
      for outcome data until death or hospital discharge. In-hospital death was
      analysed using multilevel logistic regression with three levels: patient,
      hospital, and country. FINDINGS: 10,069 patients were included from ICUs in
      Europe (5445 patients; 54.1%), Asia (1928; 19.2%), the Americas (1723; 17.1%),
      Oceania (439; 4.4%), the Middle East (393; 3.9%), and Africa (141; 1.4%).
      Overall, 2973 patients (29.5%) had sepsis on admission or during the ICU stay.
      ICU mortality rates were 16.2% (95% CI 15.5-16.9) across the whole population and
      25.8% (24.2-27.4) in patients with sepsis. Hospital mortality rates were 22.4%
      (21.6-23.2) in the whole population and 35.3% (33.5-37.1) in patients with
      sepsis. Using a multilevel analysis, the unconditional model suggested
      significant between-country variations (var=0.19, p=0.002) and between-hospital
      variations (var=0.43, p<0.0001) in the individual risk of in-hospital death.
      There was a stepwise increase in the adjusted risk of in-hospital death according
      to decrease in global national income. INTERPRETATION: This large database
      highlights that sepsis remains a major health problem worldwide, associated with
      high mortality rates in all countries. Our findings also show a significant
      association between the risk of death and the global national income and suggest
      that ICU organisation has an important effect on risk of death. FUNDING: None.

PMID- 24740046
TI  - Biologist defiant over stem-cell method.

PMID- 24740047
TI  - Mini satellites prove their scientific power.

PMID- 24740049
TI  - Power from the oceans: Blue energy.

PMID- 24740050
TI  - Toxicology: The plastics puzzle.

PMID- 24740055
TI  - Rechargeables: Vanadium batteries will be cost-effective.

PMID- 24740056
TI  - Laboratory training: Experimentation is science's lifeblood.

PMID- 24740057
TI  - Animal models: Mouse already being charted gene by gene.

PMID- 24740058
TI  - Reproducibility: A trading scheme to reduce false results.

PMID- 24740059
TI  - Energy: China leads the way on renewables.

PMID- 24740060
TI  - Evolutionary biology: Dating chimpanzees.

PMID- 24740061
TI  - Genetics: Up and down in Down's syndrome.

PMID- 24740062
TI  - Thermoelectricity: The ugly duckling.

PMID- 24740064
TI  - The ensemble nature of allostery.
AB  - Allostery is the process by which biological macromolecules (mostly proteins)
      transmit the effect of binding at one site to another, often distal, functional
      site, allowing for regulation of activity. Recent experimental observations
      demonstrating that allostery can be facilitated by dynamic and intrinsically
      disordered proteins have resulted in a new paradigm for understanding allosteric
      mechanisms, which focuses on the conformational ensemble and the statistical
      nature of the interactions responsible for the transmission of information.
      Analysis of allosteric ensembles reveals a rich spectrum of regulatory
      strategies, as well as a framework to unify the description of allosteric
      mechanisms from different systems. 

PMID- 24740066
TI  - Isotopic links between atmospheric chemistry and the deep sulphur cycle on Mars.
AB  - The geochemistry of Martian meteorites provides a wealth of information about the
      solid planet and the surface and atmospheric processes that occurred on Mars. The
      degree to which Martian magmas may have assimilated crustal material, thus
      altering the geochemical signatures acquired from their mantle sources, is
      unclear. This issue features prominently in efforts to understand whether the
      source of light rare-earth elements in enriched shergottites lies in crustal
      material incorporated into melts or in mixing between enriched and depleted
      mantle reservoirs. Sulphur isotope systematics offer insight into some aspects of
      crustal assimilation. The presence of igneous sulphides in Martian meteorites
      with sulphur isotope signatures indicative of mass-independent fractionation
      suggests the assimilation of sulphur both during passage of magmas through the
      crust of Mars and at sites of emplacement. Here we report isotopic analyses of 40
      Martian meteorites that represent more than half of the distinct known Martian
      meteorites, including 30 shergottites (28 plus 2 pairs, where pairs are separate
      fragments of a single meteorite), 8 nakhlites (5 plus 3 pairs), Allan Hills 84001
      and Chassigny. Our data provide strong evidence that assimilation of sulphur into
      Martian magmas was a common occurrence throughout much of the planet's history.
      The signature of mass-independent fractionation observed also indicates that the
      atmospheric imprint of photochemical processing preserved in Martian meteoritic
      sulphide and sulphate is distinct from that observed in terrestrial analogues,
      suggesting fundamental differences between the dominant sulphur chemistry in the
      atmosphere of Mars and that in the atmosphere of Earth. 

PMID- 24740065
TI  - Domains of genome-wide gene expression dysregulation in Down's syndrome.
AB  - Trisomy 21 is the most frequent genetic cause of cognitive impairment. To assess
      the perturbations of gene expression in trisomy 21, and to eliminate the noise of
      genomic variability, we studied the transcriptome of fetal fibroblasts from a
      pair of monozygotic twins discordant for trisomy 21. Here we show that the
      differential expression between the twins is organized in domains along all
      chromosomes that are either upregulated or downregulated. These gene expression
      dysregulation domains (GEDDs) can be defined by the expression level of their
      gene content, and are well conserved in induced pluripotent stem cells derived
      from the twins' fibroblasts. Comparison of the transcriptome of the Ts65Dn mouse
      model of Down's syndrome and normal littermate mouse fibroblasts also showed
      GEDDs along the mouse chromosomes that were syntenic in human. The GEDDs
      correlate with the lamina-associated (LADs) and replication domains of mammalian
      cells. The overall position of LADs was not altered in trisomic cells; however,
      the H3K4me3 profile of the trisomic fibroblasts was modified and accurately
      followed the GEDD pattern. These results indicate that the nuclear compartments
      of trisomic cells undergo modifications of the chromatin environment influencing
      the overall transcriptome, and that GEDDs may therefore contribute to some
      trisomy 21 phenotypes. 

PMID- 24740067
TI  - Coherent suppression of electromagnetic dissipation due to superconducting
      quasiparticles.
AB  - Owing to the low-loss propagation of electromagnetic signals in superconductors,
      Josephson junctions constitute ideal building blocks for quantum memories,
      amplifiers, detectors and high-speed processing units, operating over a wide band
      of microwave frequencies. Nevertheless, although transport in superconducting
      wires is perfectly lossless for direct current, transport of radio-frequency
      signals can be dissipative in the presence of quasiparticle excitations above the
      superconducting gap. Moreover, the exact mechanism of this dissipation in
      Josephson junctions has never been fully resolved experimentally. In particular,
      Josephson's key theoretical prediction that quasiparticle dissipation should
      vanish in transport through a junction when the phase difference across the
      junction is pi (ref. 2) has never been observed. This subtle effect can be
      understood as resulting from the destructive interference of two separate
      dissipative channels involving electron-like and hole-like quasiparticles. Here
      we report the experimental observation of this quantum coherent suppression of
      quasiparticle dissipation across a Josephson junction. As the average phase bias
      across the junction is swept through pi, we measure an increase of more than one
      order of magnitude in the energy relaxation time of a superconducting artificial
      atom. This striking suppression of dissipation, despite the presence of lossy
      quasiparticle excitations above the superconducting gap, provides a powerful tool
      for minimizing decoherence in quantum electronic systems and could be directly
      exploited in quantum information experiments with superconducting quantum bits. 

PMID- 24740068
TI  - Ultralow thermal conductivity and high thermoelectric figure of merit in SnSe
      crystals.
AB  - The thermoelectric effect enables direct and reversible conversion between
      thermal and electrical energy, and provides a viable route for power generation
      from waste heat. The efficiency of thermoelectric materials is dictated by the
      dimensionless figure of merit, ZT (where Z is the figure of merit and T is
      absolute temperature), which governs the Carnot efficiency for heat conversion.
      Enhancements above the generally high threshold value of 2.5 have important
      implications for commercial deployment, especially for compounds free of Pb and
      Te. Here we report an unprecedented ZT of 2.6 +/- 0.3 at 923 K, realized in SnSe
      single crystals measured along the b axis of the room-temperature orthorhombic
      unit cell. This material also shows a high ZT of 2.3 +/- 0.3 along the c axis but
      a significantly reduced ZT of 0.8 +/- 0.2 along the a axis. We attribute the
      remarkably high ZT along the b axis to the intrinsically ultralow lattice thermal
      conductivity in SnSe. The layered structure of SnSe derives from a distorted rock
      salt structure, and features anomalously high Gruneisen parameters, which reflect
      the anharmonic and anisotropic bonding. We attribute the exceptionally low
      lattice thermal conductivity (0.23 +/- 0.03 W m(-1) K(-1) at 973 K) in SnSe to
      the anharmonicity. These findings highlight alternative strategies to
      nanostructuring for achieving high thermoelectric performance. 

PMID- 24740073
TI  - A quality control program within a clinical trial Consortium for PCR protocols to
      detect Plasmodium species.
AB  - Malaria parasite infections that are only detectable by molecular methods are
      highly prevalent and represent a potential transmission reservoir. The methods
      used to detect these infections are not standardized, and their operating
      characteristics are often unknown. We designed a proficiency panel of Plasmodium
      spp. in order to compare the accuracy of parasite detection of molecular
      protocols used by labs in a clinical trial consortium. Ten dried blood spots
      (DBSs) were assembled that contained P. falciparum, P. vivax, P. malariae, and P.
      ovale; DBSs contained either a single species or a species mixed with P.
      falciparum. DBS panels were tested in 9 participating laboratories in a masked
      fashion. Of 90 tests, 68 (75.6%) were correct; there were 20 false-negative
      results and 2 false positives. The detection rate was 77.8% (49/63) for P.
      falciparum, 91.7% (11/12) for P. vivax, 83.3% (10/12) for P. malariae, and 70%
      (7/10) for P. ovale. Most false-negative P. falciparum results were from samples
      with an estimated <= 5 parasites per MUl of blood. Between labs, accuracy ranged
      from 100% to 50%. In one lab, the inability to detect species in mixed-species
      infections prompted a redesign and improvement of the assay. Most PCR-based
      protocols were able to detect P. falciparum and P. vivax at higher densities, but
      these assays may not reliably detect parasites in samples with low P. falciparum
      densities. Accordingly, formal quality assurance for PCR should be employed
      whenever this method is used for diagnosis or surveillance. Such efforts will be
      important if PCR is to be widely employed to assist malaria elimination efforts.

PMID- 24740074
TI  - Profiling of rpoB mutations and MICs for rifampin and rifabutin in Mycobacterium
      tuberculosis.
AB  - Resistance to rifampin (RIF) and rifabutin (RFB) in Mycobacterium tuberculosis is
      associated with mutations within an 81-bp region of the rpoB gene (RIF resistance
      determining region [RRDR]). Previous studies have shown that certain mutations in
      this region are more likely to confer high levels of RIF resistance, while others
      may be found in phenotypically susceptible isolates. In this study, we sought to
      determine the relationship between the MICs of RIF and RFB and rpoB RRDR
      mutations in 32 multidrug-resistant (MDR), 4 RIF-monoresistant, and 5 susceptible
      M. tuberculosis clinical isolates. The MICs were determined using the MGIT 960
      system. Mutations in the rpoB RRDR were determined by Sanger sequencing. RpoB
      proteins with mutations S531L (a change of S to L at position 531), S531W, H526Y,
      and H526D and the double mutation D516A-R529Q were associated with high MICs for
      RIF and RFB. Five isolates carrying the mutations L511P, H526L, H526N, and D516G
      S522L were found to be susceptible to RIF. Several mutations were associated with
      resistance to RIF and susceptibility to RFB (F514FF, D516V, and S522L). Whole
      genome sequencing of two MDR isolates without rpoB RRDR mutations revealed a
      mutation outside the RRDR (V146F; RIF MIC of 50 MUg/ml). The implications of the
      polymorphisms identified in the second of these isolates in RIF resistance need
      to be further explored. Our study further establishes a correlation between the
      mutations and the MICs of RIF and, also, RFB in M. tuberculosis. Several rpoB
      mutations were identified in RIF- and RFB-susceptible isolates. The clinical
      significance of these findings requires further exploration. Until then, a
      combination of phenotypic and molecular testing is advisable for drug
      susceptibility testing. 

PMID- 24740075
TI  - First report of Mycobacterium canariasense catheter-related bacteremia in the
      Americas.
AB  - Mycobacterium canariasense is a recently described late-pigmenting, rapidly
      growing mycobacterium linked to bacteremia in patients with underlying malignant
      diseases. We report a case of M. canariasense infection in a patient from
      Massachusetts with underlying diffuse B cell lymphoma, which was identified both
      by multilocus sequence typing and matrix-assisted laser desorption ionization
      time of flight mass spectrometry (MALDI-TOF MS). To our knowledge, this is the
      first description after its original identification in Spain and the first report
      of this opportunistic pathogen in the Americas. 

PMID- 24740076
TI  - Detection of Neisseria meningitidis from negative blood cultures and
      cerebrospinal fluid with the FilmArray blood culture identification panel.
AB  - The FilmArray blood culture identification (BCID) panel is a rapid molecular
      diagnostic test approved for use with positive blood culture material. We
      describe a fatal case of meningococcemia with central nervous system (CNS)
      involvement detected using the BCID test with culture-negative blood and
      cerebrospinal fluid. 

PMID- 24740077
TI  - Determining the optimal ceftriaxone MIC for triggering extended-spectrum beta
      lactamase confirmatory testing.
AB  - As routine testing of clinical isolates for extended-spectrum beta-lactamase
      (ESBL) production (screen plus phenotypic confirmatory testing) is no longer
      required by the Clinical and Laboratory Standards Institute (CLSI), a number of
      clinical microbiology laboratories use ceftriaxone MICs as a proxy means of
      identifying bacteria as potential ESBL producers. Data from 1,386 clinical
      isolates suggest that a ceftriaxone MIC cutoff of 8 MUg/ml is an excellent
      predictor of ESBL production, with a positive predictive value and negative
      predictive value approaching 100% and 99.5%, respectively. 

PMID- 24740078
TI  - Inhibition controls for qualitative real-time PCR assays: are they necessary for
      all specimen matrices?
AB  - A retrospective analysis of 386,706 specimens representing a variety of matrix
      types used in qualitative real-time PCR assays determined the overall inhibition
      rate to be 0.87% when the inhibition control was added preextraction to 5,613
      specimens and 0.01% when the inhibition control was added postextraction but
      preamplification in 381,093 specimens. Inhibition rates of <= 1% were found for
      all specimen matrix types except urine and formalin-fixed, paraffin-embedded
      tissue.

PMID- 24740079
TI  - Comparison of real-time PCR and antigen assays for detection of hepatitis E virus
      in blood donors.
AB  - Hepatitis E virus (HEV) infection is recognized as an emerging and often
      undiagnosed disease in industrialized countries, with asymptomatic infections
      actually occurring in blood donors. Sensitive detection of HEV-RNA is crucial for
      diagnosis and monitoring of disease progression. We evaluated the analytical
      sensitivity and performance of three HEV RT-PCR assays (RealStar HEV reverse
      transcription-PCR [RT-PCR], hepatitis@ceeramTools, and ampliCube HEV RT-PCR) for
      screening of individuals for HEV infections (ID-nucleic acid amplification
      technology [ID-NAT]) and for blood donor pool screening (minipool-NAT [MP-NAT]).
      RNA was extracted using NucliSens easyMAG (ID-NAT) and a high-volume extraction
      protocol (4.8 ml, chemagic Viral 5K, MP-NAT). Three NAT assays were evaluated for
      ID-NAT but only two assays for MP-NAT due to inhibition of the ampliCube HEV RT
      PCR kit using the corresponding RNA extract. Assays provided good analytical
      sensitivity, ranging from 37.8 to 180.1 IU/ml (ID-NAT) and from 4.7 to 91.2 IU/ml
      (MP-NAT). The applicability of HEV antigen (HEV-Ag) screening was compared to
      that of RT-PCR screening and detection of HEV-IgM antibodies using seroconversion
      panels of 10 HEV genotype 3-infected individuals. Four individuals revealed a
      positive HEV-Ag detection result, with corresponding viremias ranging from 1.92 E
      + 03 to 2.19 E + 05 IU/ml, while the progression of HEV-Ag followed that of HEV
      viremia. The other six individuals showed no presence of HEV-Ag although the
      corresponding viremias were also in the range of >1.0 E + 03. Anti-HEV-IgM
      antibodies were detectable in seven donors; one donor presented parallel
      positivities of HEV-Ag and anti-HEV IgM. The evaluated NAT methods present
      powerful tools providing sensitive HEV detection. Application of HEV-Ag or anti
      HEV IgM screening is currently inferior for the early detection of HEV infection
      due to the decreased sensitivity compared to NAT methods.

PMID- 24740080
TI  - Validation of an oligonucleotide ligation assay for quantification of human
      immunodeficiency virus type 1 drug-resistant mutants by use of massively parallel
      sequencing.
AB  - Global HIV treatment programs need sensitive and affordable tests to monitor HIV
      drug resistance. We compared mutant detection by the oligonucleotide ligation
      assay (OLA), an economical and simple test, to massively parallel sequencing.
      Nonnucleoside reverse transcriptase inhibitor (K103N, V106M, Y181C, and G190A)
      and lamivudine (M184V) resistance mutations were quantified in blood-derived
      plasma RNA and cell DNA specimens by OLA and 454 pyrosequencing. A median of
      1,000 HIV DNA or RNA templates (range, 163 to 1,874 templates) from blood
      specimens collected in Mozambique (n = 60) and Kenya (n = 51) were analyzed at 4
      codons in each sample (n = 441 codons assessed). Mutations were detected at 75
      (17%) codons by OLA sensitive to 2.0%, at 71 codons (16%; P = 0.78) by
      pyrosequencing using a cutoff value of >= 2.0%, and at 125 codons (28%; P <
      0.0001) by pyrosequencing sensitive to 0.1%. Discrepancies between the assays
      included 15 codons with mutant concentrations of ~2%, one at 8.8% by
      pyrosequencing and not detected by OLA, and one at 69% by OLA and not detected by
      pyrosequencing. The latter two cases were associated with genetic polymorphisms
      in the regions critical for ligation of the OLA probes and pyrosequencing
      primers, respectively. Overall, mutant concentrations quantified by the two
      methods correlated well across the codons tested (R(2) > 0.8). Repeat
      pyrosequencing of 13 specimens showed reproducible detection of 5/24 mutations at
      <2% and 6/6 at >= 2%. In conclusion, the OLA and pyrosequencing performed
      similarly in the quantification of nonnucleoside reverse transcriptase inhibitor
      and lamivudine mutations present at >2% of the viral population in clinical
      specimens. While pyrosequencing was more sensitive, detection of mutants below 2%
      was not reproducible.

PMID- 24740081
TI  - Workflow and maintenance characteristics of five automated laboratory instruments
      for the diagnosis of sexually transmitted infections.
AB  - The choice of a suitable automated system for a diagnostic laboratory depends on
      various factors. Comparative workflow studies provide quantifiable and objective
      metrics to determine hands-on time during specimen handling and processing,
      reagent preparation, return visits and maintenance, and test turnaround time and
      throughput. Using objective time study techniques, workflow characteristics for
      processing 96 and 192 tests were determined on m2000 RealTime (Abbott Molecular),
      Viper XTR (Becton Dickinson), cobas 4800 (Roche Molecular Diagnostics), Tigris
      (Hologic Gen-Probe), and Panther (Hologic Gen-Probe) platforms using second
      generation assays for Chlamydia trachomatis and Neisseria gonorrhoeae. A
      combination of operational and maintenance steps requiring manual labor showed
      that Panther had the shortest overall hands-on times and Viper XTR the longest.
      Both Panther and Tigris showed greater efficiency whether 96 or 192 tests were
      processed. Viper XTR and Panther had the shortest times to results and m2000
      RealTime the longest. Sample preparation and loading time was the shortest for
      Panther and longest for cobas 4800. Mandatory return visits were required only
      for m2000 RealTime and cobas 4800 when 96 tests were processed, and both required
      substantially more hands-on time than the other systems due to increased numbers
      of return visits when 192 tests were processed. These results show that there are
      substantial differences in the amount of labor required to operate each system.
      Assay performance, instrumentation, testing capacity, workflow, maintenance, and
      reagent costs should be considered in choosing a system. 

PMID- 24740082
TI  - High applicability of a novel method for gp60-based subtyping of Cryptosporidium
      meleagridis.
AB  - Cryptosporidium meleagridis is a common cause of cryptosporidiosis in avian hosts
      and the third most common species involved in human cryptosporidiosis. Sequencing
      of the highly polymorphic 60-kDa glycoprotein (gp60) gene is a frequently used
      tool for investigation of the genetic diversity and transmission dynamics of
      Cryptosporidium. However, few studies have included gp60 sequencing of C.
      meleagridis. One explanation may be that the gp60 primers currently in use are
      based on Cryptosporidium hominis and Cryptosporidium parvum sequence data,
      potentially limiting successful amplification of the C. meleagridis gp60 gene. We
      therefore aimed to design primers for better gp60 subtyping of C. meleagridis.
      Initially, ~1,440 bp of the gp60 locus of seven C. meleagridis isolates were
      amplified using primers flanking the open reading frame. The obtained sequence
      data (~1,250 bp) were used to design primers for a nested PCR targeting C.
      meleagridis. Twenty isolates (16 from human and 4 from poultry) previously
      identified as C. meleagridis by analysis of small subunit (SSU) rRNA genes were
      investigated. Amplicons of the expected size (~900 bp) were obtained from all 20
      isolates. The subsequent sequence analysis identified 3 subtype families and 10
      different subtypes. The most common subtype family, IIIb, was identified in 12
      isolates, represented by 6 subtypes, 4 new and 2 previously reported. Subtype
      family IIIe was found in 3 isolates represented by 3 novel, distinct subtypes.
      Finally, IIIgA31G3R1 was found in 1 human isolate and 4 poultry isolates, all
      originating from a previously reported C. meleagridis outbreak at a Swedish
      organic farm. 

PMID- 24740083
TI  - Comparison of FecalSwab and ESwab devices for storage and transportation of
      Diarrheagenic bacteria.
AB  - Using a collection (n = 12) of ATCC and known stock isolates, as well as 328
      clinical stool specimens, we evaluated the ESwab and the new FecalSwab liquid
      based microbiology (LBM) devices for storing and transporting diarrheagenic
      bacteria. The stock isolates were stored in these swab devices up to 48 h at
      refrigeration (4 degrees C) or room (~25 degrees C) temperature and up to 3
      months at -20 degrees C or -70 degrees C. With the clinical stool specimens, the
      performances of the ESwab and FecalSwab were compared to those of routinely used
      transport systems (Amies gel swabs and dry containers). At a refrigeration
      temperature, all isolates survived in FecalSwab up to 48 h, while in ESwab, only
      10 isolates (83.3%) out of 12 survived. At -70 degrees C, all isolates in
      FecalSwab were recovered after 3 months of storage, whereas in ESwab, none of the
      isolates were recovered. At -20 degrees C, neither of the swab devices preserved
      the viability of stock isolates after 2 weeks of storage, and at room
      temperature, 7 (58.3%) of the stock isolates were recovered in both transport
      devices after 48 h. Of the 328 fecal specimens, 44 (13.4%) were positive for one
      of the common diarrheagenic bacterial species with all transport systems used.
      Thus, the suitability of the ESwab and FecalSwab devices for culturing fresh
      stools was at least equal to those of the Amies gel swabs and dry containers.
      Although the ESwab was shown to be an option for collecting and transporting
      fecal specimens, the FecalSwab device had clearly better preserving properties
      under different storage conditions. 

PMID- 24740084
TI  - Use and limits of (1-3)-beta-d-glucan assay (Fungitell), compared to
      galactomannan determination (Platelia Aspergillus), for diagnosis of invasive
      aspergillosis.
AB  - This study was undertaken to examine the performance of the Fungitell beta-glucan
      (BG) assay, to compare it with that of the galactomannan (GM) test for the
      diagnosis of invasive aspergillosis (IA) in patients with hematological
      malignancies, and to examine the rates of false-positive BG and GM test results
      due to beta-lactam antibiotics among sera of patients with Gram-positive or Gram
      negative bacteremia and selected sera with false-positive results from the GM
      test. Serum samples from 105 patients with proven (n = 14) or probable (n = 91)
      IA, 97 hematology patients at risk for invasive fungal infections, 50 healthy
      blood donors, and 60 patients with bacteremia were used to study the
      sensitivities and specificities of the assays. The GM test was more specific than
      the BG assay (97% versus 82%, respectively; P = 0.0001) and the BG assay was more
      sensitive than the GM test (81% versus 49%, respectively; P < 0.0001) for IA
      diagnosis. The study of 49 separate batches of beta-lactam antibiotics showed
      high and very similar rates of false-positive results for the GM and BG assays
      (29 and 33%, respectively; P = 0.82) but with an almost complete lack of
      concordance between the 2 assays. For patients with bacteremia, the rate of false
      positive results was much higher with the BG test than with the GM test (37%
      versus 2%, respectively; P < 0.0001), with no significant difference between Gram
      positive and Gram-negative bacteremia. In conclusion, the BG test may be useful
      for the diagnosis of IA because of its high sensitivity in comparison with the GM
      test, but the overall benefit of this assay remains limited because of its
      inadequate specificity and its cost. 

PMID- 24740085
TI  - Direct identification of Streptococcus pneumoniae capsular types in pleural
      fluids by using multiplex PCR combined with automated fluorescence-based
      capillary electrophoresis.

PMID- 24740087
TI  - Transformation of HIV from pandemic to low-endemic levels: a public health
      approach to combination prevention.
AB  - Large declines in HIV incidence have been reported since 2001, and scientific
      advances in HIV prevention provide strong hope to reduce incidence further. Now
      is the time to replace the quest for so-called silver bullets with a public
      health approach to combination prevention that understands that risk is not
      evenly distributed and that effective interventions can vary by risk profile.
      Different countries have different microepidemics, with very different levels of
      transmission and risk groups, changing over time. Therefore, focus should be on
      high-transmission geographies, people at highest risk for HIV, and the package of
      interventions that are most likely to have the largest effect in each different
      microepidemic. Building on the backbone of behaviour change, condom use, and
      medical male circumcision, as well as expanded use of antiretroviral drugs for
      infected people and pre-exposure prophylaxis for uninfected people at high risk
      of infection, it is now possible to consider the prospect of what would be one of
      the most remarkable achievements in the history of public health: reduction of
      HIV transmission from a pandemic to low-level endemicity. 

PMID- 24740086
TI  - Prenatal development is linked to bronchial reactivity: epidemiological and
      animal model evidence.
AB  - Chronic cardiorespiratory disease is associated with low birthweight suggesting
      the importance of the developmental environment. Prenatal factors affecting fetal
      growth are believed important, but the underlying mechanisms are unknown. The
      influence of developmental programming on bronchial hyperreactivity is
      investigated in an animal model and evidence for comparable associations is
      sought in humans. Pregnant Wistar rats were fed either control or protein
      restricted diets throughout pregnancy. Bronchoconstrictor responses were recorded
      from offspring bronchial segments. Morphometric analysis of paraffin-embedded
      lung sections was conducted. In a human mother-child cohort ultrasound
      measurements of fetal growth were related to bronchial hyperreactivity, measured
      at age six years using methacholine. Protein-restricted rats' offspring
      demonstrated greater bronchoconstriction than controls. Airway structure was not
      altered. Children with lesser abdominal circumference growth during 11-19 weeks'
      gestation had greater bronchial hyperreactivity than those with more rapid
      abdominal growth. Imbalanced maternal nutrition during pregnancy results in
      offspring bronchial hyperreactivity. Prenatal environmental influences might play
      a comparable role in humans. 

PMID- 24740088
TI  - Detection of the influenza A(H1N1)pdm09 virus carrying the K-15E, P83S and Q293H
      mutations in patients who have undergone bone marrow transplant.
AB  - The 2009 pandemic influenza A(H1N1)pdm09 virus emerged and caused considerable
      morbidity and mortality in the third world, especially in Brazil. Although
      circulating strains of A(H1N1)pdm09 are A/California/04/2009-like (CA-04-like)
      viruses, various studies have suggested that some mutations in the viral
      hemagglutinin (HA) may be associated with enhanced severity and fatality. This
      phenomenon is particularly challenging for immunocompromised individuals, such as
      those who have undergone bone marrow transplant (BMT), because they are more
      likely to display worse clinical outcomes to influenza infection than non
      immunocompromised individuals. We studied the clinical and viral aspects of post
      BMT patients with confirmed A(H1N1)pdm09 diagnosis in the largest cancer hospital
      in Brazil. We found a viral strain with K-15E, P83S and Q293H polymorphisms in
      the HA, which is presumably more virulent, in these individuals. Despite that,
      these patients showed only mild symptoms of infection. Our findings complement
      the discovery of mild cases of infection with the A(H1N1)pdm09 virus with the K
      15E, P83S and Q293H mutations in Brazil and oppose other studies that have linked
      these changes with increased disease severity. These results could be important
      for a better comprehension of the impact of the pandemic influenza in the context
      of BMT. 

PMID- 24740089
TI  - A novel carbonyl reductase with anti-Prelog stereospecificity from Acetobacter
      sp. CCTCC M209061: purification and characterization.
AB  - A novel carbonyl reductase (AcCR) catalyzing the asymmetric reduction of ketones
      to enantiopure alcohols with anti-Prelog stereoselectivity was found in
      Acetobacter sp. CCTCC M209061 and enriched 27.5-fold with an overall yield of
      0.4% by purification. The enzyme showed a homotetrameric structure with an
      apparent molecular mass of 104 kDa and each subunit of 27 kDa. The gene sequence
      of AcCR was cloned and sequenced, and a 762 bp gene fragment was obtained. Either
      NAD(H) or NADP(H) can be used as coenzyme. For the reduction of 4'
      chloroacetophenone, the Km value for NADH was around 25-fold greater than that
      for NADPH (0.66 mM vs 0.026 mM), showing that AcCR preferred NADPH over NADH.
      However, when NADH was used as cofactor, the response of AcCR activity to
      increasing concentration of 4'-chloroacetophenone was clearly sigmoidal with a
      Hill coefficient of 3.1, suggesting that the enzyme might possess four substrate
      binding sites cooperating with each other The Vmax value for NADH-linked
      reduction was higher than that for NADPH-linked reduction (0.21 mM/min vs 0.17
      mM/min). For the oxidation of isopropanol, the similar enzymological properties
      of AcCR were found using NAD+ or NADP+ as cofactor. Furthermore, a broad range of
      ketones such as aryl ketones, alpha-ketoesters and aliphatic ketones could be
      enantioselectively reduced into the corresponding chiral alcohols by this enzyme
      with high activity. 

PMID- 24740090
TI  - Approaches to recording drug allergies in electronic health records: qualitative
      study.
AB  - BACKGROUND: Drug allergy represent an important subset of adverse drug reactions
      that is worthy of attention because many of these reactions are potentially
      preventable with use of computerised decision support systems. This is however
      dependent on the accurate and comprehensive recording of these reactions in the
      electronic health record. The objectives of this study were to understand
      approaches to the recording of drug allergies in electronic health record
      systems. MATERIALS AND METHODS: We undertook a case study comprising of 21 in
      depth interviews with a purposefully selected group of primary and secondary care
      clinicians, academics, and members of the informatics and drug regulatory
      communities, observations in four General Practices and an expert group
      discussion with 15 participants from the Allergy and Respiratory Expert Resource
      Group of the Royal College of General Practitioners. RESULTS: There was
      widespread acceptance among healthcare professionals of the need for accurate
      recording of drug allergies and adverse drug reactions. Most drug reactions were
      however likely to go unreported to and/or unrecognised by healthcare
      professionals and, even when recognised and reported, not all reactions were
      accurately recorded. The process of recording these reactions was not
      standardised. CONCLUSIONS: There is considerable variation in the way drug
      allergies are recorded in electronic health records. This limits the potential of
      computerised decision support systems to help alert clinicians to the risk of
      further reactions. Inaccurate recording of information may in some instances
      introduce new problems as patients are denied treatments that they are
      erroneously believed to be allergic to.

PMID- 24740091
TI  - Wintering habitat model for the North Atlantic Right Whale (Eubalaena glacialis)
      in the southeastern United States.
AB  - The coastal waters off the southeastern United States (SEUS) are a primary
      wintering ground for the endangered North Atlantic right whale (Eubalaena
      glacialis), used by calving females along with other adult and juvenile whales.
      Management actions implemented in this area for the recovery of the right whale
      population rely on accurate habitat characterization and the ability to predict
      whale distribution over time. We developed a temporally dynamic habitat model to
      predict wintering right whale distribution in the SEUS using a generalized
      additive model framework and aerial survey data from 2003/2004 through 2012/2013.
      We built upon previous habitat models for right whales in the SEUS and include
      data from new aerial surveys that extend the spatial coverage of the analysis,
      particularly in the northern portion of this wintering ground. We summarized
      whale sightings, survey effort corrected for probability of whale detection, and
      environmental data at a semimonthly resolution. Consistent with previous studies,
      sea surface temperature (SST), water depth, and survey year were significant
      predictors of right whale relative abundance. Additionally, distance to shore,
      distance to the 22 degrees C SST isotherm, and an interaction between time of
      year and latitude (to account for the latitudinal migration of whales) were also
      selected in the analysis presented here. Predictions from the model revealed that
      the location of preferred habitat differs within and between years in
      correspondence with variation in environmental conditions. Although cow-calf
      pairs were rarely sighted in the company of other whales, there was minimal
      evidence that the preferred habitat of cow-calf pairs was different than that of
      whale groups without calves at the scale of this study. The results of this
      updated habitat model can be used to inform management decisions for a migratory
      species in a dynamic oceanic environment. 

PMID- 24740092
TI  - Comment on: renal impairment and coronary collaterals in patients with acute
      coronary syndrome.

PMID- 24740093
TI  - [Syncope : epidemiology, definition, classification, pathophysiology and
      prognosis].
AB  - Syncope is a common clinical issue. Around 40 % of the total population
      experience syncope during their lifetime. Serious injuries and reduced quality of
      life are often observed after syncope. Furthermore, in some cases syncope can be
      associated with an unfavorable prognosis. Due to the complex etiology and
      pathophysiology, syncope provides challenges for doctors both in private and in
      clinical practices. This review is based on the latest European guidelines for
      syncope which were formulated by internists, neurologists, emergency physicians
      and cardiologists and gives an overview of the current epidemiology, definition,
      classification, pathophysiology and prognosis of syncope.

PMID- 24740095
TI  - [Syncope from the viewpoint of a neurologist].
AB  - Syncope is a pathogenetically diverse syndrome that often requires an
      interdisciplinary investigation. In addition to cardiovascular reasons of syncope
      neurological diseases and differential diagnoses have to be considered. In
      particular, neurodegenerative disorders, such as Parkinson's disease or
      polyneuropathy may cause orthostatic intolerance and syncope due to a malfunction
      of autonomic reflexes. Furthermore, important differential diagnoses of syncope,
      such as epilepsy, drop attacks or circulatory disorders in the territory of the
      basilar artery are attributed to the neurological field. 

PMID- 24740094
TI  - [Percutaneous coronary intervention versus bypass surgery in patients with
      diabetes and multivessel coronary disease. Coronary revascularization after
      FREEDOM].
AB  - Is coronary revascularization required in a patient with chronic stable coronary
      artery disease or can optimized medical therapy (OMT) alone be a sufficient
      alternative? This question has been controversially discussed for non-diabetics
      as well as for diabetics since the COURAGE and BARI 2D trials. According to our
      present knowledge, a patient will benefit from coronary revascularization only
      when either a non-invasive test method, such as single photon emission computed
      tomography (SPECT) or positron emission tomography (PET) myocardial scintigraphy,
      stress echocardiography or stress nuclear magnetic resonance imaging, can detect
      relevant, objective evidence of ischemia >10% of the left ventricular myocardium
      or when a pathological fractional flow reserve (FFR) <0.80 can be measured in an
      invasive procedure for an angiographically detectable coronary stenosis. If
      similar relevant ischemia can be non-invasively or invasively objectified in a
      patient with chronic stable multivessel coronary artery disease, the often
      controversially discussed question arises particularly in diabetics whether a
      percutaneous coronary intervention (PCI) with implantation of drug-eluting stents
      or coronary artery bypass surgery should be favored. The FREEDOM study (Future
      Revascularization Evaluation in Patients with Diabetes Mellitus: Optimal
      Management of Multivessel Disease), published in November 2012, was the first
      prospective randomized study to examine this issue in diabetic patients with
      multivessel coronary artery disease. Despite a higher rate of stroke in the
      surgical cohort, after an average follow-up time of 3.8 years a significant
      prognostic advantage in favor of bypass surgery was detected for a combined
      primary endpoint of all-cause mortality, nonfatal myocardial infarction and
      nonfatal stroke. Thus, in the new ESC guidelines on diabetes, pre-diabetes and
      cardiovascular diseases developed with the EASD of the European Society of
      Cardiology and published in 2013, coronary bypass surgery has a class I, level of
      evidence A recommendation for patients with diabetes mellitus, chronic stable
      multivessel coronary disease and a synergy between PCI with taxus and cardiac
      surgery (SYNTAX) score >22. The decision for or against a PCI/stent implantation
      or coronary bypass surgery in a diabetic patient with chronic stable multivessel
      coronary artery disease should therefore be made with the patient only after a
      detailed informed consent discussion and comprehensive explanation of both
      treatment options. In controversial cases, particularly with an equivocal SYNTAX
      score around 22, relevant comorbidities or anticipated method-specific
      complications, a one-stage ad hoc intervention during the diagnostic coronary
      angiography should be rejected in favor of a two-stage procedure with prior
      discussion of both treatment options in the heart team comprising noninvasive
      cardiologists, interventional cardiologists and cardiac surgeons. 

PMID- 24740096
TI  - A latent class analysis of bullies, victims and aggressive victims in Chinese
      adolescence: relations with social and school adjustments.
AB  - This study used the latent class analysis (LCA) to identify and classify Chinese
      adolescent children's aggressive behaviors. It was found that (1) Adolescent
      children could be divided into four categories: general children, aggressive
      children, victimized children and aggressive victimized children. (2) There were
      significant gender differences among the aggressive victimized children, the
      aggressive children and the general children. Specifically, aggressive victimized
      children and aggressive children had greater probabilities of being boys;
      victimized children had equal probabilities of being boys or girls. (3)
      Significant differences in loneliness, depression, anxiety and academic
      achievement existed among the aggressive victims, the aggressor, the victims and
      the general children, in which the aggressive victims scored the worst in all
      questionnaires. (4) As protective factors, peer and teacher supports had
      important influences on children's aggressive and victimized behaviors. Relative
      to general children, aggressive victims, aggressive children and victimized
      children had lower probabilities of receiving peer supports. On the other hand,
      compared to general children, aggressive victims had lower probabilities of
      receiving teacher supports; while significant differences in the probability of
      receiving teacher supports did not exist between aggressive children and
      victimized children.

PMID- 24740097
TI  - Maturity group classification and maturity locus genotyping of early-maturing
      soybean varieties from high-latitude cold regions.
AB  - BACKGROUND: With the migration of human beings, advances of agricultural
      sciences, evolution of planting patterns and global warming, soybeans have
      expanded to both tropical and high-latitude cold regions (HCRs). Unlike other
      regions, HCRs have much more significant and diverse photoperiods and temperature
      conditions over seasons or across latitudes, and HCR soybeans released there show
      rich diversity in maturity traits. However, HCR soybeans have not been as well
      classified into maturity groups (MGs) as other places. Therefore, it is necessary
      to identify MGs in HCRs and to genotype the maturity loci. METHODS: Local
      varieties were collected from the northern part of Northeast China and the far
      eastern region of Russia. Maturity group reference (MGR) soybeans of MGs MG000,
      MG00, and MG0 were used as references during field experiments. Both local
      varieties and MGR soybeans were planted for two years (2010-2011) in Heihe (N 50
      degrees 15', E 127 degrees 27', H 168.5 m), China. The days to VE (emergence), R1
      (beginning bloom) and R7 (beginning maturity) were recorded and statistically
      analyzed. Furthermore, some varieties were further genotyped at four molecularly
      identified maturity loci E1, E2, E3 and E4. RESULTS: The HCR varieties were
      classified into MG0 or even more early-maturing. In Heihe, some varieties matured
      much earlier than MG000, which is the most early-maturing known MG, and clustered
      into a separate group. We designated the group as MG0000, following the
      convention of MGs. HCR soybeans had relatively stable days to beginning bloom
      from emergence. The HCR varieties diversified into genotypes of E1, E2, E3 and
      E4. These loci had different effects on maturity. CONCLUSION: HCRs diversify
      early-maturing MGs of soybean. MG0000, a new MG that matures much earlier than
      known MGs, was developed. HCR soybean breeding should focus more on shortening
      post-flowering reproductive growth. E1, E2, E3, and E4 function differentially.

PMID- 24740098
TI  - The Kimberley assessment of depression of older Indigenous Australians:
      prevalence of depressive disorders, risk factors and validation of the KICA-dep
      scale.
AB  - OBJECTIVE: This study aimed to develop a culturally acceptable and valid scale to
      assess depressive symptoms in older Indigenous Australians, to determine the
      prevalence of depressive disorders in the older Kimberley community, and to
      investigate the sociodemographic, lifestyle and clinical factors associated with
      depression in this population. METHODS: Cross-sectional survey of adults aged 45
      years or over from six remote Indigenous communities in the Kimberley and 30% of
      those living in Derby, Western Australia. The 11 linguistic and culturally
      sensitive items of the Kimberley Indigenous Cognitive Assessment of Depression
      (KICA-dep) scale were derived from the signs and symptoms required to establish
      the diagnosis of a depressive episode according to the DSM-IV-TR and ICD-10
      criteria, and their frequency was rated on a 4-point scale ranging from 'never'
      to 'all the time' (range of scores: 0 to 33). The diagnosis of depressive
      disorder was established after a face-to-face assessment with a consultant
      psychiatrist. Other measures included sociodemographic and lifestyle factors, and
      clinical history. RESULTS: The study included 250 participants aged 46 to 89
      years (mean+/-SD = 60.9+/-10.7), of whom 143 (57.2%) were women. The internal
      reliability of the KICA-dep was 0.88 and the cut-point 7/8 (non-case/case) was
      associated with 78% sensitivity and 82% specificity for the diagnosis of a
      depressive disorder. The point-prevalence of a depressive disorder in this
      population was 7.7%; 4.0% for men and 10.4% for women. Heart problems were
      associated with increased odds of depression (odds ratio = 3.3, 95% confidence
      interval = 1.2,8.8). CONCLUSIONS: The KICA-dep has robust psychometric properties
      and can be used with confidence as a screening tool for depression among older
      Indigenous Australians. Depressive disorders are common in this population,
      possibly because of increased stressors and health morbidities.

PMID- 24740099
TI  - Serum inflammatory mediators as markers of human Lyme disease activity.
AB  - Chemokines and cytokines are key signaling molecules that orchestrate the
      trafficking of immune cells, direct them to sites of tissue injury and
      inflammation and modulate their states of activation and effector cell function.
      We have measured, using a multiplex-based approach, the levels of 58 immune
      mediators and 7 acute phase markers in sera derived from of a cohort of patients
      diagnosed with acute Lyme disease and matched controls. This analysis identified
      a cytokine signature associated with the early stages of infection and allowed us
      to identify two subsets (mediator-high and mediator-low) of acute Lyme patients
      with distinct cytokine signatures that also differed significantly (p<0.0005) in
      symptom presentation. In particular, the T cell chemokines CXCL9 (MIG), CXCL10
      (IP-10) and CCL19 (MIP3B) were coordinately increased in the mediator-high group
      and levels of these chemokines could be associated with seroconversion status and
      elevated liver function tests (p = 0.027 and p = 0.021 respectively). There was
      also upregulation of acute phase proteins including CRP and serum amyloid A.
      Consistent with the role of CXCL9/CXCL10 in attracting immune cells to the site
      of infection, CXCR3+ CD4 T cells are reduced in the blood of early acute Lyme
      disease (p = 0.01) and the decrease correlates with chemokine levels (p =
      0.0375). The levels of CXCL9/10 did not relate to the size or number of skin
      lesions but elevated levels of serum CXCL9/CXCL10 were associated with elevated
      liver enzymes levels. Collectively these results indicate that the levels of
      serum chemokines and the levels of expression of their respective chemokine
      receptors on T cell subsets may prove to be informative biomarkers for Lyme
      disease and related to specific disease manifestations. 

PMID- 24740101
TI  - Tidal stretches differently regulate the contractile and cytoskeletal elements in
      intact airways.
AB  - Recent reports suggest that tidal stretches do not cause significant and
      sustainable dilation of constricted intact airways ex vivo. To better understand
      the underlying mechanisms, we aimed to map the physiological stretch-induced
      molecular changes related to cytoskeletal (CSK) structure and contractile force
      generation through integrin receptors. Using ultrasound, we measured airway
      constriction in isolated intact airways during 90 minutes of static transmural
      pressure (Ptm) of 7.5 cmH2O or dynamic variations between Ptm of 5 and 10 cmH20
      mimicking breathing. Integrin and focal adhesion kinase activity increased during
      Ptm oscillations which was further amplified during constriction. While Ptm
      oscillations reduced beta-actin and F-actin formation implying lower CSK
      stiffness, it did not affect tubulin. However, constriction was amplified when
      the microtubule structure was disassembled. Without constriction, alpha-smooth
      muscle actin (ASMA) level was higher and smooth muscle myosin heavy chain 2 was
      lower during Ptm oscillations. Alternatively, during constriction, overall
      molecular motor activity was enhanced by Ptm oscillations, but ASMA level became
      lower. Thus, ASMA and motor protein levels change in opposite directions due to
      stretch and contraction maintaining similar airway constriction levels during
      static and dynamic Ptm. We conclude that physiological Ptm variations affect
      cellular processes in intact airways with constriction determined by the balance
      among contractile and CSK molecules and structure. 

PMID- 24740102
TI  - Climate variability and nonstationary dynamics of Mycoplasma pneumoniae pneumonia
      in Japan.
AB  - BACKGROUND: A stationary association between climate factors and epidemics of
      Mycoplasma pneumoniae (M. pneumoniae) pneumonia has been widely assumed. However,
      it is unclear whether elements of the local climate that are relevant to M.
      pneumoniae pneumonia transmission have stationary signatures of climate factors
      on their dynamics over different time scales. METHODS: We performed a cross
      wavelet coherency analysis to assess the patterns of association between monthly
      M. pneumoniae cases in Fukuoka, Japan, from 2000 to 2012 and indices for the
      Indian Ocean Dipole (IOD) and El Nino Southern Oscillation (ENSO). RESULTS:
      Monthly M. pneumoniae cases were strongly associated with the dynamics of both
      the IOD and ENSO for the 1-2-year periodic mode in 2005-2007 and 2010-2011. This
      association was non-stationary and appeared to have a major influence on the
      synchrony of M. pneumoniae epidemics. CONCLUSIONS: Our results call for the
      consideration of non-stationary, possibly non-linear, patterns of association
      between M. pneumoniae cases and climatic factors in early warning systems.

PMID- 24740100
TI  - A potent combination microbicide that targets SHIV-RT, HSV-2 and HPV.
AB  - Prevalent infection with human herpes simplex 2 (HSV-2) or human papillomavirus
      (HPV) is associated with increased human immunodeficiency virus (HIV)
      acquisition. Microbicides that target HIV as well as these sexually transmitted
      infections (STIs) may more effectively limit HIV incidence. Previously, we showed
      that a microbicide gel (MZC) containing MIV-150, zinc acetate (ZA) and
      carrageenan (CG) protected macaques against simian-human immunodeficiency virus
      (SHIV-RT) infection and that a ZC gel protected mice against HSV-2 infection.
      Here we evaluated a modified MZC gel (containing different buffers, co-solvents,
      and preservatives suitable for clinical testing) against both vaginal and rectal
      challenge of animals with SHIV-RT, HSV-2 or HPV. MZC was stable and safe in vitro
      (cell viability and monolayer integrity) and in vivo (histology). MZC protected
      macaques against vaginal (p<0.0001) SHIV-RT infection when applied up to 8 hours
      (h) prior to challenge. When used close to the time of challenge, MZC prevented
      rectal SHIV-RT infection of macaques similar to the CG control. MZC significantly
      reduced vaginal (p<0.0001) and anorectal (p = 0.0187) infection of mice when
      10(6) pfu HSV-2 were applied immediately after vaginal challenge and also when
      5*10(3) pfu were applied between 8 h before and 4 h after vaginal challenge
      (p<0.0248). Protection of mice against 8*10(6) HPV16 pseudovirus particles (HPV16
      PsV) was significant for MZC applied up to 24 h before and 2 h after vaginal
      challenge (p<0.0001) and also if applied 2 h before or after anorectal challenge
      (p<0.0006). MZC provides a durable window of protection against vaginal infection
      with these three viruses and, against HSV-2 and HPV making it an excellent
      candidate microbicide for clinical use.

PMID- 24740103
TI  - Association between the epidermal growth factor +61 G/A polymorphism and glioma
      risk: a meta-analysis.
AB  - BACKGROUND: Gliomas account for almost 80% of primary malignant brain tumors.
      Epidermal growth factor (EGF) is an interesting research candidate in which to
      look for genetic polymorphisms because of its role in mitogenesis and
      proliferation. Extensive studies have found that a single nucleotide polymorphism
      (SNP) +61 G/A (rs4444903) in the EGF gene is associated with the susceptibility
      of glioma, however, the results have been controversial. Furthermore, the
      association between EGF +61 G/A polymorphism with the development and grade
      progress of glioma has not been established. METHODS: We examined the association
      of EGF +61 G/A polymorphism and glioma by performing a meta-analysis. Nine
      studies testing the associations between EGF +61 G/A polymorphism and risk of
      glioma with 1758 cases and 2823 controls were retrieved. Odds ratios (ORs) and
      95% confidence intervals (CIs) were used to assess the strength of the
      association. The pooled ORs were performed for the allele model, codominant
      model, dominant model, and recessive model, respectively. RESULTS: Overall, this
      meta-analysis showed significant associations between the EGF +61 G/A
      polymorphism and glioma susceptibility in all four genetic models. However, in
      the stratified analysis by the grade of glioma, we only found this association
      existed in patients with Grade IV glioblastoma, but not in patients with Grade I
      III glioma. We further compared EGF +61 G/A polymorphism in patients with
      glioblastoma and Grade I-III glioma accordingly, the stronger association between
      the EGF +61 G/A polymorphism and the malignancy of glioma was found. CONCLUSIONS:
      The results of this meta-analysis suggested that the EGF +61 G/A polymorphism is
      associated with both the susceptibility of glioma and the malignance of glioma.

PMID- 24740104
TI  - Foreign body reaction associated with PET and PET/chitosan electrospun
      nanofibrous abdominal meshes.
AB  - Electrospun materials have been widely explored for biomedical applications
      because of their advantageous characteristics, i.e., tridimensional nanofibrous
      structure with high surface-to-volume ratio, high porosity, and pore
      interconnectivity. Furthermore, considering the similarities between the
      nanofiber networks and the extracellular matrix (ECM), as well as the accepted
      role of changes in ECM for hernia repair, electrospun polymer fiber assemblies
      have emerged as potential materials for incisional hernia repair. In this work,
      we describe the application of electrospun non-absorbable mats based on
      poly(ethylene terephthalate) (PET) in the repair of abdominal defects, comparing
      the performance of these meshes with that of a commercial polypropylene mesh and
      a multifilament PET mesh. PET and PET/chitosan electrospun meshes revealed good
      performance during incisional hernia surgery, post-operative period, and no
      evidence of intestinal adhesion was found. The electrospun meshes were flexible
      with high suture retention, showing tensile strengths of 3 MPa and breaking
      strains of 8-33%. Nevertheless, a significant foreign body reaction (FBR) was
      observed in animals treated with the nanofibrous materials. Animals implanted
      with PET and PET/chitosan electrospun meshes (fiber diameter of 0.71 +/- 0.28 um
      and 3.01 +/- 0.72 um, respectively) showed, respectively, foreign body granuloma
      formation, averaging 4.2-fold and 7.4-fold greater than the control commercial
      mesh group (Marlex). Many foreign body giant cells (FBGC) involving nanofiber
      pieces were also found in the PET and PET/chitosan groups (11.9 and 19.3 times
      more FBGC than control, respectively). In contrast, no important FBR was observed
      for PET microfibers (fiber diameter = 18.9 +/- 0.21 um). Therefore, we suggest
      that the reduced dimension and the high surface-to-volume ratio of the
      electrospun fibers caused the FBR reaction, pointing out the need for further
      studies to elucidate the mechanisms underlying interactions between cells/tissues
      and nanofibrous materials in order to gain a better understanding of the
      implantation risks associated with nanostructured biomaterials.

PMID- 24740105
TI  - Immunotherapy reduces allergen-mediated CD66b expression and myeloperoxidase
      levels on human neutrophils from allergic patients.
AB  - CD66b is a member of the carcinoembryonic antigen family, which mediates the
      adhesion between neutrophils and to endothelial cells. Allergen-specific
      immunotherapy is widely used to treat allergic diseases, and the molecular
      mechanisms underlying this therapy are poorly understood. The present work was
      undertaken to analyze A) the in vitro effect of allergens and immunotherapy on
      cell-surface CD66b expression of neutrophils from patients with allergic asthma
      and rhinitis and B) the in vivo effect of immunotherapy on cell-surface CD66b
      expression of neutrophils from nasal lavage fluid during the spring season.
      Myeloperoxidase expression and activity was also analyzed in nasal lavage fluid
      as a general marker of neutrophil activation. RESULTS: CD66b cell-surface
      expression is upregulated in vitro in response to allergens, and significantly
      reduced by immunotherapy (p<0.001). Myeloperoxidase activity in nasal lavage
      fluid was also significantly reduced by immunotherapy, as were the neutrophil
      cell-surface expression of CD66b and myeloperoxidase (p<0.001). Interestingly,
      CD66b expression was higher in neutrophils from nasal lavage fluid than those
      from peripheral blood, and immunotherapy reduced the number of CD66+MPO+ cells in
      nasal lavage fluid. Thus, immunotherapy positive effects might, at least in part,
      be mediated by the negative regulation of the CD66b and myeloperoxidase activity
      in human neutrophils.

PMID- 24740106
TI  - Endothelial dysfunction and brachial intima-media thickness: long term
      cardiovascular risk with claudication related to peripheral arterial disease: a
      prospective analysis.
AB  - OBJECTIVE: Endothelial dysfunction plays a key role in the development,
      progression, and clinical manifestation of atherosclerosis, and in symptomatic
      peripheral arterial disease, endothelial dysfunction and enlarged intima-media
      thickness might be associated with increased cardiovascular risk. Flow-mediated
      dilatation and serologic parameters are used to evaluate individual endothelial
      function. Brachial intima-media thickness, a less recognized parameter of
      cardiovascular risk, is independently associated with coronary artery disease.
      The aim of this study was to evaluate the prognostic value of ultrasound and
      serologic parameters of endothelial function in relation to cardiovascular
      mortality in peripheral arterial disease. DESIGN: monocentric, prospective cohort
      study. METHODS: Flow mediated dilatation and brachial intima-media thickness were
      assessed in 184 (124 male) patients with peripheral arterial disease (Rutherford
      stages 2-3). Serologic parameters of endothelial function included asymmetric
      dimethylarginine (ADMA), symmetric dimethylarginine (SDMA), and L-homoarginine.
      Cardiovascular events were recorded during a follow-up of 99.1+/-11.1 months.
      Subjects who died of noncardiovascular causes were excluded from further
      analysis. RESULTS: Eighty-two patients (44.6%) died during follow-up after a mean
      duration of 49.7+/-28.3 months. There were 49 cardiovascular deaths (59.8%) and
      33 other deaths (40.2%). Flow mediated dilatation was associated with
      cardiovascular death [1.17% (0.0, 4.3) vs. 4.1% (1.2, 6.4), p<0.001]. Intima
      media thickness was greater in patients who succumbed to cardiovascular disease
      [0.37 mm (0.30, 0.41)] than in survivors [0.21 mm (0.15, 0.38), p<0.001].
      Brachial intima-media thickness above 0.345 mm was most predictive of
      cardiovascular death, with sensitivity and specificity values of 0.714 and 0.657,
      respectively (p<0.001). Furthermore, ADMA levels above 0.745 umol/l and SDMA
      levels above 0.825 umol/l were significantly associated with cardiovascular death
      (p<0.001 and 0.030). CONCLUSION: In symptomatic peripheral arterial disease,
      decreased flow mediated dilatation, enlarged intima-media thickness, and elevated
      levels of ADMA and SDMA were associated with increased cardiovascular risk.

PMID- 24740107
TI  - Standardized posterior pelvic imaging: use of CT inlet and CT outlet for
      evaluation and management of pelvic ring injuries.
AB  - OBJECTIVES: The null hypothesis of this study states that routine axial computed
      tomography (CT) images are obtained at a consistent and reproducible orientation
      relative to the sacrum. The secondary null hypothesis states that there is no
      difference in the measurement of the safe zone for placement of iliosacral screws
      when using routine axial CT images and standardized reconstructions in defined
      planes perpendicular and parallel to the sacrum. DESIGN: Retrospective review.
      SETTING: University Level 1 Trauma Center. PATIENTS: Sixty-eight consecutive
      trauma patients evaluated with routine pelvic CT, without pelvic ring injury.
      INTERVENTION: Retrospective radiographic review and measurement. METHODS: Sixty
      eight consecutive adult patients with routine axial pelvic CT scans, without
      injury to the pelvic ring, and obtained as part of a trauma evaluation were
      retrospectively identified. The orientation of the axial slices relative to the
      sacrum was measured for each patient and compared. The maximal cross-sectional
      distance at the smallest section of the sacral ala (safe zone) was measured using
      the routine axial CT images, and these measurements were compared with similar
      measurements taken on standardized images perpendicular (CT inlet) and parallel
      (CT outlet) to the body of the sacrum. Additional data referencing the
      orientation of multiple sacral radiographic landmarks were also collected.
      RESULTS: The orientation of routine axial CT image planes relative to the sacrum
      spanned a wide range. The angle between the routine axial CT plane and the sacrum
      varied from 43.5 to 82.0 degrees (SD = 9 degrees). Significant differences were
      found in measured safe zones of routine axial CT images compared with
      standardized CT inlet and CT outlet images. Compared with CT inlet images,
      routine axial CT images underestimated safe zones for transverse sacral screws at
      both S1 (P < 0.01) and S2 (P < 0.01). When compared with CT outlet images,
      routine axial CT images overestimated safe zones for oblique sacroiliac screws (P
      < 0.01) and underestimated the safe zone for S2 transverse sacral style screws (P
      < 0.01). No significant differences in measured variables were found between
      genders and sacral morphology. CONCLUSIONS: Our null hypotheses were rejected:
      routine axial CT images were found to be at widely ranging orientations relative
      to the sacrum, and standardized CT images (CT inlet and CT outlet) demonstrated
      statistically significant differences in measurements of safe zones compared with
      routine axial CT images. Furthermore, the CT inlet and CT outlet views provide
      additional information regarding sacral landmarks that could be useful for
      preoperative planning.

PMID- 24740108
TI  - Determining the efficacy of screw and washer fixation as a method for securing
      olecranon osteotomies used in the surgical management of intraarticular distal
      humerus fractures.
AB  - OBJECTIVES: The purpose of this study was to critically evaluate the efficacy of
      single screw and washer fixation in comparison with other methods for securing
      olecranon osteotomies. The hypothesis is that screw and washer fixation is a safe
      and effective means of olecranon osteotomy fixation with fusion and complication
      rates similar to other methods of fixation. DESIGN: Retrospective review.
      SETTING: Two Level I Urban Trauma Centers. PATIENTS/PARTICIPANTS: Patients were
      treated within the last 20 years and received 1 of 4 types of fixation (screw and
      washer alone, screw and washer augmented with tension band, tension band alone,
      or plate and screws) after osteotomy. INTERVENTION: Open reduction and internal
      fixation of OTA/AO 13B/C distal humerus fractures with an olecranon osteotomy.
      MAIN OUTCOME MEASUREMENTS: The primary outcome measure was the presence of
      osteotomy union. Secondary outcome measures were olecranon nonunion, loss of
      articular reduction, and removal of hardware. Logistic regression was used to
      determine the associations between method of osteotomy fixation and removal of
      hardware or nonunion rates. Comorbidities were stratified using the Charlson
      comorbidity index. RESULTS: One hundred sixty patients met the inclusion
      criteria. Thirty-nine patients underwent screw fixation alone, 47 had tension
      band fixation, 16 had plate fixation, and 58 had tension band and screw fixation.
      Screw fixation demonstrated equal or better rates of union, maintenance of
      reduction, absence of infection, and implant removal compared with alternative
      fixation techniques. Higher Charlson scores were associated with higher rates of
      nonunion. CONCLUSIONS: Screw and washer fixation is a safe and effective means of
      securing an olecranon osteotomy. Charlson comorbidity score is one factor that
      may influence the development of nonunion after osteotomy. LEVEL OF EVIDENCE:
      Therapeutic Level III. See Instructions for Authors for a complete description of
      levels of evidence.

PMID- 24740109
TI  - Altered lower extremity fracture characteristics in obese pediatric trauma
      patients.
AB  - OBJECTIVE: To determine whether there are differences in fracture patterns and
      femur fracture treatment choices in obese versus nonobese pediatric trauma
      patients. DESIGN: Prognostic study, retrospective chart review. SETTING: Two
      level I pediatric trauma centers. PATIENTS: The trauma registries of 2 pediatric
      hospitals were queried for patients with lower extremity long-bone fractures
      resulting from blunt trauma. 2858 alerts were examined, and 397 patients had
      lower extremity fractures. Three hundred thirty-one patients with a total of 394
      femur or tibia fractures met the inclusion criteria, and 70 patients (21%) were
      obese. MAIN OUTCOME MEASUREMENTS: Weight for age >95th percentile was defined as
      obese. Radiographs were reviewed, and fractures were classified according the
      OTA/AO pediatric fracture classification system. Fracture patterns (OTA
      subsegment), severity, and choice of intervention for femur fractures were the
      primary outcomes. RESULTS: Overall, obese patients were twice as likely [risk
      ratio (RR), 2.20; 95% confidence interval (CI), 1.25-3.89] to have fractures
      involving the physis. Physeal fracture risk was greater for femur fractures (RR,
      3.25; 95% CI, 1.35-7.78) than tibia fractures (RR, 1.58; 95% CI, 0.76-3.26).
      Severity did not differ between groups. Obese patients with femur fractures were
      more likely to be treated with locked nails. CONCLUSIONS: Obese pediatric trauma
      patients are more likely to sustain fractures involving the physis than nonobese
      patients. This could be related to intrinsic changes to the physis related to
      obesity or altered biomechanical forces. This is consistent with the observed
      relationships between obesity and other conditions affecting the physis including
      Blount disease and slipped capital femoral epiphysis. LEVEL OF EVIDENCE:
      Prognostic Level II. See Instructions for Authors for a complete description of
      levels of evidence.

PMID- 24740110
TI  - Nonoperative treatment of intermediate severity lateral compression type 1 pelvic
      ring injuries with minimally displaced complete sacral fracture.
AB  - OBJECTIVES: Controversy exists regarding optimum management of lateral
      compression type 1 (LC1) pelvic ring injuries (OTA type 61-B2.1), particularly in
      patients with complete sacral fractures. We hypothesized that nonoperative
      treatment would result in acceptable functional outcomes. DESIGN: Database
      review. SETTING: Level I trauma center. PATIENTS: We identified patients treated
      for LC1 fractures (n = 406) from 2007 to 2011 and analyzed a subset of LC1
      injuries of "intermediate severity" characterized by complete sacral fracture
      with less than 1 cm initial displacement (n = 104). INTERVENTION: Fifty patients
      were contacted for functional outcome assessment at average follow-up of 33
      months. MAIN OUTCOME MEASURES: Majeed pelvic score and physical component summary
      (PCS) score and mental component summary (MCS) score of 12-item Short-Form Health
      Survey version 2. RESULTS: Average Majeed pelvic score was 85.5, yielding 33
      excellent, 9 good, 5 fair, and 3 poor outcomes. Mean PCS and MCS scores were 48.8
      and 48.9, respectively (both confidence intervals include 50, the score for a
      healthy normative population). Patients with lower extremity injuries had a trend
      toward lower PCS and MCS and statistically significant lower mean Majeed scores
      (P = 0.01). Thirty-five of 37 patients without lower extremity injury had good or
      excellent categorical outcomes based on Majeed scores. No significant differences
      were observed regarding weight-bearing status, extent of anterior ring injury, or
      injury severity score. Radiographic follow-up was available for 36 of 50
      patients. No fracture was displaced >1 cm. CONCLUSIONS: Acceptable functional
      outcomes can be expected after nonsurgical management of LC1 pelvic injuries with
      complete sacral fracture and less than 1 cm initial displacement. LEVEL OF
      EVIDENCE: Therapeutic level IV.

PMID- 24740111
TI  - Reasons for transfer to a level 1 trauma center and barriers to timely definitive
      fracture fixation.
AB  - OBJECTIVE: Our purpose was to compare patients transferred from another hospital
      to our trauma center with those arriving directly, to identify barriers to care
      for similar fractures. We hypothesized that the most frequent reason for delayed
      definitive fixation would be interhospital transfer and that patients would be
      transferred primarily for 2 reasons: complex patients with more severe injuries
      and less complex patients without insurance. DESIGN: Retrospective review.
      SETTING: Level 1 trauma center. PATIENTS/PARTICIPANTS: A total of 1549 skeletally
      mature patients with 1655 fractures: 379 acetabulum, 301 pelvic ring, 876 femur,
      and 99 spine. INTERVENTION: All patients were treated surgically, with early
      fixation defined as <24 hours after injury. MAIN OUTCOME MEASUREMENTS:
      Demographic and injury characteristics were recorded. Reasons for and timing of
      transfer were determined. RESULTS: A total of 814 patients (53%) were transferred
      from another hospital, including 66% of acetabular and 62% of pelvic ring
      fractures. Transferred patients were older (39.1 vs. 36.6 years, P = 0.002), had
      more commercial insurance (21% vs. 17%, P = 0.10), and were less often uninsured
      (27% vs. 31%, P = 0.11). However, the mean Injury Severity Score of uninsured
      transferred patients was lower than that of the other transferred patients (22.9
      vs. 25.8, P < 0.0001). Transfer was not related to weekday or time of injury. A
      total of 973 patients (63%) had early definitive fixation. Delayed fixation was
      often for surgeon preference (57%). Transferred patients were more likely to have
      delayed fixation (43% vs. 31% of nontransferred, P < 0.0001). CONCLUSIONS:
      Internal barriers to definitive fracture care were noted, the most frequent of
      which is surgeon preference. Treatment delays due to transfer accounted for 12%
      of all delays. Many transferred patients appeared appropriate based on injury
      complexity. However, over one-fourth of those transferred had low Injury Severity
      Score and a significantly higher incidence of no insurance. Communication and
      transparency about these issues may serve to expedite care and to enhance
      financial stability of larger trauma centers. LEVEL OF EVIDENCE: Prognostic level
      II.

PMID- 24740112
TI  - Pediatric refracture rates after angulated and completely displaced clavicle
      shaft fractures.
AB  - OBJECTIVES: The purpose of this study was to assess refracture rates after
      angulation-only and completely displaced clavicle shaft fractures in children.
      DESIGN: Retrospective chart review. SETTING: Level 1 pediatric trauma center.
      PATIENTS: Computerized medical records searches identified children treated
      nonoperatively for clavicle shaft fractures at our institution. Inclusion
      criteria were age less than 18 years and a minimum of 1-year radiographic follow
      up. Statistical methods included Fisher exact test with significant probability
      values being defined as less than 0.05. RESULTS: Of the 120 angulation-only
      patients and 41 completely displaced patients meeting criteria for inclusion in
      our study, we identified a statistically higher (P = 0.002) refracture rate (18%,
      21/120) in angulation-only fractures as compared with 0% (0/41) for completely
      displaced fractures. Subgroup analysis of the angulation-only fractures revealed
      that fractures angulated less than 40 degrees refractured at a 26% rate (18/69)
      versus 6% (3/51) of fractures with greater angulation (P = 0.004). CONCLUSIONS:
      We found that angulation-only shaft fractures had a significantly higher
      refracture rate than completely displaced fractures. Furthermore, subgroup
      analysis demonstrated that less-angulated fractures had a higher refracture rate
      than the more-angulated ones. We feel this somewhat paradoxical finding is
      analogous to fractures of the forearm shaft, for which greenstick fractures
      refracture at a higher rate than complete forearm shaft fractures due to less
      exuberant callus formation. LEVEL OF EVIDENCE: Prognostic level III. See
      instructions for authors for a complete description of levels of evidence.

PMID- 24740113
TI  - Upright versus supine radiographs of clavicle fractures: does positioning matter?
AB  - OBJECTIVES: To determine whether clavicle fracture displacement and shortening
      are different between upright and supine radiographic examinations. DESIGN:
      Combined retrospective and prospective comparative study. SETTING: Level I Trauma
      Center. PATIENTS: Forty-six patients (mean age, 49 years; range, 24-89 years)
      with an acute clavicle fracture were evaluated. INTERVENTION: Standardized
      clavicle radiographs were obtained in both supine and upright positions for each
      patient. Displacement and shortening were measured and compared between the 2
      positions. MAIN OUTCOMES MEASUREMENTS: One resident and 3 traumatologists
      classified the fractures and measured displacement and shortening. Data were
      aggregated and compared to ensure reliability with a 2-way mixed intraclass
      correlation. RESULTS: Fracture displacement was significantly greater when
      measured from upright radiographs (15.9 +/- 8.9 mm) than from supine radiographs
      (8.4 +/- 6.6 mm, P < 0.001), representing an 89% increase in displacement with
      upright positioning. Forty-one percent of patients had greater than 100%
      displacement on upright but not on supine radiographs. Compared with the
      uninjured side, 3.0 +/- 10.7 mm of shortening was noted on upright radiographs
      and 1.3 +/- 9.5 mm of lengthening on supine radiographs (P < 0.001). The
      intraclass correlation was 0.82 [95% confidence interval (CI), 0.73-0.89] for OTA
      fracture classification, 0.81 (95% CI, 0.75-0.87) for vertical displacement, and
      0.92 (95% CI, 0.88-0.95) for injured clavicle length, demonstrating very high
      agreement among evaluators. CONCLUSIONS: Increased fracture displacement and
      shortening was observed on upright compared with supine radiographs. This
      suggests that upright radiographs may better demonstrate clavicle displacement
      and predict the position at healing if nonoperative treatment is selected.

PMID- 24740114
TI  - Functional and quality-of-life results of displaced and nondisplaced proximal
      humeral fractures treated conservatively.

PMID- 24740115
TI  - The impact of suicidality-related internet use: a prospective large cohort study
      with young and middle-aged internet users.
AB  - BACKGROUND: There has been no study that has allowed clear conclusions about the
      impact of suicide-related or mental health consultation-related internet use.
      AIM: To investigate the impacts of suicide-related or mental health consultation
      related internet use. METHODS: We conducted prospective observational
      longitudinal study with data collection at baseline screening (T0), 1 week after
      T0 (T1) and 7 weeks after T0 (T2). Participants with a stratified random sampling
      from 744,806 internet users were 20-49 years of age who employed the internet for
      suicide-related or mental health consultation-related reasons and internet users
      who did not. The main outcome was suicidal ideation. Secondary outcome measures
      comprised hopelessness, depression/anxiety, and loneliness. RESULTS: The internet
      users who had employed the internet for suicide-related or mental health
      consultation-related reasons at T0 (n = 2813), compared with those who had not (n
      = 2682), showed a significant increase in suicidal ideation (beta = 0.38, 95%CI:
      0.20-0.55) and depression/anxiety (beta = 0.37, 95%CI: 0.12-0.61) from T1 to T2.
      Those who disclosed their own suicidal ideation and browsed for information about
      suicide methods on the web showed increased suicidal ideation (beta = 0.55,
      95%CI: 0.23-0.88; beta = 0.45, 95% CI: 0.26-0.63, respectively). Although mental
      health consultation with an anonymous other online did not increase suicidal
      ideation, increased depression/anxiety was observed (beta = 0.34, 95%CI: -0.03
      0.71). CONCLUSIONS: An increased suicidal ideation was observed in the young and
      middle-aged who employed the internet for suicide-related or mental health
      consultation-related reasons. Mental health consultation via the internet was not
      useful, but those who did so showed worsened depression/anxiety.

PMID- 24740117
TI  - Population-level correlates of preterm delivery among black and white women in
      the U.S.
AB  - OBJECTIVE: This study examined the ability of social, demographic, environmental
      and health-related factors to explain geographic variability in preterm delivery
      among black and white women in the US and whether these factors explain black
      white disparities in preterm delivery. METHODS: We examined county-level
      prevalence of preterm delivery (20-31 or 32-36 weeks gestation) among singletons
      born 1998-2002. We conducted multivariable linear regression analysis to estimate
      the association of selected variables with preterm delivery separately for each
      preterm/race-ethnicity group. RESULTS: The prevalence of preterm delivery varied
      two- to three-fold across U.S. counties, and the distributions were strikingly
      distinct for blacks and whites. Among births to blacks, regression models
      explained 46% of the variability in county-level risk of delivery at 20-31 weeks
      and 55% for delivery at 32-36 weeks (based on R-squared values). Respective
      percentages for whites were 67% and 71%. Models included socio
      environmental/demographic and health-related variables and explained similar
      amounts of variability overall. CONCLUSIONS: Much of the geographic variability
      in preterm delivery in the US can be explained by socioeconomic, demographic and
      health-related characteristics of the population, but less so for blacks than
      whites.

PMID- 24740116
TI  - Description of Colponema vietnamica sp.n. and Acavomonas peruviana n. gen. n.
      sp., two new alveolate phyla (Colponemidia nom. nov. and Acavomonidia nom. nov.)
      and their contributions to reconstructing the ancestral state of alveolates and
      eukaryotes.
AB  - The evolutionary and ecological importance of predatory flagellates are too often
      overlooked. This is not only a gap in our understanding of microbial diversity,
      but also impacts how we interpret their better-studied relatives. A prime example
      of these problems is found in the alveolates. All well-studied species belong to
      three large clades (apicomplexans, dinoflagellates, and ciliates), but the
      predatory colponemid flagellates are also alveolates that are rare in nature and
      seldom cultured, but potentially important to our understanding of alveolate
      evolution. Recently we reported the first cultivation and molecular analysis of
      several colponemid-like organisms representing two novel clades in molecular
      trees. Here we provide ultrastructural analysis and formal species descriptions
      for both new species, Colponema vietnamica n. sp. and Acavomonas peruviana n.
      gen. n. sp. Morphological and feeding characteristics concur with molecular data
      that both species are distinct members of alveolates, with Acavomonas lacking the
      longitudinal phagocytotic groove, a defining feature of Colponema. Based on
      ultrastructure and molecular phylogenies, which both provide concrete rationale
      for a taxonomic reclassification of Alveolata, we establish the new phyla
      Colponemidia nom. nov. for the genus Colponema and its close relatives, and
      Acavomonidia nom. nov. for the genus Acavomonas and its close relatives. The
      morphological data presented here suggests that colponemids are central to our
      understanding of early alveolate evolution, and suggest they also retain features
      of the common ancestor of all eukaryotes. 

PMID- 24740118
TI  - Long-term functional outcomes and subclavian vein patency in patients undergoing
      thoracic outlet surgery for Paget-Schroetter Syndrome.
AB  - BACKGROUND: To assess subclavian vein (SCV) patency and long-term functional
      outcomes following surgical decompression of the thoracic outlet (SDTO) for Paget
      Schroetter Syndrome (PSS). METHODS: Between January 1978 and January 2013, we
      identified 33 patients with PSS who underwent SDTO. Demographic, clinical and
      radiological data were extracted from electronic databases and patient records.
      All patients were invited to update their follow-up data during dedicated
      outpatient visits between October and December 2013. Outcome measures included
      long-term SCV patency and clinical success rates during follow-up. Clinical
      success was defined as the combined absence of functional symptoms and patient's
      ability to maintain normal professional activities at final follow-up. The
      QuickDASH score was also determined. RESULTS: The study population comprised 17
      men and 16 women (mean age 34 years; range: 14-53 years) with PSS. Diagnosis was
      reached by venography (29 cases) or duplex scan (4 cases). SDTO was performed via
      the transaxillary route (25 cases) or using the combined supra-infraclavicular
      approach (8 cases). The procedure was carried out within 10 days in 13 patients
      (early-group), and between 30 to 120 days in the remaining 20 patients (late
      group). The former had SCV recanalization obtained actively by thrombolysis (3
      cases), thrombectomy (9 cases) or endovenectomy followed by patch venoplasty (1
      case). The latter were maintained under chronic oral anticoagulation to allow SCV
      recanalization. There was neither postoperative death nor major bleeding
      complications. At a median follow-up of 240 months, 11 SCV remained patent in the
      early group, while in the other there was 3 re-occlusions, 4 residual stenoses
      and 5 chronic SCV occlusions. Clinical success was achieved in 73% of patients
      for the whole cohort, but was significantly better in patients operated on in the
      early stages (100% vs. 55%; P=0.005). The mean Quick Disabilities of the Arm,
      Shoulder, and Hand Score was 3.5 (95% CI: 1.5-5.4) in the early-group and 17.3
      (95% CI: 8.4-26.2) in the late-group (P=0.01). CONCLUSIONS: Our data shows that
      long-term functional outcomes and SCV patency remained better in PSS patients who
      underwent early SDTO and active SCV recanalization techniques.

PMID- 24740119
TI  - The prognostic significance of proliferative indices in surgically resected IIIA
      N2 non-small cell lung cancer after induction chemotherapy.
AB  - BACKGROUND: The aim of this study was to assess the prognostic significance of
      Mib1 expression, Mitosis (Mi) and Apoptosis (Ai) in residual tumour cells after
      induction chemotherapy in surgically resected IIIA-N2 patients. METHODS: Between
      January 2002 and November 2008, we reviewed 50 consecutive patients (39 males)
      with histologically proven stage IIIA-N2 non-small cell lung cancer (NSCLC), who
      underwent radical resection following induction chemotherapy. Five-year survival
      in the series was evaluated in relation to lymph node downstaging, histology,
      extent of resection, number of chemotherapy cycles, pT status, sex and age. It
      was then also evaluated in relation to the proliferative indexes (Mi, Ap and Mib
      1 expression), dividing the patients into two groups according to whether they
      were above or below the 50th percentile for each parameter. The associations
      between mortality and the abovementioned prognostic factors were explored using
      the Kaplan-Meier method, the log-rank test, and Cox regression analysis. RESULTS:
      The monovariate analysis confirmed the positive prognostic role of lymph node
      downstaging in terms of 5-yr survival: 31% vs. 12% (P=0.018). However Mi and Mib1
      expression under the 50th percentile were also associated with better 5-yr
      survival: respectively 46% vs. 5% (P=0.007) and 40% vs. 6% (P=0.017). Neither
      apoptosis nor the other prognostic factors showed any statistical impact on long
      term survival. The multivariate analysis showed Mi to be an independent
      prognostic factor (P=0.005). CONCLUSIONS: Although lymph node downstaging has
      been considered the principal prognostic factor after induction chemotherapy and
      surgical resection, Mi and Mib1 expression in residual tumor can predict long
      term survival more accurately.

PMID- 24740121
TI  - The uptake mechanism and biocompatibility of graphene quantum dots with human
      neural stem cells.
AB  - Cellular imaging after transplantation may provide important information to
      determine the efficacy of stem cell therapy. We have reported that graphene
      quantum dots (GQDs) are a type of robust biological labeling agent for stem cells
      that demonstrate little cytotoxicity. In this study, we examined the interactions
      of GQDs on human neural stem cells (hNSCs) with the aim to investigate the uptake
      and biocompatibility of GQDs. We examined the mechanism of GQD uptake by hNSCs
      and investigated the effects of GQDs on the proliferation, metabolic activity,
      and differentiation potential of hNSCs. This information is critical to assess
      the suitability of GQDs for stem cell tracking. Our results indicated that GQDs
      were taken up into hNSCs in a concentration- and time-dependent manner via the
      endocytosis mechanism. Furthermore, no significant change was found in the
      viability, proliferation, metabolic activity, and differentiation potential of
      hNSCs after treatment with GQDs. Thus, these data open a promising avenue for
      labeling stem cells with GQDs and also offer a potential opportunity to develop
      GQDs for biomedical applications. 

PMID- 24740120
TI  - Proteinase-Activated Receptor 1 (PAR1) regulates leukemic stem cell functions.
AB  - External signals that are mediated by specific receptors determine stem cell
      fate. The thrombin receptor PAR1 plays an important role in haemostasis,
      thrombosis and vascular biology, but also in tumor biology and angiogenesis. Its
      expression and function in hematopoietic stem cells is largely unknown. Here, we
      analyzed expression and function of PAR1 in primary hematopoietic cells and their
      leukemic counterparts. AML patients' blast cells expressed much lower levels of
      PAR1 mRNA and protein than CD34+ progenitor cells. Constitutive Par1-deficiency
      in adult mice did not affect engraftment or stem cell potential of hematopoietic
      cells. To model an AML with Par1-deficiency, we retrovirally introduced the
      oncogene MLL-AF9 in wild type and Par1-/- hematopoietic progenitor cells. Par1
      deficiency did not alter initial leukemia development. However, the loss of Par1
      enhanced leukemic stem cell function in vitro and in vivo. Re-expression of PAR1
      in Par1-/- leukemic stem cells delayed leukemogenesis in vivo. These data
      indicate that Par1 contributes to leukemic stem cell maintenance. 

PMID- 24740122
TI  - Muon spin spectroscopy of ferrocene: characterization of muoniated ferrocenyl
      radicals.
AB  - Radicals formed by the reaction of muonium (Mu), a light isotope of hydrogen,
      with ferrocene and ferrocene-d10 have been studied with the avoided level
      crossing muon spin resonance (ALC-MUSR) and longitudinal field muon spin
      relaxation (LF-MUSR) techniques between 10 and 100 K. A single type of radical
      was observed in each compound and the muon hyperfine coupling constants (hfcc)
      and the muon spin relaxation rates were measured as a function of temperature. A
      previous report concerning the observation of Mu adducts of ferrocene (U. A.
      Jayasooriya et al. Chem. - Eur. J., 2007, 13, 2266-2276) appears to be incorrect.
      DFT calculations were performed to aid in the assignment of the ALC-MUSR spectra.
      A tentative assignment is that the observed radicals were formed by Mu addition
      to the exterior of the cyclopentadienyl rings and that the structures are
      distorted due to interactions with neighbouring molecules. The temperature
      dependence of the muon hfcc can be explained assuming the population of two
      levels with different muon hfccs separated by 1.4 +/- 0.1 kJ mol(-1). The
      temperature dependence of the width and amplitude of the Delta1 resonance and the
      muon spin relaxation rate suggests that the electron spin relaxation rate
      increase with temperature, but the relaxation mechanism is unknown. 

PMID- 24740123
TI  - Homophily and the speed of social mobilization: the effect of acquired and
      ascribed traits.
AB  - Large-scale mobilization of individuals across social networks is becoming
      increasingly prevalent in society. However, little is known about what affects
      the speed of social mobilization. Here we use a framed field experiment to
      identify and measure properties of individuals and their relationships that
      predict mobilization speed. We ran a global social mobilization contest and
      recorded personal traits of the participants and those they recruited. We studied
      the effects of ascribed traits (gender, age) and acquired traits (geography, and
      information source) on the speed of mobilization. We found that homophily, a
      preference for interacting with other individuals with similar traits, had a
      mixed role in social mobilization. Homophily was present for acquired traits, in
      which mobilization speed was faster when the recuiter and recruit had the same
      trait compared to different traits. In contrast, we did not find support for
      homophily for the ascribed traits. Instead, those traits had other, non-homophily
      effects: Females mobilized other females faster than males mobilized other males.
      Younger recruiters mobilized others faster, and older recruits mobilized slower.
      Recruits also mobilized faster when they first heard about the contest directly
      from the contest organization, and decreased in speed when hearing from less
      personal source types (e.g. family vs. media). These findings show that social
      mobilization includes dynamics that are unlike other, more passive forms of
      social activity propagation. These findings suggest relevant factors for
      engineering social mobilization tasks for increased speed. 

PMID- 24740124
TI  - Obesity.

PMID- 24740125
TI  - Public health: Society at large.

PMID- 24740126
TI  - Cell physiology: The changing colour of fat.

PMID- 24740128
TI  - Perspective: Obesity is not a disease.

PMID- 24740127
TI  - Treatment: Marginal gains.

PMID- 24740129
TI  - Heritability: The family roots of obesity.

PMID- 24740130
TI  - Microbiome: A complicated relationship status.

PMID- 24740131
TI  - Neuroscience: Dissecting appetite.

PMID- 24740132
TI  - Perspective: Tricks of the trade.

PMID- 24740133
TI  - Examining the cognitive model of caregiving--a structural equation modelling
      approach.
AB  - The study tests assumptions from the "cognitive model of caregiving" (Kuipers et
      al., 2010), which aims to inform interventions for carers of people with
      psychoses. The sample comprised 61 relatives of patients with schizophrenia.
      Standardized psychological assessments were conducted twice within 6 months
      including Involvement Evaluation Questionnaire (IEQ-EU), a short form of the
      Symptom Checklist 90-R (SCL K9), the Family Questionnaire (FQ), scales measuring
      control attributions of the Illness Perception Questionnaire for Schizophrenia
      (IPQS-R) and emotions toward the ill relative. Structural equation modelling was
      used to analyse data. We identified two pathways: (a) from "attributing control
      to relatives" to distress, intermediated by anxiety for the patient and emotional
      overinvolvement (EOI), and (b) from "attribution control to patient" to distress,
      intermediated by anger about the patient and criticism. The model provided a good
      fit to the data and was successfully replicated at a second point in time. We
      were able to find supporting evidence for a cognitive model of caregiving.
      Control attributions and emotions of informal caregivers are important when
      interventions are planned reducing expressed emotion and burden of caregivers. 

PMID- 24740134
TI  - A Novel Drug for Treatment of Necrotizing Soft-Tissue Infections: A Randomized
      Clinical Trial.
AB  - IMPORTANCE: Necrotizing soft-tissue infections (NSTI) have high morbidity and
      mortality rates despite aggressive surgical debridement and antibiotic therapy.
      AB103 is a peptide mimetic of the T-lymphocyte receptor, CD28. We hypothesized
      that AB103 will limit inflammatory responses to bacterial toxins and decrease the
      incidence of organ failure. OBJECTIVES: To establish the safety of AB103 in
      patients with NSTI and evaluate the potential effects on clinically meaningful
      parameters related to the disease. DESIGN, SETTING, AND PARTICIPANTS: A
      prospective, randomized, placebo-controlled, double-blinded study was performed
      in 6 academic medical centers in the United States. Participants included adults
      with NSTI. Of 345 patients screened, 43 were enrolled for the intent-to-treat
      analysis, and 40 met criteria for the modified intent-to-treat analysis; 15
      patients each were included in the high-dose and low-dose treatment arms, and 10
      in the placebo arm. INTERVENTION: Single intravenous dose of AB103 (0.5 or 0.25
      mg/kg) within 6 hours after diagnosis of NSTI. MAIN OUTCOMES AND MEASURES: Change
      in the Sequential Organ Failure Assessment score within 28 days, intensive care
      unit-free and ventilator-free days, number and timing of debridements, plasma and
      tissue cytokine levels at 0 to 72 hours, and adverse events. RESULTS: Baseline
      characteristics were comparable in the treatment groups. The Sequential Organ
      Failure Assessment score improved from baseline in both treatment groups compared
      with the placebo group at 14 days (change from baseline score, -2.8 in the high
      dose, -2 in the low-dose, and +1.3 in the placebo groups; P = .04). AB103-treated
      patients had a similar number of debridements (mean [SD], 2.2 [1.1] for the high
      dose, 2.3 [1.2] for the low-dose, and 2.8 [2.1] for the placebo groups; P = .56).
      There were no statistically significant differences in intensive care unit-free
      and ventilator-free days or in plasma and tissue cytokine levels. No drug-related
      adverse events were detected. CONCLUSIONS AND RELEVANCE: AB103 is a safe,
      promising new agent for modulation of inflammation after NSTI. Further study is
      warranted to establish efficacy. TRIAL REGISTRATION: clinicaltrials.gov
      Identifier: NCT01417780.

PMID- 24740135
TI  - Anti-oxidative defences are modulated differentially in three freshwater teleosts
      in response to ammonia-induced oxidative stress.
AB  - Oxidative stress and the antioxidant response induced by high environmental
      ammonia (HEA) were investigated in the liver and gills of three freshwater
      teleosts differing in their sensitivities to ammonia. The highly ammonia
      sensitive salmonid Oncorhynchus mykiss (rainbow trout), the less ammonia
      sensitive cyprinid Cyprinus carpio (common carp) and the highly ammonia-resistant
      cyprinid Carassius auratus (goldfish) were exposed to 1 mM ammonia (as NH4HCO3)
      for 0 h (control), 3 h, 12 h, 24 h, 48 h, 84 h and 180 h. Results show that HEA
      exposure increased ammonia accumulation significantly in the liver of all the
      three fish species from 24 h-48 h onwards which was associated with an increment
      in oxidative stress, evidenced by elevation of xanthine oxidase activity and
      levels of hydrogen peroxide (H2O2) and malondialdehyde (MDA). Unlike in trout,
      H2O2 and MDA accumulation in carp and goldfish liver was restored to control
      levels (84 h-180 h); which was accompanied by a concomitant increase in
      superoxide dismutase (SOD), catalase (CAT), ascorbate peroxidase activity and
      reduced ascorbate content. Many of these defence parameters remained unaffected
      in trout liver, while components of the glutathione redox cycle (reduced
      glutathione, glutathione peroxidase and glutathione reductase) enhanced to a
      greater extent. The present findings suggest that trout rely mainly on
      glutathione dependent defensive mechanism while carp utilize SOD, CAT and
      ascorbate as anti-oxidative sentinels. Hepatic cells of goldfish appear to
      utilize each of these protective systems, and showed more effective anti
      oxidative compensatory responses towards HEA than carp, while trout were least
      effective. The present work also indicates that HEA exposure resulted in a
      relatively mild oxidative stress in the gills of all three species. This probably
      explains the almost complete lack of anti-oxidative responses in branchial
      tissue. This research suggests that oxidative stress, as well as the antioxidant
      potential clearly differ between salmonid and cyprinid species. 

PMID- 24740136
TI  - Management options in locally advanced pancreatic cancer.
AB  - Pancreatic ductal adenocarcinoma is a highly lethal cancer that is rarely curable
      at the time of presentation. Unfortunately, most patients are diagnosed with
      either metastatic or locally advanced disease, which is not amenable to surgery
      owing to the high likelihood of incomplete resection. Given the generally poor
      prognosis with propensity for metastatic failure greater than that for local
      failure, treatment options are variable, and include chemotherapy, radiotherapy,
      targeted therapies, and combinations thereof. This review summarizes the current
      evidence for definitive management of locally advanced pancreatic adenocarcinoma,
      as well as the role of palliative therapies. Future directions, including the
      development of predictive biomarkers and novel systemic agents, are also
      discussed. 

PMID- 24740138
TI  - A small subset of fruitless subesophageal neurons modulate early courtship in
      Drosophila.
AB  - We show that a small subset of two to six subesophageal neurons, expressing the
      male products of the male courtship master regulator gene products fruitless Male
      (fru M), are required in the early stages of the Drosophila melanogaster male
      courtship behavioral program. Loss of fru M expression or inhibition of synaptic
      transmission in these fru M(+) neurons results in delayed courtship initiation
      and a failure to progress to copulation primarily under visually-deficient
      conditions. We identify a fru M-dependent sexually dimorphic arborization in the
      tritocerebrum made by two of these neurons. Furthermore, these SOG neurons extend
      descending projections to the thorax and abdominal ganglia. These anatomical and
      functional characteristics place these neurons in the position to integrate
      gustatory and higher-order signals in order to properly initiate and progress
      through early courtship.

PMID- 24740137
TI  - Comparison of safety, efficacy and tolerability of dexibuprofen and ibuprofen in
      the treatment of osteoarthritis of the hip or knee.
AB  - In this observer-blinded, multicenter, non-inferiority study, 489 patients
      suffering from painful osteoarthritis of the hip or knee were included to
      investigate safety and tolerability of Dexibuprofen vs. Ibuprofen powder for oral
      suspension. Only patients who had everyday joint pain for the past 3 months and
      "moderate" to "severe" global pain intensity in the involved hip/knee of within
      the last 48 h were enrolled. The treatment period was up to 14 days with a
      control visit after 3 days. The test product was Dexibuprofen 400 mg powder for
      oral suspension (daily dose 800 mg) compared to Ibuprofen 400 mg powder for oral
      suspension (daily dose 1,600 mg). Gastrointestinal adverse drug reactions were
      reported in 8 patients (3.3 %) in the Dexibuprofen group and in 19 patients (7.8
      %) in the Ibuprofen group. Statistically significant non-inferiority was shown
      for Dexibuprofen. Comparing both groups by a Chi square test showed a statistical
      significant lower proportion of related gastrointestinal events in the
      Dexibuprofen group. All analyses of secondary tolerability parameters showed the
      same result of a significantly better safety profile in this therapy setting for
      Dexibuprofen compared to Ibuprofen. The sum of pain intensity, pain relief and
      global assessments showed no significant difference between treatment groups. In
      summary, analyses revealed at least non-inferiority in terms of efficacy and a
      statistically significant better safety profile for the Dexibuprofen treatment. 

PMID- 24740139
TI  - One-pot synthesis of ultralong coaxial Au@Pt nanocables with numerous highly
      catalytically active perpendicular twinning boundaries and Au@Pt core-shell bead
      structures.
AB  - Ultralong coaxial Au@Pt nanocables prepared by one-pot synthesis exhibit
      excellent electrocatalytic activity due to structural features of (1) numerous
      twinning boundaries and (2) lattice mismatch between the core and the shell. 

PMID- 24740140
TI  - To what extent do tutor-related behaviours influence student learning in PBL?
AB  - The purpose of this study was to investigate how tutor behaviours influence
      learning in problem-based learning (PBL). A previous study had indicated a
      significant influence of the tutor's social congruent behaviour on the PBL
      process and this study further investigates this finding by examining two groups
      of tutors displaying differences in social congruence. The participants were 77
      students under the tutelage of four tutors and a self-report questionnaire ranked
      two tutors to be more socially congruent as compared to the other two. Student
      learning was measured by a concept recall test and the results from the analysis
      of covariance indicated a significant impact of the tutor's social congruent
      behaviour on learning after the problem analysis phase but not on the self
      directed learning and reporting phases. It was concluded that the academic
      abilities of students and the small number of tutors involved may have affected
      the results, which led to the second part of this study. A group of 11 tutors
      were selected and the impact of their behaviours on student achievement measured
      by the module grade was examined. Results indicated that the tutor behaviours had
      a greater influence on average students as compared to the academically stronger
      and weaker students. This finding suggests that students who are academically
      stronger are not as reliant on the tutor while average students may depend more
      on the tutor to guide and motivate them in order to achieve the learning goals. 

PMID- 24740141
TI  - A high throughput single nucleotide polymorphism multiplex assay for parentage
      assignment in New Zealand sheep.
AB  - Accurate pedigree information is critical to animal breeding systems to ensure
      the highest rate of genetic gain and management of inbreeding. The abundance of
      available genomic data, together with development of high throughput genotyping
      platforms, means that single nucleotide polymorphisms (SNPs) are now the DNA
      marker of choice for genomic selection studies. Furthermore the superior
      qualities of SNPs compared to microsatellite markers allows for standardization
      between laboratories; a property that is crucial for developing an international
      set of markers for traceability studies. The objective of this study was to
      develop a high throughput SNP assay for use in the New Zealand sheep industry
      that gives accurate pedigree assignment and will allow a reduction in breeder
      input over lambing. This required two phases of development--firstly, a method of
      extracting quality DNA from ear-punch tissue performed in a high throughput cost
      efficient manner and secondly a SNP assay that has the ability to assign
      paternity to progeny resulting from mob mating. A likelihood based approach to
      infer paternity was used where sires with the highest LOD score (log of the ratio
      of the likelihood given parentage to likelihood given non-parentage) are
      assigned. An 84 "parentage SNP panel" was developed that assigned, on average,
      99% of progeny to a sire in a problem where there were 3,000 progeny from 120 mob
      mated sires that included numerous half sib sires. In only 6% of those cases was
      there another sire with at least a 0.02 probability of paternity. Furthermore dam
      information (either recorded, or by genotyping possible dams) was absent,
      highlighting the SNP test's suitability for paternity testing. Utilization of
      this parentage SNP assay will allow implementation of progeny testing into large
      commercial farms where the improved accuracy of sire assignment and genetic
      evaluations will increase genetic gain in the sheep industry.

PMID- 24740142
TI  - Geographic variation of melanisation patterns in a hornet species: genetic
      differences, climatic pressures or aposematic constraints?
AB  - Coloration of stinging insects is often based on contrasted patterns of light and
      black pigmentations as a warning signal to predators. However, in many social
      wasp species, geographic variation drastically modifies this signal through
      melanic polymorphism potentially driven by different selective pressures. To
      date, surprisingly little is known about the geographic variation of coloration
      of social wasps in relation to aposematism and melanism and to genetic and
      developmental constraints. The main objectives of this study are to improve the
      description of the colour variation within a social wasp species and to determine
      which factors are driving this variation. Therefore, we explored the evolutionary
      history of a polymorphic hornet, Vespa velutina Lepeletier, 1836, using
      mitochondrial and microsatellite markers, and we analysed its melanic variation
      using a colour space based on a description of body parts coloration. We found
      two main lineages within the species and confirmed the previous synonymy of V.
      auraria Smith, 1852, under V. velutina, differing only by the coloration. We also
      found that the melanic variation of most body parts was positively correlated,
      with some segments forming potential colour modules. Finally, we showed that the
      variation of coloration between populations was not related to their molecular,
      geographic or climatic differences. Our observations suggest that the coloration
      patterns of hornets and their geographic variations are determined by genes with
      an influence of developmental constraints. Our results also highlight that Vespa
      velutina populations have experienced several convergent evolutions of the
      coloration, more likely influenced by constraints on aposematism and Mullerian
      mimicry than by abiotic pressures on melanism. 

PMID- 24740143
TI  - Influence of vitamin E supplementation on glycaemic control: a meta-analysis of
      randomised controlled trials.
AB  - Observational studies have revealed that higher serum vitamin E concentrations
      and increased vitamin E intake and vitamin E supplementation are associated with
      beneficial effects on glycaemic control in type 2 diabetes mellitus (T2DM).
      However, whether vitamin E supplementation exerts a definitive effect on
      glycaemic control remains unclear. This article involves a meta-analysis of
      randomised controlled trials of vitamin E to better characterise its impact on
      HbA1c, fasting glucose and fasting insulin. PubMed, EMBASE and the Cochrane
      Library were electronically searched from the earliest possible date through
      April 2013 for all relevant studies. Weighted mean difference (WMD) was
      calculated for net changes using fixed-effects or random-effects models. Standard
      methods for assessing statistical heterogeneity and publication bias were used.
      Fourteen randomised controlled trials involving individual data on 714 subjects
      were collected in this meta-analysis. Increased vitamin E supplementation did not
      result in significant benefits in glycaemic control as measured by reductions in
      HbA1c, fasting glucose and fasting insulin. Subgroup analyses revealed a
      significant reduction in HbA1c (-0.58%, 95% CI -0.83 to -0.34) and fasting
      insulin (-9.0 pmol/l, 95% CI -15.90 to -2.10) compared with controls in patients
      with low baseline vitamin E status. Subgroup analyses also demonstrated that the
      outcomes may have been influenced by the vitamin E dosage, study duration, ethnic
      group, serum HbA1c concentration, and fasting glucose control status. In
      conclusion, there is currently insufficient evidence to support a potential
      beneficial effect of vitamin E supplementation on improvements of HbA1c and
      fasting glucose and insulin concentrations in subjects with T2DM. 

PMID- 24740144
TI  - Prospects of apicultural entrepreneurship in coastal districts of eastern India:
      a melissopalynological evaluation.
AB  - A melissopalynological analysis of fifty-one natural honey samples (twenty four
      spring, fifteen summer and twelve winter) collected during 2010-2011 from two
      east-coastal districts (20(0)20/ to 22(0)11/ N, 82(0)39/ to 87(0)01/ E) of
      Orissa, India was performed. Out of 37 unifloral samples found 25 were
      contributed by Apis cerana indica, seven by A. dorsata and the remaining five by
      A. florea. Out of 14 multifloral samples five were contributed by A. cerana
      indica, five by A. dorsata and the remaining four by A. florea. Principal
      component analysis confirmed the palynological classification of the unifloral
      honey samples. Eighty-two bee-plant taxa belonging to forty four families were
      recovered. The predominant nectariferous taxa of the spring season were Acanthus
      ilicifolius, Avicennia marina, Bruguiera gymnorrhiza, Cocos nucifera, Eucalyptus
      globulus, Phoenix paludosa, Pongamia pinnata, Prosopis juliflora, Sonneratia
      apetala and Syzygium cumini. In the summer the predominant nectariferous taxa
      were Borassus flabellifer, C. nucifera, E. globulus, Syzygium cumini, Terminalia
      arjuna, Aegiceras corniculatum, P. paludosa and Sonneratia apetala while those of
      the winter were Brassica nigra, Coriandrum sativum, Zizyphus jujuba, Alstonia
      scholaris, E. globulus and Bruguiera gymnorrhiza. Very low (<0.09) HDE/P for 98%
      of the samples and absence of toxic palynotaxa assure that these honeys are
      suitable for human consumption. Quite extended honey flow period with spring and
      summer as best forage seasons for the honeybees and occurrence of 82% of these
      honeys with APC Group II, III and IV justify the sustainability of the present
      study area for establishing moderate to large-scale apicultural entrepreneurship.
      This should improve the socio-economic status of the people of this region.

PMID- 24740146
TI  - A new morphological classification for the fibularis quartus muscle.
AB  - PURPOSE: The fibularis quartus muscle (FQ) is an accessory fibular muscle that
      can be found in humans, reportedly in up to 22%. The aim of this study was to
      classify morphological patterns of the FQ and its anatomical variations. METHODS:
      Eighty lower limbs of 40 formalin-fixed adult Korean cadavers were used in this
      study. RESULTS: The FQ was present in 13 of 80 specimens (16.3%). In two
      specimens, each specimen had two FQs with different origins and insertion sites.
      Thus, 15 cases of FQ were found in 13 specimens. The FQ originated from the
      fibularis brevis muscle (FB) in 12 cases (15%). In these cases, the FQ arose
      either as a muscle or as a tendon. The muscle fibers of the FQ merged into a
      tendon (8 of 12 cases) that inserted variously into (1) the tendon of the FB
      (three cases, 3.8%), (2) the lateral surface of calcaneus (two cases, 2.5%), (3)
      the inferior peroneal retinaculum (two cases, 2.5%), or (4) the dorsal surface of
      the base of fifth metatarsal bone (one case, 1.3%). The FQ arose as a tendon from
      the FB in 4 of 12 cases. In three of the four cases, the FQ inserted into the
      lateral surface of calcaneus. The FQ arose from structures other than the FB
      (three cases, 3.8%). CONCLUSION: The present study has demonstrated a new
      classification for the FQ and its anatomical variations, and provided detailed
      data for its accurate identification of a muscle and relevant surgical
      procedures.

PMID- 24740145
TI  - Erythroblastic islands in the bone marrow of patients with immune-related
      pancytopenia.
AB  - BACKGROUND: Immune-related pancytopenia (IRP) is characterized by pancytopenia
      caused by autoantibody-mediated bone marrow destruction or suppression. The bone
      marrows of IRP patients have remarkably increased erythroblastic islands (EIs).
      METHODOLOGY AND PRINCIPAL FINDINGS: We determined the immunoglobulin G (IgG)
      autoantibodies in some parts of EIs of IRP patients using immunofluorescence to
      investigate the biological function of EIs with IgG in the pathophysiology of
      IRP. The dominant class of autoantibodies detected in mononuclear cells was IgG
      (CD34 IgG, CD15 IgG, and GlycoA IgG), specifically IgG on GlycoA-positive cells
      (GlycoA IgG). Results show that extravascular hemolysis occurred in IRP through
      IgG autoantibodies in the EIs. These data included a high percentage of
      reticulocytes in the peripheral blood, hypererythrocytosis in the bone marrow,
      and high serum bilirubin. Furthermore, we examined the macrophages in the bone
      marrow of IRP patients. The results show that the number of activated macrophages
      relatively increased, and the phagocytic activity of macrophages significantly
      increased. CONCLUSIONS AND SIGNIFICANCE: Increased EIs with IgG were the sites of
      erythroblast phagocytosis by the activated macrophages, rather than
      erythropoietic niches. The IgG autoantibodies in the EIs possibly functioned as
      adhesion molecules for a ring of erythroblasts around the macrophages, thereby
      forming morphologic EIs.

PMID- 24740147
TI  - An accessory belly of the sternothyroid muscle on the anterior neck.
AB  - PURPOSE: Although anatomical variations were continuously found in the infrahyoid
      muscles, muscular variations of the sternothyroid muscle are still rare.
      MATERIALS AND METHODS: We found an accessory belly of the sternothyroid muscle in
      a 46-year-old Korean male cadaver during routine dissection course, whose cause
      of death was 'chronic renal failure'. RESULTS: The accessory belly attached to
      the oblique line of the lamina of the thyroid cartilage, covered the thyroid
      gland anteriorly, and attached to posterior surface of left sternothyroid muscle
      and pretracheal layer of the cervical fascia from side to side. It was supplied
      by the inferior thyroid artery from the left thyrocervical trunk and innervated
      by the nerve to sternothyroid muscle from the left ansa cervicalis. CONCLUSION:
      The present case is worth because it requires special attention performing
      procedures on the anterior neck.

PMID- 24740148
TI  - Molecular cloning and expression analysis of mannose receptor in blunt snout
      bream (Megalobrama amblycephala).
AB  - Mannose receptor (MR) plays a significant role in innate immune responses to
      pathogens in vertebrates. Here we characterized the first teleost MR from
      Megalobrama amblycephala, named maMR and its expression patterns were
      investigated. The full-length maMR consists of 5,295 bp encoding a putative
      protein of 1,433 amino acids. The predicted amino acid sequences showed that maMR
      contained a signal peptide, a cysteine-rich domain, a single fibronectin type II
      domain, eight tandemly arranged C-type lectin-like domains, a transmembrane
      domain and a C-terminal cytoplasmic domain. Phylogenetic analysis revealed the
      highest similarity of maMR with Danio rerio MR predicted by computational
      analysis. The maMR-mRNAs were ubiquitously transcribed in different tissues,
      However the highest transcripts were observed in head kidney. Transcripts of maMR
      significantly increased at the late stages of embryo and continued to be at the
      high levels after hatching. The maMR transcripts were significantly increased in
      M. amblycephala after stimulation with killed Aeromonas hydrophila.

PMID- 24740149
TI  - Mortality of inshore marine mammals in eastern Australia is predicted by
      freshwater discharge and air temperature.
AB  - Understanding environmental and climatic drivers of natural mortality of marine
      mammals is critical for managing populations effectively and for predicting
      responses to climate change. Here we use a 17-year dataset to demonstrate a clear
      relationship between environmental forcing and natural mortality of inshore
      marine mammals across a subtropical-tropical coastline spanning a latitudinal
      gradient of 13 degrees  (>2000 km of coastline). Peak mortality of inshore
      dolphins and dugongs followed sustained periods of elevated freshwater discharge
      (9 months) and low air temperature (3 months). At a regional scale, these results
      translated into a strong relationship between annual mortality and an index of El
      Nino-Southern Oscillation. The number of cyclones crossing the coastline had a
      comparatively weak effect on inshore marine mammal mortality, and only in the
      tropics. Natural mortality of offshore/migratory cetaceans was not predicted by
      freshwater discharge, but was related to lagged air temperature. These results
      represent the first quantitative link between environmental forcing and marine
      mammal mortality in the tropics, and form the basis of a predictive tool for
      managers to prepare responses to periods of elevated marine mammal mortality. 

PMID- 24740150
TI  - Gellan sulfate inhibits Plasmodium falciparum growth and invasion of red blood
      cells in vitro.
AB  - Here, we assessed the sulfated derivative of the microbial polysaccharide gellan
      gum and derivatives of lambda and kappa-carrageenans for their ability to inhibit
      Plasmodium falciparum 3D7 and Dd2 growth and invasion of red blood cells in
      vitro. Growth inhibition was assessed by means of flow cytometry after a 96-h
      exposure to the inhibitors and invasion inhibition was assessed by counting ring
      parasites after a 20-h exposure to them. Gellan sulfate strongly inhibited
      invasion and modestly inhibited growth for both P. falciparum 3D7 and Dd2; both
      inhibitory effects exceeded those achieved with native gellan gum. The hydrolyzed
      lambda-carrageenan and oversulfated kappa-carrageenan were less inhibitory than
      their native forms. In vitro cytotoxicity and anticoagulation assays performed to
      determine the suitability of the modified polysaccharides for in vivo studies
      showed that our synthesized gellan sulfate had low cytotoxicity and anticoagulant
      activity. 

PMID- 24740151
TI  - Laminoplasty and laminectomy hybrid decompression for the treatment of cervical
      spondylotic myelopathy with hypertrophic ligamentum flavum: a retrospective
      study.
AB  - OBJECTIVE: To report the outcomes of a posterior hybrid decompression protocol
      for the treatment of cervical spondylotic myelopathy (CSM) associated with
      hypertrophic ligamentum flavum (HLF). BACKGROUND: Laminoplasty is widely used in
      patients with CSM; however, for CSM patients with HLF, traditional laminoplasty
      does not include resection of a pathological ligamentum flavum. METHODS: This
      study retrospectively reviewed 116 CSM patients with HLF who underwent hybrid
      decompression with a minimum of 12 months of follow-up. The procedure consisted
      of reconstruction of the C4 and C6 laminae using CENTERPIECE plates with spinous
      process autografts, and resection of the C3, C5, and C7 laminae. Surgical
      outcomes were assessed using Japanese Orthopedic Association (JOA) score,
      recovery rate, cervical lordotic angle, cervical range of motion, spinal canal
      sagittal diameter, bone healing rates on both the hinge and open sides, dural sac
      expansion at the level of maximum compression, drift-back distance of the spinal
      cord, and postoperative neck pain assessed by visual analog scale. RESULTS: No
      hardware failure or restenosis was noted. Postoperative JOA score improved
      significantly, with a mean recovery rate of 65.3 +/- 15.5%. Mean cervical
      lordotic angle had decreased 4.9 degrees by 1 year after surgery (P<0.05).
      Preservation of cervical range of motion was satisfactory postoperatively. Bone
      healing rates 6 months after surgery were 100% on the hinge side and 92.2% on the
      open side. Satisfactory decompression was demonstrated by a significantly
      increased sagittal canal diameter and cross-sectional area of the dural sac
      together with a significant drift-back distance of the spinal cord. The dural sac
      was also adequately expanded at the time of the final follow-up visit.
      CONCLUSION: Hybrid laminectomy and autograft laminoplasty decompression using
      Centerpiece plates may facilitate bone healing and produce a comparatively
      satisfactory prognosis for CSM patients with HLF.

PMID- 24740152
TI  - Deletion of the complement C5a receptor alleviates the severity of acute
      pneumococcal otitis media following influenza A virus infection in mice.
AB  - There is considerable evidence that influenza A virus (IAV) promotes adherence,
      colonization, and superinfection by S. pneumoniae (Spn) and contributes to the
      pathogenesis of otitis media (OM). The complement system is a critical innate
      immune defense against both pathogens. To assess the role of the complement
      system in the host defense and the pathogenesis of acute pneumococcal OM
      following IAV infection, we employed a well-established transtympanically-induced
      mouse model of acute pneumococcal OM. We found that antecedent IAV infection
      enhanced the severity of acute pneumococcal OM. Mice deficient in complement C1qa
      (C1qa-/-) or factor B (Bf -/-) exhibited delayed viral and bacterial clearance
      from the middle ear and developed significant mucosal damage in the eustachian
      tube and middle ear. This indicates that both the classical and alternative
      complement pathways are critical for the oto-immune defense against acute
      pneumococcal OM following influenza infection. We also found that Spn increased
      complement activation following IAV infection. This was characterized by
      sustained increased levels of anaphylatoxins C3a and C5a in serum and middle ear
      lavage samples. In contrast, mice deficient in the complement C5a receptor (C5aR)
      demonstrated enhanced bacterial clearance and reduced severity of OM. Our data
      support the concept that C5a-C5aR interactions play a significant role in the
      pathogenesis of acute pneumococcal OM following IAV infection. It is possible
      that targeting the C5a-C5aR axis might prove useful in attenuating acute
      pneumococcal OM in patients with influenza infection. 

PMID- 24740153
TI  - Identification of a conserved non-protein-coding genomic element that plays an
      essential role in Alphabaculovirus pathogenesis.
AB  - Highly homologous sequences 154-157 bp in length grouped under the name of
      "conserved non-protein-coding element" (CNE) were revealed in all of the
      sequenced genomes of baculoviruses belonging to the genus Alphabaculovirus. A CNE
      alignment led to the detection of a set of highly conserved nucleotide clusters
      that occupy strictly conserved positions in the CNE sequence. The significant
      length of the CNE and conservation of both its length and cluster architecture
      were identified as a combination of characteristics that make this CNE different
      from known viral non-coding functional sequences. The essential role of the CNE
      in the Alphabaculovirus life cycle was demonstrated through the use of a CNE
      knockout Autographa californica multiple nucleopolyhedrovirus (AcMNPV) bacmid. It
      was shown that the essential function of the CNE was not mediated by the presumed
      expression activities of the protein- and non-protein-coding genes that overlap
      the AcMNPV CNE. On the basis of the presented data, the AcMNPV CNE was
      categorized as a complex-structured, polyfunctional genomic element involved in
      an essential DNA transaction that is associated with an undefined function of the
      baculovirus genome. 

PMID- 24740155
TI  - Urbanization level and woodland size are major drivers of woodpecker species
      richness and abundance.
AB  - Urbanization is a process globally responsible for loss of biodiversity and for
      biological homogenization. Urbanization may have a direct negative impact on
      species behaviour and indirect effects on species populations through alterations
      of their habitats, for example patch size and habitat quality. Woodpeckers are
      species potentially susceptible to urbanization. These birds are mostly forest
      specialists and the development of urban areas in former forests may be an
      important factor influencing their richness and abundance, but documented
      examples are rare. In this study we investigated how woodpeckers responded to
      changes in forest habitats as a consequence of urbanization, namely size and
      isolation of habitat patches, and other within-patch characteristics. We selected
      42 woodland patches in a gradient from a semi-natural rural landscape to the city
      centre of Poznan (Western Poland) in spring 2010. Both species richness and
      abundance of woodpeckers correlated positively to woodland patch area and
      negatively to increasing urbanization. Abundance of woodpeckers was also
      positively correlated with shrub cover and percentage of deciduous tree species.
      Furthermore, species richness and abundance of woodpeckers were highest at
      moderate values of canopy openness. Ordination analyses confirmed that
      urbanization level and woodland patch area were variables contributing most to
      species abundance in the woodpecker community. Similar results were obtained in
      presence-absence models for particular species. Thus, to sustain woodpecker
      species within cities it is important to keep woodland patches large, multi
      layered and rich in deciduous tree species. 

PMID- 24740154
TI  - Genome-wide association scan for variants associated with early-onset prostate
      cancer.
AB  - Prostate cancer is the most common non-skin cancer and the second leading cause
      of cancer related mortality for men in the United States. There is strong
      empirical and epidemiological evidence supporting a stronger role of genetics in
      early-onset prostate cancer. We performed a genome-wide association scan for
      early-onset prostate cancer. Novel aspects of this study include the focus on
      early-onset disease (defined as men with prostate cancer diagnosed before age 56
      years) and use of publically available control genotype data from previous genome
      wide association studies. We found genome-wide significant (p<5*10(-8)) evidence
      for variants at 8q24 and 11p15 and strong supportive evidence for a number of
      previously reported loci. We found little evidence for individual or systematic
      inflated association findings resulting from using public controls, demonstrating
      the utility of using public control data in large-scale genetic association
      studies of common variants. Taken together, these results demonstrate the
      importance of established common genetic variants for early-onset prostate cancer
      and the power of including early-onset prostate cancer cases in genetic
      association studies.

PMID- 24740157
TI  - Maternal prepregancy BMI and lipid profile during early pregnancy are
      independently associated with offspring's body composition at age 5-6 years: the
      ABCD study.
AB  - BACKGROUND: There is growing evidence that disturbances in maternal metabolism
      and, subsequently, intrauterine conditions affect foetal metabolism. Whether this
      has metabolic consequences in offspring later in life is not fully elucidated. We
      investigated whether maternal pre-pregnancy body mass index (pBMI) is associated
      with offspring's adiposity at age 5-6 years and whether this association is
      mediated by the mother's lipid profile during early pregnancy. METHODS: Data were
      derived from a multi-ethnic birth cohort, the Amsterdam Born Children and their
      Development (ABCD) study (inclusion 2003-2004). During early gestation mothers
      completed a questionnaire during pregnancy (pBMI) and random non-fasting blood
      samples were analysed for total cholesterol (TC), triglycerides (TG),
      apolipoprotein A1 (ApoA1), apolipoprotein B (ApoB) and total free fatty acids
      (FFA) in early gestation. At age 5-6 years, child's BMI, waist-to-height-ratio
      (WHtR) and fat% were assessed. RESULTS: Only non-diabetic mothers with at term
      born children were included (n = 1727). Of all women, 15.1% were overweight(BMI:
      25-29.9 kg/m2) and 4.3% were obese (BMI>=30 kg/m2). After adjustments for
      confounders, every unit increase in pBMI was linearly associated with various
      offspring variables: BMI (beta 0.10; 95% CI 0.08-0.12), WHtR*100 (beta 0.13; 95%
      CI 0.09-0.17), fat% (beta 0.21; 95% CI 0.13-0.29) and increased risk for
      overweight (OR:1.15; 95% CI 1.10-1.20). No convincing proof for mediation by
      maternal lipid profile during early gestation was found. Moreover, maternal FFA
      was associated with the child's fat percentage, BMI and risk for overweight.
      Maternal ApoB and TC were positively associated with the offspring's fat
      percentage and maternal TG was positively associated with their children's WHtR.
      CONCLUSIONS: Both pBMI and maternal lipids during early pregnancy are
      independently related to offspring adiposity.

PMID- 24740156
TI  - SNPs for parentage testing and traceability in globally diverse breeds of sheep.
AB  - DNA-based parentage determination accelerates genetic improvement in sheep by
      increasing pedigree accuracy. Single nucleotide polymorphism (SNP) markers can be
      used for determining parentage and to provide unique molecular identifiers for
      tracing sheep products to their source. However, the utility of a particular
      "parentage SNP" varies by breed depending on its minor allele frequency (MAF) and
      its sequence context. Our aims were to identify parentage SNPs with exceptional
      qualities for use in globally diverse breeds and to develop a subset for use in
      North American sheep. Starting with genotypes from 2,915 sheep and 74 breed
      groups provided by the International Sheep Genomics Consortium (ISGC), we
      analyzed 47,693 autosomal SNPs by multiple criteria and selected 163 with
      desirable properties for parentage testing. On average, each of the 163 SNPs was
      highly informative (MAF>=0.3) in 48+/-5 breed groups. Nearby polymorphisms that
      could otherwise confound genetic testing were identified by whole genome and
      Sanger sequencing of 166 sheep from 54 breed groups. A genetic test with 109 of
      the 163 parentage SNPs was developed for matrix-assisted laser
      desorption/ionization-time-of-flight mass spectrometry. The scoring rates and
      accuracies for these 109 SNPs were greater than 99% in a panel of North American
      sheep. In a blinded set of 96 families (sire, dam, and non-identical twin lambs),
      each parent of every lamb was identified without using the other parent's
      genotype. In 74 ISGC breed groups, the median estimates for probability of a
      coincidental match between two animals (PI), and the fraction of potential adults
      excluded from parentage (PE) were 1.1*10(-39) and 0.999987, respectively, for the
      109 SNPs combined. The availability of a well-characterized set of 163 parentage
      SNPs facilitates the development of high-throughput genetic technologies for
      implementing accurate and economical parentage testing and traceability in many
      of the world's sheep breeds. 

PMID- 24740158
TI  - The role of simulation in developing surgical skills.
AB  - Surgical training has followed the master-apprentice model for centuries but is
      currently undergoing a paradigm shift. The traditional model is inefficient with
      no guarantee of case mix, quality, or quantity. There is a growing focus on
      competency-based medical education in response to restrictions on doctors'
      working hours and the traditional mantra of "see one, do one, teach one" is being
      increasingly questioned. The medical profession is subject to more scrutiny than
      ever before and is facing mounting financial, clinical, and political pressures.
      Simulation may be a means of addressing these challenges. It provides a way for
      trainees to practice technical tasks in a protected environment without putting
      patients at risk and helps to shorten the learning curve. The evidence for
      simulation-based training in orthopedic surgery using synthetic models, cadavers,
      and virtual reality simulators is constantly developing, though further work is
      needed to ensure the transfer of skills to the operating theatre. 

PMID- 24740160
TI  - The chemistry of cationic polyphosphorus cages--syntheses, structure and
      reactivity.
AB  - The aim of this review is to provide a comprehensive view of the chemistry of
      cationic polyphosphorus cages. The synthetic protocols established for their
      preparation, which are all based on the functionalization of P4, and their
      intriguing follow-up chemistry are highlighted. In addition, this review intends
      to foster the interest of the inorganic, organic, catalytic and material oriented
      chemical communities in the versatile field of polyphosphorus cage compounds. In
      the long term, this is envisioned to contribute to the development of new
      synthetic procedures for the functionalization of P4 and its transformation into
      (organo-)phosphorus compounds and materials of added value. 

PMID- 24740161
TI  - A large-scale lithography-free metasurface with spectrally tunable super
      absorption.
AB  - Recently, periodically patterned metasurfaces have been employed to realize on
      chip super/near-perfect optical absorption. However, most reported meta-absorbers
      rely on top-down micro/nano-lithography, which imposed a serious cost barrier on
      the development of practical applications, especially in the visible-infrared
      (IR) domain and at very large scales. Here we report a simple method to
      manufacture super absorptive metasurfaces using direct sputtering deposition. By
      controlling the deposition and post thermal treatment conditions, random metallic
      nanoparticles (NPs) can be formed easily on rigid and flexible substrates to
      function as the nanoantennas of spectrally tunable meta-absorbers. This low-cost
      and highly scalable approach would release the manufacturing barrier for
      previously reported meta-absorbers and therefore enable the development of
      affordable and large-scale thin-film metamaterial structures and devices. 

PMID- 24740159
TI  - Sonic Hedgehog activation is implicated in diosgenin-induced megakaryocytic
      differentiation of human erythroleukemia cells.
AB  - Differentiation therapy is a means to treat cancer and is induced by different
      agents with low toxicity and more specificity than traditional ones. Diosgenin, a
      plant steroid, is able to induce megakaryocytic differentiation or apoptosis in
      human HEL erythroleukemia cells in a dose-dependent manner. However, the exact
      mechanism by which diosgenin induces megakaryocytic differentiation has not been
      elucidated. In this study, we studied the involvement of Sonic Hedgehog in
      megakaryocytic differentiation induced by diosgenin in HEL cells. First, we
      showed that different elements of the Hedgehog pathway are expressed in our model
      by qRT-PCR. Then, we focused our interest on key elements in the Sonic Hedgehog
      pathway: Smoothened receptor, GLI transcription factor and the ligand Sonic
      Hedgehog. We showed that Smoothened and Sonic Hedgehog were overexpressed in
      disogenin-treated cells and that GLI transcription factors were activated. Then,
      we showed that SMO inhibition using siSMO or the GLI antagonist GANT-61, blocked
      megakaryocytic differentiation induced by diosgenin in HEL cells. Furthermore, we
      demonstrated that Sonic Hedgehog pathway inhibition led to inhibition of ERK1/2
      activation, a major physiological pathway involved in megakaryocytic
      differentiation. In conclusion, our study reports, for the first time, a crucial
      role for the Sonic Hedgehog pathway in diosgenin-induced megakaryocytic
      differentiation in HEL cells. 

PMID- 24740162
TI  - The lethal fungus Batrachochytrium dendrobatidis is present in lowland tropical
      forests of far eastern Panama.
AB  - The fungal disease chytridiomycosis, caused by Batrachochytrium dendrobatidis
      (Bd), is one of the main causes of amphibian population declines and extinctions
      all over the world. In the Neotropics, this fungal disease has caused
      catastrophic declines in the highlands as it has spread throughout Central
      America down to Panama. In this study, we determined the prevalence and intensity
      of Bd infection in three species of frogs in one highland and four lowland
      tropical forests, including two lowland regions in eastern Panama in which the
      pathogen had not been detected previously. Bd was present in all the sites
      sampled with a prevalence ranging from 15-34%, similar to other Neotropical
      lowland sites. The intensity of Bd infection on individual frogs was low, ranging
      from average values of 0.11-24 zoospore equivalents per site. Our work indicates
      that Bd is present in anuran communities in lowland Panama, including the Darien
      province, and that the intensity of the infection may vary among species from
      different habitats and with different life histories. The population-level
      consequences of Bd infection in amphibian communities from the lowlands remain to
      be determined. Detailed studies of amphibian species from the lowlands will be
      essential to determine the reason why these species are persisting despite the
      presence of the pathogen. 

PMID- 24740163
TI  - Somatostatin receptor based PET/CT imaging with 68Ga-DOTA-Nal3-octreotide for
      localization of clinically and biochemically suspected insulinoma.
AB  - BACKGROUND: Localization of primary tumor in insulinoma is often difficult. We
      evaluated the role of 68Ga-DOTA-Nal3-Octreotide (DOTANOC) PET/CT for localization
      of primary tumor in patients with clinical and biochemical suspicion of
      insulinoma. METHODS: Data of 35 patients (age: 38.4+/-16.5 years) who underwent
      68Ga-DOTANOC PET/CT for clinical and biochemical suspicion of insulinoma
      (hypoglycemia, raised serum insulin and C-peptide levels) were retrospectively
      analyzed. PET/CT images were evaluated visually and semiquantitatively (SUV) by
      two experienced nuclear medicine physicians. A definite lesion in pancreas on non
      contrast CT showing increased 68Ga-DOTANOC was taken as positive. In the absence
      of CT lesion focal 68Ga-DOTANOC uptake in the pancreas more than liver was taken
      as positive. All patients had also undergone conventional imaging (CIM)
      (CT/MRI/endosonography) and their reports were retrieved for comparison.
      Histopathology and/or imaging/clinical/biochemical follow up (minimum 6 months)
      was used as reference standard. RESULTS: The mean serum insulin levels was 51.6+/
      54 uIU/mL and C-peptide level was 6.9+/-7.3 ng/mL. 68Ga-DOTANOC PET/CT was
      interpreted as positive in 11 patients (31.5%) and negative in 24 (68.5%). PET/CT
      demonstrated total 16 pancreatic lesions in 11 patients. In two patients it also
      showed both liver and lymph nodal metastases. 68Ga-DOTANOC PET/CT was true
      positive in 8, true negative in 1, false positive in 3 and false negative in 23
      patients. Per patient based sensitivity of PET/CT was 25.8% (95% CI: 11.8-44.6),
      specificity was 25% (95% CI: 0.6-80.5) and accuracy was 25.7%. The mean SUVmax of
      pancreatic lesions was 13.8+/-11.1. On comparison no significant difference was
      seen between CIM and PET/CT on patient based (P=1.00) or lesion based comparison
      (P=0.790). CONCLUSION: 68Ga-DOTANOC PET/CT has limited utility for localizing the
      primary tumor in patients with clinical and biochemical suspicion of insulinoma.
      However, it might be useful for differentiating benign and malignant insulinoma.
      Further prospective comparative studies are warranted.

PMID- 24740164
TI  - PSGL-1 and E/P-selectins are essential for T-cell rolling in inflamed CNS
      microvessels but dispensable for initiation of EAE.
AB  - T-cell migration across the blood-brain barrier is a crucial step in the
      pathogenesis of EAE, an animal model for MS. Live cell imaging studies
      demonstrated that P-selectin glycoprotein ligand-1 (PSGL-1) and its endothelial
      ligands E- and P-selectin mediate the initial rolling of T cells in brain vessels
      during EAE. As functional absence of PSGL-1 or E/P-selectins does not result in
      ameliorated EAE, we speculated that T-cell entry into the spinal cord is
      independent of PSGL-1 and E/P-selectin. Performing intravital microscopy, we
      observed the interaction of WT or PSGL-1(-/-) proteolipid protein-specific T
      cells in inflamed spinal cord microvessels of WT or E/P-selectin(-/-) SJL/J mice
      during EAE. T-cell rolling but not T-cell capture was completely abrogated in the
      absence of either PSGL-1 or E- and P-selectin, resulting in a significantly
      reduced number of T cells able to firmly adhere in the inflamed spinal cord
      microvessels, but did not lead to reduced T-cell invasion into the CNS
      parenchyma. Thus, PSGL-1 interaction with E/P-selectin is essential for T-cell
      rolling in inflamed spinal cord microvessels during EAE. Taken together with
      previous observations, our findings show that T-cell rolling is not required for
      successful T-cell entry into the CNS and initiation of EAE. 

PMID- 24740165
TI  - Rural-Urban Differences in Access to Specialist Providers of Colorectal Cancer
      Care in the United States: A Physician Workforce Issue.
AB  - IMPORTANCE: Although early detection and treatment of colorectal cancer has been
      shown to improve outcomes, geographic proximity may influence access to these
      services. OBJECTIVE: To examine the disparities that may exist in colorectal
      cancer screening and treatment by comparing the distribution of providers of
      these services in rural and urban counties in the United States. DESIGN, SETTING,
      AND PARTICIPANTS: A retrospective population-based study using data obtained from
      the 2009 Area Resource File for the entire US population within each county. MAIN
      OUTCOMES AND MEASURES: Counties in the United States were categorized as rural or
      urban using rural-urban continuum codes as our primary exposure. The proportion
      of gastroenterologists, general surgeons, and radiation oncologists per 100,000
      people in each county was estimated as primary outcomes. Multivariate linear
      regression analysis adjusted for county-level socioeconomic variables, such as
      percentages of females, blacks, population without insurance, those with a high
      school diploma, and median household income, to estimate the relative density of
      each category of these providers between urban and rural counties. RESULTS: In
      total, 3220 counties were identified, comprising 1807 rural and 1413 urban
      counties. An unadjusted analysis showed an increased density of
      gastroenterologists, general surgeons, and radiation oncologists per 100,000
      people in urban vs rural counties. A multivariable analysis revealed a
      significantly higher density of gastroenterologists (1.63; 95% CI, 1.40-1.85; P <
      .001), general surgeons (2.01; 95% CI, 1.28-2.73; P < .001), and radiation
      oncologists (0.68; 95% CI, 0.59-0.77; P < .001) per 100,000 people living in
      urban vs rural counties. CONCLUSIONS AND RELEVANCE: A rural-urban disparity
      exists in the density of gastroenterologists, general surgeons, and radiation
      oncologists who traditionally provide colorectal cancer screening services and
      treatment. This might affect access to these services and may negatively
      influence outcomes for colorectal cancer in rural areas.

PMID- 24740166
TI  - Prenatal calcium and vitamin D intake, and bone mass in later life.
AB  - The aging population will result in an increasing burden of osteoporotic
      fractures, necessitating the identification of novel strategies for prevention.
      There is increasing recognition that factors in utero may influence bone mineral
      accrual, and, thus, osteoporosis risk. The role of calcium and vitamin D has
      received much attention in recent years, and in this review, we will survey
      available studies relating maternal calcium and vitamin D status during pregnancy
      to offspring bone development. The evidence base supporting a positive influence
      on intrauterine skeletal growth appears somewhat stronger for maternal 25(OH)
      vitamin D concentration than for calcium intake, and the available data point
      toward the need for high-quality randomized controlled trials in order to inform
      public health policy. It is only with such a rigorous approach that it will be
      possible to delineate the optimal strategy for vitamin D supplementation in
      pregnancy in relation to offspring bone health. 

PMID- 24740167
TI  - Phenotypic and molecular characterization of multidrug resistant Klebsiella
      pneumoniae isolated from a university teaching hospital, China.
AB  - The multidrug-resistant rate of Klebsiella pneumoniae has risen rapidly
      worldwide. To better understand the multidrug resistance situation and molecular
      characterization of Klebsiella pneumoniae, a total of 153 Klebsiella pneumoniae
      isolates were collected, and drug susceptibility test was performed to detect its
      susceptibility patterns to 13 kinds of antibiotics. Phenotypic tests for
      carbapenemases ESBLs and AmpC enzyme-producing strains were performed to detect
      the resistance phenotype of the isolates. Then PCR amplification and sequencing
      analysis were performed for the drug resistance determinants. The results showed
      that 63 strains harbored bla CTX-M gene, and 14 strains harbored bla DHA gene.
      Moreover, there were 5 strains carrying bla KPC gene, among which 4 strains
      carried bla CTX-M, bla DHA and bla KPC genes, and these 4 strains were also
      resistant to imipenem. Our data indicated that drug-resistant Klebsiella
      pneumoniae were highly prevalent in the hospital. Thus it is warranted that
      surveillance of epidemiology of those resistant isolates should be a cause for
      concern, and appropriate drugs should be chosen.

PMID- 24740169
TI  - Multi-probe real-time PCR identification of four common Candida species in blood
      culture broth.
AB  - We developed a single-tube real-time polymerase chain reaction (PCR) assay with
      multiple hybridization probes for detecting Candida albicans, C. tropicalis, C.
      glabrata, and C. parapsilosis. Primers were designed to amplify 18S rRNA gene of
      the genus Candida, and DNA probes were designed to hybridize two areas of the
      amplicons. The amplification curves and specific melting peaks of the probes
      hybridized with PCR product were used for definite species identifications. The
      reaction specificity was 100 % when evaluating the assay using DNA samples from
      21 isolates of fungal and bacterial species. The assay was further evaluated in
      129 fungal blood culture broth samples which were culture positive for fungus. Of
      the 129 samples, 119 were positively identified as: C. albicans (39), C.
      tropicalis (30), C. parapsilosis (23), C. glabrata (20), Candida spp. (5), and
      two samples containing mixed C. glabrata/C. albicans and C. glabrata/C.
      tropicalis. The five Candida spp. were identified by sequencing analysis as C.
      krusei, C. dubliniensis, C. aquaetextoris, and two isolates of C. athensensis. Of
      the ten samples which showed negative PCR results, six were Cryptococcus
      neoformans, and the others were Trichosporon sp., Rhodotorula sp., Fusarium sp.,
      and Penicillium marneffei. Our findings show that the assay was highly effective
      in identifying the four medically important Candida species. The results can be
      available within 3 h after positivity of a blood culture broth sample. 

PMID- 24740168
TI  - Plasma cells in immunopathology: concepts and therapeutic strategies.
AB  - Plasma cells are terminally differentiated B cells that secrete antibodies,
      important for immune protection, but also contribute to any allergic and
      autoimmune disease. There is increasing evidence that plasma cell populations
      exhibit a considerable degree of heterogeneity with respect to their
      immunophenotype, migration behavior, lifetime, and susceptibility to
      immunosuppressive drugs. Pathogenic long-lived plasma cells are refractory to
      existing therapies. In contrast, short-lived plasma cells can be depleted by
      steroids and cytostatic drugs. Therefore, long-lived plasma cells are responsible
      for therapy-resistant autoantibodies and resemble a challenge for the therapy of
      antibody-mediated autoimmune diseases. Both lifetime and therapy resistance of
      plasma cells are supported by factors produced within their microenviromental
      niches. Current results suggest that plasma cell differentiation and survival
      factors such as IL-6 also signal via mammalian miRNAs within the plasma cell to
      modulate downstream transcription factors. Recent evidence also suggests that
      plasma cells and/or their immediate precursors (plasmablasts) can produce
      important cytokines and act as antigen-presenting cells, exhibiting so far
      underestimated roles in immune regulation and bone homeostasis. Here, we provide
      an overview on plasma cell biology and discuss exciting, experimental, and
      potential therapeutic approaches to eliminate pathogenic plasma cells. 

PMID- 24740170
TI  - Intravitreal aflibercept (Eylea((r))): a review of its use in patients with
      macular oedema secondary to central retinal vein occlusion.
AB  - Aflibercept is a fully human, recombinant fusion protein that acts as a soluble
      decoy receptor for vascular endothelial growth factor (VEGF) family members,
      including VEGF-A, VEGF-B and placental growth factor (P1GF), thereby inhibiting
      downstream signalling mediated by these ligands. Aflibercept binds all isoforms
      of VEGF-A with high affinity, and a markedly higher affinity than that of
      ranibizumab or bevacizumab. A formulation of aflibercept developed specifically
      for intravitreal injection (Eylea((r))) is approved for use in several countries
      for the treatment of patients with macular oedema secondary to central retinal
      vein occlusion (CRVO). In clinical trials (GALILEO and COPERNICUS) in patients
      with this condition, intravitreal aflibercept 2 mg every month improved best
      corrected visual acuity (BCVA), as measured by the proportion of study eyes with
      a gain of >=15 Early Treatment Diabetic Retinopathy Study letters from baseline,
      significantly more than sham injections at week 24 (primary analysis). The
      significant improvements achieved with intravitreal aflibercept compared with
      sham in the first 6 months were maintained in the second 6 months with as-needed
      (prn) dosing and monthly monitoring. Continued prn dosing with a reduced
      monitoring frequency was associated with decreased improvements. More data are
      needed to confirm the optimal monitoring frequency for use with prn dosing,
      subsequent to initial monthly injections, in order to maintain long-term
      efficacy. Intravitreal aflibercept was generally well tolerated in clinical
      trials and there is little potential for systemic drug accumulation. Thus,
      intravitreal aflibercept is an effective and generally well tolerated agent that
      extends the options available for the treatment of macular oedema secondary to
      CRVO.

PMID- 24740171
TI  - Controllable synthesis of porous Fe3O4@ZnO sphere decorated graphene for
      extraordinary electromagnetic wave absorption.
AB  - For the first time, mesoporous Fe3O4@ZnO sphere decorated graphene (GN
      pFe3O4@ZnO) composites with uniform size, considerable porosity, high
      magnetization and extraordinary electromagnetic (EM) wave absorption properties
      were synthesized by a simple and efficient three-step method. Structure and
      morphology details were characterized by X-ray diffraction, transmission electron
      microscopy, high-resolution electron microscopy and field-emission scanning
      electron microscopy. Electron microscopy images reveal that pFe3O4@ZnO spheres
      with obvious porous and core-shell structures are uniformly coated on both sides
      of the GN sheets without significant numbers of vacancies or apparent
      aggregation. EM wave absorption properties of epoxy containing 30 wt% GN
      pFe3O4@ZnO were investigated at room temperature in the frequency region of 0.2
      18 GHz. The absorption bandwidth with reflection loss (RL) values less than -10
      dB is up to 11.4 GHz, and the minimal RL is almost -40 dB. The intrinsic physical
      and chemical properties of the materials, the synergy of Fe3O4 and ZnO, and
      particularly the unique multi-interfaces are fundamental to the enhancement of EM
      absorption properties. The as-prepared GN-pFe3O4@ZnO composites are shown to be
      lightweight, have strong absorption, and broad frequency bandwidth EM absorbers. 

PMID- 24740172
TI  - Towards simultaneous measurements of electronic and structural properties in
      ultra-fast x-ray free electron laser absorption spectroscopy experiments.
AB  - The rapidly growing ultrafast science with X-ray lasers unveils atomic scale
      processes with unprecedented time resolution bringing the so called "molecular
      movie" within reach. X-ray absorption spectroscopy is one of the most powerful x
      ray techniques providing both local atomic order and electronic structure when
      coupled with ad-hoc theory. Collecting absorption spectra within few x-ray pulses
      is possible only in a dispersive setup. We demonstrate ultrafast time-resolved
      measurements of the LIII-edge x-ray absorption near-edge spectra of irreversibly
      laser excited Molybdenum using an average of only few x-ray pulses with a signal
      to noise ratio limited only by the saturation level of the detector. The
      simplicity of the experimental set-up makes this technique versatile and
      applicable for a wide range of pump-probe experiments, particularly in the case
      of non-reversible processes. 

PMID- 24740173
TI  - Lower obesity rate during residence at high altitude among a military population
      with frequent migration: a quasi experimental model for investigating spatial
      causation.
AB  - We sought to evaluate whether residence at high altitude is associated with the
      development of obesity among those at increased risk of becoming obese. Obesity,
      a leading global health priority, is often refractory to care. A potentially
      novel intervention is hypoxia, which has demonstrated positive long-term
      metabolic effects in rats. Whether or not high altitude residence confers benefit
      in humans, however, remains unknown. Using a quasi-experimental, retrospective
      study design, we observed all outpatient medical encounters for overweight active
      component enlisted service members in the U.S. Army or Air Force from January
      2006 to December 2012 who were stationed in the United States. We compared high
      altitude (>1.96 kilometers above sea level) duty assignment with low altitude
      (<0.98 kilometers). The outcome of interest was obesity related ICD-9 codes
      (278.00-01, V85.3x-V85.54) by Cox regression. We found service members had a
      lower hazard ratio (HR) of incident obesity diagnosis if stationed at high
      altitude as compared to low altitude (HR 0.59, 95% confidence interval [CI] 0.54
      0.65; p<0.001). Using geographic distribution of obesity prevalence among
      civilians throughout the U.S. as a covariate (as measured by the Centers for
      Disease Control and Prevention and the REGARDS study) also predicted obesity
      onset among service members. In conclusion, high altitude residence predicts
      lower rates of new obesity diagnoses among overweight service members in the U.S.
      Army and Air Force. Future studies should assign exposure using randomization,
      clarify the mechanism(s) of this relationship, and assess the net balance of
      harms and benefits of high altitude on obesity prevention. 

PMID- 24740174
TI  - Neighborhood sociodemographic predictors of Serious Emotional Disturbance (SED)
      in schools: demonstrating a small area estimation method in the National
      Comorbidity Survey (NCS-A) Adolescent Supplement.
AB  - We evaluate the precision of a model estimating school prevalence of SED using a
      small area estimation method based on readily-available predictors from area
      level census block data and school principal questionnaires. Adolescents at 314
      schools participated in the National Comorbidity Supplement, a national survey of
      DSM-IV disorders among adolescents. A multilevel model indicated that predictors
      accounted for under half of the variance in school-level SED and even less when
      considering block-group predictors or principal report alone. While Census
      measures and principal questionnaires are significant predictors of individual
      level SED, associations are too weak to generate precise school-level predictions
      of SED prevalence. 

PMID- 24740175
TI  - Measures for Predictors of Innovation Adoption.
AB  - Building on a narrative synthesis of adoption theories by Wisdom et al. (2013),
      this review identifies 118 measures associated with the 27 adoption predictors in
      the synthesis. The distribution of measures is uneven across the predictors and
      predictors vary in modifiability. Multiple dimensions and definitions of
      predictors further complicate measurement efforts. For state policymakers and
      researchers, more effective and integrated measurement can advance the adoption
      of complex innovations such as evidence-based practices. 

PMID- 24740176
TI  - [Systemic therapy and hyperthermia for locally advanced soft tissue sarcoma].
AB  - Patients with high-risk soft tissue sarcomas (FNCLCC grades 2-3, > 5 cm and deep
      lying) are at a high risk of local recurrence or distant metastases despite
      optimal surgical tumor resection. Therefore, multimodal treatment should be
      considered for this difficult to treat patient group. Besides surgery, radiation
      therapy and chemotherapy, hyperthermia has become a valid, complementary
      treatment option within multimodal treatment concepts. Hyperthermia in this
      context means the selective heating of the tumor region to temperatures of 40-43 
      degrees C for 60 min by microwave radiation in addition to simultaneous
      chemotherapy or radiation therapy. A randomized phase III study demonstrated that
      the addition of hyperthermia to neoadjuvant chemotherapy improved tumor response
      and was associated with a minimal risk of early disease progression as compared
      to chemotherapy alone. The addition of hyperthermia to a multimodal treatment
      regimen for high-risk soft tissue sarcoma consisting of surgery, radiation
      therapy and chemotherapy, either in the neoadjuvant or adjuvant setting after
      incomplete or marginal tumor resection, significantly improved local progression
      free and disease-free survival. Based on these results and due to the generally
      good tolerability of hyperthermia, this treatment method in combination with
      chemotherapy should be considered as a standard treatment option within
      multimodal treatment approaches for locally advanced high-risk soft tissue
      sarcoma. 

PMID- 24740177
TI  - [Improved survival rate for advanced distal gastric cancer. D2 gastrectomy with
      additional dissection of lymph nodes on the superior mesenteric artery (14v)].

PMID- 24740179
TI  - Sampling plant diversity and rarity at landscape scales: importance of sampling
      time in species detectability.
AB  - Documenting and estimating species richness at regional or landscape scales has
      been a major emphasis for conservation efforts, as well as for the development
      and testing of evolutionary and ecological theory. Rarely, however, are sampling
      efforts assessed on how they affect detection and estimates of species richness
      and rarity. In this study, vascular plant richness was sampled in 356 quarter
      hectare time-unlimited survey plots in the boreal region of northeast Alberta.
      These surveys consisted of 15,856 observations of 499 vascular plant species (97
      considered to be regionally rare) collected by 12 observers over a 2 year period.
      Average survey time for each quarter-hectare plot was 82 minutes, ranging from 20
      to 194 minutes, with a positive relationship between total survey time and total
      plant richness. When survey time was limited to a 20-minute search, as in other
      Alberta biodiversity methods, 61 species were missed. Extending the survey time
      to 60 minutes, reduced the number of missed species to 20, while a 90-minute cut
      off time resulted in the loss of 8 species. When surveys were separated by
      habitat type, 60 minutes of search effort sampled nearly 90% of total observed
      richness for all habitats. Relative to rare species, time-unlimited surveys had ~
      65% higher rare plant detections post-20 minutes than during the first 20 minutes
      of the survey. Although exhaustive sampling was attempted, observer bias was
      noted among observers when a subsample of plots was re-surveyed by different
      observers. Our findings suggest that sampling time, combined with sample size and
      observer effects, should be considered in landscape-scale plant biodiversity
      surveys.

PMID- 24740178
TI  - Feasibility and safety of a reduced duration of therapy of colony-stimulating
      factor in a dose-dense regimen.
AB  - PURPOSE: The risk of febrile neutropenia (FN) in cancer patients receiving
      chemotherapy is mainly due to the type of chemotherapy regimen and the presence
      of specific risk factors in patients. The recent trend of using a dose-dense
      treatment schedule has enhanced the risk of FN. In the present prospective study,
      we evaluated the feasibility of a reduction of duration of therapy with colony
      stimulating factor (G-CSF) in a dose-dense regimen. METHODS: Between June 2002
      and December 2011, 107 patients with a new diagnosis of non-Hodgkin lymphoma
      (NHL) receiving dose-dense chemotherapy, every 14 days, were included in the
      study. The primary endpoint was defined as the completion of planned chemotherapy
      cycles as scheduled. Secondary endpoints were median number of administered G-CSF
      doses (vials), incidence of FN, hospitalization and toxicity. RESULTS: The
      planned chemotherapy cycles (primary endpoint) were completed by 84.1 % of
      patients. The median number of G-CSF (lenograstim) doses administered for each
      patient was 24 (range 10-35), which corresponds to a median of five vials (range
      0-10) for each cycle. Grades 3-4 toxicities, related to G-CSF administration,
      included neutropenia and thrombocytopenia (14.0 and 1.9 %, respectively). No
      grades 3-4 bone pain was detected. The incidence of FN and hospitalization was
      9.3 % (10/107) and 4.5 % (5/107), respectively. CONCLUSIONS: Reduced dosage of G
      CSF allows dose-dense chemotherapy scheduling, limits exposure to G-CSF and also
      represents an opportunity for cost savings.

PMID- 24740180
TI  - Salmon, seabirds, and ecosystem dynamics.

PMID- 24740181
TI  - Domain within the helicase subunit Mcm4 integrates multiple kinase signals to
      control DNA replication initiation and fork progression.
AB  - Eukaryotic DNA synthesis initiates from multiple replication origins and
      progresses through bidirectional replication forks to ensure efficient
      duplication of the genome. Temporal control of initiation from origins and
      regulation of replication fork functions are important aspects for maintaining
      genome stability. Multiple kinase-signaling pathways are involved in these
      processes. The Dbf4-dependent Cdc7 kinase (DDK), cyclin-dependent kinase (CDK),
      and Mec1, the yeast Ataxia telangiectasia mutated/Ataxia telangiectasia mutated
      Rad3-related checkpoint regulator, all target the structurally disordered N
      terminal serine/threonine-rich domain (NSD) of mini-chromosome maintenance
      subunit 4 (Mcm4), a subunit of the mini-chromosome maintenance (MCM) replicative
      helicase complex. Using whole-genome replication profile analysis and single
      molecule DNA fiber analysis, we show that under replication stress the temporal
      pattern of origin activation and DNA replication fork progression are altered in
      cells with mutations within two separate segments of the Mcm4 NSD. The proximal
      segment of the NSD residing next to the DDK-docking domain mediates repression of
      late-origin firing by checkpoint signals because in its absence late origins
      become active despite an elevated DNA damage-checkpoint response. In contrast,
      the distal segment of the NSD at the N terminus plays no role in the temporal
      pattern of origin firing but has a strong influence on replication fork
      progression and on checkpoint signaling. Both fork progression and checkpoint
      response are regulated by the phosphorylation of the canonical CDK sites at the
      distal NSD. Together, our data suggest that the eukaryotic MCM helicase contains
      an intrinsic regulatory domain that integrates multiple signals to coordinate
      origin activation and replication fork progression under stress conditions. 

PMID- 24740182
TI  - Induction of multiciliated cells from induced pluripotent stem cells.

PMID- 24740184
TI  - Pan-ocular hemorrhage in thrombotic thrombocytopenic purpura.

PMID- 24740183
TI  - Should I stay or should I go? Dispersal and population structure in small,
      isolated desert populations of West African crocodiles.
AB  - The maintenance of both spatial and genetic connectivity is paramount to the long
      term persistence of small, isolated populations living in environments with
      extreme climates. We aim to identify the distribution of genetic diversity and
      assess population sub-structuring and dispersal across dwarfed desert populations
      of Crocodylus suchus, which occur in isolated groups, usually less than five
      individuals, along the mountains of Mauritania (West Africa). We used both
      invasive and non-invasive sampling methods and a combination of mitochondrial DNA
      (12 S and ND4) and microsatellite markers (32 loci and a subset of 12 loci). Our
      results showed high genetic differentiation and geographic structure in
      Mauritanian populations of C. suchus. We identified a metapopulation system
      acting within four river sub-basins (high gene flow and absence of genetic
      structure) and considerable genetic differentiation between sub-basins (FST
      range: 0.12-0.24) with rare dispersal events. Effective population sizes tend to
      be low within sub-basins while genetic diversity is maintained. Our study
      suggests that hydrographic networks (temporal connections along seasonal rivers
      during rainy periods) allow C. suchus to disperse and maintain metapopulation
      dynamics within sub-basins, which attenuate the loss of genetic diversity and the
      risk of extinction. We highlight the need of hydrographic conservation to protect
      vulnerable crocodiles isolated in small water bodies. We propose C. suchus as an
      umbrella species in Mauritania based on ecological affinities shared with other
      water-dependent species in desert environments. 

PMID- 24740185
TI  - Reduced promoter methylation and increased expression of CSPG4 negatively
      influences survival of HNSCC patients.
AB  - Proteoglycans are often overexpressed in tumors and can be found on several
      normal and neoplastic stem cells. In this study, we analyzed in-depth the role of
      CSPG4 in head and neck squamous cell carcinomas (HNSCC). Analysis of CSPG4 in a
      homogeneous study sample of HPV-negative stage IVa HNSCCs revealed overexpression
      of protein and mRNA levels in a subgroup of HNSCC tumors and a significant
      association of high CSPG4 protein levels with poor survival. This could be
      validated in three publicly available microarray datasets. As a potential cause
      for upregulated CSPG4 expression, we identified DNA hypomethylation in a CpG
      island of the promoter region. Accordingly, we found an inverse correlation of
      methylation and patient outcome. Finally, CSPG4 re-expression was achieved by
      demethylating treatment of highly methylated HNSCC cell lines establishing a
      direct link between methylation and CSPG4 expression. In conclusion, we
      identified CSPG4 as a novel biomarker in HNSCC on several biological levels and
      established a causative link between DNA methylation and CSPG4 protein and mRNA
      expression.

PMID- 24740186
TI  - PFOS induces behavioral alterations, including spontaneous hyperactivity that is
      corrected by dexamfetamine in zebrafish larvae.
AB  - Perfluorooctane sulfonate (PFOS) is a widely spread environmental contaminant. It
      accumulates in the brain and has potential neurotoxic effects. The exposure to
      PFOS has been associated with higher impulsivity and increased ADHD prevalence.
      We investigated the effects of developmental exposure to PFOS in zebrafish
      larvae, focusing on the modulation of activity by the dopaminergic system. We
      exposed zebrafish embryos to 0.1 or 1 mg/L PFOS (0.186 or 1.858 uM, respectively)
      and assessed swimming activity at 6 dpf. We analyzed the structure of spontaneous
      activity, the hyperactivity and the habituation during a brief dark period
      (visual motor response), and the vibrational startle response. The findings in
      zebrafish larvae were compared with historical data from 3 months old male mice
      exposed to 0.3 or 3 mg/kg/day PFOS throughout gestation. Finally, we investigated
      the effects of dexamfetamine on the alterations in spontaneous activity and
      startle response in zebrafish larvae. We found that zebrafish larvae exposed to
      0.1 mg/L PFOS habituate faster than controls during a dark pulse, while the
      larvae exposed to 1 mg/L PFOS display a disorganized pattern of spontaneous
      activity and persistent hyperactivity. Similarly, mice exposed to 0.3 mg/kg/day
      PFOS habituated faster than controls to a new environment, while mice exposed to
      3 mg/kg/day PFOS displayed more intense and disorganized spontaneous activity.
      Dexamfetamine partly corrected the hyperactive phenotype in zebrafish larvae. In
      conclusion, developmental exposure to PFOS in zebrafish induces spontaneous
      hyperactivity mediated by a dopaminergic deficit, which can be partially reversed
      by dexamfetamine in zebrafish larvae. 

PMID- 24740187
TI  - Recent highlights of ATVB: diabetes mellitus.

PMID- 24740188
TI  - All low-density lipoprotein particles are not created equal.

PMID- 24740189
TI  - Platelet GPIb-IX has suppressive effects on septic inflammation.

PMID- 24740190
TI  - New pathway for tissue-type plasminogen activator regulation.

PMID- 24740192
TI  - A technique for high-throughput protein crystallization in ionically cross-linked
      polysaccharide gel beads for X-ray diffraction experiments.
AB  - A simple technique for high-throughput protein crystallization in ionically cross
      linked polysaccharide gel beads has been developed for contactless handling of
      crystals in X-ray crystallography. The method is designed to reduce mechanical
      damage to crystals caused by physical contact between crystal and mount tool and
      by osmotic shock during various manipulations including cryoprotection, heavy
      atom derivatization, ligand soaking, and diffraction experiments. For this study,
      protein crystallization in alginate and kappa-carrageenan gel beads was performed
      using six test proteins, demonstrating that proteins could be successfully
      crystallized in gel beads. Two complete diffraction data sets from lysozyme and
      ID70067 protein crystals in gel beads were collected at 100 K without removing
      the crystals; the results showed that the crystals had low mosaicities. In
      addition, crystallization of glucose isomerase was carried out in alginate gel
      beads in the presence of synthetic zeolite molecular sieves (MS), a hetero
      epitaxic nucleant; the results demonstrated that MS can reduce excess nucleation
      of this protein in beads. To demonstrate heavy-atom derivatization, lysozyme
      crystals were successfully derivatized with K2PtBr6 within alginate gel beads.
      These results suggest that gel beads prevent serious damage to protein crystals
      during such experiments. 

PMID- 24740193
TI  - Colloidal assemblies of oriented maghemite nanocrystals and their NMR
      relaxometric properties.
AB  - An elevated-temperature polyol-based colloidal-chemistry approach allows for the
      development of size-tunable (50 and 86 nm) assemblies of maghemite iso-oriented
      nanocrystals, with enhanced magnetization. (1)H-nuclear magnetic resonance (NMR)
      relaxometric experiments show that the ferrimagnetic cluster-like colloidal
      entities exhibit a remarkable enhancement (4-5 times) in transverse relaxivity
      when compared to that of the superparamagnetic contrast agent Endorem(r), over an
      extended frequency range (1-60 MHz). The marked increase in the transverse
      relaxivity r2 at a clinical magnetic field strength (~1.41 T), which is 405.1 and
      508.3 mM(-1) s(-1) for small and large assemblies, respectively, makes it
      possible to relate the observed response to the raised intra-aggregate magnetic
      material volume fraction. Furthermore, cell tests with a murine fibroblast
      culture medium confirmed cell viability in the presence of the clusters. We
      discuss the NMR dispersion profiles on the basis of relaxivity models to
      highlight the magneto-structural characteristics of the materials for improved T2
      weighted magnetic resonance images. 

PMID- 24740194
TI  - The role of cytotoxic chemotherapy in the management of progressive glioblastoma
      : a systematic review and evidence-based clinical practice guideline.
AB  - QUESTION: What is the impact of cytotoxic chemotherapy on disease control and
      survival in the adult patient with progressive glioblastoma? TARGET POPULATION:
      This recommendation applies to adults patients with progressive glioblastoma.
      RECOMMENDATIONS  LEVEL II: Temozolomide is recommended as superior to
      procarbazine in patients with first relapse of glioblastoma after having received
      nitrosourea chemotherapy or no prior cytotoxic chemotherapy at the time of
      initial therapy. The use of BCNU-impregnated biodegradable polymer wafers is
      recommended in the management of progressive glioblastoma as a surgical adjunct
      when cytoreductive surgery is indicated, taking into account the associated
      toxicities seen with this modality. LEVEL III: Consideration of a variety of
      cytotoxic chemotherapy agents of uncertain benefit is recommended in the setting
      of progressive glioblastoma based on the judgment of the treating physician
      taking into account the individual patients prior treatment exposure, systemic
      health, and likelihood of tolerance of the toxicities of any given agent. It is
      recommended in such cases that enrollment in available clinical trials be
      encouraged.

PMID- 24740196
TI  - A phase 2 trial of verubulin for recurrent glioblastoma: a prospective study by
      the Brain Tumor Investigational Consortium (BTIC).
AB  - Treatment options are limited for recurrent glioblastoma (GBM). Verubulin is a
      microtubule destabilizer and vascular disrupting agent that achieve high brain
      concentration relative to plasma in animals. Adults with recurrent GBM who failed
      prior standard therapy were eligible. The primary endpoint was 1-month
      progression-free survival (PFS-1) for bevacizumab refractory (Group 2) and 6
      month progression-free survival (PFS-6) for bevacizumab naive patients (Group 1).
      Verubulin was administered at 3.3 mg/m(2) as a 2-h intravenous infusion once
      weekly for 3 consecutive weeks in a 4-week cycle. The planned sample size was 34
      subjects per cohort. 56 patients (37 men, 19 women) were enrolled, 31 in Group 1
      and 25 in Group 2. The PFS-6 for Group 1 was 14% and the PFS-1 for Group 2 was
      20%. Median survival from onset of treatment was 9.5 months in Group 1 and 3.4
      months in Group 2. Best overall response was partial response (n = 3; 10% in
      Group 1; n = 1; 4.2% in Group 2) and stable disease (n = 7; 23% in Group 1; n =
      5; 21% in Group 2). In Group 1, 38.7% of patients experienced a serious adverse
      event; however only 3.2% were potentially attributable to study drug. In Group 2,
      44% of patients experienced a serious adverse event although none were
      attributable to study drug. Accrual was terminated early for futility. Single
      agent verubulin, in this dose and schedule, is well tolerated, associated with
      moderate but tolerable toxicity but has limited activity in either bevacizumab
      naive or refractory recurrent GBM.

PMID- 24740195
TI  - The role of targeted therapies in the management of progressive glioblastoma : a
      systematic review and evidence-based clinical practice guideline.
AB  - QUESTION: What is the influence of targeted medical therapies on disease control
      and survival in the adult patient with progressive glioblastoma? TARGETED
      POPULATION: This recommendation applies to adult patients with progressive
      glioblastoma RECOMMENDATIONS: Level III Treatment with bevacizumab is recommended
      as it provides improved disease control compared to historical controls as
      measured by best imaging response and progression free survival at 6 months.
      Given that there are a large number of therapies are available for progressive
      glioblastoma that may be applied under selected circumstances dependent on
      patient characteristics and treating physician judgment, it is strongly
      recommended that patients with progressive glioblastoma be enrolled in properly
      designed clinical investigations to provide convincing evidence of therapeutic
      value.

PMID- 24740197
TI  - Decreased expression of LASS2 is associated with worse prognosis in meningiomas.
AB  - Homo sapiens longevity assurance homolog 2 of yeast LAG1 (LASS2) has been
      indicated to have a critical role in various tumors. In the study, we aimed to
      evaluate the LASS2 expression level in prognostic significance and compare it
      with commonly used biomarkers: Ki-67, p53 and progesterone receptor (PR) for
      patients with meningiomas. Firstly, 50 fresh tissues and 143 paraffin-embedded
      meningiomas samples were analyzed for LASS2 expression by quantitative PCR and
      immunohistochemistry (IHC), respectively. Subsequently, LASS2 immunostaining was
      evaluated for its clinical significance. Furthermore, Correlations of LASS2
      expression with common biomarkers were assessed. Both PCR and IHC results showed
      LASS2 was downregulated in high-grade meningiomas in comparison with that of
      grade I or normal brain (all P < 0.01). IHC results demonstrated LASS2 intensity
      distribution (ID) score was significantly correlated with tumor size, brain
      invasion, tumor recurrence and clinical course (all P < 0.01), whereas no
      correlation of LASS2 ID score with sex or Simpson grade. Moreover, lower LASS2 ID
      score was strikingly associated with shorter overall and progression-free
      survival (P < 0.01). Pearson's analysis revealed the ID score was significantly
      reversely associated with Ki-67 and p53 but not with PR. More
      importantly,multivariate analyses revealed that LASS2 was an independent
      prognostic factor (P < 0.05). To our knowledge, it is the first time to
      investigate the expression of LASS2 and identify it as a potential biomarker for
      prognosis in meningiomas.

PMID- 24740198
TI  - Dynamics of social behavior in fruit fly larvae.
AB  - We quantified the extent and dynamics of social interactions among fruit fly
      larvae over time. Both a wild-type laboratory population and a recently-caught
      strain of larvae spontaneously formed social foraging groups. Levels of
      aggregation initially increased during larval development and then declined with
      the wandering stage before pupation. We show that larvae aggregated more on hard
      than soft food, and more at sites where we had previously broken the surface of
      the food. Groups of larvae initiated burrowing sooner than solitary individuals,
      indicating that one potential benefit of larval aggregations is an improved
      ability to dig and burrow into the food substrate. We also show that two closely
      related species, D. melanogaster and D. simulans, differ in their tendency to
      aggregate, which may reflect different evolutionary histories. Our protocol for
      quantifying social behavior in larvae uncovered robust social aggregations in
      this simple model, which is highly amenable to neurogenetic analyses, and can
      serve for future research into the mechanisms and evolution of social behavior. 

PMID- 24740200
TI  - Financial strain and cancer risk behaviors among African Americans.
AB  - BACKGROUND: African Americans suffer disproportionately from the adverse
      consequences of behavioral risk factors for cancer relative to other ethnic
      groups. Recent studies have assessed how financial strain might uniquely
      contribute to engagement in modifiable behavioral risk factors for cancer, but
      not among African Americans. The current study examined associations between
      financial strain and modifiable cancer risk factors (smoking, at-risk alcohol
      use, overweight/obesity, insufficient physical activity, inadequate fruit and
      vegetable intake, and multiple risk factors) among 1,278 African American adults
      (age, 46.5 +/- 12.6 years; 77% female) and explored potential mediators (stress
      and depressive symptoms) of those associations. METHODS: Logistic regression
      models were used to examine associations between financial strain and cancer risk
      factors. Analyses were adjusted for age, sex, partner status, income, educational
      level, and employment status. Analyses involving overweight/obesity status
      additionally controlled for fruit and vegetable intake and physical activity.
      Nonparametric bootstrapping procedures were used to assess mediation. RESULTS:
      Greater financial strain was associated with greater odds of insufficient
      physical activity (P < 0.003) and smoking (P = 0.005) and was positively
      associated with the total number of cancer risk factors (P < 0.0001). There was a
      significant indirect effect of both stress and depressive symptoms on the
      relations of financial strain with physical inactivity and multiple risk factors,
      respectively. CONCLUSIONS: Future interventions aimed at reducing cancer
      disparities should focus on African Americans experiencing higher financial
      strain while addressing their stress and depressive symptoms. IMPACT:
      Longitudinal studies are needed to assess the temporal and causal relations
      between financial strain and modifiable behavioral cancer risk factors among
      African Americans.

PMID- 24740201
TI  - Maternal smoking and DNA methylation in newborns: in utero effect or epigenetic
      inheritance?
AB  - BACKGROUND: Maternal smoking in pregnancy is associated with adverse health
      outcomes in children, including cancers; underlying mechanisms may include
      epigenetic modifications. Using Illumina's 450K array, we previously identified
      differential DNA methylation related to maternal smoking during pregnancy at 26
      CpG sites (CpGs) in 10 genes in newborn cord bloods from the Norwegian Mother and
      Child Cohort Study (MoBa). Whether these methylation signals in newborns reflect
      in utero exposure only or possibly epigenetic inheritance of smoking-related
      modifications is unclear. METHODS: We therefore evaluated the impact of the
      timing of mother's smoking (before or during pregnancy using cotinine measured at
      18 weeks gestation), the father's smoking before conception, and the
      grandmother's smoking during her pregnancy with the mother on methylation at
      these 26 CpGs in 1,042 MoBa newborns. We used robust linear regression, adjusting
      for covariates, applying Bonferroni correction. RESULTS: The strongest and only
      statistically significant associations were observed for sustained smoking by the
      mother during pregnancy through at least gestational week 18 (P < 1.6 * 10(-5)
      for all 26 CpGs). We observed no statistically significant differential
      methylation due to smoking by the mother before pregnancy or that ceased by week
      18, father's smoking before conception, or grandmother's smoking while pregnant
      with the mother. CONCLUSIONS: Differential methylation at these CpGs in newborns
      seems to reflect sustained in utero exposure rather than epigenetic inheritance.
      IMPACT: Smoking cessation in early pregnancy may negate effects on methylation.
      Analyses of maternal smoking during pregnancy and offspring health outcomes,
      including cancer, limited to ever smoking might miss true associations. Cancer
      Epidemiol Biomarkers Prev; 23(6); 1007-17. (c)2014 AACR.

PMID- 24740202
TI  - A comparison of nicotine biomarkers and smoking patterns in daily and nondaily
      smokers.
AB  - BACKGROUND: Nondaily or intermittent smokers (ITS) are increasingly common, but
      how much nicotine, if any, ITS take in and how quickly they metabolize it has not
      yet been studied. METHODS: We compared carbon monoxide (CO), urinary cotinine,
      and nicotine metabolism [nicotine metabolite ratio (NMR): 3
      hydroxycotinine:cotinine] in 224 ITS and 222 daily smokers (DS). Effects of
      gender and ethnicity were examined. RESULTS: DS had higher cotinine
      concentrations than ITS (1,396 +/- 69 vs. 478 +/- 44 ng/mL), attributable to
      higher cigarettes per day (CPD). In both groups, cotinine rose more slowly as CPD
      increased. There were no differences in cotinine between White (WH) and African
      American (AA) DS; among ITS, AA cotinine was over twice that of WH. Among DS, CO
      was significantly higher among WH than AA smokers, but significantly lower among
      WH ITS than AA ITS. Although AA ITS smoked more than WH ITS (CPD: 4.13 +/- 0.55
      vs. 3.31 +/- 0.41), this did not account for the observed cotinine nor CO
      differences. There were no differences in NMR by group or race, nor any gender
      effects. CONCLUSIONS: At comparable CPD, DS' and ITS' intake of nicotine per
      cigarette was similar, as were their rates of nicotine metabolism. Among ITS, AA
      smokers smoke more and take in more nicotine per cigarette than WH ITS,
      consistent with the view of ITS as a heterogeneous group. IMPACT: Differences in
      nicotine intake per cigarette and metabolism likely cannot account for
      differences in DS and ITS smoking. Future studies should explore ethnic
      differences in ITS smoking.

PMID- 24740199
TI  - Variation in NF-kappaB signaling pathways and survival in invasive epithelial
      ovarian cancer.
AB  - Survival in epithelial ovarian cancer (EOC) is influenced by the host immune
      response, yet the key genetic determinants of inflammation and immunity that
      affect prognosis are not known. The nuclear factor-kappaB (NF-kappaB)
      transcription factor family plays an important role in many immune and
      inflammatory responses, including the response to cancer. We studied common
      inherited variation in 210 genes in the NF-kappaB family in 10,084 patients with
      invasive EOC (5,248 high-grade serous, 1,452 endometrioid, 795 clear cell, and
      661 mucinous) from the Ovarian Cancer Association Consortium. Associations
      between genotype and overall survival were assessed using Cox regression for all
      patients and by major histology, adjusting for known prognostic factors and
      correcting for multiple testing (threshold for statistical significance, P < 2.5
      * 10(-5)). Results were statistically significant when assessed for patients of a
      single histology. Key associations were with caspase recruitment domain family,
      member 11 (CARD11) rs41324349 in patients with mucinous EOC [HR, 1.82; 95%
      confidence interval (CI), 1.41-2.35; P = 4.13 * 10(-6)] and tumor necrosis factor
      receptor superfamily, member 13B (TNFRSF13B) rs7501462 in patients with
      endometrioid EOC (HR, 0.68; 95% CI, 0.56-0.82; P = 2.33 * 10(-5)). Other
      associations of note included TNF receptor-associated factor 2 (TRAF2) rs17250239
      in patients with high-grade serous EOC (HR, 0.84; 95% CI, 0.77-0.92; P = 6.49 *
      10(-5)) and phospholipase C, gamma 1 (PLCG1) rs11696662 in patients with clear
      cell EOC (HR, 0.43; 95% CI, 0.26-0.73; P = 4.56 * 10(-4)). These associations
      highlight the potential importance of genes associated with host inflammation and
      immunity in modulating clinical outcomes in distinct EOC histologies.

PMID- 24740203
TI  - Single-nucleotide polymorphisms in SLC22A23 are associated with ulcerative
      colitis in a Canadian white cohort.
AB  - BACKGROUND: SLC22A23 is an orphan gene in the SLC22 family of organic membrane
      transporters, and its single-nucleotide polymorphism rs17309827-T was recently
      nominally associated with intestinal inflammation in a genome-wide association
      study. Other polymorphisms in the SLC22A23 gene have been associated with
      diseases with an inflammatory component, and polymorphisms in related genes in
      the SLC22 family have been repeatedly associated with inflammatory bowel disease
      (IBD). OBJECTIVE: In a candidate-gene study using a well-phenotyped, highly
      monitored, Manitoban white cohort, we investigated whether variations in SLC22A23
      were associated with intestinal inflammation. DESIGN: Selected genetic variations
      were genotyped by using fluorescent-based assays or a polymerase chain reaction
      restriction fragment length polymorphism analysis in 160 individuals with Crohn
      disease, 149 individuals with ulcerative colitis, and 142 healthy control
      subjects to determine genetic associations. RESULTS: Homozygocity for single
      nucleotide polymorphisms rs4959235-TT and rs950318-GG was associated with IBD,
      whereby 6% of patients (18 of 311 cases) carried these genotypes, but they were
      not seen in healthy controls. CONCLUSION: Associations reported in this article
      add to the emerging evidence that SLC22A23 variants could modify IBD risk.
      However, the biology of the gene and impact of variations on the gene's functions
      need to be tested to validate a causative role.

PMID- 24740204
TI  - Rice consumption is not associated with risk of cardiovascular disease morbidity
      or mortality in Japanese men and women: a large population-based, prospective
      cohort study.
AB  - BACKGROUND: Rice consumption has been associated with risk of type 2 diabetes,
      but its relation with cardiovascular disease (CVD) is limited. OBJECTIVE: We
      examined the association between rice consumption and risk of CVD incidence and
      mortality in a Japanese population. DESIGN: This was a prospective study in
      91,223 Japanese men and women aged 40-69 y in whom rice consumption was
      determined and updated from 3 self-administered food-frequency questionnaires,
      each 5 y apart. Follow-up for incidence was from 1990 to 2009 in cohort I and
      1993 to 2007 in cohort II and for mortality was from 1990 to 2009 in cohort I and
      1993 to 2009 in cohort II. HRs and 95% CIs of CVD incidence and mortality were
      calculated according to quintiles of cumulative average rice consumption.
      RESULTS: In 15-18 y of follow-up, we ascertained 4395 incident cases of stroke,
      1088 incident cases of ischemic heart disease (IHD), and 2705 deaths from CVD.
      Rice consumption was not associated with risk of incident stroke or IHD; the
      multivariable HR (95% CI) in the highest compared with lowest rice consumption
      quintiles was 1.01 (0.90, 1.14) for total stroke and 1.08 (0.84, 1.38) for IHD.
      Similarly, there was no association between rice consumption and risk of
      mortality from CVD; the HR (95% CI) for mortality from total CVD was 0.97 (0.84,
      1.13). There were no interactions with sex or effect modifications by body mass
      index for any endpoint. CONCLUSION: Rice consumption is not associated with risk
      of CVD morbidity or mortality.

PMID- 24740205
TI  - Metabolomics in nutritional epidemiology: identifying metabolites associated with
      diet and quantifying their potential to uncover diet-disease relations in
      populations.
AB  - BACKGROUND: Metabolomics is an emerging field with the potential to advance
      nutritional epidemiology; however, it has not yet been applied to large cohort
      studies. OBJECTIVES: Our first aim was to identify metabolites that are
      biomarkers of usual dietary intake. Second, among serum metabolites correlated
      with diet, we evaluated metabolite reproducibility and required sample sizes to
      determine the potential for metabolomics in epidemiologic studies. DESIGN:
      Baseline serum from 502 participants in the Prostate, Lung, Colorectal, and
      Ovarian (PLCO) Cancer Screening Trial was analyzed by using ultra-high
      performance liquid-phase chromatography with tandem mass spectrometry and gas
      chromatography-mass spectrometry. Usual intakes of 36 dietary groups were
      estimated by using a food-frequency questionnaire. Dietary biomarkers were
      identified by using partial Pearson's correlations with Bonferroni correction for
      multiple comparisons. Intraclass correlation coefficients (ICCs) between samples
      collected 1 y apart in a subset of 30 individuals were calculated to evaluate
      intraindividual metabolite variability. RESULTS: We detected 412 known
      metabolites. Citrus, green vegetables, red meat, shellfish, fish, peanuts, rice,
      butter, coffee, beer, liquor, total alcohol, and multivitamins were each
      correlated with at least one metabolite (P < 1.093 * 10(-6); r = -0.312 to
      0.398); in total, 39 dietary biomarkers were identified. Some correlations
      (citrus intake with stachydrine) replicated previous studies; others, such as
      peanuts and tryptophan betaine, were novel findings. Other strong associations
      included coffee (with trigonelline-N-methylnicotinate and quinate) and alcohol
      (with ethyl glucuronide). Intraindividual variability in metabolite levels (1-y
      ICCs) ranged from 0.27 to 0.89. Large, but attainable, sample sizes are required
      to detect associations between metabolites and disease in epidemiologic studies,
      further emphasizing the usefulness of metabolomics in nutritional epidemiology.
      CONCLUSIONS: We identified dietary biomarkers by using metabolomics in an
      epidemiologic data set. Given the strength of the associations observed, we
      expect that some of these metabolites will be validated in future studies and
      later used as biomarkers in large cohorts to study diet-disease associations. The
      PLCO trial was registered at clinicaltrials.gov as NCT00002540.

PMID- 24740206
TI  - Added sugar intake in South Africa: findings from the Adult Prospective Urban and
      Rural Epidemiology cohort study.
AB  - BACKGROUND: Obesity and other noncommunicable disease (NCD) risk factors are
      increasing in low- and middle-income countries. There are few data on the
      association between increased added sugar intake and NCD risk in these countries.
      OBJECTIVE: We assessed the relation between added sugar intake and NCD risk
      factors in an African cohort study. Added sugars were defined as all
      monosaccharides and disaccharides added to foods and beverages during processing,
      cooking, and at the table. DESIGN: We conducted a 5-y follow-up of a cohort of
      2010 urban and rural men and women aged 30-70 y of age at recruitment in 2005
      from the North West Province in South Africa. RESULTS: Added sugar intake,
      particularly in rural areas, has increased rapidly in the past 5 y. In rural
      areas, the proportion of adults who consumed sucrose-sweetened beverages
      approximately doubled (for men, from 25% to 56%; for women, from 33% to 63%) in
      the past 5 y. After adjustment, subjects who consumed more added sugars (>=10%
      energy from added sugars) compared with those who consumed less added sugars had
      a higher waist circumference [mean difference (95% CI): 1.07 cm (0.35, 1.79 cm)]
      and body mass index (in kg/m2) [0.43 (0.12, 0.74)] and lower HDL cholesterol [
      0.08 mmol/L (-0.14, 0.002 mmol/L)]. CONCLUSIONS: This cohort showed dramatic
      increases in added sugars and sucrose-sweetened beverage consumption in both
      urban and rural areas. Increased consumption was associated with increased NCD
      risk factors. In addition, the study showed that the nutrition transition has
      reached a remote rural area in South Africa. Urgent action is needed to address
      these trends.

PMID- 24740207
TI  - Genome-wide association study of circulating vitamin D-binding protein.
AB  - BACKGROUND: Vitamin D status may influence a spectrum of health outcomes,
      including osteoporosis, arthritis, cardiovascular disease, and cancer. Vitamin D
      binding protein (DBP) is the primary carrier of vitamin D in the circulation and
      regulates the bioavailability of 25-hydroxyvitamin D. Epidemiologic studies have
      shown direct DBP-risk relations and modification by DBP of vitamin D-disease
      associations. OBJECTIVE: We aimed to characterize common genetic variants that
      influence the DBP biochemical phenotype. DESIGN: We conducted a genome-wide
      association study (GWAS) of 1380 men through linear regression of single
      nucleotide polymorphisms (SNPs) in the Illumina HumanHap500/550/610 array on
      fasting serum DBP, assuming an additive genetic model, with adjustment for age at
      blood collection. RESULTS: We identified 2 independent SNPs located in the gene
      encoding DBP, GC, that were highly associated with serum DBP: rs7041 (P = 1.42 *
      10-246) and rs705117 (P = 4.7 * 10-91). For both SNPs, mean serum DBP decreased
      with increasing copies of the minor allele: mean DBP concentrations (nmol/L) were
      7335, 5149, and 3152 for 0, 1, and 2 copies of rs7041 (T), respectively, and
      6339, 4280, and 2341, respectively, for rs705117 (G). DBP was also associated
      with rs12144344 (P = 5.9 * 10-7) in ST6GALNAC3. CONCLUSIONS: In this GWAS
      analysis, to our knowledge the first to examine this biochemical phenotype, 2
      variants in GC--one exonic and one intronic--were associated with serum DBP
      concentrations at the genome-wide level of significance. Understanding the
      genetic contributions to circulating DBP may provide greater insights into the
      vitamin D binding, transport, and other functions of DBP and the effect of
      vitamin D status on health outcomes.

PMID- 24740208
TI  - Dairy fat intake is associated with glucose tolerance, hepatic and systemic
      insulin sensitivity, and liver fat but not beta-cell function in humans.
AB  - BACKGROUND: Plasma phospholipid concentrations of trans-palmitoleic acid (trans
      16:1n-7), a biomarker of dairy fat intake, are inversely associated with incident
      type 2 diabetes in 2 US cohorts. OBJECTIVE: The objective was to investigate
      whether the intake of trans-16:1n-7 in particular, or dairy fat in general, is
      associated with glucose tolerance and key factors determining glucose tolerance.
      DESIGN: A cross-sectional investigation was undertaken in 17 men and women with
      nonalcoholic fatty liver disease and 15 body mass index (BMI)- and age-matched
      controls. The concentrations of trans-16:1n-7 and 2 other biomarkers of dairy fat
      intake, 15:0 and 17:0, were measured in plasma phospholipids and free fatty acids
      (FFAs). Liver fat was estimated by computed tomography-derived liver-spleen
      ratio. Intravenous-glucose-tolerance tests and oral-glucose-tolerance test (OGTT)
      and hyperinsulinemic-euglycemic clamps were performed to assess beta-cell
      function and hepatic and systemic insulin sensitivity. RESULTS: In multivariate
      analyses adjusted for age, sex, and BMI, phospholipid 17:0, phospholipid trans
      16:1n-7, FFA 15:0, and FFA 17:0 were inversely associated with fasting plasma
      glucose, the area under the curve for glucose during an OGTT, and liver fat.
      Phospholipid trans-16:1n-7 was also positively associated with hepatic and
      systemic insulin sensitivity. None of the biomarkers were associated with beta
      cell function. The associations between dairy fat intake and glucose tolerance
      were attenuated by adjusting for insulin sensitivity or liver fat, but
      strengthened by adjusting for beta-cell function. CONCLUSION: Although we cannot
      rule out reverse causation, these data support the hypothesis that dairy fat
      improves glucose tolerance, possibly through a mechanism involving improved
      hepatic and systemic insulin sensitivity and reduced liver fat.

PMID- 24740209
TI  - Helminth infections and micronutrients in school-age children: a systematic
      review and meta-analysis.
AB  - BACKGROUND: Helminth infections and micronutrient deficiencies are highly
      prevalent in developing countries. Neither condition typically causes overt
      disease, but they do lead to indirect morbidity such as impaired physical and
      cognitive development. OBJECTIVE: We aimed to systematically review current
      evidence on the relation of helminth infections with micronutrient status in
      school-age children worldwide. DESIGN: We included both observational studies and
      randomized controlled trials (RCTs). We applied a random-effects meta-analysis to
      estimate 1) cross-sectional associations between helminths and micronutrient
      status, 2) effects of anthelminthic treatment on micronutrient status, and 3)
      effects of micronutrient supplementation on helminth infection and reinfection.
      RESULTS: Meta-analyses of observational studies showed an association between
      helminth infections and serum retinol [standardized mean difference (SMD): -0.30;
      95% CI: -0.48, -0.13] but not serum ferritin (SMD: 0.00; 95% CI: -0.7, 0.7).
      Conversely, meta-analyses of anthelminthic treatment RCTs showed a positive
      effect on ferritin (SMD: 0.16; 95% CI: 0.09, 0.22) but not retinol (SMD: 0.04;
      95% CI: -0.06, 0.14). The number of studies on micronutrients other than ferritin
      and retinol was not sufficient for pooling. Meta-analyses of micronutrient
      supplementation RCTs showed only a modest protective effect for
      multimicronutrient interventions on helminth infection and reinfection rates (OR:
      0.77; 95% CI: 0.61, 0.97). CONCLUSIONS: In this review, we show evidence of
      distinct associations between helminth infections and micronutrients in school
      age children. More studies are needed on micronutrients other than iron and
      vitamin A and on possible helminth species-specific effects. A thorough
      comprehension of the interplay between helminth infections and micronutrients
      will help guide integrated and sustainable intervention strategies in affected
      children worldwide.

PMID- 24740210
TI  - Free-standing carbon nanotube/graphene hybrid papers as next generation
      adsorbents.
AB  - The adsorption of a series of aromatic compounds from aqueous solution onto
      purified, free-standing single-walled carbon nanotube/graphene nanoplatelet
      hybrid papers is studied both experimentally and theoretically. Experimental data
      is obtained via changes in optical absorption spectra of the aqueous solutions
      and is used to extract all parameters required to implement a semi-empirical mass
      transfer model. Agreement between experiment and theory is excellent and data
      from all compounds can be cast on a universal adsorption curve. Results indicate
      that the rate of adsorption and long-time capacity of many aromatic compounds on
      hybrid paper adsorbent significantly exceeds that of activated carbon by at least
      an order of magnitude. The combination of carbon nanotubes and graphene also
      promotes on the order of a 25% improvement in adsorption rates and capacities
      than either component alone. Hybrid nanocomposites show significant promise as
      adsorption materials used for environmental remediation efforts. 

PMID- 24740211
TI  - Alteration of the systemic and microcirculation by a single oral dose of flavan-3
      ols.
AB  - Several systematic reviews have reported that flow mediated dilatation (FMD) was
      significantly increased in subjects after ingestion of chocolate that contains
      flavan-3-ols; however, the mechanisms responsible for this effect are not clear.
      In this study, we evaluated the effects of a single oral dose of flavan-3-ols on
      the systemic circulation and microcirculation in the cremaster muscle using
      intravital video microscopy in vivo. The cremaster muscle in rats was spread over
      a plastic chamber and a gastric tube was placed into the stomach. Blood flow in
      the cremasteric artery was determined using a laser Doppler flowmeter, while
      blood pressure and heart rate were measured by the tail-cuff method. Red blood
      cell velocity in arterioles and blood flow in the artery were significantly
      increased 5 min after the administration of 10 mg/kg flavan-3-ols compared with
      distilled water treatment. The number of capillaries recruited in the cremaster
      muscle was also significantly increased 15 min after treatment. Microscopic
      observation confirmed that increased shear stress on endothelial cells was
      maintained during the measurement period. The mean arterial blood pressure and
      heart rate were also significantly elevated soon after administration and
      returned to baseline before the end of the observation period. Plasma nitrate and
      nitrite levels, and NO phosphorylation of aortic tissue were significantly
      increased at 60 min after administration of flavan-3-ols. According to these
      results, a single oral dose of flavan-3-ols elevates blood pressure and flow
      transiently, and these effects induce NO production through increased shear
      stress on endothelial cells. 

PMID- 24740213
TI  - A unified intermediate and mechanism for soot combustion on potassium-supported
      oxides.
AB  - The soot combustion mechanism over potassium-supported oxides (MgO, CeO2 and
      ZrO2) was studied to clarify the active sites and discover unified reaction
      intermediates in this typical gas-solid-solid catalytic reaction. The
      catalytically active sites were identified as free K(+) rather than K2CO3, which
      can activate gaseous oxygen. The active oxygen spills over to soot and forms a
      common intermediate, ketene, before it was further oxidized into the end product
      CO2. The existence of ketene species was confirmed by density functional theory
      (DFT) calculations. The oxygen spillover mechanism is proposed, which is
      explained as an electron transfer from soot to gaseous oxygen through the active
      K(+) sites. The latter mechanism is confirmed for the first time since it was put
      forward in 1950, not only by ultraviolet photoelectron spectroscopy (UPS) results
      but also by semi-empirical theoretical calculations. 

PMID- 24740212
TI  - Two-dimensional echocardiography using second harmonic imaging for the diagnosis
      of intracardiac right-to-left shunt: a meta-analysis of prospective studies.
AB  - Right-to-left shunting (RLS), usually through a patent foramen ovale (PFO), has
      been associated with migraine, cryptogenic stroke and hypoxemia. With emerging
      observational studies and clinical trials on the subject of PFO, there is a need
      for accurate diagnosis of PFO in patients being considered for transcatheter
      closure. While transesophageal echo (TEE) bubble study is the current standard
      reference for diagnosing PFO, transthoracic echo with second harmonic imaging
      (TTE-HI) may be a preferable screening test for RLS due to its high accuracy and
      non-invasiveness. The aim of this meta-analysis was to determine the accuracy of
      TTE-HI compared to TEE as the reference. A systematic review of Medline, Cochrane
      and Embase was done for all the prospective studies assessing for intracardiac
      RLS using TTE-HI compared to TEE as the reference; both TTE-HI and TEE were
      performed with a contrast agent and a maneuver to provoke RLS in all studies. A
      total of 15 studies with 1995 patients fulfilled the inclusion criteria. The
      weighted mean sensitivity and specificity for TTE-HI were 91 and 93 %
      respectively. Likewise, the positive and negative likelihood ratios were 13.52
      and 0.13 respectively. TTE-HI is a reliable, non-invasive test with proficient
      diagnostic accuracies. The high sensitivity and specificity of TTE-HI make it a
      useful initial screening test for RLS. If the precise anatomy is required, then
      TEE can be obtained before scheduling a patient for transcatheter PFO closure.

PMID- 24740214
TI  - Atrophic skin patches with abnormal elastic fibers as a presenting sign of the
      MASS phenotype associated with mutation in the fibrillin 1 gene.
AB  - IMPORTANCE: Marfan syndrome (MFS) is a dominantly inherited disorder of
      connective tissue caused by mutations in the fibrillin 1 gene (FBN1). The most
      common skin finding in MFS is striae distensae. Particular individuals referred
      for suspected MFS who do not completely fulfill the MFS diagnostic criteria are
      classified as having a MASS phenotype. The acronym represents the following
      manifestations: a prolapsed mitral valve, myopia, aortic root enlargement, and
      skeletal and skin manifestations. Mutations in FBN1 have been shown to be
      associated in some cases with the MASS phenotype. Skin manifestations may be an
      important clue to the diagnosis of these disorders. OBSERVATIONS: We studied a
      patient referred for unusual atrophic skin patches on the buttocks. Results of
      histopathological examination and electron microscopy demonstrated markedly
      abnormal elastic fibers. Subsequent medical genetics evaluation led ultimately to
      the diagnosis of the MASS phenotype and the discovery of an underlying FBN1
      mutation. CONCLUSIONS AND RELEVANCE: Although the clinical suspicion and
      diagnosis of MFS and related disorders are usually established by its main
      associated clinical features, including ophthalmologic, skeletal, and vascular
      involvement, clinicians should be aware of the associated skin manifestations,
      including unusual atrophic patches with abnormal elastic fibers that can
      sometimes be the first noted sign of the genetic disorder.

PMID- 24740215
TI  - [Is certified quality really better than quality? On the use of hospital and
      practice certifications].

PMID- 24740216
TI  - Twenty years of qPCR: a mature technology?
AB  - Quantitative PCR is the "gold standard" technology to quantify nucleic acids and,
      since the first report describing real-time PCR detection in 1993, its use has
      been grown exponentially. More recent technological advancements have extended
      the field of applications ranging from high-resolution melting detection to
      digital PCR. Nowadays, it is a very accessible technique, but some pitfalls
      should be overcome in order to achieve robust and reliable analysis. 

PMID- 24740217
TI  - Minimum information necessary for quantitative real-time PCR experiments.
AB  - The MIQE (minimum information for the publication of quantitative real-time PCR)
      guidelines were published in 2009 with the twin aims of providing a blueprint for
      good real-time quantitative polymerase chain reaction (qPCR) assay design and
      encouraging the comprehensive reporting of qPCR protocols. It had become
      increasingly clear that variable pre-assay conditions, poor assay design, and
      incorrect data analysis were leading to the routine publication of data that were
      often inconsistent, inaccurate, and wrong. The problem was exacerbated by a lack
      of transparency of reporting, with the details of technical information
      inadequate for the purpose of assessing the validity of published qPCR data. This
      had, and continues to have serious implications for basic research, reducing the
      potential for translating findings into valuable applications and potentially
      devastating consequences for clinical practice. Today, the rationale underlying
      the MIQE guidelines has become widely accepted, with more than 2,200 citations by
      March 2014 and editorials in Nature and related publications acknowledging the
      enormity of the problem. However, the problem we now face is rather serious:
      thousands of publications that report suspect data are populating and corrupting
      the peer-reviewed scientific literature. It will be some time before the many
      contradictions apparent in every area of the life sciences are corrected. 

PMID- 24740218
TI  - Selection of reliable reference genes for RT-qPCR analysis.
AB  - Reference genes have become the method of choice for normalization of qPCR data.
      It has been demonstrated in many studies that reference gene validation is
      essential to ensure accurate and reliable results. This chapter describes how a
      pilot study can be set up to identify the best set of reference genes to be used
      for normalization of qPCR data. The data from such a pilot study should be
      analyzed with dedicated algorithms such as geNorm to rank genes according to
      their stability--a measure for how well they are suited for normalization. geNorm
      also provides insights into the optimal number of reference genes and the overall
      quality of the selected set of reference genes. Importantly, these results are
      always in function of the sample type being studied. Guidelines are provided on
      the interpretation of the results from geNorm pilot studies as well as for the
      continued monitoring of reference gene quality in subsequent studies. For
      screening studies including a large, unbiased set of genes (e.g., complete
      miRNome) an alternative normalization method can be used: global mean
      normalization. This chapter also describes how the data from such studies can be
      used to identify reference genes for subsequent validation studies on smaller
      sets of selected genes.

PMID- 24740219
TI  - Introduction to digital PCR.
AB  - Digital PCR (dPCR) is a molecular biology technique going through a renaissance.
      With the arrival of new instrumentation dPCR can now be performed as a routine
      molecular biology assay. This exciting new technique provides quantitative and
      detection capabilities that by far surpass other methods currently used. This
      chapter is an overview of some of the applications currently being performed
      using dPCR as well as the fundamental concepts and techniques this technology is
      based on. 

PMID- 24740220
TI  - mRNA and microRNA purity and integrity: the key to success in expression
      profiling.
AB  - RNA quality control is a crucial step in guaranteeing integer nondegraded RNA and
      receiving meaningful results in gene expression profiling experiments, using
      micro-array, RT-qPCR (Reverse-Transcription quantitative PCR), or Next-Generation
      Sequencing by RNA-Seq or small-RNA Seq. Therefore, assessment of RNA integrity
      and purity is very essential prior to gene expression analysis of sample RNA to
      ensure the accuracy of any downstream applications. RNA samples should be
      nondegraded or fragmented and free of protein, genomic DNA, nucleases, and
      enzymatic inhibitors. Herein we describe the current state-of-the-art RNA quality
      assessment by combining UV/Vis spectrophotometry and microfluidic capillary
      electrophoresis. 

PMID- 24740221
TI  - Mediator probe PCR: detection of real-time PCR by label-free probes and a
      universal fluorogenic reporter.
AB  - Mediator probe PCR (MP PCR) is a novel detection format for real-time nucleic
      acid analysis. Label-free mediator probes (MP) and fluorogenic universal reporter
      (UR) oligonucleotides are combined to accomplish signal generation. Compared to
      conventional hydrolysis probe PCRs costs can thus be saved by using the same
      fluorogenic UR for signal generation in different assays. This tutorial provides
      a practical guideline to MP and UR design. MP design rules are very similar to
      those of hydrolysis probes. The major difference is in the replacement of the
      fluorophore and quencher by one UR-specific sequence tag, the mediator. Further
      protocols for the setup of reactions, to detect either DNA or RNA targets with
      clinical diagnostic target detection as models, are explained. Ready to use
      designs for URs are suggested and guidelines for their de novo design are
      provided as well, including a protocol for UR signal generation characterization.

PMID- 24740222
TI  - Absolute quantification of viral DNA: the quest for perfection.
AB  - In spite of the impressive technical refinement of the PCR technology, new
      generation real-time PCR assays still suffer from two major limitations: the
      impossibility to control both for PCR artifacts (with the important caveat of
      false-negative results) and for the efficiency of nucleic acid recovery during
      the preliminary extraction phase of DNA from the biological sample. The
      calibrator technology developed at the Unit of Human Virology overcomes both of
      these limitations, leading to a substantially higher degree of accuracy and
      reproducibility in the quantification, which is especially useful for the
      measurement of pathogen loads in sequential samples and for the reliable
      detection of low-copy pathogens.

PMID- 24740223
TI  - A multiplex real-time PCR-platform integrated into automated extraction method
      for the rapid detection and measurement of oncogenic HPV type-specific viral DNA
      load from cervical samples.
AB  - The persistent infection with most frequent high-risk (HR)-HPV types (HPV-16, 
      18, -31, -33, -45, -52, and -58) is considered to be the true precursor of
      neoplastic progression. HR-HPV detection and genotyping is the most effective and
      accurate approach in screening of the early cervical lesions and cervical cancer,
      although also the HR-HPV DNA load is considered an ancillary marker for
      persistent HPV infection. Here, it is described an in-house multiplex
      quantitative real-time PCR (qPCR)-based typing system for the rapid detection and
      quantitation of the most common HR-HPV genotypes from cervical cytology screening
      tests. First, a separate qPCR assay to quantify a single-copy gene is recommended
      prior to screening (prescreening assay) to verify the adequate cellularity of the
      sample and the quality of DNA extracted and to normalize the HPV copy number per
      genomic DNA equivalent in the sample. Subsequently, to minimize the number of
      reactions, two multiplex qPCR assays (first line screening) are performed to
      detect and quantify HPV-16, -18, -31, -33, -45, -52, and -58 (HPV-18 and -45 are
      measured together by single-fluorophore). In addition, a multiplex qPCR assay
      specific for HPV-18 and HPV-45 is also available to type precisely the samples
      found to be positive for one of the two strains. Finally, two nucleic acid
      extraction methods are proposed by using a 96-well plate format: one manual
      method (supported by centrifuge or by vacuum) and one automated method integrated
      into a robotic liquid handler workstation to minimize material and hands-on time.
      In conclusion, this system provides a reliable high-throughput method for the
      rapid detection and quantitation of HR-HPV DNA load in cervical samples.

PMID- 24740224
TI  - Real-time PCR detection of Mycoplasma pneumoniae in the diagnosis of community
      acquired pneumonia.
AB  - Polymerase chain reaction is a useful technique in microbial diagnostics to
      detect and quantify DNA or RNA of low abundance. Bacterial and viral nucleic acid
      can be amplified by PCR upon clinical sample extraction using specific primers
      for classical qualitative PCR and primers and probes for real-time PCR. Here we
      describe the Scorpion-probe real-time PCR-based assay that offers thermodynamic
      advantages due to its kinetic reaction and provides faster performances compared
      to a classical double-labeled probe-based assays.

PMID- 24740225
TI  - A sensible technique to detect mollicutes impurities in human cells cultured in
      GMP condition.
AB  - In therapeutic trials the use of manipulated cell cultures for clinical
      applications is often required. Mollicutes microorganism contamination of tissue
      cultures is a major problem because it can determine various and severe
      alterations in cellular function. Thus methods able to detect and trace cell
      cultures with Mollicutes contamination are needed in the monitoring of cells
      grown under good manufacturing practice conditions, and cell lines in continuous
      culture must be tested at regular intervals. We here describe a multiplex
      quantitative polymerase chain reaction assay able to detect contaminant
      Mollicutes species in a single-tube reaction through analysis of 16S-23S rRNA
      intergenic spacer regions and Tuf and P1 cytoadhesin genes. The method shows a
      sensitivity, specificity, and robustness comparable with the culture and the
      indicator cell culture as required by the European Pharmacopoeia guidelines and
      was validated following International Conference on Harmonization guidelines and
      Food and Drug Administration requirements.

PMID- 24740226
TI  - Real-time quantification assay to monitor BCR-ABL1 transcripts in chronic myeloid
      leukemia.
AB  - The BCR-ABL1 fusion gene, the causative lesion of chronic myeloid leukemia (CML)
      in >95 % of newly presenting patients, offers both a therapeutic and diagnostic
      target. Reverse-transcription quantitative polymerase chain reaction technology
      (RT-qPCR), utilizing primer-probe combinations directed to exons flanking the
      breakpoint junctional region, offers very high levels of both specificity and
      sensitivity, in a scalable, robust, and cost-effective assay. 

PMID- 24740227
TI  - A reliable assay for rapidly defining transplacental metastasis using
      quantitative PCR.
AB  - To choose the most appropriate treatment for children affected by a
      transplacental metastasis, it is crucial to ascertain the maternal origin of the
      tumor. Up-to-date conclusive diagnosis is generally achieved through fluorescence
      in situ hybridization or karyotyping analysis. Herein, we report an alternative,
      reliable assay for rapidly defining vertical cancer transmission to the fetus by
      using quantitative polymerase chain reaction. Our assay indicates that
      quantification of the copy number of the sex chromosomes by specific short tandem
      repeats markers, in genomic DNA purified from the tumor biopsy cells, could be
      used to correctly evaluate transplacental metastasis events.

PMID- 24740228
TI  - Circulating cell-free DNA in cancer.
AB  - This papers deals with the preanalytical and analytical phase of cell-free DNA
      analysis, highlighting some criticism on sample collection and extraction. We
      describe a method to accurately quantify total cfDNA in plasma and our particular
      approach to the measurement of tumor deriving cfDNA. 

PMID- 24740229
TI  - Gene expression analysis by qPCR in clinical kidney transplantation.
AB  - Patients with a kidney transplant may encounter chronic dysfunction of their
      graft. Once damage in the graft has established, therapeutic intervention is less
      efficient. Clinical parameters and morphologic evaluation of biopsies are used
      for determining diagnosis and prognosis of the patient. Quantitative polymerase
      chain reaction (qPCR) may be integrated in clinical practice to facilitate
      routine diagnostics, risk assessment with respect to graft outcome, and
      determination of the response to therapy by the patient. The success of qPCR
      assays is highly dependent on the adequacy of the methodological procedures
      performed. Here, we describe tips and tricks for processing patient material, RNA
      analysis, and qPCR primer design and gene expression analyses. 

PMID- 24740230
TI  - Posttranscriptional regulatory networks: from expression profiling to integrative
      analysis of mRNA and microRNA data.
AB  - Protein coding RNAs are posttranscriptionally regulated by microRNAs, a class of
      small noncoding RNAs. Insights in messenger RNA (mRNA) and microRNA (miRNA)
      regulatory interactions facilitate the understanding of fine-tuning of gene
      expression and might allow better estimation of protein synthesis. However, in
      silico predictions of mRNA-microRNA interactions do not take into account the
      specific transcriptomic status of the biological system and are biased by false
      positives. One possible solution to predict rather reliable mRNA-miRNA relations
      in the specific biological context is to integrate real mRNA and miRNA
      transcriptomic data as well as in silico target predictions. This chapter
      addresses the workflow and methods one can apply for expression profiling and the
      integrative analysis of mRNA and miRNA data, as well as how to analyze and
      interpret results, and how to build up models of posttranscriptional regulatory
      networks. 

PMID- 24740231
TI  - Clinical applications using digital PCR.
AB  - Molecular diagnostics and disease-specific tailored treatments are now being
      introduced to patients at many hospitals and clinics throughout the world (Strain
      and Richman, Curr Opin HIV AIDS 8:106-110, 2013) and becoming prevalent in the
      nonscientific literature. Instead of generically using a "one treatment fits all"
      approach that may have varying levels of effectiveness to different patients,
      patient-specific molecular profiling based on the genetic makeup of the disease
      and/or a more accurate pathogen titer could provide more effective treatments
      with fewer unwanted side effects. One commonly known example of this scenario is
      epidermal growth factor receptor (EGFR). EGFR is upregulated in many cancers,
      including many lung and colorectal cancers. Commonly used treatments for these
      include the receptor blockers cetuximab or panitumumab and tyrosine kinase
      inhibitors erlotinib or gefitinib. These agents are effective at reducing out-of
      control cell cycling and tumor proliferation, but only if downstream signaling
      kinases and phosphatases are not mutated. Known oncogenes such as BRAF V600E and
      KRAS G12/13 that are constitutively activated render these treatments
      ineffective. The use of known ineffective drugs and treatments can thus be
      avoided reducing time to more effective treatments, reducing cost, and increasing
      patient well-being. Although digital PCR is for all practical purposes a "new"
      technology, there is already tremendous interest in its potential for the
      clinical diagnostics arena. Specificity of the information acquired, accuracy of
      results, time to results, and cost per sample analyzed are making dPCR an
      attractive tool for this field. Three areas where dPCR will have a noticeable
      impact are pathogen/viral detection and quantitation, copy number variations, and
      rare mutation detection and abundance, but it will inevitably expand from these
      as the technology becomes more and more prevalent. This chapter discusses digital
      PCR assay optimization and validation, pathogen/viral detection and quantitation,
      copy number variation, and rare mutation abundance assays. The sample methods
      described below utilize the QX100/QX200 methodologies, but with the exception of
      reaction sub-partitioning (dependent on the instrumentation used) most other
      parameters remain the same.

PMID- 24740232
TI  - Developing noninvasive diagnosis for single-gene disorders: the role of digital
      PCR.
AB  - Cell-free fetal DNA constitutes approximately 10 % of the cell-free DNA found in
      maternal plasma and can be used as a reliable source of fetal genetic material
      for noninvasive prenatal diagnosis (NIPD) from early pregnancy. The relatively
      high levels of maternal background can make detection of paternally inherited
      point mutations challenging. Diagnosis of inheritance of autosomal recessive
      disorders using qPCR is even more challenging due to the high background of
      mutant maternal allele. Digital PCR is a very sensitive modified method of
      quantitative real-time PCR (qPCR), allowing absolute quantitation and rare allele
      detection without the need for standards or normalization. Samples are diluted
      and then partitioned into a large number of small qPCR reactions, some of which
      contain the target molecule and some which do not; the proportion of positive
      reactions can be used to calculate the concentration of targets in the initial
      sample. Here we discuss the use of digital PCR as an accurate approach to NIPD
      for single-gene disorders. 

PMID- 24740234
TI  - Neuropsychological factors and bariatric surgery: a review.
AB  - Obesity has become a global epidemic with associated physical, psychological, and
      cognitive deficits that tax the healthcare system and result in a significant
      economic burden. These costs have necessitated treatment measures to reduce the
      incidence of obesity as well as comorbidities associated with obesity. We review
      the current literature in order to describe the pre-surgical psychological and
      cognitive characteristics of individuals undergoing bariatric surgery and the
      possible changes in these functions following surgery. We discuss the importance
      of a pre-surgical evaluation that adequately evaluates cognitive and emotional
      functioning and what this evaluation should entail. Finally, we discuss recent
      trends in the types of bariatric surgeries being performed and how these changes
      may influence subsequent physical, cognitive, and emotional health. 

PMID- 24740233
TI  - Protein kinase D interacts with neuronal nitric oxide synthase and phosphorylates
      the activatory residue serine 1412.
AB  - Neuronal Nitric Oxide Synthase (nNOS) is the biosynthetic enzyme responsible for
      nitric oxide (.NO) production in muscles and in the nervous system. This
      constitutive enzyme, unlike its endothelial and inducible counterparts, presents
      an N-terminal PDZ domain known to display a preference for PDZ-binding motifs
      bearing acidic residues at -2 position. In a previous work, we discovered that
      the C-terminal end of two members of protein kinase D family (PKD1 and PKD2)
      constitutes a PDZ-ligand. PKD1 has been shown to regulate multiple cellular
      processes and, when activated, becomes autophosphorylated at Ser 916, a residue
      located at -2 position of its PDZ-binding motif. Since nNOS and PKD are spatially
      enriched in postsynaptic densities and dendrites, the main objective of our study
      was to determine whether PKD1 activation could result in a direct interaction
      with nNOS through their respective PDZ-ligand and PDZ domain, and to analyze the
      functional consequences of this interaction. Herein we demonstrate that PKD1
      associates with nNOS in neurons and in transfected cells, and that kinase
      activation enhances PKD1-nNOS co-immunoprecipitation and subcellular
      colocalization. However, transfection of mammalian cells with PKD1 mutants and
      yeast two hybrid assays showed that the association of these two enzymes does not
      depend on PKD1 PDZ-ligand but its pleckstrin homology domain. Furthermore, this
      domain was able to pull-down nNOS from brain extracts and bind to purified nNOS,
      indicating that it mediates a direct PKD1-nNOS interaction. In addition, using
      mass spectrometry we demonstrate that PKD1 specifically phosphorylates nNOS in
      the activatory residue Ser 1412, and that this phosphorylation increases nNOS
      activity and .NO production in living cells. In conclusion, these novel findings
      reveal a crucial role of PKD1 in the regulation of nNOS activation and synthesis
      of .NO, a mediator involved in physiological neuronal signaling or neurotoxicity
      under pathological conditions such as ischemic stroke or neurodegeneration.

PMID- 24740235
TI  - Current concepts in psychodermatology.
AB  - Several diagnoses in the new DSM-5 chapter on 'Obsessive-Compulsive and Related
      Disorders' directly relate to psychodermatology. The new excoriation (skin
      picking) disorder (SPD) and trichotillomania (TTM) both manifest as recurrent
      body-focused repetitive behaviors that have compulsive and dissociative features,
      the latter being more prevalent in TTM than SPD. The DSM-5 refers to SPD and TTM
      occurring without full awareness or preceding tension, however does not
      specifically mention the possible role of dissociation. This has important
      treatment implications, as patients with high dissociative symptoms are not
      likely to respond to the standard treatments for obsessive-compulsive disorder.
      Body dysmorphic disorder (BDD), which is frequently associated with cutaneous
      body image (CBI) dissatisfaction, is present in 9%-15% of dermatology patients.
      Treatment guidelines in dermatology are increasingly considering the psychosocial
      morbidity related to CBI in their treatment outcome measures. The presence of
      BDD, if unrecognized, may therefore directly affect the dermatologic treatment
      regimens offered to the patient.

PMID- 24740237
TI  - From text tagging to decision support.

PMID- 24740236
TI  - The potential of accelerating early detection of autism through content analysis
      of YouTube videos.
AB  - Autism is on the rise, with 1 in 88 children receiving a diagnosis in the United
      States, yet the process for diagnosis remains cumbersome and time consuming.
      Research has shown that home videos of children can help increase the accuracy of
      diagnosis. However the use of videos in the diagnostic process is uncommon. In
      the present study, we assessed the feasibility of applying a gold-standard
      diagnostic instrument to brief and unstructured home videos and tested whether
      video analysis can enable more rapid detection of the core features of autism
      outside of clinical environments. We collected 100 public videos from YouTube of
      children ages 1-15 with either a self-reported diagnosis of an ASD (N = 45) or
      not (N = 55). Four non-clinical raters independently scored all videos using one
      of the most widely adopted tools for behavioral diagnosis of autism, the Autism
      Diagnostic Observation Schedule-Generic (ADOS). The classification accuracy was
      96.8%, with 94.1% sensitivity and 100% specificity, the inter-rater correlation
      for the behavioral domains on the ADOS was 0.88, and the diagnoses matched a
      trained clinician in all but 3 of 22 randomly selected video cases. Despite the
      diversity of videos and non-clinical raters, our results indicate that it is
      possible to achieve high classification accuracy, sensitivity, and specificity as
      well as clinically acceptable inter-rater reliability with nonclinical personnel.
      Our results also demonstrate the potential for video-based detection of autism in
      short, unstructured home videos and further suggests that at least a percentage
      of the effort associated with detection and monitoring of autism may be mobilized
      and moved outside of traditional clinical environments. 

PMID- 24740239
TI  - 'Between the flags': implementing a rapid response system at scale.
AB  - While many hospitals are implementing rapid response systems (RRSs) to attend to
      deteriorating patients in a systematic way, there is little documented evidence
      on system-wide approaches to adopting RRSs. Here, we report on an initiative
      which enrolled 220 hospitals in New South Wales, Australia. The 'between the
      flags' approach was modelled on Australia's surf lifesaving experience, where
      qualified lifesavers perform thousands of rescues each year. Patients in
      hospitals who are identified as being 'between the flags' are given special
      attention, just like beach goers. 

PMID- 24740238
TI  - A marginal benefit approach for vaccinating influenza "superspreaders".
AB  - BACKGROUND: There is widespread recognition that interventions targeting
      "superspreaders" are more effective at containing epidemics than strategies aimed
      at the broader POPULATION: However, little attention has been devoted to
      determining optimal levels of coverage for targeted vaccination strategies, given
      the nonlinear relationship between program scale and the costs and benefits of
      identifying and successfully administering vaccination to potential
      superspreaders. METHODS: We developed a framework for such an assessment derived
      from a transmission model of seasonal influenza parameterized to emulate typical
      seasonal influenza epidemics in the US. We used this framework to estimate how
      the marginal benefit of expanded targeted vaccination changes with the proportion
      of the target population already vaccinated. RESULTS: The benefit of targeting
      additional superspreaders varies considerably as a function of both the baseline
      vaccination coverage and proximity to the herd immunity threshold. The general
      form of the marginal benefit function starts low, particularly for severe
      epidemics, increases monotonically until its peak at the point of herd immunity,
      and then plummets rapidly. We present a simplified transmission model, primarily
      designed to convey qualitative insight rather than quantitative precision. With
      appropriate contact data, future work could address more complex population
      structures, such as age structure and assortative mixing patterns. Our
      illustrative example highlights the general economic and epidemiological findings
      of our method but does not address intervention design, policy, and resource
      allocation issues related to practical implementation of this particular
      scenario. CONCLUSIONS: Our approach offers a means of estimating willingness to
      pay for search costs associated with targeted vaccination of superspreaders,
      which can inform policies regarding whether a targeted intervention should be
      implemented and, if so, up to what levels.

PMID- 24740240
TI  - Quality of life amongst older Brazilians: a cross-cultural validation of the CASP
      19 into Brazilian-Portuguese.
AB  - INTRODUCTION: As population ageing becomes a global phenomenon the need to
      understand the quality of life of older people around the world has become
      increasingly salient. The CASP-19 is a well established measure of quality of
      later life. The scale is composed of 19 items which map onto the four domains of
      control (C), Autonomy (A), Self-Realisation (S) and Pleasure (P). It has already
      been translated to 12 languages and has been used in a number of national and
      international studies. However use of the scale outside of Europe has been very
      limited. The objective of this study was to translate and evaluate the use of the
      CASP-19 amongst older Brazilians. METHODS: The CASP-19 was translated from
      English to Portuguese, back-translated and submitted to an analysis of
      equivalence by a committee of judges. The scale was then administered to a sample
      of community dwelling older people in Recife, Brazil (n = 87), and tested for
      psychometric properties. The Control and Pleasure domains exhibited good internal
      consistency. By removing one item from each of the Autonomy and Self Realisation
      domains their internal consistency was improved. RESULTS: The mean age of the
      sample was 75.6+/-0.7 years, subjects were mainly female (52.9%), white (52.9%),
      who lived without a partner (54%), and had a monthly income varying from USD
      340.00 to USD 850.00. Translation and cross-cultural adaptation permitted good
      understanding and applicability of final version. Psychometric analyses revealed
      that the removal of two items improved the internal consistency of the Autonomy
      and Pleasure domains. Confirmatory factor analyses suggest that a 16 item, four
      factor, model best fits the data. CONCLUSION: In this small exploratory study the
      CASP-19 Brazil demonstrated good psychometric properties. It was easy to use for
      both participants and researchers. Hopefully future studies in Brazil will employ
      the scale so that more direct cross national comparisons can be made with older
      people in Europe and the US.

PMID- 24740241
TI  - Control of intermale aggression by medial prefrontal cortex activation in the
      mouse.
AB  - Aggressive behavior is widely observed throughout the animal kingdom because of
      its adaptiveness for social animals. However, when aggressive behavior exceeds
      the species-typical level, it is no longer adaptive, so there should be a
      mechanism to control excessive aggression to keep it within the adaptive range.
      Using optogenetics, we demonstrate that activation of excitatory neurons in the
      medial prefrontal cortex (mPFC), but not the orbitofrontal cortex (OFC), inhibits
      inter-male aggression in mice. At the same time, optogenetic silencing of mPFC
      neurons causes an escalation of aggressive behavior both quantitatively and
      qualitatively. Activation of the mPFC suppresses aggressive bursts and reduces
      the intensity of aggressive behavior, but does not change the duration of the
      aggressive bursts. Our findings suggest that mPFC activity has an inhibitory role
      in the initiation and execution, but not the termination, of aggressive behavior,
      and maintains such behavior within the adaptive range. 

PMID- 24740242
TI  - Validity of hydration non-invasive indices during the weightcutting and official
      weigh-in for Olympic combat sports.
AB  - BACKGROUND: In Olympic combat sports, weight cutting is a common practice aimed
      to take advantage of competing in weight divisions below the athlete's normal
      weight. Fluid and food restriction in combination with dehydration (sauna and/or
      exercise induced profuse sweating) are common weight cut methods. However, the
      resultant hypohydration could adversely affect health and performance outcomes.
      PURPOSE: The aim of this study is to determine which of the routinely used non
      invasive measures of dehydration best track urine osmolality, the gold standard
      non-invasive test. METHOD: Immediately prior to the official weigh-in of three
      National Championships, the hydration status of 345 athletes of Olympic combat
      sports (i.e., taekwondo, boxing and wrestling) was determined using five separate
      techniques: i) urine osmolality (UOSM), ii) urine specific gravity (USG), iii)
      urine color (UCOL), iv) bioelectrical impedance analysis (BIA), and v) thirst
      perception scale (TPS). All techniques were correlated with UOSM divided into
      three groups: euhydrated (G1; UOSM 250-700 mOsm . kg H2O(-1)), dehydrated (G2;
      UOSM 701-1080 mOsm . kg H2O(-1)), and severely dehydrated (G3; UOSM 1081-1500
      mOsm . kg H2O(-1)). RESULTS: We found a positive high correlation between the
      UOSM and USG (r = 0.89: p = 0.000), although this relationship lost strength as
      dehydration increased (G1 r = 0.92; G2 r = 0.73; and G3 r = 0.65; p = 0.000).
      UCOL showed a moderate although significant correlation when considering the
      whole sample (r = 0.743: p = 0.000) and G1 (r = 0.702: p = 0.000) but low
      correlation for the two dehydrated groups (r = 0.498-0.398). TPS and BIA showed
      very low correlation sizes for all groups assessed. CONCLUSION: In a wide range
      of pre-competitive hydration status (UOSM 250-1500 mOsm . kg H2O(-1)), USG is
      highly associated with UOSM while being a more affordable and easy to use
      technique. UCOL is a suitable tool when USG is not available. However, BIA or TPS
      are not sensitive enough to detect hypohydration at official weight-in before an
      Olympic combat championship.

PMID- 24740243
TI  - Cationic nanoemulsions bearing ciprofloxacin surf-plexes enhances its therapeutic
      efficacy in conditions of E. coli induced peritonitis and sepsis.
AB  - PURPOSE: Chitosan (CH) coated ciprofloxacin-sodium deoxycholate surfplex (CFn
      SDC) loaded nanoemulsion (LE-CH-CFn-SDC) developed in order to improve tissue
      penetration of the CFn as well as to mop up the endotoxin (Lipopolysaccharides or
      LPS) released from bacteria during antibiotic treatment. METHODS: Size and zeta
      potential was evaluated for nanoemulsions prepared by high-speed homogenization
      and sonication. Drug analysis in samples was done by HPLC equipped with
      fluorescence detector. All formulations were evaluated for any change in LPS
      induced NO and TNF-alpha release and ROS generation in J774 macrophages. The
      formulations were also evaluated for in-vitro killing efficiency on E-Coli. The
      efficacy of formulations in terms of survival and pharmacokinetics and inhibition
      of induction of cytokines was carried out in E-coli induced peritonitis model in
      rats. LE-CH-CFn-SDC interacted with LPS both by electrostatic and hydrophobic
      interactions. RESULTS: LE-CH-CFn-SDC resulted in reduction of endotoxin release
      and MIC values for E. coli. LE-CH-CFn-SDC also reduced NO and TNF-alpha as well
      as ROS generation by reducing the uptake of LPS in J774 macrophages. LE-CH-CFn
      SDC improved CFn pharmacokinetics and tissue distribution, by reducing the
      bacterial burden, LPS and cytokines (TNF-alpha and IL-6) thereby improving
      survival in a rat model of E. coli induced peritonitis. CONCLUSION: In
      conclusion, this work highlights the effectiveness of the chitosan-coated
      nanoemulsion as intracorporeal approach for therapeutic intervention of E. coli
      induced peritonitis as well as in sepsis.

PMID- 24740244
TI  - Insight into mechanisms of cellular uptake of lipid nanoparticles and
      intracellular release of small RNAs.
AB  - PURPOSE: Understanding mechanisms of cellular uptake and intracellular release
      would enable better design of nanocarriers for delivery of nucleic acids such as
      siRNA and microRNA (miRNA). METHOD: In this study, we investigated cellular
      pharmacokinetics of siRNA by co-encapsulating fluorescently labeled siRNA and
      molecular beacon (MB) in four different formulations of cationic lipid
      nanoparticles (LNPs). A miRNA mimic was also used as a probe for investigating
      cellular pharmacokinetics, which correlated well with RNAi activities. RESULTS:
      We tried to find the best LNP formulation based on the combination of DOTMA and
      DODMA. When the DOTMA/DODMA ratio was at 5/40, the LNP containing a luciferase
      siRNA produced the highest gene silencing activity. The superior potency of
      DOTMA/DODMA could be attributed to higher uptake and improved ability to
      facilitate siRNA release from endosomes subsequent to uptake. CONCLUSIONS: Our
      findings may provide new insights into RNAi transfection pathways and have
      implications on cationic LNP design.

PMID- 24740245
TI  - A population pharmacodynamic model for lactate dehydrogenase and neuron specific
      enolase to predict tumor progression in small cell lung cancer patients.
AB  - The development of individualized therapies poses a major challenge in oncology.
      Significant hurdles to overcome include better disease monitoring and early
      prediction of clinical outcome. Current clinical practice consists of using
      Response Evaluation Criteria in Solid Tumors (RECIST) to categorize response to
      treatment. However, the utility of RECIST is restricted due to limitations on the
      frequency of measurement and its categorical rather than continuous nature. We
      propose a population modeling framework that relates circulating biomarkers in
      plasma, easily obtained from patients, to tumor progression levels assessed by
      imaging scans (i.e., RECIST categories). We successfully applied this framework
      to data regarding lactate dehydrogenase (LDH) and neuron specific enolase (NSE)
      concentrations in patients diagnosed with small cell lung cancer (SCLC). LDH and
      NSE have been proposed as independent prognostic factors for SCLC. However, their
      prognostic and predictive value has not been demonstrated in the context of
      standard clinical practice. Our model incorporates an underlying latent variable
      ("disease level") representing (unobserved) tumor size dynamics, which is assumed
      to drive biomarker production and to be influenced by exposure to treatment;
      these assumptions are in agreement with the known physiology of SCLC and these
      biomarkers. Our model predictions of unobserved disease level are strongly
      correlated with disease progression measured by RECIST criteria. In conclusion,
      the proposed framework enables prediction of treatment outcome based on
      circulating biomarkers and therefore can be a powerful tool to help clinicians
      monitor disease in SCLC. 

PMID- 24740246
TI  - Progressively reducing regulatory burden.
AB  - Principles of dissolution science have been applied to allow waiver of in vivo
      bioequivalence studies for oral immediate release solid dosage forms, providing
      certain stipulations are met. This approach reduces regulatory burden without
      sacrificing product quality and performance requirements that assure continuing
      equivalence. These principles are broadly applicable to other dosage forms and
      routes of administration. In this article, we postulate a further opportunity,
      which relies on a determination of "optimal performance" for nonsolution orally
      administered drug products. The determination can be applied to certain highly
      soluble and rapidly dissolving drug products without further study, paving the
      way possibly for even further reductions in regulatory burden. 

PMID- 24740247
TI  - 3D ear identification based on sparse representation.
AB  - Biometrics based personal authentication is an effective way for automatically
      recognizing, with a high confidence, a person's identity. Recently, 3D ear shape
      has attracted tremendous interests in research field due to its richness of
      feature and ease of acquisition. However, the existing ICP (Iterative Closet
      Point)-based 3D ear matching methods prevalent in the literature are not quite
      efficient to cope with the one-to-many identification case. In this paper, we aim
      to fill this gap by proposing a novel effective fully automatic 3D ear
      identification system. We at first propose an accurate and efficient template
      based ear detection method. By utilizing such a method, the extracted ear regions
      are represented in a common canonical coordinate system determined by the ear
      contour template, which facilitates much the following stages of feature
      extraction and classification. For each extracted 3D ear, a feature vector is
      generated as its representation by making use of a PCA-based local feature
      descriptor. At the stage of classification, we resort to the sparse
      representation based classification approach, which actually solves an l1
      minimization problem. To the best of our knowledge, this is the first work
      introducing the sparse representation framework into the field of 3D ear
      identification. Extensive experiments conducted on a benchmark dataset
      corroborate the effectiveness and efficiency of the proposed approach. The
      associated Matlab source code and the evaluation results have been made publicly
      online available at http://sse.tongji.edu.cn/linzhang/ear/srcear/srcear.htm. 

PMID- 24740249
TI  - QTc prolongation with asenapine.

PMID- 24740248
TI  - C-MYC aberrations as prognostic factors in diffuse large B-cell lymphoma: a meta
      analysis of epidemiological studies.
AB  - OBJECTIVES: Various studies have investigated the prognostic value of C-MYC
      aberrations in diffuse large B-cell lymphoma (DLBCL). However, the role of C-MYC
      as an independent prognostic factor in clinical practice remains controversial. A
      systematic review and meta-analysis were performed to clarify the clinical
      significance of C-MYC aberrations in DLBCL patients. METHODS: The pooled hazard
      ratios (HRs) for overall survival (OS) and event-free survival (EFS) were
      calculated as the main effect size estimates. The procedure was conducted
      according to the Cochrane handbook and PRISMA guidelines, including the use of a
      heterogeneity test, publication bias assessment, and meta-regression, as well as
      subgroup analyses. RESULTS: Twenty-four eligible studies enrolling 4662 patients
      were included in this meta-analysis. According to the nature of C-MYC aberrations
      (gene, protein, and mRNA), studies were divided into several subgroups. For DLBCL
      patients with C-MYC gene abnormalities, the combined HR was 2.22 (95% confidence
      interval, 1.89 to 2.61) for OS and 2.29 (95% confidence interval, 1.81 to 2.90)
      for EFS, compared to patients without C-MYC gene abnormalities. For DLBCL
      patients with overexpression of C-MYC protein and C-MYC mRNA, pooled HRs for OS
      were 2.13 and 1.62, respectively. C-MYC aberrations appeared to play an
      independent role among other well-known prognostic factors in DLBCL. Addition of
      rituximab could not overcome the inferior prognosis conferred by C-MYC.
      CONCLUSION: The present systematic review and meta-analysis confirm the
      prognostic value of C-MYC aberrations. Screening of C-MYC should have definite
      prognostic meaning for DLBCL stratification, thus guaranteeing a more tailored
      therapy.

PMID- 24740250
TI  - Neuropsychiatric symptoms as the presenting feature of acquired hepatocerebral
      degeneration.

PMID- 24740251
TI  - Time for change: Homicide bombers, not suicide bombers.

PMID- 24740252
TI  - A case of priapism associated with paliperidone.

PMID- 24740253
TI  - The clinical characteristics of obsessive compulsive disorder associated with
      high levels of schizotypy.
AB  - OBJECTIVES: This study aims to examine the characteristics of obsessive
      compulsive disorder (OCD) associated with high levels of schizotypy. METHODS:
      Using the Schizotypal Personality Questionnaire (SPQ) with 177 individuals with
      OCD, patients with OCD and high levels of schizotypy (OCD-HS) were compared to
      patients with OCD and low levels of schizotypy (OCD-LS) on a range of clinical
      characteristics. Self-report and clinician-administered instruments were used.
      Results were adjusted for the severity of OCD symptoms, age, marital status and
      comorbidity using logistic regression. RESULTS: Patients with OCD-HS were younger
      and less likely to have been married. OCD-HS was associated with higher rates of
      symmetry/order obsessions, ordering/arranging compulsions, checking compulsions,
      co-occurring major depression, post-traumatic stress disorder, substance use
      disorders and greater general psychopathology. Previously reported associations,
      such as higher total scores on the Yale-Brown Obsessive Compulsive Scale (Y-BOCS)
      were not significant when adjusted for differences in demographic variables and
      comorbidity. CONCLUSIONS: Patients with OCD-HS were associated with specific OCD
      symptoms and comorbid conditions and may warrant a specific treatment approach.

PMID- 24740255
TI  - Helical nanostructures based on DNA self-assembly.
AB  - Recent advances in design and fabrication of helical nanostructures based on DNA
      self-assembly are reviewed. These helical nanostructures are either constructed
      entirely by DNA or based on DNA guided metal nanoparticles self-assembly.
      Biophysical properties and optical responses of corresponding helical
      nanostructures are also discussed. 

PMID- 24740254
TI  - Molecular characteristics, mRNA expression, and alternative splicing of a
      ryanodine receptor gene in the oriental fruit fly, Bactrocera dorsalis (Hendel).
AB  - Ryanodine receptors (RyRs) are a distinct class of ligand-gated channels
      controlling the release of calcium from intracellular stores. The emergence of
      diamide insecticides, which selectively target insect RyRs, has promoted the
      study of insect RyRs. In the present study, the full-length RyR cDNA (BdRyR) was
      cloned and characterized from the oriental fruit fly, Bactrocera dorsalis
      (Hendel), a serious pest of fruits and vegetables throughout East Asia and the
      Pacific Rim. The cDNA of BdRyR contains a 15,420-bp open reading frame encoding
      5,140 amino acids with a predicted molecular weight of 582.4 kDa and an
      isoelectric point of 5.38. BdRyR shows a high level of amino acid sequence
      identity (78 to 97%) to other insect RyR isoforms. All common structural features
      of the RyRs are present in the BdRyR, including a well-conserved C-terminal
      domain containing consensus calcium-binding EF-hands and six transmembrane
      domains, and a large N-terminal domain. Quantitative real-time PCR analyses
      revealed that BdRyR was expressed at the lowest and highest levels in egg and
      adult, respectively, and that the BdRyR expression levels in the third instar
      larva, pupa and adult were 166.99-, 157.56- and 808.56-fold higher, respectively,
      than that in the egg. Among different adult body parts, the highest expression
      level was observed in the thorax compared with the head and abdomen. In addition,
      four alternative splice sites were identified in the BdRyR gene, with the first,
      ASI, being located in the central part of the predicted second spore lysis A/RyR
      domain. Diagnostic PCR analyses revealed that alternative splice variants were
      generated not only in a tissue-specific manner but also in a developmentally
      regulated manner. These results lay the foundation for further understanding the
      structural and functional properties of BdRyR, and the molecular mechanisms for
      target site resistance in B. dorsalis. 

PMID- 24740256
TI  - Recalcitrant bubbles.
AB  - We demonstrate that thermocapillary forces may drive bubbles against liquid flow
      in 'anomalous' mixtures. Unlike 'ordinary' liquids, in which bubbles migrate
      towards higher temperatures, we have observed vapour bubbles migrating towards
      lower temperatures, therefore against the flow. This unusual behaviour may be
      explained by the temperature dependence of surface tension of these binary
      mixtures. Bubbles migrating towards their equilibrium position follow an
      exponential trend. They finally settle in a stationary position just 'downstream'
      of the minimum in surface tension. The exponential trend for bubbles in
      'anomalous' mixtures and the linear trend in pure liquids can be explained by a
      simple model. For larger bubbles, oscillations were observed. These oscillations
      can be reasonably explained by including an inertial term in the equation of
      motion (neglected for smaller bubbles). 

PMID- 24740258
TI  - Artisanal Green Turtle, Chelonia mydas, fishery of Caribbean Nicaragua: I. Catch
      rates and trends, 1991-2011.
AB  - This is the first assessment of catch rates for the legal, artisanal green
      turtle, Chelonia mydas, fishery in Caribbean Nicaragua. Data were collected by
      community members, monitoring up to 14 landing sites from 1991 to 2011. We
      examined take levels, and temporal and spatial variability in catch rates for the
      overall fishery, by region, and community using General Additive Mixed Models
      (GAMMs). More than 171,556 green turtles were killed during the period, with a
      mean estimated minimum 8,169+/-2,182 annually. There was a statistically
      significant decline in catch rates overall. Catch rates peaked in 1997 and 2002,
      followed by a downward trend, particularly from mid-2008 to the end of the study
      period. Similar downward trends were evident in both study regions. Community
      specific catch rate trends also indicated declines with decreases ranging from
      21% to 90%. Decrease in catch rates in Nicaragua is cause for concern even though
      the principal source rookery at Tortuguero, Costa Rica, shows an increase in
      nesting activity. Explanations for the apparent discrepancy between the
      increasing trend at Tortuguero and decreasing catch rate trends in Nicaragua
      include: i) an increase in reproductive output, ii) insufficient time has passed
      to observe the impact of the fishery on the rookery due to a time lag, iii)
      changes in other segments of the population have not been detected since only
      nesting activity is monitored, iv) the expansive northern Nicaragua foraging
      ground may provide a refuge for a sufficient portion of the Tortuguero rookery,
      and/or v) a larger than expected contribution of non-Tortuguero rookeries
      occurring in Nicaragua turtle fishing areas. Our results highlight the need for
      close monitoring of rookeries and in-water aggregations in the Caribbean. Where
      consumptive use still occurs, nations sharing this resource should implement
      scientifically based limits on exploitation to ensure sustainability and mitigate
      impacts to regional population diversity. 

PMID- 24740257
TI  - Potent and specific antitumor effect of CEA-targeted photoimmunotherapy.
AB  - Conventional photodynamic therapy (PDT) for cancer is limited by the insufficient
      efficacy and specificity of photosensitizers. We herein describe a highly
      effective and selective tumor-targeted PDT using a near-infrared (NIR)
      photosensitizer, IRDye700DX, conjugated to a human monoclonal antibody (Ab)
      specific for carcinoembryonic antigen (CEA). The antitumor effects of this Ab
      assisted PDT, called photoimmunotherapy (PIT), were investigated in vitro and in
      vivo. The Ab-IRDye conjugate induced potent cytotoxicity against CEA-positive
      tumor cells after NIR-irradiation, whereas CEA-negative cells were not affected
      at all, even in the presence of excess photoimmunoconjugate. We found an
      equivalent phototoxicity and a predominant plasma membrane localization of Ab
      IRDye after both one and six hours of incubation. Either no or little caspase
      activation and membrane peroxidation were observed in PIT-treated cells and a
      panel of scavengers for reactive oxygen species showed only partial inhibition of
      the phototoxic effect. Strikingly, Ab-IRDye retained significant phototoxicity
      even under hypoxia. We established a xenograft model, which allowed us to
      sensitively investigate the therapeutic efficacy of PIT by non-invasive
      bioluminescence imaging. Luciferase-expressing MKN-45-luc human gastric carcinoma
      cells were subcutaneously implanted into both flanks of nude mice. NIR
      irradiation was performed for only the tumor on one side. In vivo imaging and
      measurement of the tumor size revealed that a single PIT treatment, with
      intraperitoneal administration of Ab-IRDye and subsequent NIR-irradiation, caused
      rapid cell death and significant inhibition of tumor growth, but only on the
      irradiated side. Together, these data suggest that Ab-IRDye-mediated PIT has
      great potential as an anticancer therapeutics targeting CEA-positive tumors.

PMID- 24740259
TI  - Robotic versus open partial nephrectomy: a systematic review and meta-analysis.
AB  - OBJECTIVES: To critically review the currently available evidence of studies
      comparing robotic partial nephrectomy (RPN) and open partial nephrectomy (OPN).
      MATERIALS AND METHODS: A comprehensive review of the literature from Pubmed, Web
      of Science and Scopus was performed in October 2013. All relevant studies
      comparing RPN with OPN were included for further screening. A cumulative meta
      analysis of all comparative studies was performed and publication bias was
      assessed by a funnel plot. RESULTS: Eight studies were included for the analysis,
      including a total of 3418 patients (757 patients in the robotic group and 2661
      patients in the open group). Although RPN procedures had a longer operative time
      (weighted mean difference [WMD]: 40.89; 95% confidence interval [CI], 14.39
      67.40; p = 0.002), patients in this group benefited from a lower perioperative
      complication rate (19.3% for RPN and 29.5% for OPN; odds ratio [OR]: 0.53; 95%CI,
      0.42-0.67; p<0.00001), shorter hospital stay (WMD: -2.78; 95%CI, -3.36 to -1.92;
      p<0.00001), less estimated blood loss(WMD: -106.83; 95%CI, -176.4 to -37.27; p =
      0.003). Transfusions, conversion to radical nephrectomy, ischemia time and
      estimated GFR change, margin status, and overall cost were comparable between the
      two techniques. The main limitation of the present meta-analysis is the non
      randomization of all included studies. CONCLUSIONS: RPN appears to be an
      efficient alternative to OPN with the advantages of a lower rate of perioperative
      complications, shorter length of hospital stay and less blood loss. Nevertheless,
      high quality prospective randomized studies with longer follow-up period are
      needed to confirm these findings.

PMID- 24740260
TI  - The progeroid phenotype of Ku80 deficiency is dominant over DNA-PKCS deficiency.
AB  - Ku80 and DNA-PKCS are both involved in the repair of double strand DNA breaks via
      the nonhomologous end joining (NHEJ) pathway. While ku80-/- mice exhibit a
      severely reduced lifespan and size, this phenotype is less pronounced in dna-pkcs
      /- mice. However, these observations are based on independent studies with
      varying genetic backgrounds. Here, we generated ku80-/-, dna-pkcs-/- and double
      knock out mice in a C57Bl6/J*FVB F1 hybrid background and compared their
      lifespan, end of life pathology and mutation frequency in liver and spleen using
      a lacZ reporter. Our data confirm that inactivation of Ku80 and DNA-PKCS causes
      reduced lifespan and bodyweights, which is most severe in ku80-/- mice. All
      mutant mice exhibited a strong increase in lymphoma incidence as well as other
      aging-related pathology (skin epidermal and adnexal atrophy, trabacular bone
      reduction, kidney tubular anisokaryosis, and cortical and medullar atrophy) and
      severe lymphoid depletion. LacZ mutation frequency analysis did not show strong
      differences in mutation frequencies between knock out and wild type mice. The
      ku80-/- mice had the most severe phenotype and the Ku80-mutation was dominant
      over the DNA-PKCS-mutation. Presumably, the more severe degenerative effect of
      Ku80 inactivation on lifespan compared to DNA-PKCS inactivation is caused by
      additional functions of Ku80 or activity of free Ku70 since both Ku80 and DNA
      PKCS are essential for NHEJ. 

PMID- 24740261
TI  - CDP++.Italian: modelling sublexical and supralexical inconsistency in a shallow
      orthography.
AB  - Most models of reading aloud have been constructed to explain data in relatively
      complex orthographies like English and French. Here, we created an Italian
      version of the Connectionist Dual Process Model of Reading Aloud (CDP++) to
      examine the extent to which the model could predict data in a language which has
      relatively simple orthography-phonology relationships but is relatively complex
      at a suprasegmental (word stress) level. We show that the model exhibits good
      quantitative performance and accounts for key phenomena observed in naming
      studies, including some apparently contradictory findings. These effects include
      stress regularity and stress consistency, both of which have been especially
      important in studies of word recognition and reading aloud in Italian. Overall,
      the results of the model compare favourably to an alternative connectionist model
      that can learn non-linear spelling-to-sound mappings. This suggests that CDP++ is
      currently the leading computational model of reading aloud in Italian, and that
      its simple linear learning mechanism adequately captures the statistical
      regularities of the spelling-to-sound mapping both at the segmental and supra
      segmental levels. 

PMID- 24740262
TI  - Prenatal organophosphates exposure alternates the cleavage plane orientation of
      apical neural progenitor in developing neocortex.
AB  - Prenatal organophosphate exposure elicits long-term brain cytoarchitecture and
      cognitive function impairments, but the mechanism underlying the onset and
      development of neural progenitors remain largely unclear. Using precise
      positioned brain slices, we observed an alternated cleavage plane bias that
      emerged in the mitotic neural progenitors of embryonal neocortex with diazinion
      (DZN) and chlorpyrifos (CPF) pretreatment. In comparison with the control, DZN
      and CPF treatment induced decrease of vertical orientation, increase of oblique
      orientation, and increase of horizontal orientation. That is, the cleavage plane
      orientation bias had been rotated from vertical to horizontal after DZN and CPF
      treatment. Meanwhile, general morphology and mitotic index of the progenitors
      were unchanged. Acephate (ACP), another common organophosphate, had no
      significant effects on the cleavage plane orientation, cell morphology and
      mitotic index. These results represent direct evidence for the toxicity mechanism
      in onset multiplication of neural progenitors. 

PMID- 24740263
TI  - The risk of disease to great apes: simulating disease spread in orang-utan (Pongo
      pygmaeus wurmbii) and chimpanzee (Pan troglodytes schweinfurthii) association
      networks.
AB  - All great ape species are endangered, and infectious diseases are thought to pose
      a particular threat to their survival. As great ape species vary substantially in
      social organisation and gregariousness, there are likely to be differences in
      susceptibility to disease types and spread. Understanding the relation between
      social variables and disease is therefore crucial for implementing effective
      conservation measures. Here, we simulate the transmission of a range of diseases
      in a population of orang-utans in Sabangau Forest (Central Kalimantan) and a
      community of chimpanzees in Budongo Forest (Uganda), by systematically varying
      transmission likelihood and probability of subsequent recovery. Both species have
      fission-fusion social systems, but differ considerably in their level of
      gregariousness. We used long-term behavioural data to create networks of
      association patterns on which the spread of different diseases was simulated. We
      found that chimpanzees were generally far more susceptible to the spread of
      diseases than orang-utans. When simulating different diseases that varied widely
      in their probability of transmission and recovery, it was found that the
      chimpanzee community was widely and strongly affected, while in orang-utans even
      highly infectious diseases had limited spread. Furthermore, when comparing the
      observed association network with a mean-field network (equal contact probability
      between group members), we found no major difference in simulated disease spread,
      suggesting that patterns of social bonding in orang-utans are not an important
      determinant of susceptibility to disease. In chimpanzees, the predicted size of
      the epidemic was smaller on the actual association network than on the mean-field
      network, indicating that patterns of social bonding have important effects on
      susceptibility to disease. We conclude that social networks are a potentially
      powerful tool to model the risk of disease transmission in great apes, and that
      chimpanzees are particularly threatened by infectious disease outbreaks as a
      result of their social structure. 

PMID- 24740264
TI  - Analysis on the relevance of asthma susceptibility with the alteration of
      integrin beta 4 expression.
AB  - Accumulated research has suggested the importance of the adhesion molecules
      modulation as therapeutic approach for bronchial asthma. Adhesion molecules
      expression alteration contributes to the pathogenesis of asthma. In order to
      probe the roles of expression imbalance of adhesion molecules in asthma
      pathogenesis, expression profiling of adhesion molecules was performed using cDNA
      microarray assay. The results showed that the expression pattern of adhesion
      molecules was altered in peripheral blood leucocytes of asthma patients. In this
      study, we focused on one of the abnormally expressed molecule, integrin beta4,
      which was down-regulated in all asthma patients, to analyze the relevance of
      asthma susceptibility with the alteration of integrin beta4 expressions. Real
      time PCR was used to verify the down-regulation of integrin beta4 in additional
      38 asthma patients. Next, the 5'flanking region of integrin beta4 DNA were
      amplified, sequenced and site-directed mutagenesis technology in correspondent
      variation sites were carried out. Among 4 variation sites found in 5' flanking
      region of integrin beta4, 3 were related to asthma susceptibility: -nt1029 G/A, 
      nt 1051 G/A, and -nt 1164 G/C. A reduction of human integrin beta4 promoter
      activity was observed at mutants of these sites. This study demonstrates that
      various adhesion molecules in asthma patients are abnormally expressed. Mutations
      in 5' flanking region result in reduced integrin beta4 expression, which is
      related to increased risk of asthma. 

PMID- 24740265
TI  - Persistent, long-term cerebral white matter changes after sports-related
      repetitive head impacts.
AB  - INTRODUCTION: Repetitive head impacts (RHI) sustained in contact sports are
      thought to be necessary for the long-term development of chronic traumatic
      encephalopathy (CTE). Our objectives were to: 1) characterize the magnitude and
      persistence of RHI-induced white matter (WM) changes; 2) determine their
      relationship to kinematic measures of RHI; and 3) explore their clinical
      relevance. METHODS: Prospective, observational study of 10 Division III college
      football players and 5 non-athlete controls during the 2011-12 season. All
      subjects underwent diffusion tensor imaging (DTI), physiologic, cognitive, and
      balance testing at pre-season (Time 1), post-season (Time 2), and after 6-months
      of no-contact rest (Time 3). Head impact measures were recorded using helmet
      mounted accelerometers. The percentage of whole-brain WM voxels with significant
      changes in fractional anisotropy (FA) and mean diffusivity (MD) from Time 1 to 2,
      and Time 1 to 3 was determined for each subject and correlated to head impacts
      and clinical measures. RESULTS: Total head impacts for the season ranged from 431
      1,850. No athlete suffered a clinically evident concussion. Compared to controls,
      athletes experienced greater changes in FA and MD from Time 1 to 2 as well as
      Time 1 to 3; most differences at Time 2 persisted to Time 3. Among athletes, the
      percentage of voxels with decreased FA from Time 1 to 2 was positively correlated
      with several helmet impact measures. The persistence of WM changes from Time 1 to
      3 was also associated with changes in serum ApoA1 and S100B autoantibodies. WM
      changes were not consistently associated with cognition or balance. CONCLUSIONS:
      A single football season of RHIs without clinically-evident concussion resulted
      in WM changes that correlated with multiple helmet impact measures and persisted
      following 6 months of no-contact rest. This lack of WM recovery could potentially
      contribute to cumulative WM changes with subsequent RHI exposures.

PMID- 24740267
TI  - The key role of -CH3 steric hindrance in bis(pyrazolyl) ligand on polyoxometalate
      based compounds.
AB  - Through using two kinds of bis(pyrazolyl) ligands, four polyoxometalate (POM)
      based compounds were hydrothermally synthesized and structurally characterized,
      [Ag3(Hbhpe)2(H2O)(H2PMo12O40)].H2O (1), [Ag(H2bdpm)2(H2PW12O40)].4H2O (2),
      [Ag6(H2bdpm)6(HPW(VI)8W(V)4O40)].2H2O (2) and [Ag4(H2bdpm)4(H2P2W18O62)].3H2O (4)
      (H2bhpe = 1,2-bis(1-H-pyrazolate)ethane, H2bdpm = 1,1'-bis(3,5-dimethyl-1H
      pyrazolate)methane). In compound 1, the Ag-Hbhpe subunit is a 2D layer containing
      large penta-membered cycles and small tri-nuclear Ag(I) clusters. The Keggin
      anions covalently float on the large cycles. In compound 2, the Keggin anions are
      fused by [Ag(H2bdpm)2](+) subunits to form a 1D chain. Compound contains hexa
      membered metal-organic cycles, which are further linked by Keggin anions to build
      a 1D chain. Adjacent chains share the Ag(I) ions to construct a 3D framework of
      3. Compound 4 exhibits a wavy double-track chain structure, with the Wells-Dawson
      anions covalently suspended up and down this chain. The steric hindrance of -CH3
      groups in H2bdpm leads to the formation of mono-nuclear Ag(I) subunits in 2 - 4.
      The influence of -CH3 steric hindrance in bis(pyrazolyl) ligands on the
      structures of 1 - 4 is discussed. The electrochemical and photocatalytic
      properties of the title compounds have been studied.

PMID- 24740266
TI  - Embryonic protein undernutrition by albumen removal programs the hepatic amino
      acid and glucose metabolism during the perinatal period in an avian model.
AB  - Different animal models have been used to study the effects of prenatal protein
      undernutrition and the mechanisms by which these occur. In mammals, the maternal
      diet is manipulated, exerting both direct nutritional and indirect hormonal
      effects. Chicken embryos develop independent from the hen in the egg. Therefore,
      in the chicken, the direct effects of protein deficiency by albumen removal early
      during incubation can be examined. Prenatal protein undernutrition was
      established in layer-type eggs by the partial replacement of albumen by saline at
      embryonic day 1 (albumen-deprived group), compared to a mock-treated sham and a
      non-treated control group. At hatch, survival of the albumen-deprived group was
      lower compared to the control and sham group due to increased early mortality by
      the manipulation. No treatment differences in yolk-free body weight or yolk
      weight could be detected. The water content of the yolk was reduced, whereas the
      water content of the carcass was increased in the albumen-deprived group,
      compared to the control group, indicating less uptake of nutrients from the yolk.
      At embryonic day 16, 20 and at hatch, plasma triiodothyronine (T3),
      corticosterone, lactate or glucose concentrations and hepatic glycogen content
      were not affected by treatment. At embryonic day 20, the plasma thyroxine (T4)
      concentrations of the albumen-deprived embryos was reduced compared to the
      control group, indicating a decreased metabolic rate. Screening for differential
      protein expression in the liver at hatch using two-dimensional difference gel
      electrophoresis revealed not only changed abundance of proteins important for
      amino acid metabolism, but also of enzymes related to energy and glucose
      metabolism. Interestingly, GLUT1, a glucose transporter, and PCK2 and FBP1, two
      out of three regulatory enzymes of the gluconeogenesis were dysregulated. No
      parallel differences in gene expressions causing the differences in protein
      abundance could be detected pointing to post-transcriptional or post
      translational regulation of the observed differences. 

PMID- 24740268
TI  - Phase I trial of everolimus, gemcitabine and cisplatin in patients with solid
      tumors.
AB  - BACKGROUND: A Phase I trial of the 2-drug regimen of everolimus plus gemcitabine
      (Cohort I) and the 3-drug regimen of everolimus plus gemcitabine and cisplatin
      (Cohort II) was performed to determine the maximally tolerated dose (MTD) of both
      combinations. An expansion cohort (Cohort III) of patients with
      cholangiocarcinoma or gallbladder carcinoma was treated at the MTD. METHODS: A
      standard 3 + 3 design dose escalation was used. Everolimus was given on
      Monday/Wednesday/Friday or daily depending upon the dose level. Gemcitabine and
      cisplatin were administered on days 1 and 8 of each 21 day cycle. RESULTS: Twelve
      patients were entered in Cohort I and 15 in Cohort II. The MTD for Cohort I was
      everolimus 5 mg on Monday/Wednesday/Friday and gemcitabine 800 mg/m(2). For
      Cohort II, it was everolimus 5 mg on Monday/Wednesday/Friday, gemcitabine 600
      mg/m(2), and cisplatin 12.5 mg/m(2). All DLTs in this study were hematologic.
      Complete responses (CR) were seen in a patient with primary peritoneal carcinoma
      and another with recurrent pancreatic cancer. Partial responses (PR) were seen in
      3 patients: breast, ampullary carcinoma and pheochromocytoma. Of 10 patients
      enrolled in Cohort III, six patients had stable disease and 4 had progressive
      disease. CONCLUSIONS: This Phase I clinical trial has demonstrated that these 2
      drug and 3-drug combinations are generally well tolerated and safely
      administered. The main DLTs in both regimens were hematologic, specifically
      thrombocytopenia. The 3-drug combination can be considered as a platform for
      future studies in specific tumor types.

PMID- 24740269
TI  - Oxidative post-translational modifications develop LONP1 dysfunction in pressure
      overload heart failure.
AB  - BACKGROUND: Mitochondrial compromise is a fundamental contributor to heart
      failure. Recent studies have revealed that several surveillance systems maintain
      mitochondrial integrity. The present study evaluated the role of mitochondrial
      AAA+ protease in a mouse model of pressure overload heart failure. METHODS AND
      RESULTS: The fluorescein isothiocyanate casein assay and immunoblotting for
      endogenous mitochondrial proteins revealed a marked reduction in ATP-dependent
      proteolytic activity in failing heart mitochondria. The level of reduced cysteine
      was decreased, and tyrosine nitration and protein carbonylation were promoted in
      Lon protease homolog (LONP1), the most abundant mitochondrial AAA+ protease, in
      heart failure. Comprehensive analysis revealed that electron transport chain
      protein levels were increased even with a reduction in the expression of their
      corresponding mRNAs in heart failure, which indicated decreased protein turnover
      and resulted in the accumulation of oxidative damage in the electron transport
      chain. The induction of mitochondria-targeted human catalase ameliorated
      proteolytic activity and protein homeostasis in the electron transport chain,
      leading to improvements in mitochondrial energetics and cardiac contractility
      even during the late stage of pressure overload. Moreover, the infusion of
      mitoTEMPO, a mitochondria-targeted superoxide dismutase mimetic, recovered
      oxidative modifications of LONP1 and improved mitochondrial respiration capacity
      and cardiac function. The in vivo small interfering RNA repression of LONP1
      partially canceled the protective effects of mitochondria-targeted human catalase
      induction and mitoTEMPO infusion. CONCLUSIONS: Oxidative post-translational
      modifications attenuate mitochondrial AAA+ protease activity, which is involved
      in impaired electron transport chain protein homeostasis, mitochondrial
      respiration deficiency, and left ventricular contractile dysfunction. Oxidatively
      inactivated proteases may be an endogenous target for mitoTEMPO treatment in
      pressure overload heart failure.

PMID- 24740270
TI  - Dual-color imaging of cytosolic and mitochondrial zinc ions in live tissues with
      two-photon fluorescent probes.
AB  - We report two-photon probes for Zn(2+) ions that can simultaneously detect
      cytosolic and mitochondrial Zn(2+) ions in live cells and living tissues at 115
      mm depth by dual-color TPM imaging with minimum interference from other
      biologically relevant species. 

PMID- 24740271
TI  - Surgical management of urolithiasis in spinal cord injury patients.
AB  - Urolithiasis is a common condition in patients with spinal cord injury (SCI).
      Surgical management of stones in this population is more challenging and
      associated with lower clearance rates than the general population. The rate of
      complications - specifically infectious complications - is also high due to the
      chronic bacterial colonization. Shock wave lithotripsy (SWL) has a low clearance
      rate of 44-73 %. Percutaneous nephrolithotripsy is indicated for larger
      nephrolithiasis, but multiple procedures may be required to clear the stones.
      Ureteroscopy has been associated with low success rates because of difficulty in
      obtaining ureteral access. Historically, bladder stones were managed with open
      surgery or SWL. Recently, good results have been reported with the combination of
      endoscopic and laparoscopic techniques. Surgical management of urolithiasis in
      patients with SCI should be performed in high-volume centers in light of the
      technical challenges and higher rate of perioperative complications.

PMID- 24740272
TI  - Significance of biofilm for the prosthetic surgeon.
AB  - Biofilm formation on implanted medical devices is becoming more recognized as
      both a common finding and a potential problem. Although seen frequently in
      nature, these sequestered bacterial communities are proving to be an assiduous
      enemy as medical device technologies advance. The penile prosthesis has gone
      through many improvements, now with a more reliable mechanical function and a
      reduced infection rate. However, there remains a notable increase in infectious
      risk in revisions compared to novel cases, with many implants found to harbor a
      subclinical bacterial presence isolated in biofilms. This article focuses on
      recent updates in implant technology and surgical technique to combat infection,
      and reviews current research on biofilm prevention and treatment. 

PMID- 24740273
TI  - Current management of penile implant infections, device reliability, and
      optimizing cosmetic outcome.
AB  - Penile implants hold a major position in the treatment algorithm for patients
      with erectile dysfunction who find medications and vacuum erection devices
      ineffective or unsatisfactory. As with any surgical procedure, adverse events may
      occur. The infection rate associated with implant placement has been lowered to
      the range of 1 % or less due to multifactorial improvements including no-touch
      techniques, the use of antibiotic-coated devices, and improved quality measures
      in the operating room. Urologists have been proactive in employing techniques and
      procedures which minimize loss of erectile length, hence enhancing patient
      satisfaction. Flat reservoirs have been developed and techniques of placing these
      to avoid problems in the space of Retzius have reduced complication rates as
      well. Device reliability has improved to the point that penile implants are among
      the most durable mechanical surgical products that contribute to patient and
      partner satisfaction, which is by far the greatest among all the treatments of
      erectile dysfunction.

PMID- 24740274
TI  - Interventional radiologic techniques for screening, diagnosis and treatment of
      patients with renal artery stenosis.
AB  - Renal artery stenosis resulting in renovascular hypertension or renal ischemia is
      a potentially treatable condition that results in increased morbidity and
      mortality, especially among older individuals. Sophisticated imaging techniques
      are used for screening and identification of affected patients to guide therapy.
      Treatment guidelines recommend intervention in patients with significant renal
      artery stenosis, although recent evidence has questioned the benefit of
      intervention in certain populations. Current research focuses on improving the
      specificity of imaging techniques and determining which imaging modalities best
      identify patients who will benefit from intervention. 

PMID- 24740276
TI  - De novo peptide design and experimental validation of histone methyltransferase
      inhibitors.
AB  - Histones are small proteins critical to the efficient packaging of DNA in the
      nucleus. DNA-protein complexes, known as nucleosomes, are formed when the DNA
      winds itself around the surface of the histones. The methylation of histone
      residues by enhancer of zeste homolog 2 (EZH2) maintains gene repression over
      successive cell generations. Overexpression of EZH2 can silence important tumor
      suppressor genes leading to increased invasiveness of many types of cancers. This
      makes the inhibition of EZH2 an important target in the development of cancer
      therapeutics. We employed a three-stage computational de novo peptide design
      method to design inhibitory peptides of EZH2. The method consists of a sequence
      selection stage and two validation stages for fold specificity and approximate
      binding affinity. The sequence selection stage consists of an integer linear
      optimization model that was solved to produce a rank-ordered list of amino acid
      sequences with increased stability in the bound peptide-EZH2 structure. These
      sequences were validated through the calculation of the fold specificity and
      approximate binding affinity of the designed peptides. Here we report the
      discovery of novel EZH2 inhibitory peptides using the de novo peptide design
      method. The computationally discovered peptides were experimentally validated in
      vitro using dose titrations and mechanism of action enzymatic assays. The peptide
      with the highest in vitro response, SQ037, was validated in nucleo using
      quantitative mass spectrometry-based proteomics. This peptide had an IC50 of 13.5
      mM, demonstrated greater potency as an inhibitor when compared to the native and
      K27A mutant control peptides, and demonstrated competitive inhibition versus the
      peptide substrate. Additionally, this peptide demonstrated high specificity to
      the EZH2 target in comparison to other histone methyltransferases. The validated
      peptides are the first computationally designed peptides that directly inhibit
      EZH2. These inhibitors should prove useful for further chromatin biology
      investigations.

PMID- 24740275
TI  - Update on medical management of Peyronie's disease.
AB  - The treatment of Peyronie's disease (PD) is a challenge for the clinician. In the
      quest to straighten the penis, alleviate pain, prevent further shortening, and
      restore erectile function, many non-surgical treatments have been offered in lieu
      of an operative approach, which is still considered the gold standard for
      definitive treatment. This communication is an update on the different approaches
      used in the minimally invasive management of this frustrating and yet intriguing
      condition. 

PMID- 24740277
TI  - Nickel-resistance determinants in Acidiphilium sp. PM identified by genome-wide
      functional screening.
AB  - Acidiphilium spp. are conspicuous dwellers of acidic, metal-rich environments.
      Indeed, they are among the most metal-resistant organisms; yet little is known
      about the mechanisms behind the metal tolerance in this genus. Acidiphilium sp.
      PM is an environmental isolate from Rio Tinto, an acidic, metal-laden river
      located in southwestern Spain. The characterization of its metal resistance
      revealed a remarkable ability to tolerate high Ni concentrations. Here we report
      the screening of a genomic library of Acidiphilium sp. PM to identify genes
      involved in Ni resistance. This approach revealed seven different genes
      conferring Ni resistance to E. coli, two of which form an operon encoding the ATP
      dependent protease HslVU (ClpQY). This protease was found to enhance resistance
      to both Ni and Co in E. coli, a function not previously reported. Other Ni
      resistance determinants include genes involved in lipopolysaccharide biosynthesis
      and the synthesis of branched amino acids. The diversity of molecular functions
      of the genes recovered in the screening suggests that Ni resistance in
      Acidiphilium sp. PM probably relies on different molecular mechanisms. 

PMID- 24740278
TI  - The positive effects of priming exercise on oxygen uptake kinetics and high
      intensity exercise performance are not magnified by a fast-start pacing strategy
      in trained cyclists.
AB  - The purpose of this study was to determine both the independent and additive
      effects of prior heavy-intensity exercise and pacing strategies on the VO2
      kinetics and performance during high-intensity exercise. Fourteen endurance
      cyclists (VO2max  = 62.8 +/- 8.5 mL.kg-1.min-1) volunteered to participate in the
      present study with the following protocols: 1) incremental test to determine
      lactate threshold and VO2max; 2) four maximal constant-load tests to estimate
      critical power; 3) six bouts of exercise, using a fast-start (FS), even-start
      (ES) or slow-start (SS) pacing strategy, with and without a preceding heavy
      intensity exercise session (i.e., 90% critical power). In all conditions, the
      subjects completed an all-out sprint during the final 60 s of the test as a
      measure of the performance. For the control condition, the mean response time was
      significantly shorter (p < 0.001) for FS (27 +/- 4 s) than for ES (32 +/- 5 s)
      and SS (32 +/- 6 s). After the prior exercise, the mean response time was not
      significantly different among the paced conditions (FS = 24 +/- 5 s; ES = 25 +/-
      5 s; SS = 26 +/- 5 s). The end-sprint performance (i.e., mean power output) was
      only improved (~ 3.2%, p<0.01) by prior exercise. Thus, in trained endurance
      cyclists, an FS pacing strategy does not magnify the positive effects of priming
      exercise on the overall VO2 kinetics and short-term high-intensity performance.

PMID- 24740279
TI  - The effect of noggin interference in a rabbit posterolateral spinal fusion model.
AB  - STUDY DESIGN: Noggin protein levels and spinal fusion rates were compared in a
      rabbit model after application of siRNA against BMP antagonist noggin in
      paraspinal muscle. OBJECTIVE: To test whether endogenous BMPs are sufficient to
      form bone in the absence of their antagonists, using noggin siRNA to interrupt
      the negative feedback loop on endogenous BMP within the paraspinal muscles in
      rabbits. Unused Posterolateral lumbar fusion is a standard surgical treatment for
      many spinal disorders, yet even under ideal conditions the rate of non-fusion
      approaches 25 %. BMPs are effective in promoting bone formation, and are
      inhibited by antagonists such as noggin. We have previously shown that in this
      model, endogenous BMPs are present and endogenous BMP antagonist noggin is
      strongly increased during spinal fusion. Previous studies have found that noggin
      siRNA enhanced spinal fusion in combination with supra-physiological amounts of
      exogenous BMP; however, the effect of the siRNA alone remains unknown. METHODS: A
      posterolateral intertransverse rabbit lumbar fusion was utilized, as established
      by Boden et al. SiRNA against noggin was electroporated into paraspinal muscle to
      determine its effect on fusion. Outcome measures included noggin protein
      expression, and assessment of spinal fusion at 6 weeks. RESULTS: SiRNAs were
      effective in reducing overexpressed noggin in vitro. Noggin protein was
      successfully knocked down in vivo for the initial 7 days in our rabbit model and
      returned to detectable levels by 4 weeks and to normal levels by 6 weeks. The
      overall fusion rate was not significantly enhanced compared to established
      controls from our earlier work (Tang et al.). CONCLUSIONS: Early noggin
      suppression does not appear to enhance the BMP activity sufficiently to
      significantly affect final fusion rates in our model.

PMID- 24740280
TI  - Comparison of blood loss according to use of aspirin in lumbar fusion patients.
AB  - OBJECTIVE: To investigate and compare blood losses intra and postoperatively
      between lumbar fusion patients with and without antiplatelet use. METHODS: A
      total of 106 patients who had undergone at least 2 or more segments of lumbar
      fusion surgery were selected for the study. They were divided into three groups.
      Group 1 was not on medication before the surgery. Groups 2 and 3 had taken
      aspirin prior to the surgery. Group 2 discontinued the medication 1 week before
      the operation, but group 3 continued the use. In addition, non-steroid anti
      inflammatory drug (NSAIDs) use in all patients was questioned. Amount of blood
      losses and platelet function were evaluated. RESULTS: When usage of NSAID was not
      controlled, intraoperative, postoperative, and total blood losses were found to
      have no statistical significance among the groups. However, when NSAID usage was
      taken into account, there were significantly higher blood losses in groups 2 and
      3 compared with group 1. The use of NSAID resulted in significantly higher blood
      loss in group 1, but not in groups 2 or 3. The platelet function test results
      disclosed statistical differences between groups 1 and 2 and groups 1 and 3.
      CONCLUSION: Aspirin significantly increases the risk of bleeding in patients
      undergoing lumbar fusion at two or more levels. This risk is present even in
      patients who discontinued aspirin 1 week prior to surgery. In patients with high
      risk of complications resulting from aspirin discontinuation, the use should be
      allowed in lumbar fusion surgery. However, strong attention must be paid to avoid
      excessive bleeding. Because NSAID use also increases surgical blood loss, proper
      interval from discontinuation to surgery must be granted to minimize the risk.

PMID- 24740281
TI  - Two different scenarios of squamous cell carcinoma within advanced Basal cell
      carcinomas: cases illustrating the importance of serial biopsy during vismodegib
      usage.
AB  - IMPORTANCE: Vismodegib is a Hedgehog signaling pathway inhibitor recently
      approved by the US Food and Drug Administration for advanced basal cell
      carcinoma. We present 2 cases of clinically significant squamous cell carcinoma
      within the tumor bed of locally advanced basal cell carcinoma found during
      vismodegib treatment. OBSERVATIONS: The first case is that of a patient with
      locally advanced basal cell carcinoma responsive to vismodegib but with an
      enlarging papule within the tumor bed. On biopsy, this papule was an invasive
      acantholytic squamous cell carcinoma. The second case is that of a patient with
      Gorlin syndrome with a locally advanced basal cell carcinoma that was stable
      while the patient was receiving therapy with vismodegib for 2.5 years but
      subsequently increased in size. Biopsy specimens from this tumor showed invasive
      squamous cell carcinoma, spindle cell subtype. In both cases, the squamous cell
      carcinomas were surgically resected. CONCLUSIONS AND RELEVANCE: These cases
      highlight the importance of repeated biopsy in locally advanced basal cell
      carcinomas in 2 clinical situations: (1) when an area within the tumor responds
      differentially to vismodegib, and (2) when a tumor stops being suppressed by
      vismodegib. Timely diagnosis of non-basal cell histologic characteristics is
      critical to institution of effective therapy.

PMID- 24740282
TI  - The effect of urban basic medical insurance on health service utilisation in
      Shaanxi Province, China: a comparison of two schemes.
AB  - BACKGROUND: Urban population in China is mainly covered by two medical insurance
      schemes: the Urban Employee Basic Medical Insurance (UEBMI) for urban employees
      in formal sector and the Urban Resident Basic Medical Insurance (URBMI) for the
      left urban residents, mainly the unemployed, the elderly and children. This paper
      studies the effects of UEBMI and URBMI on health services utilisation in Shaanxi
      Province, Western China. METHODS: Cross-sectional data from the 4th National
      Health Services Survey - Shaanxi Province was studied. The propensity score
      matching and the coarsened exact matching methods have been used to estimate the
      average medical insurance effect on the insured. RESULTS: Compared to the
      uninsured, robust results suggest that UEBMI had significantly increased the
      outpatient health services utilisation in the last two weeks (p<0.10), whilst the
      significant effect on hospitalisation was evident in the CEM method (p<0.10). The
      effect of URBMI was limited in that although being insured was associated with
      higher health services utilisation, compared with the uninsured, none of the
      improvement was statistically significant (p>0.10). It was also found that
      compared with the uninsured, basic medical insurance enrollees were more likely
      to purchase inpatient treatments in lower levels of hospitals, consistent with
      the incentive of the benefit package design. CONCLUSION: Basic Medical insurance
      schemes have shown a positive but limited effect on increasing health services
      utilisation in Shaanxi Province. The benefit package design of higher
      reimbursement rates for lower level hospitals has induced the insured to use
      medical services in lower level hospitals for inpatient services.

PMID- 24740283
TI  - Chimpanzees preferentially select sleeping platform construction tree species
      with biomechanical properties that yield stable, firm, but compliant nests.
AB  - The daily construction of a sleeping platform or "nest" is a universal behavior
      among large-bodied hominoids. Among chimpanzees, most populations consistently
      select particular tree species for nesting, yet the principles that guide species
      preferences are poorly understood. At Semliki, Cynometra alexandri constitutes
      only 9.6% of all trees in the gallery forest in which the study populations
      ranges, but it was selected for 73.6% of the 1,844 chimpanzee night beds we
      sampled. To determine whether physical properties influence nesting site
      selection, we measured the physical characteristics of seven common tree species
      at the Toro-Semliki Wildlife Reserve, Uganda. We determined stiffness and bending
      strength for a sample of 326 branches from the seven most commonly used tree
      species. We selected test-branches with diameters typically used for nest
      construction. We measured internode distance, calculated mean leaf surface area
      (cm2) and assigned a tree architecture category to each of the seven species. C.
      alexandri fell at the extreme of the sample for all four variables and shared a
      tree architecture with only one other of the most commonly selected species. C.
      alexandri was the stiffest and had the greatest bending strength; it had the
      smallest internode distance and the smallest leaf surface area. C. alexandri and
      the second most commonly selected species, Cola gigantea, share a 'Model of
      Koriba' tree architecture. We conclude that chimpanzees are aware of the
      structural properties of C. alexandri branches and choose it because its
      properties afford chimpanzees sleeping platforms that are firm, stable and
      resilient. 

PMID- 24740284
TI  - Traffic experiment reveals the nature of car-following.
AB  - As a typical self-driven many-particle system far from equilibrium, traffic flow
      exhibits diverse fascinating non-equilibrium phenomena, most of which are closely
      related to traffic flow stability and specifically the growth/dissipation pattern
      of disturbances. However, the traffic theories have been controversial due to a
      lack of precise traffic data. We have studied traffic flow from a new perspective
      by carrying out large-scale car-following experiment on an open road section,
      which overcomes the intrinsic deficiency of empirical observations. The
      experiment has shown clearly the nature of car-following, which runs against the
      traditional traffic flow theory. Simulations show that by removing the
      fundamental notion in the traditional car-following models and allowing the
      traffic state to span a two-dimensional region in velocity-spacing plane, the
      growth pattern of disturbances has changed qualitatively and becomes
      qualitatively or even quantitatively in consistent with that observed in the
      experiment. 

PMID- 24740285
TI  - Computer simulation of magnetic resonance angiography imaging: model description
      and validation.
AB  - With the development of medical imaging modalities and image processing
      algorithms, there arises a need for methods of their comprehensive quantitative
      evaluation. In particular, this concerns the algorithms for vessel tracking and
      segmentation in magnetic resonance angiography images. The problem can be
      approached by using synthetic images, where true geometry of vessels is known.
      This paper presents a framework for computer modeling of MRA imaging and the
      results of its validation. A new model incorporates blood flow simulation within
      MR signal computation kernel. The proposed solution is unique, especially with
      respect to the interface between flow and image formation processes. Furthermore
      it utilizes the concept of particle tracing. The particles reflect the flow of
      fluid they are immersed in and they are assigned magnetization vectors with
      temporal evolution controlled by MR physics. Such an approach ensures flexibility
      as the designed simulator is able to reconstruct flow profiles of any type. The
      proposed model is validated in a series of experiments with physical and digital
      flow phantoms. The synthesized 3D images contain various features (including
      artifacts) characteristic for the time-of-flight protocol and exhibit remarkable
      correlation with the data acquired in a real MR scanner. The obtained results
      support the primary goal of the conducted research, i.e. establishing a reference
      technique for a quantified validation of MR angiography image processing
      algorithms. 

PMID- 24740286
TI  - Multiple consecutive infections might explain the lack of protection by BCG.
AB  - Although contacts between tuberculosis patients may result in multiple
      consecutive infections (MCI), no experimental animal models consider this fact
      when used in basic studies. Moreover, the current TB vaccine (BCG) has
      demonstrated a limited protection in humans. In this study we evaluate the effect
      of tuberculosis MCI by way of a simple mathematical analysis using data from the
      low dose aerosol murine experimental model. The results show that a higher number
      of, or shorter intervals between, multiple consecutive infections reduce the
      protective effect of BCG. This is due to both the increase in bacillary load at
      the stationary level of the infection, and the protective immune response induced
      by the infection itself. This factor must therefore be taken into account when
      designing new prophylactic strategies as candidate vaccines for the replacement
      of BCG. 

PMID- 24740287
TI  - Mutant TDP-43 deregulates AMPK activation by PP2A in ALS models.
AB  - Bioenergetic abnormalities and metabolic dysfunction occur in amyotrophic lateral
      sclerosis (ALS) patients and genetic mouse models. However, whether metabolic
      dysfunction occurs early in ALS pathophysiology linked to different ALS genes
      remains unclear. Here, we investigated AMP-activated protein kinase (AMPK)
      activation, which is a key enzyme induced by energy depletion and metabolic
      stress, in neuronal cells and mouse models expressing mutant superoxide dismutase
      1 (SOD1) or TAR DNA binding protein 43 (TDP-43) linked to ALS. AMPK
      phosphorylation was sharply increased in spinal cords of transgenic SOD1G93A mice
      at disease onset and accumulated in cytoplasmic granules in motor neurons, but
      not in presymptomatic mice. AMPK phosphorylation also occurred in peripheral
      tissues, liver and kidney, in SOD1G93A mice at disease onset, demonstrating that
      AMPK activation occurs late and is not restricted to motor neurons. Conversely,
      AMPK activity was drastically diminished in spinal cords and brains of
      presymptomatic and symptomatic transgenic TDP-43A315T mice and motor neuronal
      cells expressing different TDP-43 mutants. We show that mutant TDP-43 induction
      of the AMPK phosphatase, protein phosphatase 2A (PP2A), is associated with AMPK
      inactivation in these ALS models. Furthermore, PP2A inhibition by okadaic acid
      reversed AMPK inactivation by mutant TDP-43 in neuronal cells. Our results
      suggest that mutant SOD1 and TDP-43 exert contrasting effects on AMPK activation
      which may reflect key differences in energy metabolism and neurodegeneration in
      spinal cords of SOD1G93A and TDP-43A315T mice. While AMPK activation in motor
      neurons correlates with progression in mutant SOD1-mediated disease, AMPK
      inactivation mediated by PP2A is associated with mutant TDP-43-linked ALS.

PMID- 24740288
TI  - Larval dispersal modeling of pearl oyster Pinctada margaritifera following
      realistic environmental and biological forcing in Ahe atoll lagoon.
AB  - Studying the larval dispersal of bottom-dwelling species is necessary to
      understand their population dynamics and optimize their management. The black-lip
      pearl oyster (Pinctada margaritifera) is cultured extensively to produce black
      pearls, especially in French Polynesia's atoll lagoons. This aquaculture relies
      on spat collection, a process that can be optimized by understanding which
      factors influence larval dispersal. Here, we investigate the sensitivity of P.
      margaritifera larval dispersal kernel to both physical and biological factors in
      the lagoon of Ahe atoll. Specifically, using a validated 3D larval dispersal
      model, the variability of lagoon-scale connectivity is investigated against wind
      forcing, depth and location of larval release, destination location, vertical
      swimming behavior and pelagic larval duration (PLD) factors. The potential
      connectivity was spatially weighted according to both the natural and cultivated
      broodstock densities to provide a realistic view of connectivity. We found that
      the mean pattern of potential connectivity was driven by the southwest and
      northeast main barotropic circulation structures, with high retention levels in
      both. Destination locations, spawning sites and PLD were the main drivers of
      potential connectivity, explaining respectively 26%, 59% and 5% of the variance.
      Differences between potential and realistic connectivity showed the significant
      contribution of the pearl oyster broodstock location to its own dynamics.
      Realistic connectivity showed larger larval supply in the western destination
      locations, which are preferentially used by farmers for spat collection. In
      addition, larval supply in the same sectors was enhanced during summer wind
      conditions. These results provide new cues to understanding the dynamics of
      bottom-dwelling populations in atoll lagoons, and show how to take advantage of
      numerical models for pearl oyster management. 

PMID- 24740289
TI  - Impact of plant cover on fitness and behavioural traits of captive red-eyed tree
      frogs (Agalychnis callidryas).
AB  - Despite the importance of ex situ conservation programmes as highlighted in the
      Amphibian Conservation Action Plan, there are few empirical studies that examine
      the influence of captive conditions on the fitness of amphibians, even for basic
      components of enclosure design such as cover provision. Maintaining the fitness
      of captive amphibian populations is essential to the success of ex situ
      conservation projects. Here we examined the impact of plant cover on measures of
      fitness and behaviour in captive red-eyed tree frogs (Agalychnis callidryas). We
      found significant effects of plant provision on body size, growth rates and
      cutaneous bacterial communities that together demonstrate a compelling fitness
      benefit from cover provision. We also demonstrate a strong behavioural preference
      for planted rather than non-planted areas. We also assessed the impact of plant
      provision on the abiotic environment in the enclosure as a potential driver of
      these behavioural and fitness effects. Together this data provides valuable
      information regarding enclosure design for a non-model amphibian species and has
      implications for amphibian populations maintained in captivity for conservation
      breeding programmes and research. 

PMID- 24740290
TI  - Outcomes of acute chest syndrome in adult patients with sickle cell disease:
      predictors of mortality.
AB  - Adults with sickle cell disease(SCD) are a growing population. Recent national
      estimates of outcomes in acute chest syndrome(ACS) among adults with SCD are
      lacking. We describe the incidence, outcomes and predictors of mortality in ACS
      in adults. We hypothesize that any need for mechanical ventilation is an
      independent predictor of mortality. METHODS: We performed a retrospective
      analysis of the Nationwide Inpatient Sample(2004-2010),the largest all payer
      inpatient database in United States, to estimate the incidence and outcomes of
      ACS needing mechanical ventilation(MV) and exchange transfusion(ET) in patients
      >21 years. The effects of MV and ET on outcomes including length of stay(LOS) and
      in-hospital mortality(IHM) were examined using multivariable linear and logistic
      regression models respectively. The effects of age, sex, race, type of sickle
      cell crisis, race, co-morbid burden, insurance status, type of admission, and
      hospital characteristics were adjusted in the regression models. RESULTS: Of the
      24,699 hospitalizations, 4.6% needed MV(2.7% for <96 hours, 1.9% for >=96 hours),
      6% had ET, with a mean length of stay(LOS) of 7.8 days and an in-hospital
      mortality rate(IHM) of 1.6%. There was a gradual yearly increase in ACS
      hospitalizations that needed MV(2.6% in 2004 to 5.8% in 2010). Hb-SS disease was
      the phenotype in 84.3% of all hospitalizations. After adjusting for a multitude
      of patient and hospital related factors, patients who had MV for <96 hours(OR =
      67.53,p<0.01) or those who had MV for >=96 hours(OR = 8.73,p<0.01) were
      associated with a significantly higher odds for IHM when compared to their
      counterparts. Patients who had MV for >=96 hours and those who had ET had a
      significantly longer LOS in-hospitals(p<0.001). CONCLUSION: In this large cohort
      of hospitalized adults with SCD patients with ACS, the need for mechanical
      ventilation predicted higher mortality rates and increased hospital resource
      utilization. Identification of risk factors may enable optimization of outcomes.

PMID- 24740292
TI  - Helios defines T cells being driven to tolerance in the periphery and thymus.
AB  - The expression of the Ikaros transcription factor family member, Helios, has been
      shown to be associated with T-cell tolerance in both the thymus and the
      periphery. To better understand the importance of Helios in tolerance pathways,
      we have examined the expression of Helios in TCR-transgenic T cells specific for
      the gastric H(+) /K(+) ATPase, the autoantigen target in autoimmune gastritis.
      Analysis of H(+) /K(+) ATPase-specific T cells in mice with different patterns of
      H(+) /K(+) ATPase expression revealed that, in addition to the expression of
      Helios in CD4(+) Foxp3(+) regulatory T (Treg) cells, Helios is expressed by a
      large proportion of CD4(+) Foxp3(-) T cells in both the thymus and the
      paragastric lymph node (PgLN), which drains the stomach. In the thymus, Helios
      was expressed by H(+) /K(+) ATPase-specific thymocytes that were undergoing
      negative selection. In the periphery, Helios was expressed in H(+) /K(+) ATPase
      specific CD4(+) T cells following H(+) /K(+) ATPase presentation and was more
      highly expressed when T-cell activation occurred in the absence of inflammation.
      Analysis of purified H(+) /K(+) ATPase-specific CD4(+) Foxp3(-) Helios(+) T cells
      demonstrated that they were functionally anergic. These results demonstrate that
      Helios is expressed by thymic and peripheral T cells that are being driven to
      tolerance in response to a genuine autoantigen. 

PMID- 24740291
TI  - Association of blood lead level with neurological features in 972 children
      affected by an acute severe lead poisoning outbreak in Zamfara State, northern
      Nigeria.
AB  - BACKGROUND: In 2010, Medecins Sans Frontieres (MSF) investigated reports of high
      mortality in young children in Zamfara State, Nigeria, leading to confirmation of
      villages with widespread acute severe lead poisoning. In a retrospective
      analysis, we aimed to determine venous blood lead level (VBLL) thresholds and
      risk factors for encephalopathy using MSF programmatic data from the first year
      of the outbreak response. METHODS AND FINDINGS: We included children aged <=5
      years with VBLL >=45 ug/dL before any chelation and recorded neurological status.
      Odds ratios (OR) for neurological features were estimated; the final model was
      adjusted for age and baseline VBLL, using random effects for village of
      residence. 972 children met inclusion criteria: 885 (91%) had no neurological
      features; 34 (4%) had severe features; 47 (5%) had reported recent seizures; and
      six (1%) had other neurological abnormalities. The geometric mean VBLLs for all
      groups with neurological features were >100 ug/dL vs 65.9 ug/dL for those without
      neurological features. The adjusted OR for neurological features increased with
      increasing VBLL: from 2.75, 95%CI 1.27-5.98 (80-99.9 ug/dL) to 22.95, 95%CI 10.54
      49.96 (>=120 ug/dL). Neurological features were associated with younger age (OR
      4.77 [95% CI 2.50-9.11] for 1-<2 years and 2.69 [95%CI 1.15-6.26] for 2-<3 years,
      both vs 3-5 years). Severe neurological features were seen at VBLL <105 ug/dL
      only in those with malaria. INTERPRETATION: Increasing VBLL (from >=80 ug/dL) and
      age 1-<3 years were strongly associated with neurological features; in those
      tested for malaria, a positive test was also strongly associated. These factors
      will help clinicians managing children with lead poisoning in prioritising
      therapy and developing chelation protocols.

PMID- 24740293
TI  - Identification of selection footprints on the X chromosome in pig.
AB  - Identifying footprints of selection can provide a straightforward insight into
      the mechanism of artificial selection and further dig out the causal genes
      related to important traits. In this study, three between-population and two
      within-population approaches, the Cross Population Extend Haplotype Homozygosity
      Test (XPEHH), the Cross Population Composite Likelihood Ratio (XPCLR), the F
      statistics (Fst), the Integrated Haplotype Score (iHS) and the Tajima's D, were
      implemented to detect the selection footprints on the X chromosome in three pig
      breeds using Illumina Porcine60K SNP chip. In the detection of selection
      footprints using between-population methods, 11, 11 and 7 potential selection
      regions with length of 15.62 Mb, 12.32 Mb and 9.38 Mb were identified in
      Landrace, Chinese Songliao and Yorkshire by XPEHH, respectively, and 16, 13 and
      17 potential selection regions with length of 15.20 Mb, 13.00 Mb and 19.21 Mb by
      XPCLR, 4, 2 and 4 potential selection regions with length of 3.20 Mb, 1.60 Mb and
      3.20 Mb by Fst. For within-population methods, 7, 10 and 9 potential selection
      regions with length of 8.12 Mb, 8.40 Mb and 9.99 Mb were identified in Landrace,
      Chinese Songliao and Yorkshire by iHS, and 4, 3 and 2 potential selection regions
      with length of 3.20 Mb, 2.40 Mb and 1.60 Mb by Tajima's D. Moreover, the
      selection regions from different methods were partly overlapped, especially the
      regions around 22~25 Mb were detected under selection in Landrace and Yorkshire
      while no selection in Chinese Songliao by all three between-population methods.
      Only quite few overlap of selection regions identified by between-population and
      within-population methods were found. Bioinformatics analysis showed that the
      genes relevant with meat quality, reproduction and immune were found in potential
      selection regions. In addition, three out of five significant SNPs associated
      with hematological traits reported in our genome-wide association study were
      harbored in potential selection regions.

PMID- 24740294
TI  - Relationship between p53 status and response to chemotherapy in patients with
      gastric cancer: a meta-analysis.
AB  - BACKGROUND: Previous studies have yielded conflicting results regarding the
      relationship between p53 status and response to chemotherapy in patients with
      gastric cancer. We therefore performed a meta-analysis to expound the
      relationship between p53 status and response to chemotherapy. METHODS/FINDINGS:
      Thirteen previously published eligible studies, including 564 cases, were
      identified and included in this meta-analysis. p53 positive status (high
      expression of p53 protein and/or a mutant p53 gene) was associated with improved
      response in gastric cancer patients who received chemotherapy (good response:
      risk ratio [RR] = 0.704; 95% confidence intervals [CI] = 0.550-0.903; P = 0.006).
      In further stratified analyses, association with a good response remained in the
      East Asian population (RR = 0.657; 95% CI = 0.488-0.884; P = 0.005), while in the
      European subgroup, patients with p53 positive status tended to have a good
      response to chemotherapy, although this did not reach statistical significance
      (RR = 0.828, 95% CI = 0.525-1.305; P = 0.417). As five studies used neoadjuvant
      chemotherapy (NCT) and one used neoadjuvant chemoradiotherapy (NCRT), we also
      analyzed these data, and found that p53 positive status was associated with a
      good response in gastric cancer patients who received chemotherapy-based
      neoadjuvant treatment (RR = 0.675, 95% CI = 0.463-0.985; P = 0.042). CONCLUSION:
      This meta-analysis indicated that p53 status may be a useful predictive biomarker
      for response to chemotherapy in gastric cancer. Further prospective studies with
      larger sample sizes and better study designs are required to confirm our
      findings.

PMID- 24740295
TI  - Acute moderate exercise does not further alter the autonomic nervous system
      activity in patients with sickle cell anemia.
AB  - A decreased global autonomic nervous system (ANS) activity and increased
      sympathetic activation in patients with sickle cell anemia (SCA) seem to worsen
      the clinical severity and could play a role in the pathophysiology of the
      disease, notably by triggering vaso-occlusive crises. Because exercise challenges
      the ANS activity in the general population, we sought to determine whether a
      short (<15 min) and progressive moderate exercise session conducted until the
      first ventilatory threshold had an effect on the ANS activity of a group of SCA
      patients and a group of healthy individuals (CONT group). Temporal and spectral
      analyses of the nocturnal heart rate variability were performed before and on the
      3 nights following the exercise session. Standard deviation of all normal RR
      intervals (SDNN), total power, low frequencies (LF) and high frequencies powers
      (HF) were lower but LF/HF was higher in SCA patients than in the CONT group.
      Moderate exercise did not modify ANS activity in both groups. In addition, no
      adverse clinical events occurred during the entire protocol. These results imply
      that this kind of short and moderate exercise is not detrimental for SCA
      patients. 

PMID- 24740296
TI  - Training and maintenance of a picture-based communication response in older
      adults with dementia.
AB  - We examined whether adults with dementia could learn to emit a picture-based
      communication response and if this skill would maintain over time. Three women
      with moderate to severe dementia were taught to exchange a picture card for a
      highly preferred activity. All participants quickly learned to exchange the
      picture card and maintained this response without practice. 

PMID- 24740297
TI  - The bacterial communities associated with honey bee (Apis mellifera) foragers.
AB  - The honey bee is a key pollinator species in decline worldwide. As part of a
      commercial operation, bee colonies are exposed to a variety of agricultural
      ecosystems throughout the year and a multitude of environmental variables that
      may affect the microbial balance of individuals and the hive. While many recent
      studies support the idea of a core microbiota in guts of younger in-hive bees, it
      is unknown whether this core is present in forager bees or the pollen they carry
      back to the hive. Additionally, several studies hypothesize that the foregut
      (crop), a key interface between the pollination environment and hive food stores,
      contains a set of 13 lactic acid bacteria (LAB) that inoculate collected pollen
      and act in synergy to preserve pollen stores. Here, we used a combination of 454
      based 16S rRNA gene sequencing of the microbial communities of forager guts,
      crops, and corbicular pollen and crop plate counts to show that (1) despite a
      very different diet, forager guts contain a core microbiota similar to that found
      in younger bees, (2) corbicular pollen contains a diverse community dominated by
      hive-specific, environmental or phyllosphere bacteria that are not prevalent in
      the gut or crop, and (3) the 13 LAB found in culture-based studies are not
      specific to the crop but are a small subset of midgut or hindgut specific
      bacteria identified in many recent 454 amplicon-based studies. The crop is
      dominated by Lactobacillus kunkeei, and Alpha 2.2 (Acetobacteraceae), highly
      osmotolerant and acid resistant bacteria found in stored pollen and honey. Crop
      taxa at low abundance include core hindgut bacteria in transit to their primary
      niche, and potential pathogens or food spoilage organisms seemingly vectored from
      the pollination environment. We conclude that the crop microbial environment is
      influenced by worker task, and may function in both decontamination and
      inoculation. 

PMID- 24740298
TI  - Human fibroblast reprogramming to pluripotent stem cells regulated by the
      miR19a/b-PTEN axis.
AB  - Induction of pluripotent stem cells (iPSC) by defined transcription factors is
      the recognized canonical means for somatic reprogramming, however, it remains
      incompletely understood how individual transcription factors affect cell fate
      decisions during the reprogramming process. Here, we report induction of
      fibroblast reprogramming by various transcriptional factors is mediated by a
      miR19a/b-PTEN axis. cMyc, one of the four Yamanaka factors known to stimulate
      both somatic cell reprogramming and tumorigenesis, induced the expression of
      multiple mircoRNAs, miR-17 ~ 92 cluster in particular, in the early stage of
      reprogramming of human fibroblasts. Importantly, miR-17 ~ 92 cluster could
      greatly enhance human fibroblast reprogramming induced by either the four
      Yamanaka factors (Oct4, Sox2, Klf4, and cMyc, or 4F) or the first three
      transcriptional factors (Oct4, Sox2, and Klf4, or 3F). Among members of this
      microRNA cluster, miR-19a/b exhibited the most potent effect on stimulating
      fibroblst reprogramming to iPSCs. Additional studies revealed that miR-19a/b
      enhanced iPSC induction efficiency by targeted inhibition of phosphatase and
      tensin homolog (PTEN), a renowned tumor suppressor whose loss-of-function
      mutations were found in multiple human malignancies. Our results thus demonstrate
      an important role of miR-19a/b-PTEN axis in the reprogramming of human
      fibroblasts, illustrating that the somatic reprogramming process and its
      underlying regulation pathways are intertwined with oncogenic signaling in human
      malignancies.

PMID- 24740299
TI  - The last frontier: catch records of white sharks (Carcharodon carcharias) in the
      Northwest Pacific Ocean.
AB  - White sharks are highly migratory apex predators, globally distributed in
      temperate, sub-tropical, and tropical waters. Knowledge of white shark biology
      and ecology has increased recently based on research at known aggregation sites
      in the Indian, Atlantic, and Northeast Pacific Oceans; however, few data are
      available for the Northwest Pacific Ocean. This study provides a meta-analysis of
      240 observations of white sharks from the Northwest Pacific Ocean between 1951
      and 2012. Records comprise reports of bycatch in commercial fisheries, media
      accounts, personal communications, and documentation of shark-human interactions
      from Russia (n = 8), Republic of Korea (22), Japan (129), China (32), Taiwan
      (45), Philippines (1) and Vietnam (3). Observations occurred in all months,
      excluding October-January in the north (Russia and Republic of Korea) and July
      August in the south (China, Taiwan, Philippines, and Vietnam). Population trend
      analysis indicated that the relative abundance of white sharks in the region has
      remained relatively stable, but parameterization of a 75% increase in observer
      effort found evidence of a minor decline since 2002. Reliably measured sharks
      ranged from 126-602 cm total length (TL) and 16-2530 kg total weight. The largest
      shark in this study (602 cm TL) represents the largest measured shark on record
      worldwide. For all countries combined the sex ratio was non-significantly biased
      towards females (1?1.1; n = 113). Of 60 females examined, 11 were confirmed
      pregnant ranging from the beginning stages of pregnancy (egg cases) to near term
      (140 cm TL embryos). On average, 6.0+/-2.2 embryos were found per litter (maximum
      of 10) and gestation period was estimated to be 20 months. These observations
      confirm that white sharks are present in the Northwest Pacific Ocean year-round.
      While acknowledging the difficulties of studying little known populations of a
      naturally low abundance species, these results highlight the need for dedicated
      research to inform regional conservation and management planning. 

PMID- 24740300
TI  - Vibronic models for nonlinear spectroscopy simulations.
AB  - It is already well established that the high-frequency intramolecular vibrations
      are responsible for many observed dynamic phenomena in linear and nonlinear
      electronic spectroscopy such as the spectral lineshape formation, the transition
      dipole moment, the lifetime borrowing, and vibrational and mixed coherence beats.
      All these implications together with the vibronic enhancement of the energy and
      charge transfer can be explained by the vibronic molecular exciton theory and are
      highly relevant for the description of the spectral dynamics in photosynthetic
      pigment-protein complexes. In this paper, a few critical points of the vibronic
      theory application to linear and nonlinear signals are discussed. Models, which
      differ in the selection and truncation of molecular basis, are compared by
      analyzing the energy spectrum and exciton-vibrational dynamics in the presence of
      the energetic disorder. The limits of the widely used one-particle approximation
      are defined. 

PMID- 24740302
TI  - Class 1 integrons and antibiotic resistance of clinical Acinetobacter
      calcoaceticus-baumannii complex in Poznan, Poland.
AB  - Sixty-three clinical isolates of Acinetobacter calcoaceticus-baumannii complex
      were analyzed for the presence of integrons and antimicrobial resistance. Class 1
      integrons were detected in 40 (63.5 %) isolates. None of them had class 2 or
      class 3 integrons. The majority of the integrons contained aacC1-orfA-orfB-aadA1
      gene cassette array. The presence of integrons was associated with the increased
      frequency of resistance to 12 of 15 antimicrobials tested, multi-drug resistance
      phenotype, and the overall resistance ranges of the strains.

PMID- 24740301
TI  - Interleukin-7 and Toll-like receptor 7 induce synergistic B cell and T cell
      activation.
AB  - OBJECTIVES: To investigate the potential synergy of IL-7-driven T cell-dependent
      and TLR7-mediated B cell activation and to assess the additive effects of
      monocyte/macrophages in this respect. METHODS: Isolated CD19 B cells and CD4 T
      cells from healthy donors were co-cultured with TLR7 agonist (TLR7A,
      Gardiquimod), IL-7, or their combination with or without CD14
      monocytes/macrophages (T/B/mono; 1 : 1 : 0,1). Proliferation was measured using
      3H-thymidine incorporation and Ki67 expression. Activation marker (CD19, HLA-DR,
      CD25) expression was measured by FACS analysis. Immunoglobulins were measured by
      ELISA and release of cytokines was measured by Luminex assay. RESULTS: TLR7
      induced B cell activation was not associated with T cell activation. IL-7-induced
      T cell activation alone and together with TLR7A synergistically increased numbers
      of both proliferating (Ki67+) B cells and T cells, which was further increased in
      the presence of monocytes/macrophages. This was associated by up regulation of
      activation markers on B cells and T cells. Additive or synergistic induction of
      production of immunoglobulins by TLR7 and IL-7 was associated by synergistic
      induction of T cell cytokines (IFNgamma, IL-17A, IL-22), which was only evident
      in the presence of monocytes/macrophages. CONCLUSIONS: IL-7-induced CD4 T cell
      activation and TLR7-induced B cell activation synergistically induce T helper
      cell cytokine and B cell immunoglobulin production, which is critically dependent
      on monocytes/macrophages. Our results indicate that previously described
      increased expression of IL-7 and TLR7 together with increased numbers of
      macrophages at sites of inflammation in autoimmune diseases like RA and pSS
      significantly contributes to enhanced lymphocyte activation.

PMID- 24740303
TI  - Multiple coupling of silanes with imido complexes of Mo.
AB  - The bis(imido) complexes ((t)BuN[double bond, length as m-dash])2Mo(PMe3)(L) (L =
      PMe3, C2H4) react with up to three equivalents of silane PhSiH3 to give the imido
      bridged disilyl silyl Mo(vi) complex ((t)BuN){MU
      (t)BuN(SiHPh)2}Mo(H)(SiH2Ph)(PMe3)2 (3) studied by NMR, IR and X-ray diffraction.
      NMR data supported by DFT calculations show that complex 3 is an unusual example
      of a silyl hydride of Mo(VI), without significant SiH interaction. Mechanistic
      NMR studies revealed that silane addition proceeds in a stepwise manner via a
      series of Si-H???M agostic and silanimine complexes whose structures were further
      elucidated by DFT calculations.

PMID- 24740304
TI  - Hospitalization records as a tool for evaluating performance of food- and water
      borne disease surveillance systems: a Massachusetts case study.
AB  - We outline a framework for evaluating food- and water-borne surveillance systems
      using hospitalization records, and demonstrate the approach using data on
      salmonellosis, campylobacteriosis and giardiasis in persons aged >=65 years in
      Massachusetts. For each infection, and for each reporting jurisdiction, we
      generated smoothed standardized morbidity ratios (SMR) and surveillance to
      hospitalization ratios (SHR) by comparing observed surveillance counts with
      expected values or the number of hospitalized cases, respectively. We examined
      the spatial distribution of SHR and related this to the mean for the entire
      state. Through this approach municipalities that deviated from the typical
      experience were identified and suspected of under-reporting. Regression analysis
      revealed that SHR was a significant predictor of SMR, after adjusting for
      population age-structure. This confirms that the spatial "signal" depicted by
      surveillance is in part influenced by inconsistent testing and reporting
      practices since municipalities that reported fewer cases relative to the number
      of hospitalizations had a lower relative risk (as estimated by SMR). Periodic
      assessment of SHR has potential in assessing the performance of surveillance
      systems. 

PMID- 24740306
TI  - A multicomponent approach to the synthesis of N-sulfonyl beta(2,3)-amino esters.
AB  - The multicomponent synthesis of alpha,beta-disubstituted N-sulfonyl beta-amino
      esters is described. It involves a zinc-mediated, cobalt-catalyzed three
      component reaction between sulfonylimines, acrylates and organic bromides. A
      possible mechanism is proposed, emphasizing the intermediate formation of an
      organocobalt as the initiator of a Mannich-like process. 

PMID- 24740307
TI  - Blood clot formation does not affect metastasis formation or tumor growth in a
      murine model of breast cancer.
AB  - Cancer is associated with increased fracture risk, due either to metastasis or
      associated osteoporosis. After a fracture, blood clots form. Because proteins of
      the coagulation cascade and activated platelets promote cancer development, a
      fracture in patients with cancer often raises the question whether it is a
      pathologic fracture or whether the fracture itself might promote the formation of
      metastatic lesions. We therefore examined whether blood clot formation results in
      increased metastasis in a murine model of experimental breast cancer metastasis.
      For this purpose, a clot was surgically induced in the bone marrow of the left
      tibia of immundeficient mice. Either one minute prior to or five minutes after
      clot induction, human cancer cells were introduced in the circulation by
      intracardiac injection. The number of cancer cells that homed to the intervention
      site was determined by quantitative real-time PCR and flow cytometry. Metastasis
      formation and longitudinal growth were evaluated by bioluminescence imaging. The
      number of cancer cells that homed to the intervention site after 24 hours was
      similar to the number of cells in the opposite tibia that did not undergo clot
      induction. This effect was confirmed using two more cancer cell lines.
      Furthermore, no difference in the number of macroscopic lesions or their growth
      could be detected. In the control group 72% developed a lesion in the left tibia.
      In the experimental groups with clot formation 79% and 65% developed lesions in
      the left tibia (p = ns when comparing each experimental group with the controls).
      Survival was similar too. In summary, the growth factors accumulating in a
      clot/hematoma are neither enough to promote cancer cell homing nor support growth
      in an experimental model of breast cancer bone metastasis. This suggests that
      blood clot formation, as occurs in traumatic fractures, surgical interventions,
      and bruises, does not increase the risk of metastasis formation. 

PMID- 24740308
TI  - Gene targeting of mouse Tardbp negatively affects Masp2 expression.
AB  - Amyotrophic Lateral Sclerosis (ALS) is a devastating adult onset
      neurodegenerative disease affecting both upper and lower motor neurons. TDP-43,
      encoded by the TARDBP gene, was identified as a component of motor neuron
      cytoplasmic inclusions in both familial and sporadic ALS and has become a
      pathological signature of the disease. TDP-43 is a nuclear protein involved in
      RNA metabolism, however in ALS, TDP-43 is mislocalized to the cytoplasm of
      affected motor neurons, suggesting that disease might be caused by TDP-43 loss of
      function. To investigate this hypothesis, we attempted to generate a mouse
      conditional knockout of the Tardbp gene using the classical Cre-loxP technology.
      Even though heterozygote mice for the targeted allele were successfully
      generated, we were unable to obtain homozygotes. Here we show that although the
      targeting vector was specifically designed to not overlap with Tardbp adjacent
      genes, the homologous recombination event affected the expression of a downstream
      gene, Masp2. This may explain the inability to obtain homozygote mice with
      targeted Tardbp. 

PMID- 24740309
TI  - Zeaxanthin dipalmitate therapeutically improves hepatic functions in an alcoholic
      fatty liver disease model through modulating MAPK pathway.
AB  - In the current study, the therapeutic effects of zeaxanthin dipalmitate (ZD) on a
      rat alcoholic fatty liver disease (AFLD) model were evaluated. After-treatment
      with ZD from the 5th week to the 10th week in a 10-week ethanol intragastric
      administration in rats significantly alleviated the typical AFLD symptoms,
      including reduction in rat body weight, accumulation of hepatic fat droplets,
      occurrence of oxidative stress, inflammation, chemoattractive responses and
      hepatic apoptosis in the liver. The reduction of liver function abnormalities by
      ZD was partly through lower expression level of cytochrome P450 2E1 (CYP2E1),
      diminished activity of nuclear factor kappa B (NF-kappaB) through the restoration
      of its inhibitor kappa B alpha (IkappaBalpha), and the modulation of MAPK
      pathways including p38 MAPK, JNK and ERK. ZD treatment alone did not pose obvious
      adverse effect on the healthy rat. In the cellular AFLD model, we also confirmed
      the inhibition of p38 MAPK and ERK abolished the beneficial effects of ZD. These
      results provide a scientific rationale for the use of zeaxanthin and its
      derivatives as new complementary agents for the prevention and treatment of
      alcoholic liver diseases. 

PMID- 24740310
TI  - Diffusion kurtosis imaging and high-resolution MRI demonstrate structural
      aberrations of caudate putamen and amygdala after chronic mild stress.
AB  - The pathophysiology of major depressive disorder (MDD) and other stress related
      disorders has been associated with aberrations in the hippocampus and the frontal
      brain areas. More recently, other brain regions, such as the caudate nucleus, the
      putamen and the amygdala have also been suggested to play a role in the
      development of mood disorders. By exposing rats to a variety of stressors over a
      period of eight weeks, different phenotypes, i.e. stress susceptible (anhedonic
      like) and stress resilient animals, can be discriminated based on the sucrose
      consumption test. The anhedonic-like animals are a well validated model for MDD.
      Previously, we reported that in vivo diffusion kurtosis imaging (DKI) of the
      hippocampus shows altered diffusion properties in chronically stressed rats
      independent of the hedonic state and that the shape of the right hippocampus is
      differing among the three groups, including unchallenged controls. In this study
      we evaluated diffusion properties in the prefrontal cortex, caudate putamen (CPu)
      and amygdala of anhedonic-like and resilient phenotypes and found that mean
      kurtosis in the CPu was significantly different between the anhedonic-like and
      resilient animals. In addition, axial diffusion and radial diffusion were
      increased in the stressed animal groups in the CPu and the amygdala,
      respectively. Furthermore, we found that the CPu/brain volume ratio was increased
      significantly in anhedonic-like animals as compared with control animals.
      Concurrently, our results indicate that the effects of chronic stress on the
      brain are not lateralized in these regions. These findings confirm the
      involvement of the CPu and the amygdala in stress related disorders and MDD.
      Additionally, we also show that DKI is a potentially important tool to promote
      the objective assessment of psychiatric disorders. 

PMID- 24740311
TI  - Unanticipated expanding neck mass under general anesthesia.

PMID- 24740312
TI  - An acceleromyographic train-of-four ratio of 1.0 reliably excludes respiratory
      muscle weakness after major abdominal surgery: a randomized double-blind study.
AB  - PURPOSE: This randomized double-blind study was designed to determine if
      respiratory muscle weakness - measured by maximum inspiratory pressure (MIP),
      maximum expiratory pressure (MEP), forced vital capacity (FVC), and forced
      expiratory volume in one second (FEV1) - persists even if an acceleromyographic
      train-of-four ratio (TOFR) of 1.0 is reached after major abdominal surgery.
      METHODS: Twenty patients underwent respiratory function tests before induction of
      anesthesia. Rocuronium was given, and the tests were repeated after extubation
      when the TOFR reached 1.0. The patients were then randomized to receive
      sugammadex 1 mg.kg(-1) or placebo, and the same tests were repeated five and 20
      min later. Between-group comparisons were carried out with a mixed-model analysis
      of variance analysis. RESULTS: After anesthesia and adequate epidural analgesia,
      MIP and MEP decreased by 60% in both groups. In the placebo group, MIP decreased
      from a pre-induction value (median [range]) of 61.8 [31.3-96.1] to 19.6 [8.3
      58.3] cm H2O after extubation without significant variation five and 20 min after
      placebo. In the sugammadex group, MIP decreased from a pre-induction value of
      57.8 [13.0-96.4] to 20.5 [6.4-67.3] cm H2O after extubation. No differences were
      recorded after sugammadex administration (P = 0.246 between groups). In the
      placebo group, MEP decreased from 88.8 [65.1-120.3] before induction to 37.6
      [13.4-70.6] cm H2O after extubation. In the sugammadex group, MEP decreased from
      85.5 [58.6-132.7] to 30.8 [10.5-60.5] cm H2O, with no improvement five and 20 min
      after either placebo or sugammadex administration (P = 0.648). Similarly, the FCV
      and FEV1 decreased 30-40% after extubation in both study groups. CONCLUSION:
      Acceleromyographic TOFR of 1.0 excludes residual neuromuscular paralysis.
      However, major respiratory dysfunction is observed after abdominal surgery. This
      trial was registered at ClinicalTrials.gov: NCT01503840.

PMID- 24740313
TI  - Common and Novel TMEM70 Mutations in a Cohort of Italian Patients with
      Mitochondrial Encephalocardiomyopathy.
AB  - ATP synthase or complex V (cV) of the oxidative phosphorylation system is
      responsible for the production of ATP, dissipating the electrochemical gradient
      generated by the mitochondrial respiratory chain. In addition to maternally
      transmitted cV dysfunction caused by mutations in mtDNA genes (MT-ATP6 or MT
      ATP8), encoding cV subunits, recessive mutations in the nuclear TMEM70 are the
      most frequent cause of ATP synthase deficiency.We report on a cohort of ten
      Italian patients presenting with neonatal lactic acidosis, respiratory distress,
      hypotonia, cardiomyopathy and psychomotor delay and harbouring mutations in
      TMEM70, including the common splice mutation and four novel variants. TMEM70
      protein was virtually absent in all tested TMEM70 patients' specimens.The exact
      function of TMEM70 is not known, but it is considered to impact on cV assembly
      since TMEM70 mutations have been associated with isolated cV activity reduction.
      We detected a clear cV biochemical defect in TMEM70 patients' fibroblasts,
      whereas the assay was not reliable in frozen muscle. Nevertheless, the evaluation
      of the amount of holocomplexes in patients with TMEM70 mutations showed a nearly
      absent cV in muscles and a strong decrease of cV with accumulation of sub
      assembly species in fibroblasts. In our cohort we found not only cV deficiencies
      but also impairment of other OXPHOS complexes. By ultrastructural analysis of
      muscle tissue from one patient with isolated cV deficiency, we found a severely
      impaired mitochondrial morphology with loss of the cristae. These findings
      indicate that cV impairment could indirectly alter other respiratory chain
      complex activities by disrupting the mitochondrial cristae structure. 

PMID- 24740314
TI  - Tracking natal dispersal in a coastal population of a migratory songbird using
      feather stable isotope (delta2H, delta34S) tracers.
AB  - Adult birds tend to show high fidelity to their breeding territory or disperse
      over relatively short distances. Gene flow among avian populations is thus
      expected to occur primarily through natal dispersal. Although natal dispersal is
      a critical demographic process reflecting the area over which population dynamics
      take place, low recapture rates of birds breeding for the first time have limited
      our ability to reliably estimate dispersal rates and distances. Stable isotope
      approaches can elucidate origins of unmarked birds and so we generated year- and
      age-specific delta2H and delta34S feather isoscapes (ca. 180 000 km2) of coastal
      breeding Ovenbirds (Seiurus aurocapilla) and used bivariate probability density
      functions to assign the likely natal areas of 35 males recruited as first-year
      breeders into a population located in northwestern New Brunswick, Canada. Most
      individuals (80-94% depending on the magnitude of an age correction factor used;
      i.e. 28-33 out of 35) were classified as residents (i.e. fledged within our study
      area) and estimated minimum dispersal distances of immigrants were between 40 and
      240 km. Even when considering maximum dispersal distances, the likely origin of
      most first-year breeders was<200 km from our study area. Our method identified
      recruitment into our population from large geographic areas with relatively few
      samples whereas previous mark-recapture based methods have required orders of
      magnitude more individuals to describe dispersal at such geographic scales. Natal
      dispersal movements revealed here suggest the spatial scale over which many
      population processes are taking place and we suggest that conservation plans
      aiming to maintain populations of Ovenbirds and ecologically-similar species
      should consider management units within 100 or at most 200 km of target breeding
      populations. 

PMID- 24740315
TI  - Planar-defect-rich zinc oxide nanoparticles assembled on carbon nanotube films as
      ultraviolet emitters and photocatalysts.
AB  - Structural defects in zinc oxide (ZnO) nanoparticles are complex and hard to be
      controlled during the synthesis, however, diversifying the chemical and physical
      performances. Here we report a rapid and low-temperature deposition method to
      fabricate planar-defect-rich ZnO nanoparticles on freestanding and aligned carbon
      nanotube films, different from common treatments which remove structural defects
      as many as possible. The defect energy states are very close to the valence band
      of ZnO and serve as recombination centers for a nearly monochromatic ultraviolet
      luminescence within a wavelength range of 373-376 nm. The absence of point
      defects, especially of oxygen vacancies whose energy level is <1 eV below the
      conduction band, allows photoinduced electrons and holes to take parts in
      possible photocatalytic reactions rather than to recombine at the shallow energy
      levels of planar defects.

PMID- 24740316
TI  - Art and science in the Renaissance: the case of Walther Hermann Ryff.

PMID- 24740317
TI  - Defending waste, fraud, and abuse.

PMID- 24740318
TI  - Does operative time affect infection rate in primary total knee arthroplasty?
AB  - BACKGROUND: Prolonged operative time may increase the risk of infection after
      total knee arthroplasty (TKA). Both surgeon-related and patient-related factors
      can contribute to increased operative times. QUESTIONS/PURPOSES: The purpose of
      this study was to determine (1) whether increased operative time is an
      independent risk factor for revision resulting from infection after TKA; (2)
      whether increasing body mass index (BMI) increased operative time; and (3)
      whether increasing experience substantially decreased operative time. METHODS: We
      retrospectively evaluated primary TKAs from our joint registry between March 2000
      and August 2012. Cox proportional hazard models were used to assess the
      relationship between operative time and revision resulting from infection after
      accounting for age, sex, BMI, and Agency for Healthcare Research and Quality
      comorbidity score. Of 9973 instances of primary TKA, 73 underwent revision
      surgery for infection (0.73%). RESULTS: After accounting for the confounders of
      age and sex, operative time was not found to have a significant effect; a 15
      minute increase in operative time increased the hazard of revision resulting from
      infection by only 15.6% (p=0.053; 95% confidence interval, 0.0%-34.0%). In
      addition, a five-unit increase in BMI was found to increase mean operative time
      by 1.9 minutes, on average, regardless of sex (p<0.0001). Operative time
      decreases with increasing experience but appears to plateau at approximately 300
      surgeries. CONCLUSIONS: Operative time is only one of many factors that may
      increase infection risk and may be influenced by numerous confounders. Increasing
      BMI increased operative time but the effect was modest. The effect of increasing
      experience on operative duration of this common procedure was surprisingly
      limited among our surgeons. LEVEL OF EVIDENCE: Level III, therapeutic study. See
      Guidelines for Authors for a complete description of levels of evidence.

PMID- 24740319
TI  - Polycyclic aromatic hydrocarbons in surface sediment of typical estuaries and the
      spatial distribution in Haihe river basin.
AB  - Polycyclic aromatic hydrocarbons (PAHs) with carcinogenic and mutagenic
      characteristics have been detected in many estuaries and bays around the world.
      To detect the contaminated level in typical estuaries in Haihe river basin,
      China, a comprehensive survey of 16 PAHs in surface sediment has been conducted
      and an ecological risk assessment has been taken. It showed that Haihe river
      estuary had the highest concentration, ranging from 92.91 to 15886.00 ng g(-1).
      And Luan river estuary has the lowest polluted level, ranging from 39.55 to
      328.10 ng g(-1). PAHs in sediment were dominated by low and mid molecular weight
      PAHs in all the sampling sites. Most of the sampling sites in all sampling
      seasons indicated a rarely happened ecological risk of SigmaPAHs, while the S6 in
      Haihe river estuary was in an occasionally anticipated risk. To illustrate the
      spatial distribution pattern of PAHs in surface sediment in Haihe river basin,
      the results were compared with previous research of the research team. Based on
      data of the comparison, it had been revealed that Haihe river had the most
      serious PAHs pollution, with an average concentration of 5884.86 ng g(-1), and
      showed the highest contamination level in all four ecological units. The
      SigmaPAHs concentration showed in a rank of reservoir > estuary > rural area >
      city.

PMID- 24740320
TI  - Rhizobium tibeticum activated with a mixture of flavonoids alleviates nickel
      toxicity in symbiosis with fenugreek (Trigonella foenum graecum L.).
AB  - The objective of this study is to explore the response of an activated Rhizobium
      tibeticum inoculum with a mixture of hesperetin (H) and apigenin (A) to improve
      the growth, nodulation, and nitrogen fixation of fenugreek (Trigonella foenum
      graecum L.) grown under nickel (Ni) stress. Three different sets of fenugreek
      seed treatments were conducted, in order to investigate the activated R.
      tibeticum pre-incubation effects on nodulation, nitrogen fixation and growth of
      fenugreek under Ni stress. Group (I): uninoculated seeds with R. tibeticum, group
      (II): inoculated seeds with uninduced R. tibeticum group (III): inoculated seeds
      with induced R. tibeticum. The present study revealed that Ni induced deleterious
      effects on rhizobial growth, nod gene expression, nodulation, phenylalanine
      ammonia-lyase (PAL) and glutamine synthetase activities, total flavonoids content
      and nitrogen fixation, while the inoculation with an activated R. tibeticum
      significantly improved these values compared with plants inoculated with
      uninduced R. tibeticum. PAL activity of roots plants inoculated with induced R.
      tibeticum and grown hydroponically at 75 and 100 mg L(-1) Ni and was
      significantly increased compared with plants receiving uninduced R. tibeticum.
      The total number and fresh mass of nodules, nitrogenase activity of plants
      inoculated with induced cells grown in soil treated up to 200 mg kg(-1) Ni were
      significantly increased compared with plants inoculated with uninduced cells.
      Plants inoculated with induced R. tibeticum dispalyed a significant increase in
      the dry mass compared with those treated with uninduced R. tibeticum. Activation
      of R. tibeticum inoculum with a mixture of hesperetin and apigenin has been
      proven to be practically important in enhancing nodule formation, nitrogen
      fixation and growth of fenugreek grown in Ni contaminated soils.

PMID- 24740321
TI  - High fat, low carbohydrate diet limit fear and aggression in Gottingen minipigs.
AB  - High fat, low carbohydrate diets have become popular, as short-term studies show
      that such diets are effective for reducing body weight, and lowering the risk of
      diabetes and cardiovascular disease. There is growing evidence from both humans
      and other animals that diet affects behaviour and intake of fat has been linked,
      positively and negatively, with traits such as exploration, social interaction,
      anxiety and fear. Animal models with high translational value can help provide
      relevant and important information in elucidating potential effects of high fat,
      low carbohydrate diets on human behaviour. Twenty four young, male Gottingen
      minipigs were fed either a high fat/cholesterol, low carbohydrate diet or a low
      fat, high carbohydrate/sucrose diet in contrast to a standard low fat, high
      carbohydrate minipig diet. Spontaneous behaviour was observed through video
      recordings of home pens and test-related behaviours were recorded during tests
      involving animal-human contact and reaction towards a novel object. We showed
      that the minipigs fed a high fat/cholesterol, low carbohydrate diet were less
      aggressive, showed more non-agonistic social contact and had fewer and less
      severe skin lesions and were less fearful of a novel object than minipigs fed low
      fat, high carbohydrate diets. These results found in a porcine model could have
      important implications for general health and wellbeing of humans and show the
      potential for using dietary manipulations to reduce aggression in human society. 

PMID- 24740323
TI  - Multi-platform compatible software for analysis of polymer bending mechanics.
AB  - Cytoskeletal polymers play a fundamental role in the responses of cells to both
      external and internal stresses. Quantitative knowledge of the mechanical
      properties of those polymers is essential for developing predictive models of
      cell mechanics and mechano-sensing. Linear cytoskeletal polymers, such as actin
      filaments and microtubules, can grow to cellular length scales at which they
      behave as semiflexible polymers that undergo thermally-driven shape deformations.
      Bending deformations are often modeled using the wormlike chain model. A
      quantitative metric of a polymer's resistance to bending is the persistence
      length, the fundamental parameter of that model. A polymer's bending persistence
      length is extracted from its shape as visualized using various imaging
      techniques. However, the analysis methodologies required for determining the
      persistence length are often not readily within reach of most biological
      researchers or educators. Motivated by that limitation, we developed user
      friendly, multi-platform compatible software to determine the bending persistence
      length from images of surface-adsorbed or freely fluctuating polymers. Three
      different types of analysis are available (cosine correlation, end-to-end and
      bending-mode analyses), allowing for rigorous cross-checking of analysis results.
      The software is freely available and we provide sample data of adsorbed and
      fluctuating filaments and expected analysis results for educational and tutorial
      purposes. 

PMID- 24740322
TI  - Niclosamide inhibits androgen receptor variants expression and overcomes
      enzalutamide resistance in castration-resistant prostate cancer.
AB  - PURPOSE: Enzalutamide, a second-generation antiandrogen, was recently approved
      for the treatment of castration-resistant prostate cancer (CRPC) in patients who
      no longer respond to docetaxel. Despite these advances that provide temporary
      respite, resistance to enzalutamide occurs frequently. Androgen receptor (AR)
      splice variants such as AR-V7 have recently been shown to drive castration
      resistant growth and resistance to enzalutamide. This study was designed to
      identify inhibitors of AR variants and test its ability to overcome resistance to
      enzalutamide. EXPERIMENTAL DESIGN: The drug screening was conducted using
      luciferase activity assay to determine the activity of AR-V7 after treatment with
      the compounds in the Prestwick Chemical Library, which contains about 1,120 FDA
      approved drugs. The effects of the identified inhibitors on AR-V7 activity and
      enzalutamide sensitivity were characterized in CRPC and enzalutamide-resistant
      prostate cancer cells in vitro and in vivo. RESULTS: Niclosamide, an FDA-approved
      antihelminthic drug, was identified as a potent AR-V7 inhibitor in prostate
      cancer cells. Niclosamide significantly downregulated AR-V7 protein expression by
      protein degradation through a proteasome-dependent pathway. Niclosamide also
      inhibited AR-V7 transcription activity and reduced the recruitment of AR-V7 to
      the PSA promoter. Niclosamide inhibited prostate cancer cell growth in vitro and
      tumor growth in vivo. Furthermore, the combination of niclosamide and
      enzalutamide resulted in significant inhibition of enzalutamide-resistant tumor
      growth, suggesting that niclosamide enhances enzalutamide therapy and overcomes
      enzalutamide resistance in CRPC cells. CONCLUSIONS: Niclosamide was identified as
      a novel inhibitor of AR variants. Our findings offer preclinical validation of
      niclosamide as a promising inhibitor of AR variants to treat, either alone or in
      combination with current antiandrogen therapies, patients with advanced prostate
      cancer, especially those resistant to enzalutamide.

PMID- 24740324
TI  - Synthesis of N-alkyl isatins via oxidative cyclization of N-alkyl 2
      bromo(chloro)acetanilides.
AB  - A highly efficient method for the synthesis of N-alkyl isatins starting from N
      alkyl 2-bromo or 2-chloro acetanilides is described. The starting materials are
      easy to prepare and the yields of isatins are generally high. Operationally the
      reaction is very simple to run. Even though best results were obtained with a
      catalytic amount of CuI, the reactions of N-alkyl 2-bromo acetanilides actually
      performed well even in the absence of any metal catalyst. 

PMID- 24740325
TI  - Does abortion reduce self-esteem and life satisfaction?
AB  - PURPOSE: This study aims to assess the effects of obtaining an abortion versus
      being denied an abortion on self-esteem and life satisfaction. METHODS: We
      present the first 2.5 years of a 5-year longitudinal telephone-interview study
      that follows 956 women who sought an abortion from 30 facilities across the USA.
      We examine the self-esteem and life satisfaction trajectories of women who sought
      and received abortions just under the facility's gestational age limit, of women
      who sought and received abortions in their first trimester of pregnancy, and of
      women who sought abortions just beyond the facility gestational limit and were
      denied an abortion. We use adjusted mixed effects linear regression analyses to
      assess whether the trajectories of women who sought and obtained an abortion
      differ from those who were denied one. RESULTS: Women denied an abortion
      initially reported lower self-esteem and life satisfaction than women who sought
      and obtained an abortion. For all study groups, except those who obtained first
      trimester abortions, self-esteem and life satisfaction improved over time. The
      initially lower levels of self-esteem and life satisfaction among women denied an
      abortion improved more rapidly reaching similar levels as those obtaining
      abortions at 6 months to one year after abortion seeking. For women obtaining
      first trimester abortions, initially higher levels of life satisfaction remained
      steady over time. CONCLUSIONS: There is no evidence that abortion harms women's
      self-esteem or life satisfaction in the short term.

PMID- 24740326
TI  - Assessing individual and neighborhood social factors in child oral health-related
      quality of life: a multilevel analysis.
AB  - PURPOSE: It has been suggested that subjective measures of oral health are
      influenced by both individual and contextual characteristics. This study assessed
      the relationship between neighborhood and individual social networks and child
      oral health-related quality of life (COHRQoL). METHODS: This study followed a
      cross-sectional design using a multistage sample of 478 children aged 1-5 years
      old. Caregivers completed the Brazilian version of the Early Childhood Oral
      Health Impact Scale (ECOHIS) and answered questions related to socioeconomic
      status and social network. The dental examination provided information on the
      prevalence of dental caries, dental trauma, and occlusion. Contextual social
      determinants included the presence of cultural community centers and of workers'
      association in the neighborhood. Data analysis considered the total ECOHIS scores
      as the outcome and neighborhood/individual social networks as the independent
      variables. A multilevel Poisson regression model was used to investigate the
      association among individual and contextual characteristics and COHRQoL. RESULTS:
      Total ECOHIS scores ranged from 0 to 41 (possible range 0-52). The mean ECOHIS
      score was low (mean = 1.8, SD = 3.9), and the functional domain presented the
      highest mean impact on COHRQoL (mean = 0.5, SD = 1.4). Following adjusted
      analysis, low household income, visiting a neighbor less than once a month, the
      presence of anterior open bite, dental trauma, and dental caries were identified
      as individual determinants of negative impact on a child's quality of life. These
      variables remained associated with the outcome even after adding the contextual
      level variables in the model. At the contextual level, the presence of community
      cultural centers was associated with overall mean ECOHIS score; higher impacts on
      COHRQoL were observed in those living in neighborhoods without cultural community
      centers. CONCLUSION: There is a significant association between individual and
      contextual social determinants and COHRQoL; unfavorable social conditions and
      poor socioeconomic status have a negative impact on caregiver reports of
      children's oral health-related quality of life.

PMID- 24740329
TI  - Risk of melanoma in people with HIV/AIDS in the pre- and post-HAART eras: a
      systematic review and meta-analysis of cohort studies.
AB  - OBJECTIVE: Following the introduction of highly active antiretroviral therapy
      (HAART) the risk of AIDS-defining cancers decreased but incidence of many non
      AIDS-defining cancers has reportedly increased in those with HIV/AIDS. Whether
      melanoma risk has also changed in HIV/AIDS patients post-HAART is unknown and
      therefore we evaluated this in comparison with the risk before HAART. DESIGN:
      Systematic review and meta-analysis. METHODS: We searched Medline, Embase and ISI
      science citation index databases to April 2013. All cohort studies of patients
      diagnosed with HIV/AIDS that permitted quantitative assessment of the association
      with melanoma were eligible. Detailed quality assessment of eligible studies was
      conducted, focussing particularly on adjustment for ethnicity, a priori
      considered essential for an unbiased assessment of melanoma risk. Data were
      pooled using a random effects model. RESULTS: From 288 articles, we identified 21
      that met the inclusion criteria, 13 presenting data for the post-HAART era and 8
      for the pre-HAART era. Post-HAART the pooled relative risk (pRR) for the
      association between HIV/AIDS and melanoma was 1.26 (95% CI, 0.97-1.64) and 1.50
      (95% CI 1.12-2.01) among studies that accounted for ethnicity, with evidence of
      significant heterogeneity (P = 0.004, I2 = 55.5). Pre-HAART pRRs were 1.26 (95%
      CI 1.11-1.43; P het = 0.82) and 1.28 (95% CI 1.10-1.49) among studies adjusted
      for ethnicity. CONCLUSIONS: People with HIV/AIDS remain at a significantly
      increased risk of developing melanoma in the post-HAART era. White skinned people
      with HIV/AIDS should be screened regularly and counselled against excessive sun
      exposure.

PMID- 24740327
TI  - Introduction of aromatic ring-containing substituents in cyclic nucleotides is
      associated with inhibition of toxin uptake by the hepatocyte transporters OATP
      1B1 and 1B3.
AB  - Analogs of the cyclic nucleotides cAMP and cGMP have been extensively used to
      mimic or modulate cellular events mediated by protein kinase A (PKA), Exchange
      protein directly activated by cAMP (Epac), or protein kinase G (PKG). We report
      here that some of the most commonly used cyclic nucleotide analogs inhibit
      transmembrane transport mediated by the liver specific organic anion transporter
      peptides OATP1B1 and OATP1B3, unrelated to actions on Epac, PKA or PKG. Several
      cAMP analogs, particularly with 8-pCPT-substitution, inhibited nodularin (Nod)
      induced primary rat hepatocyte apoptosis. Inhibition was not mediated by PKA or
      Epac, since increased endogenous cAMP, and some strong PKA- or Epac-activating
      analogs failed to protect cells against Nod induced apoptosis. The cAMP analogs
      inhibiting Nod induced hepatocyte apoptosis also reduced accumulation of
      radiolabeled Nod or cholic acid in primary rat hepatocytes. They also inhibited
      Nod induced apoptosis in HEK293 cells with enforced expression of OATP1B1 or 1B3,
      responsible for Nod transport into cells. Similar results were found with
      adenosine analogs, disconnecting the inhibitory effect of certain cAMP analogs
      from PKA or Epac. The most potent inhibitors were 8-pCPT-6-Phe-cAMP and 8-pCPT-2'
      O-Me-cAMP, whereas analogs like 6-MB-cAMP or 8-Br-cAMP did not inhibit Nod
      uptake. This suggests that the addition of aromatic ring-containing substituents
      like the chloro-phenyl-thio group to the purines of cyclic nucleotides increases
      their ability to inhibit the OATP-mediated transport. Taken together, our data
      show that aromatic ring substituents can add unwanted effects to cyclic
      nucleotides, and that such nucleotide analogs must be used with care,
      particularly when working with cells expressing OATP1B1/1B3, like hepatocytes, or
      intact animals where hepatic metabolism can be an issue, as well as certain
      cancer cells. On the other hand, cAMP analogs with substituents like bromo,
      monobutyryl were non-inhibitory, and could be considered an alternative when
      working with cells expressing OATP1 family members. 

PMID- 24740330
TI  - Analysis of ultra-deep pyrosequencing and cloning based sequencing of the basic
      core promoter/precore/core region of hepatitis B virus using newly developed
      bioinformatics tools.
AB  - AIMS: The aims of this study were to develop bioinformatics tools to explore
      ultra-deep pyrosequencing (UDPS) data, to test these tools, and to use them to
      determine the optimum error threshold, and to compare results from UDPS and
      cloning based sequencing (CBS). METHODS: Four serum samples, infected with either
      genotype D or E, from HBeAg-positive and HBeAg-negative patients were randomly
      selected. UDPS and CBS were used to sequence the basic core promoter/precore
      region of HBV. Two online bioinformatics tools, the "Deep Threshold Tool" and the
      "Rosetta Tool" (http://hvdr.bioinf.wits.ac.za/tools/), were built to test and
      analyze the generated data. RESULTS: A total of 10952 reads were generated by
      UDPS on the 454 GS Junior platform. In the four samples, substitutions, detected
      at 0.5% threshold or above, were identified at 39 unique positions, 25 of which
      were non-synonymous mutations. Sample #2 (HBeAg-negative, genotype D) had
      substitutions in 26 positions, followed by sample #1 (HBeAg-negative, genotype E)
      in 12 positions, sample #3 (HBeAg-positive, genotype D) in 7 positions and sample
      #4 (HBeAg-positive, genotype E) in only four positions. The ratio of nucleotide
      substitutions between isolates from HBeAg-negative and HBeAg-positive patients
      was 3.5 ? 1. Compared to genotype E isolates, genotype D isolates showed greater
      variation in the X, basic core promoter/precore and core regions. Only 18 of the
      39 positions identified by UDPS were detected by CBS, which detected 14 of the 25
      non-synonymous mutations detected by UDPS. CONCLUSION: UDPS data should be
      approached with caution. Appropriate curation of read data is required prior to
      analysis, in order to clean the data and eliminate artefacts. CBS detected fewer
      than 50% of the substitutions detected by UDPS. Furthermore it is important that
      the appropriate consensus (reference) sequence is used in order to identify
      variants correctly.

PMID- 24740331
TI  - The efficacy of a hemostatic agent in anticoagulant drug-induced rat bleeding
      model.
AB  - BACKGROUND: Bleeding is a major problem in warfarin pretreated patients who need
      emergency surgical procedures. APH is a hemostatic agent with ultra-hydrophilic
      and particulate properties. This study aimed to evaluate the in vivo hemostatic
      effect of APH in rats pretreated with warfarin. METHODS: Forty-eight Wistar rats
      were divided into two main groups: one group was pretreated with warfarin and the
      other group was not. These two groups were further divided into three subgroups
      according to the administration of APH, wheat meal, or saline, for a total of six
      subgroups. Standard full thickness tissue defects were performed on the backs of
      the rats. Saline, wheat meal, or APH were administered to the bleeding defect
      site in both main groups. Hemostasis time and amount of bleeding were calculated.
      RESULTS: The bleeding time in rats administered APH was significantly shorter
      than those administered wheat meal and saline. Consequently, the amount of
      bleeding was significantly less in the APH groups than in the control groups.
      CONCLUSION: APH has an effective hemostatic property in rats pretreated or non
      pretreated with anticoagulants. Hemostatic agents can be useful for incidences of
      external bleedings, which are increasing because of anticoagulation.

PMID- 24740332
TI  - Evaluation of the Alvarado score in acute abdominal pain.
AB  - BACKGROUND: The Alvarado score is utilized to determine the likelihood of
      appendicitis based on clinical signs, symptoms, and laboratory results. The goal
      of this study was to determine whether Alvarado scores can be used to aid in the
      accurate diagnosis of appendicitis. METHODS: Alvarado score evaluations were
      performed on 300 patients that were referred to or presented to the emergency
      room with acute abdominal pain. RESULTS: Out of the 300 patients, 85.66% had
      Alvarado scores of 7 or less and 14.33% had Alvarado scores greater than 7. For
      patients that had confirmed appendicitis, 25.7% had Alvarado scores of 7 or less,
      whereas 93% had Alvarado scores greater than 7. The Alvarado scoring system had
      poor sensitivity at 37%, and the specificity of this scoring system was high at
      95%. CONCLUSION: Our findings suggest that patients presenting with abdominal
      pain and Alvarado scores greater than 7 are more likely to have appendicitis. As
      such, the Alvarado scoring system may be utilized to better predict whether a
      patient has appendicitis. An Alvarado score that is positive for appendicitis
      would consist of a score greater than 7, which suggests that the patient has a
      93% chance of having appendicitis. A negative Alvarado score is 7 or lower,
      suggesting a 26% probability of having appendicitis. In all, the Alvarado scoring
      system is a good rule-in test, but it does not adequately rule-out appendicitis.

PMID- 24740333
TI  - Case series of non-operative management vs. operative management of splenic
      injury after blunt trauma.
AB  - BACKGROUND: The spleen is the most easily injured organ in abdominal trauma. The
      conservative, operative approach has been challenged by several reports of
      successful non-operative management aided by the power of modern diagnostic
      imaging. The aim of our retrospective study was to compare non-operative
      management with surgery for cases of splenic injury. METHODS: We compared seven
      patients who were treated with non-operative management (NOM) between 2007 and
      2011 to six patients with similar pre-operative characteristics who underwent
      operative management (OM). RESULTS: The average hospital stay was lower in the
      NOM group than in the OM group, although the difference was not statistically
      significant. The NOM group required significantly fewer transfusions, and no
      patients in the NOM group required admission to the intensive care unit. In
      contrast 83% of patients in the OM group were admitted to the intensive care
      unity. The failure rate of NOM was 14.3% in our experience. CONCLUSION: In our
      experience, NOM is the treatment of choice for grade I, II and III blunt splenic
      injuries. NOM is slightly less than surgery, but this is an unadjusted comparison
      and the 95% confidence interval is extremely wide - from 0.04 to 16.99.
      Splenectomy was the chosen technique in patients who met exclusion criteria for
      NOM, as well as for patients with grade IV and V injury.

PMID- 24740334
TI  - Non-operative management (NOM) of blunt hepatic trauma: 80 cases.
AB  - BACKGROUND: Liver is the most frequently injured organ upon abdominal trauma. We
      present a group of patients with blunt hepatic trauma who were managed without
      any invasive diagnostic tools and/or surgical intervention. METHODS: A total of
      80 patients with blunt liver injury who were hospitalized to the general surgery
      clinic or other clinics due to the concomitant injuries were followed non
      operatively. The normally distributed numeric variables were evaluated by
      Student's t-test or one way analysis of variance, while non-normally distributed
      variables were analyzed by Mann-Whitney U-test or Kruskal-Wallis variance
      analysis. Chi-square test was also employed for the comparison of categorical
      variables. Statistical significance was assumed for p<0.05. RESULTS: There was no
      significant relationship between patients' Hgb level and liver injury grade,
      outcome, and mechanism of injury. Also, there was no statistical relationship
      between liver injury grade, outcome, and mechanism of injury and ALT levels as
      well as AST level. There was no mortality in any of the patients. CONCLUSION:
      During the last quarter of century, changes in the diagnosis and treatment of
      liver injury were associated with increased survival. NOM of liver injury in
      patients with stable hemodynamics and hepatic trauma seems to be the gold
      standard.

PMID- 24740335
TI  - Comparison of diagnostic peritoneal lavage and focused assessment by sonography
      in trauma as an adjunct to primary survey in torso trauma: a prospective
      randomized clinical trial.
AB  - BACKGROUND: Lately, Focused Assessment with Sonography in Trauma (FAST) is
      preferred over diagnostic peritoneal lavage (DPL) as adjunct to primary survey.
      However, this is not evidence-based as there has been no randomized trial.
      METHODS: In this study, 200 consecutive torso trauma patients meeting inclusion
      criteria were randomized to undergo either DPL or FAST. The results were then
      compared with either contrast enhanced computerized tomography (CECT) (in
      patients managed non-operatively) or laparotomy findings (in patients undergoing
      operative treatment). Outcome parameters were: result of the test, therapeutic
      usefulness, role in diagnosing bowel injury and time taken to perform the
      procedure. RESULTS: Two hundred patients with a mean age of 28.3 years were
      studied, 98 in FAST and 102 in DPL group. 104 sustained blunt trauma and 76
      sustained penetrating trauma due to stabbing. In addition, 38 (38.7%) were FAST
      positive and 48 (47%) were DPL positive (p=0.237, not significant). As a guide to
      therapeutically beneficial laparotomy, negative DPL was better than negative
      FAST. For non-operative decisions, positive FAST was significantly better than
      positive DPL. DPL was significantly better than FAST in detecting as well as not
      missing the bowel injuries. DPL took significantly more time than FAST to
      perform. CONCLUSION: This study shows that DPL is better than FAST.

PMID- 24740336
TI  - Are neutrophil-lymphocyte ratio and platelet-lymphocyte ratio as effective as
      Fournier's gangrene severity index for predicting the number of debridements in
      Fourner's gangrene?
AB  - BACKGROUND: Fournier's gangrene (FG) is a rapidly progressive and necrotizing
      infection of the subcutaneous and fascial tissues with a high mortality rate. In
      the present study, we aimed to investigate prognostic factors and analyze the
      outcomes of 68 patients in a tertiary reference hospital. METHODS: Patients
      admitted to the emergency department were investigated retrospectively between
      January 2006 and January 2013 and divided into two groups. The patients in Group
      I (G1) required one debridement, and Group II (G2) patients required more than
      one. Patient demographic and clinical characteristics were encoded. Fournier's
      Gangrene Severity Index (FGSI) scores, neutrophil-lymphocyte ratios (NLR), and
      platelet-lymphocyte ratios (PLR) were calculated. Prognostic factors were
      compared between the groups. RESULTS: There were no statistically significant
      differences between the groups in terms of mean age, female-male ratio, or
      duration of symptoms on admission; however, there were more infection sources,
      predisposal factors, and positive culture results in G2. Additionally, hospital
      stay, total cost, and mortality rate values were high in G2. We found
      statistically higher NLR and PLR ratios in G2, but there was no significant
      difference in FGSI scores between the groups. CONCLUSION: The FGSI scoring system
      was not found to be valuable in determining prognosis. However, NLR and PLR were
      valuable, and previous use of NLR and PLR for determining Fournier's gangrene
      prognosis could not be found in the English literature.

PMID- 24740337
TI  - Abdominal solid organ injury in trauma patients with pelvic bone fractures.
AB  - BACKGROUND: We analyzed the clinical progression of trauma patients with pelvic
      bone fractures so to determine the risk factors associated with sustaining
      concurrent abdominal solid organ injuries. METHODS: This study was a
      retrospective chart review. Subjects were categorized based on injury type: solid
      organ versus non-solid organ injury groups. These study groups were compared
      based on demographics, treatments, and clinical outcomes. Potential risk factors
      that may contribute to the occurrence of abdominal solid organ injury in trauma
      patients with pelvic bone fractures were evaluated. RESULTS: The solid organ
      injury group included 17.4% of all the patients in the study (n=69). Fall from
      height occurred at greater distances in patients that sustained solid organ
      injuries as opposed to patients with non-solid organ injuries. Initial blood
      pressure and Revised Trauma Scores were lower in the solid organ injury group.
      Shock diagnosed immediately upon emergency department arrival was a risk factor
      for intra-abdominal solid organ injuries in trauma patients with pelvic bone
      fractures. Clinical prognosis for patients in the solid organ injury group was
      poorer and more invasive treatments were performed for patients in this group.
      CONCLUSION: Traumatic pelvic fracture patient prognosis needs to be improved
      through early diagnosis and prompt delivery of aggressive treatments based on
      rapid identification of abdominal solid organ injuries.

PMID- 24740338
TI  - [Investigation of the relationship between severity of injury, return to work,
      impairment, and activity participation in hand and forearm injuries].
AB  - BACKGROUND: Forearm and hand injuries are the main cause of work-related
      disability. This study was planned to investigate the relationship between
      severity of injury, time of return to work, impairment, and activity
      participation of patients with hand and forearm injuries. METHODS: One hundred
      and thirty patients who had patients who had had forearm or hand injuries with a
      mean age of 31+/-11.13 years participated in this study. Injury severity was
      evaluated using Modified Hand and Forearm Injury Severity Scoring (MHISS) after
      surgery. Patients were evaluated using the Jebsen Hand Function Test (JHFT) and
      Buck-Gramko scoring eight weeks after injury. Additionally, grip strength was
      evaluated with a dynamometer, and disability/symptom score was evaluated using
      the Turkish version of the Disabilities of the Arm, Shoulder, and Hand (DASH-T)
      questionnaire twelve weeks after injury. RESULTS: A significant relationship
      between MHISS, hand strength, time of return to work, DASH-T, and Buck-Gramko
      scores of patients with forearm and hand injuries was identified (p<=0.05).
      Higher impairment was significantly related to body structure and body functions
      (1.86+/-1.47), and the most limited activity was writing (2.06+/-1.50) regarding
      ICF framework. CONCLUSION: Higher MHISS scores were associated with delays in
      returning to work and lower activity participation. The DASH-T score was the most
      strongly associated with time of return to work. Furthermore, there is a positive
      relation between time of return to work and activity participation of patients.

PMID- 24740339
TI  - [An easy, safe and affective method for the treatment of intussusception:
      ultrasound-guided hydrostatic reduction].
AB  - BACKGROUND: Intussusception is one of the important causes of intestinal
      obstruction in children. Hydrostatic reduction under ultrasound guidance is a
      popular treatment method for intussusception. In the present study, we aimed to
      explain the demographic characteristics of and treatment approaches in patients
      diagnosed with intussusception by ultrasound. METHODS: Forty-one patients
      diagnosed with intussusception by ultrasound between August 2011 and May 2013
      were retrospectively analyzed. Twenty-four of these patients who had no
      contraindications had been treated with ultrasound-guided hydrostatic reduction.
      RESULTS: Twenty-four of the patients were male and 17 were female, a 1.4/1 male
      to-female ratio. The majority of the patients were between the ages of 6-24
      months and 2-5 years. The mean age was 31.12+/-26.32 months (range 3-125).
      Patients were more frequently diagnosed in April and May. Seventeen patients who
      had clinical contraindications enrolled directly for surgery. In 20 of the 24
      patients who underwent ultrasound-guided hydrostatic reduction, reduction was
      achieved. Three experienced recurrence. In two of these patients, successful
      reduction was achieved with the second attempt. The remaining patient was
      enrolled for surgery. Hydrostatic reduction was performed 26 times on these 24
      patients, and in 22, success was achieved (84.6%). No procedure-related
      complications occurred in the patients. CONCLUSION: Ultrasound-guided hydrostatic
      reduction, with its high success rates and lack of radiation risk, should be the
      first choice therapeutic approach for children diagnosed with intussusception.

PMID- 24740340
TI  - [Blunt renal trauma in children: a retrospective analysis of 41 cases].
AB  - BACKGROUND: The majority of renal injury secondary to blunt abdominal trauma can
      be successfully treated conservatively. In the present study, the clinical
      features and outcomes of children who presented with renal injury secondary to
      blunt abdominal trauma were evaluated. METHODS: This study was carried out
      retrospectively using data from children at the Department of Pediatric Surgery
      who were hospitalized for renal injury due to blunt abdominal trauma between 2000
      and 2012. Patient characteristics, clinical presentation, management strategy,
      and outcome were evaluated. RESULTS: Forty-one patients were hospitalized. The
      mean age of the patients was 10+/-4.85 years. The majority of renal injuries were
      grade 1 and 2. Falling was the cause of most renal injuries. All patients were
      initially treated conservatively. Three patients underwent acute surgical
      exploration for life-threatening renal bleeding (grade 4-5 injury). Nephrectomy
      was performed in 3 patients due to injury to the pedicle. CONCLUSION: The
      conservative treatment of pediatric renal parenchymal injuries is safe and
      effective in children. Although the vast majority of renal injuries do not
      require surgical intervention, life-threatening renal bleeding, regardless of the
      grade of injury, should be treated surgically.

PMID- 24740341
TI  - Acute liver failure secondary to hepatic compartment syndrome: case report and
      literature review.
AB  - We report a case of a patient with a delayed large intrahepatic hematoma and
      transient decline in hemoglobin to 62 g/L 18 days after liver injury. Abdominal
      computed tomography revealed seriously flattening of inferior vena cava, which
      was consistent with compression by the enlarging hematoma. Although traditionally
      there was no indication for surgical intervention, the patient developed acute
      liver failure with a progressive increase in liver enzymes and bilirubin. We
      postulated the ever-expanding hematoma might have led to dramatically elevated
      intrahepatic pressures that in turn restricted hepatic vein reflux and
      subsequently resulted in acute liver failure. Therefore, she underwent
      percutaneous drainage, and the decompression instantly reversed the liver injury.
      This phenomenon is similar to the well-described abdominal compartment syndrome,
      which is defined as new onset organ dysfunction or failure secondary to sustained
      intraabdominal hypertension and in which decompression is the standard treatment.

PMID- 24740342
TI  - Endoscopic endonasal removal of a sphenoidal sinus foreign body extending into
      the intracranial space.
AB  - Sphenoidal sinus foreign bodies are very rare entities that are often associated
      with a cranial and/or orbital trauma. In this paper, a case of a metallic foreign
      body that pierced the sphenoid sinus and penetrated into the intracranial space
      due to a work accident is presented. A 29-year-old male was referred to our
      clinic due to a right orbital penetrating trauma. Skull X-ray and computed
      tomography (CT) scans demonstrated a foreign body inside the sphenoidal sinus,
      extending to the left temporal fossa. The foreign body was removed using an
      endoscopic endonasal technique, and the skull base was reconstructed with a
      multilayer closure technique. There were no complications during or after the
      operation. Postoperative result was perfect after three months of follow up. 

PMID- 24740343
TI  - Catastrophic necrotizing fasciitis after blunt abdominal trauma with delayed
      recognition of the coecal rupture--case report.
AB  - Necrotizing fasciitis (NF) is a rare bacterial infection with dramatic course,
      characterized by widespread necrosis of the skin, subcutaneous tissue, and
      superficial fascia which can often lead to death. We present a case of a 27-year
      old male with NF. One day after experiencing blunt abdominal trauma caused by
      falling over bike handlebars, the patient was admitted to a regional hospital and
      treated for diffuse abdominal pain and large hematoma of the anterior abdominal
      wall. Due to worsening of general condition, he was referred to our hospital the
      following day and operated on urgently. Surgery revealed rupture of the coecum
      with peritonitis and abdominal wall infection. After surgery, fulminant
      necrotizing fasciitis developed. Antibiotics were prescribed according to wound
      cultures and subsequent necrectomies were performed. After 25 days,
      reconstruction of the abdominal wall with skin grafts was obtained. Despite all
      resuscitation measures including fluids, blood transfusions, and parenteral
      nutrition, lung infection and MODS caused death 42 days after initial operation.
      Blunt abdominal trauma can cause the rupture of intestine, and if early signs of
      peritoneal irritation should present, emergency laparotomy should be performed.
      Disastrous complication are rare but lethal. 

PMID- 24740344
TI  - Subcutaneous emphysema, pneumo-orbita and pneumomediastinum following a facial
      trauma caused by a high-pressure car washer.
AB  - Pneumomediastinum is air leakage to mediastinal space from various potential
      sites, including lung, esophagus, trachea, and neck. It is a rare condition that
      develops either spontaneously with increased intraalveolar or intrabronchial
      pressure, or due to trauma. Although cases where face or neck trauma with
      subcutaneous emphysema that extended to mediastinal cavity via anatomical
      connections in face and neck have been reported, orbital traumas leading to
      pneumomediastinum are very rare occurrences that have seldom been reported. This
      paper documents a 17-year-old male who presented with diffuse subcutaneous
      emphysema involving paraorbital facial areas, which extended to neck and
      mediastinal cavity. 

PMID- 24740345
TI  - MRI-guided percutaneous retrograde drilling of osteochondritis dissecans of the
      talus: a feasibility study.
AB  - OBJECTIVES: The purpose of this study was to evaluate the feasibility of MRI
      guidance for percutaneous retrograde drilling in the treatment of osteochondritis
      dissecans of the talus (OCDT). METHODS: Four patients, one juvenile and three
      adults, with one OCDT lesion each and persisting ankle pain after conservative
      treatment, were treated with MRI-guided retrograde drilling. All lesions were
      stable and located in the middle or posterior medial third of the talar dome.
      Pain relief and the ability to return to normal activities were assessed during
      clinical follow-up. MRI and plain film radiographs were used for imaging follow
      up. RESULTS: Technical success was 100% with no complications and with no damage
      to the overlying cartilage. All patients experienced some clinical benefit,
      although only one had complete resolution of pain and one had a relapse leading
      to surgical treatment. Changes in the pathological imaging findings were mostly
      very slight during the follow-up period. CONCLUSIONS: MRI guidance seems
      accurate, safe and technically feasible for retrograde drilling of OCDT. Larger
      series are needed to reliably assess its clinical value. KEY POINTS: * MRI serves
      as a useful guidance method for numerous mini-invasive applications. * Retrograde
      drilling is a cartilage-sparing alternative in the treatment of osteochondritis
      dissecans. * MRI guidance seems feasible for treatment of osteochondritis
      dissecans of the talus.

PMID- 24740346
TI  - Can biochar and phytoextractors be jointly used for cadmium remediation?
AB  - Phytoremediation of soils contaminated with cadmium was tested after liming (CaO)
      or biochar addition, using red amaranth (Amaranthus tricolor L.) as test plant
      species. Two biochars with contrasting characteristics were prepared from two
      feedstocks and added to the soil at a rate of 3% (w:w): Eucalyptus pyrolysed at
      600 degrees C (EB) and poultry litter at 400 degrees C (PLB). Liming was carried
      out in two treatments (CaO1) and (CaO2) to the same pH as the treatments EB and
      PLB respectively. Total plant mass increased in soils amended with PLB and with a
      mixture of PLB and EB; however this was not sufficient to increase the efficiency
      of phytoextraction. Bioavailable and mobile fractions of Cd diminished after
      liming or biochar addition. Our study infers that, both the amount of Cd
      immobilized and the main mechanism responsible for this immobilization varies
      according to biochar properties. 

PMID- 24740347
TI  - Salinomycin potentiates the cytotoxic effects of TRAIL on glioblastoma cell
      lines.
AB  - Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has been reported
      to exhibit therapeutic activity in cancer. However, many tumors remain resistant
      to treatment with TRAIL. Therefore, small molecules that potentiate the cytotoxic
      effects of TRAIL could be used for combinatorial therapy. Here we found that the
      ionophore antibiotic salinomycin acts in synergism with TRAIL, enhancing TRAIL
      induced apoptosis in glioma cells. Treatment with low doses of salinomycin in
      combination with TRAIL augmented the activation of caspase-3 and increased TRAIL
      R2 cell surface expression. TRAIL-R2 upmodulation was required for mediating the
      stimulatory effect of salinomycin on TRAIL-mediated apoptosis, since it was
      abrogated by siRNA-mediated TRAIL-R2 knockdown. Salinomycin in synergism with
      TRAIL exerts a marked anti-tumor effect in nude mice xenografted with human
      glioblastoma cells. Our results suggest that the combination of TRAIL and
      salinomycin may be a useful tool to overcome TRAIL resistance in glioma cells and
      may represent a potential drug for treatment of these tumors. Importantly,
      salinomycin+TRAIL were able to induce cell death of well-defined glioblastoma
      stem-like lines. 

PMID- 24740348
TI  - Endoscopic resection of cystic pontine tumour: three case reports and a proposal
      for minimally invasive dual-endoscopic surgery.
AB  - OBJECTIVE AND IMPORTANCE: We describe a new endoscopic technique, the dual
      endoscopic method, in which two independent endoscopic systems are simultaneously
      used in the subtemporal space and intraparenchymal field for patients with
      pontine cystic tumours. Tumours were successfully removed through a sheath placed
      in the brainstem via the subtemporal keyhole approach, with safety ensured by the
      second subtemporal endoscope. CLINICAL PRESENTATION: A purely endoscopic
      subtemporal approach was performed in three cases of pontine cystic tumour,
      including two low-grade gliomas and a recurrent chordoma. The gliomas showed
      nodules. Recurrent chordoma consisted of a mucinous component. TECHNIQUE: Using a
      keyhole subtemporal approach and a 4.0-mm rigid endoscope with a high-definition
      camera, a transparent puncture needle containing a 2.7-mm rigid endoscope was
      inserted into the cyst. The tumour was removed using suction, biopsy forceps, and
      scissors simultaneously placed with the 2.7-mm endoscope in a transparent sheath.
      CONCLUSION: Since the 4.0-mm endoscope placed in the subtemporal space monitored
      all procedures of the 2.7-mm endoscope, tumour removal was performed safely
      without damaging the pons, cranial nerves, or vessels. We safely and successfully
      removed a cystic pontine tumour using a dual-endoscopic method. This new method
      ensures the safety of deep-seated endoscopic procedures via a minimally invasive
      transcranial approach.

PMID- 24740349
TI  - An evaluation of procedures to increase cooperation related to hoarding in an
      older adult with dementia.
AB  - The prevalence of hoarding (collection of and refusal to discard unneeded items)
      is higher in older adults than the general population and has been correlated
      with dementia. Treatments to increase cooperation with discarding hoarded items
      have not been systematically evaluated. This study evaluated two procedures for
      increasing cooperation with handing over hoarded items in an older adult with
      dementia. The antecedent-based intervention effectively increased cooperation. 

PMID- 24740350
TI  - Drug samples in dermatology: out of the closet, into the dustbin.

PMID- 24740351
TI  - Release of mobile forms of hazardous elements from glassworks fly ash into soils.
AB  - The release of hazardous elements from the wastes of high-temperature processes
      represents a risk to the environment. We focused on the alteration of fly ash
      (FA) from glassworks collected from an electrostatic filter. FA contains elevated
      concentrations of Zn and Ba, among other elements. Overtime, small amounts of FA
      have been emitted from the factory and settled into the surrounding environment
      (soil). In order to assess the possible risks to the environment, samples of FA
      were placed in small nylon bags and deposited in 11 different soil horizons
      (containing diverse vegetation cover such as spruce and beech and also unforested
      areas). Samples of the FA in bags were exposed in the soils for 1 year. Then, the
      bags were collected, and the exposed soils in the direct vicinity of the FA bags
      were sampled. The total concentrations of Zn and Ba in the FA, as well as in the
      soil samples (original and exposed), were determined by ICP MS. The "mobile
      fraction" was determined as the exchangeable (acid extractable) fraction of the
      modified BCR sequential extraction procedure (SEP). The SEP results indicate that
      Zn and Ba may pose a potential environmental risk. Their concentrations in the
      first, most mobile, and bioavailable fraction increased in all the exposed soils.
      The most significant increases were observed in the upper soil horizons (litter
      and A horizon). The risk to the environment was evaluated on the basis of the
      Risk Assessment Code.

PMID- 24740352
TI  - [The new DSM 5 classification system: essential amendments in the psychiatric
      classification].

PMID- 24740353
TI  - [Schizophrenia and other psychotic disorders in DSM-5: summary of the changes
      compared to DSM-IV].
AB  - With the introduction of the fifth edition of the Diagnostic and Statistical
      Manual of Mental Disorders (DSM-5) numerous changes in the area of the
      schizophrenia spectrum and psychotic disorders have been implemented.
      Establishing a metastructure based on the characteristics of the spectrum of
      psychopathological disturbances should improve clarity. The classical subtypes of
      schizophrenia were eliminated and specific psychopathological dimensions for the
      assessment of disease severity were added. The special role of Schneiderian first
      rank symptoms was abandoned and a higher delineation towards schizoaffective
      disorders is made. The nosological status of catatonia is clarified and occurs
      together with a consistent use of catatonic disturbances over all chapters. The
      attenuated psychosis syndrome is added as a new condition for further study. The
      shared psychotic disorder in the sense of a folie a deux is no longer maintained.
      However, the initial goal to integrate more disorder-specific etiopathogenetic
      information into the reconceptualization could not be achieved. Contemporaneously
      to the development process of DSM-5 the National Institute of Mental Health
      (NIMH) carried out the research domain criteria project (RDoC) attempting to
      incorporate the current growth in knowledge of genetics, neurocognitive and
      cognitive sciences in future diagnostic systems. This article gives an overview
      of the changes that have been made within the revision process from DSM-IV to DSM
      5. 

PMID- 24740355
TI  - Directed self-assembly of block copolymers: a tutorial review of strategies for
      enabling nanotechnology with soft matter.
AB  - Self-assembly of soft materials is broadly considered an attractive means of
      generating nanoscale structures and patterns over large areas. However, the
      spontaneous formation of equilibrium nanostructures in response to temperature
      and concentration changes, for example, must be guided to yield the long-range
      order and orientation required for utility in a given scenario. In this review we
      examine directed self-assembly (DSA) of block copolymers (BCPs) as canonical
      examples of nanostructured soft matter systems which are additionally compelling
      for creating functional materials and devices. We survey well established and
      newly emerging DSA methods from a tutorial perspective. Special emphasis is given
      to exploring underlying physical phenomena, identifying prototypical BCPs that
      are compatible with different DSA techniques, describing experimental methods and
      highlighting the attractive functional properties of block copolymers overall.
      Finally we offer a brief perspective on some unresolved issues and future
      opportunities in this field. 

PMID- 24740354
TI  - Recurrent salivary pleomorphic adenoma shows increased immunohistologic
      expression of bcl-2 oncoprotein.
AB  - BACKGROUND: Internal cell biology, including apoptotic regulation, is presumed to
      play a key role in the development of recurrent pleomorphic adenoma (PA). AIM:
      The aim of our study was to determine the relevance of B-cell lymphoma 2 (bcl-2)
      oncoprotein immunoexpression and distribution in primary PA, and its recurrence.
      METHODS: Ten primary-non-recurrent, 14 primary-to-recur, and 28 recurrences of
      parotid PA patients aged 19-73 (mean 40.7+/-16.7) years were enrolled. The bcl-2
      expression was compared between groups using a semi-quantitative histoscore,
      defined as the multiple of the percentage of cells by the intensity of
      immunostaining. RESULTS: Widely varying bcl-2 immunoreaction was found in the
      epithelial areas of 91.7% of primary and 85.2% of recurrent PA. Similarly varying
      but much less, immunopositivity was found in the myxoid areas of 62.5% of primary
      and 71.4% of recurrent tumours. No obvious differences in the bcl-2 staining
      intensity or pattern of specific epithelial morphologic structures in either the
      primary-non-recurrent, primary-to-recur or recurrent tumours were found. In both
      the mesenchymal and epithelial areas of PA, the differences in bcl-2
      immunohistoscore between the primary-non-recurrent and primary-to-recur groups
      were not statistically significant (P=0.62, respectively 0.51). In the
      mesenchymal areas, the study revealed a significantly increased histoscore in
      recurrent tumours compared to their corresponding primaries (P=0.01). Increased
      bcl-2 expression in recurrent PA suggests an exaggerated aggressiveness of that
      tumor. CONCLUSION: The fact that a significant difference in the histoscore was
      found exclusively in the myxoid component seems to accord with the reported
      prevalence of the latter in recurrent and metastatic PA.

PMID- 24740356
TI  - Biochemical and kinetic study of laccase from Ganoderma cupreum AG-1 in
      hydrogels.
AB  - In the present study, three different types of hydrogels i.e., (poly (
      acrylamide)/alginate (P (AAm)/Alg), poly (acrylamide-N-isopropylacrylamide) (P
      (AAm-NIPA)), and poly (acrylamide-N-isopropylacrylamide)/alginate (P (AAm
      NIPA)/Alg)) were synthesized by acrylamide, alginate, and N-isopropylacrylamide
      for the entrapment of laccase. The hydrogel-entrapped and free laccase showed
      optimum temperature of 50  degrees C for the oxidation of ABTS, but the entrapped
      laccase showed high temperature, pH, and storage stability as compared to the
      free enzyme. The K m values of free laccase, (P (AAm)/Alg)-L, (P (AAm-NIPA))-L,
      and (P (AAm-NIPA)/Alg)-L were found to be 0.13, 0.28, 0.33, and 0.50 mM,
      respectively. The V max values of free laccase, (P (AAm)/Alg)-L, (P (AAm-NIPA))
      L, and (P (AAm-NIPA)/Alg)-L were found to be 22.22 * 10(2), 5.55 * 10(2), 5.0 *
      10(2), and 4.54 * 10(2) mM/min, respectively. The entrapped laccase hydrogels
      were used for the decolorization of Reactive Violet 1 dye, with 39 to 45 %
      decolorization efficiency till the 10th cycle. 

PMID- 24740357
TI  - Isolation and identification of alpha-glucosidase and protein glycation
      inhibitors from Stereospermum colais.
AB  - Stereospermum colais (family Bignoniaceae) is a well-known pharmacologically
      potent medicinal plant reported in traditional systems of medicine. Phytochemical
      investigation of the roots of S. colais resulted in the isolation of seven
      compounds, and the metabolites were screened for its alpha-glucosidase enzyme
      inhibition and anti-glycation property. The compounds identified were beta
      sitosterol (1), 2-(4'-hydroxyphenyl) ethyl undecanoate (2), 2-(4'
      hydroxyphenyl)ethyl pentadecanoate (3), 5alpha-ergosta-7,22-dien-3beta-ol (4),
      ursolic acid (5), lapachol (6), and pinoresinol (7). Ursolic acid, lapachol, and
      pinoresinol possessed IC50 values of 119.01, 130.29, and 125.62 nM, respectively,
      compared to standard ascorbic acid with an IC50 value of 201.01 nM. The other
      compounds failed to show the activity. Results of the current study showcased the
      possible exploration of this medicinal plant for the treatment of type 2 diabetes
      in line with the development of phytopharmaceutical industry. 

PMID- 24740358
TI  - Development of a functional ruthenium(II) complex for probing hypochlorous acid
      in living cells.
AB  - A functional ruthenium(ii) complex, [Ru(bpy)2(AN-bpy)](PF6)2 (bpy: 2,2'
      bipyridine, AN-bpy: 4-methyl-4'-(4-amino-3-nitro-phenoxy-methylene)-2,2'
      bipyridine), has been designed and synthesized as a turn-on luminescent probe for
      the imaging of hypochlorous acid (HOCl) in living cells. Due to the
      intramolecular photoinduced electron transfer (PET), the ruthenium(ii) complex
      itself is almost non-luminescent. However, it can specifically and rapidly react
      with HOCl in aqueous media to afford a highly luminescent derivative,
      [Ru(bpy)2(HM-bpy)](PF6)2 (HM-bpy: 4-hydroxymethyl-4'-methyl-2,2'-bipyridine),
      accompanied by a 110-fold luminescence enhancement. Taking advantage of high
      specificity and sensitivity, and excellent photophysical properties of the
      ruthenium(ii) complex probe, [Ru(bpy)2(AN-bpy)](PF6)2 was successfully applied to
      the luminescence imaging of the exogenous HOCl in living HeLa cells and the
      endogenous HOCl in porcine neutrophils. The results corroborate that indeed
      [Ru(bpy)2(AN-bpy)](PF6)2 is a useful luminescent probe for the monitoring of HOCl
      in biological systems. 

PMID- 24740360
TI  - Inferring rare disease risk variants based on exact probabilities of sharing by
      multiple affected relatives.
AB  - MOTIVATION: Family-based designs are regaining popularity for genomic sequencing
      studies because they provide a way to test cosegregation with disease of variants
      that are too rare in the population to be tested individually in a conventional
      case-control study. RESULTS: Where only a few affected subjects per family are
      sequenced, the probability that any variant would be shared by all affected
      relatives-given it occurred in any one family member-provides evidence against
      the null hypothesis of a complete absence of linkage and association. A P-value
      can be obtained as the sum of the probabilities of sharing events as (or more)
      extreme in one or more families. We generalize an existing closed-form expression
      for exact sharing probabilities to more than two relatives per family. When
      pedigree founders are related, we show that an approximation of sharing
      probabilities based on empirical estimates of kinship among founders obtained
      from genome-wide marker data is accurate for low levels of kinship. We also
      propose a more generally applicable approach based on Monte Carlo simulations. We
      applied this method to a study of 55 multiplex families with apparent non
      syndromic forms of oral clefts from four distinct populations, with whole exome
      sequences available for two or three affected members per family. The rare single
      nucleotide variant rs149253049 in ADAMTS9 shared by affected relatives in three
      Indian families achieved significance after correcting for multiple comparisons
      ([Formula: see text]). AVAILABILITY AND IMPLEMENTATION: Source code and binaries
      of the R package RVsharing are freely available for download at http://cran.r
      project.org/web/packages/RVsharing/index.html. CONTACT:
      alexandre.bureau@msp.ulaval.ca or ingo@jhu.edu SUPPLEMENTARY INFORMATION:
      Supplementary data are available at Bioinformatics online.

PMID- 24740361
TI  - Molecular cloning, characterization and functional assessment of the myosin light
      polypeptide chain 2 (mylz2) promoter of farmed carp, Labeo rohita.
AB  - We cloned the 5'-flanking region (1.2 kb) of a muscle-specific gene, encoding
      myosin light chain 2 polypeptide (mylz2) of a farmed carp, Labeo rohita (rohu).
      Sequence analysis using TRANSFAC-database search identified the consensus cis
      acting regulatory elements of TATA-box and E (CANNTG)-box, including the monocyte
      enhancer factor 2 motif, implying that it is likely to be a functional promoter.
      The proximal promoter (~620 bp) was highly homologous with that of Danio rerio
      (zebrafish) as compared to Channa striatus (snakehead murrel) counterparts and
      showed less identity with Sparus auratus (gilthead sea bream), Xenopus laevis
      (African clawed frog) and Rattus norvegicus (Norway rat). Direct muscular
      (skeletal) injection of the construct containing the mylz2 promoter (0.6 kb)
      fused to a green fluorescent protein (GFP) reporter gene showed efficient
      expression in L. rohita, validating its functional activity. Further, the
      functional activity was confirmed by the observation that this promoter drove GFP
      expression in the skeletal muscle of transgenic rohu. The promoter may have
      potential applications for value-addition in ornamental fishes and studying gene
      regulatory functions. 

PMID- 24740359
TI  - Mapping the genetic architecture of gene regulation in whole blood.
AB  - BACKGROUND: We aimed to assess whether whole blood expression quantitative trait
      loci (eQTLs) with effects in cis and trans are robust and can be used to identify
      regulatory pathways affecting disease susceptibility. MATERIALS AND METHODS: We
      performed whole-genome eQTL analyses in 890 participants of the KORA F4 study and
      in two independent replication samples (SHIP-TREND, N = 976 and EGCUT, N = 842)
      using linear regression models and Bonferroni correction. RESULTS: In the KORA F4
      study, 4,116 cis-eQTLs (defined as SNP-probe pairs where the SNP is located
      within a 500 kb window around the transcription unit) and 94 trans-eQTLs reached
      genome-wide significance and overall 91% (92% of cis-, 84% of trans-eQTLs) were
      confirmed in at least one of the two replication studies. Different study designs
      including distinct laboratory reagents (PAXgeneTM vs. TempusTM tubes) did not
      affect reproducibility (separate overall replication overlap: 78% and 82%).
      Immune response pathways were enriched in cis- and trans-eQTLs and significant
      cis-eQTLs were partly coexistent in other tissues (cross-tissue similarity 40
      70%). Furthermore, four chromosomal regions displayed simultaneous impact on
      multiple gene expression levels in trans, and 746 eQTL-SNPs have been previously
      reported to have clinical relevance. We demonstrated cross-associations between
      eQTL-SNPs, gene expression levels in trans, and clinical phenotypes as well as a
      link between eQTLs and human metabolic traits via modification of gene regulation
      in cis. CONCLUSIONS: Our data suggest that whole blood is a robust tissue for
      eQTL analysis and may be used both for biomarker studies and to enhance our
      understanding of molecular mechanisms underlying gene-disease associations.

PMID- 24740363
TI  - The ACA Marketplace.

PMID- 24740362
TI  - Maternal plasma RNA sequencing for genome-wide transcriptomic profiling and
      identification of pregnancy-associated transcripts.
AB  - BACKGROUND: Analysis of circulating RNA in the plasma of pregnant women has the
      potential to serve as a powerful tool for noninvasive prenatal testing and
      research. However, detection of circulating RNA in the plasma in an unbiased and
      high-throughput manner has been technically challenging. Therefore, only a
      limited number of circulating RNA species in maternal plasma have been validated
      as pregnancy- and placenta-specific biomarkers. METHODS: We explored the use of
      massively parallel sequencing for plasma transcriptome profiling in first-,
      second-, and third-trimester pregnant women. Genotyping was performed for
      amniotic fluid, placental tissues, and maternal blood cells, with exome-enriched
      sequencing. RESULTS: In the early pregnancy group comprising 1 first- and 1
      second-trimester pregnancy cases, the fetal contribution to the RNA pool in
      maternal plasma was 3.70%. The relative proportion of fetal contribution was
      increased to 11.28% in the late pregnancy group comprising 2 third-trimester
      pregnancy cases. The placental biallelic expression pattern of PAPPA (pregnancy
      associated plasma protein A, pappalysin 1), a known pregnancy-specific gene, and
      the monoallelic expression pattern of H19 [H19, imprinted maternally expressed
      transcript (non-protein coding)], an imprinted maternally expressed gene, were
      also detected in the maternal plasma. Furthermore, by direct examination of the
      maternal plasma transcriptomic profiles before and after delivery, we identified
      a panel of pregnancy-associated genes. CONCLUSIONS: Plasma RNA sequencing
      provides a holistic view of the maternal plasma transcriptomic repertoire. This
      technology is potentially valuable for using circulating plasma nucleic acids for
      prenatal testing and research.

PMID- 24740364
TI  - Learning curve.

PMID- 24740365
TI  - Breaking down barriers.

PMID- 24740366
TI  - So "appy" together.

PMID- 24740367
TI  - Turning the tables on health.

PMID- 24740368
TI  - Team effort.

PMID- 24740369
TI  - Exome sequencing in single cells from the cerebrospinal fluid in multiple
      sclerosis.
AB  - BACKGROUND: Genome-wide association studies (GWAS) have identified over 100
      germline variants that influence susceptibility to multiple sclerosis, most of
      which map within or near to genes with immunological function. However, the role
      of somatic mutations in multiple sclerosis has not been investigated. OBJECTIVE:
      The objective of this paper is to explore the role that somatic mutations might
      play in the development of multiple sclerosis. METHODS: We exome-sequenced in
      total 21 individual CD4+ lymphocytes isolated from cerebrospinal fluid of two
      patients. In addition we sequenced DNA from the patients' peripheral blood to
      serve as germline reference. RESULTS: In comparison with the respective germline
      sequence, each cell differed at an average of 1784 positions, but as anticipated
      subsequent analysis confirms that most, if not all, of these potential mutations
      are likely to represent artefacts generated during the amplification of a single
      genome and/or by sequencing. Fifty-six of the potential mutations were predicted
      to have likely functional effects on genes that have previously been implicated
      by GWAS, including three in the CD6 gene. CONCLUSION: More robust methods applied
      to larger numbers of cells will be needed to define the role of somatic
      mutations.

PMID- 24740370
TI  - Forceps minor damage and co-occurrence of depression and fatigue in multiple
      sclerosis.
AB  - OBJECTIVE: Using diffusion tensor magnetic resonance imaging (DT MRI), we
      analyzed the architectural integrity of the brain white matter (WM) from a large
      cohort of MS patients to identify the structural substrates of the concomitant
      presence of depression and fatigue. METHODS: Brain dual-echo, 3D T1-weighted and
      DT MRI scans were acquired from 147 MS patients and 90 gender- and age-matched
      healthy controls (HCs). Patients were stratified by the presence of depression
      (92 depressed (D), 55 not depressed (nD)) and fatigue (81 fatigued (F), 66 not
      fatigued (nF)). Sixty-five patients had co-occurrence of depression and fatigue
      (DF). Whole-brain voxel-wise comparisons of WM DT MRI abnormalities were
      performed using tract-based-spatial-statistics (TBSS). Tract-specific analyses
      were run in brain WM tracts using standard-space templates. RESULTS: Whole-brain
      voxel-wise analysis yielded no significant differences between patient subgroups.
      At tract-specific analysis, DF patients had reduced fractional anisotropy (FA) of
      the forceps minor. Reduced FA of the right anterior thalamic radiation and right
      uncinate fasciculus was found in F-MS vs not F-MS patients after correcting for
      depression. No significant differences were found between D vs not D-MS patients,
      after correcting for fatigue. CONCLUSIONS: This study provides evidence for
      partially overlapping damage to frontal and fronto-temporal pathways underlying
      depression and fatigue in MS.

PMID- 24740372
TI  - Synthesis of heterocyclic-fused benzopyrans via the Pd(II)-catalyzed C-H
      alkenylation/C-O cyclization of flavones and coumarins.
AB  - An efficient and practical method for effecting a tandem C-H alkenylation/C-O
      cyclization has been achieved via the C-H functionalization of flavone
      derivatives. The synthetic utility of the one-pot sequence was demonstrated by
      obtaining convenient access to coumarin-annelated benzopyrans. The reaction scope
      for the transformation was found to be fairly broad, affording good yields of a
      wide range of flavone- or coumarin-fused benzopyran motifs, which are privileged
      structures in many biologically active compounds. 

PMID- 24740371
TI  - Responder definition of the Multiple Sclerosis Impact Scale physical impact
      subscale for patients with physical worsening.
AB  - BACKGROUND: The 29-item Multiple Sclerosis Impact Scale (MSIS-29) was developed
      to examine the impact of multiple sclerosis (MS) on physical and psychological
      functioning from a patient's perspective. OBJECTIVE: To determine the responder
      definition (RD) of the MSIS-29 physical impact subscale (PHYS) in a group of
      patients with relapsing-remitting MS (RRMS) participating in a clinical trial.
      METHODS: Data from the SELECT trial comparing daclizumab high-yield process with
      placebo in patients with RRMS were used. Physical function was evaluated in
      SELECT using three patient-reported outcomes measures and the Expanded Disability
      Status Scale (EDSS). Anchor- and distribution-based methods were used to identify
      an RD for the MSIS-29. RESULTS: Results across the anchor-based approach
      suggested MSIS-29 PHYS RD values of 6.91 (mean), 7.14 (median) and 7.50 (mode).
      Distribution-based RD estimates ranged from 6.24 to 10.40. An RD of 7.50 was
      selected as the most appropriate threshold for physical worsening based on
      corresponding changes in the EDSS (primary anchor of interest). CONCLUSION: These
      findings indicate that a >=7.50 point worsening on the MSIS-29 PHYS is a
      reasonable and practical threshold for identifying patients with RRMS who have
      experienced a clinically significant change in the physical impact of MS.

PMID- 24740373
TI  - Preparation, characterization, and in vitro cytotoxicity evaluation of a novel
      anti-tuberculosis reconstruction implant.
AB  - BACKGROUND: Reconstruction materials currently used in clinical for
      osteoarticular tuberculosis (TB) are unsatisfactory due to a variety of reasons.
      Rifampicin (RFP) is a well-known and highly effective first-line anti
      tuberculosis (anti-TB) drug. Poly-DL-lactide (PDLLA) and nano-hydroxyapatite
      (nHA) are two promising materials that have been used both for orthopedic
      reconstruction and as carriers for drug release. In this study we report the
      development of a novel anti-TB implant for osteoarticular TB reconstruction using
      a combination of RFP, PDLLA and nHA. METHODS: RFP, PDLLA and nHA were used as
      starting materials to produce a novel anti-TB activity implant by the solvent
      evaporation method. After manufacture, the implant was characterized and its
      biodegradation and drug release profile were tested. The in vitro cytotoxicity of
      the implant was also evaluated in pre-osteoblast MC3T3-E1 cells using multiple
      methodologies. RESULTS: A RFP/PDLLA/nHA composite was successfully synthesized
      using the solvent evaporation method. The composite has a loose and porous
      structure with evenly distributed pores. The production process was steady and no
      chemical reaction occurred as proved by Fourier Transform Infrared Spectroscopy
      (FTIR) and X-Ray Diffraction (XRD). Meanwhile, the composite blocks degraded and
      released drug for at least 12 weeks. Evaluation of in vitro cytotoxicity in MC3T3
      E1 cells verified that the synthesized composite blocks did not affect cell
      growth and proliferation. CONCLUSION: It is feasible to manufacture a novel
      bioactive anti-TB RFP/PDLLA/nHA composite by the solvent evaporation method. The
      composite blocks showed appropriate properties such as degradation, drug release
      and biosafety to MC3T3-E1 cells. In conclusion, the novel composite blocks may
      have great potential for clinical applications in repairing bone defects caused
      by osteoarticular TB.

PMID- 24740374
TI  - A laboratory comparison of two variations of differential-reinforcement-of-low
      rate procedures.
AB  - We compared 2 variations of differential-reinforcement-of-low-rate (DRL)
      procedures: spaced-responding DRL, in which a reinforcer was delivered contingent
      on each response if a specified interval had passed since the last response, and
      full-session DRL, in which a reinforcer was presented at the end of an interval
      if the response rate was below criterion within the specified interval. We used a
      human-operant procedure and analyzed within-session responding to assess any
      similarities or differences between procedures. Data revealed a positive
      contingency between responding and reinforcement under the spaced-responding DRL
      schedule and a negative contingency under the full-session DRL schedule.
      Furthermore, 60% of the participants discontinued responding by the last full
      session DRL session. Implications for the appropriate procedural and taxonomical
      usage of both DRL schedules are discussed. 

PMID- 24740377
TI  - Exaggerated earlobe ptosis due to habitual ear pulling.

PMID- 24740375
TI  - Strong vaccine-induced CD8 T-cell responses have cytolytic function in a
      chimpanzee clearing HCV infection.
AB  - A single correlate of effective vaccine protection against chronic HCV infection
      has yet to be defined. In this study, we analyzed T-cell responses in four
      chimpanzees, immunized with core-E1-E2-NS3 and subsequently infected with HCV1b.
      Viral clearance was observed in one animal, while the other three became
      chronically infected. In the animal that cleared infection, NS3-specific CD8 T
      cell responses were observed to be more potent in terms of frequency and
      polyfunctionality of cytokine producing cells. Unique to this animal was the
      presence of killing-competent CD8 T-cells, specific for NS3 1258-1272, being
      presented by the chimpanzee MHC class I molecule Patr-A*03?01, and a high
      affinity recognition of this epitope. In the animals that became chronically
      infected, T-cells were able to produce cytokines against the same peptide but no
      cytolysis could be detected. In conclusion, in the animal that was able to clear
      HCV infection not only cytokine production was observed but also cytolytic
      potential against specific MHC class I/peptide-combinations.

PMID- 24740378
TI  - Escherichia coli RIC is able to donate iron to iron-sulfur clusters.
AB  - Escherichia coli RIC (Repair of Iron Centers) is a diiron protein previously
      reported to be involved in the repair of iron-sulfur proteins damaged by
      oxidative or nitrosative stresses, and proposed to act as an iron donor. This
      possible role of RIC was now examined specifically by evaluating its ability to
      donate iron ions to apo-iron-sulfur proteins, determining the iron binding
      constants and assessing the lability of its iron ions. We show, by UV-visible,
      EPR and resonance Raman spectroscopies that RIC may participate in the synthesis
      of an iron-sulfur cluster in the apo-forms of the spinach ferredoxin and IscU
      when in the presence of the sulfide donating system IscS and L-cysteine. Iron
      binding assays allowed determining the as-isolated and fully reduced RIC
      dissociation constants for the ferric and ferrous iron of 10-27 M and 10-13 M,
      respectively. Mossbauer studies revealed that the RIC iron ions are labile,
      namely when the center is in the mixed-valence redox form as compared with the
      (MU-oxo) diferric one. Altogether, these results suggest that RIC is capable of
      delivering iron for the formation of iron-sulfur clusters. 

PMID- 24740379
TI  - Enhanced inflammatory potential of CD4+ T-cells that lack proteasome
      immunosubunit expression, in a T-cell transfer-based colitis model.
AB  - Proteasomes play a fundamental role in intracellular protein degradation and
      therewith regulate a variety of cellular processes. Exposure of cells to
      (pro)inflammatory cytokines upregulates the expression of three inducible
      catalytic proteasome subunits, the immunosubunits, which incorporate into newly
      assembled proteasome complexes and alter the catalytic activity of the cellular
      proteasome population. Single gene-deficient mice lacking one of the three
      immunosubunits are resistant to dextran sulfate sodium (DSS)-induced colitis
      development and, likewise, inhibition of one single immunosubunit protects mice
      against the development of DSS-induced colitis. The observed diminished disease
      susceptibility has been attributed to altered cytokine production and CD4+ T-cell
      differentiation in the absence of immunosubunits. To further test whether the
      catalytic activity conferred by immunosubunits plays an essential role in CD4+ T
      cell function and to distinguish between the role of immunosubunits in effector T
      cells versus inflamed tissue, we used a T-cell transfer-induced colitis model.
      Naive wt or immunosubunit-deficient CD4+ T-cells were adoptively transferred into
      RAG1-/- and immunosubunit-deficient RAG1-/- mice and colitis development was
      determined six weeks later. While immunosubunit expression in recipient mice had
      no effect on colitis development, transferred immunosubunit-deficient T- cells
      were more potent in inducing colitis and produced more proinflammatory IL17 than
      wt T-cells. Taken together, our data show that modifications in proteasome
      mediated proteolysis in T-cells, conferred by lack of immunosubunit
      incorporation, do not attenuate but enhance CD4+ T-cell-induced inflammation. 

PMID- 24740380
TI  - The "naked coral" hypothesis revisited--evidence for and against scleractinian
      monophyly.
AB  - The relationship between Scleractinia and Corallimorpharia, Orders within
      Anthozoa distinguished by the presence of an aragonite skeleton in the former, is
      controversial. Although classically considered distinct groups, some phylogenetic
      analyses have placed the Corallimorpharia within a larger
      Scleractinia/Corallimorpharia clade, leading to the suggestion that the
      Corallimorpharia are "naked corals" that arose via skeleton loss during the
      Cretaceous from a Scleractinian ancestor. Scleractinian paraphyly is, however,
      contradicted by a number of recent phylogenetic studies based on mt nucleotide
      (nt) sequence data. Whereas the "naked coral" hypothesis was based on analysis of
      the sequences of proteins encoded by a relatively small number of mt genomes,
      here a much-expanded dataset was used to reinvestigate hexacorallian phylogeny.
      The initial observation was that, whereas analyses based on nt data support
      scleractinian monophyly, those based on amino acid (aa) data support the "naked
      coral" hypothesis, irrespective of the method and with very strong support. To
      better understand the bases of these contrasting results, the effects of
      systematic errors were examined. Compared to other hexacorallians, the mt genomes
      of "Robust" corals have a higher (A+T) content, codon usage is far more
      constrained, and the proteins that they encode have a markedly higher
      phenylalanine content, leading us to suggest that mt DNA repair may be impaired
      in this lineage. Thus the "naked coral" topology could be caused by high levels
      of saturation in these mitochondrial sequences, long-branch effects or model
      violations. The equivocal results of these extensive analyses highlight the
      fundamental problems of basing coral phylogeny on mitochondrial sequence data. 

PMID- 24740381
TI  - Syncopation, body-movement and pleasure in groove music.
AB  - Moving to music is an essential human pleasure particularly related to musical
      groove. Structurally, music associated with groove is often characterised by
      rhythmic complexity in the form of syncopation, frequently observed in musical
      styles such as funk, hip-hop and electronic dance music. Structural complexity
      has been related to positive affect in music more broadly, but the function of
      syncopation in eliciting pleasure and body-movement in groove is unknown. Here we
      report results from a web-based survey which investigated the relationship
      between syncopation and ratings of wanting to move and experienced pleasure.
      Participants heard funk drum-breaks with varying degrees of syncopation and audio
      entropy, and rated the extent to which the drum-breaks made them want to move and
      how much pleasure they experienced. While entropy was found to be a poor
      predictor of wanting to move and pleasure, the results showed that medium degrees
      of syncopation elicited the most desire to move and the most pleasure,
      particularly for participants who enjoy dancing to music. Hence, there is an
      inverted U-shaped relationship between syncopation, body-movement and pleasure,
      and syncopation seems to be an important structural factor in embodied and
      affective responses to groove. 

PMID- 24740382
TI  - Going with the flow: a brief history of the study of the honeybee's navigational
      'odometer'.
AB  - Honeybees navigate to a food source using a sky-based compass to determine their
      travel direction, and an odometer to register how far they have travelled. The
      past 20 years have seen a renewed interest in understanding the nature of the
      odometer. Early work, pioneered by von Frisch and colleagues, hypothesized that
      travel distance is measured in terms of the energy that is consumed during the
      journey. More recent studies suggest that visual cues play a role as well.
      Specifically, bees appear to gauge travel distance by sensing the extent to which
      the image of the environment moves in the eye during the journey from the hive to
      the food source. Most of the evidence indicates that travel distance is measured
      during the outbound journey. Accumulation of odometric errors is restricted by
      resetting the odometer every time a prominent landmark is passed. When making
      detours around large obstacles, the odometer registers the total distance of the
      path that is flown to the destination, and not the "bee-line" distance. Finally,
      recent studies are revealing that bees can perform odometry in three dimensions. 

PMID- 24740383
TI  - Sensory-evoked turning locomotion in red-eared turtles: kinematic analysis and
      electromyography.
AB  - We examined the limb kinematics and motor patterns that underlie sensory-evoked
      turning locomotion in red-eared turtles. Intact animals were held by a band-clamp
      in a water-filled tank. Turn-swimming was evoked by slowly rotating turtles to
      the right or left via a motor connected to the shaft of the band-clamp. Animals
      executed sustained forward turn-swimming against the direction of the imposed
      rotation. We recorded video of turn-swimming and computer-analyzed the limb and
      head movements. In a subset of turtles, we also recorded electromyograms from
      identified limb muscles. Turning exhibited a stereotyped pattern of (1)
      coordinated forward swimming in the hindlimb and forelimb on the outer side of
      the turn, (2) back-paddling in the hindlimb on the inner side, (3) a nearly
      stationary, "braking" forelimb on the inner side, and (4) neck bending toward the
      direction of the turn. Reversing the rotation caused animals to switch the
      direction of their turns and the asymmetric pattern of right and left limb
      activities. Preliminary evidence suggested that vestibular inputs were sufficient
      to drive the behavior. Sensory-evoked turning may provide a useful experimental
      platform to examine the brainstem commands and spinal neural networks that
      underlie the activation and switching of different locomotor forms. 

PMID- 24740384
TI  - Asymmetric synthesis of chloroisothreonine derivatives via syn-stereoselective
      Mannich-type additions across N-sulfinyl-alpha-chloroimines.
AB  - Mannich-type reactions of O-Boc glycolic esters across chiral N-sulfinyl-alpha
      chloroaldimines resulted in the efficient and syn-stereoselective synthesis of
      new gamma-chloro-alpha-hydroxy-beta-amino esters (dr > 99 : 1). The alpha
      coordinating ability of the chlorine atom was of great importance for the
      diastereoselectivity of the Mannich-type reaction and overruled the chelation of
      the sulfinyl oxygen with the lithium ion of the incoming E-enolate in the
      transition state model. These novel chloroisothreonine derivatives proved to be
      excellent building blocks in asymmetric synthesis of novel syn-beta,gamma
      aziridino-alpha-hydroxy esters and biologically relevant trans-oxazolidinone
      carboxylic esters. 

PMID- 24740385
TI  - Capillary attraction induced collapse of colloidal monolayers at fluid
      interfaces.
AB  - We investigate the evolution of a system of colloidal particles, trapped at a
      fluid interface and interacting via capillary attraction, as a function of the
      range of capillary interactions and temperature. We address the collapse of an
      initially homogeneous particle distribution and of a radially symmetric (disk
      shaped) distribution of finite size, both theoretically by using a perturbative
      approach inspired by cosmological models and numerically by means of Brownian
      dynamics (BD) and dynamical density functional theory (DDFT). The results are
      summarized in a "dynamical phase diagram", describing a smooth crossover from a
      collective (gravitational-like) collapse to local (spinodal-like) clustering. In
      this crossover region, the evolution exhibits a peculiar shock wave behavior at
      the outer rim of the contracting, disk-shaped distribution. 

PMID- 24740387
TI  - Complete genomic sequence of the coronavirus transmissible gastroenteritis virus
      SHXB isolated in China.
AB  - A strain of transmissible gastroenteritis virus (TGEV), SHXB, was isolated in
      Shanghai, China. The complete genome of strain SHXB was sequenced, and its
      sequence was compared those of other TGEV strains in the GenBank database. The
      comparison showed that there were no insertions or deletions in the 5' and 3'-
      non-translated regions, in the nonstructural genes ORF1, ORF3, and ORF7, or in
      the genes encoding the structural proteins envelope (E), membrane (M) and
      nucleoprotein (N). A phenomenon in common with other strains was that nucleotide
      (nt) 655 of the spike (S) gene was G, and a common change in nt 1753 of the S
      gene was a T-to-G mutation that caused a serine-to-alanine mutation at amino acid
      585, which is in the region of the main major antigenic sites A and B of the TGEV
      S protein. A 6-nt deletion was also found at nt 1123-1128 in all Purdue strains
      except the strain Virulent Purdue. Phylogenetic analysis showed that TGEV SHXB
      was closely related to the Purdue strains and shared a common ancestor with the
      Miller strains as well as strain PRCV-ISU-1. 

PMID- 24740388
TI  - Comparison of starch granule development and physicochemical properties of
      starches in wheat pericarp and endosperm.
AB  - BACKGROUND: The objectives of this study were: (i) to characterize structural
      development of starch granule in pericarp and endosperm during wheat caryopsis
      growth; (ii) to compare physicochemical properties of starches in pericarp and
      endosperm; (iii) to further discover the relationships between pericarp starches
      and endosperm starches. Wheat pericarp and endosperm at different development
      stages were observed by light microscopy and scanning electron microscopy,
      respectively. Structural properties of starches were determined using X-ray power
      diffraction and (13) C solid nuclear magnetic resonance. RESULTS: Pericarp starch
      granules (PSG) accumulated in amyloplasts and chloroplasts, and showed a typical
      accumulation peak at 5 days after fertilization (DAF), and then gradually
      decomposed during 5-22 DAF. PSG in the abdominal region showed a higher rate of
      decomposition compared to the dorsal region of pericarp. Endosperm starch
      granules (ESG) accumulated in amyloplasts, and occurred in endosperm cells at 5
      DAF, then rapidly enriched the endosperm cells until 22 DAF. Compared with ESG,
      PSG were compound granules of irregular shape and small size distribution. The
      results also suggested lower amylose content and V-type single-helix content and
      higher proportions of double helices for PSG compared to ESG. CONCLUSION: Based
      on the structural development of PSG and ESG, we speculated that the saccharides
      resulting from decomposition of PSG, on one hand, enabled the pericarp to survive
      before maturity of wheat caryopsis and, on the other hand, provided extra
      nutrition for the growth of ESG.

PMID- 24740389
TI  - Lognormality of trace contaminant concentrations in sewage effluents.
AB  - It is important to understand the statistical distribution of monitoring data for
      them to be of value in determining the parameters of environmental models. No
      such distributional information has been available for many trace contaminants in
      sewage effluents. This paper applies the data of a major UK sewage works'
      effluent monitoring programme to determine the validity of the common assumption
      that data are lognormally distributed. Effluent quality was monitored at 162
      wastewater treatment works over 1 year, generating over 3,000 results for each of
      over 40 substances, including metals, trace organic substances and
      pharmaceuticals. It is demonstrated that the lognormal assumption is clearly
      justified for the great majority of substances in the spatial case-for annual
      average effluent concentrations across different treatment works. In the site
      specific, temporal case-for individual determinations of concentration at a
      single site over an annual period-lognormality is generally supported but not
      demonstrated so unequivocally for all site/substance combinations. The principal
      source of uncertainty was lack of sufficient numbers of observations reported to
      adequately low reporting limits. 

PMID- 24740390
TI  - Freshwater environmental quality parameters of man-made lakes of Serbia.
AB  - In this study, 28 lakes were selected from the freshwater resources of the
      network of man-made lakes throughout the Vojvodina Province and the central part
      of Serbia. Samples were analyzed for the physicochemicals indicators of the water
      and nutrients. Most of the values of the chemicals indicators and nutrients of
      the samples from the Vojvodina Province exceeded the Water Act and Regulations on
      the Monitoring of Water Quality introduced by the Government of the Republic of
      Serbia (MWQ) and/or the World Health Organization (WHO) drinking water standards.
      These samples may not be suitable for human consumption. The sample from Lake
      Meduvrsje, where the NH4 (+) concentration was 0.28 mg/L, and the sample from
      Ovcar Banja, where the total phosphorus (TP) content was 0.15 mg/L with a high
      total nitrogen (TN) content of 1.21 mg/L, are particularly noteworthy. These high
      concentrations exceeded the proposed guidelines for safe drinking water;
      therefore, water from these lakes should be used with care as harmful health
      effects may occur. The majority of the Serbian lakes are characterized by
      phosphorus-limited photosynthesis. 

PMID- 24740392
TI  - [Conservative treatment strategies for gonarthritis. New trends and established
      therapy concepts].
AB  - This article gives a current overview of non-operative procedures in cases of
      osteoarthritis of the knee, e.g. with special medications, local physiotherapy
      and gymnastic therapy including ergotherapy and aids for activities of daily
      living (ADL). 

PMID- 24740391
TI  - Mismatch negativity latency and cognitive function in schizophrenia.
AB  - BACKGROUND: The Mismatch Negativity (MMN) is an event-related potential (ERP)
      sensitive to early auditory deviance detection and has been shown to be reduced
      in schizophrenia patients. Moreover, MMN amplitude reduction to duration deviant
      tones was found to be related to functional outcomes particularly, to
      neuropsychological (working memory and verbal domains) and psychosocial measures.
      While MMN amplitude is thought to be correlated with deficits of early sensory
      processing, the functional significance of MMN latency remains unclear so far.
      The present study focused on the investigation of MMN in relation to
      neuropsychological function in schizophrenia. METHOD: Forty schizophrenia
      patients and 16 healthy controls underwent a passive oddball paradigm (2400
      binaural tones; 88% standards [1 kHz, 80 db, 80 ms], 11% frequency deviants [1.2
      kHz], 11% duration deviants [40 ms]) and a neuropsychological test-battery.
      Patients were assessed with regard to clinical symptoms. RESULTS: Compared to
      healthy controls schizophrenia patients showed diminished MMN amplitude and
      shorter MMN latency to both deviants as well as an impaired neuropsychological
      test performance. Severity of positive symptoms was related to decreased MMN
      amplitude to duration deviants. Furthermore, enhanced verbal memory performance
      was associated with prolonged MMN latency to frequency deviants in patients.
      CONCLUSION: The present study corroborates previous results of a diminished MMN
      amplitude and its association with positive symptoms in schizophrenia patients.
      Both, the findings of a shorter latency to duration and frequency deviants and
      the relationship of the latter with verbal memory in patients, emphasize the
      relevance of the temporal aspect of early auditory discrimination processing in
      schizophrenia.

PMID- 24740393
TI  - Effect of iodine excess on Th1, Th2, Th17, and Treg cell subpopulations in the
      thyroid of NOD.H-2h4 mice.
AB  - Iodine is an indispensable micronutrient for thyroid hormone synthesis and
      metabolism. Iodine excess may trigger and exacerbate autoimmune thyroiditis
      (AIT). The pathogenetic mechanism of iodine excess-induced AIT is partly regarded
      as T helper type 1 (Th1) cell and/or T helper type 17 (Th17) cell dominant
      autoimmune disease. It is still unknown whether other cluster of differentiation
      4+ T (CD4+T) cell subpopulations are involved. Therefore, we studied the profile
      of all the CD4+T cell subpopulations of the thyroid in iodine excess-induced
      nonobese diabetic-H2h4 (NOD.H-2h4) mice to explore the potential immunologic
      mechanism of iodine excess-induced AIT. A total of 40 healthy 8-week-old NOD.H
      2h4 mice were randomly allocated into the normal group (NG, n=20) and the test
      group (TG, n=20), which were fed with double-distilled water and 0.05% sodium
      iodine (NaI) for 8 weeks, respectively. Compared to the NG, in the TG, the
      incidence of AIT was significantly higher, the expressions of interleukin-17 (IL
      17), interleukin-23 (IL-23), interleukin-6 (IL-6), and transforming growth factor
      beta (TGF-beta) remarkably increased by immunohistochemistry, which were further
      verified by reverse transcription polymerase chain reaction (RT-PCR), while the
      protein and mRNA expressions of interleukin-4 (IL-4) and interferon-gamma (INF
      gamma) decreased markedly. In the AIT mice, the expressions of retinoic acid
      related orphan receptor gamma t (RORgammat), retinoic acid-related orphan
      receptor alpha (RORalpha), and signal transducer and activator of transcription 3
      (STAT3) were much higher, the expression of forkhead/winged helix transcription
      factor p3 (Foxp3) significantly lower by western blot, and the proportion of Th17
      cells by flow cytometry method (FCM) much larger compared to those of the NG
      group. In conclusion, Th17 cells may promote an inflammatory reaction in the
      development of iodine-excess-induced AIT, which is negatively regulated by Th1, T
      helper type 2 (Th2), and regulatory T (Treg) cells.

PMID- 24740394
TI  - Water-soluble ruthenium complexes bearing activity against protozoan parasites.
AB  - Parasitic illnesses are major causes of human disease and misery worldwide. Among
      them, both amebiasis and Chagas disease, caused by the protozoan parasites,
      Entamoeba histolytica and Trypanosoma cruzi, are responsible for thousands of
      annual deaths. The lack of safe and effective chemotherapy and/or the appearance
      of current drug resistance make the development of novel pharmacological tools
      for their treatment relevant. In this sense, within the framework of the
      medicinal inorganic chemistry, metal-based drugs appear to be a good alternative
      to find a pharmacological answer to parasitic diseases. In this work, novel
      ruthenium complexes [RuCl2(HL)(HPTA)2]Cl2 with HL=bioactive 5-nitrofuryl
      containing thiosemicarbazones and PTA=1,3,5-triaza-7-phosphaadamantane have been
      synthesized and fully characterized. PTA was included as co-ligand in order to
      modulate complexes aqueous solubility. In fact, obtained complexes were water
      soluble. Their activity against T. cruzi and E. histolytica was evaluated in
      vitro. [RuCl2(HL4)(HPTA)2]Cl2 complex, with HL4=N-phenyl-5-nitrofuryl
      thiosemicarbazone, was the most active compound against both parasites. In
      particular, it showed an excellent activity against E. histolytica (half maximal
      inhibitory concentration (IC50)=5.2 MUM), even higher than that of the reference
      drug metronidazole. In addition, this complex turns out to be selective for E.
      histolytica (selectivity index (SI)>38). The potential mechanism of antiparasitic
      action of the obtained ruthenium complexes could involve oxidative stress for
      both parasites. Additionally, complexes could interact with DNA as second
      potential target by an intercalative-like mode. Obtained results could be
      considered a contribution in the search for metal compounds that could be active
      against multiple parasites.

PMID- 24740395
TI  - Nitrite promotes the growth and decreases the lignin content of indica rice
      calli: a comprehensive transcriptome analysis of nitrite-responsive genes during
      in vitro culture of rice.
AB  - As both major macronutrients and signal molecules, nitrogen metabolites, such as
      nitrate and nitrite, play an important role in plant growth and development. In
      this study, the callus growth of indica rice cv. 9311 was significantly enhanced
      by nitrite, whereas the soluble protein content remained unchanged. The deep RNA
      sequencing technology (RNA-seq) showed that the transcriptional profiles of cv.
      9311 calli were significantly changed after adding nitrite to the nitrate-free
      medium, and these nitrite-responsive genes were involved in a wide range of plant
      processes, particularly in the secondary metabolite pathways. Interestingly, most
      of the genes involved in phenylpropanoid-related pathways were coordinately down
      regulated by nitrite, such as four cinnamoyl-CoA reductase, and these in turn
      resulted in the decrease of lignin content of indica calli. Furthermore, several
      candidate genes related to cell growth or stress responses were identified, such
      as genes coding for expansins, SMALL AUXIN UP RNA (SAUR) and HSP20s, and these
      suggested that nitrite could probably serve as a transcriptome signal to enhance
      the indica calli growth by regulation of various downstream genes expression.
      This study contributes to a better understanding of the function of nitrite
      during the process of plant tissue culture and could aid in the application of
      this technology to improved indica genetic transformation efficiency. 

PMID- 24740398
TI  - Elastosis perforans serpiginosa: a case of a penicillamine-induced degenerative
      dermatosis.

PMID- 24740396
TI  - The relationship between the structure of the tick-borne encephalitis virus
      strains and their pathogenic properties.
AB  - Tick-borne encephalitis virus (TBEV) is transmitted to vertebrates by taiga or
      forest ticks through bites, inducing disease of variable severity. The reasons
      underlying these differences in the severity of the disease are unknown. In order
      to identify genetic factors affecting the pathogenicity of virus strains, we have
      sequenced and compared the complete genomes of 34 Far-Eastern subtype (FE) TBEV
      strains isolated from patients with different disease severity (Primorye, the
      Russian Far East). We analyzed the complete genomes of 11 human pathogenic
      strains isolated from the brains of dead patients with the encephalitic form of
      the disease (Efd), 4 strains from the blood of patients with the febrile form of
      TBE (Ffd), and 19 strains from patients with the subclinical form of TBE (Sfd).
      On the phylogenetic tree, pathogenic Efd strains formed two clusters containing
      the prototype strains, Senzhang and Sofjin, respectively. Sfd strains formed a
      third separate cluster, including the Oshima strain. The strains that caused the
      febrile form of the disease did not form a separate cluster. In the viral
      proteins, we found 198 positions with at least one amino acid residue
      substitution, of which only 17 amino acid residue substitutions were correlated
      with the variable pathogenicity of these strains in humans and they authentically
      differed between the groups. We considered the role of each amino acid
      substitution and assumed that the deletion of 111 amino acids in the capsid
      protein in combination with the amino acid substitutions R16K and S45F in the NS3
      protease may affect the budding process of viral particles. These changes may be
      the major reason for the diminished pathogenicity of TBEV strains. We recommend
      Sfd strains for testing as attenuation vaccine candidates. 

PMID- 24740399
TI  - Evaluation of the distribution and impacts of parasites, pathogens, and
      pesticides on honey bee (Apis mellifera) populations in East Africa.
AB  - In East Africa, honey bees (Apis mellifera) provide critical pollination services
      and income for small-holder farmers and rural families. While honey bee
      populations in North America and Europe are in decline, little is known about the
      status of honey bee populations in Africa. We initiated a nationwide survey
      encompassing 24 locations across Kenya in 2010 to evaluate the numbers and sizes
      of honey bee colonies, assess the presence of parasites (Varroa mites and Nosema
      microsporidia) and viruses, identify and quantify pesticide contaminants in
      hives, and assay for levels of hygienic behavior. Varroa mites were present
      throughout Kenya, except in the remote north. Levels of Varroa were positively
      correlated with elevation, suggesting that environmental factors may play a role
      in honey bee host-parasite interactions. Levels of Varroa were negatively
      correlated with levels of hygienic behavior: however, while Varroa infestation
      dramatically reduces honey bee colony survival in the US and Europe, in Kenya
      Varroa presence alone does not appear to impact colony size. Nosema apis was
      found at three sites along the coast and one interior site. Only a small number
      of pesticides at low concentrations were found. Of the seven common US/European
      honey bee viruses, only three were identified but, like Varroa, were absent from
      northern Kenya. The number of viruses present was positively correlated with
      Varroa levels, but was not correlated with colony size or hygienic behavior. Our
      results suggest that Varroa, the three viruses, and Nosema have been relatively
      recently introduced into Kenya, but these factors do not yet appear to be
      impacting Kenyan bee populations. Thus chemical control for Varroa and Nosema are
      not necessary for Kenyan bees at this time. This study provides baseline data for
      future analyses of the possible mechanisms underlying resistance to and the long
      term impacts of these factors on African bee populations. 

PMID- 24740401
TI  - Cross-sectional analysis of obesity and serum analytes in males identifies sRAGE
      as a novel biomarker inversely associated with diverticulosis.
AB  - Diverticulosis can lead to diverticulitis, a colon condition involving
      inflammation and other complications. Diverticulosis can result from biological,
      behavioral, or genetic causes. However, the etiology of diverticulosis is
      unknown. Although diet is associated with diverticulosis, recent studies suggest
      other factors influence risk. We sought to identify anthropometric or serum
      markers that were associated with the presence of diverticulosis. To determine
      these associations, 126 asymptomatic men (48-65 yr) were recruited at the time of
      preventative screening colonoscopy. Anthropometric measures were taken, and blood
      was collected for serum protein analysis. Data were analyzed by logistic
      regression and factor analysis. Obese individuals (BMI >30) were 7.8 (CI: 2.3
      26.3) times more likely than normal weight (BMI <25) individuals to have
      diverticulosis. The relationship was similar for waist circumference. Individuals
      with a waist circumference >45 inches were 8.1 (CI: 2.8-23.8) times more likely
      to have diverticulosis than those with a waist circumference <38 inches. Leptin
      was also positively associated with diverticulosis (OR = 5.5, CI: 2.0-14.7). Both
      low molecular weight adiponectin (LMW, OR = 0.50; CI: 0.3-0.8) and the soluble
      receptor for advanced glycation end products (sRAGE, OR = 0.4, CI: 0.3-0.7) were
      inversely related to the presence of diverticulosis. sRAGE levels were not
      correlated with leptin or C-peptide concentrations. The pattern of high BMI,
      waist circumference, leptin and C-peptide increased the odds of diverticulosis
      while the pattern of high levels of sRAGE and LMW adiponectin decreased the odds
      of diverticulosis. Associations between diverticulosis and anthropometric or
      serum markers may elucidate the origins of diverticulosis and may enable
      physicians to identify individuals at risk for diverticulitis.

PMID- 24740400
TI  - Ursolic acid inhibits leucine-stimulated mTORC1 signaling by suppressing mTOR
      localization to lysosome.
AB  - Ursolic acid (UA), a pentacyclic triterpenoid widely found in medicinal herbs and
      fruits, has been reported to possess a wide range of beneficial properties
      including anti-hyperglycemia, anti-obesity, and anti-cancer. However, the
      molecular mechanisms underlying the action of UA remain largely unknown. Here we
      show that UA inhibits leucine-induced activation of the mechanistic target of
      rapamycin complex 1 (mTORC1) signaling pathway in C2C12 myotubes. The UA-mediated
      inhibition of mTORC1 is independent of Akt, tuberous sclerosis complex 1/2
      (TSC1/2), and Ras homolog enriched in brain (Rheb), suggesting that UA negatively
      regulates mTORC1 signaling by targeting at a site downstream of these mTOR
      regulators. UA treatment had no effect on the interaction between mTOR and its
      activator Raptor or inhibitor Deptor, but suppressed the binding of RagB to
      Raptor and inhibited leucine-induced mTOR lysosomal localization. Taken together,
      our study identifies UA as a direct negative regulator of the mTORC1 signaling
      pathway and suggests a novel mechanism by which UA exerts its beneficial
      function. 

PMID- 24740402
TI  - Diagnosis of pancreatic cancer by contrast-harmonic endoscopic ultrasound (EUS):
      complementary and not competitive with EUS-guided fine-needle aspiration.

PMID- 24740403
TI  - Successful treatment of Barrett's esophagus with radiofrequency ablation in a
      patient with severe reflux esophagitis following fundoplication.

PMID- 24740404
TI  - Reply to Oh et al.

PMID- 24740406
TI  - Epigenetics, the holy grail in the pathogenesis of systemic sclerosis.
AB  - The objective of this review is to present evidence that supports the central
      role of epigenetic regulation in the pathogenesis of SSc. SSc is a complex
      autoimmune disease characterized by immune activation, fibrosis of the skin and
      internal organs and obliterative vasculopathy affecting predominantly the
      microvessels. Remarkable progress has been made in the past few years emphasizing
      the importance of epigenetic modifications in the pathogenesis of many disorders,
      including SSc. Current evidence demonstrates alterations in DNA methylation,
      histone code modifications and changes in microRNA (miRNA) expression levels in
      SSc cells. Recent reports have described the differential expression of numerous
      regulatory miRNAs in SSc, mainly in SSc fibroblasts, a number of which are
      important in TGF-beta pathways and downstream signalling cascades. While studies
      to date have revealed the significant role of epigenetic modifications in the
      pathogenesis of SSc, the causal nature of epigenetic alterations in SSc
      pathogenesis remains elusive. Additional longitudinal and comprehensive
      epigenetic studies designed to evaluate the effect of environmental epigenetic
      factors on disease pathogenesis are needed. 

PMID- 24740405
TI  - Activity-dependent dendritic spine shrinkage and growth involve downregulation of
      cofilin via distinct mechanisms.
AB  - A current model posits that cofilin-dependent actin severing negatively impacts
      dendritic spine volume. Studies suggested that increased cofilin activity
      underlies activity-dependent spine shrinkage, and that reduced cofilin activity
      induces activity-dependent spine growth. We suggest instead that both types of
      structural plasticity correlate with decreased cofilin activity. However, the
      mechanism of inhibition determines the outcome for spine morphology. RNAi in rat
      hippocampal cultures demonstrates that cofilin is essential for normal spine
      maintenance. Cofilin-F-actin binding and filament barbed-end production decrease
      during the early phase of activity-dependent spine shrinkage; cofilin
      concentration also decreases. Inhibition of the cathepsin B/L family of proteases
      prevents both cofilin loss and spine shrinkage. Conversely, during activity
      dependent spine growth, LIM kinase stimulates cofilin phosphorylation, which
      activates phospholipase D-1 to promote actin polymerization. These results
      implicate novel molecular mechanisms and prompt a revision of the current model
      for how cofilin functions in activity-dependent structural plasticity. 

PMID- 24740407
TI  - Contamination of organochlorine pesticides in water and sediments from a
      waterbird-inhabited lake, East Central China.
AB  - Seventeen organochlorine pesticides (OCPs) were investigated in the water and
      sediments from a waterbird-inhabited lake (Yangchaihu Lake) to evaluate their
      current pollution levels and potential risks. The concentrations of total OCPs in
      water and sediments were 10.12-59.75 ng/l and 4.25-27.35 ng/g dry weight,
      respectively. Hexachlorocyclohexanes (HCHs) and dichlorodiphenyltrichloroethanes
      (DDTs) were the most abundant OCPs, while HCB and cyclodiene pesticides were
      detected with low levels. Levels of ?OCPs (sum of 17 OCPs) at sites highly
      influenced by waterbirds were significantly higher than the sites with no
      significant waterbird populations (one-way ANOVA, P<0.05), suggesting that bird
      activities were one reason for concentration distribution of these pollutants.
      Compositional and source analyses of OCPs in water and sediments indicated that
      there might be fresh introduction of lindane and heptachlor. The partitions of
      most OCPs were not in equilibrium between water and sediments. The results of an
      ecological risk assessment showed that residue levels of DDTs in the studied area
      might pose adverse effects on ecosystems.

PMID- 24740408
TI  - A styletted tracheal tube with a posterior-facing bevel reduces epistaxis during
      nasal intubation: a randomized trial.
AB  - PURPOSE: Epistaxis is a common complication of nasal intubation. Ease of
      insertion of the tracheal tube may be influenced by bevel orientation and tip
      bending. We examined ease of insertion and epistaxis with two tubes with
      different orientations and with or without a stylet to modify tip bending.
      METHODS: Two hundred patients scheduled to undergo oral or maxillofacial surgery
      were randomized into four groups according to method of nasal intubation used
      after induction of anesthesia. In one group, a Portex((r)) tracheal tube was
      inserted with bevel facing left (Portex Group). In the second group, a Parker
      Flex-Tip((r)) tube (Parker Group) was inserted with the bevel facing posteriorly,
      and in the last two groups, a stylet bent at 60 degrees  anteriorly was used with
      the Portex tube (Stylet-Portex Group) or Parker tube (Stylet-Parker Group). When
      the tube advanced without resistance, insertion was defined as "smooth", and when
      resistance was encountered, insertion was defined as "impinged". Severity of
      epistaxis was evaluated as none, mild, moderate, or severe. RESULTS: Smooth
      insertion was observed in 60% of patients in the Portex Group; 80% in the Parker
      Group; 100% in the Stylet-Portex Group; and 100% in the Stylet-Parker Group.
      Epistaxis was found in 50%, 24%, 20%, and 4% of patients, respectively. The
      styletted tip (difference: 30%; 95% confidence interval [CI]: 20.3 to 38.5; P <
      0.0001) was found to improve ease of insertion. Both the posterior-facing bevel
      (difference: 21%; 95% CI: 9.0 to 32.1; P = 0.0005) and stylet (difference: 25%;
      95% CI: 13.1 to 35.9; P < 0.0001) contributed significantly to absence of
      epistaxis. CONCLUSIONS: Using a styletted tracheal tube with a posterior-facing
      bevel improves ease of insertion through the nasopharynx and decreases the
      severity of epistaxis during nasal intubation. CLINICAL TRIAL REGISTRATION
      NUMBER: UMIN Clinical Trials Registry (UMIN-CTR), UMIN000011327.

PMID- 24740409
TI  - Can metal ion complexation compete with the self-assembly processes of
      calix[4]arene amine derivatives?
AB  - Self-assembly can occur spontaneously through aryl-aryl pi-stacking in solution
      for calix[4]arenes derivatised at both the upper and lower rims with pendant
      aromatic rings, including pyridine rings. It was hoped that metal ion
      complexation would help to control the level of self-assembly occurring in
      solution, by disrupting these interactions. Metal ion titration studies were
      carried out on 3 with various zinc salts, but it was found that even with 1 : 4
      ligand to metal ratio, the self-assembly process still dominated. Furthermore, in
      an effort to prevent the self-assembly process, the lower rim was completely
      substituted, but metal complexation reactions with these fully substituted
      calix[4]arenes still showed that the self-assembly process dominated. 

PMID- 24740410
TI  - RAGE/NF-kappaB pathway mediates lipopolysaccharide-induced inflammation in
      alveolar type I epithelial cells isolated from neonate rats.
AB  - Alveolar type I epithelial cells (AECIs) play an important role in the
      pathogenesis of acute lung injury. The receptor for advanced glycation end
      products (RAGEs) is expressed at a high basal level in AECIs, and its soluble
      isoform is suggested as a marker of AECI injury. However, the molecular mechanism
      by which RAGE mediates inflammatory injury in AECIs remains elusive. In this
      study, we established lipopolysaccharide (LPS)-induced inflammation in AECIs
      isolated from neonate rats as the experimental model and investigated the role of
      RAGE/NF-kappaB signaling in mediating inflammatory response in AECIs. We found
      that LPS increased RAGE expression and the secretion of tumor necrosis factor
      alpha (TNF-alpha) and interleukin-1 beta (IL-1beta) in AECIs in a dose-dependent
      manner. Knockdown of RAGE significantly decreased TNF-alpha and IL-1beta levels
      in conditioned medium of AECIs. Electrophoretic mobility shift assay (EMSA)
      showed that NF-kappaB activation was increased in AECIs treated by LPS. However,
      knockdown of RAGE inhibited both basic and LPS-induced NF-kappaB activity in
      AECIs. Finally, NF-kappaB inhibitor pyrrolidine dithiocarbamate (PDTC)
      significantly reduced LPS-induced upregulation of RAGE expression at both protein
      and messenger RNA (mRNA) levels in AECIs. Our results suggest that RAGE mediates
      inflammatory response in AECIs via activating NF-kappaB, and RAGE/NF-kappaB
      pathway presents potential target for the prevention and therapy of acute lung
      injury. 

PMID- 24740411
TI  - Whole CMV proteome pattern recognition analysis after HSCT identifies unique
      epitope targets associated with the CMV status.
AB  - Cytomegalovirus (CMV) infection represents a vital complication after
      Hematopoietic Stem Cell Transplantation (HSCT). We screened the entire CMV
      proteome to visualize the humoral target epitope-focus profile in serum after
      HSCT. IgG profiling from four patient groups (donor and/or recipient +/- for CMV)
      was performed at 6, 12 and 24 months after HSCT using microarray slides
      containing 17174 of 15mer-peptides overlapping by 4 aa covering 214 proteins from
      CMV. Data were analyzed using maSigPro, PAM and the 'exclusive recognition
      analysis (ERA)' to identify unique CMV epitope responses for each patient group.
      The 'exclusive recognition analysis' of serum epitope patterns segregated best 12
      months after HSCT for the D+/R+ group (versus D-/R-). Epitopes were derived from
      UL123 (IE1), UL99 (pp28), UL32 (pp150), this changed at 24 months to 2 strongly
      recognized peptides provided from UL123 and UL100. Strongly (IgG) recognized CMV
      targets elicited also robust cytokine production in T-cells from patients after
      HSCT defined by intracellular cytokine staining (IL-2, TNF, IFN and IL-17). High
      content peptide microarrays allow epitope profiling of entire viral proteomes;
      this approach can be useful to map relevant targets for diagnostics and therapy
      in patients with well defined clinical endpoints. Peptide microarray analysis
      visualizes the breadth of B-cell immune reconstitution after HSCT and provides a
      useful tool to gauge immune reconstitution. 

PMID- 24740412
TI  - Decomposition odour profiling in the air and soil surrounding vertebrate carrion.
AB  - Chemical profiling of decomposition odour is conducted in the environmental
      sciences to detect malodourous target sources in air, water or soil. More
      recently decomposition odour profiling has been employed in the forensic sciences
      to generate a profile of the volatile organic compounds (VOCs) produced by
      decomposed remains. The chemical profile of decomposition odour is still being
      debated with variations in the VOC profile attributed to the sample collection
      technique, method of chemical analysis, and environment in which decomposition
      occurred. To date, little consideration has been given to the partitioning of
      odour between different matrices and the impact this has on developing an
      accurate VOC profile. The purpose of this research was to investigate the
      decomposition odour profile surrounding vertebrate carrion to determine how VOCs
      partition between soil and air. Four pig carcasses (Sus scrofa domesticus L.)
      were placed on a soil surface to decompose naturally and their odour profile
      monitored over a period of two months. Corresponding control sites were also
      monitored to determine the VOC profile of the surrounding environment. Samples
      were collected from the soil below and the air (headspace) above the decomposed
      remains using sorbent tubes and analysed using gas chromatography-mass
      spectrometry. A total of 249 compounds were identified but only 58 compounds were
      common to both air and soil samples. This study has demonstrated that soil and
      air samples produce distinct subsets of VOCs that contribute to the overall
      decomposition odour. Sample collection from only one matrix will reduce the
      likelihood of detecting the complete spectrum of VOCs, which further confounds
      the issue of determining a complete and accurate decomposition odour profile.
      Confirmation of this profile will enhance the performance of cadaver-detection
      dogs that are tasked with detecting decomposition odour in both soil and air to
      locate victim remains. 

PMID- 24740413
TI  - A mutant of uracil DNA glycosylase that distinguishes between cytosine and 5
      methylcytosine.
AB  - We demonstrate that a mutant of uracil DNA glycosylase (N123D:L191A)
      distinguishes between cytosine and methylcytosine. Uracil DNA glycosylase (UDG)
      efficiently removes uracil from DNA in a reaction in which the base is flipped
      into the enzyme's active site. Uracil is selected over cytosine by a pattern of
      specific hydrogen bonds, and thymine is excluded by steric clash of its 5-methyl
      group with Y66. The N123D mutation generates an enzyme that excises cytosine.
      This N123D:L191A mutant excises C when it is mispaired with A or opposite an
      abasic site, but not when it is paired with G. In contrast no cleavage is
      observed with any substrates that contain 5-methylcytosine. This enzyme may offer
      a new approach for discriminating between cytosine and 5-methylcytosine. 

PMID- 24740414
TI  - Retraction. Up-regulation of pVHL along with down-regulation of HIF-1alpha by
      NDRG2 expression attenuates proliferation and invasion in renal cancer cells.

PMID- 24740415
TI  - Exosomes from drug-resistant breast cancer cells transmit chemoresistance by a
      horizontal transfer of microRNAs.
AB  - Adriamycin and docetaxel are two agents commonly used in treatment of breast
      cancer, but their efficacy is often limited by the emergence of chemoresistance.
      Recent studies indicate that exosomes act as vehicles for exchange of genetic
      cargo between heterogeneous populations of tumor cells, engendering a transmitted
      drug resistance for cancer development and progression. However, the specific
      contribution of breast cancer-derived exosomes is poorly understood. Here we
      reinforced other's report that human breast cancer cell line MCF-7/S could
      acquire increased survival potential from its resistant variants MCF-7/Adr and
      MCF-7/Doc. Additionally, exosomes of the latter, A/exo and D/exo, significantly
      modulated the cell cycle distribution and drug-induced apoptosis with respect to
      S/exo. Exosomes pre-treated with RNase were unable to regulate cell cycle and
      apoptosis resistance, suggesting an RNA-dependent manner. Microarray and
      polymerase chain reaction for the miRNA expression profiles of A/exo, D/exo, and
      S/exo demonstrated that they loaded selective miRNA patterns. Following A/exo and
      D/exo transfer to recipient MCF-7/S, the same miRNAs were significantly increased
      in acquired cells. Target gene prediction and pathway analysis showed the
      involvement of miR-100, miR-222, and miR-30a in pathways implicated in cancer
      pathogenesis, membrane vesiculation and therapy failure. Furthermore, D/exo co
      culture assays and miRNA mimics transfection experiments indicated that miR-222
      rich D/exo could alter target gene expression in MCF-7/S. Our results suggest
      that drug-resistant breast cancer cells may spread resistance capacity to
      sensitive ones by releasing exosomes and that such effects could be partly
      attributed to the intercellular transfer of specific miRNAs. 

PMID- 24740416
TI  - Gel formation in protein amyloid aggregation: a physical mechanism for
      cytotoxicity.
AB  - Amyloid fibers are associated with disease but have little chemical reactivity.
      We investigated the formation and structure of amyloids to identify potential
      mechanisms for their pathogenic effects. We incubated lysozyme 20 mg/ml at 55C
      and pH 2.5 in a glycine-HCl buffer and prepared slides on mica substrates for
      examination by atomic force microscopy. Structures observed early in the
      aggregation process included monomers, small colloidal aggregates, and amyloid
      fibers. Amyloid fibers were observed to further self-assemble by two mechanisms.
      Two or more fibers may merge together laterally to form a single fiber bundle,
      usually in the form of a helix. Alternatively, fibers may become bound at points
      where they cross, ultimately forming an apparently irreversible macromolecular
      network. As the fibers assemble into a continuous network, the colloidal
      suspension undergoes a transition from a Newtonian fluid into a viscoelastic gel.
      Addition of salt did not affect fiber formation but inhibits transition of fibers
      from linear to helical conformation, and accelerates gel formation. Based on our
      observations, we considered the effects of gel formation on biological transport.
      Analysis of network geometry indicates that amyloid gels will have negligible
      effects on diffusion of small molecules, but they prevent movement of colloidal
      sized structures. Consequently gel formation within neurons could completely
      block movement of transport vesicles in neuronal processes. Forced convection of
      extracellular fluid is essential for the transport of nutrients and metabolic
      wastes in the brain. Amyloid gel in the extracellular space can essentially halt
      this convection because of its low permeability. These effects may provide a
      physical mechanism for the cytotoxicity of chemically inactive amyloid fibers in
      neurodegenerative disease. 

PMID- 24740418
TI  - Allosteric control of a DNA-hydrolyzing deoxyribozyme with short oligonucleotides
      and its application in DNA logic gates.
AB  - Allosteric control of deoxyribozymes is useful for a broad range of practical
      applications, such as nucleic acid sensing and DNA-computing. We found that the
      catalytic activity of a DNA-hydrolyzing deoxyribozyme could be allosterically
      regulated by adding short oligonucleotides. We used this technique to construct
      deoxyribozyme-based logic gates. 

PMID- 24740417
TI  - Patients with tuberculosis disease have Mycobacterium tuberculosis-specific CD8 T
      cells with a pro-apoptotic phenotype and impaired proliferative capacity, which
      is not restored following treatment.
AB  - CD8 T cells play a critical role in control of chronic viral infections; however,
      the role of these cells in containing persistent bacterial infections, such as
      those caused by Mycobacterium tuberculosis (Mtb), is less clear. We assessed the
      phenotype and functional capacity of CD8 T cells specific for the immunodominant
      Mtb antigens CFP-10 and ESAT-6, in patients with pulmonary tuberculosis (TB)
      disease, before and after treatment, and in healthy persons with latent Mtb
      infection (LTBI). In patients with TB disease, CFP-10/ESAT-6-specific IFN-gamma+
      CD8 T cells had an activated, pro-apoptotic phenotype, with lower Bcl-2 and CD127
      expression, and higher Ki67, CD57, and CD95 expression, than in LTBI. When CFP
      10/ESAT-6-specific IFN-gamma+ CD8 T cells were detectable, expression of distinct
      combinations of these markers was highly sensitive and specific for
      differentiating TB disease from LTBI. Successful treatment of disease resulted in
      changes of these markers, but not in restoration of CFP-10/ESAT-6-specific CD8 or
      CD4 memory T cell proliferative capacity. These data suggest that high
      mycobacterial load in active TB disease is associated with activated, short-lived
      CFP-10/ESAT-6-specific CD8 T cells with impaired functional capacity that is not
      restored following treatment. By contrast, LTBI is associated with preservation
      of long-lived CFP-10/ESAT-6-specific memory CD8 T cells that maintain high Bcl-2
      expression and which may readily proliferate. 

PMID- 24740419
TI  - Long wavelength absorbing carbostyrils as test cases for different TDDFT
      procedures and solvent models.
AB  - The vertical excitation energies of 3,4-dicyano-6-methoxy and 3,4-dicyano-6,7
      dimethoxy carbostyril have been computed with different approximations for the
      time-dependent density functional theory (TD-DFT) procedure and with different
      implementations of the continuum solvation model COSMO. Different DFT functionals
      were tested in TD-DFT and Tamm-Dancoff approximations (TDA) for the excitation
      energies in the gas phase. TDA-B3LYP showed the best agreement with the
      experimental data. Then TDA-B3LYP computations were performed combined with the
      COSMO model of solvation comparing a linear response (LR) and a post
      configuration interaction (CI) implementation of the fast solvent reorganization.
      The post-CI solvent model overestimates the pi->pi* transitions and strongly
      underestimates the n->pi* transition. The TDA approximation in combination with
      the linear response implementation of the COSMO solvation model perfectly
      computes the experimental results. TDA-LR is the most reliable method for the
      computation of the vertical excitation energies in a solvent. Comparison with
      explicit solvent calculations shows there is only a minor effect on the energies
      of the electronic interaction of the solute with the solvent. 

PMID- 24740420
TI  - Quantitative trait loci (QTL) study identifies novel genomic regions associated
      to Chiari-like malformation in Griffon Bruxellois dogs.
AB  - Chiari-like malformation (CM) is a developmental abnormality of the
      craniocervical junction that is common in the Griffon Bruxellois (GB) breed with
      an estimated prevalence of 65%. This disease is characterized by overcrowding of
      the neural parenchyma at the craniocervical junction and disturbance of
      cerebrospinal fluid (CSF) flow. The most common clinical sign is pain either as a
      direct consequence of CM or neuropathic pain as a consequence of secondary
      syringomyelia. The etiology of CM remains unknown but genetic factors play an
      important role. To investigate the genetic complexity of the disease, a
      quantitative trait locus (QTL) approach was adopted. A total of 14 quantitative
      skull and atlas measurements were taken and were tested for association to CM.
      Six traits were found to be associated to CM and were subjected to a whole-genome
      association study using the Illumina canine high density bead chip in 74 GB dogs
      (50 affected and 24 controls). Linear and mixed regression analyses identified
      associated single nucleotide polymorphisms (SNPs) on 5 Canis Familiaris Autosomes
      (CFAs): CFA2, CFA9, CFA12, CFA14 and CFA24. A reconstructed haplotype of 0.53 Mb
      on CFA2 strongly associated to the height of the cranial fossa (diameter F) and
      an haplotype of 2.5 Mb on CFA14 associated to both the height of the rostral part
      of the caudal cranial fossa (AE) and the height of the brain (FG) were
      significantly associated to CM after 10 000 permutations strengthening their
      candidacy for this disease (P = 0.0421, P = 0.0094 respectively). The CFA2 QTL
      harbours the Sall-1 gene which is an excellent candidate since its orthologue in
      humans is mutated in Townes-Brocks syndrome which has previously been associated
      to Chiari malformation I. Our study demonstrates the implication of multiple
      traits in the etiology of CM and has successfully identified two new QTL
      associated to CM and a potential candidate gene. 

PMID- 24740423
TI  - Rayleigh wave propagation in nematic elastomers.
AB  - In this paper, Rayleigh wave propagation in nematic elastomers (NEs) is
      investigated. Characteristic equations for Rayleigh waves in the NEs are derived
      based on the viscoelastic theory of nematic elastomers in the low-frequency
      (hydrodynamic) limit. The dispersion and attenuation properties of the Rayleigh
      waves in the NEs are analyzed numerically. By considering the effects of the
      director, the rubber relaxation time and the dynamic soft elasticity of the NEs
      on the propagation characteristics of the Rayleigh waves are investigated.
      Results show that unlike Rayleigh waves in pure viscous materials, the Rayleigh
      wave displays obvious frequency dependence due to the dynamic soft elasticity of
      the NEs. There exists a critical transition frequency above which the Rayleigh
      wave velocity is gradually increased to a stable value, and at this frequency the
      Rayleigh wave velocity is temperature independent. The transition critical
      frequency where liquid behavior changes to rubber performance is director
      rotation time dependent, whilst the rubber relaxation time has less of an effect
      on its value. Although the particle trace is still elliptically polarized, the
      direction of the major axis is frequency and depth dependent. Clarification of
      these particular properties of Rayleigh waves is helpful for the further acoustic
      application of Rayleigh waves in NEs. 

PMID- 24740421
TI  - Regulation of insulin degrading enzyme activity by obesity-associated factors and
      pioglitazone in liver of diet-induced obese mice.
AB  - Insulin degrading enzyme (IDE) is a potential drug target in the treatment of
      type 2 diabetes (T2D). IDE controls circulating insulin through a degradation
      dependent clearance mechanism in multiple tissues. However, there is not
      sufficient information about IDE regulation in obesity. In this study, we test
      obesity-associated factors and pioglitazone in the regulation of IDE in diet
      induced obese (DIO) C57BL/6 mice. The enzyme activity and protein level of IDE
      were increased in the liver of DIO mice. Pioglitazone (10 mg/kg/day)
      administration for 2 months significantly enhanced the enzyme activity (75%),
      protein (180%) and mRNA (100%) of IDE in DIO mice. The pioglitazone-induced
      changes were coupled with 50% reduction in fasting insulin and 20% reduction in
      fasting blood glucose. The mechanism of IDE regulation in liver was investigated
      in the mouse hepatoma cell line (Hepa 1c1c7 cells), in which pioglitazone (5 uM)
      increased IDE protein and mRNA in a time-dependent manner in an 8 h study. Free
      fatty acid (palmitate 300 uM) induced IDE protein, but reduced the mRNA. Glucagon
      induced, and TNF-alpha decreased IDE protein. Insulin did not exhibit any
      activity in the same condition. In summary, pioglitazone, FFA and glucagon
      directly increased, but TNF-alpha decreased the IDE activity in hepatocytes. The
      results suggest that IDE activity is regulated in liver by multiple factors in
      obesity and pioglitazone may induce IDE activity in the control of T2D. 

PMID- 24740424
TI  - Influence analysis in quantitative trait loci detection.
AB  - This paper presents systematic methods for the detection of influential
      individuals that affect the log odds (LOD) score curve. We derive general
      formulas of influence functions for profile likelihoods and introduce them into
      two standard quantitative trait locus detection methods-the interval mapping
      method and single marker analysis. Besides influence analysis on specific LOD
      scores, we also develop influence analysis methods on the shape of the LOD score
      curves. A simulation-based method is proposed to assess the significance of the
      influence of the individuals. These methods are shown useful in the influence
      analysis of a real dataset of an experimental population from an F2 mouse cross.
      By receiver operating characteristic analysis, we confirm that the proposed
      methods show better performance than existing diagnostics. 

PMID- 24740425
TI  - Bilateral upper extremity erythematous plaques.

PMID- 24740426
TI  - Association of adiponectin gene (ADIPOQ) rs2241766 polymorphism with obesity in
      adults: a meta-analysis.
AB  - BACKGROUND: Adiponectin plays an important role in regulating glucose levels and
      fatty acid oxidation. Multiple studies have assessed the association between
      rs2241766 polymorphism in the adiponectin (ADIPOQ) gene and obesity
      susceptibility. However, the results are inconsistent and inconclusive. The aim
      of this meta-analysis was to investigate this association in adults. METHOD:
      Several electronic databases were searched for relevant literature published up
      to November 2013. Statistical analyses were performed using software Review
      Manager (Version 5.02) and STATA (Version 10.0). The pooled odds ratios (ORs) and
      95% confidence intervals (CIs) were calculated with a random-effects model or a
      fixed-effect model depending on heterogeneity among studies. Q tests and Egger's
      tests were performed to assess heterogeneity and publication bias. Sensitivity
      analysis was conducted to confirm the reliability and stability of the meta
      analysis. RESULTS: A total of 2,819 obese and 3,024 controls in 18 case-control
      studies were included in the meta-analysis. The results indicated that compared
      with TT genotype, the ADIPOQ-rs2241766 GG genotype was associated with an
      increased risk for obesity (OR = 1.39, 95% CI: 1.11-1.73, P for heterogeneity =
      0.520, I2 = 0%) in overall studies. Whereas, GT genotype was associated with a
      borderland increased risk for obesity (OR = 1.13, 95% CI: 0.94-1.36, P for
      heterogeneity = 0.006, I2 = 51%). The susceptibility of obesity was increased
      based on genotypes of TT<GT<GG (P for trend = 0.011). Subgroup analysis of
      different regions revealed that the ADIPOQ-rs2241766 GG genotype increased
      obesity risk in the Chinese studies (OR = 1.54, 95% CI: 1.19-2.00) but not in the
      non-Chinese studies (OR = 1.02, 95% CI: 0.66-1.58). Similar results were observed
      in allelic, recessive, and dominant genetic models. There was no significant
      evidence of publication bias in the overall, Chinese, and non-Chinese studies (P
      = 0.426, P = 0.935, and P = 0.390, respectively). CONCLUSION: The results of this
      meta-analysis suggest that the ADIPOQ-rs2241766 G/T polymorphism might be
      associated with obesity in Chinese studies but not in non-Chinese studies in
      adults. Better-designed studies that consider confounding factors and assess
      larger sample sizes with a focus on ADIPOQ-rs2241766G/T polymorphisms and obesity
      are required in the future.

PMID- 24740427
TI  - Efficacy of N-acetyl cysteine in traumatic brain injury.
AB  - In this study, using two different injury models in two different species, we
      found that early post-injury treatment with N-Acetyl Cysteine (NAC) reversed the
      behavioral deficits associated with the TBI. These data suggest generalization of
      a protocol similar to our recent clinical trial with NAC in blast-induced mTBI in
      a battlefield setting, to mild concussion from blunt trauma. This study used both
      weight drop in mice and fluid percussion injury in rats. These were chosen to
      simulate either mild or moderate traumatic brain injury (TBI). For mice, we used
      novel object recognition and the Y maze. For rats, we used the Morris water maze.
      NAC was administered beginning 30-60 minutes after injury. Behavioral deficits
      due to injury in both species were significantly reversed by NAC treatment. We
      thus conclude NAC produces significant behavioral recovery after injury. Future
      preclinical studies are needed to define the mechanism of action, perhaps leading
      to more effective therapies in man.

PMID- 24740428
TI  - Central projections of gustatory receptor neurons in the medial and the lateral
      sensilla styloconica of Helicoverpa armigera larvae.
AB  - Food selection behavior of lepidopteran larvae is predominantly governed by the
      activation of taste neurons present in two sensilla styloconica located on the
      galea of the maxilla. In this study, we present the ultrastructure of the
      sensilla styloconica and the central projection pattern of their associated
      receptor neurons in larvae of the heliothine moth, Helicoverpa armigera. By means
      of light microscopy and scanning electron microscopy, the previous findings of
      two morphologically fairly similar sensilla comprising a socketed conic tip
      inserted into a large peg were confirmed. However, the peg size of the medial
      sensillum was found to be significantly bigger than that of the lateral
      sensillum. The sensory neurons derived from each sensillum styloconicum were
      mapped separately using anterograde staining experiments combined with confocal
      laser-scanning microscopy. For determining the afferents' target regions relative
      to each other, we reconstructed the labeled axons and placed them into a common
      reference framework. The sensory axons from both sensilla projected via the
      ipsilateral maxillary nerve to the suboesophageal ganglion and further through
      the ipsilateral circumoesophageal connective to the brain. In the suboesophageal
      ganglion, the sensory projections targeted two areas of the ipsilateral maxillary
      neuropil, one located in the ventrolateral neuromere and the other adjacent to
      the neuromere midline. In the brain, the axon terminals targeted the dorso
      anterior area of the ipsilateral tritocerebrum. As confirmed by the three
      dimensional reconstructions, the target regions of the neural projections
      originating from each of the two sensilla styloconica were identical. 

PMID- 24740431
TI  - The effects of listener training on the emergence of categorization and speaker
      behavior in children with autism.
AB  - We evaluated the effects of listener training on the emergence of categorization
      and speaker behavior (i.e., tacts) using a nonconcurrent multiple baseline
      design. Four children with autism learned to select pictures given their dictated
      category names. We assessed whether they could match and tact pictures by
      category. After training, 3 participants tacted and categorized all pictures, and
      1 participant failed both tests. After tact training, this participant
      categorized. These results suggest that listener training may be an efficient way
      to produce speaker behavior and categorization in children who have been
      diagnosed with autism. 

PMID- 24740430
TI  - PACAP protects against inflammatory-mediated toxicity in dopaminergic SH-SY5Y
      cells: implication for Parkinson's disease.
AB  - There has been a growing recognition of the role of neuroinflammation caused by
      microglia-exaggerated release of inflammatory mediators in the pathogenesis of
      Parkinson's disease (PD). Pituitary adenylate cyclase activating polypeptide
      (PACAP) is an endogenous 38 amino acid containing neuropeptide that has been
      shown to possess neurotrophic as well as neuroprotective properties. In this
      study, we sought to determine whether PACAP could protect SH-SY5Y dopaminergic
      cells against toxicity induced by inflammatory mediators. For this purpose, THP-1
      cells which possess microglia-like property were stimulated by a combination of
      lipopolysaccharide (LPS) and interferon gamma (IFN-gamma), and the media
      containing inflammatory mediators were isolated and applied to SH-SY5Y cells.
      Such treatment resulted in approximately 54 % cell death as well as a reduction
      in brain-derived neurotrophic factor (BDNF) and phosphorylated cyclic AMP
      response element-binding protein (p-CREB). Pretreatment of the SH-SY5Y cells with
      PACAP (1-38) dose-dependently attenuated toxicity induced by the inflammatory
      mediators. PACAP effects, in turn, were dose-dependently blocked by the PACAP
      receptor antagonist (PACAP 6-38). These results suggest protective effects of
      PACAP against inflammatory-induced toxicity in a cellular model of PD that is
      likely mediated by enhancement of cell survival markers through activation of
      PACAP receptors. Hence, PACAP or its agonists could be of therapeutic benefit in
      inflammatory-mediated PD.

PMID- 24740429
TI  - Antidepressant and antioxidative effect of Ibuprofen in the rotenone model of
      Parkinson's disease.
AB  - Idiopathic Parkinson's disease is a neurodegenerative disorder that affects
      approximately 1 % of the population over 55 years of age. The disease manifests
      itself through motor and nonmotor symptoms induced mainly by the
      neurodegeneration of dopaminergic neurons in the substantia nigra pars compacta
      (SNpc). The possible mechanisms involved in this pathology include mitochondrial
      dysfunction, neuroinflammation, and oxidative stress. The present study evaluated
      the effects of the nonselective cyclooxygenase inhibitor ibuprofen on motor and
      depressive-like behavior induced by rotenone in rats. Rotenone (2.5 mg/kg, i.p.,
      for 10 days) decreased tyrosine hydroxylase immunoreactivity in the SNpc, and
      ibuprofen treatment (15 mg/kg, p.o., for 22 days) blocked this impairment. We
      also found that rotenone-induced motor deficits (hypolocomotion) and depressive
      like behavior, and ibuprofen was able to reverse these deficits. In addition to
      motor and nonmotor behaviors, we evaluated oxidative stress induced by rotenone.
      Rotenone administration depleted glutathione levels in the hippocampus and
      reduced catalase activity in both the hippocampus and striatum. Post treatment
      with ibuprofen blocked the depletion of glutathione induced by rotenone and
      increased the basal levels of this antioxidant in the striatum. Ibuprofen also
      restored catalase activity. The neuroprotective effects of ibuprofen against
      toxicity induced by rotenone appear to be attributable to its antioxidant
      properties, in addition to cyclooxygenase inhibition. 

PMID- 24740433
TI  - Analysis of unipolar electrograms in rabbit heart demonstrated the key role of
      ventricular apicobasal dispersion in arrhythmogenicity.
AB  - Reduced repolarization reserve and increased transmural dispersion of
      repolarization (TDR) are known risk factors for Torsade de Pointes development,
      but less is known about the role of apex-to-base (apicobasal) repolarization in
      arrhythmogenesis. Three needles were inserted in rabbit left ventricle to record
      unipolar electrograms from endocardium to epicardium and base to apex. Total
      repolarization interval (TRI) and peak-to-end repolarization interval (Tp) were
      assessed after quinidine (n = 6) and D,L-sotalol (n = 6) perfusion in combination
      with the IKs inhibitor chromanol 293B. About 30 uM D,L-sotalol increased TRI and
      Tp more at the base (TRI + 40 +/- 4 %; Tp +89 +/- 11 %) relative to the apex (TRI
      + 28 +/- 3 %, Tp + 30 +/- 8 %). Similar results were obtained with quinidine: TRI
      and Tp increased more at the base compared to the apex. No significant
      differences were recorded from the endocardium to the epicardium. Our results
      show that combined IKr + IKs block prolonged TRI and Tp significantly more at the
      ventricular base than at the apex, in the absence of transmural dispersion of
      refractoriness. Regional changes in TRI and Tp indicate the contribution of
      apicobasal dispersion to arrhythmogenicity compared to TDR in a rabbit heart
      model. 

PMID- 24740432
TI  - Two-step inhibitory effect of kanzo on oxytocin-induced and prostaglandin F2alpha
      induced uterine myometrial contractions.
AB  - We previously reported that shakuyaku-kanzo-to, a kampo medicine consisting of
      shakuyaku and kanzo, has an inhibitory effect on myometrial contractions in
      pregnant women. In this study, we evaluated the effects of kanzo, glycyrrhizin (a
      major component of kanzo), glycyrrhetinic acid (GA; a major metabolite of
      glycyrrhizin), shakuyaku, and paeoniflorin (a major component of shakuyaku) on
      agonist-induced contractions of the uterus of pregnant humans and rats. We
      prepared myometrial strips from the uterus of pregnant humans and rats and
      induced contractions with oxytocin (50 MUU/mL) or prostaglandin F2alpha
      (PGF2alpha) (10(-7) or 10(-6) M). Kanzo (250 MUg/mL) and GA (5 * 10(-6) M)
      inhibited the oxytocin-induced and PGF2alpha-induced contractions in pregnant
      human and rat myometrium, but shakuyaku (250 MUg/mL), paeoniflorin (10(-5) M),
      and glycyrrhizin (10(-5) M) did not inhibit contractions in either.
      Interestingly, kanzo and GA showed an inhibitory effect after temporarily
      enhancing the PGF2alpha-induced contractions in the rat myometrium, but not in
      the human myometrium. These results suggest that kanzo has at least a two-step
      inhibitory effect on the myometrial contractions that originate from the kanzo
      itself and a metabolite of glycyrrhizin in kanzo. Furthermore, kanzo was found to
      be safe for inhibiting PGF2alpha-induced contractions in humans because it did
      not temporarily enhance PGF2alpha-induced contractions. 

PMID- 24740434
TI  - The "innocent" role of Sc(3+) on a non-heme Fe catalyst in an O2 environment.
AB  - Density functional theory calculations have been used to investigate the reaction
      mechanism proposed for the formation of an oxoiron(iv) complex [Fe(IV)(TMC)O](2+)
      (P) (TMC = 1,4,8,11-tetramethylcyclam) starting from a non-heme reactant complex
      [Fe(II)(TMC)](2+) (R) and O2 in the presence of acid H(+) and reductant BPh4(-).
      We also addressed the possible role of redox-inactive Sc(3+) as a replacement for
      H(+) acid in this reaction to trigger the formation of P. Our computational
      results substantially confirm the proposed mechanism and, more importantly,
      support that Sc(3+) could trigger the O2 activation, mainly dictated by the
      availability of two electrons from BPh4(-), by forming a thermodynamically stable
      Sc(3+)-peroxo-Fe(3+) core that facilitates O-O bond cleavage to generate P by
      reducing the energy barrier. These insights may pave the way to improve the
      catalytic reactivity of metal-oxo complexes in O2 activation at non-heme centers.

PMID- 24740435
TI  - High resolution, large deformation 3D traction force microscopy.
AB  - Traction Force Microscopy (TFM) is a powerful approach for quantifying cell
      material interactions that over the last two decades has contributed
      significantly to our understanding of cellular mechanosensing and
      mechanotransduction. In addition, recent advances in three-dimensional (3D)
      imaging and traction force analysis (3D TFM) have highlighted the significance of
      the third dimension in influencing various cellular processes. Yet irrespective
      of dimensionality, almost all TFM approaches have relied on a linear elastic
      theory framework to calculate cell surface tractions. Here we present a new high
      resolution 3D TFM algorithm which utilizes a large deformation formulation to
      quantify cellular displacement fields with unprecedented resolution. The results
      feature some of the first experimental evidence that cells are indeed capable of
      exerting large material deformations, which require the formulation of a new
      theoretical TFM framework to accurately calculate the traction forces. Based on
      our previous 3D TFM technique, we reformulate our approach to accurately account
      for large material deformation and quantitatively contrast and compare both
      linear and large deformation frameworks as a function of the applied cell
      deformation. Particular attention is paid in estimating the accuracy penalty
      associated with utilizing a traditional linear elastic approach in the presence
      of large deformation gradients. 

PMID- 24740437
TI  - Bidirectional associations between parental warmth, callous unemotional behavior,
      and behavior problems in high-risk preschoolers.
AB  - Research suggests that parental warmth and positive parent-child interactions
      predict the development of conscience and empathy. Recent studies suggest that
      affective dimensions of parenting, including parental warmth, are associated with
      fewer behavior problems among children with high levels of callous-unemotional
      (CU) behavior. Evidence also suggests that CU behavior confers risk for behavior
      problems by uniquely shaping parenting. The current study examines reciprocal
      associations between parental warmth, CU behavior, and behavior problems among
      toddlers. Data from mother-child dyads (N = 731; 49 % female) were collected from
      a multi-ethnic, high-risk sample at ages 2 and 3. CU behavior was assessed using
      a previously validated measure (Hyde et al. 2013). Models were tested using two
      measures of parental warmth, the first from direct observations of warmth in the
      home, the second coded from 5-min speech samples. Three-way cross-lagged,
      simultaneous effects models showed that parental warmth predicted child CU
      behavior, over and above associations with behavior problems. There were cross
      lagged associations between directly observed parental warmth and child CU
      behavior, suggesting these behaviors show some malleability during toddlerhood
      and that parenting appears to reflect some adaptation to child behavior. The
      results have implications for models of early-starting behavior problems and
      preventative interventions for young children. 

PMID- 24740438
TI  - Evaluating clinically significant change in mother and child functioning:
      comparison of traditional and enhanced behavioral parent training.
AB  - The Strategies to Enhance Positive Parenting (STEPP) program, an enhanced
      behavioral parent training (BPT) intervention, was developed to improve
      engagement in and outcomes following treatment for single-mother families of
      school-age youth with attention-deficit/hyperactivity disorder (ADHD). A previous
      randomized clinical trial of the STEPP program demonstrated that the intervention
      resulted in statistically significant improvements at the group-level in child
      oppositional behavior, various areas of child impairment, parental stress, and
      parenting behavior, relative to a wait-list control condition and a traditional
      BPT group. Despite benefits at the group-level, little is known about outcomes at
      the individual-level of enhanced BPT relative to traditional BPT for various
      child- and parent-level outcomes. The current study compares the extent to which
      traditional BPT and the STEPP program result in reliable change and recovery
      across various child- and parent-level outcomes in a sample of 80, 5-12 year old
      youth with ADHD (70 % male). Analyses demonstrated the benefit of participating
      in either BPT treatment; and participation in the STEPP program compared to
      traditional BPT was associated with only minimal incremental clinical benefit.
      Results, as well as clinical and research implications for assessment and
      treatment of high-risk families of youth with ADHD enrolled in BPT are discussed.

PMID- 24740439
TI  - Boost up mobility of solution-processed metal oxide thin-film transistors via
      confining structure on electron pathways.

PMID- 24740440
TI  - Ring-closing metathesis for the synthesis of a molecular gyrotop.
AB  - Macrocage molecules with a bridged phenylene rotor have been synthesized as
      molecular gyrotops, whose cages were constructed by ring-closing metathesis (RCM)
      of bis(trialkenylsilyl)benzenes. An analysis of the yields of the products in the
      RCM reaction under various temperature conditions revealed that the desired cage,
      i.e., a molecular gyrotop, was produced in good yield under reflux, indicating
      that the cage is a thermodynamically controlled product. 

PMID- 24740441
TI  - Prevalence of neural tube defect in southern Thailand: a population-based survey
      during 2009-2012.
AB  - BACKGROUND: Neural tube defects (NTDs) are a group of congenital malformation of
      the central nervous system that leads to permanent physical disability and
      requires lifelong treatment. In Thailand, there have been three published
      articles on NTDs, all hospital-based studies, which found prevalence of NTDs of
      4.8-6.7 per 10,000 live births. OBJECTIVE: It was our purpose with this study to
      determine the prevalence and type of NTDs in southern Thailand through a
      population-based survey. METHOD: Data were obtained through the population-based
      surveillance during 2009-2012 in three provinces (Songkhla, Phatthalung, Trang)
      in southern Thailand. Entries in the birth defects registry included all live
      births, all stillbirths after 24-week gestational age, and termination of
      pregnancy following the prenatal diagnosis at any gestational age of all
      congenital anomalies. RESULTS: During 2009-2012, 148,759 births were registered
      in the three provinces. Twenty-eight NTD cases were identified, giving an average
      of 1.88 per 10,000 births (95 % CI 1.20-2.51): 12 cases with anencephaly (42.8
      %), 5 with occipital encephalocele (17.9 %), and 11 with myelomeningocele (39.3
      %). The birth prevalence per 10,000 births of anencephaly, encephalocele, and
      myelomeningocele were 0.81, 0.33, and 0.74, respectively. Sixteen (57 %) were
      detected in live births, and 12 (43 %) were detected by prenatal diagnosis which
      later resulted in termination of pregnancy. CONCLUSIONS: The prevalence of NTDs
      based on the population-based study in southern Thailand was low. About 40 % of
      NTD cases were detected prenatally and later terminated. Hence, examining only
      registry live births will result in an inaccurately low NTD prevalence rate.

PMID- 24740442
TI  - Skull base embryology: a multidisciplinary review.
AB  - INTRODUCTION: The skull base represents a central and complex bone structure of
      the skull and forms the floor of the cranial cavity on which the brain lies.
      Anatomical knowledge of this particular region is important for understanding
      several pathologic conditions as well as for planning surgical procedures.
      Embryology of the cranial base is of great interest due to its pronounced impact
      on the development of adjacent regions including the brain, neck, and
      craniofacial skeleton. MATERIALS AND METHODS: Information from human and
      comparative anatomy, anthropology, embryology, surgery, and computed modelling
      was integrated to provide a perspective to interpret skull base formation and
      variability within the cranial functional and structural system. RESULTS AND
      CONCLUSIONS: The skull base undergoes an elaborate sequence of development stages
      and represents a key player in skull, face and brain development. Furthering our
      holistic understanding of the embryology of the skull base promises to expand our
      knowledge and enhance our ability to treat associated anomalies.

PMID- 24740443
TI  - Antiretroviral drug resistance among antiretroviral-naive and treatment
      experienced patients infected with HIV in Iran.
AB  - Resistance to antiretroviral therapy (ART) threatens the success of programs to
      reduce HIV morbidity and mortality, particularly in countries with few treatment
      options. In the present study, genotype and phenotype data from ART-naive and
      experienced hospitalized patients infected with HIV in Tehran, Iran were used to
      assess the prevalence and types of transmitted (TDR) and acquired drug resistance
      (ADR) mutations. All 30 participants naive to ART and 62 of 70 (88.6%)
      participants receiving ART had detectable viral loads. Among participants
      receiving ART with sequencing data available (n = 62), 36 (58.1%) had at least
      one drug resistance mutation; the most common mutations were K103N (21.0%), M184V
      (19.4%), and the thymidine analogue mutations. Seven (11.3%), 27 (43.5%), and two
      (3.2%) of these participants had resistance to one, two, and three drug classes,
      respectively. High-level resistance to efavirenz (EFV) was more common among
      participants on EFV-based regimens than high-level lopinavir/ritonivar (LPV/r)
      resistance among those on LPV/r-based regimens (55.3% vs. 6.7%, P < 0.0001). Two
      (6.7%) antiretroviral-naive participants had K103N mutations. These findings
      document an alarmingly high frequency of multiple HIV drug class resistance in
      Iran, confirm the presence of TDR, and highlight the need for systematic viral
      load monitoring and drug resistance testing, including at diagnosis. Expanded
      access to new antiretroviral medications from additional drug classes is needed.

PMID- 24740444
TI  - Robotically assisted laparoscopic repair of anterior vaginal wall and uterine
      prolapse by lateral suspension with mesh: initial experience and video.
AB  - INTRODUCTION AND HYPOTHESIS: Sacral colpopexy/hysteropexy is a well-established
      approach to vaginal apex support and was the first technique used to treat pelvic
      organ prolapse (POP) with robotic assistance. However, dissection at the level of
      the promontory may be difficult, especially in obese patients, and associated
      with rare but potential serious morbidity such as life-threatening vascular
      injury. In an attempt to avoid this risk, we describe a new robotic approach for
      POP repair with lateral suspension. METHODS: From March 2012 through June 2013,
      ten patients with symptomatic anterior vaginal wall and uterine prolapse were
      operated by a single surgeon. The video presents the different steps of
      robotically assisted laparoscopic repair of POP by lateral suspension with mesh
      and uterine conservation using da Vinci S or Si system. RESULTS: POP repair was
      successfully completed in all ten patients without any perioperative or
      postoperative complication. CONCLUSION: Robotically assisted laparoscopic repair
      of POP by lateral suspension with mesh is a novel and feasible technique with
      promising short-term results. It may have several theoretical advantages over
      sacral colpopexy/hysteropexy and may represent an alternative in cases of
      difficult dissection of the promontory.

PMID- 24740445
TI  - UR-CHOICE: can we provide mothers-to-be with information about the risk of future
      pelvic floor dysfunction?
AB  - Vaginal childbirth is probably the most important factor in the aetiology of
      pelvic floor dysfunction (PFD) and results in the combination of some or all of
      the following conditions: urinary (UI) and faecal (FI) incontinence and pelvic
      organ prolapse (POP). Up until now, it has been difficult to counsel women
      antenatally regarding risk factors for subsequent PFD, as there has been little
      good-quality, long-term information available. We now have moderately robust
      epidemiological data at 12 and 20 years after delivery and objective
      pathophysiological data (pudendal nerve trauma and levator defects/avulsion). In
      this commentary, we propose a scoring system (UR-CHOICE) to predict the risk of
      future PFD based on several major risk factors (UI before pregnancy, ethnicity,
      age at birth of first child, body mass index, family history (mother and sister)
      of PFD and baby's weight and maternal height (if <160 cm and baby >4 kg) that
      have been identified for subsequent PFD risk. This scoring system will help with
      counselling for women regarding PFD prevention.

PMID- 24740446
TI  - Antecedent interventions for pediatric feeding problems.
AB  - Behavior analysts have implemented and evaluated several antecedent strategies
      for treating pediatric feeding problems. The extent to which antecedent
      interventions are beneficial, however, is not yet clear. This review examines
      recent research in the Journal of Applied Behavior Analysis (2000-2012) that
      evaluated antecedent interventions. We found that the feeding diagnosis (food
      refusal vs. food selectivity) and presence of feeding-related medical conditions
      were related to the differential implementation of antecedent interventions. 

PMID- 24740447
TI  - Tacrolimus-related adverse effects in liver transplant recipients: its
      association with trough concentrations.
AB  - BACKGROUND: Tacrolimus is an important immunosuppressant administered to patients
      following liver transplantation (LT), with a recommended trough concentration of
      8 to 11 ng/mL to prevent allograft rejection. We retrospectively examined our
      data to identify the tacrolimus trough concentration that combined efficacy with
      minimal adverse effects. METHODS: The case records of LT recipients, who were
      nondiabetic, nonhypertensive, and with normal renal parameters prior to LT were
      retrospectively examined for acute cellular rejection (ACR) episodes and three
      major adverse effects of tacrolimus, i.e. neurotoxicity, nephrotoxicity, and new
      onset diabetes mellitus (NODM). RESULTS: Thirty-two LT recipients fulfilled the
      criteria for the study. The mean (+/-SD) tacrolimus level for the 290 troughs
      (after 10 days) was 8.5 +/- 3.8 ng/mL. At 10 days, 1 month, 3 months, and 6
      months, the trough values were 7.3 +/- 2.9, 9.7 +/- 3.4, 7.9 +/- 3.3, and 7.6 +/-
      2.6 ng/mL, respectively. The mean time taken for stabilization of the blood
      pressure and biochemical parameters was 7 +/- 2 days. Overall, a trough window
      with the least adverse effect was 7 to 7.9 ng/mL. Neurotoxicity was least in the
      trough range 5 to <8 ng/mL. Symptoms included headache in four, tremors in three,
      seizure in one, confusion and psychosis in two, and combination in three.
      Nephrotoxicity was least in trough 8 to <11 ng/mL. One patient progressed to
      chronic kidney disease at 6 months. NODM was present in 11 % to 18 % across the
      various trough range, including the extremes (mean trough level, 8.4 +/- 4.4
      ng/dL). At 6 months, five recipients were on treatment for NODM. Three recipients
      developed ACR, two within the first month and one at 7 weeks. The trough levels
      were 8.5, 9, 15.2 ng/mL, respectively. All recovered with three pulse doses of
      methylprednisolone. CONCLUSION: Tacrolimus concentration of 5 to <8 ng/mL was
      associated with least overall toxicity, neurotoxicity, and ACR.

PMID- 24740448
TI  - Brief report: Parthenogenetic embryonic stem cells are an effective cell source
      for therapeutic liver repopulation.
AB  - Parthenogenesis is the development of an oocyte without fertilization. Mammalian
      parthenogenetic (PG) embryos are not viable, but can develop into blastocysts
      from which embryonic stem cells (ESCs) have been derived in mouse and human. PG
      ESCs are frequently homozygous for alleles encoding major histocompatibility
      complex (MHC) molecules. MHC homozygosity permits much more efficient immune
      matching than MHC heterozygosity found in conventional ESCs, making PG ESCs a
      promising cell source for cell therapies requiring no or little immune
      suppression. However, findings of restricted differentiation and proliferation of
      PG cells in developmental chimeras have cast doubt on the potential of PG ESC
      derivatives for organ regeneration. To address this uncertainty, we determined
      whether PG ESC derivatives are effective in rescuing mice with lethal liver
      failure due to deficiency of fumarylacetoacetate hydrolase (Fah). In
      developmental chimeras generated by injecting wild-type PG ESCs into Fah
      deficient blastocysts, PG ESCs differentiated into hepatocytes that could
      repopulate the liver, provide normal liver function, and facilitate long-term
      survival of adult mice. Moreover, after transplantation into adult Fah-deficient
      mice, PG ESC-derived hepatocytes efficiently engrafted and proliferated, leading
      to high-level liver repopulation. Our results show that--despite the absence of a
      paternal genome--PG ESCs can form therapeutically effective hepatocytes.

PMID- 24740449
TI  - Simultaneous study of subcellular exocytosis with individually addressable
      multiple microelectrodes.
AB  - We report the application of individually addressable microelectrode arrays
      (MEAs) to study the heterogeneity of cell exocytosis at the subcellular level.
      Multiple subcellular-size electrodes are covered by a single PC12 cell for the
      investigation of subcellular exocytosis. PC12 cells have been seeded and cultured
      on top of three kinds of MEAs containing 16, 25, or 36 square microelectrodes (4
      MUm width in a 4 by 4 MEA, 3 MUm width in a 5 by 5 MEA, 2 MUm width in a 6 by 6
      MEA). After collagen coating, single cells were found to cover several electrodes
      and these were selected for the study of subcellular exocytosis. Amperometric
      results show that single cell and subcellular heterogeneity in single cell
      exocytosis can be electrochemically detected with these MEAs. The results also
      show that these MEAs are suitable for detecting fast chemical events at single
      cells, as well as for developing multifunctional electrochemical sensors. 

PMID- 24740451
TI  - Chocolate milk consequences: a pilot study evaluating the consequences of banning
      chocolate milk in school cafeterias.
AB  - OBJECTIVES: Currently, 68.3% of the milk available in schools is flavored, with
      chocolate being the most popular (61.6% of all milk). If chocolate milk is
      removed from a school cafeteria, what will happen to overall milk selection and
      consumption? METHODS: In a before-after study in 11 Oregon elementary schools,
      flavored milk-which will be referred to as chocolate milk-was banned from the
      cafeteria. Milk sales, school enrollment, and data for daily participation in the
      National School Lunch Program (NSLP) were compared year to date. RESULTS: Total
      daily milk sales declined by 9.9% (p<0.01). Although white milk increased by
      161.2 cartons per day (p<0.001), 29.4% of this milk was thrown away. Eliminating
      chocolate milk was also associated with 6.8% fewer students eating school
      lunches, and although other factors were also involved, this is consistent with
      the notion of psychological reactance. CONCLUSIONS: Removing chocolate milk from
      school cafeterias may reduce calorie and sugar consumption, but it may also lead
      students to take less milk overall, drink less (waste more) of the white milk
      they do take, and no longer purchase school lunch. Food service managers need to
      carefully weigh the costs and benefits of eliminating chocolate milk and should
      consider alternative options that make white milk more convenient, attractive,
      and normal to choose.

PMID- 24740450
TI  - Characterizing the relationship between free drug samples and prescription
      patterns for acne vulgaris and rosacea.
AB  - IMPORTANCE: Describing the relationship between the availability of free
      prescription drug samples and dermatologists' prescribing patterns on a national
      scale can help inform policy guidelines on the use of free samples in a
      physician's office. OBJECTIVES: To investigate the relationships between free
      drug samples and dermatologists' local and national prescribing patterns and
      between the availability of free drug samples and prescription costs. DESIGN,
      SETTING, AND PARTICIPANTS: Cross-sectional study investigating prescribing
      practices for acne, a common dermatologic condition for which free samples are
      often available. The settings were, first, the offices of nationally
      representative dermatologists from the National Disease and Therapeutic Index (an
      IMS Health Incorporated database) and, second, an academic medical center clinic
      without samples. Participants were ambulatory patients who received a
      prescription from a dermatologist for a primary initial diagnosis of acne
      vulgaris or rosacea in 2010. MAIN OUTCOMES AND MEASURES: National trends in
      dermatologist prescribing patterns, the degree of correlation between the
      availability of free samples and the prescribing of brand-name medications, and
      the mean cost of acne medications prescribed per office visit nationally and at
      an academic medical center without samples. RESULTS: On a national level, the
      provision of samples with a prescription by dermatologists has been increasing
      over time, and this increase is correlated (r = 0.92) with the use of the branded
      generic drugs promoted by these samples. Branded and branded generic drugs
      comprised most of the prescriptions written nationally (79%), while they
      represented only 17% at an academic medical center clinic without samples.
      Because of the increased use of branded and branded generic drugs, the national
      mean total retail cost of prescriptions at an office visit for acne was
      conservatively estimated to be 2 times higher (approximately $465 nationally vs
      $200 at an academic medical center without samples). CONCLUSIONS AND RELEVANCE:
      Free drug samples can alter the prescribing habits of physicians away from the
      use of less expensive generic medications. The benefits of free samples in
      dermatology must be weighed against potential negative effects on prescribing
      behavior and prescription costs.

PMID- 24740452
TI  - Individual aortic baroreceptors are sensitive to different ranges of blood
      pressures.
AB  - Many receptors, including thermal receptors and mechanical receptors, are only
      activated by stimuli within a clearly defined range of intensities. Differences
      in the receptive ranges enable individual receptors and their sensory centers to
      precisely detect the intensity of the stimulus and changes in intensity.
      Baroreceptors are the sensory terminals of the baroreflex. It is well understood
      that an increasing number of baroreceptors are recruited to produce afferent
      action potentials as the blood pressure increases, indicating that individual
      baroreceptors have different pressure thresholds. The present study revealed that
      individual baroreceptors could stop their afferent signals when the blood
      pressure exceeds a certain level, indicating that individual baroreceptors are
      sensitive to a specific range of blood pressure. The receptive ranges of
      individual baroreceptors differ in terms of the total range, the lower threshold,
      and the upper threshold. Of 85 baroreceptors examined in this study, the upper
      thresholds for about half were within the physiological blood pressure range.
      These results indicate that supraphysiological blood pressure is unlikely to be
      encoded by the recruitment of more baroreceptors. Instead, supraphysiological
      blood pressure levels might be signaled by an increase in the frequency of action
      potentials or by other mechanisms. In conclusion, our results indicate that
      rabbit baroreceptors are activated by blood pressure levels within specific
      receptive ranges. These findings should encourage further studies to examine the
      role of population coding of blood pressure by baroreceptors in the baroreflex. 

PMID- 24740453
TI  - Activation of STAT3 stimulates AHSP expression in K562 cells.
AB  - Studies on the chaperone protein alpha-hemoglobin stabilizing protein (AHSP)
      reveal that abundant AHSP in erythroid cells enhance the cells' tolerance to
      oxidative stress imposed by excess alpha-hemoglobin in pathological conditions.
      However, the potential intracellular modulation of AHSP expression itself in
      response to oxidative stress is still unknown. The present study examined the
      effect and molecular mechanism of STAT3, an oxidative regulator, on the
      expression of AHSP. AHSP expression increased in K562 cells upon cytokine IL-6
      induced STAT3 activation and decreased in STAT3 knock-down K562 cells. Regulation
      of AHSP in oxidative circumstance was then examined in alpha-globin-overloaded
      K562 cells, and real-time PCR showed strengthened expression of both AHSP and
      STAT3. ChIP analysis showed binding of STAT3 to AHSP promoter and binding was
      significantly augmented with IL6 stimulation and upon alpha-globin
      overexpression. Dual luciferase reporter assays of the wildtype and mutated SB3
      element, an IL-6RE site, in the AHSP promoter in K562 cells highlighted the
      direct regulatory effect of STAT3 on AHSP gene. Finally, direct binding of STAT3
      to SB3 site of AHSP promoter was confirmed with EMSA assays. Our work reveals an
      adaptive AHSP regulation mediated by the redox-sensitive STAT3 signaling pathway,
      and provides clues to the therapeutic strategy for AHSP enhancement. 

PMID- 24740454
TI  - A clinical study of patients with coronary heart disease complicated with
      hypertriglyceridemic waist phenotype.
AB  - The objective of this study was to investigate the characteristics of coronary
      lesions in patients with coronary heart disease complicated with
      hypertriglyceridemic waist phenotype and determine the relation to risk factors.
      For this purpose, 105 patients with >= 50 % stenosis in one branch of coronary
      arteries as confirmed by coronary angiography were enrolled. Further, in this
      regard, 41 cases (i.e., case group) were complicated with hypertriglyceridemic
      waist phenotype, while 64 patients (i.e., control group) were not complicated
      with this phenotype. The data show that, as compared with control group, the
      patients in case group had higher coronary artery scores. The coronary lesions in
      case group were associated with waist triglycerides index and tumor necrosis
      factor (TNF)-alpha; partial regression coefficients were 0.774 (P < 0.001) and
      0.250 (P = 0.001), respectively. Therefore, it was concluded that the patients
      with hypertriglyceridemic waist phenotype had a worse coronary heart disease
      condition, whereas waist triglycerides index and TNF-alpha related closely to the
      severity of coronary lesions.

PMID- 24740455
TI  - What about sparsity when data are curves?
AB  - This is a discussion around the paper "Overview of object oriented data analysis"
      by J. Steve Marron and Andres M. Alonso. 

PMID- 24740456
TI  - CacyBP/SIP protein is important for the proliferation of human glioma cells.
AB  - Recently, calcyclin-binding protein or Siah-1-interacting protein (CacyBP/SIP), a
      component of a novel ubiquitinylation pathway, could regulate the beta-catenin
      degradation (Fukushima et al., Immunity 2006, 24, 29-39). However, the potential
      role of CacyBP/SIP itself in human glioma cells has not been clarified. Here, we
      found that CacyBP/SIP was expressed highly in human glioma tissues. Silencing of
      CacyBP/SIP by short-hairpin RNA severely suppressed the proliferation of human
      glioma cell U251, which was at least partly mediated by downregulation of phospho
      Akt (p-Akt) and phospho-beta-catenin (p-beta-catenin) as well as upregulation of
      p53 and p21. Furthermore, overexpression of CacyBP/SIP obviously promoted the
      proliferation of human glioma U251, which exhibited the exactly contrary trend in
      the expression of p-Akt, p-beta-catenin, p53, and p21. Taken together, these
      findings suggest that CacyBP/SIP plays important roles in the proliferation of
      human glioma cell which might be involved in the development of human glioma.

PMID- 24740457
TI  - Maternal intake of vitamin E and birth defects, national birth defects prevention
      study, 1997 to 2005.
AB  - BACKGROUND: In a recent study, high maternal periconceptional intake of vitamin E
      was found to be associated with risk of congenital heart defects (CHDs). To
      explore this association further, we investigated the association between total
      daily vitamin E intake and selected birth defects. METHODS: We analyzed data from
      4525 controls and 8665 cases from the 1997 to 2005 National Birth Defects
      Prevention Study. We categorized estimated periconceptional energy-adjusted total
      daily vitamin E intake from diet and supplements into quartiles (referent, lowest
      quartile). Associations between quartiles of energy-adjusted vitamin E intake and
      selected birth defects were adjusted for demographic, lifestyle, and nutritional
      factors. RESULTS: We observed a statistically significant association with the
      third quartile of vitamin E intake (odds ratio [OR], 1.17; 95% confidence
      interval [CI], 1.01-1.35) and all CHDs combined. Among CHD sub-types, we observed
      associations with left ventricular outflow tract obstruction defects, and its sub
      type, coarctation of the aorta and the third quartile of vitamin E intake. Among
      defects other than CHDs, we observed associations between anorectal atresia and
      the third quartile of vitamin E intake (OR, 1.66; 95% CI, 1.01-2.72) and
      hypospadias and the fourth quartile of vitamin E intake (OR, 1.42; 95% CI, 1.09
      1.87). CONCLUSION: Selected quartiles of energy-adjusted estimated total daily
      vitamin E intake were associated with selected birth defects. However, because
      these few associations did not exhibit exposure-response patterns consistent with
      increasing risk associated with increasing intake of vitamin E, further studies
      are warranted to corroborate our findings.

PMID- 24740458
TI  - Comparing acquisition of AAC-based mands in three young children with autism
      spectrum disorder using iPad(r) applications with different display and design
      elements.
AB  - Augmentative and alternative communication (AAC) applications may differ in their
      use of display and design elements. Using a multielement design, this study
      compared mand acquisition in three preschool-aged males with autism spectrum
      disorder, across three different displays in two iPad((r)) AAC applications.
      Displays included a Widgit symbol button (GoTalk), a photographical hotspot
      (Scene and Heard), and a Widgit symbol button along with a photograph (Scene and
      Heard). Applications had additional design differences. Two participants showed
      more rapid and consistent acquisition with the photographical hotspot than with
      the symbol button format, but did not master the combined format. The third
      participant mastered all three conditions at comparable rates. Results suggest
      that AAC display and design elements may influence mand acquisition. 

PMID- 24740459
TI  - Photobehaviour of methyl-pyridinium and quinolinium iodide derivatives, free and
      complexed with DNA. A case of bisintercalation.
AB  - Excited state dynamics of four azinium salts were studied in buffered water and
      in the presence of salmon testes DNA. Complexation with DNA changes the
      photobehaviour of the free ligands lowering the photoreactivity and emission in
      favor of internal conversion. The interaction of these four dyes with DNA was
      studied with different techniques with the aim to establish the affinity and the
      type of binding between the ligands and DNA. The results from spectrophotometric
      and fluorimetric titrations provided evidence of a strong interaction between the
      azinium salts and the polynucleotide, with a binding constant of about 10(6) M(
      1), making them interesting for therapeutical applications. Dichroic measurements
      allowed us to determine the possible modes of binding for each complex. Short
      living excited states of the free dyes were detected and characterized by
      ultrafast absorption spectroscopy. A further decrease of transient lifetimes was
      observed upon interaction with DNA. The bicationic pyridinium iodide was found to
      act as a bisintercalative agent, potentially increasing the cytotoxicity with low
      dose and less collateral effects. 

PMID- 24740460
TI  - Effects of benzo-annelation of asymmetric phthalocyanine on the photovoltaic
      performance of dye-sensitized solar cells.
AB  - Novel highly asymmetric zinc tetraazaporphyrin (TAP) derivatives (Zn-tri-TAPNc
      and Zn-tri-PcNc) with one carboxyl and three tert-butyl peripheral substituent
      groups were synthesized. A highly asymmetric zinc phthalocyanine (ZnPc)
      derivative (Zn-tri-PcNc) has a benzo-annelated ring which contains
      tribenzonaphtho-condensed tetraazaporphyrin with the same peripheral substituents
      as Zn-tri-TAPNc. As a sensitizer for the TiO2-based dye-sensitized solar cell, Zn
      tri-PcNc derived from the benzo-annelation of the TAP macrocycle showed improved
      light harvesting and electron injection efficiency, which can retard the charge
      recombination, resulting in a great improvement in the incident photon-to-current
      conversion efficiency (IPCE). The Zn-tri-PcNc-sensitized solar cell exhibited a
      higher conversion efficiency (2.89%) than the Zn-tri-TAPNc-sensitized one (1.20%)
      under AM 1.5G solar irradiation. The present results on the TAP macrocycle's
      benzo-annelation demonstrate that optimization of molecular structure via
      changing the peripheral substituent group's "push-pull" effect and enlarging the
      conjugated pi-system is an effective approach to improve the performance of the
      tetraazaporphyrin-based dye-sensitized solar cell. 

PMID- 24740461
TI  - WITHDRAWN: Preventive staff-support interventions for health workers.

PMID- 24740462
TI  - Diagnostic validity of colchicine in patients with Familial Mediterranean fever.
AB  - Although response to colchicine has been proposed as one of the diagnostic
      criteria in patients with Familial Mediterranean fever (FMF), the validity of
      this response has not been validated. The aim of this study was to assess the
      efficacy of the response to colchicine and to evaluate the extent of the effect
      of placebo. A double-blind randomized placebo-controlled trial with a cross-over
      design was conducted. The frequency of FMF attacks, the disease score, physical
      examination, and acute phase reactants were assessed at 0, 3, and 6 months. Blood
      samples were collected for complete blood count (CBC), erythrocyte sedimentation
      rate (ESR), levels of serum C-reactive protein (CRP) and serum amyloid A (SAA),
      and MEFV mutation analysis in 79 patients with a preliminary diagnosis of FMF.
      Patients were randomly allocated to receive either drug A or drug B in a double
      blind fashion. The designated drug was switched at 3 months. Patients taking
      colchicine had less frequent FMF attacks (median 0) and lower FMF disease score
      (median 0) when compared to those on placebo (median 1 and 3, respectively) (p =
      0.002 and p = 0.007, respectively). In genetically confirmed FMF patients, median
      attack number and median disease score was 0 under colchicine treatment, whereas
      these parameters were significantly higher in the placebo group (median 2 and 8,
      respectively) (p = 0.007 and p = 0.02, respectively) suggesting that colchicine
      is more effective than placebo in reducing attacks and disease score. Positive
      and negative predictive values were 70.2 and 37.5 %, respectively. During the
      placebo period, patients had less FMF attacks when compared to that of the pre
      study period (median 2 vs 6, respectively) (p < 0.001). The high false positive
      rate raises concerns for considering the colchicine response test as diagnostic
      for FMF. The role of placebo on the attacks of periodic fever syndromes needs to
      be further investigated. 

PMID- 24740463
TI  - Successful platelet count recovery in lupus-associated thrombocytopenia with the
      thrombopoietin agonist eltrombopag.
AB  - Eltrombopag is a new thrombomimetic medication approved for the treatment of
      immune thrombocytopenia. There are very few reports on the use of eltrombopag in
      patients with thrombocytopenia associated with sytemic lupus.We present a recent
      case of a patient with lupus with severe thrombocytopenia refractory to
      conventional therapy and full recovery with the use of eltrombopag. The present
      status of the literature with the use of this medication in patients with lupus
      is reviewed and discussed.

PMID- 24740464
TI  - Transcatheter closure of tortuous aorto-right atrial fistula.
AB  - Congenital fistula between the aorta and right atrium is a rare congenital
      anomaly of the heart. We report a new case of this unusual communication, which
      was successfully closed by transcatheter embolisation using an Amplatzer duct
      occluder II. A 7-year-old asymptomatic girl was referred to our institute for
      evaluation of a murmur. Echocardiography revealed intact septae and the right
      coronary sinus was dilated with a fistulous tract arising from the sinus and
      opening into the right atrium with continuous flow into the right atrium.
      Computerized tomography confirmed the diagnosis and delineated the anatomy.
      Cardiac catheterization performed confirmed the presence of a markedly tortuous
      and dilated aorto-right atrial fistula. Coronary angiography demonstrated normal
      coronary arteries arising from the respective sinuses. The fistula was closed
      antegradely using an Amplatzer duct occluder II (AGA Medical Corporation,
      Plymouth, MN, USA). The continuous murmur had disappeared after the procedure and
      an echocardiogram revealed no continuous flow across the fistulous tract. The
      patient remained well at follow-up 3 months later.

PMID- 24740465
TI  - Self-powered cardiac pacemaker enabled by flexible single crystalline PMN-PT
      piezoelectric energy harvester.
AB  - A flexible single-crystalline PMN-PT piezoelectric energy harvester is
      demonstrated to achieve a self-powered artificial cardiac pacemaker. The energy
      harvesting device generates a short-circuit current of 0.223 mA and an open
      circuit voltage of 8.2 V, which are enough not only to meet the standard for
      charging commercial batteries but also for stimulating the heart without an
      external power source. 

PMID- 24740466
TI  - Sirolimus Immunoprophylaxis and Renal Histological Changes in Long-Term Cardiac
      Transplant Recipients: A Pilot Study.
AB  - BACKGROUND: The effects of sirolimus (SIR), as a substitution for calcineurin
      inhibitor (CNI) immunoprophylaxis, on renal function in very-long-term cardiac
      transplant recipients have been a matter of controversy. OBJECTIVE: To assess the
      impacts of SIR as a substitution for CNI on renal function up to 24 months in
      long-term cardiac recipients as well as the renal histological changes in
      patients with suspected CNI-induced nephrotoxicity. METHODS: A total of 23
      cardiac transplant recipients aged 57.7 +/- 11.2 years, 91 months post-cardiac
      transplantation were recruited; 15 patients were randomized to CNI-free immune
      suppression with SIR, and 8 patients were allocated to continue their CNI
      regimens. Serum creatinine and calculated serum creatinine clearance were
      measured at prespecified time points up to 24 months. Renal structure and
      function were assessed by renal biopsies, renal ultrasound, and magnetic
      resonance imaging at baseline. RESULTS: There were no significant changes in
      creatinine clearance during the course of the study in patients treated with SIR.
      However, SIR-treated patients exhibited a significant decrease in 24-hours and
      nighttime systolic and diastolic blood pressures. Typical findings of significant
      hypertensive renal disease were detected in 9 of the 11 (82%) patients. Features
      of chronic CNI toxicity were detected in 6 (55%) patients. CONCLUSIONS: There is
      a very high rate of hypertensive renal disease concomitantly with some degree of
      CNI toxicity in long-term cardiac transplant recipients with renal dysfunction.
      This very high rate of hypertension-related disease may limit the impact of SIR
      on improving renal function long term following cardiac transplantation.

PMID- 24740467
TI  - Diffuse Desquamating Rash Following Exposure to Vancomycin-Impregnated Bone
      Cement.
AB  - OBJECTIVE: To describe a case of systemic desquamating dermatitis following
      implantation of vancomycin antibiotic-laden cement (ABLC) in a patient with prior
      history of Stevens-Johnson (SJS) reaction to vancomycin. CASE SUMMARY: A 59-year
      old man with a history of SJS reaction to systemic vancomycin and recurrent
      methicillin-susceptible Staphylococcus aureus prosthetic knee infection developed
      a painful, blistering rash after implantation of bone cement that had been mixed
      with 2 g of vancomycin. He was started empirically on steroids by his primary
      care provider and had desquamation about 1 week later. DISCUSSION: Systemic
      absorption of antibiotics from ABLC has been well documented in the literature.
      Reports of systemic toxicity are rare, and none have described systemic allergic
      reactions to vancomycin. This patient's prior episode of SJS was diagnosed at
      another academic medical center 6 years ago, and records are unavailable.
      Following low-level reexposure to vancomycin, he developed a diffuse painful
      desquamating rash. Application of the Naranjo nomogram yielded a score of 8
      (probable adverse reaction). Although he did not experience fever, sore throat,
      or mucous membrane involvement to fulfill classic features of SJS, we believe
      that his severe rash represented a less-severe form of a systemic
      hypersensitivity reaction to vancomycin. CONCLUSION: Antibiotics contained in
      ABLC are systemically absorbed, though at low levels, and have been associated
      with systemic toxicities. Antibiotics to which a patient has had a potentially
      life-threatening reaction should not be used in ABLC. Particular attention should
      be paid to an individual's antibiotic allergy history prior to implantation of
      any ABLC.

PMID- 24740468
TI  - Cerebrovascular Accident in a High-Risk Patient During the Early Initiation Phase
      With Canagliflozin.
AB  - OBJECTIVE: To report a case of cerebrovascular accident (CVA) in a high-risk
      patient following initiation of canagliflozin, the first-in-class sodium-glucose
      co-transporter 2 inhibitor approved by the Food and Drug Administration for type
      2 diabetes mellitus. CASE SUMMARY: We describe a 62-year-old woman, with multiple
      clinical risk factors for stroke, who began canagliflozin 300 mg daily in
      addition to basal insulin therapy for diabetes management. The patient developed
      expressive aphasia 15 days following initiation of canagliflozin. Neuroimaging
      revealed acute infarcts of the left basal ganglia and temporal and parietal
      lobes. The patient was diagnosed with a CVA. Canagliflozin therapy was
      discontinued, metformin therapy was reinitiated in addition to the patient's
      basal insulin, and the patient was treated with antiplatelet, statin, and speech
      therapies. DISCUSSION: Assessment of the cardiovascular (CV) safety of
      canagliflozin is currently being investigated. A numerical increase in CV events,
      including nonfatal stroke, has been noted in preliminary data from ongoing
      analyses of canagliflozin in patients with preexisting CV risk factors. Although
      significant clinical risk factors were present in the patient described, a workup
      for routine causality came back negative. According to the Naranjo probability
      score, initiation of canagliflozin had a possible to probable association with
      the patient's CVA. CONCLUSIONS: This case suggests a potential association
      between the timing of canagliflozin initiation and development of stroke in
      patients with multiple clinical risk factors. We advise practitioners to use
      caution when initiating this new agent in patients at high risk for stroke while
      long-term CV safety surveillance is ongoing.

PMID- 24740469
TI  - 3,4-Methylenedioxymethamphetamine's (MDMA's) Impact on Posttraumatic Stress
      Disorder.
AB  - OBJECTIVE: Review the current literature assessing the role of 3,4
      methylenedioxymethamphetamine (MDMA) on posttraumatic stress disorder (PTSD).
      DATA SOURCES: OVID MEDLINE search (1960-February 2014) using the terms MDMA, 3,4
      methylenedioxymethamphetamine, Molly, and Ecstasy crossed with posttraumatic
      stress disorder with backwards citation tracking using references from procured
      articles. STUDY SELECTION AND DATA EXTRACTION: English language studies assessing
      MDMA in patients with PTSD. DATA SYNTHESIS: Three randomized controlled trials
      (RCTs) were conducted along with follow-up open-label and extension evaluations.
      In the 3 RCTs, therapy with MDMA-assisted psychotherapy is promising, with
      reductions in PTSD rating scale scores (Clinician-Administered PTSD Scale,
      Severity of Symptoms Scale for PTSD Scale), although 2 of 3 trials did not show
      significant results, and all three had methodological limitations. The direction
      of effect for all trials was toward benefit in patients who were refractory to
      other PTSD therapies; the percentage reductions on rating scores ranged from 23%
      to 68%; and in 1 trial, the effect was sustained over a long period of time. MDMA
      ingestion without sustained psychotherapy over a 6- to 8-hour period is unlikely
      to be beneficial; trying to prolong the duration of effect with supplemental
      dosing is unlikely to provide additional benefits; and there are adverse effects
      on blood pressure and heart rate that should be appreciated. These studies used
      unadulterated MDMA with known and reproducible potency, which may not happen with
      street purchase of the product. CONCLUSIONS: MDMA-assisted psychotherapy may be
      an effective therapy in refractory PTSD but needs further evaluation to determine
      its place in contemporary therapy.

PMID- 24740470
TI  - Colesevelam, Ezetimibe, and Patients With Type 2 Diabetes Mellitus:
      Characteristics and Clinical Outcomes From a Health Care Database.
AB  - BACKGROUND: Despite the prevalence of therapies available to patients at highest
      coronary heart disease risk, only a minority of type 2 diabetes mellitus (T2DM)
      patients reach desired cholesterol treatment levels, with limited data regarding
      their outcomes. OBJECTIVE: To examine "real-world" effectiveness of initiating
      treatment with either colesevelam or ezetimibe among individuals with evidence of
      T2DM and hypercholesterolemia (HCh). Key outcomes included treatment patterns and
      cardiovascular (CV) events. METHODS: This retrospective administrative claims
      based study utilized medical, pharmacy, and enrollment data linked to laboratory
      results information from a large United States health plan (January 1, 2006, to
      March 31, 2011) and included individuals with recorded evidence of T2DM and HCh.
      The index date was the date of first pharmacy claim for colesevelam or ezetimibe,
      with cohort assignment based on index medication. Assessments included baseline
      characteristics, follow-up treatment patterns, and composite CV event, with
      propensity score matching to correct for sample selection bias. RESULTS: In
      total, 4231 individuals were identified with evidence of HCh and T2DM (ezetimibe
      n = 3384; colesevelam n = 847). After matching, the baseline characteristics
      between cohorts were rendered to be similar. Mean days of persistent medication
      use was lower with colesevelam compared with ezetimibe (P < 0.001). Compared with
      ezetimibe, a smaller percentage of individuals in the colesevelam cohort
      experienced a follow-up composite CV event, and adjusted Cox model results
      suggested decreased risk (hazard ratio = 0.58; P = 0.004) of a follow-up
      composite CV event. CONCLUSION: In this health care database analysis among
      patients with HCh and T2DM, colesevelam was associated with decreased risk of a
      composite CV event compared with ezetimibe, despite lower persistence.

PMID- 24740471
TI  - Increasing consistency of disease biomarker prediction across datasets.
AB  - Microarray studies with human subjects often have limited sample sizes which
      hampers the ability to detect reliable biomarkers associated with disease and
      motivates the need to aggregate data across studies. However, human gene
      expression measurements may be influenced by many non-random factors such as
      genetics, sample preparations, and tissue heterogeneity. These factors can
      contribute to a lack of agreement among related studies, limiting the utility of
      their aggregation. We show that it is feasible to carry out an automatic
      correction of individual datasets to reduce the effect of such 'latent variables'
      (without prior knowledge of the variables) in such a way that datasets addressing
      the same condition show better agreement once each is corrected. We build our
      approach on the method of surrogate variable analysis but we demonstrate that the
      original algorithm is unsuitable for the analysis of human tissue samples that
      are mixtures of different cell types. We propose a modification to SVA that is
      crucial to obtaining the improvement in agreement that we observe. We develop our
      method on a compendium of multiple sclerosis data and verify it on an independent
      compendium of Parkinson's disease datasets. In both cases, we show that our
      method is able to improve agreement across varying study designs, platforms, and
      tissues. This approach has the potential for wide applicability to any field
      where lack of inter-study agreement has been a concern. 

PMID- 24740472
TI  - A protein-based electrochemical biosensor for detection of tau protein, a
      neurodegenerative disease biomarker.
AB  - A protein-based electrochemical biosensor was developed for detection of tau
      protein aimed towards electrochemically sensing misfolding proteins. The
      electrochemical assay monitors tau-tau binding and misfolding during the early
      stage of tau oligomerization. Electrochemical impedance spectroscopy was used to
      detect the binding event between solution tau protein and immobilized tau protein
      (tau-Au), acting as a recognition element. The charge transfer resistance (Rct)
      of tau-Au was 2.9 +/- 0.6 kOmega. Subsequent tau binding to tau-Au decreased the
      Rct to 0.3 +/- 0.1 kOmega (90 +/- 3% decrease) upon formation of a tau-tau-Au
      interface. A linear relationship between the Rct and the solution tau
      concentration was observed from 0.2 to 1.0 MUM. The Rct decrease was attributed
      to an enhanced charge permeability of the tau-tau-Au surface to a redox probe
      [Fe(CN)6](3-/4-). The electrochemical and surface characterization data suggested
      conformational and electrostatic changes induced by tau-tau binding. The protein
      based electrochemical platform was highly selective for tau protein over bovine
      serum albumin and allowed for a rapid sample analysis. The protein-based
      interface was selective for a non-phosphorylated tau441 isoform over the paired
      helical filaments of tau, which were composed of phosphorylated and truncated tau
      isoforms. The electrochemical approach may find application in screening of the
      early onset of neurodegeneration and aggregation inhibitors. 

PMID- 24740473
TI  - The social brain, stress, and psychopathology.

PMID- 24740474
TI  - Noise-enhanced gel electrophoresis.
AB  - Macromolecules confined within a nanoporous matrix experience entropic trapping
      when their dimensions approach the average pore size, leading to emergence of
      anomalous transport behavior that can be beneficial in separation applications.
      But the ability to exploit these effects in practical settings (e.g.,
      electrophoretic separation of DNA) has been hindered by additional dispersion
      introduced as a consequence of the uncorrelated process by which the embedded
      macromolecules discretely hop from pore to pore. Here, we show how both the
      source and solution to these difficulties are intimately linked to the inherent
      dynamics of the underlying activated transport mechanism. By modulating the
      applied electric field at a frequency tuned to the characteristic activation
      timescale, a resonance condition can be established that synergistically combines
      accelerated mobility and reduced diffusion. This resonance effect can be
      precisely manipulated by adjusting the magnitude and period of the driving
      electric field, enabling enhanced separation performance and bi-directional
      transport of different-sized species to be achieved. Notably, these phenomena are
      readily accessible in ordinary hydrogels (as opposed to idealized nanomachined
      topologies) suggesting broad potential to apply them in a host of useful
      settings.

PMID- 24740475
TI  - The decreasing trend in hip fractures: response to Stevens & Rudd.

PMID- 24740477
TI  - Preliminary efficacy of prize-based contingency management to increase activity
      levels in healthy adults.
AB  - An estimated 30% of Americans meet the criteria for obesity. Effective, low-cost
      interventions to increase physical activity are needed to prevent and treat
      obesity. In this study, 11 healthy adults wore Fitbit accelerometers for 3 weeks.
      During the initial baseline, subjects earned prize draws for wearing the Fitbit.
      During intervention, percentile schedules were used to calculate individual prize
      draw criteria. The final week was a return to baseline. Four subjects increased
      step counts as a result of the intervention. A bout analysis of interresponse
      times revealed that subjects increased overall step counts by increasing daily
      minutes active and within-bout response rates and decreasing pauses between bouts
      of activity. Strategies to improve effectiveness are suggested, such as
      modification of reinforcement probability and amount and identification of the
      function of periods of inactivity. 

PMID- 24740476
TI  - Calcium and vitamin D intake maintained from preovariectomy independently affect
      calcium metabolism and bone properties in Sprague Dawley rats.
AB  - The interaction of habitual Ca and vitamin D intake from preovariectomy to 4
      months postovariectomy on bone and Ca metabolism was assessed. Higher Ca intake
      suppressed net bone turnover, and both nutrients independently benefitted
      trabecular structure. Habitual intake of adequate Ca and ~50 nmol/L vitamin D
      status is most beneficial. INTRODUCTION: Dietary strategies to benefit bone are
      typically tested prior to or after menopause but not through menopause
      transition. We investigated the interaction of Ca and vitamin D status on Ca
      absorption, bone remodeling, Ca kinetics, and bone strength as rats transitioned
      through estrogen deficiency. METHODS: Sprague Dawley rats were randomized at 8
      weeks to 0.2 or 1.0 % Ca and 50, 100, or 1,000 IU (1.25, 2.5, or 25 MUg) vitamin
      D/kg diet (2 * 3 factorial design) and ovariectomized at 12 weeks. Urinary (45)Ca
      excretion from deep-labeled bone was used to assess net bone turnover weekly. Ca
      kinetics was performed between 25 and 28 weeks. Rats were killed at 29 weeks.
      Femoral and tibiae structure (by MUCT), dynamic histomorphometry, and bone Ca
      content were assessed. RESULTS: Mean 25(OH)D for rats on the 50, 100, 1,000 IU
      vitamin D/kg diet were 32, 54, and 175 nmol/L, respectively. Higher Ca intake
      ameliorated net bone turnover, reduced fractional Ca absorption and bone
      resorption, and increased net Ca absorption. Tibial and femoral trabecular
      structures were enhanced independently by higher Ca and vitamin D intake. Tibial
      bone width and fracture resistance were enhanced by higher vitamin D intake.
      Dynamic histomorphometry in the tibia was not affected by either nutrient. A Ca *
      vitamin D interaction existed in femur length, tibial Ca content, and mass of the
      soft tissue/extracellular fluid compartment. CONCLUSIONS: Adequate Ca intake and
      serum 25(OH)D level of 50 nmol/L provided the most benefit for bone health,
      mostly through independent effects of Ca and vitamin D.

PMID- 24740478
TI  - Aqueous-solution route to zinc telluride films for application to CO2 reduction.
AB  - As a photocathode for CO2 reduction, zinc-blende zinc telluride (ZnTe) was
      directly formed on a Zn/ZnO nanowire substrate by a simple dissolution
      recrystallization mechanism without any surfactant. With the most negative
      conduction-band edge among p-type semiconductors, this new photocatalyst showed
      efficient and stable CO formation in photoelectrochemical CO2 reduction at -0.2-
      0.7 V versus RHE without a sacrificial reagent.

PMID- 24740479
TI  - Large-scale assessment of Mediterranean marine protected areas effects on fish
      assemblages.
AB  - Marine protected areas (MPAs) were acknowledged globally as effective tools to
      mitigate the threats to oceans caused by fishing. Several studies assessed the
      effectiveness of individual MPAs in protecting fish assemblages, but regional
      assessments of multiple MPAs are scarce. Moreover, empirical evidence on the role
      of MPAs in contrasting the propagation of non-indigenous-species (NIS) and
      thermophilic species (ThS) is missing. We simultaneously investigated here the
      role of MPAs in reversing the effects of overfishing and in limiting the spread
      of NIS and ThS. The Mediterranean Sea was selected as study area as it is a
      region where 1) MPAs are numerous, 2) fishing has affected species and
      ecosystems, and 3) the arrival of NIS and the northward expansion of ThS took
      place. Fish surveys were done in well-enforced no-take MPAs (HP), partially
      protected MPAs (IP) and fished areas (F) at 30 locations across the
      Mediterranean. Significantly higher fish biomass was found in HP compared to IP
      MPAs and F. Along a recovery trajectory from F to HP MPAs, IP were similar to F,
      showing that just well enforced MPAs triggers an effective recovery. Within HP
      MPAs, trophic structure of fish assemblages resembled a top-heavy biomass
      pyramid. Although the functional structure of fish assemblages was consistent
      among HP MPAs, species driving the recovery in HP MPAs differed among locations:
      this suggests that the recovery trajectories in HP MPAs are likely to be
      functionally similar (i.e., represented by predictable changes in trophic groups,
      especially fish predators), but the specific composition of the resulting
      assemblages may depend on local conditions. Our study did not show any effect of
      MPAs on NIS and ThS. These results may help provide more robust expectations, at
      proper regional scale, about the effects of new MPAs that may be established in
      the Mediterranean Sea and other ecoregions worldwide. 

PMID- 24740481
TI  - Nonlinear superchiral meta-surfaces: tuning chirality and disentangling non
      reciprocity at the nanoscale.
AB  - Circularly polarized light is incident on a nanostructured chiral meta-surface.
      In the nanostructured unit cells whose chirality matches that of light,
      superchiral light is forming and strong optical second harmonic generation can be
      observed. 

PMID- 24740480
TI  - Characterization of the effects of a polyunsaturated fatty acid (PUFA) on
      mitochondrial bioenergetics of chronologically aged yeast.
AB  - Increased membrane unsaturation has been associated with shorter longevity due to
      higher sensitivity to lipid peroxidation (LP) leading to enhanced mitochondrial
      dysfunction and ROS overproduction. However, the role of LP during aging has been
      put in doubt along with the participation of electron leak at the electron
      transport chain (ETC) in ROS generation in aged organisms. Thus, to test these
      hypothesis and gain further information about how minimizing LP preserves ETC
      function during aging, we studied the effects of alpha-linolenic acid (C18:3) on
      in situ mitochondrial ETC function, ROS production and viability of
      chronologically aged cells of S. cerevisiae, whose membranes are intrinsically
      resistant to LP due to the lack of PUFA. Increased sensitivity to LP was observed
      in cells cultured with C18:3 at 6 days of aging. This was associated with higher
      viability loss, dissipated membrane potential, impaired respiration and increased
      ROS generation, being these effects more evident at 28 days. However, at this
      point, lower sensitivity to LP was observed without changes in the membrane
      content of C18:3, suggesting the activation of a mechanism counteracting LP. The
      cells without C18:3 display better viability and mitochondrial functionality with
      lower ROS generation even at 28 days of aging and this was attributed to full
      preservation of complex III activity. These results indicate that the presence of
      PUFA in membranes enhances ETC dysfunction and electron leak and suggest that
      complex III is crucial to preserve membrane potential and to maintain a low rate
      of ROS production during aging.

PMID- 24740482
TI  - Microbleeds on susceptibility-weighted MRI in depressive and non-depressive
      patients after mild traumatic brain injury.
AB  - The aim of this study was to explore the relationship between abnormality on
      susceptibility-weighted imaging (SWI) and newly-developed depression after mild
      traumatic brain injury. The study registered 200 patients with closed TBI and
      normal finding at CT and conventional MRI. All patients underwent MRI including
      conventional MR sequences and SWI. The number and volume of microbleed lesions
      were semi-automatically outlined and manually counted. All patients were followed
      up with the Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-IV)
      within 1 year after TBI. The difference in microbleed lesions on SWI was compared
      between the depressive and non-depressive groups. The depressive group had a
      higher rate of abnormality on SWI than did the non-depressive group (p < 0.001).
      Among patients that had exhibited microbleed lesions, the number and volume of
      lesions were greater in the depressive group than the non-depressive group (both
      p < 0.001). These differences in numbers and volume of lesions were found only at
      the frontal, parietal and temporal lobes (all p < 0.001). Among patients that had
      exhibited microbleed lesions, the number and volume of lesions in other areas
      were not significantly different between the depressive and non-depressive groups
      (all p > 0.05). In conclusion, SWI was useful to identify the microbleed lesions
      after mild TBI. The distribution range and location of microbleed lesions were
      correlated with depression after TBI.

PMID- 24740484
TI  - Functional electrical stimulation for management of urinary incontinence in
      children with myelomeningocele: a randomized trial.
AB  - PURPOSE: To report the efficacy of transcutaneous functional electrical
      stimulation (FES) in children with refractory neuropathic urinary incontinence
      secondary to myelomeningocele (MMC). METHODS: Thirty children with history of MMC
      (12 girls and 18 boys, mean age 6.7 +/- 3.6 years) with refractory urinary
      incontinence were enrolled in this study. They were randomly allocated to
      treatment (FES, 15 children) and control (sham stimulation, 15 children) groups.
      All patients underwent urodynamic study (UDS) before and 6 months after FES
      considering detrusor leak point pressure (DLPP), mean maximal detrusor pressure,
      and mean maximal bladder capacity. Daily incontinence score, frequency of pad
      changing, and enuresis were also assessed before and 6 months after treatment. A
      15-course FES was performed for 15 min and 3 times per week. Children were
      followed for at least 6 months. RESULTS: Of UDS variables, DLPP increased
      significantly from 32 +/- 10.7 cmH2O before treatment to 55.6 +/- 24.9 cmH2O in
      treatment group after 6 months (P < 0.03). Daily incontinence score (range 0-3)
      improved significantly in treatment group from 2.7 +/- 0.4 before treatment to
      1.3 +/- 0.9 after treatment compared with sham stimulation group (P < 0.02).
      CONCLUSION: This type of electrical stimulation is a safe, noninvasive, and
      effective modality to improve urinary incontinence in myelomeningocele children
      and can be used at home.

PMID- 24740485
TI  - Traction force microscopy in physics and biology.
AB  - Adherent cells, crawling slugs, peeling paint, sessile liquid drops, bearings and
      many other living and non-living systems apply forces to solid substrates.
      Traction force microscopy (TFM) provides spatially-resolved measurements of
      interfacial forces through the quantification and analysis of the deformation of
      an elastic substrate. Although originally developed for adherent cells, TFM has
      no inherent size or force scale, and can be applied to a much broader range of
      mechanical systems across physics and biology. In this paper, we showcase the
      wide range of applicability of TFM, describe the theory, and provide experimental
      details and code so that experimentalists can rapidly adopt this powerful
      technique. 

PMID- 24740483
TI  - Re-visiting Hypersensitivity Reactions to Taxanes: A Comprehensive Review.
AB  - Taxanes (a class of chemotherapeutic agents) are an important cause of
      hypersensitivity reactions (HSRs) in cancer patients. During the last decade, the
      development of rapid drug desensitization has been key to allow patients with
      HSRs to taxanes to be safely re-treated although the mechanisms of these HSRs are
      not fully understood. Earlier studies suggested that solvents, such as Cremophor
      EL used to solubilize paclitaxel, were responsible for HSRs through complement
      activation, but recent findings have raised the possibility that some of these
      HSRs are IgE-mediated. Taxane skin testing, which identifies patients with an IgE
      mediated sensitivity, appears as a promising diagnostic and risk stratification
      tool in the management of patients with HSRs to taxanes. The management of
      patients following a HSR involves risk stratification and re-exposure could be
      performed either through rapid drug desensitization or graded challenge based on
      the severity of the initial HSR and the skin test result. Rapid drug
      desensitization has been shown to be an effective and safe method to re-introduce
      taxanes in hundreds of patients, including those with life-threatening HSRs.
      Patients with non-severe delayed skin HSRs may benefit from rapid drug
      desensitization since they may be at increased risk for an immediate HSR upon re
      exposure. This review focuses on the clinical presentation, diagnosis, and novel
      mechanisms of immediate HSRs to taxanes. A new management strategy for HSRs to
      taxanes based on skin testing and rapid drug desensitization is proposed.

PMID- 24740486
TI  - Systematic review and meta-analysis of laparoscopic versus open distal
      gastrectomy.
AB  - BACKGROUND: Laparoscopic distal gastrectomy has been increasingly utilized in the
      treatment of gastric adenocarcinoma. This study aims to compare the
      morbidity/mortality and postoperative outcomes of laparoscopic-assisted versus
      open distal gastrectomy since 2000. METHODS: A comprehensive search of MEDLINE
      and EMBASE was conducted including studies published between 2000 and present.
      RESULTS: Seventeen studies with a total of 7,109 distal gastrectomies (3,496 lap
      vs 3,613 open) were included. Across all studies, postoperative morbidity rates
      for laparoscopic gastrectomy were lower than that of open [median (range) 10 (0
      36) % vs 17 (0-43) %]. Meta-analysis of postoperative morbidity rates in
      prospective studies only yielded pooled odds ratio of 0.52 (95 % CI 0.33-0.81) (P
      = 0.004). In-hospital mortality rates were comparable between the two (range:
      laparoscopic 0-3.3 vs open 0-6.7 %). The long-term oncological outcomes of
      resection were difficult to analyze given variable reporting but appeared similar
      between the two. Meta-analysis of prospective studies showed that laparoscopic
      assisted distal gastrectomy was associated with significantly shorter hospital
      length of stay [standard mean difference (SMD) = -0.78 (95 % CI = -1.0 to 
      0.56)], comparable intraoperative bleeding [SMD = 0.64 (95 % CI = -1.3-0.0430) P
      = 0.066] and longer operative time compared to open gastrectomy [1.9 (95 % CI
      0.05-3.8) P = 0.045, with P < 0.001]. CONCLUSION: This study supports the use of
      laparoscopic-assisted distal gastrectomy for treatment of gastric adenocarcinoma
      with evidence of comparable, if not better, short-term postoperative parameters
      when compared to open distal gastrectomy. The long-term oncological outcomes
      appear similar but may require more evaluation.

PMID- 24740487
TI  - Brachytherapy in children with rhabdomyosarcomas of the nasolabial fold.
AB  - BACKGROUND: Rhabdomyosarcomas (RMS) of the nasolabial fold can be difficult to
      manage surgically due to functional and cosmetic limitations. Therefore,
      brachytherapy (BT) has been proposed to improve local control while limiting the
      volume of irradiation as well as the extent of the surgical excision. MATERIALS
      AND METHODS: Sixteen pediatric cases with RMS of the nasolabial fold treated from
      1971 to 2005 were retrospectively reviewed. RESULTS: Median follow-up was 4.4
      years (1.7-33). Half of the patients were male and their age at diagnosis ranged
      from 4 months to 13.5 years. Histological subtypes included 10 embryonal and 6
      alveolar RMS. Initial treatment consisted of induction multi-agent chemotherapy
      in all cases. In 12 patients, BT was combined with local excision (4 complete
      resections, 1 with macroscopic residual disease, and 7 with microscopic disease).
      Low dose-rate brachytherapy was performed in all cases according to the Paris
      system, using plastic catheters implanted per-operatively. The doses delivered
      ranged from 50 to 70 Gy, depending on chemotherapy response, and surgical margin
      status. 10 patients relapsed: 4 local, 6 regional, and 2 metastatic failures were
      reported. The median time to relapse was 6.5 months. At the time of analysis
      eight patients were alive and four had died. Four cases, under palliative care at
      last check-up, were lost to follow-up. CONCLUSION: BT provided an acceptable
      local control rate, but the poor regional control of these cases may suggest a
      need for more aggressive management of cervical regional lymph node regions in
      RMS of the nasolabial fold.

PMID- 24740488
TI  - Outlier detection method in GEEs.
AB  - The generalized estimating equations (GEEs) method has become quite useful in
      modeling correlated data. However, diagnostic tools to check that the selected
      final model fits the data as accurately as possible have not been explored
      intensively. In this paper, an outlier detection technique is developed based on
      the use of the "working" score test statistic to test an appropriate mean-shift
      model in the context of longitudinal studies based on GEEs. Through a simulation
      study it has been shown that this method correctly singled out the outlier when
      the data set had a known outlier. The method is applied to a set of data to
      illustrate the outlier detection procedure in GEEs. 

PMID- 24740489
TI  - Functional analysis and treatment of the diurnal bruxism of a 16-year-old girl
      with autism.
AB  - Bruxism is defined as the clenching and grinding of teeth. This study used a
      functional analysis to examine whether the bruxism of a 16-year-old girl with
      autism was maintained by automatic reinforcement or social consequences. A
      subsequent component analysis of the intervention package described by Barnoy,
      Najdowski, Tarbox, Wilke, and Nollet (2009) showed that a vocal reprimand (e.g.,
      "stop grinding") effectively reduced the participant's bruxism. Results were
      maintained across time, and effects extended to novel staff members. 

PMID- 24740490
TI  - Ligand influences on homoleptic Group 12 m-terphenyl complexes.
AB  - Three m-terphenyl ligands 2,6-Ar2C6H3(-) [Ar = 2,6-Me2C6H3 (2,6-Xyl); 3,5-Me2C6H3
      (3,5-Xyl); 2,3,4,5,6-Me5C6 (Pmp)] have been used to stabilise three series of two
      coordinate Group 12 diaryl complexes; (2,6-Ar2C6H3)2M [M = Zn, Cd, Hg, Ar = 2,6
      Xyl 1-3, 3,5-Xyl 4-6, Pmp 7-9], where differing steric demands on the metal
      centres are imparted. These are the first homoleptic d-block complexes featuring
      any of these ligands. Complexes 1-9 have been characterised in solution and the
      solid state; the analysis of structural changes produced by differences in ligand
      properties is reported. In particular, complexes 4-6 show smaller C-M-C bond
      angles and contain secondary ligand interactions that are not seen in the
      analogous complexes 1-3 and 7-9.

PMID- 24740491
TI  - Neuroimaging evidence for a role of neural social stress processing in ethnic
      minority-associated environmental risk.
AB  - IMPORTANCE: Relative risk for the brain disorder schizophrenia is more than
      doubled in ethnic minorities, an effect that is evident across countries and
      linked to socially relevant cues such as skin color, making ethnic minority
      status a well-established social environmental risk factor. Pathoepidemiological
      models propose a role for chronic social stress and perceived discrimination for
      mental health risk in ethnic minorities, but the neurobiology is unexplored.
      OBJECTIVE: To study neural social stress processing, using functional magnetic
      resonance imaging, and associations with perceived discrimination in ethnic
      minority individuals. DESIGN, SETTING, AND PARTICIPANTS: Cross-sectional design
      in a university setting using 3 validated paradigms to challenge neural social
      stress processing and, to probe for specificity, emotional and cognitive brain
      functions. Healthy participants included those with German lineage (n = 40) and
      those of ethnic minority (n = 40) from different ethnic backgrounds matched for
      sociodemographic, psychological, and task performance characteristics. Control
      comparisons examined stress processing with matched ethnic background of
      investigators (23 Turkish vs 23 German participants) and basic emotional and
      cognitive tasks (24 Turkish vs 24 German participants). MAIN OUTCOMES AND
      MEASURES: Blood oxygenation level-dependent response, functional connectivity,
      and psychological and physiological measures. RESULTS: There were significant
      increases in heart rate (P < .001), subjective emotional response (self-related
      emotions, P < .001; subjective anxiety, P = .006), and salivary cortisol level (P
      = .004) during functional magnetic resonance imaging stress induction. Ethnic
      minority individuals had significantly higher perceived chronic stress levels (P
      = .02) as well as increased activation (family-wise error-corrected [FWE] P =
      .005, region of interest corrected) and increased functional connectivity (PFWE =
      .01, region of interest corrected) of perigenual anterior cingulate cortex (ACC).
      The effects were specific to stress and not explained by a social distance
      effect. Ethnic minority individuals had significant correlations between
      perceived group discrimination and activation in perigenual ACC (PFWE = .001,
      region of interest corrected) and ventral striatum (PFWE = .02, whole brain
      corrected) and mediation of the relationship between perceived discrimination and
      perigenual ACC-dorsal ACC connectivity by chronic stress (P < .05). CONCLUSIONS
      AND RELEVANCE: Epidemiologists proposed a causal role of social-evaluative
      stress, but the neural processes that could mediate this susceptibility effect
      were unknown. Our data demonstrate the potential of investigating associations
      from epidemiology with neuroimaging, suggest brain effects of social
      marginalization, and highlight a neural system in which environmental and genetic
      risk factors for mental illness may converge.

PMID- 24740492
TI  - Graphene quantum dots enhanced electrochemiluminescence of cadmium sulfide
      nanocrystals for ultrasensitive determination of pentachlorophenol.
AB  - An ultrasensitive electrochemiluminescence (ECL) sensor based on the ECL
      amplifying behavior of the graphene quantum dots-CdS nanocrystals (GQDs-CdS NCs)
      was constructed for the detection of pentachlorophenol (PCP). Because of the
      presence of doped GQDs, the resulting GQDs-CdS NCs exhibited 5-fold enhanced ECL
      intensity than pure CdS NCs with the ECL onset potential positively shifted by 80
      mV. Furthermore, based on the effective inhibition of the ECL response of GQDs
      CdS NCs film by PCP, a simple method for ultrasensitive determination of PCP was
      devised, which showed a wide linear range of 0.01-500 ng mL(-1) and a low
      detection limit of 3 pg mL(-1) (S/N = 3) with good stability, reproducibility and
      applicability for PCP detection in real water samples. Thus, it can be expected
      that GQDs-based composites with excellent performance may play a more important
      role in pesticide determination. 

PMID- 24740493
TI  - Characterization of neurosteroid effects on hyperpolarizing current at
      alpha4beta2delta GABAA receptors.
AB  - RATIONALE: The neurosteroid 3alpha,5beta-THP (3alpha-OH-5beta-pregnan-20-one,
      pregnanolone) is a modulator of the GABAA receptor (GABAR), with alpha4beta2delta
      GABARs the most sensitive. However, the effects of 3alpha,5beta-THP at
      alpha4beta2delta are polarity-dependent: 3alpha,5beta-THP potentiates
      depolarizing current, as has been widely reported, but decreases hyperpolarizing
      current by accelerating desensitization. OBJECTIVES: The present study further
      characterized 3alpha,5beta-THP inhibition of hyperpolarizing current at this
      receptor and compared effects of other related steroids at alpha4beta2delta
      GABARs. METHODS: alpha4beta2delta GABARs were expressed in HEK-293 cells, and
      agonist-gated current recorded with whole cell voltage-clamp techniques using a
      theta tube to rapidly apply agonist before and after application of
      neurosteroids. RESULTS: The GABA-modulatory steroids (30 nM) 3alpha,5alpha-THP
      (3alpha-OH-5alpha-pregnan-20-one, allopregnanolone) and THDOC (3alpha,21
      dihydroxy-5alpha-pregnan-20-one) inhibited hyperpolarizing GABA (10 MUM)-gated
      current at alpha4beta2delta GABARs similar to 3alpha,5beta-THP, while the
      inactive 3beta,5beta-THP isomer had no effect. Greater inhibition was seen for
      current gated by the high efficacy agonist gaboxadol (THIP, 100 MUM) than for
      GABA (0.1-1000 MUM), consistent with an effect of 3alpha,5beta-THP on
      desensitization. Inhibitory effects of the steroid were not seen under low [Cl(
      )] conditions or in the presence of calphostin C (500 nM), an inhibitor of
      protein kinase C. Chimeras swapping the IL (intracellular loop) of alpha4 with
      alpha1, when expressed with beta2 and delta, produced receptors
      (alpha[414]beta2delta) which were not inhibited by 3alpha,5beta-THP when GABA
      gated current was hyperpolarizing, while alpha[141]beta2delta exhibited steroid
      induced polarity-dependent modulation. CONCLUSIONS: These findings suggest that
      numerous neurosteroids exhibit polarity-dependent effects at alpha4beta2delta
      GABARs, which are dependent upon protein kinase C and the IL of alpha4.

PMID- 24740495
TI  - Characterization of Adults With a Self-Diagnosis of Nonceliac Gluten Sensitivity.
AB  - Background: Nonceliac gluten sensitivity (NCGS), occurring in patients without
      celiac disease yet whose gastrointestinal symptoms improve on a gluten-free diet
      (GFD), is largely a self-reported diagnosis and would appear to be very common.
      The aims of this study were to characterize patients who believe they have NCGS.
      Materials and Methods: Advertising was directed toward adults who believed they
      had NCGS and were willing to participate in a clinical trial. Respondents were
      asked to complete a questionnaire about symptoms, diet, and celiac investigation.
      Results: Of 248 respondents, 147 completed the survey. Mean age was 43.5 years,
      and 130 were women. Seventy-two percent did not meet the description of NCGS due
      to inadequate exclusion of celiac disease (62%), uncontrolled symptoms despite
      gluten restriction (24%), and not following a GFD (27%), alone or in combination.
      The GFD was self-initiated in 44% of respondents; in other respondents it was
      prescribed by alternative health professionals (21%), dietitians (19%), and
      general practitioners (16%). No celiac investigations had been performed in 15%
      of respondents. Of 75 respondents who had duodenal biopsies, 29% had no or
      inadequate gluten intake at the time of endoscopy. Inadequate celiac
      investigation was common if the GFD was initiated by self (69%), alternative
      health professionals (70%), general practitioners (46%), or dietitians (43%). In
      40 respondents who fulfilled the criteria for NCGS, their knowledge of and
      adherence to the GFD were excellent, and 65% identified other food intolerances.
      Conclusions: Just over 1 in 4 respondents self-reporting as NCGS fulfill criteria
      for its diagnosis. Initiation of a GFD without adequate exclusion of celiac
      disease is common. In 1 of 4 respondents, symptoms are poorly controlled despite
      gluten avoidance.

PMID- 24740496
TI  - Low energy intake during the first week in an emergency intensive care unit is
      associated with reduced duration of mechanical ventilation in critically ill,
      underweight patients: a single-center retrospective chart review.
AB  - BACKGROUND: Although nutrition support is essential in intensive care units,
      optimal energy intake remains unclear. Here, we assessed the influence of energy
      intake on outcomes of critically ill, underweight patients. METHODS: A
      retrospective chart review was conducted in patients with body mass index (BMI)
      of <20.0 kg/m(2) in an emergency intensive care unit (EICU). Patients were
      categorized into 4 groups by initial Sequential Organ Failure Assessment score (I
      SOFA) and average daily energy intake during the first week: group M-1, I-SOFA
      <=8 and <16 kcal/kg/d; group M-2, I-SOFA <=8 and >=16 kcal/kg/d; group S-1, I
      SOFA >8 and <16 kcal/kg/d; and group S-2, I-SOFA >8 and >=16 kcal/kg/d. RESULTS:
      The study included 51 patients with a median age of 69 years. No significant
      differences were noted in all-cause mortality and length of stay in the EICU and
      hospital between groups M-1 and M-2 or groups S-1 and S-2. The mechanical
      ventilation duration (MVD) was significantly shorter in group M-1 than M-2 (2.7
      [1.0-5.7] vs 9.2 [4.2-17.4] days; P = .040) and in group S-1 than S-2 (3.1 [0.7
      6.0] vs 8.8 [6.1-23.1] days; P = .006). The number of patients who underwent
      tracheostomy in hospital was significantly lower in group S-1 than in S-2 (20% vs
      32%; P = .002). Multivariable analyses to adjust for confounders revealed that
      average energy intake during the first week in EICU was a significant factor
      independently associated with MVD but not with the requirement of tracheostomy.
      CONCLUSION: Reduced energy intake during the first week in EICU was associated
      with a reduced MVD in clinically ill patients with BMI <20.0 kg/m(2).

PMID- 24740494
TI  - Role of the D1 receptor for the dopamine agonist-induced one-trial behavioral
      sensitization of preweanling rats.
AB  - RATIONALE: The neural mechanisms mediating the ontogeny of behavioral
      sensitization are poorly understood. OBJECTIVE: The purpose of the present study
      was to determine the role of the D1 receptor for the induction of dopamine
      agonist-induced behavioral sensitization during the preweanling period. METHODS:
      In the first experiment, the early ontogeny of R-propylnorapomorphine (NPA)
      induced behavioral sensitization was examined by pretreating male and female rats
      with saline or NPA (0.5, 1, or 2 mg/kg, intraperitoneally (IP)) before placement
      in activity chambers on postnatal day (PD) 12, 16, 20, or 24. One day later, rats
      were tested with lower doses of NPA and the occurrence of locomotor sensitization
      was determined. In subsequent experiments, rats were injected with saline or the
      D1 receptor antagonist SCH23390 (0.1, 0.5, 1, or 5 mg/kg, IP) 0, 15, 30, or 60
      min before cocaine, methamphetamine (METH), or NPA pretreatment. The next day,
      rats were tested with the same dopamine agonist again and sensitized responding
      was assessed. RESULTS: NPA produced one-trial behavioral sensitization at all
      ages tested. In preweanling rats, SCH23390, regardless of dose, was ineffective
      at preventing the induction of cocaine-, METH-, or NPA-induced one-trial
      behavioral sensitization. CONCLUSIONS: The present results are in partial
      contrast to adult rodent studies, in which SCH23390 blocks the induction of METH-
      and apomorphine-induced behavioral sensitization, but not cocaine sensitization.
      When these findings are considered together, it appears that D1 receptor
      stimulation is not necessary for the induction of behavioral sensitization during
      the preweanling period, although D1 receptors may play a more important role in
      adulthood.

PMID- 24740497
TI  - The role of complementary and alternative medicine for pancreatic disorders.

PMID- 24740498
TI  - Nutrition algorithms and bedside nutrient delivery practices in pediatric
      intensive care units: an international multicenter cohort study.
AB  - BACKGROUND: Enteral nutrition (EN) delivery is associated with improved outcomes
      in critically ill patients. We aimed to describe EN practices, including details
      of algorithms and individual bedside practices, in pediatric intensive care units
      (PICUs). METHODS: Available EN algorithm details from 31 international PICUs were
      obtained. Daily nutrient intake data from 524 mechanically ventilated patients, 1
      month to 18 years old, were prospectively documented, including EN delivery,
      adjunct therapies, and energy prescription. Practices associated with higher
      percentage adequacy of EN delivery were determined by regression analysis.
      RESULTS: Nine EN algorithms were available. All algorithms defined advancement
      and EN intolerance; 7 of 9 defined intolerance by gastric residual volume; 3 of 9
      recommended nutrition screening and fasting guidelines. Few elements were in
      agreement with the American Society for Parenteral and Enteral Nutrition and the
      European Society of Paediatric Gastroenterology, Hepatology, and Nutrition
      guidelines. Of the 341 patients who received EN exclusively 32.9% received
      >=66.6% of prescribed energy on day 7. Percentage adequacy of EN delivered was
      inversely associated with days to EN initiation (-8.92; P < .001) and hours per
      EN interruption (-1.65; P = .001) and was not associated with the use of
      algorithms, promotility agents, or postpyloric feeding. CONCLUSIONS: A minority
      of PICUs employ EN algorithms; recommendations were variable and not in agreement
      with national guidelines. Optimal EN delivery was achieved in less than one-third
      of our cohort. EN adjunct therapies were not associated with increased EN
      delivery. Studies aimed at promoting early EN and decreasing interruptions may
      optimize energy delivery in the PICU.

PMID- 24740499
TI  - Electrolyte system for fast preparative focusing in wide pH range based on
      bidirectional isotachophoresis.
AB  - In this paper, we suggest new electrolyte system for fast preparative
      electrofocusing in wide pH range. It is based on bidirectional ITP with multiple
      counterions and spacers created by commercially available defined simple buffers.
      The migration course of proposed focusing model can be simulated in advance by
      using separation conditions and electrolyte components that are consequently
      applied during the experiments. The suggested electrolyte system allows high
      current densities at the initial stages of focusing without danger of local
      overheating, which strongly reduces the time needed for analysis completion. The
      performance of the electrolyte system is demonstrated by the focusing of
      synthetic colored low molecular weight indicators and proteins in the
      arrangements with both linear narrow strip and nonwoven fabric sheet with
      continuous flow. 

PMID- 24740500
TI  - The nuclear receptor Nr4a1 mediates anti-inflammatory effects of apoptotic cells.
AB  - Uptake of apoptotic cells (ACs) by macrophages ensures the nonimmunogenic
      clearance of dying cells, as well as the maintenance of self-tolerance to AC
      derived autoantigens. Upon ingestion, ACs exert an inhibitory influence on the
      inflammatory signaling within the phagocyte. However, the molecular signals that
      mediate these immune-modulatory properties of ACs are incompletely understood. In
      this article, we show that the phagocytosis of apoptotic thymocytes was enhanced
      in tissue-resident macrophages where this process resulted in the inhibition of
      NF-kappaB signaling and repression of inflammatory cytokines, such as IL-12. In
      parallel, ACs induced a robust expression of a panel of immediate early genes,
      which included the Nr4a subfamily of nuclear receptors. Notably, deletion of
      Nr4a1 interfered with the anti-inflammatory effects of ACs in macrophages and
      restored both NF-kappaB signaling and IL-12 expression. Accordingly, Nr4a1
      mediated the anti-inflammatory properties of ACs in vivo and was required for
      maintenance of self-tolerance in the murine model of pristane-induced lupus.
      Thus, our data point toward a key role for Nr4a1 as regulator of the immune
      response to ACs and of the maintenance of tolerance to "dying self." 

PMID- 24740501
TI  - Dendritic cell-mediated immune humanization of mice: implications for allogeneic
      and xenogeneic stem cell transplantation.
AB  - De novo regeneration of immunity is a major problem after allogeneic
      hematopoietic stem cell transplantation (HCT). HCT modeling in severely
      compromised immune-deficient animals transplanted with human stem cells is
      currently limited because of incomplete maturation of lymphocytes and scarce
      adaptive responses. Dendritic cells (DC) are pivotal for the organization of
      lymph nodes and activation of naive T and B cells. Human DC function after HCT
      could be augmented with adoptively transferred donor-derived DC. In this study,
      we demonstrate that adoptive transfer of long-lived human DC coexpressing high
      levels of human IFN-alpha, human GM-CSF, and a clinically relevant Ag (CMV pp65
      protein) promoted human lymphatic remodeling in immune-deficient NOD.Rag1(-/-).IL
      2rgamma(-/-) mice transplanted with human CD34(+) cells. After immunization,
      draining lymph nodes became replenished with terminally differentiated human
      follicular Th cells, plasma B cells, and memory helper and cytotoxic T cells.
      Human Igs against pp65 were detectable in plasma, demonstrating IgG class-switch
      recombination. Human T cells recovered from mice showed functional reactivity
      against pp65. Adoptive immunotherapy with engineered DC provides a novel strategy
      for de novo immune reconstitution after human HCT and a practical and effective
      tool for studying human lymphatic regeneration in vivo in immune deficient
      xenograft hosts. 

PMID- 24740502
TI  - Cutting edge: NKG2C(hi)CD57+ NK cells respond specifically to acute infection
      with cytomegalovirus and not Epstein-Barr virus.
AB  - CMV induces the expansion of a unique subset of human NK cells expressing high
      levels of the activating CD94-NKG2C receptor that persist after control of the
      infection. We investigated whether this subset is CMV specific or is also
      responsive to acute infection with EBV. We describe a longitudinal study of CMV(
      ) and CMV(+) students who were acutely infected with EBV. The NKG2C(hi) NK subset
      was not expanded by EBV infection. However, EBV infection caused a decrease in
      the absolute number of immature CD56(bright)CD16(-) NK cells in the blood and, in
      CMV(+) individuals, induced an increased frequency of mature
      CD56(dim)NKG2A(+)CD57(+) NK cells in the blood that persisted into latency. These
      results provide further evidence that NKG2C(+) NK cells are CMV specific and
      suggest that EBV infection alters the repertoire of NK cells in the blood. 

PMID- 24740503
TI  - Protection from intestinal inflammation by bacterial exopolysaccharides.
AB  - Host inflammatory responses against pathogenic organisms can be abrogated by
      commensals; however, the molecular mechanisms by which pathogenesis is prevented
      are still poorly understood. Previous studies demonstrated that administration of
      a single dose of Bacillus subtilis prevented disease and inflammation by the
      enteric mouse pathogen Citrobacter rodentium, which causes disease similar to the
      human pathogen enteropathogenic Escherichia coli. No protection was observed when
      an exopolysaccharide (EPS)-deficient mutant of B. subtilis was used, suggesting
      that EPS are the protective factor. In this study, we isolated and characterized
      EPS and showed that they also prevent C. rodentium-associated intestinal disease
      after a single injection. Protection is TLR4 dependent because EPS-treated TLR4
      knockout mice developed disease. Furthermore, protection could be conveyed to
      wild-type mice by adoptive transfer of macrophage-rich peritoneal cells from EPS
      treated mice. We found that EPS specifically bind peritoneal macrophages, and
      because mice lacking MyD88 signaling in myeloid cells were not protected by EPS,
      we conclude that bacterial EPS prevent colitis in a TLR4-dependent manner that
      requires myeloid cells. These studies provide a simple means of preventing
      intestinal inflammation caused by enteric pathogens. 

PMID- 24740504
TI  - Release of cystic fibrosis airway inflammatory markers from Pseudomonas
      aeruginosa-stimulated human neutrophils involves NADPH oxidase-dependent
      extracellular DNA trap formation.
AB  - Cystic fibrosis (CF) airways are characterized by bacterial infections, excess
      mucus production, and robust neutrophil recruitment. The main CF airway pathogen
      is Pseudomonas aeruginosa. Neutrophils are not capable of clearing the infection.
      Neutrophil primary granule components, myeloperoxidase (MPO) and human neutrophil
      elastase (HNE), are inflammatory markers in CF airways, and their increased
      levels are associated with poor lung function. Identifying the mechanism of MPO
      and HNE release from neutrophils is of high clinical relevance for CF. In this
      article, we show that human neutrophils release large amounts of neutrophil
      extracellular traps (NETs) in the presence of P. aeruginosa. Bacteria are
      entangled in NETs and colocalize with extracellular DNA. MPO, HNE, and
      citrullinated histone H4 are all associated with DNA in Pseudomonas-triggered
      NETs. Both laboratory standard strains and CF isolates of P. aeruginosa induce
      DNA, MPO, and HNE release from human neutrophils. The increase in peroxidase
      activity of neutrophil supernatants after Pseudomonas exposure indicates that
      enzymatically active MPO is released. P. aeruginosa induces a robust respiratory
      burst in neutrophils that is required for extracellular DNA release. Inhibition
      of the cytoskeleton prevents Pseudomonas-initiated superoxide production and DNA
      release. NADPH oxidase inhibition suppresses Pseudomonas-induced release of
      active MPO and HNE. Blocking MEK/ERK signaling results in only minimal inhibition
      of DNA release induced by Pseudomonas. Our data describe in vitro details of DNA,
      MPO, and HNE release from neutrophils activated by P. aeruginosa. We propose that
      Pseudomonas-induced NET formation is an important mechanism contributing to
      inflammatory conditions characteristic of CF airways. 

PMID- 24740505
TI  - TLR3-responsive, XCR1+, CD141(BDCA-3)+/CD8alpha+-equivalent dendritic cells
      uncovered in healthy and simian immunodeficiency virus-infected rhesus macaques.
AB  - In mice, CD8alpha(+) myeloid dendritic cells (mDC) optimally cross-present Ags to
      CD8(+) T cells and respond strongly to TLR3 ligands. Although equivalent DC have
      been identified by comparative genomic analysis and functional studies in humans
      as XCR1(+)CD141 (BDCA-3)(+)Clec9A(+)cell adhesion molecule 1(+) mDC, and in sheep
      as CD26(+) mDC, these cells remained elusive in nonhuman primates. To remedy this
      situation, we delineated precisely DC and monocyte populations by 12-color flow
      cytometry and transcriptomic analyses in healthy rhesus macaques. We identified a
      new mDC population, with strong phenotypic and transcriptional homology to human
      CD141(+) and murine CD8alpha(+) mDC, including XCR1 membrane expression as a
      conserved specific marker. In contrast, high CD11c expression was not
      characteristic of mDC in macaques, but of CD16(+) monocytes. Like their human and
      murine homologs, simian XCR1(+) mDC had much stronger responses to TLR3
      stimulation than other myeloid cells. The importance of this new mDC population
      was tested in SIV(mac251) infection, the most relevant animal model for
      pathogenic HIV-1 infection and vaccination. This population increased sharply and
      transiently during acute infection, but was reduced in blood and spleen during
      advanced disease. The identification of XCR1(+) mDC in rhesus macaques opens new
      avenues for future preclinical vaccinal studies and highlights XCR1 as a prime
      candidate for targeted vaccine delivery.

PMID- 24740507
TI  - Cutting edge: Salivary gland NK cells develop independently of Nfil3 in steady
      state.
AB  - Nfil3 is viewed as an obligate transcription factor for NK cell development.
      However, mouse CMV (MCMV) infection recently was shown to bypass the requirement
      for Nfil3 by inducing the appearance of NK cells that express the MCMV-specific
      receptor Ly49H. Thus, signals transmitted by Ly49H and proinflammatory cytokines
      are sufficient to promote NK cell differentiation in the absence of Nfil3. In
      this study, we report that salivary gland (SG) NK cells develop in an Nfil3
      independent fashion in the steady-state in the absence of MCMV or any infection.
      Moreover, we show that SG NK cells have an integrin profile reminiscent of tissue
      resident lymphocytes and express TRAIL for killing target cells. These results
      demonstrate that SG NK cells, although related to conventional NK cells, are a
      distinct subset of innate lymphoid cells that deviates from the conventional
      developmental pathway, perhaps under the influence of tissue-specific factors. 

PMID- 24740506
TI  - Integrin-mediated interactions between B cells and follicular dendritic cells
      influence germinal center B cell fitness.
AB  - Integrin-ligand interactions between germinal center (GC) B cells and Ag
      presenting follicular dendritic cells (FDCs) have been suggested to play central
      roles during GC responses, but their in vivo requirement has not been directly
      tested. In this study, we show that, whereas integrins alphaLbeta2 and
      alpha4beta1 are highly expressed and functional on mouse GC B cells, removal of
      single integrins or their ligands had little effect on B cell participation in
      the GC response. Combined beta2 integrin deficiency and alpha4 integrin blockade
      also did not affect the GC response against a particulate Ag. However, the
      combined integrin deficiency did cause B cells to be outcompeted in splenic GC
      responses against a soluble protein Ag and in mesenteric lymph node GC responses
      against gut-derived Ags. Similar findings were made for beta2-deficient B cells
      in mice lacking VCAM1 on FDCs. The reduced fitness of the GC B cells did not
      appear to be due to decreased Ag acquisition, proliferation rates, or pAKT
      levels. In summary, our findings provide evidence that alphaLbeta2 and
      alpha4beta1 play overlapping and context-dependent roles in supporting
      interactions with FDCs that can augment the fitness of responding GC B cells. We
      also find that mouse GC B cells upregulate alphavbeta3 and adhere to vitronectin
      and milk-fat globule epidermal growth factor VIII protein. Integrin beta3
      deficient B cells contributed in a slightly exaggerated manner to GC responses,
      suggesting this integrin has a regulatory function in GC B cells. 

PMID- 24740508
TI  - Existence of conventional dendritic cells in Gallus gallus revealed by
      comparative gene expression profiling.
AB  - The existence of conventional dendritic cells (cDCs) has not yet been
      demonstrated outside mammals. In this article, we identified bona fide cDCs in
      chicken spleen. Comparative profiling of global and of immune response gene
      expression, morphology, and T cell activation properties show that cDCs and
      macrophages (MPs) exist as distinct mononuclear phagocytes in the chicken,
      resembling their human and mouse cell counterparts. With computational analysis,
      core gene expression signatures for cDCs, MPs, and T and B cells across the
      chicken, human, and mouse were established, which will facilitate the
      identification of these subsets in other vertebrates. Overall, this study, by
      extending the newly uncovered cDC and MP paradigm to the chicken, suggests that
      these two phagocyte lineages were already in place in the common ancestor of
      reptiles (including birds) and mammals in evolution. It opens avenues for the
      design of new vaccines and nutraceuticals that are mandatory for the sustained
      supply of poultry products in the expanding human population. 

PMID- 24740509
TI  - Tissue-resident exhausted effector memory CD8+ T cells accumulate in the retina
      during chronic experimental autoimmune uveoretinitis.
AB  - Experimental autoimmune uveoretinitis is a model for noninfectious posterior
      segment intraocular inflammation in humans. Although this disease is CD4(+) T
      cell dependent, in the persistent phase of disease CD8(+) T cells accumulate. We
      show that these are effector memory CD8(+) T cells that differ from their splenic
      counterparts with respect to surface expression of CD69, CD103, and Ly6C. These
      retinal effector memory CD8(+) T cells have limited cytotoxic effector function,
      are impaired in their ability to proliferate in response to Ag-specific
      stimulation, and upregulate programmed death 1 receptor. Treatment with
      fingolimod (FTY720) during the late phase of disease revealed that retinal CD8(+)
      T cells were tissue resident. Despite signs of exhaustion, these cells were
      functional, as their depletion resulted in an expansion of retinal CD4(+) T cells
      and CD11b(+) macrophages. These results demonstrate that, during chronic
      autoimmune inflammation, exhausted CD8(+) T cells become established in the local
      tissue. They are phenotypically distinct from peripheral CD8(+) T cells and
      provide local signals within the tissue by expression of inhibitory receptors
      such as programmed death 1 that limit persistent inflammation. 

PMID- 24740511
TI  - Enantioselective organo-photocatalysis mediated by atropisomeric thiourea
      derivatives.
AB  - Can photocatalysis be performed without electron or energy transfer? To address
      this, organo-photocatalysts that are based on atropisomeric thioureas and display
      lower excited-state energies than the reactive substrates have been developed.
      These photocatalysts were found to be efficient in promoting the [2+2]
      photocycloaddition of 4-alkenyl-substituted coumarins, which led to the
      corresponding products with high enantioselectivity (77-96% ee) at low catalyst
      loading (1-10 mol%). The photocatalytic cycle proceeds by energy sharing via the
      formation of both static and dynamic complexes (exciplex formation), which is
      aided by hydrogen bonding.

PMID- 24740510
TI  - Functional avidity and IL-2/perforin production is linked to the emergence of
      mutations within HLA-B*5701-restricted epitopes and HIV-1 disease progression.
AB  - Viral escape from HIV-1-specific CD8(+) T cells has been demonstrated in numerous
      studies previously. However, the qualitative features driving the emergence of
      mutations within epitopes are still unclear. In this study, we aimed to
      distinguish whether specific functional characteristics of HLA-B*5701-restricted
      CD8(+) T cells influence the emergence of mutations in high-risk progressors
      (HRPs) versus low-risk progressors (LRPs). Single-genome sequencing was performed
      to detect viral mutations (variants) within seven HLA-B*5701-restricted epitopes
      in Gag (n = 4) and Nef (n = 3) in six untreated HLA-B*5701 subjects followed from
      early infection up to 7 y. Several well-characterized effector markers (IFN
      gamma, IL-2, MIP-1beta, TNF, CD107a, and perforin) were identified by flow
      cytometry following autologous (initial and emerging variant/s) epitope
      stimulations. This study demonstrates that specific functional attributes may
      facilitate the outgrowth of mutations within HLA-B*5701-restricted epitopes. A
      significantly lower fraction of IL-2-producing cells and a decrease in functional
      avidity and polyfunctional sensitivity were evident in emerging epitope variants
      compared with the initial autologous epitopes. Interestingly, the HRPs mainly
      drove these differences, whereas the LRPs maintained a directed and maintained
      functional response against emerging epitope variants. In addition, LRPs induced
      improved cell-cycle progression and perforin upregulation after autologous and
      emerging epitope variant stimulations in contrast to HRPs. The maintained
      quantitative and qualitative features of the CD8(+) T cell responses in LRPs
      toward emerging epitope variants provide insights into why HLA-B*5701 subjects
      have different risks of HIV-1 disease progression. 

PMID- 24740513
TI  - Increased risk of stroke among patients with ulcerative colitis: a population
      based matched cohort study.
AB  - BACKGROUND: The risk of venous thromboembolism (VTE) and the development of
      atherosclerosis are increased in patients with inflammatory bowel disease (IBD).
      Ulcerative colitis (UC) is one type of IBD; however, there is controversy in the
      literature regarding the association between UC and stroke. The present cohort
      study estimated the risk of subsequent stroke among UC patients compared with
      that among matched comparison subjects drawn from a population-based data set in
      Taiwan. METHODS: This investigation analyzed administrative claims data sourced
      from the Taiwan National Health Insurance Database. Our study consisted of a
      study cohort comprising 516 UC patients and a comparison cohort of 2,579 subjects
      without IBD. Cox proportional hazards regressions were performed to estimate the
      risk of subsequent stroke during the follow-up period. We also conducted
      additional analyses investigating the risk of subsequent stroke 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 UC was 2.045 (95 % confidence interval (CI) = 1.374
      3.043) than that among comparison subjects. While we did not detect an
      association between stroke and UC among patients aged 30-40 or 40-50 years, we
      did detect increased risks for stroke among UC patients aged over 50 years (HR =
      2.045). We also found the association to remain significant for both men (HR =
      2.153) and women (HR = 2.750). CONCLUSIONS: This study detected an increased HR
      for subsequent stroke among Taiwanese UC patients hen compared to that among
      matched comparison patients without IBD.

PMID- 24740514
TI  - Stimulation of the sphenopalatine ganglion in intractable cluster headache:
      expert consensus on patient selection and standards of care.
AB  - CONTEXT AND OVERVIEW: Chronic cluster headache (CCH) is a debilitating headache
      disorder with a significant impairment of the patients' lives. Within the past
      decade, various invasive neuromodulatory approaches have been proposed for the
      treatment of CCH refractory to standard preventive drug, but only very few
      randomized controlled studies exist in the field of neuromodulation for the
      treatment of drug-refractory headaches. Based on the prominent role of the
      cranial parasympathetic system in acute cluster headache attacks, high-frequency
      sphenopalatine ganglion (SPG) stimulation has been shown to abort ongoing attacks
      in some patients in a first small study. As preventive effects of SPG-stimulation
      have been suggested and the rate of long-term side effects was moderate, SPG
      stimulation appears to be a promising new treatment strategy. AIMS AND
      CONCLUSION: As SPG stimulation is effective in some patients and the first
      commercially available CE-marked SPG neurostimulator system has been introduced
      for cluster headache, patient selection and care should be standardized to ensure
      maximal efficacy and safety. As only limited data have been published on SPG
      stimulation, standards of care based on expert consensus are proposed to ensure
      homogeneous patient selection and treatment across international headache
      centres. Given that SPG stimulation is still a novel approach, all expert-based
      consensus on patient selection and standards of care should be re-reviewed when
      more long-term data are available.

PMID- 24740515
TI  - Aura status: a not so frequent aura.
AB  - BACKGROUND: Migraine aura status is a variety of migraine aura with unvalidated
      research criteria. AIM AND METHODS: We conducted a systematic review of published
      cases and a retrospective analysis of 500 cases of migraine with aura to evaluate
      the applicability and clinical features of ICHD-III beta criteria, compared to a
      more liberal definition for its diagnosis: >=3 aura episodes for up to three
      consecutive days. RESULTS: Many publications under this title correspond to
      persistent or formerly designated prolonged auras. Nine cases fulfilled ICHD-III
      beta status criteria. In our series, either 1.7% or 4.2% cases fulfilled ICDH-III
      beta or our definition, respectively. Regardless of the criteria, aura status
      patients were older at onset of status than those with typical aura, had a
      predominance of visual symptoms, normal neuroimaging and no sequelae. Status
      recurred in a few. CONCLUSION: Both criteria identify a similar population in
      terms of age, gender, main symptoms, imaging and outcome. Since patients with
      closely recurring auras might raise the same approach independently of the
      criteria, the use of more liberal criteria will allow more cases for detailed
      diagnosis and therapeutic analysis, eventually leading to the identification of
      subtypes.

PMID- 24740512
TI  - Molecules involved in the crosstalk between immune- and peripheral nerve Schwann
      cells.
AB  - Schwann cells are the myelinating glial cells of the peripheral nervous system
      and establish myelin sheaths on large caliber axons in order to accelerate their
      electrical signal propagation. Apart from this well described function, these
      cells revealed to exhibit a high degree of differentiation plasticity as they
      were shown to re- and dedifferentiate upon injury and disease as well as to
      actively participate in regenerative- and inflammatory processes. This review
      focuses on the crosstalk between glial- and immune cells observed in many
      peripheral nerve pathologies and summarizes functional evidences of molecules,
      regulators and factors involved in this process. We summarize data on Schwann
      cell's role presenting antigens, on interactions with the complement system, on
      Schwann cell surface molecules/receptors and on secreted factors involved in
      immune cell interactions or para-/autocrine signaling events, thus strengthening
      the view for a broader (patho) physiological role of this cell lineage. 

PMID- 24740516
TI  - Higher practice intensity is associated with higher quality of care but more
      avoidable admissions for medicare beneficiaries.
AB  - BACKGROUND: The relationship between practice intensity and the quality and
      outcomes of care has not been studied. OBJECTIVE: To examine the relationship
      between primary care physicians' costliness both for defined episodes of care and
      for defined patients and the quality and outcomes of care delivered to Medicare
      beneficiaries. STUDY DESIGN: Cross sectional analysis of physician survey data
      linked to Medicare claims. Physician costliness measures were calculated by
      comparing the episode specific and overall costs of care for their patients with
      the care delivered by other physicians. PARTICIPANTS: We studied physicians
      participating in the 2004-2005 Community Tracking Study Physician Survey linked
      with administrative claims from the Medicare program for the years 2004-2006.
      MAIN MEASURES: Proportion of eligible beneficiaries receiving each of seven
      preventive services and rates of preventable admissions for acute and chronic
      conditions. KEY RESULTS: The 2,211 primary care physician respondents included
      937 internists and 1,274 family or general physicians who were linked to more
      than 250,000 Medicare enrollees. Patients treated by more costly physicians
      (whether measured by the overall costliness index or the episode-level index)
      were more likely to receive recommended preventive services, but were also more
      likely to experience preventable admissions. For instance, physicians in the
      lowest quartile of costliness performed appropriate monitoring for hemoglobin A1C
      for diabetics 72.8% of the time, as compared with 81.9% for physicians in the
      highest quartile of costliness (p < 0.01). In contrast, patients treated by the
      physicians in the lowest quartile of episode costliness were admitted at a rate
      of 1.8/100 for both acute and chronic Prevention Quality Indicators (PQIs), as
      compared with 2.9/100 for both acute and chronic PQIs for those treated by
      physicians in the highest quartile of costliness (p < 0.001). CONCLUSIONS:
      Physician practice patterns are associated with the quality of preventive
      services delivered to Medicare patients. Ongoing efforts to influence physician
      practice patterns may have differential effects on different aspects of quality.

PMID- 24740517
TI  - Rational design, synthesis, and evaluation of tetrahydroxamic acid chelators for
      stable complexation of zirconium(IV).
AB  - Metals of interest for biomedical applications often need to be complexed and
      associated in a stable manner with a targeting agent before use. Whereas the
      fundamentals of most transition-metal complexation processes have been thoroughly
      studied, the complexation of Zr(IV) has been somewhat neglected. This metal has
      received growing attention in recent years, especially in nuclear medicine, with
      the use of (89) Zr, which a beta(+) -emitter with near ideal characteristics for
      cancer imaging. However, the best chelating agent known for this radionuclide is
      the trishydroxamate desferrioxamine B (DFB), the Zr(IV) complex of which exhibits
      suboptimal stability, resulting in the progressive release of (89) Zr in vivo.
      Based on a recent report demonstrating the higher thermodynamic stability of the
      tetrahydroxamate complexes of Zr(IV) compared with the trishydroxamate complexes
      analogues to DFB, we designed a series of tetrahydroxamic acids of varying
      geometries for improved complexation of this metal. Three macrocycles differing
      in their cavity size (28 to 36-membered rings) were synthesized by using a ring
      closing metathesis strategy, as well as their acyclic analogues. A solution study
      with (89) Zr showed the complexation to be more effective with increasing cavity
      size. Evaluation of the kinetic inertness of these new complexes in
      ethylenediaminetetraacetic acid (EDTA) solution showed significantly improved
      stabilities of the larger chelates compared with (89) Zr-DFB, whereas the smaller
      complexes suffered from insufficient stabilities. These results were rationalized
      by a quantum chemical study. The lower stability of the smaller chelates was
      attributed to ring strain, whereas the better stability of the larger cyclic
      complexes was explained by the macrocyclic effect and by the structural rigidity.
      Overall, these new chelating agents open new perspectives for the safe and
      efficient use of (89) Zr in nuclear imaging, with the best chelators providing
      dramatically improved stabilities compared with the reference DFB. 

PMID- 24740518
TI  - Altered cerebrospinal fluid levels of amyloid beta and amyloid precursor-like
      protein 1 peptides in Down's syndrome.
AB  - Down's syndrome (DS) patients develop early Alzheimer's disease pathology with
      abundant cortical amyloid plaques, likely due to overproduction of the amyloid
      precursor protein (APP), which subsequently leads to amyloid beta (Abeta)
      aggregation. This is reflected in cerebrospinal fluid (CSF) levels of the 42
      amino acid long Abeta peptide (Abeta1-42), which are increased in young DS
      patients and decreases with age. However, it is unclear whether DS also affects
      other aspects of Abeta metabolism, including production of shorter C- and N
      terminal truncated Abeta peptides, and production of peptides from the amyloid
      precursor-like protein 1 (APLP1), which is related to APP, and cleaved by the
      same enzymatic processing machinery. APLP1-derived peptides may be surrogate
      markers for Abeta1-42 production in the brain. Here, we used hybrid
      immunoaffinity-mass spectrometry and enzyme-linked immunosorbent assays to
      monitor several Abeta and APLP1 peptides in CSF from DS patients (n = 12) and
      healthy controls (n = 20). CSF levels of Abeta1-42 and three endogenous peptides
      derived from APLP1 (APL1beta25, APL1beta27 and APL1beta28) were decreased in DS
      compared with controls, while a specific Abeta peptide, Abeta1-28, was increased
      in a majority of the DS individuals. This study indicates that DS causes
      previously unknown specific alterations of APP and APLP1 metabolism.

PMID- 24740519
TI  - The slugs of Britain and Ireland: undetected and undescribed species increase a
      well-studied, economically important fauna by more than 20%.
AB  - The slugs of Britain and Ireland form a well-studied fauna of economic
      importance. They include many widespread European species that are introduced
      elsewhere (at least half of the 36 currently recorded British species are
      established in North America, for example). To test the contention that the
      British and Irish fauna consists of 36 species, and to verify the identity of
      each, a species delimitation study was conducted based on a geographically wide
      survey. Comparisons between mitochondrial DNA (COI, 16S), nuclear DNA (ITS-1) and
      morphology were investigated with reference to interspecific hybridisation.
      Species delimitation of the fauna produced a primary species hypothesis of 47
      putative species. This was refined to a secondary species hypothesis of 44
      species by integration with morphological and other data. Thirty six of these
      correspond to the known fauna (two species in Arion subgenus Carinarion were
      scarcely distinct and Arion (Mesarion) subfuscus consisted of two near-cryptic
      species). However, by the same criteria a further eight previously undetected
      species (22% of the fauna) are established in Britain and/or Ireland. Although
      overlooked, none are strictly morphologically cryptic, and some appear previously
      undescribed. Most of the additional species are probably accidentally introduced,
      and several are already widespread in Britain and Ireland (and thus perhaps
      elsewhere). At least three may be plant pests. Some evidence was found for
      interspecific hybridisation among the large Arion species (although not involving
      A. flagellus) and more unexpectedly in species pairs in Deroceras
      (Agriolimacidae) and Limacus (Limacidae). In the latter groups, introgression
      appears to have occurred in one direction only, with recently-invading lineages
      becoming common at the expense of long-established or native ones. The results
      show how even a well-studied, macroscopic fauna can be vulnerable to cryptic and
      undetected invasions and changes. 

PMID- 24740520
TI  - Influence of light-activation protocol on methacrylate resin-composite evaluated
      by dynamic mechanical analysis and degree of conversion.
AB  - The aim of this study was to evaluate the degree of conversion (DC) and to
      identify the viscoelastic properties: storage modulus (E'), loss modulus (E"),
      tangent delta (tan delta), and glass transition temperature (T g ) of a
      microhybrid resin-composite light-activated by three different protocols. A
      Filtek Z250 (3 M ESPE) shade A3 was inserted in a Teflon mold (21 mm * 5 mm * 1
      mm for viscoelastic properties; and 5 mm * 1 mm for DC) and light-activated
      according to the following light-activation protocols: (S) 1,000 mW/cm(2) * 19 s,
      (HP) 1,400 mW/cm(2) * 14 s, and (PE) 3,200 mW/cm(2) * 6 s, all set up to deliver
      19 J/cm(2). Viscoelastic properties was assessed by dynamic mechanical analysis
      (DMA) (n = 3), performed in single cantilever clamped mode. DC (n = 5) was
      measured by FTIR on top (T) and bottom (B) surfaces, and the data was submitted
      to a split-plot one-way ANOVA. For DC, there was a significant effect for surface
      factor and light-activation protocols factor. Top surface showed higher DC than B
      in all experimental conditions. Light-activation protocols S and HP resulted in
      higher DC than PE and were similar between them. Viscoelastic properties (E', E",
      tan delta, T g ) were not affected by light-activation protocols. It could be
      concluded that light-activation protocols influenced DC but not influenced the
      viscoelastic properties.

PMID- 24740521
TI  - Lack of antifungal effect of 1,064-nm long pulse Nd:YAG laser on the growth of
      Trichophyton rubrum.

PMID- 24740522
TI  - Impact of relative head sensitivity differences in multi-head gamma cameras.
AB  - Cerebral perfusion single photon emission computer tomography (SPECT) can be used
      to identify epileptogenic foci. A (99m)Tc ethyl cysteinate dimer SPECT of the
      brain showed clinically evident differences in uptake between the CT attenuation
      corrected image and the Chang attenuation corrected image. The upper right
      hemisphere of the brain showed apparent diffuse hyperperfusion in the CT
      attenuation corrected image while the Chang attenuation corrected image, after
      reconstruction that appears to average projections, showed symmetrical cerebral
      perfusion. On review of archived patient data, this artefact was also observed in
      multiple previous cerebral SPECT studies undertaken on the same camera. Phantom
      investigation was used to identify the cause of the artefact as a difference in
      relative head sensitivity. The investigation also characterised the extent and
      nature of this artefact for CT attenuation corrected images, Chang attenuation
      corrected images and non-attenuation corrected images.

PMID- 24740523
TI  - SCAI expert consensus statement for aorto-iliac arterial intervention appropriate
      use.
AB  - Aorto-iliac arterial occlusive disease is common and may cause a spectrum of
      chronic symptoms from intermittent claudication to critical limb ischemia.
      Treatment is indicated for symptoms that have failed lifestyle and medical
      therapies or occasionally to facilitate other interventional procedures such as
      TAVR and/or placement of hemodynamic assist devices. It is widely accepted that
      TASC A, B, and C lesions are best managed with endovascular intervention. In
      experienced hands, most TASC D lesions may be treated by endovascular methods,
      and with the development of chronic total occlusion devices, many aorto-iliac
      occlusions may be recanalized safely by endovascular means. Interventional
      cardiologists should be well versed in the anatomy, as well as the treatment of
      aorto-iliac disease, given their need to traverse these vessels during
      transfemoral procedures. Overall, aorto-iliac occlusive disease is more commonly
      being treated with an endovascular-first approach, using open surgery as a
      secondary option. This document was developed to guide physicians in the clinical
      decision-making related to the contemporary application of endovascular
      intervention among patients with aorto-iliac arterial disease.

PMID- 24740526
TI  - How microstructures affect air film dynamics prior to drop impact.
AB  - When a drop impacts a surface, a dimple can be formed due to the increased air
      pressure beneath the drop before it wets the surface. We employ a high-speed
      color interferometry technique to measure the evolution of the air layer profiles
      under millimeter-sized drops impacting hydrophobic micropatterned surfaces for
      impact velocities of typically 0.4 m s(-1). We account for the impact phenomena
      and show the influence of the micropillar spacing and height on the air layer
      profiles. A decrease in pillar spacing increases the height of the air dimple
      below the impacting drop. Before complete wetting, when the impacting drop only
      wets the top of the pillars, the air-droplet interface deforms in between the
      pillars. For large pillar heights the deformation is larger, but the dimple
      height is hardly influenced. 

PMID- 24740524
TI  - Extra virgin olive oil polyphenolic extracts downregulate inflammatory responses
      in LPS-activated murine peritoneal macrophages suppressing NFkappaB and MAPK
      signalling pathways.
AB  - Extra virgin olive oil (EVOO) is obtained from the fruit of the olive tree Olea
      europaea L. Phenolic compounds present in EVOO have recognized anti-oxidant and
      anti-inflammatory properties. However, the activity of the total phenolic
      fraction extracted from EVOO and the action mechanisms involved are not well
      defined. The present study was designed to evaluate the potential anti
      inflammatory mechanisms of the polyphenolic extract (PE) from EVOO on LPS
      stimulated peritoneal murine macrophages. Nitric oxide (NO) production was
      analyzed by the Griess method and intracellular reactive oxygen species (ROS) by
      fluorescence analysis. Moreover, changes in the protein expression of the pro
      inflammatory enzymes, inducible nitric oxide synthase (iNOS), cyclooxygenase
      (COX)-2 and microsomal prostaglandin E synthase-1 (mPGES-1), as well as the role
      of nuclear transcription factor kappa B (NFkappaB) and mitogen-activated protein
      kinase (MAPK) signalling pathways, were analyzed by Western blot. PE from EVOO
      reduced LPS-induced oxidative stress and inflammatory responses through
      decreasing NO and ROS generation. In addition, PE induced a significant down
      regulation of iNOS, COX-2 and mPGES-1 protein expressions, reduced MAPK
      phosphorylation and prevented the nuclear NFkappaB translocation. This study
      establishes that PE from EVOO possesses anti-inflammatory activities on LPS
      stimulated murine macrophages. 

PMID- 24740527
TI  - Dynamic kinetic resolution of dehydrocoronamic acid.
AB  - Dehydrocoronamic acid can be racemised by dehydration of an N-acyl derivative to
      an azlactone, which undergoes facile racemisation. For the N-trifluoroacetyl
      derivative, the racemisation process was combined with an enzymatic resolution,
      to achieve a dynamic kinetic resolution process by which the racemate can be
      converted to either enantiomer. 

PMID- 24740528
TI  - Efficacy of intravenous ketamine for treatment of chronic posttraumatic stress
      disorder: a randomized clinical trial.
AB  - IMPORTANCE: Few pharmacotherapies have demonstrated sufficient efficacy in the
      treatment of posttraumatic stress disorder (PTSD), a chronic and disabling
      condition. OBJECTIVE: To test the efficacy and safety of a single intravenous
      subanesthetic dose of ketamine for the treatment of PTSD and associated
      depressive symptoms in patients with chronic PTSD. DESIGN, SETTING, AND
      PARTICIPANTS: Proof-of-concept, randomized, double-blind, crossover trial
      comparing ketamine with an active placebo control, midazolam, conducted at a
      single site (Icahn School of Medicine at Mount Sinai, New York, New York). Forty
      one patients with chronic PTSD related to a range of trauma exposures were
      recruited via advertisements. INTERVENTIONS: Intravenous infusion of ketamine
      hydrochloride (0.5 mg/kg) and midazolam (0.045 mg/kg). MAIN OUTCOMES AND
      MEASURES: The primary outcome measure was change in PTSD symptom severity,
      measured using the Impact of Event Scale-Revised. Secondary outcome measures
      included the Montgomery-Asberg Depression Rating Scale, the Clinical Global
      Impression-Severity and -Improvement scales, and adverse effect measures,
      including the Clinician-Administered Dissociative States Scale, the Brief
      Psychiatric Rating Scale, and the Young Mania Rating Scale. RESULTS: Ketamine
      infusion was associated with significant and rapid reduction in PTSD symptom
      severity, compared with midazolam, when assessed 24 hours after infusion (mean
      difference in Impact of Event Scale-Revised score, 12.7 [95% CI, 2.5-22.8]; P =
      .02). Greater reduction of PTSD symptoms following treatment with ketamine was
      evident in both crossover and first-period analyses, and remained significant
      after adjusting for baseline and 24-hour depressive symptom severity. Ketamine
      was also associated with reduction in comorbid depressive symptoms and with
      improvement in overall clinical presentation. Ketamine was generally well
      tolerated without clinically significant persistent dissociative symptoms.
      CONCLUSIONS AND RELEVANCE: This study provides the first evidence for rapid
      reduction in symptom severity following ketamine infusion in patients with
      chronic PTSD. If replicated, these findings may lead to novel approaches to the
      pharmacologic treatment of patients with this disabling condition. TRIAL
      REGISTRATION: clinicaltrials.gov Identifier: NCT00749203.

PMID- 24740529
TI  - Graphene-based sensors for detection of heavy metals in water: a review.
AB  - Graphene (G) is attracting significant attention because of its unique physical
      and electronic properties. The production of graphene through the reduction of
      graphene oxide (GO) is a low-cost method. The reduction of GO can further lead to
      electrically conductive reduced GO. These graphene-based nanomaterials are
      attractive for high-performance water sensors due to their unique properties,
      such as high specific surface areas, high electron mobilities, and exceptionally
      low electronic noise. Because of potential risks to the environment and human
      health arising from heavy-metal pollution in water, G-/GO-based water sensors are
      being developed for rapid and sensitive detection of heavy-metal ions. In this
      review, a general introduction to graphene and GO properties, as well as their
      syntheses, is provided. Recent advances in optical, electrochemical, and
      electrical detection of heavy-metal ions using graphene or GO are then
      highlighted. Finally, challenges facing G/GO-based water sensor development and
      outlook for future research are discussed. 

PMID- 24740530
TI  - [Diabetes care and incidence of severe hypoglycemia in nursing home facilities
      and nursing services: The Heidelberg Diabetes Study].
AB  - AIM: The goal of this study was to perform a structured analysis of the treatment
      quality and acute complications of geriatric patients with diabetes mellitus (DM)
      cared for by nursing services and nursing home facilities. Secondly, structural
      problems and potentials for improvement in the care of multimorbid older people
      with DM treated by nursing homes and nursing services were analysed from the
      viewpoint of geriatric nurses, managers of nursing homes and general
      practitioners. METHODS: In all, 77 older persons with DM from 13 nursing homes
      and 3 nursing services were included in the analysis (76.6% female, HbA1c 6.9 +/-
      1.4%, age 81.6 +/- 9.9 years). Structural problems and potentials for improvement
      were collected from 95 geriatric nurses, 9 managers of nursing homes and 6
      general practitioners using semistandardized questionnaires. RESULTS: Metabolic
      control was too strict in care-dependent older people with DM (mean HbA1c value:
      6.9 +/- 1.4 %; recommended by guidelines: 7-8%). The measurement of HbA1c was
      performed in 16 of 77 people (20.8%) within the last year despite a high
      visitation frequency of the general practitioners (12.7 +/- 7.7 within the last 6
      months). The incidence of severe hypoglycemia was 7.8%/patient/year. Regarding
      the management in case of diabetes-related acute complications 33 geriatric
      nurses (34.7%) stated not having any written standard (nursing home 39%,
      geriatric services 16.7%). CONCLUSION: Complex insulin therapies are still used
      in older people with DM with the consequence of a high incidence of severe
      hypoglycemia. Concrete management standards in the case of diabetes-related acute
      complications for geriatric nurses are lacking for more than one third of the
      nursing services.

PMID- 24740531
TI  - Design of pharmaceutical products to meet future patient needs requires
      modification of current development paradigms and business models.
AB  - Drugs represent the most common intervention strategy for managing acute and
      chronic medical conditions. In light of demographic change and the increasing age
      of patients, the classic model of drug research and development by the
      pharmaceutical industry and drug prescription by physicians is reaching its
      limits. Different stakeholders, e.g. industry, regulatory authorities, health
      insurance systems, physicians etc., have at least partially differing interests
      regarding the process of healthcare provision. The primary responsibility for the
      correct handling of medication and adherence to treatment schedules lies with the
      recipient of a drug-based therapy, i.e. the patient. It is thus necessary to
      interactively involve elderly patients, as well as the other stakeholders, in the
      development of medication and medication application devices, and in clinical
      trials. This approach will provide the basis for developing a strategy that
      better meets patients' needs, thus resulting in improved adherence to treatment
      schedules and better therapeutic outcomes. 

PMID- 24740532
TI  - Sequential intra-intercellular nanoparticle delivery system for deep tumor
      penetration.
AB  - To achieve deep tumor penetration of large-sized nanoparticles (NPs), we have
      developed a reversible swelling-shrinking nanogel in response to pH variation for
      a sequential intra-intercellular NP delivery. The nanogel had a crosslinked
      polyelectrolyte core, consisting of N-lysinal-N'-succinyl chitosan and poly(N
      isopropylacrylamide), and a crosslinked bovine serum albumin shell, which was
      able to swell in an acidic environment and shrink back under neutral conditions.
      The swelling resulted in a rapid release of the encapsulated chemotherapeutics in
      the cancer cells for efficient cytotoxicity. After being liberated from the dead
      cells, the contractive nanogel could infect neighboring cancer cells closer to
      the center of the tumor tissue. 

PMID- 24740533
TI  - False positivity of ETV6/RUNX1 detected by FISH in healthy newborns and adults.
AB  - The leukemia-associated ETV6-RUNX1-translocation frequently emerges prenatally.
      Reverse-transcriptase PCR screening may indicate presence of ETV6-RUNX1
      transcripts in random cord blood samples. Subsequent cell enrichment validation
      finds significantly lower levels than validation applying fluorescence in situ
      hybridization (FISH) (<10(-5) vs. 10(-3) to 10(-4)). Using three FISH probe sets,
      we screened 179,000 cells from ETV6-RUNX1-positive dilution series, healthy
      adults and random cord blood samples. The t(12;21) single fusion extra signal
      translocation probe and the ETV6 break apart probe gave false positive results
      mimicking ETV6-RUNX1-positive cell levels of 10(-3). This questions the paradigm
      that 1% of newborns have ETV6-RUNX1-positive cells at levels of 10(-3) to 10(-4).

PMID- 24740534
TI  - Interventions for iatrogenic inferior alveolar and lingual nerve injury.
AB  - BACKGROUND: Iatrogenic injury of the inferior alveolar or lingual nerve or both
      is a known complication of oral and maxillofacial surgery procedures. Injury to
      these two branches of the mandibular division of the trigeminal nerve may result
      in altered sensation associated with the ipsilateral lower lip or tongue or both
      and may include anaesthesia, paraesthesia, dysaesthesia, hyperalgesia, allodynia,
      hypoaesthesia and hyperaesthesia. Injury to the lingual nerve may also affect
      taste perception on the affected side of the tongue. The vast majority
      (approximately 90%) of these injuries are temporary in nature and resolve within
      eight weeks. However, if the injury persists beyond six months it is deemed to be
      permanent. Surgical, medical and psychological techniques have been used as a
      treatment for such injuries, though at present there is no consensus on the
      preferred intervention, or the timing of the intervention. OBJECTIVES: To
      evaluate the effects of different interventions and timings of interventions to
      treat iatrogenic injury of the inferior alveolar or lingual nerves. SEARCH
      METHODS: We searched the following electronic databases: the Cochrane Oral Health
      Group's Trial Register (to 9 October 2013), the Cochrane Central Register of
      Controlled Trials (CENTRAL) (The Cochrane Library 2013, Issue 9), MEDLINE via
      OVID (1946 to 9 October 2013) and EMBASE via OVID (1980 to 9 October 2013). No
      language restrictions were placed on the language or date of publication when
      searching the electronic databases. SELECTION CRITERIA: Randomised controlled
      trials (RCTs) involving interventions to treat patients with neurosensory defect
      of the inferior alveolar or lingual nerve or both as a sequela of iatrogenic
      injury. DATA COLLECTION AND ANALYSIS: We used the standard methodological
      procedures expected by The Cochrane Collaboration. We performed data extraction
      and assessment of the risk of bias independently and in duplicate. We contacted
      authors to clarify the inclusion criteria of the studies. MAIN RESULTS: Two
      studies assessed as at high risk of bias, reporting data from 26 analysed
      participants were included in this review. The age range of participants was from
      17 to 55 years. Both trials investigated the effectiveness of low-level laser
      treatment compared to placebo laser therapy on inferior alveolar sensory deficit
      as a result of iatrogenic injury.Patient-reported altered sensation was partially
      reported in one study and fully reported in another. Following treatment with
      laser therapy, there was some evidence of an improvement in the subjective
      assessment of neurosensory deficit in the lip and chin areas compared to placebo,
      though the estimates were imprecise: a difference in mean change in neurosensory
      deficit of the chin of 8.40 cm (95% confidence interval (CI) 3.67 to 13.13) and a
      difference in mean change in neurosensory deficit of the lip of 21.79 cm (95% CI
      5.29 to 38.29). The overall quality of the evidence for this outcome was very
      low; the outcome data were fully reported in one small study of 13 patients, with
      differential drop-out in the control group, and patients suffered only partial
      loss of sensation. No studies reported on the effects of the intervention on the
      remaining primary outcomes of pain, difficulty eating or speaking or taste. No
      studies reported on quality of life or adverse events.The overall quality of the
      evidence was very low as a result of limitations in the conduct and reporting of
      the studies, indirectness of the evidence and the imprecision of the results.
      AUTHORS' CONCLUSIONS: There is clearly a need for randomised controlled clinical
      trials to investigate the effectiveness of surgical, medical and psychological
      interventions for iatrogenic inferior alveolar and lingual nerve injuries.
      Primary outcomes of this research should include: patient-focused morbidity
      measures including altered sensation and pain, pain, quantitative sensory testing
      and the effects of delayed treatment.

PMID- 24740536
TI  - A recipe for pluripotency: the correct sp(l)ices make all the difference. Focus
      on "Induced overexpression of OCT4A in human embryonic stem cells increases
      cloning efficiency".

PMID- 24740535
TI  - Cellular mechanisms of tissue fibrosis. 7. New insights into the cellular
      mechanisms of pulmonary fibrosis.
AB  - Idiopathic pulmonary fibrosis (IPF) is a devastating disease characterized by
      severe and progressive scar formation in the gas-exchange regions of the lung.
      Despite years of research, therapeutic treatments remain elusive and there is a
      pressing need for deeper mechanistic insights into the pathogenesis of the
      disease. In this article, we review our current knowledge of the triggers and/or
      perpetuators of pulmonary fibrosis with special emphasis on the alveolar
      epithelium and the underlying mesenchyme. In doing so, we raise a number of
      questions highlighting critical voids and limitations in our current
      understanding and study of this disease. 

PMID- 24740537
TI  - A positive feedback loop involving Erk5 and Akt turns on mesangial cell
      proliferation in response to PDGF.
AB  - Platelet-derived growth factor BB and its receptor (PDGFRbeta) play a pivotal
      role in the development of renal glomerular mesangial cells. Their roles in
      increased mesangial cell proliferation during mesangioproliferative
      glomerulonephritis have long been noted, but the operating logic of signaling
      mechanisms regulating these changes remains poorly understood. We examined the
      role of a recently identified MAPK, Erk5, in this process. PDGF increased the
      activating phosphorylation of Erk5 and tyrosine phosphorylation of proteins in a
      time-dependent manner. A pharmacologic inhibitor of Erk5, XMD8-92, abrogated PDGF
      induced DNA synthesis and mesangial cell proliferation. Similarly, expression of
      dominant negative Erk5 or siRNAs against Erk5 blocked PDGF-stimulated DNA
      synthesis and proliferation. Inhibition of Erk5 attenuated expression of cyclin
      D1 mRNA and protein, resulting in suppression of CDK4-mediated phosphorylation of
      the tumor suppressor protein pRb. Expression of cyclin D1 or CDK4 prevented the
      dominant negative Erk5- or siErk5-mediated inhibition of DNA synthesis and
      mesangial cell proliferation induced by PDGF. We have previously shown that
      phosphatidylinositol 3-kinase (PI3-kinase) contributes to PDGF-induced
      proliferation of mesangial cells. Inhibition of PI3-kinase blocked PDGF-induced
      phosphorylation of Erk5. Since PI3-kinase acts through Akt, we determined the
      role of Erk5 on Akt phosphorylation. XMD8-92, dominant negative Erk5, and siErk5
      inhibited phosphorylation of Akt by PDGF. Interestingly, we found inhibition of
      PDGF-induced Erk5 phosphorylation by a pharmacological inhibitor of Akt kinase
      and kinase dead Akt in mesangial cells. Thus our data unfold the presence of a
      positive feedback microcircuit between Erk5 and Akt downstream of PI3-kinase
      nodal point for PDGF-induced mesangial cell proliferation. 

PMID- 24740538
TI  - Jun kinase-induced overexpression of leukemia-associated Rho GEF (LARG) mediates
      sustained hypercontraction of longitudinal smooth muscle in inflammation.
AB  - The signaling pathways mediating sustained contraction of mouse colonic
      longitudinal smooth muscle and the mechanisms involved in hypercontractility of
      this muscle layer in response to cytokines and TNBS-induced colitis have not been
      fully explored. In control longitudinal smooth muscle cells, ACh acting via m3
      receptors activated sequentially Galpha12, RhoGEF (LARG), and the RhoA/Rho kinase
      pathway. There was abundant expression of MYPT1, minimal expression of CPI-17,
      and a notable absence of a PKC/CPI-17 pathway. LARG expression was increased in
      longitudinal muscle cells isolated from muscle strips cultured for 24 h with IL
      1beta or TNF-alpha or obtained from the colon of TNBS-treated mice. The increase
      in LARG expression was accompanied by a significant increase in ACh-stimulated
      Rho kinase and ZIP kinase activities, and sustained muscle contraction. The
      increase in LARG expression, Rho kinase and ZIP kinase activities, and sustained
      muscle contraction was abolished in cells pretreated with the Jun kinase
      inhibitor, SP600125. Expression of the MLCP activator, telokin, and MLCP activity
      were also decreased in longitudinal muscle cells from TNBS-treated mice or from
      strips treated with IL-1beta or TNF-alpha. In contrast, previous studies had
      shown that sustained contraction in circular smooth muscle is mediated by
      sequential activation of Galpha13, p115RhoGEF, and dual RhoA-dependent pathways
      involving phosphorylation of MYPT1 and CPI-17. In colonic circular smooth muscle
      cells isolated from TNBS-treated mice or from strips treated with IL-1beta or TNF
      alpha, CPI-17 expression and sustained muscle contraction were decreased. The
      disparate changes in the two muscle layers contribute to intestinal dysmotility
      during inflammation.

PMID- 24740539
TI  - Jnk2 deletion disrupts intestinal mucosal homeostasis and maturation by
      differentially modulating RNA-binding proteins HuR and CUGBP1.
AB  - Homeostasis and maturation of the mammalian intestinal epithelium are preserved
      through strict regulation of cell proliferation, apoptosis, and differentiation,
      but the exact mechanism underlying this process remains largely unknown. c-Jun
      NH2-terminal kinase 2 (JNK2) is highly expressed in the intestinal mucosa, and
      its activation plays an important role in proliferation and also mediates
      apoptosis in cultured intestinal epithelial cells (IECs). Here, we investigated
      the in vivo function of JNK2 in the regulation of intestinal epithelial
      homeostasis and maturation by using a targeted gene deletion approach. Targeted
      deletion of the jnk2 gene increased cell proliferation within the crypts in the
      small intestine and disrupted mucosal maturation as indicated by decreases in the
      height of villi and the villus-to-crypt ratio. JNK2 deletion also decreased
      susceptibility of the intestinal epithelium to apoptosis. JNK2-deficient
      intestinal epithelium was associated with an increase in the level of the RNA
      binding protein HuR and with a decrease in the abundance of CUG-binding protein 1
      (CUGBP1). In studies in vitro, JNK2 silencing protected intestinal epithelial
      cell-6 (IEC-6) cells against apoptosis and this protection was prevented by
      inhibiting HuR. Ectopic overexpression of CUGBP1 repressed IEC-6 cell
      proliferation, whereas CUGBP1 silencing enhanced cell growth. These results
      indicate that JNK2 is essential for maintenance of normal intestinal epithelial
      homeostasis and maturation under biological conditions by differentially
      modulating HuR and CUGBP1.

PMID- 24740540
TI  - Oxidative stress-induced mitochondrial fragmentation and movement in skeletal
      muscle myoblasts.
AB  - Mitochondria are dynamic organelles, capable of altering their morphology and
      function. However, the mechanisms governing these changes have not been fully
      elucidated, particularly in muscle cells. We demonstrated that oxidative stress
      with H2O2 resulted in a 41% increase in fragmentation of the mitochondrial
      reticulum in myoblasts within 3 h of exposure, an effect that was preceded by a
      reduction in membrane potential. Using live cell imaging, we monitored
      mitochondrial motility and found that oxidative stress resulted in a 30%
      reduction in the average velocity of mitochondria. This was accompanied by
      parallel reductions in both organelle fission and fusion. The attenuation in
      mitochondrial movement was abolished by the addition of N-acetylcysteine. To
      investigate whether H2O2-induced fragmentation was mediated by dynamin-related
      protein 1, we incubated cells with mDivi1, an inhibitor of dynamin-related
      protein 1 translocation to mitochondria. mDivi1 attenuated oxidative stress
      induced mitochondrial fragmentation by 27%. Moreover, we demonstrated that
      exposure to H2O2 upregulated endoplasmic reticulum-unfolded protein response
      markers before the initiation of mitophagy signaling and the mitochondrial
      unfolded protein response. These findings indicate that oxidative stress is a
      vital signaling mechanism in the regulation of mitochondrial morphology and
      motility.

PMID- 24740543
TI  - Heparanase induces inflammatory cell recruitment in vivo by promoting adhesion to
      vascular endothelium.
AB  - Heparanase (HPSE1) is known to be involved in mechanisms of metastatic tumor cell
      migration. This enzyme selectively cleaves heparan sulfate proteoglycans (HSPG),
      which are ubiquitously expressed in mammals and are known to be involved in
      regulating the activity of an array of inflammatory mediators. In the present
      study, we have investigated the effects of human recombinant heparanase, the
      inactive precursor of this enzyme (proheparanase) and enzymatically inactivated
      heparanase, on inflammatory cell recruitment in the rat and on human leukocyte
      endothelial adhesion in vitro. Intraperitoneal injection of heparanase (500 MUg)
      induced a significant inflammatory cell infiltrate in the rat, as assessed by
      peritoneal lavage 4 h later. Intravital microscopy of the mesenteric
      microcirculation of anesthetized rats showed an increase in rolling and adherent
      cells in postcapillary venules that was sensitive to heparin, a nonselective
      inhibitor of heparanase activity. In vitro, heparanase augmented the adhesion of
      human neutrophils and mononuclear cells to human umbilical vein endothelial cells
      in a concentration-dependent manner. Proheparanase had similar effects to the
      active enzyme both with respect to leukocyte accumulation in the peritoneal
      cavity and adhesion in vitro. However, heat-inactivated heparanase induced cell
      adhesion in vitro but was without effect in vivo. Together, these data indicate a
      role for heparanase in inflammatory cell trafficking in vivo that appears to
      require enzymatic activity.

PMID- 24740542
TI  - Host endothelial S1PR1 regulation of vascular permeability modulates tumor
      growth.
AB  - Understanding vascular growth and maturation in developing tumors has important
      implications for tumor progression, spread, and ultimately host survival.
      Modulating the signaling of endothelial G protein-coupled receptors (GPCRs) in
      blood and lymphatic vessels can enhance or limit tumor progression. Sphingosine 1
      phosphate receptor 1 (S1PR1) is a GPCR for circulating lysophospholipid S1P that
      is highly expressed in blood and lymphatic vessels. Using the S1PR1- enhanced
      green fluorescent protein (eGFP) mouse model in combination with intravital
      imaging and pharmacologic modulation of S1PR1 signaling, we show that boundary
      conditions of high and low S1PR1 signaling retard tumor progression by enhancing
      or destabilizing neovasculature integrity, respectively. In contrast, midrange
      S1PR1 signaling, achieved by receptor antagonist titration, promotes abundant
      growth of small, organized vessels and thereby enhances tumor progression.
      Furthermore, in vivo S1PR1 antagonism supports lung colonization by circulating
      tumor cells. Regulation of endothelial S1PR1 dynamically controls vascular
      integrity and maturation and thus modulates angiogenesis, tumor growth, and
      hematogenous metastasis.

PMID- 24740541
TI  - Cellular mechanisms of tissue fibrosis. 8. Current and future drug targets in
      fibrosis: focus on Rho GTPase-regulated gene transcription.
AB  - Tissue fibrosis occurs with excessive extracellular matrix deposition from
      myofibroblasts, resulting in tissue scarring and inflammation. It is driven by
      multiple mediators, such as the G protein-coupled receptor ligands
      lysophosphatidic acid and endothelin, as well as signaling by transforming growth
      factor-beta, connective tissue growth factor, and integrins. Fibrosis contributes
      to 45% of deaths in the developed world. As current therapeutic options for
      tissue fibrosis are limited and organ transplantation is the only effective
      treatment for end-stage disease, there is an imminent need for efficacious
      antifibrotic therapies. This review discusses the various molecular pathways
      involved in fibrosis. It highlights the Rho GTPase signaling pathway and its
      downstream gene transcription output through myocardin-related transcription
      factor and serum response factor as a convergence point for targeting this
      complex set of diseases.

PMID- 24740544
TI  - Using instructive feedback to teach category names to children with autism.
AB  - We evaluated the effects of instructive feedback (IF) on the emergence of spoken
      category names with 2 children who had been diagnosed with autism. IF stimuli
      were presented during listener discrimination training and consisted of
      presenting the category name associated with each target stimulus. Results
      suggest that participants acquired the speaker relations in the absence of
      prompting and reinforcement. Clinical implications and future research on the use
      of IF as a teaching procedure for children with autism are discussed. 

PMID- 24740545
TI  - Cushing's syndrome in type 2 diabetes patients with poor glycemic control.
AB  - Cushing's syndrome may be more frequent in some specific patient groups such as
      type 2 diabetes and obesity. The aim of this study was to investigate the
      prevalence of Cushing's syndrome in outpatients with type 2 diabetes with poor
      glycemic control despite at least 3-months insulin therapy. Outpatients with type
      2 diabetes whose glycemic control is poor (Hb Alc value >7 %) despite receiving
      at least 3-months long insulin treatment (insulin alone or insulin with oral
      antidiabetics) were included. Patients with classic features of Cushing's
      syndrome were excluded. Overnight 1 mg dexamethasone suppression test (DST) was
      performed as a screening test. A total of 277 patients with type 2 diabetes whose
      glycemic control is poor (Hb Alc value >7 %) despite insulin therapy were
      included. Two of the 277 patients with type 2 diabetes were diagnosed with
      Cushing's syndrome (0.72 %). Hypertension was statistically more frequent in the
      patients with cortisol levels >=1.8 MUg/dL than the patients with cortisol levels
      <1.8 MUg/dL after overnight 1 mg DST (p = 0.041). Statistically significant
      correlation was determined between cortisol levels after 1 mg DST and age, daily
      insulin dose (r = 0.266 and p < 0.001, r = 0.163 and p = 0.008, respectively).
      According to our findings, the prevalence of Cushing's syndrome among patients
      with type 2 diabetes with poor glycemic control despite insulin therapy is much
      higher than in the general population. The patients with type 2 diabetes with
      poor glycemic control despite at least three months of insulin therapy should be
      additionally tested for Cushing's syndrome if they have high dose insulin
      requirements.

PMID- 24740546
TI  - Perioperative androstenedione kinetics in women undergoing laparoscopic ovarian
      drilling: a prospective study.
AB  - We evaluated perioperative androstenedione levels in laparoscopic ovarian
      drilling (LOD) for polycystic ovary syndrome (PCOS) and whether an intraoperative
      androstenedione change was predictive for spontaneous ovulation. In a prospective
      study, 21 anovulatory women with clomiphene citrate-resistant PCOS who underwent
      LOD and eight female controls who underwent diagnostic laparoscopy for
      infertility were included. Perioperatively, blood was drawn one day before
      surgery, directly before skin incision, ten minutes after surgery, and after two
      days. Within three months, spontaneous ovulation occurred in 15 women (71.4 %).
      For both the PCOS and the control group, an androstenedione increase was found
      from one day before surgery to skin incision (p < 0.05). In PCOS women, there was
      an intraoperative androstenedione decrease (median 3.5, IQR 2.2-4.8 vs. median
      2.6, IQR 1.4-2.6 ng/ml, p = 0.002). In multivariate analysis, only higher
      preoperative androstenedione (odds ratio, OR 6.53) and luteinizing hormone levels
      (OR 7.31), as well as secondary infertility (OR 5.40), were associated with
      higher rates of postoperative spontaneous ovulation (p < 0.001). Androstendione
      declines significantly during LOD. However, intraoperative kinetics are not
      useful for the prediction of spontaneous ovulation after LOD, in contrast to
      preoperative androstenedione and LH levels, as well as a history of previous
      pregnancies.

PMID- 24740548
TI  - Reactivity index based on orbital energies.
AB  - This study shows that the chemical reactivities depend on the orbital energy gaps
      contributing to the reactions. In the process where a reaction only makes
      progress through charge transfer with the minimal structural transformation of
      the reactant, the orbital energy gap gradient (OEGG) between the electron
      donating and electron-accepting orbitals is proven to be very low. Using this
      relation, a normalized reaction diagram is constructed by plotting the normalized
      orbital energy gap with respect to the normalized intrinsic reaction coordinate.
      Application of this reaction diagram to 43 fundamental reactions showed that the
      majority of the forward reactions provide small OEGGs in the initial stages, and
      therefore, the initial processes of the forward reactions are supposed to proceed
      only through charge transfer. Conversely, more than 60% of the backward reactions
      are found to give large OEGGs implying very slow reactions associated with
      considerable structural transformations. Focusing on the anti-activation-energy
      reactions, in which the forward reactions have higher barriers than those of the
      backward ones, most of these reactions are shown to give large OEGGs for the
      backward reactions. It is also found that the reactions providing large OEGGs in
      the forward directions inconsistent with the reaction rate constants are
      classified into SN 2, symmetric, and methyl radical reactions. Interestingly,
      several large-OEGG reactions are experimentally established to get around the
      optimum pathways. This indicates that the reactions can take significantly
      different pathways from the optimum ones provided no charge transfer proceeds
      spontaneously without the structural transformations of the reactants.

PMID- 24740547
TI  - Baseline prevalence and type distribution of human papillomavirus in healthy
      Chinese women aged 18-25 years enrolled in a clinical trial.
AB  - Baseline human papillomavirus (HPV) prevalence and type distribution were
      evaluated in young Chinese women enrolled in a clinical trial of an HPV vaccine
      (ClinicalTrials.gov registration NCT00779766). Cervical specimens and blood
      samples were collected at baseline from women aged 18-25 years (n = 6,051) from
      four sites across Jiangsu province. Cervical specimens were tested for HPV DNA by
      SPF10 PCR-DEIA-LiPA25 version 1, and HPV-16/18 type-specific polymerase chain
      reaction. Anti-HPV-16 and anti-HPV-18 antibody titres were quantified by enzyme
      linked immunosorbent assay. At baseline, 15.3% of women were DNA positive for any
      of 14 HPV high-risk (hr) types (HPV-16/18/31/33/35/39/45/51/52/56/58/59/66/68).
      The most commonly detected hrHPV types in cervical specimens were HPV-52 (4.0%)
      and HPV-16 (3.7%). High-risk HPV DNA-positivity increased with severity of
      cytological abnormalities: 39.3% in atypical squamous cells of undetermined
      significance, 85.0% in low-grade squamous intraepithelial lesions and 97.8% in
      high-grade squamous intraepithelial lesions (HSIL). The hrHPV types most
      frequently detected in HSIL were HPV-16 (63.0%), HPV-18 (17.4%), HPV-52 (17.4%),
      HPV-58 (15.2%) and HPV-33 (15.2%). The hrHPV types most frequently detected in
      cervical intraepithelial neoplasia 2+ were HPV-16 (66.1%), HPV-33 (16.1%), HPV-52
      (16.1%), HPV-58 (14.5%) and HPV-51 (11.3%). Multiple hrHPV infections were
      reported for 24.4% of hrHPV DNA positive women. Regardless of baseline HPV DNA
      status, 30.5% and 16.0% of subjects were initially seropositive for anti-HPV-16
      and anti-HPV-18, respectively. In conclusion, the high baseline seropositivity
      rate and intermediate prevalence of cervical hrHPV types in Chinese women aged 18
      25 years underlines the importance of early HPV vaccination in this population.

PMID- 24740549
TI  - Analysis of cytosolic pH changes in thymocytes during early apoptosis with
      improved three-channel real-time fluorescence imaging.
AB  - Cytosolic pH changes in single thymocytes in the early stages of apoptosis were
      examined with spectral-crosstalk-improved three-channel real-time fluorescence
      imaging. Spectral crosstalk was greatly reduced by this improved image processing
      method. Compared with normal thymocytes, the improved image processing method
      showed that the cytosolic pH value of thymocytes undergoing apoptosis was lower.
      A slight diversity in the intracellular pH values of samples subjected to
      different drug treatments was also observed. This new image processing method is
      beneficial to the application of the three-channel real-time fluorescence imaging
      to biological processes. 

PMID- 24740550
TI  - Automated enumeration and viability measurement of canine stromal vascular
      fraction cells using fluorescence-based image cytometry method.
AB  - In recent years, the lipoaspirate collected from adipose tissue has been seen as
      a valuable source of adipose-derived mesenchymal stem cells for autologous
      cellular therapy. For multiple applications, adipose-derived mesenchymal stem
      cells are isolated from the stromal vascular fraction (SVF) of adipose tissue.
      Because the fresh stromal vascular fraction typically contains a heterogeneous
      mixture of cells, determining cell concentration and viability is a crucial step
      in preparing fraction samples for downstream processing. Due to a large amount of
      cellular debris contained in the SVF sample, as well as counting irregularities
      standard manual counting can lead to inconsistent results. Advancements in
      imaging and optics technologies have significantly improved the image-based
      cytometric analysis method. In this work, we validated the use of fluorescence
      based image cytometry for SVF concentration and viability measurement, by
      comparing to standard flow cytometry and manual hemocytometer. The concentration
      and viability of freshly collected canine SVF samples are analyzed, and the
      results highly correlated between all three methods, which validated the image
      cytometry method for canine SVF analysis, and potentially for SVF from other
      species.

PMID- 24740551
TI  - A sensitive Schiff-base fluorescent chemosensor for the selective detection of
      Zn2+.
AB  - A Schiff-base fluorescent probe - N, N(/)-bis(salicylidene) trans 1, 2 -
      diaminocyclohexane (H 2 L) was synthesized and evaluated as a chemoselective
      Zn(2+) sensor. Upon treatment with Zn(2+), the complexation of H 2 L with Zn(2+)
      resulted in a bathochromic shift with a pronounced enhancement in the
      fluorescence intensity in ethanol solution. Moreover, other common alkali,
      alkaline earth and transition metal ions failed to induce response or minimal
      spectral changes. Notably, this chemosensor could distinguish clearly Zn(2+) from
      Cd(2+). The stoichiometric ratio and association constant were evaluated using
      Benesi - Hildebrand relation giving 1:1 stoichiometry. This further corroborated
      1:1 complex formation based on Job's plot analyses.

PMID- 24740552
TI  - Modified Si-Miao-San () regulates adipokine expression and ameliorates insulin
      resistance by targeting IKKbeta/Insulin receptor substrate-1 in mice.
AB  - OBJECTIVE: To evaluate modified Si-Miao-San (mSMS, ) regulation of insulin
      sensitivity and explore the molecular mechanism by which mSMS inhibits
      inflammation and improves insulin action in mice. METHODS: Insulin resistant
      model in mice was prepared by stimulation with macrophage-derived condition
      medium (Mac-CM) and the effects of mSMS on oral glucose tolerance, insulin
      sensitivity and liver glycogen content in mice was observed. The mice adipose
      tissue was isolated and the regulation of inflammation-related adipokine
      expression and insulin phosphatidylinositol 3-kinase (PI3K) signaling
      transduction by mSMS was investigated. Effect of mSMS on insulin-mediated glucose
      uptake was also investigated in adipocytes. RESULTS: Oral administration of mSMS
      improved glucose tolerance in mice. Treatment of mice with Mac-CM resulted in
      glucose intolerance in mice and this change was effectively reversed by mSMS.
      Meanwhile, mSMS enhanced insulin sensitivity and increased glucose load
      stimulated liver glycogen when mice were exposed to Mac-CM. Mac-CM stimulation
      induced dysregulation of adipokine expression in adipose tissue of mice. mSMS
      downregulated tumor necrosis factor alpha and interleukin 6 (IL-6) overexpression
      and upregulated adiponectin and peroxisomal proliferator activated receptor gamma
      with inhibition of inhibitory kappa B kinase-beta (IKKbeta) and p65
      phophsphorylation. Meanwhile, mSMS inhibited IL-6 production and increased
      adiponectin secretion in adipocytes against Mac-CM insult. Mac-CM challenge
      impaired insulin phosphatidylinositol 3 kinase (PI3K) signaling in adipose
      tissue. Oral administration mSMS inhibited inflammation-induced serine
      phosphorylation of insulin receptor substrate-1 (IRS-1) and restored insulin
      mediated tyrosine phosphorylation, and thereby facilitated insulin PI3K signaling
      manifested by restoration of Akt phosphorylation. The resultant improvement of
      insulin sensitivity promoted insulin-stimulated glucose uptake when adipocytes
      were exposed to Mac-CM. CONCLUSIONS: mSMS improves glucose tolerance in mice by
      enhancing insulin sensitivity in mice. mSMS inhibits IKKbeta/NF kappa B (p65)
      dependent inflammatory response with beneficial regulation of adipokine
      expression in adipose tissue. mSMS inhibits inflammation and improves insulin
      sensitivity by blocking inflammatory interaction between IKKbeta/IRS-1.

PMID- 24740554
TI  - Evaluation of analgesic, sedative effects and antimigraine mechanism of Qilong
      Toutong Granule () in rodents.
AB  - OBJECTIVE: To evaluate the analgesic and sedative effects of Qilong Toutong
      Granule (, QTG) and explore its possible mechanisms. METHODS: Kunming mice were
      randomly divided into 6 groups: normal control group, Zhengtian Pill (, ZTP)
      group, Western medicine group, and high-dose (5.2 g/kg), medium-dose (2.6 g/kg)
      and low-dose (1.3 g/kg) of QTG groups. After completing the prophylactic
      treatment for 3 days, hot-plate test and acetic acid-induced writhing test were
      used to assess the analgesic effect, and spontaneous locomotor test and sodium
      pentobarbital-induced hypnosis activity were adopted to estimate the sedative
      effect. Sprague-Dawley rats were grouped into normal control group, model group,
      ZTP group, rizatriptan group, and high-dose (3.6 g/kg), medium-dose (1.8 g/kg),
      and low-dose (0.9 g/kg) of QTG groups. After gavage for continuous 7 days, rats
      were intraperitoneally injected nitroglycerin, and 4 h later, blood samples were
      collected from postcava for measuring the levels of plasma calcitonin gene
      related peptide (CGRP) and beta-endorphin (beta-EP) by radioimmunoassay.
      Subsequently, rats were perfused transcardially and the brain tissues containing
      the trigeminal nucleus caudalis (TNC) were achieved for detecting the number of
      Fos-immunoreactive cells by immunohistochemical method. RESULTS: In the mice
      experiments, compared with the normal control group, high- and medium-dose of QTG
      groups significantly raised the pain threshold (P<0.01), reduced the number of
      writhing response (P<0.01) and spontaneous activity (P<0.01), but had no
      influence on the sleeping rate of mice (P>0.05), and low-dose of QTG group also
      raised the pain threshold at 120 min (P=0.007), as well as lowered locomotor
      activity of mice at 2 h (P=0.003). On the study of migraine model rats, high- and
      medium-dose of QTG groups remarkably down-regulated the levels of plasma CGRP
      (P<0.01), up-regulated the levels of plasma beta-EP (P<0.01) and inhibited the
      expression of Fos protein in TNC (P<0.01), compared with the model group.
      CONCLUSIONS: QTG has obvious analgesic and sedative action and its mechanism on
      relieving migraine may be through regulating the levels of neurotransmitters
      and/or neuropeptides, and inhibiting the activation of Fos pathway.

PMID- 24740553
TI  - Inhibitory effect of cryptotanshinone on angiogenesis and Wnt/beta-catenin
      signaling pathway in human umbilical vein endothelial cells.
AB  - OBJECTIVE: To investigate the anti-angiogenic effect of cryptotanshinone (CPT) on
      human umbilical vein endothelial cells (HUVECs) and the effect of CPT on Wnt/beta
      catenin signaling pathway. METHODS: HUVECs were incubated with 0, 2.5, 5, 10, and
      20 MU mol/L CPT for detecting cell viability with dimethyl thiazolyl-2,5
      diphenyltetrazolium bromide (MTT) assay. Then, HUVECs were incubated with 0, 2.5,
      5, and 10 MU mol/L CPT for detecting endothelial cell migration, invasion, and
      tubular-like structure formation with wound healing, transwell invasion and
      matrigel tube formation assays, respectively. To gain insight into CPT-mediated
      signaling, the effects of CPT on T-cell factor/lymphocyte enhancer factor
      (TCF/LEF) transcription factors were detected by the Dual-luciferase reporter
      assay. Next, the nuclear expression of beta-catenin was evaluated using Western
      blot and immunochemistry. Finally, vascular endothelial growth factor (VEGF) and
      cyclin D1, downstream proteins of the Wnt pathway were examined with Western
      blot. RESULTS: CPT dose-dependently suppressed endothelial cell viability,
      migration, invasion, and tubular-like structure formation. In particular, CPT
      blocked beta-catenindependent transcription in HUVECs in a dose-dependent manner.
      In Western bolt, 10 MU mol/L CPT decreased expression of beta-catenin in nucleus
      of HUVECs (P<0.01). In immunohistochemistry, beta-catenin was more potent in
      response to LiCl (an activator of the pathway) treatment. However, the signals
      were weaker in the nucleus of the CPT (10 MU mol/L) group, compared to the
      positive control. Also, VEGF and cyclin D1 were both eliminated by CPT in 5 and
      10 MU mol/L doses (P<0.05). CONCLUSION: Our study supported the role of CPT as an
      angiogenic inhibitor, which may impact on the Wnt/beta-catenin signaling pathway.

PMID- 24740555
TI  - Family member accompaniment to routine medical visits is associated with better
      self-care in heart failure patients.
AB  - OBJECTIVES: To examine the association between frequency of family member
      accompaniment to medical visits and heart failure (HF) self-care maintenance and
      management and to determine whether associations are mediated through
      satisfaction with provider communication. METHODS: Cross-sectional survey of 150
      HF patients seen in outpatient clinics. HF self-care maintenance and management
      were assessed using the Self-Care of Heart Failure Index. Satisfaction with
      provider communication was assessed using a single question originally included
      in the American Board of Internal Medicine Patient Satisfaction Questionnaire.
      Frequency of family member accompaniment to visits was assessed using a single
      item question. We performed regression analyses to examine associations between
      frequency of accompaniment and outcomes. Mediation analysis was conducted using
      MacKinnon's criteria. RESULTS: Overall, 61% reported accompaniment by family
      members to some/most/every visit. Accompaniment to some/most/every visit was
      associated with higher self-care maintenance (beta = 6.4, SE 2.5; p = 0.01) and
      management (beta = 12.7, SE 4.9; p = 0.01) scores. Satisfaction with provider
      communication may mediate the association between greater frequency of
      accompaniment to visits and self-care maintenance (1.092; p = 0.06) and self-care
      management (1.428; p = 0.13). DISCUSSION: Accompaniment to medical visits is
      associated with better HF self-care maintenance and management, and this effect
      may be mediated through satisfaction with provider communication.

PMID- 24740556
TI  - Structural analysis of lipopolysaccharide produced by Heddleston serovars 10, 11,
      12 and 15 and the identification of a new Pasteurella multocida
      lipopolysaccharide outer core biosynthesis locus, L6.
AB  - Pasteurella multocida is a Gram-negative bacterial pathogen classified into 16
      serovars based on lipopolysaccharide (LPS) antigens. Previously, we have
      characterized the LPS outer core biosynthesis loci L1, L2, L3, L5 and L7, and
      have elucidated the full range of LPS structures associated with each. In this
      study, we have determined the LPS structures produced by the type strains
      representing the serovars 10, 11, 12 and 15 and characterized a new LPS outer
      core biosynthesis locus, L6, common to all. The L6 outer core biosynthesis locus
      shares significant synteny with the L3 locus but due to nucleotide divergence,
      gene duplication and gene redundancy, the L6 and L3 LPS outer cores are
      structurally distinct. Using LPS structural and genetic differences identified in
      each L6 strain, we have predicted a role for most of the L6 glycosyltransferases
      in LPS assembly. Importantly, we have identified two glycosyltransferases, GctD
      and GatB, that differ by one amino acid, A162T, but use different donor sugars
      [uridine diphosphate (UDP)-Glc and UDP-Gal, respectively]. The longest outer core
      oligosaccharide, produced by the serovar 12 type strain, contained a terminal
      region consisting of beta-Gal-(1,4)-beta-GlcNAc-(1,3)-beta-Gal-(1,4)-beta-Glc
      that was identical in structure to the vertebrate glycosphingolipid,
      paragloboside. Mimicry of host glycosphingolipids has been observed previously in
      P. multocida strains belonging to L3 LPS genotype, which produce LPS similar in
      structure to the globo-series of glycosphingolipids. The expression of a
      paragloboside-like oligosaccharide on the LPS produced by the serovar 12 type
      strain indicates that strains belonging to the L6 LPS genotype may also engage in
      molecular mimicry. 

PMID- 24740557
TI  - Preoperative risk stratification for cancer-specific survival of patients with
      upper urinary tract urothelial carcinoma treated by nephroureterectomy.
AB  - BACKGROUND: This study aimed to identify preoperative parameters for predicting
      cancer-specific survival (CSS) in patients with upper urinary tract urothelial
      carcinoma (UTUC) who have undergone radical nephroureterectomy (RNU). METHODS:
      The preoperative clinical and laboratory records of 357 UTUC patients who
      underwent RNU at three different institutions were retrospectively reviewed (256,
      training set; 101, test set). Univariate and multivariate analyses were performed
      on the training set data to identify preoperative prognostic factors, using which
      a risk stratification model was developed. The model was validated using test set
      data. RESULTS: In univariate analysis, clinical T stage classification and
      preoperative concentrations of hemoglobin, C-reactive protein, sodium, and
      albumin showed significant association with CSS. Multivariate analysis showed
      that low preoperative sodium and hemoglobin concentrations were significantly
      associated with a poor prognosis. A risk stratification model was developed using
      the preoperative sodium (<141 mEq/L) and hemoglobin concentrations (below
      normal). Three subgroups were formed depending on the presence of no (favorable
      group), one (intermediate), or two (poor) prognostic factors, and the 5-year CSS
      estimates were found to be 96.5, 75.5, and 47.0 %, respectively (P < 0.01). The
      risk model was significantly associated with the adverse pathological findings of
      stage pT3 or more and lymphovascular invasion (P = 0.005). CONCLUSION: We
      identified low preoperative sodium and hemoglobin concentrations as prognostic
      factors for patients with UTUC treated with RNU. Our risk stratification model
      may help physicians design a therapeutic strategy.

PMID- 24740558
TI  - Vascular and extravascular findings on magnetic resonance angiography of the
      thoracic aorta and the origin of the great vessels.
AB  - PURPOSE: To investigate the presence of relevant vascular and incidental
      extravascular findings in patients undergoing magnetic resonance angiography
      (MRA) of the thoracic aorta and origin of the great vessels. MATERIALS AND
      METHODS: In all, 165 consecutive patients (mean age 61 +/- 12 years) underwent
      1.5 T MRA of the thorax. Two researchers identified vascular and incidental
      extravascular findings. Clinically relevant vascular findings were defined.
      Extravascular findings were categorized as minor (Group A, without change in
      patient treatment), intermediate (Group B, unclear clinical relevance, requiring
      additional investigations), and major (Group C, causing a change in patient
      treatment). RESULTS: A total of 306 relevant vascular findings were found in our
      cohort. A total of 397 extravascular findings were observed among the patients
      and were classified as Group A findings in 81.9% (325/397 findings, observed in
      146 of 165 patients), as Group B findings in 15.4% (61/397 findings, observed in
      52 of 165 patients), and as Group C in 2.8% of findings (11/397). The clinically
      relevant Group C findings were observed in 6.7% of patients (11/165), comprising
      eight previously unknown neoplasms (4.8% of 165), two patients with
      hemodynamically relevant pericardial effusion (1.2% of 165), and one patient with
      spondylodiscitis (0.6% of 165) detected by MRA. CONCLUSION: Relevant vascular and
      extravascular findings were found in patients referred for thoracic MRA. Most
      extravascular findings can be categorized by MRA as minor, while others required
      further diagnostics since they may be malignant or otherwise clinically relevant.

PMID- 24740559
TI  - Electrospun nanofiber scaffolds and plasma polymerization: a promising
      combination towards complete, stable endothelial lining for vascular grafts.
AB  - In the quest to reduce risk of thrombosis in vascular grafts, it is essential to
      provide a surface with morphological and mechanical properties close to those of
      the extracellular matrix beneath the luminal endothelium, and to favor the growth
      of a confluent, stable monolayer of endothelial cells. This is accomplished here
      by combining electrospun poly(ethylene terephthalate) (PET) mats with an amine
      rich thin plasma-polymerized coating, designated "L-PPE:N." Its deposition does
      not modify the open, highly porous mats and leads only to small changes in
      mechanical properties. L-PPE:N significantly improves the adhesion and growth of
      human umbilical vein endothelial cells (HUVEC) and their resistance to flow
      induced shear stress. These properties favor the formation of desired confluent
      HUVEC monolayers on the topmost surface, unlike conventional vascular grafts
      (ePTFE or woven PET), where cells migrate inside the material. This combination
      is therefore highly advantageous for the pre-endothelialization of the luminal
      side of small-diameter vascular prostheses. 

PMID- 24740560
TI  - The mechanisms of 5-FU-PLA-O-CMC-NPS-mediated inhibition of the proliferation of
      colorectal cancer cell line SW480.
AB  - We aimed to investigate how 5-FU-PLA-O-CMC-NP (5-FPOCN) inhibits the
      proliferation of the SW480 colon cancer cell line. Following the treatment of
      cell line SW480 with 0.1, 1, 10 or 100 MUg/ml 5-FPOCN or 5-fluorouracil
      (fluorouracil, 5-Fu) for 0, 24, 48, or 72, the rate of cell was tested by the
      tetrazolium assay (MTT). After the SW480 cells were treated with 5-FPOCN or 5-FU
      for 72 h, the growth rate and apoptosis were detected. After the SW480 cells were
      treated with 5-FPOCN or 5-FU for 24, 48, 72, or 120, flow cytometry (FCM) was
      used to determine the cell cycle distribution. The changes in the expression of
      P21, CyclinD1 and Rb were detected by Western blotting and real-time PCR. We
      found that different doses of 5-FPOCN can significantly inhibit the growth rate
      of SW480 cells, and this effect is dose and time dependent. However, there is no
      significant difference from 72 to 120 h (P>0.05). After 5-FPOCN treatment for 72
      h, there is a negative correlation between the concentration of 5-FPOCN and the
      activity of SW480 cells and a positive correlation between the concentration of 5
      FPOCN and SW480 cell apoptosis. G1 phase was significantly increased, and S phase
      was significantly decreased in 5-FPOCN-treated SW480 cells at 72 h compared to
      the control group (P<0.05); there was a positive correlation between the
      concentration of 5-FPOCN and the above changes. It was suggested that 5-FPOCN can
      delay G1/S phase and that this is a dose-dependent effect. The expression of P21
      protein and messenger RNA (mRNA) and Rb protein and mRNA was significantly
      increased in 5-FPOCN-treated SW480 cells at 72 h compared to the control group,
      and this was a dose- and time-dependent effect. CyclinD1 protein and mRNA
      expression was reduced as the dose increased, and its expression was negatively
      associated with the increased expression of P21. We concluded that 5-FPOCN can
      significantly inhibit the growth of colon cancer SW480 cells. 5-FPOCN increased
      P21 expression and decreased cyclin family and pRb expression to promote cell
      cycle delay and apoptosis.

PMID- 24740561
TI  - May increased CA125 in borderline ovarian tumor be indicative of a poor
      prognosis? A case report.
AB  - We present a case of a 58-year-old menopausal woman referred to our hospital for
      the presence of large pelvic masses diagnosed by clinical examination and pelvic
      ultrasound. MRI examination showed voluminous bilateral capsulated multilocular
      ovarian cysts slightly hyperintense on T1-weighted images with thick septa and
      small papillary projections. CT scan confirmed the MRI findings. Among the
      ovarian tumor markers analyzed (CA125, HE4, and CA72.4), only Ca125 was slightly
      increased (48 U/ml). These data were suggestive of mucinous ovarian tumor. The
      patient underwent total hysterectomy with bilateral salpingo-oophorectomy,
      appendectomy, and multiple peritoneal biopsies. Pathological examination revealed
      bilateral borderline mucinous ovarian tumor with superficial atypical implants.
      Nine months later, the patient complained of left coxofemoral pain and underwent
      a PET/TC total body that suggested pubic bone metastases. Ovarian tumor markers
      were analyzed, and a second PET/TC was performed. CA125 was 252 U/ml, HE4 62
      pM/L, and CA72.4 > 100 U/Ml. PET/TC was suggestive of peritoneal carcinosis. The
      patient was readmitted to the hospital. Clinical examination revealed small
      vaginal nodules. All nodules were excised. Microscopic analysis of all specimens
      revealed metastatic mucinous adenocarcinoma of intestinal type.The case shows
      that even a slight CA125 increase in the presence of a borderline ovarian tumor
      should not be overlooked since it can be indicative of a progressive disease.
      This case also highlights its additional diagnostic value when serum CA125
      analysis is used in conjunction with MRI and CT imaging for the prognosis of
      mucinous borderline ovarian tumors (mBOTs).

PMID- 24740562
TI  - MDM2 SNP309 and risk of cervical cancer.

PMID- 24740563
TI  - Association of a genetic variant in microRNA-146a with risk of colorectal cancer:
      a population-based case-control study.
AB  - MicroRNAs (miRNAs) are small non-coding RNAs that negatively regulate target gene
      expression at the posttranscriptional level. Although recent studies have
      indicated that miR-146a is involved in the tumorigenesis of various types of
      malignancies, few studies have investigated its role in colorectal cancer. In the
      current study, we examined the expression of miR-146a in colorectal cancer tissue
      and adjacent normal controls using publicly available expression profiling data.
      We then conducted a population-based case-control study which included 554
      colorectal cancer cases and 566 matched healthy controls to assess the
      association of a genetic variant (rs2910164) in miR-146a with colorectal cancer
      susceptibility. We observed decreased expression of miR-146a in rectal cancer
      tissue compared with adjacent normal controls (P < 0.001). Association between
      miR-146a rs2910164 polymorphism and risk of colorectal cancer was detected with
      effect modification by alcohol drinking status (P for interaction = 0.010). Among
      non-alcohol drinkers, individuals with CC/CG genotype had an increased risk of
      developing colorectal cancer compared with those carrying GG genotype (odds ratio
      (OR) = 1.63, 95 % confidence interval (CI): 1.07 ~ 2.47). Our findings indicate
      an association between miR-146a dysregulation and colorectal cancer, and suggest
      that miR-146a may play a role in colorectal carcinogenesis. Further large
      population-based prospective studies as well as mechanistic investigations are
      warranted to validate our findings.

PMID- 24740564
TI  - High serum transforming growth factor beta 1 (TGFB1) level predicts better
      survival in breast cancer.
AB  - The transforming growth factor beta 1 (TGFB1) is a regulatory cytokine with both
      tumor suppressor and tumor-promoting effects in breast cancer (BC) cell lines and
      tissue. Data about level of circulating TGFB1 and its prognostic significance in
      BC patients is conflicting. The objective of this study is to determine the
      clinical significance of the serum TGFB1 levels in BC patients. We enrolled 96
      female patients with histopathologically diagnosed BC who did not receive
      chemotherapy (CT) or radiotherapy. Serum TGFB1 levels were measured by ELISA
      method and compared with 30 healthy controls. The mean serum TGFB1 level of BC
      patients was significantly higher than controls (0.08 vs. 0.04 ng/ml, p < 0.001).
      There was no significant difference according to known disease-related
      clinicopathological or laboratory parameters. Serum TGFB1 level had a significant
      impact on overall survival in both univariate (p = 0.01) and multivariate
      analysis (p = 0.013). Serum TGFB1 level is elevated in BC patients and has a
      favorable prognostic value. However, it has no predictive role on CT response.

PMID- 24740565
TI  - MicroRNA-195 regulates steroid receptor coactivator-3 protein expression in
      hepatocellular carcinoma cells.
AB  - Multiple studies have shown that steroid receptor coactivator-3 (SRC-3) is
      upregulated and promotes cell proliferation in several human cancers, including
      breast, lung, and prostate carcinoma. However, its molecular determinants remain
      largely unexplored. In the current study, by way of informatics software, we
      found that MicroRNA-195 (miR-195) could negatively regulate protein levels of SRC
      3 through targeting its 3'-untranslated region (3'-UTR) in hepatocellular
      carcinoma (HCC) cells. As a result, miR-195 mimics inhibited while its antisense
      enhanced SRC-3 protein levels. Furthermore, miR-195 could modulate cell
      proliferation and tumor growth in vivo and in vitro. Therefore, our results
      demonstrate a novel molecular mechanism for the dysregulated expression of SRC-3
      in hepatocellular carcinoma. 

PMID- 24740566
TI  - SPAG9 is overexpressed in human prostate cancer and promotes cancer cell
      proliferation.
AB  - Sperm-associated antigen 9 (SPAG9) was recently reported to be overexpressed in
      several cancers and associated with the malignant behavior of cancer cells.
      However, the expression pattern of SPAG9 and its clinical significance in human
      prostate cancer have not been reported. In the present study, we analyzed SPAG9
      expression in human prostate cancer tissues by immunohistochemistry and found
      that SPAG9 was overexpressed in 36.5 % of prostate cancer specimens. There was a
      significant association between SPAG9 overexpression and tumor stage (p = 0.0020)
      and Gleason score (p = 0.0377). Transfection of SPAG9 plasmid was performed in PC
      3 cell line and siRNA knockdown was carried out in DU145 cells. Colony formation
      and MTT showed that SPAG9 overexpression promoted while siRNA knockdown inhibited
      prostate cancer cell proliferation. In addition, we found that SPAG9 could
      regulate cyclin D1 and cyclin E protein expression. In conclusion, SPAG9 is
      overexpressed in human prostate cancers and contributes to prostate cancer cell
      growth, possibly through cyclin protein regulation.

PMID- 24740567
TI  - Multifunctionality in bimetallic Ln(III)[W(V)(CN)8]3- (Ln = Gd, Nd) coordination
      helices: optical activity, luminescence, and magnetic coupling.
AB  - Two chiral luminescent derivatives of pyridine bis(oxazoline) (Pybox), (SS/RR)
      iPr-Pybox (2,6-bis[4-isopropyl-2-oxazolin-2-yl]pyridine) and (SRSR/RSRS)-Ind
      Pybox (2,6-bis[8H-indeno[1,2-d]oxazolin-2-yl]pyridine), have been combined with
      lanthanide ions (Gd(3+), Nd(3+)) and octacyanotungstate(V) metalloligand to
      afford a remarkable series of eight bimetallic CN(-)-bridged coordination chains:
      {[Ln(III)(SS/RR-iPr-Pybox)(dmf)4]3[W(V)(CN)8]3}n ?dmf?4 H2O (Ln = Gd, 1-SS and 1
      RR; Ln = Nd, 2-SS and 2-RR) and {[Ln(III)(SRSR/RSRS-Ind
      Pybox)(dmf)4][W(V)(CN)8]}n?5 MeCN?4 MeOH (Ln = Gd, 3-SRSR and 3-RSRS; Ln = Nd, 4
      SRSR and 4-RSRS). These materials display enantiopure structural helicity, which
      results in strong optical activity in the range 200-450 nm, as confirmed by
      natural circular dichroism (NCD) spectra and the corresponding UV/Vis absorption
      spectra. Under irradiation with UV light, the Gd(III)-W(V) chains show dominant
      ligand-based red phosphorescence, with lambdamax ~660 nm for 1-(SS/RR) and 680 nm
      for 3-(SRSR/RSRS). The Nd(III)-W(V) chains, 2-(SS/RR) and 4-(SRSR/RSRS), exhibit
      near-infrared luminescence with sharp lines at 986, 1066, and 1340 nm derived
      from intra-f (4)F3/2 -> (4)I9/2,11/2,13/2 transitions of the Nd(III) centers.
      This emission is realized through efficient ligand-to-metal energy transfer from
      the Pybox derivative to the lanthanide ion. Due to the presence of paramagnetic
      lanthanide(III) and [W(V)(CN)8](3-) moieties connected by cyanide bridges, 1
      (SS/RR) and 3-(SRSR/RSRS) are ferrimagnetic spin chains originating from
      antiferromagnetic coupling between Gd(III) (SGd = 7/2) and W(V) (SW = 1/2)
      centers with J1-(SS) = -0.96(1) cm(-1), J1-(RR) =-0.95(1) cm(-1), J3-(SRSR) = 
      0.91(1) cm(-1), and J3-(RSRS) =-0.94(1) cm(-1). 2-(SS/RR) and 4-(SRSR/RSRS)
      display ferromagnetic coupling within their Nd(III)-NC-W(V) linkages.

PMID- 24740568
TI  - Derivative of bardoxolone methyl, dh404, in an inverse dose-dependent manner
      lessens diabetes-associated atherosclerosis and improves diabetic kidney disease.
AB  - Oxidative stress and inflammation are inextricably linked and play essential
      roles in the initiation and progression of diabetes complications such as
      diabetes-associated atherosclerosis and nephropathy. Bolstering antioxidant
      defenses is an important mechanism to lessen oxidative stress and inflammation.
      In this study, we have used a novel analog of the NFE2-related factor 2 (Nrf2)
      agonist bardoxolone methyl, dh404, to investigate its effects on diabetic
      macrovascular and renal injury in streptozotocin-induced diabetic apolipoprotein
      E(-/-) mice. We show that dh404, at lower but not higher doses, significantly
      lessens diabetes-associated atherosclerosis with reductions in oxidative stress
      (in plasma, urine, and vascular tissue) and proinflammatory mediators tumor
      necrosis factor-alpha, intracellular adhesion molecule-1, vascular cell adhesion
      molecule-1, and monocyte chemotactic protein-1 (MCP-1). We demonstrate that dh404
      attenuates functional (urinary albumin-to-creatinine ratio) and structural
      (mesangial expansion) glomerular injury and improves renal tubular injury. Liver
      functional and structural studies showed that dh404 is well tolerated.
      Complementary in vitro studies in normal rat kidney cells showed that dh404
      significantly upregulates Nrf2-responsive genes, heme oxygenase-1, NAD(P)H
      quinone oxidoreductase 1, and glutathione-S transferase, with inhibition of
      transforming growth factor-beta-mediated profibrotic fibronectin, collagen I, and
      proinflammatory interleukin-6. Higher doses of dh404 were associated with
      increased expression of proinflammatory mediators MCP-1 and nuclear factor
      kappaB. These findings suggest that this class of compound is worthy of further
      study to lessen diabetes complications but that dosage needs consideration. 

PMID- 24740570
TI  - Pancreatic beta-cell failure mediated by mTORC1 hyperactivity and autophagic
      impairment.
AB  - Hyperactivation of the mammalian target of rapamycin complex 1 (mTORC1) in beta
      cells is usually found as a consequence of increased metabolic load. Although it
      plays an essential role in beta-cell compensatory mechanisms, mTORC1 negatively
      regulates autophagy. Using a mouse model with beta-cell-specific deletion of Tsc2
      (betaTsc2(-/-)) and, consequently, mTORC1 hyperactivation, we focused on the role
      that chronic mTORC1 hyperactivation might have on beta-cell failure. mTORC1
      hyperactivation drove an early increase in beta-cell mass that later declined,
      triggering hyperglycemia. Apoptosis and endoplasmic reticulum stress markers were
      found in islets of older betaTsc2(-/-) mice as well as accumulation of p62/SQSTM1
      and an impaired autophagic response. Mitochondrial mass was increased in beta
      cells of betaTsc2(-/-) mice, but mitophagy was also impaired under these
      circumstances. We provide evidence of beta-cell autophagy impairment as a link
      between mTORC1 hyperactivation and mitochondrial dysfunction that probably
      contributes to beta-cell failure.

PMID- 24740569
TI  - ADCY5 couples glucose to insulin secretion in human islets.
AB  - Single nucleotide polymorphisms (SNPs) within the ADCY5 gene, encoding adenylate
      cyclase 5, are associated with elevated fasting glucose and increased type 2
      diabetes (T2D) risk. Despite this, the mechanisms underlying the effects of these
      polymorphic variants at the level of pancreatic beta-cells remain unclear. Here,
      we show firstly that ADCY5 mRNA expression in islets is lowered by the possession
      of risk alleles at rs11708067. Next, we demonstrate that ADCY5 is indispensable
      for coupling glucose, but not GLP-1, to insulin secretion in human islets.
      Assessed by in situ imaging of recombinant probes, ADCY5 silencing impaired
      glucose-induced cAMP increases and blocked glucose metabolism toward ATP at
      concentrations of the sugar >8 mmol/L. However, calcium transient generation and
      functional connectivity between individual human beta-cells were sharply
      inhibited at all glucose concentrations tested, implying additional, metabolism
      independent roles for ADCY5. In contrast, calcium rises were unaffected in ADCY5
      depleted islets exposed to GLP-1. Alterations in beta-cell ADCY5 expression and
      impaired glucose signaling thus provide a likely route through which ADCY5 gene
      polymorphisms influence fasting glucose levels and T2D risk, while exerting more
      minor effects on incretin action.

PMID- 24740571
TI  - Insulin resistance is associated with diminished endoplasmic reticulum stress
      responses in adipose tissue of healthy and diabetic subjects.
AB  - We recently showed that insulin increased ER stress in human adipose tissue. The
      effect of insulin resistance on ER stress is not known. It could be decreased,
      unchanged, or increased, depending on whether insulin regulates ER stress via the
      metabolic/phosphoinositide 3-kinase (PI3K) or alternate signaling pathways. To
      address this question, we examined effects of lipid-induced insulin resistance on
      insulin stimulation of ER stress. mRNAs of several ER stress markers were
      determined in fat biopsies obtained before and after 8-h hyperglycemic
      hyperinsulinemic clamping in 13 normal subjects and in 6 chronically insulin
      resistant patients with type 2 diabetes mellitus (T2DM). In normal subjects,
      hyperglycemia-hyperinsulinemia increased after/before mRNA ratios of several ER
      stress markers (determined by ER stress pathway array and by individual RT-PCR).
      Lipid infusion was associated with inhibition of the PI3K insulin-signaling
      pathway and with a decrease of hyperinsulinemia-induced ER stress responses. In
      chronically insulin-resistant patients with T2DM, hyperglycemic-hyperinsulinemia
      did not increase ER stress response marker mRNAs. In summary, insulin resistance,
      either produced by lipid infusions in normal subjects or chronically present in
      T2DM patients, was associated with decreased hyperinsulinemia-induced ER stress
      responses. This suggests, but does not prove, that these two phenomena were
      causally related.

PMID- 24740572
TI  - Diabetes irreversibly depletes bone marrow-derived mesenchymal progenitor cell
      subpopulations.
AB  - Diabetic vascular pathology is largely attributable to impairments in tissue
      recovery from hypoxia. Circulating progenitor cells have been postulated to play
      a role in ischemic recovery, and deficiencies in these cells have been well
      described in diabetic patients. Here, we examine bone marrow-derived mesenchymal
      progenitor cells (BM-MPCs) that have previously been shown to be important for
      new blood vessel formation and demonstrate significant deficits in the context of
      diabetes. Further, we determine that this dysfunction is attributable to
      intrinsic defects in diabetic BM-MPCs that are not correctable by restoring
      glucose homeostasis. We identify two transcriptionally distinct subpopulations
      that are selectively depleted by both type 1 and type 2 diabetes, and these
      subpopulations have provasculogenic expression profiles, suggesting that they are
      vascular progenitor cells. These results suggest that the clinically observed
      deficits in progenitor cells may be attributable to selective and irreversible
      depletion of progenitor cell subsets in patients with diabetes.

PMID- 24740573
TI  - mTORC1-independent reduction of retinal protein synthesis in type 1 diabetes.
AB  - Poorly controlled diabetes has long been known as a catabolic disorder with
      profound loss of muscle and fat body mass resulting from a simultaneous reduction
      in protein synthesis and enhanced protein degradation. By contrast, retinal
      structure is largely maintained during diabetes despite reduced Akt activity and
      increased rate of cell death. Therefore, we hypothesized that retinal protein
      turnover is regulated differently than in other insulin-sensitive tissues, such
      as skeletal muscle. Ins2(Akita) diabetic mice and streptozotocin-induced diabetic
      rats exhibited marked reductions in retinal protein synthesis matched by a
      concomitant reduction in retinal protein degradation associated with preserved
      retinal mass and protein content. The reduction in protein synthesis depended on
      both hyperglycemia and insulin deficiency, but protein degradation was only
      reversed by normalization of hyperglycemia. The reduction in protein synthesis
      was associated with diminished protein translation efficiency but, surprisingly,
      not with reduced activity of the mTORC1/S6K1/4E-BP1 pathway. Instead, diabetes
      induced a specific reduction of mTORC2 complex activity. These findings reveal
      distinctive responses of diabetes-induced retinal protein turnover compared with
      muscle and liver that may provide a new means to ameliorate diabetic retinopathy.

PMID- 24740575
TI  - Dietary fiber and phenolic compounds as functional ingredients: interaction and
      possible effect after ingestion.
AB  - Dietary fiber and phenolic compounds are two recognized dietary factors
      responsible for potential effects on human health; therefore, they have been
      widely used to increase functionality of some foods. This paper focuses on
      showing the use of both substances as functional ingredients for enriching foods,
      and at the same time, describes the use of a single material that combines the
      properties of the two types of substances. The last part of the work describes
      some facts related to the interaction between dietary fiber and phenolic
      compounds, which could affect the bioaccessibility and absorption of phenolics in
      the gut. In this sense, the purpose of the present review is to compile and
      analyze evidence relating to the use of dietary fiber and phenolic compounds to
      enhance technological and nutritional properties of foods and hypothesize some of
      the possible effects in the gut after their ingestion. 

PMID- 24740574
TI  - The rate of fall of blood glucose determines the necessity of forebrain
      projecting catecholaminergic neurons for male rat sympathoadrenal responses.
AB  - Different onset rates of insulin-induced hypoglycemia use distinct glucosensors
      to activate sympathoadrenal counterregulatory responses (CRRs). Glucosensory
      elements in the portal-mesenteric veins are dispensable with faster rates when
      brain elements predominate, but are essential for responses to the slower-onset
      hypoglycemia that is common with insulin therapy. Whether a similar rate
      associated divergence exists within more expansive brain networks is unknown.
      Hindbrain catecholamine neurons distribute glycemia-related information
      throughout the forebrain. We tested in male rats whether catecholaminergic
      neurons that project to the medial and ventromedial hypothalamus are required for
      sympathoadrenal CRRs to rapid- and slow-onset hypoglycemia and whether these
      neurons are differentially engaged as onset rates change. Using a catecholamine
      specific neurotoxin and hyperinsulinemic-hypoglycemic clamps, we found that
      sympathoadrenal CRRs to slow- but not rapid-onset hypoglycemia require
      hypothalamus-projecting catecholaminergic neurons, the majority of which
      originate in the ventrolateral medulla. As determined with Fos, these neurons are
      differentially activated by the two onset rates. We conclude that 1)
      catecholaminergic projections to the hypothalamus provide essential information
      for activating sympathoadrenal CRRs to slow- but not rapid-onset hypoglycemia, 2)
      hypoglycemia onset rates have a major impact on the hypothalamic mechanisms that
      enable sympathoadrenal CRRs, and 3) hypoglycemia-related sensory information
      activates hindbrain catecholaminergic neurons in a rate-dependent manner. 

PMID- 24740576
TI  - Influences of primary cilia on cortical morphogenesis and neuronal subtype
      maturation.
AB  - Recognition that virtually every neuronal progenitor cell and neuron in the
      cerebral cortex is ciliated has triggered intense interest in neuronal cilia
      function. Here, we review recent studies that suggest the primary cilia of
      cortical progenitor cells are required for establishing and maintaining the
      organization within pools of proliferative cells. In addition, signaling via
      primary cilia differentially influence the migration and differentiation of
      excitatory and inhibitory neurons in the developing cortex. Specifically, the
      primary cilia of excitatory neurons appear to play a significant role in
      regulating the post-migratory differentiation of these neurons whereas cilia of
      inhibitory neurons appear to be required for the proper migration and positioning
      of those cells in cortex. Given the recently discovered functions of cilia in
      proliferation, neuronal migration, and differentiation, it is likely that further
      studies of cilia signaling will improve our understanding of how these basic
      developmental processes are regulated and may provide insight into how mutations
      in specific cilia genes linked to ciliopathies lead to the many neurological
      deficits associated with these diseases. 

PMID- 24740577
TI  - Do astrocytes collaborate with neurons in spreading the "infectious" abeta and
      Tau drivers of Alzheimer's disease?
AB  - Evidence has begun emerging for the "contagious" and destructive Abeta42 (amyloid
      beta42) oligomers and phosphorylated Tau oligomers as drivers of sporadic
      Alzheimer's disease (AD), which advances along a pathway starting from the
      brainstem or entorhinal cortex and leading to cognition-related upper cerebral
      cortex regions. Seemingly, Abeta42 oligomers trigger the events generating the
      neurotoxic Tau oligomers, which may even by themselves spread the characteristic
      AD neuropathology. It has been assumed that only neurons make and spread these
      toxic drivers, whereas their associated astrocytes are just janitorial
      bystanders/scavengers. But this view is likely to radically change since normal
      human astrocytes freshly isolated from adult cerebral cortex can be induced by
      exogenous Abeta25-35, an Abeta42 proxy, to make and secrete increased amounts of
      endogenous Abeta42. Thus, it would seem that the steady slow progression of AD
      neuropathology along specific cognition-relevant brain networks is driven by both
      Abeta42 and phosphorylated Tau oligomers that are variously released from
      increasing numbers of "contagion-stricken" members of tightly coupled neuron
      astrocyte teams. Hence, we surmise that stopping the oversecretion and spread of
      the two kinds of "contagious" oligomers by such team members, perhaps via a
      specific CaSR (Ca(2+)-sensing receptor) antagonist like NPS 2143, might
      effectively treat AD.

PMID- 24740578
TI  - Linear versus geometric morphometric approaches for the analysis of head shape
      dimorphism in lizards.
AB  - Differences between the sexes may arise because of differences in reproductive
      strategy, with females investing more in traits related to reproductive output
      and males investing more in traits related to resource holding capacity and
      territory defence. Sexual dimorphism is widespread in lizards and in many species
      males and females also differ in head shape. Males typically have bigger heads
      than females resulting in intersexual differences in bite force. Whereas most
      studies documenting differences in head dimensions between sexes use linear
      dimensions, the use of geometric morphometrics has been advocated as more
      appropriate to characterize such differences. This method may allow the
      characterization of local shape differences that may have functional
      consequences, and provides unbiased indicators of shape. Here, we explore whether
      the two approaches provide similar results in an analyses of head shape in
      Tupinambis merianae. The Argentine black and white tegu differs dramatically in
      body size, head size, and bite force between the sexes. However, whether the
      intersexual differences in bite force are simply the result of differences in
      head size or whether more subtle modifications (e.g., in muscle insertion areas)
      are involved remains currently unknown. Based on the crania and mandibles of 19
      lizards with known bite force, we show intersexual differences in the shape of
      the cranium and mandible using both linear and geometric morphometric approaches.
      Although both types of analyses showed generally similar results for the
      mandible, this was not the case for the cranium. Geometric morphometric
      approaches provided better insights into the underlying functional relationships
      between the cranium and the jaw musculature, as illustrated by shape differences
      in muscle insertion areas not detected using linear morphometric data.

PMID- 24740579
TI  - Rebuttal: Response to letter by Chugh S. Regarding "Best practices for
      transradial angiography and intervention: a consensus statement from the society
      for cardiovascular angiography and intervention's transradial working group".

PMID- 24740580
TI  - pH-dependent self-assembly of EAK16 peptides in the presence of a hydrophobic
      surface: coarse-grained molecular dynamics simulation.
AB  - Self-assembly behavior of the three types of ionic peptide, EAK16, is studied in
      the presence of a hydrophobic surface using coarse-grained molecular dynamics
      simulations at three pH ranges of the solution. It is found that the peptide
      chains of all the three types assemble on the hydrophobic surface. EAK16-I and
      EAK16-II peptides assemble into ribbon-like structures, regardless of the value
      of pH. EAK16-IV peptide chains, however, assemble into ribbon-like structures at
      low and high pH ranges and form disc-shaped assemblies on the hydrophobic surface
      at the isoelectric point, pH = 7. Strong intra-chain electrostatic interactions
      in the case of EAK16-IV peptide play the main role in dependence of its self
      assembly behavior on pH and the different morphology of its assembly relative to
      those of the two other types. Kinetics of growth of the assemblies on the
      hydrophobic surface is also studied. 

PMID- 24740581
TI  - Coil embolization of intracranial saccular aneurysms using the Low-profile
      Visualized Intraluminal Support (LVISTM) device.
AB  - INTRODUCTION: The novel Low-profile Visualized Intraluminal Support (LVISTM, LVIS
      and LVIS Jr.) device was recently introduced for stent-supported coil
      embolization of intracranial aneurysms. Periprocedural and midterm follow-up
      results for its use in stent-supported coil embolization of unruptured aneurysms
      are presented herein. METHODS: In this prospective multicenter study, clinical
      and radiologic outcomes were analyzed for 55 patients with saccular aneurysms
      undergoing LVIS-assisted coil embolization between October 2012 and February
      2013. Magnetic resonance angiography or digital subtraction angiography was
      performed to evaluate midterm follow-up results. RESULTS: The standard LVIS
      device, deployed in 27 patients, was more often used in internal carotid artery
      (ICA) aneurysms (n=19), whereas the LVIS Jr. (a lower profile stent, n=28) was
      generally reserved for anterior communicating artery (n=14) and middle cerebral
      artery (n=8) aneurysms. With LVIS-assisted coil embolization, successful
      occlusion was achieved in 45 aneurysms (81.8 %). Although no instances of
      navigation failure or stent malposition occurred, segmentally incomplete stent
      expansion was seen in five patients where the higher profile LVIS was applied to
      ICA including carotid siphon. Procedural morbidity was low (2/55, 3.6 %), limited
      to symptomatic thromboembolism. In the imaging of lesions (54/55, 98.2 %) at 6
      month follow-up, only a single instances of major recanalization (1.9 %)
      occurred. Follow-up angiography of 30 aneurysms (54.5 %) demonstrated in-stent
      stenosis in 26 (86.7 %), with no instances of stent migration. Only one patient
      suffered late delayed infarction (modified Rankin Scale 1). CONCLUSION: The LVIS
      device performed acceptably in stent-assisted coil embolization of non-ruptured
      aneurysms due to easy navigation and precise placement, although segmentally
      incomplete stent expansion and delayed in-stent stenosis were issues.

PMID- 24740582
TI  - Outcomes of matched sibling donor hematopoietic stem cell transplantation for
      severe sickle cell disease with myeloablative conditioning and intermediate-dose
      of rabbit anti-thymocyte globulin.
AB  - BACKGROUND: Allogeneic hematopoietic stem cell transplantation (HSCT) is a
      curative therapy for sickle cell disease (SCD) in children. Despite excellent
      outcomes of matched sibling donor (MSD) HSCT, there is still 5-10% chance of
      rejection and transplant related mortality (TRM) with 12-23% incidence of graft
      versus host disease (GVHD). We postulated that an intermediate dose of rabbit
      anti-thymocyte globulin (r-ATG, 10 mg/kg cumulative) would be effective in
      preventing both rejection and GVHD. PATIENTS AND METHODS: Fifteen patients,
      median age 5 (range 1.5-18) years, underwent MSD HSCT using busulfan (>= 12.8
      mg/kg with first dose pharmacokinetics), cyclophosphamide (total 200 mg/kg) and r
      ATG. Bone marrow was the stem cell source; tacrolimus and methotrexate were given
      for GVHD prophylaxis. RESULTS: All patients achieved donor engraftment and there
      was no TRM. One patient rejected donor cells at 2 months post-transplant.
      Majority of the patients had high and sustained level of donor chimerism. None of
      the patients developed >= Grade II GVHD. Incidence of CMV (10%) and EBV (9%)
      reactivations was low with rapid immune-reconstitution. Overall survival was 100%
      with event free survival of 93%. CONCLUSIONS: Eliminating the risks of TRM and
      GVHD by optimizing the regimen may lead to further acceptance of HSCT for SCD.

PMID- 24740583
TI  - Temperature-modulated water filtration using microgel-functionalized hollow-fiber
      membranes.
AB  - In the present work, we investigate the potential of aqueous polymer microgels in
      membrane technology, especially for filtration applications. The poly(N
      vinylcaprolactam)-based microgels exhibit thermoresponsive behavior and were
      employed to coat hollow-fiber membranes used for micro- and ultrafiltration. We
      discuss the preparation of microgel-modified membranes (by "inside-out" as well
      as "outside-in" filtration in dead-end mode). The clean-water permeability and
      stability of these membranes was studied not only as a function of time, but also
      of temperature. The microgel-modified membranes exhibit a reversible
      thermoresponsive behavior whereby both the resistance and the retention increased
      with decreasing temperature. 

PMID- 24740584
TI  - Rapid diagnostic tests versus clinical diagnosis for managing people with fever
      in malaria endemic settings.
AB  - BACKGROUND: In 2010, the World Health Organization recommended that all patients
      with suspected malaria are tested for malaria before treatment. In rural African
      settings light microscopy is often unavailable. Diagnosis has relied on detecting
      fever, and most people were given antimalarial drugs presumptively. Rapid
      diagnostic tests (RDTs) provide a point-of-care test that may improve management,
      particularly of people for whom the RDT excludes the diagnosis of malaria.
      OBJECTIVES: To evaluate whether introducing RDTs into algorithms for diagnosing
      and treating people with fever improves health outcomes, reduces antimalarial
      prescribing, and is safe, compared to algorithms using clinical diagnosis. SEARCH
      METHODS: We searched the Cochrane Infectious Disease Group Specialized Register;
      CENTRAL (The Cochrane Library); MEDLINE; EMBASE; CINAHL; LILACS; and the
      metaRegister of Controlled Trials for eligible trials up to 10 January 2014. We
      contacted researchers in the field and reviewed the reference lists of all
      included trials to identify any additional trials. SELECTION CRITERIA: Individual
      or cluster randomized trials (RCTs) comparing RDT-supported algorithms and
      algorithms using clinical diagnosis alone for diagnosing and treating people with
      fever living in malaria-endemic settings. DATA COLLECTION AND ANALYSIS: Two
      authors independently applied the inclusion criteria and extracted data. We
      combined data from individually and cluster RCTs using the generic inverse
      variance method. We presented all outcomes as risk ratios (RR) with 95%
      confidence intervals (CIs), and assessed the quality of evidence using the GRADE
      approach. MAIN RESULTS: We included seven trials, enrolling 17,505 people with
      fever or reported history of fever in this review; two individually randomized
      trials and five cluster randomized trials. All trials were conducted in rural
      African settings.In most trials the health workers diagnosing and treating
      malaria were nurses or clinical officers with less than one week of training in
      RDT supported diagnosis. Health worker prescribing adherence to RDT results was
      highly variable: the number of participants with a negative RDT result who
      received antimalarials ranged from 0% to 81%.Overall, RDT supported diagnosis had
      little or no effect on the number of participants remaining unwell at four to
      seven days after treatment (6990 participants, five trials, low quality
      evidence); but using RDTs reduced prescribing of antimalarials by up to three
      quarters (17,287 participants, seven trials, moderate quality evidence). As would
      be expected, the reduction in antimalarial prescriptions was highest where health
      workers adherence to the RDT result was high, and where the true prevalence of
      malaria was lower.Using RDTs to support diagnosis did not have a consistent
      effect on the prescription of antibiotics, with some trials showing higher
      antibiotic prescribing and some showing lower prescribing in the RDT group
      (13,573 participants, five trials, very low quality evidence).One trial reported
      malaria microscopy on all enrolled patients in an area of moderate endemicity, so
      we could compare the number of patients in the RDT and clinical diagnosis groups
      that actually had microscopy confirmed malaria infection but did not receive
      antimalarials. No difference was detected between the two diagnostic strategies
      (1280 participants, one trial, low quality evidence). AUTHORS' CONCLUSIONS:
      Algorithms incorporating RDTs can substantially reduce antimalarial prescribing
      if health workers adhere to the test results. Introducing RDTs has not been shown
      to improve health outcomes for patients, but adherence to the test result does
      not seem to result in worse clinical outcomes than presumptive
      treatment.Concentrating on improving the care of RDT negative patients could
      improve health outcomes in febrile children.

PMID- 24740585
TI  - The use of magnetic resonance imaging to examine ossification of the proximal
      tibial epiphysis for forensic age estimation in living individuals.
AB  - The establishment of radiation-free examination procedures in the field of
      forensic age diagnostics in living persons is to be considered of special
      scientific interest so as to minimize necessary exposure to X-rays while
      facilitating additional assessment of skeletal development in all cases. To this
      end, the advantages offered by magnetic resonance imaging in securing a practical
      application which is as unrestricted and complication-free as possible should be
      among the methods exploited in investigating such indicators of skeletal
      maturity. Within the framework of a retrospective study, we investigated the
      ossification status of the proximal tibial epiphysis on the MRI scans of 124
      females and 166 males aged between 10 and 30 years. All the images had been
      generated on a 3.0 T scanner using a T1-weighted turbo spin-echo sequence. When
      evaluating the ossification stage, a combination of modified classifications
      proposed by Schmeling et al. and by Kellinghaus et al. was used. The statistical
      evaluation included calculation of a variety of measures to describe specific
      ossification stages as well as kappa coefficients to assess intra- and inter
      observer agreement on diagnoses of individual stages. In forensic contexts,
      completion of the 14th year of life can be adequately evidenced in females with
      an ossification stage IV according to Schmeling et al. and in males with an
      ossification stage III c according to Kellinghaus et al. or an ossification stage
      IV according to Schmeling et al. In forensic contexts, the presence of an
      ossification stage IV according to Schmeling et al. can prove that the age of 16
      years has been exceeded only in the male sex, whereby for age estimation purposes
      the diagnosis should be in line with other skeletal maturity indicators. The
      results available displayed a high degree of intra- and inter-observer agreement.
      Examination of the ossification status of the proximal tibial epiphysis using
      magnetic resonance imaging represents an effective additional tool for use in
      radiation-free forensic age diagnostics in living persons. 

PMID- 24740587
TI  - Nitric oxide release triggered by two-photon excited photoluminescence of
      engineered nanomaterials.
AB  - A new strategy toward controllable release of NO for therapeutic purpose is
      described. Mn(2+)-doped ZnS quantum dots with NIR-II to visible upconversion
      properties were encapsulated by chitosan, with which photochemical NO precursors
      were conjugated to generate nanostructured materials capable of releasing NO
      under NIR-II irradiation. 

PMID- 24740586
TI  - Atypical cross talk between mentalizing and mirror neuron networks in autism
      spectrum disorder.
AB  - IMPORTANCE: Converging evidence indicates that brain abnormalities in autism
      spectrum disorder (ASD) involve atypical network connectivity, but it is unclear
      whether altered connectivity is especially prominent in brain networks that
      participate in social cognition. OBJECTIVE: To investigate whether adolescents
      with ASD show altered functional connectivity in 2 brain networks putatively
      impaired in ASD and involved in social processing, theory of mind (ToM) and
      mirror neuron system (MNS). DESIGN, SETTING, AND PARTICIPANTS: Cross-sectional
      study using resting-state functional magnetic resonance imaging involving 25
      adolescents with ASD between the ages of 11 and 18 years and 25 typically
      developing adolescents matched for age, handedness, and nonverbal IQ. MAIN
      OUTCOMES AND MEASURES: Statistical parametric maps testing the degree of whole
      brain functional connectivity and social functioning measures. RESULTS: Relative
      to typically developing controls, participants with ASD showed a mixed pattern of
      both over- and underconnectivity in the ToM network, which was associated with
      greater social impairment. Increased connectivity in the ASD group was detected
      primarily between the regions of the MNS and ToM, and was correlated with
      sociocommunicative measures, suggesting that excessive ToM-MNS cross talk might
      be associated with social impairment. In a secondary analysis comparing a subset
      of the 15 participants with ASD with the most severe symptomology and a tightly
      matched subset of 15 typically developing controls, participants with ASD showed
      exclusive overconnectivity effects in both ToM and MNS networks, which were also
      associated with greater social dysfunction. CONCLUSIONS AND RELEVANCE:
      Adolescents with ASD showed atypically increased functional connectivity
      involving the mentalizing and mirror neuron systems, largely reflecting greater
      cross talk between the 2. This finding is consistent with emerging evidence of
      reduced network segregation in ASD and challenges the prevailing theory of
      general long-distance underconnectivity in ASD. This excess ToM-MNS connectivity
      may reflect immature or aberrant developmental processes in 2 brain networks
      involved in understanding of others, a domain of impairment in ASD. Further,
      robust links with sociocommunicative symptoms of ASD implicate atypically
      increased ToM-MNS connectivity in social deficits observed in ASD.

PMID- 24740588
TI  - Consumption of a dark roast coffee decreases the level of spontaneous DNA strand
      breaks: a randomized controlled trial.
AB  - PURPOSE: Coffee consumption has been reported to decrease oxidative damage in
      peripheral white blood cells (WBC). However, effects on the level of spontaneous
      DNA strand breaks, a well established marker of health risk, have not been
      specifically reported yet. We analyzed the impact of consuming a dark roast
      coffee blend on the level of spontaneous DNA strand breaks. METHODS: Healthy men
      (n = 84) were randomized to consume daily for 4 weeks either 750 ml of fresh
      coffee brew or 750 ml of water, subsequent to a run in washout phase of 4 weeks.
      The study coffee was a blend providing high amounts of both caffeoylquinic acids
      (10.18 +/- 0.33 mg/g) and the roast product N-methylpyridinium (1.10 +/- 0.05
      mg/g). Before and after the coffee/water consumption phase, spontaneous strand
      breaks were determined by comet assay. RESULTS: At baseline, both groups
      exhibited a similar level of spontaneous DNA strand breaks. In the intervention
      phase, spontaneous DNA strand breaks slightly increased in the control (water
      only) group whereas they significantly decreased in the coffee group, leading to
      a 27% difference within both arms (p = 0.0002). Food frequency questionnaires
      indicated no differences in the overall diet between groups, and mean body weight
      during the intervention phases remained stable. The consumption of the study
      coffee substantially lowered the level of spontaneous DNA strand breaks in WBC.
      CONCLUSION: We conclude that regular coffee consumption contributes to DNA
      integrity.

PMID- 24740589
TI  - Can consumption of raw vegetables decrease the count of sister chromatid
      exchange? Results from a cross-sectional study in Krakow, Poland.
AB  - BACKGROUND: Sister chromatid exchange (SCE) is a widely used sensitive
      cytogenetic biomarker of exposure to genotoxic and cancerogenic agents. Results
      of human monitoring studies and cytogenetic damage have revealed that biological
      effects of genotoxic exposures are influenced by confounding factors related to
      life-style. Vegetable and fruit consumption may play a role, but available
      results are not consistent. The purpose of the study was to investigate the
      effect of consumption of raw and cooked vegetables and fruits on SCE frequency.
      METHODS: A total of 62 participants included colorectal cancer (CRC) patients,
      hospital-based controls and healthy laboratory workers. SCE frequency was
      assessed in blood lymphocytes. Frequency of vegetable and fruit consumption was
      gathered by structured semi-quantitative food frequency questionnaire. RESULTS:
      SCE frequency was lowest among hospital-based controls (4.4 +/- 1.1), a bit
      higher in CRC patients (4.5 +/- 1.0) and highest among laboratory workers (7.4 +/
      1.2) (p < 0.05). Multivariable linear regression showed a significant inverse
      effect (b = -0.20) of raw vegetable consumption, but not so for intake of cooked
      vegetables and fruits. CONCLUSIONS: The results of the study have shown the
      beneficial effect of consumption of raw vegetables on disrupted replication of
      DNA measured by SCE frequency, implying protection against genotoxic agents.
      Further effort is required to verify the role of cooked vegetables and fruits.

PMID- 24740590
TI  - Changes in the serum metabolite profile in obese children with weight loss.
AB  - PURPOSE: Childhood obesity is an increasing problem and is accompanied by
      metabolic disturbances. Recently, we have identified 14 serum metabolites by a
      metabolomics approach (FIA-MS/MS), which showed altered concentrations in obese
      children as compared to normal-weight children. Obese children demonstrated
      higher concentrations of two acylcarnitines and lower levels of three amino
      acids, six acyl-alkyl phosphatidylcholines, and three lysophosphatidylcholines.
      The aim of this study was to analyze whether these alterations normalize in
      weight loss. METHODS: We analyzed the changes of these 14 metabolites by the same
      metabolic kit as in our previous study in serum samples of 80 obese children with
      substantial weight loss (BMI-SDS reduction >0.5) and in 80 obese children with
      stable weight status all participating in a 1-year lifestyle intervention.
      RESULTS: In the children without weight change, no significant changes of
      metabolite concentrations could be observed. In children with substantial weight
      loss, glutamine, methionine, the lysophosphatidylcholines LPCaC18:1, LPCaC18:2,
      and LPCa20:4, as well as the acyl-alkyl phosphatidylcholine PCaeC36:2 increased
      significantly, while the acylcarnitines C12:1 and C16:1, proline, PCaeC34:1,
      PCaeC34:2, PCaeC34:3, PCaeC36:3, and PCaeC38:2 did not change significantly.
      CONCLUSIONS: The changes of glutamine, methionine, LPCaC18:1, LPCaC18:2,
      LPCa20:4, and PCaeC36:2 seem to be related to the changes of dieting or exercise
      habits in lifestyle intervention or to be a consequence of overweight since they
      normalized in weight loss. Further studies should substantiate our findings.

PMID- 24740591
TI  - Using operators to expand the block matrices forming the Hessian of a molecular
      potential.
AB  - We derive compact expressions of the second-order derivatives of bond length,
      bond angle, and proper and improper torsion angle potentials, in terms of
      operators represented in two orthonormal bases. Hereby, simple rules to generate
      the Hessian of an internal coordinate or a molecular potential can be formulated.
      The algorithms we provide can be implemented efficiently in high-level
      programming languages using vectorization. Finally, the method leads to compact
      expressions for a second-order expansion of an internal coordinate or a molecular
      potential.

PMID- 24740592
TI  - Therapeutic potential of different commercially available synbiotic on
      acetaminophen-induced uremic rats.
AB  - BACKGROUND: Currently kidney disease appears a foremost problem across the world.
      Acetaminophen is a commonly used antipyretic agent, which in high doses, causes
      uremia and used for experimentally induction of kidney disease. Bacteriotherapy
      affords a promising approach to mitigate uremic toxins by ingestion of urease
      positive bacteria, probiotics and symbiotic able to catabolize uremic solutes
      within the gut. The present study evaluates the effect of seven commercial
      symbiotic on kidney disease. METHODS: Fifty-four albino male rats were randomly
      divided into nine groups. Control group (Group-I) received distilled water
      interperitoneally for 7 days. Positive control group (Group-II) received 500
      mg/kg acetaminophen interperitoneally for 7 days. Commercially available seven
      symbiotic combinations at a dose of 10(9)cells/day for 3 weeks was administered
      to the tested groups (Group III-IX) after receiving 500 mg/kg/day acetaminophen
      interperitoneally for 7 days. Blood, kidney, liver and stool samples were
      collected after scarification for biochemical tests and DNA fragmentation assay
      of kidney tissue, kidney histological studies. Limited fecal analysis was
      conducted. RESULT: Blood urea nitrogen and toxicity indicators were increased,
      and antioxidant enzymes were decreased in Group-II. Blood urea nitrogen, toxicity
      indicators, glomerular necrosis, DNA damage of kidney tissue were reduced, and
      antioxidant enzymes were increased significantly in the treated Groups IV and IX
      (p < 0.05) in response to Group-II. Number of pathogenic bacteria decreased in
      synbiotic treated groups than Group I and II. CONCLUSION: The study demonstrated
      that some of commercial symbiotic combination can reduce the sever effect of
      kidney disease.

PMID- 24740593
TI  - Correlation between post over preoperative surrogate insulin resistance indexes'
      ratios and reversal of metabolic syndrome after Roux-en-Y gastric bypass.
AB  - Metabolic syndrome (MetS) is strongly linked to insulin resistance and has a high
      resolution rate after bariatric surgery. This study aims to determine whether
      post over preoperative ratios of surrogate insulin resistance markers (HOMA, TyG,
      and TG/HDL-c) are associated to postsurgical MetS reversal. This is a
      retrospective cohort study which involved 96 subjects with MetS who underwent
      Roux-en-Y gastric bypass (RYGB). Post over preoperative ratios of TyG and TG/HDL
      c indexes were statistically associated to MetS resolution. The use of these
      ratios as a way to assess postsurgical insulin sensitivity response appears to be
      a simple and useful tool in clinical practice. 

PMID- 24740594
TI  - Endoscopic treatment of gastric band prolapse.
AB  - Complications of laparoscopic adjustable gastric banding (LAGB) are well
      documented including migration, erosion, prolapse, infection, pouch dilatation,
      and gastric perforation. Band prolapse within the first 5 years after LAGB is
      observed in about 5% of cases, requiring an operative procedure. Here we report
      our experience of endoscopic treatment of band prolapses. From December 2007 to
      December 2013, 1,347 consecutive patients (202 male, 1,145 female) underwent
      LAGB; 47 patients had band prolapses and 7 were treated by endoscopy. All
      patients were women (median age, 34 years). The mean preoperative body mass index
      was 38.3 +/- 2.9 kg/m2. The mean duration to band prolapse after LAGB was 10.6 +/
      5.6 months. The mean duration of endoscopy was 12 +/- 3 min. One patient had
      recurrence of the prolapse 3 months after the first endoscopy and was treated by
      endoscopy again. There was no operative procedure required and no mortality.
      Endoscopic treatment of band prolapses is effective without the need for an
      operative procedure.

PMID- 24740595
TI  - Dietary iodine absorption is not influenced by malabsorptive bariatric surgery.
AB  - BACKGROUND: Bariatric surgery is accompanied by malabsorption of protein,
      carbohydrates, fats, vitamins, and trace elements. Iodine is essential to the
      synthesis of thyroid hormones. The aim of this study was to estimate the daily
      iodine intake in severely obese patients before and after bariatric surgery.
      METHODS: Thirty-five severely obese patients (obese group) with a BMI of 51.3 +/-
      8.3 kg/m(2) were studied before, 3 months, and 6 months after bariatric surgery.
      Eleven out of 35 patients were subjected to gastric bypass operation Roux-en-Y
      and 24 were subjected to a variant of biliopancreatic diversion with long limb
      procedure. The patients did not use any iodine supplements and no iodine
      antiseptics were administered during the operation. The messmates of the
      patients, following a similar diet (control group) with a BMI of 31.2 +/- 10.7
      kg/m(2), were also studied. Serum T3, T4, TSH, thyroid peroxidase antibodies,
      urinary iodine excretion (UIE) in a spot urine, and thyroid volume were measured
      in all subjects, at baseline and at 3- and 6-month follow-up in the obese group.
      RESULTS: UIE at baseline was similar in obese and control group (median (min
      max), 129.5 (24.9-462) vs. 138.9 (30.8-381) MUg/L, ns). In the obese group, a
      transient increase of UIE was observed 3 months after the operation and returned
      to baseline levels 6-months postsurgery. CONCLUSIONS: The UIE is not reduced
      after malabsorptive bariatric surgery, although all stomach, duodenum, and a
      substantial part of jejunum were bypassed. It appears that iodine is absorbed
      sufficiently along the remaining gastrointestinal tract.

PMID- 24740596
TI  - Efficacy, immunogenicity and safety of the HPV-16/18 AS04-adjuvanted vaccine in
      healthy Chinese women aged 18-25 years: results from a randomized controlled
      trial.
AB  - This phase II/III, double-blind, randomized trial assessed the efficacy,
      immunogenicity and safety of the human papillomavirus (HPV)-16/18 AS04-adjuvanted
      vaccine in young Chinese women (ClinicalTrials.gov registration NCT00779766).
      Women aged 18-25 years from Jiangsu province were randomized (1:1) to receive HPV
      vaccine (n = 3,026) or Al(OH)3 control (n = 3,025) at months 0, 1 and 6. The
      primary objective was vaccine efficacy (VE) against HPV-16/18 associated 6-month
      persistent infection (PI) and/or cervical intraepithelial neoplasia (CIN) 1+.
      Secondary objectives were VE against virological and clinical endpoints
      associated with HPV-16/18 and with high-risk HPV types, immunogenicity and
      safety. Mean follow-up for the according-to-protocol cohort for efficacy (ATP-E)
      was ~15 months after the third dose. In the ATP-E (vaccine = 2,889; control =
      2,894), for initially HPV DNA negative and seronegative subjects, HPV-16/18
      related VE (95% CI) was 94.2% (62.7, 99.9) against 6-month PI and/or CIN1+ and
      93.8% (60.2, 99.9) against cytological abnormalities. VE against HPV-16/18
      associated CIN1+ and CIN2+ was 100% (-50.4, 100) and 100% (-140.2, 100),
      respectively (no cases in the vaccine group and 4 CIN1+ and 3 CIN2+ cases in the
      control group). At Month 7, at least 99.7% of initially seronegative vaccine
      recipients had seroconverted for HPV-16/18; geometric mean antibody titres (95%
      CI) were 6,996 (6,212 to 7,880) EU/mL for anti-HPV-16 and 3,309 (2,942 to 3,723)
      EU/mL for anti-HPV-18. Safety outcomes between groups were generally similar. The
      HPV-16/18 AS04-adjuvanted vaccine is effective, immunogenic and has a clinically
      acceptable safety profile in young Chinese women. Prophylactic HPV vaccination
      has the potential to substantially reduce the burden of cervical cancer in China.

PMID- 24740597
TI  - Regulation of the proliferation and differentiation of Leydig stem cells in the
      adult testis.
AB  - We reported previously that stem cells associated with adult rat testis
      seminiferous tubules are able to give rise to differentiated Leydig cells in
      vitro. The regulatory mechanisms by which they do so, however, are uncertain.
      Herein, we hypothesized that the proliferation and differentiation of Leydig cell
      stem cells (stem Leydig cells, SLCs) depend upon locally produced factors from
      the seminiferous tubules. Microarray analysis revealed that platelet-derived
      growth factor receptor alpha (PDGFRalpha) is up-regulated and PDGFRbeta is down
      regulated with postnatal differentiation of SLCs. This suggested that their
      ligands, PDGF-AA and PDGF-BB, respectively, might have important roles in SLC
      proliferation and differentiation. To test this, we developed a unique in vitro
      culture system in which SLCs proliferate on the surfaces of cultured seminiferous
      tubules largely during Week 1 of culture and their progeny subsequently
      differentiate to testosterone-forming Leydig cells during Weeks 2 through 4.
      Using this system, seminiferous tubules from adult rat testes were cultured with
      PDGF-AA or PDGF-BB for up to 4 wk. Both ligands stimulated SLC proliferation
      during the first week of culture, with PDGF-BB significantly more potent than
      PDGF-AA. Furthermore, PDGF-AA had a stimulatory effect on SLC differentiation
      from Weeks 2 through 4 of culture. In contrast, PDGF-BB, which stimulated cell
      proliferation during Week 1, had a significant inhibitory effect on
      differentiation during Weeks 2 through 4. These findings, made possible by the
      development of the seminiferous tubule culture system, reveal distinct roles by
      locally produced PDGFs in SLC regulation. 

PMID- 24740598
TI  - Live cell imaging of in vitro human trophoblast syncytialization.
AB  - Human trophoblast syncytialization, a process of cell-cell fusion, is one of the
      most important yet least understood events during placental development.
      Investigating the fusion process in a placenta in vivo is very challenging given
      the complexity of this process. Application of primary cultured cytotrophoblast
      cells isolated from term placentas and BeWo cells derived from human
      choriocarcinoma formulates a biphasic strategy to achieve the mechanism of
      trophoblast cell fusion, as the former can spontaneously fuse to form the
      multinucleated syncytium and the latter is capable of fusing under the treatment
      of forskolin (FSK). Live-cell imaging is a powerful tool that is widely used to
      investigate many physiological or pathological processes in various animal models
      or humans; however, to our knowledge, the mechanism of trophoblast cell fusion
      has not been reported using a live- cell imaging manner. In this study, a live
      cell imaging system was used to delineate the fusion process of primary term
      cytotrophoblast cells and BeWo cells. By using live staining with Hoechst 33342
      or cytoplasmic dyes or by stably transfecting enhanced green fluorescent protein
      (EGFP) and DsRed2-Nuc reporter plasmids, we observed finger-like protrusions on
      the cell membranes of fusion partners before fusion and the exchange of
      cytoplasmic contents during fusion. In summary, this study provides the first
      video recording of the process of trophoblast syncytialization. Furthermore, the
      various live-cell imaging systems used in this study will help to yield molecular
      insights into the syncytialization process during placental development. 

PMID- 24740599
TI  - Immunohistological study of the endometrial stromal fibroblasts in the opossum,
      Monodelphis domestica: evidence for homology with eutherian stromal fibroblasts.
AB  - Molecular phylogenetic studies suggest that the hemochorial placentation and
      decidualization are ancestral traits of eutherian mammals. While the origin of
      the placental tissue is well understood, the origin of the decidual cells is
      unclear. Here we address the origin of decidual cells by examining the expression
      patterns of six transcription factors (TFs) as well as four structural proteins
      in the endometrium of a marsupial, Monodelphis domestica, and compared them with
      the patterns known from eutherian species. We found a mesenchymal cell population
      in the subepithelial compartment of the opossum endometrium. These cells express
      a set of TFs, such as homeobox A11 (HOXA11), CCAAT/enhancer-binding protein beta
      (CEBPB), and progesterone receptor (PGR), that are important for eutherian
      endometrial stromal cells. On the other hand, we did not find the expression of a
      decidual cell marker desmin (DES) or of TFs that are important for decidual cell
      differentiation, such as forkhead box O1 (FOXO1), in those cells. Based on these
      results, we propose that opossum has cells homologous to eutherian endometrial
      fibroblasts but no decidual cells. In addition, we describe cellular changes
      associated with the progression of pregnancy: nuclear localization of CEBPB in
      luminal epithelial cells as early as 8 days postcoitum, expansion of endometrial
      glands, nuclear localization of FOXO1 in glandular epithelial cells, and
      expression of smooth muscle actin in luminal epithelial cells. These data show
      that the luminal and glandular epithelium react to the presence of the
      preplacentation conceptus and suggest a limited form of pregnancy recognition. 

PMID- 24740600
TI  - Reduced endogenous estrogen and hemicastration interact synergistically to
      increase porcine sertoli cell proliferation.
AB  - Both reduced endogenous estrogen and hemicastration stimulate proliferation of
      porcine Sertoli cells. The objective of these experiments was to compare the
      temporal patterns of response to each stimulus with the response to the combined
      stimuli as indications of shared or separate mechanisms. Within a replicate, one
      littermate was treated weekly with canola oil vehicle and remained intact; a
      second littermate was treated weekly with vehicle, and one testis was removed at
      Day 8; a third littermate was treated weekly with the aromatase inhibitor
      letrozole to reduce endogenous estrogens and remained intact; and the fourth
      littermate was treated weekly with letrozole, and one testis was removed at Day
      8. Four replicates were evaluated at 2 wk of age, five replicates evaluated at
      6.5 wk of age, and five replicates were evaluated at 11 wk of age, with treatment
      ceasing at 6 wk of age. Numbers of Sertoli cells were determined following GATA4
      labeling using the optical dissector method. Levels of estradiol, estrogen
      conjugates, follicle-stimulating hormone (FSH), luteinizing hormone (LH), and
      inhibin were determined by radioimmunoassay. Hemicastration appeared to have a
      rapid effect on Sertoli cell proliferation, but letrozole treatment had no
      apparent effect on Sertoli cell numbers at 2 wk of age. Both letrozole treatment
      and hemicastration had stimulated Sertoli cell proliferation by 6.5 wk of age,
      although the magnitude of the hemicastration response was much greater. Letrozole
      appeared to have minimal interaction with hemicastration at this age. Letrozole
      and hemicastration together increased Sertoli cell numbers at 11 wk of age
      compared with either treatment alone. Estradiol and estrogen conjugates were
      dramatically reduced by aromatase inhibition as anticipated; treatment-induced
      changes in inhibin, LH, or FSH were minimal. Differences in timing of response
      and positive interaction at 11 wk of age suggest that hemicastration and
      letrozole stimulate proliferation of Sertoli cells by two initially different
      pathways. 

PMID- 24740601
TI  - Adenine nucleotide metabolism and a role for AMP in modulating flagellar
      waveforms in mouse sperm.
AB  - While most ATP, the main energy source driving sperm motility, is derived from
      glycolysis and oxidative phosphorylation, the metabolic demands of the cell
      require the efficient use of power stored in high-energy phosphate bonds. In
      times of high energy consumption, adenylate kinase (AK) scavenges one ATP
      molecule by transphosphorylation of two molecules of ADP, simultaneously yielding
      one molecule of AMP as a by-product. Either ATP or ADP supported motility of
      detergent-modeled cauda epididymal mouse sperm, indicating that flagellar AKs are
      functional. However, the ensuing flagellar waveforms fueled by ATP or ADP were
      qualitatively different. Motility driven by ATP was rapid but restricted to the
      distal region of the sperm tail, whereas ADP produced slower and more fluid waves
      that propagated down the full flagellum. Characterization of wave patterns by
      tracing and superimposing the images of the flagella, quantifying the differences
      using digital image analysis, and computer-assisted sperm analysis revealed
      differences in the amplitude, periodicity, and propagation of the waves between
      detergent-modeled sperm treated with either ATP or ADP. Surprisingly, addition of
      AMP to the incubation medium containing ATP recapitulated the pattern of sperm
      motility seen with ADP alone. In addition to AK1 and AK2, which we previously
      demonstrated are present in outer dense fibers and mitochondrial sheath of the
      mouse sperm tail, we show that another AK, AK8, is present in a third flagellar
      compartment, the axoneme. These results extend the known regulators of sperm
      motility to include AMP, which may be operating through an AMP-activated protein
      kinase. 

PMID- 24740602
TI  - Treatment with bazedoxifene and conjugated estrogens results in regression of
      endometriosis in a murine model.
AB  - Bazedoxifene (BZA), a selective estrogen receptor modulator (SERM), inhibits the
      action of estrogens on endometrial proliferation. Here, we evaluate the effect of
      a tissue-selective estrogen complex (TSEC) containing BZA and conjugated
      estrogens (CE) on ectopic endometrial lesions in a mouse model of endometriosis.
      Experimental endometriosis was created in 60 female CD-1 mice. The mice were
      randomly divided into 10 groups that received varying doses of either BZA (1, 2,
      3, or 5 mg/kg/day), BZA (1, 2, 3, or 5 mg/kg/day) in combination with CE (3
      mg/kg/day), CE treatment alone (3 mg/kg/day), or vehicle control for 8 wk.
      Treatment with BZA alone or the TSEC containing BZA/CE led to a decrease in
      endometriotic lesion size compared to controls. The mean surface area of the
      untreated lesions was 19.6 mm(2). Treatment with BZA or BZA/CE resulted in
      reduced lesion size (to 8.8 and 7.8 mm(2), respectively). No significant
      difference was found in lesion size between the BZA and BZA/CE treatment groups
      or between different doses of either treatment. Ovarian cyst formation was not
      evident in the treated groups. Treatment with the TSEC containing higher BZA
      dosages (3 and 5 mg/kg/day) led to significantly lower levels of estrogen
      receptor (Esr1) mRNA expression compared to the control treatment. No differences
      were observed in expression of progesterone receptor (Pgr). Immunohistochemical
      analysis also demonstrated a decrease in ESR protein. The combination of CE and
      BZA may prove to be a novel treatment option for endometriosis. 

PMID- 24740603
TI  - High-resolution profiling of novel transcribed regions during rat
      spermatogenesis.
AB  - Mammalian spermatogenesis is a complex and highly orchestrated combination of
      processes in which male germline proliferation and differentiation result in the
      production of mature spermatozoa. If recent genome-wide studies have contributed
      to the in-depth analysis of the male germline protein-encoding transcriptome,
      little effort has yet been devoted to the systematic identification of novel
      unannotated transcribed regions expressed during mammalian spermatogenesis. We
      report high-resolution expression profiling of male germ cells in rat, using next
      generation sequencing technology and highly enriched testicular cell populations.
      Among 20 424 high-confidence transcripts reconstructed, we defined a stringent
      set of 1419 long multi-exonic unannotated transcripts expressed in the testis
      (testis-expressed unannotated transcripts [TUTs]). TUTs were divided into 7
      groups with different expression patterns. Most TUTs share many of the
      characteristics of vertebrate long noncoding RNAs (lncRNAs). We also markedly
      reinforced the finding that TUTs and known lncRNAs accumulate during the meiotic
      and postmeiotic stages of spermatogenesis in mammals and that X-linked meiotic
      TUTs do not escape the silencing effects of meiotic sex chromosome inactivation.
      Importantly, we discovered that TUTs and known lncRNAs with a peak expression
      during meiosis define a distinct class of noncoding transcripts that exhibit
      exons twice as long as those of other transcripts. Our study provides new
      insights in transcriptional profiling of the male germline and represents a high
      quality resource for novel loci expressed during spermatogenesis that
      significantly contributes to rat genome annotation. 

PMID- 24740604
TI  - In vitro exposure of Leydig cells to an environmentally relevant mixture of
      organochlorines represses early steps of steroidogenesis.
AB  - Leydig cell steroidogenesis is mainly regulated by LH via increased cAMP
      production leading to STAR protein activation. STAR is essential for cholesterol
      shuttling inside mitochondria where steroidogenesis is initiated. Accumulating
      evidence suggest that persistent organochlorine compounds disrupt testicular
      function, but the mechanism of action remains poorly characterized. Here we
      report that in vitro exposure of MA-10 and MLTC-1 Leydig cells to an
      environmentally relevant mixture of 15 organochlorines impairs steroidogenesis.
      While having no effect on cell viability and basal steroid production, the
      organochlorine mixture caused a 50% decrease in cAMP-induced progesterone
      production. The mixture also reduced cAMP-induced 30 kDa STAR protein by 50%
      while having no effect on basal STAR protein. Basal or cAMP-induced Star mRNA
      levels and promoter activity were unaffected by the mixture, indicating that the
      organochlorine mixture acted at the translational/posttranslational level.
      Further supporting this is the fact that in COS-7 cells overexpressing STAR, the
      organochlorine mixture caused a decrease in the 30 kDa form of STAR and an
      accumulation of the 37 kDa forms. In addition to STAR, we found that the
      organochlorine mixture also decreases the levels of CYP11A1 and ADXR, two
      proteins essential for the conversion of cholesterol into pregnenolone. In
      conclusion, our data show that organochlorine exposure disrupts Leydig cell
      function by targeting different components of the steroidogenic pathway. 

PMID- 24740605
TI  - Multiple pathways mediate luteinizing hormone regulation of cGMP signaling in the
      mouse ovarian follicle.
AB  - Luteinizing hormone (LH) regulation of the epidermal growth factor (EGF) network
      is critical for oocyte maturation and the ovulatory process. Recent studies have
      indicated that C-type natriuretic peptide (CNP) and its receptor natriuretic
      peptide receptor B (NPR2) play an important role in the control of meiotic
      arrest. Here, we investigated the involvement of the EGF network in the LH
      dependent regulation of the CNP/NPR2 axis and cGMP accumulation. LH/hCG treatment
      causes a major decrease in both cGMP and the CNP precursor (natriuretic peptide
      precursor C [Nppc]) mRNA accumulation in vivo and in vitro. However, the cGMP
      downregulation precedes the decrease in Nppc mRNA by more than 1 h. Amphiregulin,
      an EGF-like factor, suppresses Nppc mRNA levels in cultured follicles to the same
      extent as LH, and this effect is completely prevented by the EGF receptor (EGFR)
      kinase inhibitor AG1478. However, the LH-dependent suppression of Nppc is
      insensitive to AG1478. Similarly, Nppc suppression by LH occurs in follicles from
      EGFR null mice. These findings document that EGFR signaling is sufficient to
      downregulate CNP, but is not necessary for LH action. When cGMP concentration in
      the follicle is measured, the short-term, but not long-term, LH effects on cGMP
      are prevented by AG1478, suggesting that ligand availability may be responsible
      for the late response. Human CG decreases the CNP-dependent cGMP synthesis in
      wild-type and EGFR knockdown cumulus-oocyte complexes. These findings demonstrate
      that redundant pathways are involved in the regulation of cGMP. EGFR-dependent
      events are involved in the short-term regulation of cGMP, whereas the long-term
      effects may involve regulation of the CNP. 

PMID- 24740607
TI  - Uterine epithelial cell changes during pregnancy in a marsupial (Sminthopsis
      crassicaudata; Dasyuridae).
AB  - Formation of a placenta requires intimate contact between the embryonic and
      maternal uterine epithelia in early pregnancy. Contact is accompanied by a
      characteristic suite of changes to the plasma membranes of uterine epithelial
      cells, termed the plasma membrane transformation. The plasma membrane
      transformation occurs in eutherian mammals and in viviparous (live-bearing)
      squamate reptiles, and may be fundamental to the evolution of viviparity in
      amniotes. Marsupials provide an excellent opportunity to test the generality of
      this phenomenon. Here, we present the first detailed study of the plasma membrane
      transformation in a marsupial. We combine electron microscopy and
      immunohistochemistry to describe morphological and molecular features of uterine
      epithelial cells during pregnancy in the fat-tailed dunnart (Sminthopsis
      crassicaudata; Dasyuridae). Cell morphology changes dramatically in S.
      crassicaudata during pregnancy. Apical microvilli are replaced by irregular blunt
      projections, then by spiky projections postimplantation. Cell surfaces flatten
      and ciliated cells are lost. Junctional complexes between adjacent cells increase
      in depth, then decrease just before implantation, which is consistent with
      junctional protein localization in this region of the cell membrane. The uterine
      cellular changes in S. crassicaudata are consistent with a plasma membrane
      transformation, and support the idea that this phenomenon is fundamental to the
      evolution of viviparity in amniote vertebrates.

PMID- 24740606
TI  - Validity of maternal and infant outcomes within nationwide Medicaid data.
AB  - PURPOSE: The aim of this study is to assess the validity of preeclampsia,
      congenital cardiac malformations, and persistent pulmonary hypertension of the
      newborn (PPHN) diagnoses in the US Medicaid Analytic eXtract (MAX), a nationwide
      health care utilization database that may be useful for perinatal research.
      METHODS: Using the 2000-2007 MAX, we identified more than 1 million pregnancies
      ending in live birth. We identified potential cases based on claims, reviewed
      their hospital medical records, and calculated the positive predictive values
      (PPVs) and 95% confidence intervals (CIs) using records as the reference.
      RESULTS: Among 183 women with any preeclampsia diagnoses, the PPV was 66.5%
      (53.6, 77.4%), but it increased to 94.5% (84.0, 98.3%) for inpatient preeclampsia
      diagnoses. The PPV for inpatient PPHN diagnoses (N = 82) was 68.3% (57.6, 77.4%),
      but it increased to 89.6% (CI: 77.8, 95.5%) when restricting to infants not
      transferred to another facility shortly after birth (N = 48). The PPV for cardiac
      malformations was 77.6% (65.7, 86.2%) when requiring inpatient codes on more than
      one date (N = 63). CONCLUSIONS: These PPVs are conservative, particularly when
      patients were transferred or received outpatient diagnoses, because we reviewed
      records from a single hospitalization only. PPVs improve with stringent
      identification criteria, at the cost of sensitivity, and can be used to correct
      for measurement error.

PMID- 24740608
TI  - Sequential pH-dependent adsorption of ionic amphiphilic diblock copolymer
      micelles and choline oxidase onto conductive substrates: toward the design of
      biosensors.
AB  - This work examines the fabrication regime and the properties of polymer-enzyme
      thin-films adsorbed onto conductive substrates (graphite or gold). The films are
      formed via two-steps, sequential adsorption of poly(n-butylmethacrylate)-block
      poly(N,N-dimethylaminoethyl methacrylate) (PnBMA-b-PDMAEMA) diblock copolymer
      micelles (1st step of adsorption), followed by the enzyme choline oxidase (ChO)
      (2nd step of adsorption). The solution properties of both adsorbed components are
      studied and the pH-dependent step-by-step fabrication of polymer-enzyme biosensor
      coatings reveals rather drastic differences in their enzymatic activities in
      dependence on the pH of both adsorption steps. The resulting hybrid thin-films
      represent highly active biosensors for choline with a low detection limit of 30
      nM and a good linearity in a range between 30 nM and 100 MUM. The sensitivity is
      found to be 175 MUA mM(-1) cm(-2) and the operational stability of the polymer
      enzyme thin-films can be additionally improved via enzyme-to-enzyme crosslinking
      with glutaraldehyde. 

PMID- 24740610
TI  - Mixed-valence ruthenium complexes rotating through a conformational Robin-Day
      continuum.
AB  - The conformational energy landscape and the associated electronic structure and
      spectroscopic properties (UV/Vis/near-infrared (NIR) and IR) of three formally
      d(5)/d(6) mixed-valence diruthenium complex cations, [{Ru(dppe)Cp*}2(MU
      C=CC6H4C=C)](+), [1](+), [trans-{RuCl(dppe)2}2(MU-C=CC6H4C=C)](+), [2](+), and
      the Creutz-Taube ion, [{Ru(NH3)5}2(MU-pz)](5+), [3](5+) (Cp = cyclopentadienyl;
      dppe = 1,2-bis(diphenylphosphino)ethane; pz = pyrazine), have been studied using
      a nonstandard hybrid density functional BLYP35 with 35 % exact exchange and
      continuum solvent models. For the closely related monocations [1](+) and [2](+),
      the calculations indicated that the lowest-energy conformers exhibited
      delocalized electronic structures (or class III mixed-valence character).
      However, these minima alone explained neither the presence of shoulder(s) in the
      NIR absorption envelope nor the presence of features in the observed vibrational
      spectra characteristic of both delocalized and valence-trapped electronic
      structures. A series of computational models have been used to demonstrate that
      the mutual conformation of the metal fragments--and even more importantly the
      orientation of the bridging ligand relative to those metal centers--influences
      the electronic coupling sufficiently to afford valence-trapped conformations,
      which are of sufficiently low energy to be thermally populated. Areas in the
      conformational phase space with variable degrees of symmetry breaking of
      structures and spin-density distributions are shown to be responsible for the
      characteristic spectroscopic features of these two complexes. The Creutz-Taube
      ion [3](5+) also exhibits low-lying valence-trapped conformational areas, but the
      electronic transitions that characterize these conformations with valence
      localized electronic structures have low intensities and do not influence the
      observed spectroscopic characteristics to any notable extent.

PMID- 24740609
TI  - Synaptotagmin II and gangliosides bind independently with botulinum neurotoxin B
      but each restrains the other.
AB  - Botulinum neurotoxin type B (BoNT/B) initiates its toxicity by binding to
      synaptotagmin II (SytII) and gangliosides GD1a and GT1b on the neural membrane.
      We synthesized two 27-residue peptides that carry the BoNT/B binding sites on
      mouse SytII (mSytII 37-63) or human SytII (hSytII 34-60). BoNT/B bound to these
      peptides, but showed substantially higher binding to mSytII peptide than to
      hSytII peptide. The mSytII peptide inhibited almost completely BoNT/B binding to
      synaptosomes (snps) and displayed a high affinity. BoNT/B bound strongly to
      mSytII peptide and binding was inhibited by the peptide. Binding of BoNT/B to
      snps was also inhibited (~80 %) by a larger excess of gangliosides GD1a or GT1b.
      The mSytII peptide inhibited very strongly (at least 80 %) the toxin binding to
      snps, while the two gangliosides were much less efficient inhibitors requiring
      much larger excess to achieve similar inhibition levels. Furthermore,
      gangliosides GD1a or GT1b inhibited BoNT/B binding to mSytII peptide at a much
      larger excess than the inhibition by mSytII peptide. Conversely, BoNT/B bound
      well to each ganglioside and binding could be inhibited by the correlate
      ganglioside and much less efficiently by the mSytII peptide. There was no
      apparent collaboration between mSytII peptide and either ganglioside. mSytII
      peptide displayed some protective activity in vivo in mice against a lethal
      BoNT/B dose. We concluded that SytII peptide and gangliosides bind independently
      but, with their binding sites on BoNT/B being spatially close, each can influence
      BoNT/B binding to the other due to regional conformational perturbations or
      steric interference or both. Ganglioside involvement in BoNT/B binding might help
      in toxin translocation and endocytosis.

PMID- 24740611
TI  - Straightforward 3D hydrodynamic focusing in femtosecond laser fabricated
      microfluidic channels.
AB  - We report on the use of femtosecond laser irradiation followed by chemical
      etching as a microfabrication tool for innovative microfluidic networks that
      implement hydrodynamic focusing. The capability of our microfabrication
      technology to interconnect microchannels in three dimensions was exploited to
      demonstrate 2D hydrodynamic focusing, either in the horizontal or in the vertical
      plane, and full 3D hydrodynamic focusing. In all cases only two inlets were
      required, one for the sample and one for the sheath flows. Fluidic
      characterization of all devices was provided. In addition, taking advantage of
      the possibility to write optical waveguides using the same technology, a
      monolithic cell counter based on 3D hydrodynamic focusing and integrated optical
      detection was validated. Counting rates up to 5000 cells s(-1) were achieved in
      this very compact device, where focusing and counting operations were implemented
      in less than 1 mm(3). Integration of this hydrodynamic focusing module into
      several devices fabricated by the same technology as optical cell stretchers and
      cell sorters is envisaged. 

PMID- 24740612
TI  - A particle based model to simulate microscale morphological changes of plant
      tissues during drying.
AB  - Fundamental understanding on microscopic physical changes of plant materials is
      vital to optimize product quality and processing techniques, particularly in food
      engineering. Although grid-based numerical modelling can assist in this regard,
      it becomes quite challenging to overcome the inherited complexities of these
      biological materials especially when such materials undergo critical processing
      conditions such as drying, where the cellular structure undergoes extreme
      deformations. In this context, a meshfree particle based model was developed
      which is fundamentally capable of handling extreme deformations of plant tissues
      during drying. The model is built by coupling a particle based meshfree
      technique: Smoothed Particle Hydrodynamics (SPH) and a Discrete Element Method
      (DEM). Plant cells were initiated as hexagons and aggregated to form a tissue
      which also accounts for the characteristics of the middle lamella. In each cell,
      SPH was used to model cell protoplasm and DEM was used to model the cell wall.
      Drying was incorporated by varying the moisture content, the turgor pressure, and
      cell wall contraction effects. Compared to the state of the art grid-based
      microscale plant tissue drying models, the proposed model can be used to simulate
      tissues under excessive moisture content reductions incorporating cell wall
      wrinkling. Also, compared to the state of the art SPH-DEM tissue models, the
      proposed model better replicates real tissues and the cell-cell interactions used
      ensure efficient computations. Model predictions showed good agreement both
      qualitatively and quantitatively with experimental findings on dried plant
      tissues. The proposed modelling approach is fundamentally flexible to study
      different cellular structures for their microscale morphological changes at
      dehydration. 

PMID- 24740613
TI  - Ecosystem services in urban landscapes: practical applications and governance
      implications.
AB  - Urban landscapes are the everyday environment for the majority of the global
      population, and almost 80 % of the Europeans live in urban areas. The continuous
      growth in the number and size of urban areas along with an increasing demand on
      resources and energy poses great challenges for ensuring human welfare in cities
      while preventing an increasing loss of biodiversity. The understanding of how
      urban ecosystems function, provide goods and services for urban dwellers; and how
      they change and what allows and limits their performance can add to the
      understanding of ecosystem change and governance in general in an ever more human
      dominated world. This Special Issue aims at bridging the knowledge gap among
      urbanization, demand creation, and provisioning of ecosystem services in urban
      regions on the one hand and schemes of urban governance and planning on the
      other. 

PMID- 24740614
TI  - A quantitative review of urban ecosystem service assessments: concepts, models,
      and implementation.
AB  - Although a number of comprehensive reviews have examined global ecosystem
      services (ES), few have focused on studies that assess urban ecosystem services
      (UES). Given that more than half of the world's population lives in cities,
      understanding the dualism of the provision of and need for UES is of critical
      importance. Which UES are the focus of research, and what types of urban land use
      are examined? Are models or decision support systems used to assess the provision
      of UES? Are trade-offs considered? Do studies of UES engage stakeholders? To
      address these questions, we analyzed 217 papers derived from an ISI Web of
      Knowledge search using a set of standardized criteria. The results indicate that
      most UES studies have been undertaken in Europe, North America, and China, at
      city scale. Assessment methods involve bio-physical models, Geographical
      Information Systems, and valuation, but few study findings have been implemented
      as land use policy. 

PMID- 24740615
TI  - Opportunities for increasing resilience and sustainability of urban social
      ecological systems: insights from the URBES and the cities and biodiversity
      outlook projects.
AB  - Urban futures that are more resilient and sustainable require an integrated
      social-ecological system approach to urban policymaking, planning, management,
      and governance. In this article, we introduce the Urban Biodiversity and
      Ecosystem Services (URBES) and the Cities and Biodiversity Outlook (CBO) Projects
      as new social-ecological contributions to research and practice on emerging urban
      resilience and ecosystem services. We provide an overview of the projects and
      present global urbanization trends and their effects on ecosystems and
      biodiversity, as a context for new knowledge generated in the URBES case-study
      cities, including Berlin, New York, Rotterdam, Barcelona, and Stockholm. The
      cities represent contrasting urbanization trends and examples of emerging science
      policy linkages for improving urban landscapes for human health and well-being.
      In addition, we highlight 10 key messages of the global CBO assessment as a
      knowledge platform for urban leaders to incorporate state-of-the-art science on
      URBES into decision-making for sustainable and resilient urban development. 

PMID- 24740616
TI  - Reconnecting cities to the biosphere: stewardship of green infrastructure and
      urban ecosystem services.
AB  - Within-city green infrastructure can offer opportunities and new contexts for
      people to become stewards of ecosystem services. We analyze cities as social
      ecological systems, synthesize the literature, and provide examples from more
      than 15 years of research in the Stockholm urban region, Sweden. The social
      ecological approach spans from investigating ecosystem properties to the social
      frameworks and personal values that drive and shape human interactions with
      nature. Key findings demonstrate that urban ecosystem services are generated by
      social-ecological systems and that local stewards are critically important.
      However, land-use planning and management seldom account for their role in the
      generation of urban ecosystem services. While the small scale patchwork of land
      uses in cities stimulates intense interactions across borders much focus is still
      on individual patches. The results highlight the importance and complexity of
      stewardship of urban biodiversity and ecosystem services and of the planning and
      governance of urban green infrastructure. 

PMID- 24740617
TI  - Development of a concept for non-monetary assessment of urban ecosystem services
      at the site level.
AB  - Determining the performance of ecosystem services at the city or regional level
      cannot accurately take into account the fine differences between green or gray
      structures. The supply of regulating ecosystem services in, for instance, parks
      can differ as parks vary in their land cover composition. A comprehensive
      ecosystem service assessment approach also needs to reflect land use to consider
      the demands placed on ecosystem services, which are mostly neglected by current
      research yet important for urban planning. For instance, if a sealed surface is
      no longer used, it could be unsealed to improve ecosystem service supply. Because
      of these scientific shortcomings, this article argues for a conceptual framework
      for the non-monetary assessment of urban ecosystem services at the site scale.
      This paper introduces a standardized method for selecting representative sites
      and evaluating their supply of and demand on ecosystem services. The conceptual
      design is supplemented by examples of Salzburg, Austria. 

PMID- 24740618
TI  - Contribution of ecosystem services to air quality and climate change mitigation
      policies: the case of urban forests in Barcelona, Spain.
AB  - Mounting research highlights the contribution of ecosystem services provided by
      urban forests to quality of life in cities, yet these services are rarely
      explicitly considered in environmental policy targets. We quantify regulating
      services provided by urban forests and evaluate their contribution to comply with
      policy targets of air quality and climate change mitigation in the municipality
      of Barcelona, Spain. We apply the i-Tree Eco model to quantify in biophysical and
      monetary terms the ecosystem services "air purification," "global climate
      regulation," and the ecosystem disservice "air pollution" associated with
      biogenic emissions. Our results show that the contribution of urban forests
      regulating services to abate pollution is substantial in absolute terms, yet
      modest when compared to overall city levels of air pollution and GHG emissions.
      We conclude that in order to be effective, green infrastructure-based efforts to
      offset urban pollution at the municipal level have to be coordinated with
      territorial policies at broader spatial scales. 

PMID- 24740619
TI  - Structural diversity: a multi-dimensional approach to assess recreational
      services in urban parks.
AB  - Urban green spaces provide important recreational services for urban residents.
      In general, when park visitors enjoy "the green," they are in actuality
      appreciating a mix of biotic, abiotic, and man-made park infrastructure elements
      and qualities. We argue that these three dimensions of structural diversity have
      an influence on how people use and value urban parks. We present a
      straightforward approach for assessing urban parks that combines multi
      dimensional landscape mapping and questionnaire surveys. We discuss the method as
      well the results from its application to differently sized parks in Berlin and
      Salzburg. 

PMID- 24740620
TI  - From valuation to governance: using choice experiment to value street trees.
AB  - This paper reports a choice experiment used to estimate the value of street trees
      in the city center of Lodz, Poland, and the broader context of how valuation
      results helped to improve governance of urban ecosystem services in this city.
      Based on a simplified inventory of trees, we prepared a set of hypothetical
      programs which put varying emphasis on the different ways to increase the numbers
      of trees, along with different levels of a hypothetical tax that would have to be
      paid by respondents to implement a given program. Our study indicated that the
      351 surveyed Lodz residents were willing to pay the highest price for greening
      those streets where currently there are few or no trees and confirmed the general
      importance of planting trees. The results provided an argument in the debate on
      the new development strategy for the city and helped to promote the concept of
      ecosystem services. 

PMID- 24740621
TI  - Urban ecosystem services for resilience planning and management in New York City.
AB  - We review the current state of knowledge about urban ecosystem services in New
      York City (NYC) and how these services are regulated, planned for, and managed.
      Focusing on ecosystem services that have presented challenges in NYC-including
      stormwater quality enhancement and flood control, drinking water quality, food
      provisioning and recreation-we find that mismatches between the scale of
      production and scale of management occur where service provision is insufficient.
      Adequate production of locally produced services and services which are more
      accessible when produced locally is challenging in the context of dense urban
      development that is characteristic of NYC. Management approaches are needed to
      address scale mismatches in the production and consumption of ecosystem services.
      By coordinating along multiple scales of management and promoting best management
      practices, urban leaders have an opportunity to ensure that nature and ecosystem
      processes are protected in cities to support the delivery of fundamental urban
      ecosystem services. 

PMID- 24740622
TI  - From multifunctionality to multiple ecosystem services? A conceptual framework
      for multifunctionality in green infrastructure planning for urban areas.
AB  - Green infrastructure (GI) and ecosystem services (ES) are promoted as concepts
      that have potential to improve environmental planning in urban areas based on a
      more holistic understanding of the complex interrelations and dynamics of social
      ecological systems. However, the scientific discourses around both concepts still
      lack application-oriented frameworks that consider such a holistic perspective
      and are suitable to mainstream GI and ES in planning practice. This literature
      review explores how multifunctionality as one important principle of GI planning
      can be operationalized by approaches developed and tested in ES research.
      Specifically, approaches developed in ES research can help to assess the
      integrity of GI networks, balance ES supply and demand, and consider trade-offs.
      A conceptual framework for the assessment of multifunctionality from a social
      ecological perspective is proposed that can inform the design of planning
      processes and support stronger exchange between GI and ES research. 

PMID- 24740623
TI  - Assessment of soil sealing management responses, strategies, and targets toward
      ecologically sustainable urban land use management.
AB  - Soil sealing has negative impacts on ecosystem services since urban green and
      soil get lost. Although there is political commitment to stop further sealing, no
      reversal of this trend can be observed in Europe. This paper raises the questions
      (1) which strategies can be regarded as being efficient toward ecologically
      sustainable management of urban soil sealing and (2) who has competences and
      should take responsibility to steer soil sealing? The analyses are conducted in
      Germany. The assessment of strategies is carried out using indicators as part of
      a content analysis. Legal-planning, informal-planning, economic-fiscal, co
      operative, and informational strategies are analyzed. Results show that there is
      a sufficient basis of strategies to secure urban ecosystem services by protecting
      urban green and reducing urban gray where microclimate regulation is a main
      target. However, soil sealing management lacks a spatial strategically overview
      as well as the consideration of services provided by fertile soils. 

PMID- 24740624
TI  - The dynamics of urban ecosystem governance in Rotterdam, the Netherlands.
AB  - We explore whether Rotterdam city has the governance capacity in terms of
      processes at place, and the attention in terms of vision and strategy to take up
      an integrated approach toward urban resilience. We adopt an interpretative policy
      analysis approach to assess the dynamics of urban ecosystem governance
      considering interviews, gray literature, and facilitated dialogues with policy
      practitioners. We show the inner workings of local government across strategic,
      operational, tactical, and reflective governance processes about the way urban
      ecosystems are regulated. Despite the existing capacity to steer such processes,
      a number of underlying challenges exist: need for coordination between planning
      departments; need to ease the integration of new policy objectives into
      established adaptive policy cycles; and need to assess the lessons learnt from
      pilots and emerging green initiatives. Regulating and provisioning ecosystem
      services receive heightened policy attention. Focus on regulating services is
      maintained by a policy renewal cycle that limits and delays consideration of
      other ecosystem services in policy and planning. 

PMID- 24740625
TI  - DNA-templated assembly of a heterobivalent quantum dot nanoprobe for extra- and
      intracellular dual-targeting and imaging of live cancer cells.
AB  - Quantum dots (QDs) hold great promise for the molecular imaging of cancer because
      of their superior optical properties. Although cell-surface biomarkers can be
      readily imaged with QDs, non-invasive live-cell imaging of critical intracellular
      cancer markers with QDs is a great challenge because of the difficulties in the
      automatic delivery of QD probes to the cytosol and the ambiguity of intracellular
      targeting signals. Herein, we report a new type of DNA-templated heterobivalent
      QD nanoprobes with the ability to target and image two spatially isolated cancer
      markers (nucleolin and mRNA) present on the cell surface and in the cell cytosol.
      Bypassing endolysosomal sequestration, this type of QD nanoprobes undergo
      macropinocytosis following the nucleolin targeting and then translocate to the
      cytosol for mRNA targeting. Fluorescence resonance energy transfer (FRET) based
      confocal microscopy enables unambiguous signal deconvolution of mRNA-targeted QD
      nanoprobes inside cancer cells. 

PMID- 24740626
TI  - Malignant transformation of infantile hemangioma to angiosarcoma: response to
      chemotherapy with bevacizumab.
AB  - We describe a child initially diagnosed with multi-focal infantile hemangioma
      (cutaneous, hepatic, pulmonary), a benign vascular lesion, which underwent
      malignant transformation to angiosarcoma. The use of anti-angiogenic agents, such
      as bevacizumab, an anti-vascular endothelial growth factor (VEGF) antibody, has
      been reported in adults with angiosarcoma. Treatment with chemotherapy
      (gemcitabine and docetaxel) and bevacizumab resulted in disease response with
      progression free survival of 12 months. This report describes the response to
      chemotherapy and bevacizumab in a child with angiosarcoma and highlights the
      potential for malignant transformation of benign vascular lesions and the need
      for careful monitoring.

PMID- 24740627
TI  - Prolonged QT dispersion in the infants of diabetic mothers.
AB  - Myocardial hypertrophy and cardiac dysfunction frequently occur in newborns of
      diabetic mothers. The authors hypothesized that wall hypertrophy or
      disproportionate left ventricular wall thickness in newborns of diabetic mothers
      may affect both QT and QTc dispersion. This study aimed to assess whether left
      ventricular hypertrophy affects the QT variables of infants born to diabetic
      mothers. This prospective cross-sectional study was conducted with 47
      consecutively selected neonates of gestational diabetic mothers and 30 healthy
      neonates born to healthy mothers. All the subjects were evaluated during the
      neonatal period. Electrocardiography with echocardiography was performed for the
      patients and the control subjects. The newborns of the diabetic mothers were
      classified according to septal thickness as group 1 (16 newborns with septal
      hypertrophy) or group 2 (31 newborns without septal hypertrophy). The study group
      consisted of three cohorts: groups 1, 2, and 3 (control group). Both QT and QTc
      dispersion were computed from a randomly selected beat as well as from an average
      beat derived from 12 beats included in a 10-s electrocardiography. A total of 16
      infants (34%) had a septal thickness of 6 mm or greater. The left ventricular end
      systolic diameter in group 1 was smaller (p = 0.0029) than in groups 2 and 3 (p =
      0.003). The interventricular septal thickness at end diastole (IVSTd) and the
      left ventricular posterior wall thickness at end diastole in group 1 were higher
      than in of groups 2 and 3. The QT and QTc dispersion intervals were longer in
      group 1 than in groups 2 and 3 (p < 0.001), and a highly significant positive
      correlation was detected between IVSTd and QT dispersion (r = 0.514, p = 0.042).
      Elevated QT and QTc dispersions may be risk factors for the development of
      arrhythmias in newborns of diabetic mothers. These patients may critically need
      systematic cardiac screening.

PMID- 24740628
TI  - Maternal medication use, fetal 3435 C>T polymorphism of the ABCB1 gene, and risk
      of isolated septal defects in a Han Chinese population.
AB  - The fundamental etiology of the majority of nonsyndromic congenital heart defects
      is commonly believed to involve the interaction of multiple environmental and
      genetic factors. This study aimed to explore the joint effects of fetal 3435 C>T
      polymorphism in the ABCB1 gene and maternal medication use on the risk of septal
      defects in a Han Chinese population. An age- and gender-matched case-control
      study involving 265 pairs was conducted from March 2012 to September 2013.
      Information on maternal periconceptional medication use was obtained through
      questionnaires. The genotyping of 3435 C>T polymorphism was performed by
      sequencing. Logistic regression analysis was performed to assess the joint
      effects of ABCB1 gene 3435 C>T polymorphism and maternal medication use on the
      risk of septal defects. Use of maternal medication periconceptionally was
      significantly associated with an increased risk of septal defects [adjusted odds
      ratio (OR) 2.133; 95 % confidence interval (CI) 1.361-3.444; P = 0.001)]. The
      genotype distributions of 3435 C>T polymorphism differed significantly between
      cases and control subjects (P < 0.001). Meanwhile, more patients were carriers of
      the ABCB1 CC/CT genotypes, which were significantly associated with an increased
      risk of septal defects (OR 2.414; 95 % CI 1.418-4.110; P = 0.001). Children who
      carry the CC/CT genotype and have been exposed periconceptionally to medication
      have an almost fourfold increased risk of having septal defects than nonexposed
      children with the TT genotype (adjusted OR 3.932; 95 % CI 1.708-9.051),
      particularly perimembranous ventricular septal defects (VSD) (adjusted OR 4.070;
      95 % CI 1.570-10.552). In conclusion, fetal 3435 C>T polymorphism in the ABCB1
      gene increases the risk for isolated septal defects in the presence of maternal
      medication use periconceptionally, particularly for perimembranous VSD.

PMID- 24740629
TI  - Cocaine- and amphetamine-regulated transcript peptide (CARTp): distribution and
      function in rat urinary bladder.
AB  - We investigated the distribution of CARTp(55-102) in rat lower urinary tract and
      evaluated its effect on urinary bladder function in vitro. Immunohistochemistry
      and a vertical isolated tissue bath system were used. Neurons, clusters of
      nonneuronal endocrine cells, and nerve fibers stained positive for CARTp(55-102)
      in young adult rat urinary bladder. The CARTp-expressing neuronal elements were
      nitric oxide synthase (NOS)- and tyrosine hydroxylase (TH)-IR, whereas all
      nonneuronal CARTp-IR elements stained positively only for TH (100 %). In isolated
      bladder strips, CARTp significantly increased the amplitude of electric field
      stimulation (EFS)-induced detrusor contractions at stimulation frequencies <=12.5
      Hz (p <= 0.001) as well as amplitude and frequency of spontaneous phasic urinary
      bladder smooth muscle (UBSM) contractions (p <= 0.05). The responses to CARTp
      stimulation were dose-dependent and increased in the presence of the urothelium.
      To determine if the CARTp increase in nerve-mediated contractions may involve an
      action of CARTp on specific neural pathways, we blocked cholinergic, purinergic,
      and adrenergic pathways and determined CARTp actions on EFS-medicated
      contractions. CARTp enhancement of EFS-mediated contractions does not involve
      alteration in purinergic, adrenergic, or cholinergic pathways. The study
      demonstrates that CARTp(55-102) is highly expressed in rat urinary bladder. CARTp
      increased the amplitude of EFS-induced detrusor contractions as well as the
      amplitude and frequency of spontaneous phasic urinary bladder smooth muscle
      contractions. We conclude that CARTp may alter the release of compounds from the
      urothelium that leads to an enhancement of UBSM contractility/excitability. 

PMID- 24740630
TI  - Prevalence of human papillomavirus in adolescent girls before reported sexual
      debut.
AB  - BACKGROUND: Human papillomavirus (HPV) vaccines are recommended for girls prior
      to sexual debut because they are most effective if administered before girls
      acquire HPV. Little research has been done on HPV prevalence in girls who report
      not having passed sexual debut in high HPV-prevalence countries. METHODS: Using
      attendance registers of randomly selected primary schools in the Mwanza region of
      Tanzania, we enrolled girls aged 15-16 years who reported not having passed
      sexual debut. A face-to-face interview on sexual behavior and intravaginal
      practices, and a nurse-assisted self-administered vaginal swab were performed.
      Swabs were tested for 13 high-risk and 24 low-risk HPV genotypes. RESULTS: HPV
      was detected in 40/474 (8.4%; 95% confidence interval [CI], 5.9-11.0) girls. Ten
      different high-risk and 21 different low-risk genotypes were detected. High-risk
      genotypes were detected in 5.3% (95% CI, 3.5-7.8). In multivariable analysis,
      only intravaginal cleansing (practiced by 20.9%) was associated with HPV
      detection (adjusted odds ratio = 2.19, 95% CI, 1.09-4.39). CONCLUSION: This
      cohort of adolescent Tanzanian girls had a high HPV prevalence prior to self
      reported sexual debut, and this was associated with intravaginal cleansing. This
      most likely reflects underreporting of sexual activity, and it is possible that
      intravaginal cleansing is a marker for unreported sexual debut or nonpenetrative
      sexual behaviors.

PMID- 24740632
TI  - Prevalence of human papillomavirus infection in adolescent girls before reported
      sexual debut.

PMID- 24740631
TI  - Targeting Staphylococcus aureus alpha-toxin as a novel approach to reduce
      severity of recurrent skin and soft-tissue infections.
AB  - Staphyococcus aureus frequently causes recurrent skin and soft-tissue infection
      (SSTI). In the pediatric population, elevated serum antibody targeting S. aureus
      alpha-toxin is correlated with a reduced incidence of recurrent SSTI. Using a
      novel model of recurrent SSTI, we demonstrated that expression of alpha-toxin
      during primary infection increases the severity of recurrent disease. Antagonism
      of alpha-toxin by either a dominant-negative toxin mutant or a small molecule
      inhibitor of the toxin receptor ADAM10 during primary infection reduces
      reinfection abscess severity. Early neutralization of alpha-toxin activity during
      S. aureus SSTI therefore offers a new therapeutic strategy to mitigate primary
      and recurrent disease. 

PMID- 24740634
TI  - Outcomes of preoperative bridging therapy for patients undergoing surgery after
      coronary stent implantation: a weighted meta-analysis of 280 patients from eight
      studies.
AB  - BACKGROUND: Preoperative bridging with a glycoprotein IIb/IIIa inhibitor is often
      performed in patients with prior coronary stents undergoing surgery who require
      antiplatelet therapy discontinuation, but its safety and efficacy have received
      limited study. We performed a weighted meta-analysis of the outcomes in patients
      with coronary stents undergoing bridging with glycoprotein IIb/IIIa inhibitors
      prior to surgery. METHODS: We conducted a weighted meta-analysis of preoperative
      bridging studies published between 2002 and 2013 in patients with coronary stents
      undergoing surgery. Data on in-hospital mortality, stent thrombosis, bleeding,
      hemoglobin decrease, blood transfusion, time to hospital discharge and myocardial
      infarction were collected. RESULTS: A total of eight studies with 280 patients
      were included. Pooled estimates of outcomes were as follows: in-hospital
      mortality 3.5% (95% confidence interval [CI] 1.7-5.9%); stent thrombosis 1.3%
      (95% CI 0.3-3.0%); major bleeding 7.4% (95% CI 2.8-14.1%); any bleeding 20.6%
      (95% CI 4.8-43.2%); mean decrease in hemoglobin 2.8 g/dL (95% CI 2.5-3.0 g/dL);
      mean blood loss 271 mL (95% CI 211-311 mL); blood transfusion 13.9% (95% CI 1.0
      38.2%); time to hospital discharge 5.9 days (95% CI 4.4-7.3 days); and myocardial
      infarction 1.6% (95% CI 0.3-3.6%). CONCLUSIONS: Preoperative bridging with a
      glycoprotein IIb/IIIa inhibitor in patients undergoing surgery after coronary
      stenting does not abolish the risk of perioperative stent thrombosis and may
      carry increased risk for bleeding. (c) 2014 Wiley Periodicals, Inc.

PMID- 24740635
TI  - Synthesis and characterization of a mercury-containing trimetalloboride.
AB  - The reaction of phenylmercuric chloride with an anionic dimanganese borylene
      (Li(+)[Cp2(CO)4Mn2B](-)) led to the formation of a trimetalloboride featuring the
      first reported bond between mercury and a non-cluster boron atom. Examination by
      (199)Hg NMR indicated (11)B-(199)Hg scalar coupling. Theoretical calculations
      indicated the nature of bonding to be sigma-donation from a B-Mn pi-orbital to
      Hg, in conjunction with weak Hgd->pi* back-donation. 

PMID- 24740633
TI  - HIV-1 drug resistance in the iPrEx preexposure prophylaxis trial.
AB  - BACKGROUND: The iPrEx study demonstrated that combination oral emtricitabine and
      tenofovir disoproxil fumarate (FTC/TDF) as preexposure prophylaxis (PrEP)
      protects against HIV acquisition in men who have sex with men and transgender
      women. Selection for drug resistance could offset PrEP benefits. METHODS:
      Phenotypic and genotypic clinical resistance assays characterized major drug
      resistant mutations. Minor variants with FTC/TDF mutations K65R, K70E, M184V/I
      were measured using 454 deep sequencing and a novel allele-specific polymerase
      chain reaction (AS-PCR) diagnostic tolerant to sequence heterogeneity. RESULTS:
      Control of primer-binding site heterogeneity resulted in improved accuracy of
      minor variant measurements by AS-PCR. Of the 48 on-study infections randomized to
      FTC/TDF, none showed FTC/TDF mutations by clinical assays despite detectable drug
      levels in 8 participants. Two randomized to FTC/TDF had minor variant M184I
      detected at 0.53% by AS-PCR or 0.75% by deep sequencing, only 1 of which had low
      but detectable drug levels. Among those with acute infection at randomization to
      FTC/TDF, M184V or I mutations that were predominant at seroconversion waned to
      background levels within 24 weeks after discontinuing drug. CONCLUSIONS: Drug
      resistance was rare in iPrEx on-study FTC/TDF-randomized seroconverters, and only
      as low-frequency minor variants. FTC resistance among those initiating PrEP with
      acute infection waned rapidly after drug discontinuation. Clinical Trials
      Registration.NCT00458393.

PMID- 24740636
TI  - Cumulative effect of genome-wide association study-identified genetic variants
      for bladder cancer.
AB  - Recent genome-wide association studies have identified 14 genetic variants
      associated with bladder cancer in Caucasians. The effects of these risk variants
      and their cumulative effects in Asian populations are unknown. We genotyped these
      newly identified variants in a case-control study of 1,050 patients diagnosed
      with bladder cancer and 1,404 controls in the Chinese population. Odds rations
      (ORs) and 95% confidence intervals (CIs) were computed by logistic regression,
      and cumulative effect of risk alleles were evaluated. Overall, seven of the 14
      variants were significantly associated with bladder cancer risk (p = 9.763 * 10(
      3) for rs9642880 at 8q24.21, p = 3.004 * 10(-3) for rs2294008 at 8q24.3, p =
      0.012 for rs798766 at 4p16.3, p = 0.034 for rs1495741 at 8p22, p = 2.306 * 10(-4)
      for GSTM1, p = 8.507 * 10(-8) for rs17674580 at 18q12.3, p = 7.179 * 10(-4) for
      rs10936599 at 3q26.2) and the odds ratios (ORs) ranged from 1.13 to 1.65.
      Moreover, there were a significant increased risk for bladder cancer positively
      correlated numbers of risk alleles and smoking status (Ptrend  = 7.060 * 10(-16)
      ). However, no allelic interaction effects on bladder cancer risk were observed
      between cumulative effects of variants and clinical characteristics. These
      findings suggest that seven bladder cancer risk-associated variants (rs9642880,
      rs2294008, rs798766, rs1495741, GSTM1 null, rs17674580 and rs10936599) may be
      used, collectively, to effectively measure inherited risk for bladder cancer.

PMID- 24740638
TI  - Carbonic anhydrase mediated carbon dioxide sequestration: promises, challenges
      and future prospects.
AB  - Anthropogenic activities have substantially increased the level of greenhouse
      gases (GHGs) in the atmosphere and are contributing significantly to the global
      warming. Carbon dioxide (CO2 ) is one of the major GHGs which plays a key role in
      the climate change. Various approaches and methodologies are under investigation
      to address CO2 capture and sequestration worldwide. Carbonic anhydrase (CA)
      mediated CO2 sequestration is one of the promising options. Therefore, the
      present review elaborates recent developments in CA, its immobilization and
      bioreactor methodologies towards CO2 sequestration using the CA enzyme. The
      promises and challenges associated with the efficient utilization of CA for CO2
      sequestration and scale up from flask to lab-scale bioreactor are critically
      discussed. Finally, the current review also recommends the possible future needs
      and directions to utilize CA for CO2 sequestration. 

PMID- 24740637
TI  - Novel markers identify nervous system components of the holothurian nervous
      system.
AB  - Echinoderms occupy a key position in the evolution of deuterostomes. As such, the
      study of their nervous system can shed important information on the evolution of
      the vertebrate nervous system. However, the study of the echinoderm nervous
      system has lagged behind when compared to that of other invertebrates due to the
      lack of tools available. In this study, we tested three commercially available
      antibodies as markers of neural components in holothurians. Immunohistological
      experiments with antibodies made against the mammalian transcription factors Pax6
      and Nurr1, and against phosphorylated histone H3 showed that these markers
      identified cells and fibers within the nervous system of Holothuria glaberrima.
      Most of the fibers recognized by these antibodies were co-labeled with the well
      known neural marker, RN1. Additional experiments showed that similar
      immunoreactivity was found in the nervous tissue of three other holothurian
      species (Holothuria mexicana, Leptosynapta clarki and Sclerodactyla briareus),
      thus extending our findings to the three orders of Holothuroidea. Furthermore,
      these markers identified different subdivisions of the holothurian nervous
      system. Our study presents three additional markers of the holothurian nervous
      system, expanding the available toolkit to study the anatomy, physiology,
      development and evolution of the echinoderm nervous system.

PMID- 24740639
TI  - Asymptomatic and isolated accessory mitral valve tissue in an adult.
AB  - Accessory mitral valve (AMV) tissue is a congenital anomaly that occurs in
      association with other congenital anomalies, and is an uncommon cause of left
      ventricular outflow tract obstruction. It is usually detected in early childhood
      when accompanied by symptoms of obstruction of the left ventricular outflow
      tract, and is rarely diagnosed in adults. We present a case of a 53-year-old man
      who was referred to our institution for evaluation of a systolic heart murmur.
      Echocardiography disclosed a diagnosis of AMV tissue. This case was uncommon
      because of the lack of severe obstruction of left ventricular outflow, cardiac
      symptoms, or other cardiac anomalies. We were able to carry out surgical
      resection of AMV tissue to avert possible progression of aortic insufficiency and
      the risk of a cerebrovascular embolization. The patient's postoperative course
      was uneventful, and postoperative echocardiography showed no residual accessory
      mitral tissue. 

PMID- 24740640
TI  - Surgical treatment of nontuberculous mycobacterial lung disease.
AB  - While the prevalence of pulmonary tuberculosis has been decreasing, the
      prevalence of nontuberculous mycobacterial lung disease has been increasing.
      Unlike tuberculosis, nontuberculous mycobacterial disease is not communicable.
      However, their indolent nature may result in extensive parenchymal destruction,
      causing respiratory failure and vulnerability to airway infection. Nontuberculous
      mycobacterial lung disease, therefore, has been becoming a significant health
      problem. According to the 2007 American Thoracic Society/Infectious Diseases
      Society of America statement on nontuberculous mycobacterial diseases, the
      primary treatment is a multidrug treatment regimen. However, its efficacy is less
      than satisfactory for Mycobacterium avium complex lung disease, which is the most
      common type of nontuberculous mycobacterial lung diseases, and for Mycobacterium
      abscessus lung disease, which is notoriously resistant to chemotherapeutic drugs.
      The statement, therefore, has proposed a multidisciplinary treatment approach for
      these types of nontuberculous mycobacterial lung diseases: a combination of
      multidrug treatment regimen and adjuvant resectional surgery. This review covers
      the rationale, indication, procedure, and outcome of surgical treatment of
      nontuberculous mycobacterial lung disease. The rationale of surgery is to prevent
      disease progressing by removing the areas of lung most affected, harboring the
      largest amounts of mycobacteria. The indications for surgery include a poor
      response to drug therapy, the development of macrolide-resistant disease, or the
      presence of a significant disease-related complication such as hemoptysis. The
      surgical procedures of choice are various types of pulmonary resections,
      including wedge resection, segmentectomy, lobectomy, or pneumonectomy. The
      reported series have achieved favorable treatment outcomes in surgically treated
      patients with acceptable morbidity and mortality rates. 

PMID- 24740642
TI  - Health in post-Black Death London (1350-1538): age patterns of periosteal new
      bone formation in a post-epidemic population.
AB  - Previous research has shown that the Black Death targeted older adults and
      individuals who had been previously exposed to physiological stressors. This
      project investigates whether this selectivity of the Black Death, combined with
      post-epidemic rising standards of living, led to significant improvements in
      patterns of skeletal stress markers, and by inference in health, among survivors
      and their descendants. Patterns of periosteal lesions (which have been previously
      shown, using hazard analysis, to be associated with elevated risks of mortality
      in medieval London) are compared between samples from pre-Black Death (c. 1,000
      1,300, n = 464) and post-Black Death (c. 1,350-1,538, n = 133) London cemeteries.
      To avoid the assumptions that stress markers alone provide a direct measure of
      health and that a change in frequencies of the stress marker by itself indicates
      changes in health, this study assesses age-patterns of the stress marker to
      obtain a more nuanced understanding of the population-level effects of an
      epidemic disease. Age-at-death in these samples is estimated using transition
      analysis, which provides point estimates of age even for the oldest adults in
      these samples and thus allows for an examination of physiological stress across
      the lifespan. The frequency of lesions is significantly higher in the post-Black
      Death sample, which, at face value, might indicate a general decline in health.
      However, a significant positive association between age and periosteal lesions,
      as well as a significantly higher number of older adults in the post-Black Death
      sample more likely suggests improvements in health following the epidemic.

PMID- 24740641
TI  - Early detection of thrombin activity in neuroinflammatory disease.
AB  - Although multiple sclerosis (MS) has been associated with the coagulation system,
      the temporal and spatial regulation of coagulation activity in neuroinflammatory
      lesions is unknown. Using a novel molecular probe, we characterized the activity
      pattern of thrombin, the central protease of the coagulation cascade, in
      experimental autoimmune encephalomyelitis. Thrombin activity preceded onset of
      neurological signs, increased at disease peak, and correlated with fibrin
      deposition, microglial activation, demyelination, axonal damage, and clinical
      severity. Mice with a genetic deficit in prothrombin confirmed the specificity of
      the thrombin probe. Thrombin activity might be exploited for developing sensitive
      probes for preclinical detection and monitoring of neuroinflammation and MS
      progression.

PMID- 24740643
TI  - Enabling practical surface acoustic wave nebulizer drug delivery via amplitude
      modulation.
AB  - A practical, commercially viable microfluidic device relies upon the
      miniaturization and integration of all its components--including pumps,
      circuitry, and power supply--onto a chip-based platform. Surface acoustic waves
      (SAW) have become popular in microfluidic manipulation, in solving the problems
      of microfluidic manipulation, but practical applications employing SAW still
      require more power than available via a battery. Introducing amplitude modulation
      at 0.5-40 kHz in SAW nebulization, which requires the highest energy input levels
      of all known SAW microfluidic processes, halves the power required to 1.5 W even
      while including the power in the sidebands, suitable for small lithium ion
      batteries, and maintains the nebulization rate, size, and size distributions
      vital to drug inhalation therapeutics. This simple yet effective means to enable
      an integrated SAW microfluidics device for nebulization exploits the relatively
      slow hydrodynamics and is furthermore shown to deliver shear-sensitive
      biomolecules--plasmid DNA and antibodies as exemplars of future pulmonary gene
      and vaccination therapies--undamaged in the nebulized mist. Altogether, the
      approach demonstrates a means to offer truly micro-scale microfluidics devices in
      a handheld, battery powered SAW nebulization device.

PMID- 24740644
TI  - Magnetic nanoclusters engineered by polymer-controlled self-assembly for the
      accurate diagnosis of atherosclerotic plaques via magnetic resonance imaging.
AB  - Oleyl dextran-coated magnetic nanoclusters (ODMCs) are fabricated for the
      accurate detection of macrophage-rich atherosclerotic plaques using magnetic
      resonance (MR) imaging. Dextran is introduced to the cluster surface of magnetic
      nanocrystals (MNCs) through self-assembly using amphiphilic oleic acid-conjugated
      dextran (ODex) to provide not only hydrophilicity but also a high affinity to
      macrophages. Enhanced magnetism of the ODMCs is engineered by optimizing the
      degree of substitution (DS) of the oleyl group in ODex and the concentration of
      ODex used for the synthesis of ODMC. Consequently, ODMCs exhibit significantly
      increased T2 relaxivity and excellent macrophage-targeting ability without
      cytotoxicity, in vitro. Moreover, in vivo T2-weighted MR imaging after
      intravenous injection of ODMCs into a rat artery balloon injury model
      demonstrates considerable MR contrast strength efficacy in the plaques of the
      injured carotid artery. These novel ODMCs may offer a highly efficient MR imaging
      nanoprobes for the selective diagnosis of atherosclerosis. 

PMID- 24740645
TI  - FRETS-VWF73 rather than CBA assay reflects ADAMTS13 proteolytic activity in
      acquired thrombotic thrombocytopenic purpura patients.
AB  - Collagen-binding activity (CBA) and FRETS-VWF73 assays are widely adopted methods
      for the measurement of the plasmatic activity of ADAMTS13, the von Willebrand
      factor (VWF) cleaving-protease. Accurately assessing the severe deficiency of
      ADAMTS13 is important in the management of thrombotic thrombocytopenic purpura
      (TTP). However, non-concordant results between the two assays have been reported
      in a small but relevant percentage of TTP cases. We investigated whether CBA or
      FRETS-VWF73 assay reflects ADAMTS13 proteolytic activity in acquired TTP patients
      with non-concordant measurements. Twenty plasma samples with non-concordant
      ADAMTS13 activity results, <10% using FRETS-VWF73 and >=20% using CBA, and 11
      samples with concordant results, <10% using either FRETS-VWF73 and CBA assays,
      were analysed. FRETS-VWF73 was performed in the presence of 1.5 M urea. ADAMTS13
      activities were also measured under flow conditions and the VWF multimer pattern
      was defined in order to verify the presence of ultra-large VWF due to ADAMTS13
      deficiency. In FRETS-VWF73 assay with 1.5 M urea, ADAMTS13 activity significantly
      increased in roughly 50% of the samples with non-concordant results, whereas it
      remained undetectable in all samples with concordant measurements. Under flow
      conditions, all tested samples showed reduced ADAMTS13 activity. Finally, samples
      with non-concordant results showed a ratio of high molecular weight VWF multimers
      higher than normal. Our results support the use of FRETS-VWF73 over CBA assay for
      the assessment of ADAMTS13 severe deficiency and indicate urea as one cause of
      the observed differences. 

PMID- 24740646
TI  - Image of God, religion, spirituality, and life changes in breast cancer
      survivors: a qualitative approach.
AB  - Religion and spirituality are much studied coping mechanisms; however, their
      relationship to changes in behaviors, relationships, and goals is unclear. This
      study explored the impact of a breast cancer diagnosis on religion/faith and
      changes in behaviors, relationship, or goals. In this qualitative study, women,
      who participated in a larger, quantitative study, completed written responses to
      questions regarding the role of religion/faith in their lives, the impact of
      their diagnosis on their image of God and on faith/religious beliefs, and any
      changes in behaviors, relationships, or life goals were examined. Based on
      previous findings noting differences in psychological outcomes based on a higher
      (HE) or lesser (LE) engaged view of God, 28 (14 HE; 14 LE) women were included in
      the analysis. Awareness of life and its fleeting nature was common to all.
      Ensuing behaviors varied from a need to focus on self-improvement-egocentrism
      (LE)-to a need to focus on using their experiences to help others-altruism (HE).
      Study results suggest that seemingly small, but highly meaningful, differences
      based on one's worldview result in considerably different attitudinal and
      behavioral outcomes. 

PMID- 24740647
TI  - Premature termination of SMARCB1 translation may be followed by reinitiation in
      schwannomatosis-associated schwannomas, but results in absence of SMARCB1
      expression in rhabdoid tumors.
AB  - In schwannomatosis, germline SMARCB1 mutations predispose to the development of
      multiple schwannomas, but not vestibular schwannomas. Many of these are missense
      or splice-site mutations or in-frame deletions, which are presumed to result in
      the synthesis of altered SMARCB1 proteins. However, also nonsense and frameshift
      mutations, which are characteristic for rhabdoid tumors and are predicted to
      result in the absence of SMARCB1 protein via nonsense-mediated mRNA decay, have
      been reported in schwannomatosis patients. We investigated the consequences of
      four of the latter mutations, i.e. c.30delC, c.34C>T, c.38delA, and c.46A>T, all
      in SMARCB1-exon 1. We could demonstrate for the c.30delC and c.34C>T mutations
      that the respective mRNAs were still present in the schwannomas of the patients.
      We hypothesized that these were prevented from degradation by translation
      reinitiation at the AUG codon encoding methionine at position 27 of the SMARCB1
      protein. To test this, we expressed the mutations in MON cells, rhabdoid cells
      without endogenous SMARCB1 protein, and found that all four resulted in synthesis
      of the N-terminally truncated protein. Mutation of the reinitiation methionine
      codon into a valine codon prevented synthesis of the truncated protein, thereby
      confirming its identity. Immunohistochemistry with a SMARCB1 antibody revealed a
      mosaic staining pattern in schwannomas of the patients with the c.30delC and
      c.34C>T mutations. Our findings support the concept that, in contrast to the
      complete absence of SMARCB1 expression in rhabdoid tumors, altered SMARCB1
      proteins with modified activity and reduced (mosaic) expression are formed in the
      schwannomas of schwannomatosis patients with a germline SMARCB1 mutation. 

PMID- 24740648
TI  - Phase transition of [2,2]-paracyclophane--an end to an apparently endless story.
AB  - In this contribution, the solid-state low-temperature phase structure of [2,2]
      paracyclophane is unambiguously characterised by single-crystal X-ray analysis.
      Additionally, a heat capacity measurement was undertaken, which proves the
      existence of a lambda-type phase transition at 45 K, a transition that is
      connected with the formation of a secondary Cp/T feature at 60 K. The low
      temperature phase (<45 K) crystallises in the lower symmetry space group P4n2,
      whereas the high-temperature phase (>60 K) crystallises in space group P4(2)/mnm.
      This proves what has been postulated both by experimental and theoretical
      chemists but has repeatedly been dismissed as speculation many times.

PMID- 24740649
TI  - Systemic effects of polymethylmethycrylate in total knee replacement: A
      prospective case-control study.
AB  - OBJECTIVE: Mortality rates reported by the National Joint Registry for England
      and Wales (NJR) were higher following cemented total knee replacement (TKR)
      compared with uncemented procedures. The aim of this study is to examine and
      compare the effects of cemented and uncemented TKR on the activation of selected
      markers of inflammation, endothelium, and coagulation, and on the activation of
      selected cytokines involved in the various aspects of the systemic response
      following surgery. METHODS: This was a single centre, prospective, case-control
      study. Following enrolment, blood samples were taken pre-operatively, and further
      samples were collected at day one and day seven post-operatively. One patient in
      the cemented group developed a deep-vein thrombosis confirmed on ultrasonography
      and was excluded, leaving 19 patients in this cohort (mean age 67.4, (sd 10.62)),
      and one patient in the uncemented group developed a post-operative wound
      infection and was excluded, leaving 19 patients (mean age 66.5, (sd 7.82)).
      RESULTS: Both groups had a similar response with regards to the levels of C
      reactive protein (CRP), interleukin 6 (IL-6) and tumour necrosis factor-alpha
      (TNFalpha). CD40 levels rose significantly on the cemented group over day one to
      day seven compared with that of the uncemented group, which occurred over the
      first 24 hours. The CD14/42a levels demonstrated a statistically significant
      increase in the cemented group (p < 0.001 first 24 hours and p = 0.02 between
      days one and seven). CONCLUSIONS: The uncemented and cemented groups demonstrated
      significant changes in the various parameters measured at various time points but
      apart from CD14/42a levels, there was no significant difference in the serum
      markers of inflammation, coagulation and endothelial dysfunction following
      cemented TKR. Cite this article: Bone Joint Res 2014;3:108-16.

PMID- 24740650
TI  - Safety and efficacy of sorafenib in the treatment of advanced hepatocellular
      carcinoma: a single center experience.
AB  - Sorafenib is the standard treatment of patients with advanced hepatocellular
      carcinoma (HCC), with demonstrated outcome benefits in randomized clinical
      trials. We present a single-center experience with sorafenib with the aim to
      establish its efficacy and safety in daily clinical practice. A total of 62
      patients were treated with sorafenib 400 mg/12 h until disease progression or
      unacceptable toxicity. Response rates, incidence of adverse events, actuarial
      disease-free survival, and overall survival (OS) were estimated. Univariate and
      multivariate analyses of prognostic factors for survival were also performed.
      Median treatment duration was 92 days. A 43% disease control rate was achieved
      (partial response, 15% and disease stabilization, 28%). After a median follow-up
      of 24.1 months, the median progression-free survival and OS for the overall
      population were 5.8 and 6.7 months, respectively, with survival rates of 27% at 1
      year and 17 % at 2 years. The most common grade 3-4 adverse events were fatigue
      (19%), hand-foot syndrome (8%), hypertension (5%), and diarrhea (3%). The
      univariate analysis showed that patient performance status (PS), use of previous
      treatments, and albumin >3.5 g/dL were significant prognostic factors for
      survival. In the multivariate study, only PS, alcoholic etiology and albumin >3.5
      g/dL remained as independent predictors of survival. Sorafenib is a safe and
      moderately effective drug in HCC, although patients must be properly selected
      before starting therapy. Baseline PS, Barcelona Clinic Liver Cancer staging, and
      liver function should be taken into account as prognostic factors. Results in
      daily practice are somewhat inferior than observed in clinical trials.

PMID- 24740651
TI  - Co-existence of two different alpha-synuclein oligomers with different core
      structures determined by hydrogen/deuterium exchange mass spectrometry.
AB  - Neurodegenerative disorders are characterized by the formation of protein
      oligomers and amyloid fibrils, which in the case of Parkinson's disease involves
      the protein alpha-synuclein (alphaSN). Cytotoxicity is mainly associated with the
      oligomeric species, but we still know little about their assembly and structure.
      Hydrogen/deuterium exchange (HDX) monitored by mass spectrometry is used to
      analyze oligomers formed by wild-type (wt) alphaSN and also three familial
      alphaSN mutants (A30P, E46K, and A53T). All four variants show co-existence of
      two different oligomers. The backbone amides of oligomer type I are protected
      from exchange with D2 O until they dissociate into monomeric alphaSN by EX1
      exchange kinetics. Fewer residues are protected against exchange in oligomer type
      II, but this type does not revert to alphaSN monomers. Both oligomers are
      protected in the core sequence Y39-A89. Based on incubation studies, oligomer
      type I appears to form straight fibrils, while oligomer type II forms amorphous
      clusters that do not directly contribute to the fibrillation process. 

PMID- 24740652
TI  - Effect of vitamin D on bioavailability and lipid lowering efficacy of
      simvastatin.
AB  - The 3-hydroxy 3-methylglutaryl coenzyme A reductase (HMG-CoA reductase)
      inhibitors known as "statins" are widely prescribed for the management of
      dyslipidemia. In spite of their muscle toxicity, use of statins has alarmingly
      increased worldwide. A recent report suggests that vitamin D (VD) levels are
      closely associated with lipid lowering activity and muscular toxicity of statins.
      However, data are limited and inconclusive. The present study was undertaken to
      investigate the effect of VD supplementation on the bioavailability and lipid
      lowering effect of simvastatin (ST). Adult Sprague-Dawley male rats (250 +/- 10
      g) were divided into four groups including control, ST (100 mg/kg/day), VD (100
      MUg/kg/day) and ST + VD group, respectively. After the dosing period of 8 days
      the animals were sacrificed and the blood was collected for the analysis of ST,
      its active metabolite simvastatin acid (STA), total cholesterol, triglyceride and
      liver enzymes including aspartate transaminase and alanine transaminase. The
      result of this study showed a significant decrease in the level of cholesterol
      and triglyceride in ST alone treated group, whereas VD alone failed to alter the
      blood lipid levels. Concomitant treatment with VD produced significant decrease
      in the bioavailability of ST and STA. However, there was no significant
      difference in the level of cholesterol in ST alone and in ST + VD treated group.
      Our results on the liver enzyme suggest that ST alone or in combination with VD
      does not produce any hepatotoxicity. Further studies using VD along with various
      statins for a longer duration are suggested.

PMID- 24740653
TI  - The role of active muscle mass in determining the magnitude of peripheral fatigue
      during dynamic exercise.
AB  - Greater peripheral quadriceps fatigue at the voluntary termination of single-leg
      knee-extensor exercise (KE), compared with whole-body cycling, has been
      attributed to confining group III and IV skeletal muscle afferent feedback to a
      small muscle mass, enabling the central nervous system (CNS) to tolerate greater
      peripheral fatigue. However, as task specificity and vastly differing systemic
      challenges may have complicated this interpretation, eight males were studied
      during constant workload trials to exhaustion at 85% of peak workload during
      single-leg and double-leg KE. It was hypothesized that because of the smaller
      muscle mass engaged during single-leg KE, a greater magnitude of peripheral
      quadriceps fatigue would be present at exhaustion. Vastus lateralis integrated
      electromyogram (iEMG) signal relative to the first minute of exercise,
      preexercise to postexercise maximal voluntary contractions (MVCs) of the
      quadriceps, and twitch-force evoked by supramaximal magnetic femoral nerve
      stimulation (Qtw,pot) quantified peripheral quadriceps fatigue. Trials performed
      with single-leg KE (8.1 +/- 1.2 min; 45 +/- 4 W) resulted in significantly
      greater peripheral quadriceps fatigue than double-leg KE (10 +/- 1.3 min; 83 +/-
      7 W), as documented by changes in the iEMG signal (147 +/- 24 vs. 85 +/- 13%),
      MVC (-25 +/- 3 vs. -12 +/- 3%), and Qtw,pot (-44 +/- 6 vs. -33 +/- 7%), for
      single-leg and double-leg KE, respectively. Therefore, avoiding concerns over
      task specificity and cardiorespiratory limitations, this study reveals that a
      reduction in muscle mass permits the development of greater peripheral muscle
      fatigue and supports the concept that the CNS tolerates a greater magnitude of
      peripheral fatigue when the source of group III/IV afferent feedback is limited
      to a small muscle mass.

PMID- 24740654
TI  - Overexpression of TRB3 in muscle alters muscle fiber type and improves exercise
      capacity in mice.
AB  - Increasing evidence suggests that TRB3, a mammalian homolog of Drosophila
      tribbles, plays an important role in cell growth, differentiation, and
      metabolism. In the liver, TRB3 binds and inhibits Akt activity, whereas in
      adipocytes, TRB3 upregulates fatty acid oxidation. In cultured muscle cells, TRB3
      has been identified as a potential regulator of insulin signaling. However,
      little is known about the function and regulation of TRB3 in skeletal muscle in
      vivo. In the current study, we found that 4 wk of voluntary wheel running (6.6 +/
      0.4 km/day) increased TRB3 mRNA by 1.6-fold and protein by 2.5-fold in the
      triceps muscle. Consistent with this finding, muscle-specific transgenic mice
      that overexpress TRB3 (TG) had a pronounced increase in exercise capacity
      compared with wild-type (WT) littermates (TG: 1,535 +/- 283; WT: 644 +/- 67
      joules). The increase in exercise capacity in TRB3 TG mice was not associated
      with changes in glucose uptake or glycogen levels; however, these mice displayed
      a dramatic shift toward a more oxidative/fatigue-resistant (type I/IIA) muscle
      fiber type, including threefold more type I fibers in soleus muscles. Skeletal
      muscle from TRB3 TG mice had significantly decreased PPARalpha expression,
      twofold higher levels of miR208b and miR499, and corresponding increases in the
      myosin heavy chain isoforms Myh7 and Myb7b, which encode these microRNAs. These
      findings suggest that TRB3 regulates muscle fiber type via a peroxisome
      proliferator-activated receptor-alpha (PPAR-alpha)-regulated miR499/miR208b
      pathway, revealing a novel function for TRB3 in the regulation of skeletal muscle
      fiber type and exercise capacity.

PMID- 24740655
TI  - Amygdala mediates respiratory responses to sudden arousing stimuli and to
      restraint stress in rats.
AB  - Both human and animal studies have demonstrated that respiratory parameters
      change in response to presentation of alerting stimuli, as well as during stress,
      yet central neuronal pathways that mediate such responses remain unknown. The aim
      of our study was to investigate the involvement of the amygdala in mediating
      respiratory responses to stressors of various intensities and duration. Adult
      male Wistar rats (n = 8) received microinjections of GABAA agonist muscimol or
      saline into the amygdala bilaterally and were subjected to a respiratory
      recording using whole body plethysmography. Presentation of acoustic stimuli (500
      ms white noise, 40-90 dB) caused transient responses in respiratory rate that
      were proportional to the stimulus intensity, ranging from +13 +/- 9 cpm to +276
      +/- 67 cpm for 40- and 90-dB stimuli, respectively. Inhibition of the amygdala
      significantly suppressed respiratory rate responses to the high-intensity stimuli
      (70-90 dB). Submitting rats to the restraint stress significantly elevated the
      mean respiratory rate (+72 +/- 8 cpm) and the dominant respiratory rate (+51 +/-
      12 cpm), as well as the fraction of high-frequency respiratory rate (+10 +/- 3%).
      Inhibition of the amygdala by muscimol significantly suppressed these responses.
      We conclude that the amygdala is one of the key structures that are essential for
      expression of respiratory responses to stressful or alerting stimuli in rats.

PMID- 24740656
TI  - Exercise training enhances insulin-stimulated nerve arterial vasodilation in rats
      with insulin-treated experimental diabetes.
AB  - Insulin stimulates nerve arterial vasodilation through a nitric oxide (NO)
      synthase (NOS) mechanism. Experimental diabetes reduces vasa nervorum NO
      reactivity. Studies investigating hyperglycemia and nerve arterial vasodilation
      typically omit insulin treatment and use sedentary rats resulting in severe
      hyperglycemia. We tested the hypotheses that 1) insulin-treated experimental
      diabetes and inactivity (DS rats) will attenuate insulin-mediated nerve arterial
      vasodilation, and 2) deficits in vasodilation in DS rats will be overcome by
      concurrent exercise training (DX rats; 75-85% VO2 max, 1 h/day, 5 days/wk, for 10
      wk). The baseline index of vascular conductance values (VCi = nerve blood flow
      velocity/mean arterial blood pressure) were similar (P >= 0.68), but peak VCi and
      the area under the curve (AUCi) for the VCi during a euglycemic hyperinsulinemic
      clamp (EHC; 10 mU.kg(-1).min(-1)) were lower in DS rats versus control sedentary
      (CS) rats and DX rats (P <= 0.01). Motor nerve conduction velocity (MNCV) was
      lower in DS rats versus CS rats and DX rats (P <= 0.01). When compared with DS
      rats, DX rats expressed greater nerve endothelial NOS (eNOS) protein content (P =
      0.04). In a separate analysis, we examined the impact of diabetes in exercise
      trained rats alone. When compared with exercise-trained control rats (CX), DX
      rats had a lower AUCi during the EHC, lower MNCV values, and lower sciatic nerve
      eNOS protein content (P <= 0.03). Therefore, vasa nervorum and motor nerve
      function are impaired in DS rats. Such deficits in rats with diabetes can be
      overcome by concurrent exercise training. However, in exercise-trained rats (CX
      and DX groups), moderate hyperglycemia lowers vasa nervorum and nerve function.

PMID- 24740657
TI  - rhBMP use in cervical spine surgery: associated factors and in-hospital
      complications.
AB  - BACKGROUND: Widespread use of recombinant human bone morphogenetic protein
      (rhBMP) in cervical spine surgery has continued despite the U.S. Food and Drug
      Administration's 2008 notification regarding its adverse effects. Our study goals
      were to analyze how patient, surgical, and institutional factors influenced rhBMP
      use in cervical spinal fusion surgery and to examine the cervical-spine-specific
      in-hospital complications associated with rhBMP use. METHODS: The Nationwide
      Inpatient Sample database was used to identify 1,064,372 patients eighteen years
      or older who had undergone cervical spinal fusion surgery from 2003 through 2010.
      Of these patients, 84,726 (7.96%) received rhBMP. Multivariate logistic
      regression models were used to analyze patient, surgical, and institutional
      factors associated with rhBMP use, and the relationship between rhBMP use and the
      development of in-hospital complications. RESULTS: On multivariate analysis,
      patient age and sex, insurance type, surgical approach, use of autograft bone,
      and hospital teaching status, size, and region were significant predictors of
      rhBMP use. Use of rhBMP was a significant predictor of complications on
      univariate analysis and on multivariate analysis adjusted for patient age and
      sex, Charlson comorbidity score, insurance status, surgical approach, autograft
      bone use, and hospital teaching status, size, and region. Use of rhBMP was
      significantly associated with the development of dysphagia (prevalence, 2.0%;
      adjusted odds ratio [OR], 1.53), dysphonia (prevalence, 0.28%; adjusted OR,
      1.48), hematoma/seroma formation (prevalence, 0.7%; adjusted OR, 1.24), and
      neurological complications (prevalence, 0.84%; adjusted OR, 2.0). These
      complications were most commonly found after anterior cervical fusion surgery.
      Wound infections and neurological complications were most commonly found after
      posterior cervical fusion surgery. Dysphagia was most commonly found after
      circumferential fusion surgery. CONCLUSIONS: Indications for rhBMP use for
      cervical spinal fusion are multifactorial. Its use is associated with a
      significantly higher likelihood of cervical-spine-specific complications.

PMID- 24740658
TI  - Impact of the economic downturn on total joint replacement demand in the United
      States: updated projections to 2021.
AB  - BACKGROUND: Few studies have explored the role of the National Health Expenditure
      and macroeconomics on the utilization of total joint replacement. The economic
      downturn has raised questions about the sustainability of growth for total joint
      replacement in the future. Previous projections of total joint replacement demand
      in the United States were based on data up to 2003 using a statistical
      methodology that neglected macroeconomic factors, such as the National Health
      Expenditure. METHODS: Data from the Nationwide Inpatient Sample (1993 to 2010)
      were used with United States Census and National Health Expenditure data to
      quantify historical trends in total joint replacement rates, including the two
      economic downturns in the 2000s. Primary and revision hip and knee arthroplasty
      were identified using codes from the International Classification of Diseases,
      Ninth Revision, Clinical Modification. Projections in total joint replacement
      were estimated using a regression model incorporating the growth in population
      and rate of arthroplasties from 1993 to 2010 as a function of age, sex, race, and
      census region using the National Health Expenditure as the independent variable.
      The regression model was used in conjunction with government projections of
      National Health Expenditure from 2011 to 2021 to estimate future arthroplasty
      rates in subpopulations of the United States and to derive national estimates.
      RESULTS: The growth trend for the incidence of joint arthroplasty, for the
      overall United States population as well as for the United States workforce, was
      insensitive to economic downturns. From 2009 to 2010, the total number of
      procedures increased by 6.0% for primary total hip arthroplasty, 6.1% for primary
      total knee arthroplasty, 10.8% for revision total hip arthroplasty, and 13.5% for
      revision total knee arthroplasty. The National Health Expenditure model
      projections for primary hip replacement in 2020 were higher than a previously
      projected model, whereas the current model estimates for total knee arthroplasty
      were lower. CONCLUSIONS: Economic downturns in the 2000s did not substantially
      influence the national growth trends for hip and knee arthroplasty in the United
      States. These latest updated projections provide a basis for surgeons, hospitals,
      payers, and policy makers to plan for the future demand for total joint
      replacement surgery.

PMID- 24740659
TI  - Wait-and-see policy as a first-line management for extra-abdominal desmoid
      tumors.
AB  - BACKGROUND: Extra-abdominal desmoid tumors are rare, locally aggressive neoplasms
      without metastatic potential. There is no clear consensus regarding their optimal
      management. The disappointing results of current treatments and the ability of
      extra-abdominal desmoid tumors to spontaneously stabilize have increasingly drawn
      interest toward conservative management. The objective of this study was to
      evaluate a wait-and-see policy as a first-line management for extra-abdominal
      desmoid tumors. METHODS: This two-center retrospective study involved fifty-five
      patients with a histologically proven extra-abdominal desmoid tumor. The primary
      outcome was the cumulative probability of dropping out from the wait-and-see
      policy. The wait-and-see policy included aggressive management of symptoms. We
      conducted a review of the relevant published series in which a watchful-waiting
      strategy was used. RESULTS: The cumulative probability of dropping out from the
      wait-and-see policy was 9.6% at the time of the last follow-up. Spontaneous
      arrest of tumor growth was noted for forty-seven patients (85%) over the course
      of the study. Half of the tumors were stabilized at one year, and a potential to
      increase beyond three years was a sporadic event (one case). Regrowth was found
      in two patients (4%). CONCLUSIONS: A wait-and-see policy is an effective front
      line management for patients with primary or recurrent extra-abdominal desmoid
      tumor. These tumors tend to stabilize spontaneously, on average after one year of
      evolution, and the cumulative probability of the failure of a wait-and-see policy
      is approximately 10%.

PMID- 24740660
TI  - Variation in hospital-level risk-standardized complication rates following
      elective primary total hip and knee arthroplasty.
AB  - BACKGROUND: Little is known about the variation in complication rates among U.S.
      hospitals that perform elective total hip arthroplasty (THA) and total knee
      arthroplasty (TKA) procedures. The purpose of this study was to use National
      Quality Forum (NQF)-endorsed hospital-level risk-standardized complication rates
      to describe variations in, and disparities related to, hospital quality for
      elective primary THA and TKA procedures performed in U.S. hospitals. METHODS: We
      conducted a cross-sectional analysis of national Medicare Fee-for-Service data.
      The study cohort included 878,098 Medicare fee-for-service beneficiaries, sixty
      five years or older, who underwent elective THA or TKA from 2008 to 2010 at 3479
      hospitals. Both medical and surgical complications were included in the composite
      measure. Hospital-specific complication rates were calculated from Medicare
      claims with use of hierarchical logistic regression to account for patient
      clustering and were risk-adjusted for age, sex, and patient comorbidities. We
      determined whether hospitals with higher proportions of Medicaid patients and
      black patients had higher risk-standardized complication rates. RESULTS: The
      crude rate of measured complications was 3.6%. The most common complications were
      pneumonia (0.86%), pulmonary embolism (0.75%), and periprosthetic joint infection
      or wound infection (0.67%). The median risk-standardized complication rate was
      3.6% (range, 1.8% to 9.0%). Among hospitals with at least twenty-five THA and TKA
      patients in the study cohort, 103 (3.6%) were better and seventy-five (2.6%) were
      worse than expected. Hospitals with the highest proportion of Medicaid patients
      had slightly higher but similar risk-standardized complication rates (median,
      3.6%; range, 2.0% to 7.1%) compared with hospitals in the lowest decile (3.4%;
      1.7% to 6.2%). Findings were similar for the analysis involving the proportion of
      black patients. CONCLUSIONS: There was more than a fourfold difference in risk
      standardized complication rates across U.S. hospitals in which elective THA and
      TKA are performed. Although hospitals with higher proportions of Medicaid and
      black patients had rates similar to those of hospitals with lower proportions,
      there is a continued need to monitor for disparities in outcomes. These findings
      suggest there are opportunities for quality improvement among hospitals in which
      elective THA and TKA procedures are performed.

PMID- 24740661
TI  - Bracing for idiopathic scoliosis: how many patients require treatment to prevent
      one surgery?
AB  - BACKGROUND: Although the efficacy of bracing for adolescent idiopathic scoliosis
      has been debated, recent evidence indicates a strong dose-response effect with
      respect to preventing curve progression of >=6 degrees . The purpose of this
      study was to investigate whether bracing, prescribed with use of current
      criteria, prevents surgery and how many patients must be treated with bracing to
      prevent one surgery. METHODS: Of 126 patients with adolescent idiopathic
      scoliosis measuring between 25 degrees  and 45 degrees  and with a Risser sign of
      <=2, 100 completed a prospective study in which they were managed with a Boston
      brace fitted with a heat sensor that measured brace wear. Noncompliant patients
      were compared both with highly compliant patients and with the entire cohort,
      with the end point of progression to surgery. The absolute risk reduction (ARR)
      was calculated and used to calculate the number needed to treat (NNT) to prevent
      one surgery. RESULTS: Bracing was not effective in preventing surgery unless the
      patient was highly compliant with brace wear. For patients who were considered to
      be highly compliant, based on the hours per day that they wore the brace, the NNT
      was 3 (95% confidence interval [CI], 2 to 7). CONCLUSIONS: Within the limitations
      of a nonrandomized prospective study design, bracing for adolescent idiopathic
      scoliosis was found to substantially decrease the risk of curve progression to a
      range requiring surgery when patients were highly compliant with brace wear.
      Since many patients avoid surgery without wearing a brace, current indications
      appear to lead to marked overtreatment. Bracing appears to decrease the risk of
      curve progression to a magnitude requiring surgery, but current bracing
      indications include many curves that would not have progressed to a magnitude
      requiring surgery even if the patient had not worn the brace, and overall
      compliance with brace wear is low. Identifying these lower-risk patients and
      improving the compliance of those likely to have curve progression could
      substantially improve bracing results.

PMID- 24740662
TI  - High-dosage tamoxifen as neoadjuvant treatment in minimally invasive surgery for
      Dupuytren disease in patients with a strong predisposition toward fibrosis: a
      randomized controlled trial.
AB  - BACKGROUND: Tamoxifen, a synthetic nonsteroidal anti-estrogen known to modulate
      the production of transforming growth factor-beta (TGF-beta), has demonstrated
      effectiveness on fibroblast activity in vitro and in vivo. The main purpose of
      this study was to investigate the effect of tamoxifen on the outcome of surgery
      for Dupuytren contractures in patients with a strong predisposition toward
      fibrosis. METHODS: We used a prospective, randomized, double-blind study protocol
      (conforming to the CONSORT standards) to investigate the influence of tamoxifen
      compared with placebo on the total passive extension deficit in the finger and
      patient satisfaction after subtotal fasciectomy in thirty patients with a strong
      predisposition toward fibrosis (grade, >4 according to the Abe scale). High
      dosage tamoxifen (80 mg/day) was administered from six weeks prior until twelve
      weeks after surgery, and patients were monitored for two years. RESULTS: Three
      months after surgery, patients in the tamoxifen group had a smaller total passive
      extension deficit and higher satisfaction compared with the placebo group. This
      positive effect was lost over the two years following cessation of the
      medication. CONCLUSIONS: This study demonstrated that the short-term outcome of
      Dupuytren disease treatment could be influenced by use of tamoxifen as a
      neoadjuvant from six weeks prior to three months after subtotal fasciectomy in
      patients with a strong predisposition toward fibrosis. However, the beneficial
      effect disappeared within two years after surgery, with worsening of the
      contractures after the medication was discontinued. Thus, tamoxifen may have a
      short-term effect on the outcome of surgery for Dupuytren disease.

PMID- 24740663
TI  - Anatomic single-bundle ACL reconstruction is possible with use of the modified
      transtibial technique: a comparison with the anteromedial transportal technique.
AB  - BACKGROUND: Anatomic anterior cruciate ligament (ACL) reconstruction is essential
      to the restoration of normal knee kinematics and to achieving successful results
      after ACL surgery. The purpose of this study was to evaluate whether anatomic
      single-bundle ACL reconstruction can be performed with use of the modified
      transtibial technique such that the tunnel characteristics are not substantially
      different from those of the anteromedial transportal technique, with comparable
      clinical results. METHODS: One hundred and four patients underwent single-bundle
      ACL reconstruction performed with use of either the modified transtibial
      technique or the anteromedial transportal technique. Each group included fifty
      two patients retrospectively matched on the basis of age, sex, and body mass
      index. All patients had postoperative computed tomography (CT) and a minimum
      duration of follow-up of twenty-four-months. CT parameters, including tunnel
      position, tunnel length and shape, and graft obliquity, were evaluated. Clinical
      assessments were based on manual laxity tests, arthrometric analysis, and
      clinical scores recorded preoperatively and at the time of follow-up. RESULTS:
      The femoral tunnel was placed at a slightly inferior and anterior position with
      use of the modified transtibial technique compared with the anteromedial
      transportal technique, but the difference was not significant (superior-inferior
      mean [and standard deviation], 35.7% +/- 3.1% versus 33.9% +/- 4.1%, p > 0.05,
      and anterior-posterior mean, 31.6 +/- 6.8% versus 35.1 +/- 6.9%, p > 0.05, as
      assessed with use of the quadrant method). The femoral tunnel length was
      significantly longer (p < 0.05) and the tibial tunnel length was significantly
      shorter (p < 0.05) with use of the modified transtibial technique compared with
      the anteromedial transportal technique (mean femoral tunnel length, 40.5 +/- 4.2
      mm versus 34.4 +/- 2.6 mm and mean tibial tunnel length, 32.3 +/- 3.1 mm versus
      35.5 +/- 2.7 mm); however, tunnel length was sufficient to allow for adequate
      fixation. There were no significant differences between the two groups in terms
      of tibial tunnel position, graft obliquity, tibial tunnel widening, and clinical
      results. CONCLUSIONS: Tunnel characteristics including anatomic position, graft
      obliquity, and tunnel widening after single-bundle ACL reconstruction performed
      with use of the modified transtibial technique were not significantly different
      from those of the anteromedial transportal technique, and clinical results were
      comparable.

PMID- 24740664
TI  - Cigarette smoking increases complications following fracture: a systematic
      review.
AB  - BACKGROUND: Smoking has been suggested to increase the rate of perioperative
      complications including soft-tissue complications, to decrease the rate of
      fracture union, and to prolong healing time. The purpose of our study was to
      systematically evaluate and analyze the literature regarding the relationship
      between smoking and healing following operative treatment of long-bone fractures.
      METHODS: We searched the MEDLINE, Embase, and Cochrane databases by pairing the
      search terms "smoking," "tobacco," and "nicotine" with the terms "fracture,"
      "nonunion," delayed union," and "healing." Articles and citations were evaluated
      for relevance. Inclusion and exclusion criteria were established to maintain data
      quality for analysis. Relevant information was independently extracted and
      compared to ensure agreement. The methodological quality of the studies was
      determined. A random-effects model was used. The adjusted odds ratios (ORs) and
      frequency-weighted means for the primary and secondary outcome measures were
      calculated. RESULTS: Our initial search identified 7110 articles. Of the 237
      articles that underwent further evaluation of the abstract, nineteen (seven
      prospective and twelve retrospective cohort studies) were included. The adjusted
      OR of nonunion in the smoking group compared with the nonsmoking group was 2.32
      (95% confidence interval [CI], 1.76 to 3.06; p < 0.001). An increased nonunion
      rate was observed in smokers with a tibial fracture (OR, 2.16; 95% CI, 1.55 to
      3.01; p < 0.001) and those with an open fracture (OR, 1.95; 95% CI, 1.3 to 2.9; p
      < 0.001). For all fractures, the mean healing time was longer for smokers (30.2
      weeks; 95% CI, 22.7 to 37.7 weeks) than for nonsmokers (24.1 weeks; 95% CI, 17.3
      to 30.9 weeks) (p = 0.18). Trends toward more superficial and deep infections of
      postoperative or traumatic wounds in smokers were noted; however, the differences
      in superficial and deep infection rates were not significant (p = 0.13 and p =
      0.33, respectively). CONCLUSIONS: Smoking significantly increased the risk of
      nonunion of fractures overall, tibial fractures, and open fractures.
      Nonsignificant trends toward increased time to union in all fractures and toward
      increased postoperative rates of superficial and deep infections were noted in
      smokers compared with nonsmokers.

PMID- 24740665
TI  - The American Academy of Orthopaedic Surgeons appropriate use criteria on
      optimizing the management of full-thickness rotator cuff tears.

PMID- 24740666
TI  - Operative treatment of primary anterior cruciate ligament rupture in adults.
AB  - Operative management of an acute anterior cruciate ligament (ACL) rupture may be
      required in young and active patients to stabilize the knee and return patients
      to desired daily activities. ACL reconstruction should be performed anatomically.
      The majority of studies show no differences between anatomic single-bundle and
      double-bundle ACL reconstruction with respect to patient-reported outcome scores.
      Double-bundle reconstruction may provide superior knee joint laxity measurements
      compared with the single-bundle technique. Following ACL reconstruction, the age
      and activity level of a patient are predictive of his or her time of return to
      sports and reinjury. Concomitant meniscal and/or cartilage damage at the time of
      surgery, in addition to a persistent knee motion deficit, are associated with the
      development of osteoarthritis after ACL reconstruction.

PMID- 24740667
TI  - What's new in sports medicine.

PMID- 24740668
TI  - Prognostic effect of erroneous surgical procedures in patients with osteosarcoma:
      evaluation using propensity score matching.
AB  - BACKGROUND: Little is known concerning erroneous surgical procedures of malignant
      bone tumors, and the prognostic effect of erroneous surgical procedures in
      osteosarcoma has not been determined. METHODS: We retrospectively reviewed 240
      patients with initially non-metastatic high-grade osteosarcoma of the pelvis and
      extremities and, of these, identified twenty-six who had undergone previous less
      appropriate surgical procedures due to misdiagnosis followed by adequate
      treatment at our institution. We evaluated the clinicopathologic characteristics
      of these twenty-six patients compared with the remaining 214 patients treated
      with regular protocol. Subsequently, thirty-eight patients (nineteen in the
      matched case group and nineteen in the matched control group) were matched for
      multiple different variables using propensity score matching, and the oncologic
      results in terms of event-free survival and overall survival were analyzed.
      RESULTS: The patients undergoing erroneous surgical procedures were typically
      older, with small, non-osteoblastic-type tumors that were in an unusual location,
      showed an osteolytic pattern on radiographs, had a tendency toward marginal or
      intralesional excision with positive histologic margin, and had not been treated
      with neoadjuvant chemotherapy (all p < 0.05). After adjustment of confounding
      variables by propensity score matching, there was no significant difference
      between matched groups with regard to event-free survival (p = 0.46) and overall
      survival (p = 0.99). CONCLUSIONS: Distinct differences existed in the
      clinicopathologic characteristics of the patients who underwent erroneous
      surgical procedures due to misdiagnosis. We failed to detect a prognostic
      relevance of the presence of previous erroneous procedures followed by adequate
      treatment.

PMID- 24740669
TI  - Body image in patients with adolescent idiopathic scoliosis: validation of the
      Body Image Disturbance Questionnaire--Scoliosis Version.
AB  - BACKGROUND: Appearance concerns in individuals with adolescent idiopathic
      scoliosis can result in impairment in daily functioning, or body image
      disturbance. The Body Image Disturbance Questionnaire (BIDQ) is a self-reported,
      seven-question instrument that measures body image disturbance in general
      populations; no studies have specifically examined body image disturbance in
      those with adolescent idiopathic scoliosis. This study aimed to validate a
      modified version of the BIDQ in a population with adolescent idiopathic scoliosis
      and to establish discriminant validity by comparing responses of operatively and
      nonoperatively treated patients with those of normal controls. METHODS: In the
      first phase, a multicenter study of forty-nine patients (mean age, fourteen
      years; thirty-seven female) with adolescent idiopathic scoliosis was performed to
      validate the BIDQ-Scoliosis version (BIDQ-S). Participants completed the BIDQ-S,
      Scoliosis Research Society (SRS)-22, Children's Depression Index (CDI), and Body
      Esteem Scale for Adolescents and Adults (BESAA) questionnaires. Descriptive
      statistics and Pearson correlation coefficients were calculated. In the second
      phase, ninety-eight patients with adolescent idiopathic scoliosis (mean age, 15.7
      years; seventy-five female) matched by age and sex with ninety-eight healthy
      adolescents were enrolled into a single-center study to evaluate the discriminant
      validity of the BIDQ-S. Subjects completed the BIDQ-S and a demographic form
      before treatment. Independent-sample t tests and Pearson correlation coefficients
      were calculated. RESULTS: The BIDQ-S was internally consistent (Cronbach alpha =
      0.82), and corrected item total correlations ranged from 0.47 to 0.67. The BIDQ-S
      was significantly correlated with each domain of the SRS-22 and the total score
      (r = -0.50 to -0.72, p <= 0.001), with the CDI (r = 0.31, p = 0.03), and with the
      BESAA (r = 0.60, p < 0.001). BIDQ-S scores differed significantly between
      patients (1.50) and controls (1.06, p < 0.005), establishing discriminant
      validity. CONCLUSIONS: The BIDQ-S is an internally consistent outcomes instrument
      that correlated with the SRS-22, CDI, and BESAA outcomes instruments in a
      scoliosis population. The scores of the patients with scoliosis indicated greater
      back-related body image disturbance compared with healthy controls. To our
      knowledge, this user-friendly instrument is the first to examine body image
      disturbance in adolescent idiopathic scoliosis, and it provides a comprehensive
      evaluation of how scoliosis-related appearance concerns impact psychosocial and
      daily functioning.

PMID- 24740670
TI  - The ligament anatomy of the deltoid complex of the ankle: a qualitative and
      quantitative anatomical study.
AB  - BACKGROUND: The deltoid ligament has both superficial and deep layers and
      consists of up to six ligamentous bands. The prevalence of the individual bands
      is variable, and no consensus as to which bands are constant or variable exists.
      Although other studies have looked at the variance in the deltoid anatomy, none
      have quantified the distance to relevant osseous landmarks. METHODS: The deltoid
      ligaments from fourteen non-paired, fresh-frozen cadaveric specimens were
      isolated and the ligamentous bands were identified. The lengths, footprint areas,
      orientations, and distances from relevant osseous landmarks were measured with a
      three-dimensional coordinate measurement device. RESULTS: In all specimens, the
      tibionavicular, tibiospring, and deep posterior tibiotalar ligaments were
      identified. Three additional bands were variable in our specimen cohort: the
      tibiocalcaneal, superficial posterior tibiotalar, and deep anterior tibiotalar
      ligaments. The deep posterior tibiotalar ligament was the largest band of the
      deltoid ligament. The origins from the distal center of the intercollicular
      groove were 16.1 mm (95% confidence interval, 14.7 to 17.5 mm) for the
      tibionavicular ligament, 13.1 mm (95% confidence interval, 11.1 to 15.1 mm) for
      the tibiospring ligament, and 7.6 mm (95% confidence interval, 6.7 to 8.5 mm) for
      the deep posterior tibiotalar ligament. Relevant to other pertinent osseous
      landmarks, the tibionavicular ligament inserted at 9.7 mm (95% confidence
      interval, 8.4 to 11.0 mm) from the tuberosity of the navicular, the tibiospring
      inserted at 35% (95% confidence interval, 33.4% to 36.6%) of the spring
      ligament's posteroanterior distance, and the deep posterior tibiotalar ligament
      inserted at 17.8 mm (95% confidence interval, 16.3 to 19.3 mm) from the
      posteromedial talar tubercle. CONCLUSIONS: The tibionavicular, tibiospring, and
      deep posterior tibiotalar ligament bands were constant components of the deltoid
      ligament. The deep posterior tibiotalar ligament was the largest band of the
      deltoid ligament. CLINICAL RELEVANCE: The anatomical data regarding the deltoid
      ligament bands in this study will help to guide anatomical placement of repairs
      and reconstructions for deltoid ligament injury or instability.

PMID- 24740671
TI  - Comparison of deformity with respect to the talus in patients with posterior
      tibial tendon dysfunction and controls using multiplanar weight-bearing imaging
      or conventional radiography.
AB  - BACKGROUND: Posterior tibial tendon dysfunction varies in location and severity.
      Weight-bearing radiographs have been validated to assess posterior tibial tendon
      dysfunction, yet their two-dimensional nature and the inability of the patients
      to achieve full weight-bearing during acquisition are limitations. Multiplanar
      modified sectional weight-bearing imaging is a novel modality, yielding computed
      tomography-like images compared with radiographs, yet with true weight-bearing,
      shorter acquisition time, and lower radiation. The aim of this study was to test
      two hypotheses: first, multiplanar weight-bearing imaging would localize
      deformity with respect to the talus in patients with posterior tibial dysfunction
      compared with controls, and second, multiplanar weight-bearing imaging would
      correlate with specific radiographic parameters of posterior tibial tendon
      dysfunction on weight-bearing radiographs. METHODS: Weight-bearing radiographs
      and multiplanar modified sectional weight-bearing images of the foot and ankle
      were made for twenty-three patients with flexible posterior tibial tendon
      dysfunction. Ten patients with imaging for unrelated pathological conditions
      served as controls. Thirteen radiographic parameters on the transverse, sagittal,
      and coronal views of multiplanar weight-bearing imaging in the study group were
      evaluated and compared with those in the control group. The same parameters on
      standing weight-bearing radiographs of patients in the study group were compared
      with those in the control group. RESULTS: Significant differences between study
      and control groups were found on multiplanar weight-bearing imaging for six of
      thirteen radiographic parameters (p < 0.05), notably the sagittal talonavicular
      angle as well as sagittal and transverse talar-first metatarsal angles (p =
      0.027, p = 0.003, and p = 0.004, respectively). However, only one parameter on
      weight-bearing radiographs (lateral talar-first metatarsal angle) reached
      significance (p < 0.05). Correlation showed excellent, very good, and good
      agreement between both imaging modalities for three, two, and five parameters,
      respectively. CONCLUSIONS: Deformity with respect to the talus in posterior
      tibial tendon dysfunction is multifactorial, but was notably seen at the
      talonavicular joint in the sagittal plane with both modalities. Good to excellent
      agreement was found between weight-bearing radiographs and multiplanar weight
      bearing images for many parameters; however, a greater number of significant
      differences was found between the flatfoot and control groups for multiplanar
      weight-bearing images. This implies a potential role for multiplanar modified
      sectional weight-bearing imaging as a more informative tool to assess posterior
      tibial tendon dysfunction in the physiological, full weight-bearing position.

PMID- 24740672
TI  - 3D CT assessment of the relationship between humeral head alignment and glenoid
      retroversion in glenohumeral osteoarthritis.
AB  - BACKGROUND: Glenoid bone loss associated with advanced glenohumeral arthritis is
      frequently accompanied by subluxation of the humeral head with subsequent
      inferior outcomes of shoulder arthroplasty. We hypothesized that the relationship
      between the center of the humeral head and the perpendicular to the glenoid fossa
      plane differs from, and is independent of, the relationship between the center of
      the humeral head and the plane of the scapula. METHODS: Three-dimensional
      computed tomography (3D CT) imaging was performed on sixty patients with advanced
      osteoarthritis and fifteen controls with no osteoarthritis to define the baseline
      relationship between the center of the humeral head and the perpendicular to the
      glenoid fossa plane and the plane of the scapula. Correlations between these
      variables and the amount of bone loss and glenoid version were assessed. RESULTS:
      There was a strong linear relationship (p < 0.001) between glenoid retroversion
      and the center of the humeral head in relation to the center line of the scapula
      (humeral-scapular alignment). Humeral head alignment in relation to the glenoid
      plane (humeral-glenoid alignment) was variable and not strongly correlated with
      the amount of glenoid retroversion. The average glenoid retroversion for the
      normal shoulders was -3.5 degrees , and the average humeral-scapular alignment
      offset percentage was -2.3%. The average humeral-glenoid alignment offset for the
      normal shoulders was 0.5 mm with an average humeral-glenoid alignment offset
      percentage of 0.9%. CONCLUSIONS: The location of the humeral head in relation to
      the glenoid can be defined as displacement from the plane of the scapula and from
      the perpendicular of the glenoid plane. These two measures are independent of one
      another. The data suggest that each measurement may represent a different effect
      on glenoid loading. CLINICAL RELEVANCE: The importance of this study is that it
      presents quantitative data and clear guidelines to define two measurements of
      glenohumeral alignment as separate and important variables. The clinical
      relevance of these methods will be further defined when they are correlated with
      clinical outcomes.

PMID- 24740673
TI  - Bipolar fresh total osteochondral allograft: why, where, when: AAOS exhibit
      selection.

PMID- 24740674
TI  - The 2013 American-British-Canadian Traveling Fellowship: innovation,
      accountability, and insight.

PMID- 24740675
TI  - How do we interpret national inpatient sample data about complications?
      Commentary on an article by Amit Jain, MD, et al.: "rhBMP Use in Cervical Spine
      Surgery: Associated Factors and In-hospital Complications".

PMID- 24740676
TI  - Updated projections of total joint arthroplasty demands in America. Commentary on
      an article by Steven M. Kurtz, PhD, et al.: "Impact of the Economic Downturn on
      Total Joint Replacement Demand in the United States. Updated Projections to
      2021".

PMID- 24740677
TI  - Is hope a method? Commentary on an article by Sylvain Briand, MD, et al.: "Wait
      and-See Policy as a First-Line Management for Extra-Abdominal Desmoid Tumors".

PMID- 24740678
TI  - Effective dehydrogenation of 2-pyridylmethanol derivatives catalyzed by an iron
      complex.
AB  - An unprecedented iron complex-catalyzed dehydrogenation of alcohols was achieved
      using CpFe(CO)2Cl with a base or CpFe(CO)(Py)(Ph) as a catalyst without
      sacrificing the hydrogen acceptors. This reaction effectively (up to TON 67,000)
      converted 2-pyridylmethanol derivatives to the corresponding ketones or
      aldehydes. The mechanistic study is also discussed.

PMID- 24740679
TI  - Association between diabetes mellitus and angina after acute myocardial
      infarction: analysis of the TRIUMPH prospective cohort study.
AB  - AIMS: While patients with diabetes mellitus (DM) have more extensive coronary
      disease and worse survival after acute myocardial infarction (AMI) than patients
      without DM, data on whether they experience more angina are conflicting. METHODS:
      We examined angina prevalence over the year following AMI among 3367 patients,
      including 1080 (32%) with DM, from 24 US hospitals enrolled in the TRIUMPH
      registry from 2005 to 2008. RESULTS: Patients with vs. without DM were more
      likely to be treated with antianginal medications both at discharge and over
      follow up. Despite more aggressive angina therapy, patients with vs. without DM
      had higher prevalence and severity of angina prior to AMI (49 vs. 43%, p = 0.001)
      and at each follow-up assessment, although rates of angina declined in both
      groups over time. In a hierarchical, multivariable, repeated-measures model that
      adjusted for multiple demographic and clinical factors including severity of
      coronary disease and in-hospital revascularization, DM was associated with a
      greater odds of angina over the 12 months of follow up; this association
      increased in magnitude over time (12-month OR 1.18, 95% CI 1.01-1.37; DM*time
      pinteraction = 0.008). CONCLUSIONS: Contrary to conventional wisdom, angina is
      more prevalent and more severe among patients with DM, both prior to and
      following AMI. This effect is amplified over time and independent of patient and
      treatment factors, including the presence of multivessel disease and coronary
      revascularization. This increased burden of angina may be due to more diffuse
      nature of coronary disease, more rapid progression of coronary disease over time,
      or greater myocardial demand among DM patients.

PMID- 24740680
TI  - Protocadherin 10 suppresses tumorigenesis and metastasis in colorectal cancer and
      its genetic loss predicts adverse prognosis.
AB  - Protocadherin 10 (PCDH10), a novel tumor suppressor gene in human cancers, is
      located in a common deleted region at chromosome 4q28 in colorectal cancer (CRC).
      This study aimed to ascertain the genetic loss of PCDH10 and its clinical
      relevance in CRC and to explore the tumor suppressor function of PCDH10. The
      genetic deletion of PCDH10 was determined in 171 pairs of primary tumors and
      corresponding normal mucosae by loss of heterozygosity study. In total, 53
      carcinomas were positive for allelic loss of PCDH10. The genetic aberration was
      significantly associated with tumor progression and distant metastasis (p = 0.021
      and p = 0.018, respectively) and was an independent predictor of poor survival
      for CRC patients (p = 0.005). Expression of PCDH10 gene was silenced or markedly
      down-regulated in all of 12 CRC cell lines tested and in 41 of 53 colorectal
      carcinomas compared with their matched normal mucosae. Ectopic expression of
      PCDH10 suppressed cancer cell proliferation, anchorage-independent growth,
      migration and invasion in vitro. Subcutaneous injection of PCDH10-expressing CRC
      cells into SCID mice revealed the reduction of tumor growth compared with that
      observed in mock-inoculated mice. Furthermore, through intrasplenic implantation,
      the re-expression of PCDH10 in silenced cells restrained liver metastasis and
      improved survival in SCID mice. In conclusion, PCDH10 is a pivotal tumor
      suppressor in CRC, and the loss of its function promotes not only tumor
      progression but also liver metastasis. In addition, the genetic deletion of
      PCDH10 represents an adverse prognostic marker for the survival of patients with
      CRC.

PMID- 24740681
TI  - NLRPs, microbiota, and gut homeostasis: unravelling the connection.
AB  - Within the NOD-like receptor (NLR) family, there are several NLRP (NLR family,
      pyrin domain-containing) proteins that are involved in the formation of
      inflammasomes. These multi-protein complexes are a key part of the network of
      cellular events required for secretion of the pro-inflammatory cytokines IL-1beta
      and IL-18. The NLRP3 inflammasome is the best-characterized member of the family
      and has recently been implicated in gut homeostasis and determining the severity
      of inflammation in inflammatory bowel disease (IBD) and inflammation-associated
      colorectal cancer. This led to the discovery that NLRP6 and NLRP12 also
      contribute to the maintenance of intestinal homeostasis and modulation of the gut
      microbiota, which in turn influences the intestine and distant organs. In this
      review, we bring together the latest data on the potential roles of NLRP family
      members in gut health and disease and identify the most pressing questions that
      remain to be answered to further our understanding of human diseases including
      IBD, inflammation-associated cancers, and metabolic syndromes linked with
      obesity.

PMID- 24740683
TI  - Feasibility and safety of transradial coronary interventions using a 6.5-F
      sheathless guiding catheter in patients with small radial arteries.
AB  - OBJECTIVES: This study investigated the feasibility and the safety of using a 6.5
      French sheathless guide catheter in patients with small radial arteries.
      BACKGROUND: The small size of radial arteries is a limitation of transradial
      coronary intervention. A new sheathless guiding catheter with a diameter almost 2
      Fr smaller than conventional sheaths and a full-length hydrophilic coating has
      been introduced. METHODS: A total of 148 patients from three French hospitals
      were consecutively enrolled from March 2009 to February 2012. They underwent
      transradial approach (TRA) for percutaneous coronary interventions (PCI) using
      the 6.5-F ASAHI sheathless Eaucath guiding catheter system. RESULTS: Among the
      148 patients enrolled, 95 were females (64%), and 183 lesions were treated.
      Procedural success rate was 100%. Thirteen patients (9%) underwent same-procedure
      multivessel interventions for the right and left coronary artery. Among the group
      of 46 patients undergoing bifurcation PCI, 35 (76%) bifurcated lesions were
      treated with a kissing balloon technique, one patient had a saphenous vein bypass
      graft lesion requiring filter wire placement prior to intervention, nine (6.1%)
      patients required rotational atherectomy, thrombus-aspiration catheters were used
      in 19 (12.8%) patients, fractional flow reserve (FFR)-guided PCI in 10 (6.7%)
      patients, alcohol septal ablation in three (2%) patients. Ten (6.7%) cases of
      chronic total occlusion were successfully treated in nine (6.1%) patients using
      the hydrophilic catheter. No radial artery site complications was noted.
      CONCLUSION: The use of sheathless guiding catheters is a safe, effective method
      for PCI via TRA in small radial arteries without catheter-related complications.

PMID- 24740682
TI  - New insights into p53 functions through its target microRNAs.
AB  - The tumor suppressor p53 pathway, whose alterations are highly associated with
      all types of human cancers, plays an essential role in preventing tumor
      development and progression mostly through its downstream target genes. Over the
      last decade, a growing list of p53 microRNA (miRNA) targets has been identified
      as additional downstream players of this pathway. Further studies of these miRNAs
      have revealed their more complicated regulations and functions in executing
      and/or regulating p53 activity. Here, we review the p53 miRNA targets identified
      thus far, and discuss how they fine-tune p53 stress responses, mediate the
      crosstalk between p53 and other signaling pathways, and expand the role of p53 in
      other human diseases in addition to cancers. 

PMID- 24740685
TI  - Gender as a disease modifier in neurofibromatosis type 1 optic pathway glioma.

PMID- 24740684
TI  - The role of clinical response to metformin in patients newly diagnosed with type
      2 diabetes: a monotherapy study.
AB  - A major predicament in certain users of metformin, which is one of the most
      commonly used antihyperglycemic agents for type 2 diabetes (T2DM) treatment, is
      the lack of appropriate response to the drug. We evaluated the role of metformin
      response and OCT1 (organic cation transporter1) Met420del polymorphism in a
      monotherapy study (metformin therapy for 12 weeks) on patients newly diagnosed
      with T2DM. Based on the response to metformin, patients (n = 108) were divided
      into two groups: responders (n = 49) and non-responders (n = 59). HbA1c levels
      were determined by affinity technique. The OCT1-Met420del polymorphism was
      genotyped by PCR-based restriction fragment length polymorphism. There was a
      significant association between the variable response with HbA1c and fasting
      blood sugar (FBS) (Wilks' lambda = 0.905, p = 0.01). Responders had significantly
      lower HbA1c and FBS levels compared with non-responders (eta (2) = 0.087, p =
      0.004 for HbA1c and eta (2) = 0.055, p = 0.022 for FBS). The interaction
      treatment-response increased the effect sizes from 32 to 58 % for HbA1c. Alanine
      aminotransferase (ALT) and aspartate aminotransferase (AST) values were
      significantly lower in the responder group than in the non-responders (eta (2) =
      0.067, p = 0.01 for ALT and eta (2) = 0.052, p = 0.025 for AST). This
      observational study showed that the variant OCT1-Met420del may be more effective
      on plasma glucose than HbA1c. The variable response could account for a
      significant proportion of the variance in HbA1c levels observed following
      treatment with metformin. Metformin shows a significantly greater effect on ALT
      and AST in responders than in non-responders.

PMID- 24740686
TI  - Correlations in distribution and concentration of calcium, copper and iron with
      zinc in isolated extracellular deposits associated with age-related macular
      degeneration.
AB  - Zinc (Zn) is abundantly enriched in sub-retinal pigment epithelial (RPE)
      deposits, the hallmarks of age-related macular degeneration (AMD), and is thought
      to play a role in the formation of these deposits. However, it is not known
      whether Zn is the only metal relevant for sub-RPE deposit formation. Because of
      their involvement in the pathogenesis of AMD, we determined the concentration and
      distribution of calcium (Ca), iron (Fe) and copper (Cu) and compared these with
      Zn in isolated and sectioned macular (MSD), equatorial (PHD) and far peripheral
      (FPD) sub-RPE deposits from an 86 year old donor eye with post mortem diagnosis
      of early AMD. The sections were mounted on Zn free microscopy slides and analyzed
      by microprobe synchrotron X-ray fluorescence (MUSXRF). Metal concentrations were
      determined using spiked sectioned sheep brain matrix standards, prepared the same
      way as the samples. The heterogeneity of metal distributions was examined using
      pixel by pixel comparison. The orders of metal concentrations were Ca ? Zn > Fe
      in all three types of deposits but Cu levels were not distinguishable from
      background values. Zinc and Ca were consistently present in all deposits but
      reached highest concentration in MSD. Iron was present in some but not all
      deposits and was especially enriched in FPD. Correlation analysis indicated
      considerable variation in metal distribution within and between sub-RPE deposits.
      The results suggest that Zn and Ca are the most likely contributors to deposit
      formation especially in MSD, the characteristic risk factor for the development
      of AMD in the human eye. 

PMID- 24740687
TI  - Examining short-term nutritional status among BaAka foragers in transitional
      economies.
AB  - Foragers in transitioning economies are at an increased risk of negative health
      outcomes as they undergo changes in subsistence patterns and diet. Here, we
      provide anthropometric data and examine the nutrition and health of adult BaAka
      foragers in relationship to declining wildlife and economic change in the Dzanga
      Sangha Protected Areas (APDS), Central African Republic. From June to August
      2012, we collected biological data and dietary recall surveys from individuals in
      Mossapoula (MS) and Yandoumbe (YDBE) villages using standard anthropometric
      techniques and a single capillary blood finger prick. In our analysis, we
      identified variation in anthropometric measurements and hemoglobin levels by
      village (MS = 66, YDBE = 75) and gender (64 men, 77 women). Immigration,
      increased gun hunting and wildlife trades have reduced forager reliance on forest
      resources. These changes are evidenced in the marginal health of contemporary
      BaAka foragers of APDS. Although anthropometric measures of nutritional status do
      not significantly differ between communities, hemoglobin data highlight
      inequities in access to forest products between villages with different proximity
      to community hunting zones. Further, poor dietary diversity and low frequency of
      purchased foods in the diet indicate that the transition to a market economy has
      not been fully realized and diets are impoverished. Economic changes appear to
      have had the most impact at MS village, where forest use is most restricted and
      consumption of meat and forest products was reduced. This work highlights the
      nutritional and health needs of foragers in rapidly transitioning economies;
      especially those impacted by conservation management and zoning policies.

PMID- 24740688
TI  - The myosin-activated thin filament regulatory state, M--open: a link to
      hypertrophic cardiomyopathy (HCM).
AB  - This review proposes a link between the hypertrophic (HCM) and restrictive
      cardiomyopathies caused by mutations in several sarcomeric thin filament
      proteins, and the open state of the three-state muscle regulation theory. The
      three characteristics of various muscle systems reconstituted from HCM mutated
      proteins (increased Ca(2+)-sensitivity, increased basal activity in the absence
      of Ca(2+), and decreased cooperativity) can be explained by the contribution of a
      myosin-induced open state (M (-) ), which elevates the basal activity and
      competes with the normal Ca(2+)-activated pathway. A model based on the three
      state theory of regulation, shows how a change in the closed/blocked equilibrium
      caused by a mutation that weakens the binding of troponin I to tropomyosin-actin
      can produce the characteristics of HCM. This review also shows that in the M (-)
      state, Ca(2+) can shift the closed-open equilibrium of the N-terminal hydrophobic
      region of troponin C without affecting activity. 

PMID- 24740689
TI  - A web-based restriction endonuclease tool for mycobacteriophage cluster
      prediction.
AB  - A recent explosion in the amount of genomic data has revealed a large genetic
      diversity in the bacteriophages that infect Mycobacterium smegmatis. In an effort
      to assess the novelty of newly described mycobacteriophage isolates and provide a
      preliminary determination of their probable cluster assignment prior to full
      genome sequencing, we have developed a systematic approach that relies on
      restriction endonuclease analysis. We demonstrate that a web-based tool, the
      Phage Enzyme Tool (or PET), is capable of rapidly facilitating this analysis and
      exhibits reliability in the putative placement of mycobacteriophages into
      specific clusters of previously sequenced phages. We propose that this tool
      represents a useful analytical step in the initial study of phage genomes and
      that this tool will increase the efficiency of phage genome characterization and
      enhance the educational activities involving mycobacteriophage discovery.

PMID- 24740690
TI  - Human acetyl-CoA carboxylase 2 expressed in silkworm Bombyx mori exhibits
      posttranslational biotinylation and phosphorylation.
AB  - Biotin-dependent human acetyl-CoA carboxylases (ACCs) are integral in homeostatic
      lipid metabolism. By securing posttranslational biotinylation, ACCs perform
      coordinated catalytic functions allosterically regulated by
      phosphorylation/dephosphorylation and citrate. The production of authentic
      recombinant ACCs is heeded to provide a reliable tool for molecular studies and
      drug discovery. Here, we examined whether the human ACC2 (hACC2), an isoform of
      ACC produced using the silkworm BmNPV bacmid system, is equipped with proper
      posttranslational modifications to carry out catalytic functions as the silkworm
      harbors an inherent posttranslational modification machinery. Purified hACC2
      possessed genuine biotinylation capacity probed by biotin-specific streptavidin
      and biotin antibodies. In addition, phosphorylated hACC2 displayed limited
      catalytic activity whereas dephosphorylated hACC2 revealed an enhanced enzymatic
      activity. Moreover, hACC2 polymerization, analyzed by native page gel analysis
      and atomic force microscopy imaging, was allosterically regulated by citrate and
      the phosphorylation/dephosphorylation modulated citrate-induced hACC2
      polymerization process. Thus, the silkworm BmNPV bacmid system provides a
      reliable eukaryotic protein production platform for structural and functional
      analysis and therapeutic drug discovery applications implementing suitable
      posttranslational biotinylation and phosphorylation. 

PMID- 24740691
TI  - Phosphoketolases from Lactococcus lactis, Leuconostoc mesenteroides and
      Pseudomonas aeruginosa: dissimilar sequences, similar substrates but distinct
      enzymatic characteristics.
AB  - Phosphoketolases (PKs) are large thiamine pyrophosphate (TPP)-dependent enzymes
      playing key roles in a number of essential pathways of carbohydrate metabolism.
      The putative PK genes of Lactococcus lactis (Ll) and Leuconostoc mesenteroides
      (Lm) were cloned in a prokaryotic vector, and the encoded proteins were expressed
      and purified yielding high purity proteins termed PK-Ll and PK-Lm, respectively.
      Similarly, the PK gene of Pseudomonas aeruginosa was expressed, and the
      corresponding protein (PK-Pa) was purified to homogeneity. The amino acid
      sequences predicted on the basis of genes' nucleotide sequences were confirmed by
      mass spectrometry and display low relative similarities. Circular dichroism (CD)
      spectra of these proteins predict higher alpha-helix than beta-strand contents.
      In addition, it is predicted that PK-Ll contains tightly packed domains.
      Enzymatic analysis showed that all three recombinant proteins, despite their
      dissimilar amino acid sequences, are active PKs and accept both xylulose 5
      phosphate (X5P) and fructose 6-phosphate (F6P) as substrates. However, they
      display substantially higher preference for X5P than for F6P. Kinetic
      measurements indicated that PK-Pa has the lowest Km values for X5P and F6P
      suggesting the highest capacity for substrate binding. PK-Ll has the largest kcat
      values for both substrates. Nevertheless, in terms of substrate specificity
      constant, PK-Pa has been found to be the most active PK against X5P. Structural
      models for all three analysed PKs predict similar folds in spite of amino acid
      sequence dissimilarities and contribute to understanding the enzymatic
      peculiarities of PK-Pa compared to PK-Ll and PK-Lm.

PMID- 24740692
TI  - Skin testing and patch testing in non-IgE-mediated drug allergy.
AB  - Drug skin tests can reproduce delayed hypersensitivity to drugs and entail a
      moderate reexposure of patients to offending drugs. Drug patch tests (DPTs) and
      prick tests can be done with any commercialized form of a drug. In non-severe
      delayed non-IgE-mediated reactions to drugs, intradermal tests (IDT) with delayed
      readings have a greater value, but their techniques lack standardization. A
      negative drug skin test does not exclude the responsibility of a drug, and the
      drug must be rechallenged in non-severe cases. DPTs are useful in maculopapular
      rashes, flexural exanthemas, and if done in situ, also in fixed drug eruption.
      Their best indication is in acute generalized exanthematous pustulosis or drug
      reaction with eosinophilia and systemic symptoms (DRESS). They should be carried
      out cautiously, following strict guidelines. Prick tests have a low value but
      they can sometimes be positive on delayed readings. In non-severe delayed
      reactions to drugs, intradermal tests with delayed readings are the most
      sensitive skin tests especially for beta-lactam antibiotics, radiocontrast media,
      heparins but also some biological agents. The value of patch testing varies
      according to the implicated drug and the non-immediate adverse drug reaction. In
      DRESS, DPTs have a good value in testing carbamazepine or proton pump inhibitors
      but remain negative in testing with allopurinol or salazopyrin. In toxic
      epidermal necrolysis, DPTs are safe but positive in only 9 to 23 % of the
      reported cases. 

PMID- 24740693
TI  - Whole blood thrombin generation in Bmal1-deficient mice.
AB  - The Calibrated Automated Thrombogram (CAT) assay that measures thrombin
      generation (TG) in platelet-poor and -rich plasma, is increasingly being
      recognised as a more sensitive tool to determine the overall function of the
      haemostatic system. We developed a method enabling the measurement of TG in a
      small aliquot of blood. The objective was to validate this assay in mouse blood
      and to examine the rate and extent of TG in a mouse model of premature aging. TG
      was assayed in blood from 20- to 28-week-old brain and muscle ARNT-like protein-1
      (Bmal1)-deficient (knockout, KO) mice and wild-type (WT) littermates. Bmal1-KO
      mice are known to display symptoms of premature aging. TG was initiated by adding
      calcium, tissue factor and a thrombin specific substrate. After TG, the samples
      were prepared for scanning electron microscopy (SEM). The intra-assay variations
      (%) in mouse blood of the endogenous thrombin potential (ETP), peak height, lag
      time, time-to-peak and velocity index were 10% or less (n=24). We found that
      Bmal1-KO mice have a significantly (p<0.001) higher ETP (437 +/- 7 nM.min; mean
      +/- SD, n=7) when compared with WT mice (ETP=220 +/- 45 nM.min; mean +/- SD,
      n=5). The peak heights also differed significantly (p=0.027). By applying SEM we
      found that Bmal1 deficient mice display a denser fibrin network with smaller
      pores compared to WT mice. In conclusion, the whole blood TG assay in mice
      revealed to be reproducible. As a proof-of-principle we have shown that the whole
      blood TG assay is capable of detecting a prothrombotic phenotype in Bmal1-KO
      mice. 

PMID- 24740694
TI  - Long-range effects in anion-pi interactions: their crucial role in the inhibition
      mechanism of Mycobacterium tuberculosis malate synthase.
AB  - The glyoxylate shunt is an anaplerotic bypass of the traditional Krebs cycle. It
      plays a prominent role in Mycobacterium tuberculosis virulence, so it can be
      exploited for the development of antitubercular therapeutics. The shunt involves
      two enzymes: isocitrate lyase (ICL) and malate synthase (GlcB). The shunt
      bypasses two steps of the tricarboxylic acid cycle, allowing the incorporation of
      carbon, and thus, refilling oxaloacetate under carbon-limiting conditions. The
      targeting of ICL is complicated; however, GlcB, which accommodates the
      pantothenate tail of acetyl-CoA in the active site, is easier to target. A
      catalytic Mg(2+) unit is located at the bottom of the cavity, and plays a very
      important role. Recently, the development of effective antituberculosis drugs
      based on phenyldiketo acids (PDKAs) has been reported. Interestingly, all the
      crystal structures of GlcB-inhibitor complexes exhibit close contact between the
      carboxylate of Asp633 and the face of the aromatic ring of the inhibitor.
      Remarkably, the replacement of the phenyl ring in PDKA by aliphatic moieties
      yields inactive inhibitors, suggesting that the aromatic moiety is crucial for
      inhibition. However, the aromatic ring of PDKA is not electron-deficient, and
      consequently, the anion-pi interaction is expected to be very weak (dominated
      only by polarization effects). Herein, through a combination analysis of the
      recent X-ray structures of GlcB-PDKA complexes retrieved from the protein data
      bank (PDB) and computational ab initio studies (RI-MP2/def2-TZVP level of
      theory), we demonstrate the prominent role of the Mg(2+) ion in the active site,
      which promotes long-range enhancement of the anion-pi interaction. 

PMID- 24740696
TI  - Disentangling posterror and postconflict reduction of interference.
AB  - Conflict monitoring theory (CMT; Botvinick, Braver, Barch, Carter, & Cohen
      Psychological Review, 108, 624-652, 2001) states that response conflict, the
      simultaneous activation of two competing responses, increases task focus and
      reduces interference from irrelevant information. CMT also defines errors as
      conflict, and reduced interference effects have consistently been reported
      following errors (Ridderinkhof Psychological Research, 66, 312-323, 2002).
      However, previous computations of this posterror reduction of interference (PERI)
      have overlooked the congruency of the previous trial. This is problematic,
      because most errors are made on incongruent trials, creating a confound between
      (previous) accuracy and (previous) congruency. Therefore, it is likely that
      reduced interference following errors is in fact the congruency sequence effect
      (i.e., reduced interference following incongruent, relative to congruent,
      trials). Our results corroborate this idea by demonstrating that participants
      indeed showed significant PERI following a congruent trial, but inverse PERI
      following an incongruent trial. These findings are discussed in light of the
      adaptation-by-binding account (Verguts & Notebaert Psychological Review, 115, 518
      525, 2008, Trends in Cognitive Sciences, 13, 252-257, 2009). 

PMID- 24740695
TI  - Purification and characterization of novel cationic peroxidases from Asparagus
      acutifolius L. with biotechnological applications.
AB  - Four novel basic peroxidases, named AaP-1, AaP-2, AaP-3, and AaP-4, were purified
      from Asparagus acutifolius L. seeds by cation-exchange and gel filtration
      chromatographies. The four proteins showed a similar electrophoretic mobility of
      46 kDa while, by MALDI-TOF MS, different Mr values of 42758.3, 41586.9, 42796.3,
      and 41595.5 were determined for AaP-1, AaP-2, AaP-3, and AaP-4, respectively. N
      terminal sequences of AaPs 1-4 up to residue 20 showed a high percentage of
      identity with the peroxidase from Glycine max. In addition, AaP-1, AaP-2, AaP-3,
      and AaP-4 were found to be glycoproteins, containing 21.75, 22.27, 25.62, and
      18.31 % of carbohydrates, respectively. Peptide mapping and MALDI-TOF MS analysis
      of AaPs 1-4 showed that the structural differences between AaP-1 and AaP-2 and
      AaP-3 and AaPs-4 were mainly due to their glycan content. We also demonstrate
      that AaPs were able to remove phenolic compounds from olive oil mill wastewaters
      with a higher catalytic efficiency with respect to horseradish peroxidase, thus
      representing candidate enzymes for potential biotechnological applications in the
      environmental field.

PMID- 24740697
TI  - CO/C-H as an acylating reagent: a palladium-catalyzed aerobic oxidative
      carbonylative esterification of alcohols.
AB  - A palladium-catalyzed oxidative carbonylative esterification of a variety of
      functionalized alcohols under base- and ligand-free conditions has been
      demonstrated. A CO/olefin combination was utilized as the acylating reagent with
      O2 as a benign oxidant. Notably, the scope of the substrate alcohols has been
      greatly broadened. 

PMID- 24740698
TI  - Neutrophil extracellular traps promote differentiation and function of
      fibroblasts.
AB  - Neutrophil activation by inflammatory stimuli and the release of extracellular
      chromatin structures (neutrophil extracellular traps - NETs) have been implicated
      in inflammatory disorders. Herein, we demonstrate that NETs released by
      neutrophils treated either with fibrosis-related agents, such as cigarette smoke,
      magnesium silicate, bleomycin, or with generic NET inducers, such as phorbol 12
      myristate 13-acetate, induced activation of lung fibroblasts (LFs) and
      differentiation into myofibroblast (MF) phenotype. Interestingly, the
      aforementioned agents or IL-17 (a primary initiator of inflammation/fibrosis) had
      no direct effect on LF activation and differentiation. MFs treated with NETs
      demonstrated increased connective tissue growth factor expression, collagen
      production, and proliferation/migration. These fibrotic effects were
      significantly decreased after degradation of NETs with DNase1, heparin or
      myeloperoxidase inhibitor, indicating the key role of NET-derived components in
      LF differentiation and function. Furthermore, IL-17 was expressed in NETs and
      promoted the fibrotic activity of differentiated LFs but not their
      differentiation, suggesting that priming by DNA and histones is essential for IL
      17-driven fibrosis. Additionally, autophagy was identified as the orchestrator of
      NET formation, as shown by inhibition studies using bafilomycin A1 or wortmannin.
      The above findings were further supported by the detection of NETs in close
      proximity to alpha-smooth muscle actin (alpha-SMA)-expressing fibroblasts in
      biopsies from patients with fibrotic interstitial lung disease or from skin scar
      tissue. Together, these data suggest that both autophagy and NETs are involved
      not only in inflammation but also in the ensuing fibrosis and thus may represent
      potential therapeutic targets in human fibrotic diseases.

PMID- 24740699
TI  - Displaced inferior ramus fractures as a marker of posterior pelvic injury.
AB  - INTRODUCTION: Injuries to the anterior or posterior pelvic ring rarely occur in
      isolation. Disruption to the anterior pelvic ring, indicated by a fracture of the
      superior or inferior pubic ramus, or injury to the pubic symphysis, may be
      indicative of additional pelvic ring disruption. The purpose of this
      retrospective study was to determine whether displaced inferior pubic ramus
      fractures warrant a more detailed investigation of the posterior ring in an
      effort to predict unstable posterior pelvic ring injuries. MATERIALS AND METHODS:
      All patients with a displaced inferior ramus fracture on AP pelvic radiograph
      were identified at a single level I trauma center over a 5-year period. Complete
      pelvic radiographs and computed tomography scans were then evaluated for
      additional pelvic ring injuries. The data were analyzed using the chi-square test
      to determine the association between inferior ramus fractures and posterior
      pelvic ring injury. RESULTS: Sixty-three of the 93 patients with a fracture of
      the inferior ramus (68 %) were found to have a posterior ring injury; 60 % of
      these injuries were unstable. Patients with concurrent superior ramus fractures
      were more likely to have a posterior ring injury (p < 0.001) and an unstable
      pelvis (p = 0.018). Of those with a displaced unilateral inferior ramus fracture,
      parasymphyseal involvement was associated with higher incidence of posterior ring
      injury (p = 0.047) and pelvic instability (p = 0.028). CONCLUSION: The anterior
      pelvic ring can be used to help identify unstable injuries to the posterior
      pelvis. Patients with displaced inferior pubic ramus fractures warrant a detailed
      examination of their posterior ring to identify additional injuries and
      instability.

PMID- 24740700
TI  - The clinical impact of using p16(INK4a) immunochemistry in cervical
      histopathology and cytology: an update of recent developments.
AB  - Cervical cancer screening test performance has been hampered by either lack of
      sensitivity of Pap cytology or lack of specificity of Human Papillomavirus (HPV)
      testing. This uncertainty can lead to unnecessary referral and treatment, which
      is disturbing for patients and increases costs for health care providers. The
      identification of p16(INK4a) as a marker for neoplastic transformation of
      cervical squamous epithelial cells by HPVs allows the identification of HPV
      transformed cells in histopathology or cytopathology specimens. Diagnostic
      studies have demonstrated that the use of p16(INK4a) immunohistochemistry
      substantially improves the reproducibility and diagnostic accuracy of
      histopathologic diagnoses. p16(INK4a) cytology has substantially higher
      sensitivity for detection of cervical precancer in comparison to conventional Pap
      tests. Compared to HPV DNA tests, immunochemical detection of p16(INK4a) -stained
      cells demonstrates a significantly improved specificity with remarkably good
      sensitivity. About 15 years after the initial observation that p16(INK4a) is
      overexpressed in HPV-transformed cells we review the accumulated clinical
      evidence suggesting that p16(INK4a) can serve as a useful biomarker in the
      routine diagnostic work up of patients with HPV infections and associated lesions
      of the female anogenital tract. 

PMID- 24740701
TI  - A self-oscillating gel actuator driven by ferroin.
AB  - In the wake of the Belousov-Zhabotinsky reaction catalyzed by ferroin, the
      swelling-deswelling oscillating soft actuator exhibits 7 min period of self
      oscillation for the first time. 

PMID- 24740704
TI  - Uncertainty in management of carotid stenosis in women.

PMID- 24740703
TI  - Reappraisal of central pancreatectomy a 12-year single-center experience.
AB  - IMPORTANCE: Central pancreatectomy, as an alternative to standard resection for
      benign and low-grade pancreatic neoplasms, has been described in mainly small
      retrospective series. OBJECTIVE: To describe a large single-center experience
      with central pancreatectomy. DESIGN, SETTING, AND PARTICIPANTS: A retrospective
      case series in a tertiary referral center included 100 consecutive patients
      undergoing central pancreatectomy with pancreaticogastrostomy from January 1,
      2000, to March 1, 2012. MAIN OUTCOMES AND MEASURES: Surgical indications,
      postoperative morbidity, mortality, and long-term outcomes regarding pancreatic
      function and recurrence. RESULTS: Central pancreatectomies were performed mainly
      for neuroendocrine tumors (35%), intraductal papillary mucinous neoplasms (33%),
      solid pseudopapillary neoplasms(12%), and mucinous cystadenomas (6%). The
      postoperative mortality rate was 3% (due to pulmonary embolisms in 2 patients and
      hemorrhage after pancreatic fistula in 1 patient). Clavien-Dindo III or IV
      complications occurred in 15%of patients and were due mainly to pancreatic
      fistula, requiring 10 radiologic drainage procedures, 7 endoscopic procedures,
      and 6 reoperations overall. After a median follow-up of 36 months, the rates of
      new-onset exocrine and endocrine insufficiency were 6%and 2%, respectively.
      Overall, 7 lesions could be considered undertreated, including 3 node-negative R0
      microinvasive intraductal papillary mucinous neoplasms (without recurrence at 27,
      29, and 34 months) and 4 node-positive neuroendocrine tumors (with 1 hepatic
      recurrence at 66 months). Among the 25 patients with a doubtful preoperative
      diagnosis, 9 could be considered over treated (ie, operated on for benign non
      evolutive asymptomatic lesions). CONCLUSIONS AND RELEVANCE: Central
      pancreatectomy is associated with an excellent pancreatic function at the expense
      of a significant morbidity and a non-nil mortality rate,underestimated by the
      published literature. The procedure is best indicated for benign or low-grade
      lesions in young and fit patients who can sustain a significant postoperative
      morbidity and could benefit from the excellent long-term results.

PMID- 24740705
TI  - Uncertainty in management of carotid stenosis in women-reply.

PMID- 24740707
TI  - Intersectional inequalities in immunization in India, 1992-93 to 2005-06: a
      progress assessment.
AB  - Immunization in India is marked with stark disparities across gender, caste,
      wealth and place of residence with severe shortfalls among those disadvantaged in
      more than one dimension. In this regard, an explicit recognition of
      intersectionality and intersectional inequalities has 2-fold relevance; one,
      being the pathway of health inequality and the other being its role as a
      deterrent of progress particularly at higher (better) levels of health. Against
      this backdrop, this study examines intersectional inequalities in immunization in
      India and also suggests a level-sensitive progress assessment method. The study
      uses group analogue of Gini coefficient for highlighting the magnitude of
      intersectional inequality and for comprehending its association with immunization
      level. The results unravel the plight of vulnerable intersectional groups and
      draw attention to disquieting shortfalls among female SCST (scheduled castes and
      tribes) children from rural areas. There is also some evidence to indicate
      leveraging among rural males in matters of immunization and it is further
      discerned that such gender advantage is greater among rural non-SCST community
      than the rural SCST group. In concluding, the study calls for intensive
      immunization planning to improve coverage among vulnerable communities in both
      rural and urban areas. 

PMID- 24740708
TI  - Priority setting in HIV/AIDS control in West Java Indonesia: an evaluation based
      on the accountability for reasonableness framework.
AB  - BACKGROUND: Indonesia has insufficient resources to adequately respond to the
      HIV/AIDS epidemic, and thus faces a great challenge in prioritizing
      interventions. In many countries, such priority setting processes are typically
      ad hoc and not transparent leading to unfair decisions. Here, we evaluated the
      priority setting process in HIV/AIDS control in West Java province against the
      four conditions of the accountability for reasonableness (A4R) framework:
      relevance, publicity, appeals and revision, and enforcement. METHODS: We reviewed
      government documents and conducted semi-structured qualitative interviews based
      on the A4R framework with 22 participants of the 5-year HIV/AIDS strategy
      development for 2008-13 (West Java province) and 2007-11 (Bandung). RESULTS: We
      found that criteria for priority setting were used implicitly and that the
      strategies included a wide range of programmes. Many stakeholders were involved
      in the process but their contribution could be improved and particularly the
      public and people living with HIV/AIDS could be better engaged. The use of appeal
      and publicity mechanisms could be more transparent and formally stated. Public
      regulations are not yet installed to ensure fair priority setting. CONCLUSIONS:
      To increase fairness in HIV/AIDS priority setting, West Java should make
      improvements on all four conditions of the A4R framework.

PMID- 24740709
TI  - Does human resource management improve family planning service quality? Analysis
      from the Kenya Service Provision Assessment 2010.
AB  - INTRODUCTION: Human resource (HR) management is a priority for health systems
      strengthening in developing countries, yet few studies have empirically examined
      associations with service quality. The purpose of this study was to assess the
      relationship between HR management and family planning (FP) service quality.
      METHODS: Data came from the 2010 Kenya Service Provision Assessment, a nationally
      representative health facility assessment. In total, 912 FP consultations from
      301 facilities were analysed. Four indices were created to measure quality on
      reproductive history taking, physical examination, sexually transmitted
      infections prevention and pill/injectable specific counselling. HR management
      variables included training in the past year, any and supportive (i.e. with
      feedback, technical updates and discussion) in-person supervision in the past 6
      months and having a written job description. Multivariate linear regression
      analyses were conducted to estimate coefficients of HR management variables on
      each of the four quality indices, adjusting for background characteristics of
      clients, provider and facilities. RESULTS: The level of service quality ranged
      from 16 to 53 out of a maximum score of 100 across the indices. Fifty-two per
      cent of consultations were done by providers who received supportive in-person
      supervision in the previous 6 months. In 23% and 38% of consultations, the
      provider was trained in the past year and had a written job description,
      respectively. Multivariate analyses indicated that having a written job
      description was associated with higher service quality in history taking,
      physical examination and the pill/injectable specific counselling. Other HR
      management variables were not significantly associated with service quality.
      CONCLUSION: Having a written job description was significantly associated with
      higher service quality and may be a useful tool for strengthening management
      practices. The details of such job descriptions and the quality of other
      management indicators should be explored to better understand the relationship
      between HR management and FP service quality.

PMID- 24740710
TI  - Health policy evolution in Lao People's Democratic Republic: context, processes
      and agency.
AB  - During the last 20 years Lao People's Democratic Republic has successfully
      developed and adopted some 30 health policies, strategies, decrees and laws in
      the field of health. Still, the implementation process remains arduous. This
      article aims at discussing challenges of health policy development and effective
      implementation by contextualizing the policy evolution over time and by focusing
      particularly on the National Drug Policy and the Health Care Law. Special
      attention is given to the role of research in policymaking. The analysis was
      guided by the conceptual framework of policy context, process, content and
      actors, combined with an institutional perspective, and showed that effective
      implementation of a health policy is highly dependent on both structures and
      agency of those involved in the policy process. The National Drug Policy was
      formulated and adopted in a short period of time in a resource-scarce setting,
      but with dedicated policy entrepreneurs and support of concerned international
      collaborators. Timely introduction of operational health systems research played
      a crucial role to support the implementation, as well as the subsequent revision
      of the policy. The development of the Health Care Law took several years and once
      adopted, the implementation was delayed by institutional legacies and issues
      concerning the choice of institutional design and financing, despite strong
      support of the law among the policymakers. Among many factors, timing of the
      implementation appeared to be of crucial importance, in combination with strong
      leadership. These two examples show that more research, that problematizes the
      complex policy environment in combination with improved communication between
      researchers and policymakers, is necessary to inform about measures for effective
      implementation. A way forward can be to strengthen the domestic research capacity
      and the international research collaboration regionally as well as globally. 

PMID- 24740711
TI  - Elective versus deferred stenting following subintimal recanalization of coronary
      chronic total occlusions.
AB  - Subintimal tracking and re-entry (STAR) technique has been described as a bailout
      strategy for coronary total occlusion (CTO) recanalization. However, the length
      of the dissected segment represents a major concern. The aim of this study is, to
      evaluate whether "deferred" stent implantation may limit the total stent length
      following STAR recanalization of CTO. All consecutive patients with CTO in a
      native coronary artery treated by successful STAR technique in our institution
      were included. In the first period (March 2004-December 2009) all procedures were
      completed with stent implantation (Elective Stent Group; n = 60). Thereafter
      (January 2010-June 2012) stent implantation was postponed until a scheduled
      (within 3 months) angiographic follow-up (Deferred Stent Group; n = 69). The
      dissection length was 75 +/- 37 mm in the Elective Stent Group and 83 +/- 31 mm
      in the Deferred Stent Group (P = 0.22). In the Deferred Stent Group, at the
      angiographic follow-up, the dissection length was significantly shorter than at
      the index procedure (40 +/- 35 mm versus 83 +/- 31 mm, P <0.001). The total stent
      length was significantly shorter in the Deferred Stent Group versus the Elective
      Stent Group (22 +/- 33 mm versus 56 +/- 28 mm; P < 0.001). At six-month follow
      up, rate of cardiac death and myocardial infarction (6.7% vs 0; P = 0.049) and of
      stent thrombosis (5% vs 0%; P = 0.10) were higher in the Elective Stent Group.
      The present study suggests that deferring stenting implantation following STAR
      recanalization (1) limits the stent length and (2) is associated with a lower
      rate of objective endpoints.

PMID- 24740712
TI  - Cell-penetrable lysine dendrimers for anti-cancer drug delivery: synthesis and
      preliminary biological evaluation.
AB  - Improving the cell penetration and enhancing the cell selectivity of drugs have
      been approved for overcoming the major drawbacks of chemotherapeutic agents: the
      toxicity to normal cells and the drug resistance in tumors. In this paper, lysine
      dendrimers (G1-G3) were chosen as novel cell-penetrating carriers for anti-cancer
      drugs based on the internalization mechanism of cell-penetrating peptides and the
      characteristics of dendritic peptides. After labeling with fluorescein
      isothiocyanate (FITC), the cell-penetrable capacity of lysine dendrimers was
      certified by flow cytometric analysis. In a preliminary biological evaluation,
      the conjugates of lysine dendrimers and 5-fluorouracil showed the expected
      advantages: stable drug release, low toxicity to normal cells, and moderate
      inhibition of tumor cells. These results imply that cell-penetrable lysine
      dendrimers could be potential carriers in drug delivery of anti-cancer medicine.

PMID- 24740713
TI  - Effect of lowering or restricting sympathectomy levels on compensatory sweating.
AB  - OBJECTIVE: There is controversy on whether lowering or restricting the level of
      sympathectomy can reduce compensatory sweating (CS). This study compared the
      results from sympathectomies performed to treat severe palmar hyperhidrosis using
      two distinct levels of T2-4 and T3-4. METHODS: One hundred and sixteen patients
      with primary palmar hyperhidrosis were randomly allocated to undergo either T2-4
      sympathectomy treatment (T2-4 group) or T3-4 sympathectomy treatment (T3-4
      group). Follow-up data were collected using a telephone questionnaire to assess
      efficacy, side effects, overall satisfaction, and factors affecting CS and the
      degree of satisfaction. RESULTS: There were no significant differences with
      respect to either CS or severe CS between the two treatment groups at 1, 6, or 12
      months of follow-up. The total scores of the quality-of-life questionnaires after
      surgery were remarkably decreased compared with those before surgery in the two
      groups. However, no significant differences in quality-of-life scores were found
      between the two groups before surgery, or at 1, 6, or 12 months of follow-up. Age
      was predictive of severe CS at 6 months of follow-up (P = 0.045). Severe CS was
      inversely associated with patient satisfaction at 1, 6, and 12 months of follow
      up. INTERPRETATION: The issue of whether lowering or restricting the level of
      sympathectomy reduces CS is controversial and needs more supportive evidence. Age
      may be a predictive factor for severe CS at 6 and 12 months of follow-up. Severe
      CS is the only known factor that affects patient satisfaction, and family history
      may also be associated with patient satisfaction.

PMID- 24740714
TI  - Molecular dynamics simulations demonstrate the regulation of DNA-DNA attraction
      by H4 histone tail acetylations and mutations.
AB  - The positively charged N-terminal histone tails play a crucial role in chromatin
      compaction and are important modulators of DNA transcription, recombination, and
      repair. The detailed mechanism of the interaction of histone tails with DNA
      remains elusive. To model the unspecific interaction of histone tails with DNA,
      all-atom molecular dynamics (MD) simulations were carried out for systems of four
      DNA 22-mers in the presence of 20 or 16 short fragments of the H4 histone tail
      (variations of the 16-23 a. a. KRHRKVLR sequence, as well as the unmodified
      fragment a. a.13-20, GGAKRHRK). This setup with high DNA concentration, explicit
      presence of DNA-DNA contacts, presence of unstructured cationic peptides (histone
      tails) and K(+) mimics the conditions of eukaryotic chromatin. A detailed account
      of the DNA interactions with the histone tail fragments, K(+) and water is
      presented. Furthermore, DNA structure and dynamics and its interplay with the
      histone tail fragments binding are analysed. The charged side chains of the
      lysines and arginines play major roles in the tail-mediated DNA-DNA attraction by
      forming bridges and by coordinating to the phosphate groups and to the
      electronegative sites in the minor groove. Binding of all species to DNA is
      dynamic. The structure of the unmodified fully-charged H4 16-23 a.a. fragment
      KRHRKVLR is dominated by a stretched conformation. The H4 tail a. a. fragment
      GGAKRHRK as well as the H4 Lys16 acetylated fragment are highly flexible. The
      present work allows capturing typical features of the histone tail-counterion-DNA
      structure, interaction and dynamics.

PMID- 24740716
TI  - Polarization enhancement of microwave absorption by increasing aspect ratio of
      ellipsoidal nanorattles with Fe3O4 cores and hierarchical CuSiO3 shells.
AB  - The shape anisotropy of the nanostructured nanorattles is one of the key factors
      that affect their microwave absorption performance. In the present study, the
      microwave absorption performance of ellipsoidal Fe3O4@CuSiO3 nanorattles with
      different aspect ratios was investigated. Results demonstrated that the
      ellipsoidal nanorattles with the aspect ratio of 3-4 exhibited about 20%
      enhancement of microwave absorption intensity compared with spherical
      Fe3O4@CuSiO3. Generally, as the aspect ratio increased from 2.0 to 3.5, the
      microwave absorption peak was enhanced monotonously from -20 dB to -30 dB. It was
      found that the ellipsoidal nanorattles with larger aspect ratio exhibited higher
      coercivity and double resonance peaks of the real part of complex permittivity,
      resulting in the improvement of microwave absorption performance. Our research
      gives insights into the understanding of the anisotropic effect of nanorattles on
      microwave absorption performance. 

PMID- 24740715
TI  - Identification of effective Pb resistant bacteria isolated from Lens culinaris
      growing in lead contaminated soils.
AB  - Soil bacteria are a new phytoremediation system for the removal of heavy metals
      from soils. In this study, fifteen soil bacteria were isolated from root nodules
      of lentil growing in heavy metals contaminated soils, particularly by lead.
      Molecular characterization of the collection showed a large diversity, including
      Agrobacterium tumefaciens, Rahnella aquatilis, Pseudomonas, and Rhizobium sp.
      These soil bacteria had a wide range of tolerance to heavy metals. Among them,
      strains of A. tumefaciens and R. aquatilis tolerated up to 3.35 mM Pb; whereas
      Pseudomonas tolerated up to 3.24 mM Pb. The inoculation of lentil grown
      hydroponically with inoculums formed by these efficient and Pb resistant bacteria
      enhanced plant biomass. The treatment of this symbiosis by 1 mM Pb for 10 days or
      by 2 mM Pb for 3 days demonstrated that lentil had Pb accumulation capacity and
      can be considered a Pb accumulator plant, elsewhere, roots accumulated more Pb
      than shoots, and the inoculation decreased the Pb up take by the plants,
      suggesting that this symbiosis should be investigated for use in
      phytostabilization of Pb-contaminated soils. At the same time, a modulation in
      the antioxidant enzyme activity and a specific duration was required for the
      induction of the superoxide dismutase (SOD), peroxidase (POX), and ascorbate
      peroxidase (APX) response and to adapt to Pb stress. These results suggested that
      these enzymes may be involved in the main mechanism of antioxidative defense in
      lentil exposed to Pb oxidative stress. 

PMID- 24740717
TI  - Improvement in autologous human fat transplant survival with SVF plus VEGF-PLA
      nano-sustained release microspheres.
AB  - Early neovascularization is important for autologous fat transplant survival. SVF
      cells are ideal seed cells. Both vascular endothelial growth factor (VEGF) and
      SVF cells can promote neovascularization. However, the half-life (about 50 min)
      of VEGF is too short to sustain an adequate local concentration. We have
      investigated whether VEGF-polylactic acid (PLA) nano-sustained release
      microspheres plus SVF cells can improve neovascularization and survival of
      transplanted fat tissues. SVF cells were harvested and constructed VEGF-PLA nano
      sustained release microspheres in vitro. Human fat tissues was mixed with SVF
      cells plus VEGF-PLA, SVF cells alone or Dulbecco's modified Eagle's medium as the
      control. These three mixtures were injected into random sites in 18 nude mice.
      Two months later, the transplants were weighed and examined histologically; and
      capillaries were counted to quantify neovascularization. Hematoxylin-eosin (HE)
      and anti-VEGF stains were applied to reveal cell infiltration. The mean wet
      weight of fat in the SVF plus VEGF-PLA, SVF alone, and control transplants were
      0.18 +/- 0.013 g, 0.16 +/- 0.015 g, and 0.071 +/- 0.12 g, respectively; the
      differences between groups were statistically significant. More vessels were
      present in the SVF plus VEGF-PLA transplants than in the other two types.
      Transplants mixed with SVF cells also had an acceptable density of capillaries.
      Histological analysis revealed that both the SVF plus VEGF-PLA and SVF alone
      transplants, but not the control transplants, were composed of adipose tissue,
      and had less fat necrosis and less fibrosis than control specimens. SVF plus VEGF
      PLA transplants had significantly greater capillary density and VEGF expression
      than the other two transplant groups. Thus transplanted fat tissue survival and
      quality can be enhanced by the addition of VEGF-PLA nano-sustained release
      microspheres plus SVF cells.

PMID- 24740718
TI  - Maternal-child dyads of functioning: the intergenerational impact of violence
      against women on children.
AB  - Violence against women is a global epidemic with potential consequences of
      injury, illness, and death. Children exposed to the violence may also be impacted
      with functional impairments. Little is known of the inter-generational impact of
      violence experienced by the mother from an intimate partner on functioning of her
      children. No dyad analysis was found in the literature. To examine the inter
      generational impact of violence against women on the behavioral functioning of
      children, 300 mothers reporting intimate partner abuse and one randomly chosen
      child, age 18 months to 16 years of age; were evaluated for borderline and
      clinical diagnostic levels of problem behaviors. Linear, Logistic, and Ordinal
      regression models were applied. Mothers' problem behavior scores were
      significantly related to children's problem behavior scores (internalizing r =
      0.611, externalizing r = 0.494, total problems r = 0.662, all ps < 0.001).
      Mothers who reported clinical and borderline clinical internalized problems
      (i.e., depression, anxiety) were 7 times more likely to have children with the
      same problems and mothers with borderline clinical and clinical external problems
      (i.e., aggression, hostility) were 4.5 times more likely to have children with
      the same external problems. These dyadic analyses provide evidence of a direct
      relationship of maternal functioning on child behavioral functioning.
      Intervention strategies to decrease internalizing maternal behavioral problems,
      such as depression, anxiety, and post traumatic stress disorder, and/or
      externalizing problems, such as hostility and aggression, can be expected to have
      a pass through, secondary impact on the behavioral functioning of children.
      Awareness of the relationship between intimate partner violence against mothers
      and child behavioral function can support interventions that decrease the
      distress experienced by mothers and their children, interrupt intergenerational
      transmission of abusive behaviors, and promote better maternal child functioning.

PMID- 24740719
TI  - Impact of psychosocial risk factors on prenatal care delivery: a national
      provider survey.
AB  - To evaluate providers' perspectives regarding the delivery of prenatal care to
      women with psychosocial risk factors. A random, national sample of 2,095 prenatal
      care providers (853 obstetricians and gynecologists (Ob/Gyns), 270 family
      medicine (FM) physicians and 972 midwives) completed a mailed survey. We measured
      respondents' practice and referral patterns regarding six psychosocial risk
      factors: adolescence (age <=19), unstable housing, lack of paternal involvement
      and social support, late prenatal care (>13 weeks gestation), domestic violence
      and drug or alcohol use. Chi square and logistic regression analyses assessed the
      association between prenatal care provider characteristics and prenatal care
      utilization patterns. Approximately 60 % of Ob/Gyns, 48.4 % of midwives and 32.2
      % of FM physicians referred patients with psychosocial risk factors to clinicians
      outside of their practice. In all three specialties, providers were more likely
      to increase prenatal care visits with alternative clinicians (social workers,
      nurses, psychologists/psychiatrists) compared to themselves for all six
      psychosocial risk factors. Drug or alcohol use and intimate partner violence were
      the risk factors that most often prompted an increase in utilization. In
      multivariate analyses, Ob/Gyns who recently completed clinical training were
      significantly more likely to increase prenatal care utilization with either
      themselves (OR 2.15; 95 % CI 1.14-4.05) or an alternative clinician (2.27; 1.00
      4.67) for women with high psychosocial risk pregnancies. Prenatal care providers
      frequently involve alternative clinicians such as social workers, nurses and
      psychologists or psychiatrists in the delivery of prenatal care to women with
      psychosocial risk factors.

PMID- 24740720
TI  - Mode of childbirth in low-risk pregnancies: Nicaraguan physicians' viewpoints.
AB  - To explore attitudes of physicians attending births in the public and private
      sectors and at the managerial level toward cesarean birth in Nicaragua. A
      qualitative study was conducted consisting of four focus groups with 17
      physicians and nine in-depth interviews with decision-makers. Although study
      participants listed many advantages of vaginal birth and disadvantages of
      cesarean birth, they perceived that the increase in the cesarean birth rate in
      Nicaragua has resulted in a reduction in perinatal morbidity and mortality. They
      ascribed high cesarean birth rates to a web of interrelated provider, patient,
      and health system factors. They identified five actions that would facilitate a
      reduction in the number of unnecessary cesarean operations: establishing
      standards and protocols; preparing women and their families for labor and
      childbirth; incorporating cesarean birth rate monitoring and audit systems into
      quality assurance activities at the facility level; strengthening the movement to
      humanize birth; and promoting community-based interventions to educate women and
      families about the benefits of vaginal birth. Study participants believe that by
      performing cesarean operations they are providing the best quality of care
      feasible within their context. They do not perceive problems with their current
      practice. The identified causes of unnecessary cesarean operations in Nicaragua
      are multifactorial, so it appears that a multi-layered strategy is needed to
      safely reduce cesarean birth rates. The recent Nicaraguan Ministry of Health
      guidance to promote parto humanizado ("humanization of childbirth") could serve
      as the basis for a collaborative effort among health care professionals,
      government, and consumer advocates to reduce the number of unnecessary cesarean
      births in Nicaragua. 

PMID- 24740721
TI  - Engaging field-based professionals in a qualitative assessment of barriers and
      positive contributors to breastfeeding using the social ecological model.
AB  - Despite broad recognition of benefits associated with breastfeeding, rates in the
      United States continue to be below targets established by Healthy People 2020,
      especially for economically disadvantaged women. This study engaged field-based
      professionals through a focus group process to collect perceptions on factors
      that determine a woman's decision to breastfeed. Field-based professionals
      participated in one of six focus groups. Following the social ecological model
      (SEM), focus group questions addressed barriers and contributors to breastfeeding
      at the individual, interpersonal, community, organizational, and public policy
      levels. Thematic content analysis was used in identifying, analyzing, and
      reporting on themes within the focus group data. Commonly reported themes were
      identified that negatively influence a mother's decision to breastfeed such as
      modesty/general discomfort to breastfeed in front of others, negative
      breastfeeding perceptions of family members, friends, boyfriends and co-workers,
      breastfeeding not being viewed as the societal "norm", and the availability of
      free formula samples. Despite identified barriers, commonly reported themes that
      positively influence a mother's decision to breastfeed included general knowledge
      on the benefits, positive breastfeeding perceptions of family members, friends,
      boyfriends, and co-workers, the availability of "mom and baby" groups, and Baby
      Friendly hospital practices. The findings provide field-based perspectives that
      identify opportunities to support breastfeeding through the lens of the SEM.
      Opportunities to better support breastfeeding include educating mothers and their
      social support systems on the specific benefits of breastfeeding, challenging
      existing breastfeeding norms, and working with hospitals on establishing policy
      to not provide free formula samples. 

PMID- 24740722
TI  - Incidence of low birthweight in central Nepal: a community-based prospective
      cohort study.
AB  - Many deliveries in low income countries still take place at home and the newborns
      are often not weighed. This community-based study ascertained the incidence of
      low birthweight (LBW) and compared the birthweight between home- and facility
      born neonates in central Nepal. A total of 701 pregnant women from the Kaski
      district were recruited and interviewed. Birthweights of newborns were measured
      by pan balance in health facility settings immediately after birth, or by local
      community health volunteers using colour-coded spring balance within 48 h of home
      birth. Household follow up of participants were undertaken less than 45 days
      after delivery to record the weight of their infants. Of the 639 postpartum women
      who took part in the follow up interview, information on birthweight was
      available from 605 singleton births. Among them, 65 (10.7 %) were born at home.
      Overall, the mean birthweight was 3,059 (SD 464) g and incidence of LBW was 16.5
      % (95 % CI 13.5-19.5 %). However, the home-born infants reported significantly
      lower (p = 0.009) mean birthweight (2,920, SD 435 g) than their facility-born
      counterparts (3,078, SD 461 g). This difference in birthweight remained
      significant (p = 0.03) after adjustment for maternal and socio-demographic
      characteristics. Incidence of LBW in central Nepal was quite high. Home-born
      babies appeared to have lower birthweight and thus their inclusion could provide
      an accurate estimate of the LBW rate.

PMID- 24740723
TI  - Family process correlates of firearm ownership and firearm storage among families
      with young children.
AB  - To understand how family relations and dynamics were associated with firearm
      ownership among US families with 4-year-olds and with firearm storage among those
      families with firearms, controlling for sociodemographic characteristics of
      families and states. With representative data from the Early Childhood
      Longitudinal Study-Birth Cohort (n = 8,100), logistic regression models employed
      a set of family process variables (e.g., parenting practices, parental stress,
      maternal depression, and safety behaviors) as (1) predictors of firearm ownership
      among all families and, (2) as predictors of safe firearm storage among firearm
      owning families. An estimated 22 % of families with pre-kindergarten age children
      reported having firearms in their households. Among firearm owning families, 69 %
      of families kept firearms in a locked cabinet. Comparing families who did and did
      not report owning firearms, those who did were more likely to report spanking
      their children. Firearm owning parents who reported higher levels of parenting
      stress and lower likelihood that their child always wore a helmet when bicycling
      were also more likely to report unsafe firearm storage practices. Family
      processes differentiated both firearm owners from non-firearm owners and firearms
      owners who locked up their firearms from firearm owners who did not. These
      findings suggest that firearm ownership and firearm safety behaviors likely arise
      from a more general family context related to child health and safety.

PMID- 24740724
TI  - Lifestyle and dietary habits of an obese pregnant cohort.
AB  - Obese pregnant women are the focus of numerous dietary and lifestyle intervention
      studies, however there is a paucity of literature examining the habitual dietary
      and lifestyle habits of this population. This paper aims to assess maternal
      dietary and lifestyle habits in an obese cohort, in order to identify priority
      areas to be addressed in future studies and in clinical practice. This
      prospective observational study recruited 100 pregnant women with a body mass
      index 30.0-39.9 kg/m(2) from routine antenatal clinics. Dietary intakes were
      assessed using a 3-day food diary and a structured lifestyle questionnaire
      assessed physical activity levels, smoking and alcohol habits and wellbeing.
      Macronutrient intakes as a percentage of total energy were not compliant to
      healthy eating guidelines with an inadequate intake of carbohydrate and excess
      intake of saturated fat. Compliance to recommended intakes of calcium, iron,
      folate and vitamin D was poor from diet alone. The consumption of energy dense
      food groups high in fat and sugar was greater than for published pregnant
      populations and the general female non-pregnant population. One-third of women
      reported engaging in weekly physical activity that would comply with
      recommendations for pregnant women while 25 % reported low mood status indicating
      potential depression. High intakes of energy-dense processed foods and poor
      compliance to micronutrient recommendations are critical dietary issues of
      concern among obese pregnant women. Low mood is a barrier to motivation for
      changing behaviour which would also need to be addressed in future lifestyle
      intervention studies.

PMID- 24740725
TI  - Domestic violence among adolescents in HIV prevention research in Tanzania:
      participant experiences and measurement issues.
AB  - Under-representation of female adolescents in HIV clinical trials may inhibit
      their access to future prevention technologies. Domestic violence, broadly
      defined as violence perpetrated by intimate partners and/or family members, may
      affect trial participation. This study describes violence in the lives of
      adolescents and young women in Tanzania, explores use of the Women's Experience
      with Battering (WEB) Scale to measure battering, and examines the associations
      between battering and socio-demographic and HIV risk factors. Community formative
      research (CFR) and a mock clinical trial (MCT) were conducted to examine the
      challenges of recruiting younger (15-17) versus older (18-21) participants into
      HIV prevention trials. The CFR included qualitative interviews with 23
      participants and there were 135 MCT participants. The WEB was administered in
      both the CFR and MCT. Nineteen CFR participants experienced physical and/or
      sexual violence and 17 % scored positive for battering. All married participants
      reported partner-related domestic violence, and half scored positive for
      battering. Many believed beatings were normal. None of the single participants
      scored positive on battering, but one-third reported abuse by relatives. Among
      MCT participants, 15 % scored positive for battering; most perpetrators were
      relatives. Younger participants were more likely to report battering. Adolescents
      experienced high rates of domestic violence and the WEB captured battering from
      both partners and relatives. The level of familial violence was unexpected and
      has implications for parental roles in study recruitment. Addressing adolescent
      abuse in HIV prevention trials and in the general population should be a public
      health priority.

PMID- 24740727
TI  - State-of-the-art SPECT/CT: technology, methodology and applications-defining a
      new role for an undervalued multimodality imaging technique.

PMID- 24740726
TI  - Variation in child health care utilization by medical complexity.
AB  - Children with medical complexity (CMC) have multiple specialty need, technology
      dependence, and high health care utilization. The objective of this study is to
      profile types of pediatric health care utilization and costs by increasing levels
      of medical complexity. This is a cross-sectional study of the 2007, 2008 and 2009
      Full-Year Data Sets from the Medical Expenditure Panel Survey. Medical complexity
      was defined by a higher number of positive items from the five question children
      with special health care needs (CSHCN) Screener. CMC were defined by >= 4
      positive screener items. Outcomes included the number of inpatient, outpatient,
      and emergency department visits, associated costs and diagnoses, and reported
      satisfaction. ICD-9 codes were grouped by Clinical Classifications Software. Of
      27,755 total study subjects <= 17 years, 4,851 had special needs and 541 were
      CMC. Older age, male gender, white/non-Hispanic race/ethnicity, and public
      insurance were all associated with medical complexity (all p < 0.001). CMC had an
      annual mean of 19 annual outpatient visits ($616) and 0.26 inpatient visits
      ($3,308), with other significant cost drivers including home health ($2,957) and
      prescriptions ($2,182). The most common reasons for non-CSHCN and less-complex
      CSHCN outpatient visits were viral illnesses, while the main reasons for CMC
      visits were for mental health. Compared to families without CSHCN, those with CMC
      have, on average, lower satisfaction with health care (8.4 vs. 8.9 out of 10, p <
      0.001). Health care models for CMC should account for mental health conditions
      that may be driving high numbers of outpatient encounters.

PMID- 24740728
TI  - Transposed ovary mimicking a peritoneal implant on FDG PET/CT in a patient with
      carcinoma of the rectum.

PMID- 24740731
TI  - Hybrid nanocarbon as a catalyst for direct dehydrogenation of propane: formation
      of an active and selective core-shell sp2/sp3 nanocomposite structure.
AB  - Hybrid nanocarbon, comprised of a diamond core and a graphitic shell with a
      variable sp(2)-/sp(3)-carbon ratio, is controllably obtained through sequential
      annealing treatment (550-1300  degrees C) of nanodiamond. The formation of sp(2)
      carbon increases with annealing temperature and the nanodiamond surface is
      reconstructed from amorphous into a well-ordered, onion-like carbon structure via
      an intermediate composite structure--a diamond core covered by a defective,
      curved graphene outer shell. Direct dehydrogenation of propane shows that the
      sp(2)-/sp(3)-nanocomposite exhibits superior catalytic performance to that of
      individual nanodiamond and graphitic nanocarbon. The optimum catalytic activity
      of the diamond/graphene composite depends on the maximum structural defectiveness
      and high chemical reactivity of the ketone groups. Ketone-type functional groups
      anchored on the defects/vacancies are active for propene formation; nevertheless,
      once the oxygen functional groups are desorbed, the defects/vacancies alone might
      be active sites responsible for the C-H bond activation of propane.

PMID- 24740729
TI  - Lipotoxicity in the pancreatic beta cell: not just survival and function, but
      proliferation as well?
AB  - Free fatty acids (FFAs) exert both positive and negative effects on beta cell
      survival and insulin secretory function, depending on concentration, duration,
      and glucose abundance. Lipid signals are mediated not only through metabolic
      pathways, but also through cell surface and nuclear receptors. Toxicity is
      modulated by positive signals arising from circulating factors such as hormones,
      growth factors and incretins, as well as negative signals such as inflammatory
      mediators and cytokines. Intracellular mechanisms of lipotoxicity include
      metabolic interference and cellular stress responses such as oxidative stress,
      endoplasmic reticulum (ER) stress, and possibly autophagy. New findings
      strengthen an old hypothesis that lipids may also impair compensatory beta cell
      proliferation. Clinical observations continue to support a role for lipid biology
      in the risk and progression of both type 1 (T1D) and type 2 diabetes (T2D). This
      review summarizes recent work in this important, rapidly evolving field. 

PMID- 24740730
TI  - Organ repair, hemostasis, and in vivo bonding of medical devices by aqueous
      solutions of nanoparticles.
AB  - Sutures are traumatic to soft connective tissues, such as liver or lungs. Polymer
      tissue adhesives require complex in vivo control of polymerization or cross
      linking reactions and currently suffer from being toxic, weak, or inefficient
      within the wet conditions of the body. Herein, we demonstrate using Stober silica
      or iron oxide nanoparticles that nanobridging, that is, adhesion by aqueous
      nanoparticle solutions, can be used in vivo in rats to achieve rapid and strong
      closure and healing of deep wounds in skin and liver. Nanoparticles were also
      used to fix polymer membranes to tissues even in the presence of blood flow, such
      as occurring after liver resection, yielding permanent hemostasis within a
      minute. Furthermore, medical devices and tissue engineering constructs were fixed
      to organs such as a beating heart. The simplicity, rapidity, and robustness of
      nanobridging bode well for clinical applications, surgery, and regenerative
      medicine. 

PMID- 24740732
TI  - Design, characterization, and aerosol dispersion performance modeling of advanced
      co-spray dried antibiotics with mannitol as respirable
      microparticles/nanoparticles for targeted pulmonary delivery as dry powder
      inhalers.
AB  - Dry powder inhalation aerosols of antibiotic drugs (a first-line aminoglycoside,
      tobramycin, and a first-line macrolide, azithromycin) and a sugar alcohol
      mucolytic agent (mannitol) as co-spray dried (co-SD) particles at various molar
      ratios of drug:mannitol were successfully produced by organic solution advanced
      co-spray drying from dilute solute concentration. These
      microparticulate/nanoparticulate aerosols consisting of various antibiotic
      drug:mannitol molar ratios were rationally designed with a narrow and unimodal
      primary particle size distribution, spherical particle shape, relatively smooth
      particle surface, and very low residual water content to minimize the
      interparticulate interactions and enhance in vitro aerosolization. These
      microparticulate/nanoparticulate inhalation powders were high-performing aerosols
      as reflected in the aerosol dispersion performance parameters of emitted dose,
      fine particle fraction (FPF), respirable fraction (RF), and mass median
      aerodynamic diameter (MMAD). The glass transition temperature (Tg) values were
      significantly above room temperature, which indicated that the co-SD powders were
      all in the amorphous glassy state. The Tg values for co-SD tobramycin:mannitol
      powders were significantly lower than those for co-SD azithromycin:mannitol
      powders. The interplay between aerosol dispersion performance parameters and Tg
      was modeled where higher Tg values (i.e., more ordered glass) were correlated
      with higher values in FPF and RF and lower values in MMAD.

PMID- 24740733
TI  - Correlations between the clinical, histological and neurophysiological
      examinations in patients before and after parotid gland tumor surgery:
      verification of facial nerve transmission.
AB  - Parotid gland tumor surgery sometimes leads to facial nerve paralysis. Malignant
      more than benign tumors determine nerve function preoperatively, while
      postoperative observations based on clinical, histological and neurophysiological
      studies have not been reported in detail. The aims of this pilot study were
      evaluation and correlations of histological properties of tumor (its size and
      location) and clinical and neurophysiological assessment of facial nerve function
      pre- and post-operatively (1 and 6 months). Comparative studies included 17
      patients with benign (n = 13) and malignant (n = 4) tumors. Clinical assessment
      was based on House-Brackmann scale (H-B), neurophysiological diagnostics included
      facial electroneurography [ENG, compound muscle action potential (CMAP)], mimetic
      muscle electromyography (EMG) and blink-reflex examinations (BR). Mainly grade I
      of H-B was recorded both pre- (n = 13) and post-operatively (n = 12) in patients
      with small (1.5-2.4 cm) benign tumors located in superficial lobes. Patients with
      medium size (2.5-3.4 cm) malignant tumors in both lobes were scored at grade I (n
      = 2) and III (n = 2) pre- and mainly VI (n = 4) post-operatively. CMAP amplitudes
      after stimulation of mandibular marginal branch were reduced at about 25 % in
      patients with benign tumors after surgery. In the cases of malignant tumors CMAPs
      were not recorded following stimulation of any branch. A similar trend was found
      for BR results. H-B and ENG results revealed positive correlations between the
      type of tumor and surgery with facial nerve function. Neurophysiological studies
      detected clinically silent facial nerve neuropathy of mandibular marginal branch
      in postoperative period. Needle EMG, ENG and BR examinations allow for the
      evaluation of face muscles reinnervation and facial nerve regeneration.

PMID- 24740734
TI  - Results in using the Freiburger monosyllabic speech test in noise without and
      with hearing aids.
AB  - The Freiburger Speech Test (FST) has been the gold standard in speech testing by
      word recognition score in Germany for many years. Recently, it has been
      demonstrated that for an amount of 104 test-persons there is no significant
      deviation within the lists. The objective of this study was to determine the
      percentiles of the distinct measuring situations in quiet and with noise (e.g.
      applied in hearing aid fitting) and the average benefit using hearing aids. In
      this prospective study, 623 patients with SNHL and equipped with hearing aids for
      at least 3 months have been investigated by means of the Freiburger monosyllabic
      test (FBE) without and with hearing aids and in quiet or with noise (CCITT noise,
      65/60 dB signal-noise ratio) in free field conditions at 65 dB to determine the
      ratio of intelligibility. To investigate the different diagnostic conditions a
      linear mixed model was applied. The dependent binary variable corresponds to the
      number of understood syllables. The average age of all subjects was about 72.6
      years. The average rate of understanding in the FBE without hearing aids and in
      quiet was 38.5 %, with hearing aids and in quiet 67.7 %, without hearing aids and
      with noise 22.4 %, and with hearing aids and with noise 39.8 %. All results were
      presented with the depending confidence intervals. The extent of hearing loss and
      the quality of hearing aid fitting can be successfully measured using the FST in
      quiet and with background noise (CCITT noise). In quiet, an average hearing
      improving gain of 29.2 % points and with noise a gain of 17.4 % points could be
      estimated with a successful hearing aid fitting.

PMID- 24740735
TI  - Reflections on the role of a traveling wave along the basilar membrane in view of
      clinical and experimental findings.
AB  - Air conduction (AC) is accompanied by displacements of the two cochlear windows,
      bulk fluid flow between them, a pressure difference across the basilar membrane,
      leading to a passive traveling wave along the membrane, which activates the
      cochlear amplifier and enhances the displacements. AC interacts with bone
      conduction (BC) stimulation, so that it has been assumed that BC stimulation also
      involves a passive traveling wave. However, several clinical conditions and
      experimental manipulations provide evidence that a passive traveling wave may not
      be involved in BC stimulation at low intensities. Soft tissue conduction (STC)
      (also called non-osseous bone conduction) involves applying the bone vibrator to
      soft tissues on the head, neck and thorax, eliciting auditory sensation. STC
      stimulation probably does not involve a passive traveling wave. This review
      presents clinical conditions and experimental manipulations which assess the
      contributions of AC, BC and STC stimulation to the passive traveling wave.
      Evidence from the clinic (otosclerosis, round window atresia) and from the
      laboratory (holes in the wall of the inner ear, immobilization of the ossicular
      chain and the windows, discontinuity of the chain, measurement of basilar
      membrane displacements in the absence of the cochlear amplifier) lead to the
      conclusion that a passive basilar membrane traveling wave may not be involved in
      stimulation at low sound intensities. It is suggested that at low sound levels,
      the outer hair cell cochlear amplifier may not be activated by a passive
      traveling wave, but may be directly activated by the fast cochlear fluid
      pressures induced by AC, BC and STC stimulation. On the other hand, at high
      intensities, the cochlea is activated by the slow passive traveling wave. 

PMID- 24740737
TI  - Molecular evolution of GPCRs: Somatostatin/urotensin II receptors.
AB  - Somatostatin (SS) and urotensin II (UII) are members of two families of
      structurally related neuropeptides present in all vertebrates. They exert a large
      array of biological activities that are mediated by two families of G-protein
      coupled receptors called SSTR and UTS2R respectively. It is proposed that the two
      families of peptides as well as those of their receptors probably derive from a
      single ancestral ligand-receptor pair. This pair had already been duplicated
      before the emergence of vertebrates to generate one SS peptide with two receptors
      and one UII peptide with one receptor. Thereafter, each family expanded in the
      three whole-genome duplications (1R, 2R, and 3R) that occurred during the
      evolution of vertebrates, whereupon some local duplications and gene losses
      occurred. Following the 2R event, the vertebrate ancestor is deduced to have
      possessed three SS (SS1, SS2, and SS5) and six SSTR (SSTR1-6) genes, on the one
      hand, and four UII (UII, URP, URP1, and URP2) and five UTS2R (UTS2R1-5) genes, on
      the other hand. In the teleost lineage, all these have been preserved with the
      exception of SSTR4. Moreover, several additional genes have been gained through
      the 3R event, such as SS4 and a second copy of the UII, SSTR2, SSTR3, and SSTR5
      genes, and through local duplications, such as SS3. In mammals, all the genes of
      the SSTR family have been preserved, with the exception of SSTR6. In contrast,
      for the other families, extensive gene losses occurred, as only the SS1, SS2,
      UII, and URP genes and one UTS2R gene are still present. 

PMID- 24740736
TI  - Recent research on the growth plate: Recent insights into the regulation of the
      growth plate.
AB  - For most bones, elongation is driven primarily by chondrogenesis at the growth
      plates. This process results from chondrocyte proliferation, hypertrophy, and
      extracellular matrix secretion, and it is carefully orchestrated by complex
      networks of local paracrine factors and modulated by endocrine factors. We review
      here recent advances in the understanding of growth plate physiology. These
      advances include new approaches to study expression patterns of large numbers of
      genes in the growth plate, using microdissection followed by microarray. This
      approach has been combined with genome-wide association studies to provide
      insights into the regulation of the human growth plate. We also review recent
      studies elucidating the roles of bone morphogenetic proteins, fibroblast growth
      factors, C-type natriuretic peptide, and suppressor of cytokine signaling in the
      local regulation of growth plate chondrogenesis and longitudinal bone growth. 

PMID- 24740738
TI  - Revising the role of the androgen receptor in breast cancer.
AB  - Breast cancer (BC) is traditionally viewed as an oestrogen-dependent disease in
      which the androgen receptor (AR) is inhibitory, counteracting the oncogenic
      activity of oestrogen receptor alpha (ERalpha (ESR1)). Most probably as a result
      of this crosstalk, the AR has prognostic value in ER-positive disease, with AR
      positivity reported to correlate with a better prognosis. Activation of the AR
      pathway has been previously used as a therapeutic strategy to treat BC, but its
      usage declined following the introduction of the anti-oestrogen tamoxifen. More
      recently, it has been demonstrated that a subset of triple-negative BCs
      (molecular apocrine) are dependent upon androgen signalling for growth and
      therapies that inhibit androgen signalling, currently used for the treatment of
      prostate cancer, e.g. the antiandrogen bicalutamide and the CYP17 inhibitor
      abiraterone acetate are undergoing clinical trials to investigate their efficacy
      in this BC subtype. This review summarises the current knowledge of AR activity
      in BC. 

PMID- 24740739
TI  - The intracellular juxtamembrane domain of discoidin domain receptor 2 (DDR2) is
      essential for receptor activation and DDR2-mediated cancer progression.
AB  - Discoidin domain receptors (DDRs) are unusual receptor tyrosine kinases (RTKs)
      that are activated by fibrillar collagens instead of soluble growth factors. DDRs
      play an important role in various cellular functions and disease processes,
      including malignant progression. Compared to other RTKs, DDRs have relatively
      long juxtamembrane domains, which are believed to contribute to receptor
      function. Despite this possibility, the function and mechanism of the
      juxtamembrane domain of DDRs have not yet been fully elucidated. In this study,
      we found that the cytoplasmic juxtamembrane 2 (JM2) region of DDR2 contributed to
      receptor dimerization, which is critical for receptor activation in response to
      collagen stimulation. A collagen-binding assay showed that JM2 was required for
      efficient binding of collagen to the discoidin (DS) domain. Immunohistochemical
      analysis of DDR2 expression using a tissue microarray demonstrated that DDR2 was
      overexpressed in several carcinoma tissues, including bladder, testis, lung,
      kidney, prostate and stomach. In H1299 cells, inhibition of DDR2 activity by
      overexpressing the juxtamembrane domain containing JM2 suppressed collagen
      induced colony formation, cell proliferation and invasion via the inhibition of
      matrix metalloproteinase-2 and matrix metalloproteinase-9. Taken together, our
      results suggest that JM2-mediated dimerization is likely to be essential for DDR2
      activation and cancer progression. Thus, inhibition of DDR2 function using a JM2
      containing peptide might be a useful strategy for the treatment of DDR2-positive
      cancers.

PMID- 24740740
TI  - Neurorestorative targets of dietary long-chain omega-3 fatty acids in
      neurological injury.
AB  - Long-chain omega-3 polyunsaturated fatty acids (LC-O3PUFAs) exhibit therapeutic
      potential for the treatment and prevention of the neurological deficits
      associated with spinal cord injury (SCI). However, the mechanisms implicated in
      these protective responses remain unclear. The objective of the present
      functional metabolomics study was to identify and define the dominant metabolic
      pathways targeted by dietary LC-O3PUFAs. Sprague-Dawley rats were fed rodent
      purified chows containing menhaden fish oil-derived LC-O3PUFAs for 8 weeks before
      being subjected to sham or spinal cord contusion surgeries. We show, through
      untargeted metabolomics, that dietary LC-O3PUFAs regulate important biochemical
      signatures associated with amino acid metabolism and free radical scavenging in
      both the injured and sham-operated spinal cord. Of particular significance, the
      spinal cord metabolome of animals fed with LC-O3PUFAs exhibited reduced glucose
      levels (-48 %) and polar uncharged/hydrophobic amino acids (less than -20 %)
      while showing significant increases in the levels of antioxidant/anti
      inflammatory amino acids and peptides metabolites, including beta-alanine (+24
      %), carnosine (+33 %), homocarnosine (+27 %), kynurenine (+88 %), when compared
      to animals receiving control diets (p < 0.05). Further, we found that dietary LC
      O3PUFAs impacted the levels of neurotransmitters and the mitochondrial
      metabolism, as evidenced by significant increases in the levels of N
      acetylglutamate (+43 %) and acetyl CoA levels (+27 %), respectively.
      Interestingly, this dietary intervention resulted in a global correction of the
      pro-oxidant metabolic profile that characterized the SCI-mediated sensorimotor
      dysfunction. In summary, the significant benefits of metabolic homeostasis and
      increased antioxidant defenses unlock important neurorestorative pathways of
      dietary LC-O3PUFAs against SCI.

PMID- 24740741
TI  - Does IGFR1 inhibition result in increased muscle mass loss in patients undergoing
      treatment for pancreatic cancer?
AB  - BACKGROUND: IGF-1 plays a role in the growth of multiple tumor types, including
      pancreatic cancer. IGF-1 also serves as a growth factor for muscle. The impact of
      therapeutic targeting of IGF-1 on muscle mass is unknown. METHODS: We evaluated
      muscle mass at L3 in patients enrolled in a randomized phase II study of MK-0646
      (M), a monoclonal antibody directed against the IGF-1 protein, in patients with
      metastatic pancreatic cancer (MPC). Two different doses of M were tested, 5 and
      10 mg/kg. We used the Slice-o-matic (ver 4.3) software to segregate CT images
      into muscle and fat components and measured muscle area (cm(2)) at baseline and
      after 2 and 4 months of treatment. Patients received either gemcitabine with
      erlotinib (G + E), G + E + M, or G + M. Differences between the groups were
      compared using t tests. RESULTS: Fifty-three patients had both baseline and 2
      month imaging available for analysis. Of these, 42 received M with their chemo,
      and 11 had G + E only. After 2 months of treatment, both groups demonstrated
      decrease in muscle mass. G + E patients lost 5.6 % of muscle mass; M patients
      lost 9.1 and 8.6 % after treatment with 5 and 10 mg/kg, respectively (p = 0.53).
      Patients demonstrating a response lost less muscle (median 4.6 %) than those with
      stable disease (9.6 %) and progressive disease (8.9 %, p = 0.14). Muscle
      retention from baseline to 2-month imaging, defined as loss of <6 cm(2) of
      muscle, correlated with better survival than those patients demonstrating a
      muscle loss (HR 0.51, p = 0.03). CONCLUSIONS: MPC patients can be expected to
      lose muscle mass even while having clinical benefit (PR or SD) from chemotherapy.
      Muscle loss correlated with a risk of study drop-out and death. There was a non
      significant trend toward greater muscle mass loss in patients on anti-IGF-1R
      therapy. However, it is unclear if this loss translates into functional
      differences between patients.

PMID- 24740743
TI  - Electrical conductivity and glass formation in nitrile-functionalized
      pyrrolidinium bis(trifluoromethylsulfonyl)imide ionic liquids: chain length and
      odd-even effects of the alkyl spacer between the pyrrolidinium ring and the
      nitrile group.
AB  - The electrical conductivity of a series of pyrrolidinium
      bis(trifluoromethylsulfonyl)imide ionic liquids, functionalized with a nitrile
      (cyano) group at the end of an alkyl chain attached to the cation, was studied in
      the temperature range between 173 K and 393 K. The glass formation of the ionic
      liquids is influenced by the length of the alkyl spacer separating the nitrile
      function from the pyrrolidinium ring. The electrical conductivity and the
      viscosity do not show a monotonic dependence on the alkyl spacer length, but
      rather an odd-even effect. An explanation for this behavior is given, including
      the potential energy landscape picture for the glass transition. 

PMID- 24740744
TI  - Aphids as models for ecological and evolutionary studies.

PMID- 24740742
TI  - Osteosarcopenic obesity: the role of bone, muscle, and fat on health.
AB  - Osteopenia/osteoporosis, sarcopenia, and obesity are commonly observed in the
      process of aging, and recent evidence suggests a potential interconnection of
      these syndromes with common pathophysiology. The term osteosarcopenic obesity has
      been coined to describe the concurrent appearance of obesity in individuals with
      low bone and muscle mass. Although our understanding of osteosarcopenic obesity's
      etiology, prevalence, and consequences is extremely limited, it is reasonable to
      infer its negative impact in a population that is aging in an obesogenic
      environment. It is likely that these individuals will present with poorer
      clinical outcomes caused by the cascade of metabolic abnormalities associated
      with these changes in body composition. Clinical outcomes include but are not
      limited to increased risk of fractures, impaired functional status (including
      activities of daily living), physical disability, insulin resistance, increased
      risk of infections, increased length of hospital stay, and reduced survival.
      These health outcomes are likely to be worse when compared to individuals with
      obesity, sarcopenia, or osteopenia/osteoporosis alone. Interventions that utilize
      resistance training exercise in conjunction with increased protein intake appear
      to be promising in their ability to counteract osteosarcopenic obesity. 

PMID- 24740745
TI  - Metastatic melanoma: optimizing outcomes by managing dermatologic toxicities
      associated with novel therapies.
AB  - The last couple of years have seen the beginning of a new era in the treatment of
      metastatic melanoma. This disease is typically characterized by its poor
      prognosis and limited choice of therapy. Two mechanistically diverse classes of
      agents - BRAF inhibitors and immune modulators - have demonstrated an overall
      survival benefit. Along with their significant clinical benefits, there are also
      unique adverse events (AEs) related to these agents. While most of the AEs are
      mild and easily managed with supportive treatment, others require more aggressive
      management strategies. Education of all members of the multidisciplinary care
      team and awareness of these toxicities are crucial in order to optimize patient
      outcomes. The landscape of melanoma is continually evolving as ongoing trials are
      evaluating monotherapy and combination options. While these regimens continue to
      show promise for the future, understanding and managing toxicities of currently
      available therapies is required. 

PMID- 24740746
TI  - An update on the clinical management of cutaneous molluscum contagiosum.
AB  - Molluscum contagiosum is a poxvirus infection of the skin that is commonly
      observed in children. The molluscum contagiosum virus (MCV) expresses several
      gene-products that are involved in its pathogenesis and evasion of the host
      immune system. MCV can be transmitted both to other sites of the body and to
      other individuals through direct physical contact as well as fomites. While
      diagnosis is generally straightforward clinically, management of molluscum
      contagiosum is controversial. Several treatment options are available for the
      destruction of individual lesions, but there is insufficient evidence for
      therapeutic intervention being any more effective than natural, spontaneous
      resolution. Complex cases, such as infection occurring in immunocompromised
      patients and in mucocutaneous sites, require an alternative approach to
      management. Molluscum contagiosum continues to represent a burden on children and
      parents worldwide. 

PMID- 24740747
TI  - Crowdsourcing medical expertise in near real time.
AB  - Given the pace of discovery in medicine, accessing the literature to make
      informed decisions at the point of care has become increasingly difficult.
      Although the Internet creates unprecedented access to information, gaps in the
      medical literature and inefficient searches often leave healthcare providers'
      questions unanswered. Advances in social computation and human computer
      interactions offer a potential solution to this problem. We developed and piloted
      the mobile application DocCHIRP, which uses a system of point-to-multipoint push
      notifications designed to help providers problem solve by crowdsourcing from
      their peers. Over the 244-day pilot period, 85 registered users logged 1544 page
      views and sent 45 consult questions. The median initial first response from the
      crowd occurred within 19 minutes. Review of the transcripts revealed several
      dominant themes, including complex medical decision making and inquiries related
      to prescription medication use. Feedback from the post-trial survey identified
      potential hurdles related to medical crowdsourcing, including a reluctance to
      expose personal knowledge gaps and the potential risk for "distracted doctoring."
      Users also suggested program modifications that could support future adoption,
      including changes to the mobile interface and mechanisms that could expand the
      crowd of participating healthcare providers.

PMID- 24740748
TI  - The novel Shewanella putrefaciens-infecting bacteriophage Spp001: genome sequence
      and lytic enzymes.
AB  - Shewanella putrefaciens has been identified as a specific spoilage organism
      commonly found in chilled fresh fish, which contributes to the spoilage of fish
      products. Limiting S. putrefaciens growth can extend the shelf-life of chilled
      fish. Endolysins, which are lytic enzymes produced by bacteriophages, have been
      considered an alternative to control bacterial growth, and have been useful in
      various applications, including food preservation. We report here, for the first
      time, the complete genome sequence of a novel phage Spp001, which lyses S.
      putrefaciens Sp225. The Spp001 genome comprises a 54,789-bp DNA molecule with 67
      open reading frames and an average total G + C content of 49.42 %. In silico
      analysis revealed that the Spp001 open reading frames encode various putative
      functional proteins, including an endolysin (ORF 62); however, no sequence for
      genes encoding the holin polypeptides, which work in concert with endolysins, was
      identified. To examine further the lytic activity of Spp001, we analyzed the
      lytic enzyme-containing fraction from phages released at the end of the phage
      lytic cycle in S. putrefaciens, using diffusion and turbidimetric assays. The
      results show that the partially purified extract contained endolysin, as
      indicated by a high hydrolytic activity towards bacterial peptidoglycan decrease
      in the OD590 value by 0.160 in 15 min. The results will allow further
      investigation of the purification of natural Spp001 endolysin, the extension of
      Spp001 host range, and the applications of the phage-encoded enzymes.

PMID- 24740749
TI  - 12-month primary patency rates of contemporary endovascular device therapy for
      femoro-popliteal occlusive disease in 6,024 patients: beyond balloon angioplasty.
AB  - BACKGROUND: Endovascular approach to superficial femoral artery (SFA) disease,
      the most common cause of symptomatic peripheral arterial disease, remains fraught
      with high failure rates. Newer devices including second-generation nitinol
      stents, drug-coated stents, drug-coated balloons, covered stents, cryo-therapy,
      LASER, and directional atherectomy have shown promising results. Clinical
      equipoise still persists regarding the optimal selection of devices, largely
      attributable to the different inclusion criteria, study population, length of
      lesions treated, definition of "patency" and "restenosis," and follow-up methods
      in the pivotal trials. METHODS: A prospective protocol was developed. We
      performed a literature search using PubMed from January 2006 to November 2013.
      Published articles including endovascular interventions in SFA or popliteal
      arteries with reported 12-month "primary patency" or "binary restenosis" rates as
      endpoints were included. RESULTS: We identified 6,024 patients in 61 trials
      reporting 12-month primary patency rates in patients with femoropoliteal disease.
      Primary patency rates were (weighted average) 77.2% for nitinol stents, 68.8% for
      covered stents, 84% for drug eluting stents, 78.2% for drug eluting/coated
      balloon, 60.7% for cryoballoon, 51.1% for LASER atherectomy, 63.5% for
      directional atherectomy and 70.2% with a combination of endovascular devices.
      CONCLUSION: The most frequently used endovascular devices yielded various 12
      month primary patency rates ranging from 51% to 85%. The increased variation in
      inclusion criteria, length, and complexity of lesions between studies does not
      allow direct comparison between them. Larger randomized trials in specific
      patient populations comparing those modalities is needed before we can make safe
      recommendation of the superiority of one device over the other.

PMID- 24740750
TI  - High-speed scanning thermal lithography for nanostructuring of electronic
      devices.
AB  - We report a detailed analysis on the use of simultaneous substrate heating in
      conjunction with scanning thermal lithography (SThL) to dramatically increase the
      patterning speed of conventional SThL systems. The investigation consists of
      finite element simulations as well as practical assessments of the speed at which
      different organic precursors are thermally converted to produce standalone
      electrically active and passive nanostructures. As a proof of concept the high
      speed SThL method was used to pattern semiconducting pentacene nanoribbons, which
      were subsequently incorporated into functioning transistors. Simultaneous
      substrate heating was found to allow patterning of functional devices at writing
      speeds >19 times higher than transistors produced at identical speeds but with
      the substrate maintained at room temperature. These fast written transistors
      exhibit 100* higher hole mobility with high on/off current ratio and negligible
      operating hysteresis. The generality of the proposed high-speed SThL method was
      further demonstrated with the rapid patterning of conductive nanostructured metal
      electrodes with excellent spatial resolution employing an appropriate polymer
      precursor as the chemical resist. It is proposed that these advances further
      support the case for using SThL systems as rapid prototypers for low micron and
      nanoscale structures for both direct patterning of precursors and indirect
      patterning of metals and other materials using suitable chemical resist. 

PMID- 24740751
TI  - Microbial diversity in an Armenian geothermal spring assessed by molecular and
      culture-based methods.
AB  - The phylogenetic diversity of the prokaryotic community thriving in the Arzakan
      hot spring in Armenia was studied using molecular and culture-based methods. A
      sequence analysis of 16S rRNA gene clone libraries demonstrated the presence of a
      diversity of microorganisms belonging to the Alphaproteobacteria,
      Betaproteobacteria, Gammaproteobacteria, Epsilonproteobacteria, Firmicutes,
      Bacteroidetes phyla, and Cyanobacteria. Proteobacteria was the dominant group,
      representing 52% of the bacterial clones. Denaturing gradient gel electrophoresis
      profiles of the bacterial 16S rRNA gene fragments also indicated the abundance of
      Proteobacteria, Bacteroidetes, and Cyanobacteria populations. Most of the
      sequences were most closely related to uncultivated microorganisms and shared
      less than 96% similarity with their closest matches in GenBank, indicating that
      this spring harbors a unique community of novel microbial species or genera. The
      majority of the sequences of an archaeal 16S rRNA gene library, generated from a
      methanogenic enrichment, were close relatives of members of the genus
      Methanoculleus. Aerobic endospore-forming bacteria mainly belonging to Bacillus
      and Geobacillus were detected only by culture-dependent methods. Three isolates
      were successfully obtained having 99, 96, and 96% 16S rRNA gene sequence
      similarities to Arcobacter sp., Methylocaldum sp., and Methanoculleus sp.,
      respectively. 

PMID- 24740752
TI  - Ideological and organizational components of differing public health strategies
      for addressing the social determinants of health.
AB  - Despite a history of conceptual contributions to reducing health inequalities by
      addressing the social determinants of health (SDH), Canadian governmental
      authorities have struggled to put these concepts into action. Ontario's-Canada's
      most populous province-public health scene shows a similar pattern. In statements
      and reports, governmental ministries, professional associations and local public
      health units (PHUs) recognize the importance of these issues, yet there has been
      varying implementation of these concepts into public health activity. The purpose
      of this study was to gain insight into the key features responsible for
      differences in SDH-related activities among local PHUs. We interviewed Medical
      Officers of Health (MOH) and key staff members from nine local PHUs in Ontario
      varying in SDH activity as to their understandings of the SDH, public health's
      role in addressing the SDH, and their units' SDH-related activities. We also
      reviewed their unit's documents and their organizational structures in relation
      to acting on the SDH. Three clusters of PHUs are identified based on their SDH
      related activities: service-delivery-oriented; intersectoral and community-based;
      and public policy/public education-focused. The two key factors that
      differentiate PHUs are specific ideological commitments held by MOHs and staff
      and the organizational structures established to carry out SDH-related
      activities. The ideological commitments and the organizational structures of the
      most active PHUs showed congruence with frameworks adopted by national
      jurisdictions known for addressing health inequalities. These include a
      structural analysis of the SDH and a centralized organizational structure that
      coordinates SDH-related activities. 

PMID- 24740753
TI  - Bridge-to-surgery stent placement versus emergency surgery for acute malignant
      colonic obstruction.
AB  - BACKGROUND: Endoscopic self-expanding metal stent (SEMS) placement as a bridge to
      surgery is an option for acute malignant colonic obstruction. There is ongoing
      debate regarding the superiority and oncological safety of SEMS placement
      compared with emergency surgery. This retrospective study aimed to compare
      outcomes of these treatment approaches. METHODS: Patients were identified from
      cohorts treated between 2005 and 2012 in two teaching hospitals, of which one
      used emergency surgery only in patients with large bowel obstruction, whereas the
      other attempted SEMS placement. Only patients treated with curative intent were
      included. RESULTS: The study included 59 patients in whom SEMS placement was
      attempted and 51 who underwent surgery alone. The successful primary anastomosis
      rate was higher in the SEMS group than in the surgery-alone group among patients
      with left-sided obstruction (30 of 43 versus 10 of 34 respectively; P = 0.001),
      whereas stoma formation was less common (11 of 43 versus 23 of 34; P < 0.001).
      Such differences were not apparent in patients with right-sided obstruction.
      Secondary stoma rates were comparable between treatment approaches (left-sided:
      11 of 43 versus 13 of 34, P = 0.322; right-sided: 1 of 16 versus 1 of 17, P =
      1.000). There were no significant differences in morbidity, mortality, recurrence
      or survival. CONCLUSION: Endoscopic SEMS placement increased the primary
      anastomosis rate in patients with left-sided large bowel obstruction.

PMID- 24740754
TI  - Women with heart failure: do they require a special approach for improving
      adherence to self-care?
AB  - The purpose of this review is to evaluate research regarding whether women with
      heart failure (HF) need a special approach for improving their adherence to self
      care. Prior research has sampled mostly white, male populations and these results
      have been generalized to the population of all HF patients. After age 65, women
      are at a higher risk than men for developing HF. Once women develop HF they are
      more likely than men with HF to experience greater symptom burden, re
      hospitalizations, social isolation, and higher mortality rates. In this review we
      will explore barriers and facilitators that women experience when performing self
      care, and whether they need individualized interventions or approaches to care
      that are different from those for male patients with HF. Special approaches such
      as assessment of social support and self-care counseling when treating women with
      HF will be discussed, as this may improve women's adherence, thereby slowing the
      symptom burden and disease progression. 

PMID- 24740755
TI  - Manganese superoxide dismutase knock-down in 3T3-L1 preadipocytes impairs
      subsequent adipogenesis.
AB  - Adipogenesis is associated with the upregulation of the antioxidative enzyme
      manganese superoxide dismutase (MnSOD) suggesting a vital function of this enzyme
      in adipocyte maturation. In the current work, MnSOD was knocked-down with small
      interference RNA in preadipocytes to study its role in adipocyte differentiation.
      In mature adipocytes differentiated from these cells, proteins characteristic for
      mature adipocytes, which are strongly induced in late adipogenesis like
      adiponectin and fatty acid-binding protein 4, are markedly reduced. Triglycerides
      begin to accumulate after about 6 days of the induction of adipogenesis, and are
      strongly diminished in cells with low MnSOD. Proteins upregulated early during
      differentiation, like fatty acid synthase and cytochrome C oxidase-4, are not
      altered. Cell viability, insulin-mediated phosphorylation of Akt, antioxidative
      capacity (AOC), superoxide levels, and heme oxygenase 1 with the latter being
      induced upon oxidative stress are not affected. L-Buthionine-(S,R)-sulfoximine
      (BSO) depletes glutathione and modestly lowers AOC of mature adipocytes. Addition
      of BSO to 3T3-L1 cells 3 days after the initiation of differentiation impairs
      triglyceride accumulation and expression of proteins induced in late
      adipogenesis. Of note, proteins that increased early during adipogenesis are also
      diminished, suggesting that BSO causes de-differentiation of these cells.
      Preadipocyte proliferation is not considerably affected by low MnSOD and BSO.
      These data suggest that glutathione and MnSOD are essential for adipogenesis.

PMID- 24740756
TI  - Redox regulation of antioxidant enzymes: post-translational modulation of
      catalase and glutathione peroxidase activity by resveratrol in diabetic rat
      liver.
AB  - Resveratrol is a strong antioxidant that exhibits blood glucose-lowering effects,
      which might contribute to its usefulness in preventing complications associated
      with diabetes. The present study aimed to investigate resveratrol effects on
      catalase (CAT) and glutathione peroxidase (GPx) gene and protein expression,
      their phosphorylation states and activities in rat liver of STZ-induced diabetes.
      Diabetes increased the levels of total protein phosphorylation and p-CAT, while
      mRNA expression, protein levels, and activity were reduced. Although diabetes
      induced transcriptional repression over GPx, it did not affect the protein levels
      and activity. When resveratrol was administered to diabetic rats, an increase in
      activity was associated with an increase in p-GPx levels. Decrease in Sirtuin1
      (SIRT1) and nuclear factor erythroid 2-related factor (Nrf2) and increase in
      nuclear factor kappa B (NFkappaB) gene expression in diabetes were associated
      with a decrease in CAT and GPx mRNA expression. A possible compensatory mechanism
      for reduced gene expression of antioxidant enzymes is proved to be nuclear
      translocation of redox-sensitive Nrf2 and NFkappaB in diabetes which is confirmed
      by the increase in nuclear and decrease in cytoplasmic protein levels of Nrf2 and
      NFkappaB. Taken together, these findings revealed that an increase in the
      oxidized state in diabetes intricately modified the cellular phosphorylation
      status and regulation of antioxidant enzymes. Gene regulation of antioxidant
      enzymes was accompanied by nuclear translocation of Nrf2 and NFkappaB.
      Resveratrol administration also activated a coordinated cytoprotective response
      against diabetes-induced changes in liver tissues. 

PMID- 24740757
TI  - Glycine aggravates ischemia reperfusion-induced acute kidney injury through N
      Methyl-D-Aspartate receptor activation in rats.
AB  - The present study was designed to investigate the role of glycine in ischemia
      reperfusion-induced acute kidney injury (AKI) in rats. The AKI was induced in
      rats by occluding renal pedicles for 40 min followed by reperfusion for 24 h. The
      AKI was assessed by measuring creatinine clearance, blood urea nitrogen, plasma
      uric acid, potassium, fractional excretion of sodium, and microproteinuria. The
      oxidative stress in renal tissues was assessed by quantification of
      myeloperoxidase activity, thiobarbituric acid-reactive substances, superoxide
      anion generation, and reduced glutathione level. Glycine (100, 200, and 400
      mg/kg, i.p.) was administered to rats 30 min before subjecting to AKI. The
      glycinergic receptor blocker, strychnine (0.75 mg/kg i.p.), and glycine-binding
      site blocker at N-methyl-D-aspartate (NMDA) receptor, kynurenic acid (300 and 600
      mg/kg i.p.), were used in the present study. The ischemia reperfusion induced AKI
      as witnessed by significant change in plasma, urinary, and tissue parameters
      employed in the present study. Glycine treatment increased ischemia reperfusion
      induced AKI. The treatment with strychnine did not show any protection, whereas
      kynurenic acid ameliorated renal ischemia reperfusion-induced AKI. The results
      obtained in present study suggest that glycine increases ischemia reperfusion
      induced renal damage through NMDA receptor agonism rather than strychnine
      sensitive glycinergic receptors. Hence, it is concluded that glycine aggravates
      ischemia reperfusion-induced AKI. In addition, the activation of strychnine
      insensitive glycine-binding site of NMDA receptors is responsible for its renal
      damaging effect rather than strychnine-sensitive glycinergic receptors.

PMID- 24740758
TI  - Stem cell and extracellular matrix-related molecules increase following melatonin
      treatment in the skin of postmenopausal rats.
AB  - The menopause has a negative effect in the skin. Melatonin affects skin functions
      and structures through actions mediated by cell-surface and putative-nuclear
      receptors expressed in skin cell. We have therefore determined the effects of
      melatonin treatment on stem cell in the epidermis and extracellular matrix
      related molecules in the dermis the skin of postmenopausal rats. A total of 45
      female rats were divided into 5 groups: control group, group A [ovariectomy
      (OVX)], group B (OVX +10 mg/kg/day melatonin), group C (OVX +30 mg/kg/day
      melatonin), group S (sham operated + 10 mg/kg/day melatonin). Ventral skin
      samples were excised at 12th week after ovariectomy. Hematoxylin-eosin, periodic
      acid- methylamine silver, elastic van Gieson staining techniques were used to
      measure histomorphometrically the thickness of elastic fibers and basement
      membrane, depths of the epidermis, dermis, and subcutaneous fat layer.
      Immunohistochemical staining methods were used for fibroblast growth factor beta
      (FGF beta), collagen type I, fibronectin, beta-catenin, c-kit, c-Myc evaluation.
      Epidermal thickness, subcutaneous fat layer, and elastic fibers were
      significantly decreased in group C, and there was a significant increase after
      melatonin treatment. Although there was no difference in dermal thickness of
      group C, melatonin also significantly increased the dermal thickness. High FGF
      beta, type I collagen, fibronectin, beta-catenin, c-Myc immunoreactivity
      developed following melatonin in all groups. Thus melatonin treatment of
      postmenopausal rats was mostly due to the decrease of stem cell and extracellular
      matrix-related molecules in the skin.

PMID- 24740759
TI  - Apparent diffusion coefficient quantification as an early imaging biomarker of
      response and predictor of survival following yttrium-90 radioembolization for
      unresectable infiltrative hepatocellular carcinoma with portal vein thrombosis.
AB  - PURPOSE: To investigate early diffusion-weighted imaging (DWI) at 30-days post
      yttrium-90 (Y-90) radioembolization as a predictor of treatment response and
      survival in unresectable infiltrative hepatocellular carcinoma (HCC) with portal
      vein thrombosis (PVT). MATERIALS AND METHODS: In a prospective study, 18
      consecutive patients with unresectable infiltrative HCC and PVT underwent Y-90
      therapy. MR imaging was obtained pre Y-90, and at 1 and 3 months post-therapy
      with DWI fat-suppressed tri-directional diffusion gradient (b = 50, 400, 800
      s/mm(2)). Response was evaluated using target mRECIST and EASL. Relative change
      in apparent diffusion coefficient (ADC) value of tumors was evaluated.
      Statistical analysis using receiver operator characteristic curves was performed.
      Paired t test and Pearson correlation coefficient (r) were used to assess intra-
      and inter-observer variability. Survival analysis was performed using Kaplan
      Meier estimation and log-rank test. RESULTS: Mean ADC values of all HCC's at
      baseline and at 30-days post-Y90 therapy was 0.86 * 10(-3) and 1.17*10(-3)
      mm(2)/s, respectively (p < 0.001). Tumors with objective response by mRECIST had
      significantly increased ADC value when compared to "non-responders" (1.27 vs.
      1.05*10(-3) mm(2)/s, p = 0.002). A >30% increase in ADC value at 30-days was
      found to be at least 90% sensitive in predicting response at 90 days. A >30%
      increase in ADC value at 30-days predicted significantly prolonged survival.
      CONCLUSION: A 30% increase in ADC value at 30-days measured post Y90 is a
      reproducible early imaging response biomarker predicting tumor response and
      prolonged survival following Y-90 therapy in infiltrative HCC with PVT.

PMID- 24740761
TI  - The degree of abdominal imaging (AI) subspecialization of the reviewing
      radiologist significantly impacts the number of clinically relevant and
      incidental discrepancies identified during peer review of emergency after-hours
      body CT studies.
AB  - PURPOSE: To evaluate if and to what extent the degree of subspecialization in
      abdominal imaging (AI) affects rates of discrepancies identified on review of
      body CT studies initially interpreted by board-certified radiologists not
      specialized in AI. METHOD AND MATERIALS: AI division radiologists at one academic
      medical center were classified as primary or secondary members of the division
      based on whether they perform more or less than 50% of their clinical duties in
      AI. Primary AI division radiologists were further subdivided based on whether or
      not they focus their clinical duties almost exclusively in AI. All AI
      radiologists performed subspecialty review of all after-hours body CT studies
      initially interpreted by any non-division radiologist. The discrepancies
      identified in the subspecialty review of consecutive after-hours body CT scans
      performed between 7/1/10 and 12/31/10 were analyzed and placed into one of three
      categories: (1) discrepancies that potentially affect patient care ("clinically
      relevant discrepancies", or CRD); (2) discrepancies that would not affect patient
      care ("incidental discrepancies", or ID); and (3) other types of comments. Rates
      of CRD and ID detection were compared between subgroups of Abdominal Imaging
      Division radiologists divided by the degree of subspecialization. RESULTS: 1303
      studies met the inclusion criteria. Of 742 cases reviewed by primary members of
      the AI division, 33 (4.4%) had CRD and 78 (10.5%) had ID. Of 561 cases reviewed
      by secondary members of the AI division, 11 (2.0%) had CRD and 36 (6.5%) had ID.
      The differences between the groups for both types of discrepancies were
      statistically significant (p = 0.01). When primary members of the AI division
      were further subdivided based on extent of clinical focus on abdominal imaging,
      rates of CRD and ID detection were higher for the subgroup with more clinical
      focus on abdominal imaging. CONCLUSION: The degree of AI subspecialization
      affects the rate of clinically relevant and ID identified in body CT
      interpretations initially rendered by board certified but non-abdominal imaging
      subspecialized radiologists.

PMID- 24740762
TI  - Chemoselective intermolecular alpha-arylation of amides.
AB  - A new approach for the fully chemoselective alpha-arylation of amides is
      presented. By means of electrophilic amide activation, aryl groups can be
      regioselectively introduced alpha- to amides, even in the presence of esters and
      alkyl ketones. Mechanistic studies reveal key reaction intermediates and
      emphasize a remarkably subtle base effect in this transformation. 

PMID- 24740760
TI  - Abnormal findings on multiparametric prostate magnetic resonance imaging predict
      subsequent biopsy upgrade in patients with low risk prostate cancer managed with
      active surveillance.
AB  - PURPOSE: To determine the ability of multiparametric MR imaging to predict
      disease progression in patients with prostate cancer managed by active
      surveillance. METHODS: Sixty-four men with biopsy-proven prostate cancer managed
      by active surveillance were included in this HIPPA compliant, IRB approved study.
      We reviewed baseline MR imaging scans for the presence of a suspicious findings
      on T2-weighted imaging, MR spectroscopic imaging (MRSI), and diffusion-weighted
      MR imaging (DWI). The Gleason grades at subsequent biopsy were recorded. A Cox
      proportional hazard model was used to determine the predictive value of MR
      imaging for Gleason grades, and the model performance was described using
      Harrell's C concordance statistic and 95% confidence intervals (CIs). RESULTS:
      The Cox model that incorporated T2-weighted MR imaging, DWI, and MRSI showed that
      only T2-weighted MR imaging and DWI are independent predictors of biopsy upgrade
      (T2; HR = 2.46; 95% CI 1.36-4.46; P = 0.003-diffusion; HR = 2.76; 95% CI 1.13
      6.71; P = 0.03; c statistic = 67.7%; 95% CI 61.1-74.3). There was an increasing
      rate of Gleason score upgrade with a greater number of concordant findings on
      multiple MR sequences (HR = 2.49; 95% CI 1.72-3.62; P < 0.001). CONCLUSIONS:
      Abnormal results on multiparametric prostate MRI confer an increased risk for
      Gleason score upgrade at subsequent biopsy in men with localized prostate cancer
      managed by active surveillance. These results may be of help in appropriately
      selecting candidates for active surveillance.

PMID- 24740763
TI  - Synthesis and elaboration of all-cis-1,2,4,5-tetrafluoro-3-phenylcyclohexane: a
      polar cyclohexane motif.
AB  - A stereocontrolled synthesis of all-cis-1,2,4,5- tetrafluoro-3-phenylcyclohexane
      is developed as the first functionalised example of this polar cyclohexane motif.
      The dipolar nature of the ring, arising due to two 1,3-diaxial C-F bonds, is
      revealed in the solid-state (X-ray) structure. The orthogonal conformation of the
      aryl and cyclohexyl rings in all-cis-1,2,4,5-tetrafluoro-3-phenylcyclohexane, and
      in an ortho-nitro derivative, result in intramolecular (1h)JHF and (2h)JCF  NMR
      couplings relayed through hydrogen bonding. The aryl group of all-cis-1,2,4,5
      tetrafluoro-3-phenylcyclohexane is elaborated in different ways to demonstrate
      the versatility of this compound for delivering the motif to a range of molecular
      building blocks.

PMID- 24740764
TI  - Influence of HPV type on prognosis in patients diagnosed with invasive cervical
      cancer.
AB  - While much is known about the influence of HPV type on the progression of pre
      invasive cervical lesions, the impact of HPV type on cervical cancer prognosis is
      less evidenced. Thus, we assessed the impact of HPV type on the survival of women
      diagnosed with cervical cancer. A total of 370 cases of cervical cancer were
      assessed. Univariate analysis is presented using Kaplan-Meier survival curves and
      log-rank statistics and multivariable Cox proportional hazard models were
      generated using age group, socio-economic deprivation, FIGO stage,
      differentiation and HPV type. HPV grouping was considered in a number of ways
      with particular reference to the presence or absence of HPV 16 and/or 18. In the
      univariate analysis, FIGO, age at diagnosis and treatment were associated with
      poorer survival (p < 0.0001) as was absence of HPV 16 and/or 18 (p = 0.0460). The
      25% mortality time in the non-HPV 16/18 vs. HPV16/18 positive group was 615 days
      and 1,307 days respectively. An unadjusted Cox PH model based HPV16/18 vs. no HPV
      16/18 resulted in a hazard ratio of 0.669 (0.450, 0.995). Adjusting for
      deprivation, FIGO and age group resulted in a hazard ratio of 0.609 (0.395,
      0.941) p = 0.025. These data indicate that cancers associated with HPV 16 and/or
      18 do not confer worse survival compared to cancers associated with other types,
      and may indicate improved survival. Consequently, although HPV vaccine is likely
      to reduce the incidence of cervical cancer it may not indirectly improve cervical
      cancer survival by reducing the burden of those cancers caused by HPV16/18.

PMID- 24740766
TI  - Editorial: advances in neonatology.

PMID- 24740765
TI  - Expression of heat shock proteins (hsp) 27 and 70 in various organ systems in
      cases of death due to fire.
AB  - The expression of heat shock proteins (hsp) increases in case of variable types
      of endogenous and exogenous cellular stress, as for example thermal stress.
      Immunohistochemical staining with hsp antibodies can visualize these stress
      proteins. Fifty-three cases of death due to heat and a control group of 100
      deaths without any antemortem thermic stress were examined regarding hsp27 and
      hsp70 expression in myocardial, pulmonary, and renal tissues. The results
      revealed a correlation between hsp expression, survival time, and cause of death.
      In cases of death due to fire, the expression of hsp is more extensive than in
      the control group, especially in pulmonary and renal tissues. The
      immunohistochemical investigation of an hsp expression can support the proof of
      vitality in cases of death related to fire. 

PMID- 24740767
TI  - Lipid-based formulations solidified via adsorption onto the mesoporous carrier
      Neusilin(r) US2: effect of drug type and formulation composition on in vitro
      pharmaceutical performance.
AB  - The current study determined the extent to which the desorption of lipid-based
      formulations (LBFs) from a mesoporous magnesium aluminometasilicate (Neusilin(r)
      US2) carrier is governed by drug properties, LBF composition, and LBF-to
      adsorbent ratio. A secondary objective was to evaluate the impact of testing
      parameters (medium composition, pH, dilution, and agitation) on in vitro LBF
      performance. Two self-emulsifying LBFs, with high/low lipid-surfactant ratios
      were studied in detail using danazol, fenofibrate, cinnarizine, and mefenamic
      acid as model drugs. A wider range of 38 different danazol-containing LBF were
      also evaluated, where desorption was evaluated immediately after preparation and
      after 1 month of storage. The results revealed that incomplete desorption from
      Neusilin(r) was a feature of all drugs and LBFs tested. Desorption was
      insensitive to agitation but increased under conditions where ionizable drugs
      were charged. In addition, formulations containing a higher proportion (>30%) of
      hydrophilic surfactant consistently exhibited higher desorption, and were least
      susceptible to decreased desorption on storage. In summary, although Neusilin(r)
      is an effective vehicle for LBF solidification, its use is accompanied by a risk
      of incomplete desorption of the vehicle from the carrier, irrespective of the
      drug. Lipid Formulation Classification System (LFCS)Type IIIB LBFs comprising
      higher quantities of hydrophilic surfactants appear to desorb most from
      Neusilin(r). (c) 2014 Wiley Periodicals, Inc. and the American Pharmacists
      Association J Pharm Sci. 

PMID- 24740768
TI  - [Characterization of human hydatidosis mortality: Chile, 2000-2010].
AB  - BACKGROUND: Hydatidosis as a worldwide zoonosis with a high socio-economic impact
      in Chile and other countries for which it is a notifiable human disease in our
      country. OBJECTIVE: To characterize death rates by hydatidosis and whether there
      are differences according to the region of residence. MATERIAL: A descriptive
      analysis using Data System Deaths (2000-2010) was performed. RESULTS: The total
      number of deaths was 293 (56% male). The mortality rate changed from 0.16 in 2000
      to 0.11 in 2010 per 100.000 inhabitants. The main diagnosis corresponded to B67.9
      (Echinococcosis, other and unspecified). Most fatal cases had a basic level of
      education and the Araucania Region had the highest mortality rate. There was a
      loss of life of 5022.04 years by the premature death of 293 people, with a ratio
      of 0.31 PYLL years lost per 1000 inhabitants. In the Araucania Region this ratio
      increased to 1.03 PYLL years lost per 1000 inhabitants. CONCLUSIONS: The
      mortality rate tends to decrease, however this trend might mask regional
      differences. It should be noted that deaths caused by hydatidosis are preventable
      deaths and therefore unjust. Finally, the mortality analysis is important to
      better understand the burden of the disease and evaluate the effectiveness of
      public health interventions.

PMID- 24740769
TI  - [Nosocomial infections after cardiac surgery in infants and children with
      congenital heart disease].
AB  - INTRODUCTION: Nosocomial infections generate high morbidity and mortality in
      children undergoing cardiac surgery. OBJECTIVE: To determine risk factors for
      nosocomial infections in children after congenital heart surgery. METHODS: A
      retrospective case-control study, in patients younger than 15 years undergoing
      surgery for congenital heart disease from January 2007 to December 2011 admitted
      to the Pediatric Critical Patient Unit (UPC-P) in a university hospital. For
      cases, the information was analyzed from the first episode of infection. RESULTS:
      39 patients who develop infections and 39 controls who did not develop infection
      were enrolled. The median age of cases was 2 months. We identified a number of
      factors associated with the occurrence of infections, highlighting in univariate
      analysis: age, weight, univentricular heart physiology, complexity of the
      surgical procedure according to RACHS-1 and cardiopulmonary bypass (CPB) time >=
      200 minutes. Multivariate analysis identified CPB time >= 200 minutes as the
      major risk factor, with an OR of 11.57 (CI: 1.04 to 128.5). CONCLUSION: CPB time
      >= 200 minutes was the mayor risk factor associated with the development of
      nosocomial infections.

PMID- 24740770
TI  - [Presence of Bejing genotype among Mycobacterium tuberculosis strains in two
      centres of the Region Metropolitana of Chile].
AB  - BACKGROUND: Genotyping of Mycobacterium tuberculosis complex (cMtb) allows us to
      know geographically predominant lineages. Some lineages spread more rapidly and
      are associated with multidrug resistance, particularly Beijing, which has been
      reported in Latin America (Peru). There is little information about this topic in
      Chile and there are no reports of the presence of the Beijing genotype. AIM: To
      determine the most prevalent lineages in the Metropolitan Region of Chile with
      emphasis on the search for Beijing in two health centers. METHODS: Two
      complementary molecular methods were used: spoligotyping, based on the variations
      of the direct repeat regions in the genome of cMtb and MIRU-VNTR, based in the
      variable number of tandem repeats of mycobacterial interspersed repetitive units,
      and subsequent analysis in international databases. A designed lineage was
      assigned to 37 of the 43 strains studied (86%); 6 isolates could not be assigned
      to any genotype. LAM and T genotype were the most frequent (39.5 and 32.5%,
      respectively) followed by Haarlem (7.0%), Beijing (4.7%) and X (2.3%).
      CONCLUSION: We describe for the first time the presence of the Beijing genotype
      in Chile. cMtb molecular surveillance should be implemented in our country in
      order to know the dynamics of its transmission.

PMID- 24740771
TI  - [Antifungal activity of melanin in clinical isolates of Candida spp].
AB  - BACKGROUND: Melanocytes are cells located in epidermis and mucous membranes that
      synthesize melanin and cytokines. It is known that melanin has antimicrobial
      activity and that melanocytes are melanized in presence of microbial molecules.
      OBJECTIVE: To study the antifungal activity of melanin on Candida spp.
      METHODOLOGY: The minimum inhibitory concentration (MIC) to melanin was determined
      in 4 Candida ATCC strains (C. albicans SC5314, C. parapsilosis 22019, C. glabrata
      2001, C. krusei 6258) and 56 clinical isolates of Candida spp. (33 C. albicans,
      12 C. glabrata, 3 C. famata, 3 C. krusei, 3 C. parapsilosis, 2 C. tropicalis)
      using a broth microdilution method. In addition, the antifungal activity of
      melanocytes and mice melanoma cells was tested against C. albicans. RESULTS:
      Melanin inhibited the tested isolates, including the susceptible dose-dependent
      and fluconazole-resistant strains; MIC range and MIC50 were 0.09-50 MUg/mL and
      6.25 MUg/mL, respectively. Pigmented cells lysates inhibited C. albicans.
      CONCLUSIONS: Melanin is able to inhibit clinical isolates of Candida spp.
      Melanization could be an important protective mechanism of melanocytes.

PMID- 24740772
TI  - [Protective role of high density lipoproteins in sepsis: basic issues and
      clinical implications].
AB  - High density lipoproteins (HDL) are responsible of reverse cholesterol transport
      and play an important antiatherogenic role. In recent years, several studies
      suggest that HDL have additional functions, including a possible anti
      inflammatory activity in infectious conditions. Furthermore, available evidence
      indicates that the presence of lipopolysaccharide (LPS) within the circulation
      during infectious states induced by gram-negative bacteria may be involved in the
      decrease in HDL cholesterol levels and changes in lipoprotein composition, which
      have been associated with a higher mortality due to sepsis in animal models and
      in humans. In this article, we review this subject and also discuss possible
      mechanisms that explain the positive impact achieved by native HDL, reconstituted
      HDL, or HDL apolipoprotein peptides on the inflammatory response and mortality in
      models of endotoxemia. In this regard, it has been proposed that one of the
      mechanisms by which HDL protect against sepsis may be mediated by its binding
      ability and/or neutralizing capacity on LPS, avoiding an excessive response of
      the immune system. Thus, increasing blood levels of HDL and/or parenteral HDL
      administration may represent a new anti-inflammatory tool for managing septic
      states in humans. 

PMID- 24740773
TI  - [High frequency of hypovitaminosis D and low bone mineral density in a sample of
      HIV-infected men in Chile].
AB  - OBJECTIVES: The aim of this study was to determine the frequency of
      hypovitaminosis D and low bone mineral density in a sample of patients within our
      HIV cohort. METHODS: A random sample of 16 HIV-infected patients was selected for
      evaluation of levels of Vitamin D and bone mineral density with dual X ray
      absorptiometry. RESULTS: Within this sample of patients, 94% had low levels of
      vitamin D. Among them, eight had insufficient levels (10-30 ng/mL) and seven had
      deficient levels (less than 10 ng/mL) of this vitamin. Ten out of sixteen (63%)
      had an abnormal dual X ray absorptiometry (osteopenia or osteoporosis). All
      patients with osteopenia or osteoporosis had low levels of vitamin D, were on CDC
      stage A, had a CD4+ count greater than 350 cells/mm3 and HIV viral load less than
      50 copies/mL. CONCLUSIONS: Low bone mineral density and hypovitaminosis D is
      highly frequent in this sample of HIV-infected patients in Chile.

PMID- 24740774
TI  - [Sarcoptic mange: report of an outbreak in a family and their pet].
AB  - Scabies caused by the genus Sarcoptes scabiei var canis is a prevalent infection
      in dogs and affects abandoned, malnourished and overcrowded animals, causing hair
      loss and an intensely pruritic crusting dermatitis. In humans the manifestation
      is a self-limiting pruritic dermatitis, but persistent cases are described. An
      outbreak of sarcoptic mange is reported in a family group (seven people,
      including a 5 month infant and his mother). The infective source was their own
      house dog who was taken from the street. The diagnosis was confirmed by the
      detection of mites and eggs in the acarotest of the dog and mites of S. scabei in
      the infant. Sarcoptic mange should be suspected in individuals with allergic
      dermatitis who have contact with dogs. Treatment in humans is usually symptomatic
      and may need miticides if the infection persists. The control of the disease
      requires an appropriate pet treatment. 

PMID- 24740775
TI  - [Public statement of the Chilean Infectious Diseases Society about changes to the
      national schedule of vaccination against meningococcal disease].

PMID- 24740776
TI  - [Latinamerican guidelines of RIICER for diagnosis of tick-borne rickettsioses].
AB  - Tick-borne rickettsioses are worldwide infectious diseases that are considered
      emerging and re-emerging. Until recently the only tick-borne rickettsiosis
      present in Latin America was Rickettsia rickettsii infection, but to date, with
      the incorporation of new tools as PCR and sequencing and the quick cellular close
      tube cultures (Shell-vial), new species has been involved as human pathogens. In
      these guidelines, we offer an update of the microbiological assays for diagnosing
      rickettsioses. Besides we have included a section in which the most important
      hard ticks involved in human rickettsioses in Latinoamerica are detailed. 

PMID- 24740777
TI  - [Children with asplenia or hyposplenia: Preventing overwhelming post splenectomy
      infection].
AB  - The spleen's ability to prevent overwhelming post-splenectomy infection (OPSI) is
      mainly given by its capacity to filter and phagocyte bacterial elements from the
      blood, remove foreign elements from it, and the early production of opsonins. The
      anatomic absence of the spleen is usually secondary to a surgical resection, but
      it could also be congenital. Streptococcus pneumoniae has been identified as the
      main agent of OPSI in asplenic patients with an extremely high global mortality
      associated. This article is an exhaustive review of the current evidence and
      recommendations available for prevention of invasive infections in asplenic
      patients. 

PMID- 24740778
TI  - [Invasive candidiasis in newborns: diagnosis, treatment and prophylaxis].
AB  - Invasive fungal infections have become an increasingly common problem in neonatal
      intensive care units (NICU). Invasive candidiasis (IC) is associated with
      substantial morbidity and mortality rates, especially in pre-term infants. The
      aim of this review is to suggest actions in monitoring, prevention, treatment and
      follow up of IC in the newborn infant. 

PMID- 24740779
TI  - [Gender Fusarium].

PMID- 24740780
TI  - [Fever of unknown origin: a challenge for the pediatric infectious diseases
      specialist].
AB  - INTRODUCTION: Prolonged febrile syndrome (PFS) is defined as fever 7-10 days,
      with initial study does not allow etiologic diagnosis. OBJECTIVE: To describe the
      main causes of the PFS and its temporal behavior in Pediatric Infectious Diseases
      Unit Outpatient Care of Complejo Asistencial Dr. Sotero del Rio (CASR). PATIENTS
      AND METHODS: A descriptive, prospective study between january 2007-december 2012,
      about 153 patients from 6 weeks to 14 years 11 months old, diagnosed with PFS,
      tab completing clinical and laboratory monitoring. RESULTS: etiology was obtained
      in 67.9%, the causes were infection (88.4%), neoplasms (4.8%), rheumatological
      (4.8%) and Kawasaki disease (2.8%). The most important infectious causes were
      enteric fevers (typhoid and paratyphoid) (18.4%), urinary tract infection
      (11.9%), Bartonella henselae infections and adenovirus (8.7%) each one and
      Epstein Barr virus (7.6%). Ninety eight percent of patients had complete
      resolution, 60.7% did not require hospitalization and mortality was 0%.
      DISCUSSION: As in previous pediatric clinical series the infections were the most
      frequent causes. Enteric fever persists as principal cause, however, the
      epidemiological evidence is oscillating in time endorsing the local statistics
      can count over the years to improve the diagnostic and therapeutic approach.

PMID- 24740781
TI  - [Struggle against infectious diseases in children in the Magallanes region:
      death, passion and life. (Part II)].
AB  - The first part of this work was published in the previous issue of this magazine.
      In order to finalize with the historical review of infectious diseases which have
      been determining factors on regional infant mortality, we analyze firstly the
      case of religious missions and its impact on the rapid extinction of Patagonian
      Indians. Secondly, we review the health situation of Punta Arenas during the
      first half of the 20th century, switching from a high mortality rate from
      infectious or contagious diseases, to a remarkable improvement in this issue,
      coming to bear the best health indicators in the country. 

PMID- 24740782
TI  - [A multicenter study using positive deviance for improving hand hygiene
      compliance].

PMID- 24740783
TI  - [Efficacy of an infection control program in reducing ventilator-associated
      pneumonia in a Chinese neonatal intensive care unit].

PMID- 24740784
TI  - [Tribute to Beatriz Gilabert Fierro: pioneer of modern clinical microbiology in
      Chile].

PMID- 24740785
TI  - [About pertussis booster vaccination in Chile].

PMID- 24740786
TI  - Recruitment and subsequent proliferation of bone marrow-derived cells in the
      postischemic kidney are important to the progression of fibrosis.
AB  - Acute kidney injury (AKI) is an independent risk factor of the development of
      chronic kidney disease. Kidney fibrosis is a typical feature of chronic kidney
      disease and is characterized as an expansion of the interstitium due to increases
      in extracellular matrix molecules and interstitial cells caused by accumulations
      of extrarenal cells and by the proliferation or differentiation of intrarenal
      cells. However, the role of bone marrow-derived cells (BMDCs) in AKI-induced
      kidney fibrosis remains to be defined. Here, we investigated the role of BMDCs in
      kidney fibrosis after ischemia-reperfusion injury (IRI)-induced AKI in green
      fluorescent protein (GFP)-expressing bone marrow chimeric mice. IRI resulted in
      severe fibrotic changes in kidney tissues and dramatically increased interstitial
      cell numbers. Furthermore, GFP-expressing BMDCs accounted for >80% of
      interstitial cells in fibrotic kidneys. Interstitial GFP-expressing cells
      expressed alpha-smooth muscle actin (a myofibroblast marker), fibroblast-specific
      protein-1 (a fibroblast marker), collagen type III, and F4/80 (a macrophage
      marker). Over 20% of interstitial cells were bromodeoxyuridine-incorporating
      (proliferating) cells, and of these, 80% cells were GFP-expressing BMDCs. Daily
      treatment of IRI mice with apocynin (a NADPH oxidase inhibitor that functions as
      an antioxidant) from the day after surgery until euthanization slightly inhibited
      these changes with a small reduction of fibrosis. Taken together, our findings
      show that BMDCs make a major contribution to IRI-induced fibrosis due to their
      infiltration, subsequent differentiation, and proliferation in injured kidneys,
      suggesting that BMDCs be considered an important target for the treatment of
      kidney fibrosis.

PMID- 24740787
TI  - Active removal of inorganic phosphate from cerebrospinal fluid by the choroid
      plexus.
AB  - The P(i) concentration of mammalian cerebrospinal fluid (CSF) is about one-half
      that of plasma, a phenomenon also shown here in the spiny dogfish, Squalus
      acanthias. The objective of the present study was to characterize the possible
      role of the choroid plexus (CP) in determining CSF P(i) concentration. The large
      sheet-like fourth CP of the shark was mounted in Ussing chambers where
      unidirectional (33)P(i) fluxes revealed potent active transport from CSF to the
      blood side under short-circuited conditions. The flux ratio was 8:1 with an
      average transepithelial resistance of 87 +/- 17.9 Omega.cm(2) and electrical
      potential difference of +0.9 +/- 0.17 mV (CSF side positive). Active P(i)
      absorption from CSF was inhibited by 10 mM arsenate, 0.2 mM ouabain, Na(+)-free
      medium, and increasing the K(+) concentration from 5 to 100 mM. Li(+) stimulated
      transport twofold compared with Na(+)-free medium. Phosphonoformic acid (1 mM)
      had no effect on active P(i) transport. RT-PCR revealed both P(i) transporter
      (PiT)1 and PiT2 (SLC20 family) gene expression, but no Na(+)-P(i) cotransporter
      II (SLC34 family) expression, in the shark CP. PiT2 immunoreactivity was shown by
      immunoblot analysis and localized by immunohistochemistry in (or near) the CP
      apical microvillar membranes of both the shark and rat. PiT1 appeared to be
      localized primarily to vascular endothelial cells. Taken together, these data
      indicate that the CP actively removes P(i) from CSF. This process has transport
      properties consistent with a PiT2, Na(+)-dependent transporter that is located in
      the apical region of the CP epithelium.

PMID- 24740788
TI  - COX-2 mediates angiotensin II-induced (pro)renin receptor expression in the rat
      renal medulla.
AB  - (Pro)renin receptor (PRR) is predominantly expressed in the distal nephron where
      it is activated by angiotensin II (ANG II), resulting in increased renin activity
      in the renal medulla thereby amplifying the de novo generation and action of
      local ANG II. The goal of the present study was to test the role of cycloxygenase
      2 (COX-2) in meditating ANG II-induced PRR expression in the renal medulla in
      vitro and in vivo. Exposure of primary rat inner medullary collecting duct cells
      to ANG II induced sequential increases in COX-2 and PRR protein expression. When
      the cells were pretreated with a COX-2 inhibitor NS-398, ANG II-induced
      upregulation of PRR protein expression was almost completely abolished, in
      parallel with the changes in medium active renin content. The inhibitory effect
      of NS-398 on the PRR expression was reversed by adding exogenous PGE2. A 14-day
      ANG II infusion elevated renal medullary PRR expression and active and total
      renin content in parallel with increased urinary renin, all of which were
      remarkably suppressed by the COX-2 inhibitor celecoxib. In contrast, plasma and
      renal cortical active and total renin content were suppressed by ANG II
      treatment, an effect that was unaffected by COX-2 inhibition. Systolic blood
      pressure was elevated with ANG II infusion, which was attenuated by the COX-2
      inhibition. Overall, the results obtained from in vitro and in vivo studies
      established a crucial role of COX-2 in mediating upregulation of renal medullary
      PRR expression and renin content during ANG II hypertension. 

PMID- 24740789
TI  - Hemodialysis restored iron distribution that was sequestered in the spleen by
      bilateral nephrectomy.
AB  - Acute kidney injury (AKI) is associated with dysregulated iron metabolism, which
      may play a significant role in cellular injury. The effect of hemodialysis (HD)
      on iron metabolism in AKI therapy has not been well defined. The effects of HD on
      iron parameters were tested in control rats and bilateral nephrectomy (BNx) rats.
      The BNx rats were divided into the following three groups: 1) the sham-operated
      group (BNx-Sham), 2) the BNx group, and 3) the HD group (BNx-HD), which received
      HD therapy 40-45 h after BNx. Sections of the liver or spleen were stained with
      Berlin blue to examine the accumulation of iron. The mRNA levels of hepcidin and
      ferroportin 1 in the spleen and liver were also quantified using RT-PCR. In the
      BNx group, the plasma iron and hematocrit levels were decreased, and hepcidin
      levels were increased. The iron staining in the spleen in the BNx group was
      significantly more intense than that in the BNx-Sham group; however, after an HD
      session, splenic iron staining diminished to the level of the sham group along
      with an increase in plasma iron and a decrease in hepcidin. BNx moved iron from
      hemoglobin and the plasma to the spleen, which is associated with an increase in
      plasma hepcidin. A single HD session accelerated the release of iron from the
      spleen, and the increased plasma iron was linked to the removal of hepcidin. Our
      data suggested that hepcidin might dynamically modulate the iron metabolism in
      BNx as well as in HD.

PMID- 24740790
TI  - Phosphodiesterase 5 inhibition ameliorates angiontensin II-induced podocyte
      dysmotility via the protein kinase G-mediated downregulation of TRPC6 activity.
AB  - The emerging role of the transient receptor potential cation channel isotype 6
      (TRPC6) as a central contributor to various pathological processes affecting
      podocytes has generated interest in the development of therapeutics to modulate
      its function. Recent insights into the regulation of TRPC6 have revealed PKG as a
      potent negative modulator of TRPC6 conductance and associated signaling via its
      phosphorylation at two highly conserved amino acid residues: Thr(69)/Thr(70)
      (Thr(69) in mice and Thr(70) in humans) and Ser(321)/Ser(322) (Ser(321) in mice
      and Ser(322) in humans). Here, we tested the role of PKG in modulating TRPC6
      dependent responses in primary and conditionally immortalized mouse podocytes.
      TRPC6 was phosphorylated at Thr(69) in nonstimulated podocytes, but this declined
      upon ANG II stimulation or overexpression of constitutively active calcineurin
      phosphatase. ANG II induced podocyte motility in an in vitro wound assay, and
      this was reduced 30-60% in cells overexpressing a phosphomimetic mutant TRPC6
      (TRPC6T70E/S322E) or activated PKG (P < 0.05). Pretreatment of podocytes with the
      PKG agonists S-nitroso-N-acetyl-dl-penicillamine (nitric oxide donor), 8-bromo
      cGMP, Bay 41-2772 (soluble guanylate cyclase activator), or phosphodiesterase 5
      (PDE5) inhibitor 4-{[3',4'-(methylenedioxy)benzyl]amino}[7]-6-methoxyquinazoline
      attenuated ANG II-induced Thr(69) dephosphorylation and also inhibited TRPC6
      dependent podocyte motility by 30-60%. These data reveal that PKG activation
      strategies, including PDE5 inhibition, ameliorate ANG II-induced podocyte
      dysmotility by targeting TRPC6 in podocytes, highlighting the potential
      therapeutic utility of these approaches to treat hyperactive TRPC6-dependent
      glomerular disease.

PMID- 24740793
TI  - Ab initio study of TaON, an active photocatalyst under visible light irradiation.
AB  - Tantalum oxynitride has been studied as an active photocatalyst under visible
      light, using a full potential linearized augmented plane wave method within the
      framework of density functional theory. The electronic and optical properties of
      TaON are calculated using local density approximation (LDA), generalized gradient
      approximation (GGA), Engel-Vosko generalized gradient approximation (EVGGA) and
      the modified Becke-Johnson (mBJ) potential approximation to describe the exchange
      correlation potential. The calculated band gap value obtained by the mBJ
      approximation approach (2.5 eV) is very close to the experimental result (2.5
      eV). We found that hybridization among the Ta-d, O-p and N-p states results in
      the formation of a covalent bond between Ta-N and Ta-O. The calculated optical
      properties confirm that the TaON is an active photocatalyst under visible light
      irradiation. TaON has a high dielectric constant and the components show
      anisotropy in the energy range between 3.0 eV and 10.0 eV. A high refractive
      index of 2.47 at 632.8 nm is obtained which shows better agreement with the
      experimental value (2.5 at 632.8 nm) than previous results. 

PMID- 24740791
TI  - Mechanisms of AT1a receptor-mediated uptake of angiotensin II by proximal tubule
      cells: a novel role of the multiligand endocytic receptor megalin.
AB  - The present study tested the hypothesis that the multiligand endocytic receptor
      megalin is partially involved in the uptake of ANG II and downstream signaling
      responses in mouse proximal tubule cells (mPCT) by interacting with AT1a
      receptors. mPCT cells of wild-type (WT) and AT1a receptor-deficient (AT1a-KO)
      mice were treated with vehicle, the AT1 receptor blocker losartan (10 MUM), or a
      selective megalin small interfering (si) RNA for 48 h. The uptake of fluorescein
      (FITC)-labeled ANG II (10 nM, 37 degrees C) and downstream signaling responses
      were analyzed by fluorescence imaging and Western blotting. AT1a receptors and
      megalin were abundantly expressed in mPCT cells, whereas AT1a receptors were
      absent in AT1a-KO mPCT cells (P < 0.01). In WT mPCT cells, FITC-ANG II uptake was
      visualized at 30 min in the cytoplasm and in the nuclei 1 h after exposure.
      Losartan alone completely blocked the uptake of FITC-ANG II, whereas megalin
      siRNA inhibited only 30% of the response (P < 0.01). The remaining FITC-ANG II
      uptake in the presence of megalin siRNA was completely abolished by losartan. ANG
      II induced threefold increases in phosphorylated MAP kinases ERK1/2 and a onefold
      increase in phosphorylated sodium and hydrogen exchanger 3 (NHE3) proteins, which
      were also blocked by losartan and megalin-siRNA. By contrast, losartan and
      megalin siRNA had no effects on these signaling proteins in AT1a-KO mPCT cells.
      We conclude that the uptake of ANG II and downstream MAP kinases ERK1/2 and NHE3
      signaling responses in mPCT cells are mediated primarily by AT1a receptors.
      However, megalin may also play a partial role in these responses to ANG II. 

PMID- 24740792
TI  - Mesangial cell alphavbeta8-integrin regulates glomerular capillary integrity and
      repair.
AB  - alphavbeta8-Integrin is most abundantly expressed in the kidney, brain, and
      female reproductive organs, and its cognate ligand is latent transforming growth
      factor (LTGF)-beta. Kidney alphavbeta8-integrin localizes to mesangial cells, and
      global beta8-integrin gene (Itgb8) deletion results in embryonic lethality due to
      impaired placentation and cerebral hemorrhage. To circumvent the lethality and
      better define kidney alphavbeta8-integrin function, Cre-lox technology was used
      to generate mesangial-specific Itgb8-null mice. Platelet-derived growth factor
      beta receptor (PDGFBR)-Cre mice crossed with a reporter strain revealed
      functional Cre recombinase activity in a predicted mesangial pattern. However,
      mating between two different PDGFBR-Cre or Ren1(d)-Cre strains with Itgb8 (flox/
      ) mice consistently resulted in incomplete recombination, with no renal phenotype
      in mosaic offspring. Induction of a renal phenotype with Habu snake venom, a
      reversible mesangiolytic agent, caused exaggerated glomerular capillary
      microaneurysms and delayed recovery in Cre(+/-) PDGFRB (flox/-) mice compared
      with Cre(+/-) PDGFRB (flox/+) control mice. To establish the mechanism, in vitro
      experiments were conducted in Itgb8-null versus Itgb8-expressing mesangial cells
      and fibroblasts, which revealed beta8-integrin-regulated adhesion to Arg-Gly-Asp
      (RGD) peptides within a mesangial-conditioned matrix as well as beta8-integrin
      dependent migration on RGD-containing LTGF-beta or vitronectin matrices. We
      speculate that kidney alphavbeta8-integrin indirectly controls glomerular
      capillary integrity through mechanical tension generated by binding RGD peptides
      in the mesangial matrix, and healing after glomerular injury may be facilitated
      by mesangial cell migration, which is guided by transient beta8-integrin
      interactions with RGD ligands.

PMID- 24740794
TI  - Solution NMR studies reveal no global flexibility in the catalytic domain of
      CDC25B.
AB  - The CDC25B phosphatase is a critical regulator of the cell cycle and has been
      validated as an important therapeutic target in cancer. Previous studies using
      molecular dynamics simulations have concluded that the catalytic domain of CDC25B
      may experience a significant degree of dynamics or be partially disordered in
      solution, a finding that has a pronounced impact on the structure-based
      development of CDC25B inhibitors. We have probed the backbone dynamics of the
      CDC25B catalytic domain in solution using NMR relaxation experiments and found
      that the core of the protein is relatively rigid and does not experience any
      large-scale dynamics over a broad range of time scales. Furthermore, based on
      residual dipolar coupling measurements we have concluded that the conformation in
      solution is very similar to that observed in the crystal form. Importantly, these
      findings rationalize the application of the CDC25B crystal structure in structure
      based drug development.

PMID- 24740795
TI  - Gold nanoparticles induce nuclear damage in breast cancer cells, which is further
      amplified by hyperthermia.
AB  - Gold nanoparticles have emerged as promising tools for cancer research and
      therapy, where they can promote thermal killing. The molecular mechanisms
      underlying these events are not fully understood. The geometry and size of gold
      nanoparticles can determine the severity of cellular damage. Therefore, small and
      big gold nanospheres as well as gold nanoflowers were evaluated side-by-side. To
      obtain quantitative data at the subcellular and molecular level, we assessed how
      gold nanoparticles, either alone or in combination with mild hyperthermia,
      altered the physiology of cultured human breast cancer cells. Our analyses
      focused on the nucleus, because this organelle is essential for cell survival. We
      showed that all the examined gold nanoparticles associated with nuclei. However,
      their biological effects were quantitatively different. Thus, depending on the
      shape and size, gold nanoparticles changed multiple nuclear parameters. They
      redistributed stress-sensitive regulators of nuclear biology, altered the nuclear
      morphology, reorganized nuclear laminae and envelopes, and inhibited nucleolar
      functions. In particular, gold nanoparticles reduced the de novo biosynthesis of
      RNA in nucleoli, the subnuclear compartments that produce ribosomes. While small
      gold nanospheres and nanoflowers, but not big gold nanospheres, damaged the
      nucleus at normal growth temperature, several of these defects were further
      exacerbated by mild hyperthermia. Taken together, the toxicity of gold
      nanoparticles correlated with changes in nuclear organization and function. These
      results emphasize that the cell nucleus is a prominent target for gold
      nanoparticles of different morphologies. Moreover, we demonstrated that RNA
      synthesis in nucleoli provides quantitative information on nuclear damage and
      cancer cell survival. 

PMID- 24740798
TI  - Measurement of large low-order aberrations by using a series of through-focus
      Ronchigrams.
AB  - A method for measuring large aberrations up to second order (defocus, 2-fold
      astigmatism and axial coma), which uses a through-focus series of Ronchigrams, is
      proposed. The method is based on the principle that line-focus conditions in
      Ronchigrams can be locally detected and low-order aberrations can thereby be
      measured. The proposed method provides auto-tuning of large low-order aberration;
      in particular, iterative aberration measurement and correction reduce low-order
      aberrations from several thousand nanometers to less than a few hundred
      nanometers, which can be handled by conventional fine-aberration tuning methods. 

PMID- 24740796
TI  - The ether lipid precursor hexadecylglycerol protects against Shiga toxins.
AB  - Shiga toxin-producing Escherichia coli bacteria cause hemorrhagic colitis and
      hemolytic uremic syndrome in humans. Currently, only supportive treatment is
      available for diagnosed patients. We show here that 24-h pretreatment with an
      ether lipid precursor, the alkylglycerol sn-1-O-hexadecylglycerol (HG), protects
      HEp-2 cells against Shiga toxin and Shiga toxin 2. Also the endothelial cell
      lines HMEC-1 and HBMEC are protected against Shiga toxins after HG pretreatment.
      In contrast, the corresponding acylglycerol, DL-alpha-palmitin, has no effect on
      Shiga toxicity. Although HG treatment provides a strong protection (~30 times
      higher IC50) against Shiga toxin, only a moderate reduction in toxin binding was
      observed, suggesting that retrograde transport of the toxin from the plasma
      membrane to the cytosol is perturbed. Furthermore, endocytosis of Shiga toxin and
      retrograde sorting from endosomes to the Golgi apparatus remain intact, but
      transport from the Golgi to the endoplasmic reticulum is inhibited by HG
      treatment. As previously described, HG reduces the total level of all quantified
      glycosphingolipids to 50-70% of control, including the Shiga toxin receptor
      globotriaosylceramide (Gb3), in HEp-2 cells. In accordance with this, we find
      that interfering with Gb3 biosynthesis by siRNA-mediated knockdown of Gb3
      synthase for 24 h causes a similar cytotoxic protection and only a moderate
      reduction in toxin binding (to 70% of control cells). Alkylglycerols, including
      HG, have been administered to humans for investigation of therapeutic roles in
      disorders where ether lipid biosynthesis is deficient, as well as in cancer
      therapy. Further studies may reveal if HG can also have a therapeutic potential
      in Shiga toxin-producing E. coli infections.

PMID- 24740799
TI  - Urinary metabolite profiling identifies novel colonic metabolites and conjugates
      of phenolics in healthy volunteers.
AB  - SCOPE: The colonic metabolism of dietary flavonoids, phenolic acids and their
      phenolic metabolites is complex and many metabolites and conjugates have not yet
      been unambiguously identified in humans. METHODS AND RESULTS: Urine samples from
      nine healthy human volunteers obtained after the ingestion of a puree of five
      (poly)phenol-rich berry fruits were analysed using LC-Orbitrap MS to provide a
      preliminary indication of possible metabolites based on exact mass. In most
      cases, the identity of compounds was confirmed using standards produced either
      chemically or enzymically followed by analysis using LC-triple quadrupole MS.
      Sulphated, glucuronidated and methylated forms of catechol, pyrogallol and
      protocatechuic acid mostly appeared in urine after 8 h, suggesting colonic
      metabolism. Gallic acid and (-)-epicatechin conjugates appeared mainly before 4
      h, indicative of absorption from the small intestine. Conjugates of ferulic,
      caffeic, and vanillic acid appeared at intermediate times. CONCLUSION: We have
      positively identified metabolites and conjugates, some novel, in the urine of
      healthy volunteers after intake of multiple phenolics from a mixed puree from
      berry fruits, with each being excreted at specific and signature times. Some of
      these compounds could potentially be used as biomarkers of fruit intake. The
      possible biological activities of these colonic metabolites require further
      assessment.

PMID- 24740800
TI  - News from the IAEH: achieving transdisciplinary ecohealth education in early
      professional development.

PMID- 24740801
TI  - Unjailing of the septal perforator using a rotational atherectomy device prior to
      alcohol septal ablation in a patient with symptomatic hypertrophic obstructive
      cardiomyopathy.
AB  - We report a novel approach in which successful unjailing of the septal perforator
      was performed through the side branch of a coronary stent using a rotational
      atherectomy device for the purpose of alcohol septal ablation in a patient with
      symptomatic hypertrophic obstructive cardiomyopathy.

PMID- 24740802
TI  - Localized plasmon assisted structured illumination microscopy for wide-field high
      speed dispersion-independent super resolution imaging.
AB  - A new super resolution imaging method, i.e. Localized Plasmon assisted Structured
      Illumination Microscopy (LPSIM), is proposed. LPSIM uses an array of localized
      plasmonic antennas to provide dynamically tunable near-field excitations
      resulting in finely structured illumination patterns, independent of any
      propagating surface plasmon dispersion limitations. The illumination pattern
      feature sizes are limited only by the antenna geometry, and a far-field image
      resolved far beyond the diffraction limit is obtained. This approach maintains a
      wide field of view and the capacity for a high frame-rate. The recovered images
      for various classes of objects are presented, demonstrating a significant
      resolution improvement over existing methods. 

PMID- 24740803
TI  - Application of bioflocculating property of Pseudomonas aeruginosa strain IASST201
      in treatment of oil-field formation water.
AB  - A bioflocculating activity of 89.8% was depicted by an activated sludge-borne
      bacteria Pseudomonas aeruginosa strain IASST201 with a yield of bioflocculant of
      2.68 g L(-1) obtained from production media broth after optimization of different
      parameters. The highest bioflocculation efficiency was found at the pre
      stationary phase of the bacterial growth period in the production media broth at
      96th hour examined from a growth-flocculation kinetics study. 85.67% of
      bioflocculation was observed in oil-field formation water, with a separation of
      68.7% of aliphatic hydrocarbon contents of the formation water after the
      application of the bacterial bioflocculant by entrapment mechanism with formation
      of flocs which was analyzed and examined comparatively through gas
      chromatography. Extensive removal of heavy metal contents of the oil-field
      formation water due to bioflocculation was estimated by Atomic Absorption
      Spectrophotometer (AAS). The SEM and AFM studies declare the extracellular
      polymeric nature of the bioflocculant produced by this bacterium clumped within
      bacterial biofilm supported with FTIR study of the extracted bioflocculant.

PMID- 24740804
TI  - Predictive factors of early mortality after transcatheter aortic valve
      implantation: individual risk assessment using a simple score.
AB  - OBJECTIVE: Decision making for intervention in symptomatic aortic stenosis should
      balance the risks of surgery and of transcatheter aortic valve implantation
      (TAVI). We identified the factors associated with early mortality after TAVI and
      aimed to develop and validate a simple risk score. METHODS: A population of 3833
      consecutive patients was randomly split into two cohorts comprising 2552 and 1281
      patients, used respectively to develop and validate a scoring system predicting
      30-day or in-hospital mortality. RESULTS: TAVI was performed using the Edwards
      Sapien prosthesis in 2551 (66.8%) patients and the Medtronic Corevalve in 1270
      (33.2%). Approach was transfemoral in 2801 (73.4%) patients, transapical in 678
      (17.8%), subclavian in 219 (5.7%) and other in 117 (3.1%). Early mortality was
      10.0% (382 patients). A multivariate logistic model identified the following
      predictive factors of early mortality: age >=90 years, body mass index <30
      Kg/m(2), New York Heart Association class IV, pulmonary hypertension, critical
      haemodynamic state, >=2 pulmonary oedemas during the last year, respiratory
      insufficiency, dialysis and transapical or other (transaortic and transcarotid)
      approaches. A 21-point predictive score was derived. C-index was 0.67 for the
      score in the development cohort and 0.59 in the validation cohort. There was a
      good concordance between predicted and observed 30-day mortality rates in the
      development and validation cohorts. CONCLUSIONS: Early mortality after TAVI is
      mainly related to age, the severity of symptoms, comorbidities and transapical
      approach. A simple score can be used to predict early mortality after TAVI. The
      moderate discrimination is however a limitation for the accurate identification
      of high-risk patients.

PMID- 24740805
TI  - Epilepsy: old syndromes, new genes.
AB  - Next-generation sequencing technologies have tremendously increased the speed of
      gene discovery in monogenic epilepsies, enabling us to identify a genetic cause
      in an increasing proportion of patients, and to better understand the underlying
      pathophysiology of their disease. The rapid speed with which new genes are being
      described lately, confronts clinicians with the difficult task of keeping up to
      date with the continuous supply of new publications. This article aims to discuss
      some of the genes that were recently discovered in monogenic familial epilepsy
      syndromes or epileptic encephalopathies for which an underlying cause remained
      unknown for a long time. 

PMID- 24740806
TI  - Understanding essential tremor: progress on the biological front.
AB  - For many years, little was written about the underlying biology of ET, despite
      its high prevalence. Discussions of disease mechanisms were dominated by a focus
      on tremor physiology. The traditional model of ET, the olivary model, was
      proposed in the 1970s. The model suffers from several critical problems, and its
      relevance to ET has been questioned. Recent mechanistic research has focused on
      the cerebellum. Clinical and neuroimaging studies strongly implicate the
      importance of this brain region in ET. Recent mechanistic research has been
      grounded more in tissue-based changes (i.e., postmortem studies of the brain).
      These studies have collectively and systematically identified a sizable number of
      changes in the ET cerebellum, and have led to a new model of ET, referred to as
      the cerebellar degenerative model. Hence, there is a renewed interest in the
      science behind the biology of ET. How the new understanding of ET will translate
      into treatment changes is an open question. 

PMID- 24740808
TI  - Epistemic injustice in healthcare: a philosophial analysis.
AB  - In this paper we argue that ill persons are particularly vulnerable to epistemic
      injustice in the sense articulated by Fricker (Epistemic injustice. Power and the
      ethics of knowing. Oxford University Press, Oxford, 2007). Ill persons are
      vulnerable to testimonial injustice through the presumptive attribution of
      characteristics like cognitive unreliability and emotional instability that
      downgrade the credibility of their testimonies. Ill persons are also vulnerable
      to hermeneutical injustice because many aspects of the experience of illness are
      difficult to understand and communicate and this often owes to gaps in collective
      hermeneutical resources. We then argue that epistemic injustice arises in part
      owing to the epistemic privilege enjoyed by the practitioners and institutions of
      contemporary healthcare services--the former owing to their training, expertise,
      and third-person psychology, and the latter owing to their implicit privileging
      of certain styles of articulating and evidencing testimonies in ways that
      marginalise ill persons. We suggest that a phenomenological toolkit may be part
      of an effort to ameliorate epistemic injustice.

PMID- 24740807
TI  - The use of targeted temperature management for elevated intracranial pressure.
AB  - The use of hypothermia for treatment of intracranial hypertension is
      controversial, despite no other medical therapy demonstrating consistent
      improvements in morbidity or mortality. Much of this may be the result of
      negative results from randomized controlled trials. However, the patients
      selected for these trials may have obscured the results in the populations most
      likely to benefit. Further, brain injury does not behave uniformly, not even
      within a diagnosis. Therefore, therapies may have more benefit in some diseases,
      less in others. This review focuses on the effect on outcome of intracranial
      hypertension in common disease processes in the neurocritical care unit, and
      identifies who is most likely to benefit from the use of hypothermia. 

PMID- 24740810
TI  - TFPI cofactor function of protein S: essential role of the protein S SHBG-like
      domain.
AB  - Protein S is a cofactor for tissue factor pathway inhibitor (TFPI), accelerating
      the inhibition of activated factor X (FXa). TFPI Kunitz domain 3 residue Glu226
      is essential for enhancement of TFPI by protein S. To investigate the
      complementary functional interaction site on protein S, we screened 44 protein S
      point, composite or domain swap variants spanning the whole protein S molecule
      for their TFPI cofactor function using a thrombin generation assay. Of these
      variants, two protein S/growth arrest-specific 6 chimeras, with either the whole
      sex hormone-binding globulin (SHBG)-like domain (Val243-Ser635; chimera III) or
      the SHBG laminin G-type 1 subunit (Ser283-Val459; chimera I), respectively,
      substituted by the corresponding domain in growth arrest-specific 6, were unable
      to enhance TFPI. The importance of the protein S SHBG-like domain (and its
      laminin G-type 1 subunit) for binding and enhancement of TFPI was confirmed in
      FXa inhibition assays and using surface plasmon resonance. In addition, protein S
      bound to C4b binding protein showed greatly reduced enhancement of TFPI-mediated
      inhibition of FXa compared with free protein S. We show that binding of TFPI to
      the protein S SHBG-like domain enables TFPI to interact optimally with FXa on a
      phospholipid membrane. 

PMID- 24740811
TI  - Risk of multiple primary malignancies following treatment of Hodgkin lymphoma.
AB  - We assessed risk, localization, and timing of third malignancies in Hodgkin
      lymphoma (HL) survivors. In a cohort of 3122 5-year HL survivors diagnosed before
      the age of 51 years and treated between 1965 and 1995, we examined whether risk
      factors for second and third malignancies differ and whether the occurrence of a
      second malignancy affects the risk of subsequent malignancies, using recurrent
      event analyses. After a median follow-up of 22.6 years, 832 patients developed a
      second malignancy and 126 patients a third one. The risk of a second malignancy
      was 4.7-fold increased (95% confidence interval [CI], 4.4-5.1) compared with risk
      in the general population; the risk for a third malignancy after a second
      malignancy was 5.4-fold (95% CI, 4.4-6.5) increased. The 10-year cumulative
      incidence of any third malignancy was 13.3%. Compared with patients still free of
      a second malignancy, patients with a second malignancy had a higher risk of
      developing subsequent malignancies. This risk depended on age, with hazard ratios
      of 2.2, 1.6, and 1.1 for patients aged <25, 25 to 34, and 35 to 50 years at HL
      treatment, respectively. In HL survivors who had a second malignancy, treating
      physicians should be aware of the increased risk of subsequent malignancies. 

PMID- 24740812
TI  - Integrated genomic analysis illustrates the central role of JAK-STAT pathway
      activation in myeloproliferative neoplasm pathogenesis.
AB  - Genomic studies have identified somatic alterations in the majority of
      myeloproliferative neoplasms (MPN) patients, including JAK2 mutations in the
      majority of MPN patients and CALR mutations in JAK2-negative MPN patients.
      However, the role of JAK-STAT pathway activation in different MPNs, and in
      patients without JAK2 mutations, has not been definitively delineated. We used
      expression profiling, single nucleotide polymorphism arrays, and mutational
      profiling to investigate a well-characterized cohort of MPN patients. MPN
      patients with homozygous JAK2V617F mutations were characterized by a distinctive
      transcriptional profile. Notably, a transcriptional signature consistent with
      activated JAK2 signaling is seen in all MPN patients regardless of clinical
      phenotype or mutational status. In addition, the activated JAK2 signature was
      present in patients with somatic CALR mutations. Conversely, we identified a gene
      expression signature of CALR mutations; this signature was significantly enriched
      in JAK2-mutant MPN patients consistent with a shared mechanism of transformation
      by JAK2 and CALR mutations. We also identified a transcriptional signature of
      TET2 mutations in MPN patent samples. Our data indicate that MPN patients,
      regardless of diagnosis or JAK2 mutational status, are characterized by a
      distinct gene expression signature with upregulation of JAK-STAT target genes,
      demonstrating the central importance of the JAK-STAT pathway in MPN pathogenesis.

PMID- 24740814
TI  - Dynamic self-assembly of polycationic clusters based on cyclodextrins for pH
      sensitive DNA nanocondensation and delivery by component design.
AB  - The ability of cyclodextrin-based polycationic cluster to undergo reversible DNA
      condensation and release in a physiologically useful pH window has been finely
      tuned by the installation of a capping xylylene moiety at the secondary face of
      the cyclooligosaccharide. This strategy can be exploited advantageously in the
      design of self-assembling nonviral gene-delivery systems from molecular entities.

PMID- 24740813
TI  - CD166 regulates human and murine hematopoietic stem cells and the hematopoietic
      niche.
AB  - We previously showed that immature CD166(+) osteoblasts (OB) promote
      hematopoietic stem cell (HSC) function. Here, we demonstrate that CD166 is a
      functional HSC marker that identifies both murine and human long-term
      repopulating cells. Both murine LSKCD48(-)CD166(+)CD150(+) and LSKCD48(
      )CD166(+)CD150(+)CD9(+) cells, as well as human Lin(-)CD34(+)CD38(
      )CD49f(+)CD166(+) cells sustained significantly higher levels of chimerism in
      primary and secondary recipients than CD166(-) cells. CD166(-/-) knockout (KO)
      LSK cells engrafted poorly in wild-type (WT) recipients and KO bone marrow cells
      failed to radioprotect lethally irradiated WT recipients. CD166(-/-) hosts
      supported short-term, but not long-term WT HSC engraftment, confirming that loss
      of CD166 is detrimental to the competence of the hematopoietic niche. CD166(-/-)
      mice were significantly more sensitive to hematopoietic stress. Marrow-homed
      transplanted WT hematopoietic cells lodged closer to the recipient endosteum than
      CD166(-/-) cells, suggesting that HSC-OB homophilic CD166 interactions are
      critical for HSC engraftment. STAT3 has 3 binding sites on the CD166 promoter and
      STAT3 inhibition reduced CD166 expression, suggesting that both CD166 and STAT3
      may be functionally coupled and involved in HSC competence. These studies
      illustrate the significance of CD166 in the identification and engraftment of HSC
      and in HSC-niche interactions, and suggest that CD166 expression can be modulated
      to enhance HSC function. 

PMID- 24740815
TI  - Alterations in amplitude of low frequency fluctuation in treatment-naive major
      depressive disorder measured with resting-state fMRI.
AB  - There are limited resting-state functional magnetic resonance imaging (fMRI)
      studies in major depressive disorder (MDD). Of these studies, functional
      connectivity analyses are mostly used. However, a new method based on the
      magnitude of low frequency fluctuation (LFF) during resting-state fMRI may
      provide important insight into MDD. In this study, we examined the amplitude of
      LFF (ALFF) within the whole brain during resting-state fMRI in 30 treatment-naive
      MDD subjects and 30 healthy control (HC) subjects. When compared with HC, MDD
      subjects showed increased ALFF in the frontal cortex (including the bilateral
      ventral/dorsal anterior cingulate cortex, orbitofrontal cortex, premotor cortex,
      ventral prefrontal cortex, left dorsal lateral frontal cortex, left superior
      frontal cortex), basal ganglia (including the right putamen and left caudate
      nucleus), left insular cortex, right anterior entorhinal cortex and left inferior
      parietal cortex, together with decreased ALFF in the bilateral occipital cortex,
      cerebellum hemisphere, and right superior temporal cortex. These findings may
      relate to characteristics of MDD, such as excessive self-referential processing
      and deficits in cognitive control of emotional processing, which may contribute
      to the persistent and recurrent nature of the disorder.

PMID- 24740816
TI  - Ending aging in super glassy polymer membranes.
AB  - Aging in super glassy polymers such as poly(trimethylsilylpropyne) (PTMSP),
      poly(4-methyl-2-pentyne) (PMP), and polymers with intrinsic microporosity (PIM-1)
      reduces gas permeabilities and limits their application as gas-separation
      membranes. While super glassy polymers are initially very porous, and ultra
      permeable, they quickly pack into a denser phase becoming less porous and
      permeable. This age-old problem has been solved by adding an ultraporous additive
      that maintains the low density, porous, initial stage of super glassy polymers
      through absorbing a portion of the polymer chains within its pores thereby
      holding the chains in their open position. This result is the first time that
      aging in super glassy polymers is inhibited whilst maintaining enhanced CO2
      permeability for one year and improving CO2/N2 selectivity. This approach could
      allow super glassy polymers to be revisited for commercial application in gas
      separations.

PMID- 24740817
TI  - Regional and local scale modeling of stream temperatures and spatio-temporal
      variation in thermal sensitivities.
AB  - Understanding variation in stream thermal regimes becomes increasingly important
      as the climate changes and aquatic biota approach their thermal limits. We used
      data from paired air and water temperature loggers to develop region-scale and
      stream-specific models of average daily water temperature and to explore thermal
      sensitivities, the slopes of air-water temperature regressions, of mostly
      forested streams across Maryland, USA. The region-scale stream temperature model
      explained nearly 90 % of the variation (root mean square error = 0.957  degrees
      C), with the mostly flat coastal plain streams having significantly higher
      thermal sensitivities than the steeper highlands streams with piedmont streams
      intermediate. Model R (2) for stream-specific models was positively related to a
      stream's thermal sensitivity. Both the regional and the stream-specific air-water
      temperature regression models benefited from including mean daily discharge from
      regional gaging stations, but the degree of improvement declined as a stream's
      thermal sensitivity increased. Although catchment size had no relationship to
      thermal sensitivity, steeper streams or those with greater amounts of forest in
      their upstream watershed were less thermally sensitive. The subset of streams
      with three or more summers of temperature data exhibited a wide range of annual
      variation in thermal sensitivity at a site, with the variation not attributable
      to discharge, precipitation patterns, or physical attributes of streams or their
      watersheds. Our findings are a useful starting point to better understand
      patterns in stream thermal regimes. However, a more spatially and temporally
      comprehensive monitoring network should increase understanding of stream
      temperature variation and its controls as climatic patterns change. 

PMID- 24740809
TI  - Oncogenetics and minimal residual disease are independent outcome predictors in
      adult patients with acute lymphoblastic leukemia.
AB  - With intensified pediatric-like therapy and genetic disease dissection, the field
      of adult acute lymphoblastic leukemia (ALL) has evolved recently. In this new
      context, we aimed to reassess the value of conventional risk factors with regard
      to new genetic alterations and early response to therapy, as assessed by
      immunoglobulin/T-cell receptor minimal residual disease (MRD) levels. The study
      was performed in 423 younger adults with Philadelphia chromosome-negative ALL in
      first remission (265 B-cell precursor [BCP] and 158 T-cell ALL), with cumulative
      incidence of relapse (CIR) as the primary end point. In addition to conventional
      risk factors, the most frequent currently available genetic alterations were
      included in the analysis. A higher specific hazard of relapse was independently
      associated with postinduction MRD level >=10(-4) and unfavorable genetic
      characteristics (ie, MLL gene rearrangement or focal IKZF1 gene deletion in BCP
      ALL and no NOTCH1/FBXW7 mutation and/or N/K-RAS mutation and/or PTEN gene
      alteration in T-cell ALL). These 2 factors allowed definition of a new risk
      classification that is strongly associated with higher CIR and shorter relapse
      free and overall survival. These results indicate that genetic abnormalities are
      important predictors of outcome in adult ALL not fully recapitulated by early
      response to therapy. Patients included in this study were treated in the
      multicenter GRAALL-2003 and GRAALL-2005 trials. Both trials were registered at
      http://www.clinicaltrials.gov as #NCT00222027 and #NCT00327678, respectively. 

PMID- 24740818
TI  - Exogenous fatty acid binding protein 4 promotes human prostate cancer cell
      progression.
AB  - Epidemiologic studies have found that obesity is associated with malignant grade
      and mortality in prostate cancer. Several adipokines have been implicated as
      putative mediating factors between obesity and prostate cancer. Fatty acid
      binding protein 4 (FABP4), a member of the cytoplasmic fatty acid binding protein
      multigene family, was recently identified as a novel adipokine. Although FABP4 is
      released from adipocytes and mean circulating concentrations of FABP4 are linked
      with obesity, effects of exogenous FABP4 on prostate cancer progression are
      unclear. In this study, we examined the effects of exogenous FABP4 on human
      prostate cancer cell progression. FABP4 treatment promoted serum-induced prostate
      cancer cell invasion in vitro. Furthermore, oleic acid promoted prostate cancer
      cell invasion only if FABP4 was present in the medium. These promoting effects
      were reduced by FABP4 inhibitor, which inhibits FABP4 binding to fatty acids.
      Immunostaining for FABP4 showed that exogenous FABP4 was taken up into DU145
      cells in three-dimensional culture. In mice, treatment with FABP4 inhibitor
      reduced the subcutaneous growth and lung metastasis of prostate cancer cells.
      Immunohistochemical analysis showed that the number of apoptotic cells, positive
      for cleaved caspase-3 and cleaved PARP, was increased in subcutaneous tumors of
      FABP4 inhibitor-treated mice, as compared with control mice. These results
      suggest that exogenous FABP4 might promote human prostate cancer cell progression
      by binding with fatty acids. Additionally, exogenous FABP4 activated the PI3K/Akt
      pathway, independently of binding to fatty acids. Thus, FABP4 might be a key
      molecule to understand the mechanisms underlying the obesity-prostate cancer
      progression link.

PMID- 24740820
TI  - Protein nanoparticles for intracellular delivery of therapeutic enzymes.
AB  - The use of enzymes as therapeutics is very promising because of their catalytic
      activity and specificity. However, intracellular delivery of active enzymes is
      challenging due to their low stability and large size. The production of protein
      enzyme nanoparticles was investigated with the goal of developing a protein
      carrier for active enzyme delivery. beta-Galactosidase (beta-gal), an enzyme
      whose deficiency is the cause of some lysosomal storage disorders, was
      incorporated into enhanced green fluorescent protein nanoparticles prepared via
      desolvation. Particle size was found to be sensitive to the type of cross-linker,
      cross-linking time, and the presence of imidazole. The results indicate that beta
      gal activity is highly retained (>70%) after particle fabrication and >85% of
      protein is incorporated in the particles. Protein-enzyme nanoparticles exhibited
      higher internalization in multiple cell lines in vitro, compared with the soluble
      enzyme. Importantly, beta-gal retained its activity following intracellular
      delivery. These data demonstrate that protein nanoparticles are a biocompatible,
      high-efficiency alternative for intracellular delivery of active enzyme
      therapeutics.

PMID- 24740819
TI  - Subjective cognitive failures after stroke in young adults: prevalent but not
      related to cognitive impairment.
AB  - Few studies exist on subjective cognitive failures after a stroke in young adults
      (<=50 years) and their relation to objective cognitive performance is unknown.
      Therefore, we investigated the prevalence of subjective cognitive failures in
      patients with a stroke in young adulthood and their relation with objective
      cognitive impairment. This study is part of the "Follow-Up of Transient ischemic
      attack and stroke patients and Unelucidated Risk factor Evaluation"-study (FUTURE
      study), including patients, aged 18-50 years, admitted to our hospital between
      1980 and 2010 with a first-ever TIA or ischemic stroke. The prevalence of
      subjective cognitive failures in patients was determined and compared with 146
      age- and sex-matched stroke-free controls. The relation of subjective failures
      with objective cognitive performance was investigated with linear and logistic
      regression analysis. 160 patients with a TIA and 277 with an ischemic stroke were
      included. After a mean follow-up of 10.1 (SD 8.3) years, the prevalence of
      subjective memory failures was 86.4% and that of subjective executive failures
      was 67.4% in patients, versus 69.7% (p = 0.008) and 41.4% (p = 0.002) in
      controls. A weak association between subjective memory failures and objective
      immediate (beta -0.12, p = 0.011) and delayed memory performance (beta -0.13, p =
      0.010) was observed in patients. Subjective cognitive failures are prevalent
      after stroke in young adults, but not strongly related to objective cognitive
      impairment. Therefore, extensive neuropsychological assessment is essential for
      determination of objective cognitive impairment. However, it is important that
      subjective cognitive failures are recognized as they may indicate underlying
      psychosocial problems.

PMID- 24740821
TI  - Electron-correlated fragment-molecular-orbital calculations for biomolecular and
      nano systems.
AB  - Recent developments in the fragment molecular orbital (FMO) method for
      theoretical formulation, implementation, and application to nano and biomolecular
      systems are reviewed. The FMO method has enabled ab initio quantum-mechanical
      calculations for large molecular systems such as protein-ligand complexes at a
      reasonable computational cost in a parallelized way. There have been a wealth of
      application outcomes from the FMO method in the fields of biochemistry, medicinal
      chemistry and nanotechnology, in which the electron correlation effects play
      vital roles. With the aid of the advances in high-performance computing, the FMO
      method promises larger, faster, and more accurate simulations of biomolecular and
      related systems, including the descriptions of dynamical behaviors in solvent
      environments. The current status and future prospects of the FMO scheme are
      addressed in these contexts. 

PMID- 24740822
TI  - Intraarticular sprifermin (recombinant human fibroblast growth factor 18) in knee
      osteoarthritis: a randomized, double-blind, placebo-controlled trial.
AB  - OBJECTIVE: To evaluate the efficacy and safety of intraarticular sprifermin
      (recombinant human fibroblast growth factor 18) in the treatment of symptomatic
      knee osteoarthritis (OA). METHODS: The study was a randomized, double-blind,
      placebo-controlled, proof-of-concept trial. Intraarticular sprifermin was
      evaluated at doses of 10 MUg, 30 MUg, and 100 MUg. The primary efficacy end point
      was change in central medial femorotibial compartment cartilage thickness at 6
      months and 12 months as determined using quantitative magnetic resonance imaging
      (qMRI). The primary safety end points were nature, incidence, and severity of
      local and systemic treatment-emergent adverse events (AEs) and acute inflammatory
      reactions, as well as results of laboratory assessments. Secondary end points
      included changes in total and compartment femorotibial cartilage thickness and
      volume as assessed by qMRI, changes in joint space width (JSW) seen on
      radiographs, and pain scores on the Western Ontario and McMaster Universities
      Osteoarthritis Index (WOMAC). RESULTS: One hundred ninety-two patients were
      randomized and evaluated for safety, 180 completed the trial, and 168 were
      evaluated for the primary efficacy end point. We found no statistically
      significant dose response in change in central medial femorotibial compartment
      cartilage thickness. Sprifermin was associated with statistically significant,
      dose-dependent reductions in loss of total and lateral femorotibial cartilage
      thickness and volume and in JSW narrowing in the lateral femorotibial
      compartment. All groups had improved WOMAC pain scores, with statistically
      significantly less improvement at 12 months in patients receiving the 100-MUg
      dose of sprifermin as compared with those receiving placebo. There was no
      significant difference in serious AEs, treatment-emergent AEs, or acute
      inflammatory reactions between sprifermin and placebo groups. CONCLUSION: No
      statistically significant relationship between treatment group and reduction in
      central medial femorotibial compartment cartilage thickness was observed;
      however, prespecified structural secondary end points showed statistically
      significant dose-dependent reductions after sprifermin treatment. Sprifermin was
      not associated with any local or systemic safety concerns.

PMID- 24740823
TI  - Elimination of heparin interference during microarray processing of fresh and
      biobank-archived blood samples.
AB  - In the context of environmental health research, biobank blood samples have
      recently been identified as suitable for high-throughput omics analyses enabling
      the identification of new biomarkers of exposure and disease. However, blood
      samples containing the anti-coagulant heparin could complicate transcriptomic
      analysis because heparin may inhibit RNA polymerase causing inefficient cRNA
      synthesis and fluorophore labelling. We investigated the inhibitory effect of
      heparin and the influence of storage conditions (0 or 3 hr bench times, storage
      at room temperature or -80 degrees C) on fluorophore labelling in heparinized
      fresh human buffy coat and whole blood biobank samples during the mRNA work-up
      protocol for microarray analysis. Subsequently, we removed heparin by lithium
      chloride (LiCl) treatment and performed a quality control analysis of LiCl
      treated biobank sample microarrays to prove their suitability for downstream data
      analysis. Both fresh and biobank samples experienced varying degrees of heparin
      induced inhibition of fluorophore labelling, making most samples unusable for
      microarray analysis. RNA derived from EDTA and citrate blood was not inhibited.
      No effect of bench time was observed but room temperature storage gave slightly
      better results. Strong correlations were observed between original blood sample
      RNA yield and the amount of synthesized cRNA. LiCl treatment restored sample
      quality to normal standards in both fresh and biobank samples and the previously
      identified correlations disappeared. Microarrays hybridized with LiCl-treated
      biobank samples were of excellent quality with no identifiable influence of
      heparin. We conclude that, to obtain high quality results, in most cases heparin
      removal is essential in blood-derived RNA samples intended for microarray
      analysis.

PMID- 24740825
TI  - Implant breast reconstruction and radiation: a multicenter analysis of long-term
      health-related quality of life and satisfaction.
AB  - BACKGROUND: Indications for radiotherapy in breast cancer treatment are
      expanding. Long-term satisfaction and health-related quality of life (HR-QOL),
      important outcomes after alloplastic breast reconstruction and radiation, have
      not been measured in irradiated patients by using a condition-specific, validated
      patient-reported outcomes instrument. The aim was to evaluate patient
      satisfaction and HR-QOL in patients with implant breast reconstruction and
      radiotherapy. METHODS: A multicenter cross-sectional survey of patients who
      underwent implant-based breast reconstruction from three centers in the United
      States and Canada, with and without radiation, was performed. Satisfaction with
      breasts, satisfaction with outcome, psychosocial well-being, sexual well-being,
      and physical well-being outcomes were evaluated using the BREAST-Q((c))
      (Reconstruction Module). Multivariable analysis was performed to evaluate the
      effect of radiotherapy on patient satisfaction with breasts with adjustment by
      patient and treatment characteristics. RESULTS: The response rate was 71 %, with
      633 completed questionnaires returned. Mean follow-up was 3.3 years for
      irradiated patients (n = 219) and 3.7 years for nonirradiated patients (n = 414).
      Patients with radiation had significantly lower satisfaction with breasts (58.3
      vs. 64.0; p < 0.01), satisfaction with outcome (66.8 vs. 71.4; p < 0.01),
      psychosocial well-being (66.7 vs. 70.9; p < 0.01), sexual well-being (47.0 vs.
      52.3; p < 0.01), and physical well-being (71.8 vs. 75.1; p < 0.01) compared with
      nonirradiated patients. Multivariable analysis confirmed the negative effect of
      radiotherapy on satisfaction with breasts (beta = -2.6; p = 0.03) when adjusted
      for patient and treatment factors. CONCLUSIONS: Radiotherapy has a negative
      effect on HR-QOL and satisfaction with breasts in patients with implant
      reconstruction compared with nonirradiated patients. The information provided
      here can inform decision-making and help set appropriate expectations for
      patients undergoing implant breast reconstruction and radiation.

PMID- 24740824
TI  - Teriflunomide and its mechanism of action in multiple sclerosis.
AB  - Treatment of multiple sclerosis (MS) is challenging: disease-modifying treatments
      (DMTs) must both limit unwanted immune responses associated with disease
      initiation and propagation (as T and B lymphocytes are critical cellular
      mediators in the pathophysiology of relapsing MS), and also have minimal adverse
      impact on normal protective immune responses. In this review, we summarize key
      preclinical and clinical data relating to the proposed mechanism of action of the
      recently approved DMT teriflunomide in MS. Teriflunomide selectively and
      reversibly inhibits dihydro-orotate dehydrogenase, a key mitochondrial enzyme in
      the de novo pyrimidine synthesis pathway, leading to a reduction in proliferation
      of activated T and B lymphocytes without causing cell death. Results from animal
      experiments modelling the immune activation implicated in MS demonstrate
      reductions in disease symptoms with teriflunomide treatment, accompanied by
      reduced central nervous system lymphocyte infiltration, reduced axonal loss, and
      preserved neurological functioning. In agreement with the results obtained in
      these model systems, phase 3 clinical trials of teriflunomide in patients with MS
      have consistently shown that teriflunomide provides a therapeutic benefit, and
      importantly, does not cause clinical immune suppression. Taken together, these
      data demonstrate how teriflunomide acts as a selective immune therapy for
      patients with MS. 

PMID- 24740826
TI  - Surgical outcome after neoadjuvant chemotherapy and bevacizumab: results from the
      GeparQuinto study (GBG 44).
AB  - PURPOSE: Bevacizumab, a humanized monoclonal antibody against vascular
      endothelial growth factor, has shown increased pathological complete response
      rates when added to neoadjuvant chemotherapy. In various cancer types,
      bevacizumab treatment was accompanied by an increased risk of bleedings and other
      surgical complications. We assessed associated surgical complications. METHODS:
      In the GeparQuinto trial, 1,948 patients were randomized to receive four cycles
      epirubicin/cyclophosphamide (EC, 90/600 mg/m(2) q3w) followed by four cycles
      docetaxel (D, 100 mg/m(2) q3w) each with (ECB-DB) or without (EC-D) bevacizumab
      (B, 15 mg/kg q3w) concurrent with chemotherapy. Surgery had to be performed not
      earlier than 28 days after the last bevacizumab infusion, but within days 21 and
      35 after the last chemotherapy. RESULTS: In 743 (38.1 %) patients, a surgical
      complication (bleedings, hematomas, necrosis, wound infections, abscess) was
      documented prospectively. Baseline characteristics of the patients were well
      balanced between both arms. The breast-conserving surgery (BCS) rate (N = 502)
      was 69.1 % (EC-D) and 71.9 % (ECB-DB; p = 0.464). The first surgical procedure
      was performed at a median of 29 (EC-D) and 34 days (ECB-DB) after last
      chemotherapy with or without bevacizumab infusion (p < 0.001). Surgical
      complications were documented in 38 (10.9 %; EC-D) and 59 (15.0 %; ECB-DB)
      patients (p = 0.103). Surgical complications were significantly higher after ECD
      DB only in patients treated with BCS (N = 53; p = 0.029) or in those requiring
      repeat surgery in order achieve clear margins (N = 23; p = 0.037) compared to the
      EC-D group. CONCLUSIONS: Addition of bevacizumab to neoadjuvant chemotherapy
      might be associated with an increased risk for surgical complications in patients
      treated with BCS or after repeated surgeries.

PMID- 24740827
TI  - Number of negative lymph nodes is associated with survival in thoracic esophageal
      squamous cell carcinoma patients undergoing three-field lymphadenectomy.
AB  - BACKGROUND: The number of negative lymph nodes (NLNs) can be used for predicting
      clinical outcomes for patients with esophageal carcinoma as it is believed to
      reflect the extent of lymphadenectomy. However, when patients are treated with
      the same surgical procedure, its prognostic value is not clear. METHODS: We
      reviewed the records of 332 patients with thoracic esophageal squamous cell
      carcinoma (ESCC) who underwent three-field lymphadenectomy (3FLND) and had at
      least 15 lymph nodes removed. We used Kaplan-Meier estimates to compute overall
      survival (OS), the log-rank tests to assess the equality of survival rates, and
      Cox regression analyses to evaluate the association between survival and NLN
      count after adjusting for potential confounders. RESULTS: At a median follow-up
      interval of 36 months, the median OS was 47 months and the 5-year survival rate
      was 47.0 %. NLN count was independently associated with OS, and higher numbers of
      NLNs were linked to better OS (hazard ratio [HR] 0.970; 95 % confidence interval
      [CI] 0.955-0.986); the effect did not change after we stratified patients into
      node-negative (HR 0.966; 95 % CI 0.933-1.000) and node-positive (HR 0.973; 95 %
      CI 0.955-0.991) groups. CONCLUSION: The NLN count is an important independent
      prognostic factor for patients with thoracic ESCC treated with 3FLND.

PMID- 24740828
TI  - Basing treatment strategy for non-functional pancreatic neuroendocrine tumors on
      tumor size.
AB  - BACKGROUND: Surgical resection is advocated for all stages of pancreatic
      neuroendocrine tumors (PNETs); whether small PNETs can be managed by observation
      alone is controversial. METHODS: The prognoses of patients with non-functional
      PNET managed by surgical resection or observation alone were retrospectively
      analyzed. In patients who had undergone resection, correlation of pathologically
      assessed tumor extension and grade with tumor size were evaluated. RESULTS:
      Nineteen patients with PNET of median tumor diameters of 12 mm (range 6-38 mm)
      were followed up by observation for 19-162 months. Increase of tumor size >20 %
      occurred in three patients, resulting in 5-year progression-free survival of 83
      %, but no distant metastases occurred. Surgical resection was performed in 71
      patients. Tumor size correlated with the incidence of lymph node or hepatic
      metastases, portal vein invasion, and Ki-67 index. None of the 18 patients with a
      tumor size <=15 mm developed lymph node or distant metastases, and all these
      patients survived without recurrence for 5-283 months. The smallest tumor size
      with lymph node metastases was 19 mm. The 5-year recurrence-free survivals of
      patients with a tumor size <=15 mm (100 %) was significantly better than patients
      with tumor sizes 16-20 mm (86 %), 21-30 mm (71 %), 31-50 mm (83 %), and >50 mm
      (48 %). CONCLUSION: Because PNETs <=15 mm in size have little risk of metastases
      or recurrence, careful observation with serial image studies is acceptable. Once
      the tumor size exceeds 15 mm, the risk of metastases and recurrence increases
      significantly.

PMID- 24740829
TI  - Reprogramming using microRNA-302 improves drug sensitivity in hepatocellular
      carcinoma cells.
AB  - BACKGROUND: Although studies have shown that Oct4, Sox2, Klf4, and c-Myc (OKSM)
      mediated induced pluripotent stem cell (iPSC) technology sensitizes cancer cells
      to drugs, the potential risk of inserting c-Myc and random insertions of
      exogenous sequences into the genome persists. Several authors, including us, have
      presented microRNA (miRNA)-mediated reprogramming as an alternative approach.
      Herein, we evaluated the efficacy of miRNA-mediated reprogramming on
      hepatocellular carcinoma (HCC) cells. METHODS: Among three miRNAs (miR-200c, miR
      302s, and miR-369s) that were previously presented for miRNA-mediated
      reprogramming, miR-302 was expressed at low levels in HCC cells. After
      transfecting three times with miR-302, the cells were incubated in ES medium for
      3 weeks and then characterized. RESULTS: iPSC-like spheres were obtained after
      the 3-week incubation. Spheres presented high NANOG and OCT4 expression, low
      proliferation, high apoptosis, low epithelial-mesenchymal transition marker
      expression (N-cadherin, TGFBR2), and sensitization to drugs. Several miRNAs were
      changed (e.g., low oncomiR miR-21, high miR-29b). cMyc was decreased, and
      methylation was elevated on histone 3 at lysine 4 (H3K4). Differentiated cells
      expressed markers of each germ layer (GFAP, FABP4, and ALB). AOF2 (also known as
      LSD1 or KDM1), one of the targets for miR-302, was repressed in iPSC-like
      spheres. Silencing of AOF2 resulted in similar features of iPSC-like-spheres,
      including cMyc down-regulation and H3K4 methylation. In drug-resistant cells,
      sensitization was achieved through miR-302-mediated reprogramming. CONCLUSIONS:
      miR-302-mediated iPSC technology reprogrammed HCC cells and improved drug
      sensitivity through AOF2 down-regulation, which caused H3K4 methylation and c-Myc
      repression.

PMID- 24740830
TI  - Shear wave elastography in evaluation of cervical lymph node metastasis of
      papillary thyroid carcinoma: elasticity index as a prognostic implication.
AB  - PURPOSE: The aim of this study was to evaluate the usefulness of shear wave
      elastography (SWE) for predicting cervical lymph node (LN) metastasis and the
      prognostic implication of SWE as histopathologic factors of papillary thyroid
      carcinoma (PTC). METHODS: Eighty-four LNs of 66 patients with PTC underwent B
      mode ultrasonography (BUS) and SWE before ultrasound-guided fine-needle
      aspiration biopsy or preoperative evaluation. SWE elasticity indices (EI) of mean
      (Emean), minimum (Emin), maximum (Emax) and the ratio of Emean in LNs and
      surrounding muscle (Emean-m) were measured at the stiffest portion of LNs (kPa).
      SWE EI were correlated with the pathologic diagnosis and the histopathologic
      findings, including number and size of metastatic LNs, the ratio of the number of
      metastatic LN/dissected LN, and the presence of extranodal extension. Diagnostic
      performances of SWE EI and BUS for predicting LN metastasis were assessed using
      receiver operating curve analysis. RESULTS: All SWE EI were significantly higher
      in metastatic LNs than in benign LNs (p < 0.005). Combined Emean [area under the
      curve (AUC) 0.811] or Emin (AUC 0.812) with BUS showed significantly higher AUC
      than BUS (0.738) for predicting metastatic LNs (p = 0.041 and 0.033,
      respectively). The number of positive LNs/dissected LNs and the largest LN size
      were significantly correlated with SWE EI (p < 0.05 and p < 0.005, respectively).
      Metastatic LNs with extranodal extension showed significantly higher SWE EI (p <
      0.005) than those without extranodal extension. CONCLUSIONS: Combined use of SWE
      and BUS was adjunctive to the diagnostic performance of BUS for the prediction of
      LN metastasis of PTC, and quantitative SWE could predict pathologic prognostic
      factors of LN metastasis of PTC.

PMID- 24740831
TI  - The molecular mechanisms underpinning the therapeutic properties of oleanolic
      acid, its isomer and derivatives for type 2 diabetes and associated
      complications.
AB  - Recent research has uncovered the molecular mechanisms responsible for the
      therapeutic properties of oleanolic acid (OA), its isomer ursolic acid (UA), and
      derivatives. In particular, recent reports have highlighted the benefits of these
      compounds in the prevention and treatment of type 2 diabetes and associated life
      threatening complications, such as nonalcoholic fatty liver disease, nephropathy,
      retinopathy, and atherosclerosis. The prevalence of type 2 diabetes is of major
      concern since it is reaching global epidemic levels. Treatments targeting the
      signaling pathways altered in type 2 diabetes are being actively investigated,
      and OA and UA in natural and derivative forms are potential candidates to
      modulate these pathways. We will explore the findings from in vitro and in vivo
      studies showing that these compounds: (i) improve insulin signaling and reduce
      hyperglycemia; (ii) reduce oxidative stress by upregulating anti-oxidants and;
      (iii) reduce inflammation by inhibiting proinflammatory signaling. We will
      discuss the molecular mechanisms underpinning these therapeutic properties in
      this review in order to provide a rationale for the future use of OA, UA, and
      their derivatives for the prevention and treatment of type 2 diabetes and
      associated comorbidities. 

PMID- 24740832
TI  - Ba2[Pd(HS2O7)2(S3O10)2]: a heteroleptic polysulfatopalladate.
AB  - The oxidation of elemental palladium with oleum (65 % SO3) in the presence of
      barium carbonate in torch-sealed glass ampoules at 180  degrees C leads to yellow
      single crystals of the heteroleptic palladate Ba2[Pd(HS2O7)2(S3O10)2] (triclinic,
      P1; Z=1; a=884.18(3), b=927.68(3), c=938.77(4) pm; alpha=60.473(1),
      beta=80.266(2), gamma=87.746(2) degrees ). The crystal structure shows the Pd(2+)
      ions in a square-planar coordination of oxygen atoms of two hydrogendisulfate as
      well as of two trisulfate anions. The compound is the first example of the rarely
      seen S3O10(2-) and HS2O7(-) anions acting as ligands in a complex anion and,
      moreover, the first heteroleptic polysulfatometallate known so far. The complex
      formation leads to a stabilization of the trisulfate anion relative to its
      uncoordinated congener. Ba2[Pd(HS2O7)2(S3O10)2] has been further characterized by
      vibrational spectroscopy and quantum chemical calculations. Thermal analyses by
      means of thermogravimetric/differential thermal analysis (TG/DTA) measurements
      show that the compound decomposes to yield elemental palladium and BaSO4.

PMID- 24740833
TI  - A hierarchical method for whole-brain connectivity-based parcellation.
AB  - In modern neuroscience there is general agreement that brain function relies on
      networks and that connectivity is therefore of paramount importance for brain
      function. Accordingly, the delineation of functional brain areas on the basis of
      diffusion magnetic resonance imaging (dMRI) and tractography may lead to highly
      relevant brain maps. Existing methods typically aim to find a predefined number
      of areas and/or are limited to small regions of grey matter. However, it is in
      general not likely that a single parcellation dividing the brain into a finite
      number of areas is an adequate representation of the function-anatomical
      organization of the brain. In this work, we propose hierarchical clustering as a
      solution to overcome these limitations and achieve whole-brain parcellation. We
      demonstrate that this method encodes the information of the underlying structure
      at all granularity levels in a hierarchical tree or dendrogram. We develop an
      optimal tree building and processing pipeline that reduces the complexity of the
      tree with minimal information loss. We show how these trees can be used to
      compare the similarity structure of different subjects or recordings and how to
      extract parcellations from them. Our novel approach yields a more exhaustive
      representation of the real underlying structure and successfully tackles the
      challenge of whole-brain parcellation.

PMID- 24740834
TI  - Prevalence and impact of preoperative moderate/severe tricuspid regurgitation on
      patients undergoing transcatheter aortic valve replacement.
AB  - OBJECTIVES: Significant tricuspid regurgitation (TR) is a marker for late-stage
      myocardial and valvular heart disease. Whether preoperative TR affects clinical
      outcomes of patients undergoing transcatheter aortic valve replacement (TAVR) has
      never been investigated. This study sought to identify the impact of moderate and
      severe TR on outcomes after TAVR. METHODS: All patients undergoing TAVR from
      January 2007 to August 2012 at St. Paul's Hospital, Vancouver, Canada, (n = 518)
      were dichotomized according to the severity of preoperative TR (moderate/severe
      vs. none/mild). All clinical outcomes were defined according to the valve
      academic research consortium-2 definitions. RESULTS: At baseline, moderate or
      severe TR was reported in 79 patients (15.2%). At 30 days, moderate/severe TR had
      improved in 12 patients (15.2%), was unchanged in 46 patients (58.3%), and
      worsened in 7 patients (8.9%). Of those with none/mild TR at baseline, 35 (7.9%)
      patients had moderate TR at 30-day follow-up. Two-year all-cause (38.4% vs.
      20.0%, Log-rank test, P = 0.001) and cardiac mortality (12.9% vs. 4.6%, Log-rank
      test, P = 0.004) as estimated by Kaplan-Meier analysis were considerably higher
      in patients with significant TR. However, significant TR did not emerge as
      independent risk factor for 2-year all-cause mortality (adjusted OR: 1.55, 95%
      confidence interval (CI): 0.91-2.64, P = 0.105). Pre-specified subgroups showed
      an interaction between TR and left ventricular systolic function (Pinteraction  =
      0.047). Indeed, moderate/severe TR was significantly related to mortality only in
      patients with left ventricular ejection fraction (LVEF) > 40% (adjusted OR: 2.01,
      CI: 1.05-3.84, P = 0.036). In patients with LVEF <= 40%, TR had no significant
      impact on all-cause mortality (adjusted OR: 1.04, CI: 0.34-3.16, P = 0.946). No
      significant interactions were identified regarding patients with perioperative
      moderate/severe mitral regurgitation (Pinteraction  = 0.829) and patients with
      baseline systolic pulmonary artery pressure >= 60 mm Hg (Pinteraction  = 0.669).
      CONCLUSIONS: In patients undergoing TAVR, significant preoperative TR was present
      in 15% of patients and associated with more comorbidities. Despite being
      associated with a doubling of mortality rate, after a robust adjustment,
      significant TR was not an independent predictor of 2-year mortality. However, a
      significant interaction between TR and left ventricular systolic function was
      found. The response of TR to TAVR was extremely variable.

PMID- 24740835
TI  - The in vitro estrogenic activities of triclosan and triclocarban.
AB  - Triclosan (TCS) and triclocarban (TCC), as broad spectrum antibacterial agents,
      are distributed widely in the environment and humans. Most studies have focused
      on their distribution and biodegradation, but the endocrine-disrupting effects of
      these chemicals, especially their estrogenic effects, are still unclear. In the
      present study, we investigated the estrogenic effects of TCS and TCC using a
      series of in vitro assays, including the ER reporter gene assay in the CV-1
      cells, E-screen assay and evaluation of estrogen-responsive genes in the MCF-7
      cells. The tested concentrations of TCS and TCC were both from 1 * 10(-9) to 1 *
      10(-6)  M. Results showed that TCS and TCC exerted estrogenic activities by
      inducing luciferase activities in an ER reporter gene assay, promoting the
      proliferation of the MCF-7 cells, up-regulating the expression of pS2 and down
      regulating ERalpha expression at both the mRNA and protein levels in the MCF-7
      cells. We further found that TCS and TCC could alter the expression of multiple
      microRNAs (mir-22, mir-206 and mir-193b) in the MCF-7 cells, which would help
      understand the mechanisms of their estrogenic effects on regulating the
      expression of ERalpha. In brief, our results demonstrated the potential
      estrogenic effects and profiled in vitro data for further risk assessment of TCS
      and TCC.

PMID- 24740836
TI  - Direct catalytic asymmetric vinylogous conjugate addition of unsaturated
      butyrolactones to alpha,beta-unsaturated thioamides.
AB  - Soft Lewis acid/Bronsted base cooperative catalysts have enabled direct catalytic
      asymmetric vinylogous conjugate addition of alpha,beta- and beta,gamma
      unsaturated butyrolactones to alpha,beta-unsaturated thioamides with perfect atom
      economy. When using alpha-angelica lactone and its derivatives as
      pronucleophiles, as little as 0.5 mol% catalyst loading was sufficient to
      complete the reaction necessary to construct consecutive tri- and
      tetrasubstituted stereogenic centers in a highly diastereo- and enantioselective
      fashion.

PMID- 24740837
TI  - What influences youth to operate all-terrain vehicles safely?
AB  - The operation of all-terrain vehicles (ATVs) by youth has contributed to the
      incidence of serious and fatal injuries among children. This study explored
      factors related to the frequency with which youth wore a helmet and refrained
      from engaging in three risky driving behaviors (driving at risky speeds, on paved
      roads and on unfamiliar terrain) while operating an ATV. Youth (n = 248) aged 9
      14 from central Ohio and one of their parents completed self-report measures of
      ATV safety behaviors, youth general propensity for risk taking, protection
      motivation and parental behaviors to facilitate youth safety. Data from two focus
      groups provided insight on quantitative results. Analyses revealed considerable
      variation in the frequency with which youth performed the safety behaviors, with
      13- and 14-year-olds reporting less frequent safe behavior than 9- to 12-year
      olds. Multiple regression analyses suggested that parental behaviors, such as
      providing reminders to wear a helmet, were associated with more frequent helmet
      use but were not associated with risky driving behaviors. Youth's general
      propensity toward risk taking was not associated with helmet use and only
      associated with riskydriving behaviors among the 13- and 14-year-olds. Self
      efficacy was an important predictor across both age groups and behaviors.
      Implications for injury prevention are discussed. 

PMID- 24740838
TI  - An organized approach to complex ethical cases on a surgical service.

PMID- 24740839
TI  - Trust asks High Court to advise on advance decision of patient held under Mental
      Health Act.

PMID- 24740840
TI  - Physical stability comparisons of IgG1-Fc variants: effects of N-glycosylation
      site occupancy and Asp/Gln residues at site Asn 297.
AB  - The structural integrity and conformational stability of various IgG1-Fc proteins
      produced from the yeast Pichia pastoris with different glycosylation site
      occupancy (di-, mono-, and nonglycosylated) were determined. In addition, the
      physical stability profiles of three different forms of nonglycosylated Fc
      molecules (varying amino-acid residues at site 297 in the CH 2 domain due to the
      point mutations and enzymatic digestion of the Fc glycoforms) were also examined.
      The physical stability of these IgG1-Fc glycoproteins was examined as a function
      of pH and temperature by high-throughput biophysical analysis using multiple
      techniques combined with data visualization tools (three index empirical phase
      diagrams and radar charts). Across the pH range of 4.0-6.0, the di- and
      monoglycosylated forms of the IgG1-Fc showed the highest and lowest levels of
      physical stability, respectively, with the nonglycosylated forms showing
      intermediate stability depending on solution pH. In the aglycosylated Fc
      proteins, the introduction of Asp (D) residues at site 297 (QQ vs. DN vs. DD
      forms) resulted in more subtle changes in structural integrity and physical
      stability depending on solution pH. The utility of evaluating the conformational
      stability profile differences between the various IgG1-Fc glycoproteins is
      discussed in the context of analytical comparability studies.

PMID- 24740842
TI  - Genetic variants in microRNAs and microRNA target sites predict biochemical
      recurrence after radical prostatectomy in localized prostate cancer.
AB  - Recent evidence indicates that microRNAs might participate in prostate cancer
      initiation, progression and treatment response. Germline variations in microRNAs
      might alter target gene expression and modify the efficacy of prostate cancer
      therapy. To determine whether genetic variants in microRNAs and microRNA target
      sites are associated with the risk of biochemical recurrence (BCR) after radical
      prostatectomy (RP). We retrospectively studied two independent cohorts composed
      of 320 Asian and 526 Caucasian men with pathologically organ-confined prostate
      cancer who had a median follow-up of 54.7 and 88.8 months after RP, respectively.
      Patients were systematically genotyped for 64 single-nucleotide polymorphisms
      (SNPs) in microRNAs and microRNA target sites, and their prognostic significance
      on BCR was assessed by Kaplan-Meier analysis and Cox regression model. After
      adjusting for known clinicopathologic risk factors, two SNPs (MIR605 rs2043556
      and CDON rs3737336) remained associated with BCR. The numbers of risk alleles
      showed a cumulative effect on BCR [perallele hazard ratio (HR) 1.60, 95%
      confidence interval (CI) 1.16-2.21, p for trend = 0.005] in Asian cohort, and the
      risk was replicated in Caucasian cohort (HR 1.55, 95% CI 1.15-2.08, p for trend =
      0.004) and in combined analysis (HR 1.57, 95% CI 1.26-1.96, p for trend <0.001).
      Results warrant replication in larger cohorts. This is the first study
      demonstrating that SNPs in microRNAs and microRNA target sites can be predictive
      biomarkers for BCR after RP.

PMID- 24740843
TI  - Thiocolchicoside and alcohol abstinence: a case report.

PMID- 24740844
TI  - Do UK television alcohol advertisements abide by the code of broadcast
      advertising rules regarding the portrayal of alcohol?
AB  - AIMS: The aim of the study was to assess the extent to which members of the UK
      general public perceive television alcohol advertisements to comply with the
      regulatory code governing these: the Advertising Standards Authority Code of
      Broadcast Advertising (BCAP Code). The Code provides a general principle and 16
      rules to prevent such adverts implying, condoning or encouraging immoderate,
      irresponsible or anti-social drinking. METHODS: Quota sample of 373 adults,
      representative of the UK population aged 18-74 years in terms of age and gender,
      were recruited at a train station. Participants were shown one of seven
      advertisements that had been broadcast in the previous month on the two leading
      commercial television channels, and then completed a questionnaire with 40
      statements representing the BCAP Code rules. RESULTS: Overall, 75% of the
      participants rated the advertisements as breaching at least one rule from the
      BCAP Code. Breaches were observed for all the seven advertisements, ranging from
      49 to 91% non-compliant. Rules regarding alcohol being presented as contributing
      to popularity or confidence, and implying that alcohol is capable of changing
      mood, physical condition, behaviour, or as nourishment, were seen as being
      breached by over 50% of participants. CONCLUSIONS: A clear majority of the UK
      general public perceive alcohol advertisements to breach the BCAP Code,
      suggesting that the current regulatory system for UK television alcohol
      advertisements is inadequate.

PMID- 24740845
TI  - Content analysis of newspaper reports on alcohol-related deaths.
AB  - AIM: International research indicates that the role which alcohol plays in
      accidents tends to be understated in media reports. Evidence suggests that public
      support for alcohol harm reduction policies would increase if people were better
      informed about the role of alcohol in serious injuries. We hypothesized that the
      role of alcohol in Irish accidental deaths is under-reported in the Irish print
      media. METHOD: We identified all traumatic and poisoning deaths (excluding
      suicides) in Ireland during the years 2008 and 2009 where alcohol was mentioned
      on the death certificate. We conducted an Internet-based search for newspaper
      reports of these deaths. The content of each report was examined and rated for
      mention of alcohol's possible role in the individual death. RESULTS: This study
      demonstrates the under-reporting in Irish newspapers of the role of alcohol in
      traumatic and poisoning deaths. Where deaths were reported, the role played by
      alcohol was generally ignored. CONCLUSION: This represents a missed opportunity
      to inform the public about the role of alcohol in these deaths. More accurate
      information would permit the public to make more informed decisions regarding
      their own behaviour and regarding their support for alcohol harm-reducing
      strategies.

PMID- 24740846
TI  - How accurate are blood (or breath) tests for identifying self-reported heavy
      drinking among people with alcohol dependence?
AB  - AIMS: Managing patients with alcohol dependence includes assessment for heavy
      drinking, typically by asking patients. Some recommend biomarkers to detect heavy
      drinking but evidence of accuracy is limited. METHODS: Among people with
      dependence, we assessed the performance of disialo-carbohydrate-deficient
      transferrin (%dCDT, >=1.7%), gamma-glutamyltransferase (GGT, >=66 U/l), either
      %dCDT or GGT positive, and breath alcohol (> 0) for identifying 3 self-reported
      heavy drinking levels: any heavy drinking (>=4 drinks/day or >7 drinks/week for
      women, >=5 drinks/day or >14 drinks/week for men), recurrent (>=5 drinks/day on
      >=5 days) and persistent heavy drinking (>=5 drinks/day on >=7 consecutive days).
      Subjects (n = 402) with dependence and current heavy drinking were referred to
      primary care and assessed 6 months later with biomarkers and validated self
      reported calendar method assessment of past 30-day alcohol use. RESULTS: The self
      reported prevalence of any, recurrent and persistent heavy drinking was 54, 34
      and 17%. Sensitivity of %dCDT for detecting any, recurrent and persistent self
      reported heavy drinking was 41, 53 and 66%. Specificity was 96, 90 and 84%,
      respectively. %dCDT had higher sensitivity than GGT and breath test for each
      alcohol use level but was not adequately sensitive to detect heavy drinking
      (missing 34-59% of the cases). Either %dCDT or GGT positive improved sensitivity
      but not to satisfactory levels, and specificity decreased. Neither a breath test
      nor GGT was sufficiently sensitive (both tests missed 70-80% of cases).
      CONCLUSIONS: Although biomarkers may provide some useful information, their
      sensitivity is low the incremental value over self-report in clinical settings is
      questionable.

PMID- 24740848
TI  - Aortic root rupture after TAVR in two renal transplant patients on chronic
      immunosuppressant therapy.
AB  - Patients on chronic immunosuppressant therapy after renal transplantation have a
      high rate of in-hospital mortality and approximately 20% mortality rate per year
      after conventional valve surgery. While transcatheter aortic valve replacement
      (TAVR) is an appealing option to consider for such patients, there are not
      significant outcome data for the procedure in this patient population. We report
      two cases of aortic root rupture after TAVR in renal transplant patients on
      chronic immunosuppressant therapy.

PMID- 24740847
TI  - Voltage-gated sodium channel Nav 1.5 contributes to astrogliosis in an in vitro
      model of glial injury via reverse Na+ /Ca2+ exchange.
AB  - Astrogliosis is a prominent feature of many, if not all, pathologies of the brain
      and spinal cord, yet a detailed understanding of the underlying molecular
      pathways involved in the transformation from quiescent to reactive astrocyte
      remains elusive. We investigated the contribution of voltage-gated sodium
      channels to astrogliosis in an in vitro model of mechanical injury to astrocytes.
      Previous studies have shown that a scratch injury to astrocytes invokes dual
      mechanisms of migration and proliferation in these cells. Our results demonstrate
      that wound closure after mechanical injury, involving both migration and
      proliferation, is attenuated by pharmacological treatment with tetrodotoxin (TTX)
      and KB-R7943, at a dose that blocks reverse mode of the Na(+) /Ca(2+) exchanger
      (NCX), and by knockdown of Nav 1.5 mRNA. We also show that astrocytes display a
      robust [Ca(2+) ]i transient after mechanical injury and demonstrate that this
      [Ca(2+) ]i response is also attenuated by TTX, KB-R7943, and Nav 1.5 mRNA
      knockdown. Our results suggest that Nav 1.5 and NCX are potential targets for
      modulation of astrogliosis after injury via their effect on [Ca(2+) ]i .

PMID- 24740849
TI  - Polymer powder processing of cryomilled polycaprolactone for solvent-free
      generation of homogeneous bioactive tissue engineering scaffolds.
AB  - Synthetic polymers used in tissue engineering require functionalization with
      bioactive molecules to elicit specific physiological reactions. These additives
      must be homogeneously dispersed in order to achieve enhanced composite mechanical
      performance and uniform cellular response. This work demonstrates the use of a
      solvent-free powder processing technique to form osteoinductive scaffolds from
      cryomilled polycaprolactone (PCL) and tricalcium phosphate (TCP). Cryomilling is
      performed to achieve micrometer-sized distribution of PCL and reduce melt
      viscosity, thus improving TCP distribution and improving structural integrity. A
      breakthrough is achieved in the successful fabrication of 70 weight percentage of
      TCP into a continuous film structure. Following compaction and melting, PCL/TCP
      composite scaffolds are found to display uniform distribution of TCP throughout
      the PCL matrix regardless of composition. Homogeneous spatial distribution is
      also achieved in fabricated 3D scaffolds. When seeded onto powder-processed
      PCL/TCP films, mesenchymal stem cells are found to undergo robust and uniform
      osteogenic differentiation, indicating the potential application of this approach
      to biofunctionalize scaffolds for tissue engineering applications. 

PMID- 24740850
TI  - Preface to topic "International collaboration to control cholangiocarcinoma".

PMID- 24740851
TI  - Highlights of topic "Etiology and epidemiology of cholangiocarcinoma".

PMID- 24740852
TI  - A novel spatiotemporal analysis of peri-ictal spiking to probe the relation of
      spikes and seizures in epilepsy.
AB  - The relation between epileptic spikes and seizures is an important but still
      unresolved question in epilepsy research. Preclinical and clinical studies have
      produced inconclusive results on the causality or even on the existence of such a
      relation. We set to investigate this relation taking in consideration seizure
      severity and spatial extent of spike rate. We developed a novel automated spike
      detection algorithm based on morphological filtering techniques and then tested
      the hypothesis that there is a pre-ictal increase and post-ictal decrease of the
      spatial extent of spike rate. Peri-ictal (around seizures) spikes were detected
      from intracranial EEG recordings in 5 patients with temporal lobe epilepsy. The
      94 recorded seizures were classified into two classes, based on the percentage of
      brain sites having higher or lower rate of spikes in the pre-ictal compared to
      post-ictal periods, with a classification accuracy of 87.4%. This seizure
      classification showed that seizures with increased pre-ictal spike rate and
      spatial extent compared to the post-ictal period were mostly (83%) clinical
      seizures, whereas no such statistically significant (alpha = 0.05) increase was
      observed peri-ictally in 93% of sub-clinical seizures. These consistent across
      patients results show the existence of a causal relation between spikes and
      clinical seizures, and imply resetting of the preceding spiking process by
      clinical seizures. 

PMID- 24740853
TI  - Unravelling secondary structure changes on individual anionic polysaccharide
      chains by atomic force microscopy.
AB  - The structural conformations of the anionic carrageenan polysaccharides in the
      presence of monovalent salt close to physiological conditions are studied by
      atomic force microscopy. Iota-carrageenan undergoes a coil-helix transition at
      high ionic strength, whereas lambda-carrageenan remains in the coiled state.
      Polymer statistical analysis reveals an increase in persistence length from
      22.6+/-0.2 nm in the random coil, to 26.4+/-0.2 nm in the ordered helical
      conformation, indicating an increased rigidity of the helical iota-carrageenan
      chains. The many decades-long debated issue on whether the ordered state can
      exist as single or double helix, is conclusively resolved by demonstrating the
      existence of a unimeric helix formed intramolecularly by a single polymer chain. 

PMID- 24740854
TI  - Cellular mechanisms for response heterogeneity among L2/3 pyramidal cells in
      whisker somatosensory cortex.
AB  - Whisker deflection evokes sparse, low-probability spiking among L2/3 pyramidal
      cells in rodent somatosensory cortex (S1), with spiking distributed nonuniformly
      between more and less responsive cells. The cellular and local circuit factors
      that determine whisker responsiveness across neurons are unclear. To identify
      these factors, we used two-photon calcium imaging and loose-seal recording to
      identify more and less responsive L2/3 neurons in S1 slices in vitro, during
      feedforward recruitment of the L2/3 network by L4 stimulation. We observed a
      broad gradient of spike recruitment thresholds within local L2/3 populations,
      with low- and high-threshold cells intermixed. This recruitment gradient was
      significantly correlated across different L4 stimulation sites, and between L4
      evoked and whisker-evoked responses in vivo, indicating that a substantial
      component of responsiveness is independent of tuning to specific feedforward
      inputs. Low- and high-threshold L2/3 pyramidal cells differed in L4-evoked
      excitatory synaptic conductance and intrinsic excitability, including spike
      threshold and the likelihood of doublet spike bursts. A gradient of intrinsic
      excitability was observed across neurons. Cells that spiked most readily to L4
      stimulation received the most synaptic excitation but had the lowest intrinsic
      excitability. Low- and high-threshold cells did not differ in dendritic
      morphology, passive membrane properties, or L4-evoked inhibitory conductance.
      Thus multiple gradients of physiological properties exist across L2/3 pyramidal
      cells, with excitatory synaptic input strength best predicting overall spiking
      responsiveness during network recruitment. 

PMID- 24740855
TI  - A potentially novel nicotinic receptor in Aplysia neuroendocrine cells.
AB  - Nicotinic receptors form a diverse group of ligand-gated ionotropic receptors
      with roles in both synaptic transmission and the control of excitability. In the
      bag cell neurons of Aplysia, acetylcholine activates an ionotropic receptor,
      which passes inward current to produce a long-lasting afterdischarge and hormone
      release, leading to reproduction. While testing the agonist profile of the
      cholinergic response, we observed a second current that appeared to be gated only
      by nicotine and not acetylcholine. The peak nicotine-evoked current was markedly
      smaller in magnitude than the acetylcholine-induced current, cooperative (Hill
      value of 2.7), had an EC50 near 500 MUM, readily recovered from desensitization,
      showed Ca(2+) permeability, and was blocked by mecamylamine, dihydro-beta
      erythroidine, or strychnine, but not by alpha-conotoxin ImI, methyllycaconitine,
      or hexamethonium. Aplysia transcriptome analysis followed by PCR yielded 20 full
      length potential nicotinic receptor subunits. Sixteen of these were predicted to
      be cation selective, and real-time PCR suggested that 15 of the 16 subunits were
      expressed to varying degrees in the bag cell neurons. The acetylcholine-induced
      current, but not the nicotine current, was reduced by double-strand RNA treatment
      targeted to both subunits ApAChR-C and -E. Conversely, the nicotine-evoked
      current, but not the acetylcholine current, was lessened by targeting both
      subunits ApAChR-H and -P. To the best of our knowledge, this is the first report
      suggesting that a nicotinic receptor is not gated by acetylcholine. Separate
      receptors may serve as a means to differentially trigger plasticity or safeguard
      propagation by assuring that only acetylcholine, the endogenous agonist,
      initiates large enough responses to trigger reproduction. 

PMID- 24740857
TI  - Endogenous release of 5-HT modulates the plateau phase of NMDA-induced membrane
      potential oscillations in lamprey spinal neurons.
AB  - The lamprey central nervous system has been used extensively as a model system
      for investigating the networks underlying vertebrate motor behavior. The
      locomotor networks can be activated by application of glutamate agonists, such as
      N-methyl-D-aspartic acid (NMDA), to the isolated spinal cord preparation. Many
      spinal neurons are capable of generating pacemaker-like membrane potential
      oscillations upon activation of NMDA receptors. These oscillations rely on the
      voltage-dependent properties of NMDA receptors in interaction with voltage
      dependent potassium and calcium-dependent potassium (K(Ca)) channels, as well as
      low voltage-activated calcium channels. Upon membrane depolarization, influx of
      calcium will activate K(Ca) channels, which in turn, will contribute to
      repolarization and termination of the depolarized phase. The appearance of the
      NMDA-induced oscillations varies markedly between spinal cord preparations; they
      may either have a pronounced, depolarized plateau phase or be characterized by a
      short-lasting depolarization lasting approximately 200-300 ms without a plateau.
      Both types of oscillations increase in frequency with increased concentrations of
      NMDA. Here, we characterize these two types of membrane potential oscillations
      and show that they depend on the level of endogenous release of 5-HT in the
      spinal cord preparations. In the lamprey, 5-HT acts to block voltage-dependent
      calcium channels and will thereby modulate the activity of K(Ca) channels. When 5
      HT antagonists were administered, the plateau-like oscillations were converted to
      the second type of oscillations lacking a plateau phase. Conversely, plateau-like
      oscillations can be induced or prolonged by 5-HT agonists. These properties are
      most likely of significance for the modulatory action of 5-HT on the spinal
      networks for locomotion.

PMID- 24740856
TI  - Burst firing of neurons in the thalamic reticular nucleus during locomotion.
AB  - This study examined the burst firing of neurons in the motor sector of the
      thalamic reticular nucleus (RE) of the cat. These neurons are inhibitory cells
      that project to the motor thalamus. The firing activity of RE neurons was studied
      during four behaviors: sleep, standing, walking on a flat surface, and accurate
      stepping on crosspieces of a horizontal ladder. Extracellularly recorded firing
      activity was analyzed in 58 neurons that were identified according to their
      receptive fields on the contralateral forelimb. All neurons generated bursts of
      spikes during sleep, half generated bursts of spikes during standing, and one
      third generated bursts of spikes during walking. The majority of bursts were
      sequences of spikes with an exponential buildup of the firing rate followed by
      exponential decay with time constants in the range of 10-30 ms. We termed them
      "full-scale" bursts. All neurons also generated "atypical" bursts, in which the
      buildup of the firing rate deviated from the characteristic order. Burst firing
      was most likely to occur in neurons with receptive fields on the distal forelimb
      and least likely in neurons related to the proximal limb. Full-scale bursts were
      more frequent than atypical bursts during unconstrained walking on the flat
      surface. Bursts of both types occurred with similar probability during accurate
      stepping on the horizontal ladder, a task that requires forebrain control of
      locomotion. We suggest that transformations of the temporal pattern of bursts in
      the inhibitory RE neurons facilitate the tuning of thalamo-cortical signals to
      the complexity of ongoing locomotor tasks. 

PMID- 24740858
TI  - Inhibition of RSK/YB-1 signaling enhances the anti-cancer effect of enzalutamide
      in prostate cancer.
AB  - BACKGROUND: Previously, we have shown that Y-box binding protein-1 (YB-1)
      regulates androgen receptor (AR) expression and contributes to castration
      resistance. However, the mechanism of YB-1 activation remains unknown. In this
      study, we aimed to elucidate the mechanism and role of YB-1 activation in
      relation to castration resistance as well as enzalutamide resistance, with a view
      to developing a novel therapeutic concept for castration-resistant prostate
      cancer (CRPC) treatment. METHODS: The expression and phosphorylation levels of
      ribosomal S6 kinase 1 (RSK1), YB-1 and AR were examined by quantitative PCR and
      Western blotting using prostate cancer cells. In addition, the effects of YB-1
      inhibition using specific siRNA and small molecule inhibitor SL0101 on AR
      expression as well as combination treatment with enzalutamide and SL0101 were
      examined. RESULTS: We found that androgen deprivation, as well as treatment with
      the next-generation anti-androgen enzalutamide, induced RSK1 and YB-1 activation
      followed by AR induction, which could be reversed by YB-1 shutdown and RSK
      inhibitor SL0101. SL0101 and enzalutamide exerted a synergistic tumor-suppressive
      effect on cell proliferation in androgen-dependent prostate cancer LNCaP cells,
      as well as castration-resistant C4-2 cells. Furthermore, the phosphorylation
      levels of RSK1 and YB-1 were elevated in castration- and enzalutamide-resistant
      cells, compared with their parental cells. CONCLUSIONS: Taken together, these
      findings indicate that RSK1/YB-1 signaling contributes to castration as well as
      enzalutamide resistance, and that the therapeutic targeting of RSK1/YB-1
      signaling would be a promising novel therapy against prostate cancer, especially
      CRPC when combined with enzalutamide.

PMID- 24740859
TI  - Spatial distribution, seasonality and trap preference of stable fly, Stomoxys
      calcitrans L. (Diptera: Muscidae), adults on a 12-hectare zoological park.
AB  - Although this study was originally designed to compare the efficacy of two
      different stable fly traps within 10 sites at a 12-ha zoological park, seasonal
      and spatial population distribution data were simultaneously collected. The two
      traps included an Alsynite fiberglass cylindrical trap (AFT) and a blue-black
      cloth target modified into a cylindrical trap (BCT). Both traps were covered with
      sticky sleeves to retain the attracted flies. Paired trap types were placed at
      sites that were 20-100 m apart. Distance between trap pairs within sites ranged
      from 1 to 2 m, and was limited by exhibit design and geography. Both trap types
      reflect/refract ultraviolet (UV) light which attracts adult S. calcitrans. During
      this 15-week study, AFTs captured significantly more stable flies than the BCTs
      at 8 of the 10 sites. Of the 12,557 stable flies found on the traps, 80% and 20%
      were captured by AFTs and BCTs, respectively. The most attractive trap site at
      the zoo was at the goat exhibit where most stable flies were consistently
      captured throughout the study. This exhibit was 100 m from the other exhibits,
      next to a small lake, and adjacent to a field containing pastured exotic
      ungulates, rhea and ostrich. Stable fly populations peaked in early June then
      slowly decreased as the last trapping date approached. We believe this to be the
      first seasonality data collected at a zoological park. Results demonstrate the
      use of urban zoos by stable flies and the need to develop environmentally
      friendly stable fly management systems for zoos.

PMID- 24740860
TI  - Spatio-temporal appearance of alpha-amylase and limit dextrinase in barley
      aleurone layer in response to gibberellic acid, abscisic acid and salicylic acid.
AB  - BACKGROUND: Cereal seed germination involves mobilization of storage reserves in
      the starchy endosperm to support seedling growth. In response to gibberellin
      produced by the embryo the aleurone layer synthesizes hydrolases that are
      secreted to the endosperm for degradation of storage products. In this study
      analysis of intracellular protein accumulation and release from barley aleurone
      layers is presented for the important enzymes in starch degradation: alpha
      amylase and limit dextrinase (LD). RESULTS: Proteins were visualized by
      immunoblotting in aleurone layers and culture supernatants from dissected
      aleurone layers incubated up to 72 h with either gibberellic acid (GA), abscisic
      acid (ABA) or salicylic acid (SA). The results show that alpha-amylase is
      secreted from aleurone layer treated with GA soon after synthesis but the release
      of LD to culture supernatants was significantly delayed and coincided with a
      general loss of proteins from aleurone layers. CONCLUSIONS: Release of LD was
      found to differ from that of amylase and was suggested to depend on programmed
      cell death (PCD). Despite detection of intracellular amylase in untreated
      aleurone layers or aleurone layers treated with ABA or SA, alpha-amylase was not
      released from these samples. Nevertheless, the release of alpha-amylase was
      observed from aleurone layers treated with GA+ABA or GA+SA.

PMID- 24740861
TI  - London GP is cleared of practising female genital mutilation.

PMID- 24740862
TI  - Parental cancer: Health-related quality of life and current psychosocial support
      needs of cancer survivors and their children.
AB  - The presence of cancer and additional parental responsibilities can increase
      strain for individual patients as well as for their children. The construct of
      health-related quality of life (HRQL) is appropriate to measure a combination of
      physical, mental and social consequences as a result of disease. However,
      previous research has merely focused on symptom checklists. This study addresses
      the following questions: (i) does HRQL in children and their parents with cancer
      differ compared to the general population? (ii) Are there any variables that are
      associated with HRQL in children? (iii) What are current psychosocial support
      needs? A population-based survey of 976 survivors (<6 years post diagnosis) with
      minor children between 6 and 18 years (n = 1,449) was conducted with two German
      cancer registries. HRQL was assessed using SF-8 (survivors) and Kidscreen
      (children). The results were compared to normative populations, and predictors
      associated with HRQL in children were evaluated within a multilevel model. We
      found that the HRQL in children was better compared to the norm. Only children
      with support needs had worse HRQL. Older age, having a mother with cancer, having
      a parent not living together with a partner, and worse parental physical and
      mental health influenced HRQL in children. Illness characteristics were
      irrelevant. Even with a mean of 3.5 years after diagnosis, survivors had lower
      physical and mental health compared to the norm. Our findings reinforce the need
      for health professionals to pay attention to younger patients and their children.
      Even years after diagnosis, life might not have returned to normal.

PMID- 24740863
TI  - Family carers of people with cognitive impairment who are admitted to hospital
      experience disruption from their normal routine and use a variety of strategies
      to cope.

PMID- 24740864
TI  - The predictors of successful percutaneous coronary intervention in ostial left
      anterior descending artery chronic total occlusion.
AB  - BACKGROUND: Percutaneous coronary intervention (PCI) to chronic total occlusion
      (CTO) has become one of the treatment strategies in recent era. The ostium of the
      left anterior descending artery (LAD) is one of the most difficult positions for
      CTO revascularization. Until now, limited data has been made available for the
      prediction of successful ostial LAD CTO PCI. OBJECTIVE: The aim of the study was
      to compare the differences between ostial LAD and all other CTOs and to identify
      the predictors of successful ostial LAD CTO PCI. METHODS: This retrospective
      analysis included consecutive patients referred for CTO PCI between January 2001
      and September 2013. Ostial LAD CTO was defined as CTO at the position whose
      distance between lesion and left main bifurcation was less than 1 mm. Baseline
      demographics, lesion characteristics, interventional procedure details, and
      devices were compared between the ostial LAD group and the all other CTOs group.
      The predictors of successful ostial LAD CTO PCI were also evaluated. RESULTS: 621
      patients who underwent CTO PCI were enrolled retrospectively to this study. A
      total of 70 patients of ostial LAD CTO were compared with 551 patients of all
      other CTOs group in this study. Ostial LAD CTO was found to have more bridging
      and better collaterals than all other CTOs. Procedure time, fluoroscopic time,
      contrast volumes, the use of contralateral injection, and the use of the
      retrograde approach were significantly greater in the ostial LAD CTO group. The
      ostial LAD CTO group also had significantly higher J-CTO scores (2.7 +/- 0.8 vs.
      2.2 +/- 1.1, P = 0.011) and higher Syntax Scores (28.3 +/- 6.5 vs. 20.9 +/- 9.7,
      P < 0.001). A slightly lower final success rate, but statistically non
      significant, was observed in the ostial LAD CTO group (80.0% vs. 81.9%, P =
      0.706). Univariate and multivariate logistic regression revealed that without
      antegrade failure and with retrograde success were predictors of the success of
      ostial LAD CTO PCI. Syntax Score was also capable of predicting the ostial LAD
      CTO PCI outcome. J-CTO score was not found to be associated with final success
      for ostial LAD CTO patients. CONCLUSIONS: Ostial LAD CTO resulted in higher
      lesion complexity in J-CTO scores and Syntax Scores. Ostial LAD CTO PCI had a
      slightly lower final success rate than that of all other CTOs PCI with longer
      procedure duration, fluoroscopic time and larger contrast volume. Without
      antegrade failure, with retrograde success, and lower Syntax Score were found to
      predict the success of ostial LAD CTO PCI.

PMID- 24740865
TI  - Blue Button use by patients to access and share health record information using
      the Department of Veterans Affairs' online patient portal.
AB  - OBJECTIVE: The Blue Button feature of online patient portals promotes patient
      engagement by allowing patients to easily download their personal health
      information. This study examines the adoption and use of the Blue Button feature
      in the Department of Veterans Affairs' (VA) personal health record portal, My
      HealtheVet. MATERIALS AND METHODS: An online survey presented to a 4% random
      sample of My HealtheVet users between March and May 2012. Questions were designed
      to determine characteristics associated with Blue Button use, perceived value of
      use, and how Veterans with non-VA providers use the Blue Button to share
      information with their non-VA providers. RESULTS: Of the survey participants
      (N=18 398), 33% were current Blue Button users. The most highly endorsed benefit
      was that it helped patients understand their health history better because all
      the information was in one place (73%). Twenty-one percent of Blue Button users
      with a non-VA provider shared their VA health information, and 87% reported that
      the non-VA provider found the information somewhat or very helpful. Veterans'
      self-rated computer ability was the strongest factor contributing to both Blue
      Button use and to sharing information with non-VA providers. When comparing Blue
      Button users and non-users, barriers to adoption were low awareness of the
      feature and difficulty using the Blue Button. CONCLUSIONS: This study contributes
      to the understanding of early Blue Button adoption and use of this feature for
      patient-initiated sharing of health information. Educational efforts are needed
      to raise awareness of the Blue Button and to address usability issues that hinder
      adoption.

PMID- 24740866
TI  - Single-molecule reconstruction of oligonucleotide secondary structure by atomic
      force microscopy.
AB  - Based on soft-touch atomic force microscopy, a method is described to reconstruct
      the secondary structure of single extended biomolecules, without the need for
      crystallization. The method is tested by accurately reproducing the dimensions of
      the B-DNA crystal structure. Importantly, intramolecular variations in groove
      depth of the DNA double helix are resolved, which would be inaccessible for
      methods that rely on ensemble-averaging. 

PMID- 24740867
TI  - Concise review: the epigenetic contribution to stem cell ageing: can we
      rejuvenate our older cells?
AB  - Although certainly one of the most recognizable characteristics of human biology,
      aging remains one of the least understood. This is largely attributable to the
      fact that aging is both gradual and inherently complex, with almost all aspects
      of physiology and phenotype undergoing steady modification with advancing age.
      The complexity of the aging process does not allow for a single all-encompassing
      definition, yet decades of study using diverse systems, methodologies, and model
      organisms have begun to build a consensus regarding the central physiological
      characteristics of aging. Indeed, such studies have shown that the process of
      aging is invariably accompanied by a diminished capacity to adequately maintain
      tissue homeostasis or to repair tissues after injury. When homeostatic control
      diminishes to the point at which tissue/organ integrity and function are no
      longer sufficiently maintained, physiologic decline ensues, and aging is
      manifested. Inadequate organ homeostasis indicates possible dysfunction of tissue
      specific stem cells. Several mechanisms have been postulated to account for age
      related cellular changes; however, increasing literature evidence suggests that
      age-related changes to the epigenome make a major contribution to the aged
      phenotype. In this review, we discuss the evidence for epigenetic contributions
      to tissue-specific stem cell ageing.

PMID- 24740868
TI  - A randomized comparative effectiveness trial of using cable television to deliver
      diabetes prevention programming.
AB  - OBJECTIVE: To evaluate the use and effectiveness of two "in-home" strategies for
      delivering diabetes prevention programming using cable television. METHODS: An
      individually randomized, two-arm intervention trial including adults with
      diabetes risk factors living in two US cities. Interventions involved a 16
      session lifestyle intervention delivered via "video-on-demand" cable television,
      offered alone versus in combination with web-based lifestyle support tools.
      Repeated measures longitudinal linear regression with imputation of missing
      observations was used to compare changes in body weight. RESULTS: A total of 306
      individuals were randomized and offered the interventions. After 5 months, 265
      (87%) participants viewed at least 1, and 110 (36%) viewed >=9 of the video
      episodes. A total of 262 (86%) participants completed a 5-month weight
      measurement. In intention-to-treat analysis with imputation of missing
      observations, mean weight loss at 5 months for both treatment groups combined was
      3.3% (95% CI 0.7-5.0%), regardless of intervention participation (with no
      differences between randomized groups (P = 0.19)), and was 4.9% (95% CI 2.1-6.5%)
      for participants who viewed >=9 episodes. CONCLUSIONS: In-home delivery of
      evidence-based diabetes prevention programming in a reality television format,
      offered with or without online behavioral support tools, can achieve modest
      weight losses consistent with past implementation studies of face-to-face
      programs using similar content.

PMID- 24740869
TI  - Diagnostic accuracy of the Composite International Diagnostic Interview (CIDI
      3.0) PTSD module among female Vietnam-era veterans.
AB  - The World Health Organization (WHO) Composite International Diagnostic Interview
      (CIDI) posttraumatic stress disorder (PTSD) module is widely used in
      epidemiological studies of PTSD, yet relatively few data attest to the
      instrument's diagnostic utility. The current study evaluated the diagnostic
      utility of the CIDI 3.0 PTSD module with U. S. women Vietnam-era veterans. The
      CIDI and the Clinician-Administered PTSD Scale (CAPS) were independently
      administered to a stratified sample of 160 women, oversampled for current PTSD.
      Both lifetime PTSD and recent (past year) PTSD were assessed within a 3-week
      interval. Forty-five percent of the sample met criteria for a CAPS diagnosis of
      lifetime PTSD, and 21.9% of the sample met criteria for a CAPS diagnosis of past
      year PTSD. Using CAPS as the diagnostic criterion, the CIDI correctly classified
      78.8% of cases for lifetime PTSD (kappa = .56) and 82.0% of past year PTSD cases
      (kappa = .51). Estimates of diagnostic performance for the CIDI were sensitivity
      of .61 and specificity of .91 for lifetime PTSD and sensitivity of .71 and
      specificity of .85 for past-year PTSD. Results suggest that the CIDI has good
      utility for identifying PTSD, though it is a somewhat conservative indicator of
      lifetime PTSD as compared to the CAPS. 

PMID- 24740870
TI  - Outcome of depression and anxiety after war: a prospective epidemiologic study of
      children and adolescents.
AB  - Prospective studies of children exposed to war have not investigated disorders
      other than posttraumatic stress disorder (PTSD) and have methodological
      limitations. From a stratified random sample of 386 children and adolescents who
      had been interviewed 3 weeks after war exposure (Phase 1) a random subsample (N =
      143) was interviewed a year later (Phase 2). PTSD, major depressive disorder
      (MDD), separation anxiety disorder (SAD), overanxious disorder (OAD), and
      psychosocial stressors were assessed using structured interviews administered to
      both children and adolescents and their parents. The prevalence of disorders
      among the 143 at Phase 1 was MDD 25.9%, SAD 16.1%, OAD 28.0%, and PTSD 26.0%,
      with 44.1% having any disorder. At Phase 2 the prevalence was MDD, 5.6%; SAD,
      4.2%; OAD, 0%; and PTSD, 1.4%, with 9.2% having any disorder. Occurrence of
      disorders at Phase 1 was associated with older age, prewar disorders, financial
      problems, fear of being beaten, and witnessing any war event (ORs ranged from 2.5
      to 28.6). Persistence of disorders to Phase 2 was associated with prewar
      disorders (OR = 6.0) and witnessing any war event (OR = 14.3). There are
      implications for detection of at-risk cases following wars by screening for
      adolescents exposed to family violence, those with prewar disorders, and those
      who directly witnessed war events to target them for specific interventions. 

PMID- 24740871
TI  - Relationships of posttraumatic stress symptoms and sleep measures to cognitive
      performance in young-adult African Americans.
AB  - Disturbed sleep is a prominent feature of posttraumatic stress disorder (PTSD).
      PTSD and disrupted sleep have been independently linked to cognitive deficits;
      however, synergistic effects of PTSD and poor sleep on cognition have not been
      investigated. The purpose of this study was to examine the effects of PTSD
      symptoms and objectively measured disruptions to sleep on cognitive function.
      Forty-four young-adult African American urban residents comprised the study
      sample. The Clinician-Administered PTSD Scale (CAPS; Blake et al., 1995) was
      utilized to determine the severity of PTSD symptoms. Participants underwent 2
      consecutive nights of polysomnography. The Automated Neuropsychological
      Assessment Metrics (Reeves, Winter, Bleiberg, & Kang, ) was utilized to assess
      sustained attention and the Rey Auditory Verbal Learning Test (Schmidt, ) was
      used to evaluate verbal memory. PTSD symptom severity, r(42) = .40, p = .007, was
      significantly associated with omission errors on the sustained attention task,
      and sleep duration, r(42) = .41, p = .006, and rapid eye movement sleep, r(42) =
      .43, p = .003, were positively correlated with verbal memory. There was an
      interaction of PTSD symptom severity and sleep duration on omission errors such
      that more than 7 hours 12 minutes of sleep mitigated attentional lapses that were
      associated with PTSD.

PMID- 24740873
TI  - Emodin attenuates systemic and liver inflammation in hyperlipidemic mice
      administrated with lipopolysaccharides.
AB  - Non-alcoholic fatty liver disease (NAFLD) is a major epidemics of the modern
      societies and has an inflammatory component in the pathogenesis. However,
      approved anti-inflammatory therapies are not currently available for the
      prevention of the transition from simple steatosis to non-alcoholic
      steatohepatitis (NASH). We aimed to test if a Chinese herb-derived compound,
      emodin could halt the simple steatosis to NASH transition. LDLR-/- mice were fed
      a western-type diet for 10 weeks; and during the last four weeks, the mice were
      intra-peritoneally injected daily with LPS with or without emodin. Systemic
      inflammation was evaluated by measurement of serum levels of cytokines and
      chemokines and flow cytometric analysis of spleen leukocytes. Liver inflammation
      was determined by histology, immunocytochemistry and flow cytometry. Quantitative
      real-time PCR and Western blot were performed to examine the effects of emodin on
      LPS-induced inflammatory responses in macrophages. Our data showed that emodin
      ameliorated systemic inflammation, reduced inflammatory cell infiltration in the
      liver, and attenuated liver function impairment. In vitro experiments showed
      emodin inhibited LPS-induced expression of proinflammatory cytokines in
      macrophages through suppressing Erk1/2 and p38 signaling. In conclusion, emodin
      inhibited the transition from simple steatosis to NASH in hyperlipidemic mice
      challenged with LPS through suppressing systemic and macrophage inflammation.
      Emodin may be developed as a therapy for NAFLD by the virtue of its anti
      inflammatory effects.

PMID- 24740874
TI  - Potentiation of cisplatin-induced nephrotoxicity by repeated exposure to diesel
      exhaust particles: An experimental study in rats.
AB  - Several epidemiological and clinical studies have shown that exposure to
      particulate air pollution is associated with increases in morbidity and
      mortality, and this is more evident in patients with renal diseases. However, the
      basis of the possible exacerbating effect of particulate air pollution on animal
      model of renal injury has received scant attention. Here, we assessed the effect
      of repeated exposure to diesel exhaust particles (DEP) on cisplatin (CP)-induced
      nephrotoxicity in rats. DEP (0.5 m/kg) was intratracheally (i.t.) instilled every
      second day for eight days (a total of five exposures). CP, 6 mg/kg was given 1 h
      before the third exposure to DEP. Two days following the last exposure to either
      DEP or saline (control), various renal endpoints were measured. Water intake,
      urine volume, and relative kidney weight were significantly increased in CP + DEP
      versus DEP and CP + saline versus saline. Plasma creatinine increased and
      creatinine clearance decreased in CP + DEP versus DEP and CP + saline versus
      saline. Interestingly, blood urea nitrogen, albumin concentrations, and gamma
      glutamyl transpeptidase (GGT) activity in urine were significantly increased in
      DEP + CP compared with either DEP or saline + CP. The combination of DEP and CP
      enhanced kidney injury molecule-1, neutrophil gelatinase-associated lipocalin, 8
      isoprostane and total nitric oxide in the kidney compared with either saline + CP
      or DEP. Similarly, systolic blood pressure was increased in CP + DEP versus CP +
      saline or DEP. The renal tubular necrosis observed in kidneys of CP-treated rats
      was aggravated by the combination of CP + DEP. We conclude that repeated exposure
      to DEP potentiated CP-induced nephrotoxicity. Our data provide experimental
      evidence that patients with kidney injury could be at higher risk than the
      general population.

PMID- 24740872
TI  - A strategy for integrating essential three-dimensional microphysiological systems
      of human organs for realistic anticancer drug screening.
AB  - Cancer is one of the leading causes of morbidity and mortality around the world.
      Despite some success, traditional anticancer drugs developed to reduce tumor
      growth face important limitations primarily due to undesirable bone marrow and
      cardiovascular toxicity. Many drugs fail in clinical development after showing
      promise in preclinical trials, suggesting that the available in vitro and animal
      models are poor predictors of drug efficacy and toxicity in humans. Thus, novel
      models that more accurately mimic the biology of human organs are necessary for
      high-throughput drug screening. Three-dimensional (3D) microphysiological systems
      can utilize induced pluripotent stem cell technology, tissue engineering, and
      microfabrication techniques to develop tissue models of human tumors, cardiac
      muscle, and bone marrow on the order of 1 mm(3) in size. A functional network of
      human capillaries and microvessels to overcome diffusion limitations in nutrient
      delivery and waste removal can also nourish the 3D microphysiological tissues.
      Importantly, the 3D microphysiological tissues are grown on optically clear
      platforms that offer non-invasive and non-destructive image acquisition with
      subcellular resolution in real time. Such systems offer a new paradigm for high
      throughput drug screening and will significantly improve the efficiency of
      identifying new drugs for cancer treatment that minimize cardiac and bone marrow
      toxicity.

PMID- 24740875
TI  - Suppressive effects of irisflorentin on LPS-induced inflammatory responses in RAW
      264.7 macrophages.
AB  - Irisflorentin, a naturally occurring isoflavone, is an abundant active
      constituent in Rhizoma Belamcandae. Although some chemical studies have been
      reported, pharmacological actions of irisflorentin are not well studied. In this
      study, we demonstrate the anti-inflammatory activity of irisflorentin in
      lipopolysaccharides (LPS)-stimulated RAW 264.7 macrophages. Irisflorentin
      markedly reduces the transcriptional and translational levels of inducible nitric
      oxide synthase (iNOS) as well as the production of NO. Furthermore, it also
      significantly inhibits TNF-alpha, IL-1beta and IL-6 at both the transcriptional
      and translational levels. These effects mainly act via ERK1/2 - and p38-mediated
      the activator protein-1 (AP-1) rather than the nuclear factor-kappaB (NF-kappaB)
      pathway. Thus, our study elucidates the anti-inflammatory mechanism of
      irisflorentin in LPS-activated RAW 264.7 macrophages.

PMID- 24740876
TI  - Ossification defects detected in CT scans represent early osteochondrosis in the
      distal femur of piglets.
AB  - The purpose of the current study was to validate the use of CT for selection
      against osteochondrosis in pigs by calculating positive predictive value and
      comparing it to the positive predictive value of macroscopic evaluation, using
      histological examination as the reference standard. Eighteen male, hereditarily
      osteochondrosis-predisposed piglets underwent terminal examination at biweekly
      intervals from the ages of 82-180 days old, including CT scanning, macroscopic,
      and histological evaluation of the left distal femur. Areas of ischemic
      chondronecrosis (osteochondrosis) were confirmed in histological sections from
      44/56 macroscopically suspected lesions, resulting in a positive predictive value
      of 79% (95% CI: 67-84%). Suspected lesions, that is; focal, radiolucent defects
      in the ossification front in CT scans corresponded to areas of ischemic
      chondronecrosis in 36/36 histologically examined lesions, resulting in a positive
      predictive value of 100% (95% CI: 90-100%). CT was superior to macroscopic
      evaluation for diagnosis of early stages of osteochondrosis in the distal femur
      of piglets. The current histologically validated observations can potentially be
      extrapolated to diagnostic monitoring of juvenile osteochondritis dissecans in
      children, or to animal models of human juvenile articular cartilage injury and
      repair.

PMID- 24740877
TI  - A twisted wire-shaped dual-function energy device for photoelectric conversion
      and electrochemical storage.
AB  - A wire-shaped energy device that can perform photoelectric conversion and
      electrochemical storage was developed through a simple but effective twisting
      process. The energy wire exhibited a high energy conversion efficiency of 6.58 %
      and specific capacitance of 85.03 MUF cm(-1) or 2.13 mF cm(-2), and the two
      functions were alternately realized without sacrificing either performance.

PMID- 24740878
TI  - Parkinson's disease-linked mutations in VPS35 induce dopaminergic
      neurodegeneration.
AB  - Mutations in the vacuolar protein sorting 35 homolog (VPS35) gene at the PARK17
      locus, encoding a key component of the retromer complex, were recently identified
      as a new cause of late-onset, autosomal dominant Parkinson's disease (PD). Here
      we explore the pathogenic consequences of PD-associated mutations in VPS35 using
      a number of model systems. VPS35 exhibits a broad neuronal distribution
      throughout the rodent brain, including within the nigrostriatal dopaminergic
      pathway. In the human brain, VPS35 protein levels and distribution are similar in
      tissues from control and PD subjects, and VPS35 is not associated with Lewy body
      pathology. The common D620N missense mutation in VPS35 does not compromise its
      protein stability or localization to endosomal and lysosomal vesicles, or the
      vesicular sorting of the retromer cargo, sortilin, SorLA and cation-independent
      mannose 6-phosphate receptor, in rodent primary neurons or patient-derived human
      fibroblasts. In yeast we show that PD-linked VPS35 mutations are functional and
      can normally complement VPS35 null phenotypes suggesting that they do not result
      in a loss-of-function. In rat primary cortical cultures the overexpression of
      human VPS35 induces neuronal cell death and increases neuronal vulnerability to
      PD-relevant cellular stress. In a novel viral-mediated gene transfer rat model,
      the expression of D620N VPS35 induces the marked degeneration of substantia nigra
      dopaminergic neurons and axonal pathology, a cardinal pathological hallmark of
      PD. Collectively, these studies establish that dominant VPS35 mutations lead to
      neurodegeneration in PD consistent with a gain-of-function mechanism, and support
      a key role for VPS35 in the development of PD. 

PMID- 24740879
TI  - Dissecting the mechanisms underlying the accumulation of mitochondrial DNA
      deletions in human skeletal muscle.
AB  - Large-scale mitochondrial DNA (mtDNA) deletions are an important cause of
      mitochondrial disease, while somatic mtDNA deletions cause focal respiratory
      chain deficiency associated with ageing and neurodegenerative disorders. As mtDNA
      deletions only cause cellular pathology at high levels of mtDNA heteroplasmy, an
      mtDNA deletion must accumulate to levels which can result in biochemical
      dysfunction-a process known as clonal expansion. A number of hypotheses have been
      proposed for clonal expansion of mtDNA deletions, including a replicative
      advantage for deleted mitochondrial genomes inferred by their smaller size-
      implying that the largest mtDNA deletions would also display a replicative
      advantage over smaller mtDNA deletions. We proposed that in muscle fibres from
      patients with mtDNA maintenance disorders, which lead to the accumulation of
      multiple mtDNA deletions, we would observe the largest mtDNA deletions spreading
      the furthest longitudinally through individual muscle fibres by means of a
      greater rate of clonal expansion. We characterized mtDNA deletions in patients
      with mtDNA maintenance disorders from a range of 'large' and 'small' cytochrome c
      oxidase (COX)-deficient regions in skeletal muscle fibres. We measured the size
      of clonally expanded deletions in 62 small and 60 large individual COX-deficient
      f regions. No significant difference was observed in individual patients or in
      the total dataset (small fibre regions mean 6.59 kb--large fibre regions mean
      6.51 kb). Thus no difference existed in the rate of clonal expansion throughout
      muscle fibres between mtDNA deletions of different sizes; smaller mitochondrial
      genomes therefore do not appear to have an inherent replicative advantage in
      human muscle.

PMID- 24740880
TI  - The role of IL-6 572 C/G, 190 C/T, and 174 G/C gene polymorphisms in children's
      obesity.
AB  - The aim of this study was to establish the correlations between the polymorphisms
      of the genes interleukin (IL)-6 572, 190, and 174 in obese children. We assessed
      222 hospitalized children divided into two groups: group I (control) included 110
      patients with normal nutritional status, and group II consisted of 102 obesity
      patients. The two groups underwent IL-6 572 C/G, 190 C/T, and 174 G/C
      polymorphism testing, measurement of anthropometric parameters (mid-upper arm
      circumference and tricipital skinfold thickness), and paraclinical evaluation
      (protein, albumin, leptin, adiponectin, and vascular endothelial growth factor
      (VEGF)). We observed that phenotype CC was more frequent in obese children for IL
      6 572 (p = 0.0001), whereas CG heterozygotes were more frequent in the obese
      group for the IL-6 190 gene (62.7 %; p = 0.0001). Leptin was dependent on IL-6
      572 and IL-6 174 gene polymorphisms and albumin, whereas adiponectin was
      dependent on the IL-6 174 gene polymorphism. Body mass index (BMI), mid-upper arm
      circumference (MUAC), and tricipital skinfold thickness (TST) serum albumin
      levels correlated with C allele carriers of the IL-6 572 and IL-6 190 genes in
      children with obesity, whereas the CC genotype of IL-6 174 was a protective
      factor for obesity. CONCLUSION: Obesity is most frequently associated in children
      with IL-6 174 C allele carriers and with IL-6 190 C allele carriers.

PMID- 24740882
TI  - Severe catheter kinking and entrapment during transradial coronary angiography:
      percutaneous retrieval using a sheathless guide catheter.
AB  - The transradial (TR) approach for coronary angiography and intervention is
      increasingly used worldwide because of several advantages such as reduced
      bleeding and vascular complications. During TR procedures, aggressive catheter
      manipulation in the setting of complex and tortuous arterial anatomy can lead to
      catheter kinking and entrapment. Several percutaneous retrieval techniques using
      either homolateral radial access or femoral access have been described
      previously. We demonstrate, for the first time, the use of a sheathless guide
      catheter as a rescue technique to successfully retrieve a severely kinked and
      entrapped diagnostic catheter during TR access. (c) 2014 Wiley Periodicals, Inc. 

PMID- 24740881
TI  - Perinatal arrhythmias.
AB  - Cardiac arrhythmias are very frequent in fetuses and newborns. The prognosis
      depends on the nature of the arrhythmias but is most often either spontaneously
      benign or following short-term medication administration. A correct diagnosis is
      essential for both management and prognosis. It is based on echocardiography
      during the fetal period and mainly on history, physical exam, and
      electrocardiogram after birth, but other modalities are available to record
      transient arrhythmic events. Irregular rhythms are mostly benign and rarely
      require therapy. In most fetuses and infants, tachyarrhythmias resolve
      spontaneously or require short-term administration of antiarrhythmics.
      Approximately one third of these may recur later on, especially during
      adolescence. Persistent bradyarrhythmias might require pacemaker implantation
      when associated with failure to thrive or with risk of sudden death. CONCLUSION:
      Arrhythmias in fetuses and infants are very common and mostly benign. History,
      physical exam, and recording of the arrhythmia are essential to make a correct
      diagnosis and establish an appropriate management for the rare potentially
      harmful arrhythmias.

PMID- 24740883
TI  - Monoclinic porous BiVO4 networks decorated by discrete g-C3N4 nano-islands with
      tunable coverage for highly efficient photocatalysis.
AB  - An efficient g-C3N4/BiVO4 heterojunction photocatalyst is constructed with BiVO4
      networks decorated by discrete g-C3N4 nano-islands with controllable coverage.
      The as-synthesized g-C3N4/BiVO4 photo-catalyst shows superior visible light
      photocatalytic activity. The enhanced photocatalytic activity can be ascribed to
      increased charge separation efficiency, separated redox reaction sites, fully
      exposed reactive interfaces, and excellent visible light response of g-C3N4/BiVO4
      composite.

PMID- 24740884
TI  - Molecular evidence for OCT4-induced plasticity in adult human fibroblasts
      required for direct cell fate conversion to lineage specific progenitors.
AB  - Here we characterize the molecular and biological requirements for OCT4
      plasticity induction in human skin derived fibroblasts (hFibs) that allows direct
      conversion of cell fate without iPSC formation. Our results indicate that adult
      hFibs not only require OCT4 but also short-term exposure to reprogramming media
      (RM) to successfully undergo direct conversion to early hematopoietic and neural
      progenitor fates. RM was found to be essential in this process and allowed for
      unique changes in global gene expression specific to the combined effects of OCT4
      and treatment with reprogramming media to establish a plastic state. This
      molecular state of hFib plasticity was distinct from transient expression of a
      full complement of iPSC reprogramming factors consistent with a lack in molecular
      hallmarks of iPSC formation. Human Fib-derived OCT4 plastic cells display
      elevated levels of developmentally related genes associated with multiple
      lineages, but not those associated with pluripotency. In response to changes in
      the extracellular environment, plastic OCT4-expressing hFibs further activate
      genes involved in hematopoietic as well as tripotent neural progenitor biology
      that allow cell fate conversion. Our study provides a working definition of hFib
      induced plasticity using OCT4 and a deconvoluted system to elucidate the process
      of direct cell fate reprogramming.

PMID- 24740886
TI  - Male gonadal differentiation and the paedomorphic evolution of the testis in
      Teleostei.
AB  - Testis differentiation from representatives of the Otophysi (Cyprinus carpio),
      Percomorpha (Amatitlania nigrofasciata), and Atherinomorpha (Poecilia reticulata)
      was comparatively described. In the undifferentiated gonad of C. carpio, the
      primordial germ cells (PGCs) are scattered throughout the gonads while in A.
      nigrofasciata and P. reticulata the PGCs are restricted to the ventral periphery.
      In the dorsal region of the developing gonads, with the exception of C. carpio,
      somatic cell rearrangements result in the differentiation of the sperm duct. Pre
      Sertoli cells wrap around single spermatogonia forming cysts that proliferate
      forming acinar-clusters. In C. carpio and A. nigrofasciata, the cysts in each
      acinar-cluster move away from each other, creating a central lumen. In C. carpio,
      the acinar-clusters then fuse to each other forming tubules that become lined by
      the germinal epithelium. Subsequently, the tubules anastomose dorsally and create
      the sperm duct. In A. nigrofasciata, the acinar-clusters elongate, forming
      lobules that individually connect to the sperm duct. These are lined by the
      germinal epithelium. In P. reticulata, the spermatogonial cysts remain in the
      acinar-cluster organization. Subsequently, developing ducts connect each cluster
      to the sperm duct and lobules subsequently develop. In the differentiated testis
      of C. carpio and A. nigrofasciata, spermatogonia are distributed along the
      lengths of the anastomosing tubules or lobules, respectively. However, in P.
      reticulata, the spermatogonia remain restricted to the terminal end of the
      lobules. Considering testis ontogeny, the spermatogonial acinar-cluster is the
      adult characteristic of more derived taxa that approximate the early gonad
      developmental stages of the basal taxa.

PMID- 24740887
TI  - Anxiety in first year medical students taking gross anatomy.
AB  - To study anxiety levels in first-year medical students taking gross anatomy.
      Thirty medical students per year, for 2 years, completed the Beck Anxiety
      Inventory (BAI) 10 times during a 13-week gross anatomy course. In addition,
      behavioral observations were made by a psychiatrist during gross anatomy for
      demonstrations of assertive, destructive, neutral, or passive behavior.
      Additional qualitative outcome measures were group exit interviews with the
      faculty and students. The mean BAI for all 60 students per year, for 2 years, was
      2.19 +/- 3.76, 93% of the scores indicated minimal anxiety, and 89% of BAI values
      were less than five which confirmed a minimal level of anxiety. The low level of
      reported BAI contrasted sharply with verbal reports by the same students and face
      to-face exit interviews with the psychiatrist. Symptoms of stress and anxiety
      emerged as a result of these conversations. The high levels of subjective stress
      and anxiety revealed by the interviews were unknown to the gross anatomy faculty.
      The low scores of students on the BAI's stand in sharp contrast to the BAI's
      reported for medical students in other published reports. Although it is possible
      that our students were truthfully devoid of anxiety, it is more likely that our
      students were denying even minimal anxiety levels. There have been reports that
      medical students feel that admitting stress, depression, or anxiety put their
      competitiveness for a residency at risk. We conclude that students may be in
      frank denial of experiencing anxiety and, if so, this behavior is not conducive
      to good mental health.

PMID- 24740888
TI  - Spatial control over brush growth through sunlight-induced atom transfer radical
      polymerization using dye-sensitized TiO2 as a photocatalyst.
AB  - Simulated-sunlight induced atom transfer radical polymerization is used for
      spatial control over polymer brush growth by in situ photo-generation of the
      Cu(I) /L activator complex from its higher oxidation state Cu(II) /L deactivator
      complex using dye sensitized titanium dioxide nano-particles. The polymerization
      is well controlled under sunlight irradiation. Another attractive feature of this
      method is the possibility of creating various patterned surfaces of brushes using
      photomasks. When a nanoporous alumina oxide membrane is used as the template for
      confinement diffusion of photogenerated Cu(I) /L catalyst, patterns with sub-50
      nm resolution are obtained. 

PMID- 24740889
TI  - Ask when--not just whether--it's a risk: How regional context influences local
      causes of diarrheal disease.
AB  - Contemporary epidemiology is enriched when it incorporates ecological concepts
      about systems and dependencies. With regard to diarrheal disease, the causes of
      which are many and interacting, the dynamics of within- and between-community
      disease transmission have distinct components but are also linked in important
      ways. However, few investigators have studied how regional-scale disease dynamics
      affect local patterns of diarrheal disease transmission. Characterizing this
      dependence is important for identifying local- and regional-level transmission
      pathways. We used data from active surveillance of diarrheal disease prevalence
      gathered from February 2004 through July 2007 in 21 neighboring Ecuadorian
      villages to estimate how disease prevalence in spatially and temporally proximate
      villages modulates the influences of village-level risk and protective factors.
      We found that the impact of local, village-level interventions such as improved
      latrines and water treatment can be quite different under conditions of high and
      low regional disease prevalence. In particular, water treatment was effective
      only when regional disease prevalence was low, suggesting that person-to-person
      spread, not waterborne spread, is probably responsible for most between-village
      transmission in this region. Additional regional-scale data could enhance our
      understanding of how regional-scale transmission affects local-scale dynamics.

PMID- 24740885
TI  - Medial vascular calcification revisited: review and perspectives.
AB  - Vascular calcifications (VCs) are actively regulated biological processes
      associated with crystallization of hydroxyapatite in the extracellular matrix and
      in cells of the media (VCm) or intima (VCi) of the arterial wall. Both patterns
      of VC often coincide and occur in patients with type II diabetes, chronic kidney
      disease, and other less frequent disorders; VCs are also typical in senile
      degeneration. In this article, we review the current state of knowledge about the
      pathology, molecular biology, and nosology of VCm, expand on potential mechanisms
      responsible for poor prognosis, and expose some of the directions for future
      research in this area. 

PMID- 24740890
TI  - Testing the measurement invariance of the Eating Disorder Inventory in
      nonclinical samples of Hispanic and Caucasian women.
AB  - OBJECTIVE: The factor structure of the Eating Disorder Inventory (EDI) has not
      been thoroughly tested in Hispanic populations, yet researchers commonly use this
      instrument in Hispanic samples. Thus, it is important to establish the validity
      of the EDI in Hispanic populations. This article investigated measurement
      invariance of the EDI's three eating- and weight-related (eat/wt) scales because
      they are the most frequently used and are often used in isolation. These scales
      include Drive for Thinness, Bulimia, and Body Dissatisfaction. METHOD: Female
      undergraduates were recruited for a study on body image. The final sample (N =
      688) included participants categorized as Hispanic (N = 385) or Caucasian (N =
      303). They completed the EDI-3 and a measure of acculturation. RESULTS:
      Measurement invariance analyses of the EDI-3 in Caucasian and Hispanic samples
      were conducted. The configural model provided an acceptable fit, providing
      support for the three-factor structure of the eat/wt scales in both the Caucasian
      and the Hispanic sample. However, weak invariance of the three-factor structure
      was not supported. When measurement invariance analyses were conducted on the
      three eat/wt scales separately, Drive for Thinness was the only scale to
      demonstrate measurement invariance. DISCUSSION: The theoretical three-factor
      structure of the EDI eat/wt scales was supported in both ethnic groups.
      Furthermore, the Drive for Thinness scale can readily be used to make group
      comparisons across nonclinical samples of Caucasian and Hispanic women, but
      researchers should be cautious when using the other two eat/wt scales to make
      comparisons across these two groups.

PMID- 24740891
TI  - Propeller flap reconstruction of abdominal defects: review of the literature and
      case report.
AB  - The abdominal wall is perfused anteriorly by the superior and deep epigastric
      vessels with a smaller contribution from the superficial system. The lateral
      abdominal wall is perfused predominantly from perforators arising from the
      intercostal vessels. Reconstruction of soft tissue defects involving the abdomen
      presents a difficult challenge for reconstructive surgeons. Pedicle perforator
      propeller flaps can be used to reconstruct defects of the abdomen, and here we
      present a thorough review of the literature as well as a case illustrating the
      perforasome propeller flap concept. A patient underwent resection for
      dermatofibrosarcoma protuberans resulting in a large defect of the epigastric
      soft tissue. A propeller flap was designed based on a perforator arising from the
      superior deep epigastric vessels and was rotated 90 degrees  into the defect
      allowing primary closure of the donor site. The patient healed uneventfully and
      was without recurrent disease 37 months following reconstruction. Perforator
      propeller flaps can be used successfully in reconstruction of abdominal defects
      and should be incorporated into the armamentarium of reconstructive microsurgeons
      already facile with perforator dissections.

PMID- 24740892
TI  - Visible-light-induced photoredox catalysis with a tetracerium-containing
      silicotungstate.
AB  - The development of visible-light-induced photocatalysts for chemoselective
      functional group transformations has received considerable attention.
      Polyoxometalates (POMs) are potential materials for efficient photocatalysts
      because their properties can be precisely tuned by changing their constituent
      elements and structures and by the introduction of additional metal cations.
      Furthermore, they are thermally and oxidatively more stable than the frequently
      utilized organometallic complexes. The visible-light-responsive tetranuclear
      cerium(III)-containing silicotungstate TBA6[{Ce(H2O)}2{Ce(CH3CN)}2(MU4-O)(gamma
      SiW10O36)2] (CePOM; TBA=tetra-n-butylammonium) has now been synthesized; when
      CePOM was irradiated with visible light (lambda>400 nm), a unique intramolecular
      Ce(III)-to-POM(W(VI)) charge transfer was observed. With CePOM, the
      photocatalytic oxidative dehydrogenation of primary and secondary amines as well
      as the alpha-cyanation of tertiary amines smoothly proceeded in the presence of
      O2 (1 atm) as the sole oxidant.

PMID- 24740893
TI  - Constancy in an inconstant world: moving beyond constant temperatures in the
      study of reptilian incubation.
AB  - Variable environmental conditions can alter the phenotype of offspring,
      particularly in ectothermic species such as reptiles. Despite this, the majority
      of studies on development in reptiles have been carried out under constant
      conditions in the laboratory, raising the question of just how applicable those
      investigations are to natural conditions? Here, we first review what we have
      learned from these constant-temperature studies. Second, we examine the
      importance of temperature fluctuations for development in reptiles and highlight
      the outcomes of studies conducted under fluctuating conditions. Next, we report
      our findings from a new study that examines how the frequency of fluctuations in
      temperature experienced during development affects phenotype. Finally, we suggest
      some areas in need of additional research so that we can better understand the
      complex interactions of temperature and physiology, particularly in species with
      temperature-dependent sex determination. For questions aimed at understanding the
      complex effects of the environment on phenotype, we must move toward studies that
      better capture environmental variation. By taking such an approach, it may be
      possible to predict more accurately how these thermally sensitive organisms will
      respond to environmental perturbations, including climatic change. 

PMID- 24740894
TI  - Dual-Source Computed Tomography for Chronic Total Occlusion of Coronary Arteries.
AB  - OBJECTIVES: We compared dual-source CT (DSCT) and conventional angiography (CA)
      in evaluation of chronic total occlusion (CTO) of coronary arteries. BACKGROUND:
      Percutaneous coronary intervention (PCI) in CTO is technically difficult and has
      comparatively lower success rate than intervention in non-occluded artery.
      Accurate assessment of lesion morphology is an important determinant of PCI
      success in CTO. METHODS: Nineteen symptomatic patients (18 men, age: 58.6 +/-
      10.6 years) with a CTO on CA were subjected to a DSCT (Definition, Siemens,
      Germany). Heart rate (HR) control was not performed. Dedicated post-processing
      software was used for lesion analysis on both modalities. Presence of bridging
      collaterals, stump morphology, calcification, side branch, proximal tortuosity,
      occlusion length, distal vessel interpretability, and distal lesions were
      statistically compared. RESULTS: There were 20 CTOs. HR during DSCT ranged from
      53 to 131 bpm. Bridging collaterals were seen in 3/20 (15%) lesions on CA and in
      none on DSCT. Stump anatomy and side branch were identified equally well. Plaque
      calcification was identified in 5/20 (25%) lesions on CA and in 12/20 (60%)
      lesions on DSCT (P = 0.025). Nature and extent of calcification were better
      visualized on DSCT. No proximal tortuosity was noted. Distal vessel was better
      interpretable on DSCT (15/20; 75%) compared to CA (9/20; 45%) (P = 0.05). No
      significant difference in lesion length was noted. CONCLUSION: DSCT performs as
      well as CA for most features of CTO. Avoidance of need to control HR, ability to
      better detect and characterize calcium and to interpret distal vessels make it a
      useful pre-intervention investigation. (c) 2014 Wiley Periodicals, Inc.

PMID- 24740895
TI  - Screening epidermal growth factor receptor antagonists from Radix et Rhizoma
      Asari by two-dimensional liquid chromatography.
AB  - Radix et Rhizoma Asari is a traditional Chinese medicine, and has many
      pharmacological effects, such as calming, analgesia, anti-inflammation,
      antiarrhythmic, antihypertensive, antivirus, etc. But few studies have screened
      the active compounds from extracts of Radix et Rhizoma Asari for tumor therapy.
      In this study, a two-dimensional liquid chromatography system was built to screen
      active compounds acting on epidermal growth factor receptor (EGFR) from Radix et
      Rhizoma Asari. The screening result showed that asarinin from Radix et Rhizoma
      Asari was the targeted component that could act on EGFR specificity. The
      competitive binding assay and molecular docking assay results showed asarinin
      binding with EGFR in similar manner as with gefitinib, which was used as a
      positive control drug. Then the antitumor effect of asarinin was studied through
      cell growth assay in vitro. The results showed that gefitinib and asarinin could
      inhibit highly expressed EGFR cell growth in a dose-dependent manner in the range
      of dose from 0.10 to 102.4 MUM. This two-dimensional liquid chromatography system
      will be a useful method in drug discovery from natural medicinal herbs for
      searching potential antitumor candidates. 

PMID- 24740896
TI  - An approach toward the development of core syllabuses for the anatomical
      sciences.
AB  - There is increasingly a call for clinical relevance in the teaching of the
      biomedical sciences within all health care programs. This presupposes that there
      is an understanding of what is "core" material within the curriculum. To date,
      the anatomical sciences have been poorly served by the development of core
      syllabuses, although there have been commendable attempts to define a core
      syllabus for gross anatomy in medicine and for some medical specialties. The
      International Federation of Associations of Anatomists and the European
      Federation for Experimental Morphology aim to formulate, on an international
      basis, core syllabuses for all branches of the anatomical sciences. This is being
      undertaken at the initial stage using Delphi Panels consisting of a team of
      anatomists, scientists, and clinicians who evaluate syllabus content and accord
      each element/topic "essential," "important," "acceptable," or "not required"
      status. Their initial conjectures, published on the International Federation of
      Associations of Anatomists' website, provide merely a framework to enable
      anatomical (and other cognate learned) societies and individual anatomists,
      clinicians, and students to comment upon the syllabuses. This article presents
      the concepts and methodological approaches underlying the hybrid Delphi process
      employed. Preliminary findings relating to the development of a neuroanatomy core
      syllabus are provided to illustrate the methods initially employed by a Delphi
      Panel. The approach is novel in that it is international in scope, is
      conceptually democratic, and is developmentally fluid in terms of availability
      for amendment. The aim is to set internationally recognized standards and thus to
      provide guidelines concerning anatomical knowledge when engaged in course
      development.

PMID- 24740897
TI  - OODA of graph and tree-structured data.
AB  - This is a discussion of the paper: "Overview of object oriented data analysis" by
      J. Steve Marron and Andres M. Alonso. 

PMID- 24740898
TI  - Concise review: androgen receptor differential roles in stem/progenitor cells
      including prostate, embryonic, stromal, and hematopoietic lineages.
AB  - Stem/progenitor (S/P) cells are special types of cells that have the ability to
      generate tissues throughout their entire lifetime and play key roles in the
      developmental process. Androgen and the androgen receptor (AR) signals are the
      critical determinants in male gender development, suggesting that androgen and AR
      signals might modulate the behavior of S/P cells. In this review, we summarize
      the AR effects on the behavior of S/P cells, including self-renewal,
      proliferation, apoptosis, and differentiation in normal S/P cells, as well as
      proliferation, invasion, and self-renewal in prostate cancer S/P cells. AR plays
      a protective role in the oxidative stress-induced apoptosis in embryonic stem
      cells. AR inhibits the self-renewal of embryonic stem cells, bone marrow stromal
      cells, and prostate S/P cells, but promotes their differentiation except for
      adipogenesis. However, AR promotes the proliferation of hematopoietic S/P cells
      and stimulates hematopoietic lineage differentiation. In prostate cancer S/P
      cells, AR suppresses their self-renewal, metastasis, and invasion. Together, AR
      differentially influences the characteristics of normal S/P cells and prostate
      cancer S/P cells, and targeting AR might improve S/P cell transplantation
      therapy, especially in embryonic stem cells and bone marrow stromal cells.

PMID- 24740899
TI  - Conjugated polymer patterning through photooxidative backbone cleavage.
AB  - Photolithographic patterning of a xanthate precursor to poly(3,4-diphenyl-2,5
      thienylene vinylene) is described. Unlike xanthate precursors to poly(p-phenylene
      vinylene), the thienylene vinylene analogue patterns as a positive tone resist.
      Characterization of irradiated films reveals photooxidative cleavage of the
      vinylene linker decreases the molecular weight of the polymer (increasing the
      solubility of the UV-exposed areas). As a result of the mechanism, the developed
      pattern sees no UV light exposure, which is a significant advantage compared with
      negative-tone-conjugated polymer resists. Single micron resolution of a low
      bandgap polymer is achieved in an efficient and scalable process. 

PMID- 24740900
TI  - Human prion diseases and the risk of their transmission during anatomical
      dissection.
AB  - Prion diseases (or transmissible spongiform encephalopathies) are a unique group
      of fatal progressive neurodegenerative diseases of the central nervous system.
      The infectious agent is hypothesized to consist solely of a highly protease
      resistant misfolded isoform of the host prion protein. Prions display a
      remarkable degree of resistance to chemical and physical decontamination. Many
      common forms of decontamination or neutralization used in infection control are
      ineffective against prions, except chaotropic agents that specifically disrupt
      proteins. Human cadaveric prosection or dissection for the purposes of teaching
      and demonstration of human anatomy has a distinguished history and remains one of
      the fundamentals of medical education. Iatrogenic transmission of human prion
      diseases has been demonstrated from the inoculation or implantation of human
      tissues. Therefore, although the incidence of human prion diseases is rare,
      restrictions exist upon the use of tissues from patients reported with dementia,
      specifically the brain and other central nervous system material. A current
      concern is the potential for asymptomatic variant Creutzfeldt-Jakob disease
      transmission within the UK population. Therefore, despite the preventative
      measures, the transmission of prion disease through human tissues remains a
      potential risk to those working with these materials. In this review, we aim to
      summarize the current knowledge on human prion disease relevant to those working
      with human tissues in the context of anatomical dissection.

PMID- 24740901
TI  - Exosomes and microvesicles: identification and targeting by particle size and
      lipid chemical probes.
AB  - Exosomes and microvesicles are two classes of submicroscopic vesicle released by
      cells into the extracellular space. Collectively referred to as extracellular
      vesicles, these membrane containers facilitate important cell-cell communication
      by carrying a diverse array of signaling molecules, including nucleic acids,
      proteins, and lipids. Recently, the role of extracellular vesicle signaling in
      cancer progression has become a topic of significant interest. Methods to detect
      and target exosomes and microvesicles are needed to realize applications of
      extracellular vesicles as biomarkers and, perhaps, therapeutic targets. Detection
      of exosomes and microvesicles is a complex problem as they are both
      submicroscopic and of heterogeneous cellular origins. In this Minireview, we
      highlight the basic biology of extracellular vesicles, and address available
      biochemical and biophysical detection methods. Detectible characteristics
      described here include lipid and protein composition, and physical properties
      such as the vesicle membrane shape and diffusion coefficient. In particular, we
      propose that detection of exosome and microvesicle membrane curvature with lipid
      chemical probes that sense membrane shape is a distinctly promising method for
      identifying and targeting these vesicles. 

PMID- 24740902
TI  - Clinical usefulness and cost effectiveness of fractional flow reserve among
      Indian patients (FIND study).
AB  - OBJECTIVES: To study the clinical usefulness, cost benefit, and medium term
      outcome of fractional flow reserve (FFR) based management of coronary artery
      disease of intermediate severity. BACKGROUND: In spite of the advantages of FFR
      there is paucity of data in Indian population who have frequent diffuse, small
      and multivessel disease where it would probably be more beneficial in terms of
      cost and outcome. METHODS: The treating cardiologist's management decision with
      both FFR and angiographic data was compared with that of a reviewing cardiologist
      decision based on a retrospective analysis of angiogram alone. RESULTS: Eighty
      one vessels with intermediate lesions in 59 patients required 26 stents lesser
      when FFR data was added to the angiogram. The concordance of management decision
      was about 58% which means that >40% of intermediate lesions would be
      misclassified as significant based on angiography alone. There were no major
      events at a mean follow up of 11 +/- 5 months. The net cost benefit in favor of
      FFR based management was INR 8,57,600 (USD 15,600) in our centre. CONCLUSION:
      Indians with more severe form of CAD benefit from a FFR based management plan for
      intermediate lesions, both clinically and economically. (c) 2014 Wiley
      Periodicals, Inc.

PMID- 24740903
TI  - Negative frequency-dependent preferences and variation in male facial hair.
AB  - Negative frequency-dependent sexual selection maintains striking polymorphisms in
      secondary sexual traits in several animal species. Here, we test whether
      frequency of beardedness modulates perceived attractiveness of men's facial hair,
      a secondary sexual trait subject to considerable cultural variation. We first
      showed participants a suite of faces, within which we manipulated the frequency
      of beard thicknesses and then measured preferences for four standard levels of
      beardedness. Women and men judged heavy stubble and full beards more attractive
      when presented in treatments where beards were rare than when they were common,
      with intermediate preferences when intermediate frequencies of beardedness were
      presented. Likewise, clean-shaven faces were least attractive when clean-shaven
      faces were most common and more attractive when rare. This pattern in preferences
      is consistent with negative frequency-dependent selection. 

PMID- 24740904
TI  - Red trap colour of the carnivorous plant Drosera rotundifolia does not serve a
      prey attraction or camouflage function.
AB  - The traps of many carnivorous plants are red in colour. This has been widely
      hypothesized to serve a prey attraction function; colour has also been
      hypothesized to function as camouflage, preventing prey avoidance. We tested
      these two hypotheses in situ for the carnivorous plant Drosera rotundifolia. We
      conducted three separate studies: (i) prey attraction to artificial traps to
      isolate the influence of colour; (ii) prey attraction to artificial traps on
      artificial backgrounds to control the degree of contrast and (iii) observation of
      prey capture by D. rotundifolia to determine the effects of colour on prey
      capture. Prey were not attracted to green traps and were deterred from red traps.
      There was no evidence that camouflaged traps caught more prey. For D.
      rotundifolia, there was a relationship between trap colour and prey capture.
      However, trap colour may be confounded with other leaf traits. Thus, we conclude
      that for D. rotundifolia, red trap colour does not serve a prey attraction or
      camouflage function. 

PMID- 24740905
TI  - Dermatitis herpetiformis.

PMID- 24740906
TI  - Des Spence: Narcissistic, bossy, opinionated.

PMID- 24740907
TI  - Some progress and some missed targets in the TB epidemic.

PMID- 24740908
TI  - Doctors should be taught to consider the cost of their practice.

PMID- 24740909
TI  - Three million US patients can now see their medical records online.

PMID- 24740910
TI  - EDAG positively regulates erythroid differentiation and modifies GATA1
      acetylation through recruiting p300.
AB  - Erythroid differentiation-associated gene (EDAG) has been considered to be a
      transcriptional regulator that controls hematopoietic cell differentiation,
      proliferation, and apoptosis. The role of EDAG in erythroid differentiation of
      primary erythroid progenitor cells and in vivo remains unknown. In this study, we
      found that EDAG is highly expressed in CMPs and MEPs and upregulated during the
      erythroid differentiation of CD34(+) cells following erythropoietin (EPO)
      treatment. Overexpression of EDAG induced erythroid differentiation of CD34(+)
      cells in vitro and in vivo using immunodeficient mice. Conversely, EDAG knockdown
      reduced erythroid differentiation in EPO-treated CD34(+) cells. Detailed
      mechanistic analysis suggested that EDAG forms complex with GATA1 and p300 and
      increases GATA1 acetylation and transcriptional activity by facilitating the
      interaction between GATA1 and p300. EDAG deletion mutants lacking the binding
      domain with GATA1 or p300 failed to enhance erythroid differentiation, suggesting
      that EDAG regulates erythroid differentiation partly through forming
      EDAG/GATA1/p300 complex. In the presence of the specific inhibitor of p300
      acetyltransferase activity, C646, EDAG was unable to accelerate erythroid
      differentiation, indicating an involvement of p300 acetyltransferase activity in
      EDAG-induced erythroid differentiation. ChIP-PCR experiments confirmed that GATA1
      and EDAG co-occupy GATA1-targeted genes in primary erythroid cells and in vivo.
      ChIP-seq was further performed to examine the global occupancy of EDAG during
      erythroid differentiation and a total of 7,133 enrichment peaks corresponding to
      3,847 genes were identified. Merging EDAG ChIP-Seq and GATA1 ChIP-Seq datasets
      revealed that 782 genes overlapped. Microarray analysis suggested that EDAG
      knockdown selectively inhibits GATA1-activated target genes. These data provide
      novel insights into EDAG in regulation of erythroid differentiation.

PMID- 24740911
TI  - Thermoelectric-based temperature-controlling system for in-tube solid-phase
      microextraction.
AB  - A temperature-controlling device for in-tube solid-phase microextraction was
      developed based on thermoelectric cooling and heating. This device can control
      the temperature of the capillary column from 0 to 100 degrees C by applying a
      voltage to a Peltier cooler or stainless steel tube. The extraction temperatures
      for angiotensin I, propranolol, and ranitidine were optimized. In all cases,
      setting the temperature to 10 degrees C for extraction achieved the best
      extraction efficiency. Desorption showed minimum peak broadening at 70 degrees C,
      contributing to better chromatographic performance. Propranolol was selected as a
      model compound to compare the performance of temperature-controlled in-tube solid
      phase microextraction at optimized conditions. Calibration curves exhibited good
      linearity (R(2) > 0.999) over the studied range, and the limit of detection and
      limit of quantification were about three times lower than those obtained at
      standard conditions (30 degrees C extraction and desorption). 

PMID- 24740912
TI  - The application of single-lumen endotracheal tube anaesthesia with artificial
      pneumothorax in thoracolaparoscopic oesophagectomy.
AB  - Double-lumen endotracheal tube (DLET) anaesthesia is the commonly used method in
      minimally invasive oesophagectomy (MIE). However, DLET intubation does have its
      disadvantages. Firstly, the placement of the DLET needs a skilled anaesthetist
      with familiarity of the technique and subsequent ability to perform a fibre-optic
      bronchoscopy for confirmation. Secondly, DLET intubation and one-lung ventilation
      are associated with numerous complications, including hoarseness,
      tracheobronchial injury and vocal injury. In this report, a retrospective
      analysis was performed on 42 consecutive patients who underwent MIE using single
      lumen endotracheal tube (SLET) anaesthesia with CO2 artificial pneumothorax
      compared with 81 patients who underwent the same procedure with DLET intubation.
      Our findings showed that SLET intubation with artificial pneumothorax by CO2
      insufflation is a feasible and safe method for MIE procedures. 

PMID- 24740913
TI  - Self-propelled Janus mesoporous silica nanomotors with sub-100 nm diameters for
      drug encapsulation and delivery.
AB  - The synthesis of an innovative self-propelled Janus nanomotor with a diameter of
      about 75 nm that can be used as a drug carrier is described. The Janus nanomotor
      is based on mesoporous silica nanoparticles (MSNs) with chromium/platinum
      metallic caps and propelled by decomposing hydrogen peroxide to generate oxygen
      as a driving force with speeds up to 20.2 MUm s(-1) (about 267 body lengths per
      second). The diffusion coefficient (D) of nanomotors with different H2 O2
      concentrations is calculated by tracking the movement of individual particles
      recorded by means of a self-assembled fluorescence microscope and is
      significantly larger than free Brownian motion. The traction of a single Janus
      MSN nanomotor is estimated to be about 13.47*10(-15) N. Finally, intracellular
      localization and drug release in vitro shows that the amount of Janus MSN
      nanomotors entering the cells is more than MSNs with same culture time and
      particle concentrations, meanwhile anticancer drug doxorubicin hydrochloride
      loaded in Janus MSNs can be slowly released by biodegradation of lipid bilayers
      in cells. 

PMID- 24740914
TI  - Propensity to imitate in autism is not modulated by the model's gaze direction:
      an eye-tracking study.
AB  - Individuals with Autism Spectrum Disorder (ASD) show a diminished propensity to
      imitate others' actions, as well as a diminished sensitivity and responsivity to
      others' communicative cues, such as a direct gaze. However, it is not known
      whether failure to appreciate the communicative value of a direct gaze is
      associated with imitation abnormalities in this population. In this eye-tracking
      study, we investigated how 25 preschoolers with ASD, compared with 25
      developmental and chronological age-matched children, imitate actions that are
      associated with a model's direct gaze versus averted gaze. We found that the
      model's direct gaze immediately prior to the demonstration increased the
      attention to the model and the propensity to imitate the demonstrated action in
      children without ASD. In contrast, preschoolers with ASD showed a similar
      propensity to look at the model's face and to imitate the demonstrated actions
      across the direct gaze and the averted gaze conditions. These data indicate that
      atypical imitation in ASD might be linked to abnormal processing of the model's
      communicative signals (such as a direct gaze) that modulate imitative behaviours
      in individuals without ASD. Autism Res 2014, 7: 392-399. (c) 2014 International
      Society for Autism Research, Wiley Periodicals, Inc. 

PMID- 24740922
TI  - Shape and object data analysis.
AB  - This is a discussion of the paper: 'Overview of object oriented data analysis' by
      J. Steve Marron and Andres M. Alonso. 

PMID- 24740923
TI  - Silibinin modulates caudal-type homeobox transcription factor (CDX2), an
      intestine specific tumor suppressor to abrogate colon cancer in experimental
      rats.
AB  - To authenticate the colon cancer preventive potential of silibinin, the efficacy
      of silibinin needs to be tested by evaluating an organ-specific biomarker. The
      aim of this study was to evaluate the impact of silibinin on the colonic
      expression of the caudal-type homeobox transcription factor (CDX2) an intestine
      specific tumor suppressor gene and its downstream targets in the colon of rats
      challenged with 1,2 dimethyl hydrazine (DMH). Rats of groups 1 and 2 were treated
      as control and silibinin control. Rats under groups 3 and 4 were given DMH (20
      mg/kg body weight (b.w.) subcutaneously) once a week for 15 consecutive weeks
      from the 4th week of the experimental period. In addition, group 4 rats alone
      were treated with silibinin (50 mg/kg b.w. per os) everyday throughout the study
      period of 32 weeks. Histological investigation and messenger RNA and protein
      expression studies were performed in the colonic tissues of experimental rats.
      Findings of the study revealed that DMH administration significantly decreased
      the expression of CDX2 and Guanylyl cyclase C (GCC) in the colon of experimental
      rats. Further the decreased levels of CDX2 protein, colonic mucin content, and
      increased number of mast cells in the colon of DMH alone-administered rats
      reflects the onset of carcinogenesis. The pathological changes caused due to CDX2
      suppression were attenuated by silibinin supplementation. 

PMID- 24740924
TI  - Morphing hydrogel patterns by thermo-reversible fluorescence switching.
AB  - Stimuli responsive surfaces that show reversible fluorescence switching behavior
      in response to temperature changes were fabricated. Oligo(ethylene glycol)
      methacrylate thermoresponsive polymers with amine end-groups were prepared by
      atom transfer radical polymerization (ATRP). The polymers were patterned on
      silicon surfaces by electron beam (e-beam) lithography, followed by conjugation
      of self-quenching fluorophores. Fluorophore conjugated hydrogel thin films were
      bright when the gels were swollen; upon temperature-induced collapse of the gels,
      self-quenching of the fluorophores led to significant attenuation of
      fluorescence. Importantly, the fluorescence was regained when the temperature was
      cooled. The fluorescence switching behavior of the hydrogels for up to ten cycles
      was investigated and the swelling-collapse was verified by atomic force
      microscopy. Morphing surfaces that change shape several times upon increase in
      temperature were obtained by patterning multiple stimuli responsive polymers. 

PMID- 24740925
TI  - Molecular characterization of soluble and membrane-bound trehalases in the cotton
      mirid bug, Apolygus lucorum.
AB  - Trehalose, a major hemolymph sugar in insects, is hydrolyzed by trehalase. We
      identified a soluble and a membrane-bound form of trehalase and isolated the
      corresponding mRNA, ALTre-1, and ALTre-2 in the cotton mirid bug, Apolygus
      lucorum. The deduced amino acid sequences of ALTre-1 and ALTre-2 revealed mature
      proteins with 643 and 617 amino acids, respectively. ALTre-1 and ALTre-2
      contained trehalase signature motifs, and ALTre-2 contained a putative
      transmembrane domain near the C-terminus, suggesting that ALTre-1 and ALTre-2
      encoded a soluble trehalase and a membrane-bound trehalase, respectively.
      Comparison of trehalase activity at different developmental stages and in six
      tissues indicated that soluble trehalase activity accounted for the majority of
      total trehalase activity in A. lucorum. ALTre-1 and ALTre-2 were expressed in all
      tissues and stages, with the highest expression of both in the second instar
      nymphs, ALTre-1 in the ovary and malpighian tubules, ALTre-2 in the flight
      muscles and fat body. Following the exposure of second instar nymph to 20-E, the
      soluble trehalase activity increased gradually while the membrane-bound trehalase
      activity remained at its initial level. Similarly, 20-E upregulated ALTre-1
      expression but had no effect on ALTre-2 expression. These results suggest that an
      increase of this soluble trehalase activity was upregulated by ALTre-1 gene.

PMID- 24740926
TI  - JMJD5 regulates cell cycle and pluripotency in human embryonic stem cells.
AB  - In mammalian embryos, embryonic stem cells (ESCs) and induced pluripotent cells,
      a shortened G1 phase is correlated with the pluripotent state. To molecularly
      define this phase, we compared transcripts from the shortened G1 of human ESCs
      (hESCs) with those from the longer G1 of derived endoderm. We identified JMJD5, a
      JmjC (Jumonji C) domain containing protein that, when depleted in hESCs, causes
      the accumulation of cells in G1 phase, loss of pluripotency, and subsequent
      differentiation into multiple lineages, most prominently ectoderm and
      trophectoderm. Furthermore, we demonstrate that the JMJD5 phenotype is caused by
      the upregulation of CDKN1A (p21), as depleting both JMJD5 and CDKN1A (p21) in
      hESCs restores the rapid G1 phase and rescues the pluripotent state. Overall, we
      provide genetic and biochemical evidence that the JMJD5/CDKN1A (p21) axis is
      essential to maintaining the short G1 phase which is critical for pluripotency in
      hESCs.

PMID- 24740927
TI  - cDNA cloning and transcriptional expression profiles of a hexamerin in the
      oriental fruit fly, Bactrocera dorsalis.
AB  - A Bactrocera dorsalis hexamerin (BdAr) cDNA was cloned (GenBank accession no.
      KF815528), and its transcriptional expression profiles were determined. The
      complete 2,530-bp cDNA encodes a 780-amino acid protein with a predicted
      molecular mass of 94.01 kDa. The proportions of phenylalanine (7.8%), tyrosine
      (11.2%), and methionine (2.6%) in BdAr as well as all other amino acids are
      reported. BdAr transcripts were detected in the brain, flight muscle, foregut,
      Malpighian tubules, and fat body. In the larval stage, BdAr transcripts were
      expressed in the early third instar and increased in the late third instar. In
      pupae, the highest expression of BdAr mRNA was present on day 1, then declined
      and persisted through day 2 to day 8. In adult females, the relative expression
      of BdAr was significantly higher on day 0 and day 1 compared to day 6 to day 10
      while it was highest in newly eclosed adult males. The comparison of the BdAr
      expression between 8-10-day-old males and females showed a higher level in
      females. Our phylogenetic analysis results suggest to us that BdAr is similar to
      Drosophila larval serum protein 1gamma.

PMID- 24740928
TI  - Highly stretchable transistors using a microcracked organic semiconductor.

PMID- 24740929
TI  - Drowning.

PMID- 24740931
TI  - Passing the torch.

PMID- 24740932
TI  - Logrank-type tests with presmoothing.
AB  - The logrank test is the most popular choice for testing the equality of two
      survival distributions with time-to-event data. It is based on the comparison of
      the Nelson-Aalen estimates of the corresponding cumulative hazard functions. The
      improvements of the logrank test in the literature have been accomplished using
      weighted logrank tests, with the weight chosen appropriately to maximize power.
      Notwithstanding, power also depends on the efficiency of the estimation of the
      cumulative hazard function. The presmoothed estimator has been shown to be more
      efficient than the Nelson-Aalen estimator under some general assumptions. We
      introduce a new logrank-type test that, instead of the Nelson-Aalen estimator, is
      based on its presmoothed counterpart. An extensive simulation study has been
      conducted to compare the performance of this new test with the classical one.
      This study shows that the new test has the proper size under the null hypothesis,
      while improving the power over a wide range of alternatives. The new test is
      illustrated with several real data examples. 

PMID- 24740933
TI  - TRF2-mediated stabilization of hREST4 is critical for the differentiation and
      maintenance of neural progenitors.
AB  - Telomere repeat binding factor 2 (TRF2) is a component of the shelterin complex
      that is known to bind and protect telomeric DNA, yet the detection of TRF2 in
      extra-telomeric regions of chromosomes suggests other roles for TRF2 besides
      telomere protection. Here, we demonstrate that TRF2 plays a critical role in
      antagonizing the repressive function of neuron-restrictive silencer factor, also
      known as repressor element-1 silencing transcription factor (REST), during the
      neural differentiation of human embryonic stem cells (hESCs) by enhancing the
      expression of a truncated REST splice isoform we term human REST4 (hREST4) due to
      its similarity to rodent REST4. We show that TRF2 is specifically upregulated
      during hESC neural differentiation concordantly with an increase in the
      expression of hREST4 and that both proteins are highly expressed in NPCs.
      Overexpression of TRF2 in hESCs increases hREST4 levels and induces their neural
      differentiation, whereas TRF2 knockdown in hESCs and NPCs reduces hREST4
      expression, hindering their ability to differentiate to the neural lineage.
      Concurrently, we show that TRF2 directly interacts with the C-terminal of hREST4
      through its TRF2 core binding motif [F/Y]xL, protecting hREST4 from ubiquitin
      mediated proteasomal degradation and consequently furthering neural induction.
      Thus, the TRF2-mediated counterbalance between hREST4 and REST is vital for both
      the generation and maintenance of NPCs, suggesting an important role for TRF2 in
      both neurogenesis and function of the central nervous system.

PMID- 24740934
TI  - An original device for intraoperative detection of small indeterminate nodules?.
AB  - OBJECTIVES: The purpose of this study was to evaluate the efficiency of our newly
      designed tactile mechanoreceptor in detection of pulmonary lesions during
      thoracoscopy. METHODS: Twenty-seven patients with peripheral undetermined
      subpleural solitary pulmonary lesions detected on computed tomography were
      included in a prospective non-randomized trial. All nodules from 7 to 18 mm in
      diameter were located deep in the lung parenchyma (>= 10 mm from the lung
      surface). All patients underwent thoracoscopic exploration with diagnostic
      intent. Instrumental palpation with lung forceps was performed first, followed by
      thorough inspection of lung tissue with the tactile mechanoreceptor. This device
      is a metal tube 10 mm in diameter, which can be inserted into the pleural cavity
      via a standard 10-mm port. There is an elastic membrane on its working end, which
      deforms greatly if the palpated tissue has greater density. Intraoperatively, the
      surgeon pushed the targeted region of pulmonary tissue with the mechanoreceptor
      and carried out the measurement. The density of tissue characteristics was
      displayed with special software using colour change in real time. After detection
      of a pulmonary nodule, it was resected with endostaplers. RESULTS: Instrumental
      palpation was successful in detection of pulmonary lesions in 10 (37%) patients
      and was confirmed with the tactile mechanoreceptor. In 12 (44%) patients,
      instrumental palpation failed to locate an intrapulmonary nodule, while the
      tactile mechanoreceptor facilitated finding the lesion and performing
      thoracoscopic lung resection in all these patients. Intraoperative histological
      examination confirmed benign disease in 8, metastatic lesion in 12 and primary
      lung cancer in 7 patients requiring thoracoscopic lobectomy. In 5 (19%) patients,
      neither forceps nor the tactile mechanoreceptor was able to detect any pulmonary
      lesion, necessitating mini-thoracotomy for finger palpation. The overall efficacy
      of the tactile mechanoreceptor in detection of pulmonary lesions was 81%, and of
      impalpable nodes 71%. CONCLUSIONS: The tactile mechanoreceptor is an effective
      tool for detection of impalpable pulmonary lesions during thoracoscopy.

PMID- 24740935
TI  - Pulsatile cardiopulmonary bypass and renal function in elderly patients
      undergoing aortic valve surgery?.
AB  - OBJECTIVES: To evaluate if pulsatile cardiopulmonary bypass (CPB) has any
      protective influence on renal function in elderly patients undergoing aortic
      valve replacement (AVR). METHODS: Forty-six patients (>= 75 years old) with
      aortic valve stenosis underwent AVR with either pulsatile perfusion (PP) or non
      pulsatile perfusion (NP) during CPB. Haemodynamic efficacy of the blood pump
      during either type of perfusion was described in terms of the energy equivalent
      pressure and the surplus haemodynamic energy. Urine samples were collected before
      surgery, at sternum closure, and at 2 and 18 h of intensive care unit stay to
      detect acute kidney injury markers. Perioperative urine levels of N-acetyl-beta-D
      glucosaminidase (NAG), kidney injury molecule-1 and neutrophil gelatinase
      associated lipocalin (NGAL) were assessed together with plasma creatinine,
      creatinine clearance (CCr) and 24-h haemodynamic monitoring. Normally distributed
      continuous variables were described as mean +/- standard deviation and non
      normally distributed data were presented as the median [25th-75th percentiles].
      RESULTS: PP was characterized by a significantly higher amount of surplus
      haemodynamic energy transferred to the patients (P < 0.001), with lower mean
      systemic vascular resistance during CPB (P = 0.020) and during 18 h
      postoperatively (group-P = 0.018). No difference was found between pre- and
      postoperative CCr in the PP group (71 +/- 23 vs 60 +/- 35 ml/min, P = 0.27),
      while its statistically significant perioperative decrement was observed in the
      NP group (67 +/- 24 vs 45 +/- 15 ml/min, P < 0.001). The PP group showed
      significantly lower urinary levels of NAG at 18 h postoperatively (P = 0.008),
      and NGAL at sternum closure (P = 0.010), 2 h (P < 0.001) and 18 h (P = 0.015)
      postoperatively. CONCLUSIONS: Short-term PP in elderly patients showed higher
      safety for renal physiology than NP, resulting in better maintenance of
      glomerular filtration and lower renal tissue injury.

PMID- 24740936
TI  - Extracorporeal membrane oxygenation support for complex tracheo-bronchial
      procedures?.
AB  - OBJECTIVES: The published experience with advanced broncho-plastic procedures
      performed with extracorporeal membrane oxygenation (ECMO) support is very
      limited. We examined our results to assess the risks and benefits of this
      approach. METHODS: We retrospectively analysed all patients with thoracic
      malignancies who underwent complex tracheo-bronchial reconstruction under ECMO
      support in our department between 2001 and 2013. RESULTS: Ten patients (age range
      21-81 years, mean 54 +/- 11 years) underwent complex tracheo-bronchial
      reconstructions under veno-arterial ECMO support. In 7 patients, the underlying
      pathology was non-small-cell lung cancer, in 2 cases carcinoid tumour and in 1
      case adenoid cystic carcinoma. ECMO cannulation was central (n = 7) or peripheral
      (n = 3). Mean time on bypass was 113 +/- 17 min (range 70-135 min). A complete
      resection (R0) was achieved in 8 patients (80%). There was no perioperative
      mortality. Patients were discharged from the hospital after 7-52 days (median 11
      days). Median time on ICU was 1 day (range 1-36 days). There was no complication
      related to the use of ECMO in this series. Mean follow-up time was 1694 +/- 1385
      days (range 12-4338). The 1-, 3- and 5-year Kaplan-Meier survival was 100, 74 and
      56%, respectively. CONCLUSIONS: Based on this experience, we consider veno
      arterial ECMO support as a safe and valuable approach for complex airway surgery.

PMID- 24740937
TI  - Examining the relationship between the prevalence of guns and homicide rates in
      the USA using a new and improved state-level gun ownership proxy.
AB  - Determining the relationship between gun ownership levels and firearm homicide
      rates is critical to inform public health policy. Previous research has shown
      that state-level gun ownership, as measured by a widely used proxy, is positively
      associated with firearm homicide rates. A newly developed proxy measure that
      incorporates the hunting license rate in addition to the proportion of firearm
      suicides correlates more highly with state-level gun ownership. To corroborate
      previous research, we used this new proxy to estimate the association of state
      level gun ownership with total, firearm, and non-firearm homicides. Using state
      specific data for the years 1981-2010, we modelled these rates as a function of
      gun ownership level, controlling for potential confounding factors. We used a
      negative binomial regression model and accounted for clustering of observations
      among states. We found that state-level gun ownership as measured by the new
      proxy, is significantly associated with firearm and total homicides but not with
      non-firearm homicides. 

PMID- 24740939
TI  - Integrity in publication.

PMID- 24740940
TI  - Theoretical thinking on suffering.
AB  - This is an introduction to the column on the Concept Inventing of Sufferance.

PMID- 24740941
TI  - Concept inventing: a humanbecoming perspective on suffering.
AB  - Sufferance is a universal living experience. In view of the humanbecoming
      theoretical perspective, concept inventing is a way to expand understanding about
      a phenomenon of interest and to contribute to nursing knowledge development. This
      column offers a synthetic definition of sufferance in light of the concept
      inventing process. Sufferance is anguishing turbulence in weaving the cherished
      arising with luminous shifting. At the theoretical level, sufferance is imaging
      in the valuing connecting-separating of transforming. 

PMID- 24740942
TI  - The mentor-mentee relationship: an intricate dance.
AB  - Leadership in the mentoring of novice researchers is the focus of this column.
      Interviews with two senior nurse research scientists is presented in which they
      respond to questions about the nature of mentoring, advantages and disadvantages
      of the process for both the mentor and the mentee, and the necessary factors for
      a good mentoring relationship. Both scientists discuss their on-going work in
      mentoring and finally a synopsis of their thoughts is presented. 

PMID- 24740943
TI  - Stewardship and leadership in nursing.
AB  - The concept or metaphor of stewardship is important to the future of the
      discipline of nursing. Nurse leaders and scholars of the discipline are entrusted
      to preserve and hold in trust the value priorities of the discipline as well as
      the value priorities of others who are living health. The author here offers a
      discussion of possible meanings and ethical implications for enhancing the
      discipline's potential obligations of leadership and stewardship as a basic human
      science discipline. 

PMID- 24740944
TI  - Honoring silence and valuing community: living leadership in 21st century
      teaching-learning.
AB  - Leadership is a very personal concept. The methods implemented by leaders often
      reflect philosophical beliefs and theoretical underpinnings. This column, while
      recognizing that leadership styles are indeed personal, proffers living
      leadership in nursing education through two key leadership attitudes. These
      attitudes are honoring silence and valuing community. Honoring silence is
      discussed as recognizing the multiple dimensions of silence, and valuing
      community is presented in light of the humanbecoming community models change
      concepts: moving-initiating, anchoring-shifting, and pondering-shaping. 

PMID- 24740945
TI  - A case for nursing theory in practice.
AB  - The discipline of nursing is on a slippery slope with regard to the ever
      increasing lack of nursing theory in its work. The misguided attempt to eliminate
      the use of nursing theory as the underpinning of practice is degrading nursing as
      a viable profession, ultimately affecting patient care. A clarion call to the
      discipline regarding the need for theory in research and practice is required.
      Nursing will soon become just another set of tasks rather than the profession
      needed by patients and their families. 

PMID- 24740946
TI  - Conceptualizations of health in nursing practice.
AB  - There are many ways of living health as individuals describe it from unique
      perspectives. With the intent of serving others, healthcare professionals rely on
      a specific conceptualization of health consistent with a practice methodology.
      Hence, for the advancement of innovative scientific knowledge health can be
      viewed from distinct paradigmatic perspectives and must be founded on a congruent
      ontological-epistemological-methodological link in professional practice. The
      purpose of this column is to describe conceptualizations of health with congruent
      practice methodologies from three distinct nursing paradigmatic perspectives. The
      authors consider that these distinct paradigmatic nursing perspectives offer
      diverse disciplinary knowledge of social utility to nursing professional practice
      for the betterment of the ones being served. 

PMID- 24740947
TI  - Transformative leadership based on nursing science.
AB  - The dialogue for this column is a summary of a dialogue among two preeminent
      nursing scholars and myself that took place "live" at the 40th Meeting of the
      American Academy of Nursing, focused on transforming healthcare. The dialogue was
      recorded and transcribed verbatim. In editing the dialogue I tried to leave it
      conversational which was the nature of the interaction. The paper that follows
      reflects the thinking of two executive nurse leaders who use different nursing
      frameworks as the basis for their practice. Translation of their practice models
      to leadership is presented as a natural transition to transformation.

PMID- 24740948
TI  - A humanbecoming qualitative descriptive study on quality of life with older
      adults.
AB  - Quality of life is a universal living experience and is significant for older
      adults living in long-term residential care facilities. The purposes of this
      research study were to: explicate the experience of quality of life for older
      adults, contribute to the understanding of quality of life for older adults and
      to nursing's extant body of knowledge by enhancing humanbecoming. Humanbecoming
      was selected as the theoretical perspective for the qualitative descriptive
      exploratory method study with 10 volunteers living in the same long-term
      residential care facility in Singapore. Findings showed that: quality of life is
      fortifying tranquillity amid potential turbulence with the gratifying engagements
      of diverse affiliations, as envisioning possibilities arise with discordant
      constraints. The findings of this study have made a significant contribution to
      the phenomenon - quality of life both in terms of older adults living in nursing
      homes and from a Singaporean context. 

PMID- 24740949
TI  - Care delivery for Filipino Americans using the Neuman systems model.
AB  - Filipino Americans are at risk of coronary heart disease due to the presence of
      multiple cardiometabolic factors. Selecting a framework that addresses the
      factors leading to coronary heart disease is vital when providing care for this
      population. The Neuman systems model is a comprehensive and wholistic framework
      that offers an innovative method of viewing clients, their families, and the
      healthcare system across multiple dimensions. Using the Neuman systems model,
      advanced practice nurses can develop and implement interventions that will help
      reduce the potential cardiovascular problems of clients with multiple risk
      factors. The authors in this article provides insight into the cardiovascular
      health of Filipino Americans and has implications for nurses and other healthcare
      providers working with various Southeast Asian groups in the United States. 

PMID- 24740950
TI  - Developing a model: an illustration.
AB  - Model development may seem a daunting task for the novice. The purpose of this
      article is to illustrate the steps of model development applied to a real-life
      phenomenon using an inductive theory-generating research approach. The value of
      the illustration is that nurse researchers can follow the application of the
      process as a point of departure for their own work. A logical stepwise discussion
      is followed for empirical theory development. The logical thought process from
      identifying the phenomenon to describing the model as a visual metaphor of the
      phenomenon is illustrated. 

PMID- 24740951
TI  - Presence with scenario-based high fidelity human patient simulation.
AB  - The aim of this grounded theory study was to explain the nature of presence among
      nursing students participating in scenario-based high fidelity human patient
      simulation. Data were derived from observations and interviews with 145
      participants. Among participants, presence was found to be a multidimensional,
      dynamic interaction characterized by a centricity between the simulation and the
      natural environment. Presence, the core concept from the explanatory model that
      emerged from this study, is delineated in this article. Presence centricity in
      simulation may impact the learning experience and outcomes. These study results
      may support development of the educational science related to clinical
      simulation. 

PMID- 24740952
TI  - Stories from Haiti: a comparison of three approaches.
AB  - Two stories from Haiti are considered from three different perspectives. The
      first story is about a boy named Joseph Alvyns, whose mother died from cholera in
      2011. His story is told in a short film titled Baseball in the time of Cholera.
      The second story is about Mme. Yolande Marie Nazaire, who was the Director of the
      Haiti National School of Nursing in Port-au-Prince on the morning of January 12,
      2010, when an earthquake killed 90 students and faculty. The three perspectives
      discussed here are: (a) Critical Reflective in health professional education as
      used by the University of California at San Francisco (UCSF) School of Medicine;
      (b) The Capacities of Stories, which is part of a socio-narratology methodology;
      and(c) Story Theory with implications for global health nursing. 

PMID- 24740953
TI  - A unitary transformative perspective on transformational leadership.
AB  - This is an introduction to Turkel's contemporary transformational leadership
      article. 

PMID- 24740954
TI  - Leading from the heart: caring, love, peace, and values guiding leadership.
AB  - Contemporary transformational leadership focuses on authentic leadership styles,
      relational caring, meaningful recognition, creativity, building trust,
      relationships, participative decision making, dialogue with time for reflection,
      and innovation. The purpose of this paper is to illuminate how concepts from the
      unitary transformative paradigm and caring science can be integrated within
      nursing leadership practice, to invite nurse leaders to make these concepts
      explicit in their own transformational leadership journey, and to offer ways of
      reframing traditional organizational language. Practice exemplars are presented
      to highlight how tenets from caring theory are guiding the practice of nursing
      leadership. 

PMID- 24740955
TI  - Thoughts about interprofessional education.
AB  - This essay is about two views of interprofessional education. One view emphasizes
      the coming together of students of various healthcare areas to learn about each
      other's roles and role activities. The other view focuses on the meaning of
      "inter" as the blurring of boundaries among healthcare areas with the potential
      of loss of distinct roles and role activities and evolution to a single
      healthcare profession. 

PMID- 24740958
TI  - A response to the editorial "Move over nurses: there's a new professional on the
      block.".

PMID- 24740959
TI  - Bioinspired nanoscale materials for biomedical and energy applications.
AB  - The demand for green, affordable and environmentally sustainable materials has
      encouraged scientists in different fields to draw inspiration from nature in
      developing materials with unique properties such as miniaturization, hierarchical
      organization and adaptability. Together with the exceptional properties of
      nanomaterials, over the past century, the field of bioinspired nanomaterials has
      taken huge leaps. While on the one hand, the sophistication of hierarchical
      structures endows biological systems with multi-functionality, the synthetic
      control on the creation of nanomaterials enables the design of materials with
      specific functionalities. The aim of this review is to provide a comprehensive,
      up-to-date overview of the field of bioinspired nanomaterials, which we have
      broadly categorized into biotemplates and biomimics. We discuss the application
      of bioinspired nanomaterials as biotemplates in catalysis, nanomedicine,
      immunoassays and in energy, drawing attention to novel materials such as protein
      cages. Furthermore, the applications of bioinspired materials in tissue
      engineering and biomineralization are also discussed. 

PMID- 24740961
TI  - Creating gecko-like adhesives for "real world" surfaces.

PMID- 24740962
TI  - Regarding human cytomegalovirus in neuroblastoma.
AB  - Wolmer-Solberg et al., reported that six human neuroblastoma cell lines and the
      vast majority of clinical neuroblastoma samples contained HCMV DNA and expressed
      HCMV proteins. We could not replicate the data and therefore remain skeptical
      towards the prevalence of HCMV DNA in neuroblastomas.

PMID- 24740963
TI  - Development of a culturally relevant consumer health information website for
      Harlem, New York.
AB  - The process of creating a geographically tailored health information website with
      ongoing feedback from community members is one of inquiry and discovery,
      frustration and triumph, and development and reevaluation. This article reviews
      the development and implementation of GetHealthyHarlem.org, a health literacy
      level-appropriate consumer health information website tailored to consumers in
      Harlem, New York City. From 2004 to 2009, the Harlem Health Promotion Center, one
      of 37 Prevention Research Centers in the United States, sought to determine the
      use and seeking of online health information in Harlem, New York City in order to
      further explore the possibility of providing online health information to this
      community. Specifically, this article details how we sought to identify gaps,
      concerns, and uses of online health information and health care seeking in this
      local, predominantly racial and ethnic minority population. We review how we
      identified and addressed the multitude of variables that play a role in
      determining the degree of success in finding and using online health information,
      and include discussions about the genesis of the website and our successes and
      challenges in the development and implementation stages. 

PMID- 24740964
TI  - Stepping up to the challenge: the development, implementation, and assessment of
      a statewide, regional, leadership program for school nutrition directors.
AB  - A statewide professional development program was developed and implemented
      throughout California for school nutrition directors with the goal of creating
      healthy school environments and regional networks for collaboration and healthy
      school environment sustainability. Needs of school nutrition directors were
      identified through a needs assessment questionnaire. Results of the needs
      assessment questionnaire (n = 256) identified (a) planning cost-effective menus;
      (b) reducing calories, sodium, saturated fat, and trans fat in menus; and (c)
      using U.S. Department of Agriculture foods cost-effectively as the most useful
      topics. Highest rated topics informed the content of the professional development
      program. A post-professional development questionnaire identified key "insights,
      inspirations, and strategies" as (a) marketing of school foods program, (b)
      expansion of salad bars, and (c) collaboration with community partners. A 6-month
      follow-up questionnaire identified that 86% of participants made progress toward
      implementing at least one of their five insights, inspirations, and strategies in
      their school districts. Most common areas that were implemented were marketing
      and branding (32%), revamping salad bars (18%), and motivating staff (16%).
      School and Community Actions for Nutrition survey analysis showed a significant
      increase in the use of marketing methods in school nutrition programs from
      baseline to 6-month post-program implementation (p = .024). 

PMID- 24740965
TI  - Expanded coverage under US health act projected to cost $104bn less than
      expected.

PMID- 24740960
TI  - From local structure to a global framework: recognition of protein folds.
AB  - Protein folding has been a major area of research for many years. Nonetheless,
      the mechanisms leading to the formation of an active biological fold are still
      not fully apprehended. The huge amount of available sequence and structural
      information provides hints to identify the putative fold for a given sequence.
      Indeed, protein structures prefer a limited number of local backbone
      conformations, some being characterized by preferences for certain amino acids.
      These preferences largely depend on the local structural environment. The
      prediction of local backbone conformations has become an important factor to
      correctly identifying the global protein fold. Here, we review the developments
      in the field of local structure prediction and especially their implication in
      protein fold recognition. 

PMID- 24740966
TI  - Hyparrhenia hirta: A potential protective agent against hematotoxicity and
      genotoxicity of sodium nitrate in adult rats.
AB  - The present study was carried out to examine the adverse hematotoxic and
      genotoxic effects of water nitrate pollution on male adult rats and the use of
      hyparrhenia hirta methanolic extract in alleviating these effects. Sodium nitrate
      (NaNO3 ) was administered to adult rats by oral gavage at a dose of 400 mg kg(-1)
      bw daily for 50 days, while hyparrhenia hirta methanolic extract was given by
      drinking water at a dose of 1.5 mg mL(-1) (200 mg kg(-1) bw). The NaNO3 -treated
      group showed a significant decrease in red blood cell count, hemoglobin and
      hematocrit and a significant increase in total white blood cell, in neutrophil
      and eosinophil counts. Platelet count, mean corpuscular volume, mean corpuscular
      hemoglobin, and mean corpuscular hemoglobin concentration remained unchanged in
      treated groups compared to those of controls. Meanwhile, the results showed a
      marked reduction in the antioxidant enzyme activities, such as superoxide
      dismutase, catalase, and glutathione peroxidase, along with an elevation in the
      level of lipid peroxidation and a reduction in the total glutathione content,
      indicating the induction of oxidative stress in the erythrocytes of NaNO3 
      treated group. Interestingly, NaNO3 treatment showed a significant increase in
      the frequencies of total chromosomal aberrations, aberrant metaphases and
      micronucleus in bone-marrow cells. The oxidative stress induced by nitrate
      treatment might be the major cause for chromosomal rearrangements as free
      radicals leading to DNA damage. Hyparrhenia hirta methanolic extract appeared to
      be effective against hematotoxic and genotoxic changes induced by nitrate, as
      evidenced by the improvement of the markers cited above.

PMID- 24740967
TI  - Single-crystalline tungsten oxide quantum dots for fast pseudocapacitor and
      electrochromic applications.

PMID- 24740968
TI  - Outcomes after (90) Yttrium-ibritumomab tiuxetan-BEAM in diffuse large B-cell
      lymphoma: a meta-analysis.
AB  - High-dose chemotherapy followed by autologous stem cell transplantation (ASCT) is
      a standard therapy in patients with relapsed/refractory diffuse large B-cell
      lymphoma (DLBCL) who are chemosensitive. The combination of carmustine,
      etoposide, cytarabine, and melphalan (BEAM) is commonly used as a conditioning
      regimen. The addition of yttrium-90 ((90) Y)-ibritumomab tiuxetan (Zevalin((r)))
      to BEAM (Z-BEAM) is increasingly being used to improve outcomes and overcome
      refractory disease. We conducted a literature review and meta-analysis in order
      to evaluate the clinical effects of Z-BEAM followed by ASCT in patients with
      DLBCL. A literature search was conducted for randomized controlled trials and
      observational studies of Z-BEAM as a conditioning regimen for ASCT in adult
      patients with DLBCL. Extracted data included baseline patient demographics,
      overall response (ORR), complete response (CR), overall survival (OS),
      progression-free survival (PFS), nonrelapse mortality (NRM), median time to ANC
      and platelet engraftment, and rate of myelodysplastic syndrome. Mixed-effects
      models were used to determine estimates. Ten studies (N = 328) were included in
      the meta-analysis. The 2-year OS and PFS were 84.5% (n = 328) and 67.2% (n =
      285), respectively. Outcomes were superior in patients with nontransformed
      lymphoma. Posttransplant, ORR and CR rates were 72.6% and 68.5%, respectively.
      The NRM rate was 6.3% and the incidence rate of myelodysplastic syndrome was
      2.5%. Two-year OS was significantly associated with pretransplant ORR (P = 0.008,
      tau(2) = 0). There was no significant association between PFS and pretransplant
      response. Z-BEAM is safe and effective as a conditioning regimen in
      relapsed/refractory DLBCL.

PMID- 24740970
TI  - Correction: Strong inter-population cooperation leads to partner intermixing in
      microbial communities.

PMID- 24740969
TI  - Subcellular and supracellular mechanical stress prescribes cytoskeleton behavior
      in Arabidopsis cotyledon pavement cells.
AB  - Although it is a central question in biology, how cell shape controls
      intracellular dynamics largely remains an open question. Here, we show that the
      shape of Arabidopsis pavement cells creates a stress pattern that controls
      microtubule orientation, which then guides cell wall reinforcement. Live-imaging,
      combined with modeling of cell mechanics, shows that microtubules align along the
      maximal tensile stress direction within the cells, and atomic force microscopy
      demonstrates that this leads to reinforcement of the cell wall parallel to the
      microtubules. This feedback loop is regulated: cell-shape derived stresses could
      be overridden by imposed tissue level stresses, showing how competition between
      subcellular and supracellular cues control microtubule behavior. Furthermore, at
      the microtubule level, we identified an amplification mechanism in which
      mechanical stress promotes the microtubule response to stress by increasing
      severing activity. These multiscale feedbacks likely contribute to the robustness
      of microtubule behavior in plant epidermis. DOI:
      http://dx.doi.org/10.7554/eLife.01967.001. 

PMID- 24740971
TI  - Epidermal growth factor-like domain 7 is a marker of the endothelial lineage and
      active angiogenesis.
AB  - Epidermal growth factor-like domain 7 (Egfl7) expression in the developing embryo
      is largely restricted to sites of mesodermal progenitors of
      angioblasts/hemangioblasts and the vascular endothelium. We hypothesize that
      Egfl7 marks the endothelial lineage during embryonic development, and can be used
      to define the emergence of endothelial progenitor cells, as well as to visualize
      newly-forming vasculature in the embryo and during the processes of physiologic
      and pathologic angiogenesis in the adult. We have generated a transgenic mouse
      strain that expresses enhanced green fluorescent protein (eGFP) under the control
      of a minimal Egfl7 regulatory sequence (Egfl7:eGFP). Expression of the transgene
      recapitulated that of endogenous Egfl7 at sites of vasculogenesis and
      angiogenesis in the allantois, yolk sac, and in the embryo proper. The transgene
      was not expressed in the quiescent endothelium of most adult organs. However, the
      uterus and ovary, which undergo vascular growth and remodeling throughout the
      estrus cycle, expressed high levels of Egfl7:eGFP. Importantly, expression of the
      Egfl7:eGFP transgene was induced in adult neovasculature. We also found that
      increased Egfl7 expression contributed to pathologic revascularization in the
      mouse retina. To our knowledge, this is the first mouse model that enables
      monitoring of endothelial cells at sites of active vasculogenesis and
      angiogenesis. This model also facilitated the isolation and characterization of
      EGFL7(+) endothelial cell populations by fluorescence activated cell sorting
      (FACS). Together, our results demonstrate that the Egfl7:eGFP reporter mouse is a
      valuable tool that can be used to elucidate the mechanisms by which blood vessels
      form during development and under pathologic circumstances.

PMID- 24740972
TI  - The combination of weekly trastuzumab plus vinorelbine may be preferable regimen
      in HER-2 positive breast cancer patients with brain metastasis.
AB  - Brain metastasis is one of the most important life-threatening conditions in
      patients with metastatic HER-2 positive breast cancer. A lot of conventional
      chemotherapeutic and antibody-based regimens used routinely in treatment of the
      patients with breast cancer are not effective due to blood-brain barrier. In our
      cases, we reported on three HER-2 positive breast cancer patients with brain
      metastasis who were offered a combination of weekly trastuzumab plus vinorelbine
      after brain metastasis. In our cases, the progression-free survival were 12, 16
      and 9 months for Case 1, Case 2 and Case 3, respectively. In Case 1, there was no
      progression in the brain. In Case 3, we did not detect any progress but the
      patient died due to cerebrovascular embolic events. After local treatment, the
      combination of weekly trastuzumab plus vinorelbine may be an effective
      alternative regimen in HER-2 positive breast cancer patients with brain
      metastases. 

PMID- 24740973
TI  - Environmental scan of anal cancer screening practices: worldwide survey results.
AB  - Anal squamous cell carcinoma is rare in the general population but certain
      populations, such as persons with HIV, are at increased risk. High-risk
      populations can be screened for anal cancer using strategies similar to those
      used for cervical cancer. However, little is known about the use of such
      screening practices across jurisdictions. Data were collected using an online
      survey. Health care professionals currently providing anal cancer screening
      services were invited to complete the survey via email and/or fax. Information
      was collected on populations screened, services and treatments offered, and
      personnel. Over 300 invitations were sent; 82 providers from 80 clinics around
      the world completed the survey. Fourteen clinics have each examined more than
      1000 patients. Over a third of clinics do not restrict access to screening; in
      the rest, eligibility is most commonly based on HIV status and abnormal anal
      cytology results. Fifty-three percent of clinics require abnormal anal cytology
      prior to performing high-resolution anoscopy (HRA) in asymptomatic patients.
      Almost all clinics offer both anal cytology and HRA. Internal high-grade anal
      intraepithelial neoplasia (AIN) is most often treated with infrared coagulation
      (61%), whereas external high-grade AIN is most commonly treated with imiquimod
      (49%). Most procedures are performed by physicians, followed by nurse
      practitioners. Our study is the first description of global anal cancer screening
      practices. Our findings may be used to inform practice and health policy in
      jurisdictions considering anal cancer screening. 

PMID- 24740974
TI  - Thiolated eudragit-based nanoparticles for oral insulin delivery: preparation,
      characterization, and evaluation using intestinal epithelial cells in vitro.
AB  - This work deals with the synthesis of insulin loaded nanoparticles (NPs) composed
      of thiolated Eudragit L100 (Eul-cys) and reduced glutathione (GSH) as potential
      nanocarriers for oral delivery of insulin. Perfectly spherical NPs with an
      average particle size of nearly 200-300 nm are prepared. The insulin release from
      Eul-cys/GSH and Eul-cys NPs in PBS (pH 7.4) shows that GSH can slightly decrease
      the release rate of insulin. Eul-cys in combination with GSH or sodium caprate
      (SC) is evaluated for its permeation enhancing effect of FITC-insulin using the
      Caco-2 monolayer and Caco-2/HT29-MTX co-cultured cells models. SC results in
      greater permeation enhancement compared to GSH. However, GSH proves to be less
      toxic. Paracellular transport of insulin represents the main mechanism by which
      the NPs facilitate insulin permeation through the intestinal epithelium, whereas
      a number of NPs are also taken up by the cells and release insulin within the
      cells. 

PMID- 24740975
TI  - Elements of patient-health-care provider communication related to cardiovascular
      rehabilitation referral.
AB  - Cardiovascular rehabilitation has been designed to decrease the burden of
      cardiovascular disease. This study described (1) patient-health-care provider
      interactions regarding cardiovascular rehabilitation and (2) which discussion
      elements were related to patient referral. This was a prospective study of
      cardiovascular patients and their health-care providers. Discussion utterances
      were coded using the Roter Interaction Analysis System. Discussion between 26
      health-care providers and 50 patients were recorded. Cardiovascular
      rehabilitation referral was related to greater health-care provider interactivity
      (odds ratio = 2.82, 95% confidence interval = 1.01-7.86) and less patient concern
      and worry (odds ratio = 0.64, 95% confidence interval = 0.45-0.89). Taking time
      for reciprocal discussion and allaying patient anxiety may promote greater
      referral. 

PMID- 24740976
TI  - Surface structure influences contact killing of bacteria by copper.
AB  - Copper kills bacteria rapidly by a mechanism that is not yet fully resolved. The
      antibacterial property of copper has raised interest in its use in hospitals, in
      place of plastic or stainless steel. On the latter surfaces, bacteria can survive
      for days or even weeks. Copper surfaces could thus provide a powerful accessory
      measure to curb nosocomial infections. We here investigated the effect of the
      copper surface structure on the efficiency of contact killing of Escherichia
      coli, an aspect which so far has received very little attention. It was shown
      that electroplated copper surfaces killed bacteria more rapidly than either
      polished copper or native rolled copper. The release of ionic copper was also
      more rapid from electroplated copper compared to the other materials. Scanning
      electron microscopy revealed that the bacteria nudged into the grooves between
      the copper grains of deposited copper. The findings suggest that, in terms of
      contact killing, more efficient copper surfaces can be engineered. 

PMID- 24740977
TI  - Amyotrophic lateral sclerosis and parkinsonism in Papua, Indonesia: 2001-2012
      survey results.
AB  - OBJECTIVE: Only one previous follow-up study of amyotrophic lateral sclerosis
      (ALS) and parkinsonism in Papua, Indonesia has been carried out since a survey
      undertaken in 1962-1981 by Gajdusek and colleagues. Therefore, to clarify the
      clinical epidemiology of ALS and parkinsonism in the southern coastal region of
      Papua, the clinical characteristics and prevalence of the diseases in this region
      were examined and assessed. METHODS: Cases of ALS and parkinsonism were
      clinically examined during a 2001-2012 survey in Bade and other villages along
      the Ia, Edera, Dumut and Obaa rivers in Papua, Indonesia. Possible, probable and
      definite ALS was diagnosed clinically by certified neurologists based on El
      Escorial criteria. The criteria for a diagnosis of parkinsonism were the presence
      of at least two of the four following signs: tremor, rigidity, bradykinesia and
      postural impairment with a progressive course. RESULTS: During the survey, 46
      cases of ALS and/or parkinsonism were diagnosed within a population range of 7000
      (2001-2002) to 13 900 (2007-2012). The 46 cases consisted of 17 probable-definite
      cases of ALS, including three with cognitive impairment (CI), 13 cases of
      overlapping possible, probable or definite ALS and parkinsonism, including five
      with CI, and 16 cases of parkinsonism, including one with CI. The crude point
      prevalence rate of pure ALS was estimated to be at least 73 (95% CI 0 to 156) to
      133 (27 to 240)/100 000 people and that of overlapping ALS and parkinsonism at
      least 53 (0 to 126) to 98 (2 to 193)/100 000 in 2007, or 2010 in some regions.
      CONCLUSIONS: While the prevalence of ALS in Papua has decreased over the past ~30
      35 years, it remains higher than the global average. There was a high prevalence
      of overlapping ALS, parkinsonism and CI, which has also been previously reported
      in Guam and Kii.

PMID- 24740978
TI  - The barriers to and enablers of providing reasonably adjusted health services to
      people with intellectual disabilities in acute hospitals: evidence from a mixed
      methods study.
AB  - OBJECTIVE: To identify the factors that promote and compromise the implementation
      of reasonably adjusted healthcare services for patients with intellectual
      disabilities in acute National Health Service (NHS) hospitals. DESIGN: A mixed
      methods study involving interviews, questionnaires and participant observation
      (July 2011-March 2013). SETTING: Six acute NHS hospital trusts in England.
      METHODS: Reasonable adjustments for people with intellectual disabilities were
      identified through the literature. Data were collected on implementation and
      staff understanding of these adjustments. RESULTS: Data collected included staff
      questionnaires (n=990), staff interviews (n=68), interviews with adults with
      intellectual disabilities (n=33), questionnaires (n=88) and interviews (n=37)
      with carers of patients with intellectual disabilities, and expert panel
      discussions (n=42). Hospital strategies that supported implementation of
      reasonable adjustments did not reliably translate into consistent provision of
      such adjustments. Good practice often depended on the knowledge, understanding
      and flexibility of individual staff and teams, leading to the delivery of
      reasonable adjustments being haphazard throughout the organisation. Major
      barriers included: lack of effective systems for identifying and flagging
      patients with intellectual disabilities, lack of staff understanding of the
      reasonable adjustments that may be needed, lack of clear lines of responsibility
      and accountability for implementing reasonable adjustments, and lack of
      allocation of additional funding and resources. Key enablers were the
      Intellectual Disability Liaison Nurse and the ward manager. CONCLUSIONS: The
      evidence suggests that ward culture, staff attitudes and staff knowledge are
      crucial in ensuring that hospital services are accessible to vulnerable patients.
      The authors suggest that flagging the need for specific reasonable adjustments,
      rather than the vulnerable condition itself, may address some of the barriers.
      Further research is recommended that describes and quantifies the most frequently
      needed reasonable adjustments within the hospital pathways of vulnerable patient
      groups, and the most effective organisational infrastructure required to
      guarantee their use, together with resource implications.

PMID- 24740980
TI  - Why is health care inflation greater than general inflation?

PMID- 24740979
TI  - Positive health effects of the natural outdoor environment in typical populations
      in different regions in Europe (PHENOTYPE): a study programme protocol.
AB  - INTRODUCTION: Growing evidence suggests that close contact with nature brings
      benefits to human health and well-being, but the proposed mechanisms are still
      not well understood and the associations with health remain uncertain. The
      Positive Health Effects of the Natural Outdoor environment in Typical Populations
      in different regions in Europe (PHENOTYPE) project investigates the
      interconnections between natural outdoor environments and better human health and
      well-being. AIMS AND METHODS: The PHENOTYPE project explores the proposed
      underlying mechanisms at work (stress reduction/restorative function, physical
      activity, social interaction, exposure to environmental hazards) and examines the
      associations with health outcomes for different population groups. It implements
      conventional and new innovative high-tech methods to characterise the natural
      environment in terms of quality and quantity. Preventive as well as therapeutic
      effects of contact with the natural environment are being covered. PHENOTYPE
      further addresses implications for land-use planning and green space management.
      The main innovative part of the study is the evaluation of possible short-term
      and long-term associations of green space and health and the possible underlying
      mechanisms in four different countries (each with quite a different type of green
      space and a different use), using the same methodology, in one research
      programme. This type of holistic approach has not been undertaken before.
      Furthermore there are technological innovations such as the use of remote sensing
      and smartphones in the assessment of green space. CONCLUSIONS: The project will
      produce a more robust evidence base on links between exposure to natural outdoor
      environment and human health and well-being, in addition to a better integration
      of human health needs into land-use planning and green space management in rural
      as well as urban areas.

PMID- 24740981
TI  - Current evidence of anti-tumor necrosis factor alpha treatment efficacy in
      childhood chronic uveitis: a systematic review and meta-analysis approach of
      individual drugs.
AB  - OBJECTIVE: To summarize evidence regarding the effectiveness of anti-tumor
      necrosis factor alpha (anti-TNFalpha) treatments in childhood autoimmune chronic
      uveitis (ACU), refractory to previous disease-modifying antirheumatic drugs
      (DMARDs). METHODS: A systematic search between January 2000 and October 2012 was
      conducted using EMBase, Ovid Medline, Evidence-Based Medicine (EBM) Reviews:
      American College of Physicians Journal Club, Cochrane libraries, and EBM Reviews.
      Studies investigating the efficacy of anti-TNFalpha therapy, in children ages
      <=16 years, as the first treatment with a biologic agent for ACU, refractory to
      topical and/or systemic steroid therapy and at least 1 DMARD, were eligible for
      inclusion. The primary outcome measure was the improvement of intraocular
      inflammation, as defined by the Standardization of Uveitis Nomenclature Working
      Group criteria. We determined a combined estimate of the proportion of children
      responding to anti-TNFalpha treatment, including etanercept (ETA), infliximab
      (INF), or adalimumab (ADA). RESULTS: We initially identified 989 articles, of
      which 148 were potentially eligible. In total, 22 retrospective chart reviews and
      1 randomized clinical trial were deemed eligible, thus including 229 children
      (ADA: n = 31, ETA: n = 54, and INF: n = 144). On pooled analysis of observational
      studies, the proportion of responding children was 87% (95% confidence interval
      [95% CI] 75-98%) for ADA, 72% (95% CI 64-79%) for INF, and 33% (95% CI 19-47%)
      for ETA. There was no difference in the proportion of responders between ADA and
      INF (chi(2) = 3.06, P = 0.08), although both showed superior efficacy compared
      with ETA (ADA versus ETA: chi(2) = 20.9, P < 0.001 and INF versus ETA: chi(2) =
      20.9, P < 0.001). CONCLUSION: Although randomized controlled trials are needed,
      the available evidence suggests that INF and ADA provide proven similar benefits
      in the treatment of childhood ACU, and they are both superior to ETA.

PMID- 24740982
TI  - Intranasal Drainage for Pediatric Nasal Abscesses.
AB  - Nasal abscesses of the tip or soft tissues are uncommon in children. We describe
      an endonasal surgical approach for nasal abscesses based on our experience with 3
      children at our tertiary care, academic children's hospital. All presented with
      significant nasal pain out of proportion to the physical examination findings,
      along with edema, induration, and some intermittent bleeding and discharge of
      sebaceous and/or keratinous debris. Parenteral antibiotics were administered for
      an initial period of at least 24 hours in all cases, without any significant
      improvement in the patients' symptoms. Computed tomography (CT) with intravenous
      contrast was diagnostic in all cases. Symptomatic relief was achieved immediately
      postoperatively. No child required a second drainage procedure, and all children
      had an uneventful recovery.

PMID- 24740983
TI  - Analysis of Nasal Septal Deviation in Cleft Palate and/or Alveolus Patients Using
      Cone-Beam Computed Tomography.
AB  - OBJECTIVE: This study was performed to analyze features of nasal septal deviation
      of patients with different cleft types and noncleft controls. STUDY DESIGN: Case
      control study. SETTING: West China Hospital of Stomatology, Chengdu, China.
      SUBJECTS AND METHODS: Sixty-six patients with palatal and/or alveolar cleft and
      42 noncleft controls were recruited in the study. All the subjects have undergone
      cone-beam computed tomography scan. The range, angle, vertical location, and
      convex direction of nasal septal deviation were carefully studied for each
      subject. The data were compared between the cleft group and noncleft controls.
      The differences of deviation among various cleft types were also carefully
      evaluated to demonstrate whether the differences in cleft types affect the
      features of nasal septal deviation. RESULTS: The mean range 7.71 mm and angle
      10.37 degrees  of nasal septal deviation in cleft group were significantly
      greater than that in control group of 1.96 mm and 2.34 degrees . The maximum
      point of nasal septal deviation in cleft group vertically occurred more often at
      inferior turbinate level (27/66) followed by lower inter-turbinate level (16/66)
      and middle turbinate level (11/66). Patients with complete cleft palate presented
      greater deviation than incomplete cleft palate or simple cleft alveolus patients.
      The convex direction of deviation was to the cleft side for all patients with
      complete cleft palate or simple alveolar cleft. CONCLUSION: Patients with cleft
      palate and/or alveolus presented greater deviation of nasal septum than noncleft
      controls. Patients of different cleft types showed various severity and features
      of nasal septal deviation.

PMID- 24740984
TI  - Tracking protein turnover and degradation by microscopy: photo-switchable versus
      time-encoded fluorescent proteins.
AB  - Expanded fluorescent protein techniques employing photo-switchable and
      fluorescent timer proteins have become important tools in biological research.
      These tools allow researchers to address a major challenge in cell and
      developmental biology, namely obtaining kinetic information about the processes
      that determine the distribution and abundance of proteins in cells and tissues.
      This knowledge is often essential for the comprehensive understanding of a
      biological process, and/or required to determine the precise point of
      interference following an experimental perturbation. 

PMID- 24740986
TI  - Occipital bending in depression.
AB  - There are reports of differences in occipital lobe asymmetry within psychiatric
      populations when compared with healthy control subjects. Anecdotal evidence and
      enlarged lateral ventricles suggests that there may also be a different pattern
      of curvature whereby one occipital lobe wraps around the other, termed 'occipital
      bending'. We investigated the prevalence of occipital bending in 51 patients with
      major depressive disorder (males mean age = 41.96 +/- 14.00 years, females mean
      age = 40.71 +/- 12.41 years) and 48 age- and sex-matched healthy control subjects
      (males mean age = 40.29 +/- 10.23 years, females mean age = 42.47 +/- 14.25
      years) and found the prevalence to be three times higher among patients with
      major depressive disorder (18/51, 35.3%) when compared with control subjects
      (6/48, 12.5%). The results suggest that occipital bending is more common among
      patients with major depressive disorder than healthy subjects, and that occipital
      asymmetry and occipital bending are separate phenomena. Incomplete neural pruning
      may lead to the cranial space available for brain growth being restricted, or
      ventricular enlargement may exacerbate the natural occipital curvature patterns,
      subsequently causing the brain to become squashed and forced to 'wrap' around the
      other occipital lobe. Although the clinical implications of these results are
      unclear, they provide an impetus for further research into the relevance of
      occipital bending in major depression disorder. 

PMID- 24740985
TI  - Polar delivery in plants; commonalities and differences to animal epithelial
      cells.
AB  - Although plant and animal cells use a similar core mechanism to deliver proteins
      to the plasma membrane, their different lifestyle, body organization and specific
      cell structures resulted in the acquisition of regulatory mechanisms that vary in
      the two kingdoms. In particular, cell polarity regulators do not seem to be
      conserved, because genes encoding key components are absent in plant genomes. In
      plants, the broad knowledge on polarity derives from the study of auxin
      transporters, the PIN-FORMED proteins, in the model plant Arabidopsis thaliana.
      In animals, much information is provided from the study of polarity in epithelial
      cells that exhibit basolateral and luminal apical polarities, separated by tight
      junctions. In this review, we summarize the similarities and differences of the
      polarization mechanisms between plants and animals and survey the main genetic
      approaches that have been used to characterize new genes involved in polarity
      establishment in plants, including the frequently used forward and reverse
      genetics screens as well as a novel chemical genetics approach that is expected
      to overcome the limitation of classical genetics methods. 

PMID- 24740987
TI  - Anatomical correlates of reward-seeking behaviours in behavioural variant
      frontotemporal dementia.
AB  - Behavioural variant frontotemporal dementia is characterized by abnormal
      responses to primary reward stimuli such as food, sex and intoxicants, suggesting
      abnormal functioning of brain circuitry mediating reward processing. The goal of
      this analysis was to determine whether abnormalities in reward-seeking behaviour
      in behavioural variant frontotemporal dementia are correlated with atrophy in
      regions known to mediate reward processing. Review of case histories in 103
      patients with behavioural variant frontotemporal dementia identified overeating
      or increased sweet food preference in 80 (78%), new or increased alcohol or drug
      use in 27 (26%), and hypersexuality in 17 (17%). For each patient, a primary
      reward-seeking score of 0-3 was created with 1 point given for each target
      behaviour (increased seeking of food, drugs, or sex). Voxel-based morphometry
      performed in 91 patients with available imaging revealed that right ventral
      putamen and pallidum atrophy correlated with higher reward-seeking scores. Each
      of the reward-related behaviours involved partially overlapping right hemisphere
      reward circuit regions including putamen, globus pallidus, insula and thalamus.
      These findings indicate that in some patients with behavioural variant
      frontotemporal dementia, low volume of subcortical reward-related structures is
      associated with increased pursuit of primary rewards, which may be a product of
      increased thalamocortical feedback. 

PMID- 24740988
TI  - Functional deficits in carpal tunnel syndrome reflect reorganization of primary
      somatosensory cortex.
AB  - Carpal tunnel syndrome, a median nerve entrapment neuropathy, is characterized by
      sensorimotor deficits. Recent reports have shown that this syndrome is also
      characterized by functional and structural neuroplasticity in the primary
      somatosensory cortex of the brain. However, the linkage between this
      neuroplasticity and the functional deficits in carpal tunnel syndrome is unknown.
      Sixty-three subjects with carpal tunnel syndrome aged 20-60 years and 28 age- and
      sex-matched healthy control subjects were evaluated with event-related functional
      magnetic resonance imaging at 3 T while vibrotactile stimulation was delivered to
      median nerve innervated (second and third) and ulnar nerve innervated (fifth)
      digits. For each subject, the interdigit cortical separation distance for each
      digit's contralateral primary somatosensory cortex representation was assessed.
      We also evaluated fine motor skill performance using a previously validated
      psychomotor performance test (maximum voluntary contraction and visuomotor
      pinch/release testing) and tactile discrimination capacity using a four-finger
      forced choice response test. These biobehavioural and clinical metrics were
      evaluated and correlated with the second/third interdigit cortical separation
      distance. Compared with healthy control subjects, subjects with carpal tunnel
      syndrome demonstrated reduced second/third interdigit cortical separation
      distance (P < 0.05) in contralateral primary somatosensory cortex, corroborating
      our previous preliminary multi-modal neuroimaging findings. For psychomotor
      performance testing, subjects with carpal tunnel syndrome demonstrated reduced
      maximum voluntary contraction pinch strength (P < 0.01) and a reduced number of
      pinch/release cycles per second (P < 0.05). Additionally, for four-finger forced
      choice testing, subjects with carpal tunnel syndrome demonstrated greater
      response time (P < 0.05), and reduced sensory discrimination accuracy (P < 0.001)
      for median nerve, but not ulnar nerve, innervated digits. Moreover, the
      second/third interdigit cortical separation distance was negatively correlated
      with paraesthesia severity (r = -0.31, P < 0.05), and number of pinch/release
      cycles (r = -0.31, P < 0.05), and positively correlated with the second and third
      digit sensory discrimination accuracy (r = 0.50, P < 0.05). Therefore, reduced
      second/third interdigit cortical separation distance in contralateral primary
      somatosensory cortex was associated with worse symptomatology (particularly
      paraesthesia), reduced fine motor skill performance, and worse sensory
      discrimination accuracy for median nerve innervated digits. In conclusion,
      primary somatosensory cortex neuroplasticity for median nerve innervated digits
      in carpal tunnel syndrome is indeed maladaptive and underlies the functional
      deficits seen in these patients. 

PMID- 24740989
TI  - Hypothalamic sidedness in mitochondrial metabolism: new perspectives.
AB  - Morphofunctional changes in hypothalamic neurons are highly energy dependent and
      rely on mitochondrial metabolism. Therefore, mitochondrial adenosine triphosphate
      production plays a permissive role in hypothalamic regulatory events. Here, we
      demonstrated that in the female rat hypothalamus, mitochondrial metabolism and
      tissue oxygenation show an asymmetric lateralization during the estrous cycle.
      This asymmetry was not detected in males. The observed sidedness suggests that
      estrous cycle-linked hypothalamic functions in females are based on hemispheric
      distinction. The novel concept of hypothalamic asymmetry necessitates the
      revision of hypothalamic neural circuits, synaptic reorganization, and the role
      of hypothalamic sides in the regulation of integrated homeostatic functions. 

PMID- 24740990
TI  - Effect of postnatal maternal protein intake on prenatal programming of
      hypertension.
AB  - This study examined whether postnatal maternal dietary protein deprivation during
      the time of nursing can program hypertension when the offspring are studied as
      adults. Rats were fed either a 6% or 20% protein diet during the second half of
      pregnancy and continued on the same diet while rats were nursing their pups. The
      neonates of all of the rats were cross-fostered to a different mother and studied
      as adults. Adult rats that had a normal prenatal environment but were reared by
      mothers fed a low-protein diet until weaning (20%-6%) were hypertensive, had a
      higher renal Na(+)-K(+)-2Cl(-) cotransporter (NKCC2) and Na(+)-Cl(-)
      cotransporter (NCC) protein abundance yet a comparable number of glomeruli, and
      had higher plasma renin and angiotensin II levels compared to control (20%-20%).
      Rats whose mothers were fed a 6% protein diet and cross-fostered to a different
      rat fed a 6% protein diet until weaning (6%-6%) were hypertensive, had elevated
      plasma renin and angiotensin II levels, and had a reduction in nephron number but
      had NKCC2 and NCC levels comparable to 20% to 20% offspring. The 6% to 20% had
      blood pressure and glomerular numbers comparable to 20% to 20% rats. The
      hypertension resulting from prenatal dietary protein deprivation can be
      normalized by improving the postnatal environment. Combined prenatal and
      postnatal maternal dietary protein deprivation and maternal dietary protein
      deprivation while nursing alone (20%-6%) results in hypertension, but the
      mechanism for the hypertension in these groups is different. 

PMID- 24740991
TI  - Asphyxia and therapeutic hypothermia modulate plasma nitrite concentrations and
      carotid vascular resistance in preterm fetal sheep.
AB  - In this study, we tested the hypothesis that cerebral hypoperfusion after
      asphyxia and induced hypothermia is associated with reduced circulating nitrite
      levels as an index of nitric oxide synthase (NOS) activity. The preterm fetal
      sheep at 0.7 gestation (103-104 days, term = 147 days) received 25-minute
      umbilical cord occlusion, followed by mild whole-body cooling from 30 minutes to
      72 hours after occlusion. Occlusion and induced hypothermia were independently
      associated with reduced carotid vascular conductance (CaVC) from 2 to 72 hours,
      and with transiently suppressed plasma nitrite levels at 6 hours. There was a
      significant within-subjects correlation (r(2) = 0.33, P = .002) between CaVC and
      plasma nitrite values in the first 24 hours after occlusion but not after sham
      occlusion. These findings suggest that in preterm fetal sheep, changes in NOS
      activity are an important mediator of changes in carotid vascular tone in the
      early recovery phase after asphyxia and may help mediate some of the vascular
      effects of induced hypothermia.

PMID- 24740992
TI  - Comparison of continuous non-invasive finger arterial pressure monitoring with
      conventional intermittent automated arm arterial pressure measurement in patients
      under general anaesthesia.
AB  - BACKGROUND: For a majority of patients undergoing anaesthesia for general
      surgery, mean arterial pressure (MAP) is only measured intermittently by arm cuff
      oscillometry (MAPiNIAP). In contrast, the Nexfin((r)) device provides continuous
      non-invasive measurement of MAP (MAPcNIAP) using a finger cuff. We explored the
      agreement of MAPcNIAP and MAPiNIAP with the gold standard: continuous invasive
      MAP measurement by placement of a radial artery catheter (MAPinvasive). METHODS:
      In a total of 120 patients undergoing elective general surgery and clinically
      requiring MAPinvasive measurement, MAPiNIAP and MAPcNIAP were measured in a 30
      min time period at an arbitrary moment during surgery with stable haemodynamics.
      MAPiNIAP was measured every 5 min. RESULTS: Data from 112 patients were analysed.
      Compared with MAPinvasive, modified Bland-Altman analysis revealed a bias (sd) of
      2 (9) mm Hg for MAPcNIAP and -2 (12) mm Hg for MAPiNIAP. Percentage errors for
      MAPcNIAP and MAPiNIAP were 22% and 32%, respectively. CONCLUSIONS: In a
      haemodynamically stable phase in patients undergoing general anaesthesia, the
      agreement with invasive MAP of continuous non-invasive measurement using a finger
      cuff was not inferior to the agreement of intermittent arm cuff oscillometry.
      Continuous measurements using a finger cuff can interchangeably be used as an
      alternative for intermittent arm cuff oscillometry in haemodynamically stable
      patients, with the advantage of beat-to-beat haemodynamic monitoring. CLINICAL
      TRIAL REGISTRATION: NCT 01362335 (clinicaltrials.gov).

PMID- 24740993
TI  - Response to "Aortic Coarctation Complicated by Aortoesophageal Fistula: Fortune
      Is Blind!".

PMID- 24740994
TI  - Aortic Coarctation Complicated by Aortoesophageal Fistula: Fortune Is Blind!

PMID- 24740995
TI  - Obligate progression precedes lung adenocarcinoma dissemination.
AB  - Despite its clinical importance, very little is known about the natural history
      and molecular underpinnings of lung cancer dissemination and metastasis. Here, we
      used a genetically engineered mouse model of metastatic lung adenocarcinoma in
      which cancer cells are fluorescently marked to determine whether dissemination is
      an inherent ability or a major acquired phenotype during lung adenocarcinoma
      metastasis. We find very little evidence for dissemination from oncogenic KRAS
      driven hyperplasias or most adenocarcinomas. p53 loss is insufficient to drive
      dissemination but rather enables rare cancer cells in a small fraction of primary
      adenocarcinomas to gain alterations that drive dissemination. Molecular
      characterization of disseminated tumor cells indicates that downregulation of the
      transcription factor Nkx2-1 precedes dissemination. Finally, we show that
      metastatic primary tumors possess a highly proliferative subpopulation of cells
      with characteristics matching those of disseminating cells. We propose that
      dissemination is a major hurdle during the natural course of lung adenocarcinoma
      metastasis. SIGNIFICANCE: Because of its aggressively metastatic nature, lung
      cancer is the top cancer killer of both men and women in the United States. We
      show that, unlike in other cancer types, lung cancer dissemination is a major
      initial barrier to metastasis. Our findings provide insight into the effect of
      p53 deficiency and downregulation of Nkx2-1 during lung adenocarcinoma
      progression.

PMID- 24740996
TI  - Haploinsufficiency of an RB-E2F1-Condensin II complex leads to aberrant
      replication and aneuploidy.
AB  - Genome instability is a characteristic of malignant cells; however, evidence for
      its contribution to tumorigenesis has been enigmatic. In this study, we
      demonstrate that the retinoblastoma protein, E2F1, and Condensin II localize to
      discrete genomic locations including major satellite repeats at pericentromeres.
      In the absence of this complex, aberrant replication ensues followed by defective
      chromosome segregation in mitosis. Surprisingly, loss of even one copy of the
      retinoblastoma gene reduced recruitment of Condensin II to pericentromeres and
      caused this phenotype. Using cancer genome data and gene-targeted mice, we
      demonstrate that mutation of one copy of RB1 is associated with chromosome copy
      number variation in cancer. Our study connects DNA replication and chromosome
      structure defects with aneuploidy through a dosage-sensitive complex at
      pericentromeric repeats. SIGNIFICANCE: Genome instability is inherent to most
      cancers and is the basis for selective killing of cancer cells by genotoxic
      therapeutics. In this report, we demonstrate that instability can be caused by
      loss of a single allele of the retinoblastoma gene that prevents proper
      replication and condensation of pericentromeric chromosomal regions, leading to
      elevated levels of aneuploidy in cancer.

PMID- 24740998
TI  - Multivariate tests based on interpoint distances with application to magnetic
      resonance imaging.
AB  - The multivariate location problem is addressed. The most familiar method to
      address the problem is the Hotelling test. When the hypothesis of normal
      distributions holds, the Hotelling test is optimal. Unfortunately, in practice
      the distributions underlying the samples are generally unknown and without
      assuming normality the finite sample unbiasedness of the Hotelling test is not
      guaranteed. Moreover, high-dimensional data are increasingly encountered when
      analyzing medical and biological problems, and in these situations the Hotelling
      test performs poorly or cannot be computed. A test that is unbiased for non
      normal data, for small sample sizes as well as for two-sided alternatives and
      that can be computed for high-dimensional data has been recently proposed and is
      based on the ranks of the interpoint Euclidean distances between observations.
      Five modifications of this test are proposed and compared to the original test
      and the Hotelling test. Unbiasedness and consistency of the tests are proven and
      the problem of power computation is addressed. It is shown that two of the
      modified interpoint distance-based tests are always more powerful than the
      original test. Particularly, the modified test based on the Tippett criterium is
      suggested when the assumption of normality is not tenable and/or in case of high
      dimensional data with complex dependence structure which are typical in molecular
      biology and medical imaging. A practical application to a case-control study
      where functional magnetic resonance imaging is used is discussed.

PMID- 24740997
TI  - A high-throughput fluorimetric assay for 2-hydroxyglutarate identifies Zaprinast
      as a glutaminase inhibitor.
AB  - Recently identified isocitrate dehydrogenase (IDH) mutations lead to the
      production of 2-hydroxyglutarate (2HG), an oncometabolite aberrantly elevated in
      selected cancers. We developed a facile and inexpensive fluorimetric microplate
      assay for the quantitation of 2HG and performed an unbiased small-molecule screen
      in live cells to identify compounds capable of perturbing 2HG production.
      Zaprinast, a phosphodiesterase 5 inhibitor, was identified as an efficacious
      modulator of 2HG production and confirmed to lower 2HG levels in vivo. The
      mechanism of action was not due to cGMP stabilization, but rather, profiling of
      metabolites upstream of mutant IDH1 pointed to targeted inhibition of the enzyme
      glutaminase (GLS). Zaprinast treatment reversed histone hypermethylation and soft
      agar growth of IDH1-mutant cells, and treatment of glutamine-addicted pancreatic
      cancer cells reduced growth and sensitized cells to oxidative damage. Thus,
      Zaprinast is efficacious against glutamine metabolism and further establishes the
      therapeutic linkages between GLS and 2HG-mediated oncogenesis. SIGNIFICANCE: Gain
      of-function IDH mutations are common events in glioma, acute myelogenous
      leukemia, and other cancer types, which lead to the accumulation of the
      oncometabolite 2HG. We show that the drug Zaprinast is capable of reducing
      cellular 2HG levels by inhibiting the upstream enzyme GLS, thus identifying a new
      strategy to target 2HG production in selected IDH-mutant cancers.

PMID- 24740999
TI  - Assessing the inter-rater agreement for ordinal data through weighted indexes.
AB  - Assessing the inter-rater agreement between observers, in the case of ordinal
      variables, is an important issue in both the statistical theory and biomedical
      applications. Typically, this problem has been dealt with the use of Cohen's
      weighted kappa, which is a modification of the original kappa statistic, proposed
      for nominal variables in the case of two observers. Fleiss (1971) put forth a
      generalization of kappa in the case of multiple observers, but both Cohen's and
      Fleiss' kappa could have a paradoxical behavior, which may lead to a difficult
      interpretation of their magnitude. In this paper, a modification of Fleiss'
      kappa, not affected by paradoxes, is proposed, and subsequently generalized to
      the case of ordinal variables. Monte Carlo simulations are used both to testing
      statistical hypotheses and to calculating percentile and bootstrap-t confidence
      intervals based on this statistic. The normal asymptotic distribution of the
      proposed statistic is demonstrated. Our results are applied to the classical
      Holmquist et al.'s (1967) dataset on the classification, by multiple observers,
      of carcinoma in situ of the uterine cervix. Finally, we generalize the use of s*
      to a bivariate case.

PMID- 24741000
TI  - Bayesian latent structure modeling of walking behavior in a physical activity
      intervention.
AB  - The analysis of walking behavior in a physical activity intervention is
      considered. A Bayesian latent structure modeling approach is proposed whereby the
      ability and willingness of participants is modeled via latent effects. The
      dropout process is jointly modeled via a linked survival model. Computational
      issues are addressed via posterior sampling and a simulated evaluation of the
      longitudinal model's ability to recover latent structure and predictor effects is
      considered. We evaluate the effect of a variety of socio-psychological and
      spatial neighborhood predictors on the propensity to walk and the estimation of
      latent ability and willingness in the full study.

PMID- 24741001
TI  - Mobile apps: are we culturally out of signal?

PMID- 24741002
TI  - How do clinicians with different training backgrounds manage walk-in patients in
      the ED setting?
AB  - OBJECTIVE: To compare the initial assessment and management of walk-in emergency
      department (ED) patients between different types of healthcare providers.
      SETTING: A large teaching hospital with an annual ED census of 140 000 adult
      patients. METHODS: A random sample of 384 patients who self-presented to the ED
      was obtained. A detailed analysis of each patient record was performed by two
      clinicians. Data were obtained on the presenting condition, and disposition of
      each patient, either into the ED for further assessment, or discharge. RESULTS:
      GPs were significantly more likely to discharge patients home as compared to
      emergency nurses. ED senior nurses were more likely than GPs to stream patients
      into the ED for further assessment. Of the patients referred into the ED for
      further assessment by senior ED nurses, the majority were discharged home. There
      were insufficient numbers of emergency physician assessments for meaningful
      statistical analysis. CONCLUSIONS: The clinician groups studied here demonstrated
      different patterns of discharge and referral, reflecting their training and
      experience. When planning operational procedures, the training and background of
      the staff allocated to each area should be considered.

PMID- 24741003
TI  - Hypoxia, haemorrhage and hypotension: the interface between emergency medicine
      and intensive care medicine.
AB  - This subjective review is based on a presentation made at the College of
      Emergency Medicine Scientific Conference in September 2013. My theme was that
      there are certain features of the critically ill which cause understandable
      anxiety, namely hypoxia, haemorrhage and hypotension. So, I have selected papers
      relevant to the management of these frightening situations. 

PMID- 24741004
TI  - A new horizon in the treatment of biofilm-associated tonsillitis.
AB  - OBJECTIVE: To demonstrate the efficacy of tonsil brushing in patients with
      chronic tonsillitis to remove the microbial biofilm on the tonsil surface using
      an in vitro model. DESIGN: Specimens from patients undergoing tonsillectomy were
      evaluated prior to and following surface cleaning methods, including rinsing and
      brushing, using scanning electron microscopy (SEM). PATIENTS: The study
      population consisted of 25 randomly selected patients with chronic tonsillitis.
      INTERVENTIONS: Specimens were collected and divided into four portions. Each
      portion received distinct surface cleaning methods and was immediately fixed for
      SEM examination. OUTCOME MEASURES: The biofilm layer on the surface of the
      tonsils was examined using SEM. The density of the biofilm layer and the degree
      of persistence of the biofilm after rinsing and brushing were measured. RESULTS:
      The surface biofilm of the tonsils in the first group, which were neither brushed
      nor rinsed, revealed a thick layer of biofilm on the mucosal surface. The second
      group of tonsils, which were only rinsed, also showed a thick layer of biofilm.
      The third group of tonsils, which were rinsed following gentle brushing using a
      soft toothbrush, showed a reduction in the thickness of the biofilm layer. The
      fourth group of tonsils, which were brushed with a hard brush, was almost devoid
      of a biofilm layer. CONCLUSION: Our results demonstrate that rinsing does not
      effectively remove the biofilm layer on the tonsil surface. The use of a harder
      brush was identified as a more powerful means of removing biofilm compared with a
      soft brush.

PMID- 24741005
TI  - Novel polymeric nanoparticles for intracellular delivery of peptide Cargos:
      antitumor efficacy of the BCL-2 conversion peptide NuBCP-9.
AB  - The preclinical development of peptidyl drugs for cancer treatment is hampered by
      their poor pharmacologic properties and cell penetrative capabilities in vivo. In
      this study, we report a nanoparticle-based formulation that overcomes these
      limitations, illustrating their utility in studies of the anticancer peptide
      NuBCP-9, which converts BCL-2 from a cell protector to a cell killer. NuBCP-9 was
      encapsulated in polymeric nanoparticles composed of a polyethylene glycol (PEG)
      modified polylactic acid (PLA) diblock copolymer (NuBCP-9/PLA-PEG) or PEG
      polypropylene glycol-PEG-modified PLA-tetrablock copolymer (NuBCP-9/PLA-PEG-PPG
      PEG). We found that peptide encapsulation was enhanced by increasing the PEG
      chain length in the block copolymers. NuBCP-9 release from the nanoparticles was
      controlled by both PEG chain length and the PLA molecular weight, permitting time
      release over sustained periods. Treatment of human cancer cells with these
      nanoparticles in vitro triggered apoptosis by NuBCP-9-mediated mechanism, with a
      potency similar to NuBCP-9 linked to a cell-penetrating poly-Arg peptide.
      Strikingly, in vivo administration of NuBCP-9/nanoparticles triggered complete
      regressions in the Ehrlich syngeneic mouse model of solid tumor. Our results
      illustrate an effective method for sustained delivery of anticancer peptides,
      highlighting the superior qualities of the novel PLA-PEG-PPG-PEG tetrablock
      copolymer formulation as a tool to target intracellular proteins.

PMID- 24741006
TI  - E2F1 responds to ultraviolet radiation by directly stimulating DNA repair and
      suppressing carcinogenesis.
AB  - In response to DNA damage, the E2F1 transcription factor is phosphorylated at
      serine 31 (serine 29 in mouse) by the ATM or ATR kinases, which promotes E2F1
      protein stabilization. Phosphorylation of E2F1 also leads to the recruitment of
      E2F1 to sites of DNA damage, where it functions to enhance DNA repair. To study
      the role of this E2F1 phosphorylation event in vivo, a knock-in mouse model was
      generated, in which serine 29 was mutated to alanine. The S29A mutation impairs
      E2F1 stabilization in response to ultraviolet (UV) radiation and doxorubicin
      treatment, but has little effect on the expression of E2F target genes. The
      apoptotic and proliferative responses to acute UV radiation exposure are also
      similar between wild-type and E2f1(S29A/) (S29A) mice. As expected, the S29A
      mutation prevents E2F1 association with damaged DNA and reduces DNA repair
      efficiency. Moreover, E2f1(S29A/) (S29A) mice display increased sensitivity to UV
      induced skin carcinogenesis. This knock-in mouse model thus links the ability of
      E2F1 to directly promote DNA repair with the suppression of tumor development.

PMID- 24741007
TI  - Patterns of maximum body size evolution in Cenozoic land mammals: eco
      evolutionary processes and abiotic forcing.
AB  - There is accumulating evidence that macroevolutionary patterns of mammal
      evolution during the Cenozoic follow similar trajectories on different
      continents. This would suggest that such patterns are strongly determined by
      global abiotic factors, such as climate, or by basic eco-evolutionary processes
      such as filling of niches by specialization. The similarity of pattern would be
      expected to extend to the history of individual clades. Here, we investigate the
      temporal distribution of maximum size observed within individual orders globally
      and on separate continents. While the maximum size of individual orders of large
      land mammals show differences and comprise several families, the times at which
      orders reach their maximum size over time show strong congruence, peaking in the
      Middle Eocene, the Oligocene and the Plio-Pleistocene. The Eocene peak occurs
      when global temperature and land mammal diversity are high and is best explained
      as a result of niche expansion rather than abiotic forcing. Since the Eocene,
      there is a significant correlation between maximum size frequency and global
      temperature proxy. The Oligocene peak is not statistically significant and may in
      part be due to sampling issues. The peak in the Plio-Pleistocene occurs when
      global temperature and land mammal diversity are low, it is statistically the
      most robust one and it is best explained by global cooling. We conclude that the
      macroevolutionary patterns observed are a result of the interplay between eco
      evolutionary processes and abiotic forcing. 

PMID- 24741008
TI  - Entropy-driven motility of Sinorhizobium meliloti on a semi-solid surface.
AB  - Sinorhizobium meliloti growing on soft agar can exhibit an unusual surface
      spreading behaviour that differs from other bacterial surface motilities.
      Bacteria in the colony secrete an exopolysaccharide-rich mucoid fluid that
      expands outward on the surface, carrying within it a suspension of actively
      dividing cells. The moving slime disperses the cells in complex and dynamic
      patterns indicative of simultaneous bacterial growth, swimming and aggregation.
      We find that while flagellar swimming is required to maintain the cells in
      suspension, the spreading and the associated pattern formation are primarily
      driven by the secreted exopolysaccharide EPS II, which creates two entropy
      increasing effects: an osmotic flow of water from the agar to the mucoid fluid
      and a crowding or depletion attraction between the cells. Activation of these
      physical/chemical phenomena may be a useful function for the high molecular
      weight EPS II, a galactoglucan whose biosynthesis is tightly regulated by the
      ExpR/SinI/SinR quorum-sensing system: unlike bacterial colonies that spread via
      bacterium-generated, physical propulsive forces, S. meliloti under quorum
      conditions may use EPS II to activate purely entropic forces within its
      environment, so that it can disperse by passively 'surfing' on those forces. 

PMID- 24741009
TI  - Veterinary and human vaccine evaluation methods.
AB  - Despite the universal importance of vaccines, approaches to human and veterinary
      vaccine evaluation differ markedly. For human vaccines, vaccine efficacy is the
      proportion of vaccinated individuals protected by the vaccine against a defined
      outcome under ideal conditions, whereas for veterinary vaccines the term is used
      for a range of measures of vaccine protection. The evaluation of vaccine
      effectiveness, vaccine protection assessed under routine programme conditions, is
      largely limited to human vaccines. Challenge studies under controlled conditions
      and sero-conversion studies are widely used when evaluating veterinary vaccines,
      whereas human vaccines are generally evaluated in terms of protection against
      natural challenge assessed in trials or post-marketing observational studies.
      Although challenge studies provide a standardized platform on which to compare
      different vaccines, they do not capture the variation that occurs under field
      conditions. Field studies of vaccine effectiveness are needed to assess the
      performance of a vaccination programme. However, if vaccination is performed
      without central co-ordination, as is often the case for veterinary vaccines,
      evaluation will be limited. This paper reviews approaches to veterinary vaccine
      evaluation in comparison to evaluation methods used for human vaccines. Foot-and
      mouth disease has been used to illustrate the veterinary approach.
      Recommendations are made for standardization of terminology and for rigorous
      evaluation of veterinary vaccines. 

PMID- 24741010
TI  - River density and landscape roughness are universal determinants of linguistic
      diversity.
AB  - Global linguistic diversity (LD) displays highly heterogeneous distribution
      patterns. Though the origin of the latter is not yet fully understood, remarkable
      parallelisms with biodiversity distribution suggest that environmental variables
      should play an essential role in their emergence. In an effort to construct a
      broad framework to explain world LD and to systematize the available data, we
      have investigated the significance of 14 variables: landscape roughness,
      altitude, river density, distance to lakes, seasonal maximum, average and minimum
      temperature, precipitation and vegetation, and population density. Landscape
      roughness and river density are the only two variables that universally affect
      LD. Overall, the considered set accounts for up to 80% of African LD, a figure
      that decreases for the joint Asia, Australia and the Pacific (69%), Europe (56%)
      and the Americas (53%). Differences among those regions can be traced down to a
      few variables that permit an interpretation of their current states of LD. Our
      processed datasets can be applied to the analysis of correlations in other
      similar heterogeneous patterns with a broad spatial distribution, the clearest
      example being biological diversity. The statistical method we have used can be
      understood as a tool for cross-comparison among geographical regions, including
      the prediction of spatial diversity in alternative scenarios or in changing
      environments. 

PMID- 24741011
TI  - Physical cognition: birds learn the structural efficacy of nest material.
AB  - It is generally assumed that birds' choice of structurally suitable materials for
      nest building is genetically predetermined. Here, we tested that assumption by
      investigating whether experience affected male zebra finches' (Taeniopygia
      guttata) choice of nest material. After a short period of building with
      relatively flexible string, birds preferred to build with stiffer string while
      those that had experienced a stiffer string were indifferent to string type.
      After building a complete nest with either string type, however, all birds
      increased their preference for stiff string. The stiffer string appeared to be
      the more effective building material as birds required fewer pieces of stiffer
      than flexible string to build a roofed nest. For birds that raised chicks
      successfully, there was no association between the material they used to build
      their nest and the type they subsequently preferred. Birds' material preference
      reflected neither the preference of their father nor of their siblings but
      juvenile experience of either string type increased their preference for stiffer
      string. Our results represent two important advances: (i) birds choose nest
      material based on the structural properties of the material; (ii) nest material
      preference is not entirely genetically predetermined as both the type and amount
      of experience influences birds' choices. 

PMID- 24741012
TI  - Drosophila adult and larval pheromones modulate larval food choice.
AB  - Insects use chemosensory cues to feed and mate. In Drosophila, the effect of
      pheromones has been extensively investigated in adults, but rarely in larvae. The
      colonization of natural food sources by Drosophila buzzatii and Drosophila
      simulans species may depend on species-specific chemical cues left in the food by
      larvae and adults. We identified such chemicals in both species and measured
      their influence on larval food preference and puparation behaviour. We also
      tested compounds that varied between these species: (i) two larval volatile
      compounds: hydroxy-3-butanone-2 and phenol (predominant in D. simulans and D.
      buzzatii, respectively), and (ii) adult cuticular hydrocarbons (CHs). Drosophila
      buzzatii larvae were rapidly attracted to non-CH adult conspecific cues, whereas
      D. simulans larvae were strongly repulsed by CHs of the two species and also by
      phenol. Larval cues from both species generally reduced larval attraction and
      pupariation on food, which was generally--but not always--low, and rarely
      reflected larval response. As these larval and adult pheromones specifically
      influence larval food search and the choice of a pupariation site, they may
      greatly affect the dispersion and survival of Drosophila species in nature.

PMID- 24741013
TI  - Individual recognition through olfactory-auditory matching in lemurs.
AB  - Individual recognition can be facilitated by creating representations of familiar
      individuals, whereby information from signals in multiple sensory modalities
      become linked. Many vertebrate species use auditory-visual matching to recognize
      familiar conspecifics and heterospecifics, but we currently do not know whether
      representations of familiar individuals incorporate information from other
      modalities. Ring-tailed lemurs (Lemur catta) are highly visual, but also
      communicate via scents and vocalizations. To investigate the role of olfactory
      signals in multisensory recognition, we tested whether lemurs can recognize
      familiar individuals through matching scents and vocalizations. We presented
      lemurs with female scents that were paired with the contact call either of the
      female whose scent was presented or of another familiar female from the same
      social group. When the scent and the vocalization came from the same individual
      versus from different individuals, females showed greater interest in the scents,
      and males showed greater interest in both the scents and the vocalizations,
      suggesting that lemurs can recognize familiar females via olfactory-auditory
      matching. Because identity signals in lemur scents and vocalizations are produced
      by different effectors and often encountered at different times (uncoupled in
      space and time), this matching suggests lemurs form multisensory representations
      through a newly recognized sensory integration underlying individual recognition.

PMID- 24741014
TI  - Chemically moderated gamete preferences predict offspring fitness in a broadcast
      spawning invertebrate.
AB  - Sperm chemoattraction, where sperm locate unfertilized eggs by following a
      concentration gradient of egg-derived chemoattractants, has been widely
      documented across numerous taxa. While marine invertebrates are favoured models
      for understanding the underlying mechanisms of sperm chemoattraction, the
      evolutionary forces underpinning the process remain enigmatic. Here, we show that
      in mussels (Mytilus galloprovincialis), chemically moderated gamete preferences
      promote assortative fertilizations between genetically compatible gametes. When
      offered the choice of egg clutches from two females, sperm exhibited consistent
      but differential 'preferences' for chemical cues secreted from conspecific eggs.
      Critically, our data reveal that the preferences shown by sperm during the egg
      choice trials are highly predictive of early embryonic viability when eggs and
      sperm from the same individuals are mixed during standard (no-choice)
      fertilization assays. Moreover, we demonstrate that by experimentally separating
      chemoattractants from eggs, sperm swimming behaviour is differentially regulated
      by egg-derived chemoattractants, and that these changes in sperm behaviour are
      highly consistent with observed patterns of gamete preferences, fertilization and
      larval survival. Together, this integrated series of experiments reveals that the
      behaviour of sperm is fine-tuned to respond differentially to the chemical
      signals emitted from different conspecific eggs, and that these choices have
      measurable fitness benefits. 

PMID- 24741015
TI  - Physiological regulation of evaporative water loss in endotherms: is the little
      red kaluta (Dasykaluta rosamondae) an exception or the rule?
AB  - It is a central paradigm of comparative physiology that the effect of humidity on
      evaporative water loss (EWL) is determined for most mammals and birds, in and
      below thermoneutrality, essentially by physics and is not under physiological
      regulation. Fick's law predicts that EWL should be inversely proportional to
      ambient relative humidity (RH) and linearly proportional to the water vapour
      pressure deficit (Deltawvp) between animal and air. However, we show here for a
      small dasyurid marsupial, the little kaluta (Dasykaluta rosamondae), that EWL is
      essentially independent of RH (and Deltawvp) at low RH (as are metabolic rate and
      thermal conductance). These results suggest regulation of a constant EWL
      independent of RH, a hitherto unappreciated capacity of endothermic vertebrates.
      Independence of EWL from RH conserves water and heat at low RH, and avoids
      physiological adjustments to changes in evaporative heat loss such as
      thermoregulation. Re-evaluation of previously published data for mammals and
      birds suggests that a lesser dependence of EWL on RH is observed more commonly
      than previously thought, suggesting that physiological independence of EWL of RH
      is not just an unusual capacity of a few species, such as the little kaluta, but
      a more general capability of many mammals and birds. 

PMID- 24741016
TI  - Investment in higher order central processing regions is not constrained by brain
      size in social insects.
AB  - The extent to which size constrains the evolution of brain organization and the
      genesis of complex behaviour is a central, unanswered question in evolutionary
      neuroscience. Advanced cognition has long been linked to the expansion of
      specific brain compartments, such as the neocortex in vertebrates and the
      mushroom bodies in insects. Scaling constraints that limit the size of these
      brain regions in small animals may therefore be particularly significant to
      behavioural evolution. Recent findings from studies of paper wasps suggest
      miniaturization constrains the size of central sensory processing brain centres
      (mushroom body calyces) in favour of peripheral, sensory input centres (antennal
      and optic lobes). We tested the generality of this hypothesis in diverse eusocial
      hymenopteran species (ants, bees and wasps) exhibiting striking variation in body
      size and thus brain size. Combining multiple neuroanatomical datasets from these
      three taxa, we found no universal size constraint on brain organization within or
      among species. In fact, small-bodied ants with miniscule brains had mushroom body
      calyces proportionally as large as or larger than those of wasps and bees with
      brains orders of magnitude larger. Our comparative analyses suggest that brain
      organization in ants is shaped more by natural selection imposed by visual
      demands than intrinsic design limitations. 

PMID- 24741017
TI  - How do animal territories form and change? Lessons from 20 years of mechanistic
      modelling.
AB  - Territory formation is ubiquitous throughout the animal kingdom. At the
      individual level, various behaviours attempt to exclude conspecifics from regions
      of space. At the population level, animals often segregate into distinct
      territorial areas. Consequently, it should be possible to derive territorial
      patterns from the underlying behavioural processes of animal movements and
      interactions. Such derivations are an important element in the development of an
      ecological theory that can predict the effects of changing conditions on
      territorial populations. Here, we review the approaches developed over the past
      20 years or so, which go under the umbrella of 'mechanistic territorial models'.
      We detail the two main strands to this research: partial differential equations
      and individual-based approaches, showing what each has offered to our
      understanding of territoriality and how they can be unified. We explain how they
      are related to other approaches to studying territories and home ranges, and
      point towards possible future directions. 

PMID- 24741018
TI  - Ecology and mode-of-life explain lifespan variation in birds and mammals.
AB  - Maximum lifespan in birds and mammals varies strongly with body mass such that
      large species tend to live longer than smaller species. However, many species
      live far longer than expected given their body mass. This may reflect
      interspecific variation in extrinsic mortality, as life-history theory predicts
      investment in long-term survival is under positive selection when extrinsic
      mortality is reduced. Here, we investigate how multiple ecological and mode-of
      life traits that should reduce extrinsic mortality (including volancy (flight
      capability), activity period, foraging environment and fossoriality),
      simultaneously influence lifespan across endotherms. Using novel phylogenetic
      comparative analyses and to our knowledge, the most species analysed to date (n =
      1368), we show that, over and above the effect of body mass, the most important
      factor enabling longer lifespan is the ability to fly. Within volant species,
      lifespan depended upon when (day, night, dusk or dawn), but not where (in the
      air, in trees or on the ground), species are active. However, the opposite was
      true for non-volant species, where lifespan correlated positively with both
      arboreality and fossoriality. Our results highlight that when studying the
      molecular basis behind cellular processes such as those underlying lifespan, it
      is important to consider the ecological selection pressures that shaped them over
      evolutionary time. 

PMID- 24741019
TI  - Three-dimensional space: locomotory style explains memory differences in rats and
      hummingbirds.
AB  - While most animals live in a three-dimensional world, they move through it to
      different extents depending on their mode of locomotion: terrestrial animals move
      vertically less than do swimming and flying animals. As nearly everything we know
      about how animals learn and remember locations in space comes from two
      dimensional experiments in the horizontal plane, here we determined whether the
      use of three-dimensional space by a terrestrial and a flying animal was
      correlated with memory for a rewarded location. In the cubic mazes in which we
      trained and tested rats and hummingbirds, rats moved more vertically than
      horizontally, whereas hummingbirds moved equally in the three dimensions.
      Consistent with their movement preferences, rats were more accurate in relocating
      the horizontal component of a rewarded location than they were in the vertical
      component. Hummingbirds, however, were more accurate in the vertical dimension
      than they were in the horizontal, a result that cannot be explained by their use
      of space. Either as a result of evolution or ontogeny, it appears that birds and
      rats prioritize horizontal versus vertical components differently when they
      remember three-dimensional space. 

PMID- 24741021
TI  - Mucosal lesions and mortality associated with the use of a ferric sulfate poultry
      litter amendment product.
AB  - Within hours of chick delivery, acute mortality and mucosal lesions were reported
      on 2 northeast Georgia broiler farms that had applied a ferric sulfate litter
      amendment product. Histological evaluation of the larynx, tongue, and surrounding
      stroma revealed multifocal areas of necrosis or degeneration of the oral mucosa,
      acute focal necrotizing cellulitis, and the presence of a brown-black pigmented
      material adhered to affected epithelial and mucosal surfaces. Multifocal to
      diffuse ventricular koilin degeneration and acute hemorrhage was also
      demonstrated in association with pigmented adherent material on affected
      surfaces. Perls iron stain revealed that adherent material on affected tissues
      was strongly positive for iron. An experiment was designed to reproduce clinical
      signs, lesions, and mortality using the same litter amendment product. The ferric
      sulfate litter amendment was confirmed as the causative agent.

PMID- 24741020
TI  - The oestrogen pathway underlies the evolution of exaggerated male cranial shapes
      in Anolis lizards.
AB  - Sexual dimorphisms vary widely among species. This variation must arise through
      sex-specific evolutionary modifications to developmental processes. Anolis
      lizards vary extensively in their expression of cranial dimorphism. Compared with
      other Anolis species, members of the carolinensis clade have evolved relatively
      high levels of cranial dimorphism; males of this clade have exceptionally long
      faces relative to conspecific females. Developmentally, this facial length
      dimorphism arises through an evolutionarily novel, clade-specific strategy. Our
      analyses herein reveal that sex-specific regulation of the oestrogen pathway
      underlies evolution of this exaggerated male phenotype, rather than the androgen
      or insulin growth factor pathways that have long been considered the primary
      regulators of male-biased dimorphism among vertebrates. Our results suggest
      greater intricacy in the genetic mechanisms that underlie sexual dimorphisms than
      previously appreciated. 

PMID- 24741022
TI  - Use of immunohistochemical staining and electron microscopy to aid in diagnosis
      of soft tissue sarcomas associated with the fetlock joint in two horses.
AB  - Soft tissue sarcomas of the equine distal limb associated with joints, sheaths,
      or bursae have rarely been reported. Accurate diagnosis of these tumors is
      challenging in both human beings and veterinary species. Immunohistochemical
      staining and transmission electron microscopy have been used in human beings to
      reduce misdiagnosis. The current report describes 2 mature horses presenting with
      lameness and swelling associated with the dorsal aspect of the
      metacarpo(tarso)phalangeal joint. In both cases, surgical excision was performed
      with subsequent histological analysis of the masses to determine the tissue of
      origin. In both cases, immunohistochemical staining and transmission electron
      microscopy aided the definitive diagnosis of fibrosarcoma associated with the
      fetlock joints of 2 horses.

PMID- 24741023
TI  - Retinal microvascular damage and vasogenic edema produced by Clostridium
      perfringens type D epsilon toxin in rats.
AB  - When the brain is exposed to large circulating levels of Clostridium perfringens
      type D epsilon toxin (EXT), microvascular damage with resulting severe,
      generalized, vasogenic edema seems to be principally responsible for the ensuing
      acute, and frequently fatal, neurologic disorder. However, although the blood
      retinal barrier resembles in many respects the blood-brain barrier, retinal
      changes in livestock with acute epsilon intoxication have not, to the authors'
      knowledge, been previously reported. In rats given an acute dose of ETX, retinal
      microvascular endothelial injury led to widespread vasogenic edema as assessed
      immunohistochemically by marked plasma albumin extravasation. As laboratory
      rodents are a good model of the domestic livestock disease produced by ETX, it is
      probable that the latter sustain some visual deficit when exposed to large doses
      of this potent neurotoxin.

PMID- 24741024
TI  - Chromogranin A predicts outcome in prostate cancer patients treated with
      abiraterone.
AB  - In this retrospective study, we evaluated the chromogranin A (CgA) baseline value
      as a predictor of clinical outcome in patients with metastatic castration
      resistant prostate cancer (CRPC) treated with abiraterone 1000 mg per day, whose
      disease progressed after docetaxel chemotherapy. In the 48 evaluable patients,
      serum CgA level was normal when <120  ng/ml (group A, n=16), within three times
      the upper normal value (UNV) when between 120 and 360 (group B, n=16), more than
      three times the UNV when >=360  ng/ml (group C, n=16). Decline in PSA level >=50%
      or more (PSA RR) was observed in 26 of 48 (54%) patients. PSA response rate did
      not correlate with the CgA groups. CgA levels more than three times the UNV
      predicted an early radiological progressive disease in eight of 11 cases (73%).
      The median progression-free survival (PFS) among the CgA groups A, B, and C was
      9.2, 9.2, and 4.8 months respectively, P=0.0459. The median overall survival (OS)
      among the CgA groups was 19.0, 18.8, and 10.8 months respectively, P=0.2092. In
      the multivariate analysis, PSA RR (nonresponsive vs responsive) and CgA levels
      (group 3 vs groups 1+2) were predictors of PFS (P=0.0002 and P=0.0047
      respectively), whereas PSA RR only was significantly associated with OS
      (P=0.0024), while CgA levels remained of borderline significance (P=0.0919). A
      serum CGA level more than three times the UNV predicted PFS and showed a trend vs
      OS prediction, independently from PSA response, in CRPC patients treated with
      abiraterone.

PMID- 24741025
TI  - Frequent EPAS1/HIF2alpha exons 9 and 12 mutations in non-familial
      pheochromocytoma.
AB  - Pheochromocytomas are neuroendocrine tumors arising from the adrenal medulla.
      While heritable mutations are frequently described, less is known about the
      genetics of sporadic pheochromocytoma. Mutations in genes involved in the
      cellular hypoxia response have been identified in tumors, and recently EPAS1,
      encoding HIF2alpha, has been revealed to be a new gene involved in the
      pathogenesis of pheochromocytoma and abdominal paraganglioma. The aim of this
      study was to further characterize EPAS1 alterations in non-familial
      pheochromocytomas. Tumor DNA from 42 adrenal pheochromocytoma cases with
      apparently sporadic presentation, without known hereditary mutations in
      predisposing genes, were analyzed for mutations in EPAS1 by sequencing of exons 9
      and 12, which contain the two hydroxylation sites involved in HIF2alpha
      degradation, and also exon 2. In addition, the copy number at the EPAS1 locus as
      well as transcriptome-wide gene expression were studied by DNA and RNA microarray
      analyses, respectively. We identified six missense EPAS1 mutations, three in exon
      9 and three in exon 12, in five of 42 pheochromocytomas (12%). The mutations were
      both somatic and constitutional, and had no overlap in 11 cases (26%) with
      somatic mutations in NF1 or RET. One sample had two different EPAS1 mutations,
      shown by cloning to occur in cis, possibly indicating a novel mechanism of
      HIF2alpha stabilization through inactivation of both hydroxylation sites. One of
      the tumors with an EPAS1 mutation also had a gain in DNA copy number at the EPAS1
      locus. All EPAS1-mutated tumors displayed a pseudo-hypoxic gene expression
      pattern, indicating an oncogenic role of the identified mutations. 

PMID- 24741026
TI  - Obesity and thyroid cancer.
AB  - Many studies have provided observational data on the association of obesity and
      thyroid cancers, but only few of them propose mechanisms that would permit a
      better understanding of the causal molecular mechanisms of this association.
      Considering that there is an increasing incidence of both obesity and thyroid
      cancers, we need to summarize and link recent studies in order to characterize
      and understand the contribution of obesity-related factors that might affect
      thyroid cancer development and progression. Adipose tissue is involved in many
      vital processes, including insulin sensitivity, angiogenesis, regulation of
      energy balance, activation of the complement system, and responses such as
      inflammation. Although these processes have their own molecular pathways, they
      involve the same molecules through which obesity and adipose tissue might exert
      their roles in carcinogenesis, not only affecting MAPK and PI3K or even insulin
      pathways, but also recruiting local inflammatory responses that could result in
      disease formation and progression. This review describes five important issues
      that might explain the link between excessive weight and thyroid cancer: thyroid
      hormones, insulin resistance, adipokines, inflammation, and sexual hormones.

PMID- 24741027
TI  - Activation of angiotensin-converting enzyme 2 improves cardiac electrical changes
      in ventricular repolarization in streptozotocin-induced hyperglycaemic rats.
AB  - AIMS: Diabetic patients present a high level of cardiac arrhythmias and risk of
      cardiac sudden death. The renin-angiotensin system (RAS) plays a key role in
      diabetes and cardiac diseases. The present study aimed to evaluate whether an
      angiotensin-converting enzyme 2 (ACE2) activator, diminazene aceturate (DIZE),
      could improve the streptozotocin (STZ)-induced electrical changes in ventricular
      repolarization in hyperglycaemic rats. METHODS AND RESULTS: Hyperglycaemia was
      induced in Wistar male rats with STZ (60 mg/kg/iv). After 4 weeks of STZ
      injection, rats were daily treated with saline (control) or DIZE (1 mg/kg/gavage)
      for four consecutive weeks. The cardiac electrical function was evaluated in vivo
      by electrocardiogram and in vitro by cardiac action potential records in
      different pacing frequencies. Treatment with DIZE was not able to reverse
      hyperglycaemia nor body weight loss. However, DIZE reversed hyperglycaemia
      induced cardiac electrical changes in ventricular repolarization. Specifically,
      animals treated with DIZE showed shorter QT and QTc intervals. In addition, ACE2
      activation was capable to shorten the cardiac action potential and also reverse
      the arrhythmic markers. Diminazene aceturate treatment did not induce arrhythmic
      events in normal, as well as in hyperglycaemic animals. CONCLUSION: Our data
      indicate that activation of ACE2 has a beneficial effect in hyperglycaemic rats,
      improving the cardiac electrical function. Thus, DIZE represents a promising new
      therapeutic agent to treat hyperglycaemia-induced cardiac electrical changes in
      ventricular repolarization.

PMID- 24741028
TI  - Thoracic aortic rupture and aortopulmonary fistulation in the Friesian horse:
      histomorphologic characterization.
AB  - Aortic rupture in horses is a rare condition. Although it is relatively common in
      the Friesian breed, only limited histopathologic information is available. Twenty
      Friesian horses (1-10 years old) were diagnosed with aortic rupture by postmortem
      examination. Ruptured aortic walls were analyzed with histology and
      immunohistochemistry. Based on the histologic and immunohistochemical findings,
      these cases were divided into 3 groups: acute (n = 4, 20%), subacute (n = 8,
      40%), and chronic (n = 8, 40%). Features common to samples from horses in all
      groups included accumulation of mucoid material; disorganization and
      fragmentation of the elastic laminae; aortic medial smooth muscle hypertrophy;
      and medial necrosis of varying degrees, ranging from mild and patchy in the acute
      cases to severe midzonal necrosis in the chronic cases. Inflammation, most likely
      secondary to medial necrosis, varied from predominantly neutrophilic infiltrates
      in the media and periadventitial tissue in the acute group to the presence of
      mainly hemosiderophages in the periadventitial tissue in the chronic group.
      Medial fibrosis with aberrant collagen morphology was seen in the subacute group
      and, more commonly, in the chronic group. Only minimal changes were seen in the
      aortic vasa vasorum. Smooth muscle hypertrophy and accumulation of mucoid
      material were not related to the age of the lesions. The findings of this study
      suggest that a connective tissue disorder affecting elastin or collagen in the
      aortic media is potentially the underlying cause of aortic rupture in Friesian
      horses. 

PMID- 24741029
TI  - Prognostic evaluation of feline mammary carcinomas: a review of the literature.
AB  - A large number of studies have investigated feline mammary tumors in an attempt
      to identify prognostic markers and generate comparative analyses with human
      breast cancer. Nevertheless, a retrospective base of assessments and the lack of
      standardization in methodology and study design have caused weakness in study
      results, making comparison difficult. We examined feline mammary tumor
      publications and evaluated postulated prognostic parameters according to the
      recently published "Recommended Guidelines for the Conduct and Evaluation of
      Prognostic Studies in Veterinary Oncology." Using these criteria, we determined
      with statistically significant reliability that prognostic parameters for feline
      mammary tumors are tumor grading and lymph node/lymphovascular invasion.
      Furthermore, tumor subtype, size, and staging are worthy of further standardized
      investigation. We present statistical significance for each studied parameter as
      well as its relevance to disease progression and survival. Our evaluation
      suggests that marker expression (ie, Ki67, HER2, ER) may provide relevant
      information applicable for therapeutic predictions; however, consensus efforts
      and protocol standardization are needed. We identify and discuss major points of
      concern--such as sample preservation and selection, standardization of
      immunohistochemical protocols, and evaluation of results--to provide support for
      subsequent reliable analyses.

PMID- 24741030
TI  - In sync: metaphor, mechanism or marker of mutual understanding?

PMID- 24741031
TI  - Seeing scenes: topographic visual hallucinations evoked by direct electrical
      stimulation of the parahippocampal place area.
AB  - In recent years, functional neuroimaging has disclosed a network of cortical
      areas in the basal temporal lobe that selectively respond to visual scenes,
      including the parahippocampal place area (PPA). Beyond the observation that
      lesions involving the PPA cause topographic disorientation, there is little
      causal evidence linking neural activity in that area to the perception of places.
      Here, we combined functional magnetic resonance imaging (fMRI) and intracranial
      EEG (iEEG) recordings to delineate place-selective cortex in a patient implanted
      with stereo-EEG electrodes for presurgical evaluation of drug-resistant epilepsy.
      Bipolar direct electrical stimulation of a cortical area in the collateral sulcus
      and medial fusiform gyrus, which was place-selective according to both fMRI and
      iEEG, induced a topographic visual hallucination: the patient described seeing
      indoor and outdoor scenes that included views of the neighborhood he lives in. By
      contrast, stimulating the more lateral aspect of the basal temporal lobe caused
      distortion of the patient's perception of faces, as recently reported (Parvizi et
      al., 2012). Our results support the causal role of the PPA in the perception of
      visual scenes, demonstrate that electrical stimulation of higher order visual
      areas can induce complex hallucinations, and also reaffirm direct electrical
      brain stimulation as a tool to assess the function of the human cerebral cortex. 

PMID- 24741033
TI  - Netrin and Frazzled regulate presynaptic gap junctions at a Drosophila giant
      synapse.
AB  - Netrin and its receptor, Frazzled, dictate the strength of synaptic connections
      in the giant fiber system (GFS) of Drosophila melanogaster by regulating gap
      junction localization in the presynaptic terminal. In Netrin mutant animals, the
      synaptic coupling between a giant interneuron and the "jump" motor neuron was
      weakened and dye coupling between these two neurons was severely compromised or
      absent. In cases in which Netrin mutants displayed apparently normal synaptic
      anatomy, half of the specimens exhibited physiologically defective synapses and
      dye coupling between the giant fiber (GF) and the motor neuron was reduced or
      eliminated, suggesting that gap junctions were disrupted in the Netrin mutants.
      When we examined the gap junctions with antibodies to Shaking-B (ShakB) Innexin,
      they were significantly decreased or absent in the presynaptic terminal of the
      mutant GF. Frazzled loss of function mutants exhibited similar defects in
      synaptic transmission, dye coupling, and gap junction localization. These data
      are the first to show that Netrin and Frazzled regulate the placement of gap
      junctions presynaptically at a synapse. 

PMID- 24741032
TI  - Environmental acoustic enrichment promotes recovery from developmentally degraded
      auditory cortical processing.
AB  - It has previously been shown that environmental enrichment can enhance structural
      plasticity in the brain and thereby improve cognitive and behavioral function. In
      this study, we reared developmentally noise-exposed rats in an acoustic-enriched
      environment for ~4 weeks to investigate whether or not enrichment could restore
      developmentally degraded behavioral and neuronal processing of sound frequency.
      We found that noise-exposed rats had significantly elevated sound frequency
      discrimination thresholds compared with age-matched naive rats. Environmental
      acoustic enrichment nearly restored to normal the behavioral deficit resulting
      from early disrupted acoustic inputs. Signs of both degraded frequency
      selectivity of neurons as measured by the bandwidth of frequency tuning curves
      and decreased long-term potentiation of field potentials recorded in the primary
      auditory cortex of these noise-exposed rats also were reversed partially. The
      observed behavioral and physiological effects induced by enrichment were
      accompanied by recovery of cortical expressions of certain NMDA and GABAA
      receptor subunits and brain-derived neurotrophic factor. These studies in a
      rodent model show that environmental acoustic enrichment promotes recovery from
      early noise-induced auditory cortical dysfunction and indicate a therapeutic
      potential of this noninvasive approach for normalizing neurological function from
      pathologies that cause hearing and associated language impairments in older
      children and adults. 

PMID- 24741034
TI  - Interaction of egocentric and world-centered reference frames in the rat
      posterior parietal cortex.
AB  - Navigation requires coordination of egocentric and allocentric spatial reference
      frames and may involve vectorial computations relative to landmarks. Creation of
      a representation of target heading relative to landmarks could be accomplished
      from neurons that encode the conjunction of egocentric landmark bearings with
      allocentric head direction. Landmark vector representations could then be created
      by combining these cells with distance encoding cells. Landmark vector cells have
      been identified in rodent hippocampus. Given remembered vectors at goal
      locations, it would be possible to use such cells to compute trajectories to
      hidden goals. To look for the first stage in this process, we assessed parietal
      cortical neural activity as a function of egocentric cue light location and
      allocentric head direction in rats running a random sequence to light locations
      around a circular platform. We identified cells that exhibit the predicted
      egocentric-by-allocentric conjunctive characteristics and anticipate orienting
      toward the goal. 

PMID- 24741035
TI  - Tbr2 is required to generate a neural circuit mediating the pupillary light
      reflex.
AB  - There are ~20 types of retinal ganglion cells (RGCs) in mice, each of which has
      distinct molecular, morphological, and physiological characteristics. Each RGC
      type sends axon projections to specific brain areas that execute light-dependent
      behaviors. Here, we show that the T-box transcription factor Tbr2 is required for
      the development of several RGC types that participate in non-image-forming
      circuits. These types are molecularly distinct, project to non-image-forming
      targets, and include intrinsically photosensitive RGCs. Tbr2 mutant mice have
      reduced retinal projections to non-image-forming nuclei and an attenuated
      pupillary light reflex. These data demonstrate that Tbr2 acts to execute RGC type
      choice and/or survival in a set of RGCs that mediates light-induced subconscious
      behaviors. 

PMID- 24741036
TI  - Long-term recordings improve the detection of weak excitatory-excitatory
      connections in rat prefrontal cortex.
AB  - Characterization of synaptic connectivity is essential to understanding neural
      circuit dynamics. For extracellularly recorded spike trains, indirect evidence
      for connectivity can be inferred from short-latency peaks in the correlogram
      between two neurons. Despite their predominance in cortex, however, significant
      interactions between excitatory neurons (E) have been hard to detect because of
      their intrinsic weakness. By taking advantage of long duration recordings, up to
      25 h, from rat prefrontal cortex, we found that 7.6% of the recorded pyramidal
      neurons are connected. This corresponds to ~70% of the local E-E connection
      probability that has been reported by paired intracellular recordings (11.6%).
      This value is significantly higher than previous reports from extracellular
      recordings, but still a substantial underestimate. Our analysis showed that long
      recording times and strict significance thresholds are necessary to detect weak
      connections while avoiding false-positive results, but will likely still leave
      many excitatory connections undetected. In addition, we found that hyper
      reciprocity of connections in prefrontal cortex that was shown previously by
      paired intracellular recordings was only present in short-distance, but not in
      long distance (~300 micrometers or more) interactions. As hyper-reciprocity is
      restricted to local clusters, it might be a minicolumnar effect. Given the
      current surge of interest in very high-density neural spike recording (e.g., NIH
      BRAIN Project) it is of paramount importance that we have statistically reliable
      methods for estimating connectivity from cross-correlation analysis available. We
      provide an important step in this direction. 

PMID- 24741037
TI  - Ovarian cycle effects on immediate reward selection bias in humans: a role for
      estradiol.
AB  - A variety of evidence suggests that, among humans, the individual tendency to
      choose immediate rewards ("Now") over larger, delayed rewards ("Later"), or Now
      bias, varies with frontal dopamine (DA) levels. As cyclic elevations in estradiol
      (E+) modulate other frontal DA-dependent behaviors, we tested ovarian cycle
      effects on Now bias, and whether any such effects are E+ mediated. To do so, we
      quantified Now/Later choice behavior in naturally cycling adult females (n = 87;
      ages 18-40 years) during both the menstrual phase (MP; cycle day 1-2; low E+),
      and the follicular phase (FP; cycle day 11-12; high E+). Now bias decreased an
      average of 3.6% from MP to FP (p = 0.006). Measures of salivary E+ levels at each
      visit were available in a subsample of participants (n = 34). Participants with a
      verified E+ rise from MP to FP showed significantly greater decreases in Now bias
      at mid-cycle (n = 23) than those without a rise (n = 11; p = 0.03); Now bias
      decreased an average of 10.2% in the E+ rise group but increased an average of
      7.9% in the no E+ rise group. The change in Now bias from MP to FP inversely
      correlated with the change in E+ (rho = -0.39; p = 0.023), an effect driven by
      individuals with putatively lower frontal DA based on genotype at the Val(158)Met
      polymorphism in the COMT gene. This is the first demonstration that intertemporal
      choice varies across the ovarian cycle, with Now bias declining at mid-cycle,
      when fertility peaks. Moreover, our data suggest that the interacting effects of
      estradiol and frontal DA mediate this cycle effect on decision making. 

PMID- 24741038
TI  - Rapid developmental emergence of stable depolarization during wakefulness by
      inhibitory balancing of cortical network excitability.
AB  - The ability to generate behaviorally appropriate cortical network states is
      central to sensory perception and plasticity, but little is known about the
      timing and mechanisms of their development. I paired intracellular and
      extracellular recordings in the visual cortex of awake infant rats to determine
      the synaptic and circuit mechanisms regulating the development of a key network
      state, the persistent and stable subthreshold membrane potential (Vm)
      depolarization associated with wakefulness/alertness in cortical networks, called
      the "desynchronized" or "activated" state. Current-clamp recordings reveal that
      the desynchronized state is absent during the first 2 postnatal weeks, despite
      behavioral wakefulness. During this period, Vm remains at the resting membrane
      potential >80% of the time, regardless of behavioral state. Vm dynamics during
      spontaneous or light-evoked activity were highly variable, contained long
      duration supratheshold plateau potentials, and high spike probability, suggesting
      an unstable and hyperexcitable early cortical network. Voltage-clamp recordings
      reveal that effective feedforward inhibition is absent at these early ages
      despite the presence of feedback inhibition. Stable membrane depolarization
      during wakefulness finally emerges 1-2 d before eye opening and is statistically
      indistinguishable from that in adults within days. Reduced cortical excitability,
      fast feedforward inhibition, and the slow cortical oscillation appear
      simultaneously with stable depolarization, suggesting that an absence of
      inhibitory balance during early development prevents the expression of the active
      state and hence a normal wakeful state in early cortex. These observations
      identify feedforward inhibition as a potential key regulator of cortical network
      activity development. 

PMID- 24741039
TI  - Leptin modulates the intrinsic excitability of AgRP/NPY neurons in the arcuate
      nucleus of the hypothalamus.
AB  - The hypothalamic arcuate nucleus (ARH) is a brain region critical for regulation
      of food intake and a primary area for the action of leptin in the CNS. In lean
      mice, the adipokine leptin inhibits neuropeptide Y (NPY) and agouti-related
      peptide (AgRP) neuronal activity, resulting in decreased food intake. Here we
      show that diet-induced obesity in mice is associated with persistent activation
      of NPY neurons and a failure of leptin to reduce the firing rate or hyperpolarize
      the resting membrane potential. However, the molecular mechanism whereby diet
      uncouples leptin's effect on neuronal excitability remains to be fully
      elucidated. In NPY neurons from lean mice, the Kv channel blocker 4-aminopyridine
      inhibited leptin-induced changes in input resistance and spike rate. Consistent
      with this, we found that ARH NPY neurons have a large, leptin-sensitive delayed
      rectifier K(+) current and that leptin sensitivity of this current is blunted in
      neurons from diet-induced obese mice. This current is primarily carried by Kv2
      containing channels, as the Kv2 channel inhibitor stromatoxin-1 significantly
      increased the spontaneous firing rate in NPY neurons from lean mice. In HEK
      cells, leptin induced a significant hyperpolarizing shift in the voltage
      dependence of Kv2.1 but had no effect on the function of the closely related
      channel Kv2.2 when these channels were coexpressed with the long isoform of the
      leptin receptor LepRb. Our results suggest that dynamic modulation of somatic
      Kv2.1 channels regulates the intrinsic excitability of NPY neurons to modulate
      the spontaneous activity and the integration of synaptic input onto these neurons
      in the ARH. 

PMID- 24741040
TI  - No perisaccadic mislocalization with abruptly cancelled saccades.
AB  - Every saccadic eye movement that we make changes the image of the world on our
      retina. Yet, despite these retinal shifts, we still perceive our visual world to
      be stable. Efference copy from the oculomotor system to the visual system has
      been suggested to contribute to this stable percept, enabling the brain to
      anticipate the retinal image shifts by remapping the neural image. A
      psychophysical phenomenon that has been linked to this predictive remapping is
      the mislocalization of a stimulus flashed around the time of a saccade. If this
      mislocalization is initiated by saccade preparation, one should also observe
      localization errors when a saccade is planned, but abruptly aborted just before
      its execution. We tested this hypothesis in human subjects using a novel paradigm
      that combines a flash localization task with a countermanding component that
      occasionally requires saccade cancellation. Surprisingly, we found no trace of
      mislocalization, even for saccades cancelled close to the point of no return.
      This strongly suggests that the actual execution of the saccade is a prerequisite
      for the typical localization errors, which rejects various models and constrains
      neural substrates. We conclude that perisaccadic mislocalization is not a direct
      consequence of saccade preparation, but arises after saccade execution when the
      flash location is constructed from memory. 

PMID- 24741041
TI  - Transduction without tip links in cochlear hair cells is mediated by ion channels
      with permeation properties distinct from those of the mechano-electrical
      transducer channel.
AB  - Tip links between adjacent stereocilia are believed to gate mechano-electrical
      transducer (MET) channels and mediate the electrical responses of sensory hair
      cells. We found that mouse auditory hair cells that lack tip links due to genetic
      mutations or exposure to the Ca(2+) chelator BAPTA can, however, still respond to
      mechanical stimuli. These MET currents have unusual properties and are
      predominantly of the opposite polarity relative to those measured when tip links
      are present. There are other striking differences, for example, the channels are
      usually all closed when the hair cell is not stimulated and the currents in
      response to strong stimuli can be substantially larger than normal. These
      anomalous MET currents can also be elicited early in development, before the
      onset of mechano-electrical transduction with normal response polarity. Current
      voltage curves of the anomalous MET currents are linear and do not show the
      rectification characteristic of normal MET currents. The permeant MET channel
      blocker dihydrostreptomycin is two orders of magnitude less effective in blocking
      the anomalous MET currents. The findings suggest the presence of a large
      population of MET channels with pore properties that are distinct from those of
      normal MET channels. These channels are not gated by hair-bundle links and can be
      activated under a variety of conditions in which normal tip-link-mediated
      transduction is not operational. 

PMID- 24741042
TI  - Hidden complexity of synaptic receptive fields in cat V1.
AB  - In the primary visual cortex (V1), Simple and Complex receptive fields (RFs) are
      usually characterized on the basis of the linearity of the cell spiking response
      to stimuli of opposite contrast. Whether or not this classification reflects a
      functional dichotomy in the synaptic inputs to Simple and Complex cells is still
      an open issue. Here we combined intracellular membrane potential recordings in
      cat V1 with 2D dense noise stimulation to decompose the Simple-like and Complex
      like components of the subthreshold RF into a parallel set of functionally
      distinct subunits. Results show that both Simple and Complex RFs exhibit a
      remarkable diversity of excitatory and inhibitory Complex-like contributions,
      which differ in orientation and spatial frequency selectivity from the linear RF,
      even in layer 4 and layer 6 Simple cells. We further show that the diversity of
      Complex-like contributions recovered at the subthreshold level is expressed in
      the cell spiking output. These results demonstrate that the Simple or Complex
      nature of V1 RFs does not rely on the diversity of Complex-like components
      received by the cell from its synaptic afferents but on the imbalance between the
      weights of the Simple-like and Complex-like synaptic contributions. 

PMID- 24741043
TI  - Cannabis use is quantitatively associated with nucleus accumbens and amygdala
      abnormalities in young adult recreational users.
AB  - Marijuana is the most commonly used illicit drug in the United States, but little
      is known about its effects on the human brain, particularly on reward/aversion
      regions implicated in addiction, such as the nucleus accumbens and amygdala.
      Animal studies show structural changes in brain regions such as the nucleus
      accumbens after exposure to Delta9-tetrahydrocannabinol, but less is known about
      cannabis use and brain morphometry in these regions in humans. We collected high
      resolution MRI scans on young adult recreational marijuana users and nonusing
      controls and conducted three independent analyses of morphometry in these
      structures: (1) gray matter density using voxel-based morphometry, (2) volume
      (total brain and regional volumes), and (3) shape (surface morphometry). Gray
      matter density analyses revealed greater gray matter density in marijuana users
      than in control participants in the left nucleus accumbens extending to
      subcallosal cortex, hypothalamus, sublenticular extended amygdala, and left
      amygdala, even after controlling for age, sex, alcohol use, and cigarette
      smoking. Trend-level effects were observed for a volume increase in the left
      nucleus accumbens only. Significant shape differences were detected in the left
      nucleus accumbens and right amygdala. The left nucleus accumbens showed salient
      exposure-dependent alterations across all three measures and an altered
      multimodal relationship across measures in the marijuana group. These data
      suggest that marijuana exposure, even in young recreational users, is associated
      with exposure-dependent alterations of the neural matrix of core reward
      structures and is consistent with animal studies of changes in dendritic
      arborization. 

PMID- 24741044
TI  - Myocilin is involved in NgR1/Lingo-1-mediated oligodendrocyte differentiation and
      myelination of the optic nerve.
AB  - Myocilin is a secreted glycoprotein that belongs to a family of olfactomedin
      domain-containing proteins. Although myocilin is detected in several ocular and
      nonocular tissues, the only reported human pathology related to mutations in the
      MYOCILIN gene is primary open-angle glaucoma. Functions of myocilin are poorly
      understood. Here we demonstrate that myocilin is a mediator of oligodendrocyte
      differentiation and is involved in the myelination of the optic nerve in mice.
      Myocilin is expressed and secreted by optic nerve astrocytes. Differentiation of
      optic nerve oligodendrocytes is delayed in Myocilin-null mice. Optic nerves of
      Myocilin-null mice contain reduced levels of several myelin-associated proteins
      including myelin basic protein, myelin proteolipid protein, and 2'3'-cyclic
      nucleotide 3'-phosphodiesterase compared with those of wild-type littermates.
      This leads to reduced myelin sheath thickness of optic nerve axons in Myocilin
      null mice compared with wild-type littermates, and this difference is more
      pronounced at early postnatal stages compared with adult mice. Myocilin also
      affects differentiation of oligodendrocyte precursors in vitro. Its addition to
      primary cultures of differentiating oligodendrocyte precursors increases levels
      of tested markers of oligodendrocyte differentiation and stimulates elongation of
      oligodendrocyte processes. Myocilin stimulation of oligodendrocyte
      differentiation occurs through the NgR1/Lingo-1 receptor complex. Myocilin
      physically interacts with Lingo-1 and may be considered as a Lingo-1 ligand.
      Myocilin-induced elongation of oligodendrocyte processes may be mediated by
      activation of FYN and suppression of RhoA GTPase. 

PMID- 24741045
TI  - Bridging the gap between the human and macaque connectome: a quantitative
      comparison of global interspecies structure-function relationships and network
      topology.
AB  - Resting state functional connectivity MRI (rs-fcMRI) may provide a powerful and
      noninvasive "bridge" for comparing brain function between patients and
      experimental animal models; however, the relationship between human and macaque
      rs-fcMRI remains poorly understood. Here, using a novel surface deformation
      process for species comparisons in the same anatomical space (Van Essen, 2004,
      2005), we found high correspondence, but also unique hub topology, between human
      and macaque functional connectomes. The global functional connectivity match
      between species was moderate to strong (r = 0.41) and increased when considering
      the top 15% strongest connections (r = 0.54). Analysis of the match between
      functional connectivity and the underlying anatomical connectivity, derived from
      a previous retrograde tracer study done in macaques (Markov et al., 2012), showed
      impressive structure-function correspondence in both the macaque and human. When
      examining the strongest structural connections, we found a 70-80% match between
      structural and functional connectivity matrices in both species. Finally, we
      compare species on two widely used metrics for studying hub topology: degree and
      betweenness centrality. The data showed topological agreement across the species,
      with nodes of the posterior cingulate showing high degree and betweenness
      centrality. In contrast, nodes in medial frontal and parietal cortices were
      identified as having high degree and betweenness in the human as opposed to the
      macaque. Our results provide: (1) a thorough examination and validation for a
      surface-based interspecies deformation process, (2) a strong theoretical
      foundation for making interspecies comparisons of rs-fcMRI, and (3) a unique look
      at topological distinctions between the species. 

PMID- 24741046
TI  - Vocal generalization depends on gesture identity and sequence.
AB  - Generalization, the brain's ability to transfer motor learning from one context
      to another, occurs in a wide range of complex behaviors. However, the rules of
      generalization in vocal behavior are poorly understood, and it is unknown how
      vocal learning generalizes across an animal's entire repertoire of natural
      vocalizations and sequences. Here, we asked whether generalization occurs in a
      nonhuman vocal learner and quantified its properties. We hypothesized that
      adaptive error correction of a vocal gesture produced in one sequence would
      generalize to the same gesture produced in other sequences. To test our
      hypothesis, we manipulated the fundamental frequency (pitch) of auditory feedback
      in Bengalese finches (Lonchura striata var. domestica) to create sensory errors
      during vocal gestures (song syllables) produced in particular sequences. As
      hypothesized, error-corrective learning on pitch-shifted vocal gestures
      generalized to the same gestures produced in other sequential contexts.
      Surprisingly, generalization magnitude depended strongly on sequential distance
      from the pitch-shifted syllables, with greater adaptation for gestures produced
      near to the pitch-shifted syllable. A further unexpected result was that
      nonshifted syllables changed their pitch in the direction opposite from the
      shifted syllables. This apparently antiadaptive pattern of generalization could
      not be explained by correlations between generalization and the acoustic
      similarity to the pitch-shifted syllable. These findings therefore suggest that
      generalization depends on the type of vocal gesture and its sequential context
      relative to other gestures and may reflect an advantageous strategy for vocal
      learning and maintenance. 

PMID- 24741047
TI  - Biphasic mechanisms of amphetamine action at the dopamine terminal.
AB  - In light of recent studies suggesting that amphetamine (AMPH) increases
      electrically evoked dopamine release ([DA]o), we examined discrepancies between
      these findings and literature that has demonstrated AMPH-induced decreases in
      [DA]o. The current study has expanded the inventory of AMPH actions by defining
      two separate mechanisms of AMPH effects on [DA]o at high and low doses, one
      dopamine transporter (DAT) independent and one DAT dependent, respectively. AMPH
      concentrations were measured via microdialysis in rat nucleus accumbens after
      intraperitoneal injections of 1 and 10 mg/kg and yielded values of ~10 and 200
      nM, respectively. Subsequently, voltammetry in brain slices was used to examine
      the effects of low (10 nM), moderate (100 nM), and high (10 MUM) concentrations
      of AMPH across a range of frequency stimulations (one pulse; five pulses, 20 Hz;
      24 pulses, 60 Hz). We discovered biphasic, concentration-dependent effects in WT
      mice, in which AMPH increased [DA]o at low concentrations and decreased [DA]o at
      high concentrations across all stimulation types. However, in slices from DAT-KO
      mice, [DA]o was decreased by all concentrations of AMPH, demonstrating that AMPH
      induced increases in [DA]o are DAT dependent, whereas the decreases at high
      concentrations are DAT independent. We propose that low AMPH concentrations are
      insufficient to disrupt vesicular sequestration, and therefore AMPH acts solely
      as a DAT inhibitor to increase [DA]o. When AMPH concentrations are high, the
      added mechanism of vesicular depletion leads to reduced [DA]o. The biphasic
      mechanisms observed here confirm and extend the traditional actions of AMPH, but
      do not support mechanisms involving increased exocytotic release.

PMID- 24741048
TI  - A neural code for looming and receding motion is distributed over a population of
      electrosensory ON and OFF contrast cells.
AB  - Object saliency is based on the relative local-to-background contrast in the
      physical signals that underlie perceptual experience. As such, contrast-detecting
      neurons (ON/OFF cells) are found in many sensory systems, responding respectively
      to increased or decreased intensity within their receptive field centers. This
      differential sensitivity suggests that ON and OFF cells initiate segregated
      streams of information for positive and negative sensory contrast. However, while
      recording in vivo from the ON and OFF cells of Apteronotus leptorhynchus, we
      report that the reversal of stimulus motion triggers paradoxical responses to
      electrosensory contrast. By considering the instantaneous firing rates of both ON
      and OFF cell populations, a bidirectionally symmetric representation of motion is
      achieved for both positive and negative contrast stimuli. Whereas the firing
      rates of the individual contrast detecting neurons convey scalar information,
      such as object distance, it is their sequential activation over longer timescales
      that track changes in the direction of movement. 

PMID- 24741049
TI  - Neural mechanisms of gain-loss asymmetry in temporal discounting.
AB  - Humans typically discount future gains more than losses. This phenomenon is
      referred to as the "sign effect" in experimental and behavioral economics.
      Although recent studies have reported associations between the sign effect and
      important social problems, such as obesity and incurring multiple debts, the
      biological basis for this phenomenon remains poorly understood. Here, we
      hypothesized that enhanced loss-related neural processing in magnitude and/or
      delay representation are causes of the sign effect. We examined participants
      performing intertemporal choice tasks involving future gains or losses and
      compared the brain activity of those who exhibited the sign effect and those who
      did not. When predicting future losses, significant differences were apparent
      between the two participant groups in terms of striatal activity representing
      delay length and in insular activity representing sensitivity to magnitude.
      Furthermore, participants with the sign effect exhibited a greater insular
      response to the magnitude of loss than to that of gain, and also a greater
      striatal response to the delay of loss than to that of gain. These findings may
      provide a new biological perspective for the development of novel treatments and
      preventive measures for social problems associated with the sign effect. 

PMID- 24741050
TI  - TMS-EEG signatures of GABAergic neurotransmission in the human cortex.
AB  - Combining transcranial magnetic stimulation (TMS) and electroencephalography
      (EEG) constitutes a powerful tool to directly assess human cortical excitability
      and connectivity. TMS of the primary motor cortex elicits a sequence of TMS
      evoked EEG potentials (TEPs). It is thought that inhibitory neurotransmission
      through GABA-A receptors (GABAAR) modulates early TEPs (<50 ms after TMS),
      whereas GABA-B receptors (GABABR) play a role for later TEPs (at ~100 ms after
      TMS). However, the physiological underpinnings of TEPs have not been clearly
      elucidated yet. Here, we studied the role of GABAA/B-ergic neurotransmission for
      TEPs in healthy subjects using a pharmaco-TMS-EEG approach. In Experiment 1, we
      tested the effects of a single oral dose of alprazolam (a classical
      benzodiazepine acting as allosteric-positive modulator at alpha1, alpha2, alpha3,
      and alpha5 subunit-containing GABAARs) and zolpidem (a positive modulator mainly
      at the alpha1 GABAAR) in a double-blind, placebo-controlled, crossover study. In
      Experiment 2, we tested the influence of baclofen (a GABABR agonist) and diazepam
      (a classical benzodiazepine) versus placebo on TEPs. Alprazolam and diazepam
      increased the amplitude of the negative potential at 45 ms after stimulation
      (N45) and decreased the negative component at 100 ms (N100), whereas zolpidem
      increased the N45 only. In contrast, baclofen specifically increased the N100
      amplitude. These results provide strong evidence that the N45 represents activity
      of alpha1-subunit-containing GABAARs, whereas the N100 represents activity of
      GABABRs. Findings open a novel window of opportunity to study alteration of GABAA
      /GABAB-related inhibition in disorders, such as epilepsy or schizophrenia. 

PMID- 24741051
TI  - Neuroanatomical profiles of deafness in the context of native language
      experience.
AB  - The study of congenitally deaf adult humans provides an opportunity to examine
      neuroanatomical plasticity resulting from altered sensory experience. However,
      attributing the source of the brain's structural variance in the deaf is
      complicated by the fact that deaf individuals also differ in their language
      experiences (e.g., sign vs spoken), which likely influence brain anatomy
      independently. Although the majority of deaf individuals in the United States are
      born to hearing parents and are exposed to English, not American Sign Language
      (ASL) as their first language, most studies on deafness have been conducted with
      deaf native users of ASL (deaf signers). This raises the question of whether
      observations made in deaf signers can be generalized. Using a factorial design,
      we compared gray (GMV) and white (WMV) matter volume in deaf and hearing native
      users of ASL, as well as deaf and hearing native users of English. Main effects
      analysis of sensory experience revealed less GMV in the deaf groups combined
      (compared with hearing groups combined) in early visual areas and less WMV in a
      left early auditory region. The interaction of sensory experience and language
      experience revealed that deaf native users of English had fewer areas of
      anatomical differences than did deaf native users of ASL (each compared with
      their hearing counterparts). For deaf users of ASL specifically, WMV differences
      resided in language areas such as the left superior temporal and inferior frontal
      regions. Our results demonstrate that cortical plasticity resulting from deafness
      depends on language experience and that findings from native signers cannot be
      generalized. 

PMID- 24741052
TI  - Different neuronal computations of spatial working memory for multiple locations
      within versus across visual hemifields.
AB  - Spatial working memory is one of the most studied cognitive functions, serving as
      a model system to decipher computational principles of the brain. Although
      neuronal mechanisms for remembering a single location have been well elucidated,
      little is known about memory for multiple locations. Here, we examined the
      activities of prefrontal neurons during monkeys remembered positions of one or
      two visual cue(s). When the two cues were presented across the left and right
      visual fields, neurons exhibited a comparable response to the activity for the
      preferred cue presented alone. When the two cues were presented within the same
      hemifield, neurons exhibited an intermediate response between those to the
      individual cues. Subsequent computer simulations predicted a lower signal-to
      noise ratio in the latter condition, which was further verified by behavioral
      experiments. Considering the separation of contralateral and ipsilateral visual
      processing, the lateral inhibition in local circuits might implicitly determine
      different neuronal computations and memory capacities for bilateral and
      unilateral displays. 

PMID- 24741053
TI  - Mechanisms of coordination in distributed neural circuits: encoding coordinating
      information.
AB  - We describe synaptic connections through which information essential for encoding
      efference copies reaches two coordinating neurons in each of the microcircuits
      that controls limbs on abdominal segments of the crayfish, Pacifastacus
      leniusculus. In each microcircuit, these coordinating neurons fire bursts of
      spikes simultaneously with motor neurons. These bursts encode timing, duration,
      and strength of each motor burst. Using paired microelectrode recordings, we
      demonstrate that one class of nonspiking neurons in each microcircuit's pattern
      generating kernel--IPS--directly inhibits the ASCE coordinating neuron that
      copies each burst in power-stroke (PS) motor neurons. This inhibitory synapse
      parallels IPS's inhibition of the same PS motor neurons. Using a disynaptic
      pathway to control its membrane potential, we demonstrate that a second type of
      nonspiking interneuron in the pattern-generating kernel--IRSh--inhibits the DSC
      coordinating neuron that copies each burst in return-stroke (RS) motor neurons.
      This inhibitory synapse parallels IRS's inhibition of the microcircuit's RS motor
      neurons. Experimental changes in the membrane potential of one IPS or one IRSh
      neuron simultaneously changed the strengths of motor bursts, durations, numbers
      of spikes, and spike frequency in the simultaneous ASCE and DSC bursts. ASCE and
      DSC coordinating neurons link the segmentally distributed microcircuits into a
      coordinated system that oscillates with the same period and with stable phase
      differences. The inhibitory synapses from different pattern-generating neurons
      that parallel their inhibition of different sets of motor neurons enable ASCE and
      DSC to encode details of each oscillation that are necessary for stable, adaptive
      synchronization of the system.

PMID- 24741054
TI  - Predictive saccade target selection in superior colliculus during visual search.
AB  - Searching for a visual object naturally involves sequences of gaze fixations,
      during which the current foveal image is analyzed and the next object to inspect
      is selected as a saccade target. Fixation durations during such sequences are
      short, suggesting that saccades may be concurrently processed. Therefore, the
      selection of the next saccade target may occur before the current saccade target
      is acquired. To test this hypothesis, we trained four female rhesus monkeys
      (Macaca mulatta) to perform a multiple-fixation visual conjunction search task.
      We simultaneously recorded the activity of sensorimotor neurons in the midbrain
      superior colliculus (SC) in two monkeys. In this task, monkeys made multiple
      fixations before foveating the target. Fixation durations were significantly
      shorter than the latency of the initial responses to the search display, with
      approximately one-quarter being shorter than the shortest response latencies. The
      time at which SC sensorimotor activity discriminated the target from distracters
      occurred significantly earlier for the selection of subsequent fixations than for
      the selection of the first fixation. Target selection during subsequent fixations
      occurred even before the visual afferent delay in more than half of the neuronal
      sample, suggesting that the process of selection can encompass at least two
      future saccade targets. This predictive selection was present even when
      differences in saccade latencies were taken into account. Altogether, these
      findings demonstrate how neural representations on the visual salience map are
      processed in parallel, thus facilitating visual search. 

PMID- 24741056
TI  - Suppression of salient objects prevents distraction in visual search.
AB  - To find objects of interest in a cluttered and continually changing visual
      environment, humans must often ignore salient stimuli that are not currently
      relevant to the task at hand. Recent neuroimaging results indicate that the
      ability to prevent salience-driven distraction depends on the current level of
      attentional control activity in frontal cortex, but the specific mechanism by
      which this control activity prevents salience-driven distraction is still poorly
      understood. Here, we asked whether salience-driven distraction is prevented by
      suppressing salient distractors or by preferentially up-weighting the relevant
      visual dimension. We found that salient distractors were suppressed even when
      they resided in the same feature dimension as the target (that is, when
      dimensional weighting was not a viable selection strategy). Our
      neurophysiological measure of suppression--the PD component of the event-related
      potential--was associated with variations in the amount of time it took to
      perform the search task: distractors triggered the PD on fast-response trials,
      but on slow-response trials they triggered activity associated with working
      memory representation instead. These results demonstrate that during search
      salience-driven distraction is mitigated by a suppressive mechanism that reduces
      the salience of potentially distracting visual objects.

PMID- 24741055
TI  - Synaptic glutamate spillover due to impaired glutamate uptake mediates heroin
      relapse.
AB  - Reducing the enduring vulnerability to relapse is a therapeutic goal in treating
      drug addiction. Studies with animal models of drug addiction show a marked
      increase in extrasynaptic glutamate in the core subcompartment of the nucleus
      accumbens (NAcore) during reinstated drug seeking. However, the synaptic
      mechanisms linking drug-induced changes in extrasynaptic glutamate to relapse are
      poorly understood. Here, we discovered impaired glutamate elimination in rats
      extinguished from heroin self-administration that leads to spillover of
      synaptically released glutamate into the nonsynaptic extracellular space in
      NAcore and investigated whether restoration of glutamate transport prevented
      reinstated heroin seeking. Through multiple functional assays of glutamate uptake
      and analyzing NMDA receptor-mediated currents, we show that heroin self
      administration produced long-lasting downregulation of glutamate uptake and
      surface expression of the transporter GLT-1. This downregulation was associated
      with spillover of synaptic glutamate to extrasynaptic NMDA receptors within the
      NAcore. Ceftriaxone restored glutamate uptake and prevented synaptic glutamate
      spillover and cue-induced heroin seeking. Ceftriaxone-induced inhibition of
      reinstated heroin seeking was blocked by morpholino-antisense targeting GLT-1
      synthesis. These data reveal that the synaptic glutamate spillover in the NAcore
      results from reduced glutamate transport and is a critical pathophysiological
      mechanism underling reinstated drug seeking in rats extinguished from heroin self
      administration. 

PMID- 24741057
TI  - Mapping the perceptual grain of the human retina.
AB  - In humans, experimental access to single sensory receptors is difficult to
      achieve, yet it is crucial for learning how the signals arising from each
      receptor are transformed into perception. By combining adaptive optics
      microstimulation with high-speed eye tracking, we show that retinal function can
      be probed at the level of the individual cone photoreceptor in living eyes.
      Classical psychometric functions were obtained from cone-sized microstimuli
      targeted to single photoreceptors. Revealed psychophysically, the cone mosaic
      also manifests a variable sensitivity to light across its surface that accords
      with a simple model of cone light capture. Because this microscopic grain of
      vision could be detected on the perceptual level, it suggests that photoreceptors
      can act individually to shape perception, if the normally suboptimal relay of
      light by the eye's optics is corrected. Thus the precise arrangement of cones and
      the exact placement of stimuli onto those cones create the initial retinal limits
      on signals mediating spatial vision. 

PMID- 24741058
TI  - Dynamic neural correlates of motor error monitoring and adaptation during trial
      to-trial learning.
AB  - A basic EEG feature upon voluntary movements in healthy human subjects is a beta
      (13-30 Hz) band desynchronization followed by a postmovement event-related
      synchronization (ERS) over contralateral sensorimotor cortex. The functional
      implications of these changes remain unclear. We hypothesized that, because beta
      ERS follows movement, it may reflect the degree of error in that movement, and
      the salience of that error to the task at hand. As such, the signal might
      underpin trial-to-trial modifications of the internal model that informs future
      movements. To test this hypothesis, EEG was recorded in healthy subjects while
      they moved a joystick-controlled cursor to visual targets on a computer screen,
      with different rotational perturbations applied between the joystick and cursor.
      We observed consistently lower beta ERS in trials with large error, even when
      other possible motor confounds, such as reaction time, movement duration, and
      path length, were controlled, regardless of whether the perturbation was random
      or constant. There was a negative trial-to-trial correlation between the size of
      the absolute initial angular error and the amplitude of the beta ERS, and this
      negative correlation was enhanced when other contextual information about the
      behavioral salience of the angular error, namely, the bias and variance of errors
      in previous trials, was additionally considered. These same features also had an
      impact on the behavioral performance. The findings suggest that the beta ERS
      reflects neural processes that evaluate motor error and do so in the context of
      the prior history of errors. 

PMID- 24741059
TI  - The impact of cortical deafferentation on the neocortical slow oscillation.
AB  - Slow oscillation is the main brain rhythm observed during deep sleep in mammals.
      Although several studies have demonstrated its neocortical origin, the extent of
      the thalamic contribution is still a matter of discussion. Using
      electrophysiological recordings in vivo on cats and computational modeling, we
      found that the local thalamic inactivation or the complete isolation of the
      neocortical slabs maintained within the brain dramatically reduced the expression
      of slow and fast oscillations in affected cortical areas. The slow oscillation
      began to recover 12 h after thalamic inactivation. The slow oscillation, but not
      faster activities, nearly recovered after 30 h and persisted for weeks in the
      isolated slabs. We also observed an increase of the membrane potential
      fluctuations recorded in vivo several hours after thalamic inactivation.
      Mimicking this enhancement in a network computational model with an increased
      postsynaptic activity of long-range intracortical afferents or scaling K(+) leak
      current, but not several other Na(+) and K(+) intrinsic currents was sufficient
      for recovering the slow oscillation. We conclude that, in the intact brain, the
      thalamus contributes to the generation of cortical active states of the slow
      oscillation and mediates its large-scale synchronization. Our study also suggests
      that the deafferentation-induced alterations of the sleep slow oscillation can be
      counteracted by compensatory intracortical mechanisms and that the sleep slow
      oscillation is a fundamental and intrinsic state of the neocortex. 

PMID- 24741060
TI  - Limb and trunk mechanisms for balance control during locomotion in quadrupeds.
AB  - In quadrupeds, the most critical aspect of postural control during locomotion is
      lateral stability. However, neural mechanisms underlying lateral stability are
      poorly understood. Here, we studied lateral stability in decerebrate cats walking
      on a treadmill with their hindlimbs. Two destabilizing factors were used: a brief
      lateral push of the cat and a sustained lateral tilt of the treadmill. It was
      found that the push caused considerable trunk bending and twisting, as well as
      changes in the stepping pattern, but did not lead to falling. Due to postural
      reactions, locomotion with normal body configuration was restored in a few steps.
      It was also found that the decerebrate cat could keep balance during locomotion
      on the laterally tilted treadmill. This postural adaptation was based on the
      transformation of the symmetrical locomotor pattern into an asymmetrical one,
      with different functional lengths of the right and left limbs. Then, we analyzed
      limb and trunk neural mechanisms contributing to postural control during
      locomotion. It was found that one of the limb mechanisms operates in the transfer
      phase and secures a standard (relative to the trunk) position for limb landing.
      Two other limb mechanisms operate in the stance phase; they counteract
      distortions of the locomotor pattern by regulating the limb stiffness. The trunk
      configuration mechanism controls the body shape on the basis of sensory
      information coming from trunk afferents. We suggest that postural reactions
      generated by these four mechanisms are integrated, thus forming a response of the
      whole system to perturbation of balance during locomotion. 

PMID- 24741061
TI  - Robo1 modulates proliferation and neurogenesis in the developing neocortex.
AB  - The elaborate cytoarchitecture of the mammalian neocortex requires the timely
      production of its constituent pyramidal neurons and interneurons and their
      disposition in appropriate layers. Numerous chemotropic factors present in the
      forebrain throughout cortical development play important roles in the
      orchestration of these events. The Roundabout (Robo) family of receptors and
      their ligands, the Slit proteins, are expressed in the developing forebrain, and
      are known to play important roles in the generation and migration of cortical
      interneurons. However, few studies have investigated their function(s) in the
      development of pyramidal cells. Here, we observed expression of Robo1 and Slit
      genes (Slit1, Slit2) in cells lining the telencephalic ventricles, and found
      significant increases in progenitor cells (basal and apical) at embryonic day
      (E)12.5 and E14.5 in the developing cortex of Robo1(-/-), Slit1(-/-), and Slit1(
      /-)/Slit2(-/-), but not in mice lacking the other Robo or Slit genes. Using layer
      specific markers, we found that both early- and late-born pyramidal neuron
      populations were significantly increased in the cortices of Robo1(-/-) mice at
      the end of corticogenesis (E18.5). The excess number of cortical pyramidal
      neurons generated prenatally appears to die in early postnatal life. The observed
      increase in pyramidal neurons was due to prolonged proliferative activity of
      their progenitors and not due to changes in cell cycle events. This finding,
      confirmed by in utero electroporation with Robo1 short hairpin RNA (shRNA) or
      control constructs into progenitors along the ventricular zone as well as in
      dissociated cortical cell cultures, points to a novel role for Robo1 in
      regulating the proliferation and generation of pyramidal neurons. 

PMID- 24741062
TI  - Author-initiated retraction: Li et al., Elevation of brain magnesium prevents and
      reverses cognitive deficits and synaptic loss in Alzheimer's disease mouse model.

PMID- 24741063
TI  - White matter connections of the supplementary motor area in humans.
AB  - INTRODUCTION: The supplementary motor area (SMA) is frequently involved by brain
      tumours (particularly WHO grade II gliomas). Surgery in this area can be followed
      by the 'SMA syndrome', characterised by contralateral akinesia and mutism.
      Knowledge of the connections of the SMA can provide new insights on the genesis
      of the SMA syndrome, and a better understanding of the challenges related to
      operating in this region. METHODS: White matter connections of the SMA were
      studied with both postmortem dissection and advance diffusion imaging
      tractography. Postmortem dissections were performed according to the Klingler
      technique. 12 specimens were fixed in 10% formalin and frozen at -15 degrees C
      for 2 weeks. After thawing, dissection was performed with blunt dissectors. For
      diffusion tractography, high-resolution diffusion imaging datasets from 10 adult
      healthy controls from the Human Connectome Project database were used. Whole
      brain tractography was performed using a spherical deconvolution approach.
      RESULTS: Five main connections were identified in both postmortem dissections and
      tractography reconstructions: (1) U-fibres running in the precentral sulcus,
      connecting the precentral gyrus and the SMA; (2) U-fibres running in the
      cingulate sulcus, connecting the SMA with the cingulate gyrus; (3) frontal
      'aslant' fascicle, directly connecting the SMA with the pars opercularis of the
      inferior frontal gyrus; (4) medial fibres connecting the SMA with the striatum;
      and (5) SMA callosal fibres. Good concordance was observed between postmortem
      dissections and diffusion tractography. CONCLUSIONS: The SMA shows a wide range
      of white matter connections with motor, language and lymbic areas. Features of
      the SMA syndrome (akinesia and mutism) can be better understood on the basis of
      these findings.

PMID- 24741064
TI  - Cerebral tau is elevated after aneurysmal subarachnoid haemorrhage and associated
      with brain metabolic distress and poor functional and cognitive long-term
      outcome.
AB  - BACKGROUND: Recent evidence suggests axonal injury after aneurysmal subarachnoid
      haemorrhage (aSAH). The microtubule-associated protein, tau, has been shown to be
      elevated in the cerebrospinal fluid after aSAH, however, brain extracellular tau
      levels and their relation to long-term neurological and cognitive outcomes have
      not been investigated. METHODS: Serial cerebral microdialysis (CMD) samples were
      collected from 22 consecutive aSAH patients with multimodal neuromonitoring to
      determine CMD-total-tau by ELISA. CMD-total-tau was analysed considering other
      brain metabolic parameters, brain tissue oxygen tension (PbtO2), and functional
      and neuropsychological outcome at 12 months. All outcome models were analysed
      using generalised estimating equations with an autoregressive working correlation
      matrix to account for multiple measurements of brain extracellular proteins per
      subject. RESULTS: CMD-total-tau levels positively correlated with brain
      extracellular fluid levels of lactate (r=0.40, p<0.001), glutamate (r=0.45,
      p<0.001), pyruvate (r=0.26, p<0.001), and the lactate-pyruvate ratio (r=0.26,
      p<0.001), and were higher in episodes of hypoxic (PbtO2<20 mm Hg) brain
      extracellular lactate elevation (>4 mmol/L) (p<0.01). More importantly, high CMD
      total-tau levels were associated with poor functional outcome (modified Rankin
      Scale >=4) 12 months after aSAH even after adjusting for disease severity and age
      (p=0.001). A similar association was found with 3/5 neuropsychological tests
      indicative of impairments in cognition, psychomotor speed, visual
      conceptualisation and frontal executive functions at 1 year after aSAH (p<0.01).
      CONCLUSIONS: These results suggest that CMD-total tau may be an important
      biomarker for predicting long-term outcome in patients with severe aSAH. The
      value of axonal injury needs further confirmation in a larger patient cohort,
      preferably combined with advanced imaging techniques.

PMID- 24741065
TI  - S. pombe TORC1 activates the ubiquitin-proteasomal degradation of the meiotic
      regulator Mei2 in cooperation with Pat1 kinase.
AB  - Target of rapamycin (TOR) kinase regulates cell metabolism and growth, acting as
      a subunit of two multi-protein complexes, TORC1 and TORC2. Known TORC substrates
      are either kinases or general factors involved in growth control. Here, we show
      that fission yeast TORC1, which promotes vegetative growth and suppresses sexual
      development, can phosphorylate Mei2 (a specific factor involved in switching the
      cell fate) in vitro. Alanine substitutions at the nine Mei2 phosphorylation sites
      stabilize the protein and promote mating and meiosis in vivo. We found that Mei2
      is polyubiquitylated in vivo in a TORC1-dependent manner. Based on these data, we
      propose that TORC1 contributes to the suppression of sexual development by
      phosphorylating Mei2, in addition to controlling the cellular metabolic status. 

PMID- 24741066
TI  - Interphase phosphorylation of lamin A.
AB  - Nuclear lamins form the major structural elements that comprise the nuclear
      lamina. Loss of nuclear structural integrity has been implicated as a key factor
      in the lamin A/C gene mutations that cause laminopathies, whereas the normal
      regulation of lamin A assembly and organization in interphase cells is still
      undefined. We assumed phosphorylation to be a major determinant, identifying 20
      prime interphase phosphorylation sites, of which eight were high-turnover sites.
      We examined the roles of these latter sites by site-directed mutagenesis,
      followed by detailed microscopic analysis - including fluorescence recovery after
      photobleaching, fluorescence correlation spectroscopy and nuclear extraction
      techniques. The results reveal three phosphorylation regions, each with dominant
      sites, together controlling lamin A structure and dynamics. Interestingly, two of
      these interphase sites are hyper-phosphorylated in mitotic cells and one of these
      sites is within the sequence that is missing in progerin of the Hutchinson
      Gilford progeria syndrome. We present a model where different phosphorylation
      combinations yield markedly different effects on the assembly, subunit turnover
      and the mobility of lamin A between, and within, the lamina, the nucleoplasm and
      the cytoplasm of interphase cells. 

PMID- 24741067
TI  - Cadherin-11 regulates both mesenchymal stem cell differentiation into smooth
      muscle cells and the development of contractile function in vivo.
AB  - Although soluble factors, such as transforming growth factor beta1 (TGF-beta1),
      induce mesenchymal stem cell (MSC) differentiation towards the smooth muscle cell
      (SMC) lineage, the role of adherens junctions in this process is not well
      understood. In this study, we found that cadherin-11 but not cadherin-2 was
      necessary for MSC differentiation into SMCs. Cadherin-11 regulated the expression
      of TGF-beta1 and affected SMC differentiation through a pathway that was
      dependent on TGF-beta receptor II (TGFbetaRII) but independent of SMAD2 or SMAD3.
      In addition, cadherin-11 activated the expression of serum response factor (SRF)
      and SMC proteins through the Rho-associated protein kinase (ROCK) pathway.
      Engagement of cadherin-11 increased its own expression through SRF, indicative of
      the presence of an autoregulatory feedback loop that committed MSCs to the SMC
      fate. Notably, SMC-containing tissues (such as aorta and bladder) from cadherin
      11-null (Cdh11(-/-)) mice showed significantly reduced levels of SMC proteins and
      exhibited diminished contractility compared with controls. This is the first
      report implicating cadherin-11 in SMC differentiation and contractile function in
      vitro as well as in vivo. 

PMID- 24741068
TI  - The malignancy of metastatic ovarian cancer cells is increased on soft matrices
      through a mechanosensitive Rho-ROCK pathway.
AB  - Although current treatments for localized ovarian cancer are highly effective,
      this cancer still remains the most lethal gynecological malignancy, largely owing
      to the fact that it is often detected only after tumor cells leave the primary
      tumor. Clinicians have long noted a clear predilection for ovarian cancer to
      metastasize to the soft omentum. Here, we show that this tropism is due not only
      to chemical signals but also mechanical cues. Metastatic ovarian cancer cells
      (OCCs) preferentially adhere to soft microenvironments and display an enhanced
      malignant phenotype, including increased migration, proliferation and
      chemoresistance. To understand the cell-matrix interactions that are used to
      sense the substrate rigidity, we utilized traction force microscopy (TFM) and
      found that, on soft substrates, human OCCs increased both the magnitude of
      traction forces as well as their degree of polarization. After culture on soft
      substrates, cells underwent morphological elongation characteristic of epithelial
      to-mesenchymal transition (EMT), which was confirmed by molecular analysis.
      Consistent with the idea that mechanical cues are a key determinant in the spread
      of ovarian cancer, the observed mechanosensitivity was greatly decreased in less
      metastatic OCCs. Finally, we demonstrate that this mechanical tropism is governed
      through a Rho-ROCK signaling pathway. 

PMID- 24741069
TI  - The dynamics of MAPK inactivation at fertilization in mouse eggs.
AB  - Egg activation at fertilization in mammals is initiated by prolonged Ca(2+)
      oscillations that trigger the completion of meiosis and formation of pronuclei. A
      fall in mitogen-activated protein kinase (MAPK) activity is essential for
      pronuclear formation, but the precise timing and mechanism of decline are
      unknown. Here, we have measured the dynamics of MAPK pathway inactivation during
      fertilization of mouse eggs using novel chemiluminescent MAPK activity reporters.
      This reveals that the MAPK activity decrease begins during the Ca(2+)
      oscillations, but MAPK does not completely inactivate until after pronuclear
      formation. The MAPKs present in eggs are Mos, MAP2K1 and MAP2K2 (MEK1 and MEK2,
      respectively) and MAPK3 and MAPK1 (ERK1 and ERK2, respectively). Notably, the
      MAPK activity decline at fertilization is not explained by upstream destruction
      of Mos, because a decrease in the signal from a Mos-luciferase reporter is not
      associated with egg activation. Furthermore, Mos overexpression does not affect
      the timing of MAPK inactivation or pronuclear formation. However, the late
      decrease in MAPK could be rapidly reversed by the protein phosphatase inhibitor,
      okadaic acid. These data suggest that the completion of meiosis in mouse zygotes
      is driven by an increased phosphatase activity and not by a decline in Mos levels
      or MEK activity. 

PMID- 24741070
TI  - Hypoxemia-induced leptin secretion: a mechanism for the control of food intake in
      diseased fish.
AB  - Leptin is a potent anorexigen, but little is known about the physiological
      conditions under which this cytokine regulates food intake in fish. In this
      study, we characterized the relationships between food intake, O2-carrying
      capacity, liver leptin-A1 (lep-a1) gene expression, and plasma leptin-A1 in
      rainbow trout infected with a pathogenic hemoflagellate, Cryptobia salmositica.
      As lep gene expression is hypoxia-sensitive and Cryptobia-infected fish are
      anemic, we hypothesized that Cryptobia-induced anorexia is mediated by leptin. A
      14-week time course experiment revealed that Cryptobia-infected fish experience a
      transient 75% reduction in food intake, a sharp initial drop in hematocrit and
      hemoglobin levels followed by a partial recovery, a transient 17-fold increase in
      lep-a1 gene expression, and a sustained increase in plasma leptin-A1 levels. In
      the hypothalamus, peak anorexia was associated with decreases in mRNA levels of
      neuropeptide Y (npy) and cocaine- and amphetamine-regulated transcript (cart),
      and increases in agouti-related protein (agrp) and pro-opiomelanocortin A2
      (pomc). In contrast, in non-infected fish pair-fed to infected animals, lep-a1
      gene expression and plasma levels did not differ from those of non-infected
      satiated fish. Pair-fed fish were also characterized by increases in hypothalamic
      npy and agrp, no changes in pomc-a2, and a reduction in cart mRNA expression.
      Finally, peak infection was characterized by a significant positive correlation
      between O2-carrying capacity and food intake. These findings show that hypoxemia,
      and not feed restriction, stimulates leptin-A1 secretion in Cryptobia-infected
      rainbow trout and suggest that leptin contributes to anorexia by inhibiting
      hypothalamic npy and stimulating pomc-a2. 

PMID- 24741071
TI  - Mex3c mutation reduces adiposity partially through increasing physical activity.
AB  - MEX3C is an RNA-binding protein with unknown physiological function. We have
      recently reported that a Mex3c mutation in mice causes growth retardation and
      reduced adiposity, but how adiposity is reduced remains unclear. Herein, we show
      that homozygous Mex3c gene trap mice have increased physical activity. The Mex3c
      mutation consistently conferred full protection from diet-induced obesity,
      hyperglycemia, insulin resistance, hyperlipidemia, and hepatic steatosis. In
      ob/ob mice with leptin deficiency, the Mex3c mutation also increased physical
      activity and improved glucose and lipid profiles. Expressing cre in the neurons
      of Mex3c gene trap mice, an attempt to partially restoring neuronal Mex3c
      expression, significantly increased white adipose tissue deposition, but had no
      effects on body length. Our data suggest that one way in which Mex3c regulates
      adiposity is through controlling physical activity, and that neuronal Mex3c
      expression could play an important role in this process. 

PMID- 24741072
TI  - Development of mammalian ovary.
AB  - Pre-natal and early post-natal ovarian development has become a field of
      increasing importance over recent years. The full effects of perturbations of
      ovarian development on adult fertility, through environmental changes or genetic
      anomalies, are only now being truly appreciated. Mitigation of these
      perturbations requires an understanding of the processes involved in the
      development of the ovary. Herein, we review some recent findings from mice,
      sheep, and cattle on the key events involved in ovarian development. We discuss
      the key process of germ cell migration, ovigerous cord formation, meiosis, and
      follicle formation and activation. We also review the key contributions of
      mesonephric cells to ovarian development and propose roles for these cells.
      Finally, we discuss polycystic ovary syndrome, premature ovarian failure, and pre
      natal undernutrition; three key areas in which perturbations to ovarian
      development appear to have major effects on post-natal fertility. 

PMID- 24741073
TI  - Exposure to excess insulin (glargine) induces type 2 diabetes mellitus in mice
      fed on a chow diet.
AB  - We have previously shown that insulin plays an important role in the nutrient
      induced insulin resistance. In this study, we tested the hypothesis that chronic
      exposure to excess long-acting insulin (glargine) can cause typical type 2
      diabetes mellitus (T2DM) in normal mice fed on a chow diet. C57BL/6 mice were
      treated with glargine once a day for 8 weeks, followed by evaluations of food
      intake, body weight, blood levels of glucose, insulin, lipids, and cytokines,
      insulin signaling, histology of pancreas, ectopic fat accumulation, oxidative
      stress level, and cholesterol content in mitochondria in tissues. Cholesterol
      content in mitochondria and its association with oxidative stress in cultured
      hepatocytes and beta-cells were also examined. Results show that chronic exposure
      to glargine caused insulin resistance, hyperinsulinemia, and relative insulin
      deficiency (T2DM). Treatment with excess glargine led to loss of pancreatic
      islets, ectopic fat accumulation in liver, oxidative stress in liver and
      pancreas, and increased cholesterol content in mitochondria of liver and
      pancreas. Prolonged exposure of cultured primary hepatocytes and HIT-TI5 beta
      cells to insulin induced oxidative stress in a cholesterol synthesis-dependent
      manner. Together, our results show that chronic exposure to excess insulin can
      induce typical T2DM in normal mice fed on a chow diet. 

PMID- 24741075
TI  - SOMG-833, a novel selective c-MET inhibitor, blocks c-MET-dependent neoplastic
      effects and exerts antitumor activity.
AB  - The hepatocyte growth factor/c-MET signaling axis plays an important role in
      tumor cell proliferation, metastasis, and tumor angiogenesis, and therefore
      presents as an attractive target for cancer therapy. Notably, most small-molecule
      c-MET inhibitors currently undergoing clinical trials are multitarget inhibitors
      with the unwanted inhibition of additional kinases, often accounting for
      undesirable toxicity. Here, we discovered SOMG-833 [3-(4-methylpiperazin-1-yl)-5
      (3-nitrobenzylamino)-7-(trifluoromethyl) quinoline] as a potent and selective
      small-molecule c-MET inhibitor, with an average IC50 of 0.93 nM against c-MET,
      over 10,000-fold more potent compared with 19 tyrosine kinases, including c-MET
      family members and highly homologous kinases. SOMG-833 strongly suppressed c-MET
      mediated signaling transduction regardless of mechanistic complexity implicated
      in c-MET activation, including MET gene amplification, MET gene fusion, and HGF
      stimulated c-MET activation. In a panel of 24 human cancer or genetically
      engineered model cell lines, SOMG-833 potently inhibited c-MET-driven cell
      proliferation, whereas cancer cells lacking c-MET activation were markedly less
      sensitive (at least 15-fold) to the treatment. SOMG-833 also suppressed c-MET
      mediated migration, invasion, urokinase activity, and invasive growth phenotype.
      In addition, inhibition of primary human umbilical vascular endothelial cell
      (HUVEC) proliferation and downregulation of plasma proangiogenic factor
      interleukin-8 secretion resulted from SOMG-833 treatment, suggesting its
      significant antiangiogenic properties. Together, these results led to the
      remarkable antitumor efficacy of SOMG-833 in vivo, as demonstrated in c-MET
      dependent NIH-3T3/TPR-MET, U-87MG, and EBC-1 xenograft models. Collectively, our
      results suggested SOMG-833 as a promising candidate for highly selective c-MET
      inhibition and a powerful tool to investigate the sole role of MET kinase in
      cancer. 

PMID- 24741074
TI  - Inhibition of phosphatidylinositol 3-kinase/AKT signaling by NVP-BKM120 promotes
      ABT-737-induced toxicity in a caspase-dependent manner through mitochondrial
      dysfunction and DNA damage response in established and primary cultured
      glioblastoma cells.
AB  - Identification of therapeutic strategies that might enhance the efficacy of B
      cell lymphoma-2 (Bcl-2) inhibitor ABT-737 [N-{4-[4-(4-chloro-biphenyl-2-ylmethyl)
      piperazin-1-yl]-benzoyl}-4-(3-dimethylamino-1-phenylsulfanylmethyl-propylamino)-3
      nitro-benzenesulfonamide] is of great interest in many cancers, including glioma.
      Our recent study suggested that Akt is a crucial mediator of apoptosis
      sensitivity in response to ABT-737 in glioma cell lines. Inhibitors of
      phosphatidylinositol 3-kinase (PI3K)/Akt are currently being assessed clinically
      in patients with glioma. Because PI3K/Akt inhibition would be expected to have
      many proapoptotic effects, we hypothesized that there may be unique synergy
      between PI3K inhibitors and Bcl-2 homology 3 mimetics. Toward this end, we
      assessed the combination of the PI3K/Akt inhibitor NVP-BKM120 [5-(2,6
      dimorpholinopyrimidin-4-yl)-4-(trifluoromethyl)pyridin-2-amine] and the Bcl-2
      family inhibitor ABT-737 in established and primary cultured glioma cells. We
      found that the combined treatment with these agents led to a significant
      activation of caspase-8 and -3, PARP, and cell death, irrespective of PTEN
      status. The enhanced lethality observed with this combination also appears
      dependent on the loss of mitochondrial membrane potential and release of
      cytochrome c, smac/DIABLO, and apoptosis-inducing factor to the cytosol. Further
      study revealed that the upregulation of Noxa, truncation of Bid, and activation
      of Bax and Bak caused by these inhibitors were the key factors for the synergy.
      In addition, we demonstrated the release of proapoptotic proteins Bim and Bak
      from Mcl-1. We found defects in chromosome segregation leading to multinuclear
      cells and loss of colony-forming ability, suggesting the potential use of NVP
      BKM120 as a promising agent to improve the anticancer activities of ABT-737. 

PMID- 24741076
TI  - Ramipril protects the endothelium from high glucose-induced dysfunction through
      CaMKKbeta/AMPK and heme oxygenase-1 activation.
AB  - This study aims to investigate the effects of ramipril (RPL) on endothelial
      dysfunction associated with diabetes mellitus using cultured human aortic
      endothelial cells (HAECs) and a type 2 diabetic animal model. The effect of RPL
      on vasodilatory function in fat-fed, streptozotocin-treated rats was assessed.
      RPL treatment of 8 weeks alleviated insulin resistance and inhibited the decrease
      in endothelium-dependent vasodilation in diabetic rats. RPL treatment also
      reduced serum advanced glycation end products (AGE) concentration and rat aorta
      reactive oxygen species formation and increased aorta endothelium heme oxygenase
      1 (HO-1) expression. Exposure of HAECs to high concentrations of glucose induced
      prolonged oxidative stress, apoptosis, and accumulation of AGEs. These effects
      were abolished by incubation of ramiprilat (RPT), the active metabolite of RPL.
      However, treatment of HAECs with STO-609, a CaMKKbeta (Ca(2+)/calmodulin
      dependent protein kinase kinase-beta) inhibitor; compound C, an AMPK (AMP
      activated protein kinase) inhibitor; and Zn(II)PPIX, a selective HO-1 inhibitor,
      blocked these beneficial effects of RPT. In addition, RPT increased nuclear
      factor erythroid 2-related factor-2 (Nrf-2) nuclear translocation and activation
      in a CaMKKbeta/AMPK pathway-dependent manner, leading to increased expression of
      the Nrf-2-regulated antioxidant enzyme, HO-1. The inhibition of CaMKKbeta or AMPK
      by pharmaceutical approach ablated RPT-induced HO-1 expression. Taken together,
      RPL ameliorates insulin resistance and endothelial dysfunction in diabetes via
      reducing oxidative stress. These effects are mediated by RPL activation of CaMKK
      beta, which in turn activates the AMPK-Nrf-2-HO-1 pathway for enhanced
      endothelial function. 

PMID- 24741077
TI  - Expanded host diversity and geographic distribution of hantaviruses in sub
      Saharan Africa.
AB  - The recent discovery of hantaviruses in shrews and bats in West Africa suggests
      that other genetically distinct hantaviruses exist in East Africa. Genetic and
      phylogenetic analyses of newfound hantaviruses, detected in archival tissues from
      the Geata mouse shrew (Myosorex geata) and Kilimanjaro mouse shrew ( Myosorex
      zinki) captured in Tanzania, expands the host diversity and geographic
      distribution of hantaviruses and suggests that ancestral shrews and/or bats may
      have served as the original mammalian hosts of primordial hantaviruses. 

PMID- 24741078
TI  - Prolonged activity of the pestiviral RNase Erns as an interferon antagonist after
      uptake by clathrin-mediated endocytosis.
AB  - The RNase activity of the envelope glycoprotein E(rns) of the pestivirus bovine
      viral diarrhea virus (BVDV) is required to block type I interferon (IFN)
      synthesis induced by single-stranded RNA (ssRNA) and double-stranded RNA (dsRNA)
      in bovine cells. Due to the presence of an unusual membrane anchor at its C
      terminus, a significant portion of E(rns) is also secreted. In addition, a
      binding site for cell surface glycosaminoglycans is located within the C-terminal
      region of E(rns). Here, we show that the activity of soluble E(rns) as an IFN
      antagonist is not restricted to bovine cells. Extracellularly applied E(rns)
      protein bound to cell surface glycosaminoglycans and was internalized into the
      cells within 1 h of incubation by an energy-dependent mechanism that could be
      blocked by inhibitors of clathrin-dependent endocytosis. E(rns) mutants that
      lacked the C-terminal membrane anchor retained RNase activity but lost most of
      their intracellular activity as an IFN antagonist. Surprisingly, once taken up
      into the cells, E(rns) remained active and blocked dsRNA-induced IFN synthesis
      for several days. Thus, we propose that E(rns) acts as an enzymatically active
      decoy receptor that degrades extracellularly added viral RNA mainly in
      endolysosomal compartments that might otherwise activate intracellular pattern
      recognition receptors (PRRs) in order to maintain a state of innate
      immunotolerance. IMPORTANCE: The pestiviral RNase E(rns) was previously shown to
      inhibit viral ssRNA- and dsRNA-induced interferon (IFN) synthesis. However, the
      localization of E(rns) at or inside the cells, its species specificity, and its
      mechanism of interaction with cell membranes in order to block the host's innate
      immune response are still largely unknown. Here, we provide strong evidence that
      the pestiviral RNase E(rns) is taken up within minutes by clathrin-mediated
      endocytosis and that this uptake is mostly dependent on the glycosaminoglycan
      binding site located within the C-terminal end of the protein. Remarkably, the
      inhibitory activity of E(rns) remains for several days, indicating the very
      potent and prolonged effect of a viral IFN antagonist. This novel mechanism of an
      enzymatically active decoy receptor that degrades a major viral pathogen
      associated molecular pattern (PAMP) might be required to efficiently maintain
      innate and, thus, also adaptive immunotolerance, and it might well be relevant
      beyond the bovine species.

PMID- 24741079
TI  - Global genomic diversity of human papillomavirus 6 based on 724 isolates and 190
      complete genome sequences.
AB  - Human papillomavirus type 6 (HPV6) is the major etiological agent of anogenital
      warts and laryngeal papillomas and has been included in both the quadrivalent and
      nonavalent prophylactic HPV vaccines. This study investigated the global genomic
      diversity of HPV6, using 724 isolates and 190 complete genomes from six
      continents, and the association of HPV6 genomic variants with geographical
      location, anatomical site of infection/disease, and gender. Initially, a 2,800-bp
      E5a-E5b-L1-LCR fragment was sequenced from 492/530 (92.8%) HPV6-positive samples
      collected for this study. Among them, 130 exhibited at least one single
      nucleotide polymorphism (SNP), indel, or amino acid change in the E5a-E5b-L1-LCR
      fragment and were sequenced in full. A global alignment and maximum likelihood
      tree of 190 complete HPV6 genomes (130 fully sequenced in this study and 60
      obtained from sequence repositories) revealed two variant lineages, A and B, and
      five B sublineages: B1, B2, B3, B4, and B5. HPV6 (sub)lineage-specific SNPs and a
      960-bp representative region for whole-genome-based phylogenetic clustering
      within the L2 open reading frame were identified. Multivariate logistic
      regression analysis revealed that lineage B predominated globally. Sublineage B3
      was more common in Africa and North and South America, and lineage A was more
      common in Asia. Sublineages B1 and B3 were associated with anogenital infections,
      indicating a potential lesion-specific predilection of some HPV6 sublineages.
      Females had higher odds for infection with sublineage B3 than males. In
      conclusion, a global HPV6 phylogenetic analysis revealed the existence of two
      variant lineages and five sublineages, showing some degree of ethnogeographic,
      gender, and/or disease predilection in their distribution. IMPORTANCE: This study
      established the largest database of globally circulating HPV6 genomic variants
      and contributed a total of 130 new, complete HPV6 genome sequences to available
      sequence repositories. Two HPV6 variant lineages and five sublineages were
      identified and showed some degree of association with geographical location,
      anatomical site of infection/disease, and/or gender. We additionally identified
      several HPV6 lineage- and sublineage-specific SNPs to facilitate the
      identification of HPV6 variants and determined a representative region within the
      L2 gene that is suitable for HPV6 whole-genome-based phylogenetic analysis. This
      study complements and significantly expands the current knowledge of HPV6 genetic
      diversity and forms a comprehensive basis for future epidemiological,
      evolutionary, functional, pathogenicity, vaccination, and molecular assay
      development studies.

PMID- 24741080
TI  - Liquefaction of semen generates and later degrades a conserved semenogelin
      peptide that enhances HIV infection.
AB  - Semen enhances HIV infection in vitro, but how long it retains this activity has
      not been carefully examined. Immediately postejaculation, semen exists as a
      semisolid coagulum, which then converts to a more liquid form in a process termed
      liquefaction. We demonstrate that early during liquefaction, semen exhibits
      maximal HIV-enhancing activity that gradually declines upon further incubation.
      The decline in HIV-enhancing activity parallels the degradation of peptide
      fragments derived from the semenogelins (SEMs), the major components of the
      coagulum that are cleaved in a site-specific and progressive manner upon
      initiation of liquefaction. Because amyloid fibrils generated from SEM fragments
      were recently demonstrated to enhance HIV infection, we set out to determine
      whether any of the liquefaction-generated SEM fragments associate with the
      presence of HIV-enhancing activity. We identify SEM1 from amino acids 86 to 107
      [SEM1(86-107)] to be a short, cationic, amyloidogenic SEM peptide that is
      generated early in the process of liquefaction but that, conversely, is lost
      during prolonged liquefaction due to the activity of serine proteases. Synthetic
      SEM1(86-107) amyloids directly bind HIV-1 virions and are sufficient to enhance
      HIV infection of permissive cells. Furthermore, endogenous seminal levels of
      SEM1(86-107) correlate with donor-dependent variations in viral enhancement
      activity, and antibodies generated against SEM1(86-107) recognize endogenous
      amyloids in human semen. The amyloidogenic potential of SEM1(86-107) and its
      virus-enhancing properties are conserved among great apes, suggesting an
      evolutionarily conserved function. These studies identify SEM1(86-107) to be a
      key, HIV-enhancing amyloid species in human semen and underscore the dynamic
      nature of semen's HIV-enhancing activity. IMPORTANCE: Semen, the most common
      vehicle for HIV transmission, enhances HIV infection in vitro, but how long it
      retains this activity has not been investigated. Semen naturally undergoes
      physiological changes over time, whereby it converts from a gel-like consistency
      to a more liquid form. This process, termed liquefaction, is characterized at the
      molecular level by site-specific and progressive cleavage of SEMs, the major
      components of the coagulum, by seminal proteases. We demonstrate that the HIV
      enhancing activity of semen gradually decreases over the course of extended
      liquefaction and identify a naturally occurring semenogelin-derived fragment,
      SEM1(86-107), whose levels correlate with virus-enhancing activity over the
      course of liquefaction. SEM1(86-107) amyloids are naturally present in semen, and
      synthetic SEM1(86-107) fibrils bind virions and are sufficient to enhance HIV
      infection. Therefore, by characterizing dynamic changes in the HIV-enhancing
      activity of semen during extended liquefaction, we identified SEM1(86-107) to be
      a key virus-enhancing component of human semen.

PMID- 24741081
TI  - Chimeric GII.4 norovirus virus-like-particle-based vaccines induce broadly
      blocking immune responses.
AB  - There is currently no licensed vaccine for noroviruses, and development is
      hindered, in part, by an incomplete understanding of the host adaptive immune
      response to these highly heterogeneous viruses and rapid GII.4 norovirus
      molecular evolution. Emergence of a new predominant GII.4 norovirus strain occurs
      every 2 to 4 years. To address the problem of GII.4 antigenic variation, we
      tested the hypothesis that chimeric virus-like particle (VLP)-based vaccine
      platforms, which incorporate antigenic determinants from multiple strains into a
      single genetic background, will elicit a broader immune response against
      contemporary and emergent strains. Here, we compare the immune response generated
      by chimeric VLPs to that of parental strains and a multivalent VLP cocktail.
      Results demonstrate that chimeric VLPs induce a more broadly cross-blocking
      immune response than single parental VLPs and a similar response to a multivalent
      GII.4 VLP cocktail. Furthermore, we show that incorporating epitope site A alone
      from one strain into the background of another is sufficient to induce a blockade
      response against the strain donating epitope site A. This suggests a mechanism by
      which population-wide surveillance of mutations in a single epitope could be used
      to evaluate antigenic changes in order to identify potential emergent strains and
      quickly reformulate vaccines against future epidemic strains as they emerge in
      human populations. IMPORTANCE: Noroviruses are gastrointestinal pathogens that
      infect an estimated 21 million people per year in the United States alone. GII.4
      noroviruses account for >70% of all outbreaks, making them the most clinically
      important genotype. GII.4 noroviruses undergo a pattern of epochal evolution,
      resulting in the emergence of new strains with altered antigenicity over time,
      complicating vaccine design. This work is relevant to norovirus vaccine design as
      it demonstrates the potential for development of a chimeric VLP-based vaccine
      platform that may broaden the protective response against multiple GII.4 strains
      and proposes a potential reformulation strategy to control newly emergent strains
      in the human population.

PMID- 24741082
TI  - Phosphorylation of highly conserved serine residues in the influenza A virus
      nuclear export protein NEP plays a minor role in viral growth in human cells and
      mice.
AB  - Phosphorylation at the highly conserved serine residues S23 to S25 in the nuclear
      export protein (NEP) of influenza A viruses was suspected to regulate its nuclear
      export activity or polymerase activity-enhancing function. Mutation of these
      phosphoacceptor sites to either alanine or aspartic acid showed only a minor
      effect on both activities but revealed the presence of other phosphoacceptor
      sites that might be involved in regulating NEP activity. 

PMID- 24741083
TI  - Mechanism and significance of cell type-dependent neutralization of flaviviruses.
AB  - The production of neutralizing antibodies (NAbs) is a correlate of protection for
      many human vaccines, including currently licensed vaccines against flaviviruses.
      NAbs are typically measured using a plaque reduction neutralization test (PRNT).
      Despite its extensive use, parameters that impact the performance of the PRNT
      have not been investigated from a mechanistic perspective. The results of a
      recent phase IIb clinical trial of a tetravalent dengue virus (DENV) vaccine
      suggest that NAbs, as measured using a PRNT performed with Vero cells, do not
      correlate with protection. This surprising finding highlights the importance of
      understanding how well the PRNT captures the complexity of the NAb response to
      DENV. In this study, we demonstrated that the structural heterogeneity of
      flaviviruses arising from inefficient virion maturation impacts the results of
      neutralization assays in a cell type-dependent manner. Neutralization titers of
      several monoclonal antibodies were significantly reduced when assayed on Vero
      cells compared to Raji cells expressing DC-SIGNR. This pattern can be explained
      by differences in the efficiency with which partially mature flaviviruses attach
      to each cell type, rather than a differential capacity of antibody to block
      infection. Vero cells are poorly permissive to the fraction of virions that are
      most sensitive to neutralization. Analysis of sera from recipients of live
      attenuated monovalent DENV vaccine candidates revealed a strong correlation
      between the sensitivity of serum antibodies to the maturation state of DENV and
      cell type-dependent patterns of neutralization. Cross-reactive patterns of
      neutralization may be underrepresented by the "gold-standard" PRNT that employs
      Vero cells. IMPORTANCE: Cell type-dependent patterns of neutralization describe a
      differential capacity of antibodies to inhibit virus infection when assayed on
      multiple cellular substrates. In this study, we established a link between
      antibodies that neutralize infection in a cell type-dependent fashion and those
      sensitive to the maturation state of the flavivirus virion. We demonstrated that
      cell type-dependent neutralization reflects a differential capacity to measure
      neutralization of viruses that are incompletely mature. Partially mature virions
      that most efficiently bind maturation state-sensitive antibodies are poorly
      represented by assays typically used in support of flavivirus vaccine
      development. The selection of cellular substrate for neutralization assays may
      significantly impact evaluation of the neutralization potency of the polyclonal
      response. These data suggest that current assays do not adequately capture the
      full complexity of the neutralizing antibody response and may hinder the
      identification of correlates of protection following flavivirus vaccination.

PMID- 24741085
TI  - Determinants of Moloney murine leukemia virus Gag-Pol and genomic RNA
      proportions.
AB  - The Moloney murine leukemia virus (MoMLV) ribonucleoprotein complex is composed
      of an approximately 20:1 mixture of Gag and Gag-Pol polyproteins plus a single
      genomic RNA (gRNA) dimer. The mechanisms that regulate these proportions are
      unknown. Here, we examined whether virion proportions of Gag, Gag-Pol, and gRNA
      were determined by sampling (that is, if they reflected expression ratios or
      intracellular concentrations) or more specific recruitment. To this end, MoMLV
      Gag, Gag-Pol, and gRNA were expressed separately or together in various ratios.
      Varying the expression ratios of Gag and Gag-Pol revealed that Gag-Pol
      incorporation was stochastic and that the conserved 20:1 Gag/Gag-Pol ratio
      coincided with maximal particle production. When skewed expression ratios
      resulted in excess Gag-Pol, the released virions maintained the intracellular
      Gag/Gag-Pol ratios and the infectivity per virion was largely maintained, but
      virion production decreased sharply with high levels of Gag-Pol. The determinants
      of gRNA proportions were addressed by manipulating the amounts and contexts of
      functional nucleocapsid (NC) and the ratios of Gag to gRNA. The results showed
      that the NC domain of either Gag or Gag-Pol could provide gRNA packaging
      functions equally well. Unlike Gag-Pol, gRNA incorporation was saturable. An
      upper limit of gRNA incorporation was observed, and particle production was not
      disrupted by excess gRNA expression. These results indicate that the determinants
      of Gag/Gag-Pol proportions differ from those for Gag/gRNA. On the basis of the
      assumption that MoMLV evolved to produce virion components in optimal
      proportions, these data provide a means of estimating the proportion of unspliced
      MoMLV RNA that serves as genomic RNA. IMPORTANCE: Viruses assemble their progeny
      from within the cells that they parasitize, where they must sort through a rich
      milieu of host proteins and nucleic acids to gather together their own building
      blocks, which are also proteins and nucleic acids. The research described here
      addresses whether or not the proportions of viral proteins and nucleic acids that
      are brought together to form a retroviral particle are determined by random
      sampling from the cell-and thus dictated by the components' availabilities within
      the cell-or if the amounts of each molecule are specified by the virus
      replication process. The results indicated that protein components of the murine
      retrovirus studied here are recruited by chance but that a specific counting
      mechanism defines the amount of nucleic acid incorporated into each progeny
      virion.

PMID- 24741084
TI  - Small-molecule probes targeting the viral PPxY-host Nedd4 interface block egress
      of a broad range of RNA viruses.
AB  - Budding of filoviruses, arenaviruses, and rhabdoviruses is facilitated by
      subversion of host proteins, such as Nedd4 E3 ubiquitin ligase, by viral PPxY
      late (L) budding domains expressed within the matrix proteins of these RNA
      viruses. As L domains are important for budding and are highly conserved in a
      wide array of RNA viruses, they represent potential broad-spectrum targets for
      the development of antiviral drugs. To identify potential competitive blockers,
      we used the known Nedd4 WW domain-PPxY interaction interface as the basis of an
      in silico screen. Using PPxY-dependent budding of Marburg (MARV) VP40 virus-like
      particles (VLPs) as our model system, we identified small-molecule hit 1 that
      inhibited Nedd4-PPxY interaction and PPxY-dependent budding. This lead candidate
      was subsequently improved with additional structure-activity relationship (SAR)
      analog testing which enhanced antibudding activity into the nanomolar range.
      Current lead compounds 4 and 5 exhibit on-target effects by specifically blocking
      the MARV VP40 PPxY-host Nedd4 interaction and subsequent PPxY-dependent egress of
      MARV VP40 VLPs. In addition, lead compounds 4 and 5 exhibited antibudding
      activity against Ebola and Lassa fever VLPs, as well as vesicular stomatitis and
      rabies viruses (VSV and RABV, respectively). These data provide target validation
      and suggest that inhibition of the PPxY-Nedd4 interaction can serve as the basis
      for the development of a novel class of broad-spectrum, host-oriented antivirals
      targeting viruses that depend on a functional PPxY L domain for efficient egress.
      IMPORTANCE: There is an urgent and unmet need for the development of safe and
      effective therapeutics against biodefense and high-priority pathogens, including
      filoviruses (Ebola and Marburg) and arenaviruses (e.g., Lassa and Junin) which
      cause severe hemorrhagic fever syndromes with high mortality rates. We along with
      others have established that efficient budding of filoviruses, arenaviruses, and
      other viruses is critically dependent on the subversion of host proteins. As
      disruption of virus budding would prevent virus dissemination, identification of
      small-molecule compounds that block these critical viral-host interactions should
      effectively block disease progression and transmission. Our findings provide
      validation for targeting these virus-host interactions as we have identified lead
      inhibitors with broad-spectrum antiviral activity. In addition, such inhibitors
      might prove useful for newly emerging RNA viruses for which no therapeutics would
      be available.

PMID- 24741086
TI  - Cellular transcriptome analysis reveals differential expression of pro- and
      antiapoptosis genes by varicella-zoster virus-infected neurons and fibroblasts.
AB  - Transcriptional changes following varicella-zoster virus (VZV) infection of
      cultured human neurons derived from embryonic stem cells were compared to those
      in VZV-infected human foreskin fibroblasts. Transcription of 340 neuronal genes
      significantly altered by VZV infection included 223 transcript changes unique to
      neurons. Strikingly, genes inhibiting apoptosis were upregulated in neurons,
      while proapoptotic gene transcription was increased in fibroblasts. These data
      are a basis for discovery of differences in virus-host interactions between these
      VZV targets. 

PMID- 24741087
TI  - Lack of significant elevation of myeloid-derived suppressor cells in peripheral
      blood of chronically hepatitis C virus-infected individuals.
AB  - Myeloid-derived suppressor cells (MDSC) are immature myeloid cells with
      immunosuppressive function. Compared to the level in healthy controls (HC), no
      elevation of MDSC in chronic hepatitis C (cHEP-C) patients was found, and there
      was no difference in MDSC based on genotype or viral load (P > 0.25). Moreover,
      MDSC of cHEP-C patients inhibited CD8 T cell function as efficiently as MDSC of
      HC did. Since we detected neither quantitative nor qualitative differences in
      MDSC of cHEP-C patients relative to those of HC, we postulate that MDSC in
      peripheral blood are most likely not significant regarding immune dysfunction in
      cHEP-C. 

PMID- 24741088
TI  - Within-host whole-genome deep sequencing and diversity analysis of human
      respiratory syncytial virus infection reveals dynamics of genomic diversity in
      the absence and presence of immune pressure.
AB  - Human respiratory syncytial virus (RSV) is the leading cause of lower respiratory
      tract disease in infants and young children and an important respiratory pathogen
      in the elderly and immunocompromised. While population-wide molecular
      epidemiology studies have shown multiple cocirculating RSV genotypes and revealed
      antigenic and genetic change over successive seasons, little is known about the
      extent of viral diversity over the course of an individual infection, the origins
      of novel variants, or the effect of immune pressure on viral diversity and
      potential immune-escape mutations. To investigate viral population diversity in
      the presence and absence of selective immune pressures, we studied whole-genome
      deep sequencing of RSV in upper airway samples from an infant with severe
      combined immune deficiency syndrome and persistent RSV infection. The infection
      continued over several months before and after bone marrow transplant (BMT) from
      his RSV-immune father. RSV diversity was characterized in 26 samples obtained
      over 78 days. Diversity increased after engraftment, as defined by T-cell
      presence, and populations reflected variation mostly within the G protein, the
      major surface antigen. Minority populations with known palivizumab resistance
      mutations emerged after its administration. The viral population appeared to
      diversify in response to selective pressures, showing a statistically significant
      growth in diversity in the presence of pressure from immunity. Defining escape
      mutations and their dynamics will be useful in the design and application of
      novel therapeutics and vaccines. These data can contribute to future studies of
      the relationship between within-host and population-wide RSV phylodynamics.
      IMPORTANCE: Human RSV is an important cause of respiratory disease in infants,
      the elderly, and the immunocompromised. RSV circulating in a community appears to
      change season by season, but the amount of diversity generated during an
      individual infection and the impact of immunity on this viral diversity has been
      unclear. To address this question, we described within-host RSV diversity by
      whole-genome deep sequencing in a unique clinical case of an RSV-infected infant
      with severe combined immunodeficiency and effectively no adaptive immunity who
      then gained adaptive immunity after undergoing bone marrow transplantation. We
      found that viral diversity increased in the presence of adaptive immunity and was
      primarily within the G protein, the major surface antigen. These data will be
      useful in designing RSV treatments and vaccines and to help understand the
      relationship between the dynamics of viral diversification within individual
      hosts and the viral populations circulating in a community.

PMID- 24741089
TI  - Induction of Gag-specific CD4 T cell responses during acute HIV infection is
      associated with improved viral control.
AB  - Effector CD4 T cell responses have been shown to be critically involved in the
      containment and clearance of viral pathogens. However, their involvement in the
      pathogenesis of HIV infection is less clear, given their additional role as
      preferred viral targets. We previously demonstrated that the presence of HIV
      specific CD4 T cell responses is somewhat associated with HIV control and that
      specific CD4 T cell functions, such as direct cytolytic activity, can contribute
      to control of HIV viremia. However, little is known about how the induction of
      HIV-specific CD4 T cell responses during acute HIV infection influences disease
      progression and whether responses induced during the early phase of infection are
      preferentially depleted. We therefore longitudinally assessed, in a cohort of 55
      acutely HIV-infected individuals, HIV-specific CD4 T cell responses from acute to
      chronic infection. Interestingly, we found that the breadth, magnitude, and
      protein dominance of HIV-specific CD4 T cell responses remained remarkably stable
      over time. Moreover, we found that the epitopes targeted at a high frequency in
      acute HIV infection were recognized at the same frequency by HIV-specific CD4 T
      cells in chronic HIV infection. Interestingly the induction of Gag-specific CD4 T
      cell responses in acute HIV infection was significantly inversely correlated with
      viral set point in chronic HIV infection (R = -0.5; P = 0.03), while the
      cumulative contribution of Env-specific CD4 T cell responses showed the reverse
      effect. Moreover, individuals with HIV-specific CD4 T cell responses dominantly
      targeting Gag over Env in acute HIV infection remained off antiretroviral therapy
      significantly longer (P = 0.03; log rank). Thus, our data suggest that the
      induction of HIV-specific CD4 T cell responses during acute HIV infection is
      beneficial overall and does not fuel disease progression. IMPORTANCE: CD4 T cells
      are critical for the clearance and control of viral infections. However, HIV
      preferentially infects HIV-specific CD4 T cells. Thus, their contribution to the
      control of HIV viremia is uncertain. Here, we study HIV-specific CD4 T cell
      responses from acute to chronic HIV infection and show that the generation of
      certain CD4 responses is associated with control rather than disease progression.

PMID- 24741090
TI  - Kaposi's sarcoma-associated herpesvirus-encoded LANA interacts with host KAP1 to
      facilitate establishment of viral latency.
AB  - Kaposi's sarcoma-associated herpesvirus (KSHV) typically displays two different
      phases in its life cycle, the default latent phase and the lytic phase. There is
      a short period of lytic gene expression in the early stage of KSHV primary
      infection. The factors involved in the shutdown process of lytic gene expression
      are poorly identified. It has been shown that the latency-associated nuclear
      antigen (LANA) encoded by KSHV plays an important role in the establishment of
      viral latency. In screening, we identified a host protein, Kruppel-associated box
      domain-associated protein 1 (KAP1), that bound to LANA. We validated the
      interaction between LANA and KAP1 in vivo and in vitro, as well as their
      colocalization in the nucleus. We mapped out that LANA interacted with both the N
      and C-terminal domains of KAP1. Based on the interface of LANA-KAP1 interaction
      determined, we proved that LANA recruited KAP1 to the RTA promoter region of the
      KSHV genome. We revealed that KAP1 was involved in transcriptional repression by
      LANA. We found multiple cooccupation sites of LANA and KAP1 on the whole KSHV
      genome by chromatin immunoprecipitation for sequencing (ChIP-seq) and
      demonstrated that LANA-recruited KAP1 played a critical role in the shutdown of
      lytic gene expression during the early stage of KSHV primary infection. Taken
      together, our data suggest that LANA interacts with KAP1 and represses lytic gene
      expression to facilitate the establishment of KSHV latency. IMPORTANCE: Our study
      revealed the mechanism of transcriptional repression by LANA during KSHV primary
      infection, providing new insights into the process of KSHV latency establishment.

PMID- 24741091
TI  - Analysis of Lujo virus cell entry using pseudotype vesicular stomatitis virus.
AB  - Several arenaviruses are known to cause viral hemorrhagic fever (VHF) in sub
      Saharan Africa and South America, where VHF is a major public health and medical
      concern. The biosafety level 4 categorization of these arenaviruses restricts
      their use and has impeded biological studies, including therapeutic drug and/or
      vaccine development. Due to difficulties associated with handling live viruses,
      pseudotype viruses, which transiently bear arenavirus envelope proteins based on
      vesicular stomatitis virus (VSV) or retrovirus, have been developed as surrogate
      virus systems. Here, we report the development of a pseudotype VSV bearing each
      envelope protein of various species of arenaviruses (AREpv), including the newly
      identified Lujo virus (LUJV) and Chapare virus. Pseudotype arenaviruses generated
      in 293T cells exhibited high infectivity in various mammalian cell lines. The
      infections by New World and Old World AREpv were dependent on their receptors
      (human transferrin receptor 1 [hTfR1] and alpha-dystroglycan [alphaDG],
      respectively). However, infection by pseudotype VSV bearing the LUJV envelope
      protein (LUJpv) occurred independently of hTfR1 and alphaDG, indicating that
      LUJpv utilizes an unidentified receptor. The pH-dependent endocytosis of AREpv
      was confirmed by the use of lysosomotropic agents. The fusion of cells expressing
      these envelope proteins, except for those expressing the LUJV envelope protein,
      was induced by transient treatment at low pH values. LUJpv infectivity was
      inhibited by U18666A, a cholesterol transport inhibitor. Furthermore, the
      infectivity of LUJpv was significantly decreased in the Niemann-Pick C1 (NPC1)
      deficient cell line, suggesting the necessity for NPC1 activity for efficient
      LUJpv infection. IMPORTANCE: LUJV is a newly identified arenavirus associated
      with a VHF outbreak in southern Africa. Although cell entry for many arenaviruses
      has been studied, cell entry for LUJV has not been characterized. In this study,
      we found that LUJpv utilizes neither alphaDG nor hTfR1 as a receptor and found
      unique characteristics of LUJV glycoprotein in membrane fusion and cell entry.
      Proper exclusion of cholesterol or some kinds of lipids may play important roles
      in LUJpv cell entry.

PMID- 24741092
TI  - Evolution of puma lentivirus in bobcats (Lynx rufus) and mountain lions (Puma
      concolor) in North America.
AB  - Mountain lions (Puma concolor) throughout North and South America are infected
      with puma lentivirus clade B (PLVB). A second, highly divergent lentiviral clade,
      PLVA, infects mountain lions in southern California and Florida. Bobcats (Lynx
      rufus) in these two geographic regions are also infected with PLVA, and to date,
      this is the only strain of lentivirus identified in bobcats. We sequenced full
      length PLV genomes in order to characterize the molecular evolution of PLV in
      bobcats and mountain lions. Low sequence homology (88% average pairwise identity)
      and frequent recombination (1 recombination breakpoint per 3 isolates analyzed)
      were observed in both clades. Viral proteins have markedly different patterns of
      evolution; sequence homology and negative selection were highest in Gag and Pol
      and lowest in Vif and Env. A total of 1.7% of sites across the PLV genome evolve
      under positive selection, indicating that host-imposed selection pressure is an
      important force shaping PLV evolution. PLVA strains are highly spatially
      structured, reflecting the population dynamics of their primary host, the bobcat.
      In contrast, the phylogeography of PLVB reflects the highly mobile mountain lion,
      with diverse PLVB isolates cocirculating in some areas and genetically related
      viruses being present in populations separated by thousands of kilometers. We
      conclude that PLVA and PLVB are two different viral species with distinct feline
      hosts and evolutionary histories. Importance: An understanding of viral evolution
      in natural host populations is a fundamental goal of virology, molecular biology,
      and disease ecology. Here we provide a detailed analysis of puma lentivirus (PLV)
      evolution in two natural carnivore hosts, the bobcat and mountain lion. Our
      results illustrate that PLV evolution is a dynamic process that results from high
      rates of viral mutation/recombination and host-imposed selection pressure.

PMID- 24741093
TI  - Herpes simplex virus protein kinases US3 and UL13 modulate VP11/12
      phosphorylation, virion packaging, and phosphatidylinositol 3-kinase/Akt
      signaling activity.
AB  - The phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway plays key roles in
      diverse cellular activities and promotes cell growth and survival. It is
      therefore unsurprising that most viruses modify this pathway in order to
      facilitate their replication and spread. Previous work has suggested that the
      herpes simplex virus 1 (HSV-1) tegument proteins VP11/12 and US3 protein kinase
      modulate the PI3K/Akt pathway, albeit in opposing ways: VP11/12 binds and
      activates Src family kinases (SFKs), is tyrosine phosphorylated, recruits PI3K in
      an SFK-dependent fashion, and is required for HSV-induced phosphorylation of Akt
      on its activating residues; in contrast, US3 inhibits Akt activation and directly
      phosphorylates downstream Akt targets. We examined if US3 negatively regulates
      Akt by dampening the signaling activity of VP11/12. Consistent with this
      hypothesis, the enhanced Akt activation that occurs during US3-null infection
      requires VP11/12 and correlates with an increase in SFK-dependent VP11/12
      tyrosine phosphorylation. In addition, deleting US3 leads to a striking increase
      in the relative abundances of several VP11/12 species that migrate with reduced
      mobility during SDS-PAGE. These forms arise through phosphorylation, strictly
      require the viral UL13 protein kinase, and are excluded from virions. Taken in
      combination, these data indicate that US3 dampens SFK-dependent tyrosine and UL13
      dependent serine/threonine phosphorylation of VP11/12, thereby inhibiting VP11/12
      signaling and promoting virion packaging of VP11/12. These results illustrate
      that protein phosphorylation events mediated by viral protein kinases serve to
      coordinate the roles of VP11/12 as a virion component and intracellular signaling
      molecule. IMPORTANCE: Herpesvirus tegument proteins play dual roles during the
      viral life cycle, serving both as structural components of the virus particle and
      as modulators of cellular and viral functions in infected cells. How these two
      roles are coordinated during infection and virion assembly is a fundamental and
      largely unanswered question. Here we addressed this issue with herpes simplex
      virus VP11/12, a tegument protein that activates the cellular PI3K/Akt signaling
      pathway. We showed that protein phosphorylation mediated by the viral US3 and
      UL13 kinases serves to orchestrate its functions: UL13 appears to inhibit VP11/12
      virion packaging, while US3 antagonizes UL13 action and independently dampens
      VP11/12 signaling activity.

PMID- 24741094
TI  - CTCF binding to the first intron of the major immediate early (MIE) gene of human
      cytomegalovirus (HCMV) negatively regulates MIE gene expression and HCMV
      replication.
AB  - Human cytomegalovirus (HCMV) gene expression during infection is highly
      regulated, with sequential expression of immediate-early (IE), early (E), and
      late (L) gene transcripts. To explore the potential role of chromatin regulatory
      factors that may regulate HCMV gene expression and DNA replication, we
      investigated the interaction of HCMV with the cellular chromatin-organizing
      factor CTCF. Here, we show that HCMV-infected cells produce higher levels of CTCF
      mRNA and protein at early stages of infection. We also show that CTCF depletion
      by short hairpin RNA results in an increase in major IE (MIE) and E gene
      expression and an about 50-fold increase in HCMV particle production. We
      identified a DNA sequence (TTAACGGTGGAGGGCAGTGT) in the first intron (intron A)
      of the MIE gene that interacts directly with CTCF. Deletion of this CTCF-binding
      site led to an increase in MIE gene expression in both transient-transfection and
      infection assays. Deletion of the CTCF-binding site in the HCMV bacterial
      artificial chromosome plasmid genome resulted in an about 10-fold increase in the
      rate of viral replication relative to either wild-type or revertant HCMV. The
      CTCF-binding site deletion had no detectable effect on MIE gene-splicing
      regulation, nor did CTCF knockdown or overexpression of CTCF alter the ratio of
      IE1 to IE2. Therefore, CTCF binds to DNA within the MIE gene at the position of
      the first intron to affect RNA polymerase II function during the early stages of
      viral transcription. Finally, the CTCF-binding sequence in CMV is evolutionarily
      conserved, as a similar sequence in murine CMV (MCMV) intron A was found to
      interact with CTCF and similarly function in the repression of MCMV MIE gene
      expression mediated by CTCF. IMPORTANCE: Our findings that CTCF binds to intron A
      of the cytomegalovirus (CMV) major immediate-early (MIE) gene and functions to
      repress MIE gene expression and viral replication are highly significant. For the
      first time, a chromatin-organizing factor, CTCF, has been found to facilitate
      human CMV gene expression, which affects viral replication. We also identified a
      CTCF-binding motif in the first intron (also called intron A) that directly binds
      to CTCF and is required for CTCF to repress MIE gene expression. Finally, we show
      that the CTCF-binding motif is conserved in CMV because a similar DNA sequence
      was found in murine CMV (MCMV) that is required for CTCF to bind to MCMV MIE gene
      to repress MCMV MIE gene expression.

PMID- 24741095
TI  - Kaposi's sarcoma-associated herpesvirus-encoded LANA can induce chromosomal
      instability through targeted degradation of the mitotic checkpoint kinase Bub1.
AB  - Kaposi's sarcoma-associated herpesvirus (KSHV) has a significant contributory
      role in the development of three major human neoplastic or lymphoproliferative
      diseases: Kaposi's sarcoma (KS), primary effusion lymphoma (PEL), and
      multicentric Castleman's disease (MCD). These diseases are associated with
      chromosomal instability, a hallmark of human cancer. The latency-associated
      nuclear antigen (LANA) encoded by KSHV plays a key role in regulating a number of
      cellular pathways critical for oncogenesis. KSHV LANA alone can induce the
      development of B-cell hyperplasia and lymphoma in mice expressing LANA. LANA also
      induces chromosomal instability, thus promoting oncogenesis. However, the precise
      mechanism underlying LANA-mediated chromosomal instability remains uncharted.
      Here we report that LANA promoted the induction of chromosomal instability and
      the formation of micronuclei and multinucleation through its interaction with one
      of the critical spindle checkpoint proteins, Bub1, and the resulting degradation
      of Bub1. This interaction occurs through the Knl and kinase domains of Bub1,
      identified as important for stability and degradation. These results suggest that
      LANA can dysregulate Bub1 activity, which leads to aberrant chromosome
      replication and aneuploidy, thus contributing to KSHV-mediated oncogenesis.
      IMPORTANCE: This work represents the first set of results identifying a novel
      mechanism by which LANA, a latency-associated antigen encoded by KSHV, can induce
      the degradation of Bub1, a spindle checkpoint protein that is important for
      spindle checkpoint signaling and chromosome segregation. The downregulation of
      Bub1 mediated by LANA resulted in chromosomal instability, a hallmark of cancer.
      We further investigated the specific domains of Bub1 that are required for the
      interaction between LANA and Bub1. The results demonstrated that the Knl and
      kinase domains of Bub1 are required for the interaction between LANA and Bub1. In
      addition, we also investigated the mechanism by which LANA promoted Bub1
      degradation. Our results showed that LANA interacted physically with the anaphase
      promoting complex (APC/C), thus promoting the degradation of Bub1 in a ubiquitin
      dependent process.

PMID- 24741096
TI  - Hepatitis delta antigen requires a flexible quasi-double-stranded RNA structure
      to bind and condense hepatitis delta virus RNA in a ribonucleoprotein complex.
AB  - The circular genome and antigenome RNAs of hepatitis delta virus (HDV) form
      characteristic unbranched, quasi-double-stranded RNA secondary structures in
      which short double-stranded helical segments are interspersed with internal loops
      and bulges. The ribonucleoprotein complexes (RNPs) formed by these RNAs with the
      virus-encoded protein hepatitis delta antigen (HDAg) perform essential roles in
      the viral life cycle, including viral replication and virion formation. Little is
      understood about the formation and structure of these complexes and how they
      function in these key processes. Here, the specific RNA features required for
      HDAg binding and the topology of the complexes formed were investigated.
      Selective 2'OH acylation analyzed by primer extension (SHAPE) applied to free and
      HDAg-bound HDV RNAs indicated that the characteristic secondary structure of the
      RNA is preserved when bound to HDAg. Notably, the analysis indicated that
      predicted unpaired positions in the RNA remained dynamic in the RNP. Analysis of
      the in vitro binding activity of RNAs in which internal loops and bulges were
      mutated and of synthetically designed RNAs demonstrated that the distinctive
      secondary structure, not the primary RNA sequence, is the major determinant of
      HDAg RNA binding specificity. Atomic force microscopy analysis of RNPs formed in
      vitro revealed complexes in which the HDV RNA is substantially condensed by
      bending or wrapping. Our results support a model in which the internal loops and
      bulges in HDV RNA contribute flexibility to the quasi-double-stranded structure
      that allows RNA bending and condensing by HDAg. IMPORTANCE: RNA-protein complexes
      (RNPs) formed by the hepatitis delta virus RNAs and protein, HDAg, perform
      critical roles in virus replication. Neither the structures of these RNPs nor the
      RNA features required to form them have been characterized. HDV RNA is unusual in
      that it forms an unbranched quasi-double-stranded structure in which short base
      paired segments are interspersed with internal loops and bulges. We analyzed the
      role of the HDV RNA sequence and secondary structure in the formation of a
      minimal RNP and visualized the structure of this RNP using atomic force
      microscopy. Our results indicate that HDAg does not recognize the primary
      sequence of the RNA; rather, the principle contribution of unpaired bases in HDV
      RNA to HDAg binding is to allow flexibility in the unbranched quasi-double
      stranded RNA structure. Visualization of RNPs by atomic force microscopy
      indicated that the RNA is significantly bent or condensed in the complex.

PMID- 24741097
TI  - Vaginal myeloid dendritic cells transmit founder HIV-1.
AB  - We report that primary human vaginal dendritic cells (DCs) display a myeloid
      phenotype and express CD4, CCR5, and CXCR4. Vaginal CD13(+) CD11c(+) DCs rapidly
      and efficiently bound transmitted/founder (T/F) CCR5-tropic (R5) viruses,
      transported them through explanted vaginal mucosa, and transmitted them in trans
      to vaginal and blood lymphocytes. Vaginal myeloid DCs may play a key role in
      capturing and disseminating T/F R5 HIV-1 in vivo and are candidate "gatekeeper"
      cells in HIV-1 transmission. 

PMID- 24741099
TI  - Intrahost dynamics of influenza virus reassortment.
AB  - The segmented nature of the influenza virus genome allows reassortment between
      coinfecting viruses. This process of genetic exchange vastly increases the
      diversity of circulating influenza viruses. The importance of reassortment to
      public health is clear from its role in the emergence of a number of
      epidemiologically important viruses, including novel pandemic and epidemic
      strains. To gauge its impact on within-host genomic variation, we tracked
      reassortment in coinfected guinea pigs over time and given matched or discordant
      doses of coinfecting viruses. To ensure unbiased detection of reassortants, we
      used parental viruses of equivalent fitness that differ only by noncoding
      nucleotide changes. These viruses were based on the isolate A/Panama/2007/1999
      (H3N2). At a dose of 2 * 10(2) PFU, one parental virus was absent from each
      guinea pig throughout the time course, indicating the presence of a bottleneck.
      With an intermediate dose of 2 * 10(3) PFU, genomic diversity present in nasal
      lavage samples increased from 1 to 3 days postinfection (dpi) and then declined
      by 6 dpi. With a high dose of 2 * 10(6) PFU, however, reassortment levels were
      high (avg. 59%) at 1 dpi and remained stable. Even late in the course of
      infection, parental viruses were not eclipsed by reassortants, suggesting that a
      uniformly high multiplicity of infection was not achieved in vivo. Inoculation
      with ~10-fold discordant doses did not reduce reassortment relative to equivalent
      inputs but markedly changed the spectrum of genotypes produced. Our data reveal
      the potential for reassortment to contribute to intrahost diversity in mixed
      influenza virus infection. IMPORTANCE: Influenza virus reassortment is prevalent
      in nature and is a major contributor to the diversity of influenza viruses
      circulating in avian, swine, human and other host species. This diversity, in
      turn, increases the potential for influenza viruses to evade selective pressures
      or adapt to new host environments. As examples, reassortment was key to the
      emergence of the 1957, 1968, and 2009 pandemics; the unusually severe influenza
      epidemics of 2003, 1951, and 1947; and the rise in adamantane resistance among
      currently circulating human H3N2 viruses. We reveal here the diversity of viral
      genotypes generated over time in a host coinfected with two influenza viruses. We
      found that intrahost diversity driven by reassortment is dynamic and dependent on
      the amount of each virus initiating infection. Our results demonstrate the
      readiness with which reassortant influenza viruses arise, offering new insight
      into this important mechanism of influenza virus evolution.

PMID- 24741098
TI  - Vaccination with Gag, Vif, and Nef gene fragments affords partial control of
      viral replication after mucosal challenge with SIVmac239.
AB  - Broadly targeted cellular immune responses are thought to be important for
      controlling replication of human and simian immunodeficiency viruses (HIV and
      SIV). However, eliciting such responses by vaccination is complicated by
      immunodominance, the preferential targeting of only a few of the many possible
      epitopes of a given antigen. This phenomenon may be due to the coexpression of
      dominant and subdominant epitopes by the same antigen-presenting cell and may be
      overcome by distributing these sequences among several different vaccine
      constructs. Accordingly, we tested whether vaccinating rhesus macaques with
      "minigenes" encoding fragments of Gag, Vif, and Nef resulted in broadened
      cellular responses capable of controlling SIV replication. We delivered these
      minigenes through combinations of recombinant Mycobacterium bovis BCG (rBCG),
      electroporated recombinant DNA (rDNA) along with an interleukin-12 (IL-12)
      expressing plasmid (EP rDNA plus pIL-12), yellow fever vaccine virus 17D
      (rYF17D), and recombinant adenovirus serotype 5 (rAd5). Although priming with EP
      rDNA plus pIL-12 increased the breadth of vaccine-induced T-cell responses, this
      effect was likely due to the improved antigen delivery afforded by
      electroporation rather than modulation of immunodominance. Indeed, Mamu-A*01(+)
      vaccinees mounted CD8(+) T cells directed against only one subdominant epitope,
      regardless of the vaccination regimen. After challenge with SIVmac239, vaccine
      efficacy was limited to a modest reduction in set point in some of the groups and
      did not correlate with standard T-cell measurements. These findings suggest that
      broad T-cell responses elicited by conventional vectors may not be sufficient to
      substantially contain AIDS virus replication. IMPORTANCE: Immunodominance poses a
      major obstacle to the generation of broadly targeted, HIV-specific cellular
      responses by vaccination. Here we attempted to circumvent this phenomenon and
      thereby broaden the repertoire of SIV-specific cellular responses by vaccinating
      rhesus macaques with minigenes encoding fragments of Gag, Vif, and Nef. In
      contrast to previous mouse studies, this strategy appeared to minimally affect
      monkey CD8(+) T-cell immundominance hierarchies, as seen by the detection of only
      one subdominant epitope in Mamu-A*01(+) vaccinees. This finding underscores the
      difficulty of inducing subdominant CD8(+) T cells by vaccination and demonstrates
      that strategies other than gene fragmentation may be required to significantly
      alter immunodominance in primates. Although some of the regimens tested here were
      extremely immunogenic, vaccine efficacy was limited to a modest reduction in set
      point viremia after challenge with SIVmac239. No correlates of protection were
      identified. These results reinforce the notion that vaccine immunogenicity does
      not predict control of AIDS virus replication.

PMID- 24741100
TI  - Role of herpes simplex virus 1 immediate early protein ICP22 in viral nuclear
      egress.
AB  - In order to investigate the novel function(s) of the herpes simplex virus 1 (HSV
      1) immediate early protein ICP22, we screened for ICP22-binding proteins in HSV-1
      infected cells. Our results were as follows. (i) Tandem affinity purification of
      ICP22 from infected cells, coupled with mass spectrometry-based proteomics and
      subsequent analyses, demonstrates that ICP22 forms a complex(es) with the HSV-1
      proteins UL31, UL34, UL47 (or VP13/14), and/or Us3. All these proteins were
      previously reported to be important for viral egress through the nuclear
      membrane. (ii) ICP22 colocalizes with UL31 and UL34 at the nuclear membrane in
      wild-type HSV-1-infected cells. (iii) The UL31-null mutation prevents the
      targeting of ICP22 to the nuclear membrane. (iv) The ICP22-null mutation resulted
      in UL31 and UL34 being mislocalized in the endoplasmic reticulum (in addition to
      the nuclear membrane) and significantly reduced numbers of primary enveloped
      virions in the perinuclear space, although capsids accumulated in the nuclei.
      Collectively, these results suggest that (i) ICP22 interacts with HSV-1
      regulators of nuclear egress, including UL31, UL34, UL47, and Us3 in HSV-1
      infected cells; (ii) UL31 mediates the recruitment and anchorage of ICP22 at the
      nuclear membrane; and (iii) ICP22 plays a regulatory role in HSV-1 primary
      envelopment, probably by interacting with and regulating UL31 and UL34. Here we
      report a previously unknown function for ICP22 in the regulation of HSV-1 nuclear
      egress. IMPORTANCE: The herpes simplex virus 1 (HSV-1) immediate early protein
      ICP22 is recognized primarily as a regulator of viral gene expression. In this
      study, we show that ICP22 interacts with the HSV-1 proteins UL31 and UL34, which
      play crucial roles at the nuclear membrane in HSV-1 primary envelopment during
      viral nuclear egress. We also demonstrate that UL31 is required for the targeting
      of ICP22 to the nuclear membrane and that ICP22 is required for the correct
      localization of UL31 and/or UL34. Furthermore, we confirm that ICP22 is required
      for efficient HSV-1 primary envelopment during viral nuclear egress. Thus, we
      report, for the first time, that ICP22 plays a regulatory role in HSV-1 nuclear
      egress.

PMID- 24741101
TI  - Anti-inflammatory cytokines directly inhibit innate but not adaptive CD8+ T cell
      functions.
AB  - Virus-specific CD8(+) T cells provide classical adaptive immunity by responding
      to cognate peptide antigen, but they may also act in an "innate" capacity by
      responding directly to cytokine stimulation. Here, we examined regulation of
      these distinct T cell functions by anti-inflammatory cytokines (interleukin-4 [IL
      4], IL-10, and transforming growth factor beta [TGF-beta]). Innate gamma
      interferon (IFN-gamma) production by CD8(+) T cells following exposure to IL-12
      plus IL-18, IL-12 plus tumor necrosis factor alpha (TNF-alpha), or IL-12 plus IL
      15 was inhibited by exposure to anti-inflammatory cytokines either before or
      shortly after stimulation. However, inhibition was not universal, as other
      activation parameters, including upregulation of CD25 and CD69, remained largely
      unaltered. In contrast, peptide-specific T cell responses were resistant to
      inhibition by anti-inflammatory cytokines. This was not due to downregulation of
      cytokine receptor expression or an inability to signal through cytokine receptors
      since phosphorylation of STAT proteins remained intact. These results highlight
      key differences in cytokine-mediated regulation of innate and adaptive T cell
      functions, which may help balance effective antiviral immune responses while
      reducing T cell-mediated immunopathology. IMPORTANCE: This study demonstrates key
      differences between the regulation of "innate" and "adaptive" CD8(+) T cell
      functions following activation by innate cytokines or viral peptide. Innate
      production of IFN-gamma by CD8(+) T cells following exposure to IL-12 plus IL-18,
      IL-12 plus TNF-alpha, or IL-12 plus IL-15 was inhibited by exposure to anti
      inflammatory cytokines (IL-4, IL-10, and TGF-beta). However, inhibition was not
      universal, as other activation parameters, including upregulation of CD25 and
      CD69, remained largely unaltered. In contrast, peptide-specific T cell responses
      were resistant to inhibition by anti-inflammatory cytokines. This distinct
      regulation of innate and adaptive T cell functions may serve to reduce T cell
      mediated immunopathology while still allowing for effective antiviral responses
      at a site of infection.

PMID- 24741102
TI  - Characterization of the nucleocytoplasmic shuttle of the matrix protein of
      influenza B virus.
AB  - Influenza B virus is an enveloped negative-strand RNA virus that contributes
      considerably to annual influenza illnesses in human. The matrix protein of
      influenza B virus (BM1) acts as a cytoplasmic-nuclear shuttling protein during
      the early and late stages of infection. The mechanism of this intracellular
      transport of BM1 was revealed through the identification of two leucine-rich CRM1
      dependent nuclear export signals (NESs) (3 to 14 amino acids [aa] and 124 to 133
      aa), one bipartite nuclear localization signal (NLS) (76 to 94 aa), and two
      phosphorylation sites (80T and 84S) in BM1. The biological function of the NLS
      and NES regions were determined through the observation of the intracellular
      distribution of enhanced green fluorescent protein (EGFP)-tagged signal peptides,
      and wild-type, NES-mutant, and NLS-mutant EGFP-BM1. Furthermore, the NLS
      phosphorylation sites 80T and 84S, were found to be required for the nuclear
      accumulation of EGFP-NLS and for the efficient binding of EGFP-BM1 to human
      importin-alpha1. Moreover, all of these regions/sites were required for the
      generation of viable influenza B virus in a 12-plasmid virus rescue system.
      IMPORTANCE: This study expands our understanding of the life cycle of influenza B
      virus by defining the dynamic mechanism of the nucleocytoplasmic shuttle of BM1
      and could provide a scientific basis for the development of antiviral medication.

PMID- 24741103
TI  - Interspecies differences in virus uptake versus cardiac function of the
      coxsackievirus and adenovirus receptor.
AB  - The coxsackievirus and adenovirus receptor (CAR) is a cell contact protein with
      an important role in virus uptake. Its extracellular immunoglobulin domains
      mediate the binding to coxsackievirus and adenovirus as well as homophilic and
      heterophilic interactions between cells. The cytoplasmic tail links CAR to the
      cytoskeleton and intracellular signaling cascades. In the heart, CAR is crucial
      for embryonic development, electrophysiology, and coxsackievirus B infection.
      Noncardiac functions are less well understood, in part due to the lack of
      suitable animal models. Here, we generated a transgenic mouse that rescued the
      otherwise embryonic-lethal CAR knockout (KO) phenotype by expressing chicken CAR
      exclusively in the heart. Using this rescue model, we addressed interspecies
      differences in coxsackievirus uptake and noncardiac functions of CAR. Survival of
      the noncardiac CAR KO (ncKO) mouse indicates an essential role for CAR in the
      developing heart but not in other tissues. In adult animals, cardiac activity was
      normal, suggesting that chicken CAR can replace the physiological functions of
      mouse CAR in the cardiomyocyte. However, chicken CAR did not mediate virus entry
      in vivo, so that hearts expressing chicken instead of mouse CAR were protected
      from infection and myocarditis. Comparison of sequence homology and modeling of
      the D1 domain indicate differences between mammalian and chicken CAR that relate
      to the sites important for virus binding but not those involved in
      homodimerization. Thus, CAR-directed anticoxsackievirus therapy with only minor
      adverse effects in noncardiac tissue could be further improved by selectively
      targeting the virus-host interaction while maintaining cardiac function.
      IMPORTANCE: Coxsackievirus B3 (CVB3) is one of the most common human pathogens
      causing myocarditis. Its receptor, the coxsackievirus and adenovirus receptor
      (CAR), not only mediates virus uptake but also relates to cytoskeletal
      organization and intracellular signaling. Animals without CAR die prenatally with
      major cardiac malformations. In the adult heart, CAR is important for virus entry
      and electrical conduction, but its nonmuscle functions are largely unknown. Here,
      we show that chicken CAR expression exclusively in the heart can rescue the
      otherwise embryonic-lethal CAR knockout phenotype but does not support CVB3
      infection of adult cardiomyocytes. Our findings have implications for the
      evolution of virus-host versus physiological interactions involving CAR and could
      help to improve future coxsackievirus-directed therapies inhibiting virus
      replication while maintaining CAR's cellular functions.

PMID- 24741104
TI  - Enhanced viral replication and modulated innate immune responses in infant airway
      epithelium following H1N1 infection.
AB  - Influenza is the cause of significant morbidity and mortality in pediatric
      populations. The contribution of pulmonary host defense mechanisms to viral
      respiratory infection susceptibility in very young children is poorly understood.
      As a surrogate to compare mucosal immune responses of infant and adult lungs,
      rhesus monkey primary airway epithelial cell cultures were infected with pandemic
      influenza A/H1N1 virus in vitro. Virus replication, cytokine secretion, cell
      viability, and type I interferon (IFN) pathway PCR array profiles were evaluated
      for both infant and adult cultures. In comparison with adult cultures, infant
      cultures showed significantly increased levels of H1N1 replication, reduced alpha
      interferon (IFN-alpha) protein synthesis, and no difference in cell death
      following infection. Age-dependent differences in expression levels of multiple
      genes associated with the type I IFN pathway were observed in H1N1-infected
      cultures. To investigate the pulmonary and systemic responses to H1N1 infection
      in early life, infant monkeys were inoculated with H1N1 by upper airway
      administration. Animals were monitored for virus and parameters of inflammation
      over a 14-day period. High H1N1 titers were recovered from airways at day 1, with
      viral RNA remaining detectable until day 9 postinfection. Despite viral
      clearance, bronchiolitis and alveolitis persisted at day 14 postinfection;
      histopathological analysis revealed alveolar septal thickening and intermittent
      type II pneumocyte hyperplasia. Our overall findings are consistent with the
      known susceptibility of pediatric populations to respiratory virus infection and
      suggest that intrinsic developmental differences in airway epithelial cell immune
      function may contribute to the limited efficacy of host defense during early
      childhood. IMPORTANCE: To the best of our knowledge, this study represents the
      first report of intrinsic developmental differences in infant airway epithelial
      cells that may contribute to the increased susceptibility of the host to
      respiratory virus infections. Despite the global burden of influenza, there are
      currently no vaccine formulations approved for children <6 months of age. Given
      the challenges of conducting experimental studies involving pediatric patients,
      rhesus monkeys are an ideal laboratory animal model to investigate the maturation
      of pulmonary mucosal immune mechanisms during early life because they are most
      similar to those of humans with regard to postnatal maturation of the lung
      structure and the immune system. Thus, our findings are highly relevant to
      translational medicine, and these data may ultimately lead to novel approaches
      that enhance airway immunity in very young children.

PMID- 24741105
TI  - Characteristics of nucleocytoplasmic transport of H1N1 influenza A virus nuclear
      export protein.
AB  - The influenza A virus nuclear export protein (NEP) plays crucial roles in the
      nuclear export of the viral ribonucleoprotein complex through the chromosome
      region maintenance 1 (CRM1)-mediated cellular protein transport system. However,
      the detailed mechanism of NEP nucleocytoplasmic trafficking remains incompletely
      understood. Here, we investigated the subcellular localization of NEP from two
      strains of H1N1 influenza A virus and found that 2009 swine-origin H1N1 influenza
      A virus A/California/04/2009 (CA04) NEP displayed a distinct cellular
      distribution pattern, forming unique nuclear aggregates, compared to A/WSN/33
      (H1N1) (WSN) NEP. Characterization of the nucleocytoplasmic transport pathways of
      these two NEPs showed that they both enter the nucleus by passive diffusion but
      are exported through the nuclear export receptor CRM1-mediated pathway with
      different efficiencies. The two identified nuclear export signals (NESs) on the
      two NEPs functioned similarly despite differences in their amino acid sequences.
      Using a two-hybrid assay, we confirmed that the CA04 NEP interacts less
      efficiently with CRM1 and that a threonine residue at position 48 is responsible
      for the nuclear aggregation. The present study revealed the dissimilarity in
      subcellular NEP transport processes between the 2009 pandemic (H1N1) influenza A
      virus CA04 and the laboratory-adapted H1N1 virus WSN and uncovered the mechanism
      responsible for this difference. IMPORTANCE: Because the efficiency of the
      nucleocytoplasmic transport of viral components is often correlated with the
      viral RNA polymerase activity, propagation, and host range of influenza viruses,
      the present study investigated the subcellular localization of NEP from two
      strains of H1N1 influenza virus. We found that the NEPs of both
      A/California/04/2009 (H1N1) (CA04) and A/WSN/33 (H1N1) (WSN) enter the nucleus by
      passive diffusion but are exported with different efficiencies, which were caused
      by weaker binding activity between the CA04 NEP and CRM1. The results of the
      present study revealed characteristics of the nuclear import and export pathways
      of NEP and the mechanism responsible for the differences in the cellular
      distribution of NEP between two H1N1 strains.

PMID- 24741106
TI  - Type I interferon signals in macrophages and dendritic cells control dengue virus
      infection: implications for a new mouse model to test dengue vaccines.
AB  - Dengue virus (DENV) infects an estimated 400 million people every year, causing
      prolonged morbidity and sometimes mortality. Development of an effective vaccine
      has been hampered by the lack of appropriate small animal models; mice are
      naturally not susceptible to DENV and only become infected if highly
      immunocompromised. Mouse models lacking both type I and type II interferon (IFN)
      receptors (AG129 mice) or the type I IFN receptor (IFNAR(-/-) mice) are
      susceptible to infection with mouse-adapted DENV strains but are severely
      impaired in mounting functional immune responses to the virus and thus are of
      limited use for study. Here we used conditional deletion of the type I IFN
      receptor (IFNAR) on individual immune cell subtypes to generate a minimally
      manipulated mouse model that is susceptible to DENV while retaining global immune
      competence. Mice lacking IFNAR expression on CD11c(+) dendritic cells and LysM(+)
      macrophages succumbed completely to DENV infection, while mice deficient in the
      receptor on either CD11c(+) or LysM(+) cells were susceptible to infection but
      often resolved viremia and recovered fully from infection. Conditional IFNAR mice
      responded with a swift and strong CD8(+) T-cell response to viral infection,
      compared to a weak response in IFNAR(-/-) mice. Furthermore, mice lacking IFNAR
      on either CD11c(+) or LysM(+) cells were also sufficiently immunocompetent to
      raise a protective immune response to a candidate subunit vaccine against DENV-2.
      These data demonstrate that mice with conditional deficiencies in expression of
      the IFNAR represent improved models for the study of DENV immunology and
      screening of vaccine candidates. IMPORTANCE: Dengue virus infects 400 million
      people every year worldwide, causing 100 million clinically apparent infections,
      which can be fatal if untreated. Despite many years of research, there are no
      effective vaccine and no antiviral treatment available for dengue. Development of
      vaccines has been hampered in particular by the lack of a suitable small animal
      model. Mouse models used to test dengue vaccine are deficient in interferon (IFN)
      type I signaling and severely immunocompromised and therefore likely not ideal
      for the testing of vaccines. In this study, we explored alternative models
      lacking the IFN receptor only on certain cell types. We show that mice lacking
      the IFN receptor on either CD11c- or LysM-expressing cells (conditional IFNAR
      mice) are susceptible to dengue virus infection. Importantly, we demonstrate that
      conditional IFN receptor knockout mice generate a better immune response to live
      virus and a candidate dengue vaccine compared to IFNAR mice and are resistant to
      subsequent challenge.

PMID- 24741107
TI  - NS2 proteins of GB virus B and hepatitis C virus share common protease activities
      and membrane topologies.
AB  - GB virus B (GBV-B), which is hepatotropic in experimentally infected small New
      World primates, is a member of the Hepacivirus genus but phylogenetically
      relatively distant from hepatitis C virus (HCV). To gain insights into the role
      and specificity of hepaciviral nonstructural protein 2 (NS2), which is required
      for HCV polyprotein processing and particle morphogenesis, we investigated
      whether NS2 structural and functional features are conserved between HCV and GBV
      B. We found that GBV-B NS2, like HCV NS2, has cysteine protease activity
      responsible for cleavage at the NS2/NS3 junction, and we experimentally confirmed
      the location of this junction within the viral polyprotein. A model for GBV-B NS2
      membrane topology was experimentally established by determining the membrane
      association properties of NS2 segments fused to green fluorescent protein (GFP)
      and their nuclear magnetic resonance structures using synthetic peptides as well
      as by applying an N-glycosylation scanning approach. Similar glycosylation
      studies confirmed the HCV NS2 organization. Together, our data show that despite
      limited amino acid sequence similarity, GBV-B and HCV NS2 proteins share a
      membrane topology with 3 N-terminal transmembrane segments, which is also
      predicted to apply to other recently discovered hepaciviruses. Based on these
      data and using trans-complementation systems, we found that intragenotypic hybrid
      NS2 proteins with heterologous N-terminal membrane segments were able to
      efficiently trans-complement an assembly-deficient HCV mutant with a point
      mutation in the NS2 C-terminal domain, while GBV-B/HCV or intergenotypic NS2
      chimeras were not. These studies indicate that virus- and genotype-specific
      intramolecular interactions between N- and C-terminal domains of NS2 are
      critically involved in HCV morphogenesis. IMPORTANCE: Nonstructural protein 2
      (NS2) of hepatitis C virus (HCV) is a multifunctional protein critically involved
      in polyprotein processing and virion morphogenesis. To gain insights into NS2
      mechanisms of action, we investigated whether NS2 structural and functional
      features are conserved between HCV and GB virus B (GBV-B), a phylogenetically
      relatively distant primate hepacivirus. We showed that GBV-B NS2, like HCV NS2,
      carries cysteine protease activity. We experimentally established a model for GBV
      B NS2 membrane topology and demonstrated that despite limited sequence
      similarity, GBV-B and HCV NS2 share an organization with three N-terminal
      transmembrane segments. We found that the role of HCV NS2 in particle assembly is
      genotype specific and relies on critical interactions between its N- and C
      terminal domains. This first comparative analysis of NS2 proteins from two
      hepaciviruses and our structural predictions of NS2 from other newly identified
      mammal hepaciviruses highlight conserved key features of the hepaciviral life
      cycle.

PMID- 24741108
TI  - Cyclic nucleotide-gated channels, calmodulin, adenylyl cyclase, and
      calcium/calmodulin-dependent protein kinase II are required for late, but not
      early, long-term memory formation in the honeybee.
AB  - Memory is a dynamic process that allows encoding, storage, and retrieval of
      information acquired through individual experience. In the honeybee Apis
      mellifera, olfactory conditioning of the proboscis extension response (PER) has
      shown that besides short-term memory (STM) and mid-term memory (MTM), two phases
      of long-term memory (LTM) are formed upon multiple-trial conditioning: an early
      phase (e-LTM) which depends on translation from already available mRNA, and a
      late phase (l-LTM) which requires de novo transcription and translation. Here we
      combined olfactory PER conditioning and neuropharmacological inhibition and
      studied the involvement of the NO-cGMP pathway, and of specific molecules, such
      as cyclic nucleotide-gated channels (CNG), calmodulin (CaM), adenylyl cyclase
      (AC), and Ca(2+)/calmodulin-dependent protein kinase (CaMKII), in the formation
      of olfactory LTM in bees. We show that in addition to NO-cGMP and cAMP-PKA, CNG
      channels, CaM, AC, and CaMKII also participate in the formation of a l-LTM (72-h
      post-conditioning) that is specific for the learned odor. Importantly, the same
      molecules are dispensable for olfactory learning and for the formation of both
      MTM (in the minute and hour range) and e-LTM (24-h post-conditioning), thus
      suggesting that the signaling pathways leading to l-LTM or e-LTM involve
      different molecular actors. 

PMID- 24741109
TI  - A specific role for hippocampal mossy fiber's zinc in rapid storage of emotional
      memories.
AB  - We investigated the specific role of zinc present in large amounts in the
      synaptic vesicles of mossy fibers and coreleased with glutamate in the CA3
      region. In previous studies, we have shown that blockade of zinc after release
      has no effect on the consolidation of spatial learning, while zinc is required
      for the consolidation of contextual fear conditioning. Although both are
      hippocampo-dependent processes, fear conditioning to the context implies a strong
      emotional burden. To verify the hypothesis that zinc could play a specific role
      in enabling sustainable memorization of a single event with a strong emotional
      component, we used a neuropharmacological approach combining a glutamate receptor
      antagonist with different zinc chelators. Results show that zinc is mandatory to
      allow the consolidation of one-shot memory, thus being the key element allowing
      the hippocampus submitted to a strong emotional charge to switch from the
      cognitive mode to a flashbulb memory mode. Individual differences in learning
      abilities have been known for a long time to be totally or partially compensated
      by distributed learning practice. Here we show that contextual fear conditioning
      impairments due to zinc blockade can be efficiently reduced by distributed
      learning practice. 

PMID- 24741110
TI  - The eIF2alpha kinase PERK limits the expression of hippocampal metabotropic
      glutamate receptor-dependent long-term depression.
AB  - The proper regulation of translation is required for the expression of long
      lasting synaptic plasticity. A major site of translational control involves the
      phosphorylation of eukaryotic initiation factor 2 alpha (eIF2alpha) by PKR-like
      endoplasmic reticulum (ER) kinase (PERK). To determine the role of PERK in
      hippocampal synaptic plasticity, we used the Cre-lox expression system to
      selectively disrupt PERK expression in the adult mouse forebrain. Here, we
      demonstrate that in hippocampal area CA1, metabotropic glutamate receptor (mGluR)
      dependent long-term depression (LTD) is associated with increased eIF2alpha
      phosphorylation, whereas stimulation of early- and late-phase long-term
      potentiation (E-LTP and L-LTP, respectively) is associated with decreased
      eIF2alpha phosphorylation. Interesting, although PERK-deficient mice exhibit
      exaggerated mGluR-LTD, both E-LTP and L-LTP remained intact. We also found that
      mGluR-LTD is associated with a PERK-dependent increase in eIF2alpha
      phosphorylation. Our findings are consistent with the notion that eIF2alpha
      phosphorylation is a key site for the bidirectional control of persistent forms
      of synaptic LTP and LTD and suggest a distinct role for PERK in mGluR-LTD. 

PMID- 24741111
TI  - Regulation dynamics of Leishmania differentiation: deconvoluting signals and
      identifying phosphorylation trends.
AB  - Leishmania are obligatory intracellular parasitic protozoa that cause a wide
      range of diseases in humans, cycling between extracellular promastigotes in the
      mid-gut of sand flies and intracellular amastigotes in the phagolysosomes of
      mammalian macrophages. Although many of the molecular mechanisms of development
      inside macrophages remain a mystery, the development of a host-free system that
      simulates phagolysosome conditions (37  degrees C and pH 5.5) has provided new
      insights into these processes. The time course of promastigote-to-amastigote
      differentiation can be divided into four morphologically distinct phases: I,
      signal perception (0-5 h after exposure); II, movement cessation and aggregation
      (5-10 h); III, amastigote morphogenesis (10-24 h); and IV, maturation (24-120 h).
      Transcriptomic and proteomic analyses have indicated that differentiation is a
      coordinated process that results in adaptation to life inside phagolysosomes.
      Recent phosphoproteomic analysis revealed extensive differences in
      phosphorylation between promastigotes and amastigotes and identified stage
      specific phosphorylation motifs. We hypothesized that the differentiation signal
      activates a phosphorylation pathway that initiates Leishmania transformation, and
      here we used isobaric tags for relative and absolute quantitation to interrogate
      the dynamics of changes in the phosphorylation profile during Leishmania donovani
      promastigote-to-amastigote differentiation. Analysis of 163 phosphopeptides (from
      106 proteins) revealed six distinct kinetic profiles; with increases in
      phosphorylation predominated during phases I and III, whereas phases II and IV
      were characterized by greater dephosphorylation. Several proteins (including a
      protein kinase) were phosphorylated in phase I after exposure to the complete
      differentiation signal (i.e. signal-specific; 37  degrees C and pH 5.5), but not
      after either of the physical parameters separately. Several other protein kinases
      (including regulatory subunits) and phosphatases also showed changes in
      phosphorylation during differentiation. This work constitutes the first genome
      scale interrogation of phosphorylation dynamics in a parasitic protozoa,
      revealing the outline of a signaling pathway during Leishmania differentiation.
      The mass spectrometry proteomics data have been deposited to the ProteomeXchange
      Consortium (identifier PXD000671). Data can be viewed using ProteinPilotTM
      software. 

PMID- 24741112
TI  - StableIsotope Labeling with Amino Acids in Cell Culture (SILAC)-based strategy
      for proteome-wide thermodynamic analysis of protein-ligand binding interactions.
AB  - Described here is a quantitative mass spectrometry-based proteomics method for
      the large-scale thermodynamic analysis of protein-ligand binding interactions.
      The methodology utilizes a chemical modification strategy termed, Stability of
      Proteins from Rates of Oxidation (SPROX), in combination with a Stable Isotope
      Labeling with Amino Acids in Cell Culture (SILAC) approach to compare the
      equilibrium folding/unfolding properties of proteins in the absence and presence
      of target ligands. The method, which is general with respect to ligand, measures
      the ligand-induced changes in protein stability associated with protein-ligand
      binding. The methodology is demonstrated in a proof-of-principle study in which
      the well-characterized protein-drug interaction between cyclosporine A (CsA) and
      cyclophilin A was successfully analyzed in the context of a yeast cell lysate. A
      control experiment was also performed to assess the method's false positive rate
      of ligand discovery, which was found to be on the order of 0.4 - 3.5%. The new
      method was utilized to characterize the adenosine triphosphate (ATP)-interactome
      in Saccharomyces cerevisiae using the nonhydrolyzable ATP analog, adenylyl
      imidodiphosphate (AMP-PNP), and the proteins in a yeast cell lysate. The new
      methodology enabled the interrogation of 526 yeast proteins for interactions with
      ATP using 2035 peptide probes. Ultimately, 325 peptide hits from 139 different
      proteins were identified. Approximately 70% of the hit proteins identified in
      this work were not previously annotated as ATP binding proteins. However, nearly
      two-thirds of the newly discovered ATP interacting proteins have known
      interactions with other nucleotides and co-factors (e.g. NAD and GTP), DNA, and
      RNA based on GO-term analyses. The current work is the first proteome-wide
      profile of the yeast ATP-interactome, and it is the largest proteome-wide profile
      of any ATP-interactome generated, to date, using an energetics-based method. The
      data is available via ProteomeXchange with identifiers PXD000858, DOI
      10.6019/PXD000858, and PXD000860. 

PMID- 24741113
TI  - Large scale analysis of co-existing post-translational modifications in histone
      tails reveals global fine structure of cross-talk.
AB  - Mass spectrometry (MS) is a powerful analytical method for the identification and
      quantification of co-existing post-translational modifications in histone
      proteins. One of the most important challenges in current chromatin biology is to
      characterize the relationships between co-existing histone marks, the order and
      hierarchy of their deposition, and their distinct biological functions. We
      developed the database CrossTalkDB to organize observed and reported co-existing
      histone marks as revealed by MS experiments of histone proteins and their derived
      peptides. Statistical assessment revealed sample-specific patterns for the co
      frequency of histone post-translational modifications. We implemented a new
      method to identify positive and negative interplay between pairs of methylation
      and acetylation marks in proteins. Many of the detected features were conserved
      between different cell types or exist across species, thereby revealing general
      rules for cross-talk between histone marks. The observed features are in
      accordance with previously reported examples of cross-talk. We observed novel
      types of interplay among acetylated residues, revealing positive cross-talk
      between nearby acetylated sites but negative cross-talk for distant ones, and for
      discrete methylation states at Lys-9, Lys-27, and Lys-36 of histone H3,
      suggesting a more differentiated functional role of methylation beyond the
      general expectation of enhanced activity at higher methylation states. 

PMID- 24741114
TI  - Glycoproteomic analysis of prostate cancer tissues by SWATH mass spectrometry
      discovers N-acylethanolamine acid amidase and protein tyrosine kinase 7 as
      signatures for tumor aggressiveness.
AB  - The identification of biomarkers indicating the level of aggressiveness of
      prostate cancer (PCa) will address the urgent clinical need to minimize the
      general overtreatment of patients with non-aggressive PCa, who account for the
      majority of PCa cases. Here, we isolated formerly N-linked glycopeptides from
      normal prostate (n = 10) and from non-aggressive (n = 24), aggressive (n = 16),
      and metastatic (n = 25) PCa tumor tissues and analyzed the samples using SWATH
      mass spectrometry, an emerging data-independent acquisition method that generates
      a single file containing fragment ion spectra of all ionized species of a sample.
      The resulting datasets were searched using a targeted data analysis strategy in
      which an a priori spectral reference library representing known N-glycosites of
      the human proteome was used to identify groups of signals in the SWATH mass
      spectrometry data. On average we identified 1430 N-glycosites from each sample.
      Out of those, 220 glycoproteins showed significant quantitative changes
      associated with diverse biological processes involved in PCa aggressiveness and
      metastasis and indicated functional relationships. Two glycoproteins, N
      acylethanolamine acid amidase and protein tyrosine kinase 7, that were
      significantly associated with aggressive PCa in the initial sample cohort were
      further validated in an independent set of patient tissues using tissue
      microarray analysis. The results suggest that N-acylethanolamine acid amidase and
      protein tyrosine kinase 7 may be used as potential tissue biomarkers to avoid
      overtreatment of non-aggressive PCa. 

PMID- 24741115
TI  - Proteomic analysis of intact flagella of procyclic Trypanosoma brucei cells
      identifies novel flagellar proteins with unique sub-localization and dynamics.
AB  - Cilia and flagella are complex organelles made of hundreds of proteins of highly
      variable structures and functions. Here we report the purification of intact
      flagella from the procyclic stage of Trypanosoma brucei using mechanical
      shearing. Structural preservation was confirmed by transmission electron
      microscopy that showed that flagella still contained typical elements such as the
      membrane, the axoneme, the paraflagellar rod, and the intraflagellar transport
      particles. It also revealed that flagella severed below the basal body, and were
      not contaminated by other cytoskeletal structures such as the flagellar pocket
      collar or the adhesion zone filament. Mass spectrometry analysis identified a
      total of 751 proteins with high confidence, including 88% of known flagellar
      components. Comparison with the cell debris fraction revealed that more than half
      of the flagellum markers were enriched in flagella and this enrichment criterion
      was taken into account to identify 212 proteins not previously reported to be
      associated to flagella. Nine of these were experimentally validated including a
      14-3-3 protein not yet reported to be associated to flagella and eight novel
      proteins termed FLAM (FLAgellar Member). Remarkably, they localized to five
      different subdomains of the flagellum. For example, FLAM6 is restricted to the
      proximal half of the axoneme, no matter its length. In contrast, FLAM8 is
      progressively accumulating at the distal tip of growing flagella and half of it
      still needs to be added after cell division. A combination of RNA interference
      and Fluorescence Recovery After Photobleaching approaches demonstrated very
      different dynamics from one protein to the other, but also according to the stage
      of construction and the age of the flagellum. Structural proteins are added to
      the distal tip of the elongating flagellum and exhibit slow turnover whereas
      membrane proteins such as the arginine kinase show rapid turnover without a
      detectible polarity. 

PMID- 24741116
TI  - Proteomic analysis of altered extracellular matrix turnover in bleomycin-induced
      pulmonary fibrosis.
AB  - Fibrotic disease is characterized by the pathological accumulation of
      extracellular matrix (ECM) proteins. Surprisingly, very little is known about the
      synthesis and degradation rates of the many proteins and proteoglycans that
      constitute healthy or pathological extracellular matrix. A comprehensive
      understanding of altered ECM protein synthesis and degradation during the onset
      and progression of fibrotic disease would be immensely valuable. We have
      developed a dynamic proteomics platform that quantifies the fractional synthesis
      rates of large numbers of proteins via stable isotope labeling and LC/MS-based
      mass isotopomer analysis. Here, we present the first broad analysis of ECM
      protein kinetics during the onset of experimental pulmonary fibrosis. Mice were
      labeled with heavy water for up to 21 days following the induction of lung
      fibrosis with bleomycin. Lung tissue was subjected to sequential protein
      extraction to fractionate cellular, guanidine-soluble ECM proteins and residual
      insoluble ECM proteins. Fractional synthesis rates were calculated for 34 ECM
      proteins or protein subunits, including collagens, proteoglycans, and
      microfibrillar proteins. Overall, fractional synthesis rates of guanidine-soluble
      ECM proteins were faster than those of insoluble ECM proteins, suggesting that
      the insoluble fraction reflected older, more mature matrix components. This was
      confirmed through the quantitation of pyridinoline cross-links in each protein
      fraction. In fibrotic lung tissue, there was a significant increase in the
      fractional synthesis of unique sets of matrix proteins during early (pre-1 week)
      and late (post-1 week) fibrotic response. Furthermore, we isolated fast turnover
      subpopulations of several ECM proteins (e.g. type I collagen) based on guanidine
      solubility, allowing for accelerated detection of increased synthesis of
      typically slow-turnover protein populations. This establishes the presence of
      multiple kinetic pools of pulmonary collagen in vivo with altered turnover rates
      during evolving fibrosis. These data demonstrate the utility of dynamic
      proteomics in analyzing changes in ECM protein turnover associated with the onset
      and progression of fibrotic disease. 

PMID- 24741117
TI  - THE EDUCATION-HEALTH GRADIENT.
AB  - In this paper, we determine the role played by early cognitive, noncognitive, and
      health endowments. We identify the causal effect of education on health and
      health-related behaviors. We develop an empirical model of schooling choice and
      post-schooling outcomes, where both schooling and the outcomes determined in part
      by schooling are influenced by measured early family environments and latent
      capabilities (cognitive, noncognitive and health). We show that family background
      characteristics, and cognitive, noncognitive, and health endowments developed by
      age 10, are important determinants of labor market and health disparities at age
      30. Not properly accounting for personality traits overestimates the importance
      of cognitive ability in determining adult health. Selection on factors determined
      early in life explains more than half of the observed difference by education in
      poor health, depression, and obesity. Education has an important causal effect in
      explaining differences in many adult outcomes and healthy behaviors. We uncover
      significant gender differences. We go beyond the current literature which
      typically estimates mean effects to compute distributions of treatment effects.
      We show how the health returns to education can vary among individuals who are
      similar with respect to their observed characteristics, and how a mean effect can
      hide gains and losses for different individuals. Our research highlights the
      important role played by the early years in producing health.

PMID- 24741118
TI  - S1-Guideline on Bacterial Vaginosis in Gynecology and Obstetrics: Long version -
      AWMF Guideline, registration no. 015/028, July 2013 Langfassung - AWMF-Register
      Nr. 015/028, Juli 2013.

PMID- 24741120
TI  - The Effects of Suburethral Tape on the Symptoms of Overactive Bladder.
AB  - Suburethral tension-free vaginal tape is used for the treatment of stress urinary
      incontinence with a high success rate. Often patients report having stress
      incontinence, as well as co-existing micturition problems which are attributable
      to overactive bladder syndrome (OAB). The present study examines the effect of
      suburethral tape on the symptoms of OAB. In the study, we used the transobturator
      vaginal tape inside-out technique (TVT-O). Materials and Methods: 53 patients
      were included in the study, all had proven urodynamic stress incontinence and
      symptoms of overactive bladder. The patients were examined preoperatively and 3
      months after the TVT-O placement. Results: The individual OAB symptoms improved
      significantly, with urinary frequency and urge incontinence improving more than
      nocturia. The frequency of micturition decreased on average from 16.1 to 10.1
      episodes/24 hours, while nocturnal frequency of micturition decreased from 2.2 to
      1.1. Not a single patient experienced the simultaneous worsening of all three
      measured variables, however 19 % of patients did report their simultaneous
      disappearance. Their quality of life that had been affected by OAB was measured
      on the basis of validated questionnaires, and found to have improved
      significantly. Only 28 % of patients reported a desire for drug treatment of OAB
      symptoms following tape placement. Conclusions: TVT-O placement leads to a
      significant improvement of the symptoms of overactive bladder syndrome. Patient
      quality of life - which was affected by OAB - was also enhanced by the tape
      placement. This accounts for a substantial share of the overall success of the
      suburethral tape.

PMID- 24741119
TI  - Indications for Cardiopulmonary Bypass During Pregnancy and Impact on Fetal
      Outcomes.
AB  - Background: Cardiac operations in pregnant patients are a challenge for
      physicians in multidisciplinary teams due to the complexity of the condition
      which affects both mother and baby. Management strategies vary on a case-by-case
      basis. Feto-neonatal and maternal outcomes after cardiopulmonary bypass (CPB) in
      pregnancy, especially long-term follow-up results, have not been sufficiently
      described. Methods: This review was based on a complete literature retrieval of
      articles published between 1991 and April 30, 2013. Results: Indications for CPB
      during pregnancy were cardiac surgery in 150 (96.8 %) patients, most of which
      consisted of valve replacements for mitral and/or aortic valve disorders,
      resuscitation due to amniotic fluid embolism, autotransfusion, and circulatory
      support during cesarean section to improve patient survival in 5 (3.2 %)
      patients. During CPB, fetuses showed either a brief heart rate drop with natural
      recovery after surgery or, in most cases, fetal heart rate remained normal
      throughout the whole course of CPB. Overall feto-neonatal mortality was 18.6 %.
      In comparison with pregnant patients whose baby survived, feto-neonatal death
      occurred after a significantly shorter gestational period at the time of onset of
      cardiac symptoms, cardiac surgery/resuscitation under CPB in the whole patient
      setting, or cardiac surgery/resuscitation with CPB prior to delivery.
      Conclusions: The most common surgical indications for CPB during pregnancy were
      cardiac surgery, followed by resuscitation for cardiopulmonary collapse. CPB was
      used most frequently in maternal cardiac surgery/resuscitation in the second
      trimester. Improved CPB conditions including high flow, high pressure and
      normothermia or mild hypothermia during pregnancy have benefited maternal and
      feto-neonatal outcomes. A shorter gestational period and the use of CPB during
      pregnancy were closely associated with feto-neonatal mortality. It is therefore
      important to attempt delivery ahead of surgery/CPB or to defer surgery till late
      pregnancy.

PMID- 24741121
TI  - Impact of Retropubic vs. Transobturator Slings for Urinary Incontinence on
      Myofascial Structures of the Pelvic Floor, Adductor and Abdominal Muscles.
AB  - Suburethral tension-free slings (tapes or bands) are an essential component in
      the operative treatment of urinary incontinence. In the present contribution the
      influence of the type of suburethral sling (retropubic vs. transobturator) on the
      myofascial structures of the abdominal, adductor and pelvic floor muscles is
      examined. For this purpose, 70 patients were prospectively observed clinically
      and physiotherapeutically. Significant differences were seen in the improvement
      of the pelvic floor musculature (strength, endurance, speed) after placement of a
      suburethral sling, irrespective of whether it was of the retropubic or the
      transobturator type. Thus, after surgical treatment patients should be encouraged
      to undertake further pelvic floor exercising or this should be prescribed for
      them. There were no significant changes in the abdominal and adductor muscles but
      there were slight increases with regard to pain level, pain on palpation, and
      trigger points after placement of both types of sling; thus this is not a
      criterion in the decision as to which type of sling to use.

PMID- 24741122
TI  - Natural Size Development of Myomata - Ultrasound Observational Study of 55
      Premenopausal Patients.
AB  - Objective: The natural growth progression of uterine leiomyomata will be studied
      and used to identify potential predictive criteria of myoma size development.
      This should answer the question of whether myoma growth is dependent on patient
      age, or on the localisation or original size of the myoma, as well as how much of
      a size increase can be expected per unit of time, and the proportion of myomata
      which shrink. Patients and Methods: Patient files of a myoma surgery from 2010 to
      2012 were retrospectively evaluated. The following inclusion criteria applied:
      diagnosis of at least one, but not more than three myomata, a minimum of two
      consultations within three years, the performance of a transvaginal ultrasound to
      determine size, no pregnancy, and no medical or surgical myoma reduction
      measures. Only premenopausal patients were included in the analysis. Myoma volume
      was approximated using a formula similar to that used to calculate the volume of
      an ellipsoid. Results: 55 out of 102 patients (median age: 38 years), in which a
      total of 72 myomata were diagnosed, could be included in the evaluation. The
      median diameter of the myomata at the start of the study was 3.8 cm, with an
      average growth rate of 30 % over 6 months (range: - 46 to + 459 %). 15 % of the
      myomata regressed. The linear regression analysis showed a correlation between
      myoma growth over 6 months, the original size of the myoma (p = 0.023) and
      patient age (p = 0.038), but no connection was found to the localisation of the
      myoma. Smaller myomata decreased significantly more in size than larger myomata
      (p = 0.011). Older patients presented with larger myomata. Conclusions: Myomata
      demonstrate a strikingly large variation in size development. Their growth is
      highly individual and not ultimately predictable. Patients should be advised of
      the possibility of spontaneous myoma regression.

PMID- 24741123
TI  - Treatment of Iron Deficiency with or without Anaemia with Intravenous Ferric
      Carboxymaltose in Gynaecological Practices - A Non-Interventional Study.
AB  - In this multi-centre, prospective, non-interventional study, the effectiveness
      and tolerance of ferric carboxymaltose (ferinject(r); FCM) was tested through use
      in standard gynaecological practice. In total, data from 273 patients was
      evaluated. 193 of these patients displayed iron deficiency anaemia (IDA), and 68
      had iron deficiency without anaemia (ID). The reasons for the ID/IDA were
      hypermenorrhoea (HyM) (n = 170), post-partum condition (PP) (n = 53) or another
      indication (n = 53). The average age of the patients was 40 years old, with 8 %
      of them being vegetarians. Half of the patients had already been treated for
      anaemia, primarily with oral iron products (94 %). The primary, serious
      accompanying symptoms of anaemia were fatigue (72 %), lack of concentration (42
      %), pale mucous membranes (42 %), headache (26 %) and sleep disorders (21 %).
      Only one patient did not show serious symptoms at the start of the study. The
      most frequent indications for parenteral therapy were the need for rapid iron
      substitution to reduce symptoms (> 70 %), followed by the lower effectiveness or
      intolerance of oral products (42 % each) as well as patients not completing the
      course of treatment with oral products (12 %). Patient information was collected
      at both the beginning and the end of the observation period, which lasted 15
      weeks on average. FCM was most frequently administered via infusion (92 %;
      average infusion duration 21 minutes). Seven percent of patients received bolus
      injections. The average total iron dosage per patient was 788.7 mg (median 550
      mg; range: 50-3000 mg); the median individual dosage was 500 mg (range: 50-1000
      mg). The total dosage was, in most cases, administered through a single
      application (range: 1-10). Symptoms, blood values (Hb), iron stores (serum
      ferritin [S-ferritin]) and transport iron (transferrin saturation [TSAT])
      normalised to a large extent. In all subgroups, 92 % of women displayed a marked
      improvement in all of their symptoms. The average increase in Hb-value in the
      group as a whole was statistically significant, increasing from 10.5 to 13.0
      g/dl. In the group with anaemia, the value increased from 9.9 to 13.3 g/dl, with
      80 % of women reaching normal Hb-values. The average S-ferritin value increased
      by a statistically significant > 70 ug/L from 17.2 to 88.8 ug/l and the value for
      the TSAT increased from 16.3 % to 22.8 %. Seven patients reported experiencing
      side effects. None of the results were severe. Overall, as part of this non
      interventional study for everyday routine in a gynaecological practice, a rapid
      improvement in symptoms accompanied by the rectification of iron deficiency and
      anaemia was shown with low occurrences of mild undesirable events, and therefore
      the data obtained from controlled clinical studies on the effectiveness and
      tolerance of intravenous ferric carboxymaltose could be confirmed.

PMID- 24741124
TI  - High-Intensity Focused Ultrasound Ablation of Uterine Fibroids - Potential Impact
      on Fertility and Pregnancy Outcome.
AB  - Laparoscopic myomectomy is regarded as the gold standard for women with
      symptomatic fibroids who wish to become pregnant. High-intensity focused
      ultrasound (HIFU or MRgFUS) ablation of uterine fibroids is also being discussed
      as a non-surgical, minimally invasive, therapeutic option. This review examines
      the available data on the impact of HIFU/MRgFUS on fertility and pregnancy,
      focusing particularly on potential direct side-effects of this type of
      intervention on ovaries, fallopian tubes and uterus and potential late effects on
      pregnancy and birth, based on the current literature. All pregnancies after
      HIFU/MRgFUS published to date (around 100 cases) were evaluated. The published
      case series suggest that HIFU/MRgFUS ablation has no impact on the rate of
      miscarriages or other obstetrical outcome parameters. Because no prospective
      studies exist which permit firm conclusions to be drawn on the impact of
      HIFU/MRgFUS on fertility and pregnancy outcome in women with symptomatic
      fibroids, this approach is currently only recommended for women with suspected
      fertility problems due to uterine fibroids who either decline surgery or who have
      an unacceptably high surgical risk.

PMID- 24741125
TI  - Comparison of Obstetric Efficacy and Safety of the Kiwi OmniCup with Conventional
      Vacuum Extraction.
AB  - Purpose: The aim of the present study was to compare the safety and efficacy of
      the Kiwi OmniCup system with conventional vacuum delivery. Methods: A
      retrospective study of operative vaginal deliveries was done for 4682 births. The
      procedures included 217 operative vaginal deliveries (4.6 %), 79 of which were
      done using conventional vacuum extraction (37 %) and 138 using the Kiwi system
      (63 %). Results: Use of the Kiwi system was associated with a significant
      reduction in episiotomies (61 vs. 76 % in the control group; p < 0.05). The rates
      of successful completion of birth were comparable for the two systems (94 % with
      the Kiwi system and 99 % with conventional vacuum delivery). Cup detachment
      occurred significantly more often in the Kiwi group (p < 0.005), requiring a
      change to a different method of birth significantly more often. It was necessary
      to change the procedure significantly more often from the mid-pelvis (p < 0.05).
      The incidence of maternal and foetal injuries was similar for the two systems.
      Conclusions: With regard to obstetric efficacy and safety and foetal and maternal
      injuries, the Kiwi system is an acceptable alternative to the conventional vacuum
      cup. The advantages of the Kiwi system are its significantly lower episiotomy
      rate and its ease and rapidity of use.

PMID- 24741126
TI  - iPads in Breast Imaging - A Phantom Study.
AB  - Introduction: Modern tablet PCs as the iPad are becoming more and more integrated
      into medicine. The aim of this study was to evaluate the display quality of iPads
      regarding digital mammography. Materials and Methods: Three experienced readers
      compared the display quality of the iPad 2 and 3 with a dedicated 10 megapixel
      (MP) mammography liquid crystal display (LCD) screen in consensus using the
      standardized Contrast Detail Mammography (CDMAM) phantom. Phantom fields without
      agreement between the readers were classified as "uncertain", correct 2 : 1
      decisions were classified as "uncertain/readable". In a second step display
      quality of the three reading devices was judged subjectively in a side by side
      comparison. Results: The 10 MP screen was superior to both iPads in 4 (phantom
      )fields and inferior in 2 fields. Comparing the iPads, version 3 was superior in
      4 fields and version 2 was superior in 1 field. However these differences were
      not significant. Total number of "uncertain" fields did not show significant
      differences. The number of "uncertain" fields was 15 with the 10 MP screen, 16
      with the iPad 2 and 17 with the iPad 3 (p > 0.05), the number of
      "uncertain/readable" fields was 4, 7 and 8, respectively. Subjective image
      quality of the iPad 3 and the 10 MP screen was rated superior to the iPad 2.
      Conclusion: The evaluated iPads, especially in version 3, seem to be adequate to
      display mammograms in a diagnostic quality and thus could be useful e.g. for
      patient consultation, clinical demonstration or educational and teaching
      purposes. However primary mammogram reading should still be performed on
      dedicated large sized reading screens.

PMID- 24741127
TI  - Culture of Individually Required Number of 2-Pronuclei-Stage Oocytes - Patient
      Participation in Decision-Making is in Accordance with the Aim of Avoiding
      Surplus Embryo Freezing.
AB  - Background: The aim of this study was to evaluate how many embryos will develop
      if more than 3 2-pronuclei-stage oocytes (2-PNOs) are cultured at the patient's
      request and in accordance with the Germany Embryo Protection Law. Methods: A
      total of 106 cycles of patients undergoing their 1st, 2nd or 3rd cycle of IVF or
      ICSI treatment in 2010 were prospectively included in the study. In each
      individual case, a decision was taken prior to treatment about the number of 2
      PNOs to be cultured after each cycle. Results: Ninety female patients were
      treated for a total of 106 cycles. A mean of two to six 2-PNOs were cultivated
      for a period of between 3 and 6 days for each patient. After culture, no viable
      embryo was identified for 5 patients (4.7 %), a single viable embryo was
      identified for 37 cycles (34.7 %), and 2 viable embryos were identified for 52
      cycles (48.8 %). Eleven patients (10.3 %) had 3 viable embryos after a further 11
      cycles and 1 patient had 4 viable embryos in a single cycle. Ten of the patients
      with 3 embryos each opted to have all 3 embryos transferred in the same cycle.
      This meant that a single embryo from one patient with 3 viable embryos and a
      single embryo of the patient with 4 viable embryos were cryopreserved after
      culture. The pregnancy rate was 19 % per embryo transfer and 25 % per blastocyst
      transfer (20 pregnancies in total). All cryopreserved embryos were transferred in
      a subsequent cycle. Discussion: Based on this study it is possible to make a
      statement about the number of viable embryos which should be cultivated to
      obtain, at best, two embryos for transfer without running an unacceptably high
      risk of producing too many embryos which would then need to be cryopreserved.
      Only 12 patients (13.3 %) had more than 2 viable embryos. The number of
      supernumerary pre-implantation-stage embryos was acceptably low (only 2 patients
      had additional viable embryos, 2.2 %). This means that it is possible to fulfil
      the wishes of individual patients while complying with the German Embryo
      Protection Law.

PMID- 24741128
TI  - Working and Training Conditions of Gynecology Residents in North Rhine-Westfalia,
      Germany.
AB  - Introduction: In 2002, gynecology residents in North Rhine-Westfalia (NRW) were
      asked how satisfied they were with their working and training conditions. A new
      extended survey of gynecology residents aimed to evaluate whether changes to
      specialist training regulations had affected residents' levels of job
      satisfaction and to identify areas where training conditions still urgently
      required improvement. Material and Methods: A total of 1223 questionnaires with
      52 questions were sent to the 159 gynecology clinics in NRW. Responses could be
      dichotomous, multi-level or quantitative. The results were analyzed with regard
      to age, gender, family status and type of clinic and were additionally compared
      with the results of a previous survey. Results: The percentage of women residents
      has increased to 84.6 %. A workload of more than 48 hours per week has resulted
      in decreased motivation and lower levels of satisfaction during training,
      although overall levels of satisfaction have clearly improved compared to the
      previous survey. Use of a logbook to create a more structured training program
      has not achieved the desired effect. Nevertheless, seven of eight gynecology
      residents would study medicine again, although 28 % of the budding gynecologists
      are considering working abroad or in private industry. Conclusion: Both training
      and overall satisfaction with working conditions must be improved to preserve the
      appeal of gynecology for young academics. This survey aims to identify key
      factors which are responsible for (dis)satisfaction with working conditions.

PMID- 24741129
TI  - 23-Year-Old Female with an Inflammatory Myofibroblastic Tumour of the Breast: A
      Case Report and a Review of the Literature.
AB  - Purpose: Inflammatory myofibroblastic tumours (IMT) are a subcategory of
      inflammatory pseudotumours (IPT). They arise most commonly in the abdominopelvic
      region, lung and retroperitoneum, but virtually any anatomical site may be
      involved. Predominantly children and adolescents are affected and there is a
      tendency for local recurrence. In the literature up to the present, 20 patients
      have been reported with an IPT/IMT of the breast. We would like to present
      another patient with this unusual tumour entity of the breast and discuss the
      literature. Patient and Examinations: A 23-year-old woman presented with a
      painless lump in her left breast. There was no history of breast cancer in her
      family. Sonography showed a hypoechoic heterogeneous solid mass with irregular
      margins. A core needle biopsy revealed a tumour of high cellularity and a densely
      collagenous background. Immunohistochemically, the spindle-shaped cells were
      immunoreactive to smooth muscle actin and ALK-1 protein. Additional FISH analysis
      proved ALK rearrangements on chromosome 2p23 leading to the diagnosis of an IMT.
      Wide surgical excision was performed with no evidence of local recurrence after
      12 months. Conclusion: Three of the above mentioned 20 patients with IMT/IPT of
      the breast developed a recurrent tumour, none presented with distant metastasis.
      A significant recurrence rate of 15 % leads to a clinically and sonographically
      close follow-up in these patients.

PMID- 24741130
TI  - Optimization of a Model Corrected Blood Input Function from Dynamic FDG-PET
      Images of Small Animal Heart In Vivo.
AB  - Quantitative evaluation of dynamic Positron Emission Tomography (PET) of mouse
      heart in vivo is challenging due to the small size of the heart and limited
      intrinsic spatial resolution of the PET scanner. Here, we optimized a compartment
      model which can simultaneously correct for spill over and partial volume effects
      for both blood pool and the myocardium, compute kinetic rate parameters and
      generate model corrected blood input function (MCBIF) from ordered subset
      expectation maximization - maximum a posteriori (OSEM-MAP) cardiac and
      respiratory gated 18F-FDG PET images of mouse heart with attenuation correction
      in vivo, without any invasive blood sampling. Arterial blood samples were
      collected from a single mouse to indicate the feasibility of the proposed method.
      In order to establish statistical significance, venous blood samples from n=6
      mice were obtained at 2 late time points, when SP contamination from the tissue
      to the blood is maximum. We observed that correct bounds and initial guesses for
      the PV and SP coefficients accurately model the wash-in and wash-out dynamics of
      the tracer from mouse blood. The residual plot indicated an average difference of
      about 1.7% between the blood samples and MCBIF. The downstream rate of myocardial
      FDG influx constant, Ki (0.15+/-0.03 min-1), compared well with Ki obtained from
      arterial blood samples (P=0.716). In conclusion, the proposed methodology is not
      only quantitative but also reproducible.

PMID- 24741131
TI  - Cultivate... research an attitude and learning a passion.

PMID- 24741132
TI  - The timing of surgery in lumbar disc prolapse: A systematic review.
AB  - Herniation of nucleus pulposus leading to leg pain is the commonest indication
      for lumbar spine surgery. However, there is no consensus when to stop
      conservative treatment and when to consider for surgery. A systematic review of
      literature was done to find a consensus on the issue of when should surgery be
      performed for herniation of nucleus pulposus in lumbar spine was conducted.
      Electronic database searches of Medline, Embase and Pubmed Central were performed
      to find articles relating to optimum time to operate in patients with herniation
      of nucleus pulposus in lumbar spine, published between January 1975 and 10
      December 2012. The studies were independently screened by two reviewers.
      Disagreements between reviewers were settled at a consensus meeting. A scoring
      system based on research design, number of patients at final followup, percentage
      of patients at final followup, duration of followup, journal impact factor and
      annual citation index was devised to give weightage to Categorize (A, B or C)
      each of the articles. Twenty one studies fulfilled the criteria. Six studies were
      of retrospective design, 13 studies were of Prospective design and two studies
      were randomized controlled trials. The studies were categorized as: Two articles
      in category A (highest level of evidence), 12 articles in category B (moderate
      level of evidence) while seven articles in Category C (poor level of evidence).
      Category A studies conclude that duration of sciatica prior to surgery made no
      difference to the outcome of surgery in patients with herniation of nucleus
      pulposus in the lumbar spine. Ten out of 12 studies in Category B revealed that
      longer duration of sciatica before surgery leads to poor results while 2 studies
      conclude that duration of sciatica makes no difference to outcome. In category C,
      five studies conclude that longer duration of sciatica before surgery leads to
      poor outcome while two studies find no difference in outcome with regards to
      duration of sciatica. A qualitative and quantitative analysis was performed which
      favoured the consensus that longer duration of sciatica leads to poorer outcome.
      A systematic and critical review of literature revealed that long duration of
      preoperative leg pain lead to poor outcome for herniation of nucleus pulposus.
      Only a broad time frame (2-12 months) could be derived from the review of
      literature due to lack of high quality studies and variable and contrasting
      results of the existing studies. While surgery performed within six months was
      most commonly found to lead to good outcome of surgery, further studies are
      needed to prove this more conclusively. At this stage it is felt that time alone
      should not be the basis of recommending surgery and multiple other variables
      should be considered in a shared decision making process between the surgeon and
      the patient. 

PMID- 24741134
TI  - Retraction notice.

PMID- 24741133
TI  - Tubercular spondylitis in children.
AB  - Spine of the child has unique anatomy and growth potential to grow to adult size.
      Tuberculosis (TB) spine results in bone loss as well as disturbed growth
      potential, hence spinal deformities may progress as the child grows. The growth
      potential is also disturbed when the disease focus is surgically intervened.
      Surgery is indicated for complications such as deformity, neurological deficit,
      instability, huge abscess, diagnostic dilemma and in suspected drug resistance to
      mycobacterium tuberculosis. The child on antitubercular treatment needs to be
      periodically evaluated for weight gain and drug dosages need to be adjusted
      accordingly. The severe progressive kyphotic deformity should be surgically
      corrected. Mild to moderate cases should be followed up until maturity to observe
      progression/improvement of spinal deformity. The surgical correction of kyphotic
      deformity in active disease is less hazardous than in a healed kyphosis. The
      internal kyphectomy by extra pleural approach allows adequate removal of internal
      salient in paraplegic patients with healed kyphotic deformity. 

PMID- 24741135
TI  - Unstable Jefferson fractures: Results of transoral osteosynthesis.
AB  - BACKGROUND: Majority of C1 fractures can be effectively treated conservatively by
      immobilization or traction unless there is an injury to the transverse ligament.
      Conservative treatment usually involves a long period of immobilization in a halo
      vest. Surgical intervention generally involves fusion, eliminating the motion of
      the upper cervical spine. We describe the treatment of unstable Jefferson
      fractures designed to avoid these problems of both conservative and invasive
      methods. MATERIALS AND METHODS: A retrospective review of 12 patients with
      unstable Jefferson fractures treated with transoral osteosynthesis of C1 between
      July 2008 and December 2011 was performed. A steel plate and C1 lateral mass
      screw fixation were used to repair the unstable Jefferson fractures. Our study
      group included eight males and four females with an average age of 33 years
      (range 23-62 years). RESULTS: Patients were followed up for an average of 16
      months after surgery. Range of motion of the cervical spine was by and large
      physiologic: Average flexion 35 degrees  (range 28-40 degrees ), average
      extension 42 degrees  (range 30-48 degrees ). Lateral bending to the right and
      left averaged 30 degrees  and 28 degrees  respectively (range 12-36 degrees  and
      14-32 degrees  respectively). The average postoperative rotation of the
      atlantoaxial joint, evaluated by functional computed tomography scan was 60
      degrees  (range 35-72 degrees ). Total average lateral displacement of the
      lateral masses was 7.0 mm before surgery (range 5-12 mm), which improved to 3.5
      mm after surgery (range 1-6.5 mm). The total average difference of the atlanto
      dens interval in flexion and extension after surgery was 1.0 mm (range 1-3 mm).
      CONCLUSIONS: Transoral osteosynthesis of the anterior ring using C1 lateral mass
      screws is a viable option for treating unstable Jefferson fractures, which allows
      maintenance of rotation at the C1-C2 joint and restoration of congruency of the
      atlanto-occipital and atlantoaxial joints.

PMID- 24741136
TI  - Outcome of single level anterior cervical discectomy and fusion using nano
      hydroxyapatite/polyamide-66 cage.
AB  - BACKGROUND: Cages have been widely used for the anterior reconstruction and
      fusion of cervical spine. Nonmetal cages have become popular due to prominent
      stress shielding and high rate of subsidence of metallic cages. This study aims
      to assess fusion with n-HA/PA66 cage following one level anterior cervical
      discectomy. MATERIALS AND METHODS: Forty seven consecutive patients with
      radiculopathy or myelopathy underwent single level ACDF using n-HA/PA66 cage. We
      measured the segmental lordosis and intervertebral disc height on preoperative
      radiographs and then calculated the loss of segmental lordosis correction and
      cage subsidence over followup. Fusion status was evaluated on CT scans. Odom
      criteria, Japanese Orthopedic Association (JOA) and Visual Analog Pain Scales
      (VAS) scores were used to assess the clinical results. Statistically quantitative
      data were analyzed while Categorical data by chi(2) test. RESULTS: Mean
      correction of segmental lordosis from surgery was 6.9 +/- 3.0 degrees  with a
      mean loss of correction of 1.7 +/- 1.9 degrees . Mean cage subsidence was 1.2 +/-
      0.6 mm and the rate of cage subsidence (>2 mm) was 2%. The rate of fusion success
      was 100%. No significant difference was found on clinical or radiographic
      outcomes between the patients (n=27) who were fused by n-HA/PA66 cage with pure
      local bone and the ones (n=20) with hybrid bone (local bone associating with bone
      from iliac crest). CONCLUSIONS: The n-HA/PA66 cage is a satisfactory
      reconstructing implant after anterior cervical discectomy, which can effectively
      promote bone graft fusion and prevent cage subsidence.

PMID- 24741137
TI  - Surgical treatment of thoracic disc herniations using a modified transfacet
      approach.
AB  - BACKGROUND: Ideal surgical treatment for thoracic disc herniation (TDH) is
      controversial due to variations in patient presentation, pathology, and possible
      surgical approach. Althougth discectomy may lead to improvements in neurologic
      function, it can be complicated by approach related morbidity. Various posterior
      surgical approaches have been developed to treate TDH, but the gold standard
      remains transthoracic decompression. Certain patients have comorbidities and
      herniation that are not optimally treated with an anterior approach. A transfacet
      pedicle approach was first described in 1995, but outcomes and complications have
      not been well described. The aim of this work was to evaluate the clinical effect
      and complications in a consecutive series of patients with symptomatic thoracic
      disc herniations undergoing thoracic discectomy using a modified transfacet
      approach. MATERIALS AND METHODS: 33 patients with thoracic disc herniation were
      included in this study. Duration of the disease was from 12 days to 36 months,
      with less than 1 month in 13 patients. Of these, 15 patients were diagnosed with
      simple thoracic disc herniation, 6 were associated with ossified posterior
      longitudinal ligament, and 12 with ossified or hypertrophied yellow ligament. A
      total of 45 discs were involved. All the herniated discs and the ossified
      posterior longitudinal ligaments were excised using a modified transfacet
      approach. Laminectomy and replantation were performed for patients with ossified
      or hypertrophied yellow ligament. The screw-rod system was used on both sides in
      14 patients and on one side in l9 patients. RESULTS: 29 patients were followed up
      for an average of 37 months (range 12-63 months) and 4 patients were lost to
      followup. Evaluation was based on Epstein and Schwall criteria.5 15 were
      classified as excellent and 10 as good, accounting for 86.21% (25/29); 2 patients
      were classified as improved and 2 as poor. All the patients recovered
      neurologically after surgery. A total of 25 patients had significantly improved
      motor function from 3 to 6 months after surgery and 10 patients had slow recovery
      6 months after surgery.. Of the three patients with postoperative complications,
      two had exacerbated preexisting defects and one had implant failure.
      Postoperative computed tomography or magnetic resonance imaging showed that all
      patients had well fused replanted lamina and completely decompressed canal.
      CONCLUSION: Thoracic discectomy using a modified transfacet approach can
      significantly improve the clinical outcomes.

PMID- 24741138
TI  - Percutaneous vertebroplasty in painful refractory vertebral hemangiomas.
AB  - BACKGROUND: Painful vertebral hemangiomas are often inadequately managed
      medically. We evaluated the outcome of percutaneous vertebroplasty (PVP) in the
      treatment of painful vertebral hemangiomas refractory to medical management.
      MATERIALS AND METHODS: 14 patients (four thoracic and ten lumbar vertebra) with
      painful vertebral hemangiomas presenting with severe back pain for more than 6
      months not responding to medical therapy were treated by vertebroplasty. Cross
      sectional imaging of the spine with magnetic resonance was done. Blood
      investigations were done to exclude coagulopathy excluded. PVP was performed
      under local anesthesia. RESULTS: The pain intensity numeric rating scale (PI-NRS
      11) of these patients was in the range of 7-10 (Severe Pain). After
      vertebroplasty 8 patients were completely free of pain (PI NRS Score 0) while 6
      were significantly relieved (PI-NRS Score 1-3). No complications were observed.
      Two patients with associated radicular pain had good pain relief following PVP.
      No recurrence was found during 36 months of postoperative followup. CONCLUSION:
      PVP is a safe and effective procedure in patients with painful vertebral
      hemangiomas refractory to medical management.

PMID- 24741139
TI  - Longitudinal study of body composition in spinal cord injury patients.
AB  - BACKGROUND: Bone mass loss and muscle atrophy are the frequent complications
      occurring after spinal cord injury (SCI). The potential risks involved with these
      changes in the body composition have implications for the health of the SCI
      individual. Thus, there is a need to quantitate and monitor body composition
      changes accurately in an individual with SCI. Very few longitudinal studies have
      been reported in the literature to assess body composition and most include
      relatively small number of patients. The present prospective study aimed to
      evaluate the body composition changes longitudinally by DEXA in patients with
      acute SCI. MATERIALS AND METHODS: Ninety five patients with acute SCI with
      neurological deficits were evaluated for bone mineral content (BMC), body
      composition [lean body mass (LBM) and fat mass] by dual-energy X-ray
      absorptiometry during the first year of SCI. RESULTS: There was a significant
      decrease in BMC (P < 0.05) and LBM (P < 0.05) and increase in total body fat mass
      (TBFM) and percentage fat at infra-lesional sites. The average decrease was 14.5%
      in BMC in lower extremities, 20.5% loss of LBM in legs and 15.1% loss of LBM in
      trunk, and increase of 0.2% in fat mass in legs and 17.3% increased fat in the
      lower limbs at 1 year. The tetraplegic patients had significant decrease in arm
      BMC (P < 0.001), arm LBM (P < 0.01) and fat percentage (P < 0.01) compared to
      paraplegics. Patients with complete motor injury had higher values of TBFM and
      fat percentage, but comparable values of BMC and LBM to patients with incomplete
      motor injury. CONCLUSIONS: Our findings suggest that there is a marked decrease
      in BMC and LBM with increase in adiposity during the first year of SCI. Although
      these changes depend on the level and initial severity of lesions, they are also
      influenced by the neurological recovery after SCI.

PMID- 24741140
TI  - Large blood vessel stretch in lumbar spine through anterior surgical approach: An
      experimental study in adult goat.
AB  - BACKGROUND: Various anterior lumbar surgical approaches, including the minimally
      invasive approach, have greatly improved in recent years. Vascular complications
      resulting from ALIF are frequently reported. Little information is available
      about the safety of large blood vessel stretch. We evaluated the right side
      stretch limit (RSSL) of the abdominal aorta (AAA) and the inferior vena cava
      (IVC) without blood flow occlusion and investigated stretch-induced histological
      injury and thrombosis in the iliac and femoral arteries and veins and the
      stretched vessels. MATERIALS AND METHODS: The RSSL of blood vessels in five adult
      goats was measured by counting the number of 0.5-cm-thick wood slabs that were
      inserted between the right lumbar edge and the stretch hook. Twenty seven adult
      goats were divided into three groups to investigate histological injury and
      thrombosis under a stretch to 0.5 cm (group I) 1.5 cm (group II) for 2 h, or no
      stretch (group III). Blood vessel samples from groups I and II were analyzed on
      postsurgical days 1, 3, and 7. Thrombogenesis was examined in the iliac and
      femoral arteries and veins. RESULTS: The RSSL of large blood vessels in front of
      L4/5 was 1.5 cm from the right lumbar edge. All goats survived surgery without
      complications. No injury or thrombosis in the large blood vessels in front of the
      lumbar vertebrae and in the iliac or femoral arteries and veins was observed.
      Under light microscopy, group I showed slight swelling of endothelial cells in
      the AAA and no histological injury of the IVC. The AAA of group II showed
      endothelial cell damage, unclear organelles, and incomplete cell connections by
      electron microscopy. CONCLUSIONS: The AAA and IVC in a goat model can be
      stretched by <=0.5 cm, with no thrombosis in the AAA, IVC, iliac or femoral
      arteries and veins.

PMID- 24741141
TI  - Effect of thoracic arthrodesis in prepubertal New Zealand white rabbits on cardio
      pulmonary function.
AB  - BACKGROUND: This experimental study was aimed at evaluating the type of cardiac
      and pulmonary involvement, in relation to changes of the thoracic spine and cage
      in prepubertal rabbits with nondeformed spine following dorsal arthrodesis. The
      hypothesis was that T1-T12 arthrodesis modified thoracic dimensions, but would
      not modify cardiopulmonary function once skeletal maturity was reached. MATERIALS
      AND METHODS: The study was conducted in 16 female New Zealand White (NZW)
      rabbits. Nine rabbits were subjected to T1-T12 dorsal arthrodesis while seven
      were sham-operated. Echocardiographic images were obtained at 12 months after
      surgery and parameters for 2-dimensional and M-mode echocardiographic variables
      were assessed. One week before echocardiographic examination, blood samples were
      withdrawn from the animals' central artery of the left ear to obtain blood gas
      values. One week after echocardiographic assessment, a thoracic CT scan was
      performed under general anesthesia. Chest depth (CD) and width (CW), thoracic
      kyphosis (ThK) and sternal length (StL) were measured; thoracic index (ThI),
      expressed as CD/CW ratio. All subjects were euthanized after the CT scan. Heart
      and lungs were subsequently removed to measure weight and volume. RESULTS: The
      values for 2-dimensional and M-mode echocardiographic variables were found to be
      uniformly and significantly higher, compared to those reported in anesthetized
      rabbits. CD, ThK, and StL were considerably lower in operated rabbits, as
      compared to the ones that were sham-operated. Similarly, the ThI was lower in
      operated rabbits than in sham-operated ones. CONCLUSION: Irregularities in
      thoracic cage growth resulting from thoracic spine arthrodesis did not alter
      blood and echocardiographic parameters in NZW rabbits.

PMID- 24741142
TI  - Acromioclavicular joint acceleration-deceleration injury as a cause of persistent
      shoulder pain: Outcome after arthroscopic resection.
AB  - BACKGROUND: Shoulder pain in general and acromioclavicular joint (ACJ) pain
      specifically is common after acceleration-deceleration injury following road
      traffic accident (RTA). The outcome of surgical treatment in this condition is
      not described in the literature. The aim of the present study was to report the
      outcome of arthroscopic resection of the ACJ in these cases. MATERIALS AND
      METHODS: Nine patients with localized ACJ pain, resistant to nonoperative
      treatment were referred on an average 18 months after the injury. There were 3
      male and 6 females. The right shoulder was involved in seven patients and the
      left in two. The average age was 38.9 years (range 29-46 years). All presented
      with normal X-rays but with torn acromioclavicular joint disc and effusion on
      magnetic resonance imaging (MRI). Arthroscopic ACJ excision arthroplasty was
      performed in all patients. RESULTS: At a mean followup of 18 month, all patients
      had marked improvement. The Constant score improved from 36 to 81, the pain score
      from 3/15 to 10/15 and the patient satisfaction improved from 3.5/10 to 9.3/10.
      CONCLUSION: Arthroscopic ACJ excision arthroplasty, gives good outcomes in
      patients not responding to conservative management in ACJ acceleration
      deceleration injury.

PMID- 24741143
TI  - Mucoid degeneration of the anterior cruciate ligament: Management and outcome.
AB  - BACKGROUND: Mucoid degeneration (MD) is a rare pathological affection of the
      anterior cruciate ligament (ACL). Mucinous material within the substance of ACL
      produces pain and limited motion in the knee. This series describes the
      clinicoradiological presentation of patients with mucoid ACL, partial
      arthroscopic debridement of ACL and outcomes. MATERIALS AND METHODS: During a
      period of 3 years, 11 patients were included based upon the clinical suspicion,
      magnetic resonance imaging (MRI) findings, arthroscopic features and
      histopathologic confirmation of MD of ACL. RESULT: Six patients were male and
      five were female with median age of 40 years (range 21-59 years). All patients
      complained of knee pain with median duration of 5 months (range 1-24 months). All
      patients had painful deep flexion with 63.6% (N = 7) reporting trivial trauma
      before the onset of symptoms. MRI revealed MD of ACL in all with associated cyst
      in three patients. Partial debridement of ACL was done in ten and complete in one
      patient. None of them required notchplasty. Histopathology confirmed the
      diagnosis in all of them. At the mean followup of 13.81 months (range 6-28
      months), all patients regained complete flexion and none complained of
      instability. CONCLUSION: Prior knowledge of condition with high index of
      suspicion and careful interpretation of MRI can establish the diagnosis
      preoperatively. It responds well to partial debridement of ACL and mucinous
      material without development of instability.

PMID- 24741144
TI  - The effect of patient position during trauma surgery on fat embolism syndrome: An
      experimental study.
AB  - BACKGROUND: The aim of this study was to compare the effect of supine versus
      lateral position on clinical signs of fat embolism during orthopedic trauma
      surgery. Dogs served as the current study model, which could be extended and/or
      serve as a basis for future in vivo studies on humans. It was hypothesized that
      there would be an effect of position on clinical signs of fat embolism syndrome
      in a dog model. MATERIALS AND METHODS: 12 dogs were assigned to supine (n = 6)
      and lateral (n = 6) position groups. Airway pressures, heart rate, blood
      pressure, cardiac output, pulmonary artery pressure, pulmonary artery wedge
      pressure, right atrial pressure, arterial and venous blood gases, white blood
      count, platelet count and neutrophil count were obtained. Dogs were then
      subjected to pulmonary contusion in three areas of one lung. Fat embolism was
      generated by reaming one femur and tibia, followed by pressurization of the
      canal. RESULTS: No difference was found in any parameters measured between supine
      and lateral positions at any time (0.126 < P < 0.856). CONCLUSIONS: The position
      of trauma patients undergoing reamed intramedullary nailing did not alter the
      presentation of the features of the lung secondary to fat embolism.

PMID- 24741145
TI  - Corrective surgery for deformity of the upper cervical spine due to ankylosing
      spondylitis.
AB  - Rotational and flexion deformity of C1-C2 due to ankylosing spondylitis is rare.
      We did surgical correction in one such case by lateral release, resection of the
      posterior arch of C1 and mobilization of the vertebral arteries, wedge osteotomy
      of the lateral masses of C1 and internal fixation under general anesthesia. There
      were no vascular and neurological complications during the surgery. After
      operation the atlantoaxial rotational deformity was corrected and the normal
      cervical lordosis was restored. At 1 year followup his visual field and feeding
      became normal and internal fixation was stable. 

PMID- 24741146
TI  - Recurrent primary lumbar vertebra chondrosarcoma: Marginal resection and Iodine
      125 seed therapy.
AB  - Chondrosarcomas are uncommon in the spinal column. En bloc excisions with wide
      margins are of critical importance but not always feasible in spine. We report
      the outcome in a case of recurrent lumbar vertebral chondrosarcoma treated with
      marginal resection and iodine-125 seeds placed in the resected tumor bed. 

PMID- 24741147
TI  - Disseminated Fusarium oxysporum neurospinal infection.
AB  - We report a case of disseminated meningospondylodiscitis in an elderly diabetic
      patient caused by Fusarium oxysporum. As the clinical presentation was
      nonspecific, the diagnosis of the condition could only be arrived at after
      laboratory and imaging studies. The diagnosis of the condition requires a high
      index of suspicion. Patient underwent thorough surgical debridement along with a
      short course of variconazole and remained asymptomatic after 36 months of
      diagnosis. Fusarium is a large genus of filamentous fungi widely distributed in
      soil and in association with plants. It is known to cause local infections (nail,
      cornea) in healthy humans and disseminated infection only in the
      immunocompromised. 

PMID- 24741148
TI  - Double crush syndrome due to plating of humeral shaft fracture.
AB  - Median nerve injury is rarely associated with the humeral shaft fracture. A Sixty
      two year old woman with a displaced humeral shaft fracture, developed a
      symptomatic carpal tunnel syndrome after plating with a screw protruding
      medially. 16 months later, the implants were removed and the symptoms gradually
      improved without carpal tunnel release surgery. A double crush syndrome resulted
      due to the proximal compression by the medially protruding screw and the distal
      compression by carpal tunnel. The proximal decompression produced by removal of
      the screw led to relief of the symptoms. 

PMID- 24741149
TI  - Four quadrant parallel peripheral screw fixation for displaced femoral neck
      fractures in elderly patients.

PMID- 24741150
TI  - Author's reply.

PMID- 24741151
TI  - Four quadrant parallel peripheral screw fixation for displaced femoral neck
      fracture in elderly patients.

PMID- 24741152
TI  - Author's reply.

PMID- 24741153
TI  - A tribute: Dr. Mangalore Gopal Kini (1893-1952).

PMID- 24741154
TI  - Artificial sweeteners - a review.
AB  - Now a days sugar free food are very much popular because of their less calorie
      content. So food industry uses various artificial sweeteners which are low in
      calorie content instead of high calorie sugar. U.S. Food and Drug Administration
      has approved aspartame, acesulfame-k, neotame, cyclamate and alitame for use as
      per acceptable daily intake (ADI) value. But till date, breakdown products of
      these sweeteners have controversial health and metabolic effects. On the other
      hand, rare sugars are monosaccharides and have no known health effects because it
      does not metabolize in our body, but shows same sweet taste and bulk property as
      sugar. Rare sugars have no such ADI value and are mainly produced by using
      bioreactor and so inspite of high demand, rare sugars cannot be produced in the
      desired quantities. 

PMID- 24741155
TI  - Composition, functional properties and in vitro antioxidant activity of protein
      hydrolysates prepared from sardinelle (Sardinella aurita) muscle.
AB  - Composition, functional properties and in vitro antioxidative activities of
      protein hydrolysates prepared from muscle of sardinelle (Sardinella aurita) were
      investigated. Sardinelle protein hydrolysates (SPH) were obtained by treatment
      with crude enzyme preparations from Bacillus pumilus A1 (SPHA1), Bacillus
      mojavensis A21 (SPHA21) and crude enzyme extract from sardinelle (Sardinella
      aurita) viscera (SPHEE). The protein hydrolysates SPHA1, SPHA21 and SPHEE
      contained high protein content 79.1%, 78.25% and 74.37%, respectively. The
      protein hydrolysates had an excellent solubility and possessed interfacial
      properties, which were governed by their concentrations. The antioxidant
      activities of protein hydrolysates at different concentrations were evaluated
      using various in vitro antioxidant assays, including 1,1-diphenyl-2
      picrylhydrazyl (DPPH) radical method, reducing power assay, chelating activity,
      beta-carotene bleaching and DNA nicking assay. All protein hydrolysates showed
      varying degrees of antioxidant activity. SPHA21 had the highest DPPH radical
      scavenging activity (89% at 6 mg/ml) and higher ability to prevent bleaching of
      beta-carotene than SPHA1 and SPHEE (p < 0.05). However, SPHEE exhibited the
      highest metal chelating activity (89% at 1 mg/ml) and the strongest protection
      against hydroxyl radical induced DNA breakage (p < 0.05). 

PMID- 24741156
TI  - Provitamin A carotenoids in biofortified maize and their retention during
      processing and preparation of South African maize foods.
AB  - Provitamin A-biofortified maize may contribute to alleviating vitamin A
      deficiency (VAD), in developing countries. However, processing the maize into
      food products may reduce its provitamin A content. The aims of this study were to
      determine the composition of provitamin A carotenoids in biofortified maize
      varieties as well as to assess their retention during processing of popular maize
      foods consumed in KwaZulu-Natal, South Africa. The non-provitamin A carotenoid,
      zeaxanthin and the provitamin A carotenoids, beta-cryptoxanthin, and trans and
      cis isomers of beta-carotene, and other unidentified trans and cis isomers of
      beta-carotene were detected in varying concentrations in the maize. Milling
      provitamin A-biofortified maize into mealie meal resulted in a higher retention
      of carotenoids compared to milling into samp. The highest retention of provitamin
      A carotenoids was observed in cooked phutu and cooked samp, whilst cooking into
      thin porridge resulted in the lowest retention of provitamin A carotenoids. In
      phutu, 96.6 +/- 20.3% beta-cryptoxanthin and 95.5 +/- 13.6% of the beta-carotene
      were retained after cooking. In samp, 91.9 +/- 12.0% beta-cryptoxanthin and 100.1
      +/- 8.8% beta-carotene; and in thin porridge, 65.8 +/- 4.6% beta-cryptoxanthin
      and 74.7 +/- 3.0% beta-carotene were retained after cooking. This study
      demonstrates that provitamin A retention in maize is affected by the cooking
      method (and hence cooked food form) and therefore cooking methods that result in
      a good retention of provitamin A need to be identified and recommended. 

PMID- 24741157
TI  - Effect of treatments and packaging on the quality of dried carrot slices during
      storage.
AB  - The present investigation was undertaken to study the effect of treatments and
      packaging on the quality of dried carrot slices during storage. Carrot cultivar
      'Nantes' was sliced into 4.5 mm thick slices which were blanched in water at 95 
      degrees C for 4 min followed by dipping in 6% potassium metabisulphite (KMS)
      solution for 40 min and 350 ppm potassium sorbate solution for 10 min prior to
      two stage phase drying i.e. at 90 +/- 5  degrees C for 2 h and further drying at
      60 +/- 5  degrees C for 7 h in a cross-flow hot air cabinet dryer. The dried
      carrot slices were packed in 50 g packages of aluminium foil laminate (AFL)
      (polyethylene, aluminium foil and polyester) and high density polyethylene (HDPE)
      pouches having 32.5 MUm and 56.0 MUm thickness respectively and stored under
      ambient conditions i.e.18.5-29.1  degrees C temperature and 44.4-60.4% relative
      humidity for 6 months. Significant (p <= 0.05) increase was observed in the
      moisture content, water activity, reducing sugars and non-enzymatic browning
      while total solids, total soluble solids, titratable acidity, ascorbic acid,
      total sugars, pectin, rehydration ratio, sulphur dioxide, sorbic acid and
      carotenoids decreased significantly (p <= 0.05) during storage. Carrot slices pre
      treated with 6% KMS and packed in AFL pouches were found to retain best physico
      chemical quality. The curried product and soup prepared from dried slices from
      the same had highly acceptable sensory quality with initial overall acceptability
      scores 8.2 and 8.5 for curried slices and soup respectively on 9-point hedonic
      scale. The overall acceptability scores decreased from 8.2 to 7.9 and 8.5 to 7.7
      in curried product and soup respectively after 6 months storage. All the samples
      were microbially safe during 6 months of storage. 

PMID- 24741158
TI  - Effect of ice storage on the functional properties of proteins from a few species
      of fresh water fish (Indian major carps) with special emphasis on gel forming
      ability.
AB  - In the present study the effect of ice storage on physico-chemical and functional
      properties of proteins from Indian major carps with special emphasis on gel
      forming ability have been assessed for a period of 22 days. The solubility
      profile of proteins in high ionic strength buffer and calcium adenosine
      triphosphatase (ATPase) enzyme activity reduced significantly (p < 0.05), while
      that of total volatile base nitrogen (TVB-N) increased significantly (p < 0.05)
      at the end of 22 days of ice storage. The major protein fraction showed
      association-dissociation-denaturation phenomenon during ice storage as revealed
      by gel filtration profile and viscosity measurements. The gel forming ability of
      three fish species both in fresh and during different periods of ice storage was
      assessed by measuring the gel strength of heat induced gel. Among the three
      species the gel strength of the gel obtained from Catla catla and Cirrhinus
      mrigala was higher (586 and 561 g.cm) than the gel obtained from Labeo rohita
      (395 g.cm) in fresh condition. The gel forming ability of three species was
      significantly affected (p < 0.05) during ice storage. The TVB-N values of fish
      meat as a function of ice storage was within the prescribed limit up to 17 days
      of the ice storage. 

PMID- 24741159
TI  - Cloud-point extraction and reversed-phase high performance liquid chromatography
      for analysis of phenolic compounds and their antioxidant activity in Thai local
      wines.
AB  - A cloud-point extraction (CPE) was developed for the determination of 12 phenolic
      compounds (i.e. gallic acid, procatechuic acid, p-hydroxybenzoic acid, vanillic
      acid, caffeic acid, syringic acid, p-coumaric acid, ferulic acid, guaiacol, p
      cresol, o-cresol and 3,5-xylenol) using reversed-phase high performance liquid
      chromatography (RP-HPLC) with photodiode array (PDA) detection. The optimum CPE
      conditions were 2.0% (w/v) Triton X-114, 3.0% (w/v) Na2SO4 and 20-min
      equilibrated at 45  degrees C. The surfactant-rich phase was then analyzed by
      HPLC using a Symmetry C18 column, gradient mobile phase of acetonitrile and 1%
      (v/v) acetic acid, and PDA detection at 280 nm. Under the optimum condition, the
      target phenolic compounds were separated within 25 min. CPE gave higher
      enrichment factor up to 15-fold compared to that of direct analysis. The proposed
      method showed good analytical performances with limits of detection in the range
      0.01-0.1 mg L(-1) and precisions with relative standard deviation (RSD) lower
      than 5% for retention time and 10% for peak area. The method was successfully
      applied to the analysis of phenolic compounds in Thai local wine samples. Gallic
      acid, procatechuic acid, and vanillic acid were the highest phenolics found in
      the studied wines with the contents up to 172.4, 99.1, and 26.6 mg L(-1),
      respectively. The recovery of the spiked wine samples (0.5, 1.0, and 2.0 mg L(
      1)) were obtained in the range of 90.4-110%. High total phenolic content, total
      flavonoids, and antioxidant activity (DPPH method) in the studied wines were also
      observed. 

PMID- 24741160
TI  - Standardization of process parameters for microwave assisted convective
      dehydration of ginger.
AB  - Ginger (Zingiber Officinale, Cv. Suprava) slices (4 mm thick) were dehydrated at
      25 degrees , 40 degrees , 50 degrees  and 60  degrees C with three different
      microwave power levels, viz. 120, 240, and 360 W in microwave assisted convective
      dryer up to 0.07 g moisture/g dry solid to observe the feasibility of microwave
      assisted convective drying for ginger. The samples were also dried without
      application of microwaves (0 W) at the above air temperatures. The final product
      quality was compared in terms of rehydration characteristics, oleoresin and
      volatile oil contents, hardness, color and organoleptic quality. The maximum
      rehydration ratio of 3.86 +/- 0.06 was obtained at 50  degrees C without
      application of microwaves and was followed by 120 W-40  degrees C combination
      treatment (3.64 +/- 0.15). The minimum rehydration ratio was 2.34 +/- 0.20 for
      360 W with 60  degrees C. The yield of oleoresin content was higher for 120 W as
      compared to other power levels, which ranged between 5.12 +/- 0.85% and 6.34 +/-
      0.89%. The maximum retention of oleoresin was observed in case of 120 W-40 
      degrees C. The samples dried with microwave power level of 120 W also gave better
      yields of volatile oil as compared to other power levels. The best color was
      observed at 120 W-50  degrees C and 120 W-60  degrees C conditions with Hunter
      'a' (redness) values at 0.50 +/- 0.03 and 0.35 +/- 0.03, respectively. The
      sensory analysis also indicated that drying at 120 W-50  degrees C and 240 W-50 
      degrees C combinations gave the most acceptable quality product. Drying ginger
      with 120 W-50  degrees C combination helped in a saving of 53% and 44% in drying
      time as compared to hot air drying at 50 degrees  and 60  degrees C,
      respectively. Drying at 240 W-50  degrees C also gave a reasonably acceptable
      quality product with a net saving of 91% and 89% in drying time as compared to
      hot air drying at 50 degrees  and 60  degrees C, respectively. However, on the
      basis of rehydration characteristics, the acceptable process conditions were hot
      air drying at 50 degrees  or 60  degrees C, or with the 120 W-40  degrees C
      combination. 

PMID- 24741161
TI  - Optimization of weaning mix based on malted and extruded pearl millet and barley.
AB  - Weaning mix was developed using extrudates of plain and malted pearl millet
      (Pennisetum typhoides) and barley (Hordeum vulgare) flour. Central composite
      rotatable design (CCRD) with four independent variables PME (pearl millet
      extrudates), PMME (pearl millet malt extrudates), BE (barley extrudates), BME
      (barley malt extrudates) at five level and five dependent variables, i.e.
      lightness, peak viscosity (PV), water solubility index (WSI), water absorption
      index (WAI) and overall acceptability (OAA) scores, were used to conduct the
      experiments. Highly acceptable weaning mix was obtained by combining optimized
      ingredients with constant level of skim milk powder (SMP) 25%, WPC-70 5%, sugar
      6% and refined vegetable oil 4 ml 100 g(-1) mix. The optimized level of
      ingredients was PME 20.77%, PMME 7.39%, BE 20.99%, BME 6.53% with 81.3%
      desirability. The nutrient content of optimized weaning mix was in accordance
      with the standards specified by PFA, 2004. 

PMID- 24741162
TI  - Process optimization for the manufacture of lemon based beverage from hydrolyzed
      whey.
AB  - Whey obtained during the manufacture of Cheddar cheese and paneer was lactose
      hydrolyzed to develop lemon based whey beverage. The lactose present in whey was
      hydrolyzed by Maxilact L-2000 lactase enzyme. Maximum (85-90%) hydrolysis in
      cheese and paneer whey was optimized with enzyme concentration of 0.4% at pH 6.75
      after incubation at 40  degrees C for 3 h. The sweetness level in hydrolyzed whey
      was equivalent to 2.5% sucrose solution. Response surface methodology was used to
      optimize the levels of sugar, lemon juice, lemon flavor and stabilizer i.e.
      carboxyl methyl cellulose (CMC). The most acceptable lemon based beverage
      contained 8, 4, 0.1 and 0.05% of sugar, lemon juice, lemon flavor and CMC,
      respectively. The beverage had greater acceptability to judges after heat
      treatment at 90  degrees C for 2 min than the heat treatment of 5 psi for 5 min. 

PMID- 24741163
TI  - Effect of 1-methylcyclopropene and calcium chloride treatments on quality
      maintenance of 'Lingwu Long' Jujube fruit.
AB  - 'Lingwu Long' jujube (Zizyphus jujuba cv. Mill) fruits were harvested at mature
      green stages and then treated with 1.0 MUL L(-1) 1-methylcyclopropene (1-MCP),
      1.0% CaCl2 or their combination. All treatments were stored at room temperature
      (22 +/- 1  degrees C) and 80-90% relative humidity (RH) up for 15 days. Results
      indicated that 1.0 MUL L(-1) 1-MCP, 1.0% CaCl2 or their combination were
      effective in terms of senescence inhibition, and the storage life was extended by
      6, 4 and 9 days, respectively. 1-MCP and CaCl2 treatment had a synergic effect on
      the inhibition of ethylene production and microbial population of 'Lingwu Long'
      jujube fruit. The combination of 1-MCP and CaCl2 significantly reduced
      polygalacturonase (PG) and polyphenoloxidase (PPO) activities. It also maintained
      higher concentrations of titratable acid and ascorbic acid. 

PMID- 24741164
TI  - Effects of ultraviolet irradiation, pulsed electric field, hot water and ethanol
      vapours treatment on functional properties of mung bean sprouts.
AB  - The present investigation was conducted with the objective to study the effects
      of various treatments and storage conditions on ascorbic acid, total phenols,
      antioxidant activity and polyphenol oxidase activity of mung bean sprouts. The
      sprouts subjected to various treatments viz., pulsed electric field (PEF) (10,000
      V for 10 s), hot water dip (HWD) (50  degrees C for 2 min), ethanol vapours (1 h)
      and UV-Irradiation (10 kJm(-2) in laminar flow chamber for 1 h); and then stored
      at room (25 +/- 1  degrees C) and low (7 +/- 1  degrees C) temperature
      conditions. The sprouts were analyzed regularly at 24 h interval till end of
      shelf life. Different treatments given to sprouts resulted in differential effect
      on various parameters. The ascorbic acid, total phenols and antioxidant activity
      were highest in ethanol vapours treated sprouts. There was a general decrease in
      polyphenol oxidase activity by various treatments. During storage ascorbic acid,
      total phenols and antioxidant activity of sprouts first increased and then
      decreased significantly, however, for polyphenol oxidase activity a progressive
      increase with increase in storage period was observed. The trends were similar at
      room and low temperature storage conditions. Thus, it can be concluded that the
      ethanol vapours significantly improved the ascorbic acid content, total phenols
      and antioxidant activity of mung bean sprouts, both at room as well as low
      temperature conditions of storage. 

PMID- 24741165
TI  - Optimization of reaction parameters of acidolysis reaction between mustard oil
      and capric acid by using Thermomyces lanuginosus lipase.
AB  - Structured lipids were prepared from mustard oil by enzymatic acidolysis reaction
      with capric acid (C10) using lipase enzyme TLIM from Thermomyces lanuginosus as
      biocatalyst. Parameters such as substrate molar ratio, enzyme concentration,
      reaction temperature, stirring speed and time of maximum incorporation, were
      studied for the optimization of the reaction. The optimized set of process
      conditions was predicted by response surface methodology (RSM) and genetic
      algorithm (GA). The robustness of GA and RSM was evaluated using regression
      coefficient and p value. The R(2) found out by GA was 0.996 while from RSM was
      0.973. The results proved that GA models have better performance than RSM models.
      From the result, it could be concluded that optimal conditions for synthesis of
      capric acid rich mustard oil were: Temperature = 39.5  degrees C ; time = 21.1
      hr; Substrate ratio = 3.5; Enzyme content = 8.8%; Speed = 570.8 rpm. 

PMID- 24741166
TI  - Effects of cooking methods and temperatures on nutritional and quality
      characteristics of anchovy (Engraulis encrasicholus).
AB  - The aim of this study was to determine the nutritional and quality
      characteristics of anchovy after cooking. The fish were cooked by different
      methods (frying, baking and grilling) at two different temperatures (160  degrees
      C, 180  degrees C). Crude ash, crude protein and crude fat contents of cooked
      fish increased due to rise in dry matter contents. While cooking methods affected
      mineral content of anchovy, cooking temperature did not affect. The highest
      values of monounsaturated fatty acids were found in baked samples.
      Polyunsaturated fatty acids in baked samples were also high and similar in fried
      samples. Fried samples, which were the most preferred, lost its nutritional
      characteristics more than baked and grilled samples. Grilled and baked fish
      samples can be recommended for healthy consumption. However, grilled fish samples
      had hard texture due to more moisture loss than other methods. Therefore, it is
      concluded that baking is the best cooking method for anchovy. 

PMID- 24741167
TI  - Effect of glucose treatment on texture and colour of pidan white during storage.
AB  - Changes in texture and colour of pidan white as influenced by glucose treatment
      at levels of 0, 2 and 5% were determined after pickling (week 3) and during the
      storage up to 12 weeks. Hardness and cohesiveness of pidan white without glucose
      treatment were more retained but showed a decrease in adhesiveness as storage
      time increased up to week 12 (P < 0.05). Higher browning intensity and a*-value
      were noticeable in the pidan white treated with glucose at both levels as the
      storage time increased (P < 0.05). Thus, glucose could enhance the development of
      brown colour, mainly via the Maillard reaction with free amino groups of pidan
      white at alkaline pH, but it could impair the textural property. Pidan white
      without glucose treatment showed the higher color and appearance likeness score,
      but lower texture and odour likeness score than commercial counterpart (P <
      0.05). Therefore, glucose was not a necessary aid for pidan production. 

PMID- 24741168
TI  - Effect of drying and cooking on nutritional value and antioxidant capacity of
      morogo (Amaranthus hybridus) a traditional leafy vegetable grown in South Africa.
AB  - Morogo (vegetables in Tswana) is a green leafy vegetable from the Amaranthaceae
      family that can be harvested from wild growing or cultivated. The objective of
      this study was to determine the nutritional value, the total antioxidant capacity
      and selected bioactive compounds present in morogo leaves, and evaluate the
      effect of drying and cooking. Results showed that morogo contained a significant
      amount of protein (3.6 +/- 0.1 g/100 g FW) and minerals which the level exceed 1%
      of fresh weight. The total antioxidant capacity (MUmole TE/ 100 g FW) determined
      by DPPH and FRAP assays were 118.3 +/- 15.3 and 128.4 +/- 11.9 respectively.
      Total polyphenols (109.4 +/- 7.5 mg GAE/100 g FW), vitamin C (36.6 +/- 1.0 mg
      /100 g FW) and carotenoids represented by beta carotene (25.3 +/- 1.3 mg /100 g
      FW) and xanthophylls (7.48 +/- 0.31 mg /100 g FW) formed a significant part of
      bioactive compounds content of morogo leaves. Since the boiling can cause
      significant losses of compounds in the boiling water, it can be recommended to
      avoid cooking methods that can include a boiling step with discard of boiling
      water. 

PMID- 24741169
TI  - Modified method for preparation of Halubai-an Indian traditional sweet.
AB  - Halubai, a traditional Indian sweet is conventionally prepared by soaking and
      grinding whole cereals/millets to a fine paste, straining it through a cloth and
      cooking the resultant dispersion until it starts gelatinizing. Cooking is
      continued further with the addition of jaggery water, stirring constantly with
      intermittent addition of ghee. This process involves many unit operations, which
      are energy and time consuming. Hence a modified method was developed which is
      energy efficient and time saving without compromising the quality of the product.
      One fine fraction (200 mesh, BS) of cereal/millet flours were used in modified
      method instead of whole cereals. Sensory and instrumental analysis of the samples
      showed that quality of Halubai prepared using modified method was comparable to
      that of samples from conventional method. Correlation studies on sensory data of
      Halubai showed positive relation for the set (r = 0.94) and smoothness (r =
      0.84); and negative relation for stickiness (r = -0.94) with the overall quality.
      Modified method of Halubai preparation which was simple and energy efficient,
      resulted in products with good sensory quality. 

PMID- 24741170
TI  - Detection of collagen through FTIR and HPLC from the body and foot of Donax
      cuneatus Linnaeus, 1758.
AB  - To make more effective use of available marine resources, acid soluble collagen
      (ASC) was isolated from body and foot of wedge clam Donax cuneatus Linnaeus, 1758
      with acetic acid and was characterized for their potential and commercial
      applications. The yield of ASC was 17% and 23% respectively. SDS PAGE, UV and
      FTIR spectroscopy showed that both were type I mainly with slight differences.
      HPLC was used for identifying the presence of different types of amino acids,
      where glycine was more or less 20% in both the samples and takes the lead amino
      acid position and presence of imino acids (11.8 and 12.6%) has been the
      characteristic feature of type I collagen. 

PMID- 24741171
TI  - Nutrients, antinutrients & bioaccessible mineral content (invitro) of pearl
      millet as influenced by milling.
AB  - Pearl millet is an underutilized grain crop commonly used as whole flour for
      traditional food preparation and hence confined to traditional consumers and to
      people of lower economic strata. In this study two commercially available pearl
      millet varieties (Kalukombu & MRB) obtained from the local market were milled
      into whole flour, semi refined flour & bran rich fraction. These milling
      fractions were evaluated for nutrients, antinutrients and mineral
      bioaccessibility. The bran rich fraction, a by product of flour milling contained
      significantly (P <= 0.05) higher ash content (3.3 & 3.5 g/100 g in K & MRB
      respectively). Minerals like phosphorus, calcium and antinutrients like oxalates,
      phytates, were found mainly distributed in the bran fraction. The nutrient
      content of semi-refined flour was comparable to whole flour except for the fat
      content (1.3%). Due to partial separation of the bran fraction, semi refined
      flour was low in antinutrients which improved its mineral bioaccessibility making
      it nutritionally superior. 

PMID- 24741172
TI  - Storage studies on mustard oil blends.
AB  - Mustard oil blends were investigated for fatty acid composition and oxidative
      stability during storage for 3 months at room temperature (15  degrees C to 35 
      degrees C). The blends were prepared using raw mustard oil with selected refined
      vegetable oils namely; palm, safflower, soybean, rice bran, sunflower and sesame
      oil (raw). The fatty acid compositions of all these blends were studied using
      GLC. The developed blends were found to obey the ideal fatty acid ratio as laid
      down by health agencies i.e. 1:2:1:: SFA:MUFA:PUFA. The oxidative stability of
      blends was studied by measuring peroxide value (PV), Kries and Thiobarbituric
      acid (TBA) test. Blends MPSu (mustard oil, palm oil and sunflower oil), MPT
      (mustard oil, palm oil and sesame oil) and MPGr (mustard oil, palm oil and
      groundnut oil) were more stable than other blends during storage. The presence of
      mustard oil in all blends might make them a healthier option for many consumers
      as it is a rich source of omega-3 fatty acids and has anti-carcinogenic
      properties. 

PMID- 24741173
TI  - Value addition of Palmyra palm and studies on the storage life.
AB  - Palmyra palm (Borassus flabellifer L.) belonging to the family Palmae is referred
      to as tree of life with several uses including food, beverage, fibre, medicinal
      and timber. Unfortunately, the nutritionally enriched pulp of ripened palm has
      limited commercial use. Extraction of pulp has been accomplished by using water
      and heat to ensure maximum pulp recovery. Different recipes were tried for the
      preparation of two uncommon value added products like palm spread and palm
      toffee. On the basis of biochemical composition, organoleptic scores, microbial
      estimation and storage study both under ambient and refrigerated conditions; the
      suitable recipe was selected with the maximum acceptability. Gradual increase in
      total soluble solid (TSS), total sugar and reducing sugar while decrease in
      ascorbic acid, pH, beta-carotene and protein content of processed products have
      been observed irrespective of storage condition. The results obtained from
      sensory evaluation and microbial status revealed that palm spread and toffee
      remained acceptable up to 9 months and 8 months, respectively at ambient
      temperature. The income per rupee investment for these two products was found to
      be remunerative. 

PMID- 24741174
TI  - Beneficial dietary effect of turmeric and sulphur on weight gain, fat deposition
      and lipid profile of serum and liver in rats.
AB  - This study was designed to investigate the effects of turmeric powder and
      processed sulphur on the weight gain, body fat deposition and lipid profile of
      serum and liver in Wistar rats. Twenty-five rats of 6 weeks old were divided into
      five groups with 5 rats in each group. Each group was fed different diets as
      follows I. common diet (CON); II. high fat diet (HFD); III. 10% turmeric powder
      with HFD (T); IV. 10% turmeric powder and 0.19% processed sulphur with HFD (TS);
      and V. 0.38% processed sulphur with HFD (S). The experimental feeding was
      continued for 6 weeks. The body weight gain and feed efficiency ratio (FER) in
      the T and TS group rats were significantly (p < 0.05) lower than that of the HFD
      group rats. The retroperitoneal fat weights in the rats belong to T, TS and S
      groups were lower than that of the HFD group rats and the TS group had
      significant (p < 0.05) reduction in retroperitoneal fat compared to the HFD group
      rats. The epididymal fat weights in rats of the T, TS and S groups also showed a
      lowering tendency compared to that of the HFD group rats. The hepatic total lipid
      levels in the T and TS group rats were significantly (p < 0.05) lower than that
      of the HFD group rats. The hepatic triglyceride level in the rats of TS group was
      significantly (p < 0.05) lower than that of the HFD group rats. The serum total
      cholesterol, high-density lipoprotein (HDL) and low density lipoprotein (LDL)
      associated cholesterol contents in rats of the T and TS group were significantly
      (p < 0.05) higher than that of the HFD group rats, however, there was no
      significant difference in serum triglyceride. The results suggest that turmeric
      powder along with sulphur can reduce the weight gain, body fat deposition and
      improve serum and liver lipid profile in rats fed with a high fat diet. 

PMID- 24741175
TI  - Modelling with response surface methodology of the effects of egg yolk, egg white
      and sodium carbonate on some textural properties of beef patties.
AB  - This study was accomplished to determine the effects of egg yolk, egg white and
      sodium carbonate on textural properties of beef patties by using Central
      Composite Design of Response Surface Methodology. Meat patties were prepared
      using beef, lamb tail fat and spices. Effects of addition of egg yolk powder (0
      1%), egg white powder (0-1%) and sodium carbonate (0-1%) on textural properties
      were studied by using a texture analyzer. The TPA and cutting force tests were
      measured in the samples. Effects of sodium carbonate were found to be significant
      (P < 0.01) on springiness, hardness and cohesiveness values of beef patties.
      However, effects of egg white and egg yolk on the textural parameters were not
      found significant (P > 0.05). The levels of sodium carbonate up to 0.72% improved
      the textural properties of beef patties. 

PMID- 24741176
TI  - Quality characteristics of gluten free cookies prepared from different flour
      combinations.
AB  - The present investigation was undertaken on the utilization of alternate
      flours/meals (rice (Oryza sativa), maize (Zea mays), sorghum (Sorghum vulgare)
      and pearl millet (Pennisetum glaucum) for the preparation of gluten free cookies
      as compared to conventional wheat (Triticum aestivum) flour cookies. The
      physicochemical parameters, sensory qualities and functional properties of
      flours/cookies were studied and compared with control cookies. The blend of maize
      and pearl millet had best pasting qualities followed by blend of pearl millet and
      sorghum flour. The control cookies showed a higher yield (186.8%) but stronger
      peak force (2.69 kg). The cookies prepared from rice and maize combination had
      highest spread ratio whereas, the lowest spread ratio was observed in rice and
      sorghum combination. The cookies with pearl millet and sorghum flour combination
      had higher fat, protein, ash and calorific values as compared to control cookies.
      The maximum sensory overall acceptability scores were found for cookies prepared
      from combination of pearl millet and sorghum flour followed by rice and sorghum,
      maize and sorghum, rice and maize, maize and pearl millet, rice and pearl millet
      and control cookies. All gluten free cookies had higher nutritional value as
      compared to control cookies and were acceptable by panelists. 

PMID- 24741177
TI  - Antioxidative effects of Brassica juncea and Moringa oliefera prepared by
      different processing methods.
AB  - The effects of different cooking methods (boiling, microwave cooking, frying and
      steaming ) on the antioxidant activity of Brassica juncea (BJ) and Moringa
      oliefera (MO) were assessed by measuring the total phenolic contents (TPC), total
      flavonoid content (TFC), DPPH radical scavenging activity and Fe(2+)-chelating
      ability . TPC (mg gallic acid equivalents per 100 g of dry weight) and TFC
      (quercetin equivalents per gram of extract) of the fresh, boiled, microwaved,
      fried and steamed BJ were found to be 23.16, 27.7, 18.7, 35.94, 22.06 and 27.09,
      27.8, 24.5, 36.34, 18.01 respectively. For MO it was found to be 34.6, 31.5,
      31.6, 39.4, 33.72 and 70.84, 58.13, 55.4, 69.5, 52.78. A proportionate variation
      in DPPH radical scavenging activity and Fe(2+)-chelating ability was observed.
      The results of the present investigation showed that all the cooking methods
      affected the antioxidant properties of the vegetables; however, frying exhibited
      less deleterious effects when compared with those of other treatments. Thus an
      appropriate method might be sought for the processing of such vegetables to
      retain their antioxidant components at maximum level. 

PMID- 24741178
TI  - The cumulative ash curve: a best tool to evaluate complete mill performance.
AB  - Slick test is carried out by a flour miller to qualitatively segregate the flour
      from different streams in a roller flour mill. This test is done manually by
      pressing flour samples on tray using thin bladed paddle (the slick) and
      inspecting color or dress of the sample. However, the test is subjective and
      totally depends on human judgment. Cumulative ash curve relates to cumulative
      flour ash content and cumulative flour yield, which could help a flour miller to
      be more precise while selecting flour streams for different needs. In this study,
      cleaning and conditioning of wheat was carried out in the pilot plant of
      International School of Milling Technology (ISMT). Further, roller flour milling
      of wheat was done. Flour from different streams (four breaks, five reductions)
      was collected. Each flour stream was analyzed for ash content using standard AACC
      methods. The analytical values of ash content were used to plot the cumulative
      ash curve. It was found that ash content increased in the break passages from
      first to last break, with exception of first break (ash content 0.71%). An
      increase in percentage of ash was observed in the reduction passages (C1 to C5),
      however, C3 ash (0.76%) was slightly higher than that of C4 (0.65%). Higher yield
      of flour with minimum ash content was obtained from the front reduction passages
      C1 and C2; whereas, the break passages and the tail end reduction passages
      produce less flour with higher ash content. 

PMID- 24741179
TI  - Effect of rate of addition of starter culture on textural characteristics of
      buffalo milk Feta type cheese during ripening.
AB  - The effect of rate of addition of starter culture on textural characteristics of
      buffalo milk Feta type cheese was investigated during ripening period up to two
      months. The textural characteristics of buffalo milk Feta type cheese in terms of
      hardness, cohesiveness, springiness, gumminess and chewiness were analyzed by
      using textural profile analyzer. The maximum hardness was found with cheese made
      using 1% culture, while the minimum was found with 2% culture. The cohesiveness
      and springiness decreased as the level of addition of starter culture increased.
      The chewiness of cheese also decreased, as the rate of addition of starter
      culture increased for cheese making. In addition to this, yield, moisture, fat,
      FDM, protein, salt and S/M of fresh buffalo milk Feta type cheese increased with
      the increase in rate of addition of starter culture; however, TS of experimental
      cheeses decreased. 

PMID- 24741180
TI  - Quantitative determination of melatonin in milk by LC-MS/MS.
AB  - A rapid, reliable and sensitive LC-MS/MS method for the determination of
      melatonin in milk was developed and validated. Sample was extracted with
      dichloromethane and cleaned by passing through Chem Elut solid phase extraction
      cartridge. The solvent was evaporated to dryness, reconstituted with methanol and
      analysed by LC-MS/MS on Agilent zorbax Eclipse XDB C-18 rapid resolution
      analytical column. The analytical procedure was found to be accurate, precise and
      linear. The method accuracy was 92.2 % (range 90.06-94.58) and the mean precision
      was 1.55 % and the calibration was linear for 1 to 150 pg mL(-1) (R(2) > 0.99),
      the lowest limit of quantification (LLOQ) was 1 pg mL(-1). 7-D Melatonin (7-DM)
      was used as an internal standard. This method was proved to be a promising method
      for the determination of melatonin for market milk and human milk samples. 

PMID- 24741181
TI  - Drying characteristics of paddy in an integrated dryer.
AB  - Drying characteristics of paddy (long grain variety PR-118 procured from PAU,
      Ludhiana) in an integrated dryer using single as well as combined heating source
      was studied at different air temperatures. The integrated dryer comprises three
      different air heating sources such as solar, biomass and electrical. Drying of
      paddy occurred in falling rate period. It was observed that duration of drying of
      paddy from 22 to 13 % moisture content (w.b.) was 5-9 h depending upon the source
      of energy used. In order to select a suitable drying curve, six thin layer-drying
      models (Newton, Page, Modified Page, Henderson and Pabis, Logarithmic and Wang
      and Singh) were fitted to the experimental moisture ratio data. Among the
      mathematical models investigated, Wang and Singh model best described the drying
      behaviour of paddy using solar, biomass and combined heating sources with highest
      coefficient of determination (r (2)) values and least chi-square, chi (2), mean
      bias error (MBE) and root mean square error (RMSE) values. However, Page model
      adequately described the drying behavior of paddy using electrical heating
      source. 

PMID- 24741182
TI  - Clinical trials for children: some concerns.

PMID- 24741183
TI  - Protective effect of ketamine against hemorrhagic cystitis in rats receiving
      ifosfamide.
AB  - OBJECTIVE: To investigate the possible protective effect of a single dose of
      ketamine and the synergistic effect between ketamine and 2-mercaptoethane
      sulfonate (mesna) against ifosfamide-induced hemorrhagic cystitis. MATERIALS AND
      METHODS: 35 adult female wistar rats were divided into five groups and pretreated
      with ketamine at 10 mg/kg and/or mesna 400 mg/kg 30 minutes before
      intraperitoneal injection of IFS (400 mg/kg) or with saline (control group).
      Hemorrhagic cystitis was evaluated 24 hours after IFS injection according to
      bladder wet weight (BWW), and microscopic changes, i.e. edema, hemorrhage,
      cellular infiltration, and urothelial desquamation. The markers of oxidative
      damage including nitric oxide (NO) and malondialdehyde (MDA) levels and the
      expressions of tumor necrosis factor alpha (TNF-alpha), interleukin 1-beta (IL
      1beta), inducible nitric oxide synthase (i-NOS) and endothelial nitric oxide
      synthase (e-NOS) were also assayed in the bladder tissues. RESULTS: Pretreatment
      with ketamine alone or ketamine in combination with mesna reduced the IFS-induced
      increase of BWW (58,47% and 63,33%, respectively, P < 0.05). IFS- induced
      microscopic alterations were also prevented by ketamine with or without mesna (P
      < 0.05). In addition, also statistically insignificant, the bladder tissue
      expressions of IL-1beta were lower in ketamine and/or mesna-receiving groups (P >
      0,05). The parameters of oxidative stress, the NO and the MDA contents of the
      bladder tissues of the study groups were not different. CONCLUSION: The results
      of the present study suggest that a single dose of ketamine pretreatment
      attenuates experimental IFS-induced bladder damage. It is therefore necessary to
      investigate ketamine locally and systematically with various dosing schedules in
      order to reduce the bladder damage secondary to oxazaphosphorine-alkylating
      agents and these results may widen the spectrum of ketamine.

PMID- 24741184
TI  - A study of potential drug-drug interactions among hospitalized cardiac patients
      in a teaching hospital in Western Nepal.
AB  - AIM: Drug-drug interaction (DDI) is of major concern in patients with complex
      therapeutic regimens. The involvement of cardiovascular medicines in drug
      interaction is even higher. However, reports of DDI between these groups of drugs
      are few. The study aims to identify the potential DDI among hospitalized cardiac
      patients. Furthermore, we assessed the possible risk factors associated with
      these interactions. SUBJECTS AND METHODS: The Type of study prospective
      observational study was conducted from May 2012 to August 2012 among hospitalized
      cardiac patients. Cardiac patients who were taking at least two drugs and who had
      a hospital stay of at least 24 h were enrolled. The medications of the patients
      were analyzed for possible interactions using the standard drug interaction
      database - Micromedex -2 (Thomson Reuters) * 2.0. RESULTS: From a total of 150
      enrolled patients, at least one interacting drug combination was identified among
      32 patients. The incidence of potential DDI was 21.3%. A total of 48 potentially
      hazardous drug interactions were identified. Atorvastatin/azithromycin (10.4%),
      enalapril/metformin (10.4%), enalapril/potassium chloride (10.4%),
      atorvastatin/clarithromycin (8.3%) and furosemide/gentamicin (6.3%) were the most
      common interacting pairs. Drugs most commonly involved were atorvastatin,
      enalapril, digoxin, furosemide, clopidogrel and warfarin. Majority of
      interactions were of moderate severity (62.5%) and pharmacokinetic (58.3%) in
      nature. Increased number of medicines, prolonged hospital stays and comorbid
      conditions were the risk factors found associated with the potential DDI.
      CONCLUSIONS: This study highlighted the need of intense monitoring of patients
      who have identified risk factors to help detect and prevent them from serious
      health hazards associated with drug interactions.

PMID- 24741185
TI  - Effects of delayed puerarin treatment in long-term neurological outcomes of focal
      ischemic stroke in rats.
AB  - OBJECTIVE: The present study aimed at investigate the therapeutic effects of
      delayed puerarin treatment in neurological outcomes after middle cerebral artery
      occlusion (MCAO) in rats. MATERIALS AND METHODS: Male Wistar rats were subjected
      to MCAO for 120 min followed by reperfusion for 14 days. Puerarin (0, 50, 100,
      200 mg/kg, intra-peritoneally) was administered at 24 h after stroke onset and
      repeated daily for 14 days. Neurological deficits were evaluated at 1, 4, 7, 14
      days after stroke. Brain infarct volume and peri-infarct context vessel density
      were examined at 14 days after stroke. RESULTS: Puerarin significantly improved
      neurological functions up to 14 days after stroke and decreased the infarct
      volume with doses of 50 mg/kg and 100 mg/kg compared with saline controls.
      Puerarin treatment also significantly increased peri-infarct context vessel
      density at 14 days after stroke. CONCLUSIONS: Delayed treatment of puerarin
      initiated at 24 h after stroke is beneficial with improved long-term neurological
      outcomes and reduced infarction volume in focal ischemic stroke in rats. Enhanced
      vascular remodeling by puerarin might at least partially contribute to its
      beneficial effects.

PMID- 24741186
TI  - Mechanism of testicular protection of carvedilol in streptozotocin-induced
      diabetic rats.
AB  - AIMS: Male sub-fertility and infertility are major complications of diabetes
      mellitus. The non-selective beta-blocker carvedilol has been reported to have
      favorable effects on some of the diabetic complications based on its antioxidant
      and anti-apoptotic effects. This study aims to evaluate the possible testicular
      protective effect of carvedilol in streptozotocin (STZ)-induced diabetic rat
      model and its possible mechanisms. MATERIALS AND METHODS: Diabetes was induced by
      a single i.p. dose of 65 mg/kg of STZ. In parallel groups of diabetic rats,
      carvedilol in low and high doses (1 and 10 mg/kg/day orally) were administered
      for 4 weeks. Oxidative stress markers as reduced glutathione (GSH) and the
      product of lipid peroxidation; malondialdehyde (MDA) were evaluated in testicular
      homogenate. The level of expression of the apoptotic marker; caspase 3, was
      assessed using western blot, followed by densitometric analysis. RESULTS:
      Induction of diabetes caused distortion of histological normal testicular
      structure, with decrease (P < 0.05) in GSH and increase (P < 0.05) in MDA, as
      well as induction of caspase 3 expression. Carvedilol in low or high doses
      reverted diabetes-induced histological damage, restored antioxidant activity and
      ameliorated caspase 3 expression. CONCLUSION: Carvedilol confers testicular
      protection against diabetes-induced damage through antioxidant and anti-apoptotic
      mechanisms.

PMID- 24741187
TI  - Mentha piperita in nephrotoxicity--a possible intervention to ameliorate renal
      derangements associated with gentamicin.
AB  - OBJECTIVE: Free radical generation has a strong role in the pathogenesis of renal
      damage associated with the use of gentamicin. Therefore, the present study was
      carried out to evaluate the renoprotective effect of Mentha piperita against
      gentamicin induced nephrotoxicity. MATERIALS AND METHODS: A total of 24 male
      rabbits were divided into 4 groups receiving normal saline, gentamicin, M.
      piperita extract and co-therapy of extract and gentamicin respectively.
      Gentamicin was provided as 80 mg/kg/day intramuscularly and extract was given 200
      mg/kg/day orally for a period of 21 days. Serum and urinary biochemical
      parameters and histological changes were studied for each group. The impact of
      the extract on the antibacterial action of gentamicin was also evaluated.
      RESULTS: Animals treated with gentamicin showed derangements in serum and urinary
      biochemical parameters. These alterations were reversed by treatment with M.
      piperita extract. The histological changes showed in gentamicin group were also
      reverted by treatment with the extract. Further the plant did not influence the
      efficacy of gentamicin with respect to its antimicrobial properties. CONCLUSION:
      Co-therapy of M. piperita with gentamicin successfully attenuated biochemical
      kidney functioning derangements and morphological changes associated with
      gentamicin.

PMID- 24741188
TI  - Evaluation of aqueous extract of Murraya koenigii in unilateral renal ischemia
      reperfusion injury in rats.
AB  - AIM: The aqueous extract of leaves of Murraya koenigii was studied for its
      renoprotective potential against unilateral renal ischemia reperfusion (RIR)
      injury in male Wistar rats. MATERIALS AND METHODS: Healthy adult male Wistar rats
      were divided into five groups (n = 8) and were treated with 200 mg/kg., p.o. of
      aqueous extract of M. koenigii (AEMK) for 30 days to assess both preventive and
      curative effects of AEMK. Except Group I, RIR was induced to all the groups by
      clamping the left renal artery using artery clamp for 1 h followed by reperfusion
      by removing the clamp. Groups II and III underwent RIR at 30(th) day whereas RIR
      was induced in Groups IV and V at 1(st) day of treatment schedule. Biochemical
      parameters (serum creatinine, blood urea nitrogen, serum total protein and serum
      Na(+)), urinary parameters (urine output, urinary creatinine, urinary urea,
      urinary total protein, urinary Na(+)), in vivo anti-oxidants, renal
      myeloperoxidase (MPO) activity and histopathology of kidneys were monitored.
      Statistical significance was set at P < 0.05. RESULTS: Rats were treated with
      AEMK significantly (P < 0.05) restored the serum and urinary parameters with
      significant (P < 0.05) improvement in endogenous anti-oxidants such as superoxide
      dismutase, catalase and reduced glutathione and decreased levels of
      malondialdehyde and renal MPO when compared with the control groups.
      Histopathological examination also supported the biochemical and urinary tests.
      CONCLUSIONS: Aqueous extract of M. koenigii possesses both preventive and
      curative effects against RIR injury.

PMID- 24741189
TI  - Neuroprotective effect of Tinospora cordifolia ethanol extract on 6-hydroxy
      dopamine induced Parkinsonism.
AB  - OBJECTIVE: The present study investigates the neuroprotective activity of ethanol
      extract of Tinospora cordifolia aerial parts against 6-hydroxy dopamine (6-OHDA)
      lesion rat model of Parkinson's disease (PD). MATERIALS AND METHODS: T.
      cordifolia ethanol extract (TCEE) was standardized with high performance thin
      layer chromatography using berberine. Experimental PD was induced by
      intracerebral injection of 6-OHDA (8 MUg). Animals were divided into five groups:
      sham operated, negative control, positive control (levodopa 6 mg/kg) and two
      experimental groups (n = 6/group). Experimental groups received 200 and 400 mg/kg
      of TCEE once daily for 30 days by oral gavage. Biochemical parameters including
      dopamine level, oxidative stress, complex I activity and brain iron asymmetry
      ratio and locomotor activity including skeletal muscle co-ordination and degree
      of catatonia were assessed. RESULTS: TCEE exhibited significant neuroprotection
      by increasing the dopamine levels (1.96 +/- 0.20 and 2.45 +/- 0.40 ng/mg of
      protein) and complex I activity (77.14 +/- 0.89 and 78.50 +/- 0.96 nmol/min/mg of
      protein) at 200 and 400 mg/kg respectively when compared with negative control
      group. Iron asymmetry ratio was also significantly attenuated by TCEE at 200
      (1.57 +/- 0.18) and 400 mg/kg (1.11 +/- 0.15) when compared with negative control
      group. Neuroprotection by TCEE was further supported by reduced oxidative stress
      and restored locomotor activity in treatment groups. CONCLUSION: Results show
      that TCEE possess significant neuroprotection in 6-OHDA induced PD by protecting
      dopaminergic neurons and reducing the iron accumulation.

PMID- 24741190
TI  - Hepatotoxicity of Teucrium chamaedrys L. decoction: role of difference in the
      harvesting area and preparation method.
AB  - AIM: Two recurrent cases of severe acute liver injury attributed to the use of a
      wild germander decoction, prepared with some variation in traditional method has
      been reported. The aim of the present study was to correlate the hepatotoxic
      effect observed in patients who consumed germander decoction with teucrin A
      levels. Antioxidant properties were analyzed to assess any possible differences
      between the decoction used traditionally by the family (without negative
      consequences) and the decoction taken by the patients. MATERIALS AND METHODS:
      Different types of germander decoctions were prepared in the laboratory by
      simulating the same conditions for preparing the decoction by the patients and
      their family members. The levels of teucrin A, the polyphenols and the
      antioxidant power were determined. One-way analysis of variance was used to test
      for differences between the groups. RESULTS AND CONCLUSIONS: The extract consumed
      by the patients had higher concentration of teucrin A, lower antioxidant activity
      and lower content of polyphenols compared with the traditional decoction,
      revealing an inverse relationship between teucrin A content and antioxidant
      capacity. These case reports emphasize that more information is needed on the
      safety and quality of these natural products.

PMID- 24741191
TI  - An evaluation of vardenafil as a calcium channel blocker in pulmonary artery in
      rats.
AB  - OBJECTIVE: Vardenafil was reported to relax rat pulmonary artery through
      endothelium-dependent mechanisms. The aim of this in vitro study was to
      investigate other related mechanisms for this effect. MATERIALS AND METHODS:
      Endothelium-intact and denuded artery rings were suspended in order to record
      isometric tension. In the rings with or without endothelium, the concentration
      response curves for vardenafil were generated. In the rings without endothelium
      the contractile response induced by phenylephrine (Phe) or KCl was assessed in
      the presence or absence of vardenafil. In the last set of experiments, pulmonary
      artery rings were exposed to calcium-free isotonic depolarizing solution and the
      contractile response induced by the addition of calcium was evaluated in the
      presence or absence of vardenafil, nifedipine, verapamil or 1H-[1,2,4]
      oxadiazolo[4,3-a] quinoxalin-1-one (ODQ). RESULTS: Vardenafil attenuated
      pulmonary artery contraction induced by phenylephrine in the presence and absence
      of endothelium. In addition, vardenafil attenuated both Phe or KCl-induced
      contraction but, it's effect on the KCl dose-response curve was more significant.
      Vardenafil also inhibited the contractile response induced by calcium in a dose
      dependent manner. Addition of nifedipine or verapamil did not significantly alter
      this effect while ODQ incubation significantly inhibited vardenafil-induced
      relaxation. CONCLUSION: From these findings, it was proposed that vardenafil
      relaxed rat pulmonary artery through inhibiting calcium influx.

PMID- 24741192
TI  - Neuropharmacological evaluation of a novel 5-HT3 receptor antagonist (6g) on
      chronic unpredictable mild stress-induced changes in behavioural and brain
      oxidative stress parameters in mice.
AB  - AIM: The aim of the study was to evaluate a novel 5 HT3 receptor antagonist (6g)
      on chronic stress induced changes in behavioural and brain oxidative stress
      parameter in mice. A complicated relationship exists among stressful stimuli,
      body's reaction to stress and the onset of clinical depression. Chronic
      unpredictable stressors can produce a situation similar to human depression, and
      such animal models can be used for the preclinical evaluation of antidepressants.
      MATERIALS AND METHODS: In the present study, a novel and potential 5-HT3 receptor
      antagonist (4-benzylpiperazin-1-yl)(3-methoxyquinoxalin-2-yl) methanone (6g) with
      good Log P (3.08) value and pA 2(7.5) values, synthesized in our laboratory was
      investigated to study the effects on chronic unpredictable mild stress (CUMS)
      induced behavioural and biochemical alterations in mice. Mice were subjected to
      different stress paradigms daily for a period of 28 days to induce depressive
      like behaviour. RESULTS: The results showed that CUMS caused depression-like
      behaviour in mice, as indicated by the significant (P < 0.05) decrease in sucrose
      consumption and locomotor activity and increase in immobility the forced swim
      test. In addition, it was found that lipid peroxidation and nitrite levels were
      significantly (P < 0.05) increased, whereas glutathione levels, superoxide
      dismutase and catalase activities decreased in brain tissue of CUMS-treated mice.
      '6g' (1 and 2 mg/kg, p.o., 21 days) and fluoxetine treatment (20 mg/kg, p.o., 21
      days) significantly (P < 0.05) reversed the CUMS-induced behavioural (increased
      immobility period, reduced sucrose preference and decreased locomotor activity)
      and biochemical (increased lipid peroxidation; decreased glutathione levels,
      superoxide dismutase and catalase activities). However fluoxetine treatment (20
      mg/kg, p.o., 21 days) significantly decreased the nitrite level in the brain
      while '6g' (1 and 2 mg/kg, p.o., 21 days) did not show significant (P < 0.05)
      effect on the nitrite levels in brain. CONCLUSION: Compound '6g' exerted
      antidepressant-like effects in behavioural despair paradigm in chronically
      stressed mice by restoring antioxidant mechanisms.

PMID- 24741193
TI  - Hepatoprotective activity of Tephrosia purpurea against arsenic induced toxicity
      in rats.
AB  - AIM: The present study was conducted to evaluate the hepatoprotective activity of
      Tephrosia purpurea (TP) against sodium arsenite (NaAsO2) induced sub-acute
      toxicity in rats. MATERIALS AND METHODS: Twenty four wistar albino rats of either
      sex were randomly divided into three groups. Group II and III were orally
      administered with sodium arsenite (10 mg/kg) daily in drinking water for 28 days.
      Additionally Group III was orally treated with hydro-alcoholic extract of
      Tephrosia purpurea (TP) @ 500 mg/kg daily for the same time period, whereas only
      deionized water was given to Group I (control). Serum biomarker levels, oxidative
      stress parameters and arsenic concentration were assessed in liver.
      Histopathology was also conducted. RESULTS: It has been seen that TPE (500 mg/kg)
      significantly (P < 0.01) reduced serum ALT, AST, ALP activity and increased total
      protein and reduced necrosis and inflammation in liver of group III compared to
      group II. A significantly (P < 0.01) higher LPO and lower GSH levels without
      change in SOD activity in liver was also observed in group II compared to group
      III, though there was no significant difference in arsenic accumulation between
      them. The plant extract also protects the animals of group III from significant
      (P < 0.01) reduction in body weight. CONCLUSION: Our study shows that
      supplementation of Tephrosia purpurea extract (500 mg/kg) could ameliorate the
      hepatotoxic action of arsenic.

PMID- 24741194
TI  - Population pharmacokinetics of bupivacaine in combined lumbar and sciatic nerve
      block.
AB  - OBJECTIVES: The primary aim of this study was to establish the population
      pharmacokinetic (PPK) model of bupivacaine after combined lumbar plexus and
      sciatic nerve blocks and secondary aim is to assess the effect of patient's
      characteristics including age, body weight and sex on pharmacokinetic parameters.
      MATERIALS AND METHODS: A total of 31 patients scheduled for elective lower
      extremity surgery with combined lumbar and sciatic nerve block using plain
      bupivacaine 0.5% were included. The total bupivacaine plasma concentrations were
      measured before injection and after two blocks placement and at selected time
      points. Monitoring of bupivacaine was made by high performance liquid
      chromatography (HPLC) with ultraviolet detection. Non-linear mixed effects
      modeling was used to analyze the PPK of bupivacaine. RESULTS: One compartment
      model with first order absorption, two input compartments and a central
      elimination was selected. The Shapiro-Wilks test of normality for normalized
      prediction distribution errors for this model (P = 0.156) showed this as a valid
      model. The selected model predicts a population clearance of 930 ml/min (residual
      standard error [RSE] = 15.48%, IC 95% = 930 +/- 282.24) with inter individual
      variability of 75.29%. The central volume of distribution was 134 l (RSE =
      12.76%, IC = 134 +/- 33.51 L) with inter individual variability of 63.40%. The
      absorption of bupivacaine in two sites Ka1 and Ka2 were 0.00462/min for the
      lumbar site and 0.292/min for the sciatic site. Age, body weight and sex have no
      effect on the bupivacaine pharmacokinetics in this studied population.
      CONCLUSION: The developed model helps us to assess the systemic absorption of
      bupivacaine at two injections sites.

PMID- 24741195
TI  - Effect of trapidil in myocardial ischemia-reperfusion injury in rabbit.
AB  - OBJECTIVES: To evaluate the cardioprotective effects of trapidil on myocardial
      ischemia-reperfusion injury (MIRI) in rabbits. MATERIALS AND METHODS: Rabbits
      were subjected to 40 min of myocardial ischemia followed by 120 min of
      reperfusion. Blood for superoxide dismutase (SOD) and malondialdehyde (MDA) were
      estimated. At the end of reperfusion, the rabbits were sacrificed and the hearts
      were isolated for histological examination. An apoptotic index (AI) was
      determined using the terminal deoxynucleotidyl transferase (TdT)-mediated dUTP
      nick-end-labeling (TUNEL) method. The expression of apoptosis-related proteins
      Bax and Bcl-2 was analyzed using immunohistochemistry. Statistical analyses were
      performed by one-way analysis of variance (ANOVA), P < 0.05 considered
      statistically significant. RESULTS: Trapidil caused a significant (P < 0.05)
      increase in SOD activity, as decreased MDA levels and significantly (P < 0.05)
      reduced the expression of Bax as compared with the ischemia-reperfusion (IR)
      control group. CONCLUSION: Trapidil may attenuate the myocardial damage produced
      by IR injury and offer potential cardioprotective action.

PMID- 24741196
TI  - Hepatoprotective and antioxidant activity of N-acetyl cysteine in carbamazepine
      administered rats.
AB  - OBJECTIVES: The present study evaluates the hepatoprotective activity of N-acetyl
      cysteine (NAC) against carbamazepine (CBZ)-induced hepatotoxicity. MATERIALS AND
      METHODS: Rats were treated with CBZ (50 mg/kg p.o.) and CBZ supplemented with NAC
      50, 100 and 200 mg/kg for 45 days, after which blood samples were collected and
      subjected to liver function tests. Animals were killed, liver was separated,
      weighed and the levels of antioxidants and liver enzymes were estimated. In
      addition, histopathological investigation was also performed. RESULTS: Serum
      glutamate pyruvate transaminase (SGPT), serum glutamate oxaloacetate (SGOT)
      transaminase, alkaline phosphatase (ALP), bilirubin, lipid peroxidation, absolute
      and relative liver weights were significantly (P < 0.05) elevated, whereas serum
      levels of albumin, total protein and body weight were decreased in the CBZ
      treated animals. CBZ also produced vacuolar degeneration, centrilobular
      congestion and hepatic necrosis as evidenced from histopathological report. NAC
      significantly reduced the levels of serum transaminase, ALP, bilirubin and liver
      weight and increased the levels of total protein, albumin and body weight.
      CONCLUSION: It was observed that NAC increased the glutathione (GSH) content,
      reduced lipid peroxidation and reversed the CBZ-induced histopathological
      abnormalities. CBZ-induced hepatotoxicity may be due its toxic epoxide metabolite
      induced oxidative stress.

PMID- 24741197
TI  - Anti-fibrosis effects of Huisheng oral solution in CCl4-induced hepatic fibrosis
      in rat.
AB  - AIM: Some gradient of Huisheng oral solution (HOS) has been reported to have anti
      fibrosis activity. This study was designed to investigate whether HOS could
      inhibit liver fibrosis and to elucidate its molecular mechanism of action.
      MATERIALS AND METHODS: Hepatic fibrosis model in rat was induced by subcutaneous
      injection of CCl4. Rats in the treatment group were administrated with HOS
      intragastrically. Hematoxylin and eosin (H and E) staining and Masson's trichrome
      staining were used to examine the changes in liver pathology. Levels of ALT, AST,
      LDH, hyaluronic acid (HA) and laminin (LN) in serum and hydroxyproline (Hyp) in
      liver were detected by biochemical examination and radioimmunoassay,
      respectively. The expression and distribution of Smad3, TGF-beta1, alpha-SMA and
      TIMP-1 were observed and the active TGF-beta1 was tested. RESULTS: Our data
      demonstrated that HOS alleviated CCl4-induced collagen deposition in liver
      tissue, improved liver condition and liver function in rats. HOS also
      significantly reduced the expression and distribution of Smad3, TGF-beta1, alpha
      SMA and TIMP-1 as well as decreased active TGF-beta1. CONCLUSIONS: This study
      revealed that HOS attenuates the development of liver fibrosis through
      suppressing the TGF-beta1 pathway. It provides us a new approach to treatment of
      liver fibrosis.

PMID- 24741198
TI  - Variation of adverse drug reaction profile of platinum-based chemotherapy with
      body mass index in patients with solid tumors: an observational study.
AB  - OBJECTIVES: Toxicity of cancer chemotherapy may be affected by nutritional status
      of patients which is reflected in the body mass index (BMI). We sought to assess
      whether the adverse drug reaction (ADR) profile of platinum-based chemotherapy
      varies with BMI status. MATERIALS AND METHODS: Adult patients of either sex,
      suffering from a solid tumor (lung, head and neck, ovary, gall bladder, stomach,
      colon) and started on platinum-based chemotherapy as initial treatment were
      included. BMI at chemotherapy commencement was obtained from medical records.
      Events were recorded and graded as per Eastern Co-operative Oncology Group Common
      Toxicity Criteria-patients' complaints; clinically evident signs and laboratory
      reports were considered. Frequencies of individual adverse events were compared
      between low BMI (<18.5 kg/m(2)) and satisfactory BMI groups. Similar comparisons
      were done for events with grades 2 or 3 severities. RESULTS: A total of 50
      patients were observed over a 3-month period of whom 17 (34%) belonged to the low
      BMI group. Nausea, vomiting, diarrhea, stomatitis, anemia, alopecia, tinnitus and
      paresthesia were the commonly observed ADRs. The frequencies of anemia (P =
      0.152) and vomiting (P = 0.140) and severity of grades of nausea (P = 0.066),
      anemia (P = 0.120) and paresthesia (P = 0.128) showed a higher trend in the low
      BMI group though differences were not statistically significant. The frequencies
      of tinnitus (P = 0.021) and paresthesia overall (P = 0.036) were significantly
      higher in the low BMI group. CONCLUSION: ADR profile of primary platinum-based
      chemotherapy appears to be partly influenced by BMI. This suggests the importance
      of maintaining adequate nutrition in patients and the need for greater vigilance
      in those with low BMI.

PMID- 24741199
TI  - Docetaxel-induced palmoplantar erythrodysesthesia syndrome and long-lasting
      multiple nail changes.
AB  - Palmoplantar erythrodysesthesia syndrome (PPES) and nail changes are common
      presentations of cutaneous toxicity of docetaxel chemotherapy, which deteriorate
      the quality of life of patients. Herein, we describe a female patient who
      developed PPES and multiple nail changes due to docetaxel treatment for
      infiltrative ductal carcinoma. Cold application and elevation of extremities
      during docetaxel infusion, potent topical steroids and oral pyridoxine increased
      the tolerance to chemotherapy and provided regression of painful cutaneous
      lesions without cessation of the treatment. 

PMID- 24741200
TI  - Lorazepam-induced diplopia.
AB  - Diplopia - seeing double - is a symptom with many potential causes, both
      neurological and ophthalmological. Benzodiazepine induced ocular side-effects are
      rarely reported. Lorazepam is one of the commonly used benzodiazepine in
      psychiatric practice. Visual problems associated with administration of lorazepam
      are rarely reported and the frequency of occurrence is not established. We report
      a rare case of lorazepam-induced diplopia in a newly diagnosed case of obsessive
      compulsive disorder. 

PMID- 24741201
TI  - Delayed onset renal failure in a patient on tenofovir based antiretroviral
      regimen.
AB  - Tenofovir is recommended as one of the first line agents in combination with
      other antiretroviral drugs for management of human immunodeficiency virus (HIV).
      It is known to cause renal failure after exposure for a median duration of 5
      months. We report tenofovir induced adverse drug reaction in a 56-year-old female
      patient who was diagnosed to have HIV 1 infection since 10 years. The combination
      antiretroviral treatment included tenofovir, emtricitabine and
      ritonavir/lopinavir regimen since the last 6 years. She presented with recent
      onset renal failure and renal biopsy showed interstitial nephritis which could
      probably attributable to tenofovir. 

PMID- 24741202
TI  - Acute generalized exanthematous pustulosis induced by piroxicam: a case report.
AB  - Acute generalized exanthematous pustulosis (AGEP) is a severe adverse cutaneous
      reaction characterized by an acute episode of sterile pustules over erythematous
      edematous skin. The main triggering drugs are antibiotics, mainly beta-lactam and
      macrolides. Non-steroid anti-inflammatory drugs may rarely be responsible. We
      describe a case of a woman with AGEP, who presented with generalized pustulosis
      lesions after the use of piroxicam for renal colic. The diagnosis was confirmed
      by the clinical and histological correlations and the dermatosis resolved after
      withdrawal of the drug. 

PMID- 24741203
TI  - Anaphylaxis following intravenous ranitidine: a rare adverse reaction of a common
      drug.
AB  - Ranitidine hydrochloride is a widely used drug that is generally well-tolerated.
      Anaphylaxis is rarely observed with ranitidine. We report a case who developed
      severe anaphylaxis following single dose of intravenous ranitidine. The article
      highlights the importance of recognition of this serious adverse event and re
      emphasizes the need for cautious use of drugs, especially in those with known
      history of allergy. 

PMID- 24741204
TI  - Transparent Conductive Two-Dimensional Titanium Carbide Epitaxial Thin Films.
AB  - Since the discovery of graphene, the quest for two-dimensional (2D) materials has
      intensified greatly. Recently, a new family of 2D transition metal carbides and
      carbonitrides (MXenes) was discovered that is both conducting and hydrophilic, an
      uncommon combination. To date MXenes have been produced as powders, flakes, and
      colloidal solutions. Herein, we report on the fabrication of ~1 * 1 cm2 Ti3C2
      films by selective etching of Al, from sputter-deposited epitaxial Ti3AlC2 films,
      in aqueous HF or NH4HF2. Films that were about 19 nm thick, etched with NH4HF2,
      transmit ~90% of the light in the visible-to-infrared range and exhibit metallic
      conductivity down to ~100 K. Below 100 K, the films' resistivity increases with
      decreasing temperature and they exhibit negative magnetoresistance-both
      observations consistent with a weak localization phenomenon characteristic of
      many 2D defective solids. This advance opens the door for the use of MXenes in
      electronic, photonic, and sensing applications.

PMID- 24741205
TI  - Minimal access surgery in Pediatric Surgery.

PMID- 24741206
TI  - Day case laparoscopic cholecystectomy in children: A review of 11 cases.
AB  - AIM: The aim of this paper is to study the outcome of day case laparoscopic
      cholecystectomy (DCLC) in children. MATERIALS AND METHODS: A clinical pathway for
      day care laparoscopic cholecystectomy was followed with emphasis on the
      analgesia, post-operative nausea and vomiting (PONV), feeding, mobilization, pain
      scoring and patient satisfaction. Demographic and clinical data were recorded
      prospectively from March 2013 to November 2013. The setup allowed easy access to
      an overnight stay if needed. Hospital stay, complications, the need for medical
      advice after discharge, convalescence and patients satisfaction were analyzed.
      RESULTS: We admitted 11 children with symptomatic cholelithiasis for day case
      laparoscopic surgery. There were no intra- or post-operative complications. The
      incidence of PONV was 0/11. There was no readmission. 4/11 patients complained of
      shoulder tip pain on follow-up next day. There was no overnight stay.
      CONCLUSIONS: Adoption of a DCLC pathway is feasible and safe for children.
      Emphasis on adequate pain management and avoidance of PONV results in a high rate
      of day case surgery equivalent to that achieved in adult practice.

PMID- 24741207
TI  - Ovarian preservation in children for adenexal pathology, current trends in
      laparoscopic management and our experience.
AB  - AIMS: Primary cysts and tumors of the ovary alongwith torsion are often regarded
      as an indication for open oophorectomy because of the fear of leaving an ischemic
      organ inside and chances of recurrence. We wish to report our experience of both
      modalities of management where we initially removed adenexal torsion by either
      laparoscopic salpingo-oophorectomy or oophorectomy, but later followed a more
      conservative approach of adenexal lesion removal with ovarian preservation.
      MATERIALS AND METHODS: Retrospective review of clinical records of patients with
      ovarian pathology who were managed laparoscopically. RESULTS: 46 cases of
      pediatric ovarian pathology were managed between March 2006 and March 2013 in two
      centers by a team of surgeons. The age ranged from 1 days to 18 years (average
      14.3 years) and the pathology varied from 30 cases of a simple ovarian cyst with
      torsion, 3 cases of ovarian torsion without any cyst, 7 cases of a dermoid cyst
      with torsion in all, 1 case of secreting ovarian tumor and 5 cases of a
      paraovarian cyst with torsion. All patients had a normal tumor marker except 1
      girl with a functional ovarian tumor who had elevated LDH and estrogen levels
      alongwith suppressed LH and FSH. In the initial period of our study we did 1
      salpingo-oophorectomy for a suspected complex lesion and two oophorectomies for
      torsion with a simple cyst. In the later part of our study we performed
      laparoscopic cystectomy and ovarian preservation in 40 cases, including 7 cases
      of dermoid, where we performed laparoscopic detorsion with dermoid cystectomy and
      ovarian preservation in the same sitting. In three cases of chronic torsion who
      presented to us late, we could not preserve the ovary and had to resort to
      salpingo-ophorectomy. Histology showed a simple corpus luteal and follicular
      ovarian cyst in 31 cases, a paraovarian cyst in 5 cases with mature teratoma in 7
      cases. Twenty-five patients with ovarian preservation following detorsion were
      subjected to follow-up ultrasound, who were found to have normal shape, size and
      blood flow compared to the contra lateral side. CONCLUSION: We outline our
      experience from the management of 46 cases of various ovarian pathologies with
      and without ischemia and found that ovarian torsion with a benign pathology and
      ischemia is not a contraindication for ovarian preservation, as pointed out in
      the current literature.

PMID- 24741208
TI  - Laparoscopic-assisted transanal pull-through for Hirschsprung's disease:
      Comparison between partial and near total laparoscopic mobilization of rectum.
AB  - BACKGROUND: Transanal pull-through with laparoscopic assistance is gaining
      popularity. How much rectal dissection to do laparoscopically and how much
      transanally is not clear. Laparoscopic rectal mobilization is akin to open pelvic
      dissection of Swenson's operation - the most physiological procedure. Through
      this comparative study, we aim to evolve a technique that maximizes the benefits
      of Swenson's technique and minimizes the problems of a transanal procedure.
      MATERIALS AND METHODS: Twenty patients (19 boys and one girl, newborn to 6 years)
      with Hirschsprung's disease (HD) were randomized for laparoscopic-assisted
      transanal pull-through (LATAPT) either by near complete (Group A) or partial
      (Group B) laparoscopic mobilization of rectum. Patients were followed up for at
      least 3 months. Demographic profile; operative details (time taken, blood loss,
      operative difficulty, and complications); postoperative course (duration of
      urinary catheter, oral feeding, and hospital stay); and follow-up stooling
      pattern, consistency, and continence were compared in the two groups. RESULTS:
      The time taken for laparoscopic mobilization was marginally higher in group A,
      but the time taken for transanal dissection in this group was significantly less
      than in group B. All other comparisons showed no significant difference in the
      two groups. Stool frequency and continence improved with time in both groups.
      CONCLUSION: Extent of laparoscopic mobilization of rectum does not appear to be a
      factor deciding the outcomes. No recommendations could be made in view of the
      small number of cases. However, it shows that laparoscopic assistance can be used
      to maximize the benefits of Swenson type of operation and a transanal pull
      through.

PMID- 24741209
TI  - Laparoscopic repair of hernia in children: Comparison between ligation and
      nonligation of sac.
AB  - AIM: The essence of the current techniques of laparoscopic hernia repair in
      children is suture ligation of the neck of the hernia sac at the deep ring with
      or without its transection. Some studies show that during open hernia repair,
      after transection at the neck it can be left unsutured without any consequence.
      This study was aimed to see if the same holds true for laparoscopic hernia
      repair. MATERIALS AND METHODS: Sixty patients (52 boys and eight girls, 12-144
      months) with indirect inguinal hernia were randomized for laparoscopic repair
      either by transection of the sac alone (Group I) or transection plus suture
      ligation of sac at the neck (Group II). Outcome was assessed in terms of time
      taken for surgery, recurrence, and other complications. RESULT: Thirty-eight
      hernia units in 28 patients were repaired by transection alone (Group I) and 34
      hernia units in 29 patients were repaired by transection and suture ligation
      (Group II). Three patients were found to have no hernia on laparoscopy.
      Recurrence rate and other complications were not significantly different in the
      two groups. All recurrences occurred in hernias with ring size more than 10 mm.
      CONCLUSION: Laparoscopic repair of hernia by circumferential incision of the
      peritoneum at the deep ring is as effective as incision plus ligation of the sac.

PMID- 24741210
TI  - Portal hypertension: A critical appraisal of shunt procedures with emphasis on
      distal splenorenal shunt in children.
AB  - BACKGROUND: Extrahepatic portal venous obstruction (EHPVO) is the most common
      cause of pediatric portal hypertension. We analyzed the investigative protocol
      and results of portosystemic shunts in this group of patients. MATERIALS AND
      METHODS: A total of 40 consecutive children aged below 12 years operated with a
      diagnosis of extra-hepatic portal hypertension formed the study group. Historical
      data and clinical data were collected. All patients underwent upper
      gastrointestinal endoscopy, ultrasound Doppler and computed tomographic portogram
      pre-operatively and post-operatively. Results with respect to shunt patency,
      hypersplenism and efficacy of different radiological investigations were
      collected. RESULTS: A total of 40 patients, 28 boys and 12 girls constituted the
      study group. Lienorenal shunt (LRS) was performed in 14 patients; distal
      splenorenal shunt in 21 patients and side-to-side lienorenal shunt in 4 patients,
      inferior mesenteric renal shunt was performed in 1 patient. Follow-up ranged from
      36 to 70 months. At a minimum follow-up of 3 years, 32 (80%) patients were found
      to have patent shunts. Patent shunts could be visualized in 30/32 patients with
      computer tomographic portogram (CTP) and 28/32 with ultrasound. Varices regressed
      completely in 26/32 patients and in the rest incomplete regression was seen.
      Spleen completely regressed in 19/25 patients. Hypersplenism resolved in all
      patients with patent shunts. CONCLUSIONS: Portosystemic shunting in children with
      EHPVO is a viable option. While long-term cure rates are comparable with
      sclerotherapy, repeated hospital visits are reduced with one time surgery. Pre
      operative and post-operative assessment can be performed with complimentary use
      of ultrasound, CTP and endoscopy.

PMID- 24741211
TI  - Meckel's diverticulum and ectopic epithelium: Evaluation of a complex
      relationship.
AB  - INTRODUCTION: Meckel's diverticulum is the most common congenital anomaly of the
      gastrointestinal tract. Currently, for any incidentally discovered Meckel's
      diverticulum, the management approach is based on weighing the statistical odds
      of future complications against the risks of a diverticulectomy. MATERIALS AND
      METHODS: The temporal relationship between age at Meckel's diverticulectomy and
      the presence of ectopic epithelium was evaluated in our series. A meta-analysis
      of all reported recent literature on this condition was subsequently performed to
      evaluate the strength of the relationship between ectopic epithelium and
      symptomatic Meckel's diverticulum. RESULTS: There was a paucity of ectopic
      epithelium in Meckel's diverticulectomy specimens in infants operated on at less
      than 1 year of age. Having two or more ectopic epithelia in a diverticulum does
      not appear to carry an additive risk for complications. The meta-analysis
      confirmed that ectopic epithelium was the most significant factor that influenced
      surgical intervention in all series of Meckel's diverticulum. CONCLUSION: The
      relationship between ectopic epithelium and the development of symptomatic
      Meckel's diverticulum is complex. Further understanding of the development of
      ectopic rests in the diverticulum will facilitate elucidating the pathophysiology
      in symptomatic cases.

PMID- 24741212
TI  - Impact of image guided fine needle aspiration cytology in diagnosis of pediatric
      hepatic mass and cytohistologic concordance.
AB  - BACKGROUND: Pediatric hepatic mass is a heterogeneous group of benign and
      malignant lesions. Percutaneous fine needle aspiration cytology (FNAC) can be
      utilized as a diagnostic modality to assess the nature of radiologically
      demonstrated hepatic lesions and thus facilitate individualized treatment. AIMS
      AND OBJECTIVE: The objective of the present study was to determine the diagnostic
      accuracy of percutaneous FNAC of pediatric liver masses, a procedure that is less
      invasive than open biopsy. MATERIALS AND METHODS: A prospective, observational
      study was carried out in the Department of Pathology in collaboration with
      Department of Pediatric surgery and Radio-diagnosis including 31 pediatric
      patients presenting over last two years (June 2011 to May 2013) with focal
      hepatic lesion on ultrasound and computed tomography (CT) scan. FNAC was carried
      out under image guidance and cytodiagnosis was reached after appropriate
      staining. By comparing with histopathology reports, diagnostic accuracy of
      cytology was evaluated. RESULT: Among 31 cases included in the study, 51.6% cases
      were cytologically benign and hemangioma was the most common benign lesion.
      Hepatoblastoma was the most accounted malignant tumour (12.9%). FNAC provided 94%
      sensitivity and 92% specificity in diagnosing benign and malignant tumours.
      Overall diagnostic accuracy was 93.10%. No significant complication was noted.
      CONCLUSION: Percutaneous FNAC under image guidance is an effective diagnostic
      tool for diagnosis of primary and metastatic tumours of liver in pediatric
      patients.

PMID- 24741213
TI  - Mitra shunt (spleen preserving, side to side lieno-renal shunt) for portal
      hypertension with hypersplenism in early infancy.
AB  - Extrahepatic portal vein obstruction (EHPVO) is the commonest cause of portal
      hypertension presenting with gastrointestinal bleeding and splenomegaly. Medical
      management of this condition may provide relief, but involves repeated hospital
      visits and endoscopic procedures. Surgery is an effective curative solution by
      lowering portal venous pressure with effective shunting of venous blood from
      splanchnic to systemic circulation. Shunt surgery for such a small baby has not
      been previously reported and splenectomy has its own problems. Similarly, banding
      or sclerotherapy in such babies is not without risk. Among the various shunt
      options, Mitra shunt (spleen preserving, side-to-side lienorenal shunt),
      developed and standardized in our own country, stands out as the most optimum
      surgical treatment for EHPVO in early infancy. We report a 4-month-old baby,
      youngest recipient of Mitra shunt reported in literature with successful outcome.

PMID- 24741214
TI  - Local peritonitis as the first manifestation of Crohn's disease in a child.
AB  - Crohn's disease (CD) can occur anywhere in the gastrointestinal tract from the
      mouth to the anus and sometimes it presents in a nonspecific manner. Herein we
      describe a case of local peritonitis as the first manifestation of CD in an 11
      year-old girl, and the subsequent method of treatment. 

PMID- 24741215
TI  - Herlyn-Weber-Wunderlich syndrome with ectopic ureter in prepubertal female.
AB  - We report a rare case of uterovaginal duplication in a prepubertal female. The
      patient also had a permeable ureter (ureter with urine passing through it)
      subtending a poorly functioning kidney with ectopic insertion in the obstructed
      hemivagina. 

PMID- 24741216
TI  - Ex-utero intrapartum treatment in the Indian scenario: Anesthetic challenges and
      positioning.
AB  - Ex-utero intrapartum treatment (EXIT) is performed for fetuses diagnosed with
      large neck masses. A case report of a fetus diagnosed with a large cystic hygroma
      and cord around the neck who was delivered by EXIT is presented. The airway
      challenges and optimal positioning is discussed. 

PMID- 24741217
TI  - Subglosso-palatal membrane a rare cause of neonatal respiratory distress: A case
      report.
AB  - Subglosso-palatal membrane is a rare cause of acute respiratory distress in
      newborn. Contrary to the earlier reported cases in which immediate splitting or
      excision of membrane has been described as measure to relief respiratory
      distress, we managed our case successfully without any emergency surgical
      procedure. 

PMID- 24741218
TI  - Pyloric stenosis in a patient with pure esophageal atresia: A difficult
      diagnosis.
AB  - Hypertrophic pyloric stenosis is brought to attention by its characteristic non
      bilious vomiting. In a patient with pure esophageal atresia and a feeding
      gastrostomy, the symptoms were modified and the diagnosis was delayed. This case
      report highlights the clinical features of this rare combination, whose diagnosis
      was easily established once the entity was considered. 

PMID- 24741219
TI  - Extraperitoneal Pelvic laparoscopic disconnection of accessory urethra from
      normal urethra in a case of urethral duplication.
AB  - We report an extraperitoneal pelvic laparoscopic approach to disconnect accessory
      urethra from normal urethra in complete urethral duplication. First stage
      consisted of chordee correction, partial excision of the accessory urethra and
      glansplasty. In the second stage the remaining accessory urethra was disconnected
      from the normal urethra through a pre-peritoneal minimal access approach to the
      retropubic space. The remaining distal mucosa was ablated using monopolar
      cautery. 

PMID- 24741220
TI  - Horseshoe kidney with multicystic dysplastic left moiety.

PMID- 24741221
TI  - Cat eye syndrome, anorectal malformation, and Hirschsprung's disease.

PMID- 24741222
TI  - Whats new in global infectious diseases? Strongyloidiasis and syndrome of
      inappropriate antidiuretic hormone secretion (SIADH).

PMID- 24741223
TI  - Studying risk factors associated with human leptospirosis.
AB  - BACKGROUND: Leptospirosis is one of the most under diagnosed and underreported
      disease in both developed and developing countries including India. It is
      established that environmental conditions and occupational habit of the
      individuals put them at risk of acquiring disease, which varies from community to
      community. Various seroprevalence studies across the world have documented
      emerging situation of this neglected tropical disease, but limited have probed to
      identify the risk factors, especially in India. OBJECTIVES: The objective of this
      study was to identify the environmental and occupational risk factors associated
      with the disease in Udupi District. MATERIALS AND METHODS: This population-based
      case-control study was carried out in Udupi, a District in Southern India from
      April 2012 until August 2012. Udupi is considered to be endemic for Leptospirosis
      and reported 116 confirmed cases in the year 2011. Seventy of 116 laboratory
      confirmed cases and 140 sex matched neighborhood healthy controls participated in
      the study. A predesigned, semi-structured and validated questionnaire was used
      for data collection through house to house visit and observations were noted
      about environmental conditions. Univariate analysis followed by multivariate
      analysis (back ward conditional logistic regression) was performed by using STATA
      version 9.2 (StataCorp, College Station, TX, USA) to identify potential risk
      factors. RESULTS: Occupational factors such as outdoor activities (matched odds
      ratio [OR] of 3.95, 95% confidence interval [CI]: 1.19-13.0), presence of cut or
      wound at body parts during work (matched OR: 4.88, CI: 1.83-13.02) and
      environmental factors such as contact with rodents through using the food
      materials ate by rat (matched OR: 4.29, CI: 1.45-12.73) and contact with soil or
      water contaminated with urine of rat (matched OR: 4.58, CI: 1.43-14.67) were the
      risk factors identified to be associated with disease. CONCLUSION: Leptospirosis
      is still considered as neglected disease in the district. Early diagnosis and
      prompt treatment of cases can save many lives. However, there is a need of
      integrated rodent control measures with great effort to increase awareness and
      education among subjects in controlling the disease.

PMID- 24741224
TI  - Hospital based infectious disease related proportional mortality study.
AB  - OBJECTIVE: To understand the temporal trends in mortality in Rural Central India.
      DESIGN: Retrospective review of physician issued death certificates from a rural
      teaching hospital. MATERIALS AND METHODS: Physician issued death certificates
      from 1979 to 2008, available with a rural teaching hospital were analyzed and
      information on age, gender, date, and cause of death was abstracted. We estimated
      cause-specific, proportional mortality ratio (PMR) stratified by age, and gender.
      We compared the difference in PMR in first fifteen years of the study period
      (period A, 1979-1993) with the later (period B, 1994-2008). RESULTS: We found
      20494 death certificates between 1979 and 2008. Proportion of infectious disease
      related mortality declined from 35% in 1979-1983-26% in 2004-2008. In the same
      periods, injury related mortality increased from 4.6% to 13.4%, and chronic
      disease mortality from 19% to 28%. The absolute difference in PMR (per 1000
      deaths) was statistically significant between period B and period A, for
      infections (a decline of 80.67 [95% CI 66.97-94.03]), chronic diseases (an
      increase of 45.85 [95% CI 33.49-58.55]), and injuries (an increase of 42.98 [95%
      CI 33.87-52.26]). CONCLUSION: Temporal trend in mortality from a single hospital
      in rural Central-India over the past three decades shows decline in infectious
      diseases, and rise in injuries and chronic diseases.

PMID- 24741225
TI  - Scrub typhus presenting as an acute abdomen.
AB  - Scrub typhus is a mite-borne infectious disease caused by Orientia tsutsugamushi,
      which presents as an acute febrile illness with headache, myalgia,
      breathlessness, and an eschar, a pathognomonic sign, in a varying proportion of
      patients. However, this illness can present unusually with fever and severe
      abdominal pain mimicking acute abdomen. A careful search for an eschar in all
      patients with an acute febrile illness would provide a valuable diagnostic clue
      and avoid unnecessary investigations and surgical exploration. 

PMID- 24741226
TI  - De-novo histoid hansen cases.
AB  - Histoid leprosy is a rare form of multibacillary leprosy with distinct clinical
      and histopathological features. It is a variant of lepromatous leprosy with a
      very high bacterial index. It appears in patients as a relapse after dapsone
      monotherapy, in the presence of dapsone resistance or rarely 'de-novo'. It is a
      matter of concern as we found three cases of de-novo Histoid that too in 3 months
      from February 2013 to April 2013; in post-global leprosy elimination era. We
      report three cases presenting with 'de-novo' Histoid Hansen's disease, with no
      history of leprosy or exposure to dapsone/multi-drug therapy, with heavy
      bacillary index. The above cases proved to be an eye opener to us in more than
      one senses. We are reporting these cases just to create awareness and avoid
      misdiagnosis which will help in prompt treatment and avoid its spread as well as
      avoid complications and deformities associated with it. 

PMID- 24741227
TI  - Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH) in Strongyloides
      stercoralis Hyperinfection.
AB  - Strongyloides stercoralis (S. stercoralis) is a soil transmitted intestinal
      roundworm that has a unique ability to multiply within the human host and
      reinfect the human carrier by a process of autoinfection. By this property, S.
      stercoralis can persist as an occult infection for many decades. In situations of
      immunosuppression or other permissive gastrointestinal conditions, there occurs a
      massive increase in parasite multiplication. The parasites penetrate through the
      intestinal mucosa and are carried in circulation and can cause multisystem
      involvement. We report a case of a 76-year-old Columbian male who presented with
      intractable vomiting and hyponatremia who was then diagnosed to have syndrome of
      inappropriate antidiuretic hormone (SIADH). The patient's symptoms improved after
      treatment with two doses of ivermectin and his serum sodium levels returned to
      normal. S. stercoralis infection should be suspected in patients from endemic
      regions who present with gastrointestinal symptoms and unexplained hyponatremia. 

PMID- 24741228
TI  - Pancreatitis in scrub typhus.
AB  - Scrub typhus is a rickettsial infection prevalent in most parts of India. Acute
      pancreatitis with pseudocyst formation is a rare complication of this condition.
      This paper reports acute renal failure, pancreatitis and pseudocyst formation in
      a 48-year-old female with scrub typhus. Ultrasonography of the abdomen revealed a
      bulky pancreas with fluid seen along the body of the pancreas in the lesser sac.
      The infection was successfully treated with doxycycline and supportive treatment.
      Pancreatitis was managed conservatively. This case report highlights the
      importance of identifying and managing uncommon complications of a common
      tropical disease for optimum outcome. 

PMID- 24741229
TI  - Acute pancreatitis due to scrub typhus.
AB  - Scrub typhus is endemic in large parts of India and can cause multi-organ failure
      and death. Acute pancreatitis as a complication is very rare and is potentially
      fatal. This case series describes seven adult patients who presented with an
      acute febrile illness and were diagnosed to have scrub typhus with acute
      pancreatitis. The mean age of the seven patients with acute pancreatitis was 49.4
      years, and mean duration of fever prior to presentation was 7.7 days. All seven
      patients had abdominal pain, and three had a pathognomonic eschar. The mean serum
      lipase level was 1,509 U/L (normal value: <190 U/L) and the mean serum amylase
      level was 434 U/L (normal value: <200 U/L). Six patients had evidence of multi
      organ dysfunction. Hematological and respiratory system dysfunction was seen in
      five patients, hepatic and renal dysfunction in four, and central nervous system
      dysfunction in three patients. Three patients who had >=4 organs involved, died
      (mortality rate: 42.8%). Our case series shows that pancreatitis in scrub typhus
      is an extremely rare complication and when present, is associated with increased
      mortality (42.8%). Physicians may be familiar with the various complications of
      scrub typhus but less so with acute pancreatitis and hence may be underdiagnosed.

PMID- 24741230
TI  - Exuberant Oral Myiasis Caused by Musca domestica (Housefly).
AB  - Tissues of oral cavity, when invaded by the parasitic larvae of houseflies, the
      condition is called as oral myiasis. It is a rare disease that is most common in
      developing countries and is associated with conditions leading to persistent
      mouth opening along with poor oral hygiene, suppurative lesions, severe halitosis
      and maxillofacial trauma. A case of exuberant oral myiasis in a 42-year-old
      female patient is described here. She reported with swelling, pain, mobility of
      teeth and foul odor. Diagnosis was based primarily on history and clinical
      features. Management included use of turpentine oil, mechanical removal of larvae
      followed by extraction of mobile teeth and curettage along with supportive
      antibiotic and analgesic therapy. Supportive nutritional supplements and timely
      institution of treatment encompassing removal of the offending larvae and carious
      teeth with proper education and motivation of the patient including oral hygiene
      instructions led to the resolution of these lesions. 

PMID- 24741231
TI  - Hemorrhagic varicella in chronic liver disease.
AB  - Hemorrhagic varicella is a serious complication of a relatively benign disorder
      and usually occurs in immunocompromised persons and those on immunosuppressive
      therapy. To the best of our knowledge, this is the first case report of
      hemorrhagic varicella associated with chronic liver disease in Indian literature.
      Our encounter with this case highlights that rare hemorrhagic varicella can also
      present in cases of chronic liver disease. Prompt diagnosis and treatment with
      acyclovir leads to complete recovery. 

PMID- 24741232
TI  - Pattern of antibiotics prescription in a referral academic hospital, northeast of
      iran.

PMID- 24741233
TI  - A case of primary cervicofacial hydatidosis.

PMID- 24741234
TI  - De-novo XDR Tuberculosis Spine in a 3-year-old Girl.

PMID- 24741235
TI  - A case of subcutaneous phaeohyphomycosis in a diabetic patient: a cryptic entity.

PMID- 24741236
TI  - Anaplasmosis.

PMID- 24741237
TI  - Perihematomal edema as predictor of outcome.

PMID- 24741238
TI  - Thrombolytic or endovascular therapy for acute ischemic stroke: Time is brain.

PMID- 24741239
TI  - The many facets of cardiac complications in epilepsy.

PMID- 24741240
TI  - Stereotactic biopsy of brain stem masses: A safe and useful procedure.

PMID- 24741241
TI  - Stereotactic biopsy of brainstem lesions: A 'golden standard' for establishing
      the diagnosis.

PMID- 24741242
TI  - Endovascular neurointervention success and complication rates in the first year
      of independent practice in a suburban hospital setup.
AB  - CONTEXT: Endovascular neurointervention (interventional neuroradiology) is a
      highly demanding science requiring deep understanding of disease, anatomy,
      clinical skills and manual dexterity, consequently with a long learning curve and
      thus posing significant challenges to a physician entering new into the
      competitive arena. AIM: To evaluate the procedural success, complications and
      outcome in the first year of independent endovascular neurointervention practice
      in a suburban hospital. MATERIALS AND METHODS: Retrospective analysis of
      prospectively maintained data of all diagnostic and therapeutic
      neurointerventional cases performed by the author between the period of January
      02, 2012 and December 31, 2012. RESULTS: A total of 61 procedures were performed.
      The performance success rate of the diagnostic procedures was 100% (38/38) and
      that of therapeutic procedures was 82.6% (19/23). The periprocedural complication
      rates were nil and 13%, respectively, for diagnostic and therapeutic procedures.
      The 3-month patient outcome for therapeutic procedures was good outcome (Modified
      Rankin Scale <2) in 87% cases (20/23), and poor outcome in 13% (2 dead and 1
      debilitated with Modified Rankin Scale of 3). CONCLUSION: For a well-trained
      endovascular neurointerventionalist, the first year of practice had high
      procedural success rate and acceptable complication with patient outcome rates
      comparable to the existing literature.

PMID- 24741243
TI  - Effect of type of secondary task on cued gait on people with idiopathic
      Parkinson's disease.
AB  - INTRODUCTION: The purpose of this study was to find out the effect of the
      secondary cognitive and motor task on cued gait in people with Idiopathic
      Parkinson's disease (PD). DESIGN AND SETTING: A repeated measure same subject
      design carried out at All India Institute of Medical Sciences, Neurology
      Department, New Delhi. MATERIALS AND METHODS: THE SUBJECTS WERE MADE TO WALK IN
      RANDOM ORDER ON A PAPER WALKWAY UNDER THREE CONDITIONS: Free walking with cues at
      preferred walking speed, coin transference while walking with cues at preferred
      walking speed and digit subtraction while walking with cues at preferred walking
      speed. OUTCOME: The stride length, cadence, walking speed and stops were
      recorded. RESULTS: There was a significant reduction in their walking speed and
      stride length, but increase in the cadence and the number of stops was seen, when
      they had to perform dual tasks along with the cued gait, but the changes were
      more pronounced when secondary cognitive task was added to the cued gait in
      people with idiopathic PD. CONCLUSION: The results of this study demonstrated
      that there is a significant difference in the effect of secondary motor task when
      compared with secondary cognitive task on cued gait parameters in people with
      Idiopathic PD.

PMID- 24741244
TI  - Commentary.

PMID- 24741245
TI  - Thrombolysis in acute ischemic stroke: Experience from a tertiary care centre in
      India.
AB  - The management of acute ischemic stroke has undergone a sea of change with the
      introduction of intravenous thrombolysis (IVT). Current guidelines state that the
      window period for IVT using rTPA is 4.5 hours. The MERCI, Multi Merci, and
      Penumbra trials in which patients with acute ischemic stroke were treated using
      endovascular treatment demonstrated better recanalisation in patients having a
      large vessel occlusion. However, recently published data from the three large
      trials IMS 3, Synthesis Expansion, and MR rescue, which compared endovascular
      treatment with intravenous therapy, failed to demonstrate superiority of
      endovascular treatment over IVT. In these trials, stent retrievers were used in
      very few patients. We present our results from a tertiary care center in India
      where patients are treated using intravenous as well as endovascular modalities.
      Among the 53 patients with acute ischemic stroke treated between 2010 and 2012,
      23 were treated with IVT and 30 with endovascular methods. Stent retriever was
      used in majority of the endovascular cases. AIMS: To compare the outcomes of
      acute ischemic stroke patients treated with IVT versus those who were managed
      using endovascular therapy. To evaluate outcomes of patients with acute ischemic
      stroke with a large vessel occlusion in whom endovascular modalities were used
      and to compare them with those of patients who were treated with IVT in presence
      of a large vessel occlusion. SETTINGS AND DESIGN: Data of patients who underwent
      thrombolysis at our centre was collected over a 3-year period, that is, from 2010
      to 2012. Endovascular treatment was done by an interventional neurologist.
      MATERIALS AND METHODS: Data of patients with acute ischemic stroke who underwent
      IVT or endovascular treatment at our centre between 2010 and 2012 was analyzed.
      Parameters included age, National Institutes of Health Stroke Scale (NIHSS) on
      admission, door to needle time, stroke subtype, modality of treatment, outcome
      based on modified Rankin Scale (mRS) Score at 90 days follow up and mortality
      rates at 90 days. STATISTICAL ANALYSIS: Tabulated results were analysed using
      INSTAT Graphpad analyser. Data were analysed using paired and unpaired t-test,
      Chi-square test, and Fishers test as applicable. P value was considered
      significant when it was <0.05. RESULTS: Upon comparison of the outcomes of
      patients with acute ischemic stroke and large vessel disease treated with
      endovascular therapy with those treated with IVT, it was found that the former
      group had better outcomes. We also found that in spite of there being a
      significant difference in the NIHSS on admission and a significant difference in
      the door to needle time, the outcomes of patients treated using intravenous or
      endovascular therapy were similar. There was no statistically significant
      difference in mortality rates between intravenous and endovascular groups.
      CONCLUSIONS: IVT is currently the standard of care in the management of acute
      ischemic stroke. Endovascular treatment during the window period is reserved for
      those patients with contraindication to IVT. In this study, we found that
      patients with documented large vessel disease with no evidence of cross flow
      through Willisian collaterals benefit from endovascular treatment. We recommend
      that all patients of acute ischemic stroke, be subjected to a baseline angiogram
      either computed tomography (CT) or magnetic resonance imaging (MRI) to document
      vessel status. This will help in identifying patients who may benefit from early
      endovascular treatment, if they fail to improve with IVT. Further, large trials
      using stent retrievers are needed, to prove that endovascular treatment is
      superior to IVT, in presence of documented large vessel disease.

PMID- 24741246
TI  - Commentary.

PMID- 24741247
TI  - Stereotactic biopsy of brainstem lesions: Techniques, efficacy, safety, and
      disease variation between adults and children: A single institutional series and
      review.
AB  - BACKGROUND: Stereotactic biopsy of brainstem lesions have been performed with
      varying indications, with most of the literature reporting on children. MATERIALS
      AND METHODS: The present study retrospectively analyzed all cases that underwent
      stereotactic biopsy for brainstem lesion in both adult and pediatric population
      between 1994 and 2009 in a single tertiary neurosurgical center. The clinical and
      radiological features, technique of the procedure, morbidity, diagnostic
      accuracy, spectrum of diagnosis, and variations in adult and pediatric population
      were analyzed. RESULTS: Eighty-two patients were included in the study. Computed
      tomography (CT) was used as guidance in 73 (38 children and 35 adults) patients
      and magnetic resonance imaging (MRI) in 9 (3 children and 6 adults). The biopsy
      was performed in a procedure room under local anesthesia in most adults, while
      children required sedation. Glioblastoma comprised 29.3% of all pathologies in
      children, compared with only 4.9% of the pathologies in adult population (P =
      0.007). Tuberculosis was the next major diagnosis (9.8%). In 12 patients, initial
      biopsy was inconclusive. Following a repeat biopsy in 5 of these patients, a
      diagnosis was possible for 75/82 (91.5%) patients by STB. The location of the
      target, the choice of entry, the radiological characteristic of the lesion,
      enhancement pattern, and age group did not significantly correlate with the
      occurrence of inconclusive biopsy. Permanent complications occurred in two
      patients (2.4%). There was no mortality in this series. CONCLUSION: Stereotactic
      biopsy has an important role in brainstem lesions, more significantly in adults,
      due to wider pathological spectrum. It can be performed safely under local
      anesthesia through a twist drill craniostomy in most of the adults.

PMID- 24741248
TI  - Role of erythrocyte sedimentation rate in ischemic stroke as an inflammatory
      marker of carotid atherosclerosis.
AB  - BACKGROUND: Inflammation mediates a key role in the pathogenesis of
      atherosclerosis which is an important cause of ischemic stroke. An elevated
      erythrocyte sedimentation rate (ESR) may, therefore, be a marker of the extent
      andor intensity of a general atherosclerotic process and thus a marker for
      advanced atherosclerosis heralding increased risk of arterial thrombosis leading
      to ischemic stroke. MATERIALS AND METHODS: ESR was calculated in ischemic stroke
      patients by Westergren's method along with carotid sonography using high
      resolution 7.5 MHz techniques to find the prevalence of increased carotid intima
      media thickness (CIMT) and presence of plaque according to Mannheim Carotid
      Intima-Media Thickness Consensus. RESULTS: Average value of ESR in all patients
      was 27.89 +/- 9.73 mm/h. A significant association was found between ESR and
      markers of carotid atherosclerosis, that is, high CIMT of more than 0.8 mm (P <
      0.0001) and presence of plaque (P-0.026) in univariate analysis. Also, a
      significant positive correlation was found between ESR and serum fibrinogen,
      another inflammatory marker. (r = 0.88, P < 0.0001). CONCLUSION: The extent of
      inflammation may reflect in part the propensity of atherosclerotic lesions to
      lead to clinical disease. Study shows the association of ESR with markers of
      atherosclerosis confirming the strength of the inflammatory response associated
      with carotid atherosclerosis and might conceivably carry important prognostic
      information regarding occurrence of such catastrophic events in future.

PMID- 24741249
TI  - Commentary.

PMID- 24741250
TI  - Commentary.

PMID- 24741251
TI  - Perihematomal edema as predictor of outcome in spontaneous intracerebral
      hemorrhage.
AB  - BACKGROUND: Spontaneous intracerebral hemorrhage (SICH) is a form of
      cerebrovascular accident with a very high rate of morbidity and mortality. The
      determinants of prognosis include the demographic, clinical, laboratory, and
      radiologic factors. It is long known that the hematoma size has a negative impact
      on the outcome in SICH. The influence of perihematomal edema (PHE) is not
      established to the extent same as that of hematoma volume. Hence, we planned this
      study to determine as to what role does PHE plays in the outcome in SICH. AIM OF
      THE STUDY: To evaluate the prognostic influence of absolute and relative edema
      (ratio of absolute edema to hematoma volume) in the patients of SICH. MATERIALS
      AND METHODS: This is a prospective case-controlled study. A total of 44 patients
      were enrolled after excluding the confounding factors. The patients were
      evaluated and their disability was assessed using modified Rankin scale (MRS).
      The imaging was done in the interval between 24 and 72 h and the hematoma volume,
      absolute edema volume, and the relative edema were calculated. The outcome was
      reassessed at 12 weeks and defined as favorable if MRS < 3. RESULTS: A total of
      69 patients were found to be having SICH on imaging; however, 25 patients were
      excluded as they had one of the criterion for exclusion. Hence, only 44 patients
      were included in the study. On univariate analysis, none of the demographic
      characteristics of the patients, vascular risk factors, presenting complaints,
      blood pressure, Glasgow coma scale, and MRS at admission, laboratory parameters
      were not significantly different in the two outcome groups. The hematoma volume
      was significantly higher in the poor outcome group (P < 0.0001) and the relative
      edema was associated with a favorable outcome at 12 weeks (P < 0.0001). On
      multivariate logistic regression, the hematoma volume and relative edema were
      found to have effect on the outcome similar to that seen on univariate analysis.
      CONCLUSION: In SICH, a larger hematoma volume is a predictor of poor outcome and
      a relative edema is associated with a better functional status.

PMID- 24741253
TI  - Commentary.

PMID- 24741252
TI  - Aneurysmatic bone cyst of the craniocervical region: Surgical technique.
AB  - Aneurysmal bone cysts (ABCs) are nonneoplastic bone lesions that may originate of
      any site of skeleton. The spine can be affect up to 30% of the cases, leading to
      pain, neurological deficits, and pathological fractures in symptomatic patients.
      The incidence of craniocervical (occipito-C1-2) occurrence is not known. We
      describe the surgical technique and clinical results of two patients with
      craniocervical ABCs that underwent primary surgical resection: An 11-year-old
      girl with a lesion in the posterior aspect of the atlas, and a 28-year-old man
      with an important hydrocephalus and a posterior expansible lesion on the left
      side of his posterior fossa. Total resection was achieved on both lesions, with
      no surgical morbidity. Even though ABCs are nonneoplastic lesions, subtotal
      resection is associated with early recurrence. The knowledge of the anatomy of
      the region in order to achieve the occlusion of arterial feeders prior to
      surgical resection itself is the key point of the surgical strategy. 

PMID- 24741254
TI  - A young patient with multisystem complications after cytomegalovirus infection.
AB  - We are describing a case of an 18-year-old male patient with cytomegalovirus
      (CMV) associated guillain-barre syndrome (GBS) who presented with an acute onset
      of generalized weakness and numbness in the extremities, dysphagia, and facial
      diplegia, followed by respiratory failure, which led to mechanical ventilation.
      He had positive immunoglobulin G and immunoglobulin M antibodies against CMV, and
      CMV polymerase chain reaction was positive with <2000 copies of deoxyribonucleic
      acid. Human immunodeficiency virus test was negative. He received a course of
      ganciclovir, intravenous immunoglobulin, and plasmapheresis. After improving from
      acute episode, patient was transferred to a rehabilitation facility for physical
      and occupational therapy. At the rehabilitation facility, he exhibited signs of
      acute abdomen with pain in the left upper quadrant secondary to peritonitis from
      dislodged gastrostomy tube and underwent exploratory laparotomy. During the
      hospital course he was found to have splenic infarct and colitis on the computed
      tomography of abdomen. This case showed an immunocompetent young patient with
      multisystem complications including guillain-barre syndrome (GBS), splenic
      infarct, hepatitis, and colitis due to CMV. 

PMID- 24741255
TI  - Guillain-Barre syndrome with posterior reversible encephalopathy syndrome.
AB  - Posterior reversible encephalopathy syndrome (PRES) is a clinicoradiologic entity
      commonly associated with eclampsia, septicemia, chemotherapeutic drugs etc.
      Concurrent occurrence of Guillain-Barre syndrome (GBS) with PRES is a rare
      entity. Dysautonomia is a proposed mechanism for such occurrence. Here we present
      a non-diabetic, non-hypertensive 63-year-old male patient, who came with acute
      onset flaccid quadriparesis, developing generalized seizures, altered sensorium
      and raised blood pressure on fifth day of illness. Magnetic resonance imaging
      (MRI) of brain showed altered signal intensities involving the parieto-occipital
      areas suggestive of posterior reversible encephalopathy. Cerebrospinal fluid
      analysis showed albuminocytological dissociation, nerve conduction studies
      revealed demyelinating type of polyneuropathy. The patient was treated with
      antihypertensives and antiepileptics. After resolution of the encephalopathy,
      intravenous immunoglobulin (IVIg) was given. The patient recovered gradually over
      few months. Our case concludes GBS as independent risk factor, for PRES may be
      secondary to dysautonomia and physicians should be aware of such rare coexistence
      so that early treatment can be done to reduce the mortality and morbidity. 

PMID- 24741256
TI  - Commentary.

PMID- 24741257
TI  - Neonatal meningitis complicating with pneumocephalus.
AB  - Pneumocephalus is a rare condition characterized by the presence of gas within
      the cranial cavity. This gas may arise either from a trauma, a tumor, a surgical,
      or a diagnostic procedure or occasionally from an infection. Pneumocephalus as a
      complication of bacterial meningitis, in absence of trauma or a procedure, is
      extremely rare, particularly in a newborn. A case of pneumocephalus occurring in
      a baby, suffering from neonatal meningitis, acquired probably through unsafe
      cutting and tying of the cord, is reported here. Cutting, tying, and care of the
      umbilical cord is of utmost importance to prevent neonatal infection as the same
      is a potential cause of serious anaerobic infections, besides tetanus. 

PMID- 24741258
TI  - Commentary.

PMID- 24741259
TI  - Posterior reversible encephalopathy syndrome with PLEDs-plus due to mesalamine.
AB  - A 32-year-old lady developed status epilepticus and acute visual loss while on
      mesalamine for Crohn's disease. Her clinical course and magnetic resonance
      imaging (MRI) were suggestive of posterior reversible encephalopathy syndrome
      (PRES). She had periodic lateralized epileptiform discharges plus (PLEDs-plus) on
      electroencephalogram (EEG), which responded to sodium valproate. Her vision
      improved from counting fingers at one-meter distance to 6/12. Though different
      cytotoxic drugs have been implicated as causative agents, this is the first case
      report of mesalamine-induced PRES. This case highlights the need for aggressive
      treatment of PLEDs-plus with EEG monitoring using a broad-spectrum antiepileptic
      drug like valproate, which has contributed to the rapid reversibility of vision
      in PRES subjects, and the need for a thorough drug history for etiological clues.

PMID- 24741260
TI  - Neurocysticercosis presenting as pseudobulbar palsy.
AB  - Neurocysticercosis (NCC) is the most common helminthic infestation of the central
      nervous system (CNS) and a leading cause of acquired epilepsy worldwide. The
      common manifestations of NCC are seizures and headache. The NCC as a cause of
      pseudobulbar palsy is very unusual and not reported yet in the literature. A
      pseudobulbar palsy can occur in any disorder that causes bilateral corticobulbar
      disease. The common etiologies of pseudobulbar palsy are vascular, demyelinative,
      or motor neuron disease. We report a 38-year-old female patient who presented
      with partial seizures and pseudobulbar palsy. The MRI brain showed multiple small
      cysts with scolex in both the cerebral hemispheres and a giant intraparenchymal
      cyst. Our patient responded well to standard treatment of neurocysticercosis and
      antiepileptics. 

PMID- 24741261
TI  - Combined central and peripheral demyelination.
AB  - Acquired central and peripheral demyelination in the same patient is a very rare
      feature. We report a 52-year-male patient with the chronic autoimmune hepatitis
      (CAH) presenting with pure motor areflexic quadriparesis from 4 months and recent
      onset of drowsiness of 4 days duration. Studies of imaging and electrophysiology
      suggested central pontine myelinolysis and chronic inflammatory demyelinating
      polyradiculoneuropathy. Patient was effectively treated with high dose steroids.
      To the best of our knowledge, this is the first case of central and peripheral
      demyelination in a patient with CAH. 

PMID- 24741262
TI  - Chiari Type I malformation yielded to the diagnosis of Crouzon syndrome.
AB  - Chiari malformation Type I (CM-I) related to syndromic craniosynostosis in
      pediatric patients has been well-studied. The surgical management consists of
      cranial vault remodeling with or without posterior fossa decompression. There
      were also cases, in whom CM-I was diagnosed prior to the craniosynostosis in
      early childhood. We present a 16-year-old boy who admitted with symptoms related
      to CM-I. With careful examination and further genetic investigations, a diagnosis
      of Crouzon syndrome was made, of which the patient and his family was unaware
      before. The patient underwent surgery for posterior fossa decompression and
      followed-up for Crouzon's syndrome. To our knowledge, this is the only case
      report indicating a late adolescent diagnosis of Crouzon syndrome through
      clinical symptoms of an associated CM-I. 

PMID- 24741263
TI  - Central and peripheral demyelination.
AB  - Several conditions cause damage to the inherently normal myelin of central
      nervous system, perepheral nervous system or both central and perepheral nervous
      system and hence termed as central demyelinating diseases, perepheral
      demyelinating diseases and combined central and perepheral demyelinating diseases
      respectively. Here we analysed and foccused on the etiology, prevalance,
      incidence and age of these demyelinating disorders. Clinical attention and
      various diagnostic tests are needed to adequately assess all these possibilities.

PMID- 24741264
TI  - Intracranial plasmacytoma mimicking meningioma.

PMID- 24741265
TI  - Emergent management with favorable outcome of an unusual presentation of a
      primary CNS lymphoma in an immunocompetent patient.

PMID- 24741266
TI  - Emergent management with favorable outcome of an unusual presentation of a
      primary central nervous system lymphoma in an immunocompetent patient.

PMID- 24741267
TI  - Pericallosal lipoma associated with subcutaneous lipoma in an adult.

PMID- 24741268
TI  - Careful consideration for use of triptans for the control of headache in
      bacterial meningitis.

PMID- 24741269
TI  - Use of triptans for the control of headache in bacterial meningitis.

PMID- 24741270
TI  - Application of PET-MRI in pseudo progression versus true progression in High
      Grade Gliomas: A new avenue!

PMID- 24741271
TI  - Molecular characterization of neuroprotective activities of plant based products
      could revive their utilization and lead discovery of new drug candidates for
      brain diseases.

PMID- 24741272
TI  - Anti-helminthic drugs in recurrent apthous stomatitis: A short review.
AB  - Recurrent aphthous stomatitis (RAS) is a common mucosal condition producing
      painful ulcerations in the oral cavity and considerable clinical morbidity. The
      etiology remains obscure, though local trauma, psychologic stress, hematinic
      deficiencies and immune dysregulation have been implicated. Though the primary
      goals of therapy are symptomatic relief of pain, the clinicians are aiming toward
      reducing the frequency, duration, number of ulcerations and increasing ulcer free
      periods with systemic drug therapy if topical medications appear ineffective.
      Levamisole, an antihelminthic drug has been tried with promising results in
      patients with severe RAS providing long-term benefits. 

PMID- 24741273
TI  - A review exploring biological activities of hydrazones.
AB  - The development of novel compounds, hydrazones has shown that they possess a wide
      variety of biological activities viz. antimicrobial, anticonvulsant,
      antidepressant, anti-inflammatory, analgesic, antiplatelet, antimalarial,
      anticancer, antifungal, antitubercular, antiviral, cardio protective etc.,
      Hydrazones/azomethines/imines possess-NHN = CH- and constitute an important class
      of compounds for new drug development. A number of researchers have synthesized
      and evaluated the biological activities of hydrazones. This review aims at
      highlighting the diverse biological activities of hydrazones. 

PMID- 24741274
TI  - Pros and cons of phospholipid asymmetry in erythrocytes.
AB  - Phospholipids of erythrocyte are found as bilayer with choline containing
      phospholipid like phosphatidyl choline and sphingomylein in the outer layer and
      amine containing phospholipid like phosphatidyl ethanolamine and phosphatidyl
      serine in the inner layer. This arrangement is known as phospholipid asymmetry.
      Lipid asymmetry is maintained throughout the entire life span of red blood cell
      and is disturbed when cells enter into the stage of apoptosis. We here discuss
      some of the conditions in which phospholipid asymmetry of erythrocyte is
      maintained and disturbed and the various detection methods to check the
      distortion phospholipid asymmetry of it. 

PMID- 24741275
TI  - Comparative study on anti-oxidant and anti-inflammatory activities of Caesalpinia
      crista and Centella asiatica leaf extracts.
AB  - BACKGROUND: Amyloidosis, oxidative stress and inflammation have been strongly
      implicated in neurodegenerative disorders like Alzheimer's disease.
      Traditionally, Caesalpinia crista and Centella asiatica leaf extracts are used to
      treat brain related diseases in India. C. crista is used as a mental relaxant
      drink as well as to treat inflammatory diseases, whereas C. asiatica is reported
      to be used to enhance memory and to treat dementia. OBJECTIVE: The present study
      is aimed to understand the anti-oxidant and anti-inflammatory potential of C.
      asiatica and C. crista leaf extracts. MATERIALS AND METHODS: Phenolic acid
      composition of the aqueous extracts of C. crista and C. asiatica were separated
      on a reverse phase C18 column (4.6 x 250 mm) using HPLC system. Antioxidant
      properties of the leaf extracts were determined by 1,1-diphenyl-2-picrylhydrazyl
      (DPPH) radical scavenging assay and the reducing potential assay. The anti
      inflammatory activities of aqueous extracts of C. crista and C. asiatica were
      studied using 5-lipoxygenase assay. Polymorphonuclear leukocytes (PMNLs) were
      isolated from blood by Ficoll-Histopaque density gradient followed by hypotonic
      lysis of erythrocytes. RESULTS: Gallic, protocatechuic, gentisic, chlorogenic,
      caffeic, p-coumaric and ferulic acids were the phenolic acids identified in C.
      crista and C. asiatica leaf aqueous extracts. However, gallic acid and ferulic
      acid contents were much higher in C. crista compared to C. asiatica. Leaf
      extracts of C. asiatica and C. crista exhibited antioxidant properties and
      inhibited 5-lipoxygenase (anti-inflammatory) in a dose dependent manner. However,
      leaf extracts of C. crista had better antioxidant and anti-inflammatory activity
      compared to that of C. asiatica. The better activity of C. crista is attributed
      to high gallic acid and ferulic acid compared to C. asiatica. CONCLUSIONS: Thus,
      the leaf extract of C. crista can be a potential therapeutic role for Alzheimer's
      disease.

PMID- 24741276
TI  - Studies on gum of Moringa oleifera for its emulsifying properties.
AB  - BACKGROUND: Emulsion has been a form of presenting water insoluble substances for
      a long period of time. Now a day, it has been a way of presenting various
      intravenous additives and diagnostic agents in X-ray examinations. Various
      substances can be used as emulsifying agent, which can be operationally defined
      as a stabilizer of the droplets formed of the internal phase. MATERIALS AND
      METHODS: Gum from Moringa oleifera was evaluated for its emulsifying properties.
      Castor oil emulsions 30 percent (o/w), containing 2 to 4% Moringa oleifera gum
      was prepared. Emulsions containing equivalent concentration of acacia were also
      prepared for comparison. All the emulsions prepared were stored at room
      temperature and studied for stability at various time intervals for 8 weeks. The
      prepared emulsions were evaluated for creaming rate, globule size and rate of
      coalescence. 23 factorial design was chosen to investigate the effects of
      centrifugation, pH, temperature changes and electrolytes on the creaming rate and
      globule size. RESULTS: The results of the investigations show that the gum of
      Moringa oleifera possesses better emulsifying properties as compared to gum
      acacia. CONCLUSION: Gum of Moringa oleifera could be used in pharmaceutical and
      non-pharmaceutical preparation.

PMID- 24741277
TI  - The effects of Valeriana officinalis L. hydro-alcoholic extract on depression
      like behavior in ovalbumin sensitized rats.
AB  - BACKGROUND: Neuroimmune factors have been considered as contributors to the
      pathogenesis of depression. Beside other therapeutic effects, Valeriana
      officinalis L., have been suggested to have anti-inflammatory effects. In the
      present study, the effects of V. officinalis L. hydro alcoholic extract was
      investigated on depression like behavior in ovalbumin sensitized rats. MATERIALS
      AND METHODS: A total of 50 Wistar rats were divided into five groups: Group 1
      (control group) received saline instead of Valeriana officinalis L. extract. The
      animals in group 2 (sensitized) were treated by saline instead of the extract and
      were sensitized using the ovalbumin. Groups 3-5 (Sent - Ext 50), (Sent - Ext 100)
      and (Sent - Ext 200) were treated by 50, 100 and 200 mg/kg of V. officinalis L.
      hydro-alcoholic extract respectively, during the sensitization protocol. Forced
      swimming test was performed for all groups and immobility time was recorded.
      Finally, the animals were placed in the open-field apparatus and the crossing
      number on peripheral and central areas was observed. RESULTS: The immobility time
      in the sensitized group was higher than that in the control group (P < 0.01). The
      animals in Sent-Ext 100 and Sent-Ext 200 groups had lower immobility times in
      comparison with sensitized group (P < 0.05 and P < 0.01). In the open field test,
      the crossed number in peripheral by the sensitized group was higher than that of
      the control one (P < 0.01) while, the animals of Sent-Ext 50, Sent-Ext 100 and
      Sent-Ext 200 groups had lower crossing number in peripheral compared with the
      sensitized group (P < 0.05 and P < 0.01 respectively). Furthermore, in the
      sensitized group, the central crossing number was lower than that of the control
      group (P < 0.001). In the animals treated by 200 mg/kg of the extract, the
      central crossing number was higher than that of the sensitized group (P < 0. 05).
      CONCLUSIONS: The results of the present study showed that the hydro-alcoholic
      extract of V. officinalis prevents depression like behavior in ovalbumin
      sensitized rats. These results support the traditional belief on the about
      beneficial effects of V. officinalis in the nervous system. Moreover, further
      investigations are required in order to better understand this protective effect.

PMID- 24741278
TI  - Barriers to and determinants of medication adherence among hypertensive patients
      attended National Health Service Hospital, Sunderland.
AB  - BACKGROUND: Hypertension is a silent killer, a time bomb in both the developed
      and developing nations of the world. It is one of the most significant risk
      factors for cardiovascular morbidity and mortality resulting from target-organ
      damage to blood vessels in the heart, brain, kidney and eyes. Adherence to long
      term therapy for chronic illnesses like hypertension is an important tool to
      enhance the effectiveness of pharmacotherapy. OBJECTIVE: The two objectives of
      this study were to evaluate the extent and reasons of non-adherence in patients
      attended National Health Service (NHS) Hospital, Sunderland. MATERIALS AND
      METHODS: The study was conducted for 4 months in the out-patient department of
      NHS Hospital. A total of 200 patients were selected randomly for this study.
      Morisky's Medication Adherence Scale was used to assess the adherence rate and
      the reason of non-adherence. Data were entered and analyzed using Microsoft Excel
      2010. RESULTS: The overall adherence rate was found to be 79% (n = 158).
      Adherence rate in females were low was compared with their male counterparts
      (74.7% vs. 85.7%). The higher rate of adherence was found in age group of 30-40
      years (82%, n = 64). The major intentional and non-intentional reason of non
      adherence was side-effects and forgetfulness respectively. CONCLUSION: Overall,
      more than three-fourth of the hypertensive participants were found to be adherent
      to their treatment. On the basis of factors associated with non-adherence, it is
      analyzed that suitable therapy must be designed for patients individually to
      increase medication adherence and its effectiveness.

PMID- 24741279
TI  - Valeriana officinalis L. for conscious sedation of patients submitted to impacted
      lower third molar surgery: A randomized, double-blind, placebo-controlled split
      mouth study.
AB  - INTRODUCTION: Anxiety is one of the components of patient stress in the dental
      office and is recognized as one of the main factors that negatively affect
      treatment. The control of anxiety can be performed through conscious sedation,
      for which benzodiazepine is the drug of choice in dental practice, however
      present side-effects. OBJECTIVE: The objective of the following study is to
      evaluate the efficacy of Valeriana officinalis L. (Valerian) for control of
      anxiety during the third molar surgery. MATERIALS AND METHODS: A single oral dose
      of either Valerian (100 mg) or placebo was randomly administered 1 h before each
      surgical procedure to 20 volunteers between 17 and 31 years of age. Anxiety level
      was assessed by physiological parameters (blood pressure and heart rate [HR]) and
      the observation of signs. Descriptive analysis, Chi-square test, Friedman test,
      Wilcoxon test and effect size test were performed (P < 0.05). RESULTS: According
      to the researcher's (80%) and surgeon's (75%) evaluations, the patients treated
      with Valerian were calmer and more relaxed during surgery. Valerian had a greater
      effect on the maintenance of systolic blood pressure and HR after surgery.
      CONCLUSION: Valerian was more effective at controlling anxiety than a placebo
      when used for the conscious sedation of adult patients submitted to impacted
      lower third molar surgery.

PMID- 24741280
TI  - A polymerase chain reaction and enzyme linked immunosorbent assay based approach
      for diagnosis and differentiation between vaccinated and infected cattle with
      Mycobacterium bovis.
AB  - BACKGROUND: In most African and Arabic countries tuberculosis (TB) causes great
      economic losses in bovine species and constitutes serious zoonotic problem. As
      the traditional diagnostic method delay the research because of low sensitivity
      and specificity, a rapid method of diagnosis is of outmost importance. AIM: The
      study was designed to evaluate the two rapid diagnostic methods of TB in cattle,
      further to differentiate between infected and bacillus Calmette-Guerin (BCG)
      vaccinated animals. MATERIALS AND METHODS: Intradermal tuberculin test was
      applied to 300 cattle. Of these cattle, 15 cattle were vaccinated from cattle
      negative to tuberculin test with BCG. Blood samples were taken for lymphocyte
      separation to apply polymerase chain reaction (PCR) upon and for serum
      preparation for the enzyme-linked immunosorbent assay (ELISA) application, this
      blood collected from 65 cattle classified into three groups, viz. positive
      tuberculin test (35 animals), negative tuberculin test (15 animals), and
      vaccinated cow with BCG (15 animals). From blood samples lymphocytes were
      separated and the isolated lymphocytes were subjected to PCR and serum for ELISA
      application. Blood samples, specimens from lymph nodes and specific tissues were
      taken for PCR and for cultivation and isolation of Mycobacterium bovis. RESULTS
      AND CONCLUSIONS: The results of this study revealed that PCR can be used as rapid
      efficient and accurate diagnostic test in detection of ruminant TB. Moreover,
      cattle's ELISA reading showed higher sensitivity in positive tuberculin animals.
      However, the differentiations between vaccinated and infected animals not clear
      by using a single antigen only.

PMID- 24741281
TI  - Desquamative gingivitis - A clinical sign in mucous membrane pemphigoid: Report
      of a case and review of literature.
AB  - Gingival desquamation is a clinical sign in which the gingiva appears reddish,
      glazed and friable with destruction of the epithelium. Gingival desquamation may
      be the result of various disease processes in gingiva. Mucous membrane pemphigoid
      (MMP), oral lichen planus and pemphigus vulgaris accounts for the major causes of
      gingival desquamation. MMP is a rare, chronic autoimmune blistering disorder
      characterized by subepithelial bullae. The condition frequently involves mucous
      membranes, with rare skin involvement. Oral cavity is mostly affected and
      desquamative gingivitis is the most common manifestation. Hereby, we present an
      interesting case of MMP manifesting as desquamative gingivitis, along with a
      brief review of the literature. 

PMID- 24741282
TI  - Platelet rich fibrin and alloplast in the treatment of intrabony defect.
AB  - Periodontal regeneration is defined as the reproduction or reconstitution of a
      lost or injured part to restore the architecture and function of the
      periodontium. The ultimate goal of periodontal therapy is to regenerate the lost
      periodontal tissues caused by periodontitis. The most positive outcome of
      periodontal regenerative procedures in intra bony defect has been achieved with
      bone grafts. For complete regeneration, delivery of growth factors in a local
      environment holds a great deal in adjunct to bone grafts. Platelet rich fibrin
      (PRF) is considered as second generation platelet concentrate, consisting of
      viable platelets, releasing various growth factors. Hence, this case report aims
      to investigate the clinical and radiological (bone fill) effectiveness of
      autologous PRF along with the use of alloplastic bone mineral in the treatment of
      intra bony defects. 

PMID- 24741283
TI  - Canagliflozin - Beginning of the journey.

PMID- 24741284
TI  - Platelet rich concentrates: A quick healer.

PMID- 24741285
TI  - Negative animal studies published in Indian Medical Journal: Are they
      methodologically strong enough to conclude what they are concluding?

PMID- 24741286
TI  - SUPPORTING CHILDREN IN U.S. LEGAL PROCEEDINGS: Descriptive and Attitudinal Data
      From a National Survey of Victim/Witness Assistants.
AB  - We conducted a national survey of 786 victim/witness assistants (VWAs) to provide
      descriptive and attitudinal information about support person use in U.S. legal
      proceedings involving children. VWAs (N = 414) from 46 states returned completed
      surveys (response rate = 53%). Prosecutor-based VWAs or parents/guardians most
      frequently served as support persons. One support person was almost always or
      often used with child victims and/or witnesses of all ages. Support persons were
      extremely common in cases involving child sexual abuse, physical abuse, neglect,
      and adult domestic violence. Overall, support persons provided more informational
      than emotional support. The most common informational support was to provide
      referrals to community resources, conduct courtroom visit/orientation, and
      disseminate relevant procedural information. The most common emotional support
      was to accompany the child to trial. Support persons rarely or never questioned
      children directly during investigative interviews or in court. Respondents
      believed support persons decrease children's stress and increase accuracy and
      credibility; however, this effect varied as a function of who provided support,
      child age, case type, and type of emotional or informational support. Respondents
      believed that support person presence at trial probably does not prejudice jurors
      against defendants. These survey data provide a benchmark for legal professionals
      and a foundation for future social scientific research examining the effects of
      support person use on children.

PMID- 24741287
TI  - Comparison of efficacy between low-fluence and half-dose verteporfin photodynamic
      therapy for chronic central serous chorioretinopathy.
AB  - PURPOSE: To compare the efficacy of low-fluence photodynamic therapy (PDT) and
      PDT with half-dose verteporfin in chronic central serous chorioretinopathy (CSC).
      PATIENTS AND METHODS: The medical records of 64 eyes from 60 patients with
      chronic CSC were retrospectively reviewed; 36 eyes received low-fluence PDT (25
      J/cm(2)) and 28 eyes received half-dose verteporfin PDT (3 mg/m(2)). The primary
      outcome measure was the proportion of eyes with complete resolution of subretinal
      fluid. Secondary outcome measures were the changes in best corrected visual
      acuity (BCVA) and central foveal thickness, and the proportion of eyes that
      showed an increase of >=5 letters in BCVA at the last visit. RESULTS: The mean
      follow-up period was 12.5+/-4.3 months and 13.1+/-4 months in the low-fluence
      group and half-dose group, respectively (P=0.568). Thirty-three eyes (91.6%) in
      the low-fluence group and 26 eyes (92.8%) in the half-dose verteporfin group
      showed complete resolution of subretinal fluid (P=0.703). BCVA increased by a
      mean of 7.4 letters and 4.8 letters in the low-fluence group and half-dose group,
      respectively (P=0.336). Seventeen eyes (52.8%) in the low-fluence group and 14
      eyes (50%) in the half-dose group experienced a gain of >=5 letters in BCVA
      (P=0.825). In the low-fluence and half-dose verteporfin group, the mean baseline
      central foveal thickness was 351+/-90 MUm and 341+/-96 MUm, and significantly
      decreased to 188+/-61 MUm and 181+/-47 MUm, respectively (P<0.01). CONCLUSION:
      Both treatments resulted in complete subretinal fluid resolution in most of the
      eyes, with significantly better visual acuity outcomes compared to baseline at
      the last visit.

PMID- 24741288
TI  - Role of the Vision Van, a mobile ophthalmic outpatient clinic, in the Great East
      Japan Earthquake.
AB  - PURPOSE: The Great East Japan Earthquake of March 11, 2011 triggered powerful
      tsunami waves off the northeastern Pacific coast of Japan that destroyed almost
      all of the built-up areas along the coast. The study reported here examined the
      role played by the Vision Van, a mobile outpatient ophthalmological clinic, in
      providing eye care to disaster evacuees. METHODS: This was a retrospective case
      series study of 2,070 victims (male: 732, female: 1,338) who visited the Vision
      Van. The subjects' medical records were examined retrospectively and analyzed in
      terms of age, sex, and date of visit to the Vision Van. Information regarding
      each patient's chief complaint, diagnosis, medication(s) prescribed, and
      eyeglasses and contact lenses provided, was also examined. RESULTS: The Vision
      Van was used to conduct medical examinations on 39 days between April 23 and June
      29, 2011. The average number of subjects visiting the Vision Van each day was
      53+/-31 (range: 7-135), with examinations carried out in Miyagi Prefecture and
      Iwate Prefecture. The most frequent complaint was a need for eye drops (871/2,070
      [42.1%]). The second and third most frequent complaints, respectively, were the
      need for contact lenses (294/2,070 [14.2%]) and eyeglasses (280/2,070 [13.5%]).
      The most frequent ocular disease diagnosis was cataract (497/2,070 [24.0%]). Eye
      drops were prescribed to 74.1% of the subjects. CONCLUSION: Mobile clinics such
      as the Vision Van provide valuable care, in this case, particularly to
      individuals who lost or left behind eyeglasses or contact lenses while escaping a
      natural disaster, and to subjects with chronic eye disease.

PMID- 24741289
TI  - Novel myopic refractive correction with transepithelial very high-fluence
      collagen cross-linking applied in a customized pattern: early clinical results of
      a feasibility study.
AB  - BACKGROUND: The purpose of this study is to report the safety and efficacy of a
      new application of collagen cross-linking using a novel device to achieve
      predictable refractive myopic changes in virgin corneas. METHODS: Four cases were
      treated with a novel device employing very high-fluence collagen cross-linking
      applied in a myopic pattern. Prior to treatment, riboflavin solution was applied
      to the intact epithelium. The collagen cross-linking device was then engaged for
      a total of 12 J/cm(2), to be applied transepithelially in a predetermined
      pattern. Cornea clarity, corneal keratometry, and corneal topography were
      evaluated by both Placido disc and Scheimpflug imaging, along with cornea
      anterior segment optical coherence tomography and endothelial cell counts.
      RESULTS: An average of 2.3 diopters was achieved in the first week in all four
      cases treated with the very high-fluence myopic collagen cross-linking
      intervention. There was a slight regression to 1.44 diopters at 1 month, which
      remained stable at 6-month follow-up. The mean keratometry change was from 44.90
      diopters to 43.46 diopters. There was no significant change in endothelial cell
      counts or corneal clarity. There was some mild change in epithelial thickness
      distribution, with the treated area showing a slight but homogeneous reduction in
      mean thickness from 52 MUm to 44 MUm. CONCLUSION: This report describes the novel
      application of very high-fluence collagen cross-linking with a predictable well
      defined myopic refractive (flattening) corneal effect. This technique has the
      advantages of essentially no postoperative morbidity, immediate visual
      rehabilitation, and the potential for tapering until the desired result is
      achieved.

PMID- 24741290
TI  - Miniaturized high-resolution wide-field contact lens for panretinal
      photocoagulation.
AB  - BACKGROUND AND OBJECTIVE: We describe a miniaturized lightweight high-refractive
      index panretinal contact lens for diagnostic and therapeutic visualization of the
      peripheral retina. INSTRUMENT DESIGN: The miniaturized high-resolution wide-field
      contact lens includes three optical elements in a light (15 g) and miniaturized
      (16 mm footplate, 24 mm external aperture, and 21 mm vertical height) casing
      contributing to a total dioptric power of +171 diopters. This lens provides up to
      165 degrees  visualization of the retina for diagnostic and therapeutic
      applications while allowing easier placement due to its miniaturization.
      CONCLUSION: This new lens (50% lighter and 89% smaller) improves upon earlier
      contact lenses for visualization of the peripheral retina.

PMID- 24741291
TI  - Tolosa-Hunt syndrome masquerading as a carotid artery dissection.
AB  - PURPOSE: To demonstrate the difficulties of diagnosing a patient with Tolosa-Hunt
      syndrome (THS) due to its complicated presentation and extensive diagnostic
      testing, and how to manage the treatment of a patient in an emergent setting.
      PATIENTS AND METHODS: A female patient with THS affecting the left eye was
      examined using two magnetic resonance imaging (MRI) scans. The patient was
      treated with high-dose methylprednisolone (Solu-Medrol((r))) and prednisone. A
      follow-up MRI and magnetic resonance angiogram (MRA) was also performed 4 months
      later. RESULTS: The second MRI scan disclosed a 5*9*10 mm lesion in the left
      superior orbital fissure/cavernous sinus. After administration of
      methylprednisolone and prednisone, the patient's pain completely resolved, and
      the left eye regained full duction and eyelid mobility. The MRI and MRA obtained
      after the treatment showed no abnormalities. CONCLUSION: The rarity of THS makes
      it difficult to diagnose, especially when there is a question of accuracy and
      reproducibility of the testing performed. An ophthalmologic consultation in such
      cases is crucial.

PMID- 24741292
TI  - Advancing personalized care in hemophilia A: ten years' experience with an
      advanced category antihemophilic factor prepared using a plasma/albumin-free
      method.
AB  - Detailed analysis of data from studies of recombinant antihemophilic factor
      produced using a plasma/albumin-free method (rAHF-PFM) in previously treated
      patients showed a substantial level of interpatient variation in pharmacokinetics
      (PKs), factor VIII dosing, and annualized bleed rate (ABR), suggesting that
      individual patient characteristics contributed to outcome. For example, plasma
      half-life (t1/2), recovery, and clearance appeared to differ between patients
      aged <6 years and 10-65 years. Prophylaxis resulted in lower ABRs than episodic
      treatment in both age groups; better adherence to the prophylactic regimen
      resulted in a lower ABR in patients aged 10-65 years. The weekly frequency of
      dosing and adherence to dosing were both significantly and inversely related to
      the rate of bleeding (young children, P<0.0001 for both all bleeds and joint
      bleeds; older patients, P<0.0001 for all bleeds and P<0.05 for joint bleeds), as
      was adherence to dosing frequency (P<0.0001 for all comparisons). A post
      marketing randomized study of prophylaxis demonstrated that a PK-guided dosing
      regimen, based on an individual patient's rAHF-PFM PK (infusion interval,
      estimated t1/2, and recovery), was as effective as standard prophylaxis and that
      both prophylactic regimens were superior to episodic treatment with respect to
      ABR and quality of life measures. Thus, compared with standard prophylaxis, the
      PK-guided regimen achieved comparable efficacy with fewer weekly infusions. A two
      compartment population PK model describes the PK data across the entire age range
      and forms the basis for future PK-guided therapy with rAHF-PFM. The model
      confirmed a shorter t1/2 and faster clearance of rAHF-PFM in children <6 years of
      age versus patients >=10 years and predicted similar PK parameters with either a
      full or reduced blood sampling schedule, offering the potential for the use of PK
      guided, individualized treatment in the routine clinical care setting. 

PMID- 24741293
TI  - Monoclonal antibodies in rheumatoid arthritis: comparative effectiveness of
      tocilizumab with tumor necrosis factor inhibitors.
AB  - Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by
      persistent joint inflammation, systemic inflammation, and immunological
      abnormalities. Because cytokines such as tumor necrosis factor (TNF)-alpha and
      interleukin (IL)-6 play a major role in the development of RA, their targeting
      could constitute a reasonable novel therapeutic strategy for treating RA. Indeed,
      worldwide clinical trials of TNF inhibiting biologic disease modifying
      antirheumatic drugs (bDMARDs) including infliximab, adalimumab, golimumab,
      certolizumab pegol, and etanercept as well as the humanized anti-human IL-6
      receptor antibody, tocilizumab, have demonstrated outstanding clinical efficacy
      and tolerable safety profiles, resulting in worldwide approval for using these
      bDMARDs to treat moderate to severe active RA in patients with an inadequate
      response to synthetic disease modifying antirheumatic drugs (sDMARDs). Although
      bDMARDs have elicited to a paradigm shift in the treatment of RA due to the
      prominent efficacy that had not been previously achieved by sDMARDs, a
      substantial percentage of patients failed primary or secondary responses to
      bDMARD therapy. Because RA is a heterogeneous disease in which TNF-alpha and IL-6
      play overlapping but distinct pathological roles, further studies are required to
      determine the best use of TNF inhibitors and tocilizumab in individual RA
      patients. 

PMID- 24741294
TI  - Discovery and evaluation of asymmetrical monocarbonyl analogs of curcumin as anti
      inflammatory agents.
AB  - Sepsis is a systemic inflammatory response syndrome and is mainly caused by
      lipopolysaccharides (LPS) - a component of the cell walls of gram-negative
      bacteria, via toll-like receptor 4-mitogen-activated protein kinases/nuclear
      factor-kappa B-dependent proinflammatory signaling pathway. Here, we synthesized
      26 asymmetric monocarbonyl analogs of curcumin and evaluated their anti
      inflammatory activity by inhibiting the LPS-induced secretion of tumor necrosis
      factor-alpha and interleukin-6 in mouse RAW264.7 macrophages. Five active
      compounds (3a, 3c, 3d, 3j, and 3l) exhibited dose-dependent inhibition against
      the release of tumor necrosis factor-alpha and interleukin-6, and they also
      showed much higher chemical stability than curcumin in vitro. The anti
      inflammatory activity of analogs 3a and 3c may be associated with their
      inhibition of the phosphorylation of extracellular signal-regulated kinase and
      the activation of nuclear factor-kappa B. In addition, 3c exhibited significant
      protection against LPS-induced septic death in vivo. These results indicate that
      asymmetrical monocarbonyl curcumin analogs may be utilized as candidates for the
      treatment of acute inflammatory diseases.

PMID- 24741295
TI  - Adherence to intermittent preventive treatment for malaria with sulphadoxine
      pyrimethamine and outcome of pregnancy among parturients in South East Nigeria.
AB  - BACKGROUND: Intermittent preventive treatment of malaria for pregnant women
      (IPTp) is a very important strategy for the control of malaria in pregnancy in
      malaria-endemic tropical countries, where mosquito bites easily occur during
      evening outdoor activities. Issues related to provision, cost, and acceptability
      may affect the use of IPTp in some developing countries. The aim of the study was
      to assess the uptake and adherence to sulphadoxine-pyrimethamine-based
      intermittent preventive treatment of malaria during pregnancy and the
      relationship of IPTp use to pregnancy outcomes in two major obstetric centers in
      South East Nigeria. METHODS: This was a prospective descriptive study involving
      women who received antenatal and delivery services. All recruited women were
      followed-up from booking until delivery, and statistical analysis was done with
      Epi Info version 7. RESULTS: A total of 516 parturients were studied. The mean
      gestational age at booking was 21.8+/-6.9 weeks while the mean number of
      antenatal visits throughout the pregnancy was 5.5+/-3.1. The rate of uptake of at
      least one dose of prescribed IPTp was 72.1% (367/516). Of the 367 who took
      prescribed IPTp, adherence to second doses of IPTp was 59.7% (219/367), and only
      4.9% (18/367) took a third dose. Clinical malaria occurred in 85% (127/149) of
      women who did not receive IPTp at all compared to 20.5% of those who received at
      least one dose of IPTp. All those who had clinical malaria despite IPTp had only
      one dose of IPTp despite booking in the second trimester. Malaria in pregnancy
      occurred significantly more in women who failed to adhere to subsequent doses of
      IPTp than in those who adhered (24.6% versus 14.3%, respectively; risk ratio
      =2.5; 95% confidence interval 2.1, 3.0; P<0.001). Similarly, neonatal malaria
      occurred significantly more in neonates whose mothers did not receive IPTp
      compared to those whose mothers received at least one dose of IPTp (7.4% versus
      3.4%; risk ratio =1.4; 95% confidence interval 0.9, 2.1; P=0.003). CONCLUSION:
      More than one half of parturients failed to adhere to prescribed intermittent
      preventive treatment for malaria in pregnancy in the major obstetric centers in
      Abakaliki, South East Nigeria. The very high prevalence of malaria among women
      who failed to adhere to IPTp and the associated adverse neonatal outcomes demands
      more pragmatic ways of improving access to, and acceptability of, malaria
      preventive measures in this area.

PMID- 24741296
TI  - A systematic review of interventions conducted in clinical or community settings
      to improve dual-task postural control in older adults.
AB  - BACKGROUND: Injury due to falls is a major problem among older adults. Decrements
      in dual-task postural control performance (simultaneously performing two tasks,
      at least one of which requires postural control) have been associated with an
      increased risk of falling. Evidence-based interventions that can be used in
      clinical or community settings to improve dual-task postural control may help to
      reduce this risk. PURPOSE: THE AIMS OF THIS SYSTEMATIC REVIEW ARE: 1) to identify
      clinical or community-based interventions that improved dual-task postural
      control among older adults; and 2) to identify the key elements of those
      interventions. DATA SOURCES: Studies were obtained from a search conducted
      through October 2013 of the following electronic databases: PubMed, CINAHL,
      PsycINFO, and Web of Science. STUDY SELECTION: Randomized and nonrandomized
      controlled studies examining the effects of interventions aimed at improving dual
      task postural control among community-dwelling older adults were selected. DATA
      EXTRACTION: All studies were evaluated based on methodological quality.
      Intervention characteristics including study purpose, study design, and sample
      size were identified, and effects of dual-task interventions on various postural
      control and cognitive outcomes were noted. DATA SYNTHESIS: Twenty-two studies
      fulfilled the selection criteria and were summarized in this review to identify
      characteristics of successful interventions. LIMITATIONS: The ability to
      synthesize data was limited by the heterogeneity in participant characteristics,
      study designs, and outcome measures. CONCLUSION: Dual-task postural control can
      be modified by specific training. There was little evidence that single-task
      training transferred to dual-task postural control performance. Further
      investigation of dual-task training using standardized outcome measurements is
      needed.

PMID- 24741297
TI  - Relationship between obesity, metabolic syndrome, and nonalcoholic fatty liver
      disease in the elderly agricultural and fishing population of Taiwan.
AB  - BACKGROUND: The purpose of this study was to explore the relationship between
      obesity, the metabolic syndrome, and nonalcoholic fatty liver disease (NAFLD) in
      the elderly agricultural and fishing population of Taipei, Taiwan. METHODS: The
      study participants comprised 6,511 (3,971 male and 2,540 female) healthy elderly
      subjects voluntarily attending a teaching hospital for a physical check-up in
      2010. Blood samples and real-time ultrasound-proven fatty liver sonography
      results were collected. RESULTS: The prevalence of NAFLD in this elderly
      population was 27.2%, including mild NAFLD (16.0%), moderate NAFLD (10.3%), and
      severe NAFLD (0.9%). The prevalence of moderate or severe NAFLD for metabolic
      syndrome proved to be substantially greater (P<0.0001, chi(2) test) for one or
      two metabolic factors. Using multinomial logistic regression analysis, age, sex,
      metabolic syndrome, and higher body mass index had a statistically significant
      association with mild NAFLD. Age, sex, metabolic syndrome, higher body mass
      index, and higher alanine aminotransferase were significantly related to moderate
      NAFLD. In addition, higher body mass index, higher uric acid, and higher alanine
      aminotransferase levels were significantly related to severe NAFLD. The
      sensitivity and specificity of body mass index and waist circumference as markers
      of NAFLD were estimated to be 81% and 84%, respectively, and 77% and 69%,
      respectively. CONCLUSION: The prevalence of mild or moderate NAFLD was related to
      obesity and metabolic syndrome. Higher body mass index was also related to severe
      NAFLD but not to metabolic syndrome. Targeting this population for control of
      obesity and improved metabolic function is important.

PMID- 24741298
TI  - Long-term effects of antihypertensive medications on bone mineral density in men
      older than 55 years.
AB  - INTRODUCTION: In this study, we investigated the effects of long-term
      antihypertensive treatment with calcium channel blockers or beta blockers on the
      bone mineral density of maxilla, as determined by cone-beam computed tomography
      (CBCT). MATERIAL AND METHODS: This retrospective study was conducted on CBCT
      images of men older than 55 years who had received different dental indications.
      Data were grouped into three categories according to the antihypertensive
      medication history of the patients: group A included patients who had been taking
      beta-blocker treatment for more than 5 years, group B included patients who had
      been taking calcium channel blocker treatment for more than 5 years, and the
      control group included patients who had never used any hypertensive medications
      before. RESULTS: Statistically significant differences were observed between the
      beta blocker and calcium channel blocker groups. CONCLUSION: In hypertension
      treatment, beta blockers may be preferred to calcium channel blockers in patients
      at high risk for osteoporosis and bone resorption.

PMID- 24741299
TI  - Long-term results of external valvuloplasty in adult patients with isolated great
      saphenous vein insufficiency.
AB  - OBJECTIVE: The aim of this study is to present our 7-year results of external
      valvuloplasty for isolated great saphenous vein (GSV) insufficiency. METHODS:
      External valvuloplasty was applied in 83 patients with isolated GSV
      insufficiency. Follow-up consisted of venous color duplex scanning performed on
      the first postoperative day, the first postoperative month, and then annually.
      Valvular insufficiency, venous reflux, and venous thrombosis formation in the
      saphenofemoral junction were the main outcomes. RESULTS: A complete clinical and
      radiological healing was observed in 50 patients (60%). In 13 cases (15.6%), a
      secondary surgical treatment was performed consisting of vena saphena magna high
      ligation/stripping and varicose vein excisions, mainly due to severe and
      progressive vena saphena magna valvular insufficiency and clinical persistence of
      symptoms. Eight patients (9.6%) developed superficial vein thrombosis, and only
      one patient (1.2%) developed deep vein thrombosis. Contact was lost from 32
      patients (38.5%) for different reasons. CONCLUSION: External valvuloplasty is an
      effective surgical technique for selected cases of isolated GSV insufficiency
      without extensive varicose dilatations. This alternative method can be safely
      administered as an alternative to high ligation and conventional GSV stripping.

PMID- 24741300
TI  - Reliability of the Serbian version of the International Physical Activity
      Questionnaire for older adults.
AB  - The purpose of this study was to determine the test-retest reliability of the
      International Physical Activity Questionnaire (IPAQ) for older adults in Serbia.
      Six hundred and sixty older adults (352 men, 53%; 308 women, 47%; mean age
      67.65+/-5.76 years) participated in the study. To examine test-retest
      reliability, the participants were asked to complete the IPAQ on two occasions 2
      weeks apart. Moderate reliability was observed between the repeated IPAQ, with
      intraclass correlation coefficients ranging from 0.53 to 0.91. The least
      reliability was established in leisure time activity (0.53) and the most
      reliability in the transport domain (0.91). Men and women had similar intraclass
      correlation coefficients for total physical activity (0.71 versus 0.74,
      respectively), while the biggest difference was obtained for housework in men
      (0.68) and in women (0.90). Our study shows that the long version of the IPAQ is
      a reliable instrument for assessing physical activity levels in older adults and
      that it may be useful for generating internationally comparable data. 

PMID- 24741301
TI  - Clinical issues of mucus accumulation in COPD.

PMID- 24741302
TI  - Targeted nanotherapeutics in cancer.

PMID- 24741303
TI  - Synthesis of ciprofloxacin-conjugated poly (L-lactic acid) polymer for nanofiber
      fabrication and antibacterial evaluation.
AB  - Ciprofloxacin was conjugated with polylactide (PLA) via the secondary amine group
      of the piperazine ring using PLA and 7-(4-(2-Chloroacetyl) piperazin-1-yl)-1
      cyclopropyl-6-fluoro-1, 4-dihydro-4-oxoquinoline-3-carboxylic acid. Zinc
      prolinate, a biocompatible catalyst was synthesized, characterized, and used in
      ring opening polymerization of L-lactide. Five different kinds of OH-terminated
      poly(L-lactide) (two-, three-, four-, six-arm, star-shaped) homopolymers were
      synthesized by ring opening polymerization of L-lactide in the presence of
      dodecanol, glycerol, pentaerythritol, dipentaerythritol as initiator and zinc
      prolinate as a catalyst. The structures of the polymers and conjugates were
      thoroughly characterized by means of gel permeation chromatography, matrix
      assisted laser desorption/ionization - time of flight mass spectrometry, and
      nuclear magnetic resonance spectroscopy. PLA (molecular weight =100,000) and
      ciprofloxacin conjugated PLA were used for fabrication of nonwoven nanofiber mat
      (diameter ranges; 150-400 nm) having pore size (62-102 nm) using electrospinning.
      The microbiological assessment shows that the release of ciprofloxacin possesses
      antimicrobial activity. The drug-release behavior of the mat was studied to
      reveal potential application as a drug delivery system. The result shows that the
      ciprofloxacin release rates of the PLA conjugate nonwoven nanofiber mat could be
      controlled by the drug loading content and the release medium. The development of
      a biodegradable ciprofloxacin system, based on nonwoven nanofiber mat, should be
      of great interest in drug delivery systems. 

PMID- 24741304
TI  - Receptor binding peptides for target-selective delivery of nanoparticles
      encapsulated drugs.
AB  - Active targeting by means of drug encapsulated nanoparticles decorated with
      targeting bioactive moieties represents the next frontier in drug delivery; it
      reduces drug side effects and increases the therapeutic index. Peptides, based on
      their chemical and biological properties, could have a prevalent role to direct
      drug encapsulated nanoparticles, such as liposomes, micelles, or hard
      nanoparticles, toward the tumor tissues. A considerable number of molecular
      targets for peptides are either exclusively expressed or overexpressed on both
      cancer vasculature and cancer cells. They can be classified into three wide
      categories: integrins; growth factor receptors (GFRs); and G-protein coupled
      receptors (GPCRs). Therapeutic agents based on nanovectors decorated with
      peptides targeting membrane receptors belonging to the GPCR family overexpressed
      by cancer cells are reviewed in this article. The most studied targeting membrane
      receptors are considered: somatostatin receptors; cholecystokinin receptors;
      receptors associated with the Bombesin like peptides family; luteinizing hormone
      releasing hormone receptors; and neurotensin receptors. Nanovectors of different
      sizes and shapes (micelles, liposomes, or hard nanoparticles) loaded with
      doxorubicin or other cytotoxic drugs and externally functionalized with natural
      or synthetic peptides are able to target the overexpressed receptors and are
      described based on their formulation and in vitro and in vivo behaviors. 

PMID- 24741305
TI  - Effects of magnetic cobalt ferrite nanoparticles on biological and artificial
      lipid membranes.
AB  - BACKGROUND: The purpose of this work is to provide experimental evidence on the
      interactions of suspended nanoparticles with artificial or biological membranes
      and to assess the possibility of suspended nanoparticles interacting with the
      lipid component of biological membranes. METHODS: 1-Palmitoyl-2-oleoyl-sn-glycero
      3-phosphocholine (POPC) lipid vesicles and human red blood cells were incubated
      in suspensions of magnetic bare cobalt ferrite (CoFe2O4) or citric acid (CA)
      adsorbed CoFe2O4 nanoparticles dispersed in phosphate-buffered saline and glucose
      solution. The stability of POPC giant unilamellar vesicles after incubation in
      the tested nanoparticle suspensions was assessed by phase-contrast light
      microscopy and analyzed with computer-aided imaging. Structural changes in the
      POPC multilamellar vesicles were assessed by small angle X-ray scattering, and
      the shape transformation of red blood cells after incubation in tested
      suspensions of nanoparticles was observed using scanning electron microscopy and
      sedimentation, agglutination, and hemolysis assays. RESULTS: Artificial lipid
      membranes were disturbed more by CA-adsorbed CoFe2O4 nanoparticle suspensions
      than by bare CoFe2O4 nanoparticle suspensions. CA-adsorbed CoFe2O4-CA
      nanoparticles caused more significant shape transformation in red blood cells
      than bare CoFe2O4 nanoparticles. CONCLUSION: Consistent with their smaller sized
      agglomerates, CA-adsorbed CoFe2O4 nanoparticles demonstrate more pronounced
      effects on artificial and biological membranes. Larger agglomerates of
      nanoparticles were confirmed to be reactive against lipid membranes and thus not
      acceptable for use with red blood cells. This finding is significant with respect
      to the efficient and safe application of nanoparticles as medicinal agents.

PMID- 24741306
TI  - Methotrexate diethyl ester-loaded lipid-core nanocapsules in aqueous solution
      increased antineoplastic effects in resistant breast cancer cell line.
AB  - Breast cancer is the most frequent cancer affecting women. Methotrexate (MTX) is
      an antimetabolic drug that remains important in the treatment of breast cancer.
      Its efficacy is compromised by resistance in cancer cells that occurs through a
      variety of mechanisms. This study evaluated apoptotic cell death and cell cycle
      arrest induced by an MTX derivative (MTX diethyl ester [MTX(OEt)2]) and MTX(OEt)2
      loaded lipid-core nanocapsules in two MTX-resistant breast adenocarcinoma cell
      lines, MCF-7 and MDA-MB-231. The formulations prepared presented adequate
      granulometric profile. The treatment responses were evaluated through flow
      cytometry. Relying on the mechanism of resistance, we observed different
      responses between cell lines. For MCF-7 cells, MTX(OEt)2 solution and MTX(OEt)2
      loaded lipid-core nanocapsules presented significantly higher apoptotic rates
      than untreated cells and cells incubated with unloaded lipid-core nanocapsules.
      For MDA-MB-231 cells, MTX(OEt)2-loaded lipid-core nanocapsules were significantly
      more efficient in inducing apoptosis than the solution of the free drug. S-phase
      cell cycle arrest was induced only by MTX(OEt)2 solution. The drug
      nanoencapsulation improved apoptosis induction for the cell line that presents
      MTX resistance by lack of transport receptors. 

PMID- 24741307
TI  - Biosynthesis and characterization of silver nanoparticles using panchakavya, an
      Indian traditional farming formulating agent.
AB  - Synthesis of silver nanoparticles (AgNPs) with biological properties is of vast
      significance in the development of scientifically valuable products. In the
      present study, we describe simple, unprecedented, nontoxic, eco-friendly, green
      synthesis of AgNPs using an Indian traditional farming formulating agent,
      panchakavya. Silver nitrate (1 mM) solution was mixed with panchakavya filtrate
      for the synthesis of AgNPs. The nanometallic dispersion was characterized by
      surface plasmon absorbance measuring 430 nm. Transmission electron microscopy
      showed the morphology and size of the AgNPs. Scanning electron microscopy-energy
      dispersive spectroscopy and X-ray diffraction analysis confirmed the presence of
      AgNPs. Fourier transform infrared spectroscopy analysis revealed that proteins in
      the panchakavya were involved in the reduction and capping of AgNPs. In addition,
      we studied the antibacterial activity of synthesized AgNPs. The synthesized AgNPs
      (1-4 mM) extensively reduced the growth rate of antibiotic resistant bacteria
      such as Aeromonas sp., Acinetobacter sp., and Citrobacter sp., according to the
      increasing concentration of AgNPs. 

PMID- 24741308
TI  - Surface engineered antifouling optomagnetic SPIONs for bimodal targeted imaging
      of pancreatic cancer cells.
AB  - Targeted imaging contrast agents for early pancreatic ductal adenocarcinoma
      diagnosis was developed using superparamagnetic iron oxide nanoparticles
      (SPIONs). For phase transfer of SPIONs, the hydrophobic SPIONs are first treated
      with tetrafluoroborate and then capped by bovine serum albumin (BSA) via ligand
      exchange. It was experimentally found that nitrosyl tetrafluoroborate
      pretreatment and proper structures of molecules are essential to the effective
      surface functionalization of SPIONs. Nonspecific binding was found to be
      significantly reduced by BSA surface functionalized hydrophobic SPIONs
      (BSA.SPIONs). The BSA.SPIONs were monodispersed with an average size of
      approximately 18.0 nm and stable in a wide pH range and various ionic strengths
      even after 7 days of storage. The longitudinal and transverse proton relaxation
      rate (r1, r2) values of the BSA.SPIONs were determined to be 11.6 and 154.2 s(-1)
      per mM of Fe(3+) respectively. The r2/r1 ratio of 13.3 ensured its application as
      the T2-weighted magnetic resonance imaging contrast agents. When conjugated with
      near-infrared fluorescent dye and monoclonal antibody, the (dye)BSA.SPION
      monoclonal antibody bioconjugates showed excellent targeting capability with
      minimal nonspecific binding in the bimodal imaging of pancreatic cancer cells.
      The experimental approach is facile, environmentally benign, and straightforward,
      which presents great promise in early cancer diagnosis. 

PMID- 24741309
TI  - Genetically engineered nanocarriers for drug delivery.
AB  - Cytotoxicity, low water solubility, rapid clearance from circulation, and off
      target side-effects are common drawbacks of conventional small-molecule drugs. To
      overcome these shortcomings, many multifunctional nanocarriers have been proposed
      to enhance drug delivery. In concept, multifunctional nanoparticles might carry
      multiple agents, control release rate, biodegrade, and utilize target-mediated
      drug delivery; however, the design of these particles presents many challenges at
      the stage of pharmaceutical development. An emerging solution to improve control
      over these particles is to turn to genetic engineering. Genetically engineered
      nanocarriers are precisely controlled in size and structure and can provide
      specific control over sites for chemical attachment of drugs. Genetically
      engineered drug carriers that assemble nanostructures including nanoparticles and
      nanofibers can be polymeric or non-polymeric. This review summarizes the recent
      development of applications in drug and gene delivery utilizing nanostructures of
      polymeric genetically engineered drug carriers such as elastin-like polypeptides,
      silk-like polypeptides, and silk-elastin-like protein polymers, and non-polymeric
      genetically engineered drug carriers such as vault proteins and viral proteins. 

PMID- 24741310
TI  - Heat-transfer-based detection of SNPs in the PAH gene of PKU patients.
AB  - Conventional neonatal diagnosis of phenylketonuria is based on the presence of
      abnormal levels of phenylalanine in the blood. However, for carrier detection and
      prenatal diagnosis, direct detection of disease-correlated mutations is needed.
      To speed up and simplify mutation screening in genes, new technologies are
      developed. In this study, a heat-transfer method is evaluated as a mutation
      detection technology in entire exons of the phenylalanine hydroxylase (PAH) gene.
      This method is based on the change in heat-transfer resistance (R(th)) upon
      thermal denaturation of dsDNA (double-stranded DNA) on nanocrystalline diamond.
      First, ssDNA (single-stranded DNA) fragments that span the size range of the PAH
      exons were successfully immobilized on nanocrystalline diamond. Next, it was
      studied whether an R(th) change could be observed during the thermal denaturation
      of these DNA fragments after hybridization to their complementary counterpart. A
      clear R(th) shift during the denaturation of exon 5, exon 9, and exon 12 dsDNA
      was observed, corresponding to lengths of up to 123 bp. Finally, R(th) was shown
      to detect prevalent single-nucleotide polymorphisms, c.473G>A (R158Q), c.932T>C
      (p.L311P), and c.1222C>T (R408W), correlated with phenylketonuria, displaying an
      effect related to the different melting temperatures of homoduplexes and
      heteroduplexes.

PMID- 24741311
TI  - Osteogenic activity of titanium surfaces with nanonetwork structures.
AB  - BACKGROUND: Titanium surfaces play an important role in affecting
      osseointegration of dental implants. Previous studies have shown that the titania
      nanotube promotes osseointegration by enhancing osteogenic differentiation. Only
      relatively recently have the effects of titanium surfaces with other
      nanostructures on osteogenic differentiation been investigated. METHODS: In this
      study, we used NaOH solutions with concentrations of 2.5, 5.0, 7.5, 10.0, and
      12.5 M to develop a simple and useful titanium surface modification that
      introduces the nanonetwork structures with titania nanosheet (TNS) nanofeatures
      to the surface of titanium disks. The effects of such a modified nanonetwork
      structure, with different alkaline concentrations on the osteogenic
      differentiation of rat bone marrow mesenchymal stem cells (BMMSCs), were
      evaluated. RESULTS: The nanonetwork structures with TNS nanofeatures induced by
      alkali etching markedly enhanced BMMSC functions of cell adhesion and
      osteogenesis-related gene expression, and other cell behaviors such as
      proliferation, alkaline phosphatase activity, extracellular matrix deposition,
      and mineralization were also significantly increased. These effects were most
      pronounced when the concentration of NaOH was 10.0 M. CONCLUSION: The results
      suggest that nanonetwork structures with TNS nanofeatures improved BMMSC
      proliferation and induced BMMSC osteogenic differentiation. In addition, the
      surfaces formed with 10.0 M NaOH suggest the potential to improve the clinical
      performance of dental implants.

PMID- 24741312
TI  - Nanoparticle-based drug delivery to improve the efficacy of antiretroviral
      therapy in the central nervous system.
AB  - Antiretroviral drug therapy plays a cornerstone role in the treatment of human
      immunodeficiency virus (HIV)/acquired immunodeficiency syndrome patients. Despite
      obvious advances over the past 3 decades, new approaches toward improved
      management of infected individuals are still required. Drug distribution to the
      central nervous system (CNS) is required in order to limit and control viral
      infection, but the presence of natural barrier structures, in particular the
      blood-brain barrier, strongly limits the perfusion of anti-HIV compounds into
      this anatomical site. Nanotechnology-based approaches may help providing
      solutions for antiretroviral drug delivery to the CNS by potentially prolonging
      systemic drug circulation, increasing the crossing and reducing the efflux of
      active compounds at the blood-brain barrier, and providing cell/tissue-targeting
      and intracellular drug delivery. After an initial overview on the basic features
      of HIV infection of the CNS and barriers to active compound delivery to this
      anatomical site, this review focuses on recent strategies based on antiretroviral
      drug-loaded solid nanoparticles and drug nanosuspensions for the potential
      management of HIV infection of the CNS. 

PMID- 24741313
TI  - An in vitro evaluation of graphene oxide reduced by Ganoderma spp. in human
      breast cancer cells (MDA-MB-231).
AB  - BACKGROUND: Recently, graphene and graphene-related materials have attracted much
      attention due their unique properties, such as their physical, chemical, and
      biocompatibility properties. This study aimed to determine the cytotoxic effects
      of graphene oxide (GO) that is reduced biologically using Ganoderma spp. mushroom
      extracts in MDA-MB-231 human breast cancer cells. METHODS: Herein, we describe a
      facile and green method for the reduction of GO using extracts of Ganoderma spp.
      as a reducing agent. GO was reduced without any hazardous chemicals in an aqueous
      solution, and the reduced GO was characterized using a range of analytical
      procedures. The Ganoderma extract (GE)-reduced GO (GE-rGO) was characterized by
      ultraviolet-visible absorption spectroscopy, X-ray diffraction, Fourier-transform
      infrared spectroscopy, X-ray photoelectron spectroscopy, dynamic light
      scattering, scanning electron microscopy, Raman spectroscopy, and atomic force
      microscopy. Furthermore, the toxicity of GE-rGO was evaluated using a sequence of
      assays such as cell viability, lactate dehydrogenase leakage, and reactive oxygen
      species generation in human breast cancer cells (MDA-MB-231). RESULTS: The
      preliminary characterization of reduction of GO was confirmed by the red-shifting
      of the absorption peak for GE-rGO to 265 nm from 230 nm. The size of GO and GE
      rGO was found to be 1,880 and 3,200 nm, respectively. X-ray diffraction results
      confirmed that reduction processes of GO and the processes of removing
      intercalated water molecules and the oxide groups. The surface functionalities
      and chemical natures of GO and GE-rGO were confirmed using Fourier-transform
      infrared spectroscopy and X-ray photoelectron spectroscopy. The surface
      morphologies of the synthesized graphene were analyzed using high-resolution
      scanning electron microscopy. Raman spectroscopy revealed single- and multilayer
      properties of GE-rGO. Atomic force microscopy images provided evidence for the
      formation of graphene. Furthermore, the effect of GO and GE-rGO was examined
      using a series of assays, such as cell viability, membrane integrity, and
      reactive oxygen species generation, which are key molecules involved in
      apoptosis. The results obtained from cell viability and lactate dehydrogenase
      assay suggest that GO and GE-rGO cause dose-dependent toxicity in the cells.
      Interestingly, it was found that biologically derived GE-rGO is more toxic to
      cancer cells than GO. CONCLUSION: We describe a simple, green, nontoxic, and cost
      effective approach to producing graphene using mushroom extract as a reducing and
      stabilizing agent. The proposed method could enable synthesis of graphene with
      potential biological and biomedical applications such as in cancer and angiogenic
      disorders. To our knowledge, this is the first report using mushroom extract as a
      reducing agent for the synthesis of graphene. Mushroom extract can be used as a
      biocatalyst for the production of graphene.

PMID- 24741314
TI  - Chorea disclosing a polycythemia vera.
AB  - Chorea is a rare complication of polycythemia. We report the case of a 70 year
      old woman whose polycythemia vera (PV), with Janus Kinase-2 (JAK2) mutation,
      presented as chorea. Chorea resolved quickly after hydroxyurea therapy. 

PMID- 24741315
TI  - Multifocal motor neuropathy: a review of pathogenesis, diagnosis, and treatment.
AB  - Multifocal motor neuropathy (MMN) is an uncommon, purely motor neuropathy
      associated with asymmetric deficits with predilection for upper limb involvement.
      Even in the early descriptions of MMN, the associations of anti-GM1 antibodies
      and robust response to immunomodulatory treatment were recognized. These features
      highlight the likelihood of an underlying autoimmune etiology of MMN. The
      clinical presentation of MMN can closely mimic several neurological conditions
      including those with more malignant prognoses such as motor neuron disease.
      Therefore early and rapid recognition of MMN is critical. Serological evidence of
      anti GM-1 antibodies and electrodiagnostic findings of conduction block are
      helpful diagnostic clues for MMN. Importantly, these diagnostic features are not
      universally present, and patients lacking these characteristic findings can
      demonstrate similar robust response to immunodulatory treatment. In the current
      review, recent research in the areas of diagnosis, pathogenesis, and treatment of
      MMN and needs for the future are discussed. The characteristic findings of MMN
      and treatment implications are reviewed and contrasted with other mimicking
      disorders. 

PMID- 24741316
TI  - Utilizing buprenorphine-naloxone to treat illicit and prescription-opioid
      dependence.
AB  - OBJECTIVES: To review current evidence on buprenorphine-naloxone (bup/nx) for the
      treatment of opioid-use disorders, with a focus on strategies for clinical
      management and office-based patient care. QUALITY OF EVIDENCE: Medline and the
      Cochrane Database of Systematic Reviews were searched. Consensus reports,
      guidelines published, and other authoritative sources were also included in this
      review. Apart from expert guidelines, data included in this review constitute
      level 1 evidence. FINDINGS: Bup/nx is a partial MU-opioid agonist combined with
      the opioid antagonist naloxone in a 4:1 ratio. It has a lower abuse potential,
      carries less stigma, and allows for more flexibility than methadone. Bup/nx is
      indicated for both inpatient and ambulatory medically assisted withdrawal (acute
      detoxification) and long-term substitution treatment (maintenance) of patients
      who have a mild-to-moderate physical dependence. A stepwise long-term
      substitution treatment with regular monitoring and follow-up assessment is
      usually preferred, as it has better outcomes in reducing illicit opioid use,
      minimizing concomitant risks such as human immunodeficiency virus and hepatitis C
      transmission, retaining patients in treatment and improving global functioning.
      CONCLUSION: Bup/nx is safe and effective for opioid detoxification and
      substitution treatment. Its unique pharmaceutical properties make it particularly
      suitable for office-based maintenance treatment of opioid-use disorder.

PMID- 24741317
TI  - Comparative review of the blood pressure-lowering and cardiovascular benefits of
      telmisartan and perindopril.
AB  - Hypertension is a major cardiovascular (CV) risk factor, and blood pressure (BP)
      lowering treatment substantially reduces the risk. This review compares the
      available clinical evidence from the BP-lowering and CV-outcome studies of
      telmisartan and perindopril, which are among the most intensively studied members
      of their respective classes. The PubMed database was searched for telmisartan and
      perindopril publications meeting the following criteria: 1) head-to-head
      comparison trials for BP lowering; and 2) CV-outcome studies (ie, ones with a CV
      event, mortality, or hospitalization outcome) in patients with CV risk factors
      but without heart failure. In comparative trials, telmisartan treatment resulted
      in significantly higher reduction in trough BP and mean ambulatory diastolic BP
      for the last 8 hours of the dosing interval compared with perindopril. In mainly
      placebo-controlled CV-outcome studies in patients with hypertension, CV benefits
      with perindopril were associated with large reductions in BP. There were no CV
      outcome studies with telmisartan in patients with hypertension. The beyond-BP
      lowering CV-protective benefits of telmisartan were demonstrated in the active
      controlled ONTARGET (ONgoing Telmisartan Alone and in combination with Ramipril
      Global Endpoint Trial) trial, which included patients with controlled BP at
      baseline. In general, the trials discussed in this review reinforce the fact that
      perindopril and telmisartan are two long-acting antihypertensive drugs that
      reduce BP over 24 hours, and are the best-evidenced drugs in their class with
      proven CV protection. It is also clear that the benefits are not a "class
      effect", and vary between the different drugs within each class. Hence, the best
      approach for treatments tailored to individual patient needs should be evidence
      based specific drugs, rather than a drug-class recommendation for achieving
      therapeutic targets. 

PMID- 24741318
TI  - Gastrointestinal ulcers, role of aspirin, and clinical outcomes: pathobiology,
      diagnosis, and treatment.
AB  - Peptic ulcer disease is a major cause of morbidity and mortality in the US with
      more than six million diagnoses annually. Ulcers are reported as the most common
      cause of hospitalization for upper gastrointestinal (GI) bleeding and are often a
      clinical concern due to the widespread use of aspirin and nonsteroidal anti
      inflammatory drugs, both of which have been shown to induce ulcer formation. The
      finding that Helicobacter pylori infection (independent of aspirin use) is
      associated with the development of ulcers led to a more thorough understanding of
      the causes and pathogenesis of ulcers and an improvement in therapeutic options.
      However, many patients infected with H. pylori are asymptomatic and remain
      undiagnosed. Complicating matters is a current lack of understanding of the
      association between aspirin use and asymptomatic ulcer formation. Low-dose
      aspirin prescriptions have increased, particularly for cardioprotection.
      Unfortunately, the GI side effects associated with aspirin therapy continue to be
      a major complication in both symptomatic and asymptomatic patients. These safety
      concerns should be important considerations in the decision to use aspirin and
      warrant further education. The medical community needs to continue to improve
      awareness of aspirin-induced GI bleeding to better equip physicians and improve
      care for patients requiring aspirin therapy. 

PMID- 24741319
TI  - Micro-ribonucleic acid expression profiling and bioinformatic target gene
      analyses in laryngeal carcinoma.
AB  - Abnormal expression of micro-ribonucleic acid (miRNA) might be clinically
      valuable as a biomarker or treatment target in the early diagnosis, treatment,
      and prognosis of tumors. However, little is known concerning abnormal miRNA
      expression of laryngeal carcinoma, one of the most commonly encountered head and
      neck tumors. Microarray analysis was used to obtain miRNA-expression profiles of
      ten pairs of freshly frozen laryngeal carcinoma tissue and surrounding normal
      tissue specimens. Characteristic miRNAs that were significantly related to
      laryngeal carcinoma were identified. Verification was performed using an
      additional 32 pairs of samples. The expression of two miRNAs (miR-21-3p and miR
      106b-3p) was upregulated in both microarray and quantitative real-time polymerase
      chain-reaction analyses, whereas the expression of six miRNAs (let-7f-5p, miR-10a
      5p, miR-125a-5p, miR-144-3p, miR-195-5p, and miR-203) was downregulated. The
      decreased expression of let-7f-5p and miR-195-5p is a novel finding in head and
      neck cancer. The target genes of these miRNAs were also predicted through
      multiple software programs. The differential expression of miRNAs might be
      related to the early onset and development of laryngeal carcinoma, and may be
      exploited as new biomarkers and therapeutic targets in the treatment of laryngeal
      carcinoma. 

PMID- 24741320
TI  - Three-dimensional quantitative structure-activity relationship and docking
      studies in a series of anthocyanin derivatives as cytochrome P450 3A4 inhibitors.
AB  - The cytochrome P450 (CYP)3A4 enzyme affects the metabolism of most drug-like
      substances, and its inhibition may influence drug safety. Modulation of CYP3A4 by
      flavonoids, such as anthocyanins, has been shown to inhibit the mutagenic
      activity of mammalian cells. Considering the previous investigations addressing
      CYP3A4 inhibition by these substances, we studied the three-dimensional
      quantitative structure-activity relationship (3D-QSAR) in a series of anthocyanin
      derivatives as CYP3A4 inhibitors. For the training dataset (n=12), comparative
      molecular field analysis (CoMFA) and comparative molecular similarity index
      analysis (CoMSIA) yielded crossvalidated and non-crossvalidated models with a q
      (2) of 0.795 (0.687) and r (2) of 0.962 (0.948), respectively. The models were
      also validated by an external test set of four compounds with r (2) of 0.821
      (CoMFA) and r (2) of 0.812 (CoMSIA). The binding affinity modes associated with
      experimentally derived IC50 (half maximal inhibitory concentration) values were
      confirmed by molecular docking into the CYP3A4 active site with r (2) of 0.66.
      The results obtained from this study are useful for a better understanding of the
      effects of anthocyanin derivatives on inhibition of carcinogen activation and
      cellular DNA damage. 

PMID- 24741321
TI  - Economic evaluation of aclidinium bromide in the management of moderate to severe
      COPD: an analysis over 5 years.
AB  - PURPOSE: Aclidinium bromide is a long-acting muscarinic antagonistic used in
      maintenance treatment of chronic obstructive pulmonary disease (COPD). A model
      based health economic study evaluated the cost-effectiveness of aclidinium 400
      MUg bid as an alternative to tiotropium 18 MUg od for this indication in the US.
      PATIENTS AND METHODS: PATIENT CHARACTERISTICS IN THIS MODEL REFLECT THOSE IN THE
      ACLIDINIUM CLINICAL STUDIES: age >40 years, stable moderate-to-severe COPD,
      current or ex-smokers (>10 pack-years), post-salbutamol forced expiratory volume
      in 1 second (FEV1) >=30% and <80% of predicted normal value, and FEV1/forced
      vital capacity <70%. The model consists of five main health states indicating
      severity of COPD and the level of utility, resource use, and costs. Treatment
      efficacy over 5 years was modeled using FEV1% predicted; a network meta-analysis
      comparing aclidinium and tiotropium was used to estimate disease progression
      during the first 24 weeks, and results from the UPLIFT trial were used for time
      points after 24 weeks. Quality of life was assessed using utility scores in US
      patients from the UPLIFT trial. Cost-effectiveness was assessed as the
      incremental cost per quality-adjusted life year (QALY) gained. RESULTS: Over 5
      years, QALYs were 3.50 for aclidinium versus 3.49 for tiotropium; life years
      accumulated were 4.52 for both. In this economic model, aclidinium versus
      tiotropium showed marginally fewer exacerbations (3.364 versus 3.390,
      respectively) and mean total health care costs (US$126,274 versus US$128,591,
      respectively). In all scenario analyses performed (discount factors of 0% and 6%
      for benefits and costs; time horizon of 1 year; mapping St George's Respiratory
      Questionnaire to European Quality of Life-5 Dimensions; excluding pharmacy costs,
      COPD-related cost only; cost of exacerbations; including ACCORD II trial in the
      network meta-analysis), aclidinium was associated with lower costs and marginally
      greater QALYs versus tiotropium. CONCLUSION: Aclidinium is potentially cost
      effective compared with tiotropium for maintenance treatment of moderate-to
      severe COPD.

PMID- 24741322
TI  - A challenging diagnosis: case report of extensive pyoderma gangrenosum at
      multiple sites.
AB  - BACKGROUND: Pyoderma gangrenosum (PG) is a rare dermatological condition
      characterized by the rapid progression of a painful, necrolytic ulcer with an
      irregular, undermined border and commonly affects the lower extremities, mainly
      in the pretibial area. The diagnosis of PG is not easy. Due to lack of diagnostic
      laboratory test and histopathological findings indicative of PG, it is often
      misdiagnosed as an infection. This results in delayed or inappropriate treatment
      of the condition, which leads to devastating consequences such as limb amputation
      and death. MAIN OBSERVATIONS: We report a rare case of a 51-year-old female who
      was initially diagnosed as having infected ulcers and underwent serial
      debridements, which resulted in extensive PG at three different sites (abdominal,
      left thigh, and sacral). CONCLUSION: This case highlights the challenges in
      diagnosing PG, emphasizes the key clinical features to aid diagnosis, and the
      clinical consequences of delayed or misdiagnosis of this condition.

PMID- 24741323
TI  - Submucosal tunneling techniques: current perspectives.
AB  - Advances in endoscopic submucosal dissection include a submucosal tunneling
      technique, involving the introduction of tunnels into the submucosa. These
      tunnels permit safer offset entry into the peritoneal cavity for natural orifice
      transluminal endoscopic surgery. Technical advantages include the visual
      identification of the layers of the gut, blood vessels, and subepithelial tumors.
      The creation of a mucosal flap that minimizes air and fluid leakage into the
      extraluminal cavity can enhance the safety and efficacy of surgery. This
      submucosal tunneling technique was adapted for esophageal myotomy, culminating in
      its application to patients with achalasia. This method, known as per oral
      endoscopic myotomy, has opened up the new discipline of submucosal endoscopic
      surgery. Other clinical applications of the submucosal tunneling technique
      include its use in the removal of gastrointestinal subepithelial tumors and
      endomicroscopy for the diagnosis of functional and motility disorders. This
      review suggests that the submucosal tunneling technique, involving a mucosal
      safety flap, can have potential values for future endoscopic developments. 

PMID- 24741324
TI  - Long-term efficacy and safety of otilonium bromide in the management of irritable
      bowel syndrome: a literature review.
AB  - Irritable bowel syndrome (IBS) is a very common functional gastrointestinal
      disorder characterized by abdominal pain or discomfort and altered bowel habits.
      The disease affects a large part of the world population. The clinical course is
      mostly characterized by a cyclic recurrence of symptoms. Therefore, IBS patients
      should receive, as an initial therapeutic approach, a short course of treatment,
      and long-term treatment should be reserved for those patients with recurrent
      symptoms. The available clinical trials show that significant improvement of the
      symptoms over placebo could be achieved with various drugs, although this
      improvement is frequently time dependent and with high relapse rates after the
      cessation of the treatment. In a proportion of patients, clinically obvious
      relapse could appear long after stopping the treatment. Some of the available
      pharmacologic agents, including otilonium bromide (OB), are able to significantly
      prolong the time to the appearance of relapse, compared with placebo. As a
      consequence, some authors suggest that a cyclic treatment could be of benefit.
      Antispasmodic drugs have been used for many years in an effort to control the
      symptoms of IBS. OB is a poorly absorbed spasmolytic drug, exerting significantly
      greater control of the symptoms of IBS compared with placebo. Recent data suggest
      that the drug could effectively be used for the long-term management of patients
      with IBS. The aim of this review is to provide the reader with an evidence-based
      overview of the efficacy and tolerability of OB in the long-term management of
      IBS patients, based on the results of the clinical trials published so far. 

PMID- 24741326
TI  - A randomized, placebo-controlled, four-period crossover, definitive QT study of
      the effects of APF530 exposure, high-dose intravenous granisetron, and
      moxifloxacin on QTc prolongation.
AB  - BACKGROUND: Regulatory concern about potential QT-interval prolongation by
      serotonin-receptor antagonist antiemetics prompted product-label changes. The
      first-generation serotonin-receptor antagonist granisetron is available in oral
      (PO), intravenous (IV), and transdermal formulations. APF530 is a formulation
      that provides sustained release of granisetron when administered as a single
      subcutaneous (SC) injection. The Phase I study reported here evaluated effects of
      APF530 on electrocardiographic intervals. METHODS: This single-site, double
      blind, placebo-controlled, four-period crossover trial randomized healthy men and
      women to receive varying sequences of APF530 1 g SC, granisetron 50 MUg/kg IV,
      moxifloxacin 400 mg PO, and placebo. Subjects were assessed for 49 hours after
      each treatment. The primary objective was to evaluate differences between
      baseline-adjusted, heart rate-corrected QT-interval change using the Fridericia
      rate correction (dQTcF) for APF530 1 g SC and placebo. Electrocardiograms were
      performed at various times throughout the assessment period. Pharmacokinetics and
      safety were evaluated. RESULTS: The upper one-sided 95% confidence interval (CI)
      for mean baseline-adjusted dQTcF at each post-dose time point between APF530 and
      placebo excluded 10 ms, indicating that APF530 1 g SC had no clinically
      significant effect on QTcF. Maximum observed QTcF change was 4.15 ms (90% CI,
      0.94 to 7.36) at Hour 3. No clinically significant changes in other
      electrocardiogram intervals were observed. APF530 SC pharmacokinetics were as
      expected, with slow absorption (maximum plasma concentration 35.8 ng/mL, median
      time to maximum plasma concentration 11.1 hours) and slow elimination (mean half
      life 18.6 hours; systemic clearance 20.2 L/hour) of granisetron versus the
      expected early peak concentration and elimination of granisetron IV. APF530 SC
      was well tolerated. Adverse events, most commonly constipation and SC injection
      site reactions, were generally mild and quickly resolved. CONCLUSION: APF530 1 g
      SC did not induce clinically significant QTcF interval prolongation or changes in
      the other electrocardiogram intervals, and was well tolerated at twice the
      recommended dose.

PMID- 24741325
TI  - TGF-beta Mediated Crosstalk Between Malignant Hepatocyte and Tumor
      Microenvironment in Hepatocellular Carcinoma.
AB  - In this article, we have reviewed current literature regarding the regulation of
      hepatocellular carcinoma (HCC) by the interaction of malignant hepatocytes and
      their tissue environment through cytokine signaling, here represented by
      transforming growth factor-beta (TGF-beta) signaling. We have discussed responses
      of TGF-beta signaling in transition of hepatic stellate cells to myofibroblasts
      (MFBs), recruitment of tumor-associated macrophages (TAMs), and enrichment of
      tumor-associated endothelial cells (TECs). The malignant hepatocytes also secrete
      various factors such as platelet-derived growth factors (PDGFs), vascular
      endothelial growth factor (VEGF), and TGF-beta. TGF-beta, a super-family of
      cytokines, creates tumor microenvironment by interacting through other growth
      factors (epidermal growth factor receptor (EGFR), PDGF, fibroblast growth factor
      (FGF), hepatocyte growth factor (HGF), VEGF), cytokines and chemokines, and
      extracellular matrix (ECM) remodeling. Hence, the HCC tumor microenvironment may
      now be recognized as an important participant of tumor progression to act as
      potential target to systemic therapies compared to targeted therapies. 

PMID- 24741327
TI  - Cigarette smoking and colorectal cancer mortality among 602,242 Norwegian males
      and females.
AB  - BACKGROUND: Colorectal cancer (CRC) is one of the main cancer types, with high
      incidence and mortality in Norway. We examined the association between different
      measures of smoking exposure and CRC mortality overall and by subsite in a large
      Norwegian cohort. METHODS: We followed 602,242 participants from four Norwegian
      health surveys, aged 19-67 years at enrollment between 1972 and 2003 by linkage
      to the national registries through December 2007. We used Cox proportional hazard
      models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) by
      smoking categories for different CRC endpoints. RESULTS: During a mean follow-up
      of 14 years, 2,333 Norwegian males and females died of CRC (60% men). Male and
      female ever smokers had a 20% (HR 1.23, CI 1.08-1.40 and HR 1.22, 95% CI 1.06
      1.40, respectively) increased risk of death from CRC compared with sex-specific
      never smokers. For proximal colon cancer mortality, female ever smokers had a 50%
      (HR 1.49, 95% CI 1.20-1.87) increased risk compared with female never smokers.
      The increased risk of rectal cancer mortality was about 40% higher for male ever
      smokers (HR 1.43, 95% CI 1.14-1.81) compared with male never smokers. A test for
      heterogeneity by sex showed an increased risk of rectal cancer mortality among
      men which was significant for former smokers (Wald chi(2) =0.02) and an increased
      risk of proximal colon cancer mortality among women which was significant for
      ever and former smokers (Wald chi(2) =0.02 and chi(2) =0.04, respectively).
      CONCLUSION: Smoking is associated with increased CRC mortality in both sexes. The
      risk of rectal and proximal colon cancer mortality was most pronounced among male
      and female smokers respectively.

PMID- 24741328
TI  - Potential drug-drug interactions in HIV-infected children on antiretroviral
      therapy in Lagos, Nigeria.
AB  - BACKGROUND: Multi-therapy is common in HIV-infected children, and the risk for
      clinically significant drug interactions (CSDIs) is high. We investigated the
      prevalence of CSDIs between antiretroviral (ARV) and co-prescribed drugs for
      children attending a large HIV clinic in Lagos, Nigeria. METHODS: The case files
      of pediatric patients receiving treatment at the HIV clinic of the Lagos
      University Teaching Hospital (LUTH), Idi-Araba, between January 2005 and December
      2010 were reviewed. The ARV and co-prescribed drug pairs were evaluated for
      potential interactions using the Liverpool HIV Pharmacology Group website. The
      potential interactions were rated as A (no known interaction), B (minor/no action
      needed), C (moderate/monitor therapy), D (major/therapy modification), and X
      (contraindicated/avoid combination). RESULTS: Of the 310 cases reviewed, 208
      (67.1%) patients were at risk of CSDIs. Artemisinin-based combination therapy was
      prescribed for over one-half of the patients, accounting for 40% of the CSDIs.
      Excluding this drug class, the prevalence of CSDIs reduced from 67.1% to 18.7% in
      58 patients. Most of the CSDIs (579; 97.2%) were moderately significant and
      frequently involved nevirapine and fluconazole (58; 9.7%), zidovudine and
      fluconazole (55; 9.2%), zidovudine and rifampicin (35; 5.9%), and nevirapine and
      prednisolone (31; 5.2%). Age (P=0.392), sex (P=0.783), and moderate (P=0.632) or
      severe (P=0.755) malnutrition were not associated with risk for CSDIs.
      CONCLUSION: There is a tendency for CSDIs between ARV and co-prescribed drugs
      among the group of children evaluated in this study. Measures are necessary to
      prevent important drug interactions and to manage those that are unavoidable.

PMID- 24741329
TI  - Soy isoflavone intake and the likelihood of ever becoming a mother: the Adventist
      Health Study-2.
AB  - OBJECTIVES: As little is known about the possible relationship between the intake
      of phytoestrogens and female fertility, we investigated the relationship between
      soy isoflavone intake and the risk of nulliparity and nulligravidity. METHODS: A
      cross-sectional study of 11,688 North American Adventist women aged 30-50 years
      old with data regarding childbearing. These women were, as a group, characterized
      by a high proportion (54%) of vegetarians and a healthy lifestyle with a very low
      prevalence of smoking and alcohol use. RESULTS: The mean isoflavone intake (17.9
      mg per day) was very high compared to other Western populations. Only 6% of the
      women indicated no intake of isoflavones. We found, after adjustment for age,
      marital status, and educational level, an inverse relationship (P=0.05) between
      isoflavone intake and the likelihood of ever having become a mother. In women
      with high (>=40 mg/day) isoflavone intake (12% of this group of women), the
      adjusted lifetime probability of giving birth to a live child was reduced by
      approximately 3% (95% CI: 0, 7) compared to women with low (<10 mg/day) intake.
      No relationships were found between the isoflavone intake and parity or age at
      first delivery in parous women. A similar inverse relationship (P=0.03) was found
      between the isoflavone intake and the risk of nulligravidity with a 13% (95% CI:
      2, 26) higher risk of never have been pregnant in women with high (>=40 mg/day)
      isoflavone intake. These relationships were found mainly in women who reported
      problems becoming pregnant. CONCLUSION: The findings suggest that a high dietary
      isoflavone intake may have significant impact on fertility.

PMID- 24741330
TI  - Magnetic resonance imaging features of brain and spinal cord injury in a fatal
      case of isopropanol intoxication.
AB  - A 60-year-old man presented with headache, dizziness, and disorientation one day
      after consumption of isopropanol along with ethanol. Computed tomography (CT) of
      the brain performed immediately was unremarkable. The patient collapsed within
      the hospital 30 minutes after the CT scan was done, and remained comatose until
      death, showing no improvement with symptomatic treatment. Magnetic resonance
      imaging of the brain and spine done 6 days after admission revealed bilaterally
      symmetrical hyperintensities involving the cerebral and cerebellar cortex and
      white matter, basal ganglia, thalami, and brainstem on T2-weighted, fluid
      attenuated inversion recovery and diffusion weighted images; similar
      hyperintensities were seen involving the swollen and edematous cervical spinal
      cord and cerebellar tonsillar herniation compressing the proximal cervical cord.
      Petechial hemorrhages were also noted within the brainstem. These features are
      compatible with toxic injury to the brain and cervical spinal cord. To our
      knowledge, the magnetic resonance imaging features of brain and spinal cord
      injury and cerebellar tonsillar herniation, secondary to isopropanol intoxication
      have not been reported in the published literature before. 

PMID- 24741331
TI  - Keratitis-ichthyosis-deafness syndrome: first affected family reported in the
      Middle East.
AB  - INTRODUCTION: Keratitis-ichthyosis-deafness (KID) syndrome is a rare congenital
      multisystem disorder affecting certain tissues of ectodermal origin such as
      epidermis, cochlea, and cornea, leading mainly to palmoplantar hyperkeratosis,
      ichthyosiform scaling, deafness, and blindness. The author reports for the first
      time in the Middle East three family members suffering from KID syndrome in the
      southwestern part of Saudi Arabia. CASE PRESENTATION: Three patients from one
      family (ages 26, 16, and 14 years) of apparently normal parents, with the two
      eldest being females and the youngest being male. All three patients were
      referred from a peripheral hospital to our dermatology clinic due to recurrent
      cutaneous fungal infections on their trunk, forearms, legs, and nails. On full
      assessment, they also found to have nearly similar cutaneous problems manifested
      by palmoplantar hyperkeratosis, generalized ichthyosiform scaling, subungual
      hyperkeratosis, and nail dystrophies. All patients suffered from total hearing
      loss in both ears since childhood as confirmed by pure tune audiometry. However,
      there was no blindness in any case; blepharitis with marked photophobia was the
      only ocular complaint. All these features are classically suggestive of KID
      syndrome.

PMID- 24741332
TI  - Never neglect the atmospheric pressure effect on a brain with a skull defect.
AB  - Herein, we report an unusual case of a patient who presented with a severe,
      sinking skin flap after a decompressive craniectomy and ventriculoperitoneal
      shunt surgery due to a traumatic brain injury. After cranioplasty, the patient's
      neurological deficiency improved and was confirmed by transcranial Doppler
      sonography. In addition to discussing the pathogenesis of the sinking skin flap,
      we emphasize the importance of cranioplasty for neurological improvement and
      remind the surgeon to "never neglect the atmospheric pressure effect on a brain
      with a skull defect". 

PMID- 24741333
TI  - Unexpected difficult airway with hypogonadotropic hypogonadism.
AB  - BACKGROUND: A critical aspect of safe general anesthesia is providing adequate
      ventilation and oxygenation. Failed endotracheal intubation and inadequate
      ventilation with insufficient oxygenation may lead to serious complications, even
      death. Anesthesiologists rarely encounter unexpected difficult airway problems in
      daily routine. Management of an unexpectedly difficult airway consists of
      laryngeal mask ventilation, gum-elastic bougie and video laryngoscopy-assisted
      intubation. Gum-elastic bougie is the easiest and cheapest tool used in case of
      an unexpected difficult intubation occurring in the operating room. CASE: A 53
      year-old male patient with hypogonadotropic hypogonadism presented as an
      unexpected difficult intubation after the induction of anesthesia. No
      pathological finding or predictor of difficult intubation was present. In
      addition, bag-mask ventilation was poor and inadequate. The patient was finally
      successfully intubated with a gum-elastic bougie. CONCLUSION: A difficult airway
      has been described in patients with a variety of endocrine disorders, including
      pituitary diseases, but not with hypogonadism. There may be an unrevealed
      relationship between hypogonadism and difficult airway. Gum-elastic bougie is
      still the most attainable and effective tool in the operation room in this
      situation.

PMID- 24741335
TI  - Glibenclamide in patients with poorly controlled type 2 diabetes: a 12-week,
      prospective, single-center, open-label, dose-escalation study.
AB  - BACKGROUND: The purpose of this study was to investigate the effect of
      glibenclamide dose escalation on blood glucose and insulin in patients with
      poorly controlled type 2 diabetes. METHODS: Twenty-two subjects with type 2
      diabetes were administered increasing doses (0, 2.5, 5, 10, and 20 mg/day) of
      glibenclamide at 2-week intervals. Glibenclamide, glucose, and insulin
      determinations were performed. RESULTS: The decrease in mean blood glucose from
      zero dose was 20%, 22%, 26%, and 28% for doses of 2.5, 5, 10, and 20 mg/day,
      respectively, which was significant from zero dose to 2.5 mg/day (P<=0.001).
      There were no significant decreases in glucose concentration beyond 2.5 mg/day.
      The percentage increase in mean insulin from zero dose was 51%, 58%, 44%, and 33%
      for 2.5, 5, 10, and 20 mg/day respectively. Mean blood insulin increased
      significantly from zero dose to 2.5 mg/day (P<=0.001). There were no significant
      increases in mean insulin concentration beyond 2.5 mg/day. CONCLUSION: The
      results of this study suggest that increasing doses of glibenclamide do not
      produce a proportional increase in insulin secretion or a proportional decrease
      in blood glucose concentration.

PMID- 24741336
TI  - Apnea-hypopnea index: time to wake up.
AB  - Despite the widespread use of the apnea-hypopnea index in research, its
      scientific and statistical properties have not been examined thoroughly. The
      index may be viewed either as a rate (number of events per hour of sleep) or as a
      ratio of two variables (number of events/number of hours of sleep). When
      considered as a rate, the apnea-hypopnea index may be modeled as the dependent
      variable, provided that researchers explicitly state which physical property they
      assume to be measuring. On the other hand, the index is rarely, if ever, the
      preferred model of exposure to sleep-disordered breathing (an independent
      variable), regardless of whether it is considered a rate or a ratio variable.
      Continued indiscriminate use of the apnea-hypopnea index in sleep research should
      be discouraged. 

PMID- 24741337
TI  - Long-term safety and efficacy of natalizumab in relapsing-remitting multiple
      sclerosis: impact on quality of life.
AB  - Natalizumab was the first monoclonal antibody to be approved for the treatment of
      relapsing-remitting multiple sclerosis (RRMS) based on its short-term efficacy
      and overall tolerability. However, the incidence of treatment-associated
      progressive multifocal leukoencephalopathy (PML), an infection of the brain
      caused by the John Cunningham virus, jeopardized this efficacious treatment from
      the beginning. Eight years after licensing of natalizumab, long-term studies
      confirm the considerable and sustained efficacy of natalizumab, although the PML
      complication still threatens one of the most successful treatments available for
      RRMS. During these years, considerable progress has been made in identification
      of risk factors that allow more effective management of PML risk. In addition,
      long-term studies to define better when to start or stop treatment and to
      optimize treatment strategies after cessation of natalizumab are ongoing, and
      hopefully will improve management and will allow natalizumab to remain as a
      valuable therapeutic option for patients with highly active RRMS. 

PMID- 24741338
TI  - Differential expression of cysteine dioxygenase 1 in complex karyotype
      liposarcomas.
AB  - Altered cysteine dioxygenase 1 (CDO1) gene expression has been observed in
      several cancers but has not yet been investigated in liposarcomas. The aim of
      this study was to evaluate CDO1 expression in a cohort of liposarcomas and to
      determine its association with clinicopathological features. Existing microarray
      data indicated variable CDO1 expression in liposarcoma subtypes. CDO1 mRNA from a
      larger cohort of liposarcomas was quantified by real time-PCR, and CDO1 protein
      expression was determined by immunohistochemistry (IHC) in more than 300 tumor
      specimens. Well-differentiated liposarcomas (WDLSs) had significantly higher CDO1
      gene expression and protein levels than dedifferentiated liposarcomas (DDLSs) (P
      < 0.001). Location of the tumor was not predictive of the expression level of
      CDO1 mRNA in any histological subtype of liposarcoma. Recurrent tumors did not
      show any difference in CDO1 expression when compared to primary tumors. CDO1
      expression was upregulated as human mesenchymal stem cells (hMSCs) undergo
      differentiation into mature adipocytes. Our results suggest that CDO1 is a marker
      of liposarcoma progression and adipogenic differentiation. 

PMID- 24741339
TI  - Efficacy of Tenofovir 1% Vaginal Gel in Reducing the Risk of HIV-1 and HSV-2
      Infection.
AB  - Human Immunodeficiency Virus (HIV) is a retrovirus that can result in rare
      opportunistic infections occurring in humans. The onset of these infections is
      known as Acquired Immune Deficiency Syndrome (AIDS). Sexual transmission is
      responsible for the majority of infections 1, resulting in transmission of HIV
      due to infected semen or vaginal and cervical secretions containing infected
      lymphocytes. HIV microbicides are formulations of chemical or biological agents
      that can be applied to the vagina or rectum with the intention of reducing the
      acquisition of HIV. Tenofovir is an NRTI that is phosphorylated by adenylate
      kinase to tenofovir diphosphate, which in turn competes with deoxyadeosine 5'
      triphosphate for incorporation into newly synthesized HIV DNA. Once incorporated,
      tenofovir diphosphate results in chain termination, thus inhibiting viral
      replication. Tenofovir has been formulated into a range of vaginal formulations,
      such as rings, tablets gels and films. It has been shown to safe and effective in
      numerous animal models, while demonstrating safety and acceptability in numerous
      human trials. The most encouraging results came from the CAPRISA 004 clinical
      trial which demonstrated that a 1% Tenofovir vaginal gel reduced HIV infection by
      approximately 39%. 

PMID- 24741340
TI  - Novel synthesis of cellulose-based diblock copolymer of poly(hydroxyethyl
      methacrylate) by mechanochemical reaction.
AB  - The mechanical fracture of polymer produces polymeric free radical chain-ends, by
      which liner block copolymers have been synthesized. A diblock copolymer of
      microcrystalline cellulose (MCC) and poly 2-hydroxyethyl methacrylate (pHEMA) was
      produced by the mechanochemical polymerization under vacuum and room temperature.
      The fraction of pHEMA in MCC-block-pHEMA produced by the mechanochemical
      polymerization increased up to 21 mol% with increasing fracture time (~6 h).
      Then, the tacticities of HEMA sequences in MCC-block-pHEMA varied according to
      the reaction time. In the process of mechanochemical polymerization, cellulose
      could play the role of a radical polymerization initiator capable of controlling
      stereoregularity.

PMID- 24741341
TI  - Cooperative search and rescue with artificial fishes based on fish-swarm
      algorithm for underwater wireless sensor networks.
AB  - This paper presents a searching control approach for cooperating mobile sensor
      networks. We use a density function to represent the frequency of distress
      signals issued by victims. The mobile nodes' moving in mission space is similar
      to the behaviors of fish-swarm in water. So, we take the mobile node as
      artificial fish node and define its operations by a probabilistic model over a
      limited range. A fish-swarm based algorithm is designed requiring local
      information at each fish node and maximizing the joint detection probabilities of
      distress signals. Optimization of formation is also considered for the searching
      control approach and is optimized by fish-swarm algorithm. Simulation results
      include two schemes: preset route and random walks, and it is showed that the
      control scheme has adaptive and effective properties. 

PMID- 24741343
TI  - Effective control of bioelectricity generation from a microbial fuel cell by
      logical combinations of pH and temperature.
AB  - In this study, a microbial fuel cell (MFC) with switchable power release is
      designed, which can be logically controlled by combinations of the most
      physiologically important parameters such as "temperature" and "pH." Changes in
      voltage output in response to temperature and pH changes were significant in
      which voltage output decreased sharply when temperature was lowered from 30
      degrees C to 10 degrees C or pH was decreased from 7.0 to 5.0. The switchability
      of the MFC comes from the microbial anode whose activity is affected by the
      combined medium temperature and pH. Changes in temperature and pH cause
      reversible activation-inactivation of the bioanode, thus affecting the activity
      of the entire MFC. With temperature and pH as input signals, an AND logic
      operation is constructed for the MFC whose power density is controlled. The
      developed system has the potential to meet the requirement of power supplies
      producing electrical power on-demand for self-powered biosensors or biomedical
      devices. 

PMID- 24741344
TI  - Optimization of integrated impeller mixer via radiotracer experiments.
AB  - Radiotracer experiments are carried out in order to determine the mean residence
      time (MRT) as well as percentage of dead zone, V dead (%), in an integrated mixer
      consisting of Rushton and pitched blade turbine (PBT). Conventionally,
      optimization was performed by varying one parameter and others were held constant
      (OFAT) which lead to enormous number of experiments. Thus, in this study, a 4
      factor 3-level Taguchi L9 orthogonal array was introduced to obtain an accurate
      optimization of mixing efficiency with minimal number of experiments. This paper
      describes the optimal conditions of four process parameters, namely, impeller
      speed, impeller clearance, type of impeller, and sampling time, in obtaining MRT
      and V dead (%) using radiotracer experiments. The optimum conditions for the
      experiments were 100 rpm impeller speed, 50 mm impeller clearance, Type A mixer,
      and 900 s sampling time to reach optimization.

PMID- 24741342
TI  - IgG, IgM, and IgA antinuclear antibodies in discoid and systemic lupus
      erythematosus patients.
AB  - IgG antinuclear antibodies (ANAs) are elevated in patients with systemic lupus
      erythematosus (SLE) compared with patients with discoid lupus erythematosus
      (DLE). To provide an expanded immunologic view of circulating ANAs in lupus
      patients, we compared the expressions of IgG, IgM, and IgA ANAs in DLE and SLE
      patients. In this cross-sectional study, sera from age-, gender-, and ethnic
      matched SLE (N = 35), DLE (N = 23), and normal patients (N = 22) were tested for
      IgG, IgM, and IgA ANAs using enzyme-linked immunosorbent assays (ELISAs) and
      indirect immunofluorescence (IIF) with monkey esophagus as substrate. ELISAs
      showed elevated levels of IgG ANA, IgM ANA, and IgG/IgM ANA ratios in SLE
      patients compared with DLE and normal patients. IgA ANA expression was higher in
      SLE and DLE patients versus normal patients. IIF studies showed higher
      percentages of patients positive for IgG, IgM, and IgA ANAs in the SLE group.
      Higher IgG/IgM ANA ratios in SLE than DLE show enhanced class-switching and a
      more sustained humoral response in SLE. They also suggest a potential connection
      of IgM ANAs with disease containment. 

PMID- 24741345
TI  - An inequality of meromorphic functions and its application.
AB  - By applying Ahlfors theory of covering surface, we establish a fundamental
      inequality of meromorphic function dealing with multiple values in an angular
      domain. As an application, we prove the existence of some new singular directions
      for a meromorphic function f, namely a Bloch direction and a pseudo-T direction
      for f. 

PMID- 24741346
TI  - Laboratory study of the displacement coalbed CH4 process and efficiency of CO2
      and N2 injection.
AB  - ECBM displacement experiments are a direct way to observe the gas displacement
      process and efficiency by inspecting the produced gas composition and flow rate.
      We conducted two sets of ECBM experiments by injecting N2 and CO2 through four
      large parallel specimens (300 * 50 * 50 mm coal briquette). N2 or CO2 is injected
      at pressures of 1.5, 1.8, and 2.2 MPa and various crustal stresses. The changes
      in pressure along the briquette and the concentration of the gas mixture flowing
      out of the briquette were analyzed. Gas injection significantly enhances CBM
      recovery. Experimental recoveries of the original extant gas are in excess of 90%
      for all cases. The results show that the N2 breakthrough occurs earlier than the
      CO2 breakthrough. The breakthrough time of N2 is approximately 0.5 displaced
      volumes. Carbon dioxide, however, breaks through at approximately 2 displaced
      volumes. Coal can adsorb CO2, which results in a slower breakthrough time. In
      addition, ground stress significantly influences the displacement effect of the
      gas injection.

PMID- 24741347
TI  - Motion adaptive vertical handoff in cellular/WLAN heterogeneous wireless network.
AB  - In heterogeneous wireless network, vertical handoff plays an important role for
      guaranteeing quality of service and overall performance of network. Conventional
      vertical handoff trigger schemes are mostly developed from horizontal handoff in
      homogeneous cellular network. Basically, they can be summarized as hysteresis
      based and dwelling-timer-based algorithms, which are reliable on avoiding
      unnecessary handoff caused by the terminals dwelling at the edge of WLAN
      coverage. However, the coverage of WLAN is much smaller compared with cellular
      network, while the motion types of terminals can be various in a typical outdoor
      scenario. As a result, traditional algorithms are less effective in avoiding
      unnecessary handoff triggered by vehicle-borne terminals with various speeds.
      Besides that, hysteresis and dwelling-timer thresholds usually need to be
      modified to satisfy different channel environments. For solving this problem, a
      vertical handoff algorithm based on Q-learning is proposed in this paper. Q
      learning can provide the decider with self-adaptive ability for handling the
      terminals' handoff requests with different motion types and channel conditions.
      Meanwhile, Neural Fuzzy Inference System (NFIS) is embedded to retain a
      continuous perception of the state space. Simulation results verify that the
      proposed algorithm can achieve lower unnecessary handoff probability compared
      with the other two conventional algorithms. 

PMID- 24741348
TI  - Research on the food security condition and food supply capacity of Egypt.
AB  - Food security is chronically guaranteed in Egypt because of the food subsidy
      policy of the country. However, the increasing Egyptian population is straining
      the food supply. To study changes in Egyptian food security and future food
      supply capacity, we analysed the historical grain production, yield per unit,
      grain-cultivated area, and per capita grain possession of Egypt. The GM (1,1)
      model of the grey system was used to predict the future population. Thereafter,
      the result was combined with scenario analysis to forecast the grain possession
      and population carrying capacity of Egypt under different scenarios. Results show
      that the increasing population and limitations in cultivated land will strain
      Egyptian food security. Only in high cultivated areas and high grain yield
      scenarios before 2020, or in high cultivated areas and mid grain yield scenarios
      before 2015, can food supply be basically satisfied (assurance rate >= 80%) under
      a standard of 400 kg per capita. Population carrying capacity in 2030 is between
      51.45 and 89.35 million. Thus, we propose the use of advanced technologies in
      agriculture and the adjustment of plant structure and cropping systems to improve
      land utilization efficiency. Furthermore, urbanization and other uses of
      cultivated land should be strictly controlled to ensure the planting of grains.

PMID- 24741349
TI  - Ammonia volatilization losses from paddy fields under controlled irrigation with
      different drainage treatments.
AB  - The effect of controlled drainage (CD) on ammonia volatilization (AV) losses from
      paddy fields under controlled irrigation (CI) was investigated by managing water
      table control levels using a lysimeter. Three drainage treatments were
      implemented, namely, controlled water table depth 1 (CWT1), controlled water
      table depth 2 (CWT2), and controlled water table depth 3 (CWT3). As the water
      table control levels increased, irrigation water volumes in the CI paddy fields
      decreased. AV losses from paddy fields reduced due to the increases in water
      table control levels. Seasonal AV losses from CWT1, CWT2, and CWT3 were 59.8,
      56.7, and 53.0 kg N ha(-1), respectively. AV losses from CWT3 were 13.1% and 8.4%
      lower than those from CWT1 and CWT2, respectively. A significant difference in
      the seasonal AV losses was confirmed between CWT1 and CWT3. Less weekly AV losses
      followed by TF and PF were also observed as the water table control levels
      increased. The application of CD by increasing water table control levels to a
      suitable level could effectively reduce irrigation water volumes and AV losses
      from CI paddy fields. The combination of CI and CD may be a feasible water
      management method of reducing AV losses from paddy fields.

PMID- 24741350
TI  - Unconventional bearing capacity analysis and optimization of multicell box
      girders.
AB  - This study deals with unconventional bearing capacity analysis and the procedure
      of optimizing a two-cell box girder. The generalized model which enables the
      local stress-strain analysis of multicell girders was developed based on the
      principle of cross-sectional decomposition. The applied methodology is verified
      using the experimental data (Djelosevic et al., 2012) for traditionally formed
      box girders. The qualitative and quantitative evaluation of results obtained for
      the two-cell box girder is realized based on comparative analysis using the
      finite element method (FEM) and the ANSYS v12 software. The deflection function
      obtained by analytical and numerical methods was found consistent provided that
      the maximum deviation does not exceed 4%. Multicell box girders are rationally
      designed support structures characterized by much lower susceptibility of their
      cross-sectional elements to buckling and higher specific capacity than
      traditionally formed box girders. The developed local stress model is applied for
      optimizing the cross section of a two-cell box carrier. The author points to the
      advantages of implementing the model of local stresses in the optimization
      process and concludes that the technological reserve of bearing capacity amounts
      to 20% at the same girder weight and constant load conditions. 

PMID- 24741351
TI  - On the higher power sums of reciprocal higher-order sequences.
AB  - Let {u(n)} be a higher-order linear recursive sequence. In this paper, we use the
      properties of error estimation and the analytic method to study the reciprocal
      sums of higher power of higher-order sequences. Then we establish several new and
      interesting identities relating to the infinite and finite sums.

PMID- 24741352
TI  - An iterative approach for the optimization of pavement maintenance management at
      the network level.
AB  - Pavement maintenance is one of the major issues of public agencies. Insufficient
      investment or inefficient maintenance strategies lead to high economic expenses
      in the long term. Under budgetary restrictions, the optimal allocation of
      resources becomes a crucial aspect. Two traditional approaches (sequential and
      holistic) and four classes of optimization methods (selection based on ranking,
      mathematical optimization, near optimization, and other methods) have been
      applied to solve this problem. They vary in the number of alternatives considered
      and how the selection process is performed. Therefore, a previous understanding
      of the problem is mandatory to identify the most suitable approach and method for
      a particular network. This study aims to assist highway agencies, researchers,
      and practitioners on when and how to apply available methods based on a
      comparative analysis of the current state of the practice. Holistic approach
      tackles the problem considering the overall network condition, while the
      sequential approach is easier to implement and understand, but may lead to
      solutions far from optimal. Scenarios defining the suitability of these
      approaches are defined. Finally, an iterative approach gathering the advantages
      of traditional approaches is proposed and applied in a case study. The proposed
      approach considers the overall network condition in a simpler and more intuitive
      manner than the holistic approach. 

PMID- 24741353
TI  - An Osgood type regularity criterion for the 3D Boussinesq equations.
AB  - We consider the three-dimensional Boussinesq equations, and obtain an Osgood type
      regularity criterion in terms of the velocity gradient. 

PMID- 24741354
TI  - Overexpression of DcR3 and its significance on tumor cell differentiation and
      proliferation in glioma.
AB  - BACKGROUND: Overexpression of decoy receptor 3 (DcR3) have been reported in
      various classes of malignancies. However, its expression and clinicopathological
      contribution in gliomas has not been fully elucidated. OBJECTIVE: To explore the
      expression and clinical significance of DcR3 protein in relation to tumor cell
      differentiation and proliferation in glioma cell lines and tissues. METHODS: One
      hundred and twenty-five samples of glioma patients and 18 cases of normal brain
      tissues were recruited. The expression of DcR3 protein was detected using
      immunohistochemistry. Tumor differentiation was assessed by histologic characters
      and the status of glial fibrillary acidic protein (GFAP). Tumor cell labeling
      indexes (LIs) of Ki-67 and PCNA were also obtained. The relationship between the
      DcR3 level and clinicopathological features was investigated, including tumor
      differentiation, LIs, and survival. Meanwhile, the expression of DcR3 protein was
      also measured in the supernatants of 8 glioma cell lines and glioma cells freshly
      prepared from 8 human glioblastoma specimens by using western blot. RESULTS: The
      level of DcR3 protein in gliomas was significantly higher than that in normal
      brain tissues (P < 0.01). DcR3 expression showed positive correlations with tumor
      pathological grade (r = 0.621, P < 0.01) and negative with GFAP expression (r = 
      0.489, P < 0.01). Furthermore, there were positive correlations between DcR3
      expression and Ki-67, PCNA LIs (r = 0.529, P < 0.01; r = 0.556, P < 0.01). The
      survival in the DcR3 negative group was 50 +/- 1.79 months, longer than that of
      the DcR3 positive group (48.36 +/- 2.90), however, without significance (P =
      0.149). Different levels of DcR3 could also be detected in the culturing
      supernatants of all the 8 glioma cell lines and glioma cells freshly obtained
      from 8 human glioblastoma specimens. CONCLUSIONS: The overexpression of DcR3
      might play a crucial role in the tumorigenesis, differentiation, and
      proliferation of glioma.

PMID- 24741355
TI  - Prevalence of Sarcoptes scabiei infection in pet dogs in southern China.
AB  - Little is known about the prevalence of Sarcoptes scabiei infection in pet dogs
      in China. In the present study, the prevalence of S. scabiei infection in pet
      dogs in Guangzhou, southern China, was investigated between January and December,
      2009. A total of 3,977 pet dogs admitted to animal hospitals were examined for
      the presence of S. scabiei using a parasitological approach. The average
      prevalence of S. scabiei infection in pet dogs is 1.18% (95% confidence interval
      (CI): 0.85-1.52%). The prevalence of S. scabiei was higher in winter (1.42%; 95%
      CI: 0.29-2.55%), summer (1.39%; 95% CI: 0.83-1.96%), and autumn (1.1%; 95% CI:
      0.53-1.68%) than in spring (0.63%; 95% CI: 0.02-1.25%). Furthermore, the
      prevalence of S. scabiei was the highest in Pekingese (21.88%; 95% CI: 7.55
      36.2%), followed by Papillon (5.26%; 95% CI: 0-11.06%) and Bichon Frise (3.19%;
      95% CI: 0-6.75%). The results of the present investigation indicate that S.
      scabiei infection is prevalent in pet dogs in Guangzhou, China, which provides
      relevant "baseline" data for conducting control strategies and measures against
      scabies in this region and elsewhere in China. To our knowledge, this is the
      first comprehensive report of S. scabiei prevalence in pet dogs in China. 

PMID- 24741356
TI  - Land use changes and their effects on the value of ecosystem services in the
      small Sanjiang plain in China.
AB  - The small Sanjiang plain is one of the most important commodity grain production
      bases and the largest fresh water wetland in China. Due to the rapid expansion of
      agricultural activities in the past 30 years, the contradiction between economic
      development and the loss of ecosystem services has become an issue of increasing
      concern in the area. In this study, we analysed land use changes and the loss of
      ecosystem services value caused by these changes. We found that cropland sprawl
      was predominant and occurred in forest, wetland, and grassland areas in the small
      Sanjiang plain from 1980 to 2010. Using a model to evaluate ecosystem services
      value, we calculated that the decreased values of ecosystem services were 169.88
      * 10(8) Yuan from 1980 to 2000 and 120.00 * 10(8) Yuan from 2000 to 2010. All of
      the ecosystem services were diminished from 1980 to 2010 except for food
      production. Therefore, the loss of ecosystem services value should be considered
      by the policymakers of land use and development. 

PMID- 24741357
TI  - The effect of water stress on some morphological, physiological, and biochemical
      characteristics and bud success on apple and quince rootstocks.
AB  - The effects of different water stress (control, medium, and severe) on some
      morphological, physiological, and biochemical characteristics and bud success of
      M9 apple and MA quince rootstocks were determined. The results showed that water
      stress significantly affected most morphological, physiological, and biochemical
      characteristics as well as budding success on the both rootstocks. The increasing
      water stress decreased the relative shoot length, diameter, and plant total fresh
      and dry weights. Leaf relative water content and chlorophyll index decreased
      while electrolyte leakage increased with the increase of water stress in both
      rootstocks. An increase in water stress also resulted in reduction in budding
      success in Vista Bella/M9 (79.33% and 46.67%) and Santa Maria/MA (70.33% and
      15.33%) combinations. However, the water stress in Santa Maria/MA was more
      prominent. The increase in water stress resulted in higher peroxidase activities
      as well as phenol contents in both rootstocks. Although catalase activity,
      anthocyanin, and proline contents increased with the impact of stress, this was
      not statistically significant. The results suggest that the impact of stress
      increased with the increase of water stress; therefore, growers should be careful
      when using M9 and MA rootstocks in both nursery and orchards where water scarcity
      is present. 

PMID- 24741358
TI  - Analysis of volatile components of cape gooseberry (Physalis peruviana L.) grown
      in Turkey by HS-SPME and GC-MS.
AB  - Volatile components in cape gooseberry fruit at ripe stage were collected using
      headspace-solid phase microextraction, and analyzed by gas chromatography-mass
      spectrometry. Three solid phase microextraction fiber coatings (DVB/CAR/PDMS,
      CAR/PDMS, and PDMS/DVB) were tested for evaluation of volatile compounds.
      DVB/CAR/PDMS fiber showed a strong extraction capacity for volatile compounds and
      produced the best result in case of total peak areas. A total of 133 volatile
      compounds were identified in fruit pulp; among them 1-hexanol (6.86%), eucalyptol
      (6.66%), ethyl butanoate (6.47%), ethyl octanoate (4.01%), ethyl decanoate
      (3.39%), 4-terpineol (3.27%), and 2-methyl-1-butanol (3.10%) were the major
      components in the sample extracts. 

PMID- 24741359
TI  - A novel complex networks clustering algorithm based on the core influence of
      nodes.
AB  - In complex networks, cluster structure, identified by the heterogeneity of nodes,
      has become a common and important topological property. Network clustering
      methods are thus significant for the study of complex networks. Currently, many
      typical clustering algorithms have some weakness like inaccuracy and slow
      convergence. In this paper, we propose a clustering algorithm by calculating the
      core influence of nodes. The clustering process is a simulation of the process of
      cluster formation in sociology. The algorithm detects the nodes with core
      influence through their betweenness centrality, and builds the cluster's core
      structure by discriminant functions. Next, the algorithm gets the final cluster
      structure after clustering the rest of the nodes in the network by optimizing
      method. Experiments on different datasets show that the clustering accuracy of
      this algorithm is superior to the classical clustering algorithm (Fast-Newman
      algorithm). It clusters faster and plays a positive role in revealing the real
      cluster structure of complex networks precisely. 

PMID- 24741360
TI  - Energy-efficient routing control algorithm in large-scale WSN for water
      environment monitoring with application to Three Gorges Reservoir area.
AB  - The typical application backgrounds of large-scale WSN (wireless sensor networks)
      for the water environment monitoring in the Three Gorges Reservoir are large
      coverage area and wide distribution. To maximally prolong lifetime of large-scale
      WSN, a new energy-saving routing algorithm has been proposed, using the method of
      maximum energy-welfare optimization clustering. Firstly, temporary clusters are
      formed based on two main parameters, the remaining energy of nodes and the
      distance between a node and the base station. Secondly, the algorithm adjusts
      cluster heads and optimizes the clustering according to the maximum energy
      welfare of the cluster by the cluster head shifting mechanism. Finally, in order
      to save node energy efficiently, cluster heads transmit data to the base station
      in single-hop and multihop way. Theoretical analysis and simulation results show
      that the proposed algorithm is feasible and advanced. It can efficiently save the
      node energy, balance the energy dissipation of all nodes, and prolong the network
      lifetime. 

PMID- 24741361
TI  - How fast is recovery of impaired glucose tolerance after 21-day bed rest (NUC
      study) in healthy adults?
AB  - AIM: We hypothesized that 4 days of normal daily activity after 21 days of
      experimental bed rest (BR) will not reverse BR induced impaired glucose
      tolerance. DESIGN: Glucose tolerance of seven male, healthy, untrained test
      subjects (age: 27.6 (3.3) years (mean (SD)); body mass: 78.6 (6.4) kg; height:
      1.81 (0.04)  m; VO2 max: 39.5 (5.4) ml/kg body mass/min) was studied. They stayed
      twice in the metabolic ward (crossover design), 21 days in bed and 7 days before
      and after BR each. Oral glucose tolerance tests were applied before, on day 21 of
      BR, and 5 and 14 days after BR. RESULTS: On day 21 of BR, AUC(120 min) of glucose
      concentration was increased by 28.8 (5.2)% and AUC(120 min) of insulin by 35.9
      (10.2)% (glucose: P < 0.001; insulin: P = 0.02). Fourteen days after BR, AUC(120
      min) of serum insulin concentrations returned to pre-bed-rest concentrations (P =
      0.352) and AUC(120 min) of glucose was still higher (P = 0.038). Insulin
      resistance did not change, but sensitivity index was reduced during BR (P =
      0.005). CONCLUSION: Four days of light physical workload does not compensate
      inactivity induced impaired glucose tolerance. An individually tailored and
      intensified training regime is mandatory in patients being in bed rest to get
      back to normal glucose metabolism in a reasonable time frame.

PMID- 24741363
TI  - Modeling and performance analysis of an improved movement-based location
      management scheme for packet-switched mobile communication systems.
AB  - One of the key technologies to support mobility of mobile station (MS) in mobile
      communication systems is location management which consists of location update
      and paging. In this paper, an improved movement-based location management scheme
      with two movement thresholds is proposed, considering bursty data traffic
      characteristics of packet-switched (PS) services. The analytical modeling for
      location update and paging signaling loads of the proposed scheme is developed
      thoroughly and the performance of the proposed scheme is compared with that of
      the conventional scheme. We show that the proposed scheme outperforms the
      conventional scheme in terms of total signaling load with an appropriate
      selection of movement thresholds. 

PMID- 24741362
TI  - Knockdown of zebrafish blood vessel epicardial substance results in incomplete
      retinal lamination.
AB  - Cell polarity during eye development determines the normal retinal lamination and
      differentiation of photoreceptor cells in the retina. In vertebrates, blood
      vessel epicardial substance (Bves) is known to play an important role in the
      formation and maintenance of the tight junctions essential for epithelial cell
      polarity. In the current study, we generated a transgenic zebrafish Bves (zbves)
      promoter-EGFP zebrafish line to investigate the expression pattern of Bves in the
      retina and to study the role of zbves in retinal lamination. Immunostaining with
      different specific antibodies from retinal cells and transmission electron
      microscopy were used to identify the morphological defects in normal and Bves
      knockdown zebrafish. In normal zebrafish, Bves is located at the apical junctions
      of embryonic retinal neuroepithelia during retinogenesis; later, it is strongly
      expressed around inner plexiform layer (IPL) and retinal pigment epithelium
      (RPE). In contrast, a loss of normal retinal lamination and cellular polarity was
      found with undifferentiated photoreceptor cells in Bves knockdown zebrafish.
      Herein, our results indicated that disruption of Bves will result in a loss of
      normal retinal lamination. 

PMID- 24741364
TI  - Rice photosynthetic productivity and PSII photochemistry under nonflooded
      irrigation.
AB  - Nonflooded irrigation is an important water-saving rice cultivation technology,
      but little is known on its photosynthetic mechanism. The aims of this work were
      to investigate photosynthetic characteristics of rice during grain filling stage
      under three nonflooded irrigation treatments: furrow irrigation with plastic
      mulching (FIM), furrow irrigation with nonmulching (FIN), and drip irrigation
      with plastic mulching (DI). Compared with the conventional flooding (CF)
      treatment, those grown in the nonflooded irrigation treatments showed lower net
      photosynthetic rate (PN), lower maximum quantum yield (Fv/Fm), and lower
      effective quantum yield of PSII photochemistry (PhiPSII). And the poor
      photosynthetic characteristics in the nonflooded irrigation treatments were
      mainly attributed to the low total nitrogen content (TNC). Under non-flooded
      irrigation, the PN, Fv/Fm, and PhiPSII significantly decreased with a reduction
      in the soil water potential, but these parameters were rapidly recovered in the
      DI and FIM treatments when supplementary irrigation was applied. Moreover, The DI
      treatment always had higher photosynthetic productivity than the FIM and FIN
      treatments. Grain yield, matter translocation, and dry matter post-anthesis
      (DMPA) were the highest in the CF treatment, followed by the DI, FIM, and FIN
      treatments in turn. In conclusion, increasing nitrogen content in leaf of rice
      plants could be a key factor to improve photosynthetic capacity in nonflooded
      irrigation.

PMID- 24741365
TI  - Chain hexagonal cacti with the extremal eccentric distance sum.
AB  - Eccentric distance sum (EDS), which can predict biological and physical
      properties, is a topological index based on the eccentricity of a graph. In this
      paper we characterize the chain hexagonal cactus with the minimal and the maximal
      eccentric distance sum among all chain hexagonal cacti of length n, respectively.
      Moreover, we present exact formulas for EDS of two types of hexagonal cacti. 

PMID- 24741366
TI  - Health care expenditure and GDP in African countries: evidence from
      semiparametric estimation with panel data.
AB  - A large body of literature studies on the relationship between health care
      expenditure (HCE) and GDP have been analyzed using data intensively from
      developed countries, but little is known for other regions. This paper considers
      a semiparametric panel data analysis for the study of the relationship between
      per capita HCE and per capita GDP for 42 African countries over the period 1995
      2009. We found that infant mortality rate per 1,000 live births has a negative
      effect on per capita HCE, while the proportion of the population aged 65 is
      statistically insignificant in African countries. Furthermore, we found that the
      income elasticity is not constant but varies with income level, and health care
      is a necessity rather than a luxury for African countries. 

PMID- 24741367
TI  - Detection of impaired cognitive function in rat with hepatosteatosis model and
      improving effect of GLP-1 analogs (exenatide) on cognitive function in
      hepatosteatosis.
AB  - The aims of the study were to evaluate (1) detection of cognitive function
      changing in rat with hepatosteatosis model and (2) evaluate the effect of GLP-1
      analog (exenatide) on cognitive function in hepatosteatosis. In the study group,
      30% fructose was given in nutrition water to perform hepatosteatosis for 8 weeks
      to 18 male rats. Six male rats were chosen as control group and had normal
      nutrition. Fructose nutrition group were stratified into 3 groups. In first group
      (n = 6), intracerebroventricular (ICV) infusion of exenatide (n = 6) was given.
      ICV infusion of NaCl (n = 6) was given to second group. And also, the third group
      had no treatment. And also, rats were evaluated for passive avoidance learning
      (PAL) and liver histopathology. Mean levels of latency time were statistically
      significantly decreased in rats with hepatosteatosis than those of normal rats (P
      < 0.00001). However, mean level of latency time in rats with hepatosteatosis
      treated with ICV exenatide was statistically significantly increased than that of
      rats treated with ICV NaCl (P < 0.001). Memory performance falls off in rats with
      hepatosteatosis feeding on fructose (decreased latency time). However, GLP-1
      ameliorates cognitive functions (increased latency time) in rats with
      hepatosteatosis and releated metabolic syndrome. 

PMID- 24741368
TI  - Preoperative butyrylcholinesterase level as an independent predictor of overall
      survival in clear cell renal cell carcinoma patients treated with nephrectomy.
AB  - The prognostic factors for the overall survival (OS) of clear cell renal cell
      carcinoma (ccRCC) patients treated with nephrectomy are not well defined. In the
      present study, we investigated the prognostic significance of preoperative
      butyrylcholinesterase (BChE) levels in 400 ccRCC patients undergoing radical or
      partial nephrectomy from 1992 to 2013 at our institution. Univariate and
      multivariate analyses were performed to determine the clinical factors associated
      with OS. Among the enrolled patients, 302 were diagnosed with organ-confined
      disease only (T1-2N0M0), 16 with lymph node metastases, and 56 with distant
      metastases. The median preoperative BChE level was 250 U/L (normal range, 168-470
      U/L), and median follow-up period was 36 months. The 3-year OS rate in patients
      with preoperative BChE levels of >=100 U/L was significantly higher than in those
      with levels of <100 U/L (89.3% versus 77.7%, P = 0.004). On univariate analysis,
      performance status; anemia; hypoalbuminemia; preoperative levels of BChE,
      corrected calcium, and C-reactive protein; and distant metastasis status were
      significantly associated with OS. Multivariate analysis revealed that
      preoperative BChE levels and distant metastasis status were significantly
      associated with OS. Our findings suggest a possible role of preoperative BChE
      levels as an independent predictor of OS after nephrectomy in ccRCC patients. 

PMID- 24741369
TI  - Actual incidence and clinical behaviour of follicular thyroid carcinoma: an
      institutional experience.
AB  - Follicular thyroid carcinoma classically accounts for 10-32% of thyroid
      malignancies. We determined the incidence and the behaviour of follicular thyroid
      carcinoma in an endemic goitre area. A comparative analysis between minimally
      invasive and widely invasive follicular thyroid carcinoma was performed. The
      medical records of all patients who underwent thyroidectomy from October 1998 to
      April 2012 for thyroid malignancies were reviewed. Those who had a histological
      diagnosis of follicular carcinoma were included. Among 5203 patients, 130 (2.5%)
      were included. Distant metastases at presentation were observed in four patients.
      Sixty-six patients had a minimally invasive follicular carcinoma and 64 a widely
      invasive follicular carcinoma. In 63 patients an oxyphilic variant was
      registered. Minimally/widely invasive ratio was 41/26 for usual follicular
      carcinoma and 25/38 for oxyphilic variant (P < 0.05). Patients with widely
      invasive tumors had larger tumors (P < 0.001) and more frequently oxyphilic
      variant (P < 0.05) than those with minimally invasive tumours. No significant
      difference was found between widely invasive and minimally invasive tumors and
      between usual follicular carcinoma and oxyphilic variant regarding the recurrence
      rate (P = NS). The incidence of follicular thyroid carcinoma is much lower than
      classically retained. Aggressive treatment, including total thyroidectomy and
      radioiodine ablation, should be proposed to all patients. 

PMID- 24741370
TI  - Green channel guiding denoising on bayer image.
AB  - Denoising is an indispensable function for digital cameras. In respect that noise
      is diffused during the demosaicking, the denoising ought to work directly on
      bayer data. The difficulty of denoising on bayer image is the interlaced mosaic
      pattern of red, green, and blue. Guided filter is a novel time efficient explicit
      filter kernel which can incorporate additional information from the guidance
      image, but it is still not applied for bayer image. In this work, we observe that
      the green channel of bayer mode is higher in both sampling rate and Signal-to
      Noise Ratio (SNR) than the red and blue ones. Therefore the green channel can be
      used to guide denoising. This kind of guidance integrates the different color
      channels together. Experiments on both actual and simulated bayer images indicate
      that green channel acts well as the guidance signal, and the proposed method is
      competitive with other popular filter kernel denoising methods. 

PMID- 24741371
TI  - Dimensionality Reduction in Controlling Articulated Snake Robot for Endoscopy
      Under Dynamic Active Constraints.
AB  - This paper presents a real-time control framework for a snake robot with hyper
      kinematic redundancy under dynamic active constraints for minimally invasive
      surgery. A proximity query (PQ) formulation is proposed to compute the deviation
      of the robot motion from predefined anatomical constraints. The proposed method
      is generic and can be applied to any snake robot represented as a set of control
      vertices. The proposed PQ formulation is implemented on a graphic processing
      unit, allowing for fast updates over 1 kHz. We also demonstrate that the robot
      joint space can be characterized into lower dimensional space for smooth
      articulation. A novel motion parameterization scheme in polar coordinates is
      proposed to describe the transition of motion, thus allowing for direct manual
      control of the robot using standard interface devices with limited degrees of
      freedom. Under the proposed framework, the correct alignment between the visual
      and motor axes is ensured, and haptic guidance is provided to prevent excessive
      force applied to the tissue by the robot body. A resistance force is further
      incorporated to enhance smooth pursuit movement matched to the dynamic response
      and actuation limit of the robot. To demonstrate the practical value of the
      proposed platform with enhanced ergonomic control, detailed quantitative
      performance evaluation was conducted on a group of subjects performing simulated
      intraluminal and intracavity endoscopic tasks.

PMID- 24741373
TI  - Synthesis and Suzuki-Miyaura Cross-Coupling of Enantioenriched Secondary
      Potassium beta-Trifluoroboratoamides: Catalytic, Asymmetric Conjugate Addition of
      Bisboronic Acid and Tetrakis(dimethylamino)diboron to alpha,beta-Unsaturated
      Carbonyl Compounds.
AB  - Enantioenriched potassium beta-trifluoroboratoamides have been synthesized via an
      asymmetric, copper-catalyzed 1,4-addition of tetrahydroxydiboron (BBA) and
      tetrakis(dimethylamino)diboron to alpha,beta-unsaturated amides. These dibora
      reagents provide access to the desired organotrifluoroborates using effective and
      atom economical sources of boron. The copper-catalyzed beta-boration is extended
      to alpha,beta-unsaturated ketones and esters. Desired potassium
      organotrifluoroborates are synthesized with yields up to 92% and enantiomeric
      ratios up to 98:2. The enantioenriched potassium beta-trifluoroboratoamides are
      successfully cross-coupled with an array of aryl and heteroaryl chlorides in high
      yield with complete stereochemical fidelity as the transmetalation proceeds
      through an SE2 mechanism via an open transition state.

PMID- 24741372
TI  - CD8+ T Cell Responses to Plasmodium and Intracellular Parasites.
AB  - Parasitic protozoa are major threats to human health affecting millions of people
      around the world. Control of these infections by the host immune system relies on
      a myriad of immunological mechanisms that includes both humoral and cellular
      immunity. CD8+ T cells contribute to the control of these parasitic infections in
      both animals and humans. Here, we will focus on the CD8+ T cell response against
      a subset of these protozoa: Plasmodium, Toxoplasma gondii, Leishmania and
      Trypanosoma cruzi, with an emphasis on experimental rodent systems. It is evident
      a complex interaction occurs between CD8+ T cells and the invading protozoa. A
      detailed understanding of how CD8+ T cells mediate protection should provide the
      basis for the development of effective vaccines that prevent and control
      infections by these parasites.

PMID- 24741374
TI  - Capsule endoscopy in the small bowel Crohn's disease.
AB  - CD is a chronic inflammatory disorder associated to mucosal and transmural
      inflammation of the bowel wall. It is well known that CD can affect the entire
      gastrointestinal. Therefore, ileocolonoscopy and biopsies of the terminal ileum
      as well as of each colonic segment to look for microscopic evidence of CD are the
      first-line procedures to establish the diagnosis. However, it has been observed
      that up to 30% of the patients have only small bowel involvement. Evaluation of
      the small bowel has been made with radiological procedures, barium radiography,
      and abdominal computed tomography or by ileocolonoscopy or enteroscopy, but they
      have many recognized limitations. CE is undoubtedly a very useful diagnostic tool
      proposed to observe small-bowel lesions undetectable by conventional endoscopy or
      radiologic studies. We review different studies that have been published
      reporting the use of CE in suspected and evaluation of the extension or the
      recurrence in CD and also its use in pediatric population and its complications. 

PMID- 24741375
TI  - Enzyme-triggered PEGylated siRNA-nanoparticles for controlled release of siRNA.
AB  - A key goal of our recent research efforts has been to develop novel 'triggerable
      nanoparticle' systems with real potential utility in vivo. These are designed to
      be stable from the point of administration until a target site of interest is
      reached, then triggered for the controlled release of therapeutic agent
      payload(s) at the target site by changes in local endogenous conditions or
      through the application of some exogenous stimulus. Here we describe
      investigations into the use of enzymes to trigger RNAi-mediated therapy through a
      process of enzyme-assisted nanoparticle triggerability. Our approach is to use
      PEG(2000)-peptidyl lipids with peptidyl moieties sensitive to tumour-localized
      elastase or matrix metalloproteinase-2 digestion, and from these prepare putative
      enzyme-triggered PEGylated siRNA-nanoparticles. Our results provide initial proof
      of concept in vitro. From these data, we propose that this concept should be
      applicable for functional delivery of therapeutic nucleic acids to tumour cells
      in vivo, although the mechanism for enzyme-assisted nanoparticle triggerability
      remains to be fully characterized. 

PMID- 24741376
TI  - Controllable edge feature sharpening for dental applications.
AB  - This paper presents a new approach to sharpen blurred edge features in scanned
      tooth preparation surfaces generated by structured-light scanners. It aims to
      efficiently enhance the edge features so that the embedded feature lines can be
      easily identified in dental CAD systems, and to avoid unnatural oversharpening
      geometry. We first separate the feature regions using graph-cut segmentation,
      which does not require a user-defined threshold. Then, we filter the face normal
      vectors to propagate the geometry from the smooth region to the feature region.
      In order to control the degree of the sharpness, we propose a feature distance
      measure which is based on normal tensor voting. Finally, the vertex positions are
      updated according to the modified face normal vectors. We have applied the
      approach to scanned tooth preparation models. The results show that the blurred
      edge features are enhanced without unnatural oversharpening geometry. 

PMID- 24741379
TI  - Fixation of acute distal biceps tendon ruptures using mitek anchors: a
      retrospective study.
AB  - PURPOSE OF THIS STUDY: The aim of this study was to evaluate the outcomes of
      surgical intra-osseous fixation of the distal tendon of the ruptured biceps
      brachii muscle using Mitek anchors. MATERIALS AND METHODS: Between 2005 and 2011,
      seven patients underwent unilateral distal biceps tendon repair using Mitek
      anchors. All patients were men aged between 36 and 47 years. Six patients were
      assessed by physical examination and use of the Disabilities of the Arm,
      Shoulder, and Hand (DASH) questionnaire. RESULTS: Surgery was performed within 3
      to 17 days of rupture with a mean follow-up of 35 months. Of the six fully
      completed DASH questionnaires, three patients had a score of 0, and three
      patients had scores of 5.8, 10 and 10.8, respectively (10.1 is the mean score for
      the general population). Transient paraesthesias in the lateral antebrachial
      cutaneous nerve region occurred in two patients and one patient experienced a
      transient stiffness of the elbow due to scarring of the wound. No major
      complicatons have occurred. CONCLUSION: The use of Mitek anchors for the re
      insertion of the ruptured distal biceps tendon proved to be a safe and effective
      technique with excellent functional results in our series.

PMID- 24741378
TI  - Down-regulation of the clotting cascade by the protein C pathway.
AB  - The protein C pathway provides important biological activities to maintain the
      fluidity of the circulation, prevent thrombosis, and protect the integrity of the
      vasculature in response to injury. Activated protein C (APC), in concert with its
      cofactors and cell receptors, assembles in specific macromolecular complexes to
      provide efficient proteolysis of multiple substrates that result in anticoagulant
      and cytoprotective activities. Numerous studies on APC's structure-function
      relation with its cofactors, cell receptors, and substrates provide valuable
      insights into the molecular mechanisms and presumed assembly of the
      macromolecular complexes that are responsible for APC's activities. These
      insights allow for molecular engineering approaches specifically targeting the
      interaction of APC with one of its substrates or cofactors. Thus far, these
      approaches resulted in several anticoagulant-selective and cytoprotective
      selective APC mutants, which provide unique insights into the relative
      contributions of APC's anticoagulant or cytoprotective activities to the
      beneficial effects of APC in various murine injury and disease models. Because of
      its multiple physiological and pharmacological activities, the anticoagulant and
      cytoprotective protein C pathway have important implications for the
      (patho)physiology of vascular disease and for translational research exploring
      novel therapeutic strategies to combat complex medical disorders such as
      thrombosis, inflammation, ischemic stroke and neurodegenerative disease.

PMID- 24741377
TI  - Perspectives on Non-Animal Alternatives for Assessing Sensitization Potential in
      Allergic Contact Dermatitis.
AB  - Skin sensitization remains a major environmental and occupational health hazard.
      Animal models have been used as the gold standard method of choice for estimating
      chemical sensitization potential. However, a growing international drive and
      consensus for minimizing animal usage have prompted the development of in vitro
      methods to assess chemical sensitivity. In this paper, we examine existing
      approaches including in silico models, cell and tissue based assays for
      distinguishing between sensitizers and irritants. The in silico approaches that
      have been discussed include Quantitative Structure Activity Relationships (QSAR)
      and QSAR based expert models that correlate chemical molecular structure with
      biological activity and mechanism based read-across models that incorporate
      compound electrophilicity. The cell and tissue based assays rely on an assortment
      of mono and co-culture cell systems in conjunction with 3D skin models. Given the
      complexity of allergen induced immune responses, and the limited ability of
      existing systems to capture the entire gamut of cellular and molecular events
      associated with these responses, we also introduce a microfabricated platform
      that can capture all the key steps involved in allergic contact sensitivity.
      Finally, we describe the development of an integrated testing strategy comprised
      of two or three tier systems for evaluating sensitization potential of chemicals.

PMID- 24741380
TI  - Acute Hematogenous Infection of Revision Total Hip Arthroplasty by Oral Bacteria
      in a Patient without a History of Dental Procedures: Case Report.
AB  - The risk of periprosthetic joint infection from hematogenous bacterial seeding is
      increased in patients undergoing dental procedures that facilitate the
      development of bacteremia. We herein report the case of a patient without a
      history of dental procedures who suffered from an acute metastatic infection of a
      hip prosthesis by the oral bacterium Streptococcus mutans 18 months after
      undergoing revision total hip arthroplasty. The patient was successfully treated
      by two-stage revision surgery. It is important to realize that the efficacy of
      antibiotic prophylaxis against joint infections has not yet been convincingly
      proven. As a result, optimal dental hygiene and regular dental visits may be more
      important than antibiotic prophylaxis for maintaining joint health. Therefore,
      orthopedic surgeons should educate patients with joint prostheses about good oral
      health. 

PMID- 24741381
TI  - Judgment in Older Adults with Normal Cognition, Cognitive Complaints, MCI, and
      Mild AD: Relation to Regional Frontal Gray Matter.
AB  - We investigated regional gray matter (GM) reduction as a predictor of judgment
      ability in 120 non-depressed older adults with varying degrees of cognitive
      complaints and/or impairment (including those with MCI and mild AD). Participants
      underwent neuropsychological assessment, including the Test of Practical Judgment
      (TOP-J), a recently developed instrument that evaluates judgment and problem
      solving related to safety, medical, social/ethical, and financial issues.
      Structural MR scanning included T1-weighted SPGR volumes acquired at 1.5 Tesla.
      We used voxel-based morphometry to analyze the relationship between GM density
      and TOP-J scores, controlling for age, education, gender, intracranial volume,
      verbal memory, and crystallized knowledge. Consistent with our hypothesis,
      judgment ability correlated with GM density in prefrontal regions (left inferior
      and superior frontal gyri). Findings extend previous observations of frontal
      involvement in higher-order cognitive abilities/executive functions and provide
      initial validation of the TOP-J's sensitivity to the integrity of these brain
      regions in individuals at risk for dementia.

PMID- 24741382
TI  - Debulking surgery for elephantiasis nostras with large ectatic podoplanin
      negative lymphatic vessels in patients with lipo-lymphedema.
AB  - OBJECTIVE: Elephantiasis nostras is a rare complication in advanced lipo
      lymphedema. While lipedema can be treated by liposuction and lymphedema by
      decongestive lymphatic therapy, elephantiasis nostras may need debulking surgery.
      METHODS: We present 2 cases of advanced lipo-lymphedema complicated by
      elephantiasis nostras. After tumescent microcannular laser-assisted liposuction
      both patients underwent a debulking surgery with a modification of Auchincloss
      Kim's technique. Histologic examination of the tissue specimen was performed.
      RESULTS: The surgical treatment was well tolerated and primary healing was
      uneventful. After primary wound healing and ambulation of the patients, a delayed
      ulceration with lymphorrhea developed. It was treated by surgical necrectomy and
      vacuum-assisted closure leading to complete healing. Mobility of the leg was much
      improved. Histologic examination revealed massive ectatic lymphatic vessels
      nonreactive for podoplanin. CONCLUSIONS: Debulking surgery can be an adjuvant
      technique for elephantiasis nostras in advanced lipo-lymphedema. Although delayed
      postoperative wound healing problems were observed, necrectomy and vacuum
      assisted closure achieved a complete healing. Histologic data suggest that the
      ectatic lymphatic vessels in these patients resemble finding in podoplanin
      knockout mice. The findings would explain the limitations of decongestive
      lymphatic therapy and tumescent liposuction in such patients and their
      predisposition to relapsing erysipelas.

PMID- 24741383
TI  - Split hemianterior tibialis turndown muscle flap for coverage of distal leg
      wounds with preservation of function.
AB  - OBJECTIVE: A hemisplit turndown tibialis anterior muscle flap is described for
      coverage of distal leg wounds with preservation of active extensor function for
      open wounds of the distal ankle is presented. This is a new flap not previously
      described and is another local option for coverage of selected distal leg wounds.
      METHODS: A description of the operative procedure and a clinical successful
      example is presented. RESULTS: The split hemitibialis anterior turndown muscle
      flap was successful and preserved function of the muscle and tendon. CONCLUSIONS:
      This is another option for coverage of difficult wounds of the lower extremity
      without sacrifice of function of the donor muscle.

PMID- 24741384
TI  - Treatment of dupuytren disease with injectable collagenase in a veteran
      population: a case series at the department of veterans affairs new jersey health
      care system.
AB  - INTRODUCTION: Clinical trials seeking to establish long-term efficacy of
      injectable collagenase clostridium histolyticum for treatment of Dupuytren
      disease are ongoing. In this quality improvement study, the efficacy, recurrence
      rate, and complications of collagenase injection for Dupuytren disease are
      reviewed in a population of Veteran patients. MATERIALS AND METHODS: A
      retrospective chart review was performed for patients who underwent treatment
      with injectable collagenase for Dupuytren disease from 2010 to 2013 at our
      regional Department of Veterans Affairs medical center. Data points of interest
      included the degree of joint contracture preoperatively, immediately after
      treatment, and at follow-up, complications, and patient satisfaction. RESULTS:
      Sixteen patients received 27 injections (18 metacarpophalangeal and 9 proximal
      interphalangeal injections). The mean time of follow-up was 12.3 months. There
      was a 50% or greater reduction of the original extension deficit in 74.1% (n =
      27) of the joints treated. Metacarpophalangeal joint recurrence was "high" (>=50
      degrees ) in 0% (n = 18) of joints, and "low" (5 degrees -50 degrees ) in 33.3%
      (n = 18) of joints with a mean follow-up of 12 months. Proximal interphalangeal
      joint recurrence was "high" (>=40 degrees ) in 18.5% (n = 9) of joints and "low"
      (5 degrees -40 degrees ) in 7.4% (n = 9) of joints with a mean follow-up of 12.9
      months. Minor complications were experienced in 93.8% (n = 16) of patients who
      underwent collagenase injection and included ecchymosis, skin laceration,
      injection-site swelling, injection-site hemorrhage, tenderness, and pruritus.
      Seventy-five percent (n = 12) of patients in our study reported they would
      undergo treatment with collagenase again. CONCLUSIONS: The case series presented
      demonstrates that injectable collagenase clostridium histolyticum produced a
      clinical success rate of 74.1% and is a safe method to treat Dupuytren disease.

PMID- 24741385
TI  - Genital Reconstruction After Weight Loss in Adipose Male Patients: A Case report.
AB  - OBJECTIVE: We introduce our surgical technique in two male genital reconstruction
      cases out of 15 post-bariatric patients. METHODS: At our Department for Plastic
      Surgery at the University Hospital Magdeburg, 15 patients, 6 male and 9 female,
      underwent a surgical abdominoplasty after weight loss in 2009. RESULTS: The
      average weight of the 15 patients was preoperatively 197.2 kg and the average
      hospital stay was of 14 days. In 2 cases, a second procedure for male genital
      reconstruction was necessary. After primary dietary measures and weight loss, we
      performed genital reconstruction in a second step with a sleeve-, Z-, VY-plasty
      and a "bilobed flap" to restore function and appearance of the male genitalia. In
      these patients, the average weight was 207.5 kg and hospital stay lasted 32 days.
      CONCLUSION: The increase of patients with obesity-related genital deformities
      will be expected in the future. Therefore, more controlled long-term studies
      should be published to develop guidelines for genital reconstruction techniques
      in plastic surgery.

PMID- 24741386
TI  - Biological effects of a disposable, canisterless negative pressure wound therapy
      system.
AB  - OBJECTIVE: Recent developments of negative pressure wound therapy (NPWT) systems
      have focused on making pumps smaller, lighter, and more portable. The recently
      introduced PICO system manages wound fluid through a highly breathable film
      within the dressing, thereby negating the need for a canister, which allows
      greater mobility and patient concordance. The aim of this study is to compare the
      biological effects of this system compared to a traditional NPWT system. METHODS:
      Laboratory tests were carried out to demonstrate the fluid handling properties of
      the PICOTM system. Porcine full thickness defect wounds and sutured incisional
      wounds were used to compare the biological effects. Wounds were treated with PICO
      dressings or traditional NPWT dressings and connected to either a PICO device or
      a traditional NPWT device. RESULTS: The PICO dressing manages exudate
      predominantly through evaporative loss (up to 85% of all fluid entering the
      dressing). Both traditional NPWT and the PICO system maintained therapeutic
      levels of negative pressure in all wounds. Both NPWT systems produced similar
      effects on wound edge contraction and microvascular blood flow in defect wounds.
      No significant changes in blood flow or wound contraction were noted in incision
      wounds for any NPWT combinations tested. CONCLUSIONS: The disposable,
      canisterless PICO NPWT system functions in the same manner as the traditional
      NPWT systems with regard to fluid handling, pressure transmission to the wound
      bed, tissue contraction, and changes in blood flow.

PMID- 24741387
TI  - The Duration of Negative Pressure Wound Therapy Can Be Reduced Using the
      HeartShield Device in Patients With Deep Sternal Wound Infection.
AB  - BACKGROUND: Heart rupture resulting in lethal bleeding is a devastating
      complication associated with negative pressure wound therapy (NPWT) in patients
      with deep sternal wound infection (DSWI). We have previously reported that the
      use of a protective HeartShield device in combination with NPWT decreases the
      risk of damage to the heart. This article presents a retrospective analysis of
      NPWT duration with and without the HeartShield device. SUBJECTS AND PATIENTS: The
      study included 6 patients treated with the HeartShield device in combination with
      NPWT and 6 patients treated with conventional NPWT during the same time period.
      The duration of active treatment time was measured. RESULTS: The median duration
      of NPWT was 8 days (range: 6-14 days) in the HeartShield device NPWT group and 14
      days in the conventional group (range: 10-18 days). The difference was
      statistically significant (P < .05). CONCLUSIONS: It appears that the treatment
      of patients with DSWI with the HeartShield device reduces the duration of NPWT.

PMID- 24741388
TI  - A fungal burn infection.

PMID- 24741389
TI  - Toxic epidermal necrolysis.

PMID- 24741390
TI  - Pai syndrome: median cleft lip, corpus callosum lipoma, and fibroepithelial skin
      tag.

PMID- 24741391
TI  - Diagnosis: chronic osteomyelitis.

PMID- 24741392
TI  - Sequelae following radical parotidectomy: the role of the reconstructive surgeon.

PMID- 24741393
TI  - The Contemporary Role of Echocardiography in Improving Patient Response to
      Cardiac Resynchronization Therapy.
AB  - Cardiac resynchronization therapy (CRT) is an important therapy for heart failure
      patients with widened electrocardiographic QRS complexes and depressed ejection
      fractions, however, approximately one-third do not respond. This article presents
      a practical contemporary approach to the utility of echocardiography to improve
      CRT patient response by assessing mechanical dyssynchrony, optimizing left
      ventricular lead positioning, and performing appropriate echo-Doppler
      optimization, along with future potential roles. Specifically, recent long-term
      outcome data are presented that demonstrates that baseline dyssynchrony is a
      powerful marker associated with CRT response, in particular for patients with
      narrower QRS duration or non left bundle branch block morphology. Advances in
      speckle tracking echocardiography to tailor delivery of CRT by guiding LV lead
      position is discussed, including data from randomized clinical trials supporting
      targeting the LV lead toward the site of latest activation. In addition, an
      update on the current role of Doppler echocardiographic device optimization after
      CRT implantation is reviewed.

PMID- 24741394
TI  - Black rice extract protected HepG2 cells from oxidative stress-induced cell death
      via ERK1/2 and Akt activation.
AB  - BACKGROUND/OBJECTIVES: The objective of this study was to evaluate the protective
      effect of black rice extract (BRE) on tert-butyl hydroperoxide (TBHP)-induced
      oxidative injury in HepG2 cells. MATERIALS/METHODS: Methanolic extract from black
      rice was evaluated for the protective effect on TBHP-induced oxidative injury in
      HepG2 cells. Several biomarkers that modulate cell survival and death including
      reactive oxygen species (ROS), caspase-3 activity, and related cellular kinases
      were determined. RESULTS: TBHP induced cell death and apoptosis by a rapid
      increase in ROS generation and caspase-3 activity. Moreover, TBHP-induced
      oxidative stress resulted in a transient ERK1/2 activation and a sustained
      increase of JNK1/2 activation. While, BRE pretreatment protects the cells against
      oxidative stress by reducing cell death, caspase-3 activity, and ROS generation
      and also by preventing ERKs deactivation and the prolonged JNKs activation.
      Moreover, pretreatment of BRE increased the activation of ERKs and Akt which are
      pro-survival signal proteins. However, this effect was blunted in the presence of
      ERKs and Akt inhibitors. CONCLUSIONS: These results suggest that activation of
      ERKs and Akt pathway might be involved in the cytoprotective effect of BRE
      against oxidative stress. Our findings provide new insights into the
      cytoprotective effects and its possible mechanism of black rice against oxidative
      stress.

PMID- 24741395
TI  - Induction of apoptosis by a hexane extract of aged black garlic in the human
      leukemic U937 cells.
AB  - BACKGROUND/OBJECTIVES: In this study, the apoptogenic activity and mechanisms of
      cell death induced by hexane extract of aged black garlic (HEABG) were
      investigated in human leukemic U937 cells. MATERIALS/METHODS: Cytotoxicity was
      evaluated by MTT (3-(4, 5-dimethyl-thiazol-2-yl)-2, 5-diphenyl
      tetrazoliumbromide) assay. Apoptosis was detected using 4,6-diamidino-2
      phenyllindile (DAPI) staining, agarose gel electrophoresis and flow cytometry.
      The protein levels were determined by Western blot analysis. Caspase activity was
      measured using a colorimetric assay. RESULTS: Exposure to HEABG was found to
      result in a concentration- and time-dependent growth inhibition by induction of
      apoptosis, which was associated with an up-regulation of death receptor 4 and Fas
      legend, and an increase in the ratio of Bax/Bcl-2 protein expression. Apoptosis
      inducing concentrations of HEABG induced the activation of caspase-9, an
      initiator caspase of the mitochodrial mediated intrinsic pathway, and caspase-3,
      accompanied by proteolytic degradation of poly(ADP-ribose)-polymerase. HEABG also
      induced apoptosis via a death receptor mediated extrinsic pathway by caspase-8
      activation, resulting in the truncation of Bid, and suggesting the existence of
      cross-talk between the extrinsic and intrinsic pathways. However, pre-treatment
      of U937 cells with the caspase-3 inhibitor, z-DEVD-fmk, significantly blocked the
      HEABG-induced apoptosis of these cells, and increased the survival rate of HEABG
      treated cells, confirming that HEABG-induced apoptosis is mediated through
      activation of caspase cascade. CONCLUSIONS: Based on the overall results, we
      suggest that HEABG reduces leukemic cell growth by inducing caspase-dependent
      apoptosis through both intrinsic and extrinsic pathways, implying its potential
      therapeutic value in the treatment of leukemia.

PMID- 24741396
TI  - Antioxidative effects of fermented sesame sauce against hydrogen peroxide-induced
      oxidative damage in LLC-PK1 porcine renal tubule cells.
AB  - BACKGROUND/OBJECTIVES: This study was performed to investigate the in vitro
      antioxidant and cytoprotective effects of fermented sesame sauce (FSeS) against
      hydrogen peroxide (H2O2)-induced oxidative damage in renal proximal tubule LLC
      PK1 cells. MATERIALS/METHODS: 1,1-diphenyl-2-picrylhydrazyl (DPPH), hydroxyl
      radical ((*)OH), and H2O2 scavenging assay was used to evaluate the in vitro
      antioxidant activity of FSeS. To investigate the cytoprotective effect of FSeS
      against H2O2-induced oxidative damage in LLC-PK1 cells, the cellular levels of
      reactive oxygen species (ROS), lipid peroxidation, and endogenous antioxidant
      enzymes including catalase (CAT), superoxide dismutase (SOD), and glutathione
      peroxidase (GSH-px) were measured. RESULTS: The ability of FSeS to scavenge DPPH,
      (*)OH and H2O2 was greater than that of FSS and AHSS. FSeS also significantly
      inhibited H2O2-induced (500 uM) oxidative damage in the LLC-PK1 cells compared to
      FSS and AHSS (P < 0.05). Following treatment with 100 ug/mL of FSeS and FSS to
      prevent H2O2-induced oxidation, cell viability increased from 56.7% (control) to
      83.7% and 75.6%, respectively. However, AHSS was not able to reduce H2O2-induced
      cell damage (viability of the AHSS-treated cells was 54.6%). FSeS more
      effectively suppressed H2O2-induced ROS generation and lipid peroxidation
      compared to FSS and AHSS (P < 0.05). Compared to the other sauces, FSeS also
      significantly increased cellular CAT, SOD, and GSH-px activities and mRNA
      expression (P < 0.05). CONCULUSIONS: These results from the present study suggest
      that FSeS is an effective radical scavenger and protects against H2O2-induced
      oxidative damage in LLC-PK1 cells by reducing ROS levels, inhibiting lipid
      peroxidation, and stimulating antioxidant enzyme activity.

PMID- 24741397
TI  - Naringenin stimulates cholecystokinin secretion in STC-1 cells.
AB  - BACKGROUND/OBJECTIVES: Cholecystokinin (CCK), a hormone or neuropeptide, is
      secreted in response to intraluminal nutrients by enteroendocrine I-cells of the
      intestine and has important physiological actions related to appetite regulation
      and satiety. The stimulation on CCK secretion from the intestine is of potential
      relevance for body weight management. Naringenin (4',5,7-trihydroxyflavanone) and
      its glycoside naringin (naringenin 7-rhamnoglucoside) have been reported to have
      many biological functions. In the current study, we investigated the question of
      whether naringenin and naringin could stimulate CCK secretion and then examined
      the mechanisms involved in CCK release. MATERIALS/METHODS: STC-1 cells were used
      as a model of enteroendocrine cells. CCK release and changes in intracellular
      Ca(2+) ([Ca(2+)]i) were measured after incubation of cells with naringenin and
      naringin for 1 h. RESULTS: Naringenin caused significant (P < 0.05) stimulation
      of CCK secretion, but naringin did not. In addition, regarding the secretory
      mechanisms, naringenin-induced CCK secretion involved increases in [Ca(2+)]i,
      influx of extracellular Ca(2+), at least in part, and activation of TRP channels,
      including TRPA1. CONCLUSION: Findings of this study suggest that naringenin could
      have a role in appetite regulation and satiety.

PMID- 24741398
TI  - In vitro biological evaluation of 100 selected methanol extracts from the
      traditional medicinal plants of Asia.
AB  - BACKGROUND/OBJECTIVES: In Asia, various medicinal plants have been used as the
      primary sources in the health care regimen for thousands of years. In recent
      decades, various studies have investigated the biological activity and potential
      medicinal value of the medicinal plants. In this study, 100 methanol extracts
      from 98 plant species were evaluated for their biological activities.
      MATERIALS/METHODS: The research properties, including 1,1-diphenyl-2-pic
      rylhydrazyl (DPPH) radical scavenging activity, alpha-glucosidase and alpha
      tyrosinase inhibitory effects, anti-inflammatory activity, and anticancer
      activity were evaluated for the selected extracts. RESULTS: Fifteen of the
      extracts scavenged more than 90% of the DPPH radical. Among the extracts,
      approximately 20 extracts showed a strong inhibitory effect on alpha-glucosidase,
      while most had no effect on alpha-tyrosinase. In addition, 52% of the extracts
      showed low toxicity to normal cells, and parts of the extracts exhibited high
      anti-inflammatory and anticancer activities on the murine macrophage cell (RAW
      264.7) and human colon cancer cell (HT-29) lines, respectively. CONCLUSIONS: Our
      findings may contribute to further nutrition and pharmacological studies.
      Detailed investigations of the outstanding samples are currently underway.

PMID- 24741399
TI  - Peanut sprouts extract (Arachis hypogaea L.) has anti-obesity effects by
      controlling the protein expressions of PPARgamma and adiponectin of adipose
      tissue in rats fed high-fat diet.
AB  - BACKGROUD/OBEJECTIVES: This study aims to find out the effects of peanut sprout
      extracts on weight controls and protein expressions of transcription factors
      related to adipocyte differentiation and adipocytokine in rats under high-fat
      diets. MATERIALS/METHODS: Four week-old Sparague-Dawley (SD) were assigned to 4
      groups; normal-fat (NF) diets (7% fat diet), high-fat (HF) diets (20% fat diet),
      high fat diets with low peanut sprout extract (HF + PSEL) diet (20% fat and
      0.025% peanut sprout extract), and high fat diets with high peanut sprout extract
      (HF + PSEH) diet (20% fat and 0.05% peanut sprout extract). Body weight changes,
      lipid profiles in adipose tissue, and the mRNA protein expressions, such as
      peroxisome proliferator-activated receptor gamma (PPARgamma), CCAAT element
      binding protein alpha (C/EBP alpha), leptin, and adiponectin, were determined.
      RESULTS: After 9 weeks of feeding, the HF + PSEH group had significantly less
      weight gains than the HF group (P < 0.05). However, the total dietary intakes or
      food efficiency ratios among groups were not significantly different. The weight
      of epididymal fat in HF + PSEH group, 3.61 +/- 0.5 g, or HF + PSEL group, 3.80 +/
      0.7 g, was significantly lower than the HF group, 4.39 +/- 0.4g, (P < 0.05).
      Total lipids and total cholesterol in adipose tissue were significantly decreased
      in HF + PSEH group compared to those in the HF group, respectively (P < 0.05).
      PSEH supplementation caused AST and ALT levels to decrease when it compared to HF
      group, but it was not statistically significant. The protein expression of
      PPARgamma in HF + PSEH group was significantly lower than the HF group (P <
      0.05). Comparing with the HF group, the protein expression of adiponectin in HF +
      PSEH group was significantly increased (P < 0.05). The protein expressions of
      C/EBP alpha and leptin in HF + PSEH group were lower than the HF group, but it
      was not statistical significant. CONCLUSIONS: In conclusion, peanut sprout
      extract has anti-obesity effect by lowering the expressions of PPARgamma which
      regulates the expression of adiponectin.

PMID- 24741400
TI  - Beneficial effects of natural Jeju groundwaters on lipid metabolism in high-fat
      diet-induced hyperlipidemic rats.
AB  - BACKGROUND: Groundwater is believed to possess many beneficial effects due to its
      natural source of various minerals. In this study, we examined the effects of
      natural Jeju groundwater S1 (SamdasooTM), S2 and S3 pumped up from different
      locations of Jeju Island, Korea, along with local tap water, on body weight gain,
      serum lipids and lipoproteins, and liver histopathology in high-fat diet-induced
      hyperlipidemic rats. MATERIALS/METHODS: Rats were randomly and equally divided
      into 6 groups. Different water samples were supplied to the hyperlipidemic rats
      as their daily drinking water and the widely-used anti-hyperlipidemic drug
      simvastatin was used as a positive control. Body weight, serum lipids and
      lipoproteins were measured weekly. Liver weight, liver index and liver
      histopathology were examined after the execution of the rats. RESULTS: After
      drinking Jeju groundwaters for two months, S2 but not S3 significantly reduced
      weight growth and serum triglycerides levels and increased high density
      lipoprotein-C (HDL-C) without affecting total cholesterol or LDL-C. S1 and
      particularly S2 significantly reduced the severity of liver hypertrophy and
      steatosis. All Groundwaters had much higher contents of vanadium (S3>S2>S1>>tap
      water) whereas S1 and S2 but not S3 markedly blocked autoxidation of ferrous
      ions. CONCLUSION: Jeju Groundwater S1 and particularly S2 exhibit protective
      effects against hyperlipidemia and fatty liver and hypothesize that the
      beneficial effect of Jeju Groundwaters may be contributed from blockade of
      autoxidation of ferrous ions rather than their high contents of vanadium.

PMID- 24741401
TI  - Cordyceps militaris alleviates non-alcoholic fatty liver disease in ob/ob mice.
AB  - BACKGROUND/OBJECTIVES: Non-alcoholic fatty liver disease (NAFLD) is becoming an
      important public health problem as metabolic syndrome and type 2 diabetes have
      become epidemic. In this study we investigated the protective effect of Cordyceps
      militaris (C. militaris) against NAFLD in an obese mouse model.
      MATERIALS/METHODS: Four-week-old male ob/ob mice were fed an AIN-93G diet or a
      diet containing 1% C. militaris water extract for 10 weeks after 1 week of
      adaptation. Serum glucose, insulin, free fatty acid (FFA), alanine transaminase
      (ALT), and proinflammatory cytokines were measured. Hepatic levels of lipids,
      glutathione (GSH), and lipid peroxide were determined. RESULTS: Consumption of C.
      militaris significantly decreased serum glucose, as well as homeostasis model
      assessment for insulin resistance (HOMA-IR), in ob/ob mice. In addition to
      lowering serum FFA levels, C. militaris also significantly decreased hepatic
      total lipids and triglyceride contents. Serum ALT activities and tumor necrosis
      factor-alpha (TNF-alpha) and interleukin-6 (IL-6) levels were reduced by C.
      militaris. Consumption of C. militaris increased hepatic GSH and reduced lipid
      peroxide levels. CONCLUSIONS: These results indicate that C. militaris can exert
      protective effects against development of NAFLD, partly by reducing inflammatory
      cytokines and improving hepatic antioxidant status in ob/ob mice.

PMID- 24741402
TI  - Effects of aged garlic extract and endurance exercise on skeletal muscle FNDC-5
      and circulating irisin in high-fat-diet rat models.
AB  - BACKGROUND/OBJECTIVES: Irisin, a newly identified hormone, is associated with
      energy homeostasis. We investigated whether aged garlic extract (AGE) and
      exercise training intervention could improve body weight, insulin sensitivity,
      skeletal muscle fibronectin domain containing protein 5 (FNDC-5) levels, and
      plasma irisin in high-fat diet (HFD). MATERIALS/METHODS: Male Sprague Dawley rats
      were fed a ND (normal diet, n = 5) or HFD (n = 28) for 6 weeks. After 6 weeks,
      all rats were divided into 5 groups for the next 4 weeks: ND, (normal diet, n =
      5), HFD (high-fat diet, n = 7), HFDA (high-fat diet + aged garlic extract, n =
      7), HFDE (high-fat diet + exercise, n = 7), and HFDEA (high-fat diet + exercise +
      aged garlic extract, n = 7). Exercise groups performed treadmill exercises for 15
      60 min, 5 days/week, and AGE groups received AGE (2.86 g/kg, orally injected) for
      4 weeks. RESULTS: Significant decreases in body weight were observed in the ND,
      HFDE, and HFDEA groups, as compared with the HFD group. Neither intervention
      affected the masses of the gastrocnemius muscle or liver. There were no
      significant differences in glucose levels across the groups. The homeostatic
      model assessments of insulin resistance were significantly higher in the HFD
      group, as compared with the ND, HFDA, HFDE, and HFDEA groups. However, skeletal
      muscle FNDC-5 levels and plasma irisin concentrations were unaffected by AGE or
      exercise in obese rats. AGE supplementation and exercise training did not affect
      skeletal muscle FNDC-5 or plasma irisin, which are associated with insulin
      sensitivity in obese rats. CONCLUSION: Our results suggest that the protection
      against HFD-induced increases in body fat/weight and insulin resistance that are
      provided by AGE supplementation and exercise training may not be mediated by the
      regulation of FNDC-5 or irisin.

PMID- 24741403
TI  - Total antioxidant capacity of the Korean diet.
AB  - BACKGROUND/OBJECTIVES: The objective of this study was to measure and/or estimate
      the total antioxidant capacity of the Korean diet. MATERIALS/METHODS: Eighty-one
      plant foods that were expected to exhibit rather high antioxidant activities were
      selected from the Korean diet using the Fifth Korean National Health and
      Nutrition Survey (KNHANES V). These foods were categorized into 11 food groups:
      cereals, potatoes, legumes, nuts, vegetables, kimchies, mushrooms, fruits, fruit
      juices, sea weeds, and oils. The foods were mixed in the proportions specified in
      traditional Korean recipes and analyzed. The measured indicators for antioxidant
      capacities were total phenolics, 2,2-diphenyl-1-picrylhydrazyl (DPPH), oxygen
      radical absorbance capacity (ORAC), and Trolox equivalent antioxidant capacity
      (TEAC). RESULTS: Total phenolics were high in the fruit juices, nuts, vegetables,
      and fruits; and the average DPPH, ORAC, and TEAC values were high in the
      vegetables, fruits, fruit juices, and nuts. The correlation coefficient between
      the content of total phenolics of each food and the in vitro antioxidant capacity
      was relatively high at 0.851. The intake of total phenolics per capita per day in
      the Republic of Korea was estimated to be 127 mg. The total dietary antioxidant
      capacity (TDAC) values, which were obtained from the total antioxidant capacity
      of each food, taking into account the intake of each food, were 20,763, 54,335,
      and 876.4 umol of Trolox equivalents using the DPPH, ORAC, and TEAC methods,
      respectively. The food group that contributed the most to the Korean TDAC was
      cereals at 39.7%, followed by fruits and vegetables at 27.8% and 13.9%,
      respectively. The contribution of legumes, nuts, fruit juices, and mushrooms was
      quite minimal at less than 2% each. CONCLUSIONS: The content of total phenolics
      and the antioxidant capacity of the Korean diet are significantly correlated and
      the high contributing food groups are cereals, fruits, and vegetables.

PMID- 24741404
TI  - Dietary pattern classifications with nutrient intake and body composition changes
      in Korean elderly.
AB  - BACKGROUND/OBJECTIVES: The body composition changes in aging increased the risk
      of metabolic disorder. Recent dietary studies have increasingly focused on the
      correlations between dietary patterns and chronic diseases to overcome the
      limitations of traditional single-nutrient studies because nutrients in food have
      complex relations that interact. SUBJECTS/METHODS: This study was conducted to
      classify a dietary pattern among Korean elderly using cluster analysis and to
      explore the relationships between dietary patterns and body composition changes
      in Korean elderly aged 65 years or older. The study subjects (n = 1,435) were
      individuals who participated in the Korean National Health Examination and
      Nutrition Survey (KNHANES) in 2011. RESULTS: THERE WERE THREE DIETARY PATTERNS
      DERIVED BY CLUSTER ANALYSIS IN THIS STUDY: 'Traditional Korean' (37.49% of total
      population), 'Meat and Alcohol' (19.65%) and 'Westernized Korean' (42.86%). The
      (1) 'Traditional Korean' pattern was characterized by high consumptions of white
      rice and low protein, low fat, and low milk products, while (2) 'Westernized
      Korean' pattern ate a Korean-style diet base with various foods such as noodles,
      bread, eggs and milk, (3) 'Meat and Alcohol' pattern had high consumptions of
      meat and alcohol. In body composition changes, compared with the 'Traditional
      Korean' pattern, the 'Meat & alcohol' pattern was associated with a 50% increased
      risk of having elevated BMI (kg/m(2)), 'Westernized Korean' pattern was
      associated with a 74% increased abnormality of ASM/Wt (kg) by logistics analysis.
      Most of the Korean adult population continues to follow ether a traditional
      Korean having beneficial effects for successful aging. However, the 'Traditional
      Korean' pattern showed low protein intake (0.7 g/kg), calcium intake, and vitamin
      D intake as well as low of appendicular skeletal muscle mass (ASM (kg)) among 3
      groups. CONCLUSIONS: Considering the low ASM, consumption of protein, calcium and
      vitamin D should be increased for Korean elderly health body composition.

PMID- 24741405
TI  - Food security experiences of displaced North Korean households.
AB  - BACKGROUND/OBJECTIVES: Food shortage situation in North Korea has gained much
      interest, however food insecurity caused by the food shortage in North Korean
      households has not been much investigated. This study examined food security
      experiences and food consumption pattern of displaced North Korean households
      currently living in South Korea. SUBJECTS/METHODS: Food security experience among
      51 North Korean households living in South Korea was examined using the Household
      Food Insecurity Access Scale (HFIAS) in three time points: immediately before
      childbirth, immediately before leaving North Korea, and immediately before
      entering South Korea. Meal/snack consumption frequencies and food diversity were
      also examined. RESULTS: Food security situation was the worst at the time of
      immediately before leaving North Korea with the average HFIAS score of 10.05. The
      households that were food insecure, they tended to be "severely" insecure.
      Although majority of the subjects reported having three or more meals a day, food
      diversity in their diet was very low with the average food diversity score of
      2.17 immediately before childbirth and 1.74 immediately before leaving North
      Korea. Their diet appeared to heavily rely on grain and vegetable. CONCLUSIONS:
      This study is one of few that specifically examined food security of North Korean
      households with a pre-developed scale, and that demonstrated food security
      situation at different time points in quantified terms. Replicating this study
      with different groups of North Korean households for different time points would
      allow more complete understanding of impacts of food shortage. Food diversity
      score could provide a good way to examine changes of food consumption occurring
      to North Koreans in the process of adaptation. More attention to the changes
      occurring during adaption to South Korea should be given to understand the
      process and impact and to prepare public nutrition policy for the re-unified
      Korea.

PMID- 24741406
TI  - A comparative study on dietary behavior, nutritional knowledge and life stress
      between Korean and Chinese female high school students.
AB  - BACKGROUND/OBJECTIVES: Dietary behavior and life stress in adolescence is related
      to growth rate and learning ability. This study was conducted to identify the
      relations between dietary habits, dietary attitude nutritional knowledge and life
      stress among high school girls in Korea and China. SUBJECTS/METHODS: The subjects
      of this study were 221 high school girls in Korea and 227 high school girls in
      China. The questionnaire were about dietary habits, dietary attitude, nutritional
      knowledge and life stress. RESULTS: The dietary habits of chinese girls were
      healthier than those of Korean girls with a significant difference (P < .001).
      There was no significant difference in dietary attitude between Korean girls and
      Chinese girls. Korean girls had more nutritional knowledge than Chinese girls
      with a significant difference (P < .001). Korean girls did less physical exercise
      but spent more time watching TV and using PCs, compared to Chinese girls. Korean
      girls' degree of confidence in nutrition information that they had learned and
      their performance in their real lives were low. Also, they had a low level of
      awareness of the need for nutritional education. There was no significant
      difference in life stress between the two groups. Dietary habits had a
      significantly negative correlation with life stress in both Korean and Chinese
      girls (P < .01, P < .001). As for Chinese students, dietary attitude had a
      negative correlation with life stress with a significant difference (P < .05). As
      for Korean girls, nutritional knowledge had a negative correlation with life
      stress with a significant difference (P < .05), which means as life stress was
      less, dietary habits were better. CONCLUSIONS: This study shows that effective
      nutrition education programs should include components that encourage application
      of learned nutrition information to real life, increase physical exercise and
      reduce life stress.

PMID- 24741407
TI  - Weight misperception and its association with dieting methods and eating
      behaviors in South Korean adolescents.
AB  - BACKGROUND/OBJECTIVES: There is little information on the association between
      weight misperception and eating behavior in Korean adolescents. Therefore, we
      investigated the association of food intake habits and dieting method and
      disturbed eating behavior (DEB) in relation to weight misperception.
      SUBJECTS/METHODS: Data was collected by using a nationwide online panel survey
      from 6,943 adolescents enrolled in middle/high school. DEB was measured with the
      Eating Attitudes Test (EAT-26) and those who scored >= 20 on the EAT-26 were
      considered to have eating disorder. Logistic regressions were conducted to
      examine the association between weight misperception based on self-reported
      weight status and dieting method and eating behaviors. RESULTS: The proportion of
      weight underestimation was 23.5% and that of overestimation was 24.0%. Weight
      overestimating girls were more likely to engage in various unhealthy dieting
      practices (OR = 1.69 for fasting; OR = 1.88 for laxative or diuretic use; OR =
      2.05 for self-induced vomiting after meals; P < 0.05). Moreover, there was a
      strong association between overestimation and undesirable eating behaviors,
      especially among girls, e.g.: having breakfast (OR = 0.85), high consumption of
      fast foods (OR = 1.28) and regular sodas (OR = 1.39), but not among boys. In both
      genders, weight overestimation appears to be a major risk factor for DEB (OR =
      1.34 for boys and OR = 1.41 for girls; P < 0.05). CONCLUSIONS: [corrected] Weight
      overestimation is associated with unhealthy weight control practices and eating
      behaviors. We particularly found a significant association between weight
      overestimation and DEB among nationwide Korean adolescents.

PMID- 24741408
TI  - Protective effect of resveratrol on arsenic trioxide-induced nephrotoxicity in
      rats.
AB  - BACKGROUD/OBEJECTIVES: Arsenic, which causes human carcinogenicity, is ubiquitous
      in the environment. This study was designed to evaluate modulation of arsenic
      induced cancer by resveratrol, a phytoalexin found in vegetal dietary sources
      that has antioxidant and chemopreventive properties, in arsenic trioxide (As2O3)
      induced Male Wistar rats. MATERIALS/METHODS: Adult rats received 3 mg/kg As2O3
      (intravenous injection, iv.) on alternate days for 4 days. Resveratrol (8 mg/kg)
      was administered (iv.) 1 h before As2O3 treatment. The plasma and homogenization
      enzymes associated with oxidative stress of rat kidneys were measured, the
      kidneys were examined histologically and trace element contents were assessed.
      RESULTS: Rats treated with As2O3 had significantly higher oxidative stress and
      kidney arsenic accumulation; however, pretreatment with resveratrol reversed
      these changes. In addition, prior to treatment with resveratrol resulted in lower
      blood urea nitrogen, creatinine and insignificant renal tubular epithelial cell
      necrosis. Furthermore, the presence of resveratrol preserved the selenium content
      (0.805 +/- 0.059 ug/g) of kidneys in rats treated with As2O3. However,
      resveratrol had no effect on zinc level in the kidney relative to As2O3-treated
      groups. CONCLUSIONS: Our data show that supplementation with resveratrol
      alleviated nephrotoxicity by improving antioxidant capacity and arsenic efflux.
      These findings suggest that resveratrol has the potential to protect against
      kidney damage in populations exposed to arsenic.

PMID- 24741409
TI  - Dilemmas over the decision to perform repeat prostate biopsies.

PMID- 24741410
TI  - Treatment of bladder dysfunction using stem cell or tissue engineering technique.
AB  - Tissue engineering and stem cell transplantation are two important options that
      may help overcome limitations in the current treatment strategy for bladder
      dysfunction. Stem cell therapy holds great promise for treating pathophysiology,
      as well as for urological tissue engineering and regeneration. To date, stem cell
      therapy in urology has mainly focused on oncology and erectile dysfunction. The
      therapeutic potency of stem cells (SCs) was originally thought to derive from
      their ability to differentiate into various cell types including smooth muscle.
      The main mechanisms of SCs in reconstituting or restoring bladder function are
      migration, differentiation, and paracrine effects. Nowadays, paracrine effects of
      stem cells are thought to be more prominent because of their stimulating effects
      on stem cells and adjacent cells. Studies of stem cell therapy for bladder
      dysfunction have been limited to experimental models and have been less focused
      on tissue engineering for bladder regeneration. Bladder outlet obstruction is a
      representative model. Adipose-derived stem cells, bone marrow stem cells (BMSCs),
      and skeletal muscle-derived stem cells or muscle precursor cells are used for
      transplantation to treat bladder dysfunction. The aim of this study is to review
      stem cell therapy and updated tissue regeneration as treatments for bladder
      dysfunction and to provide the current status of stem cell therapy and tissue
      engineering for bladder dysfunction including its mechanisms and limitations. 

PMID- 24741411
TI  - Relating prognosis in chromophobe renal cell carcinoma to the chromophobe tumor
      grading system.
AB  - PURPOSE: The chromophobe subtype of renal cell carcinoma (chRCC) has generally
      been associated with a better prognosis than the clear cell type; however, debate
      continues as to absolute prognosis as well as the significance of certain
      prognostic variables. We investigated the significance of pathologic stage and a
      recently proposed chromophobe tumor grading (CTG) scheme in predicting chRCC
      outcomes. MATERIALS AND METHODS: All available chRCCs were identified from our
      surgical pathology archives from 1987-2010. Original slides were reviewed to
      verify diagnoses and stage, and each case was graded following a novel
      chromophobe tumor grade system criteria. Disease status was obtained from a
      clinical outcome database, and cancer specific deaths and recurrences were
      recorded. RESULTS: Eighty-one cases of chRCC were identified, and 73 had adequate
      follow-up information available. There were only 3 instances of cancer related
      recurrence or mortality, which included 1 disease specific mortality and 2
      disease recurrences. Pathologic stage and CTG 3 were found to be significantly
      associated with the recurrences or death from chRCC, but there was no association
      with CTG 1 and CTG 2. CONCLUSIONS: chRCC is associated with a very low rate of
      cancer specific events (4.1%) even at a tertiary referral center. In our study,
      pathologic stage and CTG 3, but not CTG 1 or 2, were significantly associated
      with the development of these events.

PMID- 24741412
TI  - Detection rate of prostate cancer on the basis of the vienna nomogram: a
      singapore study.
AB  - PURPOSE: The purpose of this study was to determine the efficacy of the Vienna
      nomogram prostate biopsy model in the detection of prostate cancer in our local
      population. We also assessed the incidence of complications from using such a
      template. MATERIALS AND METHODS: From January 2006 to June 2007, 120 men with
      either elevated prostate-specific antigen (PSA) scores (>4 ng/mL) and/or abnormal
      digital rectal examination were enrolled prospectively to undergo extraction of 6
      to 18 cores for transrectal ultrasound-guided prostate biopsy, as indicated by
      the Vienna nomogram. RESULTS: The mean age was 62.6+/-8.3 years (range, 40-86
      years). The mean PSA score was 13.42 ng/mL. The mean number of cores obtained was
      9.68+/-3.1. According to the Vienna nomogram, 27 out of a total of 120 patients
      had prostate cancer, for a detection rate of 22.5%. In the group of patients with
      PSA scores <10 ng/mL, the detection rate was 14.9% (14 of 94 patients). The group
      of patients with PSA scores >10 ng/mL had a detection rate of 50% (13 of 26). The
      complication rate in our study was 7.5%. CONCLUSIONS: With the use of the Vienna
      nomogram, our prostate cancer detection rate is comparable to previously
      published data for Asian patients. This nomogram offers an easy tool with which
      to select the optimal number of prostate biopsy cores to be taken on the basis of
      patient age and total prostate volume. With this biopsy strategy, we also have
      found that the complication rate from prostate biopsy is low.

PMID- 24741413
TI  - Efficacy of Repeated Transrectal Prostate Biopsy in Men Younger Than 50 Years
      With an Elevated Prostate-Specific Antigen Concentration (>3.0 ng/mL): Risks and
      Benefits Based on Biopsy Results and Follow-up Status.
AB  - PURPOSE: Prostate cancer is rare in men younger than 50 years. Digital rectal
      examination (DRE) and measurement of prostate-specific antigen (PSA)
      concentrations are standard screening methods for detecting prostate cancer. We
      retrospectively investigated the risks and benefits of repeated transrectal
      ultrasonography-guided prostate needle biopsies in relation to the follow-up
      status of men younger than 50 years with a consistently high PSA concentration
      (>3.0 ng/mL). MATERIALS AND METHODS: During the period from January 2000 through
      February 2013, we reviewed patient's ages, dates of procedures, DRE results,
      frequencies of biopsies, results of the biopsies, periods of follow-up, PSA
      concentrations, and prostate volumes in Chonbuk National University Hospital
      records. We conducted telephone interviews in patients who did not undergo
      regular follow-up. RESULTS: The mean age of the patients was 44.7 years, and the
      mean PSA concentration was 8.59 ng/mL (range, 3.04-131 ng/mL) before biopsy. The
      PSA concentration was significantly different (p<0.001) between the patients with
      prostate cancer and those with benign prostatic hyperplasia (BPH). Nineteen
      patients underwent repeated prostate biopsy; however, in only one patient did the
      pathologic findings indicate a change from BPH to prostate cancer. We identified
      several complications after transrectal biopsy through an evaluation of follow-up
      data. CONCLUSIONS: All patients with benign prostatic disease based on their
      first biopsy were shown to have benign disease based on all repeated biopsies
      (15.83%), except for one patient; however, several complications were noted after
      biopsy. Therefore, the risks and benefits of repeated biopsy in young patients
      should be considered because of the low rate of change from benign to malignant
      disease despite continuously high PSA concentrations (>3.0 ng/mL).

PMID- 24741414
TI  - The nephrometry score: is it effective for predicting perioperative outcome
      during robot-assisted partial nephrectomy?
AB  - PURPOSE: Robot-assisted partial nephrectomy (RPN) has emerged as an alternative
      treatment for the management of small renal masses. This study was designed to
      investigate parameters that predict perioperative outcomes during RPN. MATERIALS
      AND METHODS: We retrospectively reviewed the medical records of 113 patients who
      underwent RPN between September 2008 and May 2012 at the Seoul National
      University Bundang Hospital. Clinical parameters, including warm ischemia time
      (WIT), estimated blood loss (EBL), and R.E.N.A.L and PADUA scores, were evaluated
      to predict perioperative outcomes. RESULTS: Of the 113 patients, 81 were men and
      32 were women. The patients' mean age was 53.5 years, and their mean body mass
      index was 22.3 kg/m(2). Age, gender, and mass laterality had no effect on
      perioperative complications, WIT, or EBL. Univariate analysis revealed that a
      distance between the tumor and the collecting system of <=4 mm or a renal mass
      size of >4 cm were associated with adverse profiles of complications, WIT, and
      EBL. However, multivariate analysis showed no association between the predictive
      parameters and tumor complexity as assessed by nephrometry scores. Tumor size of
      >4 cm increased the risk of blood loss >300 mL (odds ratio [OR], 3.5; 95%
      confidence interval [CI], 1.3.9.7; p=0.016). A distance between the tumor and the
      collecting system of <=4 mm was associated with increased risk of WIT exceeding
      20 minutes (OR, 2.8; 95% CI, 1.3.6.3; p=0.012). CONCLUSIONS: Tumor size and
      proximity of the mass to the collecting system showed significant associations
      with EBL and WIT, respectively, during RPN. The R.E.N.A.L and PADUA nephrometry
      scoring systems did not predict perioperative outcomes.

PMID- 24741415
TI  - Tolterodine to relieve urinary symptoms following transurethral resection of the
      prostate: a double-blind placebo-controlled randomized clinical trial.
AB  - PURPOSE: To evaluate the effect of tolterodine on early storage symptoms
      following transurethral resection of the prostate. MATERIALS AND METHODS: Seventy
      patients over 55 years of age who underwent transurethral resection of the
      prostate owing to benign prostatic hyperplasia were randomly assigned to receive
      either 2 mg of tolterodine twice daily (treatment group) or matched placebo
      during a 1-month study period. Before and 1 month after the procedure, they were
      asked to complete the International Prostate Symptom Score (IPSS) questionnaire
      and quality of life subscale to assess their symptoms. Also, analgesic use and
      adverse drug events were determined at follow-up. RESULTS: Of 70 allocated
      patients, 64 patients (91.4%), including 33 in the treatment group and 31 in the
      placebo group, completed the study. The mean age of the patients was 67 years.
      None of the patients' basic clinical characteristics were significantly
      different. At the end of the follow-up period, the total IPSS and quality of life
      score had significantly improved in the patients receiving tolterodine compared
      with those receiving placebo (p=0.001 and p=0.036, respectively). The treatment
      group compared with placebo demonstrated significant improvements in frequency
      and urgency but not in nocturia. The amount of consumed painkiller was also
      significantly lower in the tolterodine group than in the placebo group
      (p=0.0001). The rate of side effects was not significantly different between the
      groups. CONCLUSIONS: Administering 2 mg of tolterodine twice daily is an
      effective and well-tolerated regimen to relieve early storage symptoms, quality
      of life, and the amount of analgesic consumption following transurethral
      resection of the prostate.

PMID- 24741416
TI  - Transobturator tape for female stress urinary incontinence: preoperative valsalva
      leak point pressure is not related to cure rate or quality of life improvement.
AB  - PURPOSE: We investigated whether the Valsalva leak point pressure (VLPP) is
      valuable for predicting postoperative outcome measurement after transobturator
      suburethral tape (TVT-O) implantation for treating stress urinary incontinence
      (SUI) in women. MATERIALS AND METHODS: A total of 204 female patients who
      underwent TVT-O placement for treatment of SUI from March 2008 to February 2012
      were enrolled in this retrospective study. All patients completed the
      incontinence quality of Life questionnaire (I-QoL), a self-reported quality of
      life measure specific to urinary incontinence, and the cure rate of incontinence
      was measured before and 6 months after surgery. Cure was defined as no leakage of
      urine postoperatively both subjectively and objectively. We compared pre- and
      postoperative I-QoL scores according to preoperative VLPP and Stamey grade.
      RESULTS: The numbers of patients with Stamey grades I, II, and III were 99
      (48.5%), 84 (41.2%), and 21 (10.3%), respectively. A total of 30 (14.7%), 87
      (42.6%), and 87 patients (42.6%) showed VLPP<=60, 60<VLPP<=90, and VLPP>90 cm
      H2O, respectively. Preoperative VLPP was not significantly different according to
      preoperative I-QoL or change in I-QoL after surgery. However, I-QoL after surgery
      improved in patients with a high preoperative Stamey grade (p=0.001).
      CONCLUSIONS: VLPP was not a factor related to surgical outcome from the
      midurethral sling procedure. Stamey grade rather than VLPP was important for
      predicting subjective quality of life and improved incontinence-related quality
      of life after surgery.

PMID- 24741417
TI  - Clinical Efficacy of Ertapenem for Recurrent Cystitis Caused by Multidrug
      Resistant Extended-Spectrum beta-Lactamase-Producing Escherichia coli in Female
      Outpatients.
AB  - PURPOSE: To evaluate the clinical outcomes of ertapenem administered as an
      outpatient parenteral antibiotic therapy for intractable cystitis caused by
      extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli. MATERIALS AND
      METHODS: We retrospectively reviewed a case series of 3 years of therapeutic
      experience with ertapenem for intractable recurrent cystitis caused by ESBL
      producing E. coli. Ertapenem 1 g/d was parenterally administered to the patients
      on an outpatient basis until the acquisition of symptomatic improvement and
      negative conversion of urine culture. Demographic and clinical characteristics of
      patients, antimicrobial resistance, and clinical response data were analyzed from
      the patients' medical records. RESULTS: During the course of this study, a total
      of 383 patients were diagnosed with cystitis, and 24 of them showed ESBL
      producing E. coli (6.26%). The mean treatment duration of all patients was 8.5
      days. The early clinical and microbiological cure rates 0 to 7 days after the end
      of treatment were 91.7% (22/24) and 90.9% (20/22), respectively. The late
      clinical and microbiological cure rates 4 to 6 weeks after the end of treatment
      were 72.2% (13/18) at both time points. CONCLUSIONS: Parenteral ertapenem
      treatment can be an effective and well-tolerated treatment option for intractable
      recurrent cystitis by multidrug-resistant ESBL-producing E. coli.

PMID- 24741418
TI  - Clinical significance of national institutes of health classification in patients
      with chronic prostatitis/chronic pelvic pain syndrome.
AB  - PURPOSE: We determined the effects of alpha-blockers and quinolone in patients
      with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) classified by
      National Institute of Health (NIH) consensus group. MATERIALS AND METHODS: Data
      from a total of 111 patients who were diagnosed with CP/CPPS between June 2010
      and June 2012 were analyzed retrospectively. The patients were classified into
      group 1 (category IIIA, n=40) and group 2 (category IIIB, n=71). Treatment using
      alfuzosin and levofloxacin was given to both groups for 6 weeks. International
      Prostate Symptom Score (IPSS) and NIH Chronic Prostatitis Symptom Index were
      measured before and after therapy. RESULTS: Group 1 had a significant decrease in
      total IPSS score, CPSI pain score, CPSI quality of life (QoL) score, and total
      CPSI score (p=0.043, p=0.006, p=0.015, and p=0.006, respectively). Group 2 had a
      significant decrease in IPSS voiding symptom score, IPSS storage symptom score,
      total IPSS, CPSI pain score, CPSI voiding score, CPSI QoL score, and total CPSI
      score (p=0.002, p=0.004, p=0.001, p=0.001, p=0.006, p=0.001, and p=0.001,
      respectively). The CPSI score was reduced by 6 points or more in 50.0% of
      patients (n=18) in group 1 and in 51.6% of patients (n=32) in group 2. However,
      there was no statistically significant difference between the changes in IPSS and
      CPSI scores across the 2 groups. CONCLUSIONS: Although combination treatment
      reduced the CPSI score in both groups, there was no significant difference
      between the groups after combination treatment. We suggest that factors other
      than inflammation also contribute to symptoms associated with CP/CPPS.

PMID- 24741419
TI  - Intradetrusor Injections of Onabotulinum Toxin-A in Children With Urinary
      Incontinence due to Neurogenic Detrusor Overactivity Refractory to Antimuscarinic
      Treatment.
AB  - PURPOSE: This was a prospective single-arm study to assess the efficacy and
      safety of intradetrusor injections of onabotulinum toxin-A in children with
      urinary incontinence associated with neurogenic detrusor overactivity due to
      myelomeningocele. All patients had failed the first-line treatment of a
      combination of oral antimuscarinics and intermittent catheterization. MATERIALS
      AND METHODS: The study group consisted of 31 children with myelomeningocele with
      a mean age of 7.95 years (range, 5-3 years) who were followed up for a mean of 29
      weeks. The amount of onabotulinum toxin A injected was 10 U/kg with a maximal
      dose of 300 U. There were 20 to 30 injection sites with rigid cystoscopic
      guidance under general anesthesia. RESULTS: Thirty of 31 patients reported
      dryness between intermittent catheterization intervals. The mean reduction in
      maximum detrusor pressure and the mean increase in maximum cystometric capacity
      from baseline were 53% and 51.5%, respectively, 6 weeks after injection. We found
      a 324% increase in mean bladder compliance and a 57% increase in mean
      intermittent catheterization volumes. The mean duration of efficacy was 28 weeks
      with a single injection and 36 weeks for repeated injections (minimum, 16 weeks;
      maximum, 52 weeks). The mean time interval between repeated onabotulinum toxin-A
      injections was 7 months (maximum, 13 months). Intradetrusor injections of
      onabotulinum toxin-A were well tolerated. CONCLUSIONS: Onabotulinum toxin-A
      injections into the bladder wall provide a significant symptomatic and urodynamic
      improvement in children with neurogenic detrusor overactivity due to
      myelomeningocele who are on intermittent catheterization. The treatment seems to
      be safe and very well tolerated.

PMID- 24741420
TI  - Infant robotic bilateral upper urinary tract surgery.
AB  - We describe a case of robot-assisted laparoscopic bilateral upper urinary tract
      surgery in a 4-month-old infant for complex bilateral upper urinary tract
      duplication anomalies. 

PMID- 24741421
TI  - Testicular adrenal rest tumor in 11-Beta-hydroxylase deficiency driven congenital
      adrenal hyperplasia.
AB  - Testicular adrenal rest tumors (TART) occur often as asymptomatic nodules in
      corticotropin-dependent lesions aberrant adrenal tissue in congenital adrenal
      hyperplasia (CAH) patients. The present manuscript is about an unusual case of a
      16-year-old CAH patient due to 11beta-hydroxylase deficiency. He underwent
      testicle biopsy because of testicle tumor suspicion and diagnosed with TART. 

PMID- 24741422
TI  - Facial fracture management in northwest Nigeria.
AB  - BACKGROUND: Facial fracture is gradually become a public health problem in our
      community due to the attendant morbidity and mortality. Hence, the aim of this
      study was to determine the pattern of facial fracture in Dental and Maxillofacial
      Surgery Department of Usmanu Danfodiyo University Teaching Hospital. This cross
      sectional study was undertaken to provide information regarding gender, age,
      etiology, and diagnosis of patients with maxillofacial fractures. MATERIALS AND
      METHODS: A 1-year review of patients diagnosed and treated for facial fractures
      in Usmanu Danfodiyo University Teaching Hospital between January 2011 and
      December 2011. The diagnosis was based on radiographic data and clinical
      examination. The main analysis outcome measures were etiology, age, gender, site,
      and treatment. Data were organized and presented by means of descriptive
      statistics and Pearson's Chi-square test. The level of significance adopted was
      5%. RESULTS: A total of 40 patients were treated in this period. Over 95% were
      male, 81% were caused by road traffic crash (RTC) and 86.4% were in the 21-30
      years group. Most patients (52%) had mandibular fractures, and the most common
      site was the body. Most patients with midfacial fractures had fractures of the
      zygomaticomaxillary region (36%), while fractures of the parasymphyseal region
      were more common in the mandible 156 (31%). The most common treatment for jaw
      fractures was mandibulomaxillary fixation (MMF). Stable zygomatic complex
      fractures were reduced (elevated) intraorally, and unstable ones were supported
      by antral packs. CONCLUSIONS: This study highlights facial fractures secondary to
      RTC as a serious public health problem in our environment. Preventive strategies
      remain the cheapest way to reduce direct and indirect costs of the sequelae of
      RTC. It also bring to the fore the necessity to shift to open reduction and
      internal fixation (ORIF) of fractures.

PMID- 24741423
TI  - Pseudocyst of pinna and its treatment with surgical deroofing: an experience at
      tertiary hospitals.
AB  - INTRODUCTION: Pseudocyst of pinna is an uncommon condition hardly encountered in
      routine ENT practice. The involvement is usually seen in scaphoid, triangular
      fossa, and antihelix. Medical treatment is ineffective. Various treatments are
      suggested in the literature. The aims of the paper were to study the clinical
      characteristic of patients with pseudocysts and to share our experience with
      surgical deroofing and buttoning as a definitive treatment. MATERIALS AND
      METHODS: Twenty-six patients were diagnosed with pseudocyst of the auricle
      between April 2011 and 2013 in two medical college hospitals. Clinical
      characteristics were noted. All patients underwent incision and drainage with
      removal of anterior cartilage leaflet followed by buttoning for 12 days. RESULTS
      AND OBSERVATIONS: Out of 26 patients, only two were females. Involvement of left
      side was seen more than right one. None had bilateral involvement. Adults in the
      age group of 31-40 were commonly affected. Most common site of involvement was
      scaphoid and triangular fossa. The success rate with primary I and D and
      buttoning was 96%. CONCLUSIONS: Pseudocyst of the pinna is a benign condition of
      unknown etiology affecting the pinna, commonly encountered in middle-aged men.
      Many modalities of treatment have been recommended in the literature with varied
      recurrence and failure rates. The best form of treatment with minimum recurrence
      is incision and drainage with removal of anterior cartilage leaflet with
      buttoning.

PMID- 24741424
TI  - Loss of guide wire: a lesson learnt review of literature.
AB  - Catheterization of central veins is a routine technique which is widely used in
      emergency department and medical intensive care units. Seldinger's technique is
      widely used to place central venous and arterial catheters and is generally
      considered safe. The technique does have multiple potential risks. Guide wire
      related complications are rare but potentially serious. We describe a case of a
      lost guide wire during central venous catheter (CVC) insertion followed by a
      review of the literature of this topic. Measures which can be taken to prevent
      such complications are explained in detail as well as recommended steps to remedy
      errors should they occur. 

PMID- 24741425
TI  - Isolated pancreatic metastasis from malignant melanoma: is pancreatectomy
      worthwile?
AB  - Isolated pancreatic metastasis from malignant melanoma (IPMMM) is rare because
      most melanoma patients already have a widespread disease at diagnosis. No
      adjuvant systemic treatment is known to be efficient in this setting. Experience
      with pancreatic resection for IPMMM is limited and controversial. We report here
      the case of an IPMMM patient successfully treated by pancreaticoduodenectomy with
      a prolonged survival of 6 years. 

PMID- 24741426
TI  - Dentigerous cyst associated with ectopic canine and a supernumerary tooth: a rare
      occurrence.
AB  - Amongst the cysts of the jaw dentigerous cyst (DC) is one of the most prevalent
      types of odontogenic cysts, which is associated with the crown of an unerupted or
      developing tooth. DC is more commonly seen with mandibular third molar and
      maxillary canine and rarely other teeth are involved. These cysts seldom
      associate with supernumerary teeth. The purpose of this article is to describe a
      case of large dentigerous cyst associated with supernumerary teeth and an ectopic
      canine, which is a rare presentation along with its management. 

PMID- 24741427
TI  - Congenital uterovaginal prolapse present at birth.
AB  - Uterovaginal prolapse presenting at birth is very rare. The cause is attributed
      to conditions that can cause poor innervation or weakness of the pelvic floor
      muscle and the supporting ligaments. Different methods of treatment have been
      used in the past to reduce and maintain reduction of the prolapse. We report a
      case of a congenital UVP in a day old child noticed at delivery. He was delivered
      breech and had a sacral dimple with a tuft of hair. He was successfully managed
      conservatively with digital reduction and strapping of the buttocks down to the
      legs with crepe bandage for 72 h. 

PMID- 24741428
TI  - Glomus tumor of thumb occurring at unusual location.
AB  - Glomus tumour are painful swelling arising from glomus bodies. They are very rare
      in occurrence. Most of the time the presenting symptoms is severely painful
      fingertip without palpable swelling. Their most common location is the subungual
      region of digits. We report the rare case of a glomus tumour located in an
      uncommon location, i.e., at the tip of right thumb medial aspect near to tendon
      attachment. The peculiarity of this lesion is that this lesion on magnetic
      resonance imaging was found to arise from the insertion of flexure pollicis
      longus tendon and was reported as synovial swelling arising from tendon sheath.
      Clinical findings were consistent with glomus tumour. Excision biopsy confirmed
      diagnosis of glomus tumour. Although rare, glomus tumour should be considered as
      differential diagnosis for fingertip pain and excision of lesion gives complete
      pain relief. 

PMID- 24741429
TI  - Total Reconstruction of Lower Eyelid in a Post-traumatic Patient Using Modified
      Fricke's Cheek Flap.
AB  - Eyelids are very complex structure, reconstruction of which is a challenge to
      surgeons. Reconstruction of eyelids may be required in a variety of conditions
      like congenital anomalies, trauma, or postsurgical excision in malignant lesions
      involving the eyelids. There are numerous ways to reconstruct the eyelids; the
      best procedure depends on both the skill of the surgeon and the condition of the
      patient. Fricke' lateral temporal based flap was first described in 1829 for
      reconstruction of the eyelids and lateral canthal region. This flap had inherent
      problems regarding cosmetic appearance of the eyebrows. The modified Fricke's
      flap based on the cheek has the advantage of avoiding such complications. It is
      very easy and rapid outpatient department (OPD) based procedure with acceptable
      cosmetic and functional result. It can be done by all ear, nose, and throat (ENT)
      and head and neck surgeons without any reconstructive training. In this article
      we are presenting a case of total reconstruction of lower eyelid using the
      modified Fricke's cheek flap. 

PMID- 24741430
TI  - Successful laparoscopic removal of an ingested toothbrush.
AB  - Most ingested foreign bodies will pass through the gastrointestinal tract without
      any problems. On the other hand long, slender objects such as a toothbrush will
      rarely be able to negotiate the angulated and fixed retroperitoneal duodenal
      loop. Spontaneous toothbrush passage has never been described and therefore
      endoscopic or surgical removal is always required. Here we describe an
      asymptomatic young female presenting to out-patient clinic with a history of
      unintentional toothbrush ingestion 4 years prior. Endoscopic removal was
      unsuccessful because the toothbrush was partially embedded in to the gastric
      mucosa. We describe the second case to date of laparoscopic removal of a
      toothbrush via a gastrotomy with subsequent intra-corporeal repair of the defect.

PMID- 24741431
TI  - Axial Torsion of Gangrenous Meckel's Diverticulum Causing Small Bowel
      Obstruction.
AB  - Meckel's diverticulum (MD) is a commonly encountered congenital anomaly of the
      small intestine. We report an extremely unusual case of an axially torted,
      gangrenous MD presenting as acute intestinal obstruction. A 26-year-old male
      patient presented to our emergency department with 3 days history of abdominal
      pain, distention and bilious vomiting. On laparotomy, there was minimal
      hemorrhagic fluid localized in right iliac fossa and small bowel loops were
      dilated. A MD was seen attached to the mesentery of nonadjacent small bowel by a
      peritoneal band. The diverticulum was axially torted and gangrenous. In addition,
      there was compression of ileum by the peritoneal band resulting in intestinal
      obstruction, which was relieved on dividing the band. Resection and anastomosis
      of the small bowel including the MD was performed. We hereby report a rare and
      unusual complication of a MD. Although treatment outcome is generally good, pre
      operative diagnosis is often difficult. 

PMID- 24741432
TI  - Clinicoradiological diagnosis of cough-induced intercostal hernia.
AB  - Cough-induced intercostal hernias without any type of external trauma are very
      uncommon. There have been less than 10 cases documented in literature. This
      clinical report describes a 66-year-old male who developed an intercostal hernia
      induced by a severe cough due to bilateral pneumonia and a subsequent rib
      fracture. It took almost a full year to diagnose this patient's chest wall mass.
      Only after taking careful history and reviewing all the images, the diagnosis of
      intercostal hernia was made. He was referred to a cardiothoracic surgeon for
      treatment. Intercostal hernias can be caused by the sheer exertion of coughing
      without any prior history of trauma to the chest wall or abdomen. Early diagnosis
      is difficult and had to be based on clinical signs and symptoms. The imaging
      studies might help to establish diagnosis, but cannot replace a diligent
      examination and clinical interview. The treatment of the chest wall defect is
      case dependent. Surgical repair reinforcement of the intercostal muscles might be
      required with prosthetic nonabsorbable (polypropylene) mesh. 

PMID- 24741433
TI  - The twin amplatz sheath method: a modified technique of percutaneous
      cystolithotripsy for large bladder stones in female patients.
AB  - To minimize the operative time and to avoid open cystolithotomy in women with
      large bladder stone (>5 cm), we present here a modification of percutaneous
      cystolithotomy, a well-described standard procedure for urinary bladder stones.
      With this technique, suprapubic percutaneous access was achieved under
      cystoscopic guidance. The suprapubic tract was dilated and an Amplatz sheath of
      30 Fr was placed. Simultaneously, the urethra was sequentially dilated with
      fascial dilators and a 28 Fr Amplatz sheath was guided into the bladder and the
      foot end of the table lowered to 20 degrees  to facilitate high-speed outflow of
      irrigant and stone particles. A 26.5 Fr nephroscope was passed through the
      suprapubic Amplatz sheath and the stone was fragmented by intracorporeal
      pneumatic device keeping the stone close to the proximal end of the urethral
      Amplatz. These maneuvers help in washing out stone fragments periurethrally and
      keeping the endoscopic vision clear while breaking the stone. 

PMID- 24741434
TI  - Twin amplatz sheath method: a modified technique of percutaneous cystolithotripsy
      for large bladder stone in females.

PMID- 24741435
TI  - Anastomotic urethroplasty in female urethral stricture guided by cystoscopy - a
      point of technique.
AB  - PURPOSE: During anastomotic urethroplasty for stricture urethra with false
      passage using standard technique, there remains a chance of anastomosis of normal
      distal urethra to proximal false lumen. Herein, we present a point of technique
      in which by using antegrade cystoscope, one cannot just identify and dissect
      normal anatomical proximal urethral lumen, but also perform some of the steps for
      anastomosis under direct vision. This will avoid making anastomosis to false
      lumen and thus leading to further complications. MATERIALS AND METHODS: We report
      a case of 35-years-female who was presented to us with total mid-urethral
      stricture with false passage following multiple urethral dilatation attempts. We
      used antegrade cystoscopy during anastomotic urethroplasty to identify and
      dissect the proximal end of urethra thereby avoiding anastomosis to false tract.
      RESULTS: We successfully performed anastomotic urethroplasty avoiding false
      passage. Post-operative Uroflow showed Q max of 18 ml/sec. Voiding
      cystourethrogram post-operatively showed anastomosis between normal anatomical
      lumens. CONCLUSION: This modification of using antegrade cystoscopy helps to
      identify proximal urethral end which in turn helps in avoiding anastomosis to
      false tract and ensures anastomosis between normal lumens.

PMID- 24741436
TI  - A novel approach to the site-selective dual labelling of a protein via
      chemoselective cysteine modification.
AB  - Local protein microenvironment is used to control the outcome of reaction between
      cysteine residues and 2,5-dibromohexanediamide. The differential reactivity is
      exploited to introduce two orthogonal reactive handles onto the surface of a
      double cysteine mutant of superfolder green fluorescent protein in a
      regioselective manner. Subsequent elaboration with commonly used thiol and alkyne
      containing reagents affects site-selective protein dual labelling.

PMID- 24741437
TI  - The beauty of being (label)-free: sample preparation methods for SWATH-MS and
      next-generation targeted proteomics.
AB  - The combination of qualitative analysis with label-free quantification has
      greatly facilitated the throughput and flexibility of novel proteomic techniques.
      However, such methods rely heavily on robust and reproducible sample preparation
      procedures. Here, we benchmark a selection of in gel, on filter, and in solution
      digestion workflows for their application in label-free proteomics. Each
      procedure was associated with differing advantages and disadvantages. The in gel
      methods interrogated were cost effective, but were limited in throughput and
      digest efficiency. Filter-aided sample preparations facilitated reasonable
      processing times and yielded a balanced representation of membrane proteins, but
      led to a high signal variation in quantification experiments. Two in solution
      digest protocols, however, gave optimal performance for label-free proteomics. A
      protocol based on the detergent RapiGest led to the highest number of detected
      proteins at second-best signal stability, while a protocol based on acetonitrile
      digestion, RapidACN, scored best in throughput and signal stability but came
      second in protein identification. In addition, we compared label-free data
      dependent (DDA) and data independent (SWATH) acquisition. While largely similar
      in protein detection, SWATH outperformed DDA in quantification, reducing signal
      variation and markedly increasing the number of precisely quantified peptides. 

PMID- 24741438
TI  - Validation of predicted mRNA splicing mutations using high-throughput
      transcriptome data.
AB  - Interpretation of variants present in complete genomes or exomes reveals numerous
      sequence changes, only a fraction of which are likely to be pathogenic. Mutations
      have been traditionally inferred from allele frequencies and inheritance patterns
      in such data. Variants predicted to alter mRNA splicing can be validated by
      manual inspection of transcriptome sequencing data, however this approach is
      intractable for large datasets. These abnormal mRNA splicing patterns are
      characterized by reads demonstrating either exon skipping, cryptic splice site
      use, and high levels of intron inclusion, or combinations of these properties. We
      present, Veridical, an in silico method for the automatic validation of DNA
      sequencing variants that alter mRNA splicing. Veridical performs statistically
      valid comparisons of the normalized read counts of abnormal RNA species in mutant
      versus non-mutant tissues. This leverages large numbers of control samples to
      corroborate the consequences of predicted splicing variants in complete genomes
      and exomes. 

PMID- 24741439
TI  - Fiberoptic monitoring of central venous oxygen saturation (PediaSat) in small
      children undergoing cardiac surgery: continuous is not continuous.
AB  - BACKGROUND: Monitoring of superior vena cava saturation (ScvO 2) has become
      routine in the management of pediatric patients undergoing cardiac surgery. The
      objective of our study was to evaluate the correlation between continuous ScvO 2
      by the application of a fiber-optic oximetry catheter (PediaSat) and intermittent
      ScvO 2 by using standard blood gas measurements. These results were compared to
      those obtained by cerebral near infrared spectroscopy (cNIRS). SETTING: Tertiary
      pediatric cardiac intensive care unit (PCICU). METHODS AND MAIN RESULTS: A
      retrospective study was conducted in consecutive patients who were monitored with
      a 4.5 or 5.5 F PediaSat catheter into the right internal jugular vein. An in vivo
      calibration was performed once the patient was transferred to the PCICU and re
      calibration took place every 24 hours thereafter. Each patient had a NIRS placed
      on the forehead. Saturations were collected every 4 hours until extubation. Ten
      patients with a median age of 2.2 (0.13-8.5) years and a weight of 12.4 (3.9-24)
      kg were enrolled. Median sampling time was 32 (19-44) hours: 64 pairs of PediaSat
      and ScVO2 saturations showed a poor correlation (r=0.62, 95% CI 44-75; p<0.0001)
      and an average difference of -0.38 with a standard deviation of 13 and 95% limits
      of agreement from -26 to 25. Thirty-six pairs of cNIRS and ScVO2 saturations
      showed a fair correlation (r=0.79, 95% CI 0.60-0.89; p<0.0001) an average
      difference of -1.3 with a standard deviation of 7 and 95% limits of agreement
      from -15 to 12. Analysis of median percentage differences between PediaSat and
      ScvO2 saturation over time revealed that, although not statistically significant,
      the change in percentage saturation differences was clinically relevant after the
      8th hour from calibration (from -100 to +100%). CONCLUSION: PediaSat catheters
      showed unreliable performance in our cohort. It should be further investigated
      whether repeating calibrations every 8 hours may improve the accuracy of this
      system. CNIRS may provide similar results with a lower invasiveness.

PMID- 24741440
TI  - FeatureViewer, a BioJS component for visualization of position-based annotations
      in protein sequences.
AB  - SUMMARY: FeatureViewer is a BioJS component that lays out, maps, orients, and
      renders position-based annotations for protein sequences. This component is
      highly flexible and customizable, allowing the presentation of annotations by
      rows, all centered, or distributed in non-overlapping tracks. It uses either
      lines or shapes for sites and rectangles for regions. The result is a powerful
      visualization tool that can be easily integrated into web applications as well as
      documents as it provides an export-to-image functionality. AVAILABILITY:
      https://github.com/biojs/biojs/blob/master/src/main/javascript/Biojs.FeatureViewe
      .js; http://dx.doi.org/10.5281/zenodo.7719.

PMID- 24741441
TI  - An image-based, dual fluorescence reporter assay to evaluate the efficacy of
      shRNA for gene silencing at the single-cell level.
AB  - RNA interference (RNAi) is widely used to suppress gene expression in a specific
      manner. The efficacy of RNAi is mainly dependent on the sequence of small
      interfering RNA (siRNA) in relation to the target mRNA. Although several
      algorithms have been developed for the design of siRNA, it is still difficult to
      choose a really effective siRNA from among multiple candidates. In this article,
      we report the development of an image-based, quantitative, ratiometric
      fluorescence reporter assay to evaluate the efficacy of RNAi at the single-cell
      level. Two fluorescence reporter constructs are used. One expresses the candidate
      small hairpin RNA (shRNA) together with an enhanced green fluorescent protein
      (EGFP); the other expresses a 19-nt target sequence inserted into a cassette
      expressing a red fluorescent protein (either DsRed or mCherry). Effectiveness of
      the candidate shRNA is evaluated as the extent to which it knocks down expression
      of the red fluorescent protein. Thus, the red-to-green fluorescence intensity
      ratio (appropriately normalized to controls) is used as the read-out for
      quantifying the siRNA efficacy at the individual cell level. We tested this dual
      fluorescence assay and compared predictions to actual endogenous knockdown levels
      for three different genes (vimentin, lamin A/C and Arp3) and twenty different
      shRNAs. For each of the genes, our assay successfully predicted the target
      sequences for effective RNAi. To further facilitate testing of RNAi efficacy, we
      developed a negative selection marker ( ccdB) method for construction of shRNA
      and red fluorescent reporter plasmids that allowed us to purify these plasmids
      directly from transformed bacteria without the need for colony selection and DNA
      sequencing verification. 

PMID- 24741442
TI  - Advancing the activity cliff concept, part II.
AB  - We present a follow up contribution to further complement a previous commentary
      on the activity cliff concept and recent advances in activity cliff research.
      Activity cliffs have originally been defined as pairs of structurally similar
      compounds that display a large difference in potency against a given target. For
      medicinal chemistry, activity cliffs are of high interest because structure
      activity relationship (SAR) determinants can often be deduced from them. Herein,
      we present up-to-date results of systematic analyses of the ligand efficiency and
      lipophilic efficiency relationships between activity cliff-forming compounds,
      which further increase their attractiveness for the practice of medicinal
      chemistry. In addition, we summarize the results of a new analysis of coordinated
      activity cliffs and clusters they form. Taken together, these findings
      considerably add to our evaluation and current understanding of the activity
      cliff concept. The results should be viewed in light of the previous commentary
      article. 

PMID- 24741443
TI  - Coexistence of Ankylosing Spondylitis and Lofgren's Syndrome.
AB  - A 46-year-old male patient diagnosed with ankylosing spondylitis presented to our
      polyclinic with complaints of pain, swelling, and limitation in joint mobility in
      both ankles and erythema nodosum skin lesions in both pretibial sites. The
      sacroiliac joint graphy and the MRI taken revealed active and chronic
      sacroiliitis. On the thorax CT, multiple mediastinal and hilar lymphadenopathies
      were reported. Mediastinoscopic excisional lymph node biopsy was taken and
      noncalcified granulomatous structures, lymphocytes, and histiocytes were
      determined on histopathological examination. The patients were diagnosed with
      ankylosing spondylitis, sarcoidosis, and Lofgren's syndrome. NSAIDs,
      sulfasalazine, and low dose corticosteroid were started. Significant regression
      was seen in the patient's subjective and laboratory assessments. 

PMID- 24741444
TI  - Postcardiotomy mechanical circulatory support in two infants with williams'
      syndrome.
AB  - Supravalvar aortic stenosis (SVAS) in patients with Williams' syndrome is often
      accompanied by coronary, pulmonary, and even myocardial lesions and therefore
      associated with increased perioperative morbidity and mortality. Extracorporeal
      membrane oxygenation (ECMO) provides reliable short-term mechanical circulatory
      support to patients, especially young, in acute postoperative cardiac failure
      when conventional means are ineffective. The incorporation of centrifugal pumps
      in these systems has made their use more efficient and less traumatic. We
      describe our experience of using the Levitronix CentriMag pump in two patients
      with Williams' syndrome who underwent surgical correction of supravalvular aortic
      stenosis. 

PMID- 24741445
TI  - Human interferon alpha-2b: a therapeutic protein for cancer treatment.
AB  - Human interferon alpha (hIFNalpha) is a wide biological activity cytokine that is
      used in hepatitis and cancer treatments. It regulates many genes that are
      involved in antiviral and antiproliferative activities. This mini review focuses
      on human interferon alpha-2b (hIFNalpha-2b) as therapeutic protein for cancer
      treatment. The review covers hIFNalpha-2b molecular characteristic and its
      molecular mechanism by Janus activated kinase/signal transducer activation of
      transcription (JAK-STAT) pathway. The JAK-STAT pathway regulates not only
      proteins involved in inhibition of proliferation but also apoptosis. As
      additional discussion of clinical applications, the use of recombinant hIFNalpha
      2b (rhIFNalpha-2b) as therapeutic protein in several types of cancer is also
      explained. 

PMID- 24741446
TI  - Assessment of technetium-99m labeled macroaggregated albumin rhinoscintigraphy
      for the measurement of nasal mucociliary transport rate: intratest,
      interobserver, and intraobserver reproducibility.
AB  - Objectives. The measurement of mucociliary transport velocity by
      rhinoscintigraphy with Tc-99m-macroaggregated albumin ((99m)Tc-MAA) is reliable
      measure of mucociliary clearance. The aim of this study is to assess the
      intratest, interobserver, and intraobserver reproducibility of nasal mucociliary
      transport rate (NMTR) measurement. Materials and Methods. Twenty-two subjects
      were evaluated to determine intratest reproducibility and a group of 35 subjects
      was examined to determine inter- and intraobserver reproducibility.
      Rhinoscintigraphy with (99m)Tc-MAA was used to measure NMTR in all study
      subjects. Paired NMTR measurements were compared using a range of statistical
      methodologies. Intraclass correlation coefficients (ICC) and repeatability
      coefficients and Bland-Altman plots were applied to assess the degree of
      intratest, interobserver, and intraobserver variation. Results. Statistical
      analysis of test and retest experiments demonstrated the statistical equivalence
      of intratest NMTR measurements, interobserver NMTR measurements, and
      intraobserver NMTR measurements. The intratest ICC, interobserver ICC, and
      intraobserver ICC were 0.96, 0.83, and 0.91, respectively, indicating that
      intratest and intraobserver reproducibility are excellent and interobserver
      reproducibility is good. Conclusions. Rhinoscintigraphy using (99m)Tc-MAA results
      in highly reproducible measurement of NMTR. The use of radionuclide imaging in
      measuring NMTR results in excellent intratest and intraobserver reproducibility
      and good interobserver reliability. 

PMID- 24741447
TI  - Ectopic fat assessment focusing on cardiometabolic and renal risk.
AB  - It is well known that people with high levels of body fat are at higher risk for
      developing diabetes mellitus, kidney disease, and cardiovascular disorders. Since
      individuals who are slightly overweight, or even individuals of normal weight,
      can vary in body fat distribution, their metabolic profiles and the degree of
      association of these profiles with cardiometabolic risk factors may differ. Fat
      distribution might be more of a predictive factor for cardiorenometabolic risk
      than obesity itself, which has led researchers to investigate whether ectopic fat
      accumulation may partially account for the development of cardiorenometabolic
      disorders. In addition to visceral obesity, fat can accumulate in the liver and
      muscle, and these intrahepatic and intramuscular lipid stores are associated with
      insulin resistance and adverse metabolic phenotypes. More recently, pericardial
      fat, perivascular fat, and perirenal fat were found to be associated with
      coronary atherosclerosis, cardiovascular diseases, and kidney damage,
      respectively. Thus, regional fat distribution may play a key role in
      understanding the development of cardiorenometabolic diseases in nonobese people.

PMID- 24741448
TI  - Differential diagnosis of adrenal mass using imaging modality: special emphasis
      on f-18 fluoro-2-deoxy-d-glucose positron emission tomography/computed
      tomography.
AB  - Adrenal incidentalomas are adrenal masses serendipitously detected during an
      imaging study performed for reasons unrelated to suspicion of adrenal disease.
      The incidence of adrenal incidentalomas has increased because of the widespread
      use of various imaging modalities. In oncology patients with adrenal
      incidentalomas, the characterization of the adrenal masses is challenging because
      nearly 50% of incidental adrenal masses are metastatic lesions that need special
      medical attention. Although unenhanced computed tomography (CT) densitometry,
      chemical shift magnetic resonance imaging (MRI), delayed contrast-enhanced CT and
      CT histogram analysis have been used as sensitive and specific modalities for
      differentiating benign from malignant adrenal masses, F-18 fluoro-2-deoxy-D
      glucose positron emission tomography (F-18 FDG PET)/CT is a highly accurate
      imaging modality compared to CT or MRI, especially when these two imaging
      modalities are combined. In addition, a semiquantitative analysis using
      standardized uptake value ratio further improves the diagnostic accuracy of F-18
      FDG PET/CT in differentiating benign from malignant adrenal masses. Thus, F-18
      FDG PET/CT is very helpful for determining the best therapeutic management,
      especially for assessing the need for surgery. 

PMID- 24741449
TI  - Sweet Taste-Sensing Receptors Expressed in Pancreatic beta-Cells: Sweet Molecules
      Act as Biased Agonists.
AB  - The sweet taste receptors present in the taste buds are heterodimers comprised of
      T1R2 and T1R3. This receptor is also expressed in pancreatic beta-cells. When the
      expression of receptor subunits is determined in beta-cells by quantitative
      reverse transcription polymerase chain reaction, the mRNA expression level of
      T1R2 is extremely low compared to that of T1R3. In fact, the expression of T1R2
      is undetectable at the protein level. Furthermore, knockdown of T1R2 does not
      affect the effect of sweet molecules, whereas knockdown of T1R3 markedly
      attenuates the effect of sweet molecules. Consequently, a homodimer of T1R3
      functions as a receptor sensing sweet molecules in beta-cells, which we designate
      as sweet taste-sensing receptors (STSRs). Various sweet molecules activate STSR
      in beta-cells and augment insulin secretion. With regard to intracellular
      signals, sweet molecules act on STSRs and increase cytoplasmic Ca(2+) and/or
      cyclic AMP (cAMP). Specifically, when an STSR is stimulated by one of four
      different sweet molecules (sucralose, acesulfame potassium, sodium saccharin, or
      glycyrrhizin), distinct signaling pathways are activated. Patterns of changes in
      cytoplasmic Ca(2+) and/or cAMP induced by these sweet molecules are all different
      from each other. Hence, sweet molecules activate STSRs by acting as biased
      agonists. 

PMID- 24741450
TI  - Prevalence and risk factors of subclinical thyroid disease.
AB  - Subclinical thyroid disease is defined biochemically by an abnormal thyrotropin
      (TSH) level and normal serum-free thyroxine level. The prevalence of this
      condition varies according to the reference range for TSH and geographic or
      demographic factors. Recently, several studies, including our community-based
      cohort studies, have reported on the incidence of subclinical thyroid disease in
      Korea. Using these studies, we reviewed the prevalence and risk factors of
      subclinical thyroid disease, focusing on subclinical hypothyroidism. 

PMID- 24741451
TI  - Testosterone replacement therapy and bone mineral density in men with
      hypogonadism.

PMID- 24741452
TI  - Diagnostic Whole-Body Scan May Not Be Necessary for Intermediate-Risk Patients
      with Differentiated Thyroid Cancer after Low-Dose (30 mCi) Radioactive Iodide
      Ablation.
AB  - BACKGROUND: A diagnostic whole-body scan (WBS) is recommended 6 to 12 months
      after total thyroidectomy and radioactive iodide ablation in intermediate- or
      high-risk patients with differentiated thyroid cancer (DTC). The aim of this
      study was to evaluate the necessity of a diagnostic WBS after radioactive iodide
      ablation in intermediate-risk patients with DTC. METHODS: A total of 438 subjects
      were included in the study: 183 low-risk subjects and 255 intermediate-risk
      subjects according to the American Thyroid Association guideline. All subjects
      diagnosed with DTC received 1,100 MBq (30 mCi) activity of radioiodine (I-131)
      following total thyroidectomy. On follow-up, all subjects underwent a diagnostic
      I-131 WBS after thyroid hormone withdrawal. RESULTS: After initial radioactive
      iodide ablation, 95.1% of low-risk patients and 91.4% of intermediate-risk
      patients showed no uptake on diagnostic WBS (P=0.135). Intermediate-risk patients
      with stimulated thyroglobulin (Tg) levels higher than 2.0 ng/mL showed a greater
      rate of radioactive iodine uptake on diagnostic WBS. Four intermediate-risk
      patients showed recurrence during the 16 to 80 months follow-up period. Three of
      the four patients with recurrence showed no uptake on diagnostic WBS and had a
      stimulated Tg level less than 2.0 ng/mL. CONCLUSION: A diagnostic I-131 WBS after
      radioactive iodide ablation in intermediate-risk patients with DTC may not be
      necessary. A large prospective study is necessary to determine the necessity of
      diagnostic WBS in intermediate-risk patients with DTC.

PMID- 24741453
TI  - Correlation between Expression of Glucose Transporters in Granulosa Cells and
      Oocyte Quality in Women with Polycystic Ovary Syndrome.
AB  - BACKGROUND: The glucose transporters (GLUTs) exhibit different tissue-specific
      expression. This study aimed to investigate the types of GLUTs expressed in human
      granulosa cells (GCs) obtained from women with polycystic ovary syndrome (PCOS)
      and their relationship with insulin resistance (IR) and the outcomes of in vitro
      maturation (IVM) of immature oocytes. METHODS: Expression of GLUTs was evaluated
      in GCs from women with PCOS with or without IR. Thirty-six women with PCOS
      undergoing an IVM program were included. Differential gene expression between the
      insulin sensitive (IS) and IR group was measured by reverse transcription
      polymerase chain reaction. RESULTS: Expression of GLUTs 1, 3, 5, 8, and 13 was
      constitutive, whereas expression of GLUTs 2 and 7 was not observed in human GCs.
      The remaining GLUTs, 4, 6, 9, 10, 11, and 12, were differentially expressed among
      patients according to metabolic status, such as insulin sensitivity. A higher
      number of GCs from patients with IR (92%) expressed GLUT6 than GCs from IS PCOS
      patients (46.3%). Logistic regression showed that expression of GLUTs 9, 11, and
      12 correlates with rates of IVM at 48 hours, fertilization, and implantation,
      respectively. CONCLUSION: This is the first report describing the expression
      pattern of all 13 members of the GLUT family in human GCs. Results of the present
      study suggest that patients' insulin sensitivity regulates GLUT expression in GCs
      in PCOS patients, and this may control oocyte quality for IVM and subsequent
      processes such as fertilization and implantation in patients taking part in an in
      vitro fertilization program.

PMID- 24741454
TI  - Testosterone replacement and bone mineral density in male pituitary tumor
      patients.
AB  - BACKGROUND: Hypopituitarism is associated with osteoporosis and osteopenia
      especially when hypogonadotropic hypogonadism is present. Despite hypopituitarism
      being an important cause of secondary osteoporosis, osteoporosis in patients
      receiving surgery for pituitary tumors in Korea has not been studied. In this
      study, we evaluated the effects of testosterone replacement therapy (TRT) on bone
      mineral density (BMD) in postoperative hypogonadal patients with pituitary
      tumors. METHODS: To examine the effect of TRT on BMD, we performed a
      retrospective observational study in 21 postoperative male patients who underwent
      pituitary tumor surgery between 2003 and 2012 at the Ajou University Hospital.
      Testosterone was replaced in postoperative hypogonadal patients by regular
      intramuscular injection, daily oral medication, or application of transdermal
      gel. BMD (g/cm(2)) measurements of central skeletal sites (lumbar spine, femoral
      neck, and total femur) were obtained using dual-energy X-ray absorptiometry (GE
      Lunar). For lumbar spine BMD, L1 to L4 values were chosen for analysis. Femur
      neck and total femur were also analyzed. RESULTS: During the follow-up period
      (mean, 56 months; range, 12 to 99 months) serum testosterone levels increased
      with the administration of TRT (P=0.007). There was significant improvement
      (4.56%+/-9.81%) in the lumbar spine BMD compared to baseline BMD. There were no
      significant changes in the femur neck BMD or total femur BMD. We did not find any
      statistically significant relationships between changes in testosterone levels
      and BMD using Spearman correlation analysis. CONCLUSION: Our results indicated
      that TRT used in the postoperative period for hypogonadal pituitary tumor surgery
      patients may have beneficial effects on the BMD of the spine.

PMID- 24741455
TI  - Curcumin Enhances Docetaxel-Induced Apoptosis of 8505C Anaplastic Thyroid
      Carcinoma Cells.
AB  - BACKGROUND: Anaplastic thyroid cancer (ATC) is one of the most aggressive
      malignancies in humans, and its progression is poorly controlled by existing
      therapeutic methods. Curcumin has been shown to suppress inflammation and
      angiogenesis. In this study, we evaluated whether curcumin could augment
      docetaxel-induced apoptosis of ATC cells. We also analyzed changes in nuclear
      factor kappaB (NF-kappaB) and cyclooxygenase-2 (COX-2) expression levels to
      delineate possible mechanisms of their combined action. METHODS: ATC cells were
      cultured and treated with curcumin and docetaxel alone or in combination. The
      effects on cell viability were determined by MTS assay. Apoptosis was assessed by
      annexin V staining and confirmed by flow cytometric analysis. Caspase, COX-2, NF
      kappaB levels were assayed by Western blotting. RESULTS: Curcumin combined with
      docetaxel led to lower cell viability than treatment with docetaxel or curcumin
      alone. Annexin V staining followed by flow cytometric analysis demonstrated that
      curcumin treatment enhanced the docetaxel-induced apoptosis of ATC cells.
      Additionally, curcumin inhibited docetaxel-induced p65 activation and COX-2
      expression. CONCLUSION: We conclude that curcumin may enhance docetaxel's
      antitumor activity in ATC cells by interfering with NF-kappaB and COX-2. Our
      results suggest that curcumin may emerge as an attractive therapeutic candidate
      to enhance the antitumor activity of taxanes in ATC treatment.

PMID- 24741456
TI  - Functional Role of Parkin against Oxidative Stress in Neural Cells.
AB  - BACKGROUND: Parkinson disease (PD) is caused by selective cell death of
      dopaminergic neurons in the substantia nigra. An early onset form of PD,
      autosomal recessive juvenile parkinsonism has been associated with a mutation in
      the parkin gene. The function of parkin is known to remove misfolding proteins
      and protect cell death. We aimed to investigate the role of parkin against
      oxidative stress in neuronal cells. METHODS: Parkin knockout embryonic stem cells
      (PKO ES cells) were differentiated into neurons by adherent monolayer culture
      method. Oxidative stress was induced by the treatment of 1-methyl-4
      phenylpyridinium (MPP(+)) in neurons derived from wild type and PKO ES cells, and
      cell viability was examined by MTT assay. After exposure to MPP(+), Tuj1-positive
      cell population was compared between PKO and wild type cells by fluorescence
      activated cell sorter (FACS) analysis. The activated caspase3 protein level was
      also measured by Western blot analysis, FACS and immunocytochemistry. RESULTS:
      There was no difference in the efficiency of neuronal differentiation between
      wild type and PKO ES cells. After exposure to MPP(+), no significant differences
      were found in cell viability and Tuj1-positive cell population between the two
      groups determined by MTT assay and FACS analysis, respectively. The activated
      caspase3 protein levels examined by Western blot analysis, FACS and
      immunocytochemistry were not changed in PKO cells compared with those of wild
      type cells after MPP(+) treatment. CONCLUSION: These results suggest that PKO
      neuronal cells including dopaminergic neurons are not sensitive to caspase3
      dependent cell death pathway during the response against MPP(+)-induced oxidative
      stress.

PMID- 24741457
TI  - Short-term caloric restriction does not reduce bone mineral density in rats with
      early type 2 diabetes.
AB  - BACKGROUND: The effect of caloric restriction (CR) in the setting of diabetes on
      bone metabolism has not yet been fully studied. The aim of this study is to
      determine if short-term CR alters bone mass and metabolism in Otsuka Long-Evans
      Tokushima fatty (OLETF) rats, an animal model of type 2 diabetes. METHODS: Four
      groups (n=5) were created: OLETF rats with food ad libitum (AL), OLETF rats with
      CR, Long-Evans Tokusima Otsuka (LETO) rats with food AL, and LETO rats with CR.
      The CR condition was imposed on 24-week-old male rats using a 40% calorie
      reduction for 4 weeks. The effect of CR on femoral bone mineral density (BMD) was
      assessed by dual-energy X-ray absorptiometry. Serum markers were measured by
      immunoassay. RESULTS: After 4 weeks of CR, body weight decreased in both strains.
      The BMD decreased in LETO rats and was maintained in OLETF rats. After adjustment
      for body weight, BMD remained lower in LETO rats (P=0.017) but not OLETF rats
      (P=0.410). Bone-specific alkaline phosphatase levels decreased in LETO rats
      (P=0.025) but not in OLEFT rats (P=0.347). Serum leptin levels were reduced after
      CR in both strains, but hyperleptinemia remained in OLETF rats (P=0.009). CR
      increased 25-hydroxyvitamin D levels in OLETF rats (P=0.009) but not in LETO rats
      (P=0.117). Additionally, interleukin-6 and tumor necrosis factor-alpha levels
      decreased only in OLETF rats (P=0.009). CONCLUSION: Short-term CR and related
      weight loss were associated with decreases of femoral BMD in LETO rats while BMD
      was maintained in OLETF rats. Short-term CR may not alter bone mass and
      metabolism in type 2 diabetic rats.

PMID- 24741458
TI  - Hyponatremia after thyroid hormone withdrawal in a patient with papillary thyroid
      carcinoma.
AB  - Hyponatremia is an electrolyte abnormality commonly found in clinical practice.
      It is important to diagnose the underlying etiology of the hyponatremia and
      correct it appropriately because severe hyponatremia can cause serious
      complications and substantially increase the risk of mortality. Although
      hypothyroidism is known to be a cause of hyponatremia, it is rare that
      hyponatremia occurs in relation to hypothyroidism induced by thyroid hormone
      withdrawal in patients with differentiated thyroid cancer. We report a case of a
      76-year-old woman with papillary thyroid carcinoma presenting with severe
      hyponatremia related to hypothyroidism induced by thyroid hormone withdrawal for
      radio-active iodine whole-body scanning, who was treated by thyroid hormone
      replacement and hydration. Considering that the incidence of differentiated
      thyroid cancer is rapidly increasing, physicians should be aware that, although
      uncommon, hyponatremia can occur in patients undergoing radioiodine therapy or
      diagnostic testing. 

PMID- 24741459
TI  - Pheochromocytoma with markedly abnormal liver function tests and severe
      leukocytosis.
AB  - Pheochromocytoma is a rare neuroendocrine tumor arising from the medulla of the
      adrenal glands, which causes an overproduction of catecholamines. The common
      symptoms are headache, palpitations, and sweating; however, various other
      clinical manifestations might also be present. Accurate diagnosis of
      pheochromocytoma is important because surgical treatment is usually successful,
      and associated clinical problems are reversible if treated early. A 49-year-old
      man with a history of uncontrolled hypertension and diabetes mellitus presented
      with chest pain, fever, and sweating. His liver function tests and white blood
      cell counts were markedly increased and his echocardiography results suggested
      stress-induced cardiomyopathy. His abdominal computed tomography showed a 5*5-cm
      sized tumor in the left adrenal gland, and laboratory tests confirmed
      catecholamine overproduction. After surgical resection of the left adrenal gland,
      his liver function tests and white blood cell counts normalized, and
      echocardiography showed normal cardiac function. Moreover, his previous
      antihypertensive regimen was deescalated, and his previously uncontrolled blood
      glucose levels normalized without medication. 

PMID- 24741460
TI  - Hypoparathyroidism and subclinical hypothyroidism with secondary hemochromatosis.
AB  - Hemochromatosis is an inherited genetic disorder of iron metabolism which can
      also occur as a secondary result of iron-overload. It leads to organ damage such
      as cardiomyopathy, liver cirrhosis, hypogonadism, and diabetes. This paper
      discusses a case of secondary hemochromatosis associated with repeated
      transfusions, presenting as asymptomatic hypoparathyroidism and subclinical
      hypothyroidism with multiple organ involvement. The 29-year-old female, who had
      severe aplastic anemia, received multiple transfusions totaling approximately
      1,400 units of red blood cells over 15 years. During her routine laboratory
      examination, hypocalcemia was detected with decreased intact parathyroid hormone
      and increased thyroid stimulating hormone. Serum ferritin, iron, and total iron
      binding capacity had increased to 27,583.03 ng/mL, 291 ug/dL, and 389 ug/dL,
      respectively. She had unusually bronze skin and computed tomography revealed iron
      deposition in the thyroid, liver, and heart. Multiorgan involvement as seen in
      this case is rare in hemochromatosis associated with secondary transfusions. To
      the best of the author's knowledge, this is the first case report in Korea of
      hypoparathyroidism and subclinical hypothyroidism due to iron deposition in the
      parathyroid and thyroid gland. 

PMID- 24741461
TI  - Medullary thyroid carcinoma with ectopic adrenocorticotropic hormone syndrome.
AB  - Ectopic adrenocorticotropic hormone (ACTH) syndrome is caused most frequently by
      a bronchial carcinoid tumor or by small cell lung cancer. Medullary thyroid
      carcinoma (MTC) is a rare etiology of ectopic ACTH syndrome. We describe a case
      of Cushing syndrome due to ectopic ACTH production from MTC in a 48-year-old
      male. He was diagnosed with MTC 14 years ago and underwent total thyroidectomy,
      cervical lymph node dissection and a series of metastasectomies. MTC was
      confirmed by the pathological examination of the thyroid and metastatic
      mediastinal lymph node tissues. Two years after his last surgery, he developed
      Cushingoid features, such as moon face and central obesity, accompanied by
      uncontrolled hypertension and new-onset diabetes. The laboratory results were
      compatible with ectopic ACTH syndrome. A bilateral adrenalectomy improved the
      clinical and laboratory findings that were associated with Cushing syndrome. This
      is the first confirmed case of ectopic ACTH syndrome caused by MTC in Korea. 

PMID- 24741462
TI  - Letter: Association between Cardiac Autonomic Neuropathy, Diabetic Retinopathy
      and Carotid Atherosclerosis in Patients with Type 2 Diabetes (Endocrinol Metab
      2013;28:309-19, Chan-Hee Jung et al.).

PMID- 24741463
TI  - Response: Association between Cardiac Autonomic Neuropathy, Diabetic Retinopathy
      and Carotid Atherosclerosis in Patients with Type 2 Diabetes (Endocrinol Metab
      2013;28:309-19, Chan-Hee Jung et al.).

PMID- 24741464
TI  - Intra-observer reproducibility of whole slide imaging for the primary diagnosis
      of breast needle biopsies.
AB  - BACKGROUND: Automated whole slide imaging (WSI), also known as virtual microscopy
      is rapidly becoming an important tool in diagnostic pathology. Currently, the
      primary utilization of the technique is for transmission of digital images, for
      second opinion consultation, as well as for quality assurance and education. The
      high-resolution of digital images along with the refinement of technology could
      now allow for WSI to be used as an alternative to conventional microscopy (CM) as
      a first line diagnostic platform. However, the accuracy and reproducibility of
      the technology for the routine histopathologic diagnosis has not been established
      yet. This study was undertaken to compare the intra-observer variability of WSI
      and CM in the primary diagnosis of breast biopsies. MATERIALS AND METHODS: One
      hundred and three consecutive core needle biopsies of breast were selected for
      this study. Each slide was digitally scanned and the images were stored in a
      shared file. Three board-certified pathologists independently reviewed the glass
      slides by CM first, and in an interval of 2-3 weeks for the 2(nd) time to
      establish their baseline CM versus CM reproducibility. They then reviewed the
      digital images of all cases following the same interval of time to compare the
      reproducibility of WSI versus CM for each observer. The diagnostic categories
      included the typical range of benign and malignant mammary lesions. RESULTS: The
      intra-observer variability for CM versus CM was 4%, 7%, and 0% for observers 1,
      2, and 3 respectively. The diagnostic variability for WSI versus CM was 1%, 4%,
      and 1% for the same observers. All diagnostic disagreements were between ductal
      hyperplasia and atypical ductal hyperplasia. There was no intra-observer
      disagreement in the diagnosis of benign versus malignant disease. CONCLUSIONS:
      The intra-observer variability in the diagnosis of the core needle biopsies of
      the breast by high-resolution, WSI was the same as conventional glass slide
      microscopy. These results suggest that, WSI could be used similar to CM for the
      initial diagnosis of breast biopsies.

PMID- 24741465
TI  - Utility of alert-based CDSS in CPOE to improve compliance with plasma transfusion
      guidelines.

PMID- 24741466
TI  - The laboratory information system functionality assessment tool: Ensuring optimal
      software support for your laboratory.

PMID- 24741467
TI  - Interleukin-30: A novel microenvironmental hallmark of prostate cancer
      progression.
AB  - Metastatic prostate cancer is a leading cause of cancer-related death in men
      worldwide. We have recently discovered that IL-30 shapes the microenvironment of
      prostate cancer and tumor-draining lymph nodes to favor tumor progression. IL-30
      supports tumor growth in vitro, and IL-30 expression in prostate cancer patients
      is associated with high tumor grade and metastatic stage of disease. Thus, IL-30
      may constitute a valuable target for modern therapeutic approaches to hamper
      prostate cancer progression.

PMID- 24741468
TI  - Comparison of Nonprecious Metal Cathode Materials for Methane Production by
      Electromethanogenesis.
AB  - In methanogenic microbial electrolysis cells (MMCs), CO2 is reduced to methane
      using a methanogenic biofilm on the cathode by either direct electron transfer or
      evolved hydrogen. To optimize methane generation, we examined several cathode
      materials: plain graphite blocks, graphite blocks coated with carbon black or
      carbon black containing metals (platinum, stainless steel or nickel) or insoluble
      minerals (ferrihydrite, magnetite, iron sulfide, or molybdenum disulfide), and
      carbon fiber brushes. Assuming a stoichiometric ratio of hydrogen
      (abiotic):methane (biotic) of 4:1, methane production with platinum could be
      explained solely by hydrogen production. For most other materials, however,
      abiotic hydrogen production rates were insufficient to explain methane
      production. At -600 mV, platinum on carbon black had the highest abiotic hydrogen
      gas formation rate (1600 +/- 200 nmol cm-3 d-1) and the highest biotic methane
      production rate (250 +/- 90 nmol cm-3 d-1). At -550 mV, plain graphite (76 nmol
      cm-3 d-1) performed similarly to platinum (73 nmol cm-3 d-1). Coulombic
      recoveries, based on the measured current and evolved gas, were initially greater
      than 100% for all materials except platinum, suggesting that cathodic corrosion
      also contributed to electromethanogenic gas production.

PMID- 24741469
TI  - Babassu nut residues: potential for bioenergy use in the North and Northeast of
      Brazil.
AB  - Babassu is considered the largest native oil resource worldwide and occurs
      naturally in Brazil. The purpose of this study was to evaluate the potential of
      babassu nut residues (epicarp, mesocarp and endocarp) for bioenergy use,
      especially for direct combustion and charcoal production. The material was
      collected in the rural area of the municipality of Sitio Novo do Tocantins, in
      the state of Tocantins, Brazil. Analyses were performed considering jointly the
      three layers that make up the babassu nut shell. The following chemical
      characterizations were performed: molecular (lignin, total extractives and
      holocellulose), elemental (C, H, N, S and O), immediate (fixed carbon, volatiles
      and ash), energy (higher heating value and lower heating value), physical (basic
      density and energy density) and thermal (thermogravimetry and differential
      thermal analysis), besides the morphological characterization by scanning
      electron microscopy. Babassu nut residues showed a high bioenergy potential,
      mainly due to their high energy density. The use of this biomass as a bioenergy
      source can be highly feasible, given their chemical and thermal characteristics,
      combined with a low ash content. Babassu nut shell showed a high basic density
      and a suitable lignin content for the sustainable production of bioenergy and
      charcoal, capable of replacing coke in Brazilian steel plants. 

PMID- 24741470
TI  - Clinical and prognostic factors associated with diagnostic wait times by breast
      cancer detection method.
AB  - INTRODUCTION: Although prognostic differences between screen-detected, interval
      and symptomatic breast cancers are known, factors associated with wait times to
      diagnosis among these three groups have not been studied. METHODS: Of the 16,373
      invasive breast cancers diagnosed between January 1, 1995 and December 31, 2003
      in a cohort of Ontario women aged 50 to 69, a random sample (N = 2,615) were
      selected for chart abstraction. Eligible women were classified according to
      detection method; screen-detected (n = 1181), interval (n = 319) or symptomatic
      (n = 406). Diagnostic wait time was calculated from the initial imaging or biopsy
      to breast cancer diagnosis. Logistic regression analysis examined associations
      between diagnostic wait times dichotomized as greater or less than the median and
      demographic, clinical and prognostic factors separately for each detection
      cohort. RESULTS: Women who underwent an open biopsy had significantly longer than
      median wait times to diagnosis, compared to women who underwent a fine needle
      aspiration or core biopsy; (screen-detected OR = 2.76, 95% CI = 2.14-3.56;
      interval OR = 2.56, 95% CI = 1.50-4.35; symptomatic OR = 5.56, 95% CI = 3.33
      9.30). Additionally, screen-detected breast cancers diagnosed with stage II and
      symptomatic cancers diagnosed at stage III or IV had significantly shorter
      diagnostic wait times compared to those diagnosed at stage 1 (OR = 0.66 95% CI =
      0.50-0.87 and OR = 0.46, 95% CI = 0.25-0.85 respectively). CONCLUSIONS: Our study
      is consistent with expedited diagnostic work-up for breast cancers with more
      advanced prognostic features. Furthermore, women who had an open surgical biopsy
      had a greater than the median diagnostic wait time, irrespective of detection
      method.

PMID- 24741471
TI  - Cultural heritage training in the US military.
AB  - Cultural competence is a vital component of many missions in today's military.
      Cultural competence enables one to further a mission, save resources, and save
      lives. Conversely, a lack of cultural competence may bring about challenges to
      mission completion, requirement for more resources, waste of resources, and
      destruction of lives. Cultural competence involves many components. One
      particular component is cultural heritage awareness and protection of cultural
      property. This study sought to assess current understanding of cultural property
      protection and determine the effectiveness of a training aimed at increasing
      cultural property protection awareness, knowledge, and comfort within the
      military setting. It was hypothesized that participants would vary in their level
      of awareness, knowledge, and comfort of cultural property protection, and that
      all would show a significant improvement in knowledge scores post training.
      Factors such as deployment experience were examined for potential correlation
      with measures such as awareness. A 14 question pre-read survey was developed to
      assess participants' demographics, awareness, knowledge, and comfort with
      cultural property protection. Awareness included value, laws, and procedures
      while knowledge examined "know how" such as how to bed down in a protected
      structure or communicate information about the structure. Comfort assessed one's
      comfort with engaging in the knowledge based tasks. A 24 question post read
      survey was administered to assess awareness, knowledge, and comfort, and to
      solicit additional feedback on the manual itself. The survey utilized a 1-5
      rating scale with 1 representing no awareness, knowledge, or comfort and 5
      representing absolute awareness, knowledge, and comfort with different aspects of
      cultural property protection. Cultural property protection value was highest pre
      and post training while knowledge regarding recovery of property was rated lowest
      pre and post training. Results are encouraging for the pursuit of cultural
      property education. Further studies should include knowledge assessment versus
      self rating as well as tracking of incidents and outcomes in the field.
      Implications for mission readiness and success are discussed. 

PMID- 24741472
TI  - Modelling temperature effects on milk production: a study on Holstein cows at a
      Japanese farm.
AB  - Milk yield and its composition vary according to individual cows as well as to a
      variety of different environment conditions, such as temperature. Previous
      studies suggest that heat exerts considerable negative effects on milk production
      and its composition, especially during summer months. We investigate the
      production and fat composition of milk from individual dairy cows and develop a
      modelling framework that investigates the effect of temperature by extending a
      traditional lactation curve model onto a more flexible statistical modelling
      framework, a generalised additive model (GAM). The GAM simultaneously copes with
      multiple different conditions (temperature, parity, days of lactation, etc.),
      and, importantly, their non-linear relationships. Our analysis of retrospective
      data suggests that individual cows respond differently to heat; cows producing
      relatively high quantities of milk tend to be particularly sensitive to heat. Our
      model also suggests that most dairy cows studied fall into three distinct cases
      that underpin the variation of the milk fat ratio by different mechanisms. 

PMID- 24741473
TI  - Analytical solutions for systems of partial differential-algebraic equations.
AB  - This work presents the application of the power series method (PSM) to find
      solutions of partial differential-algebraic equations (PDAEs). Two systems of
      index-one and index-three are solved to show that PSM can provide analytical
      solutions of PDAEs in convergent series form. What is more, we present the post
      treatment of the power series solutions with the Laplace-Pade (LP) resummation
      method as a useful strategy to find exact solutions. The main advantage of the
      proposed methodology is that the procedure is based on a few straightforward
      steps and it does not generate secular terms or depends of a perturbation
      parameter. 

PMID- 24741474
TI  - Host-specific assemblages typify gut microbial communities of related insect
      species.
AB  - Mutualisms between microbes and insects are ubiquitous and facilitate
      exploitation of various trophic niches by host insects. Dictyopterans (mantids,
      cockroaches and termites) exhibit trophisms that range from omnivory to strict
      wood-feeding and maintain beneficial symbioses with the obligate endosymbiont,
      Blattabacterium, and/or diverse gut microbiomes that include cellulolytic and
      diazotrophic microbes. While Blattabacterium in omnivorous Periplaneta is fully
      capable of provisioning essential amino acids, in wood-feeding dictyopterans it
      has lost many genes for their biosynthesis (Mastotermes and Cryptocercus) or is
      completely absent (Heterotermes). The conspicuous functional degradation and
      absence of Blattabacterium in most strict wood-feeding dictyopteran insects
      suggest that alternative means of acquiring nutrients limited in their diet are
      being employed. A 16S rRNA gene amplicon resequencing approach was used to deeply
      sample the composition and diversity of gut communities in related dictyopteran
      insects to explore the possibility of shifts in symbiont allegiances during
      termite and cockroach evolution. The gut microbiome of Periplaneta, which has a
      fully functional Blattabacterium, exhibited the greatest within-sample
      operational taxonomic unit (OTU) diversity and abundance variability than those
      of Mastotermes and Cryptocercus, whose Blattabacterium have shrunken genomes and
      reduced nutrient provisioning capabilities. Heterotermes lacks Blattabacterium
      and a single OTU that was 95% identical to a Bacteroidia-assigned diazotrophic
      endosymbiont of an anaerobic cellulolytic protist termite gut inhabitant samples
      consistently dominates its gut microbiome. Many host-specific OTUs were
      identified in all host genera, some of which had not been previously detected,
      indicating that deep sampling by pyrotag sequencing has revealed new taxa that
      remain to be functionally characterized. Further analysis is required to uncover
      how consistently detected taxa in the cockroach and termite gut microbiomes, as
      well as the total community, contribute to host diet choice and impact the fate
      of Blattabacterium in dictyopterans. 

PMID- 24741475
TI  - Lithopedion diagnosed during infertility workup: a case report.

PMID- 24741476
TI  - Positive effects of a novel non-peptidyl low molecular weight radical scavenger
      in renal ischemia/reperfusion: a preliminary report.
AB  - Ischemia/reperfusion (I/R) is one of the most common causes of acute kidney
      injury. Reactive oxygen species have been recognized to be an important
      contributor to the pathogenesis of I/R injury. We hypothesize that a non-peptidyl
      low molecular weight radical scavenger (IAC) therapy may counteract this factor,
      ultimately providing some protection after acute phase renal I/R injury. The aim
      of this preliminary study was to assess the ability of IAC to reduce acute kidney
      injury in C57BL/6 mice after 30-minute of bilateral ischemia followed by
      reperfusion. The rise in serum creatinine level was higher in C57BL/6 control
      mice after I/R when compared to IAC (1 mg)-treated mice. Control mice showed
      greater body weight loss compared to IAC-treated mice, and at pathology, reduced
      signs of tubular necrosis were also evident in IAC-treated mice. These
      preliminary evidences lay the basis for more comprehensive studies on the
      positive effects of IAC as a complementary therapeutic approach for acute phase
      renal I/R injury. 

PMID- 24741477
TI  - A handy approximation for a mediated bioelectrocatalysis process, related to
      Michaelis-Menten equation.
AB  - In this article, Perturbation Method (PM) is employed to obtain a handy
      approximate solution to the steady state nonlinear reaction diffusion equation
      containing a nonlinear term related to Michaelis-Menten of the enzymatic
      reaction. Comparing graphics between the approximate and exact solutions, it will
      be shown that the PM method is quite efficient. 

PMID- 24741478
TI  - Successful surgical in situ treatment of prosthetic graft infection by staged
      procedure after Bentall operation and total aortic arch replacement.
AB  - We report a case of a 29-year-old Marfan patient who developed prosthetic graft
      infection 10 months after Bentall operation and successive replacement of the
      remaining ascending aorta and the entire aortic arch for acute aortic dissection.
      Instead of an aggressive high-risk aortic redo procedure with removal and
      replacement of the infected prosthetic graft we elected a staged graft-sparing
      surgical approach. After 18 months of close follow-up the patient is in good
      condition and free from infectious sequela. This case and our review of the
      literature suggest that open extensive disinfection followed by tissue flap
      coverage is highly effective in controlling thoracic aortic prosthetic graft
      infection and may be considered as first-line treatment in such high-risk aortic
      arch redo patients. 

PMID- 24741479
TI  - Clinical trials in India: Way forward.

PMID- 24741480
TI  - Why are clinical trials necessary in India?
AB  - Clinical trials are emerging as an important activity in India as it is an
      essential component of the drug discovery and development program to which India
      is committed. The only robust way to evaluate a new medicine is by doing properly
      designed clinical trials. In addition to advancing science, clinical trials offer
      myriad benefits to the participants. The recent hue that created in India about
      clinical trials is probably an exaggeration of facts. However, these points to
      the need for ensuring proper compliance with the regulatory norms and proper
      training of concerned personnel in good clinical practice (GCP). This will ensure
      that India continues to reap the benefits of clinical trials and also become a
      world leader in this field. 

PMID- 24741481
TI  - Institutional review boards: Challenges and opportunities.
AB  - Institutional Review Boards (IRBs) are an important link in subject protection
      program, and their function defines ethical credentials of research. Of late
      there has been a furore in the country over the number of deaths in clinical
      research, and allegations of unethical research. Clinical trials have been
      discussed in medical and lay press and even in the parliament, these discussions
      called for strengthening the subject protection program. The Central Drug
      Standards and Control Organization (CDSCO), amended the Schedule Y, by issuing
      three amendments to introduce new compensation rules and registration of IRBs
      functioning in the country. IRBs in India face a variety of challenges, and need
      support from the regulators or independent experts. This is also an opportunity
      to revamp the subject protection program and strengthen the IRB functioning. An
      independent advisory body comprising of experts who have hands on experience in
      administering IRBs, is essential to provide support to IRBs in the country. This
      body should be independent of regulatory influence and work with IRBs to
      strengthen them. 

PMID- 24741482
TI  - Research ethics committees: Need for harmonization at the national level, the
      global and Indian perspective.
AB  - Ethics committee (EC) organization and standardization is an important aspect of
      clinical research. There is a healthy trend worldwide to register and/or accredit
      research ECs reviewing clinical research. This article tries to focus on the
      existing model of ECs worldwide, as against the Indian backdrop. The article
      reviews literature, journals, websites, and studies conducted in 10 different
      countries and outlines the working model of ECs in these countries. The
      challenges faced during the ethical review, especially in case of multicenter
      trials, have been identified. A solution has been suggested to overcome these
      challenges, and to ensure the overall smooth functioning of clinical trials. The
      article proposes the development of national and regional central ECs to counter
      the current drawbacks in the ethical review mechanisms in India. 

PMID- 24741483
TI  - Effects of botropase on clotting factors in healthy human volunteers.
AB  - OBJECTIVE: To evaluate the effects of botropase on various clotting factors in
      human volunteers. MATERIALS AND METHODS: It was a prospective open label study
      conducted on human healthy volunteers. After the baseline screening, subjects
      fulfilling inclusion criteria were enrolled. On the study day, 1 ml of botropase
      was administered intravenously and after an hour same dose of botropase (1 ml)
      was given by intramuscular (IM) route. The efficacy and safety parameters were
      monitored up to 72 h from the time of intravenous (IV) administration. RESULTS: A
      total of 15 volunteers, belonging to 24-35 years of age were included in the
      study. Botropase significantly reduced the plasma level of fibrinogen and fibrin
      degradation products after 5 min of IV administration (P < 0.05). In addition,
      factor X was observed to reduce constantly by botropase administration suggesting
      enhanced turnover between 5 and 20 min of IV administration. Although botropase
      reduced clotting and bleeding time in all the volunteers, the data remains to be
      statistically insignificant. CONCLUSION: Present study demonstrated the safety
      and efficacy of botropase in human healthy volunteers. The study has shown that
      it is a factor X activator and reduces effectively clotting and bleeding time.

PMID- 24741484
TI  - Effect of inhaled corticosteroids on systemic inflammation in asthma.
AB  - BACKGROUND: Recent research using serum high sensitivity C-reactive protein (hs
      CRP) has evidenced existence of low grade systemic inflammation in asthmatics
      whose correlation with various clinical indices is not fully studied. OBJECTIVE:
      To investigate the relationship between systemic inflammation and various
      clinical and treatment characteristics of asthma. MATERIALS AND METHODS: Forty
      asthmatics (22 steroid inhaling and 18 steroid naive) and 40 healthy subjects
      matched for age and sex were examined cross-sectionally. Along with clinical
      assessment, serum hs-CRP levels were measured for all subjects using latex
      enhanced immunoturbidometry method. RESULTS: Serum hs CRP levels were
      significantly higher in steroid naive asthmatics when compared to normal subjects
      (0.93 +/- 1.18 vs 0.24 +/- 0.31 mg/dL, respectively; Mann-Whitney U test, P <
      0.001). This association persisted after adjusting for age, gender, body mass
      index (BMI), and socioeconomic status (adjusted odds ratio 10.47; 95% CI 1.88
      58.3; P < 0.01). Steroid inhaling asthmatics had serum hs-CRP levels comparable
      with control group (0.17 +/- 0.18 vs 0.24 +/- 0.31 mg/dL respectively, P > 0.05).
      Among the clinical and treatment related variables, duration of inhaled steroids
      usage alone correlated significantly with serum hs-CRP levels (Pearson
      correlation coefficient r = 0.449, P < 0.05), which was independent of age, BMI,
      duration of illness, and frequency of emergency visits. CONCLUSION: This study
      confirms the existence of low grade systemic inflammation in asthma which is
      effectively controlled by inhaled steroids. Such an effect of inhaled steroids
      appears to be more pronounced in recent users than that of long-term users,
      possibly due to lower adherence rate among the latter.

PMID- 24741485
TI  - Effect of Carum carvi, a herbal bioenhancer on pharmacokinetics of antitubercular
      drugs: A study in healthy human volunteers.
AB  - AIM AND OBJECTIVES: The present study was undertaken in 20 healthy human
      volunteers to evaluate the effect of a herbal bioenhancer, Carum carvi on
      pharmacokinetics of rifampicin, isoniazid, and pyrazinamide in fixed dose
      combination (FDC). MATERIALS AND METHODS: It was a prospective, two-period, open
      label, cross-over experiment on 20 healthy human male volunteers. The volunteers
      were administered a single dose of FDC containing rifampicin (450 mg), isoniazid
      (300 mg), and pyrazinamide (1000 mg) and after 10 days washout period the same
      FDC along with C. carvi extract (100 mg) was administered. Blood samples were
      collected at different time-points and analyzed by high-performance liquid
      chromatography (HPLC). Detailed pharmacokinetic parameters were calculated, which
      included C max, area under curve (AUC), time to reach maximum plasma
      concentration (T max), clearance (Cl), volume of distribution (V d), and half
      life (t 1/2). RESULTS: Additions of C. carvi extract lead to increase in plasma
      levels of rifampicin, isoniazid, and pyrazinamide. The bioavailability indices C
      max of rifampicin increased from 4.57 +/- 0.19 to 5.95 +/- 0.19 (P = 0.000) and
      AUC increased from 40.11 +/- 1.69 to 53.01 +/- 1.88 (P = 0.000). Similarly, C max
      of isoniazid increased from 2.66 +/- 0.16 to 3.62 +/- 0.16 (P = 0.000) and AUC
      from 17.72 +/- 0.78 to 22.87 +/- 0.94 (P = 0.000). The bioavailability indices of
      pyrazinamide also revealed an increase in C max from 18.81 +/- 0.79 to 25.06 +/-
      1.14 (P = 0.000) and AUC from 107.65 +/- 4.42 to 137.71 +/- 5.92 (P = 0.000),
      respectively. CONCLUSION: C. carvi acts as a bioenhancer and modifies the
      kinetics of antitubercular treatment (ATT) favorably.

PMID- 24741486
TI  - Evaluation the effects of adding ketamine to morphine in intravenous patient
      controlled analgesia after orthopedic surgery.
AB  - BACKGROUND: Intravenous patient-controlled analgesia (PCA) with morphine is
      commonly used for post-operative pain after major surgery. Ketamine has analgesic
      property at lower doses, and in combination with opioids it could have
      synergistic effect. The aim of this study is to determine effects of the addition
      of ketamine to morphine for PCA after orthopedic surgery. MATERIALS AND METHODS:
      In this double-blind randomized clinical trial, 60 patients were randomly
      allocated to receive PCA consisting: Group 1 (morphine 0.2 mg/ml), Group 2
      (morphine 0.2 mg/ml + ketamine 1 mg/ml), and Group 3 (morphine 0.1 mg/ml +
      ketamine 2 mg/ml). In this, anesthesiologists managed study, patients had
      orthopedic surgery. Assessments were made at 24 h and 48 h post-operatively.
      Visual analog scale (VAS) was used for recording pain score. PCA morphine use was
      recorded at 24 h and 48 h. VAS scores over 48 h were analyzed with analysis of
      variance for repeated measures. Significance level was taken as 0.05. RESULTS:
      There is no significant difference between demographic information of the three
      groups (P > 0.05). Control of pain in Group 2 and Group 3 was better than in
      Group 1 (only morphine) (P = 0.001) but there was no significant difference
      between Group 2 and Group 3 (P > 0.05). Rate of narcotic consumption in groups 2
      and 3 was significantly lower than Group 1 (P < 0.05). CONCLUSION: After
      orthopedic surgery, the addition of ketamine to morphine for intravenous PCA was
      superior to Intravenous PCA opioid alone. The combination induces a significant
      reduction in pain score and cumulative morphine consumption.

PMID- 24741487
TI  - Up-dosing of non-sedating antihistamines in chronic urticaria: Need for well
      designed clinical trials in India.
AB  - Urticaria is a heterogeneous group of diseases. Chronic urticaria significantly
      impacts quality-of-life of patients. Second generation, non-sedating
      antihistamines are recommended as first line treatment for chronic spontaneous
      urticaria. In patients with inadequate control of symptoms, increase in dosage of
      non-sedating antihistamines up to four fold has been recommended. This
      recommendation is based on low cost, good safety and good evidence of efficacy of
      non-sedating, second generation antihistamines. This article reviewed Indian data
      on up-dosing of antihistamines in chronic urticaria. There is a need for well
      designed clinical trials with -up-dosing of individual antihistamines in Indian
      patients. 

PMID- 24741488
TI  - Development of pharmacoeconomics guidelines for India.

PMID- 24741489
TI  - Whats New in Critical Illness and Injury Science? Airway management: Is this as
      good as it gets?

PMID- 24741490
TI  - Evaluation of rapid response team implementation in medical emergencies: A
      gallant evidence based medicine initiative in developing countries for serious
      adverse events.
AB  - BACKGROUND: Rapid response team (RRT) has been implemented in developed countries
      with the aim of early recognition and response to critical care triggers for the
      better patient outcome. However, the data concerning their efficacy is hardly
      available until date from Indian subcontinent. AIMS: To evaluate the impact of
      RRT implementation on patient outcome during medical emergencies. SETTINGS AND
      DESIGN: Retrospective observational study of RRT records of in-bed patients of
      super specialty academic teaching hospital. MATERIALS AND METHODS: RRT record
      forms during the first half of the year from January 2012 to June 2012 were
      included for all inpatients and out-patients irrespective of their age, gender
      and diseases profile after their inclusion in the system. Outcomes such as
      patient stayed in the room, patient transfer to intensive care unit (ICU),
      patient discharge and generation of code blue event, mortality and length of stay
      in hospital/ICU were measured. STATISTICAL ANALYSIS: Descriptive analysis was
      performed with the help of statistical software STATA 9.0 and R 2.13.2 (StataCorp
      LP, Lakeway Drive College Station, Texas, USA). RESULTS: Analysis of 41 RRT calls
      showed decreased code blue calls by 2.44% and decrease in mortality by 4.88%.
      Average length of stay in ICU and hospital post RRT assistance for patients was
      2.55 and 6.95 days respectively. Conversely percentage of patients requiring a
      higher level of care was more (75.61%) than those who stayed in their rooms/wards
      (24.39%). CONCLUSION: Implementation of RRT in this hospital was associated with
      reduced code blue events and its attendant mortality outside the ICU settings.
      However, more number of patient requiring higher levels of care delineates the
      need for a larger evidence based medicine study.

PMID- 24741491
TI  - Evaluation of critical care outreach services in a tertiary care Hospital in
      India: A retrospective analysis.
AB  - BACKGROUND: Critical care outreach services (CCOS) is a relatively a new concept
      in India and is not as developed as in Western countries. Efficient utilization
      of limited intensive care service requires comprehensive CCOS. Appropriate
      activation of such services will limit excess burden on already scarce human
      resources. AIM: To evaluate the functioning of CCOS in a tertiary care hospital
      and also to identify factors leading to its overactivation. MATERIALS AND
      METHODS: Data of 400 calls received in resuscitation room (RR) of the Trauma
      Center during January 2011-June 2011 was analyzed. Categorical variables were
      summarized by calculating the frequency and percentage. Records of the department
      sending the call, purpose of the calls, and designation of the person sending the
      calls were noted. Calls were grouped into appropriate or inappropriate. RESULTS:
      Maximum calls were received from medicine wards (65.8%) followed by neurosurgery
      ward (12.5%). Of all, 26% of the calls were sent by senior doctors (senior
      resident), whereas 69.4% of the calls were sent by junior doctors. 66.2% of the
      calls were indicated for assessment and intensive care unit (ICU) transfer,
      whereas central venous/intravenous access constituted 14.8% of the calls.
      Intubation and ventilator settings constituted 7.3 and 7.8% calls, respectively.
      About one-third (36.2%) of all calls were inappropriate. CONCLUSION: There is
      inefficient use of human resources in CCOS in our hospital. Lack of objective
      activation criteria and inefficient training in basic lifesaving skills and
      ventilator know-how were identified as primary factors for the same.

PMID- 24741492
TI  - Clinico-epidemiological profile of poisoned patients in emergency department: A
      two and half year's single hospital experience.
AB  - CONTEXT: Poisoning is a common cause for attending emergency department of
      hospitals. AIMS: To explore the epidemiological characteristics and clinical
      profile of patients presenting with poisoning in emergency department. SETTINGS
      AND DESIGN: Prospective, cross-sectional, hospital-based study. MATERIALS AND
      METHODS: Relevant epidemiological and clinical data from patients, presenting
      with history/clinical features of poisoning in emergency department of a tertiary
      care district hospital in India, were collected and analyzed. STATISTICAL
      ANALYSIS: DATA ANALYSIS WAS DONE BY USING DESCRIPTIVE AND INFERENTIAL STATISTICAL
      METHODS: Frequency, percentage, mean, and standard deviation (SD). A two-tailed P
      < 0.05 was considered to be statistically significant. RESULTS: A total of 4,432
      patients with history and/clinical features of poisoning were included in the
      study. The females clearly outnumbered male patients. Poisoning with suicidal
      intent was more frequent (81.08%) than accidental (18.92%) (P < 0.0001). Majority
      of the patients were housewives followed by farmers, businessmen, laborers, and
      students. The mean time interval between poison consumption and admission to
      hospital was 6.4 hours (Mean +/- SD: 6.4 +/- 2.29). Snakebite (31.90%) was the
      most common cause of poisoning followed by organophosphorus compounds (21.84%),
      rodenticide (16.49%), alcohol (13.80%), chemicals (9.04%), and drugs (2.3%). The
      mean GCS (Glasgow Coma Scale) score of the poisoned patients at presentation was
      6.85 +/- 1.62. Of all the patients included in the study, 3,712 patients (83.76%)
      survived and 720 patients (16.24%) expired. CONCLUSIONS: The current piece of
      work suggests that most of the poisoning cases involved young age group
      particularly females. Snakebite and organophosphorus compounds contributed most
      of the poisoning cases which calls for urgent government initiatives for
      improvement in proper lighting of the district to prevent snakebite and
      controlled use of pesticides.

PMID- 24741493
TI  - Esophageal assessments of left ventricular filling pressures: A proof-of-concept
      study.
AB  - OBJECTIVE: We sought to evaluate if left ventricular filling pressures can be
      assessed from the esophagus. BACKGROUND: The invasive assessment of left
      ventricular filling pressures is of importance in the evaluation and monitoring
      of critically ill patients. The left atrium is in very close proximity to the
      esophagus. We hypothesized that the temporal pressure decay characteristics of an
      esophageal fluid volume positioned at the level ofthe left atrium should depend
      on the atrial and left ventricular filling pressure. MATERIALS AND METHODS: In
      five pigs an esophageal balloon was placed at the level ofthe left atrium. The
      balloon was then pressurized to 50 mmHg followed by an automated release that
      allowed us to directly record the pressure decay, while simultaneously recording
      left atrial pressures. An algorithm was developed to estimate atrial pressures.
      We also tested if invasive transesophageal atrial pressures can be recorded via
      an ultrasound guided left atrial puncture. RESULTS: Noninvasive transesophageal
      assessments of left atrial pressures are feasible. The left atrial pressure
      directly affects the esophageal pressure decay and correlates with the transition
      point from an exponential pressure decay to a more linear decay (r = 0.949). This
      approach also allows for the assessment of atrial waveforms. We could also
      demonstrate that invasive transesophageal pressure measurements are feasible and
      safe. CONCLUSIONS: The esophagus allows for reproducible less invasive
      assessments of left ventricular filling pressures and atrial pressure waveforms.
      This close spatial relationship provides an alternative access site for
      diagnostic and therapeutic cardiac procedures.

PMID- 24741494
TI  - Making endotracheal intubation easy and successful, particularly in unexpected
      difficult airway.
AB  - BACKGROUND: Difficult intubation, most often due to poor view of the vocal cords
      on laryngoscopy is an intermittent and often challenging problem for clinically
      practicing anesthesiologists, maxillofacial surgeons, ear nose, and throat (ENT),
      emergency, and critical care physicians. PURPOSE: We present a new approach for
      facilitating difficult intubation and evaluate its efficacy in a retrospective
      observational study. SETTINGS AND DESIGN: Operating room, emergency department,
      intensive care unit (ICU), retrospective observational study. MATERIALS AND
      METHODS: A semirigid 5.6 Rusch tracheal tube introducer (bougie) with its soft
      tip protruding at least 6 cm (=4 digits) beyond the distal end of the tube was
      used. After its insertion through the larynx under laryngoscopy, the tube was
      gently advanced upon rotation at 360 degrees  clockwise. STATISTICAL ANALYSIS:
      Descriptive. RESULTS: Anesthesia services were analyzed on 10,363 patients over
      12 months. In 2453 patients (23.7%) (Group A) intubated in the usual way,
      difficulties were encountered in 63 patients (2.6%). They were managed either
      with tube rotation technique (n = 60) or Bonfils endoscope (n = 3). In contrast,
      2807 patients (27.1%) (Group B) were intubated using tube rotation technique with
      introducer. Difficult intubations occurred only in three patients (0.11%) who
      could be managed with tube rotation by experienced consultant anesthesiologists.
      CONCLUSIONS: The tube rotation technique for intubation was introduced during the
      Gulf War and has been practiced for the past 19 years without any obvious damage
      to the trachea in Germany. However, it should be used only by physicians being
      well familiar with this technique. In addition, well designed controlled studies
      are needed.

PMID- 24741495
TI  - Assessment of performance and utility of mortality prediction models in a single
      Indian mixed tertiary intensive care unit.
AB  - OBJECTIVES: To assess the performance and utility of two mortality prediction
      models viz. Acute Physiology and Chronic Health Evaluation II (APACHE II) and
      Simplified Acute Physiology Score II (SAPS II) in a single Indian mixed tertiary
      intensive care unit (ICU). Secondary objectives were bench-marking and setting a
      base line for research. MATERIALS AND METHODS: In this observational cohort, data
      needed for calculation of both scores were prospectively collected for all
      consecutive admissions to 28-bedded ICU in the year 2011. After excluding
      readmissions, discharges within 24 h and age <18 years, the records of 1543
      patients were analyzed using appropriate statistical methods. RESULTS: Both
      models overpredicted mortality in this cohort [standardized mortality ratio (SMR)
      0.88 +/- 0.05 and 0.95 +/- 0.06 using APACHE II and SAPS II respectively].
      Patterns of predicted mortality had strong association with true mortality (R (2)
      = 0.98 for APACHE II and R (2) = 0.99 for SAPS II). Both models performed poorly
      in formal Hosmer-Lemeshow goodness-of-fit testing (Chi-square = 12.8 (P = 0.03)
      for APACHE II, Chi-square = 26.6 (P = 0.001) for SAPS II) but showed good
      discrimination (area under receiver operating characteristic curve 0.86 +/- 0.013
      SE (P < 0.001) and 0.83 +/- 0.013 SE (P < 0.001) for APACHE II and SAPS II,
      respectively). There were wide variations in SMRs calculated for subgroups based
      on International Classification of Disease, 10(th) edition (standard deviation +/
      0.27 for APACHE II and 0.30 for SAPS II). INTERPRETATION AND CONCLUSION: Lack of
      fit of data to the models and wide variation in SMRs in subgroups put a
      limitation on utility of these models as tools for assessing quality of care and
      comparing performances of different units without customization. Considering
      comparable performance and simplicity of use, efforts should be made to adapt
      SAPS II.

PMID- 24741496
TI  - Videolaryngoscopy.
AB  - The approach to airway management has undergone a dramatic transformation since
      the advent of videolaryngoscopy (VL). Videolaryngoscopes have quickly gained
      popularity as an intubation device in a variety of clinical scenarios and
      settings, as well as in the hands of airway experts and non-experts. Their
      indirect view of upper airway improves glottic visualization, including in
      suspected or encountered difficult intubation. Yet, more studies are needed to
      determine whether VL actually improves endotracheal intubation (ETI) success
      rates, intubation times, and first attempt success rates; and thereby a potential
      replacement to traditional direct laryngoscopy. Furthermore, advances in
      technology have heralded a wide array of models each with their own strengths,
      weaknesses, and optimal applications. Such limitations need to be better
      understood and alternative strategies should be available. Thus, the role of VL
      continues to evolve. Though it is clear VL expands the armamentarium not only for
      anesthesiologists, but all healthcare providers potentially involved in airway
      management. 

PMID- 24741497
TI  - Rapid-sequence intubation and cricoid pressure.
AB  - Airway management is the most important clinical skill for anesthesiologist,
      emergency physician, and other providers who are involved in oxygenation and
      ventilation of the lungs. Rapid-sequence intubation is the preferred method to
      secure airway in patients who are at risk for aspiration because it results in
      rapid unconsciousness (induction) and neuromuscular blockade (paralysis).
      Application of cricoid pressure (CP) for patients undergoing rapid-sequence
      intubation is controversial. Multiple specialty societies have recommended that
      CP is not effective in preventing aspiration; rather it may worsen laryngoscopic
      view and impair bag-valve mask ventilation. Some experts think that CP should be
      applied in trauma and patients at risk for aspiration; however CP, if necessary,
      should be altered or removed to facilitate intubation. 

PMID- 24741498
TI  - Airway management in cervical spine injury.
AB  - To minimize risk of spinal cord injury, airway management providers must
      understand the anatomic and functional relationship between the airway, cervical
      column, and spinal cord. Patients with known or suspected cervical spine injury
      may require emergent intubation for airway protection and ventilatory support or
      elective intubation for surgery with or without rigid neck stabilization (i.e.,
      halo). To provide safe and efficient care in these patients, practitioners must
      identify high-risk patients, be comfortable with available methods of airway
      adjuncts, and know how airway maneuvers, neck stabilization, and positioning
      affect the cervical spine. This review discusses the risks and benefits of
      various airway management strategies as well as specific concerns that affect
      patients with known or suspected cervical spine injury. 

PMID- 24741499
TI  - Advances in prehospital airway management.
AB  - Prehospital airway management is a key component of emergency responders and
      remains an important task of Emergency Medical Service (EMS) systems worldwide.
      The most advanced airway management techniques involving placement of
      oropharyngeal airways such as the Laryngeal Mask Airway or endotracheal tube.
      Endotracheal tube placement success is a common measure of out-of-hospital airway
      management quality. Regional variation in regard to training, education, and
      procedural exposure may be the major contributor to the findings in success and
      patient outcome. In studies demonstrating poor outcomes related to prehospital
      attempted endotracheal intubation (ETI), both training and skill level of the
      provider are usually often low. Research supports a relationship between the
      number of intubation experiences and ETI success. National standards for
      certification of emergency medicine provider are in general too low to guarantee
      good success rate in emergency airway management by paramedics and physicians.
      Some paramedic training programs require more intense airway training above the
      national standard and some EMS systems in Europe staff their system with
      anesthesia providers instead. ETI remains the cornerstone of definitive
      prehospital airway management, However, ETI is not without risk and outcomes data
      remains controversial. Many systems may benefit from more input and guidance by
      the anesthesia department, which have higher volumes of airway management
      procedures and extensive training and experience not just with training of airway
      management but also with different airway management techniques and adjuncts. 

PMID- 24741500
TI  - Pediatric airway management.
AB  - Securing an airway is a vital task for the anesthesiologist. The pediatric
      patients have significant anatomical and physiological differences compared with
      adults, which impact on the techniques and tools that the anesthesiologist might
      choose to provide safe and effective control of the airway. Furthermore, there
      are a number of pathological processes, typically seen in the pediatric
      population, which present unique anatomical or functional difficulties in airway
      management. The presence of one of these syndromes or conditions can predict a
      "difficult airway." Many instruments and devices are currently available which
      have been designed to aid in airway management. Some of these have been adapted
      from adult designs, but in many cases require alterations in technique to account
      for the anatomical and physiological differences of the pediatric patient. This
      review focuses on assessment and management of pediatric airway and highlights
      the unique challenges encountered in children. 

PMID- 24741501
TI  - Surgical airway.
AB  - Close to 3% of all intubation attempts are considered difficult airways, for
      which a plan for a surgical airway should be considered. Our article provides an
      overview of the different types of surgical airways. This article provides a
      comprehensive review of the main types of surgical airways, relevant anatomy,
      necessary equipment, indications and contraindications, preparation and
      positioning, technique, complications, and tips for management. It is important
      to remember that the placement of a surgical airway is a lifesaving procedure and
      should be considered in any setting when one "cannot intubate, cannot ventilate".

PMID- 24741503
TI  - Benefits of thrombolytics in prolonged cardiac arrest and hypothermia over its
      bleeding risk.
AB  - A 52-year-old non-smoking Caucasian male, who was admitted to our emergency room
      after he was found unconscious in the bathroom, went into cardiac arrest
      requiring prolonged cardiopulmonary resuscitation (CPR) and hypothermia therapy.
      Cardiac catheterization showed non-obstructive coronary arteries and further
      bedside echocardiogram suggested probable pulmonary embolism (PE) as an
      underlying cause of cardiac arrest. Although thrombolytic therapy is an effective
      therapy for PE, it is not routinely given during prolonged CPR for its life-
      threatening bleeding complications. Many reported cases have suggested a
      beneficial effect of empiric thrombolytic in cardiac arrest, but unrelated to
      duration of resuscitation and adjuvant treatments that imposes bleeding risk. We
      suspect that tissue plasminogen activator (tPA) should be promptly given to
      prolonged cardiac arrest patients, even when bleeding risk is high with the
      concurrent hypothermia treatment, keeping the benefits over risk strategy. Our
      patient received thrombolytic, tPA and showed remarkable clinical, physiological
      and radiographical improvement. 

PMID- 24741502
TI  - Extraglottic airway devices: A review.
AB  - Extraglottic airway devices (EAD) have become an integral part of anesthetic care
      since their introduction into clinical practice 25 years ago and have been used
      safely hundreds of millions of times, worldwide. They are an important first
      option for difficult ventilation during both in-hospital and out-of-hospital
      difficult airway management and can be utilized as a conduit for tracheal
      intubation either blindly or assisted by another technology (fiberoptic
      endoscopy, lightwand). Thus, the EAD may be the most versatile single airway
      technique in the airway management toolbox. However, despite their utility,
      knowledge regarding specific devices and the supporting data for their use is of
      paramount importance to patient's safety. In this review, number of commercially
      available EADs are discussed and the reported benefits and potential pitfalls are
      highlighted. 

PMID- 24741504
TI  - Panic attack: An unusual cause of spontaneous pneumomediastinum.

PMID- 24741505
TI  - Accidental penetrating chest injury with concealed retained wooden stick: A
      diagnostic dilemma and management.

PMID- 24741506
TI  - Health economics in India: The case of diabetes mellitus.

PMID- 24741507
TI  - Untapped diamonds for untamed diabetes: The alpha-glucosidase inhibitors.

PMID- 24741508
TI  - Diabetes and related remedies in medieval Persian medicine.
AB  - Diabetes Mellitus is a common metabolic disorder presenting increased amounts of
      serum glucose and will cover 5.4% of population by year 2025. Accordingly, this
      review was performed to gather and discuss the stand points on diagnosis,
      pathophysiology, non-pharmacological therapy and drug management of diabetes this
      disorder as described in medieval Persian medicine. To this, reports on diabetes
      were collected and analyzed from selected medical and pharmaceutical textbooks of
      Traditional Persian Medicine. A search on databases as Pubmed, Sciencedirect,
      Scopus and Google scholar was also performed to reconfirm the Anti diabetic
      activities of reported herbs. The term, Ziabites, was used to describe what is
      now spoken as diabetes. It was reported that Ziabites, is highly associated with
      kidney function. Etiologically, Ziabites was characterized as kidney hot or cold
      dystemperament as well as diffusion of fluid from other organs such as liver and
      intestines into the kidneys. This disorder was categorized into main types as hot
      (Ziabites-e-har) and cold (Ziabites-e-barid) as well as sweet urine (Bole-e
      shirin). Most medieval cite signs of Ziabites were remarked as unusual and
      excessive thirst, frequent urination and polydipsia. On the management, life
      style modification and observing the essential rules of prevention in Persian
      medicine as well as herbal therapy and special simple manipulations were
      recommended. Current investigation was done to clarify the knowledge of medieval
      scientists on diabetes and related interventions. Reported remedies which are
      based on centuries of experience might be of beneficial for- further studies to
      the management of diabetes. 

PMID- 24741509
TI  - Gynecomastia: Clinical evaluation and management.
AB  - Gynecomastia is the benign enlargement of male breast glandular tissue and is the
      most common breast condition in males. At least 30% of males will be affected
      during their life. Since it causes anxiety, psychosocial discomfort and fear of
      breast cancer, early diagnostic evaluation is important and patients usually seek
      medical attention. Gynecomastia was reported to cause an imbalance between
      estrogen and androgen action or an increased estrogen to androgen ratio, due to
      increased estrogen production, decreased androgen production or both. Evaluation
      of gynecomastia must include a detailed medical history, clinical examination,
      specific blood tests, imaging and tissue sampling. Individual treatment
      requirements can range from simple reassurance to medical treatment or even
      surgery. The main aim of any intervention is to relieve the symptoms and exclude
      other etiological factors. 

PMID- 24741510
TI  - Type 1 diabetes and osteoporosis: A review of literature.
AB  - With better care and intensive insulin therapy, microvascular complications have
      reduced and longevity has increased in patients with type 1 diabetes (T1DM).
      Therefore, there is a need to change the focus from microvascular complications
      to cardiovascular disease and osteoporosis. Though number of studies from other
      parts of the world show that patients with T1DM are at increased risk of
      osteoporosis and fractures, there is a paucity of data from India. A number of
      factors and mechanisms affecting bone health in patients with T1DM have been
      proposed. The main defect in genesis of osteoporosis is osteoblastic function,
      rather than osteoclastic overfunction. Assessment of bone mineral density by dual
      X-ray absorptiometry and other risk factors for osteoporosis, as a part of
      diagnostic procedure can help to design tailored treatment plans. A physically
      active healthy lifestyle, prevention of diabetic complications and adequate
      calcium and vitamin D supplementation are the mainstay for prevention of
      osteoporosis. Treatment of osteoporosis is not evidence based but it is proposed
      to be similar to osteoporosis associated with other conditions. Bisphosphonates
      are the mainstay for treatment of osteoporosis in patients with T1DM. However,
      more studies are needed to make definitive guidelines on prevention and treatment
      of osteoporosis in patients with T1DM. 

PMID- 24741511
TI  - Treat-to-target trials in diabetes.
AB  - Treat-to-target is a therapeutic concept that considers well defined and specific
      physiologic targets as aims in controlling the pathophysiology of the disease. It
      has been widely used in diseases that pathophysiology includes, chronic metabolic
      and physiological disturbances, namely rheumatic conditions, vascular medicine
      and diabetes. In diabetes, the availability of "gold-standard" quantitative
      measures like fasting plasma glucose and glycated hemoglobin make the application
      of treat-to-target trials especially pertinent. Treatment modalities which have
      used single therapeutic agents or combinations or in combination with a variety
      of titration algorithms and implementation protocols have broadened our
      understanding of diabetes management with specific reference to insulin
      initiation and maintenance. Treat-to-target trials have been used to investigate
      a wide variety of questions including efficacy, safety, effect of treatment on
      comorbidities and patient satisfaction, ideal mechanisms to implement insulin
      initiation etc. A more generalized acceptance and implementation of treat-to
      target trials may finally revolutionize diabetes management by combining aspects
      of individual care with standard treatment protocols. 

PMID- 24741512
TI  - Evaluation of sexual dysfunction in women with type 2 diabetes.
AB  - BACKGROUND: Sexual dysfunction is a common complication of diabetes that
      adversely affects their quality of life. Its prevalence is known to be higher in
      diabetic men with and it is estimated to affect 20-85% of patients but the
      problem is probably less common in diabetic women. This study investigated the
      prevalence of sexual dysfunction and its risk factors among women with diabetes.
      MATERIALS AND METHODS: This descriptive-analytic study was performed during May
      2012 to Feb 2013 at Diabetes clinic of Shahid Beheshti Hospital of Qom and The
      Female Sexual Function Index (FSFI) was used for evaluation of sexual
      dysfunction. CONCLUSION: In this study, 59 (53.6%) women had sexual dysfunction.
      The mean age of patients with sexual dysfunction and healthy people was 48.22 +/-
      6.61 and 48.14 +/- 5.37 years respectively and it was not statistically different
      in both groups (P = 0.94). Also, there was no significant difference between two
      groups in average duration of diabetes, fasting blood sugar (FBS), glycosylated
      hemoglobin (HbA1c) level, insulin resistance, abdominal circumference and body
      mass index BMI. Although the history of hypertension, coronary artery disease and
      exercise levels were not significantly associated with sexual dysfunction, but
      there was a significant association between albuminuria and sexual dysfunction (P
      = 0.001). Retinopathy and sexual dysfunction had statistically significant
      relationship (P = 0.007) while no association was found between diabetic
      neuropathy and sexual dysfunction (P = 0.79). RESULTS: Sexual dysfunction is a
      common complication in diabetic patients which accompanies with some
      complications of diabetes and should be considered especially in patients with
      nephropathy or retinopathy.

PMID- 24741513
TI  - Comparative evaluation of sonographic ovarian morphology of Indian women with
      polycystic ovary syndrome versus those of normal women.
AB  - OBJECTIVES: To study ovarian morphology by ultrasound in women with or without
      polycystic ovary syndrome (PCOS) and to establish cut-off values of these
      parameters in Indian women with PCOS. MATERIALS AND METHODS: A total of 119
      consecutive women diagnosed PCOS and 77 apparently healthy women were enrolled.
      Transabdominal ultrasound examination was carried out to assess ovarian volume,
      stromal echogenecity, follicle number and size. Cut-off values of the above
      ovarian parameters with sensitivity, specificity, positive predictive value (PPV)
      and negative predictive values (NPV) were calculated. RESULTS: Sensitivity of
      79.49% and specificity of 90.67% was achieved with a cut-off of 8 mL as ovarian
      volume. A cut-off value of 9 follicles to distinguish between PCOS and control
      women yielded a sensitivity of 82.35% and specificity of 92.0% while as a
      follicular size of 5 mm yielded sensitivity and specificity of 74.67% and 78.15%
      respectively. With all the three parameters sensitivity was 87.39% and
      specificity 87.84% with 92.04% PPV and 81.25% NPV. CONCLUSION: Using two or three
      sonographic criteria in combination improves sensitivity and helps diagnose
      additional patients with PCOS. Our results are at variance with the established
      cut-off values highlighting the fact that American Society for Reproductive
      Medicine consensus cut-off values are not reproducible in Indian context.

PMID- 24741514
TI  - Clinical features of bone metastasis for differentiated thyroid carcinoma: A
      study of 21 patients from a Tunisian center.
AB  - INTRODUCTION: The differentiated thyroid cancers have a good prognosis unless the
      presence of metastasis. These distant metastases, especially in bone, are a major
      cause of impaired quality of life and death requiring intensive management. The
      aim of our work was to study the patients' data, the disease characteristics and
      to analyze the therapeutic management of these patients. RESULTS: This study
      concerned a cohort of 21 patients treated for differentiated thyroid cancer
      during the period from 1995 to 2011. Eighteen of our patients were aged over 45
      years. A majority of them had follicular carcinoma. Bone metastases were often
      multiple and located at the axial skeleton. They were associated with other types
      of metastases, especially lung metastasis. A majority of patients received 131I
      treatment, following surgery or external beam radiotherapy for a palliative
      purpose. Overall survival was 65% at 5 years and 49% at 10 years. A long-term
      survival was achieved in 10% of the patients benefiting from a multidisciplinary
      care adapted to each case. CONCLUSION: Bone metastases often have a pejorative
      turning in the natural history of differentiated thyroid cancers. The right
      selection of individuals with better prognosis, for whom more aggressive curative
      treatment was indicated, requires a better understanding of the features of bone
      involvement.

PMID- 24741515
TI  - Circulating adiponectin levels in Indian patients with psoriasis and its relation
      to metabolic syndrome.
AB  - BACKGROUND: Adiponectin is a cytokine mainly secreted from the adipose tissue,
      which has insulin-sensitizing effects, antiatherosclerotic actions, and
      antiinflammatory properties. There are a few studies that have demonstrated that
      adiponectin is reduced in patients with psoriasis suggesting that this
      adipocytokine may have a role in the pathogenesis of psoriasis. There have been
      no studies so far on adiponectin in relation to psoriasis and metabolic syndrome
      (MetS). OBJECTIVES: This study was performed to analyze serum adiponectin and
      insulin levels in psoriasis patients with and without MetS and in controls with
      and without MetS. MATERIALS AND METHODS: We performed a case control study on 60
      psoriasis patients, 29 with MetS and 31 without MetS and 40 controls, 20 with and
      20 without MetS, matched for age, sex, and body mass index (BMI). Fasting serum
      insulin and adiponectin levels were measured in all groups. RESULTS: The overall
      serum adiponectin levels were significantly reduced in psoriasis patients when
      compared with controls (P = 0.000). A significant reduction was also observed in
      psoriasis patients with MetS than those without MetS in the same group (P =
      0.000). Similar decrease was observed between those with MetS in the psoriasis
      and control groups (P = 0.001). The lowest mean value of serum adiponectin
      (6387.9 ng/ml) was observed in psoriasis with MetS group and highest value
      (12146.3 ng/ml) in controls without MetS. CONCLUSION: Adiponectin levels are
      decreased in psoriasis patients irrespective of MetS thus indicating a role in
      its pathogenesis. This study prompts future trials on drugs increasing
      adiponectin levels in patients with psoriasis.

PMID- 24741516
TI  - Hepatitis C virus infection in Egyptian children with type 1 diabetes mellitus: A
      single center study.
AB  - BACKGROUND: Only few studies have evaluated the epidemiology and risk factors of
      hepatitis C virus (HCV) infection in Egyptian children with type 1 diabetes
      mellitus (T1DM). The present study aimed at measurement of the rates of anti-HCV
      positivity by Enzyme-Linked Immuno-Sorbent Assay (ELISA) test and of HCV
      Ribonucleic acid (RNA) positivity by polymerase chain reaction (PCR) among
      children with T1DM and to study the possible risk factors of infection. SETTINGS
      AND DESIGN: Cross-sectional controlled study. MATERIALS AND METHODS: The study
      included 150 children with T1DM (Group 1) (mean age 14. 76 +/- 6.4 years). Fifty
      children age and sex-matched were included as control group (Group 2) (mean age
      13.62 +/- 2.11 years). They were screened for HCV antibodies using third
      generation ELISA and HCV-RNA positivity by PCR. RESULTS: The frequency of anti
      HCV positivity by ELISA was significantly higher in children with T1DM (n = 150)
      in comparison wiith control group (n = 50) (12% vs 6%; P<0.001), while the
      frequency of HCV-RNA positivity by PCR among the cases testing positive by ELISA
      was 75% for both diabetic group and control group. There were no significant
      differences in serum levels of liver biochemical profile in diabetic children
      with anti-HCV positivity (n = 18) in comparison to those with anti-HCV negativity
      (n = 132). Residence in rural area, low socioeconomic class and prior
      hospitalization were significant risk factors for anti-HCV positivity by ELISA.
      CONCLUSIONS: The frequency of HCV infection in children with T1DM in Upper Egypt
      appears to be high and is mainly related to residence in rural area, low
      socioeconomic class and prior hospitalization. HCV infection in these children is
      not associated with significant changes in hepatic biochemical parameters.
      RECOMMENDATIONS: Implementation of strict infection control measures are highly
      recommended to reduce the frequency of HCV infection. Furthermore, the silent
      evolution of HCV infection in children makes periodic screening of HCV in
      diabetic children mandatory.

PMID- 24741517
TI  - The potential impact of family history of metabolic syndrome and risk of type 2
      diabetes mellitus: In a highly endogamous population.
AB  - AIM: This study aims to determine the potential impact of positive family history
      of Metabolic Syndrome (MetS) among two generations, on developing Type 2 Diabetes
      Mellitus (T2DM) and the potential relation of consanguineous marriage among
      patients with MetS to the risk of developing T2DM among a sample of Qataris.
      DESIGN: A cross-sectional study. SETTING: Primary healthcare (PHC) centers.
      MATERIALS AND METHODS: The survey and measurement were conducted from April 2011
      to December 2012 among Qatari nationals above 20 years of age. Of the 2,182
      subjects, who were approached to participate in the study, 1,552 (71%) gave their
      consent. Face-to-face interviews were conducted using a structured questionnaire
      followed by anthropometric measurements and laboratory tests. Metabolic syndrome
      was defined using the National Cholesterol Education Program-Third Adult
      Treatment Panel (ATP III) as well as International Diabetes Federation (IDF).
      RESULTS: Overall, the prevalence of MetS was 26.2% according to ATP III and 36.9%
      according to IDF (P < 0.0001). The mean age of MetS patients with T2DM was
      significantly higher than those without T2DM (Mean 48 +/- 9.9 vs. 42.5 +/- 9.2; P
      < 0.001). The proportion of females was higher among MetS patients with T2DM as
      compared to those without T2DM (61% vs. 51%; P = 0.053). In addition, there were
      significant differences between MetS patients with and without DM in terms of co
      morbidities of hypertension, coronary heart disease, and high cholesterol. The
      proportion of MetS patients with positive family history for MetS was
      significantly higher in MetS patients with T2DM as compared to those without T2DM
      (46.7% vs. 33.8%; P = 0.009). The proportion of positive family history of MetS
      among fathers (35% vs. 21.9%; P = 0.005), mothers (30.5% vs. 18.8%; P = 0.008),
      maternal aunt (18.3% vs. 11.2%; P = 0.055), and maternal grand father (19.5% vs.
      10%; P = 0.010) were significantly higher in MetS patients with T2DM as compared
      to the counterpart. The proportion of consanguineous marriages was almost two
      times higher among MetS patients with T2DM as compared to those without T2DM
      (80.9% vs. 41.9%; P < 0.001). The proportion of MetS patients with T2DM was lower
      than MetS patients without DM below 45 years, but after 45 years, the proportion
      of MetS patients with T2DM remained higher than their counterparts. CONCLUSION:
      Family history of MetS among parents, maternal aunt, maternal grandfather, and
      consanguineous marriages among patients of MetS are significantly associated with
      the development of T2DM in Qatar. These results support the necessity of earlier
      screening for T2DM among MetS patients with positive family history of MetS.

PMID- 24741518
TI  - Intraoperative parathyroid hormone assay-cutting the Gordian knot.
AB  - BACKGROUND: Hyperparathyroidism is treated by surgical excision of the
      hyperfunctioning parathyroid gland. In case of adenoma the single abnormal gland
      is removed, while in hyperplasias, a subtotal excision, that is, three-and-a-half
      of the four glands are removed. This therapeutic decision is made
      intraoperatively through frozen section evaluation and is sometimes problematic,
      due to a histological overlap between hyperplasia and the adenoma. The
      intraoperative parathyroid hormone (IOPTH) assay, propogated in recent years,
      offers an elegant solution, with a high success rate, due to its ability to
      identify the removal of all hyperfunctioning parathyroid tissue. AIM: To study
      the feasibility of using IOPTH in our setting. MATERIALS AND METHODS: Seven
      patients undergoing surgery for primary hyperparathyroidism had their IOPTH
      levels evaluated, along with the routine frozen and paraffin sections. RESULTS:
      All seven patients showed more than a 50% intraoperative fall in serum PTH after
      excision of the abnormal gland. This was indicative of an adenoma and was
      confirmed by histopathological examination and normalization of serum calcium
      postoperatively. CONCLUSION: The intraoperative parathyroid hormone is a
      sensitive and specific guide to a complete removal of the abnormal parathyroid
      tissue. It can be incorporated without difficulty as an intraoperative guide and
      is superior to frozen section diagnosis in parathyroid surgery.

PMID- 24741519
TI  - Congenital hypothyroidism in neonates.
AB  - CONTEXT: Congenital hypothyroidism (CH) is one of the most common preventable
      causes of mental retardation in children and it occurs in approximately 1:2,000
      1:4,000 newborns. AIMS AND OBJECTIVES: The aim of this study is to determine the
      frequency of CH in neonates. SETTINGS AND DESIGN: This cross-sectional study was
      conducted in neonatal units of the Department of Pediatrics Unit-I, King Edward
      Medical University/Mayo Hospital, Lahore and Lady Willington Hospital Lahore in 6
      months (January-June 2011). MATERIALS AND METHODS: Sample was collected by non
      probability purposive sampling. After consent, 550 newborn were registered for
      the study. Demographic data and relevant history was recorded. After aseptic
      measures, 2-3 ml venous blood analyzed for thyroid-stimulating hormone (TSH)
      level by immunoradiometric assay. Treatment was started according to the
      individual merit as per protocol. STATISTICAL ANALYSIS USED: Data was analyzed by
      SPSS 17 and Chi-square test was applied to find out the association of CH with
      different variables. RESULTS: The study population consisted of 550 newborns.
      Among 550 newborns, 4 (0.8%) newborns had elevated TSH level. CH had
      statistically significant association with mother's hypothyroidism (P value
      0.000) and mother's drug intake during the pregnancy period (P value 0.013).
      CONCLUSION: CH is 0.8% in neonates. It has statistically significant association
      with mother's hypothyroidism and mother's drug intake during pregnancy.

PMID- 24741520
TI  - An observational study of cutaneous manifestations in diabetes mellitus in a
      tertiary care Hospital of Eastern India.
AB  - BACKGROUND: Diabetes mellitus and its impact on the human body have been
      extensively dissected over the years. However, skin which is the largest organ in
      the body, has received minimum attention. Therefore, this study was designed to
      analyze the prevalence and pattern of skin disorders among diabetic patients from
      Eastern region of India. MATERIALS AND METHODS: This is an observational study,
      conducted in the General Medicine and Endocrinology departments of a Medical
      College and Hospital in Eastern India. The data were collected prospectively and
      systematically in a pre-established proforma designed by us, where clinical
      findings along with investigations were recorded. RESULTS: Six hundred and eighty
      (680) diabetic patients were examined, there were (64.8%) male and (35.1%) were
      female, of them 95.3% were Type 2 diabetics while 4.7% were Type 1. Five hundred
      and three patients (503) out of six hundred and eighty. i.e. 73.9% were found to
      have skin lesions. Thirteen (13) (41%) Type1 diabetics demonstrated skin lesions
      commonest being diabetic xerosis, infections and diabetic hand. Among Type2
      diabetics 490(75.61%) showed skin lesions. Here infections, xerosis, hair loss
      beneath the knees, diabetic dermopathy were the most frequent. Majority of
      patients (67%) had combination of more than one type of skin lesion. There was
      statistically significant correlation of skin lesions with duration of diabetes,
      however similar correlation could not be demonstrated regarding metabolic
      control. CONCLUSION: Involvement of skin is inevitable and multifarious in
      diabetes mellitus. Higher prevalence is seen in Type 2 diabetic population. The
      duration of diabetes is positively correlated with lesions and infective
      dermatologic manifestations were associated with higher HbA1C values.

PMID- 24741521
TI  - Correlation between serum adiponectin and clinical characteristics, biochemical
      parameters in Indian women with polycystic ovary syndrome.
AB  - BACKGROUND: Polycystic ovary syndrome (PCOS) is a common disorder. PCOS women are
      at a high risk for insulin resistance and metabolic syndrome (MS). Adiponectin is
      positively related to insulin sensitivity. It has a preventive role in
      atherogenesis and MS. The present work was conducted to study the correlation
      between serum adiponectin levels and clinical characteristics and biochemical
      parameters in PCOS patients. MATERIALS AND METHODS: A prospective study in 49
      newly diagnosed (as per Rotterdam criteria) Indian PCOS women was conducted. PCOS
      women were clinically examined and investigated for biochemical parameters.
      RESULTS: The mean serum adiponectin was 12 +/- 9.4 MUg/mL (range 0.47-45).
      Hypoadiponectinemia (serum adiponectin <4 MUg/mL) was present in 22% patients.
      Age and adiponectin correlated significantly and inversely (r = -0.42, P =
      0.027). Overweight/obese patients had lower mean adiponectin levels than normal
      weight (11.62 +/- 9.5 vs 13.58 +/- 9.5, P = 0.56). It was significantly lower in
      patients with acanthosis nigricans (AN) as compared with those without AN (8.4 +/
      5.9 vs 15 +/- 11, P = 0.038). Hirsute patients showed lower mean adiponectin
      levels than nonhirsute (10 +/- 7.3 vs 13 +/- 10, P = 0.57). A positive,
      insignificant correlation was observed between serum adiponectin and cholesterol,
      low-density lipoprotein, follicle stimulating hormone (FSH), thyroid stimulating
      hormone, levels. A negative insignificant correlation existed between serum
      adiponectin and luteinizing hormone (LH), LH: FSH ratio, prolactin,
      dehydroepiandrosterone, testosterone, triglyceride, high-density lipoprotein,
      fasting blood glucose, fasting insulin, and Homeostasis Model Assessment.
      CONCLUSION: Hypoadiponectinemia is present in one-fifth of women with PCOS.
      Adiponectin levels decrease as age advances. Low levels of adiponectin possibly
      contributes to the development of dermal manifestation (AN) of insulin
      resistance.

PMID- 24741522
TI  - Endocrinology and the arts at the feet of the dancing Lord: Parathyroid hormone
      resistance in an Indian icon.
AB  - The dance of Siva has a cosmic appeal. Nowhere has this dance been crystallised
      in its pristine form as in the Nataraja Bronzes from the Chola period. Mysticism
      surrounds the dancing form of the Nataraja. But does Nataraja dance upon an
      endocrine mystery. Does the demon under his feet Apasmara literally forgetfulness
      or epilepsy have an endocrine disorder. The short limbed stocky eye popping dwarf
      with possible mental retardation with a name that suggests epilepsy throws open a
      host of endocrine diagnoses. From cretinisim to the original descriptions of
      pseudohypoparathyroidism here is one view of the medical mystery under Shiva's
      dancing feet. 

PMID- 24741523
TI  - Brain death in ICU patients: Clinical significance of endocrine changes.
AB  - Numerous studies have been carried out among patients admitted in intensive care
      unit (ICU) having primary endocrine pathology, endocrine manifestations of
      systemic diseases or post-endocrine tissue surgery. However, minimal literary
      evidence is available highlighting the endocrine changes occurring during brain
      death in critically ill patients. A precise and timely diagnosis of brain death
      is required to convey the relatives about the prognosis and also to possibly plan
      for organ retrieval for transplantation purposes. The diagnosis of this condition
      as of today remains largely a clinical one. Brain death is associated with a
      multitude of endocrinological alterations which are yet to be completely
      unraveled and understood. Evaluating these endocrinological modifications lends
      us an added vista to add to the existing clinical parameters which might help us
      to confirm the diagnosis of brain death with a higher degree of precision.
      Moreover, since the efficacy of hormone replacement therapy to benefit in organ
      retrieval remains yet unproven, newer diagnostic modalities and research studies
      are definitely called for to strategize the optimal dosage and duration of such
      therapies. 

PMID- 24741524
TI  - Pituitary apoplexy presenting as myocardial infarction.
AB  - We describe a male patient who presented with sudden onset severe headache and
      right sided ptosis that was diagnosed to be secondary to pituitary apoplexy on
      the background of diabetes mellitus. This was complicated by left ventricular
      failure and acute coronary syndrome. The case highlights the importance of
      considering hypocortisolism/hypopituitarism as an important and rare precipitant
      of an acute coronary event as occurred in the case. 

PMID- 24741525
TI  - A case report of reactive hypoglycemia in a patient with pheochromocytoma and
      it's review of literature.
AB  - Pheochromocytoma, a tumor characterized by catecholamine excess, is usually
      associated with impaired glucose tolerance. Hypoglycemia may occur after the
      abrupt withdrawal of catecholamines in the postoperative period. Rarely, insulin
      secretion by stimulation of beta-2 adrenoreceptors may overwhelm the glucagon
      production, thereby causing hypoglycemia. Here, we describe a female with
      pheochromocytoma, who presented with postprandial hypoglycemia. 

PMID- 24741526
TI  - A rare case of triple thyroid ectopia.
AB  - Various anomalies of thyro-glossal duct have been described, in which the duct
      may form a cyst or may present as a solid nodule to form an ectopic gland. The
      ectopic gland can develop along the tract of the duct to give rise to ectopic
      lingual, sublingual (pre-hyoid) or sub-hyoid (pyramidal) gland, with or without
      normal pre-tracheal thyroid gland.There are a few reports of double ectopia of
      thyroid but triple ectopia of thyroid is extremely rare. We have come across a
      case of triple thyroid ectopia, i.e., thyroid tissue at three locations along the
      tract of descent of thyro-glossal duct on CT, which hast been rarely reported in
      the world literature, and hence this report. 

PMID- 24741527
TI  - Effect of octreotide on endometriosis in acromegaly: Case report with review of
      literature.
AB  - OBJECTIVE: To study the effect of octreotide therapy on endometriotic lesions in
      a patient with coexisting endometriosis and acromegaly. INTERVENTION PATIENT: A
      34-year-old female was diagnosed with acromegaly and coexisting endometriosis.
      Post-surgical resection of the tumor, patient was initiated on octreotide
      therapy. RESULTS: There was improvement in menstrual bleeding as IGF1 levels
      decreased with Octreotide therapy. Resolution of the endometriotic lesions was
      observed during follow up. CONCLUSION: In this unusual case, the treatment of
      acromegaly concurred with regression in the endometriotic lesions. Causal or
      incidental association cannot be inferred from the present case.

PMID- 24741528
TI  - Comment on trends in onomastics-the case of PCOS by Kalra et al.

PMID- 24741529
TI  - Response to the editorial on "Defining vitamin D deficiency, using surrogate
      markers".

PMID- 24741530
TI  - Redefining vitamin D deficiency: Reply to comments.

PMID- 24741532
TI  - Dextrose Gel is Superior to Feeding Alone in Neonatal Hypoglycemia.

PMID- 24741533
TI  - High-flow Nasal Cannulae in Very Preterm Infants after Extubation.

PMID- 24741531
TI  - Predicting disease severity of necrotizing enterocolitis: how to identify infants
      for future novel therapies.
AB  - Necrotizing enterocolitis (NEC) remains a very devastating problem within the
      very low birth weight neonatal population. Several experimental therapies are
      being tested in animal models and soon may be ready for human trials. Despite
      this progress, we currently have no way to identify infants who would be optimal
      targets for therapy. Specifically, we are unable to predict which infants will
      progress to the more severe Bell's stage of disease that may necessitate surgery.
      Ideally, an algorithm could be constructed that would encompass multiple neonatal
      and maternal risk factors as well as potential biologic markers of disease so
      that these infants could be identified in a more timely fashion. This review
      summarizes the known risk factors and biomarkers of disease in hopes of
      stimulating clinical research to identify such an "early warning" NEC algorithm. 

PMID- 24741534
TI  - Early Enteral Prophylactic iron Supplementation May be Preferred in Preterm Very
      Low Birth Weight Infants.

PMID- 24741535
TI  - Stool calprotectin in necrotizing enterocolitis.
AB  - BACKGROUND: Calprotectin is a 36 kDa protein present in the cytoplasm of the
      neutrophil has antimicrobial and apoptosis inducing activities. In vitro studies
      have shown that calprotectin inhibits the growth of various microorganisms.
      Necrotizing enterocolitis (NEC) remains one of the leading causes of morbidity
      and mortality in neonatal intensive care units (NICU), affecting up to 5% of
      premature infants. Fecal calprotectin is resistant to degradation and has been
      proposed as a useful marker of gastrointestinal inflammation. OBJECTIVE: The
      objective of the present study is to evaluate fecal calprotectin concentrations
      in NEC. STUDY DESIGN: Fifteen neonates with a clinical diagnosis of NEC were
      studied; they admitted at NICU of Zagazig University Hospital. In addition, 20
      age sex matched neonates fed all caloric requirement served as the control group.
      All neonates were subjected to history taking, clinical examination, laboratory
      investigations (complete blood count, C-reactive protein) and determination of
      stool calprotectin. RESULTS: There was a highly significant increase in fecal
      calprotectin in patients than control and there was a highly significant increase
      in its fecal level in died patients than living one. Also significant increase in
      fecal calprotectin level with increasing severity of NEC. CONCLUSION: Fecal
      calprotectin measurements could be a valuable tool for the investigation of
      preterm and full term infants suspected of having NEC.

PMID- 24741536
TI  - Retinopathy of prematurity: risk factors and role of antenatal betamethasone in
      Indian preterm newborn babies.
AB  - BACKGROUND: Increase in the survival of preterm neonates has led to increased
      incidence of retinopathy of prematurity (ROP). Among various risk factors, only
      prematurity is well-established and role of others is still not clear. Effect of
      antenatal betamethasone on ROP severity is also controversial. Available
      literature from India has a paucity of information. OBJECTIVES: (a) The primary
      aim of the following study is to find the incidence and risk factors of ROP and
      (b) secondary aim is to assess the effect of antenatal betamethasone on ROP.
      DESIGN: prospective, observational cohort study. SETTING: Tertiary level neonatal
      care unit. MATERIALS AND METHODS: A total of 148 infants <= 34 weeks gestation at
      birth, completed the study protocol. Severe ROP was defined as stage II and
      higher (including plus disease) of ROP. Various perinatal factors including
      antenatal betamethasone were analyzed by univariate followed by multivariate
      analysis. RESULTS: overall incidence of ROP (any stage) was 44.6%. Severe ROP was
      mainly detected in <1200 g birth weight and/or <30 weeks gestational age.
      Antenatal betamethasone was associated with non-severe form of ROP (P < 0.05) on
      univariate analysis, but could not pass multivariate logistic regression
      analysis. Among other perinatal factors studied, low birth weight (<1200 g) (odds
      ratio [OR]: 19.699, 95% confidence interval [CI]: 2.42-160.17, P = 0.005), low
      gestational age (<30 weeks) (OR: 36.52, 95% CI: 3.76-354.3, P = 0.002), acidosis
      (OR: 6.932, 95% CI: 1.16-41.33, P = 0.034) and blood transfusion (OR: 14.11, 95%
      CI: 1.494-133.5, P = 0.021) were associated with babies in severe ROP in an
      independent manner. CONCLUSIONS: Low birth weight and low gestational age emerged
      as independent significant risk factors along with blood transfusion and
      acidosis. Antenatal betamethasone may be preventive for severe ROP. More studies
      are however recommended.

PMID- 24741537
TI  - Perception and expectation of iran neonatal transport expert regard to developing
      neonatal transport system in iran: a qualitative research.
AB  - INTRODUCTION: This study was aimed to reach expert's expectations of neonatal
      transport system for developing neonatal transport system in Iran. MATERIALS AND
      METHODS: This is a qualitative study conducted by using focus group discussion
      (FGD) to present expert's perspectives and expectancy about neonatal transport
      system. Participants was selected from all experts and specialist about neonatal
      transport in Iran countryside. Finally 48 experts, participate in this study. To
      data collection 4 FGD were conducted, data were analyzed by content analyses. All
      subthemes were categorized in main themes according to conceptual relationship as
      an expert panels opinions. In order to comply with the ethical issues involved in
      the study was voluntary, also permission for the recording session were taken and
      confidentiality was also ensured. RESULT: According to FGD results, 11 themes and
      90 subthemes were founded related to neonatal transport system, the main
      identified themes included: Aims, necessity and models of neonatal transport
      system, organizing the transport system, management and quality of instruments in
      the transport system, Neonatal transport system staff, Human resource management
      and issue related to human resources, conditions and requirements of neonatal
      transport system, facilitating factors in neonatal transport system, information
      management and communication system and weakness of neonatal transport system.
      CONCLUSION: Neonatal transport systems in different countries must adapted
      according to situation and component of each country have different strength and
      weakness and in implementing a system must attend to geographical conditions,
      financial ability and access to professionals, health system structure,
      facilities related to neonatal health care, antenatal services in regain, health
      care related, health care program about neonates and pregnant women and
      epidemiological status and mortality and morbidity in deferent locals and regains
      in countryside.

PMID- 24741538
TI  - Glucose levels in newborns with special reference to hypoglycemia: a study from
      rural India.
AB  - Hypoglycemia is one of the common metabolic problems in neonatal medicine. There
      is association between blood glucose levels and neurological development. The
      study involved 100 mothers and neonates blood glucose levels were measured using
      a standard glucometer in mother delivering babies within half an hour of delivery
      and in newborns at 0, 3, 6, 12, 24 h of life. Blood glucose levels were low at
      0(th) and 6(th) h and maximum at 24(th) h. Neonates born to mothers with high
      maternal blood glucose levels were hypoglycemic showing a negative correlation.
      The mean blood glucose levels were low in pre-term and post-term compared with
      term babies and range of blood glucose levels were wide in preterm and post term
      babies. 

PMID- 24741539
TI  - Suppurative parotitis and submandibular sialadenitis.
AB  - Suppurative involvement of salivary gland in neonates is a rare disorder. Parotid
      gland being the most commonly involved. We described a case of suppurative
      parotitis leading to abscess formation and subsequent involvement of the
      submandibular gland. Incision and drainage of the abscess was performed, most of
      the purulent material was drained. Symptoms and signs resolved within 2 days. Pus
      culture grew Staphylococcus aureus. 

PMID- 24741540
TI  - Congenital tuberculosis complicated by interstitial pulmonary emphysema.
AB  - We report a case of congenital tuberculosis, a rare entity itself; complicated by
      pulmonary interstitial emphysema, thus leading to air entrapment in lungs and
      prolonged oxygen dependence. The diagnosis of congenital tuberculosis is often
      missed and under-reported due to low index of suspicion and less sensitivity of
      diagnostic tools. 

PMID- 24741541
TI  - Poland's Syndrome with Absent Limb Anomalies.
AB  - Poland's syndrome comprises a spectrum of chest-wall deformities affecting, to
      various degrees, the rib cage, the chest-wall muscles, neurovascular structures
      of the ipsilateral arm and the overlying breast. We present a neonate with
      features of depressed right chest-wall with no respiratory distress. Computed
      tomography showed hypolasia of the right pectoralis major muscle, with reduced
      subcutaneous fat on the ipsilateral side of the chest, with abnormalities of the
      ribs on the same side but absent upper limb deformities. There is negative
      history of other family members of being affected. 

PMID- 24741542
TI  - Cephalothoracoomphalopagus: a rare type of conjoined twin.
AB  - We present a case of female cephalothoracoomphalopagus conjoind twin, which is
      extremely rare type of conjoined twins. We also review the contemprory knowledge
      regarding incidence, etiopathogenesis, antenatal diagnosis and outcone or the
      prognosis of conjoint twins. The case belong to hindu female, no history of
      consanguineous marriage, ingestion of drugs or exposure to any radiation. History
      of one abortion and one twin delivery present. Conjoind twin was
      cephalothoracoomphalopagus type, delivered vaginaly at 30 wks of gestion to a 25
      yrs old multigravida. Management of conjoind twin still remain challenges because
      of multiple congenital anomalies and poor outcome is seen. 

PMID- 24741543
TI  - Lethal progressive thoracic insufficiency in a neonate due to jarcho levin
      syndrome.
AB  - A rare case of Jarcho Levin syndrome (JLS) presenting as a lethal progressive
      respiratory insufficiency in early neonatal period is reported. The neonate had
      classical features of this syndrome including vertebral segmentation defects,
      typical costo-vertebral fusion defects and scoliosis resulting in small thoracic
      volume and limited chest expansion; all consistent with a clinical diagnosis of
      JLS with thoracic insufficiency. In addition, our case had a rare association of
      dextrocardia and acyanotic congenital heart disease. 

PMID- 24741544
TI  - A rare association of pyloric stenosis and situs inversus: impact on diagnosis
      and treatment.
AB  - A rare case of 23 days old boy is reported having congenital hypertrophic pyloric
      stenosis with situs inversus. Incidentally detected secondary diagnosis obscured
      the primary diagnosis by altering the physical examination findings. Diagnosis
      was made by ultrasonography (USG) which revealed congenital hypertrophic pyloric
      stenosis with situs inversus. Clinical details, diagnosis and management are
      discussed. 

PMID- 24741545
TI  - An unusual association of microcephalic osteodysplastic primordial dwarfism type
      I with cardiac and brain anomalies.
AB  - Less than 100 cases of primordial dwarfism have been reported worldwide out of
      which Microcephalic osteodysplastic primordial dwarfism type I comprise about <30
      cases. We report a rare case of extreme growth failure in a neonate with
      primordial dwarfism of antenatal onset due to Microcephalic osteodysplastic
      primordial dwarfism type I. Our case is also unique in being associated with
      hitertho unreported association of subpulmonic ventricular septal defect and a
      dorsal interhemispheric cyst in the brain. 

PMID- 24741546
TI  - Maple syrup urine disease and oculocutaneous albinism in twins.

PMID- 24741547
TI  - A sporadic case of klippel-feil syndrome type 2.

PMID- 24741548
TI  - Canagliflozin: A Novel SGLT2 Inhibitor for Type 2 Diabetes Mellitus.
AB  - Diabetes Mellitus continues to be a major non- communicable disease with global
      burden of 366 million at present and projected to increase to 439 to 552 million
      by 2030, India being the hub of diabetes. Sodium glucose transporter 2 (SGLT2)
      inhibitors presents a new class of anti-diabetic drugs having an insulin
      independent mechanism that offers a considerable advantage of increasing urinary
      glucose excretion without inducing hypoglycemia and promoting weight loss due to
      loss of 300 to 400kcal/day, Canagliflozin being the 1(st) successful candidate of
      this group and became the first SGLT2 inhibitor to be FDA approved on March 29,
      2013. In various clinical trials, it has shown promising results in controlling
      glycemia, causing weight loss, reducing systolic and diastolic BP and
      cardiovascular risk. There are some safety concerns associated with its use e.g.
      genital mycotic infections, increased urination, urinary tract infection and
      hyperkalemia, which need to be carefully addressed while using this drug. 

PMID- 24741549
TI  - The two sides of opioids in cyclical vomiting syndrome.
AB  - BACKGROUND: Cyclical vomiting syndrome is increasingly recognized in adults, with
      recent reports suggesting 'coalescing attacks' in one third of the patients. We
      hypothesized that the common need for opioid treatment may contribute to
      coalescing attacks through development of opioid dependence and withdrawal,
      triggering cyclical vomiting syndrome. AIM: This study was to review iatrogenic
      opioid dependence as the potential cause for triggering cyclical vomiting
      syndrome. MATERIALS AND METHODS: A retrospective review was performed to identify
      patients treated for cyclical vomiting syndrome by a single physician between Jan
      and December of 2010. Demographic data, clinical presentation, treatment,
      cumulative opioid prescription during hospitalizations and emergency room visits
      and days of inpatient stay were abstracted from the chart. RESULTS: Forty-one
      patients (mean age 37.5.6 +/- 2.6 years; 66% female) were seen within this
      timeframe. In eleven patients (27%) with ongoing opioid use, the initial cyclical
      illness had progressed and eventually coalesced. A cohort of 23 patients was
      followed for at least 6 months (12.3 +/- 1.7 months). The best single predictor
      of repeat hospitalizations was the cumulative opioid dosage. CONCLUSION:
      Continued use of opioid therapy is a poor prognostic marker of cyclical vomiting
      syndrome and may contribute to disease coalescence, with dependence and
      withdrawal triggering recurrent episodes.

PMID- 24741550
TI  - Factors influencing medical students' choice of future specialization in medical
      sciences: a cross-sectional questionnaire survey from medical schools in china,
      malaysia and regions of South asian association for regional cooperation.
AB  - BACKGROUND: In future, increase in the number of healthcare professionals is
      dependent on the career interest among present undergraduate medical students.
      Based on their interest to pursue their specialty, the availability of medical
      doctors in each specialty could be done. AIMS: This study was to find out future
      career interest and factors that influence undergraduate medical students to
      choose their future specialization. MATERIALS AND METHODS: The study was carried
      out among first-year medical students from five countries. The students were
      asked to complete an 8-item questionnaire. Two thousand one hundred fifty three
      participants were enrolled in the study. Data were analyzed in Microsoft-Excel
      and Statistical Package for the Social Sciences. RESULTS: Of the 2153
      participants, only 1470 responded. Among the 1470 participants, 169 participants
      were excluded due to the ambiguity in responses, finally making it to
      1301participants. Among them, Anatomy (49.3%) followed by Biochemistry (26.7%)
      and Physiology (24%) were the most preferred subjects. CONCLUSIONS: Anatomy was
      the most preferred basic science subject among the other subjects and the
      students were interested to pursuing surgery in future. Furthermore, the most
      preferred future specialties were surgery, internal medicine and pediatrics with
      gender variations; males preferring surgery and females in obstetrics and
      gynecology.

PMID- 24741551
TI  - Prevalence of temporomandibular disorder in children and adolescents from public
      schools in southern portugal.
AB  - BACKGROUND: The prevalence of temporomandibular disorder (TMD) in children and
      adolescents is in the range of 6-68% and can be triggered or aggravated by
      emotional stress. AIM: The study was to investigate the prevalence of TMD in
      Portuguese children and adolescents and its association with emotional stress.
      MATERIALS AND METHODS: The sample comprised 3,260 students aged 5-19 years. The
      questionnaire was used to assess the presence of TMD, and was applied in a single
      moment. RESULTS: TMD was observed in 821 (25.2%) students. The most common
      symptoms of TMD were: if considered tense or nervous (52%), have headaches
      (36.8%), and habit of clenching or grinding teeth (27.3%). The girls had a 1.36
      higher probability of developing TMD than boys (95% CI: 1.14-1.63; p < 0.001);
      moreover, students from the older age group had a 2.31 higher probability of
      developing the disorder (95% CI: 1.85-2.89; p < 0.001). Students who considered
      themselves tense or nervous presented 8.74 higher probability (95% CI: 7.03
      10.86; p < 0.001) of developing TMD. CONCLUSION: This study showed a high
      prevalence of TMD in children and adolescents in southern Portugal, and revealed
      a significant association between this dysfunction and the levels of emotional
      stress. Female students, older students, and those considered tense or nervous
      have a higher probability of developing TMD.

PMID- 24741552
TI  - Ovarian granulosa cell tumor: clinical features, treatment, outcome, and
      prognostic factors.
AB  - BACKGROUND: Granulosa cell tumors are rare neoplasms characterized by long
      natural history and favorable prognosis. AIMS: The objective of this study was to
      determine the clinical presentation, treatment, outcome, and prognostic factors
      for patients of granulosa cell tumors. MATERIALS AND METHODS: A retrospective
      analysis of 26 patients of granulosa cell tumor of ovary from 2002 to 2011 was
      carried out. The records of all patients were analyzed to determine clinical
      presentation, treatment, survival, and prognostic factors. RESULTS: The median
      age of the patients was 50 years (range, 17-71 years). Abdominal pain was the
      most common presenting symptom. The median follow-up was 71.4 months (range, 21.6
      149.9 months). The estimated 5 and 10 year overall survival (OS) was 84.6 and
      72.5%, respectively. Event-free survival (EFS) was 76.5 and 52.9% at 5 and 10
      years, respectively. Advanced stage was significant independent poor prognostic
      indicator for both OS and EFS. CONCLUSION: Majority of the patients with
      granulosa cell tumors of the ovary present in early stage. Surgery is the primary
      treatment modality for granulosa cell tumors. Advanced stage and presence of
      residual disease were associated with inferior survival, but only prospective
      studies can ascertain their definite role.

PMID- 24741553
TI  - Relationship between Type 2 Diabetic Retinopathy and Periodontal Disease in
      Iranian Adults.
AB  - BACKGROUND: Periodontal disease in diabetic patients can compromise a patient's
      ability to maintain a proper metabolic control and may be associated with
      diabetic complication. AIMS: This study was designed to evaluate the frequency of
      periodontal disease in patients with type 2 diabetes mellitus (DM) and how this
      was related with the presence of diabetic retinopathy (DR). MATERIALS AND
      METHODS: A comparison was made of periodontal parameters (plaque index (PI),
      community periodontal index of treatment needs (CPITN), periodontal disease
      severity measured in quartiles of probing depth (PD), and clinical attachment
      loss (CAL)) in a group of diabetic patients with retinopathy (n = 84) versus a
      group of diabetic patients without retinopathy (n = 129). In addition, 73 age-
      and sex-matched individuals were selected to serve as the control group. Analysis
      was performed to evaluate the relationships between periodontal disease and DR.
      RESULTS: In terms of PI, no statistically significant differences were observed,
      so, oral hygiene was similar in both groups. Diabetic patients with retinopathy
      had greater CPITN (P < 0.001) and more severe periodontal disease (P < 0.001)
      than no retinopathy. Also, our results indicated a relationship between type 2 DM
      and periodontal disease. CONCLUSIONS: The patients with diabetes retinopathy
      appear to show increased periodontal disease susceptibility.

PMID- 24741554
TI  - Slow yogic breathing through right and left nostril influences sympathovagal
      balance, heart rate variability, and cardiovascular risks in young adults.
AB  - BACKGROUND: Specific nostril breathing is known to influence autonomic functions.
      AIM: The study was to assess the effects of right nostril breathing (RNB) and
      left nostril breathing (LNB) on heart rate variability (HRV) and cardiovascular
      functions. MATERIAL AND METHODS: Eighty-five student volunteers were divided into
      three groups: RNB group (n = 30), LNB group (n = 30), and control group (n = 25).
      RNB and LNB group subjects practiced right and left nostril breathing,
      respectively, every day 1 h for 6 weeks. The control group did not practice
      nostril breathing. Cardiovascular parameters and spectral indices of HRV were
      recorded before and after 6-week practice of nostril breathing. In RNB and LNB
      groups, prediction of rate-pressure product (RPP) by low-frequency to high
      frequency ratio (LF-HF) of HRV was assessed by bivariate logistic regression.
      RESULTS: HRV indices representing sympathetic activity were increased in the RNB
      group and indices representing parasympathetic activity were increased in LNB
      group following 6-week nostril breathing. Prediction of LF-HF to RPP, the marker
      of cardiovascular risks, was more significant (OR 2.65, P = 0.005) in the LNB
      group compared to the RNB group (OR 1.452, P = 0.016). CONCLUSIONS: Short-term
      practice of LNB improves vagal tone, increases HRV, and promotes cardiovascular
      health of medical students. Practice of RNB increases sympathetic tone and could
      jeopardize cardiovascular health.

PMID- 24741555
TI  - Synchronous metastasis of prostate adenocarcinoma to the stomach and colon: a
      case report.
AB  - CONTEXT: Prostate cancer is the leading cancer diagnosis in males. The most
      common metastatic site of metastases in patients with prostate cancer is the
      axial skeleton and local lymph nodes. Rarely has there been a description of
      metastatic prostate cancer to the stomach, esophagus, small bowel, and rectum.
      CASE REPORT: We report an unusual case of a patient who was diagnosed with
      prostate cancer with synchronous metastasis to both the stomach and sigmoid
      colon. A 71-year-old African American man with a history of prostate cancer was
      admitted with a hemoglobin level of 6.1 g/dl, which had decreased from the
      baseline value of 8 g/dl. He underwent an esophagogastroduodenoscopy, which
      revealed a nodule in the fundus of stomach; a biopsy of the nodule was done. The
      patient also underwent a sigmoid polypectomy. Both surgical specimens were
      histopathologically consistent with metastatic adenocarcinoma of prostatic
      origin. CONCLUSION: To the best of our knowledge, this is the first case report
      in literature of synchronous metastasis of prostate cancer to both the stomach
      and sigmoid colon.

PMID- 24741556
TI  - Quality Assurance for African Laboratories: How Soon can this be Accomplished?

PMID- 24741557
TI  - Western blot: protein transfer overview.

PMID- 24741558
TI  - Western blot: technique, theory and trouble shooting.

PMID- 24741559
TI  - Stroke epidemiology in Thailand.
AB  - Stroke is a major health burden in Thailand. It is the leading cause of death and
      long term disability in both men and women. Despite the improvement of healthcare
      system, the mortality rate of stroke is still increasing during the past 5 years.
      The incidence of stroke in Thailand is now being studied in a large population
      based cohort. The prevalence of stroke is estimated to be 1.88% among adults 45
      years and older. Stroke is more prevalent in men than in women and the mean age
      of stroke onset is 65 years. Hypertension, diabetes, dyslipidemia, metabolic
      syndrome, and atrial fibrillation are major risk factors of stroke in the Thai
      population. Evolution from predominantly rural to urbanized industrial
      communities result in the increasing prevalence of these risk factors. Similar to
      other parts of the world, ischemic stroke is the most common stroke type but the
      proportion of hemorrhagic stroke is higher when compared to Caucasian
      populations. Among patients with ischemic stroke, lacunar stroke is most common,
      accounting for almost half followed by atherosclerotic disease. Intracranial
      atherosclerosis is also prevalent in Thai population. For acute treatment,
      intravenous thrombolysis has been used in Thailand for over 20 years. Its cost is
      reimbursed by the national health care system but its use is still limited. With
      the introduction of the stroke fast track system, prompt stroke treatment across
      the country is warranted. Stroke unit is now the standard of care in large
      regional and provincial hospitals. 

PMID- 24741560
TI  - Ischemic stroke subtype classification: an asian viewpoint.
AB  - Proper classification of the causative mechanism of stroke is important for
      optimizing stroke treatment and assessing prognosis. The primary etiology of
      stroke differs according to race and ethnicity: emboli originating from the heart
      or extracranial large arteries are common in Western populations, whereas small
      vessel occlusion or intracranial atherosclerosis is more prevalent in Asians.
      Intracranial atherosclerosis frequently leads to stroke by branch-artery
      occlusion, and the degree of stenosis in these cases is often <50%. Mild
      intracranial atherosclerotic stenosis may cause distal embolization, if the
      atherosclerotic plaque is sufficiently vulnerable. Moreover, high-resolution
      magnetic resonance imaging studies have identified small plaques causing
      infarction, even in patients with normal-appearing vascular findings. Such cases,
      which are prevalent in Asia, could not be classified as large-artery
      atherosclerosis by previous classification systems. Additionally, single
      subcortical infarctions, which are usually attributed to lipohyalinotic small
      vessel disease, can have other causes, including microatheroma of perforators and
      atherothrombotic lesions at the parental artery. Single subcortical infarctions
      associated with parental artery disease or those bordering on the main vessel
      more often have atherosclerotic characteristics than do those associated with
      lipohyalinosis of the penetrating artery. In countries where intracranial
      atherosclerosis is common, such atherosclerotic single subcortical infarctions
      are predicted to be prevalent. These cases, however, could not be appropriately
      classified in previous systems. Further effort should be devoted to formulate
      ischemic stroke classification systems that adequately incorporate results of
      recent studies and reflect the underling pathologic mechanisms, especially in
      patients with single subcortical infarction and intracranial atherosclerosis. 

PMID- 24741561
TI  - Recent updates on subcortical ischemic vascular dementia.
AB  - Vascular dementia (VaD) is a history-laden disease entity that dates back to the
      19th century when arteriosclerotic brain atrophy due to hardening of the arteries
      was perceived as the major cause of senile dementia. Its existence had been
      overshadowed by the emergence of Alzheimer's disease (AD) in the past century and
      research on AD dominated the field of dementia. Interest in VaD has been revived
      in recent years as vascular lesions have been shown to make great contributions
      to the development of dementia, particularly in the elderly. VaD has now evolved
      into the concept of vascular cognitive impairment (VCI), which encompasses not
      only VaD but also AD with cerebrovascular disorder and VCI with no dementia. The
      concept of VCI is intended to maximize the therapeutic potential in dementia
      management because the vascular component may be amenable to therapeutic
      intervention particularly in the early stages of cognitive impairment.
      Subcortical ischemic vascular dementia (SIVD) is pathologically driven by severe
      stenosis and the occlusion of small vessels that culminate into white matter
      ischemia and multiple lacunar infarctions in the subcortical structures. The
      relatively slow progression of symptoms and clinical manifestations associated
      with cholinergic deficits often make the differentiation of SIVD from AD
      difficult. The recent development of in vivo amyloid imaging enabled further
      pathological breakdown of SIVD into pure SIVD and mixed dementia with subcortical
      ischemia based on the absence or existence of amyloid pathology in the brain. In
      this article, the authors reviewed the emerging concepts of VaD/VCI and the
      clinical manifestations, biomarkers, treatments, and preclinical models of SIVD
      based on the pathophysiologic mechanisms of the disease. 

PMID- 24741562
TI  - Intracranial atherosclerosis: current understanding and perspectives.
AB  - The importance of intracranial atherosclerotic disease (ICAD) as a cause of
      stroke is underscored as compared to that of extracranial carotid stenosis and
      nonvalvular atrial fibrillation. Recent large clinical trials of ICAD, which
      evaluated the effectiveness of anticoagulation and stenting to prevent
      thromboembolism and restore hemodynamic compromise, failed to reduce major
      vascular events in patients with ICAD. These trials showed the importance of
      optimal control of risk factors to reduce major vascular events in these
      patients. Recent advances in risk factors for ICAD are summarized, together with
      possible reasons for race-ethnic differences in the prevalence of ICAD. In
      addition, the failure of the major clinical trials of ICAD may be caused by
      limitations in the understanding of ICAD. Unlike in patients with extracranial
      carotid stenosis or atrial fibrillation, stroke associated with ICAD occurs in
      association with various stroke mechanisms such as in situ thrombotic occlusion,
      artery-to-artery embolism, hemodynamic insufficiency, and branch occlusion. In
      clinical trials of ICAD, patients with all these types of ICAD were included.
      However, treatment effects may differ among the different types of ICAD.
      Treatment strategies might be selected based on clinical features (including the
      time after onset) and serologic and neuroimaging biomarkers (including diffusion
      weighted image pattern and plaque images). Additional clinical trials considering
      these features are needed. 

PMID- 24741563
TI  - Symptomatic steno-occlusion in patients with acute cerebral infarction:
      prevalence, distribution, and functional outcome.
AB  - BACKGROUND AND PURPOSE: Symptomatic steno-occlusion (SYSO) in acute ischemic
      stroke has a significant impact on treatment options and prognosis. However, the
      prevalence, distribution, clinical characteristics, and outcome of SYSO are not
      well known. METHODS: We retrospectively identified 3,451 patients hospitalized
      because of ischemic stroke within 24 hours of symptom onset at 9 stroke centers
      in South Korea. Patients who did not undergo magnetic resonance imaging were
      excluded. SYSO was defined as stenosis or occlusion of cerebral arteries with
      relevant ischemic lesions in the corresponding arterial territory. The number,
      location, and severity of SYSOs and their effects on functional outcome were
      analyzed. RESULTS: In total, 1,929 of 3,057 subjects (63.1%) had SYSO. The most
      frequently affected vessels were the middle cerebral artery (34.6%), extracranial
      internal carotid artery (14%), vertebral artery (12.4%), and basilar artery
      (8.7%). SYSO predicted poor outcome on the modified Rankin Scale 3-6 (odds ratio,
      1.77; 95% confidence interval, 1.46-2.15) with adjustments. Involvement of 2 or
      more vessels was observed in 30.6% of patients with SYSO and independently
      increased the risk of poor outcome (odds ratio, 2.76; 95% confidence interval,
      2.12-3.59). The severity of SYSO was associated with outcome and showed a
      significant dose-response trend (P<0.001). The effect of SYSO on outcome did not
      significantly differ by individual arterial location (P for contrast=0.21).
      CONCLUSIONS: Approximately 60% of patients with acute ischemic stroke had SYSO,
      and the severity and number were inversely correlated with outcome. The results
      suggest that SYSO could predict stroke outcome.

PMID- 24741564
TI  - Serum 25-hydroxyvitamin d deficiency in ischemic stroke and subtypes in Indian
      patients.
AB  - BACKGROUND AND PURPOSE: Vitamin D deficiency is common across all age groups and
      may contribute to cardiovascular diseases. Serum 25-hydroxyvitamin D deficiency
      causing ischemic stroke has been documented in recent reports. AIM: To
      investigate the association of serum 25-hydroxyvitamin D deficiency with ischemic
      stroke and subtypes. METHODS: We recruited 250 consecutive ischemic stroke
      patients and 250 age and sex matched controls attending the Department of
      Neurology, at Yashoda hospital, Hyderabad, India, from January 2011 to December
      2012. All ischemic stroke patients underwent stroke subtyping. We measured 25
      hydroxyvitamin D by chemiluminescence test, serum calcium, phosphorus, alkaline
      phosphatase, and C-reactive protein (CRP) in cases and controls. RESULTS: Out of
      250 stroke patients, 190 (76%) were men and mean age was 58.4+/-11.1 years (age
      range-26-89 years). 25-hydroxyvitamin D deficiency was observed in 122 (48.8%)
      stroke patients and 79 (31.6%) controls (P=0.001). Among stroke patients, serum
      25-hydroxyvitamin D deficiency was found in 54.9% (50/91) of patients with large
      artery atherosclerosis, 54% (20/37) in cardioembolic stroke, 44.4% (20/45) in
      small artery diseases, 42.8% (15/35) in stroke of other determined etiology and
      40.4% (17/42) in stroke of un-determined etiology. Multiple logistic regression
      analysis showed an independent association of 25-hydroxyvitamin D deficiency with
      ischemic stroke (odds ratio: 1.6; 95% CI 1.2-2.8). The association was strongest
      with large artery atherosclerosis (odds ratio: 2.4; 95% CI 1.6-3.5) and
      cardioembolic stroke (odds ratio: 2.0; 95% CI 1.0-3.2). CONCLUSIONS: We found
      that 25-hydroxyvitamin D deficiency had an independent association with ischemic
      stroke. The association was established in large artery arthrosclerosis and
      cardioembolic stroke.

PMID- 24741565
TI  - A case of delayed neurological recovery with luxury perfusion and a high
      intracranial arterial calcification burden.

PMID- 24741567
TI  - Association of CHMP4B and autophagy with micronuclei: implications for cataract
      formation.
AB  - Autophagy is a mechanism of cellular self-degradation that is very important for
      cellular homeostasis and differentiation. Components of the endosomal sorting
      complex required for transport (ESCRT) machinery are required for endosomal
      sorting and also for autophagy and the completion of cytokinesis. Here we show
      that the ESCRT-III subunit CHMP4B not only localizes to normal cytokinetic
      bridges but also to chromosome bridges and micronuclei, the latter surrounded by
      lysosomes and autophagosomes. Moreover, CHMP4B can be co-immunoprecipitated with
      chromatin. Interestingly, a CHMP4B mutation associated with autosomal dominant
      posterior polar cataract abolishes the ability of CHMP4B to localize to
      micronuclei. We propose that CHMP4B, through its association with chromatin, may
      participate in the autophagolysosomal degradation of micronuclei and other
      extranuclear chromatin. This may have implications for DNA degradation during
      lens cell differentiation, thus potentially protecting lens cells from cataract
      development. 

PMID- 24741566
TI  - Genetic variants in the genes of the stress hormone signalling pathway and
      depressive symptoms during and after pregnancy.
AB  - PURPOSE: The aim of this study was to investigate whether single nucleotide
      polymorphisms (SNPs) in genes of the stress hormone signaling pathway,
      specifically FKBP5, NR3C1, and CRHR1, are associated with depressive symptoms
      during and after pregnancy. METHODS: The Franconian Maternal Health Evaluation
      Study (FRAMES) recruited healthy pregnant women prospectively for the assessment
      of maternal and fetal health including the assessment of depressiveness. The
      German version of the 10-item Edinburgh Postnatal Depression Scale (EPDS) was
      completed at three time points in this prospective cohort study. Visit 1 was at
      study entry in the third trimester of the pregnancy, visit 2 was shortly after
      birth, and visit 3 was 6-8 months after birth. Germline DNA was collected from
      361 pregnant women. Nine SNPs in the above mentioned genes were genotyped. After
      construction of haplotypes for each gene, a multifactorial linear mixed model was
      performed to analyse the depression values over time. RESULTS: EPDS values were
      within expected ranges and comparable to previously published studies. Neither
      did the depression scores differ for comparisons among haplotypes at fixed time
      points nor did the change over time differ among haplotypes for the examined
      genes. No haplotype showed significant associations with depressive symptoms
      severity during pregnancy or the postpartum period. CONCLUSION: The analysed
      candidate haplotypes in FKBP5, NR3C1, and CRHR1 did not show an association with
      depression scores as assessed by EPDS in this cohort of healthy unselected
      pregnant women.

PMID- 24741568
TI  - Visualization of genome signatures of eukaryote genomes by batch-learning self
      organizing map with a special emphasis on Drosophila genomes.
AB  - A strategy of evolutionary studies that can compare vast numbers of genome
      sequences is becoming increasingly important with the remarkable progress of high
      throughput DNA sequencing methods. We previously established a sequence alignment
      free clustering method "BLSOM" for di-, tri-, and tetranucleotide compositions in
      genome sequences, which can characterize sequence characteristics (genome
      signatures) of a wide range of species. In the present study, we generated BLSOMs
      for tetra- and pentanucleotide compositions in approximately one million sequence
      fragments derived from 101 eukaryotes, for which almost complete genome sequences
      were available. BLSOM recognized phylotype-specific characteristics (e.g., key
      combinations of oligonucleotide frequencies) in the genome sequences, permitting
      phylotype-specific clustering of the sequences without any information regarding
      the species. In our detailed examination of 12 Drosophila species, the
      correlation between their phylogenetic classification and the classification on
      the BLSOMs was observed to visualize oligonucleotides diagnostic for species
      specific clustering. 

PMID- 24741570
TI  - Combat diabetic nephropathy: from pathogenesis to treatment.

PMID- 24741569
TI  - Matrilin-2 is a widely distributed extracellular matrix protein and a potential
      biomarker in the early stage of osteoarthritis in articular cartilage.
AB  - In this study, we first generated and characterized a polyclonal antibody against
      unique domain of matrlin-2 and then used this specific antibody to assess the
      expression pattern of matrilin-2 by immunohistochemistry. We found that marilin-2
      is widely distributed in the connective tissues of many mouse tissues including
      heart, colon, penis, esophagus, lung, kidney, tracheal cartilage, developmental
      bone, and adult bone. The expression level of matrilin-2 was remarkably increased
      in the tissues of osteoarthritis developmental articular cartilage, compared to
      normal healthy tissues. Furthermore, we determined matrilin-2 expression in
      specific epithelial cells in stomach and ductal epithelial cells of salivary
      gland. In other tissues, the positive signals were mainly located around cardiac
      muscle cells and Purkinje fibers in the heart; corpus spongiosum in the penis;
      submucosa in the colon and esophagus; extracellular matrix of cartilage in the
      tracheal cartilage; and, glomerulus, the basement membrane of distal convoluted
      tubule and renal matrix in kidney. These observations indicated that the
      distribution pattern of matrilin-2 is heterogeneous in each tissue. Matrilin-2
      may play an important role in the communication of matrix to matrix and matrix to
      cells and will be used as a potential biomarker in the early stage of
      osteoarthritis of articular cartilage. 

PMID- 24741571
TI  - Ethnic differences in microRNA-375 expression level and DNA methylation status in
      type 2 diabetes of Han and Kazak populations.
AB  - Han population is six times as likely as Kazak population to present with type 2
      diabetes mellitus (T2DM) in China. We hypothesize that differential expression
      and CpG methylation of miR-375 may be an ethnic-related factor that influences
      the incidence of T2DM. The expression level of miR-375 was examined using real
      time PCR on Kazak and Han T2DM plasma samples. Furthermore, the methylation
      levels of CpG sites of miR-375 promoter were determined by MassARRAY Spectrometry
      in these samples. The relative expression levels of plasma miR-375 in Kazak T2DM
      samples are 1, and the relative expression levels of plasma miR-375 in Han T2DM
      samples are 3. The mean level of miR-375 methylation, calculated from the
      methylation levels of the CpG sites, was 8.47% for the Kazak T2DM group and
      10.38% for the Han T2DM group. Further, five CpG units showed a statistically
      significant difference between Kazak and Han T2DM samples, and, among them, four
      were hypomethylated and only one CpG unit showed hypermethylation in Kazak T2DM
      samples. These findings indicate that the expression levels of plasma miR-375 and
      its CpG methylation in the promoter region are ethnically different, which may
      contribute to the different incidence of diabetes observed in Kazak and Han
      populations. 

PMID- 24741572
TI  - Potential benefits of therapeutic use of beta2-adrenergic receptor agonists in
      neuroprotection and ParkinsonMUs disease.
AB  - The beta2-adrenergic receptor (beta2AR) is a seven-transmembrane (7TM) G-protein
      coupled receptor that is expressed on cells of the pulmonary, cardiac, skeletal
      muscle, and immune systems. Previous work has shown that stimulation of this
      receptor on immune cells has profound effects on the regulatory activity of both
      adaptive and innate immune cells. This review examines the functional dichotomy
      associated with stimulation of beta2AR and microglial cells. As well, recent
      studies targeting these receptors with long-acting agonists are considered with
      respect to their therapeutic potential in management of ParkinsonMUs disease.

PMID- 24741573
TI  - Interpretation of ANA indirect immunofluorescence test outside the darkroom using
      NOVA view compared to manual microscopy.
AB  - OBJECTIVE: To evaluate NOVA View with focus on reading archived images versus
      microscope based manual interpretation of ANA HEp-2 slides by an experienced,
      certified medical technologist. METHODS: 369 well defined sera from: 44
      rheumatoid arthritis, 50 systemic lupus erythematosus, 35 scleroderma, 19
      Sjogren's syndrome, and 10 polymyositis patients as well as 99 healthy controls
      were examined. In addition, 12 defined sera from the Centers for Disease Control
      and 100 random patient sera sent to ARUP Laboratories for ANA HEp-2 IIF testing
      were included. Samples were read using the archived images on NOVA View and
      compared to results obtained from manual reading. RESULTS: At a 1 : 40/1 : 80
      dilution the resulting comparison demonstrated 94.8%/92.9% positive, 97.4%/97.4%
      negative, and 96.5%/96.2% total agreements between manual IIF and NOVA View
      archived images. Agreement of identifiable patterns between methods was 97%, with
      PCNA and mixed patterns undetermined. CONCLUSION: Excellent agreements were
      obtained between reading archived images on NOVA View and manually on a
      fluorescent microscope. In addition, workflow benefits were observed which need
      to be analyzed in future studies.

PMID- 24741574
TI  - High prevalence of antinuclear antibodies in children with thyroid autoimmunity.
AB  - BACKGROUND: Antinuclear antibodies (ANA) are a hallmark of many autoimmune
      diseases and can be detected many years before disease onset. Autoimmune thyroid
      diseases (AITD) are frequently associated with other organ- and non-organ
      specific autoimmune disorders. Objectives. To assess the prevalence of ANA in
      pediatric patients with AITD and their clinical correlations. METHODS: Ninety
      three consecutive pediatric patients with AITD were enrolled (86 children with
      chronic lymphocytic thyroiditis and 7 with Graves' disease). ANA, anti-double DNA
      (anti-dsDNA) antibodies, anti-extractable nuclear antigen (anti-ENA), anti-cyclic
      citrullinated peptide antibodies (anti-CCP), and rheumatoid factor (RF) was
      obtained. Signs and symptoms potentially related to rheumatic diseases in
      children were investigated by a questionnaire. RESULTS: ANA positivity was found
      in 66/93 children (71%), anti-ENA in 4/93 (4.3%), anti-dsDNA in 1/93 (1.1%), RF
      in 3/93 (3.2%), and anti-CCP in none. No significant differences were found
      between the ANA-positive and ANA-negative groups with respect to age, sex, L
      thyroxine treatment, or prevalence of other autoimmune diseases. Overall,
      parental autoimmunity was found in 23%. CONCLUSIONS: ANA positivity was
      demonstrated in 71% of children with AITD. ANA positivity was not related to
      overt immune-rheumatic diseases. However, because the positivity of ANA can occur
      even many years before the onset of systemic autoimmune diseases, prospective
      studies are warranted.

PMID- 24741575
TI  - HLA-G dimers in the prolongation of kidney allograft survival.
AB  - Human leukocyte antigen-G (HLA-G) contributes to acceptance of allografts in
      solid organ/tissue transplantation. Most studies have determined that soluble HLA
      G isoforms are systematically detected in serum/plasma of transplanted patients
      with significantly fewer episodes of acute and/or chronic rejection of allogeneic
      tissue/organ. Current models of the interactions of HLA-G and its specific
      receptors explain it as functioning in a monomeric form. However, in recent
      years, new data has revealed the ability of HLA-G to form disulfide-linked
      dimeric complexes with high preferential binding and functional activities.
      Limited data are available on the role of soluble HLA-G dimers in clinical
      pathological conditions. We describe here the presence of soluble HLA-G dimers in
      kidney transplant patients. Our study showed that a high level of HLA-G dimers in
      plasma and increased expression of the membrane-bound form of HLA-G on monocytes
      are associated with prolongation of kidney allograft survival. We also determined
      that the presence of soluble HLA-G dimers links to the lower levels of
      proinflammatory cytokines, suggesting a potential role of HLA-G dimers in
      controlling the accompanying inflammatory state. 

PMID- 24741576
TI  - Obesity and cytokines in childhood-onset systemic lupus erythematosus.
AB  - BACKGROUND: In systemic lupus erythematosus (SLE), atherosclerosis is attributed
      to traditional and lupus related risk factors, including metabolic syndrome
      (MetS), obesity, and inflammation. Objective. To evaluate the association between
      obesity, measures of body fat content, serum tumor necrosis factor alpha (TNF
      alpha), and interleukin (IL)-6 and -10 levels in childhood-onset SLE (cSLE).
      METHODS: We screened consecutive cSLE patients followed up in the Pediatric
      Rheumatology Outpatient Clinic of the State University of Campinas. cSLE patients
      were assessed for disease and damage. Obesity was definite as body mass index
      (BMI) >=30 kg/m(2). Serum TNF-alpha, IL-6, and IL-10 levels were measured by
      ELISA. Dual-energy X-ray absorptiometry was used to determine total fat mass,
      lean mass, and percent of body fat. RESULTS: We included 52 cSLE patients and 52
      controls. cSLE patients had higher serum TNF-alpha  (P = 0.004), IL-6 (P =
      0.002), and IL-10 (P < 0.001) levels compared to controls. We observed higher
      serum TNF-alpha  (P = 0.036) levels in cSLE patients with obesity. An association
      between serum TNF-alpha levels and body fat percent (P = 0.046) and total fat
      mass on trunk region (P = 0.035) was observed. CONCLUSION: Serum TNF-alpha levels
      were associated with obesity and body fat content in cSLE. Our finding suggests
      that obesity may contribute to the increase of serum TNF-alpha levels in cSLE.

PMID- 24741578
TI  - Adoptive TIL transfer in the adjuvant setting for melanoma: long-term patient
      survival.
AB  - Two first analyses of our clinical trial on TIL as adjuvant therapy for melanoma
      were published in 2002 and 2007. We present here an update of the clinical
      results after a 17-year median followup. In this trial, disease-free patients
      were randomly assigned to receive either TIL/IL-2 or IL-2. The relapse-free
      survival (RFS) was the primary objective. Eighty-eight patients were enrolled. A
      new analysis performed in May 2013 did not show significant changes in RFS or OS
      duration. However, our first finding on the association between the number of
      invaded lymph nodes and TIL effectiveness was strengthened. The Cox model
      adjusted on this interaction showed for the first time a significant treatment
      effect when considering the overall population, both on the RFS and OS. Patients
      treated with TIL had a longer RFS (P = 0.023) or OS (P = 0.020). This study being
      with a very long followup (17 years), confirmed the association between TIL
      effectiveness and the number of invaded lymph nodes, indicating that a low tumor
      burden could be a crucial factor enhancing the curative effect of TIL in possible
      microscopic residual disease. Moreover, we confirmed that a prolonged survival
      was associated with the presence of specific TIL and a decrease in Foxp3
      expression. 

PMID- 24741577
TI  - Roles of the chemokine system in development of obesity, insulin resistance, and
      cardiovascular disease.
AB  - The escalating epidemic of obesity has increased the incidence of obesity-induced
      complications to historically high levels. Adipose tissue is a dynamic energy
      depot, which stores energy and mobilizes it during nutrient deficiency. Excess
      nutrient intake resulting in adipose tissue expansion triggers lipid release and
      aberrant adipokine, cytokine and chemokine production, and signaling that
      ultimately lead to adipose tissue inflammation, a hallmark of obesity. This low
      grade chronic inflammation is thought to link obesity to insulin resistance and
      the associated comorbidities of metabolic syndrome such as dyslipidemia and
      hypertension, which increase risk of type 2 diabetes and cardiovascular disease.
      In this review, we focus on and discuss members of the chemokine system for which
      there is clear evidence of participation in the development of obesity and
      obesity-induced pathologies. 

PMID- 24741579
TI  - Optimization of unnicked beta2-glycoprotein I and high avidity anti-beta2
      glycoprotein I antibodies isolation.
AB  - Patient biological material for isolation of beta2-glycoprotein I (beta2GPI) and
      high avidity IgG anti-beta2-glycoprotein I antibodies (HAv anti-beta2GPI)
      dictates its full utilization. The aim of our study was to evaluate/improve
      procedures for isolation of unnicked beta2GPI and HAv abeta2GPI to gain
      unmodified proteins in higher yields/purity. Isolation of beta2GPI from plasma
      was a stepwise procedure combining nonspecific and specific methods. For
      isolation of polyclonal HAv abeta2GPI affinity chromatographies with immobilized
      protein G and human beta2GPI were used. The unknown protein found during
      isolation was identified by liquid chromatography electrospray ionization mass
      spectrometry and the nonredundant National Center for Biotechnology Information
      database. The average mass of the isolated unnicked purified beta2GPI increased
      from 6.56 mg to 9.94 mg. In the optimized isolation procedure the high molecular
      weight protein (proteoglycan 4) was successfully separated from beta2GPI in the
      1st peaks with size exclusion chromatography. The average efficiency of the
      isolation procedure for polyclonal HAv anti-beta2GPI from different matrixes was
      13.8%, as determined by our in-house anti-beta2GPI ELISA. We modified the in
      house isolation and purification procedures of unnicked beta2GPI and HAv anti
      beta2GPI, improving the purity of antigen and antibodies as well as increasing
      the number of tests routinely performed with the in-house ELISA by ~50%.

PMID- 24741581
TI  - Peptide-based immunotherapeutics and vaccines.

PMID- 24741580
TI  - Revisiting the molecular mechanism of neurological manifestations in
      antiphospholipid syndrome: beyond vascular damage.
AB  - Antiphospholipid syndrome (APS) is a multiorgan disease often affecting the
      central nervous system (CNS). Typically, neurological manifestations of APS
      include thrombosis of cerebral vessels leading to stroke and requiring prompt
      initiation of treatment with antiplatelet drugs or anticoagulant therapy. In
      these cases, alterations of the coagulation system at various levels caused by
      multiple effects of antiphospholipid antibodies (aPL) have been postulated to
      explain the vascular damage to the CNS in APS. However, several nonvascular
      neurological manifestations of APS have progressively emerged over the past
      years. Nonthrombotic, immune-mediated mechanisms altering physiological basal
      ganglia function have been recently suggested to play a central role in the
      pathogenesis of these manifestations that include, among others, movement
      disorders such as chorea and behavioral and cognitive alterations. Similar
      clinical manifestations have been described in other autoimmune CNS diseases such
      as anti-NMDAR and anti-VGCK encephalitis, suggesting that the spectrum of immune
      mediated basal ganglia disorders is expanding, possibly sharing some
      pathophysiological mechanisms. In this review, we will focus on thrombotic and
      nonthrombotic neurological manifestations of APS with particular attention to
      immune-mediated actions of aPL on the vascular system and the basal ganglia. 

PMID- 24741582
TI  - Fcgamma-receptor IIIA polymorphism p.158F has no negative predictive impact on
      rituximab therapy with and without sequential chemotherapy in CD20-positive
      posttransplant lymphoproliferative disorder.
AB  - We retrospectively analyzed the p.V158F polymorphism of Fcgamma-receptor IIIA
      (FCGR3A, CD16) in patients with PTLD treated with rituximab monotherapy. Previous
      reports had indicated that the lower affinity F allele affects rituximab-mediated
      antibody-dependent cellular cytotoxicity (ADCC) and is linked to inferior outcome
      of rituximab monotherapy in B cell malignancies. 25 patients with PTLD after
      solid organ transplantation were included in this analysis. They had received 4
      weekly doses of rituximab as part of two clinical trials, which had a rituximab
      monotherapy induction regimen in common. 16/25 patients received further
      treatment with CHOP-21 after rituximab monotherapy (PTLD-1, NCT01458548). The
      FCGR3A status was correlated to the response after 4 cycles of rituximab
      monotherapy. Response to rituximab monotherapy was not affected by F carrier
      status. This is in contrast to previous findings in B cell malignancies where
      investigators found a predictive impact of FCGR3A status on outcome to rituximab
      monotherapy. One explanation for this finding could be that ADCC is impaired in
      transplant recipients receiving immunosuppression. These results suggest that
      carrying a FCRG3A F allele does not negatively affect rituximab therapy in
      immunosuppressed patients.

PMID- 24741583
TI  - Anti-MDA5 antibodies in a large Mediterranean population of adults with
      dermatomyositis.
AB  - A new myositis-specific autoantibody directed against melanoma differentiation
      associated gene 5 (anti-MDA5) has been described in patients with dermatomyositis
      (DM). We report the clinical characteristics of patients with anti-MDA5 in a
      large Mediterranean cohort of DM patients from a single center, and analyze the
      feasibility of detecting this autoantibody in patient sera using new assays with
      commercially available recombinant MDA5. The study included 117 white adult
      patients with DM, 15 (13%) of them classified as clinically amyopathic
      dermatomyositis (CADM). Clinical manifestations were analyzed, with special focus
      on interstitial lung disease and its severity. Determination of anti-MDA5
      antibodies was performed by a new ELISA and immunoblot technique. In sera, from
      14 (12%) DM patients (8 CADM), MDA5 was recognized by ELISA, and confirmed by
      immunoblot. Eight of the 14 anti-MDA5-positive patients (57.14%) presented
      rapidly-progressive interstitial lung disease (RP-ILD) versus 3 of 103 anti-MDA5
      negative patients (2.91%) (P < 0.05; OR: 44.4, 95% CI 9.3-212). The cumulative
      survival rate was significantly lower in anti-MDA5-positive patients than in the
      remainder of the series (P < 0.05). Patients with anti-MDA5-associated ILD
      presented significantly lower 70-month cumulative survival than antisynthetase
      associated ILD patients. Among the cutaneous manifestations, only panniculitis
      was significantly associated with the presence of anti-MDA5 antibodies (P < 0.05;
      OR: 3.85, 95% CI 1.11-13.27). These findings support the reliability of using
      commercially available recombinant MDA5 for detecting anti-MDA5 antibodies and
      confirm the association of these antibodies with RP-ILD in a large series of
      Mediterranean patients with DM. 

PMID- 24741584
TI  - Galphas protein expression is an independent predictor of recurrence in prostate
      cancer.
AB  - BACKGROUND: T393C polymorphism in the gene GNAS1, which encodes the G-protein
      alpha s subunit (Galphas) of heterotrimeric G protein, is significantly
      associated with the clinical outcome of patients suffering from several cancers.
      However, studies on the role and protein expression of Galphas subunit in
      prostate cancer were still unavailable. METHODS: The immunohistochemical staining
      was used to assess Galphas expression through tissue microarray procedure of 56
      metastatic PCas, 291 localized PCas, and 67 benign hyperplasia (BPH). Galphas
      expression was semiquantitatively scored and evaluated the correlation with
      pathologic parameters and biochemical recurrence of prostate-specific antigen
      (PSA). RESULTS: Galphas expression was localized in nuclear and cytoplasm in
      prostate cancer cells and downregulated in metastatic PCa compared to localized
      PCa and BPH (P < 0.001). Galphas was inversely associated with PSA level and
      Gleason scores; patients with low expression of Galphas had adverse
      clincopathological features. In multivariable Cox regression analysis, high
      Galphas expression and Gleason scores were independent predictors of both PSA
      progression-free and overall survival. CONCLUSIONS: Galphas down-expression is
      associated with adverse pathologic features and clinical PSA biochemical
      recurrence of prostate cancer. Galphas is an independent predictor to help
      determine the risk of PSA progression and death.

PMID- 24741585
TI  - Fusion-expressed CTB improves both systemic and mucosal T-cell responses elicited
      by an intranasal DNA priming/intramuscular recombinant vaccinia boosting regimen.
AB  - Previous study showed that CTB (Cholera toxin subunit B) can be used as a genetic
      adjuvant to enhance the systemic immune responses. To further investigate whether
      it can also be used as a genetic adjuvant to improve mucosal immune responses, we
      constructed DNA and recombinant Tiantan vaccinia (rTTV) vaccines expressing OVA
      CTB fusion antigen. Female C57BL/6 mice were immunized with an intranasal DNA
      priming/intramuscular rTTV boosting regimen. OVA specific T-cell responses were
      measured by IFN-gamma ELISPOT and specific antibody responses were determined by
      ELISA. Compared to the nonadjuvant group (pSV-OVA intranasal priming/rTTV-OVA
      intramuscular boosting), pSV-OVA-CTB intranasal priming/rTTV-OVA-CTB
      intramuscular boosting group significantly improved the magnitudes of T-cell
      responses at spleen (1562 +/- 567 SFCs/10(6) splenocytes versus 330 +/- 182
      SFCs/10(6) splenocytes, P < 0.01), mesenteric LN (96 +/- 83 SFCs/10(6)
      lymphocytes versus 1 +/- 2 SFCs/10(6) lymphocytes, P < 0.05), draining LNs of
      respiratory tract (109 +/- 60 SFCs/10(6) lymphocytes versus 2 +/- 2 SFCs/10(6)
      lymphocytes, P < 0.01) and female genital tract (89 +/- 48 SFCs/10(6) lymphocytes
      versus 23 +/- 21 SFCs/10(6) lymphocytes, P < 0.01). These results collectively
      demonstrated that fusion-expressed CTB could act as a potent adjuvant to improve
      both systemic and mucosal T-cell responses.

PMID- 24741586
TI  - Human adipose tissue macrophages are enhanced but changed to an anti-inflammatory
      profile in obesity.
AB  - OBJECTIVE: Adipose tissue (AT) macrophages are increased in obesity and
      associated with low grade inflammation. We aimed to characterize the phenotype of
      AT macrophages in humans in relation to obesity and insulin resistance. DESIGN:
      Gene-expression levels of general macrophage markers (CD68 and CD14),
      proinflammatory markers/M1 (TNF-alpha, MCP-1, and IL-6), and anti-inflammatory
      markers/M2 (CD163, CD206, and IL-10) were determined by RT-PCR in subcutaneous AT
      samples from lean and obese subjects. Insulin resistance was determined by HOMA
      IR. RESULTS: All the macrophage markers were elevated in the AT from obese
      compared to lean subjects (P < 0.001). To determine the phenotype of the
      macrophages the level of CD14 was used to adjust the total number of macrophages.
      The relative expression of CD163 and IL-10 was elevated, and TNF-alpha and IL-6
      were reduced in AT from obese subjects (all P < 0.05). In a multivariate
      regression analysis CD163 was the only macrophage marker significantly associated
      with HOMA-IR (beta : 0.57; P < 0.05). CONCLUSION: Obesity is associated with
      elevated numbers of macrophages in the AT. Unexpectedly, the macrophages change
      phenotype by obesity, with a preponderance of M2 and a decrement of M1 markers in
      AT from obese subjects. Moreover, CD163 was the only macrophage marker associated
      with HOMA-IR after multiple adjustments.

PMID- 24741587
TI  - The robust and modulated biomarker network elicited by the Plasmodium vivax
      infection is mainly mediated by the IL-6/IL-10 axis and is associated with the
      parasite load.
AB  - BACKGROUND: Recent studies have shown that the inflammatory process, including
      the biomarker production, and the intense activation of innate immune responses
      are greater in the malaria caused by Plasmodium vivax than other species. Here,
      we examined the levels of serum biomarkers and their interaction during acute
      malaria. MATERIAL AND METHODS: Blood samples were collected from P. vivax
      infected patients at admission and from healthy donors. Levels of serum
      biomarkers were measured by Cytometric Bead Assay or ELISA. RESULTS: P. vivax
      infection triggered the production of both inflammatory and regulatory
      biomarkers. Levels of IL-6, CXCL-8, IFN-gamma, IL-5, and IL-10 were higher in P.
      vivax-infected patients than in healthy donors. On the other hand, malaria
      patients produced lower levels of TNF-alpha, IL-12p70, and IL-2 than healthy
      individuals. While the levels of IL-10 and IL-6 were found independent on the
      number of malaria episodes, higher levels of these cytokines were seen in
      patients with higher parasite load. CONCLUSION: A mixed pattern of
      proinflammatory and regulatory biomarkers is produced in P. vivax malaria.
      Analysis of biomarker network suggests that IL-10 and IL-6 are a robust axis in
      malaria patients and that this interaction seems to be associated with the
      parasite load.

PMID- 24741588
TI  - Acquired hemophilia A: a frequently overlooked autoimmune hemorrhagic disorder.
AB  - Acquired hemophilia A (AHA) is a rare hemorrhagic disease in which autoantibodies
      against coagulation factor VIII- (FVIII-) neutralizing antibodies (inhibitors)
      impair the intrinsic coagulation system. As the inhibitors developed in AHA are
      autoantibodies, the disease may have an autoimmune cause and is often associated
      with autoimmune disease. Although acute hemorrhage associated with AHA may be
      fatal and is costly to treat, AHA is often unrecognized or misdiagnosed. AHA
      should thus be considered in the differential diagnosis particularly in
      postpartum women and the elderly with bleeding tendency or prolonged activated
      partial thromboplastin time. Cross-mixing tests and measurement of FVIII-binding
      antibodies are useful to confirm AHA diagnosis. For treatment of acute
      hemorrhage, hemostatic therapy with bypassing agents should be provided. Unlike
      in congenital hemophilia A with inhibitors, in which immune tolerance induction
      therapy using repetitive infusions of high-dose FVIII concentrates is effective
      for inhibitor eradication, immune tolerance induction therapy has shown poor
      efficacy in treating AHA. Immunosuppressive treatment should thus be initiated to
      eradicate inhibitors as soon as the diagnosis of AHA is confirmed. 

PMID- 24741589
TI  - Antibodies to Lactobacilli and Bifidobacteria in young children with different
      propensity to develop islet autoimmunity.
AB  - The intestinal microbiota is essential to the maturation and homeostasis of the
      immune system. Immunoblot assays were used to establish the prevalence of serum
      IgG, IgM, and IgA antibodies specific for Bifidobacterium adolescentis,
      Bifidobacterium longum, and Lactobacillus rhamnosus GG proteins in young children
      presenting with or without type 1 diabetes (T1D). We demonstrated that children
      between the ages of 6 and 12 months had a substantial increase in the frequency
      of IgG antibodies specific for L. rhamnosus GG proteins. We measured IgG, IgM,
      and IgA class antibody reactivity against B. adolescentis DSM 20083, B.
      adolescentis DSM 20086, and B. longum DSM 20088 proteins demonstrating
      significantly higher IgA responses against B. adolescentis DSM 20083 strain
      proteins in children who developed islet autoimmunity and T1D later in life. B.
      adolescentis strains showed more IgM type antibodies in children who developed
      T1D later in life, but the difference was not statistically significant. B.
      longum proteins were recognized by IgG and IgA antibodies to a higher extent
      compared to other bacteria studied. These results confirm that differences in
      immune reactivity against some commensal strains in young children may represent
      a different risk factor for developing T1D. 

PMID- 24741590
TI  - Anti-CD3 antibody treatment induces hypoglycemia and super tolerance to glucose
      challenge in mice through enhancing glucose consumption by activated lymphocytes.
AB  - Anti-CD3 antibody has been employed for various immune-mediated disorders.
      However, whether anti-CD3 administration leads to rapid metabolic alternation has
      not been well investigated. In the current study, we studied how anti-CD3
      treatment affected blood glucose levels in mice. We found that anti-CD3 treatment
      induced immediate reduction of blood glucose after administration. Furthermore, a
      single dose of anti-CD3 treatment corrected hyperglycemia in all nonobese
      diabetic mice with recently diagnosed diabetes. This glucose-lowering effect was
      not attributable to major T cell produced cytokines. Of interest, when tested in
      a normal strain of mice (C57BL/6), the serum levels of C-peptide in anti-CD3
      treated animals were significantly lower than control mice. Paradoxically, anti
      CD3 treated animals were highly tolerant to exogenous glucose challenge.
      Additionally, we found that anti-CD3 treatment significantly induced activation
      of T and B cells in vitro and in vivo. Further studies demonstrated that anti-CD3
      treatment lowered the glucose levels in T cell culture media and increased the
      intracellular transportation of 2-(N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino)-2
      deoxyglucose (2-NBDG) particularly in activated T and B cells. In addition,
      injection of anti-CD3 antibodies induced enhanced levels of Glut1 expression in
      spleen cells. This study suggests that anti-CD3 therapy-induced hypoglycemia
      likely results from increased glucose transportation and consumption by the
      activated lymphocytes. 

PMID- 24741592
TI  - Analytical and clinical comparison of two fully automated immunoassay systems for
      the diagnosis of celiac disease.
AB  - OBJECTIVE: Here we compared analytical and clinical performance characteristics
      of two novel automated assay systems for the detection of celiac disease (CD)
      specific antibodies: QUANTA Flash (INOVA Diagnostics, Inc.) and EliA (Thermo
      Scientific). METHODS: A total of 74 biopsy-proven CD patients (2 with IgA
      deficiency) and 138 controls were tested by both methods. RESULTS: Sensitivities
      of QUANTA Flash assays ranged from 35.1% to 90.5% and specificities from 96.4% to
      99.3%, while sensitivities for EliA assays ranged from 37.8% to 90.5% (equivocal
      considered positive) and specificities from 97.1% to 100.0%. Good qualitative
      agreement was found between all assays. Thirty-four (50.0%) of the 68 QUANTA
      Flash h-tTG IgA positive results were higher than 10 times the upper limit of
      normal (ULN). In contrast, only 22.8% of the EliA tTG IgA positive samples were
      >10x ULN. Seventy-three (98.6%) biopsy-proven CD patients were correctly
      identified with the QUANTA Flash h-tTG IgA+DGP IgG combination, while 64 (86.5%)
      and 72 (97.3%) (depending on equivocal range) were identified with the same
      combination of EliA assays. CONCLUSION: The QUANTA Flash CD assays have
      outstanding clinical performance. Of particular clinical significance, in light
      of proposals to decrease the absolute necessity of biopsy, was the demonstration
      that 50% of the QUANTA Flash h-tTG IgA results were >10x ULN.

PMID- 24741591
TI  - Adipokines, metabolic syndrome and rheumatic diseases.
AB  - The metabolic syndrome (MetS) is a cluster of cardiometabolic disorders that
      result from the increasing prevalence of obesity. The major components of MetS
      include insulin resistance, central obesity, dyslipidemia, and hypertension. MetS
      identifies the central obesity with increased risk for cardiovascular diseases
      (CVDs) and type-2 diabetes mellitus (T2DM). Patients with rheumatic diseases,
      such as rheumatoid arthritis, osteoarthritis, systemic lupus erythematosus, and
      ankylosing spondylitis, have increased prevalence of CVDs. Moreover, CVD risk is
      increased when obesity is present in these patients. However, traditional
      cardiovascular risk factors do not completely explain the enhanced cardiovascular
      risk in this population. Thus, MetS and the altered secretion patterns of
      proinflammatory adipokines present in obesity could be the link between CVDs and
      rheumatic diseases. Furthermore, adipokines have been linked to the pathogenesis
      of MetS and its comorbidities through their effects on vascular function and
      inflammation. In the present paper, we review recent evidence of the role played
      by adipokines in the modulation of MetS in the general population, and in
      patients with rheumatic diseases. 

PMID- 24741593
TI  - The mosaic of "seronegative" antiphospholipid syndrome.
AB  - In the clinical practice it is possible to find patients with clinical signs
      suggestive of antiphospholipid syndrome (APS), who are persistently negative for
      the laboratory criteria of APS, that is, anti-cardiolipin antibodies (aCL), anti
      beta2-GPI antibodies and lupus anticoagulant. Therefore, it was proposed for
      these cases the term of seronegative APS (SN-APS). In order to detect
      autoantibodies with different methodological approaches, sera from 24 patients
      with SN-APS were analysed for anti-phospholipid antibodies using TLC
      immunostaining, for anti-vimentin/cardiolipin antibodies by enzyme-linked
      immunosorbent assay (ELISA), and for anti-annexin V and anti-prothrombin
      antibodies by ELISA and dot blot. Control groups of our study were 25 patients
      with APS, 18 with systemic lupus erythematosus (SLE), and 32 healthy controls.
      Results revealed that 13/24 (54.2%) SN-APS sera were positive for aCL (9 of whom
      were also positive for lysobisphosphatidic acid) by TLC immunostaining, 11/24
      (45.8%) for anti-vimentin/cardiolipin antibodies, 3/24 (12.5%) for anti
      prothrombin antibodies, and 1/24 (4.2%) for anti-annexin V antibodies. These
      findings suggest that in sera from patients with SN-APS, antibodies may be
      detected using "new" antigenic targets (mainly vimentin/cardiolipin) or
      methodological approaches different from traditional techniques (mainly TLC
      immunostaining). Thus, SN-APS represents a mosaic, in which antibodies against
      different antigenic targets may be detected.

PMID- 24741594
TI  - Construction of a chimeric secretory IgA and its neutralization activity against
      avian influenza virus H5N1.
AB  - Secretory immunoglobulin A (SIgA) acts as the first line of defense against
      respiratory pathogens. In this assay, the variable regions of heavy chain (VH)
      and Light chain (VL) genes from a mouse monoclonal antibody against H5N1 were
      cloned and fused with human IgA constant regions. The full-length chimeric light
      and heavy chains were inserted into a eukaryotic expressing vector and then
      transfected into CHO/dhfr-cells. The chimeric monomeric IgA antibody expression
      was confirmed by using ELISA, SDS-PAGE, and Western blot. In order to obtain a
      dimeric secretory IgA, another two expressing plasmids, namely, pcDNA4/His A-IgJ
      and pcDNA4/His A-SC, were cotransfected into the CHO/dhfr-cells. The expression
      of dimeric SIgA was confirmed by using ELISA assay and native gel
      electrophoresis. In microneutralization assay on 96-well immunoplate, the
      chimeric SIgA showed neutralization activity against H5N1 virus on MDCK cells and
      the titer was determined to be 1 : 64. On preadministrating intranasally, the
      chimeric SIgA could prevent mice from lethal attack by using A/Vietnam/1194/04
      H5N1 with a survival rate of 80%. So we concluded that the constructed
      recombinant chimeric SIgA has a neutralization capability targeting avian
      influenza virus H5N1 infection in vitro and in vivo. 

PMID- 24741595
TI  - A Mycobacterium bovis BCG-naked DNA prime-boost vaccination strategy induced CD4+
      and CD8+ T-cell response against Mycobacterium tuberculosis immunogens.
AB  - Mycobacterium tuberculosis infection is still a major global public health
      problem. Presently the only tuberculosis (TB) vaccine available is Bacille
      Calmette-Guerin (BCG), although it fails to adequately protect against pulmonary
      TB in adults. To solve this problem, the development of a new effective vaccine
      is urgently desired. BCG-prime DNA-booster vaccinations strategy has been shown
      to induce greater protection against tuberculosis (TB) than BCG alone. Some
      studies have demonstrated that the two genes (Rv1769 and Rv1772) are excellent T
      cell antigens and could induce T-cell immune responses. In this research, we
      built BCG-C or BCG-P prime-recombination plasmid PcDNA3.1-Rv1769 or PcDNA3.1
      Rv1772 boost vaccinations strategy to immunize BALB/c mice and evaluated its
      immunogenicity. The data suggests that the BCG-C+3.1-72 strategy could elicit the
      most long-lasting and strongest Th1-type cellular immune responses and the BCG
      C+3.1-69 strategy could induce the high level CD8+ T-cell response at certain
      time points. These findings support the ideas that the prime-boost strategy as a
      combination of vaccines may be better than a single vaccine for protection
      against tuberculosis. 

PMID- 24741596
TI  - Anti-nuclear antibodies in daily clinical practice: prevalence in primary,
      secondary, and tertiary care.
AB  - For the diagnosis of systemic autoimmune rheumatic diseases (SARD), patients are
      screened for anti-nuclear antibodies (ANA). ANA, as assessed by indirect
      immunofluorescence (IIF), have a poor specificity. This hampers interpretation of
      positive results in clinical settings with low pretest probability of SARD. We
      hypothesized that the utility of positive ANA IIF results increases from primary
      to tertiary care. We retrospectively determined ANA, anti-ENA, and anti-dsDNA
      antibody prevalence in patient cohorts from primary (n = 1453), secondary (n =
      1621), and tertiary (n = 1168) care settings. Results reveal that from primary
      care to tertiary care, ANA prevalence increases (6.2, 10.8, and 16.0%, resp.).
      Moreover, in primary care low titres (70% versus 51% and 52% in secondary and
      tertiary care, resp.) are more frequent and anti-ENA/dsDNA reactivities are less
      prevalent (21% versus 39% in secondary care). Typically, in tertiary care the
      prevalence of anti-ENA/dsDNA reactivities (21%) is lower than expected. From this
      descriptive study we conclude that positive ANA IIF results are more prone to
      false interpretation in clinical settings with low pretest probabilities for
      SARD, as in primary care. Whether alternative approaches, that is,
      immunoadsorption of anti-DFS70 antibodies or implementation of anti-ENA screen
      assays, perform better, needs to be determined. 

PMID- 24741597
TI  - Sonic hedgehog signaling drives proliferation of synoviocytes in rheumatoid
      arthritis: a possible novel therapeutic target.
AB  - Sonic hedgehog (Shh) signaling controls many aspects of human development,
      regulates cell growth and differentiation in adult tissues, and is activated in a
      number of malignancies. Rheumatoid arthritis (RA) is characterized by chronic
      synovitis and pannus formation associated with activation of fibroblast-like
      synoviocytes (FLS). We investigated whether Shh signaling plays a role in the
      proliferation of FLS in RA. Expression of Shh signaling related components (Shh,
      Ptch1, Smo, and Gli1) in RA synovial tissues was examined by immunohistochemistry
      (IHC) and in FLS by IHC, immunofluorescence (IF), quantitative RT-PCR, and
      western blotting. Expression of Shh, Smo, and Gli1 in RA synovial tissue was
      higher than that in control tissue (P < 0.05). Cyclopamine (a specific inhibitor
      of Shh signaling) decreased mRNA expression of Shh, Ptch1, Smo, and Gli1 in
      cultured RA FLS, Shh, and Smo protein expression, and significantly decreased FLS
      proliferation. Flow cytometry analysis suggested that cyclopamine treatment
      resulted in cell cycle arrest of FLS in G1 phase. Our data show that Shh
      signaling is activated in synovium of RA patients in vivo and in cultured FLS
      form RA patients in vitro, suggesting a role in the proliferation of FLS in RA.
      It may therefore be a novel therapeutic target in RA. 

PMID- 24741598
TI  - Analysis of autoantibodies to 3-hydroxy-3-methylglutaryl-coenzyme A reductase
      using different technologies.
AB  - Diagnostic tests are needed to aid in the diagnosis of necrotizing myopathies
      associated with statin use. This study aimed to compare different technologies
      for the detection of anti-HMGCR antibodies and analyze the clinical phenotype and
      autoantibody profile of the patients. Twenty samples from myositis patients
      positive for anti-HMGCR antibodies using a research addressable laser bead assay
      and 20 negative controls were tested for autoantibodies to HMGCR: QUANTA Lite
      HMGCR ELISA and QUANTA Flash HMGCR CIA. All patients were also tested for
      antibodies to extractable nuclear antigens and myositis related antibodies. To
      verify the specificity of the ELISA, 824 controls were tested. All three assays
      showed qualitative agreements of 100% and levels of anti-HMGCR antibodies showed
      significant correlation: Spearman's rho > 0.8. The mean age of the anti-HMGCR
      antibody positive patients was 54.4 years, 16/20 were females, and 18/20 had
      necrotizing myopathy (two patients were not diagnosed). Nine out of 20 anti-HMGCR
      positive patients were on statin. All patients with anti-HMGCR antibodies were
      negative for all other autoantibodies tested. Testing various controls showed
      high specificity (99.3%). Anti-HMGCR antibodies are not always associated with
      the use of statin and appear to be the exclusive autoantibody specificity in
      patients with statin associated myopathies. 

PMID- 24741599
TI  - Infection and HLA-G molecules in nasal polyposis.
AB  - Sinonasal polyposis (SNP) is a chronic inflammatory pathology with an unclear
      aetiopathogenesis. Human papillomavirus (HPV) infection is one candidate for the
      development of SNP for its epithelial cell trophism, hyperproliferative effect,
      and the induction of immune-modulatory molecules as HLA-G. We enrolled 10
      patients with SNP without concomitant allergic diseases (SNP-WoAD), 10 patients
      with SNP and suffering from allergic diseases (SNP-WAD), and 10 control subjects
      who underwent rhinoplasty. We analyzed the presence of high- and low-risk HPV DNA
      and the expression of membrane HLA-G (mHLA-G) and IL-10 receptor (IL-10R) and of
      soluble HLA-G (sHLA-G) and IL-10 by polyp epithelial cells. The results showed
      the presence of HPV-11 in 50% of SNP-WoAD patients (OR:5.5), all characterized by
      a relapsing disease. HPV-11 infection was absent in nonrelapsing SNP-WoAD
      patients, in SNP-WAD patients and in controls, supporting the hypothesis that HPV
      11 increases risk of relapsing disease. HPV-11 positive SNP-WoAD patients
      presented with mHLA-G and IL-10R on epithelial cells from nasal polyps and showed
      secretion of sHLA-G and IL-10 in culture supernatants. No HLA-G expression was
      observed in HPV negative polyps. These data highlight new aspects of polyposis
      aetiopathogenesis and suggest HPV-11 and HLA-G/IL-10 presence as prognostic
      markers in the follow-up of SNP-WoAD. 

PMID- 24741600
TI  - The expression and clinical significance of different forms of Mer receptor
      tyrosine kinase in systemic lupus erythematosus.
AB  - OBJECTIVE: To investigate the expression and clinical significance of trans
      membrane MerTK (mMer) on circulating CD14+ monocytes/macrophages and soluble
      MerTK (sMer) levels in plasma in systemic lupus erythematosus (SLE). METHOD: 108
      SLE patients and 42 healthy controls were recruited in this study. The expression
      of mMer on the surfaces of CD14+ monocytes/macrophages was evaluated by flow
      cytometry (FCM). The sMer levels were measured by ELISA. Real-time quantitative
      PCR was applied to evaluate the mRNA levels of MerTK and ADAM17. RESULTS: Both
      mMer expression on CD14+ monocytes/macrophages and sMer levels in plasma
      significantly increased in SLE patients compared to healthy subjects. The
      frequency of anti-inflammatory MerTK expressing CD14+CD16+ monocytes decreased in
      SLE. mMer expression was positively correlated with CD163 expression on CD14+
      cells. Both the mMer expression on CD14+ monocytes/macrophages and sMer levels in
      plasma were positively correlated with SLEDAI. Furthermore, more elevated mMer
      and sMer levels were found in patients with higher SLEDAI, presence of anti-SSA,
      anti-Sm autoantibodies, and lupus nephritis. CONCLUSION: Both mMer and sMer
      levels significantly increased in SLE and positively correlated with disease
      activity and severity. The upregulation of MerTK expression may serve as a
      biomarker of the disease activity and severity of SLE.

PMID- 24741601
TI  - Is vestibular neuritis an immune related vestibular neuropathy inducing vertigo?
AB  - OBJECTIVES: To review the current knowledge of the aetiology of vestibular
      neuritis including viral infections, vascular occlusion, and immunomediated
      mechanisms and to discuss the pathogenesis with relevance to pharmacotherapy.
      SYSTEMATIC REVIEW METHODOLOGY: Relevant publications on the aetiology and
      treatment of vestibular neuritis from 1909 to 2013 were analysed. RESULTS AND
      CONCLUSIONS: Vestibular neuritis is the second most common cause of peripheral
      vestibular vertigo and is due to a sudden unilateral loss of vestibular function.
      Vestibular neuronitis is a disorder thought to represent the vestibular-nerve
      equivalent of sudden sensorineural hearing loss. Histopathological studies of
      patients who died from unrelated clinical problems have demonstrated degeneration
      of the superior vestibular nerve. The characteristic signs and symptoms include
      sudden and prolonged vertigo, the absence of auditory symptoms, and the absence
      of other neurological symptoms. The aetiology and pathogenesis of the condition
      remain unknown. Proposed theories of causation include viral infections, vascular
      occlusion, and immunomediated mechanisms. The management of vestibular neuritis
      involves symptomatic treatment with antivertiginous drugs, causal treatment with
      corticosteroids, and physical therapy. Antiviral agents did not improve the
      outcomes.

PMID- 24741602
TI  - Modulation of circulating cytokine-chemokine profile in patients affected by
      chronic venous insufficiency undergoing surgical hemodynamic correction.
AB  - The expression of proinflammatory cytokines/chemokines has been reported in in
      vitro/ex vivo settings of chronic venous insufficiency (CVI), but the
      identification of circulating mediators that might be associated with altered
      hemodynamic forces or might represent innovative biomarkers is still missing. In
      this study, the circulating levels of 31 cytokines/chemokines involved in
      inflammatory/angiogenic processes were analysed in (i) CVI patients at baseline
      before surgical hemody namic correction, (ii) healthy subjects, and (iii) CVI
      patients after surgery. In a subgroup of CVI patients, in whom the baseline
      levels of cytokines/chemokines were analyzed in paired blood samples obtained
      from varicose vein and forearm vein, EGF, PDGF, and RANTES were increased at the
      varicose vein site as compared to the general circulation. Moreover, while at
      baseline, CVI patients showed increased levels of 14 cytokines/chemokines as
      compared to healthy subjects, 6 months after surgery, 11 cytokines/chemokines
      levels were significantly reduced in the treated CVI patients as compared to the
      CVI patients before surgery. Of note, a patient who exhibited recurrence of the
      disease 6 months after surgery, showed higher levels of EGF, PDGF, and RANTES
      compared to nonrecurrent patients, highlighting the potential role of the
      EGF/PDGF/RANTES triad as sensitive biomarkers in the context of CVI. 

PMID- 24741603
TI  - Porphyromonas gingivalis: major periodontopathic pathogen overview.
AB  - Porphyromonas gingivalis is a Gram-negative oral anaerobe that is involved in the
      pathogenesis of periodontitis and is a member of more than 500 bacterial species
      that live in the oral cavity. This anaerobic bacterium is a natural member of the
      oral microbiome, yet it can become highly destructive (termed pathobiont) and
      proliferate to high cell numbers in periodontal lesions: this is attributed to
      its arsenal of specialized virulence factors. The purpose of this review is to
      provide an overview of one of the main periodontal pathogens-Porphyromonas
      gingivalis. This bacterium, along with Treponema denticola and Tannerella
      forsythia, constitute the "red complex," a prototype polybacterial pathogenic
      consortium in periodontitis. This review outlines Porphyromonas gingivalis
      structure, its metabolism, its ability to colonize the epithelial cells, and its
      influence upon the host immunity. 

PMID- 24741604
TI  - Cell transfer therapy for cancer: past, present, and future.
AB  - Cell transfer therapy for cancer has made a rapid progress recently and the
      immunotherapy has been recognized as the fourth anticancer modality after
      operation, chemotherapy, and radiotherapy. Lymphocytes used for cell transfer
      therapy include dendritic cells, natural killer (NK) cells, and T lymphocytes
      such as tumor-infiltrating lymphocytes (TILs) and cytotoxic T lymphocytes (CTLs).
      In vitro activated or engineered immune cells can traffic to cancer tissues to
      elicit persistent antitumor immune response which is very important especially
      after immunosuppressive treatments such as chemotherapy. In this review, we
      overviewed recent advances in the exploration of dendritic cells, NK cells, and T
      cells for the treatment of human cancer cells. 

PMID- 24741605
TI  - Insight into gene polymorphisms involved in toll-like receptor/interferon
      signalling pathways for systemic lupus erythematosus in South East Asia.
AB  - Polymorphisms in genes involved in toll-like receptor/interferon signalling
      pathways have been reported previously to be associated with SLE in many
      populations. This study aimed to investigate the role of seven single nucleotide
      polymorphisms within TNFAIP3, STAT4, and IRF5, which are involved in upstream and
      downstream pathways of type I interferon production, in SLE in the South East
      Asian populations. Genotyping of 360 Malaysian SLE patients and 430 normal
      healthy individuals revealed that minor alleles of STAT4 rs7574865 and rs10168266
      were associated with elevated risk of SLE in the Chinese and Malay patients,
      respectively (P = 0.028, odds ratio (OR) = 1.42; P = 0.035, OR = 1.80,
      respectively). Polymorphisms in TNFAIP3 and IRF5 did not show significant
      associations with SLE in any of the ethnicities. Combined analysis of the Malays,
      Chinese, and Indians for each SNP indicated that STAT4 rs10168266 was
      significantly associated with the Malaysian SLE as a whole (P = 0.014; OR =
      1.435). The meta-analysis of STAT4 rs10168266, which combined the data of other
      studies and this study, further confirmed its importance as the risk factor for
      SLE by having pooled OR of 1.559 and P value of <0.001. 

PMID- 24741606
TI  - Transplant glomerulopathy: the interaction of HLA antibodies and endothelium.
AB  - Transplant glomerulopathy (TG) is a major cause of chronic graft dysfunction
      without effective therapy. Although the histological definition of TG is well
      characterized, the pathophysiological pathways leading to TG development are
      still poorly understood. Electron microscopy suggests an earlier appearance of TG
      and suggests that endothelial cell injury is the first sign of the disease. The
      pathogenic role of human leukocyte antigen (HLA) antibodies in endothelial cells
      has been described in acute vascular and humoral rejection. However the
      mechanisms and pathways of endothelial cell injury by HLA antibodies remain
      unclear. Despite the description of different causes of the morphological lesion
      of TG (hepatitis, thrombotic microangiopathy), the strong link between TG and
      chronic antibody mediated rejection suggests a major role for HLA antibodies in
      TG formation. In this review, we describe the effect of classes I or II HLA
      antibodies in TG and especially the implication of donor specific antibodies
      (DSA). We update recent studies about endothelial cells and try to explain the
      different signals and intracellular pathways involved in the progression of TG. 

PMID- 24741607
TI  - Capillary dilation and rarefaction are correlated with intracapillary
      inflammation in antibody-mediated rejection.
AB  - Antibody-mediated rejection (ABMR) remains one of the major causes of graft loss
      after renal transplantation. It is dominated by endothelial damage in
      microcirculation. Clarifying the mechanism of microcirculating damage is
      obviously a key step to understand the pathogenesis of ABMR. Here we
      characterized capillary variation in ABMR and its possible mechanisms. Compared
      with T cell-mediated rejection and stable grafts, there was a significant
      dilation and rarefaction in peritubular capillaries (PTCs) of the ABMR group;
      Image-Pro Plus revealed a significantly larger intra-PTC area. Interestingly, the
      dilation of PTCs was strongly correlated with the intra-PTC cell counting.
      Moreover, peritubular capillary inflammation is correlated with in situ T-bet
      expression, and there was a good correlation between the intra-PTC expression of
      T-bet and the PTC diameter. HIF-1alpha up-regulation could be observed in ABMR
      but it was not necessary for capillary dilation. In general, ABMR is
      characterized with early capillary dilation and rarefaction; our data confirmed
      that the dilation is strongly correlated with intracapillary inflammation, which
      in turn is correlated with in situ T-bet expression. T-bet plays an important
      role in the development of microcirculating injury, and thus it is a potential
      target for the treatment of ABMR.

PMID- 24741608
TI  - The many faces of human leukocyte antigen-G: relevance to the fate of pregnancy.
AB  - Pregnancy is an immunological paradox, where fetal antigens encoded by
      polymorphic genes inherited from the father do not provoke a maternal immune
      response. The fetus is not rejected as it would be theorized according to
      principles of tissue transplantation. A major contribution to fetal tolerance is
      the human leukocyte antigen (HLA)-G, a nonclassical HLA protein displaying
      limited polymorphism, restricted tissue distribution, and a unique alternative
      splice pattern. HLA-G is primarily expressed in placenta and plays multifaceted
      roles during pregnancy, both as a soluble and a membrane-bound molecule. Its
      immunomodulatory functions involve interactions with different immune cells and
      possibly regulation of cell migration during placental development. Recent
      findings include HLA-G contributions from the father and the fetus itself. Much
      effort has been put into clarifying the role of HLA-G during pregnancy and
      pregnancy complications, such as preeclampsia, recurrent spontaneous abortions,
      and subfertility or infertility. This review aims to clarify the multifunctional
      role of HLA-G in pregnancy-related disorders by focusing on genetic variation,
      differences in mRNA stability between HLA-G alleles, differences in HLA-G isoform
      expression, and possible differences in functional activity. Furthermore, we
      highlight important observations regarding HLA-G genetics and expression in
      preeclampsia that future research should address. 

PMID- 24741609
TI  - Tumor-activated TCRgammadelta+ T cells from gastric cancer patients induce the
      antitumor immune response of TCRalphabeta+ T cells via their antigen-presenting
      cell-like effects.
AB  - Human gammadelta T cells display the principal characteristics of professional
      antigen-presenting cells (APCs), in addition to playing a vital role in immunity
      through cytokine secretion and their cytotoxic activity. However, it is not clear
      whether gammadelta T cells perform APC-like functions under pathological
      conditions. In this study, we showed that, in contrast to peripheral-derived
      gammadelta T cells directly isolated from PBMCs of gastric cancer patients, tumor
      activated gammadelta T cells not only killed tumor cells efficiently but also
      strongly induced primary CD4(+) and CD8(+) alphabeta T cells proliferation and
      differentiation. More importantly, they abrogated the immunosuppression induced
      by CD4(+)CD25(+) Treg cells and induced the cytotoxic function of CD8(+)
      alphabeta T cells from patients with gastric cancer. In conclusion, tumor
      activated gammadelta T cells can induce adaptive immune responses through their
      APC-like functions, and these cells may be a potentially useful tool in the
      development of tumor vaccines and immunotherapy.

PMID- 24741610
TI  - Anti-VEGF for the management of diabetic macular edema.
AB  - Diabetic retinopathy (DR) is an important cause of vision loss around the world,
      being the leading cause in the population between 20 and 60 years old. Among
      patients with DR, diabetic macular edema (DME) is the most frequent cause of
      vision impairment and represents a significant public health issue. Macular
      photocoagulation has been the standard treatment for this condition reducing the
      risk of moderate visual loss by approximately 50%. The role of vascular
      endothelial growth factor (VEGF) in DR and DME pathogenesis has been demonstrated
      in recent studies. This review addresses and summarizes data from the clinical
      trials that investigated anti-VEGF for the management of DME and evaluates their
      impact on clinical practice. The literature searches were conducted between
      August and October 2013 in PubMed and Cochrane Library with no date restrictions
      and went through the most relevant studies on pegaptanib, ranibizumab,
      bevacizumab, and aflibercept for the management of DME. The efficacy and safety
      of intravitreal anti-VEGF as therapy for DME have recently been proved by various
      clinical trials providing significantly positive visual and anatomical results.
      Regarding clinical practice, those outcomes have placed intravitreal injection of
      anti-VEGF as an option that must be considered for the treatment of DME. 

PMID- 24741611
TI  - Cell-mediated immunity and vaccines.

PMID- 24741612
TI  - HLA-G expression on blasts and tolerogenic cells in patients affected by acute
      myeloid leukemia.
AB  - Human Leukocyte Antigen-G (HLA-G) contributes to cancer cell immune escape from
      host antitumor responses. The clinical relevance of HLA-G in several malignancies
      has been reported. However, the role of HLA-G expression and functions in Acute
      Myeloid Leukemia (AML) is still controversial. Our group identified a subset of
      tolerogenic dendritic cells, DC-10 that express HLA-G and secrete IL-10. DC-10
      are present in the peripheral blood and are essential in promoting and
      maintaining tolerance via the induction of adaptive T regulatory (Treg) cells. We
      investigated HLA-G expression on blasts and the presence of HLA-G-expressing DC
      10 and CD4(+) T cells in the peripheral blood of AML patients at diagnosis.
      Moreover, we explored the possible influence of the 3' untranslated region
      (3'UTR) of HLA-G, which has been associated with HLA-G expression, on AML
      susceptibility. Results showed that HLA-G-expressing DC-10 and CD4(+) T cells are
      highly represented in AML patients with HLA-G positive blasts. None of the HLA-G
      variation sites evaluated was associated with AML susceptibility. This is the
      first report describing HLA-G-expressing DC-10 and CD4(+) T cells in AML
      patients, suggesting that they may represent a strategy by which leukemic cells
      escape the host's immune system. Further studies on larger populations are
      required to verify our findings. 

PMID- 24741613
TI  - Periodontitis as a risk factor of atherosclerosis.
AB  - Over the last two decades, the amount of evidence corroborating an association
      between dental plaque bacteria and coronary diseases that develop as a result of
      atherosclerosis has increased. These findings have brought a new aspect to the
      etiology of the disease. There are several mechanisms by which dental plaque
      bacteria may initiate or worsen atherosclerotic processes: activation of innate
      immunity, bacteremia related to dental treatment, and direct involvement of
      mediators activated by dental plaque and involvement of cytokines and heat shock
      proteins from dental plaque bacteria. There are common predisposing factors which
      influence both periodontitis and atherosclerosis. Both diseases can be initiated
      in early childhood, although the first symptoms may not appear until adulthood.
      The formation of lipid stripes has been reported in 10-year-old children and the
      increased prevalence of obesity in children and adolescents is a risk factor
      contributing to lipid stripes development. Endothelium damage caused by the
      formation of lipid stripes in early childhood may lead to bacteria penetrating
      into blood circulation after oral cavity procedures for children as well as for
      patients with aggressive and chronic periodontitis. 

PMID- 24741614
TI  - Genetic diversity of MSP1 Block 2 of Plasmodium vivax isolates from Manaus
      (central Brazilian Amazon).
AB  - The diversity of MSP1 in both Plasmodium falciparum and P. vivax is presumed be
      associated to parasite immune evasion. In this study, we assessed genetic
      diversity of the most variable domain of vaccine candidate N-terminal PvMSP1
      (Block 2) in field isolates of Manaus. Forty-seven blood samples the polymorphism
      of PvMSP1 Block 2 generates four fragment sizes. In twenty-eight of them,
      sequencing indicated seven haplotypes of PvMSP1 Block 2 circulating among field
      isolates. Evidence of striking exchanges was observed with two stretches flanking
      the repeat region and two predicted recombination sites were described. Single
      nucleotide polymorphisms determined with concurrent infections per patient
      indicated that nonsynonymous substitutions occurred preferentially in the repeat
      rich regions which also were predicted as B-cell epitopes. The comprehensive
      understanding of the genetic diversity of the promising Block 2 associated with
      clinical immunity and a reduced risk of infection by Plasmodium vivax would be
      important for the rationale of malaria vaccine designs. 

PMID- 24741615
TI  - Flow cytometric detection of p38 MAPK phosphorylation and intracellular cytokine
      expression in peripheral blood subpopulations from patients with autoimmune
      rheumatic diseases.
AB  - Flow cytometric analysis of p38 mitogen-activated protein kinase (p38 MAPK)
      signaling cascade is optimally achieved by methanol permeabilization protocols.
      Such protocols suffer from the difficulties to accurately detect intracellular
      cytokines and surface epitopes of infrequent cell subpopulations, which are
      removed by methanol. To overcome these limitations, we have modified methanol
      based phosphoflow protocols using several commercially available antibody clones
      suitable for surface antigens, intracellular cytokines, and p38 MAPK. These
      included markers of B cells (CD19, CD20, and CD22), T cells (CD3, CD4, and CD8),
      NK (CD56 and CD7), and dendritic cells (CD11c). We have also tested surface
      markers of costimulatory molecules, such as CD27. We have successfully determined
      simultaneous expression of IFN- gamma , as well as IL-10, and phosphorylated p38
      in cell subsets. The optimized phosphoflow protocol has also been successfully
      applied in peripheral blood mononuclear cells or purified cell subpopulations
      from patients with various autoimmune diseases. In conclusion, our refined
      phosphoflow cytometric approach allows simultaneous detection of p38 MAPK
      activity and intracellular cytokine expression and could be used as an important
      tool to study signaling cascades in autoimmunity. 

PMID- 24741616
TI  - Idiopathic non cirrhotic portal hypertension and spleno-portal axis abnormalities
      in patients with severe primary antibody deficiencies.
AB  - BACKGROUND AND AIM: Portal hypertension has been reported in association with
      acquired and primary immune deficiencies without a comprehensive description of
      associated spleno-portal axis abnormalities. Pathological mechanisms are poorly
      defined. METHODS: Observational, single centre study with the aim of assessing
      the prevalence of spleno-portal axis abnormalities in an unselected cohort of 123
      patients with primary antibody deficiencies and without known causes of liver
      diseases regularly followed up for a mean time of 18 +/- 14 years. A cumulative
      period of 1867 patients-year was analysed. Clinical and immunological data,
      abdominal ultrasounds, CT scans, and endoscopy features were included in the
      analysis. RESULTS: Twenty-five percent of patients with primary antibody
      deficiencies had signs of portal vein enlargement but only 4% of them had portal
      hypertension, with portal systemic collaterals. Liver biopsies showed liver
      sinusoids congestive dilatation, endothelization, and micronodularity fulfilling
      the criteria for noncirrhotic portal hypertension. Patients with portal vein
      enlargement had severe clinical and immunological phenotypes. CONCLUSIONS: In
      primary antibody deficient patients, infections, inflammations, splenomegaly,
      increased blood venous flow, and lymphocyte abnormalities contribute to
      establishment of liver damage possibly leading to noncirrhotic portal
      hypertension. Patients with primary antibody deficiency should be considered a
      good model to give insight into the pathological mechanisms underlying
      noncirrhotic portal hypertension.

PMID- 24741618
TI  - Isolated IgA anti- beta2 glycoprotein I antibodies in patients with clinical
      criteria for antiphospholipid syndrome.
AB  - Seronegative antiphospholipid syndrome (SNAPS) is an autoimmune disease present
      in patients with clinical manifestations highly suggestive of Antiphospholipid
      Syndrome (APS) but with persistently negative consensus antiphospholipid
      antibodies (a-PL). IgA anti-beta 2 Glycoprotein I (aB2-GPI) antibodies are
      associated with APS. However, they are not currently considered to be laboratory
      criteria due to the heterogeneity of published works and the use of poor
      standardized diagnostic systems. We have aimed to assess aPL antibodies in a
      group of patients with clinical manifestations of APS (C-APS) to evaluate the
      importance of the presence of IgA aB2GPI antibodies in APS and its relation with
      other aPL antibodies. Only 14% of patients with C-APS were positive for any
      consensus antibody, whereas the presence of isolated IgA aB2GPI antibodies was
      found in 22% of C-APS patients. In patients with arterial thrombosis IgA aB2GPI,
      antibodies were the only aPL antibodies present. Serologic profile in primary APS
      (PAPS) is different from systemic autoimmune disorders associated APS (SAD-APS).
      IgA aB2GPI antibodies are more prevalent in PAPS and IgG aB2GPI antibodies are
      predominant in SAD-APS. The analysis of IgA aB2GPI antibodies in patients with
      clinical manifestations of PAPS might avoid underdiagnosed patients and provide a
      better diagnosis in patients with SAD-APS. Laboratory consensus criteria might
      consider including analysis of IgA aB2GPI for APS diagnosis.

PMID- 24741617
TI  - Immune escape mechanisms in colorectal cancer pathogenesis and liver metastasis.
AB  - Over the past decade, growing evidence indicates that the tumor microenvironment
      (TME) contributes with genomic/epigenomic aberrations of malignant cells to
      enhance cancer cells survival, invasion, and dissemination. Many factors,
      produced or de novo synthesized by immune, stromal, or malignant cells, acting in
      a paracrine and autocrine fashion, remodel TME and the adaptive immune response
      culminating in metastasis. Taking into account the recent accomplishments in the
      field of immune oncology and using metastatic colorectal cancer (mCRC) as a
      model, we propose that the evasion of the immune surveillance and metastatic
      spread can be achieved through a number of mechanisms that include (a) intrinsic
      plasticity and adaptability of immune and malignant cells to paracrine and
      autocrine stimuli or genotoxic stresses; (b) alteration of positional schemes of
      myeloid-lineage cells, produced by factors controlling the balance between tumour
      suppressing and tumour-promoting activities; (c) acquisition by cancer cells of
      aberrant immune-phenotypic traits (NT5E/CD73, CD68, and CD163) that enhance the
      interactions among TME components through the production of immune-suppressive
      mediators. These properties may represent the driving force of metastatic
      progression and thus clinically exploitable for cancer prevention and therapy. In
      this review we summarize results and suggest new hypotheses that favour the
      growing impact of tumor-infiltrating immune cells on tumour progression,
      metastasis, and therapy resistance. 

PMID- 24741619
TI  - Immune response in the liver under conditions of infection, malignancy, and
      transplantation.

PMID- 24741621
TI  - Factors affecting health-related quality of life and physical activity after
      liver transplantation for autoimmune and nonautoimmune liver diseases: a
      prospective, single centre study.
AB  - BACKGROUND/AIM: With the improvement of the outcomes after liver transplantation
      (LTx), health-related quality of life (HRQoL) and physical activity are becoming
      significant outcome parameters. We prospectively assessed these parameters in
      patients with autoimmune and nonautoimmune liver disorders undergoing LTx.
      MATERIALS AND METHODS: Patients (n = 107) were subdivided into 3 groups depending
      on the time after LTx: group-A (n = 21): 6-12 months; group-B (n = 48): 13-36
      months; and group-C (n = 38): >37 months. SF-36 and IPAQ were applied in HRQoL
      and physical activity assessment. RESULTS: Females had impaired HRQoL in most SF
      36 domains. Younger patients showed higher scores at SF-36 physical functioning
      domain but IPAQ was not influenced by age. Group-B had higher general health and
      physical component summary than group-A (P = 0.037, P = 0.04, resp.) and total
      IPAQ than group-C (P = 0.047). The sitting time domain was longer in group-A than
      in group-B and group-C (P = 0.0157;  P = 0.042, resp.). Employed patients had
      better HRQoL and higher physical activity than those not working. SF-36 and IPAQ
      were unrelated to the autoimmune etiology of liver disease. CONCLUSIONS: These
      findings show that female and unemployed patients have worse HRQoL, while gender
      and age at LTx time do not affect IPAQ's physical activity. The autoimmune
      etiology of liver disease does not influence HRQoL and physical activity after
      LTx.

PMID- 24741620
TI  - Transcriptional and posttranscriptional regulations of the HLA-G gene.
AB  - HLA-G has a relevant role in immune response regulation. The overall structure of
      the HLA-G coding region has been maintained during the evolution process, in
      which most of its variable sites are synonymous mutations or coincide with
      introns, preserving major functional HLA-G properties. The HLA-G promoter region
      is different from the classical class I promoters, mainly because (i) it lacks
      regulatory responsive elements for IFN-gamma and NF-kappaB, (ii) the proximal
      promoter region (within 200 bases from the first translated ATG) does not mediate
      transactivation by the principal HLA class I transactivation mechanisms, and
      (iii) the presence of identified alternative regulatory elements (heat shock,
      progesterone and hypoxia-responsive elements) and unidentified responsive
      elements for IL-10, glucocorticoids, and other transcription factors is evident.
      At least three variable sites in the 3' untranslated region have been studied
      that may influence HLA-G expression by modifying mRNA stability or microRNA
      binding sites, including the 14-base pair insertion/deletion, +3142C/G and
      +3187A/G polymorphisms. Other polymorphic sites have been described, but there
      are no functional studies on them. The HLA-G coding region polymorphisms might
      influence isoform production and at least two null alleles with premature stop
      codons have been described. We reviewed the structure of the HLA-G promoter
      region and its implication in transcriptional gene control, the structure of the
      HLA-G 3'UTR and the major actors of the posttranscriptional gene control, and,
      finally, the presence of regulatory elements in the coding region.

PMID- 24741622
TI  - Atrioventricular conduction delay in the second trimester measured by fetal
      magnetocardiography.
AB  - INTRODUCTION: Fetal AV block in SSA/Ro pregnancies is generally not seen before
      18-week gestation and onset is rare after 28-week gestation. If complete AV block
      appears, it is believed to be irreversible. The purpose of the study was to
      evaluate precise electrophysiological AV conduction from 18-week gestation
      onwards. PATIENTS AND METHODS: 21 fetuses of pregnant women with collagen
      vascular diseases were included in the study group and 59 healthy fetuses served
      as controls. In addition to fetal echocardiography, fetal magnetocardiography
      (fMCG) was used to investigate precise electrophysiological fetal cardiac time
      intervals (fCTIs). RESULTS: The PR segment (isoelectric segment between the end
      of the P wave and the start of the QRS complex) was significantly prolonged (P <
      0.036 2nd trimester, P < 0.023 3rd trimester) in both trimesters within the study
      group. In fetuses less than 23-week gestational age, a nearly complete separation
      was found, where a PR segment of 60 ms or greater completely excluded control
      fetuses. All other fCTIs did not differ significantly. None of the fetuses
      progressed to a more advanced heart block. CONCLUSION: Slight antibody effects in
      pregnancy, leading to PR segment prolongation, can already be seen from 18-week
      gestation onwards by fMCG. Serial fetal Doppler echocardiography and additional
      fMCG can be useful methods to measure early and precise AV conduction time, to
      achieve best surveillance for these high-risk pregnancies.

PMID- 24741623
TI  - Immunological responses and epitope mapping by tuberculosis-associated antigens
      within the RD1 region in Japanese patients.
AB  - Tuberculosis remains a major global health problem worldwide, and hence there is
      a need for novel vaccines that better induce cellular-mediated immunity (CMI). In
      search of a better vaccine target, the QuantiFERON-TB Gold In-Tube Test (QFT-GIT)
      and the interferon-gamma ELISPOT assay (ELISPOT) were used to compare the
      magnitude of CMI in patients. Results of the ELISPOT assay led to the discovery
      of specific epitopes within the early secreted antigenic target 6 kDa (ESAT-6)
      and culture filtrate protein 10 kDa (CFP-10) proteins. Both peptides showed a
      strong association with several HLA class II DRB1 molecules in the Japanese
      population. Using ESAT-6-specific HLA class II tetramers, we determined that the
      expression of ESAT-6-specific CD4+ lymphocytes was significantly decreased in
      treated patients compared with active patients. In addition, programmed death-1
      (PD-1)/killer cell lectin-like receptor G1 (KLRG-1) double positive cells were
      found only in treated patients and not in those with active TB. These data could
      provide clues for the development of novel tuberculosis vaccines. 

PMID- 24741624
TI  - Model for vaccine design by prediction of B-epitopes of IEDB given perturbations
      in peptide sequence, in vivo process, experimental techniques, and source or host
      organisms.
AB  - Perturbation methods add variation terms to a known experimental solution of one
      problem to approach a solution for a related problem without known exact
      solution. One problem of this type in immunology is the prediction of the
      possible action of epitope of one peptide after a perturbation or variation in
      the structure of a known peptide and/or other boundary conditions (host organism,
      biological process, and experimental assay). However, to the best of our
      knowledge, there are no reports of general-purpose perturbation models to solve
      this problem. In a recent work, we introduced a new quantitative structure
      property relationship theory for the study of perturbations in complex
      biomolecular systems. In this work, we developed the first model able to classify
      more than 200,000 cases of perturbations with accuracy, sensitivity, and
      specificity >90% both in training and validation series. The perturbations
      include structural changes in >50000 peptides determined in experimental assays
      with boundary conditions involving >500 source organisms, >50 host organisms, >10
      biological process, and >30 experimental techniques. The model may be useful for
      the prediction of new epitopes or the optimization of known peptides towards
      computational vaccine design. 

PMID- 24741625
TI  - Gender differences of B cell signature in healthy subjects underlie disparities
      in incidence and course of SLE related to estrogen.
AB  - The aim of the present study was to investigate mechanism of the gender
      differences of B cells. The results showed that 358 differential gene expressions
      (DEGs) were displayed between healthy females and males. Compared with male, 226
      and 132 genes were found to be up- and downregulated in the female. 116 genes
      displayed possible correlation with estrogen. Moreover, the upregulated DEGs
      (Cav1, CD200R1, TNFRSF17, and CXCR3) and downregulated DEGs (EIF1AY and DDX3Y) in
      healthy female may be involved in gender predominance of some immune diseases.
      Furthermore, signaling pathway analysis for estrogen-relevant DEGs showed that
      only 26 genes were downregulated in SLE female versus SLE male, of which
      expressions of 8 genes had significant difference between SLE females and SLE
      males but are having nonsignificant difference between healthy females and
      healthy males. Except for the 5 Y-chromosome-related genes or varients, only 3
      DEGs (LTF, CAMP, and DEFA4) were selected and qRT-PCR confirmed that the
      expressions of LTF and CAMP decreased significantly in B cells from female SLE
      patients. These data indicated that the gender differences were existent in
      global gene expression of B cells and the difference may be related to estrogen. 

PMID- 24741626
TI  - The effect of combination therapy with rituximab and intravenous immunoglobulin
      on the progression of chronic antibody mediated rejection in renal transplant
      recipients.
AB  - The treatment for chronic active antibody-mediated rejection (CAMR) remains
      controversial. We investigated the efficacy of rituximab (RTX) and intravenous
      immunoglobulin (IVIg) for CAMR. Eighteen patients with CAMR were treated with RTX
      (375 mg/m(2)) and IVIg (0.4 g/kg) for 4 days. The efficacy of RTX/IVIg
      combination therapy (RIT) was assessed by decline in estimated glomerular
      filtration rate per month (DeltaeGFR) before and after RIT. Patients were divided
      into responder and nonresponder groups based on decrease and no decrease in
      DeltaeGFR, respectively, and their clinical and histological characteristics were
      compared. Response rate to RIT was 66.7% (12/18), and overall DeltaeGFR decreased
      significantly to 0.4 +/- 1.7 mL.min(-1) .1.73 m(-2) per month 6 months after RIT
      compared to that observed 6 months before RIT (1.8 +/- 1.0, P < 0.05). Clinical
      and histological features between the 12 responders and the 6 nonresponders were
      not significantly different, but nonresponders had a significantly higher
      proteinuria levels at the time of RIT (2.5 +/- 2.5 versus 7.0 +/- 3.5
      protein/creatinine (g/g), P < 0.001). The effect of the RIT on DeltaeGFR had
      dissipated in all patients by 1 year post-RIT. Thus, RIT delayed CAMR
      progression, and baseline proteinuria level was a prognostic factor for response
      to RIT.

PMID- 24741628
TI  - Increased levels of granulocytic myeloid-derived suppressor cells in peripheral
      blood and tumour tissue of pancreatic cancer patients.
AB  - Pancreatic cancer (PC) often presents late with poor survival. While role of
      immunosuppressive cells in preclinical studies provided help to develop
      immunotherapeutic agents, these cells remain under investigation in PC. The aim
      of this study was to characterise the different subsets of myeloid-derived
      suppressor cells (MDSCs) and evaluate their level and function in the circulation
      and tissue of PC patients. Significant increases in circulating and tumour
      infiltrating granulocytic (Lin-HLA-DR-CD33+CD11b+CD15+), but not monocytic (Lin
      HLA-DR-CD14+), MDSCs were detected in PC patients when compared with healthy
      donors and patients with chronic pancreatitis. The circulating MDSCs from PC
      patients expressed arginase 1, which represents their functional state. Blood
      levels of MDSCs showed no association with PC stage or preoperative levels of
      tumour markers. These findings provide a first characterisation of the phenotype
      of different subsets of peripheral and local MDSCs in PC patients and suggest
      that the frequency and contribution of these cells are predominantly
      granulocytic. This information demonstrates that MDSCs play a role in pancreatic
      cancer and future large validation studies may help in the development of new
      immunotherapeutic strategies to inhibit or eliminate MDSC function. 

PMID- 24741627
TI  - Type 2 diabetes, PUFAs, and vitamin D: their relation to inflammation.
AB  - Chronic diseases have become one of the most important public health problems,
      due to their high costs for treatment and prevention. Until now, researchers have
      considered that the etiology of Type 2 diabetes mellitus (T2DM) is
      multifactorial. Recently, the study of the innate immune system has offered an
      explanation model of the pathogenesis of T2DM. On the other hand, there is
      evidence about the beneficial effect of polyunsaturated fatty acids (PUFA) n-3
      and n-6 in patients with chronic inflammatory diseases including diabetes.
      Furthermore, high vitamin D plasmatic concentrations have been associated with
      the best performance of pancreatic beta cells and the improving of this disease.
      In conclusion, certain fatty acids in the adequate proportion as well as 25
      hydroxivitamin D can modulate the inflammatory response in diabetic people,
      modifying the evolution of this disease. 

PMID- 24741630
TI  - Immunoregulation of inflammation in chronic kidney disease.

PMID- 24741629
TI  - Clinical studies applying cytokine-induced killer cells for the treatment of
      gastrointestinal tumors.
AB  - Tumors of the gastrointestinal system represent a significant share of solid
      tumors worldwide. Despite the advances in diagnosis and treatment, the prognosis
      of gastrointestinal tumors is still very poor and improved therapies are
      indispensable. Cytokine-induced killer (CIK) cells are feasible for an
      immunotherapeutic approach as they are easily available and have an advantageous
      biologic profile; they are rapidly proliferating and their high cytotoxicity is
      non-MHC-restricted. We summarize and discuss twenty recent clinical studies
      applying CIK cells for the treatment of gastric, pancreatic, hepatocellular, and
      colorectal cancer. Autologous CIK cells were transfused intravenously,
      intraperitoneally, or via the common hepatic artery. In all studies side effects
      and toxicity of CIK cell therapy were mild and easily controllable. The
      combination of CIK cell therapy with conventional adjuvant or palliative
      therapies was superior to the standard therapy alone, indicating the benefit of
      CIK cell therapy for cancer patients. Thus, CIK cells represent a promising
      immunotherapy for the treatment of gastrointestinal tumors. The optimal treatment
      schedule and ideal combination with conventional therapies should be evaluated in
      further clinical studies. 

PMID- 24741631
TI  - Ursodeoxycholic acid influences the expression of p27kip1 but not FoxO1 in
      patients with non-cirrhotic primary biliary cirrhosis.
AB  - BACKGROUND: Enhanced expression of cell cycle inhibitor p27(kip1) suppresses cell
      proliferation. Ursodeoxycholic acid (UDCA) delays progression of primary biliary
      cirrhosis (PBC) but its effect on p27(kip1) expression is uncertain. AIMS: To
      analyze the expression of p27(kip1) and its transcription modulator FoxO1 in
      patients with PBC, and to assess the impact of UDCA on this pathway. MATERIALS
      AND METHODS: The examined human tissue included explanted livers from patients
      with cirrhotic PBC (n = 23), primary sclerosing cholangitis (PSC; n = 9),
      alcoholic liver disease (ALD; n = 9), and routine liver biopsies from patients
      with non-cirrhotic PBC (n = 26). Healthy liver samples served as controls (n =
      19). Livers of FoxO-deficient mice were also studied. mRNA and protein
      expressions were analyzed by real-time PCR and Western blot. RESULTS: p27(kip1)
      expression was increased in cirrhotic and non-cirrhotic PBC. FoxO1 mRNA levels
      were increased in PBC (8.5-fold increase versus controls). FoxO1 protein
      expression in PBC was comparable to controls, but it was decreased in patients
      with PSC and ALD (63% and 70% reduction, respectively; both P < 0.05 versus
      control). UDCA-treated non-cirrhotic patients with PBC showed decreased
      expression of p27(kip1) mRNA. CONCLUSION: PBC progression is characterized by a
      FoxO1-independent increase of p27(kip1) expression. In early PBC, UDCA may
      enhance liver regeneration via p27(kip1)-dependent mechanism.

PMID- 24741632
TI  - Polarization of ILC2s in peripheral blood might contribute to immunosuppressive
      microenvironment in patients with gastric cancer.
AB  - Newly identified nuocytes or group 2 innate lymphoid cells (ILC2s) play an
      important role in Th2 cell mediated immunity such as protective immune responses
      to helminth parasites, allergic asthma, and chronic rhinosinusitis. However, the
      contributions of ILC2s in the occurrence and development of cancer remain
      unknown. Our previous study found that there was a predominant Th2 phenotype in
      patients with gastric cancer. In this study, the ILC2s related genes or molecules
      in PBMC from patients with gastric cancer were measured, and the potential
      correlation between them was analyzed. The expression levels of RORalpha, GATA3,
      T1/ST2, IL-17RB, CRTH2, IL-33, IL-5, and IL-4 mRNA were significantly increased
      in patients, but no significant changes were found in ICOS, CD45, and IL-13
      expression, and there was a positive correlation between RORalpha or IL-13 and
      other related factors, such as ICOS and CD45. The increased frequency of ILC2s
      was also found in PBMC of patients by flow cytometry. In addition, the mRNA of
      Arg1 and iNOS were also significantly increased in patients. These results
      suggested that there are polarized ILC2s in gastric cancer patients which might
      contribute to immunosuppressive microenvironment and closely related to the
      upregulation of MDSCs and M2 macrophages.

PMID- 24741633
TI  - IL-27 driven upregulation of surface HLA-E expression on monocytes inhibits IFN
      gamma release by autologous NK cells.
AB  - HLA-G and HLA-E are HLA-Ib molecules with several immunoregulatory properties.
      Their cell surface expression can be modulated by different cytokines. Since IL
      27 and IL-30 may either stimulate or regulate immune responses, we have here
      tested whether these cytokines may modulate HLA-G and -E expression and function
      on human monocytes. Monocytes expressed gp130 and WSX-1, the two chains of IL27
      receptor (R), and IL6Ralpha (that serves as IL-30R, in combination with gp130).
      However, only IL27R appeared to be functional, as witnessed by IL-27 driven
      STAT1/ STAT3 phosphorylation. IL-27, but not IL-30, significantly upregulated HLA
      E (but not HLA-G) expression on monocytes. IFN-gamma; secretion by activated NK
      cells was dampened when the latter cells were cocultured with IL-27 pretreated
      autologous monocytes. Such effect was not achieved using untreated or IL-30
      pretreated monocytes, thus indicating that IL-27 driven HLA-E upregulation might
      be involved, possibly through the interaction of this molecule with CD94/NKG2A
      inhibitory receptor on NK cells. In contrast, cytotoxic granules release by NK
      cell in response to K562 cells was unaffected in the presence of IL-27 pretreated
      monocytes. In conclusion, we delineated a novel immunoregulatory function of IL
      27 involving HLA-E upregulation on monocytes that might in turn indirectly impair
      some NK cell functions.

PMID- 24741634
TI  - Unique cytokine signature in the plasma of patients with fibromyalgia.
AB  - Fibromyalgia (FMS) is a chronic pain syndrome with a complex but poorly
      understood pathogenesis affecting approximately 10 million adults in the United
      States. The lack of a clear etiology of FMS has limited the effective diagnosis
      and treatment of this debilitating condition. The objective of this secondary
      data analysis was to examine plasma cytokine levels in women with FMS using the
      Bio-Plex Human Cytokine 17-plex Assay. Post hoc analysis of plasma cytokine
      levels was performed to evaluate patterns that were not specified a priori. Upon
      examination, patients with FMS exhibited a marked reduction in T(H)2 cytokines
      such as IL-4, IL-5, and IL-13. The finding of this pattern of altered cytokine
      milieu not only supports the role of inflammation in FMS but also may lead to
      more definitive diagnostic tools for clinicians treating FMS. The TH2 suppression
      provides strong evidence of immune dysregulation in patients with FMS.

PMID- 24741635
TI  - The expression of Bcl-2 and BID in gastric cancer cells.
AB  - BACKGROUND: Bcl-2 and BID play a major role in the process of apoptosis and their
      dysfunction underlies carcinogenesis. The study objective was to assess the
      expression of Bcl-2 and BID in gastric cancer cells in correlation with chosen
      clinicopathological parameters, presence of Helicobacter pylori infection, and
      patients' survival. MATERIALS AND METHODS: The study involved 88 patients
      operated on for gastric cancer. The expressions of Bcl-2 and BID were determined
      immunohistochemically. RESULTS: Positive Bcl-2 expression was found in 55.7% and,
      BID in 53.6% of patients. The Bcl-2 expression correlated with stage pT3 and T4
      gastric cancer (P < 0.05), with the intestinal type according to Lauren (P <
      0.001), ulcerated type according to Bormann's classification (P < 0.01), and with
      local lymph node metastases (P < 0.05). CONCLUSION: The Bcl-2 protein plays a key
      role in the process of gastric cancer formation and is associated with the growth
      of definite types of gastric cancer.

PMID- 24741636
TI  - gammadelta T cell and other immune cells crosstalk in cellular immunity.
AB  - gammadelta T cells have been recognized as effectors with immunomodulatory
      functions in cellular immunity. These abilities enable them to interact with
      other immune cells, thus having the potential for treatment of various immune
      mediated diseases with adoptive cell therapy. So far, the interactions between
      gammadelta T cell and other immune cells have not been well defined. Here we will
      discuss the interactivities among them and the perspective on gammadelta T cells
      for their use in immunotherapy could be imagined. The understanding of the
      crosstalk among the immune cells in immunopathology might be beneficial for the
      clinical application of gammadelta T cell. 

PMID- 24741637
TI  - Oxidative stress is differentially present in multiple sclerosis courses, early
      evident, and unrelated to treatment.
AB  - BACKGROUND: Oxidative stress is well documented in multiple sclerosis (MS)
      lesions, but its correspondence at peripheral level is still controversial.
      Objective. To evaluate peripheral oxidative stress markers in MS patients.
      METHODS: We studied total blood levels of Coenzyme Q10 (CoQ10), oxidized and
      reduced forms of glutathione, malondialdehyde, reactive oxygen species (ROS),
      anti-oxidized-low-density lipoproteins (anti-oxLDL) antibodies, and antioxidant
      power (PAO) in 87 patients with different MS clinical phenotypes and in 77
      controls. RESULTS: CoQ10 was lower whereas anti-oxLDL antibodies titer was higher
      in MS patients than in controls. The benign variant of MS displayed both higher
      CoQ10 and higher anti-oxLDL than other MS clinical variants. Female patients had
      lower CoQ10 and PAO and higher ROS than male patients. Differences were greater
      in younger patients with shorter disease duration. Surprisingly, there was no
      difference for these markers between treated and untreated patients. CONCLUSION:
      We found lower antioxidant agents and higher anti-oxLDL antibodies in MS, and the
      highest antibody titers occurred in the benign form. We suggest that natural anti
      oxLDL antibodies can be protective against MS, saving blood brain barrier
      integrity. Our findings also suggest that milder MS is associated with a distinct
      oxidative stress pattern, which may provide a useful biomarker of disease
      prognosis.

PMID- 24741638
TI  - microRNAs as a new mechanism regulating adipose tissue inflammation in obesity
      and as a novel therapeutic strategy in the metabolic syndrome.
AB  - Obesity is associated closely with the metabolic syndrome (MS). It is well known
      that obesity-induced chronic inflammation plays a fundamental role in the
      pathogenesis of MS. White adipose tissue (AT) is the primary site for the
      initiation and exacerbation of obesity-associated inflammation. Exploring the
      mechanisms of white AT inflammation and resetting the immunological balance in
      white AT could be crucial for the management of MS. Several prominent molecular
      mechanisms have been proposed to mediate inflammation in white AT, including
      hypoxia, endoplasmic reticulum stress, lipotoxicity, and metabolic endotoxemia.
      Recently, a growing body of evidence supports the role of miRNAs as a new
      important inflammatory mediator by regulating both the adaptive and innate
      immunity. This review will focus on the implication of miRNAs in white AT
      inflammation in obesity, and will also highlight the potential of miRNAs as
      targets for therapeutic intervention in MS as well as the challenges lying in
      miRNA-targeting therapeutics. 

PMID- 24741639
TI  - Expression of neural markers by undifferentiated mesenchymal-like stem cells from
      different sources.
AB  - The spontaneous expression of neural markers, already demonstrated in bone marrow
      (BM) mesenchymal stem cells (MSCs), has been considered as evidence of the MSCs'
      predisposition to differentiate toward neural lineages, supporting their use in
      stem cell-based therapy for neural repair. In this study we have evaluated, by
      immunocytochemistry, immunoblotting, and flow cytometry experiments, the
      expression of neural markers in undifferentiated MSCs from different sources:
      human adipose stem cells (hASCs), human skin-derived mesenchymal stem cells (hS
      MSCs), human periodontal ligament stem cells (hPDLSCs,) and human dental pulp
      stem cells (hDPSCs). Our results demonstrate that the neuronal markers beta III
      tubulin and NeuN, unlike other evaluated markers, are spontaneously expressed by
      a very high percentage of undifferentiated hASCs, hS-MSCs, hPDLSCs, and hDPSCs.
      Conversely, the neural progenitor marker nestin is expressed only by a high
      percentage of undifferentiated hPDLSCs and hDPSCs. Our results suggest that the
      expression of beta III-tubulin and NeuN could be a common feature of stem cells
      and not exclusive to neuronal cells. This could result in a reassessment of the
      use of beta III-tubulin and NeuN as the only evidence proving neuronal
      differentiation. Further studies will be necessary to elucidate the relevance of
      the spontaneous expression of these markers in stem cells. 

PMID- 24741640
TI  - Rapamycin regulates iTreg function through CD39 and Runx1 pathways.
AB  - It has been shown that rapamycin is able to significantly increase the expression
      of FoxP3 and suppress activity in induced Treg (iTreg) cells in vivo and in
      vitro. CD39 is a newly determined Treg marker that relates to cell suppression.
      Runx1, a regulator of FoxP3, controls the expression of adenosine deaminase (ADA)
      gene, which is found recently in the downstream of CD39 pathway in trophoblast
      cells. Whether rapamycin would influence CD39 pathway and regulate the expression
      of Runx1 remains to be determined. The addition of rapamycin to human CD4(+)
      naive cells in the presence of IL-2, TGF-beta promotes the expression of FoxP3.
      In this paper, we found that CD39 positively correlated with the FoxP3 expression
      in iTreg cells. Rapamycin induced iTreg cells showed a stronger CD39/Runx1
      expression with the enhanced suppressive function. These data suggested that CD39
      expression was involved in iTreg generation and the enhanced suppressive ability
      of rapamycin induced Treg was partly due to Runx1 pathway. We conclude that
      rapamycin favors CD39/Runx1 expression in human iTreg and provides a novel
      insight into the mechanisms of iTreg generation enhanced by rapamycin.

PMID- 24741642
TI  - Pharmacists' opinions and self-reporting performance regarding the professional
      tasks and responsibilities in Isfahan, Iran.
AB  - BACKGROUND: The pharmacists' roles and responsibilities toward the pharmaceutical
      care practice have developed considerably during the recent years. OBJECTIVES:
      The aim of this program is to explore the opinions and performances of community
      pharmacists with regard to their professional tasks and responsibilities in
      Isfahan city. MATERIALS AND METHODS: A descriptive cross-sectional questionnaire
      survey of community pharmacists was conducted on a sample of 150 pharmacists
      using the Delphi process. Data were collected on the opinions and performances of
      the pharmacists' task, professional responsibility and expertise, organizational
      and managing skills, and sociodemographic information. RESULTS: The response rate
      was 93.3%. High expressions of agreement were found with most of the task and
      professional responsibilities and managerial skills and the mean rates of the
      self-reporting performance of most key tasks were 'always'. The important
      differences were found in two opinions about the pharmacists' responsibilities,
      (a) declining to dispense the prescribed drug that was not appropriate for the
      patient's illness and (b) keeping the patient's medical records for future needs.
      The pharmacists' opinions on various forms of professional expertise were
      diverse, especially on recognizing that the required medications were not
      prescribed for the patient, being informed on the pharmacotherapy subsequence and
      predicting the therapeutic outcomes, interpreting the laboratory tests results,
      and assisting persons in need of emergency first aid. CONCLUSION: Pharmacists
      largely agreed with most of the professional tasks and responsibilities, however,
      new educational programs should be developed to promote the pharmacists'
      knowledge and skills concerning pharmacotherapy. Also an extended role for
      pharmacists needs to be addressed in the pharmacy regulations and laws.

PMID- 24741641
TI  - The prevention and control the type-2 diabetes by changing lifestyle and dietary
      pattern.
AB  - Type-2 diabetes is a major, non-communicable disease with increasing prevalence
      at a global level. Type-2 diabetes results when the body does not make enough
      insulin or the body cannot use the insulin it produces. Type-2 diabetes is the
      leading cause of premature deaths. Improperly managed, it can lead to a number of
      health issues, including heart diseases, stroke, kidney disease, blindness, nerve
      damage, leg and foot amputations, and death. Type-2 diabetes or adult-onset
      diabetes is most common type of diabetes, usually begins when a person is in his
      or her mid-50s, but diabetes is not inevitable. Minor changes in your lifestyle
      can greatly reduce your chances of getting this disease. Therefore, in order to
      prevent this condition, action should be taken regarding the modifiable factors
      that influence its development-lifestyle and dietary habits. However, with proper
      testing, treatment and lifestyle changes, healthy eating as a strategy, promote
      walking, exercise, and other physical activities have beneficial effects on human
      health and prevention or treatment of diabetes, promoting adherence to this
      pattern is of considerable public health importance. 

PMID- 24741643
TI  - Compiling of curriculum for the Master of Science in genetic counseling.
AB  - INTRODUCTION: The demand for genetic counseling has been greatly increased in the
      recent years in Iran and the entire world. However, there are no systematic
      training courses for genetic counseling in the country. The purpose of this
      research was compiling the curriculum for the Master of Science (MSc) in genetic
      counseling. MATERIALS AND METHODS: This descriptive study was conducted in 2010
      and 2011 in Isfahan University of Medical Sciences. A questionnaire with 25
      questions was prepared based on the literature review. The assessment was
      conducted by using the questionnaire as well as outcome of group discussions with
      three geneticist groups including, members of the board of medical genetics,
      genetics graduate students, and practitioners in genetic counseling. The
      curriculum was designed after determining the educational needs and priorities by
      the genetic board. RESULTS: The results of this research led to set the
      educational goals for the MSc in genetic counseling. Finally, the course
      curriculum was compiled. DISCUSSION: The designed MSc in genetic counseling in
      this study was generally similar with the courses in other universities.
      Although, the assessment results were different in some cases with the same
      academic courses such as to give more importance to basic medical needs in
      comparison with the needs of clinical sciences. Therefore, more attention should
      be paid on prerequisite courses rather than the rotational periods in the
      hospital. Among the reasons for this difference, it could be noted to the
      differences in undergraduate educations and differences in the status of provided
      genetics services in Iran. The final conclusion of this research was to design a
      fundamental course to overcome one of the severely tangible requirements in the
      country field of health, namely genetic counseling.

PMID- 24741644
TI  - Evaluation of dietary habits and related factors among type 2 diabetic patients:
      An innovative study in Iran.
AB  - INTRODUCTION: The aim of this study was to assess dietary habits and related
      factors among type 2 diabetic mellitus patients for designing an effective
      nutrition intervention. MATERIALS AND METHODS: A descriptive-analytical study was
      performed on 480 diabetic patients referred to four selected teaching hospitals
      affiliated to the Tehran University of Medical Sciences (TUMS) in Tehran for a
      period of nine months in 2012. Patients' dietary habits were measured by a 51
      item self-report instrument with four general questions about dietary habits and
      four subscales reflecting domains including general diabetes information (12
      items), planning, shopping for, and preparing meals (6 items), eating meals (17
      items), and family influence on dietary habits (12 items). The collected data was
      analyzed by using SPSS software version 11.5. Results were considered significant
      at a conventional P < 0.05 level. RESULTS: Mean age of the participants was 59.96
      +/- 11.53 years. Mean scores in the domains were (53.72 +/- 19.83), (57.31 +/-
      23.82), (52.27 +/- 12.13), and (64.72 +/- 14.3), respectively. Family influence
      on dietary habits was highlighted as the most important domain in the dietary
      habits instrument. Study results revealed that there was a significant
      association between the four domains and socioeconomic and some variables related
      to dietary habits such as dietary self-management, planned healthy lifestyle and
      attending diabetes educational programs. DISCUSSION: The important role of family
      on dietary habits among type 2 diabetic patients highlighted the role of
      perceived social support from the family. The results of the sociodemographic
      variables stressed the necessity of tailoring specific intervention programs
      accordingly.

PMID- 24741645
TI  - A school-based education concerning poisoning prevention in Isfahan, Iran.
AB  - BACKGROUND: A school-based poisoning prevention program for young school children
      was implemented and evaluated in Isfahan city by Poison Control Center (PCC) of
      Food and Drug Deputy in 2010. OBJECTIVES: The aim of the program was to evaluate
      the effectiveness of education on children's knowledge on poisoning and its
      consequence and also on their attitude in case of exposure to poisonous or
      hazardous substances and poisoned patient. MATERIALS AND METHODS: In a pretest
      posttest design, samples of 520 students from the fifth grade (10-11 years old),
      from twenty randomly selected girls' and boys' primary schools were involved in
      the study. These children were from two different geographical locations with
      different socio-economical levels (high-income and middle-income). After
      collection of pretest questionnaires, 6 poisoning education sessions were
      implemented in selected schools by trained teachers in a week. RESULTS: Following
      the education program, knowledge on various issues of poisoning significantly
      improved as did attitude to the poisonous agents and poisoned patients. In girl
      students, strong increase was found in knowledge on poisoning with carbon
      monoxide and heating devices from pretest to posttest. While in boy students, the
      strongest increase was in item of knowledge on poisoning prevention. Children
      living in the regions with middle-income conditions had more base-line knowledge
      and attitudinal aspect when compared with children with high-income condition.
      Comparison of all students showed significant differences (P < 0.001) on
      knowledge scores on various issues of poisoning before and after education.
      CONCLUSION: The school-based educational programs provide a good opportunity to
      poison information centers in preventing poisoning.

PMID- 24741646
TI  - Hyper Text Mark-up Language and Dublin Core metadata element set usage in
      websites of Iranian State Universities' libraries.
AB  - INTRODUCTION: Recent progress in providing innovative solutions in the
      organization of electronic resources and research in this area shows a global
      trend in the use of new strategies such as metadata to facilitate description,
      place for, organization and retrieval of resources in the web environment. In
      this context, library metadata standards have a special place; therefore, the
      purpose of the present study has been a comparative study on the Central
      Libraries' Websites of Iran State Universities for Hyper Text Mark-up Language
      (HTML) and Dublin Core metadata elements usage in 2011. MATERIALS AND METHODS:
      The method of this study is applied-descriptive and data collection tool is the
      check lists created by the researchers. Statistical community includes 98
      websites of the Iranian State Universities of the Ministry of Health and Medical
      Education and Ministry of Science, Research and Technology and method of sampling
      is the census. Information was collected through observation and direct visits to
      websites and data analysis was prepared by Microsoft Excel software, 2011.
      RESULTS: The results of this study indicate that none of the websites use Dublin
      Core (DC) metadata and that only a few of them have used overlaps elements
      between HTML meta tags and Dublin Core (DC) elements. The percentage of overlaps
      of DC elements centralization in the Ministry of Health were 56% for both
      description and keywords and, in the Ministry of Science, were 45% for the
      keywords and 39% for the description. But, HTML meta tags have moderate presence
      in both Ministries, as the most-used elements were keywords and description (56%)
      and the least-used elements were date and formatter (0%). CONCLUSION: It was
      observed that the Ministry of Health and Ministry of Science follows the same
      path for using Dublin Core standard on their websites in the future. Because
      Central Library Websites are an example of scientific web pages, special
      attention in designing them can help the researchers to achieve faster and more
      accurate information resources. Therefore, the influence of librarians' ideas on
      the awareness of web designers and developers will be important for using
      metadata elements as general, and specifically for applying such standards.

PMID- 24741647
TI  - Determination of preventive behaviors for pandemic influenza A/H1N1 based on
      protection motivation theory among female high school students in Isfahan, Iran.
AB  - INTRODUCTION: Influenza A/H1N1 pandemic has recently threatened the health of
      world's population more than ever. Non-pharmaceutical measures are important to
      prevent the spread of influenza A/H1N1 and to prevent a pandemic. Effective
      influenza pandemic management requires understanding of the factors influencing
      preventive behavioral. This study reports on predictors of students' preventive
      behaviors for pandemic influenza A/H1N1 using variables based on the protection
      motivation theory (PMT). MATERIALS AND METHODS: In a cross-sectional study,
      multiple-stage randomized sampling was used to select 300 female students in
      Isfahan who completed a questionnaire in December 2009. Data were collected using
      a self-report questionnaire based on PMT. The statistical analysis of the data
      included bivariate correlations, Mann-Whitney, Kruskal-Wallis, and linear
      regression. RESULTS: The mean age of participants was 15.62 (SE = 1.1) years old.
      Majority of participants were aware regarding pandemic influenza A/H1N1 (87.3%,
      262 out of 300). Results showed that, protection motivation was highly
      significant relationship with preventive behavior and predicted 34% of its
      variance. We found all of the variables with the exception of perceived
      susceptibility, perceived severity, and response cost were related with
      protection motivation and explained 22% of its variance. CONCLUSION: Promotion of
      students' self-efficacy, and intention to protect themselves from a health threat
      should be priorities of any programs aimed at promoting preventive behaviors
      among students. It is also concluded that the protection motivation theory may be
      used in developing countries, like Iran, as a framework for prevention
      interventions in an attempt to improve the preventive behaviors of students.

PMID- 24741648
TI  - An assessment of the role of perceived benefits, barriers and self-efficacy in
      predicting dietary behavior in male and female high school students in the city
      of Izeh, Iran.
AB  - INTRODUCTION: Paying attention to improving the nutritional status of adolescents
      can be one of the most effective fundamental measures for preventing chronic
      diseases, particularly cardiovascular diseases in later life. Identifying the
      predicting elements in different behaviors is one of the most effective ways that
      can be considered in prevention programs in different communities, particularly
      in developing countries. The purpose of was to determine the perceived efficacy,
      benefits and barriers related to a healthy nutrition pattern and the relation of
      these variables with a healthy diet in male and female high school students in
      Izeh city. MATERIALS AND METHODS: In this cross-sectional descriptive and
      analytic study conducted throughout high schools in Izeh City, the subjects were
      500 students (300 girls and 200 boys) from the 1390-91 school years who were
      selected through the multistage random sampling method; the acquired data was
      then studied and analyzed. The data for this study was gathered through a multi
      sectional questionnaire (that included demographic characteristics, self
      efficacy, perceived benefits and barriers). The Independent t-test, Spearman's
      Correlation, Pearson's Correlation Coefficient and Linear Regression were used to
      interpret and analyze the data. RESULTS: Data analysis showed that the mean age
      of male participants was 15.67 +/- 0.95 years and females 15.86 +/- 1.16 years.
      The mean score for healthy eating patterns in male students was 46.83 +/- 14.86
      and in female students 44.20 +/- 14.16 respectively. The mean score for perceived
      benefits of healthy eating in girls was significantly higher than that in boys.
      There was a direct meaningful relationship between the mean score of benefits and
      perceived self-efficacy with the healthy eating behaviors in the two sexes, (P <
      0.001). The results of the multiple linear regression analysis revealed that the
      most important predictive factors in the students' healthy eating behavior are
      self-efficacy and perceived benefits respectively and that perceived barriers is
      not an influencing predictor in healthy eating patterns. CONCLUSION: The results
      of this study showed that many factors influence students' diet pattern and
      undeniably the role of these factors are not alike in the two sexes. The results
      also showed that perceived self-efficacy and benefits of healthy nutrition
      strengthens healthy eating behavior in students and thus these factors should be
      considered by health authorities in the country in any future programming.

PMID- 24741649
TI  - Exercise and academic performance among nursing and kinesiology students at US
      colleges.
AB  - CONTEXT: Lack of physical activity is a contributor to the obesity epidemic and
      is speculated to relate to reduced academic performance; however, this link has
      yet to be examined within the college population. AIMS: The purpose of this study
      in a group of undergraduate students, was to determine if aerobic exercise
      activity was related to academic performance. MATERIALS AND METHODS: The
      participants for this study included 740 students at multiple universities
      enrolled in nursing and kinesiology studies. The participants completed the
      Leisure and Physical Activity Questionnaire. RESULTS: Pearson's chi(2) analysis
      revealed differences in grade point average with aerobic activity (chi(2) =
      44.29, P <= 0.001) as well as a trend toward differences in grade point average
      with weightlifting activity (chi(2) = 22.69, P = 0.61). CONCLUSIONS: Based on
      these findings it can be suggested that college students engage in greater
      aerobic exercise.

PMID- 24741650
TI  - Sexual behavioral abstine HIV/AIDS questionnaire: Validation study of an Iranian
      questionnaire.
AB  - BACKGROUND: This study was designed to assess the validity and reliability of the
      designed sexual, behavioral abstinence, and avoidance of high-risk situation
      questionnaire (SBAHAQ), with an aim to construct an appropriate development tool
      in the Iranian population. MATERIALS AND METHODS: A descriptive-analytic study
      was conducted among female undergraduate students of Tehran University, who were
      selected through cluster random sampling. After reviewing the questionnaires and
      investigating face and content validity, internal consistency of the
      questionnaire was assessed by Cronbach's alpha. Explanatory and confirmatory
      factor analysis was conducted using SPSS and AMOS 16 Software, respectively.
      RESULTS: The sample consisted of 348 female university students with a mean age
      of 20.69 +/- 1.63 years. The content validity ratio (CVR) coefficient was 0.85
      and the reliability of each section of the questionnaire was as follows:
      Perceived benefit (PB; 0.87), behavioral intention (BI; 0.77), and self-efficacy
      (SE; 0.85) (Cronbach's alpha totally was 0.83). Explanatory factor analysis
      showed three factors, including SE, PB, and BI, with the total variance of 61%
      and Kaiser-Meyer-Olkin (KMO) index of 88%. These factors were also confirmed by
      confirmatory factor analysis [adjusted goodness of fitness index (AGFI) = 0.939,
      root mean square error of approximation (RMSEA) = 0.039]. CONCLUSION: This study
      showed the designed questionnaire provided adequate construct validity and
      reliability, and could be adequately used to measure sexual abstinence and
      avoidance of high-risk situations among female students.

PMID- 24741651
TI  - An audit of blood bank services.
AB  - BACKGROUND: An audit is a written series of simple, direct questions, which when
      answered and reviewed, tell whether the laboratory is performing its procedures,
      activities, and policies correctly and on time. AIM: The aim of this study is to
      briefly highlight the importance of audit in blood bank services. MATERIALS AND
      METHODS: An Audit of Blood Bank Services was carried out in a Blood bank of the
      tertiary care hospital, Central India by using the tool kit, (comprised of
      checklists) developed by Directorate General of Health Services, Dhaka WHO, July
      2008. RESULTS: After going through these checklists, we observed that there is no
      system for assessing the training needs of staff in the blood bank. There was no
      provision for duty doctor's room, expert room, medical technologist room and duty
      care service. There was no checklist for routine check for observation of
      hemolysis and deterioration of blood and plasma. There was no facility for
      separate private interview to exclude sexual disease in the donor. Requisition
      forms were not properly filled for blood transfusion indications. There was no
      facility for notification of donors who are permanently deferred. There were no
      records documented for donors who are either temporarily or permanently deferred
      on the basis of either clinical examination, history, or serological examination.
      It was found that wearing of apron, cap, and mask was not done properly except in
      serology laboratory. When the requisition forms for blood transfusions were
      audited, it was found that many requisition forms were without indications.
      CONCLUSION: Regular audit of blood bank services needs to be initiated in all
      blood banks and the results needs to be discussed among the managements,
      colleagues, and staffs of blood bank. These results will provide a good
      opportunity for finding strategies in improving the blood bank services with
      appropriate and safe use of blood.

PMID- 24741652
TI  - Investigating the faculty evaluation system in Iranian Medical Universities.
AB  - INTRODUCTION: To achieve a valid evaluation of faculty members, it is necessary
      to develop an inclusive and dynamic system of evaluation addressing all the
      activities and responsibilities of faculty members. Among these responsibilities,
      educational activities comprise an important part which needs to be investigated.
      This study aimed to investigate the current system of evaluating the faculty
      members' educational duties. METHODS: In this descriptive cross-sectional study,
      a checklist for investigating the current evaluation system and was developed
      confirmed by a focus group. The data for checklist were collected through a
      researcher-made questionnaire and interview with eight experts of faculty
      evaluation that worked in different Iranian Medical Universities. For completion
      of information, the available documents and records were studied. Finally, the
      current evaluation system of different universities was depicted. RESULTS: The
      developed checklist had six themes and 123 subthemes. The extracted themes
      included: Tools, evaluators, processes, appropriateness of faculty field of work
      with evaluation, feedback status, and university status regarding decisions made
      based on faculty evaluation results. As for comprehensiveness, all evaluation
      items except for evaluation and assessment skills and religiosity from
      personality traits subtheme were fully investigated. The evaluation tools were
      not enough for different types of education such as clinical education. In six
      universities, the feedbacks provided were only for making inter/intra department
      comparison, and no scientific suggestions were included. The results of
      evaluations were used only for the faculties' promotions. DISCUSSION: Suitability
      between evaluation and performance components is a necessity in every evaluation
      system. The study showed this does not exist in Iranian Universities. For
      instance, there was no appropriate tool for the evaluation of clinical education.
      Also, the results of the faculty evaluation were not used for the improvement of
      their educational performance.

PMID- 24741653
TI  - Effect of E-learning on primigravida women's satisfaction and awareness
      concerning prenatal care.
AB  - BACKGROUND: E-learning, in addition to promotion of patients' level of awareness,
      causes a more efficient way to increase patient-personnel interaction and
      provision of patients' educational content. MATERIALS AND METHODS: In a quasi
      experimental study, 100 primigravida women, referring to Navab Safavi health care
      center affiliated to Isfahan University of Medical Sciences, were selected
      through convenient sampling. The subjects received education via E-learning or
      booklet education methods for four weeks. Questionnaire of satisfaction with the
      awareness of prenatal care was completed by both groups before and 4-6 weeks
      after education. Data were analyzed by student t-test and paired t-test through
      SPSS with a significance level of P < 0.05. RESULTS: No significant difference
      was noted between scores of satisfaction and awareness in both groups before
      education, while a significant difference was observed four weeks after
      intervention (P = 0.004). There was a significant difference between scores of
      satisfaction and awareness after intervention in both groups (P = 0.001, P =
      0.034). Satisfaction and awareness scores increased by 169% and 123%, and 61% and
      37% in the E-learning and control groups, respectively (P = 0.034). CONCLUSIONS:
      E-learning can cause an increase in the level of primigravida women's
      satisfaction and awareness. Therefore, conducting such education, as an efficient
      learning method, is recommended as it needs less time, has lower costs, and does
      not need any special equipment.

PMID- 24741654
TI  - Effectiveness of self-management promotion educational program among diabetic
      patients based on health belief model.
AB  - INTRODUCTION: Diabetes is a chronic disease; it can cause serious complications.
      Diabetes self-management is essential for prevention of disease complications.
      This study was conducted to evaluate self-management promotion educational
      program intervention efficiency among diabetic patients in Iran and health belief
      model (HBM) was applied as a theoretical framework. MATERIALS AND METHODS:
      Overall, 120 Type 2 diabetic patients referred to rural health centers in
      Gachsaran, Iran participated in this study as randomly divided into intervention
      and control group. This was a longitudinal randomized pre- and post-test series
      control group design panel study to implement a behavior modification based
      intervention to promotion self-management among diabetic patients. Cross
      tabulation and t-test by using SPSS statistical package, version 16 was used for
      the statistical analysis. RESULTS: Mean age was 55.07 years (SD = 9.94, range: 30
      70). Our result shows significant improvements in average response for
      susceptibility, severity, benefit and self-management among intervention group.
      Additionally, after intervention, average response of the barrier to self
      management was decreased among intervention group. CONCLUSION: Our result showed
      education program based on HBM was improve of self-management and seems
      implementing these programs can be effective in the and prevention of diabetes
      complications.

PMID- 24741655
TI  - Association between dietary iron, iron stores, and serum lipid profile in
      reproductive age women.
AB  - BACKGROUND: Some studies have shown that increased rate of iron stores even in a
      normal range may increase cardiovascular diseases (CVDs) in some individuals.
      Lipid disorders are also the risk factors for CVDs. Therefore, the question is
      whether or not iron store is correlated with lipid profile, this study evaluates
      the association between dietary iron, iron stores and serum lipid profiles.
      MATERIALS AND METHODS: This cross-sectional study was done on 82 healthy
      university students and university staff females in Isfahan University of Medical
      Sciences who were in reproductive age and announced their readiness to
      participate in the study. Serum ferritin concentration, components of lipid
      profile, blood glucose, and insulin were measured in all the subjects. Dietary
      intake was assessed by semi-quantitative food frequency questionnaire. Data
      analysis was done through SPSS software, version 18. RESULTS: Pearson correlation
      test showed a positive and significant correlation between serum ferritin
      concentration levels with triglyceride (r = 0.278; P = 0.006), total cholesterol
      (r = 0.267; P = 0.008), and blood glucose (r = 0.275; P = 0.006); however, the
      correlation between serum ferritin, high-density lipoprotein-cholesterol, low
      density lipoprotein-cholesterol, and insulin was not significant. After
      adjustment of confounding factors, only the significant correlation occurred for
      blood glucose (P = 0.016). Before and after adjustment of confounding factors,
      there was no significant correlation between hemoglobin and hematocrit with
      concentration of lipid profile components, glucose and insulin. Before and after
      adjustment of confounding factors, there was no significant correlation between
      total amount of iron, heme iron, and non-heme dietary iron with concentration of
      lipid profile components, glucose and insulin. CONCLUSION: According to the
      current study, serum ferritin is directly and significantly correlated with
      concentration of fasting blood glucose, which emphasized on the amount of iron
      store with blood glucose even in healthy people. The results of the present study
      indicate no significant correlation between iron store and dietary iron intake
      with lipid parameters and insulin. Conducting more extensive epidemiologic
      studies in men and other age groups is recommended.

PMID- 24741656
TI  - Comparison of the effects of povidone-iodine and chlorhexidine solutions on skin
      bacterial flora among hospitalized infants.
AB  - BACKGROUND: Infection control is an essential part of caring for hospitalized
      infants. With regard to the change of bacterial resistance over time and places,
      as well as the need for periodic studies on the effectiveness of antiseptics,
      this study aims to compare the effects of both solutions of povidone-iodine and
      chlorhexidine on skin bacterial flora among hospitalized infants. MATERIALS AND
      METHODS: This clinical trial recruited 98 hospitalized infants and each of the
      above-mentioned solutions has been applied to a small area in the left or right
      side of the infants' bodies. Skin cultures were taken before, immediately after
      and 2 h after the randomly chosen infants' skin areas that were disinfected by
      each solution (588 skin cultures in total). Colony count and determination of
      microorganism types were done by only one person in a single laboratory. The
      study has been conducted in two teaching hospitals in Isfahan, Iran. RESULTS:
      Staphylococcus epidermidis was the most common microorganism prior to skin
      disinfection by either solution. Two hours after disinfection, "Staphylococcus
      epidermidis" and "Staphylococcus epidermidis and kelebsila" had the highest
      frequencies of 3.1% and 3.1%, respectively. Before and 2 h after disinfection,
      distribution of different types of microorganisms had no significant difference
      between the two groups (P = 0.84 and 0.13, respectively); however, the difference
      was significant immediately after disinfection, P < 0.01. CONCLUSION: The present
      study demonstrated that 10% povidone-iodine solution has more significant effect
      on reduction of skin pathogens promptly after application compared to 2%
      chlorhexidine. Therefore, prior to any catheterization procedures, it is
      imperative to use 10% povidone-iodine solutions for skin disinfection.

PMID- 24741657
TI  - A comparison of substance dependence treatment information system in America,
      England, and Iran.
AB  - CONTEXT: Addiction, as a social problem, is a phenomenon that causes structural
      changes in cultural, social, political, and economic system in society.
      Prevention of this problem means decrease of risk factors and increase of
      protective factors; and recognition of these factors is possible with the help of
      update, accurate, and complete information in information systems. AIMS: The aim
      of this study was to compare substance dependence treatment information system
      (SDTIS) in America, England, and Iran. MATERIALS AND METHODS: This research was
      an applied and comparison-descriptive study, in which SDTIS was compared in
      America, England, and Iran. These countries were chosen based on available
      information on the Internet and also on the development of these countries in the
      health information management field. Information resources included library
      resources, electronic resources, and expert people (Health Information
      Management, Medical Records Education, Psychologist, Psychiatrist, and Medical
      Informatics). The data collection tool was the data raw form, whose reliability
      was proved by expert people. STATISTICAL ANALYSIS USED: Findings were analyzed by
      theory and descriptive method. RESULTS: America and England had the SDTIS. Their
      systems had special characteristics such as goals, scope, special method for
      collecting, processing, reporting, quality and validity control, and
      confidentiality principles. However, there was no such system in Iran and the
      present situation in Iran has many differences with similar situations in the
      studied countries. CONCLUSION: Presence of an information system in the substance
      dependence treatment field helps to prevent, control, and treat addicted people.
      Hence, we try to submit a suitable model for implementing this system.

PMID- 24741658
TI  - Effects of work-related stress on work ability index among refinery workers.
AB  - INTRODUCTION: Work-related stress is one of the basic problems in industrial also
      top 10 work-related health problems and it is increasingly implicated in the
      development a number of problems such as cardiovascular disease, musculoskeletal
      diseases, early retirement to employees. On the other hand, early retirement to
      employees from the workplace has increased on the problems of today's industries.
      Hereof, improving work ability is one of the most effective ways to enhance the
      ability and preventing disability and early retirement. The aim of This study is
      determine the relationship between job stress score and work ability index (WAI)
      at the refinery workers. MATERIALS AND METHODS: This is a cross-sectional study
      in which 171 workers from a refinery in isfahan in 2012 who were working in
      different occupational groups participated. Based on appropriate assignment
      sampling, 33 office workers, 69 operational workers, and 69 maintenance workers,
      respectively, were invited to participate in this study. Two questionnaires
      including work related-stress and WAI were filled in. Finally, the information
      was analyzed using the SPSS-20 and statistic tests namely, analysis of covariance
      Kruskal-Wallis test. Pearson correlation coefficient, ANOVA and t-test. RESULTS:
      Data analysis revealed that 86% and 14% of participants had moderate and severe
      stress respectively. Average score of stress and standard deviation was 158.7 +/-
      17.3 that was in extreme stress range. Average score and standard deviation of
      WAI questionnaire were 37.18 and 3.86 respectively. That placed in a good range.
      Pearson correlation coefficient showed that WAI score had significant reversed
      relationship with a score of stress. CONCLUSION: According to the results, mean
      stress score among refinery worker was high and one fator that affect work abiity
      was high stress, hence training on communication skills and safe working
      environment in order to decreses stress, enhance the work ability of workers.

PMID- 24741659
TI  - Investigating the predictive of risk-taking attitudes and behaviors among Iranian
      drivers.
AB  - BACKGROUND: World Health Organization findings shows that up to year 2020 the
      number of fatality due to driving accidents will increases up to 65%, which is
      80% is in developing countries. Iran has one of the highest rates of road traffic
      accident mortality rate in the world. MATERIALS AND METHODS: The cross-sectional
      study was carried out in the center and west of Iran upon 540 ordinary and taxi
      drivers who were driving regularly from bus terminals and the travel agencies to
      other cities. Data collection tool is a questionnaire that measuring driving risk
      taking by two items of risky driving behaviors and risk taking attitudes.
      FINDINGS: The results of this study showed that the averages of risk driving
      behaviors scores were higher than the average of risk taking attitudes scores.
      The results of logistic regression test showed that the risky driving behaviors
      can be a predictor of driving accidents due to individuals' risk taking (P =
      0.014). Among all these variables, attitude toward rule violations and speeding,
      aggressive driving and violation of the road laws respectively are important
      predictive of drivers' risk taking (P < 0.0010). DISCUSSION AND CONCLUSION:
      Although attitude toward risk taking has been located at a low level by different
      ways, a desired result was not obtained from the reduction of those high risky
      behaviors; in fact, high-rate of accidents and traffic incidence in Iran
      indicates this matter well.

PMID- 24741660
TI  - The relationship between dimensions of religiosity/spirituality with mental
      health and hope for future between staff of public hospitals in Shiraz.
AB  - INTRODUCTION: Due to the impacts of spirituality and its dimensions on
      psychological structures in the workplace and their ability to influence
      organizational performances have received a great attention in recent years.
      Thus, this study investigated the relationship between dimensions of spirituality
      with mental health and hope for future. MATERIALS AND METHODS: This is a
      correlational study with a statistical population, including public Hospital's
      personnel of Shiraz done in autumn 1389. To collect the research data, three
      different types of questionnaires were used: (1) Hope for the future (4 items),
      (2) mental health (12 items), and (3) components of religiosity/spirituality at
      (31 items and based on 5 components). Data were analyzed using Pearson's
      correlation and Hierarchical regression analysis. FINDINGS: Research findings
      show that there are significant correlations between existential well-being and
      hope for the future, motivation, devotion and coping and hope for the future, and
      mental health and hope for the future. Furthermore, all components of
      religiosity/spirituality have had significant correlations with mental health.
      Hierarchical regression analysis showed that in the first step motivation,
      devotion and coping with a variance of 5%, in the second step motivation,
      devotion and coping with mental health with a variance of 6.4%, in the third step
      motivation, devotion and coping with mental health and existential well-being
      with a variance of 9.1% and in the fourth step, the combining of motivation,
      devotion and coping and existential well-being with a variance of 8.9% with hope
      for the future have meaningful multiple relationships. CONCLUSION: Findings
      indicated that motivation, devotion and coping with existential well-being,
      respectively, were the most important dimensions of religiosity-spirituality that
      together with mental health affect hope for future. It is necessary that the
      dimension of motivation, devotion and coping, existential well-being and
      personnel mental health should be strengthened to increase the staff's hope for
      future.

PMID- 24741661
TI  - Predicting of perceived self efficacy in the amount of macronutrients intake in
      women with metabolic syndrome - 2012.
AB  - INTRODUCTION: Metabolic syndrome is a collection of metabolic disorders, which
      can increase the mortality rates from 20% to 80%. One of strategies to control
      the disease is the attention to the dietary habits. Compliance with proper diet
      is one of the major challenges in the management of this syndrome. Due to this
      fact, that the patient is responsible for the adjustment of the daily diet, it is
      important to identify the factors affecting the adoption of nutritional self
      care. Besides, self-efficacy is considered as an important pre-requisite for this
      behavior because it acts as an independent part of the basic skills. This study
      was carried out with the purpose of determining the predictive role of perceived
      self-efficacy on macronutrients intake in women with metabolic syndrome.
      MATERIALS AND METHODS: In this descriptive study with correlational nature in
      2012, there were 329 patients with the metabolic syndrome. The patients were
      covered by Isfahan oil industry medical centers and selected by a systematic
      method. In order to gather information on perceived self-efficacy, the
      questionnaires constructed by the researchers were used and the validity and
      reliability had been confirmed by the calculation of content validity indexand
      content validity ratio values and the indices of internal consistency and
      stability of the tool. The 24-h dietary recall questionnaire was also used for 3
      days in order to investigate the nutritional behavior. The obtained data from the
      dietary recall questionnaire were analyzed by the N4 nutritional software. In
      this study, AMOS software version 16 was used for the structural model fitting by
      using the generalized least squares method besides the SPSS statistical software
      version 16. RESULTS: THESE AVERAGES OBTAINED FROM THE RESULTS: 2512.37 kcal
      energy intake, 70.95 g protein, 420 g carbohydrates and 61.61 g of fat per day.
      The mean of perceived self-efficacy score was 47.89. The Pearson correlation
      coefficient was indicated a significant inverse relationship between the
      perceived self-efficacy and intake of macronutrients in the metabolic syndrome.
      The most direct effect of the coefficient of perceived self-efficacy was observed
      on fat and carbohydrate intake (P < 0.05 and beta = -0.592) and (P < 0.05 and
      beta = -0.395). CONCLUSIONS: The amount of energy, carbohydrate, fat and protein
      were more than the recommended dietary allowances levels and the amount of self
      efficacy was moderate. The present study showed that perceived self-efficacy
      provided a useful framework to understand and predict adherence to dietary self
      care behaviors in patients with metabolic syndrome.

PMID- 24741662
TI  - Comparison of satisfactions from mastectomy and Lump Ectome in breast cancer
      patients.
AB  - INTRODUCTION: The prevalence of breast cancer among women in compare to other
      types of cancers in all over the world and in Iran is high. Mastectomy surgery is
      one of the common treatments for these patients. Another method, which is less
      invasive, is Lumpectomy. This study comprised the satisfaction of patients under
      two types of surgery; Mastectomy and Lumpectomy. MATERIALS AND METHODS: In this
      cross-sectional study, two types of patients which had either, Mastectomy or
      Lumpectomy, were studied. RESULTS: From 119 patients which studied here, 80
      patients (66.7%) were treated by mastectomy and 39 patients (32.5%) were treated
      under lumpectomy. Two groups had not significant differences in duration between
      diagnostic and surgery, the number of lymph nodes involved and the number of
      lymph nodes removed. Lumpectomy patients had higher pain and numbness in 24 h, 1
      week after surgery and at the time of study than the other group. The observed
      difference was significant (P = 0.043). DISCUSSION: It is implied in previous
      studies that patients under lumpectomy had more satisfaction than patients under
      mastectomy. However, no differences were observed in quality-of-life between the
      two groups in some other studies. The differences between various studies might
      be for the sake of cultural variety and time interval between surgery and filling
      questionnaire.

PMID- 24741663
TI  - Factors affecting cigarette smoking based on health-belief model structures in
      pre-university students in Isfahan, Iran.
AB  - INTRODUCTION: The goal of this study was to determine the association between
      constructs of the Health Belief Model (HBM) (i.e., perceived susceptibility to
      health-related problems due to smoking, perceived barriers to non-smoking,
      perceived benefits of non-smoking, perceived self-efficacy to non-smoking, and
      cues to action of non-smoking) and cigarette smoking among male pre-college
      students. MATERIALS AND METHODS: A cross-sectional survey of 382 pre-college
      students was conducted in Isfahan, in 2010. The method of sampling was systematic
      randomized and students were selected from eight schools. The instrument was
      developed by the researchers based on the Health Belief Model. Statistical
      analyses were carried out using SPSS.V.18, Chi-square, and independent t-tests.
      RESULTS: The mean age of the students was 17.72 +/- 0.62 years. Overall 7.2% of
      the subjects reported having smoked in the past 30 days and 32.7% % of the
      samples reported ever having smoked in their life time. Results of the t-test
      showed that there were significant differences in knowledge, perceived
      susceptibility (P =0.03), benefits (t (246) = -2.51, P =0.01), self-efficacy (P <
      0.001), and cues to action (P = 0.007), between smokers and non-smokers.
      CONCLUSION: These results suggested that the constructs of HBM can be
      incorporated when examining the predictors of cigarette smoking and developing
      smoking prevention programs among pre-college students. Furthermore, with a
      better understanding of the factors affecting this complex behavior (cigarette
      smoking), it can be a useful step to reduce the rate of death, costs, and also
      improve the community health outcomes.

PMID- 24741664
TI  - The relationship between emotional intelligence health and marital satisfaction:
      A comparative study.
AB  - INTRODUCTION: Marriage is known as the most important incident in everyone's life
      after birth. The most important purpose of marriage is achieving a life followed
      with love and affection beside the spouse and providing mental comfort and
      general health. The aim of the present study is to investigate the relationship
      between emotional intelligence health and marital satisfaction among married
      people. MATERIALS AND METHODS: The research method is descriptive- analytic and
      its design is comparative, done on 226 people including 114 persons (50 women and
      64 men) having marital conflicts, and 112 people (58 women and 54 men) having
      marital satisfaction, by cluster random sampling from 13 districts of the city of
      Isfahan. Bar-on (with 90 questions) and Enrich marital satisfaction (115
      questions) questionnaires were used for collecting the required information. The
      data was analyzed using descriptive statistics including independent t-tests,
      Pearson correlation, and linear regression analysis, using SPSS software version
      19. RESULTS: The results from the research showed that the scores of emotional
      intelligence in married people group having marriage conflicts who had referred
      to the administration of justice was 57.3 +/- 13.2, and the random sample from
      the married people in the city of Isfahan as the comparing group had the score of
      67.2 +/- 9.5, and the difference of the average scores for the emotional
      intelligence for the two groups was significant (P < 0.001). The correlation
      analysis showed that there was a significant and positive relation between
      emotional intelligence and marital satisfaction (P < 0.001, r = 0.529). The
      results of linear regression also showed that the general emotional intelligence
      predicts the quality of marital satisfaction. The emotion of the predicting line
      of the marital satisfaction score (y) is in the form of: y = 14.8 + 0.656x, by
      using the emotional intelligence score (x). CONCLUSION: Regarding the close
      relations between emotional intelligence and marital satisfaction, education
      centers such as universities, organizations and family clinics could use this
      variable in micro- and macro-social plans for improving the quality of the
      married people relations and promoting health of the families and the society.

PMID- 24741665
TI  - Physical activity patterns and its influencing factors among high school students
      of Izeh city: Application of some constructs of health belief model.
AB  - PURPOSE: This study has been conducted to identify the roles of self-efficacy,
      benefits of and barriers to physical activity, and its relationship with physical
      activity in male and female high school students in the city of Izeh, Iran.
      MATERIALS AND METHODS: In this cross-sectional descriptive analytical study, 500
      students (200 boys and 300 girls) from high schools of Izeh city during the
      period 2011-2012 were chosen using the multistage random sampling method. The
      data for this study was acquired through a multisectional questionnaire that
      included sections as follows: Demographic characteristics, self-efficacy, and
      perceived benefits and barriers. The gathered data was then studied and analyzed.
      Statistical tests such as independent t-tests, Spearman's correlation, Pearson's
      correlation coefficient and linear regression were used to interpret and analyze
      the data. RESULTS: Data analysis showed that the mean age of male participants
      was 15.67 +/- 0.95 years and females 15.86 +/- 1.16 years. The average weekly
      time of physical activity in male students was 424.74 +/- 158.48 min and in
      females 186.63 +/- 90.59 min. The mean scores for self-efficacy and perceived
      benefits of physical activity were significantly higher in boys as compared to
      girls. There was a positive and significant correlation between the mean scores
      for perceived self-efficacy and the weekly time in male students spent on
      physical activity as well as the mean scores for perceived benefits and the
      weekly time spent on physical activity in both genders. CONCLUSION: The results
      of this study showed that many factors influence students' physical activity;
      however, the role of these factors is not identical in the two genders. An
      understanding of these factors helps educationalists and other health experts
      design appropriate interventions.

PMID- 24741666
TI  - Microbial Reverse-Electrodialysis Electrolysis and Chemical-Production Cell for
      H2 Production and CO2 Sequestration.
AB  - Natural mineral carbonation can be accelerated using acid and alkali solutions to
      enhance atmospheric CO2 sequestration, but the production of these solutions
      needs to be carbon-neutral. A microbial reverse-electrodialysis electrolysis and
      chemical-production cell (MRECC) was developed to produce these solutions and H2
      gas using only renewable energy sources (organic matter and salinity gradient).
      Using acetate (0.82 g/L) as a fuel for microorganisms to generate electricity in
      the anode chamber (liquid volume of 28 mL), 0.45 mmol of acid and 1.09 mmol of
      alkali were produced at production efficiencies of 35% and 86%, respectively,
      along with 10 mL of H2 gas. Serpentine dissolution was enhanced 17-87-fold using
      the acid solution, with approximately 9 mL of CO2 absorbed and 4 mg of CO2 fixed
      as magnesium or calcium carbonates. The operational costs, based on mineral
      digging and grinding, and water pumping, were estimated to be only $25/metric ton
      of CO2 fixed as insoluble carbonates. Considering the additional economic
      benefits of H2 generation and possible wastewater treatment, this method may be a
      cost-effective and environmentally friendly method for CO2 sequestration.

PMID- 24741668
TI  - Ultrasensitive colorimetric detection of Cu2+ using gold nanorods.
AB  - We utilized Cu(2+) induced gold nanorod shortening in the presence of Na2S2O3 and
      NH3 for colorimetric sensing of copper ions. Compared with conventional methods,
      this method has good reproducibility, fast response time and very high
      sensitivity to Cu(2+). The sensor has a large dynamic range for Cu(2+) covering 5
      nM to 500 mM with a detection limit of 1.6 nM, which is lower than previously
      reported for the colorimetric detection of copper ions. 

PMID- 24741667
TI  - (-)-Epicatechin protects hemorrhagic brain via synergistic Nrf2 pathways.
AB  - OBJECTIVE: In the wake of intracerebral hemorrhage (ICH), a devastating stroke
      with no effective treatment, hemoglobin/iron-induced oxidative injury leads to
      neuronal loss and poor neurologic outcomes. (-)-Epicatechin (EC), a brain
      permeable flavanol that modulates redox/oxidative stress via the NF-E2-related
      factor (Nrf) 2 pathway, has been shown to be beneficial for vascular and
      cognitive function in humans. Here, we examined whether EC can reduce early brain
      injury in ICH mouse models and investigated the underlying mechanisms. METHODS:
      ICH was induced by injecting collagenase, autologous blood, or thrombin into
      mouse striatum. EC was administered orally at 3 h after ICH and then every 24 h.
      Lesion volume, neurologic deficits, brain edema, reactive oxygen species, and
      protein expression and activity were evaluated. RESULTS: EC significantly reduced
      lesion volume and ameliorated neurologic deficits in both male and female ICH
      mice. Cell death and neuronal degeneration were decreased in the perihematomal
      area and were associated with reductions in caspase-3 activity and HMGB-1 level.
      These changes were accompanied by attenuation of oxidative insults, increased
      phase II enzyme expression, and increased Nrf2 nuclear accumulation.
      Interestingly, in addition to providing neuroprotection via Nrf2 signaling, EC
      diminished heme oxygenase-1 induction and brain iron deposition via an Nrf2
      independent pathway that downregulated ICH-induced activating protein-1
      activation and decreased matrix metalloproteinase 9 activity, lipocalin-2 levels,
      iron-dependent cell death, and ferroptosis-related gene expression.
      INTERPRETATION: Collectively, our data show that EC protects against ICH by
      activation of Nrf2-dependent and -independent pathways and may serve as a
      potential intervention for patients with ICH.

PMID- 24741669
TI  - Deposition of luminescent Y2O3:Eu3+ on ferromagnetic mesoporous CoFe2O4@mSiO2
      nanocomposites.
AB  - Luminescent Y2O3:Eu(3+) particles have been deposited on the surface of
      ferromagnetic mesoporous CoFe2O4@mSiO2 nanoparticles by a co-precipitation
      method, obtaining multifunctional CoFe2O4@mSiO2@Y2O3:Eu(3+) nanocomposites. XRD,
      SEM, TEM, EDX, XPS, N2-adsorption-desorption, FT-IR, VSM and PL were used to
      characterized the samples. The results reveal that the nanocomposites display
      typical mesoporous characteristics with high surface areas (BET), large pore
      volumes and core-shell structures. The composites show ferromagnetic properties
      and red luminescence from the (5)D0-(7)F2 transition at 610 nm. The size and the
      magnetic and luminescence properties of the composites could be tuned by
      systematically varying the experimental parameters, such as the annealing
      temperature, the mass ratio of CoFe2O4@mSiO2 to Y2O3:Eu(3+), and the volume of
      TEOS. A possible quenching mechanism of the luminescent Y2O3:Eu(3+) by the
      ferromagnetic CoFe2O4 is proposed. The high BET and large pore volume may give
      the composite potential application in controlled drug release. 

PMID- 24741670
TI  - Exploring the nature of interactions among thiophene, thiophene sulfone,
      dibenzothiophene, dibenzothiophene sulfone and a pyridinium-based ionic liquid.
AB  - In order to gain an understanding of the nature of the interactions among
      thiophene (TS), thiophene sulfone (TSO2), dibenzothiophene (DBT),
      dibenzothiophene sulfone (DBTO2) and the ionic liquid N-butylpyridinium hydrogen
      sulfate ([BPY][HSO4]), a systematic investigation has been carried out using ab
      initio methods. The most stable structures indicate that both [BPY](+) and
      [HSO4](-) play crucial roles in the interactions between TS, TSO2, DBT, DBTO2 and
      [BPY][HSO4]. Analyses of the most stable optimized structures suggest the
      occurrence of steric effects, pi-pi stacking effects, hydrogen bonds, and
      dihydrogen bonds. The pi-pi stacking effect in [BPY][HSO4]-TSO2/[BPY][HSO4]-DBTO2
      is less significant than that in [BPY][HSO4]-TS/[BPY][HSO4]-DBT, as TSO2 and
      DBTO2 are more nucleophilic than TS and DBT, resulting in stronger interactions
      between [BPY][HSO4] and TSO2/DBTO2 than between [BPY][HSO4] and TS/DBT.
      Thermodynamical data also demonstrate that TSO2/DBTO2 are more prone to interact
      with [BPY][HSO4] compared with TS/DBT. 

PMID- 24741672
TI  - Reversible potentials for steps in methanol and formic acid oxidation to CO2;
      adsorption energies of intermediates on the ideal electrocatalyst for methanol
      oxidation and CO2 reduction.
AB  - Quantum chemical theory is used to identify the reasons for platinum's
      limitations as an electrocatalyst for oxidizing methanol at fuel cell anodes. The
      linear Gibbs energy relation (LGER) method is employed to predict reversible
      potentials for reaction steps for intermediates on the electrode surface. In this
      procedure, standard reversible potentials are calculated for the reactions in
      bulk solution phase and then they are perturbed using calculated adsorption bond
      strengths to the electrode surface, yielding the equilibrium potentials for each
      electron transfer step for adsorbed intermediates. Adsorption properties of ideal
      electrocatalysts for the methanol oxidation are found by imposing the condition
      that the reversible potential of each electron transfer step equals that for the
      overall reaction. The adsorption bond strengths that provide the ideal properties
      also apply to formic acid oxidation and carbon dioxide reduction. It is
      instructive to think of the ideal electrocatalyst as a lens that focusses the
      reversible potentials for the n individual electron transfer steps to the
      reversible potential for the n-electron process. It is found that the ideal
      catalyst will adsorb many intermediates, including HOOC, CO, OCH, HOC, HOCH,
      HOCH2, and OCH3 more weakly than platinum, and OOCH and OH more strongly. For
      example, for one possible pathway it is necessary to weaken adsorption bond
      strengths for HOCH2, HOCH, OCH, HOOC by about 0.5 eV, weaken adsorption CO by
      about 1.1 eV and strengthen OH adsorption by about 0.6 eV. These results imply a
      need for developing new multi-component catalysts. 

PMID- 24741671
TI  - Multipolar electrostatics.
AB  - Atomistic simulation of chemical systems is currently limited by the elementary
      description of electrostatics that atomic point-charges offer. Unfortunately, a
      model of one point-charge for each atom fails to capture the anisotropic nature
      of electronic features such as lone pairs or pi-systems. Higher order
      electrostatic terms, such as those offered by a multipole moment expansion,
      naturally recover these important electronic features. The question remains as to
      why such a description has not yet been widely adopted by popular molecular
      mechanics force fields. There are two widely-held misconceptions about the more
      rigorous formalism of multipolar electrostatics: (1) Accuracy: the implementation
      of multipole moments, compared to point-charges, offers little to no advantage in
      terms of an accurate representation of a system's energetics, structure and
      dynamics. (2) Efficiency: atomistic simulation using multipole moments is
      computationally prohibitive compared to simulation using point-charges. Whilst
      the second of these may have found some basis when computational power was a
      limiting factor, the first has no theoretical grounding. In the current work, we
      disprove the two statements above and systematically demonstrate that multipole
      moments are not discredited by either. We hope that this perspective will help in
      catalysing the transition to more realistic electrostatic modelling, to be
      adopted by popular molecular simulation software. 

PMID- 24741673
TI  - Effect of fluorine substitution on structures and reactivity of Keggin-Al13 in
      aqueous solution: an exploration of the fluorine substitution mechanism.
AB  - The structures and reactivity of fluoridated Keggin-aluminum tridecamers (K-Al13)
      in aqueous solution were studied using density functional theory (DFT) in order
      to explore the fluorine substitution process and the influence of F(-) on the
      chemical behavior of Keggin polynuclear Al species. The structures of fluoridated
      K-Al13 were optimized with the consideration of both explicit and bulk solvent
      effects. The obtained optimization parameters indicate that the fluorine
      substitution on distinct sites results in the different structural changes. The
      consistency between the computational and experimental (19)F and (27)Al NMR
      chemical shifts validates the suitable computational method for the present
      clusters. According to the computed energy barriers of water exchange reactions,
      it was found that the reactivity of eta-OH2 decreases as a function of fluorine
      bridges. The appearance of fluorine bridges does not change the dissociative
      activated mechanism, but the larger dissociative trend was observed. Combining
      the present computational results with previous experimental observations, we
      reasonably put forward the fluorine substitution process and attempt to interpret
      the experimental phenomenon concerned at the molecular scale and further reveal
      the mechanism of F(-) promoting dissolution of mineral. 

PMID- 24741674
TI  - Removal of Congo Red by magnetic mesoporous titanium dioxide-graphene oxide core
      shell microspheres for water purification.
AB  - Magnetic mesoporous titanium dioxide-graphene oxide (Fe3O4@mTiO2@GO) with a large
      surface area and a good magnetic responsiveness was synthesized by immobilizing a
      mesoporous titanium dioxide (mTiO2) shell on the surface of magnetic Fe3O4
      nanoparticles prior to binding with graphene oxide (GO). It showed a tunable pore
      structure and surface properties, and was mechanically strong. The characteristic
      results of a Fourier transform infrared spectrometer (FTIR), a scanning electron
      microscope (SEM), a vibrating sample magnetometer (VSM) and X-ray diffraction
      (XRD) indicated that Fe3O4@mTiO2@GO has been prepared. Fe3O4@mTiO2@GO was used as
      an adsorbent for the removal of Congo Red (CR) from simulated wastewater with a
      fast solid-liquid separation in the presence of an external magnetic field. Batch
      adsorption experiments were performed to evaluate the adsorption conditions and
      reusability. The results showed that the maximum adsorption capacity was 89.95 mg
      g(-1), which is much higher than the previously reported values of other
      absorbent materials. Moreover, the Fe3O4@mTiO2@GO could be repeatedly used via
      simple treatment without any obvious structure and performance degradation. The
      adsorption kinetic data were best described by a pseudo-second-order model and
      the equilibrium adsorptions were well-described by the Freundlich isotherm model.
      The Fe3O4@mTiO2@GO may be suitable materials for use in CR pollution cleanup if
      synthesized on a large scale and at a low price in the near future. 

PMID- 24741675
TI  - Metal(II) complexes synthesized based on quinoline-2,3-dicarboxylate as
      electrocatalysts for the degradation of methyl orange.
AB  - Based on quinoline-2,3-dicarboxylic acid (H2L), two metal(II) complexes
      formulated as MnL(phen)(H2O).H2O (phen = 1,10-phenanthroline) (1) and
      Co(HL)2(PPA).4H2O (PPA = N(1),N(4)-di(pyridin-4-yl)terephthalamide) (2) were
      synthesized and structurally characterized by single-crystal X-ray diffraction.
      Both complexes 1 and 2 exhibit one-dimensional (1D) chain-like structures, in
      which stable five-membered rings are observed. Different chains are linked by
      strong pi-pi stacking interactions into a three-dimensional (3D) supramolecular
      architecture. Both complexes can increase the degradation rate of methyl orange
      (MO), which is expected to be associated with their electrocatalytic activities
      for the H2 evolution reaction from water.

PMID- 24741676
TI  - Solvothermal synthesis of orthorhombic Sb2WO6 hierarchical structures and their
      visible-light-driven photocatalytic activity.
AB  - We report the solvothermal synthesis of hierarchical structures of orthorhombic
      Sb2WO6 and their implementation as a visible-light-driven photocatalyst for the
      degradation of Rhodamine B. The obtained hierarchical structures constructed by
      tiny nanosheets are doughnut-like flat ellipsoids with concaves in the centres,
      and with typical sizes of 1.3 MUm in length, 800 nm in width and 400 nm in
      thickness. The concave characteristics and sizes of Sb2WO6 hierarchical
      structures can be tuned by adjusting the volume ratio of EG-H2O. Time-dependent
      experiments reveal that the formation process of concave structures involves the
      aggregation of nanoparticles to form solid spheres, dissolution-recrystallization
      to form hierarchical structures subsequently, and an Ostwald ripening process to
      shape the desired concaves finally. Under visible-light irradiation, complete
      degradation of Rhodamine B is achieved within 180 min in the presence of Sb2WO6
      hierarchical structures, which could be ascribed to the porous structures, high
      BET surface area (42.58 m(2) g(-1)) and wide absorption in the visible-light
      region. 

PMID- 24741677
TI  - Disaggregation of heteroaggregates composed of multiwalled carbon nanotubes and
      hematite nanoparticles.
AB  - In this study, the disaggregation behavior and the strength of heteroaggregates
      composed of multiwalled carbon nanotubes (CNTs) and hematite nanoparticles
      (HemNPs) were investigated in different solution chemistries. Negatively charged
      CNTs and positively charged HemNPs were first allowed to undergo favorable
      heteroaggregation at pH 5.5 and 0.1 mM NaCl before the CNT-HemNP heteroaggregates
      were disaggregated through the use of an ultrasonication bath. The
      heteroaggregate sizes before and after ultrasonication were measured by dynamic
      light scattering (DLS) in order to determine the degree of disaggregation. When
      the solution chemistry was unchanged, the heteroaggregates underwent partial
      disaggregation and heteroaggregate re-growth was observed after ultrasonication.
      Conversely, when the pH was raised to 11.0 immediately before ultrasonication,
      the heteroaggregates were almost completely disaggregated and no aggregation took
      place after disaggregation. Similarly, the introduction of humic acid led to a
      near complete disaggregation of the CNT-HemNP heteroaggregates. The elevated pH,
      as well as the adsorption of humic acid on the nanoparticles, was likely to
      weaken the particle-particle bonds within the heteroaggregates and hence increase
      the propensities of the heteroaggregates to undergo disaggregation. 

PMID- 24741678
TI  - Soy lipophilic protein nanoparticles as a novel delivery vehicle for conjugated
      linoleic acid.
AB  - Soy lipophilic protein nanoparticles (LPP), which present a novel delivery
      vehicle for conjugated linoleic acid (CLA), were fabricated by ultrasonication of
      the soy lipophilic protein (LP), which exhibits unique characteristics including
      a high loading capacity, oxidation protection and a sustained releasing profile
      in vitro for CLA. The CLA-loaded LPP exhibited a mean diameter of 170 +/- 0.63 nm
      and a loading capacity of 26.3 +/- 0.40% (w/w). A coating of sodium caseinate
      (SC) on the surface improved the colloidal stability of the CLA-loaded LPP. This
      encapsulation conferred protection against the oxidation of CLA, by which the
      head space-oxygen consumption and hydrogen peroxide value were obviously
      decreased in comparison with the SC-encapsulated CLA and CLA alone. The delivery
      system enables a sustained releasing profile of CLA in a simulated
      gastrointestinal tract (GIT). These findings illustrate that the LPP could act as
      an effective delivery device for CLA, which could provide oxidation stability and
      a sustained release property. 

PMID- 24741679
TI  - Fabrication of coated bovine serum albumin (BSA)-epigallocatechin gallate (EGCG)
      nanoparticles and their transport across monolayers of human intestinal
      epithelial Caco-2 cells.
AB  - The bovine serum albumin (BSA)-epigallocatechin gallate (EGCG) nanoparticles were
      fabricated using a desolvation method, and coated with poly-epsilon-lysine or
      chitosan. BSA-EGCG nanoparticles (BEN), poly-epsilon-lysine coated BSA-EGCG
      nanoparticles (PBEN), and chitosan coated BSA-EGCG nanoparticles (CBEN) had a
      spherical morphology and a size of 186, 259, and 300 nm, respectively. The
      loading efficiency of EGCG in these nanoparticles was 32.3%, 35.4%, and 32.7%,
      whereas the loading capacity was 18.9%, 17.0%, and 16.0% (w/w), respectively.
      Poly-epsilon-lysine or chitosan coating prevented the aggregation of
      nanoparticles at pH 4.5-5.0. However, they caused particle aggregation at pH 6.5
      7.0. BEN had negative zeta-potentials between pH 4.5 and 6.0. Poly-epsilon-lysine
      or chitosan coating changed the zeta-potentials to positive. The release study of
      EGCG from the nanoparticles in the simulated gastric or intestinal fluid with or
      without digestive enzymes showed that poly-epsilon-lysine and chitosan coatings
      delayed EGCG release from the nanoparticles. Poly-epsilon-lysine or chitosan
      coating improved the stability of EGCG during storage at 60  degrees C compared
      with EGCG in the uncoated particles. EGCG in BEN, PBEN, and CBEN had a decreasing
      apparent permeability coefficient (Papp) on Caco-2 monolayers, whereas pure EGCG
      showed relatively stable Papp during the incubation over time. EGCG in CBEN
      showed significantly higher Papp, suggesting that chitosan coated BSA-EGCG
      nanoparticles may improve the absorption of EGCG. 

PMID- 24741680
TI  - All metal nanoelectromechanical switch working at 300  degrees C for rugged
      electronics applications.
AB  - An all metal based electrostatic nanoelectromechanical switch has been fabricated
      using a one mask process. High temperature cycling behavior is demonstrated in a
      vacuum chamber at 300  degrees C for more than 28 hours. The compelling results
      indicate that the design is promising for the realization of rugged electronics
      with three-dimensional integration. 

PMID- 24741681
TI  - Gene therapy to ameliorate tendinopathy-associated symptoms and pain.

PMID- 24741682
TI  - Paradoxical worsening of anti-myelin-associated glycoprotein polyneuropathy
      following rituximab.

PMID- 24741683
TI  - Are multifocal motor neuropathy patients underdiagnosed? An epidemiological
      survey in Japan.
AB  - INTRODUCTION: Our objective was to do an epidemiologic survey of patients with
      multifocal motor neuropathy (MMN) in comparison with those with amyotrophic
      lateral sclerosis (ALS) in Japan. METHODS: In this retrospective study, we
      examined 46 patients with MMN and 1,051 patients with ALS from major
      neuromuscular centers in Japan from 2005 to 2009. Diagnosis was based on the
      European Federation of Neurological Societies/Peripheral Nerve Society (EFNS/PNS)
      and the revised El Escorial criteria. The efficacy of intravenous immunoglobulin
      (IVIg) was also taken into consideration in the diagnosis of MMN. RESULTS: The
      ratio of MMN to ALS patients (0-0.10) varied among the centers, but mostly
      converged to 0.05. The prevalence was estimated to be 0.29 MMN patients and 6.63
      ALS patients per 100,000 population. CONCLUSIONS: The frequency of MMN patients
      was around 1 out of 20 ALS patients, and MMN was possibly underdiagnosed in some
      centers.

PMID- 24741684
TI  - Muscle conduction velocity, surface electromyography variables, and echo
      intensity during concentric and eccentric fatigue.
AB  - INTRODUCTION: Concentric (CON) and eccentric (ECC) contractions may involve
      different mechanisms related to changes in sarcolemma status and the consequent
      alteration of action potential transmission along muscle fibers. METHODS: Muscle
      conduction velocity (CV), surface electromyography signal (sEMG), muscle quality,
      and blood lactate concentrations were analyzed during CON and ECC actions.
      RESULTS: Compared with ECC, the CON protocol resulted in greater muscle force
      losses, blood lactate concentrations, and changes in sEMG parameters. Similar
      reductions in CV were detected in both protocols. Higher echo intensity values
      were observed 2 days after ECC due to greater muscle damage. CONCLUSIONS: The
      effects of the muscle damage produced by ECC exercise on the transmission of
      action potentials along muscle fibers (measured as the CV) may be comparable with
      the effects of hydrogen accumulation produced by CON exercise (related to greater
      lactate concentrations), which causes greater force loss and change in other sEMG
      variables during CON than during ECC actions.

PMID- 24741685
TI  - Innervation zone locations in 43 superficial muscles: toward a standardization of
      electrode positioning.
AB  - INTRODUCTION: We describe the innervation zone (IZ) location in 43 muscles to
      provide information for appropriate positioning of bipolar electrodes for
      clinical and research applications. METHODS: The IZ was studied in 40 subjects
      (20 men and 20 women) using multichannel surface electromyography (sEMG). Signal
      quality was checked visually to identify motor unit action potentials and
      estimate muscle fiber conduction velocity. RESULTS: Results in 33 muscles were
      classified as excellent or good, because it was possible to identify an area
      which is favorable for appropriate positioning of an electrode pair without the
      need to previously determine the IZ location. CONCLUSIONS: Knowledge of IZ
      location will increase standardization and repeatability of sEMG measures.

PMID- 24741686
TI  - An academic-community partnership to address the flu vaccination rates of the
      homeless.
AB  - OBJECTIVE: The objective of this pilot research study was to explore the beliefs
      and barriers to flu vaccination from a sample homeless population in a small
      metropolitan community. DESIGN AND SAMPLE: In a collaborative academic-community
      partnership of a university undergraduate nursing education program, a local
      health department, and nonprofit agencies, a social marketing education program
      was developed by nursing students which included surveying the homeless for
      perceptions regarding flu vaccinations. There were a total of 87 homeless
      subjects that were surveyed. MEASURES: The measurements were obtained from
      various questions regarding flu vaccinations on a Qualtrics survey examining the
      barriers, beliefs, and practices of the homeless population. The focus addressed
      health disparities and barriers with nursing students serving as the catalyst to
      reach the homeless in an educational service-learning project. RESULTS: This
      project demonstrated a positive impact in meeting health care needs of homeless
      persons as the rate of flu vaccination was doubled from the previous year at one
      community day shelter. CONCLUSIONS: Nursing students developed their ability to
      impact a hard-to-reach population with positive changes in their attitudes by
      increased understanding of the health needs of the homeless.

PMID- 24741687
TI  - Medication usage patterns for headache treatment after mild traumatic brain
      injury.
AB  - OBJECTIVE: To describe patient self-report of headache treatment in the first
      year following mild traumatic brain injury (TBI). BACKGROUND: An understanding of
      appropriate management of symptoms after mild TBI is crucial for improving acute
      care and long-term outcomes. This is particularly true for post-traumatic
      headaches as recent studies suggest that headaches after mild TBI are common with
      multiple phenotypes. In addition, symptoms such as headache after mild TBI are
      often managed by primary care providers without specialty training, and often in
      medically underserved areas. Outside of previous opinion papers, few studies have
      guided the treatment or examined the effectiveness of the interventions for post
      traumatic headache. METHODS: One hundred sixty-seven participants admitted to a
      level 1 trauma hospital with mild TBI who were prospectively enrolled and
      reported new or worse headache at 3, 6, or 12 months after injury. RESULTS:
      Participants were primarily male (75%), white (75%), injured in vehicle crashes
      (62%), and had completed high school (83%). The majority of headaches met
      International Classification of Headache Disorders-2nd edition criteria for
      migraine/probable migraine, followed by tension-type headache. Despite the
      diverse nature of headaches, more than 70% of those with headache at each time
      period used acetaminophen or a nonsteroidal anti-inflammatory drug for headache
      control. Only 8% of those with the migraine/probable migraine phenotype used
      triptans. Of those individuals who used medication, 26% of those with
      migraine/probable migraine phenotype and 70% of those with tension headache
      phenotype endorsed complete relief (vs partial or no relief) because of
      medication use. The majority of individuals with tension headache reported never
      taking medication. CONCLUSIONS: Headaches after mild TBI are frequent and are not
      optimally treated. Results suggest that many individuals with mild TBI may be
      self-treating their headaches by utilizing over-the-counter pain relief
      medications. These medications, however, are only providing effective treatment
      for a minority of this population. Further research must be conducted to develop
      evidence-guided treatment and educate providers.

PMID- 24741689
TI  - Stimulators for the treatment of headache.

PMID- 24741688
TI  - One-day behavioral intervention in depressed migraine patients: effects on
      headache.
AB  - OBJECTIVE: To determine whether a 1-day behavioral intervention, aimed at
      enhancing psychological flexibility, improves headache outcomes of migraine
      patients with comorbid depression. BACKGROUND: Migraine is often comorbid with
      depression, with each disorder increasing the risk for onset and exacerbation of
      the other. Managing psychological triggers, such as stress and depression, may
      result in greater success of headache management. METHOD: Sixty patients with
      comorbid migraine and depression were assigned to a 1-day Acceptance and
      Commitment Training plus Migraine Education workshop (ACT-ED; N = 38) or to
      treatment as usual (TAU; N = 22). Patients completed a daily headache diary prior
      to, and for 3 months following, the intervention. Clinical variables examined
      included headache frequency/severity, medication use, disability, and visit to a
      health care professional. Comparisons were made between baseline findings and
      findings at the 3-month follow up. RESULTS: Participants assigned to the ACT-ED
      condition exhibited significant improvements in headache frequency, headache
      severity, medication use, and headache-related disability. In contrast, the TAU
      group did not exhibit improvements. The difference in headache outcomes between
      ACT-ED and TAU was not statistically significant over time (ie, the treatment by
      time interaction was nonsignificant). These results complement those of a
      previous report showing effects of ACT-ED vs TAU on depression and disability.
      CONCLUSION: A 1-day ACT-ED workshop targeting psychological flexibility may
      convey benefit for patients with comorbid migraine and depression.These pilot
      study findings merit further investigation using a more rigorously designed large
      scale trial.

PMID- 24741690
TI  - Improving health: structure and agency in health interventions.
AB  - Taking debates about the roles of structure and agency in health as a lens, this
      essay asks how Critical Realist and Feminist Intersectional approaches might
      inform health interventions research. Despite recognition of multiple
      determinants of health, health problems are often thought of as individual and
      interventions, in turn, target risky individual behaviours. Such approaches are
      rooted in a liberal model of personhood. This paper critiques enduring
      individualist assumptions linked to Western liberal underpinnings embedded in
      health interventions. It posits the need to include a robust conception of the
      social world in which change depends on shifting power relations, and individual
      agency is shaped by power as well as individual will. We propose preliminary
      steps for undertaking critical realist intersectional interventions research.

PMID- 24741691
TI  - Ruptured thought: rupture as a critical attitude to nursing research.
AB  - In this paper, we introduce the notion of 'rupture' from the French philosopher
      Michel Foucault, whose studies of discourse and governmentality have become
      prominent within nursing research during the last 25 years. We argue that a
      rupture perspective can be helpful for identifying and maintaining a critical
      potential within nursing research. The paper begins by introducing rupture as an
      inheritance from the French epistemological tradition. It then describes how
      rupture appears in Foucault's works, as both an overall philosophical approach
      and as an analytic tool in his historical studies. Two examples of analytical
      applications of rupture are elaborated. In the first example, rupture has
      inspired us to make an effort to seek alternatives to mainstream conceptions of
      the phenomenon under study. In the second example, inspired by Foucault's work on
      discontinuity, we construct a framework for historical epochs in nursing history.
      The paper concludes by discussing the potential of the notion of rupture as a
      response to the methodological concerns regarding the use of Foucault-inspired
      discourse analysis within nursing research. We agree with the critique of Cheek
      that the critical potential of discourse analysis is at risk of being undermined
      by research that tends to convert the approach into a fixed method.

PMID- 24741692
TI  - Lonergan's philosophy as grounding for cross-disciplinary research.
AB  - Increasingly, nurses conduct scientific inquiry into complex health-care problems
      by collaborating on teams with researchers from other highly specialized fields.
      As cross-disciplinary research proliferates and becomes institutionalized
      globally, researchers will increasingly encounter the need to integrate their
      particular research perspectives within inquiries without sacrificing the
      potential contributions of their discipline-specific expertise. The work of the
      philosopher Bernard Lonergan (1904-1984) offers the necessary philosophical
      grounding. Here, I defend a role for philosophy in cross-disciplinary research
      and present selected ideas in Lonergan's work. These include: (1) a dynamic,
      normative pattern that each inquirer operates uniquely also forms the common
      core, or unity, in knowing; (2) the possibility of cross-disciplinary knowledge
      development is dependent on each researcher's consciousness of her or his
      attentiveness, intelligence, reasonableness, and responsibleness; and (3) shifts
      in researchers' viewpoints, or horizons, facilitate their collaborative inquiry
      and their grasp of the unity in knowing. The desire to know, shared by team
      members, drives their inquiry. Lonergan's stance is consistent with nursing
      values because it respects, but does not unconditionally privilege, any
      researcher or discipline. Arguments support a claim that Lonergan's perspective
      is well suited to guide nurse researchers participating on cross-disciplinary
      health research teams.

PMID- 24741693
TI  - 25th anniversary article: Rise to power--OPV-based solar parks.
AB  - A solar park based on polymer solar cells is described and analyzed with respect
      to performance, practicality, installation speed, and energy payback time. It is
      found that a high voltage installation where solar cells are all printed in
      series enables an installation rate in Watts installed per minute that far exceed
      any other PV technology in existence. The energy payback time for the practical
      installation of polymer solar cell foil on a wooden 250 square meter platform in
      its present form is 277 days when operated in Denmark and 180 days when operated
      in southern Spain. The installation and de-installation rate is above 100 m min
      1, which, with the present performance and web width, implies installation of
      >200 W min-1. In comparison, this also exceeds the overall manufacturing speed of
      the polymer solar cell foil with a width of 305 mm which is currently 1 m min-1
      for complete encapsulated and tested foil. It is also significant that
      simultaneous installation and de-installation which enables efficient schemes for
      decommissioning and recycling is possible. It is highlighted where research
      efforts should most rationally be invested in order to make grid electricity from
      OPV a reality (and it is within reach).

PMID- 24741695
TI  - Glucagon-like peptide 1-based therapies and risk of pancreatitis: a self
      controlled case series analysis.
AB  - PURPOSE: Previous studies have suggested a link between glucagon-like peptide 1
      (GLP-1)-based therapies and acute pancreatitis, while other studies have found no
      association. Because differences in diabetes severity may confound this
      relationship, a self-controlled case series (SCCS) analysis has been suggested as
      a means to control for individual-level confounding. METHODS: We evaluated the
      relationship between GLP-1-based therapies and pancreatitis by SCCS method using
      a large observational database. We calculated the incidence density ratio of
      pancreatitis for exposure versus non-exposure to each drug. To examine the
      robustness of our findings, we performed sensitivity analyses by varying risk
      windows, using two pancreatitis definitions and including incident pancreatitis
      or all occurrences. RESULTS: From dispensing data on 1.2 million patients, we
      found 7992 sitagliptin-exposed patients and 3552 exenatide-exposed patients
      between 2004 and 2009. Using an ICD9/CPT-based case definition of pancreatitis,
      we identified 207 sitagliptin and 82 exenatide cases. Augmenting this definition
      with laboratory criteria increased our cohort to 245 sitagliptin and 96 exenatide
      cases. For sitagliptin and exenatide cases, respectively, the mean duration of
      observation was 5.2 and 5.5 years, and the mean duration of drug exposure was 0.7
      and 0.5 years. For all analyses (including different pancreatitis definitions,
      risk periods, and incident or recurrent events), the incidence density ratios for
      development of pancreatitis during exposure versus non-exposure ranged from 0.68
      to 1.46, with all having 95% confidence intervals containing 1. CONCLUSIONS: We
      found no association between the use of GLP-1-based therapies and pancreatitis
      using SCCS analysis in a large observational database.

PMID- 24741696
TI  - Post-licensing safety of fosamprenavir in HIV-infected children in Europe.
AB  - PURPOSE: Fosamprenavir, combined with low-dose ritonavir (FPV/r), is indicated
      for treatment of HIV-infected children aged >= 6 years in Europe. Our purpose was
      to assess the safety of licensed use of FPV/r in HIV-infected children reported
      to six cohorts in the European Pregnancy and Paediatric HIV Cohort Collaboration.
      METHODS: Retrospective analysis of individual patient data for all children aged
      6-18 years taking the licensed dose of FPV up to 31/12/10. Adverse events
      (clinical events and absolute neutrophil counts, total cholesterol and
      triglycerides, and alanine transaminase) were summarised and DAIDS gradings
      characterised severity. RESULTS: Ninety-two HIV-infected children aged 6-18 years
      took the licensed dose, comprising 3% of the total number of children in follow
      up in participating cohorts. Median age at antiretroviral therapy initiation was
      6 years (interquartile range 1-11 years), and median age at start of FPV/r was 15
      years (12-17 years). Estimated median time on an FPV-containing regimen was 52
      months, with a total of 266.9 patient years of exposure overall. Half (54%) were
      on an FPV-containing regimen at last follow-up. Rates of grade 3/4 events were
      generally low for all biochemical toxicity markers, and no serious adverse events
      considered to be causally related to FPV/r were reported. CONCLUSIONS: Results
      suggest that long-term licensed dose FPV-containing regimens appear to be
      generally well tolerated with few reported toxicities in HIV-infected children in
      Europe, although relatively infrequently prescribed. No serious events were
      reported

PMID- 24741697
TI  - Syntactic versus lexical therapy for anomia in acquired aphasia: differential
      effects on narrative and conversation.
AB  - BACKGROUND: Previous studies of therapy for acquired anomia have treated nouns in
      isolation. The effect on nouns in connected speech remains unclear. In a recent
      study in 2012, we used a novel noun syntax therapy and found an increase in the
      number of determiner plus noun constructions in narrative after therapy. AIMS:
      Two aims arose from the previous study: to identify the critical ingredient in
      the noun syntax therapy,specifically whether this is lexical production, or the
      syntactic context; and to extend the analysis of the effects beyond narrative
      into conversation. METHODS & PROCEDURES: We compared the effects of lexical
      therapy with those of noun syntax therapy in one individual with aphasia, in a
      sequential intervention design. We analysed the effects on conversation and on
      narrative. OUTCOMES & RESULTS: There was improved picture naming of treated words
      after both therapies. Lexical therapy had no impact on narrative and
      conversation, whereas noun syntax therapy led to more noun production, primarily
      in the context of determiner plus noun combinations. CONCLUSIONS & IMPLICATIONS:
      The results support the claim that greater impact on narrative and conversation
      can be achieved for some people with aphasia by treating nouns in syntactic
      contexts.

PMID- 24741698
TI  - Reply to Feeley and Machovina: Trophic ecology complements estimates of land use
      change due to food production.

PMID- 24741699
TI  - Reply to Roopnarine: What is an apex predator?

PMID- 24741701
TI  - Image of the month: mysterious universe.

PMID- 24741702
TI  - Diversity of fungi associated with hair roots of ericaceous plants is affected by
      land use.
AB  - Culture-independent molecular studies have provided new insights into the
      diversity of fungi associating with ericaceous plant roots. However, there is
      little understanding of the distribution of these fungi across landscapes, or the
      effects of environmental heterogeneity on ericoid mycorrhizal (ERM) fungal
      diversity and distribution. Terminal-restriction fragment length polymorphism and
      selective sequence analyses of the internal transcribed spacer regions of rDNA
      were used to infer fungal diversity of bait Vaccinium macrocarpon grown in soils
      from nine peatland sites in Ireland, representing three different land uses (bog,
      rough grazing and forest plantation) and the fungal communities of field
      collected Calluna vulgaris for five of these nine sites. A diverse range of
      potential ERM fungi were found, and the sampling approach significantly affected
      the diversity of the fungal community. Despite significant site groupings of the
      fungal communities associated with V. macrocarpon and C. vulgaris, fungal
      communities were significantly dissimilar between sites with different land uses.
      Soil nitrogen content significantly explained 52% of the variation in the V.
      macrocarpon fungal communities. Evidence suggests that environmental
      heterogeneity has a role in shaping ERM fungal community composition at the
      landscape scale.

PMID- 24741694
TI  - 25th anniversary article: Rational design and applications of hydrogels in
      regenerative medicine.
AB  - Hydrogels are hydrophilic polymer-based materials with high water content and
      physical characteristics that resemble the native extracellular matrix. Because
      of their remarkable properties, hydrogel systems are used for a wide range of
      biomedical applications, such as three-dimensional (3D) matrices for tissue
      engineering, drug-delivery vehicles, composite biomaterials, and as injectable
      fillers in minimally invasive surgeries. In addition, the rational design of
      hydrogels with controlled physical and biological properties can be used to
      modulate cellular functionality and tissue morphogenesis. Here, the development
      of advanced hydrogels with tunable physiochemical properties is highlighted, with
      particular emphasis on elastomeric, light-sensitive, composite, and shape-memory
      hydrogels. Emerging technologies developed over the past decade to control
      hydrogel architecture are also discussed and a number of potential applications
      and challenges in the utilization of hydrogels in regenerative medicine are
      reviewed. It is anticipated that the continued development of sophisticated
      hydrogels will result in clinical applications that will improve patient care and
      quality of life.

PMID- 24741703
TI  - Editorial: interdisciplinary with a strong engineering flavor.

PMID- 24741700
TI  - Stability of language performance at 4 and 5 years: measurement and participant
      variability.
AB  - BACKGROUND: Language impairment (LI) in the preschool years is known to vary over
      time. Stability in the diagnosis of LI may be influenced by children's individual
      variability, the measurement error of commonly used assessment instruments and
      the cut-points used to define impairment. AIMS: To investigate the agreement
      between two different age-based versions of a language assessment instrument and
      the stability of the classification of LI using the two measures over a 12-month
      period. METHODS & PROCEDURES: A total of 945 participants completed the Clinical
      Evaluation of Language Fundamentals(CELF-Preschool 2 or 4th Edn) at 4 and 5 years
      of age. Agreement and stability were analysed using Bland-Altman plots,
      correlation and odds ratios. Sensitivity and specificity were calculated for two
      thresholds of the CELF-P2 using the diagnostic category on the child's subsequent
      CELF-4. OUTCOMES & RESULTS: For all CELF scores, mean differences for the cohort
      between 4 and 5 years were within 1.5 scale score units. In contrast, at the
      individual level variability was found across the range of scores and was of a
      greater magnitude than previously reported. Stability in LI classification was
      low, with 36% of 5-year-olds with LI (defined as a standard score below -1.25)
      classified as typical at 4 years, even though odds ratios calculated from
      classifications at the two time points suggested that 4-year-olds with LI had 23
      times greater odds than their typical peers to receive a diagnosis of LI at 5
      years. The CELF-P2 did not demonstrate adequate levels of diagnostic accuracy for
      LI at 5 years: sensitivity of 64% and specificity of 92.9%. CONCLUSIONS:
      Substantial variability across the entire range of possible CELF scores was
      observed in this community cohort between the ages of 4 and 5 years. The
      stability of LI classification was lower than that reported in previous research
      conducted primarily on smaller clinical cohorts. The current study's results
      suggest that the variability observed in developmental language pathways is the
      result of a combination of limitations in measurement instruments, individual
      children's abilities and the arbitrary nature of the boundaries defining LI.

PMID- 24741704
TI  - Bacterial carbon dependence on freshly produced phytoplankton exudates under
      different nutrient availability and grazing pressure conditions in coastal marine
      waters.
AB  - The effects of grazing pressure and inorganic nutrient availability on the direct
      carbon transfer from freshly produced phytoplankton exudates to heterotrophic
      bacteria biomass production were studied in Mediterranean coastal waters. The
      short-term incorporation of 13C (H13CO3) in phytoplankton and bacterial lipid
      biomarkers was measured as well as the total bacterial carbon production (BP),
      viral lysis and the microbial community structure under three experimental
      conditions: (1) High inorganic Nutrient and High Grazing (HN + HG), (2) High
      inorganic Nutrient and Low Grazing (HN + LG) and (3) under natural in situ
      conditions with Low inorganic Nutrient and High Grazing (LN + HG) during spring.
      Under phytoplankton bloom conditions (HN + LG), the bacterial use of freshly
      produced phytoplankton exudates as a source of carbon, estimated from 13C
      enrichment of bacterial lipids, contributed more than half of the total bacterial
      production. However, under conditions of high grazing pressure on phytoplankton
      with or without the addition of inorganic nutrients (HN + HG and LN + HG), the
      13C enrichment of bacterial lipids was low compared with the high total bacterial
      production. BP therefore seems to depend mainly on freshly produced phytoplankton
      exudates during the early phase of phytoplankton bloom period. However, BP seems
      mainly relying on recycled carbon from viral lysis and predators under high
      grazing pressure.

PMID- 24741706
TI  - Notice of retraction.

PMID- 24741705
TI  - [Electronic Cigarettes: "Healthy" smoke and help to abstinence?].

PMID- 24741707
TI  - Opening the genetic toolbox of niche model organisms with high throughput
      techniques: novel proteins in regeneration as a case study.
AB  - Understanding in vivo regeneration of complex structures offers a fascinating
      perspective for translation into medical applications. Unfortunately, mammals in
      general lack large-scale regenerative capacity, whereas planarians, newts or
      Hydra can regenerate complete body parts. Such organisms are, however, poorly
      annotated because of the lack of sequence information. This leads to limited
      access for molecular biological investigations. In the last decade, high
      throughput technologies and new methods enabling the effective generation of
      transgenic animals have rapidly evolved. These developments have allowed the
      extensive use of niche model organisms as part of a trend towards the
      accessibility of a greater panel of model species for scientific research. The
      case study that follows provides an insight into the impact of high throughput
      techniques on the landscape of models of regeneration. The cases presented here
      give evidence of alternative stem cell maintenance pathways, the identification
      of new protein families and new stem cell markers.

PMID- 24741708
TI  - Unravelling the developmental regulatory networks in early animals.

PMID- 24741710
TI  - Axes of differentiation in breast cancer: untangling stemness, lineage identity,
      and the epithelial to mesenchymal transition.
AB  - Differentiation-associated regulatory programs are central in determining tumor
      phenotype, and contribute to heterogeneity between tumors and between individual
      cells within them. The transcriptional programs that control luminal and basal
      lineage identity in the normal mammary epithelium, as well as progenitor and stem
      cell function, are active in breast cancers, and show distinct associations with
      different disease subtypes. Also active in some tumors is the epithelial to
      mesenchymal transition (EMT) program, which endows carcinoma cells with
      mesenchymal as well as stem cell traits. The differentiation state of breast
      cancer cells is thus dictated by the complex combination of regulatory programs,
      and these can dramatically affect tumor growth and metastatic capacity. Breast
      cancer differentiation is often viewed along an axis between a basal-mesenchymal
      stem cell state and a luminal-epithelial-differentiated state. Here we consider
      the links, as well as the distinctions, between the three components of this
      axis: basal versus luminal, mesenchymal versus epithelial, and stem cell versus
      differentiated identity. Analysis on a multidimensional scale, in which each of
      these axes is assessed separately, may offer increased resolution of tumor
      differentiation state. Cancer cells possessing a high degree of stemness would
      display increased capacity to shift between positions on such a multidimensional
      scale, and to acquire intermediate phenotypes on its different axes. Further
      molecular analysis of breast cancer cells with a focus on single-cell profiling,
      and the development of improved tools for dissection of the circuits controlling
      gene activity, are essential for the elucidation of the programs dictating breast
      cancer differentiation state.

PMID- 24741711
TI  - The structure of dynamic GPCR signaling networks.
AB  - G-protein-coupled receptors (GPCRs) stimulate signaling networks that control a
      variety of critical physiological processes. Static information on the map of
      interacting signaling molecules at the basis of many cellular processes exists,
      but little is known about the dynamic operation of these networks. Here we focus
      on two questions. First, Is the network architecture underlying GPCR-activated
      cellular processes unique in comparison with others such as transcriptional
      networks? We discuss how spatially localized GPCR signaling requires uniquely
      organized networks to execute polarized cell responses. Second, What approaches
      overcome challenges in deciphering spatiotemporally dynamic networks that govern
      cell behavior? We focus on recently developed microfluidic and optical approaches
      that allow GPCR signaling pathways to be triggered and perturbed with spatially
      and temporally variant input while simultaneously visualizing molecular and
      cellular responses. When integrated with mathematical modeling, these approaches
      can help identify design principles that govern cell responses to extracellular
      signals. We outline why optical approaches that allow the behavior of a selected
      cell to be orchestrated continually are particularly well suited for probing
      network organization in single cells.

PMID- 24741712
TI  - Comparative morphology of changeable skin papillae in octopus and cuttlefish.
AB  - A major component of cephalopod adaptive camouflage behavior has rarely been
      studied: their ability to change the three-dimensionality of their skin by
      morphing their malleable dermal papillae. Recent work has established that
      simple, conical papillae in cuttlefish (Sepia officinalis) function as muscular
      hydrostats; that is, the muscles that extend a papilla also provide its
      structural support. We used brightfield and scanning electron microscopy to
      investigate and compare the functional morphology of nine types of papillae of
      different shapes, sizes and complexity in six species: S. officinalis small
      dorsal papillae, Octopus vulgaris small dorsal and ventral eye papillae,
      Macrotritopus defilippi dorsal eye papillae, Abdopus aculeatus major mantle
      papillae, O. bimaculoides arm, minor mantle, and dorsal eye papillae, and S.
      apama face ridge papillae. Most papillae have two sets of muscles responsible for
      extension: circular dermal erector muscles arranged in a concentric pattern to
      lift the papilla away from the body surface and horizontal dermal erector muscles
      to pull the papilla's perimeter toward its core and determine shape. A third set
      of muscles, retractors, appears to be responsible for pulling a papilla's apex
      down toward the body surface while stretching out its base. Connective tissue
      infiltrated with mucopolysaccharides assists with structural support. S. apama
      face ridge papillae are different: the contraction of erector muscles
      perpendicular to the ridge causes overlying tissues to buckle. In this case,
      mucopolysaccharide-rich connective tissue provides structural support. These six
      species possess changeable papillae that are diverse in size and shape, yet with
      one exception they share somewhat similar functional morphologies. Future
      research on papilla morphology, biomechanics and neural control in the many
      unexamined species of octopus and cuttlefish may uncover new principles of
      actuation in soft, flexible tissue.

PMID- 24741709
TI  - Using systems biology approaches to understand cardiac inflammation and
      extracellular matrix remodeling in the setting of myocardial infarction.
AB  - Inflammation and extracellular matrix (ECM) remodeling are important components
      regulating the response of the left ventricle to myocardial infarction (MI).
      Significant cellular- and molecular-level contributors can be identified by
      analyzing data acquired through high-throughput genomic and proteomic
      technologies that provide expression levels for thousands of genes and proteins.
      Large-scale data provide both temporal and spatial information that need to be
      analyzed and interpreted using systems biology approaches in order to integrate
      this information into dynamic models that predict and explain mechanisms of
      cardiac healing post-MI. In this review, we summarize the systems biology
      approaches needed to computationally simulate post-MI remodeling, including data
      acquisition, data analysis for biomarker classification and identification, data
      integration to build dynamic models, and data interpretation for biological
      functions. An example for applying a systems biology approach to ECM remodeling
      is presented as a reference illustration.

PMID- 24741713
TI  - Musculoskeletal morphology of the pelvis and pelvic fins in the lungfish
      Protopterus annectens.
AB  - The West African lungfish (Protopterus annectens) performs benthic, pelvic fin
      driven locomotion with gaits common to tetrapods, the sister group of the
      lungfishes. Features of P. annectens movement are similar to those of modern
      tetrapods and include use of the distal region of the pelvic fin as a "foot," use
      of the fin to lift the body above the substrate and rotation of the fin around
      the joint with the pelvis. In contrast to these similarities in movement, the
      pelvic fins of P. annectens are long, slender structures that are superficially
      very different from tetrapod limbs. Here, we describe the musculoskeletal anatomy
      of the pelvis and pelvic fins of P. annectens with dissection, magnetic resonance
      imaging, histology and 3D-reconstruction methods. We found that the pelvis is
      embedded in the hypaxial muscle by a median rostral and two dorsolateral skeletal
      projections. The protractor and retractor muscles at the base of the pelvic fin
      are fan-shaped muscles that cup the femur. The skeletal elements of the fin are
      serially repeating cartilage cylinders. Along the length of the fin, repeating
      truncated cones of muscles, the musculus circumradialis pelvici, are separated by
      connective tissue sheets that connect the skeletal elements to the skin. The
      simplicity of the protractor and retractor muscles at the base of the fin is
      surprising, given the complex rotational movement those muscles generate. In
      contrast, the series of many repeating segmental muscles along the length of the
      fin is consistent with the dexterity of bending of the distal limb. P. annectens
      can provide a window into softtissue anatomy and sarcopterygian fish fin function
      that complements the fossil data from related taxa. This work, combined with
      previous behavioral examination of P. annectens, illustrates that fin
      morphologies that do not appear to be capable of walking can accomplish that
      function, and may inform the interpretation of fossil anatomical evidence.

PMID- 24741714
TI  - In vivo evaluation of cholinesterase activity, oxidative stress markers, cyto-
      and genotoxicity of K048 oxime-a promising antidote against organophosphate
      poisoning.
AB  - K048 is a member of K-oximes, a new oxime class that has recently been confirmed
      effective against poisoning by the nerve agent tabun and several pesticides. The
      toxicity profile of the K048 oxime has not been fully characterized and its
      optimal therapeutic dose has not yet been established. Earlier studies report
      excellent results with K048 in reactivating tabun-phosphorylated AChE and in the
      therapy of tabun-poisoned mice. It possesses a low acute toxicity and exerts an
      acceptable toxicity profile on isolated human peripheral blood lymphocytes in
      vitro. Intraperitoneal administration of K048 in rats resulted in an LD50 of
      238.3 mg/kg. In this in vivo study, we investigated cholinesterase (ChE) activity
      and oxidative stress marker levels (lipid peroxidation and superoxide dismutase
      activity) in the plasma of exposed rats after administering the compound at 25%
      of its LD50. Lymphocyte viability was evaluated using an acridine orange/ethidium
      bromide in situ fluorescent assay. The levels of primary DNA damage in rat white
      blood cells were measured using the alkaline comet assay. The compound applied at
      25% of its LD50 did not significantly affect ChE activity and lipid peroxidation
      and did not cause significant changes in the SOD activity in plasma. The
      cytotoxicity profile of K048 in the tested dose was also acceptable, and it did
      not possess significant DNA-damaging potential. The obtained results are
      promising for further evaluations of the K048 oxime, which should include tests
      on a broader concentration range and longer incubation times.

PMID- 24741743
TI  - Placental lake in high-risk pregnancy.

PMID- 24741744
TI  - Regeneration.

PMID- 24741745
TI  - Clubbing should not be attributed to COPD.

PMID- 24741746
TI  - Metabolic syndrome.

PMID- 24741747
TI  - Response from Dr. Okuda.

PMID- 24741748
TI  - Response from Dr. Niamtu.

PMID- 24741749
TI  - When Anton van Leeuwenhoek looked through his early microscopes in the 1600s, he
      realized that the world was teeming with microbial organisms. Introduction.

PMID- 24741750
TI  - Penn State Hershey Clinical Simulation Center.

PMID- 24741751
TI  - The University of Toronto Surgical Skills Centre: an ACS accredited educational
      institute.

PMID- 24741753
TI  - Physical medicine devices; reclassification of stair-climbing wheelchairs. Final
      order.
AB  - The Food and Drug Administration (FDA) is issuing a final order to reclassify
      stair-climbing wheelchairs, a class III device, into class II (special controls)
      based on new information and subject to premarket notification, and further
      clarify the identification.

PMID- 24741755
TI  - [The concentration of surgical care].

PMID- 24741754
TI  - Black Lung Benefits Act: standards for chest radiographs. Final rule.
AB  - Physicians and adjudicators use chest radiographs (X-rays) as a tool in
      evaluating whether a coal miner suffers from pneumoconiosis (black lung disease).
      Accordingly, the Department's regulations implementing the Black Lung Benefits
      Act allow the submission of radiographs in connection with benefit claims and set
      out quality standards for administering and interpreting film-based chest
      radiographs. This final rule updates the Department's existing film-radiograph
      standards and provides parallel standards for digital radiographs. This rule also
      updates outdated terminology and removes certain obsolete provisions.

PMID- 24741756
TI  - [Not Available].

PMID- 24741757
TI  - [Resection margins-oncology significant parameter R].

PMID- 24741758
TI  - The relationship between the use of fluconazole & the incidence of fluconazole
      resistant Candida species--author's reply.

PMID- 24741759
TI  - Getting hairy for charity. Guys put their razors down in Movember to raise
      awareness of men's health issues.

PMID- 24741760
TI  - 10 minutes with Teddy Fishbein.

PMID- 24741761
TI  - The language of success. Becoming fluent in diversity.

PMID- 24741762
TI  - Influencer marketing. How word-of-mouth marketing can strengthen your
      organization's brand.

PMID- 24741763
TI  - The softer side of health care. How to look less "institutional" online.

PMID- 24741764
TI  - Content is king and connections are queen but patient experiences rule. A digital
      prescription for adopting a customer-obsessed approach to marketing.

PMID- 24741765
TI  - Let the gamification begin.

PMID- 24741766
TI  - Sticker shock!

PMID- 24741767
TI  - The next generation. New models for earned, owned and paid media.

PMID- 24741768
TI  - Oncogenetics saves lifes.

PMID- 24741769
TI  - Alopecia--a challenge for dermatologists.
AB  - Alopecia is a loss of hair in the areas where it normally grows. It has to be
      distinguished from atrichia, the congenital absence of hair due to the absence of
      hair follicles, and hipotrichosis, scarcity or absence of hair in some congenital
      diseases. Alopecia is either scarring, when the skin appears atrophic, scaling,
      and smooth and the hair follicles are absent, or nonscarring, when hair loss is
      not accompanied by the destruction of hair follicles. This paper is a review of
      all types of alopecia and their features in an attempt to make them easier to
      identify and differentiate.

PMID- 24741770
TI  - A review on the cause-effect relationship between oxidative stress and toxic
      proteins in the pathogenesis of neurodegenerative diseases.
AB  - Protein aggregates are the defining pathological feature of human
      neurodegenerative diseases. Studies have revealed that mutant huntingtin,
      polyglutamine-expanded ataxin-1 and ataxin-3 can cause elevated levels of
      reactive oxygen species in neuronal cells. It has also been indicated that the
      normal host prion protein behaves as an antioxidant, while the neurotoxic peptide
      based on the sequence of the scrapie isoform increases hydrogen peroxide toxicity
      in neuronal cultures. Additionally, not only can oxidative stress contribute to
      the aggregation of beta-amyloid and alpha-synuclein, but both beta-amyloid and
      alpha-synuclein can induce oxidative damage. Furthermore, oxidative stressors
      have been shown to play a critical role in neurofibrillary pathology leading to
      tau hyperphosphorylation. In conclusion, the present review supports a cause
      effect relationship between oxidative stress and toxic proteins in the
      pathogenesis of neurodegenerative disorders.

PMID- 24741771
TI  - Multiple sclerosis and pregnancy.
AB  - Multiple sclerosis is one of the main reasons for invalidation of young adults of
      both sexes. The disease is more common in women than in men. The illness begins
      most frequently in patients between the ages of 20 and 40 years, which is also
      the most fertile period for women. MS is an immune-mediated disease with chronic
      evolution marked by exacerbations and remissions that amplify the degree of
      disability. The most common clinical picture is the one with relapse and
      remission whose evolution is greatly improved after immunomodulatory treatment.
      We have revised the literature together with the data from the national multiple
      sclerosis society and the cases that are in the National Programme of Multiple
      Sclerosis, mainly the ones that are assigned to the regional center of Iasi, at
      the Neurology Clinic inside the Clinical Rehabilitation Hospital Iasi. Pregnancy
      is quite frequent in female patients with MS. Certain risks are present during
      pregnancy, birth and breastfeeding and certain protocols must be applied, such as
      interrupting the immunomodulatory treatment before the conception. Child delivery
      must be closely monitored and it must take into consideration the dysfunction
      that the patient has and be adapted to the existing deficits. There are some
      methods that may be used during delivery for female patients with multiple
      sclerosis in order to make this process smooth and reduce the risk of postpartum
      complications. Multiple sclerosis is an invalidating disease, with a high
      prevalence in women. Pregnancy in patients with MS is not such a natural
      phenomenon as in a healthy female and it requires a multidisciplinary team in
      order to ensure the safety of both the mother and the newborn.

PMID- 24741772
TI  - Pruritus in the elderly. Pathophysiological, clinical, laboratory and therapeutic
      approach.
AB  - Generalized pruritus is a common symptom in elderly, patients, with severe impact
      on the quality of life. The diagnosis of senile idiopathic pruritus is made after
      the exclusion of a systemic disease such as chronic renal disease, hepatobilliary
      disease with cholestasis, thyroid dysfunctions, drug-induced hypersensitivity
      reactions, visceral or hematological neoplasia, and primitive dermatological
      distinct conditions. The pathophysiological mechanisms are still unclear. A
      critical role is considered to be played by changes related to skin aging,
      cutaneous nerve supply and other nervous system components. The clinical approach
      requires a thorough assessment of general health status. In primary skin
      conditions, a biopsy and direct immunofluorescence (DIF) are required, while in
      pruritus associated with a systemic disorder, the assessment of hematological,
      biochemical and immunological parameters and imaging are necessary. The treatment
      of a patient with chronic pruritus is often palliative and individualized, with
      emollients, sedating and non-sedating antihistamines, tricyclic antidepressants,
      gabapentinum, and narrow-band UVB phototherapy. Pruritus associated with systemic
      disease may be alleviated by etiologic treatment.

PMID- 24741773
TI  - Anxiety and depression in patients with chronic obstructive pulmonary disease: an
      open agenda for research.
AB  - Depression andnxiety are psychiatric conditions often associated with poor
      survival rate and impaired social functioning in chronic illnesses, like chronic
      obstructive pulmonary disease (COPD). COPD is a major cause of chronic morbidity
      and mortality, being nowadays the fourth leading cause of mortality worldwide and
      the burden of this disease is increasing as the population is ageing and it is
      continuously exposed to risk factors. Common mechanisms for explaining the
      association of anxiety, depression and COPD include cigarette smoke exposure,
      physical inactivity, social isolation, multiple episodes of dyspnea and chronic
      hypoxia. BODE index and MMRC dyspnea score could be associated with anxiety and
      depression in COPD patients and the screening usually implies administration of
      simple questionnaires. Therapeutic options for anxiety include serotonin-reuptake
      inhibitors, which decrease the perception of dyspnea, while newer
      antidepressants, such as venlafaxine, duloxetine and mirtazapine are particularly
      useful in depression, since they do not produce respiratory depression.

PMID- 24741774
TI  - Psoriatic rheumatism. Inflammatory arthropathy.
AB  - Psoriatic rheumatism is an inflammatory arthropathy associated with cutaneous
      psoriasis that occurs mainly in adults aged between 30 and 45 years. In most
      cases, cutaneous phenomena precede rheumatic manifestations. Psoriatic rheumatism
      may begin as a monoarthritis and the diagnosis will be confirmed by the presence
      of psoriatic plaques or by the personal and family history of psoriasis. As a
      chronic proliferative epidermal disease, psoriasis is due to a genetic
      predisposition and it is clinically expressed following the triggering action of
      several factors. The onset is preceded by various events. Psoriasis is two to
      three times more common in patients with arthritis and about 10-20% of psoriasis
      patients show joint damage. AIM: The present study aims to demonstrate the
      clinical and biological efficacy of biotechnology-derived biologic drugs, acting
      as TNFalpha antagonists and used as backup therapy, at the same time bringing new
      hope for broadening and improving therapy in psoriatic arthropathy. MATERIAL AND
      METHODS: The study included a total of 21 patients (13 men, 8 women) admitted in
      the interval 2011-2012 to the I-st Rheumatology Clinic of the Iasi Rehabilitation
      Hospital. The patients were older than 20 years and had one or more peripheral
      arthritis conditions, skin and nail lesions. RESULTS AND DISCUSSION: Based on the
      results, it is recommended that infliximab to be administered in patients who
      meet CASPAR ((Classification Criteria for Psoriatic Arthritis) diagnostic
      criteria, have the disease in aggressive stage, and do not respond to treatment
      with methotrexate (MTX) or other disease-modifying antirheumatic drugs--DMARDs
      (leflunomide, sulfasalazine) administered for 12 weeks. CONCLUSIONS: Infliximab
      is effective in counteracting the potentially harmful elements. It reduces the
      number of tender and swollen joints, improves the functional capacity and the
      quality of life, and slows down the radiologic progression. Infliximab is well
      tolerated, effective, with an optimum safety profile during short-term
      administration in patients with active forms of psoriatic arthropathy.

PMID- 24741775
TI  - Parkinson's disease and carotid intima-media thickness.
AB  - Reports about the impact of cerebrovascular disease (CVD) on clinical status in
      Parkinson's disease (PD) are rather controversial. There have been a few studies
      and inconsistent results regarding the coincidence of Parkinson's disease (PD)
      and atherosclerotic diseases, such as cerebrovascular disease. Carotid intima
      media thickness (IMT) is a known marker for subclinical atherosclerosis. AIM:
      This study was done to investigate the carotid IMT between PD patients and
      controls. MATERIAL AND METHODS: A total of 54 PD patients and 50 controls were
      examined. The duration of Parkinson's disease, the severity of Parkinson's
      disease (the Hoehn-Yahr stage) and carotid IMT were examined. RESULTS: The mean
      Hoehn and Yahr stage was 2.78 (range 2-4). Duration of disease had a mean of 7.59
      +/- 0.85 years. The left CCA mean IMT was 0.900 +/- 0.147 in Parkinson group and
      0.828 +/- 0.118 in control group (p = 0.007). The right CCA mean IMT was 0.891 +/
      0.176 mm in the Parkinson group and 0.860 +/- 0.164 in control group (p =
      0.360). No relationship between the Hoehn and Yahr stages or the duration of PD
      with the IMT were found by the Pearson's correlation test. CONCLUSIONS: The
      carotid IMT was higher in PD patients than in controls.

PMID- 24741776
TI  - Predictive value of a positive exercise stress testing and correlations with
      cardiovascular risk factors.
AB  - Electrocardiogram exercise stress test (EST) is a widespread technique in
      assessment of coronary artery disease, stratifying cardiovascular risk and
      prognosis. AIM: Evaluation of the impact of cardiovascular risk factors upon the
      results of EST. METHODS: The 2-year retrospective study included 294 patients
      referred to an EST. All patients were assessed according to: presence of typical
      angina chest pain at admission, medical history of angina or myocardial
      infarction, resting electrocardiogram, global ejection fraction at
      echocardiographic exam and traditional cardiovascular risk factors. We compared
      the results between two groups: positive and negative EST. RESULTS: The patients
      were age- and sex-matched. 160 patients (54.42%) had a positive EST. Positive EST
      was associated with typical angina chest pain at admission (88.12% vs. 76.11%, p
      = 0.008), coronary artery disease history (61.87% vs. 41.04%, p = 0.0003),
      resting ECG abnormalities (49.37% vs. 36.56%, p = 0.026), arterial hypertension
      (85.62% vs. 74.62%, p = 0.019). Ejection fraction was higher in the negative EST
      group (63.34 +/- 8.57% vs. 61.18 +/- 11.34%, p = 0.035). Type 2 diabetes
      mellitus, smoking, obesity, dyslipidemia and inflammatory syndrome did not
      significantly influence the results of the EST. CONCLUSIONS: Typical angina,
      medical history of coronary artery disease, arterial hypertension, and reduced
      ejection fraction are strong predictors for a positive exercise stress test.

PMID- 24741777
TI  - Thyroid dysfunction and ischemic heart disease--clinical correlations,
      progressive implications and impact on the prognosis.
AB  - Thyroid dysfunctions are associated with systolic and diastolic heart
      dysfunction, hypertension, rhythm disorders, etc. Clinically significant
      hyperthyroidism and hypothyroidism may have an impact on the patients with
      ischemic heart disease. OBJECTIVES: Investigation of the risk of developing
      ischemic heart disease, of the evolution and prognosis in relation to the entire
      spectrum of thyroid dysfunctions. MATERIALS AND METHODS: All participants
      included in the study were selected from among subjects with heart disorders who
      were controlled with concern to the thyroid hormonal condition and who hadn't
      been treated previously for thyroid functional disorders. Based on these criteria
      we defined a study group made out of 791 subjects, divided into five lots based
      on the level of thyroid hormones. Once the group was formed, we conducted
      evaluations of the cardiovascular and thyroid status at 6 and 12 months,
      respectively. RESULTS: In the witness lot, during monitoring 49% of the patients
      showed an ischemic heart disease. The main risk factors were: heart frequency of
      over 80 beats/min (RR = 1.83), age over 60 (RR = 1.47), female sex (RR = 1.21)
      and values of triglycerides over 160 mg/dl (RR = 1.23). In the group of patients
      with overt clinic hyperthyroidism, during monitoring 46.1% showed ischemic heart
      disease. The main risk factors were: heart frequency over 80 beats/min (RR =
      2.41), age over 60 (RR = 1.67), high level of LDL-cholesterol (RR = 1.53) and
      female sex (RR = 1.31). Among the patients with overt clinical hyperthyroidism,
      during monitoring 53.3% showed ischemic heart disease. The main risk factors
      identified were: heart frequency over 80 beats/min (RR = 2.01), age over 60 (RR =
      1.42), high levels of triglycerides (RR = 1.42) and LDL-cholesterol (RR = 1.32),
      as well as the presence of hypertension in the health records (RR = 1.31).
      CONCLUSIONS: Thyroid dysfunction is a common clinical condition with a key role
      in the regulation of the cardiovascular system and may contribute to the
      evolution of the ischemic heart disease and which should be taken into
      consideration when patients with heart disease are treated. In this light,
      thyroid function needs to be evaluated for all patients with a risk for ischemic
      heart disease.

PMID- 24741778
TI  - Clinical features and evolution of organ dysfunctions in sepsis.
AB  - In sepsis, the systemic inflammatory response is adapted to the etiologic agent
      and the increase in the level of mediators is associated with organ dysfunction.
      Currently, a rapid assessment of patient ability to develop an adequate immune
      response is not possible, the response mechanisms being similar in the context of
      different etiological agents. AIM: To find statistical arguments for the
      evolution of laboratory parameters in sepsis patients. MATERIAL AND METHODS: This
      retrospective study included 90 patients diagnosed with sepsis. The clinical,
      etiological, and laboratory data, and Carmeli and APACHE II prognostic scores
      were analyzed. The data were processed using SPSS version 16.0. RESULTS: The
      causative agents was identified in 16 cases; organ involvement and systemic
      response varied, and no statistical correlations were found between the
      inflammatory syndrome parameters and Carmeli or APACHE II prognostic scores or
      identification of the causative agent. CONCLUSIONS: Statistical correlations were
      found between maximum blood glucose levels and the presence of organ dysfunction
      in the studied sepsis patients. No correlations were found between sepsis
      severity and the presence of anemia or thrombocytopenia, or between fever
      syndrome and inflammatory syndrome.

PMID- 24741779
TI  - Orthostatic intolerance--an expression of autonomic disfunction in Parkinson's
      disease.
AB  - Orthostatic intolerance syndrome is an important issue, having multiple
      etiologies and being the result of an inadequate response to changing in body
      position, namely the transition from supine to standing, a process that causes a
      series of responses regulated by the autonomic nervous system. AIM: The aim of
      this study was to create a profile of patients with Parkinson's disease and
      orthostatic hypotension, a form of orthostatic intolerance, identifying the risk
      factors for this condition. MATERIAL AND METHODS: We conducted a study on 41
      patients with Parkinson's disease selected from 200 consecutive patients with
      orthostatic hypotension, hospitalized in Cardiology Clinic of Colentina Clinic
      Hospital which met the diagnosis criteria for orthostatic hypotension. In order
      to meet the inclusion criteria, all patients were evaluated according to a preset
      protocol: medical history, clinical and paraclinical examination, including neuro
      psychiatric assessment and the orthostatic tolerance test. RESULTS AND
      DISCUSSION: The decline in standing blood pressure was related to the presence of
      hypotensive neurological drugs, especially Levodopa, in chronic treatment, but it
      was not influenced by age or cardiovascular co morbidities. There is an
      improvement in blood pressure both in supine and upright position at discharge
      when compared to admission values. CONCLUSION: The degree of decrease in the
      standing blood pressure values was correlated with the presence of potentially
      hypotensive neurological drugs, particularly Levodopa treatment, with a favorable
      effect of administration of non-pharmacological treatment and changes made in
      chronic neurological treatment.

PMID- 24741780
TI  - Infectious endocarditis with five localisations--case reports.
AB  - Infectious endocarditis is defined as an infection of the endocardial surface
      area of the heart which can include one or more cardiac valves, mural endocardium
      or a septal defect. We present the case of a patient, aged 8, hospitalized in
      Hemato-Oncology Department with pontine glioma, who was also diagnosed with
      infectious endocarditis in five locations.

PMID- 24741781
TI  - Massive pericardial effusion associated with hypothyroidism.
AB  - The diagnosis of hypothyroidism is difficult because hypothyroidism in adults and
      especially the elderly, classic, has an insidious onset with a range of
      nonspecific symptoms which may delay diagnosis for months or even years. Old age
      seems to represent trigger factor for autoimmune diseases, including
      hypothyroidism. Clinical features in hypothyroidism, such as weight gain,
      fatigue, cold intolerance, constipation, dry skin, edema and muscle weakness, and
      decreased osteo-tendinous reflexes are usually subtle and can be overlooked.
      Thyroid dysfunction may be associated with a negative impact on the
      cardiovascular system. Pericardial, pleural and peritoneal effusions are common
      findings in hypothyroidism. This case report represents a typical primary
      hypothyroidism (autoimmune) and shows the clinical features of this disease.
      Basically we talked about a severe myxedema with the involvement of internal
      organs in an elderly woman and the euthyroidism restoration, under thyroid
      replacement therapy, was correlated with the clinical improvement and
      cardiovascular and neurological status, with radiographic remission and
      regression to extinction of pericardial effusion at repeated echocardiographic
      evaluations.

PMID- 24741782
TI  - Pact with the devil: alemtuzumab therapy, immune suppression and infectious
      complications in chronic lymphocytic leukemia.
AB  - Infectious complications are an important cause of hospitalization in patients
      diagnosed with chronic lymphocytic leukemia. The pathogenesis of infection is
      complex, involving both disease-induced and treatment-related immune depression.
      During the last decade, the management of chronic lymphocytic leukemia (CLL) has
      been redefined by the approval of monoclonal antibody-based treatment, which
      resulted in improved therapeutic responses. Nonetheless, the profound lymphopenia
      induced by monoclonal agents was accompanied by increased incidence of infections
      caused by a new spectrum of opportunistic microorganisms. We report the case of a
      patient with hypercellular CLL who received Alemtuzumab as first line therapy and
      obtained a satisfactory therapeutic response, but developed subsequent atypical
      infectious complications.

PMID- 24741783
TI  - A case of severe hypoalbuminemia associated with chronic congestive heart
      failure: the role of the tricuspid regurgitation.
AB  - Hypoalbuminemia is considered an independent predictor of mortality, especially
      in elderly patients. It is common in patients with congestive heart failure, when
      is due to several mechanisms: increased volume of distribution, significant
      stasis in the mesenteric circulation and altered protein metabolism in the liver.
      These alterations are even more pregnant when tricuspid regurgitation is
      associated or aggravated by different risk factors (recent infections, anemia,
      hyperthyroidism). We present the case of an elderly patient with severe
      hypoproteinemia and important hypoalbuminemia associated with congestive heart
      failure and aggravation of tricuspid regurgitation. The differential diagnosis
      concluded that hypoalbuminemia was influenced by tricuspid regurgitation as it
      enhanced liver dysfunction and enteral protein absorption due to increased stasis
      in mesenteric system. On the other hand, hypoalbuminemia contributed to the
      progression of heart failure by favoring myocardial edema, volume overload, and
      diuretic resistance. This is why correct management of this situation should
      include removal of subclinical excess of fluid and renutrition. A
      multidisciplinary approach is needed in order to achieve a good control of the
      symptoms and a significant improvement of quality of life.

PMID- 24741784
TI  - Leishmaniasis--an unusual cause of splenomegaly in Romania.
AB  - Leishmaniasis is a parasitic infection caused by protozoans classified as
      Leishmania species. Romania is not considered an endemic country and there are
      only few reports of sporadic cases in the last 100 years. However, studies
      suggest that the disease is spreading north. We present the case of a 44 year old
      female that presented with asthenia, perspirations, vertigo, weight loss and
      menometrorhagias in small to medium quantity. Clinical exam revealed the presence
      of splenomegaly and her blood tests indicated she had pancitopenia; differential
      diagnosis included myeloproliferative or lymphoproliferative disorders,
      infections that evolve with spleen enlargement, autoimmune-related splenomegaly
      and hepatic--all tests were negative. She refused the bone marrow aspiration.
      Three months later, her condition worsened and the menometrorragias became more
      severe. Bone marrow aspiration revealed the presence of numerous intra and
      extracellular Leishmania spp. amastigotes. A detailed anamnesis showed that she
      had worked for six months in Italy as a care-giver nine months ago. She was
      transferred to Bucharest where she received optimal treatment. However, due to
      the continuous bleeding, the evolution was unfavourable. This is an alarm sign
      for physicians that should take into account the fact that, due to population
      migration and global warming, tropical infectious diseases are becoming more and
      more common. The signs and symptoms, as well as the treatment in leishmaniasis
      are reviewed, as well as a brief history of leishmaniasis in Romania.

PMID- 24741785
TI  - Three synchronous primary pelvic cancers--a case report.
AB  - The occurrence of synchronous primary gynaecologic malignancies is a relatively
      common event. However, the occurrence of three different pelvic cancers is very
      rare. In this report, we describe the clinical, surgical and pathological
      findings of a patient with synchronous primary malignancies of the fallopian
      tube, endometrium and sigmoid colon. To our knowledge, it is the first case
      described in the literature with such an association of primary synchronous
      cancers.

PMID- 24741786
TI  - Bipolar disorder, not so rare diagnosis: subtypes of different degrees of
      severity, diagnosis, therapy.
AB  - Bipolar disorder is manifesting as a mood disorder, typically showing episodes of
      mania, alternating with depressive episodes. The subtypes are including bipolar I
      disorder (one or several manic episodes) and bipolar II disorder (hypomanic
      episodes and one or several major depressive episodes). Nevertheless, sub
      threshold diagnosis criteria may include another 5.1, up to 6.4% of the
      population as having a bipolar spectrum disorder diagnosis. Anyone who received
      the diagnosis is not considered cured afterwards (just in remission). Diagnosis
      is considering the symptoms of mania, hypomania and depression. Therapy is based
      on lithium, anticonvulsants, for the manic symptoms, lamotrigine for the
      depressive episodes and antipsychotics. Under medication, most of the affected
      subjects are living a normal life; to a certain degree, medication may also
      prevent the relapses.

PMID- 24741787
TI  - Effects of some dopamine antagonists on spatial memory performance in rats-
      experimental research.
AB  - Dopamine is a neurotransmitter with an important role in forming long-lasting
      memories for some time, especially in episodic memory. Literature data show that
      dopamine receptor stimulation may be detrimental to spatial working memory
      functions in lab animals. (R)-(+)-7-Chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5
      tetrahydro-1H-3-benzazepine hydrochloride derivative--SCH-23390 is a synthetic
      compound that acts as a selective, high-affinity antagonist of D1 receptors.
      Experimental studies suggest that SCH 23390 may prevent the spatial working
      memory disturbances induced by the active substances of marijuana. Melperone is
      an atypic antipsychotic drug presenting also dopaminergic D2 and 5-HT2A receptor
      antagonistic activity. This neuroleptic agent is used in the treatment of some
      types of schizophrenia. AIM: Experimental research on the effects of two dopamine
      receptor antagonists on spatial memory performance in rats. MATERIAL AND METHODS:
      The experiment was carried out in white Wistar rats (200-250g), divided into 3
      groups of 7 animals each, treated intraperitoneally with the same volume of
      solution for 14 days, as follows: Group I (Control): saline solution 0.1 ml/10g
      kbw; Group II (coded SCH): SCH-23390 0.3 mg/kbw; Group III (coded MLP): melperone
      2 mg/kbw. The dopaminergic agent spatial memory performance was assessed by
      recording spontaneous alternation behavior in a single session in Y-maze. Each
      animal was placed at the end of one arm and allowed to move freely through the
      maze during an 8 min session. Alternation was defined as a consecutive entry in
      three different arms. The alternation percentage was computed with the following
      formula: number of alternations divided by total number of arm visits minus 2.
      Data were presented as +/- standard deviation and significance was tested by SPSS
      Statistics for Windows version 13.0 and ANOVA method. P-values less than 0.05
      were considered statistically significant compared to those in the control group.
      Experimental researches were carried out in compliance with the regulations of
      our University Committee for Research and Ethical Issues. RESULTS: SCH-23390 (0.3
      mg/kbw) and melperone (2 mg/kbw) intraperitoneal injection for 14 days determined
      a statistically significant (p < 0.05 and p < 0.01, respectively) increase in
      spontaneous alternation rate (compared to controls in Y-maze test). CONCLUSIONS:
      Our research revealed that the 14 consecutive days administration of these two
      dopamine receptor antagonists was associated with the improvement of short-term
      memory in rats, more intense for SCH-23390 compound.

PMID- 24741788
TI  - The effects of two polymeric matrices for indomethacin in cutaneous nociceptive
      reactivity in mice.
AB  - AIM: This paper is focused on the investigation the effects of two polymeric
      matrices for indomethacin in cutaneous pain models in mice. There were used two
      different co-polymers polyhydroxyethyl methacrylate and undecan, polymerization
      reactions being conducted under nitrogen, at 80 degrees C. MATERIAL AND METHODS:
      The experiments were carried out on white Swiss mice (20-25 g), divided into 6
      groups of 7 animals each, treated orally. Biocompatibility properties of
      indomethacin-loaded copolymeric matrices ware evaluated by assessing the effects
      on the blood parameters, the serum biochemical tests of animals treated. The
      nociceptive somatic testing was performed using hot plate assay and tail
      immersion test. The latency (second) response to paw, respectively tail thermal
      noxious stimulation, was measured before the experiment and 15, 30, 60, 90, 120
      minutes, 4, 6, 8, 10, 12 hours after the substances administration. RESULTS:
      Laboratory analysis did not show significant differences of blood parameters,
      serum biochemical tests between control mice group (IND) and groups treated with
      1 M, 1 IND, 3 M, 3 IND. In our experimental conditions IND determined a
      significant increasing of the latency period response, in hot plate and also in
      tail immersion tests. Using two different co-polymers for indomethacin
      incorporation we obtained an increasing of the latency time pain reaction in hot
      plate assay, respectively in tail immersion test, statistically significant (*p <
      0.05) compared with the simple copolymers administration. CONCLUSIONS: We
      demonstrated that indomethacin co-polymeric matrices 1 IND and 3 IND determined
      similar immune responses with indomethacin and simple co-polymers after oral
      administration in mice, indicative of good in vivo biocompatibility. Oral
      administration of both 1 IND and 3 IND resulted in prolonged antinociceptive
      effects in hot plate assay and also in tail immersion test in mice.

PMID- 24741789
TI  - Rad51 overexpression and resistance to genotoxic agents. A study in the fission
      yeast Schizosaccharomyces pombe.
AB  - BACKGROUND: Many cancer cell lines have been found to overexpress the recombinase
      Rad51. The overexpression is associated with increased invasive potential and
      resistance to DNA-damaging therapeutic agents. This has been attributed to an
      increased capacity of cells overexpressing Rad51 to repair DNA lesions or to a
      genetic stabilization of the genome. AIM: As the explanations are somewhat
      controversial, we attempted to reproduce overexpression in the unicellular
      eukaryote Schizosaccharomyces pombe to have a simpler tool to study the problem
      of Rad51 overexpression and its induced resistance to DNA-damaging agents.
      METHODS: We used the nmt1 promoter inserted upstream of rad51 gene to induce its
      overexpression and studied the phenotype of the transformed strain, especially
      its sensitivity to camptothecin and hydroxyurea. RESULTS: We found that
      overexpression induced sensitivity to the two drugs even when it was associated
      with the deletion of a recombination mediator rad22/rad52 gene. However, when
      overexpression was associated with the deletion of the helicase-encoding fbh1
      gene, the sensitivity to camptothecin was diminished.

PMID- 24741790
TI  - Clinical, epidemiological and prophylactic aspects of dyspepsia.
AB  - Dyspepsia or indigestion is a term that refers to a multitude of symptoms and
      disorders of the digestive system which cause suffering in many patients.
      Dyspepsia means pain or discomfort that is centrally localized in the upper
      abdomen. The following categories of symptoms may also be present: pain localized
      in the right or left hypochondrium, dysphagia, upper gastrointestinal bleeding,
      acute abdomen, symptoms of reflux, transit disorders. On the other hand, the term
      "discomfort" was defined in order to designate a condition characterized by or
      associated with early satiety, upper abdominal bloating, nausea, epigastric
      fullness. As dyspeptic syndrome is often caused by excessive food intake or by
      consumption of certain nutrients, the disease may have a severe prognosis. Hearty
      meals, the nature of foods, the preparation of meals, possible special conditions
      of eating may often contribute to dyspepsia.

PMID- 24741791
TI  - Retrospective study on the etiological spectrum and antibiotic resistance in
      infections associated with osteosynthesis materials.
AB  - AIM: To determine the prevalence of infections according to their etiologic
      spectrum and antibiotic sensitivity in patients with or without implants and
      endoprostheses. MATERIAL AND METHODS: This retrospective study was conducted
      based on a customized study protocol on 773 cases admitted to the Clinic of
      Orthopedics - Traumatology of the Iasi "Sf. Spiridon" Emergency Hospital in the
      interval January 1, 2003 - December 31, 2011 for postoperative infectious
      complication. RESULTS: S. aureus was more frequently found in the patients
      without implant (58.2%) and in those with subcutaneous implant (45.5%); the
      lowest frequency was noticed in the patients with endoprosthesis (27.1%), the
      frequency distributions showing marked statistically significant differences (p =
      0.001). P. aeruginosa was more frequently detected in the patient group with
      endoprosthesis (30.2%), while in the other groups it was found in approximately
      7% (p = 0.001). The presence of Acinetobacter spp. was significantly higher in
      patients with deep implant (12.9%), with the lowest frequency noticed in the
      patients without implant (4.5%) (p = 0.029). Of the total isolated and identified
      types, 59.6% were non-multidrug-resistant (non-MDR), the remaining 40.4% being
      MDR types. CONCLUSIONS: S. aureus was the most frequent etiological agent in
      patients with or without cutaneous implant (45.5 and 58.2%, respectively), and P.
      aeruginosa (30.2%) in the endoprosthesized patients. Implementation of a
      preoperative screening protocol for the identification of healthy S. aureus
      carriers (Methicillin-sensitive S. aureus - MSSA/Methicillin-resistant S. aureus 
      MRSA) and subsequent decolonization would be an efficient way of reducing the
      incidence of infections caused by this bacterium.

PMID- 24741792
TI  - Smoking generated PM 2.5 exposure among Transylvanian students.
AB  - A WHO project initiated in 2004, tries to identify and reduce the number of
      smoking third year university students attending medical training in Medicine,
      Dentistry, Pharmaceutical sciences as these participants can become role models
      that patients can look up to. AIM: We proposed to make a general view regarding
      smoking and exposure to smoke within our medical University, in contrast with the
      existing legislation regarding smoking within public institutions of the
      Universities. Along with the investigations held at our university we extended
      these to other tree, non medical universities. MATERIALS AND METHODS: Using an
      TSI Pack Aerosol Monitor unit to measure the total PM 2.5 we determined the air
      quality in several target locations of our University in holiday season and
      during full didactical periods. The average values were later compared and
      assessed in a series of statistical tests. RESULTS: Analyzing the holiday period
      our university head the most polluted air showing the P.M. 2.5 of 0.016 mg/m3. In
      the following there were analyzed the recordings from the didactic period where
      the registered values were significantly higher (p < 0.0001) in comparison with
      the readings from the holiday season. From several points within the universities
      there were reading 7 times higher than in the holiday season. CONCLUSIONS: The
      results show two evident conclusion, that there is smoking within the buildings
      of the universities and within our university the non-smoking students are
      totally exposed to exhaled cigarette smoke.

PMID- 24741793
TI  - Self-medication with antimicrobial drugs among university students in a Northeast
      region of Romania.
AB  - Self-medication with antimicrobial drugs is an important problem in the world and
      may lead to serious consequences for healthcare systems. OBJECTIVE: To evaluate
      the prevalence and patterns of self-medication with antimicrobial drugs among
      university students in a Northeast region of Romania. MATERIAL AND METHODS: A
      cross-sectional questionnaire-based study was conducted to collect data from
      medical and non-medical students who lived in residence halls. Data were analyzed
      using descriptive statistics and the chi-square test, when applicable. RESULTS:
      Out of the 320 questionnaires distributed, a total of 281 students completed and
      returned the questionnaires. Among these, 115 (41%) respondents admitted to have
      used at least one antibiotic in the six months prior to the survey, 44% of whom
      did not seek medical advice (irrational self-medication). The most common
      antimicrobial drugs used for self-medication were amoxicillin (37%), amoxicillin
      clavulanate (33%), ciprofloxacin and penicillin (14%) and the most frequently
      reported reasons for self-medication were respiratory and oral infections (31%),
      common cold (25%), and genitourinary infections (20%). Some students mentioned
      the use of more than one antimicrobial drug, for more than one disease.
      CONCLUSIONS: self-medication with antimicrobial drugs is a relatively common
      practice among students in Romania. This suggests the need for interventions to
      prevent the irrational use of antimicrobial drugs, such as the implementation of
      national programs for public education regarding the risks and consequences for
      the health of irrational use of antimicrobials.

PMID- 24741794
TI  - Clostridium difficile epidemic outbreak in an oncology unit.
AB  - AIMS: Contributions to the knowledge of some peculiarities of C. difficile
      involvement in human pathology, nosocomial infections (NI) included. MATERIAL AND
      METHODS: This clinico-epidemiological and laboratory study included 14 patients
      admitted to the Medical Clinic of the Iasi Regional Cancer Institute with the
      diagnosis of C. difficile NI based on detection of toxins A and B in stool
      samples. The data were assessed and interpreted using an algorithm which revealed
      the peculiarities of C. difficile NI outbreak occurrence and evolution. RESULTS:
      Of the 14 cases included in the study, 5 (35.8 %) had community-onset infections
      and 9 (64.3%) oncology unit-onset infections. The average hospital stay was 22
      days. Immunocompromised condition and the use of antibiotics in the
      ciprofloxacin, colistin and cefotaxime group for 4 - 10 days were the main risk
      factors. CONCLUSIONS: This epidemic C. difficile NI outbreak which affected
      immunocompromised patients with high susceptibility to infection, common finding
      in oncology care was brought under control by active preventive measures
      associated with concomitant antimicrobial therapy effective in C. difficile
      infections.

PMID- 24741795
TI  - Palliative care--integration model into oncological assistance for the patients
      of Regional Institute of Oncology Iasi.
AB  - AIM: This paper aims to present a retrospective analysis of activity from
      Palliative Care Compartment of Regional Institute of Oncology Iasi during 12
      months of activity and to propose a model of integration of the palliative care
      in oncology. MATERIALS AND METHODS: Data were collected from 415 patients
      hospitalized to the Palliative Care Compartment using the computerized database,
      records and books of existing appointments. RESULTS: Data analysis reveals that
      170 cases (40%) were aged higher or equal to 70 years and a number of 142
      patients (34%) were aged between 60-69 years. Results regarding the provenience
      of the patients shows that most of them are from urban areas. Gastrointestinal
      neoplasms were present at about one-third of the patients--133 cases (32%) and 95
      (71%) of these cases had metastases. Most patients--114 cases (27%) required
      hospitalization for a period between 8 and 14 days. Palliative care has
      interdisciplinary relations with other specialties. In 2013 from other
      specialties were transferred to palliative care a number of 156 patients, most of
      them (87 cases) from Oncology Department. CONCLUSIONS: Integrating palliative
      care in oncology would increase the quality of life of patients, would relieve
      the other sections or hospitals by patients who need palliative care, would
      decrease hospitalization costs and would avoid performing aggressive maneuvers at
      the end of life.

PMID- 24741796
TI  - The implications of hazardous waste neutralization on employees health: a case
      study.
AB  - Chronic obstructive pulmonary disease is a lung disorder characterized by chronic
      inflammation of the respiratory tract after exposure to pollutants, causing the
      obstruction of small respiratory tracts and the destruction of lung parenchyma.
      These changes ultimately lead to a limitation of air flux. We investigate the
      association between professional exposure and the risk of developing chronic
      obstructive pulmonary disease. This study presents the case of a non-smoker
      patient, aged 61, a mechanic locksmith by profession at a hospital in Mures
      County. He has been working with neutralization of medical waste for 13 years
      with exposure to pneumotropic and biological contaminants and to the overuse of
      osteoarticular apparatus, recently having been diagnosed with COPD after exposure
      to mixed powders and hospitalized at the occupational health clinic. Interruption
      of occupational exposure and establishment of treatment with topical
      corticotherapy has shown a significant improvement. Measurements of inhalable
      powder content in the work environment revealed that they exceed the allowed
      limit in case of neutralization of medical waste and there is an association
      between occupational exposure and increased risk of chronic obstructive pulmonary
      disease. Preventive methods should aim to reduce exposure at workplace.

PMID- 24741797
TI  - Subacute fungal endocarditis due to Acremonium spp: a case study and review of
      the literature.
AB  - A 52 years old patient is hospitalized in June 2007 in the Cardiology Clinic of
      Cardiovascular Diseases Medical Institute in Iasi with suspected subacute
      infectious endocarditis. Echocardiography shows mobile vegetation on the
      pulmonary valve. Acremonium spp is isolated from blood cultures after 2 weeks of
      incubation. The patient was treated with fluconazole, but died after 3 months due
      to renal failure.

PMID- 24741798
TI  - Dental esthetics--instrument for recreating a new facial esthetic to the elderly
      patient.
AB  - AIMS: The major objective of this paper consists in underlining the wide range of
      possibilities in assessing the elderly patient; it relies on clinical examination
      in order to exclusively improve the patient's physiognomic aspect. MATERIALS AND
      METHODS: In this context it has been organized a study which included 64 elderly
      patients aged between 60 and 90 years of age (median age 75), which presented
      themselves at the Clinical Service of Dental Semiology and Gerontostomatology
      between 2011-2012; they requested the restoration of the functions affected by
      odontal coronary lesions, periodontal disorders or edentations more or less
      expanded, malocclusions, malrelations of the mandible to the skull and
      unsuccessful or deteriorated dental or prosthetic treatments. RESULTS: The
      restoration of dental arches has been performed relying on common sense and power
      of discernment, respecting both facial features and expression by redimensioning
      the lower part of the face, repositioning the mandible and using gnatoprosthetic
      devices. CONCLUSIONS: Solving the problems elderly patients confront themselves
      with and the success of the treatment has been possible only after a correct
      assessment of the involutive phenomena that influence the oral cavity, after
      understanding the local and general factors that predispose to oral disorders as
      well as the differences between various techniques and materials.

PMID- 24741799
TI  - Young patients' perception on different surgical management of the disto-occlusal
      gingival operculum in second mandibular molars.
AB  - AIM: This baseline study aims to find out the young patients' perception on
      different surgical management of the disto-oclusal gingival operculum in second
      mandibular molars: the conventional technique and the laser assisted one.
      MATERIAL AND METHODS: The current study included a batch of 20 patients who
      needed surgical bilateral removal of the disto-oclusal operculum in second
      mandibular molars order for them to receive conservative treatment. Each patient
      benefited of two different surgical techniques (laser assisted and conventional).
      Patients' perception towards these procedures was evaluated with a simple
      questionnaire. RESULTS: The questionnaires were evaluated by a specialized team
      and the results were illustrated in the specific charts. On one hand the
      conventional technique wasn't perceived as very comfortable and on the other hand
      the laser assisted technique was very well perceived by the patients.
      CONCLUSIONS: The overall perception of young patients towards laser assisted
      periodontal surgery was very high and this is a means of reducing operating time
      and anxiety caused by the surgery itself.

PMID- 24741800
TI  - Study of dental and skeletal disorders in mono- and dizygotic twins.
AB  - The aim of this study was to analyze and to compare the dental and skeletal
      morphology of mono- and dizygotic twins (MZ and BZ). MATERIAL AND METHODS: 10
      sets of monozygotic (mean age: 18.5 years) and 10 sets of dizygotic (mean age:
      19.7 years) twins were examined, cast analysis, ortopantomography and lateral
      cephalometric films were analyzed. RESULTS: The upper frontal teeth dimension and
      shape is the same in 99.69% of MZ and 93.91% of the DZ twins. In MZ twins we
      found different values for transversal arch width and upper intercanine distance.
      The dental malpositions were different in the DZ sets, especially in tranversal
      and sagital plan. The same differences were seen in the arch forms. The skeletal
      pattern was also different between the components of DZ twins. The cephalometric
      values showed slight differences of the interincisal angle both in MZ and DZ
      twins. CONCLUSIONS: Genetically influenced patterns can be explained by the
      results of our study.

PMID- 24741801
TI  - Examination of Bolton Index comparing the traditional method with a 2-dimensional
      digital measurement method.
AB  - Index is one of the most important analyses in orthodontic treatment planning. It
      shows if there is a correct proportion in size between the maxillary and
      mandibular teeth. In this study we compared the digital and traditional method.
      METHODS: 35 dental casts were measured using a Vernier caliper. The mean value
      was compared with the measurements from the scanned images of the dental casts.
      RESULTS: The results showed that the digital method provided similar results with
      those of the traditional one with a mean difference of 0.23 mm. The Pearson
      correlation coefficients were very high and similar to each other: R = 0.989 and
      R = 0.988 for the Anterior Bolton Index (ABI) and Overall Bolton Index (OBI),
      respectively. No statistically significant differences were present from either
      the ANOVA or the paired t-tests. CONCLUSION: The used digital method is as
      accurate as the traditional one, it is faster and easier to carry out and it
      offers all the advantages of image storage and data for subsequent use.

PMID- 24741802
TI  - The influence of functional therapy on facial and dental structures. Case
      presentation.
AB  - In the era of fixed appliances, some orthodontic practitioners seem to forget
      about functional therapy. Functional appliances are the only capable of
      orthopedically changes during the growth spurt. Activators of all types, classic
      or opened, are elected appliances in growing subjects with class II/1 anomalies.
      The appropriate case selection, along with patient compliance, lead to improved
      facial aesthetic and dental occlusion, at affordable prices. With this case
      presentation, we want to show our protocol in the management of these cases.

PMID- 24741803
TI  - Synthesis, characterization and antioxidant activity of some new thiazolidin-4
      one derivatives.
AB  - AIM: To design new thiazolidin-4-ones derivatives and to evaluate their potential
      antioxidant effects using in vitro methods. MATERIAL AND METHODS: New ethyl
      esters of the 2-(R-phenyl)-4-oxo-thiazolidin-3-yl propionic acid were synthesized
      using "one step reaction" between different aromatic aldehydes, thioglycolic acid
      and beta-alanine ethyl ester hydrochloride. The antioxidant potential of the
      synthesized compounds was evaluated using the DPPH radical scavenging assay and
      phosphomolybdenum method. RESULTS: Eight thiazolidine-4-one derivatives were
      obtained in good yields and high purity. The structure of the synthesized
      compounds was confirmed using IR spectroscopy. The evaluation of antioxidant
      activity showed that 2-[(4-NO2)-phenyl]-4-oxo-thiazolidin-3-yl propionic acid
      ethyl ester (compound 16) was the most active compound. For this derivative the
      DPPH radical scavenger activity (I% = 91.63% +/- 0.77) and the total antioxidant
      capacity (absorbance = 1.0691 +/- 0.0763) were similar with that of ascorbic acid
      used as standard antioxidant. CONCLUSIONS: The antioxidant activity of the
      thiazolidine-4-one derivatives depends on the nature of the phenyl ring
      substituents, the NO2 and OH radicals having the most significant influence.

PMID- 24741804
TI  - Development and optimization of the synthesis of new thiazolidin-4-one
      derivatives of ibuprofen.
AB  - Ibuprofen, an important nonsteroidal anti-inflammatory agent, is one of the most
      prescribed drugs for the treatment of pain and inflammation from various
      rheumatic diseases, but some side effects can occur on long-term use. AIM: The
      method for synthesis optimization of new derivatives of Ibuprofen with
      thiazolidin-4-one moiety, with improved pharmacological and toxicological
      profile. MATERIAL AND METHODS: To optimize the derivatization method of free
      carboxyl group of Ibuprofen (2-(4-isobutylphenyl)propionic acid) the reaction
      conditions were varied (reagent ratio, catalyst, reaction medium). RESULTS: The
      most favorable method was proved to be the reaction between ibuprofen hydrazone
      and mercaptoacetic acid, in excess, at 80-85 degrees C, for 6 h with 96%
      conversion rate. CONCLUSIONS: The synthesis of 2-phenyl-3-[2-(4-(isobutyl)phenyl)
      2-methyl]acetamido-thiazolidin-4-one derivative was optimized in view of applying
      it as a general procedure for the synthesis of other derivatives with related
      structure. The chemical structure and molecular weight of the synthesized
      compound were confirmed by spectral methods (IR, 1H NMR, 13C NMR, HR-MS).

PMID- 24741805
TI  - Research studies on in vitro and ex vivo yield of the miconazole nitrate from
      oral biomucoadhesive tablets.
AB  - Among the various routes of drug administration, the oral mucosa is perhaps the
      most often preferred by patients and medical staff. However, oral administration
      of drugs has disadvantages, which may limit or prevent oral administration of
      some drugs, especially peptides and proteins, little when they are inserted in
      special administration systems for the colon. The disaggregation of some oral
      biomucoadhesive tablets and the in vitro yield of the miconazole nitrate was
      evaluated and in parallel with this, the evaluation of the in vivo yield of the
      antifungal from the pharmaceutical form. Thus, for a clear determination of the
      oral mucobioadhesive tablets' disintegration with miconazole nitrate, it was
      necessary to implement a method to simulate the conditions of the oral cavity at
      a flow of solution (artificial saliva) similar to that of the human one.
      MATERIALS AND METHODS:  MATERIALS: miconazole nitrate. METHODS: The determination
      of disintegration time according to method A (FRX); the disaggregation of oral
      biomucoadhesive tablets with miconazole nitrate by means of simulation methods of
      in vitro conditions; the quantitative determination of the miconazole nitrate by
      means of HPLC method, after the in vitro dissolution test; the study of
      miconazole nitrate's yield in dynamic condition from biomucoadhesive tablets in
      the presence of artificial saliva (AFNOR). RESULTS: The yield profile of the
      miconazole nitrate in the disintegration solutions by means of classical method
      from FR X, by HPLC dosage was researched. The release of miconazole nitrate from
      the oral mucobioadhesive tablets was determined, that varies in time, depending
      on the type and relation of matrix forming polymers; a low yield speed of the
      miconazole nitrate from the tablets was determined; the yield profile of
      miconazole nitrate in disintegration solutions by means of the new suggested
      method was researched. CONCLUSIONS: The release of miconazole nitrate from the
      formulated biomucoadhesive tablets is of swelling and erosion.

PMID- 24741806
TI  - Effects of perfluorocarbon emulsion in rheology.
AB  - AIM: To study effects of a perfluorocarbon emulsion on plasma and whole human
      blood viscosity in the presence of albumin or modified fluid gelatin. MATERIAL
      AND METHODS: We investigated the effects of several PFC concentrations on plasma
      and whole blood viscosity in the presence of human albumin solution (HAS) or
      modified fluid gelatine (MFG; Gelofusine) to obtain three PFC emulsion
      concentrations (4, 8 and 15 g/dL). Three hematocrit levels (Hct) were
      investigated: 30, 20 and 13%, corresponding to different clinical situations.
      Plasma and whole blood viscosity was measured at 37 degrees C, using a Couette
      viscometer for shear rates ranging from 0.2 to128 s(-1). RESULTS AND DISCUSSION:
      All PFC concentrations increased plasma and whole blood viscosity for the same
      Hct. Viscosity values similar to physiological ones were observed at Hct 13%,
      with MFG - PFC 4, 8 g/dL and HAS - PFC 15 g/dL; at Hct 20%, with MFG - PFC 4g/dL
      and HAS - PFC 15 g/dL; at Hct 30%, and HAS - PFC 4, 8 g/dL. CONCLUSIONS: We
      conclude that this PFC emulsion increases plasma and blood viscosity and that
      among the three studied volume expanders, the interaction with MFG can result in
      viscosity values above the physiological one even at low Hct values. Our results
      suggest that such increased blood viscosity could decrease skeletal muscle oxygen
      pressure.

PMID- 24741807
TI  - Evaluation of free radical scavenging activity of some antioxidants.
AB  - Measurement of free radical scavenging capacity of antioxidants is influenced by
      a number of parameters that depend on reaction rate. AIM: A new method for
      assessing the free radical scavenging activity in which the influence of
      antioxidant concentration and reaction rate on chlorpromazine radical cation
      absorbance are simultaneously monitored. MATERIALS AND METHODS: The change in
      radical solution absorbance at 525 nm within a fixed time at different
      concentrations of the standard antioxidant--ascorbic acid (AA) are determined and
      percent inhibition is calculated. RESULTS: The percent inhibition of color was
      plotted versus time, and the area under the curve was calculated for each
      concentration of the standard antioxidant. The calibration curve was obtained by
      plotting the area under the curve versus ascorbic acid concentration. The
      antioxidant activity of the samples was calculated using the regression line
      equation (r2 = 0.9991) and expressed as ascorbic acid molar equivalents (AAE)
      depending on the unit of measurement chosen for the tested product. CONCLUSIONS:
      The proposed method takes into account the two parameters influencing the
      kinetics of the reaction between antioxidant and radicals, namely the antioxidant
      concentration and fixed time for measuring absorbance.

PMID- 24741808
TI  - Possibilities to acylate 7-aminocephalosporanic acid to obtain some
      cephalosporins.
AB  - AIM: Acylation of 7-aminocephalosporanic acid with an adequate acyl chloride in
      order to obtain cefotaxime sodium salt. MATERIAL AND METHODS: Cefotaxime sodium
      salt was synthesized by acylating 7-amino cephalosporanic acid with 2-[2'
      chloracetamidothiazole-4-yl]-2-(syn)-methoxy-imino acetic chloride in four steps.
      The melting point was determined, and IR spectral analysis and elemental analysis
      were performed to confirm cefotaxime structure. The quantitative determination
      was performed. RESULTS: The reaction conditions were established. The yield of
      the synthesis phases (73-80%) and actual yield (45-47%) were very good. The
      structure of the obtained cefotaxime sodium salt was confirmed by the IR spectral
      analysis and by elemental analysis (C, H, N). The melting point was 163 degrees
      C. The purity of the synthesized cefotaxime sodium salt was 98.9%. CONCLUSIONS:
      Cefotaxime sodium salt was synthesized by acylation of 7-aminocephalosporanic
      acid with 2-[2'-chloracetamidothiazole-4-yl]-2-(syn)-methoxy-imino acetic
      chloride, in aqueous solution, then transformed into sodium salt with sodium 2
      ethylhexanoate. The method proved to be very good, yields were good, it is
      reproducible and simple, and does not involve high risks, so it is also safe.

PMID- 24741809
TI  - Nonconventional techniques for separation of biosynthetic amino acids.
AB  - Amino acids can be obtained by biosynthesis, by protein hydrolysis or by
      extraction from natural sources. The most efficient methods are the first two,
      but the separation of amino acids from fermentation broths or protein
      hydrolysates is rather difficult. Amino acids dissociate in aqueous solutions,
      forming characteristic ionic species depending on the solution pH-value. These
      properties make amino acids to be hydrophilic at any pH-value. This paper
      presents a review of the separation studies of some amino acids by
      nonconventional methods, namely individual or selective reactive extraction.
      Separation of some amino acids from their mixture obtained either by fermentation
      or protein hydrolysis by reactive extraction with different extractants indicated
      the possibility of the amino acids selective separation as a function of the pH
      value of aqueous solution correlated with the acidic or basic character of each
      amino acid.

PMID- 24741810
TI  - [The good death].

PMID- 24741811
TI  - [Beeswax - enveloping warming cover].

PMID- 24741812
TI  - [Prevention of ventilator-associated pneumonia: what has changed due to the new
      Robert Koch Institute guideline? (interview by Hardy-Thorsten Panknin)].

PMID- 24741813
TI  - [Psychological experiences and coping strategies of children and adolescents with
      chronic kidney disease on renal replacement therapy].
AB  - Children, adolescents and young adults with end-stage renal disease need a renal
      replacement therapy (dialysis) or a renal transplant to survive. The dialysis is
      related to a very complex care, which includes invasive and painful procedures.
      Chronic diseases have a strong influence not only on the physical but also on the
      psychological development of children and adolescents. The most important
      psychological consequences include social isolation, differences in body image,
      limited lifestyle, as well as the changed personal relationships with family and
      friends. Therefore, caregivers should also have knowledge about the psychological
      consequences, being able to provide adequate help and support to children,
      adolescents and young adults.

PMID- 24741814
TI  - [Child health depends on the living environment. Neighborhood is more important
      than social status of the family].

PMID- 24741815
TI  - [Vacation without suitcase. Experiencing inclusion!].

PMID- 24741816
TI  - ["Assessment of cancer-induced fatigue by nurses and patients in pediatric
      oncology"].

PMID- 24741817
TI  - [Control and care of risk newborn infants. Legal liability decisions].

PMID- 24741818
TI  - [Excellent. For children 2014 - 2015].

PMID- 24741819
TI  - [German Copper Institute sponsors a workshop during the 12th Congress for
      Hospital Hygiene of the DGKH. Expanding hygiene concepts: using potential
      antimicrobial copper materials].

PMID- 24741820
TI  - [Team work and networking].

PMID- 24741821
TI  - [The Robiliard report for psychiatry is well received].

PMID- 24741822
TI  - [A thunderbolt from a serene sky].

PMID- 24741823
TI  - [The psychopathology of acute and transient psychotic disorder].
AB  - Acute and transient psychotic disorder remains an important element of the
      clinical field. It was first observed by Philippe Pinel in the 19th century.
      Other figures, such as Philippe Chaslin and Valentin Magnan, have contributed to
      the identification of the disorders and a psychopathological classification.
      While the central clinical element of acute and transient psychotic disorder is
      delusion and hallucinations, its resolution can be quick or it may be a sign of
      the gradual onset of a psychiatric pathology.

PMID- 24741824
TI  - [Acute and transient psychotic disorder at the onset of schizophrenia].
AB  - Although the mode of onset of schizophrenia can be acute, it is important to
      remember that the disorder rarely starts as a "clap of thunder in a quiet sky",
      and that it is more often gradual and insidious, with negative and affective
      symptoms. Acute and transient psychotic disorder, on the other hand, is a short
      delusional episode forming suddenly and lasting a few days, sometimes a few
      hours. Schizophrenic evolution forms only part of the possible evolutions. It is
      therefore necessary to disassociate acute and transient psychotic disorder from
      schizophrenic disorders, which gives a wrong representation of the onset of
      schizophrenia.

PMID- 24741825
TI  - [Nursing care of acute and transient psychotic disorder].
AB  - Around the clinical situation of a patient presenting an acute and transient
      psychotic disorder, the importance of team work becomes evident. Nursing care is
      present in all phases of the patient's care, from admission to discharge,
      including in the isolation room and the electroconvulsive therapy sessions.
      Presence, support, reassurance as well as the bond with the family are
      cornerstones of the nursing care.

PMID- 24741826
TI  - [Lifting the curtain on improvisation as a method].
AB  - On the care stage, all the actors are active. One comes to lay down their
      suffering, the other has a dutyto consider their pain. The caregiver must play a
      role in stage managing the patient from the moment he or she remains anchored in
      reality and in the present moment. Beyond listening to the delusional speech,
      beyond containment and the effort of establishing communication, the nursing care
      of delusional patients falls within the sphere of negotiation.

PMID- 24741828
TI  - [Bibliography].

PMID- 24741827
TI  - [The onset of illness: "it will blow over"].
AB  - The onset of the illness of a friend or family member does not always present
      strong clinical signs such as acute and transient psychotic disorder. It is
      sometimes insidious. For families, this period is punctuated with fears and
      hopes. Delusional disorders turn familiar reference points on their head and
      although the first contact with the universe of the psychiatric hospital remains
      painful, the institution can be reassuring for families. This article presents a
      moving testimony of a parent and member of the French National Union of the
      Friends and Families of Mental Health Patients (UNAFAM).

PMID- 24741829
TI  - [Communicating effectively: neuro-linguistic programming in the psychiatric
      interview].
AB  - Neuro-linguistic programming is a set of practices and knowledge which seeks to
      "model" and then imitate the best communication practices. Applying the key
      concepts to the care relationship in mental health care helps to improve the
      quality of the contact, the clarity of the communication and to create an
      openness to change.

PMID- 24741830
TI  - [Pathological gambling and addiction to cannabis: common psychosocial profile?].
AB  - Addiction can involve substances (heroin, cannabis, cocaine) or be characterised
      by behaviour (pathological gambling, addiction to sport, etc.). The question is
      to establish whether or not there is a specific personality profile (character,
      temperament) and emotional functioning (anxiety, depression, alexithymia) in
      subjects presenting addictive behaviour with and without substance use. To find
      some answers, a team from Sainte-Marguerite General Hospital in Marseille carried
      out a study comparing a group of cannabis addicts and a group of pathological
      gamblers.

PMID- 24741831
TI  - [Georges Devereux].

PMID- 24741832
TI  - Current state of psychiatry in Saudi Arabia.
AB  - BACKGROUND: In 1983, an article and accompanying editorial was published on the
      state of psychiatry in the Kingdom of Saudi Arabia (KSA), which was described as
      "a mental health system in statu nascendi." METHODS: We provide a 30-year update
      on advances in mental health care in KSA. Data are reported from a wide range of
      sources, including the 2007 Saudi Arabian Mental and Social Health Atlas, which
      compares services in KSA with the rest of the world. RESULTS: We examine how the
      current mental health system operates in KSA, including recent changes in mental
      healthcare policy and development of a national mental healthcare plan. Discussed
      are current needs based on the prevalence and recognition of mental disorders;
      availability of services and providers (psychiatrists, psychiatric nurses,
      psychologists, and social workers); education and training in psychiatry;
      developments in consultation-liaison, addictions, child-adolescent, and geriatric
      psychiatry; and progress in mental health research. CONCLUSIONS: Mental
      healthcare in Saudi Arabia has come a long way in a very short time, despite
      cultural, religious, social, and political challenges, although there still
      remain areas where improvement is needed. The development of psychiatry in KSA
      serves as a model for countries in the Middle East and around the world.

PMID- 24741833
TI  - Parenting stress and dimensions of parenting behavior: cross-sectional and
      longitudinal links with adolescents' somatization.
AB  - OBJECTIVE: This study explored direct and indirect associations between
      adolescents' somatization, parenting stress, and three parenting dimensions
      (warmth, psychological control, and harsh punishment). First, the associations
      were explored cross-sectionally. Second, significant cross-sectional links were
      further examined longitudinally in order to decide upon temporality. METHOD: A
      total of 1499 adolescents and one of their parents (mostly the mother) agreed to
      participate. Questionnaires were administered when the child was respectively 12
      13 (T1), 13-14 (T2), and 14-15 (T3) years old. Adolescents reported on their
      somatization, parents on their parenting behavior and parenting stress. RESULTS:
      Cross-sectionally, indirect links were found between all parenting dimensions and
      adolescents' somatization, through parenting stress. Longitudinal examination
      revealed two key aspects. First, parenting stress significantly predicted
      somatization. Higher T1 parenting stress was predictive for higher T2 and T3
      somatization. When controlled for T1 parenting stress, higher T2 parenting stress
      (or in other words increased parenting stress at T2) was predictive for lower T3
      somatization. Second, parenting stress was found to significantly predict
      parenting behaviors. Higher T1 parenting stress was predictive for higher T2 and
      T3 harsh punishment but increased parenting stress at T2 was predictive for lower
      harsh punishment one year later. Higher T1 parenting stress significantly
      predicted higher T2 psychological control. CONCLUSIONS: Clinicians should be
      aware that parenting stress may be a risk factor for the development of
      somatization in early adolescence. However, in later adolescence, increased
      parenting stress might be protective.

PMID- 24741834
TI  - Control strategies and suicidal ideation in older primary care patients with
      functional limitations.
AB  - OBJECTIVES: Failure to adapt to limitations in control may place older adults at
      risk for suicidal behavior. The present study examined the relation between
      control strategies, depressive symptoms, and suicidal ideation in older adults
      with health-related limitations. METHODS: Cross-sectional study of 50 older adult
      (aged 65-94) primary care patients with health-related limitations. RESULTS:
      Compensatory primary control strategies characterized by seeking help from others
      were associated with lower levels of suicidal ideation, independent of depressive
      symptoms. Selective primary control strategies (e.g., persistence) were also
      associated with reduced suicidal ideation independent of depressive symptoms, but
      only when a low level of compensatory primary control strategies was endorsed.
      Selective secondary control strategies were associated with higher suicidal
      ideation, whereas compensatory secondary control strategies (e.g., goal
      disengagement) were unrelated in this sample after controlling for covariates.
      CONCLUSIONS: Findings demonstrate that primary care patients with functional
      limitations who are not striving to meet their goals, either through persistence
      or by seeking help from others, are at elevated risk of suicidal thinking.

PMID- 24741835
TI  - Sleep quality among primary care attendees in Kaduna, Northern Nigeria: a case
      control study.
AB  - OBJECTIVE: To assess sleep quality and its determinants among primary care
      patients in a Northern Nigerian setting. METHODS: We administered the Pittsburgh
      Sleep Quality Index (PSQI) and the Hospital Anxiety and Depression Scale to 217
      consecutive patients attending the General Outpatient Clinic of Barau Dikko
      Specialist Hospital, Kaduna, and PSQI to 223 age-matched controls to evaluate
      their sleep quality and levels of anxiety and depression. A data collection sheet
      was used to record the sociodemographic characteristics of patients and controls,
      and the clinical characteristics of the patients. RESULTS: The mean ages of all
      the subjects, patients, and controls were 33.7 (SD 10.6), 33.5 (SD 10.6), and
      34.0 (SD 10.5) years respectively; 54.4% of the patients were females, 54.8% were
      Muslims, 56.2% admitted they had pain, 60.8% and 46.5% had anxiety and depressive
      symptoms respectively, while 68.7% had poor sleep quality. The mean global score
      of sleep quality for patients was 9.2 (SD 3.6) while that of the control was 3.8
      (SD 1.4). The difference was statistically significant (t = 20.834, P value <
      0.001, 95% CI 4.891-5.910). Islamic religious faith, presence of pain, anxiety
      symptoms, and depressive symptoms were significantly associated with poor quality
      of sleep (P value < 0.05). Multiple regression analysis identified being a Muslim
      (OR 6.422, P value 0.027, 95% CI 0.196-0.907), pain (OR 8.038, P value < 0.001,
      95% CI 0.016-0.091), and anxiety symptoms (OR 5.253, P value < 0.001, 95% CI
      0.136-0.473) as predictors of poor sleep quality among the patients. CONCLUSION:
      Poor quality of sleep is common in primary care patients. Efforts should be made
      to improve its recognition, identify associated factors, and consider a holistic
      approach to patients' care.

PMID- 24741836
TI  - Physician wellness in rural America: a review.
AB  - OBJECTIVE: The primary purpose of this article is to review the unique wellness
      factors that affect physicians practicing in rural communities. Research has
      indicated that rural communities often struggle to attract and retain primary
      care physicians and numerous wellness factors impact these attraction/ retention
      rates. METHOD: Articles selected for inclusion in this review were determined
      based upon their relevance to rural physicians, overall wellness factors of
      physicians, and recruitment and retention of physicians in rural communities.
      Articles were included from peer-reviewed journals focusing upon both medical and
      psychological perspectives of rural physician wellness factors. RESULTS: Results
      indicated that rural physicians often have fewer resources, an increased
      workload, and longer hours when compared to their urban counterparts. These
      factors contribute to lower job satisfaction, poor retention rates, and decreased
      physician wellness. Research also demonstrates that physicians who are unwell are
      more likely to experience substance abuse, depression, relationship difficulties,
      and general psychological distress. These issues are particularly prominent in
      rural practice settings and may have significant impact upon rural patients.
      CONCLUSION: To date, there are few assessment measures available to assess
      physician wellness and no evidence-based treatments to address wellness deficits
      in rural physicians' medical or psychological health. Such resources would have
      the potential to benefit individual rural physicians and the quality of
      healthcare they deliver to rural communities. Future research should focus upon
      the assessment and promotion of rural physician well being, which may improve
      recruitment and retention of quality physicians to provide optimal care in rural
      communities.

PMID- 24741837
TI  - Can hoarding be a symptom of social anxiety disorder? A case study.
AB  - BACKGROUND: Hoarding is defined as the excessive collection and failure to
      discard possessions of apparently little value, leading to clutter, distress, and
      disability. Although patients with hoarding typically may feel ludicrous for not
      discarding useless, and sometimes bizarre, possessions, we are not aware of any
      previous description of patients displaying hoarding as a result of social
      anxiety. METHOD: Single case report. RESULTS: In this article, we describe a
      patient with severe social anxiety disorder who displayed hoarding as a direct
      consequence of social anxiety-related beliefs and atypical safety behaviors.
      CONCLUSIONS: This case is of particular interest to current debates concerning
      the status of hoarding in new versions of classificatory systems. It also
      indicates that social anxiety disorder should be included in the list of
      conditions that needs to be excluded in order to diagnose "primary" hoarding
      disorder.

PMID- 24741838
TI  - "Substance and physical abuse: the effects on oral health".

PMID- 24741839
TI  - SADA endorces fluoridation.

PMID- 24741840
TI  - A new society offers new horizons.

PMID- 24741841
TI  - Substance abuse and oral health: an overview.
AB  - Substance abuse is a worldwide phenomenon. It is on the increase in most
      countries and claims the lives of millions every year. Substance abuse may
      involve licit and illicit drugs, with licit substances claiming more lives than
      illicit drugs. Illicit substance abuse is on the increase, especially with new
      drugs emerging on the world market every year. These new drugs appear faster than
      scientific studies can keep pace in determining their possible detrimental
      influences on health. Many abused drugs do have oral health complications. For
      this reason, it is important for dentists to have a thorough knowledge of the
      oral environment to be able to detect any abnormalities, regardless of what the
      underlying cause may be. Due to the nature of illicit substance abuse, reliable
      information and science is hard to come by. This overview will focus on the
      direct consequences for oral health, whilst acknowledging that substance abuse
      may also have direct and indirect influences on general health.

PMID- 24741842
TI  - Prosthetic challenges in a patient with ocular evisceration and global
      preservation: a case report.

PMID- 24741843
TI  - Probiotics and oral health: an update.
AB  - Probiotics are micro-organisms, principally bacteria, which, when ingested,
      confer health benefits beyond basic nutrition. Probiotics have been extensively
      studied for their health promoting effects. The main feld of research has been
      focussed on the gastro-intestinal tract. However, in the past few years
      probiotics have also been investigated from an oral health perspective and their
      use has shown promising results with respect to control of chronic conditions,
      such as dental caries, periodontitis, halitosis and candidial infections. Despite
      the immense potential of probiotics, hardly any randomised, controlled trials
      have been conducted on their action and application and studies on their effects
      on oral health are still in early stages. Hence, more research is needed before
      any evidence-based conclusions can be drawn. This paper considers some recent
      literature and insights on which further investigations could be based.

PMID- 24741844
TI  - Maxillo-facial radiology case 117. Systemic sclerosis (scleroderma).

PMID- 24741845
TI  - Oral medicine case book 56: Oral manifestations of aplastic anaemia.

PMID- 24741846
TI  - Xenografts and religious beliefs.

PMID- 24741847
TI  - [Personalized medicine on the upswing].

PMID- 24741848
TI  - [The multiple myeloma--current view and perspectives].
AB  - The multiple myeloma (MM) is still an incurable malignant plasma cell disease.
      Therapy is necessary, once symptoms of end organ damage occur. Numerous ",new
      substances" (proteasome inhibitors, immunomodulatory substances) were introduced
      in the past decade, resulting in improved treatment results. Polychemotherapy,
      alternating drug applications and the principle of "continuous therapy" are used
      to achieve a high response rate (with the aim of a long-lasting disease control).
      Among all patients those with extramedullary disease (EMD) are currently the most
      difficult treatable patients. It remains to be seen whether and when genomic
      analyses by next generation sequencing will yield to an understanding of the ups
      and downs of various tumor subclones. Maybe such technologies result in the
      development of real targeted therapies for myeloma in the future. To date, such
      therapies are not available.

PMID- 24741849
TI  - [Dextromethorphan abuse in adolescents: what can the pharmacists do?].
AB  - In Germany, dextromethorphan (DXM) is used as OTC cough and cold medication.
      Overdose, however, can cause psychotropic side effects and is therefore abused
      among adolescents. To better control the drug by the pharmacist, a pilot was
      undertaken to monitor drug selling of DXM in German retail pharmacies. Over a 6
      month period, pharmacies documented the request of DXM preparations. These data
      were compared to abuse cases of the German regulatory agency, the Bundesinstitut
      fur Arzneimittel und Medizinprodukte (BfArM), an analysis of the 2010 annual
      sales statistic from the IMS OTC and information about DXM products from drug
      abuse websites. Especially the young DXM buyers in German retail pharmacies
      showed characteristics similar to those people from the BfArM abuse data file:
      They were male and used the DXM product Hustenstiller-ratiopharm. Hustenstiller
      ratiopharm has well-directed instructions for DXM abuse in the internet. However,
      the 2010 annual sales statistic from the IMS OTC report identified Wick MediNait
      as the product with highest sales numbers whereas Hustenstiller-ratiopharm" was
      of less importance indicating DXM abuse is limited to a small part of the DXM
      user population.

PMID- 24741850
TI  - ["Next-generation" sequencing. Integration of personalized medicine into clinical
      care].

PMID- 24741851
TI  - [Do prenatal probiotics lower the risk for the development of atopic eczema in
      children?].

PMID- 24741852
TI  - [Macrogol improved constipation, but not the quality of life].

PMID- 24741853
TI  - Early diurnal variation of serum leptin and adiponectin in nontreated obstructive
      sleep apnea disease: a prospective observational study.
AB  - BACKGROUND: Obstructive sleep apnea (OSA) is a common disorder resulting in a
      myriad of adverse vascular risks, including altered inflammatory/anti
      inflammatory adipokine balance. Recent studies are yet to agree on how this
      balance responds to the OSA severity. As it is customary in these studies to
      obtain a single blood sample in participants after completion of the nocturnal
      polysomnogram (PSG), we hypothesized that these adipokines' early ultradian
      pulsatility might contribute to the reported contradictory results. METHODS:
      Fasting serum leptin and adiponectin were measured every 15 minutes for one hour
      in the morning after the diagnostic PSG for 13 adults recruited consecutively
      from the Salem VAMC Sleep Clinic between September 2006 and October 2007.
      RESULTS: No differences in the timed paired samples of leptin (P = 0.30) and
      adiponectin (P = 0.28) were found in OSA participants (mean apnea-hypopnea index
      21.1). CONCLUSION: Customary protocol of obtaining a single blood sample for
      leptin and adiponectin after nocturnal PSG seems appropriate.

PMID- 24741854
TI  - Western variant of brain intravascular lymphoma displaying three distinct
      evolutive radiologic stages.
AB  - Intravascular lymphoma is a rare type of extranodal diffuse large B-cell lymphoma
      characterized by proliferation of clonal lymphocytes within small- and medium
      sized blood vessels and a relative sparing of surrounding tissues. It commonly
      affects the central nervous system (CNS), but its atypical presentation often
      leads to a delayed diagnosis. We report a unique case of a 53-year-old man
      presenting with confusion and ataxic gait. The initial magnetic resonance imaging
      (MRI) of the brain showed multifocal plaque-like CNS lesions suggestive of
      multiple sclerosis. His condition worsened rapidly, accompanied by persistent low
      grade fever and further alteration in mental status. Follow-up MRI studies
      suggested new parenchymal brain lesions consistent with multiple evolving embolic
      strokes and subsequently with brain infarcts. Biopsy showed intravascular
      lymphomatous brain involvement. His condition continued to deteriorate, resulting
      in multiorgan failure and demise. To the best of our knowledge, these clear-cut
      MRI stages of brain intravascular lymphoma have not been previously reported in
      the scientific literature. Our findings are important as the diagnosis
      intravascular lymphoma is commonly made postmortem, given its rapidly progressive
      course and lack of typical symptomatology.

PMID- 24741855
TI  - Reactivation of pulmonary tuberculosis following local radiation therapy of
      prostate cancer.
AB  - In this report, we describe the case of an 81-year-old male with reactivation
      tuberculosis following local radiation therapy for prostate cancer. The patient
      was asymptomatic except for an unintentional 20-pound weight loss and was
      incidentally found to have a pulmonary infiltrate in the right upper lobe on
      imaging for shoulder pain. The medical history was not able for recently treated
      prostate cancer. After further investigation, the patient was determined to have
      Mycobacterium tuberculosis infection. It is important to have a high level of
      suspicion for reactivation tuberculosis in patients with a pulmonary infiltrate
      following radiation therapy due to the impact of radiation on the host's immune
      system. We will review the literature on reactivation tuberculosis following
      radiation therapy and explore the mechanism of immunosuppression in this process.
      To our knowledge, this is the first reported case of tuberculosis reactivation
      following local radiation therapy for prostate cancer.

PMID- 24741856
TI  - Disulfiram--alcohol reaction mimicking an acute coronary syndrome.
AB  - Disulfiram treatment for alcohol dependence is used with acceptable outcomes. By
      inhibiting the aldehyde dehydrogenase enzyme, this treatment increases
      acetaldehyde concentration after the ingestion of alcohol causing an unpleasant
      disulfiram-alcohol reaction. Typical symptoms include flushing, headache, nausea,
      vomiting, sweating, vertigo, and lightheadedness. However, there have also been
      descriptions of more serious reactions including severe hypotension, arrhythmias,
      myocardial infarction, and cardiovascular collapse. We report a patient with a
      severe disulfiram-alcohol reaction marked by flushing, confusion, generalized
      malaise, epigastric pain, and hypotension. Cardiac biomarker and
      electrocardiographic changes were suggestive of non-ST-elevation myocardial
      infarction (NSTEMI). Left heart catheterization showed no angiographic evidence
      of coronary artery disease. Because of the frequency of alcohol dependence and
      its treatment with disulfiram, it is critical for physicians to be aware of these
      types of life-threatening complications.

PMID- 24741857
TI  - Warthin's tumor with superimposed mycobacterium tuberculosis infection.
AB  - We report a case of atypical mycobacterium infection in a Warthin's tumor which
      occurred in a 79-year-old man. The patient had along history of a left parotid
      mass that underwent rapid growth, became painful, and fistulized. The patient
      underwent left parotidectomy and neck dissection which showed a Warthin's tumor
      with areas of necrotizing granulomas. Subsequent culture showed the growth of
      acid fast bacilli. Consideration of an underlying mycobacterium infection,
      although rare, is important due to the public health concerns and other treatment
      needs that such a diagnosis raises.

PMID- 24741858
TI  - Costs of non-helmeted motorcycle riding in Connecticut.
AB  - Motorcycle-related head injuries and fatalities are a serious public health
      concern that can be reduced with helmet use. Caring for crash victims places
      additional economic stress on the healthcare system. The current Connecticut
      motorcycle helmet law does not require all motorcyclists to wear helmets.
      Universal motorcycle helmet laws increase helmet use. Efforts to increase helmet
      use through education and legislation should be considered for review, given the
      number of deaths and injuries that could be prevented.

PMID- 24741859
TI  - Medical malpractice reform: more choices for improvement.

PMID- 24741860
TI  - Annular pancreas.

PMID- 24741861
TI  - Dealing with disciplinary hearings before Connecticut's Department of Public
      Health.

PMID- 24741863
TI  - The revival of house calls.

PMID- 24741862
TI  - Delirium in hospitalized patients: recognition, prevention, and management.

PMID- 24741865
TI  - (Can't get no) satisfaction.

PMID- 24741864
TI  - The Connecticut Registry--its importance and contributions to oncology. 1964.

PMID- 24741866
TI  - The more things change.

PMID- 24741867
TI  - Shifting the liability paradigm.

PMID- 24741868
TI  - APRN scope of practice: additional opinions.

PMID- 24741869
TI  - APRN scope of practice: additional opinions.

PMID- 24741870
TI  - APRN ccope of practice: additional opinions.

PMID- 24741871
TI  - "Staff need to know it's safe to speak out".

PMID- 24741872
TI  - Not there yet on raising concerns.

PMID- 24741873
TI  - Wilful neglect offence to cover all settings.

PMID- 24741874
TI  - Hospital and community trusts lead on pledge to protect staff.

PMID- 24741875
TI  - Major study confirms benefit of move to graduate nursing.

PMID- 24741876
TI  - Lack of staff stops three in four nurses from working effectively.

PMID- 24741877
TI  - "Many staff across the UK are still too afraid to raise concerns".

PMID- 24741878
TI  - "Think of a world without any ... diabetes specialist nurses".

PMID- 24741879
TI  - Reducing admissions for people with diabetes.
AB  - Reversing the rise in emergency hospital admissions is an NHS priority. These
      admissions impact on elective capacity and waiting times and are unsustainable.
      The risk of hospitalisation for people with diabetes is almost twice that for
      others. Commissioners need to address admissions associated with diabetes and new
      guidance offers best-practice solutions.

PMID- 24741880
TI  - Management of diabetic ketoacidosis in adults.
AB  - Ketoacidosis is a serious complication of diabetes. It is commonly precipitated
      by poor adherence to medication, stress and concurrent illness; it can be life
      threatening if it is not addressed quickly and effectively. This article
      discusses the pathophysiology, diagnosis and management of the condition, and
      highlights the nurse's role in this.

PMID- 24741881
TI  - Family presence at resuscitation attempts.
AB  - UK resuscitation guidelines suggest that parents and carers should be allowed to
      be present during a resuscitation attempt in hospital but no guidance is
      available regarding family presence when resuscitation takes place out of
      hospital. A new research study has suggested that relatives who were offered the
      opportunity to witness resuscitation were less likely to develop symptoms of post
      traumatic stress disorder than those who were not given the chance. This article
      summarises the results of this study and provides an expert commentary on its
      conclusions.

PMID- 24741882
TI  - Stress and coping strategies in renal staff.
AB  - There is much research into stress among nursing staff, but no comparisons of
      stress levels between doctors and nurses in nephrology. This study aimed to
      address this gap by looking at stress triggers in this specialty and comparing
      those of renal nurses with those of nephrologists to identify coping mechanisms.

PMID- 24741883
TI  - 60 seconds with Richard Knowles.

PMID- 24741885
TI  - Reviews of the literature: expected standards.

PMID- 24741884
TI  - Caring while camping.

PMID- 24741886
TI  - Developing and implementing a fluoride varnish programme for young children in
      Bradford, UK.

PMID- 24741887
TI  - The provision of dietary advice by dental practitioners: a review of the
      literature.
AB  - PURPOSE: The aim of this literature review was to examine the dietary advice
      practices of dentists and dental hygienists and to identify factors influencing
      whether practitioners provide dietary advice to patients. METHODS: A systematic
      search was carried out of the electronic databases CINHAL Plus, Medline via OVID
      and the Cochrane Library, using the search terms 'Diet', 'Nutrition', 'Dental
      hygienists' and 'Dentists'. Articles included in the review were all empirical
      studies and existing literature reviews examining the provision of dietary advice
      practices of dentists, dental hygienists and dental students. Only articles
      published after 1993 were included in the review to better reflect the current
      practices of dental practitioners. RESULTS: The literature revealed that dietary
      advice is rarely provided by dental practitioners, and that when dietary advice
      is provided it is often limited. The literature also established that provision
      of dietary advice is influenced by a number of factors, including financial
      considerations, time constraints and the dietary education of dental
      practitioners. CONCLUSIONS: Further research is required to strengthen the
      findings from the review and to investigate dietary advice specific to the
      prevention of dental erosion. Additional research is also required to examine
      dental curricula and assess the dietary advice practices of dental students.

PMID- 24741888
TI  - Dentinal hypersensitivity: a narrative review.
AB  - INTRODUCTION: Dentinal hypersensitivity is an exaggerated response to a sensory
      stimulus that usually causes no response in a normal healthy tooth. It is a
      source of chronic irritation that can severely affect an individual's eating and
      drinking habits. The management of tooth hypersensitivity by oral healthcare
      professionals requires an appreciation of the complexity of the problem together
      with knowledge of available treatments. AIM: To review the symptoms, contributing
      oral factors, prevalence, measurement and mechanisms of dentinal
      hypersensitivity, together with current and potential future therapies for the
      condition. METHOD: Narrative literature review. PRINCIPLE FINDINGS: The
      permeability and fluid movement in open, exposed dentinal tubules has provided a
      favoured theory for stimulus transmission through dentine. Occlusion of dentinal
      tubules has been identified as a potential method of reducing pain associated
      with sensitive teeth. Current treatments work to occlude dentinal tubules.
      However these treatments can be expensive and their effects are often transient.
      In comparison, future therapies could be based upon either laser or iontophoresis
      techniques. CONCLUSION: Future therapies may provide a more permanent and cost
      effective way of treating dentinal hypersensitivity for health care professionals
      and their patients.

PMID- 24741889
TI  - Investigation of bias related to non-return of consent for a dental
      epidemiological survey of caries among five-year-olds.
AB  - Estimates of caries levels derived from an epidemiological survey of five-year
      olds in England were lower than expected. This survey used, for the first time, a
      consent method which involved parents providing positive, written consent for
      their child to be included in the survey. This contrasted to the previous method
      when negative consent was used. AIM: To interrogate the dataset to try and
      establish the reasons for the lower than expected estimates and explore the
      effect of non-return of parental consent, including the role of deprivation.
      BASIC RESEARCH DESIGN: Statistical analysis of an existing dataset and a sub-set
      of this dataset. MAIN OUTCOME MEASURES: Estimates of caries prevalence and
      severity in groups and sub-groups of a population-based, random sample of five
      year-olds. RESULTS: Hypotheses relating to possible changes in the process of
      data collection and analysis were rejected as reasons for the apparent reduction
      in disease estimates, as was the impact of oral and general health improvement
      programmes. Analysis of higher non-return levels on differences between past and
      current estimates and analysis of the associations between caries estimates, non
      consent and summed deprivation measures based on home postcodes showed some
      relationships between these variables but could not identify a simple
      relationship. CONCLUSION: There is a more complex relationship between non-return
      of consent and disease levels than can be explained by deprivation alone.

PMID- 24741890
TI  - Comparison of oral health among older people with and without dementia.
AB  - Older people with dementia are very dependent on nursing, and caregivers are
      frequently confronted with oral-care-resistant behaviour which may lead to
      shortcomings in oral health. OBJECTIVE: To compare oral hygiene and health status
      of institutionalised older people suffering, or not, from dementia. BASIC
      RESEARCH DESIGN: Prospective cohort study (single-blind). CLINICAL SETTING:
      Institutionalised older population in south-west Germany. PARTICIPANTS: Ninety
      three, allocated to two groups: dementia (n = 57) and non-dementia (n = 36) based
      on a mini mental state examination. MAIN OUTCOME MEASURES: Target variables were
      plaque control record (PCR), gingival bleeding index (GBI), community periodontal
      index of treatment needs (CPITN), and denture hygiene index (DHI). Differences
      between the dementia and non-dementia groups were evaluated by univariate testing
      of all target variables. RESULTS: Univariate analysis revealed the amount of
      plaque in the dementia group was significantly higher than in the non-dementia
      group (p = 0.004). Mean CPITN of participants in the dementia group was
      significantly worse than those of participants in the non-dementia group (p <
      0.001). All participants in the dementia group had periodontitis in at least one
      of the sextants, compared with 74% in the non-dementia group (p < 0.001). For DHI
      (p = 0.198) and GBI (p = 0.275) no differences were found between the groups.
      CONCLUSIONS: Some aspects of oral hygiene and health seem to be worse for the
      institutionalised older people with dementia. Permanent specially adapted
      intervention for residents suffering from dementia in long-term care homes, and
      training for caregivers, is desirable to maintain life-long oral hygiene and
      health.

PMID- 24741891
TI  - Mothers' sense of coherence and oral health related quality of life of preschool
      children in Udupi Taluk.
AB  - OBJECTIVE: To assess the relationship between mothers' Sense of Coherence (SOC)
      and oral health related quality of life (OHRQoL) of 3-5 year old preschool
      children in Udupi Taluk. PARTICIPANTS: 388 mothers aged 24-48 years old and their
      preschool children. BASIC RESEARCH DESIGN: A cross sectional study of mother
      child pairs, randomly selected from 8 preschools. METHOD: Information was
      obtained about mothers' sociodemographic factors along with the short version
      (SOC 13) of Antonovsky's sense of coherence scale and children's OHRQoL using the
      early childhood oral health impact scale (ECOHIS). Chi-square tests and
      multivariate logistic regression were used for analysis. MAIN OUTCOME MEASURES:
      Mothers' SOC and children's OHRQoL. RESULTS: Mothers' SOC and fathers' education
      were significantly associated with children's OHRQoL in multivariate analysis.
      Children of mothers with high SOC were 12.9 times as likely to have high OHRQoL
      as mothers with low SOC (p < 0.01). Children of fathers with college/university
      education were twice as likely to have high OHRQoL as those with primary
      education (p < 0.05). CONCLUSION: Our results suggest that mother's SOC could be
      a psychosocial determinant of the OHRQoL of their preschool children. Family
      environment should be considered when designing interventions to promote or
      improve the oral health as well as OHRQoL of preschool children.

PMID- 24741892
TI  - Development and psychometric validation of a Health Literacy in Dentistry scale
      (HeLD).
AB  - BACKGROUND: Oral health literacy is emerging as a new public health challenge and
      poor oral health literacy is increasingly seen as an important predictor of poor
      oral health outcomes. Within Indigenous populations, there may be benefits to
      research in using a culturally acceptable, internally consistent and valid
      instrument to assess oral health literacy. We translated a general health
      literacy measure, the Health Literacy Management (HeLM) scale to make a dentally
      relevant scale; Health Literacy in Dentistry (HeLD). OBJECTIVE: This study
      describes the development and assessment of the reliability and validity of the
      HeLD in an Indigenous Australian population. DESIGN AND METHODS: The 29 item HeLD
      scale assesses the components of oral health literacy. The reliability and
      validity of the seven HeLD subscales were evaluated in a convenience sample of
      209 Indigenous Australians with mean age 35 years (range 17-81) and of which 139
      were female. RESULTS: The scale was supported by exploratory factor analysis and
      established seven distinct and internally consistent domains of oral health
      literacy: Communication, Access, Receptivity, Understanding, Utilisation, Support
      and Economic Barriers (Cronbach's alpha = 0.91). Discriminative ability was
      confirmed by HeLD associations with socio-demographic variables and self-reported
      health ratings in the expected direction. The convergent validity and predictive
      validity were confirmed by HeLD scores being significantly associated with
      toothbrush ownership, use of a toothbrush, time since last dental visit and
      knowledge of the effect of cordial on the teeth. CONCLUSIONS: The HeLD appears to
      be an internally valid and reliable instrument and can be used for measuring oral
      health literacy among rural Indigenous Australian adults.

PMID- 24741893
TI  - Cross-cultural adaptation, validity and psychometric properties of the Spanish
      version of the Dental Satisfaction Questionnaire.
AB  - INTRODUCTION: No dental patient satisfaction questionnaires have been validated
      in Spain. OBJECTIVE: To validate in Spain a translated version of the Dental
      Satisfaction Questionnaire. METHODS: A consecutive sample of 217 patients
      attending the dental clinic of the University of Valencia was selected. The
      internal consistency of the questionnaire was analysed using Cronbach's alpha and
      the internal structure using principal components analysis. Its reproducibility
      was tested both by using the test-retest method with 31 patients randomly
      selected from the sample and by analysis using the absolute agreement intraclass
      correlation coefficient. RESULTS: Cronbach's alpha for the questionnaire was
      0.56. Seven principal components explain 60% of the variance. Test-retest
      obtained an intraclass correlation coefficient of 0.92 and the subscales obtained
      values higher than 0.7. DISCUSSION: The internal consistency of the scale is
      acceptable. The internal consistency of the pain management subscale is higher
      than that of the others. The original structure of five subscales is partially
      confirmed in our version because of quality and access subscales. The
      reproducibility is very good. Some items of Dental Satisfaction Questionnaire
      that show low consistency measure expectations that would have little effect on
      satisfaction scores. CONCLUSIONS: The Dental Satisfaction Questionnaire in
      Spanish can be considered an instrument for studying patient satisfaction in
      Spain as it has proved viable, has acceptable internal consistency and excellent
      reproducibility and covers different dimensions of the concept of satisfaction,
      such as pain management, accessibility, quality, availability/convenience and
      cost.

PMID- 24741894
TI  - The incidence of cleft lip and palate in a Kurd population: a prospective study.
AB  - AIM: To assess the incidence of cleft lip and palate and factors associated with
      them in the hospital births of Iran's Kurdistan province in 2010. METHODS:
      Researcher-completed questionnaires captured data on gender, mother's age during
      pregnancy, parents' occupation, father's birthplace, family background,
      consanguinity, systemic diseases, mother's disease during pregnancy, drugs abuse,
      smoking, alcohol drinking, radiography and mother's radiotherapy during
      pregnancy. RESULTS: Of 26,537 newborns, 29 (19 male and 10 females) were affected
      by various types of cleft lip and palate. Of newborns with cleft lip and palate:
      38% had other abnormalities, consanguinity was reported in about 31% of cases and
      28% of mothers used prescribed drugs during pregnancy while no mothers used
      cigarettes or alcohol. There was no report of radiotherapy or radiography.
      CONCLUSIONS: The incidence rate of oral clefts was 1.09 in the 1,000 live births.

PMID- 24741895
TI  - The significance of motivation in periodontal treatment: validity and reliability
      of the motivation assessment scale among patients undergoing periodontal
      treatment.
AB  - OBJECTIVE: The individual evaluation of patients' motivation should be introduced
      to the protocol of periodontal treatment, as it could impact positively on
      effective treatment planning and treatment outcomes. However, a standardised tool
      measuring the extent of periodontal patients' motivation has not yet been
      proposed in the literature. Thus, the objective of the present study was to
      determine the validity and reliability of the Zychlinscy motivation scale
      adjusted to the needs of periodontology. BASIC RESEARCH DESIGN: Cross sectional
      study. CLINICAL SETTING: Department of Periodontology and Oral Medicine, Dental
      University Clinic, Jagiellonian University, Krakow, Poland. PARTICIPANTS: 199
      adult periodontal patients, aged 20-78. INTERVENTIONS: 14-item questionnaire. The
      items were adopted from the original Zychlinscy motivation assessment scale. MAIN
      OUTCOME MEASURES: Validity and reliability of the proposed motivation assessment
      instrument. RESULTS: The assessed Cronbach's alpha of 0.79 indicates the scale is
      a reliable tool. Principal component analysis revealed a model with three
      factors, which explained half of the total variance. Those factors represented:
      the patient's attitude towards treatment and oral hygiene practice; previous
      experiences during treatment; and the influence of external conditions on the
      patient's attitude towards treatment. CONCLUSION: The proposed scale proved to be
      a reliable and accurate tool for the evaluation of periodontal patients'
      motivation.

PMID- 24741896
TI  - Oral health behaviours and perceptions reported by Indigenous Australians living
      in Darwin, Northern Territory.
AB  - OBJECTIVE: To describe the reported oral health behaviours and perceptions of
      Indigenous Australians living in Darwin, Northern Territory and to compare those
      with estimates for Darwin and Australia derived from the National Survey of Adult
      Oral Health (NSAOH). PARTICIPANTS: A total of 181 Indigenous Australians aged 22
      years and over living in Darwin, participating in screening for a wider
      randomised clinical trial, were included. METHOD: Information on socio
      demographic characteristics, oral health status including oral health behaviours
      and perceptions was collected using a questionnaire. Differences between the
      Darwin study (DS) participants and Australians in NSAOH were made based on non
      overlapping 95% confidence intervals. RESULTS: Almost 72% of DS participants had
      last seen a dentist over a year earlier, compared to 47% and 39% of NSAOH Darwin
      and Australian participants, respectively. A higher proportion of DS participants
      usually visited a dentist because of a problem than NSAOH Darwin and NSAOH
      Australian participants. A higher proportion of DS participants had avoided or
      delayed a dental visit because of cost than NSAOH participants. Over three times
      as many DS participants rated their oral health as fair/poor compared to NSAOH
      participants. A higher proportion of DS participants had perceived gum disease
      and one or more symptoms of gum disease than NSAOH participants. A higher
      proportion of DS participants experienced toothache, felt uncomfortable about
      appearance of their mouth and avoided eating because of oral problems than NSAOH
      participants. CONCLUSIONS: A higher proportion of Indigenous Australians living
      in Darwin presented with non-optimal oral health behaviours and perceptions
      compared with both the Darwin and Australian general populations.

PMID- 24741897
TI  - Trends in the geographic distribution of dental clinics in Japan.
AB  - AIM: In Japan, along with the increase in the number of dentists, the number of
      dental facilities has continuously increased as well. This study aimed to examine
      whether the increase in the number of dental clinics in Japan has led to an
      improvement in their geographic distribution. METHODS: We analysed the number of
      dental clinics and population in all municipalities in Japan as of 2000, 2005 and
      2010. We obtained data on the population from the population census and data on
      the number of dental clinics from the Survey of Medical Institutions. The number
      of municipalities was 3,258 in 2000 but had dropped to 1,750 by 2010 due to
      municipal mergers so population and dental data for other years were recalculated
      based on 2010 municipal boundaries. Lorenz curves and Gini coefficients were used
      to assess the distribution of dental clinics per 100,000 persons. RESULTS: The
      mean number of dental clinics per 100,000 persons among all municipalities was
      49.9 in 2000, 52.2 in 2005 and 53.4 in 2010. The Gini coefficient for the clinics
      in the whole country was 0.172 in 2000, 0.164 in 2005 and 0.153 in 2010.
      CONCLUSION: The results suggest that the regional inequalities in the
      availability of dentists have been reduced gradually as the number of dental
      clinics has increased.

PMID- 24741898
TI  - The professional dental assistant.

PMID- 24741901
TI  - Opportunity for dental assistants in the treatment of sleep apnea.

PMID- 24741900
TI  - Fellowship: an investment in your profession.

PMID- 24741899
TI  - How to achieve a good panoramic exposure.

PMID- 24741902
TI  - Staying current with changing technology and information is key to success.

PMID- 24741903
TI  - Traveling the road to education excellence.

PMID- 24741904
TI  - Public health research in Horizon 2020. Results of the work of Independent Expert
      Group of the European Commission.
AB  - The recommendations of Independent Expert Group of European Commission on the
      future public health research priorities for Horizon 2020 funding stream in 2014
      2020 are herewith presented. The group was commissioned in September 2012 by DG
      Research & Innovation of (DG-RTD) of European Commission.

PMID- 24741905
TI  - HBV mutations associated with lamivudine therapy.
AB  - Lamivudine (LMV) is still the most commonly used nucleoside analogue in majority
      of the world. Its administration rapidly leads to resistance associated with
      mutations in HBV polymerase. THE AIM of the study was to assess the prevalence,
      nature and the time of LMV resistant variants appearence during a long term
      therapy. PATIENTS AND METHODS: Study was carried out among 175 chronic hepatitis
      B patients treated with LMV. HBsAg, HBeAg as well as anti-HBe antibodies were
      detected by enzyme immunosorbent assay and HBV-DNA quantification was performed
      by RT-PCR. Mutations in HBV polymerase gen were detected by PCR using specific
      primers and direct sequencing. Liver biopsies were performed in 138 patients to
      evaluate grading and staging of chronic hepatitis by Scheuer's classification.
      RESULTS: Mean pre-treatment viral load was comparable among HBeAg-positive and
      negative patients (4.24 x 10(8) vs. 1.26 x 10(8) IU/ml). Mutations in HBV
      polymerase gen were detected in 96 patients. After 5 years of LMV therapy the
      prevalence of mutations was 51.9% in HBeAg-positive and 56.1% in HBeAg-negative.
      The most common mutations were observed at position 180, followed by 204, 202,
      and 169 of HBV polymerase gen. After average treatment period of 25 months in
      HBeAg-positive and 35 months in HBeAg-negative additional mutation 204 was
      observed in 81% and 77% respectively. CONCLUSIONS: Large majority of patients
      develop point mutations at positions 180 and 204 of HBV polymerase gene after 2
      years of treatment with LMV. These mutations limit the efficacy of LMV but also
      yield cross-resistance with entecavir.

PMID- 24741906
TI  - Non-interventional study AI463-12 of real-world chronic HBV infection management-
      baseline characteristics and treatment patterns of Polish patients kohort.
AB  - AIM: This longitudinal non-interventional study aims to describe the demographics
      data disease characteristics and clinical management of a cross-sectional CHB
      patient population in Poland treated in regional medical centers. MATERIAL AND
      METHODS: [corrected] Between March 2008 and December 2010 we observed patients
      with HBV related liver disease from 5 medical centers in Poland, both sexes, > 18
      years old. At baseline, we used a case report form to extract data from patient
      charts, comprising: sociodemographic data; disease characteristics, HBeAg/
      antiHBeAg status, genotype HBV; co-morbidities; viral load, liver biopsy and ALT
      levels in previous 12 months; treatment history in previous 12 months; current
      CHB treatment; changes in disease characteristics and CHB management; time from
      diagnosis to the therapy and resource utilization and any reasons for termination
      of follow-up. Written informed consent was obtained from all participants
      RESULTS: The analysis population included 253 patients (94 treated and 159 non
      treated at baseline) mostly male (69.1 vs. 56.6). Patients in treated group
      compared with untreated group were: significantly older (mean 42.6 vs. 37.5 years
      respectively, p < 0.001), observed longer since diagnosis(3.9 vs.2.9 years), with
      higher rate of HBeAg(+)(42.6% vs.5.1%), lower ALT activity, and higher VL HBV DNA
      PCR. Of the 53% of treated patients, the most frequently prescribed anti-HBV
      drugs were: Lamivudine (53%), Entecavir (23.7%), Pegylated IFN-alfa2a (23.7%),
      Adefovir (11.1%). During 24 months of follow-up in treated group 13(36.1%)
      patients underwent a treatment switch to another nucleosi(-ti)de analogue, in one
      (2.8%) patient another analogue was added, and in 25 (69.4%)patients the therapy
      was stopped. The proportion of all patients treated with monotherapy at the end
      of follow-up was 99.4%, unfortunately mostly with Lamivudine-49.3%. SUMMARY: 1.
      Despite the several methodological limitations usually associated with this type
      of observation, the collected data does characterize the demographics of polish
      patients chronically infected with HBV well, provides some insights into the
      determinants of treatment initiation and the clinical management of patients in
      real-word settings. 2. These results indicate that in clinical practice in 5
      medical non-academic centers in Poland, European guidelines regarding the
      qualification to HBV treatment were followed, but there were discrepancies
      between the initial treatment decisions in real-life current clinical practice
      and guideline recommendations

PMID- 24741907
TI  - Preparation of HCV infected patients to the triple therapy with first generation
      protease inhibitors.
AB  - In 2011 the European Medicines Agency approved two new drugs (boceprevir and
      telaprevir) to treat patients with chronic hepatitis C or compensated liver
      cirrhosis infected with genotype 1 HCV. Their usage together with a standard
      therapy, ie. pegylated interferon alfa and ribavirin significantly increased the
      chance of sustained virologic response among both previously unsuccessfully
      treated and naive patients. However, this involves a greater number of side
      effects that poorly monitored can be life threatening. To the known side effects
      of standard therapy joined new, such as dysguasia, anorectal symptoms. Both drugs
      can compromise cardiac complications, especially in predisposed patients.
      Furthermore there is also a greater risk of rash and serious skin reactions. New
      problem is the interaction between drugs and first generation protease inhibitors
      resulting from the inhibition of cytochrome p450, common to many drugs pathway.

PMID- 24741908
TI  - Tuberculous meningitis--a case report.
AB  - In this paper we present a case of a 58 years old male with a rare form of
      extrapulmonary tuberculosis--tuberculous meningitis (TBM). Tuberculous meningitis
      is usually caused by hematogenous spread of Mycobacterium from lungs. The TBM is
      a severe disease with high mortality. The symptoms usually increase gradually and
      in the course of the disease 3 clinical stages (prodromal phase, phase of
      neurological symptoms and phase of paresis) may be differentiated. Cerebrospinal
      fluid examination, chest x-ray and sputum culture are crucial for diagnosis of
      TBM. The proper diagnosis and early causative treatment significantly improve the
      outcome of the disease.

PMID- 24741909
TI  - Prevalence of rickettsioses in Poland in 2006-2012.
AB  - INTRODUCTION: Tick-borne diseases, such as rickettsioses, anaplasmosis, Lyme
      boreliosis and bartonellosis are often difficult to correctly diagnose. All these
      disease are present in Poland. OBJECTIVES: The aim of the study was to estimate a
      prevalence of Rickettsia spp. infections in humans in Poland in 2006 to 2012
      based on the results made in the Laboratory of Rickettsiae, Chlamydiae and
      Spirochetes, NIPH-NIH in Warsaw. MATERIAL AND METHODS: The levels of Rickettsia
      spp. and Anaplasma phagocytophilum IgM and IgG antibodies were determined by
      indirect immunofluorescent assay (IFA). From 2006 to 2012, serum samples derived
      from 180 humans suspected for rickettsioses, including 84 patients suspected for
      the infections with typhus and spotted fever group (SFG) rickettsiae, and 96
      patients suspected for anaplasmosis. RESULTS: Specific serum antibodies to the
      SFG rickettsiae have been detected in 5 persons (2.7%). Granulocytic anaplasmosis
      has been recognized in 9 patients (4.9%). While the reporting and registration of
      rickettsioses are obligatory in Poland less than 50% of detected cases are
      reported. CONCLUSIONS: Presented date indicate that in Poland rickettsioses are
      often unrecognized resulting in their underestimation. If research for
      rickettsiosis are made immediately after infection, antibodies will not be
      detect.

PMID- 24741910
TI  - Characteristics of Bartonella spp. infections in Poland in the years 2009-2012
      identified in the laboratory of National Institute of Public Health--National
      Institute of Hygiene.
AB  - INTRODUCTION: Various Bartonella species, (Gram-negative aerobic bacilli) are
      etiologic agents ofzoonotic diseases called bartonelloses, which manifest with
      different symptoms depending on the bacterial species, reservoir and vector. In
      Poland and Europe, the most common bacterial species of the genus Bartonella is
      Bartonella henselae. MATERIAL AND METHODS: [corrected] Serum samples derived from
      patients with clinical symptoms suggesting Bartonella spp. infection, sent in
      2009-2012 to the Laboratory of Rickettsiae, Chlamydiae and Spirochaetes of
      National Institute of Public Health--National Institute of Hygiene in Warsaw were
      tested. Levels of specific IgM and IgG antibodies to B. henselae and B. quintana
      antigens were detected with indirect immunofluorescence method (IFA). RESULTS:
      Six hundred sixty three serum samples were examined from humans with clinical
      symptoms suggestive bartonellosis, in 2009-2012. Specific antibodies for B.
      henselae were detected in 435 patients (65.6%). IgM antibodies were found in 93
      patients (21.4%) including 11 patients (2.5%) with IgM only. IgG antibodies were
      identified in 424 people (78.6%) of whom 342 had IgG antibodies only. The
      antibodies of both classes were detected in 82 people (18.9%). B. quintana
      infections were not found. The majority of samples for study of bartonellosis
      were submitted in the autumn. In patients with confirmed bartonellosis, the most
      common symptoms of disease were lymphadenopathy (86 people, 13%), fever (13
      patients, 2%) and nodular changes in various organs (13 patients, 2%).
      CONCLUSIONS: Infections caused by Bartonella spp. in Poland should be monitored
      to acquire the information on the frequency and distribution of disease in the
      country and their clinical course.

PMID- 24741911
TI  - Mechanism of Vipera berus venom activity and the principles of antivenom
      administration in treatment.
AB  - In the present paper, the actual knowledge on the composition and toxic
      properties of the European common viper venom was analyzed. The organism response
      to the particular components and the methods of neutralization of venom toxin in
      bitten person were presented. On the basis of literature data, the clinical
      course of envenomation with its classification according to the severity of
      symptoms was characterized. In the paper the situations in which administration
      of antivenom is required to neutralize toxic properties of venom and its possible
      adverse reactions were also described.

PMID- 24741912
TI  - "Health 2020"--new framework for health policy. Part II.
AB  - The papers continues presentation of the new framework for health policy related
      to "Health 2020" strategy adopted in September 2012 unanimously by all member
      countries of EURO Region during the 62nd session of the World Health Organization
      Regional Committee for Europe. Four priority areas for action are presented.

PMID- 24741913
TI  - To govern the health or to make the bills of mortality--this is the question for
      public health in Poland.
AB  - In the article important moments in the development of public health at the
      global scale were presented, assuming that postwar evolution proceeded in two
      fundamental phases: the first--events which occurred to the proclamation of the
      Ottawa Charter and introduction of 'new public health' and the second--situations
      reported after Ottawa to the present time. The current challenges for public
      health in Poland were also discussed. It was proposed to differentiate two
      dimensions of public health capacity: internal (ad intra), which is with regard
      to the power centre, condition within the environment and external (ad extra),
      which refers to the relation with surroundings and population and enables to
      deliver sustain services and programmes. The possible strategies aiming at
      increasing ad intra capacity were also indicated.

PMID- 24741914
TI  - Importance of public participation in decision-making process in healthcare
      system illustarted with an example of the development of American and Polish
      scope of health benefit basket.
AB  - The process of the development of health benefit basket may serve as a good
      example of decision-making process in the healthcare system which is based on
      public participation. OBJECTIVE: Comparative analysis of development and
      implementation of health benefit basket in Poland and the USA. MATERIAL AND
      METHODS: On a basis of the literature review, following questions were studied,
      i.e.: What is the origin of health benefit basket development in the USA and
      Poland? What was the role of pubic opinion in determining the range of health
      benefit basket in both countries? What criteria were employed to determine the
      range of health benefit basket in both countries? What conclusions can be drawn
      for Poland from the USA experience of determining the range of health benefit
      basket? RESULTS: Irrespective of the similarities in the origin of health benefit
      basket development, both countries approached this issue differently. In the USA,
      the approach based on social dialogue and patient's perspective was selected
      while in Poland the perspective of public payer predominated. CONCLUSIONS: The
      transparency of principles and social dialogue constitute the fundamental
      elements of effective process of health benefit basket development and
      implementation which is both required and generally unpopular modification.

PMID- 24741915
TI  - Opinions of employees of the National Institute of Public Health--National
      Institute of Hygiene in Warsaw on influenza vaccination.
AB  - INTRODUCTION: Improving influenza vaccination coverage is an important action to
      prevent influenza epidemics and reduce the costs caused by the epidemics.
      Recognising the motives to be vaccinated or failure to vaccinate, especially
      among health care workers, is needed. OBJECTIVES: The aim of presented papers is:
      1) recognising the influenza vaccination coverage among NIPH-NIH employees, 2)
      examining the determinants of decision be vaccinated/not vaccinated, 3)
      estimating the effectiveness of influenza vaccination in relation to sickness
      absence due to respiratory infection. MATERIAL AND METHODS: The study was carried
      out in NIPH-NIH by e-mail questionnaire. Out of 345 employees, 187 (54,2%)
      participated in the study. The questionnaire contained information on influenza
      vaccination and determinants that would potentially affect the decision to
      vaccinate. RESULTS: 18,7% of the participants was vaccinated in the previous
      epidemic season and the half of employees were vaccinated at least one time in
      the previous 10 seasons. Only every fourth family/occupational doctor encouraged
      their patients to vaccinate. The NIPH-NIH employees would be more likely to be
      vaccinated, if the employer has provided free vaccines. The estimation of
      influenza vaccination effectiveness in decreasing the sickness absence due to
      respiratory infection amounted 37%. CONCLUSIONS: Our findings confirmed that
      influenza vaccination contributes to noticeable decreasing of sickness absence.
      Providing free vaccination against influenza by employer could increase
      considerably the coverage.

PMID- 24741916
TI  - The frequency and risk factors of allergy and asthma in children with autism-
      case-control study.
AB  - INTRODUCTION: The evolution of autistic disorders in children depends on many
      factors, like concomitance of the other diseases, which can escalate the autistic
      symptoms. One of those groups are allergic diseases, which have one of the
      highest prevalence rates in children. OBJECTIVES: The aim of this analysis was to
      determine the frequency of asthma and allergy in children with autism in
      comparison to controls and the risk factors of allergic diseases and asthma in
      both groups. MATERIAL AND METHODS: Study population included 96 cases diagnosed
      with childhood or atypical autism and 192 controls matched individually by year
      of birth, gender and physician's practice. The analysis was performed in each
      group separately giving possibility to compare the results between study groups.
      RESULTS: The frequency of asthma and allergic diseases in both groups has not
      revealed any statistically significant differences. Children with autism have
      been affected by asthma in 5,2% and by allergy in 25,0%, controls in 4,7% and
      21,9% respectively. All cases of asthma was diagnosed in boys, commonly allergy
      was also more frequent in boys than girls in both studied groups. However those
      differences was statistically insignificant. The father's allergy and asthma was
      revealed as a risk factor of allergy in children with autism. In controls
      additionally allergy or asthma diagnosed in mother or grandparent increased risk
      of allergy in children. CONCLUSIONS: Children with autism were affected by asthma
      and allergy with similar frequency like children without autistic disorders.
      Allergy in father was the risk factor of allergic diseases in children with
      autism.

PMID- 24741917
TI  - Polish public caries prophylaxis programme for children aged 5, 7 and 15 years,
      implemented in the year 2011.
AB  - BACKGROUND: Continuous monitoring of oral health status improves the quality of
      dental health care and the effectiveness of implemented prevention programs.
      OBJECTIVES: The aim of the study was to assess the caries status in three age
      groups of Polish children and evaluation of the effectiveness of the nationwide
      caries prophylaxis program, including fissure sealing of deciduous and permanent
      teeth. MATERIAL AND METHODS: a group of 6,271 chidren, 5, 7 and 15 years old,
      coming from 16 provinces of Poland, was included in the epidemiological survey.
      The study was based on WHO guidelines (Oral Health Surveys). RESULTS: the
      percentage of children covered by the prophylaxis program in 2011 was as follows:
      5 years old--3.8%, 7 years old--48.3%, 15 years old--7.2%. Five-year-old children
      took part in prophylaxis program in 4 provinces, seven-year-old children--in 10
      provinces, and 15-year-old children--in 3 provinces. The percentage of five-year
      old children with sealed primary and permanent teeth was 0.4% and 0.6%,
      respectively. In the group of seven-year-old children it was 1.7% and 16.4%
      respectively, whereas in the group of 15-year-old children, the percentage of
      sealed permanent teeth was 7.2%. The obtained results varied in different
      provinces of Poland. CONCLUSIONS: Caries prophylaxis program developed for Polish
      children was implemented insufficiently, with significant differences depending
      on sex, age group and regional conditions. The total percentage of children with
      sealed primary and permanent dentition was very low on national scale, regardless
      of age and place of residence.

PMID- 24741918
TI  - Recommendations for thermal disinfection based on the A0 concept according to EN
      ISO 15883.
AB  - The use of aseptic instruments for the care of patients is an essential element
      in the prevention of nosocomial infections. Significant risks have been
      associated with inadequate or improper cleaning and disinfection of reusable
      medical devices. Thermal disinfection with moist heat, based on the A0 concept
      (EN ISO 15883-1), is the most common method for disinfection of medical devices
      in the hospital setting. A0 is a physical parameter denoting the inactivation of
      microorganisms. The concept of A0 is intended to allow equivalent disinfection
      efficiencies to a reference time/temperature to occur at other disinfection
      temperatures. This paper focuses on parametric control of thermal disinfection-
      A0 values as recommended in the standard and their interpretation. The
      experimental fundamentals regarding of an A0 concept are rare. Data on thermal
      disinfection are partly contradictory. The washer disinfectors use thermal
      disinfection programs set in accordance with the parameters: time and
      temperature, which is proven suitable biocidal activity, not based on the A0
      value. Many authorities in the field of disinfection recommends to use higher
      values of A0 than those specified in the standard EN ISO 15883.

PMID- 24741919
TI  - The scope and results of selected epidemiological studies conducted at the
      National Institute of Hygiene in the years 1945-1989.
AB  - The authors present the first article in the series concerning the scope
      ofresearch, scientific, practical, educational and other achievements of the
      National Institute of Hygiene (PZH) since 1945. This article is limited to
      discussing selected studies conducted in the field of epidemiology until the year
      1989. The selection was based on PZH annual reports on the accomplishment of
      planned objectives and the literature positins listed in these reports, as well
      as other documents. The criterion for selection was how the scope of the research
      matched the epidemiological situation within a historical context. The authors
      chose research that yielded practical results which made an impact on the
      epidemiological situation, particularly concerning infectious diseases in Poland.
      The significance of epidemiological research of non-infectious diseases was also
      stressed. In addition, research that was considered by scientists in Poland and
      abroad as contributing to the development of medical methodology was included in
      the selection.

PMID- 24741920
TI  - Efficacy and safety of mitomycin C--augmented revisions of non-functioning
      filtering blebs after trabeculectomy--7 year results.
AB  - PURPOSE: To determine the efficacy and safety of mitomycin C-augmented revision
      in eyes after failed primary trabeculectomy failure. MATERIAL AND METHODS:
      Retrospective review of 40 eyes after a single MMC-augmented revision due to
      primary trabeculectomy failure. MAIN OUTCOME MEASURES: intraocular pressure, best
      corrected visual acuity, number of antiglaucoma medications, complications.
      RESULTS: Twelve months after revision the mean intraocular pressure declined from
      24.5 +/- 6.7 mmHg to 15.4 +/- 4.4 mmHg (p < 0.05) and remained decreased at 24
      months (16.33 +/- 4.2 mmHg) and at 84 months (16.75 +/- 2.8 mmHg). The
      therapeutic success, defined as intraocular pressure < or = 18 mmHg without
      medication at 12 months after revision, was achieved in seventeen eyes (42.5%).
      Fourteen eyes (35.0%) achieved qualified success, defined as intraocular pressure
      < or = 18 mmHg with antiglaucoma medication, and 9 of 40 eyes (22.5%) were
      classified as failures. Mean best corrected visual acuity did not change
      significantly after the surgery (12 month: p = 0.76, 36-48 months: p = 0.25, 72
      84 months: p = 0.15). The mean number of medications was reduced from 1.2 +/- 0.8
      preoperatively to 0.68 +/- 0.8 postoperatively at 12 months, to 0.78 +/- 0.49 at
      24 months and the drop was statistically significantly. Early complications
      developed in 7 (17.5%) eyes but they resolved spontaneously. CONCLUSIONS: MMC
      augmented revision appears to be a safe and useful tool in reducing intraocular
      pressure after trabeculectomy failure. This simple-technique procedure is
      successful in 42.5% of eyes for up to 24-36 months and helps protect the eye from
      other surgical intervention, more destructive for the conjunctiva.

PMID- 24741921
TI  - The reliability and applicability of a macular thickness measurement in the
      diagnostic evaluation of primary open angle glaucoma.
AB  - AIM: The aim of the study was to evaluate the sensitivity and specificity of
      retinal thickness measurements in the macular region and the applicability of
      this method in the diagnosis of primary open-angle glaucoma. MATERIAL AND
      METHODS: A group of 194 subjects (371 eyes) aged 30 to 65 years underwent a
      comprehensive ophthalmic examination including the macular thickness measurement
      using the rerinal thickness, analyzer. The following parameters were determined:
      foveolar average thickness foveal average thickness, perifoveal average thickness
      and posterior pole average thickness. The data was analyzed statistically in
      order to determine the sensitivity, specificity and the likelihood ratio for the
      measurement method. RESULTS: We found the following positive and negative
      likelihood ratio values for the respective interest areas: foveolar average
      thickness (2.374 and 0.456), foveal average thickness (2.501 and 0.482),
      perifoveal average thickness (6.161 and 0.099) and posterior pole average
      thickness (6.019 and 0.124). CONCLUSION: For the perifoveal and posterior pole
      regions, the method of retinal thickness measurement showed a high sensitivity
      and specificity as well as a high positive likelihood ratio and a near-zero
      negative likelihood ratio. The retinal thickness measurements can therefore be
      successfully applied in the diagnosis of primary open-angle glaucoma.

PMID- 24741922
TI  - Conventional pseudophakic monovision--visual function, patient satisfaction and
      complications.
AB  - PURPOSE: To evaluate visual function, patient satisfaction and complications
      after cataract surgery with conventional pseudophakic monovision in a 3-month
      follow-up. METHODS: The following parameters were evaluated in a group of 20
      selected patients (40 eyes) mean age: 62.15 +/- 7.22 years, who underwent
      bilateral cataract surgery with monofocal lens implantation (Alcon SA60AT) in the
      conventional monovision procedure 3 months earlier (target refraction: dominant
      eye-emmetropia, fellow eye--2.0 D): binocular uncorrected visual acuity for near,
      intermediate distance and distance (logMAR), contrast sensitivity (CS-CSV-1000),
      spectacle independence, patient satisfaction (Type Q) and complication rate.
      RESULTS: The mean prescription for distance was in -0.01 +/- 0.14 D in dominant
      eyes, and -1.85 +/- 0.19 D for near in nondominant eyes. Three months after
      surgery, patients had a very good binocular distance, near as well as
      intermediate visual acuities (-0.03 +/- 0.09, -0.1 +/- 0.11, and -0.39 +/- 0.17,
      respectively). Binocular contrast sensitivity values under mesopic and photopic
      conditions for distance and under photopic conditions for near fell in the
      reference range for age. Most patients (80%) did not require any additional
      correction. Spectacle independence for distance, near and intermediate distances
      was 100%, 80% and 90%, respectively. General patient satisfaction was very high
      (9.40/10). There were no postoperative complications. CONCLUSIONS: Cataract
      surgery with monofocal lens implantation during a conventional monovision
      procedure (E,-2.0 D) in a selected group of patients offered a very good
      binocular visual function, a substantial spectacle independence and overall
      patient satisfaction. pseudophakic monovision, visual function, patient
      satisfaction, complications.

PMID- 24741923
TI  - [Familial retinoblastoma in the experience of the Department of Ophthalmology and
      Ocular Oncology in Krakow].
AB  - In this retrospective study we analyzed over 300 patients with diagnosed
      retinoblastoma treated in the Department of Ophthalmology and Ocular Oncology in
      Krakow in 1967-2011. Nine families (parents and offspring) with diagnosed
      familial retinoblastoma present in at least two generations were analyzed. A
      review of the age of onset, diagnosis and recurrence rate of tumors as well as
      the long-term results of applied therapy and advantages of prophylactic
      ophthalmic screening in children at high risk of familial retinoblastoma was
      performed. The results of our observations showed that in offspring the tumors
      were diagnosed earlier, and the therapy outcomes were better as compared to the
      group of Parents. We conclude that these observations were associated with
      performed genetic screening, early prophylactic ophthalmic examination of
      children born in families with diagnosed retinoblastoma and chemoreduction
      treatment.

PMID- 24741924
TI  - [Ultrasound techniques in diagnosis of extrabulbar extension of uveal melanoma].
AB  - PURPOSE: To evaluate the utility of ultrasound examination in detection of
      extraocular extension of uveal melanoma. METHODS: A retrospective study of 170
      enucleated eyes with ciliary body or/and choroidal melanoma and deep intrascleral
      tumor invasion with extrascleral extension. RESULTS: The extrascleral extension
      was detectable before enucleation in 31 eyes (18.24%), and tumor sizes varied
      from 1.5 to 15 mm. Ultrabiomicroscopy used for the anterior tumor assesment,
      shows the routes of extrascleral extension of uveal melanoma. uveal melanoma,
      extraocular extension, ultrasonography.

PMID- 24741925
TI  - [Evaluation of anterior segment lesions in children and adolescents with ocular
      trauma using Visante OCT].
AB  - AIM: To evaluate the anterior eye segment in children and adolescents after
      unilateral ocular trauma, using optical coherence tomography Visante OCT.
      MATERIAL AND METHODS: 19 patients (17 boys and 2 girls), hospitalized in
      Department of Pediatric Ophthalmology due to ocular trauma, were examined. Mean
      age was 12.6 years (6-17 years). 12 patients had blunt ocular trauma, and 7
      patients had a penetrating injury. RESULTS: Hyphaema impeded the view in 5 eyes,
      so Visante OCT was helpful for the right treatment. The anterior chamber
      shallowing was diagnosed in 9 cases, and anterior chamber deepening in 5 cases.
      Lens pathology (subluxation, cataract) was recognized in 4 patients. OCT was
      useful in diagnosis of corneal wound (1 case) and in foreign body removal (1
      case). CONCLUSIONS: Visante OCT provides easy visualization and high-resolution
      documentation. Its ability to image the anterior segment structures despite
      corneal opacification seems particularly important. This technique can be very
      useful in children and adolescents with ocular trauma.

PMID- 24741926
TI  - [Assessment of macular and optic disc morphology in children with unilateral
      hypermmetropic amblyopia].
AB  - PURPOSE: To investigate macular thickness and retinal nerve fiber layer thickness
      of the optic disc using high resolution spectral optical coherence tomography.
      MATERIAL AND METHODS: A study group consisted of 54 eyes of children aged from 5
      to 13 years with unilateral hypermmetropic amblyopia. 25 children aged from 6 to
      14 years with emmetropia or mild hyperopia (SE less than +1.0 D) were recruited
      as a reference group. All patients underwent a comprehensive ocular examination,
      including Scanning Laser Ophthalmoscope/Optical Coherence Tomography scans of the
      macula and the optic disc. The total macular volume, minimal central foveal
      thickness, parafoveal and perifoveal retinal thickness, global retinal nerve
      fiber layer thickness and in 4 quadrants were assessed using Statistica 10.0.
      RESULTS: The total macular volume was significantly higher in amblyopic as
      compared to non-amblyopic eyes--8.9 (8.09-9.27) in the study group, 8.3 (7.17
      9.32) in the reference group respectively. However, the retinal nerve fiber layer
      was significantly thinner in amblyopic eyes. CONCLUSIONS: Amblyopia does not
      affect retinal thickness symmetry between the right and left eye. The analysis of
      Scanning Laser Ophthalmoscope/Optical Coherence Tomography morphometric
      parameters in amblyopic eyes is useful only when compared with the age-matched
      reference group. hypermmetropic amblyopia, macular retinal thickness, retinal
      nerve fiber layer thickness, spectral optical coherence tomography.

PMID- 24741927
TI  - [Blood flow in vessels supplying the eye in persons with degenerative myopia.
      Part I. Blood flow in the ophthalmic artery].
AB  - BACKGROUND: Mechanism of hemodynamic disturbances of blood circulation within the
      afferent vessels supplying the retina and the choroid, considered as one of main
      underlying causes of degenerative changes in myopic patients, is exceptionally
      likely, although not entirely proven. PURPOSE: To estimate the blood flow
      parameters in the ophthalmic artery of myopic subjects, depending on the extent
      and severity of progression of degenerative lesions observed in ocularfundi.
      METHODS: A prospective study included 70 myopic persons, aged from 18 to 79 years
      (44.9 +/- 18.3) with the mean axial ocular length of 27.9 +/- 5.37 mm. According
      to the extent and severity of degenerative lesion progression, patients were
      divided into 4 groups: I - no degenerative changes on the fundus (n = 32; K--23,
      M--9), II--myopic crescent (n = 20; K--14, M--6), III--retinal thinning
      accompanying the myopic crescent (n = 8; K - 6, M - 2), IV--extensive
      chorioretinal atrophy in the fundus (n = 10; K--7, M--3). Using colour Doppler
      ultrasonography (Aplio SSA Toshiba, frequency of the head of 12 MHz) the
      following parameters of the blood flow in the opthalmic artery were determined:
      the maximum (Vmax), minimal (Vmin) and mean (Vm) velocity, resistive index (RI)
      as well as pulsation index (PI). Differences were analysed statistically (the
      variance analysis and the Spearman's rank correlation coefficient). P < 0.05 was
      assumed as statistically significant. RESULTS: In groups I and II blood flow
      parameters were comparable. In group III Vmax, Vmin and Vm were lower than in
      groups I and II. However, an increase in these parameters was shown in group IV.
      The PI remained on the comparable level, and the RI across all the study groups.
      The observed differences were not statistically significant. CONCLUSIONS: The
      severity of degenerative retinal change progression at different stages of myopia
      is related to the blood flow in the ophthalmic artery, although these
      associations are not statistically significant. Blood flow discrepancies between
      the right and left artery, resulting from anatomical asymmetries, does not seem
      to be significant for the development of degenerative changes.

PMID- 24741928
TI  - [Blood flow in vessels supplying the eye in persons with degenerative myopia.
      Part II. Blood flow in the central retinal artery].
AB  - PURPOSE: To analyse the blood flow parameters in the central retinal artery (CRA)
      of myopic patients depending on the severity of the degenerative changes in
      ocular fundi. METHODS: 70 myopic subjects, aged 18 to 79 years, with the axial
      ocular length ranging between 22.61 and 33.36 mm (27.9 +/- 5.37) were examined.
      According to the extent and severity of degenerative lesion progression, patients
      were divided into 4 groups: I--no degenerative changes on the fundus (n = 32; K-
      23, M--9), II--myopic crescent (n = 20; K--14, M--6), III-- retinal thinning
      accompanying the myopic crescent (n = 8; K--6, M--2), IV--extensive chorioretinal
      atrophy in the fundus (n = 10; K--7, M--3). Blood flow parameters in the central
      retinal artery were determined using Doppler Color ultrasonography (Aplio SSA,
      Toshiba), with the 12 MHz probe. The following, standard parameters were
      analysed: maximum (Vmax), minimum (Vmin) and mean (Vm) velocity at systole,
      resistive index (RI) and pulsation index (PI). The differences were analysed
      statistically using the variance analysis and the Spearman's rank correlation
      coefficient, with the p < 0.05 assumed as statistically significant. RESULTS: The
      severity of degenerative retinal changes correlated with the blood flow in CRA.
      At lowered Vmax, Vmin, Vm acompanying the elevated RI and Pi the lesions
      progressed rapidly and were considerably more advanced and extensive.
      CONCLUSIONS: The extent and severity of degenerative processes within the myopic
      retina are directly proportional to blood flow deterioration in the central
      retinal artery. This association can explain the development and progression of
      myopic retinopathy.

PMID- 24741929
TI  - [Surgical management of congenital eyelid ptosis with silicone rod--outcome
      analysis].
AB  - PURPOSE: To analyze the outcomes of surgical management of congenital eyelid
      ptosis with the use of silicone rod. MATERIAL AND METHODS: Congenital eyelid
      ptosis was diagnosed in 12 children aged 2-18 years: 6 cases with unilateral, and
      6 with bilateral ptosis. Analyzing the patients we focused on the function of
      levator muscle before and after the surgery in particular. Ptosis repair was
      performed with the use of silicone rod in all children. RESULTS: Functional and
      cosmetic outcomes of the procedure with the silicone rod were good.

PMID- 24741930
TI  - Unilateral extrafoveal choroidal . ......... eovascularization in a 13-year-old
      child with bilateral optic nerve drusen.
AB  - AIM: The aim of our research was to describe the effect of an off-label
      intravitreal ranibizumab injection for treatment of unilateral extrafoveal
      choroidal neovascularization a with bilateral optic nerve drusen. MATERIAL AND
      METHODS: 13-year-old girl presented with decreased visual acuity of her left eye
      and optic nerve drusen confirmed by B-scan ultrasound examination in both eyes.
      Fluorescein angiography and optical coherence tomography revealed the presence of
      choroidal neovascularization in the left eye. The patient was treated with a
      single injection of ranibizumab and monitored by clinical examination, optical
      coherence tomography and fluorescein angiography. RESULTS: Choroidal
      neovascularization was successfully treated and the best corrected visual acuity
      (Snellen) fully recovered from 20/50 to 20/20 over a period of 2 months. After
      this time at the 30 months follow-up, visual acuity and fundus were stable
      without the recurrence of choroidal neovascularization. CONCLUSIONS: Optic nerve
      drusen should be taken into account and carefully observed as a possible cause of
      peripapillary choroidal neovascularization in children. Ranibizumab can be a
      successful off-label treatment in children suffering from choroidal
      neovascularization associated with optic nerve drusen.

PMID- 24741931
TI  - [Primary intraocular lymphoma--2.5 year follow-up].
AB  - PURPOSE: To present clinical manifestation, diagnosis and treatment of a patient
      with the primary intraocular lymphoma at 2.5 year follow-up. PATIENT AND METHODS:
      Phaco-PPV with silicone oil tamponade was performed in a 62 year old man with a
      diagnosis of recurrent bilateral uveitis of unknown etiology complicated by
      cataract. The creamy-yellow infiltrates were identified and aspirates were
      collected for immunocytochemical evaluation during the surgery--B-cell lymphoma
      was diagnosed. The results of additional tests--hematologic workup, head and
      orbit neuro-imaging--were within normal limits. The patient has been treated with
      regular intraocular injections of Methotrexate at a dose of 400 microg/0.1 ml to
      both eyes for 2.5 years. Regular routine ophtalmic examinations were performed
      during the said follow-up period. RESULTS: The lymphocyte infiltrations in both
      eyes regressed during therapy. The best corrected distance VA remained stable and
      was 0.2 in RE and 0.3 in LE (Snellen). The intraocular pressures and anterior
      segments in both eyes were normal. The new small lymphocyte infiltrates were
      observed in the fundi and were successfully treated with additional Methotrexate
      injections. Methotrexate treatment was augmented with a single laser
      endophotocoagulation in the LE and 2, 3-time argon laser photocagulation in both
      eyes. To date, there no systemic symptoms of the disease have been observed.
      CONCLUSIONS: Local chemotherapy with Methotrexate may be an effective and safe
      treatment of primary intraocular lymphoma. However, due to high potential for
      systemic and local spread, patients should be monitored on a regular basis by
      ophthalmologists and oncologists.

PMID- 24741932
TI  - [Leber's hereditary optic neuropathy--two case reports].
AB  - AIM: The aim of the article is to present 2 cases of LHON revealed in cousins
      (patients' mothers were sisters). MATERIAL AND METHODS: They were both diagnosed
      in the Molecular Medicine Faculty and Department of Ophthalmology, Medical
      University of Wroclaw. RESULTS: Three of the most popular mutations
      characteristic for Leber's hereditary optic neuropathy were negative in both
      patients. CONCLUSION: The patients might have some rare, wild or unidentified
      mutations. Leber's hereditary optic neuropathy, mtDNA, LHON.

PMID- 24741933
TI  - [Microincision cataract surgery--current state of knowledge].
AB  - INTRODUCTION: Standard phacoemulsification is currently performed through a self
      sealing, 2.2-2.8 mm incision. In recent years, the microincision
      phacoemulsification has been introduced, which constituted an important step in
      minimizing the surgical incision. PURPOSE: To present current knowledge of
      phacoemulsification through a microincision (C-MICS and B-MICS). CONCLUSIONS:
      Phacoemulsification through a microincision with implantation of latest
      generation intraocular lenses is an important step in the evolution of cataract
      surgery.

PMID- 24741934
TI  - [Treatment of traumatic iris defects].
AB  - INTRODUCTION: Treating traumatic iris defects is still an important therapeutic
      problem. Various therapeutic strategies are possible, depending on the etiology
      of the defect, its size or localization, as well as other coexisting defects of
      ocular structures. PURPOSE: The purpose of this paper was to describe various
      possible traumatic iris defects, as well as different methods of iris defect
      repair. CONCLUSIONS: In acquired iris defects, ophthalmologists have a relatively
      wide choice of treatments. Each method is safe and effective; however, it is
      important to be aware of their limitations. An appropriate choice of treatment
      strategy for a specific type of iris defect in view of other coexisting ocular
      defects is crucial.

PMID- 24741935
TI  - [Theodor Karol Ballaban (1866-1946)--an ophthalmologist and a brigadier general
      of the Polish Army].
AB  - Theodor Ballaban was born in 1866 and died in 1941. He was distinguished Polish
      ophthalmologist, a brigadier general with a degree of doctor of medical sciences
      obtained in Lviv, a social worker and the author of many works on ophthalmology.
      His son--Karol, who was an ophthalmologist, too, was murdered in Katyn in 1940.
      Theodor Ballaban described a medical case of central retinal vein occlusion,
      emphasizing that lack of spontaneous venous pulsation is a core sign of
      occlusion. Subsequent research confirmed this fact. The subjects of his other
      works were neuro-ophthalmology, ocular anatomy and ocular disease treatment
      methods.

PMID- 24741936
TI  - [Oncolytic properties of some orthopoxviruses, adenoviruses and parvoviruses in
      human glioma cells].
AB  - Currently one of the most promising approaches in development of cancer
      virotherapy is based on the ability of oncolytic viruses to selective infection
      and lysis of tumor cells. AIM: The goal of the study was to identify and evaluate
      perspective oncolytic viruses capable of selectively destroying human glioma
      cells. PATIENTS AND METHODS: Original GB2m, GA14m and GB22m glioma cell cultures
      derived from patients were used for evaluating in vitro oncolytic activity of
      some typical orthopoxviruses, adenoviruses and parvoviruses. RESULTS: The
      oncolytic activity in the human glioma cell models was confirmed for LIVP and WR
      strains of vaccinia virus, Adel2 and Ad2del strains with deletions within E1B/55K
      gene and derived from human adenoviruses type 2 and 5, respectively. CONCLUSIONS:
      We consider these oncolytic viruses as promising agents for the treatment of
      human malignant glioma.

PMID- 24741937
TI  - [Comparative analysis of vascularization degree of hepatocellular carcinoma and
      focal nodular hyperplasia of the liver according to computed tomography and
      morphological studies].
AB  - OBJECTIVE: A comparative analysis of the degree of vascularization of
      hepatocellular carcinoma (HCC) and focal nodular hyperplasia (FNG) of the liver
      at carrying out multislice computed tomography (MCT) and morphological studies.
      PATIENTS AND METHODS: 34 patients operated on for HCC (19 patients) and FNG of
      liver (15 patients) were survey. Preoperative we were analyzed four phases of CT
      research: native, arterial, venous, delayed. Degree of vascularization of tissue
      were evaluated for immunohistochemical preparations on the relative share of the
      area of blood vessels. RESULTS: In native phase of the MCT-study HCC was detected
      as hypodense or izodensnoe education. Growth of the blood CT density depend on
      the type and extent of tumor histological differentiation of cancer. The highest
      values are set in the fabric of FNG and moderately differentiated HCC. The
      highest levels of venous growth observed in well differentiated HCC. Indicators
      of vascularization by CT have maximum values in the unaffected liver parenchyma,
      and the minimum--in the group of poorly differentiated HCC variant. CONCLUSIONS:
      Use of computed tomography with bolus contrast enhancement allows to study the
      characteristics of blood supply of the liver and focal formations. Frequently
      only the use of this method helps to evaluate specific morphological structure of
      tumors--hepatocellular carcinoma or focal nodular hyperplasia. As an additional
      differential diagnostic feature is recommended to increase the density
      determination of tissue formation in the arterial phase computed tomography
      study. The maximum of vascularization by computed tomography and
      immunohistochemistry (with antibodies CD34) are installed in a tissue of highly
      differentiated hepatocellular carcinoma.

PMID- 24741938
TI  - [Hypoxic preconditioning of stem cells as a new approach to increase the efficacy
      of cell therapy for myocardial infarction].
AB  - During the last decade, stem cell research has developed at an accelerated pace.
      Various types of stem cells have been tested for myocardial infarction therapy.
      Despite the preclinical benefits of cell therapy success in clinical trials
      remains modest. The main obstacles to regeneration of the infarcted heart using
      stem cells are: 1) not every stem cell type can differentiate into
      cardiomyocytes; and 2) low survival rates of transplanted cells, due to the harsh
      environment of the infarcted myocardium. Hypoxic preconditioning (HP) has been
      shown to improve transplantation efficacy of mesenchymal stem cells and cardiac
      progenitor cells in animal models of myocardial infarction. It has also been
      shown that transplantation of preconditioned cells decreases infarct size,
      prevents postinfarction remodeling of the heart, and positively modulates
      development of ischemic cardiomyopathy. Hypoxic preconditioning also prevents
      extensive death of transplanted cells due to necrosis and apoptosis during long
      term hypoxia or oxidative stress. The protective effect of HP is based on three
      main processes: (1) modification of cell phenotypes to help survival during
      hypoxia (enhancement of HIF-1alpha expression, ERK1/2 and Akt activation,
      enhancement of erythropoietin receptor expression and erythropoietin production,
      and an elevation in levels of antiapoptotic proteins Bcl-2 and Bcl-xL); (2)
      upregulation of various secretable factors including the vascular endothelial
      growth factor (VEGF) and hepatocyte growth factor (HGF), and expression of VEGF-2
      and HGF-receptors; (3) enhancement in the formation of CXCR4 and CXCR7 receptors,
      which play an important role in mobilization and homing of stem cells in the
      ischemic region.

PMID- 24741939
TI  - [Current concepts of perinatal ischemic injury in the brain neurovascular unit:
      molecular targets for neuroprotection].
AB  - Perinatal hypoxic-ischemic brain injury is a relevant medical and social problem.
      Among many pathological processes in the neonatal period perinatal hypoxic
      ischemic injury is a major cause of further hemorrhage, necrotic and atrophic
      changes in the brain. This review presents recent data on the basic mechanisms of
      the hypoxic-ischemic brain injury along the concept of neurovascular unit
      (neurons, astrocytes, endothelial cells, pericytes) with the focus on alterations
      in cell-to-cell communication. Pathological changes caused by ischemia-hypoxia
      are considered within two phases of injury (ischemic phase and reperfusion
      phase). The review highlights changes in each individual component of the
      neurovascular unit and their interactions. Molecular targets for pharmacological
      improvement of intercellular communication within neurovascular unit as a
      therapeutic strategy in perinatal brain injury are discussed.

PMID- 24741940
TI  - [Changes of epidermal growth factor level in blood serum, saliva and gastric
      juice in children with duodenal ulcer].
AB  - AIM: The aim of our study is to investigate EGF content in biological mediums in
      children with duodenum ulcer depending on phase of the disease and different
      variants of its course. MATERIALS AND METHODS: The present study was performed in
      Federal State Establishment "Nizhniy Novgorod Research Institute of Children
      Gastroenterology", Nizhniy Novgorod, Russia. 92 children, between the ages of 8
      to 17, with duodenum ulcer were under observation. Endoscopy was performed by
      Pentax endoscope (FG-24V). EGF detection was performed in blood serum, gastric
      juice and saliva by ELISA method with Human EGF Kit, "Invitrogen", USA. RESULTS:
      The peculiarities of EGF level changes in human biological mediums, depending on
      phase of the disease. The highest EGF level was detected with acute peptic ulcer
      in the presence of ulcerous defects. EGF level increasing was marked out in the
      remission phaseas ulcerous defects healing, and it didn't reach normal values in
      gastric juice. EGF content changes in biological mediums were revealed with
      different variants of duodenum ulcer clinical course in children. The lowest EGF
      level was marked out in blood, saliva and gastric juice with unfavorable course
      of the disease (frequent relapses, cicatricial-ulcerous strains formation), which
      can serve as a prognostic factor.

PMID- 24741941
TI  - [Cortisol levels in cord blood with various violations of neonatal adaptation].
AB  - Shifting extra uterine existence is a serious test of maturity of all functional
      systems of the newborn, so in recent years, the more attention is payed for the
      adaptation of the newborn. It is known that the pathological course of pregnancy
      is a violation of the functional state of the adrenal cortex, and prolonged
      exposure of the pathological factor leads to the inhibition of adrenocortical
      function and a decrease of the adaptive capabilities of a newborn. Therefore,
      serum cortisol levels could be a predictor of complications in preterm infants.
      Based on this, it seems appropriate to study changes in the content of serum
      cortisol cord blood prior to the development of various syndromes neonatal
      maladjustment. The clinical and laboratory examination of term infants with
      various disorders of adaptation: regurgitation, pain, hyperexcitability ,
      depression, cardio-respiratory depression, bleeding in the skin, toxic erythema.
      It is shown that the most prominent violations maladjustment processes occur on
      the background of decreased cortisol. Border states, which are formed on the
      background of normal or elevated cortisol, are not accompanied by significant
      impairments of adaptation processes. On the basis of the data was drawn a
      conclusion about the possibility of using changes of cortisol in cord blood as a
      reliable indicator of neonatal adaptation processes, pointing to the possibility
      of the development of pathological conditions.

PMID- 24741942
TI  - [Use of mathematical models infrared spectroscopy serum in the differential
      diagnosis of ulcerative colitis and Crohn's disease in children].
AB  - RELEVANCE OF RESEARCH: Inflammatory bowel diseases are among the most severe
      pathologies in pediatric gastroenterology, often lead to disability. Despite the
      similarity of the clinic, pathogenetic mechanisms, the question of the
      differential diagnosis of ulcerative colitis and Crohn's disease is relevant in
      view of their different prognosis and treatment strategy. In recent years, in
      medical uses infrared spectroscopy of blood serum for the differential diagnosis
      of various inflammatory diseases, benign and malignant tumors. Besides finding
      increasing application of mathematical methods for data processing, the so-called
      mathematical modeling of pathological processes, allowing objectify the survey
      results for a more accurate diagnosis and prognosis of pathological processes.
      OBJECTIVE: improving the differential diagnosis of ulcerative colitis and Crohn's
      disease in children. PATIENTS: 21 children with ulcerative colitis, 56 children
      with Crohn's disease and 34 healthy children. The method of infrared spectroscopy
      of serum and mathematical modeling results through multivariate entropy analysis.
      RESULTS: the obtained spectral characteristics of blood serum in children with
      ulcerative colitis and Crohn's disease and in healthy children, as well as
      "images of diseased in these pathologies". CONCLUSION: The use of this medical
      technology reduced the time of diagnosis, which contributes to the timely choice
      of rational treatment strategies and provides an opportunity to avoid the
      development of complications, worsening of the disease.

PMID- 24741943
TI  - [Technology transfer to the facility for production of medicines].
AB  - Innovation development of pharmaceutical industry is close connected to knowledge
      transfer going to each subsequent life cycle phase of medicinal product. Formal
      regulation of technology and knowledge transfer is essential for achievement high
      quality during production of medicines designed during development phase.
      Conceptual tools, approaches and requirements are considered that are necessary
      for knowledge and technology transfer across all the life cycle phases of
      medicines. They are based on scientific knowledge of medicinal products and take
      into account both international and Russian regulations in the area of
      development, production and distribution of medicines. Importance of taking into
      consideration all aspects related to quality of medicines in all steps of
      technology transfer is shown. An approach is described for technology transfer
      organization for Russian pharmaceutical manufacturers based on international
      guides in this area.

PMID- 24741944
TI  - [Potential sensitivity to metformin of the diabetics suffering and not suffering
      with cancer: a pharmacogenetic study].
AB  - The group (totally 156 postmenopausal women) used for the study of 'standard' (S)
      and 'associated' (A) genetic markers of potential sensitivity to metformin (MF)
      consisted of 37 healthy females, 32--with diabetes (DM) without cancer, 64 cancer
      patients with DM, and 23 cancer patients without DM. No significant difference in
      carrying of S-polymorphisms was found between DM patients without and with
      cancer. In cancer patients without DM most characteristic data regarding
      potential MF-response were detected with polymorphisms of STK11 gene while data
      on OCT1_rs622342 and OCT1_R61C variants showed opposite trends. In regard of A
      markers, the tendency to the more often finding of GC genotype of OLR1_GS01C in
      DM patients carrying 'MF-positive' variant of OCT1_R61C deserves to be
      underlined. In patients with new-onset diabetes who carried S-markers of
      potential response to MF higher insulin resistance (OCT1_R61C and OCT1_rs622342)
      as well as lower estradiolemia (STK11 and C11orf65) were discovered. Thus,
      according to genetic S-criteria of sensitivity to MF, DM patients with and
      without cancer differ in lesser degree than they differ from cancer patients
      without DM. It can not be excluded, that The efficiency of such criteria might be
      increased due to combination with A-markers and certain hormonal-metabolic
      indices.

PMID- 24741945
TI  - [Treatment of patients with purulent wounds by using the original method of
      hydrodynamical drainage].
AB  - In this article the work of the Omsk State Medical Academy's department of
      general surgery is presented. The aim of study was to treat patients with
      purulent and necrotic wounds of soft tissue by using novel hydrodynamical
      drainaige. In this research 92 patients were taken part, who were inpatient
      treatment in the department of purulent surgery City Clinical Hospital No 1 named
      Kabanov A. N. 2010-2013 with purulent and necrotic wounds of soft tissue.
      Clinical, laboratory, cytological, bacteriological monitoring were conducted over
      the of wound process during the treatment. Assessment of the reliability of
      differences between the mean value of clinical indicators was with the
      calculation of the criterion t--Student, the method chi2 and Criterion Mann
      Whitney U. The proposed method of treatment of purulent wound promotes fast the
      removal of necrotic tissue and pus in the first phase of the wound process that
      led to more rapid relief of symptoms of intoxication (fever, leukocytosis and
      common symptoms) at the patients of the basic group. Due to faster removal of
      necrotic tissue, reduction of common symptoms of intoxication at the patients of
      the basic group the transition from degenerative and inflammatory type of
      cystograms to regenerative occurred one or two days before than in the comparison
      group.

PMID- 24741946
TI  - [Individual alpha frequency EEG as neurophysiological endophenotype of affective
      predispositions].
AB  - Individual alpha frequency (IAF) of electroencephalogram (EEG) is regarded as a
      neurophysiological endophenotypic indicator of cognitive activity featuring
      individual propensity to efficient cognitive performance and creativity.
      Considering that cognitive coping style is intrinsic part of emotional
      regulation, defining medical aspects of individual health as well as risks of
      psychosomatic diseases, we intended to assess IAF contribution into mechanisms of
      individual emotional reactivity. PARTICIPANTS AND METHODS: As participants was
      healthy man subjects (n = 62). Three models of laboratory induced emotions were
      used: emotional perception (1); anxious apprehension (awaiting of inescapable
      aversive punishment) (2); experience of discrete emotions of anger and joy (3).
      RESULTS: It was revealed that high IAF individuals exhibit predisposition to
      prevalence of parasympathetic activity in the global circuit of autonomous
      regulation, proactive-like coping with inescapable threat, prevailing
      contribution of the positive emotional stance and better accessibility of recent
      positive memories. By contrast, low IAF subjects manifested predisposition to
      prevalence of sympathetic activity in the global circuit of autonomous
      regulation, maladaptive avoidance-like coping with inescapable threat,
      insufficiency positive emotional arousal mechanisms. CONCLUSIONS: It is suggested
      that IAF creates a "hardware" construct featuring individual emotional space and
      adaptability of coping styles to emotional challenges.

PMID- 24741947
TI  - [Estimation of the functional condition of a fetus of pregnancy in chronic
      pyelonephritis].
AB  - Aim of this study was to investigate the condition of the fetus and feto
      placental system in chronic pyelonephritis by identifying features in the
      fetoplacental blood flow and middle cerebral artery system. PATIENTS AND METHODS:
      We examined 68 pregnant women with chronic pyelonephritis and 50 healthy pregnant
      women as a control group. The study conducted a qualitative assessment of fetus
      and placental blood flow and blood flow in the middle cerebral artery of the
      fetus. The data on the condition of feto-placental blood flow and blood flow in
      the middle cerebral artery in the examined pregnant and control group show a
      higher incidence of elevated systolic and diastolic performance ratio in the
      umbilical artery in patients with chronic pyelonephritis than somatically healthy
      women. RESULTS: Studies have shown that the most accurate and informative
      indicator of violations feto-placental circulation is an increase in the
      umbilical artery whose value (2,9 and above) reflects the high degree of
      suffering of the fetus on a background of chronic pyelonephritis. CONCLUSIONS:
      Diagnostically significant is the indicator of the middle cerebral artery blood
      flow, which reflects the mechanism of enhancement of cerebral circulation in
      chronic hypoxia due to violation of feto-placental circulation in patients with
      renal disease.

PMID- 24741948
TI  - [Genes of antioxidant enzymes].
AB  - Oxidative stress plays an important role in the pathogenesis the most of
      diseases. Important components of protecting cells from oxidative stress are
      antioxidant enzymes. Antioxidant enzymes are characterized by population
      differences in enzyme activity. The purpose of the study to summarize and discuss
      information on genetic polymorphisms of antioxidant enzymes in the most
      pathology. The development plays of the role of oxidative stress.

PMID- 24741949
TI  - [The concept of infectious diseases pathogenesis].
AB  - In this article a concept of infectious disease pathogenesis as consisted with
      clinical symptoms is provided. The course of disease, immediate and long-term
      consequences depend on the mode of entry. If the infection comes via oropharynx,
      airway, gastrointestinal tract or via skin, the immune system provides adequate
      immune response. This leads to typical symptoms, cyclical clinic progression and
      usually to the recovery with the formation of full sterile immunity. In case of
      parenteral way of infection, which includes perinatal way, there is no full mode
      of entry, the disease takes chronic course involving visceral organs because of
      different mechanisms of affinity and new tropic organ involving. For the full
      sanogenesis germ or its mediators should persist in the primary focus of
      infection. It is suggested, that HIV, HCV, hepatitis B virus, tetanus, rabies and
      other infectious diseases with inner organs involvement, as well as all slow
      infections, should be treated as infectious diseases with the parental way of
      infection, proceeding with affinity changings, which lead to the appearance of
      new tropic sites in visceral organs. The theory of the mode of entry, affinity,
      appearance of tropic sites in visceral organs should form the basis of modern
      infectology.

PMID- 24741950
TI  - Dietary supplements containing prohibited substances.
AB  - Dietary supplement use among athletes to enhance performance is proliferating as
      more individuals strive for obtaining that chemical competitive edge. As a result
      the concomitant use of dietary supplements containing performance-enhancing
      substances of those falling in the categories outlined in the current review, can
      also be expected to rise. This despite ever-increasing sophisticated analytical
      methodology techniques being used to assay dietary supplement and urine samples
      in doping laboratories. The reasons for this include that a variety of these
      chemical entities, many of them on the prohibited drug list of the WADA, are
      being produced on commercial scales in factories around the world (ephedrine and
      pseudoephedrine, sibutramine, methylhexaneamine, prohormones, 'classic' anabolic
      steroids, clenbuterol, peptide hormones etc.), aggressive marketing strategies
      are being employed by companies and these supplements can be easily ordered via
      e.g. the internet. It can also be anticipated that there will be an increase in
      the number of supplements containing 'designer' steroids and other 'newer'
      molecules. Chromatographic techniques combined with mass spectrometry leading to
      identification of molecular fragments and productions will assist in determining
      these substances. To prevent accidental doping, information regarding dietary
      supplements must be provided to athletes, coaches and sports doctors at all
      levels of competition. The risks of accidental doping via dietary supplement
      ingestion can be minimized by using 'safe' products listed on databases, e.g.
      such as those available in The Netherlands and Germany.

PMID- 24741951
TI  - Standards of nutrition for athletes in Germany.
AB  - The Deutscher Olympische Sportbund (DOSB) founded recently an advisory board for
      German elite athlete nutrition, the 'Arbeitsgruppe (AG) Ernahrungsberatung an den
      Olympiastutzpunkten'. The 'Performance codex and quality criteria for the food
      supply in facilities of German elite sports' have been established since 1997.
      The biochemical equivalent (ATP) for the energy demand is calculated using the
      DLW (Double Labeled Water)-method on the basis of RMR (Resting Metabolic Rate)
      and BMR (Basic Metabolic Rate) at sport type specific exercises and performances.
      Certain nutraceutical ingredients for dietary supplements can be recommended.
      However, quality criteria for nutrition, cooking and food supply are defined on
      the basis of Health Food and the individual physiological/social-psychological
      status of the athlete. Especially food supplements and instant food have to be
      avoided for young athletes. The German advisory board for elite athlete nutrition
      publishes 'colour lists' for highly recommended (green), acceptable (yellow), and
      less recommended (red) food stuff.

PMID- 24741952
TI  - E.L.I.S. (eburnamenine-like indole structures), extracted from medicinal plants,
      as performance catalysts in sports.
AB  - The main goal of this study is to describe the scientific basis of the beneficial
      effects of E.L.I.S. using, intended to improve motor coordination and muscular
      memory, optimizing the neuronal circuits throughout the entire body, involved in
      learning and doing sports. These effects, combined with the synergic action
      presented by these extracts (E.L.I.S.) when administered together with compounds
      of xanthine structure, also lead to improved blood circulation and glucose
      consumption optimizing the cellular metabolism, the production of
      neurotransmitters and the cognitive capacity and, therefore, the cerebral
      activity is reinforced in general both in the short term and the long-term after
      administering them orally. 285 references of scientific literature relating to
      the E.L.I.S. are submitted on the basis of requests from
      olympics2014@memorysecret.net and olympics.sochi@ memorysecret.net.

PMID- 24741953
TI  - [20-Hydroxyecdysone--plant adaptogen: an anabolic effect, possible use in sports
      nutrition].
AB  - In the review the presentation about plant adaptogens--biologically active
      compounds is given. Its administration can help to achieve non-specific state of
      high resistance. The hypothetical mechanism of action: adaptogens are
      prostressors, reducing excessive increase of stress mediators in the following
      stress exposure. The features of adaptogenic effect of phytoecdysteroids,
      polyhydroxylated sterols, which are analogs of hormones of molting and
      metamorphosis of arthropodas, and are structurally similar to glucocorticoids on
      the example of the most widely studied phytoecdysteroid--20-hydroxyecdysone--are
      described. The results of studies of anabolic action of 20-hydroxyecdysone in
      experiments on laboratory animals and the possible explanation (existing in the
      modern scientific literature) of the mechanism of this phenomenon are discussed.
      Scientific publication testifying on the application of phytoecdysteroids to
      remove chronic fatigue syndrome, reducing nerve and muscle fatigue, improve
      memory and attention processes are presented. The prospects of using the 20
      hydroxyecdysone in the composition of food supplements and specialized products
      for athletes are discussed.

PMID- 24741954
TI  - [Anatomic, physiological and metabolic characteristics of young athletes].
AB  - A rational approach to the organization of the training process, the competitive
      cycle, the recovery processes in the practice of child and youth sport requires
      knowledge of the anatomical and physiological characteristics of the organism in
      these age periods. Exchange of amino acids in children of 6 to 12 years takes
      place very actively providing processes of growth and development. The children
      of preschool and early school age have tendency to hypoglycemia due to the
      imperfection of neurohumoral regulation of the mobilization of glycogen in the
      liver and increased utilization of glucose. Glucose utilization corresponds to
      its level in adults, ranging from 8 to 14 years of age. In children under the age
      of 10 an increased tendency to the formation of ketone bodies and ketosis is
      determined. Cholesterol levels increase rapidly after birth. From the period of
      puberty, girls have higher levels of total cholesterol, cholesterol in low
      density lipoprotein (LDL) and high density lipoproteins (HDL) than boys. At the
      age of 6-12 years basal metabolic rate decreases to 1.3-1.5 kcal/kg/h. The
      muscular system increasingly develops. Functional features of the central nervous
      system is the predominance of excitation. Sympathetic part of the autonomic
      nervous system prevails in heart's activity. The role of the hypothalamic
      pituitary system significantly increases in the structure of the endocrine
      glands. The sensitivity of many endocrine glands to the tropic hormone produced
      in the adenohypophysis increases. At the age of 8-12 years the role of
      epinephrine, norepinephrine and other biogenic amines especially increases.
      Period of puberty at the age of 13-17 years is associated with a significant
      change in the hormonal status of the organism. A pubertal growth spurt takes
      place, which occurs 1-2 years earlier in girls than in boys. As for the skeletal
      system the most pronounced growth of tubular bones of the limbs, spine and
      increase of bone density, muscle mass occurs. Heart rate decreases, while the
      duration of the expulsion phase of blood, cardiac output, respiratory functional
      parameters and red blood cells and hemoglobin concentrations increase. Endurance
      rises, physical activity is more economical than in childhood.

PMID- 24741955
TI  - [Features of organization of nutrition for young athletes].
AB  - Organization of nutrition for young athletes implied a regime, which includes the
      distribution of meals throughout the day, the multiplicity of power an nutrients
      that must be strictly consistent with the mode of the training process. Athletes'
      requirements in energy and nutrients vary considerably depending on the sport
      discipline and the amount of intense of physical activity. In the Institute of
      Nutrition of Russian Academy of Medical Sciences the recommended average daily
      sets of products, which are based on daily energy expenditure of young athletes,
      depending on the duration and intensity of physical activity in diverse kinds
      sports has been developed, these kits provide young athletes the necessary
      nutrients and micronutrients. In precompetitive period athletes must be given
      high physical activity and the diet should be mainly protein and fat-containing,
      with a high level of fiber. The training process should be intense for three
      days, then the athlete is advised to transfer to the carbohydrate-rich diet that
      is combined with a significant reduction in the intensity of trainings--glycogen
      super compensation. During competition period meal should be well digestible and
      low-volume. It must contain proteins of high biological values and carbohydrates
      in the required quantity. During this period the inclusion of new dishes and
      products in the menu for athletes is not desirable. During marathon the main aim
      is to recover the energy, water, mineral resources, and to maintain normal blood
      glucose concentrations. This is achieved in the following ways: carbohydrate
      intake with a relatively small amount of liquid, high product content of vitamins
      and minerals that helps to maintain the water-salt metabolism at the appropriate
      level, taking food in liquid form, in small portions. In the recovery period
      adequate nutrition should achieve the following objectives: to restore the acid
      base and fluid and electrolyte balance, eliminate the effect of metabolic
      products (urea, lactic acid, ammonia, etc) associated with high physical
      activity; restore carbohydrate stores, provide plastic exchange, synthesis
      processes. The article also contains the basic sanitary and epidemiological
      requirements for the catering departments, selection of products and sports
      doctors.

PMID- 24741956
TI  - [Vitamin-antioxidant sufficiency of winter sports athletes].
AB  - The sufficiency of 169 athletes (six disciplines: bullet shooting, biathlon,
      bobsleigh, skeleton, freestyle skiing, snowboarding) with vitamins A, E, C, B2,
      and beta-carotene has been investigated in April-September 2013. All athletes
      (102 juniors, mean age--18.5 +/- 0.3 years, and 67 adult high-performance
      athletes, mean age--26.8 +/- 0.7 years) were sufficiently supplied with vitamin A
      (70.7 +/- 1.7 mcg/dl). Mean blood serum retinol level was 15% higher the upper
      limit of the norm (80 mcg/dl) in biathletes while median reached 90.9 mcg/dl.
      Blood serum level of tocopherols (1.22 +/- 0.03 mg/dl), ascorbic acid (1.06 +/-
      0.03 mg/dl), riboflavin (7.1 +/- 0.4 ng/ml), and beta-carotene (25.1 +/- 1.7
      mcg/dl) was in within normal range, but the incidence of insufficiency of
      vitamins E, C, B2, and carotenoid among athletes varied in the range of 0-25, 0
      17, 15-67 and 42-75%, respectively. 95% of adults and 80% of younger athletes
      were sufficiently provided with vitamin E. Vitamin E level in blood serum of
      juniors involved in skeleton and biathlon was lower by 51 and 72% (p < 0.05),
      than this parameter in adult athletes. Vitamin A, C and B2, and beta-carotene
      blood serum level did not significantly differ in junior and adult athletes.
      Women were better supplied with vitamins C, B2, and beta-carotene: a reduced
      blood serum level of these micronutrients in women was detected 2-3 fold rare (p
      < 0.10) than among men. Blood serum concentration of vitamin C (1.20 +/- 0.05
      mg/dl) and beta-carotene (32.0 +/- 3.9 mcg/dl) in women was greater by 15 and 54%
      (p < 0.05) than in men. In general, the biathletes were better provided with
      vitamins compared with other athletes. The vast majority (80%) were optimally
      provided by all three antioxidants (beta-carotene and vitamins E and C). In other
      sports, the relative quantity of athletes sufficiently supplied with these
      essential nutrients did not exceed 56%. The quota of supplied with all
      antioxidants among bullet shooters (31.1%) and bobsledders (23.5%) was
      significantly (p < 0.05) lower than among biathletes. Reduced serum level of one
      antioxidant (mainly beta-carotene) was most often recorded among persons engaged
      in bullet shooting (67%). The simultaneous lack of all three antioxidants was
      found only in freestylers and bobsledders (about 5%). Decreased level of
      antioxidants in blood serum in 40% of athletes was combined with vitamin B2
      deficiency. The data obtained suggest the necessity to optimize diet vitamin
      content of all athletes, taking into account the age and gender differences.
      Contrary to prevailing stereotypes the optimization must involve not only an
      increase in the consumption of vitamins (vitamins E, B group) and carotenoids,
      but sometimes, conversely, their decline (vitamin A) to a level corresponding to
      the physiological needs. The revealed vitamin B2 deficiency may very likely
      indicate a lack of other B group vitamins. In this connection it is necessary to
      draw attention to the need to eliminate the existing vitamin deficiency, and not
      to focus exclusively on antioxidant vitamins. The most reasonable and at the same
      time a safe way to restore the lack of vitamins in the diet of most athletes is
      consistently including in the diet of athletes vitamin and mineral supplements
      and/or fortified foods, containing a complete set of all or at least most of
      vitamins, and in doses that are not excessive and are adequate to maintain
      optimum vitamin status.

PMID- 24741957
TI  - [Identification of genetic polymorphisms associated with overweight in athletes
      of winter sports].
AB  - The identification of polymorphisms rs9939609 gene FTO, Trp64Arg ADRB3 and gene 
      866G> A UCP2 gene using multiplex allele-specific PCR hybridization-fluorescence
      detection in real time has been carried out in highly skilled athletes under the
      age of 30 years engaged in biathlon (n = 25) and bobsleigh (n = 28). The data on
      the frequency of allele risk of obesity has been obtained. The study of
      polymorphism rs9939609 of the FTO gene in biathletes found that 30% of them are
      carriers of the risk allele of obesity (A). Among the bobsledder the frequency of
      allele A is slightly higher than in European populations and is 55.4%. The study
      of gene polymorphism Trp64Arg ADRB3 shored that the frequency of risk allele of
      obesity 64Arg in biathletes (14%) was slightly higher than in the European
      population and biathletes (5.4%). The results of the identification of
      polymorphism -866G> A gene UCP2 in biathletes and bobsledders, found the
      incidence of obesity risk allele, respectively, 52 and 58.7%.

PMID- 24741958
TI  - [Features of nutritive correction in swimmers during their training in conditions
      of midlands].
AB  - The efficiency of the correction of diet using dietary supplements and special
      foods for athletes has been evaluated in 21 highly qualified swimmers, aged 17 to
      26 years, during training cycle in midlands (altitude 1792 m above sea level). A
      personalized approach, consisting of the timely correction of individual programs
      of biomedical support, especially nutritional correction is directly linked to
      the performance of the functional state of an athlete in the most important
      period of training in midlands. At the end of training gathering the increase in
      AcT, ALT blood plasma activity by 18-42% and the reduction in the activity of
      creatine kinase by 26% in the normal ranges (p < 0.05), as well as increased
      cortisol level by 35% was noted, indicating an adequate voltage of the body
      systems in response to the load presented in conjunction with the use of
      pharmacological correction. Hemoglobin concentration in blood increased by 5.6%
      (p < 0.05). Assessment of body composition showed that by the end of the training
      cycle in midlands there was an increase of active cell mass by 3.5% (p < 0.05).
      Significant (p < 0.05) increase in oxygen consumption (by 7%) along with the
      improvement of swimming in the 200 m in the zone of anaerobic threshold (ANSP)
      (by 5%) at the end of the training cycle demonstrate the effectiveness of the
      training process conditions and effective use of nutritional support.

PMID- 24741959
TI  - [Athletic drinks: body rehydration as a vital aspect].
AB  - 106 students of the Faculty of Physical Education and athletes who train at the
      center of power arts (aged 18 to 30 years) have been investigated. The relation
      between the amount of lost and consumed liquid during physical activity has been
      studied. The amount of fluid lost was determined by the method of measuring the
      body mass of an athlete before and after the workout. The kinds of liquids used
      for eliminating dehydration have been analyzed. It has been revealed that while
      doing some physical activity and sports most of those being tested don't restore
      the lost liquid volume (with an average weight loss of 1,15 kg the amount of
      fluids they drunk was 0.91 l). In the given research the interrelation between
      the body weight and the lost liquid amount, and between the lost liquid amount
      and the kind of sports has not been exposed. Liquid loss of athletes in the
      medium intensive training process during the period of 1.5 h at the ambient
      temperature 21-22 degrees C constituted on average 1.53% of the body weight and
      didn't depend on the kind of sports. Despite the advantages of the athletic
      drinks are evident, the share of their consumption among the athletes in Russia
      is negligibly small. The great majority of respondents, namely 72%, use common or
      mineral water to restore the liquid. Only 6% of those being tested consume
      specialized athletic drinks.

PMID- 24741960
TI  - [Medical and biological basis of the recipe of cultured milk products-containing
      rehydrating beverage for the athletes].
AB  - According to the results of the physic-chemical research the composition of new
      isotonic rehydrating beverage has been presented and its nutritional and energy
      value has been calculated. As opposed to other sport drinks of this kind, a part
      of water in the new product is substituted by whey. From the physic-chemical
      standpoint whey is a complicated dispersed system in which hydrated proteins are
      in the form of colloidal solution, lipids are finely emulsified lipoprotein
      particles, carbohydrate and mineral components are close to the composition in
      the whole milk. Natural milk whey complex of macro- and trace elements
      (phosphorus, calcium, magnesium, iron, iodine, zinc, copper, selenium, etc.),
      most of which are in chelated form, have high biological value and
      bioavailability for humans. The content of vitamins, minerals, essential amino
      acids of whey increases the nutritional value of the beverage. Natural sugar
      syrups--containing of lingonberry, cranberry and rosehip were used to flavor the
      drink. The new beverage osmolarity is in the limits of 280-350 mmole/l, which
      allows classifying it as an isotonic sport drink. Natural ingredients and
      moderate carbohydrate, lipid content, and relatively low energy value enable to
      recommend this beverage to the athletes of any specialization without any
      restrictions.

PMID- 24741961
TI  - [Change of blood antioxidant capacity of experimental animals during nutritional
      correction under oxidative stress].
AB  - The effect of nutritional correction (a diet high in foods with antioxidant
      content) on blood parameters in laboratory animals with metabolic disorders
      associated with oxidative stress has been studied. In experimental models of
      laboratory animals (male rabbits weighing 3.5-4.0 kg, n = 40) with purulent
      septic diseases it has been demonstrated that the use of nutritive correction
      (replacement of 100 g of the cereal mixture through day on a mixture of cabbage
      50 g, carrots 50 g, beet 25 g, apple 25 g, kiwi 10 g and garnet 10 g per 1
      rabbit) is not inferior to its efficiency of glutathione use (2 g per day). The
      use of these antioxidants in laboratory animals significantly reduced the
      phenomenon of oxidative stress on the 5th day: blood antioxidant capacity
      significantly increased by 14.9 and 26.6%, and the area of the flash of luminol
      dependent H2O2-induced chemiluminescence of blood plasma reduced by 44.2 and
      48.6% in the experimental groups receiving respectively nutritive correction and
      glutathione. The low-molecula level of blood antioxidant capacity was restored
      and the balance of the activity of superoxide dismutase (decrease) and catalase
      (increase) was achieved on the 10th day of the experiment. These figures
      significantly (p < 0.05) differed from than in the group of animals receiving no
      antioxidant correction. The latter studied parameters of prooxidant-antioxidant
      system reached values comparable with those in intact animals (n = 10) only on
      the 30th day, confirming the advisability of appointing a complex antioxidant
      therapy.

PMID- 24741962
TI  - [The selective dilatation effects of iptakalim on basilar and pulmonary
      arterioles in high-altitude hypoxic rats].
AB  - OBJECTIVE: To study the selective dilatation effects of iptakalim (Ipt) on
      basilar and pulmonary arterioles, and endothelial cell function of these
      arterioles in hypoxic rats. METHODS: SD male rats were divided into 2
      groups:control and hypoxic group fed in normobaric hypoxic environment (O2 7.8%,
      8 h). Arteriole rings about (204 + 5) pm were isolated and the tension of hypoxic
      arterioles pre-contracted by 6 nmol/L endothelin-1 (ET-1) was observed with wire
      myograph system model (DMT 610 m). The relaxing response of hypoxic arterioles
      induced by different concentration of Ipt were detected and endothelial activity
      was also tested by acetylcholine. RESULTS: 10(5) mol/L acetylcholine (ACh)
      mediated vasodilatation of basilar and pulmonary arterioles was greatly reduced
      in the hypoxic group than those in control group (P < 0.05). Compared with normal
      group, a novel ATP-sensitive potassium channel opener Ipt at the concentration
      ranging from 10(-11) mol/L to 10(3) mol/L, caused stronger dose dependent
      vasodilatation on hypoxic pulmonary arterioles, and there was no significant
      difference between control and hypoxic basilar arterioles. CONCLUSION: The
      endothelial function of basilar and pulmonary arterioles was damaged under
      hypoxic state, and Ipt selectively increased dilatation effects on hypoxic
      pulmonary arterioles, but not on hypoxic basilar arterioles which could improve
      high altitude pulmonary edema pathological state and be the novel drug in the
      treatment of pulmonary hypertension.

PMID- 24741963
TI  - [Conflict processing of the frontal cortex and aging change: event-related
      potentials study].
AB  - OBJECTIVE: To explore the working mechanism and age-related change of the
      conflict processing system of the frontal cortex. METHODS: Fifteen normal elderly
      people and 15 youth were performed a modified Eriksen flanker paradigm, while
      event-related potential (ERPs), which include 32 systerm electroencephalography,
      reaction time and correct rate were recorded. RESULTS: The elderly group showed a
      distinct effect of reaction time and effect of conflict in the respond level
      compared with the youth group. The elderly group had a longer time window of N380
      and same amplitude as the youth group. Low resolution brain electromagnetic
      tomography (LORETA) showed the bilateral temporal lobe and the dorsolateral
      prefrontal cortex (especially right) were activated in the youth group, while the
      left temporal lobe, the left dorsolateral prefrontal cortex and left medial
      frontal gyrus were activated in the elderly group. CONCLUSION: When conflict
      stimuli existed in the response level, old people showed frontal interference
      control hypofunction. N380 reflected the activation of the left dorsolateral
      prefrontal cortex and the left temporal lobe during response selection and
      executive control processing in older people.

PMID- 24741964
TI  - [Effect of autophagy inhibitor chloroquine on the proliferation of PASMCs induced
      by hypoxia].
AB  - OBJECTIVE: To investigate the role of autophagy inhibitor chloroquine (CQ) in the
      proliferation of pulmonary arterial smooth muscle cells (PASMCs) in hypoxia
      conditions. METHODS: The following groups in this study were set up: control
      group, hypoxia group, 50 micromol/L CQ + hypoxia group, 50 micromol/L CQ group.
      The viability of PASMCs in every group was detected by MTT assay. Autophagic
      vacuoles in the cells were observed by MDC staining. Protein expression of
      microtubule associated protein light chain 3 (LC3) was measured by Western blot.
      Migration of PASMCs was detected by wound healing assay. RESULTS: Compared with
      control group, no effect on the viability of PASMCs was observed treated by CQ
      alone. In 1% hypoxia group, cell viability increased significantly compared with
      that in control group. The number of autophagic vacuoles and the rate of cell
      migration and also protein expression of LC3-II were also markedly increased.
      Compared with hypoxia group, addition of CQ increased the number of autophagic
      vacuoles and the levels of LC3-II protein, but decreased the proliferation and
      migration of PASMCs. CONCLUSION: Hypoxia could activates autophagy and
      contributes to proliferation and migration of PASMCs, and autophagy inhibitor CQ
      could decrease the effect of hypoxia on PASMCs through inhibiting autophagy
      process.

PMID- 24741965
TI  - [Changes of Ang II during renal injury induced by cisplatin].

PMID- 24741966
TI  - [The different contraction between rat gastric longitudinal and circular smooth
      muscle induced by extracellular nucleotides].
AB  - OBJECTIVE: To test the different contrctile responses of extracellular
      nucleotides, such as ATP, UTP and nucleotide uridine adenosine tetraphosphate
      (Up4A) in gastric longitudinal muscle (LM) and circular muscle (CM). Examined the
      effect of P2X and P2Y receptor antagonists (in this study, we used IP5I and
      suramin) and cyclooxygenase inhibitor (indomethacin) on Up4A induced contractile
      responses in LM and CM. METHODS: The rats were sacrificed and the stomachs were
      opened to gain LM and CM. Using organ bath system to assess contrctile responses
      of smooth muscle. RESULTS: Up4A could induce contractile responses in both CM and
      LM, which were similar with ATP and UTP. IP5 did not attenuate Up4A could induce
      contractions in both LM and CM, but suramin and indomethacin significantly
      inhibited Up4A contraction in CM, but not in LM. CONCLUSION: Our results suggest
      that extracellular nucleosides and their inhibitors induce different responses
      between LM and CM.

PMID- 24741967
TI  - [The deacclimatization symptom scores of 159 youth returning to the same plain
      from different plateau].
AB  - OBJECTIVE: To analysis deacclimatization symptom scores of 159 youth from
      Karakoram and Tibet Ali area, and provide the basis for the development of
      relevant prevention and control measures. METHODS: Using the method of
      epidemiological symptoms questionnaire, 18 symptoms of 190 youth who returned to
      the plain area from the different plateau were investigated. The symptom scores
      of different altitude, age, the time of staying, different units, continuous or
      intermittent stage and education were surveyed. RESULTS: Deacclimatization
      symptom scores among 5,000 meter groups were significantly higher than those of
      4,300 meter and 3,700 meter group (P < 0.05, P < 0.01). There was no significant
      difference between the 4,300 meter group and the 3,700 meter group (P > 0.05).
      There were significant differences among the stayed personnel (different age,
      position, unit, education, time, continuous or intermittent) (P < 0.01). There
      was significant difference between the continuous defended the group and
      intermittent group (P < 0.01). CONCLUSION: Deacclimatization symptom scores were
      related to the plateau exposure time, altitude, workload, plateau continued
      exposure. The older, the longer exposure, the higher altitude, the greater
      workload at plateau were showed higher deacclimatization symptom score.

PMID- 24741968
TI  - [Changes of PKC in rat lung exposed to 2.3 ATA hyperbaric oxygen in different
      times].

PMID- 24741969
TI  - [Effects of E23K polymorphism in KCNJ11 gene on membrane current].
AB  - OBJECTIVE: E23K polymorphism in KCNJ11 gene is associated with cardiovascular
      disease and diabetes. In order to explore the mechanism of E23K correlation to
      related diseases, the effect of E23K polymorphism in KCNJ11 gene on membrane
      current was investigated. METHODS: The exon of KCNJ11 was obtained by PCR
      amplification and the G-->A mutation was completed by overlap extension PCR. The
      sequences of KCNJ11 exon contained 23E or 23K was inserted into pcDNA3.1/CT-GFP
      vector respectively. The recombinant plasmid, pcDNA3.1-KCNJ11(E) and pcDNA3.1
      KCNJ11(K), were transfected into HEK293T cells by lipofectamine and the membrane
      current density was determined by whole-cell patch clamp technique. RESULTS:
      1,173 bp sequences of KCNJ11 gene's exon were amplified by PCR and the
      recombinant expression plasmid, pcDNA3.1-KCNJ11(E) and pcDNA3.1-KCNJ11(K), were
      constructed successful. Positive and negative currents were detected in HEK293T
      cells transfected with difference plasmid by whole-cell patch clamp technique.
      Results showed that the reversed voltage was 50mV. The current in HEK293T cells
      with pcDNA3.1-KCNJ11(E) was significantly greater than that with pcDNA3.1
      KCNJ11(K) (P < 0.05, n = 10). CONCLUSION: The polymorphism of E23K in exon of
      KCNJ11 gene changed the membrane currents in HEK293T cells. It could be an
      experiment support for the possible mechanism between the locus and related
      diseases.

PMID- 24741970
TI  - [Improved methods for monitoring sleep state and respiratory rhythm in freely
      moving rats].
AB  - OBJECTIVE: To improve the method for monitoring sleep state and respiratory
      rhythm of SD rats, providing a solution for rats' chewing on the wires, signal
      loss and instability problems in the animal model of sleep apnea syndrome (SAS).
      METHODS: We improved monitoring electrodes of both electrocorticogram (ECoG) and
      electromyogram (EMG), signal circuit and animal operation. RESULTS: Operation
      time was shortened and wound exposure time was reduced, which made it easier for
      postoperative recovery. The ECoG and EMG signals were more stable with sharp
      image, and signal circuit lines had better conductivity and material durability,
      achieving continuous monitoring for a long time and high success rate. We could
      precisely distinguish the sleep wake state and the sleep apnea events in rats
      according to these signals. CONCLUSION: The improved method is more reliable and
      practical to test the small animal model of SAS, and is more easily to operate
      and the signals are more stable.

PMID- 24741971
TI  - [Hypoxia change the gene expression of insulin-like growth factors family in rat
      prefrontal cortex].

PMID- 24741972
TI  - [Study on application of amphotericin B in the perforated whole-cell patch clamp
      technique].
AB  - OBJECTIVE: Established with amphotericin B perforated patch-clamp technique, to
      study the electrophysiological properties of calyx synapses. METHODS: In the
      present experiments, we studied the application of perforated patch clamp
      technique on the calyx synapses of mice with Amphotericin B. RESULTS: The use of
      Amphotericin B significantly slowed down the decay of channel currents and the
      optimum concentration was 400 microg/ml. CONCLUSION: The syudy developed a stable
      of perforated patch clamp whole cell recording technique, could be more
      effecitve, more real reaction neurons electrophysiological characteristics of the
      channel current. Our work might provide the basic information to future users
      studying the signal transmission and regulation of auditory system of rodents.

PMID- 24741973
TI  - [Study on dynamic change of serum interleukin-17 and interleukin-10 levels in
      patients with acute cerebral infar].

PMID- 24741974
TI  - [The effect and mechanism of curcumin derivative B06 on the myocardium from type
      2 diabetic rats].
AB  - OBJECTIVE: To investigate the protective effect and mechanism of curcumin
      derivatives B06 on myocardium from type 2 diabetic rats. METHODS: Thirty-five
      male SD rats were randomly divided into 5 groups, normal control group (NC
      group), high fat group (HF group), high fat treatment group (FT group), diabetes
      mellitus group (DM group) and diabetes treatment group (DT group) (n = 7). The
      late four groups were fed with high fat food, after four weeks of high fat
      feeding, the rats from DM group and DT group were injected with low dosage of
      streptozocin intraperitoneally to induce diabetes mellitus, FT group and DT group
      were gavaged with curcumin derivatives B06 at the dosage of 0.2 mg/kg x d. The
      blood glucose and lipid were detected biochemically, blood insulin was assayed by
      ELISA and the insulin resistance index was calculated, the morphology of
      myocardium was observed by light and transmission electron microscopy, the
      protein expression of AMP-activated protein kinase alpha (AMPKalpha) and
      phosphorylated AMP-activated protein kinase alpha (p-AMPKalpha) in myocardium
      were tested by Western blot. RESULTS: The level of blood glucose, lipid, insulin
      and the insulin resistance index were increased in HF group and DM group, but
      they were decreased after the treatment with B06. The expression of AMPKalpha and
      p-AMPKalpha were decreased, but they became increased after the treatment of B06.
      There were increased collagen fibers in interstitium and expansion of
      mitochondria in cytoplasm of myocardium from DM group, but they were ameliorated
      in B06 treatment group. CONCLUSION: It is suggested that B06 may relieve the
      damage of myocardium from type 2 diabetic rats and the increased expression of
      AMPKalpha and p-AMPKalpha may be involved in it.

PMID- 24741975
TI  - [Study on the effect of rhodiolaon the protection against fatigue].

PMID- 24741976
TI  - [The relationship of ECG and pregnancy outcome of older pregnant woman in late
      pregnancy].
AB  - OBJECTIVE: To observe the changes of electrocardiogram (ECG) and pregnancy
      outcome of the late pregnancy women. METHODS: Late pregnancy women were divided
      into two groups by age: over 35 group and under 35 group. The incidence of
      abnormal electrocardiogram was recorded when the patients were subjected to
      routine ECG examination. Then the pregnancy, delivery outcome and if there's low
      birth weight newborn were recorded later. RESULTS: The incidence of abnormal ECG
      in over 35 group was significantly higher than that in under 35 group (P < 0.05).
      And the incidence of ST segment changes, arrhythmia in the group of former was
      higher than that in the group of latter (P < 0.05). Among the different type of
      arrhythmia, the incidence of sinus bradycardia and ventricular premature beat in
      the group of former were higher than those in the group of latter (P < 0.05). But
      the incidence of sinus tachycardia in the former group was obviously lower than
      that in the latter group (P < 0.05). The incidence of pregnancy loss in over 35
      with abnormal ECG group was significantly higher than that in under 35 with
      normal or abnormal ECG groups (P < 0.05). The incidence of premature birth in
      over 35 with abnormal ECG group was significantly higher than that in over 35
      with normal ECG group (P < 0.05). The incidence of low body weight in over 35
      with abnormal ECG group was significantly higher than that in under 35 with
      normal ECG group (P < 0.05). CONCLUSION: The late pregnancy women with the age of
      over 35 are more likely to have ECG abnormalities, such as arrhythmia, myocardial
      ischemia and so on. The older pregnant women with abnormal ECG easily suffer from
      pregnancy losing, premature birth and having a low birth weight baby.

PMID- 24741977
TI  - [Effect of siRNA silencing the role of JNK gene in excessive endoplasmic
      reticulum stress on lung ischemia/reperfusion injury].
AB  - OBJECTIVE: To investigate the effect of siRNA silencing the role of C-Jun N
      terminal Kinase (JNK) gene in excessive endoplasmic reticulum stress on lung
      ischemia/reperfusion injury. METHODS: Mouse model of pulmonary ischemia
      reperfusion injury (PIRI) in situ was established with unilateral lung in vivo.
      Seventy experimental mice were randomly allocated into seven groups (n = 10):
      Sham group (Sham group), ischemia reperfusion group (I/R), PBS+
      Lipofectamine2000TM transfection reagent group (I/R + PBS+ Lipo group), negative
      control group (I/R+ SCR group), JNK-siRNA group (I/R + siRNA(JNK1), siRNA(JNK2),
      siRNA(JNK3)). Mice were euthanized after experimental time out, and left lung
      tissue was extracted. Wet/dry lung weight ratio (W/D) and total lung water
      content (TLW) were tested. Light microscope, alveolar damage quantitative
      evaluation index (IQA) and electron microscope were observed. The expression
      levels of JNK and glucose regulatex protein(GRP78) were detected by RT-PCR and
      Western blot. Apoptosis of lung tissue was determined by TUNEL. RESULTS: Compared
      with Sham group, all indicators above of I/R + PBS + Lipo group and I/R + SCR
      group were significantly increased (P < 0.01), and compared with I/R group, those
      indicators of the three groups all had no notable difference; those indicators
      were not statistically different between I/R + PBS + Lipo group and I/R + SCR
      group, and compared to the three groups, the above indicators in JNK-siRNA group
      were lower (P < 0.05, P < 0.01) except that the expression levels of GRP78 was
      not statistically different. CONCLUSION: I/R induces excessive ERS in lung
      tissue, in which JNK pathway participates in apoptosis, leading to lung tissue
      injury.

PMID- 24741978
TI  - [Effect of aerobic exercise on serum ghrelin, glucose and lipids of rats with
      high fat diet].

PMID- 24741979
TI  - [Effect of Xuebijing injection on TLR4--NF-kappaB--IL-1beta pathway of myocardial
      hypoxia/reoxygenation in rats].
AB  - OBJECTIVE: To investigate the role of Xuebijing injection(XBJI, traditional
      Chinese medicine), in inhibiting TLR4--NF-kappaB--IL-1beta pathway of myocardial
      hypoxia/reoxygenation in rats. METHODS: Thirty six male SD rats (280 +/- 30) g
      were randomly divided into six groups (n = 6): normal group (N group), balanced
      perfusion group (BP group), model group (M group), low dose XBJI group (XBJI(L)
      group), middle dose XBJI group (XBJI(M) group), high dose XBJI group (XBJI(H)
      group). By Langendorff isolated heart perfusion device to establish the model of
      myocardial hypoxia/reoxygenation in rats. ELISA was used to detect the
      concentration of interleukin-1beta (IL-1beta); Western blot was used to detect
      the expression of nuclear factor kappa B p65 (NF-kappaB p65) protein and toll
      like receptor 4 (TLR4) protein; and RT-PCR to determine the expression of NF
      kappaB p65 mRNA and TLR4 mRNA;To observe microstructure changes of
      hypoxia/reoxygenation myocardial by light microscopy. RESULTS: Compared with M
      group, the IL-1beta concentration, NF-kappaB p65 and TLR4 protein,NF-kappaB p65
      and TLR4 mRNA of XBJIL group, XBJI(M) group, XBJI(H) group expression decreased
      in varying degrees,and decreased most obviously all in XBJI(M) group (P < 0.05, P
      < 0.01); Myocardical structural damage was serious in M group, and improved after
      treatment XBJI, the most obvious was the XBJI(M). CONCLUSION: Different dose of
      XBJI can inhibit TLR4--NF-kappaB--IL-1beta signal transduction pathway and reduce
      several inflammatory reaction after myocardial hypoxia/reoxygenation injury, the
      4 ml/100 ml of XBJI is the best.

PMID- 24741980
TI  - [Effects of ischemic postconditioning on pneumocyte apoptosis after lung
      ischemia/reperfusion injury in rats].
AB  - OBJECTIVE: To investigate the effects of ischemic postconditioning (IPostC) on
      pneumocyte apoptosis after lung ischemia/reperfusion injury in rats. METHODS:
      Adult male SD rats were randomly divided into 3 groups based upon the
      intervention (n = 8): control group (C), lung ischemic reperfusion group (LIR),
      LIR+ IPostC group (IPostC). At the end of the experiment, blood specimens drawn
      from the arteria carotis were tested for the content of malondialdehyde (MDA),
      the activity of superoxide dismutase (SOD) and myeloperoxidase (MPO); the
      pneumocyte apoptosis index (AI) was achieved by tennrminal deoxynucleotidyl
      transferase mediated dUTP nick end abeling (TUNEL); the expression of Bcl-2, Bax
      protein in lung tissue was accessed by quantitative immunohistochemistry (MHC)
      and Bcl-2, Bax mRNA by RT-PCR. RESULTS: IPostC could significantly attenuate the
      MDA level, MPO activity and improve SOD activity in blood serum which was
      comparable to I/R and significantly reduced the number of TUNEL-positive cells
      compared with I/R group, expressed as Al (% total nuclei) from (39.0 +/- 3.46) to
      (8.0 +/- 0.88) (P < 0.01). The protein and mRNA expression of Bcl-2 and Bax
      showed that IPO significantly attenuated the ischemia/reperfusion-upregulated
      expression of Bax protein but improved the expression of Bcl-2 that improved the
      Bcl-2/Bax ratio (P < 0.01) . CONCLUSION: IPostC may attenuate pneumocyte
      apoptosis in LIRI by up-regulating expression of Bcl-2/Bax ratio and by
      inhibiting oxidant generation and neutrophils filtration.

PMID- 24741981
TI  - [Incidence and risk factors of the causes of death among elderly hypertensive
      inpatients].
AB  - OBJECTIVE: To retrospectively analyze the causes of death in elderly patients
      with hypertension in a hospital-based population from 1993 to 2012. METHODS:
      During the study period of over 19 years, a total of 2866 cases of death in 25238
      hospitalized hypertensive patients with the age of 60 years or older were
      documented. Age, gender, complications, cause of death and other relevant
      variables were collected. All patients were divided into different subgroups
      according to gender, age or hypertension stage and risk stratification. The
      mortality of elderly hypertensive patients was analyzed using chi-square test.
      RESULTS: (1) Target organ damage (TOD) associated with hypertension was present
      in a substantial proportion of elderly patients. The complications related to
      death were heart disease (45.15%), stroke (34.37%), renal failure (11.88%),
      infective disease (4.58%), and cancer (4.06%). (2) Mortality in male elderly
      hypertension was higher than in women (53.31% vs 46.69%). The percentage of
      deaths from heart disease and stroke were higher in men than those in women
      (heart disease: 46.73% vs 43.35%; stroke: 37.04% vs 31.32%). (3) Age-specific
      constituent ratio of cause of death showed that deaths from stroke were
      significantly lower in very old patients (> or = 90 years) than in patients with
      60-79 years of age (P < 0.01). In addition, deaths from heart disease, renal
      failure and infection disease were significantly lower in patients with more than
      90 years than other patients. Deaths from cancer were highest in patients with 70
      79 years of age (P < 0.01). (4) When compared with patients at stage 1 and 2
      hypertension, subjects at stage 3 were more likely to die from stroke (P < 0.01)
      and renal failure (P < 0.05), while less likely to die from heart disease and
      cancer (P < 0.01). Patients in high and very high risk stratification of
      hypertension, compared with subjects in low and medium risk were likely to die
      from renal failure (P < 0.01) whereas less likely to die from heart disease (P <
      0.05) and stroke (P < 0.01). CONCLUSION: Prevalence of complication and TOD is
      high in elderly hypertensive inpatients, especially in deaths. The male patients
      and 60- 79-year-old patients have a higher percentage of causes of death. The
      stage and risk stratification of hypertension are associated with constituent
      ratios of the causes of death.

PMID- 24741982
TI  - [Experimental research into the preventative effect of curcumin on rat diabetes].

PMID- 24741983
TI  - [Protection effect and mechanism of hemin against ischemia/reperfusion injury in
      rat hearts].
AB  - OBJECTIVE: To investigate whether the cardioprotective effect of hemin against
      ischemia/reperfusion (I/R) injury is through the inhibition of calpain activity,
      and to explore its underlying mechanism. METHODS: Sixty-four SD rats were
      randomly divided into eight groups (n = 8): sham, I/R, MDL+ I/R, MDL, hemin +
      I/R, hemin, and ZnPP + hemin+ I/R, ZnPP. Iangendorff isolated rat heart perfusion
      model was used. The rat hearts were suffered from 40 min of ischemia followed by
      30 min of reperfusion. After that, left ventricular developed pressure (LVDP) was
      recorded. Infarct size and release of lactate dehydrogenase (LDH) were measured.
      Calpain, heme oxygenase (HO), and caspase 3 activities were evaluated. Expression
      of calpastatin protein was detected by Western blot. RESULTS: (1) After suffered
      from ischemia/reperfusion, the calpain activity and caspase 3 activity increased.
      MDL28170, an inhibitor of calpain, prevented ischemia/reperfusion induced
      increases in LDH and infarct size, improved the LVDP recovery. (2) Compared with
      ischema/reperfusion rat hearts, pretreatment of hemin enhanced the HO-1 activity,
      decreased the calpain and caspase 3 activities, declined LDH release and infarct
      size, and improved LVDP recovery. (3) Ischemia/reperfusion reduced the expression
      of calpastatin protein in rat hearts, which was inhibited by hemin pretreatment.
      And HO-1 inhibitor could abolish the cardioprotection of hemin. CONCLUSION:
      Cardioprotective effect of hemin against ischemia/reperfusion injury is through
      the inhibition of calpain activity, the mechanism might be involved in the
      increase in calpastatin protein expression.

PMID- 24741984
TI  - [The effect of niflumic acid in hypoxic hypercapnia pulmonary vasoconstriction].
AB  - OBJECTIVE: To investigate the effect of chloride channel blocker--niflumic acid
      (NFA) on the pathological process of hypoxia hypercapnia-induced pulmonary
      vasoconstriction in rats. METHODS: We used the model of hypoxia hypercapnia
      induced pulmonary vasoconstriction rats, and divided the second, third branch
      pulmonary artery rings randomly into four groups (n = 8): control group (N
      group), hypoxia hypercapnia group (H group), DMSO incubation group (HD group),
      niflumic acid group (NFA group). Under acute hypoxia hypercapnia conditions, we
      observed the effects of the three stages of hypoxia hypercapnia-induced pulmonary
      vasoconstriction (HHPV) incubated by NFA in the second, third brach pulmonary
      artery rings. At the same time, the values of rings' tension changings were
      recorded via the method of hypoxia hypercapnia conditions reactivity. And
      investigated the effect of NFA to HHPV. RESULTS: (1) Under the hypoxia
      hypercapnia condition, we observed a biphasic pulmonary artery contractile (the
      phase I rapid contraction and vasodilation; the phase II sustained contraction)
      response in both the second and the third branch pulmonary artery rings compared
      with the control group (P < 0.05 , P < 0.01); (2) The second and third pulmonary
      artery rings incubated by NFA which phase II persistent vasoconstriction were
      significantly attenuated compared with the H group (P < 0.05 , P < 0.01).
      CONCLUSION: The blocker of the chloride channels attenuates the second and third
      branch pulmonary artery rings constriction in rat, especially the phase II
      persistent vasoconstriction, so then have an antagonistic effect on HHPV.

PMID- 24741985
TI  - [Study on CYP1A2, CYP2C9/10 and CYP2C19 activities in rats to create liver
      cirrhosis by using multi-factor complex].

PMID- 24741986
TI  - [Effect of ischemic postconditioning on the expression of myocardium matrix
      metalloproteinase-2 induced by ischemia/reperfusion in rats].
AB  - OBJECTIVE: To investigate the effect of ischemic postconditioning on the
      expression of rat myocardium matris metalloproteinase-2 (MMP-2) induced by
      ischemia/reperfusion (I/R) and relationship between its expression and
      interstitium and the effect on left ventricular function. METHODS: Twenty-four
      rats were randomly divided into 3 groups (n = 8): sham control (SC) group,
      ischemic/reperfusion (I/R) group and ischemic postconditioning (IPTC) group. The
      left ventricular peak systolic pressure and its derivate (+/- dp/dt) were
      calculated; The amount of myocardium collagenous were determined; The vitality of
      superoxide dismutase (SOD) and content of malondialdehyde (MDA) of plasma were
      detected; The activity of myocardium MMP-2 was measured by Western blot and RT
      PCR. RESULTS: As compared with I/R group, IPTC could lower the expression of MMP
      2, ameliorate left ventricular function and increase the content of myocardium
      collagenous. In the meantime, the vitality of superoxide dismutase (SOD) of
      plasma were greatly enhanced and the content of malondialdehyde (MDA) of plasma
      were reduced in IFC group. CONCLUSION: Protective effect of IPIC on myocardium
      may be due to reduce free radical, lower expression of MMP-2 and protect
      myocardial interstitium. MMPs plays an important role in the myocardial
      protection provided by IPTC.

PMID- 24741987
TI  - [Granulosa cells model transfected by ENO1 overexpression adenovirus vector and
      the effect of ENO1 overexpression on progesterone secretion].
AB  - OBJECTIVE: To construct primary cultured granulosa cells model of Zi Gooses
      tansfected by alpha-enolase (ENO1) overexpression adenovirus vector, and to
      detect the effect of ENO1 overexpression of granulose cells on progesterone
      secretion. METHODS: Granulosa cells were infected with Ad-CMV-ENO1 in gradient
      multiplicity of infection(MOI) levels:100, 250, 350 and 400 pfu/cell. Twenty four
      hours and 48 h after infection, green fluorescent protein (GDP) was respectively
      detected by fluorescence inverted microscopy. The effect of ENO1 overexpression
      of granulose cells on progesterone secretion was detected by the step double
      antibody sandwich enzyme-linked immunosorbent assay (ELISA). RESULTS: The optimal
      infection rate (100%) was achieved when MOI was 800 pfu/cell,48h after infection.
      Real time RT-PCR and Western blot showed that the level of mRNA and protein
      expression ENO1 were increased significantly after infection (P < 0.01); The
      granulosa cells progesterone secretion of Ad-CMV-ENO1 group increased
      signigicantly (P < 0.01). CONCLUSION: ENO1 overexpression could make the primary
      culture follicle granulosa cells in vitro improve progesterone secretion.

PMID- 24741988
TI  - [Effect of high humidity environment on immune function in rats].
AB  - OBJECTIVE: To investigate effects of the variation of immune function in high
      humidity environment in different time, and lay a foundation for further study of
      the related mechanism. METHOD: Thirty SD rats were divided into 3 groups (n =
      10): 20 day group, 40 day group in 90% relative humidity chamber and control
      group in normal relative humidity. Peripheral blood and spleens were collected to
      detect the levels of T lymphocyte subsets by Flow Cytometery. RESULTS: In
      peripheral blood of the 20 day group rats, the CD3+ %, CD4+ %, CD8+ % and
      CD4+/CD8+ were 52.91 +/- 6.27, 37.80 +/- 4.11, 14.85 +/- 3.73 and 2.72 +/- 0.82
      separately. Expect CD3+ %, they all had significant differences (P < 0.05). In
      addition, the data of the 40 day group rats showed no diversity in statistics. In
      spleen, CD8+ % of the 20 day group rats was 6.23 +/- 2.87 with significant
      differences (P < 0.05) and IgG, IgA and IgM did not change a lot in blood serum
      of the high humidity groups except C3 of the 20 days group (P < 0.05).
      CONCLUSION: In high humidity environment, the immune function of the rats
      increased in the initial stage. As time went on, the immune function gradually
      went to normal level through the self adjustment.

PMID- 24741989
TI  - [The effect of emodin on the contraction of isolated jejunum smooth muscle of
      rats].
AB  - OBJECTIVE: To investigate the effect of emodin on the contraction of jejunum
      smooth muscle and its underlying mechanisms. METHODS: Rats were randomly divided
      into 7 groups (n = 6): control group, emodin group (1, 5, 10, 20 micromol/L),
      propranolol (PRO) plus emodin group, glibenclamide (GLI) plus emodin group, NG
      Nitro-L-arginine Methyl Ester (L-NAME) plus emodin group, calcium free control
      group and calcium free emodin group. The rats were sacrificed by cervical
      dislocation and the small intestine was isolated. The jejunum segment specimens
      were mounted on an Organ Bath System with a tension transducer. The effect of
      emodin on contraction of jejunum smooth muscle was measured by BL-420E+
      biological signal processing system and the amplitude (AM), tension (TE) and
      frequency (FR) of contraction were determined. RESULTS: (1) Emodin inhibited the
      tension and amplitude of jejunum smooth muscle contraction in a dose-dependent
      manner (P < 0.05, P < 0.01) while the frequency was not obviously influenced. (2)
      PRO (P < 0.05) or GLI (P < 0.01) partly abolished the inhibitory effect of emodin
      on jejunum smooth muscle. (3) L-NAME had no obvious effect on the inhibitory
      effect of emodin. (4) Emodin attenuated the contraction of jejunum smooth muscle
      induced by calcium chloride application into calcium free K-H solution (P <
      0.01). CONCLUSION: Emodin obviously inhibits the amplitude and tension, while has
      no influence on the frequency of jejunum smooth muscle contraction in rats.
      Activation of beta adrenergic receptor, open of ATP sensitive potassium channels,
      and inhibition of the extracellular calcium influx through calcium channels of
      smooth muscle cell membrane might be involved in the process.

PMID- 24741990
TI  - [4 + 2] cycloaddition reaction to approach diazatwistpentacenes: synthesis,
      structures, physical properties, and self-assembly.
AB  - Three novel diazatwistpentacenes (1,4,6,13-tetraphenyl-7:8,11:12-bisbenzo-2,3
      diazatwistpentacene (1, IUPAC name: 9,11,14,16-tetraphenyl-1,6
      dihydrobenzo[8,9]triphenyleno[2,3-g]phthalazine); 1,4-di(pyridin-2-yl)-6,13
      diphenyl-7:8,11:12-bisbenzo-2,3-diazatwistpentacene (2, IUPAC name: 9,16-diphenyl
      11,14-di(pyridin-2-yl)-1,6-dihydrobenzo[8,9]triphenyleno[2,3-g]phthalazine); and
      1,4-di(thien-2-yl)-6,13-diphenyl-7:8,11:12-bisbenzo-2,3-diazatwistpentacene (3,
      IUPAC name: 9,16-diphenyl-11,14-di(thien-2-yl)-1,6
      dihydrobenzo[8,9]triphenyleno[2,3-g]phthalazine)) have been successfully
      synthesized through [4 + 2] cycloaddition reaction involving in situ arynes as
      dienophiles and substituted 1,2,4,5-tetrazines as dienes. Their structures have
      been determined by single-crystal X-ray diffraction, confirming that all
      compounds have twisted configurations with torsion angles between the pyrene unit
      and the 2,3-diazaanthrance part as high as 21.52 degrees  (for 1), 24.74 degrees 
      (for 2), and 21.14 degrees  (for 3). The optical bandgaps for all compounds
      corroborate the values derived from CV. The calculation done by DFT shows that
      the HOMO-LUMO bandgaps are in good agreement with experimental data.
      Interestingly, the substituted groups (phenyl, pyridyl, thienyl) in the 1,4
      positions did affect their self-assembly and the optical properties of as
      resulted nanostructures. Under the same conditions, compounds 1-3 could self
      assemble into different morphologies such as microrods (for 1), nanoprisms (for
      2), and nanobelts (for 3). Moreover, the UV-vis absorption and emission spectra
      of as-prepared nanostructures were largely red-shifted, indicating J-type
      aggregation for all materials. Surprisingly, both 1 and 2 showed aggregation
      induced emission (AIE) effect, while compound 3 showed aggregation-caused
      quenching (ACQ) effect. Our method to approach novel twisted azaacenes through [4
      + 2] reaction could offer a new tool to develop unusual twisted conjugated
      materials for future optoelectronic applications. 

PMID- 24741992
TI  - Effect of swainsonine in Oxytropis kansuensis on Golgi alpha-mannosidase II
      expression in the brain tissues of Sprague-Dawley rats.
AB  - The purpose of this study was to observe the effects of swainsonine in Oxytropis
      kansuensis on the expression of Golgi alpha-mannosidase II (MAN2A1) in the brain
      tissues of Sprague-Dawley (SD) rats. Twenty-four SD rats were randomly divided
      into four groups (experimental groups I, II, and III and a control group) of six
      animals each. The rats were penned as groups and fed feeds containing either 15%
      (swainsonine content = 0.003%), 30% (swainsonine content = 0.006%), or 45%
      (swainsonine content = 0.009%) O. kansuensis for experimental groups I-III,
      respectively, or complete feed for the control group. One hundred and nineteen
      days after poisoning, all rats showed neurological disorders at different
      degrees, which were considered to be successful establishment of a chronic
      poisoning model of O. kansuensis. Rats were sacrificed, and MAN2A1 expression of
      brain tissues was detected by immunohistochemistry and RT-PCR. The results showed
      that MAN2A1 was either not expressed or lowly expressed in the molecular layer of
      the cerebral cortex and hippocampal layers, but was found to be highly expressed
      in other areas of the brain. MAN2A1 expression decreased in the cerebrum and
      cerebellum in experimental groups when compared to the control group, whereas the
      expression of MAN2A1 mRNA was inhibited in cerebral and cerebellar tissues by O.
      kansuensis. These results indicated that O. kansuensis treatment could reduce the
      expression of MAN2A1 in brain tissues of SD rats. 

PMID- 24741993
TI  - Surfaces of complex intermetallic compounds: insights from density functional
      calculations.
AB  - CONSPECTUS: Complex intermetallic compounds are a class of ordered alloys
      consisting of quasicrystals and other ordered compounds with large unit cells;
      many of them are approximant phases to quasicrystals. Quasicrystals are the
      limiting case where the unit cell becomes infinitely large; approximants are
      series of periodic structures converging to the quasicrystal. While the unique
      properties of quasicrystals have inspired many investigations of their surfaces,
      relatively little attention has been devoted to the surface properties of the
      approximants. In general, complex intermetallic compounds display rather
      irregular, often strongly corrugated surfaces, making the determination of their
      atomic structure a very complex and challenging task. During recent years,
      scanning tunneling microscopy (STM) has been used to study the surfaces of
      several complex intermetallic compounds. If atomic resolution can be achieved,
      STM permits visualization of the local atomistic surface structure. However, the
      interpretation of the STM images is often ambiguous and sometimes even impossible
      without a realistic model of the structure of the surface and the distribution of
      the electronic density above the surface. Here we demonstrate that ab initio
      density functional theory (DFT) can be used to determine the energetics and the
      geometric and electronic structures of the stable surfaces of complex
      intermetallic compounds. Calculations for surfaces with different chemical
      compositions can be performed in the grand canonical ensemble. Simulated cleavage
      experiments permit us to determine the formation of the cleavage planes requiring
      the lowest energy. The investigation of the adsorption of molecular species
      permits a comparison with temperature-programmed thermal desorption experiments.
      Calculated surface electronic densities of state can be compared with the results
      of photoelectron spectroscopy. Simulations of detailed STM images can be directly
      confronted with the experimental results. Detailed results are presented for two
      intermetallic compounds that have recently attracted much attention as active and
      highly selective catalysts for the semihydrogenation of alkynes to alkenes, but
      the identification of the catalytically active surfaces was found to be very
      difficult. The crystal structure of B20-type GaPd can be interpreted as the
      lowest order approximant of icosahedral Al-Pd-Mn quasicrystals. Among the low
      index surfaces, the {100} surface shows 2-fold symmetry and the {210} surface
      pseudo-5-fold symmetry; for both the surface stoichiometry is identical to that
      of the bulk. Because the structure lacks inversion symmetry, the {111} surfaces
      have polar character and permit terminations of widely different chemical
      composition. Results for all three surfaces are presented and compared with the
      available experiments. The crystal structure of orthorhombic Al13Co4 is built by
      pentagonal clusters similar to those found in decagonal Al-Co and Al-Ni-Co
      quasicrystals. A simulated cleavage experiment shows that the constituent
      clusters remain intact upon cleavage, resulting in the formation of a highly
      corrugated (100) surface. The calculated STM images are found to be in very good
      agreement with experiment and permit in addition identification of possible
      surface modifications by the desorption of individual atoms. Pentagonal motifs on
      the {210} surface of GaPd and on the (100) surface of Al13Co4 consisting of
      simple- and transition-metal atoms have been identified as the catalytically
      active centers for the semihydrogenation of acetylene to ethylene.

PMID- 24741991
TI  - Structures of exocyclic R,R- and S,S-N(6),N(6)-(2,3-dihydroxybutan-1,4-diyl)-2'
      deoxyadenosine adducts induced by 1,2,3,4-diepoxybutane.
AB  - 1,3-Butadiene (BD) is an industrial and environmental chemical present in urban
      air and cigarette smoke, and is classified as a human carcinogen. It is oxidized
      by cytochrome P450 to form 1,2,3,4-diepoxybutane (DEB); DEB bis-alkylates the
      N(6) position of adenine in DNA. Two enantiomers of bis-N(6)-dA adducts of DEB
      have been identified: R,R-N(6),N(6)-(2,3-dihydroxybutan-1,4-diyl)-2'
      deoxyadenosine (R,R-DHB-dA), and S,S-N(6),N(6)-(2,3-dihydroxybutan-1,4-diyl)-2'
      deoxyadenosine (S,S-DHB-dA) [ Seneviratne , U. , Antsypovich , S. , Dorr , D. Q.
      , Dissanayake , T. , Kotapati , S. , and Tretyakova , N. ( 2010 ) Chem. Res.
      Toxicol. 23 , 1556 -1567 ]. Herein, the R,R-DHB-dA and S,S-DHB-dA adducts have
      been incorporated into the 5'-d(C(1)G(2)G(3)A(4)C(5)X(6)A(7)G(8)A(9)A(10)G(11))
      3':5'-d(C(12)T(13)T(14)C(15)T(16)T(17)G(18)T(19)C(20)C(21)G(22))-3' duplex [X(6)
      = R,R-DHB-dA (R(6)) or S,S-DHB-dA (S(6))]. The structures of the duplexes were
      determined by molecular dynamics calculations, which were restrained by
      experimental distances obtained from NMR data. Both the R,R- and S,S-DHB-dA
      adducts are positioned in the major groove of DNA. In both instances, the bulky
      3,4-dihydroxypyrrolidine rings are accommodated by an out-of-plane rotation about
      the C6-N(6) bond of the bis-alkylated adenine. In both instances, the
      directionality of the dihydroxypyrrolidine ring is evidenced by the pattern of
      NOEs between the 3,4-dihydroxypyrrolidine protons and DNA. Also in both
      instances, the anti conformation of the glycosyl bond is maintained, which
      combined with the out-of-plane rotation about the C6-N(6) bond, allows the
      complementary thymine, T(17), to remain stacked within the duplex, and form one
      hydrogen bond with the modified base, between the imine nitrogen of the modified
      base and the T(17) N3H imino proton. The loss of the second Watson-Crick hydrogen
      bonding interaction at the lesion sites correlates with the lower thermal
      stabilities of the R,R- and S,S-DHB-dA duplexes, as compared to the corresponding
      unmodified duplex. The reduced base stacking at the adduct sites may also
      contribute to the thermal instability. 

PMID- 24741994
TI  - Ectopic insulin secreting neuroendocrine tumor of kidney with recurrent
      hypoglycemia: a diagnostic dilemma.
AB  - BACKGROUND: Hypoglycemia secondary to ectopic insulin secretion of non-pancreatic
      tumors is rare. CASE PRESENTATION: We describe a middle aged woman with recurrent
      hypoglycemia. On evaluation, she was detected to have hyperinsulinemic
      hypoglycemia and right sided renal mass lesion. 68Ga-Dotanoc and 99mTc-HYNICTOC
      scans confirmed the intrarenal mass to be of neuroendocrine origin. Right
      nephrectomy was done and it turned out to be an insulin secreting neuroendocrine
      tumour. Neuroendocrine nature of this tumour was further confirmed by ultra
      structural examination. Her hypoglycemia did not recur after resection of this
      tumour. CONCLUSION: Few cases of ectopic insulin secretion have been reported
      though some are not proven convincingly. This case addresses all the issues
      raised in previous case reports and proves by clinical, laboratory, functional
      imaging and immunohistochemical analysis that ectopic origin of insulin by non
      pancreatic tumors does occur. To our knowledge, this is the first reported case
      of ectopic insulinoma arising from the kidney.

PMID- 24741995
TI  - EPS8, encoding an actin-binding protein of cochlear hair cell stereocilia, is a
      new causal gene for autosomal recessive profound deafness.
AB  - BACKGROUND: Almost 90% of all cases of congenital, non-syndromic, severe to
      profound inherited deafness display an autosomal recessive mode of transmission
      (DFNB forms). To date, 47 causal DFNB genes have been identified, but many others
      remain to be discovered. We report the study of two siblings born to
      consanguineous Algerian parents and affected by isolated, profound congenital
      deafness. METHOD: Whole-exome sequencing was carried out on these patients after
      a failure to identify mutations in the DFNB genes frequently involved. RESULTS: A
      biallelic nonsense mutation, c.88C > T (p.Gln30*), was identified in EPS8 that
      encodes epidermal growth factor receptor pathway substrate 8, a 822 amino-acid
      protein involved in actin dynamics. This mutation predicts a truncated inactive
      protein or no protein at all. The mutation was also present, in the heterozygous
      state, in one clinically unaffected sibling and in both unaffected parents, and
      was absent from the other two unaffected siblings. It was not found in 120
      Algerian normal hearing control individuals or in the Exome Variant Server
      database. EPS8 is an F-actin capping and bundling protein. Mutant mice lacking
      EPS8 (Eps8-/- mice), which is present in the hair bundle, the sensory antenna of
      the auditory sensory cells that operate the mechano-electrical transduction, are
      also profoundly deaf and have abnormally short hair bundle stereocilia.
      CONCLUSION: This new DFNB form is likely to arise from abnormal hair bundles
      resulting in compromised detection of physiological sound pressures.

PMID- 24741997
TI  - Energetic study of 4(3H)-pyrimidinone: aromaticity of reactions, hydrogen bond
      rules, and support for an anomeric effect.
AB  - 4(3H)-Pyrimidinone is observed in nature in equilibrium with other tautomeric
      forms, mimicking the tautomeric equilibrium in pyrimidine nucleobases. In this
      work, the enthalpy of formation in the gaseous phase of 4(3H)-pyrimidinone was
      derived from the combination of the enthalpy of formation in the crystalline
      phase, obtained by static bomb combustion calorimetry, and the enthalpy of
      sublimation, obtained by Knudsen effusion. The gaseous phase enthalpy of
      formation of 4(3H)-pyrimidinone was interpreted in terms of isodesmic reactions
      that consider the enthalpic effects of hydroxypyridines and pyrimidine. After
      comparison of the experimental and computational results, the same type of
      isodesmic reactions was used to study the substituent effects of the hydroxyl
      functional group of 2-, 4-, and 5-hydroxypyrimidines. The influence of
      aromaticity on the energetics of hydroxypyrimidines was evaluated using the
      variation of nucleus-independent chemical shifts for several reactions. The
      influence of intramolecular hydrogen bonds was investigated using the quantum
      theory of atoms in molecules and the geometric rule of Baker and Hubbard to
      identify hydrogen bonds. The energetic results obtained were also interpreted in
      terms of an in plane anomeric effect in the pyrimidine ring. 

PMID- 24741996
TI  - Aiming to improve the quality of primary mental health care: developing an
      intervention for underserved communities.
AB  - BACKGROUND: The purpose of the study was to improve the quality of primary mental
      healthcare in underserved communities through involvement with the wider primary
      care team members and local community agencies. METHODS: We developed training
      intended for all GP practice staff which included elements of knowledge transfer,
      systems review and active linking. Seven GP Practices in four localities (North
      West England, UK) took part in the training. Qualitative evaluation was conducted
      using thirteen semi-structured interviews and two focus groups in six of the
      participating practices; analysis used principles of Framework Analysis. RESULTS:
      Staff who had engaged with the training programme reported increased awareness,
      recognition and respect for the needs of patients from under-served communities.
      We received reports of changes in style and content of interactions, particularly
      amongst receptionists, and evidence of system change. In addition, the training
      program increased awareness of - and encouraged signposting to - community
      agencies within the practice locality. CONCLUSIONS: This study demonstrates how
      engaging with practices and delivering training in a changing health care system
      might best be attempted. The importance of engaging with community agencies is
      clear, as is the use of the AMP model as a template for further research.

PMID- 24741998
TI  - Targeted delivery of CD40L promotes restricted activation of antigen-presenting
      cells and induction of cancer cell death.
AB  - BACKGROUND: Stimulation of CD40 can augment anti-cancer T cell immune responses
      by triggering effective activation and maturation of antigen-presenting cells
      (APCs). Although CD40 agonists have clinical activity in humans, the associated
      systemic activation of the immune system triggers dose-limiting side-effects.
      METHODS: To increase the tumor selectivity of CD40 agonist-based therapies, we
      developed an approach in which soluble trimeric CD40L (sCD40L) is genetically
      fused to tumor targeting antibody fragments, yielding scFv:CD40L fusion proteins.
      We hypothesized that scFv:CD40L fusion proteins would have reduced CD40 agonist
      activity similar to sCD40L but will be converted to a highly agonistic membrane
      CD40L-like form of CD40L upon anchoring to cell surface exposed antigen via the
      scFv domain. RESULTS: Targeted delivery of CD40L to the carcinoma marker EpCAM on
      carcinoma cells induced dose-dependent paracrine maturation of DCs ~20-fold more
      effective than a non-targeted control scFv:CD40L fusion protein. Similarly,
      targeted delivery of CD40L to the B cell leukemia marker CD20 induced effective
      paracrine maturation of DCs. Of note, the CD20-selective delivery of CD40L also
      triggered loss of cell viability in certain B cell leukemic cell lines as a
      result of CD20-induced apoptosis. CONCLUSIONS: Targeted delivery of CD40L to
      cancer cells is a promising strategy that may help to trigger cancer-localized
      activation of CD40 and can be modified to exert additional anti-cancer activity
      via the targeting domain.

PMID- 24741999
TI  - Outcome measures for palliative oxygen therapy: relevance and practical utility.
AB  - Dyspnea is a common symptom in many advanced malignant and non-malignant diseases
      and often is refractory to the usual therapies. In such circumstances palliative
      care approaches are necessary and among them palliative care oxygen therapy can
      be applied although currently its effectiveness is rather uncertain. Palliative
      oxygen therapy can be given on either continuous basis or on demand. Often the
      continuous palliative oxygen therapy is seen as long-term oxygen therapy although
      their aims are rather different. Palliative oxygen therapy was evaluated in
      populations with mixed underlying diseases, with outcome measures not only the
      most appropriate for the setting and therefore these limitations might have
      influenced the overall perceived therapeutic benefit. Therefore an evaluation of
      this method in subsets defined based on the etiology and pathogenic mechanisms
      and with appropriate outcome measures would help to better define the criteria
      for its indication and would increase its acceptability. 

PMID- 24742000
TI  - Selecting optimal partitioning schemes for phylogenomic datasets.
AB  - BACKGROUND: Partitioning involves estimating independent models of molecular
      evolution for different subsets of sites in a sequence alignment, and has been
      shown to improve phylogenetic inference. Current methods for estimating best-fit
      partitioning schemes, however, are only computationally feasible with datasets of
      fewer than 100 loci. This is a problem because datasets with thousands of loci
      are increasingly common in phylogenetics. METHODS: We develop two novel methods
      for estimating best-fit partitioning schemes on large phylogenomic datasets:
      strict and relaxed hierarchical clustering. These methods use information from
      the underlying data to cluster together similar subsets of sites in an alignment,
      and build on clustering approaches that have been proposed elsewhere. RESULTS: We
      compare the performance of our methods to each other, and to existing methods for
      selecting partitioning schemes. We demonstrate that while strict hierarchical
      clustering has the best computational efficiency on very large datasets, relaxed
      hierarchical clustering provides scalable efficiency and returns dramatically
      better partitioning schemes as assessed by common criteria such as AICc and BIC
      scores. CONCLUSIONS: These two methods provide the best current approaches to
      inferring partitioning schemes for very large datasets. We provide free open
      source implementations of the methods in the PartitionFinder software. We hope
      that the use of these methods will help to improve the inferences made from large
      phylogenomic datasets.

PMID- 24742001
TI  - Validity and intra-rater reliability of an android phone application to measure
      cervical range-of-motion.
AB  - BACKGROUND: Concurrent validity and intra-rater reliability using a customized
      Android phone application to measure cervical-spine range-of-motion (ROM) has not
      been previously validated against a gold-standard three-dimensional motion
      analysis (3DMA) system. FINDINGS: Twenty-one healthy individuals (age:31 +/- 9.1
      years, male:11) participated, with 16 re-examined for intra-rater reliability 1-7
      days later. An Android phone was fixed on a helmet, which was then securely
      fastened on the participant's head. Cervical-spine ROM in flexion, extension,
      lateral flexion and rotation were performed in sitting with concurrent
      measurements obtained from both a 3DMA system and the phone.The phone
      demonstrated moderate to excellent (ICC = 0.53-0.98, Spearman rho = 0.52-0.98)
      concurrent validity for ROM measurements in cervical flexion, extension, lateral
      flexion and rotation. However, cervical rotation demonstrated both proportional
      and fixed bias. Excellent intra-rater reliability was demonstrated for cervical
      flexion, extension and lateral flexion (ICC = 0.82-0.90), but poor for right- and
      left-rotation (ICC = 0.05-0.33) using the phone. Possible reasons for the outcome
      are that flexion, extension and lateral-flexion measurements are detected by
      gravity-dependent accelerometers while rotation measurements are detected by the
      magnetometer which can be adversely affected by surrounding magnetic fields.
      CONCLUSION: The results of this study demonstrate that the tested Android phone
      application is valid and reliable to measure ROM of the cervical-spine in
      flexion, extension and lateral-flexion but not in rotation likely due to magnetic
      interference. The clinical implication of this study is that therapists should be
      mindful of the plane of measurement when using the Android phone to measure ROM
      of the cervical-spine.

PMID- 24742003
TI  - Chiral single-chain magnet: helically stacked [Mn(III)2Cu(II)] triangles.
AB  - The one-dimensional complex [Mn(III)2Cu(II)(MU3-O)(Cl-sao)3(EtOH)2].EtOH (Mn2Cu)
      was obtained by the metal replacement reaction of the trinuclear manganese
      complex (Et3NH)[Mn(III)3(MU3-O)Cl2(Cl-sao)3(MeOH)2(H2O)2] with [Cu(acac)2]. The
      Mn2Cu chain exhibits single-chain-magnet behavior with finite-size effects due to
      its large magnetic anisotropy. 

PMID- 24742002
TI  - Expression of uPAR in tumor-associated stromal cells is associated with
      colorectal cancer patient prognosis: a TMA study.
AB  - BACKGROUND: The receptor for urokinase-type plasminogen activator (uPAR) is
      associated with cancer development and progression. Within the tumor
      microenvironment uPAR is expressed by malignant cells as well as tumor-associated
      stromal cells. However, the contribution of uPAR expression in these stromal
      cells to malignancy and patient survival in colorectal cancer is still unclear.
      This study compares the association of uPAR expression in both colorectal tumor
      associated stromal cells and neoplastic cells with clinico-pathological
      characteristics and patient survival using tissue micro arrays (TMA). METHODS:
      Immunohistochemical staining of uPAR expression was performed on tumor tissue
      from 262 colorectal cancer patients. Kaplan-Meier, log rank, and uni- and
      multivariate Cox's regression analyses were used to calculate associations
      between uPAR expression and patient survival. RESULTS: In the colorectal tumor
      associated stromal microenvironment, uPAR is expressed in macrophages,
      (neoangiogenic) endothelial cells and myofibroblasts. uPAR expression in tumor
      associated stromal cells and neoplastic cells (and both combined) were negatively
      associated with overall survival (OS) and Disease Free Survival (DFS). Uni- and
      multivariate Cox's regression analysis for combined uPAR expression in tumor
      associated stromal and neoplastic cells showed significant and independent
      negative associations with OS and DFS. Only uPAR expression in tumor-associated
      stromal cells showed independent significance in the uni- and multivariate
      analysis for DFS. CONCLUSION: This study demonstrates a significant independent
      negative association between colorectal cancer patient survival and uPAR
      expression in especially tumor-associated stromal cells.

PMID- 24742004
TI  - Influence of the length of target DNA overhang proximal to the array surface on
      discrimination of single-base mismatches on a 25-mer oligonucleotide array.
AB  - BACKGROUND: The performance of probes on an oligonucleotide microarray can be
      characterised in terms of hybridisation signal strength and the ability to
      discriminate sequence mismatches between the probe and the hybridising target
      strand, such as those resulting from SNPs. Various properties of the probe affect
      mismatch discrimination, such as probe length and the position of mismatched
      bases, and the effects of these factors have been well characterised in a variety
      of array formats. RESULTS: A low-density microarray was developed to
      systematically investigate the effect of a probe's position within hybridised
      target PCR products on the tolerance and discrimination of single-nucleotide
      mismatches between the probe and target. In line with previous reports,
      hybridisation signals were attenuated by different degrees depending on the
      identity of the mismatch, the position of the mismatch within the probe, and the
      length of the PCR product. However, the same mismatch caused different degrees of
      attenuation depending on the position of the probe within the hybridising
      product, such that improved mismatch discrimination was observed for PCR products
      where a greater proportion of the total length was proximal to the array surface.
      CONCLUSIONS: These results suggest that the degree of mismatch discrimination can
      be influenced by the choice of PCR primers, providing a means by which array
      performance could be fine-tuned in addition to manipulation of the properties of
      the probes themselves.

PMID- 24742005
TI  - Graphene nanoelectromechanical systems as stochastic-frequency oscillators.
AB  - We measure the quality factor Q of electrically driven few-layer graphene
      drumhead resonators, providing an experimental demonstration that Q ~ 1/T, where
      T is the temperature. We develop a model that includes intermodal coupling and
      tensioned graphene resonators. Because the resonators are atomically thin, out-of
      plane fluctuations are large. As a result, Q is mainly determined by stochastic
      frequency broadening rather than frictional damping, in analogy to nuclear
      magnetic resonance. This model is in good agreement with experiment.
      Additionally, at larger drives the resonance line width is enhanced by nonlinear
      damping, in qualitative agreement with recent theory of damping by radiation of
      in-plane phonons. Parametric amplification produced by periodic thermal expansion
      from the ac drive voltage yields an anomalously large line width at the largest
      drives. Our results contribute toward a general framework for understanding the
      mechanisms of dissipation and spectral line broadening in atomically thin
      membrane resonators. 

PMID- 24742006
TI  - Gender minority social stress in adolescence: disparities in adolescent bullying
      and substance use by gender identity.
AB  - Bullying and substance use represent serious public health issues facing
      adolescents in the United States. Few large-sample national studies have examined
      differences in these indicators by gender identity. The Teen Health and
      Technology Study (N = 5,542) sampled adolescents ages 13 to 18 years old online.
      Weighted multivariable logistic regression models investigated disparities in
      substance use and tested a gender minority social stress hypothesis, comparing
      gender minority youth (i.e., who are transgender/gender nonconforming and have a
      gender different from their sex assigned at birth) and cisgender (i.e., whose
      gender identity or expression matches theirs assigned at birth). Overall, 11.5%
      of youth self-identified as gender minority. Gender minority youth had increased
      odds of past-12-month alcohol use, marijuana use, and nonmarijuana illicit drug
      use. Gender minority youth disproportionately experienced bullying and harassment
      in the past 12 months, and this victimization was associated with increased odds
      of all substance use indicators. Bullying mediated the elevated odds of substance
      use for gender minority youth compared to cisgender adolescents. Findings support
      the use of gender minority stress perspectives in designing early interventions
      aimed at addressing the negative health sequelae of bullying and harassment.

PMID- 24742007
TI  - Symptoms, health behavior and understanding of menopause therapy in women with
      premature menopause.
AB  - OBJECTIVE: To explore symptoms, understanding of menopausal therapies, medication
      use and health-related behavior in women with and without premature menopause.
      METHODS: Cross-sectional, questionnaire-based study involving a community-based
      sample of 77 women in Australia: 23 premenopausal, 25 with premature ovarian
      failure (POF) and 29 with medically induced premature menopause (MIPM). RESULTS:
      The median (interquartile range) age of each group was: premenopausal = 29 (13)
      years, POF = 36 (8.0) years and MIPM = 38 (4.0) years (p < 0.001). The reported
      frequency of menopausal symptoms differed across the groups for difficulty
      sleeping (premenopausal = 26%, POF = 44%, MIPM = 69%, p = 0.01), some depression
      symptoms (premenopausal = 4.4-22%, POF = 20-25%, MIPM = 38-59%, p < 0.05), hot
      flushes (premenopausal = 4.4%, POF = 28%, MIPM = 59%, p < 0.001), sweating at
      night (premenopausal = 4.4%, POF = 20%, MIPM = 52%, p < 0.001) and loss of
      interest in sex (premenopausal = 17%, POF = 52%, MIPM = 54%, p = 0.02). More
      women with premature menopause than premenopausal women reported taking
      prescription medication (premenopausal = 52%, POF = 92%, MIPM = 86%, p = 0.002),
      perceived that hormone therapy (HT) was associated with increased breast cancer
      risk (premenopausal = 43%, POF = 56%, MIPM = 79%, p = 0.03) and that HT prevented
      fractures (premenopausal = 13%, POF = 56%, MIPM = 39%, p = 0.01). Most women
      reported not knowing risks/benefits of bioidentical hormone therapy
      (premenopausal = 86%, POF = 56%, MIPM = 75%, p = 0.06). Regarding health-related
      behavior around prevention and screening, varying rates of bone densitometry
      (premenopausal = 4.4%, POF = 64%, MIPM = 59%, p < 0.001), blood glucose testing
      (premenopausal = 39%, POF = 67%, MIPM = 57%, p = 0.16) and cholesterol testing
      (premenopausal = 22%, POF = 71%, MIPM = 54%, p = 0.003) were reported.
      CONCLUSIONS: Differences in understanding of menopausal therapies and health
      related behavior exist among women with premature menopause of differing etiology
      and premenopausal women. While perceived understanding of HT was greater than
      other therapies, targeted education is needed regarding specific risks/benefits
      of menopausal therapies and regarding preventive health screening after premature
      menopause.

PMID- 24742008
TI  - Goodness-of-Fit Tests and Nonparametric Adaptive Estimation for Spike Train
      Analysis.
AB  - When dealing with classical spike train analysis, the practitioner often performs
      goodness-of-fit tests to test whether the observed process is a Poisson process,
      for instance, or if it obeys another type of probabilistic model (Yana et al. in
      Biophys. J. 46(3):323-330, 1984; Brown et al. in Neural Comput. 14(2):325-346,
      2002; Pouzat and Chaffiol in Technical report,
      http://arxiv.org/abs/arXiv:0909.2785, 2009). In doing so, there is a fundamental
      plug-in step, where the parameters of the supposed underlying model are
      estimated. The aim of this article is to show that plug-in has sometimes very
      undesirable effects. We propose a new method based on subsampling to deal with
      those plug-in issues in the case of the Kolmogorov-Smirnov test of uniformity.
      The method relies on the plug-in of good estimates of the underlying model that
      have to be consistent with a controlled rate of convergence. Some nonparametric
      estimates satisfying those constraints in the Poisson or in the Hawkes framework
      are highlighted. Moreover, they share adaptive properties that are useful from a
      practical point of view. We show the performance of those methods on simulated
      data. We also provide a complete analysis with these tools on single unit
      activity recorded on a monkey during a sensory-motor task.Electronic
      Supplementary MaterialThe online version of this article (doi:10.1186/2190-8567-4
      3) contains supplementary material. 

PMID- 24742011
TI  - Beliefs about meditating among university students, faculty, and staff: a theory
      based salient belief elicitation.
AB  - OBJECTIVE: Stress impacts college students, faculty, and staff alike. Although
      meditation has been found to decrease stress, it is an underutilized strategy.
      This study used the Reasoned Action Approach (RAA) to identify beliefs underlying
      university constituents' decision to meditate. PARTICIPANTS: N=96 students,
      faculty, and staff at a large midwestern university during spring 2012. METHODS:
      A survey measured the RAA global constructs and elicited the beliefs underlying
      intention to meditate. Thematic and frequency analyses and multiple regression
      were performed. RESULTS: Quantitative analyses showed that intention to meditate
      was significantly predicted (R2=.632) by attitude, perceived norm, and perceived
      behavioral control. Qualitative analyses revealed advantages (eg, reduced stress;
      feeling calmer), disadvantages (eg, takes time; will not work), and facilitating
      circumstances (eg, having more time; having quiet space) of meditating.
      CONCLUSIONS: Results of this theory-based research suggest how college health
      professionals can encourage meditation practice through individual,
      interpersonal, and environmental interventions.

PMID- 24742012
TI  - Total laparoscopic versus open radical hysterectomy in stage IA2-IB1 cervical
      cancer: disease recurrence and survival comparison.
AB  - BACKGROUND: Few reports have examined the impact of laparoscopic approach on
      survival outcomes in patients with early-stage (IA2-IB1) cervical cancer (CC). In
      this study we aimed to compare disease recurrence and survival outcomes of total
      laparoscopic radical hysterectomy (TLRH) with those for open radical hysterectomy
      (ORH) and pelvic lymphadenectomy in patients with early-stage CC. PATIENTS AND
      METHODS: A single-center, retrospective analysis was conducted in a total of 68
      patients who treated with TLRH (n=22) or ORH (n=46) between 2007 and 2010. The
      primary endpoint of the study was progression-free survival (PFS). RESULTS:
      Median follow-up time was 42.50 months (range, 38.40-55.42 months) for the TLRH
      group and 43.50 months (range, 37.66-52.65) for the ORH group. The study groups
      were comparable in terms of baseline characteristics except the ORH group had
      more patients with tumor size greater than 2 cm (P=.026), depth of stromal
      invasion greater than 33% (P<.0001), and International Federation of Gynecology
      and Obstetrics stage IB1 disease (P=.019). However, these factors had no impact
      on overall and PFS in Cox regression analyses. In total, three recurrences were
      observed in the TLRH group. Two of the 3 patients were alive with no evidence of
      disease, and the remaining individual was alive with disease (AWD). In the ORH
      group, 5 patients had recurrences. Two of the 5 patients died of disease, and
      three were AWD. The estimated 3-year PFS (86.1% versus 90.6%, respectively;
      P=.32) and overall survival (100% vs. 95.4%, respectively; P=.82) were comparable
      in the TLRH and ORH groups. CONCLUSIONS: TLRH and ORH have similar survival
      outcomes in patients with early-stage CC.

PMID- 24742013
TI  - Efficacy and safety of canagliflozin compared with placebo in older patients with
      type 2 diabetes mellitus: a pooled analysis of clinical studies.
AB  - BACKGROUND: Canagliflozin is a sodium glucose co-transporter 2 inhibitor
      developed for the treatment of patients with type 2 diabetes mellitus (T2DM). The
      efficacy and safety of canagliflozin were evaluated in patients with T2DM <65 and
      >=65 years of age. METHODS: Pooled data from 4 randomised, placebo-controlled, 26
      week, Phase 3 studies (N = 2,313) evaluating canagliflozin 100 and 300 mg were
      analysed by age: <65 years (n = 1,868; mean age, 52.8 years) or >=65 years (n =
      445; mean age, 69.3 years). Efficacy evaluations included change from baseline in
      glycaemic parameters and systolic blood pressure (BP), and percent change from
      baseline in body weight. Assessment of safety/tolerability included adverse event
      (AE) reports, incidence of documented hypoglycaemia, and percent change from
      baseline in fasting plasma lipids. RESULTS: Canagliflozin 100 and 300 mg reduced
      HbA1c and fasting plasma glucose relative to placebo in patients <65 and >=65
      years of age. Both canagliflozin doses reduced body weight and systolic BP
      relative to placebo in patients <65 and >=65 years of age. Incidence of overall
      AEs was similar across all treatment groups in patients <65 and >=65 years of
      age. Incidences of serious AEs and AE-related discontinuations were similar
      across all treatment groups in patients <65 years of age and higher with
      canagliflozin 100 mg than other groups in patients >=65 years of age. As in
      patients <65 years of age, incidences of genital mycotic infections and osmotic
      diuresis-related AEs were higher with canagliflozin relative to placebo in those
      >=65 years of age. Incidences of urinary tract infections (UTIs), renal-related
      AEs, AEs related to volume depletion, and documented hypoglycaemia episodes were
      similar across all treatment groups in patients >=65 years of age; no notable
      trends were observed with canagliflozin 100 and 300 mg relative to placebo in
      these AEs among patients <65 years of age. Changes in lipid parameters with
      canagliflozin were similar in both age subsets. CONCLUSIONS: Canagliflozin
      improved glycaemic control, body weight, and systolic BP, and was generally well
      tolerated in older patients with T2DM. TRIAL REGISTRATION: ClinicalTrials.gov,
      NCT01081834; NCT01106677; NCT01106625; NCT01106690.

PMID- 24742014
TI  - Evaluation of the acute flacid paralysis (AFP) surveillance system in Bikita
      district Masvingo province 2010.
AB  - BACKGROUND: AFP is a rare syndrome and serves as a proxy for poliomyelitis. The
      main objective of AFP surveillance is to detect circulating wild polio virus and
      provide data for developing effective prevention and control strategies as well
      planning and decision making. Bikita district failed to detect a case for the
      past two years. FINDINGS: A total of 31 health workers from 14 health centres
      were interviewed. Health worker knowledge on AFP was low in Bikita. The system
      was acceptable, flexible, and representative but not stable and not sensitive
      since it missed1 AFP case. The system was not useful to the district since data
      collected was not locally used in anyway. The cost of running the system was
      high. The district had no adequate resources to run the system. Reasons for not
      reporting cases was that the mothers were not bringing children with AFP and
      ignorance of health workers on syndromes captured under AFP. CONCLUSION: Health
      worker's knowledge on AFP was low and all interviewed workers needed training
      surveillance. The system was found to be flexible but unacceptable. Reasons for
      failure to detect AFP cases could be, no cases reporting to the centres, lack of
      knowledge on health workers hence failure to recognise symptoms, high staff
      turnover.

PMID- 24742015
TI  - Synergistic effects of colchicine combined with atorvastatin in rats with
      hyperlipidemia.
AB  - BACKGROUND: Inflammation and endothelial dysfunction is implicated in the
      atherosclerosis initiation and progression in the setting of hyperlipidemia.
      Colchicine is a potent anti-inflammatory agent and whether colchicine combined
      with atorvastatin has synergistic effects on inflammation amelioration and
      endothelial function improvement is unknown. METHODS: Hyperlipidemic rat model
      was produced by high-fat and high-cholesterol diet for 6 weeks. Rats with normal
      diet were served as shame group. In hyperlipidemic group, normal saline,
      atorvastatin (10 mg/kg body weight/day), colchicines (0.5 mg/kg body weight/day),
      or atorvastatin combined with colchicines (same dosages) were prescribed for 2
      weeks. Serum levels of lipid profile, C-reactive protein (CRP), liver enzyme,
      lipoprotein associated phospholipase A2 (Lp-PLA2) and nitric oxide (NO)
      production were serially assessed. RESULTS: Before the beginning of the study,
      all laboratory variables were comparable among each group. After 6 weeks of
      hyperlipidemic model production, serum levels of cholesterols, CRP and Lp-PLA2
      were significantly increased when compared to sham group, whereas NO production
      was reduced. With 2 weeks of colchicine therapy, serum levels of CRP and Lp-PLA2
      were decreased and NO production was enhanced in the colchicine group in a lipid
      lowering independent manner. Added colchicine into atorvastatin therapy further
      improved NO production and decreased CRP and Lp-PLA2 levels, indicating a
      potential synergism of colchicine and atorvastatin. CONCLUSION: Colchicine
      combined with atorvastatin may have stronger protective effects on improving
      endothelial function and ameliorating inflammation in rats with hyperlipidemia.

PMID- 24742016
TI  - Phylogeographic pattern of Rhizophora (Rhizophoraceae) reveals the importance of
      both vicariance and long-distance oceanic dispersal to modern mangrove
      distribution.
AB  - BACKGROUND: Mangroves are key components of coastal ecosystems in tropical and
      subtropical regions worldwide. However, the patterns and mechanisms of modern
      distribution of mangroves are still not well understood. Historical vicariance
      and dispersal are two hypothetic biogeographic processes in shaping the patterns
      of present-day species distributions. Here we investigate evolutionary
      biogeography of mangroves in the Indo-West Pacific (IWP) and western Atlantic
      East Pacific (AEP) regions using a large sample of populations of Rhizophora (the
      most representative mangrove genus) and a combination of chloroplast and nuclear
      DNA sequences and genome-wide ISSR markers. RESULTS: Our comparative analyses of
      biogeographic patterns amongst Rhizophora taxa worldwide support the hypothesis
      that ancient dispersals along the Tethys Seaway and subsequent vicariant events
      that divided the IWP and AEP lineages resulted in the major disjunctions. We
      dated the deep split between the Old and New World lineages to early Eocene based
      on fossil calibration and geological and tectonic changes. Our data also provide
      evidence for other vicariant processes within the Indo-West Pacific region in
      separating conspecific lineages of SE Asia and Australia-Pacific at the Oligocene
      Miocene boundary. Close genetic affinities exist between extant Fijian and
      American lineages; East African and Australian lineages; and Australian and
      Pacific lineages; indicating relatively more recent oceanic long-distance
      dispersal events. CONCLUSIONS: Our study demonstrates that neither vicariance nor
      dispersal alone could explain the observed global occurrences of Rhizophora, but
      a combination of vicariant events and oceanic long-distance dispersals can
      account for historical diversification and present-day biogeographic patterns of
      mangroves.

PMID- 24742017
TI  - Germline genes hypomethylation and expression define a molecular signature in
      peripheral blood of ICF patients: implications for diagnosis and etiology.
AB  - BACKGROUND: Immunodeficiency Centromeric Instability and Facial anomalies (ICF)
      is a rare autosomal recessive disease characterized by reduction in serum
      immunoglobulins with severe recurrent infections, facial dysmorphism, and more
      variable symptoms including mental retardation. ICF is directly related to a
      genomic methylation defect that mainly affects juxtacentromeric heterochromatin
      regions of certain chromosomes, leading to chromosomal rearrangements that
      constitute a hallmark of this syndrome upon cytogenetic testing. Mutations in the
      de novo DNA methyltransferase DNMT3B, the protein ZBTB24 of unknown function, or
      loci that remain to be identified, lie at its origin. Despite unifying features,
      common or distinguishing molecular signatures are still missing for this disease.
      METHOD: We used the molecular signature that we identified in a mouse model for
      ICF1 to establish transcriptional biomarkers to facilitate diagnosis and
      understanding of etiology of the disease. We assayed the expression and
      methylation status of a set of genes whose expression is normally restricted to
      germ cells, directly in whole blood samples and epithelial cells of ICF patients.
      RESULTS: We report that DNA hypomethylation and expression of MAEL and SYCE1
      represent robust biomarkers, easily testable directly from uncultured cells to
      diagnose the most prevalent sub-type of the syndrome. In addition, we identified
      the first unifying molecular signatures for ICF patients. Of importance, we
      validated the use of our biomarkers to diagnose a baby born to a family with a
      sick child. Finally, our analysis revealed unsuspected complex molecular
      signatures in two ICF patients suggestive of a novel genetic etiology for the
      disease. CONCLUSIONS: Early diagnosis of ICF syndrome is crucial since early
      immunoglobulin supplementation can improve the course of disease. However, ICF is
      probably underdiagnosed, especially in patients that present with incomplete
      phenotype or born to families with no affected relatives. The specific and robust
      biomarkers identified in this study could be introduced into routine clinical
      immunology or neurology departments to facilitate testing of patients with
      suspected ICF syndrome. In addition, as exemplified by two patients with a
      combination of molecular defects never described before, our data support the
      search for new types of mutations at the origin of ICF syndrome.

PMID- 24742018
TI  - Current utility of the ankle-brachial index (ABI) in general practice:
      implications for its use in cardiovascular disease screening.
AB  - BACKGROUND: Peripheral arterial disease (PAD) is a marker of systemic
      atherosclerosis and associated with a three to six fold increased risk of death
      from cardiovascular causes. Furthermore, it is typically asymptomatic and under
      diagnosed; this has resulted in escalating calls for the instigation of Primary
      Care PAD screening via Ankle Brachial Index (ABI) measurement. However, there is
      limited evidence regarding the feasibility of this and if the requisite core
      skills and knowledge for such a task already exist within primary care. This
      study aimed to determine the current utility of ABI measurement in general
      practices across Wales, with consideration of the implications for its use as a
      cardiovascular risk screening tool. METHOD: A self-reporting questionnaire was
      distributed to all 478 General Practices within Wales, sent via their responsible
      Health Boards. RESULTS: The survey response rate was 20%. ABI measurement is
      primarily performed by nurses (93%) for the purpose of wound management (90%). It
      is infrequently (73% < 4 times per month) and often incorrectly used (42% out of
      compliance with current ABI guidance). Only 52% of general practitioners and 16%
      of nurses reported that patients with an ABI of <= 0.9 require aggressive
      cardiovascular disease risk factor modification (as recommended by current
      national and international guidelines). CONCLUSION: ABI measurement is an under
      utilised and often incorrectly performed procedure in the surveyed general
      practices. Prior to its potential adoption as a formalised screening tool for
      cardiovascular disease, there is a need for a robust training programme with
      standardised methodology in order to optimise accuracy and consistency of
      results. The significance of a diagnosis of PAD, in terms of associated increased
      cardiovascular risk and the necessary risk factor modification, needs to be
      highlighted.

PMID- 24742019
TI  - Randomized controlled trial to evaluate the effects of ethyl-2-cyanoacrylate on
      pain intensity and quality of life in head and neck cancer patients suffering
      from cetuximab-induced rhagades during radioimmunotherapy: the support trial.
AB  - BACKGROUND: Cetuximab is a chimeric monoclonal antibody against the epidermal
      growth factor receptor (EGFR). Skin reactions are the most common side effects of
      cetuximab. Rhagades of the tips of the fingers and toes, the heels and especially
      the interphalangeal joints are one of the most frightening and painful
      dermatological side effects that may develop from EGFR-inhibitor therapy.
      Rhagades are characterized by pain, severe tenderness and poor healing response.
      They are challenging to treat. Thus, rhagades often poses the most significant
      threat to the quality of life (QoL) for these patients. Ethyl-2-cyanoacrylate
      (ECA), an ethyl ester of the 2-cyano-2-propenoic acid, is often used as adhesive
      in a variety of different work settings in industry, i.e. as a component in nail
      care products such as nail glue. In addition, ECA is used for various medical
      indications, such as for liquid bandages and for suture-less surgery. Wound
      healing can be accelerated with ECA. The purpose of the SUPPORT trial is to
      investigate the efficacy of ECA for the treatment of cetuximab-induced rhagades
      and to assess the clinical usefulness of the SUPO score, a new classification
      system for rhagades induced by EGFR-inhibitor therapy. METHODS/DESIGN: The
      SUPPORT trial is an open-label, prospective, randomized, national multicenter
      intervention study to evaluate the effectiveness of ECA versus the standard
      treatment of each institution on the pain intensity and QoL in patients with
      locally advanced head and neck cancer suffering from painful cetuximab-induced
      rhagades during radioimmunotherapy. Primary endpoint is the assessment of the
      pain intensity 24 hours after application of ECA or the standard treatment
      quantified by the visual analogue scale (VAS). Secondary endpoints are the
      evaluation of QoL assessed by the EORTC-QoL-C30 questionnaire and the
      Dermatological Life Quality Index (DLQI). DISCUSSION: During treatment with EGFR
      inhibitors it is necessary to recognize and manage side effects promptly to
      assure better patient QoL. The SUPPORT trial is the first randomized clinical
      trial evaluating a new treatment option for painful cetuximab-induced rhagades.
      Furthermore, the new SUPO score will be prospectively assessed in terms of
      clinical usefulness for classification of EGFR inhibitor-induced rhagades. TRIAL
      REGISTRATION: Current Controlled Trials NCT01693159.

PMID- 24742020
TI  - Role of caveolin-1 in asthma and chronic inflammatory respiratory diseases.
AB  - Caveolin-1 (Cav-1) is the major protein present in invaginations of the plasma
      membrane of cells known as caveolae. Cav-1 is expressed in numerous resident and
      inflammatory cells implicated in the pathogenesis of asthma and chronic
      inflammatory respiratory diseases including chronic obstructive pulmonary
      disease. A remarkable repertoire of functions has been identified for Cav-1 and
      these extend to, and have relevance to, asthma and chronic inflammatory
      respiratory diseases. Important processes influenced by Cav-1 include
      inflammation, fibrosis, smooth muscle contractility, regulation of apoptosis and
      cell senescence as well as epithelial barrier function and homeostasis. A better
      understanding of Cav-1 may be useful in developing new therapies for chronic
      inflammatory respiratory diseases.

PMID- 24742021
TI  - Motor imagery of gait: a new way to detect mild cognitive impairment?
AB  - OBJECTIVES: 1) To measure and compare the time required to perform (pTUG) and the
      time required to imagine (iTUG) the Timed Up & Go (TUG), and the time difference
      between these two tasks (i.e., TUG delta time) in older adults with cognitive
      decline (i.e., mild cognitive impairment (MCI) and mild-to-moderate Alzheimer
      disease and related disorders (ADRD)) and in cognitively healthy individuals
      (CHI); and 2) to examine any association between the TUG delta time and a
      cognitive status. METHODS: Sixty-six participants (24 CHI, 23 individuals with
      MCI, and 19 individuals with ADRD) were recruited in this cross-sectional study.
      The mean and standard deviation of the pTUG and iTUG completion times and the TUG
      delta time, as well as age, gender, and Mini-Mental State Examination (MMSE)
      scores were used as outcomes. Participants were separated into three groups based
      on the tertilization of TUG delta time: lowest (<13.6%; n = 22; best
      performance), intermediate (13.6-52.2%; n = 22), and highest tertile (>52.2%; n =
      22, worst performance). RESULTS: Fewer CHI were in the group exhibiting the
      highest tertile of TUG delta time compared to individuals with lowest and
      intermediate TUG delta times (p = 0.013). Being in the highest tertile of the TUG
      delta time was associated with cognitive decline in the unadjusted model (p =
      0.012 for MCI, and p = 0.021 for mild-to-moderate ADRD). In the multivariate
      models, this association remained significant only for individuals with MCI (p =
      0.019 while adjusting for age and gender; p = 0.047 while adjusting for age,
      gender, and MMSE score; p = 0.012 for the stepwise backward model). CONCLUSIONS:
      Our results provide the first evidence that motor imagery of gait may be used as
      a biomarker of MCI in older adults.

PMID- 24742022
TI  - Fokker-Planck and Fortet Equation-Based Parameter Estimation for a Leaky
      Integrate-and-Fire Model with Sinusoidal and Stochastic Forcing.
AB  - Analysis of sinusoidal noisy leaky integrate-and-fire models and comparison with
      experimental data are important to understand the neural code and neural
      synchronization and rhythms. In this paper, we propose two methods to estimate
      input parameters using interspike interval data only. One is based on numerical
      solutions of the Fokker-Planck equation, and the other is based on an integral
      equation, which is fulfilled by the interspike interval probability density. This
      generalizes previous methods tailored to stationary data to the case of time
      dependent input. The main contribution is a binning method to circumvent the
      problems of nonstationarity, and an easy-to-implement initializer for the
      numerical procedures. The methods are compared on simulated data. LIST OF
      ABBREVIATIONS LIF: Leaky integrate-and-fireISI: Interspike intervalSDE:
      Stochastic differential equationPDE: Partial differential equation.

PMID- 24742024
TI  - Adsorption and reactions of O2 on anatase TiO2.
AB  - CONSPECTUS: The interaction of molecular oxygen with titanium dioxide (TiO2)
      surfaces plays a key role in many technologically important processes such as
      catalytic oxidation reactions, chemical sensing, and photocatalysis. While O2
      interacts weakly with fully oxidized TiO2, excess electrons are often present in
      TiO2 samples. These excess electrons originate from intrinsic reducing defects
      (oxygen vacancies and titanium interstitials), doping, or photoexcitation and
      form polaronic Ti(3+) states in the band gap near the bottom of the conduction
      band. Oxygen adsorption involves the transfer of one or more of these excess
      electrons to an O2 molecule at the TiO2 surface. This results in an adsorbed
      superoxo (O2(-)) or peroxo (O2(2-)) species or in molecular dissociation and
      formation of two oxygen adatoms (2 * O(2-)). Oxygen adsorption is also the first
      step toward oxygen incorporation, a fundamental reaction that strongly affects
      the chemical properties and charge-carrier densities; for instance, it can
      transform the material from an n-type semiconductor to a poor electronic
      conductor. In this Account, we present an overview of recent theoretical work on
      O2 adsorption and reactions on the reduced anatase (101) surface. Anatase is the
      TiO2 polymorph that is generally considered most active in photocatalysis.
      Experiments on anatase powders have shown that the properties of photoexcited
      electrons are similar to those of excess electrons from reducing defects, and
      therefore, oxygen on reduced anatase is also a model system for studying the role
      of O2 in photocatalysis. Experimentally, the characteristic Ti(3+) defect states
      disappear after adsorption of molecular oxygen, which indicates that the excess
      electrons are indeed trapped by O2. Moreover, superoxide surface species
      associated with two different cation surface sites, possibly a regular cation
      site and a cation close to an anion vacancy, were identified by electron
      paramagnetic resonance spectroscopy. On the theoretical side, however, density
      functional theory studies have consistently found that it is energetically more
      favorable for O2 to adsorb in the peroxo form rather than the superoxo form. As a
      result, obtaining a detailed understanding of the nature of the observed
      superoxide species has proven difficult for many years. On reduced anatase (101),
      both oxygen vacancies and Ti interstitials have been shown to reside exclusively
      in the susbsurface. We discuss how reaction of O2 with a subsurface O vacancy
      heals the vacancy while leading to the formation of a surface bridging dimer
      defect. Similarly, the interaction of O2 with a Ti interstitial causes migration
      of this defect to the surface and the formation of a surface TiO2 cluster.
      Finally, we analyze the peroxo and superoxo states of the adsorbed molecule. On
      the basis of periodic hybrid functional calculations of interfacial electron
      transfer between reduced anatase and O2, we show that the peroxide form, while
      energetically more stable, is kinetically less favorable than the superoxide
      form. The existence of a kinetic barrier between the superoxo and peroxo states
      is essential for explaining a variety of experimental observations.

PMID- 24742025
TI  - Comprehensive multidimensional separations of peptides using nano-liquid
      chromatography coupled with micro free flow electrophoresis.
AB  - The throughput of existing liquid phase two-dimensional separations is generally
      limited by the peak capacity lost due to under sampling by the second dimension
      separation as peaks elute off the first dimension separation. In the current
      manuscript, a first dimension nanoliquid chromatography (nLC) separation is
      coupled directly with a second dimension micro free flow electrophoresis (MUFFE)
      separation. Since MUFFE performs continuous separations, no complicated injection
      or modulation is necessary to couple the two techniques. Analyte peaks are
      further separated in MUFFE as they elute off the nLC column. A side-on interface
      was designed to minimize dead volume in the nLC * MUFFE interface, eliminating
      this as a source of band broadening. A Chromeo P503 labeled tryptic digest of BSA
      was used as a complex mixture to assess peak capacity. 2D nLC * MUFFE peak
      capacities as high as 2,352 could be obtained in a 10 min separation window when
      determined according to the product of the first and second dimension peak
      capacities. After considering the orthogonality of the two separation modes and
      the fraction of separation space occupied by peaks, the usable peak capacity
      generated was determined to be 776. The 105 peaks/min generated using 2D nLC *
      MUFFE was nearly double the previously reported maximum peak capacity production
      rate achieved using online LC * LC. 

PMID- 24742026
TI  - Introducing a new azoaromatic pincer ligand. Isolation and characterization of
      redox events in its ferrous complexes.
AB  - The isolation and complete characterization of a new bis-azoaromatic ligand, 2,6
      bis(phenylazo)pyridine (L), are described, and its coordination to iron(II) is
      reported. A pseudo-trigonal-bipyramidal mixed-ligand complex of iron(II), FeLCl2
      (1), and a homoleptic octahedral iron complex, mer-[Fe(L)2]ClO4 [2]ClO4, have
      been synthesized from L and FeCl2 or hydrated Fe(ClO4)2, respectively, in boiling
      methanol. Determination of the X-ray crystallographic structure together with
      magnetic data (~ 5.06 MUB) and Mossbauer analysis of 1 established a high-spin
      Fe(II) complex ligated by one neutral 2,6-bis(phenylazo)pyridine ligand. The X
      ray crystallographic structure (showing dN-N > 1.30 A), Mossbauer data, and
      magnetic susceptibility measurements (~ 1.65 MUB) as well as a nearly isotropic
      EPR signal with only a small metal contribution at g = 1.968, on the other hand,
      suggest a low-spin Fe(II) complex with a one-electron-reduced radical ligand
      coordination in [2]ClO4. The ligand and the metal complexes have well-behaved
      redox properties, with the ligand(s) functioning as the redox-active site(s)
      responsible for redox events. The uncoordinated ligand, L, displays a reversible
      one-electron wave at -1.07 V and a quasi-reversible wave at -1.39 V. The
      partially reduced ligand L(*-) shows a single-line EPR spectrum at g = 2.001,
      signifying that L(*-) is a free radical. While complex 1 shows a reversible
      reduction at -0.08 V and an irreversible cathodic response at -0.98 V, the bis
      chelate [2]ClO4 undergoes a reversible one-electron oxidation at 0.54 V and three
      successive reversible one-electron reductions at -0.18, -0.88, and -1.2 V, all
      occurring at the ligands without affecting the metal ion oxidation state. The
      electronic structures of the parent monocationic complex [2](+) and its oxidized
      and reduced forms, generated by exhaustive electrolyses, have been characterized
      by using a host of spectroscopic techniques and density functional theory (DFT).
      It is found that the 2,6-bis(phenylazo)pyridine ligand (L) is truly redox
      noninnocent and is capable of coordinating transition-metal centers in its
      neutral ([L](0)), monoanionic monoradical ([L(*)](-)), and dianionic diradical
      ([L(**)](2-)) forms. 

PMID- 24742027
TI  - (Trans)Gender Role Expectations and Child Care in Samoa.
AB  - Samoan transgendered males are known as fa'afafine. Although Samoan women are
      characterized as the primary child care providers, fa'afafine report elevated
      willingness to invest in nieces and nephews compared to men and women. We
      hypothesized that Samoans hold unique transgender role expectations such that
      fa'afafine are expected to invest more toward nieces and nephews compared to
      others. Participants (N = 214) included Samoan men (30.23 years +/-8.19), women
      (30.00 years +/-10.93), and fa'afafine (30.25 years +/-7.45). For a variety of
      child care activities, participants nominated men, women, fa'afafine, or all
      three of these categories of individuals as responsible for investing toward
      nieces and nephews. Participants also reported how frequently their family
      members asked them to perform these activities for nieces and nephews.
      Responsibility for performing these activities was typically designated for
      women; men and women viewed fa'afafine as least responsible. Men's, but not
      fa'afafine's, family members asked them to allocate investment toward nieces and
      nephews more frequently. These findings are not consistent with the transgender
      role expectation hypothesis. Discussion details how the findings contribute to
      the literature on child care in Samoa. Alternate hypotheses for explaining why
      fa'afafine report elevated willingness to invest in nieces and nephews are
      considered. 

PMID- 24742028
TI  - Understanding the composition and activity of electrocatalytic nanoalloys in
      aqueous solvents: a combination of DFT and accurate neural network potentials.
AB  - The shape, size, and composition of catalyst nanoparticles can have a significant
      influence on catalytic activity. Understanding such structure-reactivity
      relationships is crucial for the optimization of industrial catalysts and the
      design of novel catalysts with enhanced properties. In this letter, we employ a
      combination of first-principles computations and large-scale Monte-Carlo
      simulations with highly accurate neural network potentials to study the
      equilibrium surface structure and composition of bimetallic Au/Cu nanoparticles
      (NPs), which have recently been of interest as stable and efficient CO2 reduction
      catalysts. We demonstrate that the inclusion of explicit water molecules at a
      first-principles level of accuracy is necessary to predict experimentally
      observed trends in Au/Cu NP surface composition; in particular, we find that Au
      coated core-shell NPs are thermodynamically favored in vacuum, independent of
      Au/Cu chemical potential and NP size, while NPs with mixed Au-Cu surfaces are
      preferred in aqueous solution. Furthermore, we show that both CO and O2
      adsorption energies differ significantly for NPs with the equilibrium surface
      composition found in water and those with the equilibrium surface composition
      found in vacuum, suggesting large changes in CO2 reduction activity. Our results
      emphasize the importance of understanding and being able to predict the effects
      of catalytic environment on catalyst structure and activity. In addition, they
      demonstrate that first-principles-based neural network potentials provide a
      promising approach for accurately investigating the relationships between
      solvent, surface composition and morphology, surface electronic structure, and
      catalytic activity in systems composed of thousands of atoms. 

PMID- 24742030
TI  - New transitional fossil snakeflies from China illuminate the early evolution of
      Raphidioptera.
AB  - BACKGROUND: Raphidioptera (snakeflies) is a holometabolous order of the
      superorder Neuropterida characterized by the narrowly elongate adult prothorax
      and the long female ovipositor. Mesozoic snakeflies were markedly more diverse
      than the modern ones are. However, the evolutionary history of Raphidioptera is
      largely unexplored, as a result of the poorly studied phylogeny among fossil and
      extant lineages within the order. RESULTS: In this paper, we report a new
      snakefly family, Juroraphidiidae fam. nov., based on exquisitely preserved
      fossils, attributed to a new species Juroraphidia longicollumgen. et sp. nov.,
      from the Jiulongshan Formation (Middle Jurassic) in Inner Mongolia, China. The
      new family is characterized by an unexpected combination of plesiomorphic and
      apomorphic characters of Raphidioptera. Based on our phylogenetic analysis,
      Juroraphidiidae fam. nov. together with Raphidiomorpha form a monophyletic clade,
      which is the sister to Priscaenigmatomorpha. The snakefly affinity of
      Priscaenigmatomorpha is confirmed and another new family, Chrysoraphidiidae fam.
      nov., is erected in this suborder. CONCLUSIONS: Juroraphidiidae fam. nov. is
      determined to be a transitional lineage between Priscaenigmatomorpha and
      Raphidiomorpha. Diversification of higher snakefly taxa had occurred by the Early
      Jurassic, suggesting that these insects had already had a long but undocumented
      history by this time.

PMID- 24742031
TI  - All-solid-state carbon nanotube torsional and tensile artificial muscles.
AB  - We report electrochemically powered, all-solid-state torsional and tensile
      artificial yarn muscles using a spinnable carbon nanotube (CNT) sheet that
      provides attractive performance. Large torsional muscle stroke (53 degrees /mm)
      with minor hysteresis loop was obtained for a low applied voltage (5 V) without
      the use of a relatively complex three-electrode electromechanical setup, liquid
      electrolyte, or packaging. Useful tensile muscle strokes were obtained (1.3% at
      2.5 V and 0.52% at 1 V) when lifting loads that are ~25 times heavier than can be
      lifted by the same diameter human skeletal muscle. Also, the tensile actuator
      maintained its contraction following charging and subsequent disconnection from
      the power supply because of its own supercapacitor property at the same time.
      Possible eventual applications for the individual tensile and torsional muscles
      are in micromechanical devices, such as for controlling valves and stirring
      liquids in microfluidic circuits, and in medical catheters. 

PMID- 24742033
TI  - Detection of the polyphenolic components in Ribes nigrum L.
AB  - BACKGROUND: The blackcurrant (Ribes nigrum L.) is a species of native currant
      which contains a lot of polyphenolic antioxidants which is used medicinally and
      has a fundamental role in the maintenance health. MATERIALS, METHODS AND
      OBJECTIVE: Ultraviolet-visible spectrophotometry and ultraviolet range high
      performance liquid chromatography (HPLC) were used to characterize the
      polyphenolic content of common Ribes nigrum collected in the western part of the
      Banat Region in Romania. RESULTS: UV-visible spectrophotometry was a reliable
      tool for identifying the phenolic compounds class. Polyphenols calibration curves
      from the methanolic extracts showed a good linearity (r(2)>0.984) within test
      ranges and generated a well-designed absorption band with a local maximum at
      273.2 nm band, which can be attributed to thr electronic transition of the n-pi*
      type. Chromatographic separation and analysis of the methanol extract was useful
      for the structural epigallocatechin (EGC) and epigallocatechin-3-gallate (EGCG)
      characterization of primary antioxidant compounds. CONCLUSIONS: The new, slightly
      modified, chromatographic system can serve for the development of a quantitative
      assessment methodology of epigallocatechin and epigallocatechin-3-gallate
      compounds, as well as for the comparative characterisation and standardisation of
      the dominant polyphenolic components in Ribes nigrum using EGC and EGCG
      standards.

PMID- 24742032
TI  - GPs' role security and therapeutic commitment in managing alcohol problems: a
      randomised controlled trial of a tailored improvement programme.
AB  - BACKGROUND: General practitioners with more positive role security and
      therapeutic commitment towards patients with hazardous or harmful alcohol
      consumption are more involved and manage more alcohol-related problems than
      others. In this study we evaluated the effects of our tailored multi-faceted
      improvement implementation programme on GPs' role security and therapeutic
      commitment and, in addition, which professional related factors influenced the
      impact of the implementation programme. METHODS: In a cluster randomised
      controlled trial, 124 GPs from 82 Dutch general practices were randomised to
      either the intervention or control group. The tailored, multi-faceted programme
      included combined physician, organisation, and patient directed alcohol-specific
      implementation strategies to increase role security and therapeutic commitment in
      GPs. The control group was mailed the national guideline and patients received
      feedback letters. Questionnaires were completed before and 12 months after start
      of the programme. We performed linear multilevel regression analysis to evaluate
      effects of the implementation programme. RESULTS: Participating GPs were
      predominantly male (63%) and had received very low levels of alcohol related
      education before start of the study (0.4 h). The programme increased therapeutic
      commitment (p = 0.005; 95%-CI 0.13 - 0.73) but not role security (p = 0.58; 95%
      CI -0.31 - 0.54). How important GPs thought it was to improve their care for
      problematic alcohol consumption, and the GPs' reported proportion of patients
      asked about alcohol consumption at baseline, contributed to the effect of the
      programme on therapeutic commitment. CONCLUSIONS: A tailored, multi-faceted
      programme aimed at improving GP management of patients with hazardous and harmful
      alcohol consumption improved GPs' therapeutic commitment towards patients with
      alcohol-related problems, but failed to improve GPs' role security. How important
      GPs thought it was to improve their care for problematic alcohol consumption, and
      the GPs' reported proportion of patients asked about alcohol consumption at
      baseline, both increased the impact of the programme on therapeutic commitment.
      It might be worthwhile to monitor proceeding of role security and therapeutic
      commitment throughout the year after the implementation programme, to see whether
      the programme is effective on short term but faded out on the longer term. TRIAL
      REGISTRATION: ClinicalTrials.gov Identifier: NCT00298220.

PMID- 24742034
TI  - Comparative performance of three sampling techniques to detect airborne
      Salmonella species in poultry farms.
AB  - Sampling techniques to detect airborne Salmonella species (spp.) in two pilot
      scale broiler houses were compared. Broilers were inoculated at seven days of age
      with a marked strain of Salmonella enteritidis. The rearing cycle lasted 42 days
      during the summer. Airborne Salmonella spp. were sampled weekly using impaction,
      gravitational settling, and impingement techniques. Additionally, Salmonella spp.
      were sampled on feeders, drinkers, walls, and in the litter. Environmental
      conditions (temperature, relative humidity, and airborne particulate matter (PM)
      concentration) were monitored during the rearing cycle. The presence of
      Salmonella spp. was determined by culture-dependent and molecular methods. No
      cultivable Salmonella spp. were recovered from the poultry houses' surfaces, the
      litter, or the air before inoculation. After inoculation, cultivable Salmonella
      spp. were recovered from the surfaces and in the litter. Airborne cultivable
      Salmonella spp. Were detected using impaction and gravitational settling one or
      two weeks after the detection of Salmonella spp. in the litter. No cultivable
      Salmonella spp. were recovered using impingement based on culture-dependent
      techniques. At low airborne concentrations, the use of impingement for the
      quantification or detection of cultivable airborne Salmonella spp. is not
      recommended. In these cases, a combination of culture-dependent and culture
      independent methods is recommended. These data are valuable to improve current
      measures to control the transmission of pathogens in livestock environments and
      for optimising the sampling and detection of airborne Salmonella spp. in
      practical conditions.

PMID- 24742035
TI  - Respiratory symptoms and functions in barn workers.
AB  - INTRODUCTION AND AIM: The presented study was undertaken to investigate the
      respiratory health problems in family barns with one or more cows and at least
      one family member working in the barn. METHODS: 150 workers (128 female, 22 male)
      from 4 villages of Yigilca district near the city of Duzce in north-west Turkey
      were enrolled in this study between October - December 2011. An Occupational and
      Environmental Chest Diseases questionnaire developed by the American Thoracic
      Society, pulmonary function test, physical examination and investigation for
      nasal eosinophil were performed in all subjects. RESULTS: The mean age of workers
      was 47.7 +/- 14.2 years. Cough was present in 24% of subjects. The rates of
      phlegm, wheezing, chest tightness and dyspnea were 13.3%, 6%, 6% and 27.3%,
      respectively. Obstructive ventilatory pattern was observed in 37 workers (24.6%).
      43 workers (28.6%) showed restrictive ventilatory pattern. Nasal eosinophilia was
      detected in 47.3% (71/150) of the subjects. Pulmonary functions of workers with
      nasal eosinophilia did not differ from the other workers. There were
      statistically significant negative correlations between the duration of working
      in barns and respiratory functions. CONCLUSIONS: Pulmonary functions of barn
      workers have been found to be decreased related to the duration of barn working.
      Furthermore, respiratory symptoms increased in relation with both barn working
      and biomass consumption. Precautions should therefore be taken to ventilate both
      barns and houses.

PMID- 24742036
TI  - Occurrence of non-fermenting gram negative bacteria in drinking water dispensed
      from point-of-use microfiltration devices.
AB  - INTRODUCTION AND OBJECTIVE: Many devices have been marketed in order to improve
      the organoleptic characteristics of tap water resulting from disinfection with
      chlorine derivates. The aim of the presented study was to assess the degree of
      contamination by non-fermenting Gram-negative bacteria (NF-GNB) of drinking water
      dispensed from microfiltration devices at point-of-use. METHODS: Water samples
      were collected from 94 point-of-use water devices fitted with a filter (0.5 MUm
      pore size) containing powdered activated carbon. The microbiological
      contamination of water entering and leaving the microfiltered water dispensers
      was compared. The NF-GNB loads were correlated to Total Heterotrophic Counts
      (HPCs) at 37 and 22  degrees C, residua chlorine, and some structural and
      functional features of the devices. RESULTS: NF-GNB were detected from 23% of
      supply water samples, 33% of still unchilled water, 33% of still chilled water
      and 18% of carbonated chilled water. The most frequent isolates were
      Pseudomonadaceae: Steno.maltophilia 30.2% of isolates, Pseudomonas 20.5%, Delftia
      acidovorans 13.4%, while the species more largely distributed was Ps. aeruginosa
      recovered from 13% of samples. The distribution of the various NF-GNB was
      different in the water entering and in that leaving the devices. Ps.aeruginosa
      and Steno.maltophilia were the predominant species in water leaving the
      microfiltration dispensers, probably due to their capacity to colonize the
      circuits and to prevail over the others. Recovery of NF-GNB was favoured by the
      reduction in residual chlorine of the supply water, occasional use, the absence
      of a bacteriostatic element in the filter and inadequate disinfection of the
      water lines. CONCLUSIONS: The presence of high concentrations of potentially
      pathogenic species of NF-GNB (Ps.aeruginosa, Steno. maltophilia, Burkhol.cepacia)
      in the water dispensed from microfiltration devices represents a risk of
      waterborne infections for vulnerable individuals. When these devices are used in
      environments such as hospitals, nursing homes for the elderly, etc.,
      microbiological monitoring for the detection of NF-GNB is advisable.

PMID- 24742037
TI  - Assessment of viability of the nematode eggs (Ascaris, Toxocara, Trichuris) in
      sewage sludge with the use of LIVE/DEAD Bacterial Viability Kit.
AB  - Sewage sludges from wastewater treatment plants may contain live parasite eggs,
      which can be a source of humans and animals infection. According to the current
      rules, parasitological examination includes detection of the Ascaris spp.,
      Trichuris spp. and Toxocara spp. eggs and estimation of their viability. The
      viability assessment based only on the incubation and observation of isolated egg
      is long and imprecise. The aim of this study was to develop sensitive and less
      labour-intensive methods for assessing viability of Ascaris spp., Toxocara spp.
      and Trichuris spp. eggs in sewage sludge. For this purpose, LIVE/DEAD Kit was
      used. Firstly, the possibility of distinguishing between live and dead eggs in
      water was assessed. Secondly, an appropriate amount of dyeing mixture needed to
      distinguish the live and dead eggs in the sewage sludge was determined using
      experimentally enriched samples and naturally contaminated samples of sludge.
      Eggs were isolated from the samples by own method which was a combination of
      flotation and sedimentation, preceded by a long mixing. After the last stage of
      the procedure, sediment containing the eggs of parasites was stained by LIVE/DEAD
      kit according to the manufacturer instructions, but with the use of different
      variants of dyes mixture concentration. The investigation showed that live and
      dead eggs of these three parasites could be differed by this method with the use
      of proper concentration of dyes. Live eggs were stained in green (Ascaris and
      Trichuris) and green-blue (Toxocara). However, all types of dead eggs were red
      coloured. The study demonstrated that after some modifications (resulted from the
      nature of the samples) the LIVE/DEAD kit is useful for assessing the viability of
      Toxocara, Ascaris and Trichuris eggs occurring in the sludge.

PMID- 24742038
TI  - Hot flushes, hormone therapy and alternative treatments: 30 years of experience
      from Sweden.
AB  - OBJECTIVES: The use of hormone therapy (HT) for hot flushes has changed
      dramatically over the past five decades. In this cross-sectional questionnaire
      study, the aim was to describe the use of HT and alternative treatments and to
      study the frequency of hot flushes. A further aim was to compare data from the
      present questionnaire with data from previous studies made in the same geographic
      area. METHOD: A questionnaire was sent to a random sample of 2000 women aged 47
      56 years living in Ostergotland County, Sweden. The results were compared with
      findings from previous studies regarding use of HT, alternative treatment and hot
      flushes, and the number of HT prescriptions dispensed during the corresponding
      time using data derived from the Swedish Prescribed Drug Registry. RESULTS: The
      response rate was 66%. Six percent used HT, in line with prevalence data from the
      Swedish Prescribed Drug Registry. Alternative treatments were used by 10%. About
      70% of postmenopausal women reported flushes and almost one-third of those with
      flushes stated that they would be positive to HT if therapy could be shown to be
      harmless, a view more often stated by women with severe complaints of hot flushes
      (67%). CONCLUSION: The use of HT and alternative treatments is low and many women
      suffer from flushes that could be treated. Women considered their knowledge of
      the climacteric period and treatment options as insufficient. Individualized
      information should be given and women with significant climacteric complaints,
      without contraindications, should be given the opportunity to try HT.

PMID- 24742040
TI  - Our tiny organization packs a national wallop.

PMID- 24742041
TI  - Widespread movement of invasive cattle fever ticks (Rhipicephalus microplus) in
      southern Texas leads to shared local infestations on cattle and deer.
AB  - BACKGROUND: Rhipicephalus (Boophilus) microplus is a highly-invasive tick that
      transmits the cattle parasites (Babesia bovis and B. bigemina) that cause cattle
      fever. R. microplus and Babesia are endemic in Mexico and ticks persist in the
      United States inside a narrow tick eradication quarantine area (TEQA) along the
      Rio Grande. This containment area is threatened by unregulated movements of
      illegal cattle and wildlife like white-tailed deer (WTD; Odocoileus virginianus).
      METHODS: Using 11 microsatellite loci we genotyped 1,247 R. microplus from 63
      Texas collections, including outbreak infestations from outside the TEQA. We used
      population genetic analyses to test hypotheses about ecological persistence, tick
      movement, and impacts of the eradication program in southern Texas. We tested
      acaricide resistance with larval packet tests (LPTs) on 47 collections. RESULTS:
      LPTs revealed acaricide resistance in 15/47 collections (32%); 11 were outside
      the TEQA and three were resistant to multiple acaricides. Some collections highly
      resistant to permethrin were found on cattle and WTD. Analysis of genetic
      differentiation over time at seven properties revealed local gene pools with very
      low levels of differentiation (FST 0.00-0.05), indicating persistence over
      timespans of up to 29 months. However, in one neighborhood differentiation varied
      greatly over a 12-month period (FST 0.03-0.13), suggesting recurring immigration
      from distinct sources as another persistence mechanism. Ticks collected from
      cattle and WTD at the same location are not differentiated (FST = 0), implicating
      ticks from WTD as a source of ticks on cattle (and vice versa) and emphasizing
      the importance of WTD to tick control strategies. We identified four major
      genetic groups (K = 4) using Bayesian population assignment, suggesting multiple
      introductions to Texas. CONCLUSIONS: Two dispersal mechanisms give rise to new
      tick infestations: 1) frequent short-distance dispersal from the TEQA; and 2)
      rare long-distance, human-mediated dispersal from populations outside our study
      area, probably Mexico. The threat of cattle fever tick transport into Texas is
      increased by acaricide resistance and the ability of R. microplus to utilize WTD
      as an alternate host. Population genetic analyses may provide a powerful tool for
      tracking invasions in other parts of the world where these ticks are established.

PMID- 24742042
TI  - Triptolide induces apoptotic cell death of human cholangiocarcinoma cells through
      inhibition of myeloid cell leukemia-1.
AB  - BACKGROUND: Cholangiocarcinoma (CCA), a devastating neoplasm, is highly resistant
      to current chemotherapies. CCA cells frequently overexpress the antiapoptotic
      protein myeloid cell leukemia-1(Mcl-1), which is responsible for its
      extraordinary ability to evade cell death. Triptolide, a bioactive ingredient
      extracted from Chinese medicinal plant, has been shown to inhibit cell
      proliferation and induce apoptosis in several cancers. METHODS: CCK-8 assay was
      performed to detect cell survival rate in vitro. DAPI staining and Flow cytometry
      were used to analyze apoptosis. Western blot was performed to determine the
      expression levels of caspase-3, caspase-7, caspase-9, PARP, and Mcl-1.
      Quantitative real-time PCR and immunofluorescence were used to detect the
      expression levels of Mcl-1. The nude mice xenograft model was used to evaluate
      the antitumor effect of triptolide in vivo. RESULTS: Triptolide reduced cell
      viability in cholangiocarcinoma cell lines in a dose- and time-dependent manner,
      with IC50 values of 12.6 +/- 0.6 nM, 20.5 +/- 4.2 nM, and 18.5 +/- 0.7 nM at 48 h
      for HuCCT1, QBC939, and FRH0201 respectively. Triptolide induced apoptosis in CCA
      cell lines in part through mitochondrial pathway. Using quantitative real-time
      PCR, western blot and immunofluorescence, we have shown that triptolide
      downregulates Mcl-1 mRNA and protein levels. Furthermore, triptolide inhibited
      the CCA growth in vivo. CONCLUSIONS: Triptolide has profound antitumor effect on
      CCA, probably by inducing apoptosis through inhibition of Mcl-1. Triptolide would
      be a promising therapeutic agent for CCA.

PMID- 24742043
TI  - Phenotype and frequency of STUB1 mutations: next-generation screenings in
      Caucasian ataxia and spastic paraplegia cohorts.
AB  - BACKGROUND: Mutations in the gene STUB1, encoding the protein CHIP (C-terminus of
      HSC70-interacting protein), have recently been suggested as a cause of recessive
      ataxia based on the findings in few Chinese families. Here we aimed to
      investigate the phenotypic and genotypic spectrum of STUB1 mutations, and to
      assess their frequency in different Caucasian disease cohorts. METHODS: 300
      subjects with degenerative ataxia (n = 167) or spastic paraplegia (n = 133) were
      screened for STUB1 variants by whole-exome-sequencing (n = 204) or shotgun
      fragment-library-sequencing (n = 96). To control for the specificity of STUB1
      variants, we screened an additional 1707 exomes from 891 index families with
      other neurological diseases. RESULTS: We identified 3 ataxia patients (3/167 =
      1.8%) with 4 novel missense mutations in STUB1, including 3 mutations in its
      tetratricopeptide-repeat domain. All patients showed evidence of pyramidal tract
      damage. Cognitive impairment was present only in one and hypogonadism in none of
      them. Ataxia did not start before age 48 years in one subject. No recessive STUB1
      variants were identified in families with other neurological diseases,
      demonstrating that STUB1 variants are not simply rare polymorphisms ubiquitous in
      neurodegenerative disease. CONCLUSIONS: STUB1-disease occurs also in Caucasian
      ataxia populations (1.8%). Our results expand the genotypic spectrum of STUB1
      disease, showing that pathogenic mutations affect also the tetratricopeptide
      repeat domain, thus providing clinical evidence for the functional importance of
      this domain. Moreover, they further delineate the phenotypic core features of
      STUB1-ataxia. Pyramidal tract damage is a common accompanying feature and can
      include lower limb spasticity, thus adding STUB1-ataxia to the differential
      diagnosis of "spastic ataxias". However, STUB1 is rare in subjects with
      predominant spastic paraplegia (0/133). In contrast to previous reports, STUB1
      ataxia can start even above age 40 years, and neither hypogonadism nor prominent
      cognitive impairment are obligatory features.

PMID- 24742044
TI  - How uncertainty bounds the shape index of simple cells.
AB  - We propose a theoretical motivation to quantify actual physiological features,
      such as the shape index distributions measured by Jones and Palmer in cats and by
      Ringach in macaque monkeys. We will adopt the uncertainty principle associated to
      the task of detection of position and orientation as the main tool to provide
      quantitative bounds on the family of simple cells concretely implemented in
      primary visual cortex.Mathematics Subject Classification (2000)2010: 62P10,
      43A32, 81R15. 

PMID- 24742045
TI  - Resolving the titer of murine cytomegalovirus by plaque assay using the M2-10B4
      cell line and a low viscosity overlay.
AB  - BACKGROUND: Murine cytomegalovirus (MCMV) is increasingly used as an infectious
      model to investigate host-pathogen interactions in mice. Detailed methods have
      been published for using primary murine embryonic fibroblasts (MEFs) for
      preparing stocks and determining viral titers of MCMV. For determining the titer
      of MCMV by plaque assay, these methods rely on a high viscosity media that
      restricts viral spreading through the supernatant of the culture, but is also
      usually too viscous to pipet. Moreover, MEFs must be repeatedly generated and can
      vary widely from batch-to-batch in purity, proliferation rates, and the
      development of senescence. In contrast, the M2-10B4 bone marrow stromal cell line
      (ATCC # CRL-1972), which is also permissive for MCMV, has been reported to
      produce high-titer stocks of MCMV and has the considerable advantages of growing
      rapidly and consistently. However, detailed methods using these cells have not
      been published. METHODS: We modified existing protocols to use M2-10B4 cells for
      measuring MCMV titers by plaque assay. RESULTS: We found that MCMV plaques could
      be easily resolved on monolayers of M2-10B4 cells. Moreover, plaques formed
      normally even when cultures of M2-10B4 cells were less than 50% confluent on the
      day of infection, as long as we also used a reduced viscosity overlay.
      CONCLUSIONS: Overall, our protocol enabled us to use a consistent cell line to
      assess viral titers, rather than repeatedly producing primary MEFs. It also
      allowed us to start the assay with 4-fold fewer cells than would be required to
      generate a confluent monolayer, reducing the lead-time prior to the start of the
      assay. Finally, the reduced viscosity CMC could be handled by pipet and did not
      need to be pre-mixed with media, thus increasing its shelf-life and ease-of-use.
      We describe our results here, along with detailed protocols for the use of the M2
      10B4 cell lines to determine the titer and grow stocks of MCMV.

PMID- 24742046
TI  - "It's alright to ask for help": findings from a qualitative study exploring the
      information and support needs of family carers at the end of life.
AB  - BACKGROUND: Family carers play an essential role in providing end-of-life care to
      their relatives but have been found to experience uncertainty and a lack of
      confidence in fulfilling their caregiving roles, prompting recent calls for
      educational or information based resources to be developed for carers. METHODS:
      We carried out four focus groups with Clinical Nurse Specialists, healthcare
      assistants, former and current carers at a hospice in the UK, to explore the
      information and support needs of family carers. RESULTS: Our findings support
      previous research by highlighting a number of care situations where carers
      experience uncertainty and could seemingly benefit from greater information or
      instruction. Three main themes were identified which reflected carer experiences
      and needs in relation to potential information giving or educational
      interventions. These have been described as the knowledge and competence of
      carers; the preparedness of carers and low levels of carer identification with,
      and confidence in their roles as 'carers', which influences help seeking
      behaviours; and in turn how potential supportive interventions might be received
      by carers. CONCLUSIONS: Family carers experience multiple needs for information
      and education, but meeting these needs remains a challenge. Our results suggest
      three domains which could underpin this type of intervention: developing
      knowledge and competence; facilitating preparedness; supporting role recognition
      and confidence building. We recommend an integrated information giving approach
      which addresses these domains by combining a resource pack for carers with a more
      explicit acknowledging role for health professionals. Together these could
      provide key information and also build confidence amongst family carers to ask
      for further support and advice as needed.

PMID- 24742047
TI  - KCNK3: new gene target for pulmonary hypertension?
AB  - Recently, KCNK3 has been identified as a new predisposing gene for pulmonary
      arterial hypertension (PAH) by whole-exome sequencing. Mutation in KCNK3 gene is
      responsible for the first channelopathy identified in PAH. PAH due to KCNK3
      mutations is an autosomal dominant disease with an incomplete penetrance as
      previously described in PAH due to BMPR2 mutations. This discovery represents an
      important advance for genetic counselling, allowing identification of high risk
      relatives for PAH and possible screening for PAH in KCNK3 mutation carriers. 

PMID- 24742048
TI  - Transmetalation of aqueous inorganic clusters: a useful route to the synthesis of
      heterometallic aluminum and indium hydroxo-aquo clusters.
AB  - [AlxIny(MU3-OH)6(MU-OH)18(H2O)24](NO3)15 hydroxy-aquo clusters (AlxIn13-x) are
      synthesized through the evaporation of stoichiometrically varied solutions of
      Al13 and In(NO3)3 using a transmetalation reaction. Several spectroscopic
      techniques ((1)H NMR, (1)H-diffusion ordered spectroscopy, dynamic light
      scattering, and Raman) are used to compare AlxIn13-x to its Al13 counterpart. A
      thin film of aluminum indium oxide was prepared from an Al7In6 cluster ink,
      showing its utility as a precursor for materials. 

PMID- 24742049
TI  - Engineering responsive polymer building blocks with host-guest molecular
      recognition for functional applications.
AB  - CONSPECTUS: All living organisms and soft matter are intrinsically responsive and
      adaptive to external stimuli. Inspired by this fact, tremendous effort aiming to
      emulate subtle responsive features exhibited by nature has spurred the invention
      of a diverse range of responsive polymeric materials. Conventional stimuli
      responsive polymers are constructed via covalent bonds and can undergo reversible
      or irreversible changes in chemical structures, physicochemical properties, or
      both in response to a variety of external stimuli. They have been imparted with a
      variety of emerging applications including drug and gene delivery, optical
      sensing and imaging, diagnostics and therapies, smart coatings and textiles, and
      tissue engineering. On the other hand, in comparison with molecular chemistry
      held by covalent bonds, supramolecular chemistry built on weak and reversible
      noncovalent interactions has emerged as a powerful and versatile strategy for
      materials fabrication due to its facile accessibility, extraordinary
      reversibility and adaptivity, and potent applications in diverse fields.
      Typically involving more than one type of noncovalent interactions (e.g.,
      hydrogen bonding, metal coordination, hydrophobic association, electrostatic
      interactions, van der Waals forces, and pi-pi stacking), host-guest recognition
      refers to the formation of supramolecular inclusion complexes between two or more
      entities connected together in a highly controlled and cooperative manner. The
      inherently reversible and adaptive nature of host-guest molecular recognition
      chemistry, stemming from multiple noncovalent interactions, has opened up a new
      platform to construct novel types of stimuli-responsive materials. The
      introduction of host-guest chemistry not only enriches the realm of responsive
      materials but also confers them with promising new applications. Most
      intriguingly, the integration of responsive polymer building blocks with host
      guest recognition motifs will endow the former with further broadened
      responsiveness to external stimuli and accordingly more sophisticated functions.
      In this Account, we summarize recent progress in the field of responsive
      polymeric materials containing host-guest recognition motifs with selected
      examples and highlight their versatile functional applications, whereas small
      molecule-oriented host-guest supramolecular systems are excluded. We demonstrate
      how the introduction of host-guest chemistry into conventional polymer systems
      can modulate their responsive modes to external stimuli. Moreover, the responsive
      specificity and selectivity of polymeric systems can also be inherited from the
      host-guest recognition motifs, and these features provide extra advantages in
      terms of function integration. The following discussions are categorized in terms
      of design and functions, namely, host-guest chemistry toward the fabrication of
      responsive polymers and assemblies, optical sensing and imaging, drug and gene
      delivery, and self-healing materials. A concluding remark on future developments
      is also presented. We wish this prosperous field would incur more original and
      evolutionary ideas and benefit fundamental research and our daily life in a more
      convenient way.

PMID- 24742051
TI  - One-pot synthesis of 2,4-disubstituted indoles from N-tosyl-2,3-dichloroaniline
      using palladium-dihydroxyterphenylphosphine catalyst.
AB  - 4-Chloroindoles were synthesized from readily available 2,3-dichloroaniline
      derivatives and terminal alkynes. The catalyst composed of palladium and
      dicyclohexyl(dihydroxyterphenyl)phosphine (Cy-DHTP) enabled ortho-selective
      Sonogashira coupling, and subsequent cyclization afforded 4-chloroindoles in high
      yields. This transformation was successfully applied to the one-pot synthesis of
      2,4-disubstituted indoles via Suzuki-Miyaura coupling after indole formation. 

PMID- 24742052
TI  - How do heterosexual undergraduate students define having sex? A new approach to
      an old question.
AB  - This study examined how people define having sex utilizing a new approach to this
      area of research. A total of 267 men and 327 women rated their degree of
      confidence that engaging in each of 21 physically intimate behaviors (e.g.,
      penile-vaginal intercourse) counted as "having sex" and then qualitatively
      explained their reasoning. Separate ratings were made for each behavior when
      engaged in by the respondent and by his or her partner with someone else. Results
      showed that, as in previous studies, for both sexes, some behaviors (e.g., penile
      vaginal intercourse) were far more confidently rated (i.e., "definitely sex")
      than were others (e.g., oral-genital stimulation). Further, both men and women
      were significantly more certain that a behavior counted as "having sex" when
      considering their partner's behavior outside the relationship than when they
      considered their own behavior. Finally, the order in which the two scenarios
      (i.e., self versus partner) was presented significantly affected participants'
      certainty. Qualitative results, paired with quantitative findings, suggest that
      individuals consider a variety of contextual factors when making these
      definitional decisions. The methodological and sexual health implications of
      these results are discussed. 

PMID- 24742053
TI  - 6S RNA, a global regulator of transcription in Escherichia coli, Bacillus
      subtilis, and beyond.
AB  - 6S RNA is a small, noncoding RNA that interacts with the primary holoenzyme form
      of RNA polymerase. Escherichia coli 6S RNA is a global regulator that
      downregulates transcription and is important for modulating stress and optimizing
      survival during nutrient limitation. Studies in diverse organisms suggest a
      higher complexity in function than previously appreciated. Some bacteria have
      multiple 6S RNAs that appear to have independent functions. 6S RNA accumulation
      profiles also are quite divergent and suggest they integrate into cellular
      networks in a species-specific manner. Nevertheless, in all tested systems the
      common theme is a role for 6S RNA in survival. Finally, there has been much
      excitement about the ability of 6S RNA to be used as a template to synthesize
      product RNAs (pRNAs). This review highlights the details of 6S RNA in E. coli and
      compares and contrasts 6S RNAs in multiple species. 

PMID- 24742055
TI  - Adaptive plasticity in the mouse mandible.
AB  - BACKGROUND: Plasticity, i.e. non-heritable morphological variation, enables
      organisms to modify the shape of their skeletal tissues in response to varying
      environmental stimuli. Plastic variation may also allow individuals to survive in
      the face of new environmental conditions, enabling the evolution of heritable
      adaptive traits. However, it is uncertain whether such a plastic response of
      morphology constitutes an evolutionary adaption itself. Here we investigate
      whether shape differences due to plastic bone remodelling have functionally
      advantageous biomechanical consequences in mouse mandibles. Shape characteristics
      of mandibles from two groups of inbred laboratory mice fed either rodent pellets
      or ground pellets mixed with jelly were assessed using geometric morphometrics
      and mechanical advantage measurements of jaw adductor musculature. RESULTS:
      Mandibles raised on diets with differing food consistency showed significant
      differences in shape, which in turn altered their biomechanical profile. Mice
      raised on a soft food diet show a reduction in mechanical advantage relative to
      mice of the same inbred strain raised on a typical hard food diet. Further, the
      soft food eaters showed lower levels of integration between jaw regions,
      particularly between the molar and angular region relative to hard food eaters.
      CONCLUSIONS: Bone remodelling in mouse mandibles allows for significant shifts in
      biomechanical ability. Food consistency significantly influences this process in
      an adaptive direction, as mice raised on hard food develop jaws better suited to
      handle hard foods. This remodelling also affects the organisation of the
      mandible, as mice raised on soft food appear to be released from developmental
      constraints showing less overall integration than those raised on hard foods, but
      with a shift of integration towards the most solicited regions of the mandible
      facing such a food, namely the incisors. Our results illustrate how
      environmentally driven plasticity can lead to adaptive functional changes that
      increase biomechanical efficiency of food processing in the face of an increased
      solicitation. In contrast, decreased demand in terms of food processing seems to
      release developmental interactions between jaw parts involved in mastication, and
      may generate new patterns of co-variation, possibly opening new directions to
      subsequent selection. Overall, our results emphasize that mandible shape and
      integration evolved as parts of a complex system including mechanical loading
      food resource utilization and possibly foraging behaviour.

PMID- 24742056
TI  - Enhancing nanoparticle electrodynamics with gold nanoplate mirrors.
AB  - Mirrors and optical cavities can modify and enhance matter-radiation
      interactions. Here we report that chemically synthesized Au nanoplates can serve
      as micrometer-size mirrors that enhance electrodynamic interactions. Because of
      their plasmonic properties, the Au nanoplates enhance the brightness of scattered
      light from Ag nanoparticles near the nanoplate surface in dark-field microscopy.
      More importantly, enhanced optical trapping and optical binding of Ag
      nanoparticles are demonstrated in interferometric optical traps created from a
      single laser beam and its reflection from individual Au nanoplates. The
      enhancement of the interparticle force constant is ~20-fold more than expected
      from the increased intensity due to standing wave interference. We show that the
      additional stability for optical binding arises from the restricted axial thermal
      motion of the nanoparticles that couples to and reduces the fluctuations in the
      lateral plane. This new mechanism greatly advances the photonic synthesis of
      ultrastable nanoparticle arrays and investigation of their properties. 

PMID- 24742054
TI  - Viral miniproteins.
AB  - Many viruses encode short transmembrane proteins that play vital roles in virus
      replication or virulence. Because many of these proteins are less than 50 amino
      acids long and not homologous to cellular proteins, their open reading frames
      were often overlooked during the initial annotation of viral genomes. Some of
      these proteins oligomerize in membranes and form ion channels. Other miniproteins
      bind to cellular transmembrane proteins and modulate their activity, whereas
      still others have an unknown mechanism of action. Based on the underlying
      principles of transmembrane miniprotein structure, it is possible to build
      artificial small transmembrane proteins that modulate a variety of biological
      processes. These findings suggest that short transmembrane proteins provide a
      versatile mechanism to regulate a wide range of cellular activities, and we
      speculate that cells also express many similar proteins that have not yet been
      discovered. 

PMID- 24742057
TI  - Diagnostic characteristics and prognoses of primary-care patients referred for
      clinical exercise testing: a prospective observational study.
AB  - BACKGROUND: Evaluation of angina symptoms in primary care often includes clinical
      exercise testing. We sought to identify clinical characteristics that predicted
      the outcome of exercise testing and to describe the occurrence of cardiovascular
      events during follow-up. METHODS: This study followed patients referred to
      exercise testing for suspected coronary disease by general practitioners in the
      County of Jamtland, Sweden (enrolment, 25 months from February 2010). Patient
      characteristics were registered by pre-test questionnaire. Exercise tests were
      performed with a bicycle ergometer, a 12-lead electrocardiogram, and validated
      scales for scoring angina symptoms. Exercise tests were classified as positive
      (ST-segment depression >1 mm and chest pain indicative of angina), non-conclusive
      (ST depression or chest pain), or negative. Odds ratios (ORs) for exercise-test
      outcome were calculated with a bivariate logistic model adjusted for age, sex,
      systolic blood pressure, and previous cardiovascular events. Cardiovascular
      events (unstable angina, myocardial infarctions, decisions on revascularization,
      cardiovascular death, and recurrent angina in primary care) were recorded within
      six months. A probability cut-off of 10% was used to detect cardiovascular events
      in relation to the predicted test outcome. RESULTS: We enrolled 865 patients
      (mean age 63.5 years, 50.6% men); 6.4% of patients had a positive test, 75.5%
      were negative, 16.4% were non-conclusive, and 1.7% were not assessable. Positive
      or non-conclusive test results were predicted by exertional chest pain (OR 2.46,
      95% confidence interval (CI) 1.69-3.59), a pathologic ST-T segment on resting
      electrocardiogram (OR 2.29, 95% CI 1.44-3.63), angina according to the patient
      (OR 1.70, 95% CI 1.13-2.55), and medication for dyslipidaemia (OR 1.51, 95% CI
      1.02-2.23). During follow-up, cardiovascular events occurred in 8% of all
      patients and 4% were referred to revascularization. Cardiovascular events
      occurred in 52.7%, 18.3%, and 2% of patients with positive, non-conclusive, or
      negative tests, respectively. The model predicted 67/69 patients with a
      cardiovascular event. CONCLUSIONS: Clinical characteristics can be used to
      predict exercise test outcome. Primary care patients with a negative exercise
      test have a very low risk of cardiovascular events, within six months. A
      predictive model based on clinical characteristics can be used to refine the
      identification of low-risk patients.

PMID- 24742058
TI  - Reasons for refusing cataract surgery in illiterate individuals in a tribal area
      of Andhra Pradesh, India.
AB  - PURPOSE: To assess the reasons for refusing cataract surgery in illiterate
      individuals in a tribal area of India. METHODS: A prospective study evaluated
      1046 subjects who had undergone screening in eye camps and included 398 of 492
      referred subjects with cataract who refused to seek cataract surgery. Subjects
      were assessed to elicit general and specific reasons for non-compliance. Multiple
      logistic regression analysis was applied to determine the associations; p < 0.05
      was considered significant. RESULTS: Overall, 83% (329/398) of subjects reported
      that they could manage with their current vision. The five most common reasons
      they did not proceed with cataract surgery were: fear of losing current vision,
      work priority, lack of support systems, a dependency due to old age, and expenses
      required after surgery. Odds of seeking treatment were lower among unemployed
      subjects (odds ratio, OR, 0.4, 95% confidence interval, CI, 0.19-0.86; p = 0.01)
      and in patients with family income <1000 Indian rupees per month (OR 0.5, 95% CI
      0.34-0.94; p = 0.02), and higher among those unilaterally blind (OR 10.8, 95% CI
      3.3-35.6; p <= 0.01). CONCLUSION: In a tribal setting, 83% of individuals
      referred for cataract surgery did not proceed with surgery. Reasons given for non
      compliance were not directly related to the surgery but focused on valid day-to
      day difficulties anticipated to increase following surgery. Beyond accessibility
      and cost of surgery, other social and infrastructural factors need to be
      addressed to increase the uptake of cataract surgery.

PMID- 24742059
TI  - Prevalence of amblyopia and strabismus in a population of 7th-grade junior high
      school students in Central China: the Anyang Childhood Eye Study (ACES).
AB  - PURPOSE: To determine the prevalence of amblyopia and strabismus in 7th-grade
      junior high school students in central China. METHODS: Using stratified cluster
      sampling, 2363 7th-grade students were recruited from four junior high schools in
      Anyang city into the cross-sectional Anyang Childhood Eye Study (ACES). All
      students underwent visual acuity (VA), cycloplegic autorefraction, cover test,
      and ocular movement examinations. Uncorrected VA and best-corrected VA (BCVA)
      were measured with a logarithm of the minimum angle of resolution (logMAR) chart.
      Cycloplegic autorefraction was performed after administration of 1.0%
      cyclopentolate and Mydrin-P. Strabismus was defined as heterotropia at near or
      distance fixation. Amblyopia was defined as BCVA <= 0.1 logMAR units in one or
      both eyes, without ocular pathology in either eye. RESULTS: Of the 2363 eligible
      students, 2260 (95.6%) completed all examinations. The mean age of the students
      was 12.4 +/- 0.6 years. Amblyopia was present in 52 students (2.5%), of whom 33
      (63.5%) had unilateral and 19 (36.6%) had bilateral amblyopia. Of those with
      unilateral amblyopia, 18 (54.5 %) had anisometropia and 7 (21.2%) had strabismus.
      Of those with bilateral amblyopia, 6 (31.6%) had significant refractive error.
      Strabismus was present in 108 students (5.0%), of whom 2 (1.9%) had esotropia,
      102 (94.4%) had exotropia, 3 (2.8%) had vertical strabismus, and 1 (0.9%) had
      microstrabismus. Of the 108 students with strabismus, 9 (8.3%) had amblyopia.
      CONCLUSION: The cross-sectional ACES which examined the prevalence of amblyopia
      and strabismus in 7th-grade students in central China revealed the prevalence of
      strabismus, particularly the proportion of exotropia, to be higher than
      previously reported.

PMID- 24742060
TI  - School-entry vision screening in the United Kingdom: practical aspects and
      outcomes.
AB  - PURPOSE: To describe and assess an orthoptist-led vision screening service for
      school-entry (reception class) children, and report outcomes from one healthcare
      trust in the UK. METHODS: A total of 3721 children (aged 4-5 years) in reception
      class primary school (155 state, 3 private) underwent orthoptist-conducted vision
      screening. Children who failed to meet the screening criteria were referred to
      hospital-based eye services for re-testing and final diagnosis. RESULTS: The
      screening take-up rate was 96.41%; the remaining 3.59% refused/failed to consent
      to screening. The screening capture rate of participating children was 99.7%. A
      total of 11.14% of screened children failed to meet the screening criteria and
      were referred elsewhere; no abnormalities were found in 14% (false referral rate)
      of these children. Of the referred children, 53% had refractive errors requiring
      glasses and 42% had squints. The estimated percentages of common visual problems
      in screened children were 9.15% for refractive error and 3.81% for squint.
      CONCLUSION: An orthoptist-led, time-of-school-entry vision screening service is
      ideal for successful childhood vision screening and is, thus, a valuable source
      of information regarding the prevalence of common visual problems among children.

PMID- 24742061
TI  - Rate of diabetic vitrectomy in a defined geographical part of North East England.
AB  - PURPOSE: To assess the yearly incidence of vitrectomy for proliferative diabetic
      retinopathy (PDR) over an 11-year period, in a geographically defined part of
      North East England. The time period covered the introduction of diabetic
      retinopathy screening. METHODS: All patients undergoing vitrectomy for diabetic
      retinopathy in the Sunderland and South Tyneside area were recorded from 2000 to
      2010. Incidence rates of vitrectomy specifically for the complications of PDR for
      the observed diabetic population, the estimated diabetic population and the
      population with known PDR were calculated. RESULTS: There was a gradual and
      significant decline in the vitrectomy rate from 157 (95% confidence interval, CI,
      135-187) to 103 (95% CI 98-109) per 100,000 of the observed diabetic population
      in 2000 and 2010 respectively. The rate in the estimated diabetic population
      showed no significant change at 68 (95% CI 48-87) in 2002 and 77 (95% CI 55-103)
      in 2010. The rate in the PDR population, which comprised 2.4% of the known
      diabetic population in 2002 and 1.8% in 2010, declined significantly from 7.7% in
      2002 to 5.7% in 2010. CONCLUSION: This study evaluated vitrectomy rates for PDR
      in an area of North East England. There were apparent declining rates of
      vitrectomy for PDR following the introduction of diabetic retinopathy screening
      but these have to be interpreted in the light of several confounding factors.

PMID- 24742062
TI  - Invasive potential of cattle fever ticks in the southern United States.
AB  - ABSTRACT' BACKGROUND: For >100 years cattle production in the southern United
      States has been threatened by cattle fever. It is caused by an invasive parasite
      vector complex that includes the protozoan hemoparasites Babesia bovis and B.
      bigemina, which are transmitted among domestic cattle via Rhipicephalus tick
      vectors of the subgenus Boophilus. In 1906 an eradication effort was started and
      by 1943 Boophilus ticks had been confined to a narrow tick eradication quarantine
      area (TEQA) along the Texas-Mexico border. However, a dramatic increase in tick
      infestations in areas outside the TEQA over the last decade suggests these tick
      vectors may be poised to re-invade the southern United States. We investigated
      historical and potential future distributions of climatic habitats of cattle
      fever ticks to assess the potential for a range expansion. METHODS: We built
      robust spatial predictions of habitat suitability for the vector species
      Rhipicephalus (Boophilus) microplus and R. (B.) annulatus across the southern
      United States for three time periods: 1906, present day (2012), and 2050. We used
      analysis of molecular variance (AMOVA) to identify persistent tick occurrences
      and analysis of bias in the climate proximate to these occurrences to identify
      key environmental parameters associated with the ecology of both species. We then
      used ecological niche modeling algorithms GARP and Maxent to construct models
      that related known occurrences of ticks in the TEQA during 2001-2011 with
      geospatial data layers that summarized important climate parameters at all three
      time periods. RESULTS: We identified persistent tick infestations and specific
      climate parameters that appear to be drivers of ecological niches of the two tick
      species. Spatial models projected onto climate data representative of climate in
      1906 reproduced historical pre-eradication tick distributions. Present-day
      predictions, although constrained to areas near the TEQA, extrapolated well onto
      climate projections for 2050. CONCLUSIONS: Our models indicate the potential for
      range expansion of climate suitable for survival of R. microplus and R. annulatus
      in the southern United States by mid-century, which increases the risk of
      reintroduction of these ticks and cattle tick fever into major cattle producing
      areas.

PMID- 24742063
TI  - Second primary cancer risk - the impact of applying different definitions of
      multiple primaries: results from a retrospective population-based cancer registry
      study.
AB  - BACKGROUND: There is evidence that cancer survivors are at increased risk of
      second primary cancers. Changes in the prevalence of risk factors and diagnostic
      techniques may have affected more recent risks. METHODS: We examined the
      incidence of second primary cancer among adults in the West of Scotland, UK,
      diagnosed with cancer between 2000 and 2004 (n = 57,393). We used National Cancer
      Institute Surveillance Epidemiology and End Results and International Agency for
      Research on Cancer definitions of multiple primary cancers and estimated
      indirectly standardised incidence ratios (SIR) with 95% confidence intervals
      (CI). RESULTS: There was a high incidence of cancer during the first 60 days
      following diagnosis (SIR = 2.36, 95% CI = 2.12 to 2.63). When this period was
      excluded the risk was not raised, but it was high for some patient groups; in
      particular women aged <50 years with breast cancer (SIR = 2.13, 95% CI = 1.58 to
      2.78), patients with bladder (SIR = 1.41, 95% CI = 1.19 to 1.67) and head & neck
      (SIR = 1.93, 95% CI = 1.67 to 2.21) cancer. Head & neck cancer patients had
      increased risks of lung cancer (SIR = 3.75, 95% CI = 3.01 to 4.62), oesophageal
      (SIR = 4.62, 95% CI = 2.73 to 7.29) and other head & neck tumours (SIR = 6.10,
      95% CI = 4.17 to 8.61). Patients with bladder cancer had raised risks of lung
      (SIR = 2.18, 95% CI = 1.62 to 2.88) and prostate (SIR = 2.41, 95% CI = 1.72 to
      3.30) cancer. CONCLUSIONS: Relative risks of second primary cancers may be
      smaller than previously reported. Premenopausal women with breast cancer and
      patients with malignant melanomas, bladder and head & neck cancers may benefit
      from increased surveillance and advice to avoid known risk factors.

PMID- 24742064
TI  - BMI, physical inactivity, cigarette and alcohol consumption in female nursing
      students: a 5-year comparison.
AB  - BACKGROUND: Nursing staff are often involved in counseling patients with regard
      to health behavior. Although care promoting healthy lifestyle choices is included
      in the curriculum of nursing students in Germany, several studies of nursing
      students have reported a high prevalence of unhealthy behavior. This paper
      focuses on the behavior of female nursing students with regard to body mass index
      (BMI), physical activity, and cigarette and alcohol consumption. It describes
      trends through the comparison of results from 2008 and 2013. METHODS: Data was
      collected in two waves at a regional medical training college. First, 301 nursing
      students were asked to fill out a 12 page questionnaire on health behavior in
      2008. The questioning was repeated in 2013 with 316 participating nursing
      students using the previous questionnaire. RESULTS: 259 female nursing students
      completed the questionnaire in 2013. 31.6% of them were either overweight or
      obese, 28.5% exercised less than once a week, 42.9% smoked between 10 and 20
      cigarettes a day and 72.6% drank alcohol, wherefrom 19.7% consumed alcohol in
      risky quantities. In comparison to the data of 266 female nursing students from
      2008, there were significant differences in the BMI and alcohol consumption: The
      percentage of overweight and obese students and the percentage of alcohol
      consumers at risk increased significantly. CONCLUSIONS: Health behavior of female
      nursing students is often inadequate especially in regard to weight and cigarette
      and alcohol consumption. Strategies are required to promote healthy lifestyle
      choices.

PMID- 24742065
TI  - Combining test statistics and models in bootstrapped model rejection: it is a
      balancing act.
AB  - BACKGROUND: Model rejections lie at the heart of systems biology, since they
      provide conclusive statements: that the corresponding mechanistic assumptions do
      not serve as valid explanations for the experimental data. Rejections are usually
      done using e.g. the chi-square test (chi2) or the Durbin-Watson test (DW).
      Analytical formulas for the corresponding distributions rely on assumptions that
      typically are not fulfilled. This problem is partly alleviated by the usage of
      bootstrapping, a computationally heavy approach to calculate an empirical
      distribution. Bootstrapping also allows for a natural extension to estimation of
      joint distributions, but this feature has so far been little exploited. RESULTS:
      We herein show that simplistic combinations of bootstrapped tests, like the max
      or min of the individual p-values, give inconsistent, i.e. overly conservative or
      liberal, results. A new two-dimensional (2D) approach based on parametric
      bootstrapping, on the other hand, is found both consistent and with a higher
      power than the individual tests, when tested on static and dynamic examples where
      the truth is known. In the same examples, the most superior test is a 2D
      chi2vschi2, where the second chi2-value comes from an additional help model, and
      its ability to describe bootstraps from the tested model. This superiority is
      lost if the help model is too simple, or too flexible. If a useful help model is
      found, the most powerful approach is the bootstrapped log-likelihood ratio (LHR).
      We show that this is because the LHR is one-dimensional, because the second
      dimension comes at a cost, and because LHR has retained most of the crucial
      information in the 2D distribution. These approaches statistically resolve a
      previously published rejection example for the first time. CONCLUSIONS: We have
      shown how to, and how not to, combine tests in a bootstrap setting, when the
      combination is advantageous, and when it is advantageous to include a second
      model. These results also provide a deeper insight into the original motivation
      for formulating the LHR, for the more general setting of nonlinear and non-nested
      models. These insights are valuable in cases when accuracy and power, rather than
      computational speed, are prioritized.

PMID- 24742066
TI  - A turn on and a turn off: BLT1 and BLT2 mechanisms in the lung.
AB  - Leukotriene B4 (LTB4), a potent lipid mediator of inflammation derived from
      arachidonic acid through the action of 5-lipoxygenase, has been implicated in the
      pathophysiology of several inflammatory diseases, including asthma and chronic
      obstructive pulmonary disease. A high-affinity LTB4 receptor BLT1 has been shown
      to exert proinflammatory roles. A cyclooxygenase metabolite, 12(S)
      hydroxyheptadeca-5Z, 8E, 10E-trienoic acid (12-HHT), is an endogenous ligand for
      BLT2, a low-affinity LTB4 receptor. The recent study indicated that BLT2 has a
      protective role in allergic airway inflammation, suggesting different functions
      between BLT1 and BLT2 in the pathogenesis of asthma. Selective BLT1 antagonists
      may have a potential therapeutic application in patients with asthma, and BLT2
      may represent a novel therapeutic target for lung diseases. 

PMID- 24742067
TI  - Glutamine attenuates the inhibitory effect of methotrexate on TLR signaling
      during intestinal chemotherapy-induced mucositis in a rat.
AB  - Toll-like receptor 4 (TLR-4) is crucial in maintaining intestinal epithelial
      homeostasis, participates in a vigorous signaling process and heightens
      inflammatory cytokine output. The objective of this study was to determine the
      effects of glutamine (GLN) on TLR-4 signaling in intestinal mucosa during
      methotrexate (MTX)-induced mucositis in a rat. Male Sprague-Dawley rats were
      randomly assigned to one of four experimental groups of 8 rats each: 1) control
      rats; 2) CONTR-GLN animals were treated with oral glutamine given in drinking
      water (2%) 48 hours before and 72 hours following vehicle injection; 3) MTX-rats
      were treated with a single IP injection of MTX (20 mg/kg); and 4) MTX-GLN rats
      were pre-treated with oral glutamine similar to group B, 48 hours before and 72
      hours after MTX injection. Intestinal mucosal damage, mucosal structural changes,
      enterocyte proliferation and enterocyte apoptosis were determined 72 hours
      following MTX injection. The expression of TLR-4, MyD88 and TRAF6 in the
      intestinal mucosa was determined using real time PCR, Western blot and
      immunohistochemistry. MTX-GLN rats demonstrated a greater jejunal and ileal
      mucosal weight and mucosal DNA, greater villus height in ileum and crypt depth
      and index of proliferation in jejunum and ileum, compared to MTX animals. The
      expression of TLR-4 and MyD88 mRNA and protein in the mucosa was significantly
      lower in MTX rats versus controls animals. The administration of GLN increased
      significantly the expression of TLR-4 and MyD88 (vs the MTX group). In
      conclusion, treatment with glutamine was associated with up-regulation of TLR-4
      and MyD88 expression and a concomitant decrease in intestinal mucosal injury
      caused by MTX-induced mucositis in a rat. 

PMID- 24742068
TI  - Quality of life in children and adolescents with Osteogenesis Imperfecta: a
      qualitative interview based study.
AB  - BACKGROUND: Osteogenesis Imperfecta (OI) is a disease with varying severity
      affecting physical, social and emotional well-being of the child and their
      family. There is no existing evidence on how the OI population regard their
      quality of life (QoL). The main aim of this study was to determine how OI impacts
      on the quality of life and well-being of children and their family. It is the
      first stage of a larger project to develop a disease specific quality of life
      measure for children with OI. METHODS: Purposive sampling was used to cover the
      diversity of the OI population. Twenty-five qualitative interviews were
      undertaken with children (n = 10), parents (n = 10) and health professionals (n =
      5). Interviews were digitally recorded and transcribed verbatim. Significant
      themes were identified, extracted and organised, undergoing framework analysis.
      RESULTS: Six main themes were identified; being safe and careful, reduced
      function, pain, fear, isolation, independence. There was a large amount of
      agreement between the three groups of interviewees, although discrepancies did
      occur between parents and children, with regard to the themes independence and
      fear. CONCLUSIONS: This data presents the first step in developing items for a
      disease specific QoL measure for children with OI. Several of the themes
      uncovered showed similarity to other QoL measures, but the addition of being safe
      and careful, particularly in relation to fractures, demonstrated the need for a
      disease specific measure for children with OI.

PMID- 24742070
TI  - The German version of the Generalized Pathological Internet Use Scale 2: a
      validation study.
AB  - The Generalized Pathological Internet Use Scale (GPIUS2) assesses cognitive
      behavioral aspects of problematic Internet use. To date, the 15-item scale has
      only been available in English, and the aim of this study was to translate and
      validate a German version. An online sample (ON, n=1,041, age 24.2+/-7.2 years,
      46.7% men) completed an Internet version of the translated GPIUS2, and a student
      sample (OF, n=841, age 23.5+/-3.0 years, 46.8% men) filled in a pencil and paper
      version. A third sample of 108 students (21.5+/-2.0 years, 25.7% men) completed
      the questionnaire twice to determine the 14-day retest reliability. Participants
      also answered questions regarding their Internet use habits (OF, ON) and
      depression, loneliness, and social anxiety (ON). The internal consistencies were
      alpha=0.91 (ON) and alpha=0.86 (OF). Item-whole correlations ranged from r=0.53
      to r=0.69 (ON) and from r=0.39 to r=0.63 (OF). The 2 week retest reliability was
      rtt=0.85. Confirmatory factor analyses found a satisfactory fit for the factorial
      model proposed by Caplan for the original version. The GPIUS2 score correlated
      moderately with time spent on the Internet for private purposes in a typical week
      (ON: r=0.40; OF: r=0.36). Loneliness, depression, and social anxiety explained
      46% of the variance in GPIUS2 scores. The German version of the GPIUS2 has good
      psychometric properties in a pencil and paper version as well as in a web-based
      format, and the observations regarding loneliness, depression, and social anxiety
      support the underlying model.

PMID- 24742071
TI  - Fusarium verticillioides SGE1 is required for full virulence and regulates
      expression of protein effector and secondary metabolite biosynthetic genes.
AB  - The transition from one lifestyle to another in some fungi is initiated by a
      single orthologous gene, SGE1, that regulates markedly different genes in
      different fungi. Despite these differences, many of the regulated genes encode
      effector proteins or proteins involved in the synthesis of secondary metabolites
      (SM), both of which can contribute to pathogenicity. Fusarium verticillioides is
      both an endophyte and a pathogen of maize and can grow as a saprophyte on dead
      plant material. During growth on live maize plants, the fungus can synthesize a
      number of toxic SM, including fumonisins, fusarins, and fusaric acid, that can
      contaminate kernels and kernel-based food and feed. In this study, the role of F.
      verticillioides SGE1 in pathogenicity and secondary metabolism was examined by
      gene deletion analysis and transcriptomics. SGE1 is not required for vegetative
      growth or conidiation but is required for wild-type pathogenicity and affects
      synthesis of multiple SM, including fumonisins and fusarins. Induced expression
      of SGE1 enhanced or reduced expression of hundreds of genes, including numerous
      putative effector genes that could contribute to growth in planta; genes encoding
      cell surface proteins; gene clusters required for synthesis of fusarins,
      bikaverin, and an unknown metabolite; as well as the gene encoding the fumonisin
      cluster transcriptional activator. Together, our results indicate that SGE1 has a
      role in global regulation of transcription in F. verticillioides that impacts but
      is not absolutely required for secondary metabolism and pathogenicity on maize. 

PMID- 24742072
TI  - Three-dimensional modeling and diversity analysis reveals distinct AVR
      recognition sites and evolutionary pathways in wild and domesticated wheat Pm3 R
      genes.
AB  - The Pm3 gene confers resistance against wheat powdery mildew. Studies of Pm3
      diversity have shown that Pm3 alleles isolated from southern populations of wild
      emmer wheat located in Lebanon, Jordan, Israel, and Syria are more diverse and
      more distant from bread wheat alleles than alleles from the northern wild wheat
      populations located in Turkey, Iran, and Iraq. Therefore, southern populations
      from Israel were studied extensively to reveal novel Pm3 alleles that are absent
      from the cultivated gene pool. Candidate Pm3 genes were isolated via a polymerase
      chain reaction cloning approach. Known and newly identified Pm3 genes were
      subjected to variation analysis and polymorphic amino acid residues were
      superimposed on a three-dimensional (3D) model of PM3. The region of highest
      interspecies diversity between Triticum aestivum and T. dicoccoides lies in
      leucine-rich repeats (LRR) 19 to 24, whereas most intraspecies diversity in T.
      aestivum is located in LRR 25 to 28. Interestingly, these two regions are
      separated by one large LRR whose propensity for flexibility facilitates the
      conformation of the PM3 LRR domain into two differently structured models. The
      combination of evolutionary and protein 3D structure analysis revealed that Pm3
      genes in wild and domesticated wheat show different evolutionary histories which
      might have been triggered through different interactions with the powdery mildew
      pathogen. 

PMID- 24742073
TI  - Pseudomonas protegens Pf-5 causes discoloration and pitting of mushroom caps due
      to the production of antifungal metabolites.
AB  - Bacteria in the diverse Pseudomonas fluorescens group include rhizosphere
      inhabitants known for their antifungal metabolite production and biological
      control of plant disease, such as Pseudomonas protegens Pf-5, and mushroom
      pathogens, such as Pseudomonas tolaasii. Here, we report that strain Pf-5 causes
      brown, sunken lesions on peeled caps of the button mushroom (Agaricus bisporus)
      that resemble brown blotch symptoms caused by P. tolaasii. Strain Pf-5 produces
      six known antifungal metabolites under the control of the GacS/GacA signal
      transduction system. A gacA mutant produces none of these metabolites and did not
      cause lesions on mushroom caps. Mutants deficient in the biosynthesis of the
      antifungal metabolites 2,4-diacetylphloroglucinol and pyoluteorin caused less
      severe symptoms than wild-type Pf-5 on peeled mushroom caps, whereas mutants
      deficient in the production of lipopeptide orfamide A caused similar symptoms to
      wild-type Pf-5. Purified pyoluteorin and 2,4-diacetylphloroglucinol mimicked the
      symptoms caused by Pf-5. Both compounds were isolated from mushroom tissue
      inoculated with Pf-5, providing direct evidence for their in situ production by
      the bacterium. Although the lipopeptide tolaasin is responsible for brown blotch
      of mushroom caused by P. tolaasii, P. protegens Pf-5 caused brown blotch-like
      symptoms on peeled mushroom caps through a lipopeptide-independent mechanism
      involving the production of 2,4-diacetylphloroglucinol and pyoluteorin. 

PMID- 24742074
TI  - Stepwise arms race between AvrPik and Pik alleles in the rice blast pathosystem.
AB  - A stepwise mutation that occurred in both pathogens and their respective hosts
      has played a seminal role in the co-evolutionary arms race evolution in diverse
      pathosystems. The process driven by rice blast AvrPik and Pik alleles was
      investigated through population genetic and evolutionary approaches. The genetic
      diversity of the non-signal domain of AvrPik was higher than that in its signal
      peptide domain. Positive selection for particular AvrPik alleles in the
      northeastern region of China was stronger than in the south. The perfect
      relationship between the functional lineages and AvrPik allele-specific
      pathotypes was established by ruling out the nonfunctional lineages derived from
      additional copies. Only four alleles conditioning stepwise pathotypes were
      detected in natural populations, which were likely created by only one
      evolutionary pathway with three recognizable mutation steps. Two non-stepwise
      pathotypes were determined by two blocks in a network constructed by all 16
      possible alleles, indicating that a natural evolution process can be artificially
      changed by a combination of specific single-nucleotide polymorphisms. Assuming
      that AvrPik evolution has been largely driven by host selection, the co
      evolutionary stepwise relationships between AvrPik and Pik was established. The
      experimental validation of stepwise mutation is required for the development of
      sustainable management strategies against plant disease. 

PMID- 24742075
TI  - Predictive processing, perceptual presence, and sensorimotor theory.
AB  - Mastery of sensorimotor contingencies can be viewed as attunement to
      potentialities. In our view, these potentialities have wider application than
      recognized in Seth's account of sensory presence, and should pertain to all of
      sensory experience. Instead of appealing only to a notion of counterfactual
      richness, we propose that the degree of sensory presence can be further specified
      in terms of bodiliness, insubordinateness, and grabbiness. While PPSMC can
      provide a possible implementation of a sensorimotor account of synesthesia, we
      suggest it should be rid of its representationalist interpretation.

PMID- 24742076
TI  - Photonic-plasmonic coupling of GaAs single nanowires to optical nanoantennas.
AB  - We successfully demonstrate the plasmonic coupling between metal nanoantennas and
      individual GaAs nanowires (NWs). In particular, by using dark-field scattering
      and second harmonic excitation spectroscopy in partnership with analytical and
      full-vector FDTD modeling, we demonstrate controlled electromagnetic coupling
      between individual NWs and plasmonic nanoantennas with gap sizes varied between
      90 and 500 nm. The significant electric field enhancement values (up to 20*)
      achieved inside the NW-nanoantennas gap regions allowed us to tailor the
      nonlinear optical response of NWs by engineering the plasmonic near-field
      coupling regime. These findings represent an initial step toward the development
      of coupled metal-semiconductor resonant nanostructures for the realization of
      next generation solar cells, detectors, and nonlinear optical devices with
      reduced footprints and energy consumption. 

PMID- 24742077
TI  - Measuring edge importance: a quantitative analysis of the stochastic shielding
      approximation for random processes on graphs.
AB  - Mathematical models of cellular physiological mechanisms often involve random
      walks on graphs representing transitions within networks of functional states.
      Schmandt and Galan recently introduced a novel stochastic shielding approximation
      as a fast, accurate method for generating approximate sample paths from a finite
      state Markov process in which only a subset of states are observable. For
      example, in ion-channel models, such as the Hodgkin-Huxley or other conductance
      based neural models, a nerve cell has a population of ion channels whose states
      comprise the nodes of a graph, only some of which allow a transmembrane current
      to pass. The stochastic shielding approximation consists of neglecting
      fluctuations in the dynamics associated with edges in the graph not directly
      affecting the observable states. We consider the problem of finding the optimal
      complexity reducing mapping from a stochastic process on a graph to an
      approximate process on a smaller sample space, as determined by the choice of a
      particular linear measurement functional on the graph. The partitioning of ion
      channel states into conducting versus nonconducting states provides a case in
      point. In addition to establishing that Schmandt and Galan's approximation is in
      fact optimal in a specific sense, we use recent results from random matrix theory
      to provide heuristic error estimates for the accuracy of the stochastic shielding
      approximation for an ensemble of random graphs. Moreover, we provide a novel
      quantitative measure of the contribution of individual transitions within the
      reaction graph to the accuracy of the approximate process. 

PMID- 24742078
TI  - Development of the Sexual Five-Facet Mindfulness Questionnaire (FFMQ-S):
      Validation Among a Community Sample of French-Speaking Women.
AB  - It has been recently demonstrated that mindfulness-based intervention may be
      particularly suitable for addressing sexual difficulties in women. Although the
      Five-Facet Mindfulness Questionnaire (FFMQ) is currently one of the most widely
      used scales to assess mindfulness, no adaptation and validation of the FFMQ to
      measure female sexual functioning has been published. The main aim of this study
      was to develop and validate a sexual version of the Five Facets Mindfulness
      Questionnaire (FFMQ-S) to specifically measure mindfulness in the context of
      sexual encounters. A total of 251 healthy, French-speaking female volunteers were
      administered the FFMQ-S, the original FFMQ, and the Female Sexual Distress Scale
      (FSDS-R). Confirmatory factor analyses indicated that the FFMQ-S exhibits a five
      factor model, as implied by the original FFMQ. Good scale reliability was
      observed. The FFMQ-S showed significant correlations with the FSDS-R and the
      usual FFMQ. Scores on the FFMQ-S correlated significantly more negatively with
      the total FSDS-R score than with the total score of the original version of the
      FFMQ. These findings clearly support the relevance of developing a version of the
      FFMQ tailored to sexual functioning. 

PMID- 24742079
TI  - Correlation between depression, anxiety, and polymorphonuclear cells' resilience
      in ulcerative colitis: the mediating role of heat shock protein 70.
AB  - BACKGROUND: To investigate whether anxiety and depression levels are associated
      with Heat Shock Protein 70 (HSP70) induction in the colon of patients with
      ulcerative colitis (UC). METHODS: The design was cross-sectional. Clinical
      activity was assessed by the Rachmilewitz Index (CAI). Three psychometric
      questionnaires were used: Zung Depression Rating Scale (ZDRS), Spielberg State
      Trait Anxiety Inventory (STAI), Hospital Anxiety and Depression Scale (HADS).
      Colon biopsies were obtained from each affected anatomical site. Severity of
      inflammation was assessed by eosin/hematoxylin. Constitutive (HSP70c) and
      inducible (HSP70i) HSP70 expression were immunohistochemically studied. RESULTS:
      29 UC patients were enrolled (69% men). Mean age was 46.5 years (SD: 19.5).
      Inflammation severity was moderate in 17 patients, severe in 6, and mild in 6.
      The mean number of years since diagnosis was 7.9 (SD: 6.5). The mean CAI was 6.4
      (SD: 3.1). In active UC, there was downregulation of HSP70c in inflamed
      epithelium, without significant HSP70 induction. In 22/29 cases of active
      cryptitis, polymorphonuclear cells (PMN) clearly expressed HSP70i, with weak,
      focal positivity in the other 7 cases. Except for the hospital anxiety scale,
      scores in all psychometric tools were higher in patients with strong HSP70i
      immunoreactivity in the PMN. Logistic regression showed a strong positive
      relationship between HSP70i immunoreactivity in the PMN cells and scores in the
      trait anxiety, ZDRS, and hospital depression scales, (Odds ratios 1.3, 1.3, and
      1.5; P = 0.018, 0.023, and 0.038; Wald test, 5.6, 5.2, and 4.3 respectively) and
      a weaker but significant positive correlation with the CAI (Odds ratio 1.654; P =
      0.049; Wald test 3.858). CONCLUSION: HSP70 is induced in PMN cells of UC patients
      and its induction correlates with depression and anxiety levels.

PMID- 24742080
TI  - Identification of a strawberry flavor gene candidate using an integrated genetic
      genomic-analytical chemistry approach.
AB  - BACKGROUND: There is interest in improving the flavor of commercial strawberry
      (Fragaria * ananassa) varieties. Fruit flavor is shaped by combinations of
      sugars, acids and volatile compounds. Many efforts seek to use genomics-based
      strategies to identify genes controlling flavor, and then designing durable
      molecular markers to follow these genes in breeding populations. In this report,
      fruit from two cultivars, varying for presence-absence of volatile compounds,
      along with segregating progeny, were analyzed using GC/MS and RNAseq. Expression
      data were bulked in silico according to presence/absence of a given volatile
      compound, in this case gamma-decalactone, a compound conferring a peach flavor
      note to fruits. RESULTS: Computationally sorting reads in segregating progeny
      based on gamma-decalactone presence eliminated transcripts not directly relevant
      to the volatile, revealing transcripts possibly imparting quantitative
      contributions. One candidate encodes an omega-6 fatty acid desaturase, an enzyme
      known to participate in lactone production in fungi, noted here as FaFAD1. This
      candidate was induced by ripening, was detected in certain harvests, and
      correlated with gamma-decalactone presence. The FaFAD1 gene is present in every
      genotype where gamma-decalactone has been detected, and it was invariably missing
      in non-producers. A functional, PCR-based molecular marker was developed that
      cosegregates with the phenotype in F1 and BC1 populations, as well as in many
      other cultivars and wild Fragaria accessions. CONCLUSIONS: Genetic, genomic and
      analytical chemistry techniques were combined to identify FaFAD1, a gene likely
      controlling a key flavor volatile in strawberry. The same data may now be re
      sorted based on presence/absence of any other volatile to identify other flavor
      affecting candidates, leading to rapid generation of gene-specific markers.

PMID- 24742082
TI  - Anorectal conditions: foreward.

PMID- 24742081
TI  - Solvent-dependent divergent functions of Sc(OTf)3 in stereoselective epoxide
      opening spiroketalizations.
AB  - A stereocontrolled synthesis of benzannulated spiroketals has been developed
      using solvent-dependent Sc(OTf)3-mediated spirocyclizations of exo-glycal
      epoxides having alcohol side chains. In THF, the reaction proceeds via Lewis acid
      catalysis under kinetic control with inversion of configuration at the anomeric
      carbon. In contrast, in CH2Cl2, Bronsted acid catalysis under thermodynamic
      control leads to retention of configuration. The reactions accommodate a variety
      of aryl substituents and ring sizes and provide stereochemically diverse
      spiroketals. 

PMID- 24742083
TI  - Anorectal conditions: hemorrhoids.
AB  - Hemorrhoids are engorged fibrovascular cushions lining the anal canal.
      Constipation, increased intra-abdominal pressure, and prolonged straining
      predispose to hemorrhoids. Approximately 1 in 20 Americans and almost one-half of
      individuals older than 50 years experience symptomatic hemorrhoids. Bright red,
      painless rectal bleeding during defecation is the most common presentation. Even
      if hemorrhoids are seen on examination, patients with rectal bleeding who are at
      risk of colorectal cancer (eg, adults older than 50 years) should still undergo
      colonoscopy to exclude cancer as the etiology. Nonsurgical treatment for
      nonthrombosed hemorrhoids includes increased fiber intake, sitz baths, and drugs.
      If nonsurgical management is unsuccessful, rubber band ligation is the most
      effective office-based procedure for grades I, II, and III hemorrhoids. Surgical
      hemorrhoidectomy is indicated after failure of nonsurgical management and office
      based procedures and also as initial management for grades III and IV
      hemorrhoids. Several different procedures can be used. For acutely thrombosed
      external hemorrhoids, excision and evacuation of the clot, ideally within 72
      hours of symptom onset, is the optimal management. Prolapsed and strangulated
      hemorrhoids are best managed with stool softeners, analgesics, rest, warm soaks,
      and ice packs until recovery; residual hemorrhoids are banded or excised later. 

PMID- 24742084
TI  - Anorectal conditions: anal fissure and anorectal fistula.
AB  - Anal fissures are linear splits in the anal mucosa. Acute fissures typically
      resolve within a few weeks; chronic fissures persist longer than 8 to 12 weeks.
      Most fissures are posterior and midline and are related to constipation or anal
      trauma. Painful defecation and rectal bleeding are common symptoms. The diagnosis
      typically is clinical. High-fiber diet, stool softeners, and medicated ointments
      relieve symptoms and speed healing of acute fissures but offer limited benefit in
      chronic fissures. Lateral internal sphincterotomy is the surgical management of
      choice for chronic and refractory acute fissures. Anorectal fistula is an
      abnormal tract connecting the anorectal mucosa to the exterior skin. Fistulas
      typically develop after rupture or drainage of a perianal abscess. Fistulas are
      classified as simple or complex; low or high; and intersphincteric,
      transsphincteric, suprasphincteric, or extrasphincteric. Inspection of the
      perianal area identifies the skin opening, and anoscopy visualizes internal
      openings. The goal of management is to obliterate the tract and openings with
      negligible sphincter disruption to minimize incontinence. Fistulotomy is
      effective for simple fistulas; patients with complex fistulas may require
      fistulectomy. Other procedures that are used include injection of fibrin glue or
      insertion of a bioprosthetic plug into the fistula opening. 

PMID- 24742085
TI  - Anorectal conditions: rectal prolapse.
AB  - Rectal prolapse, the protrusion of the layers of the rectal wall through the anal
      canal, may be partial (mucosal) or complete (full thickness). Although prolapse
      is most common among older women, it affects individuals of all ages, including
      children. Associated fecal incontinence and constipation are typical. Urinary
      incontinence and uterovaginal/bladder prolapse also may coexist. Some patients
      may have rectal ulcers. Diagnosis is predominantly clinical; visualization of the
      prolapse may require the patient to strain while sitting or squatting. Imaging
      studies, including fluoroscopic or dynamic magnetic resonance defecography, can
      confirm the prolapse if the diagnosis is uncertain, and endoscopy can aid in
      detecting other colonic/extracolonic pathology. Nonsurgical management (eg,
      increased fiber intake, fiber supplements, biofeedback) often is therapeutic in
      minor (first- or second-degree) mucosal prolapse and can help alleviate
      constipation and incontinence before and after surgery for patients with full
      thickness prolapse. However, for full-thickness prolapse, transabdominal
      procedures are the most effective management and are favored for healthy
      patients, irrespective of age. Perineal procedures (eg, rubber band ligation,
      mucosal excision) can be used for patients with full-thickness prolapse who are
      not candidates for transabdominal surgery and for those with second- and third
      degree mucosal prolapse. 

PMID- 24742086
TI  - Anorectal conditions: fecal incontinence.
AB  - Although fecal incontinence occurs in all age groups, it is more common among
      older adults, especially nursing home residents, and it is more common among
      women than men. It often is associated with urinary incontinence. Etiologies are
      broadly categorized to include anatomic/physiologic changes due to trauma,
      surgery, vaginal deliveries, radiation, or disease states; neurologic disorders;
      drugs; and functional impairments. Evaluation is aimed at identifying etiologies,
      and scoring systems can be used to estimate severity and monitor outcomes. The
      first step in treatment is managing possible etiologies and implementing
      conservative measures, including increasing dietary fiber intake, using
      antidiarrheal drugs, removing fecal impactions, and using biofeedback. If these
      measures fail to control incontinence, further testing can characterize specific
      defects. Tests include endorectal ultrasound, anorectal manometry, and pudendal
      nerve terminal motor latency. After the defect is characterized, management
      options include injecting biocompatible material to bulk up a rectal sphincter
      with a defined defect, suture repair of sphincter defects, transfer of gracilis
      or gluteal muscle to create a new sphincter, implanting an artificial sphincter
      or neurostimulator, creating an ostomy through which retrograde enemas can be
      administered, and colostomy to prevent feces from reaching the rectum. Anal plugs
      are a last resort. 

PMID- 24742087
TI  - The effect of intrapartum antibiotics on early-onset neonatal sepsis in Dhaka,
      Bangladesh: a propensity score matched analysis.
AB  - BACKGROUND: We estimate the effect of antibiotics given in the intrapartum period
      on early-onset neonatal sepsis in Dhaka, Bangladesh using propensity score
      techniques. METHODS: We followed 600 mother-newborn pairs as part of a cohort
      study at a maternity center in Dhaka. Some pregnant women received one dose of
      intravenous antibiotics during labor based on clinician discretion. Newborns were
      followed over the first seven days of life for early-onset neonatal sepsis
      defined by a modified version of the World Health Organization Young Infants
      Integrated Management of Childhood Illnesses criteria.Using propensity scores we
      matched women who received antibiotics with similar women who did not. A final
      logistic regression model predicting sepsis was run in the matched sample
      controlling for additional potential confounders. RESULTS: Of the 600 mother
      newborn pairs, 48 mothers (8.0%) received antibiotics during the intrapartum
      period. Seventy-seven newborns (12.8%) were classified with early-onset neonatal
      sepsis. Antibiotics appeared to be protective (odds ratio 0.381, 95% confidence
      interval 0.115-1.258), however this was not statistically significant. The
      results were similar after adjusting for prematurity, wealth status, and maternal
      colonization status (odds ratio 0.361, 95% confidence interval 0.106-1.225).
      CONCLUSIONS: Antibiotics administered during the intrapartum period may reduce
      the risk of early-onset neonatal sepsis in high neonatal mortality settings like
      Dhaka.

PMID- 24742088
TI  - Genotyping and subtyping Cryptosporidium parvum and Giardia duodenalis carried by
      flies on dairy farms in Henan, China.
AB  - BACKGROUND: Cryptosporidium and Giardia are important causes of diarrhea diseases
      in humans and animals worldwide, and both of them are transmitted by the fecal
      oral route, either by direct contact or by the ingestion of contaminated food or
      water. The role of flies in the mechanical transmission of Cryptosporidium and
      Giardia has been receiving increasing attention. To date, no information is
      available in China about the occurrence of Cryptosporidium and Giardia in flies.
      We here investigated Cryptosporidium and Giardia in flies on dairy farms in Henan
      Province, China, at the genotype and subtype levels. METHODS: Eight hundred flies
      were randomly collected from two dairy farms from July 2010 to September 2010 and
      were divided evenly into 40 batches. The fly samples were screened for the
      presence of Cryptosporidium and Giardia with nested PCR. Cryptosporidium was
      genotyped and subtyped by analyzing the DNA sequences of small subunit rRNA (SSU
      rRNA) and 60-kDa glycoprotein (gp60) genes, respectively. The identity of Giardia
      was determined by sequence analyzing of the triosephosphate isomerase (tpi),
      glutamate dehydrogenase (gdh), and beta-giardin (bg) genes. RESULTS: Forty
      batches of flies had 10% of contamination with Cryptosporidium or Giardia, with a
      mixed infection of the two parasites in one batch of flies. The Cryptosporidium
      isolates were identified as C. parvum at the SSU rRNA locus, and all belonged to
      subtype IIdA19G1 at the gp60 locus. The Giardia isolates were all identified as
      assemblage E of G. duodenalis at the tpi, gdh, and bg loci. One novel subtype of
      assemblage E was identified based on the gdh and bg loci. CONCLUSIONS: This is
      the first molecular study of Cryptosporidium and Giardia in flies identified at
      both genotype and subtype levels. SSU rRNA and gp60 sequences of C. parvum in
      flies was 100% homologous with those derived from humans, suggesting flies act as
      an epidemiological vector of zoonotic cryptosporidiosis. The variable PCR
      efficiencies observed in the analysis of Giardia at different loci suggest that
      we should use the multilocus genotyping tool in future studies to increase the
      detection rate, and importantly, to obtain more complete genetic information on
      Giardia isolates.

PMID- 24742089
TI  - Protein chaperones: a composition of matter review (2008 - 2013).
AB  - INTRODUCTION: Heat shock proteins (Hsps) are proteins with important functions in
      regulating disease phenotypes. Historically, Hsp90 has first received recognition
      as a target in cancer, with consequent efforts extending its potential role to
      other diseases. Hsp70 has also attracted interest as a therapeutic target for its
      role as a co-chaperone to Hsp90 as well as its own anti-apoptotic roles. AREAS
      COVERED: Herein, patents from 2008 to 2013 are reviewed to identify those that
      disclose composition of matter claimed to inhibit Hsp90 or Hsp70. EXPERT OPINION:
      For Hsp90, there has been considerable creativity in the discovery of novel
      pharmacophores that fall outside the three initially discovered scaffolds (i.e.,
      ansamycins, resorcinols and purines). Nonetheless, much of the patent literature
      appears to build on previously reported structure activity relationship through
      slight modifications of Hsp90 inhibitor space by finding weaknesses in existing
      patents. The major goal of future development of Hsp90 inhibitors is not
      necessarily identifying better molecules but rather understanding how to
      rationally use these agents in the clinic. The development of Hsp70 inhibitors
      has lagged behind. It will require a more concerted effort from the drug
      discovery community in order to begin to realize the potential of this target.

PMID- 24742091
TI  - Do we develop public health leaders?- association between public health
      competencies and emotional intelligence: a cross-sectional study.
AB  - BACKGROUND: Professional development of public health leaders requires a form of
      instruction which is competency-based to help them develop the abilities to
      address complex and evolving demands of health care systems. Concurrently,
      emotional intelligence (EI) is a key to organisational success. Our aim was
      twofold: i) to assess the relationship between the level of self-assessed public
      health and EI competencies among Master of European Public Health (MEPH) students
      and graduates at Maastricht University, and; ii) to determine the relationship
      between different groups of public health competencies and specific EI skills.
      METHODS: A cross-sectional study was conducted including all recent MEPH
      graduates and students from 2009-2012, out of 67 eligible candidates N = 51 were
      contacted and N = 33 responded (11 males and 22 females; overall response:
      64.7%).Two validated tools were employed: i) public health competencies self
      assessment questionnaire, and; ii) Assessing Emotions Scale. RESULTS: Females
      scored higher than males in all seven domains of the self-assessed key public
      health competencies (NS) and emotional intelligence competences (P = 0.022).
      Overall, the mean value of public health competencies was the lowest in students
      with "staff" preferences and the highest among students with mixed job
      preferences (P < 0.001). There was evidence of a correlation between the overall
      public health competencies and the overall emotional intelligence competencies (r
      = 0.61, P < 0.001). CONCLUSIONS: The study shows a positive correlation between
      public health specific competencies and EI attributes. It can contribute to the
      improvement of the educational content of PH curricula by rising awareness
      through self-assessment and supporting the identification of further educational
      needs related to leadership.

PMID- 24742092
TI  - Fast Bayesian inference for gene regulatory networks using ScanBMA.
AB  - BACKGROUND: Genome-wide time-series data provide a rich set of information for
      discovering gene regulatory relationships. As genome-wide data for mammalian
      systems are being generated, it is critical to develop network inference methods
      that can handle tens of thousands of genes efficiently, provide a systematic
      framework for the integration of multiple data sources, and yield robust,
      accurate and compact gene-to-gene relationships. RESULTS: We developed and
      applied ScanBMA, a Bayesian inference method that incorporates external
      information to improve the accuracy of the inferred network. In particular, we
      developed a new strategy to efficiently search the model space, applied data
      transformations to reduce the effect of spurious relationships, and adopted the g
      prior to guide the search for candidate regulators. Our method is highly
      computationally efficient, thus addressing the scalability issue with network
      inference. The method is implemented as the ScanBMA function in the networkBMA
      Bioconductor software package. CONCLUSIONS: We compared ScanBMA to other popular
      methods using time series yeast data as well as time-series simulated data from
      the DREAM competition. We found that ScanBMA produced more compact networks with
      a greater proportion of true positives than the competing methods. Specifically,
      ScanBMA generally produced more favorable areas under the Receiver-Operating
      Characteristic and Precision-Recall curves than other regression-based methods
      and mutual-information based methods. In addition, ScanBMA is competitive with
      other network inference methods in terms of running time.

PMID- 24742093
TI  - Counterion effect on interfacial water at charged interfaces and its relevance to
      the Hofmeister series.
AB  - Specific counterion effects represented by Hofmeister series are important for a
      variety of phenomena such as protein precipitations, surface tensions of
      electrolytes solutions, phase transitions of surfactants, etc. We applied
      heterodyne-detected vibrational sum-frequency generation spectroscopy to study
      the counterion effect on the interfacial water at charged interfaces and
      discussed the observed effect with relevance to the Hofmeister series.
      Experiments were carried out for model systems of positively charged
      cetyltrimethylammonium monolayer/electrolyte solution interface and negatively
      charged dodecylsulfate monolayer/electrolyte interface. At the positively charged
      interface, the intensity of the OH band of the interfacial water decreases in the
      order of the Hofmeister series, suggesting that the adsorbability of halide
      anions onto the interface determines the Hofmeister order as previously proposed
      by Zhang and Cremer (Curr. Opin. Chem. Biol. 2006, 10, 658-663). At the
      negatively charged interfaces, on the other hand, the OH band intensity does not
      depend significantly on the countercation, whereas variation in the hydrogen-bond
      strength of the interfacial water is well correlated with the Hofmeister order of
      the cation effect. These results provide new insights into the molecular level
      mechanisms of anionic and cationic Hofmeister effects. 

PMID- 24742094
TI  - Radiation-induced malignant fibrous histiocytoma of the occipital: a case report.
AB  - Malignant fibrous histiocytoma (MFH) is a rare neoplasm exhibiting a propensity
      for aggressive clinical behavior. Effective treatment modality is surgical
      resection with wide margins, but its rate of recurrence and metastasis is still
      high. Early detection and complete excision of the tumor is necessary. A MFH of
      the occipital developed in a 51-year-old woman eight years after surgery and
      radiation for medulloblastoma of the cerebellar vermis. The secondary neoplasm
      arose at the site of tumor resection within the irradiated field, and was
      resected. The development of sarcomas is a recognized complication of radiation
      therapy. The final diagnosis after the operation was MFH. Radiation-induced
      sarcoma (RIS) is well known, but radiation-induced MFH is relatively rare in the
      head and neck region, especially in the occipital. The imaging findings are not
      diagnosis specific, but strict follow-up within the radiation field by
      computerized tomography (CT) and magnetic resonance imaging (MRI) and
      appreciation of the expected latency period may help in providing the diagnosis
      of RIS. 

PMID- 24742096
TI  - Pattern formation and coarse-graining in two-dimensional colloids driven by
      multiaxial magnetic fields.
AB  - We study the pattern formation in a two-dimensional system of superparamagnetic
      colloids interacting via spatially coherent induced interactions driven by an
      external precessing magnetic field. On the pair level, upon changing the opening
      angle of the external field, the interactions smoothly vary from purely repulsive
      (opening angle equal to zero) to purely attractive (time-averaged pair
      interactions at an opening angle of 90 degrees ). In the experiments, we observed
      ordered hexagonal crystals at the repulsive end and coarsening frothlike
      structures for purely attractive interactions. In both of these limiting cases,
      the dense colloidal systems can be sufficiently accurately described by assuming
      pairwise additivity of the interaction potentials. However, for a range of
      intermediate angles, pronounced many-body depolarization effects compete with the
      direct induced interactions, resulting in inherently anisotropic effective
      interactions. Under such conditions, we observed the decay of hexagonal order
      with the concomitant formation of short chains and percolated networks of chains
      coexisting with free colloids. In order to describe and investigate these systems
      theoretically, we developed a coarse-grained model of a binary mixture of patchy
      and nonpatchy particles with the ratio of patchy and nonpatchy colloids as the
      order parameter. Combining genetic algorithms with Monte Carlo simulations, we
      optimized the model parameters and quantitatively reproduced the experimentally
      observed sequence of colloidal structures. The results offer new insight into the
      anisotropy induced by the many-body effects. At the same time, they allow for a
      very efficient description of the system by means of a pairwise-additive
      Hamiltonian, whereupon the original, one-component system features a two
      component mixture of isotropic and patchy colloids. 

PMID- 24742095
TI  - Natural products and synthetic biology.

PMID- 24742098
TI  - Mammographic density and serum 25-hydroxyvitamin D levels.
AB  - BACKGROUND: Vitamin D, which influences cellular proliferation and breast tissue
      characteristics, has been inversely correlated with breast cancer risk. Dietary
      vitamin D intake has been associated with lower mammographic density (MD), a
      strong intermediate marker of breast cancer risk. FINDINGS: We examined the
      relationship between MD and serum 25-hydroxyvitamin D [25(OH)D], an integrated
      measure of vitamin D status from dietary sources and sunlight exposure, in a
      multi-ethnic cohort of women undergoing screening mammography. We recruited women
      age 40-60 years without a history of breast cancer at the time of their routine
      screening mammogram, and conducted in-person interviews and collected blood
      specimens. We enrolled 195 women from 2007-2008, 120 gave blood, and 114 were
      evaluable, including 25% white, 41% African American, 18% African Caribbean, and
      16% Hispanic. We digitized mammograms and calculated percent density, dense area,
      and non-dense area on cranial-caudal images. We measured serum 25(OH)D in
      batched, archived specimens. Median serum 25(OH)D was 22 ng/ml (range, 8-66
      ng/ml). In univariable analysis, higher serum 25(OH)D was associated with white
      race, higher educational level, ever breast feeding, and blood draw during the
      summer. After adjusting for body mass index and other confounders, we found no
      association between serum 25(OH)D and different measures of MD. However, when
      stratified by season, 25(OH)D was inversely associated with dense area during
      July-December (p = 0.034). CONCLUSIONS: Overall, our findings suggest that
      circulating vitamin D, a potentially modifiable breast cancer risk factor, is not
      associated with MD; the seasonal effects we observed need to be replicated in
      larger cohorts.

PMID- 24742099
TI  - Absence of association of interleukin-18 gene polymorphisms with primary immune
      thrombocytopenia in a Chinese Han population.
AB  - Interleukin-18 (IL-18) is an inflammatory cytokine that plays an important role
      in autoimmune disease by inducing interferon-gamma secretion. Considering the
      abnormal serum concentration of IL-18 in primary immune thrombocytopenia (ITP)
      patients and the regulated effect of IL-18 gene polymorphisms on its production,
      the aim of this study was to investigate a possible association between the IL-18
      promoter polymorphisms (-137 G/C and -607 C/A sites) and genetic susceptibility
      to ITP in a Chinese Han population. A total of 181 ITP patients and 163 healthy
      controls were included in this study; IL-18 gene promoter polymorphisms were
      analyzed by a polymerase chain reaction with sequence-specific primers. No
      significant differences in genotype (-607: chi(2)=0.307, p=0.858; -137:
      chi(2)=0.378, p=0.828) and allele frequencies (-607: chi(2)=0.004, p=0.949; -137:
      chi(2)=0.307, p=0.858) were found between total ITP patients and normal controls.
      We further analyzed the association of IL-18 polymorphisms with clinical
      parameters of ITP patients, including first onset age and clinical therapy
      response to glucocorticoids, and no difference was revealed. In conclusion, IL-18
      promoter polymorphisms may not be associated with genetic susceptibility to ITP
      in a Chinese Han population. 

PMID- 24742101
TI  - Crack formation on resected root surfaces subjected to conventional, ultrasonic,
      and laser root-end cavity preparation.
AB  - OBJECTIVE: The aim of this study was to evaluate cracks on root ends following
      resection and cavity preparation with a laser and two established techniques.
      BACKGROUND DATA: If root canal treatment of a tooth fails, an apicoectomy
      operation may be indicated. Three millimeters of the root tip is resected and a
      cavity of similar depth with parallel walls is cut to receive a root-end filling.
      MATERIALS AND METHODS: Sixty extracted human maxillary anterior teeth were used.
      Their root canals were prepared with rotary instruments, and they were filled
      with gutta-percha. Twenty teeth were resected with tungsten carbide fissure burs,
      and their root-end cavities cut with tungsten carbide round burs at a slow speed
      (Group 1). The other 40 teeth were resected with an Er:YAG laser, and root-end
      cavities were made with the same laser (Group 2), or with an ultrasonically
      powered zirconium nitride coated retrotip (Group 3). The number and types of
      cracks on the resected surfaces were assessed using a stereomicroscope before and
      after cavity preparation. RESULTS: Cracking was not significantly different
      between the more conventional group and the laser groups after resections
      (p>0.05) or following cavity preparation (p>0.05). CONCLUSIONS: In this in vitro
      study, the laser resection and root-end preparation technique did not influence
      the number or type of cracks formed on the root surfaces.

PMID- 24742100
TI  - Deciphering gamma-decalactone biosynthesis in strawberry fruit using a
      combination of genetic mapping, RNA-Seq and eQTL analyses.
AB  - BACKGROUND: Understanding the basis for volatile organic compound (VOC)
      biosynthesis and regulation is of great importance for the genetic improvement of
      fruit flavor. Lactones constitute an essential group of fatty acid-derived VOCs
      conferring peach-like aroma to a number of fruits including peach, plum,
      pineapple and strawberry. Early studies on lactone biosynthesis suggest that
      several enzymatic pathways could be responsible for the diversity of lactones,
      but detailed information on them remained elusive. In this study, we have
      integrated genetic mapping and genome-wide transcriptome analysis to investigate
      the molecular basis of natural variation in gamma-decalactone content in
      strawberry fruit. RESULTS: As a result, the fatty acid desaturase FaFAD1 was
      identified as the gene underlying the locus at LGIII-2 that controls gamma
      decalactone production in ripening fruit. The FaFAD1 gene is specifically
      expressed in ripe fruits and its expression fully correlates with the presence of
      gamma-decalactone in all 95 individuals of the mapping population. In addition,
      we show that the level of expression of FaFAH1, with similarity to cytochrome
      p450 hydroxylases, significantly correlates with the content of gamma-decalactone
      in the mapping population. The analysis of expression quantitative trait loci
      (eQTL) suggests that the product of this gene also has a regulatory role in the
      biosynthetic pathway of lactones. CONCLUSIONS: Altogether, this study provides
      mechanistic information of how the production of gamma-decalactone is naturally
      controlled in strawberry, and proposes enzymatic activities necessary for the
      formation of this VOC in plants.

PMID- 24742102
TI  - Revealing controllable nanowire transformation through cationic exchange for RRAM
      application.
AB  - One dimensional metal oxide nanostructures have attracted much attention owing to
      their fascinating functional properties. Among them, piezoelectricity and
      photocatalysts along with their related materials have stirred significant
      interests and widespread studies in recent years. In this work, we successfully
      transformed piezoelectric ZnO into photocatalytic TiO2 and formed TiO2/ZnO axial
      heterostructure nanowires with flat interfaces by solid to solid cationic
      exchange reactions in high vacuum (approximately 10(-8) Torr) transmission
      electron microscope (TEM). Kinetic behavior of the single crystalline TiO2 was
      systematically analyzed. The nanoscale growth rate of TiO2 has been measured
      using in situ TEM videos. On the basis of the rate, we can control the dimensions
      of the axial-nanoheterostructure. In addition, the unique Pt/ ZnO / TiO2/ ZnO /Pt
      heterostructures with complementary resistive switching (CRS) characteristics
      were designed to solve the important issue of sneak-peak current. The resistive
      switching behavior was attributed to the migration of oxygen and TiO2 layer
      served as reservoir, which was confirmed by energy dispersive spectrometry (EDS)
      analysis. This study not only supplied a distinct method to explore the
      transformation mechanisms but also exhibited the potential application of
      ZnO/TiO2 heterostructure in nanoscale crossbar array resistive random-access
      memory (RRAM). 

PMID- 24742103
TI  - Corrigendum.

PMID- 24742104
TI  - Apoptosis induction in colon cancer cell lines and alteration of aberrant crypt
      foci in rat colon by purple rice (Oryza sativa L. var. glutinosa) extracts.
AB  - Crude ethanol extracts (CEE) of purple rice was fractionated to obtain hexane
      soluble (HSF) and ethyl acetate soluble fractions (EASF). Total antioxidant
      capacity was higher in CEE than the HSF and EASF. However, HSF exhibited strong
      antiproliferation and apoptosis induction against colon cancer cell lines, both
      p53 wild-type (RKO) and mutant (SW620) strains. Then, the CEE was used to
      determine the effects on the progression of aberrant crypt foci (ACF), a
      preneoplastic lesion seen in colon carcinogenesis in rats. Male Wistar rats were
      subcutaneously injected of 40 mg/kg body weight dimethylhydrazin (DMH) once
      weekly for 2 wk. After 2 wk, rats were orally administered ethanol extract at 100
      and 1000 mg/kg body weight, for 4 wk. Rats fed with only the high dose of CEE had
      significantly decreased numbers of ACF per rat (45.56%) and crypt multiplicity
      (AC/focus) (16.67%) compared to rats that received DMH alone. The result also
      demonstrated that CEE induced apoptosis in colonic epithelium cells of rat
      received colon carcinogen as detected the increasing of caspase-3 activity. This
      finding could be concluded that purple rice extracts inhibited aberrant colonic
      epithelial cell progression via apoptosis induction. 

PMID- 24742105
TI  - Successful control of a neonatal outbreak caused mainly by ST20 multidrug
      resistant SHV-5-producing Klebsiella pneumoniae, Greece.
AB  - BACKGROUND: Extended spectrum beta-lactamase-producing Klebsiella pneumoniae
      (ESBL-Kp) infection can cause significant morbidity and mortality in neonates. We
      investigated a nosocomial ESBL-Kp outbreak in a neonatal intensive care unit
      (NICU) of the University Hospital of Larissa (UHL), Central Greece. METHODS: A
      total of sixty-four ESBL-Kp were studied; twenty six isolates were recovered from
      the NICU and were compared with thirty-eight randomly selected isolates from
      different wards of the hospital during the period March- December 2012. All
      isolates were characterized by antimicrobial susceptibility testing, ESBL
      production by double-disk synergy test, molecular typing using BOX-PCR, whereas
      selected isolates were further characterized by beta lactamase and virulence gene
      content, multilocus sequence typing and phylogenetic analysis. All neonates
      affected by ESBL-Kp were put under strict contact isolation, along with
      appropriate infection control measures. RESULTS: The outbreak strain of ST20
      multidrug-resistant SHV-5-producing K. pneumoniae was identified in all infected
      (n = 13) and three colonized neonates. A novel ST (ST1114) was also identified
      among SHV-5 producers (n = 10) recovered from nine colonized infants, but it was
      not related with ST20. Both STs were identified only in the NICU and not in other
      wards of the hospital. No ESBL-Kp were isolated from the hands of the nursing
      staff and the environment. Although we were not able to identify the source of
      the outbreak, no ESBL-Kp were isolated in the NICU after this period and we
      assumed that the outbreak was successfully controlled. All neonates received
      parenteral nutrition and most of them were delivered by caesarean section and
      showed low gestational age (<32 weeks) and low birth weights (<1500 g).
      CONCLUSION: According to our knowledge, this is the first description of an
      outbreak of multidrug-resistant SHV-5 producing K. pneumoniae assigned to ST20.

PMID- 24742106
TI  - Total synthesis of panaginsene with structural revision.
AB  - A facile total synthesis of the reported structure for panaginsene through a
      trimethylenemethane (TMM) diyl mediated tandem cycloaddition reaction revealed
      that the spectroscopic data of the synthesized structure did not match with the
      data of the natural product. The total synthesis of the stereoisomer of the
      reported structure confirmed that the correct structure of panaginsene was the 11
      epi stereoisomer of the originally proposed structure of panaginsene. 

PMID- 24742107
TI  - Cyclin E involved in early stage carcinogenesis of esophageal adenocarcinoma by
      SNP DNA microarray and immunohistochemical studies.
AB  - BACKGROUND: Cyclin E is a cell cycle regulator which is critical for driving G1/S
      transition. Abnormal levels of cyclin E have been found in many cancers. However,
      the level changes of cyclin E in esophageal adenocarcinoma and its precancerous
      lesion have not been well studied. Here, we focus on the gene amplification and
      expression of cyclin E in these lesions, and aim to ascertain the relationship
      with clinicopathological characteristics. METHODS: Genomic DNA was analyzed from
      116 esophageal adenocarcinoma and 26 precancerous lesion patients using
      Affymetrix SNP 6.0 arrays. The protein overexpression of cyclin E was also
      detected using immunohistochemistry from tissue microarrays containing esophageal
      adenocarcinoma and precancerous lesions. Patient survival and other clinical data
      were collected and analyzed. The intensity and percentage of the cyclin E
      expressing cells in tissue microarrays were scored by two pathologists. Fisher
      exact tests and Kaplan-Meier methods were used to analyze data. RESULTS: By
      genomic analysis, cyclin E was amplified in 19.0% of the EAC samples. By
      immunohistochemistry, high expression of cyclin E was observed in 2.3% of
      squamous mucosa tissues, 3.7% in columnar cell metaplasia, 5.8% in Barrett's
      esophagus, 19.0% in low grade dysplasia, 35.7% in high grade dysplasia, and 16.7%
      in esophageal adenocarcinoma. The differences in cyclin E high expression between
      neoplastic groups and non-dysplasia groups are statistically significant (p <
      0.05). The prognosis for patients with high cyclin E expression appeared slightly
      better than for those with low cyclin E expression although this was not
      statistically significant (p = 0.13). CONCLUSIONS: The expression of cyclin E
      significantly increases from non-dysplasia esophageal lesion to low and high
      grade dysplasia, suggesting that cyclin E plays an important role in the early
      stage of carcinogenesis. Importantly, cyclin E is also amplified and highly
      expressed in a subset of esophageal adenocarcinoma patients, but this increase is
      not associated with worse prognosis.

PMID- 24742109
TI  - Editorial for the special issue on uncertainty in the brain.

PMID- 24742108
TI  - Rickettsia bellii, Rickettsia amblyommii, and Laguna Negra hantavirus in an
      Indian reserve in the Brazilian Amazon.
AB  - BACKGROUND: The purpose of this study was to identify the presence of rickettsia
      and hantavirus in wild rodents and arthropods in response to an outbreak of acute
      unidentified febrile illness among Indians in the Halataikwa Indian Reserve,
      northwest of the Mato Grosso state, in the Brazilian Amazon. Where previously
      surveillance data showed serologic evidence of rickettsia and hantavirus human
      infection. METHODS: The arthropods were collected from the healthy Indian
      population and by flagging vegetation in grassland or woodland along the
      peridomestic environment of the Indian reserve. Wild rodents were live-trapped in
      an area bordering the reserve limits, due the impossibility of capturing wild
      animals in the Indian reserve. The wild rodents were identified based on external
      and cranial morphology and karyotype. DNA was extracted from spleen or liver
      samples of rodents and from invertebrate (tick and louse) pools, and the
      molecular characterization of the rickettsia was through PCR and DNA sequencing
      of fragments of two rickettsial genes (gltA and ompA). In relation to hantavirus,
      rodent serum samples were serologically screened by IgG ELISA using the
      Araraquara-N antigen and total RNA was extracted from lung samples of IgG
      positive rodents. The amplification of the complete S segment was performed.
      RESULTS: A total of 153 wild rodents, 121 louse, and 36 tick specimens were
      collected in 2010. Laguna Negra hantavirus was identified in Calomys callidus
      rodents and Rickettsia bellii, Rickettsia amblyommii were identified in Amblyomma
      cajennense ticks. CONCLUSIONS: Zoonotic diseases such as HCPS and spotted fever
      rickettsiosis are a public health threat and should be considered in outbreaks
      and acute febrile illnesses among Indian populations. The presence of the genome
      of rickettsias and hantavirus in animals in this Indian reserve reinforces the
      need to include these infectious agents in outbreak investigations of febrile
      cases in Indian populations.

PMID- 24742110
TI  - Mammotome-assisted endoscopic breast-conserving surgery: a novel technique for
      early-stage breast cancer.
AB  - BACKGROUND: Because of its minimally invasive and highly accurate nature, the use
      of Mammotome, a vacuum-assisted breast biopsy device has proven beneficial to the
      treatment of benign breast lesions. Taking advantage of endoscopic and Mammotome
      techniques together, we utilized the Mammotome device for therapeutic excision of
      malignant lesions in breast-conserving surgery (BCS). METHODS: Between December
      2009 and January 2010, two patients with early breast cancer received Mammotome
      assisted endoscopic BCSs. Under ultrasound monitoring, the Mammotome system
      dissected the surrounding tissue and freed the tumor en bloc leaving negative
      margins; endoscopic axillary lymph node dissection then followed. RESULTS: The
      operation time was less than 180 minutes and the mean blood loss was 60 ml. The
      post-operative pathology report confirmed two patients to have invasive ductal
      carcinoma, one without axillary lymph nodes metastasis (0/11) and the other with
      one lymph node metastasis (1/21). No adverse events were noted. During a mean
      follow-up of 26.5 months, no evidence of recurrence or metastasis was found. The
      patients were satisfied with the cosmetic results. CONCLUSIONS: Mammotome
      assisted endoscopic surgery appears to be a valuable option for early breast
      cancer. The long-term therapeutic effect remains to be confirmed.

PMID- 24742111
TI  - Vitamin K1 attenuates bile duct ligation-induced liver fibrosis in rats.
AB  - Vitamin K1 is used as a liver protection drug for cholestasis-induced liver
      fibrosis in China, but the mechanism of vitamin K1's action in liver fibrosis is
      unclear. In this study, a model of liver fibrosis was achieved via bile duct
      ligation in rats. The rats were then injected with vitamin K1, and the levels of
      serum aspartate aminotransferase, alanine transaminase, total bilirubin and the
      fibrotic grade score, collagen content, the expressions of alpha-smooth muscle
      actin (SMA) and cytokeratin 19 (CK19) were measured on day 28 after ligation. The
      levels of the biochemical parameters, fibrotic score and collagen content were
      significantly reduced by treatment with vitamin K1 in bile duct-ligated rats. In
      addition, alpha-SMA and CK19 expression was significantly reduced by vitamin K1
      treatment in bile duct-ligated rats. These results suggested that vitamin K1 may
      attenuate liver fibrosis by inhibiting hepatic stellate cell activation in bile
      duct-ligated rats.

PMID- 24742112
TI  - Prader-Willi syndrome, excessive daytime sleepiness, and narcoleptic symptoms: a
      case report.
AB  - INTRODUCTION: Sleep abnormalities, including narcolepsy and cataplexy, are a
      common feature of Prader-Willi syndrome. Long-term treatment with the central
      nervous system stimulant modafinil has not been reported. In this case report we
      present a longitudinal perspective of sleep abnormalities in a nine-year-old
      Caucasian girl with Prader-Willi syndrome from age two to age nine, and detail
      the response to treatment with the central nervous system stimulant modafinil.
      CASE PRESENTATION: Our patient presented at two years of age with hypersomnia and
      narcoleptic episodes with cataplectic features. Initial polysomnograph testing
      revealed adequate sleep efficiency, but increased sleep fragmentation especially
      during rapid eye movement sleep. The narcoleptic episodes continued and a repeat
      polysomnograph at age five years confirmed features consistent with narcolepsy.
      Further sleep studies at six years, including a multiple sleep latency test,
      demonstrated signs of excessive daytime sleepiness. Treatment with modafinil was
      initiated at age seven years six months due to persistent hypersomnia and
      narcoleptic symptoms. Two polysomnograph studies were performed following
      treatment with modafinil, at age eight years six months and nine years three
      months. These studies showed excellent sleep efficiency and improvement of rapid
      eye movement sleep parameters, supporting the beneficial effects of long-term
      modafinil therapy. CONCLUSIONS: Long-term modafinil therapy may ameliorate the
      sleep disturbances of Prader-Willi syndrome and should be the focus of future
      clinical trials.

PMID- 24742113
TI  - "Nudge" in the clinical consultation--an acceptable form of medical paternalism?
AB  - BACKGROUND: Libertarian paternalism is a concept derived from cognitive
      psychology and behavioural science. It is behind policies that frame information
      in such a way as to encourage individuals to make choices which are in their best
      interests, while maintaining their freedom of choice. Clinicians may view their
      clinical consultations as far removed from the realms of cognitive psychology but
      on closer examination there are a number of striking similarities. DISCUSSION:
      Evidence has shown that decision making is prone to bias and not necessarily
      rational or logical, particularly during ill health. Clinicians will usually have
      an opinion about what course of action represents the patient's best interests
      and thus may "frame" information in a way which "nudges" patients into making
      choices which are considered likely to maximise their welfare. This may be viewed
      as interfering with patient autonomy and constitute medical paternalism and
      appear in direct opposition to the tenets of modern practice. However, we argue
      that clinicians have a responsibility to try and correct "reasoning failure" in
      patients. Some compromise between patient autonomy and medical paternalism is
      justified on these grounds and transparency of how these techniques may be used
      should be promoted. SUMMARY: Overall the extremes of autonomy and paternalism are
      not compatible in a responsive, responsible and moral health care environment,
      and thus some compromise of these values is unavoidable. Nudge techniques are
      widely used in policy making and we demonstrate how they can be applied in shared
      medical decision making. Whether or not this is ethically sound is a matter of
      continued debate but health care professionals cannot avoid the fact they are
      likely to be using nudge within clinical consultations. Acknowledgment of this
      will lead to greater self-awareness, reflection and provide further avenues for
      debate on the art and science of clinical communication.

PMID- 24742114
TI  - Access to care--an unmet need in headache management?
AB  - Access to care for headache sufferers is not always simple. A survey conducted in
      a large number of members of lay associations point to the existence of multiple
      barriers to care for headache in several European countries. Patients usually
      discover the existence of specialized structures with a delay of several years
      after the onset of their headache. Furthermore, a relevant portion of them are
      not satisfied with the management of their disease, partly because of the poor
      efficacy of treatments and partly because of the difficulty to get in touch with
      the specialist. Headache disorders, and primary headaches in particular,
      represent an important issue in public health, because they are common, disabling
      and treatable. A joint effort is required from the relevant stakeholders
      (scientists, lay organizations, decision-makers, healthcare policymakers, and
      others) to improve the access to care for headache sufferers. 

PMID- 24742115
TI  - Yeast synthetic biology platform generates novel chemical structures as scaffolds
      for drug discovery.
AB  - Synthetic biology has been heralded as a new bioengineering platform for the
      production of bulk and specialty chemicals, drugs, and fuels. Here, we report for
      the first time a series of 74 novel compounds produced using a combinatorial
      genetics approach in baker's yeast. Based on the concept of "coevolution" with
      target proteins in an intracellular primary survival assay, the identified,
      mostly scaffold-sized (200-350 MW) compounds, which displayed excellent
      biological activity, can be considered as prevalidated hits. Of the molecules
      found, >75% have not been described previously; 20% of the compounds exhibit
      novel scaffolds. Their structural and physicochemical properties comply with
      established rules of drug- and fragment-likeness and exhibit increased structural
      complexities compared to synthetically produced fragments. In summary, the
      synthetic biology approach described here represents a completely new,
      complementary strategy for hit and early lead identification that can be easily
      integrated into the existing drug discovery process. 

PMID- 24742116
TI  - Symptom reduction due to psychosocial interventions is not accompanied by a
      reduction in sick leave: results from a randomized controlled trial in primary
      care.
AB  - OBJECTIVE: To investigate whether interventions that have positive effects on
      psychological symptoms and quality of life compared with usual care would also
      reduce days on sick leave. DESIGN: A randomized controlled trial. SETTING: A
      large primary health care centre in Stockholm, Sweden. Intervention. Patients
      with common mental disorders were recruited by their GPs and randomized into one
      of two group interventions that took place in addition to usual care. These group
      interventions were: (a) group cognitive behavioural therapy (CBT), and (b) group
      multimodal intervention (MMI). Both types of intervention had previously shown
      significant effects on quality of life, and MMI had also shown significant
      effects on psychological symptoms. PATIENTS: Of the 245 randomized patients, 164
      were employed and had taken sick leave periods of at least two weeks in length
      during the study period of two years. They comprised the study group. MAIN
      OUTCOME MEASURES: The odds, compared with usual care, for being sick-listed at
      different times relative to the date of randomization. RESULTS: The mean number
      of days on sick leave increased steadily in the two years before randomization
      and decreased in the two years afterwards, showing the same pattern for all three
      groups .The CBT and MMI interventions did not show the expected lower odds for
      sick-listing compared with usual care during the two-year follow-up. CONCLUSION:
      Reduction in psychological symptoms and increased well-being did not seem to be
      enough to reduce sickness absence for patients with common mental problems in
      primary care. The possibility of adding workplace-oriented interventions is
      discussed.

PMID- 24742117
TI  - Preparation of ultrathin nanowires using superfluid helium droplets.
AB  - Direct preparation of long one-dimensional (1D) nanostructures with diameters <10
      nm inside superfluid helium droplets is reported. Unlike conventional chemical
      synthetic techniques, where stabilizers, templates, or external fields are often
      required to induce 1D growth, here, we exploit the use of quantized vortices to
      guide the formation of ultrathin nanowires. A variety of elements have been added
      to the droplets to demonstrate that this is a general phenomenon, including Ni,
      Cr, Au, and Si. Control of the length and diameter of the nanowires is also
      demonstrated. 

PMID- 24742118
TI  - Diagnosis of cervical cells based on fractal and Euclidian geometrical
      measurements: Intrinsic Geometric Cellular Organization.
AB  - BACKGROUND: Fractal geometry has been the basis for the development of a
      diagnosis of preneoplastic and neoplastic cells that clears up the
      undetermination of the atypical squamous cells of undetermined significance
      (ASCUS). METHODS: Pictures of 40 cervix cytology samples diagnosed with
      conventional parameters were taken. A blind study was developed in which the
      clinic diagnosis of 10 normal cells, 10 ASCUS, 10 L-SIL and 10 H-SIL was masked.
      Cellular nucleus and cytoplasm were evaluated in the generalized Box-Counting
      space, calculating the fractal dimension and number of spaces occupied by the
      frontier of each object. Further, number of pixels occupied by surface of each
      object was calculated. Later, the mathematical features of the measures were
      studied to establish differences or equalities useful for diagnostic application.
      Finally, the sensibility, specificity, negative likelihood ratio and diagnostic
      concordance with Kappa coefficient were calculated. RESULTS: Simultaneous
      measures of the nuclear surface and the subtraction between the boundaries of
      cytoplasm and nucleus, lead to differentiate normality, L-SIL and H-SIL.
      Normality shows values less than or equal to 735 in nucleus surface and values
      greater or equal to 161 in cytoplasm-nucleus subtraction. L-SIL cells exhibit a
      nucleus surface with values greater than or equal to 972 and a subtraction
      between nucleus-cytoplasm higher to 130. L-SIL cells show cytoplasm-nucleus
      values less than 120. The rank between 120-130 in cytoplasm-nucleus subtraction
      corresponds to evolution between L-SIL and H-SIL. Sensibility and specificity
      values were 100%, the negative likelihood ratio was zero and Kappa coefficient
      was equal to 1. CONCLUSIONS: A new diagnostic methodology of clinic applicability
      was developed based on fractal and euclidean geometry, which is useful for
      evaluation of cervix cytology.

PMID- 24742119
TI  - The non-metabolizable glucose analog D-glucal inhibits aflatoxin biosynthesis and
      promotes kojic acid production in Aspergillus flavus.
AB  - BACKGROUND: Aflatoxins (AFs) are potent carcinogenic compounds produced by
      several Aspergillus species, which pose serious threats to human health. As sugar
      is a preferred carbohydrate source for AF production, we examined the possibility
      of using sugar analogs to inhibit AF biosynthesis. RESULTS: We showed that
      although D-glucal cannot be utilized by A. flavus as the sole carbohydrate
      source, it inhibited AF biosynthesis and promoted kojic acid production without
      affecting mycelial growth when applied to a glucose-containing medium. The
      inhibition occurred before the production of the first stable intermediate,
      norsolorinic acid, suggesting a complete inhibition of the AF biosynthetic
      pathway. Further studies showed that exogenous D-glucal in culture led to reduced
      accumulation of tricarboxylic acid (TCA) cycle intermediates and reduced glucose
      consumption, indicating that glycolysis is inhibited. Expression analyses
      revealed that D-glucal suppressed the expression of AF biosynthetic genes but
      promoted the expression of kojic acid biosynthetic genes. CONCLUSIONS: D-glucal
      as a non-metabolizable glucose analog inhibits the AF biosynthesis pathway by
      suppressing the expression of AF biosynthetic genes. The inhibition may occur
      either directly through interfering with glycolysis, or indirectly through
      reduced oxidative stresses from kojic acid biosynthesis.

PMID- 24742121
TI  - Glucocorticoid therapy for gastrointestinal diseases.
AB  - INTRODUCTION: Glucocorticoids are widely used as anti-inflammatory and
      immunosuppressive agents in many immune-mediated gastrointestinal diseases.
      However, a number of undesirable side effects may occur and dictate continuous
      surveillance and monitoring to prevent complications. AREAS COVERED: This review
      of the English language literature identified on PubMed focuses on key aspects of
      glucocorticoid therapy in patients with gastrointestinal diseases, highlighting
      specific aspects of recognition and management of its secondary effects. EXPERT
      OPINION: Long-term cohort studies as well as placebo- and sham-controlled trials
      have evaluated the clinical efficacy, safety and tolerability of glucocorticoid
      therapy in many gastrointestinal diseases. Other immunosuppressive and biological
      therapies have made glucocorticoid therapy part of a broader arsenal of
      therapies. Newer compounds that carry less systemic toxicity and improved
      tolerability are increasingly used. For several gastrointestinal diseases, the
      role of the mucosal immunity is currently being explored and microscopic
      inflammation of the intestinal mucosa may have an important pathogenetic role.
      Glucocorticoid therapy, particularly with newer, safer compounds, may play an
      important new role in patients with altered motility and visceral
      hypersensitivity. The interplay of the gut microbiota and the host that
      contributes to the development of gut-associated lymphoid tissues and gut
      specific immune responses will also undoubtedly be explored.

PMID- 24742120
TI  - Immunosenescence in the nursing home elderly.
AB  - BACKGROUND: To describe T-cell and natural killer (NK) cell phenotypes within
      nursing home elderly. METHODS: Nursing home elderly were recruited from four
      nursing homes in Hamilton, Ontario between September 2010 and December 2011.
      Healthy adults were recruited from McMaster University between September 2011 and
      December 2011. Nursing home elderly >=65 years were eligible; those on
      immunosuppressive medications were excluded. Healthy adults >=18-64 years were
      eligible. CD8+ and CD4+ T-cells% and their subsets, T-regs% and NK cell subset%
      were compared between the nursing home elderly and healthy adults. RESULTS: 262
      nursing home elderly were enrolled; median age 87 years and 81% were female. 16
      healthy adults were enrolled; median age 31 and 50% were female. There was no
      significant difference between CD8+ T-cell% in nursing home and healthy adults
      (median 17.1 versus 18.0, p = 0.56), however there were fewer naive CD8 + T-cell%
      (median 0.9 versus 5.2, p < 0.001), more terminally differentiated CD8 + T-cell%
      (median 7.3 versus 4.1, p = 0.004) and more senescent T-cell% (median 5.3 versus
      3.1, p = 0.04) in the nursing home elderly. There were more CD4+ T-cell% in the
      nursing home elderly compared to healthy adults (median 45.5 versus 37.1, p =
      0.001). Nursing home elderly had a higher CD4+/CD8+ ratio than healthy adults
      (2.6 versus 1.9, p = 0.048), higher T-reg% (median 1.8 versus 0.8, p < 0.001) and
      increased mature NK cell% (median 12.1 versus 5.4, p = 0.001) compared to healthy
      adults. CONCLUSION: Differences in naive CD8+ T-cells, terminally differentiated
      and senescent CD8+ T-cells, T-regs and NK cell subsets were similar to studies
      involving community dwelling elderly. In contrast, the CD4+/CD8+ ratio was higher
      in nursing home elderly.

PMID- 24742123
TI  - Association between sex steroids, ovarian reserve, and vitamin D levels in
      healthy nonobese women.
AB  - CONTEXT: Vitamin D maintains calcium and phosphorous homeostasis and promotes
      bone mineralization; however, its nonskeletal functions are increasingly being
      recognized. Recent evidence supports a role for vitamin D in reproductive
      potential, but few studies have investigated the potential effects of vitamin D
      on reproductive hormone biosynthesis and ovarian reserve. OBJECTIVE: The aim of
      this study was to determine the relationships between the serum level of vitamin
      D, reproductive hormone levels, and ovarian reserve in healthy nonobese women.
      DESIGN: This was a cross-sectional study. SETTING: The study was performed at the
      Fertility Center at CHA Medical Center. PARTICIPANTS: Seventy-three healthy women
      volunteers participated in this study. The participants were nonobese parous
      women with regular menstrual cycles and no history of infertility. MAIN OUTCOME
      MEASURES: We determined serum levels of vitamin D, steroid hormones, SHBG,
      ovarian reserve markers, homeostatic model assessment of insulin resistance
      index, and lipid profiles. RESULTS: In linear regression analysis adjusting for
      age, body mass index, homeostatic model assessment of insulin resistance, and
      lipid profile, serum vitamin D level positively correlated with total T (P <
      .001) and free androgen index (P < .001) but did not correlate with
      dehydroepiandrosterone sulfate or other steroid hormones. The spline regression
      suggested relationship between 25-hydroxyvitamin D and total T was most
      pronounced at a 25-hydroxyvitamin D concentration greater than 13 ng/mL (beta
      coefficient 2.374, 95% confidence interval 1.435-3.313). The serum vitamin D
      level was not associated with the levels of ovarian reserve markers. CONCLUSION:
      Our study revealed a positive correlation between serum vitamin D level and T
      level in healthy nonobese women, suggesting that vitamin D may increase fertility
      through the modulation of androgen activity. The possible causality of the
      relationship between vitamin D and T deserves further investigation.

PMID- 24742124
TI  - Body composition is improved during 12 months' treatment with metformin alone or
      combined with oral contraceptives compared with treatment with oral
      contraceptives in polycystic ovary syndrome.
AB  - CONTEXT: Central obesity in polycystic ovary syndrome (PCOS) is associated with
      increased inflammatory markers and increased risk for type 2 diabetes. OBJECTIVE:
      The objective of the study was to evaluate whether treatment with metformin (M)
      or M combined with oral contraceptive pills (OCPs) resulted in a more
      advantageous body composition than treatment with OCP alone. SETTING: The study
      was conducted at an outpatient clinic. PATIENTS AND INTERVENTIONS: This was a
      randomized, controlled clinical trial. Ninety patients with PCOS were randomized
      to 12 months' treatment with M (2 g/d), M + OCP (150 mg desogestrel+30 MUg
      ethinylestradiol), or OCP. Whole-body dual-energy x-ray absorptiometry scans and
      clinical and hormonal evaluations were performed before and after the
      intervention period. A total of 65 of 90 patients completed the study. MAIN
      OUTCOME MEASURES: Changes in weight at 6 and 12 months and changes in regional
      fat mass estimates at 12 months were measured. RESULTS: Dropout rates between
      intervention groups were not significantly different. Treatment with M and M+OCP
      were superior to OCP regarding weight and regional fat mass. The median
      (quartiles) weight changes during 12 months of M, M+OCP, and OCP treatment were 
      3.0 (-10.3; 0.6), -1.9 (-4.9; 0.1), and 1.2 (-0.8; 3.0) kg, respectively, P <
      .05. Upper to lower fat mass ratio was unchanged. Changes in body composition
      were predicted by the type of medical intervention (M, M+OCP, or OCP) and not by
      body mass index at study inclusion. OCP and M+OCP were superior to M regarding
      reduction in free T levels. CONCLUSIONS: M treatment alone or in combination with
      OCP was associated with weight loss and improved body composition compared with
      OCP, whereas free T levels decreased during M+OCP or OCP. Combined treatment with
      M+OCP should be considered as an alternative to treatment with OCP alone to avoid
      weight gain in PCOS.

PMID- 24742125
TI  - Interleukin-10 attenuation of collagen-induced arthritis is associated with
      suppression of interleukin-17 and retinoid-related orphan receptor gammat
      production in macrophages and repression of classically activated macrophages.
AB  - INTRODUCTION: Our objective in the present study was to determine the signaling
      pathway of interleukin 10 (IL-10) for modulating IL-17 expression in macrophages
      and the importance of this mediation in collagen-induced arthritis (CIA).
      METHODS: IL-10-knockout (IL-10-/-) mice and wild-type (WT) mice were immunized
      with chicken type II collagen (CII) to induce arthritis. The expression levels of
      IL-17 and retinoid-related orphan receptor gammat (RORgammat) in macrophages and
      joint tissues of IL-10-/- and WT mice were analyzed by enzyme-linked
      immunosorbent assay, quantitative RT-PCR (qRT-PCR) and Western blotting. The
      F4/80 macrophages and positive IL-17-producing macrophages in synovial tissues of
      the mice were determined by immunohistochemistry. The populations of classically
      activated macrophage (M1) and alternatively activated macrophage (M2) phenotypes
      were analyzed by flow cytometry. The expression of genes associated with M1 and
      M2 markers was analyzed by qRT-PCR. RESULTS: Compared to WT mice, IL-10-/- mice
      had exacerbated CIA development, which was associated with increased production
      of T helper 17 cell (Th17)/Th1 proinflammatory cytokines and CII-specific
      immunoglobulin G2a antibody after CII immunization. Macrophages in IL-10-/- mice
      had increased amounts of IL-17 and RORgammat compared with the amounts in WT mice
      with CIA. Immunofluorescence microscopy showed that the number of IL-17-producing
      macrophages in synovial tissues was significantly higher in IL-10-/- mice than in
      WT mice. IL-10 deficiency might promote macrophage polarization toward the
      proinflammatory M1 phenotype, which contributes to the rheumatoid arthritis
      inflammation response. CONCLUSION: IL-10 inhibits IL-17 and RORgammat expression
      in macrophages and suppresses macrophages toward the proinflammatory M1
      phenotype, which is important for the role of IL-10 in mediating the pathogenesis
      of CIA.

PMID- 24742126
TI  - On your feet: protocol for a randomized controlled trial to compare the effects
      of pole walking and regular walking on physical and psychosocial health in older
      adults.
AB  - BACKGROUND: Physical activity is associated with better physical and mental
      health in older adults. Pole walking is a form of walking which may have
      additional health benefits in older adults, because of the addition of hand held
      poles, and consequent upper limb involvement. However, few studies have examined
      the potential additional effects of pole walking on physical and psychosocial
      health in older adults compared with walking. The aim of this study is to compare
      the effect of a pole walking program with the effects of a walking program, on
      physical and psychosocial wellbeing, in older adults in assisted living
      facilities. METHODS/DESIGN: Sixty men and women from assisted living communities
      over 65 years will be recruited from senior retirement facilities and randomized
      into a group based, pole walking program, or walking program. The pole walking
      group will use the Exerstrider method of pole walking. Total duration of the
      programs is 12 weeks, with three sessions per week, building from 20 minute to 30
      minute sessions.The primary outcome is physical function, as measured by items
      from the Seniors Fitness Test and hand grip strength. Secondary outcomes include,
      physical activity levels, sedentary behaviour, joint pain, and quality of life.
      All outcomes will be assessed before and after the programs, using valid and
      reliable measures. DISCUSSION: The study will add to the evidence base for the
      effects of pole walking, compared with walking, on physical and psychosocial
      health and physical function, in healthy older adults. This will improve
      understanding about the feasibility of pole walking programs and its specific
      benefits in this population. TRIAL REGISTRATION: Australian New Zealand Clinical
      Trials Registry ACTRN12612001127897.

PMID- 24742128
TI  - Short total synthesis of (-)-kainic acid.
AB  - A short total synthesis of (-)-kainic acid has been developed involving a novel
      diastereofacial differentiating Cu-catalyzed Michael addition-cyclization
      reaction, which provided access to a chiral pyrroline in a highly stereoselective
      manner. The chiral pyrroline was converted to (-)-kainic acid via the
      stereoselective 1,4-reduction of the pyrroline double bond in three steps. 

PMID- 24742127
TI  - Prophylactic cannabinoid administration blocks the development of paclitaxel
      induced neuropathic nociception during analgesic treatment and following
      cessation of drug delivery.
AB  - BACKGROUND: Chemotherapeutic treatment results in chronic pain in an estimated 30
      40 percent of patients. Limited and often ineffective treatments make the need
      for new therapeutics an urgent one. We compared the effects of prophylactic
      cannabinoids as a preventative strategy for suppressing development of paclitaxel
      induced nociception. The mixed CB1/CB2 agonist WIN55,212-2 was compared with the
      cannabilactone CB2-selective agonist AM1710, administered subcutaneously (s.c.),
      via osmotic mini pumps before, during, and after paclitaxel treatment.
      Pharmacological specificity was assessed using CB1 (AM251) and CB2 (AM630)
      antagonists. The impact of chronic drug infusion on transcriptional regulation of
      mRNA markers of astrocytes (GFAP), microglia (CD11b) and cannabinoid receptors
      (CB1, CB2) was assessed in lumbar spinal cords of paclitaxel and vehicle-treated
      rats. RESULTS: Both WIN55,212-2 and AM1710 blocked the development of paclitaxel
      induced mechanical and cold allodynia; anti-allodynic efficacy persisted for
      approximately two to three weeks following cessation of drug delivery. WIN55,212
      2 (0.1 and 0.5 mg/kg/day s.c.) suppressed the development of both paclitaxel
      induced mechanical and cold allodynia. WIN55,212-2-mediated suppression of
      mechanical hypersensitivity was dominated by CB1 activation whereas suppression
      of cold allodynia was relatively insensitive to blockade by either CB1 (AM251; 3
      mg/kg/day s.c.) or CB2 (AM630; 3 mg/kg/day s.c.) antagonists. AM1710 (0.032 and
      3.2 mg/kg /day) suppressed development of mechanical allodynia whereas only the
      highest dose (3.2 mg/kg/day s.c.) suppressed cold allodynia. Anti-allodynic
      effects of AM1710 (3.2 mg/kg/day s.c.) were mediated by CB2. Anti-allodynic
      efficacy of AM1710 outlasted that produced by chronic WIN55,212-2 infusion. mRNA
      expression levels of the astrocytic marker GFAP was marginally increased by
      paclitaxel treatment whereas expression of the microglial marker CD11b was
      unchanged. Both WIN55,212-2 (0.5 mg/kg/day s.c.) and AM1710 (3.2 mg/kg/day s.c.)
      increased CB1 and CB2 mRNA expression in lumbar spinal cord of paclitaxel-treated
      rats in a manner blocked by AM630. CONCLUSIONS AND IMPLICATIONS: Cannabinoids
      block development of paclitaxel-induced neuropathy and protect against
      neuropathic allodynia following cessation of drug delivery. Chronic treatment
      with both mixed CB1/CB2 and CB2 selective cannabinoids increased mRNA expression
      of cannabinoid receptors (CB1, CB2) in a CB2-dependent fashion. Our results
      support the therapeutic potential of cannabinoids for suppressing chemotherapy
      induced neuropathy in humans.

PMID- 24742130
TI  - Acoustic radiation force impulse elastography and serum fibrosis markers in
      chronic hepatitis C.
AB  - OBJECTIVE: Liver biopsy (LB) remains the gold standard for the assessment of
      liver fibrosis, although it is invasive and can have complications. The present
      study compares several noninvasive methods of fibrosis assessment in chronic
      hepatitis C (CHC), including acoustic radiation force impulse (ARFI)
      elastography, aspartate aminotransferase:platelet ratio index (APRI), Forns, FIB
      4, and King scores versus percutaneous LB. MATERIAL AND METHODS: This prospective
      study enrolled 51 untreated CHC patients. Biological tests necessary for the
      calculation of the scores (according to the classic formulas) were performed
      within a week of LB. The time interval between LB and tissue stiffness, assessed
      according to the Metavir score, was <6 months. Cutoff values were determined
      using area under receiver-operating characteristic curves (AUROC). RESULTS: The
      best test for predicting significant fibrosis (F >=2 Metavir) was ARFI
      elastography with an AUROC of 0.90, followed by FIB-4 (AUROC = 0.86), King (AUROC
      = 0.85), Forns (AUROC = 0.84), and APRI (AUROC = 0.82). For a cutoff of 1.31 m/s,
      ARFI had 89.3% sensitivity (Se) and 87% specificity (Sp). The best test for
      predicting cirrhosis was ARFI elastography with an AUROC of 0.98, followed by FIB
      4 (AUROC = 0.94), King (AUROC = 0.90), APRI (AUROC = 0.82), and Forns (AUROC =
      0.81). For a cutoff of 1.95 m/s, ARFI had 100% Se and 95.2% Sp. CONCLUSION: ARFI
      elastography had very good accuracy for the assessment of liver fibrosis. It was
      more effective than APRI, Forns, King, and FIB-4 scores for the prediction of
      significant fibrosis and cirrhosis in CHC patients.

PMID- 24742131
TI  - Physician clinical management strategies and reasoning: a cross-sectional survey
      using clinical vignettes of eight common medical admissions.
AB  - BACKGROUND: Physicians often select clinical management strategies not strongly
      supported by evidence or guidelines. Our objective was to examine the likelihood
      of selecting, and rationale for pursuing, clinical management strategies with
      more or less guideline support among physicians using clinical vignettes of eight
      common medical admissions. METHODS: We conducted a cross-sectional survey using
      clinical vignettes of attending physicians and housestaff at one internal
      medicine program in New York City. Each clinical vignette included a brief
      clinical scenario and a varying number of clinical management strategies:
      diagnostic tests, consultations, and treatments, some of which had strong
      evidence or guideline support (Level 1 strategies) while others had limited
      evidence or guideline support (Level 3 strategies). Likelihood of selecting a
      given management strategy was assessed using Likert scales and multiple response
      options were used to indicate rationale(s) for selections. RESULTS: Our sample
      included 79 physicians; 68 (86%) were younger than 40 years of age, 34 (43%) were
      female. There were 31 attending physicians (39%) and 48 housestaff (61%) and 39
      (49%) had or planned to have primarily primary care internal medicine clinical
      responsibilities. Overall, physicians were more likely to select Level 1
      strategies "always" or "most of the time" when compared with Level 3 strategies
      (82% vs. 43%; p < 0.001), with wide variation across the eight medical
      admissions. There were no differences between attending and housestaff physician
      likelihood of selecting Level 3 strategies (47% vs. 45%, p = 0.36). Supportive
      evidence and local practice patterns were the two most common rationales behind
      selections; supportive evidence was cited as the most common rationale for
      selecting Level 1 when compared with Level 3 strategies (63% versus 30%; p <
      0.001), whereas ruling out other severe conditions was cited most often for Level
      3 strategies. CONCLUSIONS: For eight common medical admissions, physicians
      selected more than 80% of management strategies with strong evidence or guideline
      support, but also selected more than 40% of strategies for which there was
      limited evidence or guideline support. The promotion of evidence-based care,
      including the avoidance of care that is not strongly supported by evidence or
      guidelines, may require better evidence dissemination and educational outreach to
      physicians.

PMID- 24742132
TI  - Interferon beta-associated recurrence of painful trigeminal neuropathy attributed
      to a multiple sclerosis plaque.
AB  - We report the case of a 49-year-old woman with painful trigeminal neuropathy in
      the right maxillary division attributed to a multiple sclerosis plaque as the
      presenting symptom of multiple sclerosis. The patient was initially treated with
      intravenous corticosteroids and was pain free on pregabalin for six months. She
      was then started on an immunomodulatory treatment and coinciding with the up
      titration of interferon beta-1a, she experienced recurrence of painful trigeminal
      neuropathy as well as weekly migraine attacks. Worsening of primary headache
      disorders by interferon treatment has been previously reported. Our case suggests
      that treatment with interferon beta may also exacerbate symptomatic trigeminal
      neuralgia in multiple sclerosis. 

PMID- 24742133
TI  - Combined endoscopic surgery in the prone-split leg position for successful single
      session removal of an encrusted ureteral stent: a case report.
AB  - INTRODUCTION: Although encrusted stents may lead to some unwanted complications
      including urinary tract obstruction, urinary sepsis, and potential loss of kidney
      function, there is currently no consensus on the most efficient method for
      managing stents that are intentionally left in situ. This is the first report
      describing the management of an encrusted stent using combined endoscopic surgery
      in the prone split-leg position in a single session. CASE PRESENTATION: A 47-year
      old Asian man presented with left flank pain and macrohematuria. The patient had
      undergone left ureteral stenting three years previously for the treatment of left
      ureteral stones and hydronephrosis; however, he was lost to follow-up before the
      treatment for the ureter stones was completed. Therefore, the ureteral stent and
      stones were not removed. An abdominal radiograph and a noncontrast computed
      tomography scan showed encrustation along the retained stent with stone burdens
      in the kidney and ureter. The ureteral stent could not be removed by cystoscopy
      after shock wave lithotripsy of the left ureteral stones. Therefore, endoscopic
      lithotripsy combined with flexible ureteroscopy and miniature nephroscopy was
      performed with the patient in the prone split-leg position. All the stones and
      the encrusted ureteral stent were successfully removed in a single session.
      CONCLUSIONS: In this case, percutaneous nephrolithomy in addition to flexible
      ureteroscopy was preferred because severe encrustation of the proximal stent and
      ureteral stones complicated the therapeutic strategy. Combined endoscopic
      techniques in the prone split-leg position can achieve successful and safe
      management of encrusted stents.

PMID- 24742134
TI  - The role of prothrombin complex concentrates in reversal of target specific
      anticoagulants.
AB  - Over the past several years a new era for patients requiring anticoagulation has
      arrived. The approval of new target specific oral anticoagulants offers
      practitioners several advantages over traditionally used vitamin K antagonist
      agents including predictable pharmacokinetics, rapid onset of action, comparable
      efficacy and safety, all without the need for routine monitoring. Despite these
      benefits, hemorrhagic complicates are inevitable with any anticoagulation
      treatment. One of the major disadvantages of the new oral anticoagulants is lack
      of specific antidotes or reversal agents for patients with serious bleeding or
      need for urgent surgery. As use of the new target specific oral anticoagulants
      continues to increase, practitioners will need to understand both the
      pharmacodynamics and pharmacokinetic properties of the agents, as well as, the
      available literature with use of non-specific therapies to reverse
      anticoagulation. Four factor prothrombin complex concentrates have been available
      for several years in Europe, and recently became available in the United States
      with approval of Kcentra. These products have shown efficacy in reversing
      anticoagulation from vitamin K antagonists, however their usefulness with the new
      target specific oral anticoagulants is poorly understood. This article will
      review the properties of dabigatran, rivaroxaban and apixaban, as well as the
      limited literature available on the effectiveness of prothrombin complex
      concentrates in reversal of their anticoagulant effects. Additional studies are
      needed to more accurately define the role of prothrombin complex concentrates in
      patients with life threatening bleeding or who require emergent surgery, as
      current data is both limited and conflicting. 

PMID- 24742135
TI  - Three-component Pd/Cu-catalyzed cascade reactions of cyclic iodoniums, alkynes,
      and boronic acids: an approach to methylidenefluorenes.
AB  - Linear diaryliodonium salts are widely used as arylating reagents for C-C and C-X
      bond formation. Meanwhile, synthetic applications of cyclic iodoniums are
      relatively rare although they offer the opportunity to set up reaction cascades.
      We demonstrate an atom and step economical three-component reaction involving
      cyclic diphenyleneiodoniums, alkynes, and boronic acids, resulting in the
      construction of methylidenefluorenes in a single operation. Our route enables
      facile access to both symmetrical and unsymmetrical methylidenefluorene
      derivatives, compounds that have attracted interest due to their optical
      properties. 

PMID- 24742136
TI  - Establishing a composite endpoint for measuring the effectiveness of geriatric
      interventions based on older persons' and informal caregivers' preference
      weights: a vignette study.
AB  - BACKGROUND: The Older Persons and Informal Caregivers Survey Minimal Dataset's
      (TOPICS-MDS) questionnaire which measures relevant outcomes for elderly people
      was successfully incorporated into over 60 research projects of the Dutch
      National Care for the Elderly Programme. A composite endpoint (CEP) for this
      instrument would be helpful to compare effectiveness of the various intervention
      projects. Therefore, our aim is to establish a CEP for the TOPICS-MDS
      questionnaire, based on the preferences of elderly persons and informal
      caregivers. METHODS: A vignette study was conducted with 200 persons (124 elderly
      and 76 informal caregivers) as raters. The vignettes described eight TOPICS-MDS
      outcomes of older persons (morbidity, functional limitations, emotional well
      being, pain experience, cognitive functioning, social functioning, self-perceived
      health and self-perceived quality of life) and the raters assessed the general
      well-being (GWB) of these vignette cases on a numeric rating scale (0-10). Mixed
      linear regression analyses were used to derive the preference weights of the
      TOPICS-MDS outcomes (dependent variable: GWB scores; fixed factors: the eight
      outcomes; unstandardized coefficients: preference weights). RESULTS: The mixed
      regression model that combined the eight outcomes showed that the weights varied
      from 0.01 for social functioning to 0.16 for self-perceived health. A model that
      included "informal caregiver" showed that the interactions between this variable
      and each of the eight outcomes were not significant (p > 0.05). CONCLUSION: A
      preference-weighted CEP for TOPICS-MDS questionnaire was established based on the
      preferences of older persons and informal caregivers. With this CEP optimal
      comparing the effectiveness of interventions in older persons can be realized.

PMID- 24742137
TI  - Anticipatory postural adjustments during cutting manoeuvres in football and their
      consequences for knee injury risk.
AB  - Anticipatory postural adjustments (APAs), i.e. preparatory positioning of the
      head, the trunk and the foot, are essential to initiate cutting manoeuvres during
      football games. The aim of the present study was to determine how APA strategies
      during cutting manoeuvres are influenced by a reduction of the time available to
      prepare the movement. Thirteen football players performed different cutting
      tasks, with directions of cutting either known prior to the task or indicated by
      a light signal occurring 850, 600 or 500 ms before ground contact. With less time
      available to prepare the cutting manoeuvre, the head was less orientated towards
      the cutting direction (P = 0.033) and the trunk was even more rotated in the
      opposite direction (P = 0.002), while the foot placement was not significantly
      influenced. Moreover, the induced higher lateral trunk flexion correlated with
      the increased knee abduction moment (r = 0.41; P = 0.009). Increasing lateral
      trunk flexion is the main strategy used to successfully perform a cutting
      manoeuvre when less time is available to prepare the movement. However, higher
      lateral trunk flexion was associated with an increased knee abduction moment and
      therefore an increased knee injury risk. Reducing lateral trunk flexion during
      cutting manoeuvres should be part of training programs seeking the optimisation
      of APAs.

PMID- 24742138
TI  - Lyotropic liquid crystalline nanoparticles of CoQ10: implication of lipase
      digestibility on oral bioavailability, in vivo antioxidant activity, and in vitro
      in vivo relationships.
AB  - The present investigation reports implications of the lipase digestibility of
      lyotropic liquid crystalline nanoparticles (LCNPs) on the oral bioavailability,
      in vivo antioxidant potential, and in vitro-in vivo relationship (IVIVR) of CoQ10
      loaded LCNPs prepared from glyceryl monooleate (GLCQ) and phytantriol (PLCQ).
      Exhaustive optimization of the process variables was carried out, and optimized
      lyophilized formulations were found to have particle sizes of 140.45 +/- 5.47 nm
      and 238.42 +/- 8.35 nm and a polydispersity index (PDI) of 0.15 +/- 0.01 and 0.22
      +/- 0.03 for GLCQ and PLCQ, respectively. The entrapment efficiency at 10%
      theoretical loading was found to be >90% in both the cases. The morphological
      characteristics of the developed formulations were assessed using high resolution
      transmission electron microscopy and small-angle X-ray scattering analysis, which
      showed hexagonal (HII) structure. The developed formulations were also found to
      be stable in simulated gastrointestinal fluids for the stipulated period of time.
      The in vitro drug release studies revealed a bimodal sustained release drug
      profile with Higuchi type release kinetics as the best fit release model for both
      the formulations. The best fit release models were found to be of the Hixson
      Crowell type in the case of GLCQ when carried out in lipase rich media,
      suggestive of matrix erosion and subsequent formation of secondary structures,
      which was further corroborated by carrier degradation studies. Furthermore, 9.1-
      and 10.67-fold increase in Caco-2 cell uptake was observed in the case of GLCQ
      and PLCQ, respectively, attributed to the formation of the virtual channel
      pathway as a probable absorption mechanism. Consequently, 7.09- and 8.67-fold
      increase in oral bioavailability was observed in the case of GLCQ and PLCQ,
      respectively. The IVIVR was also established with r(2) values in the order of
      0.996 and 0.999 for GLCQ and PLCQ, respectively, in contrast to that of 0.484 for
      free CoQ10. Finally, in vivo prophylactic antioxidant efficacy against the STZ
      treated rats using various markers such as GSH, LDH, SOD, MDA, glucose level, and
      body weight showed significantly higher antioxidant activity of CoQ10-LCNPs as
      compared to that of free CoQ10. In a nutshell, the developed formulation strategy
      poses great potential in improving the oral bioavailability of difficult-to
      deliver drugs such as CoQ10. 

PMID- 24742139
TI  - Modelling the effects of media during an influenza epidemic.
AB  - BACKGROUND: Mass media is used to inform individuals regarding diseases within a
      population. The effects of mass media during disease outbreaks have been studied
      in the mathematical modelling literature, by including 'media functions' that
      affect transmission rates in mathematical epidemiological models. The choice of
      function to employ, however, varies, and thus, epidemic outcomes that are
      important to inform public health may be affected. METHODS: We present a survey
      of the disease modelling literature with the effects of mass media. We present a
      comparison of the functions employed and compare epidemic results parameterized
      for an influenza outbreak. An agent-based Monte Carlo simulation is created to
      access variability around key epidemic measurements, and a sensitivity analysis
      is completed in order to gain insight into which model parameters have the
      largest influence on epidemic outcomes. RESULTS: Epidemic outcome depends on the
      media function chosen. Parameters that most influence key epidemic outcomes are
      different for each media function. CONCLUSION: Different functions used to
      represent the effects of media during an epidemic will affect the outcomes of a
      disease model, including the variability in key epidemic measurements. Thus,
      media functions may not best represent the effects of media during an epidemic. A
      new method for modelling the effects of media needs to be considered.

PMID- 24742140
TI  - On InChI and evaluating the quality of cross-reference links.
AB  - BACKGROUND: There are many databases of small molecules focused on different
      aspects of research and its applications. Some tasks may require integration of
      information from various databases. However, determining which entries from
      different databases represent the same compound is not straightforward.
      Integration can be based, for example, on automatically generated cross-reference
      links between entries. Another approach is to use the manually curated links
      stored directly in databases. This study employs well-established InChI
      identifiers to measure the consistency and completeness of the manually curated
      links by comparing them with the automatically generated ones. RESULTS: We used
      two different tools to generate InChI identifiers and observed some ambiguities
      in their outputs. In part, these ambiguities were caused by indistinctness in
      interpretation of the structural data used. InChI identifiers were used
      successfully to find duplicate entries in databases. We found that the InChI
      inconsistencies in the manually curated links are very high (28.85% in the worst
      case). Even using a weaker definition of consistency, the measured values were
      very high in general. The completeness of the manually curated links was also
      very poor (only 93.8% in the best case) compared with that of the automatically
      generated links. CONCLUSIONS: We observed several problems with the InChI tools
      and the files used as their inputs. There are large gaps in the consistency and
      completeness of manually curated links if they are measured using InChI
      identifiers. However, inconsistency can be caused both by errors in manually
      curated links and the inherent limitations of the InChI method.

PMID- 24742141
TI  - The type III protein secretion system contributes to Xanthomonas citri subsp.
      citri biofilm formation.
AB  - BACKGROUND: Several bacterial plant pathogens colonize their hosts through the
      secretion of effector proteins by a Type III protein secretion system (T3SS). The
      role of T3SS in bacterial pathogenesis is well established but whether this
      system is involved in multicellular processes, such as bacterial biofilm
      formation has not been elucidated. Here, the phytopathogen Xanthomonas citri
      subsp. citri (X. citri) was used as a model to gain further insights about the
      role of the T3SS in biofilm formation. RESULTS: The capacity of biofilm formation
      of different X. citri T3SS mutants was compared to the wild type strain and it
      was observed that this secretion system was necessary for this process. Moreover,
      the T3SS mutants adhered proficiently to leaf surfaces but were impaired in leaf
      associated growth. A proteomic study of biofilm cells showed that the lack of the
      T3SS causes changes in the expression of proteins involved in metabolic
      processes, energy generation, exopolysaccharide (EPS) production and bacterial
      motility as well as outer membrane proteins. Furthermore, EPS production and
      bacterial motility were also altered in the T3SS mutants. CONCLUSIONS: Our
      results indicate a novel role for T3SS in X. citri in the modulation of biofilm
      formation. Since this process increases X. citri virulence, this study reveals
      new functions of T3SS in pathogenesis.

PMID- 24742142
TI  - CD4+CD25+/highCD127low/- regulatory T cells are enriched in rheumatoid arthritis
      and osteoarthritis joints--analysis of frequency and phenotype in synovial
      membrane, synovial fluid and peripheral blood.
AB  - INTRODUCTION: CD4+CD25+/highCD127low/- regulatory T cells (Tregs) play a crucial
      role in maintaining peripheral tolerance. Data about the frequency of Tregs in
      rheumatoid arthritis (RA) are contradictory and based on the analysis of
      peripheral blood (PB) and synovial fluid (SF). Because Tregs exert their anti
      inflammatory activity in a contact-dependent manner, the analysis of synovial
      membrane (SM) is crucial. Published reports regarding this matter are lacking, so
      we investigated the distribution and phenotype of Tregs in concurrent samples of
      SM, SF and PB of RA patients in comparison to those of osteoarthritis (OA)
      patients. METHODS: Treg frequency in a total of 40 patients (18 RA and 22 OA)
      matched for age and sex was assessed by flow cytometry. Functional status was
      assessed by analysis of cell surface markers representative of activation, memory
      and regulation. RESULTS: CD4+ T cells infiltrate the SM to higher frequencies in
      RA joints than in OA joints (P = 0.0336). In both groups, Tregs accumulate more
      within the SF and SM than concurrently in PB (P < 0.0001). Relative Treg
      frequencies were comparable in all compartments of RA and OA, but Treg
      concentration was significantly higher in the SM of RA patients (P = 0.025). Both
      PB and SM Tregs displayed a memory phenotype (CD45RO+RA-), but significantly
      differed in activation status (CD69 and CD62L) and markers associated with Treg
      function (CD152, CD154, CD274, CD279 and GITR) with only minor differences
      between RA and OA. CONCLUSIONS: Treg enrichment into the joint compartment is not
      specific to inflammatory arthritis, as we found that it was similarly enriched in
      OA. RA pathophysiology might not be due to a Treg deficiency, because Treg
      concentration in SM was significantly higher in RA. Synovial Tregs represent a
      distinct phenotype and are activated effector memory cells (CD62L-CD69+), whereas
      peripheral Tregs are resting central memory cells (CD62L+CD69-).

PMID- 24742143
TI  - Cognitively elite, cognitively normal, and cognitively impaired aging:
      neurocognitive status and stability moderate memory performance.
AB  - OBJECTIVE: Although recent theories of brain and cognitive aging distinguish
      between normal, exceptional, and impaired groups, further empirical evidence is
      required. We adapted and applied standard procedures for classifying groups of
      cognitively impaired (CI) and cognitively normal (CN) older adults to a third
      classification: cognitively healthy, exceptional, or elite (CE) aging. We then
      examined concurrent and two-wave longitudinal performance on composite variables
      of episodic, semantic, and working memory. METHOD: We began with a two-wave
      source sample from the Victoria Longitudinal Study (VLS; source n = 570; baseline
      age = 53-90 years). The goals were to: (a) apply standard and objective
      classification procedures to discriminate three cognitive status groups, (b)
      conduct baseline comparisons of memory performance, (c) develop two-wave status
      stability and change subgroups, and (d) compare of stability subgroup differences
      in memory performance and change. RESULTS: As expected, the CE group performed
      best on all three memory composites. Similarly, expected status stability effects
      were observed: (a) stable CE and CN groups performed memory tasks better than
      their unstable counterparts, and (b) the stable (and chronic) CI group performed
      worse than its unstable (variable) counterpart. These stability group differences
      were maintained over two waves. CONCLUSION: New data validate the expectations
      that (a) objective clinical classification procedures for cognitive impairment
      can be adapted for detecting cognitively advantaged older adults, and (b)
      performance in three memory systems is predictably related to the tripartite
      classification.

PMID- 24742145
TI  - Investigation of the genetic diversity of domestic Capra hircus breeds reared
      within an early goat domestication area in Iran.
AB  - BACKGROUND: Iran is an area of particular interest for investigating goat
      diversity. Archaeological remains indicate early goat domestication (about 10,000
      years ago) in the Iranian Zagros Mountains as well as in the high Euphrates
      valley and southeastern Anatolia. In addition, mitochondrial DNA data of domestic
      goats and wild ancestors (C. aegagrusor bezoar) suggest a pre-domestication
      management of wild populations in southern Zagros and central Iranian Plateau. In
      this study genetic diversity was assessed in seven Iranian native goat breeds,
      namely Markhoz, Najdi, Taleshi, Khalkhali, Naini, native Abadeh and Turki
      Ghashghaei. A total of 317 animals were characterized using 14 microsatellite
      loci. Two Pakistani goat populations, Pahari and Teddy, were genotyped for
      comparison. RESULTS: Iranian goats possess a remarkable genetic diversity
      (average expected heterozygosity of 0.671 across loci, 10.7 alleles per locus)
      mainly accounted for by the within-breed component (GST = 5.9%). Positive and
      highly significant FIS values in the Naini, Turki-Ghashghaei, Abadeh and Markhoz
      breeds indicate some level of inbreeding in these populations. Multivariate
      analyses cluster Iranian goats into northern, central and western groups, with
      the western breeds relatively distinct from the others. Pakistani breeds show
      some relationship with Iranian populations, even if their position is not
      consistent across analyses. Gene flow was higher within regions (west, north,
      central) compared to between regions but particularly low between the western and
      the other two regions, probably due to the isolating topography of the Zagros
      mountain range. The Turki-Ghashghaei, Najdi and Abadeh breeds are reared in
      geographic areas where mtDNA provided evidence of early domestication. These
      breeds are highly variable, located on basal short branches in the neighbor
      joining tree, close to the origin of the principal component analysis plot and,
      although highly admixed, they are quite distinct from those reared on the western
      side of the Zagros mountain range. CONCLUSIONS: These observations call for
      further investigation of the nuclear DNA diversity of these breeds within a much
      wider geographic context to confirm or re-discuss the current hypothesis (based
      on maternal lineage data) of an almost exclusive contribution of the eastern
      Anatolian bezoar to the domestic goat gene pool.

PMID- 24742146
TI  - The effectiveness of Tai Chi on the physical and psychological well-being of
      college students: a study protocol for a randomized controlled trial.
AB  - BACKGROUND: The physical and mental health of college-age youths tends to
      continuously decline around the world. It is therefore important to promote
      health during this period. As a traditional Chinese mind-body exercise, Tai Chi
      Chuan (TCC) may be an available selection. However for the college student
      population, the evidence is unclear as to whether TCC can be recommended as an
      effective exercise for promoting their physical and psychological wellbeing.
      Therefore high quality, rigorous, prospective, and well-controlled randomized
      trials are needed to further understand TCC serving as a psychological and
      physical intervention in college age populations. METHOD/DESIGN: We designed a
      randomized, single-blind, parallel-controlled trial with a sample size of 206
      participants. All the participants who meet the inclusion criteria come from
      Fujian University of Traditional Chinese Medicine (FJTCM). Participants of the
      TCC training group will receive TCC training at a frequency of five days per week
      for one hour per day for 12 weeks. No specific exercise will be administered on
      the participants in the control group. Both physical and mental health outcomes,
      including balance ability, lower limb proprioception, flexibility, physical
      fitness, self-efficacy, psychological symptoms, attention span, stress, self
      esteem, mood and mindfulness, quality of life, and quality of sleep. Safety
      outcomes will be evaluated by blinded operators at baseline, 12 and 24-weeks post
      intervention. DISCUSSION: This protocol presents an objective design of a
      randomized, single-blind trial that will test the effectiveness and safety of TCC
      on the physical and psychological wellbeing of college students. If the outcome
      is positive, the results will provide higher quality evidence of TCC on the
      physical and mental health of college age populations. TRIAL REGISTRATION:
      Chinese Clinical Trial Registry: ChiCTR-TRC-13003328.

PMID- 24742149
TI  - Multicompartment lipid cubic nanoparticles with high protein upload: millisecond
      dynamics of formation.
AB  - Membrane shapes, produced by dynamically assembled lipid/protein architectures,
      are crucial for both physiological functions and the design of therapeutic
      nanotechnologies. Here we investigate the dynamics of lipid membrane-neurotrophic
      BDNF protein complexes formation and ordering in nanoparticles, with the purpose
      of innovation in nanostructure-based neuroprotection and biomimetic
      nanoarchitectonics. The kinetic pathway of membrane states associated with
      rapidly occurring nonequilibrium self-assembled lipid/protein nanoarchitectures
      was determined by millisecond time-resolved small-angle X-ray scattering (SAXS)
      at high resolution. The neurotrophin binding and millisecond trafficking along
      the flexible membranes induced an unusual overlay of channel-network
      architectures including two coexisting cubic lattices epitaxially connected to
      lamellar membrane stacks. These time-resolved membrane processes, involving
      intercalation of discrete stiff proteins in continuous soft membranes, evidence
      stepwise curvature control mechanisms. The obtained three-phase liquid
      crystalline nanoparticles of neurotrophic composition put forward important
      advancements in multicompartment soft-matter nanostructure design. 

PMID- 24742150
TI  - Synthesis and evaluation of phosphorus containing, specific CDK9/CycT1
      inhibitors.
AB  - Although there is a significant effort in the design of a selective CDK9/CycT1
      inhibitor, no compound has been proven to be a specific inhibitor of this kinase
      so far. The aim of this research was to develop novel and selective phosphorus
      containing CDK9/CycT1 inhibitors. Molecules bearing phosphonamidate, phosphonate,
      and phosphinate moieties were synthesized. Prepared compounds were evaluated in
      an enzymatic CDK9/CycT1 assay. The most potent molecules were tested in cell
      based toxicity and HIV proliferation assays. Selectivity of shortlisted compounds
      against CDKs and other kinases was tested. The best compound was shown to be a
      highly specific, ATP-competitive inhibitor of CDK9/CycT1 with antiviral activity.

PMID- 24742151
TI  - InGaN/GaN core-shell single nanowire light emitting diodes with graphene-based p
      contact.
AB  - We report on the demonstration of MOVPE-grown single nanowire InGaN/GaN core
      shell light emitting diodes (LEDs) with a transparent graphene contact for hole
      injection. The electrical homogeneity of the graphene-contacted LED has been
      assessed by electron beam induced current microscopy. By comparing graphene
      contacted and metal-contacted nanowire LEDs, we show that the contact layout
      determines the electroluminescence spectrum. The electroluminescence changes
      color from green to blue with increasing injection current. High-resolution
      cathodoluminescence on cleaved nanowires allows the location with high precision
      of the origin of different emitted wavelengths and demonstrates that the blue
      peak originates from the emission of the radial quantum well on the m-planes,
      whereas the green peak arises from the In-rich region at the junction between the
      m-planes and the semipolar planes. The spectral behavior of the
      electroluminescence is understood by modeling the current distribution within the
      nanowire. 

PMID- 24742152
TI  - Analysis of football game-related statistics using multivariate techniques.
AB  - Abstract The purpose of this study was to explore football game-related
      statistics during a competition, using principal component and cluster analyses
      to determine if it is possible to distinguish the winning teams from the drawing
      and losing ones. We collected the game-related statistics of the group phase
      matches of the 2006 World Cup and organised them into a matrix. The principal
      components of the covariance matrix were calculated. The scores of the first and
      second components were used to represent the new data, and cluster analysis was
      applied to separate the elements in two groups (G1 and G2). To analyse the degree
      of separation between the groups, we calculated the Silhouette Coefficient for
      each group. Finally, we checked if the winning teams were classified into the
      same group. The Silhouette Coefficients found for G1 and G2 were 0.54 and 0.55,
      respectively. Results showed that 70.3% of the winning teams were classified into
      the same group (G1). Similarly, 67.8% of the drawing and losing teams were
      classified in G2. This study presented a different way to analyse game-related
      statistics that allowed the multivariate differences to be shown between
      successful and unsuccessful teams.

PMID- 24742153
TI  - Predictors of response to steroid therapy in patients with acute, severe
      ulcerative colitis.

PMID- 24742154
TI  - Contact with child and adolescent psychiatric services among self-harming and
      suicidal adolescents in the general population: a cross sectional study.
AB  - BACKGROUND: Studies have shown that adolescents with a history of both suicide
      attempts and non-suicidal self-harm report more mental health problems and other
      psychosocial problems than adolescents who report only one or none of these types
      of self-harm. The current study aimed to examine the use of child and adolescent
      psychiatric services by adolescents with both suicide attempts and non-suicidal
      self-harm, compared to other adolescents, and to assess the psychosocial
      variables that characterize adolescents with both suicide attempts and non
      suicidal self-harm who report contact. METHODS: Data on lifetime self-harm,
      contact with child and adolescent psychiatric services, and various psychosocial
      risk factors were collected in a cross-sectional sample (response rate = 92.7%)
      of 11,440 adolescents aged 14-17 years who participated in a school survey in
      Oslo, Norway. RESULTS: Adolescents who reported any self-harm were more likely
      than other adolescents to have used child and adolescent psychiatric services,
      with a particularly elevated likelihood among those with both suicide attempts
      and non-suicidal self-harm (OR = 9.3). This finding remained significant even
      when controlling for psychosocial variables. In adolescents with both suicide
      attempts and non-suicidal self-harm, symptoms of depression, eating problems, and
      the use of illicit drugs were associated with a higher likelihood of contact with
      child and adolescent psychiatric services, whereas a non-Western immigrant
      background was associated with a lower likelihood. CONCLUSIONS: In this study,
      adolescents who reported self-harm were significantly more likely than other
      adolescents to have used child and adolescent psychiatric services, and
      adolescents who reported a history of both suicide attempts and non-suicidal self
      harm were more likely to have used such services, even after controlling for
      other psychosocial risk factors. In this high-risk subsample, various
      psychosocial problems increased the probability of contact with child and
      adolescent psychiatric services, naturally reflecting the core tasks of the
      services, confirming that they represents an important area for interventions
      that aim to reduce self-harming behaviour. Such interventions should include
      systematic screening for early recognition of self-harming behaviours, and
      treatment programmes tailored to the needs of teenagers with a positive screen.
      Possible barriers to receive mental health services for adolescents with
      immigrant backgrounds should be further explored.

PMID- 24742156
TI  - Prestimulus neural oscillations inhibit visual perception via modulation of
      response gain.
AB  - The ongoing state of the brain radically affects how it processes sensory
      information. How does this ongoing brain activity interact with the processing of
      external stimuli? Spontaneous oscillations in the alpha range are thought to
      inhibit sensory processing, but little is known about the psychophysical
      mechanisms of this inhibition. We recorded ongoing brain activity with EEG while
      human observers performed a visual detection task with stimuli of different
      contrast intensities. To move beyond qualitative description, we formally
      compared psychometric functions obtained under different levels of ongoing alpha
      power and evaluated the inhibitory effect of ongoing alpha oscillations in terms
      of contrast or response gain models. This procedure opens the way to
      understanding the actual functional mechanisms by which ongoing brain activity
      affects visual performance. We found that strong prestimulus occipital alpha
      oscillations-but not more anterior mu oscillations-reduce performance most
      strongly for stimuli of the highest intensities tested. This inhibitory effect is
      best explained by a divisive reduction of response gain. Ongoing occipital alpha
      oscillations thus reflect changes in the visual system's input/output
      transformation that are independent of the sensory input to the system. They
      selectively scale the system's response, rather than change its sensitivity to
      sensory information. 

PMID- 24742155
TI  - All competition is not alike: neural mechanisms for resolving underdetermined and
      prepotent competition.
AB  - People must constantly select among potential thoughts and actions in the face of
      competition from (a) multiple task-relevant options (underdetermined competition)
      and (b) strongly dominant options that are not appropriate in the current context
      (prepotent competition). These types of competition are ubiquitous during
      language production. In this work, we investigate the neural mechanisms that
      allow individuals to effectively manage these cognitive control demands and to
      quickly choose words with few errors. Using fMRI, we directly contrast
      underdetermined and prepotent competition within the same task (verb generation)
      for the first time, allowing localization of the neural substrates supporting the
      resolution of these two types of competition. Using a neural network model, we
      investigate the possible mechanisms by which these brain regions support
      selection. Together, our findings demonstrate that all competition is not alike:
      resolving prepotent competition and resolving underdetermined competition rely on
      partly dissociable neural substrates and mechanisms. Specifically, activation of
      left ventrolateral pFC is specific to resolving underdetermined competition
      between multiple appropriate responses, most likely via competitive lateral
      inhibition. In contrast, activation of left dorsolateral pFC is sensitive to both
      underdetermined competition and prepotent competition from response options that
      are inappropriate in the current context. This region likely provides top-down
      support for task-relevant responses, which enables them to out-compete prepotent
      responses in the selection process that occurs in left ventrolateral pFC. 

PMID- 24742157
TI  - The control of automatic imitation based on bottom-up and top-down cues to
      animacy: insights from brain and behavior.
AB  - Humans automatically imitate other people's actions during social interactions,
      building rapport and social closeness in the process. Although the behavioral
      consequences and neural correlates of imitation have been studied extensively,
      little is known about the neural mechanisms that control imitative tendencies.
      For example, the degree to which an agent is perceived as human-like influences
      automatic imitation, but it is not known how perception of animacy influences
      brain circuits that control imitation. In the current fMRI study, we examined how
      the perception and belief of animacy influence the control of automatic
      imitation. Using an imitation-inhibition paradigm that involves suppressing the
      tendency to imitate an observed action, we manipulated both bottom-up (visual
      input) and top-down (belief) cues to animacy. Results show divergent patterns of
      behavioral and neural responses. Behavioral analyses show that automatic
      imitation is equivalent when one or both cues to animacy are present but reduces
      when both are absent. By contrast, right TPJ showed sensitivity to the presence
      of both animacy cues. Thus, we demonstrate that right TPJ is biologically tuned
      to control imitative tendencies when the observed agent both looks like and is
      believed to be human. The results suggest that right TPJ may be involved in a
      specialized capacity to control automatic imitation of human agents, rather than
      a universal process of conflict management, which would be more consistent with
      generalist theories of imitative control. Evidence for specialized neural
      circuitry that "controls" imitation offers new insight into developmental
      disorders that involve atypical processing of social information, such as autism
      spectrum disorders. 

PMID- 24742159
TI  - Aminative umpolung synthesis of aryl vicinal diamines from aromatic aldehydes.
AB  - In this paper an aminative umpolung synthesis of aryl vicinal diamines from
      aldehydes and N-Ts imines is described. Electrophilic aromatic aldehydes were
      smoothly converted into delocalized 2-azaallylanions via condensation with 2,2
      diphenylglycine in methanol and subsequent decarboxylation in THF and underwent
      further reaction with N-Ts imines to give a variety of 1,2-diamine derivatives in
      good yields with high syn/anti diastereoselectivity. 

PMID- 24742158
TI  - Cost-outcome description of clinical pharmacist interventions in a university
      teaching hospital.
AB  - BACKGROUND: Pharmacist interventions are one of the pivotal parts of a clinical
      pharmacy service within a hospital. This study estimates the cost avoidance
      generated by pharmacist interventions due to the prevention of adverse drug
      events (ADE). The types of interventions identified are also analysed. METHODS:
      Interventions recorded by a team of hospital pharmacists over a one year time
      period were included in the study. Interventions were assigned a rating score,
      determined by the probability that an ADE would have occurred in the absence of
      an intervention. These scores were then used to calculate cost avoidance. Net
      cost benefit and cost benefit ratio were the primary outcomes. Categories of
      interventions were also analysed. RESULTS: A total cost avoidance of ?708,221 was
      generated. Input costs were calculated at ?81,942. This resulted in a net cost
      benefit of ?626,279 and a cost benefit ratio of 8.64: 1. The most common type of
      intervention was the identification of medication omissions, followed by dosage
      adjustments and requests to review therapies. CONCLUSION: This study provides
      further evidence that pharmacist interventions provide substantial cost avoidance
      to the healthcare payer. There is a serious issue of patient's regular medication
      being omitted on transfer to an inpatient setting in Irish hospitals.

PMID- 24742160
TI  - Fe-catalyzed novel domino isomerization/cyclodehydration of substituted 2
      [(indoline-3-ylidene)(methyl)]benzaldehyde derivatives: an efficient approach
      toward benzo[b]carbazole derivatives.
AB  - A new and efficient protocol to synthesize substituted benzo[b]carbazole
      derivatives has been demonstrated involving iron-catalyzed domino
      isomerization/cyclodehydration sequences from substituted 2-[(indoline-3
      ylidene)(methyl)]benzaldehyde derivatives. The substrates could be easily made
      via Pd-catalyzed domino Heck-Suzuki coupling from 2-bromo-N-propargylanilide
      derivatives in high yields. Notably, the generality and efficiency of this two
      stage domino strategy was further exemplified by the synthesis of a polycyclic
      benzofuran derivative. 

PMID- 24742161
TI  - Synthesis of arylglycines from CO2 through alpha-amino organomanganese species.
AB  - In the presence of three readily available chemicals, Mn powder, BF3.OEt2, and
      LiCl, N-acyl-N,O-acetals were successfully converted into the corresponding alpha
      amino acids (arylglycine derivatives) under 1 atm of a CO2 atmosphere in high
      yields. The LiCl additive is necessary in order to increase the solubility and
      the nucleophilicity of an organomanganese intermediate. The products thus
      obtained were transformed into free alpha-amino acids in two steps. 

PMID- 24742162
TI  - Formal synthesis of actin binding macrolide rhizopodin.
AB  - Formal synthesis of an actin binding macrolide rhizopodin was achieved in 19
      longest linear steps. The key features of the synthesis include a stereoselective
      Mukaiyama aldol reaction, dual role of a Nagao auxiliary (first, as a chiral
      auxiliary of choice for installing hydroxy centers and, later, as an acylating
      agent to form an amide bond with an amino alcohol), late stage oxazole formation,
      and Stille coupling reactions. 

PMID- 24742163
TI  - Stereocontrolled construction of the tricyclic framework of tiglianes and
      daphnanes by an oxidative dearomatization approach.
AB  - An appropriately functionalized [5-7-6] tricyclic framework of tigliane and
      daphnane diterpenes containing seven contiguous stereocenters has been prepared
      in 10 steps from very simple building blocks in a modular and stereocontrolled
      fashion. The key features of this approach involve an efficient visible light
      induced singlet oxygen oxidative dearomatization and an array of substrate
      controlled highly diastereoselective transformations. This work provides a model
      strategy for rapid and diverted synthesis of natural and unnatural molecules
      sharing the common skeleton. 

PMID- 24742166
TI  - Industrial air pollution in rural Kenya: community awareness, risk perception and
      associations between risk variables.
AB  - BACKGROUND: Developing countries have limited air quality management systems due
      to inadequate legislation and lack of political will, among other challenges.
      Maintaining a balance between economic development and sustainable environment is
      a challenge, hence investments in pollution prevention technologies get sidelined
      in favor of short-term benefits from increased production and job creation. This
      lack of air quality management capability translates into lack of air pollution
      data, hence the false belief that there is no problem. The objectives of the
      study were to: assess the population's environmental awareness, explore their
      perception of pollution threat to their health; examine the association between
      specific health hazards. METHODS: A cross-sectional study was implemented by
      gathering quantitative information on demographic, health status, environmental
      perception and environmental knowledge of residents to understand their view of
      pollution in their neighborhood. Focus group discussions (FGDs) allowed for
      corroboration of the quantitative data. RESULTS: Over 80% of respondents
      perceived industrial pollution as posing a considerable risk to them despite the
      fact that the economy of the area largely depended on the factory. Respondents
      also argued that they had not been actively involved in identifying solutions to
      the environmental challenges. The study revealed a significant association
      between industrial pollution as a risk and, perception of risk from other
      familiar health hazards. The most important factors influencing the respondents'
      pollution risk perception were environmental awareness and family health status.
      CONCLUSION: This study avails information to policy makers and researchers
      concerning public awareness and attitudes towards environmental pollution
      pertinent to development and implementation of environmental policies for public
      health.

PMID- 24742168
TI  - E-assessment of prior learning: a pilot study of interactive assessment of staff
      with no formal education who are working in Swedish elderly care.
AB  - BACKGROUND: The current paper presents a pilot study of interactive assessment
      using information and communication technology (ICT) to evaluate the knowledge,
      skills and abilities of staff with no formal education who are working in Swedish
      elderly care. METHODS: Theoretical and practical assessment methods were
      developed and used with simulated patients and computer-based tests to identify
      strengths and areas for personal development among staff with no formal
      education. RESULTS: Of the 157 staff with no formal education, 87 began the
      practical and/or theoretical assessments, and 63 completed both assessments.
      Several of the staff passed the practical assessments, except the morning hygiene
      assessment, where several failed. Other areas for staff development, i.e. where
      several failed (>50%), were the theoretical assessment of the learning
      objectives: Health, Oral care, Ergonomics, hygiene, esthetic, environmental,
      Rehabilitation, Assistive technology, Basic healthcare and Laws and organization.
      None of the staff passed all assessments. Number of years working in elderly care
      and staff age were not statistically significantly related to the total score of
      grades on the various learning objectives. CONCLUSION: The interactive
      assessments were useful in assessing staff members' practical and theoretical
      knowledge, skills, and abilities and in identifying areas in need of development.
      It is important that personnel who lack formal qualifications be clearly
      identified and given a chance to develop their competence through training, both
      theoretical and practical. The interactive e-assessment approach analyzed in the
      present pilot study could serve as a starting point.

PMID- 24742167
TI  - The next step in health behavior research: the need for ecological moderation
      analyses - an application to diet and physical activity at childcare.
AB  - BACKGROUND: The ecological perspective holds that human behavior depends on the
      interaction of different environmental factors and personal characteristics, but
      it lacks validation and operationalization. In the current paper, an ecological
      view was adopted to examine the interactive impact of several ecological systems
      on children's dietary intake and physical activity at childcare or similar
      facilities. The ecological view was operationalized into three types of
      interaction: 1) interaction between types of childcare environment (physical,
      social, political, economic); 2) interaction between micro-systems (the childcare
      and home environment) in meso-systems; and 3) interaction between childcare
      environment and child characteristics. The predictive value of each of these
      interactions was tested based on a systematic review of the literature.
      DISCUSSION: Several studies support the hypothesis that the influence of the
      childcare environment on children's physical activity and diet is moderated by
      child characteristics (age, gender), but interaction between environmental types
      as well as between micro-systems is hardly examined in the field of behavioral
      nutrition and physical activity. Qualitative studies and general child
      development research provide some valuable insights, but we advocate quantitative
      research adopting an ecological perspective on environmental influences. SUMMARY:
      Empirical studies operationalizing a true ecological view on diet and physical
      activity are scarce. Theorizing and assessment of interaction is advocated to
      become common practice rather than an exception in behavioral nutrition and
      physical activity research, in order to move the field forward.

PMID- 24742169
TI  - A systematic review of therapeutic hypothermia for adult patients following
      traumatic brain injury.
AB  - INTRODUCTION: Research into therapeutic hypothermia following traumatic brain
      injury has been characterised by small trials of poor methodological quality,
      producing variable results. The Cochrane review, published in 2009, now requires
      updating. The aim of this systematic review is to assess the effectiveness of the
      application of therapeutic hypothermia to reduce death and disability when
      administered to adult patients who have been admitted to hospital following
      traumatic brain injury. METHODS: Two authors extracted data from each trial.
      Unless stated in the trial report, relative risks and 95% confidence intervals
      (CIs) were calculated for each trial. We considered P < 0 . 05 to be
      statistically significant. We combined data from all trials to estimate the
      pooled risk ratio (RR) with 95% confidence intervals for death, unfavourable
      outcome, and pneumonia. All statistical analyses were performed using RevMan 5.1
      (Cochrane IMS, Oxford, UK) and Stata (Intercooled Version 12.0, StataCorp LP).
      Pooled RRs were calculated using the Mantel-Haenszel estimator. The random
      effects model of DerSimonian and Laird was used to estimate variances for the
      Mantel-Haenszel and inverse variance estimators. RESULTS: Twenty studies are
      included in the review, while 18 provided mortality data. When the results of 18
      trials that evaluated mortality as one of the outcomes were statistically
      aggregated, therapeutic hypothermia was associated with a significant reduction
      in mortality and a significant reduction in poor outcome. There was a lack of
      statistical evidence for an association between use of therapeutic hypothermia
      and increased onset of new pneumonia. CONCLUSIONS: In contrast to previous
      reviews, this systematic review found some evidence to suggest that therapeutic
      hypothermia may be of benefit in the treatment of traumatic brain injury. The
      majority of trials were of low quality, with unclear allocation concealment. Low
      quality trials may overestimate the effectiveness of hypothermia treatment versus
      standard care. There remains a need for more, high quality, randomised control
      trials of therapeutic hypothermia after traumatic brain injury.

PMID- 24742170
TI  - Stability of intraindividual variability as a marker of neurologic dysfunction in
      relapsing remitting multiple sclerosis.
AB  - BACKGROUND: Impairments in information processing speed are common in multiple
      sclerosis (MS), with affected individuals demonstrating slower responses and more
      intraindividual variability (IIV) in their performance on timed tasks. Evidence
      suggesting that IIV provides novel information about cognitive deficits in MS is
      accumulating; however, little is known about the stability of IIV across multiple
      assessments. In this study, we investigated IIV in response speed in persons with
      MS across 6 monthly sessions using the Attention Network Test-Interaction (ANT
      I). METHOD: Individuals with relatively mild relapsing remitting MS and healthy
      controls completed the ANT-I at 6 monthly intervals. Clinical assessments
      (Sessions 1 and 6) and conventional magnetic resonance imaging (MRI) studies
      (Sessions 1-6) were examined for individuals with MS. RESULTS: The MS group's
      clinical and neuroimaging measures were stable during the 6-month period.
      Individuals with MS were slower and more variable in reaction time performance on
      the ANT-I than were controls. Differences in IIV between groups were maintained
      across the 6 sessions, with IIV demonstrating less susceptibility to across
      session practice effects than mean latency scores. CONCLUSIONS: IIV provides a
      stable measure of cognitive performance in mildly affected persons with MS who
      are clinically and radiologically stable. Further studies exploring its utility
      as a clinical outcome are warranted.

PMID- 24742171
TI  - Performance of lung ultrasonography in children with community-acquired
      pneumonia.
AB  - BACKGROUND: There are few prospective evaluations of point-of-care
      ultrasonography (US) for the diagnosis of pediatric community-acquired pneumonia
      (CAP). In particular, there are very few data concerning the efficiency of US in
      comparison with that of chest radiography (CR) in defining different kinds of
      lung alterations in the various pulmonary sections. The aim of this study was to
      bridge this gap in order to increase our knowledge of the performance of US in
      diagnosing CAP in childhood. METHODS: A total of 103 children (56 males, 54.4%;
      mean age +/- standard deviation 5.6 +/- 4.6 years) admitted to hospital with a
      clinical diagnosis of suspected CAP were prospectively enrolled and underwent CR
      (evaluated by an independent expert radiologist) and lung US (performed by a
      resident in paediatrics with limited experience in US). The performance of US in
      diagnosing CAP (i.e. its sensitivity, specificity, and positive and negative
      predictive values) was compared with that of CR. RESULTS: A total of 48 patients
      had radiographically confirmed CAP. The sensitivity, specificity, and positive
      and negative predictive values of US in comparison with CR were respectively
      97.9%, 94.5%, 94.0% and 98.1%. US identified a significantly higher number of
      cases of pleural effusion, but the concordance of the two methods in identifying
      the type of CAP was poor. CONCLUSION: US can be considered a useful means of
      diagnosing CAP in children admitted to an Emergency Department with a lower
      respiratory tract infection, although its usefulness in identifying the type of
      lung involvement requires further evaluation.

PMID- 24742172
TI  - Long-acting reversible contraception for adolescents and young adults - a cross
      sectional study of women and general practitioners in Oslo, Norway.
AB  - OBJECTIVES: To investigate awareness and use of long-acting reversible
      contraceptives (LARCs) in the Norwegian primary care sector. METHODS: We surveyed
      359 women aged 16 to 23 years visiting a free sexual health clinic and 140
      general practitioners (GPs) in Oslo, Norway, to assess contraceptive usage
      patterns, knowledge, opinions, and counselling content. RESULTS: Eighty-two
      percent (n = 295) of the female respondents were current contraceptive users and
      of this group, 12% (n = 34) were LARC users. Combined oral contraceptives (COCs,
      56%) and condoms (20%) were the methods most commonly used. Apart from those two,
      the women considered themselves insufficiently knowledgeable about other family
      planning modalities. Knowledge was an independent predictor of current LARC use
      (p < 0.001). Approximately 35% of GPs often discussed LARC methods when
      counselling but, due to a lack of implant insertion training, only a few
      frequently discussed implants during counselling (odds ratio [OR]: 0.12; p =
      0.013). The main determinant for not mentioning intrauterine devices and the
      intrauterine system during counselling was nulliparity (OR: 0.2; p = 0.001 and <
      0.001, respectively). CONCLUSION: LARC use is low among 16 to 23-year-olds in
      Oslo, Norway. These young women need better contraceptive counselling. Dispelling
      misconceptions and improved provider training could encourage GPs to cover LARCs
      when giving contraceptive guidance.

PMID- 24742174
TI  - A mixed population of antagonist and agonist binding conformers in a single
      crystal explains partial agonism against vitamin D receptor: active vitamin D
      analogues with 22R-alkyl group.
AB  - We are continuing to study the structural basis of vitamin D receptor (VDR)
      agonism and antagonism by using 22S-alkyl vitamin D analogues. Here we report the
      synthesis and biological evaluation of 22R-alkyl analogues and the X-ray
      crystallographic analysis of vitamin D receptor ligand-binding domain (VDR-LBD)
      complexed with a 22R-analogue. VDR-LBD complexed with the partial agonist 8a
      showed that 8a binds to VDR-LBD with two conformations, one of which is the
      antagonist/VDR-LBD complex structure and the other is the agonist/VDR-LBD complex
      structure. The results indicate that the partial agonist activity of 8a depends
      on the sum of antagonistic and agonistic activities caused by the antagonist and
      agonist binding conformers, respectively. The structural basis observed here must
      be applicable to the partial agonism of other ligand-dependent nuclear receptors.
      This is the first report describing the trapping of a conformational subset of
      the ligand and the nuclear receptor in a single crystal. 

PMID- 24742173
TI  - Molecular characterization of cytolethal distending toxin gene-positive
      Escherichia coli from healthy cattle and swine in Nara, Japan.
AB  - BACKGROUND: Cytolethal distending toxin (CDT)-producing Escherichia coli (CTEC)
      has been isolated from patients with gastrointestinal or urinary tract infection,
      and sepsis. However, the source of human infection remains unknown. In this
      study, we attempted to detect and isolate CTEC strains from fecal specimens of
      healthy farm animals and characterized them phenotypically and genotypically.
      RESULTS: By PCR analysis, the cdtB gene was detected in 90 and 14 out of 102 and
      45 stool specimens of healthy cattle and swine, respectively, and none from 45
      chicken samples. Subtypes of the cdtB genes (I to V) were further examined by
      restriction fragment length polymorphism analysis of the amplicons and by type
      specific PCRs for the cdt-III and cdt-V genes. Of the 90 cdtB gene-positive
      cattle samples, 2 cdt-I, 25 cdt-III, 1 cdt-IV, 52 cdt-V and 1 both cdt-III and
      cdt-V gene-positive strains were isolated while 1 cdt-II and 6 cdt-V gene
      positive were isolated from 14 cdtB positive swine samples. Serotypes of some
      isolates were identical to those of human isolates. Interestingly, a cdt-II gene
      positive strain isolated from swine was for the first time identified as
      Escherichia albertii. Phylogenetic analysis grouped 87 E. coli strains into 77
      phylogroup B1, 6 B2, and 4 D, respectively. Most of the B1 strains harbored both
      lpfAO113 and ehaA. Three and twenty-two cdt-V gene-positive strains harbored eaeA
      and stx genes, respectively, and seven possessed cdt-V, stx and subAB genes. The
      cnf2 gene, normally present in cdt-III gene-positive strains, was also detected
      in cdt-V gene-positive strains. CONCLUSIONS: Our results suggest that healthy
      cattle and swine could be the reservoir of CTEC, and they could be a potential
      source of human infections.

PMID- 24742175
TI  - The normal neuroendocrine cells of the upper gastrointestinal tract lack E
      cadherin.
AB  - OBJECTIVE: E-cadherin plays a crucial role in the adhesion between epithelial
      cells and thus epithelial integrity. Moreover, germline mutations in the E
      cadherin gene (CDH1) causing loss of E-cadherin function (adhesion) leads to
      hereditary gastric cancer of the diffuse type, according to Lauren. Even sporadic
      gastric carcinomas of the diffuse type often lose E-cadherin expression due to
      mutations. Lack of E-cadherin has been recorded at an early phase in such
      carcinomas. For 25 years, we have provided evidence for neuroendocrine (NE) cell
      origin of gastric carcinomas of diffuse type. The present study was, therefore,
      done to examine whether normal NE cells in the gastrointestinal tract express E
      cadherin or not. METHODS: During upper gastrointestinal endoscopy, biopsies were
      taken from normal oxyntic mucosa, gastric carcinoids, gastric carcinomas, and
      from normal duodenal mucosa. Tissues were examined by immunohistochemistry (IHC)
      using antibodies toward chromogranin A, synaptophysin, and E-cadherin. Isolated
      mucosal cells were prepared from biopsies of normal mucosa and examined by
      antibodies against the same markers by immunofluorescence. RESULTS: Normal
      gastrointestinal NE cells did not express E-cadherin as assessed by IHC or
      immunocytochemistry. No expression of E-cadherin was found on tumor cells from
      gastric carcinoids or cancer of diffuse type examined by IHC. CONCLUSION: Our
      findings, which are in contrast to some previous studies, may explain why there
      is a discrepancy between lack of atypia and malignant biological behavior of such
      tumors. Since they normally lack the adhesion molecule E-cadherin, reflected in
      their spread occurrence, only minor changes may result in malignant behavior.

PMID- 24742176
TI  - Cell-cell communication special issue.

PMID- 24742179
TI  - d-OptCom: Dynamic multi-level and multi-objective metabolic modeling of microbial
      communities.
AB  - Most microbial communities change with time in response to changes and/or
      perturbations in environmental conditions. Temporal variations in interspecies
      metabolic interactions within these communities can significantly affect their
      structure and function. Here, we introduce d-OptCom, an extension of the OptCom
      procedure, for the dynamic metabolic modeling of microbial communities. It
      enables capturing the temporal dynamics of biomass concentration of the community
      members and extracellular concentration of the shared metabolites, while
      integrating species- and community-level fitness functions. The applicability of
      d-OptCom was demonstrated by modeling the dynamic co-growth of auxotrophic mutant
      pairs of E. coli and by computationally assessing the dynamics and composition of
      a uranium-reducing community comprised of Geobacter sulfurreducens, Rhodoferax
      ferrireducens, and Shewanella oneidensis. d-OptCom was also employed to examine
      the impact of lactate vs acetate addition on the relative abundance of uranium
      reducing species. These studies highlight the importance of simultaneously
      accounting for both species- and community-level fitness functions when modeling
      microbial communities, and demonstrate that the incorporation of uptake kinetic
      information can substantially improve the prediction of interspecies flux
      trafficking. Overall, this study paves the way for the dynamic multi-level and
      multi-objective analysis of microbial ecosystems.

PMID- 24742180
TI  - Implementation of hospital governing boards: views from the field.
AB  - BACKGROUND: Decentralization through the establishment of hospital governing
      boards has been touted as an effective way to improve the quality and efficiency
      of hospitals in low-income countries. Although several studies have examined the
      process of decentralization, few have quantitatively assessed the implementation
      of hospital governing boards and their impact on hospital performance. Therefore,
      we sought to describe the functioning of governing boards and to determine the
      association between governing board functioning and hospital performance.
      METHODS: We conducted a cross-sectional study with governing board chairpersons
      to assess board (1) structure, (2) roles and responsibilities and (3) training
      and orientation practices. Using bivariate analysis and multivariable regression,
      we examined the association between governing board functioning and hospital
      performance. Hospital performance indicators: 1) percent of hospital management
      standards met, measured with the Ethiopian Hospital Reform Implementation
      Guidelines and 2) patient experience, measured with the Inpatient and Outpatient
      Assessment of Healthcare surveys. RESULTS: A total of 92 boards responded to the
      survey (96% response rate). The average percentage of EHRIG standards met was
      58.1% (standard deviation (SD) 21.7 percentage points), and the mean overall
      patient experience score was 7.2 (SD 2.2). Hospitals with greater hospital
      management standards met had governing boards that paid members, reviewed
      performance in several domains quarterly or more frequently, developed new
      revenue sources, determined services to be outsourced, reviewed patient
      complaints, and had members with knowledge in business and financial management
      (all P-values < 0.05). Hospitals with more positive patient experience had
      governing boards that developed new revenue sources, determined services to be
      outsourced, and reviewed patient complaints (all P-values < 0.05). CONCLUSIONS:
      These cross-sectional data suggest that strengthening governing boards to perform
      essential responsibilities may result in improved hospital performance.

PMID- 24742181
TI  - Building on the EGIPPS performance assessment: the multipolar framework as a
      heuristic to tackle the complexity of performance of public service oriented
      health care organisations.
AB  - BACKGROUND: Performance of health care systems is a key concern of policy makers
      and health service managers all over the world. It is also a major challenge,
      given its multidimensional nature that easily leads to conceptual and
      methodological confusion. This is reflected by a scarcity of models that
      comprehensively analyse health system performance. DISCUSSION: In health, one of
      the most comprehensive performance frameworks was developed by the team of Leggat
      and Sicotte. Their framework integrates 4 key organisational functions (goal
      attainment, production, adaptation to the environment, and values and culture)
      and the tensions between these functions.We modified this framework to better fit
      the assessment of the performance of health organisations in the public service
      domain and propose an analytical strategy that takes it into the social
      complexity of health organisations. The resulting multipolar performance
      framework (MPF) is a meta-framework that facilitates the analysis of the
      relations and interactions between the multiple actors that influence the
      performance of health organisations. SUMMARY: Using the MPF in a dynamic
      reiterative mode not only helps managers to identify the bottlenecks that hamper
      performance, but also the unintended effects and feedback loops that emerge.
      Similarly, it helps policymakers and programme managers at central level to
      better anticipate the potential results and side effects of and required
      conditions for health policies and programmes and to steer their implementation
      accordingly.

PMID- 24742182
TI  - Acupuncture at local and distal points for chronic shoulder pain: study protocol
      for a randomized controlled trial.
AB  - BACKGROUND: Chronic shoulder pain (CSP) is the third most common type of
      musculoskeletal pain. It has a major impact on health-related quality of life. In
      Chinese medicine, CSP is considered one of the conditions most amenable to
      treatment with acupuncture. The purpose of this study is to evaluate the efficacy
      of local acupoints in combination with distal acupoints in pain relief and
      shoulder function improvement in CSP patients. METHODS/DESIGN: This is a
      multicenter, single blind, factorial randomized controlled clinical trial. A
      total of 164 participants will be randomly allocated to four different groups:
      Group A will receive acupuncture at local acupoints in combination with distal
      acupoint. Group B will receive acupuncture at local acupoints in combination with
      distal non-acupoint. Group C will receive acupuncture at local non-acupoints in
      combination with distal acupoint. Group D will receive acupuncture at local non
      acupoints in combination with distal non-acupoint. Each group will receive 12
      treatments of acupuncture one to three times per week for six weeks in total. The
      primary outcome is shoulder pain intensity, which is graded using a 100 -mm
      Visual Analogue Scale. The assessment is at baseline (before treatment
      initiation), 6 weeks after the first acupuncture, 10 weeks after the first
      acupuncture and 18 weeks after the first acupuncture. DISCUSSION: This trial will
      be helpful in identifying whether acupuncture at local acupoints in combination
      with distal acupoints may be more effective than needling points separately.
      TRIAL REGISTRATION: International Standard Randomized Controlled Trial Number
      Register: ISRCTN61861069 (http://www.controlled-trials.com).

PMID- 24742184
TI  - Interactive forces between lignin and cellulase as determined by atomic force
      microscopy.
AB  - BACKGROUND: Lignin is a complex polymer which inhibits the enzymatic conversion
      of cellulose to glucose in lignocellulose biomass for biofuel production.
      Cellulase enzymes irreversibly bind to lignin, deactivating the enzyme and
      lowering the overall activity of the hydrolyzing reaction solution. Within this
      study, atomic force microscopy (AFM) is used to compare the adhesion forces
      between cellulase and lignin with the forces between cellulase and cellulose, and
      to study the moiety groups involved in binding of cellulase to lignin. RESULTS:
      Trichoderma reesei, ATCC 26921, a commercial cellulase system, was immobilized
      onto silicon wafers and used as a substrate to measure forces involved in
      cellulase non-productive binding to lignin. Attraction forces between cellulase
      and lignin, and between cellulase and cellulose were compared using kraft lignin-
      and hydroxypropyl cellulose-coated tips with the immobilized cellulase substrate.
      The measured adhesion forces between kraft lignin and cellulase were on average
      45% higher than forces between hydroxypropyl cellulose and cellulase. Specialized
      AFM tips with hydrophobic, -OH, and -COOH chemical characteristics were used with
      immobilized cellulase to represent hydrophobic, H-bonding, and charge-charge
      interactions, respectively. Forces between hydrophobic tips and cellulase were on
      average 43% and 13% higher than forces between cellulase with tips exhibiting OH
      and COOH groups, respectively. A strong attractive force during the AFM tip
      approach to the immobilized cellulase was observed with the hydrophobic tip.
      CONCLUSIONS: This work shows that there is a greater overall attraction between
      kraft lignin and cellulase than between hydroxypropyl cellulose and cellulase,
      which may have implications during the enzymatic reaction process. Furthermore,
      hydrophobic interactions appear to be the dominating attraction force in
      cellulase binding to lignin, while a number of other interactions may establish
      the irreversible binding.

PMID- 24742183
TI  - Novel insights into transmission routes of Mycobacterium avium in pigs and
      possible implications for human health.
AB  - Mycobacterium avium infection is a severe condition in humans, whereas pigs are
      often subclinically infected. Pig carcasses represent a possible source of human
      infection. Faecal excretion of M. avium was recently demonstrated in
      experimentally infected pigs, along with detection of M. avium in apparently
      normal lymph nodes. The present study investigates faecal excretion in naturally
      infected herds and the presence of live mycobacteria in lymph nodes. Two pig
      herds (A and B), with a history of sporadically suspected M. avium infection were
      sampled. Herd B used peat, as opposed to Herd A. Samples from peat, sawdust,
      drinking water, faeces and lymph nodes were collected. Identification of
      mycobacteria was performed by 16S rDNA sequencing and PCR. Mycobacterium avium
      isolates were analysed by Multi-Locus Variable Number of Tandem repeat Analysis
      (MLVA). Mycobacterium avium subsp. hominissuis was detected in samples of faeces,
      peat and lymph nodes from Herd B, often with identical MLVA profiles.
      Additionally, other non-tuberculous mycobacteria (NTM) were found in the same
      material. The absence of macroscopic lymph node lesions in the presence of M.
      avium subsp. hominissuis was frequently demonstrated. In Herd A, only one NTM
      isolate, which proved not to be M. avium, was found. Faeces might facilitate
      transmission of M. avium subsp. hominissuis between pigs and maintain the
      infection pressure in herds. The low incidence of macroscopic lesions together
      with the massive presence of M. avium subsp. hominissuis in lymph nodes from pigs
      kept on peat raises questions related to animal husbandry, food safety and human
      health.

PMID- 24742185
TI  - Relationships between anthropometric measures and athletic performance, with
      special reference to repeated-sprint ability, in the Qatar national soccer team.
AB  - The aim of this study was to determine potential relationships between
      anthropometric parameters and athletic performance with special consideration to
      repeated-sprint ability (RSA). Sixteen players of the senior male Qatar national
      soccer team performed a series of anthropometric and physical tests including
      countermovement jumps without (CMJ) and with free arms (CMJwA), straight-line 20
      m sprint, RSA (6 * 35 m with 10 s recovery) and incremental field test.
      Significant (P < 0.05) relationships occurred between muscle-to-bone ratio and
      both CMJs height (r ranging from 0.56 to 0.69) as well as with all RSA-related
      variables (r < -0.53 for sprinting times and r = 0.54 for maximal sprinting
      speed) with the exception of the sprint decrement score (Sdec). The sum of six
      skinfolds and adipose mass index were largely correlated with Sdec (r = 0.68, P <
      0.01 and r = 0.55, P < 0.05, respectively) but not with total time (TT, r = 0.44
      and 0.33, P > 0.05, respectively) or any standard athletic tests. Multiple
      regression analyses indicated that muscular cross-sectional area for mid-thigh,
      adipose index, straight-line 20 m time, maximal sprinting speed and CMJwA are the
      strongest predictors of Sdec (r(2) = 0.89) and TT (r(2) = 0.95) during our RSA
      test. In the Qatar national soccer team, players' power-related qualities and RSA
      are associated with a high muscular profile and a low adiposity. This supports
      the relevance of explosive power for the soccer players and the larger importance
      of neuromuscular qualities determining the RSA.

PMID- 24742186
TI  - Solar-driven photoelectrochemical probing of nanodot/nanowire/cell interface.
AB  - We report a nitrogen-doped carbon nanodot (N-Cdot)/TiO2 nanowire photoanode for
      solar-driven, real-time, and sensitive photoelectrochemical probing of the
      cellular generation of H2S, an important endogenous gasotransmitter based on a
      tunable interfacial charge carrier transfer mechanism. Synthesized by a microwave
      assisted solvothermal method and subsequent surface chemical conjugation, the
      obtained N-Cdot/TiO2 nanowire photoanode shows much enhanced photoelectrochemical
      photocurrent compared with pristine TiO2 nanowires. This photocurrent increase is
      attributed to the injection of photogenerated electrons from N-Cdots to TiO2
      nanowires, confirmed by density functional theory simulation. In addition, the
      charge transfer efficiency is quenched by Cu(2+), whereas the introduction of H2S
      or S(2-) ions resets the charge transfer and subsequently the photocurrent, thus
      leading to sensitive photoelectrochemical recording of the H2S level in buffer
      and cellular environments. Moreover, this N-Cdot-TiO2 nanowire photoanode has
      been demonstrated for direct growth and interfacing of H9c2 cardiac myoblasts,
      with the capability of interrogating H2S cellular generation pathways by vascular
      endothelial growth factor stimulation as well as inhibition. 

PMID- 24742189
TI  - The decoupled mind: mind-wandering disrupts cortical phase-locking to perceptual
      events.
AB  - The mind flows in a "stream of consciousness," which often neglects immediate
      sensory input in favor of focusing on intrinsic, self-generated thoughts or
      images. Although considerable research has documented the disruptive influences
      of task-unrelated thought for perceptual processing and task performance, the
      brain dynamics associated with these phenomena are not well understood. Here we
      investigate the possibility, suggested by several convergent lines of research,
      that task-unrelated thought is associated with a reduction in the trial-to-trial
      phase consistency of the oscillatory neural signal in response to perceptual
      input. Using an experience sampling paradigm coupled with continuous high-density
      electroencephalography, we observed that task-unrelated thought was associated
      with a reduction of the P1 ERP, replicating prior observations that mind
      wandering is accompanied by a reduction of the brain-evoked response to sensory
      input. Time-frequency analysis of the oscillatory neural response revealed a
      decrease in theta-band cortical phase-locking, which peaked over parietal scalp
      regions. Furthermore, we observed that task-unrelated thought impacted the
      oscillatory mode of the brain during the initiation of a task-relevant action,
      such that more cortical processing was required to meet task demands. Together,
      these findings document that the attenuation of perceptual processing that occurs
      during task-unrelated thought is associated with a reduction in the temporal
      fidelity with which the brain responds to a stimulus and suggest that increased
      neural processing may be required to recouple attention to a task. More
      generally, these data provide novel confirmatory evidence for the mechanisms
      through which attentional states facilitate the neural processing of sensory
      input. 

PMID- 24742190
TI  - Transcranial direct current stimulation enhances verbal working memory training
      performance over time and near transfer outcomes.
AB  - Studies attempting to increase working memory (WM) capacity show promise in
      enhancing related cognitive functions but have also raised criticism in the
      broader scientific community given the inconsistent findings produced by these
      studies. Transcranial direct current stimulation (tDCS) has been shown to enhance
      WM performance in a single session [Fregni, F., Boggio, P., Nitsche, M.,
      Bermpohl, F., Anatal, A., Feredoes, E., et al. Anodal transcranial direct current
      stimulation of prefrontal cortex enhances working memory. Experimental Brain
      Research, 166, 23-30, 2005]; however, the extent to which tDCS might enhance
      learning on a WM training regime and the extent to which learning gains might
      transfer outside the training task remains largely unknown. To this end,
      participants engaged in an adaptive WM training task [previously utilized in
      Richmond, L., Morrison, A., Chein, J., & Olson, I. Working memory training and
      transfer in older adults. Psychology & Aging, 26, 813-822, 2011; Chein, J., &
      Morrison, A. Expanding the mind's workspace: Training and transfer effects with a
      complex working memory span task. Psychonomic Bulletin & Review, 17, 193-199,
      2010] for 10 sessions over 2 weeks, concurrent with either active or sham
      stimulation of dorsolateral pFC. Before and after training, a battery of tests
      tapping domains known to relate to WM abilities was administered. Results show
      that tDCS enhanced learning on the verbal portion of the training task by 3.65
      items. Furthermore, tDCS was shown to enhance near transfer to other untrained WM
      tasks in comparison with a no-contact control group. These results lend support
      to the idea that tDCS might bolster training and transfer gains in populations
      with compromised WM abilities. 

PMID- 24742191
TI  - Individual differences in the balance of GABA to glutamate in pFC predict the
      ability to select among competing options.
AB  - Individuals vary greatly in their ability to select one item or response when
      presented with a multitude of options. Here we investigate the neural
      underpinnings of these individual differences. Using magnetic resonance
      spectroscopy, we found that the balance of inhibitory versus excitatory
      neurotransmitters in pFC predicts the ability to select among task-relevant
      options in two language production tasks. The greater an individual's
      concentration of GABA relative to glutamate in the lateral pFC, the more quickly
      he or she could select a relevant word from among competing options. This outcome
      is consistent with our computational modeling of this task [Snyder, H. R.,
      Hutchison, N., Nyhus, E., Curran, T., Banich, M. T., O'Reilly, R. C., et al.
      Neural inhibition enables selection during language processing. Proceedings of
      the National Academy of Sciences, U.S.A., 107, 16483-16488, 2010], which predicts
      that greater net inhibition in pFC increases the efficiency of resolving
      competition among task-relevant options. Moreover, the association with the
      GABA/glutamate ratio was specific to selection and was not observed for executive
      function ability in general. These findings are the first to link the balance of
      excitatory and inhibitory neural transmission in pFC to specific aspects of
      executive function. 

PMID- 24742192
TI  - Day-to-day fluctuation of point-of-care circulating cathodic antigen test scores
      and faecal egg counts in children infected with Schistosoma mansoni in Ethiopia.
AB  - BACKGROUND: Determining the variation of circulating cathodic antigen (CCA) in
      urine and egg counts variation in stool between days in Schistosoma mansoni (S.
      mansoni) infected individuals is vital to decide whether or not to rely on a
      single-sample test for diagnosis of Schistosomiasis. In this study, the magnitude
      of day-to-day variation in urine-CCA test scores and in faecal egg counts was
      evaluated in school children in Ethiopia. METHODS: A total of 620 school children
      (age 8 to 12 years) were examined for S. mansoni infection using double Kato-Katz
      and single urine-CCA cassette methods (batch 32727) on three consecutive days.
      RESULTS: The prevalence of S. mansoni infection was 81.1% based on triple urine
      CCA-cassette test and 53.1% based on six Kato-Katz thick smears. Among the study
      participants, 26.3% showed fluctuation in urine CCA and 32.4% showed fluctuation
      in egg output. Mean egg count as well as number of cases in each class of
      intensity and intensity of cassette band color varied over the three days of
      examination. Over 85% of the children that showed day-to-day variations in status
      of S. mansoni infection from negative to positive or vice versa by the Kato-Katz
      and the CCA methods had light intensity of infection. The fluctuation in both the
      CCA test scores and faecal egg count was not associated with age and sex.
      CONCLUSIONS: The current study showed day-to-day variation in CCA and Kato-Katz
      test results of children infected with S. mansoni. This indicates the necessity
      of more than one urine or stool samples to be collected on different days for
      more reliable diagnosis of S. mansoni infection in low endemic areas.

PMID- 24742194
TI  - Evidence that diet-induced hyperleptinemia, but not hypothalamic gliosis, causes
      ghrelin resistance in NPY/AgRP neurons of male mice.
AB  - High-fat diet (HFD) feeding causes ghrelin resistance in arcuate neuropeptide Y
      (NPY)/Agouti-related peptide neurons. In the current study, we investigated the
      time course over which this occurs and the mechanisms responsible for ghrelin
      resistance. After 3 weeks of HFD feeding, neither peripheral nor central ghrelin
      increased food intake and or activated NPY neurons as demonstrated by a lack of
      Fos immunoreactivity or whole-cell patch-clamp electrophysiology. Pair-feeding
      studies that matched HFD calorie intake with chow calorie intake show that HFD
      exposure does not cause ghrelin resistance independent of body weight gain. We
      observed increased plasma leptin in mice fed a HFD for 3 weeks and show that
      leptin-deficient obese ob/ob mice are still ghrelin sensitive but become ghrelin
      resistant when central leptin is coadministered. Moreover, ob/ob mice fed a HFD
      for 3 weeks remain ghrelin sensitive, and the ability of ghrelin to induce action
      potential firing in NPY neurons was blocked by leptin. We also examined
      hypothalamic gliosis in mice fed a chow diet or HFD, as well as in ob/ob mice fed
      a chow diet or HFD and lean controls. HFD-fed mice exhibited increased glial
      fibrillary acidic protein-positive cells compared with chow-fed mice, suggesting
      that hypothalamic gliosis may underlie ghrelin resistance. However, we also
      observed an increase in hypothalamic gliosis in ob/ob mice fed a HFD compared
      with chow-fed ob/ob and lean control mice. Because ob/ob mice fed a HFD remain
      ghrelin sensitive, our results suggest that hypothalamic gliosis does not
      underlie ghrelin resistance. Further, pair-feeding a HFD to match the calorie
      intake of chow-fed controls did not increase body weight gain or cause central
      ghrelin resistance; thus, our evidence suggests that diet-induced
      hyperleptinemia, rather than diet-induced hypothalamic gliosis or HFD exposure,
      causes ghrelin resistance. 

PMID- 24742193
TI  - Antiandrogen flutamide protects male mice from androgen-dependent toxicity in
      three models of spinal bulbar muscular atrophy.
AB  - Spinal and bulbar muscular atrophy (SBMA) is a late-onset, progressive
      neurodegenerative disease linked to a polyglutamine (polyQ) expansion in the
      androgen receptor (AR). Men affected by SBMA show marked muscle weakness and
      atrophy, typically emerging midlife. Given the androgen-dependent nature of this
      disease, one might expect AR antagonists to have therapeutic value for treating
      SBMA. However, current work from animal models suggests otherwise, raising
      questions about whether polyQ-expanded AR exerts androgen-dependent toxicity
      through mechanisms distinct from normal AR function. In this study, we asked
      whether the nonsteroidal AR antagonist flutamide, delivered via a time-release
      pellet, could reverse or prevent androgen-dependent AR toxicity in three
      different mouse models of SBMA: the AR97Q transgenic (Tg) model, a knock-in (KI)
      model, and a myogenic Tg model. We find that flutamide protects mice from
      androgen-dependent AR toxicity in all three SBMA models, preventing or reversing
      motor dysfunction in the Tg models and significantly extending the life span in
      KI males. Given that flutamide effectively protects against androgen-dependent
      disease in three different mouse models of SBMA, our data are proof of principle
      that AR antagonists have therapeutic potential for treating SBMA in humans and
      support the notion that toxicity caused by polyQ-expanded AR uses at least some
      of the same mechanisms as normal AR before diverging to produce disease and
      muscle atrophy. 

PMID- 24742195
TI  - Expression and regulation of neuromedin B in pituitary corticotrophs of male
      melanocortin 2 receptor-deficient mice.
AB  - The hypothalamic-pituitary-adrenal (HPA) axis is a major part of the
      neuroendocrine system that controls responses to stress, and has an important
      function in the regulation of various body processes. We previously created a
      mouse line deficient in the melanocortin 2 receptor (MC2R). MC2R-deficient mice
      (MC2R(-/-) mice) have high adrenocorticotropic hormone (ACTH) levels because of
      undetectable corticosterone levels. Increased neuromedin B (NMB) expression was
      recently reported in the pituitary gland of adrenalectomized mice, a model for
      acute adrenal insufficiency. To investigate gene expression in the pituitary
      gland under chronic adrenal deficiency, we examined the pituitary gland of MC2R(
      /-) mice, a model of chronic adrenal insufficiency. To understand the molecular
      background of pituitary cells under chronic adrenal deficiency, we first
      performed DNA microarray analyses using the pituitary glands of the MC2R(-/-)
      mice. The DNA microarray analysis and real-time polymerase chain reaction showed
      that NMB expression was higher in the MC2R(-/-) than in the wild-type (WT) mice.
      We detected NMB expression in the MC2R(-/-) pituitary corticotrophs by
      immunohistochemistry using the specific antibodies for ACTH and NMB. In addition,
      the plasma NMB concentration was significantly higher in the MC2R(-/-) mice than
      in the WT mice. Subcutaneous implantation of a sustained-release corticosterone
      pellet decreased the expression of NMB mRNA as well as pituitary
      proopiomelanocortin mRNA. In isolated anterior pituitary cells, NMB mRNA
      expression was increased by the administration of corticotropin-releasing hormone
      (CRH) and was suppressed by dexamethasone treatment. In this study, we first
      demonstrate NMB expression in corticotrophs and its regulation by CRH and
      glucocorticoids. Furthermore, corticotrophs seemed to secrete NMB into the
      systemic circulation. 

PMID- 24742197
TI  - Associations between renal impairment and anemia in older, rural Japanese men:
      the Nagasaki Island study.
AB  - BACKGROUND: Renal impairment is known to be associated with atherosclerosis,
      which in turn is reported to be positively associated with hemoglobin levels. In
      addition, renal impairment is known to be associated with a form of anemia known
      as renal anemia. METHODS: To clarify the associations between renal impairment
      and anemia, we conducted a cross-sectional study of 1,105 60 to 89-year-old men,
      who were not taking medication for anemia and were undergoing general health
      check-ups. RESULTS: Compared with non-chronic kidney disease, chronic kidney
      disease (CKD) with a glomerular filtration rate (GFR) <60 mL/min/1.73 m2 was
      found to constitute a significant risk of anemia. However, we noted that this
      risk was lower for mild renal impairment (60 mL/min/1.73 m2 <= GFR <90
      mL/min/1.73 m2). Compared with the non-CKD reference group, the classical
      cardiovascular risk factors adjusted odds ratio (OR) for anemia was 1.81 (1.23 to
      2.68) and compared with the normal renal function (GFR >=90 mL/min/1.73 m2)
      reference group, the ORs for mild renal impairment and CKD were 0.26 (0.15 to
      0.47) and 0.60 (0.33 to 1.09). CONCLUSIONS: Independent from classical
      cardiovascular risk factors, CKD, which was identified during general health
      check-ups, appeared to constitute a significant risk of anemia for older Japanese
      men. For mild renal impairment, however, this association was a reduced risk of
      anemia and thus possibly a higher risk of atherosclerosis.

PMID- 24742196
TI  - Nonmyocytic androgen receptor regulates the sexually dimorphic development of the
      embryonic bulbocavernosus muscle.
AB  - The bulbocavernosus (BC) is a sexually dimorphic muscle observed only in males.
      Androgen receptor knockout mouse studies show the loss of BC formation. This
      suggests that androgen signaling plays a vital role in its development. Androgen
      has been known to induce muscle hypertrophy through satellite cell activation and
      myonuclei accretion during muscle regeneration and growth. Whether the same
      mechanism is present during embryonic development is not yet elucidated. To
      identify the mechanism of sexual dimorphism during BC development, the timing of
      morphological differences was first established. It was revealed that the BC was
      morphologically different between male and female mice at embryonic day (E) 16.5.
      Differences in the myogenic process were detected at E15.5. The male BC possesses
      a higher number of proliferating undifferentiated myoblasts. To identify the role
      of androgen signaling in this process, muscle-specific androgen receptor (AR)
      mutation was introduced, which resulted in no observable phenotypes. Hence, the
      expression of AR in the BC was examined and found that the AR did not colocalize
      with any muscle markers such as Myogenic differentiation 1, Myogenin, and paired
      box transcription factor 7. It was revealed that the mesenchyme surrounding the
      BC expressed AR and the BC started to express AR at E15.5. AR mutation on the
      nonmyocytic cells using spalt-like transcription factor 1 (Sall1) Cre driver
      mouse was performed, which resulted in defective BC formation. It was revealed
      that the number of proliferating undifferentiated myoblasts was reduced in the
      Sall1 Cre:AR(L-/Y) mutant embryos, and the adult mutants were devoid of BC. The
      transition of myoblasts from proliferation to differentiation is mediated by
      cyclin-dependent kinase inhibitors. An increased expression of p21 was observed
      in the BC myoblast of the Sall1 Cre:AR(L-/Y) mutant and wild-type female.
      Altogether this study suggests that the nonmyocytic AR may paracrinely regulate
      the proliferation of myoblast possibly through inhibiting p21 expression in
      myoblasts of the BC. 

PMID- 24742199
TI  - Baseline performance and learning rate of conceptual and perceptual skill
      learning tasks: the effect of moderate to severe traumatic brain injury.
AB  - Existing literature presents a complex and inconsistent picture of the specific
      deficiencies involved in skill learning following traumatic brain injury (TBI).
      In an attempt to address this difficulty, individuals with moderate to severe TBI
      (n = 29) and a control group (n = 29) were tested with two different skill
      learning tasks: conceptual (i.e., Tower of Hanoi Puzzle, TOHP) and perceptual
      (i.e., mirror reading, MR). Based on previous studies of the effect of divided
      attention on these tasks and findings regarding the effect of TBI on conceptual
      and perceptual priming tasks, it was predicted that the group with TBI would show
      impaired baseline performance compared to controls in the TOHP task though their
      learning rate would be maintained, while both baseline performance and learning
      rate on the MR task would be maintained. Consistent with our predictions, overall
      baseline performance of the group with TBI was impaired in the TOHP test, while
      the learning rate was not. The learning rate on the MR task was preserved but,
      contrary to our prediction, response time of the group with TBI was slower than
      that of controls. The pattern of results observed in the present study was
      interpreted to possibly reflect an impairment of both the frontal lobes as well
      as that of diffuse axonal injury, which is well documented as being affected by
      TBI. The former impairment affects baseline performance of the conceptual
      learning skill, while the latter affects the overall slower performance of the
      perceptual learning skill. 

PMID- 24742198
TI  - Levels and values of lipoprotein-associated phospholipase A2, galectin-3,
      RhoA/ROCK, and endothelial progenitor cells in critical limb ischemia: pharmaco
      therapeutic role of cilostazol and clopidogrel combination therapy.
AB  - OBJECTIVE: We tested the hypothesis that clopidogrel and cilostazol combination
      therapy could effectively attenuate systemic inflammatory reaction, facilitate
      proliferation of circulating endothelial progenitor cell (EPC), and improve the
      clinical outcomes of critical limb ischemia (CLI) in patients unsuitable for
      surgical revascularization or percutaneous transluminal angioplasty (PTA).
      METHODS: A total 55 patients (mean age, 72 years; 56% female) were consecutively
      enrolled. Clopidogrel and cilostazol combination therapy was administered
      throughout the study period. RESULTS: As compared with the baseline, circulating
      endothelial progenitor cell level (as shown by flow cytometry) was significantly
      increased (p<0.003), whereas the CLI-related ulcers and painfulness were
      significantly improved (all p<0.01) by day 90 after treatment. On the other hand,
      after clopidogrel and cilostazol combination therapy, galectin-3 level,
      lipoprotein-associated phospholipase A2 gene expression, and RhoA/ROCK-related
      protein expression in peripheral blood mononuclear cells were significantly
      suppressed (all p<0.01). Eventually, by day 90, 5 patients (9.1%) died of other
      etiologies, 3 (5.5%) withdrew from the study, 6 (10.9%) required amputation, and
      the remaining 41 had satisfactory clinical improvement with complete wound
      healing in 9 (16.4%) patients. CONCLUSION: The results of the present study
      highlight that clopidogrel and cilostazol combination therapy may be considered
      to be an alternative method for treating patients with CLI unsuitable for
      surgical revascularization or PTA.

PMID- 24742200
TI  - Novel endosomolytic poly(amido amine) polymer conjugates for systemic delivery of
      siRNA to hepatocytes in rodents and nonhuman primates.
AB  - The application of small interfering (si)RNAs as potential therapeutic agents
      requires safe and effective methods for their delivery to the cytoplasm of the
      target cells and tissues. Recent studies have shown significant progress in the
      development of targeting reagents that facilitate the recognition of, and siRNA
      delivery to, specific cell types. Among recently reported delivery approaches,
      polymers with amphipathic properties have been used to enable endosome escape and
      cytosolic delivery. Here, we describe a linear amphipathic poly(amido amine)
      polymer conjugate system for the efficient siRNA delivery in vitro and in vivo.
      This polymer contains a novel amine bearing bis-acrylamide monomer designed for
      increasing amine density, which resulted in substantial improvement in liver
      uptake and RNAi activity compared to our previously reported poly(amido amine
      disulfide) polymer.1 The activity for this liver targeted delivery system was
      demonstrated in rodents and nonhuman primates.

PMID- 24742201
TI  - Degradation of methicillin-resistant Staphylococcus aureus biofilms using a
      chimeric lysin.
AB  - Methicillin-resistant Staphylococcus aureus (MRSA) is responsible for a large
      number of chronic infections due to its ability to form robust biofilms. Herein,
      the authors evaluated the anti-biofilm activity of a Staphylococcus specific
      chimeric lysin ClyH on MRSA biofilms. ClyH is known to be active against
      planktonic MRSA cells in vitro and in vivo. The minimum concentrations for
      biofilm eradication (MCBE) of ClyH were 6.2-50 mg l(-1), much lower than those of
      antibiotics. Scanning electron microscope (SEM) analysis revealed that ClyH
      eliminated MRSA biofilms through cell lytic activity in a time-dependent manner.
      Viable plate counts and kinetic analysis demonstrated that biofilms of different
      ages displayed varying susceptibility to ClyH. Together with previously
      demonstrated in vivo efficacy of ClyH against MRSA, the degradation efficacy
      against biofilms of different ages indicates that ClyH could be used to remove
      MRSA biofilms in vivo. 

PMID- 24742202
TI  - Unprotected sex among men who have sex with men living with HIV in Brazil: a
      cross-sectional study in Rio de Janeiro.
AB  - BACKGROUND: Many countries are facing concentrated HIV epidemics among vulnerable
      populations, including men who have sex with men (MSM). Unprotected anal
      intercourse (UAI) is the main HIV transmission route among them and its
      understanding in the different cultures and how it relates to HIV transmission,
      re-infection and development of HIV antiretroviral resistance has important
      public health implications. Data on UAI among Brazilian MSM are scarce. This
      study aims to evaluate the prevalence and associated factors of UAI among HIV
      infected MSM who had sex with seronegative or male partners with an unknown
      serostatus. METHOD: A cross-sectional study nested in a cohort was conducted in
      Rio de Janeiro, Brazil. The one hundred and fifty five MSM included in the study
      answered an ACASI interview and provided biological samples. Generalized linear
      models were used to identify variables associated with UAI. RESULTS: Overall, UAI
      with an HIV-negative or unknown serostatus male partner was reported by 40.6%
      (63/155) of MSM. Lifetime sexual abuse or domestic violence was reported by
      35.9%, being more frequent among MSM who reported UAI compared to those who did
      not (P = 0.001). Use of stimulants before sex was reported by 20% of the MSM,
      being slightly higher among those who reported UAI (27.0% vs. 15.2%; P = 0.072).
      Commercial sex was frequent among all MSM (48.4%). After multivariate modeling,
      the report of sexual abuse or domestic violence (OR = 2.70; 95% CI: 1.08-7.01),
      commercial sex (OR = 2.28; 95% CI: 1.04- 5.10), the number of male sexual
      partners (p = 0.039) and exclusively receptive anal intercourse (OR = 0.21; 95%
      CI: 0.06-0.75) remained associated with UAI. CD4 levels, HIV viral load and
      antiretroviral therapy were not associated with UAI. CONCLUSION: The UAI
      prevalence found with negative or unknown HIV status partners points out that
      other interventions are needed as additional prevention tools to vulnerable MSM.
      The main factors associated with UAI were a lifetime history of violence,
      commercial sex and the number of male sexual partners. This clustering of
      different behavioral, health and social problems in this population reinforce the
      need of a comprehensive approach on treating and preventing HIV among MSM.

PMID- 24742203
TI  - Second generation steroidal 4-aminoquinolines are potent, dual-target inhibitors
      of the botulinum neurotoxin serotype A metalloprotease and P. falciparum malaria.
AB  - Significantly more potent second generation 4-amino-7-chloroquinoline (4,7-ACQ)
      based inhibitors of the botulinum neurotoxin serotype A (BoNT/A) light chain were
      synthesized. Introducing an amino group at the C(3) position of the cholate
      component markedly increased potency (IC50 values for such derivatives ranged
      from 0.81 to 2.27 MUM). Two additional subclasses were prepared: bis(steroidal)
      4,7-ACQ derivatives and bis(4,7-ACQ)cholate derivatives; both classes provided
      inhibitors with nanomolar-range potencies (e.g., the Ki of compound 67 is 0.10
      MUM). During BoNT/A challenge using primary neurons, select derivatives protected
      SNAP-25 by up to 89%. Docking simulations were performed to rationalize the
      compounds' in vitro potencies. In addition to specific residue contacts,
      coordination of the enzyme's catalytic zinc and expulsion of the enzyme's
      catalytic water were a consistent theme. With respect to antimalarial activity,
      the compounds provided better IC90 activities against chloroquine resistant (CQR)
      malaria than CQ, and seven compounds were more active than mefloquine against CQR
      strain W2. 

PMID- 24742204
TI  - Stakeholders' perception on the organization of chronic care: a SWOT analysis to
      draft avenues for health care reforms.
AB  - BACKGROUND: Adequate care for individuals living with chronic illnesses calls for
      a healthcare system redesign, moving from acute, disease-centered to patient
      centered models. The aim of this study was to identify Belgian stakeholders'
      perceptions on the strengths, weaknesses, opportunities and threats of the
      healthcare system for people with chronic diseases in Belgium. METHODS: Four
      focus groups were held with stakeholders from the micro and meso level, in
      addition to two interviews with stakeholders who could not attend the focus group
      sessions. Data collection and the discussion were based on the Chronic Care
      model. Thematic analysis of the transcripts allowed for the identification of the
      strengths, weaknesses, opportunities and threats of the current health care
      system with focus on chronic care. RESULTS: Informants stressed the overall good
      quality of the acute health care system and the level of reimbursement of care as
      an important strength of the current system. In contrast, the lack of integration
      of care was identified as one of the biggest weaknesses of today's health care
      system, along with the unclear definitions of the roles and functions of health
      professionals involved in care processes. Patient education to support self
      management exists for patients with diabetes and/or terminal kidney failure but
      not for those living with other or multiple chronic conditions. The current
      overall fee-for-service system is a barrier to integrated care, as are the lack
      of incentives for integrated care. Attending multidisciplinary meetings, for
      example, is underfinanced to date. Finally, clinical information systems lack
      interoperability, which further impedes the information flow across settings and
      disciplines. CONCLUSION: Our study's methods allowed for the identification of
      problematic domains in the health system for people living with chronic
      conditions. These findings provided useful insights surrounding perceived
      priorities. This methodology may inspire other countries faced with the challenge
      of drafting reforms to tackle the issue of chronic care.

PMID- 24742205
TI  - Neural correlates of moral judgments in first- and third-person perspectives:
      implications for neuroethics and beyond.
AB  - BACKGROUND: There appears to be an inconsistency in experimental paradigms used
      in fMRI research on moral judgments. As stimuli, moral dilemmas or moral
      statements/ pictures that induce emotional reactions are usually employed; a main
      difference between these stimuli is the perspective of the participants
      reflecting first-person (moral dilemmas) or third-person perspective (moral
      reactions). The present study employed functional magnetic resonance imaging
      (fMRI) in order to investigate the neural correlates of moral judgments in either
      first- or third-person perspective. RESULTS: Our results indicate that different
      neural mechanisms appear to be involved in these perspectives. Although
      conjunction analysis revealed common activation in the anterior medial prefrontal
      cortex, third person-perspective elicited unique activations in hippocampus and
      visual cortex. The common activation can be explained by the role the anterior
      medial prefrontal cortex may play in integrating different information types and
      also by its involvement in theory of mind. Our results also indicate that the so
      called "actor-observer bias" affects moral evaluation in the third-person
      perspective, possibly due to the involvement of the hippocampus. We suggest two
      possible ways in which the hippocampus may support the process of moral judgment:
      by the engagement of episodic memory and its role in understanding the behaviors
      and emotions of others. CONCLUSION: We posit that these findings demonstrate that
      first or third person perspectives in moral cognition involve distinct neural
      processes, that are important to different aspects of moral judgments. These
      results are important to a deepened understanding of neural correlates of moral
      cognition-the so-called "first tradition" of neuroethics, with the caveat that
      any results must be interpreted and employed with prudence, so as to heed
      neuroethics "second tradition" that sustains the pragmatic evaluation of
      outcomes, capabilities and limitations of neuroscientific techniques and
      technologies.

PMID- 24742206
TI  - Acute kidney injury influences mortality in lung transplantation.
AB  - OBJECTIVE: To evaluate the association between acute kidney injury (AKI) and long
      term survival in lung transplant patients. METHODS: Clinical data of 88 patients
      who underwent lung transplantation (LTx) were retrospectively analyzed at our
      institution from September 2002 to December 2011. Postoperative AKI was defined
      and divided into three groups based on creatinine criteria from the Acute Kidney
      Injury Net (AKIN) classification. A multivariable logistic regression model
      evaluated risk factors for AKI. Primary outcome was 5-year mortality. Risk
      adjusted multivariable COX proportional hazards regression examined the
      association of AKI with mortality. RESULTS: A total of 47 (53.40%) patients
      developed AKI (27 with AKIN1, 20 with AKIN2-3) in the first week after LTx.
      Multivariate analysis showed pre-LT (pre-lung transplant) hypertension (OR 1.37
      [0.06-2.68], p=0.041) and mechanical ventilation (OR 0.05 [0.01-0.09], p=0.022)
      were risk factors for postoperative AKI. Five-year survival rates in the non-AKI,
      AKIN1, and AKIN2-3 groups were 48.8%, 37.0%, 30.0%, respectively (p=0.041).
      Adjusted for age, sex, type and cause of LT, hypertension and diabetes, the
      hazard ratio for death was 1.481 ([1.040-2.107]) for AKI. CONCLUSIONS: The
      occurrence of AKI after LTx is common. Severe AKI would increase long-term
      mortality risk. Several variables, including pre-LT hypertension and mechanical
      ventilation, are associated with AKI after LTx.

PMID- 24742207
TI  - Renalase might be associated with hypertension and insulin resistance in Type 2
      diabetes.
AB  - BACKGROUND AND OBJECTIVES: Renalase, a monoamine oxidase derived from the kidney,
      can degrade catecholamine (CA) and regulate blood pressure as well as cardiac
      function. To investigate the changes of serum renalase levels in patients with
      Type 2 diabetes mellitus (DM) and examine the correlation with other features of
      T2DM. METHODS: Seventy-five patients with T2DM and 13 healthy volunteers were
      studied. The levels of serum renalase and CA were measured by enzyme linked
      immunosorbent assay. Several other biochemical and clinical parameters were
      measured. RESULTS: Serum levels of CA and renalase as well as renalase/CA (R/C)
      ratio in the T2DM group were significantly higher than those of the control group
      (p<0.05). There was a highly positive correlation between the levels of serum
      renalase and CA (r=0.795, p<0.001). The levels of serum renalase were positively
      correlated with systolic blood pressure (r=0.217, p=0.042) and serum creatinine
      (SCr) (r=0.295, p=0.007), and negatively correlated with eGFR (r=-0.222,
      p=0.044). The R/C ratio was positively correlated with SCr (r=0.347, p=0.001) as
      well as homeostasis model assessment for insulin resistance (IR) HOMA2-% S
      (r=0.340, p=0.037). CONCLUSION: Serum levels of renalase and CA were highly
      correlated in patients with T2DM. The levels of serum renalase and R/C ratio of
      T2DM patients were significantly higher than those of healthy subjects and
      appeared correlated with changes in blood pressure, glomerular filtration rate
      and IR.

PMID- 24742208
TI  - Mesenteric lymph duct ligation after hemorrhagic shock enhances the ATP level and
      ATPase activity in rat kidneys.
AB  - BACKGROUND: Kidney injury commonly occurs following hemorrhagic shock. This study
      aims to observe the effects of mesenteric lymph duct ligation (MLDL) on the
      adenosine triphosphate (ATP) levels and the cell membrane adenosine
      triphosphatase (ATPase) activity in the kidneys of rats subjected to hemorrhagic
      shock. METHODS: Wistar rats were assigned into sham, shock, and ligation groups.
      The hemorrhagic shock model was established in the shock and ligation groups, and
      MLDL was performed in the ligation group after resuscitation. Renal homogenates
      were prepared to determine the ATP and ATPase levels at 90 min after hemorrhage
      and at 0, 1, 3, 6, 12, and 24 h after resuscitation. RESULTS: The ATP levels, and
      the Na(+)-K(+)-ATPase, Mg(2+)-ATPase, Ca(2+)-ATPase, and Ca(2+)-Mg(2+)-ATPase
      activities in the renal tissue of the shock group were lower than those in the
      sham group at the multiple time points. Furthermore, the corresponding values in
      the ligation group were significantly higher than those in the shock group at
      multiple time points. CONCLUSION: MLDL improves energy metabolism and enhances
      the ATPase activity in the kidneys of hemorrhagic shock rats, along with other
      mechanisms that alleviate renal injury after hemorrhagic shock.

PMID- 24742209
TI  - Npro of classical swine fever virus contributes to pathogenicity in pigs by
      preventing type I interferon induction at local replication sites.
AB  - Classical swine fever (CSF) caused by CSF virus (CSFV) is a highly contagious
      disease of pigs. The viral protein Npro of CSFV interferes with alpha- and beta
      interferon (IFN-alpha/beta) induction by promoting the degradation of interferon
      regulatory factor 3 (IRF3). During the establishment of the live attenuated CSF
      vaccine strain GPE-, Npro acquired a mutation that abolished its capacity to bind
      and degrade IRF3, rendering it unable to prevent IFN-alpha/beta induction. In a
      previous study, we showed that the GPE- vaccine virus became pathogenic after
      forced serial passages in pigs, which was attributed to the amino acid
      substitutions T830A in the viral proteins E2 and V2475A and A2563V in NS4B.
      Interestingly, during the re-adaptation of the GPE- vaccine virus in pigs, the
      IRF3-degrading function of Npro was not recovered. Therefore, we examined whether
      restoring the ability of Npro to block IFN-alpha/beta induction of both the
      avirulent and moderately virulent GPE--derived virus would enhance pathogenicity
      in pigs. Viruses carrying the N136D substitution in Npro regained the ability to
      degrade IRF3 and suppress IFN-alpha/beta induction in vitro. In pigs, functional
      Npro significantly reduced the local IFN-alpha mRNA expression in lymphoid organs
      while it increased quantities of IFN-alpha/beta in the circulation, and enhanced
      pathogenicity of the moderately virulent virus. In conclusion, the present study
      demonstrates that functional Npro influences the innate immune response at local
      sites of virus replication in pigs and contributes to pathogenicity of CSFV in
      synergy with viral replication.

PMID- 24742210
TI  - Antifungal and antioxidant activity of Crassocephalum bauchiense (Hutch.) Milne
      Redh ethyl acetate extract and fractions (Asteraceae).
AB  - BACKGROUND: Crassocephalum bauchiense is a flowering plant, found in the West
      Region of Cameroon. Previous studied has highlighted the antibacterial and the
      dermal toxicological safety as well as the immunomodulatory activities of the
      ethyl acetate extract of its dry leaves. As an extension of the previous
      researches, the current work has been undertaken to evaluate the in vitro
      antifungal and antioxidant activities of C. bauchiense dried leaves ethyl acetate
      extract and fractions. METHODS: The extract was obtained by maceration in ethyl
      acetate and further fractionated into six fractions labeled F1 to F6 by flash
      chromatography. The antifungal activity of the extract and fractions against
      yeasts and dermatophytes was evaluated using broth microdilution method.
      Antioxidant activity was evaluated using 2,2-diphenyl-1-picrylhydrazyl (DPPH),
      nitric oxide (NO) and beta-carotene - linoleic acid assays. RESULTS: The extract
      (MIC = 0.125 - 4 mg/ml) was found to be more active on dermatophytes and yeasts
      compared to the fractions. The ethyl acetate extract and fractions exhibited
      strong scavenging activity on DPPH (CI50 = 28.57 - 389.38 MUg/ml). The fractions
      F3 and F6 expressed best antioxidant activity on DPPH radicals compared to the
      crude extract. CONCLUSION: The results of these findings clearly showed that C.
      bauchiense ethyl acetate extract has a significant antifungal and antioxidant
      activity. It is therefore a source of active compounds that might be used as
      antifungal and antioxidant agents.

PMID- 24742211
TI  - A novel model to predict the risk of readmission in patients with renal colic.
AB  - Abstract Purpose: To identify the clinical, laboratory, and imaging parameters
      that may increase the risk of readmission in patients with renal colic that is
      managed by active surveillance and to produce a novel model to predict the risk
      for this. PATIENTS AND METHODS: We retrospectively reviewed patients with renal
      colic secondary to ureteral calculi admitted to our hospital from March 2009
      until September 2010. The colic was managed with active surveillance for 6 weeks.
      Patients were divided into those who were not readmitted to the hospital within
      the follow-up period (group A) and those who were (group B). RESULTS: From the
      452 studied patients, 82 (18.1%) were readmitted to the hospital. Stone size
      (P<0.001) and location (P<0.001) and serum white blood cell count (P=0.009) were
      statistically significantly different between groups. These parameters were found
      to be independent predictors for readmission. A predictive model was produced to
      calculate the risk of readmission. CONCLUSIONS: Stone size and location and white
      blood cell count are independent predictors for potential readmission in patients
      with renal colic. Using these parameters, we may calculate the risk for
      readmission, and the latter may assist physicians in identifying the best
      treatment option.

PMID- 24742212
TI  - Physicians' propensity to discuss prognosis is associated with patients'
      awareness of prognosis for metastatic cancers.
AB  - BACKGROUND: Prognosis discussion is an essential component of informed decision
      making. However, many terminally ill patients have a limited awareness of their
      prognosis and the causes are unclear. OBJECTIVE: To explore the impact of
      physicians' propensity to discuss prognosis on advanced cancer patients'
      prognosis awareness. DESIGN: Cancer Care Outcomes Research and Surveillance
      Consortium (CanCORS) study, a prospective cohort study with patient and physician
      surveys. SETTING/SUBJECTS: We investigated 686 patients with metastatic lung or
      colorectal cancer at diagnosis who participated in the CanCORS study and reported
      about their life expectancy. Data were linked to the physician survey from 486
      physicians who were identified by these patients as filling important roles in
      their cancer care. RESULTS: Few patients with metastatic cancers (16.5%) reported
      an accurate awareness of their prognosis, defined as reporting a life expectancy
      of less than 2 years for lung cancer or less than 5 years for colorectal cancer.
      Patients whose most-important-doctor (in helping patient make decisions) reported
      discussing prognosis with terminally ill patients earlier were more likely than
      those whose doctors deferred these discussions to have an accurate prognosis
      awareness (adjusted proportion, 18.5% versus 7.6%; odds ratio, 3.23; 95%
      confidence interval, 1.39-7.52; p=0.006). CONCLUSIONS: Few patients with advanced
      cancer could articulate an accurate prognosis estimate, despite most having
      received chemotherapy and many physicians reported they would discuss prognosis
      early. Physicians' propensity to discuss prognosis earlier was associated with
      more accurate patient reports of prognosis. Enhancing the communication skills of
      providers with important roles in cancer care may help to improve cancer
      patients' understanding of their prognosis.

PMID- 24742218
TI  - Time-resolved coherent diffraction of ultrafast structural dynamics in a single
      nanowire.
AB  - The continuing effort to utilize the unique properties present in a number of
      strongly correlated transition metal oxides for novel device applications has led
      to intense study of their transitional phase state behavior. Here we report on
      time-resolved coherent X-ray diffraction measurements on a single vanadium
      dioxide nanocrystal undergoing a solid-solid phase transition, using the SACLA X
      ray Free Electron Laser (XFEL) facility. We observe an ultrafast transition from
      monoclinic to tetragonal crystal structure in a single vanadium dioxide
      nanocrystal. Our findings demonstrate that the structural change occurs in a
      number of distinct stages attributed to differing expansion modes of vanadium
      atom pairs. 

PMID- 24742217
TI  - The process of developing and implementing a telephone-based peer support program
      for postpartum depression: evidence from two randomized controlled trials.
AB  - BACKGROUND: A randomized controlled trial evaluated the effect of telephone-based
      peer support on preventing postpartum depression (PPD) among high-risk mothers.
      The results indicated that support provided by peer volunteers may be an
      effective preventative strategy. The purpose of this paper is to outline the
      process of developing, implementing, maintaining, and evaluating the peer support
      program that we used in this PPD prevention trial. METHODS: The peer support
      program had been used successfully in a pilot trial and a previous breastfeeding
      peer support trial. Based on our experience and lessons learned, we developed a 4
      phase, 12-step approach so that the peer support model could be copied and used
      by different health providers in various settings. We will use the PPD prevention
      trial to demonstrate the suggested steps. RESULTS: The trial aim to prevent the
      onset of PPD was established. Peer volunteers who previously experienced and
      recovered from self-reported PPD were recruited and attended a four-hour training
      session. Volunteers were screened and those identified as appropriate to provide
      support to postpartum mothers were selected. Women who scored more than 9 on the
      Edinburgh Postnatal Depression Scale within the first two weeks after childbirth
      were recruited to participate in the trial and proactive, individualized,
      telephone-based peer support (mother-to-mother) was provided to those randomized
      to the intervention group. Peer volunteers maintained the intervention, supported
      other volunteers, and evaluated the telephone-based support program. Possible
      negative effects of the intervention were assessed. An in-depth assessment of
      maternal perspectives of the program at 12 weeks postpartum was performed.
      CONCLUSIONS: The 4-phase, 12-step approach delineated in this paper provides
      clear and concise guidelines for health professionals to follow in creating and
      implementing community-based, peer-support interventions with the potential to
      prevent PPD. TRIAL REGISTRATION: Current Controlled Trials ISRCTN68337727.

PMID- 24742220
TI  - Prevalence of BRCA1 and BRCA2 mutations in unselected breast cancer patients from
      medellin, Colombia.
AB  - BACKGROUND: Approximately 5% of all breast cancers can be attributed to a
      mutation in the BRCA1 or BRCA2 gene. The genetic component of breast cancer in
      Colombia has been, for the most part, studied on cases from the Bogota region.
      Five different founder mutations were in two studies of breast cancer patients in
      the Bogota region. It is important that the frequency of mutations be established
      among unselected cases of breast cancer of other regions of Colombia in order to
      estimate the genetic burden of this cancer in Colombia and to plan genetic
      services. The aim of this study was to establish the mutation frequencies of the
      BRCA genes in breast cancer patients unselected for family history or age, from
      Medellin, Colombia. METHODS: We enrolled 280 unselected women with breast cancer
      from a large public hospital in Medellin, Colombia. A detailed family history
      from each patient and a blood sample was obtained and processed for DNA analysis.
      Mutations in BRCA1 and BRCA2 were sought using a combination of techniques
      including a panel of recurrent Hispanic BRCA mutations which consists of fifty
      BRCA1 mutations and forty-six BRCA2 mutations, including the five recurrent
      Colombian BRCA mutations. All mutations were confirmed by direct sequencing.
      RESULTS: Genetic testing was successfully completed for 244 of the 280 cases
      (87%). Among the 244 cases, three deleterious mutations were identified (two in
      BRCA1 and one in BRCA2) representing 1.2% of the total. The average age of breast
      cancer in the mutation-positive cases was 34 years. The two BRCA1 mutations were
      known founder mutations (3450del4 in exon 11 and A1708E in exon 18). The BRCA2
      mutation was in exon 11 (5844del5) and has not been previously reported in
      individuals of Colombian descent. Among the three mutation-positive families was
      a breast cancer family and two families with no history of breast or ovarian
      cancer. CONCLUSION: The frequency of BRCA mutations in unselected breast cancer
      cases from the Medellin region of Colombia is low and is approximately 1.2%.

PMID- 24742221
TI  - Hyperthermia-mediated local drug delivery by a bubble-generating liposomal system
      for tumor-specific chemotherapy.
AB  - As is widely suspected, lysolipid dissociation from liposomes contributes to the
      intravenous instability of ThermoDox (lysolipid liposomes), thereby impeding its
      antitumor efficacy. This work evaluates the feasibility of a thermoresponsive
      bubble-generating liposomal system without lysolipids for tumor-specific
      chemotherapy. The key component in this liposomal formulation is its encapsulated
      ammonium bicarbonate (ABC), which is used to actively load doxorubicin (DOX) into
      liposomes and trigger a drug release when heated locally. Incubating ABC
      liposomes with whole blood results in a significantly smaller decrease in the
      retention of encapsulated DOX than that by lysolipid liposomes, indicating
      superior plasma stability. Biodistribution analysis results indicate that the ABC
      formulation circulates longer than its lysolipid counterpart. Following the
      injection of ABC liposome suspension into mice with tumors heated locally,
      decomposition of the ABC encapsulated in liposomes facilitates the immediate
      thermal activation of CO2 bubble generation, subsequently increasing the
      intratumoral DOX accumulation. Consequently, the antitumor efficacy of the ABC
      liposomes is superior to that of their lysolipid counterparts. Results of this
      study demonstrate that this thermoresponsive bubble-generating liposomal system
      is a highly promising carrier for tumor-specific chemotherapy, especially for
      local drug delivery mediated at hyperthermic temperatures. 

PMID- 24742222
TI  - A study on knowledge, attitude, and practice towards premarital carrier screening
      among adults attending primary healthcare centers in a region in Oman.
AB  - BACKGROUND: Despite that hereditary diseases are widespread among the Arab
      population due to high rates of consanguineous marriages, research regarding
      community awareness towards premarital carrier screening in some countries such
      as Oman, is extremely scarce. This study aimed to investigate knowledge and
      attitude towards premarital carrier screening (PMCS) in Oman. METHODS: A cross
      sectional study was conducted using a self-administered questionnaire which was
      distributed to 400 Omani adults aged 20-35 who attended primary healthcare
      institutions at the South Batinah Governorate in Oman. RESULTS: The majority of
      the participants (84.5%) believed that PMCS was necessary, and about half of them
      (49.5%) supported the view of making PMCS compulsory. On the contrary,
      approximately one third (30.5%) of the participants reported that they were not
      in favor of taking the blood screening test. Overall, unwillingness to perform
      pre-marital testing was associated with female gender, younger age, being single,
      less education, and increased income. CONCLUSION: Despite the relatively high
      level of knowledge, about one third of the participants were still reluctant to
      carry out premarital testing. Such attitude calls for immediate need for
      community-based campaigns to encourage the public to do premarital testing.

PMID- 24742219
TI  - MicroRNAs and drug resistance in prostate cancers.
AB  - Prostate cancer is the second leading cause of cancer related death in American
      men. Androgen deprivation therapy (ADT) is used to treat patients with aggressive
      prostate cancers. After androgen deprivation therapy, prostate cancers slowly
      progress to an androgen-independent status. Taxanes (e.g., docetaxel) are used as
      standard treatments for androgen-independent prostate cancers. However, these
      chemotherapeutic agents will eventually become ineffective due to the development
      of drug resistance. A microRNA (miRNA) is a small noncoding RNA molecule, which
      can regulate gene expression at the post-transcription level. miRNAs elicit their
      effects by binding to the 3'-untranslated region (3'-UTR) of their target mRNAs,
      leading to the inhibition of translation or the degradation of the mRNAs. miRNAs
      have received increasing attention as targets for cancer therapy, as they can
      target multiple signaling pathways related to tumor progression, metastasis,
      invasion, and chemoresistance. Emerging evidence suggests that aberrant
      expression of miRNAs can lead to the development of resistant prostate cancers.
      Here, we discuss the roles of miRNAs in the development of resistant prostate
      cancers and their involvement in various drug resistant mechanisms including
      androgen signaling, apoptosis avoidance, multiple drug resistance (MDR)
      transporters, epithelialmesenchymal transition (EMT), and cancer stem cells
      (CSCs). In addition, we also discuss strategies for treating resistant prostate
      cancers by targeting specific miRNAs. Different delivery strategies are also
      discussed with focus on those that have been successfully used in human clinical
      trials. 

PMID- 24742223
TI  - Umbilical cord care in Ethiopia and implications for behavioral change: a
      qualitative study.
AB  - BACKGROUND: Infections account for up to a half of neonatal deaths in low income
      countries. The umbilicus is a common source of infection in such settings. This
      qualitative study investigates practices and perspectives related to umbilical
      cord care in Ethiopia. METHODS: In-depth interviews (IDI) were conducted in a
      district in each of the four most populous regions in the country: Oromia,
      Amhara, Tigray and Southern Nations, Nationalities and Peoples Region (SNNPR). In
      each district, one community was purposively selected; and in each study
      community, IDIs were conducted with 6 mothers, 4 grandmothers, 2 Traditional
      Birth Attendants and 2 Health Extension Workers (HEWs). The two main questions in
      the interview guide related to cord care were: How was the umbilical cord cut and
      tied? Was anything applied to the cord stump immediately after cutting/in the
      first 7 days? Why was it applied/not applied? RESULTS: The study elucidates local
      cord care practices and the rational for these practices. Concepts underlying
      cord tying practices were how to stem blood flow and facilitate delivery of the
      placenta. Substances were applied on the cord to moisturize it, facilitate its
      separation and promote healing. Locally recognized cord problems were delayed
      healing, bleeding or swelling. Few respondents reported familiarity with redness
      of the cord - a sign of infection. Grandmothers, TBAs and HEWs were influential
      regarding cord care. CONCLUSIONS: This study highlights local rationale for cord
      practices, concerns about cord related problems and recognition of signs of
      infection. Behavioral change messages aimed at improving cord care including
      cleansing with CHX should address these local perspectives. It is suggested that
      HEWs and health facility staff target mothers, grandmothers, TBAs and other
      community women with messages and counseling.

PMID- 24742224
TI  - Human rabies surveillance and control in China, 2005-2012.
AB  - BACKGROUND: Rabies reemerged in China during the 1990s with a gradual increase in
      the number and geographical dispersion of cases. As a consequence, a national
      surveillance program was introduced in 2005 to investigate the outbreak in terms
      of vaccination coverage, PEP treatment, and geographical and social composition.
      METHODS: The surveillance program was coordinated at the national level by the
      Chinese Center for Disease Control (CCDC) with data collected by regional health
      centres and provincial CCDCs, and from other official sources. Various
      statistical and multivariate analysis techniques were then used to evaluate the
      role and significance of implemented policies and strategies related to rabies
      prevention and control over this period. RESULTS: From 2005-2012, 19,221 cases
      were reported across 30 provinces, but these primarily occurred in rural areas of
      southern and eastern China, and were predominantly associated with farmers,
      students and preschool children. In particular, detailed analysis of fatalities
      reported from 2010 to 2011 shows they were associated with very low rates of post
      exposure treatment compared to the cases with standard PEP. Nevertheless,
      regulation of post-exposure prophylaxis quality, together with improved
      management and vaccination of domesticated animals, has improved prevention and
      control of rabies. CONCLUSIONS: The various control policies implemented by the
      government has played a key role in reducing rabies incidences in China. However,
      level of PEP treatment varies according to sex, age, degree and site of exposure,
      as well as the source of infection. Regulation of PEP quality together with
      improved management and vaccination of domesticated animals have also helped to
      improve prevention and control of rabies.

PMID- 24742225
TI  - Structure and conformational dynamics of a stacked dimeric G-quadruplex formed by
      the human CEB1 minisatellite.
AB  - CEB1 is a highly polymorphic human minisatellite. In yeast, the size variation of
      CEB1 tandem arrays has been associated with the capacity of the motif to form G
      quadruplexes. Here we report on the NMR solution structure of a G-quadruplex
      formed by the CEB1 DNA G-rich fragment d(AGGGGGGAGGGAGGGTGG), harboring several G
      tracts including one with six continuous guanines. This sequence forms a dimeric
      G-quadruplex involving the stacking of two subunits, each being a unique snapback
      parallel-stranded scaffold with three G-tetrad layers, three double-chain
      reversal loops, and a V-shaped loop. The two subunits are stacked at their 5'-end
      tetrads, and multiple stacking rotamers may be present due to a high symmetry at
      the stacking interface. There is a conformational exchange in the millisecond
      time scale involving a swapping motion between two bases of the six-guanine
      tract. Our results not only add to the understanding of how the G-quadruplex
      formation in human minisatellite leads to genetic instability but also address
      the fundamental questions regarding stacking of G-quadruplexes and how a long
      continuous G-tract participates in the structure and conformational dynamics of G
      quadruplexes. 

PMID- 24742226
TI  - Effects of olfactory stimulation from the fragrance of the Japanese citrus fruit
      yuzu (Citrus junos Sieb. ex Tanaka) on mood states and salivary chromogranin A as
      an endocrinologic stress marker.
AB  - OBJECTIVE: This study investigated the soothing effects of fragrance from yuzu, a
      Japanese citrus fruit (Citrus junos Sieb. ex Tanaka), with salivary chromogranin
      A (CgA) used as an endocrinologic stress marker reflecting sympathetic nervous
      system activity. METHODS: Twenty healthy women (mean age, 20.5 +/- 0.1 years)
      participated in a randomized, controlled, crossover study. Participants were
      examined on two separate occasions-once using the yuzu scent and once using
      unscented water as a control-in the follicular phase. This experiment measured
      salivary CgA and the Profile of Mood States (POMS) as a psychological index
      before and after the aromatic stimulation. RESULTS: Ten-minute inhalation of the
      yuzu scent significantly decreased salivary CgA. At 30 minutes after the
      inhalation period, the salivary CgA level further decreased. In addition, POMS
      revealed that inhalation of the aromatic yuzu oil significantly decreased total
      mood disturbance, a global measure of affective state, as well as four subscores
      of emotional symptoms (tension-anxiety, depression-dejection, anger-hostility,
      and confusion), as long as 30 minutes after the olfactory stimulation.
      CONCLUSIONS: Yuzu's aromatic effects may alleviate negative emotional stress,
      which, at least in part, would contribute to the suppression of sympathetic
      nervous system activity.

PMID- 24742227
TI  - Looking for the compass in a case of developmental topographical disorientation:
      a behavioral and neuroimaging study.
AB  - Developmental topographical disorientation (DTD) is the presence of navigational
      deficits in the context of normal intellectual ability and in the absence of any
      perinatal, neurological, or psychiatric disorder. As only three cases of DTD have
      been fully described thus far, we are still unable to draw definitive conclusions
      about its nature and relationship with other visuospatial competencies, such as
      mental rotation. The case of Mr. L.A., a 38-year-old man with no history of
      neurological or psychiatric disorders, sheds some light on these open questions.
      A neuropsychological assessment including IQ, memory, visuospatial,
      visuoconstructive, and navigational tests showed that Mr. L.A. has pure
      navigational deficits affecting both route knowledge and cognitive map
      processing. Unlike previously described cases of DTD, Mr. L.A. was not affected
      by any other visuospatial or visuoconstructive deficits. In a functional magnetic
      resonance imaging (fMRI) task involving the recall of route knowledge, Mr. L.A.
      showed activation in the occipital areas, involved in low-level perceptual
      analysis of the stimuli, and showed no activation in the areas activated in
      controls with regard to route knowledge. The present case suggests that different
      types of DTD exist, which are characterized by different navigational
      difficulties and anomalous/lacking functional brain activities in specific
      navigational networks. 

PMID- 24742228
TI  - Serious adverse events and compensation in registration trials: a review of data
      from a Japanese university hospital.
AB  - BACKGROUND: Clinical trials leading to regulatory approval, or registration
      trials, play a central role in the development of drugs and medical devices. The
      contribution of support staff, such as the clinical research coordinator (CRC)
      and administrative officers, in registration trials is now widely recognized.
      Attending to serious adverse events is an important duty of the CRC and
      investigators alike, and managing these complications and compensation
      constitutes a key responsibility. We retrospectively examined the frequency of
      serious adverse events and compensation events reported from 2007 through 2011 at
      Tokushima University Hospital, an academic hospital in rural Japan. We present
      herein the results of our analysis. RESULTS: Over the five-year period, 284
      subjects participating in 106 registration trials experienced a total of 43
      serious adverse events, and eight compensation events were documented. Among the
      serious adverse events, 35 (81.4%) were considered not related to the
      investigational drug, and 17 (39.5%) resulted in withdrawal of the study drug.
      Patients with malignant diseases experienced serious adverse events significantly
      more frequently compared to those with non-malignant diseases (28.3% versus 8.2%,
      respectively; P < 0.01). CONCLUSIONS: The CRC should be vigilant for serious
      adverse events in oncology clinical trials due to the generally higher frequency
      of these complications in subjects with malignancy. However, on an individual
      basis, the CRC may be seldom involved in the process for compensating serious
      adverse events. Therefore, the CRC's ability to share such experiences may serve
      as an opportunity for educating clinical trial support staff at the study site as
      well as those at other sites. However, further study is warranted to determine
      the role of the clinical trial support staff in optimizing methods for managing
      adverse events requiring compensation in registration trials.

PMID- 24742229
TI  - Breaking down pluripotency in the porcine embryo reveals both a premature and
      reticent stem cell state in the inner cell mass and unique expression profiles of
      the naive and primed stem cell states.
AB  - To date, it has been difficult to establish bona fide porcine embryonic stem
      cells (pESC) and stable induced pluripotent stem cells. Reasons for this remain
      unclear, but they may depend on inappropriate culture conditions. This study
      reports the most insights to date on genes expressed in the pluripotent cells of
      the porcine embryo, namely the inner cell mass (ICM), the trophectoderm-covered
      epiblast (EPI), and the embryonic disc epiblast (ED). Specifically, we reveal
      that the early porcine ICM represents a premature state of pluripotency due to
      lack of translation of key pluripotent proteins, and the late ICM enters a
      transient, reticent pluripotent state which lacks expression of most genes
      associated with pluripotency. We describe a unique expression profile of the
      porcine EPI, reflecting the naive stem cell state, including expression of OCT4,
      NANOG, CRIPTO, and SSEA-1; weak expression of NrOB1 and REX1; but very limited
      expression of genes in classical pathways involved in regulating pluripotency.
      The porcine ED, reflecting the primed stem cell state, can be characterized by
      the expression of OCT4, NANOG, SOX2, KLF4, cMYC, REX1, CRIPTO, and KLF2. Further
      cell culture experiments using inhibitors against FGF, JAK/STAT, BMP, WNT, and
      NODAL pathways on cell cultures derived from day 5 and 10 embryos reveal the
      importance of FGF, JAK/STAT, and BMP signaling in maintaining cell proliferation
      of pESCs in vitro. Together, this article provides new insights into the
      regulation of pluripotency, revealing unique stem cell states in the different
      porcine stem cell populations derived from the early developing embryo. 

PMID- 24742230
TI  - Dioscin promotes osteoblastic proliferation and differentiation via Lrp5 and ER
      pathway in mouse and human osteoblast-like cell lines.
AB  - BACKGROUND: Dioscin, a typical steroid saponin, is isolated from Dioscorea
      nipponica Makino and Dioscorea zingiberensis Wright. It has estrogenic activity
      and many studies have also reported that dioscorea plants have an effect in
      preventing and treating osteoporosis. However, the molecular mechanisms
      underlying their effect on osteoporosis treatment are poorly understood.
      Therefore, the present study aims to investigate the mechanism (s) by which
      dioscin promotes osteoblastic proliferation and differentiation in mouse pre
      osteoblast like MC3T3-E1 cells and human osteoblast-like MG-63 cells. RESULTS: We
      found that dioscin (0.25 MUg/ml, 0.5 MUg/ml, and 1.0 MUg/ml) promoted MC3T3-E1
      cells and MG-63 cells proliferation and differentiation dose dependently. Western
      blot analysis results showed that estrogen receptor alpha (ER-alpha), estrogen
      receptor beta (ER-beta), beta-catenin and Bcl-2 protein expression increased
      after MC3T3-E1 cells were treated with dioscin. Quantitative reverse
      transcription-polymerase chain reaction (RT-PCR) analysis indicated that dioscin
      could increase the ratio of osteoprotegerin (OPG)/receptor activator of NF-kappaB
      ligand (RANKL) and up-regulate the level of Lrp5 and beta-catenin. And by RNA
      interference analysis, we proved that the effect of dioscin increasing the ratio
      of OPG/RANKL was dependent on Lrp5 pathway. In addition, we also found that these
      effects of dioscin were abolished by ICI 182, 780 (100 nM), an antagonist of ER,
      indicating that an ER signaling pathway was also involved. We also found that
      dioscin (0.25 MUg/ml, 0.5 MUg/ml, and 1.0 MUg/ml) induced MG-63 cells
      proliferation and differentiation in a dose-dependent manner. Western blot
      analysis results indicated that ER-alpha, ER-beta and beta-catenin protein
      expression increased after MG-63 cells were treated with dioscin. CONCLUSIONS:
      The current study is the first to reveal that dioscin can promote osteoblasts
      proliferation and differentiation via Lrp5 and ER pathway.

PMID- 24742231
TI  - Proteomics analysis of the peritoneal dialysate effluent reveals the presence of
      calcium-regulation proteins and acute inflammatory response.
AB  - BACKGROUND: Peritoneal dialysis (PD) is a form of renal replacement used for
      advanced chronic kidney disease. PD effluent holds a great potential for
      biomarker discovery for diagnosis and prognosis. In this study a novel approach
      to unravelling the proteome of PD effluent based-on dithiothreitol depletion
      followed by 2D-SDS-PAGE and protein identification using tandem mass spectrometry
      is proposed. RESULTS: A total of 49 spots were analysed revealing 25 proteins
      differentially expressed, among them many proteins involved in calcium
      regulation. CONCLUSIONS: Remarkably, a group of proteins dealing with calcium
      metabolism and calcium regulation has been found to be lost through peritoneal
      dialysate effluent, giving thus a potential explanation to the calcification of
      soft tissues in patients subjected to peritoneal dialysis and kidney injury.
      Comparison of literature dealing with PD is difficult due to differences in
      sample treatment and analytical methodologies.

PMID- 24742232
TI  - Routine diagnostic ureteroscopy for suspected upper tract transitional-cell
      carcinoma.
AB  - BACKGROUND AND PURPOSE: Upper tract transitional-cell carcinoma (utTCC) is
      uncommon. Standard evaluation includes imaging, cytology, and cystoscopy and gold
      standard treatment is nephroureterectomy (NU) with solid oncologic outcomes and
      elevated morbidity. In this study, we report on the value of including routine
      ureteroscopy (URS) for evaluating suspected utTCC in shifting the treatment
      toward less morbid options and increasing preoperative diagnostic accuracy.
      PATIENTS AND METHODS: Records of patients presenting between 2002 and 2013 with
      suspected utTCC were reviewed. Since 2010, URS has been included routinely in the
      evaluation protocol. Demographic, clinical, and pathologic characteristics were
      recorded and compared between earlier experience (group 1) and with routine URS
      (group 2). In addition, the number needed to treat (NNT) was calculated with
      respect to shifting the procedure choice from NU to other options as well as in
      reducing the rates of misdiagnoses. RESULTS: A total of 118 patients were
      included: 63 in group 1 and 55 in group 2. The pathology-confirmed TCC rates were
      comparable between the two groups (78 vs 85%). The rates of NU decreased with
      routine URS use from 89% to 69% (P=0.011, NNT=5.05) whereby patients were treated
      endoscopically or with distal ureterectomy. Misdiagnoses decreased from 15.5% to
      2.1% with routine URS (P=0.021, NNT=7.44). Sepsis occurred in two patients after
      URS. CONCLUSIONS: In this initial study, routine URS evaluation for suspected
      utTCC appears to enable an increased use of other treatment choices rather then
      NU, with an estimated five URS avoiding one NU. Moreover, routine URS reduced the
      rates of misdiagnosis of TCC. Complications associated with URS may add an
      additional morbidity burden, however.

PMID- 24742242
TI  - Evaluation of Darkroom disease's symptoms among radiographers in the West Bank
      hospitals: a cross-sectional study in Palestine.
AB  - BACKGROUND: Radiographers report many unexplained work related symptoms
      attributed to "darkroom disease symptoms" such as headache, skin rash, mouth
      sores, blurred vision, palpitation, and chemical taste. The aim of the present
      study was to assess the prevalence of occupationally-related darkroom disease
      symptoms among male radiographers in the West Bank hospitals. METHODS: A cross
      sectional study was conducted on a non-random purposive sample of male
      radiographers (study group) and nurses (control group) using a previously
      validated and standardized questionnaire. RESULTS: We were able to recruit 330
      radiographers and 242 nurses. Data analysis showed that the majority of both
      groups aged between (36-43) years. Furthermore, the differences in the reported
      prevalence of symptoms among radiographers showed a statistically significant
      higher percentage for each reported symptom compared to nurses (P-values <0.001).
      In multivariate linear regression, staying more than 30 minutes in the darkroom
      per shift was associated with a significant increase in the mean number of
      reported symptoms (P-value < 0.001). However, the availability of a ventilating
      machine in the darkroom showed a strong negative association with the mean number
      of reported symptoms (P-value < 0.001). CONCLUSIONS: Our findings could help
      overcome the limitations usually encountered in such complex occupational
      exposure. However, trying to interpret our finding directly to chemicals exposure
      in the radiographers' occupational setting should be done with caution due to the
      absence of active or passive monitoring for the suspected chemicals.

PMID- 24742243
TI  - High performance and bendable few-layered InSe photodetectors with broad spectral
      response.
AB  - Two-dimensional crystals with a wealth of exotic dimensional-dependent properties
      are promising candidates for next-generation ultrathin and flexible
      optoelectronic devices. For the first time, we demonstrate that few-layered InSe
      photodetectors, fabricated on both a rigid SiO2/Si substrate and a flexible
      polyethylene terephthalate (PET) film, are capable of conducting broadband
      photodetection from the visible to near-infrared region (450-785 nm) with high
      photoresponsivities of up to 12.3 AW(-1) at 450 nm (on SiO2/Si) and 3.9 AW(-1) at
      633 nm (on PET). These photoresponsivities are superior to those of other
      recently reported two-dimensional (2D) crystal-based (graphene, MoS2, GaS, and
      GaSe) photodetectors. The InSe devices fabricated on rigid SiO2/Si substrates
      possess a response time of ~50 ms and exhibit long-term stability in
      photoswitching. These InSe devices can also operate on a flexible substrate with
      or without bending and reveal comparable performance to those devices on SiO2/Si.
      With these excellent optoelectronic merits, we envision that the nanoscale InSe
      layers will not only find applications in flexible optoelectronics but also act
      as an active component to configure versatile 2D heterostructure devices. 

PMID- 24742241
TI  - Ghrelin accelerates synapse formation and activity development in cultured
      cortical networks.
AB  - BACKGROUND: While ghrelin was initially related to appetite stimulation and
      growth hormone secretion, it also has a neuroprotective effect in
      neurodegenerative diseases and regulates cognitive function. The cellular basis
      of those processes is related to synaptic efficacy and plasticity. Previous
      studies have shown that ghrelin not only stimulates synapse formation in cultured
      cortical neurons and hippocampal slices, but also alters some of the
      electrophysiological properties of neurons in the hypothalamus, amygdala and
      other subcortical areas. However, direct evidence for ghrelin's ability to
      modulate the activity in cortical neurons is not available yet. In this study, we
      investigated the effect of acylated ghrelin on the development of the activity
      level and activity patterns in cortical neurons, in relation to its effect on
      synaptogenesis. Additionally, we quantitatively evaluated the expression of the
      receptor for acylated ghrelin--growth hormone secretagogue receptor-1a (GHSR-1a)
      during development. RESULTS: We performed electrophysiology and
      immunohistochemistry on dissociated cortical cultures from neonates, treated
      chronically with acylated ghrelin. On average 76+/-4.6% of the cortical neurons
      expressed GHSR-1a. Synapse density was found to be much higher in ghrelin treated
      cultures than in controls across all age groups (1, 2 or 3 weeks). In all
      cultures (control and ghrelin treated), network activity gradually increased
      until it reached a maximum after approximately 3 weeks, followed by a slight
      decrease towards a plateau. During early developmental stages (1-2 weeks), the
      activity was much higher in ghrelin treated cultures and consequently, they
      reached the plateau value almost a week earlier than controls. CONCLUSIONS:
      Acylated ghrelin leads to earlier network formation and activation in cultured
      cortical neuronal networks, the latter being a possibly consequence of
      accelerated synaptogenesis.

PMID- 24742244
TI  - S100A4 is an independent prognostic factor for patients with lung cancer: a meta
      analysis.
AB  - OBJECTIVE: To evaluate the association of S100A4 levels with the prognosis of
      lung cancer (LC). METHODS: The RevMan 5.0 software was utilized to perform
      literature retrieval, data collection, and statistical analysis according to its
      guidelines. Literature-based searching was guided to gather data, and the fixed
      effect model was used to pool the hazard ratio (HR) in this study. RESULTS: A
      total of 10 eligible studies that included 1364 LC patients were analyzed. About
      72.6% of patients had positive expression of S100A4 according to the criteria
      defined by the authors. The HR of positive expression for overall survival (OS)
      was 1.30 times of that of negative expression in LC patients (HR=1.30, 95%
      confidence interval: 1.04 to 1.61, p=0.02). CONCLUSION: Patients with positive
      expression of S100A4 appear to have a poorer OS compared with those with negative
      expression of S100A4.

PMID- 24742245
TI  - Coexisting surface phases and coherent one-dimensional interfaces on BaTiO3(001).
AB  - Coexistence of surface reconstructions is important due to the diversity in
      kinetic and thermodynamic processes involved. We identify the coexistence of
      kinetically accessible phases that are chemically identical and form coherent
      interfaces. Here, we establish the coexistence of two phases, c(2 * 2) and c(4 *
      4), in BaTiO3(001) with atomically resolved Scanning Tunneling Microscopy (STM).
      First-principles thermodynamic calculations determine that TiO adunits and
      clusters compose the surfaces. We show that TiO diffusion results in a
      kinetically accessible c(2 * 2) phase, while TiO clustering results in a
      kinetically and thermodynamically stable c(4 * 4) phase. We explain the formation
      of domains based on the diffusion of TiO units. The diffusion direction
      determines the observed 1D coherent interfaces between c(2 * 2) and c(4 * 4)
      reconstructions. We propose atomic models for the c(2 * 2), c(4 * 4), and 1D
      interfaces. 

PMID- 24742246
TI  - Investigation of the electronic structures of organolanthanide sandwich complex
      anions by photoelectron spectroscopy: 4f orbital contribution in the metal-ligand
      interaction.
AB  - The electronic structures of lanthanide (Ln) ions sandwiched between 1,3,5,7
      cyclooctatetraene (COT), Ln(COT)2(-), have been investigated by anion
      photoelectron spectroscopy. Complexes of 12 Ln atoms were investigated (excluding
      promethium (Pm), europium (Eu), and ytterbium (Yb)). The 213 nm photoelectron
      (PE) spectra of Ln(COT)2(-) exhibit two peaks assignable to the highest occupied
      molecular orbital (HOMO; e2u) and the next HOMO (HOMO-1; e2g) approximately at
      2.6 and 3.6 eV, respectively, and their energy gap increases as the central metal
      atom progresses from lanthanum (La) to lutetium (Lu). Since lanthanide
      contraction shortens the distance between the Ln atom and the COT ligands, the
      widening energy gap represents the destabilization of the e2u orbital as well as
      the stabilization of the e2g orbital. Evidence for 4f orbital contribution in the
      metal-ligand interaction has been revealed by the Ln atom dependence in which the
      same e2u orbital symmetry enables an interaction between the 4f orbital of Ln
      atoms and the pi orbital of COT. 

PMID- 24742248
TI  - A Multicenter prospective study of poor-grade aneurysmal subarachnoid hemorrhage
      (AMPAS): observational registry study.
AB  - BACKGROUND: Poor-grade aneurysmal subarachnoid hemorrhage (aSAH) is associated
      with very high mortality and morbidity. Our limited knowledge on predictors of
      long-term outcome in poor-grade patients with aSAH definitively managed comes
      from retrospective and prospective studies of small case series of patients in
      single center. The purpose of the AMPAS is to determine the long-term outcomes in
      poor-grade patients with different managements within different time after aSAH,
      and identify the independent predictors of the outcome that help guide the
      decision on definitive management. METHODS/DESIGN: The AMPAS study is a
      prospective, multicenter, observational registry of consecutive hospitalized
      patients with poor grade aSAH (WFNS grade IV and V). The aim is to enroll at
      least 226 poor-grade patients in 11 high-volume medical centers (eg, >150 aSAH
      cases per year) affiliated to different universities in China. This study will
      describe poor grade patients and aneurysm characteristics, treatment strategies
      (modality and time of definitive management), hospitalization complications and
      outcomes evolve over time. The definitive management is ruptured aneurysm
      treatment. Outcomes at 3, 6, 12 months after the management were measured using
      the Glasgow Outcome Scale and the Modified Rankin Scale. DISCUSSION: The AMPAS is
      the first prospective, multicenter, observational registry of poor grade aSAH
      with any management. This study will contribute to a better understanding of
      significant predictors of outcome in poor grade patients and help guide future
      treatment of the worst patients after aSAH. TRIAL REGISTRATION: Chinese Clinical
      Trial Registry: ChiCTR-TNRC-10001041.

PMID- 24742249
TI  - Antimicrobial stewardship program prompts increased and earlier infectious
      diseases consultation.
AB  - A recent analysis demonstrated that infectious diseases (ID) specialty
      intervention was associated with decreased mortality and hospital readmission.
      These benefits were greatest if involvement occurred within two days of hospital
      admission. Antimicrobial stewardship programs should augment the services of an
      ID specialist team and promote formal consultation. Implementation of an
      antimicrobial stewardship program at the Providence Veterans Affairs Medical
      Center was associated with an increased number of consults (increase of 72.2%)
      and decreased time to consult (3.5 days sooner), which might also dramatically
      improve patient outcomes, including mortality and readmission rates. 

PMID- 24742250
TI  - Body mass index and waist/height ratio for prediction of severity of coronary
      artery disease.
AB  - BACKGROUND: To determine whether waist-to-height ratio correlates with coronary
      artery disease (CAD) severity better, than the body mass index (BMI) as assessed
      by coronary angiography in Bangladeshi population. METHODS: This cross sectional
      study was done on patients in Department of Cardiology in DMCH and those referred
      in the cath-lab of the Department of Cardiology for CAG during November 2009 to
      October 2010 involving 120 patients. They were divided into group-A (with
      coronary score >=7) and group-B (coronary score <7) depending on Gensisni score.
      RESULT: There were no statistically significant difference regarding the
      distribution of age, sex and clinical diagnosis and parameters between the two
      groups. The mean age of patients was 51.7 +/- 8.2 years and 48.8 +/- 9.1 years in
      Group A and Group B respectively with a male predominance in both the groups.
      Patients in group A had higher BMI >=25 and waist to height ratio (>=0.55) than
      Group B which showed a statistically significant association (p < 0.001). Though
      a significant positive correlation (r = 0.296, p = 0.006) was observed between
      BMI and Coronary artery disease score in group A patients, scenario was reverse
      fro group B (r = 0.076, p = 0.659). The statement was also true for Waist-to
      height ratio and Waist-to-height ratio with BMI. Multivariate analysis also
      yeilded that a patient with BMI >=25 kg/m2 and waist-to height ratio of >=0.55
      are 3.06 times and 6.77 times, more likely to develop significant coronary artery
      disease respectively. CONCLUSION: The waist-to-height ratio showed better
      correlation with the severity of coronary artery disease than the BMI.

PMID- 24742251
TI  - Expression of indoleamine 2,3-dioxygenase and infiltration of FOXP3+ regulatory T
      cells are associated with aggressive features of papillary thyroid
      microcarcinoma.
AB  - BACKGROUND: Indoleamine 2,3-dioxygenase (IDO) is overexpressed in many different
      types of tumor and is associated with activation of FOXP3+ regulatory T cells
      (Treg cells) and downregulation of cytotoxic cellular immunity in the tumor
      microenvironment. It has been suggested that IDO inhibitors can be utilized as an
      effective therapeutic agent against human cancers. However, the expression of IDO
      and its association with tumor-infiltrating lymphocytes (TILs) remain unclear in
      papillary thyroid microcarcinoma (PTMC). METHODS: Immunohistochemical staining
      for IDO expression was performed on 124 PTMC samples. TIL subsets (CD3+, CD8+,
      and FOXP3+ T cells) were counted in serial sections. The relationships between
      the expression of IDO and infiltration of TIL subsets, as well as the
      relationships between these immunomodulating factors and clinicopathologic
      parameters of PTMCs, were analyzed. RESULTS: There was a significant correlation
      between IDO expression and reduced CD3+ TIL and increased FOXP3+ TIL. IDO
      expression was found in 31% of PTMC and was associated with aggressive
      clinicopathologic features of the tumor such as extrathyroidal extension (ETE)
      and multifocality. High infiltration of FOXP3+ Treg cells in the tumor was
      associated with lymph node metastasis, ETE, and multifocality. Furthermore, high
      FOXP3/CD8+ ratio was associated with multifocality and lymph node metastasis, and
      high FOXP3+/CD3+ ratio was related to ETE and multifocality. In multivariate
      analyses, IDO expression was found to be an independent predictive factor for ETE
      and tumor multifocality. CONCLUSIONS: IDO expression and infiltration of FOXP3+
      Treg cells were closely related to each other and were associated with aggressive
      features of PTMC, suggesting that disruption of antitumor immunity by IDO
      expression, and thus, infiltration of FOXP3+ Treg cells may contribute to tumor
      progression in PTMC.

PMID- 24742252
TI  - Animal models of enterovirus 71 infection: applications and limitations.
AB  - Human enterovirus 71 (EV71) has emerged as a neuroinvasive virus that is
      responsible for several outbreaks in the Asia-Pacific region over the past 15
      years. Appropriate animal models are needed to understand EV71 neuropathogenesis
      better and to facilitate the development of effective vaccines and drugs. Non
      human primate models have been used to characterize and evaluate the
      neurovirulence of EV71 after the early outbreaks in late 1990s. However, these
      models were not suitable for assessing the neurovirulence level of the virus and
      were associated with ethical and economic difficulties in terms of broad
      application. Several strategies have been applied to develop mouse models of EV71
      infection, including strategies that employ virus adaption and immunodeficient
      hosts. Although these mouse models do not closely mimic human disease, they have
      been applied to determine the pathogenesis of and treatment and prevention of the
      disease. EV71 receptor-transgenic mouse models have recently been developed and
      have significantly advanced our understanding of the biological features of the
      virus and the host-parasite interactions. Overall, each of these models has
      advantages and disadvantages, and these models are differentially suited for
      studies of EV71 pathogenesis and/or the pre-clinical testing of antiviral drugs
      and vaccines. In this paper, we review the characteristics, applications and
      limitation of these EV71 animal models, including non-human primate and mouse
      models.

PMID- 24742253
TI  - Dynamic introduction of cell adhesive factor via reversible multicovalent
      phenylboronic acid/cis-diol polymeric complexes.
AB  - In this work, dynamic introduction of bioactive RGD peptide on a matrix was
      successfully demonstrated via reversible multicovalent interactions within
      PBA/cis-diol polymeric complexes. These reversible, stable multiple interaction
      sites, in addition to a long accessible polymeric linker, enabled "reversible"
      control of cell adhesion by specific biomolecular exchange (e.g., glucose or
      fructose). This biomolecule-triggered, noninvasive strategy shows great promise
      for use in real-time biological research and mimics natural biomolecular feedback
      systems, thus having potential application in medical diagnoses and regenerative
      medicine. 

PMID- 24742254
TI  - Cyclohexadepsipeptides of the isaridin class from the marine-derived fungus
      Beauveria felina EN-135.
AB  - Three new cyclohexadepsipeptides of the isaridin class including isaridin G (1),
      desmethylisaridin G (2), and desmethylisaridin C1 (3), along with three related
      known metabolites (4-6), were isolated and identified from the marine bryozoan
      derived fungus Beauveria felina EN-135. The structures of these compounds were
      elucidated on the basis of extensive spectroscopic analysis, and the structures
      and absolute configurations of compounds 1-3 were confirmed by single-crystal X
      ray diffraction analysis. The crystal structures showed the presence of beta
      turns for the Tyr(3)/N-Me-Val(4) and Phe(3)/N-Me-Val(4) amide bonds in compounds
      2 and 3, respectively, in the cis conformations, which were opposite other
      reported isaridins. The conformations of the HMPA(1)-Pro(2) amide bond in
      compound 2 are different in the solution and in the crystal structures, which
      showed trans and cis geometries, respectively, while compounds 1 and 3 do not
      exhibit this phenomenon. Each of the isolated compounds was evaluated for
      antimicrobial activity and brine shrimp lethality. Compound 3 exhibited
      antibacterial activity against E. coli with an MIC value of 8 MUg/mL. 

PMID- 24742255
TI  - Interactions during feeding with mothers and their infants with symptoms of
      gastroesophageal reflux.
AB  - OBJECTIVES: To examine whether maternal-child interaction during feedings was
      suboptimal in dyads in which the infant had gastroesophageal reflux disease
      (GERD) and to compare massage therapy to a nonmassage therapy sham treatment in
      improving the mother-child interaction in these dyads. DESIGN: In this
      randomized, controlled pilot study, infants received massage therapy (n=18) or a
      nonmassage touch/holding sham treatment (n=18). Mothers, data collectors, and the
      investigator who scored the feeding observations were blinded to group
      assignment. SETTINGS/LOCATION: Dyads were recruited from pediatric care providers
      in the Denver metropolitan area and online advertisements at the University of
      Colorado. Treatments were given in the home of the dyad. PARTICIPANTS: Healthy
      infants, born at 38-42 weeks gestational age, were 5-10 weeks of age at
      enrollment; had a score of at least 16 on the Infant Gastroesophageal Reflux
      Questionnaire-Revised; and were diagnosed with GERD by their pediatric provider.
      Mothers were English speaking and at least 18 years of age. INTERVENTIONS:
      Treatments were given for 30 minutes twice weekly for 6 weeks. A certified infant
      massage therapist administered massage, and a registered nurse or physical
      therapist experienced with infants administered the control treatment. OUTCOME
      MEASURES: Maternal and infant scores on the Nursing Child Assessment of Feeding
      Scale (NCAFS). RESULTS: NCAFS scores were significantly lower than national
      norms. Small to moderately sized effects showing improvement in the massage group
      relative to the nonmassage group were seen for Sensitivity to Cues, Social
      Emotional Growth Fostering, Cognitive Growth Fostering, and Clarity of Cues
      (Cohen d) and ranged from 0.24 to 0.56. CONCLUSIONS: Mothers and infants with
      GERD experience significantly worse interactions than those without GERD. Massage
      given twice weekly by a professional trended toward improved interaction during
      feeding. Daily maternal administration of massage may have a positive effect on
      the relationship.

PMID- 24742257
TI  - Impacts of mobility disability and high and increasing body mass index on health
      related quality of life and participation in society: a population-based cohort
      study from Sweden.
AB  - BACKGROUND: Increasing obesity in adults with mobility disability has become a
      considerable health problem, similar to the increasing trend of obesity in the
      general population. The aims of this study were to investigate the association of
      mobility disability with overweight status and obesity in a large population
      based Swedish cohort of adults, and to investigate whether mobility disability,
      high body mass index (BMI), and increasing BMI over time are predictors of health
      related quality of life and participation in society after 8 years of follow-up.
      METHODS: The study cohort included 13,549 individuals aged 18-64 years who
      answered questions about mobility disability, weight, height, health-related
      quality of life and participation in society in the Stockholm Public Health
      Survey 2002 and 2010. The cohort was randomly selected from the population of
      Stockholm County, and divided into six subgroups based on data for mobility
      disability and overweight status. Multiple binary logistic regression analyses
      were performed to assess the likelihood for low health-related quality of life
      and lack of participation. RESULTS: Respondents with mobility disability had a
      higher mean BMI than those without mobility disability. Respondents both with and
      without mobility disability increased in BMI, but with no significant difference
      in the longitudinal changes (mean difference: 0.078; 95% CI: -0.16 - 0.32).
      Presence of mobility disability increased the risk of low health-related quality
      of life and lack of participation in 2010, irrespective of low health-related
      quality of life and lack of participation in 2002. The risk of pain and low
      general health (parts of health-related quality of life) increased for every 5
      units of higher BMI reported in 2010. In respondents without low general health
      at baseline, the risk of obtaining low general health increased for every 5 units
      of higher BMI in 2010 (OR:1.60; CI: 1.47 - 1.74). CONCLUSIONS: The greatest risk
      of low general health after 8 years was observed for respondents with both
      mobility disability and high BMI. These results indicate the importance of
      working preventively with persons with mobility disability and overweight status
      or obesity based on the risk of further weight gain.

PMID- 24742256
TI  - On the potential of acarbose to reduce cardiovascular disease.
AB  - In the emerging landscape of cardiovascular (CV) outcome trials evaluating the
      effects of blood glucose lowering drugs in individuals with type 2 diabetes, it
      is becoming increasingly apparent that since the promising signals coming from
      the United Kingdom Prospective Diabetes Study (UKPDS) no unequivocal benefits
      have been established for any single therapy thus far. There is an unmet need for
      introducing an effective pharmacological agent which could target both correlates
      of glycaemic regulation and CV risk factors, to ameliorate the enormous burden of
      fatal and non-fatal CV events in diabetic patients. Acarbose, like other alpha
      glucosidase inhibitors (AGIs), has been proven to be an effective antidiabetic
      treatment for decades, but the overall significant impact of this class of drugs
      on modulating CV risk has only recently been appreciated. Accumulating evidence
      has shown that apart from its multiple effects on primarily postprandial glucose
      dysmetabolism, a key component of mechanisms linked to increased incidence of CV
      events, acarbose therapy also associates with a favorable impact on an array of
      surrogate markers of CV disease. Data stemming from in vitro testing of human
      cell lines as well as from preliminary trials in diabetic populations, like the
      Study to Prevent Non-Insulin-Dependent Diabetes Mellitus (STOP-NIDDM) trial, have
      highlighted - though not undisputed - the potential beneficial effects of the
      drug on CV morbidity. Large scale trials, like the ongoing Acarbose
      Cardiovascular Evaluation (ACE) trial, aim at conclusively establishing such a
      positive effect in patients with coronary heart disease and impaired glucose
      tolerance. In view of its usually acceptable level of side effects that are, if
      they occur, mostly limited to transient gastrointestinal symptoms, acarbose could
      well be a strong future player in CV disease secondary prevention. Current
      discouraging results from many trials of antidiabetic medications to
      significantly lower CV event rates in diabetic patients, should only draw further
      attention on alternative glucose lowering agents, among which acarbose is indeed
      promising. 

PMID- 24742258
TI  - Multi-surface modeling to predict free zinc ion concentrations in low-zinc soils.
AB  - Multi-surface models are widely used to assess the potential ecotoxicological
      risk in metal-contaminated soils. Their accuracy in predicting metal speciation
      in soils with low metal levels was not yet tested. Now highly sensitive
      analytical techniques are available to experimentally validate such models at low
      concentration levels. The objective of this study was to test the accuracy of a
      multi-surface model to predict the Zn(2+) concentration and to improve our
      understanding of Zn bioavailability in low-Zn soils. High-Zn soils were included
      as controls. Model parameters were determined independently on the basis of
      earlier peer-reviewed publications. Model output was validated against free
      Zn(2+) concentrations determined with the soil column Donnan membrane technique
      in a range of soils varying in potentially available Zn, organic matter, clay
      silicate, and iron (hydr)oxide contents and pH. Deviations between predicted
      Zn(2+) concentrations and experimentally determined values over the whole Zn
      concentration range were less or equal to the experimental standard error, except
      for one low-Zn soil. The Zn(2+) concentration was mainly controlled by
      adsorption, where organic matter was predicted to be the dominant soil sorbent.
      The predicted Zn(2+) concentration depends more sensitively upon changes of the
      reactive Zn pool (application of 0.6, 1.2, 2.4, and 3.6 mg of Zn kg(-1) of soil)
      and organic matter content (+/- 0.2 and 0.4%) than pH changes (+/- 0.5 and 1 pH
      unit).

PMID- 24742259
TI  - Laparoscopic treatment of symptomatic urachal remnants in children.
AB  - PURPOSE: To evaluate laparoscopic treatment of symptomatic urachal remnants in
      children, the authors review their experience analyzing different approaches and
      results obtained in a 8-year period. PATIENTS AND METHODS: From July 2005 to
      September 2013, 12 children underwent 13 interventions for treatment of
      symptomatic urachal remnants. In four patients, the technique was a laparoscopic
      assisted removal of the remnant, in two patients, a laparoscopic-assisted
      drainage of an urachal abscess, and in seven patients, a laparoscopic excision of
      the remnant. One patient underwent a double intervention-laparoscopic drainage of
      an infected urachal remnant and its delayed laparoscopic excision. RESULTS: The
      laparoscopic-assisted removal of the urachal remnant was performed in two cases
      of infected urachal sinus, in one case of symptomatic sinus, and in one cases of
      infected urachal cyst. The laparoscopic-assisted drainage of urachal abscesses
      was performed in two patients: In one patient, the abscess was because of an
      infected sinus while in the other patient, the abscess was caused by an infected
      cyst. Of the seven patients treated with pure laparoscopic technique, one had a
      symptomatic sinus, another had an association between a symptomatic urachal sinus
      and an urachal cyst, and five patients had a symptomatic urachal cyst. In all
      cases, intraoperative or postoperative complications and recurrences did not
      occur, and the cosmetic results were good. Follow-up ranged from 6 months to 8
      years and 8 months. CONCLUSION: Laparoscopic surgery for symptomatic urachal
      remnants is safe and reliable in cases of drainage of urachal abscess and in
      cases of excision of the remnant. Laparoscopy allows a radical excision of the
      remnants with all the advantages of this procedure. In case of conversion,
      laparoscopic-assisted technique with minimal incision could be a good alternative
      to open surgery.

PMID- 24742260
TI  - In-situ synthesis of carbon nanotube-graphite electronic devices and their
      integrations onto surfaces of live plants and insects.
AB  - Here we report an unconventional approach for the single-step synthesis of
      monolithically integrated electronic devices based on multidimensional carbon
      structures. Integrated arrays of field-effect transistors and sensors composed of
      carbon nanotube channels and graphitic electrodes and interconnects were formed
      directly from the synthesis. These fully integrated, all-carbon devices are
      highly flexible and can be transferred onto both planar and nonplanar substrates,
      including papers, clothes, and fingernails. Furthermore, the sensor network can
      be interfaced with inherent life forms in nature for monitoring environmental
      conditions. Examples of significant applications are the integration of the
      devices to live plants or insects for real-time, wireless sensing of toxic gases.

PMID- 24742261
TI  - 3,5-Dinitrobenzoic acid-capped upconverting nanocrystals for the selective
      detection of melamine.
AB  - In this Research Article, we report for the first time the use of upconverting
      nanoparticles to detect melamine up to nanomolar concentration. Detection of
      melamine is important as it is one of the adulterant in protein rich food
      products due to its high nitrogen content. In this work, we have shown how the
      electron deficient 3,5-dinitrobenzoic acid (DNB)-coated Er/Yb-NaYF4 nanocrystals
      can specifically bind to electron rich melamine and alter the upconverting
      property of the nanocrystals. This selective binding led to the quenching of the
      upconversion emission from the nanocrystals. The high selectivity is verified by
      the addition of various analytes similar in structure with that of melamine. In
      addition, the selective quenching of the upconversion emission is reversible with
      the addition of dilute acid. This process has been repeated for more than five
      cycles with only a slight decrease in the sensing ability. The study was also
      extended to real milk samples, where the milk adulterated with melamine quenches
      the emission intensity of the DNB coated NaYF4:Er/Yb nanocrystals, whereas hardly
      any change is noted for the unadulterated milk sample. The high robustness and
      the sharp emission peaks make Er(3+)/Yb(3+)-doped NaYF4 nanocrystals a potential
      melamine sensing material over other organic fluorophores and nanocrystals
      possessing broad emissions. 

PMID- 24742262
TI  - Genetic analysis of tolerance to the root lesion nematode Pratylenchus neglectus
      in the legume Medicago littoralis.
AB  - BACKGROUND: The nematode Pratylenchus neglectus has a wide host range and is able
      to feed on the root systems of cereals, oilseeds, grain and pasture legumes.
      Under the Mediterranean low rainfall environments of Australia, annual Medicago
      pasture legumes are used in rotation with cereals to fix atmospheric nitrogen and
      improve soil parameters. Considerable efforts are being made in breeding programs
      to improve resistance and tolerance to Pratylenchus neglectus in the major crops
      wheat and barley, which makes it vital to develop appropriate selection tools in
      medics. RESULTS: A strong source of tolerance to root damage by the root lesion
      nematode (RLN) Pratylenchus neglectus had previously been identified in line RH-1
      (strand medic, M. littoralis). Using RH-1, we have developed a single seed
      descent (SSD) population of 138 lines by crossing it to the intolerant cultivar
      Herald. After inoculation, RLN-associated root damage clearly segregated in the
      population. Genetic analysis was performed by constructing a genetic map using
      simple sequence repeat (SSR) and gene-based SNP markers. A highly significant
      quantitative trait locus (QTL), QPnTolMl.1, was identified explaining 49% of the
      phenotypic variation in the SSD population. All SSRs and gene-based markers in
      the QTL region were derived from chromosome 1 of the sequenced genome of the
      closely related species M. truncatula. Gene-based markers were validated in
      advanced breeding lines derived from the RH-1 parent and also a second RLN
      tolerance source, RH-2 (M. truncatula ssp. tricycla). Comparative analysis to
      sequenced legume genomes showed that the physical QTL interval exists as a
      synteny block in Lotus japonicus, common bean, soybean and chickpea. Furthermore,
      using the sequenced genome information of M. truncatula, the QTL interval
      contains 55 genes out of which five are discussed as potential candidate genes
      responsible for the mapped tolerance. CONCLUSION: The closely linked set of SNP
      based PCR markers is directly applicable to select for two different sources of
      RLN tolerance in breeding programs. Moreover, genome sequence information has
      allowed proposing candidate genes for further functional analysis and nominates
      QPnTolMl.1 as a target locus for RLN tolerance in economically important grain
      legumes, e.g. chickpea.

PMID- 24742263
TI  - Higher prevalence of obesity and overweight without an adverse metabolic profile
      in girls with central precocious puberty compared to girls with early puberty,
      regardless of GnRH analogue treatment.
AB  - OBJECTIVES: 1. To determine BMI, obesity/overweight rates, glucose and lipids at
      baseline, during GnRHa treatment and shortly after therapy discontinuation in
      female children with CPP and EP. 2. To compare this response to that seen in a
      similar group of untreated patients. METHODS: A retrospective analysis of 71
      children with either CPP (n = 37) or EP (n = 34) was undertaken. Forty three were
      treated with a GnRHa for at least 2 years, while 28 were followed without
      treatment. RESULTS: At the time of diagnosis, a higher BMI (z-score of 1.1 +/-
      0.8 vs. 0.6 +/- 0.7, p = 0.004) and a higher prevalence of obesity/overweight
      (72.9 vs. 35.3%, p = 0.001) was observed in subjects with CPP when compared to
      those with EP. Children with EP had higher fasting glucose and total cholesterol
      than those with CPP. BMI z-score, obesity/overweight rates, fasting glucose and
      lipids did not change significantly in girls with CPP or EP during 3 yrs of
      follow up, regardless of treatment. Weight z-scores were higher at 3 years in
      treated than in untreated girls with CPP (p = 0.02), while it was higher in
      untreated than in GnRHa-treated patients with EP at baseline, 1, 2 and 3 years (p
      = 0.007, p = 0.002, p = 0.02 and p = 0.04, respectively) and remained so shortly
      after stopping therapy (p = 0.03). CONCLUSIONS: There is a high prevalence of
      obesity/overweight in girls with CPP and EP at diagnosis. However, this risk is
      greater in CPP than in EP girls. BMI, Obesity/overweight rates, fasting glucose
      and lipids remained stable in CPP and EP girls regardless of therapy. Weight z
      scores were found to be higher in treated CPP girls and in untreated girls with
      EP.

PMID- 24742264
TI  - Examination of the Factor Structure of the Adolescent Sleep-Wake Scale (ASWS).
AB  - This study examined the factor structure of the Adolescent Sleep-Wake Scale
      (ASWS) among 491 adolescents (12-18 years) with and without pediatric health
      conditions. Exploratory factor analyses were conducted using iterated principal
      axis factoring with varimax rotation. Highly cross-loading items were
      systematically removed and analyses were rerun until a clean solution was
      attained. The final solution explained 57.1% of the total model variance,
      including 10 items and three factors: Falling Asleep and Reinitiating Sleep
      Revised, returning to Wakefulness-Revised, and Going to Bed-Revised. Internal
      consistency reliability scores were acceptable to good, with the exception of the
      Going to Bed-Revised subscale for the healthy sample. Adolescents with chronic
      pain reported significantly poorer overall sleep quality and more problems in
      falling asleep, reinitiating sleep, and returning to wakefulness as compared to
      healthy adolescents, providing preliminary evidence for construct validity of the
      new factors. The resulting ASWS version is a concise assessment tool with
      empirically derived, distinct behavioral sleep dimensions that can be used for
      clinical and research purposes. 

PMID- 24742265
TI  - Associations of physical activity, fitness, and body composition with heart rate
      variability-based indicators of stress and recovery on workdays: a cross
      sectional study.
AB  - BACKGROUND: The purpose of this study was to investigate how physical activity
      (PA), cardiorespiratory fitness (CRF), and body composition are associated with
      heart rate variability (HRV)-based indicators of stress and recovery on workdays.
      Additionally, we evaluated the association of objectively measured stress with
      self-reported burnout symptoms. METHODS: Participants of this cross-sectional
      study were 81 healthy males (age range 26-40 y). Stress and recovery on workdays
      were measured objectively based on HRV recordings. CRF and anthropometry were
      assessed in laboratory conditions. The level of PA was based on a detailed PA
      interview (MET index [MET-h/d]) and self-reported activity class. RESULTS: PA,
      CRF, and body composition were significantly associated with levels of stress and
      recovery on workdays. MET index (P < 0.001), activity class (P = 0.001), and CRF
      (P = 0.019) were negatively associated with stress during working hours whereas
      body fat percentage (P = 0.005) was positively associated. Overall, 27.5% of the
      variance of total stress on workdays (P = 0.001) was accounted for by PA, CRF,
      and body composition. Body fat percentage and body mass index were negatively
      associated with night-time recovery whereas CRF was positively associated.
      Objective work stress was associated (P = 0.003) with subjective burnout
      symptoms. CONCLUSIONS: PA, CRF, and body composition are associated with HRV
      based stress and recovery levels, which needs to be taken into account in the
      measurement, prevention, and treatment of work-related stress. The HRV-based
      method used to determine work-related stress and recovery was associated with
      self-reported burnout symptoms, but more research on the clinical importance of
      the methodology is needed.

PMID- 24742267
TI  - Heterogeneously substituted radicals and carbenes: photoelectron imaging of the
      FC(H)CN(-) and FCCN(-) anions.
AB  - This work represents the next step in the studies of heterogeneous substitution
      effects in cyanohalo radicals and carbenes. Negative-ion photoelectron imaging
      was used to investigate the substituted radical and carbene derivatives of
      fluoroacetonitrile. We report a closed-shell singlet ground state for
      cyanofluorocarbene, FCCN, with a directly measured adiabatic electron affinity EA
      = 2.081 +/- 0.002 eV and a singlet-triplet gap of DeltaE(S-T) = 0.42 +/- 0.04 eV,
      estimated through a combination of experimental and theoretical results. The open
      shell singlet (1)A" state was also observed experimentally. The cyanofluoromethyl
      radical, FC(H)CN, was similarly estimated to have an EA of 1.53 +/- 0.08 eV. This
      value was used to estimate the C-H bond dissociation energy (BDE) of
      fluoroacetonitrile, DH298 = 90.7 +/- 2.8 kcal mol(-1). The results are discussed
      in comparison with results for other fluoro- and cyano-substituted radicals and
      carbenes, and in light of our recent work on the radical and carbene derivatives
      of chloroacetonitrile. The estimated DeltaE(S-T) of FCCN agrees well with the
      general trend of similar carbenes. We also find that, similar to
      chloroacetonitrile, the low C-H BDE of fluoroaceotnitrile indicates a synergistic
      stabilization of the corresponding radical by a pi donor (halogen) and pi
      acceptor (CN).

PMID- 24742266
TI  - Venue-based recruitment of women at elevated risk for HIV: an HIV Prevention
      Trials Network study.
AB  - BACKGROUND: The challenge of identifying and recruiting U.S. women at elevated
      risk for HIV acquisition impedes prevention studies and services. HIV Prevention
      Trials Network (HPTN) 064 was a U.S. multisite, longitudinal cohort study
      designed to estimate HIV incidence among women living in communities with
      prevalent HIV and poverty. Venue-based sampling (VBS) methodologies and
      participant and venue characteristics are described. METHODS: Eligible women were
      recruited from 10 U.S. communities with prevalent HIV and poverty using VBS.
      Participant eligibility criteria included age 18-44 years, residing in a
      designated census tract/zip code, and self-report of at least one high-risk
      personal and/or male sexual partner characteristic associated with HIV
      acquisition (e.g., incarceration history). Ethnography was conducted to finalize
      recruitment areas and venues. RESULTS: Eight thousand twenty-nine women were
      screened and 2,099 women were enrolled (88% black, median age 29 years) over 14
      months. The majority of participants were recruited from outdoor venues (58%),
      retail spaces (18%), and social service organizations (13%). The proportion of
      women recruited per venue category varied by site. Most participants (73%) had
      both individual and partner characteristics that qualified them for the study;
      14% were eligible based on partner risk only. CONCLUSION: VBS is a feasible and
      effective approach to rapidly recruit a population of women at enhanced risk for
      HIV in the United States. Such a recruitment approach is needed in order to
      engage women most at risk and requires strong community engagement.

PMID- 24742269
TI  - Stibasilene Sb?Si and its lighter homologues: a comparative study.
AB  - The multiply bonded derivatives of the heavier main group elements are among the
      most challenging targets for synthetic pursuits. Those of them featuring a double
      bond between the silicon and group 15 element are represented mostly by the
      silaimines -N?Si< and phosphasilenes -P?Si< with a very few examples of
      arsasilenes -As?Si<. In this contribution, we report on the synthesis and
      structural elucidation of the first stable stibasilene and novel phosphasilene
      and arsasilene derivatives, featuring an identical substitution pattern. A
      systematic comparison within the series phosphasilene-arsasilene-stibasilene is
      made on the basis of their experimental and computational studies. 

PMID- 24742268
TI  - Feasibility of intensity-modulated and image-guided radiotherapy for locally
      advanced esophageal cancer.
AB  - BACKGROUND: In this study the feasibility of intensity-modulated radiotherapy
      (IMRT) and tomotherapy-based image-guided radiotherapy (IGRT) for locally
      advanced esophageal cancer was assessed. METHODS: A retrospective study of ten
      patients with locally advanced esophageal cancer who underwent concurrent
      chemotherapy with IMRT (1) and IGRT (9) was conducted. The gross tumor volume was
      treated to a median dose of 70 Gy (62.4-75 Gy). RESULTS: At a median follow-up of
      14 months (1-39 months), three patients developed local failures, six patients
      developed distant metastases, and complications occurred in two patients (1
      tracheoesophageal fistula, 1 esophageal stricture requiring repeated
      dilatations). No patients developed grade 3-4 pneumonitis or cardiac
      complications. CONCLUSIONS: IMRT and IGRT may be effective for the treatment of
      locally advanced esophageal cancer with acceptable complications.

PMID- 24742270
TI  - The determinants of poor respiratory health status in adults living with human
      immunodeficiency virus infection.
AB  - The increased longevity afforded by combination antiretroviral therapy in
      developed countries has led to an increased concern regarding senescence-related
      diseases in patients with human immunodeficiency virus (HIV) infection. Previous
      epidemiologic analyses have demonstrated an increased risk of chronic obstructive
      pulmonary disease, as well as a significant burden of respiratory symptoms in HIV
      infected patients. We performed the St. George's Respiratory Questionnaire (SGRQ)
      in 199 HIV-positive men, and determined the predominant factors contributing to
      poor respiratory-related health status. In univariate analyses, worse SGRQ scores
      were associated with respiratory-related variables such as greater smoking pack
      year history (p=0.028), lower forced expiratory volume in 1 second (FEV1)
      (p<0.001), and worse emphysema severity as quantified by computed tomographic
      imaging (p=0.017). In addition, HIV-specific variables, such as a history of
      plasma viral load >100,000 copies/mL (p=0.043), lower nadir CD4 cell count
      (p=0.040), and current CD4 cell count <=350 cells/MUL (p=0.005), as well as
      elevated levels of inflammatory markers, specifically plasma interleukin (IL)-6
      (p=0.002) and alpha-1 antitrypsin (p=0.005) were also associated with worse SGRQ
      scores. In a multiple regression model, FEV1, current CD4 count <=350 cells/MUL,
      and IL-6 levels remained significant contributors to reduced respiratory-related
      health status. HIV disease activity as measured by HIV-related immunosuppression
      in conjunction with the triggering of key inflammatory pathways may be important
      determinants of worse respiratory health status among HIV-infected individuals.
      Limitations of this analysis include the absence of available echocardiograms,
      diffusion capacity and lung volume testing, and an all-male cohort due to the
      demographics of the clinic population.

PMID- 24742271
TI  - Inhibitory effect of kaolin minerals compound against hepatitis C virus in Huh-7
      cell lines.
AB  - BACKGROUND: Hepatitis C virus (HCV) is estimated to infect 200 million
      individuals in the globe, including approximately 10 million in Pakistan causing
      both acute and chronic hepatitis. The standard treatment against HCV is pegylated
      interferon therapy in combination with a nucleoside analogue ribavirin. In
      addition, several herbal extracts and phytochemicals derivatives are used
      traditionally in the treatment of liver diseases as well as HCV infection. The
      present study determines the inhibitory effect of kaolin minerals compound
      against hepatitis C virus in Huh-7 cell lines. METHODS: Huh-7 cell lines were
      used for the in vitro HCV replication by using HCV positive sera from different
      patients with known HCV genotypes and viral titer/load. Total RNA was extracted
      from these infected cells and was quantified by real-time polymerase chain
      reaction (Real-time PCR). The viral titer was compared with the control samples
      to determine the anti-HCV activity of kaolin derived compounds. Kaolin is a group
      of clay minerals, with the chemical composition Al2 Si2O5 (OH)4. RESULTS: The
      results showed promising effectiveness of local kaolin derived anti-HCV compounds
      by causing 28% to 77% decrease in the HCV titer, when applied to infected Huh-7
      cell lines. This study provides the basis for future work on these compounds
      especially to determine the specific pathway and mechanism for inhibitory action
      in the replicon systems of viral hepatitis. CONCLUSIONS: Kaolin mineral
      derivatives show promising inhibitory effects against HCV genotypes 3a and 1a
      infection, which suggests its possible use as complementary and alternative
      medicine for HCV viral infection.

PMID- 24742272
TI  - Pulmonary delivery of docosahexaenoic acid mitigates bleomycin-induced pulmonary
      fibrosis.
AB  - BACKGROUND: Pulmonary fibrosis is an untreatable, fatal disease characterized by
      excess deposition of extracellular matrix and inflammation. Although the etiology
      of pulmonary fibrosis is unknown, recent studies have implicated dysregulated
      immune responses and wound healing. Since n-3 polyunsaturated fatty acids (n-3
      PUFAs) may beneficially modulate immune responses in a variety of inflammatory
      disorders, we investigated the therapeutic role of docosahexaenoic acid (DHA), a
      single n-3 PUFA, in lung fibrosis. METHODS: Intratracheal DHA or PBS was
      administered to mouse lungs 4 days prior to intratracheal bleomycin treatment.
      Body weight and survival were monitored for 21 days. Bronchoalveolar fluid (BALF)
      and lung inflammatory cells, cytokines, eicosanoids, histology and lung function
      were determined on serial days (0, 3, 7, 14, 21) after bleomycin injury. RESULTS:
      Intratracheal administration of DHA mitigated bleomycin-induced lung injury. Mice
      pretreated with DHA had significantly less weight loss and mortality after
      bleomycin injury. The lungs from DHA-pretreated mice had markedly less fibrosis.
      DHA pretreatment also protected the mice from the functional changes associated
      with bleomycin injury. Bleomycin-induced cellular inflammation in BALF and lung
      tissue was blunted by DHA pretreatment. These advantageous effects of DHA
      pretreatment were associated with decreased IL-6, LTB4, PGE2 and increased IL-10.
      CONCLUSIONS: Our findings demonstrate that intratracheal administration of DHA, a
      single PUFA, protected mice from the development of bleomycin-induced pulmonary
      inflammation and fibrosis. These results suggest that further investigations
      regarding the role of n-3 polyunsaturated fatty acids in fibrotic lung injury and
      repair are needed.

PMID- 24742273
TI  - Expression of endoglucanases in Pichia pastoris under control of the GAP
      promoter.
AB  - BACKGROUND: Plant-derived biomass is a potential alternative to fossil feedstocks
      for a greener economy. Enzymatic saccharification of biomass has been studied
      extensively and endoglucanases have been found to be a prerequisite for quick
      initial liquefaction of biomass under industrial conditions. Pichia pastoris,
      widely used for heterologous protein expression, can be utilized for fungal
      endoglucanase production. The recently marketed PichiaPinkTM expression system
      allows for rapid clone selection, and employs the methanol inducible AOX1
      promoter to ensure high protein expression levels. However, methanol is toxic and
      poses a fire hazard, issues which become more significant at an industrial scale.
      It is possible to eliminate these risks and still maintain high productivity by
      switching to the constitutive GAP promoter. RESULTS: In the present study, a
      plasmid carrying the constitutive GAP promoter was created for PichiaPinkTM. We
      then studied expression of two endoglucanases, AfCel12A from Aspergillus
      fumigatus and TaCel5A from Thermoascus aurantiacus, regulated by either the AOX1
      promoter or the GAP promoter. Initial experiments in tubes and small bioreactors
      showed that the levels of AfCel12A obtained with the constitutive promoter were
      similar or higher, compared to the AOX1 promoter, whereas the levels of TaCel5A
      were somewhat lower. After optimization of cultivation conditions using a 15-l
      bioreactor, the recombinant P. pastoris strains utilizing the GAP promoter
      produced ca. 3-5 g/l of total secreted protein, with CMCase activity equivalent
      to 1200 nkat/ml AfCel12A and 170 nkat/ml TaCel5A. CONCLUSIONS: We present a
      strategy for constitutive recombinant protein expression in the novel
      PichiaPinkTM system. Both AfCel12A and TaCel5A were successfully expressed
      constitutively in P. pastoris under the GAP promoter. Reasonable protein levels
      were reached after optimizing cultivation conditions.

PMID- 24742274
TI  - A descriptive study on evaluation of bio-medical waste management in a tertiary
      care public hospital of North India.
AB  - BACKGROUND: Proper management of Biomedical waste (BMW) generated in a healthcare
      facility is one of the most important functions of a healthcare worker (HCW) as
      its improper management not only poses risk to human beings and environment, but
      may also invite legal action against HCW as well as hospital administration. This
      study was carried out to evaluate quality of BMW management in 1100-bedded
      hospital attached to a tertiary care public institute in North India. METHODS: A
      checklist, including 29 parameters related to various functions to be carried out
      at source of generation by a HCW for BMW management was prepared by researcher
      and used after validation to record observations in all the 70 areas of hospital.
      A total of 6 visits were made to each area and mean percentage score was
      calculated for each area and each category of waste management. RESULTS: It was
      found that summated mean percentage score of 'Treatment Room of Wards', which
      were used exclusively by resident doctors, was significantly lower than Operation
      Theatres (p value: 0.033) and 'Central Waste Collection Points of Wards' (p
      value: 0.018) for the function of 'mutilation of recyclable waste' and it was
      significantly lower than all other areas (p value: 0.006 to 0.017) for the
      function of 'disinfection of waste'. CONCLUSION: It is concluded that more
      emphasis needs to be laid on 'mutilation of recyclable waste' and disinfection of
      waste' by HCWs especially resident doctors.

PMID- 24742276
TI  - Photophysics and photochemistry of a DNA-protein cross-linking model: a
      synergistic approach combining experiments and theory.
AB  - The photophysical and photochemical properties of 5-benzyluracil and 5,6
      benzyluracil, the latter produced by photocyclization of the former through
      irradiation with femtosecond UV laser pulses, are investigated both
      experimentally and theoretically. The absorption spectra of the two molecules are
      compared, and the principal electronic transitions involved are discussed, with
      particular emphasis on the perturbation induced on the two chromophore species
      (uracil and benzene) by their proximity. The photoproduct formation for different
      irradiation times was verified with high-performance liquid chromatography and
      nuclear magnetic resonance measurements. The steady-state fluorescence
      demonstrates that the fluorescence is a distinctive physical observable for
      detection and selective identification of 5- and 5,6-benzyluracil. The principal
      electronic decay paths of the two molecules, obtained through TDDFT calculations,
      explain the features observed in the emission spectra and the photoreactivity of
      5-benzyluracil. The order of magnitude of the lifetime of the excited states is
      derived with steady-state fluorescence anisotropy measurements and rationalized
      with the help of the computational findings. Finally, the spectroscopic data
      collected are used to derive the photocyclization and fluorescence quantum
      yields. In obtaining a global picture of the photophysical and photochemical
      properties of the two molecules, our findings demonstrates that the use of 5
      benzyluracil as a model system to study the proximity relations of a DNA base
      with a close-lying aromatic amino acid is valid at a local level since the main
      characteristics of the decay processes from the excited states of the
      uracil/thymine molecules remain almost unchanged in 5-benzyluracil, the main
      perturbation arising from the presence of the close-lying aromatic group. 

PMID- 24742275
TI  - Diffusion tensor imaging for outcome prediction in mild traumatic brain injury: a
      TRACK-TBI study.
AB  - We evaluated 3T diffusion tensor imaging (DTI) for white matter injury in 76
      adult mild traumatic brain injury (mTBI) patients at the semiacute stage (11.2+/
      3.3 days), employing both whole-brain voxel-wise and region-of-interest (ROI)
      approaches. The subgroup of 32 patients with any traumatic intracranial lesion on
      either day-of-injury computed tomography (CT) or semiacute magnetic resonance
      imaging (MRI) demonstrated reduced fractional anisotropy (FA) in numerous white
      matter tracts, compared to 50 control subjects. In contrast, 44 CT/MRI-negative
      mTBI patients demonstrated no significant difference in any DTI parameter,
      compared to controls. To determine the clinical relevance of DTI, we evaluated
      correlations between 3- and 6-month outcome and imaging,
      demographic/socioeconomic, and clinical predictors. Statistically significant
      univariable predictors of 3-month Glasgow Outcome Scale-Extended (GOS-E) included
      MRI evidence for contusion (odds ratio [OR] 4.9 per unit decrease in GOS-E;
      p=0.01), >=1 ROI with severely reduced FA (OR, 3.9; p=0.005), neuropsychiatric
      history (OR, 3.3; p=0.02), age (OR, 1.07/year; p=0.002), and years of education
      (OR, 0.79/year; p=0.01). Significant predictors of 6-month GOS-E included >=1 ROI
      with severely reduced FA (OR, 2.7; p=0.048), neuropsychiatric history (OR, 3.7;
      p=0.01), and years of education (OR, 0.82/year; p=0.03). For the subset of 37
      patients lacking neuropsychiatric and substance abuse history, MRI surpassed all
      other predictors for both 3- and 6-month outcome prediction. This is the first
      study to compare DTI in individual mTBI patients to conventional imaging,
      clinical, and demographic/socioeconomic characteristics for outcome prediction.
      DTI demonstrated utility in an inclusive group of patients with heterogeneous
      backgrounds, as well as in a subset of patients without neuropsychiatric or
      substance abuse history.

PMID- 24742277
TI  - Teriflunomide: a novel oral treatment for relapsing multiple sclerosis.
AB  - INTRODUCTION: Multiple sclerosis is a disabling chronic inflammatory disease of
      the CNS. New emerging oral treatments can offer efficacy with higher levels of
      therapeutic adherence. Teriflunomide is one such oral agent that has recently
      been approved for the treatment of relapsing multiple sclerosis (RMS). AREAS
      COVERED: The aim of this review is to describe the pharmacological profile of
      teriflunomide and review the vast clinical development program that paved the way
      for its approval, with emphasis on its safety and tolerability. EXPERT OPINION:
      Teriflunomide is a safe new oral medication for treating RMS. It is effective at
      reducing relapses, MRI activity and slowing disability progression. It is well
      tolerated, with mild and transitory side effects. Although teriflunomide is given
      a pregnancy category 'X' by the FDA and an effective contraception is needed, to
      date, there has been no evidence of teratogenicity in humans and a rapid washout
      procedure can lead to a virtually complete elimination. Its effectiveness
      appeared to be at least comparable to that of high-dose IFN-beta-1a, and although
      direct comparisons with other orals are still lacking, its tolerability and
      encouraging safety data suggest that teriflunomide could be considered an ideal
      first-line medication for RMS.

PMID- 24742278
TI  - Impact of smoking on dendritic cell phenotypes in the airway lumen of patients
      with COPD.
AB  - BACKGROUND: Myeloid dendritic cells (DCs) are increased in the airway wall of
      patients with chronic obstructive pulmonary disease (COPD), and postulated to
      play a crucial role in COPD. However, DC phenotypes in COPD are poorly
      understood. METHODS: Function-associated surface molecules on bronchoalveolar
      lavage fluid (BALF) DCs were analyzed using flow cytometry in current smokers
      with COPD, in former smokers with COPD and in never-smoking controls. RESULTS:
      Myeloid DCs of current smokers with COPD displayed a significantly increased
      expression of receptors for antigen recognition such as BDCA-1 or Langerin, as
      compared with never-smoking controls. In contrast, former smokers with COPD
      displayed a significantly decreased expression of these receptors, as compared
      with never-smoking controls. A significantly reduced expression of the maturation
      marker CD83 on myeloid DCs was found in current smokers with COPD, but not in
      former smokers with COPD. The chemokine receptor CCR5 on myeloid DCs, which is
      also important for the uptake and procession of microbial antigens, was strongly
      reduced in all patients with COPD, independently of the smoking status.
      CONCLUSION: COPD is characterized by a strongly reduced CCR5 expression on
      myeloid DCs in the airway lumen, which might hamper DC interactions with
      microbial antigens. Further studies are needed to better understand the role of
      CCR5 in the pathophysiology and microbiology of COPD.

PMID- 24742280
TI  - Surface molecular tailoring using pH-switchable supramolecular dendron-ligand
      assemblies.
AB  - The rational design of materials with tailored properties is of paramount
      importance for a wide variety of biological, medical, electronic and optical
      applications. Here we report molecular level control over the spatial
      distribution of functional groups on surfaces utilizing self-assembled monolayers
      (SAMs) of pH-switchable surface-appended pseudorotaxanes. The supramolecular
      systems were constructed from a poly(aryl ether) dendron-containing a
      dibenzo[24]crown-8 (DB24C8) macrocycle and a thiol ligand-containing a
      dibenzylammonium recognition site and a fluorine end group. The dendron
      establishes the space (dendritic effect) that each pseudorotaxane occupies on the
      SAM. Following SAM formation, the dendron is released from the surface by
      switching off the noncovalent interactions upon pH stimulation, generating
      surface materials with tailored physical and chemical properties. 

PMID- 24742279
TI  - Reprogramming of the chick retinal pigmented epithelium after retinal injury.
AB  - BACKGROUND: One of the promises in regenerative medicine is to regenerate or
      replace damaged tissues. The embryonic chick can regenerate its retina by
      transdifferentiation of the retinal pigmented epithelium (RPE) and by activation
      of stem/progenitor cells present in the ciliary margin. These two ways of
      regeneration occur concomitantly when an external source of fibroblast growth
      factor 2 (FGF2) is present after injury (retinectomy). During the process of
      transdifferentiation, the RPE loses its pigmentation and is reprogrammed to
      become neuroepithelium, which differentiates to reconstitute the different cell
      types of the neural retina. Somatic mammalian cells can be reprogrammed to become
      induced pluripotent stem cells by ectopic expression of pluripotency-inducing
      factors such as Oct4, Sox2, Klf4, c-Myc and in some cases Nanog and Lin-28.
      However, there is limited information concerning the expression of these factors
      during natural regenerative processes. Organisms that are able to regenerate
      their organs could share similar mechanisms and factors with the reprogramming
      process of somatic cells. Herein, we investigate the expression of pluripotency
      inducing factors in the RPE after retinectomy (injury) and during
      transdifferentiation in the presence of FGF2. RESULTS: We present evidence that
      upon injury, the quiescent (p27(Kip1)+/BrdU-) RPE cells transiently
      dedifferentiate and express sox2, c-myc and klf4 along with eye field
      transcriptional factors and display a differential up-regulation of alternative
      splice variants of pax6. However, this transient process of dedifferentiation is
      not sustained unless FGF2 is present. We have identified lin-28 as a downstream
      target of FGF2 during the process of retina regeneration. Moreover, we show that
      overexpression of lin-28 after retinectomy was sufficient to induce
      transdifferentiation of the RPE in the absence of FGF2. CONCLUSION: These
      findings delineate in detail the molecular changes that take place in the RPE
      during the process of transdifferentiation in the embryonic chick, and
      specifically identify Lin-28 as an important factor in this process. We propose a
      novel model in which injury signals initiate RPE dedifferentiation, while FGF2 up
      regulates Lin-28, allowing for RPE transdifferentiation to proceed.

PMID- 24742281
TI  - VO2 nanowires assembled into hollow microspheres for high-rate and long-life
      lithium batteries.
AB  - Development of three-dimensional nanostructures with high surface area and
      excellent structural stability is an important approach for realizing high-rate
      and long-life battery electrodes. Here, we report VO2 hollow microspheres showing
      empty spherical core with radially protruding nanowires, synthesized through a
      facile and controllable ion-modulating approach. In addition, by controlling the
      self-assembly of negatively charged C12H25SO4(-) spherical micelles and
      positively charged VO(2+) ions, six-armed microspindles and random nanowires are
      also prepared. Compared with them, VO2 hollow microspheres show better
      electrochemical performance. At high current density of 2 A/g, VO2 hollow
      microspheres exhibit 3 times higher capacity than that of random nanowires, and
      80% of the original capacity is retained after 1000 cycles. The superior
      performance of VO2 hollow microspheres is because they exhibit high surface area
      about twice higher than that of random nanowires and also provide an efficient
      self-expansion and self-shrinkage buffering during lithiation/delithiation, which
      effectively inhibits the self-aggregation of nanowires. This research indicates
      that VO2 hollow microspheres have great potential for high-rate and long-life
      lithium batteries. 

PMID- 24742282
TI  - RNA sequencing-mediated transcriptome analysis of rice plants in endoplasmic
      reticulum stress conditions.
AB  - BACKGROUND: The endoplasmic reticulum (ER) stress response is widely known to
      function in eukaryotes to maintain the homeostasis of the ER when unfolded or
      misfolded proteins are overloaded in the ER. To understand the molecular
      mechanisms of the ER stress response in rice (Oryza sativa L.), we previously
      analyzed the expression profile of stably transformed rice in which an ER stress
      sensor/transducer OsIRE1 was knocked-down, using the combination of preliminary
      microarray and quantitative RT-PCR. In this study, to obtain more detailed
      expression profiles of genes involved in the initial stages of the ER stress
      response in rice, we performed RNA sequencing of wild-type and transgenic rice
      plants produced by homologous recombination in which endogenous genomic OsIRE1
      was replaced by missense alleles defective in ribonuclease activity. RESULTS: At
      least 38,076 transcripts were investigated by RNA sequencing, 380 of which
      responded to ER stress at a statistically significant level (195 were upregulated
      and 185 were downregulated). Furthermore, we successfully identified 17 genes
      from the set of 380 ER stress-responsive genes that were not included in the
      probe set of the currently available microarray chip in rice. Notably, three of
      these 17 genes were non-annotated genes, even in the latest version of the Rice
      Annotation Project Data Base (RAP-DB, version IRGSP-1.0). CONCLUSIONS: Therefore,
      RNA sequencing-mediated expression profiling provided valuable information about
      the ER stress response in rice plants and led to the discovery of new genes
      related to ER stress.

PMID- 24742283
TI  - Human donor milk for the vulnerable infant: a Canadian perspective.
AB  - Breast milk is the normal way to feed infants and is accepted worldwide as the
      optimal first source of nutrition. Though the majority intend to breastfeed, many
      mothers of sick, hospitalized newborns, particularly those of very low birth
      weight, are unable to provide a full volume of milk due to numerous physical and
      emotional barriers to breastfeeding. This vulnerable population of infants may
      benefit most from receiving breast milk nutrition and thus pasteurized donor milk
      should be the first consideration for supplementation when there is an inadequate
      supply of mother's own milk. This commentary will briefly review the history of
      milk banking in Canada, as well as the best available evidence for donor milk use
      in the very low birth weight population, including available economic analyses,
      with a view to advocate for its use in these vulnerable infants. 

PMID- 24742284
TI  - Longitudinal Associations Between Reactive and Regulatory Temperament Traits and
      Depressive Symptoms in Middle Childhood.
AB  - Although a large literature has examined the role of temperament in adult and
      adolescent depression, few studies have investigated interactions between
      reactive and regulatory temperament traits in shaping depressive symptoms in
      children over time. Child temperament measures (laboratory observations and
      maternal reports) and depressive symptoms were collected from 205 seven-year-olds
      (46% boys), who were followed up 1 (N=181) and 2 (N=171) years later. Child
      participants were Caucasian (87.80%), Asian (1.95%), or other ethnicity (7.80%);
      2.45% of the sample was missing ethnicity data. Multilevel modeling was used to
      investigate within- and between-person variance in intercepts and slopes of child
      depressive symptoms. A steeper increase in depressive symptoms was found for
      children lower in laboratory-assessed effortful control (EC). Lower mother
      reported surgency and higher mother-reported NE predicted increases in child
      depressive symptoms in the context of lower mother-reported EC. Our findings
      implicate EC as having main and moderating effects related to depressive symptoms
      in middle childhood. We emphasize the importance of developing prevention
      programs that enhance EC-like abilities.

PMID- 24742285
TI  - Immobilized bisdiazaphospholane catalysts for asymmetric hydroformylation.
AB  - Condensation reactions of enantiopure bis-3,4-diazaphospholanes (BDPs) that are
      functionalized with carboxylic acids enable covalent attachment to bead and
      silica supports. Exposure of tethered BDPs to the hydroformylation catalyst
      precursor, Rh(acac)(CO)2, yields catalysts for immobilized asymmetric
      hydroformylation (iAHF) of prochiral alkenes. Compared with homogeneous
      catalysts, catalysts immobilized on Tentagel resins exhibit similarly high
      regioselectivity and enantioselectivity. When corrected for apparent catalyst
      loading, the activity of the immobilized catalysts approaches that of the
      homogeneous analogues. Excellent recyclability with trace levels of rhodium
      leaching are observed in batch and flow reactor conditions. Silica-bound
      catalysts exhibit poorer enantioselectivities. 

PMID- 24742287
TI  - Information-seeking in cancer survivors: application of the Comprehensive Model
      of Information Seeking to HINTS 2007 data.
AB  - Despite health care providers' best efforts, many cancer survivors have unmet
      informational and support needs. As a result, cancer survivors often have to meet
      these needs themselves, and how they approach this process is poorly understood.
      The authors aimed to validate and extend the Comprehensive Model of Information
      Seeking to examine information-seeking behaviors across a variety of channels of
      information delivery and to explore the impact of health-related factors on
      levels of information seeking. The data of 459 cancer survivors were drawn from
      the National Cancer Institute's 2007 Health Information National Trends Survey.
      Structural equation modeling was used to evaluate the associations among health
      related factors, information-carrier factors, and information-seeking behavior.
      Results confirmed direct effects of direct experience, salience, and information
      carrier characteristics on information-carrier utility. However, the direct
      impact of demographics and beliefs on information-carrier utility was not
      confirmed, nor were the effects of information-carrier factors on information
      seeking behavior. Contrary to expectations, salience had direct effect on
      information-seeking behavior and on information-carrier characteristics. These
      results show that understanding antecedents of information seeking will inform
      the development and implementation of systems of care that will help providers
      better meet cancer survivors' needs. 

PMID- 24742286
TI  - Activation of Akt1 accelerates carcinogen-induced tumorigenesis in mammary gland
      of virgin and post-lactating transgenic mice.
AB  - BACKGROUND: Data from in vivo and in vitro studies suggest that activation of Akt
      regulates cell survival signaling and plays a key role in tumorigenesis. Hence,
      transgenic mice were created to explore the oncogenic role of Akt1 in the
      development of mammary tumors. METHODS: The transgenic mice were generated by
      expressing myristoylated-Akt1 (myr-Akt1) under the control of the MMTV-LTR
      promoter. The carcinogen 7, 12 dimethyl-1,2-benzanthracene (DMBA) was used to
      induce tumor formation. RESULTS: The MMTV driven myr-Akt1 transgene expression
      was detected primarily in the mammary glands, uterus, and ovaries. The expression
      level increased significantly in lactating mice, suggesting that the response was
      hormone dependent. The total Akt expression level in the mammary gland was also
      higher in the lactating mice. Interestingly, the expression of MMTVmyr-Akt1 in
      the ovaries of the transgenic mice caused significant increase in circulating
      estrogen levels, even at the post-lactation stage. Expression of myr-Akt1 in
      mammary glands alone did not increase the frequency of tumor formation. However,
      there was an increased susceptibility of forming mammary tumors induced by DMBA
      in the transgenic mice, especially in mice post-lactation. Within 34 weeks, DMBA
      induced mammary tumors in 42.9% of transgenic mice post-lactation, but not in
      wild-type mice post-lactation. The myr-Akt1 mammary tumors induced by DMBA had
      increased phosphorylated-Akt1 and showed strong expression of estrogen receptor
      (ERalpha) and epidermal growth factor receptor (EGFR). In addition, Cyclin D1 was
      more frequently up-regulated in mammary tumors from transgenic mice compared to
      tumors from wild-type mice. Overexpression of Cyclin D1, however, was not
      completely dependent on activated Akt1. Interestingly, mammary tumors that had
      metastasized to secondary sites had increased expression of Twist and Slug, but
      low expression of Cyclin D1. CONCLUSIONS: In summary, the MMTVmyr-Akt1 transgenic
      mouse model could be useful to study mechanisms of ER-positive breast tumor
      development.

PMID- 24742288
TI  - Interstitial 11q deletion: genomic characterization and neuropsychiatric follow
      up from early infancy to adolescence and literature review.
AB  - BACKGROUND: Interstitial deletions of chromosome 11 long arm are rarely observed
      and the associated phenotype ranges from normal to severe, depending on the
      position and size of the deletion and on the presence of unmasked recessive genes
      on the normal homologous. To our knowledge 32 cases are reported in literature
      with three family cases. Phenotype-genotype correlation is not very clear and the
      most common features are characteristic facial dysmorphisms, palate anomalies and
      developmental delay. Growth retardation is not typical and other major
      malformations are reported in some cases. CASE PRESENTATION: We described a child
      with 11q interstitial deletion diagnosed at birth with hypotonia and minor
      dysmorphisms using standard cytogenetic techniques; array CGH was subsequently
      performed to define the deletion at a molecular level. CONCLUSIONS: This case
      gave us the opportunity to attempt a genotype-phenotype correlation reviewing the
      literature and to describe a rehabilitative program that improved the development
      perspectives of this child.

PMID- 24742289
TI  - Navigating wastewater energy recovery strategies: a life cycle comparison of
      anaerobic membrane bioreactor and conventional treatment systems with anaerobic
      digestion.
AB  - The objective of this study was to evaluate emerging anaerobic membrane
      bioreactor (AnMBR) technology in comparison with conventional wastewater energy
      recovery technologies. Wastewater treatment process modeling and systems analyses
      were combined to evaluate the conditions under which AnMBR may produce more net
      energy and have lower life cycle environmental emissions than high rate activated
      sludge with anaerobic digestion (HRAS+AD), conventional activated sludge with
      anaerobic digestion (CAS+AD), and an aerobic membrane bioreactor with anaerobic
      digestion (AeMBR+AD). For medium strength domestic wastewater treatment under
      baseline assumptions at 15  degrees C, AnMBR recovered 49% more energy as biogas
      than HRAS+AD, the most energy positive conventional technology considered, but
      had significantly higher energy demands and environmental emissions. Global
      warming impacts associated with AnMBR were largely due to emissions of effluent
      dissolved methane. For high strength domestic wastewater treatment, AnMBR
      recovered 15% more net energy than HRAS+AD, and the environmental emissions gap
      between the two systems was reduced. Future developments of AnMBR technology in
      low energy fouling control, increased flux, and management of effluent methane
      emissions would make AnMBR competitive with HRAS+AD. Rapid advancements in AnMBR
      technology must continue to achieve its full economic and environmental potential
      as an energy recovery strategy for domestic wastewater. 

PMID- 24742290
TI  - Dynamic inhomogeneity in the photodynamics of cyanobacterial phytochrome Cph1.
AB  - Phytochromes are widespread red/far-red photosensory proteins well known as
      critical regulators of photomorphogenesis in plants. It is often assumed that
      natural selection would have optimized the light sensing efficiency of
      phytochromes to minimize nonproductive photochemical deexcitation pathways.
      Surprisingly, the quantum efficiency for the forward Pr-to-Pfr photoconversion of
      phytochromes seldom exceeds 15%, a value very much lower than that of animal
      rhodopsins. Exploiting ultrafast excitation wavelength- and temperature-dependent
      transient absorption spectroscopy, we resolve multiple pathways within the
      ultrafast photodynamics of the N-terminal PAS-GAF-PHY photosensory core module of
      cyanobacterial phytochrome Cph1 (termed Cph1Delta) that are primarily responsible
      for the overall low quantum efficiency. This inhomogeneity primarily reflects a
      long-lived fluorescent subpopulation that exists in equilibrium with a spectrally
      distinct, photoactive subpopulation. The fluorescent subpopulation is favored at
      elevated temperatures, resulting in anomalous excited-state dynamics (slower
      kinetics at higher temperatures). The spectral and kinetic behavior of the
      fluorescent subpopulation strongly resembles that of the photochemically
      compromised and highly fluorescent Y176H variant of Cph1Delta. We present an
      integrated, heterogeneous model for Cph1Delta that is based on the observed
      transient and static spectroscopic signals. Understanding the molecular basis for
      this dynamic inhomogeneity holds potential for rational design of efficient
      phytochrome-based fluorescent and photoswitchable probes. 

PMID- 24742293
TI  - Catalytic oxidation of methanol to formaldehyde by mass-selected vanadium oxide
      clusters supported on a TiO2(110) surface.
AB  - We report the results of a systematic study of the catalytic activity of mass
      selected vanadium oxide clusters deposited on rutile TiO2 surfaces under
      ultrahigh vacuum (UHV) conditions. Our results show that supported V, VO, and VO2
      clusters are not catalytically active for the oxidative dehydrogenation of
      methanol to formaldehyde but can be made catalytically active by postoxidation.
      In addition, we found that the postoxidized VO/TiO2 produces the most
      formaldehyde. Scanning tunneling microscopy (STM) imaging of the postoxidized
      VO/TiO2 reveals isolated clusters with height and width indicative of VO3 bound
      to the TiO2 surface. Our results are consistent with previous density functional
      theory (DFT) calculations that predict that VO3 will be produced by postoxidation
      of VO and that VO3/TiO2 is an active catalyst. 

PMID- 24742291
TI  - The prevalence of glucose-6-phosphate dehydrogenase deficiency in Gambian school
      children.
AB  - BACKGROUND: Primaquine, the only available drug effective against Plasmodium
      falciparum sexual stages, induces also a dose-dependent haemolysis, especially in
      glucose-6-phosphate dehydrogenase deficient (G6PDd) individuals. Therefore, it is
      important to determine the prevalence of this deficiency in areas that would
      potentially benefit from its use. The prevalence of G6PD deficiency by genotype
      and enzyme activity was determined in healthy school children in The Gambia.
      METHODS: Blood samples from primary school children collected during a dry season
      malaria survey were screened for G6PDd and malaria infection. Genotypes for
      allele mutations reported in the country; 376, 202A-, 968A- and 542 were analysed
      while enzyme activity (phenotype) was assayed using a semi-quantitative
      commercial test kit. Enzyme activity values were fitted in a finite mixture model
      to determine the distribution and calculate a cut-off for deficiency. The
      association between genotype and phenotype for boys and girls as well as the
      association between mutant genotype and deficient phenotype was analysed.
      RESULTS: Samples from 1,437 children; 51% boys were analysed. The prevalence of
      P. falciparum malaria infection was 14%. The prevalence of the 202A-, 968 and 542
      mutations was 1.8%, 2.1% and 1.0%, respectively, and higher in boys than in
      girls. The prevalence of G6PDd phenotype was 6.4% (92/1,437), 7.8% (57/728) in
      boys and 4.9% (35/709) in girls with significantly higher odds in the former (OR
      1.64, 95% CI 1.05, 2.53, p = 0.026). The deficient phenotype was associated with
      reduced odds of malaria infection (OR 0.77, 95% CI 0.36, 1.62, p = 0.49).
      CONCLUSIONS: There is a weak association between genotype and phenotype estimates
      of G6PDd prevalence. The phenotype expression of deficiency represents
      combinations of mutant alleles rather than specific mutations. Genotype studies
      in individuals with a deficient phenotype would help identify alleles responsible
      for haemolysis.

PMID- 24742292
TI  - Effects of serotonergic medications on locomotor performance in humans with
      incomplete spinal cord injury.
AB  - Incomplete spinal cord injury (iSCI) often results in significant motor
      impairments that lead to decreased functional mobility. Loss of descending
      serotonergic (5HT) input to spinal circuits is thought to contribute to motor
      impairments, with enhanced motor function demonstrated through augmentation of
      5HT signaling. However, the presence of spastic motor behaviors in SCI is
      attributed, in part, to changes in spinal 5HT receptors that augment their
      activity in the absence of 5HT, although data demonstrating motor effects of 5HT
      agents that deactivate these receptors are conflicting. The effects of
      enhancement or depression of 5HT signaling on locomotor function have not been
      thoroughly evaluated in human iSCI. Therefore, the aim of the current study was
      to investigate acute effects of 5HT medications on locomotion in 10 subjects with
      chronic (>1 year) iSCI. Peak overground and treadmill locomotor performance,
      including measures of gait kinematics, electromyographic (EMG) activity, and
      oxygen consumption, were assessed before and after single-dose administration of
      either a selective serotonin reuptake inhibitor (SSRI) or a 5HT antagonist using
      a double-blinded, randomized, cross-over design. Results indicate that neither
      medication led to improvements in locomotion, with a significant decrease in peak
      overground gait speed observed after 5HT antagonists (from 0.8+/-0.1 to 0.7+/-0.1
      m/s; p=0.01). Additionally, 5-HT medications had differential effects on EMG
      activity, with 5HT antagonists decreasing extensor activity and SSRIs increasing
      flexor activity. Our data therefore suggest that acute manipulation of 5HT
      signaling, despite changes in muscle activity, does not improve locomotor
      performance after iSCI.

PMID- 24742294
TI  - The role of the TP73 gene and its transcripts in neuro-oncology.
AB  - Protein p73 is a member of the p53 protein family that can induce cell cycle
      arrest or apoptosis by the activation of p53-responsive genes as well as p53
      independent pathways. Alternative promoter usage, together with differential
      splicing of the C-terminal exons, forms several distinct mRNAs that are
      translated into corresponding protein isoforms containing different domains.
      While TAp73 isoforms respond to genotoxic stress in a manner similar to tumor
      suppressor p53, DeltaTAp73 isoforms inhibit apoptosis during normal development
      and in cancer cell lines. Thus, the impact of p73 on tumorigenesis depends on a
      subtle balance between tumor-promoting and -suppressing isoforms. Due to the
      structural homology between p53 and p73, a subtle balance among p53 family
      members and their isoforms could influence glioma cell evolution toward
      malignancy. Thus, the p73 status has to be considered when studying the
      regulatory role of p53 protein in gliomagenesis. The presented review summarizes
      recent knowledge about the issue of p73 and its isoforms with respect to neuro
      oncology research.

PMID- 24742295
TI  - Synthesis of reboxetine intermediate and carnitine acetyltransferase inhibitor
      via NBS-induced electrophilic multicomponent reaction.
AB  - N-Bromosuccinimide-induced electrophilic multicomponent reaction has been applied
      to the synthesis of Reboxetine intermediate, a highly potent selective
      norepinephrine reuptake inhibitor. By simply changing the olefinic partner, the
      synthesis of a carnitine acetyltransferase inhibitor, which contains a 2,6,6
      trisubstituted morpholine system, can be accomplished. 

PMID- 24742297
TI  - Large deviations for nonlocal stochastic neural fields.
AB  - We study the effect of additive noise on integro-differential neural field
      equations. In particular, we analyze an Amari-type model driven by a Q-Wiener
      process, and focus on noise-induced transitions and escape. We argue that proving
      a sharp Kramers' law for neural fields poses substantial difficulties, but that
      one may transfer techniques from stochastic partial differential equations to
      establish a large deviation principle (LDP). Then we demonstrate that an
      efficient finite-dimensional approximation of the stochastic neural field
      equation can be achieved using a Galerkin method and that the resulting finite
      dimensional rate function for the LDP can have a multiscale structure in certain
      cases. These results form the starting point for an efficient practical
      computation of the LDP. Our approach also provides the technical basis for
      further rigorous study of noise-induced transitions in neural fields based on
      Galerkin approximations.Mathematics Subject Classification (2000): 60F10, 60H15,
      65M60, 92C20. 

PMID- 24742296
TI  - A comprehensive study of small non-frameshift insertions/deletions in proteins
      and prediction of their phenotypic effects by a machine learning method (KD4i).
AB  - BACKGROUND: Small insertion and deletion polymorphisms (Indels) are the second
      most common mutations in the human genome, after Single Nucleotide Polymorphisms
      (SNPs). Recent studies have shown that they have significant influence on genetic
      variation by altering human traits and can cause multiple human diseases. In
      particular, many Indels that occur in protein coding regions are known to impact
      the structure or function of the protein. A major challenge is to predict the
      effects of these Indels and to distinguish between deleterious and neutral
      variants. When an Indel occurs within a coding region, it can be either
      frameshifting (FS) or non-frameshifting (NFS). FS-Indels either modify the
      complete C-terminal region of the protein or result in premature termination of
      translation. NFS-Indels insert/delete multiples of three nucleotides leading to
      the insertion/deletion of one or more amino acids. RESULTS: In order to study the
      relationships between NFS-Indels and Mendelian diseases, we characterized NFS
      Indels according to numerous structural, functional and evolutionary parameters.
      We then used these parameters to identify specific characteristics of disease
      causing and neutral NFS-Indels. Finally, we developed a new machine learning
      approach, KD4i, that can be used to predict the phenotypic effects of NFS-Indels.
      CONCLUSIONS: We demonstrate in a large-scale evaluation that the accuracy of KD4i
      is comparable to existing state-of-the-art methods. However, a major advantage of
      our approach is that we also provide the reasons for the predictions, in the form
      of a set of rules. The rules are interpretable by non-expert humans and they thus
      represent new knowledge about the relationships between the genotype and
      phenotypes of NFS-Indels and the causative molecular perturbations that result in
      the disease.

PMID- 24742298
TI  - Cellular and molecular immunological mechanisms in eosinophilic esophagitis: an
      updated overview of their clinical implications.
AB  - Eosinophilic esophagitis (EoE) is a pathophysiologically complex disorder driven
      by distinct, multiple mechanisms involving a large number of cells, molecules,
      and genes. Associated with food allergy from its initial descriptions, a key role
      for the Th2-type cytokines IL-5 and IL-13 in recruiting and activating
      eosinophils has been described. Epithelial cells have been recognized as major
      effectors in initiating EoE, both through their recruitment of iNKT cells towards
      the esophageal epithelium, which constitutes a major cytokine source, and through
      the release of eotaxin-3 and other chemoattractants. Epithelial and mesenchymal
      released TSLP is a key regulator for which a connecting role between the adaptive
      and innate mucosal-associated immune response has been suggested. Finally,
      activated eosinophil- and mast cell-derived TGF beta1 secretion is crucial in EoE
      associated tissue remodeling. 

PMID- 24742299
TI  - The centrality of laboratory services in the HIV treatment and prevention
      cascade: The need for effective linkages and referrals in resource-limited
      settings.
AB  - Strong laboratory services and systems are critical for delivering timely and
      quality health services that are vital to reduce patient attrition in the HIV
      treatment and prevention cascade. However, challenges exist in ensuring effective
      laboratory health systems strengthening and linkages. In particular, linkages and
      referrals between laboratory testing and other services need to be considered in
      the context of an integrated health system that includes prevention, treatment,
      and strategic information. Key components of laboratory health systems that are
      essential for effective linkages include an adequate workforce, appropriate point
      of-care (POC) technology, available financing, supply chain management systems,
      and quality systems improvement, including accreditation. In this review, we
      highlight weaknesses of and gaps between laboratory testing and other program
      services. We propose a model for strengthening these systems to ensure effective
      linkages of laboratory services for improved access and retention in care of
      HIV/AIDS patients, particularly in low- and middle-income countries.

PMID- 24742300
TI  - Guidance strategies for a participatory ergonomic intervention to increase the
      use of ergonomic measures of workers in construction companies: a study design of
      a randomised trial.
AB  - BACKGROUND: More than seven out of 10 Dutch construction workers describe their
      work as physically demanding. Ergonomic measures can be used to reduce these
      physically demanding work tasks. To increase the use of ergonomic measures,
      employers and workers have to get used to other working methods and to
      maintaining them. To facilitate this behavioural change, participatory ergonomics
      (PE) interventions could be useful. For this study a protocol of a PE
      intervention is adapted in such a way that the intervention can be performed by
      an ergonomics consultant through face-to-face contacts or email contacts. The
      objective of this study is to evaluate the effectiveness of the face-to-face
      guidance strategy and the e-guidance strategy on the primary outcome measure: use
      of ergonomic measures by individual construction workers, and on the secondary
      outcome measures: the work ability, physical functioning and limitations due to
      physical problems of individual workers. METHODS/DESIGN: The present study is a
      randomised intervention trial of six months in 12 companies to establish the
      effects of a PE intervention guided by four face-to-face contacts (N = 6) or
      guided by 13 email contacts (N = 6) on the primary and secondary outcome measures
      at baseline and after six months. Construction companies are randomly assigned to
      one of the guidance strategies with the help of a computer generated
      randomisation table. In addition, a process evaluation for both strategies will
      be performed to determine reach, dose delivered, dose received, precision,
      competence, satisfaction and behavioural change to find possible barriers and
      facilitators for both strategies. A cost-benefit analysis will be performed to
      establish the financial consequences of both strategies. The present study is in
      accordance with the CONSORT statement. DISCUSSION: The outcome of this study will
      help to 1) evaluate the effect of both guidance strategies, and 2) find barriers
      to and facilitators of both guidance strategies. When these strategies are
      effective, implementation within occupational health services can take place to
      guide construction companies (and others) with the implementation of ergonomic
      measures. TRIAL REGISTRATION: [corrected] Trailnumber: ISRCTN73075751, Date of
      registration: 30 July 2013.

PMID- 24742301
TI  - The impact of excess body weight at the hospital frontline.
AB  - Quantification of disease burden by deaths or years lived with disability is a
      useful indicator as it informs prevention by accounting for health loss but it
      does not reflect the needs for health services. An alternative indicator is to
      quantify the impact of a risk factor on health care utilization. In an article
      published in BMC Medicine, Reeves and colleagues describe the relationship
      between body mass index in 1.2 million women (England) and hospital admission
      rates. The main finding was that around one in eight hospital admissions was
      attributable to overweight or obesity, translating to around 420,000 extra
      hospital admissions, and two million extra days spent in hospital, annually.
      These findings reinforce the evidence that excess body weight is associated with
      extensive healthcare utilization and emphasize the need to scale-up and speed-up
      research if global problems, such as obesity, are to be tackled with due
      alacrity.Please see related research: http://www.biomedcentral.com/1741
      7015/12/45. 

PMID- 24742302
TI  - Cardioprotective activity of placental growth factor in a rat model of acute
      myocardial infarction: nanoparticle-based delivery versus direct myocardial
      injection.
AB  - BACKGROUND: To comparatively evaluate the cardioprotective activity of placental
      growth factor (PGF) delivered through direct injection and a nanoparticle-based
      system respectively and to study the underlying mechanisms in a rat model of
      acute myocardial infarction (AMI). METHODS: Poly lactic-co-glycolic acid (PLGA)
      based PGF-carrying nanoparticles (PGF-PLGANPs) were created. The mean size and
      morphology of particles were analyzed with particle size analyzer and
      transmission electronic microscopy (TEM). Encapsulation efficiency and sustained
      release dose curve were analyzed by ELISA. Sprague-Dawley rats were randomized
      into four groups (n = 10). While animals in the first group were left untreated
      as controls, those in the other 3 groups underwent surgical induction of AMI,
      followed by treatment with physiological saline, PGF, and PGF-PLGANPs,
      respectively. Cardiac function was evaluated by transthoracic echocardiography at
      4 weeks after treatment. At 6 weeks, rats were sacrificed, infarction size was
      analyzed with Masson trichrome staining, and protein contents of TIMP-2, MT1-MMP
      and MMP-2 at the infarction border were determined by immunohistochemistry and
      western blotting analysis. RESULTS: PGF was released for at least 15 days,
      showing successful preparation of PGF-PLGANPs. Coronary artery ligation
      successfully induced AMI. Compared to physiological saline control, PGF, injected
      to the myocardium either as a nude molecule or in a form of nanoparticles,
      significantly reduced infarction size, improved cardiac function, and elevated
      myocardial expression of TIMP-2, MT1-MMP, and MMP-2 (P < 0.05). The effect of PGF
      PLGANPs was more pronounced than that of non-encapsulated PGF (P < 0.05).
      CONCLUSION: Target PGF delivery to myocardium may improve cardiac function after
      AMI in rats. PLGA-based nanoparticles appear to be a better approach to delivery
      PGF. PGF exerts its cardioprotective effect at least partially through regulating
      metalloproteinase-mediated myocardial tissue remodeling.

PMID- 24742303
TI  - Proteomic comparison of 3D and 2D glioma models reveals increased HLA-E
      expression in 3D models is associated with resistance to NK cell-mediated
      cytotoxicity.
AB  - Three-dimensional cell culture techniques can better reflect the in vivo
      characteristics of tumor cells compared with traditional monolayer cultures.
      Compared with their 2D counterparts, 3D-cultured tumor cells showed enhanced
      resistance to the cytotoxic T cell-mediated immune response. However, it remains
      unclear whether 3D-cultured tumor cells have an enhanced resistance to NK cell
      cytotoxicity. In this study, a total of 363 differentially expressed proteins
      were identified between the 2D- and 3D-cultured U251 cells by comparative
      proteomics, and an immune-associated protein-protein interaction (PPI) network
      based on these differential proteins was constructed by bioinformatics. Within
      the network, HLA-E, as a molecule for inhibiting NK cell activation, was
      significantly up-regulated in the 3D-cultured tumor cells. Then, we found that
      the 3D-cultured U251 cells exhibited potent resistance to NK cell cytotoxicity in
      vitro and were prone to tumor formation in vivo. The resistance of the 3D
      cultured tumor cells to NK cell lysis was mediated by the HLA-E/NKG2A interaction
      because the administration of antibodies that block either HLA-E or NKG2A
      completely eliminated this resistance and significantly decreased tumor
      formation. Taken together, our findings indicate that HLA-E up-regulation in 3D
      cultured cells may result in enhanced tumor resistance to NK cell-mediated immune
      response. 

PMID- 24742304
TI  - Scalable production of highly sensitive nanosensors based on graphene
      functionalized with a designed G protein-coupled receptor.
AB  - We have developed a novel, all-electronic biosensor for opioids that consists of
      an engineered MU-opioid receptor protein, with high binding affinity for opioids,
      chemically bonded to a graphene field-effect transistor to read out ligand
      binding. A variant of the receptor protein that provided chemical recognition was
      computationally redesigned to enhance its solubility and stability in an aqueous
      environment. A shadow mask process was developed to fabricate arrays of hundreds
      of graphene transistors with average mobility of ~1500 cm(2) V(-1) s(-1) and
      yield exceeding 98%. The biosensor exhibits high sensitivity and selectivity for
      the target naltrexone, an opioid receptor antagonist, with a detection limit of
      10 pg/mL. 

PMID- 24742305
TI  - An efficient mono-component polymeric intumescent flame retardant for
      polypropylene: preparation and application.
AB  - We found in our previous study that ethylenediamine- or ethanolamine-modified
      ammonium polyphosphates could be used alone as an intumescent flame retardant for
      polypropylene (PP), but their flame-retardant efficiency was not very high. In
      this present work, a novel highly-efficient mono-component polymeric intumescent
      flame retardant, piperazine-modified ammonium polyphosphate (PA-APP) was
      prepared. The oxygen index value of PP containing 22 wt % of PA-APP reached
      31.2%, which increased by 58.4% compared with that of PP with equal amount of
      APP, and the vertical burning test (UL-94) could pass V-0 rating. Cone
      calorimeter (CC) results indicated that PP/PA-APP composite exhibited superior
      performance compared with PP/APP composite. For PP containing 25 wt % of PA-APP,
      fire growth rate (FGR) and smoke production rate (SPR) peak were reduced by 86.4%
      and 78.2%, respectively, compared with PP blended with 25 wt % APP. The relevant
      flame-retardant mechanism of PA-APP was investigated by Fourier transform
      infrared spectroscopy etc. The P-N-C structure with the alicyclic amine was
      formed during the thermal decomposition of piperazine salt (-NH2(+)-O-P-), and
      the rich P-N-C structure facilitated the formation of stable char layer at the
      later stage, consequently improving the flame-retardant efficiency of APP.

PMID- 24742306
TI  - Near-infrared fluorescence laparoscopy of the cystic duct and artery in pigs:
      performance of a preclinical dye.
AB  - BACKGROUND: Near-infrared fluorescence laparoscopy after intravenous indocyanine
      green (ICG) administration has been proposed as a promising surgical imaging
      technique for real-time visualization of the extrahepatic bile ducts and arteries
      in clinical laparoscopic cholecystectomies. However, optimization of this new
      technique with respect to the imaging system combined with the fluorophore is
      desirable. The performance of a preclinical near-infrared dye, CW800-CA, was
      compared with that of ICG for near-infrared fluorescence laparoscopy of the
      cystic duct and artery in pigs. MATERIALS AND METHODS: Laparoscopic
      cholecystectomy was performed in six pigs (average weight, 35 kg) using a
      commercially available laparoscopic fluorescence imaging system. The fluorophores
      CW800-CA and ICG (both 800 nm fluorescent dyes) were administered by intravenous
      injection in four and two pigs, respectively. CW800-CA was administered in three
      different doses (consecutively 0.25, 1, and 3 mg); ICG was intravenously injected
      (2.5 mg) for comparison. Intraoperative recognition of the biliary structures was
      recorded at set time points. The target-to-background ratio was determined to
      quantify the fluorescence signal of the designated tissues. RESULTS: A clinically
      proven dose of 2.5 mg of ICG resulted in a successful fluorescence delineation of
      both the cystic duct and artery. In the CW800-CA-injected pigs a clear
      visualization of the cystic duct and artery was obtained after administration of
      3 mg of CW800-CA. Time from injection until fluorescence identification of the
      cystic duct was reduced when CW800-CA was used compared with ICG (11.5 minutes
      versus 21.5 minutes, respectively). CW800-CA provided clearer illumination of the
      cystic artery, in terms of target-to-background ratio. CONCLUSIONS: As well as
      ICG, CW800-CA can be applied for fluorescence identification of the cystic artery
      and duct using a commercially available laparoscopic fluorescence imaging system.
      Fluorescence cholangiography of the cystic duct can be obtained earlier after
      intravenous injection of CW800-CA, compared with ICG. These findings increase the
      possibilities of use and of optimization of this imaging technique.

PMID- 24742307
TI  - Perceived visual informativeness (PVI): construct and scale development to assess
      visual information in printed materials.
AB  - There is a paucity of research on the visual images used in health communication
      messages and campaign materials. Even though many studies suggest further
      investigation of these visual messages and their features, few studies provide
      specific constructs or assessment tools for evaluating the characteristics of
      visual messages in health communication contexts. The authors conducted 2 studies
      to validate a measure of perceived visual informativeness (PVI), a message
      construct assessing visual messages presenting statistical or indexical
      information. In Study 1, a 7-item scale was created that demonstrated good
      internal reliability (alpha = .91), as well as convergent and divergent validity
      with related message constructs such as perceived message quality, perceived
      informativeness, and perceived attractiveness. PVI also converged with a
      preference for visual learning but was unrelated to a person's actual vision
      ability. In addition, PVI exhibited concurrent validity with a number of
      important constructs including perceived message effectiveness, decisional
      satisfaction, and three key public health theory behavior predictors: perceived
      benefits, perceived barriers, and self-efficacy. Study 2 provided more evidence
      that PVI is an internally reliable measure and demonstrates that PVI is a
      modifiable message feature that can be tested in future experimental work. PVI
      provides an initial step to assist in the evaluation and testing of visual
      messages in campaign and intervention materials promoting informed decision
      making and behavior change.

PMID- 24742308
TI  - Context matters: measuring implementation climate among individuals and groups.
AB  - BACKGROUND: It has been noted that implementation climate is positively
      associated with implementation effectiveness. However, issues surrounding the
      measurement of implementation climate, or the extent to which organizational
      members perceive that innovation use is expected, supported and rewarded by their
      organization remain. Specifically, it is unclear whether implementation climate
      can be measured as a global construct, whether individual or group-referenced
      items should be used, and whether implementation climate can be assessed at the
      group or organizational level. METHODS: This research includes two cross
      sectional studies with data collected via surveys at the individual level. The
      first study assessed the implementation climate perceptions of physicians
      participating in the National Cancer Institute's (NCI) Community Clinical
      Oncology Program (CCOP), and the second study assessed the perceptions of
      children's behavioral health clinicians implementing a treatment innovation. To
      address if implementation climate is a global construct, we used confirmatory
      factor analysis. To address how implementation climate should be measured and at
      what level, we followed a five-step framework outlined by van Mierlo and
      colleagues. This framework includes exploratory factor analysis and correlations
      to assess differences between individual and group-referenced items and
      intraclass correlations, interrater agreements, and exploratory factor analysis
      to determine if implementation climate can be assessed at the organizational
      level. RESULTS: The confirmatory factor analysis demonstrated that implementation
      climate is a global construct consisting of items related to expectations,
      support and rewards. There are mixed results, however, as to whether
      implementation climate should be measured using individual or group-referenced
      items. In our first study, where physicians were geographically dispersed and
      practice independently, there were no differences based on the type of items
      used, and implementation climate was an individual level construct. However, in
      the second study, in which clinicians practice in a central location and interact
      more frequently, group-referenced items may be appropriate. In addition,
      implementation climate could be considered an organizational level construct.
      CONCLUSIONS: The results are context-specific. Researchers should carefully
      consider the study setting when measuring implementation climate. In addition,
      more opportunities are needed to validate this measure and understand how well it
      predicts and explains implementation effectiveness.

PMID- 24742309
TI  - Neurodevelopmental outcomes in infants and children with single-suture
      craniosynostosis: a systematic review.
AB  - Children with single-suture craniosynostosis (SSC) are increasingly considered to
      be at high risk of adverse neurodevelopmental outcomes. This systematic review
      aimed to synthesise and critically appraise the existing literature on the
      neurodevelopmental features of SSC, with particular attention to methodological
      quality. A total of 33 articles based on 27 cohorts met inclusion criteria. In
      the context of variable methodological design and quality, most
      neurodevelopmental studies indicated that children with SSC are at increased risk
      for difficulties in cognitive, language, and motor domains during infancy (both
      pre- and post-surgery) and childhood. Limited information exists on factors
      influencing outcome. 

PMID- 24742311
TI  - Object-based mental rotation and visual perspective-taking in typical development
      and Williams syndrome.
AB  - This study examined Object-based (OB) rotation and Visual Perspective-Taking
      (VPT) abilities in Williams syndrome (WS) compared to typically developing (TD) 5
      10-year-olds. Extensive difficulties with both types of imagined rotation were
      observed in WS; WS performance was in line with the level of ability observed in
      TD 5-year-olds. However, an atypical pattern of errors on OB and VPT tasks was
      observed in WS compared to TD groups. Deficits in imagined rotations are
      consistent with known atypical cortical development in WS. Such difficulties in
      updating the position of the self following movement in WS may have implications
      for large-scale spatial navigation.

PMID- 24742310
TI  - Functional impairments in attention deficit hyperactivity disorder: the mediating
      role of neuropsychological functioning.
AB  - Attention deficit hyperactivity disorder (ADHD) is associated with multiple
      neuropsychological deficits and the present study aimed to investigate to what
      extent these deficits are related to the functional impairments associated with
      the disorder. The results showed that all executive functioning deficits and
      reaction time variability acted as mediators in the relation between ADHD and
      academic achievement. However, only the effect of working memory for language
      skills, and the effects of reaction time variability and working memory for
      mathematics, remained significant when studying independent effects. Regulation
      of anger was a significant mediator for peer problems. Gender or symptoms of
      oppositional defiant disorder (ODD) or conduct disorder (CD) did not moderate
      these findings.

PMID- 24742313
TI  - Primary reflex persistence in children with partial hearing.
AB  - Persistence of the asymmetrical tonic neck reflex (ATNR) was examined in children
      with partial hearing (aged 6-12 years). Core literacy skills were also assessed.
      Three groups of children were selected from three schools with special units for
      children with partial hearing. All children completed an upright ATNR test
      protocol and standardized tests of reading and spelling. Children with partial
      hearing had significant levels of ATNR persistence, and significant reading and
      spelling difficulties. The findings suggest that persistence of an early sub
      cortical reflex system may be associated with some of the motor and cognitive
      difficulties experienced by children with partial hearing. 

PMID- 24742312
TI  - The relationship between brain structure and cognition in transfused preterm
      children at school age.
AB  - Examine the relationship between brain structure and cognition in preterm
      children randomly assigned to a liberal red blood cell (RBC) transfusion strategy
      as neonates. Intelligence, achievement, and neuropsychological measures were
      assessed and structural imaging was obtained (n = 26; 38% male). Global brain
      volumes were related to cognitive outcome. Additionally, females performed lower
      on verbal fluency; lower performance was related to temporal white matter volume.
      Findings provide possible evidence of the adverse effect of a liberal RBC
      transfusion strategy in which females had decreased temporal lobe white matter
      directly related to poor verbal fluency. 

PMID- 24742314
TI  - Decrease social inequalities return-to-work: development and design of a
      randomised controlled trial among women with breast cancer.
AB  - BACKGROUND: Despite the improvement in the care management, women cancer patients
      who are still in employment find themselves for the most part obliged to stop
      working while they are having treatment. Their return-to-work probability is
      impacted by numerous psychosocial factors. The objective is to describe the
      development and the content of an intervention aimed to facilitate the return to
      work of female breast cancer patients and in particular the women in the most
      precarious situations through early active individualised psychosocial support
      (APAPI). METHODS: The intervention proposed is made up of 4 interviews with a
      psychologist at the hospital, distributed over the year according to the
      diagnosis and conducted on the same day as a conventional follow-up consultation,
      then a consultation with a specialist job retention physician. We expect, in the
      first instance, that this intervention will reduce the social inequalities of the
      return-to-work rate at 12 months. The EPICES score will enable the population to
      be broken down according to the level of social precariousness. The other
      expected results are the reduction of the social inequalities in the quality of
      the return to work at 18 and 24 months and the disparities between the individual
      and collective resources of the patients. This intervention is assessed in the
      context of a controlled and randomised multi-centre study. The patients eligible
      are women aged between 18 and 55 years with a unilateral breast cancer with local
      extension exclusively, having received surgery followed by adjuvant chemotherapy,
      in employment at the time of the diagnosis and dealt with by one of the 2
      investigating centres. DISCUSSION: It is essential to assess this type of
      intervention before envisaging its generalisation. The study set in place will
      enable us to measure the impact of this intervention aiming to facilitate the
      return to work of breast cancer patients, in particular for those who suffer from
      social fragility, compared with the standard care.

PMID- 24742315
TI  - Intermolecular hydroamination of 1,3-dienes catalyzed by
      bis(phosphine)carbodicarbene-rhodium complexes.
AB  - A carbodicarbene (CDC)-based pincer ligand scaffold is reported, along with its
      application to site-selective Rh(I)-catalyzed intermolecular hydroamination of
      1,3-dienes with aryl and alkyl amines. To the best of our knowledge, this is the
      first example of the use of a well-defined CDC complex as an efficient catalyst.
      Transformations proceed in the presence of 1.0-5.0 mol % Rh complex at 35-120 
      degrees C; allylic amines are obtained in up to 97% yield and with >98:2 site
      selectivity. 

PMID- 24742316
TI  - Closing the N-use efficiency gap to achieve food and environmental security.
AB  - To achieve food and environmental security, closing the gap between actual and
      attainable N-use efficiency should be as important as closing yield gaps. Using a
      meta-analysis of 205 published studies from 317 study sites, including 1332
      observations from rice, wheat, and maize system in China, reactive N (Nr) losses,
      and total N2O emissions from N fertilization both increased exponentially with
      increasing N application rate. On the basis of the N loss response curves from
      the literature meta-analysis, the direct N2O emission, NH3 volatilization, N
      leaching, and N runoff, and total N2O emission (direct + indirect) were
      calculated using information from the survey of farmers. The PFP-N (kilogram of
      harvested product per kilogram of N applied (kg (kg of N)(-1))) for 6259 farmers
      were relative low with only 37, 23, and 32 kg (kg of N)(-1) for rice, wheat, and
      maize systems, respectively. In comparison, the PFP-N for highest yield and PFP-N
      group (refers to fields where the PFP-N was within the 80-100th percentile among
      those fields that achieved yields within the 80-100th percentile) averaged 62,
      42, and 53 kg (kg of N)(-1) for rice, wheat, and maize systems, respectively. The
      corresponding grain yield would increase by 1.6-2.3 Mg ha(-1), while the N
      application rate would be reduced by 56-100 kg of N ha(-1) from average farmer
      field to highest yield and PFP-N group. In return, the Nr loss intensity (4-11 kg
      of N (Mg of grain)(-1)) and total N2O emission intensity (0.15-0.29 kg of N (Mg
      of grain)(-1)) would both be reduced significantly as compared to current
      agricultural practices. In many circumstances, closing the PFP-N gap in intensive
      cropping systems is compatible with increased crop productivity and reductions in
      both Nr losses and total N2O emissions. 

PMID- 24742317
TI  - Comparative analysis of the gonadal transcriptomes of the all-female species
      Poecilia formosa and its maternal ancestor Poecilia mexicana.
AB  - BACKGROUND: The Amazon molly, Poecilia formosa (Teleostei: Poeciliinae) is an
      unisexual, all-female species. It evolved through the hybridisation of two
      closely related sexual species and exhibits clonal reproduction by sperm
      dependent parthenogenesis (or gynogenesis) where the sperm of a parental species
      is only used to activate embryogenesis of the apomictic, diploid eggs but does
      not contribute genetic material to the offspring.Here we provide and describe the
      first de novo assembled transcriptome of the Amazon molly in comparison with its
      maternal ancestor, the Atlantic molly Poecilia mexicana. The transcriptome data
      were produced through sequencing of single end libraries (100 bp) with the
      Illumina sequencing technique. RESULTS: 83,504,382 reads for the Amazon molly and
      81,625,840 for the Atlantic molly were assembled into 127,283 and 78,961 contigs
      for the Amazon molly and the Atlantic molly, respectively. 63% resp. 57% of the
      contigs could be annotated with gene ontology terms after sequence similarity
      comparisons. Furthermore, we were able to identify genes normally involved in
      reproduction and especially in meiosis also in the transcriptome dataset of the
      apomictic reproducing Amazon molly. CONCLUSIONS: We assembled and annotated the
      transcriptome of a non-model organism, the Amazon molly, without a reference
      genome (de novo). The obtained dataset is a fundamental resource for future
      research in functional and expression analysis. Also, the presence of 30 meiosis
      specific genes within a species where no meiosis is known to take place is
      remarkable and raises new questions for future research.

PMID- 24742318
TI  - Molecular characterization of Plasmodium falciparum uracil-DNA glycosylase and
      its potential as a new anti-malarial drug target.
AB  - BACKGROUND: Based on resistance of currently used anti-malarials, a new anti
      malarial drug target against Plasmodium falciparum is urgently needed. Damaged
      DNA cannot be transcribed without prior DNA repair; therefore, uracil-DNA
      glycosylase, playing an important role in base excision repair, may act as a
      candidate for a new anti-malarial drug target. METHODS: Initially, the native
      PfUDG from parasite crude extract was partially purified using two columns, and
      the glycosylase activity was monitored. The existence of malarial UDG activity
      prompted the recombinant expression of PfUDG for further characterization. The
      PfUDG from chloroquine and pyrimethamine resistant P. falciparum strain K1 was
      amplified, cloned into the expression vector, and expressed in Escherichia coli.
      The recombinant PfUDG was analysed by SDS-PAGE and identified by LC-MS/MS. The
      three dimensional structure was modelled. Biochemical properties were
      characterized. Inhibitory effects of 12 uracil-derivatives on PfUDG activity were
      investigated. Inhibition of parasite growth was determined in vitro using SYBR
      Green I and compared with results from human cytotoxicity tests. RESULTS: The
      native PfUDG was partially purified with a specific activity of 1,811.7 units/mg
      (113.2 fold purification). After cloning of 966-bp PCR product, the 40-kDa hexa
      histidine tagged PfUDG was expressed and identified. The amino acid sequence of
      PfUDG showed only 24.8% similarity compared with the human enzyme. The
      biochemical characteristics of PfUDGs were quite similar. They were inhibited by
      uracil glycosylase inhibitor protein as found in other organisms. Interestingly,
      recombinant PfUDG was inhibited by two uracil-derived compounds; 1-methoxyethyl-6
      (p-n-octylanilino)uracil (IC50 of 16.75 MUM) and 6-(phenylhydrazino)uracil (IC50
      of 77.5 MUM). Both compounds also inhibited parasite growth with IC50s of 15.6
      and 12.8 MUM, respectively. Moreover, 1-methoxyethyl-6-(p-n-octylanilino)uracil
      was not toxic to HepG2 cells, with IC50 of > 160 MUM while 6
      (phenylhydrazino)uracil exhibited cytoxicity, with IC50 of 27.5 MUM. CONCLUSIONS:
      The recombinant PfUDG was expressed, characterized and compared to partially
      purified native PfUDG. Their characteristics were not significantly different.
      PfUDG differs from human enzyme in its size and predicted amino acid sequence.
      Two uracil derivatives inhibited PfUDG and parasite growth; however, only one non
      cytotoxic compound was found. Therefore, this selective compound can act as a
      lead compound for anti-malarial development in the future.

PMID- 24742319
TI  - Vintafolide (EC145) for the treatment of folate-receptor-alpha positive platinum
      resistant ovarian cancer.
AB  - Seminal advances in the treatment of cancer have been achieved because of drug
      development in ovarian cancer; notably the developments of platinums and taxanes.
      However, no new drug has been FDA approved for ovarian cancer since 2006, and the
      approval of an antiangiogenic agent for ovarian cancer in the US has stalled.
      Predicting the next breakthrough is a high risk and highly expensive venture. One
      of the most promising prospects is folate-receptor (FR)-targeted therapy, given
      the high expression in FR ovarian cancer. We review the development of
      vintafolide (EC145), a folic acid-desacetylvinblastine conjugate, the predictive
      utility of a FR-targeted imaging agent, technetium-(99)m-etarfolatide (EC20), the
      challenges in proving survival advantage, and other approaches to exploiting FR
      as a target in ovarian cancer.

PMID- 24742320
TI  - Enantioselective construction of [6,5,6]-carbocyclic systems by organo/metal
      catalyzed sequential reactions.
AB  - An efficient strategy for the enantioselective construction of [6,5,6]
      carbocyclic compounds has been established via one-pot reaction of (E)-4-(2
      ethynylphenyl)but-3-en-2-ones with maleimide sequentially catalyzed by cinchona
      alkaloid-based primary amine and gold complex (Ph3PAuNTf2). This methodology
      provided a facile approach to access the [6,5,6]-tricyclic skeleton in fairly
      good yield and with perfect enantioselectivities (98% to >99% ee). 

PMID- 24742321
TI  - Electronic states of tetrahydrofurfuryl alcohol (THFA) as studied by VUV
      spectroscopy and ab initio calculations.
AB  - The electronic spectroscopy of isolated tetrahydrofurfuryl alcohol (THFA) in the
      gas phase has been investigated using high-resolution photoabsorption
      spectroscopy in the 5.0-10.8 eV energy-range, with absolute cross-section
      measurements derived. The He(I) photoelectron spectrum was also collected to
      quantify ionization energies in the 9-16 eV spectral region. These experiments
      are supported by the first high-level ab initio calculations performed on the
      excited states of the neutral molecule and on the ground and excited state of the
      positive ion. The good agreement between the theoretical results and the
      measurements allows us to quantify for the first time the electronic-state
      spectroscopy of THFA. The present work also considers the question of the lowest
      energy conformers of the molecule and its population distribution at room
      temperature. 

PMID- 24742322
TI  - The Social Health Intervention Project (SHIP): protocol for a randomized
      controlled clinical trial assessing the effectiveness of a brief motivational
      intervention for problem drinking and intimate partner violence in an urban
      emergency department.
AB  - BACKGROUND: There is a strong reciprocal association between two highly prevalent
      public health problems: intimate partner violence and heavy drinking, both of
      which remain major sources of morbidity and mortality. Brief interventions in the
      Emergency Department setting have been found to be effective in reducing alcohol
      related injury but neither classic intimate partner violence nor substance abuse
      interventions have adequately integrated assessment and treatment for these co
      occurring conditions. The overall goal of this study is to determine whether a
      motivational intervention delivered at the time of an Emergency Department visit
      will reduce heavy drinking and improve the safety of women experiencing intimate
      partner violence. METHODS AND DESIGN: We are completing data collection for a
      randomized controlled trial enrolling 600 female patients, age 18-64, presenting
      to one of two urban Emergency Departments, who self-disclose both problem
      drinking and intimate partner violence. Eligible patients are randomized to a
      brief manual-guided motivational intervention, and a phone booster at 10 days.
      The intervention, which is delivered by masters-level therapists during the
      Emergency Department visit, is recorded and monitored for fidelity. Primary
      outcomes are episodes of heavy drinking and incidents of intimate partner
      violence, assessed weekly by Interactive Voice Response System for 12 weeks and
      at 3, 6 and 12 months by interviewers blinded to group assignment. To identify
      the impact of assessment alone, we included a no-contact control group assessed
      only once at 3 months. Secondary outcomes include violence severity, changes in
      the Composite Abuse Scale and alcohol quantity/frequency, along with other health
      related behaviors. The analysis will also explore the impact of likely mediators
      and moderators of the intervention. DISCUSSION: While screening and intervention
      for intimate partner violence is now recommended for women of child bearing age
      in health care settings, there is a need for rigorous evaluations of what works
      for whom. Upon completion, we will have high-quality evidence regarding the
      effectiveness of a low-intensity, brief motivational intervention, delivered by
      social workers in the Emergency Department setting, for decreasing episodes of
      heavy drinking and intimate partner violence. Ultimately, this is a model could
      be generalizable to other acute health care settings. TRIAL REGISTRATION:
      ClinicalTrials.gov REGISTRATION NUMBER: NCT01207258.

PMID- 24742324
TI  - Well-posedness of a density model for a population of theta neurons.
AB  - Population density models used to describe the evolution of neural populations in
      a phase space are closely related to the single neuron model that describes the
      individual trajectories of the neurons of the population and which gives in
      particular the phase-space where the computations are made. Based on a
      transformation of the quadratic integrate and fire single neuron model, the so
      called theta-neuron model is obtained and we shall introduce in this paper a
      corresponding population density model for it. Existence and uniqueness of a
      solution will be proved and some numerical simulations are presented.

PMID- 24742323
TI  - External validation of risk classification in patients with docetaxel-treated
      castration-resistant prostate cancer.
AB  - BACKGROUND: Castration-resistant prostate cancer (CRPC) patients have poor
      prognoses, and docetaxel (DTX) is among the few treatment options. An accurate
      risk classification to identify CRPC patient groups for which DTX would be
      effective is urgently warranted. The Armstrong risk classification (ARC), which
      classifies CRPC patients into 3 groups, is superior; however, its usefulness
      remains unclear, and further external validation is required before clinical use.
      This study aimed to examine the clinical significance of the ARC through external
      validation in DTX-treated Japanese CRPC patients. METHODS: CRPC patients who
      received 2 or more DTX cycles were selected for this study. Patients were
      classified into good-, intermediate-, and poor-risk groups according to the ARC.
      Prostate-specific antigen (PSA) responses and overall survival (OS) were
      calculated and compared between the risk groups. A multivariate analysis was
      performed to clarify the relationship between the ARC and major patient
      characteristics. RESULTS: Seventy-eight CRPC patients met the inclusion criteria.
      Median PSA levels at DTX initiation was 20 ng/mL. Good-, intermediate-, and poor
      risk groups comprised 51 (65%), 17 (22%), and 10 (13%) patients, respectively.
      PSA response rates >= 30% and >= 50% were 33%, 41%, and 30%, and 18%, 41%, and
      20% in the good-, intermediate-, and poor-risk groups, respectivcixely, with no
      significant differences (p = 0.133 and 0.797, respectively). The median OS in the
      good-, intermediate-, and poor-risk groups were statistically significant (p <
      0.001) at 30.1, 14.2, and 5.7 months, respectively. A multivariate analysis
      revealed that the ARC and PSA doubling time were independent prognostic factors.
      CONCLUSIONS: Most of CRPC patients were classified into good-risk group according
      to the ARC and the ARC could predict prognosis in DTX-treated CRPC patients.
      TRIAL REGISTRATION: University Hospital Medical Information Network Clinical
      Trials Registry (UMIN-CTR) number, UMIN000011969.

PMID- 24742325
TI  - Accumulation of natural killer cells in ischemic brain tissues and the
      chemotactic effect of IP-10.
AB  - BACKGROUND: Stroke is accompanied by a distinguished inflammatory reaction that
      is initiated by the infiltration of immunocytes, expression of cytokines, and
      other inflammatory mediators. As natural killer cells (NK cells) are a type of
      cytotoxic lymphocyte critical to the innate immune system, we investigated the
      mechanism of NK cells-induced brain injuries after cerebral ischemia and the
      chemotactic effect of IP-10 simultaneously. METHODS: NK cells infiltration,
      interferon-gamma (IFN-gamma) and IP-10 expression were detected by
      immunohistochemistry, immunofluorescence, PCR and flow cytometry in human and
      C57/BL6 wild type mouse ischemic brain tissues. The ischemia area was detected
      via 2,3,5-triphenyltetrazolium chloride staining. CXCR3 mean fluorescence
      intensity of isolated NK cells was measured by flow cytometry. The neuronal
      injury made by NK cells was examined via apoptosis experiment. The chemotactic of
      IP-10 was detected by migration and permeability assays. RESULTS: In human
      ischemic brain tissue, infiltrations of NK cells were observed and reached a peak
      at 2 to 5 days. In a permanent middle cerebral artery occlusion (pMCAO) model,
      infiltration of NK cells into the ischemic infarct region reached their highest
      levels 12 hours after ischemia. IFN-gamma-positive NK cells and levels of the
      chemokine IP-10 were also detected within the ischemic region, from 6 hours up to
      4 days after pMCAO was performed, and IFN-gamma levels decreased after NK cells
      depletion in vivo. Co-culture experiments of neural cells with NK cells also
      showed that neural necrosis was induced via IFN-gamma. In parallel experiments
      with IP-10, the presence of CXCR3 indicates that NK cells were affected by IP-10
      via CXCR3, and the effect was dose-dependent. After IP-10 depletion in vivo, NK
      cells decreased. In migration assays and permeability experiments, disintegration
      of the blood-brain barrier (BBB) was observed following the addition of NK cells.
      Moreover, in the presence of IP-10 this injury was aggravated. CONCLUSIONS: All
      findings support the hypothesis that NK cells participate in cerebral ischemia
      and promote neural cells necrosis via IFN-gamma. Moreover, IP-10 intensifies
      injury to the BBB by NK cells via CXCR3.

PMID- 24742326
TI  - HIV testing trends: Southeastern Pennsylvania, 2002-2010.
AB  - There are limited data on HIV testing trends after 2006 when the Centers for
      Disease Control and Prevention (CDC) introduced opt-out HIV testing with the aims
      of identifying HIV-infected persons early and linking them to care. We used data
      from the Southeastern Pennsylvania Household Health Survey between 2002 and 2010
      to evaluate HIV testing over time. 50,698 adult (>=18 years) survey respondents
      were included. HIV testing increased after the CDC recommendations: 42.1% of
      survey respondents received testing at least once in 2002 versus 51.4% in 2010,
      p<0.001. Testing trends increased among all demographic groups, but existing
      differences in testing before 2006 persisted after that year as follows: younger
      patients, racial/ethnic minorities, patients on Medicaid were all more likely to
      get tested than their counterparts. Blacks and patients seeking care in community
      health centers had the fastest rise in HIV testing. The probability of HIV
      testing in Blacks was 0.56 (95% CI 0.54-0.60) in 2002 and increased to 0.73 (0.70
      0.76) by 2010. Patients seeking care in community health centers had a
      probability of HIV testing of 0.57 (0.47-0.66) in 2002, which increased to 0.69
      (0.60-0.77) by 2010. In comparison, patients in private clinics had an HIV
      testing probability of 0.40 (0.36-0.43) in 2002 compared to 0.47 (0.40-0.54) in
      2010. HIV testing is increasing, particularly among ethnic minorities and in
      community health centers. However, testing remains to be improved in that setting
      and across all clinic types.

PMID- 24742327
TI  - Protein-to-mRNA ratios are conserved between Pseudomonas aeruginosa strains.
AB  - Recent studies have shown that the concentrations of proteins expressed from
      orthologous genes are often conserved across organisms and to a greater extent
      than the abundances of the corresponding mRNAs. However, such studies have not
      distinguished between evolutionary (e.g., sequence divergence) and environmental
      (e.g., growth condition) effects on the regulation of steady-state protein and
      mRNA abundances. Here, we systematically investigated the transcriptome and
      proteome of two closely related Pseudomonas aeruginosa strains, PAO1 and PA14,
      under identical experimental conditions, thus controlling for environmental
      effects. For 703 genes observed by both shotgun proteomics and microarray
      experiments, we found that the protein-to-mRNA ratios are highly correlated
      between orthologous genes in the two strains to an extent comparable to protein
      and mRNA abundances. In spite of this high molecular similarity between PAO1 and
      PA14, we found that several metabolic, virulence, and antibiotic resistance genes
      are differentially expressed between the two strains, mostly at the protein but
      not at the mRNA level. Our data demonstrate that the magnitude and direction of
      the effect of protein abundance regulation occurring after the setting of mRNA
      levels is conserved between bacterial strains and is important for explaining the
      discordance between mRNA and protein abundances. 

PMID- 24742328
TI  - Structural genomics analysis of uncharacterized protein families overrepresented
      in human gut bacteria identifies a novel glycoside hydrolase.
AB  - BACKGROUND: Bacteroides spp. form a significant part of our gut microbiome and
      are well known for optimized metabolism of diverse polysaccharides. Initial
      analysis of the archetypal Bacteroides thetaiotaomicron genome identified 172
      glycosyl hydrolases and a large number of uncharacterized proteins associated
      with polysaccharide metabolism. RESULTS: BT_1012 from Bacteroides
      thetaiotaomicron VPI-5482 is a protein of unknown function and a member of a
      large protein family consisting entirely of uncharacterized proteins. Initial
      sequence analysis predicted that this protein has two domains, one on the N- and
      one on the C-terminal. A PSI-BLAST search found over 150 full length and over 90
      half size homologs consisting only of the N-terminal domain. The experimentally
      determined three-dimensional structure of the BT_1012 protein confirms its two
      domain architecture and structural analysis of both domains suggests their
      specific functions. The N-terminal domain is a putative catalytic domain with
      significant similarity to known glycoside hydrolases, the C-terminal domain has a
      beta-sandwich fold typically found in C-terminal domains of other glycosyl
      hydrolases, however these domains are typically involved in substrate binding. We
      describe the structure of the BT_1012 protein and discuss its sequence-structure
      relationship and their possible functional implications. CONCLUSIONS: Structural
      and sequence analyses of the BT_1012 protein identifies it as a glycosyl
      hydrolase, expanding an already impressive catalog of enzymes involved in
      polysaccharide metabolism in Bacteroides spp. Based on this we have renamed the
      Pfam families representing the two domains found in the BT_1012 protein, PF13204
      and PF12904, as putative glycoside hydrolase and glycoside hydrolase-associated C
      terminal domain respectively.

PMID- 24742329
TI  - Delayed gastric emptying after esophagectomy for malignancy.
AB  - BACKGROUND: Controversy still exists about the need for pyloric drainage
      procedures after esophagectomy with gastric conduit reconstruction. Although
      pyloric drainage may prevent postoperative delayed gastric emptying (DGE), it may
      also promote dumping syndrome and bile reflux. The aims of this study were to
      audit the incidence and management of DGE in patients without routine pyloric
      drainage after esophagectomy in a university medical center. PATIENTS AND
      METHODS: From July 2006 to June 2012, data from 356 consecutive patients who
      underwent esophagectomy with a gastric conduit without pyloric drainage for
      esophageal or gastric cardia carcinoma were reviewed. Major observation
      parameters were the incidence, management, and outcomes of DGE. RESULTS: Overall
      incidence of DGE was 15.7% (56 of 356). Early DGE developed in 26 patients, and
      late DGE developed in 30 patients. There were no differences in demographic and
      intraoperative data between the two groups with or without DGE. More DGE was
      documented in patients with an intra-right thoracic gastric conduit (P=.031). A
      higher incidence of postoperative pneumonia was observed in patients exhibiting
      early DGE, but without significance (P=.254). There were also no significant
      impacts on respiratory failure (P=.848) and anastomotic leakage (P=.257). There
      was an increased postoperative hospital stay with DGE, but without significance
      (P=.089). Endoscopic balloon dilatation of the pylorus was used to manage 33.9%
      of patients with DGE, yielding a 78.9% (15 of 19) success rate without
      complications. In 3 patients endoscopy showed the pylorus was open, and their
      symptoms improved over time. One patient with tumor-related DGE was treated by
      pyloric stent. The remaining patients were adequately treated with conservative
      management. CONCLUSIONS: Omitting the operative drainage procedure does not lead
      to an increased frequency of DGE after esophagectomy with a gastric conduit. Many
      patients responded to conservative management, and endoscopic balloon pyloric
      dilatation can be effective in managing the DGE postoperatively.

PMID- 24742330
TI  - Somatostatin receptor expression in Merkel cell carcinoma as target for molecular
      imaging.
AB  - BACKGROUND: Merkel cell carcinoma (MCC) is a rare cutaneous neoplasm with
      increasing incidence, aggressive behavior and poor prognosis. Somatostatin
      receptors (SSTR) are expressed in MCC and represent a potential target for both
      imaging and treatment. METHODS: To non-invasively assess SSTR expression in MCC
      using PET and the radiotracers [68Ga]DOTA-D-Phe1-Tyr3-octreotide (DOTATOC) or 
      octreotate (DOTATATE) as surrogate for tumor burden. In 24 patients with
      histologically proven MCC SSTR-PET was performed and compared to results of
      computed tomography (CT). RESULTS: SSTR-PET detected primary and metastatic MCC
      lesions. On a patient-based analysis, sensitivity of SSTR-PET was 73% for nodal
      metastases, 100% for bone, and 67% for soft-tissue metastases, respectively.
      Notably, brain metastases were initially detected by SSTR-PET in 2 patients,
      whereas liver and lung metastases were diagnosed exclusively by CT. SSTR-PET
      showed concordance to CT results in 20 out of 24 patients. Four patients (17%)
      were up-staged due to SSTR-PET and patient management was changed in 3 patients
      (13%). CONCLUSION: SSTR-PET showed high sensitivity for imaging bone, soft tissue
      and brain metastases, and particularly in combination with CT had a significant
      impact on clinical stage and patient management.

PMID- 24742331
TI  - Co-Fe nanodumbbells: synthesis, structure, and magnetic properties.
AB  - We report the solution phase synthesis, the structural analysis, and the magnetic
      properties of hybrid nanostructures combining two magnetic metals. These nano
      objects are characterized by a remarkable shape, combining Fe nanocubes on Co
      nanorods. The topological composition, the orientation relationship, and the
      growth steps have been studied by advanced electron microscopy techniques, such
      as HRTEM, electron tomography, and state-of-the-art 3-dimensional elemental
      mapping by EDX tomography. The soft iron nanocubes behave as easy nucleation
      centers that induce the magnetization reversal of the entire nanohybrid, leading
      to a drastic modification of the overall effective magnetic anisotropy. 

PMID- 24742332
TI  - Characterizing compatibility and agreement of unrooted trees via cuts in graphs.
AB  - BACKGROUND: Deciding whether there is a single tree -a supertree- that summarizes
      the evolutionary information in a collection of unrooted trees is a fundamental
      problem in phylogenetics. We consider two versions of this question: agreement
      and compatibility. In the first, the supertree is required to reflect precisely
      the relationships among the species exhibited by the input trees. In the second,
      the supertree can be more refined than the input trees. Testing for compatibility
      is an NP-complete problem; however, the problem is solvable in polynomial time
      when the number of input trees is fixed. Testing for agreement is also NP
      complete, but it is not known whether it is fixed-parameter tractable.
      Compatibility can be characterized in terms of the existence of a specific kind
      of triangulation in a structure known as the display graph. Alternatively, it can
      be characterized as a chordal graph sandwich problem in a structure known as the
      edge label intersection graph. No characterization of agreement was known.
      RESULTS: We present a simple and natural characterization of compatibility in
      terms of minimal cuts in the display graph, which is closely related to
      compatibility of splits. We then derive a characterization for agreement.
      CONCLUSIONS: Explicit characterizations of tree compatibility and agreement are
      essential to finding practical algorithms for these problems. The simplicity of
      the characterizations presented here could help to achieve this goal.

PMID- 24742333
TI  - E2F1 renders prostate cancer cell resistant to ICAM-1 mediated antitumor immunity
      by NF-kappaB modulation.
AB  - BACKGROUND: E2F1 is the gatekeeper of the cell cycle controlling an analogous
      balance between proliferation and cell death. E2F1 expression is elevated in
      advanced prostate cancer. However, it is still unclear that the roles and
      mechanisms of E2F1 on prostate cancers. METHODS: Targeted knockdown by interferon
      RNA was applied on two prostate cancer and Hela cell lines to examine the inverse
      correlation expression of E2F1 and ICAM-1. ICAM-1 promoter reporter and ChIP
      assays were used for analysis of the molecular basis of transcriptional
      regulation of E2F1 on ICAM-1. Co-IP assays were employed for testing the protein
      interaction between E2F1 and NF-kappaB. Tumor xenograft mice model with E2F1 and
      ICAM-1-knockdown prostate cancer cells were used to investigate the effects of
      E2F1 and ICAM-1 on antitumor immunity. RESULTS: E2F1 knockdown by a specific
      short hairpin RNA increased gene transcription and protein expression of ICAM-1.
      By using wild type and a series of mutant ICAM-1 promoter luciferase constructs,
      the NF-kappaB binding sites were found to be important for E2F1 regulation of
      ICAM-1 promoter. Targeted knockdown of E2F1 did not affect expression and
      phosphorylation of NF-kappaB and IkappaBalpha, but facilitated NF-kappaB binding
      to the ICAM-1 promoter, subsequently induced ICAM-1 transcription and production
      in prostate carcinoma cells. Furthermore, knockdown of E2F1 inhibited tumor
      growth of prostate cancer in vivo through increasing the susceptibility of tumor
      cells to ICAM-1-mediated anti-tumor immunity including enhancement of monocyte
      adhesion, leucocytes infiltration, as well as cytotoxicity against tumor cells.
      CONCLUSIONS: E2F1 knockdown inhibited prostate tumor growth in vitro and in vivo
      through sensitizing tumor cells to ICAM-1 mediated anti-immunity by NF-kappaB
      modulation, highlighting the potential of E2F1 as a therapeutic target.

PMID- 24742334
TI  - Influence of lag effect, soil release, and climate change on watershed
      anthropogenic nitrogen inputs and riverine export dynamics.
AB  - This study demonstrates the importance of the nitrogen-leaching lag effect, soil
      nitrogen release, and climate change on anthropogenic N inputs (NANI) and
      riverine total nitrogen (TN) export dynamics using a 30-yr record for the Yongan
      River watershed in eastern China. Cross-correlation analysis indicated a 7-yr, 5
      yr, and 4-yr lag time in riverine TN export in response to changes in NANI,
      temperature, and drained agricultural land area, respectively. Enhanced by warmer
      temperature and improved agricultural drainage, the upper 20 cm of agricultural
      soils released 270 kg N ha(-1) between 1980 and 2009. Climate change also
      increased the fractional export of NANI to river. An empirical model (R(2) =
      0.96) for annual riverine TN flux incorporating these influencing factors
      estimated 35%, 41%, and 24% of riverine TN flux originated from the soil N pool,
      NANI, and background N sources, respectively. The model forecasted an increase of
      45%, 25%, and 6% and a decrease of 13% in riverine TN flux from 2010 to 2030
      under continued development, climate change, status-quo, and tackling scenarios,
      respectively. The lag effect, soil N release, and climate change delay riverine
      TN export reductions with respect to decreases in NANI and should be considered
      in developing and evaluating N management measures. 

PMID- 24742335
TI  - Discovery of amphipathic dynorphin A analogues to inhibit the neuroexcitatory
      effects of dynorphin A through bradykinin receptors in the spinal cord.
AB  - We hypothesized that under chronic pain conditions, up-regulated dynorphin A (Dyn
      A) interacts with bradykinin receptors (BRs) in the spinal cord to promote
      hyperalgesia through an excitatory effect, which is opposite to the well-known
      inhibitory effect of opioid receptors. Considering the structural dissimilarity
      between Dyn A and endogenous BR ligands, bradykinin (BK) and kallidin (KD), this
      interaction could not be predicted, but it allowed us to discover a potential
      neuroexcitatory target. Well-known BR ligands, BK, [des-Arg(10), Leu(9)]-kallidin
      (DALKD), and HOE140 showed different binding profiles at rat brain BRs than that
      previously reported. These results suggest that neuronal BRs in the rat central
      nervous system (CNS) may be pharmacologically distinct from those previously
      defined in non-neuronal tissues. Systematic structure-activity relationship (SAR)
      study at the rat brain BRs was performed, and as a result, a new key structural
      feature of Dyn A for BR recognition was identified: amphipathicity. NMR studies
      of two lead ligands, Dyn A-(4-11) 7 and [des-Arg(7)]-Dyn A-(4-11) 14, which
      showed the same high binding affinity, confirmed that the Arg residue in position
      7, which is known to be crucial for Dyn A's biological activity, is not
      necessary, and that a type I beta-turn structure at the C-terminal part of both
      ligands plays an important role in retaining good binding affinities at the BRs.
      Our lead ligand 14 blocked Dyn A-(2-13) 10-induced hyperalgesic effects and motor
      impairment in in vivo assays using naive rats. In a model of peripheral
      neuropathy, intrathecal (i.th.) administration of ligand 14 reversed thermal
      hyperalgesia and mechanical hypersensitivity in a dose-dependent manner in nerve
      injured rats. Thus, ligand 14 may inhibit abnormal pain states by blocking the
      neuroexcitatory effects of enhanced levels of Dyn A, which are likely to be
      mediated by BRs in the spinal cord. 

PMID- 24742336
TI  - Coenzyme Q10 supplementation and multiple sclerosis.

PMID- 24742337
TI  - Photodecarbonylation mechanism of cyclopropenone in the gas phase: electronic
      structure calculation and AIMS dynamics simulation.
AB  - In this article, structures and energies of cyclopropenone in the low-lying
      electronic states have been determined by the CASSCF and MS-CASPT2 calculations
      with different basis sets. Two minimum-energy conical intersections (CI-1 and CI
      2) between S0 and S1 were obtained and their topographic characters were
      characterized by the SA4-CAS(10,9) calculated energy gradients and nonadiabatic
      coupling vectors. The AIMS method was used to carry out nonadiabatic dynamics
      simulation with ab initio calculation performed at the SA4-CAS(10,9) level. On
      the basis of time evolution of wave functions simulated here, the S1 lifetime is
      fitted to be 125 fs with a pure exponential decay for the S1 electronic
      population. The CI-1 intersection is mainly responsible for ultrafast S1->S0
      nonadiabatic transition and the photoinduced decarbonylation is a sequential
      process, where the first C-C bond is broken in the S1 state and fission of the
      second C-C bond occurs in the S0 state as a result of the S1->S0 internal
      conversion via the CI-1 region. As a minor channel through the CI-2 region, the
      decarbonylation proceeds in an asynchronous concerted way. Effects of the S1
      excess energies and the S1-S0 energy gap on the nonadiabatic dynamics were
      examined, which reveals that the S1->S0 nonadiabatic transition occurs within a
      small energy gap and high-energy conical intersection regions can play an
      important role. The present study provides new insights into mechanistic
      photochemistry of cyclopropenones and reveals that the AIMS dynamics simulation
      at a high-accuracy ab initio level is a powerful tool for exploring a mechanism
      of an ultrafast photochemical reaction. 

PMID- 24742338
TI  - Characterization of host immune responses in Ebola virus infections.
AB  - Ebola causes highly lethal hemorrhagic fever in humans with no licensed
      countermeasures. Its virulence can be attributed to several immunoevasion
      mechanisms: an early inhibition of innate immunity started by the downregulation
      of type I interferon, epitope masking and subversion of the adaptive humoural
      immunity by secreting a truncated form of the viral glycoprotein. Deficiencies in
      specific and non-specific antiviral responses result in unrestricted viral
      replication and dissemination in the host, causing death typically within 10 days
      after the appearance of symptoms. This review summarizes the host immune response
      to Ebola infection, and highlights the short- and long-term immune responses
      crucial for protection, which holds implications for the design of future
      vaccines and therapeutics.

PMID- 24742339
TI  - 3D imaging of the early embryonic chicken heart with focused ion beam scanning
      electron microscopy.
AB  - Early embryonic heart development is a period of dynamic growth and remodeling,
      with rapid changes occurring at the tissue, cell, and subcellular levels. A
      detailed understanding of the events that establish the components of the heart
      wall has been hampered by a lack of methodologies for three-dimensional (3D),
      high-resolution imaging. Focused ion beam scanning electron microscopy (FIB-SEM)
      is a novel technology for imaging 3D tissue volumes at the subcellular level. FIB
      SEM alternates between imaging the block face with a scanning electron beam and
      milling away thin sections of tissue with a FIB, allowing for collection and
      analysis of 3D data. FIB-SEM was used to image the three layers of the day 4
      chicken embryo heart: myocardium, cardiac jelly, and endocardium. Individual
      images obtained with FIB-SEM were comparable in quality and resolution to those
      obtained with transmission electron microscopy. Up to 1,100 serial images were
      obtained in 4 nm increments at 4.88 nm resolution, and image stacks were aligned
      to create volumes 800-1,500 MUm3 in size. Segmentation of organelles revealed
      their organization and distinct volume fractions between cardiac wall layers. We
      conclude that FIB-SEM is a powerful modality for 3D subcellular imaging of the
      embryonic heart wall. 

PMID- 24742340
TI  - Pulsed-laser deposition of nanostructured iron oxide catalysts for efficient
      water oxidation.
AB  - Amorphous iron oxide nanoparticles were synthesized by pulsed-laser deposition
      (PLD) for functionalization of indium-tin oxide surfaces, resulting in electrodes
      capable of efficient catalysis in water oxidation. These electrodes, based on
      earth-abundant and nonhazardous iron metal, are able to sustain high current
      densities (up to 20 mA/cm2) at reasonably low applied potential (1.64 V at pH
      11.8 vs reversible hydrogen electrode) for more than 1 h when employed as anodes
      for electrochemical water oxidation. The good catalytic performance proves the
      validity of PLD as a method to prepare nanostructured solid-state materials for
      catalysis, enabling control over critical properties such as surface coverage and
      morphology.

PMID- 24742342
TI  - Louse-borne relapsing fever profile at Felegehiwot referral hospital, Bahir Dar
      city, Ethiopia: a retrospective study.
AB  - BACKGROUND: Louse- borne relapsing fever is an acute febrile illness caused by
      Borrelia recurrentis and is transmitted by body lice, Pediculus humanus corporis.
      The disease has occurred as epidemic in different parts of the country.Therefore,
      the aim of this retrospective study was conducted to assess the LBRF profile for
      the last four years. METHODS: A retrospective study was conducted on patients
      with LBRF admitted from 2009-2012 at Felegehiwot referral hospital. The diagnosis
      was based on both clinical and laboratory methods. Patients with strong clinical
      suspicion of LBRF and positive for Borrelia species in their blood was diagnosed
      as LBRF cases. Data was collected from all patients with LBRF- like symptoms in
      their registration book. Data was checked for completeness, coded and analysed
      using SPSS version 16. P < 0.05 was considered significant for comparison.
      RESULTS: Of the 4559 patients admitted with LBRF- like symptoms, 4178 (91.6%)
      were males and 381 (8.4%) were females. Most of the patients (74.2%) were within
      age groups 11-20 years. The majority of patients (94.4%) were from urban
      residence. The overall prevalence of LBRF was 225 (4.9%) and the highest
      prevalence 171 (5.1%) was observed in age groups of 11-20 years. The association
      between seasonal variation and prevalence of LBRF showed that more patients with
      positive for Borrelia species were recorded in dry 27 (9.7%) than wet 198 (4.6%)
      seasons (P < 0.001). Finally, a trend in prevalence of LBRF for the last four
      years showed that the highest numbers of cases were documented in 2010.
      CONCLUSION: The overall prevalence of LBRF was high and the highest prevalence
      was observed in young age groups. Moreover, most of the patients with LBRF were
      from urban dwellers. Therefore, health education should be delivered towards LBRF
      prevention in the city.

PMID- 24742341
TI  - Rationale and design of the Investigator-Steered Project on Intravascular Renal
      Denervation for Management of Drug-Resistant Hypertension (INSPiRED) trial.
AB  - The SYMPLICITY studies showed that renal denervation (RDN) is feasible as novel
      treatment for resistant hypertension. However, RDN is a costly and invasive
      procedure, the long-term efficacy and safety of which has not yet been proven.
      Therefore, we designed the INSPiRED trial to compare the blood pressure lowering
      efficacy and safety of RDN vs usual medical therapy. INSPiRED is a randomized
      controlled trial enrolling 240 treatment-resistant hypertensive patients at 16
      expert hypertension centres in Belgium. Eligible patients, aged 20-69 years old,
      have a 24-h ambulatory blood pressure of 130 mmHg systolic or 80 mmHg diastolic
      or more, while taking at least three antihypertensive drugs. They are randomized
      to RDN (EnligHTN(TM), SJM system) plus usual care (intervention group) or usual
      care alone (control group) in a ratio of 1:1. The primary endpoints for efficacy
      and safety, measured after 6 months, are the baseline-adjusted between-group
      differences in 24h systolic blood pressure and in glomerular filtration rate as
      estimated by the Chronic Kidney Disease Epidemiology Collaboration equation.
      Follow-up will continue up to 36 months after randomization. INSPiRED is powered
      to demonstrate a 10-mmHg difference in systolic blood pressure between randomized
      groups with a two-sided p-value of 0.01 and 90% power. It will generate long-term
      efficacy and safety data, identify the subset of treatment-resistant hypertensive
      patients responsive to RDN, provide information on cost-effectiveness, and by
      doing so INSPiRED will inform guideline committees and health policy makers.
      TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT 01505010.

PMID- 24742343
TI  - Incorporating Mindfulness and Chat Groups Into an Online Cognitive Behavioral
      Therapy for Mixed Female Sexual Problems.
AB  - The current randomized study evaluated an online cognitive behavioral therapy
      program for female sexual problems. PursuingPleasure (PP) consisted of six online
      modules that included psychoeducation, sensate focus, communication exercises,
      cognitive exercises, and e-mail contact with a therapist. PP incorporated
      mindfulness training and online chat groups as well as assessed partner sexual
      functioning. Participants demonstrated a completion rate of 57%, with 26 women
      with female sexual problems and related distress completing the program compared
      to a wait-list control group of 31 women also experiencing sexual problems and
      distress. Sexual problems reported by women in both groups included difficulties
      with sexual desire, arousal, orgasm, and pain. The treatment group demonstrated
      significant improvements in all domains of female sexual response (except for
      sexual pain) and significant reductions in the reported frequency of sexual
      problems and distress. Partner sexual functioning showed positive change.
      Improvements in female sexual functioning and some improvements in male partner
      sexual functioning were maintained at three-month follow-up. Limitations and
      suitability of clients for this treatment approach for women who are
      geographically isolated, who are unable to attend face-to-face therapy, and who
      possess a high degree of motivation are discussed. 

PMID- 24742344
TI  - Cross-correlations and joint gaussianity in multivariate level crossing models.
AB  - A variety of phenomena in physical and biological sciences can be mathematically
      understood by considering the statistical properties of level crossings of random
      Gaussian processes. Notably, a growing number of these phenomena demand a
      consideration of correlated level crossings emerging from multiple correlated
      processes. While many theoretical results have been obtained in the last decades
      for individual Gaussian level-crossing processes, few results are available for
      multivariate, jointly correlated threshold crossings. Here, we address bivariate
      upward crossing processes and derive the corresponding bivariate Central Limit
      Theorem as well as provide closed-form expressions for their joint level-crossing
      correlations. 

PMID- 24742345
TI  - From diagnosis to engagement in HIV care: assessment and predictors of linkage
      and retention in care among patients diagnosed by emergency department based
      testing in an urban public hospital.

PMID- 24742346
TI  - Hepatitis A infection in patients with chronic viral liver disease: a cross
      sectional study in Jahrom, Iran.
AB  - Infection with hepatitis A virus (HAV) in patient with chronic liver disease
      (CLD; due to hepatitis B or hepatitis C) may cause severe disease and fulminant
      liver failure. This study aimed to determine the seroprevalence of HAV antibodies
      in patients infected with HCV or HBV in Iran (Jahrom city). A total of 159
      patients with underlying CLD were recruited between September 2012 and February
      2013. Serum samples were collected from each patient and tested for anti-HAV
      using enzyme-linked immunosorbent assay (ELISA). The overall seroprevalence of
      total anti-HAV was 79.2%. Patients aged 20-30 years had the lowest (28.3%) anti
      HAV seropositivity and those aged >50 years had the highest (95%) seropositivity.
      The overall prevalence of anti-HAV in patients with chronic HCV and HBV infection
      was 93.7% and 77.1%, respectively. The anti-HAV seropositivity in liver cirrhosis
      patients was 100% compared to CLD patients. Because of low HAV immunity in
      younger CLD patients, vaccination against HAV should be considered.

PMID- 24742349
TI  - Ce(OTf)3-catalyzed [3 + 2] cycloaddition of azides with nitroolefins:
      regioselective synthesis of 1,5-disubstituted 1,2,3-triazoles.
AB  - The first example of rare earth metal-catalyzed [3 + 2] cycloaddition of organic
      azides with nitroolefins and subsequent elimination reaction is described. In the
      presence of a catalytic amount of Ce(OTf)3, both benzyl and phenyl azides react
      with a broad range of aryl nitroolefins containing a range of functionalities
      selectively producing 1,5-disubstituted 1,2,3-triazoles in good to excellent
      yields. 

PMID- 24742347
TI  - HIV-1 Tat second exon limits the extent of Tat-mediated modulation of interferon
      stimulated genes in antigen presenting cells.
AB  - BACKGROUND: We have shown that HIV-1 Tat interaction with MAP2K3, MAP2K6, and
      IRF7 promoters is key to IFN-stimulated genes (ISG) activation in immature
      dendritic cells and macrophages. RESULTS: We evaluated how Tat alleles and
      mutants differ in cellular gene modulation of immature dendritic cells and
      monocyte-derived macrophages and what similarities this modulation has with that
      induced by interferons. The tested alleles and mutants modulated to different
      degrees ISG, without concomitant induction of interferons. The first exon TatSF21
      72 and the minimal transactivator TatSF21-58, all modulated genes to a
      significantly greater extent than full-length wild type, two-exon Tat, indicating
      that Tat second exon is critical in reducing the innate response triggered by HIV
      1 in these cells. Mutants with reduced LTR transactivation had a substantially
      reduced effect on host gene expression modulation than wild type TatSF2. However,
      the more potent LTR transactivator TatSF2A58T modulated ISG expression to a lower
      degree compared to TatSF2. A cellular gene modulation similar to that induced by
      Tat and Tat mutants in immature dendritic cells could be observed in monocyte
      derived macrophages, with the most significant pathways affected by Tat being the
      same in both cell types. Tat expression in cells deleted of the type I IFN locus
      or receptor resulted in a gene modulation pattern similar to that induced in
      primary immature dendritic cells and monocyte-derived macrophages, excluding the
      involvement of type I IFNs in Tat-mediated gene modulation. ISG activation
      depends on Tat interaction with MAP2K3, MAP2K6, and IRF7 promoters and a single
      exon Tat protein more strongly modulated the luciferase activity mediated by
      MAP2K3, MAP2K6, and IRF7 promoter sequences located 5' of the RNA start site than
      the wild type two-exon Tat, while a cysteine and lysine Tat mutants, reduced in
      LTR transactivation, had negligible effects on these promoters. Chemical
      inhibition of CDK9 or Sp1 decreased Tat activation of MAP2K3-, MAP2K6-, and IRF7
      mediated luciferase transcription. CONCLUSIONS: Taken together, these data
      indicate that the second exon of Tat is critical to the containment of the innate
      response stimulated by Tat in antigen presenting cells and support a role for Tat
      in stimulating cellular transcription via its interaction with transcription
      factors present at promoters.

PMID- 24742351
TI  - Probabilistic drug connectivity mapping.
AB  - BACKGROUND: The aim of connectivity mapping is to match drugs using drug
      treatment gene expression profiles from multiple cell lines. This can be viewed
      as an information retrieval task, with the goal of finding the most relevant
      profiles for a given query drug. We infer the relevance for retrieval by data
      driven probabilistic modeling of the drug responses, resulting in probabilistic
      connectivity mapping, and further consider the available cell lines as different
      data sources. We use a special type of probabilistic model to separate what is
      shared and specific between the sources, in contrast to earlier connectivity
      mapping methods that have intentionally aggregated all available data, neglecting
      information about the differences between the cell lines. RESULTS: We show that
      the probabilistic multi-source connectivity mapping method is superior to
      alternatives in finding functionally and chemically similar drugs from the
      Connectivity Map data set. We also demonstrate that an extension of the method is
      capable of retrieving combinations of drugs that match different relevant parts
      of the query drug response profile. CONCLUSIONS: The probabilistic modeling-based
      connectivity mapping method provides a promising alternative to earlier methods.
      Principled integration of data from different cell lines helps to identify
      relevant responses for specific drug repositioning applications.

PMID- 24742352
TI  - "Off-clamp, non-renorrhaphy" laparoscopic partial nephrectomy with perirenal fat
      and Gerota's fascia reapproximation: initial experience and perioperative
      outcomes.
AB  - PURPOSE: To describe our initial experience of "off-clamp, non-renorrhaphy"
      laparoscopic partial nephrectomy (OCNR-LPN) with perirenal fat and Gerota's
      fascia reapproximation technique. PATIENTS AND METHODS: Between August 2012 and
      March 2013, 24 consecutive patients underwent OCNR-LPN at our institution. After
      the renal mass excision, biologic hemostatics such as FLOSEALTM and TISSEELTM
      (both from Baxter Healthcare Corp., Deerfield, IL) were used, and the perirenal
      fat and Gerota's fascia were sutured for reapproximation. RESULTS: All 24
      consecutive patients underwent OCNR-LPN successfully. The warm ischemic time for
      all cases was 0 minute. Thirteen patients were noted to have a low (4-6) RENAL
      nephrometry score (RNS), and 11 patients had a moderate (7-9) RNS. The mean tumor
      size among this cohort was 2.9 (range, 1.2-6.0) cm, and the mean estimated blood
      loss was 243 (range, 50-700) mL. The mean hospital stay was 6.9 (range, 5-10)
      days. The mean percentage of postoperative estimated glomerular filtration rate
      change increased by 0.9%. No positive surgical margins were noted, and 2 patients
      with Grade III complication by the Clavien-Dindo classification were treated by
      endoscopic or radiological intervention. CONCLUSIONS: OCNR-LPN with the perirenal
      fat and Gerota's fascia reapproximation technique is feasible. Our initial
      experience with OCNR-LPN demonstrates encouraging results of minimal renal
      function loss and complications.

PMID- 24742354
TI  - Self-excited oscillation of rotating double-walled carbon nanotubes.
AB  - The oscillatory behavior of a double-walled carbon nanotubes with a rotating
      inner tube is investigated using molecular dynamics simulation. In the
      simulation, one end of the outer tube is assumed to be fixed and the other is
      free. Without any prepullout of the rotating inner tube, it is interesting to
      observe that self-excited oscillation can be triggered by nonequilibrium
      attraction of the ends of two tubes. The oscillation amplitude increases until it
      reaches its maximum with decrease of the rotating speed of the inner tube. The
      oscillation of a bitube is sensitive to the gap between two walls. Numerical
      results also indicate that the zigzag/zigzag commensurate model with a larger gap
      of >0.335 nm can act as a terahertz oscillator, and the armchair/zigzag
      incommensurate model plays the role of a high amplitude oscillator with the
      frequency of 1 GHz. An oblique chiral model with a smaller gap of <0.335 nm is
      unsuitable for the oscillator because of the steep damping of oscillation. 

PMID- 24742353
TI  - What decides the suspicion of acute coronary syndrome in acute chest pain
      patients?
AB  - BACKGROUND: Physicians assessing chest pain patients in the emergency department
      (ED) base the likelihood of acute coronary syndrome (ACS) mainly on ECG, symptom
      history and blood markers of myocardial injury. Among these, the ECG has been
      stated to be the most important diagnostic tool. We aimed to analyze the relative
      contributions of these three diagnostic modalities to the ED physicians'
      evaluation of ACS likelihood in clinical practice. METHODS: 1151 consecutive ED
      chest pain patients were prospectively included. The ED physician's subjective
      assessment of the patient's likelihood of ACS (obvious ACS, strong, vague or no
      suspicion of ACS), the symptoms and the ECG were recorded on a special form. The
      ED TnT value was retrieved from the medical records. Frequency tables and
      logistic regression models were used to evaluate the contributions of the
      diagnostic tests to the level of ACS suspicion. RESULTS: Symptoms determined
      whether the physician had any suspicion of ACS (odds ratio, OR 526 for symptoms
      typical compared to not suspicious of ACS) since neither ECG nor TnT contributed
      significantly (ORs not significantly different from 1) to this assessment. ACS
      was suspected in only one in ten patients with symptoms not suspicious of ACS.
      Symptoms were also more important (OR 620 for typical symptoms) than ECG (OR 31
      for ischemic ECG) and TnT (OR 3.4 for a positive TnT) for the assessment of
      obvious ACS/strong suspicion versus vague/no suspicion. Of the patients with ST
      elevation on ECG, 71% were considered to have an obvious ACS, as opposed to only
      6% of those with symptoms typical of ACS and 10% of those with a positive TnT.
      CONCLUSION: The ED physicians used symptoms as the most important assessment tool
      and applied primarily the symptoms to determine the level of ACS suspicion and to
      rule out ACS. The ECG was primarily used to rule in ACS. The TnT level played a
      minor role for the assessment of ACS likelihood. Further studies regarding ACS
      prediction based on symptoms may help improve decision-making in ED patients with
      possible ACS.

PMID- 24742355
TI  - Raman spectroscopic study of antioxidant pigments from cup corals Tubastraea spp.
AB  - Chemical investigation of nonindigenous Tubastraea coccinea and T. tagusensis by
      Raman spectroscopy resulted in the identification of carotenoids and indolic
      alkaloids. Comparison of Raman data obtained for the in situ and crude extracts
      has shown the potential of the technique for characterizing samples which are
      metabolic fingerprints, by means of band analysis. Raman bands at ca. 1520, 1160,
      and 1005 cm(-1) assigned to nu1(C?C), nu2(C-C), and rho3(C-CH3) modes were
      attributed to astaxanthin, and the band at 1665 cm(-1) could be assigned to the
      nu(C-N), nu(C-O), and nu(C-C) coupled mode of the iminoimidazolinone from
      aplysinopsin. The antioxidant activity of the crude extracts has also been
      demonstrated, suggesting a possible role of these classes of compounds in the
      studied corals. 

PMID- 24742356
TI  - One-dimensional silicone nanofilaments.
AB  - A decade ago one-dimensional silicone nanofilaments (1D-SNF) such as fibres and
      wires were described for the first time. Since then, the exploration of 1D-SNF
      has led to remarkable advancements with respect to material science and surface
      science: one-, two- and three-dimensional nanostructures of silicone were unknown
      before. The discovery of silicone nanostructures marks a turning point in the
      research on the silicone material at the nanoscale. Coatings made of 1D-SNF are
      among the most superhydrophobic surfaces known today. They are free of fluorine,
      can be applied to a large range of technologically important materials and their
      properties can be modified chemically. This opens the way to many interesting
      applications such as water harvesting, superoleophobicity, separation of oil and
      water, patterned wettability and storage and manipulation of data on a surface.
      Because of their high surface area, coatings consisting of 1D-SNF are used for
      protein adsorption experiments and as carrier systems for catalytically active
      nanoparticles. This paper reviews the current knowledge relating to the broad
      development of 1D-SNF technologies. Common preparation and coating techniques are
      presented along with a comparison and discussion of the published coating
      parameters to provide an insight on how these affect the topography of the 1D-SNF
      or coating. The proposed mechanisms of growth are presented, and their potentials
      and shortcomings are discussed. We introduce all explored applications and
      finally identify future prospects and potentials of 1D-SNF with respect to
      applications in material science and surface science. 

PMID- 24742358
TI  - An examination of the frequency of invalid forgetting on the Test of Memory
      Malingering.
AB  - The Test of Memory Malingering (TOMM) is the most used performance validity test
      in neuropsychology, but does not measure response consistency, which is central
      in the measurement of credible presentation. Gunner, Miele, Lynch, and McCaffrey
      (2012) developed the Albany Consistency Index (ACI) to address this need. The ACI
      consistency measurement, however, may penalize examinees, resulting in suboptimal
      accuracy. The Invalid Forgetting Frequency Index (IFFI), created for the present
      study, utilizes an algorithm to identify and differentiate learning and
      inconsistent response patterns across TOMM trials. The purpose of this study was
      to assess the diagnostic accuracy of the ACI and IFFI against a reference test
      (Malingered Neurocognitive Dysfunction criteria), and to compare both to the
      standard TOMM indexes. This retrospective case-control study used 59 forensic
      cases from an outpatient clinic in Southern Kansas. Results indicated that
      sensitivity, negative predictive value, and overall accuracy of the IFFI were
      superior to both the TOMM indexes and ACI. Logistic regression odds ratios were
      similar for TOMM Trial 2, Retention, and IFFI (1.25, 1.24, 1.25, respectively),
      with the ACI somewhat lower (1.18). The IFFI had the highest rate of group
      membership predictions (79.7%). Implications and limitations of the present study
      are discussed.

PMID- 24742357
TI  - Ca2+-regulated secretory granule exocytosis in pancreatic and parotid acinar
      cells.
AB  - Protein secretion from acinar cells of the pancreas and parotid glands is
      controlled by G-protein coupled receptor activation and generation of the
      cellular messengers Ca(2+), diacylglycerol and cAMP. Secretory granule (SG)
      exocytosis shares some common characteristics with nerve, neuroendocrine and
      endocrine cells which are regulated mainly by elevated cell Ca(2+). However, in
      addition to diverse signaling pathways, acinar cells have large ~1 MUm diameter
      SGs (~30 fold larger diameter than synaptic vesicles), respond to stimulation at
      slower rates (seconds versus milliseconds), demonstrate significant constitutive
      secretion, and in isolated acini, undergo sequential compound SG-SG exocytosis at
      the apical membrane. Exocytosis proceeds as an initial rapid phase that peaks and
      declines over 3 min followed by a prolonged phase that decays to near basal
      levels over 20-30 min. Studies indicate the early phase is triggered by Ca(2+)
      and involves the SG proteins VAMP2 (vesicle associated membrane protein2), Ca(2+)
      sensing protein synatotagmin 1 (syt1) and the accessory protein complexin 2. The
      molecular details for regulation of VAMP8-mediated SG exocytosis and the
      prolonged phase of secretion are still emerging. Here we review the known
      regulatory molecules that impact the sequential exocytic process of SG tethering,
      docking, priming and fusion in acinar cells.

PMID- 24742359
TI  - Comparison of the Canadian CT head rule and the new orleans criteria in patients
      with minor head injury.
AB  - AIM: The aim of the study was to compare the New Orleans Criteria and the New
      Orleans Criteria according to their diagnostic performance in patients with mild
      head injury. METHODS: The study was designed and conducted prospectively after
      obtaining ethics committee approval. Data was collected prospectively for
      patients presenting to the ED with Minor Head Injury. After clinical assessment,
      a standard CT scan of the head was performed in patients having at least one of
      the risk factors stated in one of the two clinical decision rules. Patients with
      positive traumatic head injury according to BT results defined as Group 1 and
      those who had no intracranial injury defined as Group 2. Statistical analysis was
      performed with SPSS 11.00 for Windows. ROC analyze was performed to determine the
      effectiveness of detecting intracranial injury with both decision rules. p < 0.05
      was considered statistically significant. RESULTS: 175 patients enrolled the
      study. Male to female ratio was 1.5. The mean age of the patients was 45 +/- 21,3
      in group 1 and 49 +/- 20,6 in group 2. The most common mechanism of trauma was
      falling. The sensitivity and specificity of CCHR were respectively 76.4% and
      41.7%, whereas sensitivity and specificity of NOC were 88.2% and 6.9%.
      CONCLUSION: The CCHR has higher specificity, PPV and NPV for important clinical
      outcomes than does the NOC.

PMID- 24742360
TI  - Mercury stable isotopic compositions in coals from major coal producing fields in
      China and their geochemical and environmental implications.
AB  - Total mercury (Hg) concentrations (THg) and stable mercury isotopic compositions
      were measured in coal samples (n = 61) from major coal producing fields in China.
      The THg concentrations in coals ranged from 0.05 to 0.78 MUg g(-1), with a
      geometric mean of 0.22 MUg g(-1). Hg isotopic compositions in coals showed large
      variations both in mass-dependent fractionation (MDF, delta(202)Hg: -2.36 to 
      0.140/00) and mass-independent fractionation (MIF, Delta(199)Hg: -0.44 to
      +0.380/00). The MIF signatures in coals may reveal important information on the
      coal-forming conditions (e.g., humic and sapropelic). The
      Delta(199)Hg/Delta(201)Hg of ~1 determined in coals indicated that a portion of
      Hg has been subjected to photoreduction process prior to being incorporated to
      coals. On the basis of THg, Hg isotopic signatures, and other geological factors
      (e.g., total ash content and total sulfur content), the potential sources of Hg
      in coals from different coal producing regions were estimated. The main source of
      Hg in coals from southwestern China and eastern part of northern China is likely
      geogenic Hg, whereas the source of Hg in coals from other parts of northern China
      is mainly biogenic Hg. Finally, we estimated that Hg emission from coal
      combustion in China is characterized by diagnostic Hg isotopic signatures
      (delta(202)Hg: ~-0.700/00 and Delta(199)Hg: ~-0.050/00). The present study
      demonstrates that Hg isotopes can serve as a tool in understanding the sources
      and transformation of Hg in coals and may also be used as a tracer to quantify Hg
      emissions from coal combustion. 

PMID- 24742362
TI  - This is your brain on calcium: psychosis as the presentation of isolated
      hypoparathyroidism.

PMID- 24742361
TI  - Orchestrated increase of dopamine and PARK mRNAs but not miR-133b in dopamine
      neurons in Parkinson's disease.
AB  - Progressive loss of substantia nigra dopamine neurons (SN DA) is a hallmark of
      aging and of Parkinson's disease (PD). Mutations in PARK genes cause familial PD
      forms. Increased expression of alpha-synuclein (PARK4) is a disease-triggering
      event in familial PD and also observed in SN DA neurons in sporadic PD but
      related transcriptional changes are unknown. With optimized single-cell
      quantitative real-time polymerase chain reaction analysis, we compared messenger
      RNA and microRNA levels in SN DA neurons from sporadic PD patients and controls.
      Non-optimally matched donor ages and RNA integrities are common problems when
      analyzing human samples. We dissected the influence of distinct ages and RNA
      integrities of our samples by applying a specifically-optimized, linear-mixed
      effects model to quantitative real-time polymerase chain reaction-data. We
      identified that elevated alpha-synuclein messenger RNA levels in SN DA neurons of
      human PD brains were positively correlated with corresponding elevated levels of
      mRNAs for functional compensation of progressive SN DA loss and for enhanced
      proteasomal (PARK5/UCHL1) and lysosomal (PARK9/ATPase13A2) function, possibly
      counteracting alpha-synuclein toxicity. In contrast, microRNA miR-133b levels,
      previously implicated in transcriptional dysregulation in PD, were not altered in
      SN DA neurons in PD. 

PMID- 24742363
TI  - Soluble receptor of advanced glycation end-products and endothelial dysfunction
      in COPD.
AB  - BACKGROUND: Chronic obstructive pulmonary disease (COPD) is accompanied by an
      increased cardiovascular risk which is aggravated by the incidence of acute
      exacerbations (AE). Endothelial function, as well as the soluble receptor for
      advanced glycation end-products (sRAGE), both markers of cardiovascular risk, has
      been shown to be decreased in stable COPD. OBJECTIVES: We aimed to investigate a
      possible link between sRAGE and endothelial function in AE of COPD. We
      hypothesize that circulating levels of sRAGE and endothelial function are
      impaired during AE and improve after clinical recovery, respectively. METHODS: We
      enrolled patients admitted to hospital due to an AE of COPD without overt
      cardiovascular comorbidities. Study related procedures comprised spirometry,
      measurement of plasma sRAGE levels and the quantification of endothelial function
      by means of the flow-mediated dilation technique (FMD). All measurements were
      scheduled during hospitalization and after confirmed clinical stability. RESULTS:
      We recruited 29 patients (27% female) with moderate to severe COPD. Median sRAGE
      concentration was 525 pg/mL (371-770, 1st-3rd quartile) and mean FMD 6.7 +/- 3.6%
      at AE. There was a significant increase of sRAGE levels to 876 pg/mL (633-1371,
      1st-3rd quartile, p < 0.001) and a simultaneous improvement in FMD (10.0 +/-
      3.4%, p < 0.001) after clinical recovery. There was a significant positive
      association between sRAGE and FMD (regression coefficient = 2.43; p = 0.01) in
      our study sample. CONCLUSION: Our results indicate a substantial decrease in
      sRAGE levels and endothelial function during AE, with evidence of improvements
      after clinical recovery. sRAGE may contribute to cardiovascular risk in COPD.

PMID- 24742364
TI  - Oral iodinated activated charcoal improves lung function in patients with COPD.
AB  - The effect of 8 weeks treatment with oral iodinated activated charcoal (IAC) on
      lung function of patients with moderate chronic obstructive pulmonary disease
      (COPD) was examined in a double blind randomized placebo controlled parallel
      group study with 40 patients. In the IAC group, patients showed a statistically
      significant improvement of FEV1 baseline by 130 ml compared to placebo,
      corresponding to 8.2% improvement (p = 0.031*). Correlation statistics revealed
      that the improvement of FEV1 baseline was significantly correlated both to FEV1
      post-bronchodilator (p = 0.0020**) and FEV1 post-exercise (0.033*) values. This
      demonstrates that the improved baseline lung function by IAC did not inhibit a
      further beta2-adrenoceptor relaxation, and thus that patients did not reach a
      limit for maximal improvement of the lung function after IAC treatment. Eight
      patients in the IAC group developed abnormal thyroid hormone levels transiently
      during the treatment. This side effect was not correlated to improvement of lung
      function (p = 0.82). No serious adverse effects directly related to the treatment
      were recorded. In summary, this study demonstrates that iodinated activated
      charcoal surprisingly and significantly improved lung function of patients with
      moderate COPD. The underlying mechanism of action is unclear, but is likely to be
      different from the drugs used today. The immediate conclusion is that further
      studies are now justified in order to determine clinical efficacy of IAC in COPD
      and explore possible mechanisms of action.

PMID- 24742365
TI  - MALDI imaging analysis of neuropeptides in the Africanized honeybee (Apis
      mellifera) brain: effect of ontogeny.
AB  - The occurrence and spatial distribution of the neuropeptides AmTRP-5 and AST-1 in
      the honeybee brain were monitored via MALDI spectral imaging according to the
      ontogeny of Africanized Apis mellifera. The levels of these peptides increased in
      the brains of 0-15 day old honeybees, and this increase was accompanied by an
      increase in the number of in-hive activities performed by the nurse bees,
      followed by a decrease in the period from 15 to 25 days of age, in which the
      workers began to perform activities outside the nest (guarding and foraging). The
      results obtained in the present investigation suggest that AmTRP-5 acts in the
      upper region of both pedunculi of young workers, possibly regulating the cell
      cleaning and brood capping activities. Meanwhile, the localized occurrence of
      AmTRP-5 and AST-1 in the antennal lobes, subesophageal ganglion, upper region of
      the medulla, both lobula, and alpha- and beta-lobes of both brain hemispheres in
      20 to 25 day old workers suggest that the action of both neuropeptides in these
      regions may be related to their localized actions in these regions, regulating
      foraging and guarding activities. Thus, these neuropeptides appear to have some
      functions in the honeybee brain that are specifically related to the age-related
      division of labor. 

PMID- 24742367
TI  - Menopause-specific quality of life of a group of urban women, West Bengal, India.
AB  - OBJECTIVE: To find out the association of menopause-specific quality of life of
      women with menopausal status. METHODS: In this cross-sectional study, we involved
      250 Bengali-speaking women of Hindu ethnic group (118 perimenopausal and 132
      postmenopausal), aged 40-65 years from urban areas of North 24 Paraganas, a
      district of West Bengal, India. The Menopause-Specific Quality of Life
      questionnaire (MENQOL) consisting of 29 menopausal symptoms, grouped under four
      menopausal domains (vasomotor, psychosocial, physical and sexual), was used to
      assess menopause-specific quality of life. Scores of four menopausal domains
      generated a composite score of 'Quality of Life'. Additionally, participants were
      also interviewed for their sociodemographic characteristics. RESULTS: Bivariate
      analyses showed significant difference in all the domains of menopause-specific
      quality of life (barring vasomotor domain) when compared for menopausal status.
      Results of ANCOVA showed that menopausal status was significantly associated only
      with the physical domain after removing the effects of sociodemographic
      characteristics. CONCLUSION: Menopausal status had a significant association with
      the physical domain of menopause-specific quality of life of women.

PMID- 24742366
TI  - Identification of inhibitors of inositol 5-phosphatases through multiple
      screening strategies.
AB  - Phosphoinositides are low abundance membrane phospholipids that have key roles in
      signaling, membrane trafficking, and cytoskeletal dynamics in all cells. Until
      recently, strategies for robust and quantitative development of pharmacological
      tools for manipulating phosphoinositide levels have focused selectively on
      PI(3,4,5)P3 due to the importance of this lipid in growth factor signaling and
      cell proliferation. However, drugs that affect levels of other phosphoinositides
      have potential therapeutic applications and will be powerful research tools.
      Here, we describe methodology for the high-throughput screening of small molecule
      modulators of the inositol 5-phosphatases, which dephosphorylate PI(4,5)P2 (the
      precursor for PI(3,4,5)P3) and PI(3,4,5)P3). We developed three complementary in
      vitro activity assays, tested hit compounds on a panel of 5-phosphatases, and
      monitored efficacy toward various substrates. Two prominent chemical scaffolds
      were identified with high nanomolar/low micromolar activity, with one class
      showing inhibitory activity toward all 5-phosphatases tested and the other
      selective activity toward OCRL and INPP5B, which are closely related to each
      other. One highly soluble OCRL/INPP5B-specific inhibitor shows a direct
      interaction with the catalytic domain of INPP5B. The efficacy of this compound in
      living cells was validated through its property to enhance actin nucleation at
      the cell cortex, a PI(4,5)P2 dependent process, and to inhibit PI(4,5)P2
      dephosphorylation by OCRL (both overexpressed and endogenous enzyme). The assays
      and screening strategies described here are applicable to other phosphoinositide
      metabolizing enzymes, at least several of which have major clinical relevance.
      Most importantly, this study identifies the first OCRL/INPP5B specific inhibitor
      and provides a platform for the design of more potent inhibitors of this family
      of enzymes.

PMID- 24742368
TI  - Asynchronous transcriptional silencing of individual retroviral genomes in
      embryonic cells.
AB  - BACKGROUND: Retroviral DNAs are profoundly silenced at the transcriptional level
      in embryonic cell types. The transcriptional profile of pluripotent stem cells
      has been demonstrated to be extremely heterogeneous from cell to cell, and how
      the silencing of retroviral DNAs is achieved is not yet well characterized.
      RESULTS: In the current study, we investigated the transcriptional silencing
      dynamics in stem cells by independently monitoring the expression of two Moloney
      murine leukemia virus (MMLV) retroviral vectors newly introduced into embryonic
      carcinoma (EC) cells. Although MMLV is efficiently silenced by epigenetic
      mechanisms in most such cells, a small number of the doubly-transduced EC cells
      transiently show double-positive proviral expression. These cells were sorted and
      their expression patterns were studied over time as silencing is established.
      CONCLUSIONS: Our data suggest that retroviral silencing occurs stochastically, in
      an individual locus-specific fashion, and often without synchronous silencing of
      both viruses in the same cells. Surprisingly, the chromatin modifications that
      mark the silenced proviruses are unchanged even in cells that temporarily escape
      silencing. This local silencing effect is a feature of stem cell epigenomic
      regulation that has not previously been revealed.

PMID- 24742369
TI  - Analysis of eicosanoids by LC-MS/MS and GC-MS/MS: a historical retrospect and a
      discussion.
AB  - Eicosanoids are a large family that derives from arachidonic acid, i.e.,
      eicosatetraenoic acid. Prominent members include prostaglandins, thromboxane and
      leukotrienes. They are biologically highly active lipid mediators and play
      multiple physiological roles. GC-MS/MS has played a pivotal role in the
      identification and quantification of eicosanoids in biological samples. This
      technology generated a solid knowledge of their analytical chemistry,
      biochemistry, physiology and pharmacology. Since about a decade, GC-MS and GC
      MS/MS are increasingly displaced by the seemingly more simple, rapid and powerful
      LC-MS/MS in the area of instrumental analysis of physiological substances, drugs
      and their metabolites. In this article, we review and discuss LC-MS/MS methods
      published over the last decade from the perspective of the GC-MS/MS user. Our
      analysis revealed that the shift from the adult GC-MS/MS to the youthful emerging
      LC-MS/MS technology in eicosanoid analysis is associated with several important
      challenges. Known pitfalls and problematic issues discovered by eicosanoid
      pioneers by using GC-MS/MS are often ignored by LC-MS/MS users. Established
      reference values and intervals provided by GC-MS-based methods are not considered
      properly in developing and validating LC-MS/MS methods. Virtually, there is a
      belief in the unlimited capability of the LC-MS/MS technique in eicosanoid
      analysis, a thought that simulates analytical certainty. LC-MS/MS users should
      profit from the plethora of solid knowledge acquired from the use of GC-MS/MS in
      eicosanoid analysis in basic and clinical research. 

PMID- 24742370
TI  - Motor and non-motor features of Parkinson's disease that predict persistent drug
      induced Parkinsonism.
AB  - BACKGROUND: Drug-induced Parkinsonism is common, causes significant morbidity,
      and can be clinically indistinguishable from idiopathic Parkinson's disease.
      Additionally, drug-induced Parkinsonism may, in some cases, represent "unmasking"
      of incipient Parkinson's disease. Clinical features or tests that distinguish
      degenerative from pharmacologic Parkinsonism are needed. METHODS: We performed a
      retrospective case-control study of 97 drug-induced Parkinsonism subjects and 97
      age-matched patients with Parkinson's disease. We compared the frequency of
      subjective motor and non-motor complaints, objective motor findings (Unified
      Parkinson's Disease Rating Scale Part III) and, where available, objective
      olfactory tests. We also performed a nested case-control study wherein we
      compared these same features between drug-induced Parkinsonism patients based on
      whether or not they recovered after changing the offending agent. RESULTS: Non
      motor symptoms including constipation and sexual dysfunction were more common in
      Parkinson's disease than in drug-induced Parkinsonism. While total motor scores
      were similar between groups, Postural Instability-Gait Difficulty scores were
      also higher in Parkinson's disease. Features that were significantly different or
      showed a trend towards significance in both comparisons included subjective loss
      of facial expression, dream-enactment behavior, autonomic complaints and Postural
      Instability-Gait Difficulty scores. Hyposmia was more common in Parkinson's
      disease and was strongly predictive of persistent drug-induced Parkinsonism after
      therapy change (odds ratio 30.3, 95% confidence interval: 1.5-500, p = 0.03).
      CONCLUSIONS: A constellation of motor and non-motor features may differentiate
      unmasked Parkinson's disease from drug-induced Parkinsonism. In particular,
      olfactory testing may offer a simple and inexpensive method to help predict
      outcomes in drug-induced Parkinsonism and, potentially, identify a cohort of pre
      motor Parkinson's disease.

PMID- 24742371
TI  - Robot-assisted neck dissection via a transaxillary and retroauricular approach
      versus a conventional transcervical approach in papillary thyroid cancer with
      cervical lymph node metastases.
AB  - BACKGROUND: Recently, robot-assisted neck dissection (ND) using a transaxillary
      approach in thyroid cancer patients with lateral neck metastases (LNM) was
      demonstrated to be feasible. The aim of this study was to compare the surgical
      outcomes of a modified transaxillary and retroauricular (TARA) versus a
      conventional transcervical approach in papillary thyroid carcinoma (PTC) patients
      with LNM. PATIENTS AND METHODS: In total, 47 patients with PTC underwent total
      thyroidectomy with central compartment ND and modified radical ND except Level I.
      Twenty-two NDs were performed via the TARA approach, and 25 unilateral NDs were
      performed via the conventional transcervical approach. RESULTS: The TARA and the
      open ND groups consisted of 22 and 25 patients, respectively. The operation time
      for ND in the TARA group was longer than that in the open ND group (209.4+/-38.2
      minutes versus 143.1+/-30.5 minutes; P=.000). The mean scar satisfaction score in
      the TARA group was higher than in the conventional ND group (3.9+/-1.0 versus
      2.8+/-1.0; P=.000). There were no differences in the mean number of retrieved
      lymph nodes. CONCLUSIONS: The robot-assisted ND via the TARA approach can be an
      alternative option that produces excellent esthetic results for the management of
      LNM in PTC patients.

PMID- 24742372
TI  - Origin of ion selectivity in Phaseolus coccineus mitochondrial VDAC.
AB  - The mitochondrial voltage-dependent a nion-selective channel (VDAC) is the major
      permeation pathway for small ions and metabolites. Although a wealth of
      electrophysiological data has been obtained on different VDAC species, the
      physical mechanisms of their ionic selectivity are still elusive. We addressed
      this issue using electrophysiological experiments performed on plant VDAC. A
      simple macroscopic electrodiffusion model accounting for ion diffusion and for an
      effective fixed charge of the channel describes well its selectivity. Brownian
      Dynamics simulations of ion permeation performed on plant and mammalian VDACs
      point to the role of specific charged residues located at about the middle of the
      pore. 

PMID- 24742373
TI  - Ultrasound Detection of Myocardial Ischemic Memory Using an E-Selectin Targeting
      Peptide Amenable to Human Application.
AB  - Vascular endothelial leukocyte adhesion molecules, such as E-selectin, are
      acutely upregulated in myocardial ischemia/reperfusion and are thus "ischemic
      memory" biomarkers for recent cardiac ischemia. We sought to develop an
      ultrasound molecular imaging agent composed of microbubbles (MBs) targeted to E
      selectin to enable the differential diagnosis of myocardial ischemia in patients
      presenting with chest pain of unclear etiology. Biodegradable polymer MBs were
      prepared bearing a peptide with specific human E-selectin affinity (MBESEL).
      Control MBs had scrambled peptide (MBCTL) or nonspecific IgG (MBIgG). MBESEL
      adhesion to activated rat endothelial cells (ECs) was confirmed in vitro in a
      flow system and in vivo with intravital microscopy of rat cremaster
      microcirculation. Ultrasound molecular imaging of recent myocardial ischemia was
      performed in rats 4 hours after transient (15 minutes) coronary occlusion. MBESEL
      adhesion was higher to inflamed versus normal ECs in vitro; there was no
      difference in MBCTL or MBIgG adhesion to inflamed versus normal ECs. There was
      greater adhesion of MBESEL to inflamed versus noninflamed microcirculation and
      minimal adhesion of MBCTL or MBIgG under any condition. Ultrasound imaging after
      injection of MBSEL demonstrated persistent contrast enhancement of the previously
      ischemic region. Videointensity in postischemic myocardium after MBESEL was
      higher than that in the nonischemic bed (11.6 +/- 2.7 dB vs 3.6 +/- 0.8 dB, p <
      .02) and higher than that after MBCTL (4.0 +/- 1.0 dB, p < .03) or MBIgG (1.7 +/-
      0.1 dB, p < .03). MBs targeted to E-selectin via a short synthetic peptide with
      human E-selectin binding affinity enables echocardiographic detection of recent
      ischemia, setting the stage for clinical myocardial ischemic memory imaging to
      identify acute coronary syndromes.

PMID- 24742375
TI  - Nanopillar spin filter tunnel junctions with manganite barriers.
AB  - The potential of a manganite ferromagnetic insulator in the field of spin
      filtering has been demonstrated. For this, an ultrathin film of Sm0.75Sr0.25MnO3
      is integrated as a barrier in an epitaxial oxide nanopillar tunnel junction and a
      high spin polarization of up to 75% at 5 K has been achieved. A large zero-bias
      anomaly observed in the dynamic conductance at low temperatures is explained in
      terms of the Kondo scattering model. In addition, a decrease in spin polarization
      at low bias and hysteretic magneto-resistance at low temperatures are reported.
      The results open up new possibilities for spin-electronics and suggest
      exploration of other manganites-based materials for the room temperature spin
      filter applications. 

PMID- 24742374
TI  - RasG signaling is important for optimal folate chemotaxis in Dictyostelium.
AB  - BACKGROUND: Signaling pathways linking receptor activation to actin
      reorganization and pseudopod dynamics during chemotaxis are arranged in complex
      networks. Dictyostelium discoideum has proven to be an excellent model system for
      studying these networks and a body of evidence has indicated that RasG and RasC,
      members of the Ras GTPase subfamily function as key chemotaxis regulators.
      However, recent evidence has been presented indicating that Ras signaling is not
      important for Dictyostelium chemotaxis. In this study, we have reexamined the
      role of Ras proteins in folate chemotaxis and then, having re-established the
      importance of Ras for this process, identified the parts of the RasG protein
      molecule that are involved. RESULTS: A direct comparison of folate chemotaxis
      methodologies revealed that rasG-C- cells grown in association with a bacterial
      food source were capable of positive chemotaxis, only when their initial position
      was comparatively close to the folate source. In contrast, cells grown in axenic
      medium orientate randomly regardless of their distance to the micropipette.
      Folate chemotaxis is restored in rasG-C- cells by exogenous expression of protein
      chimeras containing either N- or C- terminal halves of the RasG protein.
      CONCLUSIONS: Conflicting data regarding the importance of Ras to Dictyostelium
      chemotaxis were the result of differing experimental methodologies. Both axenic
      and bacterially grown cells require RasG for optimal folate chemotaxis,
      particularly in weak gradients. In strong gradients, the requirement for RasG is
      relaxed, but only in bacterially grown cells. Both N- and C- terminal portions of
      the RasG protein are important for folate chemotaxis, suggesting that there are
      functionally important amino acids outside the well established switch I and
      switch II interaction surfaces.

PMID- 24742376
TI  - Septal serotonin depletion in rats facilitates working memory in the radial arm
      maze and increases hippocampal high-frequency theta activity.
AB  - Hippocampal theta activity, which is strongly modulated by the septal
      medial/Broca's diagonal band neurons, has been linked to information processing
      of the hippocampus. Serotonin from the medial raphe nuclei desynchronises
      hippocampal theta activity, whereas inactivation or a lesion of this nucleus
      induces continuous and persistent theta activity in the hippocampus. Hippocampal
      serotonin depletion produces an increased expression of high-frequency theta
      activity concurrent with the facilitation of place learning in the Morris maze.
      The medial septum-diagonal band of Broca complex (MS/DBB) has been proposed as a
      key structure in the serotonin modulation of theta activity. We addressed whether
      serotonin depletion of the MS/DBB induces changes in the characteristics of
      hippocampal theta activity and whether the depletion is associated with learning
      in a working memory spatial task in the radial arm maze. Sprague Dawley rats were
      depleted of 5HT with the infusion of 5,7-dihydroxytriptamine (5,7-DHT) in MS/DBB
      and were subsequently trained in the standard test (win-shift) in the radial arm,
      while the CA1 EEG activity was simultaneously recorded through telemetry. The
      MS/DBB serotonin depletion induced a low level of expression of low-frequency
      (4.5-6.5Hz) and a higher expression of high-frequency (6.5-9.5Hz) theta activity
      concomitant to a minor number of errors committed by rats on the working memory
      test. Thus, the depletion of serotonin in the MS/DBB caused a facilitator effect
      on working memory and a predominance of high-frequency theta activity. 

PMID- 24742377
TI  - Reversal of myofibroblast differentiation: a review.
AB  - It has long been considered that fibrosis and fibroblast-to-myofibroblast
      differentiation are irreversible processes. However, recent data obtained
      indicates that tissue fibrosis and fibroblast-to-myofibroblast differentiation
      can indeed be reversed, which offers the possibility of a new therapeutic
      approach for fibrotic disorders. Here, we discuss the origin of the
      myofibroblasts and different aspects of their differentiation, especially the key
      mediators and TGFbeta-induced signaling pathways. We also report here a few
      factors involved in myofiroblast dedifferentiation and several compounds which
      can reverse the established dedifferentiated myofibroblast, as examples that
      provide the reader a glimpse of the current trends of approach for discovering
      useful anti-fibrotic drugs. 

PMID- 24742378
TI  - Isodeoxyelephantopin from Elephantopus scaber (Didancao) induces cell cycle
      arrest and caspase-3-mediated apoptosis in breast carcinoma T47D cells and lung
      carcinoma A549 cells.
AB  - BACKGROUND: Isodeoxyelephantopin (IDOE) isolated from Elephantopus scaber L.
      (Didancao) is used in Chinese medicine for the treatment of some types of cancer.
      The anti-cancer mechanism of IDOE remains unclear. This study aims to investigate
      the antiproliferative activity of IDOE on breast carcinoma T47D cells and lung
      carcinoma A549 cells. METHODS: The growth inhibitory effects of IDOE on breast
      carcinoma T47D cells, lung carcinoma A549 cells, and normal lymphocytes were
      evaluated by the MTT assay. Morphological analysis of apoptosis induction was
      performed by acridine orange/ethidium bromide dual-staining and Hoechst 33342
      nuclear staining. The cell cycle profile, caspase-3 expression, and annexin V
      staining were evaluated by flow cytometry. RESULTS: IDOE inhibited the growth of
      A549 and T47D cells in a dose- and time-dependent manner with IC50 values of
      10.46 and 1.3 MUg/mL, respectively. IDOE was not significantly toxic to normal
      lymphocytes. The cells became detached from the monolayer and rounded up, had
      fragmented nuclei and condensed chromatin, and the numbers of apoptotic cells
      increased (P = 0.0003). IDOE-induced cell death was associated with activated
      caspase-3 expression followed by cell cycle arrest at G2/M phase. CONCLUSIONS:
      IDOE inhibited the proliferation of breast cancer cells and lung carcinoma cells
      and induced caspase-3-mediated apoptosis and cell cycle arrest in the treated
      cells.

PMID- 24742379
TI  - Diosgenin interferes coronary vasoconstriction and inhibits osteochondrogenic
      transdifferentiation of aortic VSMC in CRF rats.
AB  - Cardiovascular dysfunction and vascular calcification is the leading cause of
      death in chronic renal failure (CRF) patients. This study was designed to
      evaluate the effect of diosgenin on coronary flow resistance and to address the
      question whether the previously proven antivascular calcification potential of
      diosgenin is associated or not with the osteochondrogenic transdifferentiation of
      vascular smooth muscle cells (VSMC). In this study, CRF in Wistar rats was
      induced by fed with 0.75% adenine and diosgenin was treated everyday at the dose
      of 40 mg/kg. Langendorff based isolated heart protocol was employed to analyze
      the coronary flow resistance. Western blot method was used to explore the
      phosphorylation dynamics of endothelial nitric oxide synthase (eNOS) at the
      serine 1177 residue. In addition, cardiac nitric oxide metabolites level also
      assessed. Quantitative expression of VSMC and osteochondrogenic markers was also
      evaluated. Antioxidant potential of diosgenin was studied in vitro. The outcome
      of the present study explores that diosgenin treatment significantly improves the
      coronary resistance and increased the nitric oxide metabolites level compared
      with CRF. Further, diosgenin increases the phosphorylation of eNOS (peNOS
      ser1177). Moreover, diosgenin reduced the aortic expression of osteochondrogenic
      markers and improved the VSMC phenotype components. Further, diosgenin shows
      concentration dependent antioxidant potential. In conclusion, this study have
      proven that diosgenin have enough potential to improve the coronary function and
      interfere the osteochondrogenic transdifferentiation program of aortic VSMC which
      supports its antivascular calcification potential.

PMID- 24742380
TI  - Glutathione modulation during sensitization as well as challenge phase regulates
      airway reactivity and inflammation in mouse model of allergic asthma.
AB  - Glutathione, being a major intracellular redox regulator has been shown to be
      implicated in regulation of airway reactivity and inflammation. However, no study
      so far has investigated the effect of glutathione depletion/repletion during
      sensitization and challenge phases separately, which could provide an important
      insight into the pathophysiology of allergic asthma. The aim of the present study
      was to evaluate the role of glutathione depletion/repletion during sensitization
      and challenge phases separately in a mouse model of allergic asthma. Buthionine
      sulphoximine (BSO), an inhibitor of gamma-glutamylcysteine synthetase or N-acetyl
      cysteine (NAC), a thiol donor were used for depletion or repletion of glutathione
      levels respectively during both sensitization and challenge phases separately
      followed by assessment of airway reactivity, inflammation and oxidant-antioxidant
      balance in allergic mice. Depletion of glutathione with BSO during sensitization
      as well as challenge phase worsened allergen induced airway
      reactivity/inflammation and caused greater oxidant-antioxidant imbalance as
      reflected by increased NADPH oxidase expression/reactive oxygen species (ROS)
      generation/lipid peroxides formation and decreased total antioxidant capacity. On
      the other hand, repletion of glutathione pool by NAC during sensitization and
      challenge phases counteracted allergen induced airway reactivity/inflammation and
      restored oxidant-antioxidant balance through a decrease in NADPH oxidase
      expression/ROS generation/lipid peroxides formation and increase in total
      antioxidant capacity. Taken together, these findings suggest that depletion or
      repletion of glutathione exacerbates or ameliorates allergic asthma respectively
      by regulation of airway oxidant-antioxidant balance. This might have implications
      towards increased predisposition to allergy by glutathione depleting
      environmental pollutants. 

PMID- 24742381
TI  - Executive functioning in alcoholics following an mHealth cognitive stimulation
      program: randomized controlled trial.
AB  - BACKGROUND: The consequences of alcohol dependence are severe and may range from
      physical disease to neuropsychological deficits in several cognitive domains.
      Alcohol abuse has also been related to brain dysfunction specifically in the
      prefrontal cortex. Conventional neuropsychological interventions (paper-and
      pencil cognitive stimulation training) have a positive effect but are time
      consuming, costly, and not motivating for patients. OBJECTIVE: Our goal was to
      test the cognitive effects of a novel approach to neuropsychological
      intervention, using mobile technology and serious games, on patients with alcohol
      dependence. METHODS: The trial design consisted of a two-arm study assessing the
      cognitive outcomes of neuropsychological intervention with mobile serious games
      (mHealth) versus control (treatment-as-usual with no neuropsychological
      intervention) in patients undergoing treatment for alcohol dependence syndrome.
      Sixty-eight patients were recruited from an alcohol-rehab clinic and randomly
      assigned to the mHealth (n=33) or control condition (n=35). The intervention on
      the experimental group consisted of a therapist-assisted cognitive stimulation
      therapy for 4 weeks on a 2-3 days/week basis. RESULTS: Fourteen patients dropped
      out of the study. The results of the neuropsychological assessments with the
      remaining 54 patients showed an overall increase (P<.05) of general cognitive
      abilities, mental flexibility, psychomotor processing speed, and attentional
      ability in both experimental (n=26) and control groups (n=28). However, there was
      a more pronounced improvement (P=.01) specifically in frontal lobe functions from
      baseline (mean 13.89, SE 0.58) to follow-up (mean 15.50, SE 0.46) in the
      experimental group but not in the control group. CONCLUSIONS: The overall
      increase in general cognitive function for both experimental and control groups
      supports the beneficial role of existing alcohol treatment protocols aimed at
      minimizing withdrawal symptoms, but the differential improvements observed in
      frontal lobe functioning supports the use of mobile serious games for
      neuropsychological stimulation to overcome executive dysfunction in patients with
      alcohol dependence. This trial was negative on two neuropsychological/cognitive
      tests, and positive on one. TRIAL REGISTRATION: ClinicalTrials.gov NCT01942954;
      http://www.clinicaltrials.gov/ct2/show/NCT01942954.

PMID- 24742382
TI  - Inputs from the thalamocortical system on axon pathfinding mechanisms.
AB  - Our understanding of axon pathfinding mechanisms has dramatically advanced thanks
      to the identification of guidance cues and receptors, and has been forged by the
      study of a limited number of model systems. Thalamocortical axons, which are
      essential for sensory processing and neocortical functioning, convey sensory
      information to the neocortex through a tightly controlled topographical
      interconnectivity between distinct thalamic neurons and cortical areas. Recent
      studies on this projection have provided mechanistic insights onto integrated
      processes controlling brain wiring: axons/guidepost cells interactions, building
      of reciprocal connections and the combinatorial activity of guidance cues. This
      review provides a selective overview of these novel features and stresses the
      interest of thalamocortical axons as an emerging model for studying axonal
      guidance and plasticity. 

PMID- 24742383
TI  - Synthesis and antiproliferative activity of ligerin and new fumagillin analogs
      against osteosarcoma.
AB  - Ligerin (1) is a natural chlorinated merosesquiterpenoid related to fumagillin
      (2) exhibiting a selective antiproliferative activity against osteosarcoma cell
      lines and an in vivo antitumor activity in a murine model. Semisynthesis of
      ligerin analogs was performed in order to study the effects of the C3
      spiroepoxide substitution by a halogenated moiety together with the modulation of
      the C6 chain. Results showed that all derivatives exhibited an in vitro
      antiproliferative activity against osteosarcoma cell lines and that chlorohydrin
      compounds were equally or more active than their spiroepoxy analogs. Among
      semisynthetic analogs, the parent compound 1 was the best candidate for further
      studies since it exhibited higher or equivalent activity compared to TNP470 (3)
      against SaOS2 and MG63 human osteosarcoma cells with a four times weaker toxicity
      against HFF2 human fibroblasts. Quantitative videomicroscopy analysis was
      conducted and allowed a better understanding of the mechanism of its
      antiproliferative activity. 

PMID- 24742384
TI  - Influence of the adamantyl moiety on the activity of biphenylacrylohydroxamic
      acid-based HDAC inhibitors.
AB  - To investigate the influence of the adamantyl group on the biological properties
      of known HDAC inhibitors with a 4-phenylcinnamic skeleton, a series of compounds
      having the adamantyl moiety in the cap structure were synthesized and compared to
      the corresponding hydroxamic acids lacking this group. An unexpected finding was
      the substantial reduction of inhibitory activity toward the tested enzymes, in
      particular HDAC6, following the introduction of the adamantyl group. In spite of
      the reduced ability to function as HDAC inhibitors, the compounds containing the
      adamantyl moiety still retained a good efficacy as antiproliferative and
      proapoptotic agents. A selected compound (2c; ST3056) of this series exhibited an
      appreciable antitumor activity against the colon carcinoma xenograft HCT116. 

PMID- 24742385
TI  - Synthesis of novel building blocks of benzosuberone bearing coumarin moieties and
      their evaluation as potential anticancer agents.
AB  - A series of novel benzosuberone bearing coumarin moieties 5a-c have been
      synthesized and their structures were determined by analytical and spectral (FT
      IR, (1)H NMR, (13)C NMR, HRMS) studies. The newly synthesized compounds were
      evaluated for their cytotoxicity against four human cancer cell lines, A549
      (Human alveolar adenocarcinoma cell line), HeLa (Human cervical cancer cell
      line), MDA-MB-231 (Human breast adenocarcinoma cell line), MCF-7 (Human breast
      adenocarcinoma cell line) and normal cell line HEK293 (Human embryonic kidney
      cell line). Compound 5a exhibited promising cytotoxicity with IC50 values ranging
      from 3.35 to 16.79 MUM against all the cancer cell lines like A549, HeLa, MCF-7
      and MDA-MB-231, while compound 5c showed significant cytotoxicity against HeLa
      and MDA-MB-231 with IC50 values of 6.72 and 4.87, respectively. 

PMID- 24742389
TI  - Chemical biology: contribution to molecular therapeutic innovation--a new role
      for chemistry? Report from the thematic symposium organized by the SCT (French
      Medicinal Chemistry Society), November 26th, 2013.

PMID- 24742390
TI  - EU-OPENSCREEN--a European infrastructure of open screening platforms for chemical
      biology.

PMID- 24742391
TI  - Work aggravated asthma; a review of the recent evidence.
AB  - BACKGROUND: The link between asthma and inhaled workplace exposures has been long
      appreciated, and yet aggravation of asthma symptoms by work conditions, known as
      work-aggravated asthma (WAA), remains relatively common. SOURCES OF DATA: A
      review of the literature published over the last 3 years was carried out, and
      additional key articles were included from outside this timeframe. AGREEMENT: WAA
      is commonly reported by workers with asthma. One published assessment of 12
      studies identified a median prevalence of 21.5% among workers with asthma.
      Commonly reported causes included a variety of inhaled dusts, smoke, vapours,
      fumes, gases and mists, common and workplace-specific aeroallergens, physical
      environmental factors including temperature and humidity and physical activity at
      work. CONTROVERSY: Remains in relation to definition, and how to distinguish WAA
      from occupational asthma in which there is sensitization to an agent in the
      workplace. Both these areas, and the development of workplace interventions to
      reduce WAA, are timely topics for future research.

PMID- 24742392
TI  - Lessons learned in community research through the Native Proverbs 31 Health
      Project.
AB  - BACKGROUND: American Indian women have high rates of cardiovascular disease
      largely because of their high prevalence of hypertension, diabetes, and obesity.
      This population has high rates of cardiovascular disease-related behaviors,
      including physical inactivity, harmful tobacco use, and a diet that promotes
      heart disease. Culturally appropriate interventions are needed to establish
      health behavior change to reduce cardiovascular disease risk. COMMUNITY CONTEXT:
      This study was conducted in Robeson County, North Carolina, the traditional
      homeland of the Lumbee Indian tribe. The study's goal was to develop, deliver,
      and evaluate a community-based, culturally appropriate cardiovascular disease
      program for American Indian women and girls. METHODS: Formative research,
      including focus groups, church assessments, and literature reviews, were
      conducted for intervention development. Weekly classes during a 4-month period in
      4 Lumbee churches (64 women and 11 girls in 2 primary intervention churches; 82
      women and 8 girls in 2 delayed intervention churches) were led by community lay
      health educators. Topics included nutrition, physical activity, and tobacco use
      cessation and were coupled with messages from the Proverbs 31 passage, which
      describes the virtuous, godly woman. Surveys collected at the beginning and end
      of the program measured programmatic effects and change in body mass index.
      OUTCOME: Churches were very receptive to the program. However, limitations
      included slow rise in attendance, scheduling conflicts for individuals and church
      calendars, and resistance to change in cultural traditions. INTERPRETATION:
      Churches are resources in developing and implementing health promotion programs
      in Christian populations. Through church partnerships, interventions can be
      tailored to suit the needs of targeted groups.

PMID- 24742393
TI  - Student-reported school drinking fountain availability by youth characteristics
      and state plumbing codes.
AB  - INTRODUCTION: Caloric intake among children could be reduced if sugar-sweetened
      beverages were replaced by plain water. School drinking water infrastructure is
      dictated in part by state plumbing codes, which generally require a minimum ratio
      of drinking fountains to students. Actual availability of drinking fountains in
      schools and how availability differs according to plumbing codes is unknown.
      METHODS: We abstracted state plumbing code data and used the 2010 YouthStyles
      survey data from 1,196 youth aged 9 through 18 years from 47 states. We assessed
      youth-reported school drinking fountain or dispenser availability and differences
      in availability according to state plumbing codes, sociodemographic
      characteristics, and area-level characteristics. RESULTS: Overall, 57.3% of youth
      reported that drinking fountains or dispensers in their schools were widely
      available, 40.1% reported there were only a few, and 2.6% reported that there
      were no working fountains. Reported fountain availability differed significantly
      (P < .01) by race/ethnicity, census region, the fountain to student ratio
      specified in plumbing codes, and whether plumbing codes allowed substitution of
      nonplumbed water sources for plumbed fountains. "Widely available" fountain
      access ranged from 45.7% in the West to 65.4% in the Midwest and was less common
      where state plumbing codes required 1 fountain per more than 100 students (45.4%)
      compared with 1 fountain per 100 students (60.1%) or 1 fountain per fewer than
      100 students (57.6%). CONCLUSION: Interventions designed to increase consumption
      of water may want to consider the role of plumbing codes in availability of
      school drinking fountains.

PMID- 24742394
TI  - Prevalence of cigarette advertising and other promotional strategies at the point
      of sale in St Louis, Missouri: analysis by store type and distance from a school.
AB  - INTRODUCTION: Point-of-sale advertising provides an opportunity for the tobacco
      industry to communicate with current and potential smokers. The US Family Smoking
      Prevention and Tobacco Control Act allows states to implement policies requiring
      that tobacco products be placed out of sight, and the Food and Drug
      Administration is considering banning point-of-sale advertising within 1,000 feet
      of schools. Our objective was to compare cigarette point-of-sale advertising near
      schools with grades prekindergarten through 12 and by store type. METHODS: All
      registered cigarette retailers (n = 1,229) and schools (n = 581) in the city of
      St Louis and St Louis County were geocoded and mapped by using ArcGIS. Retailers
      were divided into 2 groups, those within 1,000 feet and those within 1,001 to
      2,000 feet of a school; 200 retailers from each group were randomly selected. We
      assessed tobacco interior and exterior advertising, brands advertised, discounts,
      gifts with purchase, "no sales to minors" signage, and cigarette functional items
      (eg, advertising on shopping baskets). Analyses were done by distance from a
      school and store type. RESULTS: We analyzed 340 retailers. Most retailers within
      1,000 feet (91.2%) and from 1,001 to 2,000 feet (94.2%) of a school displayed
      cigarette advertising (P = .20). Convenience stores had the highest number of
      interior ads. In multivariable models, distance from school explained 0.2% of the
      variance in total advertising. CONCLUSION: Cigarette point-of-sale advertising is
      highly prevalent in St Louis within 1,000 feet of schools. A ban based on
      distance from a school might decrease advertising exposure, but its effect on
      smoking prevalence is yet to be determined because advertising farther from
      schools would still prevail.

PMID- 24742395
TI  - Multiple chronic conditions among US adults: a 2012 update.
AB  - The objective of this research was to update earlier estimates of prevalence
      rates of single chronic conditions and multiple (>2) chronic conditions (MCC)
      among the noninstitutionalized, civilian US adult population. Data from the 2012
      National Health Interview Survey (NHIS) were used to generate estimates of MCC
      for US adults and by select demographic characteristics. Approximately half (117
      million) of US adults have at least one of the 10 chronic conditions examined
      (ie, hypertension, coronary heart disease, stroke, diabetes, cancer, arthritis,
      hepatitis, weak or failing kidneys, current asthma, or chronic obstructive
      pulmonary disease [COPD]). Furthermore, 1 in 4 adults has MCC. 

PMID- 24742396
TI  - Parks and health: aligning incentives to create innovations in chronic disease
      prevention.

PMID- 24742398
TI  - Glucarpidase Intervention for Delayed Methotrexate Clearance.
AB  - OBJECTIVE: To review and evaluate the current published literature on the
      effectiveness and safety of glucarpidase and to determine its potential role in
      clinical practice. DATA SOURCES: A PubMed literature search from 1946 to January
      2014 was performed using the search terms carboxypeptidase G2, glucarpidase, high
      dose methotrexate, and leucovorin rescue. Additional references were identified
      by reviewing the references from the PubMed search articles. STUDY SELECTION AND
      DATA EXTRACTION: English-language clinical trials and retrospective studies
      assessing the safety and effectiveness of glucarpidase were included. Case
      reports were excluded. DATA SYNTHESIS: A total of 5 non-randomized, prospective
      studies and 1 retrospective study evaluated the effectiveness and safety of
      glucarpidase in patients receiving high-dose methotrexate. In these studies,
      glucarpidase conferred a >87% reduction in serum methotrexate concentrations
      (sMTX) and was well tolerated. Although a substantial reduction in sMTX was
      observed, clinically significant outcomes such as the need for dialysis, time to
      administration of next chemotherapy cycle, and methotrexate toxicity-related
      mortality were not consistently evaluated. CONCLUSIONS: Glucarpidase is effective
      in lowering sMTX in patients with delayed methotrexate clearance and renal
      dysfunction. Considering the relatively high cost of glucarpidase, it should be
      reserved for specific patients who have not responded to standard supportive care
      measures.

PMID- 24742399
TI  - "His" and "her" marriage? The role of positive and negative marital
      characteristics in global marital satisfaction among older adults.
AB  - OBJECTIVES: We explore gender differences in older adults' appraisals of positive
      and negative aspects of their marriages, examine how these appraisals relate to
      global marital satisfaction, and identify distinctive marital profiles associated
      with global satisfaction in men and women. METHOD: Data are from the Changing
      Lives of Older Couples Study (n = 1,110). We used a variant of principal
      components analysis to generate marital quality profiles, based on one's
      endorsement of positive and negative marital characteristics. OLS regression was
      used to detect associations between marital profiles and global marital
      satisfaction. RESULTS: Men offered more positive marital assessments than women,
      particularly on items reflecting positive treatment by one's wife. Three marital
      quality profiles emerged: Positive, Positive-Negative, and Negative. Although
      marital satisfaction was best explained by positive appraisals in both genders,
      they were less important for men than for women. The negative profile showed a
      tendency for a stronger prediction in men. DISCUSSION: Prior studies show small
      differences in men's and women's global marital satisfaction. Our work provides
      evidence that the presence and magnitude of such gender differences may vary
      based on the specific marital component considered. We discuss ways that gender
      shapes marital interactions, expectations, and perceptions, and the implications
      of our results for the well-being of married older adults.

PMID- 24742400
TI  - Domestic helpers as moderators of spousal caregiver distress.
AB  - OBJECTIVES: Although domestic helpers increasingly play a role in elder care in
      many societies, there is a lack of research on their influence on caregiver
      distress. This study aimed to examine the influence of domestic helpers on the
      relationship between stressors (the care needs of frail elders and spousal
      provision of care) and spousal caregivers' psychological distress. METHOD: This
      study was a secondary analysis of cross-sectional data collected between 2007 and
      2009 from 6,442 Hong Kong adults aged 60 or older who were applying for
      government-subsidized long-term care services and whose spouses were their
      primary caregivers. Among the spousal caregivers, 73.04% were women, 44.16% felt
      distressed, and 5.73% were assisted by domestic helpers. RESULTS: According to
      logistic regression analysis, spousal caregivers who provided personal care
      related to activities of daily living were more likely to be distressed if they
      were not assisted by domestic helpers. DISCUSSION: The findings suggest that
      domestic help may moderate the effect of stressors on spousal caregivers.
      Domestic helpers provide support not just to frail older adults but also to
      spousal caregivers. Further studies are recommended to explore the precise effect
      of domestic help on family caregivers, care receivers, and the caregiving
      process.

PMID- 24742403
TI  - Trauma registry -- a necessity of modern clinical practice.
AB  - INTRODUCTION: Traumas represent the cause of 10 % of deaths in the entire world.
      The successful development of trauma systems, including the use of trauma
      registries, played a significant part in lowering the mortality and the
      disabilities due to injuries resulted from trauma. METHOD: Review of the
      literature using computerized database of National Library of Medicine and the
      International Institutes of Health MEDLINE using PubMed interface. There were
      selected the articles that address the issue of trauma registry from the
      different world trauma systems. RESULTS: Trauma registries have developed once
      they were introduced in centers and trauma systems in the United States of
      America in 1970. First trauma database processed on computers was created in 1969
      in Cook County Hospital in Chicago. This database became the prototype of trauma
      registry in Illinois which started gathering information from 50 designated
      hospitals across the entire state in 1971.Countries with limited resources were
      able to start useful trauma registers. Continuous financing and dedicated
      personnel inside the team are two essential factors in the success of a trauma
      registry. NISS (New Injury Severity Score) higher than 15 is a widely used
      inclusion criteria in the trauma register. Exclusion is represented by patients
      admitted at over 24 hours after the accident, those declared dead before hospital
      arrival or with no signs of life on arrival in hospital. In addition, it is
      recommended that asphyxia,drowning and burns to be excluded. CONCLUSION: The
      improvements regarding the treatment of multi-traumatized people in developing
      countries depend on establishing and performance of trauma systems, where trauma
      registry represents a part of these systems infrastructure.

PMID- 24742402
TI  - Capturing the biological impact of CDKN2A and MC1R genes as an early predisposing
      event in melanoma and non melanoma skin cancer.
AB  - Germline mutations in CDKN2A and/or red hair color variants in MC1R genes are
      associated with an increased susceptibility to develop cutaneous melanoma or non
      melanoma skin cancer. We studied the impact of the CDKN2A germinal mutation
      p.G101W and MC1R variants on gene expression and transcription profiles
      associated with skin cancer. To this end we set-up primary skin cell co-cultures
      from siblings of melanoma prone-families that were later analyzed using the
      expression array approach. As a result, we found that 1535 transcripts were
      deregulated in CDKN2A mutated cells, with over-expression of immunity-related
      genes (HLA-DPB1, CLEC2B, IFI44, IFI44L, IFI27, IFIT1, IFIT2, SP110 and IFNK) and
      down-regulation of genes playing a role in the Notch signaling pathway. 3570
      transcripts were deregulated in MC1R variant carriers. In particular, genes
      related to oxidative stress and DNA damage pathways were up-regulated as well as
      genes associated with neurodegenerative diseases such as Parkinson's, Alzheimer
      and Huntington. Finally, we observed that the expression signatures indentified
      in phenotypically normal cells carrying CDKN2A mutations or MC1R variants are
      maintained in skin cancer tumors (melanoma and squamous cell carcinoma). These
      results indicate that transcriptome deregulation represents an early event
      critical for skin cancer development. 

PMID- 24742404
TI  - Colorectal cancer with liver metastases -- is there a chance for cure?
AB  - Combined treatment with chemotherapy and surgery is the currently accepted
      standard for patients with metastatic colorectal cancer which can be rendered to
      resectability and a very efficient way to increase survival of patients with
      hepatic metastases from colorectal cancer. Cooperation between surgeons and
      oncologists is mandatory to insure these patients' best chance for survival.
      Patients with resectable disease must follow adjuvant chemotherapy, while
      patients with initially unresectable marginally resectable disease after
      downsizing with the help of chemotherapy must be given the chance of surgical
      reevaluation for having the metastatic disease resected,and then follow adjuvant
      chemotherapy. An impressive amount of new surgical techniques warrants the
      success of hepatic resection in metastatic disease while a whole constellation of
      novel chemotherapeutical and even more effective targeted agents assure better
      response rates, surgical resection rates and overall survival in these patients.

PMID- 24742405
TI  - The place of radiofrequency ablation in the multimodal treatment of cervical
      cancer. Our experience.
AB  - INTRODUCTION: Genital cancers benefit from standardized treatment plans which
      include: surgery and radio chemotherapy.Lately, treatments involving thermal
      ablations have entered the clinical use, as they destroy the tumors by the use of
      different energy sources. Our study aims at establishing a precise role of RFA in
      current treatment protocols of cancer of the uterine cervix. MATERIAL AND METHOD:
      We performed a 5-year (2008-2013)prospective study in which we analyzed the use
      of RFA inpatients treated for cancer of the uterine cervix at our clinic.RFA was
      used, on selective criteria, in bleeding tumors of the uterine cervix in patients
      with acute secondary anaemia(Hb=7-11g dl). The results revealed the haemostatic
      role of the method, RFA being the only non surgical method through which one can
      achieve quick haemostasis (20 min.). 61 patients were clinically observed, with
      ages between 39 and 73, and the number of procedures performed was 61.
      CONCLUSION: RFA is useful in the treatment of cancers of the uterine cervix, in
      all stages of the disease, and it achieves quick haemostasis. RFA can be
      considered an additional treatment option in neoadjuvant tumor palliation. The
      method can be associated with surgery and radio chemotherapy. Its assets are low
      specific morbidity (1,6%) and mortality (0%). We consider that RFA is on its way
      to an important place in oncology treatment protocols.

PMID- 24742406
TI  - Retrospective study minimally invasive management of postoperative lithiasis of
      the common bile duct.
AB  - INTRODUCTION: Postoperative common bile duct (CBD) lithiasis holds a significant
      place in the bilio-pancreatic pathology, both due to its high frequency as well
      as to the diagnostic and treatment issues it triggers. MATERIAL AND METHODS:
      Based on a 5-year experience (2008-2012), assessed retrospectively, totalling 51
      patients with postoperative lithiasis of CBD, we tried to elaborate on several
      recommendations for the treatment of this pathology. The recommendations were
      guided by the existing alternative therapeutic options and by the ideas in the
      literature regarding the results achieved by every manner of treatment. RESULTS:
      The rate of clearance of the CBD was of 93.6%,the morbidity rate was of 10.65%
      and the mortality rate was of 0%, which entitles us to deem the effectiveness of
      the minimally invasive treatment as maximum in the treatment of this pathology.
      CONCLUSIONS: The endoscopic treatment of postoperative lithiasis of the CBD
      proved to be possible, efficient and we believe it good to be used as a
      principle; open surgery should be the solution in case of failures or of
      contraindications to minimally invasive treatment.

PMID- 24742407
TI  - Parastomal hernias -- clinical study of therapeutic strategies.
AB  - Parastomal hernias are parietal defects adjacent to the stomasite, after
      ileostomy and colostomy. Their incidence is variable and they are generally
      underestimated. METHODS: Between 2001 and 2010 at the First Surgical Clinic Iasi,
      we treated 861 incisional hernias, of which there were 31 parastomal hernias in
      26 patients (3%), 5 of which were recurrent parastomal hernias. Parastomal
      hernias have been explored clinically, through imaging and
      intraoperatively.Because our experience and literature review have demonstrated
      that a mesh repair is a safe procedure in the treatment of parastomal hernia, in
      2010 we initiated a prospective randomized trial on the use of prophylactic
      polypropylene mesh at the time of stoma formation to reduce the risk of
      parastomal hernia. We enrolled in the study 20 patients with mesh implanted at
      the primary operation and 22 patients without mesh. The inclusion criteria were:
      patients with low rectal cancer, stage II-III, irradiated, obese, with a history
      of hernias, patients who do physical work. RESULTS: Most parastomal hernias were
      asymptomatic; only six cases with parastomal hernias required emergency surgical
      treatment. We performed local tissue repair in 16 cases (4 cases with recurrent
      parastomal hernia, stoma relocation in one case), sublay mesh repair in 15 cases
      (one case with recurrent parastomal hernia; stoma relocation in 5 cases).
      Postoperative morbidity registered included 4 wound infections (one case after
      mesh repair which required surgical reintervention) and stoma necrosis in one
      case with strangulation parastomal hernia with severe postoperative evolution and
      death. After local tissue repair recurrences were seen in 6 cases, after mesh
      repair we registered recurrence only in one case and no relapse after the
      relocation of the stoma. The patients with prophylactic mesh at the time of stoma
      formation to reduce the risk of parastomal hernia were followed for a median of
      20 months(range 12 to 28 months) by clinical examination and ultrasound exam
      every 3 months. We registered 6 recurrences(27,2%), all in the no mesh cohort. We
      have not seen any morbidity in patients from the mesh group. CONCLUSIONS:
      Parastomal hernia is a relatively rare disease compared to the number of
      incisional hernias. With increasing life expectancy stands we noted increased
      incidence of parastomal hernia as well. Prophylactic use of mesh during the
      primary operation is a safe procedure and reduces the risk of parastomal hernia.

PMID- 24742408
TI  - Preoperative radiotherapy in rectal cancer treatment -- is it really a gold
      standard?
AB  - Preoperative radiotherapy in the treatment of rectal cancer was thought to be an
      achievement of similar importance to total mesorectal excision (TME), for the
      therapeutic management of rectal malignancies. However, numerous criticisms have
      been discussed in this field lately. We have analysed the two main purposes of
      preoperative radiation: possible sphincter preservation and the conversion of a
      non-resectable tumor into a resectable one in a series of 31 consecutive
      patients, operated in our clinic. In 20 of them, preoperative radio
      chemoradiotherapy was applied, while 11 patients were firstly operated and then
      irradiated. The surgical procedure included total mesorectal excision in 30
      patients, as part of a low anterior resection,in 13 cases and of an abdominal
      perineal resection, in the other 17 cases. We have found that preoperative
      radiotherapy improves the local recurrence rate but has no influence on the
      overall survival rate. However, we should not overlook the adverse effects of
      this method: toxicity of radiotherapy on the small bowel and the urinary bladder,
      the healing of the perineal wounds and the risk of anastomotic leaks. We
      concluded in favor of elective preoperative radiotherapy in selected cases: any
      T4 tumors, T3 tumors which threaten the mesorectal fascia on MRI, whenever there
      is a suspicion of nodal involvement and also for very low tumors.

PMID- 24742409
TI  - Occult thyroid carcinoma in our experience -- should we reconsider total
      thyroidectomy for benign thyroid pathology?
AB  - BACKGROUND: The reported incidence rate of occult thyroid carcinoma in patients
      operated for benign thyroid pathology has been much higher than expected in the
      last years,especially for multinodular goitre, which raises the question about
      which should the proper surgical management for these cases be. AIM: To assess
      the incidence rate of OTC in a single medium volume surgical center and to
      establish the correct indication for initial surgical management, as well as to
      identify the benign thyroid pathology most frequently associated with OTC. We
      also reviewed the relevant scientific literature on this topic. MATERIAL AND
      METHOD: We conducted a retrospective study in the General Surgery Clinic of
      "Prof. dr. Agrippa Ionescu" Clinical Emergency Hospital, Bucharest, on a series
      of 145 patients who underwent surgical interventions for preoperatively diagnosed
      benign thyroid pathology over a ten year period, between 1st January 2002 - 31st
      December 2012. All cases of known thyroid cancer were excluded. RESULTS:
      Incidence rate of occult thyroid carcinoma in our series was 6.9 % (10 out of 145
      patients), 80 % of them being diagnosed with multinodular goitre and two cases
      (20 %) with Hashimoto's lymphocytic thyroiditis. 6.8 % of all patients with
      multinodular goitre were found to present occult carcinoma,but this association
      was without statistical significance(p 0.05). Incidence rate of occult cancer
      among patients with Hashimoto thyroiditis was proved to be as high as
      28.6%,statistically significant (p=0.020). The mean size of postoperatively
      diagnosed occult microcarcinoma was 7 mm, ranging between 3 mm and 14 mm, 90% of
      them being smaller than 1cm. Histologically, papillary microcarcinoma was found
      in all cases. The mean age of the patients diagnosed with occult microcarcinoma
      was 47.8 years with majority of the female gender. The most frequent operation
      performed was total thyroidectomy (70.8%). Overall morbidity in our series was
      6.9% with a 0.7 % mortality rate (1 case). CONCLUSIONS: In our opinion, primary
      total thyroidectomy should be performed as the procedure of choice for the most
      part of preoperatively diagnosed benign thyroid pathology and particularly for
      multinodular goitre and Hashimoto thyroiditis,in order to radically resect all
      possible foci of aggressive thyroid microcarcinomas.Abbreviations and Acronyms:
      OTC (Occult Thyroid Carcinoma), PTMC (Papillary Thyroid Microcarcinoma); TT(Total
      Thyroidectomy), MNG (Multinodular Goitre), GD(Graves' disease), TNG (Toxic
      Nodular Goitre), FNAB(fine-needle aspiration biopsy).

PMID- 24742410
TI  - Laparoscopic sleeve gastrectomy improves reproductive hormone levels in morbidly
      obese males -- a series of 28 cases.
AB  - BACKGROUND: Obese males frequently present with low androgen levels that may
      improve after weight loss achieved by bariatric surgery. Laparoscopic sleeve
      gastrectomy (LSG) has been used often in the last decade as treatment for morbid
      obesity. The aim of this study was to evaluate modifications in the male
      reproductive hormone profile after LSG. PATIENTS AND METHODS: The prospective
      study included 28 males with body mass index (BMI) 35 kg m2 who underwent
      LSG.Total Testosterone (TT), Sex Hormone Binding Globulin(SHBG) and Luteinizing
      hormone (LH), together with biochemical and anthropometric data, were evaluated
      at baseline and after LSG. RESULTS: Baseline patients had a mean BMI of 50.10 (+
      11.19)kg m2, SHBG 23.37 (+-17.47) nmol L, LH 3.83 (+-1.76)mUI ml and TT 8.31 (+
      3.24) nmol L. After LSG, patients showed a mean BMI of 35.87 (+-7.02) kg m2 (p
      0.001),SHBG 37.81 (+-18.95) nmol L (p 0.05), LH 4.76 (+-2.49)mUI ml (p 0.05),
      whereas mean TT was 12.7 (A+-3.8) nmol L(p 0.001). The percentage of excess body
      weight loss (%EBL)was 43.07 (+-9.56) and metabolic syndrome prevalence decreased
      significantly from 75% to 25% (p 0.001). CONCLUSIONS: Beyond BMI loss, LSG
      significantly improved reproductive hormone levels in morbidly obese males.

PMID- 24742411
TI  - Management of hepatocellular carcinoma -- experience of a single center.
AB  - BACKGROUND AND AIMS: Hepatocellular carcinoma (HCC) is the fifth most common
      cancer worldwide and the third most common cause of cancer-related death. We aim
      to study the diagnosis and treatment options for HCC. METHODS: We used standard
      methods of diagnosis for HCC:radiology, determining serum alpha fetoprotein
      (AFP). We included 190 patients diagnosed with HCC between April 2011 and May
      2012. RESULTS: All patients were classified and treated according to the BCLC
      staging. Our study included 43 patients with early stage HCC, 58 patients with
      intermediate stage HCC (Stage B) and 89 patients with advanced stage HCC (Stage
      C). Most patients in the early stage underwent local ablation, while TACE was
      preferred in 46 patients in the intermediate stage.Systemic therapy was the most
      frequent treatment for patients in the advanced stage (48 patients), followed by
      Sorafenib (16 patients). 21 patients with end-stage disease did not receive
      treatment. Survival rates depended on the HCC stage: 2 - 18 months in the
      intermediate stage and 1 - 12 months in the advanced stage. CONCLUSION: Early
      diagnosis of HCC is essential in improving the patients outcomes, as there are
      several classic therapeutic options and new emerging ones addressing patients
      with early stage disease.

PMID- 24742412
TI  - The use of mechanical suture in the treatment of Hirschsprung's disease:
      experience of 17 cases.
AB  - INTRODUCTION: Hirschsprung's disease, or congenital megacolon,is a malformation
      characterised by the absence of ganglion cells in the distal bowel. Most often,
      the aganglionic segment includes the rectosigmoid, but it may extend proximally
      to variable length. In late years, significant improvements regarding the
      surgical treatment of Hirschsprung's disease were made, by the introduction of
      both one-stage transanalendorectal pull-through a laparoscopically assisted or
      not - and mechanical suture devices. AIM: The purpose of this paper is to analyse
      our results with modified Duhamel procedure by using mechanical sutures for
      construction of a side-to-side colo-rectal anastomosis. MATERIALS AND METHOD: We
      analysed 17 congenital megacolon cases operated in our department between 2007 -
      2011 by the same pediatric surgical team, using the modified Duhamel technique
      performed with mechanical suture. It is the first series operated in our country
      using this procedure. 2 patients had a long colonic aganglionosis, 2 patients had
      a short aganglionotic segment and 13 patients had the common form of the disease.
      Mainly, we focused on technical details,hospitalization period, and immediate and
      late complications. RESULTS: The mean hospitalization period was of 9
      days.Mortality in our series was 0. Postoperative complications consisted in
      minor bleeding (5 cases), adhesions and mechanical occlusion (1 case), and
      subocclusive symptoms due to remnant septum with subsequent fecaloma formation in
      the rectal ampula (4 cases). All of our operated cases had consequently a very
      good fecal continence. CONCLUSIONS: We think that usage of mechanical suture
      devices in a single stage Duhamel procedure is extremely beneficial regarding
      both complication rate and hospitalisation time.This technique is safe, simple
      and efficient.

PMID- 24742413
TI  - Motor criteria evaluation of iso-anisoperistaltic graft in oesophageal
      reconstruction -- an experimental study of isolated colic graft motility pattern
      in dogs.
AB  - In the medical literature there are more than one opinion in favour of the
      isoperistaltic interposed loop, considering it to render a higher propulsive
      activity and thus with much better functionality, with less intense symptoms of
      regurgitation,reflux or aspiration. Technically, however, due to anatomical
      relationships, anisoperistaltic graft interposition is more convenient. Is this
      detrimental to functionality? What is the best peristaltic model? At first sight,
      it seems that due to the local anatomy and surgical technique involved, we
      compromise at the expense of better functionality. To find the answer to these
      questions, starting from the typical pattern of colonic motility in the
      transverse and left colon, we need to identify new motor behaviour of the
      isolated colic segment. Because motor activity is generated by electric waves
      discharged from the area control centre, their electromyographic registration
      would allow finding the contractile pattern of a transplanted loop.

PMID- 24742414
TI  - Acute abdominal complications following hip surgery.
AB  - Hip surgeries are some of the most common and successful orthopedic procedures.
      Although rarely, abdominal complications do occur and are associated with
      unfavorable outcomes.We aimed to identify and describe the severe abdominal
      complications that appear in patients under-going elective or traumatic hip
      surgery. A four year retrospective electronic database research identified 408
      elective primary hip replacements,51 hip revisions and 1040 intra and
      extracapsular proximal femur fractures. Out of these, three males and 4 females
      between 64 - 84 years old were identified to have developed acute abdominal
      complications: perforated acute ulcer (3),acute cholecystitis (2), volvulus (1),
      toxic megacolon with peritonitis (1) and acute colonic pseudo-obstruction
      (1).Complications debuted 3 - 10 days after index orthopedic surgery. Acute
      perioperative abdominal complications are rarely encountered during orthopedic
      surgery. When these do occur, they do so almost exclusively in patients with
      hippathology, comorbidities and most often lead to life threatening situations.
      We thus emphasize the need for early identification and appropriate management by
      both orthopedic and general surgery doctors in order to improve patient safety.

PMID- 24742415
TI  - Risk factors influencing the surgical outcome in 138 consecutive patients with
      infrarenal aortic aneurysm: experience at the Cluj-Napoca Cardiovascular Surgery
      Center.
AB  - Abdominal aortic aneurysms represent a common pathologic condition, with an
      increasing incidence in the last decades. Unfortunately, the mortality rate in
      ruptured abdominal aortic aneurysms has also increased. The aim of this
      retrospective study was to determine the risk factors that could interfere with
      the surgical outcome of these patients, especially with the perioperative
      morbidity and mortality rates. MATERIALS AND METHODS: In this study we included
      138 consecutive patients with infrarenal aortic aneurysm, who underwent elective
      repair (for chronic aortic aneurysm) or emergency repair (for ruptured aortic
      aneurysm), in the Cluj-Napoca Cardiovascular Surgery Clinic between January 2003
      and December 2011. We noted the most frequently associated diseases and
      perioperative complications among the studied population. Three types of
      interventions were performed:tubular graft interposition, aortobiiliac bypass and
      aortobifemoral bypass. RESULTS: The perioperative mortality in the elective
      repair group was 5.68% (5 - 88), while in the emergency repair group it was 46%
      (23 - 50). CONCLUSIONS: Ruptured abdominal aortic aneurysm continues to represent
      a condition associated with substantial risks and high mortality. Selective
      screening and elective repair are therefore necessary for the improvement of the
      survival rate for patients with infrarenal aortic aneurysm.

PMID- 24742416
TI  - Transarticular approach and retrograde plate osteosynthesis (TARPO) using
      implants with angular stability -- a series of 17 cases of complex distal femoral
      fractures type C3/AO.
AB  - AIM: The aim of this retrospective study was to evaluate the outcome of distal
      femoral fractures type C3 AO, using TARPO technique and plates with angular
      stability. MATERIAL AND METHODS: The study included 17 fractures type C3 AO, with
      4 open fractures: 1 type I, 1 type II, and 2 type IIIA with bone loss Gustilo.
      All patients were operated by TARPO technique using Less Invasive Stabilization
      System-LISS (4 cases), Locked Compression Plates-LCP (8 cases) and plates with
      polyaxial stability (5 cases). The excellent stability of the construct allowed
      fast knee rehabilitation. The follow-up period included at least 12 months.
      RESULTS: 15 fractures healed within a mean time of 12.6 weeks,while 2 cases with
      open fractures and bone loss required secondary bone grafting. We recorded no
      infection or implant failures. The outcome using Neer scale was excellent in 9
      cases and satisfactory in 7 cases (1 patient with discontinued follow-up).
      CONCLUSIONS: This demanding TARPO technique has the advantage of a faster rate of
      union and improved exposure of the knee joint. The locked plates provide a unique
      alternative in distal femoral fractures type C3 AO, as well as in osteoporotic
      and open fractures.

PMID- 24742417
TI  - Ureteroscopy -- first-line treatment alternative in ureteral calculi during
      pregnancy?
AB  - BACKGROUND: Urolithiasis during pregnancy is not common but remains both a
      diagnostic and treatment challenge. The aim of the study was to assess the
      ureteroscopy results as definitive treatment option in pregnant women with
      obstructive ureteral calculi. MATERIAL METHODS: Between 2006 and 2012, in our
      clinical department, 54 pregnant women underwent active treatment for ureteral
      lithiasis and in 38 of these cases ureteroscopy was applied as definitive
      therapy. The average patients age was 27.2 years (range 20-37 years) and the
      gestation period varied between 9 to 35 weeks. Flank pain was the common
      presenting symptom (52 54 cases), 4 women had associated fever, and 14 complained
      of irritative voiding symptoms.Semirigid ureteroscopy was the first choice
      alternative for the first 2 trimesters while flexible approach or double J in
      dwelling were preferred for patients in the last trimester of pregnancy. RESULTS:
      Semirigid ureteroscopy allowed stone treatment in 28 32 cases. In 17 patients,
      calculi fragmentation using Ho:YAG laser or ballistic lithotripsy were performed,
      while in 11 cases, the stone was removed intact. Minor intraoperative
      complications were encountered in 5 patients. Postoperatively,urinary tract
      infection developed in 4 patients, renal colic in 2 and prolonged hematuria in
      one case, while 4 patients complained of stent-induced bladder irritation.
      Flexible ureteroscopy was successfully completed in all patients. There were no
      complications related to this procedure. All pregnancies were carried out to full
      term. CONCLUSIONS: Ureteroscopy may be considered a safe and effective first-line
      definitive therapeutic option in pregnant patients requiring intervention for
      ureteral stone.

PMID- 24742418
TI  - Temporary protective loop ileostomy in open low rectal resection -- an
      alternative technique.
AB  - The paper presents a simplified method for performing a temporary protective loop
      ileostomy as a result of our experience in 33 cases of low rectal resections for
      cancer.The particularities of this technique are: the skin incision is smaller
      than the muscle one, the seromuscular layer of the loop is fixed at the skin
      level only by marking a small portion of the antimesenteric wall, with no mucosal
      eversion. No supporting rod is used. The reversal requires resection of the
      thickened freemargins and enterorrhaphy. It involves a direct approach and avoids
      median laparotomy and segmental bowel resection.There was no case of peristomal
      abscess, bleeding, prolapse,retraction of the loop after the stoma was formed.
      Four patients(12.12%) had peristomal dermatitis. Five patients (15.62%) had high
      output fluid losses with electrolyte disorders, one of them(3.12%) with acute
      renal failure. Closure was performed after 6 weeks on average for the colorectal
      anastomoses and 10 weeks for the coloanal ones. We recorded a case (3.12%) of
      enterocutaneous fistula that was managed conservatively and 4 cases(12.12%) of
      incisional hernia, all of them surgically treated. No mortality was attributed to
      either creation or closure of the temporary loop ileostomy. It is a simple and
      fast technique in accordance with the temporary character of its indication.

PMID- 24742419
TI  - Multiple visceral resection after locoregional recurrence of signet ring cell
      gastric cancer -- case report and literature review.
AB  - Recurrence is the most important cause of treatment failure in patients with
      advanced gastric cancer, even after curative surgery. Surgery plays an important
      role in these patients,even in cases of multivisceral involvement. In selected
      cases good biological resources - surgery is the only viable choice to prolong
      survival. This report describes the case of a 41 year-old patient presenting a
      locoregional recurrence with multiple visceral involvement at 15 months after
      radical subtotal gastrectomy with D2 lymph node dissection for antral gastric
      cancer.

PMID- 24742420
TI  - Pyoderma gangrenosum, rare parietal complication after colorectal surgery.
AB  - Pyoderma gangrenosum (PG) is a rare chronic destructive inflammatory skin disease
      characterized by the presence of nodules and pustules with progressively
      enlarging ulcers and orcutaneous necrosis. In most cases PG is idiopathic, but
      sometimes it is associated with conditions that often have vasculitis, such as
      gammapathies, inflammatory bowel diseases or chronic arthritis. PG is neither
      infectious nor gangrenous,but some authors advanced the theory that an infectious
      etiology (streptococci and staphylococci) could be incriminated.Recently, there
      are reports in the literature stating that PG is a condition that can occur after
      local trauma, especially surgery.We report the case of a 73 year old man who
      presented himself to the Surgery Department with rectal adenocarcinoma and
      postoperatively developed well-demarcated, vegetative plaques,ranging from 2 to 5
      cm in diameter, with central ulceration associated with necrosis and a purulent
      secretion, delimitated by raised, dusky erythematous borders. These lesions were
      located on the abdomen and it is important to mention that the injuries occurred
      at the site of surgical stitches used during the rectum amputation surgery, with
      no other anatomical locations,pruritus or pain associated. We performed two
      different histopathological examinations for this patient, regarding the rectal
      specimens and the cutaneous specimen. The first examinations revealed rectal
      adenocarcinoma and nonspecific colitis. The second examination was concluded with
      the diagnosis of pyoderma gangrenosum, the ulcerative stage. The patient had a
      very good clinical response to systemic steroid therapy.

PMID- 24742421
TI  - Giant thoraco-abdominal tumor -- a surgical challenge. Case report.
AB  - BACKGROUND: During the last three decades, several improvements in surgical and
      anesthetic techniques have allowed a better management of primary and secondary
      tumors of the chest wall. OBJECTIVES: Chest wall tumors, regardless of their
      location,anterior, posterior or lateral, have always been a challenge for the
      thoracic surgeon through technical and tactical problems they entail. The most
      common techniques to reconstruct a full thickness defect are by the use of
      alloplastic material and filling the soft tissue defect with myocutaneous flap.
      METHOD: We present the unusual case of a 45 years old patient with a giant right
      thoraco-abdominal tumor, developing for the last 22 years. The tumor occupied the
      lower half of the right hemithorax and the right hemi abdomen, down to the right
      iliac crest. The tumor also developed inside the thoracic cavity, with the
      invasion of the last 3 ribs, of the diaphragm(partial) and with intra-abdominal
      invasion of a liver section and the right kidney. RESULTS: The surgery team had
      special problems related to:providing training and logistics, in-block tumor
      resection in oncological limits, followed by complex thoraco-abdominal
      reconstruction. The results were very good, with a favorable postoperative
      evolution, without any complications, the patient being discharged with the
      recommendation to come for follow-up on his condition. CONCLUSIONS: A complex
      surgical intervention proved to be the only solution for saving the patient, for
      which the life due to the tumor's size became almost unbearable.

PMID- 24742422
TI  - Complex malformation of the inferior vena cava.
AB  - Malformations of the inferior vena cava (IVC) are rare presentations, exceptional
      in children, and are usually asymptomatic.They are caused by disturbances in the
      embryological formation of the venous system or can develop as a result of
      perinatal venous thrombosis with secondary impairment of the venous development.
      We report the case of a 14 year old boy,admitted for pediatric evaluation before
      undergoing plastic surgery in order to remove superficial varicose veins of the
      lower abdomen. The patient presents with inequality in circumference and length
      of the legs. Laboratory investigations are normal and the abdominal ultrasound
      describes hypoplasia of the retrohepatic segment of the inferior vena cava. The
      diagnosis of complex malformation of the abdominal deep venous system
      (retrohepatic vena cava atresia, cavo-caval anastomosis through azygos veins,
      abnormal formation of the inferior vena cava with the absence of the left iliac
      vein) was established through a CT angiography. The presence of abdominal
      varicose dilations should indicate the necessity to closely look for
      malformations of the portal and/or caval venous systems.

PMID- 24742423
TI  - Prehepatocholedochal proper hepatic artery. Rare anatomical variant. Surgical
      considerations. Case report.
AB  - In classical anatomic variants, the proper hepatic artery (PHA)continues the
      common hepatic artery (CHA) after the gastroduodenal artery (GDA) detaches itself
      and divides into the right hepatic artery (RHA) and left hepatic artery (LHA),
      the proper hepatic artery being located to the left of the hepatocholedochal duct
      (HCD). This paper presents an abnormal positioning of the PHA placed before the
      HCD with an increased diameter of about 5-7 mm, which could be confused with the
      HCD. We present the case of a 57 year-old woman diagnosed with acute lithiasic
      cholecystitis, associated with hypersplenism and hypertension. The literature
      mentions manifold anatomical variants of arterial liver vascularization,including
      PHA. For this reason, this paper presents an overview of similar cases that can
      be found in medical literature. The aforementioned case is a rare topographic
      anatomy for the PHA that can easily pass for HCD especially during celioscopy,
      therefore it is crucial for this to be acknowledged by all surgeons.

PMID- 24742424
TI  - Umbilical endometriosis associated with large umbilical hernia. Case report.
AB  - Umbilical endometriosis is a rare condition, usually following laparoscopic and
      surgical procedures involving the umbilicus.Spontaneous umbilical endometriosis
      occurring without any previous abdominal or uterine surgery is extremely rare.
      The maximal depth of penetration of the umbilical endometriosis described is up
      to fascial level. There have been only two cases of endometriosis reported
      arising within umbilical hernia. The authors report a case of a patient with
      spontaneous umbilical endometriosis associated with a large umbilical hernia,
      treated by surgical excision and mesh repair of the abdominal wall. To the best
      of our knowledge, this is the first described case of the association of
      umbilical endometriosis with a large umbilical hernia that requires prosthetic
      mesh repair of the abdominal wall defect.

PMID- 24742425
TI  - Bilateral pneumothorax and pneumomediastinum after orthognathic surgery.
AB  - The occurrence of postoperative complications after various orthognatic surgery
      procedures is rare but all of them might be life-threatening complications. We
      report a case of a 22-year old female patient who underwent a bimaxillary
      orthognathic surgery procedure and developed bilateral pneumothorax and
      pneumomediastinum.

PMID- 24742426
TI  - Intermesenteric appendicular abscess, a diagnostic challenge; case report and
      review.
AB  - The appendicular origin of an intermesenteric abscess is rarely suspected prior
      to surgery, due to atypical clinical presentation and poor sensitivity of
      exploratory methods. A 43-year-old male was admitted for recent pain and mild
      tenderness in the epigastrium, slight emesis, leucocytosis (C-reactive protein
      was not determined), with no pathological findings on simple abdominal
      radiological examination (Rx). Abdominal ultrasound(US) and endoscopy were
      irrelevant. The abdomen became moderately tender, distended; diffuse enteric
      gas,slightly impaired bowel movement could be demonstrated by anew Rx. CT (oral
      contrast) was performed in the 3rd day:edematous infiltration of the mesentery
      and of a left-flank digestive loop (jejunal, sigmoidian?), small-size fluid
      collection(with extraluminal air-level) and paretic loops in the proximity, but
      normal wall-appearance of the caecum and its surrounding fat; the CT result was
      inconclusive (perforated diverticulosis or malignancy?). Barium enema:
      normal,including the caecum. Installation of vesperal fever, progressive mid
      abdominal pain, tenderness and formation of a mass were the rationale for open
      mid-line laparotomy, discovering a large intermesenteric abscess, secondary to
      perforated gangrenous intermesenteric appendicitis. Surgical outcome of
      appendectomy was normal. A high index of suspicion may be suggested by: atypical
      clinical presentation (fever; ileus;presence or formation of a tender,
      periumbilical, mass) and CT findings (abscess; extraluminal air; ileus).

PMID- 24742427
TI  - Cortical oscillations arise from contextual interactions that regulate sparse
      coding.
AB  - Precise spike times carry information and are important for synaptic plasticity.
      Synchronizing oscillations such as gamma bursts could coordinate spike times,
      thus regulating information transmission in the cortex. Oscillations are driven
      by inhibitory neurons and are modulated by sensory stimuli and behavioral states.
      How their power and frequency are regulated is an open question. Using a model
      cortical circuit, we propose a regulatory mechanism that depends on the activity
      balance of monosynaptic and disynaptic pathways to inhibitory neurons:
      Monosynaptic input causes more powerful oscillations whereas disynaptic input
      increases the frequency of oscillations. The balance of stimulation to the two
      pathways modulates the overall distribution of spikes, with stronger disynaptic
      stimulation (e.g., preferred stimuli inside visual receptive fields) producing
      high firing rates and weak oscillations; in contrast, stronger monosynaptic
      stimulation (e.g., suppressive contextual stimulation from outside visual
      receptive fields) generates low firing rates and strong oscillatory regulation of
      spike timing, as observed in alert cortex processing complex natural stimuli. By
      accounting for otherwise paradoxical experimental findings, our results
      demonstrate how the frequency and power of oscillations, and hence spike times,
      can be modulated by both sensory input and behavioral context, with powerful
      oscillations signifying a cortical state under inhibitory control in which spikes
      are sparse and spike timing is precise. 

PMID- 24742429
TI  - Funnel plot control limits to identify poorly performing healthcare providers
      when there is uncertainty in the value of the benchmark.
AB  - There is an increasing use of statistical methods, such as funnel plots, to
      identify poorly performing healthcare providers. Funnel plots comprise the
      construction of control limits around a benchmark and providers with outcomes
      falling outside the limits are investigated as potential outliers. The benchmark
      is usually estimated from observed data but uncertainty in this estimate is
      usually ignored when constructing control limits. In this paper, the use of
      funnel plots in the presence of uncertainty in the value of the benchmark is
      reviewed for outcomes from a Binomial distribution. Two methods to derive the
      control limits are shown: (i) prediction intervals; (ii) tolerance intervals
      Tolerance intervals formally include the uncertainty in the value of the
      benchmark while prediction intervals do not. The probability properties of 95%
      control limits derived using each method were investigated through hypothesised
      scenarios. Neither prediction intervals nor tolerance intervals produce funnel
      plot control limits that satisfy the nominal probability characteristics when
      there is uncertainty in the value of the benchmark. This is not necessarily to
      say that funnel plots have no role to play in healthcare, but that without the
      development of intervals satisfying the nominal probability characteristics they
      must be interpreted with care.

PMID- 24742428
TI  - Hassallidins, antifungal glycolipopeptides, are widespread among cyanobacteria
      and are the end-product of a nonribosomal pathway.
AB  - Cyanobacteria produce a wide variety of cyclic peptides, including the widespread
      hepatotoxins microcystins and nodularins. Another class of peptides, cyclic
      glycosylated lipopeptides called hassallidins, show antifungal activity.
      Previously, two hassallidins (A and B) were reported from an epilithic
      cyanobacterium Hassallia sp. and found to be active against opportunistic human
      pathogenic fungi. Bioinformatic analysis of the Anabaena sp. 90 genome identified
      a 59-kb cryptic inactive nonribosomal peptide synthetase gene cluster proposed to
      be responsible for hassallidin biosynthesis. Here we describe the hassallidin
      biosynthetic pathway from Anabaena sp. SYKE748A, as well as the large chemical
      variation and common occurrence of hassallidins in filamentous cyanobacteria.
      Analysis demonstrated that 20 strains of the genus Anabaena carry hassallidin
      synthetase genes and produce a multitude of hassallidin variants that exhibit
      activity against Candida albicans. The compounds discovered here were distinct
      from previously reported hassallidins A and B. The IC50 of hassallidin D was 0.29
      1.0 uM against Candida strains. A large variation in amino acids, sugars, their
      degree of acetylation, and fatty acid side chain length was detected. In
      addition, hassallidins were detected in other cyanobacteria including
      Aphanizomenon, Cylindrospermopsis raciborskii, Nostoc, and Tolypothrix. These
      compounds may protect some of the most important bloom-forming and globally
      distributed cyanobacteria against attacks by parasitic fungi. 

PMID- 24742430
TI  - Penalized count data regression with application to hospital stay after pediatric
      cardiac surgery.
AB  - Pediatric cardiac surgery may lead to poor outcomes such as acute kidney injury
      (AKI) and prolonged hospital length of stay (LOS). Plasma and urine biomarkers
      may help with early identification and prediction of these adverse clinical
      outcomes. In a recent multi-center study, 311 children undergoing cardiac surgery
      were enrolled to evaluate multiple biomarkers for diagnosis and prognosis of AKI
      and other clinical outcomes. LOS is often analyzed as count data, thus Poisson
      regression and negative binomial (NB) regression are common choices for
      developing predictive models. With many correlated prognostic factors and
      biomarkers, variable selection is an important step. The present paper proposes
      new variable selection methods for Poisson and NB regression. We evaluated
      regularized regression through penalized likelihood function. We first extend the
      elastic net (Enet) Poisson to two penalized Poisson regression: Mnet, a
      combination of minimax concave and ridge penalties; and Snet, a combination of
      smoothly clipped absolute deviation (SCAD) and ridge penalties. Furthermore, we
      extend the above methods to the penalized NB regression. For the Enet, Mnet, and
      Snet penalties (EMSnet), we develop a unified algorithm to estimate the
      parameters and conduct variable selection simultaneously. Simulation studies show
      that the proposed methods have advantages with highly correlated predictors,
      against some of the competing methods. Applying the proposed methods to the
      aforementioned data, it is discovered that early postoperative urine biomarkers
      including NGAL, IL18, and KIM-1 independently predict LOS, after adjusting for
      risk and biomarker variables.

PMID- 24742431
TI  - Construction of brewing-wine Aspergillus oryzae pyrG- mutant by pyrG gene
      deletion and its application in homology transformation.
AB  - pyrG(-) host cells are indispensable for pyrG(-) based transformation system.
      Isolations of pyrG(-) host cells by random mutations are limited by time
      consuming, unclear genetic background and potential interferences of homogenous
      recombination. The purpose of this study was to construct brewing-wine
      Aspergillus oryzae pyrG(-) mutant by site-directed mutation of pyrG gene deletion
      which would be used as a host for further transformation. pMD-pyrGAB, a vector
      carrying pyrG deletion cassette, was used to construct pyrG(-) mutant of A.
      oryzae. Three stable pyrG deletion mutants of A. oryzae were isolated by
      resistant to 5-fluoroorotic acid and confirmed by polymerase chain reaction
      analysis, indicating that pyrG was completely excised. The DeltapyrG mutants were
      applied as pyrG(-) host cells to disrupt xdh gene encoding xylitol dehydrogenase,
      which involves in xylitol production of A. oryzae. The xdh disruption mutants
      were efficiently constructed by transforming a pMD-pyrG-xdh disruption plasmid
      carrying pyrG, and the produced xylitol concentration of the Deltaxdh mutant was
      three times as much as that of the DeltapyrG recipient. Site-directed pyrG gene
      deletion is thus an effective way for the isolation of pyrG(-) host cells, and
      the established host-vector system could be applied in further functional
      genomics analysis and molecular breeding of A. oryzae.

PMID- 24742432
TI  - Target genes involved in antiproliferative effect of modified ginseng extracts in
      lung cancer A549 cells.
AB  - Lung cancer is the most common cancer and the leading cause of cancer-related
      deaths. Panax ginseng has long been used to treat cancer and other diseases
      worldwide. Most of the pharmacological actions of ginseng are attributed to a
      variety of ginsenosides, which are often metabolized by intestinal bacteria into
      more effective forms. In this study, we found that the antiproliferative activity
      of ginseng was increased after enzymatic processing of ginseng saponin (50%
      inhibitory concentration, >70 MUg/ml). To elucidate the mechanism by which
      modified ginseng extract (MGX) induced cell death in human lung cancer cells, the
      gene expression profiles of A549 cells regulated by MGX were assayed using
      Agilent PrimeView Human Gene Expression Arrays. The expression of 17 genes
      involved in the regulation of cell signaling, cell metabolism, transport, and
      cytoskeleton-regulation was up-regulated, whereas the expression of 16 genes
      implicated in invasion and metastasis and cellular metabolism was down-regulated
      in MGX-treated A549 cells. Moreover, nuclear staining with 4',6-diamidino-2
      phenylindole revealed that MGX clearly caused nuclear condensation and
      fragmentation which are observed in apoptosis cell. These results elucidate
      crucial anticancer mechanisms of MGX and provide potential new targets for the
      assessment of anticancer activity of MGX.

PMID- 24742450
TI  - Current management strategies for systemic sclerosis.
AB  - Systemic sclerosis remains a challenging disease despite progress that has taken
      place in the management of organ-based complications. Overall management
      strategies need to take into account the features of the disease that are common
      to almost all patients such as skin involvement, gastro-oesophageal
      manifestations and secondary Raynaud's, as well as identify less frequent but
      critical manifestations that impact on survival including heart, lung, renal and
      more severe GI involvement. Treatments can be considered to be disease-modifying
      or symptomatic. In addition, it is important to address more generic problems
      such as the emotional, psychological and economic impact of a chronic autoimmune
      rheumatic disease. This article reviews general approaches to disease assessment
      and management and relates this to subset and stage of the condition. 

PMID- 24742451
TI  - Targeted immunotherapies in systemic sclerosis.
AB  - Systemic sclerosis (SSc) is a heterogeneous systemic disorder characterised by
      alterations of the microvasculature, disturbances of the immune system and
      massive deposition of collagen and other matrix substances in connective tissue.
      Recent genetic studies have underlined the importance of the autoimmune component
      of the disease. Biologic therapies target molecules involved in the mechanisms of
      the immune system, such as cytokines (TNF-alpha, IL-6), immune cells (B cells) or
      co-stimulation molecules (CTLA4), and are currently used in several autoimmune
      rheumatic diseases, in particular rheumatoid arthritis. These drugs provide an
      alternative to the existing treatment methods of disease-modifying anti-rheumatic
      drugs and other immunosuppressive medications. Since some of the molecules
      targeted by biologic therapies are known to contribute to fibrosis in vitro or in
      animal models of experimental fibrosis, and considering that preliminary data are
      now available regarding the efficacy and safety of targeted immunotherapies in
      SSc, we aim to report with this review the results obtained in animals and humans
      for the biotherapies that have already been developed. 

PMID- 24742452
TI  - Muscle matters in Kennedy's disease.
AB  - Polyglutamine expansion in the androgen receptor causes Kennedy's disease. Two
      recent reports, Cortes et al. (2014) in this issue of Neuron and Lieberman et al.
      (2014) in Cell Reports, raise the possibility that targeting expression of the
      mutant protein in skeletal muscle, instead of the nervous system, may mitigate
      manifestations of this disorder. 

PMID- 24742453
TI  - Hidden progenitors replace microglia in the adult brain.
AB  - Microglia are highly dynamic components of the innate immune system. In this
      issue of Neuron, Elmore et al. (2014) report that global depletion of microglia
      triggers mobilization of latent microglial progenitors throughout the CNS,
      resulting in rapid repopulation. 

PMID- 24742454
TI  - How to grow a synapse.
AB  - Activity-dependent alterations in the strength of an individual glutamatergic
      synapse are often accompanied by changes in the size and shape of the
      postsynaptic terminal. Two studies in this issue of Neuron, Meyer et al. (2014)
      and Bosch et al. (2014), shed new light on the mechanisms and signaling pathways
      underlying structural long-term potentiation. 

PMID- 24742455
TI  - The vacuum shouts back: postpublication peer review on social media.
AB  - Social media has created new pathways for postpublication peer review, which
      regularly leads to corrections. Such online discussions are often resisted by
      authors and editors, however, and efforts to formalize postpublication peer
      review have not yet resonated with scientific communities. 

PMID- 24742457
TI  - Extrasynaptic NMDA receptor involvement in central nervous system disorders.
AB  - NMDA receptor (NMDAR)-induced excitotoxicity is thought to contribute to the cell
      death associated with certain neurodegenerative diseases, stroke, epilepsy, and
      traumatic brain injury. Targeting NMDARs therapeutically is complicated by the
      fact that cell signaling downstream of their activation can promote cell survival
      and plasticity as well as excitotoxicity. However, research over the past decade
      has suggested that overactivation of NMDARs located outside of the synapse plays
      a major role in NMDAR toxicity, whereas physiological activation of those inside
      the synapse can contribute to cell survival, raising the possibility of
      therapeutic intervention based on NMDAR subcellular localization. Here, we review
      the evidence both supporting and refuting this localization hypothesis of NMDAR
      function and discuss the role of NMDAR localization in disorders of the nervous
      system. Preventing excessive extrasynaptic NMDAR activation may provide
      therapeutic benefit, particularly in Alzheimer disease and Huntington disease. 

PMID- 24742456
TI  - Representing sex in the brain, one module at a time.
AB  - Sexually dimorphic behaviors, qualitative or quantitative differences in
      behaviors between the sexes, result from the activity of a sexually
      differentiated nervous system. Sensory cues and sex hormones control the entire
      repertoire of sexually dimorphic behaviors, including those commonly thought to
      be charged with emotion such as courtship and aggression. Such overarching
      control mechanisms regulate distinct genes and neurons that in turn specify the
      display of these behaviors in a modular manner. How such modular control is
      transformed into cohesive internal states that correspond to sexually dimorphic
      behavior is poorly understood. We summarize current understanding of the neural
      circuit control of sexually dimorphic behaviors from several perspectives,
      including how neural circuits in general, and sexually dimorphic neurons in
      particular, can generate sexually dimorphic behaviors, and how molecular
      mechanisms and evolutionary constraints shape these behaviors. We propose that
      emergent themes such as the modular genetic and neural control of dimorphic
      behavior are broadly applicable to the neural control of other behaviors. 

PMID- 24742458
TI  - Muscle expression of mutant androgen receptor accounts for systemic and motor
      neuron disease phenotypes in spinal and bulbar muscular atrophy.
AB  - X-linked spinal and bulbar muscular atrophy (SBMA) is characterized by adult
      onset muscle weakness and lower motor neuron degeneration. SBMA is caused by CAG
      polyglutamine (polyQ) repeat expansions in the androgen receptor (AR) gene.
      Pathological findings include motor neuron loss, with polyQ-AR accumulation in
      intranuclear inclusions. SBMA patients exhibit myopathic features, suggesting a
      role for muscle in disease pathogenesis. To determine the contribution of muscle,
      we developed a BAC mouse model featuring a floxed first exon to permit cell-type
      specific excision of human AR121Q. BAC fxAR121 mice develop systemic and
      neuromuscular phenotypes, including shortened survival. After validating
      termination of AR121 expression and full rescue with ubiquitous Cre, we crossed
      BAC fxAR121 mice with Human Skeletal Actin-Cre mice. Muscle-specific excision
      prevented weight loss, motor phenotypes, muscle pathology, and motor neuronopathy
      and dramatically extended survival. Our results reveal a crucial role for muscle
      expression of polyQ-AR in SBMA and suggest muscle-directed therapies as effective
      treatments. 

PMID- 24742459
TI  - Sequential axon-derived signals couple target survival and layer specificity in
      the Drosophila visual system.
AB  - Neural circuit formation relies on interactions between axons and cells within
      the target field. While it is well established that target-derived signals act on
      axons to regulate circuit assembly, the extent to which axon-derived signals
      control circuit formation is not known. In the Drosophila visual system,
      anterograde signals numerically match R1-R6 photoreceptors with their targets by
      controlling target proliferation and neuronal differentiation. Here we
      demonstrate that additional axon-derived signals selectively couple target
      survival with layer specificity. We show that Jelly belly (Jeb) produced by R1-R6
      axons interacts with its receptor, anaplastic lymphoma kinase (Alk), on budding
      dendrites to control survival of L3 neurons, one of three postsynaptic targets.
      L3 axons then produce Netrin, which regulates the layer-specific targeting of
      another neuron within the same circuit. We propose that a cascade of axon-derived
      signals, regulating diverse cellular processes, provides a strategy for
      coordinating circuit assembly across different regions of the nervous system. 

PMID- 24742460
TI  - Lhx6 directly regulates Arx and CXCR7 to determine cortical interneuron fate and
      laminar position.
AB  - Cortical GABAergic interneurons have essential roles for information processing
      and their dysfunction is implicated in neuropsychiatric disorders.
      Transcriptional codes are elucidating mechanisms of interneuron specification in
      the MGE (a subcortical progenitor zone), which regulate their migration,
      integration, and function within cortical circuitry. Lhx6, a LIM-homeodomain
      transcription factor, is essential for specification of MGE-derived somatostatin
      and parvalbumin interneurons. Here, we demonstrate that some Lhx6-/- MGE cells
      acquire a CGE-like fate. Using an in vivo MGE complementation/transplantation
      assay, we show that Lhx6-regulated genes Arx and CXCR7 rescue divergent aspects
      of Lhx6-/- cell-fate and laminar mutant phenotypes and provide insight into a
      neonatal role for CXCR7 in MGE-derived interneuron lamination. Finally, Lhx6
      directly binds in vivo to an Arx enhancer and to an intronic CXCR7 enhancer that
      remains active in mature interneurons. These data define the molecular identity
      of Lhx6 mutants and introduce technologies to test mechanisms in GABAergic
      interneuron differentiation.

PMID- 24742461
TI  - Colony-stimulating factor 1 receptor signaling is necessary for microglia
      viability, unmasking a microglia progenitor cell in the adult brain.
AB  - The colony-stimulating factor 1 receptor (CSF1R) is a key regulator of myeloid
      lineage cells. Genetic loss of the CSF1R blocks the normal population of resident
      microglia in the brain that originates from the yolk sac during early
      development. However, the role of CSF1R signaling in microglial homeostasis in
      the adult brain is largely unknown. To this end, we tested the effects of
      selective CSF1R inhibitors on microglia in adult mice. Surprisingly, extensive
      treatment results in elimination of ~99% of all microglia brain-wide, showing
      that microglia in the adult brain are physiologically dependent upon CSF1R
      signaling. Mice depleted of microglia show no behavioral or cognitive
      abnormalities, revealing that microglia are not necessary for these tasks.
      Finally, we discovered that the microglia-depleted brain completely repopulates
      with new microglia within 1 week of inhibitor cessation. Microglial repopulation
      throughout the CNS occurs through proliferation of nestin-positive cells that
      then differentiate into microglia.

PMID- 24742462
TI  - Selective memory generalization by spatial patterning of protein synthesis.
AB  - Protein synthesis is crucial for both persistent synaptic plasticity and long
      term memory. De novo protein expression can be restricted to specific neurons
      within a population, and to specific dendrites within a single neuron. Despite
      its ubiquity, the functional benefits of spatial protein regulation for learning
      are unknown. We used computational modeling to study this problem. We found that
      spatially patterned protein synthesis can enable selective consolidation of some
      memories but forgetting of others, even for simultaneous events that are
      represented by the same neural population. Key factors regulating selectivity
      include the functional clustering of synapses on dendrites, and the sparsity and
      overlap of neural activity patterns at the circuit level. Based on these
      findings, we proposed a two-step model for selective memory generalization during
      REM and slow-wave sleep. The pattern-matching framework we propose may be broadly
      applicable to spatial protein signaling throughout cortex and hippocampus. 

PMID- 24742463
TI  - Conditions and constraints for astrocyte calcium signaling in the hippocampal
      mossy fiber pathway.
AB  - The spatiotemporal activities of astrocyte Ca2+ signaling in mature neuronal
      circuits remain unclear. We used genetically encoded Ca2+ and glutamate
      indicators as well as pharmacogenetic and electrical control of neurotransmitter
      release to explore astrocyte activity in the hippocampal mossy fiber pathway. Our
      data revealed numerous localized, spontaneous Ca2+ signals in astrocyte branches
      and territories, but these were not driven by neuronal activity or glutamate.
      Moreover, evoked astrocyte Ca2+ signaling changed linearly with the number of
      mossy fiber action potentials. Under these settings, astrocyte responses were
      global, suppressed by neurotransmitter clearance, and mediated by glutamate and
      GABA. Thus, astrocyte engagement in the fully developed mossy fiber pathway was
      slow and territorial, contrary to that frequently proposed for astrocytes within
      microcircuits. We show that astrocyte Ca2+ signaling functionally segregates
      large volumes of neuropil and that these transients are not suited for responding
      to, or regulating, single synapses in the mossy fiber pathway.

PMID- 24742464
TI  - Balance and stability of synaptic structures during synaptic plasticity.
AB  - Subsynaptic structures such as bouton, active zone, postsynaptic density (PSD)
      and dendritic spine, are highly correlated in their dimensions and also correlate
      with synapse strength. Why this is so and how such correlations are maintained
      during synaptic plasticity remains poorly understood. We induced spine
      enlargement by two-photon glutamate uncaging and examined the relationship
      between spine, PSD, and bouton size by two-photon time-lapse imaging and electron
      microscopy. In enlarged spines the PSD-associated protein Homer1c increased
      rapidly, whereas the PSD protein PSD-95 increased with a delay and only in cases
      of persistent spine enlargement. In the case of nonpersistent spine enlargement,
      the PSD proteins remained unchanged or returned to their original level. The
      ultrastructure at persistently enlarged spines displayed matching dimensions of
      spine, PSD, and bouton, indicating their correlated enlargement. This supports a
      model in which balancing of synaptic structures is a hallmark for the
      stabilization of structural modifications during synaptic plasticity. 

PMID- 24742465
TI  - Structural and molecular remodeling of dendritic spine substructures during long
      term potentiation.
AB  - Synapses store information by long-lasting modifications of their structure and
      molecular composition, but the precise chronology of these changes has not been
      studied at single-synapse resolution in real time. Here we describe the
      spatiotemporal reorganization of postsynaptic substructures during long-term
      potentiation (LTP) at individual dendritic spines. Proteins translocated to the
      spine in four distinct patterns through three sequential phases. In the initial
      phase, the actin cytoskeleton was rapidly remodeled while active cofilin was
      massively transported to the spine. In the stabilization phase, cofilin formed a
      stable complex with F-actin, was persistently retained at the spine, and
      consolidated spine expansion. In contrast, the postsynaptic density (PSD) was
      independently remodeled, as PSD scaffolding proteins did not change their amount
      and localization until a late protein synthesis-dependent third phase. Our
      findings show how and when spine substructures are remodeled during LTP and
      explain why synaptic plasticity rules change over time. 

PMID- 24742468
TI  - Identifying mechanisms of change: utilizing single-participant methodology to
      better understand behavior therapy for child depression.
AB  - This study examined therapeutic mechanisms of action at the single-participant
      level in a behavior therapy (BT) for youth depression. By controlling for non
      specific early responses, identifying potential mechanisms of action a priori,
      taking frequent measures of hypothesized mechanisms and dependent variables,
      rigorously evaluating internal validity, and using a variety of analytic methods,
      a unique model for analysis of potential mediators was created. Eleven children
      (M age = 9.84) meeting criteria on the Children's Depression Rating Scale-Revised
      (M = 55.36) and Children's Depression Inventory (M = 23.45) received non
      directive therapy (NDT), followed by BT for those still displaying significant
      symptoms. Four participants (36%) had a clinically significant response to NDT.
      For the remaining seven, statistically significant changes in depressive symptoms
      and family interactions during the BT interval were found at the group level. At
      the single-participant level, evidence suggesting that outcome was at least
      partially mediated by changes in treatment targets was obtained for four of seven
      (57%). As the field further embraces efforts to learn not only whether treatments
      work but also how they work, the single-participant approach to evaluating
      mediators provides a useful framework for evaluating theories of therapeutic
      change. 

PMID- 24742466
TI  - The synaptic and circuit mechanisms underlying a change in spatial encoding in
      the retina.
AB  - Components of neural circuits are often repurposed so that the same biological
      hardware can be used for distinct computations. This flexibility in circuit
      operation is required to account for the changes in sensory computations that
      accompany changes in input signals. Yet we know little about how such changes in
      circuit operation are implemented. Here we show that a single retinal ganglion
      cell performs a different computation in dim light--averaging contrast within its
      receptive field--than in brighter light, when the cell becomes sensitive to fine
      spatial detail. This computational change depends on interactions between two
      parallel circuits that control the ganglion cell's excitatory synaptic inputs.
      Specifically, steady-state interactions through dendro-axonal gap junctions
      control rectification of the synapses providing excitatory input to the ganglion
      cell. These findings provide a clear example of how a simple synaptic mechanism
      can repurpose a neural circuit to perform diverse computations.

PMID- 24742467
TI  - Emergent selectivity for task-relevant stimuli in higher-order auditory cortex.
AB  - A variety of attention-related effects have been demonstrated in primary auditory
      cortex (A1). However, an understanding of the functional role of higher auditory
      cortical areas in guiding attention to acoustic stimuli has been elusive. We
      recorded from neurons in two tonotopic cortical belt areas in the dorsal
      posterior ectosylvian gyrus (dPEG) of ferrets trained on a simple auditory
      discrimination task. Neurons in dPEG showed similar basic auditory tuning
      properties to A1, but during behavior we observed marked differences between
      these areas. In the belt areas, changes in neuronal firing rate and response
      dynamics greatly enhanced responses to target stimuli relative to distractors,
      allowing for greater attentional selection during active listening. Consistent
      with existing anatomical evidence, the pattern of sensory tuning and behavioral
      modulation in auditory belt cortex links the spectrotemporal representation of
      the whole acoustic scene in A1 to a more abstracted representation of task
      relevant stimuli observed in frontal cortex. 

PMID- 24742469
TI  - Extra virgin olive oil phenols down-regulate lipid synthesis in primary-cultured
      rat-hepatocytes.
AB  - Hydroxytyrosol, tyrosol, and oleuropein, the main phenols present in extra virgin
      olive oil, have been reported to exert several biochemical and pharmacological
      effects. Here, we investigated the short-term effects of these compounds on lipid
      synthesis in primary-cultured rat-liver cells. Hydroxytyrosol, tyrosol and
      oleuropein inhibited both de novo fatty acid and cholesterol syntheses without an
      effect on cell viability. The inhibitory effect of individual compounds was
      already evident within 2 h of 25 MUM phenol addition to the hepatocytes. The
      degree of cholesterogenesis reduction was similar for all phenol treatments (
      25/30%), while fatty acid synthesis showed the following order of inhibition:
      hydroxytyrosol (-49%) = oleuropein (-48%) > tyrosol (-30%). A phenol-induced
      reduction of triglyceride synthesis was also detected. To clarify the lipid
      lowering mechanism of these compounds, their influence on the activity of key
      enzymes of fatty acid biosynthesis (acetyl-CoA carboxylase and fatty acid
      synthase), triglyceride synthesis (diacylglycerol acyltransferase) and
      cholesterogenesis (3-hydroxy-3-methyl-glutaryl-CoA reductase) was investigated in
      situ by using digitonin-permeabilized hepatocytes. Acetyl-CoA carboxylase,
      diacylglycerol acyltransferase and 3-hydroxy-3-methyl-glutaryl-CoA reductase
      activities were reduced after 2 h of 25 MUM phenol treatment. No change in fatty
      acid synthase activity was observed. Acetyl-CoA carboxylase inhibition
      (hydroxytyrosol, -41%, = oleuropein, -38%, > tyrosol, -17%) appears to be
      mediated by phosphorylation of AMP-activated protein kinase. These findings
      suggest that a decrease in hepatic lipid synthesis may represent a potential
      mechanism underlying the reported hypolipidemic effect of phenols of extra virgin
      olive oil. 

PMID- 24742472
TI  - Comparison of in-hospital outcomes for beta-blocker use versus non-beta blocker
      use in patients presenting with cocaine-associated chest pain.
AB  - Beta blockers are indicated for management of acute coronary syndromes, but they
      generally are withheld in patients with cocaine-associated chest pain because of
      concerns for adverse outcomes related to the unique physiological effects of
      cocaine. Because few clinical studies have evaluated this interaction, we
      identified patients with toxicology screen results positive for cocaine treated
      for chest pain at 2 academic hospitals. Clinical characteristics and in-hospital
      outcomes were compared between patients with and without beta-blocker therapy. We
      then constructed propensity scores to evaluate the independent relation between
      beta-blocker use and the composite primary end point of myocardial infarction,
      stroke, ventricular arrhythmia, or all-cause mortality after adjusting for
      clinical characteristics. Of 376 consecutive patients with cocaine-related chest
      pain, beta blockers were used in 164 (44%). Compared with no beta blockers,
      patients treated with beta blockers were more likely to describe anginal chest
      pain, to have known cardiovascular risk factors, and to receive other
      antiatherosclerotic therapies. Despite these higher risk clinical
      characteristics, patients treated with beta blockers experienced similar peak
      troponin levels, individual adverse events, and rates of the composite primary
      end point (15.9% vs 12.3%, p = 0.32). The primary end point also was similar
      after propensity score analysis (odds ratio 1.37, 95% confidence interval 0.64 to
      2.93, p = 0.42), including specific comparisons of beta-1 selective (odds ratio
      1.83, 95% confidence interval 0.79 to 4.24) and nonselective (odds ratio 0.90,
      95% confidence interval 0.33 to 2.42) beta blockers, when compared with patients
      not receiving beta blockers. In conclusion, no differences in outcomes were
      observed between patients treated versus not treated with beta-blocker therapy in
      the setting of cocaine-related chest pain.

PMID- 24742471
TI  - Insight into the impact of dietary saturated fat on tissue-specific cellular
      processes underlying obesity-related diseases.
AB  - This study investigated the influence of three high-fat diets (HFDs), differing
      in the percentage of total calories from saturated fat (SF) (6%, 12%, 24%) but
      identical in total fat (40%), for a 16-week period in mice on a variety of tissue
      specific cellular processes believed to be at the root of obesity-related
      diseases. Specifically, we examined ectopic lipid accumulation, oxidative
      capacity [peroxisome proliferator-activated receptor gamma coactivator 1-alpha
      (PGC-1alpha) mRNA and protein; mtDNA; Cox IV and cytochrome C protein; citrate
      synthase activity; and gene expression of fission 1, mitofusin (Mfn) 1 and Mfn2],
      oxidative stress (4-hydroxy-2-nonenal), endoplasmic reticulum (ER) stress
      (binding immunoglobulin protein, activating transcription factor 6-p50, p
      eukaryotic initiation factor 2 alpha and x-box binding protein 1 spliced
      protein), inflammatory [p-c-Jun N-terminal kinase (JNK), p-nuclear factor kappa
      B, p-p38 mitogen-activated protein kinase) and insulin signaling (p-Akt), and
      inflammation [tumor necrosis factor-alpha, monocyte chemotactic protein-1,
      interleukin-6, F4/80, toll-like receptor (TLR)2 and TLR4 gene expression] in
      various tissues, including the adipose tissue, liver, skeletal muscle and heart.
      In general, adipose and hepatic tissues were the only tissues which displayed
      evidence of dysfunction. All HFDs down-regulated adipose, cardiac and hepatic PGC
      1alpha mRNA and hepatic citrate synthase activity, and induced adipose tissue
      oxidative stress, whereas only the 6%-SF and 12%-SF diet produced hepatic
      steatosis. However, compared to the 6%-SF and 24%-SF diets, consumption of the
      12%-SF diet resulted in the greatest degree of dysregulation (hepatic ER and
      oxidative stress, JNK activation, increased F4/80 gene expression and down
      regulation of adipose tissue Akt signaling). These findings suggest that the
      saturated fatty acid composition of an HFD can greatly influence the processes
      responsible for obesity-related diseases - nonalcoholic fatty liver disease, in
      particular - as well as provide further evidence that the mechanisms at the root
      of these diseases are diet and tissue sensitive. 

PMID- 24742470
TI  - Dietary antiaging phytochemicals and mechanisms associated with prolonged
      survival.
AB  - Aging is well-known an inevitable process that is influenced by genetic,
      lifestyle and environmental factors. However, the exact mechanisms underlying the
      aging process are not well understood. Increasing evidence shows that aging is
      highly associated with chronic increase in reactive oxygen species (ROS),
      accumulation of a low-grade proinflammatory phenotype and reduction in age
      related autophagy, suggesting that these factors may play important roles in
      promoting aging. Indeed, reduction of ROS and low-grade inflammation and
      promotion of autophagy by calorie restriction or other dietary manipulation can
      extend lifespan in a wide spectrum of model organisms. Interestingly, recent
      studies show that some food-derived small molecules, also called phytochemicals,
      can extend lifespan in various animal species. In this paper, we review several
      recently identified potential antiaging phytochemicals that have been studied in
      cells, animals and humans and further highlight the cellular and molecular
      mechanisms underlying the antiaging actions by these molecules. 

PMID- 24742473
TI  - PLAB and UK graduates' performance on MRCP(UK) and MRCGP examinations: data
      linkage study.
AB  - OBJECTIVES: To assess whether international medical graduates passing the two
      examinations set by the Professional and Linguistic Assessments Board (PLAB1 and
      PLAB2) of the General Medical Council (GMC) are equivalent to UK graduates at the
      end of the first foundation year of medical training (F1), as the GMC requires,
      and if not, to assess what changes in the PLAB pass marks might produce
      equivalence. DESIGN: Data linkage of GMC PLAB performance data with data from the
      Royal Colleges of Physicians and the Royal College of General Practitioners on
      performance of PLAB graduates and UK graduates at the MRCP(UK) and MRCGP
      examinations. SETTING: Doctors in training for internal medicine or general
      practice in the United Kingdom. PARTICIPANTS: 7829, 5135, and 4387 PLAB graduates
      on their first attempt at MRCP(UK) Part 1, Part 2, and PACES assessments from
      2001 to 2012 compared with 18,532, 14,094, and 14,376 UK graduates taking the
      same assessments; 3160 PLAB1 graduates making their first attempt at the MRCGP
      AKT during 2007-12 compared with 14,235 UK graduates; and 1411 PLAB2 graduates
      making their first attempt at the MRCGP CSA during 2010-12 compared with 6935 UK
      graduates. MAIN OUTCOME MEASURES: Performance at MRCP(UK) Part 1, Part 2, and
      PACES assessments, and MRCGP AKT and CSA assessments in relation to performance
      on PLAB1 and PLAB2 assessments, as well as to International English Language
      Testing System (IELTS) scores. MRCP(UK), MRCGP, and PLAB results were analysed as
      marks relative to the pass mark at the first attempt. RESULTS: PLAB1 marks were a
      valid predictor of MRCP(UK) Part 1, MRCP(UK) Part 2, and MRCGP AKT (r=0.521,
      0.390, and 0.490; all P<0.001). PLAB2 marks correlated with MRCP(UK) PACES and
      MRCGP CSA (r=0.274, 0.321; both P<0.001). PLAB graduates had significantly lower
      MRCP(UK) and MRCGP assessments (Glass's Delta=0.94, 0.91, 1.40, 1.01, and 1.82
      for MRCP(UK) Part 1, Part 2, and PACES and MRCGP AKT and CSA), and were more
      likely to fail assessments and to progress more slowly than UK medical graduates.
      IELTS scores correlated significantly with later performance, multiple regression
      showing that the effect of PLAB1 (beta=0.496) was much stronger than the effect
      of IELTS (beta=0.086). Changes to PLAB pass marks that would result in
      international medical graduate and UK medical graduate equivalence were assessed
      in two ways. Method 1 adjusted PLAB pass marks to equate median performance of
      PLAB and UK graduates. Method 2 divided PLAB graduates into 12 equally spaced
      groups according to PLAB performance, and compared these with mean performance of
      graduates from individual UK medical schools, assessing which PLAB groups were
      equivalent in MRCP(UK) and MRCGP performance to UK graduates. The two methods
      produced similar results. To produce equivalent performance on the MRCP and MRGP
      examinations, the pass mark for PLAB1 would require raising by about 27 marks
      (13%) and for PLAB2 by about 15-16 marks (20%) above the present standard.
      CONCLUSIONS: PLAB is a valid assessment of medical knowledge and clinical skills,
      correlating well with performance at MRCP(UK) and MRCGP. PLAB graduates'
      knowledge and skills at MRCP(UK) and MRCGP are over one standard deviation below
      those of UK graduates, although differences in training quality cannot be taken
      into account. Equivalent performance in MRCGP(UK) and MRCGP would occur if the
      pass marks of PLAB1 and PLAB2 were raised considerably, but that would also
      reduce the pass rate, with implications for medical workforce planning.
      Increasing IELTS requirements would have less impact on equivalence than raising
      PLAB pass marks.

PMID- 24742474
TI  - American Society of Nephrology Quiz and Questionnaire 2013: transplantation.
AB  - The nephrology quiz and questionnaire remains an extremely popular session for
      attendees of the Annual Meeting of the American Society of Nephrology. As in past
      years, the conference hall was overflowing with interested audience members.
      Topics covered by expert discussants included electrolyte and acid-base
      disorders, glomerular disease, ESRD/dialysis, and transplantation. Complex cases
      representing each of these categories along with single best answer questions
      were prepared by a panel of experts. Before the meeting, program directors of
      United States nephrology training programs answered questions through an Internet
      based questionnaire. A new addition to the nephrology quiz and questionnaire was
      participation in the questionnaire by nephrology fellows. To review the process,
      members of the audience test their knowledge and judgment on a series of case
      oriented questions prepared and discussed by experts. Their answers are compared
      in real time using audience response devices with the answers of nephrology
      fellows and training program directors. The correct and incorrect answers are
      then briefly discussed after the audience responds, and the results of the
      questionnaire are displayed. This article recapitulates the session and
      reproduces its educational value for the readers of CJASN. Enjoy the clinical
      cases and expert discussions.

PMID- 24742476
TI  - BMI, sex, and access to transplantation.

PMID- 24742475
TI  - Control of urinary drainage and voiding.
AB  - Urine differs greatly in ion and solute composition from plasma and contains
      harmful and noxious substances that must be stored for hours and then eliminated
      when it is socially convenient to do so. The urinary tract that handles this
      output is composed of a series of pressurizable muscular compartments separated
      by sphincteric structures. With neural input, these structures coordinate the
      delivery, collection, and, ultimately, expulsion of urine. Despite large osmotic
      and chemical gradients in this waste fluid, the bladder maintains a highly
      impermeable surface in the face of a physically demanding biomechanical
      environment, which mandates recurring cycles of surface area expansion and
      increased wall tension during filling, followed by rapid wall compression during
      voiding. Afferent neuronal inflow from mucosa and submucosa communicates sensory
      information about bladder fullness, and voiding is initiated consciously through
      coordinated central and spinal efferent outflow to the detrusor, trigonal
      internal sphincter, and external urethral sphincter after periods of relative
      quiescence. Provocative new findings suggest that in some cases, lower urinary
      tract symptoms, such as incontinence, urgency, frequency, overactivity, and pain
      may be viewed as a consequence of urothelial defects (either urothelial barrier
      breakdown or inappropriate signaling from urothelial cells to underlying sensory
      afferents and potentially interstitial cells). This review describes the
      physiologic and anatomic mechanisms by which urine is moved from the kidney to
      the bladder, stored, and then released. Relevant clinical examples of urinary
      tract dysfunction are also discussed. 

PMID- 24742478
TI  - Differential association of body mass index with access to kidney transplantation
      in men and women.
AB  - BACKGROUND AND OBJECTIVES: Obese patients encounter barriers to medical care not
      encountered by lean patients, and inequities in access to care among obese
      patients may vary by sex. This study aimed to determine the association of body
      mass index (BMI) with access to kidney transplantation in men and women. DESIGN,
      SETTING, PARTICIPANTS, & MEASUREMENTS: In this retrospective analysis of 702,456
      incident ESRD patients aged 18-70 years (captured in the US Renal Data System
      between 1995 and 2007), multivariate time-to-event analyses were used to
      determine the association of BMI with likelihood of transplantation from any
      donor source, transplantation from a living donor, and transplantation from a
      deceased donor, as well the individual steps in obtaining a deceased donor
      transplant (activation to the waiting list, and transplantation after wait
      listing). RESULTS: Among women, a BMI >= 25.0 kg/m(2) was associated with a lower
      likelihood of transplantation from any donor source (hazard ratio [HR], 0.75; 95%
      confidence interval [95% CI], 0.73 to 0.77), transplantation from a living donor
      (HR, 0.75; 95% CI, 0.72 to 0.77), and transplantation from a deceased donor (HR,
      0.74; 95% CI, 0.72 to 0.77). By contrast, among men, a BMI of 25.0-34.9 kg/m(2)
      was associated with a higher likelihood of the outcomes of transplantation from
      any donor source (HR, 1.08; 95% CI, 1.06 to 1.11), transplantation from a living
      donor (HR, 1.18; 95% CI, 1.13 to 1.22), and transplantation from a deceased donor
      (HR, 1.05; 95% CI, 1.02 to 1.07). Among men, the level beyond which BMI was
      associated with a lower likelihood of transplantation from any donor source or a
      living donor was >= 40.0 kg/m(2), and >= 35.0 kg/m(2) in the case of deceased
      donor transplantation. CONCLUSIONS: The association of BMI with access to
      transplantation varies between men and women. The reasons for this difference
      should be further studied.

PMID- 24742477
TI  - Rapid detection of monogenic causes of childhood-onset steroid-resistant
      nephrotic syndrome.
AB  - BACKGROUND AND OBJECTIVES: In steroid-resistant nephrotic syndrome (SRNS), >21
      single-gene causes are known. However, mutation analysis of all known SRNS genes
      is time and cost intensive. This report describes a new high-throughput method of
      mutation analysis using a PCR-based microfluidic technology that allows rapid
      simultaneous mutation analysis of 21 single-gene causes of SRNS in a large number
      of individuals. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This study
      screened individuals with SRNS; samples were submitted for mutation analysis from
      international sources between 1996 and 2012. For proof of principle, a pilot
      cohort of 48 individuals who harbored known mutations in known SRNS genes was
      evaluated. After improvements to the method, 48 individuals with an unknown cause
      of SRNS were then examined in a subsequent diagnostic study. The analysis
      included 16 recessive SRNS genes and 5 dominant SRNS genes. A 10-fold primer
      multiplexing was applied, allowing PCR-based amplification of 474 amplicons in 21
      genes for 48 DNA samples simultaneously. Forty-eight individuals were indexed in
      a barcode PCR, and high-throughput sequencing was performed. All disease-causing
      variants were confirmed via Sanger sequencing. RESULTS: The pilot study
      identified the genetic cause of disease in 42 of 48 (87.5%) of the affected
      individuals. The diagnostic study detected the genetic cause of disease in 16 of
      48 (33%) of the affected individuals with a previously unknown cause of SRNS.
      Seven novel disease-causing mutations in PLCE1 (n=5), NPHS1 (n=1), and LAMB2
      (n=1) were identified in <3 weeks. Use of this method could reduce costs to
      1/29th of the cost of Sanger sequencing. CONCLUSION: This highly parallel
      approach allows rapid (<3 weeks) mutation analysis of 21 genes known to cause
      SRNS at a greatly reduced cost (1/29th) compared with traditional mutation
      analysis techniques. It detects mutations in about 33% of childhood-onset SRNS
      cases.

PMID- 24742479
TI  - Association of a polymorphism in a gene encoding a urate transporter with CKD
      progression.
AB  - BACKGROUND AND OBJECTIVES: Hyperuricemia predicts a high risk for CKD progression
      but there is no large clinical trial in humans indicating that this relationship
      is causal in nature. The rs734553 single-nucleotide polymorphism (SNP) of the
      GLUT9 urate transporter gene was strongly associated with uric acid (UA) levels
      in a large meta-analysis. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This
      prospective study adopted the Mendelian randomization approach. The rs734553 SNP
      was used as an instrumental variable to investigate the relationship between UA
      and renal outcomes in a cohort of 755 patients with CKD who were enrolled between
      October 18, 2005, and October 2, 2008. The association between the polymorphism
      and UA was preliminary confirmed in a series of 211 healthy volunteers enrolled
      between January 1, 2001, and July 12, 2011, from the same geographic area as the
      patients with CKD. The study end point was a composite renal-end point (i.e.,
      >30% decrease in the GFR, dialysis, or transplantation). Patients were followed
      up for a median of 36 months. RESULTS: In healthy individuals, serum UA levels
      were highest in homozygotes for the T allele (risk allele), intermediate in
      heterozygotes for the same allele, and lowest in those without the risk allele
      (P<0.001), but no such relationship was found in patients with CKD. In the CKD
      cohort, homozygotes (TT) and heterozygotes (GT) for the risk allele had a 2.35
      times higher risk (hazard ratio, 2.35; 95% confidence interval, 1.25 to 4.42;
      P=0.008) of CKD progression. The risk for CKD progression by rs734553 remained
      unmodified in analyses adjusting for proteinuria, GFR, and other classical and
      CKD-peculiar risk factors. CONCLUSIONS: A GLUT9 polymorphism, which is strongly
      associated with serum UA levels in healthy individuals of the general population
      with normal renal function, holds a strong predictive power for CKD progression.
      These findings are compatible with the hypothesis that the link between UA and
      CKD progression is causal in nature.

PMID- 24742480
TI  - Methodologic issues in the measurement of urinary renin.
AB  - BACKGROUND AND OBJECTIVES: Alge et al. recently reported that urinary renin may
      be a prognostic biomarker for AKI after cardiac surgery. However, their urinary
      renin levels far exceeded published plasma renin levels, whereas normally,
      urinary renin is <10% of plasma renin. This result raises questions about the
      specificity of the new Quantikine Renin ELISA Kit used in the work by Alge et
      al., which is claimed to detect total renin (i.e., renin and prorenin).
      Therefore, this study tested this assay. DESIGN, SETTING, PARTICIPANTS, &
      MEASUREMENTS: Plasma and urine from 30 patients with hypertension, diabetes, or
      preeclampsia and 10 healthy pregnant women (randomly selected from sample sets
      obtained earlier to investigate urinary renin-angiotensin system components) were
      used to compare the ELISA with a validated renin immunoradiometric assay and an
      in-house enzyme kinetic assay. Measurements were performed before and after in
      vitro prorenin activation, representing renin and total renin, respectively.
      RESULTS: Total renin measurements by ELISA, immunoradiometric assay, and enzyme
      kinetic assay were highly correlated. However, ELISA results were consistently
      >=10-fold higher. The ELISA standard yielded low to undetectable levels in the
      immunoradiometric assay and enzyme kinetic assay, except after prorenin
      activation, when the results were >=10-fold lower than the ELISA results. In
      plasma, prorenin activation increased ELISA results by 10%-15%. Urine contained
      no detectable prorenin. CONCLUSIONS: The ELISA renin kit standard is prorenin,
      and its immunoreactivity and enzymatic activity after conversion to renin do not
      match the International Reference Preparation of human renin that has been used
      to validate previous immunoradiometric assays and enzyme kinetic assays; in fact,
      they are at least 10-fold lower, and thus, any measurements obtained with this
      ELISA kit yield levels that are at least 10-fold too high. The ELISA antibodies
      detect both renin and prorenin, with a preference for the former. Given these
      inconsistencies, urinary renin levels should be measured by established renin
      assays.

PMID- 24742481
TI  - Serum creatinine changes associated with critical illness and detection of
      persistent renal dysfunction after AKI.
AB  - BACKGROUND AND OBJECTIVES: AKI is a risk factor for development or worsening of
      CKD. However, diagnosis of renal dysfunction by serum creatinine could be
      confounded by loss of muscle mass and creatinine generation after critical
      illness. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: A retrospective, single
      center analysis of serum in patients surviving to hospital discharge with an
      intensive care unit admission of 5 or more days between 2009 and 2011 was
      performed. RESULTS: In total, 700 cases were identified, with a 66% incidence of
      AKI. In 241 patients without AKI, creatinine was significantly lower (P<0.001) at
      hospital discharge than admission (median, 0.61 versus 0.88 mg/dl; median
      decrease, 33%). In 160 patients with known baseline, discharge creatinine was
      significantly lower than baseline in all patients except those patients with
      severe AKI (Kidney Disease Improving Global Outcomes category 3), who had no
      significant difference. In a multivariable regression model, median duration of
      hospitalization was associated with a predicted 30% decrease (95% confidence
      interval, 8% to 45%) in creatinine from baseline in the absence of AKI; after
      allowing for this effect, AKI was associated with a 29% (95% confidence interval,
      10% to 51%) increase in predicted hospital discharge creatinine. Using a similar
      model to exclude the confounding effect of prolonged major illness on creatinine,
      148 of 700 patients (95% confidence interval, 143 to 161) would have eGFR<60
      ml/min per 1.73 m(2) at hospital discharge compared with only 63 of 700 patients
      using eGFR based on unadjusted hospital creatinine (a 135% increase in potential
      CKD diagnoses; P<0.001). CONCLUSION: Critical illness is associated with
      significant falls in serum creatinine that persist to hospital discharge,
      potentially causing inaccurate assessment of renal function at discharge,
      particularly in survivors of AKI. Prospective measurements of GFR and creatinine
      generation are required to confirm the significance of these findings.

PMID- 24742482
TI  - The value of improving value.

PMID- 24742483
TI  - Neuropathic pain after mandibular ramus sagittal split osteotomy.

PMID- 24742484
TI  - Bone tissue engineering by way of allograft revitalization: mechanistic and
      mechanical investigations using a porcine model.
AB  - PURPOSE: "Allograft revitalization" is a process in which cadaveric bone is used
      to generate well-vascularized living bone. We had previously found that porcine
      allograft hemimandibles filled with autologous adipose-derived stem cells (ASCs)
      and recombinant human bone morphogenetic protein-2-soaked absorbable collagen
      sponge (rhBMP-2/ACS) were completely replaced by vascularized bone, provided the
      construct had been incubated within a periosteal envelope. The present study
      sought to deepen our understanding of allograft revitalization by investigating
      the individual contributions of ASCs and rhBMP-2 in the process and the
      mechanical properties of the revitalized allograft. MATERIALS AND METHODS:
      Porcine allograft hemimandible constructs were implanted bilaterally into rib
      periosteal envelopes in 8 pigs. To examine the contributions of ASCs and rhBMP-2,
      the following groups were assessed: group 1, periosteum alone; group 2,
      periosteum+ASCs; group 3, periosteum+rhBMP-2/ACS; and group 4,
      periosteum+ASCs+rhBMP-2/ACS. After 8 weeks, the allograft constructs were
      harvested for micro-computed tomography (CT) and histologic analyses and 3-point
      bending to assess the strength. RESULTS: On harvesting, the constructs receiving
      rhBMP-2/ACS had significantly greater bone shown by micro-CT than those receiving
      periosteum only (51,463 vs. 34,310 mm3; P = .031). The constructs receiving ASCs
      had increased bone compared to group 1 (periosteum only), although not
      significantly (P = .087). The combination of rhBMP-2/ACS with ASCs produced bone
      (50,399 mm3) equivalent to that of the constructs containing rhBMP-2/ACS only.
      The 3-point bending tests showed no differences between the 4 groups and a
      nonimplanted allograft or native mandible (P = .586), suggesting the absence of
      decreased strength of the allograft bone when revitalized. CONCLUSIONS: These
      data have shown that rhBMP-2/ACS significantly stimulates new bone formation by
      way of allograft revitalization and that the revitalized allograft has equivalent
      mechanical strength to native bone.

PMID- 24742485
TI  - Eagle's syndrome associated with lingual nerve paresthesia: a case report.
AB  - Eagle's syndrome is characterized by a variety of symptoms, including throat
      pain, sensation of a foreign body in the pharynx, dysphagia, referred otalgia,
      and neck and throat pain exacerbated by head rotation. Any styloid process longer
      than 25 mm should be considered elongated and will usually be responsible for
      Eagle's syndrome. Surgical resection of the elongated styloid is a routine
      treatment and can be accomplished using a transoral or an extraoral approach. We
      report a patient with a rare giant styloid process that was approximately 81.7
      mm. He complained of a rare symptom: hemitongue paresthesia. After removal of the
      elongated styloid process using the extraoral approach, his symptoms, including
      the hemitongue paresthesia, were alleviated. We concluded that if the styloid
      process displays medium to severe elongation, the extraoral approach will be
      appropriate. 

PMID- 24742486
TI  - Conservative treatment and implant rehabilitation of the mandible in a case of
      craniofacial fibrous dysplasia: a case report.
AB  - We present a case of implant rehabilitation of the mandible in a young patient
      affected by craniofacial fibrous dysplasia. A computed tomography scan showed
      involvement of the left orbital contour and left maxilla, with total involvement
      of the mandible. We performed conservative surgical treatment from 2004 to 2011
      to reconstruct and recontour the orbital and mandible region. Next, we performed
      implant rehabilitation of the mandible. This case emphasizes the importance of
      conservative and nondemolition treatment to obtain excellent functional and
      esthetic results. 

PMID- 24742487
TI  - Determining the location of the body's center of mass for different groups of
      physically active people.
AB  - The purpose of the present study was to compare the location of the body center
      of mass (CoM) determined by using a high accuracy reaction board (RB) and two
      different segment parameter models for motion analysis (Dempster, 1955, DEM and
      de Leva, 1996 adjusted from Zatsiorsky and Seluyanov, ZAT). The body CoM
      (expressed as percentage of the total body height) was determined from several
      subjects including athletes as well as physically active students and sedentary
      people. Some significant differences were found in the location of the body CoM
      between the used segment models and the reaction board method for all male
      subjects (n=58, 57.03+/-0.79%, 56.20+/-0.76% and 57.60+/-0.76% for RB, ZAT and
      DEM, respectively) and separately for male (n=12, RB 57.02+/-0.41%, ZAT 56.74+/
      0.62%, DEM 58.19+/-0.60%) and female (n=12, RB 55.91+/-0.88%, ZAT 57.24+/-0.77%)
      students of physical activity. The ZAT model was a good match with RB for high
      jumpers (56.26+/-0.94% and 56.63+/-0.56%) whereas the DEM model was better for
      gymnasts (57.38+/-0.46% and 57.89+/-0.49%) and throwers (58.19+/-0.69% and
      57.79+/-0.45%). For ice hockey players (IH) and ski jumpers (SJ) both segment
      models, ZAT and DEM, differed significantly from the reaction board results. The
      results of the present study showed that careful attention should be paid while
      selecting the proper model for motion analysis of different type of athletes. 

PMID- 24742488
TI  - Power law, is it a fundamental law of cultural organization?: Comment on
      "Modelling language evolution: Examples and predictions" by Tao Gong, Lan Shuai,
      Menghan Zhang.

PMID- 24742489
TI  - The scope and limits of action semantics: Reply to comments on 'Action semantics:
      A unifying conceptual framework for the selective use of multimodal and modality
      specific object knowledge'.

PMID- 24742491
TI  - A novel challenge model to evaluate the efficacy of hepatitis C virus vaccines in
      mice.
AB  - An effective hepatitis C virus (HCV) vaccine should elicit robust humoral and
      cell mediated immunity (CMI). A small animal challenge model is required to
      assess the efficacy of vaccines which elicit CMI. In this study, HCV proteins
      were expressed in hepatocytes of immunocompetent mice after hydrodynamic
      injection of a plasmid encoding the HCV NS3/4A protein. This vector, constructed
      as the "challenge", was optimized for long term, specific gene expression in
      hepatocytes. To monitor HCV antigen expression in transfected hepatocytes, the
      plasmid also encoded secreted alkaline phosphatase (SEAP), which was detected in
      the mouse serum. The design of this novel challenge plasmid was based on studies
      using luciferase and SEAP as reporter molecules to examine the kinetics of the
      proteins expressed in hepatocytes and secreted into blood. We designed two
      constructs to control SEAP expression. In one construct, SEAP expression was
      controlled by the EMCV IRES, while in the other, a SEAP and luciferase
      polyprotein was cleaved by the FMDV2A proteinase. We found that SEAP expressed
      after FMDV2A self cleavage was more sensitive and showed a higher correlation
      with luciferase expressed in liver. The NS3/4A challenge model using the FMDV2A
      design provided a window period of 50 days to monitor changes in SEAP expression
      after hydrodynamic injection of DNA. In a challenge experiment, mice which
      received an adenovirus-based HCV vaccine showed accelerated clearance of SEAP and
      thus, of NS3/4A positive hepatocytes compared with a mock vaccinated group, that
      coincided with an increased number of CD8(+) lymphocytes in the liver. 

PMID- 24742490
TI  - Safety of influenza vaccination during pregnancy: a review of subsequent maternal
      obstetric events and findings from two recent cohort studies.
AB  - Pregnant women and their infants are vulnerable to severe disease and secondary
      complications from influenza infection. For this reason, annual influenza
      vaccination is recommended for all pregnant women in the United States. Women
      frequently cite concerns about vaccine safety as a barrier to vaccination. This
      review describes the safety of inactivated influenza vaccination during pregnancy
      with a focus on maternal obstetric events, including hypertensive disorders,
      gestational diabetes, and chorioamnionitis. Included in the review are new
      findings from two studies which examined the safety of seasonal inactivated
      influenza vaccination during pregnancy. The first study enrolled 641 pregnant
      women during the 2010-2011 season and prospectively followed them until delivery
      or pregnancy termination. The second study enrolled 1616 pregnant women during
      the 2010-2011 influenza season, and followed the women and their infants for six
      months after delivery. No associations between inactivated influenza vaccination
      and gestational diabetes, gestational hypertension, preeclampsia/eclampsia, or
      chorioamnionitis were observed in either cohort. When considered as a whole,
      these studies should further reassure women and clinicians that influenza
      vaccination during pregnancy is safe for mothers. 

PMID- 24742492
TI  - TBX2 represses CST6 resulting in uncontrolled legumain activity to sustain breast
      cancer proliferation: a novel cancer-selective target pathway with therapeutic
      opportunities.
AB  - TBX2 is an oncogenic transcription factor known to drive breast cancer
      proliferation. We have identified the cysteine protease inhibitor Cystatin 6
      (CST6) as a consistently repressed TBX2 target gene, co-repressed through a
      mechanism involving Early Growth Response 1 (EGR1). Exogenous expression of CST6
      in TBX2-expressing breast cancer cells resulted in significant apoptosis whilst
      non-tumorigenic breast cells remained unaffected. CST6 is an important tumor
      suppressor in multiple tissues, acting as a dual protease inhibitor of both
      papain-like cathepsins and asparaginyl endopeptidases (AEPs) such as Legumain
      (LGMN). Mutation of the CST6 LGMN-inhibitory domain completely abrogated its
      ability to induce apoptosis in TBX2-expressing breast cancer cells, whilst
      mutation of the cathepsin-inhibitory domain or treatment with a pan-cathepsin
      inhibitor had no effect, suggesting that LGMN is the key oncogenic driver enzyme.
      LGMN activity assays confirmed the observed growth inhibitory effects were
      consistent with CST6 inhibition of LGMN. Knockdown of LGMN and the only other
      known AEP enzyme (GPI8) by siRNA confirmed that LGMN was the enzyme responsible
      for maintaining breast cancer proliferation. CST6 did not require secretion or
      glycosylation to elicit its cell killing effects, suggesting an intracellular
      mode of action. Finally, we show that TBX2 and CST6 displayed reciprocal
      expression in a cohort of primary breast cancers with increased TBX2 expression
      associating with increased metastases. We have also noted that tumors with
      altered TBX2/CST6 expression show poor overall survival. This novel TBX2-CST6
      LGMN signaling pathway, therefore, represents an exciting opportunity for the
      development of novel therapies to target TBX2 driven breast cancers. 

PMID- 24742493
TI  - A TGF-beta receptor 1 inhibitor for prevention of proliferative
      vitreoretinopathy.
AB  - This study evaluates the use of the TGF-beta receptor 1 inhibitor LY-364947 (LY)
      to prevent proliferative vitreoretinopathy (PVR). For the in vitro experiments
      Human Tenon's Fibroblasts (HTFs) and retinal pigment epithelial (RPE) cells were
      treated with different concentrations of LY to determine HTF proliferation and
      RPE transdifferentiation. For in vivo testing 30 rabbits underwent a PVR trauma
      model. The animals received different concentrations of intravitreally injected
      LY, with or without vitrectomy. LY treatment reduced HTF proliferation and RPE
      transdifferentiation in vitro. In vivo intravitreal injection of LY prevented PVR
      development significantly. This positive effect was also present when LY
      injection was combined with vitrectomy. Intravitreal injection of LY prevented
      tractional retinal detachment in 14 out of 15 animals. In conclusion, treatment
      with the TGF-beta receptor 1 inhibitor LY reduces HTF proliferation and RPE
      transdifferentiation in vitro and prevents proliferative vitreoretinopathy and
      subsequent tractional retinal detachment in vivo.

PMID- 24742495
TI  - Comparison of the king vision video laryngoscope with the macintosh laryngoscope.
AB  - BACKGROUND: Endotracheal intubation is a common procedure in the emergency
      department, and new devices may improve intubation time, success, or view.
      OBJECTIVE: We compared the King Vision video laryngoscope (KVVL; King Systems,
      Noblesville, IN) to the Macintosh direct laryngoscope (DL) in simulated normal
      and difficult airways. METHODS: Using manikins and clinical-grade cadavers,
      difficult airway scenarios were simulated using head movement restriction or a
      cervical spine collar. Four scenarios were studied using the KVVL and DL: normal
      manikin airway, difficult manikin airway, normal cadaver airway, and difficult
      cadaver airway. Primary outcomes were time to intubation and rate of successful
      intubation. Secondary outcomes were the percent of glottic opening and Cormack
      Lehane grade visualized. RESULTS: Thirty-two paramedics participated in the
      study. In the normal manikin airway scenario, time to intubation was 3.4 s (99%
      confidence interval [CI] 0.1-6.6) faster with the KVVL compared with DL. Time to
      intubation was 11.3 s (99% CI 2.4-20.2) faster with the KVVL in the difficult
      cadaver airway scenario. There was no difference in time to intubation in the
      other 2 scenarios. In the difficult cadaver airway, 10 of 32 participants failed
      to successfully intubate the trachea using DL, whereas all KVVL intubations were
      successful. All scenarios found a lower Cormack-Lehane grade and higher
      percentage of glottic opening with the KVVL compared to DL. CONCLUSION: The KVVL
      was slightly faster than Macintosh DL in two of four studied airway scenarios,
      and had a higher success rate in the difficult cadaver airway scenario. Further
      study is required in the clinical setting.

PMID- 24742494
TI  - Gene expression signatures in tree shrew choroid during lens-induced myopia and
      recovery.
AB  - Gene expression in tree shrew choroid was examined during the development of
      minus-lens induced myopia (LIM, a GO condition), after completion of minus-lens
      compensation (a STAY condition), and early in recovery (REC) from induced myopia
      (a STOP condition). Five groups of tree shrews (n = 7 per group) were used.
      Starting 24 days after normal eye-opening (days of visual experience [DVE]), one
      minus-lens group wore a monocular -5 D lens for 2 days (LIM-2), another minus
      lens group achieved stable lens compensation while wearing a monocular -5 D lens
      for 11 days (LIM-11); a recovery group also wore a -5 D lens for 11 days and then
      received 2 days of recovery starting at 35 DVE (REC-2). Two age-matched normal
      groups were examined at 26 DVE and 37 DVE. Quantitative PCR was used to measure
      the relative differences in mRNA levels in the choroid for 77 candidate genes
      that were selected based on previous studies or because a whole-transcriptome
      analysis suggested their expression would change during myopia development or
      recovery. Small myopic changes were observed in the treated eyes of the LIM-2
      group (-1.0 +/- 0.2 D; mean +/- SEM) indicating eyes were early in the process of
      developing LIM. The LIM-11 group exhibited complete refractive compensation (-5.1
      +/- 0.2 D) that was stable for five days. The REC-2 group recovered by 1.3 +/-
      0.3 D from full refractive compensation. Sixty genes showed significant mRNA
      expression differences during normal development, LIM, or REC conditions. In LIM
      2 choroid (GO), 18 genes were significantly down-regulated in the treated eyes
      relative to the fellow control eyes and 10 genes were significantly up-regulated.
      In LIM-11 choroid (STAY), 10 genes were significantly down-regulated and 12 genes
      were significantly up-regulated. Expression patterns in GO and STAY were similar,
      but not identical. All genes that showed differential expression in GO and STAY
      were regulated in the same direction in both conditions. In REC-2 choroid (STOP),
      4 genes were significantly down-regulated and 18 genes were significantly up
      regulated. Thirteen genes showed bi-directional regulation in GO vs. STOP. The
      pattern of differential gene expression in STOP was very different from that in
      GO or in STAY. Significant regulation was observed in genes involved in signaling
      as well as extracellular matrix turnover. These data support an active role for
      the choroid in the signaling cascade from retina to sclera. Distinctly different
      treated eye vs. control eye mRNA signatures are present in the choroid in the GO,
      STAY, and STOP conditions. The STAY signature, present after full compensation
      has occurred and the GO visual stimulus is no longer present, may participate in
      maintaining an elongated globe. The 13 genes with bi-directional expression
      differences in GO and STOP responded in a sign of defocus-dependent manner. Taken
      together, these data further suggest that a network of choroidal gene expression
      changes generate the signal that alters scleral fibroblast gene expression and
      axial elongation rate.

PMID- 24742496
TI  - Correlates of suicide attempts among self-injurers: a meta-analysis.
AB  - Suicide attempts (SAs) are common among those who engage in non-suicidal self
      injury (NSSI). It is therefore important to determine which suicide risk factors
      are most predictive of SA among those who self-injure. Toward this aim, we
      conducted a systematic review of studies examining predictors of SA history among
      self-injurers. A total of 52 empirical articles provided data comparing self
      injurers with and without SA. From these studies we focused our meta-analysis on
      the 20 variables that were evaluated with respect to SA history in five or more
      different samples. The strongest correlate of SA history was suicidal ideation.
      After suicidal ideation, the strongest predictors of SA history were NSSI
      frequency, number of NSSI methods, and hopelessness. Additional, moderate
      predictors of SA history included Borderline Personality Disorder, impulsivity,
      Post-Traumatic Stress Disorder, the NSSI method of cutting, and depression.
      Demographic characteristics, such as gender, ethnicity, and age, were weakly
      associated with SA history. Notably, some oft-cited risk factors for SA displayed
      small or negligible associations with SA among self-injurers, including histories
      of sexual and physical abuse, anxiety, substance use, and eating disorders.
      Findings have implications for conceptual models of the NSSI-SA relationship and
      the evaluation of suicide risk among self-injuring populations. 

PMID- 24742497
TI  - Low vitamin D as a risk factor for the development of myalgia in patients taking
      high-dose simvastatin: a retrospective review.
AB  - BACKGROUND: Statins are the treatment of choice for dyslipidemia, primarily
      lowering elevated LDL-C levels and reducing the occurrence of major
      cardiovascular events. In June 2011, the Food and Drug Administration issued a
      warning regarding the use of high-dose simvastatin 80 mg and its risk of
      myopathy. OBJECTIVE: The incidence of myalgia, myopathy, and rhabdomyolysis was
      analyzed in a veteran population prescribed simvastatin 80 mg. Risk factors for
      myalgia were examined and compared with the results of recently published
      studies. METHODS: This was a retrospective medical record review of 450 patients
      who were prescribed simvastatin 80 mg at the Veterans Affairs Western New York
      Healthcare System between August 1, 2006, and July 31, 2011. Records were
      examined for evidence of myalgia, myopathy (incipient or definite), and
      rhabdomyolysis. Variables that may have contributed to the development of myalgia
      were also collected and analyzed. RESULTS: Myalgia was reported by 50 patients
      (11.1%), whereas rhabdomyolysis developed in 1 patient (0.22%). No patient fit
      the criteria for myopathy (incipient or definite). Myalgia was statistically more
      likely to occur in younger patients, patients with a history of myalgia, and
      patients with low vitamin D levels. The mean (SD) vitamin D level in patients
      experiencing myalgia was 26.2 (12.9) versus 36.3 (11.8) ng/mL. The 25
      hydroxyvitamin D level in those who reported myalgia was approximately 10 ng/mL
      lower compared with those who tolerated simvastatin 80 mg (P = 0.0003). There was
      no statistically significant association between length of therapy and
      development of myalgia. CONCLUSION: A lower incidence of adverse muscle events
      with high-dose simvastatin 80 mg was found in patients with higher vitamin D
      levels, suggesting that correction of 25-hydroxyvitamin D levels before statin
      therapy initiation may mitigate one risk factor in the development of statin
      related myalgia. Vitamin D insufficiency appears to be a risk factor for the
      development of myalgia.

PMID- 24742498
TI  - Evaluation of the efficacy and tolerability of fixed-dose combination therapy of
      azilsartan and amlodipine besylate in Japanese patients with grade I to II
      essential hypertension.
AB  - BACKGROUND: Guidelines for the management of hypertension recommend using drugs
      with different mechanisms of action in antihypertensive regimens that include
      simple single-pill fixed-dose combination (FDC) products. OBJECTIVE: The
      objective of this study was to compare the efficacy and tolerability of the FDC
      of azilsartan (AZI) and amlodipine besylate (AML) with those of AZI monotherapy
      and AML monotherapy in Japanese patients with grade 1 to 2 essential
      hypertension. METHODS: This was a multicenter, randomized, double-blind, parallel
      group study. After receiving placebo during a 4-week run-in period in a single
      blind manner, patients were randomized to receive 1 of the following 5 treatments
      for 8 weeks: FDC containing AZI 20 mg and AML 5 mg (AZI/AML 20/5 mg), FDC
      containing AZI 20 mg and AML 2.5 mg (AZI/AML 20/2.5 mg), AZI 20 mg, AML 5 mg, or
      AML 2.5 mg once daily in a fasting or fed state. The primary end point was the
      change from baseline (week 0) in the seated trough diastolic blood pressure at
      week 8 (last observation carried forward [LOCF]), and the secondary end point was
      the change from baseline in the seated trough systolic blood pressure at week 8
      (LOCF). Tolerability was assessed based on adverse events, vital signs, and
      physical examination findings. RESULTS: Of the 800 patients who provided informed
      consent, 603 were randomized to receive AZI/AML 20/5 mg (150 patients), AZI/AML
      20/2.5 mg (151 patients), AZI 20 mg (151 patients), AML 5 mg (75 patients), or
      AML 2.5 mg (76 patients). The mean baseline systolic/diastolic blood pressure was
      160.7/100.3 mm Hg. The mean change from baseline in seated blood pressure at week
      8 (LOCF) was -35.3/-22.3 mm Hg in the AZI/AML 20/5 mg group and -31.4/-19.2 mm Hg
      in the AZI/AML 20/2.5 mg group, indicating a reduction significantly greater than
      that in corresponding monotherapy groups (-21.5/-13.9 mm Hg in the AZI 20 mg
      group, -26.4/-15.5 mm Hg in the AML 5 mg group, and -19.3/-11.6 mm Hg in the AML
      2.5 mg group; p < 0.0001 for all contrast tests). No remarkable difference was
      found in the incidences of adverse events, vital signs, and physical examination
      findings among the treatment groups. CONCLUSION: This study found that the FDC of
      AZI/AML 20/5 mg and 20/2.5 mg exhibited greater antihypertensive effects compared
      with each monotherapy. The FDC of AZI/AML had a similar safety profile to that of
      each monotherapy and was tolerable to Japanese patients with grade 1 to 2
      essential hypertension. JAPAN PHARMACEUTICAL INFORMATION CENTER REGISTRATION:
      Japic CTI-111606.

PMID- 24742499
TI  - Rotavirus g12 in Spain: 2004-2006.

PMID- 24742500
TI  - Leap motion gesture control with OsiriX in the operating room to control imaging:
      first experiences during live surgery.

PMID- 24742501
TI  - Glycation: the angiogenic paradox in aging and age-related disorders and
      diseases.
AB  - Angiogenesis is generally a quiescent process which, however, may be modified by
      different physiological and pathological conditions. The "angiogenic paradox" has
      been described in diabetes because this disease impairs the angiogenic response
      in a manner that differs depending on the organs involved and disease evolution.
      Aging is also associated with pro- and antiangiogenic processes. Glycation, the
      post-translational modification of proteins, increases with aging and the
      progression of diabetes. The effect of glycation on angiogenesis depends on the
      type of glycated proteins and cells involved. This complex link could be
      responsible for the "angiogenic paradox" in aging and age-related disorders and
      diseases. Using diabetes as a model, the present work has attempted to review the
      age-related angiogenic paradox, in particular the effects of glycation on
      angiogenesis during aging. 

PMID- 24742502
TI  - Molecular action mechanisms of solar infrared radiation and heat on human skin.
AB  - The generation of ROS underlies all solar infrared-affected therapeutic and
      pathological cutaneous effects. The signaling pathway NF-kB is responsible for
      the induced therapeutic effects, while the AP-1 for the pathological effects. The
      different signaling pathways of infrared-induced ROS and infrared-induced heat
      shock ROS were shown to act independently multiplying the influence on each other
      by increasing the doses of irradiation and/or increasing the temperature. The
      molecular action mechanisms of solar infrared radiation and heat on human skin
      are summarized and discussed in detail in the present paper. The critical doses
      are determined. Protection strategies against infrared-induced skin damage are
      proposed. 

PMID- 24742503
TI  - Isolation and optimization for affinity and biophysical characteristics of anti
      CCL17 antibodies from the VH1-69 germline gene.
AB  - CCL17 is a homeostatic chemokine associated with several human inflammatory
      pathologies. This makes CCL17 a potential point of intervention in inflammatory
      diseases. Using a Fab-pIX phage display system we were able to select antibodies
      that specifically bind to CCL17 and neutralize CCL17-mediated signaling. Many of
      the selected antibodies belong to the VH1-69 germline gene family. The VH1-69
      germline gene is represented at a high frequency in the human antibody repertoire
      and is seen in the early immune response to a variety of pathogens. The heavy
      chain CDR2 of this germline gene is notably hydrophobic and can insert into
      hydrophobic pockets of antigens, providing much of the binding energy for these
      antibodies. Affinity maturation of our primary binders by light chain mutagenesis
      produced antibodies with sub-nanomolar affinities, with affinity improvements up
      to 100-fold. These were screened for non-specific protein-protein interactions as
      a filter for solubility. All of our high affinity antibodies were found to have
      high levels of non-specific protein-protein interactions. We speculated that this
      was due to the hydrophobicity within the germline heavy chain CDR1 and CDR2. To
      ameliorate this problem, we generated a phage display library for one of the
      clones, where the surface-exposed residues within H-CDR1 and H-CDR2 were
      randomized. High stringency panning of this library against human CCL17 resulted
      in further affinity improvement, along with reduction in protein-protein
      interaction in some new variants. In addition, we improved the cross-reactivity
      to cynomolgus CCL17. We demonstrate that affinity maturation through targeted
      libraries in the VH1-69 germline gene can improve both affinity and biophysical
      characteristics of antibodies derived from this gene scaffold. 

PMID- 24742504
TI  - Protease-resistant single-domain antibodies inhibit Campylobacter jejuni
      motility.
AB  - Camelid heavy-chain antibody variable domains (VHHs) are emerging as potential
      antimicrobial reagents. We have engineered a previously isolated VHH (FlagV1M),
      which binds Campylobacter jejuni flagella, for greater thermal and proteolytic
      stability. Mutants of FlagV1M were obtained from an error-prone polymerase chain
      reaction library that was panned in the presence of gastrointestinal (GI)
      proteases. Additional FlagV1M mutants were obtained through disulfide-bond
      engineering. Each approach produced VHHs with enhanced thermal stability and
      protease resistance. When the beneficial mutations from both approaches were
      combined, a hyperstabilized VHH was created with superior stability. The
      hyperstabilized VHH bound C. jejuni flagella with wild-type affinity and was
      capable of potently inhibiting C. jejuni motility in assays performed after
      sequential digestion with three major GI proteases, demonstrating the remarkable
      stability imparted to the VHH by combining our engineering approaches. 

PMID- 24742505
TI  - [Guideline of cochlear implant (2013)].

PMID- 24742506
TI  - [Intensive reading of the guideline of cochlear implant(2013)].

PMID- 24742507
TI  - [Clinical effect of clarithromycin therapy in patients with chronic
      rhinosinusitis].
AB  - OBJECTIVE: To evaluate the efficacy of clarithromycin (CAM) treatment in adult
      Chinese patients suffering from chronic rhinosinusitis with nasal polyps (CRSwNP)
      or without nasal polyps (CRSsNP). METHODS: A prospective, open and self
      controlled clinical trial on patients with CRS was conducted. Fifty patients met
      inclusion criteria. Of 50 patients, there were 33 patients with CRSsNP and 17
      patients with CRSwNP. CAM was administered at 250 mg/d and the duration of
      administration was 12 weeks. Outcome measures included assessments of visual
      analogue scale (VAS), the sino-nasal outcome test-20(SNOT-20), the medical
      outcomes study short-form 36 items(SF-36), Lund-Kennedy endoscopy score, and Lund
      Mackay computed tomography score. Before starting the treatment, 2 months after
      treatment and at the end of treatment, each patient had to complete all the
      measures except Lund-Mackay computed tomography score, which was only conducted
      before and after treatment. In order to evaluate the safety of CAM, liver
      function and renal function in all patients were detected before and after
      treatment. SPSS 16.0 software was used to analyze the data. RESULTS: Forty-five
      patients completed 3 months follow-up and 5 patients withdrew due to different
      reasons. The results were as follows: (1) Thirty-three patients with CRSsNP's VAS
      scores of four time point were 5.81 +/- 1.69, 3.76 +/- 1.94, 2.98 +/- 1.95, 2.06
      +/- 2.13, respectively, there were statistically significant improvements in turn
      (t values were 5.910, 8.090, 8.932, all P < 0.05). Endoscopy score of four time
      point were 6.28 +/- 1.28, 5.00 +/- 1.67, 4.12 +/- 1.76, 3.12 +/- 2.19,
      respectively, there were statistically significant improvements in turn compared
      with before treatment (t values were 6.662, 9.161, 9.936, all P < 0.05). The CT
      scores before and after treatment were 10.33 +/- 4.65 and 4.67 +/- 4.59,
      respectively (t = 7.226, P = 0.000) . (2) Seventeen patients with CRSwNP's VAS
      scores of four time point were 6.07 +/- 2.02, 4.87 +/- 2.61, 4.06 +/- 2.85, 4.08
      +/- 2.80, respectively, there were statistically significant improvements after 2
      or 3 months (t values were 3.285, 3.468, both P < 0.05) except after one month (t
      = 1.846, P > 0.05). Endoscopy score of four time point were 10.65 +/- 1.77, 9.35
      +/- 1.93, 8.65 +/- 2.76, 8.47 +/- 2.76, respectively, there were statistically
      significant improvements in turn(t values were 4.068, 4.863, 5.156, all P <
      0.05). The CT scores before and after treatment were 13.82 +/- 4.94 and 11.41 +/-
      5.12, respectively (t = 3.975, P = 0.001). (3) During the period of CAM
      treatment, 1 patient reported a tolerable headache and weakness and 1 patient had
      abdominal pain after two months treatment, all the symptoms disappeared while
      they were asked to stop the drug. Liver function and renal function were detected
      in 40 patients, the differences before and after treatment were not significant
      statistically. CONCLUSIONS: Long-term, low-dose CAM treatment is effective in the
      treatment of CRSsNP and CRSwNP in Chinese patients. Meanwhile, the efficacy of
      CAM is more significant in polyp-free group compared with polyp group. Low does
      CAM therapy is safe, and the liver function and renal function does not worsen
      after 3 months treatment.

PMID- 24742508
TI  - [Treatment of allergic rhinitis with normal saline nasal irrigation at different
      temperature].
AB  - OBJECTIVE: To investigate the influence of normal saline nasal irrigation with
      different temperature on allergic rhinitis (AR) and to confirm the appropriate
      temperature of nasal irrigation. METHODS: Sixty patients with AR were randomly
      divided into 3 groups (according to random number table) and received 15  degrees
      C, 25  degrees C or 40  degrees C normal saline nasal irrigation respectively,
      and 20 healthy controls received no treatment. Visual analogue scale ( VAS) was
      used to assess the symptoms among the control group and the various intervention
      groups and the enzyme linked immunosorbent assay (ELISA) was applied to detect
      the contents of histamine, leukotriene C4 (LTC4), house dust mite D1 specific IGE
      (sIGE) and eosinophil cationic protein (ECP) among the control group and the
      various intervention groups. GraphPad Prism 5 software was used to analyze the
      data. RESULTS: There was no statistical difference between 15  degrees C normal
      saline nasal irrigation group and 25  degrees C normal saline nasal irrigation
      group. Pre-intervention and post intervention whether is VAS scores of
      rhinorrhea, sneezing, nasal obstruction and nasal pruritis or in contents of
      histamine, LTC4, sIgE and ECP showed no difference (all P > 0.05). However, the
      symptoms of (sneezing VAS score: 3.765 +/- 0.291; nasal obstruction VAS score:
      3.529 +/- 0.365). The difference was significant (t = 4.678, P < 0.001; t =
      3.901, P < 0.01). The contents of histamine [ (21.78 +/- 0.62) ng/ml] and LTC4
      (17.43 +/- 0.67 ng/ml) were also decreased after intervention of 40  degrees C
      normal saline nasal irrigation [ histamine content: (18.82 +/- 0.52) ng/ml; LTC4
      content: (13.14 +/- 0.59) ng/ml ]. The difference was significant (t = 3.632, P <
      0.01; t = 4.79, P < 0.001). Nonetheless, there were no statistical differences in
      VAS scores of rhinorrhea (t = 2.02, P = 0.051) and nasal pruritis (t = 1.984, P
      =0.056) and in contents of sIgE (t = 1.891, P = 0.066) and ECP (t = 2.021, P =
      0.05). There were statistical differences between the 40  degrees C group and the
      25  degrees C group normal saline nasal irrigation group in symptoms of sneezing
      (t = 2.060, P = 0.048) and nasal obstruction (t = 2.1053, P = 0.048). and
      inflammatory factors of histamine (t = 2.078, P = 0.045) and LTC4 (t = 2.149, P =
      0.038). In symptoms of rhinorrhea and nasal pruritis and local production of sIgE
      and ECP, there was no statistical difference (all P > 0.05). CONCLUSION: 40 
      degrees C normal saline nasal irrigation can improve the symptoms of sneezing and
      nasal obstruction and can alleviate the local levels of inflammatory factors like
      histamine and LTC4 in AR patients, and is the appropriate irrigation temperature.

PMID- 24742509
TI  - [Clinical characteristics of primary ciliary dyskinesia].
AB  - OBJECTIVE: To analyze the clinical characteristics of primary ciliary
      dyskinesia(PCD) so as to improve the diagnostic level of this rarely seen
      disease. METHODS: Ten patients with PCD were retrospectively reviewed, the
      medical history, symptoms, signs, lung CT or chest X-ray, rhino-sinus CT scan,
      nasal nitric oxide (NO) levels, nasal ciliary ultrastructure, DNAH5 and DNAH11
      genetic mutation, as well as treatment outcome were analyzed. RESULTS: All 10
      patients had recurrent chronic sinusitis, otitis media, bronchitis/bronchiectasis
      since childhood. Nine cases with translocation of heart and big vessels were
      diagnosed as Kartagener syndrome. One woman was suffering from barrenness and one
      man sterility after marriage for long time without birth control. Nasal NO levels
      were significantly lower in 2 patients with PCD but it was almost normal in one
      patient. Ciliary ultrastructure investigated by transmission electron microscope
      were almost normal in 4 cases without missing of inner or outer dynein arms. Two
      cases taking exome capture sequencing showed that mutations happened in DNAH5 and
      DNAH11. Five subjects underwenting sanger sequencing on 6 common exon fragments
      of DNAH5 and DNAH11 did not show any abnormality. Ten cases took medication
      therapy, while 5 patients once underwent functional endoscope sinus surgery. All
      of the 10 patients had improvement of their symptoms and signs after treatment.
      CONCLUSIONS: The PCD is so rare in clinic that it is easily misdiagnosed.
      Clinical characteristics, nasal NO levels, ciliary ultrastructure and genetic
      testing are significant for clinical diagnosis.

PMID- 24742510
TI  - [Analysis of intracranial infection factors after transnasal endoscopic repair of
      cerebrospinal fluid rhinorrhea].
AB  - OBJECTIVE: To analyze the factors of intracranial infection after transnasal
      endoscopic repair of cerebrospinal fluid rhinorrhea. METHODS: One hundred and
      seventy-three patients who accepted transnasal endoscopic repair of cerebrospinal
      fluid rhinorrhea were retrospectively analyzed. The intracranial infection
      factors was analyzed by Logistic regression analysis with SPSS 17.0 software.
      RESULTS: Postoperative infection was found in 17 cases among 173 patients, the
      infection rate was 9.83%. The unsuccessful transnasal endoscopic repair of
      cerebrospinal fluid rhinorrhea (chi(2) = 6.89, P = 0.001) , the defective
      diameter of skull base (chi(2) = 9.98, P = 0.001) and medical history of
      intracranial infection (chi(2) = 11.08, P = 0.001) were infection factors after
      transnasal endoscopic repair of cerebrospinal fluid rhinorrhea (all P < 0.05),
      while sex, age, the site of defection, the aetiological agent, longer application
      of antibiotics before or after operation and the use of artificial material had
      no obvious effect (all P > 0.05). CONCLUSION: Intracranial infection after
      transnasal endoscopic repair of cerebrospinal fluid rhinorrhea is affected by
      many factors, such as the unsuccessful transnasal endoscopic repair of
      cerebrospinal fluid rhinorrhea, the defective diameter of skull base and medical
      history of intracranial infection.

PMID- 24742511
TI  - [Pharyngeal ulcer in patients with acquired immune deficiency syndrome].
AB  - OBJECTIVE: To understand the high incidence of pharyngeal ulcer in patients with
      acquired immune deficiency syndrome (AIDS). By analyzing the clinical features in
      AIDS patients with pharyngeal ulcer, this study provided reference for
      clinicians. METHODS: Twenty AIDS patients with pharyngeal ulcer were
      retrospectively analysed to explore its clinical features and mechanism, and to
      explore the feasible therapeutic methods. RESULTS: The patients generally had
      severe sore throat and dysphagia for 7 days to 8 months, resulting in significant
      weight loss. Common therapeutical method does not work. The ulcers developed
      mainly at vestibule of pharynx (10 cases), tonsil (3 cases), epiglottis (3 cases)
      and pyriform sinus (2 cases). Ulcer types included major aphthous ulcer (MaAU, 14
      cases), fungal ulcer (2 cases), herpes zoster (1 case), ulcer secondary to drug
      eruption(1 case ), and lymphoma(2 cases). The disease course was long with CD4(+)
      T lymphocytes decreased significantly. Treatment was given with highly active
      antiretroviral therapy (HARRT), regulation of immune function, analgesic, anti
      inflammatory and anti fungal. Treatment lasted from 2 weeks to 3 months, ulcer
      healed in 13 cases; 1 patient lost to follow-up, 6 patients dead. CONCLUSIONS:
      The manifestation of pharyngeal ulcer in AIDS patients has its particularity. It
      is often associated with a variety of opportunistic infection and tumors. Local
      treatment is preferred. HAART therapy and systemic comprehensive treatment play
      more important and effective role. Pharyngeal ulcer persists for a long time,
      complicated with fever, diarrhea and other symptoms. The history of blood
      transfusion, injection drug use or unsafe sexual behavior may predict HIV
      infection.

PMID- 24742512
TI  - [Application of enhanced CT in the differential diagnosis of peritonsillar
      abscess and intratonsillar abscess].
AB  - OBJECTIVE: To explore the application of enhanced CT in the differential
      diagnosis and treatment of peritonsillar abscess (PTA) and intratonsillar abscess
      (ITA). METHODS: Thirty-eight in-patients with clinically suspected PTA from June
      2011 to June 2013 were included in this study. All these patients underwent
      enhanced CT scan for the throat region. According to CT results, the location of
      abscess was determined, and the thickness of the posterior wall of abscess as
      well as its distance with the internal carotid artery was calculated.Incision and
      drainage were then guided with this information. RESULTS: Twenty-six of the 38
      patients (68.4%) met the diagnosis of PTA, demonstrating a hypodense collection
      with rim enhancement in the peritonsillar space, including 4 cases with
      multilocular abscess. Ten cases (26.3%) should actually be diagnosed as ITA, with
      a abscess collection located in the palatine tonsil tissue. Two cases(5.3%) were
      diagnosed as peritonsillar cellulitis (PTC), showing diffuse isodense lesion
      around the peritonsillar space. The 26 cases of PTA and 10 cases of ITA patients
      were all cured using incision and drainage under the precise guidance of CT,
      while the 2 cases of PTC only treated with medicine. The mean distance between
      the posterior wall of abscess and the carotid artery (X(-) +/- s) were (0.76 +/-
      0.34) cm and (0.90 +/- 0.37) cm for the two entities respectively, with no
      significant difference (P > 0.05). CONCLUSIONS: Enhanced CT scan can clearly
      demonstrate the characters of PTA and ITA, and make identification. Moreover, it
      is helpful for the determination of therapy, improving the success rate of
      drainage and reducing the potential risk of large artery injury.

PMID- 24742513
TI  - [Angiosarcoma of the head and face: a retrospective study of 15 patients].
AB  - OBJECTIVE: To investigate the clinical and pathological characteristics of
      angiosarcoma of the head and face. METHODS: The data of 15 patients with
      angiosarcoma of the head and face underwent treatment between January 1993 and
      January 2003 were reviewed. Of 15 cases 10 were men and 5 women; 11 tumors in
      scalp and 4 in face; 6 cases of stage I, 3 cases of stage II, 1 case of stage III
      and 5 cases of stage IV. Clinical symptoms included a focal mass or bruiselike
      patches. Surgery alone in 5 cases, chemotherapy alone in 3 cases, comprehensive
      treatment in 5 cases, no treatment in 2 cases. Immunohistochemical staining with
      CD31, CD34 and FVIIIRag was performed in 8 cases. RESULTS: Follow-up time was 3
      240 months with a median of 28 months. One patient of stage I by surgery alone
      and 2 patients of stage I with comprehensive treatment survived for 121, 209 and
      240 months respectively and no recurrence. One patient of stage I with
      comprehensive treatment was survival for 127 months with tumor burden. Eleven
      cases died in 3-78 months after diagnosis, the median follow-up time was 20
      months. Three year and five year survival rates were 46.7% and 33.3%,
      respectively. Immunohistochemical staining showed CD31- and CD34-positive for 8
      cases and FVIIIRag-positive for 6 cases. CONCLUSIONS: Angiosarcoma of the head
      and face is a high-risk sarcoma. It is rare and easily misdiagnosed but can be
      diagnosed properly based on pathological feature. Comprehensive treatment
      including surgery, radiotherapy and chemotherapy can improve survival rate for
      the patients with early stage angiosarcoma.

PMID- 24742514
TI  - [Application of narrow band imaging endoscopy in early diagnosis of
      nasopharyngeal carcinoma].
AB  - OBJECTIVE: To investigate the use of NBI (narrow band imaging) in early the
      diagnosis of nasopharyngeal carcinoma. METHODS: A total of 55 cases with
      nasopharyngeal lesions (including 9 cases of nasopharyngeal carcinoma after
      treatment) were examined and diagnosed by white and NBI endoscopy between October
      2011 and March 2012, and their diagnosis efficacies were evaluated based on
      pathological diagnosis as a gold standard. Chi-square test was used to analyze
      data. RESULTS: Of 55 cases, 12 cases were pathologically diagnosed as chronic
      mucosa inflammation and 43 as nasopharyngeal carcinoma including 6 recurrent
      cases, of 43 cases, 40(93.0%) were diagnosed by NBI endoscopy and 18 (41.9%) by
      white endoscopy. Of 12 cases with early nasopharyngeal carcinoma (5 for stage I
      and 7 for stage II) , 5(100.0%) for stage I, and 6(85.7%) for stage II were
      diagnosed by NBI endoscopy but only 1(14.3%) for stage II by white endoscopy,
      with a statistically significant difference (chi(2) = 10.000, P = 0.008;chi(2) =
      7.143, P = 0.029). CONCLUSION: NBI endoscopy can be used in early diagnosis of
      nasopharyngeal carcinoma and check after treatment.

PMID- 24742515
TI  - [Effects on survival of shRNA mediated APE/Ref1 gene silencing in rat spiral
      ganglion cells in oxidative stress].
AB  - OBJECTIVE: To investigate the effects of reducing APE/Ref1 expression in the
      cultures of rat spiral ganglion cells with oxidative damage induced by H(2)O(2).
      METHODS: Primary cultured rat spiral ganglion cells were infected with small
      interfering RNA to APE/Ref1 (Ape1siRNA) for 72 h, followed by treating with
      H(2)O(2) (0, 10, 25, 50, 100 and 300 umol/L) for 1 h , and then cultured in
      normal medium for 24 h. Western blot were used to detect the level of APE/Ref1
      protein and phosphorylation of histone protein H2AX in the infected cells. The
      caspase3 activation was tested by spectrophotometric method . The cell viability
      was determined by MTT and the apoptosis of spiral ganglion cells was determined
      by terminal-deoxynucleotidyl transferase mediated nick and labeling (TUNEL).
      RESULTS: Western blot showed that infection with Ape1siRNA resulted in APE/Ref1
      reduced expression in the spiral ganglion cells. Exposing spiral ganglion
      cultures with reduced expression of APE/Ref1 to H(2)O(2) (50, 100, 300 umol/L)
      for 1 h resulted in increasing in the phosphorylation of histone protein H2AX.
      The reduction in APE/Ref1 significantly reduced cell viability in cultures 24 h
      after 1 h expression to 50-300 umol/L H(2)O(2). The apoptosis of cells and
      caspase 3 activity was detected significantly improved. CONCLUSIONS: The induced
      of APE/Ref1 results in significantly decrease in spiral ganglion cells viability
      in oxidative stress. The repairing function of APE/Ref1 is necessary for optimal
      levels of neuronal rat spiral ganglion cells survival.

PMID- 24742516
TI  - [Growth inhibitory effect of microRNA-519b-3p on larynx squamous Hep-2 cells].
AB  - OBJECTIVE: To investigate the effects of microRNA-519b-3p (miR-519b-3p) on
      laryngeal carcinoma Hep-2 cell growth, and to analyze the underlying molecular
      mechanisms. METHODS: The effects of miR-519b-3p on the growth and cell cycle of
      Hep-2 cells transfected with miR-519b-3p mimic were tested by MTT assay and flow
      cytometry, respectively. The mRNA and protein expressions of the related genes
      were tested by reverse transcription polymerase chain reaction (RT-PCR) and
      Western blot, respectively. The expressions of miR-519b-3p were tested by real
      time RT-PCR in 48 pairs of laryngeal carcinoma and adjacent tissue samples.
      RESULTS: The expression of miR-519b-3p in laryngeal carcinoma tissues was
      significant lower than that in adjacent non-cancerous tissues (S(DeltaCt) =
      2.989, t = 2.693, P < 0.01) . Increasing the level of miR-519b-3p inhibited
      significantly Hep-2 cell proliferation, arrested the cell cycle in the G2/M phase
      (10.29% +/- 4.63%, t = 4.395, P < 0.05) , and decreased significantly the
      percentage of cells in the S phase (7.56% +/- 2.05%, t = 3.555, P < 0.05) , with
      the increase in the expression of cyclin dependent kinase (CDK) 1 and the
      decrease in the expressions of CDK 2 and Cyclin A. RT-PCR and Western blot showed
      that miR-519b-3p down-regulated the protein but not mRNA expressions of HuR and
      cyclooxygenase-2(COX-2) genes. CONCLUSIONS: The expression of MiR-519b-3p as
      carcinoma suppressor gene is low in laryngeal carcinoma. The cell cycle of Hep-2
      cells was arrested in the G2/M phase by MiR-519b-3p.

PMID- 24742517
TI  - [A case report of congenital fissure of epiglottis].

PMID- 24742518
TI  - [Meta-analysis of the clinical significance of thyroidectomy combined with
      central neck dissection in differentiated thyroid carcinoma at the first
      treatment].
AB  - OBJECTIVE: To compare the differences in recurrence rates and surgical
      complications between thyroidectomy alone and thyroidectomy combined with central
      neck dissection as initial treatments to differentiated thyroid cancer and
      evaluate the clinic significance of central neck dissection for these patients.
      METHODS: The literatures published in 1998-2013 were searched in Wanfang
      database, Chongqing VIP database, Chinese Biomedical Literature Database, China
      National Knowledge Infrastructure, Pubmed, Medline and Beijing Kangjian foreign
      medical journal full text service. According to the inclusion and deletion
      criteria, 30 articles were included. Of them 26 articles involved in
      complications, hypocalcemia and recurrent laryngeal nerve palsy as two major
      complications were involved in 26 articles and 24 articles respectively, and 26
      articles involved in recurrence rate. RevMan5.0 software package was used to
      perform meta-analysis. RESULTS: Total complication rate in experimental group
      (plus central neck dissection) was 13.08% higher than that in control group
      (thyroidectomy only), the odds ratio (OR) [95% confidence interval (95%CI)] was
      2.32[2.02, 2.67], Z value was 11.80, P < 0.01. Hypocalcemia in the experimental
      group was 11.80% higher than that in control group, OR value [95%CI] was
      2.58[2.21, 3.02], Z was 11.98, P < 0.01. The rates of recurrent laryngeal nerve
      paralysis were low in both experimental group (5.26%) and control group(3.95%),
      and OR value [95%CI] was 1.22 [0.94, 1.58], Z was 1.48, P = 0.14. Recurrence rate
      in experimental group was 2.23% lower than that in control group, OR value
      [95%CI] was 0.78 [0.63,0.97], Z was 2.35, P = 0.03. CONCLUSION: Central
      compartment dissection as initial treatment to differentiated thyroid cancer may
      reduce the risk of recurrence, but increases the incidence of total complications
      and hypocalcemia, and has no significant effect on the rate of the recurrent
      laryngeal nerve paralysis.

PMID- 24742519
TI  - [Use of nasal endoscopy to take out fractured tracheostomy tubes in the tracheo
      bronchial tree:a case report].

PMID- 24742520
TI  - [Observation on the effect of cochlear implant in a case with Behcet disease with
      profound hearing loss].

PMID- 24742521
TI  - [Localized laryngeal amyloidosis recurrence on contralateral ventricular fold
      after 6 years].

PMID- 24742522
TI  - [A case of pharyngeal huge chordoma causing difficulty in breathing].

PMID- 24742523
TI  - [Intranasal combination therapy of glucocorticoids and antihistamines in allergic
      rhinitis].

PMID- 24742524
TI  - [Brief introduction to the application of biomedical materials in
      otolaryngology].

PMID- 24742525
TI  - The tricyclic antidepressant desipramine inhibited the neurotoxic, kainate
      induced [Ca(2+)]i increases in CA1 pyramidal cells in acute hippocampal slices.
AB  - Kainate (KA), used for modelling neurodegenerative diseases, evokes
      excitotoxicity. However, the precise mechanism of KA-evoked [Ca(2+)]i increase is
      unexplored, especially in acute brain slice preparations. We used [Ca(2+)]i
      imaging and patch clamp electrophysiology to decipher the mechanism of KA-evoked
      [Ca(2+)]i rise and its inhibition by the tricyclic antidepressant desipramine
      (DMI) in CA1 pyramidal cells in rat hippocampal slices and in cultured
      hippocampal cells. The effect of KA was dose-dependent and relied totally on
      extracellular Ca(2+). The lack of effect of dl-2-amino-5-phosphonopentanoic acid
      (AP-5) and abolishment of the response by 6-cyano-7-nitroquinoxaline-2,3-dione
      (CNQX) suggested the involvement of non-N-methyl-d-aspartate receptors (non
      NMDARs). The predominant role of the Ca(2+)-impermeable alpha-amino-3-hydroxy-5
      methyl-4-isoxazolepropionate receptors (AMPARs) in the initiation of the Ca(2+)
      response was supported by the inhibitory effect of the selective AMPAR antagonist
      GYKI 53655 and the ineffectiveness of 1-naphthyl acetylspermine (NASPM), an
      inhibitor of the Ca(2+)-permeable AMPARs. The voltage-gated Ca(2+) channels
      (VGCC), blocked by omega-Conotoxin MVIIC+nifedipine+NiCl2, contributed to the
      [Ca(2+)]i rise. VGCCs were also involved, similarly to AMPAR current, in the KA
      evoked depolarisation. Inhibition of voltage-gated Na(+) channels (VGSCs;
      tetrodotoxin, TTX) did not affect the depolarisation of pyramidal cells but
      blocked the depolarisation-evoked action potential bursts and reduced the Ca(2+)
      response. The tricyclic antidepressant DMI inhibited the KA-evoked [Ca(2+)]i rise
      in a dose-dependent manner. It directly attenuated the AMPA-/KAR current, but its
      more potent inhibition on the Ca(2+) response supports additional effect on
      VGCCs, VGSCs and Na(+)/Ca(2+) exchangers. The multitarget action on decisive
      players of excitotoxicity holds out more promise in clinical therapy of
      neurodegenerative diseases. 

PMID- 24742526
TI  - Modulation of the extinction of fear learning.
AB  - We review recent work on extinction learning with emphasis on its modulation.
      Extinction is the learned inhibition of responding to previously acquired tasks.
      Like other forms of learning, it can be modulated by a variety of
      neurotransmitter systems and behavioral procedures. This bears on its use in the
      treatment of fear memories, particularly in posttraumatic stress disorder (PTSD),
      for which it is the treatment of choice, often under the name of exposure
      therapy. There have not been many laboratories interested in the modulation of
      extinction, but the available data, although not very abundant, are quite
      conclusive. Most studies on the nature of extinction and on its modulation have
      been carried out on fear motivated behaviors, possibly because of their
      applicability to the therapy of PTSD. A role for d-serine and the glycine site of
      NMDA receptors has been ascertained in two forms of extinction in the
      ventromedial prefrontal cortex, basolateral amygdala and dorsal hippocampus. The
      serine analog, d-cycloserine, has received clinical trials as an enhancer of
      extinction. The brain histaminergic system acting via H2 receptors, and the
      endocannabinoid system using CB1 receptors in the ventromedial prefrontal cortex,
      hippocampus and basolateral amygdala enhance extinction. Dopaminergic D1 and beta
      noradrenergic receptors also modulate extinction by actions on these three
      structures. Isolated findings suggest roles for on serotonin-1A, dopaminergic-D2
      and a- and beta-noradrenergic receptors in extinction modulation. Importantly,
      behavioral tagging and capture mechanisms in the hippocampus have been shown to
      play a major modulatory role in extinction. In addition, extinction of at least
      one aversive task (inhibitory avoidance) can be made state dependent on
      peripheral epinephrine. 

PMID- 24742527
TI  - Brain network function during shifts in learning strategies in portal
      hypertension animals.
AB  - Patients with minimal hepatic encephalopathy exhibit early impairments in their
      ability to shift attentional set. We employed a task-switching protocol to
      evaluate brain network changes. Strategy switching requires the modification of
      both the relevant stimulus dimension and the required memory system. Rats were
      trained in an allocentric (A) and a cue-guided (C) task using a four-arm maze. To
      examine priming, we changed the order in which the tasks were presented. Five
      groups of animals were used: a SHAM (sham-operated) A-C group (n=10), a SHAM C-A
      group (n=8), a PH (portal hypertension) A-C group (n=8), PH C-A group (n=8), and
      a naive group (n=10). The triple portal vein ligation method was used to create
      an animal model of the early evolutive phase of PH. The animals were tested in
      the four-arm radial water maze in a single 10-trial session each day for six days
      (three days for the allocentric task and three days for the cue-guided task). The
      metabolic activities of the brains were studied with cytochrome oxidase
      histochemistry, and brain network changes were assessed with principal component
      analysis. The behavioural results revealed significant increases in the numbers
      of correct choices across training days in all groups studied, and facilitation
      of the acquisition of the second task was present in the C-A groups. Moreover,
      different brain network activities were found; in the experimental groups, the
      performance of A-C switch involved the prefrontal cortex, and the key structures
      involved in the C-A switch in the other groups were the dentate gyrus of the
      dorsal hippocampus and the basolateral and central amygdala. These networks have
      a common nucleus of structures (i.e., the parietal cortex and the dorsal and
      ventral striatum), whereas other structures were specifically involved in each
      type of strategy, suggesting that these regions are part of both circuits and may
      interact with one another during learning. 

PMID- 24742528
TI  - Branding water.
AB  - Branding is a key strategy widely used in commercial marketing to make products
      more attractive to consumers. With the exception of bottled water, branding has
      largely not been adopted in the water context although public acceptance is
      critical to the implementation of water augmentation projects. Based on responses
      from 6247 study participants collected between 2009 and 2012, this study shows
      that (1) different kinds of water - specifically recycled water, desalinated
      water, tap water and rainwater from personal rainwater tanks - are each perceived
      very differently by the public, (2) external events out of the control of water
      managers, such as serious droughts or floods, had a minimal effect on people's
      perceptions of water, (3) perceptions of water were stable over time, and (4)
      certain water attributes are anticipated to be more effective to use in public
      communication campaigns aiming at increasing public acceptance for drinking
      purposes. The results from this study can be used by a diverse range of water
      stakeholders to increase public acceptance and adoption of water from alternative
      sources. 

PMID- 24742529
TI  - Modeling length-tension properties of RCPm muscles during voluntary retraction of
      the head.
AB  - Head retraction exercises are one of several commonly used clinical tools that
      are used to assess and treat patients with head and neck pain and to aid in
      restoration of a normal neutral head posture. Retraction of the head results in
      flexion of the occipitoatlantal (OA) joint and stretching of rectus capitis
      posterior minor (RCPm) muscles. The role that retraction of the head might have
      in treating head and neck pain patients is currently unknown. RCPm muscles arise
      from the posterior tubercle of the posterior arch of C1 and insert into the
      occipital bone inferior to the inferior nuchal line and lateral to the midline.
      RCPm muscles are the only muscles that attach to the posterior arch of C1. The
      functional role of RCPm muscles has not been clearly defined. The goal of this
      project was to develop a three-dimensional, computer-based biomechanical model of
      the posterior aspect of the OA joint. This model should help clarify why
      voluntary head retraction exercises seem to contribute to the resolution of head
      and neck pain and restoration of a normal head posture in some patients. The
      model documents that length-tension properties of RCPm muscles are significantly
      affected by variations in the physical properties of the musculotendonous unit.
      The model suggests that variations in the cross sectional area of RCPm muscles
      due to pathologies that weaken the muscle, such as muscle atrophy, may reduce the
      ability of these muscles to generate levels of force that are necessary for the
      performance of normal, daily activities. The model suggests that the main benefit
      of the initial phase of head retraction exercises may be to strengthen RCPm
      muscles through eccentric contractions, and that the main benefit of the final
      phase of retraction may be to stretch the muscles as the final position is held.

PMID- 24742530
TI  - Inhibition: synapses, neurons and circuits.

PMID- 24742532
TI  - Bangladeshi parental ethnotheories in the United Kingdom: Towards cultural
      collaborations in clinical practice.
AB  - Parental meaning systems (ethnotheories) constitute a very important part of the
      context in which children live and develop. Parental ethnotheories are in turn
      shaped by implicit cultural ideals that organize parental beliefs and actions and
      frame child-rearing practices. The article presents a qualitative research into
      Bangladeshi parental ethnotheories in the United Kingdom, which illustrates both
      the rich cultural meanings that orientate parental action and also demonstrates
      how parents generate new meanings following migration and culture change.
      Professional understandings about children's developmental needs, of child
      rearing and parenting, are not culture free and an examination of the cultural
      frames of professional theories is important as parenting is often taught as a
      universal technique that takes little account of the cultural context and of what
      parents think. An engagement with other cultural theories about child development
      can enhance critical reflexivity in clinical practice by provoking reflection on
      the cultural constructions of professional theories. Creating a context for the
      expression of parental ethnotheories is necessary for developing cross-cultural
      collaborations in clinical practice as it empowers families and redresses the
      power relationship between the therapist and the parent. 

PMID- 24742531
TI  - Roles of neutrophil gelatinase-associated lipocalin (NGAL) in human cancer.
AB  - Cancer remains one of the major cause of death in the Western world. Although, it
      has been demonstrated that new therapies can improve the outcome of cancer
      patients, still many patients relapse after treatment. Therefore, there is a need
      to identify novel factors involved in cancer development and/or progression.
      Recently, neutrophil gelatinase-associated lipocalin (NGAL) has been suggested as
      a key player in different cancer types. Its oncogenic effect may be related to
      the complex NGAL/MMP-9. In the present study, NGAL was analyzed at both
      transcript and protein levels in different cancer types by analysing 38 public
      available microarray datasets and the Human Protein Atlas tool. NGAL transcripts
      were significantly higher in the majority of solid tumors compared to the
      relative normal tissues for every dataset analyzed. Furthermore, concordance of
      NGAL at both mRNA and protein levels was observed for 6 cancer types including
      bladder, colorectal, liver, lung, ovarian, and pancreatic. All metastatic tumors
      showed a decrease of NGAL expression when compared to matched primary lesions.
      According to these results, NGAL is a candidate marker for tumor growth in a
      fraction of solid tumors. Further investigations are required to elucidate the
      function of NGAL in tumor development and metastatic processes. 

PMID- 24742534
TI  - Feasibility of corona discharge ion mobility spectrometry for direct analysis of
      samples extracted by dispersive liquid-liquid microextraction.
AB  - The capability of corona discharge ionization ion mobility spectrometry (CD-IMS)
      for direct analysis of the samples extracted by dispersive liquid-liquid
      microextraction (DLLME) was investigated and evaluated, for the first time. To
      that end, an appropriate new injection port was designed and constructed,
      resulting in possibility of direct injection of the known sample volume, without
      tedious sample preparation steps (e.g. derivatization, solvent evaporation, and
      re-solving in another solvent...). Malathion as a test compound was extracted
      from different matrices by a rapid and convenient DLLME method. The positive ion
      mobility spectra of the extracted malathion were obtained after direct injection
      of carbon tetrachloride or methanol solutions. The analyte responses were
      compared and the statistical results revealed the feasibility of direct analysis
      of the extracted samples in carbon tetrachloride, resulting in a convenient
      methodology. The coupled method of DLLME-CD-IMS was exhaustively validated in
      terms of sensitivity, dynamic range, recovery, and enrichment factor. Finally,
      various real samples of apple, river and underground water were analyzed, all
      verifying the feasibility and success of the proposed method for the easy
      extraction of the analyte using DLLME separation before the direct analysis by CD
      IMS. 

PMID- 24742533
TI  - Preparation of an internal surface reversed-phase restricted-access material for
      the analysis of hydrophobic molecules in biological matrices.
AB  - Restricted-access materials (RAMs) have been broadly used for sample pretreatment
      in the chromatographic analysis of biological samples. In the present work, a
      novel internal surface reversed-phase (ISRP) RAM was prepared via surface
      initiated atom transfer radical polymerization (SI-ATRP). Octadecyl and 4
      (chloromethyl)phenyl were immobilized on silica using a one-pot synthesis
      approach to form a reversed-phase layer to retain small hydrophobic molecules,
      allowing the modified silica to serve as a macro-initiator. Then, poly(glycidyl
      methacrylate) (pGMA) was grafted onto the surface via SI-ATRP, and the epoxy
      groups were further hydrolyzed to form an external hydrophilic layer. The
      properties of this ISRP-RAM for the retention of small molecules and the
      exclusion of proteins were evaluated using solid-phase extraction (SPE). The
      removal efficiencies of bovine serum albumin (BSA) and lysozyme were 94.9% and
      93.5%, respectively. The recoveries of five drugs, puerarin, p
      hydroxybenzaldehyde, loratadine, nifedipine and diazepam, were 93.2-116%.
      Furthermore, the ISRP-RAM was employed for the SPE of five phthalate esters
      (PAEs) from bovine milk prior to high-performance liquid chromatography (HPLC)
      analysis. The results indicate that the prepared ISRP-RAM is qualified for
      practical bioanalysis. 

PMID- 24742535
TI  - A feasibility study of the Tehran research reactor as a neutron source for BNCT.
AB  - Investigation on the use of the Tehran Research Reactor (TRR) as a neutron source
      for Boron Neutron Capture Therapy (BNCT) has been performed by calculating and
      measuring energy spectrum and the spatial distribution of neutrons in all
      external irradiation facilities, including six beam tubes, thermal column, and
      the medical room. Activation methods with multiple foils and a copper wire have
      been used for the mentioned measurements. The results show that (1) the small
      diameter and long length beam tubes cannot provide sufficient neutron flux for
      BNCT; (2) in order to use the medical room, the TRR core should be placed in the
      open pool position, in this situation the distance between the core and patient
      position is about 400 cm, so neutron flux cannot be sufficient for BNCT; and (3)
      the best facility which can be adapted for BNCT application is the thermal
      column, if all graphite blocks can be removed. The epithermal and fast neutron
      flux at the beginning of this empty column are 4.12*10(9) and 1.21*10(9)
      n/cm(2)/s, respectively, which can provide an appropriate neutron beam for BNCT
      by designing and constructing a proper Beam Shaping Assembly (BSA) structure.

PMID- 24742536
TI  - Facilitating culture-centered communication between health care providers and
      veterans transitioning from military deployment to civilian life.
AB  - OBJECTIVE: To describe returning veterans' transition experience from military to
      civilian life and to educate health care providers about culture-centered
      communication that promotes readjustment to civilian life. METHODS: Qualitative,
      in-depth, semi-structured interviews with 17 male and 14 female Iraq and
      Afghanistan veterans were audio recorded, transcribed verbatim, and analyzed
      using Grounded Practical Theory. RESULTS: Veterans described disorientation when
      returning to civilian life after deployment. Veterans' experiences resulted from
      an underlying tension between military and civilian identities consistent with
      reverse culture shock. Participants described challenges and strategies for
      managing readjustment stress across three domains: intrapersonal,
      professional/educational, and interpersonal. CONCLUSIONS: To provide patient
      centered care to returning Iraq and Afghanistan veterans, health care providers
      must be attuned to medical, psychological, and social challenges of the
      readjustment experience, including reverse culture shock. Culture-centered
      communication may help veterans integrate positive aspects of military and
      civilian identities, which may promote full reintegration into civilian life.
      PRACTICE IMPLICATIONS: Health care providers may promote culture-centered
      interactions by asking veterans to reflect about their readjustment experiences.
      By actively eliciting challenges and helping veterans' to identify possible
      solutions, health care providers may help veterans integrate military and
      civilian identities through an increased therapeutic alliance and social support
      throughout the readjustment process.

PMID- 24742537
TI  - High prevalence of hepatitis B non-immunity in paediatric non-alcoholic fatty
      liver disease patients.

PMID- 24742539
TI  - Annual Review of Competence Progression (ARCP) performance of doctors who passed
      Professional and Linguistic Assessments Board (PLAB) tests compared with UK
      medical graduates: national data linkage study.
AB  - OBJECTIVE: To determine whether use of the Professional and Linguistic
      Assessments Board (PLAB) examination system used to grant registration for
      international medical graduates results in equivalent postgraduate medical
      performance, as evaluated at Annual Review of Competence Progression (ARCP),
      between UK based doctors who qualified overseas and those who obtained their
      primary medical qualification from UK universities. DESIGN: Observational study
      linking ARCP outcome data from the UK deaneries with PLAB test performance and
      demographic data held by the UK General Medical Council (GMC). SETTING: Doctors
      in postgraduate training for a medical specialty or general practice in the UK
      and doctors obtaining GMC registration via the PLAB system. PARTICIPANTS: 53,436
      UK based trainee doctors with at least one competency related ARCP outcome
      reported during the study period, of whom 42,017 were UK medical graduates and
      11,419 were international medical graduates who were registered following a pass
      from the PLAB route. MAIN OUTCOME MEASURE: Probability of obtaining a poorer
      versus a more satisfactory category of outcome at ARCP following successful
      registration as a doctor in the UK. RESULTS: International medical graduates were
      more likely to obtain a less satisfactory outcome at ARCP compared with UK
      graduates. This finding persisted even after adjustment for the potential
      influence of sex, age, years of UK based practice, and ethnicity and exclusion of
      outcomes associated with postgraduate examination failure (odds ratio 1.63, 95%
      confidence interval 1.30 to 2.06). However, international medical graduates who
      scored in the highest twelfth at part 1 of the PLAB (at least 32 points above the
      pass mark) had ARCP outcomes that did not differ significantly from those of UK
      graduates. CONCLUSIONS: These findings suggest that the PLAB test used for
      registration of international medical graduates is not generally equivalent to
      the requirements for UK graduates. The differences in postgraduate performance,
      as captured at ARCP, following the two routes to registration might be levelled
      out by raising the standards of English language competency required as well as
      the pass marks for the two parts of the PLAB test. An alternative might be to
      introduce a different testing system.

PMID- 24742540
TI  - A Comparison of In-person, Telephone, and Secure Messaging for Type 2 Diabetes
      Self-Management Support.
AB  - : Ongoing interaction between diabetes educators and patients is necessary for
      making and sustaining behavior changes essential for glycemic control and
      subsequently reducing the complications of diabetes. PURPOSE: The purpose of this
      study was to determine the feasibility of diabetes self-management support (DSMS)
      delivered via telephone or secure message and to compare clinical outcomes (A1C,
      LDL), behavioral goal achievement, and health maintenance task completion.
      METHODS: In sum, 150 persons with type 2 diabetes who completed diabetes self
      management education self-selected DSMS methods: 1 in-person visit (n = 47), 3
      brief visits by phone (n = 44), or 3 by secure message (n = 59) through
      electronic health record. DSMS included evaluation of goal achievement, barriers
      and facilitators, problem solving, and review of health maintenance exams. Self
      reported data were collected at 9 months. RESULTS: There were no significant
      differences among groups in main outcomes between baseline and 9-month follow-up.
      Behavioral goals were achieved by 59% of in-person participants, 73% phone, and
      77% secure message. Sixty-two completed the intervention per protocol: fewer
      online than in-person or phone groups. Mean attempts to contact participants was
      significantly greater in the secure message group. Phone contact was
      significantly longer than secure message. CONCLUSIONS: Telephone and secure
      message was feasible for providing DSMS. Three brief contacts by phone or secure
      message resulted in similar outcomes when compared to an in-person visit. Secure
      messaging required less staff time, but increased patient engagement is needed.

PMID- 24742541
TI  - Unraveling the complexities of cardiac remodeling and hypertrophy - high-content
      screening and computational modeling.

PMID- 24742542
TI  - Arg25Pro (c.915G>C) polymorphism of transforming growth factor beta1 gene
      increases the risk of developing Graves' disease.
AB  - BACKGROUND: Graves' disease (GD) arises due to complex interactions between
      genetic and environmental factors. Transforming growth factor beta1 (TGFbeta1) is
      required to maintain immune homeostasis, and is implicated in lymphocyte
      infiltration, thyroid follicular cell hyperplasia, and production of autoantibody
      in the thyroid gland of patients with GD. AIM: The aim of the present study was
      to investigate the possible association of Leu10Pro (c.869T>C) and Arg25Pro
      (c.915G>C) single nucleotide polymorphisms (SNPs) of TGFbeta1 gene with the
      occurrence of GD. METHODS: We analyzed the genotype and allele frequencies of
      these SNPs in 171 patients with GD and 197 healthy controls using PCR-restriction
      fragment length polymorphism (RFLP). RESULTS: The distribution of Leu10Pro
      (c.869T>C) genotype and allele frequencies in the control and GD groups were not
      significantly different. However, there was a significant increase of Arg25Pro
      (c.915G>C) C allele frequency in patients with GD compared with healthy controls
      (p<0.0001, OR=4.77, 95% CI=3.32-7.03). In addition, C allele carrying subjects
      (CG+CC) had 5.31-fold increased risk for developing GD according to GG
      homozygotes (p<0.0001, 95% CI=3.43-8.44). No association between polymorphisms
      and GD phenotypes was observed. CONCLUSION: This study indicates that the
      Arg25Pro (c.915G>C) polymorphism of TGFbeta1 gene may be related to occurrence of
      GD.

PMID- 24742543
TI  - Benign cystic neoplasm and endocrine tumours of the pancreas--when and how to
      operate--an overview.
AB  - BACKGROUND: The recent evolution of limited local operative procedures for benign
      pancreatic lesions shifted surgical treatment options to the application of local
      techniques, although major resections of pancreatic head and left resection are
      still the standard. OBJECTIVES: To evaluate the level of evidence of tumour
      enucleation (EN), pancreatic middle segment resection (PMSR) and duodenum
      preserving total/subtotal pancreatic head resection (DPPHRt/s), we focus based on
      present knowledge on indication to surgical treatment evaluating the questions,
      when and how to operate. RESULTS: Tumour enucleation is recommended for all
      symptomatic neuro-endocrine tumours with size up to 2-3 cm and non-adherence to
      pancreatic main-ducts. EN has been applied predominantly in neuro-endocrine
      tumours and less frequently in cystic neoplasms. 20% of enucleation are performed
      as minimal invasive laparascopic procedure. Surgery related severe post-operative
      complications with the need of re-intervention are observed in about 11%,
      pancreatic fistula in 33%. The major advantage of EN are low procedure related
      early post-operative morbidity and a very low hospital mortality. PMSR is applied
      in two thirds for symptomatic cystic neoplasm and in one third for neuro
      endocrine tumours. The high level of 33% pancreatic fistula and severe post
      operative complications of 18% is related to management of proximal pancreatic
      stump. DPPHRt/s is used in 70% for symptomatic cystic neoplasms, for lesions with
      risk for malignancy and in less than 10% for neuro-endocrine tumours. DPPHRt with
      segment resection of peripapillary duodenum and intra-pancreatic common bile duct
      has been applied in one third of patients and in two thirds by complete
      preservation of duodenum and common bile duct. The level of evidence for EN and
      PMSR is low because of retrospective data evaluation and absence of RCT results.
      For DPPHR, 7 prospective, controlled studies underline the advantages compared to
      partial pancreaticoduodenectomy. CONCLUSION: The application of tumour
      enucleation, pancreatic middle segment resection and duodenum preserving subtotal
      or total pancreatic head resection are associated with low level surgery related
      early post-operative complications and a very low hospital mortality. The major
      advantage of the limited procedures is preservation of exo- and endocrine
      pancreatic functions.

PMID- 24742544
TI  - Remediation of polybrominated diphenyl ethers in soil using Ni/Fe bimetallic
      nanoparticles: influencing factors, kinetics and mechanism.
AB  - Polybrominated diphenyl ethers (PBDEs) are commonly used as additive flame
      retardants in all kinds of electronic products. PBDEs are now ubiquitous in the
      environment, with soil as a major sink, especially in e-waste recycling sites.
      This study investigated the degradation of decabromodiphenyl ether (BDE209) in a
      spiked soil using Ni/Fe bimetallic nanoparticles. The results indicated that
      Ni/Fe bimetallic nanoparticles are able to degrade BDE209 in soil at ambient
      temperature and the removal efficiency can reach 72% when an initial pH of 5.6
      and at a Ni/Fe dosage of 0.03 g/g. A declining trend in degradation was noticed
      with decreasing Ni loading and increasing of initial BDE209 concentration. The
      degradation products of BDE209 were analyzed by GC-MS, which showed that the
      degradation of BDE209 was a process of stepwise debromination from nBr to (n
      1)Br. And a possible debromination pathway was proposed. At last, the degradation
      process was analyzed as two-step mechanism, mass transfer and reaction. This
      current study shows the potential ability of Ni/Fe nanoparticles to be used for
      removal of PBDEs in contaminated soil.

PMID- 24742545
TI  - Assessment of anticoagulant rodenticide exposure in six raptor species from the
      Canary Islands (Spain).
AB  - Anticoagulant rodenticides are highly toxic compounds that are widely used for
      pest control of rodents, but that also may threaten the wildlife's health. This
      work aimed to assess the exposure to first- and second-generation anticoagulant
      rodenticides (ARs) in six birds of prey species from the Canary Islands (Spain).
      The concentrations of seven widely used ARs were determined by LC-MS/MS in 104
      liver samples of six species of birds of prey (Buteo buteo, Accipiter nisus,
      Falco pelegrinoides, Falco tinnunculus, Asio otus, and Tyto alba). We determined
      that 61% of the livers had detectable residues of at least one AR. The most
      frequently detected AR was bromadiolone, which was detected in 60.3% of the
      positive cases. The detection frequencies of these compounds varied widely,
      depending on the species. More than 75% of the A. nisus, T. alba, and A. otus
      individuals had detectable rodenticide residues in the liver. However, F.
      tinnunculus exhibited the highest concentrations of AR, with median values above
      100 ng/g w.w. We did not detect first-generation ARs in any of the samples. When
      grouped, nocturnal species exhibited higher AR concentrations than diurnal
      species (P<0.001). The residue levels were higher among small mammal-eaters than
      bird-eaters (P<0.01). While most animals exhibited no macroscopic signs of
      coagulation disorders, approximately 35% exceeded the threshold levels of
      toxicity, which suggests that these compounds could weaken these animals in their
      natural environment. In conclusion, the control of rodent populations by ARs
      suggests that these compounds will enter the food chain and thus threaten the
      vulnerable populations of raptors on the Canary Islands. Our findings require
      authorities to ban or strictly control the use of these rodenticides in the
      natural environment for the conservation of raptors and other predatory species.

PMID- 24742546
TI  - A twenty-one year temporal trend of persistent organic pollutants in St. Lawrence
      Estuary beluga, Canada.
AB  - Persistent organic pollutants (POPs) were measured in blubber from 144 stranded
      adult belugas (Delphinapterus leucas) found on the shores of the St. Lawrence
      Estuary (SLE) between 1987 and 2007. Temporal trends of POP concentrations (ln
      transformed) in beluga were described by three models, zero slope (ZS), linear
      (L) and two-segment piecewise (PW). Often two but sometimes all three models were
      equivalent in describing temporal trends based on Akaike's Information Criterion
      for small sample sizes. Over this 21-year time period, concentrations of most
      legacy POPs, including PCBs, DDTs and HCHs, exhibited relatively weak (<=11% per
      year) but significant decreasing trends in beluga. For PBDEs, temporal trends
      were best described by a PW model, characterizing a rapid increase until 1997
      1998 followed by a slower increase for males and a steady-state for females.
      Potential cofactors such as blubber lipid content and carcass state of
      preservation did not show any significant temporal trends over the time period
      considered. Nitrogen stable isotope ratios (delta(15)N) in beluga liver, a proxy
      of trophic level, could not be associated to any effect on temporal trends of POP
      concentrations in beluga. Several POPs exhibited significant relationships with
      age of beluga and data were age-adjusted. Temporal trends of POP concentrations
      adjusted for age of beluga were reassessed but results were essentially identical
      as those obtained with the original POP data. Overall, POP temporal trends
      observed in SLE beluga are consistent with changes expected from regulations and
      restrictions in the use of these compounds in developed countries.

PMID- 24742547
TI  - Health risk assessment linked to filling coastal quarries with treated dredged
      seaport sediments.
AB  - Dredged seaport sediments raise complex management problems since it is no longer
      possible to discharge them into the sea. Traditional waste treatments are poorly
      adapted for these materials in terms of absorbable volumes and cost. In this
      context, filling quarries with treated sediments appears interesting but its
      safety regarding human health must be demonstrated. To achieve this, a specific
      methodology for assessing health risks has been developed and tested on three
      seaport sediments. This methodology includes the development of a conceptual
      model of the global scenario studied and the definition of specific protocols for
      each of its major steps. The approach proposed includes in particular the use of
      metrological and experimental tools that are new in this context: (i) an
      experimental lysimeter for characterizing the deposit emissions, and (ii) a
      geological radar for identifying potential preferential pathways between the
      sediment deposit and the groundwater. The application of this approach on the
      three sediments tested for the scenario studied showed the absence of health risk
      associated with the consumption of groundwater for substances having a "threshold
      effect" (risk quotient <1), and an acceptable risk for substances having a "non
      threshold effect", with the notable exception of arsenic (individual risk equal
      to 3.10(-6)). 

PMID- 24742548
TI  - Public health benefits of reducing air pollution in Shanghai: a proof-of-concept
      methodology with application to BenMAP.
AB  - In recent years, levels of particulate matter (PM) air pollution in China have
      been relatively high, exceeding China's Class II standards in many cities and
      impacting public health. This analysis takes Chinese health impact functions and
      underlying health incidence, applies 2010-2012 modeled and monitored PM air
      quality data, and estimates avoided cases of mortality and morbidity in Shanghai,
      assuming achievement of China's Class II air quality standards. In Shanghai, the
      estimated avoided all cause mortality due to PM10 ranged from 13 to 55 cases per
      day and from 300 to 800 cases per year. The estimated avoided impact on hospital
      admissions due to PM10 ranged from 230 cases to 580 cases per day and from 5400
      to 7900 per year. The estimated avoided impact on all cause mortality due to
      PM2.5 ranged from 6 to 26 cases per day and from 39 to 1400 per year. The
      estimated impact on all cause mortality of a year exposure to an annual or
      monthly mean PM2.5 concentration ranged from 180 to 3500 per year. In Shanghai,
      the avoided cases of all cause mortality had an estimated monetary value ranging
      from 170 million yuan (1 US dollar=4.2 yuan Purchasing Power Parity) to 1200
      million yuan. Avoided hospital admissions had an estimated value from 20 to 43
      million yuan. Avoided emergency department visits had an estimated value from 5.6
      million to 15 million yuan. Avoided outpatient visits had an estimated value from
      21 million to 31 million yuan. In this analysis, available data were adequate to
      estimate avoided health impacts and assign monetary value. Sufficient supporting
      documentation was available to construct and format data sets for use in the
      United States Environmental Protection Agency's health and environmental
      assessment model, known as the Environmental Benefits Mapping and Analysis
      Program - Community Edition ("BenMAP-CE").

PMID- 24742549
TI  - Metal(loid) allocation and nutrient retranslocation in Pinus halepensis trees
      growing on semiarid mine tailings.
AB  - The goal of this study was to evaluate internal metal(loid) cycling and the risk
      of metal(loid) accumulation in litter from Pinus halepensis trees growing at a
      mine tailing disposal site in semiarid Southeast Spain. Internal nutrient
      retranslocation was also evaluated in order to gain insight into the ability of
      pine trees to cope with the low-fertility soil conditions at the tailings. We
      measured metal(loid) concentrations in the foliage (young and old needles), woody
      stems and fresh leaf litter of pine trees growing on tailings. The nutrient
      status and stable isotope composition of pine foliage (delta(13)C, delta(15)N,
      delta(18)O as indicators of photosynthesis and water use efficiency) were also
      analyzed. Tailing soil properties in vegetation patches and in adjacent bare soil
      patches were characterized as well. Significant amounts of metal(loid)s such us
      Cd, Cu, Pb and Sb were immobilized in the woody stems of Pinus halepensis trees
      growing on tailings. Leaf litterfall showed high concentrations of As, Cd, Sb, Pb
      and Zn, which thereby return to the soil. However, water extractable metal(loid)
      concentrations in tailing soils were similar between vegetation patches (mineral
      soil under the litter layer) and bare soil patches. The pines growing on mine
      tailings showed very low foliar P concentrations in all leaf age classes, which
      suggests severe P deficiency. Young (current year) needles showed lower
      accumulation of metal(loid)s, higher nutrient concentrations (P and K), and
      higher water use efficiency (as indicated by and delta(13)C and delta(18)O data)
      than older needles. Substantial nutrient resorption occurred before leaf
      litterfall, with 46% retranslocation efficiency for P and 89% for K. In
      conclusion, phytostabilization of semiarid mine tailings with Pinus halepensis is
      feasible but would require careful monitoring of the trace elements released from
      litterfall, in order to assess the long term risk of metal(loid) transfer to the
      food chain. 

PMID- 24742550
TI  - Enantioselective toxicity, bioaccumulation and degradation of the chiral
      insecticide fipronil in earthworms (Eisenia feotida).
AB  - The enantioselective acute toxicity to earthworms of racemic fipronil and its
      individual enantiomers was studied. R-(-)-fipronil was approximately 1.5 times
      more toxic than the racemate and approximately 2 times more toxic than S-(+)
      fipronil after 72 and 96 h of exposure, respectively. Assays of fipronil
      enantiomer bioaccumulation and degradation in earthworms were conducted. The bio
      concentration factors (BCFs) were slightly different between the two enantiomers.
      The enantiomeric fraction (EF) values in earthworms in the bioaccumulation period
      were approximately 0.5, which indicated there was no enantioselective
      bioaccumulation. In contrast, the degradation of fipronil in earthworms was
      enantioselective: the t1/2 values for R- and S-fipronil were 3.3 and 2.5 days,
      respectively, in natural soil, and 2.1 and 1.4 days, respectively, in artificial
      soil. The results of soil analyses showed that the degradation of fipronil was
      not enantioselective, which suggested that the enantioselectivity of fipronil in
      earthworms results from the organism's metabolism. The study also demonstrated
      that the presence of earthworms could accelerate the degradation of fipronil in
      soil.

PMID- 24742551
TI  - Determining the relative sensitivity of benthic diatoms to atrazine using rapid
      toxicity testing: a novel method.
AB  - Herbicides pose a potential threat to aquatic ecosystems, especially to
      phototrophic organisms such as benthic diatoms. Benthic diatoms may be a valuable
      indicator of the toxic impacts of herbicides in aquatic systems. However, this
      requires information on the herbicide sensitivity of a wide range of freshwater
      benthic diatom taxa. Unfortunately this information is only available for a
      limited number of species as current methods of developing new algae toxicity
      tests on individual taxa are lengthy and costly. To address this issue, we
      developed a new rapid toxicity test method to test natural benthic communities,
      from which the relative herbicide sensitivity of many individual taxa can be
      derived. This involved the collection of natural benthic communities from rocks
      in situ, which were placed directly into laboratory toxicity tests. Sensitivity
      data for several diatom genera in a 48 hour exposure toxicity test were produced,
      without the need for cultures or multiple site visits. After exposure to the
      highest treatment of atrazine (500 MUg L(-1)) there were significant declines of
      healthy cells in the most sensitive genera: Gomphonema declined by 74%, Amphora
      by 62%, Cymbella by 54% and Ulnaria by 34% compared to control levels. In
      contrast, the genera, Eunotia, Achnanthidium and Navicula, had no statistically
      significant decline in cell health. This method can identify the diatom taxa most
      at risk of herbicide toxicity within the natural benthic diatom community. The
      rapid toxicity testing method presented is a simple and effective method to
      obtain sensitivity data for multiple taxa within a natural benthic diatom
      community in a relatively short period of time.

PMID- 24742552
TI  - Lead in rice: analysis of baseline lead levels in market and field collected rice
      grains.
AB  - In a large scale survey of rice grains from markets (13 countries) and fields (6
      countries), a total of 1578 rice grain samples were analysed for lead. From the
      market collected samples, only 0.6% of the samples exceeded the Chinese and EU
      limit of 0.2 MUg g(-1) lead in rice (when excluding samples collected from known
      contaminated/mine impacted regions). When evaluating the rice grain samples
      against the Food and Drug Administration's (FDA) provisional total tolerable
      intake (PTTI) values for children and pregnant women, it was found that only
      people consuming large quantities of rice were at risk of exceeding the PTTI from
      rice alone. Furthermore, 6 field experiments were conducted to evaluate the
      proportion of the variation in lead concentration in rice grains due to genetics.
      A total of 4 of the 6 field experiments had significant differences between
      genotypes, but when the genotypes common across all six field sites were
      assessed, only 4% of the variation was explained by genotype, with 9.5% and 11%
      of the variation explained by the environment and genotype by environment
      interaction respectively. Further work is needed to identify the sources of lead
      contamination in rice, with detailed information obtained on the locations and
      environments where the rice is sampled, so that specific risk assessments can be
      performed.

PMID- 24742553
TI  - Heterogeneity in ragweed pollen exposure is determined by plant composition at
      small spatial scales.
AB  - Pollen allergies are one of the most common health problems in the United States
      and over 20% of Americans are sensitized to the pollen produced by common ragweed
      (Ambrosia artemisiifolia L.). Despite the importance of allergenic pollen to
      public health, no research has linked land use and plant populations to spatial
      heterogeneity in airborne pollen concentrations. In order to quantify these
      relationships and elucidate the processes which lead to pollen exposure, we
      surveyed ragweed stem density in Detroit (Michigan, USA) as a function of land
      use. We then deployed 34 pollen collectors throughout the city and recorded
      ragweed cover in the immediate vicinity of each pollen collector. We found that
      ragweed populations were highest in vacant lots, a common land cover type in
      Detroit. Because ragweed population density was so strongly correlated to vacant
      lots, for which spatially explicit data were available, we were able to
      investigate whether observed ragweed pollen concentrations were a function of
      land use at the spatial scales of 10 m and 1 km. Both relationships were
      significant, and the combination of these two variables predicts a large portion
      of airborne ragweed pollen concentrations (R(2)=0.48). These results emphasize
      the important role of pollen production within the urban environment and show
      that management of allergenic pollen producing plants must be considered at
      multiple spatial scales. Our findings also demonstrate that there is too much
      spatial heterogeneity for a pollen collector at any given site to portray the
      allergenic pollen load experienced by different individuals within the same city.
      Finally, we discuss how spatial correlations between socio-economic status,
      vacant lots, and ragweed could help to explain the disproportionate amount of
      allergies and ragweed sensitization experienced by low income and minority
      populations in Detroit.

PMID- 24742554
TI  - Metal and nanoparticle occurrence in biosolid-amended soils.
AB  - Metals can accumulate in soils amended with biosolids in which metals have been
      concentrated during wastewater treatment. The goal of this study is to inspect
      agricultural sites with long-term biosolid application for a suite of regulated
      and unregulated metals, including some potentially present as commonly used
      engineered nanomaterials (ENMs). Sampling occurred in fields at a municipal and a
      privately operated biosolid recycling facilities in Texas. Depth profiles of
      various metals were developed for control soils without biosolid amendment and
      soils with different rates of biosolid application (6.6 to 74 dry tons per
      hectare per year) over 5 to 25 years. Regulated metals of known toxicity,
      including chromium, copper, cadmium, lead, and zinc, had higher concentrations in
      the upper layer of biosolid-amended soils (top 0-30 cm or 0-15 cm) than in
      control soils. The depth profiles of unregulated metals (antimony, hafnium,
      molybdenum, niobium, gold, silver, tantalum, tin, tungsten, and zirconium)
      indicate higher concentrations in the 0-30 cm soil increment than in the 70-100
      cm soil increment, indicating low vertical mobility after entering the soils.
      Titanium-containing particles between 50 nm and 250 nm in diameter were
      identified in soil by transmission electron microscopy (TEM) coupled with energy
      dispersive x-ray spectroscopy (EDX) analysis. In conjunction with other studies,
      this research shows the potential for nanomaterials used in society that enter
      the sewer system to be removed at municipal biological wastewater treatment
      plants and accumulate in agricultural fields. The metal concentrations observed
      herein could be used as representative exposure levels for eco-toxicological
      studies in these soils.

PMID- 24742555
TI  - Nitrogen deposition in Spain: modeled patterns and threatened habitats within the
      Natura 2000 network.
AB  - The Mediterranean Basin presents an extraordinary biological richness but very
      little information is available on the threat that air pollution, and in
      particular reactive nitrogen (N), can pose to biodiversity and ecosystem
      functioning. This study represents the first approach to assess the risk of N
      enrichment effects on Spanish ecosystems. The suitability of EMEP and CHIMERE air
      quality model systems as tools to identify those areas where effects of
      atmospheric N deposition could be occurring was tested. For this analysis, wet
      deposition of NO3(-) and NH4(+) estimated with EMEP and CHIMERE model systems
      were compared with measured data for the period 2005-2008 obtained from different
      monitoring networks in Spain. Wet N deposition was acceptably predicted by both
      models, showing better results for oxidized than for reduced nitrogen,
      particularly when using CHIMERE. Both models estimated higher wet deposition
      values in northern and northeastern Spain, and decreasing along a NE-SW axis.
      Total (wet+dry) nitrogen deposition in 2008 reached maxima values of 19.4 and
      23.0 kg N ha(-1) year(-1) using EMEP and CHIMERE models respectively. Total N
      deposition was used to estimate the exceedance of N empirical critical loads in
      the Natura 2000 network. Grassland habitats proved to be the most threatened
      group, particularly in the northern alpine area, pointing out that biodiversity
      conservation in these protected areas could be endangered by N deposition. Other
      valuable mountain ecosystems can be also threatened, indicating the need to
      extend atmospheric deposition monitoring networks to higher altitudes in Spain.

PMID- 24742556
TI  - Pathways and consequences of contaminant flux to Acadian flycatchers (Empidonax
      virescens) in urbanizing landscapes of Ohio, USA.
AB  - A prevalent environmental contaminant, mercury (Hg) is mobile and persistent in
      aquatic systems, where it often occurs in its bioavailable form methylmercury.
      Because methylmercury can bioaccumulate in aquatic insects and then transfer to
      terrestrial food webs, riparian consumers reliant upon aquatic emergent insects,
      should be disproportionately affected. Using the aerial insectivore Acadian
      flycatcher (Empidonax virescens) as a focal species, we examined (1) the extent
      to which total Hg loads in breeding flycatchers affected body condition and
      reproductive output and (2) potential pathways of contaminant flux in 19 riparian
      forest fragments distributed across an urban-to-rural landscape gradient in Ohio,
      USA. From April-August 2011-2012, we collected blood samples from adult (n=76)
      and nestling (n=17 from 7 nests) flycatchers, monitored their annual reproductive
      success (i.e., total number of fledglings), and sampled water, sediment, and
      aquatic emergent insects at each site. Hg concentrations in adult flycatcher
      blood (47 to 584 MUg/kg, x-=211.8, SD=95.5) were low relative to published
      advisory levels and not related to body condition. However, even at low
      concentrations, blood Hg was negatively related to reproductive success, with a
      0.83 decline in the number of fledglings per MUg/kg (loge) increase of blood Hg.
      Adult flycatchers had 11* greater concentrations of blood Hg than their
      offspring. Hg levels in flycatcher blood were not predicted by Hg concentrations
      in sediment, water, or aquatic emergent insects, with the exception of rural
      landscapes alone, in which flycatcher Hg was negatively related to sediment Hg.
      In addition to illustrating the difficulty of predicting exposure pathways that
      may vary among landscape contexts, our study provides evidence that even trace
      levels of contaminants may impair reproductive success of free-living songbirds.

PMID- 24742557
TI  - Sprinkler irrigation of rice fields reduces grain arsenic but enhances cadmium.
AB  - Previous studies have demonstrated that rice cultivated under flooded conditions
      has higher concentrations of arsenic (As) but lower cadmium (Cd) compared to rice
      grown in unsaturated soils. To validate such effects over long terms under
      Mediterranean conditions a field experiment, conducted over 7 successive years
      was established in SW Spain. The impact of water management on rice production
      and grain arsenic (As) and cadmium (Cd) was measured, and As speciation was
      determined to inform toxicity evaluation. Sprinkler irrigation was compared to
      traditional flooding. Both irrigation techniques resulted in similar grain yields
      (~3000 kg grain ha(-1)). Successive sprinkler irrigation over 7 years decreased
      grain total As to one-sixth its initial concentration in the flooded system (0.55
      to 0.09 mg As kg(-1)), while one cycle of sprinkler irrigation also reduced grain
      total As by one-third (0.20 mg kg(-1)). Grain inorganic As concentration
      increased up to 2 folds under flooded conditions compared to sprinkler irrigated
      fields while organic As was also lower in sprinkler system treatments, but to a
      lesser extent. This suggests that methylation is favored under water logging.
      However, sprinkler irrigation increased Cd transfer to grain by a factor of 10,
      reaching 0.05 mg Cd kg(-1) in 7 years. Sprinkler systems in paddy fields seem
      particularly suited for Mediterranean climates and are able to mitigate against
      excessive As accumulation, but our evidence shows that an increased Cd load in
      rice grain may result.

PMID- 24742558
TI  - Integrated hydrological and water quality model for river management: a case
      study on Lena River.
AB  - The Hydrologic Simulation Program FORTRAN (HSPF) model was used to assess the
      impact of wastewater discharges on the water quality of a Lis River tributary
      (Lena River), a 176 km(2) watershed in Leiria region, Portugal. The model
      parameters obtained in this study, could potentially serve as reference values
      for the calibration of other watersheds in the area or with similar climatic
      characteristics, which don't have enough data for calibration. Water quality
      constituents modeled in this study included temperature, fecal coliforms,
      dissolved oxygen, biochemical oxygen demand, total suspended solids, nitrates,
      orthophosphates and pH. The results were found to be close to the average
      observed values for all parameters studied for both calibration and validation
      periods with percent bias values between -26% and 23% for calibration and -30%
      and 51% for validation for all parameters, with fecal coliforms showing the
      highest deviation. The model revealed a poor water quality in Lena River for the
      entire simulation period, according to the Council Directive concerning the
      surface water quality intended for drinking water abstraction in the Member
      States (75/440/EEC). Fecal coliforms, orthophosphates and nitrates were found to
      be 99, 82 and 46% above the limit established in the Directive. HSPF was used to
      predict the impact of point and nonpoint pollution sources on the water quality
      of Lena River. Winter and summer scenarios were also addressed to evaluate water
      quality in high and low flow conditions. A maximum daily load was calculated to
      determine the reduction needed to comply with the Council Directive 75/440/EEC.
      The study showed that Lena River is fairly polluted calling for awareness at
      behavioral change of waste management in order to prevent the escalation of these
      effects with especially attention to fecal coliforms.

PMID- 24742559
TI  - Bioaccumulation and effects of metals and trace elements from aquatic disposal of
      coal combustion residues: recent advances and recommendations for further study.
AB  - Advances have been made recently in assessing accumulation and effects of coal
      combustion residues (CCR). I provide a brief review of recent advancements,
      provide a tabulated summary of results of recent work, and put forth
      recommendations for future studies. One advancement is that mercury accumulation
      has begun to receive (limited) attention, whereas it had rarely been considered
      in the past. Additionally, some constituents of CCR have been shown to be
      accumulated by adults and transferred to offspring, sometimes compromising
      offspring health. Studies have demonstrated that amphibians, possessing complex
      life cycles, may accumulate and transfer some contaminants to terrestrial
      systems. Some study has been given to molecular and cellular effects of CCR
      exposure, although these studies have been limited to invertebrates. Population
      models have also been applied to CCR affected systems and have shown that CCR may
      affect animal populations under some conditions. In light of these advancements,
      there are several topics that require further assessment. First, more attention
      to Hg and its dynamics in CCR affected systems is warranted. Hg can be highly
      accumulative and toxic under some conditions and may interact with other
      components of CCR (notably Se), perhaps altering accumulation and effects of the
      contaminant mixtures. Second, further investigation of maternal transfer and
      effects of CCR contaminants need to be conducted. These studies could benefit
      from incorporation of quantitative models to project impacts on populations.
      Finally, more attention to the organic constituents of CCR (PAHs) is required, as
      a focus on inorganic compounds only may restrict our knowledge of contaminant
      dynamics and effects as a whole. While further studies will shed light on some
      chemical and biological nuances of exposure and effect, information available to
      date from numerous study sites implicates CCR as a bulk effluent that presents
      risks of bioaccumulation and effects on organisms in aquatic systems. 

PMID- 24742560
TI  - Studies into the formation of PBDEs and PBDD/Fs in the iron ore sintering
      process.
AB  - Polybrominated diphenyl ethers (PBDEs) and polybrominated dibenzo-p-dioxins and
      furans (PBDD/Fs) were detected in stack emissions from UK sinter plants. The sum
      of 36 PBDE congeners was measured at a mean concentration of 295 ng/N m(3) with a
      standard deviation of 96 ng/N m(3). The mean PBDD/F concentrations were 0.14 ng
      WHO-TEQ/m(3) (range=0.03-0.39). PBDD/F emission concentrations were approximately
      ten times lower than their PCDD/F homologues. To understand the possible
      formation mechanisms of brominated organic species in iron ore sintering, both
      full-scale and laboratory experiments using an experimental sintering process
      were carried out. A complete PBDE mass balance was undertaken for a full scale
      sinter plant showing that PBDEs were already present in the raw materials such as
      iron ores and coke breeze and that a significant proportion of the PBDE inputs
      were actually destroyed during the process. A number of controlled experiments
      were conducted using a laboratory-scale sintering apparatus (sinter pot). These
      were designed to investigate: (a) mass balance of PBDEs during sintering, (b) the
      relationship between the availability of bromide (as KBr) and PBDE emissions, and
      (c) the influence of the availability of both bromide and PBDEs on PBDD/F
      formation. As observed in the full scale plant, the PBDEs already present in the
      raw materials were mostly destroyed during the process (79-96%) for all sinter
      pot experiments. Increasing amounts of KBr in the raw sinter mix did not result
      in a significant increase in PBDE formation suggesting that there was no PBDE
      formation in sintering via de novo synthesis. No relationship was observed
      between PBDE inputs and PBDD/F emissions indicating that PBDEs did not act as
      precursors for PBDD/Fs formation. Finally, PBDD/F formation was enhanced
      substantially with increasing amounts of KBr suggesting that their formation
      mechanism was similar to that of PCDD/Fs via de novo synthesis.

PMID- 24742561
TI  - Long-term sampling of dioxin-like substances from a clinker kiln stack using
      alternative fuels.
AB  - The aim of this work is to characterize atmospheric emissions of polychlorinated
      dibenzo-p-dioxins (PCDDs)/polychlorinated dibenzofurans (PCDFs) and dioxin-like
      polychlorinated biphenyls (dl-PCBs) from a cement production plant where the
      existing clinker production line was completely replaced by a new state-of-the
      art installation. The project started in April 2008 with the installation of a
      long-term sampling system in the stack of the clinker kiln that used petroleum
      coke as fuel; PCDD/PCDF and dl-PCB emissions were then evaluated for a two year
      period. To carry out the second part of the study, in 2010 the sampling system
      was moved to the new installation in which, apart from conventional fuel,
      recovered derived fuel (RDF) and WWTP sludge were used as alternative fuels. For
      both the old and new clinker kilns, PCDD/PCDF emission values were well below the
      limit established by the European Waste Incineration Directive 2000/76/CE (EWID)
      of 100 pg I-TEQ/Nm(3); values ranged from 0.43 to 2.02 and from 0.07 to 3.31 pg I
      TEQ/Nm(3), respectively. dl-PCBs accounted for approximately 25% of the WHO-TEQ
      toxicity. These results prove that the installation is capable of reducing
      PCDD/PCDF and dl-PCB emissions when alternative fuels are integrated into the
      process. In the case of PCDDs/PCDFs, the major contributions to total TEQ were
      usually from 2,3,7,8-TCDD (owing to its relative abundance) and 2,3,4,7,8-PeCDF
      (due to its high I-TEF of 0.5); while for dl-PCBs, the major contribution was
      from PCB-126. The slight shift in the congener profile between the old and new
      installations was characterized and a regression model was proposed for dl-PCB
      emissions depending on the RDF flow rate in the clinker.

PMID- 24742563
TI  - AGA institute guidelines for colonoscopy surveillance after cancer resection:
      clinical decision tool.

PMID- 24742562
TI  - Isolation and screened neuroprotective active constituents from the roots and
      rhizomes of Valeriana amurensis.
AB  - In previous study, we have screened the effective fraction against Alzheimer's
      disease (AD-EF) from the extracts of roots and rhizomes of Valeriana amurensis,
      based on which neuroprotective active constituents from AD-EF were investigated.
      Six new compounds 1-6, including four iridoids (xiecaoside A-C and xiecaoline A),
      one pinane-type monoterpeneglucoside (xiecaoside D), and one phenylpropanoid
      glycoside (xiecaoside E) were isolated together with 11 known compounds 7-17. The
      structures of 1-6 were elucidated by their spectroscopic data. The protective
      effects of compounds 1-17 on PC12 cells with neurotoxicity induced by amyloid
      beta 1-42 (Abeta(1-42)) was also investigated, respectively. Consequently,
      compound 6 and lignans 11-17 were responsible for protecting against Abeta
      induced toxicity in PC12 cells.

PMID- 24742564
TI  - [Pathologic diagnosis of colorectal cancer in the era of personalized therapy].

PMID- 24742565
TI  - [Comparative analysis of real-time quantitative PCR-Sanger sequencing method and
      TaqMan probe method for detection of KRAS/BRAF mutation in colorectal
      carcinomas].
AB  - OBJECTIVE: To compare the application values of real-time quantitative PCR-Sanger
      sequencing and TaqMan probe method in the detection of KRAS and BRAF mutations,
      and to correlate KRAS/BRAF mutations with the clinicopathological characteristics
      in colorectal carcinomas. METHODS: Genomic DNA of the tumor cells was extracted
      from formalin fixed paraffin embedded (FFPE) tissue samples of 344 colorectal
      carcinomas by microdissection. Real-time quantitative PCR-Sanger sequencing and
      TaqMan probe method were performed to detect the KRAS/BRAF mutations. The
      frequency and types of KRAS/BRAF mutations, clinicopathological characteristics
      and survival time were analyzed. RESULTS: KRAS mutations were detected in 39.8%
      (137/344) and 38.7% (133/344) of 344 colorectal carcinomas by using real-time
      quantitative PCR-Sanger sequencing and TaqMan probe method, respectively. BRAF
      mutation was detected in 4.7% (16/344) and 4.1% (14/344), respectively. There was
      no significant correlation between the two methods. The frequency of the KRAS
      mutation in female was higher than that in male (P < 0.05). The frequency of the
      BRAF mutation in colon was higher than that in rectum. The frequency of the BRAF
      mutation in stage III-IV cases was higher than that in stageI-II cases. The
      frequency of the BRAF mutation in signet ring cell carcinoma was higher than that
      in mucinous carcinoma and nonspecific adenocarcinoma had the lowest mutation
      rate. The frequency of the BRAF mutation in grade III cases was higher than that
      in grade II cases (P < 0.05). The overall concordance for the two methods of
      KRAS/BRAF mutation detection was 98.8% (kappa = 0.976). There was statistic
      significance between BRAF and KRAS mutations for the survival time of colorectal
      carcinomas (P = 0.039). There were no statistic significance between BRAF
      mutation type and BRAF/KRAS wild type (P = 0.058). CONCLUSIONS: (1) Compared with
      real-time quantitative PCR-Sanger sequencing, TaqMan probe method is better with
      regard to handling time, efficiency, repeatability, cost and equipment. (2) The
      frequency of the KRAS mutation is correlated with gender. BRAF mutation is
      correlated with primary tumor site, TNM stage, histological types and
      histological grades.(3) BRAF gene mutation is an independent prognostic marker
      for colorectal carcinomas.

PMID- 24742566
TI  - [HER2 protein testing in gastric cancer: a retrospective analysis of 1 471 cases
      during two different periods in a single medical center].
AB  - OBJECTIVE: To study the potential factors in influencing the performance of
      immunohistochemical testing for HER2 protein in gastric cancers. METHODS: The
      HER2 protein expression status of 1 471 surgically resected archival gastric
      cancer cases in Drum Tower Hospital collected during two different periods was
      retrospectively analyzed. The materials included 957 cases tested during the
      period from 2007 to 2009 (group 1) and 514 cases from 2012 to 2013 (group 2). The
      test procedures and results observed during these two periods were compared.
      RESULTS: The percentages of score 3 HER2 protein expression (14.4%, 74/514 versus
      9.5%, 91/957) and score 2 or score 3 HER2 protein expression (27.2%, 140/514
      versus 21.7%, 208/957) were both higher in group 2 than in group 1 (P < 0.05). In
      group 1, the cancer tissue was fixed in 10% formalin, stained manually with HER2
      antibody A0485 (Dako) and assessed by different pathologists.In group 2, the
      tissue was fixed in 10% neutral buffered formalin (pH 7.2), stained using
      automated immunostaining system (Roche Benchmark XT) with HER2 antibody 4B5
      (Ventana) and assessed by a specialized team of pathologists. CONCLUSION: The
      results of HER2 immunostaining in gastric cancer are influenced by a number of
      factors including type of fixative, clone number of primary antibody, staining
      methods and experience of pathologists.

PMID- 24742567
TI  - [MicroRNA expression signature profile and its clinical significance in
      endometrioid carcinoma].
AB  - OBJECTIVE: To determine the microRNA (miRNA) expression signature and its
      clinical significance in endometrioid carcinoma (EC). METHODS: The miRNA profiles
      were analyzed by miRNA microarray in 73 cases of EC. The expression level of the
      eight selected miRNAs were measured by real-time fluorescent quatitative PCR(qRT
      PCR). Immunohistochemistry (IHC) was performed to assess the status of PTEN, a
      potential target of the selected miRNAs. RESULTS: (1) Using TaqMan low-density
      arrays, 47 miRNAs that differed between EC and normal controls were identified,
      including 26 down-regulated and 21 up-regulated miRNAs. (2) To confirm the miRNA
      expression pattern in typeIEC, the expression levels of the eight selected miRNAs
      were evaluated in a new set of 58 cases of typeIEC by individual miRNA qRT-PCR
      assays. Three miRNAs (miR-141, miR-200a, miR-205) were up-regulated and two
      miRNAs (miR-143, miR-145) were down-regulated. These were significantly
      differentially expressed in typeIEC and normal controls (P < 0.05), whereas such
      difference was not present in type II tumors compared to normal controls. (3) In
      typeIEC, loss of PTEN was more frequent in the miR-141 or miR-200a up-regulated
      subgroups, and the correlation between the PTEN and miR-200a status in
      typeItumors was statistically significant (P < 0.05). CONCLUSIONS: EC may have a
      unique miRNA expression profile. The expression levels of the five miRNAs (miR
      141, miR-200a, miR-205, miR-143, miR-145) are significantly deregulated in
      typeIEC compared to normal control but not in typeIItumors. The findings suggest
      that the miRNAs related to type Iand typeIIEC might be different. PTEN might be a
      potential target of miR-141 and miR-200a in endometrial carcinogenesis.

PMID- 24742568
TI  - [ALK fusion gene assessment by fully automatic immunohistochemistry in non-small
      cell lung cancer].
AB  - OBJECTIVE: To evaluate the sensitivity and specificity of fully automated
      immunohistochemistry (IHC), with comparison to FISH, in the detection of EML4-ALK
      rearrangement in lung adenocarcinoma (ADC); and the use of IHC as a pre-screening
      tool. METHODS: A total of 404 paraffin-embedded NSCLC samples from surgical
      resections were tested by IHC with Ventana anti-ALK rabbit monoclonal antibody
      (D5F3) and ultrasensitive detection kit. ALK rearrangement was further confirmed
      by FISH. RESULTS: Twenty-nine of 404 lung ADCs (7.2%) were positive for ALK by
      IHC. ALK positive tumor cells demonstrated strong and diffused granular
      cytoplasmic staining. All the ALK IHC-positive cases were confirmed to harbor ALK
      rearrangement by FISH. None of the ALK IHC-negative cases was FISH-positive.
      CONCLUSIONS: IHC can effectively detect ALK rearrangement in lung cancer. It may
      provide a reliable and cost-effective diagnostic approach in routine pathologic
      laboratories for the identification of suitable candidates for ALK-targeted
      therapy.

PMID- 24742569
TI  - [Interdigitating dendritic cell sarcoma/tumor: a clinicopathologic study].
AB  - OBJECTIVE: To study the clinicopathologic characteristics and diagnostic criteria
      of interdigitating dendritic cell sarcoma/tumor (IDCS/T). METHODS: The clinical
      features, histologic findings and results of immunohistochemical study in six
      cases of IDCS/T were analyzed, with review of literature. RESULTS: The age of
      patients ranged from 20 to 68 years. The sites of involvement included lymph
      node, tonsil and soft tissue. Histologically, the tumor cells were arranged in
      sheets, fascicles or whorls and intimately admixed with abundant lymphocytes and
      plasma cells. They were oval to spindly in shape and contained pale eosinophilic
      cytoplasm, oval nuclei and distinct nucleoli.Immunohistochemical study showed
      that the tumor cells were positive for S-100 protein and CD68. CONCLUSIONS:
      IDCS/T is a rare malignant tumor with poor prognosis. It carries distinctive
      histologic pattern and immunophenotype. The entity needs to be distinguished from
      follicular dendritic cell sarcoma/tumor, anaplastic large cell lymphoma and other
      spindle cell sarcomas in occurring soft tissue.

PMID- 24742570
TI  - [Effects of CD147 gene silencing on protein expression of ANXA2, MMP-2 and TIMP-2
      by thyroid medullary carcinoma TT cells and biologic characteristics].
AB  - OBJECTIVE: To study the influence of CD147 gene silencing on the expression of
      ANXA2, MMP-2 and TIMP-2 of thyroid medullary carcinoma TT cells and related
      biological characteristics. METHODS: Protein expression of CD147, ANXA2, MMP-2
      and TIMP-2 was detected by immunocytochemistry.RNAi technology was used to
      identify the specific siRNA sequences and the optimal time point of effective
      inhibition of CD147 gene. The expression of ANXA2, MMP-2 and TIMP-2 at mRNA and
      protein levels was detected with RT-PCR and Western blot, respectively. MTT
      method was used to detect the proliferation of the TT cells, flow cytometry (FCM)
      to detect the cell cycle and apoptosis changes of TT cells and transwell chamber
      assays to document the influence of CD147 gene silencing on migration and
      invasion of the TT cells. RESULTS: The protein expression of CD147, ANXA2, MMP-2
      and TIMP-2 proteins was variable in the TT cells. Two siRNA sequences were
      identified to effectively silence CD147 gene in the TT cells, in which relative
      expression of MMP-2 was reduced at both mRNA and protein levels; although the
      expression of ANXA2 mRNA and protein did not change significantly. TIMP-2 protein
      expression markedly decreased in an absence of its mRNA expression. The
      proliferation of the TT cells was inhibited upon the CD147 gene silencing along
      with a significant increase of G(0)/G(1) phase cells and a decrease of G(2)/M
      phase cells.However, the proportion of the apoptotic cells in all experimental
      groups did not change. The number of the penetrating cells through the membrane
      filters did not show significant changes in all experimental groups in the
      Transwell chamber assays. CONCLUSIONS: Through RNAi technology, two CD147 siRNA
      sequences are identified and shown to effectively inhibit CD147 gene expression
      of the TT cells. CD147 gene silencing leads to growth inhibition of the TT cells
      and alteration of the cell cycle. However, silencing CD147 does not significantly
      affect the apoptosis, migration and invasion of the TT cells.

PMID- 24742571
TI  - [Histopathological changes in EV71-infected mouse model:a transmission electron
      microscopic study].
AB  - OBJECTIVE: To document ultrastructural changes of brain, spinal cord, skeletal
      muscle, jejunum and lung of EV71 infection mouse model, and to explore the
      myotropism and pathogenesis of EV71 in nervous system. METHODS: Ten-day-old
      suckling mice were infected with EV71 strain via the intraperitoneal route. Mice
      with paralysis were scarified on day 4 post infection and the brain, spinal cord,
      skeletal muscle, jejunum and lung were sampled for transmission electron
      microscopy and light microscopy. RESULTS: Lesions in brain were generally mild
      with inner chamber swelling in some of mitochondria. Myelin sheaths of medullated
      fibers were split with vacuolated changes. The Nissl bodies in anterior motor
      neurons disappeared along with mitochondria swelling, rough endoplasmic reticulum
      swelling and degranulation. Cytoplasm of anterior motor neurons showed cribriform
      appearance accompanied by neuronophagia. The bands of skeletal muscle in the
      infected group disappeared with degeneration and karyopyknosis in myocytes, in
      addition to mitochondrial swelling. Microvilli of epithelium in jejunum became
      loosely arranged along with formation of spiral medullary sheath structure and
      mitochondria swelling. Interstitial pneumonia was observed in lungs with type II
      pneumocyte proliferation and evacuation of the multilamellar bodies. CONCLUSIONS:
      EV71 infection causes severe myositis in the mouse model suggesting a strong
      myotropism of EV71 virus. The presence of lesions of various degrees in central
      nervous system and changes in anterior motor neurons may be associated with limb
      paralysis.

PMID- 24742572
TI  - [Primary dural MALT lymphoma: report of two cases].

PMID- 24742573
TI  - [Comparison of two different methods for EGFR gene mutation detection in non
      small cell lung cancer].

PMID- 24742574
TI  - [Primitive neuroectodermal tumor of kidney with multiple metastases : report of a
      case].

PMID- 24742575
TI  - [Primary leiomyosarcoma of adrenal gland: report of a case].

PMID- 24742576
TI  - [Renal carcinoma associated with Xp11.2 translocations/TFE3 gene fusions with
      lymph node metastasis diagnosed after an injury accident: report of a case].

PMID- 24742577
TI  - [Extranodal natural killer/T-cell lymphoma of soft tissue: report of a case].

PMID- 24742578
TI  - [Clinicopathologic features of ovarian clear cell carcinoma [correction of
      epithelial ovarian cancer] with yolk sac tumor component: report of a case].

PMID- 24742579
TI  - [Intravascular leiomyomatosis with extrarenal rhabdoid cells: report of a case].

PMID- 24742580
TI  - [Hyalinizing trabecular carcinoma of thyroid: report of a case].

PMID- 24742581
TI  - [Applications of genome wide association studies and whole genome sequencing in
      pancreatic cancer].

PMID- 24742582
TI  - [Research progress of role of cannabinoid receptor in fibrosis].

PMID- 24742584
TI  - Parathyroid carcinoma.
AB  - Parathyroid carcinoma is a rare form of endocrine malignancy accounting for only
      a small minority of cancer cases. Due to the rarity of this cancer, there are no
      generalized guidelines for its management; however, surgery remains to be the
      mainstay therapy. The purpose of this article is to review and summarize the
      available literature on parathyroid carcinoma, while discussing proposed staging
      systems and the role of available adjuvant therapies. 

PMID- 24742583
TI  - Sulforaphane counteracts aggressiveness of pancreatic cancer driven by
      dysregulated Cx43-mediated gap junctional intercellular communication.
AB  - The extreme aggressiveness of pancreatic ductal adenocarcinoma (PDA) has been
      associated with blocked gap junctional intercellular communication (GJIC) and the
      presence of cancer stem cells (CSCs). We examined whether disturbed GJIC is
      responsible for a CSC phenotype in established and primary cancer cells and
      patient tissue of PDA using interdisciplinary methods based in physiology, cell
      and molecular biology, histology and epigenetics. Flux of fluorescent dyes and
      gemcitabine through gap junctions (GJs) was intact in less aggressive cells but
      not in highly malignant cells with morphological dysfunctional GJs. Among several
      connexins, only Cx43 was expressed on the cell surface of less aggressive and
      GJIC-competent cells, whereas Cx43 surface expression was absent in highly
      malignant, E-cadherin-negative and GJIC-incompetent cells. The levels of total
      Cx43 protein and Cx43 phosphorylated at Ser368 and Ser279/282 were high in normal
      tissue but low to absent in malignant tissue. si-RNA-mediated inhibition of Cx43
      expression in GJIC-competent cells prevented GJIC and induced colony formation
      and the expression of stem cell-related factors. The bioactive substance
      sulforaphane enhanced Cx43 and E-cadherin levels, inhibited the CSC markers c-Met
      and CD133, improved the functional morphology of GJs and enhanced GJIC.
      Sulforaphane altered the phosphorylation of several kinases and their substrates
      and inhibition of GSK3, JNK and PKC prevented sulforaphane-induced CX43
      expression. The sulforaphane-mediated expression of Cx43 was not correlated with
      enhanced Cx43 RNA expression, acetylated histone binding and Cx43 promoter de
      methylation, suggesting that posttranslational phosphorylation is the dominant
      regulatory mechanism. Together, the absence of Cx43 prevents GJIC and enhances
      aggressiveness, whereas sulforaphane counteracts this process, and our findings
      highlight dietary co-treatment as a viable treatment option for PDA. 

PMID- 24742585
TI  - The highly-cited Electrocardiogram-related articles in science citation index
      expanded: characteristics and hotspots.
AB  - We used bibliometric analysis methodology in the expanded Science Citation Index
      to identify highly-cited electrocardiogram (ECG)-related articles with total
      citations (TC2012) exceeding 100 from the publication year to 2012. Web of
      Science search tools were used to identify the highly-cited articles. The aspects
      analyzed for highly cited publications included effect of time on citation
      analysis, journals and Web of Science categories, number of authors per
      publication, originating institutions and countries, total citation and total
      citation per year life cycles of articles (C2012) and research hotspots. Results
      showed that a total of 467 electrocardiogram-related publications were regarded
      as the highly-cited publications. TC2012 ranged from 101 to 2879, with 215 as the
      average number of citations. No highly-cited publications have emerged yet during
      the first two years of the present 2010 Decade. All 11 countries and institutions
      originating highly-cited ECG-related publications were developed countries, USA
      in 9 of them. Four subject categories were identified as hotspots by total
      citations TC2012 and C2012: atrial fibrillation, long QT syndrome, angina and
      myocardial infarction, and risk factor analysis and health evaluation. 

PMID- 24742586
TI  - Acute myocardial ischemia: cellular mechanisms underlying ST segment elevation.
AB  - The electrocardiogram (ECG) is an essential tool for the diagnosis of acute
      myocardial ischemia in the emergency department, as well as for that of an
      evolving acute myocardial infarction (AMI). Changes in the surface ECG in leads
      whose positive poles face the ischemic region are known to be related to injury
      currents flowing across the boundaries between the ischemic and the surrounding
      normal myocardium. Although experimental studies have also shown an endocardium
      to epicardium differential sensitivity to the effect of acute ischemia, the
      important contribution of this transmural heterogeneous response to the changes
      observed in the surface ECG is less appreciated by the clinical cardiologist.
      This review briefly discusses our current knowledge regarding the
      electrophysiology of the ischemic myocardium focusing primarily on the
      electrophysiologic changes underlying the ECG alterations observed at the onset
      of a transmural AMI. 

PMID- 24742588
TI  - Acute coronary syndrome management in older adults: guidelines, temporal changes
      and challenges.
AB  - Advancing age is a risk factor for the development of coronary artery disease and
      is an important indicator of outcome after acute coronary syndrome. As the number
      of older adults increases, the burden of cardiovascular disease is set to grow
      particularly as older adults remain disadvantaged in the delivery of acute
      cardiac care. This article reviews the temporal changes in the provision of
      guideline recommended therapies for the management of acute coronary syndrome,
      discusses reasons for age-dependent inequalities in care and the challenges
      facing clinicians. 

PMID- 24742587
TI  - The Home-based Older People's Exercise (HOPE) trial: a pilot randomised
      controlled trial of a home-based exercise intervention for older people with
      frailty.
AB  - BACKGROUND: frailty is a state of vulnerability to stressor events. There is
      uncertainty about the beneficial effects of exercise interventions for older
      people with frailty. The Home-based Older People's Exercise (HOPE) programme is a
      12-week-exercise intervention for older people with frailty designed to improve
      mobility and function. METHODS: we tested feasibility of the HOPE programme in a
      two arm, assessor blind pilot randomised controlled trial (RCT). Eligibility
      criteria included living at home and receiving case manager care, being
      housebound or attending day centres in Bradford, UK. Intervention participants
      received the HOPE programme; control participants received usual care. Objectives
      were to gather process, resource, management and scientific data to inform the
      design of a definitive trial. Primary outcome was mobility, measured using the
      timed-up-and-go test (TUGT). Secondary outcomes were activities of daily living,
      health-related quality of life and depression. Participants were stratified by
      the baseline TUGT score. Randomisation was by the University of Leeds Clinical
      Trials Research Unit. RESULTS: eighty-four participants were recruited. Forty
      five were randomised to intervention and 39 to control. Forty intervention
      participants and 30 control participants were included in the intention-to-treat
      analysis. There was a non-significant trend towards a clinically important
      improved outcome in the intervention group (mean adjusted between-group
      difference in the TUGT 28.6 s, 95% CI -8.5, 65.9 s). There were no differences in
      secondary outcomes. CONCLUSION: the HOPE trial has provided preliminary evidence
      that the deterioration in mobility experienced by older people with frailty may
      be reduced through a 12-week-exercise intervention. The pilot trial has provided
      the necessary data to design a future definitive RCT.Trial registration and date
      of first participant randomisation.Current Controlled Trials: International
      Standard Randomised Controlled Trial Number ISRCTN57066881. Date of trial
      registration 19/05/2010. Date of first participant randomisation 15/07/2010.

PMID- 24742589
TI  - The radiological excision of high risk and malignant lesions using the INTACT
      breast lesion excision system. A case series with an imaging follow up of at
      least 5 years.
AB  - PURPOSE: To evaluate the efficacy of a BLES procedure as a primary excisional
      biopsy rather than a surgical wide local excision for treatment of a high risk or
      a malignant lesion. METHODS: 41 patients underwent a BLES procedure in order to
      attempt to remove a small breast lesion using a 15 mm or 20 mm wand from August
      2007 to January 2009. The lesions were either proven on prior core biopsy to show
      high risk or malignant pathology or were considered to be indeterminate or
      suspicious on ultrasound or mammography. The pathology was reviewed to include
      the final status of lesion excision. If margin involvement was demonstrated then
      a formal surgical excision was subsequently recommended. Follow up mammography or
      ultrasound was performed annually in patients following the final pathological
      diagnosis. RESULTS: 9 patients had a primary diagnosis of atypia (columnar cell
      change with atypia or atypical ductal hyperplasia (ADH)), 23 patients had ductal
      carcinoma in situ (DCIS) and 9 had an invasive carcinoma (IC) at the original
      BLES pathology. Clear BLES margins of >1 mm were obtained in 3/9 atypia lesions,
      15/23 DCIS and 0/9 IC. 12/13 low grade DCIS were completely excised. Subsequent
      surgical margin excisions were undertaken in 20 patients. After at least 5 years
      of follow up (mean 66 months), 1 lesion had recurred on imaging. CONCLUSION: A
      BLES excision has potential as an alternative technique to traditional surgical
      wide local excision in the management of certain small breast lesions with high
      risk and low grade malignant potential.

PMID- 24742590
TI  - Does the ultrasound dissector improve parathyroid gland preservation during
      surgery?
AB  - BACKGROUND: The most common complication of thyroid surgery is
      hypoparathyroidism, usually temporary. Ischemic injury or parathyroid avulsion
      are the causes of surgical hypoparathyroidism. We assessed the value of an
      ultrasound scalpel, the Harmonic Focus((r)) (HF), could prevent surgical-related
      hypoparathyroidism. METHODS: Patients consecutively undergoing total
      thyroidectomy using the HF from November 2009 to February 2011 were recruited and
      their clinical characteristics, type of operation, histology, and postoperative
      calcium levels (normal range: 2.10-2.55 mMol/l) were recorded. The prevalence of
      transient and permanent hypocalcemia was calculated for benign vs. malignant
      diseases and compared with a control group of 147 patients treated surgically in
      2005 using manual technique. RESULTS: 139 patients treated by the same surgeon
      with a total thyroidectomy (41.7% for a malignant disease) were considered.
      Prevalence of transient hypoparathyroidism (THP) was 45.2% and of definitive
      hypoparathyroidism (DHP) 1.4%. None of the patients with malignancies were
      hypocalcemic at 1-year follow-up. In the control group THP was found in 51.7% of
      cases and DHP in 5.4% (p < 0.001). CONCLUSIONS: Use of the ultrasound scalpel
      improved the likelihood of the parathyroid glands preservation during thyroid
      surgery. Paradoxically, the HF appears to be more effective in treating malignant
      disease, i.e. when central node dissection is required.

PMID- 24742591
TI  - An anomalous case of an indirect orbital floor fracture.
AB  - Fractures of the orbital floor are common in facial trauma. Those that comprise
      only the orbital floor are called indirect fractures or pure internal orbital
      floor fractures. We present the case of an indirect fracture of the orbital floor
      after direct trauma to the back of the head caused by a bicycle accident. To the
      best of our knowledge this is the first time that this mechanism for such a
      fracture has been reported.

PMID- 24742592
TI  - The effect of sildenafil and udenafil on testicular damage following ischemia
      reperfusion injury in rats.
AB  - PURPOSE: Ischemia-reperfusion injury can cause testicular damage and
      phosphodiesterase inhibitors are reported to regulate antioxidant activity. We
      investigated the prevention of ipsilateral and contralateral testicular damage
      using 2 phosphodiesterase inhibitors after testicular detorsion in rats.
      MATERIALS AND METHODS: A total of 28 adult male rats were randomly divided into 4
      groups of 7 each, including group 1-sham operation, group 2-testicular torsion
      and detorsion, group 3- testicular torsion and detorsion with sildenafil
      administration before detorsion and group 4- testicular torsion and detorsion
      with udenafil administration before detorsion. Tissue levels of malondialdehyde,
      total sulfhydryl and nitrite were evaluated, and histopathological changes in the
      groups were examined. RESULTS: Compared to group 1 significantly increased tissue
      malondialdehyde (p = 0.001), significantly decreased total sulfhydryl (p = 0.038)
      and insignificantly increased nitrite were found in group 2. Compared to group 2
      malondialdehyde decreased significantly and total sulfhydryl increased
      significantly in groups 3 and 4. The decrease in nitrite was insignificant in the
      latter 2 groups. Histopathology revealed increased hemorrhage, congestion and
      edema in group 2 rats. The testicular injury score was lower in groups 3 and 4.
      In group 2 grades II to IV injury was detected while most specimens in treated
      groups showed grade II injury. CONCLUSIONS: This study indicates that
      intraperitoneal administration of sildenafil and udenafil efficiently suppresses
      radical production while decreasing histological changes after testicular
      ischemia-reperfusion injury.

PMID- 24742593
TI  - Regular transition zone biopsy during active surveillance for prostate cancer may
      improve detection of pathological progression.
AB  - PURPOSE: We investigated the frequency of cancer and pathological progression in
      transition zone biopsies in men undergoing multiple rebiopsies while on active
      surveillance. MATERIALS AND METHODS: Eligibility criteria of the active
      surveillance prostate cancer database (1997 to 2012) at our tertiary center
      includes prostate specific antigen 10 ng/ml or less, cT2 or less, no Gleason
      grade 4 or 5, 3 or fewer positive cores, no core with greater than 50%
      involvement, patient age 75 years or less and 1 or more biopsies after initial
      diagnostic biopsy. We excluded from analysis men with fewer than 10 cores at
      diagnostic biopsy and/or confirmatory biopsy greater than 24 months after
      diagnostic biopsy. Multiparametric magnetic resonance imaging was performed
      selectively to investigate incongruity between prostate specific antigen and
      biopsy findings. Pathological progression was defined by grade and/or volume
      (greater than 50% of core involved). Transition zone progression was subdivided
      into exclusively transition zone and combined transition zone (transition and
      peripheral zones). A multivariate Cox proportional hazards model was used to
      determine predictors of transition zone progression. RESULTS: A total of 392 men
      were considered in analysis. Median followup was 45.5 months. At each biopsy
      during active surveillance (confirmatory biopsy to biopsy 5+) there were
      transition zone positive cores in 18.6% to 26.7% of cases, all transition zone
      progression in 5.9% to 11.1% and exclusively transition zone progression in 2.7%
      to 6.7%. Volume related progression was noted more frequently than grade related
      progression (24 vs 9 cases). Predictors of only transition zone progression were
      the maximum percent in a single core (HR 1.99, 95% CI 1.30-3.04, p = 0.002) and
      cancer on magnetic resonance imaging (HR 3.19, 95% CI 1.23-8.27, p = 0.02).
      CONCLUSIONS: Across multiple active surveillance biopsies 2.7% to 6.7% of men had
      only transition zone progression. We recommend that transition zone biopsy be
      considered in all men at confirmatory biopsy. Positive magnetic resonance imaging
      findings or a high percent of core involvement may subsequently be useful to
      identify patients at risk.

PMID- 24742595
TI  - Management of urinary fistulas due to midurethral sling surgery.
AB  - PURPOSE: We report our experience with the diagnosis and treatment of women with
      urinary fistula after mid urethral sling surgery. MATERIALS AND METHODS: We
      retrospectively reviewed the records of patients with urinary fistula secondary
      to mid urethral sling surgery. Electronic medical records and billing records
      were searched. We analyzed sling type, presenting symptoms and interval from
      initial sling surgery to 1) symptom appearance, 2) fistula diagnosis and 3)
      fistula repair. Symptomatic outcomes were assessed by PGI-I. Surgical outcomes
      were based on history and examination. RESULTS: We identified 10 women with a
      mean age of 58 years (range 37 to 70). Mean interval from mid urethral sling
      surgery to symptom onset, diagnosis and fistula repair was 2, 16 and 18 months,
      respectively. Mean followup was 26 months (range 4 to 96). There were 1
      ureterovaginal, 1 enterovesical, 6 vesicovaginal and 7 urethrovaginal fistulas.
      Patients presented with stress urinary incontinence (70%), unaware incontinence
      (50%), overactive bladder (40%), pelvic pain (30%) and voiding symptoms (20%).
      Nine women underwent fistula repair and 1 underwent continent urinary diversion.
      A Martius flap was used in 6 of 9 patients, an omental flap and a bladder wall
      flap were used in 2 each, urethral reconstruction and ureterocolovesicostomy were
      performed in 1 each and 7 received an autologous pubovaginal sling. Seven
      patients (78%) underwent successful fistula repair. A successful symptomatic
      outcome was achieved in 5 of 7 women with stress urinary incontinence, 3 of 5
      with unaware incontinence, 3 of 4 with overactive bladder, 2 of 3 with pelvic
      pain and 2 of 2 with voiding symptoms. CONCLUSIONS: With careful attention to
      surgical principles and technique, including removal of as much of the adjacent
      mesh as possible, a successful outcome can be achieved in most patients with a
      fistula secondary to mid urethral sling surgery.

PMID- 24742597
TI  - Androgen dependent penile development and erection physiology-a molecular
      connection?

PMID- 24742598
TI  - Depression and neuroticism in patients with chronic hepatitis C: correlation with
      peripheral blood mononuclear cells activation.
AB  - BACKGROUND: Hepatitis C virus (HCV) infection is commonly associated with
      cognitive dysfunction and depression, which could be related to direct brain
      infection. Viral sequences and proteins were found in brain macrophage/microglia
      cells and these cells were reported to be activated. Since blood leukocytes cross
      blood-brain barrier, activation state of peripheral blood mononuclear cells
      (PBMC) could reflect the state of brain immune cells. OBJECTIVE: The aim of the
      study was to determine whether depression and neuroticism in chronic HCV
      infection correlates with the expression of key cytokines and chemokines in PBMC.
      DESIGN: We studied 24 HCV-positive patients undergoing treatment with interferon
      and ribavirin. Patients were tested for depression using Beck Depression
      Inventory (BDI) and Montgomery Asberg Depression Rating Scale (MADRS), while
      neuroticism was assessed by the Revised Eysenck Personality Inventory (N/EPO-R).
      Transcripts representing 28 various cytokines and chemokines were measured by
      real-time quantitative PCR in PBMC. RESULTS: Prior to therapy BDI and MADRS
      positively correlated with viral load while neuroticism correlated with IL-3, IL
      8 and M-CSF transcription levels. Six months after therapy there was positive
      correlation between depression and/or neuroticism scores and the levels of
      proinflammatory cytokines TNF-alpha and IL-12 transcripts, as well as IL-8, IL
      10, IL-16, MCP-1, MCP-2, MIP-1-alpha, MIP-1-beta, and TGF-beta, and IFN-beta
      transcripts. CONCLUSION: Activation of PBMC, as measured by the level of cytokine
      and chemokine transcripts, correlates with depression and neuroticism scores.
      These findings suggest a pivotal role of immune cells activation in depression
      and possibly neurocognitive dysfunction among chronic hepatitis C patients.

PMID- 24742599
TI  - Intrafamilial transmission of human cytomegalovirus (HCMV): long-term dynamics of
      epitope-specific antibody response in context of avidity maturation.
AB  - BACKGROUND: The role of a special early family formation (PEKiP), which is
      popular in Germany, as a potential origin of HCMV-transmission to seronegative
      mothers is not documented. OBJECTIVES: To describe the clinical courses, to
      identify the virological origin and to evaluate a new tool for diagnosis of a
      cascade of intrafamilial HCMV primary infections. STUDY DESIGN: This
      prospectively analyzed long-term course of HCMV primary infection leading to
      hospitalization of two family members, included the evaluation of different
      IgG/IgM/IgG avidity-assays with an epitope-specific recombinant immunoblot-assay.
      Additionally, neutralization (NT) assays using fibroblast-and epithelial-target
      cells were performed to correlate NT50 values to avidity maturation. HCMV
      gN/gO/gB-RFLP-genotyping and phylogenetic analyses were performed using urine
      viral isolates. RESULTS: The clinical courses of the sequentially occurring
      intrafamilial HCMV primary infections were unusual, leading to hospitalization.
      Long-term-serology of the mother revealed concordant results for an unimodal IgG
      course and a rapid decrease of IgM-indices from week 7 to week 21 p.i.
      Interestingly, the cut-off definitions for low and high avidity ranged
      discordantly from 15 to 25 weeks, and from 18 to 42 weeks p.i., respectively. A
      good correlation was found between the increase of fibroblast-adapted NT50 values
      and the appearance of high avidity using the epitope-specific immunoblot (>18
      weeks p.i.). RFLP-genotyping and sequencing could identify the index patient as
      member of PEKiP-meetings. CONCLUSIONS: PEKiP-meetings with naked babies may be an
      important source of horizontal HCMV-transmission to seronegative pregnant mothers
      in Germany. Using epitope-specific immunoblots, persisting HCMVp150-IgM
      reactivities and good concordance between high IgG-avidity and increase of
      fibroblast adapted neutralization capacity were found.

PMID- 24742600
TI  - Challenges in molecular epidemiology of hepatitis C virus.

PMID- 24742601
TI  - Training of public health personnel in handling CBRN emergencies: a table-top
      exercise card concept.
AB  - There is a large concern in the society today about the threat posed from
      releases of chemical, biological, radiological or nuclear (CBRN) materials,
      whether accidental or malicious. A rapid and adapted response to a CBRN incident
      combined with a thorough public communication is believed to decrease the
      detrimental impacts on health and to reduce the psychosocial effects. To
      facilitate CBRN exercises, which often can be regarded by non-specialists as
      rather complicated, a tool in the form of a set of Exercise cards for CBRN
      emergency response table-top exercises has been developed. The exercise tool is a
      generic tool intended for an exercise director and consists of a set of adaptable
      scenarios with supporting instructions and questions that deal with preparedness,
      acute response and mitigation efforts. The exercise tool was tested in three
      different settings with positive results and has been assessed to be a cost
      efficient means to train and test public health response to CBRN incidents. 

PMID- 24742602
TI  - Enhanced intracellular survival and epithelial cell adherence abilities of
      Burkholderia pseudomallei morphotypes are dependent on differential expression of
      virulence-associated proteins during mid-logarithmic growth phase.
AB  - Colony morphology variation is a characteristic of Burkholderia pseudomallei
      primary clinical isolates, associated with variations in expression of virulence
      factors. Here, we performed comparative investigations on adhesion, invasion,
      plaque-forming abilities and protein profiles of B. pseudomallei wild-type (WT)
      and a small colony variant (SCV). The percentage of SCV adherence to A549 cells
      was significantly higher (2.73%) than WT (1.91%). In contrast, WT was
      significantly more efficient (0.63%) than SCV (0.31%) in invasiveness and in
      inducing cellular damage. Using 2-DE and MALDI TOF/TOF, 263 and 258 protein spots
      were detected in WT and SCV, respectively. Comparatively, 49 proteins were
      differentially expressed in SCV when compared with WT. Of these, 31 proteins were
      up-regulated, namely, nucleoside diphosphate kinase (Ndk), phosphoglycerate
      kinase (Pgk), thioredoxin (TrxA), putative ferritin DPS-family DNA-binding
      protein (DPS) and oxidoreductase (AhpC) that are known to be involved in
      adhesion, intracellular survival and persistence. However, among the 18 down
      regulated proteins, enolase (Eno), elongation factor (EF-Tu) and universal stress
      related proteins were associated with invasion and virulence. Differences
      observed in these protein profiles provide ample clues to their association with
      the morphotypic and phenotypic characteristics of colony variants, providing
      additional insights into the potential association of B. pseudomallei colony
      morphotypes with disease pathogenesis. BIOLOGICAL SIGNIFICANCE: Comparative
      analyses were performed on the ability of wild-type and small colony variant of
      B. pseudomallei to adhere, invade and form plaques on human epithelial cells. In
      addition, proteomic analysis of these different colony morphotypes was also
      carried out. This research provides insights into the virulence and pathogenesis
      attributes of B. pseudomallei and contributes to better understand the
      pathogenesis of melioidosis.

PMID- 24742603
TI  - Impact of polypill difficult to demonstrate from varied studies, say Cochrane
      reviewers.

PMID- 24742605
TI  - The Polycomb group protein RING1B is overexpressed in ductal breast carcinoma and
      is required to sustain FAK steady state levels in breast cancer epithelial cells.
AB  - In early stages of metastasis malignant cells must acquire phenotypic changes to
      enhance their migratory behavior and their ability to breach the matrix
      surrounding tumors and blood vessel walls. Epigenetic regulation of gene
      expression allows the acquisition of these features that, once tumoral cells have
      escape from the primary tumor, can be reverted. Here we report that the
      expression of the Polycomb epigenetic repressor Ring1B is enhanced in tumoral
      cells that invade the stroma in human ductal breast carcinoma and its expression
      is coincident with that of Fak in these tumors. Ring1B knockdown in breast cancer
      cell lines revealed that Ring1B is required to sustain Fak expression in basal
      conditions as well as in Tgfbeta-treated cells. Functionally, endogenous Ring1B
      is required for cell migration and invasion in vitro and for in vivo invasion of
      the mammary fat pad by tumoral cells. Finally we identify p63 as a target of
      Ring1B to regulate Fak expression: Ring1B depletion results in enhanced p63
      expression, which in turns represses Fak expression. Importantly, Fak
      downregulation upon Ring1B depletion is dependent on p63 expression. Our findings
      provide new insights in the biology of the breast carcinoma and open new avenues
      for breast cancer prognosis and therapy. 

PMID- 24742607
TI  - Dental Practice Scenario in a Government Homeopathic Hospital in West Bengal,
      India.
AB  - This pilot investigation initiated a research-targeted systematic dental
      homeopathy data collection in the dental outpatient section in a government
      homeopathic hospital in West Bengal, India. One conventionally trained dentist
      and 3 homeopathic doctors collected data from 949 appointments of 411 patients
      over 3 months. A specifically designed Excel spreadsheet enabled recording of
      consecutive dental appointments that was subjected to data synthesis and analysis
      in the end. A total of 87.3% conditions were chronic, and chronic periodontitis
      was most frequent (27.5%). Positive outcome was observed in 72.3% appointments.
      Strongly positive outcomes (scores of +2 or +3) were achieved most notably in
      toothache (84.6%). Single medicines were prescribed in 83.5% encounters, and
      mostly in tincture form (29.9%). Arnica montana constituted of 17.8%
      prescriptions. Considerable insight was gained into the homeopathic dental
      practice scenario in West Bengal, India. Positive findings suggest that dental
      homeopathy is a promising area for research in near future.

PMID- 24742606
TI  - Pathologic complete response after neoadjuvant chemotherapy in HER2
      overexpressing breast cancer according to hormonal receptor status.
AB  - OBJECTIVE: For patients with HER2-positive breast cancer, the prognostic impact
      of pathologic complete response (pCR) after neoadjuvant chemotherapy (NAC) is
      unclear when stratified by hormonal receptor (HR) status; however, the impact of
      pCR on survival when stratified by hormonal receptor (HR) status is uncertain.
      PATIENTS AND METHODS: This multicenter retrospective study investigated the
      predictors of pCR and its prognostic value in Japanese patients 366 HER2-positive
      breast cancer who received NAC. pCR was defined as no invasive residual tumor in
      the breast or axilla. RESULTS: Median follow-up was 55 months. Multivariate
      analysis revealed that HR status (OR, 0.37; p < 0.001) was one of the independent
      predictors of pCR. Five-year recurrence-free survival was higher in HR-negative
      patients with pCR (93%) than in those without pCR (68%), and pCR was
      independently prognostic (hazard ratio, 0.32; p = 0.005). However, 5-year
      recurrence-free survival was not different between HR-positive patients with pCR
      (94%) and those without pCR (84%), and pCR was not significantly prognostic
      (hazard ratio, 0.53; p = 0.39). In addition, 5-year overall survivals were high
      and similar (97% in pCR, 94% in non-pCR). Among 204 patients treated with
      neoadjuvant trastuzumab, pCR was not significantly prognostic in the HR-positive
      group (hazard ratio, 0.63; p = 0.56). CONCLUSION: Our study suggested that the
      HER2-positive HR-positive patients had a good prognosis despite the lower
      achievement rate of pCR, whose prognostic impact was smaller than that in the
      HER2-positive HR-negative patients. The treatment strategy for HER2-positive
      breast cancer can be stratified by HR status.

PMID- 24742608
TI  - Spirulina maxima Protects Liver From Isoniazid and Rifampicin Drug Toxicity.
AB  - Hepatotoxicity associated with isoniazid and rifampicin is one of the major
      impediments in antituberculosis therapy. The present study explored the
      prophylactic and therapeutic efficacies of Spirulina maxima in isoniazid and
      rifampicin induced hepatic damage in a rat model. Hepatic damage induced in
      Wistar rats by isoniazid and rifampicin resulted in significant alterations in
      biomarkers of liver function, namely, bilirubin, aspartate transaminase, alanine
      transaminase, alkaline phosphatase, and oxidative stress markers such as
      superoxide dismutase, catalase, glutathione, and thiobarbituric acid reactive
      substances. Co-administration of Spirulina maxima along with antituberculosis
      drugs protected liver from hepatotoxicity due to isoniazid and rifampicin.
      Administration of Spirulina maxima consecutively for 2 weeks to hepatodamaged
      animals resulted in restoration of hepatic function as evident from normalization
      of serum markers of liver function. Thus, the present study revealed remarkable
      prophylactic and therapeutic potential of Spirulina maxima. Co-administration of
      Spirulina maxima and antituberculosis drugs is advantageous as it provides extra
      nutritional benefit.

PMID- 24742609
TI  - The Effect of Extract/Fractions of Caralluma tuberculata on Blood Glucose Levels
      and Body Weight in Alloxan-Induced Diabetic Rabbits.
AB  - Caralluma tuberculata is a cooked food item in Pakistan especially for diabetics.
      The current study was designed to explore the antidiabetic potential of
      extract/fractions of Caralluma tuberculata in alloxan-induced diabetic rabbits
      and its effect on body weight. The crude extract of the plant provoked 24% and
      44% antidiabetic action at 25 and 50 mg/kg OP, respectively, after the 24th day
      of treatment, which was strongly supported by a positive effect on the body
      weight of animals. On fractionation, pretreatment of the ethyl acetate fraction
      demonstrated most dominant (25.17% and 34.83%) antidiabetic activity followed by
      n-hexane (19.33% and 32.76%) and aqueous fractions (16.44% and 22.36%) at 25 and
      50 mg/kg OP, respectively, after the 24th day of treatment. The corresponding
      effect on blood glucose was also observed on body weight of diabetic rabbits. In
      sum, extract/fractions of the plant showed marked antidiabetic action and thus a
      provided scientific foundation to the use of the plant as an antidiabetic.

PMID- 24742610
TI  - Cavitary pulmonary disease in a patient treated with natalizumab.

PMID- 24742611
TI  - Peripheral neuropathy during infliximab therapy for rheumatoid arthritis.

PMID- 24742612
TI  - [ALS treatment: state of the art in 2014 and perspectives].
AB  - Progresses in the multidisciplinary care, particularly in the nutritional and
      respiratory management, allowed improving the quality of life and survival of ALS
      patients. Non-invasive ventilation is initially performed overnight but with the
      progression of diaphragmatic weakness, a continuous ventilatory support is often
      needed. Advances directives regarding end-of-life issues are important to respect
      patient's wishes regarding the choice of invasive ventilation with tracheostomy.
      Riluzole is the only neuroprotective drug that has demonstrated a significant but
      modest effect on survival and is well tolerated The failure of therapeutic trials
      may be partly related to the heterogeneity of the disease. Recent progress in the
      genetic of ALS may lead to new therapeutic strategies. Results of therapeutic
      trials with drugs or nutritional intervention are expected in 2014. 

PMID- 24742613
TI  - [Psychiatric symptoms during pregnancy: don't forget metabolic diseases!].

PMID- 24742614
TI  - [Talalgia one month after recovery jog: Think of stress fracture].

PMID- 24742615
TI  - [Polyuria-polydipsia syndrome associated with bone pains].

PMID- 24742616
TI  - [Perioperative management of new oral anticoagulants].
AB  - New oral anticoagulants do represent a major step forward as compared to low
      molecular weight heparins and vitamin K antagonists. Several issues deserve
      attention regarding their perioperative management. Three (and very soon four or
      five) active molecules are available on the market, adding to the major intra-
      and inter-individual variability, to the high number of drug-drug interactions,
      and to the interferences of renal function and many other parameters. New tests
      are available including the diluted thrombin time for dabigatran and a specific
      anti-Xa test for rivaroxaban and apixaban. No antidote is approved yet. Scheduled
      surgery: the safest suggestion is to mimic the perioperative management of
      vitamin K antagonist, with a 5-day interruption and low molecular weight heparin
      bridging whenever necessary. Emergency procedures: several suggestions issued
      from the Groupe d'Interet en Hemostase Peri-operatoire are proposed.

PMID- 24742617
TI  - Upper gastrointestinal obstruction due to trichobezoar.

PMID- 24742618
TI  - Functional Connectivity Bias in the Prefrontal Cortex of Psychopaths.
AB  - BACKGROUND: Psychopathy is characterized by a distinctive interpersonal style
      that combines callous-unemotional traits with inflexible and antisocial behavior.
      Traditional emotion-based perspectives link emotional impairment mostly to
      alterations in amygdala-ventromedial frontal circuits. However, these models
      alone cannot explain why individuals with psychopathy can regularly benefit from
      emotional information when placed on their focus of attention and why they are
      more resistant to interference from nonaffective contextual cues. The present
      study aimed to identify abnormal or distinctive functional links between and
      within emotional and cognitive brain systems in the psychopathic brain to
      characterize further the neural bases of psychopathy. METHODS: High-resolution
      anatomic magnetic resonance imaging with a functional sequence acquired in the
      resting state was used to assess 22 subjects with psychopathy and 22 control
      subjects. Anatomic and functional connectivity alterations were investigated
      first using a whole-brain analysis. Brain regions showing overlapping anatomic
      and functional changes were examined further using seed-based functional
      connectivity mapping. RESULTS: Subjects with psychopathy showed gray matter
      reduction involving prefrontal cortex, paralimbic, and limbic structures.
      Anatomic changes overlapped with areas showing increased degree of functional
      connectivity at the medial-dorsal frontal cortex. Subsequent functional seed
      based connectivity mapping revealed a pattern of reduced functional connectivity
      of prefrontal areas with limbic-paralimbic structures and enhanced connectivity
      within the dorsal frontal lobe in subjects with psychopathy. CONCLUSIONS: Our
      results suggest that a weakened link between emotional and cognitive domains in
      the psychopathic brain may combine with enhanced functional connections within
      frontal executive areas. The identified functional alterations are discussed in
      the context of potential contributors to the inflexible behavior displayed by
      individuals with psychopathy.

PMID- 24742619
TI  - Presynaptic D2 dopamine receptors control long-term depression expression and
      memory processes in the temporal hippocampus.
AB  - BACKGROUND: Dysfunctional mesocorticolimbic dopamine signaling has been linked to
      alterations in motor and reward-based functions associated with psychiatric
      disorders. Converging evidence from patients with psychiatric disorders and use
      of antipsychotics suggests that imbalance of dopamine signaling deeply alters
      hippocampal functions. However, given the lack of full characterization of a
      functional mesohippocampal pathway, the precise role of dopamine transmission in
      memory deficits associated with these disorders and their dedicated therapies is
      unknown. In particular, the positive outcome of antipsychotic treatments,
      commonly antagonizing D2 dopamine receptors (D2Rs), on cognitive deficits and
      memory impairments remains questionable. METHODS: Following pharmacologic and
      genetic manipulation of dopamine transmission, we performed anatomic,
      neurochemical, electrophysiologic, and behavioral investigations to uncover the
      role of D2Rs in hippocampal-dependent plasticity and learning. Naive mice (n = 4
      21) were used in the different procedures. RESULTS: Dopamine modulated both long
      term potentiation and long-term depression in the temporal hippocampus as well as
      spatial and recognition learning and memory in mice through D2Rs. Although
      genetic deletion or pharmacologic blockade of D2Rs led to the loss of long-term
      potentiation expression, the specific genetic removal of presynaptic D2Rs
      impaired long-term depression and performances on spatial memory tasks.
      CONCLUSIONS: Presynaptic D2Rs in dopamine fibers of the temporal hippocampus
      tightly modulate long-term depression expression and play a major role in the
      regulation of hippocampal learning and memory. This direct role of
      mesohippocampal dopamine input as uncovered here adds a new dimension to dopamine
      involvement in the physiology underlying deficits associated with
      neuropsychiatric disorders.

PMID- 24742620
TI  - Development of impulse control circuitry in children of alcoholics.
AB  - BACKGROUND: Difficulty with impulse control is heightened in children with a
      family history of alcohol use disorders and is a risk factor for later substance
      problems. Cross-sectional functional magnetic resonance imaging studies have
      shown altered impulse control processing in adolescents with a positive family
      history, yet developmental trajectories have yet to be examined. METHODS:
      Longitudinal functional magnetic resonance imaging was conducted in children of
      alcoholic families (family history positive [FH+]; n = 43) and children of
      control families (family history negative [FH-]; n = 30) starting at ages 7-12
      years. Participants performed a go/no-go task during functional magnetic
      resonance imaging at intervals of 1-2 years, with two to four scans performed per
      subject. We implemented a repeated-measures linear model fit across all subjects
      to conduct a whole-brain search for developmental differences between groups.
      RESULTS: Performance improved with age in both groups, and there were no
      performance differences between groups. Significant between-group differences in
      linear age-related activation changes were found in the right caudate, middle
      cingulate, and middle frontal gyrus. Post hoc analyses revealed significant
      activation decreases with age in the caudate and middle frontal gyrus for FH-
      subjects and a significant increase with age in middle cingulate activation for
      FH+ subjects. Group differences were evident at age 7-12 years, even in alcohol-
      and drug-naive participants, with FH+ subjects showing significantly blunted
      activation at baseline compared with FH- subjects. CONCLUSIONS: Differences in
      response inhibition circuitry are visible in FH+ individuals during childhood;
      these differences continue into adolescence, displaying trajectories that are
      inconsistent with development of normal response inhibition. These patterns
      precede problem drinking and may be a contributing factor for subsequent
      substance use problems.

PMID- 24742621
TI  - Calcineurin downregulation in the amygdala is sufficient to induce anxiety-like
      and depression-like behaviors in C57BL/6J male mice.
AB  - BACKGROUND: The calcium-dependent phosphatase calcineurin is highly expressed in
      the amygdala, a brain area important for behaviors related to mood disorders and
      anxiety. Organ transplant patients are administered the calcineurin inhibitor
      cyclosporine A (CsA) chronically and demonstrate an increased incidence of
      anxiety and mood disorders. It is therefore important to determine whether
      chronic blockade of calcineurin may contribute to symptoms of anxiety and
      depression in these patients. METHODS: Pharmacological (CSA) and viral-mediated
      gene transfer (adeno-associated viral expression of short hairpin RNA [shRNA])
      approaches were used to inhibit calcineurin activity systemically or selectively
      in the amygdala of the mouse brain to determine the role of calcineurin in
      behaviors related to anxiety and depression. RESULTS: Systemic inhibition of
      calcineurin activity with CsA or local downregulation of calcineurin levels in
      the amygdala using adeno-associated viral-delivered shRNAs targeting calcineurin
      B increased measures of anxiety-like behavior in the elevated plus maze, the
      light/dark box, and the open field test. A decrease in locomotor activity was
      also observed in mice treated systemically with CsA. In the forced swim model of
      depression-like behavior, both systemic CsA treatment and shRNA-mediated
      calcineurin blockade in the amygdala significantly increased immobility.
      CONCLUSIONS: Taken together, these data demonstrate that decreasing calcineurin
      activity in the amygdala increases anxiety-like behaviors and to some extent
      depression-like behaviors. These studies suggest that chronic administration of
      CsA to organ transplant patients could have significant effects on anxiety and
      mood and this should be recognized as a potential clinical consequence of
      treatment to prevent transplant rejection.

PMID- 24742622
TI  - Oridonin inhibits hepatic stellate cell proliferation and fibrogenesis.
AB  - BACKGROUND: Liver fibrosis is a common response to liver injury and, in severe
      cases, leads to cirrhosis. The hepatic stellate cells (HSCs) become activated
      after liver injury and play a significant role in fibrogenesis. The activated HSC
      is characterized by increased proliferation, overexpression of alpha smooth
      muscle actin, and excessive production of extracellular matrix (ECM) proteins.
      Oridonin, a naturally occurring diterpenoid, has been shown to induce apoptosis
      in liver and gastric cancer cells. However, its effects on the HSC are unknown.
      METHODS: We tested the effects of oridonin on the activated human and rat HSC
      lines LX-2 and HSC-T6, and the human hepatocyte cell line C3A. Transforming
      growth factor beta1 (TGF-beta1) was used to stimulate LX-2 cells. RESULTS:
      Oridonin significantly inhibited LX-2 and HSC-T6 proliferation. In contrast,
      oridonin had no antiproliferative effect on C3A cells at our tested range.
      Oridonin induced apoptosis and S-phase arrest in LX-2 cells. These findings were
      associated with an increase in p53, p21, p16, and cleaved Poly (ADP-ribose)
      Polymerase (PARP), and with a decrease in Cyclin-dependent kinase 4 (Cdk4).
      Oridonin markedly decreased expression of alpha smooth muscle actin and ECM
      protein type I collagen and fibronectin, blocked TGF-beta1-induced Smad2/3
      phosphorylation and type I collagen expression. CONCLUSIONS: Oridonin induces
      apoptosis and cell cycle arrest involving the p53-p21 pathway in HSC and appears
      to be nontoxic to hepatocytes. In addition, oridonin suppressed endogenous and
      TGF-beta1-induced ECM proteins. Thus, oridonin may act as a novel agent to
      prevent hepatic fibrosis.

PMID- 24742623
TI  - Novel functional role of heat shock protein 90 in protein kinase C-mediated
      ischemic postconditioning.
AB  - BACKGROUND: Previous studies have shown that heat shock protein 90 (HSP90) plays
      a vital role in ischemic preconditioning. The present study was designed to
      explore whether HSP90 might be responsible for cardioprotection in ischemic
      postconditioning (PostC). MATERIALS AND METHODS: Rat hearts underwent 30 min of
      regional ischemia and 2 h of reperfusion in situ, and PostC was effected with
      three cycles of 30-s reperfusion and 30-s coronary artery occlusion at the end of
      ischemia. Ninety rats were randomized into five groups: sham; ischemia
      reperfusion (I/R); PostC; 1 mg/kg HSP90 inhibitor geldanamycin (GA) plus PostC
      (PostC + GA1); and 5 mg/kg GA plus PostC (PostC + GA5). The GA was administered
      10 min before reperfusion. RESULTS: Compared with the I/R group, the PostC group
      exhibited lower infarct size (46.7 +/- 3.0% versus 27.4 +/- 4.0%, respectively),
      release of lactate dehydrogenase and creatine kinase-MB (2252.6 +/- 350.8 versus
      1713.7 +/- 202.4 IU/L, 2804.3 +/- 315.7 versus 1846.2 +/- 238.0 IU/L,
      respectively), cardiomyocyte apoptosis (48.4 +/- 5.6% versus 27.6 +/- 3.8%,
      respectively), and mitochondrial damage. These beneficial effects were
      accompanied by an increase in mitochondrial Bcl-2 levels and a decrease in Bax
      levels. In addition, mitochondrial protein kinase Cepsilon (PKCepsilon) was
      relatively low in the I/R group but significantly higher in the PostC group,
      whereas cytosolic PKCepsilon was relatively high in the I/R group but
      significantly lower in the PostC group, suggesting the translocation of
      PKCepsilon from cytosol to mitochondria during PostC. However, blocking HSP90
      function with GA inhibited the protection of PostC and PKCepsilon mitochondrial
      translocation. CONCLUSIONS: HSP90 is critical in PostC-induced cardioprotection,
      and its activity might be linked to mitochondrial targeting of PKCepsilon, the
      activation of which results in upregulation of its target gene, Bcl-2, and the
      inhibition of proapoptotic Bax in mitochondria.

PMID- 24742624
TI  - The impact of pregnancy on surgical Crohn disease: an analysis of the Nationwide
      Inpatient Sample.
AB  - BACKGROUND: The impact of pregnancy on the course of Crohn disease is largely
      unknown. Retrospective surveys have suggested a variable effect, but there are
      limited population-based clinical data. We hypothesized pregnant women with Crohn
      disease will have similar rates of surgical disease as a nonpregnant Crohn
      disease cohort. MATERIAL AND METHODS: International Classification of Diseases,
      Ninth Revision, Clinical Modification codes were used to identify female Crohn
      patients from all patients admitted using the Nationwide Inpatient Sample (1998
      2009). Women were stratified as either pregnant or nonpregnant. We defined Crohn
      related surgical disease as peritonitis, gastrointestinal hemorrhage, intra
      abdominal abscess, toxic colitis, anorectal suppuration, intestinal-intestinal
      fistulas, intestinal-genitourinary fistulas, obstruction and/or stricture, or
      perforation (excluding appendicitis). RESULTS: Of the 92,335 women admitted with
      a primary Crohn-related diagnosis, 265 (0.3%) were pregnant. Pregnant patients
      were younger (29 versus 44 y; P<0.001) and had lower rates of tobacco use (6%
      versus 13%; P<0.001). Pregnant women with Crohn disease had higher rates of
      intestinal-genitourinary fistulas (23.4% versus 3.0%; P<0.001), anorectal
      suppuration (21.1% versus 4.1%; P<0.001), and overall surgical disease (59.6%
      versus 39.2%; P<0.001). On multivariate logistic regression analysis controlling
      for malnutrition, smoking, age, and prednisone use, pregnancy was independently
      associated with higher rates of anorectal suppuration (odds ratio [OR], 5.2; 95%
      confidence interval [CI], 3.8-7.0; P<0.001), intestinal-genitourinary fistulas
      (OR, 10.4; 95% CI, 7.8-13.8; P<0.001), and overall surgical disease (OR, 2.9; 95%
      CI, 2.3-3.7; P<0.001). CONCLUSIONS: Pregnancy in women with Crohn disease is a
      significant risk factor for Crohn-related surgical disease, in particular,
      anorectal suppuration and intestinal-genitourinary fistulas.

PMID- 24742625
TI  - [Overweight and obesity prevalence estimates in a population from Zaragoza by
      using different growth references].
AB  - OBJECTIVES: To investigate the prevalence of overweight and obesity among our
      pediatric population and observe whether the use of different growth references
      for classification produce significant differences. MATERIAL AND METHODS: A total
      of 35824 boys and girls aged between 2 and 14 years were included. Body mass
      index (BMI) was used to calculate the prevalence of overweight-obesity by age and
      sex. Prevalence was obtained by using a set of national references (Hernandez's
      standards) and the references of World Health Organization (WHO standards).
      Prevalences were compared for each age and sex subset, as well as with the
      percentage of patients who had an overweight-obesity diagnosis in the clinical
      record. RESULTS: The overall prevalence of overweight-obesity among children aged
      2 to 14 years was 17.0% (95% CI; 16.1%-18.0%) according to the Hernandez
      standards vs 30.8% (95% CI; 29.9%-31.7%) according to WHO standards (10.1% vs
      12.2% obese, and 6.9% vs 18.6% overweight). It was significantly higher in boys,
      by both standards, due to the higher prevalence of obesity. By using the
      Hernandez standards the prevalence was significantly lower than by using WHO
      standards for all ages and for both sexes. A low percentage of patients were
      found to have an obesity-overweight diagnosis in the clinical record (from 3% to
      22% at the ages of 2 and 14 years, respectively). CONCLUSIONS: The prevalence of
      overweight-obesity in our population is high, especially among boys. Using
      Hernandez standards leads to an under-estimation of the problem, especially
      because it detects less overweight patients, thus we recommend using the WHO
      standards in our daily practice. The low number of overweight-obesity diagnoses
      in the clinical records might reflect that there is little awareness of the
      problem by the professionals.

PMID- 24742626
TI  - Decapping Scavenger (DcpS) enzyme: advances in its structure, activity and roles
      in the cap-dependent mRNA metabolism.
AB  - Decapping Scavenger (DcpS) enzyme rids eukaryotic cells of short mRNA fragments
      containing the 5' mRNA cap structure, which appear in the 3'->5' mRNA decay
      pathway, following deadenylation and exosome-mediated turnover. The unique
      structural properties of the cap, which consists of 7-methylguanosine attached to
      the first transcribed nucleoside by a triphosphate chain (m(7)GpppN), guarantee
      its resistance to non-specific exonucleases. DcpS enzymes are dimers belonging to
      the Histidine Triad (HIT) superfamily of pyrophosphatases. The specific
      hydrolysis of m(7)GpppN by DcpS yields m(7)GMP and NDP. By precluding inhibition
      of other cap-binding proteins by short m(7)GpppN-containing mRNA fragments, DcpS
      plays an important role in the cap-dependent mRNA metabolism. Over the past
      decade, lots of new structural, biochemical and biophysical data on DcpS has
      accumulated. We attempt to integrate these results, referring to DcpS enzymes
      from different species. Such a synergistic characteristic of the DcpS structure
      and activity might be useful for better understanding of the DcpS catalytic
      mechanism, its regulatory role in gene expression, as well as for designing DcpS
      inhibitors of potential therapeutic application, e.g. in spinal muscular atrophy.

PMID- 24742627
TI  - Extra-prostatic transgene-associated neoplastic lesions in transgenic
      adenocarcinoma of the mouse prostate (TRAMP) mice.
AB  - Male transgenic adenocarcinoma of the mouse prostate (TRAMP) mice are frequently
      used in prostate cancer research because their prostates consistently develop a
      series of preneoplastic and neoplastic lesions. Disease progression in TRAMP
      mouse prostates culminates in metastatic, poorly differentiated carcinomas with
      neuroendocrine features. The androgen dependence of the rat probasin promoter
      largely limits transgene expression to the prostatic epithelium. However, extra
      prostatic transgene-positive lesions have been described in TRAMP mice, including
      renal tubuloacinar carcinomas, neuroendocrine carcinomas of the urethra, and
      phyllodes-like tumors of the seminal vesicle. Here, we describe the histologic
      and immunohistochemical features of 2 novel extra-prostatic lesions in TRAMP
      mice: primary anaplastic tumors of uncertain cell origin in the midbrain and
      poorly differentiated adenocarcinomas of the submandibular salivary gland. These
      newly characterized tumors apparently result from transgene expression in extra
      prostatic locations rather than representing metastatic prostate neoplasms
      because lesions were identified in both male and female mice and in male TRAMP
      mice without histologically apparent prostate tumors. In this article, we also
      calculate the incidences of the urethral carcinomas and renal tubuloacinar
      carcinomas, further elucidate the biological behavior of the urethral carcinomas,
      and demonstrate the critical importance of complete necropsies even when
      evaluating presumably well characterized phenotypes in genetically engineered
      mice. 

PMID- 24742628
TI  - Myocardial steatosis and necrosis in atria and ventricles of rats given pyruvate
      dehydrogenase kinase inhibitors.
AB  - Pharmaceutical therapies for non-insulin-dependent diabetes mellitus (NIDDM)
      include plasma glucose lowering by enhancing glucose utilization. The
      mitochondrial pyruvate dehydrogenase (PDH) complex is important in controlling
      the balance between glucose and fatty acid substrate oxidation. Administration of
      pyruvate dehydrogenase kinase inhibitors (PDHKIs) to rats effectively lowers
      plasma glucose but results in myocardial steatosis that in some instances is
      associated primarily with atrial and to a lesser degree with ventricular
      pathology. Induction of myocardial steatosis is not dose-dependent, varies from
      minimal to moderate severity, and is either of multifocal or diffuse
      distribution. Ventricular histopathology was restricted to few myocardial
      degenerative fibers, while that in the atrium/atria was of either acute or
      chronic appearance with the former showing myocardial degeneration/necrosis,
      acute myocarditis, edema, endothelial activation (rounding up), endocarditis, and
      thrombosis associated with moderate myocardial steatosis and the latter with
      myocardial loss, replacement fibrosis, and no apparent or minimal association
      with steatosis. The evidence from these evaluations indicate that excessive
      intramyocardial accumulation of lipid may be either primarily adverse or
      represents an indicator of other adversely affected cellular processes.

PMID- 24742629
TI  - Characterization of the low-temperature activity of Sulfolobus tokodaii glucose-1
      dehydrogenase mutants.
AB  - Thermophilic enzymes are potentially useful for industrial processes because they
      are generally more stable than are mesophilic or psychrophilic enzymes. However,
      a crucial drawback for their use in such processes is that most thermophilic
      enzymes are nearly inactive at moderate and low temperatures. We have previously
      proposed that modulation of the coenzyme-binding pocket of thermophilic
      dehydrogenases can produce mutated proteins with enhanced low-temperature
      activities. In the current study, we produced and characterized mutants of an
      NADP-dependent glucose-1-dehydrogenase from the hyperthermophile Sulfolobus
      tokodaii in which a predicted coenzyme-binding, non-polar residue was replaced by
      another non-polar residue. Detailed analyses of the kinetic properties of the
      wild-type enzyme and its mutants showed that one of the mutants (V254I) had
      improved kcat and kcat/Km values at both 25 degrees C and 80 degrees C.
      Temperature-induced unfolding experiments showed that the thermal stability of
      the mutant enzyme was comparable to that of the wild-type enzyme. Calculation of
      the energetic contribution of the V254I mutation for the dehydrogenase reaction
      revealed that the mutation destabilizes the enzyme-NADP(+)-glucose ternary
      complex and reduces the transition-state energy, thus enhancing catalysis. 

PMID- 24742630
TI  - Micropatterned culture of HepG2 spheroids using microwell chip with honeycomb
      patterned polymer film.
AB  - Microwell chip culture is a promising technique for the generation of homogenous
      spheroids. We investigated the relationship between the structure of the bottom
      surface of microwell chip and the properties of HepG2 spheroid. We developed a
      microwell chip, the bottom surface of which consisted of a honeycomb-patterned
      polymer film (honeycomb film) that had a regular porous structure (HF chip). The
      chip comprised 270 circular microwells; each microwell was 600 MUm in diameter
      and 600 MUm in depth. At the center of the honeycomb film, an area, 200 MUm in
      diameter, was modified with collagen to facilitate cell adhesion. With the
      exception of the collagen-coated area, the entire microwell was modified with
      polyethylene glycol to eliminate cell adhesion. HepG2 cells formed uniform
      spheroids when cultured in the microwells of HF chip. Furthermore, the cells
      passed through the porous structure of honeycomb film and formed spheroids at its
      opposite side. The spheroid growth of HepG2 cells cultured in HF chip was greater
      than that when the cells were culture in a microwell chip, the bottom surface of
      which was made of poly-methylmethacrylate (PMMA chip). The albumin secretion
      activity of HepG2 spheroids in HF chip was equal to that in PMMA chip. These
      results indicate that the microwell bottom with a porous structure enhances the
      cell growth and maintains well the spheroid function. Thus, HF chip is a
      promising platform for spheroid cell culture. 

PMID- 24742631
TI  - Antioxidant activities and phenolics of fermented Bletilla formosana with eight
      plant pathogen fungi.
AB  - The tubers of Bletilla formosana were fermented with eight plant pathogen fungi,
      respectively, and antioxidant activities and total phenolic content (TPC) of the
      crude extracts of fermented products and non-fermented products were
      investigated. The antioxidant activities were evaluated in three different test
      systems [DPPH, ABTS radical-scavenging activity, and ferric reducing-antioxidant
      power (FRAP)]. It was found that the extract of Helminthosporium maydis fermented
      B. formosana (FBF) possessed the highest TPC and exhibited a significant
      antioxidant activity compared with non-fermented product and other fermented
      products. Correlation analysis between antioxidant activities and TPC was also
      investigated. The good correlation between antioxidant activities and TPC
      revealed that the phenolic compounds might be the major contributors for the high
      antioxidant activities of the fermented B. formosana. Two phenolic compounds,
      curvularin and dehydrocurvularin, were isolated from H. maydis FBF, which had
      never been reported from plant of orchidaceae or H. maydis. Curvularin exhibited
      significant antioxidant activities, and was also present at a high concentration
      (0.373 mg/mg extract sample), implying an important role for the antioxidant
      activity of H. maydis FBF. This study suggested that proper fermentation
      processing could improve TPC and antioxidant activities of B. formosana. 

PMID- 24742632
TI  - Association between genes encoding components of the IL-4/IL-4 receptor pathway
      and dermatitis in children.
AB  - OBJECTIVE: To determine whether IL-4, IL-4Ralpha and STAT6 polymorphisms are
      associated with susceptibility to dermatitis in Egyptian children. METHODS: We
      genotyped three groups of children, consisting of 106 atopic dermatitis (AD)
      children, 95 non-AD children, and 100 of healthy controls, for IL-4 (-590 C/T), (
      33 C/T), IL-4Ralpha (I50V), (Q576R) and STAT6 (2964 G/A), (2892 C/T) gene
      polymorphisms using PCR-RFLP assay. Total serum IgE and serum IL-4 levels were
      detected by ELISA. RESULTS: There was a non-significant association of IL-4 -590
      C/T, -33 C/T polymorphisms in the children with non-AD or those with AD when
      compared with the controls. We identified a significant association between IL
      4Ralpha I50V, Q576R polymorphisms and dermatitis susceptibility in AD (p=0.002,
      <0.001 respectively), whereas no such association was observed in non-AD group
      (p=0.52, 0.99 respectively). A significant association between STAT6
      polymorphisms and both types of dermatitis was found. Patients who were carriers
      of IL4 -590C, IL-4Ralpha I50V G, STAT6 2964 A and STAT6 2892 T had an increased
      risk of AD [OR and 95% CI: 3.2 (2.5-4.2), p=0.005]. Furthermore, there was no
      relation between each polymorphism and serum IL-4 level (p>0.05 for each) while
      homozygosity for the risk alleles of IL-4, IL-4Ralpha and STAT6 SNPs were
      significantly associated with increased total IgE levels in all subjects.
      CONCLUSION: In Egyptian children, the IL-4Ralpha and the STAT6 polymorphism may
      play a role in susceptibility to AD. In addition, gene-gene interaction between
      the IL-4, the IL-4Ralpha and the STAT6 significantly increases an individual's
      susceptibility to AD.

PMID- 24742634
TI  - The role of depressive symptoms in the pathway of demographic and psychosocial
      risks to preterm birth and small for gestational age.
AB  - OBJECTIVE: depressive symptoms during pregnancy are associated with preterm birth
      (PTB) and small for gestational age (SGA). Depressive symptoms and PTB and SGA,
      however, share similar demographic and psychosocial risk factors. Therefore, we
      investigated whether depressive symptomatology is an independent risk factor, or
      a mediator in the pathway of demographic and psychosocial risks to PTB and SGA.
      DESIGN: multicentre follow-up study. PARTICIPANTS AND SETTING: pregnant women
      (n=1013) from midwifery practices, secondary hospitals and a tertiary hospital in
      three urban areas in the Netherlands. MEASUREMENTS: initial risk factors and
      depressive symptoms were assessed with the Mind2Care instrument, including
      Edinburgh Depression Scale (EDS) during early pregnancy. Pregnancy outcomes were
      extracted from medical records. A formal mediation analysis was conducted to
      investigate the role of depressive symptoms in the pathway to PTB and SGA.
      FINDINGS: a univariate association between depressive symptoms and PTB (OR:1.04;
      95% CI:1.00-1.08) was observed. After adjusting for the risk factors educational
      level and smoking in the mediation analysis, this association disappeared. One
      educational aspect remained associated: low education OR: 1.06; 95%-CI:1.02-1.10.
      KEY CONCLUSIONS: depressive symptomatology appeared no mediator in the pathway of
      demographic and psychosocial risks to PTB or SGA. The presumed association
      between depressive symptoms and PTB seems spurious and may be explained by
      demographic and psychosocial risk factors. IMPLICATIONS FOR PRACTICE: for the
      prevention of PTB and SGA, interventions directed at demographic and psychosocial
      risk factors are likely to be of primary concern for clinicians and public health
      initiatives. As depressive symptoms and PTB and SGA share similar risk factors,
      both will profit.

PMID- 24742635
TI  - Validation of the Edinburgh Postnatal Depression Scale as a screening tool for
      postpartum depression in a clinical sample in Hungary.
AB  - BACKGROUND: the purpose of the study was to assess the validity of the 10-item
      Edinburgh Postnatal Depression Scale (EPDS) in screening for postnatal depression
      (PND) in Hungary. METHODS: between July 2010 and March 2011, a sample of 266
      women attending a routine check-up at six weeks post partum completed the newly
      translated Hungarian version of the EPDS at the Department of Obstetrics and
      Gynecology, University of Szeged, Hungary, and underwent clinical assessments
      based on the Structured Clinical Interview for DSM-IV disorders (SCID-I).
      FINDINGS: eight (3.0%) of the mothers were diagnosed with major postnatal
      depression, and 36 (13.5%) with minor depression on the basis of the SCID.
      Internal consistency of the Hungarian version of the EPDS was satisfactory
      (Cronbach alpha coefficients >=0.727). The best cut-off for major depression was
      12/13, with a sensitivity of 100.0%, and a specificity of 97.7%. The area under
      the ROC curve was found significant for combined (major+minor) depression as well
      and at a cut-off of 7/8 indicated a sensitivity of 72.7% and a specificity of
      86.0%. A factor analysis suggested multidimensionality with two factors (anxiety
      and depression). CONCLUSIONS: the EPDS showed good validity in the postnatal
      period in a clinical sample in Hungary.

PMID- 24742636
TI  - Relationship between complementary and alternative medicine use and incidence of
      adverse birth outcomes: an examination of a nationally representative sample of
      1835 Australian women.
AB  - OBJECTIVE: there is evidence of high use of complementary and alternative
      medicine (CAM) by pregnant women. Despite debate and controversy regarding CAM
      use in pregnancy there has been little research focus upon the impacts of CAM use
      on birth outcomes. This paper reports findings outlining the incidence of adverse
      birth outcomes among women accessing CAM during pregnancy. DESIGN: a survey-based
      cohort sub-study from the nationally-representative Australian Longitudinal Study
      on Women's Health (ALSWH) was undertaken in 2010. PARTICIPANTS: women (aged 31-36
      years) who identified in 2009 as pregnant or recently given birth (n=2445) from
      the younger cohort (n=8012) of ALSWH were recruited for the study. MEASUREMENTS
      AND FINDINGS: participants' responses were analysed to examine the relationship
      between use of CAM and adverse birth outcomes from their most recent pregnancy.
      Of the respondents (n=1835; 79.2%), there were variations in birth outcomes for
      the women who used different CAM. Notably, the outcome which was most commonly
      associated with CAM use was emotional distress. This was found to occur more
      commonly in women who practised meditation/yoga at home, used flower essences, or
      consulted with a chiropractor. In contrast, women who consulted with a
      chiropractor or consumed herbal teas were less likely to report a premature
      birth, whilst participation in yoga classes was associated with an increased
      incidence of post partum/intrapartum haemorrhage. KEY CONCLUSIONS: the results
      emphasise the necessity for further research evaluating the safety and
      effectiveness of CAM for pregnant women, with a particular focus on birth
      outcomes. IMPLICATIONS FOR PRACTICE: health professionals providing care need to
      be aware of the potential birth outcomes associated with CAM use during pregnancy
      to enable the provision of accurate information to women in their care, and to
      assist in safely supporting women accessing CAM to assist with pregnancy, labour
      and birth.

PMID- 24742637
TI  - Midwives' experiences of workplace resilience.
AB  - BACKGROUND: many UK midwives experience workplace adversity resulting from a
      national shortage of midwives, rise in birth rate and increased numbers of women
      entering pregnancy with complex care needs. Research evidence suggests that
      workplace pressures, and the emotional demands of the job, may increase midwives'
      experience of stress and contribute to low morale, sickness and attrition. Much
      less is known about midwives who demonstrate resilience in the face of adversity.
      Resilience has been investigated in studies of other health and social care
      workers, but there is a gap in knowledge regarding midwives' experiences.
      OBJECTIVE: to explore clinical midwives' understanding and experience of
      professional resilience and to identify the personal, professional and contextual
      factors considered to contribute to or act as barriers to resilience. DESIGN: an
      exploratory qualitative descriptive study. In Stage One, a closed online
      professional discussion group was conducted over a one month period. Midwives
      discussed workplace adversity and their resilient responses to this. In Stage
      Two, the data were discussed with an Expert Panel with representatives from
      midwifery workforce and resilience research, in order to enhance data
      interpretation and refine the concept modelling. SETTING: the online discussion
      group was hosted by the Royal College of Midwives, UK online professional
      networking hub: 'Communities'. PARTICIPANTS: 11 practising midwives with 15 or
      more years of 'hands on clinical experience', and who self-identified as being
      resilient, took part in the online discussion group. FINDINGS: thematic analysis
      of the data identified four themes: challenges to resilience, managing and
      coping, self-awareness and building resilience. The participants identified
      'critical moments' in their careers when midwives were especially vulnerable to
      workplace adversity. Resilience was seen as a learned process which was
      facilitated by a range of coping strategies, including accessing support and
      developing self-awareness and protection of self. The participants identified the
      importance of a strong sense of professional identity for building resilience.
      KEY CONCLUSIONS: this study provides important new insights into resilience
      within UK midwifery, of relevance to the wider profession. Some findings echo
      those of other resilience studies; however, there are new insights such as the
      importance of professional identity which may be relevant to other health care
      workers. Through understanding more about resilience, it may be possible to
      facilitate positive adaptation by midwives and ameliorate the effects of
      workplace adversity. IMPLICATIONS FOR PRACTICE: This study indicates that
      resilience is a complex phenomenon, which warrants serious consideration from
      clinical midwives, managers, educators and researchers.

PMID- 24742638
TI  - Differences between the fourth and fifth Korotkoff phases among children and
      adolescents.
AB  - BACKGROUND: The relative importance of the fourth (K4) and fifth (K5) Korotkoff
      phases as the indicator of diastolic blood pressure (DBP) levels among children
      remains uncertain. METHODS: In a sample of 11,525 youth aged 5-17, we examined
      interexaminer differences in these 2 phases and the relation of theses 2 phases
      to adult blood pressure levels and hypertension. The longitudinal analyses were
      conducted among 2,156 children who were re-examined after age 25 years. RESULTS:
      Mean (+/-SD) levels of DBP were 62 (+/-9) mm Hg (K4) and 49 (+/-13) mm Hg (K5).
      K4 showed less interobserver variability than did K5, and 7% of the children had
      at least 1 (of 6) K5 value of 0mm Hg. Longitudinal analyses indicated that K4 was
      more strongly associated with adult blood pressure levels and hypertension. In
      correlational analyses of subjects who were not using antihypertensive
      medications in adulthood (n = 1,848), K4 was more strongly associated with the
      adult DBP level than was K5 (r = 0.22 vs. 0.17; P < 0.01). Analyses of adult
      hypertension (based on high blood pressure levels or use of antihypertensive
      medications) indicated that the screening performance of childhood levels of K4
      was similar to that of systolic blood pressure and was higher than that of K5,
      with areas under the receiver operator characteristic curves of 0.63 (systolic
      blood pressure), 0.63 (K4), and 0.57 (K5). CONCLUSIONS: As compared with K5
      levels among children, K4 shows less interobserver variability and is more
      strongly associated with adult hypertension.

PMID- 24742639
TI  - Actions of circulating angiotensin II and aldosterone in the brain contributing
      to hypertension.
AB  - In the past 1-2 decades, it has become apparent that the brain renin-angiotensin
      aldosterone system (RAAS) plays a crucial role in the regulation of blood
      pressure (BP) by the circulating RAAS. In the brain, angiotensinergic sympatho
      excitatory pathways do not contribute to acute, second-to-second regulation but
      play a major role in the more chronic regulation of the setpoint for sympathetic
      tone and BP. Increases in plasma angiotensin II (Ang II) or aldosterone and in
      cerebrospinal fluid [Na(+)] can directly activate these pathways and chronically
      further activate/maintain enhanced activity by a slow neuromodulatory pathway
      involving local aldosterone, mineralocorticoid receptors (MRs), epithelial sodium
      channels, and endogenous ouabain. Blockade of any step in this slow pathway
      prevents Ang II-, aldosterone-, or salt and renal injury-induced forms of
      hypertension. It appears that the renal and arterial actions of circulating
      aldosterone and Ang II act as amplifiers but are not sufficient to cause chronic
      hypertension if their central actions are prevented, except perhaps at high
      concentrations. From a clinical perspective, oral treatment with an angiotensin
      type 1 (AT1)-receptor blocker at high doses can cause central AT1-receptor
      blockade and, in humans, lower sympathetic nerve activity. Low doses of the MR
      blocker spironolactone appear sufficient to cause central MR blockade and a
      decrease in sympathetic nerve activity. Integrating the brain actions of the
      circulating RAAS with its direct renal and arterial actions provides a better
      framework to understand the role of the circulating RAAS in the pathophysiology
      of hypertension and heart failure and to direct therapeutic strategies. 

PMID- 24742647
TI  - Reduced intensity conditioning and hematopoietic stem cell transplantation in
      pediatric nonmalignant disease: a new therapeutic paradigm.

PMID- 24742640
TI  - The histone demethylase JMJD1A induces cell migration and invasion by up
      regulating the expression of the long noncoding RNA MALAT1.
AB  - Patients with neuroblastoma due to N-Myc oncogene amplification have a high
      frequency of tumor metastasis. However, it is not clear how N-Myc induces cell
      migration, invasion and metastasis. The histone demethylase JMJD1A activates gene
      transcription by demethylating the lysine 9 residue of histone H3 (H3K9) at
      target gene promoters. The long noncoding RNA MALAT1 induces lung cancer cell
      migration and plays a pivotal role in lung cancer metastasis. Here we
      demonstrated that N-Myc up-regulated the expression of JMJD1A in N-Myc oncogene
      amplified human neuroblastoma cells by directly binding to the JMJD1A gene
      promoter. Affymetrix microarray studies revealed that the gene second most
      significantly up-regulated by JMJD1A was MALAT1. Consistent with this finding, RT
      PCR and chromatin immunoprecipitation assays showed that JMJD1A bound to the
      MALAT1 gene promoter and demethylated histone H3K9 at the MALAT1 gene promoter.
      Moreover, JMJD1A and MALAT1 induced, while the small molecule JMJD1A inhibitor
      DMOG suppressed, neuroblastoma cell migration and invasion. Taken together, our
      data identify a novel pathway through which N-Myc causes neuroblastoma cell
      migration and invasion, and provide important evidence for further development of
      more potent JMJD1A/MALAT1 inhibitors for the prevention of tumor metastasis. 

PMID- 24742648
TI  - 50 years ago in the journal of pediatrics: the hemolytic-uremic syndrome.

PMID- 24742649
TI  - 50 years ago in the journal of pediatrics: the route of insulin administration in
      the management of diabetes mellitus.

PMID- 24742650
TI  - 50 years ago in the journal of pediatrics: convulsive equivalent syndrome of
      childhood.

PMID- 24742651
TI  - 50 years ago in the journal of pediatrics: pulmonary artery banding for
      persistent truncus arteriosus.

PMID- 24742652
TI  - Hypotonic IV fluid administration is associated with hyponatremia.

PMID- 24742653
TI  - Distinguishing features of cardiac-related syncope.

PMID- 24742654
TI  - No association of HPV vaccination with serious adverse events.

PMID- 24742655
TI  - Flow resistant caps prevent the rapid ingestion of liquid medicine.

PMID- 24742656
TI  - Soda consumption is associated with negative behavior in young children.

PMID- 24742657
TI  - Cannabinoid inhibits HIV-1 Tat-stimulated adhesion of human monocyte-like cells
      to extracellular matrix proteins.
AB  - AIMS: The aim of this study was to assess the effect of select cannabinoids on
      human immunodeficiency virus type 1 (HIV-1) transactivating (Tat) protein
      enhanced monocyte-like cell adhesion to proteins of the extracellular matrix
      (ECM). MAIN METHODS: Collagen IV, laminin, or an ECM gel was used to construct
      extracellular matrix layers. Human U937 monocyte-like cells were exposed to Tat
      in the presence of ?(9)-tetrahydrocannabinol (THC), CP55,940, and other select
      cannabinoids. Cell attachment to ECM proteins was assessed using an adhesion
      assay. KEY FINDINGS: THC and CP55,940 inhibited Tat-enhanced attachment of U937
      cells to ECM proteins in a mode that was linked to the cannabinoid receptor type
      2 (CB2R). The cannabinoid treatment of Tat-activated U937 cells was associated
      with altered beta1-integrin expression and distribution of polymerized actin,
      suggesting a modality by which these cannabinoids inhibited adhesion to the ECM.
      SIGNIFICANCE: The blood-brain barrier (BBB) is a complex structure that is
      composed of cellular elements and an extracellular matrix (ECM). HIV-1 Tat
      promotes transmigration of monocytes across this barrier, a process that includes
      interaction with ECM proteins. The results indicate that cannabinoids that
      activate the CB2R inhibit the ECM adhesion process. Thus, this receptor has
      potential to serve as a therapeutic agent for ablating neuroinflammation
      associated with HIV-elicited influx of monocytes across the BBB.

PMID- 24742658
TI  - Elevated serum free light chains predict cardiovascular events in type 2
      diabetes.
AB  - OBJECTIVE: Elevated polyclonal serum immunoglobulin free light chains (FLCs;
      combined FLCkappa+FLClambda [cFLC]) are associated with adverse clinical outcomes
      and increased mortality; we investigated cFLC and cardiovascular disease (CVD)
      events in type 2 diabetes. RESEARCH DESIGN AND METHODS: In a cohort study of 352
      south Asian patients with type 2 diabetes, serum cFLC, high-sensitivity C
      reactive protein (hsCRP), and standard biochemistry were measured. CVD events
      over 2 years were recorded and assessed using multiple logistic regression.
      RESULTS: cFLC levels were elevated significantly in 29 of 352 (8%) patients with
      CVD events during 2 years of follow-up (50.7 vs. 42.8 mg/L; P = 0.004). In
      multivariate analysis, elevated cFLC (>57.2 mg/L) was associated with CVD
      outcomes (odds ratio 3.3 [95% CI 1.3-8.2]; P = 0.012) and remained significant
      after adjusting for age, albumin-to-creatinine ratio, diabetes duration, or
      treatment. CONCLUSIONS: cFLC elevation is a novel marker for CVD outcomes in type
      2 diabetes that warrants further investigation.

PMID- 24742659
TI  - Youth overweight and metabolic disturbances in predicting carotid intima-media
      thickness, type 2 diabetes, and metabolic syndrome in adulthood: the
      Cardiovascular Risk in Young Finns study.
AB  - OBJECTIVE: Our objective was to assess cardiovascular risk and metabolic
      complications in adulthood in subjects with or without overweight and metabolic
      disturbances (i.e., elevated blood pressure, glucose, triglycerides, low HDL
      cholesterol, and high LDL cholesterol) and their combinations as youth. RESEARCH
      DESIGN AND METHODS: Using data from the population-based Cardiovascular Risk in
      Young Finns study, we examined the utility of four age- and sex-specific youth
      phenotypes (group I: normal weight, no metabolic disturbances; group II: normal
      weight, one or more metabolic disturbances; group III: overweight/obese, no
      metabolic disturbances; group IV: overweight/obese, one or more metabolic
      disturbances) in predicting adult high carotid intima-media thickness (IMT), type
      2 diabetes mellitus (T2DM), and metabolic syndrome (MetS). The study included
      1,617 participants 9-24 years of age at baseline who were followed up 21-25 years
      later. RESULTS: IMT (mean +/- SEM) was higher among participants in groups II
      (0.627 +/- 0.005 mm, P = 0.05), III (0.647 +/- 0.010 mm, P = 0.005), and IV
      (0.670 +/- 0.010 mm, P < 0.0001) compared with group I (0.616 +/- 0.003 mm). In
      addition, subjects in group IV had significantly higher IMT compared with those
      in group II (P = 0.002). Participants in groups II, III, and IV were at increased
      risk of the development of MetS in adulthood compared with those in the control
      group. For group II participants, the difference was attenuated after risk factor
      adjustments. Additionally, participants in group III and IV were at increased
      risk of the development of T2DM compared with those in groups I and II.
      CONCLUSIONS: While metabolic risk factors associated with overweight increase
      future risk for MetS, T2DM, and increased IMT, overweight in isolation is also a
      risk factor. Therefore, overweight should be prevented and treated wherever
      possible.

PMID- 24742660
TI  - Efficacy and safety of dulaglutide versus sitagliptin after 52 weeks in type 2
      diabetes in a randomized controlled trial (AWARD-5).
AB  - OBJECTIVE: To compare the efficacy and safety of two doses of once-weekly
      dulaglutide, a glucagon-like peptide 1 receptor agonist, to sitagliptin in
      uncontrolled, metformin-treated patients with type 2 diabetes. The primary
      objective was to compare (for noninferiority and then superiority) dulaglutide
      1.5 mg versus sitagliptin in change from baseline in glycosylated hemoglobin A1c
      (HbA1c) at 52 weeks. RESEARCH DESIGN AND METHODS: This multicenter, adaptive,
      double-blind, parallel-arm study randomized patients (N = 1,098; mean baseline
      age 54 years; HbA1c 8.1% [65 mmol/mol]; weight 86.4 kg; diabetes duration 7
      years) to dulaglutide 1.5 mg, dulaglutide 0.75 mg, sitagliptin 100 mg, or placebo
      (placebo-controlled period up to 26 weeks). The treatment period lasted 104
      weeks, with 52-week primary end point data presented. RESULTS: The mean HbA1c
      changes to 52 weeks were (least squares mean +/- SE): -1.10 +/- 0.06% (-12.0 +/-
      0.7 mmol/mol), -0.87 +/- 0.06% (9.5 +/- 0.7 mmol/mol), and -0.39 +/- 0.06% (4.3
      +/- 0.7 mmol/mol) for dulaglutide 1.5 mg, dulaglutide 0.75 mg, and sitagliptin,
      respectively. Both dulaglutide doses were superior to sitagliptin (P < 0.001,
      both comparisons). No events of severe hypoglycemia were reported. Mean weight
      changes to 52 weeks were greater with dulaglutide 1.5 mg (-3.03 +/- 0.22 kg) and
      dulaglutide 0.75 mg (-2.60 +/- 0.23 kg) compared with sitagliptin (-1.53 +/- 0.22
      kg) (P < 0.001, both comparisons). The most common gastrointestinal treatment
      emergent adverse events in dulaglutide 1.5- and 0.75-mg arms were nausea,
      diarrhea, and vomiting. CONCLUSIONS: Both dulaglutide doses demonstrated superior
      glycemic control versus sitagliptin at 52 weeks with an acceptable tolerability
      and safety profile.

PMID- 24742661
TI  - Circulating concentrations of soluble receptor for AGE are associated with age
      and AGER gene polymorphisms in children with newly diagnosed type 1 diabetes.
AB  - OBJECTIVE: We analyzed the relationship among soluble receptor for advanced
      glycation end products (sRAGEs), the clinical phenotype, HLA genotype, and risk
      associated single nucleotide polymorphisms (SNPs) in the AGER gene in a large
      population of Finnish children with newly diagnosed type 1 diabetes. RESEARCH
      DESIGN AND METHODS: Samples from 2,115 clinically phenotyped children <15 years
      of age in whom type 1 diabetes was diagnosed and 316 control subjects were
      analyzed for sRAGEs. Three SNPs of AGER, previously associated with HLA-DR/DQ
      haplotype independent diabetes risk (rs2070600, rs9469089, and rs17493811), were
      analyzed in 1,390 affected subjects. RESULTS: Children with type 1 diabetes and
      control subjects had similar sRAGE concentrations (1,171 vs. 1,153 pg/mL, P =
      0.48). There was a correlation between age at diagnosis and serum sRAGE
      concentrations (r = 0.10, P < 0.001) among the patients but not among the control
      subjects. Children <2 years of age had the lowest concentrations in the diabetic
      population (1,027 vs. 1,181 pg/mL, P < 0.001) and the highest among the control
      subjects (1,329 vs. 1,140 pg/mL, P = 0.04). Ketoacidosis at diagnosis was
      associated with reduced concentrations (1,086 vs. 1,190 pg/mL, P < 0.001). HLA
      DR3/DR4 heterozygosity and the DR3 allele were associated with reduced sRAGE
      concentrations. The predisposing AA genotype of rs2070600 was associated with
      decreased sRAGE concentrations, while the protective CC genotype of rs9469089 was
      linked to increased concentrations. CONCLUSIONS: Age and AGER polymorphisms are
      associated with the circulating sRAGE concentration among children with type 1
      diabetes. The observations of reduced sRAGE concentrations in young children, in
      those with ketoacidosis, and in carriers of the high-risk HLA DR3/DR4 genotype
      suggest that decreased sRAGE concentration reflects a more aggressive disease
      phenotype.

PMID- 24742662
TI  - AUTONOMY: the first randomized trial comparing two patient-driven approaches to
      initiate and titrate prandial insulin lispro in type 2 diabetes.
AB  - OBJECTIVE: To compare two self-titration algorithms for initiating and escalating
      prandial insulin lispro in patients with type 2 diabetes inadequately controlled
      on basal insulin. RESEARCH DESIGN AND METHODS: The trial was designed as two
      independent, multinational, parallel, open-label studies (A and B), identical in
      design, to provide substantial evidence of efficacy and safety in endocrine and
      generalist settings. Subjects were 18-85 years old (study A: N = 528; study B: N
      = 578), on basal insulin plus oral antidiabetic drugs for >=3 months, and had an
      HbA1c 7.0% to <=12.0% (>53.0 to <=107.7 mmol/mol). Once optimized on insulin
      glargine, subjects were randomized to one of two self-titration algorithm groups
      adjusting lispro either every day (Q1D) or every 3 days (Q3D) for 24 weeks. The
      primary outcome was the change in HbA1c from baseline. The primary and secondary
      objectives were evaluated for the overall population and subjects >=65 years old.
      RESULTS: Baseline HbA1c was similar (study A: Q1D 8.3% [67.2 mmol/mol] vs. Q3D
      8.4% [68.3 mmol/mol], P = 0.453; study B: Q1D 8.3% [67.2 mmol/mol] vs. Q3D 8.4%
      [68.3 mmol/mol], P = 0.162). Both algorithms had significant and equivalent
      reductions in HbA1c from baseline (study A: Q3D -0.96% [-10.49 mmol/mol], Q1D 
      1.00% [-10.93 mmol/mol], Q3D-Q1D 0.04% [0.44 mmol/mol] [95% CI -0.15 to 0.22 (
      1.64 to 2.40)]; study B: Q3D -0.92% [-10.06 mmol/mol], Q1D -0.98% [-10.71
      mmol/mol], Q3D-Q1D 0.06% [0.66 mmol/mol] [95% CI -0.12 to 0.24 (-1.31 to 2.62)]).
      The incidence and rate of hypoglycemia were similar for Q3D and Q1D in both
      studies. In general, no clinically relevant differences were found between the
      two algorithms in subjects >=65 years old in either study. CONCLUSIONS: Prandial
      insulin lispro can effectively and safely be initiated, by either of two self
      titrated algorithms, in a variety of practice settings.

PMID- 24742663
TI  - Large personalised medicine trial in lung cancer heralds new research
      partnership.

PMID- 24742664
TI  - Study on the interaction of the toxic food additive carmoisine with serum
      albumins: a microcalorimetric investigation.
AB  - The interaction of the synthetic azo dye and food colorant carmoisine with human
      and bovine serum albumins was studied by microcalorimetric techniques. A complete
      thermodynamic profile of the interaction was obtained from isothermal titration
      calorimetry studies. The equilibrium constant of the complexation process was of
      the order of 10(6)M(-1) and the binding stoichiometry was found to be 1:1 with
      both the serum albumins. The binding was driven by negative standard molar
      enthalpy and positive standard molar entropy contributions. The binding affinity
      was lower at higher salt concentrations in both cases but the same was dominated
      by mostly non-electrostatic forces at all salt concentrations. The
      polyelectrolytic forces contributed only 5-8% of the total standard molar Gibbs
      energy change. The standard molar enthalpy change enhanced whereas the standard
      molar entropic contribution decreased with rise in temperature but they
      compensated each other to keep the standard molar Gibbs energy change almost
      invariant. The negative standard molar heat capacity values suggested the
      involvement of a significant hydrophobic contribution in the complexation
      process. Besides, enthalpy-entropy compensation phenomenon was also observed in
      both the systems. The thermal stability of the serum proteins was found to be
      remarkably enhanced on binding to carmoisine. 

PMID- 24742665
TI  - Behavior of oxyfluorfen in soils amended with different sources of organic
      matter. Effects on soil biology.
AB  - We performed a laboratory study on the effect of oxyfluorfen at a rate of 4lha(
      1) on biological properties of a soil amended with four organic wastes (two
      biostimulants/biofertilizers, obtained from rice bran, RB1 and RB2; municipal
      solid waste, MSW; and sheep manure, SM). Soil was mixed with SM at a rate of 1%,
      MSW at a rate of 0.52%, RB1 at a rate of 0.39% and RB2 at a rate of 0.30%, in
      order to apply the same amount of organic matter to the soil. The enzymatic
      activities and microbial community in the soil were determined during the
      incubation times. The application of RB1 and RB2 to soil without oxyfluorfen
      increased the enzymatic activities and biodiversity, peaking at day 10 of the
      incubation period. This stimulation was higher in the soil amended with RB2 than
      in that amended with RB1. In SM and CF-amended soils, the stimulation of
      enzymatic activities and soil biodiversity increased during the experiment. The
      application of herbicide in organic-amended soils decreased the inhibition of
      soil enzymatic activities and soil biodiversity. Possibly the low molecular
      weight protein content easily assimilated by soil microorganisms and the higher
      fat content in the biostimulants/biofertilizers are responsible for the lower
      inhibition of these soil biological properties. 

PMID- 24742666
TI  - The lateralized smell test for detecting Alzheimer's disease: failure to
      replicate.
AB  - OBJECTIVES: A widely publicized study by Stamps, Bartoshuk and Heilman (2013)
      reported that a simple measure of left:right naris differences in the ability to
      detect the odor of peanut butter is a sensitive marker of Alzheimer's disease
      (AD). AD patients were said to have abnormal smell function on the left side of
      the nose and normal function on right side of the nose. In light of its
      implications for medical practice and the world-wide publicity that it
      engendered, we sought to replicate and expand this work. METHODS: Two studies
      were performed. In the first, 15 AD patients were tested according to the
      procedures described by Stamps et al. in which the nostril contralateral to the
      tested side was occluded by the patient using lateral pressure from the index
      finger. Since this can potentially distort the contralateral naris, we repeated
      the testing using tape for naris occlusion. In the second, 20 AD patients were
      administered 20 odors of the University of Pennsylvania Smell Identification Test
      (UPSIT) to each side of the nose, with the contralateral naris being closed with
      tape. In both studies, the order of the side of testing was systematically
      counterbalanced. RESULTS: No evidence of a left:right asymmetry on any test
      measure was observed. CONCLUSION: Although hyposmia is well-established in AD, no
      meaningful asymmetry in smell perception is apparent. If olfactory function on
      the right side of the nose was normal as claimed, then AD patients should exhibit
      normal function when tested bilaterally, a phenomenon not seen in dozens of AD
      related olfactory studies.

PMID- 24742667
TI  - Protein N-glycosylation in oral cancer: dysregulated cellular networks among
      DPAGT1, E-cadherin adhesion and canonical Wnt signaling.
AB  - N-Linked glycosylation (N-glycosylation) of proteins has long been associated
      with oncogenesis, but not until recently have the molecular mechanisms underlying
      this relationship begun to be unraveled. Here, we review studies describing how
      dysregulation of the N-glycosylation-regulating gene, DPAGT1, drives oral cancer.
      DPAGT1 encodes the first and rate-limiting enzyme in the assembly of the lipid
      linked oligosaccharide precursor in the endoplasmic reticulum and thus mediates N
      glycosylation of many cancer-related proteins. DPAGT1 controls N-glycosylation of
      E-cadherin, the major epithelial cell-cell adhesion receptor and a tumor
      suppressor, thereby affecting intercellular adhesion and cytoskeletal dynamics.
      DPAGT1 also regulates and is regulated by Wnt/beta-catenin signaling, impacting
      the balance between proliferation and adhesion in homeostatic tissues. Thus,
      aberrant induction of DPAGT1 promotes a positive feedback network with Wnt/beta
      catenin that represses E-cadherin-based adhesion and drives tumorigenic
      phenotypes. Further, modification of receptor tyrosine kinases (RTKs) with N
      glycans is known to control their surface presentation via the galectin lattice,
      and thus increased DPAGT1 expression likely contributes to abnormal activation of
      RTKs in oral cancer. Collectively, these studies suggest that dysregulation of
      the DPAGT1/Wnt/E-cadherin network underlies the etiology and pathogenesis of oral
      cancer. 

PMID- 24742668
TI  - The role of select subtype polymorphisms on HIV-1 protease conformational
      sampling and dynamics.
AB  - HIV-1 protease is an essential enzyme for viral particle maturation and is a
      target in the fight against HIV-1 infection worldwide. Several natural
      polymorphisms are also associated with drug resistance. Here, we utilized both
      pulsed electron double resonance, also called double electron-electron resonance,
      and NMR (15)N relaxation measurements to characterize equilibrium conformational
      sampling and backbone dynamics of an HIV-1 protease construct containing four
      specific natural polymorphisms commonly found in subtypes A, F, and CRF_01 A/E.
      Results show enhanced backbone dynamics, particularly in the flap region, and the
      persistence of a novel conformational ensemble that we hypothesize is an
      alternative flap orientation of a curled open state or an asymmetric
      configuration when interacting with inhibitors. 

PMID- 24742669
TI  - Residue histidine 50 plays a key role in protecting alpha-synuclein from
      aggregation at physiological pH.
AB  - alpha-Synuclein (alphaSyn) aggregation is involved in the pathogenesis of
      Parkinson disease (PD). Recently, substitution of histidine 50 in alphaSyn with a
      glutamine, H50Q, was identified as a new familial PD mutant. Here, nuclear
      magnetic resonance (NMR) studies revealed that the H50Q substitution causes an
      increase of the flexibility of the C-terminal region. This finding provides
      direct evidence that this PD-causing mutant can mediate long range effects on the
      sampling of alphaSyn conformations. In vitro aggregation assays showed that
      substitution of His-50 with Gln, Asp, or Ala promotes alphaSyn aggregation,
      whereas substitution with the positively charged Arg suppresses alphaSyn
      aggregation. Histidine carries a partial positive charge at neutral pH, and so
      our result suggests that positively charged His-50 plays a role in protecting
      alphaSyn from aggregation under physiological conditions. 

PMID- 24742670
TI  - Mint proteins are required for synaptic activity-dependent amyloid precursor
      protein (APP) trafficking and amyloid beta generation.
AB  - Aberrant amyloid beta (Abeta) production plays a causal role in Alzheimer disease
      pathogenesis. A major cellular pathway for Abeta generation is the activity
      dependent endocytosis and proteolytic cleavage of the amyloid precursor protein
      (APP). However, the molecules controlling activity-dependent APP trafficking in
      neurons are less defined. Mints are adaptor proteins that directly interact with
      the endocytic sorting motif of APP and are functionally important in regulating
      APP endocytosis and Abeta production. We analyzed neuronal cultures from control
      and Mint knockout neurons that were treated with either glutamate or tetrodotoxin
      to stimulate an increase or decrease in neuronal activity, respectively. We found
      that neuronal activation by glutamate increased APP endocytosis, followed by
      elevated APP insertion into the cell surface, stabilizing APP at the plasma
      membrane. Conversely, suppression of neuronal activity by tetrodotoxin decreased
      APP endocytosis and insertion. Interestingly, we found that activity-dependent
      APP trafficking and Abeta generation were blocked in Mint knockout neurons. We
      showed that wild-type Mint1 can rescue APP internalization and insertion in Mint
      knockout neurons. In addition, we found that Mint overexpression increased
      excitatory synaptic activity and that APP was internalized predominantly to
      endosomes associated with APP processing. We demonstrated that presenilin 1 (PS1)
      endocytosis requires interaction with the PDZ domains of Mint1 and that this
      interaction facilitates activity-dependent colocalization of APP and PS1. These
      findings demonstrate that Mints are necessary for activity-induced APP and PS1
      trafficking and provide insight into the cellular fate of APP in endocytic
      pathways essential for Abeta production. 

PMID- 24742671
TI  - Glycogen synthase kinase-3beta stabilizes the interleukin (IL)-22 receptor from
      proteasomal degradation in murine lung epithelia.
AB  - Signaling through the interleukin (IL)-22 cytokine axis provides essential immune
      protection in the setting of extracellular infection as part of type 17 immunity.
      Molecular regulation of IL-22 receptor (IL-22R) protein levels is unknown. In
      murine lung epithelia, IL-22R is a relatively short-lived protein (t1/2 ~1.5 h)
      degraded by the ubiquitin proteasome under normal unstimulated conditions, but
      its degradation is accelerated by IL-22 treatment. Lys(449) within the
      intracellular C-terminal domain of the IL-22R serves as a ubiquitin acceptor site
      as disruption of this site by deletion or site-directed mutagenesis creates an IL
      22R variant that, when expressed in cells, is degradation-resistant and not
      ubiquitinated. Glycogen synthase kinase (GSK)-3beta phosphorylates the IL-22R
      within a consensus phosphorylation signature at Ser(410) and Ser(414), and IL-22
      treatment of cells triggers GSK-3beta inactivation. GSK-3beta overexpression
      results in accumulation of IL-22R protein, whereas GSK-3beta depletion in cells
      reduces levels of the receptor. Mutagenesis of IL-22R at Ser(410) and Ser(414)
      results in receptor variants that display reduced phosphorylation levels and are
      more labile as compared with wild-type IL-22R when expressed in cells. Further,
      the cytoskeletal protein cortactin, which is important for epithelial spreading
      and barrier formation, is phosphorylated and activated at the epithelial cell
      leading edge after treatment with IL-22, but this effect is reduced after GSK
      3beta knockdown. These findings reveal the ability of GSK-3beta to modulate IL
      22R protein stability that might have significant implications for cytoprotective
      functions and therapeutic targeting of the IL-22 signaling axis. 

PMID- 24742672
TI  - Divergent roles for adiponectin receptor 1 (AdipoR1) and AdipoR2 in mediating
      revascularization and metabolic dysfunction in vivo.
AB  - Adiponectin is a well described anti-inflammatory adipokine that is highly
      abundant in serum. Previous reports have found that adiponectin deficiency
      promotes cardiovascular and metabolic dysfunction in murine models, whereas its
      overexpression is protective. Two candidate adiponectin receptors, AdipoR1 and
      AdipoR2, are uncharacterized with regard to cardiovascular tissue homeostasis,
      and their in vivo metabolic functions remain controversial. Here we subjected
      AdipoR1- and AdipoR2-deficient mice to chronic hind limb ischemic surgery. Blood
      flow recovery in AdipoR1-deficient mice was similar to wild-type; however,
      revascularization in AdipoR2-deficient mice was severely attenuated. Treatment
      with adiponectin enhanced the recovery of wild-type mice but failed to rescue the
      impairment observed in AdipoR2-deficient mice. In view of this divergent receptor
      function in the hind limb ischemia model, AdipoR1- and AdipoR2-deficient mice
      were also evaluated in a model of diet-induced obesity. Strikingly, AdipoR1
      deficient mice developed severe metabolic dysfunction compared with wild type,
      whereas AdipoR2-deficient mice were protected from diet-induced weight gain and
      metabolic perturbations. These data show that AdipoR2, but not AdipoR1, is
      functionally important in an in vivo model of ischemia-induced revascularization
      and that its expression is essential for the revascularization actions of
      adiponectin. These data also show that, in contrast to revascularization
      responses, AdipoR1, but not AdipoR2 deficiency, leads to diet-induced metabolic
      dysfunction, revealing that these receptors have highly divergent roles in
      vascular and metabolic homeostasis. 

PMID- 24742673
TI  - Indomethacin treatment prevents high fat diet-induced obesity and insulin
      resistance but not glucose intolerance in C57BL/6J mice.
AB  - Chronic low grade inflammation is closely linked to obesity-associated insulin
      resistance. To examine how administration of the anti-inflammatory compound
      indomethacin, a general cyclooxygenase inhibitor, affected obesity development
      and insulin sensitivity, we fed obesity-prone male C57BL/6J mice a high fat/high
      sucrose (HF/HS) diet or a regular diet supplemented or not with indomethacin (+/
      INDO) for 7 weeks. Development of obesity, insulin resistance, and glucose
      intolerance was monitored, and the effect of indomethacin on glucose-stimulated
      insulin secretion (GSIS) was measured in vivo and in vitro using MIN6 beta-cells.
      We found that supplementation with indomethacin prevented HF/HS-induced obesity
      and diet-induced changes in systemic insulin sensitivity. Thus, HF/HS+INDO-fed
      mice remained insulin-sensitive. However, mice fed HF/HS+INDO exhibited
      pronounced glucose intolerance. Hepatic glucose output was significantly
      increased. Indomethacin had no effect on adipose tissue mass, glucose tolerance,
      or GSIS when included in a regular diet. Indomethacin administration to obese
      mice did not reduce adipose tissue mass, and the compensatory increase in GSIS
      observed in obese mice was not affected by treatment with indomethacin. We
      demonstrate that indomethacin did not inhibit GSIS per se, but activation of
      GPR40 in the presence of indomethacin inhibited glucose-dependent insulin
      secretion in MIN6 cells. We conclude that constitutive high hepatic glucose
      output combined with impaired GSIS in response to activation of GPR40-dependent
      signaling in the HF/HS+INDO-fed mice contributed to the impaired glucose
      clearance during a glucose challenge and that the resulting lower levels of
      plasma insulin prevented the obesogenic action of the HF/HS diet. 

PMID- 24742674
TI  - Rapid production of platelet-activating factor is induced by protein kinase
      Calpha-mediated phosphorylation of lysophosphatidylcholine acyltransferase 2
      protein.
AB  - Platelet-activating factor (PAF), a potent proinflammatory lipid mediator, is
      synthesized rapidly in response to extracellular stimuli by the activation of
      acetyl-CoA:lyso-PAF acetyltransferase (lyso-PAFAT). We have reported previously
      that lyso-PAFAT activity is enhanced in three distinct ways in mouse macrophages:
      rapid activation (30 s) after PAF stimulation and minutes to hours after LPS
      stimulation. Lysophosphatidylcholine acyltransferase 2 (LPCAT2) was later
      identified as a Ca(2+)-dependent lyso-PAFAT. However, the mechanism of rapid lyso
      PAFAT activation within 30 s has not been elucidated. Here we show a new
      signaling pathway for rapid biosynthesis of PAF that is mediated by
      phosphorylation of LPCAT2 at Ser-34. Stimulation by either PAF or ATP resulted in
      PKCalpha-mediated phosphorylation of LPCAT2 to enhance lyso-PAFAT activity and
      rapid PAF production. Biochemical analyses showed that the phosphorylation of Ser
      34 resulted in augmentation of Vmax with minimal Km change. Our results offer an
      answer for the previously unknown mechanism of rapid PAF production. 

PMID- 24742675
TI  - N-glycan remodeling on glucagon receptor is an effector of nutrient sensing by
      the hexosamine biosynthesis pathway.
AB  - Glucose homeostasis in mammals is dependent on the opposing actions of insulin
      and glucagon. The Golgi N-acetylglucosaminyltransferases encoded by Mgat1, Mgat2,
      Mgat4a/b/c, and Mgat5 modify the N-glycans on receptors and solute transporter,
      possibly adapting activities in response to the metabolic environment. Herein we
      report that Mgat5(-/-) mice display diminished glycemic response to exogenous
      glucagon, together with increased insulin sensitivity. Glucagon receptor
      signaling and gluconeogenesis in Mgat5(-/-) cultured hepatocytes was impaired. In
      HEK293 cells, signaling by ectopically expressed glucagon receptor was increased
      by Mgat5 expression and GlcNAc supplementation to UDP-GlcNAc, the donor substrate
      shared by Mgat branching enzymes. The mobility of glucagon receptor in primary
      hepatocytes was reduced by galectin-9 binding, and the strength of the
      interaction was dependent on Mgat5 and UDP-GlcNAc levels. Finally, oral GlcNAc
      supplementation rescued the glucagon response in Mgat5(-/-) hepatocytes and mice,
      as well as glycolytic metabolites and UDP-GlcNAc levels in liver. Our results
      reveal that the hexosamine biosynthesis pathway and GlcNAc salvage contribute to
      glucose homeostasis through N-glycan branching on glucagon receptor. 

PMID- 24742676
TI  - Fat-specific protein 27 inhibits lipolysis by facilitating the inhibitory effect
      of transcription factor Egr1 on transcription of adipose triglyceride lipase.
AB  - Lipolysis in fat tissue represents a major source of circulating fatty acids.
      Previously, we have found that lipolysis in adipocytes is controlled by early
      growth response transcription factor Egr1 that directly inhibits transcription of
      adipose triglyceride lipase, ATGL (Chakrabarti, P., Kim, J. Y., Singh, M., Shin,
      Y. K., Kim, J., Kumbrink, J., Wu, Y., Lee, M. J., Kirsch, K. H., Fried, S. K.,
      and Kandror, K. V. (2013) Mol. Cell. Biol. 33, 3659-3666). Here we demonstrate
      that knockdown of the lipid droplet protein FSP27 (a.k.a. CIDEC) in human
      adipocytes increases expression of ATGL at the level of transcription, whereas
      overexpression of FSP27 has the opposite effect. FSP27 suppresses the activity of
      the ATGL promoter in vitro, and the proximal Egr1 binding site is responsible for
      this effect. FSP27 co-immunoprecipitates with Egr1 and increases its association
      with and inhibition of the ATGL promoter. Knockdown of Egr1 attenuates the
      inhibitory effect of FSP27. These results provide a new model of transcriptional
      regulation of ATGL. 

PMID- 24742677
TI  - Alteration of the glucagon axis in GPR120 (FFAR4) knockout mice: a role for
      GPR120 in glucagon secretion.
AB  - GPR40 (FFAR1) and GPR120 (FFAR4) are G-protein-coupled receptors (GPCRs) that are
      activated by long chain fatty acids (LCFAs). GPR40 is expressed at high levels in
      islets and mediates the ability of LCFAs to potentiate glucose-stimulated insulin
      secretion (GSIS). GPR120 is expressed at high levels in colon, adipose, and
      pituitary, and at more modest levels in pancreatic islets. The role of GPR120 in
      islets has not been explored extensively. Here, we confirm that saturated (e.g.
      palmitic acid) and unsaturated (e.g. docosahexaenoic acid (DHA)) LCFAs engage
      GPR120 and demonstrate that palmitate- and DHA-potentiated glucagon secretion are
      greatly reduced in isolated GPR120 KO islets. Remarkably, LCFA potentiated
      glucagon secretion is similarly reduced in GPR40 KO islets. Compensatory changes
      in mRNA expression of GPR120 in GPR40 KO islets, and vice versa, do not explain
      that LCFA potentiated glucagon secretion seemingly involves both receptors. LCFA
      potentiated GSIS remains intact in GPR120 KO islets. Consistent with previous
      reports, GPR120 KO mice are hyperglycemic and glucose intolerant; however, our KO
      mice display evidence of a hyperactive counter-regulatory response rather than
      insulin resistance during insulin tolerance tests. An arginine stimulation test
      and a glucagon challenge confirmed both increases in glucagon secretion and liver
      glucagon sensitivity in GPR120 KO mice relative to WT mice. Our findings
      demonstrate that GPR120 is a nutrient sensor that is activated endogenously by
      both saturated and unsaturated long chain fatty acids and that an altered
      glucagon axis likely contributes to the impaired glucose homeostasis observed in
      GPR120 KO mice. 

PMID- 24742678
TI  - Glutathione-dependent one-electron transfer reactions catalyzed by a B12
      trafficking protein.
AB  - CblC is involved in an early step in cytoplasmic cobalamin processing following
      entry of the cofactor into the cytoplasm. CblC converts the cobalamin cargo
      arriving from the lysosome to a common cob(II)alamin intermediate, which can be
      subsequently converted to the biologically active forms. Human CblC exhibits
      glutathione (GSH)-dependent alkyltransferase activity and flavin-dependent
      reductive decyanation activity with cyanocobalamin (CNCbl). In this study, we
      discovered two new GSH-dependent activities associated with the Caenorhabditis
      elegans CblC for generating cob(II)alamin: decyanation of CNCbl and reduction of
      aquocobalamin (OH2Cbl). We subsequently found that human CblC also catalyzes GSH
      dependent decyanation of CNCbl and reduction of OH2Cbl, albeit efficiently only
      under anaerobic conditions. The air sensitivity of the human enzyme suggests
      interception by oxygen during the single-electron transfer step from GSH to
      CNCbl. These newly discovered GSH-dependent single-electron transfer reactions
      expand the repertoire of catalytic activities supported by CblC, a versatile B12
      processing enzyme. 

PMID- 24742679
TI  - Do lipids show state-dependent affinity to the voltage-gated potassium channel
      KvAP?
AB  - As all integral membrane proteins, voltage-gated ion channels are embedded in a
      lipid matrix that regulates their channel behavior either by physicochemical
      properties or by direct binding. Because manipulation of the lipid composition in
      cells is difficult, we investigated the influence of different lipids on purified
      KvAP channels reconstituted in planar lipid bilayers of known composition. Lipids
      developed two distinct and independent effects on the KvAP channels; lipids
      interacting with the pore lowered the energy barriers for the final transitions,
      whereas voltage sensor-bound lipids shifted the midpoint of activation dependent
      on their electrostatic charge. Above all, the midpoint of activation was
      determined only by those lipids the channels came in contact with first after
      purification and can seemingly only be exchanged if the channel resides in the
      open state. The high affinity of the bound lipids to the binding site has
      implications not only on our understanding of the gating mechanism but also on
      the general experimental design of any lipid dependence study. 

PMID- 24742680
TI  - Structural basis for the recognition of peptide RJPXD33 by acyltransferases in
      lipid A biosynthesis.
AB  - UDP-N-acetylglucosamine acyltransferase (LpxA) and UDP-3-O-(acyl)-glucosamine
      acyltransferase (LpxD) constitute the essential, early acyltransferases of lipid
      A biosynthesis. Recently, an antimicrobial peptide inhibitor, RJPXD33, was
      identified with dual affinity for LpxA and LpxD. To gain a fundamental
      understanding of the molecular basis of inhibitor binding, we determined the
      crystal structure of LpxA from Escherichia coli in complex with RJPXD33 at 1.9 A
      resolutions. Our results suggest that the peptide binds in a unique modality that
      mimics (R)-beta-hydroxyacyl pantetheine binding to LpxA and displays how the
      peptide binds exclusive of the native substrate, acyl-acyl carrier protein.
      Acyltransferase binding studies with photo-labile RJPXD33 probes and truncations
      of RJPXD33 validated the structure and provided fundamental insights for future
      design of small molecule inhibitors. Overlay of the LpxA-RJPXD33 structure with
      E. coli LpxD identified a complementary peptide binding pocket within LpxD and
      serves as a model for further biochemical characterization of RJPXD33 binding to
      LpxD. 

PMID- 24742681
TI  - Oxysterol-binding protein (OSBP)-related protein 4 (ORP4) is essential for cell
      proliferation and survival.
AB  - Oxysterol-binding protein (OSBP) and OSBP-related proteins (ORPs) comprise a
      large gene family with sterol/lipid transport and regulatory activities. ORP4
      (OSBP2) is a closely related paralogue of OSBP, but its function is unknown. Here
      we show that ORP4 binds similar sterol and lipid ligands as OSBP and other ORPs
      but is uniquely required for the proliferation and survival of cultured cells.
      Recombinant ORP4L and a variant without a pleckstrin homology (PH) domain (ORP4S)
      bind 25-hydroxycholesterol and extract and transfer cholesterol between
      liposomes. Two conserved histidine residues in the OSBP homology domain ORP4 are
      essential for binding phosphatidylinositol 4-phosphate but not sterols. The PH
      domain of ORP4L also binds phosphatidylinositol 4-phosphate in the Golgi
      apparatus. However, in the context of ORP4L, the PH domain is required for normal
      organization of the vimentin network. Unlike OSBP, RNAi silencing of all ORP4
      variants (including a partial PH domain truncation termed ORP4M) in HEK293 and
      HeLa cells resulted in growth arrest but not cell death. ORP4 silencing in non
      transformed intestinal epithelial cells (IEC)-18 caused apoptosis characterized
      by caspase 3 and poly(ADP-ribose) polymerase processing, DNA cleavage, and JNK
      phosphorylation. IEC-18 transformed with oncogenic H-Ras have increased
      expression of ORP4L and ORP4S proteins and are resistant to the growth-inhibitory
      effects of ORP4 silencing. Results suggest that ORP4 promotes the survival of
      rapidly proliferating cells. 

PMID- 24742682
TI  - Targeted silencing of anthrax toxin receptors protects against anthrax toxins.
AB  - Anthrax spores can be aerosolized and dispersed as a bioweapon. Current
      postexposure treatments are inadequate at later stages of infection, when high
      levels of anthrax toxins are present. Anthrax toxins enter cells via two
      identified anthrax toxin receptors: tumor endothelial marker 8 (TEM8) and
      capillary morphogenesis protein 2 (CMG2). We hypothesized that host cells would
      be protected from anthrax toxins if anthrax toxin receptor expression was
      effectively silenced using RNA interference (RNAi) technology. Thus, anthrax
      toxin receptors in mouse and human macrophages were silenced using targeted
      siRNAs or blocked with specific antibody prior to challenge with anthrax lethal
      toxin. Viability assays were used to assess protection in macrophages treated
      with specific siRNA or antibody as compared with untreated cells. Silencing CMG2
      using targeted siRNAs provided almost complete protection against anthrax lethal
      toxin-induced cytotoxicity and death in murine and human macrophages. The same
      results were obtained by prebinding cells with specific antibody prior to
      treatment with anthrax lethal toxin. In addition, TEM8-targeted siRNAs also
      offered significant protection against lethal toxin in human macrophage-like
      cells. Furthermore, silencing CMG2, TEM8, or both receptors in combination was
      also protective against MEK2 cleavage by lethal toxin or adenylyl cyclase
      activity by edema toxin in human kidney cells. Thus, anthrax toxin receptor
      targeted RNAi has the potential to be developed as a life-saving, postexposure
      therapy against anthrax. 

PMID- 24742683
TI  - Structure and function of the catalytic domain of the dihydrolipoyl
      acetyltransferase component in Escherichia coli pyruvate dehydrogenase complex.
AB  - The Escherichia coli pyruvate dehydrogenase complex (PDHc) catalyzing conversion
      of pyruvate to acetyl-CoA comprises three components: E1p, E2p, and E3. The E2p
      is the five-domain core component, consisting of three tandem lipoyl domains
      (LDs), a peripheral subunit binding domain (PSBD), and a catalytic domain
      (E2pCD). Herein are reported the following. 1) The x-ray structure of E2pCD
      revealed both intra- and intertrimer interactions, similar to those reported for
      other E2pCDs. 2) Reconstitution of recombinant LD and E2pCD with E1p and E3p into
      PDHc could maintain at least 6.4% activity (NADH production), confirming the
      functional competence of the E2pCD and active center coupling among E1p, LD,
      E2pCD, and E3 even in the absence of PSBD and of a covalent link between domains
      within E2p. 3) Direct acetyl transfer between LD and coenzyme A catalyzed by
      E2pCD was observed with a rate constant of 199 s(-1), comparable with the rate of
      NADH production in the PDHc reaction. Hence, neither reductive acetylation of E2p
      nor acetyl transfer within E2p is rate-limiting. 4) An unprecedented finding is
      that although no interaction could be detected between E1p and E2pCD by itself, a
      domain-induced interaction was identified on E1p active centers upon assembly
      with E2p and C-terminally truncated E2p proteins by hydrogen/deuterium exchange
      mass spectrometry. The inclusion of each additional domain of E2p strengthened
      the interaction with E1p, and the interaction was strongest with intact E2p. E2p
      domain-induced changes at the E1p active site were also manifested by the
      appearance of a circular dichroism band characteristic of the canonical 4'
      aminopyrimidine tautomer of bound thiamin diphosphate (AP). 

PMID- 24742684
TI  - Cell surface translocation of annexin A2 facilitates glutamate-induced
      extracellular proteolysis.
AB  - Glutamate-induced elevation in intracellular Ca(2+) has been implicated in
      excitotoxic cell death. Neurons respond to increased glutamate levels by
      activating an extracellular proteolytic cascade involving the components of the
      plasmin-plasminogen system. AnxA2 is a Ca(2+)-dependent phospholipid binding
      protein and serves as an extracellular proteolytic center by recruiting the
      tissue plasminogen activator and plasminogen and mediating the localized
      generation of plasmin. Ratiometric Ca(2+) imaging and time-lapse confocal
      microscopy demonstrated glutamate-induced Ca(2+) influx. We showed that glutamate
      translocated both endogenous and AnxA2-GFP to the cell surface in a process
      dependent on the activity of the NMDA receptor. Glutamate-induced translocation
      of AnxA2 is dependent on the phosphorylation of tyrosine 23 at the N terminus,
      and mutation of tyrosine 23 to a non-phosphomimetic variant inhibits the
      translocation process. The cell surface-translocated AnxA2 forms an active
      plasmin-generating complex, and this activity can be neutralized by a hexapeptide
      directed against the N terminus. These results suggest an involvement of AnxA2 in
      potentiating glutamate-induced cell death processes. 

PMID- 24742685
TI  - Dyadic Profiles of Parental Disciplinary Behavior and Links With Parenting
      Context.
AB  - Using data from couples (N = 1,195) who participated in a large community-based
      study of families, we used maternal reports of parental discipline to examine
      mothers' and fathers' use of and patterns related to aggressive and nonviolent
      discipline of their 3-year-old child. First, we separately examined mothers' and
      fathers' patterns, or classes, of disciplinary behaviors. Second, we identified
      joint mother-father class profiles. Maternal reports indicated that the patterns
      among fathers and mothers were similar, but fathers were more likely to be in the
      low-aggression classes than mothers; and mothers were more likely to be in the
      high-aggression classes than fathers. Dyads in which both parents employed high
      levels of aggressive discipline were characterized by higher parenting stress,
      poorer parental relationship, and lower quality community context. The majority
      (81.2%) of dyads used congruent disciplinary behaviors. Discordant dyads were
      similar to dyads in which both parents were high in aggressive discipline, in
      that these groups had children with the highest levels of aggressive behavior.
      Implications highlight the need to target both mothers and fathers with parent
      education efforts to reinforce positive parenting.

PMID- 24742686
TI  - Gradual proportion congruent effects in the absence of sequential congruent
      effects.
AB  - In perceptual filtering tasks, congruency effects vary as a function of
      proportion congruent (PC), with smaller congruency effects when congruent trials
      are rare than when they are frequent. This effect is typically larger with
      extreme differences between high and low proportion congruent conditions (e.g.,
      80% congruent-20% incongruent) than with intermediate differences (e.g., 60%
      congruent-40% incongruent; Logan & Zbofroff, 1979; Blais & Bunge, 2010). Some
      authors have claimed that both PC effects can be explained in terms of the same
      reactive cognitive control mechanism that is responsible for sequential
      congruency (SC) effects (e.g., Botvinick, Braver, Barch, Carter, & Cohen, 2001).
      In fact, in most previous studies there was a systematic confounding between
      proportion congruent and the proportion of transitions involving an incongruent
      trial followed by another incongruent trial. In the present study we eliminated
      this confound and tested directly whether PC effects can still be measured in the
      absence of SC effects. Once confirmed, we studied the properties of this pure
      form of PC effect, in particular whether it is conflict-type specific or general,
      and whether it decreases gradually as a function of changes in proportion
      congruency (80% vs. 70% vs. 60%). Our results showed significant PC effects in
      the absence of SC effects, which replicates our previous findings (Torres
      Quesada, Milliken, Lupianez, & Funes, 2014), and PC effects that can be conflict
      type general or specific, depending on the nature of conflict type where they
      were produced. Importantly, the congruency effect was modulated by the level of
      proportion congruent, decreasing systematically as the absolute percentage of
      incongruent trials decreases. 

PMID- 24742687
TI  - Improving early detection of childhood depression in mental health care: the
      Children's Depression Screener (ChilD-S).
AB  - Diagnosing childhood depression can pose a challenge, even for mental health
      specialists. Screening tools can aid clinicians within the initial step of the
      diagnostic process. For the first time, the Children's Depression Screener (ChilD
      S) is validated in a mental health setting as a novel field of application beyond
      the previously examined pediatric setting. Based on a structured interview, DSM
      IV-TR diagnoses of depression were made for 79 psychiatric patients aged 9-12,
      serving as the gold standard for validation. For assessing criterion validity,
      receiver operating characteristic (ROC) curves were calculated. Point prevalence
      of major depression and dysthymia was 28%. Diagnostic accuracy in terms of the
      area under the ROC curve was high (0.97). At the optimal cut-off point >=12
      according to the Youden's index, sensitivity was 0.91 and specificity was 0.81.
      The findings suggest that the ChilD-S is not only a valid screening instrument
      for childhood depression in pediatric care but also in mental health settings. As
      a brief tool it can easily be implemented into daily clinical practice of mental
      health professionals facilitating the diagnostic process, especially in case of
      comorbid depression. 

PMID- 24742688
TI  - Waiting for a heart or lung transplant: Relatives' experience of information and
      support.
AB  - OBJECTIVES: To describe the relatives' experiences of information and support
      while heart or lung transplant candidates were waiting for a transplantation.
      METHODOLOGY/DESIGN: The critical incident technique was used. Incidents were
      collected via interviews with 18 relatives (28-73 years old) of heart or lung
      transplant patients within four weeks of the patients being accepted onto the
      transplant waiting list. FINDINGS: A total of 286 important events, both positive
      and negative, were identified and divided into two main areas: "Experiencing
      information and support" and "Reflecting upon information and support."
      "Experiencing information and support" was associated with "dissatisfaction with
      the health-care system", "being relatively satisfied", "supporting patients" and
      "the role of social networks." "Reflecting upon information and support" was
      associated with "finding strength" and "uncomfortable with emotions". Relatives
      experiences suggest that needs can be met through specific targeted information
      and support for them as well as mediating contact to previously transplanted
      persons. CONCLUSION: The findings indicate a gap between the information and
      support that relatives need and receive, and that more attention should be paid
      to information and support for this group. By increasing awareness among
      healthcare professionals and the community, interventions can be developed that
      benefit relatives.

PMID- 24742690
TI  - A novel supermicrosurgery training model: the chicken thigh.
AB  - BACKGROUND: Supermicrosurgery is an increasingly important technique in
      reconstructive surgery. It requires a more technically refined skill set compared
      with standard microsurgery. All currently available biologic training models
      involve the use of live rats. A nonliving model would be more accessible and cost
      effective for practice. We have developed such a model using chicken thighs
      purchased from a local grocery store. METHODS: The ischiatic neurovascular bundle
      was identified in 20 chicken thighs and dissected distally to the end of the
      specimen. The vessel diameters were measured at several points along the artery,
      vein, and their respective branches. Vessels with diameters in the 0.3-0.8-mm
      range were then divided and supermicrosurgical anastomoses were attempted.
      RESULTS: The branching pattern of the ischiatic artery and vein were anatomically
      consistent with intermediate and terminal secondary and tertiary branches
      consistently in the range of 0.3-0.8 mm. In all specimens, at least one 0.3-mm
      vessel could be identified, though additional intramuscular dissection was
      sometimes required. It was demonstrated that supermicrosurgical anastomoses could
      be successfully performed using these branches. CONCLUSIONS: This study
      introduces a novel, convenient, and economical model for supermicrosurgery
      utilizing easily obtained chicken thighs. The chicken thighs have an anatomically
      consistent vascular branching pattern, and vessels of appropriate sizes for
      training can be easily identified and isolated. Surgeons looking to develop or
      refine supermicrosurgical skills may find this nonliving, biologic model very
      useful.

PMID- 24742691
TI  - Avoiding pitfalls in open augmentation rhinoplasty with autologous L-shaped
      costal cartilage strut grafts for saddle nose collapse due to autoimmune disease:
      the Cambridge experience.
AB  - INTRODUCTION: Saddle nose deformity due to autoimmune diseases such as Wegener's
      Granulomatosis and Relapsing Polychondritis is aesthetically, functionally and
      psychologically distressing for patients. However, "reliable" options for
      surgical correction remain limited in the literature. We present our experience
      of augmentation rhinoplasty in this patient population focussing on the
      techniques and pitfalls of L-shaped costal cartilage grafting. METHODS: Five
      patients undergoing rhinoplasty for saddle nose deformity due to an autoimmune
      condition were identified over an 11-year period at a major tertiary centre. All
      patients were in remission from their condition at surgery and underwent L-shaped
      costal cartilage grafting at augmentation rhinoplasty. Case notes were reviewed
      retrospectively. RESULTS: All patients achieved a marked improvement in nasal
      position, shape and contour and were very pleased with their overall appearance.
      The average length of follow up was 2.8 years. There were no infections, graft
      exposure or warping. No resorption of cartilage was observed and there have been
      no recurrent deformities. CONCLUSION: This case series describes a possible
      approach to corrective rhinoplasty in patients with saddle nose deformity caused
      by autoimmune disease, highlighting the key technical steps and potential
      pitfalls of intraoperative and perioperative care in this population. The
      approach is straightforward, reproducible, and achieved pleasing aesthetic
      outcomes and high patient satisfaction. Given careful planning and meticulous
      execution, L-strut cartilage grafts for augmentation rhinoplasty to correct
      saddle nose deformity in these patients is of great benefit. LEVEL OF EVIDENCE:
      Therapeutic Study Level IV, case series with pre/post test.

PMID- 24742692
TI  - Functional reconstruction of the deltoid muscle following complete resection of
      musculoskeletal sarcoma.
AB  - Although the deltoid muscle has been assumed to be an essential shoulder muscle,
      the full extent of postoperative functions of the upper extremity following its
      complete resection due to sarcoma has not been thoroughly investigated. In this
      study, we review patients who underwent wide resection for sarcoma in the deltoid
      muscle, followed by functional reconstruction using pedicled latissimus dorsi
      (LD) muscle transfer. Four patients with sarcoma arising in the deltoid muscle
      were reviewed. Tumor resection with a wide surgical margin resulted in loss of
      the entire deltoid muscle together with the axillary nerve. For reconstruction,
      the ipsilateral pedicled LD muscle was transferred on its neurovascular pedicle
      for use as a functional substitute. One case had local recurrence and the
      transferred LD myocutaneous flap was resected. There were no serious
      complications after the operation, and all flaps survived perfectly. Wound
      healing at both the recipient and donor sites was uneventful. Active abduction of
      the shoulder joint was >160 degrees  in all patients. The muscle manual test of
      shoulder flexion was good to normal and abduction was fair to good.
      Musculoskeletal Tumor Society scores were excellent in all cases and the average
      score was 92% (range, 87-93%). Our results suggest that removal of the entire
      deltoid muscle resulted in a slight impairment of function. Pedicled LD
      musculocutaneous flaps are useful for covering the defect that results from
      resection of the deltoid muscle and they contribute additional function to the
      affected shoulder.

PMID- 24742693
TI  - To thin or not to thin: a case of peripartum cardiomyopathy.
AB  - We describe the case of a 29-year-old woman with peripartum cardiomyopathy (PPCM)
      complicated by multiple cerebral infarcts. Current treatment of PPCM is reviewed
      with a focus on the role of anticoagulation in PPCM. 

PMID- 24742694
TI  - SIRT1 promotes proliferation and inhibits the senescence-like phenotype in human
      melanoma cells.
AB  - SIRT1 operates as both a tumor suppressor and oncogenic factor depending on the
      cell context. Whether SIRT1 plays a role in melanoma biology remained poorly
      elucidated. Here, we demonstrate that SIRT1 is a critical regulator of melanoma
      cell proliferation. SIRT1 suppression by genetic or pharmacological approaches
      induces cell cycle arrest and a senescence-like phenotype. Gain and loss of
      function experiments show that M-MITF regulates SIRT1 expression, thereby
      revealing a melanocyte-specific control of SIRT1. SIRT1 over-expression relieves
      the senescence-like phenotype and the proliferation arrest caused by MITF
      suppression, demonstrating that SIRT1 is an effector of MITF-induced
      proliferation in melanoma cells. Interestingly, SIRT1 level and activity are
      enhanced in the PLX4032-resistant BRAF(V600E)-mutated melanoma cells compared
      with their sensitive counterpart. SIRT1 inhibition decreases melanoma cell growth
      and rescues the sensibility to PLX4032 of PLX4032-resistant BRAF(V600E)-mutated
      melanoma cells. In conclusion, we provide the first evidence that inhibition of
      SIRT1 warrants consideration as an anti-melanoma therapeutic option.

PMID- 24742695
TI  - Long-term immunosuppression and malignancy in thoracic transplantation: where is
      the balance?
AB  - Cancers in post-transplant patients exhibit the same molecular and cellular
      properties as those in their non-transplanted counterparts and arise secondary to
      uncontrolled/sustained growth, apoptosis resistance, inhibition of tumor
      suppressors, immortalization of cells with invasion, and and metastasis.
      Disruption of DNA repair mechanisms, upregulation of angiogenic growth factors,
      impaired viral immunity and activated oncogenic viruses contribute to the
      initiation of malignancies in this population. This article extends and addresses
      the concerns in this area. We propose potential cancer prevention strategies and
      a possible 4-pronged approach to prevent and treat malignancies in the post
      transplant population. Future research should define strategies for immune
      modulation, immune suppression and malignancy prevention, including methods for
      naive B-cell repopulation, memory B-cell reduction and biomarker identification
      and utilization for predicting tolerance. Non-immune therapies, such as adjunct
      preventive methods and goals to modify risk factors, may reduce incidence of
      malignancies and pave the way to better outcomes. The role of statins is of
      particular interest in this context due to their pleiotropic effects on the cell
      cycle and their most direct role in inhibition of cholesterol biosynthesis. 

PMID- 24742696
TI  - Microparticles and left ventricular assist device complications: a causal
      association?

PMID- 24742697
TI  - Donor fecal transfer for recurrent Clostridium difficile-associated diarrhea in
      heart transplantation.

PMID- 24742698
TI  - Are panoramic radiographs predictive of temporomandibular joint synovitis in
      children with juvenile idiopathic arthritis?
AB  - PURPOSE: To identify specific panoramic radiographic findings associated with
      temporomandibular joint (TMJ) synovitis in children with juvenile idiopathic
      arthritis (JIA). MATERIALS AND METHODS: This was a retrospective study of
      children with JIA evaluated at Boston Children's Hospital. Patients were included
      if they had a confirmed diagnosis of JIA, a panoramic radiograph, and a
      contemporaneous TMJ magnetic resonance imaging (MRI) study with contrast. Medical
      records and imaging studies were reviewed to document demographic, panoramic
      (accentuated antegonial notch, short ramus and condyle unit [RCU] length, and
      abnormal condyle morphology: decreased condyle anteroposterior or superoinferior
      dimension) and MRI findings. The outcome variable was the presence or absence of
      TMJ synovitis on MRI. Descriptive and bivariate statistics and logistic
      regression models were used to identify associations (significant at P <= .05).
      RESULTS: Thirty patients (21 girls) with a mean age of 11.1 years (range, 5 to 16
      yr) met the inclusion criteria. Of these, 15 patients had MRI scans positive for
      synovitis (bilateral in 18 joints in 9 patients and unilateral in 6 joints in 6
      patients). The remaining 15 patients did not have evidence of synovitis on MRI.
      In the synovitis group, 18 of 24 joints (75%) showed abnormal panoramic findings
      (abnormal condyle morphology in 18 joints, accentuated antegonial notch in 9
      joints, or short RCU length in 5 joints). In the nonsynovitis group, 15 of 36
      joints (42%) showed abnormal panoramic findings (abnormal condyle morphology in
      12 joints, accentuated antegonial notch in 6 joints, or short RCU length in 4
      joints). Abnormal condyle morphology and accentuated antegonial notching on
      panoramic radiographs were found to be significantly correlated with synovitis (P
      = .0005 and .044, respectively). In a logistic regression model, abnormal condyle
      morphology was significantly associated with an increase in likelihood of TMJ
      synovitis versus those joints with normal condyle morphology (P = .007). Joints
      with abnormal condyle morphology and accentuated antegonial notching were 7.5
      times as likely to have synovitis (P = .009) versus those joints without abnormal
      panoramic findings. CONCLUSION: Results of this preliminary study indicate that
      in this sample of children with JIA, the combination of abnormal condyle
      morphology and accentuated antegonial notching on a panoramic radiograph
      correlates with TMJ synovitis on MRI.

PMID- 24742699
TI  - Use of the matching optimal symmetry plane method in planning surgical correction
      of facial asymmetry--a preliminary report of 20 patients.
AB  - PURPOSE: A voxel-based median plane (optimal symmetry plane [OSP]) was developed
      to assess facial bone asymmetry. The purpose of the present study was to
      introduce a new method of planning surgical correction of facial asymmetry using
      the OSPs as guides and test its effectiveness. PATIENTS AND METHODS: A
      retrospective study was conducted of 20 facial asymmetry patients with a
      mandibular deviation of 4 mm or greater or 4 degrees  or more that required
      surgical correction. In the test group (n = 8), the plans for asymmetry
      correction were formulated using the matching OSP method, in which the OSPs of
      the facial bones are tracked and matched during the model surgery setup. In the
      control group (n = 12), traditional planning was conducted. The traditional plans
      were cross-checked for symmetry through tracking and revised as needed. The
      symmetry results of the plans were compared between the 2 groups and within the
      control group. The outcome measures were the deviation distances between the OSPs
      of the midface and mandible at the anterior or posterior mandible, the occlusal
      plane cant, and the angle formed by the 2 OSPs. Surgery was performed in
      accordance with the final plans, and the results were assessed for symmetry.
      RESULTS: The traditional plans left a major mandibular deviation in 5 of the 12
      control subjects compared with none in the test group. The test group did
      significantly better than the control group. The revised plans were significantly
      better than the initial plans. Postoperatively, significant improvements in
      symmetry were observed. CONCLUSION: The new method resulted in surgical plans
      that brought about significantly less postoperative mandibular deviation while
      maintaining a reasonable occlusion.

PMID- 24742700
TI  - Lithocholic acid feeding results in direct hepato-toxicity independent of
      neutrophil function in mice.
AB  - Lithocholic acid (LCA) supplementation in the diet results in intrahepatic
      cholestasis and bile infarcts. Previously we showed that an innate immune
      response is critical for cholestatic liver injury in the bile duct ligated mice.
      Thus, the purpose of this study was to investigate the role of neutrophils in the
      mechanism of liver injury caused by feeding mice a diet containing LCA. C57BL/6
      mice were given control or 1% LCA containing diet for 24-96 h and then examined
      for parameters of hepatotoxicity. Plasma ALT levels were significantly increased
      by 48 h after LCA feeding, which correlated with both neutrophil recruitment to
      the liver and upregulation of numerous pro-inflammatory genes. The injury was
      confirmed by histology. Deficiency in intercellular adhesion molecule-1 (ICAM-1)
      expression or inhibition of neutrophil function failed to protect against the
      injury. Bile acid levels were quantified in plasma and bile of LCA-fed mice after
      48 and 96 h. Only the observed biliary levels of taurochenodeoxycholic acid and
      potentially tauro-LCA caused direct cytotoxicity in mouse hepatocytes. These data
      support the conclusion that neutrophil recruitment occurs after the onset of bile
      acid-induced necrosis in LCA-fed animals, and is not a primary mechanism of cell
      death when cholestasis occurs through accumulation of hydrophobic bile acids.

PMID- 24742701
TI  - A mutually beneficial relationship between hepatocytes and cardiomyocytes
      mitigates doxorubicin-induced toxicity.
AB  - Use of doxorubicin (DOX) is limited by its toxicity in multiple organs. However,
      the relationship between different organs in response to DOX-induced injury is
      not well understood. We found that partial hepatectomy correlated with increased
      DOX-induced heart injury in vivo while supernatant prepared from DOX-treated
      hepatocytes mitigated DOX-induced cytotoxicity of cardiomyocytes in vitro.
      Meanwhile, the supernatant of DOX-treated cardiomyocytes mitigated DOX-induced
      cytotoxicity of hepatocytes. Investigation of the molecular mechanisms underlying
      these effects found that interleukin 6 (IL-6) was significantly up-regulated in
      DOX-treated tissues and cells, and supernatant from IL-6 treated cells had a
      similar effect to that from DOX-treated cells. Although the concentration of
      secreted IL-6 in supernatant from DOX-treated cells did not significantly differ,
      blockade of IL-6 signaling, by overexpressing SOCS3, suppressed expression of the
      downstream molecules trefoil factor family 3 (TFF3) and hepatocyte growth factor
      (HGF), impaired the mutually beneficial relationship between hepatocytes and
      cardiomyocytes. In conclusion, our study shows that a mutually beneficial
      relationship exists between hepatocytes and cardiomyocytes during the acute
      injury induced by DOX. Moreover, it demonstrates that this phenomenon may be
      indirectly caused by increased IL-6 expression and the activation of the
      downstream molecular mediators TFF3 and HGF in hepatocytes and cardiomyocytes,
      respectively. 

PMID- 24742702
TI  - Noninvasive examination of endothelial, sympathetic, and myogenic contributions
      to regional differences in the human cutaneous microcirculation.
AB  - The aim of this study was to examine whether there are regional differences in
      the cutaneous microvascular responses of the forearm and the leg. Utilizing a non
      invasive measure (spectral analysis),we looked at the influence of the
      endothelial, sympathetic, and myogenic function between regions at thermoneutral
      conditions (33  degrees C) and in response to local skin warming (42  degrees C)
      using laser-Doppler flowmetry (LDF). We recruited 18 young, healthy participants,
      who visited the lab on 2 separate occasions. Participants were instrumented with
      LDF probes and local skin heater probe-holders, placed on the forearm or the leg.
      Blood pressure was recorded by oscillometry. At both 33  degrees C and during
      local skin warming to 42  degrees C, skin vasomotion for the forearm and leg were
      evaluated using spectral analysis of the LDF recordings. There were significant
      differences among all frequencies of interest between the forearm and the leg. At
      33  degrees C the leg presented with higher (P=0.003) activity for endothelial
      (0.009-0.021 Hz), sympathetic (P=0.002) (0.021-0.052 Hz), and myogenic (P=0.004)
      (0.052-0.145 Hz) activity when compared to the forearm. In contrast, following 35
      min of local skin warming, the forearm had greater endothelial (P=0.019),
      sympathetic (P=0.006), and myogenic (P=0.005) vasomotion than the leg. These
      outcomes indicate regional differences in the cutaneous microcirculation. The
      current results are similar to our previous work using invasive methods and
      pharmacological agents, indicating that non-invasive analyses may be useful in
      the diagnoses and understanding of the mechanisms that control the microvascular
      function of pathological conditions.

PMID- 24742703
TI  - Reducing PEC uncertainty in coastal zones: a case study on carbamazepine,
      oxcarbazepine and their metabolites.
AB  - Concentrations of the antiepileptic drugs carbamazepine (Cbz), oxcarbazepine
      (OxCz) and their main metabolites were predicted in a wastewater treatment plant
      (WTP) and in the vicinity of its submarine outfall located in a Mediterranean
      coastal zone. Refined predicted environmental concentrations (PECs) were
      calculated in effluents based on consumption data and human excretion rates. PECs
      were estimated in the sea using the hydrodynamic MARS 3D model integrating
      meteorological data, oceanic conditions (wind, tide, atmospheric pressure),
      freshwater and sewage inputs. Measured environmental concentrations (MECs) were
      compared to PECs to assess the estimation relevance. In the coastal zone, PEC and
      MEC were in the same magnitude range. Modeling of Cbz diffusion and advection
      just above the submarine outfall showed the influence of the thermocline during
      summer, with low diffusion of Cbz from the bottom to the surface. This work
      allowed understanding the dispersion of target compounds and deserved further
      development for a better acknowledgement of vulnerability at local scales. 

PMID- 24742704
TI  - Treadmill training after surgical removal of a spinal tumor in infancy.
AB  - BACKGROUND AND PURPOSE: Step training on a treadmill is a common intervention for
      adult and pediatric patients with spinal cord injuries (SCI). Treadmill training
      has not been used as an intervention for infants and toddlers with SCI before
      walking onset. This case report describes the intervention and stepping behaviors
      on a treadmill and overground of a toddler after the surgical removal of a rare
      spinal tumor resulting in SCI. CASE DESCRIPTION: The toddler presented with an
      inability to step on the left, rare stepping on the right, and an apparent lack
      of sensation in the lower extremities. After spinal tumor excision at 5.5 weeks
      of age, step training on a treadmill and overground occurred once per week from
      15 to 35 months of age in addition to traditional physical therapy. OUTCOMES:
      Independent symmetrical stepping emerged both on and off the treadmill over 20
      months. Improvements in the number and pattern of steps occurred with training.
      Walking speed increased, and milestones important to overground walking
      developed. DISCUSSION: Independent steps developed during the intervention with
      little motor development of the lower extremities during the first year of life.
      Furthermore, improvements in stepping alternation, standing, and walking occurred
      despite no evidence of sensation in the lower extremities.

PMID- 24742705
TI  - Validating a simple discharge planning tool following hospital admission for an
      isolated lower limb fracture.
AB  - BACKGROUND: Early, accurate prediction of discharge destination from the acute
      hospital assists individual patients and the wider hospital system. The Trauma
      Rehabilitation and Prediction Tool (TRaPT), developed using registry data,
      determines probability of inpatient rehabilitation discharge for patients with
      isolated lower limb fractures. OBJECTIVE: The aims of this study were: (1) to
      prospectively validatate the TRaPT, (2) to assess whether its performance could
      be improved by adding additional demographic data, and (3) to simplify it for use
      as a bedside tool. DESIGN: This was a cohort, measurement-focused study. METHODS:
      Patients with isolated lower limb fractures (N=114) who were admitted to a major
      trauma center in Melbourne, Australia, were included. The participants' TRaPT
      scores were calculated from admission data. Performance of the TRaPT score alone,
      and in combination with frailty, weight-bearing status, and home supports, was
      assessed using measures of discrimination and calibration. A simplified TRaPT was
      developed by rounding the coefficients of variables in the original model and
      grouping age into 8 categories. Simplified TRaPT performance measures, including
      specificity, sensitivity, and positive and negative predictive values, were
      evaluated. RESULTS: Prospective validation of the TRaPT showed excellent
      discrimination (C-statistic=0.90 [95% confidence interval=0.82, 0.97]), a
      sensitivity of 80%, and specificity of 94%. All participants able to weight bear
      were discharged directly home. Simplified TRaPT scores had a sensitivity of 80%
      and a specificity of 88%. LIMITATIONS: Generalizability may be limited given the
      compensation system that exists in Australia, but the methods used will assist in
      designing a similar tool in any population. CONCLUSIONS: The TRaPT accurately
      predicted discharge destination for 80% of patients and may form a useful aid for
      discharge decision making, with the simplified version facilitating its use as a
      bedside tool.

PMID- 24742706
TI  - Estrogen restores brain insulin sensitivity in ovariectomized non-obese rats, but
      not in ovariectomized obese rats.
AB  - OBJECTIVE: We previously demonstrated that obesity caused the reduction of
      peripheral and brain insulin sensitivity and that estrogen therapy improved these
      defects. However, the beneficial effect of estrogen on brain insulin sensitivity
      and oxidative stress in either ovariectomy alone or ovariectomy with obesity
      models has not been determined. We hypothesized that ovariectomy alone or
      ovariectomy with obesity reduces brain insulin sensitivity and increases brain
      oxidative stress, which are reversed by estrogen treatment. MATERIALS/METHODS:
      Thirty female rats were assigned as either sham-operated or ovariectomized. After
      the surgery, each group was fed either a normal diet or high-fat diet for 12
      weeks. At week 13, rats in each group received either the vehicle or estradiol
      for 30 days. At week 16, blood and brain were collected for determining the
      peripheral and brain insulin sensitivity as well as brain oxidative stress.
      RESULTS: We found that ovariectomized rats and high-fat diet fed rats incurred
      obesity, reduced peripheral and brain insulin sensitivity, and increased brain
      oxidative stress. Estrogen ameliorated peripheral insulin sensitivity in these
      rats. However, the beneficial effect of estrogen on brain insulin sensitivity and
      brain oxidative stress was observed only in ovariectomized normal diet-fed rats,
      but not in ovariectomized high fat diet-fed rats. CONCLUSIONS: Our results
      suggested that reduced brain insulin sensitivity and increased brain oxidative
      stress occurred after either ovariectomy or obesity. However, the reduced brain
      insulin sensitivity and the increased brain oxidative stress in ovariectomy with
      obesity could not be ameliorated by estrogen treatment.

PMID- 24742707
TI  - The functional effect of a distal rectus femoris tenotomy in adults with cerebral
      palsy.
AB  - The purpose of this study was to determine the effect of a distal rectus femoris
      tenotomy on function and gait in adults with cerebral palsy who had diminished
      knee flexion during swing. A stiff knee gait pattern is commonly seen in
      individuals with cerebral palsy and frequently leads to tripping and falling.
      Five subjects, 25-51 years, (34.6+/-10.3 years) participated in the study; each
      individual had the surgery after the age of 18. Four of the five subjects
      underwent bilateral distal rectus femoris tenotomies for a total of nine limbs
      being studied. Four of the five subjects had a single procedure of a distal
      rectus femoris tenotomy and one subject also had bilateral adductor tenotomies.
      All individuals underwent a pre-operative and post-operative, (3.28+/-1.6 years)
      three-dimensional gait analysis. Pre-operative gait revealed diminished peak knee
      flexion and out of phase rectus femoris activity with a quiet vastus lateralis
      during swing in all subjects. Significant findings after a distal rectus femoris
      tenotomy included: improved peak swing knee flexion, improved peak stance hip
      extension, and increased total knee excursion without loss in knee extension
      strength. During swing, knee flexion angle improved on average 11 degrees  which
      correlated with subjective report of less shoe wear, tripping, and falling due to
      improved clearance. In conclusion, a distal rectus femoris tenotomy should be
      considered a surgical option for adults with cerebral palsy and a stiff knee gait
      pattern to improve mobility, function, and quality of life. 

PMID- 24742708
TI  - The risks of using "species-specific" PCR assays in wildlife research: The case
      of red fox (Vulpes vulpes) identification in Tasmania.

PMID- 24742710
TI  - Utilization of Rad51C promoter for transcriptional targeting of cancer cells.
AB  - Cancer therapy that specifically targets malignant cells with minimal or no
      toxicity to normal tissue has been a long-standing goal of cancer research. Rad51
      expression is elevated in a wide range of cancers and Rad51 promoter has been
      used to transcriptionally target tumor cells, however, a large size of Rad51
      promoter limits its application for gene therapy. To identify novel tumor
      specific promoters, we examined expression levels of Rad51 paralogs, Rad51B,
      Rad51C, and Rad51D as well as Rad52 in a panel of normal and tumor cell lines. We
      found that Rad51C is significantly overexpressed in cancer cells. The expression
      was up-regulated by approximately 6-fold at the mRNA level and 9-fold at the
      protein level. Interestingly, the 2064 bp long Rad51C promoter fragment was
      approximately 300-fold higher in cancer cells than in normal cells. A construct
      containing Rad51C promoter driving diphtheria toxin A efficiently killed several
      types of cancer cells with very mild effect to normal cells. These results
      underscore the potential of targeting the homologous recombination pathway in
      cancer cells and provide a proof of principle that the Rad51C promoter fragment
      can be used to transcriptionally target cancer cells. 

PMID- 24742712
TI  - Unraveling structural mechanisms of allosteric drug action.
AB  - Orthosteric drugs block the active site to obstruct function; allosteric drugs
      modify the population of the active state, to modulate function. Available data
      lead us to propose that allosteric drugs can constitute anchors and drivers. The
      anchor docks into an allosteric pocket. The conformation with which it interacts
      is unchanged during the transition between the inactive and active states. The
      anchor provides the foundation that allows the driver to exert a 'pull' and/or
      'push' action that shifts the receptor population from the inactive to the active
      state. The presence or absence of driver atom in an allosteric drug can exert
      opposite agonism. We map a strategy for driver identification and expect the
      allosteric trigger concept to transform agonist/antagonist drug discovery. 

PMID- 24742713
TI  - Simvastatin is associated with reduced risk of acute pancreatitis: findings from
      a regional integrated healthcare system.
AB  - OBJECTIVE: To characterise the relationship between simvastatin and risk of acute
      pancreatitis (AP). DESIGN: We conducted a retrospective cohort study (2006-2012)
      on data from an integrated healthcare system in southern California. Exposure to
      simvastatin was calculated from time of initial dispensation until 60 days
      following prescription termination. AP cases were defined by ICD-9 CM 577.0 and
      serum lipase>=3 times normal. Patients were censored at death, last follow-up,
      and onset of AP or end-of-study. Incidence rate of pancreatitis among simvastatin
      users was compared with the adult reference population. Robust Poisson regression
      was used to generate risk ratio (RR) estimates for simvastatin use adjusted for
      age, gender, race/ethnicity, gallstone-related disorders, hypertriglyceridaemia,
      smoking and alcohol dependence. Analysis was repeated for atorvastatin. RESULTS:
      Among 3,967,859 adult patients (median duration of follow-up of 3.4 years), 6399
      developed an initial episode of AP. A total of 707,236 patients received
      simvastatin during the study period. Patients that received simvastatin were more
      likely to have gallstone-related disorders, alcohol dependence or
      hypertriglyceridaemia compared with the reference population. Nevertheless, risk
      of AP was significantly reduced with simvastatin use, crude incidence rate ratio
      0.626 (95% CL 0.588, 0.668), p<0.0001. In multivariate analysis, simvastatin was
      independently associated with reduced risk of pancreatitis, adjusted RR 0.29 (95%
      CL 0.27, 0.31) after adjusting for age, gender, race/ethnicity, gallstone
      disorders, alcohol dependence, smoking and hypertriglyceridaemia. Similar results
      were noted with atorvastatin, adjusted RR 0.33(0.29, 0.38). CONCLUSIONS: Use of
      simvastatin was independently associated with reduced risk of AP in this
      integrated healthcare setting. Similar findings for atorvastatin suggest a
      possible class effect.

PMID- 24742714
TI  - Genistein inhibits phorbol ester-induced NF-kappaB transcriptional activity and
      COX-2 expression by blocking the phosphorylation of p65/RelA in human mammary
      epithelial cells.
AB  - Genistein, an isoflavone present in soy products, has chemopreventive effects on
      mammary carcinogenesis. In the present study, we have investigated the effects of
      genistein on phorbol ester-induced expression of cyclooxygenase-2 (COX-2) that
      plays an important role in the pathophysiology of inflammation-associated
      carcinogenesis. Pretreatment of cultured human breast epithelial (MCF10A) cells
      with genistein reduced COX-2 expression induced by 12-O-tetradecanoylphorbol-13
      acetate (TPA). There are multiple lines of evidence supporting that the induction
      of COX-2 is regulated by the eukaryotic transcription factor NF-kappaB. Genistein
      failed to inhibit TPA-induced nuclear translocation and DNA binding of NF-kappaB
      as well as degradation of IkappaB. However, genistein abrogated the TPA-induced
      transcriptional activity of NF-kappaB as determined by the luciferase reporter
      gene assay. Genistein inhibited phosphorylation of the p65 subunit of NF-kappaB
      and its interaction with cAMP regulatory element-binding protein-binding protein
      (CBP)/p300 and TATA-binding protein (TBP). TPA-induced NF-kappaB phosphorylation
      was abolished by pharmacological inhibition of extracellular signal-regulated
      kinase (ERK). Likewise, pharmacologic inhibition or dominant negative mutation of
      ERK suppressed phosphorylation of p65. The above findings, taken together,
      suggest that genistein inhibits TPA-induced COX-2 expression in MCF10A cells by
      blocking ERK-mediated phosphorylation of p65 and its subsequent interaction with
      CBP and TBP. 

PMID- 24742715
TI  - The training of future tissue pathologists in a changing world.

PMID- 24742716
TI  - Studies on drug-polymer interaction, in vitro release and cytotoxicity from
      chitosan particles excipient.
AB  - Nonobvious controlled polymeric pharmaceutical excipient, chitosan nanoparticles
      (CS-NPs) for lenalidomide encapsulation were geared up by the simple ionic cross
      linking method to get better bioavailability and to reduce under as well as
      overloading of hydrophobic and sparingly soluble drug lenalidomide towards cancer
      cells. Lenalidomide loaded chitosan nanoparticles (LND-CS-NPs) were in the size
      range of 220-295 nm and characterized by DLS, TEM, FT-IR, TGA and XRD.
      Encapsulation of lenalidomide over chitosan nanoparticles was observed about
      99.35% using UV spectrophotometry method. In vitro release and the cytotoxic
      studies were performed using LND-CS-NPs. This study implies the new drug delivery
      route for lenalidomide and illustrates that the CS-NPs serves as the effective
      pharmaceutical carrier for sustained delivery of lenalidomide.

PMID- 24742717
TI  - Standing versus supine radiographs to evaluate femoral head penetration in the
      polyethylene liner after total hip arthroplasty.
AB  - The linear penetration rates for ceramic femoral heads on conventional and highly
      cross-linked polyethylene were measured and compared with radiographs taken in
      the standing and supine position taken three weeks postoperatively and at final
      follow-up. Seventy-five patients (83 hips) with conventional polyethylene (group
      1) and two hundred and seventy five patients (300 hips) with highly cross-linked
      polyethylene (group-2) were studied. Follow-up periods were 14.5years in group-1
      and 8.6years in group-2. The average penetration rates in group-1 were
      0.17mm/year in supine position and 0.18mm/year in standing position (P<0.05). On
      the other hand, the rates in group-2 were 0.03mm/year and 0.04mm/year
      respectively (P<0.05). Although there were statistical differences between
      groups, 0.01mm differences are probably not clinically relevant.

PMID- 24742718
TI  - Recognition of emotional facial expressions and broad autism phenotype in parents
      of children diagnosed with autistic spectrum disorder.
AB  - OBJECTIVE: Research findings debate about features of broad autism phenotype. In
      this study, we tested whether parents of children with autism have problems
      recognizing emotional facial expression and the contribution of such an
      impairment to the broad phenotype of autism. METHOD: Seventy-two parents of
      children with autistic spectrum disorder and 38 parents of control group
      participated in the study. Broad autism features was measured with Autism
      Quotient (AQ). Recognition of Emotional Face Expression Test was assessed with
      the Emotion Recognition Test, consisting a set of photographs from Ekman &
      Friesen's. RESULTS: In a two-tailed analysis of variance of AQ, there was a
      significant difference for social skills (F(1, 106)=6.095; p<.05). Analyses of
      variance revealed significant difference in the recognition of happy, surprised
      and neutral expressions (F(1, 106)=4.068, p=.046; F(1, 106)=4.068, p=.046; F(1,
      106)=6.064, p=.016). CONCLUSION: According to our findings, social impairment
      could be considered a characteristic feature of BAP. ASD parents had difficulty
      recognizing neutral expressions, suggesting that ASD parents may have impaired
      recognition of ambiguous expressions as do autistic children.

PMID- 24742719
TI  - Parents of adolescents with psychiatric disorders: insight into the disorder,
      self-stigma and parental stress.
AB  - BACKGROUND: Parents of adolescents with mental disorders experience stress
      partially due to the way they perceive and experience their offspring's disorder.
      The current study assessed the mediator role of self-stigma in the relationship
      between insight into the disorder and parental stress of parents of adolescents
      with mental disorders. METHOD: A total of 37 parents of adolescents with
      psychiatric disorders were assessed for their level of insight, self-stigma and
      parental stress. RESULTS: The hypothesized mediation model was confirmed and is
      consistent with previous study on parents of adults with severe mental illness.
      DISCUSSION: The positive association between insight and parental stress is
      mediated by these parents' self-stigma, suggesting that insight increases the
      self-stigma, which in turn increases the parental stress. These results may have
      clinical implications with regard to the treatment of the family of adolescents
      with mental disorders.

PMID- 24742721
TI  - A persistent organic pollutant related with unusual high frequency of
      hermaphroditism in the neotropical anuran Physalaemus cuvieri Fitzinger, 1826.
AB  - Representing a reflection of anthropic activity, the level of xenobiotic
      compounds in aquatic ecosystems has increased in recent years, bringing severe
      damage to the environment. The present work reports the occurrence of
      malformation in gonads of Physalaemus cuvieri individuals from a population of
      Atlantic Forest in Southern Brazil. Twenty male specimens were collected, which
      had their testicles removed, immersed in Karnovsky fixative solution, included in
      historesin for 2 MUm cuts and stained with Hematoxylin-eosin. Four specimens
      showed intersexual gonads condition along with the presence of sperm and oocytes.
      In order to test a possible contamination of water, 2L were collected from the
      water body to check organochlorine, organophosphate and carbamate compounds. The
      analysis of water showed the presence of agrotoxic Dieldrin in a concentration of
      0.05 MUg/L, representing a concentration above the recommended reference. This
      agrotoxic, in addition to acting as endocrine disrupter and commercially
      prohibited, has quite persistent residual effects, and may be responsible for the
      high frequency of P. cuvieri with intersexual gonads, which in the long term can
      represent a risk for this population due to the potential impact on its effective
      reproductive ability.

PMID- 24742720
TI  - Persistent organochlorines and hypertensive disorders of pregnancy.
AB  - Although there is indirect evidence to suggest that persistent organochlorines
      might increase risk of hypertensive disorders of pregnancy, there are no
      epidemiologic studies directly addressing this question. In this cohort study,
      sampled from the Collaborative Perinatal Project, 1933 women had complete data on
      organochlorine measurements, covariates, and pregnancy outcomes. Exposures to
      organochlorines were divided into quintiles, and levels were much higher in these
      patients recruited from 1959 to 1965 compared to levels in the general population
      at present. Among included women, 364 developed gestational hypertension
      (hypertension without proteinuria) and 131 developed preeclampsia (hypertension
      with proteinuria). We found essentially no association between serum DDE and
      total PCBs and risk of either gestational hypertension or preeclampsia. Results
      for other organochlorines showed varying patterns of results: DDT was inversely
      associated with risk of gestational hypertension (p for trend <0.001), B
      Hexachlorocyclohexane and heptachlor epoxide were inversely related to
      gestational hypertension (p trend <0.01 and 0.10, respectively), dieldrin had a
      modestly positive association with gestational hypertension (p for trend=0.12),
      and hexachlorobenzene, trans-nonachlor, and oxychlordane yielded results close to
      the null. Hexachlorobenzene showed an inverse association with preeclampsia (p
      for trend <0.001). The study suggests that persistent organochlorines present at
      historically high level are not likely to increase the risk of hypertensive
      disorders of pregnancy, suggesting that other toxicants that have similar
      biologic effects are also unlikely to do so. 

PMID- 24742722
TI  - Novel biomarkers of mercury-induced autoimmune dysfunction: a cross-sectional
      study in Amazonian Brazil.
AB  - Mercury is a ubiquitous environmental contaminant, causing both neurotoxicity and
      immunotoxicity. Given its ability to amalgamate gold, mercury is frequently used
      in small-scale artisanal gold mining. We have previously reported that elevated
      serum titers of antinuclear autoantibodies (ANA) are associated with mercury
      exposures of miners in gold mining. The goal of this project was to identify
      novel serum biomarkers of mercury-induced immunotoxicity and autoimmune
      dysregulation. We conducted an analysis of serum samples from a cross-sectional
      epidemiological study on miners working in Amazonian Brazil. In proteomic
      screening analyses, samples were stratified based on mercury concentrations and
      ANA titer and a subset of serum samples (N=12) were profiled using Immune
      Response Biomarker Profiling ProtoArray protein microarray for elevated
      autoantibodies. Of the up-regulated autoantibodies in the mercury-exposed cohort,
      potential target autoantibodies were selected based on relevance to pro
      inflammatory and macrophage activation pathways. ELISAs were developed to test
      the entire sample cohort (N=371) for serum titers to the highest of these
      autoantibodies (anti-glutathione S-transferase alpha, GSTA1) identified in the
      high mercury/high ANA group. We found positive associations between elevated
      mercury exposure and up-regulated serum titers of 3760 autoantibodies as
      identified by ProtoArray. Autoantibodies identified as potential novel biomarkers
      of mercury-induced immunotoxicity include antibodies to the following proteins:
      GSTA1, tumor necrosis factor ligand superfamily member 13, linker for activation
      of T cells, signal peptide peptidase like 2B, stimulated by retinoic acid 13, and
      interferon induced transmembrane protein. ELISA analyses confirmed that mercury
      exposed gold miners had significantly higher serum titers of anti-GSTA1
      autoantibody [unadjusted odds ratio=89.6; 95% confidence interval: 27.2, 294.6]
      compared to emerald miners (referent population). Mercury exposure was associated
      with increased titers of several autoantibodies in serum including anti-GSTA1.
      These proteins play a wide variety of roles, including as antioxidants, in the
      regulation of pro- and anti-inflammatory cytokines, as well as danger and
      oxidative stress signaling. Dysregulation of these proteins and pathways is
      believed to play a role in autoimmune diseases such as rheumatoid arthritis,
      Sjogren's syndrome, and multiple sclerosis. Taken together, these results suggest
      that mercury exposure can induce complex autoimmune dysfunction and the
      immunotoxic effects of this dysfunction may be measured by serum titers to
      autoantibodies such as anti-GSTA1. 

PMID- 24742723
TI  - Prenatal exposure to p,p'-DDE and p,p'-DDT in relation to lower respiratory tract
      infections in boys from a highly exposed area of Mexico.
AB  - BACKGROUND: Prenatal exposure to 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene
      (p,p'-DDE), the major breakdown product of DDT, has been associated with
      recurrent lower respiratory tract infections (LRTIs) in infants. However,
      epidemiological investigations are limited. OBJECTIVE: To assess the association
      of prenatal exposure to p,p'-DDE and p,p'-DDT with the occurrence of LRTI in boys
      from Chiapas, a highly exposed area of Mexico. METHODS: We analyzed data from 747
      singleton boys whose prenatal exposure to p,p'-DDE and p,p'-DDT was determined in
      maternal serum drawn at delivery (2002-2003). LRTI (i.e., pneumonia,
      bronchiolitis, and other illness of the bronchi) experienced by the children were
      reported by their mothers during in-person interviews. The median age of the
      children when they were last seen was 21.4 months (quartiles 19.1 and 25.3
      months). RESULTS: Median exposure to p,p'-DDE in this population was higher (2.7
      ug/g lipid) than recent U.S. levels (0.20 ug/g). There were 0.19 episodes of LRTI
      per child-year. After adjusting for potential confounders, children in the
      highest category of p,p'-DDE (>9.00 ug/g) exposure compared to those in the
      lowest (<= 3.00 ug/g) had an adjusted incidence rate ratio (aIRR) of LRTI of 0.77
      (95% confidence interval [CI], 0.41-1.46). The corresponding aIRR for p,p'-DDT
      (>= 2.00 ug/g compared to <= 0.25 ug/g) was 0.65 (95% CI: 0.30-1.39). CONCLUSION:
      An association of prenatal exposure to p,p'-DDE and p,p'-DDT with LRTI during
      childhood was not supported in this population with relatively high levels of
      exposure.

PMID- 24742724
TI  - Prenatal exposure to environmental contaminants and body composition at age 7-9
      years.
AB  - The study aim was to investigate the association between prenatal exposure to
      endocrine disrupting chemicals (EDCs) and the body composition of 7 to 9 year old
      Flemish children. The subjects were 114 Flemish children (50% boys) that took
      part in the first Flemish Environment and Health Study (2002-2006). Cadmium,
      PCBs, dioxins, p,p'-DDE and HCB were analysed in cord blood/plasma. When the
      child reached 7-9 years, height, weight, waist circumference and skinfolds were
      measured. Significant associations between prenatal exposure to EDCs and
      indicators of body composition were only found in girls. After adjustment for
      confounders and covariates, a significant negative association was found in girls
      between prenatal cadmium exposure and weight, BMI and waist circumference
      (indicator of abdominal fat) and the sum of four skinfolds (indicator of
      subcutaneous fat). In contrast, a significant positive association (after
      adjustment for confounders/covariates) was found between prenatal p,p'-DDE
      exposure and waist circumference as well as waist/height ratio in girls
      (indicators of abdominal fat). No significant associations were found for
      prenatal PCBs, dioxins and HCB exposure after adjustment for
      confounders/covariates. This study suggests a positive association between
      prenatal p,p'-DDE exposure and indicators of abdominal fat and a negative
      association between prenatal cadmium exposure and indicators of both abdominal as
      well as subcutaneous fat in girls between 7 and 9 years old. 

PMID- 24742725
TI  - Leisure time activities related to carcinogen exposure and lung cancer risk in
      never smokers. A case-control study.
AB  - We aim to assess the relationship between leisure time activities related to
      exposure to carcinogenic substances and lung cancer risk in a hospital-based case
      control study performed in never smokers. We included never smoking cases with
      anatomopathologically confirmed lung cancer and never smoking controls undergoing
      trivial surgery, at 8 Spanish hospitals. The study was conducted between January
      2011 and June 2013. Participants were older than 30 and had no previous
      neoplasms. All were personally interviewed focusing on lifestyle, environmental
      tobacco smoke exposure, occupational history and leisure time activities
      (including duration of such activities). Results were analyzed through logistic
      regression and adjusted also by residential radon and education level. We
      included 513 never smokers, 191 cases and 322 controls. The OR for those
      performing the studied leisure time activities was 1.43 (95%CI 0.78-2.61). When
      we restricted the analysis to those performing do-it-yourself activities for more
      than 10 years the OR was 2.21 (95%CI 0.93-5.27). Environmental tobacco smoke
      exposure did not modify this association. The effect for the different lung
      cancer histological types was very close to significance for adenocarcinoma but
      only when these activities were performed for more than 10 years. We encourage
      health professionals to recommend protective measures for those individuals while
      performing these hobbies to reduce the risk of lung cancer. 

PMID- 24742726
TI  - Associations between personal exposure to air pollutants and lung function tests
      and cardiovascular indices among children with asthma living near an industrial
      complex and petroleum refineries.
AB  - OBJECTIVE: The acute cardiorespiratory effects of air quality among children
      living in areas with considerable heavy industry have not been well investigated.
      We conducted a panel study of children with asthma living in proximity to an
      industrial complex housing two refineries in Montreal, Quebec, in order to assess
      associations between their personal daily exposure to air pollutants and changes
      in pulmonary function and selected indicators of cardiovascular health. METHODS:
      Seventy-two children with asthma age 7-12 years in 2009-2010 participated in this
      panel study for a period of 10 consecutive days. They carried a small backpack
      for personal monitoring of sulphur dioxide (SO2), benzene, fine particles
      (PM2.5), nitrogen dioxide (NO2) and polycyclic aromatic hydrocarbons (PAHs) and
      underwent daily spirometry and cardiovascular testing (blood pressure, pulse rate
      and oxygen saturation). To estimate these associations, we used mixed regression
      models, adjusting for within-subject serial correlation, and for the effects of a
      number of personal and environmental variables (e.g., medication use, ethnicity,
      temperature). RESULTS: Children with asthma involved in the study had relatively
      good pulmonary function test results (mean FEV1 compared to standard values:
      89.8%, mean FVC: 97.6%, mean FEF25-75: 76.3%). Median diastolic, systolic blood
      pressures and oxygen saturation were 60/94 mmHg and 99%, respectively. Median
      personal concentrations of pollutants were NO2, 5.5 ppb; benzene, 2.1 ug/m(3);
      PM2.5, 5.7 ug/m(3); and total PAH, 130 ug/m(3). Most personal concentrations of
      SO2 were below the level of detection. No consistent associations were observed
      between cardio-pulmonary indices and personal exposure to PM2.5, NO2 and benzene,
      although there was a suggestion for a small decrease in respiratory function with
      total concentrations of PAHs (e.g., adjusted association with FVC: -9.9 ml per
      interquartile range 95%CI: -23.4, 3.7). CONCLUSIONS: This study suggests that at
      low daily average levels of exposure to industrial emissions, effects on
      pulmonary and cardiovascular functions in children with asthma may be difficult
      to detect over 10 consecutive days.

PMID- 24742727
TI  - Indoor particulate reactive oxygen species concentrations.
AB  - Despite the fact that precursors to reactive oxygen species (ROS) are prevalent
      indoors, the concentration of ROS inside buildings is unknown. ROS on PM2.5 was
      measured inside and outside twelve residential buildings and eleven institutional
      and retail buildings. The mean (+/- s.d.) concentration of ROS on PM2.5 inside
      homes (1.37 +/- 1.2 nmoles/m(3)) was not significantly different from the outdoor
      concentration (1.41 +/- 1.0 nmoles/m(3)). Similarly, the indoor and outdoor
      concentrations of ROS on PM2.5 at institutional buildings (1.16 +/- 0.38
      nmoles/m(3) indoors and 1.68 +/- 1.3 nmoles/m(3) outdoors) and retail stores
      (1.09 +/- 0.93 nmoles/m(3) indoors and 1.12 +/- 1.1 nmoles/m(3) outdoors) were
      not significantly different and were comparable to those in residential
      buildings. The indoor concentration of particulate ROS cannot be predicted based
      on the measurement of other common indoor pollutants, indicating that it is
      important to separately assess the concentration of particulate ROS in air
      quality studies. Daytime indoor occupational and residential exposure to
      particulate ROS dominates daytime outdoor exposure to particulate ROS. These
      findings highlight the need for further study of ROS in indoor microenvironments.

PMID- 24742728
TI  - Impairment of uterine smooth muscle contractions and prostaglandin secretion from
      cattle myometrium and corpus luteum in vitro is influenced by DDT, DDE and HCH.
AB  - The aim of this study was to investigate the effect of
      dichlorodiphenyltrichloroethane(DDT), dichlorodiphenyldichloroethylene (DDE) and
      gamma-hexachlorocyclohexane (HCH) (10 ng/ml) on myometrial motility and the
      secretory function of the myometrium and corpus luteum (CL) collected from cows
      on days 8-12 of the estrous cycle. All of the xenobiotics increased (P<0.05)
      myometrial contractility. Moreover, the xenobiotics stimulated the secretion of
      the following prostaglandins (PGs) from myometrial strips: PGF2alpha, PGE2 and
      PGI2. DDT and DDE also increased (P<0.05) the release of PGF2alpha from CL
      strips, and HCH had the same effect (P<0.05) on the secretion of PGE2 and PGI2.
      The studied xenobiotics did not affect (P>0.05) PG synthesis, but DDT and DDE
      increased the mRNA expression levels of leukemia inhibitor factor (LIF), which
      can stimulate PG production. In summary, the xenobiotics affected PG secretion
      from cow myometrium and CL, which may contribute to the mechanism of uterine
      contraction disturbance.

PMID- 24742729
TI  - Early life perfluorooctanoic acid (PFOA) exposure and overweight and obesity risk
      in adulthood in a community with elevated exposure.
AB  - BACKGROUND: Infants and young children may be susceptible to developmental
      effects of perfluorooctanoic acid (PFOA) exposure. Two previous studies, one that
      examined a general population exposed to environmental PFOA levels and one
      conducted in mice exposed to experimental PFOA levels, found that early life
      exposure was associated with higher body mass index (BMI) in adulthood and
      effects may be stronger in women than in men. OBJECTIVES: Examine whether
      elevated early life PFOA exposure was associated with adult BMI among a group of
      mid-Ohio valley residents exposed to a wide range of early life PFOA levels due
      to emissions from a chemical plant. METHODS: The cohort consisted of 8764 adults
      aged 20-40 years who reported height and weight on a survey between 2008 and
      2011. Annual retrospective early life PFOA serum concentrations were estimated
      for each participant based on residential history and nearby chemical plant
      emissions as well as background exposure not originating from the facility. We
      defined early life exposure as the estimated average PFOA serum concentration
      over the first three years of life. We examined the association between early
      life PFOA exposure and adult overweight (BMI >= 25 kg/m(2)) and obesity (BMI >=
      30 kg/m(2)) risk using logistic and linear regression models. RESULTS: Nearly
      half the participants (45%) had early life PFOA exposure serum concentration
      estimates above background levels. Using participants who were exposed only to
      background PFOA levels as the referent category with quintiles of exposure above
      background, adjusted odds ratios (and 95% confidence intervals) for overweight
      risk by increasing exposure category for women were 1.0 (ref), 1.0 (0.8, 1.3),
      1.0 (0.8, 1.2), 1.0 (0.8, 1.2), 0.9 (0.7, 1.1), and 0.9 (0.7, 1.1) and for men
      were 1.0 (ref), 0.9 (0.6, 1.1), 1.0 (0.7, 1.3), 1.0 (0.8, 1.4), 0.7 (0.5, 0.9),
      and 0.9 (0.7, 1.1). Odds ratios for adult obesity risk were similar. Regression
      coefficients from linear models using BMI as a continuous outcome showed no
      association between early life PFOA exposure and adult BMI. CONCLUSIONS: Elevated
      levels of PFOA exposure in early life were not associated with overweight and
      obesity risk in adulthood and results did not vary by sex.

PMID- 24742730
TI  - Lead in new paints in Nepal.
AB  - Samples from 75 paint products made by 21 domestic and foreign manufacturers were
      purchased from retail stores in five major cities in Nepal and tested for lead
      content. Information provided on product labels were noted. Samples were selected
      to be representative of the large number of brands and colors available in retail
      shops. Although a majority of the products purchased were manufactured in Nepal,
      paints from four additional countries were tested. Out of a total of 75 samples,
      57 (76%) of the tested paints contained lead at concentrations greater than 90
      ppm (ppm). Ninety-three percent of the paints that exceeded 90 ppm had levels in
      excess of 600 ppm. Lead concentrations in the tested paints ranged up to 200,000
      ppm (20%) lead by weight and the median concentration was 5100 ppm. These results
      indicate that lead paint is commonly being sold for residential and other
      consumer applications in Nepal without any consumer warnings. Regulations are
      needed to specify the maximum concentration of lead allowed in paint products
      manufactured, imported, or distributed in the country to protect public health.
      Efforts must be made to get lead-containing paint products recalled from stores
      so that they are not used in homes, schools, and other child-occupied facilities.

PMID- 24742731
TI  - Extracellular histones mediate the effects of metal-rich air particles on blood
      coagulation.
AB  - BACKGROUND: Epidemiological studies have shown associations of particulate matter
      (PM) exposure with hypercoagulability and thrombosis. Extracellular circulating
      histones have recently been identified as novel mediators of inflammatory and
      procoagulant responses. The potential roles of extracellular histones in PM
      related hypercoagulability have yet not been investigated. OBJECTIVES: In 63
      steel workers, we evaluated the effects of exposure to PM and PM metal components
      on two extracellular histone modifications (H3K4me3 and H3K9ac); and the
      association of H3K4me3 and H3K9ac with coagulation markers. METHODS:
      Extracellular H3K4me3 and H3K9ac were determined in plasma through enzyme-linked
      immunosorbent assays. Coagulation markers included endogenous thrombin potentials
      (ETPs), tissue-type plasminogen activator antigen (t-PA) and D-dimer. Exposure to
      PM with aerodynamic diameters <1 MUm (PM1) or <10 MUm (PM10) and PM10 metal
      components were estimated for each participant. RESULTS: The coagulation marker
      ETP, measured in the presence of soluble thrombomodulin (ETP TM+), showed
      significant positive associations with PM1 (beta=107.84, p=0.03), PM10
      (beta=83.06, p=0.02), and zinc (beta=75.14, p=0.03); and a marginal association
      with iron (beta=122.58, p=0.07). Additional PM effects were observed on t-PA, D
      dimer, and ETP TM+. PM1 exposure was associated with increased plasma H3K4me3 and
      H3K9ac (beta=0.20, p=0.02; beta=0.16, p=0.05, respectively). H3K4me3, but not
      H3K9ac, was associated with zinc (beta=0.13, p=0.03) and iron (beta=0.32, p=0.01)
      contained in PM. ETP TM+ was increased in association with higher plasma H3K4me3
      (beta=0.50, p=0.05) and H3K9ac (beta=0.54, p=0.05). CONCLUSIONS: This
      observational study suggests potential roles of extracellular histones in PM
      induced hypercoagulability. Experimental studies are warranted to further
      characterize these findings.

PMID- 24742733
TI  - Ordering and interpreting hepatitis B serology.

PMID- 24742734
TI  - Selecting an internationally diverse medical workforce.

PMID- 24742735
TI  - New tools and approaches for improved management of inflammatory bowel diseases.
AB  - BACKGROUND AND AIMS: Inflammatory bowel diseases are part of a wider
      conglomeration of immune-mediated inflammatory diseases. New management
      approaches need to be developed as we understand more of the epidemiology and
      aetiology of inflammatory bowel diseases and medical care becomes more complex.
      METHODS: Selected new tools and approaches for improved management of
      inflammatory bowel diseases are presented, based on published evidence and
      clinical experience. RESULTS: Setting quality of care standards that are
      consistent across different inflammatory bowel disease care settings will be
      paramount and require collaboration between specialist and non-specialist
      centres. Alongside this, the value of care will need to be evaluated in terms of
      maximising outcomes over the entire care cycle for a patient. In moving towards a
      value-based approach to management, it is important to determine the progression
      rate of the disease by measuring cumulative bowel damage. As well as
      understanding the course of disease in individual patients, it is also becoming
      more feasible to individualise therapy and exploit drug pharmacology to achieve
      better and more long-term responses. Finally, it is timely to consider formal
      collaborations between specialists in immune-mediated inflammatory diseases to
      ensure more cohesive patient care. CONCLUSIONS: The potential for improved
      management of patients with inflammatory bowel diseases continues to increase as
      we look to understand when and how to intervene in the disease process and how to
      adopt a collaborative management approach that promotes networking and reduces
      heterogeneity of care across different care settings.

PMID- 24742736
TI  - Future directions in inflammatory bowel disease management.
AB  - BACKGROUND AND AIMS: Clinical management of inflammatory bowel diseases (IBD),
      new treatment modalities and the potential impact of personalised medicine remain
      topics of intense interest as our understanding of the pathophysiology of IBD
      expands. METHODS: Potential future strategies for IBD management are discussed,
      based on recent preclinical and clinical research. RESULTS: A top-down approach
      to medical therapy is increasingly being adopted for patients with risk factors
      for severe inflammation or an unfavourable disease course in an attempt to halt
      the inflammatory process as early as possible, prevent complications and induce
      mucosal healing. In the future, biological therapies for IBD are likely to be
      used more selectively based on personalised benefit/risk assessment, determined
      through reliable biomarkers and tissue signatures, and will probably be optimised
      throughout the course of treatment. Biologics with different mechanisms of action
      will be available; when one drug fails, patients will be able to switch to
      another and even combination biologics may become a reality. The role of
      biotherapeutic products that are similar to currently licensed biologics in terms
      of quality, safety and efficacy - i.e. biosimilars - is at an early stage and
      requires further experience. Other therapeutic strategies may involve
      manipulation of the microbiome using antibiotics, probiotics, prebiotics, diet
      and combinations of all these approaches. Faecal microbiota transplantation is
      also a potential option in IBD although controlled data are lacking. CONCLUSIONS:
      The future of classifying, prognosticating and managing IBD involves an outcomes
      based approach to identify biomarkers reflecting various biological processes
      that can be matched with clinically important endpoints.

PMID- 24742737
TI  - The stability of iso-alpha-acids and reduced iso-alpha-acids in stored blood
      specimens.
AB  - The long-term stability of the iso-alpha-acids, and three structurally similar
      but chemically altered iso-alpha-acids (known as 'reduced iso-alpha-acids' and
      consisting of the rho-, tetrahydro- and hexahydro-iso-alpha-acid groups) were
      investigated in whole blood. Pools of blank blood spiked with the four beer
      specific ingredient congener groups at two different concentration levels were
      stored at 20 degrees C, 4 degrees C and -20 degrees C; and extracted in duplicate
      in weeks 1, 3, 5 and 8, using a previously published method. A loss of 15% of the
      initial concentration was considered to indicate possible instability and losses
      greater than 30% demonstrated significant losses. The individual analytes within
      the four iso-alpha-acid groups were also measured to determine which iso-alpha
      acids were subject to greater degradation and were responsible for the overall
      group instability. All four iso-alpha-acid groups showed significant losses after
      8 weeks of storage under room temperature conditions in particularly the natural
      iso-alpha-acid group where major losses were observed (96% and 85% losses for low
      and high concentrations, respectively). Some degradation in all iso-alpha-acid
      groups were seen at 4 degrees C samples predominantly due to the 'n' analogs of
      the groups showing an increased instability in blood. The -20 degrees C storage
      conditions resulted in minimal changes in concentrations of all analytes. Higher
      than frozen storage temperatures can result in substantial changes on the
      stability of the iso-alpha-acid type groups in blood. The aim of this study was
      to highlight the stabilities of the IAA analytes in order to assist in the
      interpretation of IAA in stored blood specimens. 

PMID- 24742738
TI  - Irradiation stents: a clever, and maybe costly, fusion.

PMID- 24742739
TI  - Everolimus for women with trastuzumab-resistant, HER2-positive, advanced breast
      cancer (BOLERO-3): a randomised, double-blind, placebo-controlled phase 3 trial.
AB  - BACKGROUND: Disease progression in patients with HER2-positive breast cancer
      receiving trastuzumab might be associated with activation of the PI3K/Akt/mTOR
      intracellular signalling pathway. We aimed to assess whether the addition of the
      mTOR inhibitor everolimus to trastuzumab might restore sensitivity to
      trastuzumab. METHODS: In this randomised, double-blind, placebo-controlled, phase
      3 trial, we recruited women with HER2-positive, trastuzumab-resistant, advanced
      breast carcinoma who had previously received taxane therapy. Eligible patients
      were randomly assigned (1:1) using a central patient screening and randomisation
      system to daily everolimus (5 mg/day) plus weekly trastuzumab (2 mg/kg) and
      vinorelbine (25 mg/m(2)) or to placebo plus trastuzumab plus vinorelbine, in 3
      week cycles, stratified by previous lapatinib use. The primary endpoint was
      progression-free survival (PFS) by local assessment in the intention-to-treat
      population. We report the final analysis for PFS; overall survival follow-up is
      still in progress. This trial is registered with ClinicalTrials.gov, number
      NCT01007942. FINDINGS: Between Oct 26, 2009, and May 23, 2012, 569 patients were
      randomly assigned to everolimus (n=284) or placebo (n=285). Median follow-up at
      the time of analysis was 20.2 months (IQR 15.0-27.1). Median PFS was 7.00 months
      (95% CI 6.74-8.18) with everolimus and 5.78 months (5.49-6.90) with placebo
      (hazard ratio 0.78 [95% CI 0.65-0.95]; p=0.0067). The most common grade 3-4
      adverse events were neutropenia (204 [73%] of 280 patients in the everolimus
      group vs 175 [62%] of 282 patients in the placebo group), leucopenia (106 [38%]
      vs 82 [29%]), anaemia (53 [19%] vs 17 [6%]), febrile neutropenia (44 [16%] vs ten
      [4%]), stomatitis (37 [13%] vs four [1%]), and fatigue (34 [12%] vs 11 [4%]).
      Serious adverse events were reported in 117 (42%) patients in the everolimus
      group and 55 (20%) in the placebo group; two on-treatment deaths due to adverse
      events occurred in each group. INTERPRETATION: The addition of everolimus to
      trastuzumab plus vinorelbine significantly prolongs PFS in patients with
      trastuzumab-resistant and taxane-pretreated, HER2-positive, advanced breast
      cancer. The clinical benefit should be considered in the context of the adverse
      event profile in this population.

PMID- 24742741
TI  - The why, what, how and where of 3D imaging.

PMID- 24742740
TI  - Conventional stents versus stents loaded with (125)iodine seeds for the treatment
      of unresectable oesophageal cancer: a multicentre, randomised phase 3 trial.
AB  - BACKGROUND: The combination of stent insertion and single high-dose brachytherapy
      is a feasible and safe palliative treatment regimen in patients with unresectable
      oesophageal cancer. We aimed to further assess the efficacy of this treatment
      strategy compared to a conventional covered stent in patients with dysphagia
      caused by unresectable oesophageal cancer. METHODS: In this multicentre, single
      blind, randomised, phase 3 trial, we enrolled patients with unresectable
      oesophageal cancer from 16 hospitals in China. We included adult patients (aged
      >= 20 years) with progressive dysphagia, unresectable tumours due to extensive
      lesions, metastases, or poor medical condition, and with clear consciousness,
      cooperation, and an Eastern Cooperative Oncology Group (ECOG) performance status
      score of 0-3. Eligible patients were randomly assigned (in 1:1 ratio, no
      stratification) to receive either a stent loaded with (125)iodine radioactive
      seeds (irradiation group) or a conventional oesophageal stent (control group).
      The primary endpoint was overall survival. Survival analyses were done in a
      modified intention-to-treat group. This study is registered with
      ClinicalTrials.gov, number NCT01054274. FINDINGS: Between Nov 1, 2009, and Oct
      31, 2012, 160 patients were randomly assigned to receive treatment with either an
      irradiation stent (n=80) or a conventional stent (n=80). During a median follow
      up of 138 days (IQR 72-207), 148 stents (73 in the irradiation group and 75 in
      the control group) were successfully placed into the diseased oesophagus in 148
      participants. Median overall survival was 177 days (95% CI 153-201) in the
      irradiation group versus 147 days (124-170) in the control group (p=0.0046).
      Major complications and side-effects of the treatment were severe chest pain (17
      [23%] of 73 patients in the irradiation group vs 15 [20%] of 75 patents in the
      control group), fistula formation (six [8%] vs five [7%]), aspiration pneumonia
      (11 [15%] vs 14 [19%]), haemorrhage (five [7%] vs five [7%]), and recurrent
      dysphagia (21 [28%] vs 20 [27%]). INTERPRETATION: In patients with unresectable
      oesophageal cancer, the insertion of an oesophageal stent loaded with (125)iodine
      seeds prolonged survival when compared with the insertion of a conventional
      covered self-expandable metallic stent.

PMID- 24742742
TI  - Commentary on Farah et al. Secondary displacement of distal radius fractures
      treated by bridging external fixation.

PMID- 24742743
TI  - Re: Becker SJE, Makanji HS and Ring D. Changes in treatment plan for carpal
      tunnel syndrome based on electrodignostic test results. J Hand Surg Eur. 2014,
      39: 187-93.

PMID- 24742744
TI  - Re: Al-Qattan MM. Concurrent dorsal dimelia in 160 consecutive patients with
      congenital anomalies of the hands and feet. J Hand Surg Eur 2013. Epub ahead of
      print 20 December 2013. DOI: 10.1177/1753193413517458.

PMID- 24742745
TI  - Raoul Tubiana 1915 - 2013.

PMID- 24742746
TI  - On oral and cranio-maxillofacial surgery in Byzantium, addenda.

PMID- 24742747
TI  - Comparison of piezosurgery and traditional saw in bimaxillary orthognathic
      surgery.
AB  - PURPOSE: Investigators have hypothesised that piezoelectric surgical device could
      permanently replace traditional saws in conventional orthognathic surgery.
      METHODS: Twelve consecutive patients who underwent bimaxillary procedures were
      involved in the study. In six patients the right maxillary and mandible
      osteotomies were performed using traditional saw, whilst the left osteotomies by
      piezoosteotomy; in the remaining six patients, the surgical procedures were
      reversed. Intraoperative blood loss, procedure duration time, incision precision,
      postoperative swelling and haematoma, and nerve impairment were evaluated to
      compare the outcomes and costs of these two procedures. RESULTS: Compare to
      traditional mechanical surgery, piezoosteotomy showed a significant
      intraoperative blood loss reduction of 25% (p = 0.0367), but the mean surgical
      procedure duration was longer by 35% (p = 0.0018). Moreover, the use of
      piezoosteotomy for mandible procedure required more time than for the maxillary
      surgery (p = 0.0003). There was a lower incidence of postoperative haematoma and
      swelling following piezoosteotomy, and a statistically significant reduction in
      postoperative nerve impairment (p = 0.003). CONCLUSIONS: We believe that
      piezoelectric device allows surgeons to achieve better results compared to a
      traditional surgical saw, especially in terms of intraoperative blood loss,
      postoperative swelling and nerve impairment. This device represents a less
      aggressive and safer method to perform invasive surgical procedures such as a Le
      Fort I osteotomy. However, we recommend the use of traditional saw in mandible
      surgery because it provides more foreseeable outcomes and well-controlled
      osteotomy. Further studies are needed to analyse whether piezoosteotomy could
      prevent relapse and promote bony union in larger advancements.

PMID- 24742748
TI  - Dilution of dipolar interactions in a spin-labeled, multimeric metalloenzyme for
      DEER studies.
AB  - The metallo-beta-lactamases (MbetaLs), which require one or two Zn(II) ions in
      their active sites for activity, hydrolyze the amide bond in beta-lactam
      containing antibiotics, and render the antibiotics inactive. All known MbetaLs
      contain a mobile element near their active sites, and these mobile elements have
      been implicated in the catalytic mechanisms of these enzymes. However little is
      known about the dynamics of these elements. In this study, we prepared a site
      specific, double spin-labeled analog of homotetrameric MbetaL L1 with spin labels
      at positions 163 and 286 and analyzed the sample with DEER (double electron
      electron resonance) spectroscopy. Four unique distances were observed in the DEER
      distance distribution, and these distances were assigned to the desired
      intramolecular dipolar coupling (between spin labels at positions 163 and 286 in
      one subunit) and to intermolecular dipolar couplings. To rid the spin-labeled
      analog of L1 of the intermolecular couplings, spin-labeled L1 was "diluted" by
      unfolding/refolding the spin-labeled enzyme in the presence of excess wild-type
      L1. DEER spectra of the resulting, spin-diluted enzyme revealed a single distance
      corresponding to the desire intramolecular dipolar coupling. 

PMID- 24742749
TI  - Effects of low-intensity pulsed ultrasound on integrin-FAK-PI3K/Akt
      mechanochemical transduction in rabbit osteoarthritis chondrocytes.
AB  - The effect of low-intensity pulsed ultrasound (LIPUS) on extracellular matrix
      (ECM) production via modulation of the integrin/focal adhesion kinase
      (FAK)/phosphatidylinositol 3-kinase (PI3K)/Akt pathway has been investigated in
      previous studies in normal chondrocytes, but not in osteoarthritis (OA).
      Therefore, we investigated the LIPUS-induced integrin beta1/FAK/PI3K/Akt
      mechanochemical transduction pathway in a single study in rabbit OA chondrocytes.
      Normal and OA chondrocytes were exposed to LIPUS, and mRNA and protein expression
      of cartilage, metalloproteinases and integrin-FAK-PI3K/Akt signal pathway-related
      genes was determined by quantitative reverse transcription polymerase chain
      reaction and Western blotting, respectively. Compared with levels in normal
      chondrocytes, expression levels of ECM-related genes were significantly lower in
      OA chondrocytes and those of metalloproteinase-related genes were significantly
      higher. In addition, integrin beta1 gene expression and the phosphorylation of
      FAK, PI3K and Akt were significantly higher in OA chondrocytes. The expression of
      all tested genes was significantly increased except for that of
      metalloproteinase, which was significantly decreased in the LIPUS-treated OA
      group compared to the untreated OA group. LIPUS may affect the integrin-FAK
      PI3K/Akt mechanochemical transduction pathway and alter ECM production by OA
      chondrocytes. Our findings will aid the future development of a treatment or even
      cure for OA.

PMID- 24742750
TI  - Availability of human induced pluripotent stem cell-derived cardiomyocytes in
      assessment of drug potential for QT prolongation.
AB  - Field potential duration (FPD) in human-induced pluripotent stem cell-derived
      cardiomyocytes (hiPS-CMs), which can express QT interval in an electrocardiogram,
      is reported to be a useful tool to predict K(+) channel and Ca(2+) channel
      blocker effects on QT interval. However, there is no report showing that this
      technique can be used to predict multichannel blocker potential for QT
      prolongation. The aim of this study is to show that FPD from MEA (Multielectrode
      array) of hiPS-CMs can detect QT prolongation induced by multichannel blockers.
      hiPS-CMs were seeded onto MEA and FPD was measured for 2min every 10min for 30min
      after drug exposure for the vehicle and each drug concentration. IKr and IKs
      blockers concentration-dependently prolonged corrected FPD (FPDc), whereas Ca(2+)
      channel blockers concentration-dependently shortened FPDc. Also, the multichannel
      blockers Amiodarone, Paroxetine, Terfenadine and Citalopram prolonged FPDc in a
      concentration dependent manner. Finally, the IKr blockers, Terfenadine and
      Citalopram, which are reported to cause Torsade de Pointes (TdP) in clinical
      practice, produced early afterdepolarization (EAD). hiPS-CMs using MEA system and
      FPDc can predict the effects of drug candidates on QT interval. This study also
      shows that this assay can help detect EAD for drugs with TdP potential. 

PMID- 24742751
TI  - Anti-biofilm activity of Marula - a study with the standardized bark extract.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Marula (Sclerocarya birrea; family -
      Anacardiaceae) is an African plant, which enjoys wide socio-economic importance
      particularly in southern part of Africa. The fruits are consumed as food and also
      as alcoholic beverage (cream liquor). In different parts of Africa, the decoction
      of the bark is traditionally used for the treatment of dysentery, diarrhoea, and
      various other infectious conditions. The aim of the study was to investigate the
      anti-biofilm properties of the methanol extract of Marula bark (stem bark of
      Sclerocarya birrea), with a view towards combating the emergence of antimicrobial
      resistance often associated with bacterial biofilms. MATERIALS AND METHODS: The
      standardized methanol extract was initially tested for its antimicrobial
      property. The crystal violet assay was used for evaluating anti-biofilm (biofilm
      formation by Pseudomonas aeuginosa) activity. Further in order to study the
      mechanism of anti-biofilm activity, the same was evaluated for understanding its
      role on various quorums sensing mediated phenomenon (swarming motility assay,
      protease and pyoverdin assay) that are known to be associated with the formation
      of biofilms and pathogenicity. RESULTS: The methanol extract showed no inhibition
      of bacterial growth up to a concentration of 200 ug/ml. Interestingly, the sample
      produced anti-biofilm activity (around 75% decrease; 100 ug/ml) at sub-lethal
      concentration. Further it also significantly reduced the QS mediated swarming
      motility. The release of various virulent factors (protease and pyoverdin) was
      found to be lowered when pre-treated with the extract. CONCLUSION: The present
      study illustrates the anti-biofilm property Sclerocarya birrea. The standardized
      extract significantly disrupted the quorum sensing mediated production of biofilm
      formation and also inhibited swarming ability of the cells. The extract displayed
      a regulatory role on the secretion of protease and pyoverdin, two QS dependent
      pathogenic factors found in Pseudomonas aeruginosa. This study also validates the
      ethnobotanical use of Marula.

PMID- 24742752
TI  - Protective effects of bajijiasu in a rat model of Abeta25-35-induced
      neurotoxicity.
AB  - ETHNOPHARMACOLOGICAL RELEVENCE: Neurodegenerative diseases (NDs) caused by
      neurons and/or myelin loss lead to devastating effects on patients' lives.
      Although the causes of such complex diseases have not yet been fully elucidated,
      oxidative stress, mitochondrial and energy metabolism dysfunction,
      excitotoxicity, inflammation, and apoptosis have been recognized as influential
      factors. Current therapies that were designed to address only a single target are
      unable to mitigate or prevent disease progression, and disease-modifying drugs
      are desperately needed, and Chinese herbs will be a good choice for screening the
      potential drugs. Previous studies have shown that bajijiasu, a dimeric fructose
      isolated from Morinda officinalis radix which was used frequently as a tonifying
      and replenishing natural herb medicine in traditional Chinese medicine clinic
      practice, can prevent ischemia-induced neuronal damage or death. MATERIALS AND
      METHODS: In order to investigate whether bajijiasu protects against beta-amyloid
      (Abeta25-35)-induced neurotoxicity in rats and explore the underlying mechanisms
      of bajijiasu in vivo, we prepared an Alzheimer's disease (AD) model by injecting
      Abeta25-35 into the bilateral CA1 region of rat hippocampus and treated a subset
      with oral bajijiasu. We observed the effects on learning and memory, antioxidant
      levels, energy metabolism, neurotransmitter levels, and neuronal apoptosis.
      RESULTS: Bajijiasu ameliorated Abeta-induced learning and memory dysfunction,
      enhanced antioxidative activity and energy metabolism, and attenuated cholinergic
      system damage. Our findings suggest that bajijiasu can enhance antioxidant
      capacity and prevent free radical damage. It can also enhance energy metabolism
      and monoamine neurotransmitter levels and inhibit neuronal apoptosis. CONCLUSION:
      The results provide a scientific foundation for the use of Morinda officinalis
      and its constituents in the treatment of various AD. Future studies will assess
      the multi-target activity of the drug for the treatment of AD.

PMID- 24742753
TI  - Anti-trypanosomal activity of African medicinal plants: a review update.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: African trypanosomiasis is one of the neglected
      tropical diseases caused by different species of trypanosomes that affect both
      human and livestock with devastating consequences in the continent. Most of the
      affected populations commonly use traditional medicinal plants for the treatment
      of the disease. Consequently, this prompted ethnopharmacological research
      activities on the anti-trypanosomal activity of a number of these African
      medicinal plants in order to validate their ethnomedicinal use. Furthermore, such
      studies could lead to the identification of chemical leads for the development of
      newer anti-trypanosomal agents from those plants. This review aims to provide
      updated information on the ethnopharmacological evidence of African medicinal
      plants with anti-trypanosomal activity. METHODS: Literature was collected via
      electronic search (PubMed, Sciencedirect, Medline and Google Scholar) from
      published articles that report on the in vitro or in vivo anti-trypanosomal
      activity of plants that were collected from different parts of Africa. RESULTS:
      African medicinal plants investigated for in vitro and in vivo anti-trypanosomal
      activity from January 1993 to October 2013 are systematically compiled and all
      the in vivo studies are critically discussed. A total of 264 plant species
      belonging to 79 families were investigated for anti-trypanosomal activity.
      However, only 48 bioactive anti-trypanosomal compounds were successfully isolated
      in pure forms. Furthermore, some of the plants were investigated for possible
      ameliorative effects on the trypanosome-induced pathological changes out of which
      18 plants were reported to be effective while a few others were not. In spite of
      interesting preclinical ethnopharmacological evidence for anti-trypanosomal
      activity, not a single African medicinal plant was investigated in a clinical
      study. CONCLUSION: Several African medicinal plants have demonstrated promising
      anti-trypanosomal effects but the studies on the anti-trypanosomal potentials of
      these plants are not taken beyond proof of concept stage. It is hoped that the
      article would stimulate future clinical studies because of the paucity of
      knowledge in this area.

PMID- 24742754
TI  - Medicinal plants of the Russian Pharmacopoeia; their history and applications.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Due to the location of Russia between West and
      East, Russian phytotherapy has accumulated and adopted approaches that originated
      in European and Asian traditional medicine. Phytotherapy is an official and
      separate branch of medicine in Russia; thus, herbal medicinal preparations are
      considered official medicaments. The aim of the present review is to summarize
      and critically appraise data concerning plants used in Russian medicine. This
      review describes the history of herbal medicine in Russia, the current situation
      and the pharmacological effects of specific plants in the Russian Pharmacopoeia
      that are not included in the European Pharmacopoeia. MATERIALS AND METHODS: Based
      on the State Pharmacopoeia of the USSR (11(th) edition), we selected plant
      species that have not yet been adopted in Western and Central Europe (e.g.,
      selected for inclusion in the European Pharmacopoeia) and systematically searched
      the scientific literature for data using library catalogs, the online service E
      library.ru, and databases such as Medline/Pubmed, Scopus, and the Web of Science
      regarding species, effectiveness, pharmacological effects, and safety. RESULTS:
      The Russian Federation follows the State Pharmacopoeia of the USSR (11(th)
      edition), which contains 83 individual plant monographs. Fifty-one of these
      plants are also found in the European Pharmacopoeia and have been well studied,
      but 32 plants are found only in the Pharmacopoeia of the USSR. Many articles
      about these medicinal plants were never translated in English, and much of the
      information collected by Russian scientists has never been made available to the
      international community. Such knowledge can be applied in future studies aimed at
      a safe, evidence-based use of traditional Russian medicinal plants in European
      and global phytopharmacotherapy as well as for the discovery of novel leads for
      drug development. CONCLUSION: The review highlights the therapeutic potential of
      these Russian phytopharmaceuticals but also highlights cases where concern has
      been raised about product safety and tolerability, which would aid in supporting
      their safe use.

PMID- 24742755
TI  - Adaptive and maladaptive emotion regulation strategies: interactive effects
      during CBT for social anxiety disorder.
AB  - There has been a increasing interest in understanding emotion regulation deficits
      in social anxiety disorder (SAD; e.g., Hofmann, Sawyer, Fang, & Asnaani, 2012).
      However, much remains to be understood about the patterns of associations among
      regulation strategies in the repertoire. Doing so is important in light of the
      growing recognition that people's ability to flexibly implement strategies is
      associated with better mental health (e.g., Kashdan et al., 2014). Based on
      previous work (Aldao & Nolen-Hoeksema, 2012), we examined whether putatively
      adaptive and maladaptive emotion regulation strategies interacted with each other
      in the prediction of social anxiety symptoms in a sample of 71 participants
      undergoing CBT for SAD. We found that strategies interacted with each other and
      that this interaction was qualified by a three-way interaction with a contextual
      factor, namely treatment study phase. Consequently, these findings underscore the
      importance of modeling contextual factors when seeking to understand emotion
      regulation deficits in SAD. 

PMID- 24742756
TI  - The surgeon and self-harm: at the cutting edge.
AB  - Surgeons frequently treat the consequences of self-harm. Self-harm is a common
      problem and presentations to Irish hospitals are increasing. It increases the
      risk of suicide and is associated with long term morbidity. Appropriate
      management can improve the prognosis. Surgeons require a number of skills to
      appropriately manage patients who self-harm. In this review we outline those
      skills including diagnosis, communication, capacity and risk assessment. 

PMID- 24742757
TI  - Surgical resilience: a review of resilience biomarkers and surgical recovery.
AB  - BACKGROUND: Two distinct and large bodies of literature exist on resilience that
      are of potential interest for surgical outcomes. First is the literature on the
      impact of resilience on surgical recovery and wound-healing. Second is the
      literature on biomarkers for resilience, which largely focuses on neuropeptide Y
      (NPY), testosterone and dehydroepiandrosterone (DHEA). Despite this activity,
      there is a dearth of literature linking these two bodies of research by
      investigating biomarkers for surgical resilience and its impact on surgical
      recovery. This paper reviews both bodies of literature within the context of
      surgical recovery. METHOD: Literature searches within Medline and Embase were
      conducted for studies and previous reviews of resilience biomarkers and for the
      impact of individual resilience on surgical recovery. Reference lists of the
      reviews were searched for additional papers. No systematic review is yet possible
      due to the novelty of the use of resilience biomarkers within a surgical context.
      RESULTS: This is the first review to explore a potential link between resilience
      biomarkers and surgical recovery. There are a number of biomarkers that correlate
      with individual resilience levels and resilient individuals exhibit better
      recovery trajectories following surgery, suggesting a novel use of such
      biomarkers for the identification of "surgical resilience". CONCLUSION: By
      identifying surgical resilience, there is potential for utilising these
      biomarkers as prognostic indicators of likely recovery trajectories from surgery,
      which in turn complement individualised peri-operative management.

PMID- 24742758
TI  - The impact of state medical marijuana legislation on adolescent marijuana use.
AB  - PURPOSE: The state-level legalization of medical marijuana has raised concerns
      about increased accessibility and appeal of the drug to youth. The objective of
      this study was to assess the impact of medical marijuana legalization across the
      United States by comparing trends in adolescent marijuana use between states with
      and without legalization of medical marijuana. METHODS: The study utilized data
      from the Youth Risk Behavioral Surveillance Survey between 1991 and 2011. States
      with a medical marijuana law for which at least two cycles of Youth Risk
      Behavioral Surveillance data were available before and after the implementation
      of the law were selected for analysis. Each of these states was paired with a
      state in geographic proximity that had not implemented the law. Chi-squared
      analysis was used to compare characteristics between states with and without
      medical marijuana use policies. A difference-in-difference regression was
      performed to control for time-invariant factors relating to drug use in each
      state, isolating the policy effect, and then calculated the marginal
      probabilities of policy change on the binary dependent variable. RESULTS: The
      estimation sample was 11,703,100 students. Across years and states, past-month
      marijuana use was common (20.9%, 95% confidence interval 20.3-21.4). There were
      no statistically significant differences in marijuana use before and after policy
      change for any state pairing. In the regression analysis, we did not find an
      overall increased probability of marijuana use related to the policy change
      (marginal probability .007, 95% confidence interval -.007, .02). CONCLUSIONS:
      This study did not find increases in adolescent marijuana use related to
      legalization of medical marijuana.

PMID- 24742759
TI  - Dopamine receptor gene d4 polymorphisms and early sexual onset: gender and
      environmental moderation in a sample of african-american youth.
AB  - PURPOSE: Early sexual onset and its consequences disproportionately affect
      African-American youth, particularly male youth. The dopamine receptor D4 gene
      (DRD4) has been linked to sexual activity and other forms of appetitive behavior,
      particularly for male youth and in combination with environmental factors (gene *
      environment [G * E] effects). The differential susceptibility perspective
      suggests that DRD4 may exert this effect by amplifying the effects of both
      positive and negative environments. We hypothesized that DRD4 status would
      amplify the influence of both positive and negative neighborhood environments on
      early sexual onset among male, but not female, African-Americans. METHODS:
      Hypotheses were tested with self-report, biospecimen, and census data from five
      prospective studies of male and female African-American youth in rural Georgia
      communities, N = 1,677. Early sexual onset was defined as intercourse before age
      14. RESULTS: No significant G * E findings emerged for female youth. Male youth
      with a DRD4 long allele were more likely than those with two DRD4 short alleles
      to report early sexual onset in negative community environments and not to report
      early onset in positive community environments. CONCLUSIONS: Dopaminergic
      regulation of adolescent sexual behaviors may operate differently by gender. DRD4
      operated as an environmental amplification rather than a vulnerability factor.

PMID- 24742760
TI  - Re: positive surgical margins in robot-assisted partial nephrectomy: a multi
      institutional analysis of oncologic outcomes (leave no tumor behind): A.
      Khalifeh, J. H. Kaouk, S. Bhayani, C. Rogers, m. Stifelman, Y. S. Tanagho, R.
      Kumar, M. A. Gorin, G. Sivarajan, D. Samarasekera and M. E. Allaf J Urol
      2013;190:1674-1679.

PMID- 24742761
TI  - Reply by authors.

PMID- 24742762
TI  - Re: are osteotomies necessary for bladder exstrophy closure?: J. G. Borer J Urol
      2014;191:13-14.

PMID- 24742763
TI  - Re: development of an instrument to assess the health related quality of life of
      kidney stone formers: K. L. Penniston and S. Y. Nakada J Urol 2013;189:921-930.

PMID- 24742764
TI  - Re: the electronic medical record: how not to communicate: W. D. Steers J Urol
      2013;190:1636-1637.

PMID- 24742765
TI  - The Carotid intima-media thickness modification following atorvastatin is bound
      to the modification of the oxidative balance.
AB  - BACKGROUND: Despite the reduction in cholesterol (CH) levels, the modification of
      carotid intima-media thickness (CIMT) is not evident in all the patients treated
      with statins. Activities other than CH reduction may determine the improvement in
      CIMT. METHODS: Twenty-two patients with hypercholesterolemia (aged 45-60; males)
      with CIMT increase started the treatment with atorvastatin. The CIMT (via
      echography), CH level, and the oxidative balance (OB) were measured at baseline
      and after 4 weeks. The OB consisted of the determination of the plasmatic
      hydroperoxides (reactive oxygen metabolites [d-ROMs] test) and the antioxidant
      reserve (plasma antioxidants test [PAT]). The d-ROMs/CH and PAT/CH ratios allowed
      to measure, respectively, the oxidative index (OI) and the protective index (PI).
      The OI/PI ratio represented the OB Risk Index (OBRI) to be compared with the CIMT
      modifications. RESULTS: An average reduction of 22% in CH was achieved in the
      group of patients together with an increase in both OI and PI (16% and 39%
      respectively) with a significant improvement in OBRI from 2.6 to 1.7 (analysis of
      variance P < .01). A reduction of >20% in CIMT was obtained in 10 patients
      whereas in the 12 patients no modification of CIMT was detected, despite the same
      CH reduction (-55 +/- 24.8 and -66 +/- 27.1 mg/dL respectively; P > .05). Only
      those patients with a decrease in OBRI >=0.8 showed a reduction in CIMT >20%.
      CONCLUSIONS: In this preliminary study, a significant modification in CIMT was
      obtained with atorvastatin treatment only in those patients showing an
      improvement in the OB (OBRI > 0.8).

PMID- 24742766
TI  - Gene therapy for restoring heart rhythm.
AB  - Efforts to use gene therapy to create a biological pacemaker as an adjunct or
      replacement of electronic pacemakers have been ongoing for about 15 years. For
      the past decade, most of these efforts have focused on the hyperpolarization
      activated cyclic nucleotide gated-(HCN) gene family of channels alone or in
      combination with other genes. The HCN gene family is the molecular correlate of
      the cardiac pacemaker current, If. It is a suitable basis for a biological
      pacemaker because it generates a depolarizing inward current primarily during
      diastole and is directly regulated by cyclic adenosine monophosphate (cAMP),
      thereby incorporating autonomic responsiveness. However, biological pacemakers
      based either on native HCN channels or on mutated HCN channels designed to
      optimize biophysical characteristics have failed to attain the desired basal and
      maximal physiological heart rates in large animals. More recent work has explored
      dual gene therapy approaches, combining an HCN variant with another gene to
      reduce outward current, increase an additional inward current, or enhance cAMP
      synthesis. Several of these dual gene therapy approaches have demonstrated
      appropriate basal and maximal heart rates with little or no reliance on a backup
      electronic pacemaker during the period of study. Future research, besides
      examining the efficacy of other gene combinations, will need to consider the
      additional issues of safety and persistence of the viral vectors often used to
      deliver these genes to a specific cardiac region. 

PMID- 24742767
TI  - Comparative antiatherogenic effects of intravenous AAV8- and AAV2-mediated ApoA
      IMilano gene transfer in hypercholesterolemic mice.
AB  - Apolipoprotein A-IMilano (ApoA-IM), a naturally occurring Arg173 to Cys mutant of
      ApoA-I, has been shown to reduce atherosclerosis in animal models and in a small
      phase 2 human trial. We have shown superior atheroprotective effects of ApoA-IM
      gene compared with wild-type ApoA-I gene using transplantation of retrovirally
      transduced bone marrow in ApoA-I/ApoE null mice. In this study, we compared the
      antiatherogenic efficacy of ApoA-IM gene transfer using Recombinant adeno
      associated virus (rAAV) 2 or rAAV8 as vectors in ApoA-I/ApoE null mice. Mice
      received a single intravenous injection of 1.2 * 10(12) vector genomes of AAV2 or
      AAV8 vectors expressing ApoA-IM or control empty vectors (12 mice/group).
      Circulating levels of ApoA-IM were higher in recipients of AAV8 compared with
      AAV2 at 4, 12, and 20 weeks postinjection. Qualitative polymerase chain reaction
      analysis of RNA collected from different tissues showed that the AAV8-mediated
      gene transfer resulted in a more efficient transgene expression in the heart,
      brain, liver, lung, spleen, and kidney of the recipient mice compared with AAV2.
      Intravenous AAV8-ApoA-IM injection reduced atherosclerosis in the whole aorta (P
      < .01), aortic sinuses (P < .05), and brachiocephalic arteries (P < .05) compared
      with the vector control, whereas there was no statistically significant reduction
      in atherosclerosis in mice receiving intravenous AAV2-ApoA-IM. The ApoA-IM gene
      was expressed in the aortic tissue of mice receiving AAV8 ApoA-IM but not in
      those receiving AAV2 ApoA-IM. Immunostaining showed that compared with the vector
      control, there was reduced macrophage content in the brachiocephalic (P < .05)
      and aortic sinus plaques (P < .05) of AAV8 ApoA-IM recipients but not in the
      recipients of AAV2 ApoA-IM. Thus, intravenous injection of AAV8 is more effective
      than intravenous injection of AAV2 in the expression of ApoA-IM gene. These data
      provide support for the potential feasibility of this approach for
      atheroprotection in humans.

PMID- 24742768
TI  - Conversion from sildenafil to tadalafil: results from the sildenafil to tadalafil
      in pulmonary arterial hypertension (SITAR) study.
AB  - PURPOSE: Among phosphodiesterase type 5 inhibitors, tadalafil offers clinicians a
      once-daily alternative to 3 times daily sildenafil for the treatment of pulmonary
      arterial hypertension (PAH). This study assessed the safety and patient
      satisfaction with conversion from sildenafil to tadalafil. METHODS: In this
      multicenter, prospective, 6-month study, patients with PAH were instructed to
      take their last dose of sildenafil in the evening and initiate tadalafil 40 mg/d
      the next morning. Patients completed the Treatment Satisfaction Questionnaire for
      Medication at baseline and 30, 90, and 180 days after transition to assess PAH
      symptoms and patient satisfaction. Safety was assessed on the basis of recorded
      adverse events (AEs). RESULTS: Of the 35 patients who met the study criteria, 56%
      were receiving >=2 PAH therapies. At the time of transition, the sildenafil dose
      ranged from 40 to 300 mg/d, with 20% of the patients on >20 mg of sildenafil 3
      times daily. Transition to tadalafil was generally well tolerated, and the
      incidence of common AEs, except for myalgia, appeared to decrease over time on
      tadalafil therapy. Five (14%) patients switched back to sildenafil. A greater
      percentage of patients were satisfied than were dissatisfied after conversion to
      tadalafil (55% vs 19% at 90 days), while 26% felt about the same degree of
      satisfaction. Conversion to tadalafil resulted in significant improvement in
      patient ratings of therapy convenience. CONCLUSIONS: Transition of patients from
      sildenafil to tadalafil was usually well tolerated, with improved convenience and
      may enhance treatment satisfaction.

PMID- 24742769
TI  - A novel amiodarone-eluting biological glue for reducing postoperative atrial
      fibrillation: first animal trial.
AB  - OBJECTIVE: Postoperative atrial fibrillation (POAF) is the most common
      complication after cardiac surgery, leading to increased morbidity and mortality.
      The aim of this preliminary study was to evaluate a novel drug delivery system
      for local release of amiodarone. METHODS: In the current prospective study, 9
      goats underwent attachment of right atrial (RA) epicardial electrodes. Alginate
      based glue with amiodarone was applied to the RA of the treatment groups. Rapid
      atrial response (RAR) to burst pacing was assessed before application and in the
      third postoperative day (POD3). Average RAR frequency was defined as the average
      percentage of inductions resulting in RAR per animal. Myocardial and extracardiac
      tissue amiodarone concentrations were analyzed. RESULTS: Differences in RAR
      proportions between baseline and POD3 were greater in the treatment group versus
      the control group (P = .034). Average RAR frequency was reduced by 34% in the
      treatment group (baseline: 65%; POD3: 31%), while it was increased by 11.3% in
      the control (baseline:43.8%; POD3: 55%). The treatment group demonstrated a
      greater proportion of animals meeting the success criterion of net percentage
      reduction in RAR frequency greater than 25% (P = .047). The average amount of
      total amiodarone detected in the RA was 104.4 +/- 28.9 ug; the transmural
      concentration was linearly distributed (P < .0001). Extracardiac tissue
      concentrations were below the detection level. CONCLUSIONS: Local alginate-based
      amiodarone delivery demonstrated an RAR frequency reduction of clinical
      importance in response to burst pacing. The electrophysiological response was
      achieved while maintaining below-detection systemic drug levels. Current findings
      may point to the system's future applicability in reducing POAF risk in humans.

PMID- 24742770
TI  - Arrhythmia: 100 years on from George Ralph Mines.

PMID- 24742771
TI  - UPLC-ESI-Q-TOF-MS(E) identification of urinary metabolites of the emerging sport
      nutrition supplement methoxyisoflavone in human subjects.
AB  - Methoxyisoflavone (5-methyl-7-methoxyisoflavone) is a synthetic isoflavone used
      by bodybuilders for its ergogenic properties. A recent study demonstrated that
      methoxyisoflavone metabolites can induce false-positive results in urinary
      immunoassay screening tests for cannabinoids, and only one metabolite has been
      identified. To improve the knowledge on the metabolic pathways of
      methoxyisoflavone, ultra-performance liquid chromatography quadrupole time-of
      flight mass spectrometry (UPLC-Q-TOF) was applied. Urine samples were obtained
      from methoxyisoflavone regular users. After enzymatic hydrolysis and liquid
      liquid extraction, the samples were analyzed by UPLC-Q-TOF fitted with an
      electrospray ionization source (ESI) operating under positive ion mode. Mass data
      were acquired with the MS(E) method. Five metabolites were identified. Those were
      divided into two metabolic pathways, depending on whether the B ring
      hydroxylation was preceded or not by the O-demethylation of the methoxy group.
      The MS(E) mass spectra of methoxyisoflavone and its metabolites are specific of
      isoflavones structures and revealed 1,3 retro Diels-Alder fragmentation and
      double CO loss. Losses of small neutral molecules CO and H2O, and radical CH3,
      typical of flavonoids, were also observed. This study illustrates the capacity of
      the sensitive UPLC-Q-TOF analytical system, combined with the MS(E) method of
      collection of fragmentation data, to rapidly elucidate the unknown xenobiotics
      metabolism. 

PMID- 24742772
TI  - Implementation of design of experiments for optimization of forced degradation
      conditions and development of a stability-indicating method for furosemide.
AB  - The study involved optimization of forced degradation conditions and development
      of a stability-indicating method (SIM) for furosemide employing the design of
      experiment (DoE) concept. The optimization of forced degradation conditions,
      especially hydrolytic and oxidative, was done by application of 2(n) full
      factorial designs, which helped to obtain the targeted 20-30% drug degradation
      and also enriched levels of degradation products (DPs). For the selective
      separation of the drug and its DPs for the development of SIM, DoE was applied in
      three different stages, i.e., primary parameter selection, secondary parameter
      screening and method optimization. For these three, IV-optimal, Taguchi
      orthogonal array and face-centred central composite designs were employed,
      respectively. The organic modifier, buffer pH, gradient time and initial hold
      time were selected as primary parameters. Initial and final organic modifier
      percentage, and flow rate came out as critical parameters during secondary
      parameter screening, which were further evaluated during method optimization.
      Based on DoE results, an optimized method was obtained wherein a total of twelve
      DPs were separated successfully. The study also exposed the degradation behaviour
      of the drug in different forced degradation conditions. 

PMID- 24742773
TI  - The effect of assay type and sample matrix on detected cytokine concentrations in
      human blood serum and nasal lavage fluid.
AB  - Cytokine concentrations in biological fluids are widely used markers for
      activation of immunological processes. Confirming the reproducibility of
      measurements is important, especially in longitudinal or multicenter studies
      where time between analyses or different analyzing laboratories increases the
      intra-assay variability. In this study, the reproducibility of the cytokine
      analysis conducted with different assay platforms was studied by comparing the
      results of two cytokines [interleukin (IL)-6 in serum and nasal lavage fluid
      (NAL) and IL-8 in NAL] analyzed with Meso Scale Discovery (MSD) ultra-sensitive
      single and multiplex assay kits (n=76). In addition, the difference in cytokine
      levels between two biological sample matrices was studied by comparing the
      results of altogether 9 cytokines [IL-6, IL-2, IL-8, IL12p70, IL-1beta,
      granulocyte-macrophage colony-stimulating factor (GM-CSF), interferon (IFN)gamma,
      IL-10 and tumor necrosis factor (TNF)alpha] measured from serum and NAL of the
      same study subjects (n=460). The results show that the cytokine concentrations
      analyzed with single and multiplex assays are concordant but not equal.
      Comparison of the different matrices revealed that cytokine concentrations in
      serum do not correspond with concentrations detected in nasal lavage fluid. It
      can be concluded that comparability of the results from single and multiplex
      analysis of cytokines is high, but the concentrations should not be compared
      directly with each other. The differences between concentrations analyzed from
      serum and nasal lavage fluid indicate that the levels are specific for each
      matrix and represent distinct immunological conditions. 

PMID- 24742774
TI  - Risk factors and bacterial spectrum for pneumonia after abdominal surgery in
      elderly Chinese patients.
AB  - Postoperative pneumonia is a common complication of abdominal surgery in the
      elderly. The aim of this study was to determine risk factors and bacterial
      spectrum for pneumonia after abdominal surgery in elderly Chinese patients. We
      performed a case-control study in a total of 5431 patients aged 65 years and over
      who had undergone abdominal surgery at the 2nd affiliated hospital of Kunming
      medical college between June 2003 and June 2011. Postoperative pneumonia
      developed in 86 patients (1.58%). Gram-negative bacilli were the principal
      microorganisms (82.86%) isolated from patients. The most common organisms
      isolated were Klebsiella spp. (28.57%), Acinetobacter spp. (17.14%) and
      Pseudomonas aeruginosa (17.14%). Multivariate analysis confirmed the following to
      be independent risk factors for postoperative pneumonia in the elderly after
      abdominal surgery: age >=70 (OR 1.93, 95% CI 1.16-3.22, p=0.01), upper abdominal
      surgery (OR 2.07, 95% CI 1.18-3.64, p=0.01) and duration of operation >3 h (OR
      2.48, 95% CI 1.49-4.15, p=0.00). Identifying these risk factors may help achieve
      better prevention and treatment for postoperative pneumonia in elderly patients
      after abdominal surgery.

PMID- 24742775
TI  - Does vitamin D deficiency increase orthostatic hypotension risk in the elderly
      patients?
AB  - Orthostatic hypotension (OH) is closely associated with falls, cardiovascular
      events and mortality in the elderly patients. The aim of the study is to evaluate
      the OH prevalence among patients over the age of 65 years, to find out the impact
      of this condition on daily living activities, and to determine the possible
      effects of vitamin D levels on OH in elderly patients. Eight hundred and forty
      nine geriatric patients who had undergone comprehensive geriatric assessment were
      retrospectively evaluated and 546 patients were included in the study. The
      patient's demographic characteristics, blood pressures, comorbid diseases,
      polypharmacy status, cognitive and nutritional states, basic and instrumental
      daily living activity indexes and laboratory values were obtained from hospital
      files. Serum 25-hydroxyvitamin D [25(OH)D] was measured by radioimmunoassay. The
      prevalence of OH was found to be 27.5%. Both daily living activity indexes were
      significantly lower in older patients with OH (p<0.02), and serum 25(OH)D levels
      were significantly lower in older patients with OH (p<0.01). Our findings suggest
      that vitamin D deficiency may be a factor in OH development. Because this
      condition is also preventable and correctable, serum vitamin D levels should be
      checked during the evaluation of OH patients and any detected deficiency should
      be treated accordingly. 

PMID- 24742776
TI  - Falls and self-assessment of eyesight among elderly people: a population-based
      study in a south Brazilian municipality.
AB  - This paper seeks to verify the association between falls and self-assessment of
      visual acuity in elderly people by means of a cross-sectional population-based
      study involving 1593 elderly people (aged 60 or over) from the urban zone of the
      municipality of Bage-RS. Poisson regression was used for association analysis.
      Fall prevalence in the last year was 28.0% (95%CI: 25.8; 30.2), with 45.0% of
      these having suffered two or more falls in the same period. Elderly people self
      assessing their eyesight as bad/very poor (10.0%) or regular (33.3%) showed a
      linear increase in fall occurrence when compared to individuals who considered
      their eyesight to be good/excellent. Self-assessment of eyesight showed itself to
      be an important factor associated with the occurrence of falls. This results
      entails the need to make progress with tracing elderly people with eyesight
      difficulties and its possible impact on actions to prevent the occurrence of
      falls. 

PMID- 24742777
TI  - The frequency of diagnostic errors in outpatient care: estimations from three
      large observational studies involving US adult populations.
AB  - BACKGROUND: The frequency of outpatient diagnostic errors is challenging to
      determine due to varying error definitions and the need to review data across
      multiple providers and care settings over time. We estimated the frequency of
      diagnostic errors in the US adult population by synthesising data from three
      previous studies of clinic-based populations that used conceptually similar
      definitions of diagnostic error. METHODS: Data sources included two previous
      studies that used electronic triggers, or algorithms, to detect unusual patterns
      of return visits after an initial primary care visit or lack of follow-up of
      abnormal clinical findings related to colorectal cancer, both suggestive of
      diagnostic errors. A third study examined consecutive cases of lung cancer. In
      all three studies, diagnostic errors were confirmed through chart review and
      defined as missed opportunities to make a timely or correct diagnosis based on
      available evidence. We extrapolated the frequency of diagnostic error obtained
      from our studies to the US adult population, using the primary care study to
      estimate rates of diagnostic error for acute conditions (and exacerbations of
      existing conditions) and the two cancer studies to conservatively estimate rates
      of missed diagnosis of colorectal and lung cancer (as proxies for other serious
      chronic conditions). RESULTS: Combining estimates from the three studies yielded
      a rate of outpatient diagnostic errors of 5.08%, or approximately 12 million US
      adults every year. Based upon previous work, we estimate that about half of these
      errors could potentially be harmful. CONCLUSIONS: Our population-based estimate
      suggests that diagnostic errors affect at least 1 in 20 US adults. This
      foundational evidence should encourage policymakers, healthcare organisations and
      researchers to start measuring and reducing diagnostic errors.

PMID- 24742778
TI  - The effect of the electronic transmission of prescriptions on dispensing errors
      and prescription enhancements made in English community pharmacies: a
      naturalistic stepped wedge study.
AB  - OBJECTIVES: To compare prevalence and types of dispensing errors and pharmacists'
      labelling enhancements, for prescriptions transmitted electronically versus paper
      prescriptions. DESIGN: Naturalistic stepped wedge study. SETTING: 15 English
      community pharmacies. INTERVENTION: Electronic transmission of prescriptions
      between prescriber and pharmacy. MAIN OUTCOME MEASURES: Prevalence of labelling
      errors, content errors and labelling enhancements (beneficial additions to the
      instructions), as identified by researchers visiting each pharmacy. RESULTS:
      Overall, we identified labelling errors in 5.4% of 16,357 dispensed items, and
      content errors in 1.4%; enhancements were made for 13.6%. Pharmacists also edited
      the label for a further 21.9% of electronically transmitted items. Electronically
      transmitted prescriptions had a higher prevalence of labelling errors (7.4% of
      3733 items) than other prescriptions (4.8% of 12,624); OR 1.46 (95% CI 1.21 to
      1.76). There was no difference for content errors or enhancements. The increase
      in labelling errors was mainly accounted for by errors (mainly at one pharmacy)
      involving omission of the indication, where specified by the prescriber, from the
      label. A sensitivity analysis in which these cases (n=158) were not considered
      errors revealed no remaining difference between prescription types. CONCLUSIONS:
      We identified a higher prevalence of labelling errors for items transmitted
      electronically, but this was predominantly accounted for by local practice in a
      single pharmacy, independent of prescription type. Community pharmacists made
      labelling enhancements to about one in seven dispensed items, whether
      electronically transmitted or not. Community pharmacists, prescribers,
      professional bodies and software providers should work together to agree how
      items should be dispensed and labelled to best reap the benefits of
      electronically transmitted prescriptions. Community pharmacists need to ensure
      their computer systems are promptly updated to help reduce errors.

PMID- 24742779
TI  - Adverse drug events and medication errors in Japanese paediatric inpatients: a
      retrospective cohort study.
AB  - OBJECTIVES: Knowledge about the epidemiology of adverse drug events (ADEs) and
      medication errors in paediatric inpatients is limited outside Western countries.
      To improve paediatric patient safety worldwide, assessing local epidemiology is
      essential. DESIGN: The Japan Adverse Drug Events (JADE) Study was a cohort study.
      SETTING: Paediatric inpatients at two tertiary care teaching hospitals in Japan.
      MAIN OUTCOME MEASURES: ADEs and medication errors identified by onsite review of
      all medical charts, incident reports and prescription queries by pharmacists. Two
      independent physicians reviewed all incidents and classified ADEs and medication
      errors, as well as their severity and preventability. RESULTS: We enrolled 1189
      admissions which included 12,691 patient-days during the study period, and
      identified 480 ADEs and 826 medication errors. The incidence of ADEs was 37.8
      (95% CI 34.4 to 41.2) per 1000 patient-days and that of medication errors was
      65.1 (95% CI 60.6 to 69.5) per 1000 patient-days. Among ADEs, 4%, 23% and 73%
      were fatal or life-threatening, serious and significant, respectively. Among the
      480 ADEs, 36 (8%) were considered to be preventable which accounted for 4% of all
      medication errors, while 668 (81%) of all medication errors were judged to have
      the potential to cause harm to patients. The most common error stage for
      preventable ADEs was monitoring (78%) whereas 95% of potential ADEs occurred at
      the ordering stage. CONCLUSIONS: ADEs and medication errors were common in
      paediatric inpatients in Japan, though the proportion of ADEs that were
      preventable was low. The ordering and monitoring stages appeared most important
      for improving safety.

PMID- 24742781
TI  - Inpatient costs of fire-related injuries in Finland.
AB  - The aim of this study was to approximate the direct health care costs of fire
      related injuries in inpatient care in Finland. Using the PERFECT costing method,
      cost data from both Finnish burn centres were linked to the fire-related injury
      patient data from the Finnish National Hospital Discharge Register (FHDR, 2001
      2009). Additionally, a sample of 168 patients from the Helsinki Burn Centre was
      linked to the FHDR to examine the relation of %TBSA. Burn was involved in
      approximately 77% of the cases, the remainder consisting mainly of combustion gas
      poisonings. Burns were generally much more expensive to treat. Fire-related
      injuries incurred EUR 6.2 million per year in inpatient costs for the whole
      country. Mean cost per burn patient was EUR 25,000 and for combustion gas
      poisoning it was EUR 3600. As expected there was a strong relationship between
      %TBSA and cost. Older age had a strong effect on costs. The most severe injuries
      cost over EUR 400,000 to treat. Approximately 7-8% of the most expensive cases
      constitute 50% of the total costs. Successful prevention of extreme cases would
      yield considerable savings in relation to total annual inpatient care costs.
      However, a cost-benefit analysis would be needed. 

PMID- 24742780
TI  - Burnout in the NICU setting and its relation to safety culture.
AB  - BACKGROUND: Burnout is widespread among healthcare providers and is associated
      with adverse safety behaviours, operational and clinical outcomes. Little is
      known with regard to the explanatory links between burnout and these adverse
      outcomes. OBJECTIVES: (1) Test the psychometric properties of a brief four-item
      burnout scale, (2) Provide neonatal intensive care unit (NICU) burnout and
      resilience benchmarking data across different units and caregiver types, (3)
      Examine the relationships between caregiver burnout and patient safety culture.
      RESEARCH DESIGN: Cross-sectional survey study. SUBJECTS: Nurses, nurse
      practitioners, respiratory care providers and physicians in 44 NICUs. MEASURES:
      Caregiver assessments of burnout and safety culture. RESULTS: Of 3294
      administered surveys, 2073 were returned for an overall response rate of 62.9%.
      The percentage of respondents in each NICU reporting burnout ranged from 7.5% to
      54.4% (mean=25.9%, SD=10.8). The four-item burnout scale was reliable
      (alpha=0.85) and appropriate for aggregation (intra-class correlation coefficient
      2=0.95). Burnout varied significantly between NICUs, p<0.0001, but was less
      prevalent in physicians (mean=15.1%, SD=19.6) compared with non-physicians
      (mean=26.9%, SD=11.4, p=0.0004). NICUs with more burnout had lower teamwork
      climate (r=-0.48, p=0.001), safety climate (r=-0.40, p=0.01), job satisfaction
      (r=-0.64, p<0.0001), perceptions of management (r=-0.50, p=0.0006) and working
      conditions (r=-0.45, p=0.002). CONCLUSIONS: NICU caregiver burnout appears to
      have 'climate-like' features, is prevalent, and associated with lower perceptions
      of patient safety culture.

PMID- 24742782
TI  - Looking in the mirror for the first time after facial burns: a retrospective
      mixed methods study.
AB  - Appearance-related concerns are common following burns. However, there is minimal
      research that has specifically investigated patients' reactions when they looked
      in the mirror for the first time following facial burns. The current study aimed
      to investigate patients' reactions and factors associated with distress. Burns
      patients (n=35) who had sustained facial injuries completed a questionnaire which
      examined their reactions when looking in the mirror for the first time. Data were
      collected between April and July 2013. Participants had sustained their burns 12
      months prior to participating, on average (ranging from one to 24 months). Forty
      seven percent (n=16) of patients were worried about looking for the first time,
      55% (n=19) were concerned about what they would see, and 42% (n=14) held negative
      mental images about what their faces looked like before they looked. Twenty-seven
      percent (n=9) of patients initially avoided looking, 38% (n=13) tried to 'read'
      others' reactions to them to try to gauge what they looked like, and 73% (n=25)
      believed that it was important for them to look. Mean ratings suggested that
      patients found the experience moderately distressing. Patients most often found
      the experience less distressing compared to their expectations. Distress was
      related to feeling less prepared, more worried and increased negative mental
      images prior to looking. In conclusion, patients' reactions to looking in the
      mirror for the first time vary. Adequately preparing patients and investigating
      their expectations beforehand is crucial. The findings have a number of important
      implications for practice. 

PMID- 24742783
TI  - Cross-species analysis of genetically engineered mouse models of MAPK-driven
      colorectal cancer identifies hallmarks of the human disease.
AB  - Effective treatment options for advanced colorectal cancer (CRC) are limited,
      survival rates are poor and this disease continues to be a leading cause of
      cancer-related deaths worldwide. Despite being a highly heterogeneous disease, a
      large subset of individuals with sporadic CRC typically harbor relatively few
      established 'driver' lesions. Here, we describe a collection of genetically
      engineered mouse models (GEMMs) of sporadic CRC that combine lesions frequently
      altered in human patients, including well-characterized tumor suppressors and
      activators of MAPK signaling. Primary tumors from these models were profiled, and
      individual GEMM tumors segregated into groups based on their genotypes. Unique
      allelic and genotypic expression signatures were generated from these GEMMs and
      applied to clinically annotated human CRC patient samples. We provide evidence
      that a Kras signature derived from these GEMMs is capable of distinguishing human
      tumors harboring KRAS mutation, and tracks with poor prognosis in two independent
      human patient cohorts. Furthermore, the analysis of a panel of human CRC cell
      lines suggests that high expression of the GEMM Kras signature correlates with
      sensitivity to targeted pathway inhibitors. Together, these findings implicate
      GEMMs as powerful preclinical tools with the capacity to recapitulate relevant
      human disease biology, and support the use of genetic signatures generated in
      these models to facilitate future drug discovery and validation efforts.

PMID- 24742785
TI  - Integration of lignin and acrylic monomers towards grafted copolymers by free
      radical polymerization.
AB  - Three kinds of acrylic monomers (2,2,3,4,4,4-hexafluorobutyl methacrylate
      (HFBMA), methyl methacrylate (MMA) and butyl acrylate (BA)) were utilized to
      modify the lignin (BBL) by "grafting from" free radical polymerization (FRP),
      respectively. Calcium chloride/hydrogen peroxide (CaCl2/H2O2) was used as
      initiator. Effects of monomer type and concentration, initiator concentration and
      polymerization time on grafting from BBL were studied. Grafting of poly (acrylic
      monomers) onto BBL was verified by the following characterizations and this
      synthesis method was found to be high efficient and selective for grafting
      polymerization of BBL. The presence of the BBL moiety in the backbone also
      resulted in higher glass transition temperature compared with the homopolymer of
      each monomer, and some modified copolymers also improved its thermal stability.
      All modifications made BBL more hydrophobic and the static contact angles of
      these modified copolymers were above 80 degrees . XPS analysis revealed that the
      surface of these modified BBL copolymers were dominated by acrylate monomer
      moiety. Additionally, the BBL-g-PBA copolymers can be used as dispersion
      modifiers in PLA-based materials to enhance UV absorption. 

PMID- 24742784
TI  - Balance between the two kinin receptors in the progression of experimental focal
      and segmental glomerulosclerosis in mice.
AB  - Focal and segmental glomerulosclerosis (FSGS) is one of the most important renal
      diseases related to end-stage renal failure. Bradykinin has been implicated in
      the pathogenesis of renal inflammation, whereas the role of its receptor 2
      (B2RBK; also known as BDKRB2) in FSGS has not been studied. FSGS was induced in
      wild-type and B2RBK-knockout mice by a single intravenous injection of Adriamycin
      (ADM). In order to further modulate the kinin receptors, the animals were also
      treated with the B2RBK antagonist HOE-140 and the B1RBK antagonist DALBK. Here,
      we show that the blockage of B2RBK with HOE-140 protects mice from the
      development of FSGS, including podocyte foot process effacement and the re
      establishment of slit-diaphragm-related proteins. However, B2RBK-knockout mice
      were not protected from FSGS. These opposite results were due to B1RBK
      expression. B1RBK was upregulated after the injection of ADM and this
      upregulation was exacerbated in B2RBK-knockout animals. Furthermore, treatment
      with HOE-140 downregulated the B1RBK receptor. The blockage of B1RBK in B2RBK
      knockout animals promoted FSGS regression, with a less-inflammatory phenotype.
      These results indicate a deleterious role of both kinin receptors in an FSGS
      model and suggest a possible cross-talk between them in the progression of
      disease.

PMID- 24742786
TI  - A psychometric evaluation of the functional assessment of chronic illness therapy
      palliative care (FACIT-Pal) scale with palliative care samples in three African
      countries.
AB  - CONTEXT: Although sub-Saharan Africa suffers the greatest burden of progressive
      illness, there are few outcome measures with adequate properties to measure needs
      and outcomes. OBJECTIVES: To examine the psychometric properties of the
      Functional Assessment of Chronic Illness Therapy-Palliative Care (FACIT-Pal)
      among people receiving palliative care in three African countries. METHODS: Adult
      patients in South Africa, Kenya, and Uganda gave self-reported data to the core
      FACIT-G plus Pal subscale. Data were subjected to factor analysis, corrected item
      total correlations, and Cronbach's alpha for full scale and subscales. RESULTS:
      The resulting four factors bear a strong similarity to the original Functional
      Assessment of Cancer Therapy-General in our sample of 461: physical symptoms,
      functional well-being, friends and family, and emotional well-being. Cronbach's
      alpha for the full 27-item scale was 0.90 and for the physical well-being,
      social/family well-being, emotional well-being, and functional well-being
      subscales, it was 0.83, 0.78, 0.80, and 0.87, respectively. Varimax rotation of
      the 19-item FACIT-Pal scale showed three clear interpretable factors. Factor 1, a
      sense of purpose and meaning in life; Factor 2, physical symptoms; and Factor 3,
      social integration. For the 19-item FACIT-Pal, Cronbach's alpha was 0.81, and
      individual corrected item-total correlations ranged from 0.24 to 0.61. Cronbach's
      alpha for the eight items comprising Factor 1 (meaning in life) was 0.83. For the
      other two factors, it was 0.70 (physical symptoms, six items) and 0.68 (social
      integration, three items). CONCLUSION: The FACIT-Pal is a reliable
      multidimensional scale for people with life-limiting incurable diseases in sub
      Saharan Africa, and the observed factors are interpretable and clinically
      meaningful.

PMID- 24742787
TI  - Perceived discrimination in health care is associated with a greater burden of
      pain in sickle cell disease.
AB  - CONTEXT: Perceived discriminatory experiences in society have been associated
      with a higher burden of pain among some minority patient populations. OBJECTIVES:
      To describe the extent to which patients with sickle cell disease (SCD) perceive
      discrimination from health care providers and to examine the association of these
      experiences with the burden of chronic SCD pain. METHODS: Cross-sectional
      analysis of data collected at baseline of a prospective cohort study of SCD
      patient experiences of care (n = 291). Perceived race-based and disease-based
      discrimination from health care providers were measured using subscales adapted
      from the Interpersonal Processes of Care Survey. Discrimination scores were
      examined for their association with patient characteristics and measures of pain
      burden using descriptive, bivariate, and multivariate analytic techniques.
      RESULTS: Respondents reported a greater burden of race-based discrimination from
      health care providers than has been previously reported by African Americans, and
      they reported a greater amount of disease-based vs. race-based discrimination.
      Age and having difficulty persuading providers about pain were the only patient
      characteristics independently associated with race-based discrimination, whereas
      older age, greater emergency room utilization, having difficulty persuading
      providers about pain, daily chronic pain, fewer good days during a week, and a
      higher severity of pain on their good days were independently associated with
      greater disease-based discrimination. CONCLUSION: Perceived disease-based, but
      not race-based, discrimination was found to be associated with a greater range of
      self-reported pain among patients with SCD. If causal, this finding could signal
      an important new approach to mitigating the burden of pain experienced by persons
      with SCD.

PMID- 24742788
TI  - Trajectories of the multidimensional dying experience for terminally ill cancer
      patients.
AB  - CONTEXT: Studies exploring the trajectories of physical-psychological-social
      spiritual dying experiences frequently treat changes in these experiences as
      consistent across different domains and over time. OBJECTIVE: This prospective,
      longitudinal investigation was designed to characterize trajectories of the
      multidimensional dying experience for cancer patients in their last year of life.
      METHODS: Trajectories of physical-psychological-social-spiritual/existential
      dimensions and overall quality of life (QOL) were identified among 313 cancer
      patients using mixed-effects models to test for linear, quadratic, or cubic
      changes. Changes in each variable were evaluated for clinical significance using
      minimal important difference. RESULTS: When patients transitioned to their end of
      life, symptom distress, functional dependence, anxiety, and depressive symptoms
      slightly increased, followed by a stable status for approximately four to six
      months, and accelerated dramatically to the first clinically significant changes
      at three to four months before death. Perceived social support and post-traumatic
      growth declined gradually to clinically significant changes at one and four
      months before death, respectively. Perceived sense of burden to others increased
      steadily in the last year of life, with no clinically significant changes
      identified. Overall QOL deteriorated gradually in the last year but did not reach
      a clinically significant change until 2.5 months before death. CONCLUSION: All
      dimensions deteriorated in the last year of life but with distinctive physical
      psychological-social-spiritual/existential and overall QOL trajectories.
      Recognizing trajectory patterns and tipping points of accelerating deterioration
      in each dimension can help clinicians anticipate times of increased distress,
      initiate timely, effective interventions to relieve patient suffering, and
      facilitate high-quality end-of-life care tailored to patients' needs and
      preferences.

PMID- 24742789
TI  - [Perioperative management for liver transplant in a patient with familial amyloid
      polyneuropathy with heart involvement].
AB  - Familial amyloid polyneuropathy (FAP) is a systemic amyloidosis caused by mutated
      transthyretin. Cardiac amyloidosis, the major prognostic determinant in systemic
      amyloidosis, is characterized by infiltration of the myocardium, leading to
      cardiomyopathy and conduction disturbances. Liver transplantation is the only
      curative option for patients with FAP. The case is presented of a 36-year-old
      patient with type i FAP with cardiac involvement, proposed for liver transplant
      surgery, which was successfully performed without any preoperative event of
      interest. 

PMID- 24742790
TI  - [Neuraxial anesthesia for appendectomy in a patient with hereditary angioedema].

PMID- 24742791
TI  - [Prevalence of pain in Andalusian public hospitals].
AB  - OBJECTIVE: To determine the prevalence of pain in medical and surgical patients
      admitted to reference hospitals in Andalusia, as well as their features and the
      most population groups most affected. MATERIAL AND METHODS: A cross-sectional,
      multicenter epidemiological study was conducted simultaneously on the population
      admitted to 5 hospitals. Using a structured questionnaire the demographics,
      hospital area, presence of pain at the time of the interview, and pre- and post
      variables related to the intensity of pain and its treatment at 24h were
      investigated. All patients over 18 years old were included, except those patients
      with difficulty in understanding the questionnaire, and psychiatric and obstetric
      patients. Pain intensity was assessed by simple verbal scale. RESULTS: Of the
      1,236 patients included, 54.2% were male, with 51.1% of patients aged 65 years,
      and 69.17% were admitted to medical areas. Pain was observed in 52.9% of patients
      admitted to the surgical area compared to 29.4% in the medical area. Of the 19.4%
      who reported having had pain in the last 24h prior to the questionnaire, 57.7% of
      them were surgical patients and 32% were medical, P<.005), and of the 42.2% who
      had pain at the time of study, 52.7% were female. The incidence of pain on
      movement was higher than that observed at rest. The mean resting pain was 1.8 and
      1.4 for the surgical and medical patients, respectively (P<.01). The mean pain on
      movement was 2.2 and 1.6 for the surgical and medical patients, respectively
      (P<.01). More than one quarter (25.8%) of surgical patients and 16.5% of medical
      patients had difficulty sleeping (P<.005). Some 12.8% of all patients had no
      analgesic regimen, and 66.2% and 85.6% of surgical and medical patients,
      respectively, did not request analgesics (P<.005). The main drugs were prescribed
      paracetamol analgesic and metamizole, and in 54.4% of patients. CONCLUSIONS: We
      believe that the presence of pain in patients admitted to our study population is
      high and it is essential to encourage an improvement in the pain management of
      both acute and chronic pain processes.

PMID- 24742793
TI  - Using information from the violence risk scale to understand different patterns
      of change: an exploratory investigation of intensively treated life-sentenced
      prisoners.
AB  - Research rarely has shown that in-program change in correctional rehabilitation
      is related to long-term outcome (i.e., recidivism), and surprisingly little is
      known about what happens to progress after treatment, especially for "lifers"
      whose release may not be imminent. This study investigated patterns of treatment
      response for 35 life-sentenced treatment completers of an intensive cognitive
      behavioral program for high-risk male violent prisoners. Using Violence Risk
      Scale (VRS) ratings at pre-treatment, post-treatment, and 6 to 12 months
      following the program, we found that prisoners' mean treatment response was
      positive both at program end and follow-up. However, a fine-grained analysis
      identified five distinct change patterns within the sample. Importantly, the
      direction and volume of in-program change did not necessarily predict post
      program change, and the highest risk prisoners did not benefit as much as those
      at medium-high risk. The findings suggest that (a) a better understanding of the
      effects of treatment may be gained by examining change beyond the end of
      interventions, including a focus on the individual and contextual factors that
      promote and inhibit generalization and (b) more therapeutic attention may be
      warranted for monitoring treatment change to maximize conditions for continued
      gain beyond the end of the program. 

PMID- 24742794
TI  - Markers and measures of timeliness of cancer diagnosis after symptom onset: a
      conceptual framework and its implications.

PMID- 24742795
TI  - Cardiac disease in pregnancy.

PMID- 24742796
TI  - Bullous pemphigoid induced by cryotherapy.

PMID- 24742797
TI  - The stability of spike counts in children with interictal epileptiform activity.
AB  - PURPOSE: Little is known about the stability of serial measures of spike counts
      in children or whether spike counts are an inherently stable or unstable measure.
      We investigated the variation in first- and second-night spike counts in children
      undergoing 48-h ambulatory EEG recording. METHODS: We analyzed 40 consecutive 48
      h ambulatory EEGs performed at Boston Children's Hospital that manifested spikes
      but no seizures. Distinct spike foci in the same child were counted separately.
      We visually counted all spikes in the first 20min after the first sleep spindle
      during nighttime sleep, comparing the first and second nights. RESULTS: Fifty
      five unique spike foci were counted in 40 children (age range: 9 months to 19
      years; median: 8.4 years). Considerable variation was seen when comparing Night 1
      and Night 2 spike counts: for all foci, Night 1 mean and median spike counts were
      304.5 and 126 and Night 2 counts were 309.5 and 148, respectively. For each
      focus, the mean change in spike frequency between Night 1 and Night 2 was 42.1%
      (median=28.3%, IQR 19.0-50.0%). The coefficient of variation of 0.94 suggested a
      large amount of variation. The percentage change weighted according to high or
      low spike frequency was 25.1%. CONCLUSION: In 40 children with 55 unique spike
      foci, significant variability in spike frequency was seen between consecutive
      nights of sleep, suggesting significant natural variation in spike frequency. A
      quarter of spike foci varied by 50% or more. Spike counts separated by longer
      intervals may show even more dramatic natural variation.

PMID- 24742798
TI  - Clinical exome sequencing identifies a novel TUBB4A mutation in a child with
      static hypomyelinating leukodystrophy.
AB  - BACKGROUND: Leukodystrophies are a large group of inherited diseases of central
      nervous system myelin. There are few treatments, and most patients do not receive
      a final genetic diagnosis. PATIENT: We report a novel presentation of a female
      child with hypotonia, global developmental delay, and rotatory nystagmus. Brain
      MRI demonstrated profound hypomyelination and minimal or no atrophy in the brain
      stem or cerebellum. RESULTS: Extensive testing failed to yield a diagnosis until
      clinical whole-exome sequencing revealed a novel pathogenic mutation in the beta
      tubulin gene TUBB4A. TUBB4A is a cause of hereditary dystonia type 4 and has
      recently been reported to cause hypomyelination with atrophy of the basal ganglia
      and cerebellum. CONCLUSIONS: This report expands the phenotypic spectrum of
      TUBB4A-associated neurological diseases to include static hypomyelinating
      leukodystrophy and supports the clinical relevance of next-generation sequencing
      diagnosis approaches.

PMID- 24742799
TI  - Review of dextromethorphan administration in 18 patients with subacute
      methotrexate central nervous system toxicity.
AB  - BACKGROUND: The pathogenesis of methotrexate central nervous system toxicity is
      multifactorial, but it is likely related to central nervous system folate
      homeostasis. The use of folinate rescue has been described to decrease toxicity
      in patients who had received intrathecal methotrexate. It has also been described
      in previous studies that there is an elevated level of homocysteine in plasma and
      cerebrospinal fluid of patients who had received intrathecal methotrexate.
      Homocysteine is an N-methyl-D-aspartate receptor agonist. The use of
      dextromethorphan, noncompetitive N-methyl-D-aspartate receptor receptor
      antagonist, has been used in the treatment of sudden onset of neurological
      dysfunction associated with methotrexate toxicity. It remains unclear whether the
      dextromethorphan impacted the speed of recovery, and its use remains
      controversial. This study reviews the use of dextromethorphan in the setting of
      subacute methotrexate central nervous system toxicity. METHODS: Charts of 18
      patients who had sudden onset of neurological impairments after receiving
      methotrexate and were treated with dextromethorphan were reviewed. RESULT: The
      use of dextromethorphan in most of our patients resulted in symptomatic
      improvement. In this patient population, earlier administration of
      dextromethorphan resulted in faster improvement of impairments and led to
      prevention of recurrence of seizure activity induced by methotrexate central
      nervous system toxicity. CONCLUSIONS: Our study provides support for the use of
      dextromethorphan in patients with subacute methotrexate central nervous system
      toxicity.

PMID- 24742800
TI  - Sarcolemmal alpha and gamma sarcoglycan protein deficiencies in Turkish siblings
      with a novel missense mutation in the alpha sarcoglycan gene.
AB  - BACKGROUND: The sarcoglycan alpha gene, also known as the adhalin gene, is
      located on chromosome 17q21; mutations in this gene are associated with limb
      girdle muscular dystrophy type 2D. We describe two Turkish siblings with findings
      consistent with limb-girdle muscular dystrophy type 2D. The evaluation excluded a
      dystrophinopathy, which is the most common form of muscular dystrophy. PATIENTS:
      Both siblings had very high levels of creatinine phosphokinase and negative
      molecular tests for deletions and duplications of the dystrophin gene. The older
      boy presented at 8 years of age with an inability to climb steps and an abnormal
      gait. His younger brother was 5 years old and had similar symptoms. The muscle
      biopsy evaluation was performed only in the older brother. RESULTS: The muscle
      biopsy showed dystrophic features as well as a deficiency in the expression of
      two different glycoproteins: the alpha sarcoglycan and the gamma sarcoglycan.
      Sarcolemmal expressions of dystrophin and other sarcoglycans (beta and delta)
      were diffusely present. DNA analysis demonstrated the presence of previously
      unknown homozygous mutations [c.226 C > T (p.L76 F)] in exon 3 in the sarcoglycan
      alpha genes of both siblings. Similar heterozygous point mutations at the same
      locus were found in both parents, but the genes of beta, delta, and gamma
      sarcoglycan were normal in the remaining family members. CONCLUSIONS: We describe
      two siblings with limb-girdle muscular dystrophy type 2D with a novel missense
      mutation. These patients illustrate that the differential diagnosis of muscular
      dystrophies is impossible with clinical findings alone. Therefore, a muscle
      biopsy and DNA analysis remain essential methods for diagnosis of muscle
      diseases.

PMID- 24742801
TI  - Diffusion-weighted MRI "claw sign" improves differentiation of infectious from
      degenerative modic type 1 signal changes of the spine.
AB  - BACKGROUND AND PURPOSE: Modic type 1 degenerative signal changes can
      mimic/suggest infection, leading to additional costly and sometimes invasive
      investigations. This retrospective study analyzes the utility and accuracy of a
      novel, diffusion-weighted "claw sign" for distinguishing symptomatic type 1
      degeneration from vertebral diskitis/osteomyelitis. MATERIALS AND METHODS:
      Seventy-three patients with imaging features resembling type 1 degeneration were
      classified clinically into 3 groups: true degenerative type 1 changes (n = 33),
      confirmed diskitis/osteomyelitis (n = 20), and radiologically suspected infection
      later disproved clinically (n = 20). A claw sign was defined on DWI as well
      marginated, linear, regions of high signal situated within the adjacent vertebral
      bodies at the interface of normal with abnormal marrow. Two blinded
      neuroradiologists independently rated the presence of the claw sign, along with
      T2 disk signal and disk and endplate enhancement to determine the utility of each
      for identifying degeneration versus infection. RESULTS: When the 2
      neuroradiologists identified a definite claw, 38 of 39 patients (97%) and 29 of
      29 patients (100%) proved to be infection-free. When the readers identified a
      probable claw, 14 of 14 patients (100%) and 16 of 19 patients (84%) proved to be
      infection-free. Conversely, when the readers identified the absence of claw sign
      (diffuse DWI pattern), there was proved infection in 17 of 17 cases (100%) and 13
      of 14 cases (93%). CONCLUSIONS: In patients with type 1 signal changes of the
      vertebral disk space, a claw sign is highly suggestive of degeneration and its
      absence strongly suggests diskitis/osteomyelitis.

PMID- 24742802
TI  - Time-shift homotopic connectivity in mesial temporal lobe epilepsy.
AB  - BACKGROUND AND PURPOSE: Voxel-mirrored intrinsic functional connectivity allows
      the depiction of interhemispheric homotopic connections in the human brain,
      whereas time-shift intrinsic functional connectivity allows the detection of the
      extent of brain injury by measuring hemodynamic properties. We combined time
      shift voxel-mirrored homotopic connectivity analyses to investigate the
      alterations in homotopic connectivity in mesial temporal lobe epilepsy and
      assessed the value of applying this approach to epilepsy lateralization and the
      prediction of surgical outcomes in mesial temporal lobe epilepsy. MATERIALS AND
      METHODS: Resting-state functional MR imaging data were acquired from patients
      with unilateral mesial temporal lobe epilepsy (n=62) (31 left- and 31 right-side)
      and healthy controls (n=33). Dynamic interhemispheric homotopic architecture
      seeding from each hemisphere was individually calculated by 0, 1, 2, and 3
      repetition time time-shift voxel-mirrored homotopic connectivity. Voxel-mirrored
      homotopic connectivity maps were compared between the patient and control groups
      by using 1-way ANOVA for each time-shift condition, separately. Group comparisons
      were further performed on the laterality of voxel-mirrored homotopic connectivity
      in each time-shift condition. Finally, we correlated the interhemispheric
      homotopic connection to the surgical outcomes in a portion of the patients
      (n=20). RESULTS: The patients with mesial temporal lobe epilepsy showed decreased
      homotopic connectivity in the mesial temporal structures, temporal pole, and
      striatum. Alterations of the bihemispheric homotopic connectivity were
      lateralized along with delays in the time-shift in mesial temporal lobe epilepsy.
      The patients with unsuccessful surgical outcomes presented larger
      interhemispheric voxel-mirrored homotopic connectivity differences. CONCLUSIONS:
      This study showed whole patterns of dynamic alterations of interhemispheric
      homotopic connectivity in mesial temporal lobe epilepsy, extending the knowledge
      of abnormalities in interhemispheric connectivity in this condition. Time-shift
      voxel-mirrored homotopic connectivity has the potential for lateralization of
      unilateral mesial temporal lobe epilepsy and may have the capability of
      predicting surgical outcomes in this condition.

PMID- 24742803
TI  - Relative filling time delay based on CT perfusion source imaging: a simple method
      to predict outcome in acute ischemic stroke.
AB  - BACKGROUND AND PURPOSE: Collateral vessel status is strongly associated with
      clinical outcome in ischemic stroke but can be challenging to assess. The aim of
      this study was to develop a tomography perfusion source imaging-based assessment
      of collateral vessel status. MATERIALS AND METHODS: Consecutive patients with
      ischemic stroke who received intravenous thrombolysis or intra-arterial
      reperfusion therapy after CTP were retrospectively analyzed. In those with middle
      cerebral artery or internal carotid artery occlusion, CT perfusion source imaging
      was used to identify the relative filling time delay between the normal MCA
      Sylvian branches and those in the affected hemisphere. Receiver operating
      characteristic analysis and logistic regression were used to assess the
      association of the relative filling time delay with the 24-hour Alberta Stroke
      Program Early CT Score based on noncontrast CT and the 90-day modified Rankin
      Scale score. RESULTS: There were 217 patients treated in 2009-2011 who had CTP
      data, of whom 60 had MCA or ICA occlusion and 55 had 90-day mRS data. The
      intraclass correlation coefficient for relative filling time delay was 0.95.
      Relative filling time delay was correlated with 24-hour ASPECTS (Spearman rho=
      0.674; P<.001) and 90-day mRS score (rho=0.516, P<.01). Increased relative
      filling time delay was associated with poor radiologic outcome (ASPECTS, 0-7)
      (area under the curve=0.79, P<.001) and poor functional outcome (mRS score, 3-6)
      (area under the curve=0.77, P=.001). In multivariate logistic regression, the
      association of longer relative filling time delay with poor outcome remained
      significant, independent of age, sex, and baseline National Institutes of Health
      Stroke Scale score. CONCLUSIONS: Relative filling time delay is a useful
      independent predictor of clinical outcome after ischemic stroke.

PMID- 24742804
TI  - Comparison of the T2 relaxation time of the temporomandibular joint articular
      disk between patients with temporomandibular disorders and asymptomatic
      volunteers.
AB  - BACKGROUND AND PURPOSE: T2 relaxation time is a quantitative MR imaging parameter
      used to detect degenerated cartilage in the knee and lumbar intervertebral disks.
      We measured the T2 relaxation time of the articular disk of the temporomandibular
      joint in patients with temporomandibular disorders and asymptomatic volunteers to
      demonstrate an association between T2 relaxation time and temporomandibular
      disorder MR imaging findings. MATERIALS AND METHODS: One hundred forty-four
      patients with temporomandibular disorders and 17 volunteers were enrolled in this
      study. An 8-echo spin-echo sequence for measuring the T2 relaxation times was
      performed in the closed mouth position, and the T2 relaxation time of the entire
      articular disk was measured. Patients were classified according to the articular
      disk location and function, articular disk configuration, presence of joint
      effusion, osteoarthritis, and bone marrow abnormalities. RESULTS: The T2
      relaxation time of the entire articular disk was 29.3 +/- 3.8 ms in the volunteer
      group and 30.7 +/- 5.1 ms in the patient group (P = .177). When subgroups were
      analyzed, however, the T2 relaxation times of the entire articular disk in the
      anterior disk displacement without reduction group, the marked or extensive joint
      effusion group, the osteoarthritis-positive group, and the bone marrow
      abnormality-positive group were significantly longer than those in the volunteer
      group (P < .05). CONCLUSIONS: The T2 relaxation times of the articular disk of
      the temporomandibular joint in patients with progressive temporomandibular
      disorders were longer than those of healthy volunteers.

PMID- 24742805
TI  - Dress for success.

PMID- 24742806
TI  - Early basal ganglia hyperperfusion on CT perfusion in acute ischemic stroke: a
      marker of irreversible damage?
AB  - BACKGROUND AND PURPOSE: CT perfusion scans are often used in acute stroke
      evaluations. We aimed to assess the outcome of areas of basal ganglia
      hyperperfusion on CTP in patients with acute ischemic stroke. MATERIALS AND
      METHODS: We retrospectively reviewed the medical records and brain imaging of 139
      patients presenting with acute stroke who underwent CTP for consideration of
      endovascular recanalization. Hyperperfusion was assessed qualitatively and
      defined as a matched region of increased cerebral blood flow and cerebral blood
      volume. CTA was used to locate arterial occlusion. Follow-up imaging was used to
      determine whether regions of hyperperfusion at baseline became infarcted or
      developed hemorrhage. Angiographic imaging was assessed to determine the presence
      or absence of early venous opacification. RESULTS: Six patients (4.3%)
      demonstrated hyperperfusion in the basal ganglia of the affected side (4 in the
      lenticular nucleus and 2 in the caudate). In all cases, the area of
      hyperperfusion ultimately proved to be infarcted. All patients had received
      intravenous thrombolysis before the CTP. CTA at the time of CTP showed middle or
      distal M1 occlusion but patency of the proximal M1 and A1 segments. Intracranial
      hemorrhage was noted in 2 of these 6 patients at follow-up. CONCLUSIONS: Acute
      basal ganglia hyperperfusion in patients with stroke may indicate nonviable
      parenchyma and risk of hemorrhagic conversion.

PMID- 24742807
TI  - Transarterial onyx embolization of cranial dural arteriovenous fistulas: long
      term follow-up.
AB  - BACKGROUND AND PURPOSE: Endovascular therapy with liquid embolic agents is a
      common treatment strategy for cranial dural arteriovenous fistulas. This study
      evaluated the long-term effectiveness of transarterial Onyx as the single embolic
      agent for curative embolization of noncavernous cranial dural arteriovenous
      fistulas. MATERIALS AND METHODS: We performed a retrospective review of 40
      consecutive patients with 41 cranial dural arteriovenous fistulas treated between
      March 2006 and June 2012 by using transarterial Onyx embolization with intent to
      cure. The mean age was 57 years; one-third presented with intracranial
      hemorrhage. Most (85%) had cortical venous drainage. Once angiographic cure was
      achieved, long-term treatment effectiveness was assessed with DSA and clinical
      follow-up. RESULTS: Forty-nine embolization sessions were performed; 85% of
      cranial dural arteriovenous fistulas were treated in a single session. The
      immediate angiographic cure rate was 95%. The permanent neurologic complication
      rate was 2% (mild facial palsy). Thirty-five of the 38 patients with initial cure
      underwent short-term follow-up DSA (median, 4 months). The short-term recurrence
      rate was only 6% (2/35). All patients with occlusion at short-term DSA undergoing
      long-term DSA (median, 28 months) had durable occlusion. No patient with long
      term clinical follow-up (total, 117 patient-years; median, 45 months) experienced
      hemorrhage. CONCLUSIONS: Transarterial embolization with Onyx as the single
      embolic agent results in durable long-term cure of noncavernous cranial dural
      arteriovenous fistulas. Recurrence rates are low on short-term follow-up, and all
      patients with angiographic occlusion on short-term DSA follow-up have experienced
      a durable long-term cure. Thus, angiographic cure should be defined at short-term
      follow-up angiography instead of at the end of the final embolization session.
      Finally, long-term DSA follow-up may not be necessary if occlusion is
      demonstrated on short-term angiographic follow-up.

PMID- 24742808
TI  - Clinical significance of an increased cochlear 3D fluid-attenuated inversion
      recovery signal intensity on an MR imaging examination in patients with acoustic
      neuroma.
AB  - BACKGROUND AND PURPOSE: The increased cochlear signal on FLAIR images in patients
      with acoustic neuroma is explained by an increased concentration of protein in
      the perilymphatic space. However, there is still debate whether there is a
      correlation between the increased cochlear FLAIR signal and the degree of hearing
      disturbance in patients with acoustic neuroma. Our aim was to investigate the
      clinical significance of an increased cochlear 3D FLAIR signal in patients with
      acoustic neuroma according to acoustic neuroma extent in a large patient cohort.
      MATERIALS AND METHODS: This retrospective study enrolled 102 patients with
      acoustic neuroma, who were divided into 2 groups based on tumor location; 22
      tumors were confined to the internal auditory canal and 80 extended to the
      cerebellopontine angle cistern. Pure tone audiometry results and hearing symptoms
      were obtained from medical records. The relative signal intensity of the entire
      cochlea to the corresponding brain stem was calculated by placing regions of
      interest on 3D FLAIR images. Statistical analysis was performed to compare the
      cochlear relative signal intensity between the internal auditory canal acoustic
      neuroma and the cerebellopontine angle acoustic neuroma. The correlation between
      the cochlear relative signal intensity and the presence of hearing symptoms or
      the pure tone audiometry results was investigated. RESULTS: The internal auditory
      canal acoustic neuroma cochlea had a significantly lower relative signal
      intensity than the cerebellopontine angle acoustic neuroma cochlea (0.42+/-0.15
      versus 0.60+/-0.17, P<.001). The relative signal intensity correlated with the
      audiometric findings in patients with internal auditory canal acoustic neuroma
      (r=0.471, P=.027) but not in patients with cerebellopontine angle acoustic
      neuroma (P=.427). Neither internal auditory canal acoustic neuroma nor
      cerebellopontine angle acoustic neuroma showed significant relative signal
      intensity differences, regardless of the presence of hearing symptoms (P>.5).
      CONCLUSIONS: The cochlear signal on FLAIR images may be an additional parameter
      to use when monitoring the degree of functional impairment during follow-up of
      patients with small acoustic neuromas confined to the internal auditory canals.

PMID- 24742809
TI  - Various MRS application tools for Alzheimer disease and mild cognitive
      impairment.
AB  - MR spectroscopy is a noninvasive technique that allows the detection of several
      naturally occurring compounds (metabolites) from well-defined regions of interest
      within the human brain. Alzheimer disease, a progressive neurodegenerative
      disorder, is the most common cause of dementia in the elderly. During the past 20
      years, multiple studies have been performed on MR spectroscopy in patients with
      both mild cognitive impairment and Alzheimer disease. Generally, MR spectroscopy
      studies have found decreased N-acetylaspartate and increased myo-inositol in both
      patients with mild cognitive impairment and Alzheimer disease, with greater
      changes in Alzheimer disease than in mild cognitive impairment. This review
      summarizes the information content of proton brain MR spectroscopy and its
      related technical aspects, as well as applications of MR spectroscopy to mild
      cognitive impairment and Alzheimer disease. While MR spectroscopy may have some
      value in the differential diagnosis of dementias and assessing prognosis, more
      likely its role in the near future will be predominantly as a tool for monitoring
      disease response or progression in treatment trials. More work is needed to
      evaluate the role of MR spectroscopy as a biomarker in Alzheimer disease and its
      relationship to other imaging modalities.

PMID- 24742810
TI  - Quantitative 7T phase imaging in premanifest Huntington disease.
AB  - BACKGROUND AND PURPOSE: In vivo MR imaging and postmortem neuropathologic studies
      have demonstrated elevated iron concentration and atrophy within the striatum of
      patients with Huntington disease, implicating neuronal loss and iron accumulation
      in the pathogenesis of this neurodegenerative disorder. We used 7T MR imaging to
      determine whether quantitative phase, a measurement that reflects both iron
      content and tissue microstructure, is altered in subjects with premanifest
      Huntington disease. MATERIALS AND METHODS: Local field shift, calculated from 7T
      MR phase images, was quantified in 13 subjects with premanifest Huntington
      disease and 13 age- and sex-matched controls. All participants underwent 3T and
      7T MR imaging, including volumetric T1 and 7T gradient recalled-echo sequences.
      Local field shift maps were created from 7T phase data and registered to caudate
      ROIs automatically parcellated from the 3T T1 images. Huntington disease-specific
      disease burden and neurocognitive and motor evaluations were also performed and
      compared with local field shift. RESULTS: Subjects with premanifest Huntington
      disease had smaller caudate volume and higher local field shift than controls. A
      significant correlation between these measurements was not detected, and
      prediction accuracy for disease state improved with inclusion of both variables.
      A positive correlation between local field shift and genetic disease burden was
      also found, and there was a trend toward significant correlations between local
      field shift and neurocognitive tests of working memory and executive function.
      CONCLUSIONS: Subjects with premanifest Huntington disease exhibit differences in
      7T MR imaging phase within the caudate nuclei that correlate with genetic disease
      burden and trend with neurocognitive assessments. Ultra-high-field MR imaging of
      quantitative phase may be a useful approach for monitoring neurodegeneration in
      premanifest Huntington disease.

PMID- 24742811
TI  - Field validation of secondary data sources for enumerating retail tobacco outlets
      in a state without tobacco outlet licensing.
AB  - Identifying tobacco retail outlets for U.S. FDA compliance checks or calculating
      tobacco outlet density is difficult in the 13 States without tobacco retail
      licensing or where licensing lists are unavailable for research. This study uses
      primary data collection to identify tobacco outlets in three counties in a non
      licensing state and validate two commercial secondary data sources. We calculated
      sensitivity and positive predictive values (PPV) to examine the evidence of
      validity for two secondary data sources, and conducted a geospatial analysis to
      determine correct allocation to census tract. ReferenceUSA had almost perfect
      sensitivity (0.82) while Dun & Bradstreet (D&B) had substantial sensitivity
      (0.69) for identifying tobacco outlets; combined, sensitivity improved to 0.89.
      D&B identified fewer "false positives" with a PPV of 0.82 compared to 0.71 for
      ReferenceUSA. More than 90% of the outlets identified by ReferenceUSA were
      geocoded to the correct census tract. Combining two commercial data sources
      resulted in enumeration of nearly 90% of tobacco outlets in a three county area.
      Commercial databases appear to provide a reasonably accurate way to identify
      tobacco outlets for enforcement operations and density estimation. 

PMID- 24742812
TI  - Trends in the prevalence of major cardiovascular disease risk factors among
      Korean adults: results from the Korea National Health and Nutrition Examination
      Survey, 1998-2012.
AB  - BACKGROUND: Mortality from coronary heart disease in Korea has increased
      continuously, but there are few comprehensive national data on trend in the
      prevalence of risk factors for cardiovascular disease in this population. We
      examined the trends in the prevalence of major risk factors for cardiovascular
      disease, including smoking, obesity, hypertension, diabetes, and
      hypercholesterolemia, from 1998 through 2012 in a representative Korean
      population. METHODS: Using data from the Korea National Health and Nutrition
      Examination Survey I (1998) to V (2010-2012), we selected the adults aged>=30 yr
      who participated in both a health examination and health interview survey.
      RESULTS: From 1998 to 2012, significant decrease in the prevalence of
      hypertension was observed in both men (32.5 to 31.5%) and women (26.9 to 24.3%).
      Smoking rates decreased only in men (65.1 to 47.0%), whereas the prevalence of
      diabetes did not change over time. Conversely, the prevalence of
      hypercholesterolemia significantly increased from 7.2% to 12.6% for men and from
      8.4% to 14.9% for women, whereas the rates of awareness and treatment for
      hypercholesterolemia were relatively lower than that of hypertension and
      diabetes. During the period, prevalence of obesity significantly increased from
      26.8% to 38.1% only in men. CONCLUSIONS: The increased prevalence of
      hypercholesterolemia and obesity may have contributed to the increasing trend in
      the mortality from coronary heart disease in Korea. Further population-based
      surveillance of blood cholesterol levels and obesity needs to be performed, and
      national strategies for improvement of these factors should be established in
      Korea.

PMID- 24742813
TI  - Bidirectional effect of serum amyloid A on plaque stability.

PMID- 24742814
TI  - Utility of post-mortem lipid levels in fatal premature CAD: an autopsy study.

PMID- 24742815
TI  - Neutral sphingomyelinase inhibition decreases ER stress-mediated apoptosis and
      inducible nitric oxide synthase in retinal pigment epithelial cells.
AB  - Endoplasmic reticulum (ER) stress and excessive nitric oxide production via the
      induction of inducible nitric oxide synthase (NOS2) have been implicated in the
      pathogenesis of ocular diseases characterized by retinal degeneration. Previous
      studies have revealed the sphingomyelinase/ceramide pathway in the regulation of
      NOS2 induction. Thus, the objective of this study was to determine the activity
      of the sphingomyelinase/ceramide pathway, assess nitric oxide production, and
      examine apoptosis in human retinal pigment epithelial (RPE) cells undergoing ER
      stress. Sphingomyelinase (SMase) activity; nuclear factor kappaB (NF-kappaB)
      activation; NOS2, nitrite/nitrate, and nitrotyrosine levels; and apoptosis were
      determined in cultured human RPE cell lines subjected to ER stress via exposure
      to tunicamycin. Induction of ER stress was confirmed by increased intracellular
      levels of ER stress markers including phosphorylated PKR-like ER kinase, C/EBP
      homologous protein, and 78-kDa glucose-regulated protein. ER stress increased
      nuclear translocation of NF-kappaB, NOS2 expression, nitrite/nitrate levels, and
      nitrotyrosine formation and caused apoptosis in RPE cell lines. Inhibition of
      neutral SMase (N-SMase) activity via GW 4869 treatment caused a significant
      reduction in nuclear translocation of NF-kappaB, NOS2 expression, nitrite/nitrate
      levels, nitrotyrosine formation, and apoptosis in ER-stressed RPE cells. In
      conclusion, N-SMase inhibition reduced nitrative stress and apoptosis in RPE
      cells undergoing ER stress. Obtained data suggest that NOS2 can be regulated by N
      SMase in RPE cells experiencing ER stress. 

PMID- 24742816
TI  - Dimerization of visinin-like protein 1 is regulated by oxidative stress and
      calcium and is a pathological hallmark of amyotrophic lateral sclerosis.
AB  - Redox control of proteins that form disulfide bonds upon oxidative challenge is
      an emerging topic in the physiological and pathophysiological regulation of
      protein function. We have investigated the role of the neuronal calcium sensor
      protein visinin-like protein 1 (VILIP-1) as a novel redox sensor in a cellular
      system. We have found oxidative stress to trigger dimerization of VILIP-1 within
      a cellular environment and identified thioredoxin reductase as responsible for
      facilitating the remonomerization of the dimeric protein. Dimerization is
      modulated by calcium and not dependent on the myristoylation of VILIP-1.
      Furthermore, we show by site-directed mutagenesis that dimerization is
      exclusively mediated by Cys187. As a functional consequence, VILIP-1 dimerization
      modulates the sensitivity of cells to an oxidative challenge. We have
      investigated whether dimerization of VILIP-1 occurs in two different animal
      models of amyotrophic lateral sclerosis (ALS) and detected soluble VILIP-1 dimers
      to be significantly enriched in the spinal cord from phenotypic disease onset
      onwards. Moreover, VILIP-1 is part of the ALS-specific protein aggregates. We
      show for the first time that the C-terminus of VILIP-1, containing Cys187, might
      represent a novel redox-sensitive motif and that VILIP-1 dimerization and
      aggregation are hallmarks of ALS. This suggests that VILIP-1 dimers play a
      functional role in integrating the cytosolic calcium concentration and the
      oxidative status of the cell. Furthermore, a loss of VILIP-1 function owing to
      protein aggregation in ALS could be relevant in the pathophysiology of the
      disease. 

PMID- 24742817
TI  - Respiratory sensitizer hexamethylene diisocyanate inhibits SOD 1 and induces ERK
      dependent detoxifying and maturation pathways in dendritic-like cells.
AB  - Respiratory allergy to low-molecular-weight chemicals is a current concern in the
      context of occupational health, and a certified method to identify respiratory
      allergens is still under investigation. The aim of this work was to unveil some
      of the poorly understood initial molecular events and toxicity pathways
      underlying respiratory sensitization, which might be crucial to disclosing the
      key building blocks of new testing strategies and may contribute to the
      development of a valid in vitro method for the identification of respiratory
      allergens. Immortalized human dendritic cell (DC)-like THP-1 cells were exposed
      to the respiratory allergen hexamethylene diisocyanate (HDI) for 6h, and the
      activation of several signaling pathways was analyzed. Mitochondrial membrane
      potential (MMP) alterations, superoxide anion (O2(-)) production, and gene
      expression modulation in HDI-treated cells were also evaluated. According to our
      results, HDI induces O2(-) increase (P < 0.001) through enzymatic inhibition of
      cytoplasmic superoxide dismutase 1 (P < 0.05), which might reduce MMP, further
      leading to mitochondrial O2(-) production. Increased O2(-) levels promote ERK
      phosphorylation (approx sixfold compared to control; P < 0.001) and downstream
      transcriptional increase of several genes: HMOX1 (P < 0.05), involved in the
      protection of chemical reactive species; MDR1 (P < 0.01), responsible for the
      efflux of xenobiotics in the cell; and CD83 (P < 0.05), a DC maturation marker.
      These results raise new perspectives on the action of respiratory allergens in
      DCs and point out key molecular events that are crucial for the development of
      the so-called adverse outcome pathways, particularly regarding O2(-) increase
      through enzymatic inhibition, and important for ERK activation. Furthermore, our
      results highlight the role of ERK signaling, but not p38 MAPK, in the activation
      of vital mechanisms in cells exposed to a respiratory allergen, such as cell
      detoxification, migration, and maturation. 

PMID- 24742818
TI  - Lowering of oxidative stress improves endothelial function in healthy subjects
      with habitually low intake of fruit and vegetables: a randomized controlled trial
      of antioxidant- and polyphenol-rich blackcurrant juice.
AB  - Inadequate intake of the recommended five-a-day fruit and vegetable portions
      might contribute to increased cardiovascular disease risk. We assessed the
      effects of dietary intake of a blackcurrant juice drink, rich in vitamin C and
      polyphenols, on oxidative stress and vascular function. This was a double-blind,
      placebo-controlled, parallel group study of 66 healthy adults who habitually
      consume <2 portions of fruit and vegetables per day. Participants were randomly
      allocated to consume 250ml of placebo (flavored water) or low or high
      blackcurrant juice drink four times a day for 6 weeks. Flow-mediated dilation
      (FMD) and plasma concentrations of F2-isoprostanes and vitamin C were measured.
      In the high blackcurrant juice drink group FMD increased significantly (5.8+/-3.1
      to 6.9+/-3.1%, P=0.022) compared with the placebo group (6.0+/-2.2 to 5.1+/
      2.4%). Plasma vitamin C concentration increased significantly in the low (38.6+/
      17.6 to 49.4+/-21.0umol/L, P<0.001) and high (34.6+/-20.4 to 73.8+/-23.3umol/L,
      P<0.001) blackcurrant juice drink groups compared with the placebo group (38.1+/
      21.0 to 29.0+/-17.6umol/L). F2-isoprostane concentrations were significantly
      lower in the high blackcurrant juice drink group (225+/-64pg/ml) compared with
      the low blackcurrant juice drink (257+/-69pg/ml, P=0.002) and placebo group
      (254+/-59pg/ml, P=0.003). At follow-up, changes in plasma vitamin C correlated
      significantly with changes in FMD (r=0.308, P=0.044). Consumption of blackcurrant
      juice drink high in vitamin C and polyphenols can decrease oxidative stress and
      improve vascular health in individuals with habitually low dietary fruit and
      vegetable intake. 

PMID- 24742819
TI  - Separating natural from anthropogenic causes of impairment in Zebra mussel
      (Dreissena polymorpha) populations living across a pollution gradient.
AB  - The relationship between the reproductive stage, the total lipid content and
      eight broadly used biochemical stress responses were used to assess seasonal and
      pollutant effects across eleven different zebra mussel (Dreissena polymorpha)
      populations from the Ebro and Mijares river basin, Spain. Biochemical markers
      included superoxide dismutase (SOD), catalase (CAT), glutathione (GSH),
      glutathione S transferase (GST), multixenobiotic transporter activity (MXR),
      lactate dehydrogenase (LDH), lipid peroxidation (LPO) and single strand DNA
      breaks. Principal component analyses of zebra mussel responses across an annual
      cycle, showed a marked gonad stage component in total lipid content and
      biochemical responses. The same response pattern was observed across the
      populations sampled along a broad geographical and pollution gradient. Population
      differences on the gonad developmental stage were highly correlated with most of
      the measured responses and unrelated with the pollution gradient. Conversely,
      bioaccumulation of organic and inorganic contaminant residues was more related to
      pollution sources than with the reproductive cycle. These results indicate that
      the reproductive cycle is the major factor affecting the temporal and spatial
      variation of the studied markers in D. polymorpha. 

PMID- 24742820
TI  - The potential toxicity of copper nanoparticles and copper sulphate on juvenile
      Epinephelus coioides.
AB  - Copper nanoparticles (Cu-NPs) were widely used in various industrial and
      commercial applications. In this study the effects of Cu-NPs and soluble Cu were
      investigated on juvenile Epinephelus coioides. The fish were exposed in
      triplicate to control, 20 or 100MUgCuL(-1) as either copper sulphate (CuSO4) or
      Cu-NPs in a semi-static aqueous culture for 25 days. The growth parameters were
      significantly lower at 100MUgCuL(-1) as CuSO4 or Cu-NPs treatment compared to
      control. Time-dependent Cu accumulation in all tissues increased with increasing
      the Cu dose. The percentage of total Cu found in remaining tissues (head, bones,
      fins, etc.) decreased more in the CuSO4 than Cu-NPs treatment after 25 days, but
      increased in all other tissues (especially in liver). Compared with the control,
      either Cu-NPs or CuSO4 induced higher malonaldehyde concentration in tissues by
      overwhelming total superoxide dismutase activity, total glutathione concentration
      and Na(+)/K(+)-ATPase activity, but the opposite results were recorded for the
      brain. With increasing the CuSO4 or Cu-NPs dose, apoptosis was exacerbated in the
      liver and gills, more so by CuSO4 than Cu-NPs. Overall, these findings showed
      that Cu-NPs had the toxic effects similar to dissolved Cu; hence, Cu-NPs need to
      be included in the assessment of toxicological impacts in the aquatic
      environment. 

PMID- 24742821
TI  - What do experts think we should do to achieve brain health?

PMID- 24742822
TI  - [The Death of the Virgin. Master of the Sisla. Prado Museum, Madrid].

PMID- 24742823
TI  - MET aberrations and c-MET inhibitors in patients with gastric and esophageal
      cancers in a phase I unit.
AB  - We sought to investigate the demographics and tumor-associated features in
      patients with gastroesophageal (GE) malignancies referred to our Phase I Program
      who had formalin-fixed, paraffin-embedded tissue from archival or new biopsies
      tested for MET mutation and/or amplification. MET amplification was found in 5 of
      76 (6.6%) patients (3/34 [8.8%] esophageal, 2/26 [7.7%] gastric and none in 22
      gastroesophageal junction cancers). The only MET mutation detected in 3 of 41
      (7.3%) patients was N375S. No demographic and histologic characteristics were
      associated with specific MET abnormalities. Median overall survival was 3 and 5
      months for patients with and without a MET alteration, respectively (hazard ratio
      [HR] = 2.1; 95% CI, 0.8 to 5.5; P=.14). Sixteen of 81 (20%) patients were
      enrolled in a c-MET inhibitor trial. Best responses were stable disease in 3
      patients (19%), including a patient with esophageal adenocarcinoma that remained
      on the trial for 9.9 months (wild-type for MET abnormality). All tumors with MET
      abnormality (n=3) progressed on a c-MET inhibitor in fewer than 2 months. In
      conclusion, MET abnormalities can be found in a small group of patients with GE
      adenocarcinoma and further studies are necessary to better characterize the
      prognostic and predictive impact of MET alterations. 

PMID- 24742825
TI  - Protein motions and the activation of the CH bond catalyzed by dihydrofolate
      reductase.
AB  - The role of protein motions in enzymatic CH->C transfer is an area of great
      contemporary debate. An effective tool in probing such a role is the temperature
      dependence of the intrinsic kinetic isotope effects for the enzyme-catalyzed
      reaction. The outcome of those experiments is interpreted within the context of
      phenomenological Marcus-like models of hydrogen tunneling. The current review
      focuses on recent studies of dihydrofolate reductase (DHFR) and how the role of
      protein motions in the catalyzed reaction has been demonstrated. The motions in
      DHFR are controlled by local effects of active site residues, global effects
      involving remote residues across the enzyme and appear to be preserved during the
      evolution of the enzyme from bacteria to human. 

PMID- 24742826
TI  - Outcome of male breast cancer: a matched single-institution series.
AB  - BACKGROUND: Breast cancer occurs rarely in men, accounting for approximately 1%
      of all breast carcinomas. Data on prognosis principally derive from retrospective
      studies and from extrapolation of female breast cancer series. PATIENTS AND
      METHODS: A total of 99 men with invasive breast cancer were matched with 198
      women with breast cancer who had surgery at the same institution from 1999 to
      2010. Matching variables were year of surgery, age, primary tumor size, nodal
      involvement, hormone receptor status, status of HER2 (human epidermal growth
      factor receptor 2 [ERBB2]), Ki-67, and grade. Median follow-up was 8.6 years.
      RESULTS: Disease-free survival (DFS) was significantly poorer in the men (10-year
      DFS, 51.7% vs. 66.5%; hazard ratio [HR], 1.79; 95% CI, 1.19-2.68; P = .004).
      Similar results were observed for overall survival (OS) (10-year OS, 70.7% vs.
      84.2%; HR, 1.79; 95% CI, 1.01-3.15; P = .043). The cumulative incidence of death
      for causes not related to the primary breast cancer was significantly higher for
      men than for women (HR, 2.87; 95% CI, 1.58-5.22; P = .001), whereas the breast
      cancer-specific survival (BCSS) was similar between the 2 groups (10-year BCSS,
      81.5% vs. 88%; HR, 1.27; 95% CI, 0.62-2.59; P = .517). CONCLUSION: This
      comparative series found that men with breast cancer had a poorer DFS and OS when
      compared with women. The men also had a higher risk of contralateral tumors and
      second primaries. Appropriate counseling, surveillance, and prevention are
      recommended to improve survival for these individuals.

PMID- 24742827
TI  - Ferritin heavy chain in triple negative breast cancer: a favorable prognostic
      marker that relates to a cluster of differentiation 8 positive (CD8+) effector T
      cell response.
AB  - Ferritin heavy chain (FTH1) is a 21-kDa subunit of the ferritin complex, known
      for its role in iron metabolism, and which has recently been identified as a
      favorable prognostic protein for triple negative breast cancer (TNBC) patients.
      Currently, it is not well understood how FTH1 contributes to an anti-tumor
      response. Here, we explored whether expression and cellular compartmentalization
      of FTH1 correlates to an effective immune response in TNBC patients. Analysis of
      the tumor tissue transcriptome, complemented with in silico pathway analysis,
      revealed that FTH1 was an integral part of an immunomodulatory network of
      cytokine signaling, adaptive immunity, and cell death. These findings were
      confirmed using mass spectrometry (MS)-derived proteomic data, and
      immunohistochemical staining of tissue microarrays. We observed that FTH1 is
      localized in both the cytoplasm and/or nucleus of cancer cells. However, high
      cytoplasmic (c) FTH1 was associated with favorable prognosis (Log-rank p =
      0.001), whereas nuclear (n) FTH1 staining was associated with adverse prognosis
      (Log-rank p = 0.019). cFTH1 staining significantly correlated with total FTH1
      expression in TNBC tissue samples, as measured by MS analysis (Rs = 0.473, p =
      0.0007), but nFTH1 staining did not (Rs = 0.197, p = 0.1801). Notably, IFN gamma
      producing CD8+ effector T cells, but not CD4+ T cells, were preferentially
      enriched in tumors with high expression of cFTH1 (p = 0.02). Collectively, our
      data provide evidence toward new immune regulatory properties of FTH1 in TNBC,
      which may facilitate development of novel therapeutic targets. 

PMID- 24742828
TI  - Correlation of ALOX15 expression with eosinophilic or reflux esophagitis in a
      cohort of pediatric patients with esophageal eosinophilia.
AB  - The differential diagnosis between eosinophilic esophagitis (EoE) and
      gastroesophageal reflux disease (GERD) is often challenging. We recently showed
      that the ALOX15 protein is expressed in 95% of esophageal biopsies from patients
      with a definitive diagnosis of EoE. Here we correlated ALOX15 expression with the
      clinical classification of EoE or GERD in a cohort of consecutive pediatric
      patients (n = 62) with at least 1 esophageal biopsy containing at least 15
      eosinophils per high-power field (eos/HPF). The patients were categorized into
      the following groups: (1) at least 15 eos/HPF in the distal esophagus only (n =
      24), (2) at least 15 eos/HPF in the proximal esophagus only (n = 5), and (3) at
      least 15 eos/HPF in the distal and proximal biopsies (n = 33). Control groups
      included patients with GERD with biopsies containing 6 to 15 eos/HPF (n = 9),
      patients with GERD with 5 eos/HPF or less (n = 15), patients with candida
      esophagitis (n = 15), and patients with normal biopsies (n = 15). ALOX15 was
      positive in 90.5% of patients with EoE (13/16 in group 1, 4/4 in group 2, 31/33
      in group 3) versus 44% of patients with GERD (4/8 in group 1, 0/1 in group 2, and
      0/0 in group 3), 2 of 9 (22%) of patients with 6 to 15 eos/HPF, and was negative
      in all patients with GERD with biopsies containing 5 eos/HPF or less, all
      patients with candida esophagitis, and all normal controls. In conclusion, ALOX15
      is a sensitive marker of EoE; however, subpopulations of patients with GERD with
      >5 eos/HPF also express ALOX15. Positive ALOX15 expression is more prevalent in
      EoE than in GERD and may prove to be a useful diagnostic marker in patients with
      discrepant biopsy findings between the proximal and distal esophagus. 

PMID- 24742829
TI  - USP6 gene rearrangements occur preferentially in giant cell reparative granulomas
      of the hands and feet but not in gnathic location.
AB  - Giant cell reparative granulomas (GCRGs) are lytic lesions that occur
      predominantly in the gnathic bones and occasionally in the small bones of the
      hands and feet. They are morphologically indistinguishable from, and are regarded
      as synonymous with, solid variant of aneurysmal bone cysts (ABC) in extragnathic
      sites. Identification of USP6 gene rearrangements in primary ABC has made
      possible investigating potential pathogenetic relationships with other
      morphologic mimics. USP6 gene alterations in giant cell-rich lesions (GCRG/ABC)
      of small bones of the hands and feet have not been previously studied. We
      investigated USP6 gene alterations in a group of 9 giant cell-rich lesions of the
      hands and feet and compared the findings with morphologically similar lesions
      including 8 gnathic GCRGs, 22 primary ABCs, 8 giant cell tumors of bone, and 2
      brown tumors of hyperparathyroidism. Overall, there were 49 samples from 48
      patients including 26 females and 22 males. Of the 9 lesions of the hands and
      feet, 8 (89%) showed USP6 gene rearrangements, whereas no abnormalities were
      identified in the 8 gnathic GCRGs, 2 brown tumors, or 8 giant cell tumors of
      bone. Of the 22 primary ABCs, 13 (59%) showed USP6 gene rearrangements. In
      conclusion, most GCRGs of the hands and feet represent true ABCs and should be
      classified as such. The terminology of GCRG should be limited to lesions from
      gnathic location. Fluorescence in situ hybridization for USP6 break-apart is a
      useful ancillary tool in the diagnosis of primary ABCs and distinguishing them
      from GCRGs and other morphologically similar lesions. 

PMID- 24742830
TI  - Detection of Ophiocordyceps sinensis in the roots of plants in alpine meadows by
      nested-touchdown polymerase chain reaction.
AB  - Ophiocordyceps sinensis, one of the most important income sources of rural
      Tibetan families, is an entomopathogenic fungus that parasitizes the ghost moth
      Thitarodes larvae, which live in alpine meadows on the Tibetan Plateau and in the
      Himalayas. The annual yield of O. sinensis has gradually declined in recent
      years. However, there is no effective method to sustain or increase the yield of
      O. sinensis artificially because the life cycle of the O. sinensis anamorph
      remains unclear. Here we detected O. sinensis in alpine plant roots by nested
      touchdown polymerase chain reaction (PCR). Forty-two alpine plant species were
      screened. The roots from 23 alpine plant species (54.76%) tested positive
      including 13 families and 18 genera. The detection results indicate that O.
      sinensis is present in the plant roots during the anamorph life cycle, to deal
      with harsh conditions in alpine habitats and have an increased opportunity to
      infect the larvae. The finding provides new information regarding the biology and
      ecology of O. sinensis that may be used to sustain this valuable resource.

PMID- 24742831
TI  - Zearalenone detoxification by zearalenone hydrolase is important for the
      antagonistic ability of Clonostachys rosea against mycotoxigenic Fusarium
      graminearum.
AB  - The fungus Clonostachys rosea is antagonistic against plant pathogens, including
      Fusarium graminearum, which produces the oestrogenic mycotoxin zearalenone (ZEA).
      ZEA inhibits other fungi, and C. rosea can detoxify ZEA through the enzyme
      zearalenone lactonohydrolase (ZHD101). As the relevance of ZEA detoxification for
      biocontrol is unknown, we studied regulation and function of ZHD101 in C. rosea.
      Quantitative reverse-transcription PCR revealed zhd101 gene expression in all
      conditions studied and demonstrated dose-dependent induction by ZEA. Known
      inducers of the Polyketide Synthase pathway did not induce zhd101 expression,
      suggesting specificity of the enzyme towards ZEA. To assess the role of ZHD101
      during biocontrol interactions, we generated two Deltazhd101 mutants incapable of
      ZEA-detoxification and confirmed their defect in degrading ZEA by HPLC. The
      Deltazhd101 mutants displayed a lower in vitro ability to inhibit growth of the
      ZEA-producing F. graminearum (strain 1104-14) compared to the wild type. In
      contrast, all three C. rosea strains equally inhibited growth of the F.
      graminearum mutant (DeltaPKS4), which is impaired in ZEA-production. Furthermore,
      the Deltazhd101 mutants failed to protect wheat seedlings against foot rot caused
      by the ZEA-producing F. graminearum. These data show that ZEA detoxification by
      ZHD101 is important for the biocontrol ability of C. rosea against F.
      graminearum. 

PMID- 24742833
TI  - Significance of the class II hydrophobin FgHyd5p for the life cycle of Fusarium
      graminearum.
AB  - Hydrophobins are small secreted proteins ubiquitously found in filamentous fungi.
      Some hydrophobins were shown to have functions in fungal development, while
      others lack known function. Class II hydrophobins from Fusarium graminearum and
      Fusarium culmorum are characterized by formation of low stability aggregates and
      their solubility in organic solvents. They are economically relevant to the
      brewing industry because they can induce beer gushing. Since cellular functions
      of Hyd5p's are still unknown, we analyzed the influence of FgHyd5p on growth and
      morphology of F. graminearum using FgDeltahyd5 knock-out mutants expressing sGFP
      under the control of the hyd5 promoter and compared them with the performance of
      the parent wild type strain. Results demonstrate that FgHyd5p does not affect the
      colony and hyphal morphology. FgHyd5p affects the hydrophobicity of aerial
      mycelia but had no obvious function in penetration of hyphae through the water
      air interface. The hydrophobin affects the morphology of conidia, but not their
      fitness. Different sources of carbon and nitrogen as well as different pH have no
      effect on the expression of the hyd5 gene, which was demonstrated to be expressed
      upon growth of F. graminearum on hydrophobic surfaces. 

PMID- 24742832
TI  - Genealogical concordance phylogenetic species recognition in the Fusarium
      oxysporum species complex.
AB  - Fusarium oxysporum is an important plant and human pathogenic ascomycetous group,
      with near ubiquity in agricultural and non-cultivated ecosystems. Phylogenetic
      evidence suggests that F. oxysporum is a complex of multiple morphologically
      cryptic species. Species boundaries and limits of genetic exchange within this
      complex are poorly defined, largely due to the absence of a sexual state and the
      paucity of morphological characters. This study determined species boundaries
      within the F. oxysporum species complex using Genealogical Concordance
      Phylogenetic Species Recognition (GCPSR) with eight protein coding loci. GCPSR
      criteria were used firstly to identify independent evolutionary lineages (IEL),
      which were subsequently collapsed into phylogenetic species. Seventeen IELs were
      initially identified resulting in the recognition of two phylogenetic species.
      Further evidence supporting this delineation is discussed. 

PMID- 24742834
TI  - Dill (Anethum graveolens L.) seed essential oil induces Candida albicans
      apoptosis in a metacaspase-dependent manner.
AB  - Dill (Anethum graveolens L.) has been used in traditional Uighur medicine for its
      various pharmacological activities. Previous studies have suggested that dill
      seed essential oil (DSEO) has anti-Candida potential and the mechanism of its
      action also has been studied. Our study examined whether DSEO induces apoptosis
      in the human pathogen Candida albicans ATCC 64550. Our results indicate that C.
      albicans ATCC 64550 cells treated with DSEO show some typical apoptosis
      characters, such as decrease in adenosine triphosphatase (ATPase) activity,
      chromatin condensation, nuclear fragmentation, and phosphatidylserine (PS)
      exposure. The DSEO promoted cytochrome c (cyt c) release and metacaspase
      activation, which resulted in C. albicans ATCC 64550 apoptosis. L-cysteine
      prevented the DSEO-induced nuclear fragmentation, PS externalization, and
      metacaspase activation, thus indicating that the reactive oxygen species (ROS) is
      an important mediator of DSEO-induced apoptosis. To our knowledge, this study is
      the first to report the induction of apoptosis of this pathogen with concomitant
      metacaspase activation by DSEO.

PMID- 24742835
TI  - A single nucleotide polymorphism in the translation elongation factor 1alpha gene
      correlates with the ability to produce fumonisin in Japanese Fusarium fujikuroi.
AB  - PCR-RFLP based on the translation elongation factor 1alpha (TEF) gene was
      developed to identify Fusarium fujikuroi in the Fusarium (Gibberella) fujikuroi
      species complex. Ninety-three strains, most of which were obtained from various
      sources in Japan, were identified as F. fujikuroi and their capability to produce
      fumonisin was investigated using an in vitro assay. Fumonisin production was
      detected in 50 strains isolated from maize, strawberry, wheat, and rice, whereas
      it was undetectable in 43 strains derived from rice seeds and rice seedlings
      carrying the bakanae disease, and from unknown sources. A single nucleotide
      polymorphism in the TEF gene (T618G) correlated with the ability to synthesize
      fumonisin.

PMID- 24742836
TI  - Functional analysis of a melanin biosynthetic gene using RNAi-mediated gene
      silencing in Rosellinia necatrix.
AB  - Rosellinia necatrix causes white root rot in a wide range of fruit trees and
      persists for extended periods as pseudosclerotia on root debris. However, the
      pathogenesis of this disease has yet to be clarified. The functions of
      endogeneous target genes have not been determined because of the inefficiency in
      genetic transformation. In this study, the function of a melanin biosynthetic
      gene was determined to examine its role in morphology and virulence. A polyketide
      synthase gene (termed as RnPKS1) in the R. necatrix genome is homologous to the
      1,8-dihydroxynaphthalene (DHN) melanin biosynthetic gene of Colletotrichum
      lagenarium. Melanin-deficient strains of R. necatrix were obtained by RNA
      interference-mediated knockdown of RnPKS1. The virulence of these strains was not
      significantly reduced compared with the parental melanin-producing strain.
      However, knockdown strains failed to develop pseudosclerotia and were degraded
      sooner in soil than the parental strain. Microscopic observations of albino
      conidiomata produced by knockdown strains revealed that melanization is involved
      in synnema integrity. These results suggest that melanin is not necessary for R.
      necatrix pathogenesis but is involved in survival through morphogenesis. This is
      the first report on the functional analysis of an endogenous target gene in R.
      necatrix. 

PMID- 24742837
TI  - Adenylate cyclase orthologues in two filamentous entomopathogens contribute
      differentially to growth, conidiation, pathogenicity, and multistress responses.
AB  - Adenylate cyclase (AC) is a core element of cAMP signalling network. Here we show
      functional diversity and differentiation of Beauveria bassiana AC (BbAC) and
      Metarhizium robertsii AC (MrAC). Severe growth defects occurred in DeltaBbAC and
      DeltaMrAC grown on nutrition-rich SDAY and several minimal media but were largely
      alleviated by adding cAMP to SDAY. Conidial yield increased greatly in DeltaBbAC
      but decreased in DeltaMrAC. During colony growth, DeltaBbAC was highly sensitive
      to oxidation, high osmolarity, cell wall perturbation, carbendazim fungicide,
      Mn(2+), Zn(2+), Fe(3+), and EDTA but more tolerant to Cu(2+) while DeltaMrAC
      showed higher osmotolerance, decreased sensitivity to Fe(3+), and null response
      to carbendazim or cell wall stress despite similar responses to oxidation and
      other metal ions. Conidial UV-B resistance decreased by 32% in DeltaBbAC and 22%
      in DeltaMrAC despite little change in their theromotolerance. Median lethal time
      (LT50) estimates of DeltaBbAC and DeltaMrAC against susceptible insects were 10.9
      and 1.4 d longer than those from wild-type strains respectively. All the
      phenotypic changes were restored to wild-type levels by each gene
      complementation. Taken together, BbAC and MrAC regulated differentially
      conidiation, pathogenicity, and multistress responses in B. bassiana and M.
      robertsii, thereby making different contributions to their biocontrol potential.

PMID- 24742838
TI  - The ethical implications of "more than one way to skin a cat": increasing use of
      radiation therapy to treat nonmelanoma skin cancers by dermatologists.

PMID- 24742839
TI  - Ductal hypoxia in acne: is it the missing link between comedogenesis and
      inflammation?

PMID- 24742840
TI  - Maintenance of certification in dermatology--what we know, what we don't.

PMID- 24742841
TI  - Comment on 'A double-blind, randomized, placebo-controlled trial of adalimumab in
      the treatment of cutaneous sarcoidosis'.

PMID- 24742842
TI  - A response to "Comment on 'A double-blind, randomized, placebo-controlled trial
      of adalimumab in the treatment of cutaneous sarcoidosis'".

PMID- 24742843
TI  - Robotic teledermatopathology from an African dermatology clinic.

PMID- 24742844
TI  - Expression of programmed death receptor ligand 1 in melanoma may indicate tumor
      progression and poor patient survival.

PMID- 24742845
TI  - JAAD Grand Rounds quiz. Adult with vesicles and bullae.

PMID- 24742846
TI  - JAAD Grand Rounds quiz. Necrotic plaques in a traveler.

PMID- 24742847
TI  - JAAD Grand Rounds quiz. Vacation dermatoses.

PMID- 24742848
TI  - The spectrum of oculocutaneous disease: Part I. Infectious, inflammatory, and
      genetic causes of oculocutaneous disease.
AB  - Many skin diseases are associated with ocular findings, emphasizing the need for
      dermatologists to be fully aware of their presence, and as a result, avoid
      overlooking conditions with potentially major ocular complications, including
      blindness. We review important oculocutaneous disease associations with
      recommendations for the management of the ocular complications and appropriate
      referral to our ophthalmology colleagues. Part I of this 2-part review focuses on
      the infectious, inflammatory, and genetic relationships. 

PMID- 24742849
TI  - The spectrum of oculocutaneous disease: Part II. Neoplastic and drug-related
      causes of oculocutaneous disease.
AB  - There are a multitude of diseases that commonly affect both the skin and the eye.
      Part II of this 2-part series reviews the oculocutaneous manifestations of
      neoplasms, both benign and malignant, and adverse drug reactions affecting the
      skin and the eye. Though rare, a number of neoplasms that primarily involve the
      skin, such as melanoma and basal cell carcinoma, can metastasize to the eye,
      leading to permanent damage if not properly treated. In addition, periocular
      neoplasms can irritate the conjunctiva and lid, reducing a patient's ability to
      see clearly. Neoplastic diseases, such as xeroderma pigmentosum, Sturge-Weber
      syndrome, and multiple myeloma, can also lead to permanent changes in the eye if
      not discovered and managed promptly. Furthermore, there are a multitude of drugs,
      including those commonly used by dermatologists, which can result in permanent
      damage to the eye. With proper knowledge of the ocular manifestations and
      treatment recommendations described in this 2-part series, dermatologists with
      the assistance of their ophthalmology colleagues can help avoid the
      complications, including permanent blindness, associated with infectious,
      inflammatory, genetic, neoplastic, and drug-related conditions. 

PMID- 24742850
TI  - Adhesive tape technique to enhance potassium hydroxide diagnosis of occult fungal
      infections.

PMID- 24742851
TI  - Treatment of molluscum contagiosum with ingenol mebutate.

PMID- 24742852
TI  - A unique protective bandage for preauricular surgery.

PMID- 24742853
TI  - Brimonidine effective but may lead to significant rebound erythema.

PMID- 24742854
TI  - Trigeminal trophic syndrome secondary to recurrent meningioma.

PMID- 24742855
TI  - Striking leflunomide efficacy against refractory cutaneous sarcoidosis.

PMID- 24742856
TI  - Localized bullous fixed drug eruption following yellow fever vaccine.

PMID- 24742859
TI  - Uncovering a hidden basal cell carcinoma.

PMID- 24742860
TI  - An electromagnetic microvalve for pneumatic control of microfluidic systems.
AB  - An electromagnetic microvalve for pneumatic control of microfluidic devices has
      been designed, fabricated, and tested. The microvalve is composed of two parts: a
      miniature electromagnetic actuator and a valve body. The electromagnetic actuator
      consists mainly of a thin polydimethylsiloxane (PDMS)-based elastomer, which acts
      as the valve diaphragm. The diaphragm, used as a solid hydraulic medium, converts
      the large contact area of a valve core into a small contact area of valve head
      while maintaining a large stroking force. This microvalve remains closed because
      of a compressed mechanical spring force generated by the actuator. On the other
      hand, when a voltage is applied, the valve core moves up, relaxing the thin PDMS
      membrane, opening the microvalve. The fast open response (~17 ms) of the valve
      was achieved with a leak rate as low as 0.026 sccm at 200 KPa (N2) pressure. We
      tested the pertinent dynamic parameters such as flow rate in on/off mode, flow
      rate of duty cycles, and actuated frequencies in pulse width modulation (PWM)
      mode. Our method provides a simple, cheap, and small microvalve that avoids the
      bulky and expensive external pressure control solenoid manifold. This allows it
      to be easily integrated into portable and disposable devices. 

PMID- 24742861
TI  - Dyspraxia, motor function and visual-motor integration in autism.
AB  - This project assessed dyspraxia in high-functioning school aged children with
      autism with a focus on Ideational Praxis. We examined the association of specific
      underlying motor function including eye movement with ideational dyspraxia
      (sequences of skilled movements) as well as the possible role of visual-motor
      integration in dyspraxia. We found that compared to IQ-, sex- and age-matched
      typically developing children, the children with autism performed significantly
      worse on: Ideational and Buccofacial praxis; a broad range of motor tests,
      including measures of simple motor skill, timing and accuracy of saccadic eye
      movements and motor coordination; and tests of visual-motor integration.
      Impairments in individual children with autism were heterogeneous in nature,
      although when we examined the praxis data as a function of a qualitative measure
      representing motor timing, we found that children with poor motor timing
      performed worse on all praxis categories and had slower and less accurate eye
      movements while those with regular timing performed as well as typical children
      on those same tasks. Our data provide evidence that both motor function and
      visual-motor integration contribute to dyspraxia. We suggest that dyspraxia in
      autism involves cerebellar mechanisms of movement control and the integration of
      these mechanisms with cortical networks implicated in praxis. 

PMID- 24742862
TI  - Dorsal hippocampus inactivation impairs spontaneous recovery of Pavlovian
      magazine approach responding in rats.
AB  - Destruction or inactivation of the dorsal hippocampus (DH) has been shown to
      eliminate the renewal of extinguished fear [1-4]. However, it has recently been
      reported that the contextual control of responding to extinguished appetitive
      stimuli is not disrupted when the DH is destroyed or inactivated prior to tests
      for renewal of Pavlovian conditioned magazine approach [5]. In the present study
      we extend the analysis of DH control of appetitive extinction learning to the
      spontaneous recovery of Pavlovian conditioned magazine approach responding.
      Subjects were trained to associate two separate stimuli with the delivery of food
      and had muscimol or vehicle infused into the DH prior to a single test-session
      for spontaneous recovery occurring immediately following extinction of one of
      these stimuli, but one week following extinction of the other. While vehicle
      treated subjects showed more recovery to the distally extinguished stimulus than
      the proximal one, muscimol treated subjects failed to show spontaneous recovery
      to either stimulus. This result suggests that, while the DH is not involved in
      the control of extinction by physical contexts [5], it may be involved when time
      is the gating factor controlling recovery of extinguished responding. 

PMID- 24742863
TI  - To like or not to like: neural substrates of subjective flavor preferences.
AB  - Flavor preferences vary; what one enjoys may be disgusting to another. Previous
      research has indicated several brain regions associated with flavor preferences.
      However, by using different stimuli or different internal states to obtain
      differences in liking, results of these studies may be confounded. Therefore, we
      used one target stimulus (grapefruit juice) and fMRI to compare brain activation
      patterns between participants that either liked (n=16) or disliked (n=18) this
      stimulus. Our first aim was to investigate whether differential neural activation
      exists that accounts for the difference in subjective flavor preference for the
      target stimulus. Secondly, multivariate analysis was used to investigate whether
      differences in subjective liking for the target revealed similar activation
      patterns as differences in general liking for a sweet and bitter solution. A
      direct comparison of likers and dislikers of the target stimulus revealed only
      small differences in activations in orbitofrontal cortex (OFC) and dorsal
      anterior cingulate cortex (dACC). However, when using multivariate analysis, a
      broader activation pattern (including OFC, dACC, pregenual anterior cingulate,
      anterior insula and ventral striatum) was identified that discriminated likers
      from dislikers with an 88% success rate. Interestingly though, little overlap was
      found between this pattern and the pattern that discriminates liking for the
      sweet and bitter solutions and lesser voxels contributed to the former compared
      with the latter. These differences between patterns discerning innate versus
      learned preferences may suggest that different mechanisms are at work and
      highlight the importance of elucidating the neural processes of how subjective
      preferences are learned and acquired.

PMID- 24742864
TI  - Psychosocial and contextual determinants of alcohol and drug use disorders in the
      National Latino and Asian American Study.
AB  - BACKGROUND: In the U.S., Latino and Asian American immigrants and ethnic
      minorities may be at increased risk for alcohol and drug use disorders
      (AUDs/DUDs). The role of psychosocial and contextual characteristics as potential
      factors underlying this increased risk is unresolved. METHODS: Participants
      include 4649 adults from the National Latino and Asian American Study. Logistic
      regression was used to determine the relationship between acculturation,
      acculturative stress, neighborhood characteristics, family characteristics, and
      discrimination and AUDs/DUDs. Models were stratified by age of immigration and
      ethnicity and controlled for demographic and mental health characteristics.
      RESULTS: Overall, 9.6% of Latino and 4.1% of Asian participants met criteria for
      lifetime AUDs/DUDs. Acculturation, family conflict, and discrimination were
      positively associated with AUDs/DUDs (odds ratios [ORs] and 95% confidence
      intervals [95%CIs]: 1.80[1.54-2.09], 1.24[1.12-1.36], and 1.54[1.38-1.73]), while
      neighborhood safety and family cohesion were protective for AUDs/DUDs
      (ORs[95%CIs]: 0.75[0.66-0.85] and 0.79[0.69-0.90]). Acculturative stress and
      neighborhood cohesion were not related to AUDs/DUDs. The relationships between
      family conflict and family cohesion with AUDs/DUDs were attenuated after
      accounting for other psychosocial and contextual factors. These relationships
      were generally consistent across ethnic and age of immigration subgroups.
      CONCLUSIONS: Factors such as acculturation, discrimination, and neighborhood
      safety, are robustly and largely universally related to AUDs/DUDs among first and
      later generation Latino and Asian immigrants. Further research is required to
      understand how and why these factors relate to risk of substance misuse, and to
      identify ways to apply these factors in prevention and intervention efforts.

PMID- 24742865
TI  - Antiangiogenic therapy using sunitinib combined with rapamycin retards tumor
      growth but promotes metastasis.
AB  - BACKGROUND: This study investigated the synergistic effect of sunitinib and
      rapamycin on tumor growth and metastasis in murine breast cancer model. METHODS:
      The synergistic antitumor effect of sunitinib and rapamycin on tumor growth and
      metastasis was investigated. Myeloid-derived suppressor cells (MDSCs) in spleens
      and lungs were assessed. Tumor hypoxia, vessel density and micrometastasis were
      evaluated. Versican, indoleamine 2,3-dioxygenase (IDO), arginase 1, interleukin-6
      (IL-6), IL-10, and transforming growth factor beta (TGF-beta) in the lungs and
      tumors were examined. IL-6 and TGF-beta in the blood were evaluated. RESULTS:
      Synergism between sunitinib and rapamycin on tumor growth was observed. Sunitinib
      plus rapamycin reduced splenomegaly, MDSCs in spleens and lungs, and microvessel
      density in tumor microenvironment, while exacerbated hypoxia and promoted cancer
      lung metastasis. Sunitinib plus rapamycin markedly induced versican, IDO,
      arginase 1, IL-6, and TGF-beta expression in the lungs, whereas it reduced IDO
      and IL-10 expression in the primary tumor tissues. IL-6 levels in the circulation
      were increased after rapamycin and combination therapies. CONCLUSIONS: The
      combination of sunitinib plus rapamycin reduced the tumor growth but promoted
      tumor metastasis. This study warrants that further mTOR inhibition treatment
      should be closely watched in clinical setting, especially combined with
      antiangiogenic therapy.

PMID- 24742868
TI  - Violence Against Women. Self-defense against sexual assault. Guest editors'
      introduction.

PMID- 24742867
TI  - TERT promoter mutations in renal cell carcinomas and upper tract urothelial
      carcinomas.
AB  - TERT promoter mutations are identified in many malignancies including bladder
      cancer (BC) and upper tract urothelial carcinoma (UTUC). In contrast, no
      mutations were found in renal cell carcinoma (RCC) as reported in a recent study.
      Because the mutant TERT promoter in urine DNA was recently tested as a marker for
      BC, it is important to ascertain whether these mutations are truly absent in
      RCCs. Here we determined TERT promoter mutations in 109 patients with RCC and 14
      patients with UTUC. The mutations were found in 9/96 (9.3%) clear cell RCC
      (ccRCC) tumors and 1/8 (13%) chromophobe RCC tumors. Among ccRCC patients, the
      mutation was correlated with the advanced stages and metastasis, and higher TERT
      expression. Among UTUCs, the mutation was detected in tumors from 3/5 (60%)
      patients with renal pelvic cancer and 1/9 (11%) patients with ureter cancer. The
      mutation was also detected in 1 of 4 urine samples from patients with mutation+
      UTUC. Collectively, TERT promoter mutations do occur in RCCs and are associated
      with aggressive disease. The mutation is more frequent in renal pelvic cancer.
      Thus, the mutant TERT promoter found in urine may come from not only BC, but also
      RCC or UTUC. 

PMID- 24742869
TI  - Self-defense training as clinical intervention for survivors of trauma.
AB  - A well-designed self-defense curriculum, congruent with psychophysiologically
      informed trauma research and treatment, and integrated with input from
      therapists, can serve as an important adjunctive treatment. We provide a detailed
      description of such a program modified to be an experiential, psychoeducational
      intervention for female survivors of trauma. Recent research on the role of
      blocked motor responses in the development of pathology post-trauma is explored
      as a potential explanatory mechanism for the therapeutic benefits of self-defense
      training. Through specific examples and descriptions of teaching methods, we
      examine how this intervention compliments and augments traditional
      psychotherapeutic treatment of trauma sequelae. 

PMID- 24742870
TI  - Self-defense or undermining the self? Exploring the possibilities and limitations
      of a novel anti-rape technology.
AB  - Despite decades of feminist-inspired law reforms, rape remains highly prevalent.
      While many continue to fight for broad cultural and institutional changes, some
      argue that more immediate interventions are required. Self-defense techniques
      represent a key strategy of resistance to rape, and empirical evidence suggests
      that women's active resistance may hold a number of positive benefits. In this
      essay, we compare the aims and objectives of a novel anti-rape technology, known
      as the Rape-aXe, with traditional self-defense techniques, focusing upon the
      potential for both to resist individual acts of sexual aggression and, more
      broadly, end gendered sexual violence. 

PMID- 24742871
TI  - The welfare of Australian livestock transported by sea.

PMID- 24742872
TI  - Radiographic scoring for intervertebral disc calcification in the Dachshund.
AB  - Intervertebral disc disease is a common, painful and debilitating neurological
      condition of dogs, causing substantial morbidity and mortality. The Dachshund is
      particularly susceptible to this disorder. The goal of this article is not to
      duplicate previously published reviews on canine intervertebral disc degeneration
      and degenerative diseases. Rather, the aims are threefold: (1) to reflect on
      selected clinical and pathophysiological aspects of intervertebral disc
      degeneration and disc disease that are pertinent to the Dachshund breed; (2) to
      review a radiographic spinal scoring scheme developed to reduce the prevalence of
      intervertebral disc disease in Dachshunds; and (3) to suggest further areas of
      research to improve upon the currently established scoring scheme in an attempt
      to address this breed's greatest health problem.

PMID- 24742873
TI  - Contribution of VDR polymorphisms to type 1 diabetes susceptibility: Systematic
      review of case-control studies and meta-analysis.
AB  - Vitamin D receptor (VDR) polymorphisms have been inconsistently investigated in
      type 1 diabetes (T1D). However, the results are inconsistent and inconclusive.
      The current study aimed to investigate the role of TaqI, BsmI, ApaI and FokI VDR
      polymorphisms in T1D disease. Following the Preferred Reporting Items for
      Systematic Reviews and Meta-analyses (PRISMA) guidelines, a systematic search and
      meta-analysis of the literature, since 1998 until december 2013, was conducted.
      Subgroup analyses were performed to detect potential sources of heterogeneity
      from selected study characteristics. Meta-analyses yielded a non-significant
      association of TaqI polymorphism with T1D [OR=1.014 (0.783-1.312); P=0.918] in
      the recessive model. The BsmI polymorphism was not associated with T1D [OR=1.44
      (0.944-1.386); P=0.171] in the dominant model. Also, ApaI polymorphism was not
      associated with T1D risk [OR=0.996 (0.859-1.155); P=0.960] in the homozygous
      model. The FokI polymorphism was not associated with T1D risk [OR=0.968 (0.743
      1.263); P=0.813] in dominant model. Stratification according to study
      characteristics showed that publication year, age, gender, estimated vitamin D
      levels and latitude moderated significantly association between VDR polymorphisms
      and T1D disease. Meta-analysis on haplotypes revealed that BAT might be a
      significant risk factor for T1D [OR=1.331 (0.957-1.850; P=0.089]. However, the
      bAT was found to be a significant protective factor [OR=0.639 (0.460-0.887);
      P=0.007]. As conclusion, individual VDR polymorphisms seemed not to be associated
      with T1D risk. However, haplotypes contributed significantly to disease
      susceptibility. Study characteristics moderated the association between VDR
      polymorphisms and T1D. These results suggested that, in T1D pathogenesis, VDR
      polymorphisms interact with each other and with environmental factors. 

PMID- 24742874
TI  - Relationship between objectively measured physical activity and vascular
      structure and function in adults.
AB  - OBJECTIVES: To analyze the relationship between regular physical activity, as
      assessed by accelerometer and 7-day physical activity recall (PAR) with vascular
      structure and function based on carotid intima-media thickness, pulse wave
      velocity, central and peripheral augmentation index and the ambulatory arterial
      stiffness index in adults. METHODS: This study analyzed 263 subjects who were
      included in the EVIDENT study (mean age 55.85 +/- 12.21 years; 59.30% female).
      Physical activity was assessed during 7 days using the Actigraph GT3X
      accelerometer (counts/minute) and 7-day PAR (metabolic equivalents
      (METs)/hour/week). Carotid ultrasound was used to measure carotid intima media
      thickness (IMT). The SphygmoCor System was used to measure pulse wave velocity
      (PWV), and central and peripheral augmentation index (CAIx and PAIx). The B-pro
      device was used to measure ambulatory arterial stiffness index (AASI). RESULTS:
      Median counts/minute was 244.37 and mean METs/hour/week was 11.49. Physical
      activity showed an inverse correlation with PAIx (r = -0.179; p < 0.01) and
      vigorous activity day time with IMT (r = -0.174), CAIx (r = -0.217) and PAIx (r =
      -0.324) (p < 0.01, all). Sedentary activity day time was correlated positively
      with CAIx (r = 0.103; p < 0.05). In multiple regression analysis, after adjusting
      for confounding factors, the inverse association of CAIx with counts/minute and
      the time spent in moderate and vigorous activity were maintained as well as the
      positive association with sedentary activity day time (p < 0.05). CONCLUSION:
      Physical activity, assessed by counts/minute, and the amount of time spent in
      moderate, vigorous/very vigorous physical activity, showed an inverse association
      with CAIx. Likewise, the time spent in sedentary activity was positively
      associated with the CAIx. TRIAL REGISTRATION: Clinical Trials.gov Identifier:
      NCT01083082.

PMID- 24742876
TI  - "We're all thrown in the same boat ... ": A qualitative analysis of peer support
      in dementia care.
AB  - Peer support is well established in fields such as the disability movement and
      mental health and is increasingly recognised as one way of enabling support by
      and for people with a diagnosis of dementia and their immediate carers. It was
      central to the implementation of the National Dementia Strategy (NDS) for
      England, when 40 demonstration sites were established. This mixed-methods study
      included in-depth qualitative interviews with people living with dementia (n =
      101) and staff/stakeholders (n = 82) at 8 of the 40 sites. Data analysis was a
      five-stage process: coding framework developed (using 25 transcripts); further
      development of the framework (using a further 70 transcripts); development of
      emerging themes; modelling of themes and verification of models based on the
      entire data set. Peer support had positive emotional and social impact that was
      rooted in identification with others, a commonality of experience and reciprocity
      of support. There was also a contrast between the quality of peer support and
      support from professionals. This emphasises the significance of lived experience
      and promoting a strength-based approach to interpersonal support that is enabling
      and challenges a deficit approach to understanding dementia. 

PMID- 24742875
TI  - Pro-inflammatory cytokine levels are raised in female schizophrenia patients
      treated with clozapine.
AB  - BACKGROUND: We have previously shown that the neurotrophic factor, S100B, is
      raised in serum samples of female patients with schizophrenia, but not male
      patients, compared to controls, and this may be associated with raised BMI. Here
      we analysed the levels of additional proinflammatory cytokines in patients with
      schizophrenia to further investigate these gender differences. METHODS: The
      levels of six cytokines (IL1beta, IL6, IL8, IL17, IL23, TNFalpha) were measured
      in serum samples obtained from patients with schizophrenia, treated with
      clozapine (n=91) and compared with healthy controls (n=50). Individual cytokine
      levels were measured using dot-immunoblotting methods and a 'cytokine signature'
      was also generated by summing all 6 cytokines. Treatment time, patient age,
      gender, illness severity and metabolic parameters were also measured. RESULTS:
      The levels of proinflammatory cytokines and BMI were significantly raised in
      female, but not male, patients treated with clozapine compared to healthy
      controls. Compared to individual cytokines, the 'cytokine signature' analysis
      showed less scatter of data although this 'cytokine signature' method did not
      improve separation of individual patients and controls. CONCLUSIONS: This study
      supports previous findings that raised BMI, which is likely associated with
      increased number of adipocytes, may contribute to increased cytokine serum
      concentrations in females.

PMID- 24742877
TI  - Crucial dimensions constituting dignity experience in persons living with
      dementia.
AB  - Dignity is seen as an essential need, fundamental right, and inherent quality of
      each human being. There is however, a need for increased knowledge on crucial
      dimensions constituting dignity experience in persons living with dementia. This
      study explored personal dimensions of life which persons with dementia perceived
      crucial for experiencing dignity in their daily lives. Based on the findings of
      eight empirical sub-dimensions, three main dimensions crucial for constituting
      dignity experience, were identified through hermeneutical interpretation: A
      historical dignity-dimension, acknowledging one's own life-projects and life
      history; an intrapersonal dignity-dimension, recognizing one's own human worth,
      and living according to internal values; and an interpersonal dignity-dimension,
      experiencing being part of a caring and confirming communion. Knowledge of
      dignity preservation should be a crucial foundation for future dementia care. 

PMID- 24742878
TI  - Nutritional contributions of insects to primate diets: implications for primate
      evolution.
AB  - Insects and other invertebrates form a portion of many living and extinct primate
      diets. We review the nutritional profiles of insects in comparison with other
      dietary items, and discuss insect nutrients in relation to the nutritional needs
      of living primates. We find that insects are incorporated into some primate diets
      as staple foods whereby they are the majority of food intake. They can also be
      incorporated as complements to other foods in the diet, providing protein in a
      diet otherwise dominated by gums and/or fruits, or be incorporated as supplements
      to likely provide an essential nutrient that is not available in the typical
      diet. During times when they are very abundant, such as in insect outbreaks,
      insects can serve as replacements to the usual foods eaten by primates.
      Nutritionally, insects are high in protein and fat compared with typical dietary
      items like fruit and vegetation. However, insects are small in size and for
      larger primates (>1 kg) it is usually nutritionally profitable only to consume
      insects when they are available in large quantities. In small quantities, they
      may serve to provide important vitamins and fatty acids typically unavailable in
      primate diets. In a brief analysis, we found that soft-bodied insects are higher
      in fat though similar in chitin and protein than hard-bodied insects. In the
      fossil record, primates can be defined as soft- or hard-bodied insect feeders
      based on dental morphology. The differences in the nutritional composition of
      insects may have implications for understanding early primate evolution and
      ecology.

PMID- 24742879
TI  - Asymmetry of the midfacial skeleton of eastern lowland gorillas (Gorilla beringei
      graueri) and potential association with frontal lobe asymmetries.

PMID- 24742880
TI  - Two-dimensional proteomic analysis of gonads of air-breathing catfish, Clarias
      batrachus after the exposure of endosulfan and malathion.
AB  - Endocrine disrupting chemicals have raised public concern, since their effects
      have been found to interfere with the physiological systems of various organisms,
      especially during critical stage of development and reproduction. Endosulfan and
      malathion, pesticides widely used for agricultural purposes, have been known to
      disrupt physiological functions in aquatic organisms. The current work analyzes
      the effects of endosulfan (2.5 parts per billion [ppb]) and malathion (10 ppb) on
      the reproductive physiology of catfish (Clarias batrachus) by evaluating protein
      expression profiles after 21 days of exposure. The proteomic profile of testis
      and ovary after exposure to endosulfan showed downregulation of proteins such as
      ubiquitin and Esco2, and upregulation in melanocortin-receptor-2 respectively.
      Malathion exposed ovary showed upregulated prolactin levels. Identification of
      proteins differentially expressed in gonads due to the exposure to these
      pesticides may serve as crucial indications to denote their disruptive effects at
      the level of proteins.

PMID- 24742881
TI  - 'She can't come here!' Ethics and the case of birth centre admission policy in
      the UK.
AB  - Using ethnographic data lifted from an investigation into midwifery talk and
      practice in the South of England, this paper sets out to interrogate the ethics
      underpinning current admission policy for Free Standing (midwifery led) Birth
      Centres in the UK. The aim of this interrogation is to contest the grounds upon
      which birth centres admissions are managed, particularly the over-reliance on
      abstract calculations of risk--far removed from the material lived experience of
      the mother wishing to access these birth centre services.

PMID- 24742882
TI  - The role of NHS gatekeeping in delayed diagnosis.

PMID- 24742883
TI  - US citizens' use of healthcare services rises.

PMID- 24742884
TI  - Disagreeing with NICE's evaluation of evidence is not grounds for a CCG to deny
      recommended treatment, judge rules.

PMID- 24742885
TI  - Psychiatrist who broke his wife's ankle is suspended for 12 months.

PMID- 24742887
TI  - Cardiac involvement in myotonic dystrophy: a nationwide cohort study.
AB  - AIMS: To quantify the association between myotonic dystrophy (DM) and cardiac
      disease in a nationwide cohort. METHODS AND RESULTS: We identified a nationwide
      cohort of 1146 DM patients (period 1977-2011) using the National Patient Registry
      (NPR) and a subcohort of 485 patients who had undergone genetic testing for DM1.
      Information on incident cardiac diseases was obtained from the NPR. We estimated
      standardized incidence ratios (SIRs) of cardiac disease compared with the
      background population, overall and according to selected diagnostic subgroups
      (cardiomyopathy, heart failure, conduction disorders, arrhythmias, and device
      implantation). In the DM cohort, SIR for any cardiac disease was 3.42 [95%
      confidence interval (CI) 3.01-3.86]; for a cardiac disease belonging to the
      selected subgroups 6.91 (95% CI: 5.93-8.01) and for other cardiac disease 2.59
      (95% CI: 2.03-3.25). For a cardiac disease belonging to the selected subgroups,
      the risk was particularly high in the first year after DM diagnosis [SIR 15.4
      (95% CI: 10.9-21.3)] but remained significantly elevated in subsequent years [SIR
      6.07 (95% CI: 5.11-7.16]). The risk was higher in young cohort members [e.g. 20
      39 years: SIR 18.1 (95% CI: 12.3-25.8)] compared with older [e.g. 60-79 years:
      SIR 3.99 (95% CI: 2.98-5.23)] but remained significantly increased in all age
      categories. Results were similar in separate analyses of the genetically
      confirmed DM1 patients. CONCLUSION: Myotonic dystrophy is strongly associated
      with cardiac disease. The risk is pronounced in the young and remains elevated
      throughout life, stressing the importance of lifelong cardiac follow-up from time
      of DM diagnosis.

PMID- 24742886
TI  - Association of circulating endothelial microparticles with cardiometabolic risk
      factors in the Framingham Heart Study.
AB  - OBJECTIVE: To examine the relation of endothelial microparticles (EMPs) with
      cardiometabolic risk in the community. BACKGROUND: Circulating EMPs are small
      membrane vesicles released after endothelial cell injury. Endothelial
      microparticles are reportedly increased among individuals with a high burden of
      cardiovascular risk factors. However, prior investigations have been limited to
      small, highly selected samples. METHODS: We studied 844 individuals without a
      history of cardiovascular disease in the Framingham Offspring cohort (mean age 66
      +/- 9 years, 57% women). We used standardized flow cytometry methods to identify
      and quantify circulating CD144+ and CD31+/CD41- EMPs. We then used multivariable
      regression analyses to investigate the relations of EMP phenotypes with
      cardiovascular and metabolic risk factors. RESULTS: In multivariable analyses,
      the following cardiovascular risk factors were associated with one or more of the
      circulating EMP populations: hypertension (P = 0.025 for CD144+,), elevated
      triglycerides (P = 0.002 for CD144+, P < 0.0001 for CD31+/CD41-), and metabolic
      syndrome (P < 0.0001 for CD144+,). Overall, each tertile increase in the
      Framingham risk score corresponded to a 9% increase in log-CD31+/CD41- EMPs (P =
      0.022). Furthermore, the presence of hypertriglyceridaemic waist status was
      associated with 38% higher levels of CD144+ EMPs (P < 0.0001) and 46% higher
      levels of CD31+/CD41- EMPs (P < 0.0001). CONCLUSION: In a large community-based
      sample, circulating EMP levels were associated with the presence of
      cardiometabolic risk factors, particularly dyslipidaemia. These data underscore
      the potential influence of high-risk metabolic profiles on endothelial integrity.

PMID- 24742888
TI  - The organization, function, and outcomes of ST-elevation myocardial infarction
      networks worldwide: current state, unmet needs and future directions.
AB  - The organization of networks in order to better coordinate and to faster offer
      reperfusion strategies for acute ST-elevation myocardial infarction (STEMI) is an
      important recommendation of recent versions of international guidelines. This
      article focusses on similarities and dissimilarities of world-wide networks,
      highlights essential network components, offers insights into still unmet needs
      and discusses potential measures to further improve quality of STEMI treatment. 

PMID- 24742889
TI  - Gene expression profiling: time to file diagnostic uncertainty in inflammatory
      heart diseases?

PMID- 24742890
TI  - 3D imaging of device leads: "taking the lead with 3D".

PMID- 24742891
TI  - A microvascular-myocardial diastolic dysfunctional state and risk for mental
      stress ischemia: a revised concept of ischemia during daily life.

PMID- 24742892
TI  - The role of imaging in aortic dissection and related syndromes.
AB  - Aortic aneurysm and acute aortic syndrome are not uncommon conditions. Management
      of acute aortic dissection and related syndromes requires a multidisciplinary
      approach with input from the patient, clinician, imager, surgeon, and
      anesthesiologist. This requires an integrated evaluation of pathophysiology,
      anatomy, and severity to enable appropriate therapy. This review includes
      discussion of essential anatomy of the aortic valve and the aorta that determines
      the candidacy for surgical repair. It also includes discussion of various imaging
      modalities, particularly echocardiography, cardiac computed tomography, and
      cardiac magnetic resonance angiography. The relative benefits and demerits of
      each of these techniques are reviewed. This paper is intended to help guide
      management decisions for patients with acute aortic dissection and related
      syndromes. 

PMID- 24742893
TI  - LV outflow tract area in discrete subaortic stenosis and hypertrophic obstructive
      cardiomyopathy: a real-time 3-dimensional transesophageal echocardiography study.

PMID- 24742894
TI  - Safety and feasibility of contrast echocardiography for LVAD evaluation.

PMID- 24742896
TI  - In the footsteps of Virchow.

PMID- 24742895
TI  - Ex vivo cryoimaging for plaque characterization.

PMID- 24742897
TI  - Reply: in the footsteps of Virchow.

PMID- 24742898
TI  - Mentees, mentors, and the mentorship....

PMID- 24742899
TI  - Cardiovascular imaging in the pediatric population.

PMID- 24742901
TI  - The imbalance of sodium and potassium intake: implications for dietetic practice.

PMID- 24742900
TI  - Advanced gynecologic malignancies treated with a combination of the VEGF
      inhibitor bevacizumab and the mTOR inhibitor temsirolimus.
AB  - BACKGROUND: Bevacizumab and temsirolimus are active agents in gynecologic tumors.
      Temsirolimus attenuates upregulation of HIF-1alpha levels, a resistance mechanism
      for antiangiogenics, and targets the PI3-kinase/AKT/mTOR axis, commonly aberrant
      in these tumors. PATIENTS AND METHODS: We analyzed safety and responses in 41
      patients with gynecologic cancers treated as part of a Phase I study of
      bevacizumab and temsirolimus. RESULTS: Median age of the 41 women was 60 years
      (range, 33-80 years); median number of prior systemic therapies was 4 (1-11).
      Grade 3 or 4 treatment-related toxicities included: thrombocytopenia (10%),
      mucositis (2%), hypertension (2%), hypercholesterolemia (2%), fatigue (7%),
      elevated aspartate aminotransferase (2%), and neutropenia (2%). Twenty-nine
      patients (71%) experienced no treatment-related toxicity greater than grade 2.
      Full FDA-approved doses of both drugs (bevacizumab 15mg/kg IV Q3weeks and
      temsirolimus 25mg IV weekly) were administered without dose-limiting toxicity.
      Eight patients (20%) achieved stable disease (SD) > 6 months and 7 patients
      (17%), a partial response (PR) [total = 15/41 patients (37%)]. Eight of 13
      patients (62%) with high-grade serous histology (ovarian or primary peritoneal)
      achieved SD > 6 months/PR. CONCLUSION: Bevacizumab and temsirolimus was well
      tolerated. Thirty-seven percent of heavily-pretreated patients achieved SD > 6
      months/PR, suggesting that this combination warrants further study.

PMID- 24742902
TI  - Changes in the synganglion of Rhipicephalus sanguineus (Latreille, 1806) (Acari:
      Ixodidae) female ticks exposed to permethrin: an ultrastructural overview.
AB  - This study performed the ultra-structural analysis of the changes caused by
      permethrin in the synganglion of semi-engorged Rhipicephalus sanguineus females,
      aiming to understand the toxic action of this substance at cellular level. The
      results showed that the neural lamella had its structure changed, allowing the
      influx of the toxic agent into the nervous tissue. The glial cells of the
      perineurium, as well as the neural cells of the cortex showed great changes, such
      as: irregular nuclei with chromatin margination, cytoplasmic vacuolation and
      degenerating mitochondria. These changes showed that the permethrin would be able
      to induce the degeneration of the synganglion through an atypical death process,
      involving apoptosis and autophagy. In addition, a dilated rough endoplasmic
      reticulum was observed in the neural cells, suggesting an intense synthesis of
      the hydrolytic enzymes that would be used in the processes of degradation of the
      damaged cellular structures (formation of lysosomes). The subperineurium and the
      neuropile also showed changes in their structures. Thus, it is suggested that
      permethrin is a dose-dependent compound able to impair the metabolism of the
      organism as a whole, once all the other organs and body structures are directly
      dependent of the neural control. The information obtained in this study can be
      used in the improvement of the control methods which use permethrin as active
      substance, helping in the creation of a really efficient acaricide product to
      fight this important urban plague. 

PMID- 24742904
TI  - Chewing lice (Phthiraptera) from Calidris fuscicollis (Aves: Scolopacidae) in
      Southern Brazil.
AB  - During April and September from 2010 to 2012, 80 birds of the species Calidris
      fuscicollis (white-rumped sandpiper) were collected for parasitological studies
      in the southern coast of Rio Grande do Sul, under ICMBIO license No. 26234-1. For
      ectoparasite collection, the birds were first submerged in water with detergent.
      The parasites found were fixed in 70% alcohol, cleared in 10% potassium hydroxide
      and mounted in Canada balsam. Of 80 birds examined, 79% were parasitized.
      Actornithophilus umbrinus (47.5%), Actornithophilus lacustris (37.5%),
      Actornithophilus spp. (13.75%), Carduiceps zonarius (26.25%), Lunaceps incoenis
      (27.5%), and Lunaceps spp. (16.25%) were the species found with their respective
      prevalence. We record for the first time parasitism by chewing lice in Calidris
      fuscicollis. 

PMID- 24742903
TI  - Natural breeding sites of phlebotomine sand flies (Diptera: Psychodidae) on
      Marambaia Island, Rio de Janeiro State, Brazil.
AB  - Immature phlebotomine sand flies develop in soils with essential and ideal
      characteristics for their life cycle, such as organic matter, humidity,
      temperature and low levels of light. Information regarding the potential breeding
      places of these dipterans is fundamental to understand the epidemiology and
      ecology of leishmaniasis, in addition to its importance to control them. In the
      present study, we aimed to find natural breeding sites of sand flies on Marambaia
      Island with the aid of emergence traps and direct search of immature forms using
      the flotation technique with saturated sugar solution in organic substrates of
      the region. Both methods were effective, with a total of 42 specimens of six
      different species - including some species that participate in the transmission
      cycle of American Tegumentary Leishmaniasis - collected by the emergence traps,
      and five immature forms obtained by floatation technique. However, further
      studies are still necessary, mainly with respect to the ecology and biology of
      immature sandfly stages, so that control measures focused on breeding sites can
      produce positive sustainable results in natural environments. 

PMID- 24742905
TI  - Ultrastructure of immature stages of Lucilia cuprina (Diptera: Calliphoridae)
      using scanning electron microscopy.
AB  - The blowfly Lucilia cuprina is distributed worldwide and is a mechanical vector
      of pathogens. It can cause myiasis in humans and is strongly related to forensic
      entomology, as it is frequently found on human and animal corpses. However, most
      of the L. cuprina found on corpses are the immature stages of this fly. Correct
      identification is very important for forensic entomology but at present only the
      identification keys of adult L. cuprina are available. Thus, the aim of this
      paper was to describe and analyze the morphological characteristics of all larval
      instars and the puparia of L. cuprina using scanning electron microscopy (SEM). 

PMID- 24742906
TI  - Anti-Trypanosoma cruzi activity of 10 medicinal plants used in northeast Mexico.
AB  - The aim of this study was to screen the trypanocidal activity of plants used in
      traditional Mexican medicine for the treatment of various diseases related to
      parasitic infections. Cultured Trypanosoma cruzi epimastigotes were incubated for
      96h with different concentrations of methanolic extracts obtained from Artemisia
      mexicana, Castela texana, Cymbopogon citratus, Eryngium heterophyllum,
      Haematoxylum brasiletto, Lippia graveolens, Marrubium vulgare, Persea americana,
      Ruta chalepensis and Schinus molle. The inhibitory concentration (IC50) was
      determined for each extract via a colorimetric method. Among the evaluated
      species, the methanolic extracts of E. heterophyllum, H. brasiletto, M. vulgare
      and S. molle exhibited the highest trypanocidal activity, showing percentages of
      growth inhibition between 88 and 100% at a concentration of 150MUg/ml. These
      medicinal plants may represent a valuable source of new bioactive compounds for
      the therapeutic treatment of trypanosomiasis. 

PMID- 24742907
TI  - A community-based study to examine the epidemiology of human cystic
      echinococcosis in Rio Negro Province, Argentina.
AB  - Although cystic echinococcosis (CE) is an important public health problem in Rio
      Negro Province, current epidemiological data for CE, in this region of Argentina,
      are not available. Therefore, a community-based study, which incorporated
      diagnostic imaging and a questionnaire, was conducted in Ingeniero Jacobacci, a
      small town in southern Rio Negro Province. This study sought to assess the
      prevalence of human CE, in the study population, and to evaluate epidemiologic
      factors associated with CE transmission within the study area. Of the 560
      individuals who volunteered to participate in the study, 189 (34%) were children
      and 371 (66%) were adults. All study participants were screened for CE using
      abdominal ultrasound scanning, with CE-positive or suspect individuals also
      receiving thoracic radiographs. The overall prevalence of CE was 7.1% (40/560),
      with 1.6% (3/189) of children, and 10% (37/371) of adults diagnosed as CE
      positive. Although 92.5% (37/40) of the CE-positive individuals had only hepatic
      lesions, two participants had both hepatic and pulmonary lesions, and one
      participant had a single renal lesion. Approximately 92% (340/371) of the adult
      study participants completed the questionnaire, which was used to identify
      factors associated with an increased risk for human infection. Age, level of
      education, dog ownership, and contact with sheep were found to be significantly
      associated with CE status. This study demonstrated that CE continues to be highly
      endemic in this region of Rio Negro Province, Argentina. In addition, community
      based ultrasound screening surveys are a noninvasive, effective approach to case
      detection at the community level. 

PMID- 24742908
TI  - Applying spatial analysis of genetic and environmental data to predict connection
      corridors to the New World screwworm populations in South America.
AB  - The myiasis causing New World screwworm (NWS) fly is responsible for substantial
      losses to livestock breeders in the Americas. Due to the negative impact of the
      NWS fly in animal health, expansion of successful NWS fly eradication programmes
      is under discussion. However, the effects of geography and environmental
      diversity on NWS population structure and migration patterns need to be assessed
      before any political decision is made to implement such a programme. We present a
      GIS tool to construct potential connection corridors among sampling localities
      based on genetic and environmental data. We integrate, through a home-made python
      script, a friction raster based on a Maxent niche model and the pairwise PhiST
      statistic. Among 38 NWS fly sampling localities from South America, we find a
      high population connectivity among the sampling localities from the south of the
      Amazon region. The region along the Atlantic Ocean was identified as the most
      probable migration corridor between the north (NAG) and the south (SAG) of the
      Amazon region. The approach highlighted previously undetected population
      structure within NAG showing low to medium connectivity through the Andes,
      correlating with current understanding of NWS fly migration in South America.
      Also, the approach is flexible, allowing future research to incorporate other
      niche simulations and genetic differentiation metrics. With this flexibility, the
      tool could become part of any AW-IPM by helping to target regions for control. 

PMID- 24742909
TI  - Time-dependent tegumental surface changes in juvenile Fasciola gigantica in
      response to triclabendazole treatment in goat.
AB  - Triclabendazole (TCBZ), the anthelmintic drug active against both mature and
      immature liver flukes, was used to investigate the effect of in vivo treatment on
      the tegumental surface of juvenile Fasciola gigantica. Five goats were infected
      with 150 F. gigantica metacercariae each by oral gavage. Four of them were
      treated with single dose of TCBZ at 10mg/kg at four weeks post-infection. They
      were euthanized at 0 (untreated), 24, 48, 72 and 96h post treatment. Juvenile
      flukes were manually retrieved from the goat livers and processed for scanning
      electron microscopy. In control flukes, the anterior region was adorned with
      sharply pointed spines projecting away from the surface, while in the posterior
      region, spines become shorter and narrower, loosing serration and with the
      appearance of distinct furrows and papillae. The dorsal surface retained the same
      pattern of surface architecture similar to that of ventral surface. Flukes
      obtained from 24h post-treatment did not show any apparent change and were still
      very active. However, there were limited movements and some blebbing, swelling,
      deposition of tegumental secretions and some flattening displayed by the flukes
      of 48h post-treatment. All the worms were found dead 72h post-treatment and
      showed advanced level of tegumental disruptions, consisting of severe distortion
      of spines, sloughing off the tegument to expose the basal lamina, formation of
      pores and isolated patches of lesions. By 96h post-treatment, the disruption was
      extremely severe and the tegument was completely sheared off causing deeper
      lesions that exposed the underlying musculature. The disruption was more severe
      at posterior than anterior region and on ventral than dorsal surface. The present
      study further establishes the time-course of TCBZ action in vivo with 100%
      efficacy against the juvenile tropical liver fluke. 

PMID- 24742910
TI  - Viral triggering of anti-NMDA receptor encephalitis in a child - an important
      cause for disease relapse.
AB  - Herpes simplex encephalitis (HSE) in children is a potentially devastating
      condition which is occasionally complicated by a clinical relapse. An autoimmune
      component has long been suspected in these relapses and recent findings suggest
      that antibodies against N-methyl-D-aspartate receptors (NMDARs) may be part of
      this mechanism. We here report an 11 months old girl with acute HSE and with
      negative NMDAR antibody serology at presentation who after an initial response to
      antiviral treatment deteriorated with seizures, abnormal movements, focal
      neurologic deficits and psychiatric symptoms. We show that this relapse occurred
      as production of NMDAR antibodies developed and that clinical improvement
      followed immunotherapy with a concomitant decrease in NMDAR antibody titers in
      CSF. She also developed a characteristic 15-20 Hz activity over both hemispheres
      which has been previously described as an electroencephalographic presentation of
      anti-NMDAR encephalitis. We conclude that relapse or persisting symptoms in HSE
      in children may represent an immune-mediated mechanism rather than a viral
      reactivation and that NMDAR antibodies should be analyzed as this may be of
      importance for the choice of therapy.

PMID- 24742911
TI  - Diagnosis by whole exome sequencing of atypical infantile onset Alexander disease
      masquerading as a mitochondrial disorder.
AB  - INTRODUCTION: There are many similarities, both clinical and radiological,
      between mitochondrial leukoencephalopathies and Alexander disease, an
      astrogliopathy. Clinically, both can manifest with a myriad of symptoms and
      signs, arising from the neonatal period to adulthood. Radiologically, both can
      demonstrate white matter changes, signal abnormalities of basal ganglia or
      thalami, brainstem abnormalities and contrast enhancement of white matter
      structures. Magnetic resonance spectroscopy may reveal elevation of lactate in
      the abnormal white matter in Alexander disease making the distinction even more
      challenging. PATIENT AND METHODS: We present a child who was considered to have
      an infantile onset mitochondrial disorder due to a combination of neurological
      symptoms and signs (developmental regression, failure to thrive, episodic
      deterioration, abnormal eye movements, pyramidal and cerebellar signs), urinary
      excretion of 3-methyl-glutaconic acid and imaging findings (extensive white
      matter changes and cerebellar atrophy) with a normal head circumference. Whole
      exome sequence analysis was performed. RESULTS: The child was found to harbor the
      R416W mutation, one of the most prevalent mutations in the glial fibrillary
      acidic protein (GFAP) gene that causes Alexander disease. CONCLUSIONS: Alexander
      disease should be considered in the differential diagnosis of infantile
      leukoencephalopathy, even when no macrocephaly is present. Next generation
      sequencing is a useful aid in unraveling the molecular etiology of
      leukoencephalopathies.

PMID- 24742913
TI  - Going against the flow: a case for peroxisomal protein export.
AB  - Peroxisomes play a crucial role in regulating cellular metabolism, providing
      compartments where metabolic pathways can be contained and controlled. Their
      importance is underlined by the developmental brain disorders caused by
      peroxisome malfunction, while disturbances in peroxisome function also contribute
      to ageing. As peroxisomes do not contain DNA, they rely on an active transport
      system to obtain the full quota of proteins required for function. Organelle
      protein transport however, is rarely a one-way process and exciting recent data
      have demonstrated that peroxisomes can selectively export membrane and matrix
      proteins to fulfil specific functions. This review will summarise the current
      knowledge on peroxisomal membrane and matrix protein export, discussing the
      mechanisms underlying export as well as the role of peroxisomal protein export in
      peroxisomal and cellular function. 

PMID- 24742914
TI  - Protein arginine methyltransferase 6 enhances ligand-dependent and -independent
      activity of estrogen receptor alpha via distinct mechanisms.
AB  - Recent studies reported that protein arginine methyltransferase 6 (PRMT6)
      enhances estrogen-induced activity of estrogen receptor alpha (ERalpha) and
      dysfunction of PRMT6 is associated with overall better survival for ERalpha
      positive breast cancer patients. However, it is unclear how PRMT6 promotes
      ERalpha activity. Here we report that PRMT6 specifically interacts with ERalpha
      at its ligand-binding domain. PRMT6 also methylates ERalpha both in vitro and in
      vivo. In addition to enhancing estrogen-induced ERalpha activity, PRMT6 over
      expression up-regulates estrogen-independent activity of ERalpha and PRMT6 gene
      silencing in MCF7 cells inhibits ligand-independent ERalpha activation. More
      interestingly, the effect of PRMT6 on the ligand-independent ERalpha activity
      does not require its methyltransferase activity. Instead, PRMT6 competes with
      Hsp90 for ERalpha binding: PRMT6 and Hsp90 bindings to ERalpha are mutually
      exclusive and PRMT6 over-expression reduces ERalpha interaction with Hsp90. In
      conclusion, PRMT6 requires its methyltransferase activity to enhance ERalpha's
      ligand-induced activity, but its effect on ligand-independent activity is likely
      mediated through competing with Hsp90 for binding to the C-terminal domain of
      ERalpha. PRMT6-ERalpha interaction would prevent ERalpha-Hsp90 association. Since
      Hsp90 and associated chaperones serve to maintain ERalpha conformation for ligand
      binding yet functionally inactive, inhibition of ERalpha-Hsp90 interaction would
      relieve ERalpha from the constraint of chaperone complex. 

PMID- 24742915
TI  - Alzheimer's disease-related plaques in nondemented subjects.
AB  - Alzheimer's disease (AD) pathology was assessed in 587 nondemented subjects, with
      age at death at or more than 50 years. In 307 subjects, amyloid-beta (Abeta)
      immunoreactive (IR) plaques were seen; in 192 subjects, neuritic plaques (NPs)
      stained with modified Bielschowsky silver stain (mBky) were observed. In 20% of
      the whole cohort and in 62% of the 192 subjects with NPs in mBky,
      hyperphosphorylated tau (HPtau) IR NPs were seen. In most cases in this
      nondemented cohort, the HPtau IR NPs were observed either sparsely or to a
      moderate extent. The correlation between the NP score and Braak stage was best
      (r=0.6, P<.001) when HPtau immunohistochemistry was used. Eighty-three percent of
      the subjects could not be categorized following the 1997 National Institute on
      Aging and the Reagan Institute (NIA-RI) recommendations, whereas the 2012
      National Institute on Aging-Alzheimer's Association (NIA-AA) guidelines were
      applicable for all study subjects. Twenty-eight subjects had an intermediate
      level of AD neuropathological change according to the 2012 NIA-AA guidelines, and
      25 of these 28 subjects displayed HPtau IR NPs in the temporal cortex. It is
      noteworthy, however, that as many as 119 out of the 192 subjects with NPs in mBky
      displayed HPtau IR NPs in the temporal cortex. Ninety-four of these 119 subjects
      with neocortical HPtau IR NPs had a low level of neuropathological AD change
      according to the 2012 NIA-AA guidelines because they were in Braak stages I and
      II. Thus, 94 subjects were not acknowledged as being at risk for AD when applying
      the 2012 NIA-AA guidelines. We suggest that to identify all subjects with
      cortical HPtau pathology and, consequently, probably being at risk for developing
      AD, in addition to the level of AD neuropathological change as recommended by the
      2012 NIA-AA guidelines, assessment of HPtau IR NPs in the neocortex should be
      carried out.

PMID- 24742916
TI  - Can diffusion kurtosis imaging improve the sensitivity and specificity of
      detecting microstructural alterations in brain tissue chronically after
      experimental stroke? Comparisons with diffusion tensor imaging and histology.
AB  - Imaging techniques that provide detailed insights into structural tissue changes
      after stroke can vitalize development of treatment strategies and diagnosis of
      disease. Diffusion-weighted MRI has been playing an important role in this
      regard. Diffusion kurtosis imaging (DKI), a recent addition to this repertoire,
      has opened up further possibilities in extending our knowledge about structural
      tissue changes related to injury as well as plasticity. In this study we sought
      to discern the microstructural alterations characterized by changes in diffusion
      tensor imaging (DTI) and DKI parameters at a chronic time point after
      experimental stroke. Of particular interest was the question of whether DKI
      parameters provide additional information in comparison to DTI parameters in
      understanding structural tissue changes, and if so, what their histological
      origins could be. Region-of-interest analysis and a data-driven approach to
      identify tissue abnormality were adopted to compare DTI- and DKI-based parameters
      in post mortem rat brain tissue, which were compared against immunohistochemistry
      of various cellular characteristics. The unilateral infarcted area encompassed
      the ventrolateral cortex and the lateral striatum. Results from region-of
      interest analysis in the lesion borderzone and contralateral tissue revealed
      significant differences in DTI and DKI parameters between ipsi- and contralateral
      sensorimotor cortex, corpus callosum, internal capsule and striatum. This was
      reflected by a significant reduction in ipsilateral mean diffusivity (MD) and
      fractional anisotropy (FA) values, accompanied by significant increases in
      kurtosis parameters in these regions. Data-driven analysis to identify tissue
      abnormality revealed that the use of kurtosis-based parameters improved the
      detection of tissue changes in comparison with FA and MD, both in terms of
      dynamic range and in being able to detect changes to which DTI parameters were
      insensitive. This was observed in gray as well as white matter. Comparison
      against immunohistochemical stainings divulged no straightforward correlation
      between diffusion-based parameters and individual neuronal, glial or inflammatory
      tissue features. Our study demonstrates that DKI allows sensitive detection of
      structural tissue changes that reflect post-stroke tissue remodeling. However,
      our data also highlights the generic difficulty in unambiguously asserting
      specific causal relationships between tissue status and MR diffusion parameters. 

PMID- 24742917
TI  - A semi-parametric nonlinear model for event-related fMRI.
AB  - Nonlinearity in evoked hemodynamic responses often presents in event-related fMRI
      studies. Volterra series, a higher-order extension of linear convolution, has
      been used in the literature to construct a nonlinear characterization of
      hemodynamic responses. Estimation of the Volterra kernel coefficients in these
      models is usually challenging due to the large number of parameters. We propose a
      new semi-parametric model based on Volterra series for the hemodynamic responses
      that greatly reduces the number of parameters and enables "information borrowing"
      among subjects. This model assumes that in the same brain region and under the
      same stimulus, the hemodynamic responses across subjects share a common but
      unknown functional shape that can differ in magnitude, latency and degree of
      interaction. We develop a computationally-efficient strategy based on splines to
      estimate the model parameters, and a hypothesis test on nonlinearity. The
      proposed method is compared with several existing methods via extensive
      simulations, and is applied to a real event-related fMRI study. 

PMID- 24742918
TI  - Simulation-based optimisation of the PET data processing for partial saturation
      approach protocols.
AB  - Positron emission tomography (PET) with [(11)C]Raclopride is an important tool
      for studying dopamine D2 receptor expression in vivo. [(11)C]Raclopride PET
      binding experiments conducted using the Partial Saturation Approach (PSA) allow
      the estimation of receptor density (B(avail)) and the in vivo affinity appK(D).
      The PSA is a simple, single injection, single scan experimental protocol that
      does not require blood sampling, making it ideal for use in longitudinal studies.
      In this work, we generated a complete Monte Carlo simulated PET study involving
      two groups of scans, in between which a biological phenomenon was inferred (a 30%
      decrease of B(avail)), and used it in order to design an optimal data processing
      chain for the parameter estimation from PSA data. The impact of spatial
      smoothing, noise removal and image resolution recovery technique on the
      statistical detection was investigated in depth. We found that image resolution
      recovery using iterative deconvolution of the image with the system point spread
      function associated with temporal data denoising greatly improves the accuracy
      and the statistical reliability of detecting the imposed phenomenon. Before
      optimisation, the inferred B(avail) variation between the two groups was
      underestimated by 42% and detected in 66% of cases, while a false decrease of
      appK(D) by 13% was detected in more than 11% of cases. After optimisation, the
      calculated B(avail) variation was underestimated by only 3.7% and detected in 89%
      of cases, while a false slight increase of appK(D) by 3.7% was detected in only
      2% of cases. We found during this investigation that it was essential to adjust a
      factor that accounts for difference in magnitude between the non-displaceable
      ligand concentrations measured in the target and in the reference regions, for
      different data processing pathways as this ratio was affected by different image
      resolutions.

PMID- 24742920
TI  - Investigation of the neurovascular coupling in positive and negative BOLD
      responses in human brain at 7 T.
AB  - Decreases in stimulus-dependent blood oxygenation level dependent (BOLD) signal
      and their underlying neurovascular origins have recently gained considerable
      interest. In this study a multi-echo, BOLD-corrected vascular space occupancy
      (VASO) functional magnetic resonance imaging (fMRI) technique was used to
      investigate neurovascular responses during stimuli that elicit positive and
      negative BOLD responses in human brain at 7 T. Stimulus-induced BOLD, cerebral
      blood volume (CBV), and cerebral blood flow (CBF) changes were measured and
      analyzed in 'arterial' and 'venous' blood compartments in macro- and
      microvasculature. We found that the overall interplay of mean CBV, CBF and BOLD
      responses is similar for tasks inducing positive and negative BOLD responses.
      Some aspects of the neurovascular coupling however, such as the temporal
      response, cortical depth dependence, and the weighting between 'arterial' and
      'venous' contributions, are significantly different for the different task
      conditions. Namely, while for excitatory tasks the BOLD response peaks at the
      cortical surface, and the CBV change is similar in cortex and pial vasculature,
      inhibitory tasks are associated with a maximum negative BOLD response in deeper
      layers, with CBV showing strong constriction of surface arteries and a faster
      return to baseline. The different interplays of CBV, CBF and BOLD during
      excitatory and inhibitory responses suggests different underlying hemodynamic
      mechanisms.

PMID- 24742921
TI  - A retrospective study of equine actinobacillosis cases: 1999-2011.
AB  - Several Actinobacillus spp. are common commensal bacteria of the oral cavity,
      gastrointestinal tract, and reproductive tract of horses and can cause disease in
      both foals and adults. The current retrospective study was designed to review
      Actinobacillus spp. isolated from clinical samples or necropsies of 99 horses
      during 1999-2011. The cases consisted of 43 foals (<6 months of age), 4 young
      adults (6 months-2 years), 39 adults (>2 years of age), 2 aborted fetuses, and 11
      with unspecified ages. Clinical history, signs, bacterial species isolated, and
      associated lesions were documented. Actinobacillus spp. were isolated 111 times.
      The most common isolates were Actinobacillus equuli subsp. equuli (38.7%) and
      hemolytic Actinobacillus spp. (24.3%). Other isolates were Actinobacillus
      lignieresii (5.4%), Actinobacillus pleuropneumoniae (1.8%), and unclassified
      Actinobacillus spp. (28.8%). Actinobacillus equuli subsp. equuli was most
      commonly isolated from clinical and necropsy cases of septicemia and respiratory
      disease in both foals and adults. Embolic nephritis, the classical septicemic
      lesion of equine neonatal actinobacillosis, was also present in several adult
      septicemic actinobacillosis cases. Predisposing factors such as failure of
      passive transfer of colostral antibodies as well as concurrent pathogenic
      bacterial or viral infections were present in numerous actinobacillosis cases.
      There were many cases, however, for which a predisposing factor or concurrent
      infection was not documented or apparent, suggesting that Actinobacillus spp. can
      be primary pathogens under the right circumstances and in the right location.

PMID- 24742919
TI  - Individualized Gaussian process-based prediction and detection of local and
      global gray matter abnormalities in elderly subjects.
AB  - Structural imaging based on MRI is an integral component of the clinical
      assessment of patients with potential dementia. We here propose an individualized
      Gaussian process-based inference scheme for clinical decision support in healthy
      and pathological aging elderly subjects using MRI. The approach aims at
      quantitative and transparent support for clinicians who aim to detect structural
      abnormalities in patients at risk of Alzheimer's disease or other types of
      dementia. Firstly, we introduce a generative model incorporating our knowledge
      about normative decline of local and global gray matter volume across the brain
      in elderly. By supposing smooth structural trajectories the models account for
      the general course of age-related structural decline as well as late-life
      accelerated loss. Considering healthy subjects' demography and global brain
      parameters as informative about normal brain aging variability affords
      individualized predictions in single cases. Using Gaussian process models as a
      normative reference, we predict new subjects' brain scans and quantify the local
      gray matter abnormalities in terms of Normative Probability Maps (NPM) and global
      z-scores. By integrating the observed expectation error and the predictive
      uncertainty, the local maps and global scores exploit the advantages of Bayesian
      inference for clinical decisions and provide a valuable extension of diagnostic
      information about pathological aging. We validate the approach in simulated data
      and real MRI data. We train the GP framework using 1238 healthy subjects with
      ages 18-94 years, and predict in 415 independent test subjects diagnosed as
      healthy controls, Mild Cognitive Impairment and Alzheimer's disease.

PMID- 24742922
TI  - Inhibition of protein kinase II (CK2) prevents induced signal transducer and
      activator of transcription (STAT) 1/3 and constitutive STAT3 activation.
AB  - The Janus kinase / signal transducer and activator of transcription (Jak/STAT)
      pathway can be activated by many different cytokines, among them all members of
      the Interleukin (IL-)6 family. Dysregulation of this pathway, resulting in its
      constitutive activation, is associated with chronic inflammation and cancer
      development. In the present study, we show that activity of protein kinase II
      (CK2), a ubiquitously expressed serine/threonine kinase, is needed for induced
      activation of STAT1 and STAT3 by IL-6 classic and trans-signaling, IL-11, IL-27,
      oncostatin M (OSM), leukemia inhibitory factor (LIF) and cardiotrophin-1 (CT-1).
      Inhibition of CK2 efficiently prevented STAT phosphorylation and inhibited
      cytokine-dependent cell proliferation in a Jak1-dependent manner. Conversely,
      forced activation of CK2 alone was not sufficient to induce activation of the
      Jak/STAT signaling pathway. Inhibition of CK2 in turn inhibited Jak1-dependent
      STAT activation by oncogenic gp130 mutations. Furthermore, CK2 inhibition
      diminished the Jak1- and Src kinase-dependent phosphorylation of a constitutively
      active STAT3 mutant recently described in human large granular lymphocytic
      leukemia. In conclusion, we characterize CK2 as an essential component of the
      Jak/STAT pathway. Pharmacologic inhibition of this kinase is therefore a
      promising strategy to treat human inflammatory diseases and malignancies
      associated with constitutive activation of the Jak/STAT pathway. 

PMID- 24742923
TI  - Mapping of actionable mutations to histological subtype domains in lung
      adenocarcinoma: implications for precision medicine.
AB  - Precision medicine depends on the accurate identification of actionable mutations
      in a tumor sample. It is unknown how heterogeneous the distribution of such
      mutations can be in a tumor. Morphological (i.e. histopathological) heterogeneity
      is well described in lung adenocarcinoma and has been specifically recognized in
      the most recent official clinico-pathological classification. The most
      predominant subtype present is now used to classify each lung adenocarcinoma. No
      molecular profile exists to explain the intratumoral differences in lung
      adenocarcinoma morphology, despite the consistently observed association between
      specific predominant subtypes and poorer survival. Given a recent proposal
      stratifying lung adenocarcinoma into subtypes of differing metastatic potential,
      we questioned the assumption that major mutations are present uniformly
      throughout tumors; especially those showing discrete different subtypes. We
      selected formalin-fixed paraffin embedded lung adenocarcinoma specimens that
      showed discrete areas of different subtypes, extracted subtype DNA samples from
      those areas and screened for mutations in hotspot regions of the EGFR, KRAS and
      BRAF genes using high resolution melting. Sanger sequencing was used to confirm
      all identified mutations. Chromogenic in situ hybridization (CISH) was used to
      identify mutant allele specific imbalances in tumors with EGFR mutations.
      Interestingly, we found that KRAS and BRAF mutations could be confined to
      morphological domains of higher grade. On the other hand, EGFR mutations were
      found through all histological subtypes in each tumor consistent with the driver
      status of this mutation. Intratumoral heterogeneity has major implications for
      tumorigenesis, chemoresistance and the role of histopathology in molecular
      screening for precision medicine. This study not only confirms that intratumoral
      mutational heterogeneity does occur, but also that it is associated with
      morphologically distinct regions in some tumors. From a practical perspective,
      small biopsies may not adequately represent a tumor's full mutational profile,
      particularly for later arising but prognostically important mutations such as
      those in the KRAS and BRAF genes. 

PMID- 24742924
TI  - G protein-coupled receptor 56 regulates matrix production and motility of lung
      fibroblasts.
AB  - Idiopathic pulmonary fibrosis is a chronic, progressive, and fatal fibrotic lung
      disease with a poor prognosis, but no effective treatment is available. G protein
      coupled receptor 56 (GPR56) plays a role in cell adhesion and tumor progression,
      but its function in fibrogenesis has not been explored. In this in vitro study,
      we found that GPR56 in IPF fibroblasts was lower than in normal fibroblasts.
      GPR56 regulated the production of fibronectin and type I collagen, and also
      changed the migratory and invasive capacity of lung fibroblasts. However, it was
      not sufficient to activate some classic markers of fibroblast and myofibroblast,
      such as alpha-smooth muscle actin and fibroblast specific protein 1. These
      findings demonstrate that reduced expression of GPR56 in lung fibroblasts may be
      an important link with pulmonary fibrosis, playing a role in regulating some
      important fibroblast functions.

PMID- 24742925
TI  - Hippocampal volume is inversely related to PTSD duration.
AB  - Numerous imaging studies have reported smaller hippocampal volumes in patients
      with PTSD. To investigate whether decreased hippocampal volume is associated with
      PTSD chronicity, independent of age, we used hierarchical linear regression to
      examine the relationship between PTSD duration (estimated from the amount of time
      that had elapsed since the traumatic event; mean=17 years; range=6-36 years) and
      hippocampal volume, adjusting for age and other factors. Freesurfer version 4.5
      was used to quantify the volumes of the hippocampus and the caudate nucleus,
      which served as a "control" region, from the 1.5T Magnetic Resonance Images (MRI)
      of 55 combat veterans (mean age 45+/-9 years) with chronic and current PTSD. PTSD
      duration was significantly associated with right hippocampal volume (beta=-0.34,
      t=-2.40, P=0.02) after accounting for intracranial volume, age, gender (entered
      in the first step) and comorbidities (e.g., early life trauma, current major
      depression, history of substance abuse/dependence, psychotropic medication use,
      entered in the second step). This finding provides support for the potential
      neurotoxic effects of PTSD on hippocampal volume. 

PMID- 24742926
TI  - Ultrastructural features of the benthic dinoflagellate Ostreopsis cf. ovata
      (Dinophyceae).
AB  - The toxic benthic dinoflagellate Ostreopsis cf. ovata has considerably expanded
      its distribution range in the last decade, posing risks to human health. Several
      aspects of this species are still poorly known. We studied ultrastructural
      features of cultivated and natural populations of Ostreopsis cf. ovata from the
      Gulf of Naples (Mediterranean Sea) using confocal laser scanning, and scanning
      and transmission electron microscopy. New information on the morphology and
      location of several sulcal plates was gained and a new plate designation is
      suggested that better fits the one applied to other Gonyaulacales. The
      microtubular component of the cytoskeleton, revealed using an anti-beta-tubulin
      antibody, consisted of a cortical layer of microtubules arranged asymmetrically
      in the episome and in the hyposome, complemented by a complex inner microtubular
      system running from the sulcal area towards the internal part of the cell. The
      conspicuous canal was delimited by two thick, burin-shaped lobes ending in a
      tubular ventral opening. The canal was surrounded by mucocysts discharging their
      content into it. A similar structure has been reported in other benthic and
      planktonic dinoflagellates and may be interpreted as an example of convergent
      evolution in species producing large amounts of mucus.

PMID- 24742928
TI  - Autoecological approaches to resolve subjective taxonomic divisions within
      arcellacea.
AB  - Arcellacea (testate lobose amoebae) are important lacustrine environmental
      indicators that have been used in paleoclimatic reconstructions, assessing the
      effectiveness of mine tailings pond reclamation projects and for studying the
      effects of land use change in rural, industrial and urban settings. Recognition
      of ecophenotypically significant infra-specific 'strains' within arcellacean
      assemblages has the potential to enhance the utility of the group in
      characterizing contemporary and paleoenvironments. We present a novel approach
      which employs statistical tools to investigate the environmental and taxonomic
      significance of proposed strains. We test this approach on two identified
      strains: Difflugia protaeiformis Lamarck strain 'acuminata' (DPA), characterized
      by fine grained agglutination, and Difflugia protaeiformis Lamarck strain
      'claviformis' (DPC), characterized by coarse grained agglutination. Redundancy
      analysis indicated that both organisms are associated with similar environmental
      variables. No relationship was observed between substrate particle size and
      abundance of DPC, indicating that DPC has a size preference for xenosomes during
      test construction. Thus DPC should not be designated as a distinct strain but
      rather form a species complex with DPA. This study elucidates the need to justify
      the designation of strains based on their autecology in addition to morphological
      stability.

PMID- 24742929
TI  - Special Issue. Testing the waters: a selection of papers from the first
      international multidisciplinary conference on detecting illicit drugs in
      wastewater.

PMID- 24742927
TI  - Tritrichomonas foetus displays classical detergent-resistant membrane
      microdomains on its cell surface.
AB  - Tritrichomonas foetus is a serious veterinary parasite that causes bovine
      trichomoniasis, a sexually transmitted disease that results in reproductive
      failure and considerable economic losses in areas that practice natural breeding.
      T. foetus is an extracellular parasite, which initially adheres to and infects
      the urogenital tract using a diverse array of surface glycoconjugates, including
      adhesins and extracellular matrix-binding molecules. However, the cellular
      mechanisms by which T. foetus colonizes mucosal surfaces and causes tissue damage
      are not well defined. Several studies have demonstrated the involvement of
      pathogen or host lipid rafts in cellular events that occur during pathogenesis,
      including adhesion, invasion and evasion of the immune response. In this study,
      we demonstrate that detergent-resistant membranes are present in the plasma
      membrane of T. foetus. We further demonstrate that microdomains are cholesterol
      enriched and contain ganglioside GM1-like molecules. In addition, we demonstrate
      that lipid microdomains do not participate in T. foetus adhesion to host cells.
      However, the use of agents that disrupt and disorganize the plasma membrane
      indicated the involvement of the T. foetus lipid microdomains, in cell division
      and in the formation of endoflagellar forms. Our results suggest that
      trophozoites and endoflagellar forms present a different plasma membrane
      organization.

PMID- 24742931
TI  - Acquired Thrombophilia.
AB  - Acquired thrombophilia is associated with an increased risk of venous
      thromboembolism (VTE). Antiphospholipid syndrome (APS) is the most prevalent
      acquired thrombophilia and is associated with both venous and arterial
      thromboses. Human immunodeficiency virus (HIV) is another form of acquired
      thrombophilia. Risk factors associated with VTE in this population include those
      related to the disease itself, host factors, and the pharmacotherapy for HIV. A
      significant proportion of VTE events occur in patients with malignancies. There
      is an increase in mortality associated with patients having cancer who experience
      VTE when compared to patients having cancer without VTE. Combination oral
      contraceptive (COC) use infers risk of thromboembolic events. The risk is
      dependent upon the presence of an underlying inherited thrombophilia, the
      estrogen dose, and generation of progestin. Patients at highest risk of VTE
      include those receiving high-dose estrogen and fourth-generation, progesterone
      containing contraceptives. With the exception of APS, thrombophilia status does
      not alter the acute treatment of an initial VTE in nonpregnant patients. 

PMID- 24742930
TI  - Update of the German Diabetes Risk Score and external validation in the German
      MONICA/KORA study.
AB  - AIMS: Several published diabetes prediction models include information about
      family history of diabetes. The aim of this study was to extend the previously
      developed German Diabetes Risk Score (GDRS) with family history of diabetes and
      to validate the updated GDRS in the Multinational MONItoring of trends and
      determinants in CArdiovascular Diseases (MONICA)/German Cooperative Health
      Research in the Region of Augsburg (KORA) study. METHODS: We used data from the
      European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam study
      for extending the GDRS, including 21,846 participants. Within 5 years of follow
      up 492 participants developed diabetes. The definition of family history included
      information about the father, the mother and/or sibling/s. Model extension was
      evaluated by discrimination and reclassification. We updated the calculation of
      the score and absolute risks. External validation was performed in the
      MONICA/KORA study comprising 11,940 participants with 315 incident cases after 5
      years of follow-up. RESULTS: The basic ROC-AUC of 0.856 (95%-CI: 0.842-0.870) was
      improved by 0.007 (0.003-0.011) when parent and sibling history was included in
      the GDRS. The net reclassification improvement was 0.110 (0.072-0.149),
      respectively. For the updated score we demonstrated good calibration across all
      tenths of risk. In MONICA/KORA, the ROC-AUC was 0.837 (0.819-0.855); regarding
      calibration we saw slight overestimation of absolute risks. CONCLUSIONS:
      Inclusion of the number of diabetes-affected parents and sibling history improved
      the prediction of type 2 diabetes. Therefore, we updated the GDRS algorithm
      accordingly. Validation in another German cohort study showed good discrimination
      and acceptable calibration for the vast majority of individuals.

PMID- 24742932
TI  - Pregnancy-Related Venous Thromboembolism.
AB  - Pregnancy is associated with an increased risk of venous thromboembolism (VTE),
      with a reported incidence ranging from 0.49 to 2 events per 1000 deliveries. Risk
      factors include advanced maternal age, obesity, smoking, and cesarian section.
      Women with a history of previous VTE are at a 4-fold higher risk of recurrent
      thromboembolic events during subsequent pregnancies. Additionally, the presence
      of concomitant thrombophilia, particularly factor V Leiden (homozygosity),
      prothrombin gene mutation (homozygosity), or antiphospholipid syndrome (APS),
      increases the risk of pregnancy-related VTE. Low-molecular-weight heparin (LMWH)
      and unfractionated heparin (UFH) are the drugs of choice for anticoagulation
      during pregnancy. LMWH is preferred due to ease of use and lower rates of adverse
      events. Women with high thromboembolic risk particularly those with a family
      history of VTE should receive antepartum thromboprophylaxis. Women with low
      thromboembolic risk or previous VTE caused by a transient risk factor (ie,
      provoked), who have no family history of VTE, may undergo antepartum
      surveillance. Postpartum anticoagulation can be considered in women with both
      high and low thromboembolic risk. 

PMID- 24742933
TI  - Structural dynamics of a single-stranded RNA-helix junction using NMR.
AB  - Many regulatory RNAs contain long single strands (ssRNA) that adjoin secondary
      structural elements. Here, we use NMR spectroscopy to study the dynamic
      properties of a 12-nucleotide (nt) ssRNA tail derived from the prequeuosine
      riboswitch linked to the 3' end of a 48-nt hairpin. Analysis of chemical shifts,
      NOE connectivity, (13)C spin relaxation, and residual dipolar coupling data
      suggests that the first two residues (A25 and U26) in the ssRNA tail stack onto
      the adjacent helix and assume an ordered conformation. The following U26-A27 step
      marks the beginning of an A6-tract and forms an acute pivot point for substantial
      motions within the tail, which increase toward the terminal end. Despite
      substantial internal motions, the ssRNA tail adopts, on average, an A-form
      helical conformation that is coaxial with the helix. Our results reveal a
      surprising degree of structural and dynamic complexity at the ssRNA-helix
      junction, which involves a fine balance between order and disorder that may
      facilitate efficient pseudoknot formation on ligand recognition. 

PMID- 24742934
TI  - RNA secondary structure modeling at consistent high accuracy using differential
      SHAPE.
AB  - RNA secondary structure modeling is a challenging problem, and recent successes
      have raised the standards for accuracy, consistency, and tractability. Large
      increases in accuracy have been achieved by including data on reactivity toward
      chemical probes: Incorporation of 1M7 SHAPE reactivity data into an mfold-class
      algorithm results in median accuracies for base pair prediction that exceed 90%.
      However, a few RNA structures are modeled with significantly lower accuracy.
      Here, we show that incorporating differential reactivities from the NMIA and 1M6
      reagents--which detect noncanonical and tertiary interactions--into prediction
      algorithms results in highly accurate secondary structure models for RNAs that
      were previously shown to be difficult to model. For these RNAs, 93% of accepted
      canonical base pairs were recovered in SHAPE-directed models. Discrepancies
      between accepted and modeled structures were small and appear to reflect genuine
      structural differences. Three-reagent SHAPE-directed modeling scales concisely to
      structurally complex RNAs to resolve the in-solution secondary structure analysis
      problem for many classes of RNA.

PMID- 24742935
TI  - Non-nearest-neighbor dependence of stability for group III RNA single nucleotide
      bulge loops.
AB  - Thirty-five RNA duplexes containing single nucleotide bulge loops were optically
      melted and the thermodynamic parameters for each duplex determined. The bulge
      loops were of the group III variety, where the bulged nucleotide is either a AG/U
      or CU/G, leading to ambiguity to the exact position and identity of the bulge.
      All possible group III bulge loops with Watson-Crick nearest-neighbors were
      examined. The data were used to develop a model to predict the free energy of an
      RNA duplex containing a group III single nucleotide bulge loop. The
      destabilization of the duplex by the group III bulge could be modeled so that the
      bulge nucleotide leads to the formation of the Watson-Crick base pair rather than
      the wobble base pair. The destabilization of an RNA duplex caused by the
      insertion of a group III bulge is primarily dependent upon non-nearest-neighbor
      interactions and was shown to be dependent upon the stability of second least
      stable stem of the duplex. In-line structure probing of group III bulge loops
      embedded in a hairpin indicated that the bulged nucleotide is the one positioned
      further from the hairpin loop irrespective of whether the resulting stem formed a
      Watson-Crick or wobble base pair. Fourteen RNA hairpins containing group III
      bulge loops, either 3' or 5' of the hairpin loop, were optically melted and the
      thermodynamic parameters determined. The model developed to predict the influence
      of group III bulge loops on the stability of duplex formation was extended to
      predict the influence of bulge loops on hairpin stability. 

PMID- 24742936
TI  - miR-19b promotes tumor growth and metastasis via targeting TP53.
AB  - Tumor suppressor TP53 (or p53) is one of the most important regulators in
      numerous physiological and pathological processes. Recently, the miRNA-mediated
      post-transcription regulation of p53 has been studied. However, systematic
      studies of miRNA targeting sites within the p53 gene are still a challenging
      task. Here, we developed a dual-color assay capable of identifying miRNA
      targeting sites in a certain gene, specifically p53, in a simple, direct, and
      robust manner. Results showed that p53 was a direct and critical target of miR
      19b, but not miR-19a, regardless of sequence similarity. Overexpression of miR
      19b observed in human cancer cells can diminish p53 protein levels and,
      subsequently, downstream components such as Bax and p21. This miR-19b-mediated
      p53 reduction was shown to promote cell cycle, cell migration or invasion, and
      repress senescence and apoptosis in vitro. Further investigation revealed that
      miR-19b controls tumor growth and metastasis in vivo. Therefore, it is possible
      that miR-19b antagomirs or sponges could be developed as therapeutic agents
      against tumor development. 

PMID- 24742937
TI  - Diagnostic accuracy of the electromyography parameters associated with anterior
      knee pain in the diagnosis of patellofemoral pain syndrome.
AB  - OBJECTIVE: To assess the diagnostic accuracy of the surface electromyography
      (sEMG) parameters associated with referred anterior knee pain in diagnosing
      patellofemoral pain syndrome (PFPS). DESIGN: Sensitivity and specificity
      analysis. SETTING: Physical rehabilitation center and laboratory of biomechanics
      and motor control. PARTICIPANTS: Pain-free subjects (n=29) and participants with
      PFPS (n=22) selected by convenience. INTERVENTIONS: Not applicable. MAIN OUTCOME
      MEASURE: The diagnostic accuracy was calculated for sEMG parameters' reliability,
      precision, and ability to differentiate participants with and without PFPS. The
      selected sEMG parameter associated with anterior knee pain was considered as an
      index test and was compared with the reference standard for the diagnosis of
      PFPS. Intraclass correlation coefficient, SEM, independent t tests, sensitivity,
      specificity, negative and positive likelihood ratios, and negative and positive
      predictive values were used for the statistical analysis. RESULTS: The medium
      frequency band (B2) parameter was reliable (intraclass correlation
      coefficient=.80-.90), precise (SEM=2.71-3.87 normalized unit), and able to
      differentiate participants with and without PFPS (P<.05). The association of B2
      with anterior knee pain showed positive diagnostic accuracy values (specificity,
      .87; sensitivity, .70; negative likelihood ratio, .33; positive likelihood ratio,
      5.63; negative predictive value, .72; and positive predictive value, .86).
      CONCLUSIONS: The results provide evidence to support the use of EMG signals (B2
      frequency band of 45-96 Hz) of the vastus lateralis and vastus medialis muscles
      with referred anterior knee pain in the diagnosis of PFPS.

PMID- 24742939
TI  - Improvement of upper extremity motor control and function after home-based
      constraint induced therapy in children with unilateral cerebral palsy: immediate
      and long-term effects.
AB  - OBJECTIVE: To investigate the long-term effects of home-based constraint induced
      therapy (CIT) on motor control underlying functional change in children with
      unilateral cerebral palsy (CP). DESIGN: Randomized controlled trial. SETTING:
      Home based. PARTICIPANTS: Children with unilateral CP (N=45; aged 6-12 y) were
      randomly assigned to receive home-based CIT (n=23) or traditional rehabilitation
      (TR) (n=22). INTERVENTIONS: Both groups received a 4-week therapist-based
      intervention at home. The home-based CIT involved intensive functional training
      of the more affected upper extremity during which the less affected one was
      restrained. The TR involved functional unimanual and bimanual training. MAIN
      OUTCOME MEASURES: All children underwent kinematic and clinical assessments at
      baseline, 4 weeks (posttreatment), and 3 and 6 months (follow-up). The reach-to
      grasp kinematics were reaction time (RT), normalized movement time, normalized
      movement unit, peak velocity (PV), maximum grip aperture (MGA), and percentage of
      movement where MGA occurs. The clinical measures were the Peabody Developmental
      Motor Scales, Second Edition (PDMS-2), Bruininks-Oseretsky Test of Motor
      Proficiency (BOTMP), and Functional Independence Measure for children (WeeFIM).
      RESULTS: The home-based CIT group showed a shorter RT (P<.05) and normalized
      movement time (P<.01), smaller MGA (P=.006), and fewer normalized movement units
      (P=.014) in the reach-to-grasp movements at posttreatment and follow-up than the
      TR group. The home-based CIT group improved more on the PDMS-2 (P<.001) and
      WeeFIM (P<.01) in all posttreatment tests and on the BOTMP (P<.01) at follow-up
      than the TR group. CONCLUSIONS: The home-based CIT induced better spatial and
      temporal efficiency (smoother movement, more efficient grasping, better movement
      preplanning and execution) for functional improvement up to 6 months after
      treatment than TR.

PMID- 24742938
TI  - Psychometric properties of the Brief Fatigue Inventory in community-dwelling
      older adults.
AB  - OBJECTIVE: To investigate the psychometric properties of the Brief Fatigue
      Inventory (BFI) in community-dwelling older adults. DESIGN: Cross-sectional
      validation study. SETTING: Community based. PARTICIPANTS: Subjects (N=302) were
      nondemented older adults (mean age, 76.44 y; 54% women). INTERVENTIONS: Not
      applicable. MAIN OUTCOME MEASURES: BFI total, severity, and interference
      summation scores. RESULTS: A principal component analysis (PCA) yielded 2
      factors, fatigue severity and interference, explaining 65.94% of the variance.
      Both factors had good reliability, with Cronbach alpha values of .867 for fatigue
      interference and .818 for fatigue severity. Higher fatigue scores were associated
      with older age and worse physical and cognitive functions. CONCLUSIONS: Fatigue
      is a common and debilitating symptom in the aging population. The current study
      provides novel findings in validating and establishing a bidimensional factor
      structure for the BFI in older adults. Severity and interference were
      differentially related to important health outcomes; therefore, using these
      subscales in addition to the total BFI score is recommended with older adults.
      Because of its relatively short administration time and established psychometric
      properties, the BFI can be successfully incorporated into longitudinal studies
      and clinical trials.

PMID- 24742940
TI  - Life-Space Assessment and Physical Activity Scale for the Elderly: validity of
      proxy informant responses.
AB  - OBJECTIVE: To validate the administration of the Life-Space Assessment (LSA) and
      Physical Activity Scale for the Elderly (PASE) surveys to proxy informants, as
      would be necessary when measuring long-term outcomes in acutely ill, hospitalized
      older adults who are initially incapacitated but eventually return to the
      community. DESIGN: Cross-sectional study. SETTING: General community.
      PARTICIPANTS: Convenience sample of dyads (N=40) composed of an ambulatory older
      adult and a familiar companion. INTERVENTIONS: Dyads completed the LSA and PASE
      surveys on 1 occasion. Companions based their responses on the recent mobility
      and physical activity of the older adult. MAIN OUTCOME MEASURES: Paired total
      scores for each instrument. RESULTS: At a group level, the difference between
      older adult and companion mean scores for each instrument was not significant
      (P>.05). Standardized mean difference values were small (d<0.1). Paired scores
      were significantly yet moderately associated: intraclass correlation
      coefficient(1,1)=.84 to .88; P<.01. Difference in scores was not associated with
      time spent together (P>.05) or older adult gait speed (P>.05). At an individual
      level, older adults and companions agreed more closely on the LSA than on the
      PASE. However, disagreement in excess of estimated measurement error occurred in
      40% of the dyads for the LSA and in none of the dyads for the PASE. CONCLUSIONS:
      Older adults and companions collectively provided similar responses on each
      instrument. Nonetheless, varying levels of agreement within individual dyads
      suggested that proxy responses should be considered carefully. Implications for
      clinical research and practice research are discussed.

PMID- 24742941
TI  - Waist circumference provides an indication of numerous cardiometabolic risk
      factors in adults with cerebral palsy.
AB  - OBJECTIVE: To report the prevalence of cardiometabolic risk factors in a cohort
      of adults with cerebral palsy (CP) and to investigate the ability of
      anthropometric measures to predict these factors. DESIGN: Cross-sectional study.
      SETTING: Testing took place in a laboratory setting. PARTICIPANTS: Adults with CP
      (N=55; mean age, 37.5+/-13.3 y; Gross Motor Function Classification System
      levels, I-V) participated in this study. INTERVENTIONS: Not applicable. MAIN
      OUTCOME MEASURES: Total cholesterol, high-density lipoprotein cholesterol, low
      density lipoprotein cholesterol, triglycerides, glucose, insulin, and C-reactive
      protein levels were measured from a fasting venous blood sample. Insulin
      resistance was calculated using the Homeostasis Model Assessment (HOMA-IR) index.
      Blood pressure, body mass index (BMI), waist circumference (WC), waist-hip ratio,
      and waist-height ratio were also measured. The metabolic syndrome (MetS) was
      defined according to the 2009 Joint Interim Statement. RESULTS: The prevalence of
      the MetS was 20.5% in ambulatory adults and 28.6% in nonambulatory adults. BMI
      was associated with HOMA-IR only (beta=.451; P<.01). WC was associated with HOMA
      IR (beta=.480; P<.01), triglycerides (beta=.450; P<.01), and systolic blood
      pressure (beta=.352; P<.05). Receiver operating characteristic curve analysis
      revealed that WC provided the best indication of hypertensive blood pressure,
      dyslipidemia, HOMA-IR, and the presence of multiple risk factors (area under the
      curve, .713-.763). CONCLUSIONS: A high prevalence of the MetS was observed in
      this relatively young sample of adults with CP. WC was a better indicator of a
      number of risk factors than was BMI and presents as a clinically useful method of
      screening for cardiometabolic risk among adults with CP.

PMID- 24742942
TI  - Mortality in South Asians and Caucasians after percutaneous coronary intervention
      in the United Kingdom: an observational cohort study of 279,256 patients from the
      BCIS (British Cardiovascular Intervention Society) National Database.
AB  - OBJECTIVES: The purpose of this study was to compare baseline characteristics and
      medium-term prognosis in South Asian and Caucasian patients undergoing
      percutaneous coronary intervention (PCI). BACKGROUND: It is unclear whether South
      Asians undergoing PCI have worse outcomes than Caucasians. METHODS: We performed
      a retrospective analysis of 279,256 patients undergoing PCI from 2004 to 2011
      from the British Cardiovascular Intervention Society national database, of whom
      259,318 (92.9%) were Caucasian and 19,938 (7.1%) were South Asian (South Asian
      includes patients of Pakistani, Indian, Bangladeshi, or Sri Lankan ethnic
      origin). The main outcome measures were in-hospital major adverse cardiac and
      cerebrovascular events and all-cause mortality during a median follow-up of 2.8
      years (interquartile range: 1.5 to 4.5 years). RESULTS: South Asians were younger
      (59.69 +/- 0.27 years vs. 64.69 +/- 0.13 years, p > 0.0001); more burdened by
      cardiovascular risk factors, particularly diabetes mellitus (42.1 +/- 1.2% vs.
      15.4 +/- 0.4%, p > 0.0001); and more likely to have multivessel coronary disease
      than Caucasians. In-hospital rates of major adverse cardiac and cerebrovascular
      events were similar for South Asians and Caucasians (3.5% vs. 2.8%, p = 0.40).
      Unadjusted Kaplan-Meier estimates of all-cause mortality showed better survival
      for South Asians compared with Caucasians, after PCI for either acute myocardial
      infarction or angina. Age-adjusted analysis revealed increased mortality (hazard
      ratio: 1.24; 95% confidence interval: 1.18 to 1.30), but after adjustment for the
      substantial variation in baseline risk factors including diabetes, there was no
      significant difference between South Asians and Caucasians (hazard ratio: 0.99;
      95% confidence interval: 0.94 to 1.05). CONCLUSIONS: In this large, contemporary
      cohort of patients treated by PCI, South Asians were younger but had more
      extensive disease and major risk factors, particularly diabetes. However, after
      correcting for these differences, in-hospital and medium-term mortality of South
      Asians was no worse than that of Caucasians. This suggests that in South Asians,
      the high prevalence of diabetes exerts an adverse influence on mortality, but
      ethnicity itself is not an independent predictor of outcome.

PMID- 24742943
TI  - Impact of smoking status in patients with non-ST-segment elevation myocardial
      infarction: the reverse smoker's paradox.

PMID- 24742944
TI  - Platelet reactivity is preferred over genotyping in monitoring efficacy of
      antiplatelet therapy.

PMID- 24742946
TI  - Is participation in clinical research a duty?

PMID- 24742945
TI  - Reply: Platelet reactivity is preferred over genotyping in monitoring efficacy of
      antiplatelet therapy.

PMID- 24742947
TI  - Successful transcatheter aortic valve replacement in a patient with a sinus of
      Valsalva aneurysm.

PMID- 24742948
TI  - Enterotoxigenic Escherichia coli infection induces intestinal epithelial cell
      autophagy.
AB  - The morbidity and mortality in piglets caused by enterotoxigenic Escherichia coli
      (ETEC) results in large economic losses to the swine industry, but the precise
      pathogenesis of ETEC-associated diseases remains unknown. Intestinal epithelial
      cell autophagy serves as a host defense against pathogens. We found that ETEC
      induced autophagy, as measured by both the increased punctae distribution of GFP
      LC3 and the enhanced conversion of LC3-I to LC3-II. Inhibiting autophagy resulted
      in decreased survival of IPEC-1 cells infected with ETEC. ETEC triggered
      autophagy in IPEC-1 cells through a pathway involving the mammalian target of
      rapamycin (mTOR), the extracellular signal-regulated kinases 1/2 (ERK1/2), and
      the AMP-activated protein kinase (AMPK). 

PMID- 24742949
TI  - The first caprine rotavirus detected in Argentina displays genomic features
      resembling virus strains infecting members of the Bovidae and Camelidae.
AB  - Rotavirus group A (RVA) is a major cause of diarrhea in humans and young animals
      including small ruminants. The purpose of this study was to identify RVA in dairy
      goat kids, and to characterize the complete genomic constellation and genetic
      relatedness with other RVA strains. Four out of twenty fecal samples from
      diarrheic and non-diarrheic goat kids were positive for RVA by ELISA. A
      representative sample was selected for further genome analyses. The RVA strain
      RVA/Goat-wt/ARG/0040/2011/G8P[1] displayed the following genomic constellation:
      G8-P[1]-I2-R5-C2-M2-A3-N2-T6-E12-H3, reminiscent to guanaco and other bovine-like
      RVA strains detected in Argentina. Phylogenetic analyses revealed that most of
      the genome segments had a rather close relatedness with RVA strains typically
      obtained from cattle, sheep, South American camelids and goats. Interestingly,
      strain 0040 possessed the R5 and E12 genotypes which have up to date only been
      found in different animal species from Argentina. Overall, these findings suggest
      that strain 0040 could represent a typical goat RVA genome constellation similar
      to those previously found in other animal species within the order Artiodactyla. 

PMID- 24742950
TI  - Molecular characterization of border disease virus strain Aveyron.
AB  - For the pestivirus border disease virus (BDV) at least seven major genotypes have
      been described (BDV-1-BDV-7). So far, complete genomic sequences have been
      reported for four BDV genotypes (BDV-1-BDV-4). In this study we report the entire
      genomic sequence of the noncytopathogenic (ncp) BDV-5 reference strain Aveyron.
      The viral genome encompasses 12,284 nucleotides (nt) and contains one large open
      reading frame (11,700 nt) flanked by a 370 nt long 5'-untranslated region (UTR)
      and a 214 nt long 3'-UTR. The genome organization as well as the lengths of the
      viral polyprotein (3899 amino acids) and the 5'-UTR are very similar to the ones
      of other BDV strains, while the 3'-UTR of BDV Aveyron is considerably shorter
      when compared to other BDV strains. Comparative analysis of complete coding
      sequences revealed that BDV Aveyron shares nucleotide sequence identities of
      76.9% to 79.0% with the other BDV strains, and less than 72% identity with other
      pestiviruses. In contrast to other BDV strains, a unique insertion of four amino
      acids (KAPD) of unknown origin is present in the C-terminal part of the viral
      autoprotease NS2 encoded by BDV Aveyron. Immunoblot analysis revealed that
      infection of cells with the ncp BDV strain Aveyron comprising this unique
      insertion in NS2 resulted in the expression of high amounts of NS3 and thereby
      showed that BDV Aveyron significantly differs from other ncp BDV strains in terms
      of NS2-3 processing and production of NS3.

PMID- 24742951
TI  - Effects of virulent and attenuated transmissible gastroenteritis virus on the
      ability of porcine dendritic cells to sample and present antigen.
AB  - Virulent transmissible gastroenteritis virus (TGEV) results in an acute, severe
      pathology and high mortality in piglets, while attenuated TGEV only causes
      moderate clinical reactions. Dendritic cells (DCs), through uptake and
      presentation of antigens to T cells, initiate distinct immune responses to
      different infections. In this study, an attenuated TGEV (STC3) and a virulent
      TGEV (SHXB) were used to determine whether porcine DCs play an important role in
      pathogenetic differences between these two TGEVs. Our results showed that
      immature and mature monocyte-derived dendritic cells (Mo-DCs) were susceptible to
      infection with SHXB and STC3. However, only SHXB inhibited Mo-DCs to activate T
      cell proliferation by down-regulating the expression of cell-surface markers and
      the secretion of cytokines in vitro. In addition, after 48 h of SHXB infection,
      there was the impairment in the ability of porcine intestinal DCs to sample the
      antigen, to migrate from the villi to the lamina propria and to activate T-cell
      proliferation in vivo. In contrast, these abilities of intestinal DCs were
      enhanced in STC3-infected piglets. In conclusion, our results show that SHXB
      significantly impaired the functions of Mo-DCs and intestinal DCs in vitro and in
      vivo, while STC3 had the opposite effect. These differences may underlie the
      pathogenesis of virulent and attenuated TGEV in piglets, and could help us to
      develop a better strategy to prevent virulent TGEV infection.

PMID- 24742952
TI  - Virulence genotypes, antibiotic resistance and the phylogenetic background of
      extraintestinal pathogenic Escherichia coli isolated from urinary tract
      infections of dogs and cats in Brazil.
AB  - Urinary tract infection (UTI) is a frequent disease of humans and pets and has
      extra-intestinal pathogenic Escherichia coli (ExPEC) strains as one of the main
      etiologic agent. ExPEC are characterized by specific virulence factors and are
      related to a heterogeneous group of human and animal disorders, besides to be a
      relevant participant in the dissemination of antimicrobial resistance. The
      purpose of this study was to characterize E. coli strains isolated from UTI of
      dogs and cats for serotypes, virulence markers, phylogenetic groups and
      sensitivity to antimicrobial drugs. E. coli was identified as the etiologic agent
      of UTI in urine samples of 43 pets (7 cats and 36 dogs). Serogroups O2, O4 and O6
      corresponded to more than one third of the isolates, being 62% of the total
      strains classified as B2, 18% as D, 16% as B1 and 4% as A. The iucD (22%), fyuA
      (80%), traT (51%) and cvaC (20%) genes were distributed among the four
      phylogenetic groups, whereas the papC/papEF (47%) and malX (67%) genes were found
      only in groups B2 and D. There were a high number of resistant strains, with 76%
      of the strains belonging to groups A, B1 and D characterized as multidrug
      resistant (MDR), whereas only 21% had this phenotype in the group B2. The ExPEC
      strains isolated in this study displayed pathotypic and phylogenetic similarities
      with human isolates and high percentages of drug resistance. The finding of MDR
      ExPEC strains suggests implications for animal and public health and deserves
      more investigations.

PMID- 24742953
TI  - Preparation, characterization and in vitro antiviral activity evaluation of
      foscarnet-chitosan nanoparticles.
AB  - A new nanoparticulate system for foscarnet delivery was prepared and evaluated.
      Nanoparticles were obtained by ionotropic gelation of chitosan induced by
      foscarnet itself, acting as an ionotropic agent in a manner similar to
      tripolyphosphate anion. A Doehlert design allowed finding the suitable
      experimental conditions. Nanoparticles were between 200 and 300nm in diameter
      (around 450nm after redispersion). Nanoparticle size increased after 5h, but no
      size increase was observed after 48h when nanoparticles were crosslinked with
      glutaraldehyde. Zeta potential values of noncrosslinked and crosslinked
      nanoparticles were between 20 and 25mV, while drug loading of noncrosslinked
      nanoparticles was about 40% w/w (55% w/w for crosslinked nanoparticles).
      Nanoparticle yield was around 25% w/w. Crosslinked nanoparticles showed a
      controlled drug release. Foscarnet released from nanoparticles maintained the
      antiviral activity of the free drug when tested in vitro against lung fibroblasts
      (HELF) cells infected with HCMV strain AD-169. Moreover, nanoparticles showed no
      toxicity on non-infected HELF cells. These nanoparticles may represent a delivery
      system that could improve the therapeutic effect of foscarnet. 

PMID- 24742954
TI  - Tibiofemoral subchondral surface ratio (SSR) is a predictor of osteoarthritis
      symptoms and radiographic progression: data from the Osteoarthritis Initiative
      (OAI).
AB  - OBJECTIVE: Symptomatic knee osteoarthritis (OA) is poorly correlated with
      radiographic severity, but subchondral bone measures may be useful for risk
      assessment as bone shape is grossly unaffected at early radiographic stages. We
      sought to determine whether compartment-specific size mismatch in the naturally
      asymmetric tibiofemoral joint, measured as tibiofemoral subchondral surface ratio
      (SSR): (1) predicts incident symptoms, (2) predicts incident or progressive OA,
      (3) is reproducible and time invariant. DESIGN: OA Initiative participants with
      baseline MRIs and up to 48-month follow-up (n = 1,338) were analyzed. Logistic
      regression was used to determine the association between SSR and incident
      symptoms, incident OA, and progression of OA after adjusting for demographic,
      radiologic, injury-related, and lifestyle-related factors. Reproducibility was
      assessed as % coefficient of variation (CV) on repeat MRI studies at baseline and
      24 months. RESULTS: Increased medial SSR is protective against incident symptoms
      at 48 months (per 0.1 increase: OR 0.48 CI 0.30, 0.75; P = 0.001). Increased
      lateral SSR values are protective against lateral OA incidence (OR 0.23 CI 0.06,
      0.77; P = 0.016) or progression (OR 0.66 CI 0.43, 0.99; P = 0.049) at 24 months.
      Both medial and lateral SSR are stable over time (medial: mean change 0.001 SD
      0.016; lateral: mean change 0.000 SD 0.017) and are highly reproducible (3.0% CV
      medial SSR; 2.7% CV lateral SSR). CONCLUSIONS: A larger medial SSR is protective
      against developing OA-related symptoms. A larger lateral SSR is protective
      against lateral OA incidence or progression. Finally, lateral and medial SSR are
      stable over time and are highly reproducible across MRI studies.

PMID- 24742956
TI  - Response to Letter to the Editor entitled "Comments on 'OARSI guidelines for the
      non-surgical management of knee osteoarthritis'".

PMID- 24742955
TI  - The independent and combined effects of intensive weight loss and exercise
      training on bone mineral density in overweight and obese older adults with
      osteoarthritis.
AB  - OBJECTIVE: To determine the effects of dietary-induced weight loss (D) and weight
      loss plus exercise (D + E) compared to exercise alone (E) on bone mineral density
      (BMD) in older adults with knee osteoarthritis (OA). DESIGN: Data come from 284
      older (66.0 +/- 6.2 years), overweight/obese (body mass index (BMI) 33.4 +/- 3.7
      kg/m2), adults with knee OA enrolled in the Intensive Diet and Exercise for
      Arthritis (IDEA) study. Participants were randomized to 18 months of walking and
      strength training (E; n = 95), dietary-induced weight loss targeting 10% of
      baseline weight (D; n = 88) or a combination of the two (D + E; n = 101). Body
      weight and composition (DXA), regional BMD, were obtained at baseline and 18
      months. RESULTS: E, D, and D + E groups lost 1.3 +/- 4.5 kg, 9.1 +/- 8.6 kg and
      10.4 +/- 8.0 kg, respectively (P < 0.01). Significant treatment effects were
      observed for BMD in both hip and femoral neck regions, with the D and D + E
      groups showing similar relative losses compared to E (both P < 0.01). Despite
      reduced BMD, fewer overall participants had T-scores indicative of osteoporosis
      after intervention (9 at 18 months vs 10 at baseline). Within the D and D + E
      groups, changes in hip and femoral neck, but not spine, BMD correlated positively
      with changes in body weight (r = 0.21 and 0.54 respectively, both P <= 0.01).
      CONCLUSIONS: Weight loss via an intensive dietary intervention, with or without
      exercise, results in bone loss at the hip and femoral neck in overweight and
      obese, older adults with OA. Although the exercise intervention did not attenuate
      weight loss-associated reductions in BMD, classification of osteoporosis and
      osteopenia remained unchanged. CLINICAL TRIAL REGISTRATION NUMBER: NCT00381290.

PMID- 24742957
TI  - A novel approach for analyzing the behavior of industrial systems using weakest t
      norm and intuitionistic fuzzy set theory.
AB  - The present work investigates the various reliability parameters of industrial
      systems in terms of membership and non-membership functions by using alpha-cut
      and the weakest t-norm based arithmetic operations on triangular intuitionistic
      fuzzy sets. As the available information about the constituent components of the
      system is most of the time imprecise, incomplete, vague and conflicting, the
      management decisions are based on experience. Thus, the objective of this paper
      is to quantify the uncertainties that make the decisions realistic, generic and
      extensible for the application domain. Sensitivity of system performance has also
      been analyzed for showing the effect of taking wrong combinations of reliability
      parameters. The obtained results computed by the proposed approach are compared
      with the existing methodologies. The approach has been illustrated through a case
      study for supremacy. 

PMID- 24742958
TI  - Active disturbance rejection control: methodology and theoretical analysis.
AB  - The methodology of ADRC and the progress of its theoretical analysis are reviewed
      in the paper. Several breakthroughs for control of nonlinear uncertain systems,
      made possible by ADRC, are discussed. The key in employing ADRC, which is to
      accurately determine the "total disturbance" that affects the output of the
      system, is illuminated. The latest results in theoretical analysis of the ADRC
      based control systems are introduced. 

PMID- 24742959
TI  - Pumping iron to keep fit: modulation of siderophore secretion helps efficient
      aromatic utilization in Pseudomonas putida KT2440.
AB  - Studies of biotechnology applications of Pseudomonas putida KT2440 have been
      predominantly focused on regulation and expression of the toluene degradation
      (TOL) pathway. Unfortunately, there is limited information on the role of other
      physiological factors influencing aromatic utilization. In this report, we
      demonstrate that P. putida KT2440 increases its siderophore secretion in response
      to the availability of benzyl alcohol, a model aromatic substrate. It is argued
      that accelerated siderophore secretion in response to aromatic substrates
      provides an iron 'boost' which is required for the effective functioning of the
      iron-dependent oxygenases responsible for ring opening. Direct evidence for the
      cardinal role of siderophores in aromatic utilization is provided by evaluation
      of per capita siderophore secretion and comparative growth assessments of wild
      type and siderophore-negative mutant strains grown on an alternative carbon
      source. Accelerated siderophore secretion can be viewed as a compensatory
      mechanism in P. putida in the context of its inability to secrete more than one
      type of siderophore (pyoverdine) or to utilize heterologous siderophores.
      Stimulated siderophore secretion might be a key factor in successful integration
      and proliferation of this organism as a bio-augmentation agent for aromatic
      degradation. It not only facilitates efficient aromatic utilization, but also
      provides better opportunities for iron assimilation amongst diverse microbial
      communities, thereby ensuring better survival and proliferation. 

PMID- 24742960
TI  - A Na+-coupled C4-dicarboxylate transporter (Asuc_0304) and aerobic growth of
      Actinobacillus succinogenes on C4-dicarboxylates.
AB  - Actinobacillus succinogenes, which is known to produce large amounts of succinate
      during fermentation of hexoses, was able to grow on C4-dicarboxylates such as
      fumarate under aerobic and anaerobic conditions. Anaerobic growth on fumarate was
      stimulated by glycerol and the major product was succinate, indicating the
      involvement of fumarate respiration similar to succinate production from glucose.
      The aerobic growth on C4-dicarboxylates and the transport proteins involved were
      studied. Fumarate was oxidized to acetate. The genome of A. succinogenes encodes
      six proteins with similarity to secondary C4-dicarboxylate transporters,
      including transporters of the Dcu (C4-dicarboxylate uptake), DcuC (C4
      dicarboxylate uptake C), DASS (divalent anion : sodium symporter) and TDT
      (tellurite resistance dicarboxylate transporter) family. From the cloned genes,
      Asuc_0304 of the DASS family protein was able to restore aerobic growth on C4
      dicarboxylates in a C4-dicarboxylate-transport-negative Escherichia coli strain.
      The strain regained succinate or fumarate uptake, which was dependent on the
      electrochemical proton potential and the presence of Na(+). The transport had an
      optimum pH ~7, indicating transport of the dianionic C4-dicarboxylates. Transport
      competition experiments suggested substrate specificity for fumarate and
      succinate. The transport characteristics for C4-dicarboxylate uptake by cells of
      aerobically grown A. succinogenes were similar to those of Asuc_0304 expressed in
      E. coli, suggesting that Asuc_0304 has an important role in aerobic fumarate
      uptake in A. succinogenes. Asuc_0304 has sequence similarity to bacterial Na(+)
      dicarboxylate cotransporters and contains the carboxylate-binding signature.
      Asuc_0304 was named SdcA (sodium-coupled C4-dicarboxylate transporter from A.
      succinogenes). 

PMID- 24742961
TI  - Rifampicin suppresses thymineless death by blocking the transcription-dependent
      step of chromosome initiation.
AB  - Thymineless death (TLD), a phenomenon in which thymine auxotrophy becomes lethal
      when cells are starved of thymine, can be prevented by the presence of
      rifampicin, an RNA polymerase inhibitor. Several lines of evidence link TLD to
      chromosome initiation events. This suggests that rifampicin-mediated TLD
      suppression could be due to the inhibition of RNA synthesis required for DNA
      chromosomal initiation at oriC, although other mechanisms cannot be discarded. In
      this work, we show that the addition of different rifampicin concentrations to
      thymine-starved cells modulates TLD and chromosomal initiation capacity (ChIC).
      Time-lapse experiments find increasing levels of ChIC during thymine starvation
      correlated with the accumulation of simple-Y, double-Y and bubble arc replication
      intermediates at the oriC region as visualized by two-dimensional DNA agarose gel
      electrophoresis. None of these structures were observed following rifampicin
      addition or under genetic-physiological conditions that suppress TLD, indicating
      that abortive chromosome replication initiations under thymine starvation are
      crucial for this lethality. Significantly, the introduction of mioC and gid
      mutations which alter transcription levels around oriC, reduces ChIC and
      alleviates TLD. These results show that the impairment of transcription-dependent
      initiation caused by rifampicin addition, is responsible for TLD suppression. Our
      findings here may provide new avenues for the development of improved
      antibacterial treatments and chemotherapies based on thymine starvation-induced
      cell death.

PMID- 24742962
TI  - Novel mechanism of JNK pathway activation by adenoviral E1A.
AB  - The adenoviral oncoprotein E1A influences cellular regulation by interacting with
      a number of cellular proteins. In collaboration with complementary oncogenes, E1A
      fully transforms primary cells. As part of this action, E1A inhibits
      transcription of c-Jun:Fos target genes while promoting that of c-Jun:ATF2
      dependent genes including jun. Both c-Jun and ATF2 are hyperphosphorylated in
      response to E1A. In the current study, E1A was fused with the ligand binding
      domain of the estrogen receptor (E1A-ER) to monitor the immediate effect of E1A
      activation. With this approach we now show that E1A activates c-Jun N-terminal
      kinase (JNK), the upstream kinases MKK4 and MKK7, as well as the small GTPase
      Rac1. Activation of the JNK pathway requires the N-terminal domain of E1A, and,
      importantly, is independent of transcription. In addition, it requires the
      presence of ERM proteins. Downregulation of signaling components upstream of JNK
      inhibits E1A-dependent JNK/c-Jun activation. Taking these findings together, we
      show that E1A activates the JNK/c-Jun signaling pathway upstream of Rac1 in a
      transcription-independent manner, demonstrating a novel mechanism of E1A action. 

PMID- 24742963
TI  - Body temperature in early postpartum dairy cows.
AB  - A strategy widely adopted in the modern dairy industry is the introduction of
      postpartum health monitoring programs by trained farm personnel. Within these
      fresh cow protocols, various parameters (e.g., rectal temperature, attitude, milk
      production, uterine discharge, ketones) are evaluated during the first 5 to 14
      days in milk (DIMs) to diagnose relevant diseases. It is well documented that 14%
      to 66% of healthy cows exhibit at least one temperature of 39.5  degrees C or
      greater within the first 10 DIM. Although widely adopted, data on diagnostic
      performance of body temperature (BT) measurement to diagnose infectious diseases
      (e.g., metritis, mastitis) are lacking. Therefore, the objective of this study
      was to identify possible factors associated with BT in postpartum dairy cows. A
      study was conducted on a commercial dairy farm including 251 cows. In a total of
      217 cows, a vaginal temperature logger was inserted from DIM 2 to 10, whereas 34
      cows did not receive a temperature logger as control. Temperature loggers
      measured vaginal temperature every 10 minutes. Rectal temperature was measured
      twice daily in all cows. On DIM 2, 5, and 10, cows underwent a clinical
      examination. Body temperature was influenced by various parameters. Primiparous
      cows had 0.2  degrees C higher BT than multiparous cows. Multiparous cows that
      calved during June and July had higher BT than those that calved in May. In
      primiparous cows, this effect was only evident from DIM 7 to 10. Furthermore,
      abnormal calving conditions (i.e., assisted calving, dead calf, retained
      placenta, twins) affected BT in cows. This effect was more pronounced in
      multiparous cows. Abnormal vaginal discharge did increase BT in primiparous and
      multiparous cows. Primiparous cows suffering from hyperketonemia (beta
      hydroxybutyrat >= 1.4 mmol/L) had higher BT than those not affected. In
      multiparous cows, there was no association between hyperketonemia and BT. The
      results of this study clearly demonstrate that BT is influenced by various
      parameters in dairy cows. Therefore, these parameters have to be considered when
      interpreting measurements of BT in dairy cows. This information helps to explain
      the high incidence of type I and II errors when measuring BT and clearly
      illustrates that measures of BT should not be used as a single criterion to
      decide whether or not to provide antibiotic treatment to dairy cows. However,
      research-based test characteristics of other parameters (e.g., vaginal discharge)
      alone or in combination with BT are still lacking. 

PMID- 24742965
TI  - S-PC: an e-treatment application for management of smoke-quitting patients.
AB  - The main objective of this paper is to present a new program that facilitates the
      management of people who want to quit smoking, implemented through an e-treatment
      software called S-PC (Smoker Patient Control). S-PC is a web-based application
      that manages groups of patients, provides a bidirectional communication through
      mobile text messages and e-mails between patients and clinicians and offers
      advice and control to keep track of the patients and their status. A total of 229
      patients were enrolled in the study, randomly divided into two groups, although
      some variables were tested to ensure that there were no significant differences
      between the groups that could have an impact on the outcome of the treatment.
      There were no significant differences between the two groups regarding the
      ratio/number of males/females, tobacco dependence, co-oximetry, average cigarette
      consumption, current age and age when smoking started. The first group was made
      up of 104 patients (45.4% of the total) and followed a treatment that
      incorporated the S-PC tool, while the second one had 125 patients without the S
      PC tool. S-PC was evaluated for its effectiveness at assisting the patients to
      give up smoking, and its effect on clinician time management. 74% of the S-PC
      group completed the treatment without relapses and remained abstinent three
      months after the completion of the treatment, understanding abstinence as being
      continuous (with no relapses allowed and co-oximetry below 1 ppm) from the day of
      stopping. In contrast only 45.6% of the No S-PC group completed the treatment
      without relapses and remained abstinent three months after completion of the
      treatment. The rate of admittance to the program has doubled in one year and
      patients went from having to wait for 3 months to be immediately admitted into
      the program. This therapeutic e-health program aims at maximizing the number of
      patients that a professional can effectively help to quit smoking. In addition,
      the system also detects patients who are not progressing appropriately, allowing
      the professional to improve their treatment parameters dynamically.

PMID- 24742964
TI  - Induction of ovarian activity and ovulation in an induced ovulator, the maned
      wolf (Chrysocyon brachyurus), using GnRH agonist and recombinant LH.
AB  - Assisted reproductive techniques, such as ovarian manipulation and artificial
      insemination, are useful for enhancing genetic management of threatened wildlife
      maintained ex situ. In this study, we used noninvasive fecal hormone monitoring
      to investigate (1) the influence of pairing with a male on endocrine responses of
      female maned wolves (Chrysocyon brachyurus) to a GnRH agonist (deslorelin) and
      (2) the efficiency of recombinant LH (reLH) on ovulation induction in females
      housed alone. Deslorelin (2.1 mg Ovuplant) was given to females that were either
      paired with a male (n = 4) or housed alone (n = 7); the implant was removed 7 to
      11 days postimplantation. Three of seven singleton females were injected with
      reLH (0.0375 mg) on the day of implant removal, whereas the remaining females (n
      = 4) did not receive the additional treatment. Fecal samples were collected 5 to
      7 days/wk from all females starting 11 days prior to hormone insertion until at
      least 70 days post implant removal for a total of 11 hormone treatment cycles.
      Fecal estrogen and progestagen metabolites were extracted and analyzed by enzyme
      immunoassay. Evidence of ovulation, demonstrated by a surge of estrogen followed
      by a significant rise in progestagen, occurred in all paired females. Three of
      the four singleton females that did not receive reLH treatment exhibited no rise
      in progestagen after an estrogen surge. All singleton females treated with reLH
      exhibited a rise in fecal progestagen after injection, indicating ovulation. In
      conclusion, deslorelin is effective at inducing ovarian activity and ovulation in
      paired female maned wolves; however, exogenous reLH is needed to induce ovulation
      in females housed alone. The findings obtained from this study serve as a
      foundation for future application of artificial insemination to enhance genetic
      management of this threatened species ex situ. 

PMID- 24742966
TI  - Preparation of graphene oxide doped eggshell membrane bioplatform modified
      Prussian blue nanoparticles as a sensitive hydrogen peroxide sensor.
AB  - This study describes the preparation and characterization of graphene oxide doped
      eggshell membrane (GO-ESM) as a novel electrochemical bioplatform for
      electroanalytical purposes. The GO-ESM bioplatform was prepared by incorporation
      of GO nano-sheets into the ESM via a facile sonication procedure. Field emission
      scanning electron microscopy and X-ray diffraction powder techniques were used to
      characterize the developed bioplatform. The electrochemistry of GO-ESM was
      investigated by decorating it on the surface of carbon ceramic electrode (CCE) by
      an O-ring. The GO-ESM platform was modified with Prussian blue (PB) via a facile
      dip-coating method. Then the resulted modified electrode (PB|GO-ESM|CCE) was used
      as a novel hydrogen peroxide electrochemical sensor. The fabricated electrode
      responds efficiently to H2O2 over the concentration range 125nM-195MUM with a
      detection limit of 31nM (S/N=3) and sensitivity 8.8MUAMUM(-1)cm(-2). The PB|GO
      ESM|CCE has been successfully applied to determination of H2O2 content in spiked
      milk samples. Due to good stability, environmental friendly, cheapness, nontoxic,
      well behaved electrochemical properties, and biocompatibility, the fabricated
      bioplatform has the promising future for practical applications. 

PMID- 24742968
TI  - Stabilization of biothreat diagnostic samples through vitrification matrices.
AB  - Diagnostics for biothreat agents require sample shipment to reference labs for
      diagnosis of disease; however high/fluctuating temperatures during sample
      transport negatively affect sample quality and results. Vitrification additives
      preserve sample integrity for molecular-based assay diagnostics in the absence of
      refrigeration by imparting whole molecule stability to a plethora of
      environmental insults. Therefore, we have evaluated commercially available
      vitrification matrices' (Biomatrica's CloneStable(r) and RNAStable(r)) ability to
      stabilize samples of Yersinia pestis and Venezuelan Equine Encephalitis Virus.
      When heated to 95 degrees C in RNAStable(r), Y. pestis had a 13-fold improvement
      in detection via real-time PCR compared to heated samples in buffer. VEEV, in
      RNAStable(r) at 55 degrees C, had a ~10-fold improved detection versus heated
      samples in buffer. CloneStable(r) also preserved Y. pestis antigens for 7days
      after exposure to cycling temperatures. Overall, RNAStable(r) and CloneStable(r)
      respectively offered superior stabilization to nucleic acids and proteins in
      response to temperature fluctuations. 

PMID- 24742969
TI  - A simple plate-assay for screening extracellular naringinase produced by
      streptomycetes.
AB  - A simple plate-assay was developed with the purpose of detecting extracellular
      naringinase in streptomycetes. The naringin agar medium (NAM) was prepared by
      mixing carbon utilization medium (ISP9) and naringin. The clearing zones around
      colonies are correlated with the enzymatic activity. The assay validation was
      performed through the use of commercial naringinase (Penicillium decumbens). 

PMID- 24742967
TI  - Strigolactone analogues induce apoptosis through activation of p38 and the stress
      response pathway in cancer cell lines and in conditionally reprogrammed primary
      prostate cancer cells.
AB  - Strigolactones are a novel class of plant hormones produced in roots and regulate
      shoot and root development. We have previously shown that synthetic strigolactone
      analogues potently inhibit growth of breast cancer cells and breast cancer stem
      cells. Here we show that strigolactone analogues inhibit the growth and survival
      of an array of cancer-derived cell lines representing solid and non-solid cancer
      cells including: prostate, colon, lung, melanoma, osteosarcoma and leukemic cell
      lines, while normal cells were minimally affected. Treatment of cancer cells with
      strigolactone analogues was hallmarked by activation of the stress-related MAPKs:
      p38 and JNK and induction of stress-related genes; cell cycle arrest and
      apoptosis evident by increased percentages of cells in the sub-G1 fraction and
      Annexin V staining. In addition, we tested the response of patient-matched
      conditionally reprogrammed primary prostate normal and cancer cells. The tumor
      cells exhibited significantly higher sensitivity to the two most potent SL
      analogues with increased apoptosis confirmed by PARP1 cleavage compared to their
      normal counterpart cells. Thus, Strigolactone analogues are promising candidates
      for anticancer therapy by their ability to specifically induce cell cycle arrest,
      cellular stress and apoptosis in tumor cells with minimal effects on growth and
      survival of normal cells. 

PMID- 24742970
TI  - Aliskiren and losartan trial in non-diabetic chronic kidney disease.
AB  - INTRODUCTION: This is a report of a clinical trial on the therapeutic efficacy
      and safety of combined aliskiren and losartan (an angiotensin II receptor blocker
      (ARB)) versus aliskiren alone and ARB alone in non-diabetic chronic kidney
      disease (CKD) over a 3-year period. MATERIALS AND METHODS: This was a randomised
      trial in 155 patients with non-diabetic CKD comparing aliskiren (150 mg/day)
      (n=52) versus losartan (100 mg/day) (n=52) and the third group aliskiren (150
      mg/day) combined with losartan (100 mg/day) (n=51). The trial utilised primary
      renal end points of eGFR <15 ml/min or end-stage renal failure. RESULTS: All
      three groups had significant reduction of proteinuria (p<0.001 for all). The
      changes in eGFR, total urinary protein from baseline to each year were not
      significantly different between the three therapeutic groups. CONCLUSION: This
      study in non-diabetic CKD patients showed that combination therapy with aliskiren
      and ARB was as efficacious as aliskiren alone and ARB alone. There was one
      patient who developed a non-fatal stroke in the combined aliskiren and ARB group
      while the other two groups had none.

PMID- 24742971
TI  - Therapeutic strategies for treating osteolytic bone metastases.
AB  - The recent progress in oncologic management of patients with localized cancer or
      metastatic disease has permitted a significant improvement in life expectancy.
      Nevertheless, bone metastases and their consequent skeletal-related events (SREs)
      are still associated with unfavorable prognosis and greatly affect quality of
      life. Global management of these bone metastases includes traditional local
      approaches (surgery, radiotherapy, etc.) and systemic administration of
      chemotherapeutic agents. This review focuses on treatments specific for bone
      metastases and, in particular, on inhibitors of bone resorption that are
      effective for preventing and delaying the development of SREs. 

PMID- 24742972
TI  - Forehead reflectance photoplethysmography to monitor heart rate: preliminary
      results from neonatal patients.
AB  - Around 5%-10% of newborn babies require some form of resuscitation at birth and
      heart rate (HR) is the best guide of efficacy. We report the development and
      first trial of a device that continuously monitors neonatal HR, with a view to
      deployment in the delivery room to guide newborn resuscitation. The device uses
      forehead reflectance photoplethysmography (PPG) with modulated light and lock-in
      detection. Forehead fixation has numerous advantages including ease of sensor
      placement, whilst perfusion at the forehead is better maintained in comparison to
      the extremities. Green light (525 nm) was used, in preference to the more usual
      red or infrared wavelengths, to optimize the amplitude of the pulsatile signal.
      Experimental results are presented showing simultaneous PPG and electrocardiogram
      (ECG) HRs from babies (n = 77), gestational age 26-42 weeks, on a neonatal
      intensive care unit. In babies ?32 weeks gestation, the median reliability was
      97.7% at +/-10 bpm and the limits of agreement (LOA) between PPG and ECG were
      +8.39 bpm and -8.39 bpm. In babies <32 weeks gestation, the median reliability
      was 94.8% at +/-10 bpm and the LOA were +11.53 bpm and -12.01 bpm. Clinical
      evaluation during newborn deliveries is now underway. 

PMID- 24742973
TI  - Toehold-mediated strand displacement reaction triggered isothermal DNA
      amplification for highly sensitive and selective fluorescent detection of single
      base mutation.
AB  - Highly sensitive and selective detection strategy for single-base mutations is
      essential for risk assessment of malignancy and disease prognosis. In this work,
      a fluorescent detection method for single-base mutation was proposed based on
      high selectivity of toehold-mediated strand displacement reaction (TSDR) and
      powerful signal amplification capability of isothermal DNA amplification. A
      discrimination probe was specially designed with a stem-loop structure and an
      overhanging toehold domain. Hybridization between the toehold domain and the
      perfect matched target initiated the TSDR along with the unfolding of the
      discrimination probe. Subsequently, the target sequence acted as a primer to
      initiate the polymerization and nicking reactions, which released a great
      abundant of short sequences. Finally, the released strands were annealed with the
      reporter probe, launching another polymerization and nicking reaction to produce
      lots of G-quadruplex DNA, which could bind the N-methyl mesoporphyrin IX to yield
      an enhanced fluorescence response. However, when there was even a single base
      mismatch in the target DNA, the TSDR was suppressed and so subsequent isothermal
      DNA amplification and fluorescence response process could not occur. The proposed
      approach has been successfully implemented for the identification of the single
      base mutant sequences in the human KRAS gene with a detection limit of 1.8 pM.
      Furthermore, a recovery of 90% was obtained when detecting the target sequence in
      spiked HeLa cells lysate, demonstrating the feasibility of this detection
      strategy for single-base mutations in biological samples.

PMID- 24742974
TI  - eGFP-pHsens as a highly sensitive fluorophore for cellular pH determination by
      fluorescence lifetime imaging microscopy (FLIM).
AB  - The determination of pH in the cell cytoplasm or in intracellular organelles is
      of high relevance in cell biology. Also in plant cells, organelle-specific pH
      monitoring with high spatial precision is an important issue, since e.g. DeltapH
      across thylakoid membranes is the driving force for ATP synthesis critically
      regulating photoprotective mechanisms like non-photochemical quenching (NPQ) of
      chlorophyll (Chl) fluorescence or the xanthophyll cycle. In animal cells, pH
      determination can serve to monitor proton permeation across membranes and,
      therefore, to assay the efficiency of drugs against proton-selective transporters
      or ion channels. In this work, we demonstrate the applicability of the pH
      sensitive GFP derivative (eGFP-pHsens, originally termed deGFP4 by Hanson et al.
      [1]) for pH measurements using fluorescence lifetime imaging microscopy (FLIM)
      with excellent precision. eGFP-pHsens was either expressed in the cytoplasm or
      targeted to the mitochondria of Chinese hamster ovary (CHO-K1) cells and applied
      here for monitoring activity of the M2 proton channel from influenza A virus. It
      is shown that the M2 protein confers high proton permeability of the plasma
      membrane upon expression in CHO-K1 cells resulting in rapid and strong changes of
      the intracellular pH upon pH changes of the extracellular medium. These pH
      changes are abolished in the presence of amantadine, a specific blocker of the M2
      proton channel. These results were obtained using a novel multi-parameter FLIM
      setup that permits the simultaneous imaging of the fluorescence amplitude ratios
      and lifetimes of eGFP-pHsens enabling the quick and accurate pH determination
      with spatial resolution of 500 nm in two color channels with time resolution of
      below 100 ps. With FLIM, we also demonstrate the simultaneous determination of pH
      in the cytoplasm and mitochondria showing that the pH in the mitochondrial matrix
      is slightly higher (around 7.8) than that in the cytoplasm (about 7.0). The
      results obtained for CHO-K1 cells without M2 channels in comparison to M2
      expressing cells show that the pH dynamics is determined by the specific H+
      permeability of the membrane, the buffering of protons in the internal cell lumen
      and/or an outwardly directed proton pump activity that stabilizes the interior pH
      at a higher level than the external acidic pH. This article is part of a special
      issue entitled: photosynthesis research for sustainability: keys to produce clean
      energy.

PMID- 24742975
TI  - Chronic kidney disease as a risk factor for acute community-acquired infections
      in high-income countries: a systematic review.
AB  - OBJECTIVE: A systematic review of the association of predialysis chronic kidney
      disease (CKD) with the incidence of acute, community-acquired infections. DESIGN:
      We searched the MEDLINE, EMBASE and Cochrane databases (inception to 16 January
      2014) for studies analysing the association of predialysis kidney disease with
      the incidence of acute, community-acquired urinary tract infection (UTI), lower
      respiratory tract or central nervous system infections or sepsis. Studies were
      required to include at least 30 participants with and without kidney disease.
      SETTING AND PARTICIPANTS: Community-based populations of adults in high-income
      countries. OUTCOME MEASURES: Acute, community-acquired UTI, lower respiratory
      tract or central nervous system infections or sepsis. RESULTS: We identified 14
      eligible studies. Estimates from two studies lacked 95% CIs and SEs. The
      remaining 12 studies yielded 17 independent effect estimates. Only three studies
      included infections managed in the community. Quality assessment revealed that
      probable misclassification of kidney disease status and poor adjustment for
      confounding were common. There was evidence from a few large high-quality studies
      of a graded association between predialysis CKD stage and hospitalisation for
      infection. One study found an interaction with age, with a declining effect of
      CKD on infection risk as age increased. There was evidence of between-studies
      heterogeneity (I(2)=96.5%, p<0.001) which persisted in subgroup analysis, and
      thus meta-analysis was not performed. CONCLUSIONS: Predialysis kidney disease
      appears to be associated with increased risk of severe infection. Whether
      predialysis kidney disease increases the susceptibility to infections and whether
      age modifies this association remains unclear.

PMID- 24742976
TI  - Youth tobacco access: trends and policy implications.
AB  - OBJECTIVE: We examined whether the supply routes via which New Zealand
      adolescents aged 14-15 years accessed tobacco had changed during a period of
      dynamic policy activity. SETTING: We analysed data from seven consecutive years
      (2006-2012) of the New Zealand Action on Smoking and Health (ASH) Year 10 survey,
      a nationwide cross-sectional annual survey. PARTICIPANTS: All New Zealand schools
      teaching Year 10 students are invited to participate in the survey; school-level
      participation rates have ranged between 44% and 58% and more than 25 000 students
      have responded to the survey in each year. The results presented draw on the
      subsample who reported smoking when surveyed (N~9200). The data were weighted by
      age, ethnicity and school socioeconomic status (SES) to remove effects of
      systematic over-response by New Zealand Europeans and under-response by those in
      lower SES groups from trend analyses. PRIMARY AND SECONDARY OUTCOME MEASURES: The
      survey measured adolescents' main reported tobacco supply source. RESULTS:
      Smoking prevalence declined significantly (8.1%) over the period examined (linear
      tend coefficient: -0.74; 95% CI -1.03 to -0.45, significant p<0.01). Friends
      showed a significant decline in relative importance as a supply source while
      caregivers and other sources showed a significant increase over the period
      examined. CONCLUSIONS: The findings show that social supply, particularly via
      friends, caregivers and others, such as older siblings, is a key tobacco source
      for adolescents; commercial supply is much less important. The findings raise
      questions about the additional measures needed to reduce smoking among youth.
      Endgame policies that make tobacco more difficult to obtain and less appealing
      and convenient to gift merit further investigation.

PMID- 24742977
TI  - Effect of green tea supplementation on blood pressure among overweight and obese
      adults: a protocol for a systematic review.
AB  - INTRODUCTION: Emerging randomised controlled trials (RCTs) exploring the effect
      of green tea (GT) supplementation or GT extract (GTE) on blood pressure (BP)
      among overweight and obese adults yielded inconclusive results. We aim to conduct
      a systematic review to summarise the evidence of RCTs until now, to clarify the
      efficacy of GT supplementation or GTE in BP in overweight and obese populations.
      METHODS AND ANALYSIS: The Cochrane Central Register of Controlled Trials,
      MEDLINE, EMBASE and ClinicalTrials.gov will be searched to retrieve potential
      RCTs. Unpublished studies will be identified by searching the abstract books or
      websites of the three major conference proceedings: the International Society of
      Hypertension, the Nutrition & Health Conference and the World Congress of
      Nutrition and Health. A random-effects meta-analysis will be performed to pool
      the mean difference for the change in BP from baseline (ie, postintervention BP
      minus baseline BP) between intervention groups and placebo groups of the included
      studies, presenting the pooled results with 95% CIs. Subgroups analyses will be
      conducted according to different doses of GT or GTE, trial duration, geographic
      regions, overweight versus obese participants, and participants with versus
      without change in body weight after intervention. Sensitivity analysis will be
      performed by excluding studies classified as having a high risk of bias, applying
      a fixed-effects model, using the postintervention BP for analyses and excluding
      trials with non-study cointerventions. ETHICS AND DISSEMINATION: This systematic
      review will be published in a peer-reviewed journal. It will be disseminated
      electronically and in print. Summarising the RCT evidence to clarify the efficacy
      in BP among overweight and obese adults will aid in making the dietary
      recommendation of GT and improving the clinical management of hypertension. TRIAL
      REGISTRATION NUMBER: PROSPERO CRD42014007273.

PMID- 24742978
TI  - A randomised controlled trial of an intervention to facilitate the implementation
      of healthy eating and physical activity policies and practices in childcare
      services.
AB  - INTRODUCTION: Childhood overweight and obesity tracks into adulthood, increasing
      the risk of developing future chronic disease. Implementing initiatives promoting
      healthy eating and physical activity in childcare settings has been identified as
      a priority to prevent excessive child weight gain. Despite this, few trials have
      been conducted to assess the effectiveness of interventions to support population
      wide implementation of such initiatives. The aim of this study is to assess the
      effectiveness of a multicomponent intervention in increasing the implementation
      of healthy eating and physical activity policies and practices by centre-based
      childcare services. METHODS AND ANALYSIS: The study will employ a parallel group
      randomised controlled trial design. A sample of 128 childcare services in the
      Hunter region of New South Wales, Australia, will be recruited to participate in
      the trial. 64 services will be randomly allocated to a 12-month implementation
      intervention. The remaining 64 services will be allocated to a usual care control
      group. The intervention will consist of a number of strategies to facilitate
      childcare service implementation of healthy eating and physical activity policies
      and practices. Intervention strategies will include implementation support staff,
      securing executive support, consensus processes, staff training, academic
      detailing visits, performance monitoring and feedback, tools and resources, and a
      communications strategy. The primary outcome of the trial will be the prevalence
      of services implementing all healthy eating and physical activity policies and
      practices targeted by the intervention. To assess the effectiveness of the
      intervention, telephone surveys with nominated supervisors and room leaders of
      childcare services will be conducted at baseline and immediately
      postintervention. ETHICS AND DISSEMINATION: The study was approved by the Hunter
      New England Human Research Ethics Committee and the University of Newcastle Human
      Research Ethics Committee. Study findings will be disseminated widely through
      peer-reviewed publications and conference presentations. TRIAL REGISTRATION
      NUMBER: Australian Clinical Trials Registry ACTRN12612000927820.

PMID- 24742979
TI  - Patient preferences and acceptable risk for computed tomography in trauma.
AB  - BACKGROUND: Rising use of computed tomography (CT) to evaluate patients with
      trauma has increased both patient costs and risk of cancer from ionizing
      radiation, without demonstrable improvements in outcome. Patient-centred care
      mandates disclosure of the potential risks, costs and benefits of diagnostic
      testing whenever possible. OBJECTIVE: We sought to determine (1) patient
      preferences regarding emergency department (ED) real-time discussions of risks
      and costs of CT during their trauma evaluations; and (2) whether varying levels
      of odds of detection of life-threatening injury (LTI) were associated with
      changes in patient preferences for CT. METHODS: Excluding patients already
      receiving CT and patients with altered mental status, we surveyed adult, English
      speaking patients at four Level I verified trauma centres. After informing
      subjects of cancer risks associated with chest CT, we used hypothetical scenarios
      with varying LTIs to assess patients' preferences regarding CT. RESULTS: Of 941
      patients enrolled, 50% were male and their mean age was 42 years. Most patients
      stated they would prefer to discuss CT radiation risks (73.5%, 95% CI [66.1
      80.8]) and costs (53.2%, 95% CI [46.1-60.4]) with physicians. As the odds of
      detecting LTI decreased, preferences for receiving CT decreased accordingly: LTI
      25% (desire 91.2%, 95% CI [89.4-93.1]), LTI 10% (desire 79.3%, 95% CI [76.7
      81.9]), LTI 5% (desire 69.1%, 95% CI [66.1-72.1]) and LTI <2% (desire 53.8%, 95%
      CI [50.6-57.0]). If the LTI was <2% and subjects were required to pay $1000 out
      of-pocket, only 34.5% (95% CI 31.4-37.5) would opt for CT. CONCLUSION: Most non
      critically injured patients prefer to discuss radiation risks and costs of CT
      prior to receiving imaging. As the odds of detecting LTI decrease, fewer patients
      prefer to have CT; at an LTI threshold of 2%, approximately half of patients
      would prefer to forego CT. Adding out-of-pocket costs reduced this proportion to
      one-third of patients.

PMID- 24742980
TI  - WITHDRAWN: Riluzole alleviates early neutrophil infiltration, brain oedema and
      lipid peroxidation in the traumatic brain tissue but does not induce
      neurotoxicity in non-traumatic brain tissue in rats.
AB  - This article has been withdrawn at the request of the editor since, in breach of
      ethical guidelines and journal policies, the manuscript was submitted without the
      full knowledge and consent of all authors listed. 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- 24742981
TI  - Biohydrogen, biomethane and bioelectricity as crucial components of biorefinery
      of organic wastes: a review.
AB  - Biohydrogen is a sustainable form of energy as it can be produced from organic
      waste through fermentation processes involving dark fermentation and
      photofermentation. Very often biohydrogen is included as a part of biorefinery
      approaches, which reclaim organic wastes that are abundant sources of renewable
      and low cost substrate that can be efficiently fermented by microorganisms. The
      aim of this work was to critically assess selected bioenergy alternatives from
      organic solid waste, such as biohydrogen and bioelectricity, to evaluate their
      relative advantages and disadvantages in the context of biorefineries, and
      finally to indicate the trends for future research and development. Biorefining
      is the sustainable processing of biomass into a spectrum of marketable products,
      which means: energy, materials, chemicals, food and feed. Dark fermentation of
      organic wastes could be the beach-head of complete biorefineries that generate
      biohydrogen as a first step and could significantly influence the future of solid
      waste management. Series systems show a better efficiency than one-stage process
      regarding substrate conversion to hydrogen and bioenergy. The dark fermentation
      also produces fermented by-products (fatty acids and solvents), so there is an
      opportunity for further combining with other processes that yield more bioenergy.
      Photoheterotrophic fermentation is one of them: photosynthetic heterotrophs, such
      as non-sulfur purple bacteria, can thrive on the simple organic substances
      produced in dark fermentation and light, to give more H2. Effluents from
      photoheterotrophic fermentation and digestates can be processed in microbial fuel
      cells for bioelectricity production and methanogenic digestion for methane
      generation, thus integrating a diverse block of bioenergies. Several digestates
      from bioenergies could be used for bioproducts generation, such as cellulolytic
      enzymes and saccharification processes, leading to ethanol fermentation (another
      bioenergy), thus completing the inverse cascade. Finally, biohydrogen, biomethane
      and bioelectricity could contribute to significant improvements for solid organic
      waste management in agricultural regions, as well as in urban areas. 

PMID- 24742982
TI  - Minoxidil may suppress androgen receptor-related functions.
AB  - Although minoxidil has been used for more than two decades to treat androgenetic
      alopecia (AGA), an androgen-androgen receptor (AR) pathway-dominant disease, its
      precise mechanism of action remains elusive. We hypothesized that minoxidil may
      influence the AR or its downstream signaling. These tests revealed that minoxidil
      suppressed AR-related functions, decreasing AR transcriptional activity in
      reporter assays, reducing expression of AR targets at the protein level, and
      suppressing AR-positive LNCaP cell growth. Dissecting the underlying mechanisms,
      we found that minoxidil interfered with AR-peptide, AR-coregulator, and AR N/C
      terminal interactions, as well as AR protein stability. Furthermore, a
      crystallographic analysis using the AR ligand-binding domain (LBD) revealed
      direct binding of minoxidil to the AR in a minoxidil-AR-LBD co-crystal model, and
      surface plasmon resonance assays demonstrated that minoxidil directly bound the
      AR with a K(d) value of 2.6 uM. Minoxidil also suppressed AR-responsive reporter
      activity and decreased AR protein stability in human hair dermal papilla cells.
      The current findings provide evidence that minoxidil could be used to treat both
      cancer and age-related disease, and open a new avenue for applications of
      minoxidil in treating androgen-AR pathway-related diseases.

PMID- 24742983
TI  - Interaction between sulthiame and clobazam: sulthiame inhibits the metabolism of
      clobazam, possibly via an action on CYP2C19.
AB  - The aim of this study was to investigate the effect of sulthiame (STM) on the
      pharmacokinetics of clobazam (CLB) by determining the concentration to dose (CD)
      ratio (serum level (ng/ml) divided by dose (mg/kg)) of CLB and that of N
      desmethyl-clobazam (DMCLB). We evaluated five patients (an adult and four
      children) whose serum CLB and DMCLB concentrations were monitored after the
      addition or discontinuation of STM. Four of the five patients were CYP2C19
      intermediate metabolizers, and one patient was an extensive metabolizer. When the
      patients were taking STM (100-275 mg/day), the mean CD ratio of DMCLB increased
      by 82.6 to 248.5%, which was higher than when they were not using STM. The
      increase was dose-dependent. In contrast, the CD ratio of CLB remained stable
      after addition or discontinuation of STM. These data suggest that STM has the
      potential to inhibit CYP2C19 enzyme activity. During combination therapy with STM
      and CLB in patients with CYP2C19 intermediate or extensive metabolizer
      phenotypes, monitoring of DMCLB concentrations may be helpful in ascertaining CLB
      related adverse effects.

PMID- 24742984
TI  - Aging-associated oxidative stress leads to decrease in IAS tone via RhoA/ROCK
      downregulation.
AB  - Internal anal sphincter (IAS) tone plays an important role in rectoanal
      incontinence (RI). IAS tone may be compromised during aging, leading to RI in
      certain patients. We examined the influence of oxidative stress in the aging
      associated decrease in IAS tone (AADI). Using adult (4-6 mo old) and aging (24-30
      mo old) rats, we determined the effect of oxidative stress on IAS tone and the
      regulatory RhoA/ROCK signal transduction cascade. We determined the effect of the
      oxidative stress inducer LY83583, which produces superoxide anions (O2 (.-)), on
      basal and stimulated IAS tone before and after treatment of intact smooth muscle
      strips and smooth muscle cells with the O2 (.-) scavenger SOD. Our data showed
      that AADI was associated with a decrease in RhoA/ROCK expression at the
      transcriptional and translational levels. Oxidative stress with a LY83583
      mediated decrease in IAS tone and relaxation of IAS smooth muscle cells was
      associated with a decrease in RhoA/ROCK signal transduction, which was reversible
      by SOD. In addition, LY83583 caused a significant decrease in IAS contraction
      produced by the RhoA activator and a known RhoA/ROCK agonist, U46619, that was
      also reversible by SOD. The inhibitory effects of LY83583 and the ROCK inhibitor
      Y27632 on the U46619-induced increase in IAS tone were similar. We conclude that
      an increase in oxidative stress plays an important role in AADI in the elderly
      and may be one of the underlying mechanisms of RI in certain aging patients. 

PMID- 24742985
TI  - Effect of pancreatic polypeptide on gastric accommodation and gastric emptying in
      conscious rats.
AB  - Pancreatic polypeptide (PP) is an anorexigenic hormone released from pancreatic F
      cells upon food intake. We aimed to determine the effect of PP on gastric
      accommodation and gastric emptying in conscious Wistar HAN rats to investigate
      whether effects on motor function could contribute to its anorexigenic effects.
      Intragastric pressure (IGP) was measured through a chronically implanted gastric
      fistula during the infusion of a nutrient meal (Nutridrink; 0.5 ml/min). Rats
      were treated with PP (0, 33 and 100 pmol.kg(-1).min(-1)) in combination with N(G)
      nitro-L-arginine methyl ester (L-NAME; 180 mg.kg(-1).h(-1)), atropine (3 mg.kg(
      1).h(-1)), or vehicle. Furthermore, the effect of PP was tested after
      subdiaphragmal vagotomy of the stomach. Gastric emptying of a noncaloric and a
      caloric meal after treatment with 100 pmol.kg(-1).min(-1) PP or vehicle was
      compared using X-rays. PP significantly increased IGP during nutrient infusion
      compared with vehicle (P < 0.01). L-NAME and atropine significantly increased IGP
      during nutrient infusion compared with vehicle treatment (P < 0.005 and 0.01,
      respectively). The effect of PP on IGP during nutrient infusion was abolished in
      the presence of L-NAME and in the presence of atropine. In vagotomized rats, PP
      increased IGP compared with intact controls (P < 0.05). PP significantly delayed
      gastric emptying of both a noncaloric (P < 0.05) and a caloric (P < 0.005) meal.
      PP inhibits gastric accommodation and delays gastric emptying, probably through
      inhibition of nitric oxide release. These results indicate that, besides the well
      known centrally mediated effects, PP might decrease food intake through
      peripheral mechanisms.

PMID- 24742986
TI  - Acute murine colitis reduces colonic 5-aminosalicylic acid metabolism by
      regulation of N-acetyltransferase-2.
AB  - Pharmacotherapy based on 5-aminosalicylic acid (5-ASA) is a preferred treatment
      for ulcerative colitis, but variable patient response to this therapy is
      observed. Inflammation can affect therapeutic outcomes by regulating the
      expression and activity of drug-metabolizing enzymes; its effect on 5-ASA
      metabolism by the colonic arylamine N-acetyltransferase (NAT) enzyme isoforms is
      not firmly established. We examined if inflammation affects the capacity for
      colonic 5-ASA metabolism and NAT enzyme expression. 5-ASA metabolism by colonic
      mucosal homogenates was directly measured with a novel fluorimetric rate assay. 5
      ASA metabolism reported by the assay was dependent on Ac-CoA, inhibited by
      alternative NAT substrates (isoniazid, p-aminobenzoylglutamate), and saturable
      with Km (5-ASA) = 5.8 MUM. A mouse model of acute dextran sulfate sodium (DSS)
      colitis caused pronounced inflammation in central and distal colon, and modest
      inflammation of proximal colon, defined by myeloperoxidase activity and
      histology. DSS colitis reduced capacity for 5-ASA metabolism in central and
      distal colon segments by 52 and 51%, respectively. Use of selective substrates of
      NAT isoforms to inhibit 5-ASA metabolism suggested that mNAT2 mediated 5-ASA
      metabolism in normal and colitis conditions. Western blot and real-time RT-PCR
      identified that proximal and distal mucosa had a decreased mNAT2 protein-to-mRNA
      ratio after DSS. In conclusion, an acute colonic inflammation impairs the
      expression and function of mNAT2 enzyme, thereby diminishing the capacity for 5
      ASA metabolism by colonic mucosa. 

PMID- 24742987
TI  - Lactobacillus rhamnosus HN001 decreases the severity of necrotizing enterocolitis
      in neonatal mice and preterm piglets: evidence in mice for a role of TLR9.
AB  - Necrotizing enterocolitis (NEC) is the leading cause of death from
      gastrointestinal disease in premature infants and develops partly from an
      exaggerated intestinal epithelial immune response to indigenous microbes. There
      has been interest in administering probiotic bacteria to reduce NEC severity, yet
      concerns exist regarding infection risk. Mechanisms of probiotic activity in NEC
      are unknown although activation of the microbial DNA receptor Toll-like receptor
      9 (TLR9) has been postulated. We now hypothesize that the Gram-positive bacterium
      Lactobacillus rhamnosus HN001 can attenuate NEC in small and large animal models,
      that its microbial DNA is sufficient for its protective effects, and that
      protection requires activation of the Toll-like receptor 9 (TLR9). We now show
      that oral administration of live or UV-inactivated Lactobacillus rhamnosus HN001
      attenuates NEC severity in newborn mice and premature piglets, as manifest by
      reduced histology score, attenuation of mucosal cytokine response, and improved
      gross morphology. TLR9 was required for Lactobacillus rhamnosus-mediated
      protection against NEC in mice, as the selective decrease of TLR9 from the
      intestinal epithelium reversed its protective effects. Strikingly, DNA of
      Lactobacillus rhamnosus HN001 reduced the extent of proinflammatory signaling in
      cultured enterocytes and in samples of resected human ileum ex vivo, suggesting
      the therapeutic potential of this probiotic in clinical NEC. Taken together,
      these findings illustrate that Lactobacillus rhamnosus HN001 is an effective
      probiotic for NEC via activation of the innate immune receptor TLR9 and that
      Lactobacillus rhamnosus DNA is sufficient for its protective effects, potentially
      reducing concerns regarding the infectious risk of this novel therapeutic
      approach. 

PMID- 24742988
TI  - Pharmacological ceramide reduction alleviates alcohol-induced steatosis and
      hepatomegaly in adiponectin knockout mice.
AB  - Hepatosteatosis, the ectopic accumulation of lipid in the liver, is one of the
      earliest clinical signs of alcoholic liver disease (ALD). Alcohol-dependent
      deregulation of liver ceramide levels as well as inhibition of AMP-activated
      protein kinase (AMPK) and peroxisome proliferator-activated receptor alpha (PPAR
      alpha) activity are thought to contribute to hepatosteatosis development.
      Adiponectin can regulate lipid handling in the liver and has been shown to reduce
      ceramide levels and activate AMPK and PPAR-alpha. However, the mechanisms by
      which adiponectin prevents alcoholic hepatosteatosis remain incompletely
      characterized. To address this question, we assessed ALD progression in wild-type
      (WT) and adiponectin knockout (KO) mice fed an ethanol-containing liquid diet or
      isocaloric control diet. Adiponectin KO mice relative to WT had increased alcohol
      induced hepatosteatosis and hepatomegaly, similar modest increases in serum
      alanine aminotransferase, and reduced liver TNF. Restoring circulating
      adiponectin levels using recombinant adiponectin ameliorated alcohol-induced
      hepatosteatosis and hepatomegaly in adiponectin KO mice. Alcohol-fed WT and
      adiponectin KO animals had equivalent reductions in AMPK protein and PPAR-alpha
      DNA binding activity compared with control-fed animals. No difference in P
      AMPK/AMPK ratio was detected, suggesting that alcohol-dependent deregulation of
      AMPK and PPAR-alpha in the absence of adiponectin are not primary causes of the
      observed increase in hepatosteatosis in these animals. By contrast, alcohol
      treatment increased liver ceramide levels in adiponectin KO but not WT mice.
      Importantly, pharmacological inhibition of de novo ceramide synthesis in
      adiponectin KO mice abrogated alcohol-mediated increases in liver ceramides,
      steatosis, and hepatomegaly. These data suggest that adiponectin reduces alcohol
      induced steatosis and hepatomegaly through regulation of liver ceramides, but its
      absence does not exacerbate alcohol-induced liver damage. 

PMID- 24742989
TI  - Ron receptor signaling is protective against DSS-induced colitis in mice.
AB  - Inflammatory bowel diseases (IBD) are chronic inflammatory disorders of the
      intestine that result in painful and debilitating complications. Currently no
      cure exists for IBD, and treatments are primarily aimed at reducing inflammation
      to alleviate symptoms. Genome-wide linkage studies have identified the Ron
      receptor tyrosine kinase (TK) and its ligand, hepatocyte growth factor-like
      protein (HGFL), as genes highly associated with IBD. However, only scant
      information exists on the role of Ron or HGFL in IBD. Based on the linkage of Ron
      to IBD, we directly examined the biological role of Ron in colitis. Wild-type
      mice and mice lacking the TK signaling domain of Ron (TK-/- mice) were utilized
      in a well-characterized model of chronic colitis induced by cyclic exposure to
      dextran sulfate sodium. In this model, TK-/- mice were more susceptible to injury
      as judged by increased mortality compared with control mice and developed more
      severe colitis. Loss of Ron led to significantly reduced body weights and more
      aggressive clinical and histopathologies. Ron loss also resulted in a dramatic
      reduction in colonic epithelial cell proliferation and increased proinflammatory
      cytokine production, which was associated with alterations in important signaling
      pathways known to regulate IBD. Examination of human gene expression data further
      supports the contention that loss of Ron signaling is associated with IBD. In
      total, our studies point to important functional roles for Ron in IBD by
      regulating healing of the colonic epithelium and by controlling cytokine
      secretion.

PMID- 24742990
TI  - Differential eosinophil and mast cell regulation: mast cell viability and
      accumulation in inflammatory tissue are independent of proton-sensing receptor
      GPR65.
AB  - Extracellular acidification has been observed in allergic inflammatory diseases.
      Recently, we demonstrated that the proton-sensing receptor G protein-coupled
      receptor 65 (GPR65) regulates eosinophil survival in an acidic environment in
      vitro and eosinophil accumulation in an allergic lung inflammation model. For
      mast cells, another inflammatory cell type critical for allergic responses, it
      remains unknown whether GPR65 is expressed and/or regulates mast cell viability.
      Thus, in the present study, we employed in vitro experiments and an intestinal
      anaphylaxis model in which both mastocytosis and eosinophilia can be observed,
      particularly in the gastrointestinal tract, to enable us to directly compare the
      effect of GPR65 expression on these two cell types. We identified GPR65
      expression on mast cells; however, unlike eosinophil viability, mast cell
      viability in vitro is not affected by acidification or GPR65 expression.
      Mechanistically, we determined that mast cells do not respond to extracellular
      acidification with increased cAMP levels. Furthermore, in the intestinal
      anaphylaxis model, we observed a significant reduction of eosinophils (59.1 +/-
      9.2% decrease) in the jejunum of allergen-challenged GPR65-deficient mice
      compared with allergen-challenged wild-type mice, despite the degree of antigen
      sensitization and the expression levels of Th2 cytokines (Il4, Il13) and
      eosinophil chemokines (Ccl11, Ccl24) in the jejunum being comparable. In
      contrast, the accumulation of mast cells in allergen-challenged mice was not
      affected by GPR65 deficiency. In conclusion, our study demonstrates differential
      regulation of eosinophils and mast cells in inflammatory tissue, with mast cell
      viability and accumulation being independent of GPR65. 

PMID- 24742991
TI  - Disruption of epithelial barrier by quorum-sensing N-3-(oxododecanoyl)-homoserine
      lactone is mediated by matrix metalloproteinases.
AB  - The intestinal epithelium forms a selective barrier maintained by tight junctions
      (TJs) and separating the luminal environment from the submucosal tissues. N
      acylhomoserine lactone (AHL) quorum-sensing molecules produced by gram-negative
      bacteria in the gut can influence homeostasis of the host intestinal epithelium.
      In the present study, we evaluated the regulatory mechanisms affecting the impact
      of two representative long- and short-chain AHLs, N-3-(oxododecanoyl)-homoserine
      lactone (C12-HSL) and N-butyryl homoserine lactone (C4-HSL), on barrier function
      of human intestinal epithelial Caco-2 cells. Treatment with C12-HSL, but not with
      C4-HSL, perturbed Caco-2 barrier function; the effect was associated with
      decreased levels of the TJ proteins occludin and tricellulin and their
      delocalization from the TJs. C12-HSL also induced matrix metalloprotease (MMP)-2
      and MMP-3 activation via lipid raft- and protease-activated receptor (PAR)
      dependent signaling. Pretreatment with lipid raft disruptors, PAR antagonists, or
      MMP inhibitors restored the C12-HSL-induced loss of the TJ proteins and increased
      permeability of Caco-2 cell monolayers. These results indicate that PAR/lipid
      raft-dependent MMP-2 and -3 activation followed by degradation of occludin and
      tricellulin are involved in C12-HSL-induced alterations of epithelial
      paracellular barrier functions. 

PMID- 24742992
TI  - Disruption of retinoblastoma protein expression in the intestinal epithelium
      impairs lipid absorption.
AB  - We previously demonstrated increased villus height following genetic deletion, or
      knockout, of retinoblastoma protein (Rb) in the intestinal epithelium (Rb-IKO).
      Here we determined the functional consequences of augmented mucosal growth on
      intestinal fat absorption and following a 50% small bowel resection (SBR). Mice
      with constitutively disrupted Rb expression in the intestinal epithelium (Rb-IKO)
      along with their floxed (wild-type, WT) littermates were placed on a high-fat
      diet (HFD, 42% kcal fat) for 54 wk. Mice were weighed weekly, and fat absorption,
      indirect calorimetry, and MRI body composition were measured. Rb-IKO mice were
      also subjected to a 50% SBR, followed by HFD feeding for 33 wk. In separate
      experiments, we examined intestinal fat absorption in mice with conditional
      (tamoxifen-inducible) intestinal Rb (inducible Rb-IKO) deletion. Microarray
      revealed that the transcriptional expression of lipid absorption/transport genes
      was significantly reduced in constitutive Rb-IKO mice. These mice demonstrated
      greater mucosal surface area yet manifested paradoxically impaired intestinal
      long-chain triglyceride absorption and decreased cholesterol absorption. Despite
      attenuated lipid absorption, there were no differences in metabolic rate, body
      composition, and weight gain in Rb-IKO and WT mice at baseline and following SBR.
      We also confirmed fat malabsorption in inducible Rb-IKO mice. We concluded that,
      despite an expanded mucosal surface area, Rb-IKO mice demonstrate impaired lipid
      absorption without compensatory alterations in energy homeostasis or body
      composition. These findings underscore the importance of delineating
      structural/functional relationships in the gut and suggest a previously unknown
      role for Rb in the regulation of intestinal lipid absorption.

PMID- 24742993
TI  - Involvement and alteration of the Sonic Hedgehog pathway is associated with
      decreased cholesterol level in trisomy 18 and SLO amniocytes.
AB  - BACKGROUND: Trisomy 18 and Smith-Lemli-Opitz syndrome are two polymalformative
      conditions in which a cholesterol defect has been noted. When they occur
      prenatally, they are associated with a decreased maternal unconjugated estriol
      (uE(3)) level. Cholesterol plays an essential role in the Sonic Hedgehog pathway,
      allowing Shh protein maturation leading to its maximal activity. Many
      malformations in these two syndromes occur in Shh dependent tissues. We thus
      sought to assess whether a cholesterol defect could affect the Shh pathway and
      explain some of the observed malformations. MATERIALS AND METHODS: We selected 14
      cases of trisomy 18 and 3 cases of SLO in which the maternal uE(3) level was
      decreased and reported malformations were observed after fetopathological
      examination. We correlated the number of malformations with maternal uE(3) level.
      We then carried out cholesterol concentrations in separate culture media
      consisting of trisomy 18, SLO and control amniocytes. Finally, we analyzed the
      Shh pathway by testing the gene expression of several Shh components: GLI
      transcription factors, BMP2, BMP4, TGFbeta1, COL1A1 and COL1A2. RESULTS AND
      DISCUSSION: There was an inverse correlation between phenotypic severity and
      maternal uE(3) levels in SLO and trisomy 18. The cholesterol levels in the
      amniocyte culture media were correlated with maternal uE3 levels and were
      significantly lower in T18 and SLO amniocytes, reflecting cholesterol defects.
      There was an alteration in the Shh pathway since expression of several genes was
      decreased in T18 and SLO amniocytes. However, these cholesterol defects were not
      solely responsible for the altered Shh pathway and the malformations observed.

PMID- 24742994
TI  - Increased mannitol production in Lactobacillus reuteri ATCC 55730 production
      strain with a modified 6-phosphofructo-1-kinase.
AB  - Based on established knowledge of the simultaneous use of the phosphoketolase
      pathway (PKP) and the Embden-Meyerhof pathway (EMP) - as a secondary pathway with
      a smaller flux - by mannitol producer Lactobacillus reuteri ATCC 55730, we
      demonstrated the hypothesis that by enhancing the flux through the EMP the
      ability of the microorganism to handle elevated glucose concentrations will be
      improved, in addition to its growth rate and biomass yield. NADH availability
      will be increased and its demand will be satisfied, allowing the electron
      acceptor fructose to be more efficiently transformed into mannitol. A truncated
      version of the gene encoding 6-phospho-1-fructokinase (tpfkA) from the NRRL 2270
      strain of Aspergillus niger along with its activator pkaC were introduced into
      the microorganism by plasmid transformation. Growth of the transformants at
      elevated glucose concentrations in the presence of fructose resulted in improved
      assimilation of the provided carbohydrates and a significant increase in the
      overall fermentation productivities. At the highest tested levels of glucose and
      fructose (75g/l each), the transformant strain experienced a 4-fold increase in
      PFK activity and a 2.3-fold increase in the glycolytic flux while the biomass
      yield reached 7g/l (1.6g/l in the parental strain), the mannitol yield was 56g/l
      (10g/l in the parental strain) and the lactate yield was 21g/l (3.5g/l in the
      parental strain). A high NADH/NAD(+) ratio occurred under increased glycolytic
      flux conditions and facilitated the efficient conversion of fructose to mannitol.
      A direct effect of deregulated PFK activity on the glycolytic flux is therefore
      demonstrated in the present case suggesting an alternative approach of metabolic
      engineering in L. reuteri for increased mannitol production. 

PMID- 24742995
TI  - Behaviour of lactic acid bacteria populations in Pecorino di Carmasciano cheese
      samples submitted to environmental conditions prevailing in the gastrointestinal
      tract: evaluation by means of a polyphasic approach.
AB  - The survival of the autochthonous microflora, of samples collected during
      Pecorino di Carmasciano cheese manufacturing, was evaluated along the passage
      through a model mimicking the gastro-intestinal tract. The aim was the selection
      of lactic acid bacteria potentially able to arrive alive and metabolically active
      to the colon. The dynamics of lactic microbiota, throughout simulated digestion
      of cheese samples, were evaluated by means of an approach PCR-DGGE-based.
      Dominant species after cheese digestion could be related to the Lactobacillus
      plantarum and Lactobacillus casei groups. Sixty-three strains, which survived to
      simulated gastro-intestinal transit, were further evaluated for technological
      features and tolerance to human digestion in several experimental conditions,
      according to routinely used protocols. Bacterial survival appeared to be, more
      than strain-specific, strongly affected by experimental conditions, i.e. some
      strains showed an acceptable survival when resuspended in skim milk but not in
      ewe milk and vice versa. Nevertheless according to data, one gram of fresh
      Pecorino di Carmasciano cheese may convey to human colon about the same amount of
      viable LAB of a probiotic drink. Although it cannot be assumed that lactobacilli
      introduced with Pecorino have beneficial effects on the host, the healthy impact
      of autochthonous lactic acid bacteria of naturally fermented food has a broad
      consensus in the current literature. 

PMID- 24742996
TI  - Evaluating food additives as antifungal agents against Monilinia fructicola in
      vitro and in hydroxypropyl methylcellulose-lipid composite edible coatings for
      plums.
AB  - Common food preservative agents were evaluated in in vitro tests for their
      antifungal activity against Monilinia fructicola, the most economically important
      pathogen causing postharvest disease of stone fruits. Radial mycelial growth was
      measured in Petri dishes of PDA amended with three different concentrations of
      the agents (0.01-0.2%, v/v) after 7 days of incubation at 25  degrees C. Thirteen
      out of fifteen agents tested completely inhibited the radial growth of the fungus
      at various concentrations. Among them, ammonium carbonate, ammonium bicarbonate
      and sodium bicarbonate were the most effective while sodium acetate and sodium
      formate were the least effective. The effective agents and concentrations were
      tested as ingredients of hydroxypropyl methylcellulose (HPMC)-lipid edible
      coatings against brown rot disease on plums previously inoculated with M.
      fructicola (curative activity). 'Friar' and 'Larry Ann' plums were inoculated
      with the pathogen, coated with stable edible coatings about 24h later, and
      incubated at 20  degrees C and 90% RH. Disease incidence (%) and severity (lesion
      diameter) were determined after 4, 6, and 8 days of incubation and the 'area
      under the disease progress stairs' (AUDPS) was calculated. Coatings containing
      bicarbonates and parabens significantly reduced brown rot incidence in plums, but
      potassium sorbate, used at 1.0% in the coating formulation, was the most
      effective agent with a reduction rate of 28.6%. All the tested coatings reduced
      disease severity to some extent, but coatings containing 0.1% sodium
      methylparaben or sodium ethylparaben or 0.2% ammonium carbonate or ammonium
      bicarbonate were superior to the rest, with reduction rates of 45-50%. Overall,
      the results showed that most of the agents tested in this study had significant
      antimicrobial activity against M. fructicola and the application of selected
      antifungal edible coatings is a promising alternative for the control of
      postharvest brown rot in plums.

PMID- 24742997
TI  - Filamentous fungal diversity and community structure associated with the solid
      state fermentation of Chinese Maotai-flavor liquor.
AB  - Maotai-flavor liquor is produced by simultaneous saccharification and
      fermentation (SSF) process under solid state conditions, including Daqu (starter)
      making, stacking fermentation and alcohol fermentation stages. Filamentous fungi
      produce many enzymes to degrade the starch material into fermentable sugar during
      liquor fermentation. This study investigated the filamentous fungal community
      associated with liquor making process. Eight and seven different fungal species
      were identified by using culture-dependent and -independent method (PCR
      denaturing gradient gel electrophoresis, DGGE) analyses, respectively. The
      traditional enumeration method showed that Daqu provided 7 fungal species for
      stacking fermentation. The total population of filamentous fungi increased from
      3.4 * 10(3)cfu/g to 1.28 * 10(4)cfu/g in the first 3 days of stacking
      fermentation, and then decreased till the end. In alcohol fermentation in pits,
      the population continuously decreased and few fungal species survived (lower than
      1 * 10(3)cfu/g) after 10 days. Therefore, stacking fermentation is an essential
      stage for the growth of filamentous fungi. Paecilomyces variotii, Aspergillus
      oryzae and Aspergillus terreus were detected by both methods, and P. variotii and
      A. oryzae were the predominant species. Meanwhile, P. variotii possessed the
      highest glucoamylase (3252 +/- 526 U/g) and A. oryzae exhibited the highest alpha
      amylase (1491 +/- 324 U/g) activity among the cultivable fungal species.
      Furthermore, the variation of starch and reducing sugar content was consistent
      with the growth of P. variotii and A. oryzae in Zaopei (fermented grains) during
      stacking fermentation, which implied that the two filamentous fungi played an
      important role in producing amylase for hydrolyzing the starch.

PMID- 24742998
TI  - Histone deacetylase inhibitor valproic acid affects plasmacytoid dendritic cells
      phenotype and function.
AB  - OBJECTIVE: Plasmacytoid dendritic cells (PDC) represent a rare subset of
      dendritic cells specialized in the production of type I IFN in response to
      microbial pathogens. Recent data suggested that histone deacetylase (HDAC)
      inhibitors possess potent immunomodulatory properties both in vitro and in vivo.
      In this study, we assayed the ability of the HDAC inhibitor, valproic acid (VPA),
      to influence the phenotype and functional properties of human PDC isolated from
      peripheral blood. METHODS AND RESULTS: We showed that VPA inhibited the
      production of IFN-alpha and the proinflammatory cytokines TNF-alpha and IL-6 by
      CpG-activated PDC. VPA also affected the phenotype of PDC by reducing the
      expression of costimulatory molecules induced by CpG activation. Moreover, VPA
      reduced the capacity of CpG-stimulated PDC to promote CD4(+) T cell proliferation
      and IFN-gamma production, while enhancing the proportion of IL-10 positive T
      cells. CONCLUSION: These results suggest that HDAC inhibition by VPA alters
      essential human PDC functions, highlighting the need for monitoring immune
      functions in cancer patients receiving HDAC inhibitors, but also making these
      drugs attractive therapies in inflammatory, and autoimmune diseases implicating
      PDC.

PMID- 24742999
TI  - Recombinant phenylalanine ammonia lyase in phenylketonuria.

PMID- 24743000
TI  - Single-dose, subcutaneous recombinant phenylalanine ammonia lyase conjugated with
      polyethylene glycol in adult patients with phenylketonuria: an open-label,
      multicentre, phase 1 dose-escalation trial.
AB  - BACKGROUND: Phenylketonuria is an inherited disease caused by impaired activity
      of phenylalanine hydroxylase, the enzyme that converts phenylalanine to tyrosine,
      leading to accumulation of phenylalanine and subsequent neurocognitive
      dysfunction. Phenylalanine ammonia lyase is a prokaryotic enzyme that converts
      phenylalanine to ammonia and trans-cinnamic acid. We aimed to assess the safety,
      tolerability, pharmacokinetic characteristics, and efficacy of recombinant
      Anabaena variabilis phenylalanine ammonia lyase (produced in Escherichia coli)
      conjugated with polyethylene glycol (rAvPAL-PEG) in reducing phenylalanine
      concentrations in adult patients with phenylketonuria. METHODS: In this open
      label, phase 1, multicentre trial, single subcutaneous injections of rAvPAL-PEG
      were given in escalating doses (0.001, 0.003, 0.010, 0.030, and 0.100 mg/kg) to
      adults with phenylketonuria. Participants aged 18 years or older with blood
      phenylalanine concentrations of 600 MUmol/L or higher were recruited from among
      patients attending metabolic disease clinics in the USA. The primary endpoints
      were safety and tolerability of rAvPAL-PEG. Secondary endpoints were the
      pharmacokinetic characteristics of the drug and its effect on concentrations of
      phenylalanine. Participants and investigators were not masked to assigned dose
      group. This study is registered with ClinicalTrials.gov, number NCT00925054.
      FINDINGS: 25 participants were recruited from seven centres between May 6, 2008,
      and April 15, 2009, with five participants assigned to each escalating dose
      group. All participants were included in the safety population. The most
      frequently reported adverse events were injection-site reactions and dizziness,
      which were self-limited and without sequelae. Two participants had serious
      adverse reactions to intramuscular medroxyprogesterone acetate, a drug that
      contains polyethylene glycol as an excipient. Three of five participants given
      the highest dose of rAvPAL-PEG (0.100 mg/kg) developed a generalised skin rash.
      By the end of the study, all participants had developed antibodies against
      polyethylene glycol, and some against phenylalanine ammonia lyase as well. Drug
      concentrations peaked about 89-106 h after administration of the highest dose.
      Treatment seemed to be effective at reducing blood phenylalanine in all five
      participants who received the highest dose (mean reduction of 54.2% from
      baseline), with a nadir about 6 days after injection and an inverse correlation
      between drug and phenylalanine concentrations in plasma. Phenylalanine returned
      to near-baseline concentrations about 21 days after the injection.
      INTERPRETATION: Subcutaneous administration of rAvPAL-PEG in a single dose of up
      to 0.100 mg/kg was fairly safe and well tolerated in adult patients with
      phenylketonuria. At the highest dose tested, rAvPAL-PEG reduced blood
      phenylalanine concentrations. In view of the development of antibodies against
      polyethylene glycol (and in some cases against phenylalanine ammonia lyase),
      future studies are needed to assess the effect of repeat dosing. FUNDING:
      BioMarin Pharmaceutical.

PMID- 24743001
TI  - A computerized global MR image feature analysis scheme to assist diagnosis of
      breast cancer: a preliminary assessment.
AB  - OBJECTIVES: To develop a new computer-aided detection scheme to compute a global
      kinetic image feature from the dynamic contrast enhanced breast magnetic
      resonance imaging (DCE-MRI) and test the feasibility of using the computerized
      results for assisting classification between the DCE-MRI examinations associated
      with malignant and benign tumors. MATERIALS AND METHODS: The scheme registers
      sequential images acquired from each DCE-MRI examination, segments breast areas
      on all images, searches for a fraction of voxels that have higher contrast
      enhancement values and computes an average contrast enhancement value of selected
      voxels. Combination of the maximum contrast enhancement values computed from two
      post-contrast series in one of two breasts is applied to predict the likelihood
      of the examination being positive for breast cancer. The scheme performance was
      evaluated when applying to a retrospectively collected database including 80
      malignant and 50 benign cases. RESULTS: In each of 91% of malignant cases and 66%
      of benign cases, the average contrast enhancement value computed from the top
      0.43% of voxels is higher in the breast depicted suspicious lesions as compared
      to another negative (lesion-free) breast. In classifying between malignant and
      benign cases, using the computed image feature achieved an area under a receiver
      operating characteristic curve of 0.839 with 95% confidence interval of [0.762,
      0.898]. CONCLUSIONS: We demonstrated that the global contrast enhancement feature
      of DCE-MRI can be relatively easily and robustly computed without accurate breast
      tumor detection and segmentation. This global feature provides supplementary
      information and a higher discriminatory power in assisting diagnosis of breast
      cancer.

PMID- 24743002
TI  - Early oral feeding following thoracolaparoscopic oesophagectomy for oesophageal
      cancer.
AB  - OBJECTIVES: Nil-by-mouth with enteral tube feeding is widely practised for
      several days after resection and reconstruction of oesophageal cancer. This study
      investigates early changes in postoperative gastric emptying and the feasibility
      of early oral feeding after thoracolaparoscopic oesophagectomy for patients with
      oesophageal cancer. METHODS: Between January 2013 and August 2013, gastric
      emptying of liquid food and the feasibility of early oral feeding after
      thoracolaparoscopic oesophagectomy was investigated in 68 patients. Sixty-five
      patients previously managed in the same unit who routinely took liquid food 7
      days after thoracolaparoscopic oesophagectomy served as controls. RESULTS: The
      mean preoperative half gastric emptying time (GET1/2) was 66.4 +/- 38.4 min for
      all 68 patients, and the mean GET1/2 at postoperative day (POD) 1 and POD 7 was
      statistically significantly shorter than preoperative GET1/2 (23.9 +/- 15.7 min
      and 24.1 +/- 7.9 min, respectively, both P-values <0.001). Of the 68 patients who
      were enrolled to analyse the feasibility of early oral feeding, 2 (3.0%) patients
      could not take food as early as planned. The rate of total complication was 20.6%
      (14/68) and 29.2% (19/65) in the early oral feeding group and the late oral
      feeding group, respectively (P = 0.249). Compared with the late oral feeding
      group, time to first flatus and bowel movement was significantly shorter in the
      early oral feeding group. CONCLUSIONS: Compared with preoperative gastric
      emptying, early postoperative gastric emptying for liquid food after
      oesophagectomy is significantly faster. Postoperative early oral feeding in
      patients with thoracolaparoscopic oesophagectomy is feasible and safe.

PMID- 24743003
TI  - Emergency open surgery for aorto-oesophageal and aorto-bronchial fistulae after
      thoracic endovascular aortic repair: a single-centre experience?.
AB  - OBJECTIVES: Severe complications after thoracic endovascular aortic repair
      (TEVAR), such as secondary aorto-oesophageal (AOF) or aorto-bronchial fistulae
      (ABF), are most likely under-reported; however, once detected, emergent surgery
      becomes necessary. METHODS: Between June 2002 and September 2013, 10 (2.6%) of
      374 patients (8 males; mean age 68 years, range: 49-77) were admitted with AOF (n
      = 8) or ABF (n = 2) post-TEVAR during follow-up (mean 12.9 months, range 0.2
      48.1). The respective Ishimaru landing zones were 0 (n = 1), 2 (n = 3), 3 (n = 4)
      and 4 (n = 2). Median interval between TEVAR and AOF/ABF formation was 18.1
      months (range 0.1-65.1). Symptoms on admission included haematemesis (n = 4),
      haemoptysis (n = 2), melena (n = 1), elevated C-reactive protein (n = 10), new
      onset fever (n = 3), positive blood cultures (n = 8), dysphagia (n = 1), chest
      pain (n = 4), previous syncope (n = 1) and vertigo (n = 1). In 6 patients with
      AOF, stent graft removal required ascending aortic (n = 1), aortic arch (n = 1),
      left hemiarch (n = 2) and descending aortic (n = 6) replacement with concomitant
      oesophagectomy (n = 4) and cervical oesophagostomy (n = 1) or oesophageal repair
      (n = 2); another patient with AOF underwent oesophagectomy and cervical
      oesophagostomy via posterolateral thoracotomy without stent graft removal as a
      first-stage operation. One patient with ABF was treated by stent graft removal,
      aortic arch and descending aortic replacement in combination with bronchial
      repair. Two patients were deemed inoperable and treated conservatively. RESULTS:
      All patients survived the operation. Reoperation due to postoperative
      mediastinitis, haemorrhage, pericardial tamponade and wound infection was
      required in 4 (50%, 95% confidence interval [CI] [22, 78]) patients. In-hospital
      mortality was 25% (n = 2; 95% CI [7, 59]) due to mediastinitis with resulting
      multiorgan failure (n = 1) and aortic rupture with haemorrhagic shock (n = 1).
      One patient died due to unknown cause on postoperative day 158. No neurological
      complications occurred postoperatively. Postoperative complications comprised
      acute renal failure with temporary dependence on haemodialysis (n = 2) and
      respiratory insufficiency (n = 4) requiring percutaneous tracheostomy (n = 2).
      Both patients treated conservatively died after 4 and 81 days due to pulmonary
      haemorrhage and fulminant mediastinitis, respectively. CONCLUSIONS: AOF and ABF
      represent uncommon but fatal complications-if treated conservatively-after TEVAR
      that may occur during short- and mid-term follow-up. Surgery for AOF/ABF requires
      early diagnosis and should be performed promptly and in a radical fashion to
      totally excise all infected tissues in these high-risk patients.

PMID- 24743004
TI  - Stent grafting: purpose or means.

PMID- 24743005
TI  - Valve-sparing aortic root replacement?.
AB  - OBJECTIVES: To evaluate our results of valve-sparing aortic root replacement and
      associated (multiple) valve repair. METHODS: From September 2003 to September
      2013, 97 patients had valve-sparing aortic root replacement procedures. Patient
      records and preoperative, postoperative and recent echocardiograms were reviewed.
      Median age was 40.3 (range: 13.4-68.6) years and 67 (69.1%) were male. Seven
      (7.2%) patients were younger than 18 years, the youngest being 13.4 years. Fifty
      four (55.7%) had Marfan syndrome, 2 (2.1%) other fibrous tissue diseases, 15
      (15.5%) bicuspid aortic valve and 3 (3.1%) had earlier Fallot repair. The
      reimplantation technique was used in all, with a straight vascular prosthesis in
      11 (26-34 mm) and the Valsalva prosthesis in 86 (26-32 mm). Concomitant aortic
      valve repair was performed in 43 (44.3%), mitral valve repair in 10 (10.3%),
      tricuspid valve repair in 5 (5.2%) and aortic arch replacement in 3 (3.1%).
      RESULTS: Mean follow-up was 4.2 +/- 2.4 years. Follow-up was complete in all. One
      14-year old patient died 1.3 years post-surgery presumably of ventricular
      arrhythmia. One patient underwent reoperation for aneurysm of the proximal right
      coronary artery after 4.9 years and 4 patients required aortic valve replacement,
      3 of which because of endocarditis after 0.1, 0.8 and 1.3 years and 1 because of
      cusp prolapse after 3.8 years. No thrombo-embolic complications occurred.
      Mortality, root reoperation and aortic regurgitation were absent in 88.0 +/- 0.5%
      at 5-year follow-up. CONCLUSIONS: Results of valve-sparing root replacement are
      good, even in association with a high incidence of concomitant valve repair.
      Valve-sparing aortic root replacement can be performed at a very young age as
      long as an adult size prosthesis can be implanted.

PMID- 24743006
TI  - Lifetime cost effectiveness of a through-school nutrition and physical programme:
      Project Energize.
AB  - Project Energize, a multicomponent through-school physical activity and nutrition
      programme, is delivered to all primary school children in the Waikato region. The
      programme aim is to improve the overall health and reduce the rate of weight gain
      of all Waikato primary school children. An existing economic model was used to
      extrapolate the programme effects, initial costs, lifetime health treatment cost
      structures, quality-adjusted-life-years gained and increased life expectancy to
      the general and Maori child population of New Zealand. In March 2011, a sample of
      2474 younger (7.58 +/- 0.57 years, mean +/- SD) and 2330 older (10.30 +/- 0.51
      years) children (36% Maori) attending Energize schools had body mass index
      measured and compared using mixed effect modelling with unEnergized comparison
      children from 2004 and 2006 from the same region. In 2011 the median body mass
      index reduction compared with the comparison younger children was -0.504 (90% CI 
      0.435 to -0.663) kg/m(2) and in the older children -0.551 (-0.456 to -0.789)
      kg/m(2). In 2010 there were 42,067 children attending Energize schools and in the
      same year NZ$1,891,175 was spent to deliver the programme; a cost of
      $44.96/child/year. Compared to the comparison children the increment in
      cost/quality-adjusted-life-year gained was $30,438 for the younger and $24,690
      for the older children, and lower for Maori (younger $28,241, older $22,151) and
      for the middle socioeconomic status schools ($23,211, $17,891). Project Energize
      would improve quality and length of life and when compared with other obesity
      prevention programmes previously assessed with this model, it would be relatively
      cost-effective from the health treatment payer's perspective.

PMID- 24743007
TI  - Patient and physician characteristics associated with the provision of weight
      loss counseling in primary care.
AB  - BACKGROUND: A variety of physician and patient characteristics may influence
      whether weight loss counseling occurs in primary care encounters. OBJECTIVES:
      This study utilized a cross-sectional survey of primary care patients, which
      examined patient characteristics, physician characteristics, and characteristics
      of the physiciana??patient relationship associated with weight loss counseling
      and recommendations provided by physicians. PARTICIPANTS: (N = 143, mean age =
      46.8 years, mean BMI = 36.9 kg/m(2), 65% Caucasian) were overweight and obese
      primary care patients participating in a managed care weight loss program.
      MEASURES: PARTICIPANTS completed self-report surveys in the clinic prior to the
      initial weight loss session. Surveys included items assessing
      demographic/background characteristics, weight, height, and a health care
      questionnaire evaluating whether their physician had recommended weight loss, the
      frequency of their physiciansa?? weight loss counseling, and whether their
      physician had referred them for obesity treatment. RESULTS: Patient BMI and
      physician sex were most consistently associated with physiciansa?? weight loss
      counseling practices. Patients seen by female physicians were more likely to be
      told that they should lose weight, received more frequent obesity counseling, and
      were more likely to have been referred for obesity treatment by their physician.
      Length and frequency of physiciana??patient contacts were unrelated to the
      likelihood of counseling. CONCLUSIONS: These findings add to previous evidence
      suggesting possible differences in the weight loss counseling practices of male
      and female physicians, although further research is needed to understand this
      potential difference between physicians.

PMID- 24743008
TI  - The impact of physician weight discussion on weight loss in US adults.
AB  - PROBLEM: The increasing prevalence of overweight and obesity in the United States
      and worldwide is at epidemic levels. Physicians may play a vital role in
      addressing this epidemic. We aimed to examine the association of a physician's
      discussion of patients' weight status with self-reported weight loss. We
      hypothesized that physician discussion of patients' being overweight is
      associated with increased weight loss in patients with overweight and obesity.
      METHODS: Data analysis of participants (n = 5054) in the National Health and
      Nutritional Examination Survey (NHANES) in 2005-2008. The main outcome was rates
      of self-reported weight loss and the association with physicians' discussion of
      their patients' weight status. RESULTS: Overweight and obese participants were
      significantly more likely to report a 5% weight loss in the past year if their
      doctor had told them they were overweight (adjusted OR (AOR) 1.88; 95% CI 1.45
      2.44; AOR 1.79; 95% CI 1.30-2.46, respectively). CONCLUSIONS: Physicians' direct
      discussion of their patients' weight status is associated with clinically
      significant patient weight loss and may be a targetable intervention. Further
      studies are needed to determine if increasing physician discussion of patients'
      weight status leads to significant weight loss.

PMID- 24743009
TI  - GPs, families and children's perceptions of childhood obesity.
AB  - BACKGROUND: Childhood obesity has a high risk of becoming a chronic disease
      requiring life-long weight management. Evidence based guidelines were developed
      and distributed to GPs throughout Australia by the NHMRC, but current application
      falls short. Measuring height and weight, and calculating BMI for children
      appears to be rare. Some general practitioners (GPs) perceive significant
      barriers to managing this patient cohort, and patients report not having
      confidence in their GPs. AIM: To explore perceptions and experiences of treating
      childhood obesity of (i) GPs, (ii) families involved in a childhood obesity study
      in general practicea?? and (iii) families not involved in the project, but who
      had concerns about childhood obesity. METHODOLOGY: Supported by the literature, a
      semi-structured schedule was developed to address the aims. Ten GPs and eight
      families involved, and four families previously not involved in the project
      participated in interviews in 2009. All family interviews were audio-taped and
      transcribed verbatim. Data were thematically analyzed. FINDINGS: Five themes
      emerged: (1) raising the topic, (2) frustrations experienced by GPs and families,
      (3) support available for GPs to provide to families and/or anticipated by
      families, (4) successes from involvement in the project and (5) sustaining
      improvements a?? the GPsa?? and family's perspectives. DISCUSSION AND CONCLUSION:
      All acknowledged that childhood obesity is a sensitive issue with both GPs and
      parents preferring the other to raise the topic. GPs reported successes in
      practice and patient management such as improved patient records. For families,
      the GPs dedication and support were major factors sought.

PMID- 24743010
TI  - A preliminary investigation of the role of self-control in behavioral weight loss
      treatment.
AB  - Self-control is associated with positive health outcomes; however, there is
      limited information on self-control and weight loss. Thus, the purpose of this
      preliminary research was to examine how objectively measured self-control
      operates within the context of a behavioral weight loss program (BWL). Results
      showed that greater self-control and increases in self-control during BWL
      treatment were associated with greater weight loss (r's a?Y 0.26; p's < 0.05),
      better treatment attendance (r's a?Y 0.26; p < 0.05), adherence to a low fat diet
      (r'sa? -0.37; p's < 0.05), and greater increases in physical activity (r's a?Y
      0.46; p's < 0.05). These preliminary findings suggest that self-control may play
      an important role in weight loss success.

PMID- 24743012
TI  - Associations between adolescent and adult socioeconomic status and risk of
      obesity and overweight in Danish adults.
AB  - BACKGROUND: It has been suggested that socioeconomic status (SES) may influence
      the risk of obesity; however it is important to consider individual changes in
      SES over the life-course in addition to SES at specific time-points to better
      understand the complex associations with obesity. We explored the relationship
      between lifetime-specific and life-course SES and risk of obesity and overweight
      in Danish adults. METHODS: Data were used from the Danish Youth and Sports Study
      (DYSS) - a 20-22 year follow-up study of Danish teenagers born between 1964 and
      1969. Baseline data gathered in 1983 and 1985 included self-reported BMI, SES and
      physical activity. The follow-up survey (2005) repeated these assessments in
      addition to an assessment of diet. Complete data on adolescent and adult SES and
      BMI were available for 623 participants. RESULTS: Following adjustments,
      adolescent SES had no significant association with overweight/obesity in this
      sample, however females of low or medium adult SES were significantly more likely
      to be overweight/obese compared to those of high SES (low SES: OR: 2.7; 95% CI:
      (1.3-5.8); p = 0.008; medium SES: OR: 4.0, 95% CI (1.6-10.2); p = 0.003). Females
      who decreased in SES during adulthood were significantly more likely to be
      overweight/obese compared to those who remained of high SES (OR: 3.1; 95% CI (1.1
      9.2); p = 0.04). CONCLUSION: Effects of early life-factors may be conditional
      upon the environment in adulthood, particularly for the women. Further research
      should consider the timing of SES exposure and the mechanisms which may be
      responsible for the socioeconomic gradients in prevalence of obesity and
      overweight.

PMID- 24743011
TI  - Optimal waist circumference cut-off values for predicting cardiovascular risk
      factors in a multi-ethnic Malaysian population.
AB  - INTRODUCTION: Previous studies have proposed the lower waist circumference (WC)
      cutoffs be used for defining abdominal obesity in Asian populations. OBJECTIVE:
      To determine the optimal cut-offs of waist circumference (WC) in predicting
      cardiovascular (CV) risk factors in the multi-ethnic Malaysian population.
      METHODS: We analysed data from 32,703 respondents (14,980 men and 17,723 women)
      aged 18 years and above who participated in the Third National Health and
      Morbidity Survey in 2006. Gender-specific logistic regression analyses were used
      to examine associations between WC and three CV risk factors (diabetes mellitus,
      hypertension, and hypercholesterolemia). The Receiver Operating Characteristic
      (ROC) curves were used to determine the cut-off values of WC with optimum
      sensitivity and specificity for detecting these CV risk factors. RESULTS: The
      odds ratio for having diabetes mellitus, hypertension, and hypercholesterolemia,
      or at least one of these risks, increased significantly as the WC cut-off point
      increased. Optimal WC cut-off values for predicting the presence of diabetes
      mellitus, hypertension, hypercholesterolemia and at least one of the three CV
      risk factors varied from 81.4 to 85.5 cm for men and 79.8 to 80.7 cm for women.
      CONCLUSIONS: Our findings indicate that WC cut-offs of 81 cm for men and 80 cm
      for women are appropriate for defining abdominal obesity and for recommendation
      to undergo cardiovascular risk screening and weight management in the Malaysian
      adult population.

PMID- 24743013
TI  - The effect of educational status on the relationship between obesity and risk of
      type 2 diabetes.
AB  - OBJECTIVE: Obesity trends are likely to increase social disparities in diabetes.
      The magnitude of this effect depends on the strength of the relationship between
      obesity and diabetes across categories of disadvantage. This study aims to test
      the hypothesis that education level moderates the association between obesity and
      fasting plasma glucose (FPG), 2-h plasma glucose (2hPG), HbA1c level, and
      diabetes prevalence. METHODS: We used the baseline data from the Australian
      Obesity, Diabetes, and Lifestyle study in 2000 (n = 8646). We performed multiple
      linear regression analysis adjusted for confounding factors and stratified by
      education level. Body mass index (BMI) and waist circumference (WC) were
      positively associated with FPG, 2hPG, HbA1c and prevalence of diabetes. RESULTS:
      No moderating effect of education on these relationships was observed in the
      total population. In never smokers free of diagnosed diabetes at baseline the
      association of WC with 2hPG and HbA1c and of BMI with HbA1c was stronger in those
      with a lower level of education. CONCLUSIONS: Overall, these results suggest that
      the association between obesity and diabetes risk is independent of educational
      status. However, inconsistent results suggest that further analyses of an
      adequately powered longitudinal study of never smokers free of diabetes would be
      useful to further explore this hypothesis.

PMID- 24743014
TI  - Obesity is associated with retinopathy and macrovascular disease in type 1
      diabetes.
AB  - Excessive body weight is increasingly seen in type 1 diabetes but its impact is
      debated. To address this uncertainty, we aimed to determine the association
      between excess body weight and the macro- and microvascular complications of type
      1 diabetes. We identified 501 adults with type 1 diabetes attending an Australian
      hospital clinic and extracted their clinical and biochemical data from our
      patient management database. In both men and women, obesity (BMI > 30 kg/m(2))
      was the predominant risk factor for retinopathy and cardiovascular disease
      despite similar HbA1c and increased use of cardioprotective drugs compared to non
      obese patients. Obesity was associated with albuminuria in women, but not renal
      impairment or neuropathy in either sex. We conclude that obesity in type 1
      diabetes may promote retinopathy and macrovascular disease. Future trials to
      determine the effect of weight loss on type 1 diabetes in obese people are
      needed.

PMID- 24743015
TI  - Food tolerance and diet quality following adjustable gastric banding, sleeve
      gastrectomy and Roux-en-Y gastric bypass.
AB  - OBJECTIVE: The effects of food tolerance (if any) on diet quality several years
      post-surgery remain unclear. Our study aimed to assess food tolerance and diet
      quality after three bariatric procedures; adjustable gastric banding (AGB),
      sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGBP), 2a??4 years post
      surgery. METHODS: This prospective, cross-sectional study assessed weight loss,
      food tolerance and diet quality in 130 subjects (14 obese pre-surgical controls,
      13 AGB, 62 SG and 41 RYGBP). Inclusion criteria selected patients who underwent
      bariatric surgery between 1 January 2007 and 31 December 2008, at a single
      bariatric clinic. Non-parametric tests (Kruksala??Wallis and Manna??Whitney)
      along with Spearman's correlation coefficient analysis were used. RESULTS:
      Superior food tolerance was reported by the control (24.5), SG (24.0) and RYGBP
      (22.0) groups, compared with the AGB group (15.5; P < 0.001). The control and AGB
      groups consumed significantly more high-calorie extra foods (9.2 and 7.7 daily
      serves respectively) compared with the SG (3.4 serves) and RYGBP (4.0 serves)
      groups. There were several significant correlations between food tolerance and
      dietary intake including breads and cereals and meat and meat alternatives.
      CONCLUSION: The control and AGB groups consumed significantly more high-calorie
      extra foods, a result that was paralleled by poor weight loss and food tolerance
      outcomes for the AGB group. A significant positive relationship between food
      tolerance and diet quality was established. Poor food tolerance and thus
      compromised diet quality need to be considered as post-surgical complications of
      the AGB procedure.

PMID- 24743016
TI  - Body weight perception and weight loss practices among Sri Lankan adults.
AB  - OBJECTIVES: The purpose of the present study was to evaluate the association
      between self-perception of body weight, weight loss approaches and measured body
      mass index (BMI) and waist circumference (WC) among Sri Lankan adults. METHODS: A
      nationally representative sample of 600 adults aged >=18 years was selected using
      a multi-stage random cluster sampling technique. An interviewer-administrated
      questionnaire was used to assess demographic characteristics, body weight
      perception, abdominal obesity perception and details of weight losing practices.
      Weight, height and waist circumference (WC) were measured and Asian
      anthropometric cut-offs for BMI and WC were applied. RESULTS: Body weight mis
      perception was common among Sri Lankan adults. Two-thirds of overweight males and
      44.7% females considered themselves as 'about right weight', moreover, 4.1% and
      7.6% overweight men and women reported themselves as being 'underweight'. Over
      one third of both male and female obese subjects perceived themselves as 'about
      right weight' or 'underweight'. Nearly 32% of centrally obese men and women
      perceived that their WC is about right. People who perceived themselves as
      overweight or very overweight (n = 154) only 63.6% tried to lose weight (n = 98),
      and one quarter of adults sought advice from professionals (n = 39). CONCLUSION:
      Body weight misperception was common among underweight, healthy weight,
      overweight, and obese adults in Sri Lanka. Over 2/3 of overweight and 1/3 of
      obese Sri Lankan adults believe they are in right weight category or are under
      weight.

PMID- 24743017
TI  - NEDD4 controls the expression of GUCD1, a protein upregulated in proliferating
      liver cells.
AB  - Liver regeneration is a unique means of studying cell proliferation in vivo.
      Screening of a large cDNA library from regenerating liver has previously allowed
      us to identify and characterize a cluster of genes encoding proteins with
      important roles in proliferative processes. Here, by examining different rat and
      human tissues as well as cell lines, we characterized a highly conserved gene,
      guanylyl cyclase domain containing 1 (GUCD1), whose modulation occurs in liver
      regeneration and cell cycle progression in vitro. High-level expression of GUCD1
      transcripts was observed in livers from patients with hepatocellular carcinoma. A
      yeast two-hybrid interaction assay, aimed at identifying any relevant interaction
      partners of GUCD1, revealed direct interactions with NEDD4-1 (E3 ubiquitin
      protein ligase neural precursor cell expressed, developmentally downregulated
      gene 4), resulting in control of GUCD1 stability. Thus, we have characterized
      expression and function of a ubiquitous protein, GUCD1, which might have a role
      in regulating normal and abnormal cell growth in the liver. 

PMID- 24743018
TI  - Detection of IL-17A-producing peripheral blood monocytes in Langerhans cell
      histiocytosis patients.
AB  - Langerhans cell histiocytosis (LCH) is a rare disease of unknown cause with
      manifestations ranging from isolated granulomatous lesions to life-threatening
      multi-system organ involvement. This disorder is further characterized by
      infiltration of immune cells in affected tissues and an association with
      interleukin (IL)-17A has been reported. Here, we investigated the presence of IL
      17A-producing cells among peripheral blood mononuclear cells isolated from LCH
      patients and observed a high percentage of IL-17A(+) monocytes in peripheral
      blood of LCH patients compared to controls. The IL-17A(+) monocytes were also
      positive for the transcription factor retinoic acid orphan receptor (ROR) gammat
      and showed increased mRNA levels for both IL-17A and RORgammat. Notably, IL-17A
      was produced by all monocyte subsets and the expression level was positively
      associated with LCH disease activity. These data support a role for monocytes in
      the pathogenesis of LCH. Future therapeutic approaches may consider
      identification of patients who may benefit from IL-17A-targeted interventions.

PMID- 24743019
TI  - Successful interferon-alpha 2b therapy for unremitting warts in a patient with
      DOCK8 deficiency.
AB  - The autosomal recessive form of the Hyper IgE syndrome (AR-HIES) with dedicator
      of cytokinesis 8 (DOCK8) deficiency is associated with difficult to treat
      persistent viral skin infections, including papilloma virus infection. Type I
      interferons play an important role in the defense against viruses. We examined
      the effect of therapy with IFN-alpha 2b in an 11-year old boy with DOCK8
      deficiency due to a homozygous splice donor site mutation in DOCK8 intron 40. His
      unremitting warts showed dramatic response to IFN-alpha 2b therapy. Immunological
      studies revealed decreased circulating plasmacytoid dendritic cells (pDCs) and
      profound deficiency of IFN-alpha production by his peripheral blood mononuclear
      cells in response to treatment with CpG oligonucleotides. These findings indicate
      that underlying pDC deficiency and impaired IFN-alpha production may predispose
      to chronic viral infections in DOCK8 deficiency. IFN-alpha 2b therapy maybe
      useful in controlling recalcitrant viral infections in these patients. 

PMID- 24743020
TI  - Automatic classification of epilepsy types using ontology-based and genetics
      based machine learning.
AB  - OBJECTIVES: In the presurgical analysis for drug-resistant focal epilepsies, the
      definition of the epileptogenic zone, which is the cortical area where ictal
      discharges originate, is usually carried out by using clinical,
      electrophysiological and neuroimaging data analysis. Clinical evaluation is based
      on the visual detection of symptoms during epileptic seizures. This work aims at
      developing a fully automatic classifier of epileptic types and their localization
      using ictal symptoms and machine learning methods. METHODS: We present the
      results achieved by using two machine learning methods. The first is an ontology
      based classification that can directly incorporate human knowledge, while the
      second is a genetics-based data mining algorithm that learns or extracts the
      domain knowledge from medical data in implicit form. RESULTS: The developed
      methods are tested on a clinical dataset of 129 patients. The performance of the
      methods is measured against the performance of seven clinicians, whose level of
      expertise is high/very high, in classifying two epilepsy types: temporal lobe
      epilepsy and extra-temporal lobe epilepsy. When comparing the performance of the
      algorithms with that of a single clinician, who is one of the seven clinicians,
      the algorithms show a slightly better performance than the clinician on three
      test sets generated randomly from 99 patients out of the 129 patients. The
      accuracy obtained for the two methods and the clinician is as follows: first test
      set 65.6% and 75% for the methods and 56.3% for the clinician, second test set
      66.7% and 76.2% for the methods and 61.9% for the clinician, and third test set
      77.8% for the methods and the clinician. When compared with the performance of
      the whole population of clinicians on the rest 30 patients out of the 129
      patients, where the patients were selected by the clinicians themselves, the mean
      accuracy of the methods (60%) is slightly worse than the mean accuracy of the
      clinicians (61.6%). Results show that the methods perform at the level of
      experienced clinicians, when both the methods and the clinicians use the same
      information. CONCLUSION: Our results demonstrate that the developed methods form
      important ingredients for realizing a fully automatic classification of epilepsy
      types and can contribute to the definition of signs that are most important for
      the classification.

PMID- 24743022
TI  - Inhibitors of the 5-lipoxygenase arachidonic acid pathway induce ATP release and
      ATP-dependent organic cation transport in macrophages.
AB  - We have previously described that arachidonic acid (AA)-5-lipoxygenase (5-LO)
      metabolism inhibitors such as NDGA and MK886, inhibit cell death by apoptosis,
      but not by necrosis, induced by extracellular ATP (ATPe) binding to P2X7
      receptors in macrophages. ATPe binding to P2X7 also induces large cationic and
      anionic organic molecules uptake in these cells, a process that involves at least
      two distinct transport mechanisms: one for cations and another for anions. Here
      we show that inhibitors of the AA-5-LO pathway do not inhibit P2X7 receptors, as
      judged by the maintenance of the ATPe-induced uptake of fluorescent anionic dyes.
      In addition, we describe two new transport phenomena induced by these inhibitors
      in macrophages: a cation-selective uptake of fluorescent dyes and the release of
      ATP. The cation uptake requires secreted ATPe, but, differently from the
      P2X7/ATPe-induced phenomena, it is also present in macrophages derived from mice
      deficient in the P2X7 gene. Inhibitors of phospholipase A2 and of the AA
      cyclooxygenase pathway did not induce the cation uptake. The uptake of non
      organic cations was investigated by measuring the free intracellular Ca(2+)
      concentration ([Ca(2+)]i) by Fura-2 fluorescence. NDGA, but not MK886, induced an
      increase in [Ca(2+)]i. Chelating Ca(2+) ions in the extracellular medium
      suppressed the intracellular Ca(2+) signal without interfering in the uptake of
      cationic dyes. We conclude that inhibitors of the AA-5-LO pathway do not block
      P2X7 receptors, trigger the release of ATP, and induce an ATP-dependent uptake of
      organic cations by a Ca(2+)- and P2X7-independent transport mechanism in
      macrophages. 

PMID- 24743021
TI  - Two interdependent mechanisms of antimicrobial activity allow for efficient
      killing in nylon-3-based polymeric mimics of innate immunity peptides.
AB  - Novel synthetic mimics of antimicrobial peptides have been developed to exhibit
      structural properties and antimicrobial activity similar to those of natural
      antimicrobial peptides (AMPs) of the innate immune system. These molecules have a
      number of potential advantages over conventional antibiotics, including reduced
      bacterial resistance, cost-effective preparation, and customizable designs. In
      this study, we investigate a family of nylon-3 polymer-based antimicrobials. By
      combining vesicle dye leakage, bacterial permeation, and bactericidal assays with
      small-angle X-ray scattering (SAXS), we find that these polymers are capable of
      two interdependent mechanisms of action: permeation of bacterial membranes and
      binding to intracellular targets such as DNA, with the latter necessarily
      dependent on the former. We systemically examine polymer-induced membrane
      deformation modes across a range of lipid compositions that mimic both bacteria
      and mammalian cell membranes. The results show that the polymers' ability to
      generate negative Gaussian curvature (NGC), a topological requirement for
      membrane permeation and cellular entry, in model Escherichia coli membranes
      correlates with their ability to permeate membranes without complete membrane
      disruption and kill E. coli cells. Our findings suggest that these polymers
      operate with a concentration-dependent mechanism of action: at low concentrations
      permeation and DNA binding occur without membrane disruption, while at high
      concentrations complete disruption of the membrane occurs. This article is part
      of a Special Issue entitled: Interfacially Active Peptides and Proteins. Guest
      Editors: William C. Wimley and Kalina Hristova. 

PMID- 24743023
TI  - Peptide:lipid ratio and membrane surface charge determine the mechanism of action
      of the antimicrobial peptide BP100. Conformational and functional studies.
AB  - The cecropin-melittin hybrid antimicrobial peptide BP100 (H-KKLFKKILKYL-NH2) is
      selective for Gram-negative bacteria, negatively charged membranes, and weakly
      hemolytic. We studied BP100 conformational and functional properties upon
      interaction with large unilamellar vesicles, LUVs, and giant unilamellar
      vesicles, GUVs, containing variable proportions of phosphatidylcholine (PC) and
      negatively charged phosphatidylglycerol (PG). CD and NMR spectra showed that upon
      binding to PG-containing LUVs BP100 acquires alpha-helical conformation, the
      helix spanning residues 3-11. Theoretical analyses indicated that the helix is
      amphipathic and surface-seeking. CD and dynamic light scattering data evinced
      peptide and/or vesicle aggregation, modulated by peptide:lipid ratio and PG
      content. BP100 decreased the absolute value of the zeta potential (zeta) of LUVs
      with low PG contents; for higher PG, binding was analyzed as an ion-exchange
      process. At high salt, BP100-induced LUVS leakage requires higher peptide
      concentration, indicating that both electrostatic and hydrophobic interactions
      contribute to peptide binding. While a gradual release took place at low
      peptide:lipid ratios, instantaneous loss occurred at high ratios, suggesting
      vesicle disruption. Optical microscopy of GUVs confirmed BP100-promoted
      disruption of negatively charged membranes. The mechanism of action of BP100 is
      determined by both peptide:lipid ratio and negatively charged lipid content.
      While gradual release results from membrane perturbation by a small number of
      peptide molecules giving rise to changes in acyl chain packing, lipid clustering
      (leading to membrane defects), and/or membrane thinning, membrane disruption
      results from a sequence of events - large-scale peptide and lipid clustering,
      giving rise to peptide-lipid patches that eventually would leave the membrane in
      a carpet-like mechanism. 

PMID- 24743025
TI  - Achievements of the FIGO Initiative for the Prevention of Unsafe Abortion and its
      Consequences in South-Southeast Asia.
AB  - Since 2008, the FIGO Initiative for the Prevention of Unsafe Abortion and its
      Consequences has contributed to ensuring the substitution of sharp curettage by
      manual vacuum aspiration (MVA) and medical abortion in selected hospitals in
      participating countries of South-Southeast Asia. This initiative facilitated the
      registration of misoprostol in Pakistan and Bangladesh, and the approval of
      mifepristone for "menstrual regulation" in Bangladesh. The Pakistan Nursing
      Council agreed to include MVA and medical abortion in the midwifery curriculum.
      The Bangladesh Government has approved the training of nurses and paramedics in
      the use of MVA to treat incomplete abortion in selected cases. The Sri Lanka
      College of Obstetricians and Gynaecologists, in collaboration with partners, has
      presented a draft petition to the relevant authorities appealing for them to
      liberalize the abortion law in cases of rape and incest or when lethal congenital
      abnormalities are present. Significantly, the initiative has introduced or
      strengthened the provision of postabortion contraception. 

PMID- 24743026
TI  - Replacement of dilation and curettage/evacuation by manual vacuum aspiration and
      medical abortion, and the introduction of postabortion contraception in Pakistan.
AB  - Manual vacuum aspiration (MVA) and medical abortion were introduced to replace
      dilation and curettage/evacuation for incomplete abortions, and postabortion
      contraception was provided in 5 selected public hospitals in Pakistan. In the
      largest hospital, an Ipas MVA training center since 2007, MVA use reached 21% in
      2008. After the International Federation of Gynecology and Obstetrics (FIGO) and
      UNFPA provided MVA kits, MVA use increased dramatically to 70%-90% in 2010-2013.
      In 2 of the remaining 4 hospitals in which the Society of Obstetricians and
      Gynecologists of Pakistan trained doctors in May 2012 and January 2013, the
      target of having 50% of women managed by MVA and medical abortion (MA) was met;
      however, in the third hospital only 43% were treated with MVA and MA. In the
      fourth hospital, where misoprostol and electric vacuum aspiration use was 64% and
      9%, respectively, before training, an MVA workshop introduced the technique.
      Postabortion contraception was provided to 9%-29% of women, far below the target
      of 60%. 

PMID- 24743027
TI  - Unobtrusive ECG monitoring in the NICU using a capacitive sensing array.
AB  - The thin skin of preterm babies is easily damaged by adhesive electrodes, tapes,
      chest drains and needle-marks. The scars caused could be disfiguring or disabling
      to 10% of preterm newborns. Capacitive sensors present an attractive option for
      pervasively monitoring neonatal ECG, and can be embedded in a support system or
      even a garment worn by the neonate. This could improve comfort and reduce pain
      aiding better recovery as well as avoiding the scars caused by adhesive
      electrodes. In this work, we investigate the use of an array of capacitive
      sensors unobtrusively embedded in a mattress and used in a clinical environment
      for 15 preterm neonates. We also describe the analysis framework including the
      fusion of information from all sensors to provide a more accurate ECG signal. We
      propose a channel selection strategy as well as a method using physiological
      information to obtain a reliable ECG signal. When sensor coverage is well
      attained, results for both instantaneous heart rate and ECG signal shape analysis
      are very encouraging. The study also provides several insights on important
      factors affecting the results. These include the effect of textile type, number
      of layers, interferences (e.g. people walking by), motion severity and
      interventions. Incorporating this knowledge in the design of a capacitive sensing
      system would be crucial in ensuring that these sensors provide a reliable ECG
      signal when embedded in a neonatal support system. 

PMID- 24743028
TI  - Microbial tolerance engineering toward biochemical production: from
      lignocellulose to products.
AB  - Microbial metabolic engineering has been extensively studied for valuable
      chemicals synthesis, generating numerous laboratory-scale successes, and has
      demonstrated its potential to serve as a platform that enables large-scale
      manufacturing of many chemicals that are currently derived via chemical
      synthesis. However, the commercialization potential of microbial chemical
      production frequently suffers from low productivity and yields, where one key
      limiting factor is the inherently low tolerance of host cells against toxic
      compounds that are present and/or generated during biological processing.
      Consequently, various microbial engineering strategies have been devised to endow
      producer microbes with tolerance phenotypes that would be required for
      economically viable production of the desired chemicals. In this review, we
      discuss key microbial engineering strategies, devised primarily based on rational
      and evolutionary methodologies, that have been effective in improving cellular
      tolerance against fermentation inhibitors, metabolic intermediates, and valuable
      end-products derived from lignocellulose bioprocessing. 

PMID- 24743030
TI  - Working for food you don't desire. Cues interfere with goal-directed food
      seeking.
AB  - Why do we indulge in food-seeking and eating behaviors at times when we are
      already fully sated? In the present study we investigated the hypothesis that
      food-associated cues in the environment can interfere with goal-directed action
      by eliciting food-seeking that is independent of the current desirability of the
      outcome. To this end, we used a computerized task in which participants learned
      to press keys for chocolate and popcorn rewards. Subsequently, we investigated
      whether satiation on one of these rewards would bias choice toward the other,
      still desirable, food reward. We found that satiation did indeed selectively
      reduce responding on the associated key in the absence of food-associated cues.
      In contrast, in a Pavlovian-instrumental transfer (PIT) test, satiation failed to
      reduce cue-elicited food-seeking: in line with our hypothesis, cues that had
      previously been paired with chocolate and popcorn led to increased responding for
      the signaled food reward, independent of satiation. Furthermore, we show that
      food-associated cues will not only bias choice toward the signaled food (outcome
      specific transfer), but also enhance the vigor of responding generally (general
      transfer). These findings point to a mechanism that may underlie the powerful
      control that cues in our obesogenic environment exert over our behavior. 

PMID- 24743029
TI  - Effects of ceftriaxone on systemic and central expression of anti- and pro
      inflammatory cytokines in alcohol-preferring (P) rats exposed to ethanol.
AB  - AIMS: Determine the effect of reduction in ethanol consumption by alcohol
      preferring (P) rats, following ceftriaxone treatment, on the cytokines levels in
      prefrontal cortex (PFC) and plasma. METHODS: Following 5 weeks of free access to
      ethanol (15 and 30%), P rats were treated daily with ceftriaxone or saline
      vehicle for either 2 or 5 consecutive days. Plasma and PFC were collected from
      ceftriaxone- and saline vehicle-treated groups, and assayed for the levels of pro
      and anti-inflammatory cytokines. RESULTS: A significant increase in the plasma
      level of anti-inflammatory cytokine IL-10 was observed in the ceftriaxone-treated
      group when compared with the saline-treated group in both the 2-day and 5-day
      treatments. Furthermore, ceftriaxone treatment for 2 days induced reduction in
      TNFalpha level in both plasma and PFC. Additionally, ceftriaxone treatment for 2
      days significantly reduced the IFNgamma level in PFC. CONCLUSION: These findings
      show the ability of ceftriaxone to reduce alcohol consumption and induce
      modulation of the anti-inflammatory and pro-inflammatory cytokines levels in P
      rats.

PMID- 24743024
TI  - Pathways and therapeutic targets in melanoma.
AB  - This review aims to summarize the current knowledge of molecular pathways and
      their clinical relevance in melanoma. Metastatic melanoma was a grim diagnosis,
      but in recent years tremendous advances have been made in treatments.
      Chemotherapy provided little benefit in these patients, but development of
      targeted and new immune approaches made radical changes in prognosis. This would
      not have happened without remarkable advances in understanding the biology of
      disease and tremendous progress in the genomic (and other "omics") scale analyses
      of tumors. The big problems facing the field are no longer focused exclusively on
      the development of new treatment modalities, though this is a very busy area of
      clinical research. The focus shifted now to understanding and overcoming
      resistance to targeted therapies, and understanding the underlying causes of the
      heterogeneous responses to immune therapy. 

PMID- 24743031
TI  - The impact of a chlorotoxin-modified liposome system on receptor MMP-2 and the
      receptor-associated protein ClC-3.
AB  - Currently, it is unknown whether a receptor-associated protein will be affected
      when a ligand modified delivery system interacts with its receptor. Besides,
      chlorotoxin (ClTx)-modified liposomes can target to glioma cells, but the target
      molecule is not clear: MMP-2, ClC-3 or both? Here a comparative study of ClTx
      conjugated liposomes was conducted on two types of tumor cells: U87, a human
      glioma cell line with high expression of both MMP-2 and ClC-3, and A549, a human
      lung cancer cell line with expression of only MMP-2. ClTx-modified liposomes
      behaved similarly in these two cancer cells in terms of in vitro cell uptake,
      endocytosis pathway, intracellular trafficking and in vivo targeting efficacy,
      though the two tested cell lines were very different in ClC-3 expression. These
      results revealed that the targeted delivery of ClTx modified liposomes to U87
      tumor was MMP-2-mediated and not correlated with the chloride channel ClC-3. On
      the other hand, ClTx modified on the liposomes did activate the receptor
      associated protein ClC-3 via the binding with MMP-2, leading to the inhibition on
      cell migration and chloride currents. This is significant because cell migration
      is a key step in tumor metastasis. Interestingly, higher in vitro cellular uptake
      and lower in vivo tumor accumulation of liposomal systems was found in U87
      compared to the A549 model, possibly due to the biological differences between in
      vitro and in vivo models. In general, ClTx-modified delivery systems may
      potentially target to tumors other than glioma that express a high level of MMP
      2, and its effect on ClC-3 may help prevent tumor metastasis. 

PMID- 24743032
TI  - A polycaprolactone-tricalcium phosphate composite scaffold as an autograft-free
      spinal fusion cage in a sheep model.
AB  - Titanium (Ti) based spinal fusion cages are frequently used in the clinics for
      the treatment of spinal degeneration and related diseases, however, their further
      clinical application is generally harassed by several drawbacks such as stress
      shielding, non-biodegradability and additional bone grafting procedure. Our
      earlier work has demonstrated the efficacy of a biodegradable macro-porous
      polycaprolactone-tricalcium phosphate (PCL-TCP) composite scaffold in promoting
      bony tissue ingrowth as well as its ability to sustain mechanical loads upon
      implantation into an orthotopic defect site. In this study, we investigated the
      use of PCL-TCP scaffold as an autograft-free spinal fusion cage in a preclinical
      sheep model over 12 months, and compared the fusion efficacy against Ti cages
      incorporated with autografts. Results showed that despite PCL-TCP scaffold as an
      autograft-free cage attaining a slower fusion rate at early stage (6 month), it
      achieved similar degree of spinal fusion efficacy as Ti cages aided with
      autograft at 12 month post-operation as evidenced by the radiographic and
      histological evaluation. PCL-TCP cages alone demonstrated better bone ingrowth
      with 2.6 fold higher bone/interspace ratio (B/I) and more homogeneous bone tissue
      distribution compared with that of the Ti cages (88.10  +/-  3.63% vs. 33.74  +/-
      2.78%, p < 0.05) as seen from the histological and micro-CT analysis. Moreover,
      besides the bone tissue ingrowth, a quantitative approach was illustrated to
      accurately evaluate the osteointegration of fusion cage with surrounding bone
      tissue, and showed a 1.36 fold higher degree of osteointegration occurred in PCL
      TCP cage group than Ti cage group (CS/PC: 79.31  +/-  3.15% vs 58.44  +/-  2.43%,
      p < 0.05). Furthermore, biomechanical analysis showed comparable mechanical
      strength of fused segments in both groups in terms of the range of motion and
      stiffness at 12 month (p > 0.05). The degradation profile of the PCL-TCP cages
      was noted to increase in tandem with new bone ingrowth into the pores, while
      maintaining good structural integrity necessary for supporting the spinal
      interbody segments. Therefore, with the better osteointegration, more bone tissue
      ingrowth as well as its favorable biodegradable and radiolucent properties, PCL
      TCP cage has been demonstrated to be a promising candidate as an autograft-free
      fusion cage for clinical application. 

PMID- 24743033
TI  - Nanoparticles functionalized with Pep-1 as potential glioma targeting delivery
      system via interleukin 13 receptor alpha2-mediated endocytosis.
AB  - The treatment for glioma is one of the most challenging problems and therapeutic
      effect of glioma is often limited due to poor penetration into the tumor tissue.
      Interleukin 13 receptor alpha2 (IL-13Ralpha2) is over-expressed on tumor
      including established glioma cell lines and primary glioblastoma cell cultures.
      However, it will not cause activation of its signaling pathways. So it could be
      served as a promising targeted moiety for anti-glioma drug delivery. Pep-1, one
      specific ligand of IL-13Ralpha2, was identified to exhibit excellent capacity of
      crossing the blood tumor barrier (BTB) and homing to giloma. In this study, based
      on the IL-13Ralpha2-mediated endocytosis, Pep-1 was exploited as a potential
      ligand for effective glioma-targeting delivery. Pep-1 was functionalized to the
      surface of PEG-PLGA nanoparticles (Pep-NP) to evaluate its glioma homing, by
      taking advantage of the excessive expression of the IL-13Ralpha2 on the surface
      of glioma cells. Compared with non-targeting nanoparticles, Pep-NP exhibited a
      significantly enhanced cellular association in rat C6 glioma cells and improved
      penetration in 3D avascular C6 glioma spheroids. Following intravenous
      administration, Pep-NP could facilitate the distribution of the coumarin-6 in
      vivo glioma region, 2.21 times higher than that of NP for quantitative analysis.
      In conclusion, the Pep-NP could precisely target to the brain glioma, which was a
      potential targeting drug delivery system for glioma treatment. 

PMID- 24743034
TI  - [Pseudoexfoliation syndrome and phacoemulsification: a comparative study with a
      control population].

PMID- 24743035
TI  - [Ethmoid esthesioneuroblastoma presenting with ophthalmologic manifestations].

PMID- 24743036
TI  - The BCS annual conference, Manchester, 2-4 June 2014: the vice-president's
      message.

PMID- 24743038
TI  - Interactions between inflammatory activation and endothelial dysfunction
      selectively modulate valve disease progression in patients with bicuspid aortic
      valve.
AB  - OBJECTIVES: Bicuspid aortic valve (BAV) is associated with increased risk of
      valvular degeneration and ascending aortic aneurysm formation and rupture. We
      sought to evaluate the roles of endothelial dysfunction and inflammatory
      activation in modulating these processes. METHODS: We performed a case-control
      study of patients with BAV together with a multivariate analysis within the BAV
      group to identify factors associated with: development of significant valvular
      disease; dilatation of the ascending aorta; differential valve relative to aortic
      disease. Endothelial function of patients and controls was evaluated via flow
      mediated dilatation (FMD) and plasma concentrations of asymmetric
      dimethylarginine (ADMA). Correlations with inflammatory markers and endothelial
      progenitor cell counts were also examined. Morphological and physiological
      assessment of the valve and ascending aorta was performed with transthoracic
      echocardiography and MRI. RESULTS: Patients with BAV (n=43) and controls (n=25)
      were matched for age and gender. FMD was significantly lower in patients than
      controls (7.85+/-3.48% vs 11.58+/-3.98%, p=0.001), and these differences were age
      independent. Within the BAV cohort, multivariate correlates of peak aortic valve
      velocity were plasma concentrations of ADMA and myeloperoxidase (MPO) (both
      p<0.01), while increasing age was an independent correlate of ascending aortic
      diameter (p<0.05). Furthermore, both low FMD and inflammatory activation were
      multivariate correlates of selectivity for valvular disease. CONCLUSIONS: BAV is
      associated with endothelial dysfunction. The extent of inflammatory activation
      (specifically MPO release) and that of endothelial dysfunction impact primarily
      on integrity of the valve rather than aortic structure.

PMID- 24743039
TI  - Pulsatile high-velocity turbulent flow in lower extremity venous ultrasonography.
      Displaced venous valve.

PMID- 24743040
TI  - In-vivo dosimetry for field sizes down to 6 * 6 mm2 in shaped beam radiosurgery
      with microMOSFET.
AB  - The aim of this study is to evaluate microMOSFET as in-vivo dosimeter in 6 MV
      shaped-beam radiosurgery for field sizes down to 6 * 6 mm2. A homemade build-up
      cap was developed and its use with microMOSFET was evaluated down to 6 * 6 mm2.
      The study with the homemade build-up cap was performed considering its influence
      on field size over-cover occurring at surface, achievement of the overall process
      of electronic equilibrium, dose deposition along beam axis and dose attenuation.
      An optimized calibration method has been validated using MOSFET in shaped-beam
      radiosurgery for field sizes from 98 * 98 down to 18 * 18 mm2. The method was
      detailed in a previous study and validated in irregular field shapes series
      measurements performed on a head phantom. The optimized calibration method was
      applied to microMOSFET equipped with homemade build-up cap down to 6 * 6 mm2.
      Using the same irregular field shapes, dose measurements were performed on head
      phantom. MicroMOSFET results were compared to previous MOSFET ones. Additional
      irregular field shapes down to 8.8 * 8.8 mm2 were studied with microMOSFET.
      Isocenter dose attenuation due to the homemade build-up cap over the microMOSFET
      was near 2% irrespective of field size. Our results suggested that microMOSFET
      equipped with homemade build-up cap is suitable for in-vivo dosimetry in shaped
      beam radiosurgery for field sizes down to 6 * 6 mm2 and therefore that the
      required build-up cap dimensions to perform entrance in-vivo dosimetry in small
      fields have to ensure only partial charge particle equilibrium.

PMID- 24743041
TI  - Rapid response team implementation and in-hospital mortality*.
AB  - OBJECTIVE: To determine the relationship between implementation of rapid response
      teams and improved mortality rate using a large, uniform dataset from one state
      in the United States. DESIGN: This observational cohort study included 471,062
      adult patients hospitalized between 2001 and 2009. SETTING: Ten acute tertiary
      care hospitals in Washington State. PATIENTS OR OTHER PARTICIPANTS: Hospital
      abstract records on adult patients (18 years old or older) were examined (n =
      471,062). Patients most likely to benefit from rapid response team interventions
      were included and other prognostic factors of severity of illness and
      comorbidities were controlled. Each participating hospital provided the
      implementation date of their rapid response team intervention. Mortality rates in
      31 months before rapid response team implementation (pre-rapid response team time
      period) were compared with mortality rates in 31 months following rapid response
      team implementation (post-rapid response team time period). INTERVENTION(S):
      Implementation of a rapid response team within each acute tertiary care hospital.
      MEASUREMENTS AND MAIN RESULTS: In-hospital mortality. Relative risk for in
      hospital mortality improved in the post-rapid response team time period compared
      with the pre-rapid response team time period (relative risk = 0.76; 95% CI = 0.72
      0.80; p < 0.001). CONCLUSIONS: In-hospital mortality improved in six of 10 acute
      tertiary care hospitals in the post-rapid response team time period when compared
      with the pre-rapid response team time period. Because of a long-term trend of
      decline in hospital mortality, these decreases could not be unambiguously
      attributed to rapid response team implementation. Further research should examine
      additional objective outcomes and optimal configuration of rapid response teams
      to maximize intervention effectiveness.

PMID- 24743042
TI  - Mechanical ventilation-induced intrathoracic pressure distribution and heart-lung
      interactions*.
AB  - OBJECTIVE: Mechanical ventilation causes cyclic changes in the heart's preload
      and afterload, thereby influencing the circulation. However, our understanding of
      the exact physiology of this cardiopulmonary interaction is limited. We aimed to
      thoroughly determine airway pressure distribution, how this is influenced by
      tidal volume and chest compliance, and its interaction with the circulation in
      humans during mechanical ventilation. DESIGN: Intervention study. SETTING: ICU of
      a university hospital. PATIENTS: Twenty mechanically ventilated patients
      following coronary artery bypass grafting surgery. INTERVENTION: Patients were
      monitored during controlled mechanical ventilation at tidal volumes of 4, 6, 8,
      and 10 mL/kg with normal and decreased chest compliance (by elastic binding of
      the thorax). MEASUREMENTS AND MAIN RESULTS: Central venous pressure, airway
      pressure, pericardial pressure, and pleural pressure; pulse pressure variations,
      systolic pressure variations, and stroke volume variations; and cardiac output
      were obtained during controlled mechanical ventilation at tidal volume of 4, 6,
      8, and 10 mL/kg with normal and decreased chest compliance. With increasing tidal
      volume (4, 6, 8, and 10 mL/kg), the change in intrathoracic pressures increased
      linearly with 0.9 +/- 0.2, 0.5 +/- 0.3, 0.3 +/- 0.1, and 0.3 +/- 0.1 mm Hg/mL/kg
      for airway pressure, pleural pressure, pericardial pressure, and central venous
      pressure, respectively. At 8 mL/kg, a decrease in chest compliance (from 0.12 +/-
      0.07 to 0.09 +/- 0.03 L/cm H2O) resulted in an increase in change in airway
      pressure, change in pleural pressure, change in pericardial pressure, and change
      in central venous pressure of 1.1 +/- 0.7, 1.1 +/- 0.8, 0.7 +/- 0.4, and 0.8 +/-
      0.4 mm Hg, respectively. Furthermore, increased tidal volume and decreased chest
      compliance decreased stroke volume and increased arterial pressure variations.
      Transmural pressure of the superior vena cava decreased during inspiration,
      whereas the transmural pressure of the right atrium did not change. CONCLUSIONS:
      Increased tidal volume and decreased chest wall compliance both increase the
      change in intrathoracic pressures and the value of the dynamic indices during
      mechanical ventilation. Additionally, the transmural pressure of the vena cava is
      decreased, whereas the transmural pressure of the right atrium is not changed.

PMID- 24743043
TI  - Mix and match of KPC-2 encoding plasmids in Enterobacteriaceae-comparative
      genomics.
AB  - We performed comparative sequence analysis of 3 blaKPC-2 encoding plasmids to
      examine evolution of these plasmids and their dissemination. We found that all of
      them have an IncN replicon with a newly determined IncN plasmid sequence type
      (ST), ST15. The 2 Klebsiella pneumoniae (KPN) plasmids also harbor an IncF2A1-B1-
      replicon. The blaKPC-2 is located in the Tn4401c transposon with a newly
      discovered mutation in the P2 promoter. Screening of the 27 additional blaKPC-2
      carrying plasmids from Enterobacter cloacae, Escherichia coli (EC), and K.
      pneumoniae showed that: all KPN and EC plasmids are IncN plasmids belonging to
      ST15; 4/7 KPN and 1/6 EC plasmids contain an additional IncF2A1-B1- replicon; all
      Enterobacter plasmids belong to neither IncN nor IncF2A1-B1- replicon plasmids;
      6/7 KPN and 2/5 EC plasmids carry the mutated P2 promoter. Study of the blaKPC-2
      environment, transposon, pMLST, and Inc group suggests transposon and plasmid
      inter- and intra-species dissemination and evolution. 

PMID- 24743045
TI  - A novel phosphorus repletion strategy in a patient with duodenal perforation.
AB  - We describe a case in which a patient receiving parenteral nutrition (PN)
      developed hypophosphatemia. Due to lack of availability of parenteral phosphate
      supplements, we chose to restore phosphate using diluted hypertonic sodium
      phosphate enemas. Due to the recent shortages of parenteral minerals and
      vitamins, such an alternate means of repletion is of increasing importance.
      Diluted hypertonic sodium phosphate enemas are inexpensive, easy to administer,
      and effective since phosphate is readily absorbed across the rectal mucosa. We
      hope that through this type of repletion, life-threatening hypophosphatemia among
      patients receiving PN can be avoided. 

PMID- 24743044
TI  - Novel downstream molecular targets of SIRT1 in melanoma: a quantitative
      proteomics approach.
AB  - Melanoma is one of the most lethal forms of skin cancer and its incidence is
      continuing to rise in the United States. Therefore, novel mechanism and target
      based strategies are needed for the management of this disease. SIRT1, a NAD(+)
      dependent class III histone deacetylase, has been implicated in a variety of
      physiological processes and pathological conditions. We recently demonstrated
      that SIRT1 is upregulated in melanoma and its inhibition by a small-molecule,
      tenovin-1, inhibits cell proliferation and clonogenic survival of melanoma cells,
      possibly via activating p53. Here, we employed a gel free quantitative proteomics
      approach to identify the downstream effectors and targets of SIRT1 in melanoma.
      The human malignant melanoma, G361 cells were treated with tenovin-1 followed by
      protein extraction, in liquid trypsin digestion, and peptide analyses using
      nanoLC-MS/MS. A total of 1091 proteins were identified, of which 20 proteins
      showed significant differential expression with 95% confidence interval. These
      proteins were subjected to gene ontology and Ingenuity Pathway Analysis (IPA) to
      obtain the information regarding their biological and molecular functions. Real
      Time qRT-PCR validation showed that five of these (PSAP, MYO1B, MOCOS, HIS1H4A
      and BUB3) were differentially expressed at mRNA levels. Based on their important
      role in cell cycle regulation, we selected to focus on BUB family proteins (BUB3,
      as well as BUB1 and BUBR1) for subsequent validation. The qRT-PCR and immunoblot
      analyses showed that tenovin-1 inhibition of SIRT1 resulted in a downregulation
      of BUB3, BUB1 and BUBR1 in multiple melanoma cell lines. Since tenovin-1 is an
      inhibitor of both SIRT1 and SIRT2, we employed lentivirus mediated silencing of
      SIRT1 and SIRT2 in G361 cells to determine if the observed effects on BUB family
      proteins are due to SIRT1- or SIRT2- inhibition. We found that only SIRT1
      inhibition resulted in a decrease in BUB3, BUB1 and BUBR1. Our study identified
      the mitotic checkpoint regulator BUB family proteins as novel downstream targets
      of SIRT1. However, further validation is needed in appropriate models to confirm
      our findings and expand on our observations. 

PMID- 24743046
TI  - An overview of the diagnosis and management of nutrition in chronic pancreatitis.
AB  - Chronic pancreatitis is characterized by long-standing inflammation of the
      pancreas, which results in fibrosis and the gradual loss of pancreatic function.
      The loss of islets and acinar cells results in diabetes and exocrine
      insufficiency, respectively. Exocrine insufficiency can result in maldigestion of
      fat, protein, and carbohydrate as well as vitamins and minerals. Patients may
      present with variable severity of disease, from mild to severe. The diagnosis of
      chronic pancreatitis can be challenging, especially in patients with early or
      mild disease who have few to no morphologic abnormalities on standard abdominal
      imaging studies. A number of imaging modalities and tests have evolved to aid in
      the diagnosis of chronic pancreatitis based on changes in structure or function.
      Clinicians typically focus on treating pain in chronic pancreatitis as opposed to
      exocrine insufficiency, despite the fact that maldigestion and malabsorption can
      result in nutrition deficiencies. The aims of this review are to describe the
      various modalities used to diagnose chronic pancreatitis, to illustrate the
      nutrition deficiencies associated with exocrine insufficiency, and to provide an
      overview of nutrition assessment and treatment in these patients. 

PMID- 24743047
TI  - Relationship Between Fat-Soluble Vitamin Supplementation and Blood Concentrations
      in Adolescent and Adult Patients With Cystic Fibrosis.
AB  - Background: Pancreatic insufficiency is common in patients with cystic fibrosis
      (CF) and leads to malabsorption of fat-soluble vitamins. Multivitamins, including
      vitamins A, D, E, and K, are routinely prescribed to patients with CF to prevent
      vitamin deficiencies. Our objective was to examine the relationship between fat
      soluble vitamin supplements and their impact on blood concentrations. Methods:
      This was a retrospective chart review of patients with CF who were treated at
      Emory Clinic and Emory University Hospital during 2008-2012. The amount of fat
      soluble vitamin supplementation, serum markers of fat-soluble vitamin
      concentrations, CF transmembrane conductance regulator genotype, and other
      demographic information were recorded from electronic medical records. Mixed
      effects models were used to investigate the trends over time of fat-soluble
      vitamin supplements and serum vitamin concentrations. Results: In total, 177
      charts were eligible. Mean (SD) age was 26.1 (10.2) years. Ninety-two percent of
      patients had pancreatic insufficiency and 52% had the homozygous DeltaF508
      mutation. Recorded fat-soluble vitamin supplementation increased in the past 5
      years (P < .001 for all). Serum 25-hydroxyvitamin D increased slightly (3%
      increase; P < .01); however, there were no changes in the blood concentrations of
      vitamins A, E, and K (P = .26-.96). Conclusions: Despite a near doubling of
      recorded fat-soluble vitamin supplementation over the past 5 years, there was no
      parallel increase in blood concentrations of these vitamins. Potential reasons
      include suboptimal dosages, low adherence, or ongoing issues with malabsorption.

PMID- 24743048
TI  - Inter-method variability in bone alkaline phosphatase measurement: clinical
      impact on the management of dialysis patients.
AB  - BACKGROUND: Bone-specific alkaline phosphatase (BAP) is now recommended to assess
      bone turnover in hemodialysis (HD) patients. However, little is known about
      potential variability between methods available to measure BAP. METHODS: We
      measured BAP in 76 HD patients with six different assays (Beckman-Coulter Ostase
      IRMA, Beckman-Coulter Ostase Access, IDS iSYS Ostase, IDS Ostase enzyme
      immunoassay, DiaSorin Liaison Ostase and Quidel MicroVue BAP). RESULTS: We
      observed a high correlation between all the assays ranging from 0.9948 (IDS iSYS
      vs. IDS EIA) to 0.9215 (DiaSorin Liaison vs. Quidel MicroVue). However, using the
      regression equations, the equivalent concentration of a Beckman-Coulter Access
      value of 10 MUg/L can range from 7.7 to 14.4 MUg/L and of 20 MUg/L can range from
      16.9 to 27.9 MUg/L with other assays. According to Beckman-Coulter Access, 13%,
      50% and 37% of the patients presented BAP values <=10, between 10 and 20 and >=20
      MUg/L, respectively. Discrepancies are observed when other assays are used
      (concordance from 10 to 100%). CONCLUSIONS: Analytical problems leading to inter
      method variation should be overcome to improve the usefulness of this marker in
      clinical practice. According to correlation results, recalibration of BAP assays
      is necessary but should not be a major issue.

PMID- 24743049
TI  - Multicentre evaluation of glycated haemoglobin (HbA1c) of Roche Diagnostics in
      Andalusia.
AB  - BACKGROUND: A Spanish multicentre evaluation of the third generation of Roche
      Diagnostics immunoturbidimetric inhibition method (TINIA) is presented for
      quantification of haemoglobin A1c (HbA1c) in whole blood. METHODS: The analytical
      performance of the TINIA test was evaluated and blood sample results were
      compared with two other widely used analysers, Bio-Rad Variant II and Adams
      Arkray HA-8160, based on HPLC. RESULTS: Within- and between-batch imprecision
      (coefficients of variation (CVs)) for HbA1c levels of 5, 6, 7 and 8% were 0.77,
      1.23, 1.35 and 1.26% and 2.38, 1.51, 1.76 and 2.16%, respectively. For low (5.4%
      A1c) and high (10.1% A1c) quality control samples, the within and between-batch
      %CV were: 1.26; 1.43 and 2; 1.71 respectively. The test met the expected
      performance in most aspects, except for linearity, that is under the reported
      range, and HbF interferences, detected for levels over 7.5%. There was a good
      concordance between the results of TINIA and Variant-IIt in the whole range and
      with HA-8160 only up to levels of 9%. Between-batch imprecision suggests more
      frequent calibrations than reported by the provider to maintain variability
      within the limits established by clinical practice guidelines. CONCLUSIONS: The
      assay meets the necessary quality standards for routine use, as long as we keep
      the analytical variability within narrow limits. The results may be
      interchangeable with the tested HPLC systems, but HbF interference is not
      detected and it happens at lower levels than reported.

PMID- 24743050
TI  - Nativity and serum concentrations of antioxidants in Mexican American children: a
      cross-sectional study.
AB  - There is limited research on the effect of immigration on biological markers of
      nutrition among children of Mexican origin in the United States. The purpose of
      this cross-sectional study was to examine data from the Third National Health and
      Nutrition Examination Survey (NHANES III) (1988-1994), on a national and
      representative sample of 1559 Mexican American children, 4-16 years of age, and
      assess the associations of country of birth with serum concentrations of
      carotenoids, vitamin A, and vitamin E. In multiple regression analyses, Mexico
      born Mexican American children had significantly higher serum concentrations of
      alpha-carotene, beta-carotene, beta-cryptoxanthin, lutein/zeaxanthin, vitamin A,
      and vitamin E than their counterparts who were born in the United States after
      adjustment for age, sex, poverty income ratio, level of education of family
      reference person, body mass index, total serum cholesterol, serum cotinine, total
      energy intake, and vitamin/mineral consumption. Our findings confirm evidence for
      a negative effect of immigration/acculturation on dietary quality in this
      population. These findings also suggest that immigrant Mexican families should be
      encouraged to maintain their consumption of fruits and vegetables. Prospective
      studies are needed to further assess the effects of immigration/acculturation on
      diet and other health outcomes in children of Mexican origin and immigrants. 

PMID- 24743051
TI  - Radiation recall dermatitis and radiation pneumonitis during treatment with
      vemurafenib.
AB  - The basis of radiation recall reactions (RRR) is a subclinical radiation damage
      that is uncovered later by treatment with anticancer agents. Several drugs have
      been associated with RRR, in particular taxanes and anthracyclines. Recently, a
      few cases were reported concerning radiation recall dermatitis caused by
      vemurafenib. Up to now, there have been no reports of RRR in the lung induced by
      vemurafenib. We describe the occurrence of RRR in three melanoma patients who had
      undergone radiotherapy for metastases followed by systemic treatment with the
      BRAF inhibitor vemurafenib. Two patients developed radiation recall pneumonitis
      (RRP) and one patient developed radiation recall dermatitis (RRD) 5-7 weeks after
      the radiation treatment was finished and 2-4 weeks after vemurafenib was started.
      The early application of systemic (RRP) and topical corticosteroids (RRD) enabled
      us to continue the treatment with vemurafenib without dose reduction. Caution is
      needed when vemurafenib is planned for patients who have undergone previous
      radiotherapy, and RRR of the skin and the lung have to be taken into account. 

PMID- 24743053
TI  - Four cases of rituximab-associated melanoma.
AB  - Biological agents have transformed the management of inflammatory and
      proliferative disorders. Safety issues have been raised, particularly the
      increased risk of opportunistic infections and secondary cancers. We report four
      cases of melanoma worsening or occurring after rituximab treatment for associated
      B-cell lymphoma, and discuss the accountability of the molecule in this process.
      In three cases, melanoma was diagnosed before or at the same time as a B-cell
      lymphoma treated with rituximab associated with chemotherapy and we observed
      rapid metastatic progression. In the last case, melanoma appeared after 5 years
      treatment with rituximab for a follicular lymphoma. Although it is premature to
      conclude on the role of rituximab in melanoma, careful follow-up and registration
      of such cases are important to gain further insight on this topic. 

PMID- 24743052
TI  - Phase I trial of biochemotherapy with cisplatin, temozolomide, and dose
      escalation of nab-paclitaxel combined with interleukin-2 and interferon-alpha in
      patients with metastatic melanoma.
AB  - The primary objective of this study was to determine the safety, toxicity, and
      maximum tolerated dose of nanoparticle albumin-bound (nab)-paclitaxel as part of
      biochemotherapy for metastatic melanoma and to determine whether substituting nab
      paclitaxel for less potent agents could increase response rates and duration.
      Treatment consisted of intravenous cisplatin (20 mg/m) on days 1-4, oral
      temozolomide (250 mg/m) on days 1-3, subcutaneous interferon-alpha (5*10 IU/m) on
      days 1-5, and continuous intravenous interleukin-2 (9*10 IU/m) for 96 h on days 1
      4. A standard 3+3 dose escalation method was used; the nab-paclitaxel starting
      dose was 100 mg/m on day 1 and 70 mg/m on day 5. The treatment cycle was repeated
      every 3 weeks and toxicity was assessed weekly. Ten patients were enrolled. Dose
      limiting toxicities included diarrhea, transaminasemia, and neutropenia. The
      maximum tolerated dose was not identified because the nab-paclitaxel dose on day
      1 at the lowest planned dose (80 mg/m) caused dose-limiting toxicity in two of
      five patients. Of the nine patients who were evaluable for response, five had a
      partial response. The median time to disease progression was 5.30 months and the
      median overall survival was 8.73 months. Six patients developed central nervous
      system metastasis at a median of 5.33 months after treatment initiation.
      Biochemotherapy including nab-paclitaxel according to the doses and schedule
      regimen used in the present study has significant toxicity. Substituting
      dacarbazine with temozolomide did not prevent central nervous system metastasis
      in patients with metastatic melanoma. 

PMID- 24743054
TI  - Akt and PI3K-dependent but CREB-independent upregulation of MCAM by endothelin-3
      in human melanocytes.
AB  - Melanoma cell adhesion molecule (MCAM) is upregulated during melanoma
      progression, and associated with invasion and metastasis. Little is known about
      the factors that regulate MCAM expression in vivo. Mutations that upregulate MCAM
      have not been found, and AKT activating mutations are rare in melanomas. This
      suggests that an epigenetic factor may be responsible for upregulating MCAM and
      activating AKT in vivo. Although endothelin-1 and endothelin-3 (ET-1, ET-3) are
      physiologically relevant factors capable of upregulating MCAM in melanocytic
      cells, a mechanism of action has never been established. Here we show that
      pharmacologic inhibition of map kinase kinase (MEK) or phosphoinositol 3 kinase
      (PI3K) blocks MCAM upregulation by ET-3, implicating MEK and PI3K/Akt kinases in
      ET-3 regulation of MCAM. Despite the fact that there are cAMP response element
      binding protein (CREB) sites in the MCAM promoter, suppression of CREB expression
      by siRNA silencing does not block ET-3 mediated upregulation of MCAM. Rather, ET
      3 stimulation of melanocytes promotes Akt phosphorylation at Ser 473, which is
      suppressed by PI3K inhibition or silencing of Akt, in turn blocking ET-3
      upregulation of MCAM. We conclude therefore that ETs upregulate MCAM in an Akt
      and ERK/MEK-dependent, but CREB-independent manner, providing an understanding
      for possible pharmacologic intervention in progressing melanoma. 

PMID- 24743055
TI  - Comparative proteomic analysis reveals unique tumor protein composition among the
      melanoma subtypes pure desmoplastic and superficial spreading.
AB  - The U.S. death rate for melanoma has not decreased, despite the use of depth at
      biopsy and sentinel lymph node status to determine the risk of metastasis.
      Additional prognostic indicators and therapeutic targets are required, and
      identification of candidate proteins was the goal of this study. We utilized
      comparative mass spectrometry to compare five samples of each of two forms of
      melanoma, pure desmoplastic, which by depth at diagnosis has a favorable
      prognosis, and superficial spreading. Ontological analysis was applied to
      identify proteins and networks that were increased in one of the two subtypes.
      Analysis revealed a protein signature increase in pure desmoplastic melanoma
      associated with cell-to-cell binding and a signature increase in superficial
      spreading melanoma responsible for the cellular stress response including a
      constellation of heat shock proteins. The two subtypes of melanoma compared in
      this study have two unique protein compositions that correlate with their
      phenotypes. Further validation studies are warranted to evaluate the utility of
      identified proteins as prognostic markers and therapeutic targets.

PMID- 24743056
TI  - Evaluation of the Wharton's jelly poroelastic parameters through compressive
      tests on placental and foetal ends of human umbilical cords.
AB  - The umbilical cord is a conduit between the developing foetus and the placenta.
      In physiological conditions it contains two arteries and one vein immersed in a
      mucoid tissue called Wharton's jelly. Although the extreme importance of such a
      structure is fully recognized, the umbilical cord and its components have been
      scarcely studied. A deep investigation on the biomechanics of the umbilical cord
      could help to understand if the pregnancy outcome is influenced by umbilical cord
      mechanical properties, however, detailed biomechanical data are still lacking. In
      the present study, the mechanical properties during compression of the human
      Wharton's jelly have been evaluated using a poroelastic approach. Multi-ramp
      stress-relaxation tests in both confined and unconfined configurations were
      performed on Wharton's jelly samples extracted from foetal and placental sides of
      twenty human umbilical cords. The Young modulus and Aggregate modulus were
      calculated at three strain levels and the hydraulic permeability was found by
      fitting the confined stress-relaxation data to the analytical solution and
      minimizing the stress least square differences. The Wharton's jelly exhibits a
      highly non linear and viscoelastic behaviour showing a dependence on the applied
      strain values and a ~90% and ~85% relaxation in unconfined and confined
      configuration, respectively. Moreover, equilibrium Young and Aggregate moduli
      resulted significantly higher and the permeability significantly lower at the
      foetal than the placental site, showing a dependence of the three material
      parameters on the location (foetal or placental) and, consequently, a non
      homogeneity in the Wharton's jelly mechanical properties. 

PMID- 24743057
TI  - Platinum metallization for MEMS application: focus on coating adhesion for
      biomedical applications.
AB  - The adherence of Platinum thin film on Si/SiO 2 wafer was studies using Chromium,
      Titanium or Alumina (Cr, Ti, Al 2O 3) as interlayer. The adhesion of Pt is a
      fundamental property in different areas, for example in MEMS devices, which
      operate at high temperature conditions, as well as in biomedical applications,
      where the problem of adhesion of a Pt film to the substrate is known as a major
      challenge in several industrial applications health and in biomedical devices,
      such as for example in the stents. (1)(-) (4) We investigated the properties of
      Chromium, Titanium, and Alumina (Cr, Ti, and Al 2O 3) used as adhesion layers of
      Platinum (Pt) electrode. Thin films of Chromium, Titanium and Alumina were
      deposited on Silicon/Silicon dioxide (Si/SiO 2) wafer by electron beam. We
      introduced Al 2O 3 as a new adhesion layer to test the behavior of the Pt film at
      higher temperature using a ceramic adhesion thin film. Electric behaviors were
      measured for different annealing temperatures to know the performance for Cr/Pt,
      Ti/Pt, and Al 2O 3/Pt metallic film in the gas sensor application. All these
      metal layers showed a good adhesion onto Si/SiO 2 and also good Au wire
      bondability at room temperature, but for higher temperature than 400  degrees C
      the thin Cr/Pt and Ti/Pt films showed poor adhesion due to the atomic inter
      diffusion between Platinum and the metal adhesion layers. (5) The proposed Al 2O
      3/Pt ceramic-metal layers confirmed a better adherence for the higher
      temperatures tested.

PMID- 24743058
TI  - Inhibition downunder: an update from the spinal cord.
AB  - Inhibitory neurons in the spinal cord perform dedicated roles in processing
      somatosensory information and shaping motor behaviors that range from simple
      protective reflexes to more complex motor tasks such as locomotion, reaching and
      grasping. Recent efforts examining inhibition in the spinal cord have been
      directed toward determining how inhibitory cell types are specified and
      incorporated into the sensorimotor circuitry, identifying and characterizing
      molecularly defined cohorts of inhibitory neurons and interrogating the
      functional contribution these cells make to sensory processing and motor
      behaviors. Rapid progress is being made on all these fronts, driven in large part
      by molecular genetic and optogenetic approaches that are being creatively
      combined with neuroanatomical, electrophysiological and behavioral techniques. 

PMID- 24743059
TI  - VMAT techniques for lymph node-positive left sided breast cancer.
AB  - PURPOSE: To investigate the plan quality of two different volumetric modulated
      arc therapy (VMAT) techniques for lymph node-positive left-sided breast cancer.
      METHODS: Two VMAT plans were generated for 10 lymph node-positive left-sided
      breast cancer patients: one plan using one single segment of a full rotation,
      typically an arc segment of 230 degrees  (1s-VMAT); and a second plan consisting
      of 2 small tangential arc segments of about 50 degrees  (2s-VMAT). For plan
      comparison, various dose and dose volume metrics (Dmean, D98%, D2% for target
      volumes, D2%, Dmean and Vx% for organs at risk (OAR)) were evaluated. RESULTS:
      Both techniques fulfilled both clinical target dose and OAR goals. 1s-VMAT
      achieved a slightly better homogeneity and better target coverage (D2%= 54.2 +/-
      0.7 Gy, D98%= 30.3 +/- 1.8 Gy) compared to 2s-VMAT (D2%= 55.0 +/- 1.1 Gy, D98%=
      29.9 +/- 1.7 Gy). For geometrical reasons, OAR sparing was noticeable but not
      significant better using 2s-VMAT, particularly heart and contralateral breast.
      The heart received a mean dose of 4.4 +/- 0.8 Gy using 1s-VMAT and 3.3 +/- 1.0 Gy
      using 2s-VMAT; the contralateral breast received 1.5 +/- 0.3 Gy and 0.9 +/- 0.3
      Gy, respectively. CONCLUSIONS: A VMAT technique based on two small tangential arc
      segments enables improved OAR sparing; the differences between the two techniques
      in target coverage and homogeneity are minor. Patient age and -anatomy must be
      considered for each individual case when deciding which technique to be used.

PMID- 24743060
TI  - Non-invasive multiparametric qBOLD approach for robust mapping of the oxygen
      extraction fraction.
AB  - INTRODUCTION: The quantitative blood oxygenation level-dependent (qBOLD) method
      has not become clinically established yet because long acquisition times are
      necessary to achieve an acceptable certainty of the parameter estimates. In this
      work, a non-invasive multiparametric (nimp) qBOLD approach based on a simple
      analytical model is proposed to facilitate robust oxygen extraction fraction
      (OEF) mapping within clinically acceptable acquisition times by using separate
      measurements. METHODS: The protocol consisted of a gradient-echo sampled spin
      echo sequence (GESSE), a T2-weighted Carr-Purcell-Meiboom-Gill (CPMG) sequence,
      and a T2(*)-weighted multi-slice multi-echo gradient echo (MMGE) sequence. The
      GESSE acquisition time was less than 5 minutes and the extra measurement time for
      CPMG/MMGE was below 2 minutes each. The proposed nimp-qBOLD approach was
      validated in healthy subjects (N = 5) and one patient. RESULTS: The proposed nimp
      qBOLD approach facilitated more robust OEF mapping with significantly reduced
      inter- and intra-subject variability compared to the standard qBOLD method.
      Thereby, an average OEF in all subjects of 27+/-2% in white matter (WM) and 29+/
      2% in gray matter (GM) using the nimp-qBOLD method was more stable compared to
      41+/-10% (WM) and 46+/-10% (GM) with standard qBOLD. Moreover, the spatial
      variance in the image slice (i.e. standard deviation divided by mean) was on
      average reduced from 35% to 25%. In addition, the preliminary results of the
      patient are encouraging. CONCLUSION: The proposed nimp-qBOLD technique provides a
      promising tool for robust OEF mapping within clinically acceptable acquisition
      times and could therefore provide an important contribution for analyzing tumors
      or monitoring the success of radio and chemo therapies.

PMID- 24743061
TI  - How often are interfacility transfers of spine injury patients truly necessary?
AB  - BACKGROUND CONTEXT: Traumatic spine injuries are often transferred to regional
      tertiary trauma centers from outside hospitals (OSHs) and subsequently discharged
      from the trauma center's emergency department (ED) suggesting secondary
      overtriage of such injuries. PURPOSE: The aim of the study was to investigate the
      definitive treatment and disposition of traumatic spine injuries transferred from
      OSH, particularly those without other trauma injuries or neurologic symptoms.
      STUDY DESIGN: This was a retrospective study. PATIENT SAMPLE: Adult patients
      presenting to a single Level 1 trauma center with spine injuries were included.
      OUTCOME MEASURES: The outcome measures considered in the study were
      appropriateness of transfer, treatment, and cost. METHODS: Four thousand five
      hundred consecutive adult patients presenting to a single Level 1 trauma center
      with spine injuries (isolated or polytrauma) were reviewed. This consisted of
      1,427 patients (32%) transferred from an OSH ED. All OSH, emergency medical
      services, and receiving institution (RI) patient records and imaging were
      reviewed. RESULTS: Patients who were neurologically intact, nonpolytrauma, and
      without critical medical issues at the OSH (isolated intact spine transfers)
      comprised 29% of transfers. Helicopters transported 13% of these patients. The
      most frequent injuries were compression (26%), burst (17%), and transverse
      process (10%) fractures. Seventy-eight percent were discharged directly from the
      RI's ED. Similarly, 15% were not given any formal treatment, 13% had surgery, and
      72% given orthosis treatment. The average cost for transportation and ED costs
      for those discharged from the RI ED were $1,863 and $12,895, respectively. Of the
      isolated intact spine transfers, 42% were considered to be inappropriate to
      warrant transfer. This was defined as those sent from an OSH with an orthopedic
      or neurosurgeon on staff and clearly stable injuries with minimal chance of
      progressing to instability. Isolated intact spine transfers whose OSH spine
      imaging was not considered unstable was 25% of transfers with a helicopter used
      to transport 14% of these patients. Eighty-seven percent were discharged from the
      ED, whereas only 3% went onto surgery. CONCLUSIONS: This study is the first to
      investigate interfacility transfers with spine injuries and found high rate of
      secondary overtriage of neurologically intact patients with isolated spine
      injuries. Potential solutions include increasing spine coverage in community EDs,
      increasing direct communication between the OSH and the spine specialist at the
      tertiary center, and utilization of teleradiology.

PMID- 24743062
TI  - Multiple somatic symptoms in employees participating in a randomized controlled
      trial associated with sickness absence because of nonspecific low back pain.
AB  - BACKGROUND CONTEXT: The prevalence of multiple somatic symptoms is high in
      primary and hospital outpatient populations. Multiple somatic symptoms may be
      present in patients sick-listed because of low back pain (LBP) and may be
      associated with increased risk of not returning to work (RTW). PURPOSE: To
      explore whether multiple somatic symptoms in a subset of patients with
      nonspecific LBP was associated with RTW, sickness absence (SA), or other social
      benefits. STUDY DESIGN: The study was a cohort study based on a randomized
      clinical trial with a prospective 2-year follow-up period. Patients were referred
      from general practices to the Spine Center, Regional Hospital Silkeborg, Denmark.
      PATIENT SAMPLE: Patients were 285 sick-listed employees (4-12 weeks), with
      nonspecific LBP as their prime reason for SA. Exclusion criteria were
      unemployment, radiculopathy, LBP surgery within the past year, previous lumbar
      fusion, suspected cauda equina syndrome, progressive paresis or other serious
      back disease, pregnancy, known substance abuse, or primary psychiatric diagnosis.
      OUTCOME MEASURES: Self-reported health was assessed by the LBP rating scale and
      questions about pain and health in general. Disabilities were measured by the
      Roland Morris Questionnaire, the Short Form-36, and the Fear-Avoidance Beliefs
      Questionnaire. Work-related questions comprised expectations about RTW and risk
      of losing job because of SA. The Common Mental Disorder Questionnaire (subscale
      SCL-SOM) was used to assess multiple somatic symptoms (12 items). We categorized
      multiple somatic symptoms into four groups based on the SCL-SOM sum score: <6, 6
      to 12, 13 to 18 and >18. Status of SA (>2 weeks) and RTW were gathered from a
      national database (DREAM). METHODS: The patients (N=285) were randomized into
      either multidisciplinary or brief intervention at the Spine Center (2004-2008).
      Both interventions comprised clinical examination and advice by a physiotherapist
      and a rheumatologist. Data were collected from questionnaires at baseline
      (inclusion) and 1 year after inclusion. Data on SA benefits were gathered from
      the DREAM database that contains data on all social transfer payments (such as
      sick leave benefits and other disability benefits) registered on a weekly basis.
      RESULTS: All health factors, female gender, and poor work ability were
      significantly associated with a higher level of multiple somatic symptoms. The
      percentage of persons with SA increased significantly with the symptom score
      after 1 year, and the duration of SA remained significantly longer after 2 years
      of follow-up between the multiple somatic symptoms groups. The percentages with
      RTW after 1 and 2 years were negatively associated with a higher level of
      multiple somatic symptoms at baseline. We found no difference between the
      intervention groups. CONCLUSIONS: A higher level of multiple somatic symptoms was
      significantly associated with poor health and work ability at baseline and with
      longer duration of SA and unsuccessful RTW through a 2-year follow-up period.

PMID- 24743063
TI  - Transient paresis in a congenital scoliosis with double rib protrusion into the
      spinal canal.

PMID- 24743064
TI  - Predicting epidural steroid injections with laboratory markers and imaging
      techniques.
AB  - BACKGROUND CONTEXT: Epidural steroid injections (ESIs) have been used for a
      number of years in the treatment of radicular pain caused by nerve root
      impingement or stenosis after failed conservative treatments with oral
      medications, physical therapy, and lifestyle modifications. PURPOSE: The purpose
      of this study was evaluation of predictive tools for ESI outcomes in treating
      radicular pain. STUDY DESIGN: This was a comprehensive, systematic review of the
      prognostic accuracy of certain predictive methods used to determine ESI outcomes.
      METHODS: Fifty articles were obtained via the PubMed database, using keywords and
      cross-referencing works cited. Inclusion criteria included patients with
      radicular pain, analysis of a specific prediction tool, and outcomes measured by
      improvement in pain and/or function. Exclusion criteria included literature
      review articles and animal or cadaver studies. Eight articles studying imaging
      techniques or laboratory markers as prediction tools underwent quality evaluation
      and evidence classification based on the 2011 American Academy of Neurology
      Clinical Practice Guideline Process Manual. RESULTS: For patients with radicular
      pain, there is insufficient evidence to either support or refute the prognostic
      accuracy of spinal stenosis seen on imaging in determining epidural steroid
      outcomes (two Class IV studies). It is possible that low-grade nerve root
      compression as seen on lumbar magnetic resonance images does predict short-term
      reduction in pain after transforaminal ESI (Class II and III studies). For
      patients with lumbar radicular pain, there is both insufficient and conflicting
      evidence that either supports or refutes prognostic accuracy of high-sensitivity
      C-reactive protein in determining epidural steroid outcomes (two Class III
      studies). It is probable that interferon gamma (IFN-gamma) more than 10 pg/mL
      from epidural lavage is predictive of short-term pain reduction after lumbar ESI
      (single Class I study). There is insufficient evidence that either supports or
      refutes prognostic accuracy of fibronectin-aggrecan complex from epidural lavage
      to determine epidural steroid outcome (single Class IV study). CONCLUSIONS:
      Predictive tools for ESI outcomes, such as nerve root compression grading and
      inflammatory markers, particularly, elevated IFN-gamma from epidural lavage
      fluid, seem promising in the future. At this time, future research is needed with
      a larger sample size, broader spectrum of patients, and a more defined system of
      outcome measurements at standardized follow-up periods before practice
      recommendations can be made.

PMID- 24743065
TI  - Review of research on the mechanical properties of the human tooth.
AB  - 'Bronze teeth' reflect the mechanical properties of natural teeth to a certain
      extent. Their mechanical properties resemble those of a tough metal, and the
      gradient of these properties lies in the direction from outside to inside. These
      attributes confer human teeth with effective mastication ability. Understanding
      the various mechanical properties of human teeth and dental materials is the
      basis for the development of restorative materials. In this study, the elastic
      properties, dynamic mechanical properties (visco-elasticity) and fracture
      mechanical properties of enamel and dentin were reviewed to provide a more
      thorough understanding of the mechanical properties of human teeth.

PMID- 24743068
TI  - Using the EC decision on case definitions for communicable diseases as a
      terminology source--lessons learned.
AB  - Extracting scientifically accurate terminology from an EU public health
      regulation is part of the knowledge engineering work at the European Centre for
      Disease Prevention and Control (ECDC). ECDC operates information systems at the
      crossroads of many areas - posing a challenge for transparency and consistency.
      Semantic interoperability is based on the Terminology Server (TS). TS value sets
      (structured vocabularies) describe shared domains as "diseases", "organisms",
      "public health terms", "geo-entities" "organizations" and "administrative terms"
      and others. We extracted information from the relevant EC Implementing Decision
      on case definitions for reporting communicable diseases, listing 53 notifiable
      infectious diseases, containing clinical, diagnostic, laboratory and
      epidemiological criteria. We performed a consistency check; a simplification -
      abstraction; we represented lab criteria in triplets: as 'y' procedural result
      /of 'x' organism-substance/on 'z' specimen and identified negations. The
      resulting new case definition value set represents the various formalized
      criteria, meanwhile the existing disease value set has been extended, new signs
      and symptoms were added. New organisms enriched the organism value set. Other new
      categories have been added to the public health value set, as transmission modes;
      substances; specimens and procedures. We identified problem areas, as (a) some
      classification error(s); (b) inconsistent granularity of conditions; (c)
      seemingly nonsense criteria, medical trivialities; (d) possible logical errors,
      (e) seemingly factual errors that might be phrasing errors. We think our
      hypothesis regarding room for possible improvements is valid: there are some open
      issues and a further improved legal text might lead to more precise epidemiologic
      data collection. It has to be noted that formal representation for automatic
      classification of cases was out of scope, such a task would require other
      formalism, as e.g. those used by rule-based decision support systems. 

PMID- 24743066
TI  - Changes in low-density lipoprotein cholesterol levels after discharge for acute
      myocardial infarction in a real-world patient population.
AB  - Aggressively managing low-density lipoprotein cholesterol (LDL-C) after
      myocardial infarction (MI) is a cornerstone of secondary prevention. The changes
      in LDL-C after MI and the factors associated with LDL-C levels are unknown.
      Therefore, we directly measured fasting LDL-C levels in 797 MI patients from 24
      US hospitals from 2005 to 2008. Mean LDL-C levels at discharge, 1 month, and 6
      months were 95.1, 81.9, and 87.1 mg/dL, respectively. In a hierarchical,
      multivariable, repeated measures model, older age, male sex, and hypertension
      were associated with lower LDL-C levels, whereas self-reported avoidance of
      health care because of cost was associated with higher LDL-C. Both the presence
      and intensity of statin therapy at discharge were strongly associated with LDL-C
      levels, with adjusted mean 6-month changes of -3.4 mg/dL (95% confidence interval
      (CI): -12.1, 5.3) for no statins; 1.7 mg/dL (95% CI: -4.7, 8.1) for low statins; 
      10.2 mg/dL (95% CI: -14.5, -6.0) for moderate statins; and -13.9 mg/dL (95% CI: 
      19.7, -8.0) for intensive statins (P < 0.001). In conclusion, we found that
      greater reductions in LDL-C levels after MI were strongly associated with the
      presence and intensity of statin therapy, older age, male sex, hypertension, and
      better socioeconomic status. These findings support the use of intensive statin
      therapy in post-MI patients and provide estimates of the expected LDL-C changes
      after MI in a real-world population. 

PMID- 24743069
TI  - Arranging ISO 13606 archetypes into a knowledge base using UML connectors.
AB  - To enable the efficient reuse of standard based medical data we propose to
      develop a higher-level information model that will complement the archetype model
      of ISO 13606. This model will make use of the relationships that are specified in
      UML to connect medical archetypes into a knowledge base within a repository. UML
      connectors were analysed for their ability to be applied in the implementation of
      a higher-level model that will establish relationships between archetypes. An
      information model was developed using XML Schema notation. The model allows
      linking different archetypes of one repository into a knowledge base. Presently
      it supports several relationships and will be advanced in future. 

PMID- 24743070
TI  - Ontologies to capture adverse events following immunisation (AEFI) from real
      world health data.
AB  - Immunisation is an important part of health care and adverse events following
      immunisation (AEFI) are relatively rare. AEFI can be detected through long term
      follow up of a cohort or from looking for signals from real world, routine data;
      from different health systems using a variety of clinical coding systems. Mapping
      these is a challenging aspect of integrating data across borders. Ontological
      representations of clinical concepts provide a method to map similar concepts, in
      this case AEFI across different coding systems. We describe a method using
      ontologies to be flag definite, probable or possible cases. We use Guillain-Barre
      syndrome (GBS) as an AEFI to illustrate this method, and the Brighton
      collaboration's case definition of GBS as the gold standard. Our method can be
      used to flag definite, probable or possible cases of GBS. Whilst there has been
      much research into the use of ontologies in immunisation these have focussed on
      database interrogation; where ours looks to identify varying signal strength. 

PMID- 24743071
TI  - Comparison of clinical practice guidelines from a knowledge modelling
      perspective: a case study with the management of hypertension.
AB  - Hypertension, as a cardiovascular risk factor, is a public health issue for which
      many clinical practice guidelines (CPGs) are published. In order to build the
      knowledge base of a clinical decision support system for the management of
      hypertension, we analysed three contemporary (2013) CPGs written in French on
      hypertension in a knowledge modelling perspective. We developed a semi-automated
      method using natural language processing called term extraction. Relevant
      candidate terms have been mapped to medical concepts to produce the conceptual
      coverage of each CPG. Only 53% of the 88 identified concepts were shared by the
      three guidelines. While sharing concepts does not warrantee that CPGs contents
      are similar, this also emphasizes guideline specificities. Such specificities
      could enrich the knowledge base of decision support systems by broadening their
      scope. 

PMID- 24743073
TI  - Practical implementation of a bridge between legacy EHR system and a clinical
      research environment.
AB  - Employing the bridge between Clinical Information System (CIS) and Clinical
      Research Environment (CRE) can provide functionality, which is not easily,
      implemented by traditional legacy EHR system. In this paper, the experience of
      such implementation at the University Hospitals of Geneva is described. General
      overview of the mapping of extracted from CIS data to the i2b2 Clinical Data
      Warehouse is provided. The defined implementation manages to provide the
      interoperability for the CRE. 

PMID- 24743074
TI  - Automated detection of ambiguity in BI-RADS assessment categories in mammography
      reports.
AB  - An unsolved challenge in biomedical natural language processing (NLP) is
      detecting ambiguities in the reports that can help physicians to improve report
      clarity. Our goal was to develop NLP methods to tackle the challenges of
      identifying ambiguous descriptions of the laterality of BI-RADS Final Assessment
      Categories in mammography radiology reports. We developed a text processing
      system that uses a BI-RADS ontology we built as a knowledge source for automatic
      annotation of the entities in mammography reports relevant to this problem. We
      used the GATE NLP toolkit and developed customized processing resources for
      report segmentation, named entity recognition, and detection of mismatches
      between BI-RADS Final Assessment Categories and mammogram laterality. Our system
      detected 55 mismatched cases in 190 reports and the accuracy rate was 81%. We
      conclude that such NLP techniques can detect ambiguities in mammography reports
      and may reduce discrepancy and variability in reporting. 

PMID- 24743075
TI  - Data and knowledge in medical distributed applications.
AB  - Building a clinical decision support system (CDSS) capable to collect process and
      diagnose data from the patients automatically, based on information, symptoms and
      investigations is one of the current challenges for researchers and medical
      science. The purpose of the current study is to design a cloud-based CDSS to
      improve patient safety, quality of care and organizational efficiency. It
      presents the design of a cloud-based application system using a medical based
      approach, which covers different diseases to diagnosis, differentiated on most
      important pathologies. Using online questionnaires, traditional and new data will
      be collected from patients. After data input, the application will formulate a
      presumptive diagnosis and will direct patients to the correspondent department. A
      questionnaire will dynamically ask questions about the interface, and
      functionality improvements. Based on the answers, the functionality of the system
      and the user interface will be improved considering the real needs expressed by
      the end-users. The cloud-based CDSS, as a useful tool for patients, physicians
      and healthcare providers involves the computer support in the diagnosis of
      different pathologies and an accurate automatic differential diagnostic system. 

PMID- 24743076
TI  - Computer assisted treatment prediction of low back pain pathologies.
AB  - The paper presents a fuzzy inference system based prediction with the role to
      determine the appropriate action for patients that presents lower back pain. If
      not treated correctly lower back pain can degenerate in various diseases. The
      system infers three possible actions: (1) spinal cord surgery, (2) medication
      combined with exercises and (3) no action needed. The system takes in
      consideration the age and sex of the patient, a pain intensity parameter, the
      metabolic rate of the patient and mobility parameters from the Zebris Mobility
      device. In total 243 rules have been formulated but only 21% of the rules
      suggests surgery. The initial results are promising; there is a correlation of
      0.83% between the control results and the results from the system. 

PMID- 24743077
TI  - Preclinical tests of an android based dietary logging application.
AB  - The paper describes the first, preclinical evaluation of a dietary logging
      application developed at the University of Pannonia, Hungary. The mobile user
      interface is briefly introduced. The three evaluation phases examined the
      completeness and contents of the dietary database and the time expenditure of the
      mobile based diet logging procedure. The results show that although there are
      substantial individual differences between various dietary databases, the
      expectable difference with respect to nutrient contents is below 10% on typical
      institutional menu list. Another important finding is that the time needed to
      record the meals can be reduced to about 3 minutes daily especially if the user
      uses set-based search. CONCLUSION: a well designed user interface on a mobile
      device is a viable and reliable way for a personalized lifestyle support service.

PMID- 24743078
TI  - The Israel National Hospital Discharge Register: an essential component of data
      driven healthcare.
AB  - The Israel National Hospital Discharge Register (INHDR) is an essential section
      of healthcare data. It includes record for each admission to hospital wards
      during the last twenty years, and the data are increasing by digitally updated
      information from hospitals on continually a monthly or quarterly basis. The
      register contains encrypted patient identity number, admission number,
      demographic and geographic data, hospitalization data, diagnoses, procedures and
      accounting data. The goal of the register is to measure medical and surgical
      services in hospitals, to compare hospital activity among regions, gender and age
      and population groups within the country and among other countries, to analyse
      the difference between periods. This large-scale hospital data helps in planning
      of the hospital services, analysing the health status of the population, disease
      and injury surveillance, and helps in performance of quality indicators. It
      assists decision makers at the Ministry of Health (MOH) in their daily and on
      going missions. 

PMID- 24743079
TI  - Supporting diagnosis and treatment in medical care based on Big Data processing.
AB  - With information and data in all domains growing every day, it is difficult to
      manage and extract useful knowledge for specific situations. This paper presents
      an integrated system architecture to support the activity in the Ob-Gin
      departments with further developments in using new technology to manage Big Data
      processing - using Google BigQuery - in the medical domain. The data collected
      and processed with Google BigQuery results from different sources: two Obstetrics
      & Gynaecology Departments, the TreatSuggest application - an application for
      suggesting treatments, and a home foetal surveillance system. Data is uploaded in
      Google BigQuery from Bega Hospital Timisoara, Romania. The analysed data is
      useful for the medical staff, researchers and statisticians from public health
      domain. The current work describes the technological architecture and its
      processing possibilities that in the future will be proved based on quality
      criteria to lead to a better decision process in diagnosis and public health. 

PMID- 24743080
TI  - From generic pathways to ICT-supported horizontally integrated care: the
      SmartCare approach and convergence with future Internet assembly.
AB  - Successful service integration in policy and practice requires both technology
      innovation and service process innovation being pursued and implemented at the
      same time. The SmartCare project (partially EC-funded under CIP ICT PSP Program)
      aims to achieve this through development, piloting and evaluation of ICT-based
      services, horizontally integrating health and social care in ten pilot regions,
      including Kraljevo region in Serbia. The project has identified and adopted two
      generic highest-level common thematic pathways in joint consolidation phase -
      integrated support for long-term care and integrated support after hospital
      discharge. A common set of standard functional specifications for an open ICT
      platform enabling the delivery of integrated care is being defined, around the
      challenges of data sharing, coordination and communication in these two
      formalized pathways. Implementation and system integration on technology and
      architecture level are to be based on open standards, multivendor
      interoperability, and leveraging on the current evolving open specification
      technology foundations developed in relevant projects across the European
      Research Area. 

PMID- 24743081
TI  - Combined model for diabetes lifestyle support.
AB  - Treatment of diabetes mellitus is a public health related problem of modern
      healthcare. Surveys show that current methods to estimate the required amount of
      insulin are quite inefficient in practice as they are based on experience. This
      paper offers a new approach to predict the glucose level of people with diabetes.
      It combines two efficient models of the literature: one for nutrient absorption
      and one for glucose control. The combination of them tracks the blood sugar level
      considering nutrition composition, applied insulin and initial glucose level.
      Compared to already existing mixed meal models, the current version takes into
      account a more detailed nutrition composition (protein, lipid, monosaccharide,
      fiber and starch) supported by our expert dietary systems. Although the model
      gives satisfactory results even with parameter sets taken from literature,
      parameter training by genetic algorithms yields a better tracking of the
      patients. 

PMID- 24743083
TI  - Belgian primary care EPR: assessment of nationwide routine data extraction.
AB  - Starting in 2009, the first ever Belgian nationwide data collection network using
      routine data extracted from primary care EPR (upload method) has been built from
      scratch. The network also uses a manual web-based data collection method. This
      paper compares these two methods by analysing missing and most recent values for
      certain parameters. We collected data from 4954 practices, pertaining to 29,180
      patients. Mean values for the most recent parameters were similar regardless of
      which data collection method was used. Many missing recent values (>46%) were
      found for all of the parameters when using the upload method. It seems that, in
      Belgium, uploading routine data from primary care EPR on a large scale is
      suitable and allows the collection of chronological retrospective data. However,
      the method still requires major, carefully controlled improvements. 

PMID- 24743084
TI  - Improving hospital decision making with interpretable associations over
      datacubes.
AB  - In this paper we propose a new Classification based on Association Rules (CAR)
      algorithm that improves the interpretability of the results, works over real data
      from the electronic health records (EHRs), and allows the study of the patient as
      a whole. It enables tasks such as the discovery of relationships between
      diseases, or offering several alternative and reasoned diagnoses for the cases of
      patients with several diseases that analysed separately could lead to mistaken
      diagnosis. We aim to achieve several goals: to discover hidden relationships; to
      improve the interpretability and reduce the complexity of the result; to obtain
      more reliable diagnosis (getting alternative reasoned diagnoses and higher
      robustness to noisy rules), and to improve the quality of the classifier avoiding
      the usual over-fitting problem. To this purpose, we define and exploit
      hierarchies defined over datacubes dimensions, and change the way the association
      rules are obtained, and their evaluation at the classification process. To prove
      the utility of our proposal we have used it in an example of cancer
      discrimination. 

PMID- 24743085
TI  - The effect of the waiting times on the patient pathways for patients with
      suspected coronary artery disease.
AB  - The paper describes the investigation of the Hungarian public administrative
      health databases with the aim to identify hidden correspondences in the patients'
      evaluation pathways for patients with suspected coronary artery disease (CAD). In
      our current work we investigated the effect of the waiting times of invasive and
      non-invasive investigations in the evaluation pathways of patients with suspected
      CAD. We found a considerable correlation between waiting times and the further
      course of the patients. 

PMID- 24743086
TI  - Routine data for disease surveillance in the undeveloped region of the OR Tambo
      district of the Eastern Cape Province.
AB  - The research team needed to upsize the solution previously tested so that it
      could expand the routine data collected via tablet computers. The research team
      identified the general flow of data within clinics. Data was mainly collected
      from registers, which were later converted to electronic form and checked for
      duplication. A database was designed for the collection of demographic data
      (Patient Master Index), which was aimed at eliminating duplication of patients'
      data in several registers. Open Data Kit (ODK) Collect was setup on Android
      tablets for collecting disease related routine data, while ODK Aggregate as the
      storage and aggregates of data captured by ODK Collect and the Patient Master
      Index for demographic data, were setup on an Apple Mini Mac server. Data
      collection is in progress. The expected results include improved data quality,
      reliability and quick access to summary data. Secondly, instant retrieval of
      patient demographic details and clinic numbers are included. Thirdly, ability to
      form standard reporting from the SQL database and lastly exporting data into the
      TIER.net and DHIS systems via CVS files thus eliminating the need for data
      capturers are shown. 

PMID- 24743087
TI  - Usability of HL7 and SNOMED CT standards in Java Persistence API environment.
AB  - Due to the need for an efficient way of communication between the different
      stakeholders of healthcare (e.g. doctors, pharmacists, hospitals, patients etc.),
      the possibility of integrating different healthcare systems occurs. However,
      during the integration process several problems of heterogeneity might come up,
      which can turn integration into a difficult task. These problems motivated the
      development of healthcare information standards. The main goal of the HL7 family
      of standards is the standardization of communication between clinical systems and
      the unification of clinical document formats on the structural level. The SNOMED
      CT standard aims the unification of the healthcare terminology, thus the
      development of a standard on lexical level. The goal of this article is to
      introduce the usability of these two standards in Java Persistence API (JPA)
      environment, and to examine how standard-based system components can be
      efficiently generated. First, we shortly introduce the structure of the
      standards, their advantages and disadvantages. Then, we present an architecture
      design method, which can help to eliminate the possible structural drawbacks of
      the standards, and makes code generating tools applicable for the automatic
      production of certain system components.

PMID- 24743088
TI  - New study program: Interdisciplinary Postgraduate Specialist Study in Medical
      Informatics.
AB  - Paper presents an overview of the EU funded Project of Curriculum Development for
      Interdisciplinary Postgraduate Specialist Study in Medical Informatics named
      MEDINFO to be introduced in Croatia. The target group for the program is formed
      by professionals in any of the areas of medicine, IT professionals working on
      applications of IT for health and researchers and teachers in medical
      informatics. In addition to Croatian students, the program will also provide
      opportunity for enrolling students from a wider region of Southeast Europe.
      Project partners are two faculties of the University of Zagreb - Faculty of
      Organization and Informatics from Varazdin and School of Medicine, Andrija
      Stampar School of Public Health from Zagreb with the Croatian Society for Medical
      Informatics, Croatian Chamber of Economy, and Ericsson Nikola Tesla Company as
      associates. 

PMID- 24743090
TI  - Evaluating study for a multiuser oriented medical data visualization method.

PMID- 24743091
TI  - Mobile learning readiness of nursing students.

PMID- 24743092
TI  - Application of electronic health record system for teaching medical students.

PMID- 24743093
TI  - Proof of concept using tablet computers to survey TB.

PMID- 24743096
TI  - Studies in Health Technology and Informatics. Preface.

PMID- 24743099
TI  - Isolating disparity or synthesizing equity? Transdisciplinarity and
      intersectionality in adult and geriatric oncology.

PMID- 24743097
TI  - A general approach for haplotype phasing across the full spectrum of relatedness.
AB  - Many existing cohorts contain a range of relatedness between genotyped
      individuals, either by design or by chance. Haplotype estimation in such cohorts
      is a central step in many downstream analyses. Using genotypes from six cohorts
      from isolated populations and two cohorts from non-isolated populations, we have
      investigated the performance of different phasing methods designed for nominally
      'unrelated' individuals. We find that SHAPEIT2 produces much lower switch error
      rates in all cohorts compared to other methods, including those designed
      specifically for isolated populations. In particular, when large amounts of IBD
      sharing is present, SHAPEIT2 infers close to perfect haplotypes. Based on these
      results we have developed a general strategy for phasing cohorts with any level
      of implicit or explicit relatedness between individuals. First SHAPEIT2 is run
      ignoring all explicit family information. We then apply a novel HMM method
      (duoHMM) to combine the SHAPEIT2 haplotypes with any family information to infer
      the inheritance pattern of each meiosis at all sites across each chromosome. This
      allows the correction of switch errors, detection of recombination events and
      genotyping errors. We show that the method detects numbers of recombination
      events that align very well with expectations based on genetic maps, and that it
      infers far fewer spurious recombination events than Merlin. The method can also
      detect genotyping errors and infer recombination events in otherwise
      uninformative families, such as trios and duos. The detected recombination events
      can be used in association scans for recombination phenotypes. The method
      provides a simple and unified approach to haplotype estimation, that will be of
      interest to researchers in the fields of human, animal and plant genetics. 

PMID- 24743100
TI  - How do physicians adopt and apply opioid prescription guidelines in the emergency
      department? A qualitative study.
AB  - STUDY OBJECTIVE: An increase in prescriptions for opioid pain medications has
      coincided with increasing opioid overdose deaths. Guidelines designed to optimize
      opioid prescriptions written in the emergency department have been implemented,
      with substantial controversy. Little is known about how physicians perceive and
      apply these guidelines. We seek to identify key themes about emergency
      physicians' definition, awareness, use, and opinions of opioid-prescribing
      guidelines. METHODS: We conducted semistructured qualitative interviews with a
      convenience sample of 61 emergency physicians attending the American College of
      Emergency Physicians Scientific Assembly (October 2012, Denver, CO). Participants
      varied with respect to age, sex, geographic region, practice setting, and years
      of practice experience. We analyzed the interview content with modified grounded
      theory, an iterative coding process to identify patterns of responses and derive
      key themes. The study team examined discrepancies in the coding process to ensure
      reliability and establish consensus. RESULTS: When aware of opioid-prescribing
      guidelines, emergency physicians often defined them as policies developed by
      individual hospitals that sometimes reflected guidelines at the state or national
      level. Guidelines were primarily used by physicians to communicate decisions to
      limit prescriptions to patients on discharge rather than as tools for
      decisionmaking. Attitudes toward guidelines varied with regard to general
      attitudes toward opioid medications, as well as the perceived effects of
      guidelines on physician autonomy, public health, liability, and patient
      diversion. CONCLUSION: These exploratory findings suggest that hospital-based
      opioid guidelines complement and occasionally supersede state and national
      guidelines and that emergency physicians apply guidelines primarily as
      communication tools. The perspectives of providers should inform future policy
      actions that seek to address the problem of opioid abuse and overdose through
      practice guidelines.

PMID- 24743101
TI  - Physician orders for life-sustaining treatment and emergency medicine: ethical
      considerations, legal issues, and emerging trends.
AB  - Since its original development in Oregon in 1993, Physician Orders for Life
      Sustaining Treatment (POLST) is quickly growing in popularity and prevalence as a
      method of communicating the end-of-life care preferences for the seriously ill
      and frail nationwide. Early evidence has suggested significant advantages over
      advance directives and do-not-resuscitate/do-not-intubate documents both in
      accuracy and penetration within relevant populations. POLST also may contribute
      to the quality of end-of-life care administered. Although it was designed to be
      as clear as possible, unexpected challenges in the interpretation and use of
      POLST in the emergency department do exist. In this article, we will discuss the
      history, ethical considerations, legal issues, and emerging trends in the use of
      POLST documents as they apply to emergency medicine.

PMID- 24743102
TI  - Does the multiple mini-interview address stakeholder needs? An applicant's
      perspective.

PMID- 24743103
TI  - In vivo monitoring of the antiangiogenic effect of neurotensin receptor-mediated
      radiotherapy by small-animal positron emission tomography: a pilot study.
AB  - The neurotensin receptor (NTS1) has emerged as an interesting target for
      molecular imaging and radiotherapy of NTS-positive tumors due to the
      overexpression in a range of tumors. The aim of this study was to develop a 177Lu
      labeled NTS1 radioligand, its application for radiotherapy in a preclinical model
      and the imaging of therapy success by small-animal positron emission tomography
      (uPET) using [68Ga]DOTA-RGD as a specific tracer for imaging angiogenesis. The
      177Lu-labeled peptide was subjected to studies on HT29-tumor-bearing nude mice in
      vivo, defining four groups of animals (single dose, two fractionated doses, four
      fractionated doses and sham-treated animals). Body weight and tumor diameters
      were determined three times per week. Up to day 28 after treatment, uPET studies
      were performed with [68Ga]DOTA-RGD. At days 7-10 after treatment with four
      fractionated doses of 11-14 MBq (each at days 0, 3, 6 and 10), the tumor growth
      was slightly decreased in comparison with untreated animals. Using a single high
      dose of 51 MBq, a significantly decreased tumor diameter of about 50% was
      observed with the beginning of treatment. Our preliminary PET imaging data
      suggested decreased tumor uptake values of [68Ga]DOTA-RGD in treated animals
      compared to controls at day 7 after treatment. This pilot study suggests that
      early PET imaging with [68Ga]DOTA-RGD in radiotherapy studies to monitor integrin
      expression could be a promising tool to predict therapy success in vivo. Further
      successive PET experiments are needed to confirm the significance and predictive
      value of RGD-PET for NTS-mediated radiotherapy. 

PMID- 24743104
TI  - Tolerance to seizure induced by kainic acid is produced in a specific period of
      zebrafish development.
AB  - During brain development, the electrical disturbance promoted by a seizure can
      have several consequences, because it can disturb a set of steps extremely
      regulated needed to the correct brain maturation. Animal modeling of seizure is
      invaluable to contribute to the mechanistic understanding of punctual seizure
      event, and those that triggered in an immature neural network could alter the
      mature brain physiology. In the present study we observed that the exposure to
      kainic acid diluted directly in water of zebrafish decreased the locomotor
      activity at 7 days post-fertilization (dpf) animals and increased at 15 dpf,
      despite the absence of more specific seizure features. Pre-exposure to kainic
      acid (500 MUM) diluted in water at 7 dpf animals reduced the susceptibility to a
      second exposure 2 months later by intraperitoneal injection. The current data
      suggest that these different responses are associated with neuronal maturation
      process and open a question about the window of development that are crucial to
      long lasting effects related to seizure in this animal model.

PMID- 24743105
TI  - Advances in exercise, fitness, and performance genomics in 2013.
AB  - The most significant and scientifically sound articles in exercise genomics that
      were published in 2013 are reviewed in this report. No article on the genetic
      basis of sedentary behavior or physical activity level was identified. A
      calcineurin- and alpha actinin-2-based mechanism has been identified as the
      potential molecular basis for the observed lower muscular strength and power in
      alpha actinin-3-deficient individuals. Although baseline muscle transcriptomic
      signatures were found to be associated with strength training-induced muscle
      hypertrophy, no predictive genomic variants could be identified as of yet. One
      study found no clear evidence that the inverse relation between physical activity
      level and incident CHD events was influenced by 58 genomic variants clustered
      into four genetic scores. Lower physical activity level in North American
      populations may be driving the apparent risk of obesity in fat mass- and obesity
      associated gene (FTO)-susceptible individuals compared with more active
      populations. Two large studies revealed that common genetic variants associated
      with baseline levels of plasma HDL cholesterol and triglycerides are not clear
      predictors of changes induced by interventions focused on weight loss, diet, and
      physical activity behavior. One large study from Japan reported that a higher
      fitness level attenuated the arterial stiffness-promoting effect of the Ala54
      allele at the fatty acid binding protein 2 locus, which is a controversial
      finding because previous studies have suggested that Thr54 was the risk allele.
      Using transcriptomics to generate genomic targets in an unbiased manner for
      subsequent DNA sequence variants studies appears to be a growing trend. Moreover,
      exercise genomics is rapidly embracing gene and pathway analysis to better define
      the underlying biology and provide a foundation for the study of human variation.

PMID- 24743106
TI  - Muscle function, dynamic loading, and femoral neck structure in pediatric
      females.
AB  - PURPOSE: Muscle forces influence the development of bone mass and structure, but
      dynamic loading via impact exercise is considered particularly osteogenic. We
      hypothesized that indices of local muscle function and physical activity exposure
      would predict femoral neck (FN) structure in premenarcheal females. METHODS: We
      tested this hypothesis in 76 healthy, premenarcheal girls (46 gymnasts and 30
      nongymnasts). Height, weight, Tanner breast stage, and prior year nonaquatic,
      organized physical activity level (PAL) were recorded semiannually. Hologic dual
      energy x-ray absorptiometry scans (whole body, left FN) yielded total body
      nonbone lean mass and bone outcomes, including narrow neck (NN) hip structural
      analysis data. Dynamometers assessed nondominant hand grip and left hip
      flexion/extension indices. Parsimonious regression models tested the following as
      predictors of bone outcomes: local muscle function, PAL, gymnast status, and lean
      mass, accounting for Tanner breast stage and height, as appropriate. RESULTS: Hip
      flexion indices were significantly correlated with indices of FN mass, density,
      structure, and strength (P < 0.05). However, the entry of PAL, gymnast status,
      and lean mass into regression models supplanted local muscle function explanatory
      value. In contrast, for many variables, the significant association of gymnast
      status persisted after accounting for physical maturity, body size/lean mass, and
      PAL. For all skeletal indices except FNArea, NNwidth, NN endosteal diameter, and
      NN buckling ratio, gymnast status was more strongly associated with bone outcomes
      than PAL. CONCLUSIONS: Greater activity doses and exposure to extreme dynamic
      loading provide independent benefits to FN structure during growth. Furthermore,
      weight-bearing activity and high-impact exercise exposure appear superior to
      local muscle force measures for prediction of FN structure.

PMID- 24743107
TI  - Incidental and Planned Exercise Questionnaire for seniors: validity and
      responsiveness.
AB  - PURPOSE: This study assessed the criterion validity and responsiveness of the
      Incidental and Planned Exercise Questionnaire (IPEQ) specifically developed for
      aging research. METHODS: The sample comprised 315 community-dwelling inactive
      older adults (mean age = 73.2 yr) who participated in a trial investigating the
      effect of a walking program on falls. At baseline, a subsample (n = 177) also
      wore an accelerometer (ActiGraph GT1M) for 7 d, and 126 of those had four valid
      days or more of accelerometer data. Validity coefficients (Spearman rho) were
      calculated between accelerometer counts per minute, average steps per day,
      average moderate- to vigorous-intensity physical activity (MVPA) using two cut
      points (760 and 1041 counts per minute), and IPEQ-MVPA (the sum of physical
      activity hours per week derived from nine IPEQ items excluding the indoor chores
      question). Responsiveness was the mean IPEQ change in the intervention group
      divided by the SD of the mean change in control group. RESULTS: The correlation
      coefficients between IPEQ-MVPA and counts per minute per day and steps per day
      were 0.33 and 0.31, respectively. The coefficients with accelerometer MVPA at low
      and medium cut points were 0.29 and 0.33, respectively, and 0.26 and 0.35 for
      walking. The Bland-Altman plot showed increased errors with higher values of IPEQ
      MVPA. IPEQ incidental physical activity questions and IPEQ as a whole were
      significantly correlated with accelerometer light intensity (100-760 counts per
      minute, rho = 0.29 and 0.23). The 12-month responsiveness of total IPEQ was 0.30
      and 0.44 for the "planned walking" item. CONCLUSIONS: IPEQ provides a practical
      and valid measure of MVPA in surveillance and intervention studies. Incidental
      activities are mostly of a light-intensity nature, and their low ambulatory
      component may explain the lower correlation between IPEQ as a whole and
      accelerometer measures.

PMID- 24743108
TI  - Increased resistance during jump exercise does not enhance cortical bone
      formation.
AB  - PURPOSE: This study sought to elucidate the effects of a low- and high-load jump
      resistance exercise (RE) training protocol on cortical bone of the tibia and
      femur mid-diaphyses. METHODS: Sprague-Dawley rats (male, 6 months old) were
      randomly assigned to high-load RE (HRE; n = 16), low-load RE (LRE; n = 15), or
      cage control (CC; n = 11) groups. Animals in the HRE and LRE groups performed 15
      sessions of jump RE for 5 wk. Load in the HRE group was progressively increased
      from 80 g added to a weighted vest (50 repetitions) to 410 g (16 repetitions).
      The LRE rats completed the same protocol as the HRE group (same number of
      repetitions), with only a 30-g vest applied. RESULTS: Low- and high-load jump RE
      resulted in 6%-11% higher cortical bone mineral content and cortical bone area
      compared with controls, as determined by in vivo peripheral quantitative computed
      tomography measurements. In the femur, however, only LRE demonstrated
      improvements in cortical volumetric bone mineral density (+11%) and cross
      sectional moment of inertia (+20%) versus the CC group. The three-point bending
      to failure revealed a marked increase in tibial maximum force (25%-29%),
      stiffness (19%-22%), and energy to maximum force (35%-55%) and a reduction in
      elastic modulus (-11% to 14%) in both LRE and HRE compared with controls. Dynamic
      histomorphometry assessed at the tibia mid-diaphysis determined that both LRE and
      HRE resulted in 20%-30% higher periosteal mineralizing surface versus the CC
      group. Mineral apposition rate and bone formation rate were significantly greater
      in animals in the LRE group (27%, 39%) than those in the HRE group. CONCLUSION:
      These data demonstrate that jump training with minimal loading is equally, and
      sometimes more, effective at augmenting cortical bone integrity compared with
      overload training in skeletally mature rats.

PMID- 24743109
TI  - Aerobic capacity and cognitive control in elementary school-age children.
AB  - PURPOSE: The current study examined the relationship between children's
      performance on the Progressive Aerobic Cardiovascular Endurance Run subtest of
      the FitnessGram(r) and aspects of cognitive control that are believed to support
      academic success. METHODS: Hierarchical linear regression analyses were conducted
      on a sample of second- and third-grade children (n = 397) who completed modified
      versions of a flanker task and spatial n-back task to assess inhibitory control
      and working memory, respectively. RESULTS: Greater aerobic fitness was
      significantly related to shorter reaction time and superior accuracy during the
      flanker task, suggesting better inhibitory control and the facilitation of
      attention in higher-fit children. A similar result was observed for the n-back
      task such that higher-fit children exhibited more accurate target detection and
      discrimination performance when working memory demands were increased.
      CONCLUSIONS: These findings support the positive association between aerobic
      fitness and multiple aspects of cognitive control in a large sample of children,
      using a widely implemented and reliable field estimate of aerobic capacity.
      Importantly, the current results suggest that this relationship is consistent
      across methods used to assess fitness, which may have important implications for
      extending this research to more representative samples of children in a variety
      of experimental contexts.

PMID- 24743110
TI  - Earbud-based sensor for the assessment of energy expenditure, HR, and VO2max.
AB  - INTRODUCTION/PURPOSE: The goal of this program was to determine the feasibility
      of a novel noninvasive, highly miniaturized optomechanical earbud sensor for
      accurately estimating total energy expenditure (TEE) and maximum oxygen
      consumption (VO2max). The optomechanical sensor module, small enough to fit
      inside commercial audio earbuds, was previously developed to provide a seamless
      way to measure blood flow information during daily life activities. The sensor
      module was configured to continuously measure physiological information via
      photoplethysmography and physical activity information via accelerometry. This
      information was digitized and sent to a microprocessor where digital signal
      processing algorithms extract physiological metrics in real time. These metrics
      were streamed wirelessly from the earbud to a computer. METHODS: In this study,
      23 subjects of multiple physical habitus were divided into a training group of 14
      subjects and a validation group of 9 subjects. Each subject underwent the same
      exercise measurement protocol consisting of treadmill-based cardiopulmonary
      exercise testing to reach VO2max. Benchmark sensors included a 12-lead ECG sensor
      for measuring HR, a calibrated treadmill for measuring distance and speed, and a
      gas-exchange analysis instrument for measuring TEE and VO2max. The earbud sensor
      was the device under test. Benchmark and device under test data collected from
      the 14-person training data set study were integrated into a preconceived
      statistical model for correlating benchmark data with earbud sensor data.
      Coefficients were optimized, and the optimized model was validated in the 9
      person validation data set. RESULTS: It was observed that the earbud sensor
      estimated TEE and VO2max with mean +/- SD percent estimation errors of -0.7 +/-
      7.4% and -3.2 +/- 7.3%, respectively. CONCLUSION: The earbud sensor can
      accurately estimate TEE and VO2max during cardiopulmonary exercise testing.

PMID- 24743111
TI  - Transvaginal methotrexate injection for the treatment of cesarean scar pregnancy:
      efficacy and subsequent fecundity.
AB  - STUDY OBJECTIVE: To investigate the efficacy of local methotrexate (MTX)
      injections under transvaginal ultrasound guidance for treatment of cesarean scar
      pregnancy (CSP) and to assess fecundity after treatment. DESIGN: Retrospective
      review (Canadian Task Force classification II-3). SETTING: University hospital.
      PATIENTS: Eight women with CSP. INTERVENTION: Transvaginal MTX injection.
      MEASUREMENTS AND MAIN RESULTS: We retrospectively reviewed 8 CSP cases treated
      with local MTX injection under transvaginal ultrasonographic guidance. In all
      cases, the serum human chorionic gonadotropin concentration was monitored and the
      gestational sac was evaluated using ultrasonography after treatment. Magnetic
      resonance imaging was performed as necessary. Patient clinical characteristics,
      clinical course after treatment, treatment efficacy, and fecundity after
      treatment in patients desiring subsequent pregnancies were evaluated. All 8 women
      were successfully treated without the need for blood transfusions or surgical
      procedures, although 2 required additional MTX therapy via local injection or
      systemic administration. The mean (SD) time to human chorionic gonadotropin
      normalization was 78.5 (37.7) days (range, 42-166 days). Four of 5 patients
      desiring subsequent pregnancies after the treatment had uneventful parturition,
      and recurrent CSP was diagnosed in 1 patient. CONCLUSIONS: Transvaginal MTX
      injection was effective and safe as sole treatment of CSP. Although the treatment
      course tended to be long, this method can be considered the first choice of
      treatment in patients desiring future pregnancies. However, careful attention
      should be paid to the possibility of CSP recurrence.

PMID- 24743112
TI  - Opportunity cost for early treatment of Chagas disease in Mexico.
AB  - BACKGROUND: Given current neglect for Chagas disease in public health programs in
      Mexico, future healthcare and economic development policies will need a more
      robust model to analyze costs and impacts of timely clinical attention of
      infected populations. METHODOLOGY/PRINCIPAL FINDINGS: A Markov decision model was
      constructed to simulate the natural history of a Chagas disease cohort in Mexico
      and to project the associated short and long-term clinical outcomes and
      corresponding costs. The lifetime cost for a timely diagnosed and treated Chagas
      disease patient is US$ 10,160, while the cost for an undiagnosed individual is
      US$ 11,877. The cost of a diagnosed and treated case increases 24-fold from early
      acute to indeterminate stage. The major cost component for lifetime cost was
      working days lost, between 44% and 75%, depending on the program scenario for
      timely diagnosis and treatment. CONCLUSIONS/SIGNIFICANCE: In the long term, it is
      cheaper to diagnose and treat chagasic patients early, instead of doing nothing.
      This finding by itself argues for the need to shift current policy, in order to
      prioritize and attend this neglected disease for the benefit of social and
      economic development, which implies including treatment drugs in the national
      formularies. Present results are even more relevant, if one considers that timely
      diagnosis and treatment can arrest clinical progression and enhance a chronic
      patient's quality of life.

PMID- 24743115
TI  - [Development and substantiation of complex approach to determination of
      individual intolerance and hypersensitivity to dental materials].
AB  - The aim of research was to define the most simple, objective and affordable test
      for determination of individual compatibility for dental materials before
      placement of prostheses in the oral cavity. After series of provocative and
      laboratory tests it was found that the most convenient is the muco-gingival test.
      Also found that absolutely all materials, including ceramics, can cause
      individual intolerance with more or less severe clinical symptoms. 

PMID- 24743113
TI  - Impact of inclusion of industry trial results registries as an information source
      for systematic reviews.
AB  - BACKGROUND: Clinical trial results registries may contain relevant unpublished
      information. Our main aim was to investigate the potential impact of the
      inclusion of reports from industry results registries on systematic reviews
      (SRs). METHODS: We identified a sample of 150 eligible SRs in PubMed via backward
      selection. Eligible SRs investigated randomized controlled trials of drugs and
      included at least 2 bibliographic databases (original search date: 11/2009). We
      checked whether results registries of manufacturers and/or industry associations
      had also been searched. If not, we searched these registries for additional
      trials not considered in the SRs, as well as for additional data on trials
      already considered. We reanalysed the primary outcome and harm outcomes reported
      in the SRs and determined whether results had changed. A "change" was defined as
      either a new relevant result or a change in the statistical significance of an
      existing result. We performed a search update in 8/2013 and identified a sample
      of 20 eligible SRs to determine whether mandatory results registration from
      9/2008 onwards in the public trial and results registry ClinicalTrials.gov had
      led to its inclusion as a standard information source in SRs, and whether the
      inclusion rate of industry results registries had changed. RESULTS: 133 of the
      150 SRs (89%) in the original analysis did not search industry results
      registries. For 23 (17%) of these SRs we found 25 additional trials and
      additional data on 31 trials already included in the SRs. This additional
      information was found for more than twice as many SRs of drugs approved from 2000
      as approved beforehand. The inclusion of the additional trials and data yielded
      changes in existing results or the addition of new results for 6 of the 23 SRs.
      Of the 20 SRs retrieved in the search update, 8 considered ClinicalTrials.gov or
      a meta-registry linking to ClinicalTrials.gov, and 1 considered an industry
      results registry. CONCLUSION: The inclusion of industry and public results
      registries as an information source in SRs is still insufficient and may result
      in publication and outcome reporting bias. In addition to an essential search in
      ClinicalTrials.gov, authors of SRs should consider searching industry results
      registries.

PMID- 24743116
TI  - Effect of benign testicular mass on fertility: an epidermoid cyst case.
AB  - The article discusses the problem of epidermoid cysts - extremely rare but the
      most common benign intratesticular tumors. The majority of non-palpable
      testicular lesions, discovered by ultrasonography in a population of infertile
      men, are benign tumors. The case of a young man who had incidentally diagnosed,
      during his infertility evaluation, a right testicular mass which was
      pathologically reported as epidermoid cyst after partial orchiectomy is
      presented. It was suggested that benign testicular cysts may effect the normal
      parenchyma of testis even if the normal histopathology. Thus, the excision of
      these benign lesions especially in infertile population is recommended. 

PMID- 24743117
TI  - A rare entity of benign bladder neoplasm: female lipoma.
AB  - Although benign bladder neoplasms constitute less than 5% of all bladder
      neoplasms, they should be taken into consideration because they can be
      symptomatic, and have the risk of confusing with other malignant neoplasms.
      Herein, we reported a 59-year-old female patient consulted to our outpatient
      clinic with the incidents of hematuria. During cystoscopic examination, a yellow
      coloured mass lesion with smooth contours on the right posterolateral wall of the
      bladder was observed. Histopathological examination of the specimen demonstrated
      mature adipose tissue contained within submucosal layer without bladder wall
      invasion. Bladder lipomas are rarely seen pure benign masses which almost all
      reported ones were men. We think that female cases should also be taken into
      consideration for differential diagnosis presenting with hematuria. 

PMID- 24743118
TI  - Application of sonography for evaluation of posterior circulation disorders.
AB  - Posterior circulation disorders (PCD) include a) vertebrobasilar insufficiency
      (VBI), which has a wide clinical manifestation such as vestibulocerebellar
      syndrome, cephalalgia, cochlear syndrome, vegetovascular dystonia, visual
      disturbances, "syndrome of vertebral artery compression" etc, b) vertebrobasilar
      TIA and c) stroke. All of them are caused by blood flow disturbances in vertebral
      (VA), basilar (BAS) and posterior cerebral arteries (PCA). Aim - evaluation of
      role of extracranial duplex-sonography (EDS), transcranial color-coded duplex
      sonography (TCCD) and rotational functional tests (RFT) in PCD. 88 patients (age
      range 18-62y) with PCD and 20 healthy controls with relevant age range were
      examined using EDS, TCCD and RFT with measurement of vertebral arteries (VA)
      diameter, mean flow velocities (MFV) and pulsatility index (PI) in VA, basilar
      artery (BAS) and posterior cerebral arteries (PCA). For statistical analysis SPSS
      software (Version 11.5) was used. In 48 (54,5%) patients revealed unilateral
      narrowing (less than 2.5 mm in diameter) and deformation of vertebral artery
      associated with osteochondrosis or primary hypoplasia. In 11 (12,5%) patients
      revealed bilateral narrowing (less than 2.8 mm in diameter) and deformation of
      vertebral arteries. Ultrasound investigation showed a decrease of MFV (23 +/- 1.4
      cm/sec) in the intracranial length of vertebral artery and an increase of PI (3,2
      +/-0,3 p=0,002) in the extracranial segments (V1- V3). In 52 cases (59%) revealed
      decrease of MFV in BAS by 32.6 +/- 4.7% and in 41 cases (46.5%) decrease of MFV
      in both PCA by 24.8 +/- 5.2% (P<0.002). In 21 cases (23.8%) revealed concurrent
      development of vertebrogenic reflex vasoconstriction. In 18 patients (20.4%)
      exposed only deformation of vertebral arteries with local increase of MFV and
      normal values in intracranial segments. Rotational tests were positive in 42
      (47.7%) patients and manifested high correlation with clinical data. EDS and TCCD
      are important tools for estimation of high hemodynamic risk in patients with PCD.
      Rotation induced vertebrobasilar ischemia with temporary impairment of cerebral
      blood flow to the brainstem, thalamus, and occipital lobes predicts possible
      posterior circulation TIA or stroke and helps with proper selection of further
      treatment strategy.

PMID- 24743119
TI  - Reversible cerebral vasoconstriction syndrome and migraine: sonography study.
AB  - RCVS is characterized by severe headaches with or without focal neurologic
      deficits and segmental constriction of cerebral arteries that resolves within 3
      months. The primary clinical manifestation is recurrent sudden-onset and
      thunderclap headache. Diagnosis requires cerebral or magnetic resonance
      angiography (MRA) confirmation and ultrasound monitoring. Our purpose is to
      discover the difference of ultrasound data between RCVS and migraine. 61 patients
      (age range 17-60y., 41-female, 20-male) underwent sonography examination using
      Transcranial Dopplerography (TCD) and Transcranial Color-Coded Duplex Sonography
      (TCCD) methods. In 29 patients MRA examinations were performed. Group I- 27
      patients with RCVS with typical acute-onset of severe headaches. Group II-34
      patients- migraine in anamnesis, with 1-2 attacks monthly, control group -15
      healthy persons. Ultrasound examinations were performed during 2 months with time
      intervals of 1-20, 21-40, and 41-60 days. Markedly in migraine group examinations
      were performed in interictal periods also. Group I-the mean maximum (MM) V(CS)
      77,8 +/- 14,7 cm/sec, V(MCA)- 127,5 +/- 22.8 cm/sec, V(ACA) -115.7 +/- 18.4,
      V(BA)- 74.7 +/- 20.1. Lindegaard Index (LI) -3.1 +/- 0.5. MRA revealed segmental
      cerebral artery vasoconstriction. The MCA was involved in 62.9%, the ACA- in
      51.8%, the PCA- in 37% and the BAS- in 40.7% of patients. Group II- the MM V (CS)
      72.8 +/- 12.5 cm/sec, V (MCA)- 118,4 +/- 26.7 cm/sec, V(ACA) -105.8 +/- 17.6,
      V(BA)- 74.5 +/- 18.1, averaged LI -2,9 +/- 0.7. In the majority (61.7%) of this
      group revealed increased MM V in several cerebral arteries with different
      combination of involving vessels. No correlation was found between incidence side
      of pain and /or pain intensity. Both groups exceeded of controls -V (MCA) (63.2
      +/- 9.5 cm/sec), LI (2.1 +/- 0.2), p<0.001) and revealed vasospasm. All data were
      calculated by nonparametric Binomial test. Obtained data showed no significant
      difference regarding the vasospasm degree between typical RCVS and migraine,
      whereas revealed that vasospasm in migraine is more determined to posterior
      circulation but in RCVS vasospasm has the more diffuse character. Despite the
      extensive knowledge concerning RCVS and migraine, many uncertainties still exist
      and further randomized controlled trials are needed for understanding the
      underlying pathophysiology factors.

PMID- 24743120
TI  - [Mechanisms of formation and progression of non-alcoholic fatty liver disease in
      type 2 diabetics].
AB  - Currently, study of the mechanisms of formation and progression of non-alcoholic
      fatty liver disease (NAFLD) in the patients with type 2 diabetes mellitus (DM) is
      a topical problem in endocrinology. Prognosis for the disease depends on NAFLD
      stage and it determines the necessity to study the origin and mostly the
      progression in NAFLD course. It will favour the enhancement of efficacy of the
      treatment for this cohort of patients. The object of this work was to study the
      mechanisms of formation of NAFLD phasic course in type 2 diabetics via
      determining the levels of lipid peroxidation (LPO), 8-isoprostaglandin as
      components of oxidative stress. LPO indices and liver functional activity
      parameters (general cholesterol, high-density lipoproteids cholesterol,
      triglycerides, beta-lipoproteids, very-low-density lipoproteids cholesterol,
      atherogenicity coefficient, thymol test, alanine aminotransferase, aspartate
      aminotransferase) were determined in the examined individuals. The carried
      research allowed, that changes in biochemical parameters levels is connected with
      increasing of diene conjugates (DC) activity and the carried correlation analysis
      of the studied values proved this relevance. The subgroup of the patients with DC
      levels of 200-400 nmol/l has no inflammatory alterations (cytolysis syndrome)
      that gives evidence of steatosis phase. The group of patients with DC levels of
      400-600 nmol/l demonstrated the stage of non-alcoholic steatohepatitis with the
      most expressed shifts in functional liver condition. The greatest lipid,
      carbohydrate metabolic changes were found in the subgroup of the patients with DC
      level of 600 nmol/l and more that gives evidence of fibrotic processes.

PMID- 24743121
TI  - [Structural and functional changes of heart and vessels in patients with
      essential hypertension and type 2 diabetes].
AB  - Comorbidity of essential hypertension and type 2 diabetes is a serious problem
      connected with early affection of target organs and further cardiovascular
      complications. Pathogenetic mechanisms, determining the progress of essential
      hypertension, insulin resistance and type 2 diabetes, mostly have mutual symptoms
      and lead to the progression of disease. Many investigators consider
      cardiovascular pathology to be disease which has free radical nature. Activation
      of free radical oxidative process and endothelial dysfunction are recognized one
      of the most important pathogenetic mechanisms of cardiovascular diseases. To
      investigate structural and functional changes of heart and vessels, state of the
      pro- and antioxidant status, levels of proinflammatory cytokines in patients with
      essential hypertension and type 2 diabetes we have examined 102 patients with
      essential hypertension stage II and type 2 diabetes in a moderate condition.
      After the investigation it was discovered that changes of cardiohemodynamics in
      patients with essential hypertension and type 2 diabetes are characterized by the
      following aspects: systolic function of left ventricle is conserved, concentric
      hypertrophy of left ventricle predominates and also there is diastolic
      dysfunction similar to disordered relaxation. Changes of blood vessel walls in
      the examined patients are shown by growing intima-media thickness and pulse wave
      velocity in carotid artery and aorta and also by dropping endothelium dependent
      vasodilation. The mentioned structural and functional changes in heart and
      magistral vessels go together with growing levels of cytokines, activation of pro
      oxidant system with suppression of antioxidant system, what is shown by
      correlation connections of different intention and direction.

PMID- 24743122
TI  - [Angioprotectors in the treatment of rosacea].
AB  - Rosacea - a common chronic inflammatory dermatosis (3-10% of all dermatoses)
      primarily affecting the skin of face. Numerous methods for the treatment of
      rosacea are defined by the diversity of etiologic and pathogenic factors of
      dermatosis, its stage and clinical form. But a significant role in its
      development, most researchers relate to vascular disturbances. It is suggested
      that vascular changes in this disease are the product of two interrelated
      pathological processes: the disturbances in integrity and tone of the vascular
      wall and disorganization of perivascular connective tissue. The results of these
      processes are formation of a stable dilatation of skin blood vessels clinically
      manifested by erythema and telangiectasia. Based on foregoing, The aim of this
      study was evaluation of therapeutic efficacy of Rutin Forte in complex treatment
      and prevention of rosacea. 30 patients with an erythematous stage of rosacea were
      under observation (20 women and 10 men) aged 25 to 50 years. The first group (15
      patients) was treated by the standard procedure (Antibiotics, systemic
      metronidazole, antihistamines, traditional external therapy). Patients of the
      second group (15 people) additionally received a Rutin Forte containing long
      acting vitamin C, zinc and selenium. The drug was administered at a dose of 2
      capsule per day. Duration of treatment - 2 to 3 months. Observation period after
      treatment were 12 months. During this period we revealed a significant reduction
      of erythema, recurrence of disease in the second group of patients was not
      observed, but in the group of comparison recurrences were detected on 3rd month
      of follow up and the degree of erythema reduction was significantly less. Thus,
      the study revealed that Rutin Forte is an effective means for the treatment and
      prevention of the torpid relapsing forms of rosacea on erythematous stage of
      dermatosis.

PMID- 24743123
TI  - [Analysis of spreading the sexually transmitted disorders in Georgia].
AB  - According statistical data in Georgia sexually transmitted disorders represent
      one of the most important medical and social problems. Main causes of this are
      hard social and economic condition of the country, changing sexual-behavioral
      stereotypes, drugs and alcohol abuse, political perturbation, as well as
      unprecedented decrease in financing prevention programs of STD by government. The
      purpose of given research is statistical analysis of spread of sexually
      transmitted disorders in Georgia, in particular, among the people included in
      risk group; finding trends and in accordance with this, working out
      recommendations for improvement of situation in given field of medicine. Essays
      showed that through 2000-2012 years among STD revealed in the group of increased
      risk chlamidiosis was the most common. There is an objective trend of increasing
      the level of morbidity with chlamidiosis and trichomoniasis, however the speed of
      increasing morbidity with trichomoniasis probably does not correspond the
      reality. In the same time morbidity with gonorrhea and syphilis is decreasing,
      however in the result of significant decrease in STD prevention program scale
      data validity concerning syphilis might be doubtful. Coming out of this in the
      field of health care related to STD optimization of laboratory diagnostics
      management is essential; perfection of methods of epidemiologic control;
      increasing the scales of prevention programs as well as initiation of researches
      related to antimicrobial resistance of gonococci. Authors consider essential
      taking steps for optimization of management of laboratory diagnostics and
      perfection of methods of epidemiologic control and increasing scales of
      preventive programs. 

PMID- 24743124
TI  - [Contribution of leptin in the development of insulin resistance in pregnant
      women with obesity].
AB  - The aim of the present study was to investigate contribution of leptin in the
      development of insulin resistance in obese pregnant women depending on the
      obesity class as well as its effect on the progression of pregnancy. 36 pregnant
      women of I and II obesity classes and 21 pregnant women with normal body mass
      participated in the study. Concentrations of insulin, leptin and C-reactive
      protein in blood serum were measured with immunoenzymatic assays. Insulin
      resistance (IR) was determined with the Caro index. Contribution of leptin to
      development of IR was assessed with the ratio "leptin/Caro index". An increase of
      leptin concentration in blood serum was found in pregnant women with obesity
      compared to healthy controls. Moreover, the ratio "leptin/Caro index" increased
      with IR progression and reached maximum in the group with obesity class II, where
      it was 5.8 times higher than in the control group. An increased frequency of
      gestoses and placentary dysfunction were manifestations of weakening of adaptive
      mechanisms of the organism associated with the IR progression and increased role
      of leptin in its development. Therefore, activation of adipocyte function through
      the increased leptin secretion and increased ratio "leptin/Caro index" reflects
      the important role of leptin in pathogenesis of IR in pregnant women with
      obesity. 

PMID- 24743125
TI  - [Leptospirosis in Georgia].
AB  - The aim of the article was to study epidemiological patterns of leptospirosis in
      Georgia from 2001 to 2011. The investigation revealed that formal registration of
      the infection began in 1950s. Single cases were reported annually in the country
      with the exception of 1986, when water-borne outbreak broke out in Sukhumi with
      21 detected cases. Low morbidity level of disease was reported during 2001-2005.
      Since 2006 significant increase of leptospirosis has been observed. The highest
      incidence was reported in 2011-1.81 per 100 000 population. The increase is
      likely to be mainly attributed to the improvements in diagnostics of the
      infection. Young and middle-age persons are more frequently vulnerable to
      leptospirosis in Georgia, 54.8% of the cases are reported among age group of 30
      59. Incidence of the infection is the highest in males - 60-65% of the detected
      cases. In addition, leptospirosis is characterized by high case-fatality rate -
      8.7 +/- 3.6% (95% CI=5.7-11.7). Case fatality is especially high in persons over
      60 and over reaching 24.3 +/- 8.1%. Only single cases are observed in children
      under 14. In 21st century ethiological structure of leptospirosis has being
      changed somehow. By contrast, in the earlier period the disease was mainly caused
      by L. icterohaemorrhagiae and L.grippotyphosa, nowadays we encounter such
      causative agents which were not observed in 20th century - L. autunnalis, L.
      mankarso, L. wolffii and others. Water is mainly implicated as a risk factor in
      the infection transmission. Finally, to study of epidemiological characteristics
      of leptospirosis in Georgia, identified that, the infection is widely distributed
      in the country, has an increasing tendency and duration of the disease frequently
      is a severe.

PMID- 24743126
TI  - [Mechanisms of development and clinical endoscopic characteristics of hp-negative
      gastropathy in patients with chronic heart failure].
AB  - Hp-negative gastropathies in chronic heart failure (CHF) are characterized with
      polyethiologic polymorphic changes of gastric mucosa (GM). At the same time the
      mechanisms of their development and peculiarities of clinical-endoscopic and
      morphological manifestations are understudied. The linkages of clinical and
      morphological changes of gastric mucosa with various factors, and, above all, the
      factors involved in the development and progression of heart failure, are needed
      to be studied fundamentally. Some of these factors are oxidative stress and lipid
      peroxidation, the enzyme activity of the antioxidant defense, immuno-inflammatory
      and vasoactive endothelial factors. The dependences between the mechanisms of
      development of Hp-negative gastropathies and CHF are understudied. Possible
      dependences between mechanisms of development of Hp-negative gastropathies and
      pathogenesis of main disease (hypertension), complicated by heart failure, are
      understudied also. It was revealed that the development of gastropathy in
      patients with hypertension of 2 degree and CHF was associated with depression
      disorders of lipid metabolism, activation of lipid peroxidation and decreased
      activity of enzymes of antioxidant protection. The predictors of macroscopic
      inflammatory changes of gastric mucosa in hypertensive patients with CHF and hp-
      negative gastropathies are atherogenic ratio, blood levels of diene conjugates,
      malondialdehyde and catalase. 

PMID- 24743127
TI  - [Prognosis of rotavirus infection in children].
AB  - The aim of the research was to develop the method for predicting the course of
      rotavirus gastroenteritis in children.Under the supervision were 3607 children
      aged from 9 days to 5 years with the diagnosis of "Acute gastroenteritis" and
      "Acute gastroenterocolitis". The diagnosis of rotavirus infection was on the
      basis of a set of clinical, epidemiological data and the results of para-clinical
      and bacteriological studies and data of detection of rotavirus antigen strain.
      Genotyping of rotavirus group A was performed by PCR 269 faecal samples. For
      rotavirus infection is characterized by the following clinical symptoms:
      intestinal disorders, symptoms of intoxication, signs of dehydration. Clinical
      manifestation of rotavirus infection is closely correlated with indicators of
      leukogram, erythrocyte sedimentation rate and the degree of metabolic acidosis.
      The presence of concomitant bacterial infection burden for rotavirus, but the
      presence of conditionally pathogenic flora practically did not influence on the
      clinical manifestation of the disease. The longest duration of diarrhea was
      observed in patients with rotavirus gastroenteritis was caused by a strain with
      genotype PCR they often occurred in children older than 2 years (t=3,4; p<0.01)).
      Special scheme has been developed for predicting the course of rotavirus
      gastroenteritis, including the availability of mix infection, to determine the
      severity of the pathological process a specially designed scale. 

PMID- 24743128
TI  - Expression pattern of DNA-methyltransferases and its health implication (short
      review).
AB  - Epigenetics is heritable and reversible alterations of gene expression without
      direct alteration of DNA sequences. One example of epigenetic factors is DNA
      methylation, which prevents certain genes from being expressed. Another example
      is histone modifications. In addition, miRNAs can silence genes at
      transcriptional and posttranscriptional level. DNA methylation is regulated by
      DNA methyltransferases (DNMT1, DNMT3a, and DNMT3b). Aberrant DNMTs expression is
      the dominant mechanism for the genome instability which associates with a wide
      range of diseases such as a cancer, autoimmune diseases, mental disorders. In
      this article we reviewed the major mechanisms of changes of DNA methylation
      regulated by DNMTs and the role of this changes in pathogenesis of various
      diseases. In addition we briefly reviewed epigenetic agents, such as inhibitors
      of DNA methyltransferases or HDAC (histone deacetylase) targeting oncology,
      hematology, immunology, and neurologic disease indications, and which are in
      various phases of study or have been clinically tested and approved by FDA (Food
      and Drug Administration).

PMID- 24743129
TI  - Features of CD44+/CD24-low phenotypic cell distribution in relation to predictive
      markers and molecular subtypes of invasive ductal carcinoma of the breast.
AB  - Breast cancer is the most widespread pathology among women. Despite the current
      progresses in research and treatment of metastatic breast cancer, mortality
      caused by this disease is still high, because above mentioned therapy is limited
      due to existence of cells resistant to therapy . Cancer stem cells are the only
      cells with ability of unlimited proliferative activity and cancerous potential,
      thus, they participate in the growth, progression and dissemination of cancer.
      Cancer stem cells are resistant to various forms of therapy, including
      chemotherapy and radiotherapy . Results of examination showed that 50% of all
      cases are positive on so called markers of stem cells, thus 45% of cases are
      negative. CD44+/CD24-low cases (cases that reveal stem cell-phenotype) in the
      group of invasive ductal carcinoma of Luminal A molecular subtype are almost as
      many as CD44+/CD24+ and CD44-/CD24+ phenotype cancers. In this group non-stem
      phenotype cases are 65%, so 5 times more than stem cell phenotype cancers. 1324
      postoperative breast materials studied through 2008-2012 at the laboratory of
      "Pathgeo-Union of Pathologists" LTD and Academician N. Kipshidze Central
      University Clinic were used as test materials and specimens from 393 patients
      with invasive ductal carcinoma were selected. CD44/CD24 markers' expression in
      phenotypically different cancers and clinic-pathologic parameters as well as
      various biological features was conducted by the Pearson's correlation analysis
      and using X2 test. Statistical analysis of obtained numeral data was held using
      SPSS V.19.0 program. Confidence interval of 95% was considered statistically
      significant. Stem cell phenotype positive cases are with the highest percentage
      represented in Luminal B and basal-like molecular subgroup that to our minds is
      associated with their aggressive behavior and resistance to chemotherapy.
      Relatively good prognosis and response to chemotherapy of Luminal A molecular
      subtype cancers are to be stipulated by lower percentage of cases with stem cells
      phenotype. With regard to the dimension of cancer the analysis of stem cell
      phenotype cancers showed that frequency of stem cell phenotype (CD44+/CD24-low)
      dramatically increases from T1 to T4 cancers. High density of stem cell phenotype
      cancers in cancers with metastatic lymphatic nodes proves that presence of
      mentioned phenotype plays a role in progression and dissemination. On the one
      hand, little amount of stem cells phenotype cancers (CD44+/CD24-low), on the
      other hand absence of negative cases for markers of stem cell in Her2 subtype
      makes us consider that come phenotype, close to stem-cell phenotype, plays the
      leading role in Her2 positive cases.

PMID- 24743130
TI  - [Parodontitis pathogenetic factors, their interaction and effects].
AB  - Induced by microbial intervention oxidative stress causes electronic transport
      disorder in gingival cells mitochondrias as well as decrease of energogenesis and
      increase of lipoperoxidation. In oral cavity local immunity is decreased in
      parodontitis, that is related with immunoglobulin A deficiency and lysozyme
      activity decrease. Against this background, microbial factors damaging effect on
      periodont is intensified. In parodontitis the free nitric oxide (NO) content
      decrease in gingival tissues and its appearance in saliva is related with
      transformation of NO into toxic peroxinitrite, that on its turn enhances
      oxidation, parodontal injury, cell degra dation and necrosis. Nitrooxide
      defficiency in gingival mucosal cells is characterized by decreased protein P-53
      expression and terminal differentiation disorder of the cells. Mitochodria
      related energogenesis disorder in gums causes inhibition of their cell
      regeneration, which together with apoptotic changes is characterized with
      parodontal tissue destruction and depletion. 

PMID- 24743131
TI  - [Bacterial phagelysates and malignant tumor growth].
AB  - Anti-tumor preventive efficacy of E.coli phagelysate has been studied.
      Investigations were conducted on 2-3 months 48 male mice. Regimen of preventive
      vaccinations were: single - 0,25 ml phagelysate intraperitoneal injection, 3 days
      before Ehrlich carcinoma inoculation (1x10(6) tumor cells); 3 times vaccinations
      (0,25 ml, with 3 day intervals) 3, 6, and 9 days before inoculation of carcinoma;
      and 10 times (during 10 days, before inoculation of carcinoma). Treatment
      efficacy was evaluated according to the indices of cancer growth (development of
      cancer tissue, cancer growth inhibition percent, lifespan and survival percent).
      Experiments have shown that single and 3 times preventive vaccinations inhibited
      tumor development and delayed malignant growth, while, 10 times permanent
      vaccinations had no effects on cancer growth. Cancer growth inhibition percent in
      single and 3 times vaccinated animals were 58% on the average. Maximal lifespan
      in control group mice consisted 59 days. By the 125th day of cancer growth, at
      single vaccination 17% of mice were alive, while in 3 times vaccinated mice the
      survival percent was 25%. Anti-tumor potential of E.coli pagelysate supposedly
      could be explained by immunoregulatory properties of the preparation.

PMID- 24743132
TI  - On the issues of implementation of the unified military medical electronic
      information network in the Republic of Armenia.
AB  - The article is based on literature reviews and personal observations on the
      medical service practice in the armed forces of the Republic of Armenia. It is
      declared that the military medical service in Armenia is an adequately
      functioning system, which guarantees the medical safety of the military service
      and could provide quality medical services to servicemen and other people equaled
      to servicemen entitled to free medical care prescribed by the legislation of the
      Republic of Armenia. However, the analysis showed that the means of uniform
      informational database and automatic control system are not actively used for
      patient's diagnosis and treatment; there is not the uniform informational
      database between medical service and the management of the armed forces. Thus,
      there is clearly a need to implement new information technologies to improve the
      management in unified military medical system. 

PMID- 24743133
TI  - Neurodevelopmental outcomes after hypothermia therapy in the era of Bayley-III.
AB  - OBJECTIVE: Bayley-III scales are currently used to evaluate outcomes of term
      infants following hypothermia therapy, while all before reported outcomes in this
      population have used Bayley-II. Our objectives were to determine the incidence of
      abnormal neurodevelopmental outcomes using Bayley III and the predictive value of
      Magnetic resonance imaging (MRI) in infants who received systemic hypothermia.
      STUDY DESIGN: We conducted a prospective cohort study of inborn infants who
      underwent hypothermia for moderate/severe neonatal encephalopathy from October
      2005-November 2011. RESULT: Eighty newborns underwent hypothermia (incidence of
      1/1000). Of the survivors, 89% had Bayley-III performed around 24 months of age.
      An abnormal outcome using Bayley-III <85 occurred in 50%, while Bayley III <70
      occurred in 13%. MRI predicted Bayley III<85 with sensitivity of 73%, specificity
      of 84%, positive-predictive value of 84% and negative-predictive value of 74%.
      CONCLUSION: A Bayley-III 85 cutoff identifies a disability rate of 50%, and MRI
      was predictive of abnormal outcomes. Findings can be useful for counseling of
      families and planning of future studies using Bayley III.

PMID- 24743134
TI  - Early feeding factors associated with exclusive versus partial human milk feeding
      in neonates receiving intensive care.
AB  - OBJECTIVE: To evaluate early feeding factors associated with exclusive human milk
      (EHM) feeding at discharge in a cohort of human milk-fed infants admitted to the
      neonatal intensive care unit (NICU). STUDY DESIGN: Retrospective cohort of
      consecutively discharged infants from two NICUs over a 12-month period who
      received any human milk during the 24 h before hospital discharge. We used
      logistic regression to evaluate early feeding factors associated with EHM feeding
      at discharge. RESULT: We evaluated a total of 264 infants. EHM-fed infants were
      twice as likely to receive human milk at the first feeding compared with partial
      human milk-fed infants (65% vs 32%; P<0.01). In multivariable analysis, including
      adjustment for race and type of maternal insurance, infants receiving human milk
      as the initial feeding, compared with formula, had a greater odds of EHM feeding
      at hospital discharge (adjusted odds ratio (OR)=3.41; 95% confidence interval
      (CI)=1.82 to 6.39; P<0.001). CONCLUSION: Among infants admitted to the NICU whose
      mothers provide human milk, those receiving human milk as the first feeding were
      more likely to receive EHM feeding at discharge.

PMID- 24743135
TI  - Effects of maternal iodine supplementation during pregnancy and lactation on
      iodine status and neonatal thyroid-stimulating hormone.
AB  - OBJECTIVE: To determine the iodine status in pregnant and lactating women, as
      well as neonatal thyroid-stimulating hormone (TSH) concentration. STUDY DESIGN:
      Pregnant women cared at our hospital, the University Hospital in Bangkok, had
      routinely received 200 MUg iodine tablet daily since October 2010. Urinary iodine
      concentrations (UICs) of 1508 pregnant and 87 lactating women and 76 offspring
      and breast milk iodine concentration (BMIC) (n=57) were measured. Cord serum TSH
      levels from hypothyroidism screening were analyzed. RESULT: Median UIC levels of
      pregnant and lactating women were 170.6 and 138.0 MUg l(-1), respectively. Median
      BMIC and infants' UIC at 2-month postpartum in iodine-supplemented group were
      higher than the respective values of non-supplemented group. Median cord serum
      TSH level obtained before iodine supplementation (n=8332) was higher than that
      obtained after supplementation (n=5181; 7.3 vs 5.2 mU l(-1)). CONCLUSION:
      Maternal iodine supplementation improved iodine nutrition in their breast-fed
      offspring. A trend toward declining in cord serum TSH values after iodine
      supplementation indicates improvement of iodine status during pregnancy.

PMID- 24743136
TI  - End-tidal carbon monoxide and hemolysis.
AB  - Hemolytic disease in newborns can result from a number of conditions, which can
      place such infants at an increased risk for the development of severe
      hyperbilirubinemia. Because the catabolism of heme produces equimolar amounts of
      carbon monoxide (CO) and bilirubin, measurements of end-tidal breath CO
      (corrected for ambient CO) or ETCOc can serve as an index of hemolysis as well as
      of bilirubin production from any cause. Elevated levels of ETCOc have been
      correlated with blood carboxyhemoglobin levels and thus hemolysis. However, the
      detection of hemolysis can be a clinically challenging problem in newborns. Here,
      we describe the importance of determining ETCOc levels and their application in
      identifying infants at risk for developing hyperbilirubinemia associated with
      hemolysis and other causes of increased bilirubin production. 

PMID- 24743138
TI  - Promising SINEs for embargoing nuclear-cytoplasmic export as an anticancer
      strategy.
AB  - In cancer cells, the nuclear-cytoplasmic transport machinery is frequently
      disrupted, resulting in mislocalization and loss of function for many key
      regulatory proteins. In this review, the mechanisms by which tumor cells co-opt
      the nuclear transport machinery to facilitate carcinogenesis, cell survival, drug
      resistance, and tumor progression will be elucidated, with a particular focus on
      the role of the nuclear-cytoplasmic export protein. The recent development of a
      new generation of selective inhibitors of nuclear export (XPO1 antagonists) and
      how these novel anticancer drugs may bring us closer to the implementation of
      this therapeutic strategy in the clinic will be discussed.

PMID- 24743137
TI  - Active trafficking of alpha 1 antitrypsin across the lung endothelium.
AB  - The homeostatic lung protective effects of alpha-1 antitrypsin (A1AT) may require
      the transport of circulating proteinase inhibitor across an intact lung
      endothelial barrier. We hypothesized that uninjured pulmonary endothelial cells
      transport A1AT to lung epithelial cells. Purified human A1AT was rapidly taken up
      by confluent primary rat pulmonary endothelial cell monolayers, was secreted
      extracellularly, both apically and basolaterally, and was taken up by adjacent
      rat lung epithelial cells co-cultured on polarized transwells. Similarly,
      polarized primary human lung epithelial cells took up basolaterally-, but not
      apically-supplied A1AT, followed by apical secretion. Evidence of A1AT
      transcytosis across lung microcirculation was confirmed in vivo by two-photon
      intravital microscopy in mice. Time-lapse confocal microscopy indicated that A1AT
      co-localized with Golgi in the endothelium whilst inhibition of the classical
      secretory pathway with tunicamycin significantly increased intracellular
      retention of A1AT. However, inhibition of Golgi secretion promoted non-classical
      A1AT secretion, associated with microparticle release. Polymerized A1AT or A1AT
      supplied to endothelial cells exposed to soluble cigarette smoke extract had
      decreased transcytosis. These results suggest previously unappreciated pathways
      of A1AT bidirectional uptake and secretion from lung endothelial cells towards
      the alveolar epithelium and airspaces. A1AT trafficking may determine its
      functional bioavailablity in the lung, which could be impaired in individuals
      exposed to smoking or in those with A1AT deficiency. 

PMID- 24743139
TI  - Second-Look Arthroscopic Evaluation of Cartilage Lesions After Mesenchymal Stem
      Cell Implantation in Osteoarthritic Knees.
AB  - BACKGROUND: Cartilage regenerative procedures have been receiving increased
      interest because of their potential to alter the progression of osteoarthritis
      (OA). The application of mesenchymal stem cells (MSCs) has been proposed as a new
      treatment option for OA based on the ability of these cells to differentiate into
      chondrocytes. PURPOSE: To investigate the clinical and second-look arthroscopic
      outcomes of MSC implantation and to identify prognostic factors associated with
      this treatment. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: This
      study retrospectively evaluated 37 knees examined using second-look arthroscopic
      surgery after MSC implantation for cartilage lesions in OA knees. Clinical
      outcomes were evaluated according to the International Knee Documentation
      Committee (IKDC) score and Tegner activity scale, and cartilage repair was
      assessed using International Cartilage Repair Society (ICRS) grading. Statistical
      analyses were performed to identify various prognostic factors associated with
      the clinical and second-look arthroscopic outcomes. RESULTS: The mean patient age
      was 57.4 years (range, 48-69 years), the mean follow-up period was 26.5 months
      (range, 24-34 months), the mean body mass index (BMI) was 26.3 kg/m2 (range, 19.8
      31.2 kg/m2), and the mean lesion size was 5.4 +/- 2.9 cm2 (range, 2.3-8.9 cm2).
      The mean IKDC and Tegner activity scale scores were significantly improved from
      38.0 +/- 7.8 to 61.0 +/- 11.0 and from 2.5 +/- 0.5 to 3.6 +/- 0.7, respectively
      (P < .001 for both). According to the ICRS overall repair grades at second-look
      arthroscopic surgery, 2 of the 37 lesions (5%) were grade I (normal), 7 (19%)
      were grade II (near normal), 20 (54%) were grade III (abnormal), and 8 (22%) were
      grade IV (severely abnormal). In terms of overall patient satisfaction with the
      operation, 33 (94%) patients reported good to excellent satisfaction. High BMI
      (>=27.5 kg/m2) and large lesion size (>=5.4 cm2) were found to be significant
      predictors of poor clinical and arthroscopic outcomes (P < .05 for both). Other
      prognostic factors, including patient age, sex, cartilage lesion location, and
      presence of subchondral cysts, did not significantly influence the outcomes (P >
      .05). CONCLUSION: The outcomes of MSC implantation for cartilage repair in OA
      knees seem encouraging; high BMI and large lesion size are important factors
      affecting outcomes. Although still in the early stages of application, MSC
      implantation for cartilage repair may have great potential for the treatment of
      OA knees. However, second-look arthroscopic findings revealed that 76% had the
      repair rated as abnormal or severely abnormal by ICRS standards. The development
      of an advanced surgical procedure with tissue-engineered scaffolds may be needed
      to treat patients with large cartilage lesions.

PMID- 24743140
TI  - The influence of spatiotemporal structure of noisy stimuli in decision making.
AB  - Decision making is a process of utmost importance in our daily lives, the study
      of which has been receiving notable attention for decades. Nevertheless, the
      neural mechanisms underlying decision making are still not fully understood.
      Computational modeling has revealed itself as a valuable asset to address some of
      the fundamental questions. Biophysically plausible models, in particular, are
      useful in bridging the different levels of description that experimental studies
      provide, from the neural spiking activity recorded at the cellular level to the
      performance reported at the behavioral level. In this article, we have reviewed
      some of the recent progress made in the understanding of the neural mechanisms
      that underlie decision making. We have performed a critical evaluation of the
      available results and address, from a computational perspective, aspects of both
      experimentation and modeling that so far have eluded comprehension. To guide the
      discussion, we have selected a central theme which revolves around the following
      question: how does the spatiotemporal structure of sensory stimuli affect the
      perceptual decision-making process? This question is a timely one as several
      issues that still remain unresolved stem from this central theme. These include:
      (i) the role of spatiotemporal input fluctuations in perceptual decision making,
      (ii) how to extend the current results and models derived from two-alternative
      choice studies to scenarios with multiple competing evidences, and (iii) to
      establish whether different types of spatiotemporal input fluctuations affect
      decision-making outcomes in distinctive ways. And although we have restricted our
      discussion mostly to visual decisions, our main conclusions are arguably
      generalizable; hence, their possible extension to other sensory modalities is one
      of the points in our discussion. 

PMID- 24743141
TI  - Repurposing staples for viruses: applying peptide design to RSV prophylaxis.
AB  - Respiratory syncytial virus (RSV) is responsible for lower respiratory tract
      infections and annually results in 200,000 deaths worldwide. Despite the burden
      of RSV-associated disease, treatments and preventative measures are limited. In
      this issue of JCI, Bird and colleagues describe their work using a peptide
      stapling technique that allowed synthesis of a stable peptide mimic of a portion
      of the RSV fusion protein. Pretreatment of cells with the stable peptide
      effectively blocked virus entry. When introduced into mice prior to RSV exposure,
      the peptide produced a substantial prophylactic effect. This work provides a new
      way forward in RSV prevention. 

PMID- 24743142
TI  - A VISTA on PD-1H.
AB  - Three years ago, two research groups independently identified a previously
      undescribed T cell cosignaling molecule; one referred to it as V-domain Ig
      suppressor of T cell activation (VISTA), and the other used the term programmed
      death-1 homolog (PD-1H). Recombinant and ectopically expressed PD-1H functions as
      a coinhibitory ligand for T cell responses. However, the function of endogenous
      PD-1H is not clear. In this issue of the JCI, Flies and colleagues demonstrate
      that endogenous PD-1H on both T cells and APCs serves as a coinhibitory molecule
      for T cell activation and provide further support for targeting PD-1H as a
      therapeutic strategy for transplantation and cancers. 

PMID- 24743143
TI  - Stargazing microRNA maps a new miR-21 star for cardiac hypertrophy.
AB  - Left ventricular hypertrophy is an initial compensatory mechanism in response to
      cardiac stress that can degenerate into heart failure and sudden cardiac death.
      Recent studies have shown that microRNAs (miRs) regulate several aspects of
      cardiovascular diseases. In this issue of the JCI, Bang and colleagues identified
      an exosome-mediated communication mechanism between cardiac fibroblasts and
      cardiomyocytes. Specifically, cardiac fibroblasts secrete miR-enriched exosomes,
      which are subsequently taken up by cardiomyocytes, in which they alter gene
      expression. In particular, a passenger strand miR, miR-21*, was identified as a
      potent paracrine factor that induces cardiomyocyte hypertrophy when shuttled
      through exosomes. These advanced comprehensive analyses represent a major step
      forward in our understanding of cardiovascular physiopathology, providing a
      promising adjunctive target for possible therapeutic approaches, namely the miR
      mediated paracrine signaling network. 

PMID- 24743144
TI  - Type 1 angiotensin receptors on macrophages ameliorate IL-1 receptor-mediated
      kidney fibrosis.
AB  - In a wide array of kidney diseases, type 1 angiotensin (AT1) receptors are
      present on the immune cells that infiltrate the renal interstitium. Here, we
      examined the actions of AT1 receptors on macrophages in progressive renal
      fibrosis and found that macrophage-specific AT1 receptor deficiency exacerbates
      kidney fibrosis induced by unilateral ureteral obstruction (UUO). Macrophages
      isolated from obstructed kidneys of mice lacking AT1 receptors solely on
      macrophages had heightened expression of proinflammatory M1 cytokines, including
      IL-1. Evaluation of isolated AT1 receptor-deficient macrophages confirmed the
      propensity of these cells to produce exaggerated levels of M1 cytokines, which
      led to more severe renal epithelial cell damage via IL-1 receptor activation in
      coculture compared with WT macrophages. A murine kidney crosstransplantation
      concomitant with UUO model revealed that augmentation of renal fibrosis
      instigated by AT1 receptor-deficient macrophages is mediated by IL-1 receptor
      stimulation in the kidney. This study indicates that a key role of AT1 receptors
      on macrophages is to protect the kidney from fibrosis by limiting activation of
      IL-1 receptors in the kidney. 

PMID- 24743145
TI  - Cardiac fibroblast-derived microRNA passenger strand-enriched exosomes mediate
      cardiomyocyte hypertrophy.
AB  - In response to stress, the heart undergoes extensive cardiac remodeling that
      results in cardiac fibrosis and pathological growth of cardiomyocytes
      (hypertrophy), which contribute to heart failure. Alterations in microRNA (miRNA)
      levels are associated with dysfunctional gene expression profiles associated with
      many cardiovascular disease conditions; however, miRNAs have emerged recently as
      paracrine signaling mediators. Thus, we investigated a potential paracrine miRNA
      crosstalk between cardiac fibroblasts and cardiomyocytes and found that cardiac
      fibroblasts secrete miRNA-enriched exosomes. Surprisingly, evaluation of the
      miRNA content of cardiac fibroblast-derived exosomes revealed a relatively high
      abundance of many miRNA passenger strands ("star" miRNAs), which normally undergo
      intracellular degradation. Using confocal imaging and coculture assays, we
      identified fibroblast exosomal-derived miR-21_3p (miR-21*) as a potent paracrine
      acting RNA molecule that induces cardiomyocyte hypertrophy. Proteome profiling
      identified sorbin and SH3 domain-containing protein 2 (SORBS2) and PDZ and LIM
      domain 5 (PDLIM5) as miR-21* targets, and silencing SORBS2 or PDLIM5 in
      cardiomyocytes induced hypertrophy. Pharmacological inhibition of miR-21* in a
      mouse model of Ang II-induced cardiac hypertrophy attenuated pathology. These
      findings demonstrate that cardiac fibroblasts secrete star miRNA-enriched
      exosomes and identify fibroblast-derived miR-21* as a paracrine signaling
      mediator of cardiomyocyte hypertrophy that has potential as a therapeutic target.

PMID- 24743146
TI  - Monocytes expressing CX3CR1 orchestrate the development of vincristine-induced
      pain.
AB  - A major dose-limiting side effect associated with cancer-treating antineoplastic
      drugs is the development of neuropathic pain, which is not readily relieved by
      available analgesics. A better understanding of the mechanisms that underlie pain
      generation has potential to provide targets for prophylactic management of
      chemotherapy pain. Here, we delineate a pathway for pain that is induced by the
      chemotherapeutic drug vincristine sulfate (VCR). In a murine model of
      chemotherapy-induced allodynia, VCR treatment induced upregulation of endothelial
      cell adhesion properties, resulting in the infiltration of circulating CX3CR1+
      monocytes into the sciatic nerve. At the endothelial-nerve interface, CX3CR1+
      monocytes were activated by the chemokine CX3CL1 (also known as fractalkine
      [FKN]), which promoted production of reactive oxygen species that in turn
      activated the receptor TRPA1 in sensory neurons and evoked the pain response.
      Furthermore, mice lacking CX3CR1 exhibited a delay in the development of
      allodynia following VCR administration. Together, our data suggest that CX3CR1
      antagonists and inhibition of FKN proteolytic shedding, possibly by targeting
      ADAM10/17 and/or cathepsin S, have potential as peripheral approaches for the
      prophylactic treatment of chemotherapy-induced pain.

PMID- 24743147
TI  - Mucosal delivery of a double-stapled RSV peptide prevents nasopulmonary
      infection.
AB  - Respiratory syncytial virus (RSV) infection accounts for approximately 64 million
      cases of respiratory disease and 200,000 deaths worldwide each year, yet no
      broadly effective prophylactic or treatment regimen is available. RSV deploys
      paired, self-associating, heptad repeat domains of its fusion protein, RSV-F, to
      form a fusogenic 6-helix bundle that enables the virus to penetrate the host cell
      membrane. Here, we developed hydrocarbon double-stapled RSV fusion peptides that
      exhibit stabilized alpha-helical structure and striking proteolytic resistance.
      Pretreatment with double-stapled RSV peptides that specifically bound to the RSV
      fusion bundle inhibited infection by both laboratory and clinical RSV isolates in
      cells and murine infection models. Intranasal delivery of a lead double-stapled
      RSV peptide effectively prevented viral infection of the nares. A chitosan-based
      nanoparticle preparation markedly enhanced pulmonary delivery, further preventing
      progression of RSV infection to the lung. Thus, our results provide a strategy
      for inhibiting RSV infection by mucosal and endotracheal delivery of double
      stapled RSV fusion peptides. 

PMID- 24743148
TI  - Multifactorial ERbeta and NOTCH1 control of squamous differentiation and cancer.
AB  - Downmodulation or loss-of-function mutations of the gene encoding NOTCH1 are
      associated with dysfunctional squamous cell differentiation and development of
      squamous cell carcinoma (SCC) in skin and internal organs. While NOTCH1 receptor
      activation has been well characterized, little is known about how NOTCH1 gene
      transcription is regulated. Using bioinformatics and functional screening
      approaches, we identified several regulators of the NOTCH1 gene in keratinocytes,
      with the transcription factors DLX5 and EGR3 and estrogen receptor beta (ERbeta)
      directly controlling its expression in differentiation. DLX5 and ERG3 are
      required for RNA polymerase II (PolII) recruitment to the NOTCH1 locus, while
      ERbeta controls NOTCH1 transcription through RNA PolII pause release. Expression
      of several identified NOTCH1 regulators, including ERbeta, is frequently
      compromised in skin, head and neck, and lung SCCs and SCC-derived cell lines.
      Furthermore, a keratinocyte ERbeta-dependent program of gene expression is
      subverted in SCCs from various body sites, and there are consistent differences
      in mutation and gene-expression signatures of head and neck and lung SCCs in
      female versus male patients. Experimentally increased ERbeta expression or
      treatment with ERbeta agonists inhibited proliferation of SCC cells and promoted
      NOTCH1 expression and squamous differentiation both in vitro and in mouse
      xenotransplants. Our data identify a link between transcriptional control of
      NOTCH1 expression and the estrogen response in keratinocytes, with implications
      for differentiation therapy of squamous cancer. 

PMID- 24743149
TI  - Efficient phagocytosis and laccase activity affect the outcome of HIV-associated
      cryptococcosis.
AB  - BACKGROUND: Cryptococcal meningitis (CM) is a leading cause of HIV-associated
      mortality globally. High fungal burden in cerebrospinal fluid (CSF) at diagnosis
      and poor fungal clearance during treatment are recognized adverse prognostic
      markers; however, the underlying pathogenic factors that drive these clinical
      manifestations are incompletely understood. We profiled a large set of clinical
      isolates for established cryptococcal virulence traits to evaluate the
      contribution of C. neoformans phenotypic diversity to clinical presentation and
      outcome in human cryptococcosis. METHODS: Sixty-five C. neoformans isolates from
      clinical trial patients with matched clinical data were assayed in vitro to
      determine murine macrophage uptake, intracellular proliferation rate (IPR),
      capsule induction, and laccase activity. Analysis of the correlation between
      prognostic clinical and host immune parameters and fungal phenotypes was
      performed using Spearman's r, while the fungal-dependent impact on long-term
      survival was determined by Cox regression analysis. RESULTS: High levels of
      fungal uptake by macrophages in vitro, but not the IPR, were associated with CSF
      fungal burden (r = 0.38, P = 0.002) and long-term patient survival (hazard ratio
      [HR] 2.6, 95% CI 1.2-5.5, P = 0.012). High-uptake strains were hypocapsular (r = 
      0.28, P = 0.05) and exhibited enhanced laccase activity (r = 0.36, P = 0.003).
      Fungal isolates with greater laccase activity exhibited heightened survival ex
      vivo in purified CSF (r = 0.49, P < 0.0001) and resistance to clearance following
      patient antifungal treatment (r = 0.39, P = 0.003). CONCLUSION: These findings
      underscore the contribution of cryptococcal-phagocyte interactions and laccase
      dependent melanin pathways to human clinical presentation and outcome.
      Furthermore, characterization of fungal-specific pathways that drive clinical
      manifestation provide potential targets for the development of therapeutics and
      the management of CM. FUNDING: This work was made possible by funding from the
      Wellcome Trust (WT088148MF), the Medical Research Council (MR/J008176/1), the
      NIHR Surgical Reconstruction and Microbiology Research Centre and the Lister
      Institute for Preventive Medicine (to R.C. May), and a Wellcome Trust
      Intermediate fellowship (089966, to T. Bicanic). The C. neoformans isolates were
      collected within clinical trials funded by the British Infection Society
      (fellowship to T. Bicanic), the Wellcome Trust (research training fellowships
      WT069991, to A.E. Brouwer and WT081794, to J.N. Jarvis), and the Medical Research
      Council, United Kingdom (76201). The funding sources had no role in the design or
      conduct of this study, nor in preparation of the manuscript.

PMID- 24743150
TI  - Coinhibitory receptor PD-1H preferentially suppresses CD4+ T cell-mediated
      immunity.
AB  - T cell activation is regulated by the interactions of surface receptors with
      stimulatory and inhibitory ligands. Programmed death-1 homolog (PD-1H, also
      called VISTA) is a member of the CD28 family of proteins and has been shown to
      act as a coinhibitory ligand on APCs that suppress T cell responses. Here, we
      determined that PD-1H functions as a coinhibitory receptor for CD4+ T cells. CD4+
      T cells in mice lacking PD-1H exhibited a dramatically increased response to
      antigen stimulation. Furthermore, delivery of a PD-1H-specific agonist mAb
      directly inhibited CD4+ T cell activation both in vitro and in vivo, validating a
      coinhibitory function of PD-1H. In a murine model of acute hepatitis,
      administration of a PD-1H agonist mAb suppressed CD4+ T cell-mediated acute
      inflammation. PD-1H-deficient animals were highly resistant to tumor induction in
      a murine brain glioma model, and depletion of CD4+ T cells, but not CD8+ T cells,
      promoted tumor formation. Together, our findings suggest that PD-1H has potential
      as a target of immune modulation in the treatment of human inflammation and
      malignancies.

PMID- 24743152
TI  - Cryptococcosis: a model for the understanding of infectious diseases.
AB  - The increase in immunosuppressed patient populations has correlated with a rise
      in clinical fungal infections, including cryptococcosis. Patient outcome
      following Cryptococcus infection is linked to initial fungal burden in
      cerebrospinal fluid (CSF) and fungal clearance following treatment; however, the
      role of the pathogen in disease prognosis is poorly defined. In this issue of the
      JCI, Sabiiti and colleagues have directly correlated phenotypic traits of
      Cryptococcus neoformans with clinical outcome of infected patients. A better
      understanding of both the host and pathogen contributions to disease etiology
      will provide more options for targeted treatment strategies. 

PMID- 24743151
TI  - Apolipoprotein O is mitochondrial and promotes lipotoxicity in heart.
AB  - Diabetic cardiomyopathy is a secondary complication of diabetes with an unclear
      etiology. Based on a functional genomic evaluation of obesity-associated cardiac
      gene expression, we previously identified and cloned the gene encoding
      apolipoprotein O (APOO), which is overexpressed in hearts from diabetic patients.
      Here, we generated APOO-Tg mice, transgenic mouse lines that expresses
      physiological levels of human APOO in heart tissue. APOO-Tg mice fed a high-fat
      diet exhibited depressed ventricular function with reduced fractional shortening
      and ejection fraction, and myocardial sections from APOO-Tg mice revealed
      mitochondrial degenerative changes. In vivo fluorescent labeling and subcellular
      fractionation revealed that APOO localizes with mitochondria. Furthermore, APOO
      enhanced mitochondrial uncoupling and respiration, both of which were reduced by
      deletion of the N-terminus and by targeted knockdown of APOO. Consequently, fatty
      acid metabolism and ROS production were enhanced, leading to increased AMPK
      phosphorylation and Ppara and Pgc1a expression. Finally, we demonstrated that the
      APOO-induced cascade of events generates a mitochondrial metabolic sink whereby
      accumulation of lipotoxic byproducts leads to lipoapoptosis, loss of cardiac
      cells, and cardiomyopathy, mimicking the diabetic heart-associated metabolic
      phenotypes. Our data suggest that APOO represents a link between impaired
      mitochondrial function and cardiomyopathy onset, and targeting APOO-dependent
      metabolic remodeling has potential as a strategy to adjust heart metabolism and
      protect the myocardium from impaired contractility. 

PMID- 24743153
TI  - Detection of lung tumors in mice using a 1-tesla compact magnetic resonance
      imaging system.
AB  - Due to their small size, lung tumors in rodents are typically investigated using
      high-field magnetic resonance (MR) systems (4.7 T or higher) to achieve higher
      signal-to-noise ratios, although low-field MR systems are less sensitive to
      susceptibility artifacts caused by air in the lung. We investigated the
      feasibility of detecting lung tumors in living, freely breathing mice with a 1-T
      compact permanent magnet MR system. In total, 4 mice were used, and MR images of
      mouse lungs were acquired using a T1-weighted three-dimensional fast low-angle
      shot sequence without cardiac or respiratory gating. The delineation and size of
      lung tumors were assessed and compared with histopathological findings.
      Submillimeter lesions were demonstrated as hyperintense, relative to the
      surrounding lung parenchyma, and were delineated clearly. Among the 13 lesions
      validated in histopathological sections, 11 were detected in MR images; the MR
      detection rate was thus 84.6%. A strong correlation was obtained in size
      measurements between MR images and histological sections. Thus, a dedicated low
      field MR system can be used to detect lung tumors in living mice noninvasively
      without gating. 

PMID- 24743154
TI  - Functional substitution of a eukaryotic glycyl-tRNA synthetase with an
      evolutionarily unrelated bacterial cognate enzyme.
AB  - Two oligomeric types of glycyl-tRNA synthetase (GlyRS) are found in nature: a
      alpha2 type and a alpha2beta2 type. The former has been identified in all three
      kingdoms of life and often pairs with tRNAGly that carries an A73 discriminator
      base, while the latter is found only in bacteria and chloroplasts and is almost
      always coupled with tRNAGly that contains U73. In the yeast Saccharomyces
      cerevisiae, a single GlyRS gene, GRS1, provides both the cytoplasmic and
      mitochondrial functions, and tRNAGly isoacceptors in both compartments possess
      A73. We showed herein that Homo sapiens and Arabidopsis thaliana cytoplasmic
      GlyRSs (both alpha2-type enzymes) can rescue both the cytoplasmic and
      mitochondrial defects of a yeast grs1- strain, while Escherichia coli GlyRS (a
      alpha2beta2-type enzyme) and A. thaliana organellar GlyRS (a (alphabeta)2-type
      enzyme) failed to rescue either defect of the yeast mull allele. However, a head
      to-tail alphabeta fusion of E. coli GlyRS effectively supported the mitochondrial
      function. Our study suggests that a alpha2-type eukaryotic GlyRS may be
      functionally substituted with a alpha2beta2-type bacterial cognate enzyme despite
      their remote evolutionary relationships. 

PMID- 24743156
TI  - Design of a broadband electrical impedance matching network for piezoelectric
      ultrasound transducers based on a genetic algorithm.
AB  - An improved method based on a genetic algorithm (GA) is developed to design a
      broadband electrical impedance matching network for piezoelectric ultrasound
      transducer. A key feature of the new method is that it can optimize both the
      topology of the matching network and perform optimization on the components. The
      main idea of this method is to find the optimal matching network in a set of
      candidate topologies. Some successful experiences of classical algorithms are
      absorbed to limit the size of the set of candidate topologies and greatly
      simplify the calculation process. Both binary-coded GA and real-coded GA are used
      for topology optimization and components optimization, respectively. Some
      calculation strategies, such as elitist strategy and clearing niche method, are
      adopted to make sure that the algorithm can converge to the global optimal
      result. Simulation and experimental results prove that matching networks with
      better performance might be achieved by this improved method. 

PMID- 24743155
TI  - A cross sectional analysis of the role of the antimicrobial peptide cathelicidin
      in lung function impairment within the ALIVE cohort.
AB  - BACKGROUND: Vitamin D deficiency is associated with reduced lung function.
      Cathelicidin, an antimicrobial peptide regulated by vitamin D, plays a role
      within the innate immune system. The association of cathelicidin with lung
      function decrement and respiratory infection is undefined. We determined the
      independent relationship of cathelicidin with lung function. METHODS: In a cross
      sectional analysis of 650 participants in an urban observational cohort with high
      smoking prevalence, plasma 25(OH)-vitamin D and cathelicidin levels were measured
      from stored samples obtained within 6 months of spirometry study visits.
      Multivariable linear regression was used to determine the independent association
      between low cathelicidin (defined as the lowest quartile of the cohort) and
      absolute forced expiratory volume in 1 second (FEV1). RESULTS: The mean age of
      the cohort was 49 years; 91% were black, 35% female and 41% HIV-infected.
      Participants with low cathelicidin had a 183 mL lower FEV1 compared to higher
      cathelicidin (p = 0.009); this relationship was maintained (115 ml lower; p =
      0.035) after adjusting for demographics, BMI, and smoking. Neither HIV
      serostatus, heavy smoking history, nor 25(OH)-vitamin D levels were associated
      with cathelicidin levels. Participants with low cathelicidin had a greater
      prevalence of prior bacterial pneumonia (21% versus 14%; p = 0.047). Inclusion of
      pneumonia in adjusted models did not substantially reduce the FEV1 decrement
      observed with low cathelicidin (104 mL lower FEV1; p = 0.05). Lung function
      decrements associated with low cathelicidin were greatest among individuals with
      lower 25(OH)-vitamin D levels. CONCLUSIONS: In a cohort at risk for airflow
      obstruction, low cathelicidin was independently associated with lower FEV1. These
      clinical data support a mechanistic link between 25(OH)-vitamin D deficiency and
      lung function impairment, independent of pneumonia risk.

PMID- 24743157
TI  - Response mechanism for surface acoustic wave gas sensors based on surface
      adsorption.
AB  - A theoretical model is established to describe the response mechanism of surface
      acoustic wave (SAW) gas sensors based on physical adsorption on the detector
      surface. Wohljent's method is utilized to describe the relationship of sensor
      output (frequency shift of SAW oscillator) and the mass loaded on the detector
      surface. The Brunauer-Emmett-Teller (BET) formula and its improved form are
      introduced to depict the adsorption behavior of gas on the detector surface. By
      combining the two methods, we obtain a theoretical model for the response
      mechanism of SAW gas sensors. By using a commercial SAW gas chromatography (GC)
      analyzer, an experiment is performed to measure the frequency shifts caused by
      different concentration of dimethyl methylphosphonate (DMMP). The parameters in
      the model are given by fitting the experimental results and the theoretical curve
      agrees well with the experimental data. 

PMID- 24743158
TI  - Integration of fiber-optic sensor arrays into a multi-modal tactile sensor
      processing system for robotic end-effectors.
AB  - With the increasing complexity of robotic missions and the development towards
      long-term autonomous systems, the need for multi-modal sensing of the environment
      increases. Until now, the use of tactile sensor systems has been mostly based on
      sensing one modality of forces in the robotic end-effector. The use of a multi
      modal tactile sensory system is motivated, which combines static and dynamic
      force sensor arrays together with an absolute force measurement system. This
      publication is focused on the development of a compact sensor interface for a
      fiber-optic sensor array, as optic measurement principles tend to have a bulky
      interface. Mechanical, electrical and software approaches are combined to realize
      an integrated structure that provides decentralized data pre-processing of the
      tactile measurements. Local behaviors are implemented using this setup to show
      the effectiveness of this approach. 

PMID- 24743159
TI  - Enhance the pyroelectricity of polyvinylidene fluoride by graphene-oxide doping.
AB  - The high quality properties and benefits of graphene-oxide have generated an
      active area of research where many investigations have shown potential
      applications in various technological fields. This paper proposes a methodology
      for enhancing the pyro-electricity of PVDF by graphene-oxide doping. The PVDF
      film with graphene-oxide is prepared by the sol-gel method. Firstly, PVDF and
      graphene-oxide powders are dispersed into dimethylformamide as solvent to form a
      sol solution. Secondly, the sol solution is deposited on a flexible ITO/PET
      substrate by spin-coating. Thirdly, the particles in the sol solution are
      polymerized through baking off the solvent to produce a gel in a state of a
      continuous network of PVDF and graphene-oxide. The final annealing process
      pyrolyzes the gel and form a beta-phase PVDF film with graphene-oxide doping. A
      complete study on the process of the graphene oxide doping of PVDF is
      accomplished. Some key points about the process are addressed based on
      experiments. The solutions to some key issues are found in this work, such as the
      porosity of film, the annealing temperature limitation by the use of flexible PET
      substrate, and the concentrations of PVDF and graphene-oxide. 

PMID- 24743160
TI  - IMU-based joint angle measurement for gait analysis.
AB  - This contribution is concerned with joint angle calculation based on inertial
      measurement data in the context of human motion analysis. Unlike most robotic
      devices, the human body lacks even surfaces and right angles. Therefore, we focus
      on methods that avoid assuming certain orientations in which the sensors are
      mounted with respect to the body segments. After a review of available methods
      that may cope with this challenge, we present a set of new methods for: (1) joint
      axis and position identification; and (2) flexion/extension joint angle
      measurement. In particular, we propose methods that use only gyroscopes and
      accelerometers and, therefore, do not rely on a homogeneous magnetic field. We
      provide results from gait trials of a transfemoral amputee in which we compare
      the inertial measurement unit (IMU)-based methods to an optical 3D motion capture
      system. Unlike most authors, we place the optical markers on anatomical landmarks
      instead of attaching them to the IMUs. Root mean square errors of the knee
      flexion/extension angles are found to be less than 1 degrees  on the prosthesis
      and about 3 degrees  on the human leg. For the plantar/dorsiflexion of the ankle,
      both deviations are about 1 degrees . 

PMID- 24743161
TI  - Recombinant paracoccin reproduces the biological properties of the native protein
      and induces protective Th1 immunity against Paracoccidioides brasiliensis
      infection.
AB  - BACKGROUND: Paracoccin is a dual-function protein of the yeast Paracoccidioides
      brasiliensis that has lectin properties and N-acetylglucosaminidase activities.
      Proteomic analysis of a paracoccin preparation from P. brasiliensis revealed that
      the sequence matched that of the hypothetical protein encoded by PADG-3347 of
      isolate Pb-18, with a polypeptide sequence similar to the family 18
      endochitinases. These endochitinases are multi-functional proteins, with distinct
      lectin and enzymatic domains. METHODOLOGY/PRINCIPAL FINDINGS: The multi-exon
      assembly and the largest exon of the predicted ORF (PADG-3347), was cloned and
      expressed in Escherichia coli cells, and the features of the recombinant proteins
      were compared to those of the native paracoccin. The multi-exon protein was also
      used for protection assays in a mouse model of paracoccidioidomycosis.
      CONCLUSIONS/SIGNIFICANCE: Our results showed that the recombinant protein
      reproduced the biological properties described for the native protein-including
      binding to laminin in a manner that is dependent on carbohydrate recognition
      showed N-acetylglucosaminidase activity, and stimulated murine peritoneal
      macrophages to produce high levels of TNF-alpha and nitric oxide. Considering the
      immunomodulatory potential of glycan-binding proteins, we also investigated
      whether prophylactic administration of recombinant paracoccin affected the course
      of experimental paracoccidioidomycosis in mice. In comparison to animals injected
      with vehicle (controls), mice treated with recombinant paracoccin displayed lower
      pulmonary fungal burdens and reduced pulmonary granulomas. These protective
      effects were associated with augmented pulmonary levels of IL-12 and IFN-gamma.
      We also observed that injection of paracoccin three days before challenge was the
      most efficient administration protocol, as the induced Th1 immunity was balanced
      by high levels of pulmonary IL-10, which may prevent the tissue damage caused by
      exacerbated inflammation. The results indicated that paracoccin is the protein
      encoded by PADG-3347, and we propose that this gene and homologous proteins in
      other P. brasiliensis strains be called paracoccin. We also concluded that
      recombinant paracoccin confers resistance to murine P. brasiliensis infection by
      exerting immunomodulatory effects.

PMID- 24743162
TI  - Impact of hypertension on the association of BMI with risk and age at onset of
      type 2 diabetes mellitus: age- and gender-mediated modifications.
AB  - AIMS: Given that BMI correlates with risk of Type 2 diabetes mellitus (T2DM), and
      that hypertension is a common comorbid condition, we hypothesize that
      hypertension augments significantly the impact of obesity on T2DM onset. METHODS:
      We obtained data on T2DM in Kuwaiti natives from Kuwait Health Network Registry.
      We considered 1339 comorbid individuals with onset of hypertension preceding that
      of T2DM, and 3496 non-hypertensive individuals but with T2DM. Multiple linear
      regressions, ANOVA tests, and Cox proportional hazards models were used to
      quantify the impact of hypertension on correlation of BMI with age at onset and
      risk of T2DM. RESULTS: Impact of increasing levels of BMI on age at onset ot T2DM
      is seen augmented in patients diagnosed with hypertension. We find that the slope
      of the inverse linear relationship between BMI and onset age of T2DM is much
      steep in hypertensive patients (-0.69, males and -0.39, females) than in non
      hypertensive patients (-0.36, males and -0.17, females). The decline in onset age
      for an unit increase of BMI is two-fold in males than in females. Upon
      considering BMI as a categorical variable, we find that while the mean onset age
      of T2DM in hypertensive patients decreases by as much as 5-12 years in every
      higher BMI categories, significant decrease in non-hypertensive patients exists
      only when severely obese. Hazard due to hypertension (against the baseline of non
      hypertension and normal weight) increases at least two-fold in every obese
      category. While males have higher hazard due to hypertension in early adulthood,
      females have higher hazard in late adulthood. CONCLUSION: Pre-existing condition
      of hypertension augments the association of BMI with Type 2 diabetes onset in
      both males and females. The presented results provide health professionals
      directives on the extent of weight-loss required to delay onset of Type 2
      diabetes in hypertensive versus non-hypertensive patients.

PMID- 24743163
TI  - Preprocedural fasting for coronary interventions: is it time to change practice?

PMID- 24743165
TI  - An optimized ERP brain-computer interface based on facial expression changes.
AB  - OBJECTIVE: Interferences from spatially adjacent non-target stimuli are known to
      evoke event-related potentials (ERPs) during non-target flashes and, therefore,
      lead to false positives. This phenomenon was commonly seen in visual attention
      based brain-computer interfaces (BCIs) using conspicuous stimuli and is known to
      adversely affect the performance of BCI systems. Although users try to focus on
      the target stimulus, they cannot help but be affected by conspicuous changes of
      the stimuli (such as flashes or presenting images) which were adjacent to the
      target stimulus. Furthermore, subjects have reported that conspicuous stimuli
      made them tired and annoyed. In view of this, the aim of this study was to reduce
      adjacent interference, annoyance and fatigue using a new stimulus presentation
      pattern based upon facial expression changes. Our goal was not to design a new
      pattern which could evoke larger ERPs than the face pattern, but to design a new
      pattern which could reduce adjacent interference, annoyance and fatigue, and
      evoke ERPs as good as those observed during the face pattern. APPROACH: Positive
      facial expressions could be changed to negative facial expressions by minor
      changes to the original facial image. Although the changes are minor, the
      contrast is big enough to evoke strong ERPs. In this paper, a facial expression
      change pattern between positive and negative facial expressions was used to
      attempt to minimize interference effects. This was compared against two different
      conditions, a shuffled pattern containing the same shapes and colours as the
      facial expression change pattern, but without the semantic content associated
      with a change in expression, and a face versus no face pattern. Comparisons were
      made in terms of classification accuracy and information transfer rate as well as
      user supplied subjective measures. MAIN RESULTS: The results showed that
      interferences from adjacent stimuli, annoyance and the fatigue experienced by the
      subjects could be reduced significantly (p < 0.05) by using the facial expression
      change patterns in comparison with the face pattern. The offline results show
      that the classification accuracy of the facial expression change pattern was
      significantly better than that of the shuffled pattern (p < 0.05) and the face
      pattern (p < 0.05). SIGNIFICANCE: The facial expression change pattern presented
      in this paper reduced interference from adjacent stimuli and decreased the
      fatigue and annoyance experienced by BCI users significantly (p < 0.05) compared
      to the face pattern.

PMID- 24743164
TI  - Contemporary aetiology, clinical characteristics and prognosis of adults with
      heart failure observed in a tertiary hospital in Tanzania: the prospective
      Tanzania Heart Failure (TaHeF) study.
AB  - OBJECTIVE: This study aimed to describe the contemporary aetiology, clinical
      characteristics and mortality and its predictors in heart failure (HF) in
      Tanzania. METHODS: Design; Prospective observational study. Setting;
      Cardiovascular Center of the Muhimbili National Hospital in Dar es Salaam,
      Tanzania. Patients >=18 years of age with HF defined by the Framingham criteria.
      MAIN OUTCOME MEASURE: All-cause mortality. RESULTS: Among 427 included patients,
      217 (51%) were females and the mean (SD) age was 55 (17) years. HF aetiologies
      included hypertension (45%), cardiomyopathy (28%), rheumatic heart disease (RHD)
      (12%) and ischaemic heart disease (9%). Concurrent atrial fibrillation (AF),
      clinically significant anaemia, diabetes, tuberculosis and HIV were found in 16%,
      12%, 12%, 3% and 2%, respectively, while warfarin was used in 3% of the patients.
      The mortality rate, 22.4 per 100 person-years over a median follow-up of 7
      months, was independently associated with AF, HR 3.4 (95% CI 1.6 to 7.0); in
      patient 3.2 (1.5 to 6.8); anaemia 2.3 (1.2 to 4.5); pulmonary hypertension 2.1
      (1.1 to 4.2) creatinine clearance 0.98 (0.97 to 1.00) and lack of education 2.3
      (1.3 to 4.2). CONCLUSIONS: In HF in Tanzania, patients are younger than in the
      developed world, but aetiologies are becoming more similar, with hypertension
      becoming more and RHD less important. Predictors of mortality possible to
      intervene against are anaemia, AF and lack of education.

PMID- 24743166
TI  - Unravelling the microbiome of eggs of the endangered sea turtle Eretmochelys
      imbricata identifies bacteria with activity against the emerging pathogen
      Fusarium falciforme.
AB  - Habitat bioaugmentation and introduction of protective microbiota have been
      proposed as potential conservation strategies to rescue endangered mammals and
      amphibians from emerging diseases. For both strategies, insight into the
      microbiomes of the endangered species and their habitats is essential. Here, we
      sampled nests of the endangered sea turtle species Eretmochelys imbricata that
      were infected with the fungal pathogen Fusarium falciforme. Metagenomic analysis
      of the bacterial communities associated with the shells of the sea turtle eggs
      revealed approximately 16,664 operational taxonomic units, with Proteobacteria,
      Actinobacteria, Firmicutes and Bacteroidetes as the most dominant phyla.
      Subsequent isolation of Actinobacteria from the eggshells led to the
      identification of several genera (Streptomyces, Amycolaptosis, Micromomospora
      Plantactinospora and Solwaraspora) that inhibit hyphal growth of the pathogen F.
      falciforme. These bacterial genera constitute a first set of microbial indicators
      to evaluate the potential role of microbiota in conservation of endangered sea
      turtle species. 

PMID- 24743167
TI  - Transamidase subunit GAA1/GPAA1 is a M28 family metallo-peptide-synthetase that
      catalyzes the peptide bond formation between the substrate protein's omega-site
      and the GPI lipid anchor's phosphoethanolamine.
AB  - The transamidase subunit GAA1/GPAA1 is predicted to be the enzyme that catalyzes
      the attachment of the glycosylphosphatidyl (GPI) lipid anchor to the carbonyl
      intermediate of the substrate protein at the omega-site. Its ~300-amino acid
      residue lumenal domain is a M28 family metallo-peptide-synthetase with an
      alpha/beta hydrolase fold, including a central 8-strand beta-sheet and a single
      metal (most likely zinc) ion coordinated by 3 conserved polar residues.
      Phosphoethanolamine is used as an adaptor to make the non-peptide GPI lipid
      anchor look chemically similar to the N terminus of a peptide. 

PMID- 24743170
TI  - Using a standardized patient learning activity to teach baccalaureate nursing
      students about dementia care.
AB  - This department profiles an effort by faculty to integrate geriatric content into
      the baccalaureate curriculum, as a standardized patient experience. This content
      was developed for use in the senior-level psychiatric/mental health clinical
      course to increase the awareness and competencies of students in dealing with
      this aging patients with dementia. 

PMID- 24743171
TI  - Stress within the academic workplace.
AB  - Many new nursing leaders assuming deanships, assistant deanships, or interim
      deanships have limited education, experience, or background to prepare them to
      deal with workplace stress. To assist new deans and those aspiring to be deans,
      the authors of this department offer survival tips based on their personal
      experiences and insights. They address common issues such as time management,
      handling workplace bullying, and negotiating deadlines and assignments. The
      authors welcome counterpoint discussions with readers. 

PMID- 24743169
TI  - Remodeling of aorta extracellular matrix as a result of transient high oxygen
      exposure in newborn rats: implication for arterial rigidity and hypertension
      risk.
AB  - Neonatal high-oxygen exposure leads to elevated blood pressure, microvascular
      rarefaction, vascular dysfunction and arterial (aorta) rigidity in adult rats.
      Whether structural changes are present in the matrix of aorta wall is unknown.
      Considering that elastin synthesis peaks in late fetal life in humans, and early
      postnatal life in rodents, we postulated that transient neonatal high-oxygen
      exposure can trigger premature vascular remodelling. Sprague Dawley rat pups were
      exposed from days 3 to 10 after birth to 80% oxygen (vs. room air control) and
      were studied at 4 weeks. Blood pressure and vasomotor response of the aorta to
      angiotensin II and to the acetylcholine analogue carbachol were not different
      between groups. Vascular superoxide anion production was similar between groups.
      There was no difference between groups in aortic cross sectional area, smooth
      muscle cell number or media/lumen ratio. In oxygen-exposed rats, aorta
      elastin/collagen content ratio was significantly decreased, the expression of
      elastinolytic cathepsin S was increased whereas collagenolytic cathepsin K was
      decreased. By immunofluorescence we observed an increase in MMP-2 and TIMP-1
      staining in aortas of oxygen-exposed rats whereas TIMP-2 staining was reduced,
      indicating a shift in the balance towards degradation of the extra-cellular
      matrix and increased deposition of collagen. There was no significant difference
      in MMP-2 activity between groups as determined by gelatin zymography. Overall,
      these findings indicate that transient neonatal high oxygen exposure leads to
      vascular wall alterations (decreased elastin/collagen ratio and a shift in the
      balance towards increased deposition of collagen) which are associated with
      increased rigidity. Importantly, these changes are present prior to the elevation
      of blood pressure and vascular dysfunction in this model, and may therefore be
      contributory. 

PMID- 24743172
TI  - A solution to the shortage of nursing faculty: awareness and understanding of the
      leadership style of the nursing department head.
AB  - The purpose of this research was to determine if there was a relationship between
      the leadership style of the nursing department head and the level of professional
      satisfaction and organizational commitment by nursing faculty members. The survey
      instrument was designed to measure the department heads' leadership style as
      perceived by the nursing faculty and assess the nursing faculty members' level of
      professional satisfaction and organizational commitment. Five schools of nursing
      in 2 Midwestern states, with a total of 52 full-time baccalaureate nursing
      faculty, were the focus of the inquiry. Findings support statistically
      significant relationships between the 3 variables of department head leadership,
      organizational commitment, and professional satisfaction. Implications for
      leadership style exhibited by the nursing department head are discussed. 

PMID- 24743168
TI  - Analysis of the genome and transcriptome of Cryptococcus neoformans var. grubii
      reveals complex RNA expression and microevolution leading to virulence
      attenuation.
AB  - Cryptococcus neoformans is a pathogenic basidiomycetous yeast responsible for
      more than 600,000 deaths each year. It occurs as two serotypes (A and D)
      representing two varieties (i.e. grubii and neoformans, respectively). Here, we
      sequenced the genome and performed an RNA-Seq-based analysis of the C. neoformans
      var. grubii transcriptome structure. We determined the chromosomal locations,
      analyzed the sequence/structural features of the centromeres, and identified
      origins of replication. The genome was annotated based on automated and manual
      curation. More than 40,000 introns populating more than 99% of the expressed
      genes were identified. Although most of these introns are located in the coding
      DNA sequences (CDS), over 2,000 introns in the untranslated regions (UTRs) were
      also identified. Poly(A)-containing reads were employed to locate the
      polyadenylation sites of more than 80% of the genes. Examination of the sequences
      around these sites revealed a new poly(A)-site-associated motif (AUGHAH). In
      addition, 1,197 miscRNAs were identified. These miscRNAs can be spliced and/or
      polyadenylated, but do not appear to have obvious coding capacities. Finally,
      this genome sequence enabled a comparative analysis of strain H99 variants
      obtained after laboratory passage. The spectrum of mutations identified provides
      insights into the genetics underlying the micro-evolution of a laboratory strain,
      and identifies mutations involved in stress responses, mating efficiency, and
      virulence. 

PMID- 24743173
TI  - Establishing a learning repository to facilitate collaboration and communication
      of academic work among nursing faculty.
AB  - There is an increasing need for collaboration and communication among nurse
      educators to advance the quality of nursing education and show excellence in
      curriculum development, content delivery, leadership, and scholarship roles. In
      this article, the establishment of a learning repository, its unique
      functionalities, procurement of faculty, and future advancements are described in
      detail. Our approach is based on evidence-based research, instructional design,
      and emerging technologies to address the gaps and problems faced by nurse
      educators. 

PMID- 24743175
TI  - Understanding backward design to strengthen curricular models.
AB  - Nurse educators have responded to the call for transformation in education.
      Challenges remain in planning curricular implementation to facilitate
      understanding of essential content for student success on licensure examinations
      and in professional practice. The conceptual framework Backward Design (BD) can
      support and guide curriculum decisions. Using BD principles in conjunction with
      educational models can strengthen and improve curricula. This article defines and
      describes the BD process, and identifies reported benefits for nursing education.

PMID- 24743174
TI  - Using problem-based learning to teach health policy at the DNP level.
AB  - Nursing education recognizes the importance of graduate nurses understanding
      their roles as advocates, developers, implementers, and evaluators of health
      policies to impact the delivery of safe, patient-centered care. This article
      describes the use of problem-based learning as one approach to DNP health policy
      education. Students select a health problem and an associated health policy and
      use evidence-based practice, scholarly writing, and health services research to
      analyze the policy for efficiency, effectiveness, and equity. 

PMID- 24743176
TI  - Identifying at risk individuals for drug and alcohol dependence: teaching the
      competency to students in classroom and clinical settings.
AB  - Alcohol use and other drug use affect patient healthcare outcomes. This article
      describes a classroom-to-clinical approach teaching nursing students to utilize
      motivational interviewing techniques to support patient behavior change. Through
      the lens of a universal prevention method, nursing students learned about reward
      circuit activation leading to risky substance use and the difference between
      addiction and at-risk use. Specific assessment tools and motivational
      interviewing techniques were presented in the classroom. Students then applied
      their knowledge in simulation laboratories and clinical rotations. 

PMID- 24743178
TI  - Bundling the death and dying learning experience for prelicensure nursing
      students.
AB  - One of the greatest challenges in nursing education lies in linking classroom
      content to the clinical environment. Simulation is now an established method for
      allowing students to practice the skills and techniques discussed in didactic
      nursing education and to allow this to occur in a safe, controlled environment
      before moving into the real world of clinical practice. Multidimensional learning
      bundles, such as the End-of-Life Nursing Education Consortium curriculum, provide
      an opportunity to link theoretical content with practice, yet time constraints
      may limit implementation of the full curriculum. A compacted learning bundle with
      a didactic component, unfolding case study, and video-recorded family conference
      to prepare students for a simulation on care of the dying patient is being used
      in 1 accelerated bachelor of science in nursing program to address students'
      learning needs. 

PMID- 24743179
TI  - Guidelines for response to student requests for academic considerations: support
      versus enabling.
AB  - Nursing faculty have a vested interest in student success, and the emphasis on
      caring that is inherent in the nursing profession presents opportunities and
      challenges in dealing with the spectrum of requests from students for academic
      considerations or official disability-related accommodations. This article
      presents contemporary examples of requests for academic consideration or
      notification of disability-related accommodation from nursing students in
      academic or clinical endeavors and provides suggestions for best practice. 

PMID- 24743180
TI  - Undergraduate nursing student experiences with faculty bullies.
AB  - Incivility literature has focused primarily on student-to-faculty incivility,
      whereas less focus has been placed on faculty-to-student bullying. This study
      examined the lived experiences of undergraduate nursing students with faculty
      bullying. Using descriptive phenomenology, this study explored these lived
      experiences. Themes emerged including the emotional experience of bullying, the
      giving and gaining of mutual respect, the value of resilience and persistence,
      and that perception is reality. 

PMID- 24743182
TI  - Using gainsharing to increase electronic end-of-course evaluation submissions.
AB  - The adoption of electronic course evaluations has resulted in a decrease in
      completed evaluations at colleges and universities. Gainsharing is used in
      hospitals to provide an incentive to meet organizational goals. The author
      describes gainsharing and its use to provide a grade incentive for nursing
      students to submit electronic end-of-course evaluations. The effect of the
      incentive on student grades is also examined. 

PMID- 24743183
TI  - New genetic markers for male infertility.
AB  - PURPOSE OF REVIEW: The purpose of this review is to highlight the most important
      advances in the field of genetics of male infertility, with particular attention
      to primary articles dealing with the identification of new genetic and epigenetic
      markers that could be translated into clinical practice in the near future.
      RECENT FINDINGS: Copy number variations (CNVs) of the Y chromosome (gr/gr)
      deletions could already be included in the diagnostic workup of infertile men,
      although confirming studies are needed for CNVs on the X chromosome, as well for
      polymorphisms in some autosomal genes and telomere length in sperm. Methods need
      to be further standardized before sperm DNA analysis could be included in
      clinical practice, although they can help in defining some forms of idiopathic
      infertility. Epigenetic biomarkers are potentially important in elucidating the
      cause of idiopathic male infertility. Polymorphisms in FSHB/FSHR could be used in
      clinical practice to diagnose some forms of male infertility and as a
      pharmacogenetic marker for FSH treatment. SUMMARY: New genetic causes and genetic
      risk factors have been identified in recent years and new technologies for
      genomic and postgenomic analyses (arrays, next-generation sequencing, proteomics,
      metabolomics, global methylome analysis and so on) are promising research fields.
      It is presumed that some of these genetic and epigenetic tests will be introduced
      in clinical practice in the near future.

PMID- 24743184
TI  - Phylogenetic quantification of intra-tumour heterogeneity.
AB  - Intra-tumour genetic heterogeneity is the result of ongoing evolutionary change
      within each cancer. The expansion of genetically distinct sub-clonal populations
      may explain the emergence of drug resistance, and if so, would have prognostic
      and predictive utility. However, methods for objectively quantifying tumour
      heterogeneity have been missing and are particularly difficult to establish in
      cancers where predominant copy number variation prevents accurate phylogenetic
      reconstruction owing to horizontal dependencies caused by long and cascading
      genomic rearrangements. To address these challenges, we present MEDICC, a method
      for phylogenetic reconstruction and heterogeneity quantification based on a
      Minimum Event Distance for Intra-tumour Copy-number Comparisons. Using a
      transducer-based pairwise comparison function, we determine optimal phasing of
      major and minor alleles, as well as evolutionary distances between samples, and
      are able to reconstruct ancestral genomes. Rigorous simulations and an extensive
      clinical study show the power of our method, which outperforms state-of-the-art
      competitors in reconstruction accuracy, and additionally allows unbiased
      numerical quantification of tumour heterogeneity. Accurate quantification and
      evolutionary inference are essential to understand the functional consequences of
      tumour heterogeneity. The MEDICC algorithms are independent of the experimental
      techniques used and are applicable to both next-generation sequencing and array
      CGH data. 

PMID- 24743185
TI  - Communities of endophytic sebacinales associated with roots of herbaceous plants
      in agricultural and grassland ecosystems are dominated by Serendipita herbamans
      sp. nov.
AB  - Endophytic fungi are known to be commonly associated with herbaceous plants,
      however, there are few studies focusing on their occurrence and distribution in
      plant roots from ecosystems with different land uses. To explore the phylogenetic
      diversity and community structure of Sebacinales endophytes from agricultural and
      grassland habitats under different land uses, we analysed the roots of herbaceous
      plants using strain isolation, polymerase chain reaction (PCR), transmission
      electron microscopy (TEM) and co-cultivation experiments. A new sebacinoid strain
      named Serendipita herbamans belonging to Sebacinales group B was isolated from
      the roots of Bistorta vivipara, which is characterized by colourless monilioid
      cells (chlamydospores) that become yellow with age. This species was very common
      and widely distributed in association with a broad spectrum of herbaceous plant
      families in diverse habitats, independent of land use type. Ultrastructurally,
      the presence of S. herbamans was detected in the cortical cells of Plantago
      media, Potentilla anserina and Triticum aestivum. In addition, 13 few frequent
      molecular operational taxonomic units (MOTUs) or species were found across
      agricultural and grassland habitats, which did not exhibit a distinctive
      phylogenetic structure. Laboratory-based assays indicate that S. herbamans has
      the ability to colonize fine roots and stimulate plant growth. Although
      endophytic Sebacinales are widely distributed across agricultural and grassland
      habitats, TEM and nested PCR analyses reinforce the observation that these
      microorganisms are present in low quantity in plant roots, with no evidence of
      host specificity. 

PMID- 24743186
TI  - Involvement of ANXA5 and ILKAP in susceptibility to malignant melanoma.
AB  - Single nucleotide-polymorphisms (SNPs) are a source of diversity among human
      population, which may be responsible for the different individual susceptibility
      to diseases and/or response to drugs, among other phenotypic traits. Several low
      penetrance susceptibility genes associated with malignant melanoma (MM) have been
      described, including genes related to pigmentation, DNA damage repair and
      oxidative stress pathways. In the present work, we conducted a candidate gene
      association study based on proteins and genes whose expression we had detected
      altered in melanoma cell lines as compared to normal melanocytes. The result was
      the selection of 88 loci and 384 SNPs, of which 314 fulfilled our quality
      criteria for a case-control association study. The SNP rs6854854 in ANXA5 was
      statistically significant after conservative Bonferroni correction when 464
      melanoma patients and 400 controls were analyzed in a discovery Phase I. However,
      this finding could not be replicated in the validation phase, perhaps because the
      minor allele frequency of SNP rs6854854 varies depending on the geographical
      region considered. Additionally, a second SNP (rs6431588) located on ILKAP was
      found to be associated with melanoma after considering a combined set of 1,883 MM
      cases and 1,358 disease-free controls. The OR was 1.29 (95% CI 1.12-1.48; p-value
      = 4*10-4). Both SNPs, rs6854854 in ANXA5 and rs6431588 in ILKAP, show population
      structure, which, assuming that the Spanish population is not significantly
      structured, suggests a role of these loci on a specific genetic adaptation to
      different environmental conditions. Furthermore, the biological relevance of
      these genes in MM is supported by in vitro experiments, which show a decrease in
      the transcription levels of ANXA5 and ILKAP in melanoma cells compared to normal
      melanocytes.

PMID- 24743187
TI  - Network-based study reveals potential infection pathways of hepatitis-C leading
      to various diseases.
AB  - Protein-protein interaction network-based study of viral pathogenesis has been
      gaining popularity among computational biologists in recent days. In the present
      study we attempt to investigate the possible pathways of hepatitis-C virus (HCV)
      infection by integrating the HCV-human interaction network, human protein
      interactome and human genetic disease association network. We have proposed quasi
      biclique and quasi-clique mining algorithms to integrate these three networks to
      identify infection gateway host proteins and possible pathways of HCV
      pathogenesis leading to various diseases. Integrated study of three networks,
      namely HCV-human interaction network, human protein interaction network, and
      human proteins-disease association network reveals potential pathways of
      infection by the HCV that lead to various diseases including cancers. The gateway
      proteins have been found to be biologically coherent and have high degrees in
      human interactome compared to the other virus-targeted proteins. The analyses
      done in this study provide possible targets for more effective anti-hepatitis-C
      therapeutic involvement. 

PMID- 24743188
TI  - The effect of temperature on the toxicity of insecticides against Musca domestica
      L.: implications for the effective management of diarrhea.
AB  - BACKGROUND: Diarrhea is an important cause of childhood mortality in developing
      countries like Pakistan because of unhygienic conditions, lack of awareness, and
      unwise use of preventive measures. Mechanical transmission of diarrheal pathogens
      by house flies, Musca domestica, is believed as the most effective route of
      diarrhea transmission. Although the use of insecticides as a preventive measure
      is common worldwide for the management of house flies, success of the measure
      could be compromised by the prevailing environmental temperature since it
      significantly affects toxicity of insecticides and thus their efficacy. Peaks of
      the house fly density and diarrheal cases are usually coincided and season
      specific, yet little is known about the season specific use of insecticides.
      METHODOLOGY/PRINCIPAL FINDINGS: To determine the temperature-toxicity
      relationship in house flies, the effect of post-bioassays temperature (range, 20
      34 degrees C) on the toxicity of seven insecticides from organophosphate
      (chlorpyrifos, profenofos), pyrethroid (cypermethrin, deltamethrin) and new
      chemical (emamectin benzoate, fipronil, spinosad) classes was evaluated by using
      a feeding bioassay method. From 20-34 degrees C, the toxicities of chlorpyrifos,
      profenofos, emamectin and fipronil increased 2.10, 2.93, 2.40 and 3.82 fold (i.e.
      positive temperature coefficient), respectively. Whereas, the toxicities of
      cypermethrin, deltamethrin and spinosad decreased 2.21, 2.42 and 3.16 fold (i.e.
      negative temperature coefficient), respectively. CONCLUSION/SIGNIFICANCE: These
      findings suggest that for the reduction in diarrheal cases, house flies should be
      controlled with insecticides according to the prevailing environmental
      temperature. Insecticides with a positive temperature coefficient may serve as
      potential candidates in controlling house flies and diarrhea epidemics in hot
      season and vice versa.

PMID- 24743190
TI  - [Tumor lysis syndrome and clinical guidelines].
AB  - Tumor lysis syndrome(TLS)is a life-threatening metabolic abnormality caused by
      the massive and abrupt release of tumor cell components into the blood. TLS can
      be classified as laboratory TLS(LTLS)or clinical TLS(CTLS). LTLS is characterized
      by 2 or more of the following metabolic abnormalities: hyperuricemia,
      hyperkalemia, and hyperphosphatemia. CTLS comprises LTLS in addition to 1 or more
      of the following symptoms: renal insufficiency, cardiac arrhythmia/sudden death,
      and seizures. The prevention and treatment of TLS includes rigorous hydration,
      hyperuricemia management, and frequent monitoring of electrocytes and correction
      of electrolyte abnormalities. Rasburicase, a recombinant urate oxidase, can
      rapidly reverse hyperuricemia. With the introduction of rasburicase in clinical
      practice, a clinical practice guideline has been released and a recommended risk
      assessment method and prophylaxis have been advocated. This guideline can be
      applied uniformly to all patients, not only those with hematological
      malignancies, but also those with solid tumors. However, the medical environment
      is changing, with the introduction of a large number of molecular targeted drugs
      in clinical practice. In the rasburicase era, the serum phosphate concentration
      will become the most important risk factor associated with CTLS. This guideline
      will have to be re-evaluated in the near future. 

PMID- 24743189
TI  - Gender perspective of risk factors associated with disclosure of HIV status, a
      cross-sectional study in Soweto, South Africa.
AB  - BACKGROUND: Human Immunodeficiency Virus (HIV) status disclosure has been shown
      to provide several benefits, both at the individual and societal levels. AIM: To
      determine risk factors associated with disclosing HIV status among antiretroviral
      therapy (ART) recipients in South Africa. SETTING: A cross-sectional study on
      risk factors for viremia and drug resistance took place at two outpatient HIV
      clinics in 2008, at a large hospital located in Soweto, South Africa. METHODS: We
      conducted a secondary data analysis on socio-economic characteristics and HIV
      status disclosure to anyone, focusing on gender differences. Descriptive and
      multivariable logistic regression analyses were performed to model the
      associations between risk factors and HIV status disclosure. Additionally,
      descriptive analysis was conducted to describe gender differences of HIV status
      disclosure to partner, parents, parents in law, partner, child, family, employer,
      and other. PATIENTS: A total of 883 patients were interviewed. The majority were
      women (73%) with median age of 39 years. RESULTS: Employed patients were less
      likely to disclose than unemployed (odds ratio (OR) 0.36; 95% confidence interval
      (CI) 0.1-1.0; p = 0.05)). Women with higher income were more likely to disclose
      (OR 3.25; 95% CI 0.90-11.7; p = 0.07) than women with lower income, while men
      with higher income were less likely (OR 0.20; 95% CI 0.02-1.99; p = 0.17) than
      men with lower income. Men were more likely than women to disclose to their
      partner (p<0.01), and to partner and family (p<0.01), women were more likely than
      men to disclose to child and family (p<0.01), to child, family and others (p =
      0.01). CONCLUSION: Being employed imposed a risk factor for HIV status
      disclosure, additionally we found an interaction effect of gender and income on
      disclosure. Interventions designed to reduce workplace discrimination and gender
      sensitive interventions promoting disclosure are strongly recommended.

PMID- 24743191
TI  - [Anti-angiogenic therapy for malignant glioma].
AB  - Glioblastoma(GBM)is the most malignant and frequent primary brain tumor. The
      current standard of care consists of maximum safe resection and radiotherapy with
      concomitant and subsequent temozolomide(TMZ)treatment. With this treatment plan,
      the prognosis of patients with GBM remains dismal, with a 5-year survival rate
      of<10%; thus development of effective, novel therapies is needed.
      Bevacizumab(Bev, Avastin(r))is a humanized monoclonal antibody against vascular
      endothelial growth factor(VEGF), one of the major potent angiogenic factors for
      the growth of human cancers, including GBM. Bev has been shown to effectively
      shrink enhancing lesions of recurrent GBM and decrease symptom burden and brain
      edema. These positive results led to its approval for malignant glioma treatment
      in June 2013 in Japan. Two double-blind, placebo-controlled, randomized phase III
      studies of Bev in newly diagnosed GBM were conducted to verify its efficacy as a
      first-line therapy used in combination with TMZ. The results, which were reported
      at the American Society for Clinical Oncology(ASCO)meeting in June 2013, failed
      to show an increase in overall survival, despite prolongation in progression-free
      survival. These results led to many unsolved issues regarding the use of Bev for
      the treatment of GBM. We discuss these problems in this paper and highlight our
      institutional experience with Bev monotherapy for recurrent high-grade gliomas. 

PMID- 24743192
TI  - [Current progress and management in molecular targeted therapy for advanced
      thyroid cancer].
AB  - Surgery results in improved outcomes for most patients with thyroid cancer, but
      there are no effective treatment options for patients with locally
      advanced/metastatic medullary thyroid cancer(MTC), differentiated thyroid
      cancer(DTC)refractory to radioiodine therapy, or highly malignant anaplastic
      thyroid cancer(ATC). Recent studies have shown that tumorigenesis and
      dedifferentiation of thyroid cancer cells are caused by the activation of several
      major signaling pathways and the related molecular aberrations, as well as by
      angiogenesis mediated by the vascular endothelial growth factor
      receptor(VEGFR)and epidermal growth factor receptor(EGFR). The efficacy of using
      molecular targeted agents for thyroid cancer treatment is under investigation in
      Western countries. In April 2011, the Food and Drug Administration(FDA)approved
      the use of vandetanib for the treatment of advanced MTC based on the results of
      phase III clinical trials. At the 2013 American Society of Clinical
      Oncology(ASCO)meetings, investigators reported that sorafenib improved
      progression-free survival in patients with advanced DTC, according to a phase III
      trial. FDA approved the use of sorafenib for the treatment of advanced DTC in
      November 2013. A multicenter clinical trial for ATC is also currently underway.
      Further research is required in order to characterize the mechanisms of the
      therapeutic response, to delineate the optimal management of drug-related adverse
      effects, and to identify biomarkers that can predict the efficacy of therapy. A
      clinical trial of these novel molecular agents has just begun in Japan, but in
      the near future, this new treatment strategy could become standard treatment for
      patients with advanced thyroid cancer. 

PMID- 24743193
TI  - [Anti-angiogenic therapy in breast cancer].
AB  - Angiogenesis is important for tumor growth and breast cancer development.
      Bevacizumab is a humanized monoclonal antibody that targets vascular endothelial
      growth factor(VEGF)-A, and it is the only anti-angiogenic agent approved for
      breast cancer treatment in Japan. In this article, we discuss the efficacy,
      tolerability, and potential future refinements for the use of bevacizumab. 

PMID- 24743194
TI  - [Gynecologic cancer].
AB  - Angiogenesis is required for cancer growth. To promote vascular sprouting, an
      angiogenic switch is flipped that up-regulates factors such as vascular
      endothelial growth factor(VEGF), fibroblast growth factor(FGF), and
      angiopoietins, and downregulates antiangiogenic factors such as thrombospondin-1
      and angiostatin. Accumulating evidence supports the concept that angiogenesis
      plays a central role in ovarian and cervical carcinogenesis and disease
      progression. Two phase III randomized trials have been published that evaluated
      the addition of bevacizumab to standard chemotherapy as the front-line treatment
      of advanced ovarian cancer. Additional trials have evaluated the combination of
      bevacizumab with chemotherapy in platinum-sensitive and platinum-resistant
      recurrent disease. All these trials showed a statistically significant
      improvement in progression-free survival(PFS), although no improvement in overall
      survival(OS)has been reported. Based on these data, bevacizumab was recently
      approved for the treatment of ovarian cancer in Japan and Europe. Bevacizumab
      plus chemotherapy significantly improves the OS in patients with stage IVB,
      recurrent or persistent cervical carcinoma. The improvement in OS with
      bevacizumab treatment was not accompanied by a decrease in the quality of
      life(QOL). Bevacizumab is the first targeted agent to improve OS in gynecologic
      cancer. 

PMID- 24743195
TI  - [Anti-angiogenic agents of lung cancer].
AB  - Angiogenesis plays an important role in tumor growth; therefore, inhibition of
      angiogenesis is considered a promising treatment strategy. Many signaling
      pathways, such as the vascular endothelial growth factor(VEGF)pathway, the Notch
      pathway, and the integrin pathway, are associated with each other in a complex
      manner; the VEGF signaling pathway plays a central role in angiogenesis.
      Bevacizumab is a humanized monoclonal antibody that specifically targets VEGF-A.
      Two large phase III trials, ECOG4599 and the AVAiL study, showed that bevacizumab
      combined with chemotherapy improves the outcome of patients with nonsquamous non
      small cell lung cancer. Based on these results, bevacizumab is currently the only
      anti-angiogenic agent approved as the first-line of treatment for advanced
      nonsquamous non-small cell lung cancer in Japan. Many anti-angiogenic agents are
      currently in clinical development for the treatment of non-small cell lung
      cancer. These agents show antitumor activity by binding to a ligand and
      inhibiting the activation of receptor tyrosine kinases. However, bevacizumab is
      currently the only agent that extends overall survival. This review mainly
      discusses the results of a recent phase III trial with bevacizumab. We also
      discuss the results of a recent trial with new anti-angiogenic agents. 

PMID- 24743196
TI  - [Renal cell carcinoma].
AB  - Clear cell renal cell carcinoma(ccRCC)with a von Hippel-Lindau(VHL)gene
      alteration is the most frequent histological phenotype of renal cell cancer(RCC).
      This gene alteration suppresses ubiquitination and increases hypoxia-inducible
      factor (HIF)-alpha accumulation, resulting in the upregulation of HIF-alpha
      target genes, which in turn leads to hypervascular tumor formation. Sorafenib,
      sunitinib, axitinib, and pazopanib are kinase inhibitors that block vascular
      endothelial growth factor receptor(VEGFR). Other families of targeted drugs for
      RCC are antibodies against VEGF, such as bevacizumab, and mammalian target of
      rapamycin inhibitors, such as temsirolimus and everolimus, which exert anti
      angiogenic effects by downregulating HIF-alpha expression. Thus, the newly
      developed targeted drugs for RCC are classified as anti-angiogenic drugs.
      However, the frequency of a sustained complete response(CR)in response to these
      drugs is quite low, indicating that the exploration of other modalities of
      treatment, besides anti-angiogenic drugs, is warranted. 

PMID- 24743197
TI  - [Retrospective analysis of clinical and pathological factors that influence
      patient survival in salivary gland cancer - could chemotherapy improve survival
      ?].
AB  - The purpose of this retrospective study was to evaluate the prognostic factors in
      salivary gland cancer using a multivariate analysis. In total, 45 consecutive
      patients who underwent planned radical resection for salivary gland cancer
      between 1985 and 2010 were analyzed. Univariate and multivariate analyses were
      performed to analyze the clinical and pathological factors that influence patient
      survival in salivary gland cancer(tumor location, T and N classification,
      histological grade, excision margin status, postoperative radiotherapy, and
      postoperative adjuvant chemotherapy). The results of the multivariate analysis
      showed that T classification(odds ratio[OR]: 2.93, 95%confidence interval[CI]:
      1.47-5.82), and excision margin status(OR: 4.86, 95% CI: 1.76-13.44)had a
      significant impact on tumor-free survival time, suggesting that both are
      important prognostic factors in salivary gland cancer. Moreover, postoperative
      adjuvant chemotherapy showed a tendency to improve tumor free survival time(OR:
      0.28, 95% CI: 0.07-1.11), thereby indicating its potential in improving prognosis
      in patients with salivary gland cancer.

PMID- 24743198
TI  - [Transarterial infusion chemotherapy using fine-powder cisplatin in patients with
      advanced hepatocellular carcinoma].
AB  - We investigated the therapeutic effects and safety of fine powder cisplatin for
      patients with advanced hepatocellular carcinoma( HCC). From January 2006 to March
      2012, 123 patients with advanced HCC were treated by transarterial infusion
      chemotherapy(TAI)with fine-powder cisplatin(IA-call(r), Nippon Kayaku Co. Ltd.,
      Tokyo, Japan). The drug was infused into the liver through the feeding artery at
      a dose of 65 mg/m2. The treatment was repeated every 4 to 8 weeks until evidence
      of either tumor progression or unacceptable toxicity appeared. Treatment
      responses were classified as complete response(CR), partial response(PR), stable
      disease(SD), and progressive disease(PD)in 3.2%, 12.0%, 32.2%, and 52.4% of
      patients, respectively. The median survival durations were as follows: overall,
      12.2 months; CR/PR patients, 23.8 months; and SD/PD patients, 10.6 months. The
      cumulative survival rates of CR/PR patients were significantly higher than those
      of SD/PD patients (p<0.05). Multivariate analyses revealed that treatment
      response, etiology, Child-Pugh grading, and level of protein induced by the
      vitamin K antagonist- II (PIVKA- II )were predictive factors of survival
      duration. Problematic adverse events were not observed in any of the patients.
      Our results suggest that TAI using fine-powder cisplatin can be safely
      administered for advanced HCC and can improve the prognosis of patients with
      advanced disease.

PMID- 24743199
TI  - [Effect of oral dexamethasone given 24 hours previously on docetaxel-induced
      edema: a retrospective study].
AB  - In Europe and the United States, beginning steroid treatment on the day before
      docetaxel(DTX)administration is recommended to reduce edema and/or
      hypersensitivity symptoms. In this study, we investigated the usefulness of
      starting steroid treatment on the day before DTX administration. Patients with
      breast cancer who received 4 or more cycles of DTX with or without trastuzumab or
      DTX and cyclophosphamide(TC)with or without trastuzumab as pre- or post-operative
      chemotherapy in our hospital between January 2010 and May 2012 were analyzed in
      this retrospective study. Patients were classified as those who started taking
      steroids on the day of DTX administration(GroupA: 62 patients)and those who
      started taking steroids on the day before DTX administration(GroupB: 47
      patients). The incidence of edema and/or hypersensitivity was retrospectively
      compared between these groups after the completion of 4 cycles of chemotherapy.
      The incidence of edema was significantly lower in GroupB (n=12, 25.5%)than in
      GroupA (n=28, 45.2%; p=0.04). The onset of edema also tended to be later in
      GroupB. The incidence of hypersensitivity tended to be lower in GroupB(n=3,
      6.4%)than in GroupA (n=8, 12.9%), although this difference was not statistically
      significant. These results suggest the benefit of steroid treatment started on
      the day before DTX administration in preventing the development of edema. Results
      also suggest that the onset of edema could be delayed by this administration
      method. We recommend that steroid premedication, which can lead to a reduction in
      adverse drug reactions to DTX, be used to help maintain patients' quality of
      life(QOL)and to support treatment continuation.

PMID- 24743200
TI  - [Efficacy and safety of eribulin for metastatic breast cancer patients].
AB  - In the EMBRACE trial, eribulin was reported to significantly increase overall
      survival compared to treatment of the physician 's choice when given to patients
      with recurrent or metastatic breast cancer who had received prior treatment,
      including an anthracycline and a taxane. In April 2011, eribulin was approved in
      Japan for the treatment of inoperable or recurrent breast cancer. In this
      article, we report on the efficacy and safety of eribulin in cases we
      encountered. Twenty patients with advanced and recurrent breast cancer were
      administered eribulin in our hospital during the period from August 2011 to
      December 2012. The median age was 62 years(range, 42-76 years); 16 patients had
      the estrogen receptor(ER)(+)/human epidermal growth factor receptor 2(HER2)(
      )subtype, whereas 4 patients had the triple-negative subtype. Following
      recurrence, the median number of chemotherapy regimens was 3(range, 0-5).
      Regarding the antitumor effects of eribulin, no cases showed complete
      response(CR), 5 cases showed partial response(PR), and 10 cases showed stable
      disease(SD); therefore, the response rate(CR+PR)was 25% and the clinical benefit
      rate(CR+PR+B6-month SD)was 35%. Median progression free survival was 146 days,
      and median overall survival was 482 days. In terms of adverse events(AEs),
      observed cases of hematotoxicity were of neutropenia(75%), leucopenia(75%), and
      anemia(80%). Cases of Grade 3 hematotoxicity or higher were of neutropenia(40%),
      leucopenia(20%), and febrile neutropenia(1 case, 5%). The observed non
      hematotoxic AEs were peripheral neuropathy(30%)and general malaise(35%), although
      none were of Grade 3 or higher. The therapeutic efficacy of eribulin in the
      present study was relatively better than that in previous reports(EMBRACE trial,
      Japan Domestic 221 trial). The frequency of Grade 3 or higher AEs was low, and
      the drug was well tolerated. We believe that eribulin is a novel drug that
      provides therapeutic efficacy while maintaining quality of life(QOL).

PMID- 24743201
TI  - [Effectiveness of skin icing for reducing pain associated with luteinizing
      hormone-releasing hormone agonist injection].
AB  - We evaluated the effect of using the cooling method on pain at the site of
      luteinizing hormone-releasing hormone(LH-RH) agonist injection in 181 prostate
      cancer or premenopausal breast cancer patients by using a numerical rating
      scale(NRS)and a questionnaire survey with open-ended questions. According to the
      NRS, 38.1% of the patients experienced a reduction in pain, 37.5% experienced no
      change, and 24.4% experienced an increase in pain. Therefore, use of the cooling
      method did not have a statistically significant effect in terms of pain
      reduction(p=0.123). However, on analyzing pain reduction according to the answers
      in the questionnaire survey, 53.2% of the patients experienced a reduction in
      pain, 38.5% experienced no change, and 8.3% experienced an increase in pain.
      These findings were different from those obtained on using the NRS. In addition,
      irrespective of using the cooling method, needle thickness and patient obesity
      strongly influenced the pain experienced. The skin icing method was effective in
      reducing pain at the site of LH-RH agonist injection. This method is simple,
      inexpensive, and safe, and is hence recommended. 

PMID- 24743202
TI  - [A case of bisphosphonate-related osteonecrosis of the jaw in a patient who had
      received intravenous bisphosphonates].
AB  - Bisphosphonates(BPs)have been widely used for the treatment of hypercalcemia
      associated with cancer, multiple myeloma bone diseases, and bone metastasis of
      solid cancers. Many cases of bisphosphonate-related osteonecrosis of the jaw
      (BRONJ)have been reported in Japan. We report a case of a patient who developed
      BRONJ after tooth extraction even though the administration of BPs had been
      discontinued for 23 months. The patient was a 74-year-old woman who had received
      intravenous BPs from 2003 through 2008. She underwent tooth extraction in 2010.
      The bone in the extraction socket was exposed for more than 8 weeks. A clinical
      diagnosis of BRONJ was made. Discontinuation of BPs before surgical dental
      treatment did not appear to prevent BRONJ in this patient who had received
      intravenous BPs. 

PMID- 24743205
TI  - [A case of bone metastases from hepatocellular carcinoma presenting with
      erythrocytosis after hepatectomy].
AB  - A 57-year-old man was admitted for careful examination of lower limb edema.
      Abdominal computed tomography(CT) showed hepatocellular carcinoma(HCC), 2 cm in
      diameter, arising in liver segment S6. Posterior segmentectomy was performed, and
      histological examination of the specimen revealed poorly differentiated HCC. Nine
      months after surgery, a metastatic tumor was detected in the left scapula, and
      the patient gradually began to show a high blood concentration of hemoglobin and
      erythropoietin(Epo). Sorafenib was started but was discontinued because of
      intractable diarrhea. The patient died of the metastatictumor 15 months after
      surgery. This is the first case report of a patient with metastaticHCC developing
      erythrocytosis associated with a high concentration of Epo. 

PMID- 24743204
TI  - [Pneumothorax after treatment with bevacizumab-containing chemotherapy for breast
      cancer - a case report].
AB  - A 62-year-old woman presented with a right breast tumor. Examination yielded a
      diagnosis of right breast cancer (T4bN3bM1[lung]). After right breast mastectomy
      for local control, 9 sessions of chemotherapy containing an anthracycline and
      taxane were administered. Because of progression of lung metastasis, bevacizumab
      and paclitaxel were administered. Follow-up computed tomography(CT)scans showed
      that the multiple solid lung metastases had reduced in size, but a hollowing
      effect was noted. Eight months later, the patient developed left pneumothorax.
      The origin of the pneumothorax was unclear, but the hollowing due to the lung
      metastases seen after bevacizumab treatment was thought to be the cause. The
      pneumothorax resolved after tube thoracostomy, but disease progression occurred
      because of the lack of chemotherapy, and the patient's general condition
      worsened. Although rare, we speculate that there is a risk of pneumothorax after
      bevacizumab- containing chemotherapy. 

PMID- 24743207
TI  - [A case of complete response(CR)to S-1 and paclitaxel(PTX)combination therapy in
      a patient with unresectable gastric cancer].
AB  - We report a case of a patient with unresectable gastric cancer who showed
      complete response(CR)to S-1 and paclitaxel (PTX)combination therapy. The
      patient(a 67-year-old woman)was diagnosed with unresectable advanced gastric
      cancer with metastases in the Virchow's lymph nodes and para-aortic lymph nodes.
      Systemic chemotherapy with 70mg/m2 S-1 (days 1-14)and 70mg/m2 PTX(day 1)was
      administered every 3 weeks. At the end of 7 courses of chemotherapy, the primary
      lesion and swollen lymph nodes became markedly smaller. After 7 courses, an
      additional 39 courses were administered over 2.5 years. No notable adverse events
      were seen, and the patient's performance status(PS)was 0. CR was monitored by
      imaging studies. No cancer cells were detected on cytological examination of the
      primary lesion. Monotherapy with 70mg/m2 S-1(days 1-28, 2-week drug holiday)has
      been administered for the past 3 years. The patient is currently treated as an
      outpatient and maintains CR and a PS of 0. 

PMID- 24743208
TI  - [Gastrectomy for a patient with advanced gastric cancer with spleen metastases
      following induction chemotherapy with S-1 plus cisplatin].
AB  - An asymptomatic 56-year-old woman, upon medical examination, was diagnosed with
      advanced adenocarcinoma of the upper third of the stomach. Computed tomography
      showed that the primary gastric tumor was directly invading the splenic hilum,
      and there were multiple metastases in the spleen; incurable gastric cancer was
      confirmed. S-1 plus cisplatin therapy was introduced as the induction regimen,
      and the main tumor and splenic metastases reduced significantly. Total
      gastrectomy with splenectomy and D2 lymphadenectomy was performed after 9 courses
      of chemotherapy. The surgery was completed with no residual tumor, and
      intraperitoneal washing cytology was negative. Histologically, the primary tumor
      was classified as Grade 2, reflecting the effect of chemotherapy, and viable
      metastatic tumors were confirmed in the spleen. S-1-based treatment was continued
      as adjuvant chemotherapy, and the patient was alive with no evidence of tumor
      recurrence 39 months after the initiation of chemotherapy. Although metastasis to
      the spleen from gastric adenocarcinoma has been reported as a rare metastatic
      pattern with poor prognosis, our patient had a long survival time after
      gastrectomy following induction chemotherapy. 

PMID- 24743203
TI  - [A case of a metastatic spine tumor treated using a multidisciplinary approach].
AB  - A 5 0-year-old man who was a hepatitis B carrier was admitted with back pain due
      to bone metastasis of the 12 th thoracic vertebra(Th12)in November 2011. He had
      been diagnosed with liver cancer in January 2010 and underwent liver resection
      following hepatic arterial chemoembolization. He presented with performance
      status(PS)2 and a numeric rating scale(NRS) pain score of 8 out of 10 at the time
      of admission. We started the patient on radiation and drug therapy, but lower
      limb muscle weakness(manual muscle test[MMT]grade 4 out of 5, Frankel D
      classification)occurred on day 12 after admission. Therefore, we immediately
      consulted the orthopedician, and the patient underwent posterior decompression
      fixation on day 15, followed by radiation therapy and rehabilitation. Even after
      discontinuation of all analgesics, his pain level on the NRS was 0, and he had no
      progressive muscle weakness. We ensured long-term care as well as nursing home
      visits. The patient was discharged on day 61. We have a variety of criteria for
      the selection of surgery for spinal metastasis, including Tokuhashi, Tomita, and
      Katagiri scores. The patient's general condition and prognosis are important
      factors to consider when selecting surgical therapy. In the present case, because
      of selection of the appropriate treatment and timely cooperation with
      specialists, it was possible to effectively relieve symptoms and discharge the
      patient to home care. 

PMID- 24743206
TI  - [A case of unresected gastric cancer that maintained long tumor dormancy by use
      of paclitaxel+S-1 combination therapy].
AB  - Here we report a case of unresected gastric cancer that maintained long tumor
      dormancy by use of paclitaxel+S-1 combination therapy. A 58-year-old woman was
      admitted to the hospital for peritoneal dissemination of unresectable gastric
      cancer. The patient further showed ileus with peritoneal dissemination in
      computed tomography(CT), and we performed resection of the intestine to release
      the stenosis. In addition, combination chemotherapy using paclitaxel(60mg/m2,
      weekly) and S-1(80mg/m2, every 2 weeks)was started after the operation. The
      patient was discharged from the hospital 7 3 days after the operation, and we
      continued combination chemotherapy as an outpatient over the following 3 years
      without serious side effects. Furthermore, tumor makers for gastric cancer were
      stable, although we could not examine tumor size since the patient rejected
      examinations such as CT. After 3 years, the patient was admitted to the hospital
      with cholecystitis, and we were able to evaluate the benefit of the chemotherapy
      against gastric cancer. The tumor size clearly remained unchanged compared to
      previous measurements, suggesting that the tumor maintained dormancy in this
      case.

PMID- 24743210
TI  - [A case of gastric cancer accompanied by disseminated carcinomatosis of bone
      marrow wherein long-term chemotherapy was enabled by early supportive palliative
      care].
AB  - Here we report gastric cancer accompanied by bone marrow carcinomatosis in a
      patient for whom long-term chemotherapy was enabled by early pain-relief therapy.
      A 45-year-old man was admitted to our hospital because of back pain associated
      with multiple spinal tumors in June 2011. Blood tests showed a trend toward
      disseminated intravascular coagulation(DIC) and gastric cancer was suspected as
      the primary lesion. Because pain was severe, emergency pain relief was provided
      by flurbiprofen axetil and a continuous subcutaneous infusion of fentanyl
      citrate. After bone marrow examination gave a diagnosis of poorly differentiated
      adenocarcinoma, we performed sequential methotrexate(MTX)and 5-fluorouracil(5
      FU)therapy. The therapy successfully decreased tumor marker levels, and alkaline
      phosphatase and lactate dehydrogenase levels normalized. Finally, gastric cancer
      accompanied by bone marrow carcinomatosis was diagnosed. Because the patient had
      anxiety and spiritual pain from the time of admission, psychiatric care was also
      required. In November 2011, the tumor recurred, and we switched therapy to a
      combination of S-1 and cisplatin. The patient's pain was controlled by combined
      treatment with a fentanyl patch and etodolac, and he was discharged in December
      2011. However, severe pain recurred and pain therapy was continued. DIC developed
      in February 2012 and transiently resolved after resuming combination therapy with
      MTX and 5-FU; however, it subsequently recurred, leading to the patient's death
      in May 2012. 

PMID- 24743209
TI  - [A case of advanced gastric cancer treated with curative resection after
      preoperative combined chemotherapy with docetaxel, cisplatin, and S-1].
AB  - A 67-year-old woman with epigastralgia was admitted to our hospital and was
      diagnosed with type 3 advanced gastric cancer with lymph node metastases.The
      clinical diagnosis was Stage III A(cT3, N2, M0).Since curative surgery was not
      feasible, we administered preoperative combination chemotherapy with docetaxel,
      cisplatin(CDDP), and S-1.After 3 courses of chemotherapy, the lymph nodes became
      undetectable on computed tomography(CT).Distal gastrectomy was performed with
      curative intent, and the final diagnosis was Stage IIA(ypT3, N0, M0).There has
      been no recurrence for 1 year and 4 months after the operation. 

PMID- 24743212
TI  - [Sudden blast crisis of chronic myeloid leukemia after a 13-year durable
      remission following allogeneic bone marrow transplantation and donor lymphocyte
      infusion].
AB  - We describe a rare case of sudden blast crisis of chronic myeloid leukemia that
      occurred after a 13-year durable remission, following allogeneic bone marrow
      transplantation and donor lymphocyte infusion. A 55-year-old Japanese man was
      diagnosed with chronic-phase chronic myeloid leukemia 24 years previously. He
      underwent allogeneic bone marrow transplantation 2 years after diagnosis.
      Although the disease recurred 6 years after transplantation, the patient achieved
      remission again by a donor lymphocyte infusion. Despite a 13-year durable
      remission, the disease later relapsed into a sudden blast crisis. Prednisolone
      and vincristine combined with imatinib mesylate effectively achieved a major
      molecular response. However, the disease relapsed repeatedly with central nervous
      system infiltration. Dasatinib and intrathecal methotrexate, cytarabine, and
      dexamethasone administration via the Ommaya reservoir controlled disease
      progression. Nevertheless, the disease became refractory to treatment with the
      emergence of a T315I Bcr-Abl gene mutation. The patient eventually died 43 months
      post crisis.

PMID- 24743211
TI  - [A case of para-aortic lymph node metastasis from colon cancer with complete
      response to uracil/tegafur plus leucovorin therapy].
AB  - In October 2008, a 66-year-old male patient underwent resection of the right half
      of the colon for ascending colon cancer. Histopathological examination revealed a
      tumor classification of tub2, pSE, ly1, v0, PM0, DM0, RM0, pN1(2/23), H0 , P0 ,
      Stage III a. The patient was treated with uracil/tegafur plus
      Leucovorin(UFT/LV)chemotherapy after surgery. However, he developed Grade 2 liver
      dysfunction after completion of 1 course, so UFT/LV was discontinued. In June
      2009, a rise in the carcinoembryonic antigen(CEA)level was observed, and computed
      tomography(CT)and positron emission tomography with 2-[fluorine-18]fluoro-2-deoxy
      D-glucose(FDG-PET)showed a single enlarged lymph node, 2 cm in diameter, located
      around the aorta. We informed the patient of the therapeutic effect of anticancer
      drug treatment and surgery, risk of adverse events, and other management methods,
      and UFT/LV chemotherapy was selected as treatment. After 3 courses, the lymph
      node had completely disappeared, and UFT/LV was discontinued in April 2011, as
      there was no sign of recurrence. The patient remains alive and well. We report a
      case of para-aortic lymph node metastasis after surgery, treated with UFT/LV,
      which led to a complete response without major adverse events. 

PMID- 24743213
TI  - A highly curable lymphoma occurs preferentially in the proximal tibia of young
      patients.
AB  - The presentation of two 19-year-old male subjects with stage I non-Hodgkin
      lymphoma in the proximal tibia prompted an extensive review of institutional and
      national databases to assess whether there is any statistical evidence that these
      reflected a previously overlooked syndromic pattern of presentation. The
      institutional records of a single institution were reviewed for presentation of
      non-Hodgkin lymphoma in the bone. The records of two additional institutions were
      reviewed for all reports of non-Hodgkin lymphoma in the tibia. Analysis was
      performed on data from Surveillance, Epidemiology, and End Results (SEER)
      dichotomized to bone presentation in the lower extremity versus other bones.
      Institutional databases included 20 patients with tibial presentation of lymphoma
      with a median age of 22.5 years (versus 42 for all bone lymphomas; P<0.001).
      Eighteen out of twenty patients had diffuse large B-cell lymphoma, and all
      patients aged <=40 achieved remission and apparent cure. Distinctive and unusual
      features were a tendency for bilateral involvement of the tibia and sclerotic
      changes on X-ray. SEER data included 808 cases of bone lymphoma; the fraction of
      cases presenting in the lower extremity versus other bone sites is higher at ages
      <=40 years (38% versus 19%; P<0.0001). Presentation in the lower extremity, as
      compared with other bone sites, confers 97% overall survival in patients aged
      <=40 (versus 82%; P=0.01). This survival effect was independent of stage. In
      contrast, no significant difference in overall survival was identified for lower
      extremity versus non-lower extremity site for age >40. These data show a
      previously undescribed syndromic pattern of disease presentation: bone lymphoma
      in young patients is likely to present in the lower extremity-specifically the
      proximal tibia-has atypical sclerotic features on X-ray, is often bilateral, and
      has an excellent prognosis compared with bone lymphomas at other sites matched
      for stage and age. 

PMID- 24743214
TI  - Re-evaluating the role of sentinel lymph node biopsy in microinvasive breast
      carcinoma.
AB  - The role of sentinel lymph node biopsy in microinvasive breast carcinoma is
      unclear. We examined the incidence of lymph node metastasis in patients with
      microinvasive carcinoma who underwent surgery at our institution. Retrospective
      review of our pathology database was performed (1994-2012). Of 7000 patients
      surgically treated for invasive breast carcinoma, 99 (1%) were classified as
      microinvasive carcinoma. Axillary staging was performed in 81 patients (64,
      sentinel lymph node biopsy; 17, axillary lymph node excision). Seven cases (9%)
      showed isolated tumor/epithelial cells in sentinel nodes. Three of these seven
      cases showed reactive changes in lymph nodes, papillary lesions in the breast
      with or without displaced epithelial cells within biopsy site tract, or
      immunohistochemical (estrogen receptor, progesterone receptor, and HER2)
      discordance between the primary tumor in the breast and epithelial cells in the
      lymph node, consistent with iatrogenically transported epithelial cells rather
      than true metastasis. The remaining four cases included two cases, each with a
      single cytokeratin-positive cell in the subcapsular sinus detected by
      immunohistochemistry only, and two cases with isolated tumor cells singly and in
      small clusters (<20 cells per cross-section) by hematoxylin and eosin and
      immunohistochemistry. The exact nature of cytokeratin-positive cells in the
      former two cases could not be determined and might still have represented
      iatrogenically displaced cells. In the final analysis, only two cases (3%) had
      isolated tumor cells. Three of these four cases had additional axillary lymph
      nodes excised, which were all negative for tumor cells. At a median follow-up of
      37 months (range 6-199 months), none of these patients had axillary recurrences.
      Our results show very low incidence of sentinel lymph node involvement (3%), only
      as isolated tumor cells, in microinvasive carcinoma patients. None of our cases
      showed micrometastases or macrometastasis. We recommend reassessment of the
      routine practice of sentinel lymph node biopsy in patients with microinvasive
      carcinoma. 

PMID- 24743215
TI  - Familial colorectal cancer type X: genetic profiles and phenotypic features.
AB  - Heredity is a major cause of colorectal cancer, but although several rare high
      risk syndromes have been linked to disease-predisposing mutations, the genetic
      mechanisms are undetermined in the majority of families suspected of hereditary
      cancer. We review the clinical presentation, histopathologic features, and the
      genetic and epigenetic profiles of the familial colorectal cancer type X (FCCTX)
      syndrome with the aim to delineate tumor characteristics that may contribute to
      refined diagnostics and optimized tumor prevention. 

PMID- 24743216
TI  - Hepatocellular carcinoma arising in adenoma: similar immunohistochemical and
      cytogenetic features in adenoma and hepatocellular carcinoma portions of the
      tumor.
AB  - Well-differentiated hepatocellular carcinoma in non-cirrhotic liver can show
      morphological features similar to hepatocellular adenoma. In rare instances,
      hepatocellular carcinoma can arise in the setting of hepatocellular adenoma. This
      study compares the immunohistochemical and cytogenetic features of the
      hepatocellular adenoma-like and hepatocellular carcinoma portions of these
      tumors. Immunohistochemistry for beta-catenin, glutamine synthetase, serum
      amyloid A protein, glypican-3, and heat-shock protein 70 was done in 11 cases of
      hepatocellular carcinoma arising in hepatocellular adenoma in non-cirrhotic
      liver. Tumors with nuclear beta-catenin and/or diffuse glutamine synthetase were
      considered beta-catenin activated. Fluorescence in situ hybridization (FISH) was
      done in nine cases for gains of chromosomes 1, 8 and MYC. There were seven men
      (33-75 years) and four women (29-65 years). Focal atypical morphological features
      were seen in hepatocellular adenoma-like areas in 7 (64%) cases. Hepatocellular
      adenoma-like areas showed features of inflammatory hepatocellular adenoma in 7
      (64%) cases; 4 of these were also serum amyloid A-positive in the hepatocellular
      carcinoma portion. beta-Catenin activation, heat-shock protein 70 positivity, and
      chromosomal gains on FISH were seen in the hepatocellular adenoma portion in 55%,
      40%, and 56% of cases, and 73%, 60%, and 78% of cases in the hepatocellular
      carcinoma portion, respectively. In conclusion, the hepatocellular adenoma-like
      portion of most cases of hepatocellular carcinoma arising in hepatocellular
      adenoma shows features typically seen in hepatocellular carcinoma such as focal
      morphological abnormalities, beta-catenin activation, heat-shock protein 70
      expression, and chromosomal gains. Hepatocellular adenoma-like areas in these
      tumors, especially in men and older women, may represent an extremely well
      differentiated variant of hepatocellular carcinoma, whereas the morphologically
      recognizable hepatocellular carcinoma portion represents a relatively higher
      grade component of the tumor. 

PMID- 24743217
TI  - Post-surgical outcome for epilepsy associated with type I focal cortical
      dysplasia subtypes.
AB  - Focal cortical dysplasias are a well-recognized cause of medically intractable
      seizures. The clinical relevance of certain subgroups of the International League
      Against Epilepsy (ILAE) classification scheme remains to be determined. The aim
      of the present work is to assess the effect of the focal cortical dysplasia type
      Ib and Ic histologic subtypes on surgical outcome with respect to seizure
      frequency. This study also provides an opportunity to compare the predictive
      value of the ILAE and Palmini et al classification schemes with regard to the
      type I focal cortical dysplasias. We retrospectively reviewed 91 focal cortical
      dysplasia patients (55% female; median age: 19 years (interquartile range 8-34);
      median seizure duration: 108 months (interquartile range 36-204)) with chronic
      epilepsy who underwent surgery. We compared the pathological subtypes, evaluating
      the patients' post-surgical outcome with respect to seizure frequency according
      to the Engel's classification and the ILAE outcome classification. Both the ILAE
      classification scheme and Palmini et al classification scheme were utilized to
      classify the histologic subtype. Using chi(2) and Fisher's exact tests, we
      compared the post-surgical outcomes among these groups. Of the 91 patients, there
      were 50 patients with ILAE focal cortical dysplasia type Ib, 41 with ILAE focal
      cortical dysplasia type Ic, 63 with Palmini et al focal cortical dysplasia type
      IA, and 28 with Palmini et al focal cortical dysplasia type IB. After surgery, 44
      patients (48%) were seizure-free. Crude analysis revealed no significant
      difference between patients with subtypes of ILAE focal cortical dysplasia type I
      or Palmini et al focal cortical dysplasia type I concerning postoperative outcome
      according to the Engel and ILAE scoring systems on seizure frequency. Our
      findings revealed no significant difference concerning surgical outcome with
      respect to seizure frequency for the histologic subtypes of ILAE focal cortical
      dysplasia type I (Ib vs Ic) or Palmini et al focal cortical dysplasia type I (IA
      vs IB). In isolation, the histologic subtype of focal cortical dysplasia type I
      does not appear predictive of postoperative outcome. 

PMID- 24743218
TI  - Detection of minimal residual disease in NPM1-mutated acute myeloid leukemia by
      next-generation sequencing.
AB  - Detection of minimal residual disease predicts adverse outcome in patients with
      acute myeloid leukemia. Currently, minimal residual disease may be detected by RQ
      PCR or flow cytometry, both of which have practical and diagnostic limitations.
      Here, we describe a next-generation sequencing assay for minimal residual disease
      detection in NPM1-mutated acute myeloid leukemia, which encompasses ~60% of
      patients with normal karyotype acute myeloid leukemia. Exon 12 of NPM1 was PCR
      amplified using sequencing adaptor-linked primers and deep sequenced to enable
      detection of low-prevalence, acute myeloid leukemia-specific activating
      mutations. We benchmarked our results against flow cytometry, the standard of
      care for acute myeloid leukemia minimal residual disease diagnosis at our
      institution. The performance of both approaches was evaluated using defined
      dilutions of an NPM1 mutation-positive cell line and longitudinal clinical
      samples from acute myeloid leukemia patients. Using defined control material, we
      found this assay sensitive to approximately 0.001% mutant cells, outperforming
      flow cytometry by an order of magnitude. Next-generation sequencing was precise
      and semiquantitative over four orders of magnitude. In 22 longitudinal samples
      from six acute myeloid leukemia patients, next-generation sequencing detected
      minimal residual disease in all samples deemed negative by flow cytometry.
      Further, in one-third of patients, sequencing detected alternate NPM1 mutations
      in addition to the patient's index mutation, consistent with tumor heterogeneity.
      Next-generation sequencing provides information without prior knowledge of NPM1
      mutation subtype or validation of allele-specific probes as required for RQ-PCR
      assays, and without generation and interpretation of complex multidimensional
      flow cytometry data. This approach may complement current technologies to enhance
      patient-specific clinical decision-making. 

PMID- 24743219
TI  - Histopathologic, immunophenotypic and cytogenetic features of pulmonary
      mucoepidermoid carcinoma.
AB  - Pulmonary mucoepidermoid carcinoma is an uncommon but distinctive manifestation
      of mucoepidermoid carcinoma. Pulmonary mucoepidermoid carcinoma occurs in adults
      and children and can cause diagnostic problems, especially in small biopsies. Few
      studies have characterized the histologic and immunophenotypic features of
      pulmonary mucoepidermoid carcinoma. t(11;19)(q21;p13) is considered disease
      defining for mucoepidermoid carcinoma; its significance in pulmonary
      mucoepidermoid carcinoma warrants further study. Forty three pulmonary
      mucoepidermoid carcinomas were re-reviewed and graded according to the Brandwein
      grading system for mucoepidermoid carcinoma. Four cases were excluded because of
      a split opinion between pathology report and re-review. These cases were negative
      for MAML2 rearrangement by FISH. TTF-1, napsin A, p40 and p63 immunostains were
      scored: 0 (negative), 1 (1-25% tumor cells), 2 (26-50%), 3 (51-75%) or 4 (>75%).
      FISH to detect MAML2 rearrangement used a MAML2-11q21 break-apart probe. Thirty
      nine pulmonary mucoepidermoid carcinoma (4 low, 30 intermediate, 5 high grade)
      contained mucous, epidermoid and intermediate cells and lacked keratinization and
      in situ carcinoma of the overlying epithelium. All cases with available gross
      description (n=22) had a central/endo- or peribronchial location. All 25 cases
      tested for immunohistochemistry were positive (scores 1-4) for p63; 23 also
      expressed p40. In six cases, the p63 score was higher than p40. TTF-1 and napsin
      were uniformly negative in all 25 cases. MAML2 rearrangement was identified by
      FISH in each of the 24 cases tested (3 low, 19 intermediate, 2 high grade).
      Clinical history was available in 29 patients (15 men) (median age, 48 years)
      with follow-up in 24 (median, 8.4 years). Five patients died of unrelated causes;
      one developed metastatic pulmonary mucoepidermoid carcinoma. In conclusion,
      features helpful in distinguishing pulmonary mucoepidermoid carcinoma from other
      lung cancers include its central/endo- or peribronchial location together with
      the presence of mucous cells, p63 expression, lack of keratinization and MAML2
      rearrangement. TTF-1 and napsin are typically not expressed. 

PMID- 24743220
TI  - Frequent mono-allelic loss associated with deficient PTEN expression in imatinib
      resistant gastrointestinal stromal tumors.
AB  - Insufficiency of phosphatase and tensin homolog (PTEN) occurs in numerous tumor
      types and has been implicated as a resistance mechanism to receptor tyrosine
      kinase-targeted therapies in human cancer. In this study, we have performed a
      comprehensive molecular and immunohistochemical characterization of PTEN in 58
      imatinib-naive and 54 imatinib-treated gastrointestinal stromal tumors (GISTs).
      The findings were correlated with clinicopathological data. At the genomic level,
      PTEN was affected mainly by mono-allelic loss, which was significantly less
      frequent in imatinib-naive vs imatinib-resistant tumors (9% vs 39%, P<0.001).
      Neither PTEN mutations nor PTEN promoter hyper-methylation were found. By
      immunohistochemistry, PTEN depletion was clearly related to GIST progression. Low
      PTEN protein expression was common (50%) and often paralleled with total
      immunonegativity in imatinib-resistant tumors. The abnormal PTEN protein
      expression correlated with PTEN loss at the genomic level (P=0.001). In addition,
      the effect of small interfering RNA (siRNA) PTEN knockdown on KIT signaling was
      examined in GIST-T1 and GIST430 cell lines, in the absence or presence of a dual
      PI3K/mTOR inhibitor NVP-BEZ235, alone or in combination with imatinib. In both
      cell lines, siRNA silencing of PTEN resulted in the substantial upregulation of
      PI3K-AKT and MAPK pathways. The MAPK hyperactivation was further potentiated by
      NVP-BEZ235 in the imatinib-sensitive GIST-T1 cells; yet, this effect was
      counteracted efficiently by combined treatment. In the imatinib-resistant GIST430
      cells, neither NVP-BEZ235 alone or in combination with imatinib yielded
      sufficient inhibition of hyper-phosphorylated MAPK and downstream intermediate S6
      protein. In conclusion, depleted PTEN expression associated with mono-allelic
      PTEN loss occurs frequently in imatinib-resistant GIST and might serve as a
      biomarker for stratifying patients for optimal treatment. In vitro, the PTEN
      insufficiency leads to hyperactivation of AKT and MAPK pathways in tumor cells.
      Novel therapies targeting multiple components of the integrated KIT receptor
      signaling pathways in imatinib-resistant GIST warrant further studies. 

PMID- 24743221
TI  - Melanoma arising in association with blue nevus: a clinical and pathologic study
      of 24 cases and comprehensive review of the literature.
AB  - Melanomas arising in association with blue nevi or mimicking cellular blue nevi
      comprise a relatively rare and heterogeneous group of melanomas. It remains
      controversial which prognostic indicators predictive of outcome in conventional
      cutaneous melanomas are applicable to this type of melanoma. Here, we describe
      the clinical and histopathologic features of 24 melanomas arising in association
      with blue nevi and correlate these with clinical outcome. The mean patient age
      was 49 years (range: 23-85) with a slight female predominance (15 females:9
      males). The most common anatomic locations included the head and neck region
      (50%), the trunk (21%), and the buttock/sacrococcygeum (17%). Histologically, the
      tumors were typically situated in the mid to deep dermis with variable
      involvement of the subcutis, but uniformly lacked a prominent intraepithelial
      component. The mean tumor thickness (defined as either the standard Breslow
      thickness or, if not available due to the lack of orientation or lack of
      epidermis, the largest tumor dimension) was 20.9 mm (range: 0.6-130 mm). The mean
      mitotic figure count was 6.5/mm(2) (range: 1-30/mm(2)). Perineural invasion was
      common (38%). Follow-up was available for 21 cases (median 2.1 years). The median
      overall survival, recurrence-free survival, time to local recurrence, and time to
      distant recurrence were 5.2, 0.7, 2.6, and 1.6 years, respectively. Logistic
      regression analyses demonstrated a significant association between tumor
      thickness and recurrence-free survival (hazard ratio=1.02 per mm; P=0.04) and
      reduced time to distant metastasis (hazard ratio=1.03 per mm; P=0.02) with a
      similar trend toward reduced time to local recurrence (hazard ratio=1.02 per mm;
      P=0.07). No other parameters (age, anatomic location, mitotic figures,
      lymphovascular or perineural invasion, or type of associated blue nevus) emerged
      as significant. In addition, we provide a comprehensive review of 109 cases of
      melanoma blue nevus type described in the English literature and summarize our
      findings in this context. 

PMID- 24743222
TI  - Molecular characteristics of urothelial neoplasms in children and young adults: a
      subset of tumors from young patients harbors chromosomal abnormalities but not
      FGFR3 or TP53 gene mutations.
AB  - Urothelial neoplasms in children and young adult patients are rare and
      hypothesized to have a lower rate of recurrence and progression than those of
      older adults. Because of their rarity, data regarding molecular abnormalities in
      these tumors are limited. We studied molecular characteristics of urothelial
      neoplasms from patients under age 30 years using UroVysion fluorescence in situ
      hybridization (chromosomes 3, 7, 17, and 9p21) and DNA mutational analysis for
      the FGFR3 and TP53 genes. Seventeen tumors were identified in patients 6-26 years
      of age, including low-grade papillary urothelial carcinoma (n=10), high-grade
      papillary urothelial carcinoma (n=5), urothelial papilloma (n=1), and papillary
      urothelial neoplasm of low malignant potential (n=1). No tumor demonstrated
      mutation of FGFR3 or TP53. Chromosomal abnormalities were detected only in
      patients aged >=19 years: two low-grade urothelial carcinomas had loss of 9p21 as
      a sole chromosomal abnormality and three high-grade urothelial carcinomas had
      other or multiple chromosomal abnormalities. Under age 19 years, no tumor showed
      molecular abnormalities with either method (five low-grade papillary urothelial
      carcinomas and one each of high-grade papillary urothelial carcinoma, papillary
      urothelial neoplasm of low malignant potential, and urothelial papilloma). Our
      results support the idea that mutations of the FGFR3 and TP53 genes are rare or
      absent in urothelial neoplasms of young patients. In contrast, chromosomal
      abnormalities detected by UroVysion fluorescence in situ hybridization are
      sometimes present in patients above 19-20 years of age. This finding supports the
      recently proposed hypothesis that an age of 19-20 years separates distinct
      molecular pathways of urothelial carcinogenesis. 

PMID- 24743223
TI  - Histopathological analysis of the progression pattern of subungual melanoma: late
      tendency of dermal invasion in the nail matrix area.
AB  - Subungual melanoma is a rare subtype of melanoma that usually originates and
      spreads from the nail matrix. Because of its poor prognosis and short matrix-to
      bone distance, amputation has been traditionally performed. Recently,
      conservative surgery has been attempted for early subungual melanoma, but the
      evidence supporting this practice is sparse. As little is known about the
      progression pattern of subungual melanoma, further advances on the subject may
      provide better guidance on the optimal surgical approach. Histopathology slides,
      clinical records, and photographs of 23 cases of subungual melanoma were
      reviewed. For all cases, each area of the nail unit-proximal nail fold, nail
      matrix, nail bed, and/or hyponychium-in longitudinal sections was available for
      histological examination. Growth pattern, dermal invasion, and thickness were
      assessed in each area of the nail unit. There were five cases of melanoma in
      situ. Eighteen cases showed dermal invasion in at least one area of the nail
      unit. There were no cases showing dermal invasion in the nail matrix area only.
      In four cases, dermal invasion involved areas of the nail unit other than the
      nail matrix. In 14 cases, dermal invasion involved the nail matrix area as well
      as other areas of the nail unit. Except for one case, the nail matrix area showed
      thinner dermal invasion compared with dermal invasion in other areas of the nail
      unit. In conclusion, dermal invasion of subungual melanoma in the nail matrix
      area tends to occur later than other areas of the nail unit. Longitudinal
      incisional biopsy is necessary to accurately evaluate melanoma invasion. The
      findings of this study suggest that conservative surgical treatment for early
      subungual melanoma may be justified as the nail matrix area, an area of thin
      dermis and close proximity to the underlying bone, appears to be more resistant
      to invasion. 

PMID- 24743224
TI  - A longitudinal assessment of adherence with immunosuppressive therapy following
      kidney transplantation from the Mycophenolic Acid Observational REnal Transplant
      (MORE) study.
AB  - BACKGROUND: Nonadherence with immunosuppressive therapy after renal
      transplantation is a major clinical concern, but longitudinal data are sparse.
      Adherence data were recorded during the Mycophenolic Acid Observational REnal
      Transplant (MORE) study to help inform compliance management decisions. MATERIAL
      AND METHODS: Prospective data were analyzed from the four-year, observational
      MORE study of de novo adult renal transplant recipients receiving mycophenolic
      acid (MPA) as enteric-coated mycophenolate sodium (EC-MPS) or mycophenolate
      mofetil (MMF) at 40 US sites under routine management. Adherence was assessed
      using the Immunosuppressant Therapy Adherence Scale (ITAS): total score 0-12 (12,
      adherence; <12, nonadherence). A logistic regression model was used to identify
      factors associated with nonadherence. RESULTS: In total, 808/946 recipients
      (85.4%) provided >=1 ITAS score. Nonadherence was reported by 24.8%, 31.5%,
      33.0%, 39.8%, 35.4% and 26.4% at months 3, 6, 12, 24, 36 and 48, respectively.
      Mean ITAS score was higher with EC-MPS vs. MMF at months 24 (11.3[1.0] vs.
      10.9[1.4], p=0.001) and 36 (11.4[1.0] vs. 11.1[11.3], p=0.024). The odds ratio
      for nonadherence was 1.60 (95% CI 1.17, 2.19; p=0.003) for African Americans vs.
      non-African Americans. The rate of biopsy-proven acute rejection was 12.7%
      (51/401) in nonadherent recipients vs. 11.3% (46/406) in adherent recipients
      (p=0.59); graft loss was 4.7% (19/402) vs. 3.0% (12/406) (p=0.20); death was 1.5%
      (6/402) vs. 4.7% (19/406) (p=0.013). CONCLUSIONS: Adherence to the
      immunosuppressive regimen decreases over time, highlighting the need to monitor
      and encourage adherence even in long-term maintenance kidney transplant patients.
      Other than African American race, demographic factors may be of limited value in
      predicting nonadherence.

PMID- 24743225
TI  - Microarray analysis of siberian ginseng cyclic somatic embryogenesis culture
      systems provides insight into molecular mechanisms of embryogenic cell cluster
      generation.
AB  - Four systems of cyclic somatic embryogenesis of Siberian ginseng (Eleutherococcus
      senticosus Maxim) were used to study the mechanism of embryonic cell cluster
      generation. The first, direct somatic embryo induction (DSEI), generates
      secondary embryos directly from the primary somatic embryos; the second, direct
      embryogenic cell cluster induction (DEC)), induces embryogenic cell clusters
      directly from somatic embryos in agar medium. Subsequently, we found that when
      DEC-derived somatic embryos are transferred to suspension culture or a bioreactor
      culture, only somatic embryos are induced, and embryogenic cell clusters cannot
      form. Therefore, these new lines were named DEC cultured by liquid medium (ECS)
      and DEC cultured by bioreactor (ECB), respectively. Transmission electron
      microscopy showed that DEC epidermal cells contained a variety of inclusions,
      distinct from other lines. A cDNA library of DEC was constructed, and 1,948 gene
      clusters were obtained and used as probes. RNA was prepared from somatic embryos
      from each of the four lines and hybridized to a microarray. In DEC, 7 genes were
      specifically upregulated compared with the other three lines, and 4 genes were
      downregulated. EsXTH1 and EsPLT1, which were among the genes upregulated in DEC,
      were cloned using the rapid amplification of cDNA ends (RACE). Real-time
      quantitative PCR showed EsXTH1 was more highly expressed in DEC than in other
      lines throughout the culture cycle, and EsPLT1 expression in DEC increased as
      culture duration increased, but remained at a low expression level in other
      lines. These results suggest that EsXTH1 and EsPLT1 may be the essential genes
      that play important roles during the induction of embryogenic cell clusters. 

PMID- 24743226
TI  - Impact of aphasia on consciousness assessment: a cross-sectional study.
AB  - BACKGROUND: Previous findings suggest that language disorders may occur in
      severely brain-injured patients and could interfere with behavioral assessments
      of consciousness. However, no study investigated to what extent language
      impairment could affect patients' behavioral responses. Objective. To estimate
      the impact of receptive and/or productive language impairments on consciousness
      assessment. METHODS: Twenty-four acute and subacute stroke patients with
      different types of aphasia (global, n = 11; Broca, n = 4; Wernicke, n = 3;
      anomic, n = 4; mixed, n = 2) were recruited in neurology and neurosurgery units
      as well as in rehabilitation centers. The Coma Recovery Scale-Revised (CRS-R) was
      administered. RESULTS: We observed that 25% (6 out of 24) of stroke patients with
      a diagnosis of aphasia and 54% (6 out of 11) of patients with a diagnosis of
      global aphasia did not reach the maximal CRS-R total score of 23. An
      underestimation of the consciousness level was observed in 3 patients with global
      aphasia who could have been misdiagnosed as being in a minimally conscious state,
      even in the absence of any documented period of coma. More precisely, lower
      subscores were observed on the communication, motor, oromotor, and arousal
      subscales. CONCLUSION: Consciousness assessment may be complicated by the co
      occurrence of severe language deficits. This stresses the importance of
      developing new tools or identifying items in existing scales, which may allow the
      detection of language impairment in severely brain-injured patients.

PMID- 24743227
TI  - Quantifying individual components of the timed up and go using the kinect in
      people living with stroke.
AB  - Background. The Microsoft Kinect presents a simple, inexpensive, and portable
      method of examining the independent components of the Timed Up and Go (TUG)
      without any intrusion on the patient. Objective. This study examined the
      reliability of these measures, and whether they improved prediction of
      performance on common clinical tests. Methods. Thirty individuals with stroke
      completed 4 clinical assessments, including the TUG, 10-m walk test (10MWT), Step
      Test, and Functional Reach test on 2 testing occasions. The TUG was assessed
      using the Kinect to determine 7 different functional components. Test-retest
      reliability was assessed using intraclass correlation coefficient (ICC),
      redundancy using Spearman's correlation, and score prediction on the clinical
      tests using multiple regression. Results. All Kinect-TUG variables possessed
      excellent reliability (ICC(2,k) > 0.90) except trunk flexion angle (ICC = 0.73).
      Trunk flexion angle and first step length were nonredundant with total TUG time.
      When predicting 10MWT and Step Test scores, adding step length into regression
      models comprising age and total TUG time improved model performance by 7% (P
      <.01) and 6% (P =.03), respectively. Specifically, an interquartile range
      increase in first step length (0.19 m) was associated with a 0.15 m/s faster gait
      speed and 1.8 more repetitions on the Step Test. These effect sizes were
      comparable to our minimal detectable change scores of 0.17 m/s for gait speed and
      1.71 repetitions for the Step Test. Conclusions. Using the Kinect to
      independently assess the multiple components of the TUG may provide reliable and
      clinically useful information. This could enable efficient and information-rich
      large-scale assessments of physical deficits following stroke. 

PMID- 24743228
TI  - Community-based exercise for chronic disease management: an Italian design for
      the United States?
AB  - Although only a small proportion of older adults in the United States engage in
      recommended amounts of physical exercise, the health benefits of exercise for
      this population and the potential for lowering health care costs are substantial.
      However, access to regular exercise programs for the frail elderly and
      individuals with disabilities remains limited. In the context of health reform
      and emerging opportunities in developing integrated systems of care, the
      experience in Tuscany in implementing a community-based program of exercise for
      the elderly should be of interest. 

PMID- 24743230
TI  - Comparison between itraconazole and cotrimoxazole in the treatment of
      paracoccidiodomycosis.
AB  - BACKGROUND: There are no published reports on studies comparing itraconazole
      (ITC), sulfamethoxazole-trimethoprim (cotrimoxazole, CMX), and ITC followed by
      CMX (ITC/CMX) in the treatment of paracoccidiodomycosis. This study aimed to
      compare the efficacy, effectiveness, safety and time to clinical and serologic
      cure in paracoccidioidomycosis patients treated with ITC or CMX, the antifungal
      agents most widely used. METHODOLOGY: A quasi-experimental study was performed in
      177 patients with a confirmed or probable diagnosis of paracoccidioidomycosis.
      Treatment was divided into two stages: 1) initial, which was continued until
      clinical cure was achieved and the erythrocyte sedimentation rate decreased to
      normal values; 2) complementary, which was continued until serologic cure was
      achieved. Medians were compared via the Mann-Whitney test, and frequencies were
      compared via the chi-squared test. The assessment of variables as a function of
      time was performed using Kaplan-Meier curves and Cox regression. The significance
      level was established as p<=0.05. PRINCIPAL FINDINGS: No difference was found in
      the efficacy and effectiveness of the initial treatment of 47 individuals given
      ITC and 130 individuals given CMX; however, the time to clinical cure was shorter
      in the former compared with the latter group (105 vs. 159 days; p = 0.001),
      specifically in patients with the chronic form. Efficacy and effectiveness of the
      three regimens were similar in the complementary treatment; however, the time to
      serologic cure was shorter when ITC (161 days) or CMX (495 days) was used
      compared with ITC/CMX (881 days) [p = 0.02]. The independent predictors of a
      shorter time to serologic cure were treatment with ITC [risk ratio = 6.61 (2.01
      21.75)] or with CMX [risk ratio = 5.11 (1.91-13.67)]). The prevalence of side
      effects was lower with ITC (6.4%) than with CMX (20.0%; p = 0.03). CONCLUSIONS:
      Since ITC induced earlier clinical cure and was better tolerated than CMX, such
      triazole should be considered the first-choice for PCM treatment.

PMID- 24743229
TI  - Structural differences explain diverse functions of Plasmodium actins.
AB  - Actins are highly conserved proteins and key players in central processes in all
      eukaryotic cells. The two actins of the malaria parasite are among the most
      divergent eukaryotic actins and also differ from each other more than isoforms in
      any other species. Microfilaments have not been directly observed in Plasmodium
      and are presumed to be short and highly dynamic. We show that actin I cannot
      complement actin II in male gametogenesis, suggesting critical structural
      differences. Cryo-EM reveals that Plasmodium actin I has a unique filament
      structure, whereas actin II filaments resemble canonical F-actin. Both Plasmodium
      actins hydrolyze ATP more efficiently than alpha-actin, and unlike any other
      actin, both parasite actins rapidly form short oligomers induced by ADP. Crystal
      structures of both isoforms pinpoint several structural changes in the monomers
      causing the unique polymerization properties. Inserting the canonical D-loop to
      Plasmodium actin I leads to the formation of long filaments in vitro. In vivo,
      this chimera restores gametogenesis in parasites lacking actin II, suggesting
      that stable filaments are required for exflagellation. Together, these data
      underline the divergence of eukaryotic actins and demonstrate how structural
      differences in the monomers translate into filaments with different properties,
      implying that even eukaryotic actins have faced different evolutionary pressures
      and followed different paths for developing their polymerization properties. 

PMID- 24743231
TI  - The primary cilium: guardian of organ development and homeostasis.
AB  - The primary cilium is an antenna-like organelle that plays a vital role in organ
      generation and maintenance. It protrudes from the cell surface where it receives
      signals from the surrounding environment and relays them into the cell. These
      signals are then integrated to give the required outputs in terms of
      proliferation, differentiation, migration and polarization that ultimately lead
      to organ development and homeostasis. Defects in cilia function underlie a wide
      range of diverse but related human developmental or degenerative diseases.
      Collectively known as ciliopathies, these disorders present with varying severity
      and multiple organ involvement. The appreciation of the medical importance of the
      primary cilium has stimulated a huge effort into studies of the underlying
      cellular mechanisms. These in turn have revealed that ciliopathies result not
      only from defective assembly or organization of the primary cilium, but also from
      impaired ciliary signaling. This special edition of Organogenesis contains a set
      of review articles that highlight the role of the primary cilium in organ
      development and homeostasis, much of which has been learnt from studies of the
      associated human diseases. Here, we provide an introductory overview of our
      current understanding of the structure and function of the cilium, with a focus
      on the signaling pathways that are coordinated by primary cilia to ensure proper
      organ generation and maintenance. 

PMID- 24743232
TI  - A gain of function mutation in TNFRSF11B encoding osteoprotegerin causes
      osteoarthritis with chondrocalcinosis.
AB  - OBJECTIVE: To identify pathogenic mutations that reveal underlying biological
      mechanisms driving osteoarthritis (OA). METHODS: Exome sequencing was applied to
      two distant family members with dominantly inherited early onset primary OA at
      multiple joint sites with chondrocalcinosis (familial generalised osteoarthritis,
      FOA). Confirmation of mutations occurred by genotyping and linkage analyses
      across the extended family. The functional effect of the mutation was
      investigated by means of a cell-based assay. To explore generalisability, mRNA
      expression analysis of the relevant genes in the discovered pathway was explored
      in preserved and osteoarthritic articular cartilage of independent patients
      undergoing joint replacement surgery. RESULTS: We identified a heterozygous,
      probably damaging, read-through mutation (c.1205A=>T; p.Stop402Leu) in TNFRSF11B
      encoding osteoprotegerin that is likely causal to the OA phenotype in the
      extended family. In a bone resorption assay, the mutant form of osteoprotegerin
      showed enhanced capacity to inhibit osteoclastogenesis and bone resorption.
      Expression analyses in preserved and affected articular cartilage of independent
      OA patients showed that upregulation of TNFRSF11B is a general phenomenon in the
      pathophysiological process. CONCLUSIONS: Albeit that the role of the molecular
      pathway of osteoprotegerin has been studied in OA, we are the first to
      demonstrate that enhanced osteoprotegerin function could be a directly underlying
      cause. We advocate that agents counteracting the function of osteoprotegerin
      could comply with new therapeutic interventions of OA.

PMID- 24743233
TI  - Multi-scale effects of nestling diet on breeding performance in a terrestrial top
      predator inferred from stable isotope analysis.
AB  - Inter-individual diet variation within populations is likely to have important
      ecological and evolutionary implications. The diet-fitness relationships at the
      individual level and the emerging population processes are, however, poorly
      understood for most avian predators inhabiting complex terrestrial ecosystems. In
      this study, we use an isotopic approach to assess the trophic ecology of
      nestlings in a long-lived raptor, the Bonelli's eagle Aquila fasciata, and
      investigate whether nestling dietary breath and main prey consumption can affect
      the species' reproductive performance at two spatial scales: territories within
      populations and populations over a large geographic area. At the territory level,
      those breeding pairs whose nestlings consumed similar diets to the overall
      population (i.e. moderate consumption of preferred prey, but complemented by
      alternative prey categories) or those disproportionally consuming preferred prey
      were more likely to fledge two chicks. An increase in the diet diversity,
      however, related negatively with productivity. The age and replacements of
      breeding pair members had also an influence on productivity, with more fledglings
      associated to adult pairs with few replacements, as expected in long-lived
      species. At the population level, mean productivity was higher in those
      population-years with lower dietary breadth and higher diet similarity among
      territories, which was related to an overall higher consumption of preferred
      prey. Thus, we revealed a correspondence in diet-fitness relationships at two
      spatial scales: territories and populations. We suggest that stable isotope
      analyses may be a powerful tool to monitor the diet of terrestrial avian
      predators on large spatio-temporal scales, which could serve to detect potential
      changes in the availability of those prey on which predators depend for breeding.
      We encourage ecologists and evolutionary and conservation biologists concerned
      with the multi-scale fitness consequences of inter-individual variation in
      resource use to employ similar stable isotope-based approaches, which can be
      successfully applied to complex ecosystems such as the Mediterranean.

PMID- 24743234
TI  - Latency correction of event-related potentials between different experimental
      protocols.
AB  - OBJECTIVE: A fundamental issue in EEG event-related potentials (ERPs) studies is
      the amount of data required to have an accurate ERP model. This also impacts the
      time required to train a classifier for a brain-computer interface (BCI). This
      issue is mainly due to the poor signal-to-noise ratio and the large fluctuations
      of the EEG caused by several sources of variability. One of these sources is
      directly related to the experimental protocol or application designed, and may
      affect the amplitude or latency of ERPs. This usually prevents BCI classifiers
      from generalizing among different experimental protocols. In this paper, we
      analyze the effect of the amplitude and the latency variations among different
      experimental protocols based on the same type of ERP. APPROACH: We present a
      method to analyze and compensate for the latency variations in BCI applications.
      The algorithm has been tested on two widely used ERPs (P300 and observation error
      potentials), in three experimental protocols in each case. We report the ERP
      analysis and single-trial classification. MAIN RESULTS: The results obtained show
      that the designed experimental protocols significantly affect the latency of the
      recorded potentials but not the amplitudes. SIGNIFICANCE: These results show how
      the use of latency-corrected data can be used to generalize the BCIs, reducing
      the calibration time when facing a new experimental protocol.

PMID- 24743235
TI  - IL-3 and CSF-1 interact to promote generation of CD11c+ IL-10-producing
      macrophages.
AB  - Unraveling the mechanisms of hematopoiesis regulated by multiple cytokines
      remains a challenge in hematology. IL-3 is an allergic cytokine with the
      multilineage potential, while CSF-1 is produced in the steady state with
      restricted lineage coverage. Here, we uncovered an instructive role of CSF-1 in
      IL-3-mediated hematopoiesis. CSF-1 significantly promoted IL-3-driven CD11c+ cell
      expansion and dampened basophil and mast cell generation from C57BL/6 bone
      marrow. Further studies indicated that the CSF-1/CSF-1R axis contributed
      significantly to IL-3-induced CD11c+ cell generation through enhancing c-Fos
      associated monopoiesis. CD11c+ cells induced by IL-3 or IL-3/CSF-1 were competent
      in cellular maturation and endocytosis. Both IL-3 and IL-3/CSF-1 cells lacked
      classical dendritic cell appearance and resembled macrophages in morphology. Both
      populations produced a high level of IL-10, in addition to IL-1, IL-6 and
      TNFalpha, in response to LPS, and were relatively poor T cell stimulators.
      Collectively, these findings reveal a role for CSF-1 in mediating the IL-3
      hematopoietic pathway through monopoiesis, which regulates expansion of CD11c+
      macrophages. 

PMID- 24743236
TI  - CRISPR/Cas9 allows efficient and complete knock-in of a destabilization domain
      tagged essential protein in a human cell line, allowing rapid knockdown of
      protein function.
AB  - Although modulation of protein levels is an important tool for study of protein
      function, it is difficult or impossible to knockdown or knockout genes that are
      critical for cell growth or viability. For such genes, a conditional knockdown
      approach would be valuable. The FKBP protein-based destabilization domain (DD)
      tagging approach, which confers instability to the tagged protein in the absence
      of the compound Shield-1, has been shown to provide rapid control of protein
      levels determined by Shield-1 concentration. Although a strategy to knock-in DD
      tagged protein at the endogenous loci has been employed in certain parasite
      studies, partly due to the relative ease of knock-in as a result of their mostly
      haploid lifecycles, this strategy has not been demonstrated in diploid or
      hyperploid mammalian cells due to the relative difficulty of achieving complete
      knock-in in all alleles. The recent advent of CRISPR/Cas9 homing endonuclease
      mediated targeted genome cleavage has been shown to allow highly efficient
      homologous recombination at the targeted locus. We therefore assessed the
      feasibility of using CRISPR/Cas9 to achieve complete knock-in to DD-tag the
      essential gene Treacher Collins-Franceschetti syndrome 1 (TCOF1) in human 293T
      cells. Using a double antibiotic selection strategy to select clones with at
      least two knock-in alleles, we obtained numerous complete knock-in clones within
      three weeks of initial transfection. DD-TCOF1 expression in the knock-in cells
      was Shield-1 concentration-dependent, and removal of Shield-1 resulted in
      destabilization of DD-TCOF1 over the course of hours. We further confirmed that
      the tagged TCOF1 retained the nucleolar localization of the wild-type untagged
      protein, and that destabilization of DD-TCOF1 resulted in impaired cell growth,
      as expected for a gene implicated in ribosome biogenesis. CRISPR/Cas9-mediated
      homologous recombination to completely knock-in a DD tag likely represents a
      generalizable and efficient strategy to achieve rapid modulation of protein
      levels in mammalian cells. 

PMID- 24743237
TI  - Foxm1 mediates LIF/Stat3-dependent self-renewal in mouse embryonic stem cells and
      is essential for the generation of induced pluripotent stem cells.
AB  - Activation of signal transducer and activator of transcription 3 (Stat3) by
      leukemia inhibitory factor (LIF) is required for maintaining self-renewal and
      pluripotency of mouse embryonic stem cells (mESCs). Here, we have confirmed
      transcription factor Forkhead Box m1 (Foxm1) as a LIF/Stat3 downstream target
      that mediates LIF/Stat3-dependent mESC self-renewal. The expression of Foxm1
      relies on LIF signaling and is stimulated by Stat3 directly in mESCs. The
      knockdown of Foxm1 results in the loss of mESC pluripotency in the presence of
      LIF, and the overexpression of Foxm1 alone maintains mESC pluripotency in the
      absence of LIF and feeder layers, indicating that Foxm1 is a mediator of
      LIF/Stat3-dependent maintenance of pluripotency in mESCs. Furthermore, the
      inhibition of Foxm1 expression prevents the reprogramming of mouse embryonic
      fibroblasts to induced pluripotent stem cells (iPSCs), suggesting that Foxm1 is
      essential for the reprogramming of somatic cells into iPSCs. Our results reveal
      an essential function of Foxm1 in the LIF/Stat3-mediated mESC self-renewal and
      the generation of iPSCs. 

PMID- 24743238
TI  - Fine mapping of dominant X-linked incompatibility alleles in Drosophila hybrids.
AB  - Sex chromosomes have a large effect on reproductive isolation and play an
      important role in hybrid inviability. In Drosophila hybrids, X-linked genes have
      pronounced deleterious effects on fitness in male hybrids, which have only one X
      chromosome. Several studies have succeeded at locating and identifying recessive
      X-linked alleles involved in hybrid inviability. Nonetheless, the density of
      dominant X-linked alleles involved in interspecific hybrid viability remains
      largely unknown. In this report, we study the effects of a panel of small
      fragments of the D. melanogaster X-chromosome carried on the D. melanogaster Y
      chromosome in three kinds of hybrid males: D. melanogaster/D. santomea, D.
      melanogaster/D. simulans and D. melanogaster/D. mauritiana. D. santomea and D.
      melanogaster diverged over 10 million years ago, while D. simulans (and D.
      mauritiana) diverged from D. melanogaster over 3 million years ago. We find that
      the X-chromosome from D. melanogaster carries dominant alleles that are lethal in
      mel/san, mel/sim, and mel/mau hybrids, and more of these alleles are revealed in
      the most divergent cross. We then compare these effects on hybrid viability with
      two D. melanogaster intraspecific crosses. Unlike the interspecific crosses, we
      found no X-linked alleles that cause lethality in intraspecific crosses. Our
      results reveal the existence of dominant alleles on the X-chromosome of D.
      melanogaster which cause lethality in three different interspecific hybrids.
      These alleles only cause inviability in hybrid males, yet have little effect in
      hybrid females. This suggests that X-linked elements that cause hybrid
      inviability in males might not do so in hybrid females due to differing sex
      chromosome interactions. 

PMID- 24743239
TI  - Prediction and prioritization of rare oncogenic mutations in the cancer Kinome
      using novel features and multiple classifiers.
AB  - Cancer is a genetic disease that develops through a series of somatic mutations,
      a subset of which drive cancer progression. Although cancer genome sequencing
      studies are beginning to reveal the mutational patterns of genes in various
      cancers, identifying the small subset of "causative" mutations from the large
      subset of "non-causative" mutations, which accumulate as a consequence of the
      disease, is a challenge. In this article, we present an effective machine
      learning approach for identifying cancer-associated mutations in human protein
      kinases, a class of signaling proteins known to be frequently mutated in human
      cancers. We evaluate the performance of 11 well known supervised learners and
      show that a multiple-classifier approach, which combines the performances of
      individual learners, significantly improves the classification of known cancer
      associated mutations. We introduce several novel features related specifically to
      structural and functional characteristics of protein kinases and find that the
      level of conservation of the mutated residue at specific evolutionary depths is
      an important predictor of oncogenic effect. We consolidate the novel features and
      the multiple-classifier approach to prioritize and experimentally test a set of
      rare unconfirmed mutations in the epidermal growth factor receptor tyrosine
      kinase (EGFR). Our studies identify T725M and L861R as rare cancer-associated
      mutations inasmuch as these mutations increase EGFR activity in the absence of
      the activating EGF ligand in cell-based assays. 

PMID- 24743240
TI  - Beneficial effect of insulin treatment on islet transplantation outcomes in Akita
      mice.
AB  - Islet transplantation is a promising potential therapy for patients with type 1
      diabetes. The outcome of islet transplantation depends on the transplantation of
      a sufficient amount of beta-cell mass. However, the initial loss of islets after
      transplantation is problematic. We hypothesized the hyperglycemic status of the
      recipient may negatively affect graft survival. Therefore, in the present study,
      we evaluated the effect of insulin treatment on islet transplantation involving a
      suboptimal amount of islets in Akita mice, which is a diabetes model mouse with
      an Insulin 2 gene missense mutation. Fifty islets were transplanted under the
      left kidney capsule of the recipient mouse with or without insulin treatment. For
      insulin treatment, sustained-release insulin implants were implanted
      subcutaneously into recipient mice 2 weeks before transplantation and maintained
      for 4 weeks. Islet transplantation without insulin treatment did not reverse
      hyperglycemia. In contrast, the group that received transplants in combination
      with insulin treatment exhibited improved fasting blood glucose levels until 18
      weeks after transplantation, even after insulin treatment was discontinued. The
      group that underwent islet transplantation in combination with insulin treatment
      had better glucose tolerance than the group that did not undergo insulin
      treatment. Insulin treatment improved graft survival from the acute phase (i.e.,
      1 day after transplantation) to the chronic phase (i.e., 18 weeks after
      transplantation). Islet apoptosis increased with increasing glucose concentration
      in the medium or blood in both the in vitro culture and in vivo transplantation
      experiments. Expression profile analysis of grafts indicated that genes related
      to immune response, chemotaxis, and inflammatory response were specifically
      upregulated when islets were transplanted into mice with hyperglycemia compared
      to those with normoglycemia. Thus, the results demonstrate that insulin treatment
      protects islets from the initial rapid loss that is usually observed after
      transplantation and positively affects the outcome of islet transplantation in
      Akita mice. 

PMID- 24743241
TI  - Contraceptive utilization and associated factors among HIV positive women on
      chronic follow up care in Tigray Region, Northern Ethiopia: a cross sectional
      study.
AB  - BACKGROUND: In sub-Sahara Africa, more than 60% of all new HIV infections are
      occurring in women, infants and young children. Maternal to child transmission is
      responsible for 90% of childhood HIV infection. Preventing unwanted pregnancy
      among HIV positive women is imperative to reduce maternal and infant morbidity
      and mortality. METHODS: A cross-sectional survey was conducted among 964 HIV
      positive women in selected 12 health centers of Tigray region. In this paper,
      analysis was restricted only for 847 women who were sexually active and non
      pregnant. In each health center the number of study participants was allocated
      proportionally to the load of HIV positive women in chronic care clinics. The
      data were entered into EpiData version 3.1, and cleaned and analyzed using Stata
      version 11.1. Descriptive summary of data and logistic regression were used to
      identify possible predictors using odds ratio with 95% confidence interval and P
      value of 0.05. FINDINGS: Three hundred ninety four (46.5%) of all HIV positive
      women had intension to have more children. Three hundred seventy five (44.3%)
      were using contraceptive methods at time of survey. Injectable (70.7%) and male
      condom (47.6%) were most commonly used type of contraceptives. In the
      multivariable analysis, women who were urban dwellers (AOR = 2.55; 95% CI: 1.27,
      5.02), completed primary education (AOR = 2.27; 95% CI: 1.12, 2.86) and those
      openly discussed about contraceptive methods with their husbands or sexual
      partners (AOR = 6.3; 95% CI: 3.42, 11.76) were more likely to use contraceptive.
      Women who have one or more living children were also more likely to use
      contraceptive compared with women with no child. CONCLUSION: Less than half of
      women used contraceptive methods. The use of condoms could impact unintended
      pregnancies and reduced risks of vertical and sexual transmission. Efforts to
      increase contraceptive utilization focusing on the barrier methods should be
      strengthen in HIV/AIDS chronic care units.

PMID- 24743242
TI  - A p38 substrate-specific MK2-EGFP translocation assay for identification and
      validation of new p38 inhibitors in living cells: a comprising alternative for
      acquisition of cellular p38 inhibition data.
AB  - The fundamental role of p38 mitogen-activated protein kinases (MAPKs) in
      inflammation underlines their importance as therapeutic targets for various
      inflammatory medical conditions, including infectious, vascular, neurobiological
      and autoimmune disease. Although decades of research have yielded several p38
      inhibitors, most clinical trials have failed, due to lack of selectivity and
      efficacy in vivo. This underlines the continuous need to screen for novel
      structures and chemotypes of p38 inhibitors. Here we report an optimized MK2-EGFP
      translocation assay in a semi-automated image based High Content Analysis (HCA)
      system to screen a combinatorial library of 3362 proprietary compounds with
      extensive variations of chemotypes. By determining the levels of redistribution
      of MK2-EGFP upon activation of the Rac/p38 pathway in combination with compound
      treatment, new candidates were identified, which modulate p38 activity in living
      cells. Based on integrated analysis of TNFalpha release from human whole blood,
      biochemical kinase activity assays and JNK3 selectivity testing, we show that
      this cell based assay reveals a high overlap and predictability for cellular
      efficacy, selectivity and potency of tested compounds. As a result we disclose a
      new comprehensive short-list of subtype inhibitors which are functional in the
      low nanomolar range and might provide the basis for further lead-optimization. In
      accordance to previous reports, we demonstrate that the MK2-EGFP translocation
      assay is a suitable primary screening approach for p38-MAPK drug development and
      provide an attractive labor- and cost saving alternative to other cell based
      methods including determination of cytokine release from hPBMCs or whole blood. 

PMID- 24743243
TI  - Notch3 pathway alterations in ovarian cancer.
AB  - The Notch pathway plays an important role in the growth of high-grade serous
      ovarian (HGS-OvCa) and other cancers, but its clinical and biologic mechanisms
      are not well understood. Here, we found that the Notch pathway alterations are
      prevalent and significantly related to poor clinical outcome in patients with
      ovarian cancer. Particularly, Notch3 alterations, including amplification and
      upregulation, were highly associated with poor patient survival. Targeting Notch3
      inhibited ovarian cancer growth and induced apoptosis. Importantly, we found that
      dynamin-mediated endocytosis was required for selectively activating Jagged-1
      mediated Notch3 signaling. Cleaved Notch3 expression was the critical determinant
      of response to Notch-targeted therapy. Collectively, these data identify
      previously unknown mechanisms underlying Notch3 signaling and identify new,
      biomarker-driven approaches for therapy.

PMID- 24743245
TI  - Engineering synergy in biotechnology.
AB  - Biotechnology is a central focus in efforts to provide sustainable solutions for
      the provision of fuels, chemicals and materials. On the basis of a recent open
      discussion, we summarize the development of this field, highlighting the distinct
      but complementary approaches provided by metabolic engineering and synthetic
      biology for the creation of efficient cell factories to convert biomass and other
      feedstocks to desired chemicals.

PMID- 24743244
TI  - Disruption of the homogentisate solanesyltransferase gene results in albino and
      dwarf phenotypes and root, trichome and stomata defects in Arabidopsis thaliana.
AB  - Homogentisate solanesyltransferase (HST) plays an important role in plastoquinone
      (PQ) biosynthesis and acts as the electron acceptor in the carotenoids and
      abscisic acid (ABA) biosynthesis pathways. We isolated and identified a T-DNA
      insertion mutant of the HST gene that displayed the albino and dwarf phenotypes.
      PCR analyses and functional complementation also confirmed that the mutant
      phenotypes were caused by disruption of the HST gene. The mutants also had some
      developmental defects, including trichome development and stomata closure
      defects. Chloroplast development was also arrested and chlorophyll (Chl) was
      almost absent. Developmental defects in the chloroplasts were consistent with the
      SDS-PAGE result and the RNAi transgenic phenotype. Exogenous gibberellin (GA)
      could partially rescue the dwarf phenotype and the root development defects and
      exogenous ABA could rescue the stomata closure defects. Further analysis showed
      that ABA and GA levels were both very low in the pds2-1 mutants, which suggested
      that biosynthesis inhibition by GAs and ABA contributed to the pds2-1 mutants'
      phenotypes. An early flowering phenotype was found in pds2-1 mutants, which
      showed that disruption of the HST gene promoted flowering by partially regulating
      plant hormones. RNA-sequencing showed that disruption of the HST gene resulted in
      expression changes to many of the genes involved in flowering time regulation and
      in the biosynthesis of PQ, Chl, GAs, ABA and carotenoids. These results suggest
      that HST is essential for chloroplast development, hormone biosynthesis, pigment
      accumulation and plant development. 

PMID- 24743254
TI  - Metabolism: pathogens love the poison.

PMID- 24743255
TI  - Pluripotency: citrullination unravels stem cells.

PMID- 24743256
TI  - Labeling: palladium brings proteins to life.

PMID- 24743257
TI  - Rethinking biological activation of methane and conversion to liquid fuels.
AB  - If methane, the main component of natural gas, can be efficiently converted to
      liquid fuels, world reserves of methane could satisfy the demand for
      transportation fuels in addition to use in other sectors. However, the direct
      activation of strong C-H bonds in methane and conversion to desired products
      remains a difficult technological challenge. This perspective reveals an
      opportunity to rethink the logic of biological methane activation and conversion
      to liquid fuels. We formulate a vision for a new foundation for methane
      bioconversion and suggest paths to develop technologies for the production of
      liquid transportation fuels from methane at high carbon yield and high energy
      efficiency and with low CO2 emissions. These technologies could support natural
      gas bioconversion facilities with a low capital cost and at small scales, which
      in turn could monetize the use of natural gas resources that are frequently
      flared, vented or emitted.

PMID- 24743258
TI  - A 20-amino-acid deletion in the neuraminidase stalk and a five-amino-acid
      deletion in the NS1 protein both contribute to the pathogenicity of H5N1 avian
      influenza viruses in mallard ducks.
AB  - Since 2003, H5N1-subtype avian influenza viruses (AIVs) with both a deletion of
      20 amino acids in the stalk of the neuraminidase (NA) glycoprotein (A-) and a
      deletion of five amino acids at positions 80 to 84 in the non-structural protein
      NS1 (S-) have become predominant. To understand the influence of these double
      deletions in the NA and NS1 proteins on the pathogenicity of H5N1-subtype AIVs,
      we selected A/mallard/Huadong/S/2005 as a parental strain to generate rescued
      wild-type A-S- and three variants (A-S+ with a five-amino-acid insertion in the
      NS1 protein, A+S- with a 20-amino-acid insertion in the NA stalk, and A+S+ with
      insertions in both NA and NS1 proteins) and evaluated their biological
      characteristics and virulence. The titers of the AIVs with A- and/or S-
      replicated in DEF cells were higher than that of A+S+, and the A-S- virus
      exhibited a replication predominance when co-infected with the other variants in
      DEF cells. In addition, A-S- induced a more significant increase in the
      expression of immune-related genes in peripheral blood mononuclear cells of
      mallard ducks in vitro compared with the other variants. Furthermore, an
      insertion in the NA and/or NS1 proteins of AIVs resulted in a notable decrease in
      virulence in ducks, as determined by intravenous pathogenicity index, and the two
      insertions exerted a synergistic effect on the attenuation of pathogenicity in
      ducks. In addition, compared with A+S+ and A+S-, the A-S+ and A-S- viruses that
      were introduced via the intranasal inoculation route exhibited a faster
      replication ability in the lungs of ducks. These data indicate that both the
      deletions in the NA stalk and the NS1 protein contribute to the high
      pathogenicity of H5N1 AIVs in ducks. 

PMID- 24743259
TI  - Identification of a novel function of CX-4945 as a splicing regulator.
AB  - Alternative splicing is a nearly ubiquitous versatile process that controls gene
      expression and creates numerous protein isoforms with different functions from a
      single gene. The significance of alternative splicing has been confirmed by the
      increasing number of human diseases that are caused by misregulation of splicing
      events. Very few compounds, however, have been reported to act as inhibitors of
      alternative splicing, and their potential clinical use needs to be evaluated.
      Here, we report that CX-4945, a previously well-characterized inhibitor of casein
      kinase 2 (CK2) and a molecule currently in clinical trials (Phase II) for cancer
      treatment, regulates splicing in mammalian cells in a CK2-independent manner.
      Transcriptome-wide analysis using exon array also showed a widespread alteration
      in alternative splicing of numerous genes. We found that CX-4945 potently
      inhibits the Cdc2-like kinases (Clks) in vitro and in turn, leads to suppression
      of the phosphorylation of serine/arginine-rich (SR) proteins in mammalian cells.
      Surprisingly, the overall efficacy of CX-4945 on Clks (IC50 = 3-90 nM) was
      stronger than that of TG-003, the strongest inhibitor reported to date. Of the
      Clks, Clk2 was most strongly inhibited by CX-4945 in an ATP-competitive manner.
      Our research revealed an unexpected activity of the drug candidate CX-4945 as a
      potent splicing modulator and also suggested a potential application for therapy
      of diseases caused by abnormal splicing. 

PMID- 24743261
TI  - Anti-cyclic citrullinated Peptide antibody is associated with interstitial lung
      disease in patients with rheumatoid arthritis.
AB  - OBJECTIVE: Patients with rheumatoid arthritis (RA) are at risk to develop RA
      associated interstitial lung disease (RA-ILD). This retrospective study aimed to
      investigate the potential association of the positivity of serum anti-cyclic
      citrullinated peptide antibody (anti-CCP2) and rheumatoid factor (RF) with RA-ILD
      in RA patients. METHODS: A total of 285 RA patients were recruited at the
      inpatient service of Peking Union Medical College Hospital in China between 2004
      and 2013. Individual patients were evaluated for the evidence of ILD. The
      concentrations of serum anti-CCP2 and RF in individual patients were measured.
      The potential risk factors for ILD in RA patients were assessed by univariate and
      multivariate models. RESULTS: There were 71 RA patients with RA-ILD, accounting
      for 24.9% in this population. The positive rates of anti-CCP2 and RF in the
      patients with RA-ILD were significantly higher than that in the patients with RA
      only (88.7% vs. 67.3%, p<0.001; 84.5% vs. 70.6%, p = 0.02, respectively).
      Univariate and multivariate logistic regression analysis revealed that RA
      patients with positive serum anti-CCP2, but not RF, were associated with an
      increased risk of ILD (crude odds ratio [cOR] 3.83, 95% confidence interval [CI]
      1.74-8.43, p<0.001; adjusted odds ratio [aOR] 3.50, 95% CI 1.52-8.04, p<0.001).
      CONCLUSION: Our findings suggest that positive serum anti-CCP2, but not RF, may
      be associated with RA-ILD in RA patients.

PMID- 24743260
TI  - Effect of fruit juice on glucose control and insulin sensitivity in adults: a
      meta-analysis of 12 randomized controlled trials.
AB  - BACKGROUND: Diabetes mellitus has become a worldwide health problem. Whether
      fruit juice is beneficial in glycemic control is still inconclusive. This study
      aimed to synthesize evidence from randomized controlled trials on fruit juice in
      relationship to glucose control and insulin sensitivity. METHODS: A strategic
      literature search of PubMed, EMBASE, and the Cochrane Library (updated to March,
      2014) was performed to retrieve the randomized controlled trials that evaluated
      the effects of fruit juice on glucose control and insulin sensitivity. Study
      quality was assessed using the Jadad scale. Weighted mean differences were
      calculated for net changes in the levels of fasting glucose, fasting insulin,
      hemoglobin A1c (HbA1c), and homeostatic model assessment of insulin resistance
      (HOMA-IR) using fixed- or random-effects model. Prespecified subgroup and
      sensitivity analyses were performed to explore the potential heterogeneity.
      RESULTS: Twelve trials comprising a total of 412 subjects were included in the
      current meta-analysis. The numbers of these studies that reported the data on
      fasting glucose, fasting insulin, HbA1c and HOMA-IR were 12, 5, 3 and 3,
      respectively. Fruit juice consumption did not show a significant effect on
      fasting glucose and insulin concentrations. The net change was 0.79 mg/dL (95%
      CI: -1.44, 3.02 mg/dL; P = 0.49) for fasting glucose concentrations and -0.74
      uIU/ml (95% CI: -2.62, 1.14 uIU/ml; P = 0.44) for fasting insulin concentrations
      in the fixed-effects model. Subgroup analyses further suggested that the effect
      of fruit juice on fasting glucose concentrations was not influenced by population
      region, baseline glucose concentration, duration, type of fruit juice, glycemic
      index of fruit juice, fruit juice nutrient constitution, total polyphenols dose
      and Jadad score. CONCLUSION: This meta-analysis showed that fruit juice may have
      no overall effect on fasting glucose and insulin concentrations. More RCTs are
      warranted to further clarify the association between fruit juice and glycemic
      control.

PMID- 24743262
TI  - Accounting for pharmacokinetic differences in dual-tracer receptor density
      imaging.
AB  - Dual-tracer molecular imaging is a powerful approach to quantify receptor
      expression in a wide range of tissues by using an untargeted tracer to account
      for any nonspecific uptake of a molecular-targeted tracer. This approach has
      previously required the pharmacokinetics of the receptor-targeted and untargeted
      tracers to be identical, requiring careful selection of an ideal untargeted
      tracer for any given targeted tracer. In this study, methodology capable of
      correcting for tracer differences in arterial input functions, as well as binding
      independent delivery and retention, is derived and evaluated in a mouse U251
      glioma xenograft model using an Affibody tracer targeted to epidermal growth
      factor receptor (EGFR), a cell membrane receptor overexpressed in many cancers.
      Simulations demonstrated that blood, and to a lesser extent vascular
      permeability, pharmacokinetic differences between targeted and untargeted tracers
      could be quantified by deconvolving the uptakes of the two tracers in a region of
      interest devoid of targeted tracer binding, and therefore corrected for, by
      convolving the uptake of the untargeted tracer in all regions of interest by the
      product of the deconvolution. Using fluorescently labeled, EGFR-targeted and
      untargeted Affibodies (known to have different blood clearance rates), the
      average tumor concentration of EGFR in four mice was estimated using dual-tracer
      kinetic modeling to be 3.9 +/- 2.4 nM compared to an expected concentration of
      2.0 +/- 0.4 nM. However, with deconvolution correction a more equivalent EGFR
      concentration of 2.0 +/- 0.4 nM was measured. 

PMID- 24743264
TI  - Phenotypic resistance and the dynamics of bacterial escape from phage control.
AB  - The canonical view of phage - bacterial interactions in dense, liquid cultures is
      that the phage will eliminate most of the sensitive cells; genetic resistance
      will then ascend to restore high bacterial densities. Yet there are various
      mechanisms by which bacteria may remain sensitive to phages but still attain high
      densities in their presence - because bacteria enter a transient state of reduced
      adsorption. Importantly, these mechanisms may be cryptic and inapparent prior to
      the addition of phage yet result in a rapid rebound of bacterial density after
      phage are introduced. We describe mathematical models of these processes and
      suggest how different types of this 'phenotypic' resistance may be elucidated. We
      offer preliminary in vitro studies of a previously characterized E. coli model
      system and Campylobacter jejuni illustrating apparent phenotypic resistance. As
      phenotypic resistance may be specific to the receptors used by phages, awareness
      of its mechanisms may identify ways of improving the choice of phages for
      therapy. Phenotypic resistance can also explain several enigmas in the ecology of
      phage-bacterial dynamics. Phenotypic resistance does not preclude the evolution
      of genetic resistance and may often be an intermediate step to genetic
      resistance. 

PMID- 24743263
TI  - Identification of cis-acting elements and splicing factors involved in the
      regulation of BIM Pre-mRNA splicing.
AB  - Aberrant changes in the expression of the pro-apoptotic protein, BCL-2-like 11
      (BIM), can result in either impaired or excessive apoptosis, which can contribute
      to tumorigenesis and degenerative disorders, respectively. Altering BIM pre-mRNA
      splicing is an attractive approach to modulate apoptosis because BIM activity is
      partly determined by the alternative splicing of exons 3 or 4, whereby exon 3
      containing transcripts are not apoptotic. Here we identified several cis-acting
      elements and splicing factors involved in BIM alternative splicing, as a step to
      better understand the regulation of BIM expression. We analyzed a recently
      discovered 2,903-bp deletion polymorphism within BIM intron 2 that biased
      splicing towards exon 3, and which also impaired BIM-dependent apoptosis. We
      found that this region harbors multiple redundant cis-acting elements that
      repress exon 3 inclusion. Furthermore, we have isolated a 23-nt intronic splicing
      silencer at the 3' end of the deletion that is important for excluding exon 3. We
      also show that PTBP1 and hnRNP C repress exon 3 inclusion, and that
      downregulation of PTBP1 inhibited BIM-mediated apoptosis. Collectively, these
      findings start building our understanding of the cis-acting elements and splicing
      factors that regulate BIM alternative splicing, and also suggest potential
      approaches to alter BIM splicing for therapeutic purposes. 

PMID- 24743265
TI  - Identification of miRNAs differentially expressed in clinical stages of human
      colorectal carcinoma-an investigation in Guangzhou, China.
AB  - Aberrant expression of microRNAs (miRNAs) has been implicated in human cancer,
      including colorectal cancer (CRC). Such dysregulated miRNAs may have potential as
      diagnostic markers or therapeutic targets. However, the nature of an association
      between these miRNAs and clinical stages of CRC is still not clear. To this end,
      we performed a miRNA profiling of 1547 distinct human miRNAs using 31 samples of
      tumor and paired normal mucosa obtained from 31 CRC patients. Based on
      statistical analyses of profiling data, we identified 569 miRNAs that were
      significantly dysregulated in CRC relative to normal tissues (P<0.05). Among the
      569 dysregulated miRNAs, downregulation of 17 was associated with stages II, III,
      and IV colon and rectal cancers (separate or combined), according to our
      criteria. We also assessed the potential of these dysregulated miRNAs as
      diagnostic biomarkers for CRC patients who were without metastasis, and the value
      of the dysregulated miRNAs for predicting metastasis, lymph node and distant.
      Their distinct expression patterns in colon and rectal cancers were also
      examined. Although our findings cannot be immediately applied toward clinical
      diagnosis, our new study model for determining and assessing the biomarker
      potential of dysregulated miRNAs should be useful in further research in
      detection of human CRC. 

PMID- 24743267
TI  - A polydnavirus ANK protein acts as virulence factor by disrupting the function of
      prothoracic gland steroidogenic cells.
AB  - Polydnaviruses are obligate symbionts integrated as proviruses in the genome of
      some ichneumonoid wasps that parasitize lepidopteran larvae. Polydnavirus free
      viral particles, which are injected into the host at oviposition, express
      virulence factors that impair immunity and development. To date, most studies
      have focused on the molecular mechanisms underpinning immunosuppression, whereas
      how viral genes disrupt the endocrine balance remains largely uninvestigated.
      Using Drosophila as a model system, the present report analyzes the function of a
      member of the ankyrin gene family of the bracovirus associated with Toxoneuron
      nigriceps, a larval parasitoid of the noctuid moth Heliothis virescens. We found
      that the TnBVank1 expression in the Drosophila prothoracic gland blocks the
      larval-pupal molt. This phenotype can be rescued by feeding the larvae with 20
      hydroxyecdysone. The localization of the TnBVANK1 is restricted to the cytoplasm
      where it interacts with Hrs and Alix marked endosomes. Collectively, our data
      demonstrate that the TnBVANK1 protein acts as a virulence factor that causes the
      disruption of ecdysone biosynthesis and developmental arrest by impairing the
      vesicular traffic of ecdysteroid precursors in the prothoracic gland
      steroidogenic cells. 

PMID- 24743266
TI  - Differing patterns of selection and geospatial genetic diversity within two
      leading Plasmodium vivax candidate vaccine antigens.
AB  - Although Plasmodium vivax is a leading cause of malaria around the world, only a
      handful of vivax antigens are being studied for vaccine development. Here, we
      investigated genetic signatures of selection and geospatial genetic diversity of
      two leading vivax vaccine antigens--Plasmodium vivax merozoite surface protein 1
      (pvmsp-1) and Plasmodium vivax circumsporozoite protein (pvcsp). Using scalable
      next-generation sequencing, we deep-sequenced amplicons of the 42 kDa region of
      pvmsp-1 (n = 44) and the complete gene of pvcsp (n = 47) from Cambodian isolates.
      These sequences were then compared with global parasite populations obtained from
      GenBank. Using a combination of statistical and phylogenetic methods to assess
      for selection and population structure, we found strong evidence of balancing
      selection in the 42 kDa region of pvmsp-1, which varied significantly over the
      length of the gene, consistent with immune-mediated selection. In pvcsp, the
      highly variable central repeat region also showed patterns consistent with immune
      selection, which were lacking outside the repeat. The patterns of selection seen
      in both genes differed from their P. falciparum orthologs. In addition, we found
      that, similar to merozoite antigens from P. falciparum malaria, genetic diversity
      of pvmsp-1 sequences showed no geographic clustering, while the non-merozoite
      antigen, pvcsp, showed strong geographic clustering. These findings suggest that
      while immune selection may act on both vivax vaccine candidate antigens, the
      geographic distribution of genetic variability differs greatly between these two
      genes. The selective forces driving this diversification could lead to antigen
      escape and vaccine failure. Better understanding the geographic distribution of
      genetic variability in vaccine candidate antigens will be key to designing and
      implementing efficacious vaccines.

PMID- 24743268
TI  - A synergism between adaptive effects and evolvability drives whole genome
      duplication to fixation.
AB  - Whole genome duplication has shaped eukaryotic evolutionary history and has been
      associated with drastic environmental change and species radiation. While the
      most common fate of WGD duplicates is a return to single copy, retained
      duplicates have been found enriched for highly interacting genes. This pattern
      has been explained by a neutral process of subfunctionalization and more
      recently, dosage balance selection. However, much about the relationship between
      environmental change, WGD and adaptation remains unknown. Here, we study the
      duplicate retention pattern postWGD, by letting virtual cells adapt to
      environmental changes. The virtual cells have structured genomes that encode a
      regulatory network and simple metabolism. Populations are under selection for
      homeostasis and evolve by point mutations, small indels and WGD. After
      populations had initially adapted fully to fluctuating resource conditions re
      adaptation to a broad range of novel environments was studied by tracking
      mutations in the line of descent. WGD was established in a minority (~30%) of
      lineages, yet, these were significantly more successful at re-adaptation.
      Unexpectedly, WGD lineages conserved more seemingly redundant genes, yet had
      higher per gene mutation rates. While WGD duplicates of all functional classes
      were significantly over-retained compared to a model of neutral losses, duplicate
      retention was clearly biased towards highly connected TFs. Importantly, no
      subfunctionalization occurred in conserved pairs, strongly suggesting that dosage
      balance shaped retention. Meanwhile, singles diverged significantly. WGD,
      therefore, is a powerful mechanism to cope with environmental change, allowing
      conservation of a core machinery, while adapting the peripheral network to
      accommodate change. 

PMID- 24743269
TI  - A synthetic community approach reveals plant genotypes affecting the phyllosphere
      microbiota.
AB  - The identity of plant host genetic factors controlling the composition of the
      plant microbiota and the extent to which plant genes affect associated microbial
      populations is currently unknown. Here, we use a candidate gene approach to
      investigate host effects on the phyllosphere community composition and abundance.
      To reduce the environmental factors that might mask genetic factors, the model
      plant Arabidopsis thaliana was used in a gnotobiotic system and inoculated with a
      reduced complexity synthetic bacterial community composed of seven strains
      representing the most abundant phyla in the phyllosphere. From a panel of 55
      plant mutants with alterations in the surface structure, cell wall, defense
      signaling, secondary metabolism, and pathogen recognition, a small number of
      single host mutations displayed an altered microbiota composition and/or
      abundance. Host alleles that resulted in the strongest perturbation of the
      microbiota relative to the wild-type were lacs2 and pec1. These mutants affect
      cuticle formation and led to changes in community composition and an increased
      bacterial abundance relative to the wild-type plants, suggesting that different
      bacteria can benefit from a modified cuticle to different extents. Moreover, we
      identified ein2, which is involved in ethylene signaling, as a host factor
      modulating the community's composition. Finally, we found that different
      Arabidopsis accessions exhibited different communities, indicating that plant
      host genetic factors shape the associated microbiota, thus harboring significant
      potential for the identification of novel plant factors affecting the microbiota
      of the communities. 

PMID- 24743271
TI  - [Significance of liver transplantation for hepatocellular carcinoma].
AB  - Liver transplantation(LT)plays a significant clinical role in the treatment of
      hepatocellular carcinoma(HCC), as it can cure not only HCC but also underlying
      liver diseases. Although various transplant criteria for HCC have been proposed,
      expanding the criteria is controversial. Extended criteria are justified when the
      recurrence rates are low. We performed retrospective analysis of 136 HCC patients
      who underwent living donor LT(LDLT)at our center between February 1999 and
      December 2006 to examine the risk factors for post-transplant recurrence. Based
      on the results of our multivariate analysis, we defined new criteria, which we
      call the Kyoto criteria. The new criteria are as follows: nC10, tumor diameter C5
      cm, and serum desgamma- carboxy prothrombin levels of C400mAU/mL. The 5-year
      recurrence rate for patients who met the Kyoto criteria was significantly lower
      than that for patients who exceeded these criteria(3% vs 56%, p<0.001). This
      demonstrates that the Kyoto criteria can effectively exclude patients with
      biologically aggressive tumors prior to transplantation. We began to implement
      the Kyoto criteria in January 2007 and have started a prospective study to
      validate the feasibility of these criteria. As of December 2011, 62 patients with
      HCC have undergone LDLT. These patients had a 5-year overall survival rate of
      82%, and a recurrence rate of 6%. Considering the higher morbidity and mortality
      rates associated with LT compared to those for other treatment modalities for HCC
      as well as risks to live donors, LDLT is better used as a second-line treatment
      option for HCC. 

PMID- 24743272
TI  - [Leukemia stem cell].
AB  - Cancer is the main cause of death in advanced countries. It has become
      progressively clear that cancer cells are distributed in a developmental
      hierarchy, in which whole cancer tissues originate from cancer stem cells(CSCs).
      CSCs were first discovered in a case of acute myeloid leukemia. Leukemia stem
      cells(LSCs)are resistant to conventional chemotherapies because of their dormancy
      and are therefore the cause of minimal residual disease and relapse. Many
      investigators are working to develop novel therapeutic strategies for eliminating
      LSCs. LSC biology is discussed in the first part of this review, and the
      therapeutic approach to LSC targeting is described in the latter part. 

PMID- 24743273
TI  - [The intestinal epithelial stem cells and cancer stem cells].
AB  - Intestinal mucosa is renewed throughout life in a repeating cycle of
      proliferation, differentiation, and cell death. Intestinal stem cells play a very
      important role in the maintenance of the intestinal environment, which is
      frequently exposed to various factors such as food, infections, microbiota
      elements, drugs, and metabolic products. Therefore, identification of intestinal
      epithelial stem cells might help in understanding intestinal regulation. On the
      other hand, dividing intestinal stem cells may, by an unknown mechanism, give
      rise to cancer stem cells that cause the various malignant types of colon cancer.
      In this paper, current developments in the study of the regulation of both
      intestinal stem cells and cancer stem cells are reviewed. 

PMID- 24743270
TI  - Genome and transcriptome analysis of the fungal pathogen Fusarium oxysporum f.
      sp. cubense causing banana vascular wilt disease.
AB  - BACKGROUND: The asexual fungus Fusarium oxysporum f. sp. cubense (Foc) causing
      vascular wilt disease is one of the most devastating pathogens of banana (Musa
      spp.). To understand the molecular underpinning of pathogenicity in Foc, the
      genomes and transcriptomes of two Foc isolates were sequenced.
      METHODOLOGY/PRINCIPAL FINDINGS: Genome analysis revealed that the genome
      structures of race 1 and race 4 isolates were highly syntenic with those of F.
      oxysporum f. sp. lycopersici strain Fol4287. A large number of putative virulence
      associated genes were identified in both Foc genomes, including genes putatively
      involved in root attachment, cell degradation, detoxification of toxin,
      transport, secondary metabolites biosynthesis and signal transductions.
      Importantly, relative to the Foc race 1 isolate (Foc1), the Foc race 4 isolate
      (Foc4) has evolved with some expanded gene families of transporters and
      transcription factors for transport of toxins and nutrients that may facilitate
      its ability to adapt to host environments and contribute to pathogenicity to
      banana. Transcriptome analysis disclosed a significant difference in
      transcriptional responses between Foc1 and Foc4 at 48 h post inoculation to the
      banana 'Brazil' in comparison with the vegetative growth stage. Of particular
      note, more virulence-associated genes were up regulated in Foc4 than in Foc1.
      Several signaling pathways like the mitogen-activated protein kinase Fmk1
      mediated invasion growth pathway, the FGA1-mediated G protein signaling pathway
      and a pathogenicity associated two-component system were activated in Foc4 rather
      than in Foc1. Together, these differences in gene content and transcription
      response between Foc1 and Foc4 might account for variation in their virulence
      during infection of the banana variety 'Brazil'. CONCLUSIONS/SIGNIFICANCE: Foc
      genome sequences will facilitate us to identify pathogenicity mechanism involved
      in the banana vascular wilt disease development. These will thus advance us
      develop effective methods for managing the banana vascular wilt disease,
      including improvement of disease resistance in banana.

PMID- 24743274
TI  - [Molecular mechanisms of stem cell disorders - microRNAs and epigenetics].
AB  - Stem cells are characterized by their ability to self-renew and differentiate
      into cells in the tissues, and have an important role in the maintenance of
      tissues and/or organs. Even in cancers in which accumulated gene mutations drive
      the abnormalities in cell proliferation and differentiation, the presence of stem
      cells, called cancer stem cells, has been proposed. Current observations suggest
      that cancer stem cells have properties reminiscent of normal stem cells and have
      pivotal roles in tumor development, recurrence, and metastasis. Because cells in
      a multicellular organism contain basically the same genetic information, the
      mechanisms that regulate gene expression, such as microRNAs and epigenetics, are
      critical for the proper differentiation of stem cells. Indeed, studies have shown
      that cooperative interactions between microRNAs and epigenetics regulate stem
      cell properties. We have previously reported that the microRNAs in the miR-200
      clusters are coordinately downregulated in human breast cancer stem cells and
      normal breast stem cells. Among them, miR-200c targets the Polycomb group protein
      BMI1, a critical regulator of stem cell functions. The expression of the miR-200
      precursor is regulated by histone modifications and Polycomb group proteins.
      Moreover, miR-22 targets a DNA demethylase and suppresses the expression of the
      miR-200 precursor, thereby enhances the expression of BMI1. Considering the
      recent development of therapies that target cancer stem cells and/or epigenetics,
      understanding the molecular mechanisms for stem cell regulation is becoming
      increasingly important. 

PMID- 24743275
TI  - [Evaluation of recurrence rates on change in hormone receptor and human epidermal
      growth factor receptor 2 status after neo-adjuvant chemotherapy in breast cancer
      patients].
AB  - BACKGROUND: Neo-adjuvant chemotherapy(NAC)may affect hormone receptor(HR)and
      human epidermal growth factor receptor 2(HER2)status in breast cancer patients.
      However, the correlation between recurrence rates and this status change remains
      unclear. METHODS: We evaluated 70 consecutive breast cancer patients receiving
      NAC with anthracyclines and taxanes, with or without trastuzumab, between January
      2005 and May 2012. Pre-treatment core needle biopsy samples and specimens
      obtained after surgery were tested to determine HR and HER2 status. The
      relationship between HR and HER2 status changes and recurrence rates was then
      assessed. RESULTS: Pathological complete response(pCR)was observed in 13 cases
      and non-pCR was observed in 57 cases. Of the non-pCR cases, HR-positive status
      changed to HR-negative status in 6.3% of patients, but a change from negativity
      to positivity was not observed. HER2-positive status changed to HER2-negative
      status in 48.0% of patients, and a change from negativity to positivity was
      observed in 12.5% of cases. The recurrence rate among patients with conversion to
      a HR-negative status was 0%and that among patients with conversion to a HER2
      negative status was 25.0%. CONCLUSION: Recurrence rates were not significantly
      associated with HR and HER2 status conversion after NAC. Future research is
      warranted to confirm out results.

PMID- 24743276
TI  - [Cis-diamminedichloroplatinum penetration into the cerebrospinal fluid of the
      lateral ventricle, postoperative cavity, and lumbar subarachnoid space with or
      without pre-intravenous mannitol administration in patients with brain metastasis
      from lung cancer].
AB  - We have previously reported that repeated intravenous administration of cis
      diamminedichloroplatinum(CDDP)prevented local recurrence of metastatic brain
      tumors after surgical total excision; however, data on CDDP distribution in the
      postoperative cavity after intravenous CDDP administration are not available. In
      the present study, we evaluated the penetration of total platinum(Pt)into the
      cerebrospinal fluid(CSF)and the effect of intravenous administration of
      20%mannitolon total Pt distribution in the plasma and CSF. Total Pt levels in the
      plasma and CSF were determined immediately after intravenous infusion of
      CDDP(80mg/m2)for 1 hour, with or without pre-intravenous infusion of 20%
      mannitol(200mL), in 11 patients with brain metastasis from lung cancer. CSF
      samples were obtained via Ommaya reservoirs placed in the anterior horn of the
      lateral ventricle(CSF-V)and the postoperative cavity(CSF-C). Spinal CSF (CSF
      L)was also obtained in the last 4 patients of the series via spinal drainage.
      CDDP was administered intravenously without mannitol 10 days after brain tumor
      excision, and 1 week after the initial administration of CDDP, CDDP was
      intravenously administered again after intravenous mannitol administration. CDDP
      was always administered intravenously at 1:00 PM to rule out the influence of
      circadian variation. Plasma and CSF were sequentially sampled after intravenous
      CDDP administration, and their Pt levels were analyzed for Pt content by using
      atomic absorption spectroscopy. The area under the concentration time
      curve(AUC)was calculated for plasma and CSF using the moment method. The AUC for
      total Pt in plasma showed a significantly higher level with the administration of
      mannitol than without the administration of mannitol(p<0.01, paired t-test).
      Total Pt levels(AUCs and peak concentrations)in CSF-C were much higher than were
      those in CSF-V and CSF-L both with and without the administration of mannitol.
      The ratio(%)of CDDP penetration into CSF(CSF AUC/plasma AUC)was much higher for
      CSF-C than for CSF-V(p<0.0001)both with and without mannitol administration.
      However, the CSF penetration ratio with mannitol administration did not differ
      significantly from that without mannitol administration. Thus, the administration
      of mannitol did not significantly increase the penetration ratio of total Pt.
      Creatinine clearance was moderately reduced in all patients during the first
      administration of CDDP. However, 7 of the 11 patients showed an increase in
      creatinine clearance after the second administration of CDDP with mannitol.

PMID- 24743277
TI  - [Using electronic medical records to identify outpatients receiving opioids who
      may benefit from intervention by our palliative care team].
AB  - OBJECTIVE: To achieve optimal management of cancer pain in our outpatients.
      PATIENTS: All cancer patients in our outpatient department who received opioids.
      METHOD: A pharmacist and a nurse of the palliative care team used electronic
      medical records(EMRs)to review cases of outpatients who received opioids. RESULT:
      A total of 136 cases were followed-up by our palliative care team based on EMRs
      from May 2010 to January 2011. Our palliative care team intervened in 50 of these
      cases (36.8%). Doctors and nurses were given questionnaires to assess the
      usefulness of this practice, and 60% of the doctors and 65.2% of the nurses, had
      useful rounds. CONCLUSION: In this trial, we conclude that the use of EMRs to
      identify patients for intervention by our palliative care team is beneficial to
      our medical care system, which improves the quality of life of our patients.

PMID- 24743278
TI  - [Effectiveness of mirtazapine for digestive symptoms in palliative care -
      retrospective study of 50 cases].
AB  - BACKGROUND: Previous research has reported that mirtazapine, a 5-HT3 antagonist,
      is effective for alleviation of digestive symptoms. PURPOSE: To elucidate the
      effect of low-dose mirtazapine on digestive symptoms. PATIENTS AND METHODS:
      Mirtazapine was administered to 50 cancer patients with digestive symptoms in
      palliative care, and the data were retrospectively examined. The initial doses
      ranged from 1.875 to 7.5 mg, and were increased to a maintenance dose according
      to its effects and the degree of somnolence. RESULTS: The cases were divided into
      2 groups based on the cause of the digestive symptoms, including unknown
      causes(27 cases)and chemotherapy and/or opioid treatment(23 cases). At the
      initial dose, the efficacy rate was 74.4%, and the effectiveness was
      significantly higher in patients whose symptoms were due to chemotherapy and/ or
      opioid use than in those with symptoms of unknown cause(p=0.008). The rate of
      somnolence was 29.5%. Discontinuation of treatment within 1 week occurred in 10
      cases. In 40 cases that continued administration of the maintenance dose, the
      efficacy rate was 82.5%, and the increased doses provided relief in the patient
      group with digestive symptoms of unknown cause. CONCLUSIONS: Low-dose mirtazapine
      showed different effects depending on the cause of digestive symptoms; therefore,
      the dose should be increased in patients whose symptoms are of unknown cause.
      Somnolence often appeared even at a low-dose, and this should be taken into
      consideration in the palliative care setting.

PMID- 24743279
TI  - [Evaluation of the antiemetic effect of aprepitant in lung cancer patients
      receiving carboplatin-based chemotherapy using the Functional Living Index-Emesis
      questionnaire].
AB  - In the present study, we evaluated the antiemetic effect of aprepitant in
      combination with 5-hydroxytryptophan(5-HT3) receptor antagonist and dexamethasone
      for chemotherapy-induced emesis and nausea in lung cancer patients treated with
      carboplatin-based systemic chemotherapy using the Functional Living Index-Emesis,
      an emesis- and nausea-specific quality of life(QOL)questionnaire. Patients
      experiencing emesis and/or nausea during and/or after previous courses of
      carboplatin-based chemotherapy received aprepitant in the following treatment
      cycle with the same anti-cancer agent. Emesis- and nausea-specific QOL aspects
      were significantly improved with the addition of aprepitant to the existing
      regimen containing dexamethasone and 5-HT3 receptor antagonist. Our result
      suggests that combined antiemetic treatment with aprepitant, dexamethasone, and 5
      HT3 receptor antagonist is more effective in lung cancer patients receiving
      carboplatin-based systemic chemotherapy than dexamethasone and 5-HT3 receptor
      antagonist alone.

PMID- 24743280
TI  - [Comparative evaluation of 2 antiemesis tools for the prevention of chemotherapy
      induced nausea and vomiting].
AB  - Although recent advances in chemotherapy have led to improved quality of
      life(QOL)and prolonged survival in patients with advanced cancer, treatment is
      often discontinued because of adverse events associated with chemotherapy,
      regardless of its efficacy.Nevertheless, chemotherapy has been validated in the
      United States and United Kingdom and is used worldwide. In Japan, few reports
      have been published regarding the use of assessment tools including the
      Multinational Association of Supportive Care in Cancer(MASCC)Antiemesis
      Tool(MAT)for the evaluation of chemotherapy-induced nausea and vomiting(CINV).We
      prospectively investigated the utility of the MAT and digestive symptom
      diary(DSD).In total, 68 patients who underwent highly and moderately emetogenic
      chemotherapy were included in the efficacy analyses.The improvement in the
      control of CINV during the delayed phase was significantly different between the
      DSD and MAT groups(p= 0.0148).The results obtained using the MAT warrant further
      validation.Meanwhile, the DSD may be used as an information tool by medical staff
      and patients. 

PMID- 24743281
TI  - [Clinical evaluation of lapatinib therapy in metastatic breast cancer using the
      Bayes meta-analysis].
AB  - The efficacy of treatments involving lapatinib for patients with metastatic
      breast cancers was evaluated in a Bayesian metaanalysis of published data from
      randomized controlled clinical trials. Four randomized controlled trials
      including 2,708 patients met the inclusion criteria. Among these patients, 568
      were positive for the human epidermal growth factor receptor 2(HER2). The
      clinical benefit rate(CBR)for HER2-positive patients was the primary outcome of
      the analysis, and the overall survival(l OS) and the number needed to
      treat(NNT)were the secondary outcomes of the reported meta-analysis. The Bayesian
      metaanalysis was conducted according to the Markov-chain Monte-Carlo technique in
      WinBUGS. The CBR for HER2-positive patients was significantly improved(odds
      ratio[OR]: 2.281, 95% confidence interval[CI]: 1.490-3.628), whereas no
      statistically significant improvement was seen in the overall patient CBR(OR:
      1.559, 95% CI: 0.768-3.238). The OS hazard ratio (HR)and NNT for the CBR were
      also estimated for HER2-positive patients. The difference in the OS HR was not
      statistically significant(HR: 0.789, 95% CI: 0.556-1.086)for HER2-positive
      patients. The improvement in the NNT for the CBR was statistically
      significant(NNT 5.164, 95% CI: 3.803-8.723)for HER2-positive patients.

PMID- 24743282
TI  - [A case of trastuzumab-resistant breast cancer responding to
      lapatinib/capecitabine therapy].
AB  - Here we report a case of a 56-year-old woman who presented at our hospital with a
      chief complaint of a red lump in her right breast. Breast cancer(Rt C, T4bN0M0;
      ER[-], PgR[-], HER2: 3[+]; stage IIIb)was diagnosed, and subsequent preoperative
      chemotherapy, mastectomy and axillary lymph node dissection were performed. Five
      months after surgery, bone metastasis in the thoracolumbar vertebrae developed
      and trastuzumab/zoledronic acid hydrate therapy was initiated. Four months after
      the therapy, tumor marker levels increased and docetaxel was added to the
      treatment regimen. Although the patient's condition temporarily improved, tumor
      marker levels increased again after 6 months, and the treatment regimen was
      switched to trastuzumab/nab-paclitaxel therapy. However, such regimen was
      discontinued owing to the development of liver metastasis, and
      lapatinib/capecitabine therapy was initiated. Two months after
      lapatinib/capecitabine therapy, tumor marker levels normalized and the liver
      metastasis markedly reduced. Side effects included paronychia(grade 3), which
      improved with dose reduction. The patient's therapy is being continued. 

PMID- 24743283
TI  - [A case of local recurrence developing thirty-nine years after mastectomy for
      breast cancer].
AB  - Here we report a case of breast cancer that recurred after a 39-year latency
      period. A 73-year-old woman,who had undergone radical mastectomy for left breast
      cancer 39 years previously,consulted our hospital complaining of lymphedema in
      the left arm. A computed tomography(CT)scan showed a growth of soft tissue in the
      left chest wall. A core needle biopsy resulted in the pathological diagnosis of
      metastatic adenocarcinoma,which stained positively for estrogen and progesterone
      receptors,but not for human epidermal growth factor receptor 2(HER2). Diagnosed
      with local recurrence of breast cancer, the patient was consequently treated with
      hormone therapy using anastrozole and achieved a partial response. The patient is
      currently free from further recurrent disease at 7 months. We report this late
      recurrence of breast cancer 39 years following mastectomy,suggesting that
      possible recurrence of this disease with more than a 30-year latency period
      should be taken into consideration. 

PMID- 24743284
TI  - [A case of malignant peritoneal mesothelioma with the epithelioid histological
      type, successfully treated with pemetrexed plus cisplatin].
AB  - A 45-year-old man presented with severe abdominal distention with massive ascites
      due to a diffusely disseminated peritoneal tumor. A core needle biopsy specimen
      was obtained from the peritoneal lesion. Histological diagnosis was epithelioid
      type mesothelioma. He did not choose to receive chemotherapy. For 2.5 years, he
      went without medical intervention, and his disease gradually progressed, leading
      to a worsening of his symptoms. The patient then chose to be treated with
      combination chemotherapy of cisplatin and pemetrexed, followed by pemetrexed
      alone. There was remarkable tumor shrinkage and his symptoms improved. These
      effects have been sustained for two years after the initial chemotherapy.
      Chemotherapy appears to have contributed to survival prolongation for this
      patient. This case exemplifies the fact that malignant peritoneal mesothelioma
      may progress slowly when fits with some good prognostic factors, and it is
      important to consider the prognostic factors.

PMID- 24743285
TI  - [A case of breast cancer with repeated cardiac dysfunction due to trastuzumab].
AB  - Here we present a case of breast cancer in which cardiac dysfunction had
      previously been observed on trastuzumab(TRS) administration; the condition then
      improved but reoccurred on readministration of TRS. A 52-year-old woman received
      preoperative chemotherapy for StageIIIC left breast cancer(fluorouracil,
      epirubicin and cyclophosphamide followed by docetaxel and TRS), and then
      underwent partial mastectomy and axillary lymph node dissection. For adjuvant
      therapy, she received endocrine therapy and TRS. Radiation therapy was
      administered to the left residual breast. The patient complained about
      palpitation in the 5th cycle of TRS, and left ventricle ejection
      fraction(LVEF)decreased to 45.3% from 64%. Therefore, we stopped TRS
      administration. Palpitation improved, and LVEF increased to 53% after 2 months.
      TRS was administered again; however, palpitation reoccurred and LVEF decreased to
      44%. TRS administration was once again discontinued. However, according to the
      HERA trial report regarding patients with a history of anthracycline and
      radiation therapy, TRS administration could be resumed when LVEF is greater than
      50%, but we should be more careful during readministration of TRS.

PMID- 24743286
TI  - [A case of large cell neuroendocrine carcinoma of the stomach with liver
      metastasis effectively treated with S-1 and CDDP combination therapy].
AB  - A 73-year-old man was referred to our hospital because of appetite loss and
      weight loss in January 2009. Endoscopy showed an advanced type II gastric tumor
      at the middle of the gastric wall, and computed tomography showed multiple liver
      metastases. Immunohistological examination confirmed a diagnosis of large cell
      neuroendocrine carcinoma which was chromogranin A(+), CD56(+), and
      synaptophysin(+). Oral administration of S-1(100mg/body)was given 5 days on and 2
      days off, while cisplatin(CDDP 40 mg/body)was administered intravenously once
      every 2 weeks. The patient achieved a partial response(PR), and no serious
      adverse effects were observed. This case suggests that S-1/CDDP chemotherapy may
      be an effective treatment in patients with large cell neuroendocrine carcinoma of
      the stomach.

PMID- 24743287
TI  - [A case report of two-term surgery for focal progression of a huge liver
      metastasis and peritoneal dissemination from gastrointestinal stromal tumor
      during imatinib mesylate treatment].
AB  - We report a patient who underwent 2-term surgery to treat focal progression of a
      huge liver metastasis and peritoneal dissemination from a gastric
      gastrointestinal stromal tumor(GIST)during imatinib mesylate treatment. A 59-year
      old man underwent an emergency surgery for perforative peritonitis caused by
      gastric GIST in June 2006 and a partial resection of the stomach in September
      2006. Four years later, abdominal computed tomography(CT)detected a huge liver
      tumor that occupied the entire right lobe. We initiated imatinib mesylate
      treatment(400mg/day), and the patient maintained stable disease for several
      months. However, focal progression of the huge liver tumor and a peritoneal tumor
      at the splenic hilum were revealed by CT; therefore, an extended right hepatic
      resection was performed in August 2011 and a distal pancreatectomy, splenectomy,
      and partial resection of the stomach were performed in February 2012. The patient
      died of the primary disease at 16 months after the hepatic resection for focal
      progression.

PMID- 24743288
TI  - [Long-term survival in a case of recurrent gastrointestinal stromal tumor treated
      with intermittent or low-dose imatinib].
AB  - A 65-year-old woman with a gastrointestinal stromal tumor(GIST)underwent a total
      gastrectomy in 1999. In 2004, she was diagnosed with an intra-abdominal
      recurrence and was treated with 300mg/day of imatinib. Because of the side
      effects of imatinib, we interrupted the treatment and were forced to reduce the
      dose from 300mg/day to 100mg/day. However, at present, the tumor remains
      controlled. In conclusion, this case suggested that, even if given irregularly or
      at a low-dose, continuous treatment with imatinib might contribute to long-term
      survival in patients with GIST.

PMID- 24743289
TI  - [A case of Stage IV sigmoid colon cancer that achieved long-term survival with
      oral anticancer drugs].
AB  - An 80-year-old man presenting with abdominal distension was admitted to our
      hospital. He was diagnosed with sigmoid cancer with multiple liver and lung
      metastases. We first performed a sigmoidectomy to avoid obstruction, and then
      initiated chemotherapy with S-1(120mg/day). The tumor showed a complete clinical
      response after 10 courses, but we had to change the regimen after 18 courses
      because of growth of the lung metastases. After 10 courses of
      capecitabine(4,200mg/ day)treatment, we again observed growth of the lung
      metastases; a new nodule, which was also considered to be a metastasis, appeared
      on the abdominal wall. We then decided to administer mFOLFOX6(5
      fluorouracil+Leucovorin+oxaliplatin) after the patient had received oral
      anticancer drugs for 3 years 4 month. In conclusion, oral chemotherapy drugs may
      prevent tumor growth over a long period and improve quality of life(QOL)in
      elderly patients with Stage IV colon cancer. 

PMID- 24743290
TI  - [A case of sigmoid colon cancer with a sigmoidovesical fistula treated with
      preoperative XELOX+bevacizumab therapy and urinary bladder-conserving surgery].
AB  - A 64-year-old man presented with abdominal pain, diarrhea, urinary pain, and
      frequent urination.He was diagnosed with locally advanced sigmoid colon cancer
      accompanied by a sigmoidovesical fistula, which was determined to require total
      cystectomy for curative resection.Expecting tumor shrinkage and conservation of
      the urinary bladder, we performed loop ileostomy followed by preoperative
      mFOLFOX6+bevacizumab therapy.After 1 course of administration, the implanted port
      became infected.Therefore, the regimen was changed to 4 courses of
      XELOX+bevacizumab therapy.After the treatment, there was no longer any evidence
      of sigmoidovesical fistula.We performed a urinary bladder-conserving
      sigmoidectomy and finally achieved pathological curative resection.After adjuvant
      chemotherapy, no findings suggestive of recurrence were noted during 10
      postoperative months.Preoperative XELOX+bevacizumab therapy may be worth
      considering as a therapeutic option for conserving the urinary bladder in cases
      of locally advanced colon cancer.

PMID- 24743291
TI  - [A case of gastrointestinal stromal tumor of the jejunum successfully treated by
      preoperative induction chemotherapy with imatinib mesylate administered through
      jejunostomy and subsequent surgical resection].
AB  - A 70 -year-old female patient with a palpable mass in the left upper abdomen
      suffered from abdominal pain and fever. Abdominal computed tomography showed a
      jejunal tumor 11 cm in diameter with ascites, suggesting rupture of the tumor.
      Histological diagnosis via endoscopic ultrasound-guided fine needle aspiration
      indicated c-kit-positive gastrointestinal stromal tumor. Diagnostic laparoscopy
      demonstrated a large jejunal tumor possibly invading the stomach and pancreas.
      The patient then underwent tube jejunostomy. Thereafter, preoperative induction
      chemotherapy with imatinib mesylate(400mg/ body/day)via jejunostomy was
      administered for 6 months, resulting in 20%reduction of the tumor diameter and
      disappearance of any indication of stomach and pancreas invasion. The patient
      then underwent radical partial resection of the jejunum without combined
      resection of either the stomach or pancreas. Postoperative adjuvant chemotherapy
      with imatinib mesylate (400mg/body/day)was also indicated. No sign of recurrence
      has been detected to date after 1 year of follow-up.

PMID- 24743292
TI  - [Induction chemotherapy with S-1/oxaliplatin prevented colostomy in a patient
      with advanced rectal cancer].
AB  - A 72-year-old woman was admitted to our hospital with bloody stools and
      constipation. She was diagnosed with advanced lower rectal cancer with multiple
      liver and pulmonary metastases. Because the rectal cancer was located 2 cm from
      the anal verge, we suggested she undergo an abdominoperineal resection(Miles
      operation), but she refused to undergo a colostomy. Then, 6 courses of
      chemotherapy with S-1/oxaliplatin(SOX)were administered, and the local tumor,
      liver metastases, and pulmonary metastases were all significantly decreased in
      size(reduction rate 60%). After chemotherapy, she chose to undergo low anterior
      resection(LAR), D2. Postoperative recovery was uneventful, and she currently has
      stable disease with adjuvant SOX chemotherapy. Induction SOX chemotherapy was
      considered to be useful for maintaining the quality of life(QOL) in a patient
      with advanced rectal cancer. 

PMID- 24743293
TI  - [A case of curatively resected sigmoid colon cancer after mFOLFOX6 plus
      panitumumab neoadjuvant chemotherapy].
AB  - A 54-year-old man with residual urine, abdominal pain, and a high fever was
      diagnosed with KRAS wild-type sigmoid colon cancer with urinary bladder invasion.
      Considering the difficulty of curative resection, we first performed an
      ileostomy. Remarkable tumor regression was indicated by computed
      tomography(CT)and colonoscopy after 3 courses of mFOLFOX6 plus panitumumab. A
      sigmoidectomy and partial cystectomy were performed with a curative intent. Six
      courses of XELOX adjuvant chemotherapy were administered, and no recurrence has
      been observed for 9 months. mFOLFOX6 plus panitumumab might be an effective
      preoperative chemotherapy for patients with locally advanced KRAS wild-type colon
      cancer. 

PMID- 24743294
TI  - Gait initiation in children with Rett syndrome.
AB  - Rett syndrome is an X-linked neurodevelopmental condition mainly characterized by
      loss of spoken language and a regression of purposeful hand use, with the
      development of distinctive hand stereotypies, and gait abnormalities. Gait
      initiation is the transition from quiet stance to steady-state condition of
      walking. The associated motor program seems to be centrally mediated and includes
      preparatory adjustments prior to any apparent voluntary movement of the lower
      limbs. Anticipatory postural adjustments contribute to postural stability and to
      create the propulsive forces necessary to reach steady-state gait at a predefined
      velocity and may be indicative of the effectiveness of the feedforward control of
      gait. In this study, we examined anticipatory postural adjustments associated
      with gait initiation in eleven girls with Rett syndrome and ten healthy subjects.
      Muscle activity (tibialis anterior and soleus muscles), ground reaction forces
      and body kinematic were recorded. Children with Rett syndrome showed a
      distinctive impairment in temporal organization of all phases of the anticipatory
      postural adjustments. The lack of appropriate temporal scaling resulted in a
      diminished impulse to move forward, documented by an impairment in several
      parameters describing the efficiency of gait start: length and velocity of the
      first step, magnitude and orientation of centre of pressure-centre of mass vector
      at the instant of (swing-)toe off. These findings were related to an abnormal
      muscular activation pattern mainly characterized by a disruption of the
      synergistic activity of antagonistic pairs of postural muscles. This study showed
      that girls with Rett syndrome lack accurate tuning of feedforward control of
      gait. 

PMID- 24743295
TI  - Provider-initiated HIV testing and counselling in Rwanda: acceptability among
      clinic attendees and workers, reasons for testing and predictors of testing.
AB  - INTRODUCTION: Routine provider-initiated HIV testing and counselling (PITC) may
      increase HIV testing rates, but whether PITC is acceptable to health facility
      (HF) attendees is unclear. In the course of a PITC intervention study in Rwanda,
      we assessed the acceptability of PITC, reasons for being or not being tested and
      factors associated with HIV testing. METHODS: Attendees were systematically
      interviewed in March 2009 as they left the HF, regarding knowledge and
      acceptability of PITC, history of testing and reasons for being tested or not.
      Subsequently, PITC was introduced in 6 of the 8 HFs and a second round of
      interviews was conducted. Independent factors associated with testing were
      analysed using logistic regression. Randomly selected health care workers (HCWs)
      were also interviewed. RESULTS: 1772 attendees were interviewed. Over 95% agreed
      with the PITC policy, both prior to and after implementation of PITC policy. The
      most common reasons for testing were the desire to know one's HIV status and
      having been offered an HIV test by an HCW. The most frequent reasons for not
      being tested were known HIV status and test not being offered. In multivariable
      analysis, PITC, age >=15 years, and not having been previously tested were
      factors significantly associated with testing. Although workload was increased by
      PITC, HIV testing rates increased and HCWs overwhelmingly supported the policy.
      CONCLUSION: Among attendees and HCWs in Rwandan clinics, the acceptability of
      PITC was very high. PITC appeared to increase testing rates and may be helpful in
      prevention and early access to treatment.

PMID- 24743296
TI  - GhMPK17, a cotton mitogen-activated protein kinase, is involved in plant response
      to high salinity and osmotic stresses and ABA signaling.
AB  - Mitogen-activated protein kinase (MAPK) cascades play pivotal roles in mediating
      biotic and abiotic stress responses. Cotton (Gossypium hirsutum) is the most
      important textile crop in the world, and often encounters abiotic stress during
      its growth seasons. In this study, a gene encoding a mitogen-activated protein
      kinase (MAPK) was isolated from cotton, and designated as GhMPK17. The open
      reading frame (ORF) of GhMPK17 gene is 1494 bp in length and encodes a protein
      with 497 amino acids. Quantitative RT-PCR analysis indicated that GhMPK17
      expression was up-regulated in cotton under NaCl, mannitol and ABA treatments.
      The transgenic Arabidopsis plants expressing GhMPK17 gene showed higher seed
      germination, root elongation and cotyledon greening/expansion rates than those of
      the wild type on MS medium containing NaCl, mannitol and exogenous ABA,
      suggesting that overexpression of GhMPK17 in Arabidopsis increased plant ABA
      insensitivity, and enhanced plant tolerance to salt and osmotic stresses.
      Furthermore, overexpression of GhMPK17 in Arabidopsis reduced H2O2 level and
      altered expression of ABA- and abiotic stress-related genes in the transgenic
      plants. Collectively, these data suggested that GhMPK17 gene may be involved in
      plant response to high salinity and osmotic stresses and ABA signaling.

PMID- 24743297
TI  - Diagnostic imaging of the nasolacrimal drainage system. Part I. Radiological
      anatomy of lacrimal pathways. Physiology of tear secretion and tear outflow.
AB  - Excessive watering of the eye is a common condition in ophthalmological practice.
      It may be the result of excessive production of tear fluid or obstruction and
      insufficiency of efferent tear pathways. The differentiation between obstruction
      and insufficiency of the lacrimal pathways is still clinically questionable. In
      the diagnostic process it is necessary to perform clinical tests and additional
      diagnostic imaging is often needed. Dacryocystography, with or without the
      extension of the dynamic phase or subtraction option, still remains the criterion
      standard for diagnostic imaging of the lacrimal obstruction. It may help to
      clarify the cause and exact place of the obstruction and provide information for
      further management, especially surgical treatment. Increasingly, new techniques
      are used in diagnostic imaging of the lacrimal tract, such as computed
      tomography, magnetic resonance, and isotopic methods. Adequate knowledge of the
      anatomy and physiology of the lacrimal system and the secretion and outflow of
      tears is the basis for proper diagnostic imaging. The purpose of this paper is to
      present the exact anatomy of the lacrimal system, with particular emphasis on the
      radiological anatomy and the current state of knowledge about the physiology of
      tear secretion and drainage.

PMID- 24743298
TI  - Current assessment and treatment strategies of dysphagia in head and neck cancer
      patients: a systematic review of the 2012/13 literature.
AB  - PURPOSE OF REVIEW: Dysphagia, or swallowing impairment, is a serious sequel of
      head and neck cancer (HNC) and its treatment. This review focuses on the rapidly
      growing literature published during the past 2 years about the current assessment
      and treatment strategies of dysphagia in HNC patients. RECENT FINDINGS:
      Functional swallowing assessment has become standard of care in many HNC centers,
      to prevent or identify (silent) aspiration, to optimize functional outcomes, and
      to determine the appropriate rehabilitation strategy. Also preventive swallowing
      exercises are considered more and more in the pretreatment setting with promising
      results on (pharyngeal) swallowing function. However, there is a lack of
      consensus regarding type, frequency, or intensity of the exercises. Furthermore,
      long-term follow-up of swallowing function might be necessary, given the
      potential for long-term sequels following HNC treatment. SUMMARY: Regarding
      dysphagia evaluation, there is still a lack of a uniform 'gold-standard' for both
      assessment and treatment strategies. More high-quality data, adequately
      controlled, adequately powered and randomized, on prophylactic and therapeutic
      swallowing exercises are needed, with longer follow-up and better adherence to
      treatment, for better understanding the effects of chemo and radiotherapy dosage,
      and of frequency, timing and duration of treatment, to improve swallowing
      function and optimize quality of life.

PMID- 24743299
TI  - Can the oral microflora affect oral ulcerative mucositis?
AB  - PURPOSE OF REVIEW: Oral mucositis is one of the most prevalent toxicities after
      hematopoietic stem cell transplantation. Mucositis is initiated by the
      chemotherapy or radiotherapy preceding the transplantation. It is commonly
      accepted that microorganisms play a role in the process of oral mucositis.
      Despite the upcoming techniques to determine the whole oral bacterial ecosystem,
      the exact role of the microflora in mucositis is not yet understood. This article
      provides an overview of the state-of-the-art research on the oral microflora and
      mucositis. RECENT FINDINGS: A shift in microflora, in both the intestine and the
      oral cavity, can be found after chemotherapy or radiation therapy. The presence
      of oral ulcerative mucositis coincides with the presence of periodontitis
      associated bacteria, in particular Porphyromonas gingivalis. Moreover, this
      bacterium can inhibit wound healing processes in an in-vitro model. SUMMARY: We
      come to realize that some diseases are associated with a shift in the microflora.
      The role of the microflora in oral and intestinal mucositis is gaining more
      attention in recent literature. In the oral cavity, periodontitis-associated
      bacteria may influence the healing of ulcerations and the role they play in
      mucositis may be more subtle and complicated than was previously thought.

PMID- 24743300
TI  - Attenuation of experimental colitis in glutathione peroxidase 1 and catalase
      double knockout mice through enhancing regulatory T cell function.
AB  - Reactive oxygen species (ROS) have been implicated in the progression of
      inflammatory diseases including inflammatory bowel diseases (IBD). Meanwhile,
      several studies suggested the protective role of ROS in immune-mediated
      inflammatory diseases, and it was recently reported that dextran sodium sulfate
      (DSS)-induced colitis was attenuated in mice with an elevated level of ROS due to
      deficiency of peroxiredoxin II. Regulatory T cells (Tregs) are critical in the
      prevention of IBD and Treg function was reported to be closely associated with
      ROS level, but it has been investigated only in lowered levels of ROS so far. In
      the present study, in order to clarify the relationship between ROS level and
      Treg function, and their role in the pathogenesis of IBD, we investigated mice
      with an elevated level of ROS due to deficiency of both glutathione peroxidase
      (GPx)-1 and catalase (Cat) for the susceptibility of DSS-induced colitis in
      association with Treg function. The results showed that DSS-induced colitis was
      attenuated and Tregs were hyperfunctional in GPx1-/- * Cat-/- mice. In vivo
      administration of N-acetylcysteine (NAC) aggravated DSS-induced colitis and
      decreased Treg function to the level comparable to WT mice. Attenuated Th17 cell
      differentiation from naive CD4+ cells as well as impaired production of IL-6 and
      IL-17A by splenocytes upon stimulation suggested anti-inflammatory tendency of
      GPx1-/- * Cat-/- mice. Suppression of Stat3 activation in association with
      enhancement of indoleamine 2,3-dioxygenase and FoxP3 expression might be involved
      in the immunosuppressive mechanism of GPx1-/- * Cat-/- mice. Taken together, it
      is implied that ROS level is critical in the regulation of Treg function, and IBD
      may be attenuated in appropriately elevated levels of ROS.

PMID- 24743301
TI  - The effect of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) on semen
      parameters in human males: a systematic review and meta-analysis.
AB  - BACKGROUND: Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is one of
      the risk factors of impaired male fertility potential. Studies have investigated
      the effect of CP/CPPS on several semen parameters but have shown inconsistent
      results. Hence, we performed a systematic literature review and meta-analysis to
      assess the association between CP/CPPS and basic semen parameters in adult men.
      METHODS: Systematic literature searches were conducted with PubMed, EMBASE and
      the Cochrane Library up to August 2013 for case-control studies that involved the
      impact of CP/CPSS on semen parameters. Meta-analysis was performed with Review
      Manager and Stata software. Standard mean differences (SMD) of semen parameters
      were identified with 95% confidence intervals (95% CI) in a random effects model.
      RESULTS: Twelve studies were identified, including 999 cases of CP/CPPS and 455
      controls. Our results illustrated that the sperm concentration and the percentage
      of progressively motile sperm and morphologically normal sperm from patients with
      CP/CPPS were significantly lower than controls (SMD (95% CI) -14.12 (-21.69, 
      6.63), -5.94 (-8.63, -3.25) and -8.26 (-11.83, -4.66), respectively). However,
      semen volume in the CP/CPPS group was higher than in the control group (SMD (95%
      CI) 0.50 (0.11, 0.89)). There was no significant effect of CP/CPPS on the total
      sperm count, sperm total motility, and sperm vitality. CONCLUSIONS: The present
      study illustrates that there was a significant negative effect of CP/CPPS on
      sperm concentration, sperm progressive motility, and normal sperm morphology.
      Further studies with larger sample sizes are needed to better illuminate the
      negative impact of CP/CPPS on semen parameters.

PMID- 24743302
TI  - Experimental infection of rhesus macaques and common marmosets with a European
      strain of West Nile virus.
AB  - West Nile virus (WNV) is a mosquito-borne flavivirus that infects humans and
      other mammals. In some cases WNV causes severe neurological disease. During
      recent years, outbreaks of WNV are increasing in worldwide distribution and novel
      genetic variants of the virus have been detected. Although a substantial amount
      of data exists on WNV infections in rodent models, little is known about early
      events during WNV infection in primates, including humans. To gain a deeper
      understanding of this process, we performed experimental infections of rhesus
      macaques and common marmosets with a virulent European WNV strain (WNV-Ita09) and
      monitored virological, hematological, and biochemical parameters. WNV-Ita09
      productively infected both monkey species, with higher replication and wider
      tissue distribution in common marmosets compared to rhesus macaques. The animals
      in this study however, did not develop clinical signs of WNV disease, nor showed
      substantial deviations in clinical laboratory parameters. In both species, the
      virus induced a rapid CD56dimCD16bright natural killer response, followed by IgM
      and IgG antibody responses. The results of this study show that healthy rhesus
      macaques and common marmosets are promising animal models to study WNV-Ita09
      infection. Both models may be particularly of use to evaluate potential vaccine
      candidates or to investigate WNV pathogenesis. 

PMID- 24743303
TI  - Role of TNF in the altered interaction of dormant Mycobacterium tuberculosis with
      host macrophages.
AB  - Mycobacterium tuberculosis (Mtb) persists within lung granulomas, despite being
      subjected to diverse stress conditions, including hypoxia. We hypothesized that
      the response of host phagocytes to Mtb experiencing hypoxia is radically altered
      and designed in vitro experiment to study this phenomenon. Hypoxia-stressed (Mtb
      H) and aerobically grown Mtb (Mtb-A) were used to infect Rhesus Macaque Bone
      Marrow Derived Macrophages (Rh-BMDMs) and the comparative host response to Mtb
      infection studied. Mechanistic insights were gained by employing RNAi. Mtb-H
      accumulated significantly lower bacterial burden during growth in Rh-BMDMs,
      concomitantly generating a drastically different host transcriptional profile
      (with only <2% of all genes perturbed by either infection being shared between
      the two groups). A key component of this signature was significantly higher TNF
      and apopotosis in Mtb-H- compared to Mtb-A-infected Rh-BMDMs. Silencing of TNF by
      RNAi reversed the significant control of Mtb replication. These results indicate
      a potential mechanism for the rapid clearance of hypoxia-conditioned bacilli by
      phagocytes. In conclusion, hypoxia-conditioned Mtb undergo significantly
      different interactions with host macrophages compared to Mtb grown in normoxia.
      These interactions result in the induction of the TNF signaling pathway,
      activation of apoptosis, and DNA-damage stress response. Our results show that
      Mtb-H bacilli are particularly susceptible to killing governed by TNF. 

PMID- 24743306
TI  - Hedgehog: Multiple Paths for Multiple Roles in Shaping the Brain and Spinal Cord.
AB  - Since the discovery of the segment polarity gene Hedgehog in Drosophila three
      decades ago, our knowledge of Hedgehog signaling pathway has considerably
      improved and paved the way to a wide field of investigations in the developing
      and adult central nervous system. Its peculiar transduction mechanism together
      with its implication in tissue patterning, neural stem cell biology, and neural
      tissue homeostasis make Hedgehog pathway of interest in a high number of normal
      or pathological contexts. Consistent with its role during brain development,
      misregulation of Hedgehog signaling is associated with congenital diseases and
      tumorigenic processes while its recruitment in damaged neural tissue may be part
      of the repairing process. This review focuses on the most recent data regarding
      the Hedgehog pathway in the developing and adult central nervous system and also
      its relevance as a therapeutic target in brain and spinal cord diseases. 

PMID- 24743305
TI  - Interleukin-35 induces regulatory B cells that suppress autoimmune disease.
AB  - Interleukin-10 (IL-10)-producing regulatory B (Breg) cells suppress autoimmune
      disease, and increased numbers of Breg cells prevent host defense to infection
      and promote tumor growth and metastasis by converting resting CD4(+) T cells to
      regulatory T (Treg) cells. The mechanisms mediating the induction and development
      of Breg cells remain unclear. Here we show that IL-35 induces Breg cells and
      promotes their conversion to a Breg subset that produces IL-35 as well as IL-10.
      Treatment of mice with IL-35 conferred protection from experimental autoimmune
      uveitis (EAU), and mice lacking IL-35 (p35 knockout (KO) mice) or defective in IL
      35 signaling (IL-12Rbeta2 KO mice) produced less Breg cells endogenously or after
      treatment with IL-35 and developed severe uveitis. Adoptive transfer of Breg
      cells induced by recombinant IL-35 suppressed EAU when transferred to mice with
      established disease, inhibiting pathogenic T helper type 17 (TH17) and TH1 cells
      while promoting Treg cell expansion. In B cells, IL-35 activates STAT1 and STAT3
      through the IL-35 receptor comprising the IL-12Rbeta2 and IL-27Ralpha subunits.
      As IL-35 also induced the conversion of human B cells into Breg cells, these
      findings suggest that IL-35 may be used to induce autologous Breg and IL-35(+)
      Breg cells and treat autoimmune and inflammatory disease. 

PMID- 24743304
TI  - Soluble CEACAM8 interacts with CEACAM1 inhibiting TLR2-triggered immune
      responses.
AB  - Lower respiratory tract bacterial infections are characterized by neutrophilic
      inflammation in the airways. The carcinoembryonic antigen-related cell adhesion
      molecule (CEACAM) 8 is expressed in and released by human granulocytes. Our study
      demonstrates that human granulocytes release CEACAM8 in response to bacterial DNA
      in a TLR9-dependent manner. Individuals with a high percentage of bronchial
      lavage fluid (BALF) granulocytes were more likely to have detectable levels of
      released CEACAM8 in the BALF than those with a normal granulocyte count. Soluble,
      recombinant CEACAM8-Fc binds to CEACAM1 expressed on human airway epithelium.
      Application of CEACAM8-Fc to CEACAM1-positive human pulmonary epithelial cells
      resulted in reduced TLR2-dependent inflammatory responses. These inhibitory
      effects were accompanied by tyrosine phosphorylation of the immunoreceptor
      tyrosine-based inhibitory motif (ITIM) of CEACAM1 and by recruitment of the
      phosphatase SHP-1, which could negatively regulate Toll-like receptor 2-dependent
      activation of the phosphatidylinositol 3-OH kinase-Akt kinase pathway. Our
      results suggest a new mechanism by which granulocytes reduce pro-inflammatory
      immune responses in human airways via secretion of CEACAM8 in neutrophil-driven
      bacterial infections. 

PMID- 24743307
TI  - The sequence-specific transcription factor c-Jun targets Cockayne syndrome
      protein B to regulate transcription and chromatin structure.
AB  - Cockayne syndrome is an inherited premature aging disease associated with
      numerous developmental and neurological defects, and mutations in the gene
      encoding the CSB protein account for the majority of Cockayne syndrome cases.
      Accumulating evidence suggests that CSB functions in transcription regulation, in
      addition to its roles in DNA repair, and those defects in this transcriptional
      activity might contribute to the clinical features of Cockayne syndrome.
      Transcription profiling studies have so far uncovered CSB-dependent effects on
      gene expression; however, the direct targets of CSB's transcriptional activity
      remain largely unknown. In this paper, we report the first comprehensive analysis
      of CSB genomic occupancy during replicative cell growth. We found that CSB
      occupancy sites display a high correlation to regions with epigenetic features of
      promoters and enhancers. Furthermore, we found that CSB occupancy is enriched at
      sites containing the TPA-response element. Consistent with this binding site
      preference, we show that CSB and the transcription factor c-Jun can be found in
      the same protein-DNA complex, suggesting that c-Jun can target CSB to specific
      genomic regions. In support of this notion, we observed decreased CSB occupancy
      of TPA-response elements when c-Jun levels were diminished. By modulating CSB
      abundance, we found that CSB can influence the expression of nearby genes and
      impact nucleosome positioning in the vicinity of its binding site. These results
      indicate that CSB can be targeted to specific genomic loci by sequence-specific
      transcription factors to regulate transcription and local chromatin structure.
      Additionally, comparison of CSB occupancy sites with the MSigDB Pathways database
      suggests that CSB might function in peroxisome proliferation, EGF receptor
      transactivation, G protein signaling and NF-kappaB activation, shedding new light
      on the possible causes and mechanisms of Cockayne syndrome. 

PMID- 24743308
TI  - A toolbox for representational similarity analysis.
AB  - Neuronal population codes are increasingly being investigated with multivariate
      pattern-information analyses. A key challenge is to use measured brain-activity
      patterns to test computational models of brain information processing. One
      approach to this problem is representational similarity analysis (RSA), which
      characterizes a representation in a brain or computational model by the distance
      matrix of the response patterns elicited by a set of stimuli. The
      representational distance matrix encapsulates what distinctions between stimuli
      are emphasized and what distinctions are de-emphasized in the representation. A
      model is tested by comparing the representational distance matrix it predicts to
      that of a measured brain region. RSA also enables us to compare representations
      between stages of processing within a given brain or model, between brain and
      behavioral data, and between individuals and species. Here, we introduce a Matlab
      toolbox for RSA. The toolbox supports an analysis approach that is simultaneously
      data- and hypothesis-driven. It is designed to help integrate a wide range of
      computational models into the analysis of multichannel brain-activity
      measurements as provided by modern functional imaging and neuronal recording
      techniques. Tools for visualization and inference enable the user to relate sets
      of models to sets of brain regions and to statistically test and compare the
      models using nonparametric inference methods. The toolbox supports searchlight
      based RSA, to continuously map a measured brain volume in search of a neuronal
      population code with a specific geometry. Finally, we introduce the linear
      discriminant t value as a measure of representational discriminability that
      bridges the gap between linear decoding analyses and RSA. In order to demonstrate
      the capabilities of the toolbox, we apply it to both simulated and real fMRI
      data. The key functions are equally applicable to other modalities of brain
      activity measurement. The toolbox is freely available to the community under an
      open-source license agreement (http://www.mrc-cbu.cam.ac.uk/methods-and
      resources/toolboxes/license/). 

PMID- 24743309
TI  - Sweetened beverages, coffee, and tea and depression risk among older US adults.
AB  - Sweetened beverages, coffee, and tea are the most consumed non-alcoholic
      beverages and may have important health consequences. We prospectively evaluated
      the consumption of various types of beverages assessed in 1995-1996 in relation
      to self-reported depression diagnosis after 2000 among 263,923 participants of
      the NIH-AARP Diet and Health Study. Odds ratios (OR) and 95% confidence intervals
      (CI) were derived from multivariate logistic regressions. The OR (95% CI)
      comparing >=4 cans/cups per day with none were 1.30 (95%CI: 1.17-1.44) for soft
      drinks, 1.38 (1.15-1.65) for fruit drinks, and 0.91 (0.84-0.98) for coffee (all P
      for trend<0.0001). Null associations were observed for iced-tea and hot tea. In
      stratified analyses by drinkers of primarily diet versus regular beverages, the
      ORs were 1.31 (1.16-1.47) for diet versus 1.22 (1.03-1.45) for regular soft
      drinks, 1.51 (1.18-1.92) for diet versus 1.08 (0.79-1.46) for regular fruit
      drinks, and 1.25 (1.10-1.41) for diet versus 0.94 (0.83-1.08) for regular
      sweetened iced-tea. Finally, compared to nondrinkers, drinking coffee or tea
      without any sweetener was associated with a lower risk for depression, adding
      artificial sweeteners, but not sugar or honey, was associated with higher risks.
      Frequent consumption of sweetened beverages, especially diet drinks, may increase
      depression risk among older adults, whereas coffee consumption may lower the
      risk. 

PMID- 24743310
TI  - Expression of stanniocalcin-1 and stanniocalcin-2 in laryngeal squamous cell
      carcinoma and correlations with clinical and pathological parameters.
AB  - BACKGROUND: Stanniocalcin-1 (STC1) and stanniocalcin-2 (STC2) are secreted
      glycoprotein hormones involved in various types of human malignancies. The roles
      of STC1 and STC2 in laryngeal squamous cell carcinoma (LSCC) remain unknown. We
      investigated correlations between STC1 and STC2 expression and
      clinicopathological or prognostic factors in LSCC. METHODS: Pre-surgical
      peripheral blood samples were collected between 2012 and 2013 from 62 patients
      with LSCC. Quantitative RT-PCR analysis was performed to examine mRNA levels of
      STC1 and STC2. Immunohistochemistry was performed to retrospectively analyze 90
      paraffin-embedded LSCC tissue samples, which were obtained from patients who
      received surgery between 2006 and 2009. These patients did not have histories of
      treatment or malignancies. Univariate analysis of patient survival was performed
      by the Kaplan-Meier method. Multivariate analyses were performed with the Cox
      proportional hazards model. RESULTS: The relative mRNA levels of STC1 and STC2 in
      peripheral blood were significantly greater in LSCC patients than those of
      healthy volunteers (both P<0.05). STC2 protein expression in tumor tissues was
      associated with invasion into the thyroid cartilage, T-Stage, lymphatic
      metastasis, clinical stage, and pathological differentiation (all P<0.05). In
      addition, STC2 protein expression was an independent prognostic factor for
      overall survival in patients with LSCC (P = 0.025). In contrast, STC1 expression
      only correlated with clinical stage (P = 0.026) and was not an independent or
      significant prognostic factor. CONCLUSIONS: Circulating STC1 and STC2 mRNA are
      potentially useful blood markers for LSCC. Our results strongly suggest that the
      STC2 protein, but not STC1, may be a valuable biomarker for LSCC malignancies and
      a prognostic marker for poor outcome following surgery. Future studies should
      examine STC2 as a novel molecular target for the treatment of LSCC.

PMID- 24743311
TI  - Construction of a highly active xylanase displaying oleaginous yeast: comparison
      of anchoring systems.
AB  - Three Yarrowia lipolytica cell wall proteins (YlPir, YlCWP1 and YlCBM) were
      evaluated for their ability to display the xylanase TxXYN from Thermobacillus
      xylanilyticus on the cell surface of Y. lipolytica. The fusion proteins were
      produced in Y. lipolytica JMY1212, a strain engineered for mono-copy chromosomal
      insertion, and enabling accurate comparison of anchoring systems. The
      construction using YlPir enabled cell bound xylanase activity to be maximised
      (71.6 U/g). Although 48% of the activity was released in the supernatant,
      probably due to proteolysis at the fusion zone, this system is three times more
      efficient for the anchoring of TxXYN than the YlCWP1 system formerly developed
      for Y. lipolytica. As far as we know it represents the best displayed xylanase
      activity ever published. It could be an attractive alternative anchoring system
      to display enzymes in Y. lipolytica. 

PMID- 24743312
TI  - In others' shoes: do individual differences in empathy and theory of mind shape
      social preferences?
AB  - Abundant evidence across the behavioral and social sciences suggests that there
      are substantial individual differences in pro-social behavior. However, little is
      known about the psychological mechanisms that underlie social preferences. This
      paper investigates whether empathy and Theory of Mind shape individual
      differences in pro-social behavior as conventionally observed in neutrally framed
      social science experiments. Our results show that individual differences in the
      capacity for empathy do not shape social preferences. The results qualify the
      role of Theory of Mind in strategic interaction. We do not only show that fair
      individuals exhibit more accurate beliefs about the behavior of others but that
      Theory of Mind can be effectively used to pursue both self-interest and pro
      social goals depending on the principle objectives of a person. 

PMID- 24743313
TI  - Relevance of early poststress variation in left ventricular function studied by
      gated-SPECT: evaluation in different clinical settings and relationship with
      angiography results.
AB  - BACKGROUND: Stress-induced ischemia may cause a decrease in left ventricular
      ejection fraction (EF). We evaluated the variation in early postexercise EF (S
      EF) compared with rest EF (R-EF) in different clinical settings to detect
      ventricular dysfunction. We also correlated ventricular dysfunction with an
      angiographic score, the Syntax score, in a subgroup of ischemic patients.
      MATERIALS AND METHODS: Gated-SPECT images were acquired 12 min after exercise
      stress and at rest in 1481 patients. Patients were classified as controls,
      negative for ischemia, mildly ischemic, moderately/severely ischemic, necrotic,
      and necrotic with ischemia. Mean end-diastolic volume, end-systolic volume, and
      EF were compared in each group. The ratio between stress to rest EF was indicated
      as the functional score. Angiography results were collected for 55% of
      moderately/severely ischemic patients. Sixty-one angiographies were also
      completed with Syntax score evaluation. RESULTS: In negative, necrotic, and
      mildly ischemic patients no differences were found between S-EF and R-EF. An
      opposite trend was observed in moderately/severely ischemic patients with a
      decrement of S-EF compared with R-EF (54.80+/-11.33 vs. 57.79+/-11.14; P<0.0001).
      Coronary artery disease was confirmed by angiography in 93% of
      moderately/severely ischemic patients. In 61 patients who underwent Syntax score
      evaluation, significant correlation was observed with functional score.
      Significant decrease in functional score was found in patients with coronary
      artery bypass graft indication compared with patients with percutaneous coronary
      intervention or medical indication. CONCLUSION: Early poststress gated-SPECT
      acquisition allows the detection of ventricular dysfunction in
      moderately/severely ischemic disease and provides additional information when
      directing patients to angiography and revascularization.

PMID- 24743314
TI  - Detection of pulmonary embolism during pregnancy: comparing radiation doses of
      CTPA and pulmonary scintigraphy.
AB  - OBJECTIVE: In pregnant patients pulmonary embolism is a common occurrence with
      potentially devastating outcomes, necessitating timely imaging diagnosis. In
      every patient, especially in pregnant patients, radiation exposure is an
      important consideration while selecting the best imaging modality. MATERIALS AND
      METHODS: We performed a retrospective analysis comparing radiation doses of
      computed tomography pulmonary angiography (CTPA), perfusion scintigraphy, and
      perfusion/ventilation scintigraphy for suspected pulmonary embolism in 53
      pregnant patients at our hospital between 2006 and 2012. Effective dose and
      breast-absorbed and uterus-absorbed doses for CTPA as well as effective dose and
      breast and fetus-absorbed doses for pulmonary scintigraphy were estimated using
      International Commission on Radiological Protection 103 weighting factors.
      RESULTS: For CTPA and perfusion scintigraphy, average doses were estimated as
      effective doses of 21 and 1.04 mSv, breast-absorbed doses of 44 and 0.28 mGy, and
      uterus-absorbed dose of 0.46 mGy and fetal-absorbed dose of 0.25 mGy,
      respectively. With inclusion of the ventilation component of pulmonary
      scintigraphy, doses increased to an effective dose of 1.29 mSv, a breast-absorbed
      dose of 0.37 mGy, and a fetal-absorbed dose of 0.40 mGy. CONCLUSION: Perfusion
      nuclear medicine study has a statistically significantly lower effective and
      breast-absorbed dose (P<0.0001) when compared with CTPA. Similarly, the fetal
      absorbed dose for pulmonary scintigraphy has a statistically lower dose
      (P=0.0010) when compared with CTPA, even if the ventilation component of
      pulmonary scintigraphy is performed, although these values are so small that they
      are unlikely to be clinically significant.

PMID- 24743315
TI  - Effects of local tree diversity on herbivore communities diminish with increasing
      forest fragmentation on the landscape scale.
AB  - Forest fragmentation and plant diversity have been shown to play a crucial role
      for herbivorous insects (herbivores, hereafter). In turn, herbivory-induced leaf
      area loss is known to have direct implications for plant growth and reproduction
      as well as long-term consequences for ecosystem functioning and forest
      regeneration. So far, previous studies determined diverging responses of
      herbivores to forest fragmentation and plant diversity. Those inconsistent
      results may be owed to complex interactive effects of both co-occurring
      environmental factors albeit they act on different spatial scales. In this study,
      we investigated whether forest fragmentation on the landscape scale and tree
      diversity on the local habitat scale show interactive effects on the herbivore
      community and leaf area loss in subtropical forests in South Africa. We applied
      standardized beating samples and a community-based approach to estimate changes
      in herbivore community composition, herbivore abundance, and the effective number
      of herbivore species on the tree species-level. We further monitored leaf area
      loss to link changes in the herbivore community to the associated process of
      herbivory. Forest fragmentation and tree diversity interactively affected the
      herbivore community composition, mainly by a species turnover within the family
      of Curculionidae. Furthermore, herbivore abundance increased and the number of
      herbivore species decreased with increasing tree diversity in slightly fragmented
      forests whereas the effects diminished with increasing forest fragmentation.
      Surprisingly, leaf area loss was neither affected by forest fragmentation or tree
      diversity, nor by changes in the herbivore community. Our study highlights the
      need to consider interactive effects of environmental changes across spatial
      scales in order to draw reliable conclusions for community and interaction
      patterns. Moreover, forest fragmentation seems to alter the effect of tree
      diversity on the herbivore community, and thus, has the potential to jeopardize
      ecosystem functioning and forest regeneration. 

PMID- 24743316
TI  - Imiquimod induces apoptosis of squamous cell carcinoma (SCC) cells via regulation
      of A20.
AB  - Imiquimod, a nucleoside analogue of the imidazoquinoline family, is being used to
      treat various cutaneous cancers including squamous cell carcinoma (SCC).
      Imiquimod activates anti-tumor immunity via Toll-like receptor 7 (TLR7) in
      macrophage and other immune cells. Imiquimod can also affect tumor cells
      directly, regardless of its impact on immune system. In this study, we
      demonstrated that imiquimod induced apoptosis of SCC cells (SCC12) and A20 was
      involved in this process. When A20 was overexpressed, imiquimod-induced apoptosis
      was markedly inhibited. Conversely, knockdown of A20 potentiated imiquimod
      induced apoptosis. Interestingly, A20 counteracted activation of c-Jun N-terminal
      kinase (JNK), suggesting that A20-regulated JNK activity was possible mechanism
      underlying imiquimod-induced apoptosis of SCC12 cells. Finally, imiquimod-induced
      apoptosis of SCC12 cells was taken place in a TLR7-independent manner. Our data
      provide new insight into the mechanism underlying imiquimod effect in cutaneous
      cancer treatment.

PMID- 24743317
TI  - Centrosomes at M phase act as a scaffold for the accumulation of intracellular
      ubiquitinated proteins.
AB  - Centrosome size varies considerably during the cell cycle; it is greatest during
      metaphase, partly because of pericentriolar matrix recruitment and an increase in
      microtubule-organizing activity. However, the mechanism of centrosome maturation
      during M phase is poorly defined. In the present study, we identified and
      quantified centrosomal proteins during S and M phases using stable isotope
      labeling by amino acids in cell culture (SILAC) coupled with liquid
      chromatography-tandem mass spectrometry (LC-MS/MS). We identified 991 proteins,
      of which 310 and 325 proteins were upregulated during S and M phases,
      respectively. Ubiquitinated proteins containing K48- and K63-linked polyubiquitin
      chains accumulated in the centrosomes during M phase, although 26S proteasome
      activity in the centrosomes did not markedly differ between S and M phases.
      Conversely, cytoplasmic dynein, which transports ubiquitinated proteins to the
      centrosomes, increased 2-fold in the centrosomes during M phase relative to S
      phase. Furthermore, PYR-41, a ubiquitin E1 inhibitor, reduced centrosome size
      during metaphase, causing increased aneuploidy. RNA interference suppression of
      Ecm29, which inhibits proteasome activity, decreased the accumulation of
      ubiquitinated proteins in the centrosomes. These results show that accumulation
      of ubiquitinated proteins promotes centrosome maturation during M phase and
      further suggest a novel function of centrosomes as a scaffold temporarily
      gathering intracellular ubiquitinated proteins. 

PMID- 24743319
TI  - Efficient generation of myostatin (MSTN) biallelic mutations in cattle using zinc
      finger nucleases.
AB  - Genetically engineered zinc-finger nucleases (ZFNs) are useful for marker-free
      gene targeting using a one-step approach. We used ZFNs to efficiently disrupt
      bovine myostatin (MSTN), which was identified previously as the gene responsible
      for double muscling in cattle. The mutation efficiency of bovine somatic cells
      was approximately 20%, and the biallelic mutation efficiency was 8.3%. To
      evaluate the function of the mutated MSTN locus before somatic cell nuclear
      transfer, MSTN mRNA and protein expression was examined in four mutant cell
      colonies. We generated marker-gene-free cloned cattle, in which the MSTN
      biallelic mutations consisted of a 6-bp deletion in one of the alleles and a 117
      bp deletion and 9-bp insertion in the other allele, resulting in at least four
      distinct mRNA splice variants. In the MSTN mutant cattle, the total amount of
      MSTN protein with the C-terminal domain was reduced by approximately 50%, and
      hypertrophied muscle fibers of the quadriceps and the double-muscled phenotype
      appeared at one month of age. Our proof-of-concept study is the first to produce
      MSTN mutations in cattle, and may allow the development of genetically modified
      strains of double-muscled cattle. 

PMID- 24743320
TI  - Patterns of DNA barcode variation in Canadian marine molluscs.
AB  - BACKGROUND: Molluscs are the most diverse marine phylum and this high diversity
      has resulted in considerable taxonomic problems. Because the number of species in
      Canadian oceans remains uncertain, there is a need to incorporate molecular
      methods into species identifications. A 648 base pair segment of the cytochrome c
      oxidase subunit I gene has proven useful for the identification and discovery of
      species in many animal lineages. While the utility of DNA barcoding in molluscs
      has been demonstrated in other studies, this is the first effort to construct a
      DNA barcode registry for marine molluscs across such a large geographic area.
      METHODOLOGY/PRINCIPAL FINDINGS: This study examines patterns of DNA barcode
      variation in 227 species of Canadian marine molluscs. Intraspecific sequence
      divergences ranged from 0-26.4% and a barcode gap existed for most taxa. Eleven
      cases of relatively deep (>2%) intraspecific divergence were detected, suggesting
      the possible presence of overlooked species. Structural variation was detected in
      COI with indels found in 37 species, mostly bivalves. Some indels were present in
      divergent lineages, primarily in the region of the first external loop,
      suggesting certain areas are hotspots for change. Lastly, mean GC content varied
      substantially among orders (24.5%-46.5%), and showed a significant positive
      correlation with nearest neighbour distances. CONCLUSIONS/SIGNIFICANCE: DNA
      barcoding is an effective tool for the identification of Canadian marine molluscs
      and for revealing possible cases of overlooked species. Some species with deep
      intraspecific divergence showed a biogeographic partition between lineages on the
      Atlantic, Arctic and Pacific coasts, suggesting the role of Pleistocene
      glaciations in the subdivision of their populations. Indels were prevalent in the
      barcode region of the COI gene in bivalves and gastropods. This study highlights
      the efficacy of DNA barcoding for providing insights into sequence variation
      across a broad taxonomic group on a large geographic scale.

PMID- 24743321
TI  - Inhibitory control in bilinguals and musicians: event related potential (ERP)
      evidence for experience-specific effects.
AB  - Bilinguals and musicians exhibit behavioral advantages on tasks with high demands
      on executive functioning, particularly inhibitory control, but the brain
      mechanisms supporting these differences are unclear. Of key interest is whether
      these forms of experience influence cognition through similar or distinct
      information processing mechanisms. Here, we recorded event-related potentials
      (ERPs) in three groups - bilinguals, musicians, and controls - who completed a
      visual go-nogo task that involved the withholding of key presses to rare targets.
      Participants in each group achieved similar accuracy rates and responses times
      but the analysis of cortical responses revealed significant differences in ERP
      waveforms. Success in withholding a prepotent response was associated with
      enhanced stimulus-locked N2 and P3 wave amplitude relative to go trials. For nogo
      trials, there were altered timing-specific ERP differences and graded amplitude
      differences observed in the neural responses across groups. Specifically,
      musicians showed an enhanced early P2 response accompanied by reduced N2
      amplitude whereas bilinguals showed increased N2 amplitude coupled with an
      increased late positivity wave relative to controls. These findings demonstrate
      that bilingualism and music training have differential effects on the brain
      networks supporting executive control over behavior. 

PMID- 24743322
TI  - El Nino Southern Oscillation and leptospirosis outbreaks in New Caledonia.
AB  - Leptospirosis is an important cause of seasonal outbreaks in New Caledonia and
      the tropics. Using time series derived from high-quality laboratory-based
      surveillance from 2000-2012, we evaluated whether climatic factors, including El
      Nino Southern Oscillation (ENSO) and meteorological conditions allow for the
      prediction of leptospirosis outbreaks in New Caledonia. We found that La Nina
      periods are associated with high rainfall, and both of these factors were in
      turn, temporally associated with outbreaks of leptospirosis. The sea surface
      temperature in El Nino Box 4 allowed forecasting of leptospirosis outbreaks four
      months into the future, a time lag allowing public health authorities to increase
      preparedness. To our knowledge, our observations in New Caledonia are the first
      demonstration that ENSO has a strong association with leptospirosis. This
      association should be tested in other regions in the South Pacific, Asia or Latin
      America where ENSO may drive climate variability and the risk for leptospirosis
      outbreaks. 

PMID- 24743324
TI  - Avalanches in self-organized critical neural networks: a minimal model for the
      neural SOC universality class.
AB  - The brain keeps its overall dynamics in a corridor of intermediate activity and
      it has been a long standing question what possible mechanism could achieve this
      task. Mechanisms from the field of statistical physics have long been suggesting
      that this homeostasis of brain activity could occur even without a central
      regulator, via self-organization on the level of neurons and their interactions,
      alone. Such physical mechanisms from the class of self-organized criticality
      exhibit characteristic dynamical signatures, similar to seismic activity related
      to earthquakes. Measurements of cortex rest activity showed first signs of
      dynamical signatures potentially pointing to self-organized critical dynamics in
      the brain. Indeed, recent more accurate measurements allowed for a detailed
      comparison with scaling theory of non-equilibrium critical phenomena, proving the
      existence of criticality in cortex dynamics. We here compare this new evaluation
      of cortex activity data to the predictions of the earliest physics spin model of
      self-organized critical neural networks. We find that the model matches with the
      recent experimental data and its interpretation in terms of dynamical signatures
      for criticality in the brain. The combination of signatures for criticality,
      power law distributions of avalanche sizes and durations, as well as a specific
      scaling relationship between anomalous exponents, defines a universality class
      characteristic of the particular critical phenomenon observed in the neural
      experiments. Thus the model is a candidate for a minimal model of a self
      organized critical adaptive network for the universality class of neural
      criticality. As a prototype model, it provides the background for models that may
      include more biological details, yet share the same universality class
      characteristic of the homeostasis of activity in the brain. 

PMID- 24743325
TI  - Comparing forests across climates and biomes: qualitative assessments, reference
      forests and regional intercomparisons.
AB  - Communities, policy actors and conservationists benefit from understanding what
      institutions and land management regimes promote ecosystem services like carbon
      sequestration and biodiversity conservation. However, the definition of success
      depends on local conditions. Forests' potential carbon stock, biodiversity and
      rate of recovery following disturbance are known to vary with a broad suite of
      factors including temperature, precipitation, seasonality, species' traits and
      land use history. Methods like tracking over-time changes within forests, or
      comparison with "pristine" reference forests have been proposed as means to
      compare the structure and biodiversity of forests in the face of underlying
      differences. However, data from previous visits or reference forests may be
      unavailable or costly to obtain. Here, we introduce a new metric of locally
      weighted forest intercomparison to mitigate the above shortcomings. This method
      is applied to an international database of nearly 300 community forests and
      compared with previously published techniques. It is particularly suited to large
      databases where forests may be compared among one another. Further, it avoids
      problematic comparisons with old-growth forests which may not resemble the goal
      of forest management. In most cases, the different methods produce broadly
      congruent results, suggesting that researchers have the flexibility to compare
      forest conditions using whatever type of data is available. Forest structure and
      biodiversity are shown to be independently measurable axes of forest condition,
      although users' and foresters' estimations of seemingly unrelated attributes are
      highly correlated, perhaps reflecting an underlying sentiment about forest
      condition. These findings contribute new tools for large-scale analysis of
      ecosystem condition and natural resource policy assessment. Although applied here
      to forestry, these techniques have broader applications to classification and
      evaluation problems using crowdsourced or repurposed data for which baselines or
      external validations are not available. 

PMID- 24743326
TI  - Self-management behavior in patients with type 2 diabetes: a cross-sectional
      survey in western urban China.
AB  - PURPOSE: To investigate the current status of diabetic self-management behavior
      and the factors influencing this behavior in Chengdu, a typical city in western
      China. METHODS: We performed stratified sampling in 6 urban districts of Chengdu.
      We used questionnaires concerning self-management knowledge, self-management
      beliefs, self-management efficacy, social support, and self-management behavior
      to investigate patients with T2DM from August to November 2011. All of the data
      were analyzed using the SPSS 17.0 statistical package. RESULTS: We enrolled a
      total of 364 patients in the present study. The median score of self-management
      behavior was 111.00, the interquartile range was 100.00-119.00, and the index
      score was 77.77. Self-management was described as "good" in 46%, "fair" in 45%,
      and "poor" in 6% of patients. A multiple-factor analysis identified age (OR,
      0.43; 95% CI, 0.20-0.91; P = 0.026), education in "foot care" (OR, 0.42; 95% CI,
      0.18-0.99; P = 0.048), self-management knowledge (OR, 0.86; 95% CI, 0.80-0.92;
      P<0.001), self-management belief (OR, 0.92; 95% CI, 0.87-0.97; P = 0.002), self
      efficacy (OR, 0.93; 95% CI, 0.90-0.96; P<0.001), and social support (OR, 0.62;
      95% CI, 0.41-0.94; P = 0.023) as positive factors. Negative factors included
      diabetes duration (5-9 years: OR, 14.82; 95% CI, 1.64-133.73; P = 0.016; and >=10
      years: OR, 10.28; 95% CI, 1.06-99.79; P = 0.045) and hospitalization experience
      (OR, 2.96; 95% CI, 1.64-5.36; P<0.001). CONCLUSION: We observed good self
      management behavior in patients with T2DM in Chengdu. When self-management
      education is provided, age, education, knowledge, belief, self-efficacy, and
      social support should be considered to offer more appropriate intervention and to
      improve patients' behavior.

PMID- 24743328
TI  - Knowledge, attitudes and practices related to visceral leishmaniasis in rural
      communities of Amhara State: a longitudinal study in northwest Ethiopia.
AB  - BACKGROUND: In the northwest of Ethiopia, at the South Gondar region, there was a
      visceral leishmaniasis (VL) outbreak in 2005, making the disease a public health
      concern for the regional health authorities ever since. The knowledge on how the
      population perceives the disease is essential in order to propose successful
      control strategies. METHODOLOGY/PRINCIPAL FINDINGS: Two surveys on VL knowledge,
      attitudes and practices were conducted at the beginning (May 2009) and at the end
      (February 2011) of a VL longitudinal study carried out in rural communities of
      Libo Kemkem and Fogera, two districts of the Amhara Regional State. Results
      showed that VL global knowledge was very low in the area, and that it improved
      substantially in the period studied. Specifically, from 2009 to 2011, the
      frequency of proper knowledge regarding VL signs and symptoms increased from 47%
      to 71% (p<0.0001), knowledge of VL causes increased from 8% to 25% (p<0.0001),
      and knowledge on VL protection measures from 16% to 55% (p<0.0001). Moreover, the
      improvement observed in VL knowledge was more marked among the families with no
      previous history of VL case. Finally, in 2011 more than 90% of the households
      owned at least an impregnated bed net and had been sprayed, and attitudes towards
      these and other protective measures were very positive (over 94% acceptance for
      all of them). CONCLUSIONS/SIGNIFICANCE: In 2009 the level of knowledge regarding
      VL was very low among the rural population of this area, although it improved
      substantially in the study period, probably due to the contribution of many
      actors in the area. VL patients and relatives should be appropriately informed
      and trained as they may act as successful health community agents. VL risk
      behavioural patterns are subject to change as attitudes towards protective
      measures were very positive overall.

PMID- 24743329
TI  - FANSe2: a robust and cost-efficient alignment tool for quantitative next
      generation sequencing applications.
AB  - Correct and bias-free interpretation of the deep sequencing data is inevitably
      dependent on the complete mapping of all mappable reads to the reference
      sequence, especially for quantitative RNA-seq applications. Seed-based algorithms
      are generally slow but robust, while Burrows-Wheeler Transform (BWT) based
      algorithms are fast but less robust. To have both advantages, we developed an
      algorithm FANSe2 with iterative mapping strategy based on the statistics of real
      world sequencing error distribution to substantially accelerate the mapping
      without compromising the accuracy. Its sensitivity and accuracy are higher than
      the BWT-based algorithms in the tests using both prokaryotic and eukaryotic
      sequencing datasets. The gene identification results of FANSe2 is experimentally
      validated, while the previous algorithms have false positives and false
      negatives. FANSe2 showed remarkably better consistency to the microarray than
      most other algorithms in terms of gene expression quantifications. We implemented
      a scalable and almost maintenance-free parallelization method that can utilize
      the computational power of multiple office computers, a novel feature not present
      in any other mainstream algorithm. With three normal office computers, we
      demonstrated that FANSe2 mapped an RNA-seq dataset generated from an entire
      Illunima HiSeq 2000 flowcell (8 lanes, 608 M reads) to masked human genome within
      4.1 hours with higher sensitivity than Bowtie/Bowtie2. FANSe2 thus provides
      robust accuracy, full indel sensitivity, fast speed, versatile compatibility and
      economical computational utilization, making it a useful and practical tool for
      deep sequencing applications. FANSe2 is freely available at
      http://bioinformatics.jnu.edu.cn/software/fanse2/. 

PMID- 24743330
TI  - Serum proteomic analysis reveals high frequency of haptoglobin deficiency and
      elevated thyroxine level in heroin addicts.
AB  - Heroin addiction is a chronic, complex disease, often accompanied by other
      concomitant disorders, which may encumber effective prevention and treatment. To
      explore the differences in expression profiles of serum proteins in control and
      heroin addicts, we used two-dimensional electrophoresis coupled to MALDI-TOF/TOF,
      and identified 4 proteins of interest. Following validation of the increase in
      serum transthyretin, we assessed serum levels of thyroid stimulating hormone
      (TSH), triiodothyronine (T3), and thyroxine (T4), and observed a robust increase
      in T4 in heroin addicts compared to controls. In addition, we performed
      haptoglobin (Hp) phenotyping, and showed that the frequency of Hp0 (serum devoid
      of haptoglobin) was significantly higher in heroin addicts. Altogether, these
      findings indicated that: (1) thyroid hormone imbalance is present in heroin
      addicts; (2) anhaptoglobinemia (Hp0) might a risk factor or a deleterious effect
      of heroin abuse.

PMID- 24743323
TI  - Genetic predisposition to in situ and invasive lobular carcinoma of the breast.
AB  - Invasive lobular breast cancer (ILC) accounts for 10-15% of all invasive breast
      carcinomas. It is generally ER positive (ER+) and often associated with lobular
      carcinoma in situ (LCIS). Genome-wide association studies have identified more
      than 70 common polymorphisms that predispose to breast cancer, but these studies
      included predominantly ductal (IDC) carcinomas. To identify novel common
      polymorphisms that predispose to ILC and LCIS, we pooled data from 6,023 cases
      (5,622 ILC, 401 pure LCIS) and 34,271 controls from 36 studies genotyped using
      the iCOGS chip. Six novel SNPs most strongly associated with ILC/LCIS in the
      pooled analysis were genotyped in a further 516 lobular cases (482 ILC, 36 LCIS)
      and 1,467 controls. These analyses identified a lobular-specific SNP at 7q34
      (rs11977670, OR (95%CI) for ILC = 1.13 (1.09-1.18), P = 6.0 * 10(-10); P-het for
      ILC vs IDC ER+ tumors = 1.8 * 10(-4)). Of the 75 known breast cancer
      polymorphisms that were genotyped, 56 were associated with ILC and 15 with LCIS
      at P<0.05. Two SNPs showed significantly stronger associations for ILC than LCIS
      (rs2981579/10q26/FGFR2, P-het = 0.04 and rs889312/5q11/MAP3K1, P-het = 0.03); and
      two showed stronger associations for LCIS than ILC (rs6678914/1q32/LGR6, P-het =
      0.001 and rs1752911/6q14, P-het = 0.04). In addition, seven of the 75 known loci
      showed significant differences between ER+ tumors with IDC and ILC histology,
      three of these showing stronger associations for ILC (rs11249433/1p11,
      rs2981579/10q26/FGFR2 and rs10995190/10q21/ZNF365) and four associated only with
      IDC (5p12/rs10941679; rs2588809/14q24/RAD51L1, rs6472903/8q21 and
      rs1550623/2q31/CDCA7). In conclusion, we have identified one novel lobular breast
      cancer specific predisposition polymorphism at 7q34, and shown for the first time
      that common breast cancer polymorphisms predispose to LCIS. We have shown that
      many of the ER+ breast cancer predisposition loci also predispose to ILC,
      although there is some heterogeneity between ER+ lobular and ER+ IDC tumors.
      These data provide evidence for overlapping, but distinct etiological pathways
      within ER+ breast cancer between morphological subtypes.

PMID- 24743331
TI  - Enhanced methods for local ancestry assignment in sequenced admixed individuals.
AB  - Inferring the ancestry at each locus in the genome of recently admixed
      individuals (e.g., Latino Americans) plays a major role in medical and population
      genetic inferences, ranging from finding disease-risk loci, to inferring
      recombination rates, to mapping missing contigs in the human genome. Although
      many methods for local ancestry inference have been proposed, most are designed
      for use with genotyping arrays and fail to make use of the full spectrum of data
      available from sequencing. In addition, current haplotype-based approaches are
      very computationally demanding, requiring large computational time for moderately
      large sample sizes. Here we present new methods for local ancestry inference that
      leverage continent-specific variants (CSVs) to attain increased performance over
      existing approaches in sequenced admixed genomes. A key feature of our approach
      is that it incorporates the admixed genomes themselves jointly with public
      datasets, such as 1000 Genomes, to improve the accuracy of CSV calling. We use
      simulations to show that our approach attains accuracy similar to widely used
      computationally intensive haplotype-based approaches with large decreases in
      runtime. Most importantly, we show that our method recovers comparable local
      ancestries, as the 1000 Genomes consensus local ancestry calls in the real
      admixed individuals from the 1000 Genomes Project. We extend our approach to
      account for low-coverage sequencing and show that accurate local ancestry
      inference can be attained at low sequencing coverage. Finally, we generalize CSVs
      to sub-continental population-specific variants (sCSVs) and show that in some
      cases it is possible to determine the sub-continental ancestry for short
      chromosomal segments on the basis of sCSVs. 

PMID- 24743332
TI  - Increased microRNA-155 and decreased microRNA-146a may promote ocular
      inflammation and proliferation in Graves' ophthalmopathy.
AB  - Graves' ophthalmopathy is an inflammatory autoimmune disease of the orbit,
      characterized by inflammation and proliferation of the orbital tissue caused by
      CD4+T cells and orbital fibroblasts. Despite recent substantial findings
      regarding its cellular and molecular foundations, the pathogenesis of Graves'
      ophthalmopathy remains unclear. Accumulating data suggest that microRNAs play
      important roles in the pathophysiology of autoimmunity and proliferation.
      Specifically, microRNA-155 (miR-155) can promote autoimmune inflammation by
      enhancing inflammatory T cell development. In contrast to miR-155, microRNA-146a
      (miR-146a) can inhibit the immune response by suppressing T cell activation.
      Furthermore, miR-155 and miR-146a are involved in cell proliferation,
      differentiation, and many other life processes. Thus, miR-155 and miR-146a, with
      opposite impacts on inflammatory responses carried out by T lymphocytes, appear
      to have multiple targets in the pathogenesis of Graves' ophthalmopathy. Our
      previous work showed that the expression of miR-146a was significantly decreased
      in peripheral blood mononuclear cells from Graves' ophthalmopathy patients
      compared with normal subjects. Accordingly, we proposed that the expression of
      miR-155 increased and the expression of miR-146a decreased in the target cells
      (CD4+T cells and orbital fibroblasts), thus promoting ocular inflammation and
      proliferation in Graves' ophthalmopathy. The proposed hypothesis warrants further
      investigation of the function of the differentially expressed microRNAs, which
      may shed new light on the pathogenesis of Graves' ophthalmopathy and lead to new
      strategies for its management.

PMID- 24743333
TI  - The limit of detection in scintigraphic imaging with I-131 in patients with
      differentiated thyroid carcinoma.
AB  - Radioiodine scintigraphy influences staging and treatment in patients with
      differentiated thyroid carcinoma. The limit of detection for fractional uptake in
      an iodine avid focus in a scintigraphic image was determined from the number of
      lesion net counts and the count density of the tissue background. The count
      statistics were used to calculate the diagnostic activity required to elevate the
      signal from a lesion with a given uptake significantly above a homogeneous
      background with randomly distributed counts per area. The dependences of the
      minimal uptake and the minimal size of lesions visible in a scan on several
      parameters of influence were determined by linking the typical biokinetics
      observed in iodine avid tissue to the lesion mass and to the absorbed dose
      received in a radioiodine therapy. The detection limits for fractional uptake in
      a neck lesion of a typical patient are about 0.001% after therapy with 7000 MBq,
      0.01% for activities typically administered in diagnostic assessments (74-185
      MBq), and 0.1% after the administration of 10 MBq I-131. Lesions at the limit of
      detection in a diagnostic scan with biokinetics eligible for radioiodine therapy
      are small with diameters of a few millimeters. Increasing the diagnostic activity
      by a factor of 4 reduces the diameter of visible lesions by 25% or about 1 mm.
      Several other determinants have a comparable or higher influence on the limit of
      detection than the administered activity; most important are the biokinetics in
      both blood pool and target tissue and the time of measurement. A generally valid
      recommendation for the timing of the scan is impossible as the time of the
      highest probability to detect iodine avid tissue depends on the administered
      activity as well as on the biokinetics in the lesion and background in the
      individual patient. 

PMID- 24743334
TI  - Intention to switch to smokeless tobacco use among South African smokers: results
      from the 2007 South African Social Attitudes Survey.
AB  - BACKGROUND: Some smokeless tobacco products (SLT) have been shown to be
      associated with only a fraction of the risks of cigarettes. This study assessed
      South African smokers' interest in switching to a hypothetical reduced harm SLT
      product. METHODS: The 2007 South African Social Attitudes Survey was analysed for
      678 exclusive cigarette smokers. Respondents were asked about their perceptions
      about relative harm of snuff compared to cigarettes, and their interest in
      switching to snuff if informed it was 99% less harmful than cigarettes. RESULTS:
      About 49.7% of exclusive cigarette smokers believed that snuff was equally as
      harmful as cigarettes; 12.9% thought snuff was more harmful; 5.7% thought snuff
      was less harmful; while 31.8% did not know if there was a difference in harm
      between snuff and cigarettes. Approximately 24.2% of exclusive cigarette smokers
      indicated interest in switching to snuff, with significantly greater interest
      observed among those exposed to 100% smoke-free work environment. Interest in
      switching was highest (34.7%) among smokers who believed a priori that using
      snuff was more harmful than cigarettes, and lowest (14.5%) among those who did
      not know if there was a difference in harm. In a multi-variable adjusted logistic
      regression model, this latter group remained less likely to be interested in harm
      reduction switching (adjusted odds ratio = 0.42; 95% CI: 0.19-0.91). CONCLUSION:
      About a quarter of smokers indicated interest in harm reduction switching to
      snuff. SLT products have a potential role in reducing the harm from smoking in
      South Africa, but only if they are not used to circumvent smoke-free laws that
      have been associated with reduced smoking.

PMID- 24743335
TI  - Intratumoral CD8+ cytotoxic lymphocyte is a favorable prognostic marker in node
      negative breast cancer.
AB  - BACKGROUND: The prognostic effect of tumor infiltrating CD8+ cytotoxic
      lymphocytes (CTLs) in breast cancer is controversial. We analyzed the association
      between CD8+ CTLs and survival of untreated node-negative breast cancer patients.
      MATERIAL AND METHODS: CD8+ CTLs infiltrate was evaluated by immunostaining in a
      cohort of 332 node-negative breast cancer patients with a median follow-up of 152
      months. The prognostic significance of CD8+ CTLs for disease-free survival (DFS)
      and breast cancer-specific overall survival (OS) was evaluated with Kaplan-Meier
      survival analysis as well as univariate analysis and multivariate Cox analysis
      adjusted for age at diagnosis, pT stage, histological grade, estrogen receptor
      (ER) status, progesterone receptor (PR) status, Ki-67 expression and human
      epidermal growth factor receptor 2 (HER-2) status. RESULTS: 285 (85.8%) patients
      showed strong CD8+ CTLs infiltrate positive status. Univariate analysis showed
      that CD8+ CTLs had statistically significant association with DFS (P = 0.004,
      hazard ratio [HR] = 0.454, 95% confidence interval [CI] = 0.265-0.777) and OS (P
      = 0.014, HR = 0.430, 95% CI = 0.220-0.840) in the entire cohort. The significance
      of CD8+ CTLs was especially strong in ER negative, HER-2 negative and ER, PR, HER
      2 triple-negative breast cancers. In Kaplan-Meier analysis, CD8+ CTLs had
      significant effect on prognosis of patients (Log-rank test: P = 0.003 for DFS and
      P = 0.011 for OS), independent of established clinical factors for DFS (P =
      0.002, HR = 0.418, 95% CI = 0.242-0.724) as well as for OS (P = 0.009, HR =
      0.401, 95% CI = 0.202-0.797).

PMID- 24743336
TI  - Shared sanitation versus individual household latrines: a systematic review of
      health outcomes.
AB  - BACKGROUND: More than 761 million people rely on shared sanitation facilities.
      These have historically been excluded from international sanitation targets,
      regardless of the service level, due to concerns about acceptability, hygiene and
      access. In connection with a proposed change in such policy, we undertook this
      review to identify and summarize existing evidence that compares health outcomes
      associated with shared sanitation versus individual household latrines. METHODS
      AND FINDINGS: Shared sanitation included any type of facilities intended for the
      containment of human faeces and used by more than one household, but excluded
      public facilities. Health outcomes included diarrhoea, helminth infections,
      enteric fevers, other faecal-oral diseases, trachoma and adverse maternal or
      birth outcomes. Studies were included regardless of design, location, language or
      publication status. Studies were assessed for methodological quality using the
      STROBE guidelines. Twenty-two studies conducted in 21 countries met the inclusion
      criteria. Studies show a pattern of increased risk of adverse health outcomes
      associated with shared sanitation compared to individual household latrines. A
      meta-analysis of 12 studies reporting on diarrhoea found increased odds of
      disease associated with reliance on shared sanitation (odds ratio (OR) 1.44, 95%
      CI: 1.18-1.76). CONCLUSION: Evidence to date does not support a change of
      existing policy of excluding shared sanitation from the definition of improved
      sanitation used in international monitoring and targets. However, such evidence
      is limited, does not adequately address likely confounding, and does not identify
      potentially important distinctions among types of shared facilities. As reliance
      on shared sanitation is increasing, further research is necessary to determine
      the circumstances, if any, under which shared sanitation can offer a safe,
      appropriate and acceptable alternative to individual household latrines.

PMID- 24743337
TI  - A site-specific, single-copy transgenesis strategy to identify 5' regulatory
      sequences of the mouse testis-determining gene Sry.
AB  - The Y-chromosomal gene SRY acts as the primary trigger for male sex determination
      in mammalian embryos. Correct regulation of SRY is critical: aberrant timing or
      level of Sry expression is known to disrupt testis development in mice and we
      hypothesize that mutations that affect regulation of human SRY may account for
      some of the many cases of XY gonadal dysgenesis that currently remain
      unexplained. However, the cis-sequences involved in regulation of Sry have not
      been identified, precluding a test of this hypothesis. Here, we used a transgenic
      mouse approach aimed at identifying mouse Sry 5' flanking regulatory sequences
      within 8 kb of the Sry transcription start site (TSS). To avoid problems
      associated with conventional pronuclear injection of transgenes, we used a
      published strategy designed to yield single-copy transgene integration at a
      defined, transcriptionally open, autosomal locus, Col1a1. None of the Sry
      transgenes tested was expressed at levels compatible with activation of Sox9 or
      XX sex reversal. Our findings indicate either that the Col1a1 locus does not
      provide an appropriate context for the correct expression of Sry transgenes, or
      that the cis-sequences required for Sry expression in the developing gonads lie
      beyond 8 kb 5' of the TSS. 

PMID- 24743338
TI  - Connecting the dots: potential of data integration to identify regulatory SNPs in
      late-onset Alzheimer's disease GWAS findings.
AB  - Late-onset Alzheimer's disease (LOAD) is a multifactorial disorder with over
      twenty loci associated with disease risk. Given the number of genome-wide
      significant variants that fall outside of coding regions, it is possible that
      some of these variants alter some function of gene expression rather than tagging
      coding variants that alter protein structure and/or function. RegulomeDB is a
      database that annotates regulatory functions of genetic variants. In this study,
      we utilized RegulomeDB to investigate potential regulatory functions of lead
      single nucleotide polymorphisms (SNPs) identified in five genome-wide association
      studies (GWAS) of risk and age-at onset (AAO) of LOAD, as well as SNPs in LD
      (r2>=0.80) with the lead GWAS SNPs. Of a total 614 SNPs examined, 394 returned
      RegulomeDB scores of 1-6. Of those 394 variants, 34 showed strong evidence of
      regulatory function (RegulomeDB score <3), and only 3 of them were genome-wide
      significant SNPs (ZCWPW1/rs1476679, CLU/rs1532278 and ABCA7/rs3764650). This
      study further supports the assumption that some of the non-coding GWAS SNPs are
      true associations rather than tagged associations and demonstrates the
      application of RegulomeDB to GWAS data. 

PMID- 24743340
TI  - A comparison of multiple methods for estimating parasitemia of hemogregarine
      hemoparasites (apicomplexa: adeleorina) and its application for studying
      infection in natural populations.
AB  - Identifying factors influencing infection patterns among hosts is critical for
      our understanding of the evolution and impact of parasitism in natural
      populations. However, the correct estimation of infection parameters depends on
      the performance of detection and quantification methods. In this study, we
      designed a quantitative PCR (qPCR) assay targeting the 18 S rRNA gene to estimate
      prevalence and intensity of Hepatozoon infection and compared its performance
      with microscopy and PCR. Using qPCR, we also compared various protocols that
      differ in the biological source and the extraction methods. Our results show that
      the qPCR approach on DNA extracted from blood samples, regardless of the
      extraction protocol, provided the most sensitive estimates of Hepatozoon
      infection parameters; while allowed us to differentiate between mixed infections
      of Adeleorinid (Hepatozoon) and Eimeriorinid (Schellackia and Lankesterella),
      based on the analysis of melting curves. We also show that tissue and saline
      methods can be used as low-cost alternatives in parasitological studies. The next
      step was to test our qPCR assay in a biological context, and for this purpose we
      investigated infection patterns between two sympatric lacertid species, which are
      naturally infected with apicomplexan hemoparasites, such as the genera
      Schellackia (Eimeriorina) and Hepatozoon (Adeleorina). From a biological
      standpoint, we found a positive correlation between Hepatozoon intensity of
      infection and host body size within each host species, being significantly higher
      in males, and higher in the smaller sized host species. These variations can be
      associated with a number of host intrinsic factors, like hormonal and
      immunological traits, that require further investigation. Our findings are
      relevant as they pinpoint the importance of accounting for methodological issues
      to better estimate infection in parasitological studies, and illustrate how
      between-host factors can influence parasite distributions in sympatric natural
      populations. 

PMID- 24743339
TI  - Modified vaccinia virus Ankara triggers type I IFN production in murine
      conventional dendritic cells via a cGAS/STING-mediated cytosolic DNA-sensing
      pathway.
AB  - Modified vaccinia virus Ankara (MVA) is an attenuated poxvirus that has been
      engineered as a vaccine against infectious agents and cancers. Our goal is to
      understand how MVA modulates innate immunity in dendritic cells (DCs), which can
      provide insights to vaccine design. In this study, using murine bone marrow
      derived dendritic cells, we assessed type I interferon (IFN) gene induction and
      protein secretion in response to MVA infection. We report that MVA infection
      elicits the production of type I IFN in murine conventional dendritic cells
      (cDCs), but not in plasmacytoid dendritic cells (pDCs). Transcription factors
      IRF3 (IFN regulatory factor 3) and IRF7, and the positive feedback loop mediated
      by IFNAR1 (IFN alpha/beta receptor 1), are required for the induction. MVA
      induction of type I IFN is fully dependent on STING (stimulator of IFN genes) and
      the newly discovered cytosolic DNA sensor cGAS (cyclic guanosine monophosphate
      adenosine monophosphate synthase). MVA infection of cDCs triggers phosphorylation
      of TBK1 (Tank-binding kinase 1) and IRF3, which is abolished in the absence of
      cGAS and STING. Furthermore, intravenous delivery of MVA induces type I IFN in
      wild-type mice, but not in mice lacking STING or IRF3. Treatment of cDCs with
      inhibitors of endosomal and lysosomal acidification or the lysosomal enzyme
      Cathepsin B attenuated MVA-induced type I IFN production, indicating that
      lysosomal enzymatic processing of virions is important for MVA sensing. Taken
      together, our results demonstrate a critical role of the cGAS/STING-mediated
      cytosolic DNA-sensing pathway for type I IFN induction in cDCs by MVA. We present
      evidence that vaccinia virulence factors E3 and N1 inhibit the activation of IRF3
      and the induction of IFNB gene in MVA-infected cDCs. 

PMID- 24743341
TI  - Continuous attractor network model for conjunctive position-by-velocity tuning of
      grid cells.
AB  - The spatial responses of many of the cells recorded in layer II of rodent medial
      entorhinal cortex (MEC) show a triangular grid pattern, which appears to provide
      an accurate population code for animal spatial position. In layer III, V and VI
      of the rat MEC, grid cells are also selective to head-direction and are modulated
      by the speed of the animal. Several putative mechanisms of grid-like maps were
      proposed, including attractor network dynamics, interactions with theta
      oscillations or single-unit mechanisms such as firing rate adaptation. In this
      paper, we present a new attractor network model that accounts for the conjunctive
      position-by-velocity selectivity of grid cells. Our network model is able to
      perform robust path integration even when the recurrent connections are subject
      to random perturbations. 

PMID- 24743343
TI  - Methods to determine the transcriptomes of trypanosomes in mixtures with
      mammalian cells: the effects of parasite purification and selective cDNA
      amplification.
AB  - Patterns of gene expression in cultured Trypanosoma brucei bloodstream and
      procyclic forms have been extensively characterized, and some comparisons have
      been made with trypanosomes grown to high parasitaemias in laboratory rodents. We
      do not know, however, to what extent these transcriptomes resemble those in
      infected Tsetse flies - or in humans or cattle, where parasitaemias are
      substantially lower. For clinical and field samples it is difficult to
      characterize parasite gene expression because of the large excess of host cell
      RNA. We have here examined two potential solutions to this problem for
      bloodstream form trypanosomes, assaying transcriptomes by high throughput cDNA
      sequencing (RNASeq). We first purified the parasites from blood of infected rats.
      We found that a red blood cell lysis procedure affected the transcriptome
      substantially more than purification using a DEAE cellulose column, but that too
      introduced significant distortions and variability. As an alternative, we
      specifically amplified parasite sequences from a mixture containing a 1000-fold
      excess of human RNA. We first purified polyadenylated RNA, then made trypanosome
      specific cDNA by priming with a spliced leader primer. Finally, the cDNA was
      amplified using nested primers. The amplification procedure was able to produce
      samples in which 20% of sequence reads mapped to the trypanosome genome.
      Synthesis of the second cDNA strand with a spliced leader primer, followed by
      amplification, is sufficiently reproducible to allow comparison of different
      samples so long as they are all treated in the same way. However, SL priming
      distorted the abundances of the cDNA products and definitely cannot be used, by
      itself, to measure absolute mRNA levels. The amplification method might be
      suitable for clinical samples with low parasitaemias, and could also be adapted
      for other Kinetoplastids and to samples from infected vectors. 

PMID- 24743344
TI  - Highly differentiated ZW sex microchromosomes in the Australian Varanus species
      evolved through rapid amplification of repetitive sequences.
AB  - Transitions between sex determination systems have occurred in many lineages of
      squamates and it follows that novel sex chromosomes will also have arisen
      multiple times. The formation of sex chromosomes may be reinforced by inhibition
      of recombination and the accumulation of repetitive DNA sequences. The karyotypes
      of monitor lizards are known to be highly conserved yet the sex chromosomes in
      this family have not been fully investigated. Here, we compare male and female
      karyotypes of three Australian monitor lizards, Varanus acanthurus, V. gouldii
      and V. rosenbergi, from two different clades. V. acanthurus belongs to the
      acanthurus clade and the other two belong to the gouldii clade. We applied C
      banding and comparative genomic hybridization to reveal that these species have
      ZZ/ZW sex micro-chromosomes in which the W chromosome is highly differentiated
      from the Z chromosome. In combination with previous reports, all six Varanus
      species in which sex chromosomes have been identified have ZZ/ZW sex chromosomes,
      spanning several clades on the varanid phylogeny, making it likely that the ZZ/ZW
      sex chromosome is ancestral for this family. However, repetitive sequences of
      these ZW chromosome pairs differed among species. In particular, an (AAT)n
      microsatellite repeat motif mapped by fluorescence in situ hybridization on part
      of W chromosome in V. acanthurus only, whereas a (CGG)n motif mapped onto the W
      chromosomes of V. gouldii and V. rosenbergi. Furthermore, the W chromosome probe
      for V. acanthurus produced hybridization signals only on the centromeric regions
      of W chromosomes of the other two species. These results suggest that the W
      chromosome sequences were not conserved between gouldii and acanthurus clades and
      that these repetitive sequences have been amplified rapidly and independently on
      the W chromosome of the two clades after their divergence. 

PMID- 24743342
TI  - Genome-wide profiling of yeast DNA:RNA hybrid prone sites with DRIP-chip.
AB  - DNA:RNA hybrid formation is emerging as a significant cause of genome instability
      in biological systems ranging from bacteria to mammals. Here we describe the
      genome-wide distribution of DNA:RNA hybrid prone loci in Saccharomyces cerevisiae
      by DNA:RNA immunoprecipitation (DRIP) followed by hybridization on tiling
      microarray. These profiles show that DNA:RNA hybrids preferentially accumulated
      at rDNA, Ty1 and Ty2 transposons, telomeric repeat regions and a subset of open
      reading frames (ORFs). The latter are generally highly transcribed and have high
      GC content. Interestingly, significant DNA:RNA hybrid enrichment was also
      detected at genes associated with antisense transcripts. The expression of
      antisense-associated genes was also significantly altered upon overexpression of
      RNase H, which degrades the RNA in hybrids. Finally, we uncover mutant-specific
      differences in the DRIP profiles of a Sen1 helicase mutant, RNase H deletion
      mutant and Hpr1 THO complex mutant compared to wild type, suggesting different
      roles for these proteins in DNA:RNA hybrid biology. Our profiles of DNA:RNA
      hybrid prone loci provide a resource for understanding the properties of hybrid
      forming regions in vivo, extend our knowledge of hybrid-mitigating enzymes, and
      contribute to models of antisense-mediated gene regulation. A summary of this
      paper was presented at the 26th International Conference on Yeast Genetics and
      Molecular Biology, August 2013. 

PMID- 24743345
TI  - Potential for pancreatic maturation of differentiating human embryonic stem cells
      is sensitive to the specific pathway of definitive endoderm commitment.
AB  - This study provides a detailed experimental and mathematical analysis of the
      impact of the initial pathway of definitive endoderm (DE) induction on later
      stages of pancreatic maturation. Human embryonic stem cells (hESCs) were induced
      to insulin-producing cells following a directed-differentiation approach. DE was
      induced following four alternative pathway modulations. DE derivatives obtained
      from these alternate pathways were subjected to pancreatic progenitor (PP)
      induction and maturation and analyzed at each stage. Results indicate that late
      stage maturation is influenced by the initial pathway of DE commitment. Detailed
      quantitative analysis revealed WNT3A and FGF2 induced DE cells showed highest
      expression of insulin, are closely aligned in gene expression patterning and have
      a closer resemblance to pancreatic organogenesis. Conversely, BMP4 at DE
      induction gave most divergent differentiation dynamics with lowest insulin
      upregulation, but highest glucagon upregulation. Additionally, we have concluded
      that early analysis of PP markers is indicative of its potential for pancreatic
      maturation. 

PMID- 24743346
TI  - Identification of gene expression changes from colitis to CRC in the mouse CAC
      model.
AB  - A connection between colorectal carcinogenesis and inflammation is well known,
      but the underlying molecular mechanisms have not been elucidated. Chemically
      induced colitis-associated cancer (CAC) is an outstanding mouse model for
      studying the link between inflammation and cancer. Additionally, the CAC model is
      used for examining novel diagnostic, prognostic, and predictive markers for use
      in clinical practice. Here, a CAC model was established in less than 100 days
      using azoxymethane (AOM) with dextran sulfate sodium salt (DSS) in BALB/c mice.
      We examined the mRNA expression profiles of three groups: control untreated mice
      (K), DSS-induced chronic colitis mice (D), and AOM/DSS-induced CAC (AD) mice. We
      identified 6301 differentially expressed genes (DEGs) among the three groups,
      including 93 persistently upregulated genes and 139 persistently downregulated
      genes. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG)
      pathway analyses revealed that the most persistent DEGs were significantly
      enriched in metabolic or inflammatory components in the tumor microenvironment.
      Furthermore, several associated DEGs were identified as potential DEGs by protein
      protein interaction (PPI) network analysis. We selected 14 key genes from the
      DEGs and potential DEGs for further quantitative real-time PCR (qPCR)
      verification. Six persistently upregulated, 3 persistently downregulated DEGs,
      and the other 3 genes showed results consistent with the microarray data. We
      demonstrated the regulation of 12 key genes specifically involved in Wnt
      signaling, cytokine and cytokine receptor interactions, homeostasis, and tumor
      associated metabolism during colitis-associated CRC. Our results suggest that a
      close relationship between metabolic and inflammatory mediators of the tumor
      microenvironment is present in CAC.

PMID- 24743347
TI  - Downregulation of complement C3 and C3aR expression in subcutaneous adipose
      tissue in obese women.
AB  - BACKGROUND: The central component of the complement system, C3, is associated
      with obesity, metabolic syndrome and cardiovascular disease however the
      underlying reasons are unknown. In the present study we evaluated gene expression
      of C3, the cleavage product C3a/C3adesArg and its cognate receptor C3aR in
      subcutaneous and omental adipose tissue in women. METHODS: Women (n = 140, 21-69
      years, BMI 19.5-79 kg/m2) were evaluated for anthropometric and blood parameters,
      and adipose tissue gene expression. RESULTS: Subjects were separated into groups
      (n = 34-36) according to obesity: normal/overweight (<=30 kg/m2), obese I (<=45
      kg/m2), obese II (<=51 kg/m2), and obese III (<=80 kg/m2). Overall, while omental
      expression remained unchanged, subcutaneous C3 and C3aR gene expression decreased
      with increasing adiposity (2-way ANOVA, p<0.01), with a concomitant decrease in
      SC/OM ratio (p<0.001). In subcutaneous adipose, both C3 and C3aR expression
      correlated with apoB, and apoA1 and inversely with waist circumference and blood
      pressure, while C3aR also correlated with glucose (p<0.05-0.0001). While omental
      C3aR expression did not correlate with any factor, omental C3 correlated with
      waist circumference, glucose and apoB (all p<0.05). Further, while plasma
      C3a/C3adesArg increased and adiponectin decreased with increasing BMI, both
      correlated (C3a negatively and adiponectin positively) with subcutaneous C3 and
      C3aR expression (p<0.05-0.001) or less). CONCLUSIONS: The obesity-induced down
      regulation of complement C3 and C3aR which is specific to subcutaneous adipose
      tissue, coupled to the strong correlations with multiple anthropometric, plasma
      and adipokine variables support a potential role for complement in
      immunometabolism.

PMID- 24743348
TI  - Restoration enhances wetland biodiversity and ecosystem service supply, but
      results are context-dependent: a meta-analysis.
AB  - Wetlands are valuable ecosystems because they harbor a huge biodiversity and
      provide key services to societies. When natural or human factors degrade
      wetlands, ecological restoration is often carried out to recover biodiversity and
      ecosystem services (ES). Although such restorations are routinely performed, we
      lack systematic, evidence-based assessments of their effectiveness on the
      recovery of biodiversity and ES. Here we performed a meta-analysis of 70
      experimental studies in order to assess the effectiveness of ecological
      restoration and identify what factors affect it. We compared selected ecosystem
      performance variables between degraded and restored wetlands and between restored
      and natural wetlands using response ratios and random-effects categorical
      modeling. We assessed how context factors such as ecosystem type, main agent of
      degradation, restoration action, experimental design, and restoration age
      influenced post-restoration biodiversity and ES. Biodiversity showed excellent
      recovery, though the precise recovery depended strongly on the type of organisms
      involved. Restored wetlands showed 36% higher levels of provisioning, regulating
      and supporting ES than did degraded wetlands. In fact, wetlands showed levels of
      provisioning and cultural ES similar to those of natural wetlands; however, their
      levels of supporting and regulating ES were, respectively, 16% and 22% lower than
      in natural wetlands. Recovery of biodiversity and of ES were positively
      correlated, indicating a win-win restoration outcome. The extent to which
      restoration increased biodiversity and ES in degraded wetlands depended primarily
      on the main agent of degradation, restoration actions, experimental design, and
      ecosystem type. In contrast, the choice of specific restoration actions alone
      explained most differences between restored and natural wetlands. These results
      highlight the importance of comprehensive, multi-factorial assessment to
      determine the ecological status of degraded, restored and natural wetlands and
      thereby evaluate the effectiveness of ecological restorations. Future research on
      wetland restoration should also seek to identify which restoration actions work
      best for specific habitats. 

PMID- 24743349
TI  - Educational differences in incidence of cancer in Lithuania, 2001-2009: evidence
      from census-linked cancer registry data.
AB  - This study used population-based census-linked cancer incidence data to identify
      patterns of educational differentials in the risk of cancer by detailed sites of
      cancer in Lithuania. The study is based on the linkage between all records of the
      2001 population census, all records from the Lithuanian Cancer Registry (cancer
      incidence), and all death and emigration records from Statistics Lithuania for
      the period between 6 April 2001 and 31 December 2009. The study population
      (cohort) includes all permanent residents of Lithuania aged 30-74 years on the
      day of the census (6 April 2001). The study found that cancers of the lip, mouth,
      and pharynx, esophagus, stomach, larynx, urinary bladder, pancreas, and lung for
      men and cancers of the cervix uteri, lung, and colon for women show a
      statistically significant inverse educational gradient with excess incidence in
      the lowest educational group. At the same time, a reversed cancer risk gradient
      with the highest incidence for the higher education group was observed for
      thyroid cancer, melanoma, nonmelanoma skin cancers, and non-Hodgkin lymphomas.
      This group also includes prostate cancer, kidney cancer, and multiple myeloma for
      men and cancer of the pancreas, breast cancer, cancer of the colon, and cancer of
      the uterus for women. The associations between education and cancer incidence
      observed in this study reflect the concordance between social status and
      lifestyle-related risk factors for cancer. Cancer awareness in society has also
      contributed toward the observed higher risk of cancer, which is usually promoted
      more by patients with higher education. 

PMID- 24743350
TI  - Alcohol consumption and breast cancer risk subtypes in the E3N-EPIC cohort.
AB  - The aim of this study was to obtain an overview of the associations between
      alcohol consumption and breast cancer risk at adulthood, by type of alcohol and
      subtype of breast cancer. Between 1993 and 2008, 66,481 women from the French E3N
      EPIC cohort were followed up and asked to report their alcohol consumption, by
      type of alcohol, through a 208-item diet-history questionnaire. A total of 2812
      breast cancer cases were validated during the follow-up session. No association
      was found between high alcohol consumption, whatever its type, and increase in
      breast cancer risk in the premenopausal period. During the postmenopausal period,
      a linear association between total alcohol consumption and breast cancer risk was
      found (P<0.0001), mainly driven by the associations with wine and beer [hazard
      ratio=1.33 (1.11-1.58) and 1.85 (1.19-2.89)] for more than two glasses per day of
      wine and beer, respectively, compared with nondrinkers] and with ER+/PR+ breast
      cancer subtypes. In the postmenopausal period, we observed interactions between
      total alcohol and folate intake levels (P=0.1192) and BMI (P=0.0367), with higher
      increased risks observed for high alcohol intake among women with low folate
      intake or who were overweight or obese. Our results make precise the current body
      of knowledge on the relationship between alcohol and breast cancer subtypes.
      Interactions between alcohol and other factors should further be taken into
      account in public health nutrition programs.

PMID- 24743351
TI  - Wormholes in host defense: how helminths manipulate host tissues to survive and
      reproduce.

PMID- 24743352
TI  - Behavioral plasticity in ant queens: environmental manipulation induces
      aggression among normally peaceful queens in the socially polymorphic ant
      Leptothorax acervorum.
AB  - The behavioral traits that shape the structure of animal societies vary
      considerably among species but appear to be less flexible within species or at
      least within populations. Populations of the ant Leptothorax acervorum differ in
      how queens interact with other queens. Nestmate queens from extended, homogeneous
      habitats tolerate each other and contribute quite equally to the offspring of the
      colony (polygyny: low reproductive skew). In contrast, nestmate queens from
      patchy habitats establish social hierarchies by biting and antennal boxing, and
      eventually only the top-ranking queen of the colony lays eggs (functional
      monogyny: high reproductive skew). Here we investigate whether queen-queen
      behavior is fixed within populations or whether aggression and high skew can be
      elicited by manipulation of socio-environmental factors in colonies from low skew
      populations. An increase of queen/worker ratio and to a lesser extent food
      limitation elicited queen-queen antagonism in polygynous colonies from Nurnberger
      Reichswald similar to that underlying social and reproductive hierarchies in high
      skew populations from Spain, Japan, and Alaska. In manipulated colonies, queens
      differed more in ovarian status than in control colonies. This indicates that
      queens are in principle capable of adapting the magnitude of reproductive skew to
      environmental changes in behavioral rather than evolutionary time. 

PMID- 24743354
TI  - [Selection of appropriate design in the development of interventional and
      observational research].
AB  - Selecting the appropriate study design is crucial when developing clinical
      research. A fundamental decision is whether to collect data to address the
      research question using an observational study or to apply an intervention and
      measure outcomes in a clinical trial. There are two well-known types of
      observational studies: cohort studies and cross-sectional studies. In the former,
      a cohort of subjects is observed over time. In prospective cohort studies,
      observations begin in the present and follow subjects for a given time period. In
      retrospective cohort studies, information is collected at time intervals in the
      past. The third potential study design is the case-control study. In such
      studies, the researcher compares a group of subjects who have a disease or some
      other outcome with a group without that characteristic. Among clinical trial
      options, the randomized clinical trial is thought to be higher evidence level
      than other clinical trials. Developing clinical research begins with the research
      question, which specifies the primary endpoint, explanatory variables, and the
      target population. Then, the clinical question and study outline are expanded to
      the study protocol and case report form. In developing the study protocol, the
      investigators consider study design, study size, data quality, and feasibility. 

PMID- 24743353
TI  - Effects of short- and long-term variations in RLS severity on perceived health
      status - the COR-study.
AB  - In a cohort study among 2751 members (71.5% females) of the German and Swiss RLS
      patient organizations changes in restless legs syndrome (RLS) severity over time
      was assessed and the impact on quality of life, sleep quality and depressive
      symptoms was analysed. A standard set of scales (RLS severity scale IRLS, SF-36,
      Pittsburgh Sleep Quality Index and the Centre for Epidemiologic Studies
      Depression Scale) in mailed questionnaires was repeatedly used to assess RLS
      severity and health status over time and a 7-day diary once to assess short-term
      variations. A clinically relevant change of the RLS severity was defined by a
      change of at least 5 points on the IRLS scale. During 36 months follow-up minimal
      improvement of RLS severity between assessments was observed. Men consistently
      reported higher severity scores. RLS severity increased with age reaching a
      plateau in the age group 45-54 years. During 3 years 60.2% of the participants
      had no relevant (+/-5 points) change in RLS severity. RLS worsening was
      significantly related to an increase in depressive symptoms and a decrease in
      sleep quality and quality of life. The short-term variation showed distinctive
      circadian patterns with rhythm magnitudes strongly related to RLS severity. The
      majority of participants had a stable course of severe RLS over three years. An
      increase in RLS severity was accompanied by a small to moderate negative, a
      decrease by a small positive influence on quality of life, depressive symptoms
      and sleep quality. 

PMID- 24743355
TI  - [The current state of transfusion medicine in Japan].
AB  - In Japan, transfusion medicine, which is supported by the voluntary blood
      donation system, is facing a risk of blood shortage. This is due to reduced
      donations by the younger generation as well as the falling birth rate and the
      aging of the population, with a consequent increase in the elderly population
      that depends on blood transfusions for conditions such as cancer and
      hematological and cardiovascular diseases. Therefore, to guarantee stable
      provision of blood products, in addition to implementing measures to promote
      blood donation, healthcare professionals must, as a policy, strictly follow the
      rules for appropriate use of blood products as defined in the "Criteria for the
      Use of Blood Products". Additionally, measures such as the use of autologous
      blood to reduce allogeneic blood usage and the implementation of adequate
      internal control systems to reduce blood wastage should be considered. Further,
      although this is not presently covered by the Japanese Health Insurance System,
      cryoprecipitate or fibrinogen products, which are used as alternative therapies
      in cases of hypofibrinogenemia due to massive bleeding, are effective not only
      for reducing the blood transfusion volume, but also for alleviating bleeding in
      patients. Additionally, the use of erythropoietin to treat chemotherapy-induced
      anemia is an effective measure to improve patients' quality of life, and its
      prompt approval by the Health Insurance System is desired. 

PMID- 24743356
TI  - [Treatment of chemotherapy-induced anemia].
AB  - The prognosis of cancer patients with anemia is poor. In Japan, these patients
      are treated only with red blood cell transfusions, and doctors cannot use
      erythropoiesis stimulating agents(ESAs)such as epoetin and darbepoetin. On the
      other hand, ESAs are widely used in the USA and Europe to treat patients with
      chemotherapy-induced anemia. However, the results of randomized controlled
      trials(RCTs)and meta-analysis have suggested that the use of ESAs was correlated
      with increasing incidence of venous thromboembolism(VTE)and mortality. The
      American Society of Clinical Oncology(ASCO)and the American Society of
      Hematology(ASH)guidelines, revised in 2010, recommend the minimal use of ESAs for
      patients with chemotherapy-induced anemia, except for anemic cancer patients who
      are not currently receiving chemotherapy. A change in the target
      hemoglobin(Hb)level to achieve a concentration of 12 g/dL was recommended in 2007
      as the lowest concentration required to avoid transfusions. We discuss the cause
      of anemia in cancer patients, and examine the current state of the clinical use
      and problems associated with ESAs. 

PMID- 24743357
TI  - [Questionnaire-based survey on chemotherapy-induced anemia].
AB  - The Japan Society of Clinical Oncology and The Japan Society of Transfusion
      Medicine and Cell Therapy jointly conducted a questionnaire-based survey on
      chemotherapy-induced anemia(CIA)in cancer patients between September and November
      2010, the results of which are outlined here. For all the eight main cancer types
      in Japan that were analyzed(breast, lung, stomach, colorectal, liver,
      gynecologic, and urologic cancers and malignant lymphoma), blood transfusion was
      required in 1.6-24.0%(mean=7.5%)of patients who received chemotherapy, and 3.9
      7.3 units(mean=5.9 units)red blood cells were transfused per patient.
      Approximately 146,000 units of red blood cells, accounting for 2.2%of the total
      annual supply of red blood cell products, was estimated to be transfused to
      cancer patients with CIA every year. In addition, approximately 172,000 cancer
      patients with CIA, accounting for 40% of patients receiving chemotherapy, were
      estimated to have hemoglobin(Hb)levels below 10 g/dL annually. In patients who
      received red blood cell transfusions, the average Hb level prior to chemotherapy
      was 9.5 g/dL and the average lowest Hb level after starting chemotherapy was 6.9
      g/dL; these values were 11.6 g/dL and 10.4 g/dL, respectively, in patients who
      did not receive transfusion. Furthermore, for all cancer types, almost no red
      blood cell transfusions were performed in patients with an Hb level of 8.0 g/dL
      or higher, although many patients with an Hb level of 6.9 g/dL or lower also did
      not receive red blood cell transfusions. These results highlight the strict
      restriction of red blood cell transfusion to cancer patients with CIA. Therefore,
      the use of alternative therapies such as erythropoiesis-stimulating agents should
      be considered to improve the quality of life of cancer patients with CIA.

PMID- 24743358
TI  - [Treatment of cancer chemotherapy-associated anemia in Japan - conditions and
      issues].
AB  - Cancer chemotherapy-induced anemia(CIA)is observed in approximately 70%of
      patients treated with cytotoxic chemo- therapy. The hemoglobin concentration in
      the peripheral blood is C10 g/dL in 40% of these patients, and C8 g/dL in 23% of
      these patients. Red blood cell transfusion is performed in 16% of these patients.
      Since erythropoiesis-stimulating agents (ESA)are not approved in Japan, blood
      transfusion is the only choice of treatment for CIA. In Northwestern countries,
      ESA have been utilized for the treatment of CIA for >20 years. Recently, however,
      the use of ESA has become regulated towing to concerns about the potential life
      shortening effects, although ESA are still the treatment of choice for CIA. In
      this paper, the characteristics of CIA in Japan and the underlying issues have
      been discussed. 

PMID- 24743359
TI  - [A retrospective study of tegafur/uracil compared with cyclophosphamide,
      methotrexate, and fluorouracil as adjuvant chemotherapy in patients with node
      negative, triple-negative breast cancer].
AB  - Japanese clinical trials of a tegafur/uracil(UFT)-based postoperative
      chemotherapy regimen compared with cyclophosphamide, methotrexate, and
      fluorouracil(CMF)treatment have shown that UFT is not inferior to CMF for the
      treatment of hormone receptor-positive breast cancer patients. However, the
      usefulness of UFT for hormone receptor-negative breast cancer, including the
      triple-negative subtype(hormone receptor-negative, human epidermal growth factor
      receptor 2 [HER2]-negative), is unknown. The aim of this retrospective study was
      to examine the effectiveness of postoperative, adjuvant UFT compared to CMF when
      these regimens were given to women with node-negative, triple-negative breast
      cancer. We analyzed 50 women with node-negative, triple-negative breast cancer
      who were treated with six cycles of CMF(n=33) or two years of UFT(n=17)after
      surgery between January 2000 and December 2010. Although no significant
      differences were observed in relapse-free survival or overall survival in all
      patients, subset analysis of tumors of larger size(t2), higher nuclear
      grade(NG3), and with positivity for lymphovascular invasion showed that UFT was
      inferior to CMF. These results encourage caution regarding the choice of adjuvant
      UFT for node-negative, triple-negative breast cancer. 

PMID- 24743360
TI  - [Clinical evaluation of eribulin mesylate for the treatment of metastatic breast
      cancer].
AB  - BACKGROUND: Eribulin mesylate, a novel non-taxane inhibitor of microtubule
      dynamics, results in a significant improvement in the overall survival of heavily
      pretreated patients with metastatic breast cancer(MBC). In the present study, we
      aimed to clarify the efficacy and safety of eribulin mesylate for the treatment
      of MBC. PATIENTS AND METHODS: We examined 18 patients with MBC who received
      eribulin mesylate in our hospital from October 2011 to May 2013. The patients
      were assessed for therapeutic response and adverse events with this treatment; in
      addition, these parameters were assessed in patients undergoing a combination
      treatment of eribulin mesylate and trastuzumab. RESULTS: The mean age of the
      patients in this study was 68.7 years(range, 60-85 years). All patients exhibited
      metastases to lymph nodes and distant sites. The mean number of prior regimens
      was 4.4(range, 2-9). The mean number of cycles of eribulin mesylate treatment
      administered was 7.2(range, 2- 17). The objective response rate and clinical
      benefit rate(PR+long SD)were 33.3%(6/18)and 50.0%(9/18), respectively, and the
      median progression-free survival was 6 months. The Grade 3/4 adverse events
      occurring in the patients included neutropenia in 13 patients(72.2%), anemia in 1
      patient(5.6%), anorexia in 1 patient(5.6%), stomatitis in 1 patient(5.6%), and
      peripheral neuropathy in 1 patient(5.6%). However, 3 elderly patients who
      received the combination treatment of trastuzumab and eribulin mesylate
      experienced no adverse events. CONCLUSIONS: eribulin mesylate appears to
      demonstrate an acceptable tumor response in patients with MBC, and it can be
      safely administered to elderly patients if myelosuppression is carefully managed.

PMID- 24743361
TI  - [Effect of the administration of zoledronic acid on life expectancy in patients
      with multiple myeloma with or without renal impairment].
AB  - Zoledronic acid(ZA)is believed to exert anticancer effects in patients with
      multiple myeloma(MM). For patients with impaired renal function, its dosage
      should be determined according to creatinine clearance(Ccr). However, there is no
      reported difference in life expectancy improvement between those with and without
      renal impairment. Therefore, we conducted a retrospective study to investigate
      this clinical question. Seventy-eight MM patients receiving ZA injections were
      selected and divided into 2 groups: (1)normal group(n=39), baseline
      Ccr>=60mL/min, and(2)impaired group(n=39), baseline Ccr<60mL/min. Patients in the
      normal group received a significantly higher initial dose(p<0.001), were of a
      younger age(p<0.001), had lower b2-microglobulin(b2-M)levels(p<0.001), and had
      higher rates of prior hematopoietic stem cell transplantation(p<0.001)than those
      in the impaired group. We then compared the survival rate between 31 patients in
      the normal group and 27 patients in the impaired group whose treatment outcome
      data were available and found no significant difference(p=0.251). Therefore, our
      results suggest that the survival rate on ZA administration may not differ
      between MM patients with and without renal impairment. 

PMID- 24743362
TI  - [Establishment of induced pluripotent stem cells from adipose tissue-derived stem
      cells for dendritic cell-based cancer vaccines].
AB  - Recently, studies on regenerative stem cell therapy are being encouraged, and
      efforts to generate dendritic cells, which play important roles in cancer
      immunotherapy, from stem cells are being made in the field of tumor immunology.
      Therapeutic acquisition of stem cells has important clinical applications.
      Studies on induced pluripotent stem(iPS)cells generated from somatic cells with
      pluripotent genes have advanced in recent years. Stem cells are reported to be
      found in adipose tissue (adipose-derived stem cells, ADSC). Our goal is to
      develop a new cancer vaccine by using dendritic cells generated from ADSC. In a
      preliminary study, we examined whether iPS cells can be generated from ADSC to
      serve as a source of dendritic cells.We introduced a plasmid with pluripotent
      genes(OCT3/4, KLF4, SOX2, L-MYC, LIN28, p53-shRNA)into an ADSC strain derived
      from adipose tissue by electroporation and subsequently cultured the cells for
      further examination. A colony sugges- tive of iPS cells from ADSC was observed.
      OCT3/4, KLF4, SOX2, L-MYC, and LIN28 mRNAs were expressed in the cultured cells,
      as confirmed by reverse transcriptase-polymerase chain reaction(RT-PCR). On the
      basis of these results, we confirmed that iPS cells were generated from ADSC. The
      method of inducing dendritic cells from iPS cells has already been reported, and
      the results of this study suggest that ADSC is a potential source of dendritic
      cells. 

PMID- 24743363
TI  - Novel method of determination of D9-tetrahydrocannabinol(THC) in human serum by
      high-performance liquid chromatography with electrochemical detection.
AB  - In Europe and the United States, D9-tetrahydrocannabinol(THC, dronabinol), one of
      the psychoactive constituents of cannabis, has been used for both its anti-emetic
      and orexigenic effects in cancer patient receiving chemotherapy.However,
      dronabinol has not yet been launched in the market in Japan.In the future, it is
      necessary to ascertain the pharmacokinetics of dronabinol in cancer
      paitient.Therefore, we developed an HPLC procedure using electrochemical
      detection(ECD)for quan- titation of the concentrations of dronabinol in blood.An
      eluent of 50mM KH2PO4/CH3CN(9:16)was used as the mobile phase.The column was used
      the XTerra(r)RP18, and the voltage of the electrochemical detector in dronabinol
      was set at 400 mV.As a result, the calibration curve was linear in the range of
      10 ng/mL to 100 ng/mL(y=964.85x -3,419, r=0.997).The lower limit of
      quantification was 0.5 ng/mL(S/N=3).The relative within-runs and between-runs
      standard deviations for the assay dronabinol were less than 4.7%. The method
      reported here is superior to previously reported methods in cancer patient. 

PMID- 24743364
TI  - [Safety and effectiveness of pemetrexed in patients with non-small cell lung
      cancer in Japan - analysis of post-marketing surveillance].
AB  - The safety and effectiveness of pemetrexed(PEM)in patients with non-small cell
      lung cancer(NSCLC)were reviewed using data from post-marketing surveillance.
      Among 699 patients registered from June 2009 to May 2010, 683 patients were
      analyzed(343, first-line therapy: 340, second-line therapy or beyond). Patient
      backgrounds were as follows: median age=65 years(16.1%B75 years old); 64.7% male;
      91.9% performance status 0-1; 83.2% Stage IV; 99.0% non-squamous cell cancer.
      Also, 86% of the first-line and 20% of the second-line cohort were receiving a
      concomitant anti-cancer drug(mostly platinum agents). The incidence rate of
      adverse drug reactions(ADR)was 76.7%, including serious cases(18.0%). The most
      common ADRs were decreased white blood cell count(26.8%), decreased neutrophil
      count(25.3%), anemia(19.2%), decreased platelet count(17.0%), and nausea(23.0%).
      The incidence of interstitial lung disease, which is a concern during
      chemotherapy, was 2.6%. Peripheral neuropathy and alopecia, events influencing a
      patient's quality of life, were less than 1%. The estimated median survival time
      was 23.2 months[95%CI: 19.8 months-not calculable]in the first-line cohort, and
      11.8 months[95% CI: 10.5-13.7 months]in the B second-line cohort. The
      surveillance results showed no apparent difference in total ADRs in this current
      study compared to the safety profile established in clinical trials previously
      conducted in Japan and overseas. These results demonstrate the safety and
      effectiveness of PEM treatment for NSCLC patients in daily clinical settings. 

PMID- 24743365
TI  - [A case of triple-negative breast cancer responding to multidisciplinary
      treatment containing bevacizumab].
AB  - We report a case of a 64-year-old woman with Stage IV breast cancer who responded
      well to chemotherapy containing bevacizumab. She noticed a left breast tumor with
      acute progression and was diagnosed as having Stage IV, estrogen receptor( ER)(
      ), progesterone receptor(PgR)(-), human epidermal growth factor receptor 2(HER2)(
      )breast cancer (T4cN3cM1[lymph nodes]). She received 5 courses of
      adriamycin(60mg/m / 2)plus cyclophosphamide(600mg/m2)(AC therapy)and 4 courses of
      weekly paclitaxel(PTX 90mg/m / 2)plus bevacizumab(AVA 10 mg/m2)as systemic
      therapy. Computed tomography(CT)and magnetic resonance imaging(MRI)revealed a
      complete response(CR). After local resection of the breast tumor and radiation to
      the breast and regional lymph nodes, capecitabine therapy was initiated.
      Currently, at 5 months after surgery, no new lesion has been detected. 

PMID- 24743366
TI  - [A case of postmenopausal breast cancer becoming HER2 positive after neoadjuvant
      hormone therapy].
AB  - A 75-year-old woman presented to a local doctor with a lump in the right breast.
      On physical examination, a tumor measuring 24mm was palpable in the BD area of
      her right breast. Mammography showed category 5 disease, and ultrasonography
      revealed a tumor measuring 24*16 mm. A mammotome biopsy provided a diagnosis of
      invasive ductal carcinoma of the breast(ER 7/PgR 4/HER2 1+), and the tumor was
      classified as stage IIA(T2N0M0)according to the UICC-TNM classification. She was
      recommended surgery but she rejected this option and underwent hormone therapy
      with anastrozole (1mg/day). One year and 8months after beginning the treatment,
      ultrasonography showed the tumor to measure 7.0*5.7 mm, and hormone therapy
      resulted in a partial response(PR). The patient hoped to undergo an operation, so
      she was referred to our hospital, and a right partial mastectomy and sentinel
      node biopsy was performed. A histopathological exami- nation indicated scirrhous
      carcinoma, 18mm, nuclear grade 1, f, ly1, v0, n0, ER 3/PgR 3/HER2 3+. The
      curative effect was grade 1a. The tumor had become HER2 positive, so the patient
      was then administered radiotherapy and trastuzumab and anastrozole as adjuvant
      therapy. Herein, we report our experience with a case of breast cancer that only
      became HER2 positive after hormone therapy, and also provide some bibliographic
      comments on this occurrence. 

PMID- 24743367
TI  - [A case of advanced gastric cancer in which the serum HER2-ECD level could be
      used as a biomarker].
AB  - An 83-year-old woman was diagnosed as having advanced gastric cancer with
      multiple lymph node and hepatic metastases. Histopathological examination
      revealed that the tissue was human epidermal growth factor receptor
      2(HER2)positive. The patient underwent gastrojejunostomy to improve stomach
      obstruction. Thereafter, S-1 and trastuzumab combination chemotherapy was
      administered as first-line treatment; irinotecan(CPT-11), cisplatin, and
      trastuzumab combination chemotherapy, as second-line treatment; and docetaxel
      plus trastuzumab combination chemotherapy, as third-line treatment. Although both
      primary and metastatic lesions decreased in size temporarily, their size
      increased again, and the patient died 1 year and 7 months later. The level of
      serum HER2-extracellular domain(ECD)was a valuable indicator of response to
      chemotherapy. Thus, serum HER2-ECD could be a useful biomarker for HER2-positive
      gastric cancer. 

PMID- 24743368
TI  - [A case of primary duodenal cancer recurrence successfully treated with CapeOX
      therapy].
AB  - A 55-year-old man was admitted to our hospital because of nausea and vomiting. An
      endoscopic examination and computed tomography(CT)scan revealed a duodenal tumor.
      A biopsy confirmed a diagnosis of primary duodenal adenocarcinoma. A
      pancreaticoduodenectomy and partial resection of the ascending colon were
      performed. Ten months after surgery, we observed lymph node recurrence and
      peritoneal dissemination. We then introduced capecitabine and oxaliplatin
      (CapeOX)therapy for treatment of the relapsed disease. A partial response(PR)was
      observed after 2 courses, and was sustained for 5 months. The patient survived
      another 1 year and 4 months after disease recurrence. CapeOX therapy can be an
      effective treatment for primary duodenal cancer.

PMID- 24743369
TI  - [A case of severe enteritis induced by adjuvant chemotherapy for colon cancer].
AB  - A 77-year-old man underwent surgery for sigmoid colon cancer. He was diagnosed
      with Stage IIIa colon cancer; there- fore, we initiated oral administration of
      adjuvant chemotherapy comprising uracil/tegafur(UFT)plus Leucovorin(LV). However,
      chemotherapy was stopped after 21 days because of fatigue and diarrhea. He
      recovered after 3 weeks, and we administered the same regimen with a dose
      reduction. However, he again experienced fatigue and diarrhea after 20 days;
      therefore, chemotherapy was discontinued. Subsequently, he was hospitalized 8
      times for conditions such as diarrhea, hypoalbuminemia, and fever. Computed
      tomography revealed thickening of the transverse colonic wall and colonoscopy
      revealed colitis, which we believe was induced by UFT plus LV. Twelve months
      after the last chemotherapy session, he was diagnosed with Clostridium difficile
      colitis. Therefore, we initiated the oral administration of vancomycin, which
      resulted in rapid recovery from colitis. However, he developed liver metastasis
      and died 29 months after the initiation of chemotherapy. We believe that this
      severe case of intractable colitis was caused by UFT plus LV. Therefore, we
      report this case with a review of the literature on enteritis induced by
      fluorouracil-based anticancer agents in Japan. 

PMID- 24743370
TI  - [Two cases of curative resection by laparoscopic surgery following preoperative
      chemotherapy with bevacizumab for locally advanced colon cancer].
AB  - Here we report 2 cases of curative resection following preoperative chemotherapy
      with bevacizumab for locally advanced colon cancer. Case 1 was a 62-year-old man
      admitted with constipation, abdominal distention, and abdominal pain. An
      abdominal computed tomography(CT)scan revealed an obstructive tumor of the
      sigmoid colon with invasion into the bladder. A diverting colostomy was
      performed, and chemotherapy with mFOLFOX6(infusional 5-fluorouracil/Leucovorin+
      oxaliplatin) plus bevacizumab was initiated. The tumor shrunk markedly after 6
      courses of this treatment. Thereafter, laparoscopy- assisted sigmoidectomy was
      successfully performed. Case 2 was a 61-year-old woman admitted with diarrhea,
      abdominal pain, and fever. An abdominal CT scan revealed an obstructive tumor of
      the sigmoid colon with invasion into the ileum, uterus and retroperitoneum. A
      diverting colostomy was performed, and chemotherapy with XELOX(capecitabine+
      oxaliplatin)plus bevacizumab was initiated. The tumor shrunk markedly after 6
      courses of this treatment. Thereafter, laparoscopy- assisted sigmoidectomy was
      successfully performed. Both cases demonstrated partial clinical responses to
      chemotherapy; thus, curative resection surgeries were performed. There were no
      perioperative complications. Therefore, we conclude that oxaliplatin-based
      chemotherapy plus bevacizumab and laparoscopic resection could be very effective
      for locally advanced colon cancer.

PMID- 24743371
TI  - [Combined modality therapy for a patient with primary adrenal lymphoma].
AB  - A 71-year-old man with malaise, anorexia, and weight loss was referred to our
      hospital from a clinic. Abdominal computed tomography(CT)revealed bilateral
      adrenal masses. An ultrasound-guided percutaneous needle biopsy of the adrenal
      grand indicated diffuse large B-cell lymphoma. A rapid adrenocorticotropic
      hormone(ACTH)test revealed primary adrenal failure. Rituximab
      cyclophosphamide/doxorubicin/vincristine/prednisolone(common name, R-CHOP)therapy
      accompanied by intrathecal treatment was initiated along with steroid replacement
      therapy. After the fourth courses, a CT scan showed a reduction of the adrenal
      masses, and there was no[18F]-fluorodeoxyglucose(FDG)uptake in the adrenal
      masses. The patient has remained in metabolic complete remission. Subsequently,
      both adrenal lymphomas were irradiated. The patient has been disease-free for 6
      months after the diagnosis of primary adrenal lymphoma. The combined modality of
      chemoradiation therapy plus intrathecal treatment could be effective for primary
      adrenal lymphoma with a poor prognosis. 

PMID- 24743372
TI  - [Neutropenic enterocolitis after autologous peripheral blood stem cell
      transplantation in non-Hodgkin's lymphoma - a case report].
AB  - Here we report a case of a 59-year-old man who developed neutropenic
      enterocolitis(NE)after autologous peripheral blood stem cell transplantation for
      non-Hodgkin's lymphoma in his second complete remission.Four days after
      transplantation, the patient suffered from diarrhea, abdominal pain, fever, and
      paralytic ileus.Abdominal computerized tomography scan revealed bowel wall
      thickening consistent with NE.Owing to his poor performance status, only medical
      management, including antibiotics and bowel rest, was administered, and the
      patient died 18 days after transplantation.Although NE after autologous
      peripheral blood stem cell transplantation is a relatively rare complication, it
      is important to be aware that this condition can occur as one of the early
      complications in stem cell transplantation. 

PMID- 24743373
TI  - [Prospective study of biotin treatment in patients with erythema due to gefitinib
      or erlotinib].
AB  - Gefitinib anderlotinib, which are epidermal growth factor receptor(EGFR)tyrosine
      kinase inhibitors(TKIs), have been usedfor the treatment of inoperable
      andrecurrent non-small cell lung cancer(NSCLC)patients. These drugs are known to
      cause a skin rash, one of the major side effects, at a high frequency. Biotin is
      a water-soluble vitamin, andit belongs to the vitamin B family. It is well known
      that biotin deficiency increases the risk of skin dermatitis. We administered
      biotin to four patients with skin rash, all of whom were treatedwith either
      gefitinib or erlotinib andwere unable to be treatedby a steroid ointment alone.
      In all patients, administration of biotin reduced the skin rash. Surprisingly, in
      2 patients in whom EGFR-TKI therapy was discontinued because of the skin rash,
      the administration of biotin allowed for long-term gefitinib or erlotinib
      treatment. Biotin may be considereduseful for the treatment of skin rash causedby
      EGFR-TKIs. Further trials may be needed to confirm the value of biotin in this
      setting. 

PMID- 24743374
TI  - [Are the Japanese guidelines for the management of hepatitis B virus reactivation
      being properly implemented ?].
AB  - Hepatitis B virus(HBV)reactivation has been reported as a fatal complication
      following systemic chemotherapy or other immunosuppressive therapies. The
      Japanese Guidelines for HBV reactivation were published in 2009. Despite the
      publication of these guidelines, there have been some reports of fulminant
      hepatitis B. Therefore, it was suggested that the guidelines were not yet been
      widely implemented. We investigated whether the guidelines had been implemented
      in our hospital. After the evaluation, it was determined that 89%of HBV cases
      were screened for the HBV surface antigen(HBs-Ag). Additionally, the screening
      for HBV surface antibody(HBs-Ab)and HBV core antibody(HBc-Ab)should be performed
      in cases negative for HBs-Ag, which was performed in only 17% of HBs-Ag-negative
      cases. It was concluded that the guidelines had not been implemented in our
      hospital. Therefore, we conducted educational activities to promote the
      implementation of the guidelines. Screening tests were performed in all 270 HBV
      cases between January and June 2013. Two antigen-positive carriers were
      identified. The rate of HBs-Ag-negative and/or HBc antibody -positive cases was
      20.3%. Of these, 76.4%were tested using a DNA quantitative test, but DNA
      quantification did not increase in any case. HBV reactivation is expected to
      increase due to the development of new drugs and the use of diverse regimens. All
      physicians who perform immunotherapy and chemotherapy should immediately
      participate in educational activities.

PMID- 24743375
TI  - [Effect of capecitabine therapy on the blood levels of antiepileptic drugs -
      report of two cases].
AB  - We report the cases of 2 breast cancer patients who received capecitabine(CAP)and
      concomitant anticonvulsant therapy with either phenytoin(PHT)or valproate(VPA)for
      brain metastasis. The effect of CAP on the blood levels of the 2 anticonvulsants
      was different and it depended on the variation in metabolism of each drug. Case 1
      involved a 59-year-old woman with recurrent breast cancer. After radiation
      therapy for brain metastases, the patient received PHT(400mg/day)to prevent
      convulsions. After 5 days of PHT administration, CAP therapy was initiated, and
      her blood PHT levels increased to 33.8 mg/mL. Although the PHT dose was reduced
      to 300mg/day, the blood PHT levels markedly increased to 45.5 mg/mL 7 days after
      the withdrawal of CAP. Case 2 involved a 60-year-old woman with breast cancer who
      underwent surgery for brain metastases and subsequently received controlled
      release VPA tablets(400mg/day). No remarkable change was observed in her blood
      VPA levels during CAP treatment or after CAP withdrawal(the blood VAP level after
      7 days of treatment was, 78.4 mg/mL; after 14 days of treatment, 73.2 mg/mL; and
      7 days after withdrawal, 79.7 mg/mL). CAP has been reported to inhibit nucleic
      acid synthesis and/or folic acid activity rather than cytochrome
      P450(CYP)directly. CAP had a significant effect on the blood levels of PHT, which
      is metabolized via the CYP pathway. However, VPA levels remained unchanged
      because VPA metabolism involves other pathways, such as the beta-oxidation and
      conjugation pathways. 

PMID- 24743377
TI  - Primary mesenchymal tumors of the pancreas: single-center experience over 16
      years.
AB  - OBJECTIVE: Primary mesenchymal tumors of the pancreas are extremely rare and no
      comprehensive study of this class of tumors has been previously performed.
      METHODS: Twenty cases of the primary mesenchymal tumors of the pancreas were
      selected and compared clinicopathologic variables with consecutively resected 500
      pancreatic ductal adenocarcinomas. RESULTS: Finally, 20 (0.3%) cases were
      confirmed as primary mesenchymal tumors. The 14 (70%) cases of benign/borderline
      tumors included 4 cases of fibromatoses, 2 cases of cavernous hemangiomas, 2
      cases of schwannomas, 2 cases of solid and cystic hamartomas, 2 cases of solitary
      fibrous tumors, 1 case of inflammatory myofibroblastic tumor, and 1 case of
      angiomyolipoma. The 6 (30%) cases of sarcomas comprised 3 cases of
      undifferentiated/unclassified sarcomas, 1 case of leiomyosarcoma, 1 case of Ewing
      sarcoma/primitive neuroectodermal tumor, and 1 case of atypical lipomatous
      tumor/well-differentiated liposarcoma. When compared with the 500 ductal
      adenocarcinomas, the 3 surgically resected sarcomas were larger (mean, 5.8 cm vs
      3.6 cm; P = 0.02); however, no difference in median survival time was observed
      between patients with sarcoma (23 months) and patients with ductal adenocarcinoma
      (16 months). CONCLUSIONS: First, primary mesenchymal tumors of the pancreas are
      extremely rare. Second, several primary mesenchymal tumor types can be observed
      in the pancreas. Understanding these rare disease entities will help ensure their
      correct diagnosis.

PMID- 24743376
TI  - Effects of the trace amine-associated receptor 1 agonist RO5263397 on abuse
      related effects of cocaine in rats.
AB  - Animal knockout studies suggest that trace amine-associated receptor (TAAR) 1 is
      involved in behavioral effects of psychostimulants such as cocaine. Recently,
      several highly selective TAAR 1 agonists have been discovered. However, little is
      known of the impact of TAAR 1 agonists on abuse-related effects of cocaine. Here,
      we report the effects of a TAAR 1 agonist RO5263397 on several abuse-related
      behavioral effects of cocaine in rats. RO5263397 was evaluated for its effects on
      cocaine-induced behavioral sensitization, conditioned place preference (CPP), cue
      and cocaine prime-induced reinstatement of cocaine-seeking behavior, and cocaine
      self-administration using behavioral economic analysis. RO5263397 reduced the
      expression of cocaine behavioral sensitization, cue- and cocaine prime-induced
      reinstatement of cocaine seeking, and expression but not development of cocaine
      CPP. Behavioral economic analysis showed that RO5263397 increased the elasticity
      of the cocaine demand curve, but did not change cocaine consumption at minimal
      prices. Taken together, this is the first systematic assessment of a TAAR 1
      agonist on a range of behavioral effects of cocaine, showing that RO5263397 was
      efficacious in reducing cocaine-mediated behaviors. Collectively, these data
      uncover essential neuromodulatory roles of TAAR 1 on cocaine abuse, and suggest
      that TAAR 1 may represent a novel drug target for the treatment of cocaine
      addiction. 

PMID- 24743378
TI  - Does a family history of pancreatic ductal adenocarcinoma and cyst size influence
      the follow-up strategy for intraductal papillary mucinous neoplasms of the
      pancreas?
AB  - OBJECTIVE: This study aimed to evaluate the relationship between pancreatic
      ductal adenocarcinoma (PDAC) family history and PDAC development in patients
      followed up for intraductal papillary mucinous neoplasms (IPMNs) and to assess
      the cyst size relevance in determining follow-up strategies. METHODS: We analyzed
      300 patients with branch duct and mixed-type IPMN who were followed up at our
      facility. RESULTS: Among the patients aged 70 years or older, the frequency of
      PDAC did not differ significantly between those with 1 first-degree relative with
      PDAC and those without a family history. Although patients with IPMNs of greater
      than or equal to 30 mm were followed up for a significantly shorter duration than
      those patients with IPMNs of less than 30 mm, the frequency of IPMN progression
      and malignant IPMN was significantly greater in the former. The frequency of IPMN
      progression and pancreatic cancer did not differ significantly according to IPMN
      size (<10, 10-20, and 20-30 mm) in cases without mural nodules. CONCLUSIONS:
      Patients with 1 first-degree relative with PDAC can be followed up using the same
      criteria for patients without a family history. Special attention should be paid
      to IPMN progression and malignant transformation in patients with IPMNs of
      greater than or equal to 30 mm, but cyst size need not be considered when
      determining follow-up strategies for patients with IPMNs of less than 30 mm
      without mural nodules.

PMID- 24743379
TI  - Quality of life and functional outcome after resection of pancreatic cystic
      neoplasm.
AB  - OBJECTIVES: The objectives of this study were to assess the long-term quality of
      life (QOL) after the resection of a primary pancreatic cyst and to determine
      predictors of outcome. Secondary outcomes were pancreatic function and survival.
      METHODS: One hundred eight consecutive patients, who underwent resection between
      1992 and 2007 and had nearly 60 months follow-up, were reviewed. Questionnaires
      and function tests were collected during scheduled outpatient clinic visits.
      RESULTS: At follow-up, 20 patients had died. Five-year overall survival was 94%
      for benign and 62% for malignant neoplasia. Of 88 living patients, 65 (74%)
      returned questionnaires. Generic physical and mental QOL scores were equal or
      better compared with healthy references. None of the disease-specific symptom
      scales were above mean 50, implicating none to mild complaints. Independent
      predictors for good generic QOL were young age (P < 0.05) and resected malignancy
      (P < 0.05); predictors for good gastrointestinal QOL were male sex (P < 0.1),
      limited resection (P < 0.05), endocrine insufficiency (P < 0.05), and employment
      (P < 0.05). Endocrine insufficiency prevalence was 40%, and 59% for exocrine
      insufficiency. CONCLUSIONS: After cyst resection, long-term QOL is equal to
      healthy references, pancreatic insufficiency is prevalent but does not impair
      QOL, and survival relates positive compared with solid pancreatic adenocarcinoma.
      The excellent long-term outcome justifies proceeding with surgery once a medical
      indication for resection has been established.

PMID- 24743380
TI  - A 5-year experience of benign pancreatic hyperenzymemia.
AB  - OBJECTIVE: Benign pancreatic hyperenzymemia is characterized by a long-term
      increase of serum pancreatic enzymes in otherwise healthy subjects. This study
      was designed to determine (a) whether all pancreatic enzymes are elevated, (b)
      the extent of each enzyme increase, (c) the relative frequency of the familial
      form, and (d) the relative frequencies of pancreatic and salivary hyperamylasemia
      and macroamylasemia. METHODS: Two hundred seven asymptomatic subjects with benign
      pancreatic hyperenzymemia were studied during the 5-year period. Serum amylase,
      isoamylase, and lipase levels were assessed by immunoenzymatic assays. RESULTS:
      Most (n = 183; 88.4%) patients had benign pancreatic hyperenzymemia; 155 (74.9%)
      patients had an abnormal increase of all 3 enzymes, 15 (7.2%) patients of only
      lipase, and 13 (6.3%) patients of only amylase and pancreatic isoamylase. Lipase
      levels were the highest (1.1-21 times above upper limit). Of the 183 subjects, 72
      were members of 35 different families, 15 (7.2%) had increased salivary amylase,
      and 9 (4.3%) had macroamylasemia. Wide day-to-day fluctuations of pancreatic
      enzymes, including falls within the reference ranges, were recorded. CONCLUSIONS:
      All enzymes were increased in benign pancreatic hyperenzymemia, with lipase
      showing the highest elevation. Doctors should reassure patients about the benign
      nature of this condition and limit repeating useless examinations.

PMID- 24743381
TI  - Magnetic resonance cholangiopancreatography in the diagnosis of pancreas divisum:
      a systematic review and meta-analysis.
AB  - OBJECTIVE: This study aimed to perform a structured meta-analysis of all eligible
      studies to assess the overall diagnostic use of magnetic resonance
      cholangiopancreatography (MRCP) alone or with secretin enhancement (secretin
      enhanced MRCP [S-MRCP]) in the detection of pancreas divisum. METHODS: Two
      authors independently performed a comprehensive search of PubMed, MEDLINE, and
      the Cochrane Library from inception to September 2013. Studies were included if
      they allowed construction of 2 * 2 contingency tables of MRCP and/or S-MRCP
      compared with criterion standard. DerSimonian-Laird random effect models were
      used to estimate the pooled sensitivity, specificity, specificity, and
      quantitative receiver operating characteristics. RESULTS: Of 51 citations, 10
      studies with 1474 patients were included. Secretin-enhanced MRCP had a higher
      overall diagnostic performance than MRCP (S-MRCP: pooled sensitivity, 86% [95%
      confidence interval (CI), 77%-93%]; specificity, 97% [95% CI, 94%-99%]; and area
      under the curve, 0.93 +/- 0.056 compared with MRCP: sensitivity, 52% [95% CI, 45%
      59%]; specificity, 97% [95% CI, 94%-99%]; and area under the curve, 0.76 +/-
      0.104). Pooled diagnostic odds ratios were 72.19 (95% CI, 5.66-938.8) and 23.39
      (95% CI, 7.93-69.02) for S-MRCP and MRCP, respectively. Visual inspection of the
      funnel plot showed low potential for publication bias. CONCLUSIONS: Secretin
      enhanced MRCP has a much higher diagnostic accuracy than MRCP and should be
      preferred for diagnosis of pancreas divisum.

PMID- 24743383
TI  - Vascular skeletalization ---- a new concept to improve the resection rate in
      childhood neuroblastoma.
AB  - AIM: The surgical resection rate in childhood neuroblastoma (Stage III and IV) is
      relatively low and influences the prognosis greatly. This study analyzes the
      surgical resection rate of stage I neuroblastoma in children. METHODS: The tumors
      are shrunk with preoperative chemotherapy and surgical resection in the iliac
      vessels is performed to skeletalize the large retroperitoneal vascular. Using
      this method, 22 cases of childhood neuroblastoma received resections and the
      outcomes were analyzed. RESULTS: The tumors were completely removed in 21 out of
      the 22 cases (95.45% in total). There were no serious complications and
      perioperative deaths. CONCLUSIONS: Using proper surgical methods and
      skeletalizing the large retroperitoneal vessels significantly increases the
      resection rate.

PMID- 24743382
TI  - Cloning and characterization of the human trefoil factor 3 gene promoter.
AB  - Human trefoil factor 3 (hTFF3) is a small-molecule peptide with potential
      medicinal value. Its main pharmacological function is to alleviate
      gastrointestinal mucosal injuries caused by various factors and promote the
      repair of damaged mucosa. However, how its transcription is regulated is not yet
      known. The aim of this study was to clone the hTFF3 gene promoter region,
      identify the core promoter and any transcription factors that bind to the
      promoter, and begin to clarify the regulation of its expression. The 5' flanking
      sequence of the hTFF3 gene was cloned from human whole blood genomic DNA by PCR.
      Truncated promoter fragments with different were cloned and inserted into the
      pGL3-Basic vector to determine the position of the core hTFF3 promoter.
      Transcription element maintaining basic transcriptional activity was assessed by
      mutation techniques. Protein-DNA interactions were analyzed by chromatin
      immunoprecipitation (ChIP). RNA interference and gene over-expression were
      performed to assay the effect of transcription factor on the hTFF3 expression.
      The results showed that approximately 1,826 bp of the fragment upstream of hTFF3
      was successfully amplified, and its core promoter region was determined to be
      from -300 bp to -280 bp through analysis of truncated mutants. Mutation analysis
      confirmed that the sequence required to maintain basic transcriptional activity
      was accurately positioned from -300 bp to -296 bp. Bioinformatic analysis
      indicated that this area contained a Sp1 binding site. Sp1 binding to the hTFF3
      promoter was confirmed by ChIP experiments. Sp1 over-expression and interference
      experiments showed that Sp1 enhanced the transcriptional activity of the hTFF3
      promoter and increased hTFF3 expression. This study demonstrated that Sp1 plays
      an important role in maintaining the transcription of hTFF3.

PMID- 24743385
TI  - Differentiation of the intracellular structure of slow- versus fast-twitch muscle
      fibers through evaluation of the dielectric properties of tissue.
AB  - Slow-twitch (type 1) skeletal muscle fibers have markedly greater mitochondrial
      content than fast-twitch (type 2) fibers. Accordingly, we sought to determine
      whether the dielectric properties of these two fiber types differed, consistent
      with their distinct intracellular morphologies. The longitudinal and transverse
      dielectric spectrum of the ex vivo rat soleus (a predominantly type 1 muscle) and
      the superficial layers of rat gastrocnemius (predominantly type 2) (n = 15) were
      measured in the 1 kHz-10 MHz frequency range and modeled to a resistivity Cole
      Cole function. Major differences were especially apparent in the dielectric
      spectrum in the 1 to 10 MHz range. Specifically, the gastrocnemius demonstrated a
      well-defined, higher center frequency than the soleus muscle, whereas the soleus
      muscle showed a greater difference in the modeled zero and infinite resistivities
      than the gastrocnemius. These findings are consistent with the fact that soleus
      tissue has larger and more numerous mitochondria than gastrocnemius. Evaluation
      of tissue at high frequency could provide a novel approach for assessing
      intracellular structure in health and disease. 

PMID- 24743384
TI  - The MLH1 c.1852_1853delinsGC (p.K618A) variant in colorectal cancer: genetic
      association study in 18,723 individuals.
AB  - Colorectal cancer is one of the most frequent neoplasms and an important cause of
      mortality in the developed world. Mendelian syndromes account for about 5% of the
      total burden of CRC, being Lynch syndrome and familial adenomatous polyposis the
      most common forms. Lynch syndrome tumors develop mainly as a consequence of
      defective DNA mismatch repair associated with germline mutations in MLH1, MSH2,
      MSH6 and PMS2. A significant proportion of variants identified by screening these
      genes correspond to missense or noncoding changes without a clear pathogenic
      consequence, and they are designated as "variants of uncertain significance",
      being the c.1852_1853delinsGC (p.K618A) variant in the MLH1 gene a clear example.
      The implication of this variant as a low-penetrance risk variant for CRC was
      assessed in the present study by performing a case-control study within a large
      cohort from the COGENT consortium-COST Action BM1206 including 18,723 individuals
      (8,055 colorectal cancer cases and 10,668 controls) and a case-only genotype
      phenotype correlation with several clinical and pathological characteristics
      restricted to the Epicolon cohort. Our results showed no involvement of this
      variant as a low-penetrance variant for colorectal cancer genetic susceptibility
      and no association with any clinical and pathological characteristics including
      family history for this neoplasm or Lynch syndrome. 

PMID- 24743386
TI  - Transcription-associated R-loop formation across the human FMR1 CGG-repeat
      region.
AB  - Expansion of a trinucleotide (CGG) repeat element within the 5' untranslated
      region (5'UTR) of the human FMR1 gene is responsible for a number of heritable
      disorders operating through distinct pathogenic mechanisms: gene silencing for
      fragile X syndrome (>200 CGG) and RNA toxic gain-of-function for FXTAS (~ 55-200
      CGG). Existing models have focused almost exclusively on post-transcriptional
      mechanisms, but co-transcriptional processes could also contribute to the
      molecular dysfunction of FMR1. We have observed that transcription through the GC
      rich FMR1 5'UTR region favors R-loop formation, with the nascent (G-rich) RNA
      forming a stable RNA:DNA hybrid with the template DNA strand, thereby displacing
      the non-template DNA strand. Using DNA:RNA (hybrid) immunoprecipitation (DRIP) of
      genomic DNA from cultured human dermal fibroblasts with both normal (~ 30 CGG
      repeats) and premutation (55<CGG<200 repeats) alleles, we provide evidence for
      FMR1 R-loop formation in human genomic DNA. Using a doxycycline (DOX)-inducible
      episomal system in which both the CGG-repeat and transcription frequency can be
      varied, we further show that R-loop formation increases with higher expression
      levels. Finally, non-denaturing bisulfite mapping of the displaced single
      stranded DNA confirmed R-loop formation at the endogenous FMR1 locus and further
      indicated that R-loops formed over CGG repeats may be prone to structural
      complexities, including hairpin formation, not commonly associated with other R
      loops. These observations introduce a new molecular feature of the FMR1 gene that
      is directly affected by CGG-repeat expansion and is likely to be involved in the
      associated cellular dysfunction.

PMID- 24743387
TI  - Active learning to understand infectious disease models and improve policy
      making.
AB  - Modeling plays a major role in policy making, especially for infectious disease
      interventions but such models can be complex and computationally intensive. A
      more systematic exploration is needed to gain a thorough systems understanding.
      We present an active learning approach based on machine learning techniques as
      iterative surrogate modeling and model-guided experimentation to systematically
      analyze both common and edge manifestations of complex model runs. Symbolic
      regression is used for nonlinear response surface modeling with automatic feature
      selection. First, we illustrate our approach using an individual-based model for
      influenza vaccination. After optimizing the parameter space, we observe an
      inverse relationship between vaccination coverage and cumulative attack rate
      reinforced by herd immunity. Second, we demonstrate the use of surrogate modeling
      techniques on input-response data from a deterministic dynamic model, which was
      designed to explore the cost-effectiveness of varicella-zoster virus vaccination.
      We use symbolic regression to handle high dimensionality and correlated inputs
      and to identify the most influential variables. Provided insight is used to focus
      research, reduce dimensionality and decrease decision uncertainty. We conclude
      that active learning is needed to fully understand complex systems behavior.
      Surrogate models can be readily explored at no computational expense, and can
      also be used as emulator to improve rapid policy making in various settings. 

PMID- 24743388
TI  - Hospitalisations for pelvic inflammatory disease temporally related to a
      diagnosis of Chlamydia or gonorrhoea: a retrospective cohort study.
AB  - OBJECTIVES: The presence and severity of pelvic inflammatory disease (PID)
      symptoms are thought to vary by microbiological etiology but there is limited
      empirical evidence. We sought to estimate and compare the rates of
      hospitalisation for PID temporally related to diagnoses of gonorrhoea and
      chlamydia. METHODS: All women, aged 15-45 years in the Australian state of New
      South Wales (NSW), with a diagnosis of chlamydia or gonorrhoea between 01/07/2000
      and 31/12/2008 were followed by record linkage for up to one year after their
      chlamydia or gonorrhoea diagnosis for hospitalisations for PID. Standardised
      incidence ratios compared the incidence of PID hospitalisations to the age
      equivalent NSW population. RESULTS: A total of 38,193 women had a chlamydia
      diagnosis, of which 483 were hospitalised for PID; incidence rate (IR) 13.9 per
      1000 person-years of follow-up (PYFU) (95%CI 12.6-15.1). In contrast, 1015 had a
      gonorrhoea diagnosis, of which 45 were hospitalised for PID (IR 50.8 per 1000
      PYFU, 95%CI 36.0-65.6). The annual incidence of PID hospitalisation temporally
      related to a chlamydia or gonorrhoea diagnosis was 27.0 (95%CI 24.4-29.8) and
      96.6 (95%CI 64.7-138.8) times greater, respectively, than the age-equivalent NSW
      female population. Younger age, socio-economic disadvantage, having a diagnosis
      prior to 2005 and having a prior birth were also associated with being
      hospitalised for PID. CONCLUSIONS: Chlamydia and gonorrhoea are both associated
      with large increases in the risk of PID hospitalisation. Our data suggest the
      risk of PID hospitalisation is much higher for gonorrhoea than chlamydia;
      however, further research is needed to confirm this finding.

PMID- 24743390
TI  - A review of the evidence for the use of ventilation as a surrogate measure of
      energy expenditure.
AB  - Precise measurement of sedentary behavior and physical activity is necessary to
      characterize the dose-response relationship between these variables and health
      outcomes. The most frequently used methods employ portable devices to measure
      mechanical or physiological parameters (eg, pedometers, heart rate monitors,
      accelerometers). There is considerable variability in the accuracy of total
      energy expenditure (TEE) estimates from these devices. This review examines the
      potential of measurement of ventilation (VE) to provide an estimate of free
      living TEE. The existence of a linear relationship between VE and energy
      expenditure (EE) was demonstrated in the mid-20th century. However, few studies
      have investigated this parameter as an estimate of EE due to the cumbersome
      equipment required to measure VE. Portable systems that measure VE without the
      use of a mouthpiece have existed for about 20 years (respiratory inductive
      plethysmography). However, these devices are adapted for clinical monitoring and
      are too cumbersome to be used in conditions of daily life. Technological
      innovations of recent years (small electromagnetic coils glued on the chest/back)
      suggest that VE could be estimated from variations in rib cage and abdominal
      distances. This method of TEE estimation is based on the development of
      individual/group calibration curves to predict the relationship between
      ventilation and oxygen consumption. The new method provides a reasonably accurate
      estimate of TEE in different free-living conditions such as sitting, standing,
      and walking. Further work is required to integrate these electromagnetic coils
      into a jacket or T-shirt to create a wearable device suitable for long-term use
      in free-living conditions.

PMID- 24743389
TI  - Diagnostic performance of Schistosoma real-time PCR in urine samples from Kenyan
      children infected with Schistosoma haematobium: day-to-day variation and follow
      up after praziquantel treatment.
AB  - BACKGROUND: In an effort to enhance accuracy of diagnosis of Schistosoma
      haematobium, this study explores day-to-day variability and diagnostic
      performance of real-time PCR for detection and quantification of Schistosoma DNA
      compared to other diagnostic tools in an endemic area before and after treatment.
      METHODOLOGY: Previously collected urine samples (N = 390) from 114 preselected
      proven parasitological and/or clinical S. haematobium positive Kenyan
      schoolchildren were analyzed by a Schistosoma internal transcribed spacer-based
      real-time PCR after 14 years of storage. Pre-treatment day-to-day fluctuations of
      PCR and microscopy over three consecutive days were measured for 24 children
      using intra-class correlation coefficient. A combined 'gold standard' (PCR and/or
      microscopy positive) was used to measure sensitivity and negative predictive
      value (NPV) of several diagnostic tools at baseline, two and 18 months post
      treatment with praziquantel. PRINCIPAL FINDINGS: All 24 repeatedly tested
      children were PCR-positive over three days with little daily variation in median
      Ct-values, while 83.3% were found to be egg-positive for S. haematobium at day 1
      and 75.0% at day 2 and 3 pre-treatment, signifying daily fluctuations in
      microscopy diagnosis. Of all 114 preselected schoolchildren, repeated microscopic
      measurements were required to detect 96.5% versus 100% of positive pre-treatment
      cases by single PCR. At two months post-treatment, microscopy and PCR detected
      22.8% versus 69.3% positive children, respectively. Based on the 'gold standard',
      PCR showed high sensitivity (>92%) as compared to >31% sensitivity for
      microscopy, both pre- and post-treatment. CONCLUSIONS/SIGNIFICANCE: Detection and
      quantification of Schistosoma DNA in urine by real-time PCR was shown to be a
      powerful and specific diagnostic tool for detection of S. haematobium infections,
      with less day-to-day variation and higher sensitivity compared to microscopy. The
      superior performance of PCR before, and two and 18 months post-treatment provides
      a compelling argument for PCR as an accurate and reproducible tool for monitoring
      treatment efficacy.

PMID- 24743391
TI  - Plasma Aluminum Concentrations in Pediatric Patients Receiving Long-Term
      Parenteral Nutrition.
AB  - BACKGROUND: Patients receiving long-term parenteral nutrition (PN) are at
      increased risk of aluminium (Al) toxicity because of bypass of the
      gastrointestinal tract during PN infusion. Complications of Al toxicity include
      metabolic bone disease (MBD), Al-associated encephalopathy in adults, and
      impaired neurological development in preterm infants. Unlike the United States,
      there are no regulations regarding Al content of large- and small-volume
      parenterals in Canada. We, therefore, aimed to present our data on plasma Al
      concentration and Al intake from our cohort of pediatric patients receiving long
      term PN. METHODS: Plasma Al concentration was retrospectively gathered from the
      patient charts of all 27 patients with intestinal failure (IF) receiving long
      term PN at The Hospital for Sick Children, Toronto, Canada, and compared with age
      and sex-matched controls recruited for comparison. In addition, Al concentration
      was measured in PN samples collected from 10 randomly selected patients with IF
      and used to determine their Al intake. RESULTS: The plasma Al concentration of
      patients with IF receiving long-term PN was significantly higher than that of
      control participants (1195 +/- 710 vs 142 +/- 63 nmol/L; P < .0001). In the
      subgroup of 10 patients for whom Al intake from their PN solution was determined,
      mean +/- SD Al intake from PN was 15.4 +/- 15 ug/kg, 3 times the Food and Drug
      Administration upper recommended intake level, and Al intake was significantly
      related to plasma Al concentration (P = .02, r (2) = 0.52). CONCLUSION: Pediatric
      patients receiving long-term PN for IF in Canada are at risk for Al toxicity.

PMID- 24743392
TI  - Regulator of G protein signaling 2 (RGS2) and RGS4 form distinct G protein
      dependent complexes with protease activated-receptor 1 (PAR1) in live cells.
AB  - Protease-activated receptor 1 (PAR1) is a G-protein coupled receptor (GPCR) that
      is activated by natural proteases to regulate many physiological actions. We
      previously reported that PAR1 couples to Gi, Gq and G12 to activate linked
      signaling pathways. Regulators of G protein signaling (RGS) proteins serve as
      GTPase activating proteins to inhibit GPCR/G protein signaling. Some RGS proteins
      interact directly with certain GPCRs to modulate their signals, though cellular
      mechanisms dictating selective RGS/GPCR coupling are poorly understood. Here,
      using bioluminescence resonance energy transfer (BRET), we tested whether RGS2
      and RGS4 bind to PAR1 in live COS-7 cells to regulate PAR1/Galpha-mediated
      signaling. We report that PAR1 selectively interacts with either RGS2 or RGS4 in
      a G protein-dependent manner. Very little BRET activity is observed between PAR1
      Venus (PAR1-Ven) and either RGS2-Luciferase (RGS2-Luc) or RGS4-Luc in the absence
      of Galpha. However, in the presence of specific Galpha subunits, BRET activity
      was markedly enhanced between PAR1-RGS2 by Galphaq/11, and PAR1-RGS4 by Galphao,
      but not by other Galpha subunits. Galphaq/11-YFP/RGS2-Luc BRET activity is
      promoted by PAR1 and is markedly enhanced by agonist (TFLLR) stimulation.
      However, PAR1-Ven/RGS-Luc BRET activity was blocked by a PAR1 mutant (R205A) that
      eliminates PAR1-Gq/11 coupling. The purified intracellular third loop of PAR1
      binds directly to purified His-RGS2 or His-RGS4. In cells, RGS2 and RGS4
      inhibited PAR1/Galpha-mediated calcium and MAPK/ERK signaling, respectively, but
      not RhoA signaling. Our findings indicate that RGS2 and RGS4 interact directly
      with PAR1 in Galpha-dependent manner to modulate PAR1/Galpha-mediated signaling,
      and highlight a cellular mechanism for selective GPCR/G protein/RGS coupling.

PMID- 24743393
TI  - Cross-sectional and longitudinal relation of IGF1 and IGF-binding protein 3 with
      lipid metabolism.
AB  - BACKGROUND: Previous intervention studies in patients with GH disorders suggested
      an impact of IGF1 and IGF-binding protein 3 (IGFBP3) on lipid metabolism, whereas
      population-based studies revealed conflicting results. Therefore, we aimed to
      assess the cross-sectional and longitudinal associations between IGF1 or IGFBP3
      serum levels and lipids (total, LDL, or HDL cholesterol and triglycerides) in a
      large-scale study. METHODS: Data of 2935 subjects (1356 women) from the
      population-based Study of Health in Pomerania (SHIP) were used. ANOVA, quantile
      regression, and logistic regression models adjusted for age, waist circumference,
      physical activity, and alcohol consumption were performed. RESULTS: In cross
      sectional analyses, we detected that IGF1 and IGFBP3 levels were positively
      related to total and LDL cholesterol and inversely related to HDL cholesterol in
      both sexes. Furthermore, IGFBP3 levels showed a positive relationship to
      triglycerides. In total, IGFBP3 levels were more strongly associated to lipids
      than IGF1. In longitudinal analysis, we found no influence of baseline IGF1 or
      IGFBP3 serum concentration on incidentally elevated or reduced lipid levels.
      However, the positive relationship between IGFBP3 and incidentally elevated
      triglycerides barely missed statistical significance in women. CONCLUSION: The
      present study showed strong cross-sectional associations between IGF1 or IGFBP3
      and lipids, whereas no longitudinal relationships were revealed. Therefore, our
      findings suggest IGF1 and IGFBP3 as a risk marker rather than a risk factor for
      alterations in lipid metabolism. Further studies are needed to elucidate the
      mechanisms underlying the association between the GH/IGF axis and lipid
      metabolism.

PMID- 24743394
TI  - Telomere length analysis in Cushing's syndrome.
AB  - INTRODUCTION: Hypercortisolism in Cushing's syndrome (CS) is associated with
      increased morbidity and mortality. Hypercortisolism also occurs in chronic
      depressive disorders and stress, where telomere length (TL) is shorter than in
      controls. We hypothesized that shortening of telomere might occur in CS and
      contribute to premature aging and morbidity. AIM: To investigate TL in CS
      patients compared with controls. METHODS: Seventy-seven CS patients (14 males, 59
      pituitary, 17 adrenal, and one ectopic; 21 with active disease) were compared
      with 77 gender-, age-, and smoking-matched controls. Fifteen CS were evaluated
      longitudinally, during active disease and after remission of hypercortisolism.
      Leukocyte TL was measured by telomere restriction fragment-Southern technique.
      Clinical markers were included in a multiple linear regression analysis to
      investigate potential predictors of TL. RESULTS: Mean TL in CS patients and
      controls was similar (7667 vs 7483 bp, NS). After adjustment for age, in the
      longitudinal evaluation, TL was shorter in active disease than after remission
      (7273 vs 7870, P<0.05). Age and dyslipidemia were negative predictors (P<0.05),
      and total leukocyte count was a positive predictor for TL (P<0.05). As expected,
      a negative correlation was found between TL and age (CS, R=-0.400 and controls,
      R=-0.292; P<0.05). No correlation was found between circulating cortisol,
      duration of exposure to hypercortisolism or biochemical cure and TL. CONCLUSION:
      Even though in the cross-sectional comparison of CS and controls no difference in
      TL was found, in the longitudinal evaluation, patients with active CS had shorter
      TL than after biochemical cure of hypercortisolism. These preliminary results
      suggest that hypercortisolism might negatively impact telomere maintenance.
      Larger studies are needed to confirm these findings.

PMID- 24743395
TI  - Serum negative autoimmune thyroiditis displays a milder clinical picture compared
      with classic Hashimoto's thyroiditis.
AB  - BACKGROUND: Despite high sensitivity of current assays for autoantibodies to
      thyroperoxidase (TPO) and to thyroglobulin (Tg), some hypothyroid patients still
      present with negative tests for circulating anti-thyroid Abs. These patients
      usually referred to as having seronegative autoimmune thyroiditis (seronegative
      CAT) have not been characterized, and definite proof that their clinical
      phenotype is similar to that of patients with classic chronic autoimmune
      thyroiditis (CAT) is lacking. OBJECTIVE: To compare the clinical phenotype of
      seronegative CAT (SN-CAT) and CAT as diagnosed according to a raised serum level
      of TSH with negative and positive tests for anti-thyroid Abs respectively.
      METHODS: A case-control retrospective study enrolling 55 patients with SN-CAT and
      110 patients with CAT was performed. Serum free triiodothyronine (FT3), free
      thyroxine (FT4), TSH, Tg Abs, and TPO Abs were measured in all patients. RESULTS:
      Patients with SN-CAT displayed significantly lower mean levels of TSH (6.6+/-3.4
      vs 10.2+/-9.8 MUU/ml; P=0.009), higher mean FT4 levels (1.1+/-0.2 vs 0.9+/-0.2
      ng/dl; P=0.0002), and similar FT3 levels when compared with CAT patients. Mean
      thyroid volume was significantly greater in patients with CAT when compared with
      SN-CAT patients (11.2+/-6.5 vs 8.1+/-3.7 ml; P=0.001). Logistic regression
      demonstrated that FT4 (0.123 (0.019-0.775); (P=0.026)) and thyroid volume (1.243
      (1.108-1.394); (P=0.0002)) were significantly and independently related to the
      diagnosis (CAT/SN-CAT). Patients with SN-CAT had a similar prevalence of thyroid
      nodules and female gender but a lower prevalence of overt hypothyroidism (5.4 vs
      20.9%; P=0.012) as opposed to patients with CAT. CONCLUSIONS: These results
      suggest an autoimmune etiology of SN-CAT, which, however, seems to have a milder
      clinical course when compared with CAT.

PMID- 24743396
TI  - Bilateral adrenal incidentalomas differ from unilateral adrenal incidentalomas in
      subclinical cortisol hypersecretion but not in potential clinical implications.
AB  - OBJECTIVE: To investigate the possibility of a different prevalence of
      subclinical Cushing's syndrome (SCS) and potentially related morbidities between
      patients with unilateral adrenal incidentalomas (UAI) and bilateral adrenal
      incidentalomas (BAI), as existing data are few and controversial. DESIGN:
      Prospective observational study. METHODS: Clinical examination, biochemical
      tests, and hormonal evaluation were performed in 298 consecutive patients with
      adrenal incidentalomas, unilateral in 224 patients (75.2%), bilateral in 74
      patients (24.8%), with apparently benign masses based on imaging characteristics
      and after exclusion of overt endocrine disease. The diagnosis of SCS was based on
      a post-dexamethasone suppression test (2 mg dexamethasone/24 h for 48 h), with
      serum cortisol level >=1.8 MUg/dl combined with at least one abnormal result of
      the other hormonal measurements. RESULTS: SCS was diagnosed in 66 out of 298
      (22.1%) patients, being more frequent in patients with BAI (35.1 vs 17.9%,
      P=0.003, for BAI and UAI respectively). Hypertension, type 2 diabetes mellitus,
      impaired glucose tolerance, and dyslipidemia were of a similar frequency in both
      groups. SCS patients with UAI and BAI did not differ in age, gender, BMI, waist
      circumference, and mass size. Factors related to SCS were the presence of BAI
      (OR, 3.24; 95% CI, 2.31-4.54) and mass size (OR, 2.63; 95% CI, 1.31-5.26).
      CONCLUSION: BAI patients present more often with SCS when compared with UAI
      patients; however, morbidities potentially related to subtle cortisol
      hypersecretion were of a similar frequency in both groups. Further studies are
      needed to clarify whether this difference in hormonal activity may be related to
      different pathophysiologies.

PMID- 24743397
TI  - Tissue-specific dysregulation of 11beta-hydroxysteroid dehydrogenase type 1 in
      overweight/obese women with polycystic ovary syndrome compared with weight
      matched controls.
AB  - CONTEXT: Abnormal cortisol metabolism in polycystic ovary syndrome (PCOS) has
      been invoked as a cause of secondary activation of the hypothalamic-pituitary
      adrenal axis and hence androgen excess. However, this is based on urinary
      excretion of cortisol metabolites, which cannot detect tissue-specific changes in
      metabolism and may be confounded by obesity. OBJECTIVE: To assess cortisol
      clearance and whole-body and tissue-specific activities of 11beta-hydroxysteroid
      dehydrogenase type 1 (11beta-HSD1 (HSD11B1)) in PCOS. DESIGN: Case-control study.
      SETTING: Medical center. PATIENTS: A total of 20 overweight-obese unmedicated
      Caucasian women with PCOS, aged 18-45 years, and 20 Caucasian controls matched
      for age, BMI, body fat distribution, and HSD11B1 genotypes (rs846910 and
      rs12086634). MAIN OUTCOME MEASURES: Cortisol metabolites were measured in 24 h
      urine. During steady-state 9,11,12,12-[(2)H]4-cortisol infusion, cortisol
      clearance was calculated and whole-body HSD11B1 activity was assessed as the rate
      of appearance of 9,12,12-(2)H3-cortisol (d3-cortisol). Hepatic HSD11B1 activity
      was quantified as the generation of plasma cortisol following an oral dose of
      cortisone. Subcutaneous adipose HSD11B1 activity and HSD11B1 mRNA were measured,
      ex vivo, in biopsies. RESULTS: Urinary cortisol metabolite excretion, deuterated
      cortisol clearance, and the rate of appearance of d3-cortisol did not differ
      between patients with PCOS and controls. However, hepatic HSD11B1 conversion of
      oral cortisone to cortisol was impaired (P<0.05), whereas subcutaneous abdominal
      adipose tissue HSD11B1 mRNA levels and activity were increased (P<0.05) in women
      with PCOS when compared with controls. CONCLUSIONS: Tissue-specific dysregulation
      of HSD11B1 is a feature of PCOS, over and above obesity, whereas increased
      clearance of cortisol may result from obesity rather than PCOS.

PMID- 24743398
TI  - Pregnancy outcomes in women with primary hyperparathyroidism.
AB  - OBJECTIVE: To study pregnancy and pregnancy outcomes in women with primary
      hyperparathyroidism (PHPT) and in controls. DESIGN: Register-based retrospective
      cohort study of women aged 16-44 years with a diagnosis of PHPT with age- and
      gender-matched non-exposed controls in Denmark. METHODS: The patients and
      controls were identified using the Danish National Hospital Discharge Register
      for the period 1977-2010. The outcomes were determined using the Birth Register,
      the Abortion Register and the LPR (National Hospital Discharge Register). The
      primary outcome was the relative risk of abortions in patients compared with
      controls. RESULTS: A total of 1057 women with PHPT and 3171 controls were
      identified. The number of women giving birth and experiencing abortions did not
      differ between the two groups (live births, P=0.21 and abortions, P=0.12). Also
      birth weight, length, Apgar score, and gestation length at abortion did not
      differ. Within the first year after the diagnosis was made, gestation length was
      lower in women with PHPT than that in controls. However, this was linked to more
      deliveries by caesarian sections. CONCLUSIONS: A diagnosis of PHPT did not seem
      to increase the rate of abortions in our study. Reducing the abortion risk may
      therefore not be an indication for parathyroidectomy during pregnancy in patients
      with mild PHPT. The PHPT diagnosis does not seem to affect birth weight, length
      and Apgar score. The higher number of deliveries by cesarean section after the
      diagnosis was made may be associated with lower gestation age. The strategy for
      delivery should be carefully considered in pregnant women with PHPT.

PMID- 24743399
TI  - Refractory hypercalcaemia secondary to parathyroid carcinoma: response to high
      dose denosumab.
AB  - OBJECTIVE: Hypercalcaemia is an important cause of increased morbidity and
      mortality in patients with parathyroid carcinoma. Surgical resection is the
      mainstay of treatment but, equally, managing hypercalcaemia is of paramount
      importance. At present, few therapies have been shown to be effective in the most
      severe cases. This report describes the efficacy of denosumab in a patient with
      parathyroid carcinoma when conventional therapies had been shown to be relatively
      ineffective.SUBJECT, METHODS AND RESULTS: A 50-year-old man presented with
      symptomatic hypercalcaemia 1 year after the surgery for his parathyroid
      carcinoma. Investigations revealed raised serum calcium and parathyroid hormone
      concentrations consistent with the recurrence of the disease. Imaging failed to
      localise any surgically remediable foci. Medical management with loop diuretics,
      calcimimetics and bisphosphonates failed to provide a sustained response.
      Denosumab, as a monthly injection, led to a gradual decrement in his peak calcium
      concentrations with the values now persistently below 3 mmol/l. CONCLUSIONS:
      Denosumab, a fully human MAB that binds to the 'receptor activator of nuclear
      factor kappaB ligand (RANKL)', was shown to have a profound effect in modulating
      malignant hypercalcaemia. This medication should be considered as an effective
      option in patients with refractory hypercalcaemia secondary to parathyroid
      carcinoma.

PMID- 24743401
TI  - The diagnostic performance of urinary free cortisol is better than the
      cortisol:cortisone ratio in detecting de novo Cushing's syndrome: the use of a LC
      MS/MS method in routine clinical practice.
AB  - OBJECTIVE: The Endocrine Society Clinical Guidelines recommend measuring 24-h
      urinary free cortisol (UFF) levels using a highly accurate method as one of the
      first-line screening tests for the diagnosis of Cushing's Syndrome (CS). We
      evaluated the performance of UFF, urinary free cortisone (UFE), and the UFF:UFE
      ratio, measured using a liquid chromatography-tandem mass spectrometry (LC-MS/MS)
      method. SUBJECTS AND METHODS: The LC-MS/MS was used to analyze UFF and UFE levels
      in 43 surgically confirmed CS patients: 26 with Cushing's disease (CD, 16 de novo
      and ten recurrences), 11 with adrenal CS and six with ectopic CS; 22 CD patients
      in remission; 14 eu-cortisolemic CD patients receiving medical therapy; 60 non-CS
      patients; and 70 healthy controls. Sensitivity and specificity were determined in
      the combined groups of non-CS patients, healthy controls, and CD in remission.
      RESULTS: UFF>170 nmol/24 h showed 98.7% specificity and 100% sensitivity for de
      novo CS, while sensitivity was 80% for recurrent CD patients, who were
      characterized by lower UFF levels. The UFF:UFE and UFF+UFE showed lower
      sensitivity and specificity than UFF. Ectopic CS patients had the highest UFF and
      UFF:UFE levels, which were normal in the CD remission patients and in those
      receiving medical therapy. CONCLUSIONS: Our data suggest high diagnostic
      performance of UFF excretion measured using LC-MS/MS, in detecting de novo CS.
      UFF:UFE and UFF+UFE assessments are not useful in the first step of CS diagnosis,
      although high levels were found to be indicative of ectopic CS.

PMID- 24743400
TI  - Thyroglobulin measurement using highly sensitive assays in patients with
      differentiated thyroid cancer: a clinical position paper.
AB  - Differentiated thyroid cancer (DTC) is the most common endocrine cancer and its
      incidence has increased in recent decades. Initial treatment usually consists of
      total thyroidectomy followed by ablation of thyroid remnants by iodine-131. As
      thyroid cells are assumed to be the only source of thyroglobulin (Tg) in the
      human body, circulating Tg serves as a biochemical marker of persistent or
      recurrent disease in DTC follow-up. Currently, standard follow-up for DTC
      comprises Tg measurement and neck ultrasound combined, when indicated, with an
      additional radioiodine scan. Measurement of Tg after stimulation by endogenous or
      exogenous TSH is recommended by current clinical guidelines to detect occult
      disease with a maximum sensitivity due to the suboptimal sensitivity of older Tg
      assays. However, the development of new highly sensitive Tg assays with improved
      analytical sensitivity and precision at low concentrations now allows detection
      of very low Tg concentrations reflecting minimal amounts of thyroid tissue
      without the need for TSH stimulation. Use of these highly sensitive Tg assays has
      not yet been incorporated into clinical guidelines but they will, we believe, be
      used by physicians caring for patients with DTC. The aim of this clinical
      position paper is, therefore, to offer advice on the various aspects and
      implications of using these highly sensitive Tg assays in the clinical care of
      patients with DTC. 

PMID- 24743402
TI  - The Association of Serum Total Peptide YY (PYY) with Obesity and Body Fat
      Measures in the CODING Study.
AB  - BACKGROUND: PYY is an appetite suppressing hormone. Low circulating PYY has been
      linked to greater BMI. However data is controversial and this association has not
      been verified in large human populations. OBJECTIVE: The purpose of this study
      was to investigate if fasting serum total PYY is associated with obesity status
      and/or adiposity at the population level. DESIGN: A total of 2094 subjects (Male
      523, Female-1571) participated in this investigation. Total PYY was measured in
      fasting serum by enzyme-linked immunosorbent assay. Obesity status (NW-normal
      weight, OW-overweight and OB-obese) was determined by the Bray Criteria according
      to body fat percentage measured by dual-energy x-ray absorptiometry and the WHO
      criteria according to BMI. One-way ANOVA and multiple regression was used to
      assess the adiposity-specific association between PYY and the following; weight,
      BMI, waist-circumference, hip-circumference, waist-hip ratio, percent body fat
      (%BF), trunk fat (%TF), android fat (%AF) and gynoid fat (%GF). RESULTS: PYY was
      not significantly different among NW, OW and OB groups defined by neither %BF nor
      BMI for both men and women. However among women, fasting PYY was positively
      associated with adiposity measures. Women with the highest (Top 33%) waist
      circumference, %BF and %TF had significantly higher PYY (10.5%, 8.3% and 9.2%
      respectively) than women with the lowest (Bottom 33%). Age, smoking, medication
      use and menopause were all positively associated with PYY levels in women but not
      in men. CONCLUSION: To our knowledge this is the largest population based study,
      with the most comprehensive analysis and measures of confounding factors, to
      explore the relationship of circulating PYY with obesity. Contrary to initial
      findings in the literature we discovered that PYY was positively associated with
      body fat measures (waist-circumference, %BF and %TF) in women. Although the
      effect size of the positive association of PYY with obesity in women is small,
      and potentially negligible, it may in fact represent a protective response
      against significant weight gain.

PMID- 24743403
TI  - Comparison between kidney and continuous plasma perfusion for paraquat
      elimination.
AB  - BACKGROUND: Thousands of paraquat (PQ)-poisoned patients continue to die. Plasma
      perfusion (PP) has recently been incorporated as a method of clinical
      detoxification. The purpose of this study was to estimate the PQ clearance of PP
      and observe the effect of PP on PQ concentration in the blood of patients with
      acute PQ poisoning. METHODS: Twenty one PQ-poisoned patients admitted to our
      poisoning center within 24 hours after the ingestion were prospectively enrolled.
      Continuous plasma perfusion was performed. Urinary PQ and plasma PQ concentration
      level at inlet/outlet of the cartridge were obtained right before and 1.5 hours
      after the start of each perfusion session for the calculation of renal and plasma
      PQ excretion. RESULTS: In all 8 rounds (108 sessions) of PP on the 21 patients,
      PQ clearance rate (mL/min) by PP was always found to be higher than the renal
      value: (1st 11.14 +/- 6.13 versus 6.53 +/- 1.46; 2nd 18.36 +/- 11.32 versus 6.23
      +/- 1.51; 3rd 16.13 +/- 10.05 versus 4.01 +/- 0.93; 4th 12.86 [6.72, 17.47]
      versus 2.42 [0.65, 4.20]; 5th 14.12 [10.48, 35.20] versus 1.77 [0.63, 2.91]; 6th
      16.47 [11.82; 20.69] versus 1.70 [0.23, 3.18]; 7th 13.33 [9.71, 18.75] versus
      1.10 [0.14, 2.99]; 8th 11.27 [9.21, 16.02] versus 1.10 [0.09, 2.79], P < 0.05).
      The survivors showed a higher plasma PQ reduction rate (mg L hour) than the
      nonsurvivors (0.57 +/- 0.03 versus 0.47 +/- 0.06, P < 0.05). CONCLUSIONS: Our
      data show that PP therapies help in the clearance of PQ and may prove a promising
      therapeutic tool in patients with acute PQ intoxication.

PMID- 24743404
TI  - Cardiac sequelae of human immunodeficiency virus disease.
AB  - Presently, patients with human immunodeficiency virus infection are living longer
      and are frequently encountered in medical practice. HIV infection is a systemic
      disease, which affects a wide spectrum of organs. Cardiac involvement is
      frequent, and the consequent clinical manifestations are a common reason to seek
      medical advice. In this review, we discuss the different cardiac sequelae of HIV
      infection.

PMID- 24743405
TI  - [The role of 18F-fluorodeoxyglucose (FDG)-positron emission tomography/computed
      tomography (PET/CT) in liposarcoma of the chest wall].
AB  - 18F-fluorodeoxyglucose (FDG)-positron emission tomography/computed tomography
      (PET/CT)imaging is valuable in biopsy guidance, response assessment, grading,
      follow-up and prognostication for soft-tissue sarcoma. In liposarcoma, the
      maximum standardized uptake value (SUVmax) on PET/CT scan is correlated with the
      histological subtypes. We briefly review the role of FDG PET/CT in liposarcoma,
      and describe a case of chest wall liposarcoma treated based on the assessment
      with PET/CT. A 76-year-old man, with a 10-cm tumor at the thoracic outlet of the
      right chest wall, underwent the complete resection of the tumor according to the
      assessment with PET/CT that showed high FDG uptakeonly in the central area of the
      tumor with SUVmax of 5.89, but low uptake in the peripheral area. In accordance
      with the PET/CT findings, pathological examination revealed dedifferentiated
      liposarcoma in the central area and well-differentiated liposarcoma in the
      peripheral area. Pretherapy PET/CT should be performed for the appropriate
      treatment of liposarcoma. 

PMID- 24743406
TI  - [Current surgical treatment of primary chest wall tumor].
AB  - Primary chest wall tumor is relatively rare. According to the annual report by
      The Japanese Association for Thoracic Surgery in 2012, 447 primary chest wall
      tumors were resected in 2010. It was only 0.66% of the total number of operations
      in general thoracic surgery in Japan. From January 1992 to December 2012, 3,022
      cases in general thoracic surgery were operated in our department. Of these, 30
      patients (1%) with primary chest wall tumor were surgically treated. We
      retrospectively reviewed the medical records of them and investigated the details
      of this tumor. The patients group included 11 males and 19 females, with a mean
      age 57.6 years (range, 16 to 79 years). The majority of these patients were
      referred to us because of radiographical abnormalities on chest X-ray( 56.7%) or
      clinical symptoms( 33.3%). The operative procedure was tumor extirpation in 25
      cases and chest wall resection in 5 cases. Histologically, 23 cases (76.7%) were
      benign tumors, 7 cases (23.3%) were malignant tumors. Malignant tumors included
      aggressive and poor prognostic cases such as malignant fibrous histiocytoma or
      malignant peripheral nerve sheath tumor, on the other hand, extremely rare tumor
      with low grade malignancy such as parachordoma arising from the chest wall soft
      tissue was included. In conclusion, although, the standard therapy for malignant
      primary chest wall tumors has not been established, aggressive surgical resection
      remains the treatment of choice and to provide an accurate diagnosis.

PMID- 24743407
TI  - [Contribution of surgical margin for surgical outcome of the chest wall tumors].
AB  - We present here our institutional review of surgical treatment for the chest wall
      tumors. Chest wall resections were performed on 80 patients, and subsequent chest
      wall reconstructions were performed on 45 patients. Primary malignant tumors in
      the chest wall required more extensive rib resections combined with the
      neighboring structures such as the sternum and the vertebral bones than benign or
      metastatic/recurrent tumors did. Postoperative mortality and morbidity occurred
      in 5 patients who underwent the sternal resection and the rib resection combined
      with the vertebral bodies. Primary malignant tumors in the chest wall are
      sarcomas originating from the bones, the cartilage tissues, and the soft tissues
      of the chest wall. We general thoracic surgeons may not have expertise in
      treating sarcomas,because primary malignant chest wall tumors are rare and a
      single institution has limited experiences in surgical treatment of such tumors.
      We should be aware that a surgical margin of primary malignant chest wall tumors
      is important to achieve excellent local control and better prognosis. We
      recommend cooperation with an orthopedic oncologist who is experienced with
      treating sarcomas. Not only preoperative planning but also intraoperative
      evaluation for the surgical margin with orthopedic oncologists is necessary for
      better surgical outcome. 

PMID- 24743408
TI  - [Surgical treatment of primary chest wall tumor].
AB  - BACKGROUND: Primary chest wall tumors are uncommon and there is limited
      information in the literature regarding treatment strategies for these tumors.
      METHODS: We retrospectively reviewed 14 patients who were referred for surgical
      resection for a primary chest wall tumor. RESULTS: Except for neurogenic tumors,
      14 primary chest wall tumors were resected among 3,260 surgical cases during a 13
      year period in our institution. Complete resection was attempted for all 14
      patients;8 had benign tumors and 6 had malignant tumors. Tumor pathology was
      extremely varied as they arose from all anatomic structures of the chest wall.
      Chest wall reconstruction was performed for 7 patients;2 patients underwent an
      additional extended resection because their tumors were diagnosed as malignant
      during or after surgery;and only 1 patient with a primitive neuroectodermal tumor
      died of recurrence after surgery. CONCLUSIONS: The data and results for primary
      chest tumors are limited due to the uncommon nature of this entity and the
      extremely variable histology. In general, a preoperative diagnosis is difficult
      and a definitive diagnosis can only be made during or after surgery. Wide radical
      resection of these tumors should be attempted, particularly if malignancy is
      diagnosed.

PMID- 24743409
TI  - [Resection of chest wall tumors].
AB  - Forty-six consecutive patients with chest wall tumors undergoing resection
      between 1981 and 2012 were analyzed. There were 29 male and 17 female patients,
      with ages ranging from 15 to 77 years. Seventeen patients had primary malignant
      neoplasms, 22 had benign tumors, and 7 metastases. The primary malignant tumors
      were located in the ribs in 16 patients and sternum in one. They were resected en
      bloc in all patients. Reconstruction was with Gore-Tex( expanded
      polytetrafluoroethylene:ePTFE) in 13 patients. There was no operative death and 1
      hospital death. All patients with benign tumors survived. All patients with
      metastases died within 3 years. Seven patients with primary malignant neoplasms
      without reconstruction survived, while 5 of 10 patients undergoing reconstruction
      died between 5 and 99 months. Aggressive resection for a chest wall tumor with
      reliable reconstruction can be accomplished safely, and wide resection is a
      potentially curative treatment.

PMID- 24743410
TI  - [Chest wall reconstruction after resection of chest wall tumors].
AB  - Between 1994 and 2012, chest wall resection and reconstruction were performed 15
      patients (16 cases) with primary chest wall tumors, metastatic tumors. and chest
      wall recurrence of breast carcinoma. In all the patients, reconstruction of the
      chest wall was performed using layers of polypropylene Marlex mesh sheets. In 9
      patients, only Marlex mesh sheets were used. The post-operative course was
      uneventful, and neither paradoxical respiration nor respiratory failure was
      observed. In 2 patients, reconstructions of the sternum was performed using a
      Marlex mesh sandwich. A full thickness chest wall defect was reconstructed using
      Marlex mesh and a pedicled latissimus dorsi musculocutaneous flap. Chest wall
      recurrence of breast cancer and primary leiomyosarcoma of the chest wall were
      observed in 4 and 1 patient, respectively. In conclusion, polypropylene Marlex
      mesh sheets arranged in a layered form appear to be a stable prosthetic material
      for chest wall reconstruction. 

PMID- 24743411
TI  - [Resection and reconstruction of sternum].
AB  - We have experienced 6 cases with resection and reconstruction of sternum. They
      were 1 with osteosarcoma, 1 with synovial sarcoma, 1 with sternal metastasis of
      fallopian tube cancer, 1 with sternal metastasis of thyroid cancer, 1 with
      desmoid tumor, and 1 with dermatofibrosarcoma protuberance. Resection of both
      manubrium and sternum was performed in 3 cases and sternum resection in 3. There
      was no total resection. We used a titanium reconstruction plate and titanium mesh
      in 3 cases, a titanium reconstruction plate and polypropylene mesh in 2, titanium
      mesh in 1 for reconstruction of bony defect, and rectus abdominis myocutaneous
      flap in 3, pectralis major muscle flap in 2, latissimus doris myocutaneous flap
      in 1 for reconstruction of soft tissue defect. Postoperative courses were
      uneventful, and flail chest was not observed. Reconstruction of the bony defect
      of the anterior chest wall with the titanium reconstruction plate and titanium
      mesh or polypropylene mesh was effective by providing sufficient rigidity as well
      as protection of the thoracic organs. 

PMID- 24743412
TI  - [Reconstruction for radionecrotic chest wall ulcer using autogenous
      replacements].
AB  - When reconstructing the radionecrotic chest wall ulcer, safety of the flap is
      essential. If the flap becomes necrotic, fatal situations may arise, such as
      pyothorax, especially when prosthetic replacement is chosen. Thus, flaps with a
      rich and stable blood supply must be chosen for necrotic chest wall
      reconstruction.We present the case of a 67-year-old lady who developed
      radionecrosis following irradiation of the chest wall after radical mastectomy.
      The ensuing radionecrosis of the skin and chest wall progressed to advanced
      ischemia with secondary infection. The necrotic ribs and surrounding tissue were
      debrided and the anterior chest wall was reconstructed by pediculed omental and
      vertical rectus abdominis myocutaneous flap. The patient is currently well and
      alive without any evidence of recurrence of either infection or breast carcinoma.

PMID- 24743413
TI  - [Results of non-rigid prosthetic reconstruction with expanded polytetrafluoro
      ethylene( ePTFE) soft tissue patch following chest wall resection for malignant
      tumors].
AB  - Twenty patients underwent chest wall reconstruction using expanded
      polytetrafluoroethylene(ePTFE) soft tissue patch following resection between June
      1996 and December 2012. The patients included 15 men and 5 women, aged 18 to 80
      years. The indications for resection included 4 primary tumors, 8 metastatic
      tumors, and 8 infiltrating tumors. The lesions were located anteriorly in 10
      patients, laterally in 5 patients and posteriorly in 5 patients. Skeletal
      resection involved an average of 2 ribs in 19 patients, and a partial sternectomy
      in 1 patient. The size of chest wall defects ranged from 20 to 210 cm2( mean,
      69.8 cm2). Lung resection was performed in 7 patients included a wedge resection,
      5 lobectomy, and a bilobectomy. Chest wall defects were closed primarily with
      ePTFE soft tissue patch. There were no critical complications or postoperative
      mortalities. The mean follow-up in all patients is 72.7 months. Recurrence of
      malignancy occurred in 10 patients included a local recurrence in 1 patient, and
      metastases in 9 patients. The overall postoperative 5-year survival rate is
      61.0%. Non-rigid prosthetic reconstruction with ePTFE soft tissue patch provides
      satisfactory outcome. New prosthetic materials have to be examined whether they
      are superior to ePTFE soft tissue patch. 

PMID- 24743415
TI  - [Right ventricular outflow tract reconstruction].
AB  - With the increase of adult patients who need repeated surgery long after
      definitive repair of congenital heart defects in their childhood, right
      ventricular outflow tract reconstruction (RVOTR) is gaining more importance. From
      the viewpoint of timing and indication of surgical intervention, early primary
      repair and annulus preserving procedure have been the 2 current standards of
      RVOTR;however, long term outcome of both procedures has to be determined by
      further study. Although a wide variety for materials are used for pulmonary valve
      replacement in RVOTR, deficient longevity is one of the most common problems,
      especially when used for young patients mainly due to immunological rejection. In
      our institute, we originally developed and manufactured expanded
      polytetrafluoroethylene (ePTFE) valved patches/conduits, which showed excellent
      clinical results in a former multicenter study in Japan. This improved outcome
      may partly be attributable to the biocompatibility and low antigenicity of ePTFE
      and also to the fluid dynamical properties arising from the 2 characteristic
      structures:bulging sinus and fan-shaped valve. However, to achieve better
      patients prognosis with good quality of life,there still remains a lot of
      problems to be solved concerning RVOTR, such as indication and timing of
      definitive repair and choice of materials for pulmonary valve replacement. This
      review describes recent surgical strategies and remaining problems of RVOTR. 

PMID- 24743414
TI  - [Evaluation of long-term results in patients who underwent reconstruction of
      thoracic wall with curved metal plates].
AB  - Between 1992 and 2011, 22 patients underwent surgery of reconstruction of
      thoracic wall with curved metal plates for multiple rib fracture and resection of
      thoracic wall tumor. They were divided into 2 groups according to original
      disorders. Twelve cases of group A accepted surgical stabilization of traumatic
      multiple rib fractures with the metal plates fixed on the fractured ribs as an
      external brace. Ten patients of group B were suffered from thoracic wall tumors,
      including 1 fibrous dysplagia, 1 chondroma, 5 invasive lung cancer, 2 rib
      metastases and 1 primary chest wall cancer. After the resection of tumors, an
      average of 3.2 ribs were removed, the defects of full thickness chest wall were
      reconstructed using a combination of a polypropylene mesh and the metal plates.
      In both groups, there were no displacement of the plates and allergic reaction.
      Only 2 patients needed removal of the fixed plates due to pyothorax caused by
      pneumonia after crushing thoracic injuries. The long metal reconstruction plates
      with many perforations were very useful for reconstruction of chest wall because
      they were long enough to cover the whole length of widely resected chest defects
      and moderately soft enough to be appropriately bent or twist by hand at the time
      of operation. Moreover long-term result of the reconstructed chest wall was safe
      and satisfactory without severe complication. 

PMID- 24743416
TI  - [Mitral regurgitation and atrial septum aneurysm complicated with osteogenesis
      imperfecta; report of a case].
AB  - A 43-year-old female with a history of osteogenesis imperfecta was admitted to
      our hospital for congestive heart failure due to mitral valve regurgitation. The
      patient had suffered from bone fractures 5 times, dislocation of elbow and
      fingers 3 times since childhood, and subarachnoid hemorrhage 2 years before. She
      and her son have blue scleras. She was diagnosed with osteogenesis imperfecta
      type IA clinically. Echocardiography revealed severe mitral regurgitation and
      aneurysmal formation in the interatrial septum bulging to the right atrium.
      Mitral valve replacement and repair of the atrial septum were performed without
      any blood transfusion, but with rib fractures. Echocardiography showed no peri
      valvular regurgitation at 1 year after the valve replacement. Cardiovascular
      disease is rarely associated with osteogenesis imperfecta, but its surgical
      mortality rate is high due to coagulation abnormality and fragile tissue. To
      reduce postoperative complications, precise classification of the disease and
      careful handling of the tissues during operation will be needed. 

PMID- 24743417
TI  - [Surgical therapy for coronary artery stenosis with coronary artery aneurysm in
      the left main trunk due to Kawasaki disease; report of a case].
AB  - A 56-year-old woman was admitted for ST depression in V4 to V6 in
      electrocardiogram. Coronary angiography showed a coronary artery aneurysm with
      severe calcification on the bifurcation of the left main trunk and 99% stenosis
      in the left anterior descending artery. She did not have a history of Kawasaki
      disease in her childhood. She did not have any risk factors for ischemic heart
      disease, either. These findings suggested that the coronary artery lesions were
      related to Kawasaki disease. Percutaneous coronary intervention was impossible
      due to the location of the aneurysm which was on the bifurcation of the left main
      trunk. Single vessel coronary artery bypass grafting was performed for the
      stenosis in the left anterior descending artery. After the surgery, she was put
      on warfarin for the prevention of thrombus formation in the aneurysm. We report a
      rare case of coronary artery aneurysm due to Kawasaki disease. 

PMID- 24743418
TI  - Detecting apoptosis of leukocytes in mouse lymph nodes.
AB  - Although there are multiple methods for analyzing apoptosis in cultured cells,
      methodologies for analyzing apoptosis in vivo are sparse. In this protocol, we
      describe how to detect apoptosis of leukocytes in mouse lymph nodes (LNs) via the
      detection of apoptotic caspases. We have previously used this protocol to study
      factors that modulate dendritic cell (DC) survival in LNs; however, it can also
      be used to analyze other leukocytes that migrate to the LNs. DCs labeled with a
      fluorescent cell tracker are subcutaneously injected in the posterior footpads of
      mice. Once the labeled DCs reach the popliteal LN (PLN), the animals are
      intravenously injected with FLIVO, a permeant fluorescent reagent that
      selectively marks active caspases and consequently apoptotic cells. Explanted
      PLNs are then examined under a two-photon microscope to look for the presence of
      apoptotic cells among the DCs injected. The protocol requires 6-6.5 h for
      preparation and analysis plus an additional 34-40 h to allow apoptosis of the
      injected DCs in the PLN. 

PMID- 24743419
TI  - Multiparametric high-resolution imaging of native proteins by force-distance
      curve-based AFM.
AB  - A current challenge in the life sciences is to understand how the properties of
      individual molecular machines adjust in order to meet the functional requirements
      of the cell. Recent developments in force-distance (FD) curve-based atomic force
      microscopy (FD-based AFM) enable researchers to combine sub-nanometer imaging
      with quantitative mapping of physical, chemical and biological properties. Here
      we present a protocol to apply FD-based AFM to the multiparametric imaging of
      native proteins under physiological conditions. We describe procedures for
      experimental FD-based AFM setup, high-resolution imaging of proteins in the
      native unperturbed state with simultaneous quantitative mapping of multiple
      parameters, and data interpretation and analysis. The protocol, which can be
      completed in 1-3 d, enables researchers to image proteins and protein complexes
      in the native unperturbed state and to simultaneously map their biophysical and
      biochemical properties at sub-nanometer resolution. 

PMID- 24743420
TI  - Monitoring in vivo reversible cysteine oxidation in proteins using ICAT and mass
      spectrometry.
AB  - Reversible thiol oxidation of cysteine residues occurs in many intracellular
      catalytic and signaling processes. Here we describe an optimized protocol, which
      can be completed in ~5 d, to unambiguously identify specific cysteine residues
      that are transiently and reversibly oxidized by comparing two complex biological
      samples obtained from yeast cell cultures at the proteome level. After 'freezing'
      the in vivo thiol stage of cysteine residues by medium acidification, we first
      block reduced thiols in extracts with iodoacetamide (IAM), and then we
      sequentially reduce and label reversible oxidized thiols with the biotin-based
      heavy or light IAM derivatives, which are known as isotope-coded affinity tag
      (ICAT) reagents, so that the two samples can be compared at once after
      combination of the labeled extracts, trypsin digestion, streptavidin-affinity
      purification of peptides containing oxidized cysteines, and liquid chromatography
      tandem mass spectrometry (LC-MS/MS) analysis. For the same protein extracts,
      before cysteine-containing peptide enrichment, individual relative protein
      concentrations are obtained by stable-isotope dimethyl labeling. 

PMID- 24743421
TI  - Synthesis, labeling and bioanalytical applications of a tris(2,2'
      bipyridyl)ruthenium(II)-based electrochemiluminescence probe.
AB  - Assays using probes labeled with electrochemiluminescent moieties are extremely
      powerful analytical tools that are used in fields such as medical diagnostics,
      environmental analysis and food safety monitoring, in which sensitive, reliable
      and reproducible detection of biomolecules is a requirement. The most efficient
      electrochemiluminescence (ECL) reaction to date is based on tris(2,2'
      bipyridyl)ruthenium(II) (Ru(bpy)3(2+)) with tripropylamine (TPrA) as the co
      reactant. Here we present a detailed protocol for preparing Ru(bpy)3(2+) probes
      and their bioanalytical applications. This protocol includes (i) the synthesis of
      a biologically active Ru(bpy)3(2+)-N-hydroxysuccinimide (NHS) ester, (ii) its
      covalent labeling with both antibodies and DNA probes and (iii) the detection and
      quantification of ECL in a microfluidic system with a paramagnetic microbead
      solid support. In our magnetic bead-based ECL system, two probes are required: a
      capture probe (labeled with biotin to be captured by a streptavidin-coated
      magnetic bead) and a detector probe (labeled with Ru(bpy)3(2+)). The complex
      consisting of the analyte, the capture probe, the detector probe and the magnetic
      bead is brought into contact with the electrode by using a magnetic field. The
      Ru(bpy)3(2+) reacts with TPrA in solution to generate the ECL signal. The full
      protocol, including the synthesis and labeling of the bioactive Ru(bpy)3(2+),
      requires 5-6 d to complete. ECL immunoassays or nucleic acid tests only require
      1.5-2 h, including the sample preparation time. 

PMID- 24743422
TI  - The CpG island encompassing the promoter and first exon of human DNMT3L gene is a
      PcG/TrX response element (PRE).
AB  - DNMT3L, a member of DNA methyltransferases family, is present only in mammals. As
      it provides specificity to the action of de novo methyltransferases, DNMT3A and
      DNMT3B and interacts with histone H3, DNMT3L has been invoked as the molecule
      that can read the histone code and translate it into DNA methylation. It plays an
      important role in the initiation of genomic imprints during gametogenesis and in
      nuclear reprogramming. With important functions attributed to it, it is
      imperative that the DNMT3L expression is tightly controlled. Previously, we had
      identified a CpG island within the human DNMT3L promoter and first exon that
      showed loss of DNA methylation in cancer samples. Here we show that this
      Differentially Methylated CpG island within DNMT3L (DNMT3L DMC) acts to repress
      transcription, is a Polycomb/Trithorax Response Element (PRE) and interacts with
      both PRC1 and PRC2 Polycomb repressive complexes. In addition, it adopts inactive
      chromatin conformation and is associated with other inactive chromatin-specific
      proteins like SUV39H1 and HP1. The presence of DNMT3L DMC also influences the
      adjacent promoter to adopt repressive histone post-translational modifications.
      Due to its association with multiple layers of repressive epigenetic
      modifications, we believe that PRE within the DNMT3L DMC is responsible for the
      tight regulation of DNMT3L expression and the aberrant epigenetic modifications
      of this region leading to DNMT3L overexpression could be the reason of nuclear
      programming during carcinogenesis. 

PMID- 24743423
TI  - Language universals engage Broca's area.
AB  - It is well known that natural languages share certain aspects of their design.
      For example, across languages, syllables like blif are preferred to lbif. But
      whether language universals are myths or mentally active constraints-linguistic
      or otherwise-remains controversial. To address this question, we used fMRI to
      investigate brain response to four syllable types, arrayed on their linguistic
      well-formedness (e.g., blif?bnif?bdif?lbif, where ? indicates preference).
      Results showed that syllable structure monotonically modulated hemodynamic
      response in Broca's area, and its pattern mirrored participants' behavioral
      preferences. In contrast, ill-formed syllables did not systematically tax
      sensorimotor regions-while such syllables engaged primary auditory cortex, they
      tended to deactivate (rather than engage) articulatory motor regions. The
      convergence between the cross-linguistic preferences and English participants'
      hemodynamic and behavioral responses is remarkable given that most of these
      syllables are unattested in their language. We conclude that human brains encode
      broad restrictions on syllable structure. 

PMID- 24743424
TI  - Targets and the emergency medical system--intended and unintended consequences.
AB  - OBJECTIVE: There is interest in health service reform and efficiencies; health
      service providers collect statistics, set targets and compare institutions. In
      January 2009, in Ireland, a national waiting time target of 6 h was set from
      registration in the emergency department (ED) to admission or discharge. The aim
      of this study was to assess the consequences of the introduction of this target
      on our institution and the Acute Medical Admission Unit. METHODS: All emergency
      medical admissions were tracked over 7 years and in-hospital mortality, length of
      stay and ED 'wait' numbers and times were summarized. RESULTS: There were 43 471
      admissions in 28 862 patients. In-hospital mortality for 2006-2008 averaged 5.9%
      [95% confidence interval (CI) 5.5-6.2%] compared with 4.8% (95% CI 4.6-5.1%) for
      2009-2012 - a relative risk reduction of 18.3% (95% CI 11.5-24.5%) (P<0.001). The
      median length of stay was unaltered: 5.1 days (interquartile range 2.1-9.8)
      versus 5.0 days (interquartile range 2.0-9.5) (P=0.16). An ED 'first ward'
      allocation decreased six-fold with redistribution to the Acute Medical Admission
      Unit (two-fold increase) and the medical wards (four-fold increase). The time to
      on-call medical assessment decreased (time to team pre/post 4.5 vs. 4.2 h,
      P<0.001). However, calculations directly on the real-time log of arrival and
      first in-patient time showed a worsening of the position (time to ward pre/post
      7.1 vs. 8.4 h, P<0.001). CONCLUSION: Target setting may result in unintended
      consequences in other areas in addition to its stated goal. These unintentional
      consequences of targets should be borne in mind by those planning and instituting
      healthcare reform.

PMID- 24743425
TI  - External validation of the MISSED score to predict mortality in patients with
      severe sepsis and septic shock in the emergency department.
AB  - OBJECTIVE: The Mortality in Severe Sepsis in the Emergency Department (MISSED)
      score was derived to predict in-hospital mortality in septic patients in the
      emergency department (ED). The present study aimed to validate the MISSED score
      in patients receiving early goal-directed therapy (EGDT). METHODS: Data were
      analyzed from 280 patients who received EGDT in a tertiary center ED in Korea.
      Age 65 years and above, albumin level 27 g/l or less, and international
      normalized ratio of at least 1.2 were variables included in the MISSED score.
      RESULTS: With a cutoff point of 5.5, the odds ratio for death was 2.17 (95%
      confidence interval 1.18-4.02). Mortality rates with MISSED scores of 0,< 5.5,
      and >= 5.5 were 4.5, 13.4, and 25.2%, respectively. Although the score was less
      discriminatory in patients who had EGDT commenced in the ED, a MISSED score
      higher than 5.5 remained significant. CONCLUSION: Further studies are required to
      validate the MISSED score in more diverse patients.

PMID- 24743426
TI  - Design and validation of novel scattering foils for modulated electron radiation
      therapy.
AB  - Modulated Electron Radiation Therapy (MERT) continues to be an area of interest
      to various groups, however, the scattering foils used in beam flattening have not
      been optimized for this modality. In this work, the feasibility of novel
      scattering foils specifically designed for MERT is investigated using Monte Carlo
      methods. Different designs based on foil material, shape and thickness were
      analyzed. It was shown that low atomic number materials such as aluminum were
      optimal, while shaped foils such as those employed in current dual foil designs
      were not necessary. Aluminum foil thickness between 0.36 mm and 1.50 mm were
      capable of sufficiently broadening beams with energies between 12 MeV and 20 MeV
      respectively, with beams of lower energies receiving sufficient scatter from the
      treatment head components and air scatter. Finally, custom foils were
      manufactured based upon previously simulated designs and were placed into the
      beamline of a 2100 EX accelerator, and showed excellent agreement between the
      simulated and measured PDDs and profiles. Custom foils achieved higher dose rates
      on the central axis compared to the clinical foils by factors of 5.4, 4.9 and 4.5
      for 12 MeV, 16 MeV and 20 MeV, respectively. 

PMID- 24743427
TI  - The relationship between TTF-1 expression and EGFR mutations in lung
      adenocarcinomas.
AB  - OBJECTIVE: To explore the relationship between TTF-1 and EGFR mutations in lung
      adenocarcinoma tissues to guide clinical treatment timely and effectively.
      MATERIALS AND METHODS: we collected 664 tissue samples from patients with
      histologically confirmed lung adenocarcinoma from May 2010 to April 2013. All
      tumor tissues were collected prior to administering therapy. TTF-1 was detected
      by immunohistochemistry and EGFR mutations by DNA direct sequencing. Finally, the
      correlation between TTF-1 expression and the presence of EGFR mutations was
      analyzed using chi2 test or Fisher's exact test with SPSS software version 18.0.
      RESULTS: Of the 664 lung adenocarcinoma tissue samples, 18 were partially
      positive for TTF-1 (+-), and 636 were positive for TTF-1 (+) resulting in a total
      positive rate of 98.49% (+,+-)(including partial positive). In only 10 cases was
      the TTF-1 negative (-); the negative rate was 1.51%. There were 402 cases without
      an EGFR mutation and 262 cases with EGFR mutations; the rate of mutations was
      39.46%. The location of the EGFR mutation was exon 19 for 121 cases resulting in
      a mutation rate in exon 19 of 18.22%. The location of the EGFR mutation was exon
      21 for 141 cases resulting in a mutation rate in exon 21 of 21.23%. Exon 18 and
      20 detected by DNA direct sequencing no mutations.A Fisher's exact test was used
      to determine the correlation between EGFR mutations and TTF-1 expression.for the
      whole, TTF-1 positive expression(including partial positive) has correlation with
      EGFR mutations (p<0.001),especially for Exon 21 expression,the correlation is
      significant (p = 0.008). CONCLUSION: In lung adenocarcinomas, positive and
      partial positive TTF-1 expression has a significant positive correlation with
      EGFR mutations(exon 19 and 21). In clinical practice, TTF-1 expression combine
      with EGFR mutations, especially exon 21 mutation can guide clinical treatment
      timely for lung adenocarcinomas.

PMID- 24743428
TI  - Ectopic fat, insulin resistance, and nonalcoholic fatty liver disease:
      implications for cardiovascular disease.
AB  - Ectopic fat accumulation in the liver causes nonalcoholic fatty liver disease
      (NAFLD), which is the most common cause of chronic liver disease in Western
      countries. Ectopic liver lipid, particularly diacylglycerol, exacerbates hepatic
      insulin resistance, promotes systemic inflammation, and increases risk of
      developing both type 2 diabetes mellitus and cardiovascular disease. Increasing
      evidence suggests that NAFLD is an emerging risk factor for cardiovascular
      disease, and although there are currently no licensed treatments for NAFLD per
      se, current evidence suggests that statin treatment is safe in NAFLD. Presently,
      there is insufficient evidence to indicate that statins or other cardioprotective
      agents, such as angiotensin receptor blockers, are effective in treating NAFLD.
      In this brief narrative review, we discuss the diagnosis of NAFLD and the role of
      ectopic liver fat to cause insulin resistance and to increase risk of both type 2
      diabetes mellitus and cardiovascular disease. For this review, PubMed was
      searched for articles using the key words non-alcoholic fatty liver disease or
      fatty liver combined with diabetes risk, cardiovascular risk, and cardiovascular
      mortality between 1990 and 2014. Articles published in languages other than
      English were excluded.

PMID- 24743429
TI  - Complement 5a receptor mediates angiotensin II-induced cardiac inflammation and
      remodeling.
AB  - OBJECTIVE: Inflammation contributes to hypertension-induced cardiac damage and
      fibrotic remodeling. Complement activation produces anaphylatoxins, which are
      major inflammatory effectors. Here, we investigated the role of complement
      anaphylatoxins in angiotensin II (Ang II)-induced cardiac remodeling. APPROACH
      AND RESULTS: We measured human plasma levels of complement anaphylatoxins in
      hypertensive individuals and controls and studied the role of complement
      activation in a mouse model of Ang II-induced hypertension and cardiac injury. We
      found that complement 5a (C5a) concentration was more elevated in hypertensive
      individuals than in controls. Infusion of Ang II in mice for 7 days led to
      increased anaphylatoxin concentration in plasma and perivascular C3b deposition
      in the heart. C5a receptor (C5aR)-deficient but not C3a receptor-deficient mice
      exhibited markedly reduced cardiac remodeling and inflammation after Ang II
      infusion. Pharmacological inhibition of C5a production by an anti-C5 monoclonal
      antibody produced similar effects to C5aR deficiency. Bone marrow chimera
      experiments revealed that C5aR expression on bone marrow-derived cells was
      critical in mediating Ang II-induced cardiac injury and remodeling. The C5aR
      pathway regulated the expression of adhesion molecules on peripheral monocytes,
      as well as infiltration and cytokine production of macrophage in the heart.
      CONCLUSIONS: Complement is activated in hypertensive hearts, and the C5aR
      signaling pathway on blood monocytes/macrophages plays a pathological role in Ang
      II-induced cardiac inflammation and remodeling. Therapeutic inhibition of
      complement may protect patients from hypertension-related heart injury.

PMID- 24743430
TI  - Specific role of impaired glucose metabolism and diabetes mellitus in endothelial
      progenitor cell characteristics and function.
AB  - The disease burden of diabetes mellitus (DM) and its associated cardiovascular
      complications represent a growing and major global health problem. Recent studies
      suggest that circulating exogenous endothelial progenitor cells (EPCs) play an
      important role in endothelial repair and neovascularization at sites of injury or
      ischemia. Both experimental and clinical studies have demonstrated that
      hyperglycemia related to DM can induce alterations to EPCs. The reduction and
      dysfunction of EPCs related to DM correlate with the occurrence and severity of
      microvascular and macrovascular complications, suggesting a close mechanistic
      link between EPC dysfunction and impaired vascular function/repair in DM. These
      alterations to EPCs, likely mediated by multiple pathophysiological mechanisms,
      including inflammation, oxidative stress, and alterations in Akt and the nitric
      oxide pathway, affect EPCs at multiple stages: differentiation and mobilization
      in the bone marrow, trafficking and survival in the circulation, and homing and
      neovascularization. Several different therapeutic approaches have consequently
      been proposed to reverse the reduction and dysfunction of EPCs in DM and may
      represent a novel therapeutic approach to prevent and treat DM-related
      cardiovascular complications.

PMID- 24743431
TI  - Effects of fenofibric acid on carotid intima-media thickness in patients with
      mixed dyslipidemia on atorvastatin therapy: randomized, placebo-controlled study
      (FIRST).
AB  - OBJECTIVE: To assess whether adding a fibrate to statin therapy reduces residual
      cardiovascular risk associated with elevated triglycerides and low high-density
      lipoprotein cholesterol, The Evaluation of Choline Fenofibrate (ABT-335) on
      Carotid Intima-Media Thickness (cIMT) in Subjects with Type IIb Dyslipidemia with
      Residual Risk in Addition to Atorvastatin Therapy (FIRST) trial evaluated the
      effects of fenofibric acid (FA) treatment on cIMT in patients with mixed
      dyslipidemia on atorvastatin. APPROACH AND RESULTS: This multicenter, double
      blind, placebo-controlled study was performed in patients with mixed dyslipidemia
      (fasting triglycerides, >=150 mg/dL; high-density lipoprotein cholesterol, <=45
      [men] or 55 mg/dL [women]; low-density lipoprotein cholesterol, <=100 mg/dL once
      and averaging <=105 mg/dL) and a history of coronary heart disease or risk
      equivalent. Patients on background atorvastatin (continued on starting dose or
      titrated to 40 mg, if needed) were randomized to FA 135 mg or placebo. The
      primary end point was rate of change from baseline through week 104 of the mean
      posterior-wall cIMT, measured by ultrasound. In patients with controlled low
      density lipoprotein cholesterol while on atorvastatin background therapy, rate of
      change in posterior-wall cIMT was similar with FA plus atorvastatin (-0.006 mm/y)
      versus atorvastatin monotherapy (0.000 mm/y; P=0.22). FA plus atorvastatin was
      favored (P<0.05) in 5 of 24 prespecified subgroups: age >=60 years, history of
      coronary artery disease, cIMT >0.795 mm, triglycerides 170 to 235 mg/dL, and
      statin use at entry. Adverse events were consistent with the known safety
      profiles of both drugs; however, FA plus atorvastatin was associated with a
      greater incidence of renal-related adverse events compared with atorvastatin
      monotherapy (6.5% versus 0.9%). CONCLUSIONS: Compared with atorvastatin
      monotherapy, FA plus atorvastatin did not further decrease cIMT progression in
      high-risk patients with mixed dyslipidemia.

PMID- 24743432
TI  - Anti-inflammatory effects of high-density lipoprotein through activating
      transcription factor 3: benefit beyond cholesterol transport-dependent processes.

PMID- 24743433
TI  - Preexisting cerebral microbleeds on susceptibility-weighted magnetic resonance
      imaging and post-thrombolysis bleeding risk in 392 patients.
AB  - BACKGROUND AND PURPOSE: The question whether cerebral microbleeds (CMBs) visible
      on MRI in acute stroke increase the risk for intracerebral hemorrhages (ICHs) or
      worse outcome after thrombolysis is unresolved. The aim of this study was to
      analyze the impact of CMB detected with pretreatment susceptibility-weighted MRI
      on ICH occurrence and outcome. METHODS: From 2010 to 2013 we treated 724 patients
      with intravenous thrombolysis, endovascular therapy, or intravenous thrombolysis
      followed by endovascular therapy. A total of 392 of the 724 patients were
      examined with susceptibility-weighted MRI before treatment. CMBs were rated
      retrospectively. Multivariable regression analysis was used to determine the
      impact of CMB on ICH and outcome. RESULTS: Of 392 patients, 174 were treated with
      intravenous thrombolysis, 150 with endovascular therapy, and 68 with intravenous
      thrombolysis followed by endovascular therapy. CMBs were detected in 79 (20.2%)
      patients. Symptomatic ICH occurred in 21 (5.4%) and asymptomatic in 75 (19.1%)
      patients, thereof 61 (15.6%) bleedings within and 35 (8.9%) outside the infarct.
      Neither the existence of CMB, their burden, predominant location nor their
      presumed pathogenesis influenced the risk for symptomatic or asymptomatic ICH. A
      higher CMB burden marginally increased the risk for ICH outside the infarct
      (P=0.048; odds ratio, 1.004; 95% confidence interval, 1.000-1.008). CONCLUSIONS:
      CMB detected on pretreatment susceptibility-weighted MRI did not increase the
      risk for ICH or worsen outcome, even when CMB burden, predominant location, or
      presumed pathogenesis was considered. There was only a small increased risk for
      ICH outside the infarct with increasing CMB burden that does not advise against
      thrombolysis in such patients.

PMID- 24743434
TI  - Are we ready to translate T-cell transmigration in stroke?

PMID- 24743436
TI  - Response to letter regarding article, "anticoagulants for cerebral venous
      thrombosis: harmful to patients?".

PMID- 24743435
TI  - Blocking of alpha4 integrin does not protect from acute ischemic stroke in mice.
AB  - BACKGROUND AND PURPOSE: T lymphocytes have recently been identified as key
      mediators of tissue damage in ischemic stroke. The interaction between very late
      antigen-4 (VLA-4) and vascular adhesion molecule-1 is crucial for the
      transvascular egress of T lymphocytes, and inhibition of this interaction by
      specific antibodies is a powerful strategy to combat autoimmune
      neuroinflammation. However, whether pharmacological blocking of T-lymphocyte
      trafficking is also protective during brain ischemia is still unclear. We
      investigated the efficacy of a monoclonal antibody directed against VLA-4 in
      mouse models of ischemic stroke. METHODS: Transient and permanent middle cerebral
      artery occlusion was induced in male C57Bl/6 mice. Animals treated with a
      monoclonal anti-CD49d antibody (300 MUg) 24 hours before or 3 hours after the
      onset of cerebral ischemia and stroke outcome, including infarct size, functional
      status, and mortality, were assessed between day 1 and day 7. The numbers of
      immune cells invading the ischemic brain were determined by immunocytochemistry
      and flow cytometry. RESULTS: Blocking of VLA-4 significantly reduced the invasion
      of T lymphocytes and neutrophils on day 5 after middle cerebral artery occlusion
      and inhibited the upregulation of vascular adhesion molecule-1. However, the anti
      CD49d antibody failed to influence stroke outcome positively irrespective of the
      model or the time point investigated. CONCLUSIONS: Pharmacological inhibition of
      the VLA-4/vascular adhesion molecule-1 axis in experimental stroke was
      ineffective in our hands. Our results cast doubt on the effectiveness of anti
      CD49d as a stroke treatment. Further translational studies should be performed
      before testing anti-VLA-4 antibodies in patients with stroke.

PMID- 24743437
TI  - The art of estimating outcomes and treating patients with stroke in the 21st
      century.

PMID- 24743438
TI  - Isolated cortical vein thrombosis: systematic review of case reports and case
      series.
AB  - BACKGROUND AND PURPOSE: Isolated cortical vein thrombosis is a distinct subtype
      of cerebral venous and sinus thrombosis. Because of the rarity of isolated
      cortical vein thrombosis, limited knowledge on its clinical and radiological
      manifestations is available. METHODS: We performed a systematic review of
      published data. Isolated cortical vein thrombosis had to have been diagnosed by
      MRI, conventional angiography, computed tomography venography, autopsy, or
      surgery. Cases with concurrent thrombosis of a cerebral sinus were excluded.
      RESULTS: Of 175 potentially relevant studies, 47 were included in the analysis,
      with a total of 116 patients. All studies were case reports and case series. Mean
      age was 41 years and 68% were women. The most common symptoms were headache
      (71%), seizures (58%), and focal neurological deficits (62%). Papilledema was not
      reported in any patient, and increased cerebrospinal fluid pressure was reported
      only in 2. Infection (19%), pregnancy or puerperium (35% of women), and oral
      contraceptive use (21% of women) were the most common risk factors. Most cases
      (73%) were diagnosed with MRI, but conventional angiography was also performed in
      47%. A total of 81% had a parenchymal brain lesion and 80% were treated with
      anticoagulation. In-hospital mortality was 6%. CONCLUSIONS: Signs of increased
      intracranial pressure seem to be less common in isolated cortical vein thrombosis
      compared with cerebral venous and sinus thrombosis. MRI and in some cases
      conventional angiography are the most frequently used diagnostic modalities and
      anticoagulation is the most widely used therapy.

PMID- 24743439
TI  - Letter by Misra et al regarding article, "anticoagulants for cerebral venous
      thrombosis: harmful to patients?".

PMID- 24743440
TI  - Effect of dietary modification on incident carotid artery disease in
      postmenopausal women: results from the women's health initiative dietary
      modification trial.
AB  - BACKGROUND AND PURPOSE: Because the diagnosis and treatment of carotid artery
      disease may reduce the rate of stroke, the aim of this study was to determine
      whether a diet intervention was associated with incident carotid artery disease.
      METHODS: Participants were 48 835 postmenopausal women aged 50 to 79 years who
      were randomly assigned to either the intervention or comparison group in the
      Women's Health Initiative Diet Modification Trial. Incident carotid artery
      disease was defined as an overnight hospitalization with either symptoms or a
      surgical intervention to improve flow. RESULTS: After a mean follow-up of 8.3
      years from 1994 to 2005, there were 297 (0.61%) incident carotid artery events.
      In contrast to the comparison group, the risk of incident carotid disease did not
      differ from those assigned to the intervention group (hazard ratio, 1.08; 95%
      confidence interval, 0.9-1.4). In secondary analysis, there was no significant
      effect of the intervention on the risk for incident carotid disease during the 5
      years of postintervention follow-up from 2005 to 2010 (hazard ratio, 1.24; 95%
      confidence interval, 0.9-1.7) and no significant effect during cumulative follow
      up from 1994 to 2010 (hazard ratio, 1.13; 95% confidence interval, 0.9-1.4).
      CONCLUSIONS: Among postmenopausal women, a dietary intervention aimed at reducing
      total fat intake and encouraging increased intake of fruit, vegetables, and
      grains did not significantly change the risk for incident carotid artery disease.
      CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique
      identifier: NCT00000611.

PMID- 24743441
TI  - Opposing effects of glucose on stroke and reperfusion injury: acidosis, oxidative
      stress, and energy metabolism.

PMID- 24743442
TI  - Sleep duration and risk of stroke mortality among Chinese adults: Singapore
      Chinese health study.
AB  - BACKGROUND AND PURPOSE: Prospective relation between sleep duration and stroke
      risk is less studied, particularly in Asians. We examined the association between
      sleep duration and stroke mortality among Chinese adults. METHODS: The Singapore
      Chinese Health Study is a population-based cohort of 63 257 Chinese adults aged
      45 to 74 years enrolled during 1993 through 1998. Sleep duration at baseline was
      assessed via in-person interview, and death information during follow-up was
      ascertained via record linkage with the death registry up to December 31, 2011.
      Cox proportional hazard models were used to calculate hazard ratios with
      adjustment for other comorbidities and lifestyle risk factors of stroke
      mortality. RESULTS: During 926 752 person-years of follow-up, we documented 1381
      stroke deaths (322 from hemorrhagic and 1059 from ischemic or nonspecified
      strokes). Compared with individuals with 7 hours per day of sleep, the
      multivariate-adjusted hazard ratio (95% confidence interval) of total stroke
      mortality was 1.25 (1.05-1.50) for <=5 hours per day (short duration), 1.01 (0.87
      1.18) for 6 hours per day, 1.09 (0.95-1.26) for 8 hours per day, and 1.54 (1.28
      1.85) for >=9 hours per day (long duration). The increased risk of stroke death
      with short (1.54; 1.16-2.03) and long durations of sleep (1.95; 1.48-2.57) was
      seen among subjects with a history of hypertension, but not in those without
      hypertension. These findings were limited to risk of death from ischemic or
      nonspecified stroke, but not observed for hemorrhagic stroke. CONCLUSIONS: Both
      short and long sleep durations are associated with increased risk of stroke
      mortality in a Chinese population, particularly among those with a history of
      hypertension.

PMID- 24743443
TI  - Totaled health risks in vascular events score predicts clinical outcomes in
      patients with cardioembolic and other subtypes of ischemic stroke.
AB  - BACKGROUND AND PURPOSE: Whether totaled health risks in vascular events (THRIVE)
      score can be used to predict clinical outcomes and risk of hemorrhagic
      transformation in patients with special subtypes of ischemic stroke remains an
      open question. METHODS: We analyzed the possible relationships between THRIVE
      score and clinical outcomes in patients with cardioembolic stroke or
      noncardioembolic stroke who did not receive thrombolytic therapy. Clinical
      outcomes and hemorrhagic transformation within 3 months of admission were
      compared among 3 patient subgroups with initial THRIVE scores of 0 to 2, 3 to 5,
      or 6 to 9. RESULTS: A total of 505 patients with cardioembolic stroke and 3374
      patients with noncardioembolic stroke were included in our analysis. As THRIVE
      score increased, the rate of patients showing good clinical outcome decreased,
      whereas the rate of mortality and hemorrhagic transformation increased after
      ischemic stroke. Increasing THRIVE score was independently associated with
      decreasing likelihood of good outcome, defined as a modified Rankin Scale score
      of 0 to 2 (cardioembolic stroke: odds ratio, 0.59; 95% confidence interval, 0.51
      0.67; noncardioembolic stroke: odds ratio, 0.53; 95% confidence interval, 0.49
      0.57), and with increasing likelihood of death (cardioembolic: odds ratio, 1.48;
      95% confidence interval, 1.28-1.70; noncardioembolic: odds ratio, 1.95; 95%
      confidence interval, 1.76-2.16). THRIVE score showed good receiver operating
      characteristics for predicting good outcome and mortality in patients with
      cardioembolic stroke and noncardioembolic stroke. CONCLUSIONS: The THRIVE score
      is a simple tool that helps clinicians estimate good outcome and death after
      ischemic stroke.

PMID- 24743444
TI  - Intracranial hemorrhage among patients with atrial fibrillation anticoagulated
      with warfarin or rivaroxaban: the rivaroxaban once daily, oral, direct factor Xa
      inhibition compared with vitamin K antagonism for prevention of stroke and
      embolism trial in atrial fibrillation.
AB  - BACKGROUND AND PURPOSE: Intracranial hemorrhage (ICH) is a life-threatening
      complication of anticoagulation. METHODS: We investigated the rate, outcomes, and
      predictors of ICH in 14 264 patients with atrial fibrillation from Rivaroxaban
      Once Daily, Oral, Direct Factor Xa Inhibition Compared With Vitamin K Antagonism
      for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF).
      Cox proportional hazards modeling was used. RESULTS: During 1.94 years (median)
      of follow-up, 172 patients (1.2%) experienced 175 ICH events at a rate of 0.67%
      per year. The significant, independent predictors of ICH were race (Asian: hazard
      ratio, 2.02; 95% CI, 1.39-2.94; black: hazard ratio, 3.25; 95% CI, 1.43-7.41),
      age (1.35; 1.13-1.63 per 10-year increase), reduced serum albumin (1.39; 1.12
      1.73 per 0.5 g/dL decrease), reduced platelet count below 210*10(9)/L (1.08; 1.02
      1.13 per 10*10(9)/L decrease), previous stroke or transient ischemic attack
      (1.42; 1.02-1.96), and increased diastolic blood pressure (1.17; 1.01-1.36 per 10
      mm Hg increase). Predictors of a reduced risk of ICH were randomization to
      rivaroxaban (0.60; 0.44-0.82) and history of congestive heart failure (0.65; 0.47
      0.89). The ability of the model to discriminate individuals with and without ICH
      was good (C-index, 0.69; 95% CI, 0.64-0.73). CONCLUSIONS: Among patients with
      atrial fibrillation treated with anticoagulation, the risk of ICH was higher
      among Asians, blacks, the elderly, and in those with previous stroke or transient
      ischemic attack, increased diastolic blood pressure, and reduced platelet count
      or serum albumin at baseline. The risk of ICH was significantly lower in patients
      with heart failure and in those who were randomized to rivaroxaban instead of
      warfarin. The external validity of these findings requires testing in other
      atrial fibrillation populations.

PMID- 24743445
TI  - Evaluation of dexmedetomidine and postoperative pain management in patients with
      adolescent idiopathic scoliosis: conclusions based on a retrospective study at a
      tertiary pediatric hospital.
AB  - OBJECTIVES: This study evaluated the effectiveness of dexmedetomidine in
      decreasing opioid use in children with adolescent idiopathic scoliosis following
      posterior spinal fusion surgery at a pediatric tertiary care hospital over the
      past 10 years. DESIGN: This was a retrospective chart review. Patients were
      separated into two groups: those that received opioid via patient-controlled
      analgesia pain therapy alone and those that received opioid via patient
      controlled analgesia pain therapy with dexmedetomidine. SETTING: A tertiary
      pediatric free-standing hospital. The study focused on care administered in the
      perioperative period, including the operating room, ICU, and general hospital
      floor. PATIENTS: One hundred sixty-three children with adolescent idiopathic
      scoliosis. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Measurements
      included patient demographics, American Society of Anesthesiologists Physical
      Status Classification System, levels of spinal fusion, length of hospital stay,
      complications, numeric pain scores, opioid requirement, elastomeric pain pump
      use, length of time until ambulation, adverse effects, and naloxone use. Data
      were collected through the first 72 hours of the perioperative period. One
      hundred six patients received opioids via patient-controlled analgesia therapy
      with dexmedetomidine and 57 received opioids via patient-controlled analgesia
      alone. Within the groups, there were 46 patients who received local anesthetic
      infusions via elastomeric pumps in the patient-controlled analgesia with
      dexmedetomidine group and 16 patients had pumps in the patient-controlled
      analgesia-alone group. There was no overall difference in postoperative use of
      morphine (or equivalents) between the two groups. However, the use of elastomeric
      pain pumps demonstrated a statistically significant decrease in mean overall
      opioid consumption (42.6 mg vs 63.1 mg, p < 0.001). CONCLUSIONS: There was no
      difference in opioid use related to dexmedetomidine on any postoperative day. The
      only variable showing a significant opioid sparing effect was the use of local
      anesthetic infusions via elastomeric pumps. Using continuous local anesthetic
      infusions instead of dexmedetomidine could eliminate the need for ICU admission,
      require shorter hospital stays, and reduce costs while still providing safe and
      effective pain control.

PMID- 24743446
TI  - Vaccines against cancer: Despite setbacks, attempts to harness the patient's
      immune system to fight tumor cells show promise in clinical trials.

PMID- 24743448
TI  - Discrimination between weaned and unweaned Atlantic cod (Gadus morhua) in capture
      based aquaculture (CBA) by X-ray imaging and radio-frequency metal detector.
AB  - The aim of this study was to investigate the feasibility of two detection methods
      for use in discrimination and sorting of adult Atlantic cod (about 2 kg) in the
      small scale capture-based aquaculture (CBA). Presently, there is no established
      method for discrimination of weaned and unweaned cod in CBA. Generally, 60-70% of
      the wild-caught cod in the CBA are weaned into commercial dry feed. To increase
      profitability for the fish farmers, unweaned cod must be separated from the
      stock, meaning the fish must be sorted into two groups - unweaned and weaned from
      moist feed. The challenges with handling of large numbers of fish in cages,
      defined the limits of the applied technology. As a result, a working model was
      established, focusing on implementing different marking materials added to the
      fish feed, and different technology for detecting the feed presence in the fish
      gut. X-ray imaging in two modes (planar and dual energy band) and sensitive radio
      frequency metal detection were the detection methods that were chosen for the
      investigations. Both methods were tested in laboratory conditions using dead fish
      with marked feed inserted into the gut cavity. In particular, the sensitive radio
      frequency metal detection method with carbonyl powder showed very promising
      results in detection of marked feed. Results show also that Dual energy band X
      ray imaging may have potential for prediction of fat content in the feed. Based
      on the investigations it can be concluded that both X-ray imaging and sensitive
      radio-frequency metal detector technology have the potential for detecting cod
      having consumed marked feed. These are all technologies that may be adapted to
      large scale handling of fish from fish cages. Thus, it may be possible to
      discriminate between unweaned and weaned cod in a large scale grading situation.
      Based on the results of this study, a suggestion for evaluation of concept for in
      situ sorting system is presented. 

PMID- 24743447
TI  - The trajectory of dispersal research in conservation biology. Systematic review.
AB  - Dispersal knowledge is essential for conservation management, and demand is
      growing. But are we accumulating dispersal knowledge at a pace that can meet the
      demand? To answer this question we tested for changes in dispersal data
      collection and use over time. Our systematic review of 655 conservation-related
      publications compared five topics: climate change, habitat restoration,
      population viability analysis, land planning (systematic conservation planning)
      and invasive species. We analysed temporal changes in the: (i) questions asked by
      dispersal-related research; (ii) methods used to study dispersal; (iii) the
      quality of dispersal data; (iv) extent that dispersal knowledge is lacking, and;
      (v) likely consequences of limited dispersal knowledge. Research questions have
      changed little over time; the same problems examined in the 1990s are still being
      addressed. The most common methods used to study dispersal were occupancy data,
      expert opinion and modelling, which often provided indirect, low quality
      information about dispersal. Although use of genetics for estimating dispersal
      has increased, new ecological and genetic methods for measuring dispersal are not
      yet widely adopted. Almost half of the papers identified knowledge gaps related
      to dispersal. Limited dispersal knowledge often made it impossible to discover
      ecological processes or compromised conservation outcomes. The quality of
      dispersal data used in climate change research has increased since the 1990s. In
      comparison, restoration ecology inadequately addresses large-scale process,
      whilst the gap between knowledge accumulation and growth in applications may be
      increasing in land planning. To overcome apparent stagnation in collection and
      use of dispersal knowledge, researchers need to: (i) improve the quality of
      available data using new approaches; (ii) understand the complementarities of
      different methods and; (iii) define the value of different kinds of dispersal
      information for supporting management decisions. Ambitious, multi-disciplinary
      research programs studying many species are critical for advancing dispersal
      research. 

PMID- 24743449
TI  - Sphingosine 1-phosphate (S1P) induced interleukin-8 (IL-8) release is mediated by
      S1P receptor 2 and nuclear factor kappaB in BEAS-2B cells.
AB  - The airway epithelium may release pro-inflammatory cytokines and chemokines in
      the asthmatic airway. Sphingosine 1-phosphate (S1P) is a bioactive lipid,
      increased in the airways of asthmatics, that may trigger the release of the
      potent neutrophil chemoattractant Interleukin-8 (IL-8) by epithelial cells. S1P
      is a ligand for 5 G protein-coupled receptors, S1PR1-5. We wished to explore the
      mechanisms of S1P induced IL-8 secretion with regard to the receptor(s) and
      downstream signaling events involved. Our results indicate that S1P induced IL-8
      release is mediated by S1PR2 and the transcription factor NF-kappaB. Since the
      Epidermal Growth Factor Receptor (EGFR) and reactive oxygen species (ROS) have
      been implicated in IL-8 release in response to activation of other G protein
      coupled receptors, we examined their importance in S1P induced IL-8 release and
      established that they are not involved. This study reveals S1PR2 and NF-kappaB as
      potential therapeutic targets in neutrophilic airway diseases such as severe
      asthma.

PMID- 24743450
TI  - Epigenetic regulation by heritable RNA.
AB  - Genomic concepts are based on the assumption that phenotypes arise from the
      expression of genetic variants. However, the presence of non-Mendelian
      inheritance patterns provides a direct challenge to this view and suggests an
      important role for alternative mechanisms of gene regulation and inheritance.
      Over the past few years, a highly complex and diverse network of noncoding RNAs
      has been discovered. Research in animal models has shown that RNAs can be
      inherited and that RNA methyltransferases can be important for the transmission
      and expression of modified phenotypes in the next generation. We discuss possible
      mechanisms of RNA-mediated inheritance and the role of these mechanisms for human
      health and disease. 

PMID- 24743451
TI  - Transfemoral prosthesis suspension systems: a systematic review of the
      literature.
AB  - The purpose of this study was to find the scientific evidence pertaining to
      various transfemoral suspension systems to provide selection criteria for
      clinicians. To this end, databases of PubMed, Web of Science, and ScienceDirect
      were explored. The following key words, as well as their combinations and
      synonyms, were used for the search: transfemoral prosthesis, prosthetic
      suspension, lower limb prosthesis, above-knee prosthesis, prosthetic liner,
      transfemoral, and prosthetic socket. The study design, research instrument,
      sampling method, outcome measures, and protocols of articles were reviewed. On
      the basis of the selection criteria, 16 articles (11 prospective studies and 5
      surveys) were reviewed. The main causes of reluctance to prosthesis, aside from
      energy expenditure, were socket-related problems such as discomfort,
      perspiration, and skin problems. Osseointegration was a suspension option, yet it
      is rarely applied because of several drawbacks, such as extended rehabilitation
      process, risk for fracture, and infection along with excessive cost. In
      conclusion, no clinical evidence was found as a "standard" system of suspension
      and socket design for all transfemoral amputees. However, among various
      suspension systems for transfemoral amputees, the soft insert or double socket
      was favored by most users in terms of function and comfort. 

PMID- 24743452
TI  - Sonography of the median nerve in carpal tunnel syndrome with diabetic
      neuropathy.
AB  - OBJECTIVE: The aim of this study was to determine the criteria for
      ultrasonographic measurement of the cross-sectional area (CSA) of the median
      nerve and differential diagnosis of patients with carpal tunnel syndrome (CTS)
      with or without diabetic polyneuropathy (DPN). DESIGN: One hundred eighty-seven
      patients were divided into five groups: healthy controls, CTS, diabetes with CTS
      but without DPN, DPN only, and both DPN and CTS. The CSAs of the median nerve
      were measured at four levels, and cutoff values to diagnose CTS with DPN were
      obtained. RESULTS: All the CSAs were larger in the DPN group compared with those
      in the control group. The CSAs of the median nerve at the wrist revealed no
      significant differences among the groups with CTS; however, these groups
      demonstrated larger CSAs at the wrist and a higher wrist/forearm ratio compared
      with the DPN only group. The cutoff value for the CSA at the wrist that yielded
      the highest sensitivity and specificity was 11.6 mm. CONCLUSIONS: The CSA of the
      median nerve at the wrist and the wrist/forearm ratio could be useful for
      diagnosing the comorbidity of CTS with DPN.

PMID- 24743453
TI  - Impact of exercise-induced fatigue on the strength, postural control, and gait of
      children with a neuromuscular disease.
AB  - OBJECTIVE: Children with a neuromuscular disease are prone to early muscular
      fatigue. The objective of the present study was to evaluate the effects of
      fatigue induced by a walking exercise on the strength, postural control, and gait
      of children with a neuromuscular disease. DESIGN: Maximal isometric knee strength
      (extension and flexion), quiet standing postural control, and gait were evaluated
      in 12 children (8.8 [1.4] yrs) with a neuromuscular disease before and after a
      walking exercise. The participants were asked to stop walking when they
      considered themselves "very fatigued." RESULTS: After the exercise-induced
      fatigue, a significant increase in range of motion in pelvis obliquity, hip
      abduction and adduction, and ankle flexion and extension during gait was reported
      along with an increase in stride length variability. Fatigue also reduced the
      knee flexor strength and had a detrimental effect on postural control.
      CONCLUSIONS: Fatigue affects the strength, postural control, and gait of children
      with a neuromuscular disease and could notably increase the risks of falling and
      the occurrence of serious injuries.

PMID- 24743454
TI  - Magnetic resonance imaging of a fibrous band causing true neurogenic thoracic
      outlet syndrome.

PMID- 24743455
TI  - Breast cancer-related lymphedema: a randomized controlled pilot and feasibility
      study.
AB  - OBJECTIVE: Chronic lymphedema occurs frequently in breast cancer patients and is
      associated with significant morbidity and reduced quality-of-life. In this pilot
      study, the authors (1) addressed whether conducting a larger randomized
      controlled trial of aqua lymphatic therapy (ALT) would be feasible and (2)
      estimated the extent to which ALT combined with home-based exercise compared with
      home-based exercise alone would reduce arm disability in patients with breast
      cancer-related lymphedema. DESIGN: Twenty-five women with breast cancer-related
      lymphedema were randomized to either ALT in addition to a home land-based
      exercise program (ALT group; n = 13) or to a home land-based exercise program
      alone (control group; n = 12). The participants were evaluated before and after a
      12-wk intervention period composed of weekly pool exercise sessions. Main outcome
      measures were arm volume, arm disability, pain, and quality-of-life. RESULTS: At
      follow-up, there was no statistical difference between the control and ALT groups
      in any of the outcomes, except for present pain intensity. At the end of the
      study period, there was no change in the lymphedematous limb volume in either
      group. Grip strength was improved in both groups. Only the ALT group showed a
      statistically significant difference with a reduction in pain intensity score and
      arm disability. Furthermore, quality-of-life significantly improved only in the
      ALT group. CONCLUSIONS: Conducting a larger randomized controlled trial would be
      feasible. In comparison with the beginning of the intervention, the participants
      in the ALT group showed significant beneficial changes after 12 wks of treatment,
      whereas the control group did not improve. ALT did not make the lymphedema volume
      worse and therefore may serve as a safe alternative to land-based treatments of
      breast cancer-related lymphedema.

PMID- 24743456
TI  - Impact of habitual exercise on the strength of individuals with myotonic
      dystrophy type 1.
AB  - OBJECTIVE: It remains unclear whether habitual physical activity can attenuate
      the rate of progressive muscle strength loss in individuals with myotonic
      dystrophy type 1 (DM1). The aim of this study was to identify whether there were
      any strength differences between DM1 patients who were habitually active or
      sedentary. DESIGN: Knee extension, handgrip, and elbow flexion quantitative
      strength measurements were investigated in the DM1 patients using isokinetic
      dynamometry. Strength was compared between the patients who followed self
      selected formal exercise plans for at least 1 yr, those who were sedentary
      (controls), and those who initiated or terminated a formal exercise routine.
      RESULTS: Physically active DM1 patients with midrange CTG repeat size (100-500
      CTG repeat sizes) had significantly stronger handgrip and knee extension and
      elbow flexion torques as compared with their sedentary counterparts with the same
      CTG repeat range. The DM1 patients who began a formal exercise routine
      experienced a significant improvement in knee extension torque measurements
      (+24.3%) in comparison with those who were habitually active or sedentary.
      CONCLUSIONS: These data suggest that there is an association between physical
      activity and strength. This may be shown to be a useful tool for the management
      of this condition. Further investigations into the relationships between physical
      exercise, muscle weakness, and genetic factors are needed before evidence-based
      recommendations can be made.

PMID- 24743457
TI  - A description of neck motor performance, neck pain, fatigue, and mental effort
      while driving in a sample with chronic whiplash-associated disorders.
AB  - OBJECTIVE: Individuals with chronic whiplash-associated disorders (WADs) often
      note driving as a difficult task. This study's aims were to (1) compare, while
      driving, neck motor performance, mental effort, and fatigue in individuals with
      chronic WAD against healthy controls and (2) investigate the relationships of
      these variables and neck pain to self-reported driving difficulty in the WAD
      group. DESIGN: This study involved 14 participants in each group (WAD and
      control). Measures included self-reported driving difficulty and measures of neck
      pain intensity, overall fatigue, mental effort, and neck motor performance (head
      rotation and upper trapezius activity) while driving a simulator. RESULTS: The
      WAD group had greater absolute path of head rotation in a simulated city area and
      used greater mental effort (P = 0.04), but there were no differences in other
      measures while driving compared with the controls (all P >= 0.05). Self-reported
      driving difficulty correlated moderately with neck pain intensity, fatigue level,
      and maximum velocity of head rotation while driving in the WAD group (all P <
      0.05). CONCLUSIONS: Individuals with chronic WAD do not seem to have impaired
      neck motor performance while driving yet use greater mental effort. Neck pain,
      fatigue, and maximum head rotation velocity could be potential contributors to
      self-reported driving difficulty in this group.

PMID- 24743458
TI  - Common peroneal nerve palsy caused by compression stockings after surgery.
AB  - Peroneal nerve palsy is one of the more common entrapment neuropathies of the
      lower limb and can be a result of a multitude of causes. Compression stockings
      are commonly used for prophylaxis of deep venous thromboembolism after surgery.
      The entrapment on the head and the neck of the fibula caused by compression
      stockings is uncommon. In this article, the authors report a 46-yr-old male
      patient who was operated on for postauricular squamous cell carcinoma of the
      skin. On the third postoperative day, it was noticed that compression stockings
      had rolled down, and a linear impression mark was observed under its upper edge
      at the proximal part of the left cruris. He had left foot drop and difficulty in
      walking during gait assessment. The needle electromyography confirmed total
      axonal degeneration of the left peroneal nerve with denervation potentials. The
      aim of this report was to emphasize the importance of the size and length of the
      compression stockings and regular skin control in avoiding the risk for peroneal
      nerve palsy. 

PMID- 24743459
TI  - Anterior inferior iliac spine avulsion fracture.

PMID- 24743460
TI  - Upper-limb position sense deficits in adults with cerebral palsy.
AB  - OBJECTIVE: The aim of this study was to examine proprioceptive performance in
      adults with hemiplegic cerebral palsy and the possibility that a home-based
      sensorimotor training program could improve proprioceptive performance. DESIGN:
      This study is a preintervention/postintervention assessment of 12 adults
      participating in a home-based program consisting of targeted unilateral and
      bilateral reaching movements, hand manipulation tasks, tactile discrimination,
      and stereognosis. It did not specifically include proprioceptive tasks. Training
      sessions were 45 mins, 5 days per week, for 8 wks. Limb position sense was
      assessed using three conditions: ipsilateral remembered (same arm used for
      reference and matching targets), contralateral concurrent (reference arm moved
      and held at target position while opposite arm matched reference position), and
      contralateral remembered (reference arm moved to target position and then
      returned to start position before opposite arm matching position). RESULTS: The
      participants demonstrated greater absolute and constant error when the more
      affected arm served as the reference arm, and matching was performed by the less
      affected arm, particularly in the contralateral remembered condition. After
      training, the participants demonstrated less absolute error across matching tasks
      and no change in constant error. CONCLUSIONS: The results suggest an important
      role for the reference arm in bilateral position matching tasks and the potential
      for improved proprioceptive performance after training in movement and unrelated
      sensory tasks.

PMID- 24743461
TI  - Fiber-optic bronchoscopy and volume-cycled mouthpiece ventilation for a patient
      with multiple sclerosis and ventilatory failure.
AB  - Fiber-optic bronchoscopy supported by continuous or bilevel positive airway
      pressure has helped patients with hypoxemic or hypercapnic respiratory failure
      avoid respiratory complications. The authors describe a case of a 57-yr-old man
      with multiple sclerosis with a vital capacity of 250 ml (5% of predicted normal)
      who was using continuous noninvasive intermittent positive pressure ventilatory
      support when he underwent bronchoscopy while receiving continuous noninvasive
      intermittent positive pressure ventilatory support via a 15-mm angled mouthpiece
      interface. He was switched from a nasal to a 15-mm angled mouthpiece interface
      for continuous noninvasive intermittent positive pressure ventilatory support for
      the procedure. Simple mouthpieces may be useful alternatives to other facial
      interfaces for ventilatory support during bronchoscopy because of patient comfort
      and operator convenience. 

PMID- 24743462
TI  - Cancer Functional Assessment Set: a new tool for functional evaluation in cancer.
AB  - OBJECTIVE: The aim of this study was to develop and evaluate the psychometric
      properties of a new measurement tool, the Cancer Functional Assessment Set
      (cFAS). DESIGN: A total of 119 inpatients with cancer participated in this
      prospective cohort study. This study took place in three phases: (1) item
      generation, literature search, and a round-table discussion by 32 rehabilitation
      specialists; (2) item reduction and selection of appropriate items from the first
      item pool; and (3) evaluation of psychometric properties. Concurrent validity
      (Spearman correlation coefficients with existing scales), internal reliability
      (Cronbach coefficient alpha), interrater reliability (weighted kappa statistics
      and intraclass correlation coefficient), cross-validation, and responsiveness
      (standardized response mean values) were examined. RESULTS: The cFAS consisted of
      24 items. Significant correlations were found between the cFAS and existing
      scales. Cronbach alpha for the total score was 0.92. Weighted kappa values for
      each item ranged from 0.74 to 1.00. The intraclass correlation for the total
      score was 0.97. Concurrent validity and internal consistency were similar at two
      different hospitals. The cFAS was more responsive to changes than the other
      tools. CONCLUSIONS: The cFAS has acceptable psychometric properties, supporting
      its broad generalizability. It can be a useful tool in clinical trials and can
      contribute to the development of cancer rehabilitation.

PMID- 24743463
TI  - Interventional spinal procedures in the presence of a Chiari malformation: a
      potential contraindication.
AB  - Although Chiari malformations are much more prevalent than once believed, no
      study has described treatment with an interventional spinal procedure. The
      purpose of this report was to discuss the clinical course of a patient who was
      diagnosed with a Chiari malformation and treated with three cervical epidural
      injections. In 2012, a 50-yr-old woman presented to a neurology clinic with
      chronic suboccipital headaches, diplopia, and increasing numbness/tingling in her
      upper extremities. Magnetic resonance imaging confirmed a type I Chiari
      malformation and a cervical syrinx. The patient was treated with three cervical
      epidural injections, after which her symptoms exacerbated. Consequently, a
      posterior fossa suboccipital craniectomy with C1 laminectomy and excision of
      extradural and intradural adhesions was performed. After surgical intervention,
      notable neurologic improvements were observed. Given the marked worsening of
      symptoms, the present report suggests that interventional spinal procedures may
      be a contraindication in the presence of a Chiari malformation with a syrinx. 

PMID- 24743464
TI  - Effects of vibration on spasticity in individuals with spinal cord injury: a
      scoping systematic review.
AB  - The objective of this systematic review was to evaluate how whole-body vibration
      (WBV) or focal vibration (FV) would change spasticity in individuals with spinal
      cord injury (SCI). A search was conducted of MEDLINE, EMBASE, CINAHL, and
      PsycINFO electronic databases. A hand search was conducted of the bibliographies
      of articles and journals relevant to the research question. The inclusion
      criteria were three or more individuals, 17 yrs or older, with SCI who experience
      spasticity, and WBV or FV application. The evidence level of all ten identified
      studies (195 SCI subjects) was low on the basis of Centre for Evidence Based
      Medicine level of evidence. WBV (n = 1) and FV (n = 9) were applied to assess the
      effects of vibration on different measures of spasticity in individuals with SCI.
      FV application resulted in a short-term spasticity reduction lasting for a
      maximum of 24 hrs. Neurophysiologic measures showed H-reflex inhibition in
      individuals with SCI after FV application. WBV resulted in a decrease in
      spasticity lasting for 6-8 days after the last vibration session. WBV and FV
      might decrease spasticity for a short period, but no evidence-based
      recommendation can be drawn from the literature to guide rehabilitation medicine
      clinicians to manage spasticity with vibration application. 

PMID- 24743465
TI  - Don't put your scar on the vibrating platform.

PMID- 24743466
TI  - Effect of exercise on cancer-related fatigue: a meta-analysis.
AB  - Numerous randomized controlled trials have been conducted to determine efficacy
      of exercise on cancer-related fatigue. However, many trials lacked sufficient
      power to demonstrate significant differences, and little is known about how the
      effect of exercise differs depending on patient- and intervention-level
      characteristics. A meta-analysis was performed to determine whether exercise
      reduces fatigue compared with usual care or nonexercise control intervention in
      patients with cancer. The authors searched Ovid MEDLINE, EMBASE, PsycINFO, The
      Cochrane Central Register of Controlled Trials, and CINAHL. Two authors
      independently extracted the data. Randomized controlled trials comparing exercise
      with control intervention in cancer patients in which fatigue was quantified were
      eligible. Seventy-two randomized controlled trials were identified, 71 in adults
      and 1 in children. Exercise had a moderate effect on reducing fatigue compared
      with control intervention. Exercise also improved depression and sleep
      disturbance. Type of exercise did not significantly influence the effect on
      fatigue, depression, or sleep disturbance. Exercise effect was larger in the
      studies published 2009 or later. There was only one pediatric study. The results
      of this study suggest that exercise is effective for the management of cancer
      related fatigue. 

PMID- 24743467
TI  - Response to letter by Dr Santaeugenia and colleagues.

PMID- 24743468
TI  - Duchenne muscular dystrophy: life prolongation by noninvasive ventilatory
      support.
AB  - OBJECTIVE: American, Japanese, and Canadian centers have demonstrated that
      noninvasive intermittent positive pressure ventilatory support (NVS) can be used
      continuously and in the long-term by people with Duchenne muscular dystrophy as a
      definitive alternative to tracheostomy mechanical ventilation. The aim of this
      study was to report this for the first time in Europe. DESIGN: In this study,
      more than 300 patients with Duchenne muscular dystrophy were followed. End-tidal
      carbon dioxide, oxyhemoglobin saturation, and vital capacity were measured at
      each visit. Of the 300 patients, 79 used NVS for 8 hrs or more per day and 20 of
      these became continuously dependent on NVS. RESULTS: A total of 20 patients have
      continuously depended on NVS for survival, for a total of 336 patient-years, up
      to 16 yrs in one case. Nocturnal NVS was begun for symptomatic hypoventilation
      when the vital capacity had decreased to a mean of 831 +/- 173 ml, and continuous
      dependence on NVS was necessary when the vital capacity had decreased below 297
      +/- 113 ml. CONCLUSIONS: Noninvasive respiratory management can prolong survival
      without resorting to tracheotomy and without hospitalization.

PMID- 24743469
TI  - Relationship of preinjury depressive symptoms to outcomes 3 mos after complicated
      and uncomplicated mild traumatic brain injury.
AB  - OBJECTIVE: This study examines the effect of preinjury depressive symptoms on
      outcomes 3 mos after complicated and uncomplicated cases of mild traumatic brain
      injury. DESIGN: Preinjury depressive symptoms, experienced in the 30 days before
      injury, as measured by retrospective self-report, were assessed within the first
      2 wks after injury. The outcome measures assessed at 3 mos after injury included
      affective/behavioral, cognitive, and physical problems and health-related quality
      of-life. RESULTS: There were 177 patients who completed both the baseline and 3
      mo follow-up interviews. The sample was categorized by severity of depressive
      symptoms in the month before injury as normal, mild, or moderate-severe. Compared
      with those reporting no preinjury depressive symptoms, persons reporting moderate
      severe depressive symptoms had significantly worse outcomes on the Affective and
      Behavioral and the Cognitive subscales of the Head Injury-Family Interview
      Problem Checklist and on the 36-item Short-Form Health Survey Mental Component
      Summary score. The group reporting mild preinjury depressive symptoms scored
      worse on a measure of cognitive symptoms compared with those with no preinjury
      depressive symptoms. There was no interaction between preinjury depressive
      symptoms and severity of the mild traumatic brain injury (complicated or
      uncomplicated) for any of the outcomes. CONCLUSION: Moderate to severe depressive
      symptoms in the month before injury seems to be a possible risk factor for poor
      affective/behavioral, cognitive, and mental health-related quality-of-life
      outcomes at 3 mos after mild traumatic brain injury. Clinicians and researchers
      should consider the impact of preinjury depression on the recovery process to
      provide at-risk patients adequate treatment soon after injury.

PMID- 24743471
TI  - Left atrial appendage closure - new choice for no-option patients with atrial
      fibrillation.
AB  - AIM: Remodeling and impaired blood flow in left atrial appendage (LAA), which
      occurs in patients with atrial fibrillation (AF), may lead to thrombus formation
      and possible thromboembolic complications. Although there are several
      pharmacological antithrombotic possibilities, some patients with several co
      morbidities and contraindications to such treatment cannot be offered any of
      them. Therefore LAA closure systems may be an attractive alternative. We present
      our early experience with two currently available different LAA transcatheter
      closure systems (Watchman and Amplatzer Cardiac Plug). METHODS: Twenty three
      patients (mean age 69.1+/-6.8 years, 12 male) with non-rheumatic AF and high risk
      of thromboembolic complications (CHA2DS2-VASc score >=2 (mean 4.5+/-1.5), who
      could not be treated with the long-term oral anticoagulation because of
      contraindications or significant side effects, were qualified to the LAA closure.
      RESULTS: The Amplatzer Cardiac Plug (St Jude Medical, St Paul, MN, USA) was
      implanted in 7 patients and Watchman Occluder (Boston Scientific, Boston, MA,
      USA) in the other 15 patients. The implantation was not performed in one patient
      as the transoesophageal echocardiography during the procedure revealed a new
      thrombus in LAA. The procedural details and follow-up data are presented. Neither
      severe pericardial effusion nor device related thrombus were observed. In long
      term follow-up transient ischemic attack was noted only in one patient (diagnosed
      with thrombophilia). One patient died 14 months after the procedure due to non
      cardiac reason. CONCLUSION: The LAA occluder implantation seems to be a safe and
      reasonable alternative for oral anticoagulation and should be considered in
      patients with AF who have contraindications or complications of pharmacological
      treatment.

PMID- 24743470
TI  - Timing of neuropeptide coupling determines synchrony and entrainment in the
      mammalian circadian clock.
AB  - Robust synchronization is a critical feature of several systems including the
      mammalian circadian clock. The master circadian clock in mammals consists of
      about 20000 'sloppy' neuronal oscillators within the hypothalamus that keep
      robust time by synchronization driven by inter-neuronal coupling. The complete
      understanding of this synchronization in the mammalian circadian clock and the
      mechanisms underlying it remain an open question. Experiments and computational
      studies have shown that coupling individual oscillators can achieve robust
      synchrony, despite heterogeneity and different network topologies. But, much less
      is known regarding the mechanisms and circuits involved in achieving this
      coupling, due to both system complexity and experimental limitations. Here, we
      computationally study the coupling mediated by the primary coupling neuropeptide,
      vasoactive intestinal peptide (VIP) and its canonical receptor, VPAC2R, using the
      transcriptional elements and generic mode of VIP-VPAC2R signaling. We find that
      synchrony is only possible if VIP (an inducer of Per expression) is released in
      phase with activators of Per expression. Moreover, anti-phasic VIP release
      suppresses coherent rhythms by moving the network into a desynchronous state.
      Importantly, experimentally observed rhythms in VPAC2R have little effect on
      network synchronization, but can improve the amplitude of the SCN network rhythms
      while narrowing the network entrainment range. We further show that these
      findings are valid across several computational network models. Thus, we
      identified a general design principle to achieve robust synchronization: An
      activating coupling agent, such as VIP, must act in-phase with the activity of
      core-clock promoters. More generally, the phase of coupling is as critical as the
      strength of coupling from the viewpoint of synchrony and entrainment. 

PMID- 24743473
TI  - Plastic proteins and monkey blocks: how lentiviruses evolved to replicate in the
      presence of primate restriction factors.

PMID- 24743474
TI  - Conditional reverse tet-transactivator mouse strains for the efficient induction
      of TRE-regulated transgenes in mice.
AB  - Tetracycline or doxycycline (dox)-regulated control of genetic elements allows
      inducible, reversible and tissue specific regulation of gene expression in mice.
      This approach provides a means to investigate protein function in specific cell
      lineages and at defined periods of development and disease. Efficient and stable
      regulation of cDNAs or non-coding elements (e.g. shRNAs) downstream of the
      tetracycline-regulated element (TRE) requires the robust expression of a tet
      transactivator protein, commonly the reverse tet-transactivator, rtTA. Most rtTA
      strains rely on tissue specific promoters that often do not provide sufficient
      rtTA levels for optimal inducible expression. Here we describe the generation of
      two mouse strains that enable Cre-dependent, robust expression of rtTA3,
      providing tissue-restricted and consistent induction of TRE-controlled
      transgenes. We show that these transgenic strains can be effectively combined
      with established mouse models of disease, including both Cre/LoxP-based
      approaches and non Cre-dependent disease models. The integration of these new
      tools with established mouse models promises the development of more flexible
      genetic systems to uncover the mechanisms of development and disease
      pathogenesis. 

PMID- 24743472
TI  - Leishmania-HIV co-infection: clinical presentation and outcomes in an urban area
      in Brazil.
AB  - BACKGROUND: Visceral leishmaniasis (VL) is an emerging condition affecting HIV
      infected patients living in Latin America, particularly in Brazil. Leishmania-HIV
      coinfection represents a challenging diagnosis because the clinical picture of VL
      is similar to that of other disseminated opportunistic diseases. Additionally,
      coinfection is related to treatment failure, relapse and high mortality.
      OBJECTIVE: To assess the clinical-laboratory profile and outcomes of VL-HIV
      coinfected patients using a group of non HIV-infected patients diagnosed with VL
      during the same period as a comparator. METHODS: The study was conducted at a
      reference center for infectious diseases in Brazil. All patients with suspected
      VL were evaluated in an ongoing cohort study. Confirmed cases were divided into
      two groups: with and without HIV coinfection. Patients were treated according to
      the current guidelines of the Ministry of Health of Brazil, which considers
      antimony as the first-choice therapy for non HIV-infected patients and recommends
      amphotericin B for HIV-infected patients. After treatment, all patients with CD4
      counts below 350 cells/mm3 received secondary prophylaxis with amphotericin B.
      RESULTS: Between 2011 and 2013, 168 patients with suspected VL were evaluated, of
      whom 90 were confirmed to have VL. In total, 51% were HIV coinfected patients (46
      patients). HIV-infected patients had a lower rate of fever and splenomegaly
      compared with immunocompetent patients. The VL relapse rate in 6 months was 37%
      among HIV-infected patients, despite receiving secondary prophylaxis. The overall
      case-fatality rate was 6.6% (4 deaths in the HIV-infected group versus 2 deaths
      in the non HIV-infected group). The main risk factors for a poor outcome at 6
      months after the end of treatment were HIV infection, bleeding and a previous VL
      episode. CONCLUSION: Although VL mortality rates among HIV-infected individuals
      are close to those observed among immunocompetent patients treated with
      amphotericin B, HIV coinfection is related to a low clinical response and high
      relapse rates within 6 months.

PMID- 24743475
TI  - [Aortic valve replacement after percutaneous transcatheter aortic valvuloplasty
      for severe aortic stenosis].
AB  - BACKGROUND: Aortic valve replacement( AVR) is a definitive treatment in patients
      with severely calcified aortic stenosis (AS). However, elderly patients with
      multiple comorbidities are considered to be unsuitable for AVR. Percutaneous
      transcatheter aortic valvuloplasty( PTAV) has been performed as a palliative
      option to relieve symptoms or to be a bridge use toward definitive therapy. This
      study aimed to examine the effectiveness and clinical outcome of surgical AVR
      subsequent to PTAV. PATIENTS AND METHODS: Since 2010, 5 symptomatic patients have
      undergone AVR after PTAV in our institution. PTAV was performed as a bridge to
      definitive AVR in 2 patients. Other 2 patients developed symptomatic aortic valve
      restenosis during a follow-up, and required AVR. In the last patient,AVR was
      carried out after successful noncardiac surgery subsequent to PTAV. RESULTS: AVR
      improved cardiac hemodynamics in all patients. There was no operative death.
      Postoperative course was uneventful and all patients were discharged on foot
      except for 1 patient in whom metastatic liver tumor from advanced gastric cancer
      was noted. CONCLUSION: AVR might be performed safely even in high-risk patients
      with the history of PTAV. PTAV is useful as a palliation or a bridge to
      definitive therapy for treatment of patients with severe AS unsuitable for
      surgery.

PMID- 24743476
TI  - [Pulmonary blood flow measurement using magnetic resonance imaging (MRI) without
      contrast medium;comparison of phase contrast MRI and perfusion-ventilation
      scintigraphy].
AB  - To define the accuracy of pulmonary arterial blood flow (PA-flow) measured by
      phase contrast magnetic resonance imaging (PC-MRI), we compared the PA-flow data
      of PC-MRI with the data of perfusion-ventilation lung scintigraphy. Eighteen
      patients who preoperatively underwent PA-flow measurement using PC-MRI and
      perfusion-ventilation lung scintigraphy were evaluated. The PA-flow (cm3/sec) of
      MRI was calculated by multiplying maximum velocity (cm/sec) by region of interest
      (ROI) area (cm2) of measured main pulmonary artery using phase contrast method.
      The left to right ratio (R/L ratio) of PA-flow measured by PC-MRI was compared
      with the R/L ratios of the date of perfusion-ventilation lung scintigraphy. The
      R/L ratios of PC-MRI and perfusion lung scintigraphy were 1.43 +/- 1.07 and 1.35
      +/- 0.82, respectively. Both ratios showed excellent correlation( y=-0.50+1.30x,
      r=0.99,p<0.001). The R/L ratios of PC-MRI also approximated to those of perfusion
      lung scintigraphy in the patients with a past history of lung resection, even if
      their R/L ratios of perfusion lung scintigraphy differed from those of
      ventilation lung scintigraphy. These results revealed that the PA-flow could be
      accurately measured by PC-MRI without contrast medium and nuclear medicine
      instruments. 

PMID- 24743477
TI  - [Aortic valve replacement for recurrent aortic stenosis after percutaneous
      transluminal balloon aortic valvuloplasty( PTAV) in a cancer patient].
AB  - We report a case of aortic valve replacement( AVR) for recurrent aortic
      stenosis(AS) after percutaneous transluminal balloon aortic valvuloplasty( PTAV)
      in a patient with left renal pelvis carcinoma. A 65-year-old female had been
      suffering from shortness of breath and syncope due to severe AS. She was
      considered to be a candidate for AVR. Preoperative examination revealed advanced
      left renal pelvis carcinoma that was a critical comorbidity for AVR.
      Ureteronephrectomy was also considered to be a contraindication. Despite
      conservative treatment, her condition was deteriorated. Emergency PTAV was
      performed when she was transferred to our hospital with circulatory shock. Her
      symptoms were ameliorated and left ureteronephrectomy was conducted 8 month after
      the PTAV. She was readmitted to our hospital 16 month after the PTAV and AVR was
      performed successfully.Antegrade transseptal PTAV is a very useful palliative
      therapy for AS with severe comorbidities as a bridge to surgery. 

PMID- 24743478
TI  - [Retrograde Stanford type A aortic dissection treated by thoracic endo-vascular
      aortic repair (TEVAR) after ascending aortic replacement].
AB  - A 77-year-old woman was admitted to a hospital with complaints of back pain,
      nausea and vomiting for 4 days. She underwent enhanced aortic computed tomography
      (CT) and was diagnosed with Stanford type A acute aortic dissection. Then she was
      transferred to our hospital. CT showed aortic dissection spreading from the
      ascending aorta up to the abdominal aorta and an intimal tear located at the
      descending thoracic aorta. Although the false lumen of the ascending aorta was
      thrombosed, emergency ascending aorta replacement and aortic valve replacement
      were performed, because pericardial effusion and severe aortic regurgitation were
      found by echocardiography. Postoperative enhanced CT showed an intimal tear and
      residual flow in the false lumen from the distal arch to the descending aorta. So
      an additional thoracic endo-vascular aortic repair (TEVAR) procedure was
      performed to close the entry tear 20 days after the 1st operation. She
      uneventfully left our hospital on the 15th postoperative day. 

PMID- 24743479
TI  - [Pulmonary aspergillosis associated with empyema due to Eikenella corrodens].
AB  - A 74-year-old female had previously undergone a left upper lobectomy and received
      radiotherapy for squamous cell carcinoma of the lung in 2002. She was admitted to
      our hospital because of left pulmonary aspergillosis in 2011. We performed left
      completion pneumonectomy and decortications. After the operation, Eikenella
      corrodens was isolated from pleural effusion. She was therefore diagnosed as
      having simultaneous empyema due to Eikenella corrodens, and continued to have
      antibiotic treatment. Wound dehiscence caused by malnutrition occurred
      postoperatively, but was healed by peroral nutritional support. She was
      discharged 78 days after the operation without recurrence of pulmonary
      aspergillosis and empyema for 23 months. 

PMID- 24743480
TI  - [Effectiveness of tolvaptan for postoperative heart failure in a patient with
      combined valvular disease and pulmonary hypertension].
AB  - We report a case of a 60-year-old man with postoperative congestive heart
      failure( CHF) successfully treated with tolvaptan. The patient was diagnosed with
      pulmonary hypertension due to mitral stenosis and regurgitation combined with
      tricuspid regurgitation. He underwent mitral and tricuspid valvuloplasty. His
      postoperative course was uneventful until CHF symptoms secondary to volume
      overload appeared on the 4th day. Congestion with pulmonary hypertension was
      treated with 0.042 MUg/kg/min of intravenous human atrial natriuretic peptide
      (hANP). His condition improved, and on the 11th postoperative day, he was weaned
      off hANP;oral administration of 40 mg per day of furosemide was initiated.
      However, 2 days after discontinuation of intravenous hANP, CHF recurred and serum
      sodium decreased to 128 mEq/l. Oral tolvaptan 7.5 mg per day was added to the
      furosemide, and CHF and hyponatremia subsequently improved. In this case, oral
      tolvaptan was effective for the treatment of refractory CHF with pulmonary
      hypertension after cardiac surgery. 

PMID- 24743481
TI  - [Endoscopic saphenous vein harvesting with non-disposable device].
AB  - Endoscopic vein harvesting (EVH) for coronary artery bypass grafting has been
      proved to be effective in reduced wound complications, without compromising long
      term mortality or composite of death, myocardial infarction and repeat
      revascularization. However, only disposable devices that are costly and raise
      environmental problems, have been obtained on the market in Japan. Now, a non
      disposable device for EVH is available. With this equipment, a 50 cm-long great
      saphenous vein can be obtained with a single 3 cm-long incision. We demonstrate
      how to use this device and show its tips and pitfall. 

PMID- 24743482
TI  - [Primary cardiac angiosarcoma in the right atrium with cardiac tamponade].
AB  - Primary cardiac angiosarcoma is very rare with an incidence of 0.0017~0.19% in
      collected autopsy series, and its prognosis has been reported as being extremely
      poor( average survival of 6~9 months). A 56-year-old man was referred to our
      hospital with cardiac tamponade caused by right atrial angiosarcoma, after
      initially being misdiagnosed as acute type A dissection. Echocardiography and
      chest computed tomography (CT) revealed a pedunculated tumor with a broad base
      which was originating from the right atrial wall and extended into atrio
      ventricular (AV) groove. The tumor was completely resected, and a bovine
      pericardium patch was used for cardiac reconstruction. Histological examination
      showed angiosarcoma and a sign of radical excision. The patient, who made an
      uneventful recovery,was given postoperative radiotherapy and chemotherapy. He
      died of multiple systemic metastases 14 months postoperatively despite of
      multidisciplinary treatment. We discuss the therapeutic strategies available for
      this highly malignant cardiac tumor. 

PMID- 24743483
TI  - [Aortic regurgitation in a patient with polyarteritis nodosa].
AB  - Polyarteritis nodosa (PN) is vasculitis of small- to medium-sized arteries. A 57
      year-old woman with PN developed aortic valve regurgitation. Aortic valve
      replacement (AVR) was performed. We found inflammatory change of the ascending
      aorta which was rarely involved in PN. Abnormal thickness of the aortic wall was
      recognized during operation, which had not been detected by preoperative computed
      tomography. Perioperative course was uneventful, and the patient underwent anti
      inflammatory therapy after the operation. No perivalvular leakage has been
      detected for 3 years since AVR. We should consider the possibility of aortitis,
      when cardiovascular operations are performed in patients with vasculitis for
      small- to medium-sized arteries. 

PMID- 24743484
TI  - [Extralobar pulmonary sequestration mimicking posterior mediastinal tumor].
AB  - The case was 13-year-old man. He visited local hospital due to high fever and
      back pain. He was diagnosed as acute pleuritis based on a chest computed
      tomography( CT) scan and referred to our hospital for treatment. Chest CT scan
      revealed a round shaped mass with clear margin at the left vertebrophrenic angle.
      A neurogenic posterior mediastinal tumor was suspected. Thoracoscopic surgery
      revealed that the mass had 2 thin string-like structures connecting to the
      descending aorta, and was suspected to be a pulmonary sequestration. The resected
      tumor was pathologically confirmed to be an extralobar pulmonary sequestration
      most of which was hemorrhagic necrosis caused by arterial infarction.

PMID- 24743485
TI  - [Surgically treated desmoid tumor of the chest wall which located at the previous
      thoracotomy site].
AB  - Desmoid tumor is a soft-tissue tumor of unknown cause. Since recurrence sometimes
      occurs even with complete resection, careful consideration of which portions to
      resect and close postoperative followup are recommended. Seventeen months after
      undergoing a right upper lobectomy for primary lung adenocarcinoma, a 65-year-old
      female patient experienced pleural tumor which located at the previous
      thoracotomy site, as revealed by chest X-ray and computed tomography (CT). While
      needle aspiration biopsy revealed no malignancy, recurrence of the cancer could
      not be ruled out clinically. The tumor was resected with chest wall and lung and
      the histopathological diagnosis was desmoid tumor. This case demonstrates the
      importance of conducting differential diagnosis with recurrence or desmoid tumor
      after operation to treat lung cancer. Five years after resection of the desmoid
      tumor, no recurrence is observed. 

PMID- 24743486
TI  - [Mitral annuloplasty and coronary artery bypass grafting (CABG) with on-pump
      beating via left thoracotomy for ischemic mitral valve regurgitation with patent
      internal thoracic artery( ITA) grafts after CABG;report of a case].
AB  - A 69-year-old man was admitted with progressive congestive heart failure due to
      ischemic mitral valve regurgitation. He had previously undergone coronary artery
      bypass grafting( CABG) using bilateral internal thoracic arteries( ITAs) and
      saphenous vein grafts( SVG). An angiogram revealed patent bilateral ITAs and
      stenosis of the SVG affecting the left circumflex (LCX) branch, which persisted
      despite repeated catheter intervention. Patent ITA grafts were located
      immediately beneath the sternum. We performed a mitral annuloplasty and CABG( SVG
      LCX) simultaneously with on-pump beating via left thoracotomy. Postoperative
      course was uneventful and mitral valve regurgitation disappeared with patent SVG
      LCX. 

PMID- 24743487
TI  - [Successful treatment of a case of chylothorax, manifesting as a complication
      following surgical treatment of coarctation of the aorta, by using octreotide
      acetate; report of a case].
AB  - Chylothorax - a serious postoperative complication of thoracic surgery - is
      associated with high morbidity and mortality, and re-exploration is required in
      many such cases. A 33-year-old male patient had undergone an extra-anatomic
      bypass for the treatment of coarctation of the aorta. Persistent chylothorax
      developed as a complication postoperatively. Octreotide acetate was administered
      11 days postoperatively, which resolved the chylothorax without the need for
      surgical intervention. The patient was discharged from our hospital without any
      complications at 40 days postoperatively. In the present report, we describe this
      case and a provide a review of the literature. 

PMID- 24743488
TI  - [Traumatic type A dissection with acute pericarditis 6 weeks after blunt trauma;
      report of a case].
AB  - A 38-year-old man presented with typical symptom of acute pericarditis and
      chronic cardiac tamponade 6 weeks after blunt trauma. Follow-up computed
      tomography after 2 weeks revealed a localized dissection at the proximal part of
      the ascending aorta. This is a rare case of chronic Stanford type A aortic
      dissection after blunt trauma, a diagnosis of which was established later with
      consistent suspicion and repeated examination by computed tomography. 

PMID- 24743489
TI  - [Pacemaker infection in a child; report of a case].
AB  - In the treatment for pacemaker infection, removal of infected devices and
      intensive antibiotics therapy are in principle and new devices should be
      implanted apart from the infected site. However, there are some problems in the
      case of children:it is not easy to remove infected devices because epicardial
      leads are often used for them. If endocardial leads are chosen as a new system,
      extension of the lead would be concerned with their growth. We report a pediatric
      case of infection of pacemaker using epicardial leads. It was difficult to cure
      infection by repeated local treatment leaving epicardial leads and antibiotics
      therapy was obliged to continue for 9 years to keep infection under control.
      After growing up, we implanted endocardial leads for her and removed infected
      devices to cure infection completely. 

PMID- 24743490
TI  - [Papillary fibroelastoma attached to the underside of the aortic valve; report of
      a case].
AB  - We report a case of papillary fibroelastoma of the aortic valve. A 72-year-old
      man was referred to our hospital with cardiac tumor incidentally detected by
      transthoracic echocardiography. Transesophageal echocardiography showed a mobile
      tumor on the ventricular side of the aortic valve. We performed semi-emergency
      surgery and resected the tumor with a blade to prevent embolism. Pathologic
      findings revealed papillary fibroelastoma. The postoperative course was
      uneventful, and the patient was discharged 10 days arter surgery. Follow-up
      transthoracic echocardiography has not shown any evidence of local recurrence. 

PMID- 24743491
TI  - [Marginal zone lymphoma of mucosa-associated lymphoid tissue of the parietal
      pleura; report of a case].
AB  - An 76-year-old man was referred to our hospital due to right hydrothorax. The
      diffuse thickening of parietal pleura with increased fluoro-2-deoxy-D-glucose
      (FDG) uptake was noted by computed tomography (CT) and positron emission
      tomography (PET). Surgical biopsy was performed and the tumor was diagnosed as
      mucosal associated lymphoid tissue (MALT) lymphomas of parietal pleura origin by
      pathology. Complete remission was achieved by postoperative chemotherapy (R
      CHOP), and the patient is now alive without recurrence.

PMID- 24743492
TI  - [Bronchial hamartoma in subsegmental bronchus; report of a case].
AB  - We report a rare surgical case of a bronchial hamartoma in subsegmental bronchus.
      A 70-year-old man was incidentally pointed out an abnormal chest shadow without
      any complaints. Chest computed tomography revealed a round nodule with diameter
      of 15 mm in the right upper lobe. The bronchoscopic examination revealed complete
      obstruction of right B2a by the tumor. Right S2 segmentectomy was done to make a
      definite diagnosis and to prevent possible obstructive pneumonia.
      Histopathological examination revealed that the tumor was a benign cartilage
      bronchial hamartoma. 

PMID- 24743493
TI  - Resistance to erythropoiesis stimulating agents in patients treated with online
      hemodiafiltration and ultrapure low-flux hemodialysis: results from a randomized
      controlled trial (CONTRAST).
AB  - Resistance to erythropoiesis stimulating agents (ESA) is common in patients
      undergoing chronic hemodialysis (HD) treatment. ESA responsiveness might be
      improved by enhanced clearance of uremic toxins of middle molecular weight, as
      can be obtained by hemodiafiltration (HDF). In this analysis of the randomized
      controlled CONvective TRAnsport STudy (CONTRAST; NCT00205556), the effect of
      online HDF on ESA resistance and iron parameters was studied. This was a pre
      specified secondary endpoint of the main trial. A 12 months' analysis of 714
      patients randomized to either treatment with online post-dilution HDF or
      continuation of low-flux HD was performed. Both groups were treated with
      ultrapure dialysis fluids. ESA resistance, measured every three months, was
      expressed as the ESA index (weight adjusted weekly ESA dose in daily defined
      doses [DDD]/hematocrit). The mean ESA index during 12 months was not different
      between patients treated with HDF or HD (mean difference HDF versus HD over time
      0.029 DDD/kg/Hct/week [-0.024 to 0.081]; P = 0.29). Mean transferrin saturation
      ratio and ferritin levels during the study tended to be lower in patients treated
      with HDF (-2.52% [-4.72 to -0.31]; P = 0.02 and -49 ng/mL [-103 to 4]; P = 0.06
      respectively), although there was a trend for those patients to receive slightly
      more iron supplementation (7.1 mg/week [-0.4 to 14.5]; P = 0.06). In conclusion,
      compared to low-flux HD with ultrapure dialysis fluid, treatment with online HDF
      did not result in a decrease in ESA resistance. TRIAL REGISTRATION:
      ClinicalTrials.gov NCT00205556.

PMID- 24743494
TI  - Kinetics of leptin binding to the Q223R leptin receptor.
AB  - Studies in human populations and mouse models of disease have linked the common
      leptin receptor Q223R mutation to obesity, multiple forms of cancer, adverse drug
      reactions, and susceptibility to enteric and respiratory infections.
      Contradictory results cast doubt on the phenotypic consequences of this variant.
      We set out to determine whether the Q223R substitution affects leptin binding
      kinetics using surface plasmon resonance (SPR), a technique that allows sensitive
      real-time monitoring of protein-protein interactions. We measured the binding and
      dissociation rate constants for leptin to the extracellular domain of WT and
      Q223R murine leptin receptors expressed as Fc-fusion proteins and found that the
      mutant receptor does not significantly differ in kinetics of leptin binding from
      the WT leptin receptor. (WT: ka 1.76*106+/-0.193*106 M-1 s-1, kd 1.21*10-4+/
      0.707*10-4 s-1, KD 6.47*10-11+/-3.30*10-11 M; Q223R: ka 1.75*106+/-0.0245*106 M-1
      s-1, kd 1.47*10-4+/-0.0505*10-4 s-1, KD 8.43*10-11+/-0.407*10-11 M). Our results
      support earlier findings that differences in affinity and kinetics of leptin
      binding are unlikely to explain mechanistically the phenotypes that have been
      linked to this common genetic variant. Future studies will seek to elucidate the
      mechanism by which this mutation influences susceptibility to metabolic,
      infectious, and malignant pathologies. 

PMID- 24743496
TI  - Studies of a prototype linear stationary x-ray source for tomosynthesis imaging.
AB  - A prototype linear x-ray source to implement stationary source-stationary
      detector tomosynthesis (TS) imaging has been studied. Potential applications
      include human breast and small animal imaging. The source is comprised of ten x
      ray source elements each consisting of a field emission cathode, electrostatic
      lens, and target. The electrostatic lens and target are common to all elements.
      The source elements form x-ray focal spots with minimum diameters of 0.3-0.4 mm
      at electron beam currents of up to 40 mA with a beam voltage of 40 kV. The x-ray
      flux versus time was quantified from each source. X-ray bremsstrahlung spectra
      from tungsten targets were produced using electron beam energies from 35 to 50
      keV. The half-value layer was measured to be 0.8, 0.9, and 1.0 mm, respectively,
      for the 35, 40, and 45 kV tube potentials using the tungsten target. The
      suppression of voltage breakdown events, particularly during source operation,
      and the use of a modified form of the standard cold-cathode geometry, enhanced
      source reliability. The prototype linear source was used to collect tomographic
      data sets of a mouse phantom using digital TS reconstruction methods and
      demonstrated a slice-sensitivity profile with a full-width-half-maximum of 1.3
      mm. Lastly, preliminary studies of tomographic imaging of flow through the mouse
      phantom were performed. 

PMID- 24743497
TI  - Corrigendum.
AB  - KINEMATIC MODELLING OF A ROBOTIC GAIT DEVICE FOR EARLY REHABILITATION OF WALKING:
      J Fang, H Gollee, S Galen, D B Allan, B A Conway and A Vuckovic The authors would
      like to bring attention to the error published in "Kinematic modelling of a
      robotic gait device for early rehabilitation of walking", Proceedings of the
      IMechE Part H: Journal of Engineering in Medicine, 2011, Vol. 225(12), pp1177
      1187, doi 10.1177/0954411911424976.

PMID- 24743498
TI  - Removal of emulsified oil from water by fruiting bodies of macro-fungus
      (Auricularia polytricha).
AB  - The aim of this study was to investigate the feasibility of utilizing the
      fruiting bodies of a jelly macro-fungus Auricularia polytricha as adsorbents to
      remove emulsified oil from water. The effects of several factors, including
      temperature, initial pH, agitation speed, and adsorbent dosage, were taken into
      account. Results showed that the optimized conditions for adsorption of A.
      polytricha were a temperature of 35 degrees C, pH of 7.5, and agitation speed of
      100 rpm. The adsorption kinetics were characterized by the pseudo-first order
      model, which showed the adsorption to be a fast physical process. The Langmuir
      Freundlich isotherm described the adsorption very well and predicted the maximum
      adsorption capacity of 398 mg g-1, under optimized conditions. As illustrated by
      scanning electron micrographs, the oil particles were adsorbed onto the hairs
      covering the bottom surface and could be desorbed by normal temperature
      volatilization. The material could be used as an emulsified oil adsorbent at
      least three times, retaining more than 95% of the maximum adsorption capacity.
      The results demonstrated that the fruiting bodies of A. polytricha can be a
      useful adsorbent to remove emulsified oil from water. 

PMID- 24743499
TI  - Preoperative model for end-stage liver disease score as a predictor for
      posthemihepatectomy complications.
AB  - BACKGROUND: As diagnostic techniques advance and surgical outcomes improve, the
      rate of utilization of liver hemihepatectomy for various indications will
      continue to increase. OBJECTIVES: To explore the preoperative predictors of liver
      hemihepatectomy postoperative complications. PATIENTS AND METHODS: This study
      included retrospective analysis of the clinical data of patients who underwent
      either liver hemihepatectomy or extended hemihepatectomy at Georg August
      University Hospital-Goettingen for the period 2002-2012. The outcomes were either
      postoperative complications or death of the patient (within 3 months from the end
      of the operation). Modified classification of surgical complications was adopted
      in the current study. The preoperative model for end-stage liver disease (MELD)
      score, aspartate aminotransferase, creatinine, international normalized ratio,
      and bilirubin in addition to the demographic characteristics of the patients and
      intraoperative blood loss were analyzed as predictive for postliver
      hemihepatectomy complications. RESULTS: The study included 144 patients who
      underwent liver hemiheptectomy or extended hemihepatectomy through the study
      period (2002-2012). Postoperative complications were reported among patients out
      of 144 (52.1%). The most frequent complications were pleural effusion (26.7%),
      biliary leakage (21.3%), wound dehiscence (13.3%), ascites, and intra-abdominal
      abscess (6.7%). Death was reported among six patients of those who developed
      complications (8%). There were four cases of hepatic cirrhosis (one macroscopic
      and three microscopic). Two of the microscopic cases had no postoperative
      complications (grade 1), whereas one case had grade 3a and the macroscopic case
      had postoperative complication grade 1. Their MELD scores ranged between 6 and 10
      preoperatively. The association between preoperative MELD score and development
      of posthemihepatetomy was statistically significant, P=0.002. Death was reported
      in six cases, yielding a mortality rate of 4.17%. MELD score preoperatively was
      the only significant predictor for postoperative complications. CONCLUSION: The
      rate of complications following hemihepatectomy remains high, with 52.1% of the
      patients in the current study having at least one complication as all of our
      patients underwent either hemihepatectomy or extended hemihepatectomy. A 4.17%
      mortality rate has been reported. A higher preoperative MELD score is the only
      significant predictor for the development of posthemihepatectomy complications.

PMID- 24743500
TI  - Holes in gastric mucosa in upper gastrointestinal endoscopy.
AB  - Gastritis cystica profunda (GCP) is a rare disease that shows multiple cystic
      gastric glands dispersed within the submucosa of the stomach. GCP occurs most
      commonly in patients who have undergone previous gastric surgery and presents as
      subepithelial tumor or a polypoid lesion. Here, we report the case of GCP in a 79
      year-old patient who had undergone Billroth II gastric resection. During upper
      gastrointestinal endoscopy multiple lesions like tiny holes in the mucosa were
      observed. Endoscopic ultrasound showed cystic structures in the gastric
      submucosa. Biopsies finally proved the dispersed mucosal glands in the submucosa,
      which are pathognomonic for GCP. So far, in all published cases, GCP presented as
      polypoid lesions with no mucosal damage in upper gastrointestinal endoscopy. It
      is for the first time that GCP has been diagnosed with cystic lesions connected
      to the gastric lumen with a porus in each of the cysts. 

PMID- 24743501
TI  - Long-term treatment outcome of patients with gastric vascular ectasia treated
      with argon plasma coagulation.
AB  - BACKGROUND: Gastric vascular ectasia (VE) is an uncommon cause of upper
      gastrointestinal bleeding. Long-term data on the efficacy of argon plasma
      coagulation (APC) for the treatment of gastric VE are lacking. METHODS: We
      retrospectively identified consecutive patients, between January 2005 and
      December 2010, treated with APC for an index diagnosis of gastric VE. Clinical
      and endoscopic features and APC treatment success were recorded. Treatment
      success was determined by resolution of symptoms and stabilization of the
      hemoglobin level at 30% above baseline. RESULTS: A total of 62 patients [28
      (45.2%) male] with a mean age of 72.6 +/- 12.8 years, who had undergone 159 upper
      endoscopies (mean 2.6, range 1-10), including 140 APC sessions (mean 2.3, range 1
      10), were identified. The duration of follow-up was 46.9 +/- 26.5 months.
      Treatment success was achieved in 16 (25.8%) patients. Predictors of success
      included older age, focal pattern, lack of comorbid liver failure or collagen
      vascular disease, use of antiplatelet or anticoagulant drugs, and lower baseline
      hemoglobin level. Of the patients, 26 (41.9%) died during follow-up. CONCLUSION:
      APC is safe and effective for the initial management of gastric VE; however, most
      patients do not experience long-term resolution of upper gastrointestinal
      bleeding and anemia.

PMID- 24743502
TI  - Treatment of large colorectal neoplasms by endoscopic submucosal dissection: a
      European single-center study.
AB  - OBJECTIVE: Endoscopic submucosal dissection (ESD) has a high curative resection
      rate for gastrointestinal mucosal lesions, but is not used widely in Europe
      because of a high complication rate and a long learning curve. This study
      analyzed the ESD learning curve at a single European treatment center. MATERIALS
      AND METHODS: ESD and hybrid-ESD (hESD) procedures were used to treat large
      colonic lesions that could not be resected in one piece by other endoscopic
      methods. Procedure duration and speed, and en-bloc, complete (R0) resection, and
      complication rates were analyzed. RESULTS: Fifty-three patients underwent ESD (37
      pure ESD, 16 hESD), most with rectal lesions (n=34, 64.2%). The mean lesion
      diameter was 3.7 +/- 1.1 cm2 (range 2.0-7.0 cm), the median procedure duration
      was 70.0 min [interquartile range (IQR) 31.0-113.0 min], and the median treatment
      speed was 0.086 cm2/min (IQR 0.055-0.152). En-bloc and R0 resection rates were
      86.5% (32/37) and 81.1% (30/37), respectively. Procedure speed increased
      significantly after about 25 cases (P=0.0313). The median hESD procedure
      treatment speed was 0.159 cm/min (n=16, IQR 0.094-0.193), which was better than
      with classical ESD (P=0.04). The hESD en-bloc and R0 resection rates were
      comparable to those of classical ESD (P>0.05). The only complication was
      bleeding, 5.7% (3/53); no perforation occurred. Recurrence was detected during
      follow-up (median 30.0 months, IQR 12-48) in one patient (1.7%). CONCLUSION: ESD
      is useful and safe for resection of large colorectal polyps, and procedure speed
      increased considerably after 25 procedures. hESD was faster than ESD, with a high
      therapeutic resection rate.

PMID- 24743503
TI  - Three-dimensional high-resolution anorectal manometry in the diagnosis of
      paradoxical puborectalis syndrome compared with healthy adults: a retrospective
      study in 79 cases.
AB  - OBJECTIVES: The aim of this study is to evaluate the three-dimensional anorectal
      pressure topography of normal healthy adults and patients with paradoxical
      puborectalis syndrome (PPS) using a novel three-dimensional high-resolution
      manometry (3D-HRM) of the anorectum. METHODS: The 3D-HRM probe has a 6.4 cm long
      sensing segment that is composed of 256 independent pressure transducers around
      its circumference. It generates a 3D pressure topographic profile of the
      anorectum. We evaluated 41 women and 38 men with PPS (median age 52 years), and
      compared them with 37 women and 34 men who were healthy (median age 51 years).
      The three-dimensional anorectal pressure topography was evaluated at rest, and
      during squeeze, stimulated defecation, and balloon inflation. RESULTS: Maximum
      resting pressure, mean resting pressure, high pressure zone length, and residual
      anal pressure were significantly higher in patients with PPS compared with
      healthy adults (P<0.01 each). The rectoanal pressure differential was
      significantly lower in the PPS patients compared with healthy adults (P<0.05).
      There was a characteristic purple high-pressure area in the posterior wall of the
      pressure cylinder of patients with PPS during stimulated defecation that was
      absent in healthy adults. The longest diameter and widest diameter of this purple
      high-pressure area were 1.71 +/- 0.25 and 1.07 +/- 0.14 cm. The maximum, mean,
      and minimum pressures of the posterior distal pressure zone were significantly
      higher in patients with PPS (270.1 +/- 8.2, 152.7 +/- 4.8, and 51.9 +/- 2.7 mmHg,
      respectively) compared with healthy adults (168.5 +/- 11.1, 88.0 +/- 5.9, and
      30.7 +/- 2.8 mmHg, respectively) (P<0.01). CONCLUSION: Using the 3D-HRM
      technique, the increase in the resting pressure and residual anal pressure and
      decrease in the rectoanal pressure differential in patients with PPS compared
      with healthy adults further indicated the mechanism of this disease. Unlike
      traditional manometry, the 3D-HRM technique could find, locate, and evaluate the
      scope and the pressure of the paradoxical contraction of puborectalis muscle,
      which further indicates the value of manometry in terms of diagnosis.

PMID- 24743504
TI  - Pentoxifylline for the treatment of nonalcoholic fatty liver disease: a meta
      analysis of randomized double-blind, placebo-controlled studies.
AB  - AIMS: Pentoxifylline has been used to treat nonalcoholic fatty liver diseases
      (NAFLDs) due to its anti-tumor necrosis factor-alpha effects. We conducted a meta
      analysis of randomized, double-blinded, placebo-controlled trials to investigate
      the effect of pentoxifylline on the biochemical and histological parameters of
      NAFLD patients. MATERIALS AND METHODS: A comprehensive literature search was
      conducted in the database including PubMed, Embase, ISI web of knowledge, the
      Cochrane Library, and Google Scholar to identify randomized, double-blind,
      placebo-controlled clinical trials about the effects of pentoxifylline on NAFLD.
      The pooled weighted mean difference (WMD) with 95% confidence interval (CI) was
      calculated to compare the effects of pentoxifylline and placebo. RESULTS: Five
      well-designed studies were retrieved. Pooled results showed that pentoxifylline
      significantly reduced the serum alanine transaminase activity (WMD=-27.97; 95%
      CI: -42.59, -13.34) and aspartate transaminase activity (WMD=-13.97; 95% CI: 
      23.31, -4.63) in NAFLD patients compared with placebo. In addition,
      pentoxifylline significantly improved steatosis (WMD=-0.68; 95% CI: -1.01, 
      0.34), lobular inflammation (WMD=-0.49; 95% CI: -0.86, -0.12), and fibrosis (WMD=
      0.60; 95% CI: -0.99, -0.21). Furthermore, pentoxifylline also led to significant
      reduction in BMI (WMD=-0.51; 95% CI: -0.96, -0.06) and fasting glucose (WMD=
      8.97; 95% CI: -14.52, -3.42), but did not significantly affect the serum tumor
      necrosis factor alpha and adiponectin levels when compared with placebo.
      CONCLUSION: Pentoxifylline could reduce the aminotransferase activities and
      improve the histological parameters in NAFLD patients. Large well-designed,
      randomized, placebo-controlled studies are needed to confirm these results.

PMID- 24743505
TI  - Diagnostic capabilities of high-definition white light endoscopy for the
      diagnosis of gastric intestinal metaplasia and correlation with histologic and
      clinical data.
AB  - OBJECTIVE: The aim of this study was the evaluation of the diagnostic accuracy of
      a specific high-definition white light endoscopy (HD-WLE) system for the optical
      recognition of intestinal metaplasia (IM) and the assessment of its correlation
      with histologic and clinical data. METHODS: A total of 234 patients undergoing
      upper gastrointestinal endoscopy in an outpatient endoscopy suite for various
      indications were prospectively enrolled in this cross-sectional study. Gastric IM
      was diagnosed on the basis of three mucosal patterns identified using HD-WLE in a
      per-patient analysis. Histological evaluation was used as the gold standard, and
      special staining was conducted for subtyping of IM. Main outcome measurements
      were sensitivity, specificity, and likelihood ratio of HD-WLE and secondary
      associations with histologic and clinical data. RESULTS: IM was found in 63/234
      (27%) patients and low-grade dysplasia in 6/63 patients (9.5%). Sensitivity,
      specificity, accuracy, and likelihood ratio of all mucosal patterns were 74.6,
      94, 88% and 13, respectively. All clinically significant type III IM and
      dysplasia lesions were endoscopically detected. All nonvisible lesions were of
      types I and II with mild grade and no dysplasia. Ten patients were considered
      false positives and the lesions were associated with severe inflammation and
      antralization. CONCLUSION: The specific HD-WLE system showed satisfactory
      accuracy and high specificity during real-time, routine endoscopy practice.
      Specific mucosal patterns were correlated with level and grade of lesions. The
      sensitivity of the system is even higher when only clinically significant IM
      lesions are considered.

PMID- 24743506
TI  - Development of a chemically defined medium and discovery of new mitogenic growth
      factors for mouse hepatocytes: mitogenic effects of FGF1/2 and PDGF.
AB  - Chemically defined serum-free media for rat hepatocytes have been useful in
      identifying EGFR ligands and HGF/MET signaling as direct mitogenic factors for
      rat hepatocytes. The absence of such media for mouse hepatocytes has prevented
      screening for discovery of such mitogens for mouse hepatocytes. We present
      results obtained by designing such a chemically defined medium for mouse
      hepatocytes and demonstrate that in addition to EGFR ligands and HGF, the growth
      factors FGF1 and FGF2 are also important mitogenic factors for mouse hepatocytes.
      Smaller mitogenic response was also noticed for PDGF AB. Mouse hepatocytes are
      more likely to enter into spontaneous proliferation in primary culture due to
      activation of cell cycle pathways resulting from collagenase perfusion. These
      results demonstrate unanticipated fundamental differences in growth biology of
      hepatocytes between the two rodent species.

PMID- 24743507
TI  - A draft genome of the honey bee trypanosomatid parasite Crithidia mellificae.
AB  - Since 2006, honey bee colonies in North America and Europe have experienced
      increased annual mortality. These losses correlate with increased pathogen
      incidence and abundance, though no single etiologic agent has been identified.
      Crithidia mellificae is a unicellular eukaryotic honey bee parasite that has been
      associated with colony losses in the USA and Belgium. C. mellificae is a member
      of the family Trypanosomatidae, which primarily includes other insect-infecting
      species (e.g., the bumble bee pathogen Crithidia bombi), as well as species that
      infect both invertebrate and vertebrate hosts including human pathogens
      (e.g.,Trypanosoma cruzi, T. brucei, and Leishmania spp.). To better characterize
      C. mellificae, we sequenced the genome and transcriptome of strain SF, which was
      isolated and cultured in 2010. The 32 megabase draft genome, presented herein,
      shares a high degree of conservation with the related species Leishmania major.
      We estimate that C. mellificae encodes over 8,300 genes, the majority of which
      are orthologs of genes encoded by L. major and other Leishmania or Trypanosoma
      species. Genes unique to C. mellificae, including those of possible bacterial
      origin, were annotated based on function and include genes putatively involved in
      carbohydrate metabolism. This draft genome will facilitate additional
      investigations of the impact of C. mellificae infection on honey bee health and
      provide insight into the evolution of this unique family. 

PMID- 24743508
TI  - Dexmedetomidine reduces isoflurane-induced neuroapoptosis partly by preserving
      PI3K/Akt pathway in the hippocampus of neonatal rats.
AB  - Prolonged exposure to volatile anesthetics, such as isoflurane and sevoflurane,
      causes neurodegeneration in the developing animal brains. Recent studies showed
      that dexmedetomidine, a selective alpha2-adrenergic agonist, reduced isoflurane
      induced cognitive impairment and neuroapoptosis. However, the mechanisms for the
      effect are not completely clear. Thus, we investigated whether exposure to
      isoflurane or sevoflurane at an equivalent dose for anesthesia during brain
      development causes different degrees of neuroapoptosis and whether this
      neuroapoptosis is reduced by dexmedetomidine via effects on PI3K/Akt pathway that
      can regulate cell survival. Seven-day-old (P7) neonatal Sprague-Dawley rats were
      randomly exposed to 0.75% isoflurane, 1.2% sevoflurane or air for 6 h. Activated
      caspase-3 was detected by immunohistochemistry and Western blotting. Phospho-Akt,
      phospho-Bad, Akt, Bad and Bcl-xL proteins were detected by Western blotting in
      the hippocampus at the end of exposure. Also, P7 rats were pretreated with
      various concentrations of dexmedetomidine alone or together with PI3K inhibitor
      LY294002, and then exposed to 0.75% isoflurane. Terminal deoxyribonucleotide
      transferase-mediated dUTP nick end labeling (TUNEL) and activated caspase-3 were
      used to detect neuronal apoptosis in their hippocampus. Isoflurane, not
      sevoflurane at the equivalent dose, induced significant neuroapoptosis, decreased
      the levels of phospho-Akt and phospho-Bad proteins, increased the expression of
      Bad protein and reduced the ratio of Bcl-xL/Bad in the hippocampus.
      Dexmedetomidine pretreatment dose-dependently inhibited isoflurane-induced
      neuroapoptosis and restored protein expression of phospho-Akt and Bad as well as
      the Bcl-xL/Bad ratio induced by isoflurane. Pretreatment with single dose of 75
      ug/kg dexmedetomidine provided a protective effect similar to that with three
      doses of 25 ug/kg dexmedetomidine. Moreover, LY294002, partly inhibited
      neuroprotection of dexmedetomidine. Our results suggest that dexmedetomidine
      pretreatment provides neuroprotection against isoflurane-induced neuroapoptosis
      in the hippocampus of neonatal rats by preserving PI3K/Akt pathway activity. 

PMID- 24743509
TI  - Understanding the low photosynthetic rates of sun and shade coffee leaves:
      bridging the gap on the relative roles of hydraulic, diffusive and biochemical
      constraints to photosynthesis.
AB  - It has long been held that the low photosynthetic rates (A) of coffee leaves are
      largely associated with diffusive constraints to photosynthesis. However, the
      relative limitations of the stomata and mesophyll to the overall diffusional
      constraints to photosynthesis, as well as the coordination of leaf hydraulics
      with photosynthetic limitations, remain to be fully elucidated in coffee. Whether
      the low actual A under ambient CO2 concentrations is associated with the kinetic
      properties of Rubisco and high (photo)respiration rates also remains elusive.
      Here, we provide a holistic analysis to understand the causes associated with low
      A by measuring a variety of key anatomical/hydraulic and photosynthetic traits in
      sun- and shade-grown coffee plants. We demonstrate that leaf hydraulic
      architecture imposes a major constraint on the maximisation of the photosynthetic
      gas exchange of coffee leaves. Regardless of the light treatments, A was mainly
      limited by stomatal factors followed by similar limitations associated with the
      mesophyll and biochemical constraints. No evidence of an inefficient Rubisco was
      found; rather, we propose that coffee Rubisco is well tuned for operating at low
      chloroplastic CO2 concentrations. Finally, we contend that large diffusive
      resistance should lead to large CO2 drawdown from the intercellular airspaces to
      the sites of carboxylation, thus favouring the occurrence of relatively high
      photorespiration rates, which ultimately leads to further limitations to A.

PMID- 24743510
TI  - Uncoupling of glomerular IgA deposition and disease progression in alymphoplasia
      mice with IgA nephropathy.
AB  - Previous clinical and experimental studies have indicated that cells responsible
      for IgA nephropathy (IgAN), at least in part, are localized in bone marrow (BM).
      Indeed, we have demonstrated that murine IgAN can be experimentally reconstituted
      by bone marrow transplantation (BMT) from IgAN prone mice in not only normal
      mice, but also in alymphoplasia mice (aly/aly) independent of IgA+ cells homing
      to mucosa or secondary lymphoid tissues. The objective of the present study was
      to further assess whether secondary lymph nodes (LN) contribute to the
      progression of this disease. BM cells from the several lines of IgAN prone mice
      were transplanted into aly/aly and wild-type mice (B6). Although the transplanted
      aly/aly showed the same degree of mesangial IgA and IgG deposition and the same
      serum elevation levels of IgA and IgA-IgG immune-complexes (IC) as B6, even in
      extent, the progression of glomerular injury was observed only in B6. This
      uncoupling in aly/aly was associated with a lack of CD4+ T cells and macrophage
      infiltration, although phlogogenic capacity to nephritogenic IC of renal resident
      cells was identical between both recipients. It is suggested that secondary LN
      may be required for the full progression of IgAN after nephritogenic IgA and
      IgA/IgG IC deposition.

PMID- 24743511
TI  - Endothelial cell-derived fibronectin extra domain A promotes colorectal cancer
      metastasis via inducing epithelial-mesenchymal transition.
AB  - Recent evidence has been suggesting the important roles of endothelial cells
      (ECs) involved in the pathogenesis of several cancers, including colorectal
      carcinomas (CRCs), but the underlying mechanism remains elusive. We have
      demonstrated previously that CRC-derived fibronectin extra domain A (EDA)
      promotes vasculogenesis, tumorigenesis and metastasis of CRCs. At the current
      study, we showed that EC-secreted EDA promotes the metastatic capacity CRC cells
      via inducing an epithelial-mesenchymal transition. In vitro and in vivo
      experiments showed that EC-secreted EDA, via the interaction with integrin
      alpha9beta1 on neighboring CRC cells, leads to the activation of focal adhesion
      kinase as well as Rac signalings, thus strengthens the polarity of cytoskeleton
      and promotes the invasion capacity of CRC cells. Furthermore, Erk signaling
      pathway was revealed to critically mediate the effect of EC-derived EDA on CRC
      cells. Our findings reveal a novel oncogenic role of ECs in promoting CRC
      malignancy through secreting EDA.

PMID- 24743512
TI  - Expression and role of the embryonic protein SOX2 in head and neck squamous cell
      carcinoma.
AB  - Recently, SOX2 has been identified as a potential lineage-specific oncogene in
      lung squamous cell carcinomas. Since head and neck squamous cell carcinomas
      (HNSCC) are morphologically and clinically highly related to lung squamous cell
      carcinomas, we hypothesized that SOX2 also plays an oncogenic role in this tumor
      entity. We assembled a cohort of 496 patients with HNSCC, including 253
      metastases and 135 recurrences. SOX2 amplification (FISH) and SOX2 protein
      expression (immunohistochemistry) were correlated with molecular and
      clinicopathological parameters. In order to investigate the functional role of
      SOX2 in human HNSCC, SOX2 knockdown and overexpression in SCC-25 cells were
      generated by lentiviral constructs and subjected to cell cycle analysis,
      proliferation and apoptosis assays. Furthermore, SOX2 expression was correlated
      with the expression of proliferation and apoptosis-related proteins in primary
      HNSCC samples. SOX2 amplification was detected in 21% of primary HNSCC and mostly
      observed in a concordant manner between primary tumors and corresponding
      metastatic tissues. Overall, SOX2 amplification resulted in protein
      overexpression and was mutually exclusive with human papillomavirus infection.
      SOX2 protein overexpression was associated with clinicopathological parameters of
      worse outcome. Functionally, SOX2 induced the expression of the antiapoptotic
      protein BCL-2 and enhanced resistance to apoptosis-inducing agents including
      cisplatin, indicating SOX2 as a mediator of therapy resistance in human HNSCC.
      Targeting SOX2 and related molecular downstream pathways such as BCL-2 may
      enhance therapy efficacy in SOX2-expressing HNSCC.

PMID- 24743513
TI  - Attenuation of natural killer cell functions by capsaicin through a direct and
      TRPV1-independent mechanism.
AB  - The assessment of the biological activity of capsaicin, the compound responsible
      for the spicy flavor of chili pepper, produced controversial results, showing
      either carcinogenicity or cancer prevention. The innate immune system plays a
      pivotal role in cancer pathology and prevention; yet, the effect of capsaicin on
      natural killer (NK) cells, which function in cancer surveillance, is unclear.
      This study found that capsaicin inhibited NK cell-mediated cytotoxicity and
      cytokine production (interferon-gamma and tumor necrosis factor-alpha). Capsaicin
      impaired the cytotoxicity of NK cells, thereby inhibiting lysis of standard
      target cells and gastric cancer cells by modulating calcium mobilization in NK
      cells. Capsaicin also induced apoptosis in gastric cancer cells, but that effect
      required higher concentrations and longer exposure times than those required to
      trigger NK cell dysfunction. Furthermore, capsaicin inhibited the cytotoxicity of
      isolated NK cells and of an NK cell line, suggesting a direct effect on NK cells.
      Antagonists of transient receptor potential vanilloid subfamily member 1 (TRPV1),
      a cognate capsaicin receptor, or deficiency in TRPV1 expression failed to prevent
      the defects induced by capsaicin in NK cells expressing functional TRPV1. Thus,
      the mechanism of action of capsaicin on NK cells is largely independent of TRPV1.
      Taken together, capsaicin may have chemotherapeutic potential but may impair NK
      cell function, which plays a central role in tumor surveillance.

PMID- 24743514
TI  - Bioactivation of the human carcinogen aristolochic acid.
AB  - Aristolochic acids are potent human carcinogens; the role of phase II metabolism
      in their bioactivation is unclear. Accordingly, we tested the ability of the
      partially reduced metabolites, N-hydroxyaristolactams (AL-NOHs), and their N-O
      sulfonated and N-O-acetylated derivatives to react with DNA to form aristolactam
      DNA adducts. AL-NOHs displayed little or no activity in this regard while the
      sulfo- and acetyl compounds readily form DNA adducts, as detected by (32)P-post
      labeling analysis. Mouse hepatic and renal cytosols stimulated binding of AL-NOHs
      to DNA in the presence of adenosine 3'-phosphate 5'-phosphosulfate (PAPS) but not
      of acetyl-CoA. Using Time of Flight liquid chromatography/mass spectrometry, N
      hydroxyaristolactam I formed the sulfated compound in the presence of PAPS and
      certain human sulfotransferases, SULT1B1 >>> SULT1A2 > SULT1A1 >>> SULT1A3. The
      same pattern of SULT reactivity was observed when N-hydroxyaristolactam I was
      incubated with these enzymes and PAPS and the reaction was monitored by formation
      of aristolactam-DNA adducts. In the presence of human NAD(P)H: quinone
      oxidoreductase, the ability of aristolochic acid I to bind DNA covalently was
      increased significantly by addition of PAPS and SULT1B1. We conclude from these
      studies that AL-NOHs, formed following partial nitroreduction of aristolochic
      acids, serve as substrates for SULT1B1, producing N-sulfated esters, which, in
      turn, are converted to highly active species that react with DNA and,
      potentially, cellular proteins, resulting in the genotoxicity and nephrotoxicity
      associated with ingestion of aristolochic acids by humans.

PMID- 24743515
TI  - Increased leukocyte mitochondrial DNA copy number is associated with oral
      premalignant lesions: an epidemiology study.
AB  - Although changes in the mitochondrial DNA (mtDNA) copy number in peripheral blood
      leukocytes (PBLs) have been linked to increased susceptibility to several
      cancers, the relationship between the mtDNA copy number in PBLs and the risk of
      cancer precursors has not been investigated. In this study, we measured the
      relative mtDNA copy number in PBLs of 143 patients with histologically confirmed
      oral premalignant lesions (OPLs) and of 357 healthy controls that were frequency
      matched to patients according to age, sex and race. OPL patients had a
      significantly higher mtDNA copy number than the controls (1.36 +/- 0.74 versus
      1.11 +/- 0.32; P < 0.001). In analyses stratified by sex, race, alcohol
      consumption and smoking status, the mtDNA copy number was higher in the OPL
      patients than in the controls in all the strata. Using the median mtDNA copy
      number in the control group as a cutoff, we found that individuals with a high
      mtDNA copy number had significantly higher risk of having OPLs than individuals
      with a low mtDNA copy number (adjusted odds ratio, 1.93; 95% confidence interval,
      1.23-3.05, P = 0.004). Analysis of the joint effect of alcohol consumption and
      smoking revealed even greater risk for OPLs. Our results suggest that high mtDNA
      copy number in PBLs is significantly associated with having OPLs. To our
      knowledge, this is the first epidemiologic study to show that the mtDNA copy
      number may indicate the risk of cancer precursors.

PMID- 24743517
TI  - Systematic investigation of contribution of genetic variation in the HLA-DP
      region to cervical cancer susceptibility.
AB  - Compared with the other human leukocyte antigen (HLA) genes, few studies have
      evaluated the role of HLA-DP genes in cervical cancer pathogenesis. A recent
      genome-wide association study (GWAS) in the Swedish population has identified a
      susceptibility locus for cervical cancer within the HLA-DP region. To further
      study this locus, we imputed classic HLA alleles using single-nucleotide
      polymorphism (SNP) data and analysed 449 genotyped and 3066 imputed SNPs in 1034
      cervical cancer patients and 3948 controls. We confirmed that the strongest
      signal came from a SNP located at HLA-DPB2 [rs3117027, odds ratio (OR) = 1.29,
      95% confidence interval (CI) = 1.16-1.43, P = 1.9 * 10(-6) for A allele] and that
      this effect is not driven by associations with classic HLA alleles. In silico
      analysis further revealed that this SNP is highly correlated with rs3129294 (D' =
      1, r(2) = 0.95 in controls), which may have a putative regulatory function. We
      also identified an independent association at DPB1*0402, which conferred
      decreased risk of cervical cancer (OR = 0.75, 95% CI = 0.63-0.89, P = 7.0 * 10(
      4)) and is independent of previously described associations with HLA-B*0702,
      DRB1*1501-DQB1*0602, and DRB1*1301-DQA1*0103-DQB1*0603. No association was found
      with the two SNPs (rs4282438 or rs9277952) that were recently identified within
      the HLA-DP region in a cervical cancer GWAS in the Chinese population. Our study
      provides the first systematic investigation of the association of genetic
      variants in the HLA-DP region with cervical cancer susceptibility and provides
      further insight into the contribution of polymorphisms in the HLA-DP region to
      risk of cervical cancer.

PMID- 24743516
TI  - The complex landscape of pancreatic cancer metabolism.
AB  - Pancreatic ductal adenocarcinomas (PDA) are extremely aggressive cancers and
      currently available therapies are only minimally effective in treating this
      disease. Tackling this devastating cancer has been a major challenge to the
      scientific and medical communities, in part due to its intense therapeutic
      resistance. One of the aspects of this tumor that contributes to its aggressive
      behavior is its altered cellular metabolism. Indeed, PDA cells seem to possess
      the ability to adapt their metabolism to the particular environment to which they
      are exposed, including utilizing diverse fuel sources depending on their
      availability. Moreover, PDA tumors are efficient at recycling various metabolic
      substrates through activation of different salvage pathways such as autophagy and
      macropinocytosis. Together, these diverse metabolic adaptations allow PDA cells
      to survive and thrive in harsh environments that may lack nutrients and oxygen.
      Not surprisingly, given its central role in the pathogenesis of this tumor,
      oncogenic Kras plays a critical role in much of the metabolic reprogramming seen
      in PDA. In this review, we discuss the metabolic landscape of PDA tumors,
      including the molecular underpinnings of the key regulatory nodes, and describe
      how such pathways can be exploited for future diagnostic and therapeutic
      approaches.

PMID- 24743518
TI  - Three groups of transposable elements with contrasting copy number dynamics and
      host responses in the maize (Zea mays ssp. mays) genome.
AB  - Most angiosperm nuclear DNA is repetitive and derived from silenced transposable
      elements (TEs). TE silencing requires substantial resources from the plant host,
      including the production of small interfering RNAs (siRNAs). Thus, the
      interaction between TEs and siRNAs is a critical aspect of both the function and
      the evolution of plant genomes. Yet the co-evolutionary dynamics between these
      two entities remain poorly characterized. Here we studied the organization of TEs
      within the maize (Zea mays ssp mays) genome, documenting that TEs fall within
      three groups based on the class and copy numbers. These groups included DNA
      elements, low copy RNA elements and higher copy RNA elements. The three groups
      varied statistically in characteristics that included length, location, age,
      siRNA expression and 24:22 nucleotide (nt) siRNA targeting ratios. In addition,
      the low copy retroelements encompassed a set of TEs that had previously been
      shown to decrease expression within a 24 nt siRNA biogenesis mutant (mop1). To
      investigate the evolutionary dynamics of the three groups, we estimated their
      abundance in two landraces, one with a genome similar in size to that of the
      maize reference and the other with a 30% larger genome. For all three accessions,
      we assessed TE abundance as well as 22 nt and 24 nt siRNA content within leaves.
      The high copy number retroelements are under targeted similarly by siRNAs among
      accessions, appear to be born of a rapid bust of activity, and may be currently
      transpositionally dead or limited. In contrast, the lower copy number group of
      retrolements are targeted more dynamically and have had a long and ongoing
      history of transposition in the maize genome.

PMID- 24743519
TI  - Rates of febrile neutropenia with pegfilgrastim on same day versus next day of
      CHOP with or without rituximab.
AB  - Febrile neutropenia is a complication of myleotoxic chemotherapy that can
      markedly decrease quality of life and increase healthcare costs. A granulocyte
      colony stimulating factor (G-CSF) is used to increase neutrophil production to
      reduce the risk of developing febrile neutropenia. However, G-CSF administered on
      the same day as chemotherapy can worsen and prolong neutropenia. To study and
      compare the effects of pegfilgrastim on the incidence of febrile neutropenia and
      grade 4 neutropenia in patients receiving pegfilgrastim on the same day (day 1)
      versus the next day (day 2 or beyond) of chemotherapy, a retrospective, single
      center, nonrandomized, cohort study was carried out of adult non-Hodgkin's
      lymphoma patients who received pegfilgrastim 6 mg subcutaneously on day 1 or
      beyond of CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) with or
      without rituximab every 3 weeks. Six hundred and fifty-five chemotherapy cycles
      (320 cycles for the same day and 335 cycles for the next day) were evaluable in
      141 patients. Among all cycles, the incidence of febrile neutropenia was 9.4
      versus 5.1% in the same-day versus the next-day group (P=0.03). The incidence of
      febrile neutropenia was the highest after the first cycle in the same-day group,
      which was 19.4, versus 11.1% for the next-day group (P=0.27). There were three
      deaths among patients who developed febrile neutropenia, including two in the
      next-day group versus one in the same-day group. In conclusion, our findings
      support the need for a randomized phase III study to fully evaluate whether a G
      CSF is safer when administered on the next day versus the same day of
      chemotherapy. 

PMID- 24743520
TI  - Induction of aldo-keto reductases (AKR1C1 and AKR1C3) abolishes the efficacy of
      daunorubicin chemotherapy for leukemic U937 cells.
AB  - Continuous exposure to daunorubicin (DNR) confers resistance against the drug
      elicited lethality of leukemic cells and then reduces the remission rate.
      However, the detailed mechanisms involved in resistance development of leukemic
      cells to DNR remain unclear. Upregulation of aldo-keto reductases (AKRs) in human
      leukemic U937 cells was evaluated by gene-specific PCR and western blot analyses,
      and the contribution of AKRs toward the DNR sensitivity was assessed using gene
      expression and RNA-interference techniques and specific inhibitors. In addition,
      DNR reduction and cell differentiation were analyzed by fluorescence high
      performance liquid chromatography and flow cytometry, respectively. Treatment
      with high doses of DNR triggered apoptotic induction of U937 cells through the
      production of reactive oxygen species (ROS) and a ROS-dependent mechanism. In
      contrast, DNR, at its sublethal doses, induced the expression of AKR1C1 and
      AKR1C3, both of which reduced the DNR sensitivity of the cells. The enzymes did
      not interfere with the cell differentiation caused by DNR, whereas their
      upregulation facilitated reduction of the anticancer drug and a ROS-derived lipid
      aldehyde 4-hydroxy-2-nonenal. These results suggest crucial roles of AKR1C1 and
      AKR1C3 in the acquisition of DNR resistance of leukemic cells by metabolizing
      both DNR and cytotoxic aldehydes derived from ROS-linked lipid peroxidation. 

PMID- 24743522
TI  - First performance tests of a digital photon counter (DPC) array coupled to a
      CsI(Tl) crystal matrix for potential use in SPECT.
AB  - The digital photon counter (DPC) is a recently developed type of digital silicon
      photomultiplier that combines low dark count rates, low readout noise, and fully
      digital, integrated readout circuitry with neighbor logic capability, system
      scalability, and MR compatibility. These are desirable properties for application
      in scintillation detectors for single photon emission computed tomography
      (SPECT). In this work, the feasibility of using a DPC array in combination with a
      CsI(Tl) crystal matrix as a potential detector for SPECT is investigated for the
      first time. Given the relatively long decay time of CsI(Tl), an important
      consideration is the influence on the detector performance of the DPC dark count
      rate as a function of temperature. We present a preliminary characterization of a
      detector assembled with an array of 2 * 2 * 3 mm(3) CsI(Tl) crystals. Preparatory
      measurements were acquired with a (57)Co source in order to optimize the light
      guide thickness and the sensor settings. The spatial resolution of the detector
      was tested by acquiring flood maps with (57)Co as well as (99m)Tc sources. Three
      crystal identification algorithms were compared for the reconstruction of the
      flood maps. All crystal elements could be visualized clearly and high values of
      peak-to-valley ratios were achieved. Energy resolutions of ~18.5% FWHM and ~15%
      FWHM were measured at 122 keV and 140 keV, respectively. Temperature-dependent
      measurements indicate that the detector can work satisfactorily up to about 15 
      degrees C. 

PMID- 24743523
TI  - Prediction of large-for-gestation neonates with first-trimester maternal serum
      PAPP-A.
AB  - AIM: The aim of this paper was to identify maternal/pregnancy characteristics,
      first trimester ultrasound parameters and biochemical indices which are
      significant independent predictors of large-for-gestational age (LGA) neonates.
      METHODS: An Observational cross-sectional study was conducted at the Fetal
      Medicine Unit, Department of Obstetrics and Gynecology of the University of Udine
      (Italy). Seventy-two singleton pregnancies presenting for screening for
      chromosomal abnormalities by nuchal translucency and maternal serum biochemistry
      at 11-14 weeks. Linear regression was applied to develop first trimester
      prediction models for LGA. RESULTS: Maternal height, parity, smoking, assisted
      conception and pregnancy-associated plasma protein-A were significant independent
      predictors of LGA. PAPP-A cut-off value expressed in MoM of 1.25 used for the
      study was chosen to obtain good sensitivity and specificity values. CONCLUSION:
      Prediction for birthweight deviations (LGA) is feasible using data available at
      the routine 11-14 weeks' examination.

PMID- 24743521
TI  - Distribution and clinical manifestations of Cryptosporidium species and subtypes
      in HIV/AIDS patients in Ethiopia.
AB  - BACKGROUND: Cryptosporidiosis is an important cause for chronic diarrhea and
      death in HIV/AIDS patients. Among common Cryptosporidium species in humans, C.
      parvum is responsible for most zoonotic infections in industrialized nations.
      Nevertheless, the clinical significance of C. parvum and role of zoonotic
      transmission in cryptosporidiosis epidemiology in developing countries remain
      unclear. METHODOLOGY/PRINCIPAL FINDINGS: In this cross-sectional study, 520
      HIV/AIDS patients were examined for Cryptosporidium presence in stool samples
      using genotyping and subtyping techniques. Altogether, 140 (26.9%) patients were
      positive for Cryptosporidium spp. by PCR-RFLP analysis of the small subunit rRNA
      gene, belonging to C. parvum (92 patients), C. hominis (25 patients), C. viatorum
      (10 patients), C. felis (5 patients), C. meleagridis (3 patients), C. canis (2
      patients), C. xiaoi (2 patients), and mixture of C. parvum and C. hominis (1
      patient). Sequence analyses of the 60 kDa glycoprotein gene revealed a high
      genetic diversity within the 82 C. parvum and 19 C. hominis specimens subtyped,
      including C. parvum zoonotic subtype families IIa (71) and IId (5) and
      anthroponotic subtype families IIc (2), IIb (1), IIe (1) and If-like (2), and C.
      hominis subtype families Id (13), Ie (5), and Ib (1). Overall, Cryptosporidium
      infection was associated with the occurrence of diarrhea and vomiting. Diarrhea
      was attributable mostly to C. parvum subtype family IIa and C. hominis, whereas
      vomiting was largely attributable to C. hominis and rare Cryptosporidium species.
      Calf contact was identified as a significant risk factor for infection with
      Cryptosporidium spp., especially C. parvum subtype family IIa.
      CONCLUSIONS/SIGNIFICANCE: Results of the study indicate that C. parvum is a major
      cause of cryptosporidiosis in HIV-positive patients and zoonotic transmission is
      important in cryptosporidiosis epidemiology in Ethiopia. In addition, they
      confirm that different Cryptosporidium species and subtypes are linked to
      different clinical manifestations.

PMID- 24743524
TI  - ISMB 2014--the premier conference for the World's Computational Biologists.

PMID- 24743525
TI  - [Treatment strategy for patients with simultaneous cardiac and malignant
      diseases].
AB  - The choice of treatment strategy for patients with simultaneous cardiac and
      malignant diseases is often debatable. We report 11 patients with simultaneous
      cardiac and malignant diseases who were hospitalized in our institution over the
      past 6 years. The patients were 9 males and 2 females with a mean age of 71.9+/
      9.0 years old. There were 7 cases of ischemic heart disease( IHD), and 4 cases of
      valvular disease. Malignant diseases consisted of 4 cases of colon cancer, 2
      cases of pulmonary cancer, 2 cases of hepatic cancer, and 1 case each of sigmoid
      colon cancer with liver metastasis, gallbladder cancer, and pancreatic cancer.
      Eight of the 11 cases(73%)were hospitalized because of a symptom associated with
      cardiac disease, and malignant disease was diagnosed incidentally during
      examination or treatment. Four of the IHD cases preceded coronary
      revascularization by off-pump coronary artery bypass grafting (OPCAB) or
      percutaneous coronary intervention (PCI). Two of the valvular cases and 2 of the
      IHD cases underwent cardiac surgery after treatment of malignant diseases. In 3
      cases, only 1 of the diseases was treated. Seven cases died of malignant diseases
      at the present. The choice of treatment strategy should be established for
      patients with simultaneous cardiac and malignant diseases in consideration of the
      severity of the cardiac disease and the expected prognosis of the malignant
      disease because there is no standardized method of treatment. 

PMID- 24743526
TI  - [Clinical effects of tolvaptan for patients with stage 4-5 chronic kidney disease
      in cardiac surgery].
AB  - We report clinical effects of tolvaptan, a vasopressin V2 receptor antagonist, in
      cardiac surgery. Tolvaptan was administrated to 5 patients with non-dialysis
      dependent stage 4-5 chronic kidney disease (CKD) during an early postoperative
      stage. Tolvaptan increased urine output and improved respiratory function in all
      patients without causing hemodynamic deterioration. All patients were able to
      avoid initiating long-term hemodialysis during hospital stay. Tolvaptan was
      effective and safe after cardiac surgery for patients with severe CKD. 

PMID- 24743527
TI  - [Aortic and mitral valve replacement via right thoracotomy in the case of a
      patient with severe heart failure following right pneumonectomy].
AB  - We report a case of aortic valve replacement (AVR) and mitral valve replacement
      (MVR) in a patient with severe left ventricular dysfunction who had undergone
      right pneumonectomy for lung cancer 14 years previously. A 64-year-old man had
      cathecolamine-dependent heart failure due to bicuspid aortic valve stenosis,
      functional mitral valve regurgitation and impaired left ventricular function
      (left ventricular ejection fraction 13%)because of dilated cardiomyopathy. AVR
      and MVR were performed using St. Jude Medical mechanical valves with right
      thoracotomy because the heart had shifted to the right side. Poor left
      ventricular function and postoperative atrial fibrillation made it difficult to
      control low-output syndrome, but prolonged use of intra-aortic balloon pumping
      improved it gradually. Intraaortic balloon pumping( IABP) was removed 34 days
      after the operation, the respirator was removed with tracheotomy 63 days
      postoperatively, and the patient was discharged on the 177th postoperative day.
      Careful preoperative assessment and perioperative control of heart failure are
      important components of successful clinical management.

PMID- 24743528
TI  - [Resected thymic hyperplasia with myasthenia gravis and Lambert-Eaton myasthenic
      syndrome].
AB  - A 61-year-old male who noticed muscular weakness of his extremities, diplopia and
      slur his words was found to have a thymic tumor on computed tomography. The
      immunological examination showed incremental of anti Acetylcholine receptor
      antibody titer and anti P/Q-type voltage-gated calcium channels antibody titer.
      Electromyography showed decremental response to low frequency stimulations, and
      incremental response to high frequency stimulations. So he was diagnosed with
      thymic tumor combined with myasthenia gravis and Lambert-Eaton myasthenic
      syndrome. He treated with extended thymomectomy resulting in the improvement of
      his neurological symptoms. Five years after operation, the patient is well
      without any malignant diseases.

PMID- 24743529
TI  - [Adenocarcinoma and basaloid squamous cell carcinoma in the same lung lobe].
AB  - We encountered a rare case of an adenocarcinoma and basaloid squamous cell
      carcinoma in the same lung lobe. The patient was a 66-year-old female. During the
      observation of the course of angina pectoris, chest computed tomography( CT)
      showed a nodular shadow in the right upper lung field and a club like lesion
      dorsal to this shadow. Since the former lesion was diagnosed as an
      adenocarcinoma, right upper lobectomy and lymph node dissection were performed.
      The latter lesion was diagnosed as a basaloid squamous cell carcinoma by
      pathology. Basaloid squamous cell carcinoma is a relatively rare tumor associated
      with a poor prognosis that is classified as a subtype of squamous cell carcinoma.
      There have been no reported cases of this tumor developing concurrently with
      adenocarcinoma. Since there were no histological transition images, and
      immunostaining findings completely differed between the 2 tumors, these tumors
      may have incidentally developed during the same period in the same lung lobe.

PMID- 24743530
TI  - [Effectiveness of perioperative administration of eltrombopag in a patient with
      idiopathic thrombocytopenic purpura undergoing cardiovascular surgery].
AB  - We report a case of chronic aortic dissection and angina pectoris with idiopathic
      thrombocytopenic purpura treated perioperatively with eltrombopag. A 72-year-old
      man was admitted to our hospital because of significant enlargement of an ulcer
      like projection in the thoracic aorta revealed by chest computed tomography after
      acute aortic dissection. Laboratory data showed thrombocytopenia with idiopathic
      thrombocytopenic purpura. Eltrombopag was administered 12.5 mg daily and
      increased by 12.5 mg every 2 weeks until 37.5 mg/day to control idiopathic
      thrombocytopenic purpura(ITP). After 7 weeks' eltrombopag therapy, thrombocyte
      increased, and the patient underwent total arch replacement. Nine months later,
      coronary angiography revealed progression of coronary artery stenosis at the left
      main trunk. The patient underwent off-pump coronary artery bypass grafting 10
      days after initiation of eltrombopag therapy. His postoperative course was
      uneventful. Eltrombopag was suggested to be effective in perioperative management
      in a patient with idiopathic thrombocytopenic purpura undergoing cardiovascular
      surgery. 

PMID- 24743531
TI  - [Completion bentall procedure after aortic valve replacement].
AB  - A 51-year-old man, who had undergone aortic valve replacement with a mechanical
      valve 30 years ago, was referred to our hospital due to acute type A aortic
      dissection. Pre- and intra-operative echocardiographic evaluation showed no
      evidence of valve dysfunction or paravalvular leak. Intraoperative inspection
      revealed a thin pannus covering the leaflet housing of the mechanical valve,
      which we easily removed. We performed aortic root replacement while leaving the
      valve in situ, and total aortic arch replacement using elephant trunk technique
      under hypothermic circulatory arrest. He was discharged from the hospital 31 days
      after operation and retains normal valve function. For patients with aneurysms
      and acute type A aortic dissection having aortic valve prosthesis that does not
      require replacement, the completion Bentall procedure is a more secure and safer
      repair than complete aortic root reconstruction. 

PMID- 24743532
TI  - [Valve replacement for tricuspid infective endocarditis presenting paradoxical
      cerebral embolism].
AB  - Tricuspid valve infective endocarditis( IE) accounts for 5 to 10% of all IE. We
      encountered a 50-year old man who suffered from tricuspid valve IE presenting
      paradoxical multiple cerebral embolism with intracranial hemorrhage. On 6th day
      from his admission, we performed valve replacement for intractable tricuspid
      infective endocarditis regardless of acute phase of intracranial hemorrhage. The
      patient had an uneventful postoperative course with no neurological symptoms.

PMID- 24743533
TI  - [Discrete type subaortic stenosis disclosed by hemolytic anemia after aortic and
      mitral valve replacement].
AB  - We report a case of discrete type subaortic stenosis disclosed by hemolytic
      anemia 7 years after aortic and mitral prosthetic valve replacement. A 53-year
      old female complained of general fatigue, dyspnea, macrohematuria and hemolysis.
      She had undergone aortic valve replacement for non-coronary cusp perforation 15
      years before, and mitral valve replacement and tricuspid annuloplasty 7 years
      before. Echocardiography showed mitral prosthetic valve regurgitation (III/IV
      degree) and symptomatic hemolysis might be caused by accelerated blood flow
      through the prosthetic valve. A mild aortic stenosis (peak flow verocity:3.73
      m/s) was also pointed out. The redo double valve replacement was performed.
      Intraoperative findings showed discrete type subaortic stenosis due to extensive
      pannus formation, but that the previously implanted prosthetic valves were
      intact. The blood flow biased by the interference of the subaortic stenosis might
      have obstructed closure of the mitral prosthetic valve and caused mitral
      regurgitation. Postoperatively, hemolysis and mitral regurgitation were
      diminished, and aortic stenosis was improved.

PMID- 24743534
TI  - [Successful surgical treatment for acute type a aortic dissection in a patient
      with late pregnancy].
AB  - We report a case of successful surgical treatment for acute type A aortic
      dissection in a patient in late pregnancy. The patient was a 42-year-old woman
      who was pregnant for the 1st time. She was taken to hospital with a sudden onset
      of chest pain at 30 weeks' gestation. She was diagnosed with acute type A aortic
      dissection with annuloaortic ectasia (AAE) and aortic regurgitation, and was
      transferred to our hospital for further treatment. Emergency cesarean section and
      hysterectomy were performed, followed by modified Bentall operation on the next
      day. The postoperative course was uneventful for both the mother and the infant.
      Considering the severity of acute type A aortic dissection with AAE, aortic
      repair might have been performed as soon as possible after cesarean section.

PMID- 24743535
TI  - [Ultra powered stapling system for general lung surgery].
AB  - OBJECTIVE: Stapling systems can significantly improve lung tissue approximation
      during open and video-assisted thoracic surgery. We here evaluated an iDrive
      Ultra powered stapling system for lung resection. MATERIALS AND METHODS: The
      iDrive Ultra powered stapling system( Covidien) is the powered version of the
      EndoGIA stapling system. It comprises hand-held control unit combined with a
      loading unit,which is a powered EndoGIA- cartridges, for use in open and
      minimally invasive thoracic surgery. The mounted control unit has uses as
      follows:controlling the accurate placement of the cartridge by orientating the
      tip of the rigid shaft;and controlling the closure of the stapler and the firing.
      From April to July 2013, the system was used for a consecutive series of 15
      patients during thoracic lung surgery. RESULTS: There were 6 women and 9 men,
      with a mean age of 62 years. The following procedures were performed:lobectomies,
      segmentectomies, and wedge resections. The system was used for stapling lung
      parenchyma for wedge resection(5 patients), segmentectomy( 2 patients), or
      fissure division (9 patients). There were no stapling failures and no
      complications related to use of the staplers. CONCLUSIONS: The new powered and
      handy stapling system is safe and efficient for lung resection.

PMID- 24743536
TI  - [Acute empyema with fistula successfully treated by curettage and endobronchial
      Watanabe spigot (EWS)].
AB  - A 49-year-old woman was referred to our hospital because of empyema. A chest
      drainage tube inserted and lavage performed. Her general condition improved but
      the infection and a major air leakage remained. On the 10th day after chest
      drainage, we performed thoracoscopic debridement and occlusion of bronchopleural
      fistulas using cellulose oxidized( Surgicel) and fibrin glue. Expansion of the
      lung and the improvement of inflammation were observed. but a major air leakage
      remained. On 29th postoperative day, we performed bronchial embolization using
      endobronchial Watanabe spigot (EWS). The leakage stopped the 7 days after
      bronchial embolization, we removed chest tube and 10 days after bronchial
      embolization she was discharged. 

PMID- 24743537
TI  - [Ascending aorta-abdominal aorta bypass for atypical coarctation with intractable
      hypertension due to aortitis syndrome; report of a case].
AB  - A 63-year-old woman was admitted to our hospital. Aortitis syndrome was diagnosed
      12 years ago. She developed intractable hypertension and a computed tomography
      scan showed coarctation of descending aorta with severe calcificaiton. Her ankle
      brachial pressure index (ABI) was 0.74 on the right side and was 0.70 on the left
      side. She underwent a bypass operation with 14 mm-diameter prosthetic graft from
      ascending aorta to the infrarenal abdominal aorta without using cardiopulmonary
      bypass. Postoperatively, ABI was 1.22 on the right side and was 1.21 on the left
      side, and hypertension was well controlled.

PMID- 24743538
TI  - [Aortic root replacement with a freestyle stentless valve for prosthetic valve
      detachment caused by aortitis syndrome; report of a case].
AB  - A surgical case of a 65-year-old man with aortitis syndrome is presented. The
      patient had undergone aortic valve replacement for aortic valve regurgitation
      with a mechanical prosthesis, followed by a re-do operation (valve fixation) for
      prosthetic valve detachment 6 months after the 1st operation. Three months after
      the 2nd operation, perivalvular leakage due to valve detachment was detected
      again. Aorticroot replacement with a Freestyle stentless valve( full root
      technique) was performed. Prednisolone was given postoperatively, and no valve
      detachment nor pseudoaneurysm formation has been noted for 8 years. 

PMID- 24743539
TI  - [Coronary artery spasm induced by neuroleptic malignant syndrome during off-pump
      coronary artery bypass grafting; report of a case].
AB  - A 61-year-old woman with a left main lesion and coronary spastic angina was
      scheduled for off-pump coronary artery bypass grafting (OPCAB). She had been
      orally receiving selective serotonin reuptake inhibitor( SSRI) for the treatment
      of depression. OPCAB to left anterior discending artery( LAD) and left circumflex
      branch (LCX) was performed using the bilateral internal thoracic arteries
      assisted by intra-aortic balloon pumping. When the sternotomy was going to be
      closed, ST elevation of electrocardiogram (ECG) occurred and was followed by
      complete atrio-ventricular (AV) block. After returning to intensive care unit
      (ICU), the patient showed rapid elevation of the body temperature, excessive
      sweating, progressive metabolic acidosis, and abnormal high levels in white blood
      cell count and creatine phosphokinase. On suspicion of neuroleptic malignant
      syndrome(NMS) onset, dantrolene sodium hydrate was administered, resulting in
      marked improvement of the symptoms. We have concluded that this case was an NMS
      combined with coronary artery spasm during OPCAB treated successfully with
      dantrolene sodium hydrate. 

PMID- 24743540
TI  - [Large cell neuroendocrine carcinoma of the thymus; report of a case].
AB  - A 55-year-old man presented with an anterior mediastinal tumor, which was
      detected on a computed tomography scan for close investigation of blood-stained
      sputum. Operation was performed with the clinical diagnosis of a thymic carcinoma
      and the tumor was resected completely. The pathological findings revealed Masaoka
      stage IV, large cell neuroendocrine carcinoma of the thymus. The patients
      received postoperative chemotherapy and is well without recurrence for 10 months
      after the surgery. 

PMID- 24743541
TI  - [Ectopic mediastinal parathyroid tumor resected by video-assisted thoracic
      surgery with intraoperative methylene blue infusion; report of a case].
AB  - We report a surgical case of ectopic mediastinal parathyroid tumor resected by
      video-assisted thoracic surgery with intraoperative methylene blue infusion. It
      is often difficult to detect ectopic mediastinal parathyroid tumor during the
      operation because the tumor is soft, small and buried under mediastinal tissue.
      After methylene blue 4 mg/kg intravenously administration, the tumor was
      gradually dyed blue and easily detected and resected by video-assisted thoracic
      surgery. It is useful of methylene blue for detection of ectopic mediastinal
      parathyroid tumor. 

PMID- 24743542
TI  - Differences in innate cytokine responses between European and African children.
AB  - Although differences in immunological responses between populations have been
      found in terms of vaccine efficacy, immune responses to infections and prevalence
      of chronic inflammatory diseases, the mechanisms responsible for these
      differences are not well understood. Therefore, innate cytokine responses
      mediated by various classes of pattern-recognition receptors including Toll-like
      receptors (TLR), C-type lectin receptors (CLRs) and nucleotide-binding
      oligomerisation domain-like receptors (NLRs) were compared between Dutch
      (European), semi-urban and rural Gabonese (African) children. Whole blood was
      stimulated for 24 hours and the pro-inflammatory tumor necrosis factor (TNF) and
      the anti-inflammatory/regulatory interleukin-10 (IL-10) cytokines in culture
      supernatant were measured by enzyme-linked immunosorbent assay (ELISA). Gabonese
      children had a lower pro-inflammatory response to poly(I:C) (TLR3 ligand), but a
      higher pro-inflammatory response to FSL-1 (TLR2/6 ligand), Pam3 (TLR2/1 ligand)
      and LPS (TLR4 ligand) compared to Dutch children. Anti-inflammatory responses to
      Pam3 were also higher in Gabonese children. Non-TLR ligands did not induce
      substantial cytokine production on their own. Interaction between various TLR and
      non-TLR receptors was further assessed, but no differences were found between the
      three populations. In conclusion, using a field applicable assay, significant
      differences were observed in cytokine responses between European and African
      children to TLR ligands, but not to non-TLR ligands. 

PMID- 24743543
TI  - Rs495828 polymorphism of the ABO gene is a predictor of enalapril-induced cough
      in Chinese patients with essential hypertension.
AB  - OBJECTIVE: ABO genetic polymorphisms have recently been associated with
      angiotensin-converting enzyme (ACE) activity and inflammation, which play a
      critical role in the pathogenic mechanism of ACE inhibitor-induced cough.
      Therefore, the current study determined the association of ABO genetic
      polymorphisms with enalapril-induced cough in Chinese patients with essential
      hypertension. METHODS: A total of 450 essential hypertensive patients treated
      with 10 mg of enalapril maleate were genotyped for ABO genetic polymorphisms
      using the PCR-direct sequencing method. Cough was recorded when patients were
      bothered by cough and respiratory symptoms during enalapril treatment without an
      identifiable cause. RESULTS: The distribution of rs8176740 and rs495828 was
      different between the coughers and the controls [P=0.039; odds ratio (OR)=0.70,
      P=0.018; OR=1.41]. The risk of enalapril-induced cough in the rs495828 TT
      carriers was increased (P=0.008; OR=2.69), which remained significant after false
      discovery rate correction. The results for the rs8176740 polymorphism were
      significant in the female subgroup (P=0.027; OR=0.22). Haplotype analysis of the
      four ABO polymorphisms (rs8176746/rs8176740/rs495828/rs12683493) showed that the
      frequency of the GATC haplotype was higher in the coughers than those in the
      controls (26.6 vs. 18.8%, P=0.033; OR=1.43). CONCLUSION: The rs495828
      polymorphism was associated with enalapril-induced cough and may serve as a
      useful pharmacogenomics marker of the safety of enalapril in Chinese patients
      with essential hypertension. The mechanism for the associations may involve the
      effects of the ABO gene or ABO blood type on ACE activity and inflammation.

PMID- 24743544
TI  - Genetic variants may play an important role in mRNA-miRNA interaction: evidence
      for haplotype-dependent downregulation of ABCC2 (MRP2) by miRNA-379.
AB  - BACKGROUND: The functional influence of single-nucleotide polymorphisms (SNPs) of
      the ATP-binding cassette (ABC) transporter ABCC2 (MRP2) has been characterized in
      numerous studies. The aim of this study was to address the question of whether
      distinct ABCC2 haplotypes, which differ in their mRNA secondary structures, show
      an influence on the degree of mRNA and protein downregulation through miRNA
      interaction. METHODS: A model using human peripheral blood monocytic cells
      (PBMCs) isolated from healthy Caucasian volunteers, with three defined ABCC2
      haplotypes comprising the 5'-UTR SNP -24C>T, the 1249G>A SNP (V417I), and the
      silent 3972C>T SNP, was outlined. Cells were transiently transfected with miRNA
      379, already known to target ABCC2 in HepG2 cells. RESULTS: ABCC2 was
      downregulated through miR-379 in a haplotype-dependent manner: the wild-type
      CGC/CGC was modestly affected (mRNA: -12.7+/-4.2%, protein: -9.9+/-0.1%), whereas
      variant haplotypes were more strongly suppressed: CGT/CGT (mRNA: -36.7+/-2.4%,
      protein: -21.6+/-0.4%) and TGT/TGT (mRNA: -55.7+/-1.2%, protein: -46.3+/-4.0%).
      In addition, glutathione-methylfluorescein efflux was significantly reduced in
      miR-379-transfected peripheral blood monocytic cells corresponding to ABCC2
      protein expression. CONCLUSION: This observation may suggest a differential
      suppression of ABCC2 by miR-379 caused by haplotype-dependent differences in mRNA
      secondary structures, resulting in changes in mRNA target accessibility or mRNA
      stability.

PMID- 24743545
TI  - Rat hepatocytes weighted gene co-expression network analysis identifies specific
      modules and hub genes related to liver regeneration after partial hepatectomy.
AB  - The recovery of liver mass is mainly mediated by proliferation of hepatocytes
      after 2/3 partial hepatectomy (PH) in rats. Studying the gene expression profiles
      of hepatocytes after 2/3 PH will be helpful to investigate the molecular
      mechanisms of liver regeneration (LR). We report here the first application of
      weighted gene co-expression network analysis (WGCNA) to analyze the biological
      implications of gene expression changes associated with LR. WGCNA identifies 12
      specific gene modules and some hub genes from hepatocytes genome-scale microarray
      data in rat LR. The results suggest that upregulated MCM5 may promote hepatocytes
      proliferation during LR; BCL3 may play an important role by activating or
      inhibiting NF-kB pathway; MAPK9 may play a permissible role in DNA replication by
      p38 MAPK inactivation in hepatocytes proliferation stage. Thus, WGCNA can provide
      novel insight into understanding the molecular mechanisms of LR. 

PMID- 24743546
TI  - From Clinical Misdiagnosis to Electrophysiological Diagnosis: Two Male Asystole
      Cases.
AB  - Differential diagnosis of epilepsy and syncope may be difficult. Arrhythmias such
      as asystole, or ventricular fibrillation, may lead to cerebral hypoperfusion
      mimicking partial or secondary generalized tonic-clonic seizures. While
      performing an electroencephalogram (EEG) for epilepsy diagnosis, simultaneous
      electrocardiogram (ECG) recording may detect cardiac pathology. In this article,
      through 2 cases, who had cardiac asystole during the EEG, we demonstrate the
      importance of ECG during EEG. To rule out cardiac pathology in syncope cases, all
      necessary investigations must be done. 

PMID- 24743547
TI  - Spatial and Temporal EEG-fMRI Changes During Preictal and Postictal Phases in a
      Patient With Posttraumatic Epilepsy.
AB  - The combined use of electroencephalography (EEG) and functional magnetic
      resonance imaging (EEG-fMRI) in epilepsy allows the noninvasive hemodynamic
      characterization of epileptic discharge-related neuronal activations. The aim of
      this study was to investigate pathophysiologic mechanisms underlying epileptic
      activity by exploring the spatial and temporal distribution of fMRI signal
      modifications during seizure in a single patient with posttraumatic epilepsy. EEG
      and fMRI data were acquired during two scanning sessions: a spontaneous critical
      episode was observed during the first, and interictal events were recorded during
      the second. The EEG-fMRI data were analyzed using the general linear model (GLM).
      Blood oxygenation level-dependent (BOLD) localization derived from the preictal
      and artifact-free postictal phase was concordant with the BOLD localization of
      the interictal epileptiform discharges identified in the second session, pointing
      to a left perilesional mesiofrontal area. Of note, BOLD signal modifications were
      already visible several seconds before seizure onset. In brief, BOLD activations
      from the preictal, postictal, and interictal epileptiform discharge analysis
      appear to be concordant with the clinically driven localization hypothesis,
      whereas a widespread network of activations is detected during the ictal phase in
      a partial seizure. 

PMID- 24743548
TI  - An improved systematic approach to predicting transcription factor target genes
      using support vector machine.
AB  - Biological prediction of transcription factor binding sites and their
      corresponding transcription factor target genes (TFTGs) makes great contribution
      to understanding the gene regulatory networks. However, these approaches are
      based on laborious and time-consuming biological experiments. Numerous
      computational approaches have shown great potential to circumvent laborious
      biological methods. However, the majority of these algorithms provide limited
      performances and fail to consider the structural property of the datasets. We
      proposed a refined systematic computational approach for predicting TFTGs. Based
      on previous work done on identifying auxin response factor target genes from
      Arabidopsis thaliana co-expression data, we adopted a novel reverse-complementary
      distance-sensitive n-gram profile algorithm. This algorithm converts each
      upstream sub-sequence into a high-dimensional vector data point and transforms
      the prediction task into a classification problem using support vector machine
      based classifier. Our approach showed significant improvement compared to other
      computational methods based on the area under curve value of the receiver
      operating characteristic curve using 10-fold cross validation. In addition, in
      the light of the highly skewed structure of the dataset, we also evaluated other
      metrics and their associated curves, such as precision-recall curves and cost
      curves, which provided highly satisfactory results. 

PMID- 24743549
TI  - Inter-hospital transfer of ECMO-assisted patients with a portable miniaturized
      ECMO device: 4 years of experience.
AB  - OBJECTIVES: Extracorporeal membrane oxygenation (ECMO) in patients with severe
      pulmonary failure is able to keep patients alive until organ regeneration, until
      shunting out for further diagnostic and therapeutic options or until
      transportation to specialized centers. Nonetheless, extracorporeal techniques
      require a high degree of expertise, so that a confinement to specialized centers
      is meaningful. Following from this requirement, the need for inter-hospital
      transfer of patients with severely compromised pulmonary function is rising.
      METHODS: We report about our experience with a portable ECMO system during inter
      hospital air or ground transfer of patients with cardiopulmonary failure.
      RESULTS: The portable ECMO system was used for transportation to the center and
      in-hospital treatment in 36 patients with an average age of 53 years suffering
      from respiratory failure. Accordingly, the ECMO system was implanted as a veno
      venous extracorporeal system. Pre-ECMO ventilation time was 5.2 (2-9) days.
      Twelve patients were transported to our institution by ground and 24 patients by
      air ambulance over a median distance of 46 km. With the assistance of the ECMO
      device, prompt stabilization of cardiopulmonary function could be achieved in all
      patients without any technical complications. Post-ECMO ventilation was 9.8 days.
      Weaning from the ECMO system was successful in 61% of all patients after a median
      device working period of 12.7 days; median ICU stay was 34 days and a survival
      rate of 64% of patients was achieved. Technical (8%) and device-associated
      bleeding (11%)/thromboembolic (8%) complication rates showed very acceptable
      levels. CONCLUSION: Our experience demonstrates that miniaturized, portable ECMO
      therapy allows location-independent, out-of-center stabilization of pulmonary
      compromised patients with consecutive inter-hospital transfer and further in
      house treatment, so that sophisticated ECMO therapy can be offered to every
      patient, even in hospitals with primary healthcare.

PMID- 24743550
TI  - Affinity proteomics reveals elevated muscle proteins in plasma of children with
      cerebral malaria.
AB  - Systemic inflammation and sequestration of parasitized erythrocytes are central
      processes in the pathophysiology of severe Plasmodium falciparum childhood
      malaria. However, it is still not understood why some children are more at risks
      to develop malaria complications than others. To identify human proteins in
      plasma related to childhood malaria syndromes, multiplex antibody suspension bead
      arrays were employed. Out of the 1,015 proteins analyzed in plasma from more than
      700 children, 41 differed between malaria infected children and community
      controls, whereas 13 discriminated uncomplicated malaria from severe malaria
      syndromes. Markers of oxidative stress were found related to severe malaria
      anemia while markers of endothelial activation, platelet adhesion and muscular
      damage were identified in relation to children with cerebral malaria. These
      findings suggest the presence of generalized vascular inflammation, vascular wall
      modulations, activation of endothelium and unbalanced glucose metabolism in
      severe malaria. The increased levels of specific muscle proteins in plasma
      implicate potential muscle damage and microvasculature lesions during the course
      of cerebral malaria. 

PMID- 24743551
TI  - Low-intensity pulsed ultrasound stimulation facilitates osteogenic
      differentiation of human periodontal ligament cells.
AB  - Human periodontal ligament cells (hPDLCs) possess stem cell properties, which
      play a key role in periodontal regeneration. Physical stimulation at appropriate
      intensities such as low-intensity pulsed ultrasound (LIPUS) enhances cell
      proliferation and osteogenic differentiation of mesechymal stem cells. However,
      the impacts of LIPUS on osteogenic differentiation of hPDLCs in vitro and its
      molecular mechanism are unknown. This study was undertaken to investigate the
      effects of LIPUS on osteogenic differentiation of hPDLCs. HPDLCs were isolated
      from premolars of adolescents for orthodontic reasons, and exposed to LIPUS at
      different intensities to determine an optimal LIPUS treatment dosage. Dynamic
      changes of alkaline phosphatase (ALP) activities in the cultured cells and
      supernatants, and osteocalcin production in the supernatants after treatment were
      analyzed. Runx2 and integrin beta1 mRNA levels were assessed by reverse
      transcription polymerase chain reaction analysis after LIPUS stimulation.
      Blocking antibody against integrinbeta1 was used to assess the effects of
      integrinbeta1 inhibitor on LIPUS-induced ALP activity, osteocalcin production as
      well as calcium deposition. Our data showed that LIPUS at the intensity of 90
      mW/cm2 with 20 min/day was more effective. The ALP activities in lysates and
      supernatants of LIPUS-treated cells started to increase at days 3 and 7,
      respectively, and peaked at day 11. LIPUS treatment significantly augmented the
      production of osteocalcin after day 5. LIPUS caused a significant increase in the
      mRNA expression of Runx2 and integrin beta1, while a significant decline when the
      integrinbeta1 inhibitor was used. Moreover, ALP activity, osteocalcin production
      as well as calcium nodules of cells treated with both daily LIPUS stimulation and
      integrinbeta1 antibody were less than those in the LIPUS-treated group. In
      conclusion, LIPUS promotes osteogenic differentiation of hPDLCs, which is
      associated with upregulation of Runx2 and integrin beta1, which may thus provide
      therapeutic benefits in periodontal tissue regeneration. 

PMID- 24743552
TI  - Logging concessions enable illegal logging crisis in the Peruvian Amazon.
AB  - The Peruvian Amazon is an important arena in global efforts to promote
      sustainable logging in the tropics. Despite recent efforts to achieve
      sustainability, such as provisions in the US-Peru Trade Promotion Agreement,
      illegal logging continues to plague the region. We present evidence that Peru's
      legal logging concession system is enabling the widespread illegal logging via
      the regulatory documents designed to ensure sustainable logging. Analyzing
      official government data, we found that 68.3% of all concessions supervised by
      authorities were suspected of major violations. Of the 609 total concessions,
      nearly 30% have been cancelled for violations and we expect this percentage to
      increase as investigations continue. Moreover, the nature of the violations
      indicate that the permits associated with legal concessions are used to harvest
      trees in unauthorized areas, thus threatening all forested areas. Many of the
      violations pertain to the illegal extraction of CITES-listed timber species
      outside authorized areas. These findings highlight the need for additional
      reforms. 

PMID- 24743553
TI  - Optical absorption and scattering properties of bulk porcine muscle phantoms from
      interstitial radiance measurements in 650-900 nm range.
AB  - We demonstrated the application of relative radiance-based continuous wave (cw)
      measurements for recovering absorption and scattering properties (the effective
      attenuation coefficient, the diffusion coefficient, the absorption coefficient
      and the reduced scattering coefficient) of bulk porcine muscle phantoms in the
      650-900 nm spectral range. Both the side-firing fiber (the detector) and the
      fiber with a spherical diffuser at the end (the source) were inserted
      interstitially at predetermined locations in the phantom. The porcine phantoms
      were prostate-shaped with ~4 cm in diameter and ~3 cm thickness and made from
      porcine loin or tenderloin muscles. The described method was previously validated
      using the diffusion approximation on simulated and experimental radiance data
      obtained for homogenous Intralipid-1% liquid phantom. The approach required
      performing measurements in two locations in the tissue with different distances
      to the source. Measurements were performed on 21 porcine phantoms. Spectral
      dependences of the effective attenuation and absorption coefficients for the loin
      phantom deviated from corresponding dependences for the tenderloin phantom for
      wavelengths <750 nm. The diffusion constant and the reduced scattering
      coefficient were very close for both phantom types. To quantify chromophore
      presence, the plot for the absorption coefficient was matched with a synthetic
      absorption spectrum constructed from deoxyhemoglobin, oxyhemoglobin and water.
      The closest match for the porcine loin spectrum was obtained with the following
      concentrations: 15.5 uM (+/-30% s.d.) Hb, 21 uM (+/-30% s.d.) HbO2 and 0.3 (+/
      30% s.d.) fractional volume of water. The tenderloin absorption spectrum was best
      described by 30 uM Hb (+/-30% s.d), 19 uM (+/-30% s.d.) HbO2 and 0.3 (+/-30%
      s.d.) fractional volume of water. The higher concentration of Hb in tenderloin
      was consistent with a dark-red appearance of the tenderloin phantom. The method
      can be applied to a number of biological tissues and organs for interstitial
      optical interrogation. 

PMID- 24743554
TI  - Increase in the number of tuberculosis cases treated following tuberculin skin
      testing in first-year schoolchildren in Madagascar.
AB  - BACKGROUND: Tuberculosis continues to cause unacceptably high levels of disease
      and death worldwide. Active preventive strategies are required to improve
      tuberculosis control and to increase the number of cases treated in developing
      countries. The aim of this study was to evaluate the utility of the tuberculin
      skin test (TST) in first-year schoolchildren as a means of increasing the number
      of tuberculosis cases detected through the screening of close contacts. METHODS:
      All members of the households of 90 schoolchildren assigned to three groups on
      the basis of TST category (<= 5 mm, [5-15)mm, >= 15 mm) were screened for sputum
      smear-positive pulmonary tuberculosis. The percentage detection of tuberculosis
      in close contacts was compared between TST categories. RESULTS: We identified 433
      close contacts of the 90 schoolchildren, who were then evaluated for
      tuberculosis. We identified 11 cases of pulmonary tuberculosis among the close
      contacts (7 already on treatment and 4 previously undiagnosed): 0 in TST category
      <= 5 mm, 3 in TST category [5-15) mm and 8 in TST category >= 15 mm). This
      approach increased the detection of tuberculosis cases by a factor of 1.6 in
      first-year schoolchildren of the TST >= 5 mm group. CONCLUSION: TST in first-year
      schoolchildren is a potentially effective method for improving the detection of
      tuberculosis in close contacts.

PMID- 24743555
TI  - Automatic 4D reconstruction of patient-specific cardiac mesh with 1-to-1 vertex
      correspondence from segmented contours lines.
AB  - We propose an automatic algorithm for the reconstruction of patient-specific
      cardiac mesh models with 1-to-1 vertex correspondence. In this framework, a
      series of 3D meshes depicting the endocardial surface of the heart at each time
      step is constructed, based on a set of border delineated magnetic resonance
      imaging (MRI) data of the whole cardiac cycle. The key contribution in this work
      involves a novel reconstruction technique to generate a 4D (i.e., spatial
      temporal) model of the heart with 1-to-1 vertex mapping throughout the time
      frames. The reconstructed 3D model from the first time step is used as a base
      template model and then deformed to fit the segmented contours from the
      subsequent time steps. A method to determine a tree-based connectivity
      relationship is proposed to ensure robust mapping during mesh deformation. The
      novel feature is the ability to handle intra- and inter-frame 2D topology changes
      of the contours, which manifests as a series of merging and splitting of contours
      when the images are viewed either in a spatial or temporal sequence. Our
      algorithm has been tested on five acquisitions of cardiac MRI and can
      successfully reconstruct the full 4D heart model in around 30 minutes per
      subject. The generated 4D heart model conforms very well with the input segmented
      contours and the mesh element shape is of reasonably good quality. The work is
      important in the support of downstream computational simulation activities. 

PMID- 24743556
TI  - Accumulated expression level of cytosolic glutamine synthetase 1 gene (OsGS1;1 or
      OsGS1;2) alter plant development and the carbon-nitrogen metabolic status in
      rice.
AB  - Maintaining an appropriate balance of carbon to nitrogen metabolism is essential
      for rice growth and yield. Glutamine synthetase is a key enzyme for ammonium
      assimilation. In this study, we systematically analyzed the growth phenotype,
      carbon-nitrogen metabolic status and gene expression profiles in GS1;1-, GS1;2
      overexpressing rice and wildtype plants. Our results revealed that the GS1;1-,
      GS1;2-overexpressing plants exhibited a poor plant growth phenotype and yield and
      decreased carbon/nitrogen ratio in the stem caused by the accumulation of
      nitrogen in the stem. In addition, the leaf SPAD value and photosynthetic
      parameters, soluble proteins and carbohydrates varied greatly in the GS1;1-,
      GS1;2-overexpressing plants. Furthermore, metabolite profile and gene expression
      analysis demonstrated significant changes in individual sugars, organic acids and
      free amino acids, and gene expression patterns in GS1;1-, GS1;2-overexpressing
      plants, which also indicated the distinct roles that these two GS1 genes played
      in rice nitrogen metabolism, particularly when sufficient nitrogen was applied in
      the environment. Thus, the unbalanced carbon-nitrogen metabolic status and poor
      ability of nitrogen transportation from stem to leaf in GS1;1-, GS1;2
      overexpressing plants may explain the poor growth and yield.

PMID- 24743557
TI  - Association between the polymorphism rs3217927 of CCND2 and the risk of childhood
      acute lymphoblastic leukemia in a Chinese population.
AB  - CyclinD proteins, the ultimate recipients of mitogenic and oncogenic signals,
      play a crucial role in cell-cycle regulation. CyclinD2, one of the cyclinD
      family, is overexpressed in T-acute lymphoblastic leukemia (ALL) and B-cell
      chronic lymphocytic leukemia and involved in the pathogenesis of leukemias.
      Recent reports indicated that CCND2 polymorphisms are associated with human
      cancer risk, thusly we hypothesized that CCND2 gene polymorphisms may contribute
      to childhood ALL susceptibility. We selected the polymorphism rs3217927 located
      in the 3'UTR region of CCND2 to assess its associations with childhood ALL risk
      in a case-control study. A significant difference was found in the genotype
      distributions of rs3217927 polymorphism between cases and controls (P = 0.019)
      and homozygous GG genotype may be an increased risk factor for childhood ALL
      (adjusted OR  =  1.84, 95% CI  =  1.14 -2.99). Furthermore, this increased risk
      was more pronounced with GG genotype among high-risk ALL (adjusted OR  = 1.95,
      95% CI  =  1.04-3.67), low-risk ALL (adjusted OR  =  2.09, 95% CI  =  1.13-3.87),
      B-phenotype ALL patients (adjusted OR  =  1.78, 95% CI  =  1.08-2.95) and T
      phenotype ALL patients (adjusted OR  =  2.87, 95% CI  =  1.16-7.13). Our results
      provide evidence that CCND2 polymorphism rs3217927 may be involved in the
      etiology of childhood ALL, and the GG genotype of rs3217927 may modulate the
      genetic susceptibility to childhood ALL in the Chinese population. Further
      functional studies and investigations in larger populations should be conducted
      to validate our findings. 

PMID- 24743558
TI  - Genomic and metabolic diversity of Marine Group I Thaumarchaeota in the
      mesopelagic of two subtropical gyres.
AB  - Marine Group I (MGI) Thaumarchaeota are one of the most abundant and cosmopolitan
      chemoautotrophs within the global dark ocean. To date, no representatives of this
      archaeal group retrieved from the dark ocean have been successfully cultured. We
      used single cell genomics to investigate the genomic and metabolic diversity of
      thaumarchaea within the mesopelagic of the subtropical North Pacific and South
      Atlantic Ocean. Phylogenetic and metagenomic recruitment analysis revealed that
      MGI single amplified genomes (SAGs) are genetically and biogeographically
      distinct from existing thaumarchaea cultures obtained from surface waters.
      Confirming prior studies, we found genes encoding proteins for aerobic ammonia
      oxidation and the hydrolysis of urea, which may be used for energy production, as
      well as genes involved in 3-hydroxypropionate/4-hydroxybutyrate and oxidative
      tricarboxylic acid pathways. A large proportion of protein sequences identified
      in MGI SAGs were absent in the marine cultures Cenarchaeum symbiosum and
      Nitrosopumilus maritimus, thus expanding the predicted protein space for this
      archaeal group. Identifiable genes located on genomic islands with low metagenome
      recruitment capacity were enriched in cellular defense functions, likely in
      response to viral infections or grazing. We show that MGI Thaumarchaeota in the
      dark ocean may have more flexibility in potential energy sources and adaptations
      to biotic interactions than the existing, surface-ocean cultures. 

PMID- 24743560
TI  - Thrombocytosis is associated with increased short and long term mortality after
      exacerbation of chronic obstructive pulmonary disease: a role for antiplatelet
      therapy?
AB  - INTRODUCTION: Evidence suggests that platelets play a significant role in
      inflammation in addition to their role in thrombosis. Systemic inflammation is
      linked to poor short and long term outcomes in COPD. Increased platelet
      activation has been reported in acute exacerbations of COPD (AECOPD). We
      investigated whether thrombocytosis is independently associated with poor
      outcomes following AECOPD. METHODS: An observational cohort study of patients
      hospitalised with AECOPD was performed. Patients were >40 years with spirometry
      confirmed COPD admitted between 2009 and 2011. Platelet count was recorded on
      admission. The primary outcome was 1-year all-cause mortality. Secondary outcomes
      included inhospital mortality and cardiovascular events. Analyses were conducted
      using logistic regression after adjustment for confounding variables. RESULTS:
      1343 patients (49% male) were included. Median age was 72 years (IQR 63-79
      years). 157 (11.7%) had thrombocytosis. Thrombocytosis was associated with both 1
      year mortality and inhospital mortality; OR 1.53 (95% CI 1.03 to 2.29, p=0.030)
      and OR 2.37 (95% CI 1.29 to 4.34, p=0.005), respectively. Cardiovascular
      hospitalisation was not significantly increased (OR 1.13 (95% CI 0.73 to 1.76,
      p=0.600)) in patients with thrombocytosis. Aspirin or clopidogrel treatment
      correlated with a reduction in 1-year mortality (OR 0.63 (95% CI 0.47 to 0.85,
      p=0.003)) but not inhospital mortality (OR 0.69 (95% CI 0.41 to 1.11, p=0.124)).
      CONCLUSIONS: After adjustment for confounders thrombocytosis was associated with
      increased 1-year mortality after exacerbation of COPD. Antiplatelet therapy was
      associated with significantly lower 1-year mortality and may have a protective
      role to play in patients with AECOPD.

PMID- 24743559
TI  - Viability of Pseudomonas aeruginosa in cough aerosols generated by persons with
      cystic fibrosis.
AB  - BACKGROUND: Person-to-person transmission of respiratory pathogens, including
      Pseudomonas aeruginosa, is a challenge facing many cystic fibrosis (CF) centres.
      Viable P aeruginosa are contained in aerosols produced during coughing, raising
      the possibility of airborne transmission. METHODS: Using purpose-built equipment,
      we measured viable P aeruginosa in cough aerosols at 1, 2 and 4 m from the
      subject (distance) and after allowing aerosols to age for 5, 15 and 45 min in a
      slowly rotating drum to minimise gravitational settling and inertial impaction
      (duration). Aerosol particles were captured and sized employing an Anderson
      Impactor and cultured using conventional microbiology. Sputum was also cultured
      and lung function and respiratory muscle strength measured. RESULTS: Nineteen
      patients with CF, mean age 25.8 (SD 9.2) years, chronically infected with P
      aeruginosa, and 10 healthy controls, 26.5 (8.7) years, participated. Viable P
      aeruginosa were detected in cough aerosols from all patients with CF, but not
      from controls; travelling 4 m in 17/18 (94%) and persisting for 45 min in 14/18
      (78%) of the CF group. Marked inter-subject heterogeneity of P aeruginosa aerosol
      colony counts was seen and correlated strongly (r=0.73-0.90) with sputum
      bacterial loads. Modelling decay of viable P aeruginosa in a clinic room
      suggested that at the recommended ventilation rate of two air changes per hour
      almost 50 min were required for 90% to be removed after an infected patient left
      the room. CONCLUSIONS: Viable P aeruginosa in cough aerosols travel further and
      last longer than recognised previously, providing additional evidence of airborne
      transmission between patients with CF.

PMID- 24743561
TI  - The devastating power of platelets in COPD exacerbations: can aspirin save lives
      in COPD?

PMID- 24743562
TI  - The beneficial effect of methylphenidate in ADHD with comorbid separation
      anxiety.
AB  - The objective of this study was to assess the response of subsyndromal separation
      anxiety (SSSA) symptoms to methylphenidate (MPH) treatment in patients with
      attention-deficit/hyperactivity disorder (ADHD). A group of patients with ADHD
      and SSSA (n=42), aged 8-17 years, received 12 weeks of MPH treatment. The
      severity of SSSA symptoms was assessed using appropriate scales including the
      Screen for Child Anxiety Related Emotional Disorders and the specially designed
      Child and Adolescent Separation Anxiety Scale (CASAS). The severity of ADHD
      symptoms was assessed using the ADHD Rating Scale. The severity of ADHD and
      separation anxiety reduced significantly and significant positive correlations
      were found between the changes in ADHD Rating Scale and the total CASAS scores
      (P=0.012), as well as other relevant subscales of Screen for Child Anxiety
      Related Emotional Disorders and CASAS. The MPH-related attenuation in the
      severity of ADHD was associated with a corresponding improvement in separation
      anxiety related to school. SSSA symptomatology may be secondary to ADHD and thus
      the alleviation in ADHD symptoms achieved by MPH treatment results in
      corresponding relief in separation anxiety. 

PMID- 24743563
TI  - Evolutionarily diverged regulation of X-chromosomal genes as a primal event in
      mouse reproductive isolation.
AB  - Improper gene regulation is implicated in reproductive isolation, but its genetic
      and molecular bases are unknown. We previously reported that a mouse inter
      subspecific X chromosome substitution strain shows reproductive isolation
      characterized by male-specific sterility due to disruption of meiotic entry in
      spermatogenesis. Here, we conducted comprehensive transcriptional profiling of
      the testicular cells of this strain by microarray. The results clearly revealed
      gross misregulation of gene expression in the substituted donor X chromosome.
      Such misregulation occurred prior to detectable spermatogenetic impairment,
      suggesting that it is a primal event in reproductive isolation. The misregulation
      of X-linked genes showed asymmetry; more genes were disproportionally
      downregulated rather than upregulated. Furthermore, this misregulation
      subsequently resulted in perturbation of global transcriptional regulation of
      autosomal genes, probably by cascading deleterious effects. Remarkably, this
      transcriptional misregulation was substantially restored by introduction of
      chromosome 1 from the same donor strain as the X chromosome. This finding implies
      that one of regulatory genes acting in trans for X-linked target genes is located
      on chromosome 1. This study collectively suggests that regulatory incompatibility
      is a major cause of reproductive isolation in the X chromosome substitution
      strain. 

PMID- 24743565
TI  - Toward reliable estimates of abundance: comparing index methods to assess the
      abundance of a Mammalian predator.
AB  - Due to time and financial constraints indices are often used to obtain landscape
      scale estimates of relative species abundance. Using two different field methods
      and comparing the results can help to detect possible bias or a non monotonic
      relationship between the index and the true abundance, providing more reliable
      results. We used data obtained from camera traps and feces counts to
      independently estimate relative abundance of red foxes in the Black Forest, a
      forested landscape in southern Germany. Applying negative binomial regression
      models, we identified landscape parameters that influence red fox abundance,
      which we then used to predict relative red fox abundance. We compared the
      estimated regression coefficients of the landscape parameters and the predicted
      abundance of the two methods. Further, we compared the costs and the precision of
      the two field methods. The predicted relative abundances were similar between the
      two methods, suggesting that the two indices were closely related to the true
      abundance of red foxes. For both methods, landscape diversity and edge density
      best described differences in the indices and had positive estimated effects on
      the relative fox abundance. In our study the costs of each method were of similar
      magnitude, but the sample size obtained from the feces counts (262 transects) was
      larger than the camera trap sample size (88 camera locations). The precision of
      the camera traps was lower than the precision of the feces counts. The approach
      we applied can be used as a framework to compare and combine the results of two
      or more different field methods to estimate abundance and by this enhance the
      reliability of the result. 

PMID- 24743564
TI  - Impact of different oseltamivir regimens on treating influenza A virus infection
      and resistance emergence: insights from a modelling study.
AB  - Several studies have proven oseltamivir to be efficient in reducing influenza
      viral titer and symptom intensity. However, the usefulness of oseltamivir can be
      compromised by the emergence and spread of drug-resistant virus. The selective
      pressure exerted by different oseltamivir therapy regimens have received little
      attention. Combining models of drug pharmacokinetics, pharmacodynamics, viral
      kinetics and symptom dynamics, we explored the efficacy of oseltamivir in
      reducing both symptoms (symptom efficacy) and viral load (virological efficacy).
      We simulated samples of 1000 subjects using previously estimated between-subject
      variability in viral and symptom dynamic parameters to describe the observed
      heterogeneity in a patient population. We simulated random mutations conferring
      resistance to oseltamivir. We explored the effect of therapy initiation time,
      dose, intake frequency and therapy duration on influenza infection, illness
      dynamics, and emergence of viral resistance. Symptom and virological efficacies
      were strongly associated with therapy initiation time. The proportion of subjects
      shedding resistant virus was 27-fold higher when prophylaxis was initiated during
      the incubation period compared with no treatment. It fell to below 1% when
      treatment was initiated after symptom onset for twice-a-day intakes. Lower doses
      and prophylaxis regimens led to lower efficacies and increased risk of resistance
      emergence. We conclude that prophylaxis initiated during the incubation period is
      the main factor leading to resistance emergence. 

PMID- 24743566
TI  - Meta-analysis: narrow band imaging for diagnosis of gastric intestinal
      metaplasia.
AB  - BACKGROUND: Distinguishing early gastric cancer is challenging with current
      imaging techniques. Narrow band imaging (NBI) is effective for characterizing
      gastric lesions. OBJECTIVES: The aim of this meta-analysis was to estimate the
      diagnostic accuracy of NBI in the gastric intestinal metaplasia (GIM). METHODS:
      We performed data analysis using Meta-DiSc (version 1.4) and STATA (version 11.0)
      software. To assess study quality and potential for bias, we used the Quality
      Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool. RESULTS: Six studies
      involving 347 patients were included. On a per-patient basis, the sensitivity of
      NBI for diagnosis of GIM was 0.65 (95% CI  =  0.56-0.74), and the specificity was
      0.93 (95% CI  =  0.88-0.97). The area under the summary receiver operating
      characteristic (SROC) curve was 0.8731. However, on a per-lesion basis, the
      sensitivity and specificity of NBI were 0.69 (95% CI  =  0.63-0.74) and 0.91 (95%
      CI  =  0.87-0.94), respectively. The SROC was 0.9009. The pooled sensitivity and
      specificity of magnification endoscopy (NBI-ME) were 0.76 (95% CI  =  0.61-0.87)
      and 0.89 (95% CI  =  0.80-0.94), respectively, on per-patient analysis. On a per
      lesion basis, the pooled sensitivity and specificity of NBI-ME were 0.84 (95% CI 
      =  0.76-0.89) and 0.93 (95% CI  =  0.89-0.96), respectively. Heterogeneity was
      observed with an I2 for diagnostic odds ratio (DOR) of 0.01% and 85.8%,
      respectively. There was no statistical significance for the evaluation of
      publication bias. CONCLUSIONS: Our meta-analysis shows that NBI is a useful tool
      for differential diagnosis of GIM with relatively low sensitivity and high
      specificity.

PMID- 24743567
TI  - Change of floral orientation within an inflorescence affects pollinator behavior
      and pollination efficiency in a bee-pollinated plant, Corydalis sheareri.
AB  - Vertical raceme or spike inflorescences that are bee-pollinated tend to present
      their flowers horizontally. Horizontal presentation of flowers is hypothesized to
      enhance pollinator recognition and pollination precision, and it may also ensure
      greater consistency of pollinator movement on inflorescences. We tested the
      hypotheses using bee-pollinated Corydalis sheareri which has erect inflorescences
      consisting of flowers with horizontal orientation. We altered the orientation of
      individual flowers and prepared three types of inflorescences: (i) unmanipulated
      inflorescences with horizontal-facing flowers, (ii) inflorescences with flowers
      turned upward, and (iii) inflorescences with flowers turned downward. We compared
      number of inflorescences approached and visited, number of successive probes
      within an inflorescence, the direction percentage of vertical movement on
      inflorescences, efficiency of pollen removal and seed production per
      inflorescence. Deviation from horizontal orientation decreased both approaches
      and visits by leafcutter bees and bumble bees to inflorescences. Changes in
      floral orientation increased the proportion of downward movements by leafcutter
      bees and decreased the consistency of pollinator movement on inflorescences. In
      addition, pollen removal per visit and seed production per inflorescence also
      declined with changes of floral orientation. In conclusion, floral orientation
      seems more or less optimal as regards bee behavior and pollen transfer for
      Corydalis sheareri. A horizontal orientation may be under selection of
      pollinators and co-adapt with other aspects of the inflorescence and floral
      traits.

PMID- 24743568
TI  - Interleukin-32gamma transgenic mice resist LPS-mediated septic shock.
AB  - Interleukin-32 (IL-32) is a cytokine and inducer of various proinflammatory
      cytokines such as TNFalpha, IL-1beta, and IL-6 as well as chemokines. There are
      five splicing variants (alpha, beta, gamma, delta, and epsilon) and IL-32gamma is
      the most active isoform. We generated human IL-32gamma transgenic (IL-32gamma TG)
      mice to express high level of IL-32gamma in various tissues, including immune
      cells. The pathology of sepsis is based on the systemic inflammatory response
      that is characterized by upregulating inflammatory cytokines in whole body,
      particularly in response to gram-negative bacteria. We investigated the role of
      IL-32gamma in a mouse model of experimental sepsis by using lipopolysaccharides
      (LPS). We found that IL-32gammaTG mice resisted LPS-induced lethal endotoxemia.
      IL-32gamma reduced systemic cytokines release after LPS administration but not
      the local immune response. IL-32gammaTG increased neutrophil influx into the
      initial foci of the primary injected site, and prolonged local cytokines and
      chemokines production. These results suggest that neutrophil recruitment in IL
      32gammaTG occurred as a result of the local induction of chemokines but not the
      systemic inflammatory cytokine circulation. Together, our results suggest that IL
      32gamma enhances an innate immune response against local infection but inhibits
      the spread of immune responses, leading to systemic immune disorder.

PMID- 24743569
TI  - Evaluation of galactomannan enzyme immunoassay and quantitative real-time PCR for
      the diagnosis of invasive pulmonary aspergillosis in a rat model.
AB  - Since there is no consensus about the most reliable assays to detect invasive
      aspergillosis from samples obtained by minimally invasive or noninvasive methods,
      we compared the efficacy of an enzyme-linked immunosorbent assay (ELISA) for
      galactomannan (GM) detection and quantitative real-time PCR assay (qRT-PCR) for
      the diagnosis of invasive pulmonary aspergillosis. Neutropenic, male Sprague
      Dawley rats (specific pathogen free; 8 weeks old; weight, 200 +/- 20 g) were
      immunosuppressed with cyclophosphamide and infected with Aspergillus fumigatus
      intratracheally. Tissue and whole blood samples were harvested on days 1, 3, 5,
      and 7 post-infection and examined with GM ELISA and qRT-PCR. The A. fumigatus DNA
      detection sequence was detected in the following number of samples from 12
      immunosuppressed, infected rats examined on the scheduled days: day 1 (0/12), day
      3 (0/12), day 5 (6/12), and day 7 (8/12) post-infection. The sensitivity and
      specificity of the qRT-PCR assay was 29.2% and 100%, respectively. Receiver
      operating characteristic curve (ROC) analysis indicated a Ct (cycle threshold)
      cut-off value of 15.35, and the area under the curve (AUC) was 0.627. The GM
      assay detected antigen in sera obtained on day 1 (5/12), day 3 (9/ 12), day 5
      (12/12), and day 7 (12/12) post-infection, and thus had a sensitivity of 79.2%
      and a specificity of 100%. The ROC of the GM assay indicated that the optimal Ct
      cut-off value was 1.40 (AUC, 0.919). The GM assay was more sensitive than the qRT
      PCR assay in diagnosing invasive pulmonary aspergillosis in rats. 

PMID- 24743570
TI  - Hsp20, a small heat shock protein of Deinococcus radiodurans, confers tolerance
      to hydrogen peroxide in Escherichia coli.
AB  - The present study shows that DR1114 (Hsp20), a small heat shock protein of the
      radiationresistant bacterium Deinococcus radiodurans, enhances tolerance to
      hydrogen peroxide (H2O2) stress when expressed in Escherichia coli. A protein
      profile comparison showed that E. coli cells overexpressing D. radiodurans Hsp20
      (EC-pHsp20) activated the redox state proteins, thus maintaining redox
      homeostasis. The cells also showed increased expression of pseudouridine (psi)
      synthases, which are important to the stability and proper functioning of
      structural RNA molecules. We found that the D. radiodurans mutant strain, which
      lacks a psi synthase (DR0896), was more sensitive to H2O2 stress than wild type.
      These suggest that an increased expression of proteins involved in the control of
      redox state homeostasis along with more stable ribosomal function may explain the
      improved tolerance of EC-pHsp20 to H2O2 stress.

PMID- 24743571
TI  - Senior Thai fecal microbiota comparison between vegetarians and non-vegetarians
      using PCR-DGGE and real-time PCR.
AB  - The fecal microbiotas were investigated in 13 healthy Thai subjects using
      polymerase chain reaction denaturing gradient gel electrophoresis (PCR-DGGE).
      Among the 186 DNA bands detected on the polyacrylamide gel, 37 bands were
      identified as representing 11 species: Bacteroides thetaiotaomicron, Bacteroides
      ovatus, Bacteroides uniformis, Bacteroides vulgatus, Clostridium colicanis,
      Eubacterium eligenes, E. rectale, Faecalibacterium prausnitzii, Megamonas
      funiformis, Prevotella copri, and Roseburia intestinalis, belonging mainly to the
      groups of Bacteroides, Prevotella, Clostridium, and F. prausnitzii. A dendrogram
      of the PCR-DGGE divided the subjects; vegetarians and non-vegetarians. The fecal
      microbiotas were also analyzed using a quantitative real-time PCR focused on
      Bacteroides, Bifidobacterium, Enterobacteriaceae, Clostrium coccoides-Eubacterium
      rectale, C. leptum, Lactobacillus, and Prevotella. The nonvegetarian and
      vegetarian subjects were found to have significant differences in the high
      abundance of the Bacteroides and Prevotella genera, respectively. No significant
      differences were found in the counts of Bifidabacterium, Enterobacteriaceae, C.
      coccoides-E. rectale group, C. leptum group, and Lactobacillus. Therefore, these
      findings on the microbiota of healthy Thais consuming different diets could
      provide helpful data for predicting the health of South East Asians with similar
      diets.

PMID- 24743572
TI  - Evaluation of beta-1,4-endoglucanases produced by bacilli isolated from paper and
      pulp mill effluents irrigated soil.
AB  - A total of 10 cellulase-producing bacteria were isolated from soil samples
      irrigated with paper and pulp mill effluents. The sequencing of 16S rRNA gene
      revealed that all isolates belonged to different species of genus Bacillus. Among
      the different isolates, B. subtilis IARI-SP-1 exhibited a high degree of beta-1,4
      endoglucanase (2.5 IU/ml), beta-1,4-exoglucanase (0.8 IU/ml), and beta
      glucosidase (0.084 IU/ml) activity, followed by B. amyloliquefaciens IARI-SP-2.
      CMC was found to be the best carbon source for production of endo/exoglucanase
      and beta-glucosidase. The beta-1,4-endoglucanase gene was amplified from all
      isolates and their deduced amino acid sequences belonged to glycosyl hydrolase
      family 5. Among the domains of different isolates, the catalytic domains
      exhibited the highest homology of 93.7%, whereas the regions of signal, leader,
      linker, and carbohydrate-binding domain indicated low homology (73-74%). These
      variations in sequence homology are significant and could contribute to the
      structure and function of the enzyme. 

PMID- 24743573
TI  - Overexpression of aprE2, a fibrinolytic enzyme gene from Bacillus subtilis CH3-5,
      in Escherichia coli and the properties of AprE2.
AB  - The aprE2 gene with its prosequence from Bacillus subtilis CH3-5 was
      overexpressed in Escherichia coli BL21(DE3) by using plasmid pET26b(+). After
      IPTG induction, active and mature AprE2 was produced when cells were grown at 20
      degrees C, whereas inactive and insoluble enzyme was produced in a large amount
      when cells were grown at 37 degrees C. The insoluble fraction was resuspended
      with 6 M guanidine-HCl and dialyzed against 2 M Tris-HCl (pH 7.0) or 0.5 M sodium
      acetate (pH 7.0) buffer. Then active AprE2 was regenerated and purified by a Ni
      NTA column. Purified AprE2 from the soluble fraction had a specific activity of
      1,069.4 +/- 42.4 U/mg protein, higher than that from the renatured insoluble
      fraction. However, more active AprE2 was obtained by renaturation of the
      insoluble fraction. AprE2 was most stable at pH 7 and 40 degrees C, respectively.
      The fibrinolytic activity of AprE2 was inhibited by PMSF, but not by EDTA and
      metal ions. AprE2 degraded Aalpha and Bbeta chains of fibrinogen quickly, but not
      the gamma-chain. AprE2 exhibited the highest specificity for N-succinyl-Ala-Ala
      Pro-Phe-pNA. The Km and kcat/Km of AprE2 was 0.56 mM and 3.10 * 10(4) S(-1) M(
      1), respectively. 

PMID- 24743575
TI  - When top-down becomes bottom up: behaviour of hyperdense howler monkeys (Alouatta
      seniculus) trapped on a 0.6 ha island.
AB  - Predators are a ubiquitous presence in most natural environments. Opportunities
      to contrast the behaviour of a species in the presence and absence of predators
      are thus rare. Here we report on the behaviour of howler monkey groups living
      under radically different conditions on two land-bridge islands in Lago Guri,
      Venezuela. One group of 6 adults inhabited a 190-ha island (Danto) where they
      were exposed to multiple potential predators. This group, the control, occupied a
      home range of 23 ha and contested access to food resources with neighbouring
      groups in typical fashion. The second group, containing 6 adults, was isolated on
      a remote, predator-free 0.6 ha islet (Iguana) offering limited food resources.
      Howlers living on the large island moved, fed and rested in a coherent group,
      frequently engaged in affiliative activities, rarely displayed agonistic
      behaviour and maintained intergroup spacing through howling. In contrast, the
      howlers on Iguana showed repulsion, as individuals spent most of their time
      spaced widely around the perimeter of the island. Iguana howlers rarely engaged
      in affiliative behaviour, often chased or fought with one another and were not
      observed to howl. These behaviors are interpreted as adjustments to the
      unrelenting deprivation associated with bottom-up limitation in a predator-free
      environment. 

PMID- 24743574
TI  - Curcumin significantly enhances dual PI3K/Akt and mTOR inhibitor NVP-BEZ235
      induced apoptosis in human renal carcinoma Caki cells through down-regulation of
      p53-dependent Bcl-2 expression and inhibition of Mcl-1 protein stability.
AB  - The PI3K/Akt and mTOR signaling pathways are important for cell survival and
      growth, and they are highly activated in cancer cells compared with normal cells.
      Therefore, these signaling pathways are targets for inducing cancer cell death.
      The dual PI3K/Akt and mTOR inhibitor NVP-BEZ235 completely inhibited both
      signaling pathways. However, NVP-BEZ235 had no effect on cell death in human
      renal carcinoma Caki cells. We tested whether combined treatment with natural
      compounds and NVP-BEZ235 could induce cell death. Among several chemopreventive
      agents, curcumin, a natural biologically active compound that is extracted from
      the rhizomes of Curcuma species, markedly induced apoptosis in NVP-BEZ235-treated
      cells. Co-treatment with curcumin and NVP-BEZ235 led to the down-regulation of
      Mcl-1 protein expression but not mRNA expression. Ectopic expression of Mcl-1
      completely inhibited curcumin plus NVP-NEZ235-induced apoptosis. Furthermore, the
      down-regulation of Bcl-2 was involved in curcumin plus NVP-BEZ235-induced
      apoptosis. Curcumin or NVP-BEZ235 alone did not change Bcl-2 mRNA or protein
      expression, but co-treatment reduced Bcl-2 mRNA and protein expression. Combined
      treatment with NVP-BEZ235 and curcumin reduced Bcl-2 expression in wild-type p53
      HCT116 human colon carcinoma cells but not p53-null HCT116 cells. Moreover, Bcl-2
      expression was completely reversed by treatment with pifithrin-alpha, a p53
      specific inhibitor. Ectopic expression of Bcl-2 also inhibited apoptosis in NVP
      BE235 plus curcumin-treated cells. In contrast, NVP-BEZ235 combined with curcumin
      did not have a synergistic effect on normal human skin fibroblasts and normal
      human mesangial cells. Taken together, combined treatment with NVP-BEZ235 and
      curcumin induces apoptosis through p53-dependent Bcl-2 mRNA down-regulation at
      the transcriptional level and Mcl-1 protein down-regulation at the post
      transcriptional level.

PMID- 24743576
TI  - Mental representation and mental practice: experimental investigation on the
      functional links between motor memory and motor imagery.
AB  - Recent research on mental representation of complex action has revealed distinct
      differences in the structure of representational frameworks between experts and
      novices. More recently, research on the development of mental representation
      structure has elicited functional changes in novices' representations as a result
      of practice. However, research investigating if and how mental practice adds to
      this adaptation process is lacking. In the present study, we examined the
      influence of mental practice (i.e., motor imagery rehearsal) on both putting
      performance and the development of one's representation of the golf putt during
      early skill acquisition. Novice golfers (N = 52) practiced the task of golf
      putting under one of four different practice conditions: mental, physical, mental
      physical combined, and no practice. Participants were tested prior to and after a
      practice phase, as well as after a three day retention interval. Mental
      representation structures of the putt were measured, using the structural
      dimensional analysis of mental representation. This method provides psychometric
      data on the distances and groupings of basic action concepts in long-term memory.
      Additionally, putting accuracy and putting consistency were measured using two
      dimensional error scores of each putt. Findings revealed significant performance
      improvements over the course of practice together with functional adaptations in
      mental representation structure. Interestingly, after three days of practice, the
      mental representations of participants who incorporated mental practice into
      their practice regime displayed representation structures that were more similar
      to a functional structure than did participants who did not incorporate mental
      practice. The findings of the present study suggest that mental practice promotes
      the cognitive adaptation process during motor learning, leading to more elaborate
      representations than physical practice only. 

PMID- 24743577
TI  - Spinal loads during cycling on an ergometer.
AB  - Cycling on an ergometer is an effective exercise for improving fitness. However,
      people with back problems or previous spinal surgery are often not aware of
      whether cycling could be harmful for them. To date, little information exists
      about spinal loads during cycling. A telemeterized vertebral body replacement
      allows in vivo measurement of implant loads during the activities of daily
      living. Five patients with a severe compression fracture of a lumbar vertebral
      body received these implants. During one measurement session, four of the
      participants exercised on a bicycle ergometer at various power levels. As the
      power level increased, the maximum resultant force and the difference between the
      maximum and minimum force (force range) during each pedal revolution increased.
      The average maximum-force increases between the two power levels 25 and 85 W were
      73, 84, 225 and 75 N for the four patients. The corresponding increases in the
      force range during a pedal revolution were 84, 98, 166 and 101 N. There were
      large variations in the measured forces between the patients and also within the
      same patient, especially for high power levels. In two patients, the maximum
      forces during high-power cycling were higher than the forces during walking
      measured on the same day. Therefore, the authors conclude that patients with back
      problems should not cycle at high power levels shortly after surgery as a
      precaution.

PMID- 24743580
TI  - Dispersal behavior of Tetranychus evansi and T. urticae on tomato at several
      spatial scales and densities: implications for integrated pest management.
AB  - Studying distribution is necessary to understand and manage the dynamics of
      species with spatially structured populations. Here we studied the distribution
      in Tetranychus evansi and T. urticae, two mite pests of tomato, in the scope of
      evaluating factors that can influence the effectiveness of Integrated Pest
      Management strategies. We found greater positive density-dependent distribution
      with T. evansi than T. urticae when assayed on single, detached tomato leaves.
      Indeed, T. evansi distribution among leaflets increased with initial population
      density while it was high even at low T. urticae densities. Intensity and rate of
      damage to whole plants was higher with T. evansi than T. urticae. We further
      studied the circadian migration of T. evansi within plant. When T. evansi density
      was high the distribution behavior peaked between 8 am and 3 pm and between 8 pm
      and 3 am local time of Kenya. Over 24 h the total number of mites ascending and
      descending was always similar and close to the total population size. The
      gregarious behavior of T. evansi combined with its rapid population growth rate,
      may explain why few tomato plants can be severely damaged by T. evansi and how
      suddenly all the crop can be highly infested. However the localisation and
      elimination of the first infested plants damaged by T. evansi could reduce the
      risk of outbreaks in the entire crop. These findings suggest also that an
      acaricide treated net placed on the first infested plants could be very effective
      to control T. evansi. Moreover circadian migration would therefore accentuate the
      efficiency of an acaricide treated net covering the infested plants. 

PMID- 24743579
TI  - Limb remote ischemic preconditioning attenuates lung injury after pulmonary
      resection under propofol-remifentanil anesthesia: a randomized controlled study.
AB  - BACKGROUND: Remote ischemic preconditioning (RIPC) may confer the protection in
      critical organs. The authors hypothesized that limb RIPC would reduce lung injury
      in patients undergoing pulmonary resection. METHODS: In a randomized,
      prospective, parallel, controlled trial, 216 patients undergoing elective
      thoracic pulmonary resection under one-lung ventilation with propofol
      remifentanil anesthesia were randomized 1:1 to receive either limb RIPC or
      conventional lung resection (control). Three cycles of 5-min ischemia/5-min
      reperfusion induced by a blood pressure cuff served as RIPC stimulus. The primary
      outcome was PaO2/FIO2. Secondary outcomes included other pulmonary variables, the
      incidence of in-hospital complications, markers of oxidative stress, and
      inflammatory response. RESULTS: Limb RIPC significantly increased PaO2/FIO2
      compared with control at 30 and 60 min after one-lung ventilation, 30 min after
      re-expansion, and 6 h after operation (238 +/- 52 vs. 192 +/- 67, P = 0.03; 223
      +/- 66 vs. 184 +/- 64, P = 0.01; 385 +/- 61 vs. 320 +/- 79, P = 0.003; 388 +/- 52
      vs. 317 +/- 46, P = 0.001, respectively). In comparison with control, it also
      significantly reduced serum levels of interleukin-6 and tumor necrosis factor
      alpha at 6, 12, 24, and 48 h after operation and malondialdehyde levels at 60 min
      after one-lung ventilation and 30 min after re-expansion (all P < 0.01). The
      incidence of acute lung injury and the length of postoperative hospital stay were
      markedly reduced by limb RIPC compared with control (all P < 0.05). CONCLUSION:
      Limb RIPC attenuates acute lung injury via improving intraoperative pulmonary
      oxygenation in patients without severe pulmonary disease after lung resection
      under propofol-remifentanil anesthesia.

PMID- 24743578
TI  - Identification of verrucarin a as a potent and selective steroid receptor
      coactivator-3 small molecule inhibitor.
AB  - Members of the steroid receptor coactivator (SRC) family are overexpressed in
      numerous types of cancers. In particular, steroid receptor coactivator 3 (SRC-3)
      has been recognized as a critical coactivator associated with tumor initiation,
      progression, recurrence, metastasis, and chemoresistance where it interacts with
      multiple nuclear receptors and other transcription factors to enhance their
      transcriptional activities and facilitate cross-talk between pathways that
      stimulate cancer progression. Because of its central role as an integrator of
      growth signaling pathways, development of small molecule inhibitors (SMIs)
      against SRCs have the potential to simultaneously disrupt multiple signal
      transduction networks and transcription factors involved in tumor progression.
      Here, high-throughput screening was performed to identify compounds able to
      inhibit the intrinsic transcriptional activities of the three members of the SRC
      family. Verrucarin A was identified as a SMI that can selectively promote the
      degradation of the SRC-3 protein, while affecting SRC-1 and SRC-2 to a lesser
      extent and having no impact on CARM-1 and p300 protein levels. Verrucarin A was
      cytotoxic toward multiple types of cancer cells at low nanomolar concentrations,
      but not toward normal liver cells. Moreover, verrucarin A was able to inhibit
      expression of the SRC-3 target genes MMP2 and MMP13 and attenuated cancer cell
      migration. We found that verrucarin A effectively sensitized cancer cells to
      treatment with other anti-cancer drugs. Binding studies revealed that verrucarin
      A does not bind directly to SRC-3, suggesting that it inhibits SRC-3 through its
      interaction with an upstream effector. In conclusion, unlike other SRC SMIs
      characterized by our laboratory that directly bind to SRCs, verrucarin A is a
      potent and selective SMI that blocks SRC-3 function through an indirect
      mechanism. 

PMID- 24743581
TI  - An integrated study to analyze soil microbial community structure and metabolic
      potential in two forest types.
AB  - Soil microbial metabolic potential and ecosystem function have received little
      attention owing to difficulties in methodology. In this study, we selected
      natural mature forest and natural secondary forest and analyzed the soil
      microbial community and metabolic potential combing the high-throughput
      sequencing and GeoChip technologies. Phylogenetic analysis based on 16S rRNA
      sequencing showed that one known archaeal phylum and 15 known bacterial phyla as
      well as unclassified phylotypes were presented in these forest soils, and
      Acidobacteria, Protecobacteria, and Actinobacteria were three of most abundant
      phyla. The detected microbial functional gene groups were related to different
      biogeochemical processes, including carbon degradation, carbon fixation, methane
      metabolism, nitrogen cycling, phosphorus utilization, sulfur cycling, etc. The
      Shannon index for detected functional gene probes was significantly higher
      (P<0.05) at natural secondary forest site. The regression analysis showed that a
      strong positive (P<0.05) correlation was existed between the soil microbial
      functional gene diversity and phylogenetic diversity. Mantel test showed that
      soil oxidizable organic carbon, soil total nitrogen and cellulose, glucanase, and
      amylase activities were significantly linked (P<0.05) to the relative abundance
      of corresponded functional gene groups. Variance partitioning analysis showed
      that a total of 81.58% of the variation in community structure was explained by
      soil chemical factors, soil temperature, and plant diversity. Therefore, the
      positive link of soil microbial structure and composition to functional activity
      related to ecosystem functioning was existed, and the natural secondary forest
      soil may occur the high microbial metabolic potential. Although the results can't
      directly reflect the actual microbial populations and functional activities, this
      study provides insight into the potential activity of the microbial community and
      associated feedback responses of the terrestrial ecosystem to environmental
      changes. 

PMID- 24743582
TI  - Mouse pulmonary adenoma susceptibility 1 locus is an expression QTL modulating
      Kras-4A.
AB  - Pulmonary adenoma susceptibility 1 (Pas1) is the major locus responsible for lung
      tumor susceptibility in mice; among the six genes mapping in this locus, Kras is
      considered the best candidate for Pas1 function although how it determines tumor
      susceptibility remains unknown. In an (A/J * C57BL/6)F4 intercross population
      treated with urethane to induce lung tumors, Pas1 not only modulated tumor
      susceptibility (LOD score = 48, 69% of phenotypic variance explained) but also
      acted, in lung tumor tissue, as an expression quantitative trait locus (QTL) for
      Kras-4A, one of two alternatively spliced Kras transcripts, but not Kras-4B.
      Additionally, Kras-4A showed differential allelic expression in lung tumor tissue
      of (A/J * C57BL/6)F4 heterozygous mice, with significantly higher expression from
      the A/J-derived allele; these results suggest that cis-acting elements control
      Kras-4A expression. In normal lung tissue from untreated mice of the same cross,
      Kras-4A levels were also highly linked to the Pas1 locus (LOD score = 23.2, 62%
      of phenotypic variance explained) and preferentially generated from the A/J
      derived allele, indicating that Pas1 is an expression QTL in normal lung tissue
      as well. Overall, the present findings shed new light on the genetic mechanism by
      which Pas1 modulates the susceptibility to lung tumorigenesis, through the fine
      control of Kras isoform levels.

PMID- 24743583
TI  - The expanding functions of cellular helicases: the tombusvirus RNA replication
      enhancer co-opts the plant eIF4AIII-like AtRH2 and the DDX5-like AtRH5 DEAD-box
      RNA helicases to promote viral asymmetric RNA replication.
AB  - Replication of plus-strand RNA viruses depends on recruited host factors that aid
      several critical steps during replication. Several of the co-opted host factors
      bind to the viral RNA, which plays multiple roles, including mRNA function, as an
      assembly platform for the viral replicase (VRC), template for RNA synthesis, and
      encapsidation during infection. It is likely that remodeling of the viral RNAs
      and RNA-protein complexes during the switch from one step to another requires RNA
      helicases. In this paper, we have discovered a second group of cellular RNA
      helicases, including the eIF4AIII-like yeast Fal1p and the DDX5-like Dbp3p and
      the orthologous plant AtRH2 and AtRH5 DEAD box helicases, which are co-opted by
      tombusviruses. Unlike the previously characterized DDX3-like AtRH20/Ded1p
      helicases that bind to the 3' terminal promoter region in the viral minus-strand
      (-)RNA, the other class of eIF4AIII-like RNA helicases bind to a different cis
      acting element, namely the 5' proximal RIII(-) replication enhancer (REN) element
      in the TBSV (-)RNA. We show that the binding of AtRH2 and AtRH5 helicases to the
      TBSV (-)RNA could unwind the dsRNA structure within the RIII(-) REN. This unique
      characteristic allows the eIF4AIII-like helicases to perform novel pro-viral
      functions involving the RIII(-) REN in stimulation of plus-strand (+)RNA
      synthesis. We also show that AtRH2 and AtRH5 helicases are components of the
      tombusvirus VRCs based on co-purification experiments. We propose that eIF4AIII
      like helicases destabilize dsRNA replication intermediate within the RIII(-) REN
      that promotes bringing the 5' and 3' terminal (-)RNA sequences in close vicinity
      via long-range RNA-RNA base pairing. This newly formed RNA structure promoted by
      eIF4AIII helicase together with AtRH20 helicase might facilitate the recycling of
      the viral replicases for multiple rounds of (+)-strand synthesis, thus resulting
      in asymmetrical viral replication. 

PMID- 24743585
TI  - ProCESS trial recalls Sir William Osler's advice.

PMID- 24743584
TI  - STOP!: a randomised, double-blind, placebo-controlled study of the efficacy and
      safety of methoxyflurane for the treatment of acute pain.
AB  - OBJECTIVE: To evaluate the short-term efficacy and safety of methoxyflurane for
      the treatment of acute pain in patients presenting to an emergency department
      (ED) with minor trauma. METHODS: STOP! was a randomised, double-blind,
      multicentre, placebo-controlled study conducted at six sites in the UK. A total
      of 300 patients, 90 of whom were adolescent patients (age 12-17 years), were
      randomised 150:150 to receive either methoxyflurane via a Penthrox inhaler or
      placebo. The primary end point of the study was the change in pain intensity as
      measured using the visual analogue scale (VAS) from baseline to 5, 10, 15 and 20
      min after the start of study drug inhalation. Patients were supplied with one
      inhaler containing 3 mL methoxyflurane or 5 mL placebo after enrolment and
      initial assessments. Age group (adolescent/adult) and baseline VAS score were
      controlled for in the statistical analyses. RESULTS: A total of 149 patients
      received methoxyflurane, and 149 patients received placebo. Demographic and
      baseline characteristics were comparable between the groups. Methoxyflurane
      reduced pain severity significantly more than placebo (p<0.0001) at all time
      points tested, with the greatest estimated treatment effect of -18.5 mm (adjusted
      change from baseline) seen at 15 min after the start of treatment. Methoxyflurane
      was well tolerated, with the majority of adverse reactions being mild, transient
      and in line with anticipated pharmacological action. CONCLUSION: The results of
      this study suggest that methoxyflurane administered via the Penthrox inhaler is
      an efficacious, safe, and rapidly acting analgesic. TRIAL REGISTRATION NUMBER:
      NCT01420159.

PMID- 24743586
TI  - Methoxyflurane is a better painkiller than placebo: but do we want to know more?

PMID- 24743587
TI  - Extrication time prediction tool.
AB  - BACKGROUND: Many patients will require extrication following a motor vehicle
      collision (MVC). Little information exists on the time taken for extrication or
      the factors which affect this time. OBJECTIVE: To derive a tool to predict the
      time taken to extricate patients from MVCs. METHODS: A prospective, observational
      derivation study was carried out in the West Midland Fire Service's metropolitan
      area. An expert group identified factors that may predict extrication time-the
      presence and absence of these factors was prospectively recorded at eligible
      extrications for the study period. A step-down multiple regression method was
      used to identify important contributing factors. RESULTS: Factors that increased
      extrication times by a statistically significant extent were: a physical
      obstruction (10 min), patients medically trapped (10 min per patient) and any
      patient physically trapped (7 min). Factors that shortened extrication time were
      rapid access (-7 min) and the car being on its roof (-12 min). All these times
      were calculated from an arbitrary time (which assumes zero patients) of 8 min.
      CONCLUSIONS: This paper describes the development of a tool to predict
      extrication time for a trapped patient. A number of factors were identified which
      significantly contributed to the overall extrication time.

PMID- 24743588
TI  - Parallel imaging-based reduction of acoustic noise for clinical magnetic
      resonance imaging.
AB  - OBJECTIVES: The objective of this study was to demonstrate the feasibility of
      improving perceived acoustic comfort for a standard clinical magnetic resonance
      imaging protocol via gradient wave form optimization and validate parallel
      imaging as a means to achieve a further reduction of acoustic noise. MATERIALS
      AND METHODS: The gradient wave forms of a standard T2 axial turbo spin-echo (TSE)
      sequence in head examinations were modified for acoustic performance while
      attempting to keep the total acquisition and inter-echo spacing the same.
      Parallel imaging was then used to double the inter-echo spacing and allow further
      wave form optimization. Along with comparative acoustic noise measurements, a
      statistical analysis of radiologist scoring was conducted on volumes from
      standard and modified sequences acquired from 10 patients after informed consent
      was obtained. RESULTS: Compared with TSE, significant improvement of acoustic
      comfort was measured for modified-sequences quiet TSE and quiet TSE with
      generalized autocalibrating partially parallel acquisitions (P = 0.0034 and P =
      0.0003, respectively), and no statistically significant difference in diagnostic
      quality was observed without the use of parallel imaging. CONCLUSIONS: Standard
      clinical magnetic resonance imaging protocols can be made quieter through
      adequate gradient wave form optimization. In scans with high signal-to-noise
      ratio, parallel imaging can be used to further reduce acoustic noise.

PMID- 24743590
TI  - Phylodynamic inference for structured epidemiological models.
AB  - Coalescent theory is routinely used to estimate past population dynamics and
      demographic parameters from genealogies. While early work in coalescent theory
      only considered simple demographic models, advances in theory have allowed for
      increasingly complex demographic scenarios to be considered. The success of this
      approach has lead to coalescent-based inference methods being applied to
      populations with rapidly changing population dynamics, including pathogens like
      RNA viruses. However, fitting epidemiological models to genealogies via
      coalescent models remains a challenging task, because pathogen populations often
      exhibit complex, nonlinear dynamics and are structured by multiple factors.
      Moreover, it often becomes necessary to consider stochastic variation in
      population dynamics when fitting such complex models to real data. Using recently
      developed structured coalescent models that accommodate complex population
      dynamics and population structure, we develop a statistical framework for fitting
      stochastic epidemiological models to genealogies. By combining particle filtering
      methods with Bayesian Markov chain Monte Carlo methods, we are able to fit a wide
      class of stochastic, nonlinear epidemiological models with different forms of
      population structure to genealogies. We demonstrate our framework using two
      structured epidemiological models: a model with disease progression between
      multiple stages of infection and a two-population model reflecting spatial
      structure. We apply the multi-stage model to HIV genealogies and show that the
      proposed method can be used to estimate the stage-specific transmission rates and
      prevalence of HIV. Finally, using the two-population model we explore how much
      information about population structure is contained in genealogies and what
      sample sizes are necessary to reliably infer parameters like migration rates. 

PMID- 24743589
TI  - Assessment of renal artery stenosis using intravoxel incoherent motion diffusion
      weighted magnetic resonance imaging analysis.
AB  - OBJECTIVES: Diffusion-weighted magnetic resonance imaging is a powerful tool to
      assess renal morphology. However, its quantitative index, apparent diffusion
      coefficient (ADC), derived from a conventional monoexponential model can vary
      with both functional and structural alterations as well as the choice of b
      values. In contrast, the intravoxel incoherent motion (IVIM) biexponential model
      provides independent parameters that may represent broader aspects of renal
      pathophysiology. We hypothesized that IVIM analysis is capable of detecting early
      morphological and functional changes in the swine kidney distal to renal artery
      stenosis (RAS). MATERIALS AND METHODS: Domestic pigs divided into 3 groups (n = 6
      7 each) were studied for 16 weeks. Unilateral RAS was induced in 2 groups, of
      which 1 group was fed with a high-cholesterol diet to induce early
      atherosclerosis (ARAS), whereas the other (RAS) consumed regular diet. The third
      group included healthy pigs that served as control sham. Renal function,
      hemodynamics, tubular function, and morphology were assessed using multidetector
      computed tomography and histology. Diffusion-weighted magnetic resonance images
      were acquired at 3T and analyzed using monoexponential and biexponential models.
      Parameters of ADC and IVIM (diffusivity [D(t)], flow-dependent pseudodiffusivity
      [D(p)], and fluid fraction [f(p)]) were calculated in the cortex and medulla of
      the stenotic (STK) and contralateral kidneys (CLKs). Results were analyzed using
      analysis of variance, Student t test, and regression analysis. RESULTS: In both
      RAS and ARAS, the STK shrank and the CLK underwent hypertrophy. Glomerular
      filtration rate and renal blood flow declined in STKs, and CLKs manifested
      hyperfiltration. In addition, ARAS kidneys showed reduced mean transit time in
      distal tubular segments. Apparent diffusion coefficient and diffusivity both
      decreased in STK of RAS and ARAS. D(p) and f(p) were elevated in both the STK and
      CLK of RAS and more prominently in ARAS. The STK cortical ADC and D(t) correlated
      inversely with the degree of fibrosis and directly with glomerular filtration
      rate. Furthermore, D(p) correlated with tubular injury score in all kidneys.
      CONCLUSIONS: Apparent diffusion constant and D(t) both correlated with cortical
      and medullary fibrosis; however, IVIM-derived parameters can detect subtle
      functional and structural changes in the post-STK and may also serve as markers
      for tubular injury.

PMID- 24743591
TI  - Sphingosine kinase 1 expressed by endothelial colony-forming cells has a critical
      role in their revascularization activity.
AB  - AIMS: Cell therapy based on endothelial colony-forming cells (ECFCs) is a
      promising option for ischaemic cardiovascular diseases. A better understanding of
      the mechanisms by which these cells promote revascularization remains a critical
      challenge to improving their therapeutic potential. We aimed to identify the
      critical mechanisms involved in the revascularization activity of ECFCs by using
      the paracrine properties of mesenchymal stem cells (MSC). METHODS AND RESULTS:
      Conditioned medium from human bone marrow-derived MSCs (MSC-CM) increased the
      angiogenic activity of cord blood ECFCs in vitro (proliferation, migration, and
      pseudo-tube formation), the survival of ECFCs in mice (Matrigel Plug assay), and
      the capacity of ECFCs to promote the recovery of blood perfusion in mice with
      hindlimb ischaemia. Furthermore, the capillary density in ischaemic gastrocnemius
      muscle was significantly increased in mice transplanted with the ECFCs pre
      treated with the MSC-CM. The enhancement of ECFCs activity involved the up
      regulation of sphingosine kinase 1 (SphK1) expression and activity. The
      inhibition of SphK1 in ECFCs by using an inhibitor or a siRNA knockdown of SphK1
      prevented the stimulation of the ECFCs induced by the MSC-CM. The improvement of
      ECFC activity by MSC-CM also involved the up-regulation of sphingosine-1
      phosphate receptor 1 (S1P1) and a S1P/S1P1/3-dependent mechanism. Finally, we
      showed that the stimulation of ECFCs with exogenous S1P increased angiogenesis
      and promoted blood perfusion in hindlimb ischaemia. CONCLUSION: The up-regulation
      of SphK1 and S1P-dependent pathways is critical for the angiogenic/vasculogenic
      activity of ECFCs. The identification of this pathway provides attractive targets
      to optimize cell-based therapy for revascularization in ischaemic diseases.

PMID- 24743593
TI  - Intramuscular fat accumulation and muscle atrophy in the absence of muscle
      retraction.
AB  - OBJECTIVES: Although many clinical and experimental investigations have shed
      light on muscle atrophy and intramuscular accumulation of fat after rotator cuff
      disruption, none have reported on their onset in the absence of muscle
      retraction. METHODS: In 30 rabbits, we detached one supraspinatus (SSP) tendon
      and repaired it immediately, thus preventing muscle retraction. The animals were
      killed in groups of 10 at one, two and six weeks. Both shoulders of 15 non
      operated rabbits served as controls. We measured the weight and volume of SSP
      muscles and quantified the cross-sectional area of intramuscular fat (i-fat)
      histologically. RESULTS: There was significant loss of muscle weight and volume
      after one week (p = 0.004 and 0.003, respectively), and two weeks (both p <
      0.001) in the experimental group; which recovered to control values after six
      weeks. I-fat accumulated one week after immediate repair, greater than in the
      control group and statistically significant at the mid-part of the muscle (mean
      2.7% vs 1.5%, p = 0.008). I-fat continued to accumulate up to six weeks at all
      sites of the SSP muscle (all 3, p < 0.001). More fat accumulated closer to the
      musculotendinous junction than at the mid-part after two and six weeks (p = 0.012
      and 0.019, respectively). CONCLUSION: Muscle atrophy and i-fat accumulation occur
      early after SSP tendon tear and immediate repair. While early repair benefitted
      muscle recovery, it did not prevent fat accumulation. SSP muscle retraction was
      not essential to the muscle alterations. The divergent evolution of muscle and
      fat points to different pathophysiologies. Cite this article: Bone Joint Res
      2014;3:117-22.

PMID- 24743592
TI  - Muscle-derived follistatin-like 1 functions to reduce neointimal formation after
      vascular injury.
AB  - AIMS: It is well-established that exercise diminishes cardiovascular risk, but
      whether humoral factors secreted by muscle confer these benefits has not been
      conclusively shown. We have shown that the secreted protein follistatin-like 1
      (Fstl1) has beneficial actions on cardiac and endothelial function. However, the
      role of muscle-derived Fstl1 in proliferative vascular disease remains largely
      unknown. Here, we investigated whether muscle-derived Fstl1 modulates vascular
      remodelling in response to injury. METHODS AND RESULTS: The targeted ablation of
      Fstl1 in muscle led to an increase in neointimal formation following wire-induced
      arterial injury compared with control mice. Conversely, muscle-specific Fstl1
      transgenic (TG) mice displayed a decrease in the neointimal thickening following
      arterial injury. Muscle-specific Fstl1 ablation and overexpression increased and
      decreased, respectively, the frequency of BrdU-positive proliferating cells in
      injured vessels. In cultured human aortic smooth muscle cells (HASMCs), treatment
      with human FSTL1 protein decreased proliferation and migration induced by
      stimulation with PDGF-BB. Treatment with FSTL1 enhanced AMPK phosphorylation, and
      inhibition of AMPK abrogated the inhibitory actions of FSTL1 on HASMC responses
      to PDGF-BB. The injured arteries of Fstl1-TG mice exhibited an increase in AMPK
      phosphorylation, and administration of AMPK inhibitor reversed the anti
      proliferative actions of Fstl1 on the vessel wall. CONCLUSION: Our findings
      indicate that muscle-derived Fstl1 attenuates neointimal formation in response to
      arterial injury by suppressing SMC proliferation through an AMPK-dependent
      mechanism. Thus, the release of protein factors from muscle, such as Fstl1, may
      partly explain why the maintenance of muscle function can have a therapeutic
      effect on the cardiovascular system.

PMID- 24743594
TI  - Autoregulation of the 26S proteasome by in situ ubiquitination.
AB  - The 26S proteasome degrades ubiquitinated proteins, and proteasomal degradation
      controls various cellular events. Here we report that the human 26S proteasome is
      ubiquitinated, by which the ubiquitin receptors Adrm1 and S5a, the ATPase subunit
      Rpt5, and the deubiquitinating enzyme Uch37 are ubiquitinated in situ by
      proteasome-associating ubiquitination enzymes. Ubiquitination of these subunits
      significantly impairs the 26S proteasome's ability to bind, deubiquitinate, and
      degrade ubiquitinated proteins. Moreover, ubiquitination of the 26S proteasome
      can be antagonized by proteasome-residing deubiquitinating enzymes, by the
      binding of polyubiquitin chains, and by certain cellular stress, indicating that
      proteasome ubiquitination is dynamic and regulated in cells. We propose that in
      situ ubiquitination of the 26S proteasome regulates its activity, which could
      function to adjust proteasomal activity in response to the alteration of cellular
      ubiquitination levels.

PMID- 24743595
TI  - Cytoplasmic carboxypeptidase 5 regulates tubulin glutamylation and zebrafish
      cilia formation and function.
AB  - Glutamylation is a functionally important tubulin posttranslational modification
      enriched on stable microtubules of neuronal axons, mitotic spindles, centrioles,
      and cilia. In vertebrates, balanced activities of tubulin glutamyl ligase and
      cytoplasmic carboxypeptidase deglutamylase enzymes maintain organelle- and cell
      type-specific tubulin glutamylation patterns. Tubulin glutamylation in cilia is
      regulated via restricted subcellular localization or expression of tubulin
      glutamyl ligases (ttlls) and nonenzymatic proteins, including the zebrafish TPR
      repeat protein Fleer/Ift70. Here we analyze the expression patterns of ccp
      deglutamylase genes during zebrafish development and the effects of ccp gene
      knockdown on cilia formation, morphology, and tubulin glutamylation. The
      deglutamylases ccp2, ccp5, and ccp6 are expressed in ciliated cells, whereas ccp1
      expression is restricted to the nervous system. Only ccp5 knockdown increases
      cilia tubulin glutamylation, induces ciliopathy phenotypes, including axis
      curvature, hydrocephalus, and pronephric cysts, and disrupts multicilia motility,
      suggesting that Ccp5 is the principal tubulin deglutamylase that maintains
      functional levels of cilia tubulin glutamylation. The ability of ccp5 knockdown
      to restore cilia tubulin glutamylation in fleer/ift70 mutants and rescue
      pronephric multicilia formation in both fleer- and ift88-deficient zebrafish
      indicates that tubulin glutamylation is a key driver of ciliogenesis.

PMID- 24743596
TI  - Cooperative endocytosis of the endosomal SNARE protein syntaxin-8 and the
      potassium channel TASK-1.
AB  - The endosomal SNARE protein syntaxin-8 interacts with the acid-sensitive
      potassium channel TASK-1. The functional relevance of this interaction was
      studied by heterologous expression of these proteins (and mutants thereof) in
      Xenopus oocytes and in mammalian cell lines. Coexpression of syntaxin-8 caused a
      fourfold reduction in TASK-1 current, a corresponding reduction in the expression
      of TASK-1 at the cell surface, and a marked increase in the rate of endocytosis
      of the channel. TASK-1 and syntaxin-8 colocalized in the early endosomal
      compartment, as indicated by the endosomal markers 2xFYVE and rab5. The
      stimulatory effect of the SNARE protein on the endocytosis of the channel was
      abolished when both an endocytosis signal in TASK-1 and an endocytosis signal in
      syntaxin-8 were mutated. A syntaxin-8 mutant that cannot assemble with other
      SNARE proteins had virtually the same effect as wild-type syntaxin-8. Total
      internal reflection fluorescence microscopy showed formation and endocytosis of
      vesicles containing fluorescence-tagged clathrin, TASK-1, and/or syntaxin-8. Our
      results suggest that the unassembled form of syntaxin-8 and the potassium channel
      TASK-1 are internalized via clathrin-mediated endocytosis in a cooperative
      manner. This implies that syntaxin-8 regulates the endocytosis of TASK-1. Our
      study supports the idea that endosomal SNARE proteins can have functions
      unrelated to membrane fusion.

PMID- 24743597
TI  - The adaptor protein GULP promotes Jedi-1-mediated phagocytosis through a clathrin
      dependent mechanism.
AB  - During the development of the peripheral nervous system, the large number of
      apoptotic neurons generated are phagocytosed by glial precursor cells. This
      clearance is mediated, in part, through the mammalian engulfment receptor Jedi-1.
      However, the mechanisms by which Jedi-1 mediates phagocytosis are poorly
      understood. Here we demonstrate that Jedi-1 associates with GULP, the mammalian
      homologue of CED-6, an adaptor protein required for phagocytosis mediated by the
      nematode engulfment receptor CED-1. Silencing GULP or mutating the NPXY motif in
      Jedi-1, which is required for GULP binding, prevents Jedi-1-mediated
      phagocytosis. How GULP promotes engulfment is not known. Of interest, we find
      that Jedi-1-induced phagocytosis requires GULP binding to clathrin heavy chain
      (CHC). During engulfment, CHC is tyrosine phosphorylated, which is required for
      Jedi-mediated engulfment. Both phosphoclathrin and actin accumulate around
      engulfed microspheres. Furthermore, knockdown of CHC in HeLa cells prevents Jedi
      1-mediated engulfment of microspheres, and knockdown in glial precursors prevents
      the engulfment of apoptotic neurons. Taken together, these results reveal that
      Jedi-1 signals through recruitment of GULP, which promotes phagocytosis through a
      noncanonical phosphoclathrin-dependent mechanism.

PMID- 24743598
TI  - Alpha-tubulin K40 acetylation is required for contact inhibition of proliferation
      and cell-substrate adhesion.
AB  - Acetylation of alpha-tubulin on lysine 40 marks long-lived microtubules in
      structures such as axons and cilia, and yet the physiological role of alpha
      tubulin K40 acetylation is elusive. Although genetic ablation of the alpha
      tubulin K40 acetyltransferase alphaTat1 in mice did not lead to detectable
      phenotypes in the developing animals, contact inhibition of proliferation and
      cell-substrate adhesion were significantly compromised in cultured alphaTat1(-/-)
      fibroblasts. First, alphaTat1(-/-) fibroblasts kept proliferating beyond the
      confluent monolayer stage. Congruently, alphaTat1(-/-) cells failed to activate
      Hippo signaling in response to increased cell density, and the microtubule
      association of the Hippo regulator Merlin was disrupted. Second, alphaTat1(-/-)
      cells contained very few focal adhesions, and their ability to adhere to growth
      surfaces was greatly impaired. Whereas the catalytic activity of alphaTAT1 was
      dispensable for monolayer formation, it was necessary for cell adhesion and
      restrained cell proliferation and activation of the Hippo pathway at elevated
      cell density. Because alpha-tubulin K40 acetylation is largely eliminated by
      deletion of alphaTAT1, we propose that acetylated microtubules regulate contact
      inhibition of proliferation through the Hippo pathway.

PMID- 24743599
TI  - Identification of restriction-modification systems of Bifidobacterium animalis
      subsp. lactis CNCM I-2494 by SMRT sequencing and associated methylome analysis.
AB  - Bifidobacterium animalis subsp. lactis CNCM I-2494 is a component of a
      commercialized fermented dairy product for which beneficial effects on health has
      been studied by clinical and preclinical trials. To date little is known about
      the molecular mechanisms that could explain the beneficial effects that
      bifidobacteria impart to the host. Restriction-modification (R-M) systems have
      been identified as key obstacles in the genetic accessibility of bifidobacteria,
      and circumventing these is a prerequisite to attaining a fundamental
      understanding of bifidobacterial attributes, including the genes that are
      responsible for health-promoting properties of this clinically and industrially
      important group of bacteria. The complete genome sequence of B. animalis subsp.
      lactis CNCM I-2494 is predicted to harbour the genetic determinants for two type
      II R-M systems, designated BanLI and BanLII. In order to investigate the
      functionality and specificity of these two putative R-M systems in B. animalis
      subsp. lactis CNCM I-2494, we employed PacBio SMRT sequencing with associated
      methylome analysis. In addition, the contribution of the identified R-M systems
      to the genetic accessibility of this strain was assessed. 

PMID- 24743602
TI  - Coregulation in Romantic Partners' Attachment Styles: A Longitudinal
      Investigation.
AB  - The goal of the present research was to examine the coregulation of partner
      specific attachment security in romantic relationships. We studied a sample of
      172 couples 5 times over 1 year. At each assessment wave, partners independently
      completed a self-report measure of their security in the relationship. We
      operationalized attachment coregulation both as direct impacts (i.e., prospective
      effects of one partner on the other) and coordination (i.e., correlated changes
      across time). Results indicated that, after taking into account people's
      prototypical levels of security, changes in security were coordinated within
      couples.

PMID- 24743600
TI  - Genetic control of differential acetylation in diabetic rats.
AB  - Post-translational protein modifications such as acetylation have significant
      regulatory roles in metabolic processes, but their relationship to both variation
      in gene expression and DNA sequence is unclear. We address this question in the
      Goto-Kakizaki (GK) rat inbred strain, a model of polygenic type 2 diabetes.
      Expression of the NAD-dependent deacetylase Sirtuin-3 is down-regulated in GK
      rats compared to normoglycemic Brown Norway (BN) rats. We show first that a
      promoter SNP causes down-regulation of Sirtuin-3 expression in GK rats. We then
      use mass-spectrometry to identify proteome-wide differential lysine acetylation
      of putative Sirtuin-3 protein targets in livers of GK and BN rats. These include
      many proteins in pathways connected to diabetes and metabolic syndrome. We
      finally sequence GK and BN liver transcriptomes and find that mRNA expression of
      these targets does not differ significantly between GK and BN rats, in contrast
      to other components of the same pathways. We conclude that physiological
      differences between GK and BN rats are mediated by a combination of differential
      protein acetylation and gene transcription and that genetic variation can
      modulate acetylation independently of expression. 

PMID- 24743601
TI  - Downregulation of 14-3-3sigma correlates with multistage carcinogenesis and poor
      prognosis of esophageal squamous cell carcinoma.
AB  - AIMS: The asymptomatic nature of early-stage esophageal squamous cell carcinoma
      (ESCC) results in late presentation and consequent dismal prognosis This study
      characterized 14-3-3sigma protein expression in the multi-stage development of
      ESCC and determined its correlation with clinical features and prognosis.
      MATERIALS AND METHODS: Western blot was used to examine 14-3-3sigma protein
      expression in normal esophageal epithelium (NEE), low grade intraepithelial
      neoplasia (LGIN), high grade intraepithelial neoplasia (HGIN), ESCC of TNM I to
      IV stage and various esophageal epithelial cell lines with different biological
      behavior. Immunohistochemistry was used to estimate 14-3-3sigma protein in 110
      biopsy samples of NEE, LGIN or HGIN and in 168 ESCC samples all of whom had
      follow-up data. Support vector machine (SVM) was used to develop a classifier for
      prognosis. RESULTS: 14-3-3sigma decreased progressively from NEE to LGIN, to
      HGIN, and to ESCC. Chemoresistant sub-lines of EC9706/PTX and EC9706/CDDP showed
      high expression of 14-3-3sigma protein compared with non-chemoresistant ESCC cell
      lines and immortalized NEC. Furthermore, the downregulation of 14-3-3sigma
      correlated significantly with histological grade (P = 0.000) and worse prognosis
      (P = 0.004). Multivariate Cox regression analysis indicated that 14-3-3sigma
      protein (P = 0.016) and T stage (P = 0.000) were independent prognostic factors
      for ESCC. The SVM ESCC classifier comprising sex, age, T stage, histological
      grade, lymph node metastasis, clinical stage and 14-3-3sigma, distinguished
      significantly lower- and higher-risk ESCC patients (91.67% vs. 3.62%, P = 0.000).
      CONCLUSIONS: Downregulation of 14-3-3sigma arises early in the development of
      ESCC and predicts poor survival, suggesting that 14-3-3sigma may be a biomarker
      for early detection of high-risk subjects and diagnosis of ESCC. Our seven
      feature SVM classifier for ESCC prognosis may help to inform clinical decisions
      and tailor individual therapy.

PMID- 24743603
TI  - Self-Interest Bias in Moral Judgments of Others' Actions.
AB  - The automatic and affective nature of moral judgments leads to the expectation
      that these judgments are biased by an observer's own interests. Although the idea
      of self-interest bias is old, it has never been directly tested with respect to
      the moral judgments of other individuals' behaviors. The participants of three
      experiments observed other individuals' counternormative behavior (breaking a
      rule or cheating for gain), which was judged as immoral. However, this judgment
      became much more lenient when the observers gained from the observed behavior.
      All three studies showed that the influence of self-interest on moral judgments
      was completely mediated by the observer's increased liking for the perpetrator of
      the immoral acts but not by changes in mood. When the participants were induced
      to dislike the perpetrator (in a moderation-of-process design), the self-interest
      bias disappeared. Implications for the intuitionist approach to moral judgment
      are discussed.

PMID- 24743605
TI  - Reply to letter: "pancreatic fistula after pancreaticoduodenectomy".

PMID- 24743604
TI  - Variation in hospital mortality rates with inpatient cancer surgery.
AB  - OBJECTIVE: To elucidate clinical mechanisms underlying variation in hospital
      mortality after cancer surgery BACKGROUND: : Thousands of Americans die every
      year undergoing elective cancer surgery. Wide variation in hospital mortality
      rates suggest opportunities for improvement, but these efforts are limited by
      uncertainty about why some hospitals have poorer outcomes than others. METHODS:
      Using data from the 2006-2007 National Cancer Data Base, we ranked 1279 hospitals
      according to a composite measure of perioperative mortality after operations for
      bladder, esophagus, colon, lung, pancreas, and stomach cancers. We then conducted
      detailed medical record review of 5632 patients at 1 of 19 hospitals with low
      mortality rates (2.1%) or 30 hospitals with high mortality rates (9.1%).
      Hierarchical logistic regression analyses were used to compare risk-adjusted
      complication incidence and case-fatality rates among patients experiencing
      serious complications. RESULTS: The 7.0% absolute mortality difference between
      the 2 hospital groups could be attributed to higher mortality from surgical site,
      pulmonary, thromboembolic, and other complications. The overall incidence of
      complications was not different between hospital groups [21.2% vs 17.8%; adjusted
      odds ratio (OR) = 1.34, 95% confidence interval (CI): 0.93-1.94]. In contrast,
      case-fatality after complications was more than threefold higher at high
      mortality hospitals than at low mortality hospitals (25.9% vs 13.6%; adjusted OR
      = 3.23, 95% CI: 1.56-6.69). CONCLUSIONS: Low mortality and high mortality
      hospitals are distinguished less by their complication rates than by how
      frequently patients die after a complication. Strategies for ensuring the timely
      recognition and effective management of postoperative complications will be
      essential in reducing mortality after cancer surgery.

PMID- 24743606
TI  - Derivation and validation of a quality indicator of acute care length of stay to
      evaluate trauma care.
AB  - OBJECTIVE: To derive and internally validate a quality indicator (QI) for acute
      care length of stay (LOS) after admission for injury. BACKGROUND: Unnecessary
      hospital days represent an estimated 20% of total LOS implying an important waste
      of resources as well as increased patient exposure to hospital-acquired
      infections and functional decline. METHODS: This study is based on a multicenter,
      retrospective cohort from a Canadian provincial trauma system (2005-2010; 57
      trauma centers; n = 57,524). Data were abstracted from the provincial trauma
      registry and the hospital discharge database. Candidate risk factors were
      identified by expert consensus and selected for model derivation using bootstrap
      resampling. The validity of the QI was evaluated in terms of interhospital
      discrimination, construct validity, and forecasting. RESULTS: The risk adjustment
      model explains 37% of the variation in LOS. The QI discriminates well across
      trauma centers (coefficient of variation = 0.02, 95% confidence interval: 0.011
      0.028) and is correlated with the QI on processes of care (r = -0.32),
      complications (r = 0.66), unplanned readmissions (r = 0.38), and mortality (r =
      0.35). Performance in 2005 to 2007 was predictive of performance in 2008 to 2010
      (r = 0.80). CONCLUSIONS: We have developed a QI on the basis of risk-adjusted LOS
      to evaluate trauma care that can be implemented with routinely collected data.
      The QI is based on a robust risk adjustment model with good internal and temporal
      validity, and demonstrates good properties in terms of discrimination, construct
      validity, and forecasting. This QI can be used to target interventions to reduce
      LOS, which will lead to more efficient resource use and may improve patient
      outcomes after injury.

PMID- 24743607
TI  - Marking axillary lymph nodes with radioactive iodine seeds for axillary staging
      after neoadjuvant systemic treatment in breast cancer patients: the MARI
      procedure.
AB  - OBJECTIVE: The MARI procedure [marking the axillary lymph node with radioactive
      iodine (I) seeds] is a new minimal invasive method to assess the pathological
      response of nodal metastases after neoadjuvant systemic treatment (NST) in
      patients with breast cancer. This method allows axilla-conserving surgery in
      patients responding well to NST. METHODS: Prior to NST, proven tumor-positive
      axillary lymph nodes were marked with a I seed. This marked lymph node is the so
      called MARI-node. After NST, the MARI node was selectively removed using a gamma
      detection probe. A complementary axillary lymph node dissection was performed in
      all patients to assess whether pathological response in the MARI node was
      indicative for the pathological response in the additional lymph nodes. RESULTS:
      A tumor-positive axillary lymph node was marked with a I seed in 100 patients.
      The MARI node was successfully identified in 97 of these 100 patients
      (identification rate 97%). Two patients did not undergo subsequent axillary lymph
      node dissection, leaving 95 patients for further analysis. The MARI node
      contained residual tumor cells in 65 of these 95 patients. In the other 30
      patients, the MARI node was free of tumor, but additional positive lymph nodes
      were found in 5 patients. Thus, the MARI procedure correctly identified 65 of 70
      patients with residual axillary tumor activity (false negative rate 5/70 = 7%).
      CONCLUSIONS: This study shows that marking and selectively removing metastatic
      lymph nodes after neoadjuvant systemic treatment has a high identification rate
      and a low false negative rate. The tumor response in the marked lymph node may be
      used to tailor further axillary treatment after NST.

PMID- 24743608
TI  - Increasing access to specialty surgical care: application of a new resource
      allocation model to bariatric surgery.
AB  - OBJECTIVES: To calculate the public health impact and economic benefit of using
      ancillary health care professionals for routine postoperative care. BACKGROUND:
      The need for specialty surgical care far exceeds its supply, particularly in
      weight loss surgery. Bariatric surgery is cost-effective and the only effective
      long-term weight loss strategy for morbidly obese patients. Without clinically
      appropriate task shifting, surgeons, hospitals, and untreated patients incur a
      high opportunity cost. METHODS: Visit schedules, time per visit, and revenues
      were obtained from bariatric centers of excellence. Case-specific surgeon fees
      were derived from published Current Procedural Terminology data. The novel
      Microsoft Excel model was allowed to run until a steady state was evident (status
      quo). This model was compared with one in which the surgeon participates in
      follow-up visits beyond 3 months only if there is a complication (task shifting).
      Changes in operative capacity and national quality-adjusted life years (QALYs)
      were calculated. RESULTS: In the status quo model, per capita surgical volume
      capacity equilibrates at 7 surgical procedures per week, with 27% of the
      surgeon's time dedicated to routine long-term follow-up visits. Task shifting
      increases operative capacity by 38%, resulting in 143,000 to 882,000 QALYs gained
      annually. Per surgeon, task shifting achieves an annual increase of 95 to 588
      QALYs, $5 million in facility revenue, 48 cases of cure of obstructive sleep
      apnea, 44 cases of remission of type 2 diabetes mellitus, and 35 cases of cure of
      hypertension. CONCLUSIONS: Optimal resource allocation through task shifting is
      economically appealing and can achieve dramatic public health benefit by
      increasing access to specialty surgery.

PMID- 24743609
TI  - A risk model for esophagectomy using data of 5354 patients included in a Japanese
      nationwide web-based database.
AB  - OBJECTIVE: This study aimed to create a risk model of mortality associated with
      esophagectomy using a Japanese nationwide database. METHODS: A total of 5354
      patients who underwent esophagectomy in 713 hospitals in 2011 were evaluated.
      Variables and definitions were virtually identical to those adopted by the
      American College of Surgeons National Surgical Quality Improvement Program.
      RESULTS: The mean patient age was 65.9 years, and 84.3% patients were male. The
      overall morbidity rate was 41.9%. Thirty-day and operative mortality rates after
      esophagectomy were 1.2% and 3.4%, respectively. Overall morbidity was
      significantly higher in the minimally invasive esophagectomy group than in the
      open esophagectomy group (44.3% vs 40.8%, P = 0.016). The odds ratios for 30-day
      mortality in patients who required preoperative assistance in activities of daily
      living (ADL), those with a history of smoking within 1 year before surgery, and
      those with weight loss more than 10% within 6 months before surgery were 4.2,
      2.6, and 2.4, respectively. The odds ratios for operative mortality in patients
      who required preoperative assistance in ADL, those with metastasis/relapse, male
      patients, and those with chronic obstructive pulmonary disease were 4.7, 4.5,
      2.3, and 2.1, respectively. CONCLUSIONS: This study was the first, as per our
      knowledge, to perform risk stratification for esophagectomy using a Japanese
      nationwide database. The 30-day and operative mortality rates were relatively
      lower than those in previous reports. The risk models developed in this study may
      contribute toward improvements in quality control of procedures and creation of a
      novel scoring system.

PMID- 24743611
TI  - Evidence for preoperative aspirin improving major outcomes in patients with
      chronic kidney disease undergoing cardiac surgery: a cohort study.
AB  - BACKGROUND: Effects of aspirin on patients with chronic kidney disease (CKD)
      remains unclear. This study aimed to examine the effect of preoperative aspirin
      use on postoperative renal function and 30-day mortality in patients with CKD
      undergoing cardiac surgery. METHODS: A retrospective cohort study was performed
      on consecutive patients (n = 5175) receiving cardiac surgery in 2 tertiary
      hospitals. Of all patients, 3585 met the inclusion criteria and underwent the
      analysis to determine the association of preoperative aspirin with incidence of
      acute kidney injury (AKI) and death based on estimated glomerular filtration rate
      (eGFR). RESULTS: Of 3585 patients, 31.5% had CKD (eGFR < 60 mL/min/1.73 m2) at
      baseline and 27.6% had AKI postoperatively. The baseline eGFR had a nonlinear
      relationship with the incidence and stages of AKI. As eGFR decreased to 15 to 30
      from more than or equal to 90 mL/min/1.73 m2, AKI and 30-day mortality increased
      to 50.5% from 23.5% and to 11.9% from 2.6%, respectively (P < 0.001). However,
      preoperative aspirin use was associated with a significant decrease in
      postoperative AKI and 30-day mortality in patients with CKD undergoing cardiac
      surgery, in particular, the survival benefit associated with aspirin was greater
      in patients with CKD (vs normal kidney function): 30-day mortality was reduced by
      23.3%, 58.2%, or 70.0% for patients with baseline eGFR more than or equal to 90,
      30 to 59, or 15 to 30 mL/min/1.73 m2, respectively (P trend < 0.001).
      CONCLUSIONS: For patients with CKD undergoing cardiac surgery, preoperative
      aspirin therapy was associated with renal protection and mortality decline. The
      magnitude of the survival benefit was greater in patients with CKD than normal
      kidney function.

PMID- 24743610
TI  - The effect of renin angiotensin system genetic variants in acute pancreatitis.
AB  - OBJECTIVES: We sought association of genetic variants in the renin-angiotensin
      system (RAS) and vitamin D system with acute pancreatitis (AP) development and
      severity. BACKGROUND: The endocrine RAS is involved in circulatory homeostasis
      through the pressor action of angiotensin II at its AT1 receptor. However, local
      RAS regulate growth and inflammation in diverse cells and tissues, and their
      activity may be suppressed by vitamin D. Intrapancreatic angiotensin II
      generation has been implicated in the development of AP. METHODS: Five hundred
      forty-four white patients with AP from 3 countries (United Kingdom, 22; Germany,
      136; and The Netherlands 386) and 8487 control subjects (United Kingdom 7833, The
      Netherlands 717) were genotyped for 8 polymorphisms of the RAS/vitamin D systems,
      chosen on the basis of likely functionality. RESULTS: The angiotensin-converting
      enzyme I (rather than D) allele was significantly associated with alcohol-related
      AP when all cohorts were combined (P = 0.03). The renin rs5707 G (rather than A)
      allele was associated with AP (P = 0.002), infected necrosis (P = 0.025) and
      mortality (P = 0.046). CONCLUSIONS: The association of 2 RAS polymorphisms with
      AP suggests the need for further detailed analysis of the role of RAS/vitamin D
      in the genesis or severity of AP, particularly given the ready potential for
      pharmacological manipulation of this system using existing marketed agents.
      However, further replication studies will be required before any such association
      is considered robust, particularly given the significant heterogeneity of AP
      causation and clinical course.

PMID- 24743612
TI  - Barrett's esophagus and antireflux surgery: wraps, rings, and HALOs.

PMID- 24743613
TI  - Single incision laparoscopic cholecystectomy is associated with a higher bile
      duct injury rate: a review and word of caution.

PMID- 24743614
TI  - Reoperation versus clinical recurrence rate after ventral hernia repair.

PMID- 24743615
TI  - Postoperative transitional care needs in the elderly: an outcome of recovery
      associated with worse long-term survival.
AB  - OBJECTIVE: To characterize transitional care needs (TCNs) after colorectal cancer
      (CRC) surgery and examine their association with age and impact on overall
      survival (OS). BACKGROUND: TCNs after cancer surgery represent additional burden
      for patients and are associated with higher short-term mortality. They are not
      well-characterized in CRC patients, particularly in the context of a growing
      elderly population, and their effect on long-term survival is unknown. METHODS: A
      retrospective cohort study of CRC patients (N = 486) having curative surgery at a
      tertiary referral center (2002-2011) was conducted. Outcomes included TCNs (home
      health or nonhome destination at discharge) and OS. Patients were compared on the
      basis of age: young (<65 years), old (65-74 years), and oldest (>=75 years).
      Multivariate logistic regression models were used to examine the association of
      age with TCNs, and OS was compared on the basis of TCNs and stage, using the
      Kaplan-Meier method. RESULTS: TCNs were required by 130 patients (27%). The
      oldest patients had highest TCNs (49%) compared with the other age groups (P <
      0.01), with rehabilitation services as their primary TCNs (80%). After
      multivariate analysis, patients 75 years or older had significantly increased TCN
      risk (odds ratio, 4.7; 95% confidence interval, 2.6-8.5). TCN was associated with
      worse OS for patients with early- and advanced stage CRC (P < 0.001).
      CONCLUSIONS: TCNs after CRC surgery are common and significantly increased in
      patients 75 years or older, represent an outcome of postoperative recovery, and
      are associated with worse long-term survival. Preoperative identification of
      higher risk populations should be used for patient counseling, advanced
      preoperative planning, and to implement strategies targeted at minimizing TCNs.

PMID- 24743616
TI  - Reply to letter: "surgical education research: an IDEAL proposition".

PMID- 24743617
TI  - Reply to Letter: "Residual Esophageal Cancer After Neoadjuvant Chemoradiotherapy
      Frequently Involves the Mucosa and Submucosa".

PMID- 24743618
TI  - Reply to Letter: "Effect of Simvastatin on Physiological and Biological Outcomes
      in Patients Undergoing Esophagectomy: A Randomized Placebo-controlled Trial".

PMID- 24743619
TI  - Residual Esophageal Cancer After Neoadjuvant Chemoradiotherapy Frequently
      Involves the Mucosa and Submucosa.

PMID- 24743620
TI  - The Role of Surgery in Patients With a Complete Clinical Response After
      Chemoradiation for Esophageal Cancer.

PMID- 24743621
TI  - Surgical education research: an IDEAL proposition.

PMID- 24743622
TI  - Predicting recurrence of pancreatic solid pseudopapillary tumors after surgical
      resection: a multicenter analysis in Korea.
AB  - BACKGROUND: Solid pseudopapillary tumors (SPTs) of the pancreas are still
      considered a surgical enigma. Many clinical research trials have failed to
      identify prognostic factors that predict the malignant behavior of SPTs.
      MATERIALS AND METHODS: This work was a retrospective multicenter study that
      included a total of 17 medical institutions. Data from 351 patients who underwent
      surgical resection from January 1990 to December 2008 were retrospectively
      collected using standardized case report forms requesting clinicopathologic
      features. RESULTS: Thirty-four patients (9.7%) were male, and 317 (90.3%) were
      female, with a mean age of 36.8 +/- 12.4 years. Recently, minimally invasive (P <
      0.001) and parenchyma or function-preserving limited surgeries (P = 0.016) have
      been more frequently applied for the treatment of pancreatic SPTs. Ninety-eight
      patients (27.9%) had microscopic malignant features. Only 9 patients (2.6%)
      experienced tumor recurrence after the initial pancreatic SPT resection.
      Multivariate analysis showed that a tumor size larger than 8 cm [Exp (beta) =
      7.385, P = 0.018], microscopic malignant features [Exp (beta) = 10.009, P =
      0.011], and stage IV [Exp (beta) = 42.003, P = 0.002] were significant prognostic
      factors for tumor recurrence. When combined with stage IV, the microscopic
      malignant features and 2010 World Health Organization definition of solid
      pseudopapillary carcinoma more successfully differentiated future recurrence risk
      groups (P < 0.001). CONCLUSIONS: More specific pathologic descriptions need to be
      employed in pathologic report forms to provide proper information to predict SPT
      recurrence after resection. Future studies emphasizing the standardized
      pathologic evaluation of pancreatic SPTs may unveil the enigmatic nature of
      pancreatic SPTs.

PMID- 24743623
TI  - Methods of quality assurance in multicenter trials in laparoscopic colorectal
      surgery: a systematic review.
AB  - OBJECTIVES: To assess the risk of bias in multicenter randomized controlled
      trials (RCTs) investigating laparoscopic colorectal cancer surgery and review the
      use of quality assurance mechanisms to reduce performance bias. BACKGROUND: RCTs
      represent the criterion standard comparison for health care interventions. For
      trials investigating interventional techniques, performance bias can arise
      through variation in delivery of the intervention. METHODS: A comprehensive
      systematic review was undertaken using MEDLINE and EMBASE databases to identify
      all large RCTs investigating laparoscopic colorectal cancer surgery. Risk of
      performance bias was evaluated through assessment of publications and protocols
      to identify methods used for quality assurance of surgical technique. In
      addition, the Cochrane Collaboration's "risk of bias" tool was used to evaluate
      other potential sources of bias. RESULTS: The literature search identified 48
      publications, reporting upon 8 individual RCTs. All studies used mechanisms for
      quality assurance of laparoscopic colorectal surgery. Methods employed included
      credentialing of surgeons or units through assessment of experience and
      expertise, standardization of surgical technique, and monitoring. None report the
      use of structure objective assessment tools for accrediting expertise. All 8 were
      assessed as low risk of bias using the Cochrane tool. A framework is proposed for
      use as a model for quality assurance in future surgical trials. CONCLUSIONS:
      Consideration of risk of performance bias is important when appraising trials
      investigating an interventional technique. Laparoscopic colorectal surgery RCTs
      have all employed quality assurance mechanisms to reduce risk of performance
      bias. Further research is indicated to investigate adopting objective assessment
      tools for quality assurance within multicenter RCTs.

PMID- 24743624
TI  - Prehospital helicopter transport and survival of patients with traumatic brain
      injury.
AB  - OBJECTIVE: To investigate the association of helicopter transport with survival
      of patients with traumatic brain injury (TBI), in comparison with ground
      emergency medical services (EMS). BACKGROUND: Helicopter utilization and its
      effect on the outcomes of TBI remain controversial. METHODS: We performed a
      retrospective cohort study involving patients with TBI who were registered in the
      National Trauma Data Bank between 2009 and 2011. Regression techniques with
      propensity score matching were used to investigate the association of helicopter
      transport with survival of patients with TBI, in comparison with ground EMS.
      RESULTS: During the study period, there were 209,529 patients with TBI who were
      registered in the National Trauma Data Bank and met the inclusion criteria. Of
      these patients, 35,334 were transported via helicopters and 174,195 via ground
      EMS. For patients transported to level I trauma centers, 2797 deaths (12%) were
      recorded after helicopter transport and 8161 (7.8%) after ground EMS.
      Multivariable logistic regression analysis demonstrated an association of
      helicopter transport with increased survival [OR (odds ratio), 1.95; 95%
      confidence interval (CI), 1.81-2.10; absolute risk reduction (ARR), 6.37%]. This
      persisted after propensity score matching (OR, 1.88; 95% CI, 1.74-2.03; ARR,
      5.93%). For patients transported to level II trauma centers, 1282 deaths (10.6%)
      were recorded after helicopter transport and 5097 (7.3%) after ground EMS.
      Multivariable logistic regression analysis demonstrated an association of
      helicopter transport with increased survival (OR, 1.81; 95% CI, 1.64-2.00; ARR
      5.17%). This again persisted after propensity score matching (OR, 1.73; 95% CI,
      1.55-1.94; ARR, 4.69). CONCLUSIONS: Helicopter transport of patients with TBI to
      level I and II trauma centers was associated with improved survival, in
      comparison with ground EMS.

PMID- 24743625
TI  - Genetic variants of microRNA sequences and susceptibility to sepsis in patients
      with major blunt trauma.
AB  - OBJECTIVE: The objective of this study was to conduct a systematic survey of
      common precursor microRNA (pre-miRNA) single nucleotide polymorphisms (SNPs) and
      evaluate their clinical relevance in patients with major blunt trauma.
      BACKGROUND: Recent evidence indicates that small noncoding RNA molecules known as
      miRNAs can function as important negative gene regulators and are implicated in
      the pathogenesis of various diseases. METHODS: We conducted a 2-stage study to
      examine the impact of 9 selected SNPs with potential functional significance on
      the susceptibility to sepsis of 1268 trauma patients (1 screening cohort, n =
      666) and 2 independent validated cohorts (n = 286 and n = 316, respectively) in
      China. RESULTS: Among the 9 selected SNPs with potential functional significance,
      only 1 (miR-608 rs4919510) was found to be strongly associated with a higher risk
      of developing sepsis and multiple organ dysfunction in all 3 independent study
      cohorts. An even stronger association was observed for the rs4919510 polymorphism
      when combining these 3 study cohorts together. In addition, the rs4919510
      polymorphism showed a significant correlation with a higher production of
      proinflammatory cytokines and a lower production of anti-inflammatory cytokines.
      In vitro experiments further indicated that the G->C variant of this polymorphism
      could significantly increase the expression of mature miR-608. CONCLUSIONS: Our
      results indicate that the rs4919510G/C SNP in hsa-mir-608 may be a prognostic
      biomarker for sepsis in patients with major trauma. Further characterization of
      miRNA SNPs may open new avenues for studying sepsis and developing novel
      therapeutic approaches.

PMID- 24743626
TI  - Reply to Letter: "Does the Robot Provide an Advantage Over Laparoscopic Liver
      Resection?".

PMID- 24743627
TI  - Reply to the letter: "anatomic resection of hepatocellular carcinoma: a step
      forward for the precise resection of the tumor-bearing portal territory of the
      liver".

PMID- 24743628
TI  - Metabolic score: insights on the development and prediction of remission of
      metabolic syndrome after gastric bypass.
AB  - INTRODUCTION: Metabolic syndrome (MetS) clusters the most dangerous
      cardiovascular disease risk factors. Although insulin resistance and central
      obesity play an important role in the pathogenesis, the factors that determine
      its development and ultimate remission after Roux-en-Y gastric bypass (RYGB) are
      not fully understood. METHODS: We recruited a prospective cohort of 210
      consecutive patients after RYGB between January 2010 and December 2011. Patients
      were evaluated clinically and with a biochemical profile preoperatively and at 12
      months after surgery. Visceral adipose tissue and subcutaneous abdominal adipose
      tissue samples were collected at surgical intervention. We aimed to identify
      factors associated with MetS in morbidly obese patients and predictors of its
      remission 12 months after RYGB. RESULTS: Increasing age (>40 years), male sex,
      alanine aminotransferase levels and visceral adipose tissue/subcutaneous
      adipocyte size ratio were independently related to the expression of MetS at the
      moment of surgery.One year after RYGB, there was a significant decrease in the
      prevalence of MetS (63.3%-10%; P < 0.001) and in each of its components. A
      multivariable analysis for the remission of MetS identified that only fasting
      glucose levels (OR = 13.4; P = 0.01) and duration of obesity (OR = 1.08; P =
      0.04) were independently related to the persistence of MetS. A metabolic score
      (scale of 1-10), consisting of duration of obesity, fasting blood glucose levels,
      the presence of high blood pressure and low levels of high-density lipoprotein
      identified 4 different risk categories for the persistence of MetS (area under
      the curve = 0.848). CONCLUSIONS: The metabolic score can be used to predict the
      remission of MetS after RYGB with high accuracy. Patients in high-risk groups
      might be managed more aggressively and low-risk patients may have their
      medication discontinued earlier with extra safety.

PMID- 24743629
TI  - Are we paying our housestaff fairly?

PMID- 24743630
TI  - The Long-awaited Comparative Study on Thermal Ablation Technologies Is Finally
      Out!

PMID- 24743631
TI  - Surgical treatment of complex small bowel Crohn disease.
AB  - INTRODUCTION: The clinical presentations of Crohn disease of the small bowel vary
      from low to high complexity. Understanding the complexity of Crohn disease of the
      small bowel is important for the surgeon and the gastroenterologist caring for
      the patient and may be relevant for clinical research as a way to compare
      outcomes. Here, we present a categorization of complex small bowel Crohn disease
      and review its surgical treatment as a potential initial step toward the
      establishment of a definition of complex disease. RESULTS: The complexity of
      small bowel Crohn disease can be sorted into several categories: technical
      challenges, namely, fistulae, abscesses, bowel or ureteral obstruction,
      hemorrhage, cancer and thickened mesentery; extensive disease; the presence of
      short gut; a history of prolonged use of medications, particularly steroids,
      immunomodulators, and biological agents; and a high risk of recurrence.
      CONCLUSIONS: Although the principles of modern surgical treatment of Crohn
      disease have evolved to bowel conservation such as strictureplasty techniques and
      limited resection margins, such practices by themselves are often not sufficient
      for the management of complex small bowel Crohn disease. This manuscript reviews
      each category of complex small bowel Crohn disease, with special emphasis on
      appropriate surgical strategy.

PMID- 24743632
TI  - Signs of cardiac autonomic imbalance and proarrhythmic remodeling in FTO
      deficient mice.
AB  - In humans, variants of the fat mass and obesity associated (FTO) gene have
      recently been associated with obesity. However, the physiological function of FTO
      is not well defined. Previous investigations in mice have linked FTO deficiency
      to growth retardation, loss of white adipose tissue, increased energy metabolism
      and enhanced systemic sympathetic activation. In this study we investigated for
      the first time the effects of global knockout of the mouse FTO gene on cardiac
      function and its autonomic neural regulation. ECG recordings were acquired via
      radiotelemetry in homozygous knockout (n = 12) and wild-type (n = 8) mice during
      resting and stress conditions, and analyzed by means of time- and frequency
      domain indexes of heart rate variability. In the same animals, cardiac
      electrophysiological properties (assessed by epicardial mapping) and structural
      characteristics were investigated. Our data indicate that FTO knockout mice were
      characterized by (i) higher heart rate values during resting and stress
      conditions, (ii) heart rate variability changes (increased LF to HF ratio), (iii)
      larger vulnerability to stress-induced tachyarrhythmias, (iv) altered ventricular
      repolarization, and (v) cardiac hypertrophy compared to wild-type counterparts.
      We conclude that FTO deficiency in mice leads to an imbalance of the autonomic
      neural modulation of cardiac function in the sympathetic direction and to a
      potentially proarrhythmic remodeling of electrical and structural properties of
      the heart.

PMID- 24743633
TI  - Small modifications to network topology can induce stochastic bistable spiking
      dynamics in a balanced cortical model.
AB  - Directed random graph models frequently are used successfully in modeling the
      population dynamics of networks of cortical neurons connected by chemical
      synapses. Experimental results consistently reveal that neuronal network topology
      is complex, however, in the sense that it differs statistically from a random
      network, and differs for classes of neurons that are physiologically different.
      This suggests that complex network models whose subnetworks have distinct
      topological structure may be a useful, and more biologically realistic,
      alternative to random networks. Here we demonstrate that the balanced excitation
      and inhibition frequently observed in small cortical regions can transiently
      disappear in otherwise standard neuronal-scale models of fluctuation-driven
      dynamics, solely because the random network topology was replaced by a complex
      clustered one, whilst not changing the in-degree of any neurons. In this network,
      a small subset of cells whose inhibition comes only from outside their local
      cluster are the cause of bistable population dynamics, where different clusters
      of these cells irregularly switch back and forth from a sparsely firing state to
      a highly active state. Transitions to the highly active state occur when a
      cluster of these cells spikes sufficiently often to cause strong unbalanced
      positive feedback to each other. Transitions back to the sparsely firing state
      rely on occasional large fluctuations in the amount of non-local inhibition
      received. Neurons in the model are homogeneous in their intrinsic dynamics and in
      degrees, but differ in the abundance of various directed feedback motifs in which
      they participate. Our findings suggest that (i) models and simulations should
      take into account complex structure that varies for neuron and synapse classes;
      (ii) differences in the dynamics of neurons with similar intrinsic properties may
      be caused by their membership in distinctive local networks; (iii) it is
      important to identify neurons that share physiological properties and location,
      but differ in their connectivity. 

PMID- 24743634
TI  - An integrated approach combining chemical analysis and an in vivo bioassay to
      assess the estrogenic potency of a municipal solid waste landfill leachate in
      Qingdao.
AB  - Various adverse effects related to landfill leachate have made leachates an
      important issue in past decades, and it has been demonstrated that landfill
      leachate is an important source of environmental estrogens. In this study, we
      employed chemical analysis of some already evaluated estrogenic substances, in
      combination with a bioassay using several specific biomarkers (e.g., plasma
      vitellogenin and sex steroids, enzyme activity of gonad gamma-glutamyl
      transpeptidase, and gonadosomatic index) to evaluate the estrogenic activities in
      outlets from different stages of the leachate treatment process. The results
      indicated that 5 environmental estrogens (4-t-octylphenol, bisphenol A, di-ethyl
      phthalate, di-n-butyl phthalate, and diethylhexyl phthalate) were detected by a
      gas chromatography-mass spectrometry, and the concentrations in leachate samples
      were 6153 ng/L, 3642 ng/L, 2139 ng/L, 5900 ng/L, and 9422 ng/L, respectively.
      Leachate (1?200 diluted) induced the synthesis of plasma vitellogenin and led to
      decreased enzyme activity of gonad gamma-glutamyl transpeptidase and
      gonadosomatic index in male goldfish (Carassius auratus) after a 28-day exposure,
      while increased circulating 17beta-estradiol level was also observed in males
      exposed to treated effluent. Although the target EEs were partially removed with
      removal rates varying from 87.2% to 99.77% by the "membrane bioreactor+reverse
      osmosis+aeration zeolite biofilter" treatment process, the treated effluent is
      still estrogenic to fish. The method combined chemical techniques with the
      responses of test organisms allowing us to identify the group of estrogen-like
      chemicals so that we were able to evaluate the overall estrogenic effects of a
      complex mixture, avoiding false negative assessments.

PMID- 24743635
TI  - Associations between autofluorescence abnormalities and visual acuity in
      idiopathic macular telangiectasia type 2: MacTel project report number 5.
AB  - PURPOSE: The aim of this study was to determine whether typical abnormalities
      seen on autofluorescence (AF) imaging in patients with macular telangiectasia
      (MacTel) type 2 are correlated with visual acuity at presentation and with
      progression of visual loss over a 2-year follow-up period. METHODS: A subgroup of
      218 patients (413 eyes) enrolled in the MacTel study that underwent AF imaging
      was included in the present study. Images were graded at the Moorfields Eye
      Hospital Reading Center. Recorded AF abnormalities at baseline and at 2 years
      included the presence of increased AF because of loss of masking at the central
      macula, localized decreased AF at the end of a retinal vessel, and large area of
      decreased AF. Best-corrected visual acuity was measured using the Early Treatment
      for Diabetic Retinopathy chart at baseline and after 2 years. Statistical
      associations were sought by means of a generalized linear model. RESULTS:
      Presence of increased macular AF (P = 0.004), a large area of decreased AF (P <
      0.001), or decreased AF at the end of a retinal vessel (P < 0.001) at baseline
      were significantly associated with worse best-corrected visual acuity. Presence
      of increased macular AF (P < 0.001) or of localized decreased AF at the end of a
      retinal vessel (P < 0.001) and the absence of a large area of decreased AF (P <
      0.001) were predictive of a subtle but significant drop in best-corrected visual
      acuity at 2 years. CONCLUSIONS: Increased central AF at baseline heralds worse
      best-corrected visual acuity and predicts further subtle visual loss in a period
      of 2 years, which, however, does not stand out from the overall slowly
      progressive natural history of the disease.

PMID- 24743636
TI  - Multimodal imaging and multifocal electroretinography demonstrate autosomal
      recessive Stargardt disease may present like occult macular dystrophy.
AB  - PURPOSE: To describe multimodal imaging and electrophysiologic characteristics of
      an unusual subset of patients with genetically confirmed autosomal recessive
      Stargardt disease (STGD1) who exhibited a central form of cone dysfunction
      resembling occult macular dystrophy that preceded the development of lipofuscin
      flecks, atrophy of retinal pigment epithelium (RPE), or full-field
      electroretinography abnormalities. METHODS: Retrospective, observational
      descriptive case series. RESULTS: Five patients with compound heterozygous ABCA4
      mutations presented with bilateral visual acuity reduction, normal-appearing
      fundi, and blocked choroidal fluorescence on fluorescein angiography. One sibling
      each of two probands with identical genotypes was also included for analysis.
      Full-field electroretinography testing was normal in all patients, but multifocal
      electroretinography demonstrated centripetally depressed amplitudes exceeding
      areas of fundus autofluorescence, infrared imaging, and spectral domain optical
      coherence tomography abnormalities. Spectral domain optical coherence tomography
      initially revealed disruption of the inner segment ellipsoid band accompanying an
      ovoid hypofluorescent foveolar lesion. Progression to later stages was
      accompanied by the loss of the foveal photoreceptor outer segments, creating
      foveal cavitation with preservation of the RPE. Fundus autofluorescence and
      infrared imaging demonstrated corresponding bull's eye lesions. Over time, the
      foveal potential space on spectral domain optical coherence tomography collapsed,
      and three patients developed RPE atrophy and visible lipofuscin flecks. The
      flecks were detectable by fundus autofluorescence and infrared imaging earlier
      than by biomicroscopy. From these findings, a staging system for this subset of
      Stargardt disease presenting with central cone dysfunction was developed and
      presented herein. CONCLUSION: Autosomal recessive Stargardt disease may present
      as a central cone dysfunction syndrome before the development of lipofuscin
      flecks, atrophy of RPE, or full-field electroretinography abnormalities. If
      emerging therapies for Stargardt disease succeed, early recognition and treatment
      of patients with preserved foveal photoreceptor and RPE cell bodies may yield a
      more favorable visual prognosis.

PMID- 24743637
TI  - Clinical manifestations of central retinal artery occlusion in eyes of
      proliferative diabetic retinopathy with previous vitrectomy and panretinal
      photocoagulation.
AB  - PURPOSE: To report the clinical characteristics of central retinal artery
      occlusion in eyes of proliferative diabetic retinopathy with previous vitrectomy
      and panretinal photocoagulation. METHODS: Retrospective case series. RESULTS:
      Twelve eyes in 12 patients (4 women and 8 men) with a mean age of 55.3 +/- 6.2
      years of age were included in this study. All patients had successful previous
      surgery for complications of proliferative diabetic retinopathy and complete
      panretinal photocoagulation performed. All patients had sudden visual
      deterioration and fluorescein angiography confirmed central retinal artery
      occlusion. Prominent cherry-red spot was noted in only two eyes. The other eyes
      either had less prominent or incomplete, or invisible cherry-red spots.
      Sequential optical coherence tomography in 7 of the 12 eyes showed increased
      optical reflectivity at inner retinal layer in 6 of the 7 eyes. Rubeosis iridis
      developed later in six eyes and neovascular glaucoma in four eyes. Vision
      worsening was noted in five eyes, improved in three eyes, and stable in four eyes
      after an averaged follow-up of 4 months. CONCLUSION: Less typical cherry-red
      spots, higher possibility of rubeosis despite previous complete panretinal
      photocoagulation, are the characteristic features of central retinal artery
      occlusion in patients with proliferative diabetic retinopathy with previous
      vitrectomy.

PMID- 24743638
TI  - Risk of central serous chorioretinopathy in adults prescribed oral
      corticosteroids: a population-based study in Taiwan.
AB  - PURPOSE: To investigate the incidence and risk factors for central serous
      chorioretinopathy (CSCR) in adults who use oral corticosteroids in Taiwan.
      METHODS: This is a population-based nested case-control study between 2000 and
      2008. From the Taiwan National Health Insurance Research Database, adults who
      were repetitively prescribed oral corticosteroids were included as the study
      cohort. Of those, newly diagnosed CSCR cases were identified and the CSCR
      incidence was calculated. Subjects matched for age, gender, and the enrollment
      time were randomly selected as the controls. Corticosteroids use was compared
      between the cases and controls. Poisson and conditional logistic regressions were
      used to analyze the potential risk factors for CSCR. RESULTS: Among 142,035 oral
      corticosteroids users, 320 cases of CSCR were identified, and 1,554 matched
      controls were randomly selected. The incidence rate of CSCR was 44.4 (95%
      confidence interval, 39.5-49.3) cases per 100,000 person-years. Multivariate
      Poisson regression showed that male patients and those aged 35 years to 44 years
      had significantly higher incidence rates of CSCR. There were no differences in
      either median dosage or mean duration of systemic corticosteroid treatment
      between the cases and controls. After adjusting for other confounders, current
      use of oral corticosteroids was found to be significantly associated with the
      risk of CSCR (odds ratio, 2.40; 95% confidence interval, 1.49-3.89). CONCLUSION:
      Male gender, middle age, and current use of oral corticosteroids were found to be
      the risk factors for CSCR. However, oral corticosteroids dosage and treatment
      duration were not associated with the CSCR risk.

PMID- 24743639
TI  - Relationship between presence of foveal bulge in optical coherence tomographic
      images and visual acuity after rhegmatogenous retinal detachment repair.
AB  - PURPOSE: To determine whether a significant correlation exists between the
      presence of a bulge in the photoreceptor inner segment/outer segment line and the
      best-corrected visual acuity in eyes after successful rhegmatogenous retinal
      detachment (RRD) repair. METHODS: Patients who had undergone successful RRD
      repair and had an intact inner segment/outer segment line at the central fovea in
      the spectral-domain optical coherence tomographic images were retrospectively
      studied. Thirty-five eyes of 35 patients were evaluated, and the eyes were
      classified preoperatively into those with macula-on RRD (n = 14) and those with
      macula-off RRD (n = 21). Examination of the spectral-domain optical coherence
      tomographic images of normal eyes showed that the inner segment/outer segment
      line has a bulge at the central fovea. The 35 eyes with successful retinal
      reattachment were classified by the presence or absence of foveal bulge. RESULTS:
      The presence of foveal bulge differed significantly between macula-on RRD (100%)
      and macula-off RRD group (28.6%; P < 0.0001). In the macula-off RRD group, the
      best-corrected visual acuity was significantly better in eyes with a foveal bulge
      than in eyes without a foveal bulge (P = 0.0028). CONCLUSION: The foveal bulge is
      a good marker to determine the functional properties of the fovea in eyes with
      successful RRD repair.

PMID- 24743640
TI  - Enhanced depth imaging optical coherence tomography of choroidal metastasis in 14
      eyes.
AB  - PURPOSE: To describe the imaging features of choroidal metastasis using enhanced
      depth imaging optical coherence tomography (EDI-OCT). METHODS: This retrospective
      observational case series included 31 eyes with choroidal metastasis. Spectral
      domain EDI-OCT was performed using Heidelberg Spectralis HRA + OCT. The main
      outcome measures were imaging features by EDI-OCT. RESULTS: Of 31 eyes with
      choroidal metastasis imaged with EDI-OCT, 14 (45%) eyes displayed image detail
      suitable for study. The metastasis originated from carcinoma of the breast (n =
      7, 50%), lung (n = 5, 36%), pancreas (n = 1, 7%), and thyroid gland (n = 1, 7%).
      The mean tumor basal diameter was 6.4 mm, and mean thickness was 2.3 mm by B-scan
      ultrasonography. The tumor location was submacular in 6 (43%) eyes and
      extramacular in 8 (57%) eyes. By EDI-OCT, the mean tumor thickness was 987 MUm.
      The most salient EDI-OCT features of the metastasis included anterior
      compression/obliteration of the overlying choriocapillaris (n = 13, 93%), an
      irregular (lumpy bumpy) anterior contour (n = 9, 64%), and posterior shadowing (n
      = 12, 86%). Overlying retinal pigment epithelial abnormalities were noted (n =
      11, 78%). Outer retinal features included structural loss of the interdigitation
      of the cone outer segment tips (n = 9, 64%), the ellipsoid portion of
      photoreceptors (n = 8, 57%), external limiting membrane (n = 4, 29%), outer
      nuclear layer (n = 1, 7%), and outer plexiform layer (n = 1, 7%). The inner
      retinal layers (inner nuclear layer to nerve fiber layer) were normal. Subretinal
      fluid (n = 11, 79%), subretinal lipofuscin pigment (n = 1, 7%), and intraretinal
      edema (n = 2, 14%) were identified. CONCLUSION: The EDI-OCT of choroidal
      metastasis shows a characteristic lumpy bumpy anterior tumor surface and outer
      retinal layer disruption with preservation of inner retinal layers.

PMID- 24743641
TI  - Elevated hydrogen sulfide levels in vitreous body and plasma in patients with
      proliferative diabetic retinopathy.
AB  - PURPOSE: Hydrogen sulfide (H2S), a colorless gas, has been confirmed to be a
      gaseous messenger molecule and an endogenous stimulus for angiogenesis recently.
      This study was performed to investigate the role of H2S in diabetic retinopathy.
      METHODS: Blood samples were collected from normal controls and patients with
      diabetes. Vitreous samples were collected from patients with proliferative
      diabetic retinopathy (PDR) and patients with rhegmatogenous retinal detachment.
      Patients were grouped into diabetic patients without diabetic retinopathy (non
      DR), with nonproliferative DR, and with PDR. Concentrations of H2S and vascular
      endothelial growth factor in the plasma and vitreous body were detected using a
      spectrophotometer. RESULTS: A decreased H2S level in the plasma was observed in
      non-DR group (41.89 +/- 8.52 MUM, P < 0.05), and an increased H2S level in the
      plasma was observed in PDR group (60.49 +/- 11.14 MUM, P < 0.001), when compared
      with that in normal controls (49.67 +/- 9.72 MUM). There was no difference in
      plasma H2S level between patients with nonproliferative DR (54.13 +/- 8.61 MUM)
      and normal controls. In the vitreous body, H2S levels in PDR group were
      significantly higher (76.80 +/- 24.08 MUM, P < 0.001) than that in rhegmatogenous
      retinal detachment group (24.37 +/- 11.25 MUM). Levels of vascular endothelial
      growth factor in plasma from patients with diabetes were significantly lower (P <
      0.001) than that in normal controls. Vascular endothelial growth factor levels in
      the vitreous body from diabetic patients with PDR were significantly higher
      (885.61 +/- 190.41 pg/mL, P < 0.001) than that from patients with rhegmatogenous
      retinal detachment (89.98 +/- 19.56 pg/mL). Seven days after an intravitreal
      injection of ranibizumab, a significantly decreased H2S level (55.58 +/- 7.20
      MUM, P < 0.05) was observed in the vitreous body in patients with PDR when
      compared with that (75.07 +/- 12.95 MUM) in the vitreous body collected just
      before intravitreal injection. CONCLUSION: These results indicated that anti
      vascular endothelial growth factor may downregulate the H2S level in the vitreous
      body, and H2S may play a role in the development of DR. Hydrogen sulfide may be a
      novel target for the therapy of DR.

PMID- 24743642
TI  - Clinical features and incidence rate of ocular complications in punctate inner
      choroidopathy.
AB  - PURPOSE: To study the clinical features and incidence rate of ocular
      complications in patients with punctate inner choroidopathy. METHODS: This is a
      retrospective cohort study conducted in a single-center academic practice
      setting. Patients diagnosed with punctate inner choroidopathy at the Wilmer Eye
      Institute, Johns Hopkins University from 1984 to 2012 were identified.
      Demographics and clinical features including the presence of choroidal
      neovascularization (CNV) and structural complications were collected. Main
      outcome measures, including visual impairment and incidence rate of ocular
      complications, were analyzed. RESULTS: Thirty-one patients (59 eyes) were
      included in the study. Follow-up data were available for 24 patients (47 eyes)
      with a mean follow-up time of 3.4 years (range, 2 months to 8.7 years). In the
      affected eyes with follow-up, the incidence rate of visual impairment to 20/50 or
      worse was 0.06 per eye-year (EY) (95% confidence interval, 0.022/EY-0.114/EY).
      The incidence rate of visual loss to 20/200 or worse was 0.006/EY (95% confidence
      interval, 0.0001/EY-0.034/EY). Thirty-six eyes (77%) had an ultimate visual
      acuity of 20/40 or better. All of the 13 patients with more than >= 3 years of
      follow-up had a visual acuity of >= 20/40 in at least 1 eye at 3 years after
      presentation. Two thirds of the follow-up patients (67%) on immunomodulatory drug
      therapy did not have new or recurrent CNV. However, this was not a statistically
      significant difference. Three eyes with follow-up had recurrence of CNV for an
      incidence rate of 0.04/EY (95% confidence interval, 0.008/EY-0.12/EY). Two eyes
      developed new CNV during follow-up for an incidence rate of 0.02/EY (95%
      confidence interval, 0.002/EY-0.066/EY). CONCLUSION: The visual prognosis in most
      cases of punctate inner choroidopathy is very good. The incidence rate of new CNV
      and recurrent CNV was 0.02/EY and 0.04/EY, respectively.

PMID- 24743644
TI  - In pursuit of the gene: an interview with James Schwartz.

PMID- 24743643
TI  - Late recurrence of myopic foveoschisis after successful repair with primary
      vitrectomy and incomplete membrane peeling.
AB  - PURPOSE: To report three cases of late recurrence of myopic foveoschisis (MF)
      after initial successful repair with pars plana vitrectomy and membrane peeling
      to assess the importance of internal limiting membrane peeling. METHODS: A
      retrospective noncomparative case series was performed of patients who underwent
      a primary pars plana vitrectomy by a single surgeon with successful resolution of
      MF, but eventually underwent repeat pars plana vitrectomy for recurrent MF. Best
      corrected visual acuity, fundus photography, and optical coherence tomography
      were obtained at each examination. RESULTS: Three eyes of three patients
      underwent pars plana vitrectomy for recurrent MF. Myopic foveoschisis recurrence
      occurred 6, 3.5, and 12 years after the primary vitrectomy, respectively. Repeat
      vitrectomy with staining and additional peeling of the internal limiting membrane
      resulted in good anatomical outcome and stabilization of visual acuity in all
      cases. CONCLUSION: Late recurrence of MF after successful primary vitrectomy is
      described. Fibrocellular proliferation on residual cortical vitreous or
      incomplete internal limiting membrane peeling during the initial vitrectomy may
      underlie recurrence.

PMID- 24743645
TI  - Development of a Set of Indicators to Evaluate Injury Control Research Centers.
AB  - BACKGROUND: Few methods have been defined for evaluating the individual and
      collective impacts of academic research centers. In this project, with input from
      injury center directors, we systematically defined indicators to assess the
      progress and contributions of individual Injury Control Research Centers (ICRCs)
      and, ultimately, to monitor progress of the overall injury center program.
      METHOD: We used several methods of deriving a list of recommended priority and
      supplemental indicators. This included published literature review, telephone
      interviews with selected federal agency staff, an e-mail survey of injury center
      directors, an e-mail survey of staff at the Centers for Disease Control and
      Prevention, a two-stage Delphi process (e-mailed), and an in-person focus group
      with injury center directors. We derived the final indicators from an analysis of
      ratings of potential indicators by center directors and CDC staff. We also
      examined qualitative responses to open-ended items that address conceptual and
      implementation issues. RESULTS: All currently funded ICRCs participated in at
      least one part of the process, resulting in a list of 27 primary indicators (some
      with subcomponents), 31 supplemental indicators, and multiple suggestions for
      using the indicators. CONCLUSION: Our results support an approach that combines
      standardized definitions and quantifiable indicators with qualitative reporting,
      which allows consideration of center distinctions and priorities. The center
      directors urged caution in using the indicators, given funding constraints and
      recognition of unique institutional environments. While focused on injury
      research centers, we suggest these indicators also may be useful to academic
      research centers of other types.

PMID- 24743646
TI  - Grief, Anger, and Relationality: The Impact of a Research-Based Theater
      Intervention on Emotion Work Practices in Brain Injury Rehabilitation.
AB  - BACKGROUND: Therapeutic emotion work is performed by health care providers as
      they manage their own feelings as well as those of colleagues and patients as
      part of efforts to improve the physical and psychosocial health outcomes of
      patients. It has yet to be examined within the context of traumatic brain injury
      rehabilitation. OBJECTIVE: To evaluate the impact of a research-based theater
      intervention on emotion work practices of neurorehabilitation staff. RESEARCH
      DESIGN: Data were collected at baseline and at 3 and 12 months postintervention
      in the inpatient neurorehabilitation units of two rehabilitation hospitals in
      central urban Canada. SUBJECTS: Participants (N = 33) were recruited from
      nursing, psychology, allied health, recreational therapy, and chaplaincy.
      MEASURES: Naturalistic observations (N = 204.5 hr) of a range of structured and
      unstructured activities in public and private areas, and semistructured
      interviews (N = 87) were conducted. RESULTS: Preintervention analysis indicated
      emotion work practices were characterized by stringent self-management of
      empathy, suppression of client grief, adeptness with client anger, and discomfort
      with reactions of family and spouses. Postintervention analysis indicated
      significant staff changes in a relationality orientation, specifically
      improvements in outreach to homosexual and heterosexual family care partners, and
      support for sexual orientation and intimacy expression. No improvements were
      demonstrated in grief support. CONCLUSION: Emotion work has yet to be the focus
      of initiatives to improve neurorehabilitative care. Our findings suggest the
      dramatic arts are well positioned to improve therapeutic emotion work and effect
      cultures of best practice. Recommendations are made for interprofessional
      educational initiatives to improve responses to client grief and potential
      intimate partner violence.

PMID- 24743647
TI  - Caenorhabditis elegans neuromuscular junction: GABA receptors and ivermectin
      action.
AB  - The prevalence of human and animal helminth infections remains staggeringly high,
      thus urging the need for concerted efforts towards this area of research. GABA
      receptors, encoded by the unc-49 gene, mediate body muscle inhibition in
      Caenorhabditis elegans and parasitic nematodes and are targets of anthelmintic
      drugs. Thus, the characterization of nematode GABA receptors provides a
      foundation for rational anti-parasitic drug design. We therefore explored UNC-49
      channels from C. elegans muscle cultured cells of the first larval stage at the
      electrophysiological and behavioral levels. Whole-cell recordings reveal that
      GABA, muscimol and the anthelmintic piperazine elicit macroscopic currents from
      UNC-49 receptors that decay in their sustained presence, indicating full
      desensitization. Single-channel recordings show that all drugs elicit openings of
      ~2.5 pA (+100 mV), which appear either as brief isolated events or in short
      bursts. The comparison of the lowest concentration required for detectable
      channel opening, the frequency of openings and the amplitude of macroscopic
      currents suggest that piperazine is the least efficacious of the three drugs.
      Macroscopic and single-channel GABA-activated currents are profoundly and
      apparently irreversibly inhibited by ivermectin. To gain further insight into
      ivermectin action at C. elegans muscle, we analyzed its effect on single-channel
      activity of the levamisol-sensitive nicotinic receptor (L-AChR), the excitatory
      receptor involved in neuromuscular transmission. Ivermectin produces a profound
      inhibition of the frequency of channel opening without significant changes in
      channel properties. By revealing that ivermectin inhibits C. elegans muscle GABA
      and L-AChR receptors, our study adds two receptors to the already known
      ivermectin targets, thus contributing to the elucidation of its pleiotropic
      effects. Behavioral assays in worms show that ivermectin potentiates piperazine
      induced paralysis, thus suggesting that their combination is a good strategy to
      overcome the increasing resistance of parasites, an issue of global concern for
      human and animal health. 

PMID- 24743648
TI  - TCR affinity associated with functional differences between dominant and
      subdominant SIV epitope-specific CD8+ T cells in Mamu-A*01+ rhesus monkeys.
AB  - Many of the factors that contribute to CD8+ T cell immunodominance hierarchies
      during viral infection are known. However, the functional differences that exist
      between dominant and subdominant epitope-specific CD8+ T cells remain poorly
      understood. In this study, we characterized the phenotypic and functional
      differences between dominant and subdominant simian immunodeficiency virus (SIV)
      epitope-specific CD8+ T cells restricted by the major histocompatibility complex
      (MHC) class I allele Mamu-A*01 during acute and chronic SIV infection. Whole
      genome expression analyses during acute infection revealed that dominant SIV
      epitope-specific CD8+ T cells had a gene expression profile consistent with
      greater maturity and higher cytotoxic potential than subdominant epitope-specific
      CD8+ T cells. Flow-cytometric measurements of protein expression and anti-viral
      functionality during chronic infection confirmed these phenotypic and functional
      differences. Expression analyses of exhaustion-associated genes indicated that
      LAG-3 and CTLA-4 were more highly expressed in the dominant epitope-specific
      cells during acute SIV infection. Interestingly, only LAG-3 expression remained
      high during chronic infection in dominant epitope-specific cells. We also
      explored the binding interaction between peptide:MHC (pMHC) complexes and their
      cognate TCRs to determine their role in the establishment of immunodominance
      hierarchies. We found that epitope dominance was associated with higher TCR:pMHC
      affinity. These studies demonstrate that significant functional differences exist
      between dominant and subdominant epitope-specific CD8+ T cells within MHC
      restricted immunodominance hierarchies and suggest that TCR:pMHC affinity may
      play an important role in determining the frequency and functionality of these
      cell populations. These findings advance our understanding of the regulation of T
      cell immunodominance and will aid HIV vaccine design. 

PMID- 24743649
TI  - Case fatality rate and length of hospital stay among patients with typhoid
      intestinal perforation in developing countries: a systematic literature review.
AB  - BACKGROUND: Typhoid fever remains a major health problem in the developing world.
      Intestinal perforation is a lethal complication and continues to occur in
      impoverished areas despite advances in preventive and therapeutic strategies.
      OBJECTIVES: To estimate the case fatality rate (CFR) and length of hospital stay
      among patients with typhoid intestinal perforation in developing countries. DATA
      SOURCES: Peer-reviewed publications listed in PubMed and Google Scholar. STUDY
      ELIGIBILITY: The publications containing data on CFR or length of hospitalization
      for typhoid fever from low, lower middle and upper middle income countries based
      on World Bank classification. Limits are English language, human research and
      publication date from 1st January 1991 to 31st December 2011. PARTICIPANTS:
      Subjects with reported typhoid intestinal perforation. INTERVENTIONS: None,
      standard practice as reported in the publication. STUDY APPRAISAL AND SYNTHESIS
      METHODS: Systematic literature review followed by meta-analysis after regional
      classification on primary data. Descriptive methods were applied on secondary
      data. RESULTS: From 42 published reports, a total of 4,626 hospitalized typhoid
      intestinal perforation cases and 706 deaths were recorded (CFR = 15.4%; 95% CI;
      13.0%-17.8%) with a significant regional differences. The overall mean length of
      hospitalization for intestinal perforation from 23 studies was 18.4 days (N =
      2,542; 95% CI; 15.6-21.1). LIMITATIONS: Most typhoid intestinal perforation
      studies featured in this review were from a limited number of countries.
      CONCLUSIONS: The CFR estimated in this review is a substantial reduction from the
      39.6% reported from a literature review for years 1960 to 1990. Aggressive
      resuscitation, appropriate antimicrobial coverage, and prompt surgical
      intervention may have contributed to decrease mortality. IMPLICATIONS: The
      quantification of intestinal perforation outcomes and its regional disparities as
      presented here is valuable in prioritizing and targeting typhoid-preventive
      interventions to the most affected areas.

PMID- 24743650
TI  - Identification and characterization of ABA receptors in Oryza sativa.
AB  - Abscisic acid (ABA) is an essential phytohormone that regulates plant stress
      responses. ABA receptors in Arabidopsis thaliana (AtPYLs) have been extensively
      investigated by structural, biochemical, and in vivo studies. In contrast,
      relatively little is known about the ABA signal transduction cascade in rice.
      Besides, the diversities of AtPYLs manifest that the information accumulated in
      Arabidopsis cannot be simply adapted to rice. Thus, studies on rice ABA receptors
      are compulsory. By taking a bioinformatic approach, we identified twelve ABA
      receptor orthologs in Oryza sativa (japonica cultivar-group) (OsPYLs), named
      OsPYL1-12. We have successfully expressed and purified OsPYL1-3, 6 and 10-12 to
      homogeneity, tested the inhibitory effects on PP2C in Oryza sativa (OsPP2C), and
      measured their oligomerization states. OsPYL1-3 mainly exhibit as dimers and
      require ABA to inhibit PP2C's activity. On the contrary, OsPYL6 retains in the
      monomer-dimer equilibrium state and OsPYL10-11 largely exist as monomers, and
      they all display an ABA-independent phosphatase inhibition manner. Interestingly,
      although OsPYL12 seems to be a dimer, it abrogates the phosphatase activity of
      PP2Cs in the absence of ABA. Toward a further understanding of OsPYLs on the ABA
      binding and PP2C inhibition, we determined the crystal structure of ABA-OsPYL2
      OsPP2C06 complex. The bioinformatic, biochemical and structural analysis of ABA
      receptors in rice provide important foundations for designing rational ABA
      analogues and breeding the stress-resistant rice for commercial agriculture. 

PMID- 24743651
TI  - 10-year risk for cardiovascular disease among male workers in small-sized
      industries.
AB  - BACKGROUND: Health management or health promotion programs are limited,
      particularly for workers in small-sized industries. OBJECTIVES: This study aimed
      to identify the 10-year cardiovascular disease (CVD) risk using the general
      Framingham Risk Score and examine predictors of CVD risk adjusted for age among
      male workers. METHODS: Routine health screening data and self-reported
      questionnaires were collected from 12 933 male workers in 1041 industries from
      2009 to 2011 in South Korea. RESULTS: The proportion of high CVD risk (Framingham
      Risk Score >20%) was 7.1% (n = 919). Most (83.5%) subjects were manufacturing
      workers, engaged in manual labor, with a mean (SD) age of 42.1 (9.2) years
      (range, 30-70 years). Younger workers were more likely to smoke cigarettes, drink
      alcohol heavily, and be physically inactive. A logistic regression analysis
      showed that after adjusting for age, occupation type, body mass index, physical
      activity, and alcohol consumption were significant predictors of 10-year CVD
      risk. CONCLUSION: To reduce CVD risk, education regarding lifestyle modification
      should be emphasized for small-sized industrial workers who are overweight,
      physically inactive, and heavy alcohol drinkers and who work as bus or taxi
      drivers. Careful attention is also needed for younger workers who are a latent
      risk group for the development of CVD.

PMID- 24743652
TI  - Cardiovascular risk factors in young adults: a literature review.
AB  - This extensive literature review focuses on cardiovascular risk factors in young
      adults, with an emphasis on hyperlipidemia and hypertension. Multiple studies
      have confirmed that hyperlipidemia and hypertension during young adulthood are
      associated with coronary heart disease (CHD) in later decades, and CHD is one
      type of cardiovascular disease. The primary risk factors identified in the
      literature that are predictive of CHD are age; gender; race/ethnicity; smoking
      status; high blood pressure; and elevated lipid levels, especially low-density
      lipoprotein cholesterol. The current guidelines are insufficient to address
      screening and treatment in young adults with cardiovascular risk factors. Future
      studies are warranted to confirm the extent of cardiovascular risks in young
      adults, which can then be targeted to this population for prevention and
      intervention strategies. 

PMID- 24743653
TI  - Low-dose levodopa protects nerve cells from oxidative stress and up-regulates
      expression of pCREB and CD39.
AB  - OBJECTIVE: This study aimed to investigate the influence of low-dose levodopa (L
      DOPA) on neuronal cell death under oxidative stress. METHODS: PC12 cells were
      treated with L-DOPA at different concentrations. We detected the L-DOPA induced
      reactive oxygen species (ROS). Meanwhile, MTT and LDH assay were performed to
      determine the proliferation and growth of PC12 cells with or without ROS
      scavenger. In addition, after pretreatment with L-DOPA at different
      concentrations alone or in combination with CD39 inhibitor, PC12 cells were
      incubated with hydrogen peroxide (H2O2) and the cell viability was evaluated by
      MTT and LDH assay. In addition, the expression of pCREB and CD39 was detected by
      immunofluorescence staining and Western blot assay in both cells and rat's brain
      after L-DOPA treatment. RESULTS: After treatment with L-DOPA for 3 days, the cell
      proliferation and growth were promoted when the L-DOPA concentration was <30 uM,
      while cell proliferation was comparable to that in control group when the L-DOPA
      concentration was >30 uM. Low dose L-DOPA could protect the PC12 cells from H2O2
      induced oxidative stress, which was compromised by CD39 inhibitor. In addition,
      the expression of CD39 and pCREB increased in both PC12 cells and rats' brain
      after L-DOPA treatment. CONCLUSIONS: L-DOPA at different concentrations has
      distinct influence on proliferation and growth of PC12 cells, and low dose (<30
      uM) L-DOPA protects PC12 cells against oxidative stress which might be related to
      the up-regulation of CD39 and pCREB expression.

PMID- 24743655
TI  - Transcriptomes and shRNA suppressors in a TP53 allele-specific model of early
      onset colon cancer in African Americans.
AB  - African Americans are disproportionately affected by early-onset, high-grade
      malignancies. A fraction of this cancer health disparity can be explained by
      genetic differences between individuals of African or European descent. Here the
      wild-type Pro/Pro genotype at the TP53Pro72Arg (P72R) polymorphism (SNP:
      rs1042522) is more frequent in African Americans with cancer than in African
      Americans without cancer (51% vs. 37%), and is associated with a significant
      increase in the rates of cancer diagnosis in African Americans. To test the
      hypothesis that Tp53 allele-specific gene expression may contribute to African
      American cancer disparities, TP53 hemizygous knockout variants were generated and
      characterized in the RKO colon carcinoma cell line, which is wild type for TP53
      and heterozygous at the TP53Pro72Arg locus. Transcriptome profiling, using
      RNAseq, in response to the DNA-damaging agent etoposide revealed a large number
      of Tp53-regulated transcripts, but also a subset of transcripts that were
      TP53Pro72Arg allele specific. In addition, a shRNA-library suppressor screen for
      Tp53 allele-specific escape from Tp53-induced arrest was performed. Several novel
      RNAi suppressors of Tp53 were identified, one of which, PRDM1beta (BLIMP-1), was
      confirmed to be an Arg-specific transcript. Prdm1beta silences target genes by
      recruiting H3K9 trimethyl (H3K9me3) repressive chromatin marks, and is necessary
      for stem cell differentiation. These results reveal a novel model for African
      American cancer disparity, in which the TP53 codon 72 allele influences lifetime
      cancer risk by driving damaged cells to differentiation through an epigenetic
      mechanism involving gene silencing. IMPLICATIONS: TP53 P72R polymorphism
      significantly contributes to increased African American cancer disparity.

PMID- 24743657
TI  - The MATS-1 Risk Assessment Scale: Summary of Methodological Concerns and an
      Empirical Validation.
AB  - Recently, Wollert and colleagues proposed that sex offender recidivism estimates
      should be stratified by age and they developed an age-stratified scale called the
      MATS-1 (Multisample Age-Stratified Table of Sexual Recidivism). The purpose of
      this article is to highlight concerns with the development of the MATS-1 and to
      validate the scale using 3,510 sex offenders from 14 unique samples. Concerns
      with the scale's development fall into three categories: approximations leading
      to considerable loss of precision, absence of appropriate statistical tests, and
      the use of inappropriate statistical techniques. The predictive accuracy of the
      MATS-1 (Area Under the Curve [AUC] = .663) was significantly lower than Static
      99R (AUC = .708). The MATS-1 also significantly underestimated recidivism for
      some offenders. Both the relative and absolute predictive properties of the MATS
      1 were not stable across samples. We conclude that the MATS-1 is not appropriate
      to use for applied risk assessment. Proposals are made for alternate ways to
      develop risk scales using the age-stratification method. 

PMID- 24743656
TI  - Identification of candidate genes associated with positive and negative heterosis
      in rice.
AB  - To identify the genes responsible for yield related traits, and heterosis,
      massively parallel signature sequencing (MPSS) libraries were constructed from
      leaves, roots and meristem tissues from the two parents, 'Nipponbare' and '93
      11', and their F1 hybrid. From the MPSS libraries, 1-3 million signatures were
      obtained. Using cluster analysis, commonly and specifically expressed genes in
      the parents and their F1 hybrid were identified. To understand heterosis in the
      F1 hybrid, the differentially expressed genes in the F1 hybrid were mapped to
      yield related quantitative trait loci (QTL) regions using a linkage map
      constructed from 131 polymorphic simple sequence repeat markers with 266
      recombinant inbred lines derived from a cross between Nipponbare and 93-11. QTLs
      were identified for yield related traits including days to heading, plant height,
      plant type, number of tillers, main panicle length, number of primary branches
      per main panicle, number of kernels per main panicle, total kernel weight per
      main panicle, 1000 grain weight and total grain yield per plant. Seventy one QTLs
      for these traits were mapped, of which 3 QTLs were novel. Many highly expressed
      chromatin-related genes in the F1 hybrid encoding histone demethylases, histone
      deacetylases, argonaute-like proteins and polycomb proteins were located in these
      yield QTL regions. A total of 336 highly expressed transcription factor (TF)
      genes belonging to 50 TF families were identified in the yield QTL intervals.
      These findings provide the starting genomic materials to elucidate the molecular
      basis of yield related traits and heterosis in rice. 

PMID- 24743659
TI  - Strategies for reducing health disparities - selected CDC-sponsored
      interventions, United States, 2014. Foreword.

PMID- 24743658
TI  - Ten-year trends in coronary calcification in individuals without clinical
      cardiovascular disease in the multi-ethnic study of atherosclerosis.
AB  - BACKGROUND: Coronary heart disease (CHD) incidence has declined significantly in
      the US, as have levels of major coronary risk factors, including LDL-cholesterol,
      hypertension and smoking, but whether trends in subclinical atherosclerosis
      mirror these trends is not known. METHODS AND FINDINGS: To describe recent
      secular trends in subclinical atherosclerosis as measured by serial evaluations
      of coronary artery calcification (CAC) prevalence in a population over 10 years,
      we measured CAC using computed tomography (CT) and CHD risk factors in five
      serial cross-sectional samples of men and women from four race/ethnic groups,
      aged 55-84 and without clinical cardiovascular disease, who were members of Multi
      Ethnic Study of Atherosclerosis (MESA) cohort from 2000 to 2012. Sample sizes
      ranged from 1062 to 4837. After adjusting for age, gender, and CT scanner, the
      prevalence of CAC increased across exams among African Americans, whose
      prevalence of CAC was 52.4% in 2000-02, 50.4% in 2003-04, 60.0% is 2005-06, 57.4%
      in 2007-08, and 61.3% in 2010-12 (p for trend <0.001). The trend was strongest
      among African Americans aged 55-64 [prevalence ratio for 2010-12 vs. 2000-02,
      1.59 (95% confidence interval 1.06, 2.39); p = 0.005 for trend across exams].
      There were no consistent trends in any other ethnic group. Risk factors generally
      improved in the cohort, and adjustment for risk factors did not change trends in
      CAC prevalence. CONCLUSIONS: There was a significant secular trend towards
      increased prevalence of CAC over 10 years among African Americans and no change
      in three other ethnic groups. Trends did not reflect concurrent general
      improvement in risk factors. The trend towards a higher prevalence of CAC in
      African Americans suggests that CHD risk in this population is not improving
      relative to other groups.

PMID- 24743660
TI  - Background and rationale.
AB  - In 2011, CDC published the first CDC Health Disparities and Inequalities Report
      (CHDIR). This report examined health disparities in the United States associated
      with various characteristics, including race/ethnicity, sex, income, education,
      disability status, and geography. Health disparities were defined as "differences
      in health outcomes and their determinants between segments of the population, as
      defined by social, demographic, environmental, and geographic attributes". Among
      other recommendations, the 2011 CHDIR emphasized the need to address health
      disparities with a dual intervention strategy that focuses on populations at
      greatest need and improves the health of the general population by making
      interventions available to everyone. The 2013 CHDIR included updates on most
      topics from the 2011 CHDIR and on new topics. Compared with the 2011 CHDIR, the
      2013 CHDIR included more reports on social and environmental determinants of
      health and emphasizes the importance of multisector collaboration. The 2013 CHDIR
      highlights the need for a "comprehensive, community-driven approach" to reducing
      health disparities in the United States. 

PMID- 24743661
TI  - Reduction of racial/ethnic disparities in vaccination coverage, 1995-2011.
AB  - The Presidential Childhood Immunization Initiative was developed in 1993 to
      address major gaps in childhood vaccination coverage in the United States.
      Eliminating the cost of vaccines as a barrier to vaccination was one strategy of
      the Childhood Immunization Initiative; it led to Congressional legislation that
      authorized creation of the Vaccines for Children program (VFC) in 1994. CDC
      analyzed National Immunization Survey data for 1995-2011 to evaluate trends in
      disparities in vaccination coverage rates between non-Hispanic white children and
      children of other racial/ethnic groups. VFC has been effective in ireducing
      disparities in vaccination coverage among U.S. children. CDC's Office of Minority
      Health and Health Equity selected the intervention analysis and discussion that
      follows to provide an example of a program that has been effective in reducing
      childhood vaccination coverage-related disparities in the United States. At its
      inception in 1994, VFC was implemented in 78 Immunization Action Plan areas that
      covered the entire United States; within each area, concerted efforts were made
      to improve childhood vaccination coverage. The findings in this report
      demonstrate that there have been no racial/ethnic disparities in vaccine coverage
      for measles-mumps-rubella and poliovirus in the United States since 2005.
      Disparities in coverage for the diphtheria-tetanus-pertussis/diphtheria-tetanus
      acellular pertussis vaccine were absent, declining, or inconsistent during this
      period, depending on the racial/ethnic group examined. The results in this report
      highlight the effectiveness of VFC. 

PMID- 24743662
TI  - Community-based program to prevent HIV/STD infection among heterosexual black
      women.
AB  - Heterosexual non-Hispanic black women in the United States are far more affected
      than women of other races or ethnicities by human immunodeficiency virus (HIV).
      SisterLove, Inc., a community-based organization in Atlanta, Georgia, responded
      to this disparity early in the epidemic by creating the Healthy Love HIV and
      sexually transmitted disease (STD) prevention intervention in 1989. Since then,
      SisterLove has been delivering the intervention to black women in metropolitan
      Atlanta. This report describes successful efforts by SisterLove, Inc., to
      develop, rigorously evaluate, and demonstrate the efficacy of Healthy Love, a 3-4
      hour interactive, educational workshop, to reduce HIV- and sexually transmitted
      disease-related risk behaviors among heterosexual black women. On the basis of
      the evaluation findings, CDC packaged the intervention materials for use by
      service provider organizations in their efforts to reduce HIV disparities that
      affect black women in metropolitan Atlanta, the South, and the United States.
      This report also describes initiatives by SisterLove after the efficacy study to
      increase the potential effectiveness and reach of the Healthy Love intervention
      and further address HIV-related disparities that affect black women. CDC's Office
      of Minority Health and Health Equity selected the intervention analysis and
      discussion that follows to provide an example of a program that might be
      effective in reducing HIV-related disparities in the United States. The results
      of the randomized controlled efficacy trial highlight the potential of culturally
      tailored, interactive group intervention efforts to reduce health disparities.
      CDC's support for evaluating and packaging SisterLove's intervention materials,
      and making the materials available (www.effectiveinterventions.org) for use by
      service provider organizations, are important contributions toward efforts to
      address HIV-related disparities that affect black women. 

PMID- 24743663
TI  - Evidence-based HIV/STD prevention intervention for black men who have sex with
      men.
AB  - This report summarizes published findings of a community-based organization in
      New York City that evaluated and demonstrated the efficacy of the Many Men, Many
      Voices (3MV) human immunodeficiency virus (HIV)/sexually transmitted disease
      (STD) prevention intervention in reducing sexual risk behaviors and increasing
      protective behaviors among black men who have sex with men (MSM). The
      intervention addressed social determinants of health (e.g., stigma,
      discrimination, and homophobia) that can influence the health and well-being of
      black MSM at high risk for HIV infection. This report also highlights efforts by
      CDC to disseminate this evidence-based behavioral intervention throughout the
      United States. CDC's Office of Minority Health and Health Equity selected the
      intervention analysis and discussion to provide an example of a program that
      might be effective for reducing HIV infection- and STD-related disparities in the
      United States. 3MV uses small group education and interaction to increase
      knowledge and change attitudes and behaviors related to HIV/STD risk among black
      MSM. Since its dissemination by CDC in 2004, 3MV has been used in many settings,
      including health department- and community-based organization programs. The 3MV
      intervention is an important component of a comprehensive HIV and STD prevention
      portfolio for at-risk black MSM. As CDC continues to support HIV prevention
      programming consistent with the National HIV/AIDS Strategy and its high-impact
      HIV prevention approach, 3MV will remain an important tool for addressing the
      needs of black MSM at high risk for HIV infection and other STDs. 

PMID- 24743664
TI  - Tribal motor vehicle injury prevention programs for reducing disparities in motor
      vehicle-related injuries.
AB  - A previous analysis of National Vital Statistics System data for 2003-2007 that
      examined disparities in rates of motor vehicle-related death by race/ethnicity
      and sex found that death rates for American Indians/Alaska Natives were two to
      four times the rates of other races/ethnicities. To address the disparity in
      motor vehicle-related injuries and deaths among American Indians/Alaska Natives,
      CDC funded four American Indian tribes during 2004-2009 to tailor, implement, and
      evaluate evidence-based road safety interventions. During the implementation of
      these four motor vehicle-related injury prevention pilot programs, seat belt and
      child safety seat use increased and alcohol-impaired driving decreased. Four
      American Indian/Alaska Native tribal communities-the Tohono O'odham Nation, the
      Ho-Chunk Nation, the White Mountain Apache Tribe, and the San Carlos Apache Tribe
      implemented evidence-based road safety interventions to reduce motor vehicle
      related injuries and deaths. Each community selected interventions from the Guide
      to Community Preventive Services and implemented them during 2004-2009.
      Furthermore, each community took a multifaceted approach by incorporating several
      strategies, such as school and community education programs, media campaigns, and
      collaborations with law enforcement officers into their programs. Police data and
      direct observational surveys were the main data sources used to assess results of
      the programs. Results included increased use of seat belts and child safety
      seats, increased enforcement of alcohol-impaired driving laws, and decreased
      motor vehicle crashes involving injuries or deaths. CDC's Office of Minority
      Health and Health Equity selected the intervention analysis and discussion as an
      example of a program that might be effective for reducing motor vehicle-related
      injury disparities in the United States. The Guide to Community Preventive
      Services recognizes these selected interventions as effective; this report
      examines the feasibility and transferability for implementing the interventions
      in American Indian/Alaska Native tribal communities. The findings in this report
      underscore the effectiveness of community interventions to reduce motor vehicle
      crashes among selected American Indian/Alaska Native communities. 

PMID- 24743665
TI  - Decreased smoking disparities among Vietnamese and Cambodian communities - Racial
      and Ethnic Approaches to Community Health (REACH) project, 2002-2006.
AB  - Since 1964, smoking prevalence in the United States has declined because of
      nationwide intervention efforts. However, smoking interventions have not been
      implemented uniformly throughout all communities. Some of the highest smoking
      rates in the United States have been reported among Southeast Asian men, and
      socioeconomic status has been strongly associated with smoking. To compare the
      effect in reducing racial and ethnic disparities between men in Southeast Asian
      (Vietnamese and Cambodian) communities and men residing in the same states, CDC
      analyzed 2002-2006 data from The Racial and Ethnic Approaches to Community Health
      (REACH) project. The prevalence of current smoking significantly decreased and
      the quit ratio (percentage of ever smokers who have quit) significantly increased
      in REACH Vietnamese and Cambodian communities, but changes were minimal among all
      men in California or all men in Massachusetts (where these communities were
      located). The smoking rate also declined significantly, and the quit ratio showed
      an upward trend in U.S. men overall; however, the changes were significantly
      greater in REACH communities than in the nation. Stratified analyses showed
      decreasing trends of smoking and increasing trends of quit ratio in persons of
      both high and low education levels in Vietnamese REACH communities. The relative
      disparities in the prevalence of smoking and in the quit ratio decreased or were
      eliminated between less educated Vietnamese and less educated California men and
      between Cambodian and Massachusetts men regardless of education level.
      Eliminating health disparities related to tobacco use is a major public health
      challenge facing Asian communities. The decline in smoking prevalence at the
      population level in the three REACH Vietnamese and Cambodian communities as
      described in this report might serve as a model for promising interventions in
      these populations. The results highlight the potential effectiveness of community
      level interventions, such as forming community coalitions, use of local media,
      and enhancing communities' capacity for systems change. The Office of Minority
      Health and Health Equity selected this intervention analysis and discussion to
      provide an example of a program that might be effective for reducing tobacco use
      related health disparities in the United States. 

PMID- 24743666
TI  - Epilogue.
AB  - As racial and ethnic minorities constitute ever larger percentages of the U.S.
      population, the overall health statistics of the nation increasingly reflect the
      health status of these groups. Overcoming persistent health and health-care
      disparities that affect racial/ethnic minorities benefits the entire society. For
      example, the economic well-being of a nation relies on the health of its
      populace. According to one report, "The nation's dependence on an increasingly
      minority workforce means that healthy communities of color are vital to the
      nation's economic fortunes". Other U.S. population groups, such as persons with
      disabilities or special health-care needs, persons living in certain geographic
      locations, and persons with certain sexual identities or sexual orientations,
      also have higher rates of preventable morbidity and premature death, and efforts
      should be directed toward improving their health outcomes and eliminating health
      disparities. 

PMID- 24743667
TI  - Laparoscopic ventral hernia repair: defining the learning curve.
AB  - Between 2004 and June 2011, 181 patients underwent laparoscopic ventral hernia
      repair. Three main surgeons, all experienced in laparoscopic procedures,
      performed all the cases. After analyzing the operative time (OT) for 3 main
      surgeons, within the first 20 cases the overall performance plateaued. Data from
      60 patients (50F, 10M), with a mean age of 42.3 years (range, 26 to 88 y) and a
      mean hernia defect size of 6.5 cm (range, 4 to 18 y), were evaluated. No
      significant differences were recorded among the 3 surgeons in OT and
      intraoperative or postoperative complications. But 3 (5%, P<0.03) patients had
      complications, and the recurrence rate was 6.6% with a mean follow-up of 54
      months (range, 42 to 70 mo). One had prolonged postoperative ileus, the second
      had bowel serosal tear, and the last had port-site incarcerated hernia. Our
      results showed that the OT of 98.9 minutes (range, 48 to 205 min) stabilized in
      12 cases. 

PMID- 24743668
TI  - Long-term quality of life in gastroesophageal reflux disease after NISSEN
      fundoplication: does it depend on preoperative responsiveness to proton pump
      inhibitors?
AB  - PURPOSE: In patients presenting with uncomplicated gastroesophageal reflux
      disease, nonresponders to medical treatment are not viewed as good candidates for
      surgical treatment. Considering preoperative response to medical treatment and
      quality of life, this study aimed to predict outcome following laparoscopic
      Nissen fundoplication. MATERIALS AND METHODS: In an academic center, 35
      consecutive patients presenting with a gastroesophageal reflux disease requiring
      a laparoscopic Nissen fundoplication were prospectively included; 16 patients
      were nonresponders. Using Gastro-Intestinal Quality-of-Life Index score, quality
      of life was measured preoperatively and postoperatively at each visit (3, 6, 12,
      24, 48, and 72 mo) and was compared between responders and nonresponders.
      RESULTS: No postoperative complication was recorded. Preoperative score was
      significantly lower in nonresponders (P<0.02) and digestive symptoms and dietary
      modifications were more important in nonresponders. The score increased in
      nonresponders after 48 and 72 months, but this improvement was nonsignificantly
      lower than in responders (P=0.4). In nonresponders, 6 years after the procedure,
      all symptoms improved. In responders, dysphagia and gastroesophageal reflux
      symptoms significantly improved. CONCLUSIONS: Laparoscopic Nissen fundoplication
      seems to improve the quality of life in nonresponders without equaling to
      responders results, especially because of digestive symptoms. Laparoscopic Nissen
      fundoplication may be considered as a therapeutic option in selected and informed
      nonresponder patients.

PMID- 24743669
TI  - Clinical outcomes and quality of life according to types of reconstruction
      following laparoscopy-assisted distal gastrectomy for gastric cancer.
AB  - PURPOSES: Laparoscopy-assisted distal gastrectomy (LADG) has gained wide
      acceptance and is being more commonly performed at the period of introduction.
      This study was designed to determine the clinical outcomes and quality of life
      (QOL) according to types of reconstruction following LADG for gastric cancer.
      PATIENTS AND METHODS: Between 2007 and 2010, 117 consecutive patients underwent
      LADG. These patients were classified into 2 groups: Billroth-I group (n=74) and
      Roux-en-Y group (n=48). RESULTS: Although there were no significant differences
      in background factors such as sex, body mass index, pN stage, pT stage, or extent
      of lymphadenectomy between both the groups, patients with Billroth-I
      reconstruction were found more frequently in the lower portion of gastric cancer
      (P=0.0173), shorter surgical durations (P<0.0001), and less blood loss
      (P<0.0001). The overall postoperative complication rates did not significantly
      differ between both the groups (P=0.0675). However, the incidence of patients
      with postoperative stasis (P=0.0170) and long hospital stay (P=0.0039) was
      significantly higher in patients with Roux-en-Y reconstruction. Concerning the
      evaluation of long-term QOL using the Gastrointestinal Symptom Rating Scale,
      there were no significant differences in total score between both the groups
      (P=0.4387). CONCLUSIONS: Billroth-I technique might comparatively be accessible
      and safe in the reconstruction of LADG. However, the differences of
      reconstruction do not affect long-term QOL.

PMID- 24743670
TI  - Single-incision laparoscopic surgery through an ostomy site: a natural approach
      by an unnatural orifice.
AB  - Single-incision laparoscopic surgery (SILS) is gaining popularity for a wide
      variety of surgical operations and capitalizes on the benefits of traditional
      laparoscopic surgery without incurring multiple incision sites. Traditionally,
      SILS is performed by a midline periumbilical approach. However, such a minimally
      invasive approach may be utilized in patients who already have an abdominal
      incision. Our series retrospectively reviews 7 cases in which we utilized the
      fascial defect at the time of after ostomy reversal as our SILS incision site. In
      turn, we performed a variety of concurrent intra-abdominal procedures with
      excellent technical success and outcomes. Our study is the largest single
      institution case series of this novel approach and suggests that utilizing an
      existing ostomy-site abdominal incision is a safe and effective location for SILS
      port placement and should be considered in patients undergoing concurrent
      procedures. 

PMID- 24743671
TI  - Closed-tube thoracostomy: a novel emergency surgery technique.
AB  - BACKGROUND: The practice of tube thoracostomy entails high risk as it is a closed
      technique. Open thoracostomy and closed minithoracostomy techniques have been
      approved worldwide as safe modalities. Applying the concept of a new closed
      thoracostomy technique with high safety and simplicity is a major advancement in
      this regard. MATERIALS AND METHODS: This was a case series pilot study
      introducing a new technique for closed-tube thoracostomy. Thirty-one patients
      with primary unilateral pneumothorax were selected for the study. All patients
      coming to the Emergency Department at Security Forces Hospital, Dammam City,
      Kingdom of Saudi Arabia, between January and August 2012, matching the study
      criteria were recruited to undergo the new technique. The surgical set required
      for the technique was defined and prepared sterile. Preinsertion and
      postinsertion chest x-ray and chest computed tomography scans were obtained for
      the entire study sample. RESULTS: We recruited the first 31 patients requiring
      tube thoracostomy who visited the Emergency Department. All procedures were
      performed by the author, assisted by on-call registrars. No complications were
      observed with the new technique. Moreover, advantages of the technique were
      demonstrated and documented. CONCLUSIONS: The new technique provides safe tube
      introduction and precise tube positioning, saves time, and involves no technical
      precautions. The technique has been applied on selected simple cases as the first
      trial and requires further testing in cases of hemothorax, empyema thoracis,
      traumatic chest injuries, and complicated pulmonary diseases that require
      drainage. Further evaluation of the technique by randomized studies is required.

PMID- 24743672
TI  - Laparoscopic distal pancreatectomy for solid-pseudopapillary tumor of the
      pancreas.
AB  - PURPOSE: Solid-pseudopapillary tumor (SPT) of pancreas is a rare entity with a
      low malignant potential. We aimed to identify the safety and the feasibility of
      laparoscopic distal pancreatectomy for SPT. METHODS: From May 2008 to August
      2011, we performed 4 cases of laparoscopic, spleen-preserving, distal
      pancreatectomies for patients with SPT. We retrospectively collected the
      demographic characteristics, operative and postoperative details, and follow-up
      outcomes of the patients. RESULTS: Three female patients and 1 male patient with
      SPT underwent laparoscopic, spleen-preserving, distal pancreatectomy. The average
      operating time was 200 minutes. The average blood loss was 90 mL. The
      postoperative course of these patients was uneventful. All patients were followed
      up and no local recurrence or metastasis was found. CONCLUSIONS: Laparoscopic
      distal pancreatectomy for patients with SPT is safe and feasible, with preferable
      operative outcomes, long-term tumor-free survival, and high spleen-preserving
      rate.

PMID- 24743673
TI  - A novel technique of needle-guided laparoscopic enucleation of insulinomas.
AB  - Insulinomas are rare, usually benign and solitary neuroendocrine tumors that
      cause oversecretion of insulin. Surgical excision remains the only treatment
      modality with the potential for cure. Compared to open extensive pancreatic
      resections, laparoscopic enucleation of these tumors offers effective treatment,
      and significantly reduced risks of complications. However, accurate tumor
      localization is extremely important, especially in cases of lesions deep seated
      into the head of the pancreas. We present here a novel technique of
      intraoperative localization of lesions that are not visible on the surface of
      pancreas. Using laparoscopic intraoperative ultrasound, tumors were located in
      the parenchyma of the pancreatic head and then an 18-G needle was inserted into
      the pancreatic lesion intraoperatively under laparoscopic sonographic guidance.
      The pancreatic parenchyma was then divided until the dome of tumor was visible,
      minimizing tissue trauma, and enucleation was performed. This technique is a
      useful tool that substantially improves the chances of successful laparoscopic
      enucleation of deep-seated small pancreatic insulinomas. 

PMID- 24743674
TI  - Evaluating informed consent for colonoscopy.
AB  - BACKGROUND: This study aimed to collect and analyze data on patient knowledge of
      colonoscopy and their preferences regarding the provision of information about
      the procedure. Specifically, how much detail patients know about different
      aspects of the procedure and through which methods they best understand risk are
      evaluated and demographic correlations identified. MATERIALS AND METHODS: The
      study sample consisted of colonoscopy patients from 2 colorectal surgeons and a
      gastroenterologist at St Vincent's Public Hospital, Sydney for the period August
      1 to November 1, 2010. A voluntary questionnaire was performed in the waiting
      room before colonoscopy. The questionnaire collected data on patient
      demographics; patient-perceived knowledge of the procedure; and understanding and
      preferences of various communication formats. RESULTS: Measures of patient
      perceived knowledge about colonoscopy were significantly lower than those that
      would be preferred by patients (P=0.002). Those with higher levels of education
      preferred communication of colonoscopy-related information via a leaflet form,
      whereas those with lower levels preferred verbal information from a doctor or
      nurse (P=0.049). The most preferred format for explaining the risk of perforation
      was the pie graph, followed by both the 1000-person pictograph and absolute risk
      ratios. CONCLUSIONS: Patients received suboptimal levels of information about
      colonoscopy compared with their preferences. Key areas for improvement include
      providing more understandable information about the risks of colonoscopy. A
      combination of written information, diagrams and graphs, and then a discussion of
      this information to check the understanding is likely to be most effective.
      Further research into the communication of risk, with larger groups of patients,
      is likely to help clinicians in gaining fully informed consent in all patients.

PMID- 24743675
TI  - Prospective evaluation of crural repair with and without double-sided mesh
      reinforcement.
AB  - BACKGROUND: Laparoscopic Nissen fundoplication is gold standard treatment for
      gastroesophageal reflux disease. We examined the results of laparoscopic Nissen
      fundoplication with or without double-sided polypropylene mesh. PATIENTS AND
      METHODS: Sixty patients were prospectively evaluated. Primer cruroraphy and
      primer cruroraphy with mesh were performed in 31 and 29 patients, respectively.
      The Gastrointestinal Quality of Life Index (GIQLI) was used for assessment of the
      patient satisfaction preoperatively and postoperatively at 12 months. RESULTS:
      Sixty patients were included in the study, with a mean age of 42 years. There was
      no difference between the 2 groups with respect to age, sex, and duration of
      symptoms. GIQLI showed an equal improvement, and there were no differences in the
      quality of life in both the groups. All patients' endoscopic findings were normal
      at first year. CONCLUSIONS: Laparoscopic Nissen fundoplication appears to prevent
      reflux and its symptoms and create better quality of life. Double-sided
      polypropylene mesh for repair may result in better quality of life.

PMID- 24743676
TI  - New transjugular retrograde obliteration without the use of ethanolamine oleate
      for gastric varices.
AB  - OBJECTIVES: The purpose of this study was to investigate the short-term effects
      of new transjugular retrograde obliteration (TJO) without the use of ethanolamine
      oleate for gastric varices with a gastrorenal shunt. PATIENTS AND METHODS: Ten
      patients with gastric varices and a gastrorenal shunt were included in this
      study. Through the right internal jugular vein, a 5- or 6-Fr angiographic
      catheter with an occlusive balloon was inserted into the gastrorenal shunt. The
      balloon was inflated to occlude the gastrorenal shunt blood flow. Microcoils were
      used to obliterate the main blood drainage routes of gastric vein, such as
      inferior phrenic and and/or retroperitoneal veins. Continuous injection of 0.5 to
      1.0 mL of absolute ethanol and 2 to 15 mL of 50% glucose solution into the
      gastrorenal shunt was carried out under fluoroscopy. This procedure was repeated
      at 5-minute intervals until gastric varices were clearly visualized. 5%
      ethanolamine oleate with iopamidol (5% EOI) was not used as a sclerosant.
      RESULTS: TJO without 5% EOI technically succeeded in all cases. Total volumes of
      absolute ethanol and 50% glucose solution for the variceal obliteration were 6+/
      4 and 56+/-46 mL, respectively. To produce thrombi in the gastric varices, the
      catheter had to be retained for 24 hours in 7 patients and for 48 hours in 3. The
      volumes of absolute ethanol and 50% glucose solution were 4+/-2 and 37+/-20 in
      the former 7 patients and 11+/-4 and 100+/-64 mL in the latter 3 patients,
      respectively. Only minor complications were observed, which were as follows:
      fever >38 degrees C in 6 patients, epigastric pain in 8 patients, and temporary
      hypertension in 2 patients. Computed tomography scan and endoscopic examination 3
      months after TJO revealed complete eradication of gastric varices in all cases.
      CONCLUSIONS: We conclude that new TJO without the use of 5% EOI is an effective
      and safe method for gastric varices.

PMID- 24743677
TI  - Laparoscopy versus open distal gastrectomy for advanced gastric cancer: a
      systematic review and meta-analysis (Qiu J et al. Surg Laparosc Endosc Percutan
      Tech 2013;23:1-7).

PMID- 24743678
TI  - Minimally invasive surgical approach compared with open pancreaticoduodenectomy:
      a systematic review and meta-analysis on the feasibility and safety.
AB  - BACKGROUND: Laparoscopic and robotic pancreaticoduodenectomy have started
      utilization tentatively; however, the clinical benefits are still controversial.
      This study aims to evaluate the safety and efficiency of minimally invasive
      pancreaticoduodenectomy. METHODS: A systematic literature search was performed
      through PubMed, EMBASE, and Cochrane Library database without restriction to
      regions, publication types, or languages. Nine studies that compared
      laparoscopic/robotic with open pancreaticoduodenectomy were included. Fixed or
      random-effects models was used to measure the pooled estimates. Sensitivity and
      subgroup analysis were performed to evaluate the study quality. RESULTS: Patients
      who underwent minimally invasive pancreaticoduodenectomy experienced longer
      operative time (P=0.007), but the estimated blood loss (P=0.007), length of stay,
      (P=0.02), and wound infection (P=0.04) decreased. Perioperative complications,
      such as pancreatic fistula, delayed gastric emptying, hemorrhage, bile leakage,
      reoperation, and mortality, were of no significant differences. Pathologically,
      lymph node number was similar (P=0.11); meanwhile, margin R0 ratio was higher in
      minimally invasive approach group (P=0.03). Subgroup analysis manifested robotic
      surgery spent comparable surgical time (P=0.16) as laparotomy, with earlier
      discharge (P=0.04). CONCLUSIONS: This meta-analysis indicates minimally invasive
      pancreaticoduodenectomy may be associated with shorter hospital stay, less
      estimated blood loss, and positive margin rate without compromising surgical
      safety as open surgery. Surgical duration of robotic method could even be
      equivalent as laparotomy. Minimally invasive approach can be a reasonable
      alternative to laparotomy pancreaticoduodenectomy with potential advantages.
      Nevertheless, future large-volume, well-designed RCTs with extensive follow-up
      are awaited to confirm and update the findings of this analysis.

PMID- 24743679
TI  - Compressive hematoma due to pseudoaneurysm of the right hepatic artery: a rare
      cause of obstructive jaundice after single-port cholecystectomy.
AB  - Single-port laparoscopic cholecystectomy is considered as a form of natural
      orifice surgery with better esthetic outcomes than traditional laparoscopic
      cholecystectomy. It is a technically demanding procedure, and no adequately
      powered trial has assessed the safety of this technique. Vascular injuries are
      less common than bile duct injuries during this procedure, but they can be
      rapidly fatal. The development of a right hepatic artery pseudoaneurysm is a rare
      but serious complication associated with single-port laparoscopic
      cholecystectomy. Two weeks following a single-port laparoscopic cholecystectomy
      for angiocholitis, a 40-year-old male patient presented with obstructive jaundice
      and persistent abdominal pain. The diagnosis of compressive hematoma due to a
      ruptured right hepatic artery pseudoaneurysm was confirmed by computed tomography
      scan and angiography. It was successfully treated by selective embolization of
      the right hepatic artery. In our experience, endovascular management was a
      noninvasive and effective treatment of ruptured pseudoaneurysms. 

PMID- 24743680
TI  - Laparoscopic approach for liver hydatid cyst: primum no nocer.

PMID- 24743681
TI  - Radiofrequency ablation of treatment-refractory gastric antral vascular ectasia
      (GAVE).
AB  - Gastric antral vascular ectasia (GAVE) is a rare but an important cause of
      gastrointestinal bleeding and anemia. Endoscopic ablation is usually successful,
      but treatment-refractory cases occur. We have used radiofrequency ablation (RFA)
      with the HALO device in these cases with positive results. Nine patients (5
      female patients) with refractory GAVE were treated with RFA. Four had GAVE
      associated with cirrhosis, 4 had renal insufficiency, and 1 had both cirrhosis
      and renal insufficiency. Patients had received multiple endoscopic treatments
      before undergoing RFA over a period of up to 2 years (median 4; range, 2 to 15
      y). A total of 2 to 6 (median 3) RFA sessions were performed until GAVE
      eradication. Endoscopic ablation was achievable in all patients. There were no
      complications of the treatments. Seven of the 9 patients had sustained response
      to RFA over a median follow-up of 11 months (range, 6 to 21 mo). 

PMID- 24743682
TI  - Wikipedia usage estimates prevalence of influenza-like illness in the United
      States in near real-time.
AB  - Circulating levels of both seasonal and pandemic influenza require constant
      surveillance to ensure the health and safety of the population. While up-to-date
      information is critical, traditional surveillance systems can have data
      availability lags of up to two weeks. We introduce a novel method of estimating,
      in near-real time, the level of influenza-like illness (ILI) in the United States
      (US) by monitoring the rate of particular Wikipedia article views on a daily
      basis. We calculated the number of times certain influenza- or health-related
      Wikipedia articles were accessed each day between December 2007 and August 2013
      and compared these data to official ILI activity levels provided by the Centers
      for Disease Control and Prevention (CDC). We developed a Poisson model that
      accurately estimates the level of ILI activity in the American population, up to
      two weeks ahead of the CDC, with an absolute average difference between the two
      estimates of just 0.27% over 294 weeks of data. Wikipedia-derived ILI models
      performed well through both abnormally high media coverage events (such as during
      the 2009 H1N1 pandemic) as well as unusually severe influenza seasons (such as
      the 2012-2013 influenza season). Wikipedia usage accurately estimated the week of
      peak ILI activity 17% more often than Google Flu Trends data and was often more
      accurate in its measure of ILI intensity. With further study, this method could
      potentially be implemented for continuous monitoring of ILI activity in the US
      and to provide support for traditional influenza surveillance tools. 

PMID- 24743683
TI  - Characteristics of harmonic indexes of the arterial blood pressure waveform in
      polycystic ovary syndrome.
AB  - MOTIVATIONS: Patients with polycystic ovary syndrome (PCOS; which is often
      associated with increased cardiovascular risk factors) may present hemodynamic
      changes in the cardiovascular system. The aim of the present study was to verify
      whether harmonic indexes of the arterial blood pressure waveform (BPWs) can be
      used to discriminate between PCOS patients and healthy individuals. METHODS:
      Twenty-minute bilateral radial BPW signals were obtained in 20 PCOS patients and
      20 healthy individuals. Amplitude proportions (Cn values) and their coefficients
      of variation (CVn values) were calculated for harmonics 1-10 of the BPW. RESULTS:
      C1 was significantly larger whereas C4, CV2, and CV6 were significantly smaller
      in PCOS patients compared with healthy individuals. DISCUSSION: The results of
      the present study suggest that harmonic-analysis indexes of the BPWs could
      provide information about the arterial pulse transmission (by monitoring Cn) and
      cardiovascular regulatory activities (by monitoring CVn). These findings could
      aid the development of an easy-to-perform, noninvasive, and continuous monitoring
      technique to improve the detection of PCOS-induced hemodynamic changes.

PMID- 24743684
TI  - The appraisal of chronic stress and the development of the metabolic syndrome: a
      systematic review of prospective cohort studies.
AB  - Chronic psychosocial stress has been proposed as a risk factor for the
      development of the metabolic syndrome (MES). This review gives a systematic
      overview of prospective cohort studies investigating chronic psychosocial stress
      as a risk factor for incident MES and the individual elements of MES. Thirty-nine
      studies were included. An association between chronic psychosocial stress and the
      development of MES was generally supported. Regarding the four elements of MES:
      i) weight gain: the prospective studies supported etiological roles for
      relationship stress, perceived stress, and distress, while the studies on work
      related stress (WS) showed conflicting results; ii) dyslipidemi: too few studies
      on psychosocial stress as a risk factor for dyslipidemia were available to draw a
      conclusion; however, a trend toward a positive association was present; iii) type
      2 diabetes mellitus (DM2): prospective studies supported perceived stress and
      distress as risk factors for the development of DM2 among men, but not among
      women, while WS was generally not supported as a risk factor among neither men
      nor women; iv) hypertension: marital stress and perceived stress might have an
      influence on blood pressure (BP), while no association was found regarding
      distress. Evaluating WS the results were equivocal and indicated that different
      types of WS affected the BP differently between men and women. In conclusion, a
      longitudinal association between chronic psychosocial stress and the development
      of MES seems present. However, the number of studies with sufficient quality is
      limited and the design of the studies is substantially heterogeneous. 

PMID- 24743685
TI  - Genetic variants in FBN-1 and risk for thoracic aortic aneurysm and dissection.
AB  - OBJECTIVES: A recent genome wide association study (GWAS) by LeMaire et al. found
      that two single nucleotide polymorphisms (SNPs), rs2118181 and rs10519177 in the
      FBN-1 gene (encoding Fibrillin-1), were associated with thoracic aortic
      dissection (TAD), non-dissecting thoracic aortic aneurysm (TAA), and thoracic
      aortic aneurysm or dissection (TAAD); the largest effect was observed for the
      association of rs2118181 with TAD. We investigated whether rs2118181 and
      rs10519177 were associated with TAD, TAA, and TAAD in the Yale study. METHODS:
      The genotypes of rs2118181 and rs10519177 were determined for participants in the
      Yale study: 637 TAAD cases (140 TAD, 497 TAA) and 275 controls from the United
      States, Hungary, and Greece. The association of the genotypes with TAD, TAA and
      TAAD were assessed using logistic regression models adjusted for sex, age, study
      center and hypertension. RESULTS AND CONCLUSIONS: In the Yale study, rs2118181
      was associated with TAD: compared with non-carriers, carriers of the risk allele
      had an unadjusted odds ratio for TAD of 1.80 (95% CI 1.15-2.80) and they had odds
      ratio for TAD of 1.87 (95% CI 1.09-3.20) after adjusting for sex, age, study
      center and hypertension. We did not find significant differences in aortic size,
      a potential confounder for TAD, between rs2118181 risk variant carriers and non
      carriers: mean aortic size was 5.56 (95% CI: 5.37-5.73) for risk variant carriers
      (CC+CT) and was 5.48 (95% CI: 5.36-5.61) for noncarriers (TT) (p = 0.56).
      rs2118181 was not associated with TAA or TAAD. rs10519177 was not associated with
      TAD, TAA, or TAAD in the Yale study. Thus, the Yale study provided further
      support for the association of the FBN-1 rs2118181SNP with TAD.

PMID- 24743686
TI  - Sleep-disordered breathing increases the risk of arrhythmias.
AB  - Sleep-disordered breathing (SDB) has been consistently associated with increased
      risk for cardiovascular diseases, including arrhythmias. The purpose of this
      review is to elucidate the several pathophysiologic pathways such as repetitive
      hypoxia and reoxygenation, increased oxidative stress, inflammation and
      sympathetic activation that may underlie the increased incidence of arrhythmias
      in SDB patients. We discuss in particular the incidence of ventricular
      arrhythmias, atrial fibrillation and bradyarrhythmias in SDB patients. In
      addition, we discuss the electrocardiographic alteration such as ST-T changes
      during apneic events and QT dispersion induced by SDB that may trigger complex
      ventricular arrhythmias and sudden cardiac death. Finally, we consider also the
      therapeutic interventions such as continuous positive airways pressure therapy, a
      standard treatment for SDB, that may reduce the incidence and recurrence of
      supraventricular and ventricular arrhythmias in patients with SDB. 

PMID- 24743687
TI  - Association of LOXIN, a new functional splicing isoform of the OLR1 gene, with
      severity and prognostic localization of critical coronary artery stenoses.
AB  - AIMS: To evaluate the association between LOXIN, a new functional protective
      splicing isoform of the oxidized LDL receptor 1 (OLR1) gene, and the severity of
      coronary artery stenoses. METHODS: We analyzed 100 consecutive patients with
      coronary artery disease (CAD) and 100 controls, all evaluated by a new molecular
      biology test using highly specific allele primers able to identify the single
      nucleotide variation (IVS4-14 A>G) in the OLR1 gene (Loxin Test -
      Technogenetics). All the patients and the controls underwent coronary angiography
      and, for quantitative evaluation, we used both vessel and stenosis score, and
      SYNTAX score to evaluate the severity of CAD. Moreover, we defined the prognostic
      localization of CAD as a critical stenosis (>50%) of the left main and/or
      proximal segment of left anterior descending artery (LAD). Finally, we evaluated
      a correlation with the presence of diabetes mellitus, dyslipidemia, hypertension,
      smoking and family history of CAD. RESULTS: In this selected population, even
      though the 'AA nonrisk haplotype' is more frequent in the controls, we did not
      find any statistically significant correlation between the severity of CAD or the
      prognostic localization of critical stenosis and the difference of IVS4-14 A>G
      OLR1 genotype (P > 0.05). CAD patients showed significantly higher frequencies of
      dyslipidemia and smoking (P < 0.05) than controls, but no significant association
      was found between overall risk factors and the OLR1 polymorphism. CONCLUSION: In
      this selected population, we did not find any correlation of LOXIN with the
      severity or prognostic localization of CAD on left main and/or proximal LAD.

PMID- 24743688
TI  - Association of butyrylcholinesterase with cardiometabolic risk factors among
      apparently healthy adults.
AB  - BACKGROUND: Although butyrylcholinesterase is widely distributed in different
      tissues of the human body, its physiological role has not yet been defined. This
      study aimed to explore the relationship between butyrylcholinesterase and lipids
      levels, among apparently healthy adults. METHODS: During 2009, 490 volunteers (46
      +/- 16 years, 40% men) who visited the outpatients' office of our hospital for
      routine examinations were consecutively enrolled in the study (participation rate
      85%). Biochemical analyses were performed through established procedures, after
      12 h fasting, and haematological as well as biochemical parameters were measured.
      Anthropometric, lifestyle and dietary characteristics were also recorded to
      account for potential confounding. RESULTS: Butyrylcholinesterase activity was
      positively correlated with glucose, low-density lipoprotein (LDL)-cholesterol,
      total cholesterol, triglycerides, uric acid, haptoglobin and platelet count,
      after age-sex adjustments (all Ps < 0.05). Further adjustment for a series of
      anthropometric, lifestyle and clinical characteristics revealed that only BMI,
      LDL-cholesterol, total cholesterol and triglycerides were positively associated
      with serum butyrylcholinesterase activity. CONCLUSIONS: This study demonstrated
      the positive association of serum butyrylcholinesterase activity with BMI, LDL
      cholesterol, total cholesterol and triglycerides, a fact that could state a
      hypothesis for a novel marker of atherosclerotic disease that could - together
      with other biomarkers - improve our potential to assess cardiovascular disease
      risk.

PMID- 24743689
TI  - Reduction of phosphorylated synapsin I (ser-553) leads to spatial memory
      impairment by attenuating GABA release after microwave exposure in Wistar rats.
AB  - BACKGROUND: Abnormal release of neurotransmitters after microwave exposure can
      cause learning and memory deficits. This study investigated the mechanism of this
      effect by exploring the potential role of phosphorylated synapsin I (p-Syn I).
      METHODS: Wistar rats, rat hippocampal synaptosomes, and differentiated (neuronal)
      PC12 cells were exposed to microwave radiation for 5 min at a mean power density
      of 30 mW/cm2. Sham group rats, synaptosomes, and cells were otherwise identically
      treated and acted as controls for all of the following post-exposure analyses.
      Spatial learning and memory in rats was assessed using the Morris Water Maze
      (MWM) navigation task. The protein expression and presynaptic distribution of p
      Syn I and neurotransmitter transporters were examined via western blotting and
      immunoelectron microscopy, respectively. Levels amino acid neurotransmitter
      release from rat hippocampal synaptosomes and PC12 cells were measured using high
      performance liquid chromatograph (HPLC) at 6 hours after exposure, with or
      without synapsin I silencing via shRNA transfection. RESULTS: In the rat
      experiments, there was a decrease in spatial memory performance after microwave
      exposure. The expression of p-Syn I (ser-553) was decreased at 3 days post
      exposure and elevated at later time points. Vesicular GABA transporter (VGAT) was
      significantly elevated after exposure. The GABA release from synaptosomes was
      attenuated and p-Syn I (ser-553) and VGAT were both enriched in small clear
      synaptic vesicles, which abnormally assembled in the presynaptic terminal after
      exposure. In the PC12 cell experiments, the expression of p-Syn I (ser-553) and
      GABA release were both attenuated at 6 hours after exposure. Both microwave
      exposure and p-Syn I silencing reduced GABA release and maximal reduction was
      found for the combination of the two, indicating a synergetic effect. CONCLUSION:
      p-Syn I (ser-553) was found to play a key role in the impaired GABA release and
      cognitive dysfunction that was induced by microwave exposure.

PMID- 24743690
TI  - Documenting the density of subtidal marine debris across multiple marine and
      coastal habitats.
AB  - Marine debris is recognised globally as a key threatening process to marine life,
      but efforts to address the issue are hampered by the lack of data for many marine
      habitats. By developing standardised protocols and providing training in their
      application, we worked with >300 volunteer divers from 11 underwater research
      groups to document the scale of the subtidal marine debris problem at 120 sites
      across >1000 km of the coast of NSW, Australia. Sampling consisted of replicated
      25*5 m transects in which all debris was identified, counted, and, where
      appropriate, removed. Sites ranged from estuarine settings adjacent to major
      population centres, to offshore islands within marine parks. Estuaries and
      embayments were consistently found to be the most contaminated habitats. Fishing
      related items (and especially monofilament and braided fishing line) were most
      prevalent at the majority of sites, although food and drink items were important
      contributors at sites adjacent to population centres. The results identified
      damaging interactions between marine debris and marine biota at some key
      locations, highlighting the need for management intervention to ensure habitat
      sustainability. This study reinforces the important contribution that volunteers
      can make to assessing conservation issues requiring broad-scale data collection.
      In this case, citizen scientists delivered data that will inform, and help to
      prioritise, management approaches at both statewide and local scales. These
      initial data also provide an important baseline for longer-term, volunteer-based
      monitoring programs. 

PMID- 24743691
TI  - Gentamicin-attenuated Leishmania infantum vaccine: protection of dogs against
      canine visceral leishmaniosis in endemic area of southeast of Iran.
AB  - An attenuated line of Leishmania infantum (L. infantum H-line) has been
      established by culturing promastigotes in vitro under gentamicin pressure. A
      vaccine trial was conducted using 103 naive dogs from a leishmaniosis non-endemic
      area (55 vaccinated and 48 unvaccinated) brought into an endemic area of
      southeast Iran. No local and/or general indications of disease were observed in
      the vaccinated dogs immediately after vaccination. The efficacy of the vaccine
      was evaluated after 24 months (4 sandfly transmission seasons) by serological,
      parasitological analyses and clinical examination. In western blot analysis of
      antibodies to L. infantum antigens, sera from 10 out of 31 (32.2%) unvaccinated
      dogs, but none of the sera from vaccinated dogs which were seropositive at >100,
      recognized the 21 kDa antigen of L. infantum wild-type (WT). Nine out of 31 (29%)
      unvaccinated dogs, but none of vaccinated dogs, were positive for the presence of
      Leishmania DNA. One out of 46 (2.2%) vaccinated dogs and 9 out of 31 (29%)
      unvaccinated dogs developed clinical signs of disease. These results suggest that
      gentamicin-attenuated L. infantum induced a significant and strong protective
      effect against canine visceral leishmaniosis in the endemic area. 

PMID- 24743692
TI  - Effect of geometric parameters on the performance of p-type junctionless lateral
      gate transistors.
AB  - This paper examines the impact of two important geometrical parameters, namely
      the thickness and source/drain extensions on the performance of low doped p-type
      double lateral gate junctionless transistors (DGJLTs). The three dimensional
      Technology Computer-Aided Design simulation is implemented to calculate the
      characteristics of the devices with different thickness and source/drain
      extension and based on that, the parameters such as threshold voltage,
      transconductance and resistance in saturation region are analyzed. In addition,
      simulation results provide a physical explanation for the variation of device
      characteristics given by the variation of geometric parameters, mainly based on
      investigation of the electric field components and the carries density variation.
      It is shown that, the variation of the carrier density is the main factor which
      affects the characteristics of the device when the device's thickness is varied.
      However, the electric field is mainly responsible for variation of the
      characteristics when the source/drain extension is changed. 

PMID- 24743693
TI  - The efficacy of landscape-level conservation in Changbai Mountain Biosphere
      Reserve, China.
AB  - Anthropogenic landscape alteration is rather common in many protected areas
      (PAs), jeopardizing the efficacy of PAs conservation. However, the general
      consensus is that PAs still remain effective in habitat conservation. To assess
      the efficacy of landscape-level conservation, we examined landscape alterations
      in the Changbai Mountain Biosphere Reserve (CMBR), which was established in 1960
      as a "flagship" protected area in China. Based on analyses of high-resolution
      satellite images and data of forest inventory, field survey and interview, we
      developed two new indexes to assess the efficacy of landscape conservation, i.e.
      the quality index of protected landscape and the interference index of
      anthropogenic landscape. From 1993 to 2012, the quality index increased from
      74.48 to 75.50, and the interference index decreased from 0.49 to 0.06,
      suggesting that the overall quality of protected landscape improved and the
      degree of anthropogenic interference decreased in CMBR. The increase in landscape
      quality was mainly due to the progressive vegetation recovery of previous cutover
      land in the windthrow area, the cease of the use of the cultivated land, and the
      amelioration of spatial pattern of protected landscape. We conclude that the
      current landscape conservation methods used in CMBR are effective, and the method
      we developed has the potential to be used to assess the efficacy of landscape
      level conservation in nature reserves worldwide. 

PMID- 24743694
TI  - Art27 interacts with GATA4, FOG2 and NKX2.5 and is a novel co-repressor of
      cardiac genes.
AB  - Transcription factors play a crucial role in regulation of cardiac biology. FOG-2
      is indispensable in this setting, predominantly functioning through a physical
      interaction with GATA-4. This study aimed to identify novel co-regulators of FOG
      2 to further elaborate on its inhibitory activity on GATA-4. The Art27
      transcription factor was identified by a yeast-2-hybrid library screen to be a
      novel FOG-2 protein partner. Characterisation revealed that Art27 is co-expressed
      with FOG-2 and GATA-4 throughout cardiac myocyte differentiation and in multiple
      structures of the adult heart. Art27 physically interacts with GATA-4, FOG-2 and
      other cardiac transcription factors and by this means, down-regulates their
      activity on cardiac specific promoters alpha-myosin heavy chain, atrial
      natriuretic peptide and B-type natriuretic peptide. Regulation of endogenous
      cardiac genes by Art27 was shown using microarray analysis of P19CL6-Mlc2v-GFP
      cardiomyocytes. Together these results suggest that Art27 is a novel
      transcription factor that is involved in downregulation of cardiac specific genes
      by physically interacting and inhibiting the activity of crucial transcriptions
      factors involved in cardiac biology. 

PMID- 24743695
TI  - Classifying different emotional states by means of EEG-based functional
      connectivity patterns.
AB  - This study aimed to classify different emotional states by means of EEG-based
      functional connectivity patterns. Forty young participants viewed film clips that
      evoked the following emotional states: neutral, positive, or negative. Three
      connectivity indices, including correlation, coherence, and phase
      synchronization, were used to estimate brain functional connectivity in EEG
      signals. Following each film clip, participants were asked to report on their
      subjective affect. The results indicated that the EEG-based functional
      connectivity change was significantly different among emotional states.
      Furthermore, the connectivity pattern was detected by pattern classification
      analysis using Quadratic Discriminant Analysis. The results indicated that the
      classification rate was better than chance. We conclude that estimating EEG-based
      functional connectivity provides a useful tool for studying the relationship
      between brain activity and emotional states. 

PMID- 24743697
TI  - The gammaH2AX assay for genotoxic and nongenotoxic agents: comparison of H2AX
      phosphorylation with cell death response.
AB  - DNA double-strand breaks (DSBs) and blocked replication forks resulting from
      bulky adducts and inhibitors of replication activate the DNA damage response
      (DDR), a signaling pathway marked by phosphorylation of histone 2AX (H2AX). The
      phosphorylated form, gammaH2AX, accumulates at the site of the damage and can be
      visualized as foci by immunocytochemistry. The objective of this study was to
      assess if gammaH2AX is a reliable biomarker for genotoxic exposures. To this end,
      we selected 14 well-known genotoxic compounds and compared them with 10
      nongenotoxic chemicals, using CHO-9 cells because they are well characterized as
      to DNA repair and DDR. We quantified gammaH2AX foci manually and automatically.
      In addition, total gammaH2AX activation was determined by flow cytometry. For all
      chemicals the cytotoxic dose response was assayed by a metabolic cytotoxicity
      assay. We show that (1) all genotoxic agents induced gammaH2AX dose-dependently
      whereas nongenotoxic agents do not; (2) gammaH2AX was observed for genotoxicants
      in the cytotoxic dose range, revealing a correlation between cytotoxicity and
      gammaH2AX for genotoxic agents; for nongenotoxic agents cytotoxicity was not
      related to gammaH2AX; (3) manual scoring of gammaH2AX and automated scoring
      provided comparable results, the automated scoring was faster and investigator
      independent; (4) data obtained by foci counting and flow cytometry showed a high
      correlation, suggesting that gammaH2AX scoring by flow cytometry has the
      potential for high-throughput analysis. However, the microscopic evaluation can
      provide additional information as to foci size, distribution, colocalization and
      background staining; (5) gammaH2AX foci were colocalized with 53BP1 and Rad51,
      supporting the notion that they represent true DSBs. Collectively, the automated
      analysis of gammaH2AX foci allows for rapid determination of genetic damage in
      mammalian cells. The data revealed that the induction of gammaH2AX by
      genotoxicants is related to loss of viability and support gammaH2AX as a reliable
      bio-indicator for pretoxic DNA damage. 

PMID- 24743696
TI  - Potent dengue virus neutralization by a therapeutic antibody with low monovalent
      affinity requires bivalent engagement.
AB  - We recently described our most potently neutralizing monoclonal antibody, E106,
      which protected against lethal Dengue virus type 1 (DENV-1) infection in mice. To
      further understand its functional properties, we determined the crystal structure
      of E106 Fab in complex with domain III (DIII) of DENV-1 envelope (E) protein to
      2.45 A resolution. Analysis of the complex revealed a small antibody-antigen
      interface with the epitope on DIII composed of nine residues along the lateral
      ridge and A-strand regions. Despite strong virus neutralizing activity of E106
      IgG at picomolar concentrations, E106 Fab exhibited a ~20,000-fold decrease in
      virus neutralization and bound isolated DIII, E, or viral particles with only a
      micromolar monovalent affinity. In comparison, E106 IgG bound DENV-1 virions with
      nanomolar avidity. The E106 epitope appears readily accessible on virions, as
      neutralization was largely temperature-independent. Collectively, our data
      suggest that E106 neutralizes DENV-1 infection through bivalent engagement of
      adjacent DIII subunits on a single virion. The isolation of anti-flavivirus
      antibodies that require bivalent binding to inhibit infection efficiently may be
      a rare event due to the unique icosahedral arrangement of envelope proteins on
      the virion surface. 

PMID- 24743698
TI  - Endogenous dopamine is involved in the herbicide paraquat-induced dopaminergic
      cell death.
AB  - The herbicide paraquat is an environmental factor that may be involved in the
      etiology of Parkinson's disease (PD). Systemic exposure of mice to paraquat
      causes a selective loss of dopaminergic neurons in the substantia nigra pars
      compacta, although paraquat is not selectively incorporated in dopaminergic
      neurons. Here, we report a contribution of endogenous dopamine to paraquat
      induced dopaminergic cell death. Exposure of PC12 cells to paraquat (50MUM)
      caused delayed toxicity from 36 h onward. A decline in intracellular dopamine
      content achieved by inhibiting tyrosine hydroxylase (TH), an enzyme for dopamine
      synthesis, conferred resistance to paraquat toxicity on dopaminergic cells.
      Paraquat increased the levels of cytosolic and vesicular dopamine, accompanied by
      transiently increased TH activity. Quinone derived from cytosolic dopamine
      conjugates with cysteine residues in functional proteins to form quinoproteins.
      Formation of quinoprotein was transiently increased early during exposure to
      paraquat. Furthermore, pretreatment with ascorbic acid, which suppressed the
      elevations of intracellular dopamine and quinoprotein, almost completely
      prevented paraquat toxicity. These results suggest that the elevation of
      cytosolic dopamine induced by paraquat participates in the vulnerability of
      dopaminergic cells to delayed toxicity through the formation of quinoproteins. 

PMID- 24743699
TI  - Cross-linking of beta-lactoglobulin enhances allergic sensitization through
      changes in cellular uptake and processing.
AB  - Cross-linking of proteins has been exploited by the food industry to change food
      texture and functionality but the effects of these manipulations on food
      allergenicity still remain unclear. To model the safety assessment of these food
      biopolymers, we created cross-linked bovine beta-lactoglobulin (CL-BLG) by
      laccase treatment. The purpose of the present study was to compare the
      immunogenicity and allergenicity of CL-BLG with native BLG in a mouse model of
      food allergy. First, BALB/c mice were intragastrically sensitized and orally
      challenged with BLG or CL-BLG and BLG-specific serum antibodies and splenic
      leukocyte cytokine production and cell proliferation were measured. Hereafter,
      epithelial protein uptake was monitored in vitro and in vivo and the effects of
      BLG cross-linking on interactions with dendritic cells were analyzed in vitro.
      Sensitization of mice with CL-BLG resulted in higher levels of IgE, IgG1, and
      IgG2a. In contrast, a subsequent oral challenge with CL-BLG resulted in lower
      mast cell degranulation. Cross-linking of BLG reduced its epithelial uptake but
      promoted sampling through Peyer's patches. Differences in endocytosis by
      dendritic cells (DCs) and in vitro endolysosomal processing were observed between
      BLG and CL-BLG. CL-BLG primed DCs induced higher Th2 response in vitro. Cross
      linking of BLG increased its sensitizing capacity, implying that the assessment
      of highly polymerized food proteins is of clinical importance in food allergy.
      Moreover, manufacturers of foods or therapeutic proteins should pay considerate
      attention to the health risk of protein aggregation. 

PMID- 24743700
TI  - Toxicity studies of WY-14,643 (CAS No. 50892-23-4) administered in feed to male
      Sprague-Dawley rats, B6C3F1 mice, and Syrian hamsters.
AB  - Wy-14,643 was selected for inclusion in a series of studies on peroxisome
      proliferators because it is known to produce considerable peroxisome
      proliferation and hepatocarcinogenicity in rats. Male Sprague-Dawley rats were
      exposed to Wy-14,643 (greater than 98% pure) in feed for up to 3 months; male
      B6C3F1 mice and male Syrian hamsters were exposed to Wy-14,643 in feed for 2
      weeks or up to 3 months. Animals were evaluated for clinical pathology, plasma
      concentrations of Wy-14,643, reproductive system effects, cell proliferation and
      peroxisomal enzyme analyses, and histopathology. Single and multiple-dose
      toxicokinetic studies of Wy-14,643 were conducted in additional groups of male
      Sprague-Dawley and Wistar Furth rats, B6C3F1 mice, and Syrian hamsters. Genetic
      toxicology studies were conducted in vivo in Tg.AC mouse peripheral blood
      erythrocytes. In the 2-week studies, groups of five mice were fed diets
      containing 0, 10, 50, 100, 500, or 1,000 ppm Wy-14,643 (equivalent to average
      daily doses of approximately 2 to 184 mg Wy-14,643/kg body weight). Groups of
      five hamsters were fed diets containing 0, 10, 100, 500, 1,000, or 5,000 ppm Wy
      14,643 (equivalent to average daily doses of approximately 1 to 550 mg/kg). All
      animals survived to the end of the studies. The mean body weight gain of 500 ppm
      mice was significantly less than that of the controls; hamsters exposed to 100
      ppm or greater lost weight during the study. Feed consumption by 500 ppm mice was
      greater than that by the controls. Liver weights of all exposed groups of mice
      and hamsters were generally significantly increased. In the 2-week studies, an
      increase in peroxisomal enzyme activity occurred in 10 ppm mice; increases in
      peroxisomal $-oxidation, carnitine acetyltransferase, catalase, and acyl CoA
      oxidase occurred in all exposed mice compared to controls. Significantly
      increased BrdU-labeled hepatocyte percentages occurred in 100 and 1,000 ppm mice
      and 500 and 5,000 ppm hamsters; peroxisomal $-oxidation of lipids was increased
      in all exposed groups of mice and hamsters. Gross lesions in the 2-week studies
      included liver foci in one 500 ppm mouse and one 1,000 ppm hamster and enlarged
      livers in one hamster in each of the 100 and 500 ppm groups and two 5,000 ppm
      hamsters. All 500 and 1,000 ppm mice had hepatocyte hypertrophy of the liver, and
      1,000 ppm mice also had widespread individual cell necrosis. Minimal to mild
      multifocal vacuolation of the liver occurred in hamsters exposed to 500 ppm or
      greater. In the 3-month core studies, groups of 10 male rats, mice, or hamsters
      were fed diets containing 0, 5, 10, 50, 100, or 500 ppm Wy-14,643 (equivalent to
      average daily doses of approximately 0.3 to 34 mg/kg for rats, 0.9 to 135 mg/kg
      for mice, and 0.4 to 42 mg/kg for hamsters). Groups of 15 male rats, mice, or
      hamsters designated for special studies received the same concentrations of Wy
      14,643 for up to 13 weeks. Groups of six male rats, 36 male mice, or 12 male
      hamsters designated for plasma concentration studies were fed diets containing
      50, 100, or 500 ppm Wy-14,643 for up to 9 weeks. All core study animals survived
      to the end of the studies. Mean body weights were significantly decreased in all
      exposed groups except the 5 ppm groups and 10 ppm mice; hamsters in the 100 and
      500 ppm groups lost weight during the study. Feed consumption by exposed rats and
      mice was generally similar to that by the controls; during week 14, hamsters
      exposed to 50 ppm or greater consumed slightly less feed than did the controls.
      The only clinical finding of toxicity was thinness of two 50 ppm and five 500 ppm
      hamsters. At all time points, the liver weights of exposed groups of core and
      special study rats, mice, and hamsters were generally significantly greater than
      those of the controls. Testis weights were significantly decreased in 500 ppm
      hamsters on day 34, in hamsters exposed to 5 ppm or greater at week 13 (special
      study), and in 100 and 500 ppm core study hamsters at the end of the study. In
      the sperm motility evaluation, the cauda epididymis weight of 500 ppm rats,
      epididymis weights of 100 and 500 ppm rats and mice, and the testis weight of 500
      ppm mice were significantly less than those of the controls. For hamsters, cauda
      epididymis, epididymis, and testis weights; spermatid heads per testis; and
      spermatid counts were significantly decreased in all exposed groups evaluated for
      sperm motility. Epididymal spermatozoal motility and concentration in the 100 and
      500 ppm groups and spermatid heads per gram testis in the 500 ppm group were also
      significantly decreased. Serum concentrations of estradiol were significantly
      decreased in all exposed groups of hamsters, and concentrations of testosterone
      and luteinizing hormone were decreased in groups exposed to 50 ppm or greater. At
      necropsy in the 3-month studies, liver foci were observed in three special study
      mice, including one 100 ppm mouse and one 500 ppm mouse on day 34 and one 100 ppm
      mouse at week 13. Liver discoloration and small testes were noted in 500 ppm
      hamsters on day 34, and hamsters exposed to 50 ppm or greater had enlarged livers
      and/or small testes at week 13 (special study) and at 3 months (core study). The
      incidences of cytoplasmic alteration in the liver were significantly increased in
      all exposed core groups of rats, mice, and hamsters; the severity of this lesion
      increased with increasing exposure concentration. The incidences of mitotic
      alteration of the liver in mice exposed to 50 ppm or greater and of liver
      pigmentation and oval cell hyperplasia in 500 ppm mice were significantly
      increased. Minimal regeneration of the corticomedullary junction of the renal
      tubule occurred in all exposed groups of rats. Significantly increased incidences
      of atrophy of the prostate gland, seminal vesicle, and testis occurred in 100 and
      500 ppm hamsters. Degenerative myopathy of skeletal muscle was observed in the
      lumbar area and thigh of rats, mice, and hamsters and the lower leg of mice,
      primarily at 500 ppm. Following single-dose gavage exposure to Wy-14,643, plasma
      concentrations were generally higher in mice than in rats, which in turn were
      higher than those in hamsters. This pattern of plasma concentrations was usually
      attributed to high bioavailability in mice, medium bioavailability in rats, and
      low bioavailabilty in hamsters following an oral exposure to Wy-14,643. No
      increase in the frequency of micronucleated normochromatic erythrocytes was
      observed in the peripheral blood of male or female Tg.AC mice exposed to Wy
      14,643 in feed or via dermal application for 6 months. Synonyms: [4-Chloro-6-(2,3
      xylidino)-2-pyrimidinylthio]acetic acid.

PMID- 24743702
TI  - Genome-wide analysis of copy number variation identifies candidate gene loci
      associated with the progression of non-alcoholic fatty liver disease.
AB  - Between 10 and 25% of individuals with non-alcoholic fatty liver disease (NAFLD)
      develop hepatic fibrosis leading to cirrhosis and hepatocellular carcinoma (HCC).
      To investigate the molecular basis of disease progression, we performed a genome
      wide analysis of copy number variation (CNV) in a total of 49 patients with NAFLD
      [10 simple steatosis and 39 non-alcoholic steatohepatitis (NASH)] and 49 matched
      controls using high-density comparative genomic hybridization (CGH) microarrays.
      A total of 11 CNVs were found to be unique to individuals with simple steatosis,
      whilst 22 were common between simple steatosis and NASH, and 224 were unique to
      NASH. We postulated that these CNVs could be involved in the pathogenesis of
      NAFLD progression. After stringent filtering, we identified four rare and/or
      novel CNVs that may influence the pathogenesis of NASH. Two of these CNVs,
      located at 13q12.11 and 12q13.2 respectively, harbour the exportin 4 (XPO4) and
      phosphodiesterase 1B (PDE1B) genes which are already known to be involved in the
      etiology of liver cirrhosis and HCC. Cross-comparison of the genes located at
      these four CNV loci with genes already known to be associated with NAFLD yielded
      a set of genes associated with shared biological processes including cell death,
      the key process involved in 'second hit' hepatic injury. To our knowledge, this
      pilot study is the first to provide CNV information of potential relevance to the
      NAFLD spectrum. These data could prove invaluable in predicting patients at risk
      of developing NAFLD and more importantly, those who will subsequently progress to
      NASH.

PMID- 24743703
TI  - Moguntinones--new selective inhibitors for the treatment of human colorectal
      cancer.
AB  - 3-Indolyl and 3-azaindolyl-4-aryl maleimide derivatives, called moguntinones
      (MOG), have been selected for their ability to inhibit protein kinases associated
      with angiogenesis and induce apoptosis. Here, we characterize their mode of
      action and their potential clinical value in human colorectal cancer in vitro and
      in vivo. MOG-19 and MOG-13 were characterized in vitro using kinase, viability,
      and apoptosis assays in different human colon cancer (HT-29, HCT-116, Caco-2, and
      SW480) and normal colon cell lines (CCD-18Co, FHC, and HCoEpiC) alone or in
      combination with topoisomerase I inhibitors. Intracellular signaling pathways
      were analyzed by Western blotting. To determine their potential to inhibit tumor
      growth in vivo, the human HT-29 tumor xenograft model was used. Moguntinones
      prominently inhibit several protein kinases associated with tumor growth and
      metastasis. Specific signaling pathways such as GSK3beta and mTOR downstream
      targets were inhibited with IC(50) values in the nanomolar range. GSK3beta
      signaling inhibition was independent of KRAS, BRAF, and PI3KCA mutation status.
      While moguntinones alone induced apoptosis only in concentrations >10 MUmol/L,
      MOG-19 in combination with topoisomerase I inhibitors induced apoptosis
      synergistically at lower concentrations. Consistent with in vitro data, MOG-19
      significantly reduced tumor volume and weight in combination with a topoisomerase
      I inhibitor in vivo. Our in vitro and in vivo data present significant
      proapoptotic, antiangiogenic, and antiproliferative effects of MOG-19 in
      different human colon cancer cells. Combination with clinically relevant
      topoisomerase I inhibitors in vitro and xenograft mouse model demonstrate a high
      potency of moguntinones to complement and improve standard chemotherapy options
      in human colorectal cancer.

PMID- 24743704
TI  - Coexistence of EGFR with KRAS, or BRAF, or PIK3CA somatic mutations in lung
      cancer: a comprehensive mutation profiling from 5125 Chinese cohorts.
AB  - BACKGROUND: Determining the somatic mutations of epidermal growth factor receptor
      (EGFR)-pathway networks is the key to effective treatment for non-small cell lung
      cancer (NSCLC) with tyrosine kinase inhibitors (TKIs).The somatic mutation
      frequencies and their association with gender, smoking history and histology was
      analysed and reported in this study. METHODS: Five thousand one hundred and
      twenty-five NSCLC patients' pathology samples were collected, and EGFR, KRAS,
      BRAF and PIK3CA mutations were detected by multiplex testing. The mutation status
      of EGFR, KRAS, BRAF and PIK3CA and their association with gender, age, smoking
      history and histological type were evaluated by appropriate statistical analysis.
      RESULTS: EGFR, KRAS, BRAF and PIK3CA mutation rates revealed 36.2%, 8.4%, 0.5%
      and 3.3%, respectively, across the 5125 pathology samples. For the first time,
      evidence of KRAS mutations were detected in two female, non-smoking patients, age
      5 and 14, with NSCLC. Furthermore, we identified 153 double and coexisting
      mutations and 7 triple mutations. Interestingly, the second drug-resistant
      mutations, T790M or E545K, were found in 44 samples from patients who had never
      received TKI treatments. CONCLUSIONS: EGFR exons 19, 20 and 21, and BRAF
      mutations tend to happen in females and non-smokers, whereas KRAS mutations were
      more inclined to males and smokers. Activating and resistant mutations to EGFR
      TKI drugs can coexist and 'second drug-resistant mutations', T790M or E545K, may
      be primary mutations in some patients. These results will help oncologists to
      decide candidates for mutation testing and EGFR-TKI treatment.

PMID- 24743705
TI  - Effects of erythropoiesis-stimulating agents on fatigue- and anaemia-related
      symptoms in cancer patients: systematic review and meta-analyses of published and
      unpublished data.
AB  - BACKGROUND: Erythropoiesis-stimulating agents (ESAs) reduce the need for red
      blood cell transfusions; however, they increase the risk of thromboembolic events
      and mortality. The impact of ESAs on quality of life (QoL) is controversial and
      led to different recommendations of medical societies and authorities in the USA
      and Europe. We aimed to critically evaluate and quantify the effects of ESAs on
      QoL in cancer patients. METHODS: We included data from randomised controlled
      trials (RCTs) on the effects of ESAs on QoL in cancer patients. Randomised
      controlled trials were identified by searching electronic data bases and other
      sources up to January 2011. To reduce publication and outcome reporting biases,
      we included unreported results from clinical study reports. We conducted meta
      analyses on fatigue- and anaemia-related symptoms measured with the Functional
      Assessment of Cancer Therapy-Fatigue (FACT-F) and FACT-Anaemia (FACT-An)
      subscales (primary outcomes) or other validated instruments. RESULTS: We
      identified 58 eligible RCTs. Clinical study reports were available for 27% (4 out
      of 15) of the investigator-initiated trials and 95% (41 out of 43) of the
      industry-initiated trials. We excluded 21 RTCs as we could not use their QoL data
      for meta-analyses, either because of incomplete reporting (17 RCTs) or because of
      premature closure of the trial (4 RCTs). We included 37 RCTs with 10581 patients;
      21 RCTs were placebo controlled. Chemotherapy was given in 27 of the 37 RCTs. The
      median baseline haemoglobin (Hb) level was 10.1 g dl(-1); in 8 studies ESAs were
      stopped at Hb levels below 13 g dl(-1) and in 27 above 13 g dl(-1). For FACT-F,
      the mean difference (MD) was 2.41 (95% confidence interval (95% CI) 1.39-3.43;
      P<0.0001; 23 studies, n=6108) in all cancer patients and 2.81 (95% CI 1.73-3.90;
      P<0.0001; 19 RCTs, n=4697) in patients receiving chemotherapy, which was below
      the threshold (>= 3) for a clinically important difference (CID). Erythropoiesis
      stimulating agents had a positive effect on anaemia-related symptoms (MD 4.09;
      95% CI 2.37-5.80; P=0.001; 14 studies, n=2765) in all cancer patients and 4.50
      (95% CI 2.55-6.45; P<0.0001; 11 RCTs, n=2436) in patients receiving chemotherapy,
      which was above the threshold (>= 4) for a CID. Of note, this effect persisted
      when we restricted the analysis to placebo-controlled RCTs in patients receiving
      chemotherapy. There was some evidence that the MDs for FACT-F were above the
      threshold for a CID in RCTs including cancer patients receiving chemotherapy with
      Hb levels below 12 g dl(-1) at baseline and in RCTs stopping ESAs at Hb levels
      above 13 g dl(-1). However, these findings for FACT-F were not confirmed when we
      restricted the analysis to placebo-controlled RCTs in patients receiving
      chemotherapy. CONCLUSIONS: In cancer patients, particularly those receiving
      chemotherapy, we found that ESAs provide a small but clinically important
      improvement in anaemia-related symptoms (FACT-An). For fatigue-related symptoms
      (FACT-F), the overall effect did not reach the threshold for a CID.

PMID- 24743706
TI  - A feasibility study testing four hypotheses with phase II outcomes in advanced
      colorectal cancer (MRC FOCUS3): a model for randomised controlled trials in the
      era of personalised medicine?
AB  - BACKGROUND: Molecular characteristics of cancer vary between individuals. In
      future, most trials will require assessment of biomarkers to allocate patients
      into enriched populations in which targeted therapies are more likely to be
      effective. The MRC FOCUS3 trial is a feasibility study to assess key elements in
      the planning of such studies. PATIENTS AND METHODS: Patients with advanced
      colorectal cancer were registered from 24 centres between February 2010 and April
      2011. With their consent, patients' tumour samples were analysed for KRAS/BRAF
      oncogene mutation status and topoisomerase 1 (topo-1) immunohistochemistry.
      Patients were then classified into one of four molecular strata; within each
      strata patients were randomised to one of two hypothesis-driven experimental
      therapies or a common control arm (FOLFIRI chemotherapy). A 4-stage suite of
      patient information sheets (PISs) was developed to avoid patient overload.
      RESULTS: A total of 332 patients were registered, 244 randomised. Among
      randomised patients, biomarker results were provided within 10 working days
      (w.d.) in 71%, 15 w.d. in 91% and 20 w.d. in 99%. DNA mutation analysis was 100%
      concordant between two laboratories. Over 90% of participants reported excellent
      understanding of all aspects of the trial. In this randomised phase II setting,
      omission of irinotecan in the low topo-1 group was associated with increased
      response rate and addition of cetuximab in the KRAS, BRAF wild-type cohort was
      associated with longer progression-free survival. CONCLUSIONS: Patient samples
      can be collected and analysed within workable time frames and with reproducible
      mutation results. Complex multi-arm designs are acceptable to patients with good
      PIS. Randomisation within each cohort provides outcome data that can inform
      clinical practice.

PMID- 24743707
TI  - Regulation of somatostatin receptor 4-mediated cytostatic effects by CD26 in
      malignant pleural mesothelioma.
AB  - BACKGROUND: Malignant pleural mesothelioma (MPM) is an aggressive neoplasm
      arising from mesothelial lining of pleura. CD26 molecules preferentially
      expressed on epithelioid type of MPM. This study investigates the molecular
      mechanisms of CD26 regulating MPM cells in vitro and in vivo. METHODS:
      Biochemical and cell biological approaches were used for identifying a novel
      molecular target of MPM. Its contribution to tumour expansion has been also
      assessed using animal models. The clinical samples of MPM were also assessed for
      its expression. RESULTS: We identify that cytostatic effects in MPM are mediated
      by somatostatin (SST) receptor 4 (SSTR4), being inhibited by the interaction of
      CD26 molecules. We also indicates that SSTR4-mediated cytostatic effects are
      regulated by SHP-2 PTP, and that this inhibitory effect by SST agonist is
      enhanced via lipid raft clustering of associated molecules following crosslinking
      of anti-CD26 antibody. Finally, using an in vivo xenograft model, we demonstrate
      that the anti-tumour effect of anti-CD26 mAb is enhanced when combined with SSTR4
      agonist treatment, and that SSTR4 is highly coexpressed with CD26 on epithelioid
      or biphasic types of MPM tissues obtained from patients' surgical specimens.
      CONCLUSIONS: Combination therapy with humanised anti-CD26 mAb and SSTR4 agonist
      may therefore potentiate anti-tumour effect on MPM.

PMID- 24743708
TI  - Long-term survivor characteristics in HER2-positive metastatic breast cancer from
      registHER.
AB  - BACKGROUND: Data characterising long-term survivors (LTS) with human epidermal
      growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC) are
      limited. This analysis describes LTS using registHER observational study data.
      METHODS: A latent class modelling (LCM) approach was used to identify distinct
      homogenous patient groups (or classes) based on progression-free survival (PFS),
      overall survival, and complete response. Demographics, clinicopathologic factors,
      first-line treatment patterns, and clinical outcomes were described for each
      class. Class-associated factors were evaluated using logistic regression
      analysis. RESULTS: LCM identified two survivor groups labelled as LTS (n=244) and
      short-term survivors (STS; n=757). Baseline characteristics were similar between
      groups, although LTS were more likely to be white (83.6% vs 77.8%) with oestrogen
      receptor-positive (ER+) or progesterone receptor-positive (PgR+) disease (59.4%
      vs 50.9%). Median PFS in LTS was 37.2 (95% confidence interval (CI): 32.9-40.5)
      vs 7.3 months (95% CI: 6.8-8.0) in STS. Factors associated with long-term
      survival included ER+ or PgR+ disease, metastasis to node/local sites, first-line
      trastuzumab use, and first-line taxane use. CONCLUSIONS: Prognostic variables
      identified by LCM define a HER2-positive MBC patient profile and therapies that
      may be associated with more favourable long-term outcomes, enabling treatment
      selection appropriate to the patient's disease characteristics.

PMID- 24743709
TI  - Does change in health-related quality of life score predict survival? Analysis of
      EORTC 08975 lung cancer trial.
AB  - BACKGROUND: Little is known about whether changes in health-related quality of
      life (HRQoL) scores from baseline during treatment also predict survival, which
      we aim to investigate in this study. METHODS: We analysed data from 391 advanced
      non-small-cell lung cancer (NSCLC) patients enrolled in the EORTC 08975 study,
      which compared palliative chemotherapy regimens. HRQoL was assessed at baseline
      and after each chemotherapy cycle using the EORTC QLQ-C30 and QLQ-LC13. The
      prognostic significance of HRQoL scores at baseline and their changes over time
      was assessed with Cox regression, after adjusting for clinical and socio
      demographic variables. RESULTS: After controlling for covariates, every 10-point
      increase in baseline pain and dysphagia was associated with 11% and 12% increased
      risk of death with hazard ratios (HRs) of 1.11 and 1.12, respectively. Every 10
      point improvement of physical function at baseline (HR=0.93) was associated with
      7% lower risk of death. Every 10-point increase in pain (HR=1.08) was associated
      with 8% increased risk of death at cycle 1. Every 10-point increase in social
      function (HR=0.91) at cycle 2 was associated with 9% lower risk of death.
      CONCLUSIONS: Our findings suggest that changes in HRQoL scores from baseline
      during treatment, as measured on subscales of the EORTC QLQ-C30 and QLQ-LC13, are
      significant prognostic factors for survival.

PMID- 24743710
TI  - Hypoxia enhances the antiglioma cytotoxicity of B10, a glycosylated derivative of
      betulinic acid.
AB  - B10 is a glycosylated derivative of betulinic acid with promising activity
      against glioma cells. Lysosomal cell death pathways appear to be essential for
      its cytotoxicity. We investigated the influence of hypoxia, nutrient deprivation
      and current standard therapies on B10 cytotoxicity. The human glioma cell lines
      LN-308 and LNT-229 were exposed to B10 alone or together with irradiation,
      temozolomide, nutrient deprivation or hypoxia. Cell growth and viability were
      evaluated by crystal violet staining, clonogenicity assays, propidium iodide
      uptake and LDH release assays. Cell death was examined using an inhibitor of
      lysosomal acidification (bafilomycin A1), a cathepsin inhibitor (CA074-Me) and a
      short-hairpin RNA targeting cathepsin B. Hypoxia substantially enhanced B10
      induced cell death. This effect was sensitive to bafilomycin A1 and thus
      dependent on hypoxia-induced lysosomal acidification. Cathepsin B appeared to
      mediate cell death because either the inhibitor CA074-Me or cathepsin B gene
      silencing rescued glioma cells from B10 toxicity under hypoxia. B10 is a novel
      antitumor agent with substantially enhanced cytotoxicity under hypoxia conferred
      by increased lysosomal cell death pathway activation. Given the importance of
      hypoxia for therapy resistance, malignant progression, and as a result of
      antiangiogenic therapies, B10 might be a promising strategy for hypoxic tumors
      like malignant glioma. 

PMID- 24743711
TI  - How the brain decides when to work and when to rest: dissociation of implicit
      reactive from explicit-predictive computational processes.
AB  - A pervasive case of cost-benefit problem is how to allocate effort over time,
      i.e. deciding when to work and when to rest. An economic decision perspective
      would suggest that duration of effort is determined beforehand, depending on
      expected costs and benefits. However, the literature on exercise performance
      emphasizes that decisions are made on the fly, depending on physiological
      variables. Here, we propose and validate a general model of effort allocation
      that integrates these two views. In this model, a single variable, termed cost
      evidence, accumulates during effort and dissipates during rest, triggering effort
      cessation and resumption when reaching bounds. We assumed that such a basic
      mechanism could explain implicit adaptation, whereas the latent parameters
      (slopes and bounds) could be amenable to explicit anticipation. A series of
      behavioral experiments manipulating effort duration and difficulty was conducted
      in a total of 121 healthy humans to dissociate implicit-reactive from explicit
      predictive computations. Results show 1) that effort and rest durations are
      adapted on the fly to variations in cost-evidence level, 2) that the cost
      evidence fluctuations driving the behavior do not match explicit ratings of
      exhaustion, and 3) that actual difficulty impacts effort duration whereas
      expected difficulty impacts rest duration. Taken together, our findings suggest
      that cost evidence is implicitly monitored online, with an accumulation rate
      proportional to actual task difficulty. In contrast, cost-evidence bounds and
      dissipation rate might be adjusted in anticipation, depending on explicit task
      difficulty. 

PMID- 24743712
TI  - Quetiapine extended release: preliminary evidence of a rapid onset of the
      antidepressant effect in bipolar depression.
AB  - BACKGROUND AND AIMS: Quetiapine (QTP) has been shown to be effective as an acute
      treatment in patients with bipolar depression. Nonetheless, the time at onset of
      QTP antidepressant action has not been clarified. We aimed to evaluate the onset
      of the antidepressant effect of QTP extended release (XR) in bipolar depression.
      We also compared the different efficacy and adverse effect profile of 300- and
      600-mg/d dosages. METHODS: Twenty-one acutely bipolar depressed patients were
      recruited; 13 were treated with QTP XR 300 and 8 with 600 mg/d. Assessment was
      performed with Hamilton Depression Rating Scale (also considering clusters
      "core," "somatic anxiety," "psychic anxiety," "activity," and "delusion"),
      Hamilton Anxiety Rating Scale, Dosage Record and Treatment Emergent Symptom
      Scale. RESULTS: Quetiapine XR was effective since the first 3 days of treatment
      in reducing all the efficacy measures except for somatic anxiety. The comparison
      of 300- and 600-mg dosages was limited by the small sample size. However, the
      analysis did not show any significant difference in terms of efficacy, although
      with a trend in favor of 600 mg. The incidence of hypotension was significantly
      higher in patients taking QTP 600 mg (P = 0.004). DISCUSSION AND CONCLUSION:
      Quetiapine seems to be effective in bipolar depression within the first days of
      treatment. There may be not a significant advantage for the 600-mg dose in
      comparison with the 300-mg one. The clinical effect seems to be not associated
      with sedation, suggesting that it may be due to the molecular drug effect.
      Further studies focusing on the first days of treatment are needed to confirm our
      findings.

PMID- 24743713
TI  - Treatment outcomes of depression: the pharmacogenomic research network
      antidepressant medication pharmacogenomic study.
AB  - BACKGROUND: The effectiveness of selective serotonin reuptake inhibitors (SSRIs)
      in patients with major depressive disorder (MDD) is controversial. AIMS: The
      clinical outcomes of subjects with nonpsychotic MDD were reported and compared
      with the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study
      outcomes to provide guidance on the effectiveness of SSRIs. METHODS: Subjects
      were treated with citalopram/escitalopram for up to 8 weeks. Depression was
      measured using the Quick Inventory of Depressive Symptomatology-Clinician Rated
      (QIDS-C16) and the 17-item Hamilton Depression Rating Scale. RESULTS: The group
      of subjects with at least 1 follow-up visit had a remission (QIDS-C16 <= 5) rate
      of 45.8% as well as a response (50% reduction in QIDS-C16) rate of 64.8%, and
      79.9% achieved an improvement of 5 points or higher in QIDS-C16 score. The
      Pharmacogenomic Research Network Antidepressant Medication Pharmacogenomic Study
      subjects were more likely to achieve a response than STAR*D study subjects. After
      adjustment for demographic factors, the response rates were not significantly
      different. When reporting the adverse effect burden, 60.5% of the subjects
      reported no impairment, 31.7% reported a minimal-to-mild impairment, and 7.8%
      reported a moderate-to-severe burden at the 4-week visit. CONCLUSIONS: Patients
      contemplating initiating an SSRI to treat their MDD can anticipate a high
      probability of symptom improvement (79.9%) with a low probability that their
      symptoms will become worse. Patients with lower baseline severity have a higher
      probability of achieving remission. The Pharmacogenomic Research Network
      Antidepressant Medication Pharmacogenomic Study replicates many findings of the
      first phase of the STAR*D study after controlling for the differences between the
      studies.

PMID- 24743714
TI  - SLC17A7 gene may be the indicator of selective serotonin reuptake inhibitor
      treatment response in the Chinese Han population.
AB  - Selective serotonin reuptake inhibitors (SSRIs) are widely used drugs for major
      depressive disorder (MDD), although the treatment outcomes vary in different
      people. The vesicular glutamate transporter 1 coded by SLC17A7 gene has been
      reported associated with MDD. According to its role in glutamate transmission, it
      is reasonable to consider it as a potential pharmacogenetic candidate in SSRI
      treatment. A total of 290 MDD patients who had been taking SSRIs for 6 weeks were
      recruited. Their genotypes were assessed for the presence of 4 single-nucleotide
      polymorphisms, which were selected from either the HapMap Chinese ethnic group or
      the literature report. Treatment effects were evaluated by the change rate of
      Hamilton Rating Scale for Depression. After the adjustment for the false
      discovery rate, 1 single-nucleotide polymorphism (rs74174284, false discovery
      rate; P = 0.032) demonstrated significant association with SSRI treatment
      response at week 6. Our results suggest that genetic variants in the SLC17A7 gene
      may be indicators of treatment response in MDD patients treated by SSRIs. 

PMID- 24743715
TI  - Intrathecal baclofen improves psychiatric symptoms in spasticity patients.
AB  - Symptoms of psychological distress are relatively common in spasticity patients
      as a result either of the primary central nervous system insult or as a reaction
      to the ensuing impairment. Intrathecal baclofen (ITB) is an established treatment
      for the spasticity with an unknown effect on the psychiatric symptoms. In this
      study, we evaluate the role of ITB in the amelioration of psychological distress
      symptoms in 15 patients who were not mentally disabled or psychotic. The patients
      were assessed with the Symptom Check List 90-Revised before and a mean of 12
      months after ITB treatment. A significant improvement was noted at the subscales
      of positive symptoms total and anxiety. The anxiety subscale improvement was
      correlated with the ITB dose, but not with the reduction in the spasticity. An
      interesting trend was also noted in the subscales of general severity index,
      depression, and obsession-compulsion. The results show an additional beneficial
      effect of ITB and highlight the need of further clarification of the causative
      mechanism. 

PMID- 24743716
TI  - Plasma levels and cerebrospinal fluid penetration of venlafaxine in a patient
      with a nonfatal overdose during a suicide attempt.

PMID- 24743717
TI  - A double-blind, randomized comparison study of efficacy and safety of
      intramuscular olanzapine and intramuscular haloperidol in patients with
      schizophrenia and acute agitated behavior.
AB  - Studies of intramuscular (IM) olanzapine in Asian and Taiwanese populations are
      limited. This study examined the efficacy and safety of IM olanzapine in
      Taiwanese patients with schizophrenia and acute agitated behavior.This was a
      multicenter, double-blind, randomized, parallel study comparing the efficacy and
      safety of 10 mg/d IM olanzapine (n = 25) against 7.5 mg/d haloperidol (n = 24).
      The primary objective was to assess the change of agitation from baseline to 2
      hours after the first IM injection on the Positive and Negative Symptom Scale
      Excited Component Scale.The changes of Positive and Negative Symptom Scale
      Excited Component Scale score from baseline to 2 hours after the first IM
      injection did not show statistically significant difference between study groups
      (olanzapine -9.0 +/- 5.7, haloperidol -7.9 +/- 4.0, P = 0.254). Both groups
      reported insomnia as the most common treatment-emergent adverse event, and no
      serious adverse event was reported.Intramuscular olanzapine and IM haloperidol
      are similarly effective antipsychotic agents in treating agitated symptoms in
      Taiwanese patients with schizophrenia. Both IM olanzapine and IM haloperidol were
      proven to be safe and well tolerated, which also provided alternative options in
      the treatment of patients with schizophrenia with agitation. 

PMID- 24743718
TI  - Plasma fluoxetine concentrations and clinical improvement in an adolescent sample
      diagnosed with major depressive disorder, obsessive-compulsive disorder, or
      generalized anxiety disorder.
AB  - Fluoxetine (FLX) has been one of the most widely studied selective serotonin
      reuptake inhibitors in adolescents. Despite its efficacy, however, 30% to 40% of
      patients do not respond to treatment. AIMS: The aim of this study was to evaluate
      whether clinical improvement or adverse events are related to the corrected dose
      of FLX at 8 and 12 weeks after starting treatment in a sample of adolescents
      diagnosed with major depressive disorder, obsessive-compulsive disorder, or
      generalized anxiety disorder. METHODS: Seventy-four subjects aged between 10 and
      17 years participated in the study. Clinical improvement was measured with the
      Clinical Global Impression-Improvement Scale, whereas the UKU (Udvalg for Klinske
      Undersogelser) scale was administered to assess adverse effects of treatment.
      RESULTS: Fluoxetine per kilograms of body weight was related to serum
      concentration of FLX, NORFLX (norfluoxetine), FLX + NORFLX, and FLX/NORFLX. No
      relationship was found between dose-corrected FLX levels and therapeutic or
      adverse effects. No differences in serum concentrations were found between
      responders and nonresponders to treatment. Sex differences were observed in
      relation to dose and FLX serum concentration. The analysis by diagnosis revealed
      differences in FLX dose between obsessive-compulsive disorder patients and both
      generalized anxiety disorder and major depressive disorder patients. CONCLUSIONS:
      Fluoxetine response seems to be influenced by factors such as sex, diagnosis, or
      certain genes that might be involved in the drug's pharmacokinetics and
      pharmacodynamics. Clinical and pharmacogenetic studies are needed to elucidate
      further the differences between treatment responders and nonresponders.

PMID- 24743719
TI  - Sleepwalking associated with metoprolol: a case report.

PMID- 24743720
TI  - Baseline difference between patients' and clinicians' rated illness severity
      scores and subsequent outcomes in major depressive disorder: analysis of the
      sequenced treatment alternatives to relieve depression data.

PMID- 24743721
TI  - Case series of 21 synthetic cathinones abuse.

PMID- 24743722
TI  - Insomnia and morning motor vehicle accidents: a decision analysis of the risk of
      hypnotics versus the risk of untreated insomnia.

PMID- 24743723
TI  - Severe adverse drug events under combination of nortriptyline and melperone due
      to pharmacokinetic interaction.

PMID- 24743724
TI  - Two cases of sleep bruxism associated with escitalopram treatment.

PMID- 24743725
TI  - Efficacy of tadalafil on erectile dysfunction in male patients using
      antipsychotics: a double-blind, placebo-controlled, crossover pilot study.

PMID- 24743726
TI  - Sixty-Seven Consecutive Resuscitative Thoracotomies by A Single Surgeon.
AB  - BACKGROUND: Resuscitative thoracotomy is a dramatic operation performed in
      otherwise unsalvageable trauma patients. Analysis of its efficacy is based mostly
      on institutional series compiling the experience of multiple surgeons. This study
      aimed to report more consistent information by describing the resuscitative
      thoracotomy practice of a single surgeon and its evolution during more than two
      decades. METHODS: A retrospective review of consecutive patients who underwent
      resuscitative thoracotomy in July 1990 to December 2012. Demographics, mechanism
      of injury, signs of life, injuries, and outcomes were analyzed. Comparisons were
      made between penetrating and blunt trauma patients and between pre- and post
      introduction of a selective resuscitative thoracotomy protocol. RESULTS: Sixty
      seven resuscitative thoracotomies were performed. Most patients were males (84%),
      and mean age was 38 years. Mechanism of injury was stab wounds (54%, 36), blunt
      force (25%, 17), and gunshot wounds (21%, 14). Survival was 22% (8/36), 0%
      (0/17), and 7% (1/14), respectively. All nine survivors had signs of life upon
      admission, and survival in patients with signs of life on admission was 25%
      (8/32) in the stab wounds group and 8% (1/12) in the gunshot wounds group. Seven
      of the nine survivors (78%) were discharged neurologically intact. The most
      common injury in survivors was cardiac laceration with tamponade (6/9) and lung
      injury (3/9). Three survivors had a cardiac and lung injury, one had a lung hilum
      injury, and one had an abdominal inferior vena cava laceration. The switch to
      resuscitative thoracotomy protocol (2002) improved overall (31 vs 8%, p < 0.05)
      and penetrating trauma (45 vs 10%, p < 0.05) survival, eliminated resuscitative
      thoracotomy in patients presenting with no signs of life, and tended to reduce
      resuscitative thoracotomy utilization in blunt trauma patients. CONCLUSION: This
      single-surgeon series supports that resuscitative thoracotomy can be lifesaving
      in selected penetrating trauma patients in extremis. A switch to a selective
      evidence-based protocol increased overall and penetrating resuscitative
      thoracotomy survival and limited resuscitative thoracotomy performance to
      patients arriving with signs of life.

PMID- 24743727
TI  - Identification of the critical sites of NNRTI-resistance in reverse transcriptase
      of HIV-1 CRF_BC strains.
AB  - BACKGROUND: The polymorphisms involved in drug resistance to non-nucleoside
      reverse transcriptase inhibitors (NNRTIs) in HIV-1 CRF_BC, the most prevalent HIV
      1 strain in China, have been poorly characterized. RESULTS: To reveal the drug
      resistance mutations, we compared the gene sequences of pol region of HIV-1
      CRF_BC from 631 treatment-naive and 363 treatment-experienced patients using the
      selection pressure-based method. We calculated an individual Ka/Ks value for each
      specific amino acid mutation. Result showed that eight polymorphic mutations
      (W88C, K101Q, I132L, R135L, T139K/R, H221Y and L228R) in RT for treatment
      experienced patients were identified, while they, except for R135L, were
      completely absent in those from treatment-naive patients. The I132L and T139K/R
      mutants exhibited high-level resistance to DLV and NVP and moderate resistance to
      TMC-125 and EFV, while the K101Q and H221Y mutants exhibited an increased
      resistance to all four NNRTIs tested. The W88C, R135L, and L228R may be RTI
      induced adaptive mutations. Y181C+K101Q mutant showed a 2.5-, 4.4-, and 4.7-fold
      higher resistance to TMC-125, NVP and EFV, respectively, than Y181C alone mutant,
      while Y181C+H221Y or K103N+H221Y mutants had significantly higher resistance to
      all four NNRTIs than Y181C or K103N mutants. K103N+T139K and G190A+T139K mutant
      induce higher resistance (2.0~14.2-fold and 1.5~7.2-fold, respectively) to all
      four NNRTIs than K103N or G190A alone mutation. CONCLUSIONS: I132L and T139K/R
      are rare but critical mutations associated with NNRTI-resistance for some NNRTIs.
      K101Q, H221Y and T139K can enhance K103N/Y181C/G190A-assocated NNRTI-resistance.
      Monitoring these mutations will provide useful information for rational design of
      the NNRTI-based antiretroviral regimen for HIV-1 CRF_BC-infected patients.

PMID- 24743728
TI  - Beyond race and place: distal sociological determinants of HIV disparities.
AB  - Informed behavior change as an HIV prevention tool has yielded unequal successes
      across populations. Despite decades of HIV education, some individuals remain at
      high risk. The mainstream media often portrays these risk factors as products of
      race and national borders; however, a rich body of recent literature proposes a
      host of complex social factors that influence behavior, including, but not
      limited to: poverty, income inequality, stigmatizing social institutions and
      health care access. We examined the relationship between numerous social
      indicators and HIV incidence across eighty large U.S. cities in 1990 and 2000.
      During this time, major correlating factors included income inequality, poverty,
      educational attainment, residential segregation and marriage rates. However,
      these ecological factors were weighted differentially across risk groups (e.g.
      heterosexual, intravenous drug use, men who have sex with men (MSM)).
      Heterosexual risk rose significantly with poor economic indicators, while MSM
      risk depended more heavily on anti-homosexual stigma (as measured by same-sex
      marriage laws). HIV incidence among black individuals correlated significantly
      with numerous economic factors but also with segregation and imbalances in the
      male:female ratio (often an effect of mass incarceration). Our results support an
      overall model of HIV ecology where poverty, income inequality and social
      inequality (in the form of institutionalized racism and anti-homosexual stigma)
      have over time developed into synergistic drivers of disease transmission in the
      U.S., inhibiting information-based prevention efforts. The relative weights of
      these distal factors vary over time and by HIV risk group. Our testable model may
      be more generally applicable within the U.S. and beyond. 

PMID- 24743729
TI  - Coal-packed methane biofilter for mitigation of green house gas emissions from
      coal mine ventilation air.
AB  - Methane emitted by coal mine ventilation air (MVA) is a significant greenhouse
      gas. A mitigation strategy is the oxidation of methane to carbon dioxide, which
      is approximately twenty-one times less effective at global warming than methane
      on a mass-basis. The low non-combustible methane concentrations at high MVA flow
      rates call for a catalytic strategy of oxidation. A laboratory-scale coal-packed
      biofilter was designed and partially removed methane from humidified air at flow
      rates between 0.2 and 2.4 L min-1 at 30 degrees C with nutrient solution added
      every three days. Methane oxidation was catalysed by a complex community of
      naturally-occurring microorganisms, with the most abundant member being
      identified by 16S rRNA gene sequence as belonging to the methanotrophic genus
      Methylocystis. Additional inoculation with a laboratory-grown culture of
      Methylosinus sporium, as investigated in a parallel run, only enhanced methane
      consumption during the initial 12 weeks. The greatest level of methane removal of
      27.2+/-0.66 g methane m-3 empty bed h-1 was attained for the non-inoculated
      system, which was equivalent to removing 19.7+/-2.9% methane from an inlet
      concentration of 1% v/v at an inlet gas flow rate of 1.6 L min-1 (2.4 min empty
      bed residence time). These results show that low-cost coal packing holds
      promising potential as a suitable growth surface and contains methanotrophic
      microorganisms for the catalytic oxidative removal of methane. 

PMID- 24743730
TI  - Air travel is associated with intracontinental spread of dengue virus serotypes 1
      3 in Brazil.
AB  - Dengue virus and its four serotypes (DENV-1 to DENV-4) infect 390 million people
      and are implicated in at least 25,000 deaths annually, with the largest disease
      burden in tropical and subtropical regions. We investigated the spatial dynamics
      of DENV-1, DENV-2 and DENV-3 in Brazil by applying a statistical framework to
      complete genome sequences. For all three serotypes, we estimated that the
      introduction of new lineages occurred within 7 to 10-year intervals. New lineages
      were most likely to be imported from the Caribbean region to the North and
      Northeast regions of Brazil, and then to disperse at a rate of approximately 0.5
      km/day. Joint statistical analysis of evolutionary, epidemiological and
      ecological data indicates that aerial transportation of humans and/or vector
      mosquitoes, rather than Aedes aegypti infestation rates or geographical
      distances, determine dengue virus spread in Brazil. 

PMID- 24743731
TI  - Sublytic C5b-9 triggers glomerular mesangial cell apoptosis via XAF1 gene
      activation mediated by p300-dependent IRF-1 acetylation.
AB  - The apoptosis of glomerular mesangial cells (GMCs) in rat Thy-1 nephritis (Thy
      1N), a model of human mesangioproliferative glomerulonephritis (MsPGN), is
      accompanied by sublytic C5b-9 deposition. However, the mechanism by which
      sublytic C5b-9 induces GMC apoptosis is unclear. In the present studies, the
      effect of X-linked inhibitor of apoptosis-associated factor 1 (XAF1) expression
      on GMC apoptosis and the role of p300 and interferon regulatory factor-1 (IRF-1)
      in mediating XAF1 gene activation were determined, both in the GMCs induced by
      sublytic C5b-9 (in vitro) and in the renal tissues of rats with Thy-1N (in vivo).
      The in vitro studies demonstrated that IRF-1-enhanced XAF1 gene activation and
      its regulation by p300-mediated IRF-1 acetylation were involved in GMC apoptosis
      induced by sublytic C5b-9. The element of IRF-1 binding to XAF1 promoter and two
      acetylated sites of IRF-1 protein were also revealed. In vivo, silence of p300,
      IRF-1 or XAF1 genes in the renal tissues diminished GMC apoptosis and secondary
      GMC proliferation as well as urinary protein secretion in Thy-1N rats. Together,
      these data implicate that sublytic C5b-9 induces the expression of both p300 and
      IRF-1, as well as p300-dependent IRF-1 acetylation that may contribute to XAF1
      gene activation and subsequent GMC apoptosis in Thy-1N rats. 

PMID- 24743732
TI  - Salt-inducible kinase 3 is a novel mitotic regulator and a target for enhancing
      antimitotic therapeutic-mediated cell death.
AB  - Many mitotic kinases are both critical for maintaining genome stability and are
      important targets for anticancer therapies. We provide evidence that SIK3 (salt
      inducible kinase 3), an AMP-activated protein kinase-related kinase, is important
      for mitosis to occur properly in mammalian cells. Downregulation of SIK3 resulted
      in an extension of mitosis in both mouse and human cells but did not affect the
      DNA damage checkpoint. Time-lapse microscopy and other approaches indicated that
      mitotic exit but not mitotic entry was delayed. Although repression of SIK3 alone
      simply delayed mitotic exit, it was able to sensitize cells to various
      antimitotic chemicals. Both mitotic arrest and cell death caused by spindle
      poisons were enhanced after SIK3 depletion. Likewise, the antimitotic effects due
      to pharmacological inhibition of mitotic kinases including Aurora A, Aurora B,
      and polo-like kinase 1 were enhanced in the absence of SIK3. Finally, in addition
      to promoting the sensitivity of a small-molecule inhibitor of the mitotic kinesin
      Eg5, SIK3 depletion was able to overcome cells that developed drug resistance.
      These results establish the importance of SIK3 as a mitotic regulator and
      underscore the potential of SIK3 as a druggable antimitotic target. 

PMID- 24743733
TI  - Synergistic effects of glycated chitosan with high-intensity focused ultrasound
      on suppression of metastases in a syngeneic breast tumor model.
AB  - Stimulation of the host immune system is crucial in cancer treatment. In
      particular, nonspecific immunotherapies, when combined with other traditional
      therapies such as radiation and chemotherapy, may induce immunity against primary
      and metastatic tumors. In this study, we demonstrate that a novel, non-toxic
      immunoadjuvant, glycated chitosan (GC), decreases the motility and invasion of
      mammalian breast cancer cells in vitro and in vivo. Lung metastatic ratios were
      reduced in 4T1 tumor-bearing mice when intratumoral GC injection was combined
      with local high-intensity focused ultrasound (HIFU) treatment. We postulate that
      this treatment modality stimulates the host immune system to combat cancer cells,
      as macrophage accumulation in tumor lesions was detected after GC-HIFU treatment.
      In addition, plasma collected from GC-HIFU-treated tumor-bearing mice exhibited
      tumor-specific cytotoxicity. We also investigated the effect of GC on epithelial
      mesenchymal transition-related markers. Our results showed that GC decreased the
      expression of Twist-1 and Slug, proto-oncogenes commonly implicated in
      metastasis. Epithelial-cadherin, which is regulated by these genes, was also
      upregulated. Taken together, our current data suggest that GC alone can reduce
      cancer cell motility and invasion, whereas GC-HIFU treatment can induce immune
      responses to suppress tumor metastasis in vivo. 

PMID- 24743734
TI  - Impaired autophagic flux is associated with increased endoplasmic reticulum
      stress during the development of NAFLD.
AB  - The pathogenic mechanisms underlying the progression of non-alcoholic fatty liver
      disease (NAFLD) are not fully understood. In this study, we aimed to assess the
      relationship between endoplasmic reticulum (ER) stress and autophagy in human and
      mouse hepatocytes during NAFLD. ER stress and autophagy markers were analyzed in
      livers from patients with biopsy-proven non-alcoholic steatosis (NAS) or non
      alcoholic steatohepatitis (NASH) compared with livers from subjects with
      histologically normal liver, in livers from mice fed with chow diet (CHD)
      compared with mice fed with high fat diet (HFD) or methionine-choline-deficient
      (MCD) diet and in primary and Huh7 human hepatocytes loaded with palmitic acid
      (PA). In NASH patients, significant increases in hepatic messenger RNA levels of
      markers of ER stress (activating transcription factor 4 (ATF4), glucose-regulated
      protein 78 (GRP78) and C/EBP homologous protein (CHOP)) and autophagy (BCN1) were
      found compared with NAS patients. Likewise, protein levels of GRP78, CHOP and
      p62/SQSTM1 (p62) autophagic substrate were significantly elevated in NASH
      compared with NAS patients. In livers from mice fed with HFD or MCD, ER stress
      mediated signaling was parallel to the blockade of the autophagic flux assessed
      by increases in p62, microtubule-associated protein 2 light chain 3 (LC3-II)/LC3
      I ratio and accumulation of autophagosomes compared with CHD fed mice. In Huh7
      hepatic cells, treatment with PA for 8 h triggered activation of both unfolding
      protein response and the autophagic flux. Conversely, prolonged treatment with PA
      (24 h) induced ER stress and cell death together with a blockade of the
      autophagic flux. Under these conditions, cotreatment with rapamycin or CHOP
      silencing ameliorated these effects and decreased apoptosis. Our results
      demonstrated that the autophagic flux is impaired in the liver from both NAFLD
      patients and murine models of NAFLD, as well as in lipid-overloaded human
      hepatocytes, and it could be due to elevated ER stress leading to apoptosis.
      Consequently, therapies aimed to restore the autophagic flux might attenuate or
      prevent the progression of NAFLD.

PMID- 24743735
TI  - Mitochondrial proteolytic stress induced by loss of mortalin function is rescued
      by Parkin and PINK1.
AB  - The mitochondrial chaperone mortalin was implicated in Parkinson's disease (PD)
      because of its reduced levels in the brains of PD patients and disease-associated
      rare genetic variants that failed to rescue impaired mitochondrial integrity in
      cellular knockdown models. To uncover the molecular mechanisms underlying
      mortalin-related neurodegeneration, we dissected the cellular surveillance
      mechanisms related to mitochondrial quality control, defined the effects of
      reduced mortalin function at the molecular and cellular levels and investigated
      the functional interaction of mortalin with Parkin and PINK1, two PD-related
      proteins involved in mitochondrial homeostasis. We found that reduced mortalin
      function leads to: (1) activation of the mitochondrial unfolded protein response
      (UPR(mt)), (2) increased susceptibility towards intramitochondrial proteolytic
      stress, (3) increased autophagic degradation of fragmented mitochondria and (4)
      reduced mitochondrial mass in human cells in vitro and ex vivo. These alterations
      caused increased vulnerability toward apoptotic cell death. Proteotoxic
      perturbations induced by either partial loss of mortalin or chemical induction
      were rescued by complementation with native mortalin, but not disease-associated
      mortalin variants, and were independent of the integrity of autophagic pathways.
      However, Parkin and PINK1 rescued loss of mortalin phenotypes via increased
      lysosomal-mediated mitochondrial clearance and required intact autophagic
      machinery. Our results on loss of mortalin function reveal a direct link between
      impaired mitochondrial proteostasis, UPR(mt) and PD and show that effective
      removal of dysfunctional mitochondria via either genetic (PINK1 and Parkin
      overexpression) or pharmacological intervention (rapamycin) may compensate
      mitochondrial phenotypes. 

PMID- 24743736
TI  - Multiple pathways are involved in DNA degradation during keratinocyte terminal
      differentiation.
AB  - Loss of the nucleus is a critical step in keratinocyte terminal differentiation.
      To elucidate the mechanisms involved, we focused on two characteristic events:
      nuclear translocation of N-terminal fragment of profilaggrin and caspase-14
      dependent degradation of the inhibitor of caspase-activated DNase (ICAD). First,
      we demonstrated that epidermal mesotrypsin liberated a 55-kDa N-terminal fragment
      of profilaggrin (FLG-N) and FLG-N was translocated into the nucleus.
      Interestingly, these cells became TUNEL positive. Mutation in the mesotrypsin
      susceptible Arg-rich region between FLG-N and the first filaggrin domain
      abolished these changes. Furthermore, caspase-14 caused limited proteolysis of
      ICAD, followed by accumulation of caspase-activated DNase (CAD) in TUNEL-positive
      nuclei. Knockdown of both proteases resulted in a significant increase of remnant
      nuclei in a skin equivalent model. Immunohistochemical study revealed that both
      caspase-14 and mesotrypsin were markedly downregulated in parakeratotic areas of
      lesional skin from patients with atopic dermatitis and psoriasis. Collectively,
      our results indicate that at least two pathways are involved in the DNA
      degradation process during keratinocyte terminal differentiation. 

PMID- 24743737
TI  - TRPV1 activation impedes foam cell formation by inducing autophagy in oxLDL
      treated vascular smooth muscle cells.
AB  - Vascular smooth muscle cells (VSMCs) are an important origin of foam cells
      besides macrophages. The mechanisms underlying VSMC foam cell formation are
      relatively little known. Activation of transient receptor potential vanilloid
      subfamily 1 (TRPV1) and autophagy have a potential role in regulating foam cell
      formation. Our study demonstrated that autophagy protected against foam cell
      formation in oxidized low-density lipoprotein (oxLDL)-treated VSMCs; activation
      of TRPV1 by capsaicin rescued the autophagy impaired by oxLDL and activated
      autophagy-lysosome pathway in VSMCs; activation of TRPV1 by capsaicin impeded
      foam cell formation of VSMCs through autophagy induction; activation of TRPV1 by
      capsaicin induced autophagy through AMP-activated protein kinase (AMPK) signaling
      pathway. This study provides evidence that autophagy plays an important role in
      VSMC foam cell formation and highlights TRPV1 as a promising therapeutic target
      in atherosclerosis. 

PMID- 24743738
TI  - Epigenetic modification of Nrf2 in 5-fluorouracil-resistant colon cancer cells:
      involvement of TET-dependent DNA demethylation.
AB  - 5-Fluorouracil (5-FU) is a widely used anticancer drug for the treatment of
      colorectal cancer (CRC). However, resistance to 5-FU often prevents the success
      of chemotherapy. Nuclear factor-erythroid 2-related factor 2 (Nrf2) is a
      transcriptional regulator and a possible target to overcome 5-FU resistance. The
      present study examined epigenetic changes associated with Nrf2 induction in a
      human CRC cell line (SNUC5) resistant to 5-FU (SNUC5/5-FUR). Nrf2 expression,
      nuclear translocation, and binding to promoter were higher in SNUC5/5-FUR cells
      than in SNUC5 cells. The activated Nrf2 in SNUC5/5-FUR cells led to an increase
      in the protein expression and activity of heme oxygenase-1 (HO-1), an Nrf2
      regulated gene. SNUC5/5-FUR cells produced a larger amount of reactive oxygen
      species (ROS) than SNUC5 cells. The siRNA- or shRNA-mediated knockdown of Nrf2 or
      HO-1 significantly suppressed cancer cell viability and tumor growth in vitro and
      in vivo, resulting in enhanced 5-FU sensitivity. Methylation-specific (MS) or
      real-time quantitative MS-PCR data showed hypomethylation of the Nrf2 promoter
      CpG islands in SNUC5/5-FUR cells compared with SNUC5 cells. Expression of the DNA
      demethylase ten-eleven translocation (TET) was upregulated in SNUC5/5-FUR cells.
      ROS generated by 5-FU upregulated TET1 expression and function, whereas
      antioxidant had the opposite effect. These results suggested that the mechanism
      underlying the acquisition of 5-FU resistance in CRC involves the upregulation of
      Nrf2 and HO-1 expression via epigenetic modifications of DNA demethylation. 

PMID- 24743739
TI  - Selective 14-3-3gamma induction quenches p-beta-catenin Ser37/Bax-enhanced cell
      death in cerebral cortical neurons during ischemia.
AB  - Ischemia-induced cell death is a major cause of disability or death after stroke.
      Identifying the key intrinsic protective mechanisms induced by ischemia is
      critical for the development of effective stroke treatment. Here, we reported
      that 14-3-3gamma was a selective ischemia-inducible survival factor in cerebral
      cortical neurons reducing cell death by downregulating Bax depend direct 14-3
      3gamma/p-beta-catenin Ser37 interactions in the nucleus. 14-3-3gamma, but not
      other 14-3-3 isoforms, was upregulated in primary cerebral cortical neurons upon
      oxygen-glucose deprivation (OGD) as measured by quantitative PCR, western blot
      and fluorescent immunostaining. The selective induction of 14-3-3gamma in
      cortical neurons by OGD was verified by the in vivo ischemic stroke model.
      Knocking down 14-3-3gamma alone or inhibiting 14-3-3/client interactions was
      sufficient to induce cell death in normal cultured neurons and exacerbate OGD
      induced neuronal death. Ectopic overexpression of 14-3-3gamma significantly
      reduced OGD-induced cell death in cultured neurons. Co-immunoprecipitation and
      fluorescence resonance energy transfer demonstrated that endogenous 14-3-3gamma
      bound directly to more p-beta-catenin Ser37 but not p-Bad, p-Ask-1, p-p53 and
      Bax. During OGD, p-beta-catenin Ser37 but not p-beta-catenin Ser45 was increased
      prominently, which correlated with Bax elevation in cortical neurons. OGD
      promoted the entry of 14-3-3gamma into the nuclei, in correlation with the
      increase of nuclear p-beta-catenin Ser37 in neurons. Overexpression of 14-3
      3gamma significantly reduced Bax expression, whereas knockdown of 14-3-3gamma
      increased Bax in cortical neurons. Abolishing beta-catenin phosphorylation at
      Ser37 (S37A) significantly reduced Bax and cell death in neurons upon OGD.
      Finally, 14-3-3gamma overexpression completely suppressed beta-catenin-enhanced
      Bax and cell death in neurons upon OGD. Based on these data, we propose that the
      14-3-3gamma/p-beta-catenin Ser37/Bax axis determines cell survival or death of
      neurons during ischemia, providing novel therapeutic targets for ischemic stroke
      as well as other related neurological diseases. 

PMID- 24743740
TI  - Agonist antibodies activating the Met receptor protect cardiomyoblasts from
      cobalt chloride-induced apoptosis and autophagy.
AB  - Met, the tyrosine kinase receptor for hepatocyte growth factor (HGF), mainly
      activates prosurvival pathways, including protection from apoptosis. In this
      work, we investigated the cardioprotective mechanisms of Met activation by
      agonist monoclonal antibodies (mAbs). Cobalt chloride (CoCl2), a chemical mimetic
      of hypoxia, was used to induce cardiac damage in H9c2 cardiomyoblasts, which
      resulted in reduction of cell viability by (i) caspase-dependent apoptosis and
      (ii) - surprisingly - autophagy. Blocking either apoptosis with the caspase
      inhibitor benzyloxycarbonyl-VAD-fluoromethylketone or autophagosome formation
      with 3-methyladenine prevented loss of cell viability, which suggests that both
      processes contribute to cardiomyoblast injury. Concomitant treatment with Met
      activating antibodies or HGF prevented apoptosis and autophagy. Pro-autophagic
      Redd1, Bnip3 and phospho-AMPK proteins, which are known to promote autophagy
      through inactivation of the mTOR pathway, were induced by CoCl2. Mechanistically,
      Met agonist antibodies or HGF prevented the inhibition of mTOR and reduced the
      flux of autophagosome formation. Accordingly, their anti-autophagic function was
      completely blunted by Temsirolimus, a specific mTOR inhibitor. Targeted Met
      activation was successful also in the setting of low oxygen conditions, in which
      Met agonist antibodies or HGF demonstrated anti-apoptotic and anti-autophagic
      effects. Activation of the Met pathway is thus a promising novel therapeutic tool
      for ischaemic injury. 

PMID- 24743741
TI  - Identification and characterization of PDGFRalpha+ mesenchymal progenitors in
      human skeletal muscle.
AB  - Fatty and fibrous connective tissue formation is a hallmark of diseased skeletal
      muscle and deteriorates muscle function. We previously identified non-myogenic
      mesenchymal progenitors that contribute to adipogenesis and fibrogenesis in mouse
      skeletal muscle. In this study, we report the identification and characterization
      of a human counterpart to these progenitors. By using PDGFRalpha as a specific
      marker, mesenchymal progenitors can be identified in the interstitium and
      isolated from human skeletal muscle. PDGFRalpha(+) cells represent a cell
      population distinct from CD56(+) myogenic cells, and adipogenic and fibrogenic
      potentials were highly enriched in the PDGFRalpha(+) population. Activation of
      PDGFRalpha stimulates proliferation of PDGFRalpha(+) cells through PI3K-Akt and
      MEK2-MAPK signaling pathways, and aberrant accumulation of PDGFRalpha(+) cells
      was conspicuous in muscles of patients with both genetic and non-genetic muscle
      diseases. Our results revealed the pathological relevance of PDGFRalpha(+)
      mesenchymal progenitors to human muscle diseases and provide a basis for
      developing therapeutic strategy to treat muscle diseases. 

PMID- 24743742
TI  - Opposing TNF-alpha/IL-1beta- and BMP-2-activated MAPK signaling pathways converge
      on Runx2 to regulate BMP-2-induced osteoblastic differentiation.
AB  - In patients who were treated with exogenous BMP-2 to repair bone fractures or
      defects, the levels of the inflammatory cytokines such as TNF-alpha and IL-1beta
      in sera are significantly elevated, which may affect the outcome of bone
      regeneration. Mitogen-activated protein kinase (MAPK) cascades such as
      extracellular signal-regulated kinase 1/2 (ERK1/2), p38, and c-Jun NH2-terminal
      kinase 1/2 (JNK1/2) have a crucial role in osteogenic differentiation and are
      activated by both BMP-2 and TNF-alpha/IL-1beta. However, previous studies
      suggested that the effects of BMP-2 and TNF-alpha/IL-1beta in osteoblastic
      differentiation are opposite. Here, we investigated the exact role of MAPKs in a
      BMP-2 and TNF-alpha/IL-1beta co-existed condition. Treatment with TNF-alpha/IL
      1beta inhibited BMP-2-induced alkaline phosphatase activity, calcium deposition,
      osteogenic transcriptional factor Runx2, and the expression of osteogenic markers
      in C2C12 and MC3T3-E1 cells. This inhibitory effect was independent of the
      canonical BMP/Smad pathway, suggesting the presence of an alternate regulatory
      pathway for BMP-2-induced Runx2 activity and subsequent osteoblastic
      differentiation. We then confirmed that BMP-2, TNF-alpha, and IL-1beta alone can
      activate p38, ERK1/2, and JNK1/2, respectively. However, only inhibition of p38
      and ERK1/2 signaling were required to modulate BMP-2-induced Runx2 expression.
      Finally, we determined that TNF-alpha/IL-1beta decreased BMP-2-induced Runx2
      expression through the activation of p38 and ERK1/2 signaling. Furthermore,
      strong activation of p38 and ERK1/2 signaling by transfection with CA-MKK3 or CA
      MEK1 inhibited BMP-2-induced Runx2 expression and osteoblastic differentiation in
      C2C12 and MC3T3-E1 cells. Based on these results, we conclude that TNF-alpha/IL
      1beta- and BMP-2-activated p38 and ERK1/2 signaling have opposing roles that
      converge on Runx2 to regulate osteoblastic differentiation. The elucidation of
      these mechanisms may hasten the development of new strategies and improve the
      osteoinductive efficacy of BMP-2 in the clinic to enhance osteoblastic
      differentiation and bone formation.

PMID- 24743743
TI  - Reduced IRE1alpha mediates apoptotic cell death by disrupting calcium homeostasis
      via the InsP3 receptor.
AB  - The endoplasmic reticulum (ER) is not only a home for folding and
      posttranslational modifications of secretory proteins but also a reservoir for
      intracellular Ca(2+). Perturbation of ER homeostasis contributes to the
      pathogenesis of various neurodegenerative diseases, such as Alzheimer's and
      Parkinson diseases. One key regulator that underlies cell survival and Ca(2+)
      homeostasis during ER stress responses is inositol-requiring enzyme 1alpha
      (IRE1alpha). Despite extensive studies on this ER membrane-associated protein,
      little is known about the molecular mechanisms by which excessive ER stress
      triggers cell death and Ca(2+) dysregulation via the IRE1alpha-dependent
      signaling pathway. In this study, we show that inactivation of IRE1alpha by RNA
      interference increases cytosolic Ca(2+) concentration in SH-SY5Y cells, leading
      to cell death. This dysregulation is caused by an accelerated ER-to-cytosolic
      efflux of Ca(2+) through the InsP3 receptor (InsP3R). The Ca(2+) efflux in
      IRE1alpha-deficient cells correlates with dissociation of the Ca(2+)-binding
      InsP3R inhibitor CIB1 and increased complex formation of CIB1 with the pro
      apoptotic kinase ASK1, which otherwise remains inactivated in the IRE1alpha-TRAF2
      ASK1 complex. The increased cytosolic concentration of Ca(2+) induces
      mitochondrial production of reactive oxygen species (ROS), in particular
      superoxide, resulting in severe mitochondrial abnormalities, such as
      fragmentation and depolarization of membrane potential. These Ca(2+)
      dysregulation-induced mitochondrial abnormalities and cell death in IRE1alpha
      deficient cells can be blocked by depleting ROS or inhibiting Ca(2+) influx into
      the mitochondria. These results demonstrate the importance of IRE1alpha in Ca(2+)
      homeostasis and cell survival during ER stress and reveal a previously unknown
      Ca(2+)-mediated cell death signaling between the IRE1alpha-InsP3R pathway in the
      ER and the redox-dependent apoptotic pathway in the mitochondrion. 

PMID- 24743744
TI  - Serum free fatty acid biomarkers of lung cancer.
AB  - BACKGROUND: Lung cancer is the leading cause of cancer-related mortality.
      Surgical removal of the tumor at an early stage can be curative. However, lung
      cancer diagnosis at an early stage remains challenging. There is evidence that
      free fatty acids play a role in cancer development. METHODS: Serum samples from
      55 patients with lung cancer were propensity matched with samples from 165
      similar pulmonary patients without known cancer. Patients were propensity matched
      on age, sex, smoking history, family history of lung cancer, and chronic diseases
      that might affect free fatty acid levels. RESULTS: Free fatty acids arachidonic
      acid (AA) and linoleic acid (LA) and their metabolites hydroxyeicosatetraenoic
      acids (HETEs)(5-HETE, 11-HETE, 12-HETE, and 15-HETE) were an estimated 1.8- to
      3.3-fold greater in 37 patients with adenocarcinoma vs 111 patients without
      cancer (all P < .001). Areas under the receiver operating characteristic curve
      were significantly > 0.50, discriminating patients with lung cancer and control
      subjects for six of eight biomarkers and two of seven phospholipids tested, and
      ranged between 0.69 and 0.82 (all P < .001) for patients with lung cancer vs
      control subjects. AA, LA, and 15-HETE had observed sensitivity and specificity >
      0.70 at the best cutpoint. Concentrations of free fatty acids and their
      metabolites were similar in 18 patients with squamous cell carcinoma and 54
      control subjects without cancer. CONCLUSIONS: Serum fatty acids and their
      metabolites demonstrate good sensitivity and specificity for the identification
      of adenocarcinoma of the lung.

PMID- 24743745
TI  - The melanogenesis alteration effects of Achillea millefolium L. essential oil and
      linalyl acetate: involvement of oxidative stress and the JNK and ERK signaling
      pathways in melanoma cells.
AB  - The mitogen-activated protein kinase (MAPK) family, including extracellular
      signal-regulated kinase (ERK)1/2, c-Jun N-terminal kinase (JNK)1/2 and p38 MAPK,
      is known to be activated by ultraviolet (UV) radiation in melanocytes to regulate
      melanin production. Reactive oxygen species (ROS) play important roles in the
      pathway of ERK and JNK activation. It has been established that the essential oil
      of Achillea millefolium L. (AM-EO) has activities that suppress the oxidative
      stress and inflammatory responses. Thus, we analyzed the effects of AM-EO on
      melanogenesis in melanocyte stimulating hormone (alpha-MSH) treated melanoma
      cells. The results demonstrated that AM-EO suppresses melanin production by
      decreasing tyrosinase activity through the regulation of the JNK and ERK
      signaling pathways. This effect might be associated with the AM-EO activity
      leading to the suppression of ROS, and linalyl acetate is its major functional
      component. Therefore, we propose that AM-EO has the potential to treat
      hyperpigmentation in the future. 

PMID- 24743746
TI  - Exploring the effect of asymmetric mitochondrial DNA introgression on estimating
      niche divergence in morphologically cryptic species.
AB  - If potential morphologically cryptic species, identified based on differentiated
      mitochondrial DNA, express ecological divergence, this increases support for
      their treatment as distinct species. However, mitochondrial DNA introgression
      hampers the correct estimation of ecological divergence. We test the hypothesis
      that estimated niche divergence differs when considering nuclear DNA composition
      or mitochondrial DNA type as representing the true species range. We use
      empirical data of two crested newt species (Amphibia: Triturus) which possess
      introgressed mitochondrial DNA from a third species in part of their ranges. We
      analyze the data in environmental space by determining Fisher distances in a
      principal component analysis and in geographical space by determining
      geographical overlap of species distribution models. We find that under mtDNA
      guidance in one of the two study cases niche divergence is overestimated, whereas
      in the other it is underestimated. In the light of our results we discuss the
      role of estimated niche divergence in species delineation. 

PMID- 24743747
TI  - A Huge Morel-Lavallee Lesion Treated Using a Quilting Suture Method: A Case
      Report and Review of the Literature.
AB  - The Morel-Lavallee lesion is a collection of serous fluid that develops after
      closed degloving injuries and after surgical procedures particularly in the
      pelvis and abdomen. It is a persistent seroma and is usually resistant to
      conservative methods of treatment such as percutaneous drainage and compression.
      Various methods of curative treatment have been reported in the literature, such
      as application of fibrin sealant, doxycycline, or alcohol sclerodhesis. We
      present a case of a huge recurrent Morel-Lavallee lesion in the lower back and
      buttock region that was treated with quilting sutures, fibrin sealant, and
      compression, with a review of the literature.

PMID- 24743748
TI  - Genetic Alterations in Toll-Like Receptor 4 Signaling Pathway and Impairment of
      Wound Healing in Patients With Type 2 Diabetes.

PMID- 24743749
TI  - Bosentan and Extracorporeal Photochemotherapy in Eosinophilic Fasciitis:
      Synergistic Action or Fortuitous Coincidence?

PMID- 24743750
TI  - Successful Treatment of a Patient With Complicated Diabetic Foot Wound: A Case
      Report.
AB  - Foot ulceration is one of the most serious complications of diabetes mellitus and
      may lead to amputation of the lower extremity. Timely prophylaxis and treatment
      of diabetic foot ulceration are important to maintain a good quality of life.
      This article reports a complicated diabetic patient with severe limb-threatening
      necrotizing infection. We successfully applied endovascular stent insertion,
      digit amputation, negative pressure wound therapy, and advanced dressings in
      different wound phases to achieve definitive wound healing after 12 months of
      treatment. Based on this case report, we would like to emphasize the importance
      of combined multiple therapies and patient compliance for severe diabetic foot
      ulcers.

PMID- 24743751
TI  - Reliability of ultrasound imaging for the assessment of lumbar multifidi
      thickness in older adults with chronic low back pain.
AB  - BACKGROUND AND PURPOSE: Ultrasound imaging (USI) has been shown to be a reliable
      measure for direct assessment of the lumbar multifidi among younger adults.
      However, given age- and chronic low back pain (CLBP)-related spinal changes,
      similar studies are needed before clinical use of USI among older adults with
      CLBP. The goals of this study were to evaluate intra- and interexaminer
      reliability for USI assessment of multifidi thickness at rest and during a
      contraction and to determine standard error of measurement values (SEMs) and
      minimal detectable change values (MDCs) among older adults with CLBP. METHODS:
      Thirty-one adults, aged 60 to 85 years, with CLBP were recruited. Two examiners
      performed USI assessments of multifidus thickness at rest and during a
      contralateral lower extremity lift. Intraclass correlation coefficients (ICCs)
      were used to estimate inter- and intraexaminer reliability. Additionally, SEMs
      and MDCs were calculated. RESULTS: All USI measurement techniques demonstrated
      excellent within-day, interexaminer procedural reliability (ICCs: 0.82-0.85) and
      good-to-excellent between-day, interexaminer procedural reliability (ICCs: 0.72
      0.79). The SEMs ranged from 0.36 to 0.46 cm; MDCs ranged from 1.01 to 1.26 cm.
      Regardless of the measurement technique, examiner 1, the more experienced
      examiner, demonstrated lower SEMs and MDCs than examiner 2. DISCUSSION: Lower
      ICCs, greater SEMs, and greater MDCs for USI multifidus thickness assessment in
      older adults with CLBP, when compared with previously published, procedural
      reliability results for younger adults with and without low back pain, may
      indicate that imaging is more challenging in this patient population. Factors,
      such as examiner training and participant anthropometrics, may impact
      reliability. CONCLUSIONS: Good-to-excellent intra- and interexaminer USI
      procedural reliability may provide clinicians a direct assessment technique for
      clinical evaluation of the lumbar multifidi in older adults with CLBP. SEMs and
      MDCs may allow for accurate interpretation of USI assessments in this population.

PMID- 24743752
TI  - Comparative effects of 2 aqua exercise programs on physical function, balance,
      and perceived quality of life in older adults with osteoarthritis.
AB  - BACKGROUND: Osteoarthritis (OA) is a degenerative joint disease, which affects a
      large number of older adults. Many older adults with OA are physically inactive,
      which can contribute to reduced functional capability, quality of life, and an
      increased risk of falls. Although hydrotherapy is often recommended for older
      adults with OA, less is known about aqua fitness (AF), a widely available form of
      aqua-based exercise. PURPOSE: To compare the effect of an AF program and a seated
      aqua-based exercise program on a range of functional measures and quality of life
      among older adults with OA. METHODS: Thirty-five older adults with OA were
      allocated to an AF group or an active control group who performed seated
      exercises in warm water for 12 weeks. The primary outcome measure was the timed
      up-and-go (TUG) test; other measures included step test, sit-to-stand (STS) test,
      handgrip strength test, 400-m walk test, Arthritis Impact Measurement Scale-Short
      Form (AIMS2-SF), and Falls Efficacy Scale-International (FES-I). RESULTS: FES-I
      scores improved significantly in the AF group compared with the control group
      (P=0.04). Within-group analysis indicated both groups significantly improved
      their 400-m walk time (P=0.04) and that the AF group significantly improved its
      step test right (P=0.02) and left (P=0.00) and the AIMS2-SF total score (P=0.02).
      No significant change in TUG, STS, or handgrip strength was observed for either
      group. CONCLUSIONS: Aqua fitness may offer a number of positive functional and
      psychosocial benefits for older adults with OA, such as a reduced fear of falling
      and increased ability to perform everyday tasks.

PMID- 24743753
TI  - Biophysical modelling of the effects of inhaled radon progeny on the bronchial
      epithelium for the estimation of the relationships applied in the two-stage
      clonal expansion model of carcinogenesis.
AB  - There is a considerable debate between research groups applying the two-stage
      clonal expansion model for lung cancer risk estimation, whether radon exposure
      affects initiation and transformation or promotion. The aim of the present study
      is to quantify the effects of radon progeny on these stages with biophysical
      models. For this purpose, numerical models of mutation induction and clonal
      growth were applied in order to estimate how initiation, transformation and
      promotion rates depend on tissue dose rate. It was found that rates of initiation
      and transformation increase monotonically with dose rate, whereas effective
      promotion rate decreases with time but increases sublinearly with dose rate.
      Despite the uncertainty of results due to the lack of experimental data, present
      study suggests that effects of radon exposure on both mutational events and
      clonal growth are significant and should be considered in mechanistic models of
      carcinogenesis applied for analysing epidemiological data. 

PMID- 24743754
TI  - General guidelines for safe and expeditious international transport of samples
      subjected to biological dosimetry assessment.
AB  - It has been observed that victims of accidental overexposures show better chance
      of survival if they receive medical treatment early. The increased risk of
      scenarios involving mass casualties has stimulated the scientific community to
      develop tools that would help the medical doctors to treat victims. The
      biological dosimetry has become a routine test to estimate the dose,
      supplementing physical and clinical dosimetry. In case of radiation emergencies,
      in order to provide timely and effectively biological dosimetry assistance it is
      essential to guarantee an adequate transport of blood samples in principal, for
      providing support to countries that do not have biodosimetry laboratories. The
      objective of the present paper is to provide general guidelines, summarised in 10
      points, for timely and proper receiving and sending of blood samples under
      National and International regulations, for safe and expeditious international
      transport. These guidelines cover the classification, packaging, marking,
      labelling, refrigeration and documentation requirements for the international
      shipping of blood samples and pellets, to provide assistance missions with a tool
      that would contribute with the preparedness for an effective biodosimetric
      response in cases of radiological or nuclear emergencies. 

PMID- 24743756
TI  - A novel parameter, cell-cycle progression index, for radiation dose absorbed
      estimation in the premature chromosome condensation assay.
AB  - The calyculin A-induced premature chromosome condensation (PCC) assay is a simple
      and useful method for assessing the cell-cycle distribution in cells, since
      calyculin A induces chromosome condensation in various phases of the cell cycle.
      In this study, a novel parameter, the cell-cycle progression index (CPI), in the
      PCC assay was validated as a novel biomarker for biodosimetry. Peripheral blood
      was drawn from healthy donors after informed consent was obtained. CPI was
      investigated using a human peripheral blood lymphocyte (PBL) ex vivo irradiation
      ((60)Co-gamma rays: ~0.6 Gy min(-1), or X ray: 1.0 Gy min(-1); 0-10 Gy) model.
      The calyculin A-induced PCC assay was performed for chromosome preparation. PCC
      cells were divided into the following five categories according to cell-cycle
      stage: non-PCC, G1-PCC, S-PCC, G2/M-PCC and M/A-PCC cells. CPI was calculated as
      the ratio of G2/M-PCC cells to G1-PCC cells. The PCC-stage distribution varied
      markedly with irradiation doses. The G1-PCC cell fraction was significantly
      reduced, and the G2/M-PCC cell fraction increased, in 10-Gy-irradiated PBL after
      48 h of culture. CPI levels were fitted to an exponential dose-response curve
      with gamma-ray irradiation [y = 0.6729 + 0.3934 exp(0.5685D), r = 1.0000, p <
      0.0001] and X-ray irradiation [y = -0.3743 + 0.9744 exp(0.3321D), r = 0.9999, p <
      0.0001]. There were no significant individual (p = 0.853) or gender effects (p =
      0.951) on the CPI in the human peripheral blood ex vivo irradiation model.
      Furthermore, CPI measurements are rapid (< 15 min per case). These results
      suggest that the CPI is a useful screening tool for the assessment of radiation
      doses received ranging from 0 to 10 Gy in radiation exposure early after a
      radiation event, especially after a mass-casualty radiological incident. 

PMID- 24743755
TI  - Parameter uncertainty analysis of a biokinetic model of caesium.
AB  - Parameter uncertainties for the biokinetic model of caesium (Cs) developed by
      Leggett et al. were inventoried and evaluated. The methods of parameter
      uncertainty analysis were used to assess the uncertainties of model predictions
      with the assumptions of model parameter uncertainties and distributions.
      Furthermore, the importance of individual model parameters was assessed by means
      of sensitivity analysis. The calculated uncertainties of model predictions were
      compared with human data of Cs measured in blood and in the whole body. It was
      found that propagating the derived uncertainties in model parameter values
      reproduced the range of bioassay data observed in human subjects at different
      times after intake. The maximum ranges, expressed as uncertainty factors (UFs)
      (defined as a square root of ratio between 97.5th and 2.5th percentiles) of blood
      clearance, whole-body retention and urinary excretion of Cs predicted at earlier
      time after intake were, respectively: 1.5, 1.0 and 2.5 at the first day; 1.8, 1.1
      and 2.4 at Day 10 and 1.8, 2.0 and 1.8 at Day 100; for the late times (1000 d)
      after intake, the UFs were increased to 43, 24 and 31, respectively. The model
      parameters of transfer rates between kidneys and blood, muscle and blood and the
      rate of transfer from kidneys to urinary bladder content are most influential to
      the blood clearance and to the whole-body retention of Cs. For the urinary
      excretion, the parameters of transfer rates from urinary bladder content to urine
      and from kidneys to urinary bladder content impact mostly. The implication and
      effect on the estimated equivalent and effective doses of the larger uncertainty
      of 43 in whole-body retention in the later time, say, after Day 500 will be
      explored in a successive work in the framework of EURADOS. 

PMID- 24743757
TI  - Radon soil gas measurements in a geological versatile region as basis to improve
      the prediction of areas with a high radon potential.
AB  - With the aim to predict the radon potential by geological data, radon soil gas
      measurements were made in a selected region in Styria, Austria. This region is
      characterised by mean indoor radon potentials of 130-280 Bq m(-3) and a high
      geological diversity. The distribution of the individual measuring sites was
      selected on the basis of geological aspects and the distribution of area
      settlements. In this work, the radon soil gas activity concentration and the soil
      permeability were measured at 100 sites, each with three single measurements.
      Furthermore, the local dose rate was determined and soil samples were taken at
      each site to determine the activity concentration of natural radionuclides.
      During two investigation periods, long-term soil gas radon measurements were made
      to study the time dependency of the radon activity concentration. All the results
      will be compared and investigated for correlation among each other to improve the
      prediction of areas with high radon potential. 

PMID- 24743758
TI  - Diurnal and seasonal variability of outdoor radon concentration in the area of
      the NRPI Prague.
AB  - In autumn 2010, an outdoor measuring station for measurement of atmospheric
      radon, gamma equivalent dose rate in the range of 100 nSv h(-1)-1 Sv h(-1) and
      proper meteorological parameters such as thermal air gradient, relative air
      humidity, wind speed and direction and solar radiation intensity was built in the
      area of the National Radiation Protection Institute vvi. The station was designed
      to be independent of an electrical network and enables on-line wireless transfer
      of all data. After introduction of the station, illustrations of its measurement
      properties and the results of measured diurnal and seasonal variability of
      atmospheric radon, based on annual continuous measurement using a high-volume
      scintillation cell at a height of 2.5 m above the ground, are presented. 

PMID- 24743759
TI  - Influence of energy-saving measures on the radon concentration in some
      kindergartens in the Czech Republic.
AB  - Due to the large number of subsidies for energy-saving reconstructions granted,
      and expecting a strong influence of reconstruction on the radon level in
      building, the long-term measurements of radon concentration are offered free of
      charge to kindergartens in the Czech Republic. Classrooms and playrooms where the
      radon levels exceeded the reference value for kindergartens, which is 400 Bq m(
      3), are monitored continuously for at least a week to obtain the average activity
      concentration of radon when children are present. Some of the kindergartens were
      previously measured in the 1990s. These earlier measurements have provided an
      opportunity to compare the results. This paper presents some lessons learned from
      radon diagnosis carried out in particular cases and an analysis of the influence
      of reconstruction work on the radon level in the buildings. 

PMID- 24743760
TI  - FISH analysis of translocations induced by chronic exposure to Sr radioisotopes:
      second set of analysis of the Techa River Cohort.
AB  - Fluorescent in situ hybridisation analysis of stable translocations was performed
      for 26 residents living along the Techa River (Russia), who were predominantly
      (95%) exposed to ingested strontium radioisotopes ((89)Sr and (90)Sr) resulting
      in exposure of their red bone marrow (RBM). Analysis was conducted at the Urals
      Research Center for Radiation Medicine, Public Health England and Leiden
      University Medical Center. Each laboratory scored 1000 cells per donor, which
      resulted in ~1000 genome equivalents (GE) per donor. The age-dependent
      spontaneous level of translocations for each donor was evaluated on the basis of
      data published by Sigurdson et al. (International study of factors affecting
      human chromosome. Mutat. Res. 2008;652: :112-121). Reconstruction of doses was
      performed with the 'Techa River Dosimetry System' developed in 2009. In the
      studied donors, the range of individual cumulated RBM dose was from 0.3 to 3.7
      Gy. Analysis of the yield of stable translocations dependent on the individual
      RBM dose from (89,90)Sr showed a linear dose-response relationship of 0.007 +/-
      0.002 translocation/GE cell/Gy (R = 0.61, p = 0.001). This set of results was in
      a good agreement with the previous data reported for 18 donors by Vozilova et al.
      (Preliminary FISH-based assessment of external dose for residents exposed on the
      Techa River.

PMID- 24743761
TI  - Reducing the risks from radon indoors: an IAEA perspective.
AB  - The IAEA has a mandate to develop, in collaboration with other relevant
      international organisations, 'standards of safety for protection of health and
      minimisation of danger to life and property', and to provide for the application
      of these standards. The most recent edition of the International Basic Safety
      Standards includes, for the first time, requirements to protect the public from
      exposure due to radon indoors. As a result, the IAEA has already developed
      guidance material in line with accepted best international practice and an
      international programme to assist its Member States in identifying and addressing
      high radon concentrations in buildings is being prepared. This paper overviews
      the current situation around the world and summarises the management approach
      advocated by the IAEA. A number of important scientific and policy issues are
      identified and discussed from the point-of-view of how they may impact on
      national action plans and strategies. Finally, the assistance and support
      available through the Agency is described. 

PMID- 24743762
TI  - Analysis of problems and failures in the measurement of soil-gas radon
      concentration.
AB  - Long-term experience in the field of soil-gas radon concentration measurements
      allows to describe and explain the most frequent causes of failures, which can
      appear in practice when various types of measurement methods and soil-gas
      sampling techniques are used. The concept of minimal sampling depth, which
      depends on the volume of the soil-gas sample and on the soil properties, is shown
      in detail. Consideration of minimal sampling depth at the time of measurement
      planning allows to avoid the most common mistakes. The ways how to identify
      influencing parameters, how to avoid a dilution of soil-gas samples by the
      atmospheric air, as well as how to recognise inappropriate sampling methods are
      discussed. 

PMID- 24743763
TI  - Radiation-induced defects in manganese-doped lithium tetraborate phosphor.
AB  - Lithium tetraborate doped with manganese synthesised by solid-state sintering
      technique exhibits a dosimetric peak at 280 degrees C. The high-temperature glow
      curve results in no fading for three months. The sensitivity of Li2B4O7:Mn is
      determined to be 0.9 times that of TLD-100. The infrared spectrum of this
      phosphor indicates the presence of bond vibrations corresponding to BO4
      tetrahedral and BO3 triangles. The mechanism for thermoluminescence in this
      phosphor was proposed based on the thermoluminescence (TL) emission spectra,
      kinetic analysis of TL glow curves and electron paramagnetic resonance (EPR)
      measurements on non-irradiated and gamma-irradiated phosphors. It was identified
      that oxygen vacancies and Boron oxygen hole centre (BOHC) are the electron and
      hole trap centres for TL in this phosphor. When the phosphor is heated, the
      electrons are released from the electron trap and recombine with the trapped
      holes. The excitation energy during the recombination is transferred to the
      nearby Mn(2+) ions, which emit light at 580 nm. 

PMID- 24743764
TI  - Thoron and thoron progeny measurements in German clay houses.
AB  - In recent years, elevated thoron concentrations were found in houses built of
      unfired clay. In this study experiments were carried out in 17 traditional and
      modern clay houses in Germany to obtain an overview of indoor thoron in such
      houses. Long-term measurements over an 8-week period were performed using a newly
      developed Unattended Battery-Operated Progeny Measurement Device (UBPM) for
      measuring thoron progeny. This instrument uses a high-voltage electric field to
      precipitate radon and thoron progeny on nuclear track detectors. Additional
      active and passive measurements of radon, thoron and their progeny were
      performed. The equilibrium equivalent thoron concentration was found to be
      between 2 and 10 Bq m(-3). Gas concentrations were found to be between 20 and 160
      Bq m(-3) for radon and between 10 and 90 Bq m(-3) for thoron 20 cm from the wall.
      The thoron exposure contributes significantly to the inhalation dose of the
      dwellers (0.6-4 mSv a(-1)). 

PMID- 24743765
TI  - Improving the uncertainty on short-term radon measurements using PADC detector.
AB  - Radon measurements over a short-term period of a few days have proven a popular
      choice with the general public, despite the issue that the radon concentration
      can vary significantly over time and longer periods of integration are
      recommended. Performing short-term radon measurements using a Poly Allyl Diglycol
      Carbonate (PADC) detector would see a larger contribution from the statistical
      error associated with the measurements than for longer term measurements. This
      motivated the investigation to improve the uncertainty on short-term measurements
      by utilising a new formulation of high-sensitivity PADC and also by investigating
      the effect of increasing the scan area and extending the measurement time by just
      a few days. 

PMID- 24743766
TI  - An evaluation of thoron (and radon) equilibrium factor close to walls based on
      long-term measurements in dwellings.
AB  - Thoron gas and its progeny behave quite differently in room environments, owing
      to the difference in their half-lives; therefore, it is important to measure
      simultaneously gas and progeny concentrations to estimate the time-integrated
      equilibrium factor. Furthermore, thoron concentration strongly depends on the
      distance from the source, i.e. generally walls in indoor environments. In the
      present work, therefore, the measurements of both thoron and radon gas and their
      progeny concentrations were consistently carried out close to the walls, in 43
      dwellings located in the Sokobanja municipality, Serbia. Three different types of
      instruments have been used in the present survey to measure the time-integrated
      thoron and radon gas and their progeny concentrations simultaneously. The
      equilibrium factor for thoron measured 'close to the wall', [Formula: see text],
      ranged from 0.001 to 0.077 with a geometric mean (GM) [geometric standard
      deviation (GSD)] of 0.006 (2.2), whereas the equilibrium factor for radon, FRn,
      ranged from 0.06 to 0.95 with a GM (GSD) of 0.23 (2.0). 

PMID- 24743767
TI  - Is a semi-automated approach indicated in the application of the automated
      micronucleus assay for triage purposes?
AB  - Within the EU MULTIBIODOSE project, the automated micronucleus (MN) assay was
      optimised for population triage in large-scale radiological emergencies. For MN
      scoring, two approaches were applied using the Metafer4 platform (MetaSystems,
      Germany): fully automated scoring and semi-automated scoring with visual
      inspection of the gallery of MN-positive objects. Dose-response curves were
      established for acute and protracted whole-body and partial-body exposures. A
      database of background MN yields was set up, allowing determination of the dose
      detection threshold in both scoring modes. An analysis of the overdispersion of
      the MN frequency distribution sigma(2)/u obtained by semi-automated scoring
      showed that the value of this parameter represents a reliability check of the
      calculated equivalent total body dose in case the accident overexposure is a
      partial-body exposure. The elaborated methodology was validated in an accident
      training exercise. Overall, the semi-automated scoring procedure represents
      important added value to the automated MN assay. 

PMID- 24743768
TI  - Towards a Brazilian radon map: consortium radon Brazil.
AB  - Recently, the idea of generating radon map of Brazil has emerged. First attempts
      of coordinating radon surveys--carried out by different groups across the country
      -and initial discussions on how to proceed on a larger scale were made at the
      First Brazilian Radon Seminary, Natal, September 2012. Conventionally, it is
      believed that indoor radon is no major problem in Brazil, because the overall
      benign climate usually allows high ventilation rates. Nevertheless, scattered
      measurements have shown that moderately high indoor radon concentrations (up to a
      few hundred Bq m-3) do occur regionally. Brazilian geology is very diverse and
      there are regions where an elevated geogenic radon potential exists or is
      expected to exist. Therefore, a Brazilian Radon Survey is expected to be a
      challenge, although it appears an important issue, given the rising concern of
      the public about the quality of its environment.

PMID- 24743769
TI  - Generation and characterization of a mouse model harboring the exon-3 deletion in
      the cardiac ryanodine receptor.
AB  - A large genomic deletion in human cardiac ryanodine receptor (RYR2) gene has been
      detected in a number of unrelated families with various clinical phenotypes,
      including catecholaminergic polymorphic ventricular tachycardia (CPVT). This
      genomic deletion results in an in-frame deletion of exon-3 (Ex3-del). To
      understand the underlying disease mechanism of the RyR2 Ex3-del mutation, we
      generated a mouse model in which the RyR2 exon-3 sequence plus 15-bp intron
      sequences flanking exon-3 were deleted. Heterozygous Ex3-del mice (Ex3-del+/-)
      survived, but no homozygous Ex3-del mice were born. Unexpectedly, the Ex3-del+/-
      mice are not susceptible to CPVT. Ex3-del+/- cardiomyocytes exhibited similar
      amplitude but altered dynamics of depolarization-induced Ca2+ transients compared
      to wild type (WT) cells. Immunoblotting analysis revealed markedly reduced
      expression of RyR2 protein in the Ex3-del+/- mutant heart, indicating that Ex3
      del has a major impact on RyR2 protein expression in mice. Cardiac specific,
      conditional knockout of the WT RyR2 allele in Ex3-del+/- mice led to bradycardia
      and death. Thus, the absence of CPVT and other phenotypes in Ex3-del+/- mice may
      be attributable to the predominant expression of the WT RyR2 allele as a result
      of the markedly reduced expression of the Ex3-del mutant allele. The effect of
      Ex3-del on RyR2 protein expression is discussed in relation to the phenotypic
      variability in individuals with the RyR2 exon-3 deletion.

PMID- 24743770
TI  - First evaluation of drug-resistant Mycobacterium tuberculosis clinical isolates
      from Congo revealed misdetection of fluoroquinolone resistance by line probe
      assay due to a double substitution T80A-A90G in GyrA.
AB  - BACKGROUND: Tuberculosis (TB) is one of the major public health problems in
      Congo. However, data concerning Mycobacterium tuberculosis drug resistance are
      lacking because of the insufficient processing capacity. So, the aim of this
      study was to investigate for the first time the resistance patterns and the
      strain lineages of a sample of M. tuberculosis complex (MTBC) isolates collected
      in the two main cities of Congo. METHODS: Over a 9-day period, 114 smear-positive
      sputa isolated from 114 patients attending centers for the diagnosis and
      treatment of TB in Brazzaville and Pointe Noire were collected for culture and
      drug susceptibility testing (DST). Detection of mutations conferring drug
      resistance was performed by using line probe assays (GenoType MTBDRplus and
      MTBDRsl) and DNA sequencing. Strain lineages were determined by MIRU-VNTR
      genotyping. RESULTS: Of the 114 sputa, 46 were culture positive for MTBC. Twenty
      one (46%) were resistant to one or more first-line antiTB drugs. Of these, 15
      (71%) were multidrug resistant (MDR). The most prevalent mutations involved in
      rifampin and isoniazid resistance, D516V (60%) in rpoB and S315T (87%) in katG
      respectively, were well detected by MTBDRplus assay. All the 15 MDR strains were
      susceptible to fluoroquinolone and injectable second-line drug. No mutation was
      detected in the rrs locus involved in resistance to amikacin and capreomycin by
      both the MTBDRsl assay and DNA sequencing. By contrast, 9 MDR strains belonging
      to the same cluster related to T-family were identified as being falsely
      resistant to fluoroquinolone by the MTBDRsl assay due to the presence of a double
      substitution T80A-A90G in GyrA. CONCLUSIONS: Taken together, these data revealed
      a possible spread of a particular MDR clone in Congo, misidentified as
      fluoroquinolone resistant by MTBDRsl assay. Thus, this test cannot replace gold
      standard culture method and should be interpreted carefully in view of the
      patient's native land.

PMID- 24743771
TI  - Co-gradient variation in growth rate and development time of a broadly
      distributed butterfly.
AB  - Widespread species often show geographic variation in thermally-sensitive traits,
      providing insight into how species respond to shifts in temperature through time.
      Such patterns may arise from phenotypic plasticity, genetic adaptation, or their
      interaction. In some cases, the effects of genotype and temperature may act
      together to reduce, or to exacerbate, phenotypic variation in fitness-related
      traits across varying thermal environments. We find evidence for such
      interactions in life-history traits of Heteronympha merope, a butterfly
      distributed across a broad latitudinal gradient in south-eastern Australia. We
      show that body size in this butterfly is negatively related to developmental
      temperature in the laboratory, in accordance with the temperature-size rule, but
      not in the field, despite very strong temperature gradients. A common garden
      experiment on larval thermal responses, spanning the environmental extremes of H.
      merope's distribution, revealed that butterflies from low latitude (warmer
      climate) populations have relatively fast intrinsic growth and development rates
      compared to those from cooler climates. These synergistic effects of genotype and
      temperature across the landscape (co-gradient variation) are likely to accentuate
      phenotypic variation in these traits, and this interaction must be accounted for
      when predicting how H. merope will respond to temperature change through time.
      These results highlight the importance of understanding how variation in life
      history traits may arise in response to environmental change. Without this
      knowledge, we may fail to detect whether organisms are tracking environmental
      change, and if they are, whether it is by plasticity, adaptation or both. 

PMID- 24743772
TI  - Validation of endogenous normalizing genes for expression analyses in adult human
      testis and germ cell neoplasms.
AB  - The measurement of gene expression levels in cells and tissues typically depends
      on a suitable point of reference for inferring biological relevance. For
      quantitative (or real-time) RT-PCR assays, the method of choice is often to
      normalize gene expression data to an endogenous gene that is stably expressed
      across the samples analysed: a so-called normalizing or housekeeping gene.
      Although this is a valid strategy, the identification of stable normalizing genes
      has proved challenging and a gene showing stable expression across all cells or
      tissues is unlikely to exist. Therefore, it is necessary to define suitable
      normalizing genes for specific cells and tissues. Here, we report on the
      performance of a panel of nine commonly employed normalizing genes in adult human
      testis and testicular pathologies. Our analyses revealed significant variability
      in transcript abundance for commonly used normalizers, highlighting the
      importance of selecting appropriate normalizing genes as comparative measurements
      can yield variable results when different normalizing genes are employed. Based
      on our results, we recommend using RPS20, RPS29 or SRSF4 when analysing relative
      gene expression levels in human testis and associated testicular pathologies.
      OCT4 and SALL4 can be used with caution as second-tier normalizers when
      determining changes in gene expression in germ cells and germ cell tumour
      components, but the relative transcript abundance appears variable between
      different germ cell tumour types. We further recommend that such studies should
      be accompanied by additional assessment of histology and cellularity of each
      sample. 

PMID- 24743773
TI  - Computational prediction of alanine scanning and ligand binding energetics in G
      protein coupled receptors.
AB  - Site-directed mutagenesis combined with binding affinity measurements is widely
      used to probe the nature of ligand interactions with GPCRs. Such experiments, as
      well as structure-activity relationships for series of ligands, are usually
      interpreted with computationally derived models of ligand binding modes. However,
      systematic approaches for accurate calculations of the corresponding binding free
      energies are still lacking. Here, we report a computational strategy to
      quantitatively predict the effects of alanine scanning and ligand modifications
      based on molecular dynamics free energy simulations. A smooth stepwise scheme for
      free energy perturbation calculations is derived and applied to a series of
      thirteen alanine mutations of the human neuropeptide Y1 receptor and series of
      eight analogous antagonists. The robustness and accuracy of the method enables
      univocal interpretation of existing mutagenesis and binding data. We show how
      these calculations can be used to validate structural models and demonstrate
      their ability to discriminate against suboptimal ones. 

PMID- 24743774
TI  - Adult health outcomes of childhood bullying victimization: evidence from a five
      decade longitudinal British birth cohort.
AB  - OBJECTIVE: The authors examined midlife outcomes of childhood bullying
      victimization. METHOD: Data were from the British National Child Development
      Study, a 50-year prospective cohort of births in 1 week in 1958. The authors
      conducted ordinal logistic and linear regressions on data from 7,771 participants
      whose parents reported bullying exposure at ages 7 and 11 years, and who
      participated in follow-up assessments between ages 23 and 50 years. Outcomes
      included suicidality and diagnoses of depression, anxiety disorders, and alcohol
      dependence at age 45; psychological distress and general health at ages 23 and
      50; and cognitive functioning, socioeconomic status, social relationships, and
      well-being at age 50. RESULTS: Participants who were bullied in childhood had
      increased levels of psychological distress at ages 23 and 50. Victims of frequent
      bullying had higher rates of depression (odds ratio=1.95, 95% CI=1.27-2.99),
      anxiety disorders (odds ratio=1.65, 95% CI=1.25-2.18), and suicidality (odds
      ratio=2.21, 95% CI=1.47-3.31) than their nonvictimized peers. The effects were
      similar to those of being placed in public or substitute care and an index of
      multiple childhood adversities, and the effects remained significant after
      controlling for known correlates of bullying victimization. Childhood bullying
      victimization was associated with a lack of social relationships, economic
      hardship, and poor perceived quality of life at age 50. CONCLUSIONS: Children who
      are bullied-and especially those who are frequently bullied-continue to be at
      risk for a wide range of poor social, health, and economic outcomes nearly four
      decades after exposure. Interventions need to reduce bullying exposure in
      childhood and minimize long-term effects on victims' well-being; such
      interventions should cast light on causal processes.

PMID- 24743776
TI  - lgl Regulates the Hippo Pathway Independently of Fat/Dachs, Kibra/Expanded/Merlin
      and dRASSF/dSTRIPAK.
AB  - In both Drosophila and mammalian systems, the Hippo (Hpo) signalling pathway
      controls tissue growth by inhibiting cell proliferation and promoting apoptosis.
      The core pathway consists of a protein kinase Hpo (MST1/2 in mammals) that is
      regulated by a number of upstream inputs including Drosophila Ras Association
      Factor, dRASSF. We have previously shown in the developing Drosophila eye
      epithelium that loss of the apico-basal cell polarity regulator lethal-(2)-giant
      larvae (lgl), and the concomitant increase in aPKC activity, results in ectopic
      proliferation and suppression of developmental cell death by blocking Hpo pathway
      signalling. Here, we further explore how Lgl/aPKC interacts with the Hpo pathway.
      Deregulation of the Hpo pathway by Lgl depletion is associated with the
      mislocalization of Hpo and dRASSF. We demonstrate that Lgl/aPKC regulate the Hpo
      pathway independently of upstream inputs from Fat/Dachs and the
      Kibra/Expanded/Merlin complex. We show depletion of Lgl also results in
      accumulation and mislocalization of components of the dSTRIPAK complex, a major
      phosphatase complex that directly binds to dRASSF and represses Hpo activity.
      However, depleting dSTRIPAK components, or removal of dRASSF did not rescue the
      lgl-/- or aPKC overexpression phenotypes. Thus, Lgl/aPKC regulate Hpo activity by
      a novel mechanism, independently of dRASSF and dSTRIPAK. Surprisingly, removal of
      dRASSF in tissue with increased aPKC activity results in mild tissue overgrowth,
      indicating that in this context dRASSF acts as a tumor suppressor. This effect
      was independent of the Hpo and Ras Mitogen Activated Protein Kinase (MAPK)
      pathways, suggesting that dRASSF regulates a novel pathway to control tissue
      growth. 

PMID- 24743777
TI  - STAT3 Target Genes Relevant to Human Cancers.
AB  - Since its discovery, the STAT3 transcription factor has been extensively studied
      for its function as a transcriptional regulator and its role as a mediator of
      development, normal physiology, and pathology of many diseases, including
      cancers. These efforts have uncovered an array of genes that can be positively
      and negatively regulated by STAT3, alone and in cooperation with other
      transcription factors. Through regulating gene expression, STAT3 has been
      demonstrated to play a pivotal role in many cellular processes including
      oncogenesis, tumor growth and progression, and stemness. Interestingly, recent
      studies suggest that STAT3 may behave as a tumor suppressor by activating
      expression of genes known to inhibit tumorigenesis. Additional evidence suggested
      that STAT3 may elicit opposing effects depending on cellular context and tumor
      types. These mixed results signify the need for a deeper understanding of STAT3,
      including its upstream regulators, parallel transcription co-regulators, and
      downstream target genes. To help facilitate fulfilling this unmet need, this
      review will be primarily focused on STAT3 downstream target genes that have been
      validated to associate with tumorigenesis and/or malignant biology of human
      cancers. 

PMID- 24743781
TI  - Effects of antibiotics administration on the incidence of wound infection in
      percutaneous dilatational tracheostomy.
AB  - The effect of antibiotics during the perioperative period of percutaneous
      dilatational tracheostomy (PDT) is still controversial. A total of 297 patients
      who underwent the PDT procedure were divided into 2 groups:those administered
      antibiotics perioperatively and those not administered antibiotics. Wound
      infections were noted in 7 cases (incidence rate, 2.36%) and no death was
      recorded. Of the 69 patients without antibiotics, 5 developed wound infections
      (incidence rate, 7.25%), while only 2 of the 228 patients with antibiotics
      developed wound infections (incidence rate, 0.88%) (p=0.002;risk ratio, 8.82;95%
      confidence interval, 1.67-46.6). Of the 7 cases of wound infection, 5 cases
      occurred during the early period after PDT (within 7 days). Collectively, the
      present results suggest that prophylactic administration of antibiotics may
      prevent the incidence of PDT-induced wound infection, especially in the early
      phase after the PDT procedures. The need for antibiotics in PDT should be
      reconsidered.

PMID- 24743779
TI  - Loss of cilia causes embryonic lung hypoplasia, liver fibrosis, and cholestasis
      in the talpid3 ciliopathy mutant.
AB  - Sonic hedgehog plays an essential role in maintaining hepatoblasts in a
      proliferative non-differentiating state during embryogenesis. Transduction of the
      Hedgehog signaling pathway is dependent on the presence of functional primary
      cilia and hepatoblasts, therefore, must require primary cilia for normal
      function. In congenital syndromes in which cilia are absent or non-functional
      (ciliopathies) hepatorenal fibrocystic disease is common and primarily
      characterized by ductal plate malformations which underlie the formation of liver
      cysts, as well as less commonly, by hepatic fibrosis, although a role for
      abnormal Hedgehog signal transduction has not been implicated in these
      phenotypes. We have examined liver, lung and rib development in the talpid(3)
      chicken mutant, a ciliopathy model in which abnormal Hedgehog signaling is well
      characterized. We find that the talpid(3) phenotype closely models that of human
      short-rib polydactyly syndromes which are caused by the loss of cilia, and
      exhibit hypoplastic lungs and liver failure. Through an analysis of liver and
      lung development in the talpid(3) chicken, we propose that cilia in the liver are
      essential for the transduction of Hedgehog signaling during hepatic development.
      The talpid(3) chicken represents a useful resource in furthering our
      understanding of the pathology of ciliopathies beyond the treatment of thoracic
      insufficiency as well as generating insights into the role Hedgehog signaling in
      hepatic development.

PMID- 24743780
TI  - Analysis of molecular cytogenetic alteration in rhabdomyosarcoma by array
      comparative genomic hybridization.
AB  - Rhabdomyosarcoma (RMS) is the most common pediatric soft tissue sarcoma with poor
      prognosis. The genetic etiology of RMS remains largely unclear underlying its
      development and progression. To reveal novel genes more precisely and new
      therapeutic targets associated with RMS, we used high-resolution array
      comparative genomic hybridization (aCGH) to explore tumor-associated copy number
      variations (CNVs) and genes in RMS. We confirmed several important genes by
      quantitative real-time polymerase chain reaction (QRT-PCR). We then performed
      bioinformatics-based functional enrichment analysis for genes located in the
      genomic regions with CNVs. In addition, we identified miRNAs located in the
      corresponding amplification and deletion regions and performed miRNA functional
      enrichment analysis. aCGH analyses revealed that all RMS showed specific gains
      and losses. The amplification regions were 12q13.12, 12q13.3, and 12q13.3-q14.1.
      The deletion regions were 1p21.1, 2q14.1, 5q13.2, 9p12, and 9q12. The recurrent
      regions with gains were 12q13.3, 12q13.3-q14.1, 12q14.1, and 17q25.1. The
      recurrent regions with losses were 9p12-p11.2, 10q11.21-q11.22, 14q32.33,
      16p11.2, and 22q11.1. The mean mRNA level of GLI1 in RMS was 6.61-fold higher
      than that in controls (p = 0.0477) by QRT-PCR. Meanwhile, the mean mRNA level of
      GEFT in RMS samples was 3.92-fold higher than that in controls (p = 0.0354).
      Bioinformatic analysis showed that genes were enriched in functions such as
      immunoglobulin domain, induction of apoptosis, and defensin. Proto-oncogene
      functions were involved in alveolar RMS. miRNAs that located in the amplified
      regions in RMS tend to be enriched in oncogenic activity (miR-24 and miR-27a). In
      conclusion, this study identified a number of CNVs in RMS and functional analyses
      showed enrichment for genes and miRNAs located in these CNVs regions. These
      findings may potentially help the identification of novel biomarkers and/or drug
      targets implicated in diagnosis of and targeted therapy for RMS. 

PMID- 24743778
TI  - Transcription Factor STAT3 as a Novel Molecular Target for Cancer Prevention.
AB  - Signal Transducers and Activators of Transcription (STATs) are a family of
      transcription factors that regulate cell proliferation, differentiation,
      apoptosis, immune and inflammatory responses, and angiogenesis. Cumulative
      evidence has established that STAT3 has a critical role in the development of
      multiple cancer types. Because it is constitutively activated during disease
      progression and metastasis in a variety of cancers, STAT3 has promise as a drug
      target for cancer therapeutics. Recently, STAT3 was found to have an important
      role in maintaining cancer stem cells in vitro and in mouse tumor models,
      suggesting STAT3 is integrally involved in tumor initiation, progression and
      maintenance. STAT3 has been traditionally considered as nontargetable or
      undruggable, and the lag in developing effective STAT3 inhibitors contributes to
      the current lack of FDA-approved STAT3 inhibitors. Recent advances in cancer
      biology and drug discovery efforts have shed light on targeting STAT3 globally
      and/or specifically for cancer therapy. In this review, we summarize current
      literature and discuss the potential importance of STAT3 as a novel target for
      cancer prevention and of STAT3 inhibitors as effective chemopreventive agents. 

PMID- 24743782
TI  - Molecular simulation analysis of the structure complex of C2 domains of DKK
      family members and beta-propeller domains of LRP5/6: explaining why DKK3 does not
      bind to LRP5/6.
AB  - Dickkopf (DKK) proteins interact with low-density lipoprotein receptor-related
      protein 5/6 (LRP5/6) to modulate WNT signaling. The interaction is mediated by a
      cysteine-rich domain (C2) in the DKK protein and beta-propeller domains (PD) of
      LRP5/6. However, the third member of the DKK family (DKK3) does not bind to
      LRP5/6. To determine why DKK3 does not bind to the receptor domains, we performed
      a molecular modeling simulation study including homology modeling, protein
      protein docking and molecular dynamics (MD). The computed affinities
      (DeltaGbinding) between the C2 and PD models were consistent with the previously
      reported experimental results. The C2 model of DKK3 showed the lowest affinity
      for PD models. Multiple sequence alignment of C2 domains revealed that the DKK3
      genes have a unique 7-amino-acid insertion (L249-E255 in human DKK3) and P258 in
      a finger loop 1 (FL1). Interestingly, the insertion sequence is evolutionally
      conserved. MD simulations of high-affinity complex models of C2 and PD showed
      that FL1 directly interacts with the PD models and stabilizes the complex models.
      We also built a 7-amino-acid-deletion/P258G mutant model of DKK3C2 and estimated
      its affinities for the PD models. The affinity for human LRP5PD2 was increased by
      the substitution (DeltaGbinding=-48.9kcal/mol) and the affinity was compatible
      with that of high-affinity ligands. The results suggested that the lack of
      affinity between human DKK3 and human LRP5/6 results from: i) insertion of the 7
      amino acids, and ii) P258 in human DKK3. The sequence differences thus suggest an
      explanation for this unique property of DKK3.

PMID- 24743783
TI  - Prevalence of high-risk human papillomavirus (HR-HPV) infection among women with
      normal and abnormal cervical cytology in Myanmar.
AB  - This study aimed to determine the prevalence of normal and abnormal cervical
      cytology in women who attended the cervical cancer screening clinic of the
      Department of Medical Research in Lower Myanmar, and to determine the proportion
      of high-risk (HR) human papillomavirus (HPV) infection and HPV genotypes in women
      with normal and abnormal cervical cytology. A total of 1,771 women were screened
      from 2010 to 2011. Among them, 762 women (43.0%) had a normal smear, and
      866(48.9%) and 87 (4.9%) were diagnosed with inflammatory smears and atypical
      squamous cells of undetermined significance (ASCUS), respectively. Diagnoses of
      low-grade squamous intraepithelial lesion (LSIL) and high-grade squamous
      intraepithelial lesion (HSIL) numbered 42 (2.3%) and 11 (0.6%) respectively.
      Three cases of squamous cell carcinoma (SCC) (0.2%) were detected. Cervical swabs
      were collected from 96 women with abnormal cervical cytology and 20 with normal
      cytology. HR-HPV DNA testing was performed by polymerase chain reaction (PCR)
      with pU1M/pU2R primers. HR-HPV were identified in 35.5% (22/62) of inflammatory
      smears, 60% (6/10) of ASCUS, 86.7% (13/15) of LSIL, 50% (3/6) of HSIL, 100% (3/3)
      of SCC and 5% (1/20) of normal cytology. In PCR-positive cases, HPV genotyping
      was analyzed by the cleaved amplification polymorphism method. The most prevalent
      HPV genotypes were HPV-16 (60.4%) followed by HPV-31 (14.6%), HPV-18 (12.5%) and
      HPV-58 (12.5%). Women with abnormal cervical cytology were 10 times more likely
      to be HR-HPV positive than those with normal cytology (p=0.0001). This study
      suggests that the implementation of a cervical cytology screening program and
      routine vaccination against HPV in preadolescent and adolescent groups are needed
      to reduce the burden of HPV-associated cervical cancer.

PMID- 24743784
TI  - Molecular epidemiology and clinical implications of metallo-beta-lactamase
      producing Pseudomonas aeruginosa isolated from urine.
AB  - We conducted a study on molecular epidemiology and clinical implications of
      metallo-beta-lactamase (MBL)-producing Pseudomonas aeruginosa isolated from
      urine. Over a 10-year period from 2001 through 2010, a total of 92 MBL-producing
      P. aeruginosa urine isolates were collected from patients (one isolate per
      patient) who were admitted to 5 hospitals in Okayama Prefecture, Japan. When
      cross-infection was suspected in the hospital, pulsed-field gel electrophoresis
      was performed. In the resulting dendrogram of 79 MBL-producing P. aeruginosa
      urine isolates, no identical isolates and 7 pairs of isolates with >80%
      similarity were found. The biofilm-forming capabilities of 92 MBL-producing P.
      aeruginosa urine isolates were significantly greater than those of 92 non-MBL
      producing urine isolates in a medium of modified artificial urine. The imipenem
      resistance transferred in 16 of 18 isolates tested, and these frequencies were in
      the range of 10-3 to 10-9. All of 18 isolates tested belonged to internationally
      spread sequence type 235 and had 3 gene cassettes of antimicrobial resistance
      genes in the class 1 integron. The strong biofilm-forming capabilities of MBL
      producing P. aeruginosa urine isolates could be seriously implicated in
      nosocomial infections. To prevent spread of the organism and transferable genes,
      effective strategies to inhibit biofilm formation in medical settings are needed.

PMID- 24743785
TI  - Trends in geographic distribution of nursing staff in Japan from 2000 to 2010: a
      multilevel analysis.
AB  - The aim of this study was to examine trends in the geographic distribution of
      nursing staff in Japan from 2000 to 2010. We examined time trends in the rates of
      nursing staff per 100,000 population across 349 secondary health service areas.
      Using the Gini coefficient as a measure of inequality, we separately analyzed the
      data of 4 nursing staff types:public health nurses (PHN), midwives (MW), nurses
      (NS), and associate nurses (AN). Then, using multilevel Poisson regression
      models, we calculated the rate ratios (RRs) and their 95% confidence intervals
      (CIs) for each type of nursing staff per 1-year change. Overall, the distribution
      of PHN, MW, and NS improved slightly in terms of the Gini coefficient. After
      adjusting for prefectural capital and population density, PHN, MW, and NS
      significantly increased;the RRs per 1-year increment were 1.022 (95% CI:1.020
      1.023), 1.021 (95% CI:1.019-1.022), and 1.037 (95% CI:1.037-1.038), respectively.
      In contrast, AN significantly decreased;the RR per 1-year increment was 0.993
      (95% CI:0.993-0.994). Despite the considerable increase in the absolute number of
      nursing staff in Japan (excluding AN), this increase did not lead to a sufficient
      improvement in distribution over the last decade.

PMID- 24743786
TI  - Assistant-based standardization of prone position thoracoscopic esophagectomy.
AB  - Thoracoscopic esophagectomy in the prone position (TEPP) might enable solo
      surgery in cases requiring resection of the esophagus and the surrounding lymph
      nodes due to the associated advantages of good exposure of the surgical field and
      ergonomic considerations for the surgeon. However, no one approach can be for all
      patients requiring extensive lymphadenectomy. We recently developed an assistant
      based procedure to standardize exposure of the surgical field. Patients were
      divided into 1 of 2 groups:a pre-standardization group (n=37) and a post
      standardization group (n=28). The thoracoscopic operative time was significantly
      shorter (p=0.0037) in the post-standardization group (n=28; 267 +/- 31 min) than
      in the pre-standardization group (n=37;301 +/- 53 min). Further, learning curve
      analysis using the moving average method showed stabilization of the
      thoracoscopic operative time after the standardization. No significant
      differences were found in the number of mediastinal lymph nodes dissected or
      intraoperative blood loss between the 2 groups. There were also no significant
      differences in the complication rate. Assistant-based surgery and standardization
      of the procedure resulted in a well-exposed and safe surgical field. TEPP
      decreased the operative time, even in patients requiring extensive
      lymphadenectomy.

PMID- 24743787
TI  - Detection of RBM15-MKL1 fusion was useful for diagnosis and monitoring of minimal
      residual disease in infant acute megakaryoblastic leukemia.
AB  - Acute megakaryocytic leukemia (AMKL) with t(1;22)(p13;q13) is a distinct category
      of myeloid leukemia by WHO classification and mainly reported in infants and
      young children. Accurate diagnosis of this type of AMKL can be difficult, because
      a subset of patients have a bone marrow (BM) blast percentage of less than 20%
      due to BM fibrosis. Therefore, it is possible that past studies have
      underestimated this type of AMKL. We present here the case of a 4-month-old
      female AMKL patient who was diagnosed by presence of the RBM15-MKL1 (OTT-MAL)
      fusion transcript by RT-PCR. In addition, we monitored RBM15-MKL1 fusion at
      several time points as a marker of minimal residual disease (MRD), and found that
      it was continuously negative after the first induction chemotherapy even by
      nested RT-PCR. Detection of the RBM15-MKL1 fusion transcript thus seems to be
      useful for accurate diagnosis of AMKL with t(1;22)(p13;q13). We recommend that
      the RBM15-MKL1 fusion transcript be analyzed for all suspected AMKL in infants
      and young children. Furthermore, monitoring of MRD using this fusion transcript
      would be useful in treatment of AMKL with t(1;22)(p13;q13).

PMID- 24743788
TI  - Discordance between train-of-four response and clinical symptoms in a patient
      with amyotrophic lateral sclerosis.
AB  - A 47-year-old woman with amyotrophic lateral sclerosis was scheduled for total
      thyroidectomy with cervical node dissection. During anesthetic management by
      total intravenous anesthesia using remifentanil, propofol, and rocuronium, train
      of-four (TOF) monitoring findings were not consistent with clinical signs.
      Sugammadex successfully reversed shallow respiration. 

PMID- 24743789
TI  - A chemical approach to "rewire" neural progenitor cells.
AB  - Generation of neural progenitor cells (NPCs) from pluripotent stem cells
      including ESCs and iPSCs and derivation of NPCs from somatic tissues have been
      considered promising approaches that could be used therapeutically to restore
      function in patients suffering neurodegenerative diseases. A new study published
      in Cell Research shows, for the first time, the generation of NPCs from somatic
      cells by small molecule compounds under hypoxia without exogenous transcription
      factors. 

PMID- 24743790
TI  - Independent evolutionary origin of fem paralogous genes and complementary sex
      determination in hymenopteran insects.
AB  - The primary signal of sex determination in the honeybee, the complementary sex
      determiner (csd) gene, evolved from a gene duplication event from an ancestral
      copy of the fem gene. Recently, other paralogs of the fem gene have been
      identified in several ant and bumblebee genomes. This discovery and the close
      phylogenetic relationship of the paralogous gene sequences led to the hypothesis
      of a single ancestry of the csd genetic system of complementary sex determination
      in the Hymenopteran insects, in which the fem and csd gene copies evolved as a
      unit in concert with the mutual transfers of sequences (concerted evolution).
      Here, we show that the paralogous gene copies evolved repeatedly through
      independent gene duplication events in the honeybee, bumblebee, and ant lineage.
      We detected no sequence tracts that would indicate a DNA transfer between the fem
      and the fem1/csd genes between different ant and bee species. Instead, we found
      tracts of duplication events in other genomic locations, suggesting that gene
      duplication was a frequent event in the evolution of these genes. These and other
      evidences suggest that the fem1/csd gene originated repeatedly through gene
      duplications in the bumblebee, honeybee, and ant lineages in the last 100 million
      years. Signatures of concerted evolution were not detectable, implicating that
      the gene tree based on neutral synonymous sites represents the phylogenetic
      relationships and origins of the fem and fem1/csd genes. Our results further
      imply that the fem1 and csd gene in bumblebees, honeybees, and ants are not
      orthologs, because they originated independently from the fem gene. Hence, the
      widely shared and conserved complementary sex determination mechanism in
      Hymenopteran insects is controlled by different genes and molecular processes.
      These findings highlight the limits of comparative genomics and emphasize the
      requirement to study gene functions in different species and major hymenopteran
      lineages. 

PMID- 24743792
TI  - Homonymous hemianopia due to Erdheim-Chester disease.
AB  - Erdheim-Chester disease (ECD) is a rare non-Langerhans cell histiocytosis
      typically affecting multiple organ systems. We report 2 patients who presented
      with homonymous hemianopia and were ultimately diagnosed with biopsy-confirmed
      ECD. We review the spectrum of ECD and its treatment as well as histopathological
      and immunohistochemical differentiation from other histiocytic disorders.

PMID- 24743791
TI  - The apical complex provides a regulated gateway for secretion of invasion factors
      in Toxoplasma.
AB  - The apical complex is the definitive cell structure of phylum Apicomplexa, and is
      the focus of the events of host cell penetration and the establishment of
      intracellular parasitism. Despite the importance of this structure, its molecular
      composition is relatively poorly known and few studies have experimentally tested
      its functions. We have characterized a novel Toxoplasma gondii protein, RNG2,
      that is located at the apical polar ring--the common structural element of apical
      complexes. During cell division, RNG2 is first recruited to centrosomes
      immediately after their duplication, confirming that assembly of the new apical
      complex commences as one of the earliest events of cell replication. RNG2
      subsequently forms a ring, with the carboxy- and amino-termini anchored to the
      apical polar ring and mobile conoid, respectively, linking these two structures.
      Super-resolution microscopy resolves these two termini, and reveals that RNG2
      orientation flips during invasion when the conoid is extruded. Inducible
      knockdown of RNG2 strongly inhibits host cell invasion. Consistent with this,
      secretion of micronemes is prevented in the absence of RNG2. This block, however,
      can be fully or partially overcome by exogenous stimulation of calcium or cGMP
      signaling pathways, respectively, implicating the apical complex directly in
      these signaling events. RNG2 demonstrates for the first time a role for the
      apical complex in controlling secretion of invasion factors in this important
      group of parasites.

PMID- 24743793
TI  - Pediatric optic nerve sheath meningioma.

PMID- 24743794
TI  - Identification of logic relationships between genes and subtypes of non-small
      cell lung cancer.
AB  - Non-small cell lung cancer (NSCLC) has two major subtypes: adenocarcinoma (AC)
      and squamous cell carcinoma (SCC). The diagnosis and treatment of NSCLC are
      hindered by the limited knowledge about the pathogenesis mechanisms of subtypes
      of NSCLC. It is necessary to research the molecular mechanisms related with AC
      and SCC. In this work, we improved the logic analysis algorithm to mine the
      sufficient and necessary conditions for the presence states (presence or absence)
      of phenotypes. We applied our method to AC and SCC specimens, and identified
      [Formula: see text] lower and [Formula: see text] higher logic relationships
      between genes and two subtypes of NSCLC. The discovered relationships were
      independent of specimens selected, and their significance was validated by
      statistic test. Compared with the two earlier methods (the non-negative matrix
      factorization method and the relevance analysis method), the current method
      outperformed these methods in the recall rate and classification accuracy on
      NSCLC and normal specimens. We obtained [Formula: see text] biomarkers. Among
      [Formula: see text] biomarkers, [Formula: see text] genes have been used to
      distinguish AC from SCC in practice, and other six genes were newly discovered
      biomarkers for distinguishing subtypes. Furthermore, NKX2-1 has been considered
      as a molecular target for the targeted therapy of AC, and [Formula: see text]
      other genes may be novel molecular targets. By gene ontology analysis, we found
      that two biological processes ('epidermis development' and 'cell adhesion') were
      closely related with the tumorigenesis of subtypes of NSCLC. More generally, the
      current method could be extended to other complex diseases for distinguishing
      subtypes and detecting the molecular targets for targeted therapy. 

PMID- 24743795
TI  - SRA regulates adipogenesis by modulating p38/JNK phosphorylation and stimulating
      insulin receptor gene expression and downstream signaling.
AB  - The Steroid Receptor RNA Activator (SRA) enhances adipogenesis and increases both
      glucose uptake and phosphorylation of Akt and FOXO1 in response to insulin. To
      assess the mechanism, we differentiated ST2 mesenchymal precursor cells that did
      or did not overexpress SRA into adipocytes using combinations of
      methylisobutylxanthine, dexamethasone and insulin. These studies showed that SRA
      overexpression promotes full adipogenesis in part by stimulation of
      insulin/insulin-like growth factor-1 (IGF-1) signaling. SRA overexpression
      inhibited phosphorylation of p38 mitogen activated protein kinase (MAPK) and c
      Jun NH2-terminal kinase (JNK) in the early differentiation of ST2 cells.
      Conversely, knockdown of endogenous SRA in 3T3-L1 cells increased phosphorylation
      of JNK. Knockdown of SRA in mature 3T3-L1 adipocytes reduced insulin receptor
      (IR) mRNA and protein levels, which led to decreased autophosphorylation of
      IRbeta and decreased phosphorylation of insulin receptor substrate-1 (IRS-1) and
      Akt. This likely reflects a stimulatory role of SRA on IR transcription, as
      transfection studies showed that SRA increased expression of an IR promoter
      luciferase reporter construct.

PMID- 24743796
TI  - Structures of Trypanosoma brucei methionyl-tRNA synthetase with urea-based
      inhibitors provide guidance for drug design against sleeping sickness.
AB  - Methionyl-tRNA synthetase of Trypanosoma brucei (TbMetRS) is an important target
      in the development of new antitrypanosomal drugs. The enzyme is essential, highly
      flexible and displaying a large degree of changes in protein domains and binding
      pockets in the presence of substrate, product and inhibitors. Targeting this
      protein will benefit from a profound understanding of how its structure adapts to
      ligand binding. A series of urea-based inhibitors (UBIs) has been developed with
      IC50 values as low as 19 nM against the enzyme. The UBIs were shown to be orally
      available and permeable through the blood-brain barrier, and are therefore
      candidates for development of drugs for the treatment of late stage human African
      trypanosomiasis. Here, we expand the structural diversity of inhibitors from the
      previously reported collection and tested for their inhibitory effect on TbMetRS
      and on the growth of T. brucei cells. The binding modes and binding pockets of 14
      UBIs are revealed by determination of their crystal structures in complex with
      TbMetRS at resolutions between 2.2 A to 2.9 A. The structures show binding of the
      UBIs through conformational selection, including occupancy of the enlarged
      methionine pocket and the auxiliary pocket. General principles underlying the
      affinity of UBIs for TbMetRS are derived from these structures, in particular the
      optimum way to fill the two binding pockets. The conserved auxiliary pocket might
      play a role in binding tRNA. In addition, a crystal structure of a ternary
      TbMetRS*inhibitor*AMPPCP complex indicates that the UBIs are not competing with
      ATP for binding, instead are interacting with ATP through hydrogen bond. This
      suggests a possibility that a general 'ATP-engaging' binding mode can be utilized
      for the design and development of inhibitors targeting tRNA synthetases of other
      disease-causing pathogen. 

PMID- 24743797
TI  - Reference valence effects of affective s-R compatibility: are visual and auditory
      results consistent?
AB  - Humans may be faster to avoid negative words than to approach negative words, and
      faster to approach positive words than to avoid positive words. That is an
      example of affective stimulus-response (S-R) compatibility. The present study
      identified the reference valence effects of affective stimulus-response (S-R)
      compatibility when auditory stimulus materials are used. The researchers explored
      the reference valence effects of affective S-R compatibility using a mixed-design
      experiment based on visual words, visual pictures and audition. The study
      computed the average compatibility effect size. A t-test based on visual pictures
      showed that the compatibility effect size was significantly different from zero,
      t (22) = 2.43, p<.05 (M = 485 ms). Smaller compatibility effects existed when
      switching the presentation mode from visual stimuli to auditory stimuli. This
      study serves as an important reference for the auditory reference valence effects
      of affective S-R compatibility. 

PMID- 24743799
TI  - Salt-bridge energetics in halophilic proteins.
AB  - Halophilic proteins have greater abundance of acidic over basic and very low
      bulky hydrophobic residues. Classical electrostatic stabilization was suggested
      as the key determinant for halophilic adaptation of protein. However,
      contribution of specific electrostatic interactions (i.e. salt-bridges) to
      overall stability of halophilic proteins is yet to be understood. To understand
      this, we use Adaptive-Poison-Boltzmann-Solver Methods along with our home-built
      automation to workout net as well as associated component energy terms such as
      desolvation energy, bridge energy and background energy for 275 salt-bridges from
      20 extremely halophilic proteins. We then perform extensive statistical analysis
      on general and energetic attributes on these salt-bridges. On average, 8 salt
      bridges per 150 residues protein were observed which is almost twice than earlier
      report. Overall contributions of salt-bridges are -3.0 kcal mol-1. Majority (78%)
      of salt-bridges in our dataset are stable and conserved in nature. Although,
      average contributions of component energy terms are equal, their individual
      details vary greatly from one another indicating their sensitivity to local micro
      environment. Notably, 35% of salt-bridges in our database are buried and stable.
      Greater desolvation penalty of these buried salt-bridges are counteracted by
      stable network salt-bridges apart from favorable equal contributions of bridge
      and background terms. Recruitment of extensive network salt-bridges (46%) with a
      net contribution of -5.0 kcal mol-1 per salt-bridge, seems to be a halophilic
      design wherein favorable average contribution of background term (-10 kcal mol-1)
      exceeds than that of bridge term (-7 kcal mol-1). Interiors of proteins from
      halophiles are seen to possess relatively higher abundance of charge and polar
      side chains than that of mesophiles which seems to be satisfied by cooperative
      network salt-bridges. Overall, our theoretical analyses provide insight into
      halophilic signature in its specific electrostatic interactions which we hope
      would help in protein engineering and bioinformatics studies. 

PMID- 24743800
TI  - Comparative analysis of P450 signature motifs EXXR and CXG in the large and
      diverse kingdom of fungi: identification of evolutionarily conserved amino acid
      patterns characteristic of P450 family.
AB  - Cytochrome P450 monooxygenases (P450s) are heme-thiolate proteins distributed
      across the biological kingdoms. P450s are catalytically versatile and play key
      roles in organisms primary and secondary metabolism. Identification of P450s
      across the biological kingdoms depends largely on the identification of two P450
      signature motifs, EXXR and CXG, in the protein sequence. Once a putative protein
      has been identified as P450, it will be assigned to a family and subfamily based
      on the criteria that P450s within a family share more than 40% homology and
      members of subfamilies share more than 55% homology. However, to date, no
      evidence has been presented that can distinguish members of a P450 family. Here,
      for the first time we report the identification of EXXR- and CXG-motifs-based
      amino acid patterns that are characteristic of the P450 family. Analysis of P450
      signature motifs in the under-explored fungal P450s from four different phyla,
      ascomycota, basidiomycota, zygomycota and chytridiomycota, indicated that the
      EXXR motif is highly variable and the CXG motif is somewhat variable. The amino
      acids threonine and leucine are preferred as second and third amino acids in the
      EXXR motif and proline and glycine are preferred as second and third amino acids
      in the CXG motif in fungal P450s. Analysis of 67 P450 families from biological
      kingdoms such as plants, animals, bacteria and fungi showed conservation of a set
      of amino acid patterns characteristic of a particular P450 family in EXXR and CXG
      motifs. This suggests that during the divergence of P450 families from a common
      ancestor these amino acids patterns evolve and are retained in each P450 family
      as a signature of that family. The role of amino acid patterns characteristic of
      a P450 family in the structural and/or functional aspects of members of the P450
      family is a topic for future research. 

PMID- 24743801
TI  - Altered hypothalamic functional connectivity with autonomic circuits and the
      locus coeruleus in migraine.
AB  - The hypothalamus has been implicated in migraine based on the manifestation of
      autonomic symptoms with the disease, as well as neuroimaging evidence of
      hypothalamic activation during attacks. Our objective was to determine functional
      connectivity (FC) changes between the hypothalamus and the rest of the brain in
      migraine patients vs. control subjects. This study uses fMRI (functional magnetic
      resonance imaging) to acquire resting state scans in 12 interictal migraine
      patients and 12 healthy matched controls. Hypothalamic connectivity seeds were
      anatomically defined based on high-resolution structural scans, and FC was
      assessed in the resting state scans. Migraine patients had increased hypothalamic
      FC with a number of brain regions involved in regulation of autonomic functions,
      including the locus coeruleus, caudate, parahippocampal gyrus, cerebellum, and
      the temporal pole. Stronger functional connections between the hypothalamus and
      brain areas that regulate sympathetic and parasympathetic functions may explain
      some of the hypothalamic-mediated autonomic symptoms that accompany or precede
      migraine attacks. 

PMID- 24743803
TI  - [Establishment of drug resistant cell line of MGC-803 and analysis of
      differential secretome].
AB  - OBJECTIVE: To identify chemoresistance-associated secretory proteins by proteomic
      approaches, and to provide the basis for selecting suitable chemotherapy in
      gastric cancer treatment. METHODS: Drug resistant cell lines were established by
      gradient drug treatment with MGC-803 gastric cancer cells. The secreted proteins
      of MGC-803 parental and resistant cells were collected from the conditional
      medium without serum and separated by two-dimensional gel electrophoresis (2
      DE).The proteins were analyzed by PD Quest 7.1.0 software and identified by
      matrix-assisted laser desorption ionization time-of-flight mass spectrometry
      (MALDI-TOF-MS). Real-time RT-PCR was performed to confirm the difference of
      expression on the mRNA level. RESULTS: The 5-fluorouracil (5FU), paclitaxel (TA)
      and cisplatin (DDP)-resistant gastric cancer cell lines with the resistance
      indexes of 110.6, 70.0 and 13.3 respectively, were established successfully. DDP
      resistant cells had strong cross-resistance to 5FU and TA, and the resistance
      indexes were 23.5 and 114.0. 5FU-resistant cells also had strong cross-resistance
      to TA with the resistance index 70.0. The 2-DE patterns of protein component
      spectra from the conditional medium were obtained with 18 proteins whose
      abundances were increased in all chemoresistance cells for more than 2-fold, 13
      of which were identified by mass spectrometry, including protease and proteins
      involved in signal transduction. Compared with the parental cell MGC-803, SLMAP,
      TOP3A, DYNC1H1, RHPN1, PUF60 and SIAH1 were significantly up-regulated in three
      drug resistant cells, IFT172 and FILIP were up-regulated in 5FU-resistant and TA
      resistant cells, PLVAP and LMNA were up-regulated in TA- and DDP-resistant cells.
      Further validation revealed that SIAH1 protein was enriched in cell lysates and
      the conditional medium from all the drug resistant cells. CONCLUSION: By
      establishing the 5FU-,TA- and DDP-resistant gastric cancer cell lines and
      assisted by 2-DE and mass spectrometry, we demonstrated the different secretory
      protein profiling and found that SIAH1 had significantly increased in both cell
      lysates and the conditional medium of the drug-resistant cells, which are
      potential candidates for developing chemoresistance markers in sera from gastric
      cancer patients.

PMID- 24743802
TI  - A randomized, double-blind evaluation of D-cycloserine or alprazolam combined
      with virtual reality exposure therapy for posttraumatic stress disorder in Iraq
      and Afghanistan War veterans.
AB  - OBJECTIVE: The authors examined the effectiveness of virtual reality exposure
      augmented with D-cycloserine or alprazolam, compared with placebo, in reducing
      posttraumatic stress disorder (PTSD) due to military trauma. METHOD: After an
      introductory session, five sessions of virtual reality exposure were augmented
      with D-cycloserine (50 mg) or alprazolam (0.25 mg) in a double-blind, placebo
      controlled randomized clinical trial for 156 Iraq and Afghanistan war veterans
      with PTSD. RESULTS: PTSD symptoms significantly improved from pre- to
      posttreatment across all conditions and were maintained at 3, 6, and 12 months.
      There were no overall differences in symptoms between D-cycloserine and placebo
      at any time. Alprazolam and placebo differed significantly on the Clinician
      Administered PTSD Scale score at posttreatment and PTSD diagnosis at 3 months
      posttreatment; the alprazolam group showed a higher rate of PTSD (82.8%) than the
      placebo group (47.8%). Between-session extinction learning was a treatment
      specific enhancer of outcome for the D-cycloserine group only. At posttreatment,
      the D-cycloserine group had the lowest cortisol reactivity and smallest startle
      response during virtual reality scenes. CONCLUSIONS: A six-session virtual
      reality treatment was associated with reduction in PTSD diagnoses and symptoms in
      Iraq and Afghanistan veterans, although there was no control condition for the
      virtual reality exposure. There was no advantage of D-cycloserine for PTSD
      symptoms in primary analyses. In secondary analyses, alprazolam impaired recovery
      and D-cycloserine enhanced virtual reality outcome in patients who demonstrated
      within-session learning. D-cycloserine augmentation reduced cortisol and startle
      reactivity more than did alprazolam or placebo, findings that are consistent with
      those in the animal literature.

PMID- 24743804
TI  - [Cloning of the Helicobacter pylori thioredoxin-1 gene and characterization].
AB  - OBJECTIVE: To clone the Helicobacter pylori (Hp) thioredoxin-1 (Trx1) gene and
      construct the recombinant expression vector containing the target gene, then to
      express and purify the protein, and detect its activity. METHODS: The cDNA gene
      of the Hp Trx1 was amplified by RT-PCR from the international standard strain
      26695, using the specific primers containing double endonuclease digesting sites.
      The Hp Trx1 cDNA was then inserted into the pEASY-T1 vector to construct the
      pEASY-T1-Hp Trx1 recombinant vector. The next step was to double digest the pEASY
      T1-Hp Trx1 recombinant vector and insert the target gene into pET-30a to
      construct the pET-30a-Hp Trx1 recombinant vector, which was transferred to E.coli
      BL21 plys S to express the Hp Trx1 protein. The recombinant protein was purified
      by Ni affinity chromatography, and then its activity of disulfide reductase was
      detected. RESULTS: By DNA sequencing, the Hp Trx1 cDNA was successfully inserted
      into the pET-30a vector and was in accordance with GenBank (HP0824). The E.coli
      containing pET-30a-Hp Trx1 recombinant vector successfully expressed Hp Trx1
      protein. Through the detection of the activity, the recombinant Hp Trx1 protein
      was identified to have the activity of disulfide reductase. CONCLUSION: The
      prokaryotic expression vector pET-30a-Hp Trx1 was successfully constructed. The
      recombinant protein Hp Trx1 was successfully expressed and purified, which had
      the activity of disulfide reductase. This study lays the foundation for further
      research on the biological activity of Hp Trx1 and the mechanism of its function
      in tumor genesis.

PMID- 24743805
TI  - [Retrospective analysis for clinical and histopathological characteristics of
      basal cell carcinoma in 418 patients].
AB  - OBJECTIVE: To investigate the clinical and histopathological characteristics of
      basal cell carcinoma (BCC) in Chinese patients. METHODS: Clinical and
      pathological data of BCC confirmed by histology from 2010 to 2012 in Peking
      University First Hospital were retrospectively analyzed. RESULTS: Among 418
      patients enrolled, the male/female ratio was 0.77:1. The average age was (65.39+/
      13.51) years. Among the patients younger than 60 years who occupied 29% of all
      the cases, the male/female ratio was 1.16:1. In terms of the histology subtypes
      of the BCCs, 81.8% were nodular, followed by superficial (9.8%), and the others
      were in very small proportion. The head and face were the most common sites of
      BCC (86.6%). All morpheaform subtypes, and the majority of the nodular subtypes
      were located on the head and face, whereas the trunk and extremities were the
      most common locations for the others. Clinically, 86.6% of the BCC were pigmented
      and 80.4% were not ulcerated. The diagnostic accordance rates of BCC on the head
      and face (84.7%) and on the trunk (79.1%) were higher than those on the
      extremities (46.2%, P<0.05). CONCLUSION: The most clinical and histopathological
      characteristics of our cases were similar to those of Caucasian. This study
      displays some unique characteristics. The young and middle aged patients occupied
      relative higher proportion, and their gender ration was different from that of
      the aged group. Tumor with hyperpigmentation was popular and few cases were
      ulcerated. In this study, multiple BCC cases were seldom, and the BCC patients
      with nevus sebaceous were older than those in other reports. The research of the
      diagnostic accordance rates of BCC revealed that both doctors and patients should
      pay more attention to BCC.

PMID- 24743806
TI  - Significance of serum peptidylarginine deiminase type 4 in ANCA-associated
      vasculitis.
AB  - OBJECTIVE: To investigate the clinical significance of peptidylarginine deiminase
      type 4 (PAD4) in the pathogenesis of antineutrophil cytoplasmic antibody (ANCA)
      associated vasculitis (AAV). To make a primary observation on the relationship of
      chronic bronchitis and bronchiectasis (CB) with the pathogenesis of AAV by PAD4.
      METHODS: The sera from 13 patients with AAV, 13 patients with CB, 11 patients
      with rheumatoid arthritis (RA), 11 patients with primary chronic kidney disease
      (CKD) and 12 normal controls were collected. Serum PAD4 was detected using
      commercial ELISA kits. The serum levels of PAD4 were compared not only among the
      different groups but also between the activity and remission stage of the same
      disease. The associations between serum PAD4 and the Birmingham Vasculitis
      Activity Score (BVAS) of AAV were further investigated. RESULTS: (1) The serum
      levels of PAD4 in patients with AAV, RA and CB at activity stage were all higher
      than that in the normal controls (P<0.001, respectively, alpha'=0.007). The serum
      level of PAD4 in patients with CB at remission stage and that in CKD group were
      not found elevated compared with the normal controls (P=0.02, P=0.085,
      respectively, alpha'=0.007). (2) At activity stage, among the groups of simple
      AAV, AAV with a long history of CB and CB without AAV, no significant difference
      was detected. While at remission stage among the 3 groups, the serum level of
      PAD4 was at the lowest level in CB group without AAV. (3) The serum level of PAD4
      in some patients with CB without AAV were found still higher at remission stage.
      (4) The serum level of PAD4 in AAV with renal damage at activity stage was
      positively correlated with BVAS (the activity score of AAV, r=0.71, P=0.02).
      CONCLUSION: PAD4 is involved in the pathogenesis of AAV. Whether some patients
      with CB might progress to AAV by the link with PAD4 still need further
      investigation.

PMID- 24743807
TI  - [Left atrial size predicts adverse cardiac events in patients with non
      obstruction hypertrophic cardiomyopathy].
AB  - OBJECTIVE: To evaluate the relationship between left atrial size and the risk of
      cardiac events in patients with non-obstruction hypertrophic cardiomyopathy.
      METHODS: In the study, 39 patients who met inclusion criteria were followed up
      for (28.0+/-7.7) months. The patients were divided into two groups with or
      without major adverse cardiac events (a composite of arrhythmia, angina, syncope
      and congestive heart failure). Clinical and echocardiographic data of the two
      groups were compared. The predictive value of left atrial diameter (LAD) and left
      atrial volume index (LAVI) were reviewed by using receive operating
      characteristic curve (ROC). The events analysis was performed by using the Kaplan
      Meier analysis. RESULTS: Cardiac events occurred in 11 patients (28.2%). LAD, LAD
      index (LADI), LAV and LAVI were significantly greater in the patients with
      cardiac events than those without cardiac events [LAD: (4.28+/-0.63) cm vs.
      (3.85+/-0.48) cm, P=0.025; LADI: (0.048 9+/-0.011 1) cm/m(2) vs. (0.040 8+/-0.005
      8) cm/m(2), P=0.005; LAV: (60.8+/-16.2) mL vs. (46.2+/-14.0) mL, P=0.008; LAVI:
      (66.5+/-23.8) mL/m(2) vs. (49.6+/-15.9) mL/m(2), P=0.014]. An LAD of >4.29 cm
      identified patients with cardiac events with a sensitivity of 63.6% and a
      specificity of 89.3%. An LAVI of >53.1 mL/m(2) identified patients with cardiac
      events with a sensitivity of 72.7% and a specificity of 71.4%. The Kaplan-Meier
      analysis indicated that the patients with LAD>4.29 cm or LAVI>53.1 mL/m(2) had
      higher incidence of cardiac events. CONCLUSION: LAD and LAVI may be effective
      markers for predicting adverse cardiac events in patients with non-obstruction
      hypertrophic cardiomyopathy.

PMID- 24743808
TI  - [Effect of Y chromosomal length variation on male reproductive dysfunction].
AB  - OBJECTIVE: To investigate the effects of big and bit Y chromosome configurations
      on male fertility and to evaluate the relevant clinical significance. METHODS:
      The relevant cases were divided into A and B groups. Group A included male
      infertile cases. Group B included cases whose wives had adverse pregnancy history
      or the abnormal amniotic fluid punctures. The cytogenetics of the patients were
      examined by culturing peripheral-blood lymphocytes and G-banding technology, and
      karyotyping analysis techniques were used to study the big and bit Y chromosomes
      in the two different groups. RESULTS: Among 2 139 cases, 98 cases were found with
      abnormal karyotype of big and bit Y chromosomes. There was no significant
      difference in the abnormal rate of the length variation of the Y chromosomal
      karyotypes between the male infertility group and the adverse pregnancy outcome
      group. In the male infertile group (group A), there was no significant difference
      in the abnormal rate between the big Y chromosome and the bit Y chromosome. In
      the group with adverse pregnancy outcomes (group B), the abnormal rate of the big
      Y chromosome karyotyping was significantly higher than that of the bit Y
      chromosome karyotyping. The main clinical effects of groups A and B were
      azoospermia, oligozoospermia, poor spermia, abortion, embryonic diapause and
      fetal anomalies, etc . CONCLUSION: The big and bit Y chromosomal abnormality
      results in not only the male infertility directly, but also an important and
      continuous reason of adverse pregnancy outcomes, of which the detailed mechanism
      needs to be further investigated.

PMID- 24743809
TI  - [Retrospective analysis of the clinical characteristics and visual outcomes of
      postoperative endophthalmitis of cataract between 2001 and 2012].
AB  - OBJECTIVE: To analyze the incidence, clinical characteristics and visual outcomes
      of postoperative endophthalmitis of cataract. METHODS: Reviewed all the 15
      electronic surgical records of cataract surgery during the last 12 years in
      Peking University First Hospital and summarized the incidence, onset time,
      symptoms, clinical signs and pathogenic characteristics of endophthalmitis.
      Analyzed the laws of vision changes and the related factors of visual outcomes.
      The data were analyzed with SPSS 14.0. RESULTS: The overall rate of
      endophthalmitis was 0.17%, while most of the patients had serious symptoms and
      low vision. The onset time of the disease was 23.8 days on average, while that of
      the acute cases was 6 days. The positive rate of bacterial examination was 60%
      and all of the results were G+ (77% was Staphylococcus epidermidis). The visual
      acuity after treatment was improved to varying degrees. Our research had revealed
      that the factors related to the visual outcome included post-surgery visual
      acuity (r=0.746,P<0.01), presenting visual acuity at the onset of endophthalmitis
      (r=0.667,P<0.01), posterior capsular rupture occurrence (P<0.05) and ocular
      irritation symptoms (P<0.05). CONCLUSION: Better visual outcome of
      endophthalmitis after cataract surgery is correlated with positive and correct
      treatment. The vision and signs of the patients are useful to predict the visual
      outcomes.

PMID- 24743810
TI  - [Analysis on urban elderly people's preference for prevention and treatment of
      non-communicable diseases].
AB  - OBJECTIVE: To investigate the outpatient provider preference and its influencing
      factors among residents older than 45 years in China's urban areas. METHODS: The
      data of China Health and Retirement Longitudinal Survey (CHARLS) taking place in
      the year 2011 were analyzed with the method of multinominal logistic regression.
      RESULTS: In the last month, the rates of respondents with hypertension or/and
      diabetes who were reported being ill and seeking treatment were higher than that
      of those without such diseases. 51.73% of the hypertensive and 64.81% of the
      diabetic preferred hospitals to community health service (CHS) and private
      clinics. Regression results showed that people with Urban Employee Basic Medical
      Insurance (UEBMI), higher education level, higher capacity to pay and diabetes
      tended to choose hospitals rather than CHS. CONCLUSION: Urban people with non
      communicable diseases (NCDs) preferred to use hospitals rather than the CHS,
      which reflected CHS's low performance in NCDs management. UEBMI failed to channel
      off the insured people to CHS. CHS needs to strengthen its ability to manage
      NCDs, and UEBMI should implement measures to attract patients' flow to CHS.

PMID- 24743811
TI  - [Analysis on the disease burden and its impact factors of coal worker's
      pneumoconiosis inpatients].
AB  - OBJECTIVE: To obtain the baseline data and decision of quantitative analysis for
      the allocation of scarce health care resources,and for the health policymaking
      about easing the disease burden, to provide estimation of the economic costs and
      the disability-adjusted life years (DALYs) loss of the coal worker's
      pneumoconiosis (CWP) and to explore the influencing factors of the disease
      burden. METHODS: The CWP inpatients from the Institute of Occupational Diseases
      Prevention and Control of a Coal Mining Group for 2011 were recruited in the
      study. Multiple dimensions of the disease burden were measured in the inception
      cohort of the 194 CWP inpatients: the direct economic burden, the indirect
      economic burden and the DALYs loss. The direct economic burden of the inpatients
      included hospitalization expenses and food allowances and nutritional
      supplements. The indirect economic burden was estimated using the DALYs and human
      capital approach,and the influencing factors of hospitalization expenses were
      analyzed in this study. RESULTS: The estimated direct economic burden for the 194
      CWP inpatients for 2011 was approximately 4.68 million yuan and direct burden per
      capita was 24 108.05 yuan, and their indirect burden about 6.98 million yuan and
      indirect burden per capita 35 977.36 yuan. The study discovered that 1 681.53
      health years were lost for the CWP inpaitents and per capita health years loss
      (8.67+/-3.65) years. CONCLUSION: The medical cost, the indirect cost and the
      DALYs loss of CWP are all sizable. Age and length of stay in the hospital are the
      major influencing factors for high hospitalization expenses. The hospitalization
      expenses of the CWP inpatients increase with their age and length of stay in the
      hospital. Taking effective measures to reduce the morbility is the key point to
      reduce the CWP burden.

PMID- 24743812
TI  - [Effects of lead exposure on 18 elements in blood and excretions in rats].
AB  - OBJECTIVE: To investigate the effects of lead exposure on lead and other metal
      elements contents in rats. METHODS: SD rats were randomly divided into control
      group and several experiment groups of different doses. The rats were exposed to
      lead acetate through intragastric administration every other day for 5 times. The
      whole blood, urine and feces of all the rats were collected. The concentrations
      of lead and 18 metal elements in these samples were determined by inductively
      coupled plasma mass spectrometry (ICP-MS) and inductively coupled plasma atom
      emission spectrometry (ICP-AES). RESULTS: No significant difference among the
      groups was found for body weight and organ-body ratios of the rats after lead
      exposure (P>0.05). With the increase of exposure dose, lead content in blood,
      total lead in urine and feces tended to increase, while the total lead in urine
      no longer increased in the high dose group. Significant differences among the
      groups (P<0.05) were observed for the sodium, magnesium, potassium, strontium,
      antimony, thallium and bismuth contents in the whole blood, the potassium, iron
      and antimony contents in the urine, and the calcium, iron, zinc, copper,
      thallium, bismuth and rare earth elements contents in the feces. CONCLUSION: The
      effect of lead on the metabolism of divalent metal ions, namely calcium,
      magnesium, iron, zinc, copper and strontium ion, may be due to the competition of
      lead with the ions for common delivery carrier. Lead exposure induces the
      excretion of light rare earth elements and toxic elements (thallium and bismuth),
      and changes the antimony, sodium and potassium contents in rats. But there is no
      effect of lead on molybdenum and cadmium in rats.

PMID- 24743813
TI  - [Comparison of daily intake of lutein+zeaxanthin, serum concentration of
      lutein/zeaxanthin and lipids profile between age-related macular degeneration
      patients and controls].
AB  - OBJECTIVE: To compare the daily intake of lutein+zeaxanthin, serum concentrations
      of lutein, zeaxanthin and serum lipids between age-related macular degeneration
      (AMD) patients and controls. METHODS: AMD was diagnosed and graded according to
      the fundus morphology and the standard of age-related eye disease study (AREDS).
      In the study, 51 subjects with early AMD, 51 with medium AMD and 51 without AMD
      as controls were recruited. Food frequency questionnaires were used to calculate
      the daily intake of lutein and zeaxanthin. The concentrations of serum lutein and
      zeaxanthin were measured by HPLC and the concentrations of serum lipids including
      serum total cholesterol (TC), triglyceride (TG), high density lipoprotein (HDL)
      and low density lipoprotein (LDL) were measured by Roche full-automatic
      biochemical analyzer. RESULTS: The daily intake of lutein+zeaxanthin, the
      concentrations of serum lutein and serum zeaxanthin of the subjects with medium
      AMD were 7 870.458 MUg/d, 0.180 MUmol/L, 0.029 MUmol/L respectively, which were
      all significantly lower than those of the controls (11 297.959 MUg/d, 0.285
      MUmol/L, 0.044 MUmol/L, P<0.05); The concentrations of serum HDL of the subjects
      with early and medium AMD were (1.29+/-0.27) mmol/L and (1.16+/-0.30) mmol/L
      respectively, both of which were significantly lower than that of the controls
      [(1.45+/-0.35) mmol/L, P<0.001]. CONCLUSION: The development of AMD might be
      affected by the daily intake of lutein+zeaxanthin and the serum concentrations of
      lutein and zeaxanthin. The concentration of serum HDL might be related to the
      occurrence of AMD.

PMID- 24743814
TI  - [Analysis of the determinants of salt-restriction behavior among urban and rural
      residents in Beijing with health belief model].
AB  - OBJECTIVE: To investigate salt-restriction behavior and explore related
      determinants among Beijing residents, so as to provide scientific basis for salt
      restriction intervention. METHODS: The health belief model (HBM) was applied in
      designing the questionnaire, in which respondents' demographic characteristics,
      salt-restriction behavior, knowledge on hypertension, perceived susceptibility to
      hypertension, perceived severity of hypertension, perceived benefits of salt
      restriction, perceived subjective barriers of salt-restriction, perceived
      objective barriers of salt-restriction, self-efficacy and cues to action were
      measured. Altogether 799 residentsresponsible for cooking in Xicheng district
      (396 urban residents) and Shunyi district (403 rural residents) in Beijing were
      investigated by the questionnaire, salt intake follow up, and 24-hour urinary
      sodium (24HUNa) determination. RESULTS: In the study, 54.0% (214/396) of urban
      respondents and 26.3% (106/403) of rural respondents used a salt-restriction
      spoon with high frequencies (everyday and often), while 27.5% (109/396) and 12.4%
      (50/403) used it correctly. The daily salt intake was (5.85+/-4.17) g and (7.74+/
      4.67) g, and the 24HUNa was (113.70+/- 72.57) mmoL and (212.18+/-105.01) mmoL for
      urban and rural respondents, respectively. Perceived objective barriers of salt
      restriction was animportant determinant of salt-restriction behavior for both the
      rural (OR=0.92; 95%CI: 0.88-0.96; P<0.01) and urban respondents (OR=0.87;95%CI:
      0.83-0.91;P<0.01), which was perceived obviously more by rural respondents than
      by urban ones. Another important determinant of rural respondents' salt
      restriction behavior was the owning status of salt-restriction-spoon
      (OR=2.18;95%CI: 1.04-4.57;P=0.04). CONCLUSION: It is necessary to improve current
      salt-restriction-spoon, enhance its owning rate,and popularize its correct way of
      using, especially among rural residents.

PMID- 24743815
TI  - [Descriptive epidemiological study on disabilities attributed to non-dementia
      organic mental disorder in China].
AB  - OBJECTIVE: To describe the prevalence rates of disabilities attributed to non
      dementia organic mental disorder and their demographic and regional distributions
      in China for supporting policy maker to prevent mental disabilities. METHODS:
      Using the data from the second China National Survey on Disability, the
      prevalence rates were statistically analysed. RESULTS: There were 1 200 people
      with non-dementia organic mental disabilities in 2 526 145 respondents, the point
      prevalence rate of disabilities attributed to non-dementia organic mental
      disorder was 0.4750/00, ranking the third in all mental disabilities. Among the
      disabled, more male and more people with lower education level, being unemployed,
      divorced, widowed and unmarried were found. The decline of disability prevalence
      rates in different ethnic groups was found in the sequence of Uighur, Tibetan,
      Hui-Chinese (Muslims), Han-Chinese and Mongolian. The disability prevalence rates
      in Uighur and Tibetan were double higher than those in Han-Chinese and Hui
      Chinese with statistical significances. The disability prevalence rates increased
      with age. Regarding the region distribution of non-dementia organic mental
      disabilities, the prevalence rate in western region was higher than that in
      eastern region. Among the eight economic regions, the prevalence rates in the
      underdeveloped southwest, south, northwest regions were significantly higher than
      those in the others. The proportions of extremely severe, severe, moderate, and
      mild disability were 36.8%, 17.0%, 14.3%, and 31.9%. The severest impairment on
      function of daily activities was found in the disabled. CONCLUSION: The
      proportion of non-dementia organic mental disabilities is relative high in all
      mental disabilities, therefore it should be focused for prevention and treatment.
      The disabled in males, with lower economic and education level, worse marital
      status, and being unemployed should receive more attention.

PMID- 24743816
TI  - [Multi-center retrospective analysis of clinical and related sociologic
      characteristics of postoperative distal radius fracture patients].
AB  - OBJECTIVE: To study clinical-related characteristics of sociology of
      postoperative distal radius fracture patients. METHODS: A multi-center
      retrospective research was conducted on the information of the case evaluation
      and follow-up, including the patients' gender, age, habits, history of chronic
      diseases, conditions of fracture, length of hospital stay and treatments. The
      epidemiology data were analyzed with SPSS15.0. RESULTS: Of the entire 143
      patients, 52 were male (average age: 41), and 91 were female (average age: 61).
      The different gender and age groups had significant distinction in the
      characteristics of injury. The length of hospital stay was influenced by the
      energy of injury. CONCLUSION: To reduce the damage or incidence of distal radius
      fracture, we should avoid falling, strengthen protection awareness, treat
      internal medicine diseases or osteoporosis and so on. The knowledge of
      characteristics of sociology and injury of distal radius fracture is beneficial
      to the prevention and treatment.

PMID- 24743817
TI  - [Analysis of the HapMap data on SNPs in SUMO1 and association study of rs7599810
      in trios with non-syndromic cleft lip with or without cleft palate].
AB  - OBJECTIVE: To analyze the minor allele frequencies (MAFs), haplotype block and
      haplotype frequencies for single nucleotide polymorphisms (SNPs) in SUMO1 using
      HapMap data and perform association analysis between SNPs in SUMO1 and non
      syndromic cleft lip with or without cleft palate (NSCL/P) using 183 trios
      recruited from Shandong Province. METHODS: SNPs with MAF>0.01 and Hardy-Weinberg
      equilibrium (P>0.01) were identified as qualified SNPs by Haploview. The MAFs of
      qualified SNPs were analyzed and the relative range ratios of the MAFs were
      developed to measure the differences in MAFs for common qualified SNPs with
      mutual minor allele among the samples. Haplotype blocks and haplotype frequencies
      for common qualified SNPs in four samples were analyzed and compared among the
      samples. Transmission disequilibrium test (TDT) was carried out to identify the
      association between rs7599810 and NSCL/P using 183 NSCL/P case-parent trios.
      RESULTS: Among the 24 SNPs released by HapMap project, the number of monotonic
      SNPs was 9 in Han Chinese in Beijing, China (CHB) and Japanese in Tokyo, Japan
      (JPT) samples, 8 in Utah residents with Northern and Western European ancestry
      from the CEPH collection (CEU) sample, and 6 in Yoruban in Ibadan, Nigeria (YRI)
      sample. The 12 common qualified SNPs in the four samples formed one haplotype in
      each sample. There were 3, 3, 5, and 6 forms of haplotypes in the CHB, JPT, CEU,
      and YRI samples respectively, and the cumulative frequencies for the 2 most
      common haplotypes ranged from 0.634 to 0.922. Significant transmission
      disequilibrium of G allele at rs7599810 from parents to offspring was not shown
      (chi(2)=0.485, P=0.486, OR=0.898, 95% CI: 0.663-1.021) for rs7599810 in Shandong
      Han sample. CONCLUSION: SNPs in SUMO1 mainly showed common features in minor
      alleles, MAFs and haplotype blocks among CHB, JPT and CEU samples, but unique
      features in YRI compared with those for the other three samples. Although no
      association was established between the markers in SUMO1 and NSCL/P using data
      from Shandong Han population, our analysis suggests further studies are
      warranted.

PMID- 24743818
TI  - [Association between chronic periodontitis and metabolic syndrome related
      mitochondria single nucleotide polymorphism].
AB  - OBJECTIVE: To investigate the relationship between Mitochondrial DNA(mtDNA) SNP
      and the severity of periodontitis. METHODS: In the study, 227 subjects in a
      community of Beijing received questionnaire interview, periodontal examination
      and biochemical laboratory examination in 2005. The designed primer was used to
      amplify the specific mtDNA fragments with PCR, and sequence the PCR products.
      Finally, the relationship between severity of chronic periodontitis and mtDNA SNP
      at site 10398 was analyzed. RESULTS: The number of the subjects included at mtDNA
      site 10398 was 227. The G allele frequency in the metabolic syndrome(MS) subjects
      was significantly higher than that in the non MS subjects [80(70.2%) vs.
      34(29.8%),P=0.039 ]. The result of Logistic regression showed that the subjects
      with G allele had higher risk of MS than the subjects with A
      allele(OR=1.77,95%CI=1.02-3.06, P=0.042). But there was no significant
      relationship between the 10398 A->G SNP and severity of periodontitis.
      CONCLUSION: In this population, mtDNA SNP 10398 A->G may be associated with MS.
      However, there was no relationship between the 10398 A->G SNP and severity of
      chronic periodontitis.

PMID- 24743819
TI  - [Association between AXIN2 polymorphism and oligodontia].
AB  - OBJECTIVE: To explore the association between AXIN2 polymorphism and oligodontia
      in Chinese population. METHODS: We employed 97 individuals diagnosed with
      sporadic non-syndromic oligodontia and 200 healthy control subjects. Their DNA
      was obtained from the whole blood or buccul swap samples and the genotyping was
      performed by polymerase chain reaction (PCR). RESULTS: Significant differences
      were observed in the allele and genotype frequencies of rs145353986 of AXIN2.
      Distributions of genotypes GG, GC and CC of rs145353986 polymorphism were
      significantly different between the case group and the control group (P = 0.011)
      and C allelic frequency was higher in the case group (P=0.002). CONCLUSION: These
      data demonstrate an association between rs145353986 of AXIN2 and non-syndromic
      oligodondia in the Chinese population. Furthermore, AXIN2 can be regarded as a
      marker gene for the risk of tooth agenesis.

PMID- 24743820
TI  - [Isolation, culture and ultrastructure analysis of mesenchymal stem cells from
      human periodontal ligament].
AB  - OBJECTIVE: To isolate and culture human periodontal ligament stem cells (PDLSCs)
      and observe its ultrastructure. METHODS: The proliferation and growth
      characteristics of human periodontal ligament cells were observed in primary
      culture and colony culture. PDLSCs were isolated by magnetic activated cell
      sorting (MACS) and ultrastructural characterization was observed by electron
      microscopy. RESULTS: When the cells were cultured at low density, PDLSCs grew in
      a colony-like manner. With the exception of a small amount of rough endoplasmic
      reticulum, ribosomes, and mitochondria, relatively few organelles were found in
      the cytoplasm, suggesting that they had remained undifferentiated. CONCLUSION:
      PDLSCs showed colony-like growth capacity and had ultrastructural
      characterization with stem cells. This indicated that PDLSCs could act as the
      appropriate seed cells for cell-based periodontal tissue regeneration.

PMID- 24743821
TI  - [Intracellular mechanisms of Porphyromonas gingivalis induced interleukin-8
      upregulation in endothelial cells].
AB  - OBJECTIVE: To find out the mechanisms by which Porphyromonas gingivalis (P.
      gingivalis) regulates interleukin (IL)-8 expression in endothelial cells.
      METHODS: P. gingivalis was applied to infect human umbilical vein endothelial
      cells (HUVECs), and the expressions of nucleotide binding oligomerization domain
      (NOD) 1, NOD2 and IL-8 were detected at mRNA and protein levels. Then the
      NOD1/NOD2 gene was silenced by RNA interference targeting NOD1 or NOD2 mRNA,
      followed by P. gingivalis treatment in the HUVECs, and the expression levels of
      NOD1/NOD2 and IL-8 were examined by real-time PCR, Western-blot or ELISA. In
      order to confirm the relationship between NOD1/NOD2 and IL-8 in the HUVECs, the
      agonists for NOD1 and NOD2, DAP and MDP were used in this study. RESULTS: P.
      gingivalis was activated the expressions of NOD1 and NOD2 in the HUVECs.
      Meanwhile, IL-8 expression level was also upreguated after P. gingivalis
      treatment (P<0.01). Knocking down of NOD1 or NOD2, the expression level of NOD1
      or NOD2 was decreased, and P. gingivalis-induced IL-8 expression was attenuated
      in the HUVECs (P<0.01). Compared with normal cells, the NOD1 and NOD2 agonists,
      DAP and MDP, successfully increased IL-8 expression respectively (P<0.05).
      CONCLUSION: NOD1 and NOD2 play an important role in the inflammation of HUVECs
      caused by P. gingivalis in the expression of IL-8.

PMID- 24743822
TI  - [Influence of thermalcycling on bonding durability of self-etch adhesives with
      dentin].
AB  - OBJECTIVE: To investigate influence of thermalcycling on the bonding durability
      of two one-step products [Adper Prompt (AP) and G-bond (GB)] and one two-step
      self-etching adhesive [Clearfil SE bond (SE)] with dentin in vitro. METHODS:
      Forty-two extracted human molars were selected. The superficial dentin was
      exposed by grinding off the enamel. The teeth were randomly distributed into six
      groups with varied bonding protocols. The adhesives were applied to the dentin
      surface. Composite crowns were built up, then the samples were cut longitudinally
      into sticks with 1.0 mm*1.0 mm bonding area [for microtensile bond strength
      (MTBS) testing] or 1.0 mm thick slabs (for nanoleakage observation). Bonding
      performance was evaluated with or without thermalcyling. For the MTBS testing,
      the strength values were statistically analysed using One-Way ANOVA. Four slabs
      in each group were observed for nanoleakage by SEM with a backscattered electron
      detector. RESULTS: Thermalcycling procedures affected MTBS. In the two one-step
      groups, the MTBS decreased significantly (P<0.05) after thermalcycling [AP group
      from (19.06+/-1.50) MPa to (12.62+/-2.10) MPa; GB group from (17.75+/-1.10) MPa
      to (6.24+/-0.42)MPa]. But in SE groups, MTBS did not significantly affect
      [(45.80+/-2.97) MPa compared with(40.60+/-5.76) MPa]. As a whole, one-step self
      etching adhesives showed lower MTBS than two-step bonding system after aging.For
      AP and GB, continuous nanoleakage appearance was notable and more obvious than
      for SE. CONCLUSION: Thermalcycling can affect the bonding performance of self
      etch adhesives including decrease of bond strength and nanoleakage pattern. one
      step self-etch adhesives showed more obvious change compared with their two-step
      counterparts.

PMID- 24743823
TI  - [Volume measurements of human parotid and submandibular glands].
AB  - OBJECTIVE: To accurately measure the volume of normal human parotid and
      submandibular glands, establish the normal values of the volumes of the glands,
      and apply the technique in the diagnosis of swollen salivary glands of the
      patients with IgG4-related sialadenitis. METHODS: Two hundred and forty cases
      with normal parotid and submandibular glands who received CT examination were
      divided into 4 groups according to the age standards raised by the Society of
      Geriatrics Chinese Medical Association and WHO (2000) age standards . 3D CT
      images of parotid and submandibular glands were reconstructed by technique of
      volume rendering. Volumes of normal parotid and submandibular glands were
      measured and their normal values were analyzed. The volumes of swollen parotid
      and submandibular glands from 30 cases with IgG4-related sialadenitis were
      compared with the normal values. RESULTS: 3D images of parotid and submandibular
      glands were well established by volume rendering. The normal values(95%confidence
      interval, 95%CI) of CT volume of parotid gland were as follows: adolescent group
      of males: 16.993-20.975 cm(3), females: 13.908-16.696 cm(3); young group of
      males: 20.015-24.359 cm(3), females: 18.089-21.135 cm(3); middle-aged group of
      males: 28.638-35.122 cm(3), females: 19.588-22.474 cm(3); young elderly and
      elderly group of males: 28.792-35.082 cm(3), females: 28.783-34.909 cm(3). The
      normal values (95%CI) of submandibular gland were as follows: adolescent group of
      males: 7.202-8.852 cm(3), females: 6.494-8.126 cm(3); young group of males: 7.759
      9.523 cm(3), females: 7.285-8.605 cm(3); middle-aged group of males: 8.423-10.177
      cm(3), females: 7.905-9.309 cm(3); young elderly and elderly group of males:
      8.310-10.510 cm(3), females: 7.003-8.203 cm(3). The volumes of parotid glands
      increased with age. but no significant change was found in those of submandibular
      glands. The volumes of the swollen glands from the patients with IgG4-related
      sialadenitis were significantly larger than those of the normal glands.
      CONCLUSION: Volumes of the parotid and submandibular glands could be definitely
      and quantitively measured by CT volume rendering. The established normal values
      in this study could be taken as the reference for the diagnosis of parotid and
      submandibular gland enlargement .

PMID- 24743824
TI  - [Computer-assisted implant restoration of free-end partially edentulous mandible
      with severe vertical bone deficiency].
AB  - OBJECTIVE: To evaluate the applicability, accuracy and clinical outcome of the
      computer assisted design and computer assisted manufacture (CAD & CAM) tooth
      supported implant surgical guide in the mandibular free-end partially edentulous
      patients with insufficient vertical bone height. METHODS: According to the
      inclusion criteria, 3 patients (2 women, and 1 man) with the mean age of 45 years
      (from 44 to 46 years) with 10 implant sites were involved in this study. With the
      help of Computer-assisted-design software to plan and simulate the surgical
      strategies, the implant surgical guides were fabricated via the rapid prototyping
      technique, then the guided implant placement was implemented, finally the post
      surgical evaluations were accomplished by the clinical and radiographic
      examinations. RESULTS: Ten implants were placed in 3 mandibles via the surgical
      guides, and the implant supported non-split restorations were in place. All the
      implant restorations revealed good clinical function until the last review. No
      inferior alveolar nerve injury was detected by the clinical neurosensory test.
      The immediate post surgical CBCT was performed to confirm a safe distance of 1.5
      to 3.0 mm between the implant apical and the nerve canal. The deviations between
      the planed and the actually placed implant were: coronal deviation (0.84+/-0.30)
      mm (0.31-1.24 mm); apical deviation (1.42+/-0.52) mm (0.52-2.36 mm); angular
      deviation 7.65 degrees +/-1.84 degrees  (4.43 degrees -9.81 degrees ).
      CONCLUSION: In case of distal free-end partially edentulous with insufficient
      vertical bone height in the posterior mandibular region, computer assisted
      surgical design and guided surgery can offer a treatment option with minimal
      invasiveness and a shorter treatment period, and avoid the complicated bone
      augmentation procedure and the high risk of nerve transposition. This technique
      is clinically and technically feasible, but the cases using this technique should
      be strictly selected according to the indication.

PMID- 24743825
TI  - [Effects of wearing dentures on sleep breathing among edentulous people: a
      preliminary study].
AB  - OBJECTIVE: To investigate the effects of wearing dentures on sleep breathing
      among edentulous people. METHODS: Nine edentulous people were recruited to
      participate in this selfcontrolled case series clinical study. Polysomnogram
      (PSG) was carried out on two consecutive nights, on one night the patients slept
      wearing dentures, and on the other without dentures. The indexes such as apnea
      and hypopnea index (AHI), L-SpO2, and morning blood pressure etc. were compared.
      RESULTS: Among the nine edentulous people, eight showed a higher AHI when they
      slept with dentures, and only one showed a lower AHI. The average AHI of the nine
      edentulous people was 8.82 without dentures and 11.72 with dentures, which meant
      that AHI was significantly higher when the edentulous people slept with dentures
      in their mouths (P<0.05). While no significant differences were found in the
      score of L-SpO2 and morning blood pressures (P>0.05). CONCLUSION: Wearing
      dentures might lead to an increase of AHI during sleep among edentulous people.

PMID- 24743826
TI  - [Effect of surface hot-etching treatment on zirconia/resin bonding strength].
AB  - OBJECTIVE: To evaluate the effect of hot-etching pretreatment of surface of
      zirconia on the shear bond strength of interface between zirconia and the two
      different resin cements. METHODS: Smooth enamel surfaces of fresh extracted human
      teeth and zirconia discs were prepared, and the surface of zirconia discs were
      treated with the following different methods: no treatment, airborne particle
      abrasion with 50 MUm Al2O3 particles, hot-etching treatment for 60 min. The
      surface morphology was observed with scanning electron microscope (SEM). Two
      commercial resin bond systems (Super Bond C&B and Panavia F2.0) were used to
      cement the zirconia discs to enamel surfaces according to the instruction. Shear
      bond test was conducted with universal testing machine at a crosshead speed of 1
      mm/min. Single-factor ANOVA (analysis of variance) statistical analysis was
      performed to compare the differences of shear bond strengths between the groups
      (alpha=0.01). RESULTS: The shear bond strengths of Super Bond group were (23.37+/
      3.94) MPa, (25.95+/-3.05) MPa and (34.52+/-1.8) MPa respectively for no
      treatment, airborne particle abrasion, and hot-etching treatments. The shear bond
      strengths of Panavia group were (12.91+/-3.33) MPa, (14.00+/-3.28) MPa, and
      (18.47+/-4.16) MPa respectively for no treatment, airborne particle abrasion, and
      hot-etching treatments. The shear bond strengths were increased by hot-etching
      treatment compared with no treatment and airborne particle abrasion treatment
      (P<0.01). CONCLUSION: The result indicated that the hot-etching technique could
      improve the shear bond strength between zirconia and resin cements.

PMID- 24743827
TI  - [Validation of the American College of Rheumatology classification criteria for
      primary Sjogren's syndrome in Chinese patients].
AB  - OBJECTIVE: To validate the American College of Rheumatology Classification (ACR)
      Criteria (2012) for the diagnosis of primary Sjogren's syndrome in Chinese
      patients. METHODS: All patients involved in this study came from the Department
      of Oral Medicine Peking University Stomatology Hospital. They were devided into
      two groups of pSS and non-pSS according to the diagnoses made by two experts.
      Both groups of the patients had completed medical records kept in the hospital.
      RESULTS: A total of 239 pSS patients (160 with labial salivary gland biopsy, and
      79 without biopsy) and 52 age-matched non-pSS patients [(55.17+/-14.295),and
      (55.90+/-13.38) years old, P>0.05] (9 with biopsy, and 43 without biopsy) were
      involved in this study. The sensitivity and specificity of ACR criteria in
      diagnosing pSS were 90.37 % and 88.46 % respectively. The positive and negative
      likelihood ratios were 7.83 and 0.109, respectively. The sensitivities of ACR
      criteria in diagnosing pSS patients with and without labial biopsy were 88.75%
      and 93.67 %, respectively, with specificities of 88.89% and 88.37%, respectively.
      The most sensitive item adopted in ACR criteria was the ocular staining score
      with a sensitivity of 85.77%, and the most specific item was the labial salivary
      gland biopsy, with a specificity of 88.89%. CONCLUSION: The sensitivity and
      specificity of ACR criteria in diagnosing Chinese pSS patients were relatively
      high, and may serve as the diagnosis criteria in research and clinical practice.
      However, the ACR criteria need to be validated and further revised in the future
      .

PMID- 24743828
TI  - [Comparison of phenotypic features between patients with X-linked and autosomal
      recessive Alport syndrome].
AB  - OBJECTIVE: To further improve the recognition of Alport syndrome. METHODS: The
      patients with COL4A3, COL4A4 or COL4A5 mutations, admitted to Department of
      Pediatric, Peking University First Hospital from 2005 to 2009, were
      retrospectively studied. Their clinical and ultrastructural characteristics were
      compared between the male patients with X-linked dominant inheritance Alport
      syndrome (XLAS) and the patients with autosomal recessive inheritance Alport
      syndrome (ARAS). RESULTS: There were 54 male patients with XLAS and 14 patients
      with ARAS. Compared with the male patients with XLAS, episodic gross hematuria
      was prominent (P<0.001) in patients with ARAS. Family history was also different
      between the two groups (P=0.016). However, there was no significant difference in
      the age of identification of symptoms, initial manifestations, levels of
      proteinuria, extrarenal signs and ultra-structural glomerular basement membrane
      changes between the two groups. CONCLUSION: There are some features that
      distinguish between the patients with XLAS and the patients with ARAS.

PMID- 24743829
TI  - [Long-term outcome and related factors of epileptic seizures in children].
AB  - OBJECTIVE: To analyze the Long-term outcome of seizures, and to explore the
      effects of related factors, including the age at onset, types of epileptic
      syndromes, and etiological factors, etc. METHODS: The clinical data were
      retrospectively surveyed from 265 children with regular follow-ups for over 1
      year at Peking University First Hospital (Jan. 2003 to Dec. 2006). The seizure
      free rate was calculated as an at least one-year non-occurrence of seizures. The
      Long-term outcome of seizures was analyzed in association with factors including
      the age at onset, types of epileptic syndromes, and etiology. RESULTS: (1)
      Seizure types were clarified in all the cases, with combined types of seizures in
      17. Epileptic syndromes were identified in 163/265 cases (61.5%). With regular
      antiepileptic drug therapy, 57.9% children with epilepsy could be seizure-free.
      (2) Seizure-free was demonstrated in 142/265 cases with a seizure-free rate of
      53.6% in this group. (3) The age at onset was youngest in the non-efficacy group.
      (4) The seizure-free rate was different by syndrome types of epilepsies, with a
      higher seizure-free rate in idiopathic generalized epilepsy (72.4%) and benign
      epilepsy in children with centro-temporal spikes (65.5%), whereas a lowest rate
      (21.7%) in infantile spasms. (5) A significant difference of seizure-free rates
      was revealed in different etiological groups. Children with idiopathic epilepsy
      achieved higher seizure-free rate (69.2%) than those with symptomatic and
      cryptogenic epilepsy (45.4%). CONCLUSION: The epilepsy children with regular
      antiepileptic drug therapy had generally satisfactory outcome of seizures, with
      over half cases of seizure-free. The prognosis was demonstrated to be closely
      related with the etiological factors, syndrome types and age at onset.

PMID- 24743830
TI  - [Prenatal ultrasonic manifestation and clinical significance of fetal
      hemivertebra].
AB  - OBJECTIVE: To explore the manifestation and clinical significance of prenatal
      ultrasound diagnosis of fetal hemivertebra. METHODS: In the study, 27 fetals with
      hemivertebras (proven by post-natal X-ray, CT or MR) were examined by prenatal
      ultrasound and MR in Women & Children's Hospital, Ningbo, Zhejiang. Two
      dimensional and three-dimensional prenatal ultrasonic manifestations were
      retrospective analyzed and compared with the prenatal MR diagnoses, the post
      natal X-ray, CT, MR examinations. All the fetuses were carried out karyotype
      examinations. The full-term births recieved surgical treatment and the Cobb angle
      correction rate was calculated. RESULTS: The 27 cases of fetal ultrasound showed
      the morphological changes of the spine, with the involved segment only half of
      the vertebra, in which 9 cases were single hemivertebra and 18 cases multiple, 8
      cases were no malformation and 19 cases other malformations, and 19 cases were
      induction of labor, and 8 cases of term delivery. Compared with postpartum X-ray
      and other imaging tests, the prenatal ultrasound accuracy rate was 92.5%, and
      prenatal MR 96.3%. In the 27 cases, the chromosome cultures of 25 cases were
      successful, in which the normal karyotype was 68.0% (17/25), and abnormal
      karyotype 32.0% (8/25) with multiple hemivertebra accounting for 47.1% (8/17). In
      8 cases with posterior approach of hemivertebra resection, 6 patients were less
      than and equal to 3 years old, whose average Cobb angle correction rate was
      38.02%, and 2 more than 3 years old, whose average Cobb angle correction rate was
      24.98%. CONCLUSION: Fetal hemivertebra have typical sonographic manifestations.
      In diagnosis of fetal hemivertebra, the accuracy of prenatal ultrasound is close
      to that of MR, which has important clinical implications in diagnosis and overall
      assessment of fetal hemivertebra, and can also provide appropriate clinical
      genetic reference.

PMID- 24743831
TI  - [Pregnancy outcome in 54 patients with antiphospholipid syndrome: a retrospective
      clinical study].
AB  - OBJECTIVE: To summarize the maternal/fetal outcome of pregnancy in
      antiphospholipid syndrome (APS) patients to evaluate the influence of treatment
      on the outcomes of pregnancy, and to investigate the possible clinical predictors
      of unsuccessful pregnancy. METHODS: The clinical characteristics, laboratory
      profiles and the outcomes of delivery of 54 APS patients from January 2000 to
      March 2013 were investigated retrospectively. RESULTS: (1) Maternal/fetal
      outcome: 17 pregnancies (31.4%) resulted in full term delivery, 7 (12.9%) in
      stillbirth, 16 (29.6%) in spontaneous abortion,10 (18.5%) in premature birth due
      to eclampsia or severe preeclampsia or signs of placental insufficiency, 4
      (7.4%)received therapeutic termination of pregnancy due to eclampsia or severe
      preeclampsia. In 27 live birth cases, 8 (29.6%) were fetal growth restriction, 4
      (14.8%) were low birth weight infants, and 3 (11.1%) were very low birth weight
      infants. (2) Influence of treatment on the pregnancy outcomes and complications:
      24 APS patients were given the treatment of aspirin or aspirin combined with low
      molecular weight heparin, and 30 patients received no treatment. Compared with
      the untreated group, the treated group had lower rate of fetal loss, higher rate
      of full-term delivery, increased gestational age and birth weight, decreased
      incidence of preeclampsia / eclampsia and thrombocytopenia. There was a
      significant difference between the two groups (P<0.05). (3)Possible risk factors
      of unsuccessful pregnancy: there were 17 successful pregnancies and 37
      unsuccessful pregnancy. The rate of double APL positive and antibody titers >=
      three times the upper limit of normal were higher in the unsuccessful pregnancy
      group than the successful pregnancy group. Antibody negative rate before
      pregnancy proportion of patients received treatment and the level of complement 4
      were lower in the unsuccessful pregnancy group. CONCLUSION: Pregnant women with
      APS are an extremely high risk group for adverse maternal /fetal outcome.
      Treatments can improve the pregnancy outcome of the APS patients. APL not turning
      negative before pregnancy double APL positive, antibody titers >= three times the
      upper limit of normal and complement 4 decrease may be the risk factors for
      pregnancy failure and treatment may be a protective factor for successful
      pregnancy.

PMID- 24743832
TI  - [Anesthesia and perioperative management for cesarean section in patient with
      factor XI deficiency: a case report].
AB  - Factor XI deficiency is a hereditary blood coagulation disorders. Puerpera with
      factor XI deficiency is exceedingly rare. A case of a 28-year-old woman who was
      found to have factor XI deficiency coagulopathy at the end of 33 weeks of
      gestation was presented here, and was admitted to Peking University Third
      Hospital at the end of 38 weeks of gestation. The doctors from several
      departments conducted cooperative management, and prepared with supplement of the
      coagulant factor and fresh frozen plasma before operation. The woman had general
      anesthesia, the baby was delivered successfully and the mother's condition was
      kept stable. The amount of bleeding of puerpera was not much perioperation. Yet
      the management of cesarean section with factor XI deficiency at home and abroad
      is still lack of standard guideline by now. 

PMID- 24743833
TI  - [Thoracic extramedullary subdural and epidural of inflammatory myofibroblastoma:
      a case report].
AB  - We present here a rare case of thoracic extramedullary subdural and epidural of
      leisions. The initial diagnosis of preoperation was hypertrophy of ligamentum
      flavum, however, after excision of the epidural lesions, the symptoms got worse.
      A second operation found the subdural leisions which were then totally resected.
      Two pathological examinations confirmed it was inflammatory myofibroblastic tumor
      (IMT). The incidence of this disease is extremely low. IMT is benign in
      histology, but it can be aggressive. The exact pathogenesis is still unknown.
      Tumor resection is the first choice to treat. Long-term follow-up with MRI is
      required for the patient. 

PMID- 24743834
TI  - Urethral diverticular stones first misdiagnosed as bladder stones on simple X
      ray.

PMID- 24743835
TI  - OSA is common and independently associated with hypertension and increased
      arterial stiffness in consecutive perimenopausal women.
AB  - BACKGROUND: Perimenopause is associated with increased cardiovascular risk. OSA
      is an emerging risk factor for cardiovascular disease, particularly among men,
      but the independent contribution of OSA to cardiovascular risk in climacteric
      women is not clear. METHODS: We evaluated 277 consecutive women (age, 56 [52-61]
      years; BMI, 28 [25-32] kg/m2) without manifest cardiovascular disease (heart
      failure, coronary disease, or stroke). All women underwent 24-h ambulatory BP
      monitoring, arterial stiffness evaluation (pulse wave velocity), and portable
      sleep study. RESULTS: OSA (apnea-hypopnea index >= 5 events/h) and moderate to
      severe OSA (apnea-hypopnea index >= 15 events/h) were diagnosed in 111 (40.1%)
      and 31 (11.1%) women, respectively. None of the participants had received a
      previous diagnosis of OSA. Women with moderate to severe OSA vs those without OSA
      had a higher prevalence of hypertension, were prescribed more medications for
      hypertension, had higher awake BP (systolic, 133 [125-142] vs 126 [119-134] mm Hg
      [P < .01]; diastolic, 82 [78-88] vs 79 [74-85] mm Hg [P = .07]), higher nocturnal
      BP (systolic, 125 [118-135] vs 115 [109-124] mm Hg [P < .01]; diastolic, 73 [69
      79] vs 69 [62-75] mm Hg [P < .01]), and more arterial stiffness (pulse wave
      velocity, 11.5 [10.1-12.3] m/s vs 9.5 [8.6-10.8] m/s, P < .001). Oxygen
      desaturation index during the night was independently associated with 24-h
      arterial BP and arterial stiffness (per five-unit increase in oxygen desaturation
      index, beta = 1.30 [95% CI, 0.02-2.54; P = .04] vs 0.22 [95% CI, 0.03-0.40; P =
      .02] in women with vs without OSA, respectively). CONCLUSIONS: OSA is common,
      underdiagnosed, and independently associated with high BP and increased arterial
      stiffness in perimenopausal women.

PMID- 24743836
TI  - Kind discrimination and competitive exclusion mediated by contact-dependent
      growth inhibition systems shape biofilm community structure.
AB  - Contact-Dependent Growth Inhibition (CDI) is a phenomenon in which bacteria use
      the toxic C-terminus of a large exoprotein (called BcpA in Burkholderia species)
      to inhibit the growth of neighboring bacteria upon cell-cell contact. CDI systems
      are present in a wide range of Gram-negative proteobacteria and a hallmark
      feature is polymorphism amongst the exoprotein C-termini (BcpA-CT in
      Burkholderia) and amongst the small immunity proteins (BcpI) that protect against
      CDI in an allele-specific manner. In addition to CDI, the BcpAIOB proteins of
      Burkholderia thailandensis mediate biofilm formation, and they do so independent
      of BcpA-mediated interbacterial competition, suggesting a cooperative role for
      CDI system proteins in this process. CDI has previously only been demonstrated
      between CDI+ and CDI- bacteria, leaving the roles of CDI system-mediated
      interbacterial competition and of CDI system diversity in nature unknown. We
      constructed B. thailandensis strains that differed only in the BcpA-CT and BcpI
      proteins they produced. When co-cultured on agar, these strains each participated
      in CDI and the outcome of the competition depended on both CDI system efficiency
      and relative bacterial numbers initially. Strains also participated in CDI during
      biofilm development, resulting in pillar structures that were composed of only a
      single BcpA-CT/BcpI type. Moreover, a strain producing BcpA-CT/BcpI proteins of
      one type was prevented from joining a pre-established biofilm community composed
      of bacteria producing BcpA-CT/BcpI proteins of a different type, unless it also
      produced the BcpI protein of the established strain. Bacteria can therefore use
      CDI systems for kind recognition and competitive exclusion of 'non-self' bacteria
      from a pre-established biofilm. Our data indicate that CDI systems function in
      both cooperative and competitive behaviors to build microbial communities that
      are composed of only bacteria that are related via their CDI system alleles. 

PMID- 24743838
TI  - Determination of tissue thermal conductivity by measuring and modeling
      temperature rise induced in tissue by pulsed focused ultrasound.
AB  - A tissue thermal conductivity (Ks) is an important parameter which knowledge is
      essential whenever thermal fields induced in selected organs are predicted. The
      main objective of this study was to develop an alternative ultrasonic method for
      determining Ks of tissues in vitro suitable for living tissues. First, the method
      involves measuring of temperature-time T(t) rises induced in a tested tissue
      sample by a pulsed focused ultrasound with measured acoustic properties using
      thermocouples located on the acoustic beam axis. Measurements were performed for
      20-cycle tone bursts with a 2 MHz frequency, 0.2 duty-cycle and 3 different
      initial pressures corresponding to average acoustic powers equal to 0.7 W, 1.4 W
      and 2.1 W generated from a circular focused transducer with a diameter of 15 mm
      and f-number of 1.7 in a two-layer system of media: water/beef liver. Measurement
      results allowed to determine position of maximum heating located inside the beef
      liver. It was found that this position is at the same axial distance from the
      source as the maximum peak-peak pressure calculated for each nonlinear beam
      produced in the two-layer system of media. Then, the method involves modeling of
      T(t) at the point of maximum heating and fitting it to the experimental data by
      adjusting Ks. The averaged value of Ks determined by the proposed method was
      found to be 0.5+/-0.02 W/(m. degrees C) being in good agreement with values
      determined by other methods. The proposed method is suitable for determining Ks
      of some animal tissues in vivo (for example a rat liver). 

PMID- 24743837
TI  - beta1-integrin-dependent migration of microglia in response to neuron-released
      alpha-synuclein.
AB  - Chronic neuroinflammation is an integral pathological feature of major
      neurodegenerative diseases. The recruitment of microglia to affected brain
      regions and the activation of these cells are the major events leading to disease
      associated neuroinflammation. In a previous study, we showed that neuron-released
      alpha-synuclein can activate microglia through activating the Toll-like receptor
      2 (TLR2) pathway, resulting in proinflammatory responses. However, it is not
      clear whether other signaling pathways are involved in the migration and
      activation of microglia in response to neuron-released alpha-synuclein. In the
      current study, we demonstrated that TLR2 activation is not sufficient for all of
      the changes manifested by microglia in response to neuron-released alpha
      synuclein. Specifically, the migration of and morphological changes in microglia,
      triggered by neuron-released alpha-synuclein, did not require the activation of
      TLR2, whereas increased proliferation and production of cytokines were strictly
      under the control of TLR2. Construction of a hypothetical signaling network using
      computational tools and experimental validation with various peptide inhibitors
      showed that beta1-integrin was necessary for both the morphological changes and
      the migration. However, neither proliferation nor cytokine production by
      microglia was dependent on the activation of beta1-integrin. These results
      suggest that beta1-integrin signaling is specifically responsible for the
      recruitment of microglia to the disease-affected brain regions, where neurons
      most likely release relatively high levels of alpha-synuclein. 

PMID- 24743839
TI  - Syphilis and its correlates among heterosexual males attending sexually
      transmitted infection clinics - observation from a multicity cohort in Jiangsu
      Province, China.
AB  - OBJECTIVES: To estimate the prevalence of HIV and syphilis, incidence of syphilis
      and to identify the correlates of syphilis infection among heterosexual male
      attendees of sexually transmitted infection (STI) clinics (MSC). METHODS: A
      cohort study of one-year duration was conducted in Yangzhou and Changzhou cities
      in Jiangsu province of China. The baseline survey commenced in June 2009,
      recruited 1225 consenting adult MSCs (609 in Yangzhou and 617 in Changzhou)
      through STI-clinic based convenience sampling. RESULTS: Baseline HIV and syphilis
      prevalence were 0.49% and 17.29% respectively. Syphilis incidence rate was 7.22
      per 100 person-years (6.53 in Yangzhou and 7.76 in Changzhou) during the 6-month
      follow-up with retention fractions of 27.38% and 35.15% for Yangzhou and
      Changzhou respectively. Majority of the participants were middle-aged, high
      school educated, married, living with partners and non-migrants. Very few
      subjects reported recent and consistent condom-use with regular partners.
      Although considerable number of MSCs reported recent sexual exposure with female
      sex workers (FSW) and non-FSW casual partners, the proportion of reported condom
      use was very low during those exposures. In multivariate analyses higher age,
      having recent sex with FSWs and being HIV-positive were associated with higher
      syphilis sero-positivity while higher education was protective. In bivariate
      analyses, being married, divorced/widowed, official residency of the study cities
      and non-use of condom with regular partners predicted higher risk. CONCLUSIONS:
      Considering the potential bridging role of MSCs between high and low-risk
      populations, effective intervention strategies among them targeting the
      correlates of syphilis infection are urgently called for in Jiangsu province of
      China.

PMID- 24743841
TI  - A ZigBee-based location-aware fall detection system for improving elderly
      telecare.
AB  - Falls are the primary cause of accidents among the elderly and frequently cause
      fatal and non-fatal injuries associated with a large amount of medical costs.
      Fall detection using wearable wireless sensor nodes has the potential of
      improving elderly telecare. This investigation proposes a ZigBee-based location
      aware fall detection system for elderly telecare that provides an unobstructed
      communication between the elderly and caregivers when falls happen. The system is
      based on ZigBee-based sensor networks, and the sensor node consists of a
      motherboard with a tri-axial accelerometer and a ZigBee module. A wireless sensor
      node worn on the waist continuously detects fall events and starts an indoor
      positioning engine as soon as a fall happens. In the fall detection scheme, this
      study proposes a three-phase threshold-based fall detection algorithm to detect
      critical and normal falls. The fall alarm can be canceled by pressing and holding
      the emergency fall button only when a normal fall is detected. On the other hand,
      there are three phases in the indoor positioning engine: path loss survey phase,
      Received Signal Strength Indicator (RSSI) collection phase and location
      calculation phase. Finally, the location of the faller will be calculated by a k
      nearest neighbor algorithm with weighted RSSI. The experimental results
      demonstrate that the fall detection algorithm achieves 95.63% sensitivity, 73.5%
      specificity, 88.62% accuracy and 88.6% precision. Furthermore, the average error
      distance for indoor positioning is 1.15 +/- 0.54 m. The proposed system
      successfully delivers critical information to remote telecare providers who can
      then immediately help a fallen person. 

PMID- 24743842
TI  - A survey of the perception of comprehensiveness among dentists in a large
      Brazilian city.
AB  - OBJECTIVES: To quantitatively identify the perception of dentists regarding
      comprehensiveness and its domains of "patient welcoming", "bonding" and "quality
      of care" in primary dental care settings of a large Brazilian city. METHODS: A
      questionnaire was administered to all dentists comprising the primary health care
      service to Belo Horizonte with tenured jobs and 40 work hours per week, totalling
      a population of 207 professionals. The response rate was 90.34%. A pilot test was
      conducted with 44 dentists working in primary care for at least two years and who
      did not participate in the main study. Descriptive statistical analysis involved
      calculating proportions. No confidence intervals were calculated because this was
      a census study. RESULTS: In most items (79.0%), professionals' perceptions about
      the comprehensiveness were overwhelmingly positive. When we stratified the
      analysis by domain and checked those items about which dentists had a less
      favourable perception, 22.7% were in the patient welcoming domain, 25.0% were in
      the bonding domain and 12.5% were in quality of care. CONCLUSIONS:
      Comprehensiveness, as an approach in health care practice, needs to be enhanced,
      and there is evidence that these dentists are aware of its importance.

PMID- 24743843
TI  - Design of a real-time and continua-based framework for care guideline
      recommendations.
AB  - Telehealth is an important issue in the medical and healthcare domains. Although
      a number of systems have been developed to meet the demands of emerging
      telehealth services, the following problems still remain to be addressed: (1)
      most systems do not monitor/predict the vital signs states so that they are able
      to send alarms to caregivers in real-time; (2) most systems do not focus on
      reducing the amount of work that caregivers need to do, and provide patients with
      remote care; and (3) most systems do not recommend guidelines for caregivers.
      This study thus proposes a framework for a real-time and Continua-based Care
      Guideline Recommendation System (Cagurs) which utilizes mobile device platforms
      to provide caregivers of chronic patients with real-time care guideline
      recommendations, and that enables vital signs data to be transmitted between
      different devices automatically, using the Continua standard. Moreover, the
      proposed system adopts the episode mining approach to monitor/predict anomalous
      conditions of patients, and then offers related recommended care guidelines to
      caregivers so that they can offer preventive care in a timely manner. 

PMID- 24743840
TI  - Genome-wide diet-gene interaction analyses for risk of colorectal cancer.
AB  - Dietary factors, including meat, fruits, vegetables and fiber, are associated
      with colorectal cancer; however, there is limited information as to whether these
      dietary factors interact with genetic variants to modify risk of colorectal
      cancer. We tested interactions between these dietary factors and approximately
      2.7 million genetic variants for colorectal cancer risk among 9,287 cases and
      9,117 controls from ten studies. We used logistic regression to investigate
      multiplicative gene-diet interactions, as well as our recently developed Cocktail
      method that involves a screening step based on marginal associations and gene
      diet correlations and a testing step for multiplicative interactions, while
      correcting for multiple testing using weighted hypothesis testing. Per quartile
      increment in the intake of red and processed meat were associated with
      statistically significant increased risks of colorectal cancer and vegetable,
      fruit and fiber intake with lower risks. From the case-control analysis, we
      detected a significant interaction between rs4143094 (10p14/near GATA3) and
      processed meat consumption (OR = 1.17; p = 8.7E-09), which was consistently
      observed across studies (p heterogeneity = 0.78). The risk of colorectal cancer
      associated with processed meat was increased among individuals with the rs4143094
      TG and -TT genotypes (OR = 1.20 and OR = 1.39, respectively) and null among those
      with the GG genotype (OR = 1.03). Our results identify a novel gene-diet
      interaction with processed meat for colorectal cancer, highlighting that diet may
      modify the effect of genetic variants on disease risk, which may have important
      implications for prevention.

PMID- 24743844
TI  - Comparing the Visual Analogue Scale and the Pediatric Quality of Life Inventory
      for measuring health-related quality of life in children with oral clefts.
AB  - OBJECTIVES: To evaluate the performance of the Visual Analogue Scale (VAS), in
      measuring overall health-related Quality of Life (HRQoL) in children with oral
      clefts relative to the Pediatric Quality of Life Inventory 4.0 (PedsQLTM) Generic
      Core Scales, one of the most validated and commonly used methods to measure
      pediatric HRQoL. METHODS: The study included a population-based sample of 307
      children aged 5 to 10 years who were born in Iowa, New York, and Arkansas with
      non-syndromic oral clefts. Data on HRQoL were obtained using a VAS and PedsQLTM
      via self-administered interviews with the parents. We evaluated the correlations
      between the VAS and PedsQLTM total scores, and the correlations of each of these
      two scales with a series of child health and wellbeing indicators. RESULTS: The
      VAS and PedsQLTM scores were well-correlated (r = 0.67). There were no prominent
      differences between the correlations of VAS and PedsQLTM with the selected
      indicators of child health and wellbeing; differences in correlations were less
      than 0.1. Differences in HRQoL by cleft type were more pronounced on the
      PedsQLTM. CONCLUSIONS: Our study finds the VAS to perform relatively well in
      measuring overall HRQoL among children with oral clefts. The VAS may be useful as
      a screening tool to identify children with oral clefts at risk of low HRQoL for
      referral into more comprehensive evaluations and for measuring average HRQoL
      across a sample of children.

PMID- 24743845
TI  - Developing a new electromyography-based algorithm to diagnose the etiology of
      fecal incontinence.
AB  - PURPOSE: For surface electromyography (sEMG) to become widely used in fecal
      incontinence (FI) etiology assessment, one would have to create a simple, step-by
      step, computer-aided, electromyography-based algorithm that would become the
      basis for a computer-aided diagnosis (CAD) system. Thus, the aim of this work was
      to develop such an algorithm. METHODS: Each patient included in the study
      underwent a structured medical interview, a general physical examination, and a
      proctological examination. Patients that scored more than 10 points on the fecal
      incontinence severity index (FISI) underwent further tests that included
      rectoscopy, anorectal manometry, transanal ultrasonography, multichannel sEMG,
      and assessment of anal reflexes. Patients with fully diagnosed FI were included
      into the study group. The control group consisted of healthy volunteers that
      scored five or less points on the FISI and had no known anal sphincters
      dysfunction. RESULTS: Forty-nine patients were qualified to the study group (age
      +/- SD 58.9 +/- 13.8). The control group was number- and gender-matched (age +/-
      SD 45.4 +/- 15.1). The sensitivity and specificity of classification tree number
      I, to diagnose neurogenic FI, were 89.5 and 86 %, respectively. For patients with
      idiopathic FI, these values were 82 and 91 %, respectively. The sensitivity and
      specificity of classification tree number III, to diagnose neurogenic FI, were 84
      and 78 %, respectively. For patients with idiopathic FI, these values were 78 and
      87 %, respectively. CONCLUSIONS: The relative simplicity and low classification
      costs allow to assume that algorithms based on classification trees I and III
      will serve to be the basis for a FI etiology CAD system.

PMID- 24743846
TI  - Microscopic colitis: clinical characteristics, treatment and outcomes in an Irish
      population.
AB  - BACKGROUND AND AIMS: Many aspects of microscopic colitis remain poorly
      understood. Our aim was to report a single centre experience with this condition.
      METHODS: Two hundred and twenty-two patients (52 male, 170 female; median age 64
      years; range 32-90) diagnosed between 1993 and 2010 were studied. Medical notes
      were reviewed, and data on age, gender, clinical features, history of autoimmune
      diseases, medication use, cigarette smoking, histology and outcome were
      collected. RESULTS: There were 99 cases of lymphocytic and 123 of collagenous
      colitis. Diarrhoea was almost invariably present (98 %) while abdominal pain (24
      %), weight loss (10 %), faecal incontinence (8 %) and blood PR (5 %) were also
      described. Twenty-eight percent had concomitant autoimmune diseases, most
      commonly coeliac disease. Patients were taking a variety of medications at
      diagnosis thought to be associated with microscopic colitis including NSAIDs (22
      %), aspirin (19 %), statins (15 %), proton pump inhibitors (19 %) and SSRIs (10
      %) at diagnosis. Prior to the widespread use of budesonide in our institution, 33
      % of patients required two or more medications during therapy compared to 15 %
      following the introduction of budesonide (p = 0.001). Thirty-eight percent of
      patients achieved spontaneous remission with either no treatment or simple anti
      diarrhoeals. Using a multivariate model, the only factor associated with
      spontaneous remission was male gender (RR 1.9; 95 % CI 1.0-3.6; p = 0.04). Two
      patients had refractory microscopic colitis; one required a colectomy while a
      more recent case has responded to anti-TNFalpha therapy. CONCLUSION: Microscopic
      colitis is predominantly a benign and self-limiting disorder. The introduction of
      budesonide has revolutionised treatment of this lesser studied inflammatory bowel
      disease.

PMID- 24743847
TI  - The outcome of liver resection and lymphadenectomy for hilar lymph node
      involvement in colorectal cancer liver metastases.
AB  - OBJECTIVE: Hepatic hilar lymph node (HLN) involvement is considered as a poor
      prognostic factor during liver resection in colorectal liver metastases (CLM).
      The purpose of this study is to identify the clinical factors that distinguish
      HLN-positive patients from those who are hilar lymph node negative and to
      evaluate the frequency of macroscopic involvement of hepatic HLN, to investigate
      the impact of HLN involvement on survival after resection for CLM with
      lymphadenectomy and adjuvant chemotherapy. PATIENTS AND METHODS: Between January
      2000 and August 2012, 73 selected CLM patients underwent liver resections with
      lymphadenectomy in the Hepatopancreatobiliary Surgery Department I of Beijing
      Cancer Hospital. Clinical data, surgical outcome, and prognosis after operation
      of patients with HLN involvement were compared with that of patients without HLN
      involvement. RESULTS: Of the 73 patients who underwent liver resections with
      lymphadenectomy, 12 (16.4 %) patients had HLN involvement identified by
      pathology. Compared with patients without HLN involvement, the frequency of lymph
      nodes metastasis for primary tumor was significantly higher in HLN-positive
      patients (p = 0.023). For CLM patients with and without HLN involvement, 5-year
      overall survival (OS) was 16.2 and 37.1 %, respectively (p = 0.04). Five-year
      disease-free survival (DFS) rates were 0 and 32.9 % (p = 0.034). Multivariate
      analysis showed that involved resected HLN was an independent risk factor for
      overall survival. CONCLUSION: We should suspect HLN involvement in patients with
      colorectal cancer liver metastases when they have regional lymph nodes of primary
      tumor metastasis. Liver resection with HLN dissection might offer a unique
      curative opportunity for CLM patients with HLN involvement.

PMID- 24743848
TI  - Adenocarcinoma on j-pouch after proctocolectomy for ulcerative colitis-case
      report and review of literature.

PMID- 24743849
TI  - Baseline factors predictive of patient satisfaction with sacral neuromodulation
      for idiopathic fecal incontinence.
AB  - PURPOSE: Sacral neuromodulation (SNM) is an established treatment for fecal
      incontinence (FI). A recent study from our group found that the relationship
      between patient satisfaction and clinical outcome is complex and does not match
      the traditional used success criteria. Therefore, the ability to predict patient
      satisfaction must be given priority. The aim of the present study is to identify
      baseline factors predictive of patient satisfaction, with SNM, for idiopathic FI.
      METHODS: We analyzed data from patients treated with SNM for idiopathic FI in
      Aarhus, Denmark, and Maastricht, The Netherlands. A questionnaire considering
      self-reported satisfaction was mailed to these patients and compared to baseline
      characteristics. Logistic regression was used to determine the predictive value
      of baseline demographic and diagnostic variables. RESULTS: In total, 131 patients
      were included in the analysis. Patient satisfaction with the current treatment
      result was reported in 75 patients. Fifty-six patients were dissatisfied with SNM
      treatment, after median 46 months (range 11-122) with permanent implantation.
      Pudendal nerve terminal motor latency (PNTML) was the solely identified predictor
      for long-term patient satisfaction. A subgroup univariate-logistic regression
      analysis showed that PNTML <= 2.3 ms at the side of lead implantation was a
      statistically significant predictor for patient satisfaction (odds ratio (OR)
      2.3, 95% confidence interval (CI) 1.01-5.24, p = 0.048). CONCLUSION: Baseline
      PNTML measurement may be predictive of long-term satisfaction with SNM therapy
      for idiopathic FI. Further studies are needed to confirm this result.

PMID- 24743850
TI  - Mucosal adjuvant activity of IL-2 presenting spores of bacillus subtilis in a
      murine model of Helicobacter pylori vaccination.
AB  - The endospores of Bacillus subtilis are now widely used as a platform for
      presentation of heterologous proteins and due to their safety record and high
      resistance to harsh environmental conditions can be considered as potential
      vehicles for oral vaccination. In this research we show that recombinant B.
      subtilis spores presenting a fragment of the Helicobacter acinonychis UreB
      protein and expressing the ureB gene under vegetative promoter elicit a strong
      cellular immune response in orally immunized mice when co-administered with
      spores presenting IL-2. We show for the first time the successful application of
      two types of recombinant spores, one carrying an antigen and the other an
      adjuvant, in a single oral immunization. 

PMID- 24743851
TI  - Intracytoplasmic sperm injection using DNA-fragmented sperm in mice negatively
      affects embryo-derived embryonic stem cells, reduces the fertility of male
      offspring and induces heritable changes in epialleles.
AB  - Intracytoplasmic sperm injection (ICSI) in mice using DNA-fragmented sperm (DFS)
      has been linked to an increased risk of genetic and epigenetic abnormalities both
      in embryos and offspring. This study examines: whether embryonic stem cells
      (ESCs) derived from DFS-ICSI embryos reflect the abnormalities observed in the
      DFS-ICSI progeny; the effect of DFS-ICSI on male fertility; and whether DFS-ICSI
      induces epigenetic changes that lead to a modified heritable phenotype. DFS-ICSI
      produced embryos showed a low potential to generate ESC lines. However, these
      lines had normal karyotype accompanied by early gene expression alterations,
      though a normal expression pattern was observed after several passages. The
      fertility of males in the DFS-ICSI and control groups was compared by mating
      test. Sperm quantity, vaginal plug and pregnancy rates were significantly lower
      for the DFS-ICSI-produced males compared to in vivo-produced mice, while the
      number of females showing resorptions was higher. The epigenetic effects of DFS
      ICSI were assessed by analyzing the phenotype rendered by the Axin1Fu allele, a
      locus that is highly sensitive to epigenetic perturbations. Oocytes were injected
      with spermatozoa from Axin1Fu/+ mice and the DFS-ICSI-generated embryos were
      transferred to females. A significantly higher proportion of pups expressed the
      active kinky-tail epiallele in the DFS-ICSI group than the controls. IN
      CONCLUSION: 1) ESCs cannot be used as a model of DFS-ICSI; 2) DFS-ICSI reduces
      sperm production and fertility in the male progeny; and 3) DFS-ICSI affects the
      postnatal expression of a defined epigenetically sensitive allele and this
      modification may be inherited across generations.

PMID- 24743852
TI  - The EAPC framework on palliative sedation and clinical practice--a questionnaire
      based survey in Germany.
AB  - BACKGROUND: Palliative sedation (PS) can be offered to patients with intolerable
      symptom burden refractory to comprehensive palliative care (PC) treatment. Little
      is known about the daily practice of using PS in German specialized PC
      institutions in the context of existing national and international
      recommendations. PURPOSE: This study's primary objective is to explore how PS is
      used in German specialized PC institutions with reference to the EAPC framework.
      METHODS: The heads of all palliative care units, hospices, specialized palliative
      home care teams, and specialized pediatric palliative home care teams listed in
      the official address registers were invited to take part in a questionnaire
      survey about the clinical practice of PS in their institution. RESULTS:
      Considerable differences of the frequency of PS exist between institutions. The
      estimated frequency of PS ranges from 0 to 80 % of all patients treated per year
      (mean 6.7 %). Some PC specialists report to discuss PS as treatment option for
      every patient they encounter. Specific evaluation and documentation tools are
      rare. Of the study participants, 36.2 % are not familiar with international and
      national recommendations. CONCLUSION: Many differences exist in frequency and
      clinical handling of PS in Germany. Implementation of international and national
      recommendations into clinical practice remains inconsistent.

PMID- 24743853
TI  - Mucositis care in acute leukemia and non-Hodgkin lymphoma patients undergoing
      high-dose chemotherapy.
AB  - PURPOSE: This study intends to provide new insights into the incidence and care
      of mucositis by the epidemiological characterization of patients with
      hematological malignancy treated at our institution. It also aims to understand
      the effectiveness of several treatments used. METHODS: This is a longitudinal
      observational single-center study-convenience sample-which includes malignant
      hematologic inpatients submitted to high-dose CT from February to August 2012. We
      registered epidemiological data, diagnosis, oral mucositis daily questionnaire
      (OMDQ), World Health Organization (WHO) oral toxicity scale, and supportive
      medications used for mucositis. RESULTS: We evaluated 30 patients who had 73
      episodes of hospitalization, having recorded the development of mucositis in 21.9
      % (n = 16) episodes (22 patients with acute leukemia (AL) and 8 patients with non
      Hodgkin lymphoma (NHL)). Grades 3-4 mucositis was reported in 4.1 % of the total
      episodes. The results of OMDQ showed some limitations in the quality of life, of
      patients with mucositis, related with the ability to eat and drink due to mouth
      pain (p < 0.001). In patients with NHL and AL, neutropenia entails an increased
      risk of mucositis (p < 0.001). Patients who did not initiate early prophylaxis
      with conservative measures developed mucositis earlier (p < 0.05). CONCLUSIONS:
      The incidence of mucositis is high, being reported mainly in AL patients, with
      limitations in quality of life. Grade 4 neutropenia increases mucositis risk.
      Early prophylaxis with basic oral care may delay mucositis. Further studies are
      crucial to characterize mucositis epidemiology, physiopathology, and its
      management.

PMID- 24743854
TI  - The development and implementation of a volunteer lay navigation competency
      framework at an outpatient cancer center.
AB  - PURPOSE: To describe the development and delivery of a competency framework
      designed to guide the recruitment, training, and competency screening of
      volunteer lay navigators at an outpatient cancer centre in Victoria, BC. METHODS:
      Volunteers that passed a screening interview underwent 22 h of training focusing
      on the scope of the navigator's role, communication skills, and cancer center
      processes and resources. Volunteers that passed a post-training interview, by
      demonstrating a basic level of competency in three domains (Self as Navigator,
      Communication, and Knowledge/Information), were invited to participate as
      volunteer lay navigators in a three-step intervention with newly diagnosed lung
      cancer patients at the British Columbia Cancer Agency-Vancouver Island Centre.
      RESULTS: Of the 27 volunteers who attended a screening interview, 20 were invited
      to participate in training. From the subset of 20, 13 of these participants
      achieved competency scores high enough to qualify them to practice as volunteer
      lay navigators. CONCLUSIONS: By incorporating the lessons we have learned from
      this study, we believe that the lay navigation competency framework serves as a
      useful model for selecting, training, and supporting competent navigators.

PMID- 24743856
TI  - CT and MRI of coronary artery disease: established and emerging applications.

PMID- 24743857
TI  - Expert opinion: how and when to perform cardiac magnetic resonance myocardial T1
      mapping.

PMID- 24743858
TI  - Prevalence and antimicrobial resistance of porcine O157 and non-O157 Shiga toxin
      producing Escherichia coli from India.
AB  - The aims of this study were to determine the prevalence of Shiga toxin-producing
      Escherichia coli (STEC) strains in pigs as a possible STEC reservoir in India as
      well as to characterize the STEC strains and to determine the antimicrobial
      resistance pattern of the strains. A total of 782 E. coli isolates from
      clinically healthy (n = 473) and diarrhoeic piglets (309) belonging to major pig
      producing states of India were screened by the polymerase chain reaction (PCR)
      assay for the presence of virulence genes characteristic for STEC, that is, Shiga
      toxin-producing gene(s) (stx1, stx2), intimin (eae), enterohemolysin (hlyA) and
      STEC autoagglutinating adhesin (Saa). Overall STEC were detected in 113 (14.4%)
      piglets, and the prevalence of E. coli O157 and non-O157 STEC were 4 (0.5%) and
      109 (13.9%), respectively. None of the O157 STEC isolates carried gene encoding
      for H7 antigen (fliCh7). The various combinations of virulence genes present in
      the strains studied were stx1 in 4.6%, stx1 in combination with stx2 gene in
      5.1%, stx1 in combination with stx2 and ehxA in 0.6%, stx1 in combination with
      stx2 and eae in 0.2% and stx2 alone in 3.7%. All STEC isolates were found
      negative for STEC autoagglutinating adhesin (Saa). The number of STEC isolates
      which showed resistance to antimicrobials such as ampicillin, tetracycline,
      streptomycin, lincomycin, nalidixic acid, sulfadiazine, penicillin, gentamicin,
      kanamycin and ceftriaxone were 100, 99, 98, 97, 95, 94, 92, 88, 85 and 85,
      respectively. Ninety-seven isolates showed resistance to more than 2
      antimicrobials, and 8 resistance groups (R1 to R8) were observed. This study
      demonstrates that pigs in India harbour both O157 and non-O157 STEC, and this may
      pose serious public health problems in future.

PMID- 24743859
TI  - Evaluation of bovine rumen contents as a feed for lambs.
AB  - This study evaluated effects of increasing levels of dried rumen contents (DRC)
      on voluntary intake, growth performance, digestibility, nutritive value, N
      utilization, microbial protein supply (MPS), and purine derivatives excretion
      (PDE) of lambs fed with Afzelia africana basal forage. Sixteen lambs (13.7 +/-
      0.1 kg body weight (BW)) were randomly assigned to one of the four eight diets
      containing 0, 200, 400 and 600 g DRC/kg dry matter (DM) in a completely random
      design. Intakes of concentrate, DM, crude protein (CP), organic matter (OM),
      digestible CP (DCP), digestible OM (DOM), digestible energy (DE) and
      metabolizable energy (ME), CP and OM digestibility, DOM, DCP, DE, ME, N intake
      and retention, weight gain, cost/kg BW gain, MPS and PDE increased with
      increasing DRC level up to 400 g/kg DRC and declined at 600 g/kg DRC (P < 0.05;
      0.01). Feed conversion ratio and DM digestibility declined as DRC level increased
      from 0 to 400 g/kg and peaked at 600 g/kg DRC (P < 0.05; 0.01). Forage intake and
      DE/DCP ratio decreased (P < 0.05; 0.01) progressively with increasing DRC level.
      Results indicate that DRC can be incorporated up to 400 g/kg in a compounded
      ration for sheep.

PMID- 24743863
TI  - Inflammatory molecular signature associated with infectious agents in psychosis.
AB  - Schizophrenia (SZ) is a devastating mental condition with onset in young
      adulthood. The identification of molecular biomarkers that reflect illness
      pathology is crucial. Recent evidence suggested immune and inflammatory cascades
      in conjunction with infection may play a role in the pathology. To address this
      question, we investigated molecular changes in cerebrospinal fluid (CSF) from
      antipsychotic-naive patients with SZ and at risk mental status for psychosis
      (ARMS), in comparison with healthy controls (HCs). We measured 90 analytes using
      a broad multiplex platform focusing on immune and inflammatory cascades then
      selected 35 with our quality reporting criteria for further analysis. We also
      examined Toxoplasma gondii (TG) and herpes simplex virus 1 antibody levels in
      CSF. We report that expression of 15 molecules was significantly altered in the
      patient groups (SZ and ARMS) compared with HCs. The majority of these molecular
      changes (alpha-2-macroglobulin [alpha2M], fibrinogen, interleukin-6 receptor [IL
      6R], stem cell factor [SCF], transforming growth factor alpha [TGFalpha], tumor
      necrosis factor receptor 2 [TNFR2], IL-8, monocyte chemotactic protein 2 [MCP
      2/CCL8], testosterone [for males], angiotensin converting enzyme [ACE], and
      epidermal growth factor receptor) were consistent between SZ and ARMS patients,
      suggesting these may represent trait changes associated with psychotic conditions
      in general. Interestingly, many of these analytes (alpha2M, fibrinogen, IL-6R,
      SCF, TGFalpha, TNFR2, IL-8, MCP-2/CCL8, and testosterone [for males]) were
      exacerbated in subjects with ARMS compared with subjects with SZ. Although
      further studies are needed, we optimistically propose that these molecules may be
      good candidates for predictive markers for psychosis from an early stage. Lastly,
      reduction of IL-6R, TGFalpha, and ACE was correlated with positivity of TG
      antibody in the CSF, suggesting possible involvement of TG infection in the
      pathology. 

PMID- 24743866
TI  - Lack of orthostatic symptoms in dementia patients with orthostatic hypotension.
AB  - PURPOSE: Orthostatic hypotension (OH) is common and increases with age. OH is
      part of the autonomic dysfunction in dementia with Lewy bodies (DLB). Commonly OH
      is diagnosed when the patient falls which is a risk factor of premature death.
      Our objective was to systematically investigate the clinical symptoms associated
      with measurement of OH in different neurodegenerative dementias and normal
      controls (NC). METHODS: 154 patients [50 DLB, 50 Alzheimer's disease (AD), 54 AD
      and vascular components (ADvasc)] were examined with systolic and diastolic blood
      pressure measurements in supine position, immediately after standing up and after
      1, 3, 5 and 10 min of standing. They were compared with 50 NC. Orthostatic
      symptoms were registered according to a predefined protocol. RESULTS: Twenty
      seven percent of all the investigated individuals reported OH symptoms during the
      measurement while 43% fulfilled the criteria of OH. Sixty-three percent of
      orthostatic patients did not have any symptoms during the measurement. The
      prevalence of any orthostatic symptoms during the measurement differed
      significantly (p < 0.001) between the diagnostic groups with 40% in DLB patients,
      37% in ADvasc, 28% in AD and 2% in NC. The most frequent symptom was dizziness
      13.7%. CONCLUSIONS: Classical orthostatic symptoms are absent in the majority of
      dementia patients with OH. The orthostatic reaction must therefore be routinely
      measured in this patient group. This is particularly important for patients with
      DLB where falls as a result of OH are common.

PMID- 24743864
TI  - Why do bad things happen to me? Attributional style, depressed mood, and
      persecutory delusions in patients with schizophrenia.
AB  - Theoretical models postulate an important role of attributional style (AS) in the
      formation and maintenance of persecutory delusions and other positive symptoms of
      schizophrenia. However, current research has gathered conflicting findings. In a
      cross-sectional design, patients with persistent positive symptoms of
      schizophrenia (n = 258) and healthy controls (n = 51) completed a revised version
      of the Internal, Personal and Situational Attributions Questionnaire (IPSAQ-R)
      and assessments of psychopathology. In comparison to controls, neither patients
      with schizophrenia in general nor patients with persecutory delusions (n = 142)
      in particular presented an externalizing and personalizing AS. Rather, both
      groups showed a "self-blaming" AS and attributed negative events more toward
      themselves. Persecutory delusions were independently predicted by a personalizing
      bias for negative events (beta = 0.197, P = .001) and by depression (beta =
      0.152, P = .013), but only 5% of the variance in persecutory delusions could be
      explained. Cluster analysis of IPSAQ-R scores identified a "personalizing" (n =
      70) and a "self-blaming" subgroup (n = 188), with the former showing slightly
      more pronounced persecutory delusions (P = .021). Results indicate that patients
      with schizophrenia and patients with persecutory delusions both mostly blamed
      themselves for negative events. Nevertheless, still a subgroup of patients could
      be identified who presented a more pronounced personalizing bias and more severe
      persecutory delusions. Thus, AS in patients with schizophrenia might be less
      stable but more determined by individual and situational characteristics that
      need further elucidation. 

PMID- 24743867
TI  - Pediatric euthanasia in Belgium: disturbing developments.

PMID- 24743868
TI  - Renal artery stenosis-when to screen, what to stent?
AB  - Renal artery stensosis (RAS) continues to be a problem for clinicians, with no
      clear consensus on how to investigate and assess the clinical significance of
      stenotic lesions and manage the findings. RAS caused by fibromuscular dysplasia
      is probably commoner than previously appreciated, should be actively looked for
      in younger hypertensive patients and can be managed successfully with
      angioplasty. Atheromatous RAS is associated with increased incidence of
      cardiovascular events and increased cardiovascular mortality, and is likely to be
      seen with increasing frequency. Evidence from large clinical trials has led
      clinicians away from recommending interventional revascularisation towards
      aggressive medical management. There is now interest in looking more closely at
      patient selection for intervention, with focus on intervening only in patients
      with the highest-risk presentations such as flash pulmonary oedema, rapidly
      declining renal function and severe resistant hypertension. The potential
      benefits in terms of improving hard cardiovascular outcomes may outweigh the
      risks of intervention in this group, and further research is needed. 

PMID- 24743869
TI  - The expression analysis of LATS2 gene in de novo AML patients.
AB  - Acute myeloid leukemia is a heterogeneous disease with respect to presentation
      and clinical outcome. Acquired genetic alterations along with epigenetic changes
      in hematopoietic progenitor cells are associated with the disease development.
      LATS2, as a tumor suppressor, has been indicated to have expression variations in
      different cancers. The aim of the present study was to analyze the expression
      level of the LATS2 gene in acute myeloid leukemia (AML) patients. Using
      quantitative real-time PCR, the expression level of the LATS2 gene was detected
      in peripheral blood samples from 32 patients with de novo AML and 10 normal
      controls. LATS2 gene was significantly over-expressed in AML patients compared to
      normal subjects. Significant LATS2 over-expression was observed in all FAB types
      except for the M3 (p = 0.661). The present work provides the first evidence of
      the over-expression of LATS2 in AML patients and suggests that the gene might
      play a role in the disease development and hence may be a potential therapeutic
      target for AML treatment.

PMID- 24743870
TI  - Standard intensive chemotherapy is less effective and far more toxic than
      attenuated induction and post-induction regimen in elderly patients with acute
      myeloid leukemia.
AB  - The open-label, prospective study aimed to evaluate the efficacy and safety for
      standard intensive chemotherapy compared with attenuated therapy in elderly
      patients with acute myeloid leukemia (AML). A total of 297 patients between 65
      and 82 years were enrolled in the study. The 141 patients received standard-dose
      therapy (daunorubicin 45 mg/m(2) * 3 days with cytarabine 100 mg/m(2) * 7 days
      for induction therapy, while post-induction therapy consisted of high-dose
      cytarabine 1.5 g/m(2) * 4 days), and the attenuated treatment (daunorubicin 30
      mg/m(2) * 3 days with cytarabine 75 mg/m(2) * 7 days for induction therapy, while
      post-induction therapy consisted of attenuated high-dose Ara-C 1.0 g/m(2) * 3
      days) was administered to the remaining 156 patients, based on a random number
      assigned. Total 168 patients (56.6%) achieved complete remission with an
      incomplete blood recovery (CR)/CRi. No significant differences were observed
      between the two treatments (P = 0.60). Attenuated chemotherapy improved overall
      survival (OS) and progression-free survival (PFS) compared to standard-dose
      therapy; 5-year OS values for these two groups were 39 and 24 months,
      respectively (P < 0.001), and the PFS values for these two groups were 35 versus
      23 months (P < 0.001). In addition, the attenuated treatment with a poor risk
      profile overcame the negative impact and yielded OS and PFS values similar to
      those of the standard-dose chemotherapy with a better-to-intermediate risk
      profile. Five-year OS values for these two groups were 28 versus 28 months (P =
      0.89), and the 5-year PFS values were 27 and 28 months, respectively (P = 0.89).
      The most common adverse drug effect for chemotherapy was agranulocytosis (98.3%).
      There was a significant difference in early mortality between the attenuated and
      standard-dose treatment groups (0.64% vs. 7.1%, respectively, P < 0.01). Standard
      intensive chemotherapy is less effective and far more toxic than attenuated
      induction and post-induction regimen in elderly patients with AML.

PMID- 24743871
TI  - Low expression of insulin-like growth factor binding protein 7 associated with
      poor prognosis in human glioma.
AB  - OBJECTIVES: To investigate insulin-like growth factor binding protein 7 (IGFBP7)
      mRNA levels in human glioma and normal brain tissue, and to determine their
      clinical significance. METHODS: In this retrospective study, IGFBP7 mRNA was
      quantified by real-time reverse transcription-polymerase chain reaction in brain
      tissue samples from patients with glioma and normal control subjects. Kaplan
      Meier and Cox proportional hazards analyses were performed to determine any
      clinical and prognostic associations. RESULTS: IGFBP7 mRNA levels were
      significantly lower in glioma tissue (n = 120) than in normal brain tissue (n =
      20). Low (i.e. below the median, 5.9) IGFBP7 mRNA levels were significantly
      associated with larger tumour size (>= 5 cm, compared with <5 cm, diameter).
      Patients with high (above median) IGFBP7 had longer overall survival than those
      with low IGFBP7. Tumour grade and IGFBP7 mRNA level were independent predictors
      of overall survival. CONCLUSIONS: IGFBP7 downregulation is associated with poor
      prognosis in glioma, and this molecule may represent both a prognostic marker and
      a potential therapeutic target.

PMID- 24743872
TI  - Duloxetine in the treatment of burning mouth syndrome refractory to conventional
      treatment: A case report.
AB  - Patients with burning mouth syndrome (BMS) report burning sensation and pain
      involving the tongue and oral mucosa without any apparent medical or dental
      cause. The pathogenesis of this syndrome remains unclear and there is currently
      no standard treatment. BMS is, therefore, often misdiagnosed and its management
      is complex. This lack of clinical expertise may result in decreased health
      related quality of life and increased psychological distress among patients with
      BMS. The present case report involves a 77-year-old female patient with BMS
      refractory to conventional treatment with nerve block and medication, who was
      successfully treated with duloxetine. Duloxetine may become a new therapeutic
      option in the management of BMS. 

PMID- 24743873
TI  - Effect of intravenous general anaesthesia with epidural block on the expression
      of pre-endogenous opioid peptide genes.
AB  - OBJECTIVE: To measure the plasma concentrations of three endogenous opioid
      peptides and the levels of preproenkephalin (PPE) and preprodynorphin (PPD) mRNA
      in peripheral blood lymphocytes of patients during scheduled surgery performed
      under intravenous general anaesthesia combined with an epidural block. METHODS:
      Patients were anaesthetized and arterial blood was collected at 0 (baseline), 20,
      40, 60, and 80 min during surgery. The plasma concentrations of beta-endorphin,
      leucine-enkephalin and dynorphin A were measured using radioimmunoassay. Reverse
      transcription-polymerase chain reaction was used to measure the levels of PPD and
      PPE mRNA in peripheral blood lymphocytes collected during surgery. RESULTS:
      Fifteen patients participated in this prospective study. The plasma
      concentrations of beta-endorphin were significantly lower at all time-points
      compared with the baseline value. The plasma concentrations of leucine-enkephalin
      and dynorphin A were significantly lower at 40, 60, and 80 min compared with
      baseline. The PPD/beta-actin ratio was significantly lower at 80 min compared
      with baseline, while the PPE/beta-actin ratio showed no significant change.
      CONCLUSION: The level of mRNA from two pre-endogenous opioid peptide genes either
      decreased or remained unchanged during surgery under intravenous general
      anaesthesia with epidural block, suggesting that patients remained pain free
      during surgery.

PMID- 24743874
TI  - Association between obesity, prostate-specific antigen level and prostate
      specific antigen density in men with a negative prostate biopsy.
AB  - OBJECTIVE: To determine the association between body mass index (BMI), serum
      prostate-specific antigen (PSA) level and PSA density (PSAD) in patients with an
      elevated serum PSA level but a negative prostate biopsy. METHODS: This
      retrospective study enrolled men with a negative prostate biopsy but a serum PSA
      level of 3.0-10 ng/ml. All men underwent anthropometric measurements, serum PSA
      determination and transrectal ultrasound examination. BMI was grouped according
      to the Asia-Pacific obesity criteria: nonobese (<25 kg/m(2)) versus obese (>= 25
      kg/m(2)). Partial correlation and linear regression models between PSA, PSAD and
      BMI were conducted after adjusting for age. RESULTS: A total of 907 men were
      enrolled in this study. On multivariate analyses, PSA showed no significant
      correlation with age or BMI, whereas PSAD had a negative correlation with age and
      BMI. Similar results were obtained when patients were categorized as having low
      (3.0 < PSA  <= 6.5 ng/ml) or high PSA (6.5 < PSA <= 10.0 ng/ml) levels.
      CONCLUSION: PSAD, but not PSA, demonstrated a significant negative correlation
      with BMI. This indicates that a new strategy including PSAD rather than simple
      PSA levels should be adopted in the study of obesity-adjusted PSA cut-offs.

PMID- 24743875
TI  - Fibrates and risk of cancer in tissues with high PPAR-alpha concentration: a
      nested case-control study.
AB  - BACKGROUND: Fibrates are lipid-lowering agents that act as peroxisome
      proliferator-activated receptor (PPAR)-alpha agonists. They have been associated
      with cancers in experimental models, but data in humans are rare, and among
      published studies none has investigated cancers in tissues with high PPAR-alpha
      concentrations. METHODS: A nested case-control study was performed in a French
      population-based healthcare database. Adults aged >=45 years, and free of cancer
      for 3 years, were followed for 5 years for incident cases of melanoma, non
      melanoma skin cancers, thyroid, pancreas, bladder, and kidney cancers. Cases were
      matched with up to ten controls for age, sex, and diseases that could increase
      the risk of cancers. Conditional logistic models, adjusted for drug-use as
      potential confounders, were used to estimate the risk (odds ratio [OR]) of
      cancers of interest (and individual cancers) associated with cumulative exposure
      to fibrates (defined daily doses [DDD]). RESULTS: Among the 147,338 eligible
      subjects, 3,331 (2.3 %) cases of studied cancers were identified. Only use of
      fibrates >550 DDDs was associated with an increased risk (OR 1.26; 95 % CI 1.12
      1.42), and similar results were found for statins (>=1,460 DDDs; OR 1.15; 95 % CI
      1.03-1.28). When considering cancers individually, the association was
      significant for non-melanoma skin-cancer (OR 1.35; 95 % CI 1.14-1.60), and close
      to significance for bladder cancer (OR 1.26; 95 % CI 0.96-1.64); similar
      associations with the use of statins were found. CONCLUSIONS: The associations
      found between fibrate exposure and cancers of tissues with high PPAR-alpha
      concentrations were most likely related to residual confounding as similar
      associations were found for statins.

PMID- 24743876
TI  - Association of statin use with sleep disturbances: data mining of a spontaneous
      reporting database and a prescription database.
AB  - BACKGROUND: Particular interest has been generated regarding the possible
      influence of statin use on sleep quality. However, no conclusive evidence exists
      that a particular statin is more likely to be associated with sleep disturbances
      versus others. It remains uncertain whether different statins produce different
      risks for sleep disturbance. OBJECTIVE: To examine the association between statin
      use and the risk of sleep disturbances, we conducted data mining using the US
      Food and Drug Administration Adverse Event Reporting System (FAERS) and a large
      organized database of prescriptions constructed by a database vendor (Japan
      Medical Information Research Institute, Inc. Japan). METHODS: Relevant reports in
      the FAERS were identified and analyzed. Data from the first quarter of 2004
      through the end of 2012 [corrected] were included in this study.The reporting
      odds ratio (ROR) was used to detect spontaneous report signals, calculated using
      the case/non-case method. For the ROR, a signal was detected if the lower limit
      of 95 % two-sided confidence interval (95 % CI) was >1. Additionally, signal
      detection using the IC was conducted using the IC025 metric, a lower limit of the
      95 % CI of the IC, where a signal is detected if the IC025 value exceeds 0. In
      addition, symmetry analysis was used to identify the risk of insomnia after using
      statins over the period of January 2006 to August 2013. RESULTS: In the analyses
      of the FAERS database, significant signals for sleep disturbances including
      disturbances in initiating and maintaining sleep, sleep disorders NEC, sleeping
      disorders due to a general medical condition, and parasomnias were found. In the
      prescription sequence symmetry analysis, a significant association between statin
      use and hypnotic drug use was found, with adjusted sequence ratios of 1.14 (1.03
      1.26), 1.20 (1.11-1.29), and 1.18 (1.11-1.25) at intervals of 91, 182, and 365
      days, respectively. CONCLUSION: Multi-methodological approaches using different
      algorithms and databases strongly suggest that statin use is associated with an
      increased risk for sleep disturbances including insomnia.

PMID- 24743877
TI  - Mortality from and incidence of pesticide poisoning in South Korea: findings from
      National Death and Health Utilization Data between 2006 and 2010.
AB  - Pesticide poisoning has been recognized as an important public health issue
      around the world. The objectives of this study were to report nationally
      representative figures on mortality from and the incidence of pesticide poisoning
      in South Korea and to describe their epidemiologic characteristics. We calculated
      the age-standardized rates of mortality from and the incidence of pesticide
      poisoning in South Korea by gender and region from 2006 through 2010 using
      registered death data obtained from Statistics Korea and national healthcare
      utilization data obtained from the National Health Insurance Review and
      Assessment Service of South Korea. During the study period of 2006 through 2010,
      a total of 16,161 deaths and 45,291 patients related to pesticide poisoning were
      identified, marking respective mortality and incidence rates of 5.35 and 15.37
      per 100,000 population. Intentional self-poisoning was identified as the major
      cause of death due to pesticides (85.9%) and accounted for 20.8% of all recorded
      suicides. The rates of mortality due to and incidence of pesticide poisoning were
      higher in rural than in urban areas, and this rural-urban discrepancy was more
      pronounced for mortality than for incidence. Both the rate of mortality due to
      pesticide poisoning and its incidence rate increased with age and were higher
      among men than women. This study provides the magnitude and epidemiologic
      characteristics for mortality from and the incidence of pesticide poisoning at
      the national level, and strongly suggests the need for further efforts to prevent
      pesticide self-poisonings, especially in rural areas in South Korea. 

PMID- 24743878
TI  - The altitudinal patterns of leaf C?N?P stoichiometry are regulated by plant
      growth form, climate and soil on Changbai Mountain, China.
AB  - Understanding the geographic patterns and potential drivers of leaf stoichiometry
      is critical for modelling the nutrient fluxes of ecosystems and to predict the
      responses of ecosystems to global changes. This study aimed to explore the
      altitudinal patterns and potential drivers of leaf C?N?P stoichiometry. We
      measured the concentrations of leaf C, N and P in 175 plant species as well as
      soil nutrient concentrations along an altitudinal transect (500-2300 m) on the
      northern slope of Changbai Mountain, China to explore the response of leaf C?N?P
      stoichiometry to plant growth form (PGF), climate and soil. Leaf C, N, P and
      C?N?P ratios showed significant altitudinal trends. In general, leaf C and C?N?P
      ratios increased while leaf N and P decreased with elevation. Woody and
      herbaceous species showed different responses to altitudinal gradients. Trees had
      the largest variation in leaf C, C?N and C?P ratios, while herbs showed the
      largest variation in leaf N, P and N?P ratio. PGF, climate and soil jointly
      regulated leaf stoichiometry, explaining 17.6% to 52.1% of the variation in the
      six leaf stoichiometric traits. PGF was more important in explaining leaf
      stoichiometry variation than soil and climate. Our findings will help to
      elucidate the altitudinal patterns of leaf stoichiometry and to model ecosystem
      nutrient cycling. 

PMID- 24743879
TI  - Ethnic variations in severe maternal morbidity in the UK- a case control study.
AB  - BACKGROUND: Previous studies showed a higher risk of maternal morbidity amongst
      black and other minority ethnic (BME) groups, but were unable to investigate
      whether this excess risk was concentrated within specific BME groups in the UK.
      Our aim was to analyse the specific risks and to investigate reasons for any
      disparity. METHODS: Unmatched case-control analysis using data from the United
      Kingdom Obstetric Surveillance System (UKOSS), February 2005-January 2013. Cases
      were 1,753 women who experienced severe morbidity during the peripartum period.
      Controls were 3,310 women who delivered immediately before the cases in the same
      hospital. Multivariable logistic regression modelling was used to adjust for
      known confounders and to understand their effects. RESULTS: Compared with white
      European women, the odds of severe maternal morbidity were 83% higher among black
      African women (adjusted odds ratio (aOR) = 1.83; 95% Confidence Interval (CI) =
      1.39-2.40), 80% higher among black Caribbean (aOR = 1.80; 95% CI = 1.14-2.82),
      74% higher in Bangladeshi (aOR = 1.74; 95% CI = 1.05-2.88), 56% higher in other
      non-whites (non-Asian) (aOR = 1.56; 95% CI = 1.05-2.33) and 43% higher among
      Pakistani women (aOR = 1.43; 95% CI = 1.07-1.92). There was no evidence of
      substantial confounding. Anaemia in current pregnancy, previous pregnancy
      problems, inadequate utilisation of antenatal care, pre-existing medical
      conditions, parity>3, and being younger and older were independent risk factors
      but, the odds of severe maternal morbidity did not differ by socioeconomic
      status, between smokers and non-smokers or by BMI. DISCUSSION: This national
      study demonstrates an increased risk of severe maternal morbidity among women of
      ethnic minority backgrounds which could not be explained by known risk factors
      for severe maternal morbidity.

PMID- 24743881
TI  - Myocyte renewal and therapeutic myocardial regeneration using various progenitor
      cells.
AB  - Whereas the demand on effective treatment options for chronic heart failure is
      dramatically increasing, the recent recognition of physiological and pathological
      myocyte turnover in the adult human heart provided a fundamental basis for the
      therapeutic regeneration. Divergent modalities were experimentally introduced to
      this field, and selected ones have been applied clinically; the history began
      with skeletal myoblasts and bone-marrow-derived cells, and lately mesenchymal
      stem/stromal cells and resident cardiac cells joined the repertoire. Among them,
      autologous transplantation of c-kit-positive cardiac stem cells in patients with
      chronic ventricular dysfunction resulted in an outstanding outcome with long
      lasting effects without increasing major adverse events. To further optimize
      currently available approaches, we have to consider multiple factors, such as the
      targeting disease, the cell population and number to be administered, and the
      timing and the route of cell delivery. Exploration of the consequence of the
      previous clinical trials would allow us to envision an ideal cellular therapy for
      various cardiovascular disorders. 

PMID- 24743880
TI  - Exposure-dependent control of malaria-induced inflammation in children.
AB  - In malaria-naive individuals, Plasmodium falciparum infection results in high
      levels of parasite-infected red blood cells (iRBCs) that trigger systemic
      inflammation and fever. Conversely, individuals in endemic areas who are
      repeatedly infected are often asymptomatic and have low levels of iRBCs, even
      young children. We hypothesized that febrile malaria alters the immune system
      such that P. falciparum re-exposure results in reduced production of pro
      inflammatory cytokines/chemokines and enhanced anti-parasite effector responses
      compared to responses induced before malaria. To test this hypothesis we used a
      systems biology approach to analyze PBMCs sampled from healthy children before
      the six-month malaria season and the same children seven days after treatment of
      their first febrile malaria episode of the ensuing season. PBMCs were stimulated
      with iRBC in vitro and various immune parameters were measured. Before the
      malaria season, children's immune cells responded to iRBCs by producing pro
      inflammatory mediators such as IL-1beta, IL-6 and IL-8. Following malaria there
      was a marked shift in the response to iRBCs with the same children's immune cells
      producing lower levels of pro-inflammatory cytokines and higher levels of anti
      inflammatory cytokines (IL-10, TGF-beta). In addition, molecules involved in
      phagocytosis and activation of adaptive immunity were upregulated after malaria
      as compared to before. This shift was accompanied by an increase in P. falciparum
      specific CD4+Foxp3- T cells that co-produce IL-10, IFN-gamma and TNF; however,
      after the subsequent six-month dry season, a period of markedly reduced malaria
      transmission, P. falciparum-inducible IL-10 production remained partially
      upregulated only in children with persistent asymptomatic infections. These
      findings suggest that in the face of P. falciparum re-exposure, children acquire
      exposure-dependent P. falciparum-specific immunoregulatory responses that dampen
      pathogenic inflammation while enhancing anti-parasite effector mechanisms. These
      data provide mechanistic insight into the observation that P. falciparum-infected
      children in endemic areas are often afebrile and tend to control parasite
      replication. 

PMID- 24743882
TI  - Acute retinal necrosis associated with Epstein-Barr virus: immunohistopathologic
      confirmation.
AB  - IMPORTANCE: Acute retinal necrosis (ARN) is an infectious retinitis primarily
      caused by the herpesviruses. Although the Epstein-Barr virus (EBV) has been
      implicated as a cause of ARN, to our knowledge, there has been no histopathologic
      documentation. We report the clinical history and histopathologic confirmation
      that EBV can cause ARN. OBSERVATIONS: Clinical course and histopathology of a
      patient diagnosed with ARN caused by infection with EBV confirmed by molecular
      pathology. CONCLUSIONS AND RELEVANCE: Epstein-Barr virus is a recognized cause of
      intraocular inflammation and has been implicated as a possible cause of ARN.
      However, to our knowledge, tissue demonstration of EBV in a patient with ARN has
      not previously been reported. We identified the organism in the necrotic retina
      of a patient receiving immunosuppression because of idiopathic pulmonary
      fibrosis.

PMID- 24743883
TI  - Minor changes in soil bacterial and fungal community composition occur in
      response to monsoon precipitation in a semiarid grassland.
AB  - Arizona and New Mexico receive half of their annual precipitation during the
      summer monsoon season, making this large-scale rain event critical for ecosystem
      productivity. We used the monsoon rains to explore the responses of soil
      bacterial and fungal communities to natural moisture pulses in a semiarid
      grassland. Through 454 pyrosequencing of the 16S rRNA gene and ITS region, we
      phylogenetically characterized these communities at 22 time points during a
      summer season. Relative humidity increased before the rains arrived, creating
      conditions in soil that allowed for the growth of microorganisms. During the
      course of the study, the relative abundances of most bacterial phyla showed
      little variation, though some bacterial populations responded immediately to an
      increase in soil moisture once the monsoon rains arrived. The Firmicutes phylum
      experienced over a sixfold increase in relative abundance with increasing water
      availability. Conversely, Actinobacteria, the dominant taxa at our site, were
      negatively affected by the increase in water availability. No relationship was
      found between bacterial diversity and soil water potential. Bacterial community
      structure was unrelated to all environmental variables that we measured, with the
      exception of a significant relationship with atmospheric relative humidity.
      Relative abundances of fungal phyla fluctuated more throughout the season than
      bacterial abundances did. Variation in fungal community structure was unrelated
      to soil water potential and to most environmental variables. However, ordination
      analysis showed a distinct fungal community structure late in the season,
      probably due to plant senescence. 

PMID- 24743884
TI  - Nitrogen-cycling genes in epilithic biofilms of oligotrophic high-altitude lakes
      (central Pyrenees, Spain).
AB  - Microbial biofilms in oligotrophic environments are the most reactive component
      of the ecosystem. In high-altitude lakes, exposed bedrock, boulders, gravel, and
      sand in contact with highly oxygenated water and where a very thin epilithic
      biofilm develops usually dominate the littoral zone. Traditionally, these
      surfaces have been considered unsuitable for denitrification, but recent
      investigations have shown higher biological diversity than expected, including
      diverse anaerobic microorganisms. In this study, we explored the presence of
      microbial N-cycling nirS and nirK (denitrification through the conversion of NO2(
      ) to NO), nifH (N2 fixation), anammox (anaerobic ammonium oxidation), and amoA
      (aerobic ammonia oxidation, both bacterial and archaeal) genes in epilithic
      biofilms of a set of high-altitude oligotrophic lakes in the Pyrenees. The
      concentrations of denitrifying genes determined by quantitative PCR were two
      orders of magnitude higher than those of ammonia-oxidizing genes. Both types of
      genes were significantly correlated, suggesting a potential tight coupling
      nitrification-denitrification in these biofilms that deserves further
      confirmation. The nifH gene was detected after nested PCR, and no signal was
      detected for the anammox-specific genes used. The taxonomic composition of
      denitrifying and nitrogen-fixing genes was further explored by cloning and
      sequencing. Interestingly, both microbial functional groups were richer and more
      genetically diverse than expected. The nirK gene, mostly related to
      Alphaproteobacteria (Bradyrhizobiaceae), dominated the denitrifying gene pool as
      expected for oxygen-exposed habitats, whereas Deltaproteobacteria (Geobacter
      like) and Cyanobacteria were the most abundant among nitrogen fixers. Overall,
      these results suggest an epilithic community more metabolically diverse than
      previously thought and with the potential to carry out an active role in the
      biogeochemical nitrogen cycling of high-altitude ecosystems. Measurements of
      activity rates should be however carried out to substantiate and further explore
      these findings.

PMID- 24743885
TI  - Effect of red clay on diesel bioremediation and soil bacterial community.
AB  - Red clay is a type of soil, the red color of which results from the presence of
      iron oxide. It is considered an eco-friendly material, with many industrial,
      cosmetic, and architectural uses. A patented method was applied to red clay in
      order to change its chemical composition and mineral bioavailability. The
      resulting product was designated processed red clay. This study evaluates the
      novel use of red clay and processed red clay as biostimulation agents in diesel
      contaminated soils. Diesel biodegradation was enhanced in the presence of red
      clay and processed red clay by 4.9- and 6.7-fold, respectively, and the number of
      culturable bacterial cells was correlated with the amount of diesel
      biodegradation. The growth of Acinetobacter oleivorans DR1, Pseudomonas putida
      KT2440, and Cupriavidus necator was promoted by both types of red clays. Culture
      independent community analysis determined via barcoded pyrosequencing indicated
      that Nocardioidaceae, Xanthomonadaceae, Pseudomonadaceae, and Caulobacteraceae
      were enriched by diesel contamination. Bacterial strain isolation from
      naphthalene- and liquid paraffin-amended media was affiliated with enriched taxa
      based on 16S rRNA gene sequence identity. We suggest that the biostimulating
      mechanism of red clay and processed red clay is able to support bacterial growth
      without apparent selection for specific bacterial species. 

PMID- 24743886
TI  - Gibberellin application at pre-bloom in grapevines down-regulates the expressions
      of VvIAA9 and VvARF7, negative regulators of fruit set initiation, during
      parthenocarpic fruit development.
AB  - Fruit set is initiated only after fertilization and is tightly regulated
      primarily by gibberellins (GAs) and auxins. The application of either of these
      hormones induces parthenocarpy, fruit set without fertilization, but the
      molecular mechanism underlying this induction is poorly understood. In the
      present study, we have shown that the parthenocarpic fruits induced by GA
      application at pre-bloom result from the interaction of GA with auxin signaling.
      The transcriptional levels of the putative negative regulators of fruit set
      initiation, including Vitis auxin/indole-3-acetic acid transcription factor 9
      (VvIAA9), Vitis auxin response factor 7 (VvARF7), and VvARF8 were monitored
      during inflorescence development in seeded diploid 'Tamnara' grapevines with or
      without GA application. Without GA application, VvIAA9, VvARF7, and VvARF8 were
      expressed at a relatively high level before full bloom, but decreased thereafter
      following pollination. After GA application at 14 days before full bloom (DBF);
      however, the expression levels of VvIAA9 and VvARF7 declined at 5 DBF prior to
      pollination. The effects of GA application on auxin levels or auxin signaling
      were also analyzed by monitoring the expression patterns of auxin biosynthesis
      genes and auxin-responsive genes with or without GA application. Transcription
      levels of the auxin biosynthesis genes Vitis anthranilate synthase beta subunit
      (VvASB1-like), Vitis YUCCA2 (VvYUC2), and VvYUC6 were not significantly changed
      by GA application. However, the expressions of Vitis Gretchen Hagen3.2 (VvGH3.2)
      and VvGH3.3, auxin-responsive genes, were up-regulated from 2 DBF to full bloom
      with GA application. Furthermore, the Vitis GA signaling gene, VvDELLA was up
      regulated by GA application during 12 DBF to 7 DBF, prior to down-regulation of
      VvIAA9 and VvARF7. These results suggest that VvIAA9 and VvARF7 are negative
      regulators of fruit set initiation in grapevines, and GA signaling is integrated
      with auxin signaling via VvDELLA during parthenocarpic fruit development in
      grapevines.

PMID- 24743887
TI  - Three-dimensional microstructural properties of nanofibrillated cellulose films.
AB  - Nanofibrillated cellulose (NFC) films have potential as oxygen barriers for,
      e.g., food packaging applications, but their use is limited by their hygroscopic
      characteristics. The three-dimensional microstructure of NFC films made of Pinus
      radiata (Radiata Pine) kraft pulp fibres has been assessed in this study,
      considering the structural development as a function of relative humidity (RH).
      The surface roughness, micro-porosity, thickness and their correlations were
      analyzed using X-ray microtomography (X-MUCT) and computerized image analysis.
      The results are compared to those from scanning electron microscopy and laser
      profilometry. Based on a series of films having varying amounts of 2,2,6,6
      tetramethylpiperidinyl-1-oxyl (TEMPO)-mediated oxidated nanofibrils, it was
      demonstrated that X-MUCT is suitable for assessing the surface and bulk 3D
      microstructure of the cellulose films. Additionally, one of the series was
      assessed at varying humidity levels, using the non-destructive capabilities of X
      MUCT and a newly developed humidity chamber for in-situ characterization. The
      oxygen transmission rate (OTR) of the films (20 g=m2) was below 3:7 mL m-2 day-1
      at humidity levels below 60% RH. However, the OTR increased considerably to 12:4
      mL m-2 day-1 when the humidity level increased to 80% RH. The increase in OTR was
      attributed to a change of the film porosity, which was reflected as an increase
      in local thickness. Hence, the characterization techniques applied in this study
      shed more light on the structures of NFC films and how they are affected by
      varying humidity levels. It was demonstrated that in increasing relative humidity
      the films swelled and the oxygen barrier properties decreased.

PMID- 24743888
TI  - The effects of the CCR6/CCL20 biological axis on the invasion and metastasis of
      hepatocellular carcinoma.
AB  - Chemokines and their receptors have recently been shown to play major roles in
      cancer metastasis. Chemokine receptor 6 (CCR6) and its ligand, CCL20, were highly
      expressed in a variety of human cancers. In our present study, we aimed to
      clarify whether CCR6/CCL20 was correlated with the migration of hepatocellular
      carcinoma (HCC). RT-PCR and Western blot results showed that CCR6 was
      overexpressed in different invasive potential HCC cell lines (p<0.05), while the
      expression of CCL20 had no obvious difference (p>0.05). CCR6 was suppressed by
      siRNA in HCCLM6, and then the biological behaviors of HCCLM6 cells were observed.
      The results showed that the CCR6/CCL20 biological axis increased the capacity of
      proliferation and adhesion, as well as the chemotactic migration and the level of
      cytokines related to degraded extracellular matrix. In conclusion, these findings
      indicate that CCR6 indeed participates in regulating the migration and invasion
      of HCC, and it might become a prognostic factor of HCC.

PMID- 24743889
TI  - The role of pericytes in neurovascular unit remodeling in brain disorders.
AB  - Neurons are extremely vulnerable cells that tightly rely on the brain's highly
      dynamic and complex vascular network that assures an accurate and adequate
      distribution of nutrients and oxygen. The neurovascular unit (NVU) couples
      neuronal activity to vascular function, controls brain homeostasis, and maintains
      an optimal brain microenvironment adequate for neuronal survival by adjusting
      blood-brain barrier (BBB) parameters based on brain needs. The NVU is a
      heterogeneous structure constituted by different cell types that includes
      pericytes. Pericytes are localized at the abluminal side of brain microvessels
      and contribute to NVU function. Pericytes play essential roles in the development
      and maturation of the neurovascular system during embryogenesis and stability
      during adulthood. Initially, pericytes were described as contractile cells
      involved in controlling neurovascular tone. However, recent reports have shown
      that pericytes dynamically respond to stress induced by injury upon brain
      diseases, by chemically and physically communicating with neighboring cells, by
      their immune properties and by their potential pluripotent nature within the
      neurovascular niche. As such, in this paper, we would like to review the role of
      pericytes in NVU remodeling, and their potential as targets for NVU repair
      strategies and consequently neuroprotection in two pathophysiologically distinct
      brain disorders: ischemic stroke and Alzheimer's disease (AD). 

PMID- 24743890
TI  - Functional analysis of the dioxin response elements (DREs) of the murine CYP1A1
      gene promoter: beyond the core DRE sequence.
AB  - The aryl hydrocarbon receptor (AhR) is a ligand-dependent transcription factor
      that mediates the biological and toxicological effects of halogenated aromatic
      hydrocarbons, such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). When activated
      by dioxin, the cytosolic AhR protein complex translocates into the nucleus and
      dimerizes with the ARNT (Ah receptor nuclear translocator) protein. The
      heteromeric ligand:AhR/Arnt complex then recognizes and binds to its specific DNA
      recognition site, the dioxin response element (DRE). DREs are located upstream of
      cytochrome P4501A1 (CYP1A1) and other AhR-responsive genes, and binding of the
      AhR complex stimulates their transcription. Although CYP1A1 expression has been
      used as the model system to define the biochemical and molecular mechanism of AhR
      action, there is still limited knowledge about the roles of each of the seven
      DREs located in the CYP1A1 promoter. These seven DREs are conserved in mouse,
      human and rat. Deletion analysis showed that a single DRE at -488 was enough to
      activate the transcription. Truncation analysis demonstrated that the DRE at site
      -981 has the highest transcriptional efficiency in response to TCDD. This result
      was verified by mutation analysis, suggesting that the conserved DRE at site -981
      could represent a significant and universal AhR regulatory element for CYP1A1.
      The reversed substituted intolerant core sequence (5'-GCGTG-3' or 5'-CACGC-3') of
      seven DREs reduced the transcriptional efficiency, which illustrated that the
      adjacent sequences of DRE played a vital role in activating transcription. The
      core DRE sequence (5'-TNGCGTG-3') tends to show a higher transcriptional level
      than that of the core DRE sequence (5'-CACGCNA-3') triggered by TCDD.
      Furthermore, in the core DRE (5'-TNGCGTG-3') sequence, when "N" is thymine or
      cytosine (T or C), the transcription efficiency was stronger compared with that
      of the other nucleotides. The effects of DRE orientation, DRE adjacent sequences
      and the nucleotide "N" in the core DRE (5'-TNGCGTG-3') sequence on the AhR
      regulated CYP1A1 transcription in response to TCDD were studied systematically,
      and our study laid a good foundation for further investigation into the AhR
      dependent transcriptional regulation triggered by dioxin and dioxin-like
      compounds. 

PMID- 24743891
TI  - Effects of a protic ionic liquid on the reaction pathway during non-aqueous sol
      gel synthesis of silica: a Raman spectroscopic investigation.
AB  - The reaction pathway during the formation of silica via a two-component "non
      aqueou" sol-gel synthesis is studied by in situ time-resolved Raman spectroscopy.
      This synthetic route is followed with and without the addition of the protic
      ionic liquid 1-ethylimidazolium bis(trifluoromethanesulfonyl)imide (C2HImTFSI) in
      order to investigate its effect on the reaction pathway. We demonstrate that
      Raman spectroscopy is suitable to discriminate between different silica
      intermediates, which are produced and consumed at different rates with respect to
      the point of gelation. We find that half-way to gelation monomers and shorter
      chains are the most abundant silica species, while the formation of silica rings
      strongly correlates to the sol-to-gel transition. Thus, curling up of linear
      chains is here proposed as a plausible mechanism for the formation of small
      rings. These in turn act as nucleation sites for the condensation of larger rings
      and thus the formation of the open and polymeric silica network. We find that the
      protic ionic liquid does not change the reaction pathway per se, but accelerates
      the cyclization process, intermediated by the faster inclusion of monomeric
      species. 

PMID- 24743892
TI  - The reliability and predictive ability of a biomarker of oxidative DNA damage on
      functional outcomes after stroke rehabilitation.
AB  - We evaluated the reliability of 8-hydroxy-2'-deoxyguanosine (8-OHdG), and
      determined its ability to predict functional outcomes in stroke survivors. The
      rehabilitation effect on 8-OHdG and functional outcomes were also assessed. Sixty
      one stroke patients received a 4-week rehabilitation. Urinary 8-OHdG levels were
      determined by liquid chromatography-tandem mass spectrometry. The test-retest
      reliability of 8-OHdG was good (interclass correlation coefficient=0.76). Upper
      limb motor function and muscle power determined by the Fugl-Meyer Assessment
      (FMA) and Medical Research Council (MRC) scales before rehabilitation showed
      significant negative correlation with 8-OHdG (r=-0.38, r=-0.30; p<0.05). After
      rehabilitation, we found a fair and significant correlation between 8-OHdG and
      FMA (r=-0.34) and 8-OHdG and pain (r=0.26, p<0.05). Baseline 8-OHdG was
      significantly correlated with post-treatment FMA, MRC, and pain scores (r=-0.34, 
      0.31, and 0.25; p<0.05), indicating its ability to predict functional outcomes. 8
      OHdG levels were significantly decreased, and functional outcomes were improved
      after rehabilitation. The exploratory study findings conclude that 8-OHdG is a
      reliable and promising biomarker of oxidative stress and could be a valid
      predictor of functional outcomes in patients. Monitoring of behavioral indicators
      along with biomarkers may have crucial benefits in translational stroke research.

PMID- 24743893
TI  - The biomolecular basis of adipogenic differentiation of adipose-derived stem
      cells.
AB  - There is considerable attention regarding the role of receptor signaling and
      downstream-regulated mediators in the homeostasis of adipocytes, but less
      information is available concerning adipose-derived stem cell (ASC) biology.
      Recent studies revealed that the pathways regulating ASC differentiation involve
      the activity of receptor tyrosine kinases (RTKs), including fibroblast growth
      factor, vascular endothelial growth factor, ErbB receptors and the downstream
      regulated serine/threonine protein kinase B (Akt) and phosphatase and tensin
      homolog (PTEN) activity. RTKs are cell surface receptors that represent key
      regulators of cellular homeostasis but also play a critical role in the
      progression of cancer. Many of the metabolic effects and other consequences of
      activated RTKs are mediated by the modulation of Akt and extracellular signal
      regulated protein kinases 1 (Erk-1) signaling. Akt activity sustains survival and
      the adipogenic differentiation of ASCs, whereas Erk-1 appears downregulated. The
      inhibition of FGFR-1, EGFR and ErbB2 reduced proliferation, but only FGFR-1
      inihibition reduced Akt activity and adipogenesis. Adipogenesis and
      neovascularization are also chronologically and spatially coupled processes and
      RTK activation and downstream targets are also involved in ASC-mediated
      angiogenesis. The potentiality of ASCs and the possibility to modulate specific
      molecular pathways underlying ASC biological processes and, in particular, those
      shared with cancer cells, offer new exciting strategies in the field of
      regenerative medicine. 

PMID- 24743894
TI  - MALDI Q-TOF CID MS for diagnostic ion screening of human milk oligosaccharide
      samples.
AB  - Human milk oligosaccharides (HMO) represent the bioactive components of human
      milk, influencing the infant's gastrointestinal microflora and immune system.
      Structurally, they represent a highly complex class of analyte, where the main
      core oligosaccharide structures are built from galactose and N-acetylglucosamine,
      linked by 1-3 or 1-4 glycosidic linkages and potentially modified with fucose and
      sialic acid residues. The core structures can be linear or branched. Additional
      structural complexity in samples can be induced by endogenous exoglycosidase
      activity or chemical procedures during the sample preparation. Here, we show that
      using matrix-assisted laser desorption/ionization (MALDI) quadrupole-time-of
      flight (Q-TOF) collision-induced dissociation (CID) as a fast screening method,
      diagnostic structural information about single oligosaccharide components present
      in a complex mixture can be obtained. According to sequencing data on 14 out of
      22 parent ions detected in a single high molecular weight oligosaccharide
      chromatographic fraction, 20 different oligosaccharide structure types,
      corresponding to over 30 isomeric oligosaccharide structures and over 100
      possible HMO isomers when biosynthetic linkage variations were taken into
      account, were postulated. For MS/MS data analysis, we used the de novo sequencing
      approach using diagnostic ion analysis on reduced oligosaccharides by following
      known biosynthetic rules. Using this approach, de novo characterization has been
      achieved also for the structures, which could not have been predicted. 

PMID- 24743895
TI  - Silencing DACH1 promotes esophageal cancer growth by inhibiting TGF-beta
      signaling.
AB  - Human Dachshund homologue 1 (DACH1) is a major component of the Retinal
      Determination Gene Network. Loss of DACH1 expression was found in breast,
      prostate, lung, endometrial, colorectal and hepatocellular carcinoma. To explore
      the expression, regulation and function of DACH1 in human esophageal cancer, 11
      esophageal cancer cell lines, 10 cases of normal esophageal mucosa, 51 cases of
      different grades of dysplasia and 104 cases of primary esophageal squamous cancer
      were employed. Methylation specific PCR, immunohistochemistry, western blot, flow
      cytometry, small interfering RNAs, colony formation techniques and xenograft mice
      model were used. We found that DACH1 expression was regulated by promoter region
      hypermethylation in esophageal cancer cell lines. 18.8% (6 of 32) of grade 1,
      42.1% (8 of 19) of grade 2 and grade 3 dysplasia (ED2,3), and 61.5% (64 of 104)
      of esophageal cancer were methylated, but no methylation was found in 10 cases of
      normal esophageal mucosa. The methylation was increased in progression tendency
      during esophageal carcinogenesis (P<0.01). DACH1 methylation was associated with
      poor differentiation (P<0.05) and late tumor stage (P<0.05). Restoration of DACH1
      expression inhibited cell growth and activated TGF-beta signaling in KYSE150 and
      KYSE510 cells. DACH1 suppressed human esophageal cancer cell tumor growth in
      xenograft mice. In conclusion, DACH1 is frequently methylated in human esophageal
      cancer and methylation of DACH1 is involved in the early stage of esophageal
      carcinogenesis. DACH1 expression is regulated by promoter region
      hypermethylation. DACH1 suppresses esophageal cancer growth by activating TGF
      beta signaling.

PMID- 24743896
TI  - The effect of high-fat--high-fructose diet on skeletal muscle mitochondrial
      energetics in adult rats.
AB  - PURPOSE: To study the effect of isoenergetic administration to adult rats of high
      fat or high-fat--high-fructose diet for 2 weeks on skeletal muscle mitochondrial
      energetic. METHODS: Body and skeletal muscle composition, energy balance, plasma
      lipid profile and glucose tolerance were measured, together with mitochondrial
      functionality, oxidative stress and antioxidant defense. RESULTS: Rats fed high
      fat--high-fructose diet exhibited significantly higher plasma triglycerides and
      non-esterified fatty acids, together with significantly higher plasma glucose and
      insulin response to glucose load. Skeletal muscle triglycerides and ceramide were
      significantly higher in rats fed high-fat--high-fructose diet. Skeletal muscle
      mitochondrial energetic efficiency and uncoupling protein 3 content were
      significantly higher, while adenine nucleotide translocase content was
      significantly lower, in rats fed high-fat or high-fat--high-fructose diet.
      CONCLUSIONS: The results suggest that a high-fat--high-fructose diet even without
      hyperphagia is able to increase lipid flow to skeletal muscle and mitochondrial
      energetic efficiency, with two detrimental effects: (a) energy sparing that
      contributes to the early onset of obesity and (b) reduced oxidation of fatty
      acids and lipid accumulation in skeletal muscle, which could generate insulin
      resistance.

PMID- 24743897
TI  - Genetics of valvular heart disease.
AB  - Valvular heart disease is associated with significant morbidity and mortality and
      often the result of congenital malformations. However, the prevalence is
      increasing in adults not only because of the growing aging population, but also
      because of improvements in the medical and surgical care of children with
      congenital heart valve defects. The success of the Human Genome Project and major
      advances in genetic technologies, in combination with our increased understanding
      of heart valve development, has led to the discovery of numerous genetic
      contributors to heart valve disease. These have been uncovered using a variety of
      approaches including the examination of familial valve disease and genome-wide
      association studies to investigate sporadic cases. This review will discuss these
      findings and their implications in the treatment of valvular heart disease.

PMID- 24743899
TI  - Aortic valve repair: indications and outcomes.
AB  - Aortic valve replacement has traditionally been the treatment of choice for
      patients with aortic valve insufficiency with or without aortic root pathology.
      Aortic valve repair is emerging as an attractive treatment alternative that
      avoids the long-term risks associated with prosthetic valve implantation
      including thromboembolism, endocarditis, prosthetic valve deterioration, and
      anticoagulation related hemorrhage. Important achievements in this discipline
      have occurred over the past decade including development and refinement of valve
      preserving aortic root replacement techniques, development of a classification
      system for aortic insufficiency, surgical approaches to cusp disease with varying
      cusp anatomy. As surgical techniques for aortic valve repair continue to evolve,
      clinical outcomes up to and beyond the first decade are promising with excellent
      survival and low risk of valve related events.

PMID- 24743898
TI  - Towards a molecular systems model of coronary artery disease.
AB  - Coronary artery disease (CAD) is a complex disease driven by myriad interactions
      of genetics and environmental factors. Traditionally, studies have analyzed only
      1 disease factor at a time, providing useful but limited understanding of the
      underlying etiology. Recent advances in cost-effective and high-throughput
      technologies, such as single nucleotide polymorphism (SNP) genotyping,
      exome/genome/RNA sequencing, gene expression microarrays, and metabolomics assays
      have enabled the collection of millions of data points in many thousands of
      individuals. In order to make sense of such 'omics' data, effective analytical
      methods are needed. We review and highlight some of the main results in this
      area, focusing on integrative approaches that consider multiple modalities
      simultaneously. Such analyses have the potential to uncover the genetic basis of
      CAD, produce genomic risk scores (GRS) for disease prediction, disentangle the
      complex interactions underlying disease, and predict response to treatment.

PMID- 24743900
TI  - Ischemic heart disease and the Mediterranean diet.
AB  - Lifestyle modification is primary in cardiovascular (CV) disease prevention. A
      major contribution is the Mediterranean diet (MedDiet), defined by two of seven
      components. Italian investigators determined a significant decrease in peripheral
      arterial disease of 56 % for a high score. Multiple specific CV risk factors are
      also favorably modified by the MedDiet. This includes beneficial effect on
      inflammation, vascular endothelium, and insulin resistance. There is also
      evidence that coronary heart disease, diabetes mellitus, and metabolic syndrome
      are decreased. Benefit appears to extend to new migrants in France. The economics
      of dietary adherence are favorable with decreased total lifetime health costs.
      Although mixed nuts appear to be a major factor in the MedDiet, special emphasis
      goes to extra virgin olive oil. Benefit also extends to other noncommunicable
      diseases with a decrease in cancer, Parkinson's disease, and Alzheimer's disease.
      Further quantitation of benefit and understanding of mechanisms involved in
      dietary benefit is essential.

PMID- 24743901
TI  - Reducing the risk of infection for transrectal prostate biopsy with povidone
      iodine: a systematic review and meta-analysis.
AB  - PURPOSE: To evaluate the efficacy of povidone-iodine (PI) in reducing the risk of
      infectious complications following transrectal prostate biopsy (TRPB). METHODS:
      Eligible randomized controlled trials (RCTs) were identified from electronic
      databases (Cochrane CENTRAL, MEDLINE, and EMBASE). The database search, quality
      assessment, and data extraction were performed independently by two reviewers.
      The main outcome for the efficacy of PI was the incidence of infectious
      complications after TRPB. RESULTS: Seven trials, including 2,049 patients, met
      the inclusion criteria. Data from the seven included RCTs favored the use of PI
      before TRPB to prevent infectious complications. PI for "PI versus blank control"
      significantly reduced fever, bacteriuria, and bacteremia compared with that for
      control [relative risk (RR) 0.31; 95 % confidence interval (CI) 0.21-0.45, P <
      0.00001]. With PI versus antibiotics (ATB), patients treated with ATB alone had a
      significantly greater risk of bacteremia (RR 0.38; 95 % CI 0.16-0.90, P = 0.03).
      In "PI plus ATB versus ATB" trials, the risk of fever (RR 0.11; 95 % CI 0.02
      0.85, P = 0.03) and bacteremia (RR 0.25; 95 % CI 0.08-0.75, P = 0.01) was
      diminished in the "PI plus ATB" group. CONCLUSIONS: Rectal disinfection with PI
      provides a safe and effective method to reduce the risk of infectious
      complications following TRPB, regardless of mono-prophylaxis and combined
      prophylaxis with PI and ATB. Large, multicenter, and prospective RCTs of good
      quality trials are needed to confirm the efficacy of PI.

PMID- 24743902
TI  - Relative importance of an arbuscular mycorrhizal fungus (Rhizophagus
      intraradices) and root hairs in plant drought tolerance.
AB  - Both arbuscular mycorrhizal (AM) fungi and root hairs play important roles in
      plant uptake of water and mineral nutrients. To reveal the relative importance of
      mycorrhiza and root hairs in plant water relations, a bald root barley (brb)
      mutant and its wild type (wt) were grown with or without inoculation of the AM
      fungus Rhizophagus intraradices under well-watered or drought conditions, and
      plant physiological traits relevant to drought stress resistance were recorded.
      The experimental results indicated that the AM fungus could almost compensate for
      the absence of root hairs under drought-stressed conditions. Moreover, phosphorus
      (P) concentration, leaf water potential, photosynthetic rate, transpiration rate,
      stomatal conductance, and water use efficiency were significantly increased by R.
      intraradices but not by root hairs, except for shoot P concentration and
      photosynthetic rate under the drought condition. Root hairs even significantly
      decreased root P concentration under drought stresses. These results confirm that
      AM fungi can enhance plant drought tolerance by improvement of P uptake and plant
      water relations, which subsequently promote plant photosynthetic performance and
      growth, while root hairs presumably contribute to the improvement of plant growth
      and photosynthetic capacity through an increase in shoot P concentration. 

PMID- 24743903
TI  - Should we be doing implant-based breast reconstruction in the setting of
      radiotherapy?

PMID- 24743904
TI  - Systematic review and meta-analysis of adjuvant i(131) lipiodol after excision of
      hepatocellular carcinoma.
AB  - BACKGROUND: Curative resection for hepatocellular carcinoma (HCC) has an 80 %
      recurrence at 5 years. Survival could be prolonged with adjuvant iodine(131)
      lipiodol. This systematic review and meta-analysis was designed to assess the
      survival benefit of this treatment in patients with resected HCC compared with
      surgery alone. METHODS: Studies were identified through a systematic search of
      MEDLINE, EMBASE, PubMed, and Cochrane databases in June 2013. Three case-control
      series and two randomized, controlled trials (RCT) were included. Two of these
      studies had a second publication that analyzed long-term follow-up. Two reviewers
      extracted data with respect to disease-free and overall survival (OS). The data
      from the seven studies was then subject to meta-analysis. RESULTS: Age, sex,
      liver function, tumor size, encapsulation, microvascular invasion, multifocality,
      and the rate of major hepatic resection were similar in the two groups. Peto odds
      ratio for disease-free survival was 0.47 (95 % confidence interval (CI) 0.37
      0.59, I (2 )= 10 %) and for OS was 0.5 (95 % CI 0.39-0.64, I (2 )= 37 %), in
      favor of treatment. CONCLUSIONS: This study is limited by its comparison of two
      RCTs with three case-control studies. Most patients also had preserved liver
      function, and there was a generally low rate of microvascular invasion.
      Nonetheless, there is strong evidence for the use of adjuvant I(131) lipiodol, to
      prolong disease-free and OS, up to 5 years after resection.

PMID- 24743905
TI  - Surgical strategy for T1 gallbladder cancer: a nationwide multicenter survey in
      South Korea.
AB  - BACKGROUND: The aim of this study was to investigate the clinical features and
      clinical outcomes of T1 gallbladder (GB) cancer and to determine an appropriate
      surgical strategy for T1 GB cancer. METHODS: A nationwide multicenter study, in
      which 16 University Hospitals in Korea participated, was performed from 1995 to
      2004. A total of 258 patients, 117 patients with T1a and 141 patients with T1b
      disease were enrolled. Clinicopathologic findings and long-term follow-up results
      were analyzed after a consensus meeting of the Korean Pancreas Surgery Club was
      held. RESULTS: Simple cholecystectomy was performed in 95 patients (81.2 %) with
      T1a tumor and in 89 patients (63.1 %) with T1b tumor (p < 0.01). Lymph node
      metastasis was observed in 2.9 % of T1a patients and in 9.9 % of T1b patients (p
      = 0.391). A significant difference in 5-year disease-specific survival (DSS)
      rates was observed between T1a and T1b patients (96.4 vs 84.8 %, respectively, p
      = 0.03). However, no significant 5-year DSS rate difference was observed between
      those who underwent simple cholecystectomy or extended cholecystectomy,
      regardless of whether lymph node dissection was performed or whether lymph node
      metastasis was present. There was no significant difference in recurrence-free
      survival between simple cholecystectomy and extended cholecystectomy.
      CONCLUSIONS: There was no superiority of extended cholecystectomy over simple
      cholecystectomy in the aspect of survival and recurrence especially in T1b
      gallbladder cancer. Furthermore, the effectiveness of regional lymphadenectomy
      for treatment purpose remains questionable. Therefore, simple cholecystectomy
      could be recommended as a surgical strategy of T1 gallbladder cancer.

PMID- 24743906
TI  - Reply to 'letter to the editor of Annals of Surgical Oncology concerning "robotic
      versus open pancreatectomy: a systematic review and meta-analysis",' by
      Petrucciani Niccolo, et al. (ASO-2013-09-1427).

PMID- 24743907
TI  - Laparoscopic total colectomy with transvaginal extraction of the colon and
      ileorectal anastomosis.
AB  - BACKGROUND: The abdominal incision extraction site continues to be major source
      of morbidity after laparoscopic colectomy: mainly, incisional pain, wound
      infection, and incisional hernia. Also, in selected cases, it may delay
      initiating chemotherapy. METHODS: The video describes the technique of performing
      laparoscopic total colectomy, transvaginal removal of the entire colon, and
      intracorporeal ileorectal anastomosis in a 40-year-old woman with a sigmoid
      cancer and multiple endoscopically unresectable polyps throughout the colon.
      Computed tomography scan showed 2 liver lesions with carcinoembryonic antigen
      138. Familial adenomatous polyposis gene analysis was negative. Six trocars (one
      12 mm and five 5 mm) were used. The whole colon was removed through the
      transvaginal route. The anvil was introduced through the vagina, and circular
      stapled ileorectal anastomosis was done. RESULTS: There were no intraoperative
      complications. The operating time was 210 min. Blood loss was 20 mL. The patient
      was discharged home on postoperative day 2. Final pathology was T3N1bM1, and 2 of
      23 lymph nodes were metastatic. All polyps were tubulovillous. She was commenced
      on chemotherapy 2 weeks after surgery. At 6-month follow-up, the patient was
      doing well, had no abdominal pain, and had no vaginal discharge or dyspareunia.
      CONCLUSIONS: Natural orifice specimen extraction (NOSE) surgery can be added to
      the armamentarium of surgeons performing laparoscopic colon surgery. This
      technique may provide both an attractive way to reduce abdominal incision-related
      morbidity and a bridge to pure natural orifice transluminal endoscopic surgery
      (NOTES) colon surgery. Large-number patient data with long-term follow-up is
      needed.

PMID- 24743908
TI  - Outcome of patients undergoing salvage surgery for recurrent nasopharyngeal
      carcinoma: a meta-analysis.
AB  - BACKGROUND: The common treatment of primary patients with nasopharyngeal
      carcinoma is chemotherapy and radiotherapy. Surgery is reserved as salvage
      procedure for recurrent or persistent disease. Nevertheless, information on the
      outcome of these patients and the role of adjuvant reirradiation treatment is
      scarce. METHODS: We conducted a meta-analysis to identify prognostic factors
      associated with outcomes of patients with recurrent nasopharyngeal carcinoma
      treated by salvage surgery. RESULTS: The study group consisted of 779 patients
      from 17 published studies who met the inclusion criteria. The primary tumor
      classification at recurrence was T1-2 in 83 % of patients and T3-4 in 16.6 %.
      Regional lymph node metastases were present in 88 patients. The 5-year overall
      survival and local recurrence-free survival rates of the entire cohort were 51.2
      and 63.4 %, respectively, with a distant metastases rate of 11.3 %. The 5-year
      overall survival was 63 % in patients receiving surgery and adjuvant radiotherapy
      compared to 39 % in patients receiving surgery alone (P = 0.05). Independent
      predictors of outcome on multivariate analysis were sex, N classification,
      surgical approach (endoscopic vs. open), adjuvant treatment, and margin status.
      Both endoscopic surgery and reirradiation were independent predictors of improved
      survival. CONCLUSIONS: More than half of the patients with recurrent disease can
      be salvaged by surgery. Margins status, and N and T classification are
      significant predictors of outcome. Multivariate analysis revealed that endoscopic
      surgery offers better outcome than open surgery for T3/4 disease in selected
      patients, and adjuvant reirradiation offers an additional survival advantage over
      surgery alone.

PMID- 24743909
TI  - Prognostic impact of major receptor tyrosine kinase expression in gastric cancer.
AB  - BACKGROUND: Various kinds of molecular targeted drugs to inhibit receptor
      tyrosine kinases (RTKs) have been recently developed. The relationship between
      the expression status of major RTKs and prognosis in gastric cancer remains
      unclear. We conducted a multicenter study to evaluate the prognostic impact of
      the expression of epidermal growth factor receptor (EGFR), c-Met, platelet
      derived growth factor receptor (PDGFR), and c-Kit in gastric cancer. METHODS:
      This study included 153 gastric cancer patients who underwent gastrectomy at 9
      institutions between 2000 and 2006. Expression status of EGFR, c-Met, PDGFR, and
      c-Kit were evaluated with immunohistochemistry (IHC) centrally. Overall survival
      based on RTK expression status was statistically compared. Cox multivariate
      analysis was conducted to adjust for potentially confounding factors. RESULTS:
      The positive rates for EGFR, c-Met, PDGFR, and c-Kit were 14.4, 24.8, 41.2, and
      11.1 %, respectively. Significant interactions with expression status were
      observed for pathological N stage with EGFR; HER2-status with c-Met; tumor
      location, histology, and pathological N stage with PDGFR; and no examined
      variables with c-Kit. Concomitant HER2 positivity was observed for 0.7 % of
      tumors positive for EGFR, 3.9 % for c-Met, 4.6 % for PDGFR, and 1.3 % for c-Kit.
      There were some differences in overall survival between patients with or without
      RTK expression, but only c-Kit expression showed a significant survival
      difference in Cox multivariate analysis (P = 0.046). CONCLUSIONS: Our multicenter
      study indicated that IHC expression of 4 RTKs had some prognostic impact and that
      c-Kit-positive status may be a significant indicator of good prognosis in gastric
      cancer patients.

PMID- 24743910
TI  - A novel morphologic-molecular recurrence predictive model refines traditional
      prognostic tools for invasive breast carcinoma.
AB  - BACKGROUND: Histologic grade, TNM stage, and Nottingham Prognostic Index are
      traditional prognostic tools for breast cancer. "IHC-molecular" classification of
      breast cancer can also identify patients at different recurrence risks and
      provides insight into cancer therapy. However, cancers in each group are
      heterogeneous. A model based on the comprehensive analysis of morphologic
      features and molecular subtype was constructed to predict recurrence and refine
      these traditional prognostic tools. METHODS: Morphologic features including
      histologic grade, fibrotic focus, extensive intraductal component, lymphocytic
      infiltrate, lymphovascular invasion, tumor necrosis, tumor margin and TNM stage,
      and molecular subtypes approximated by immunohistochemistry were analyzed in 633
      patients with invasive breast carcinoma (excluding those with HER2 targeted
      therapy). Significant independent predictors for recurrence included: high
      histologic grade (p = 0.004), presence of lymphovascular invasion (p = 0.004),
      fibrotic focus (p = 0.020), mild lymphocytic infiltrate (p = 0.013), high TNM
      stage (p < 0.001), and HER2-overexpressing (p = 0.004) and basal-like (p < 0.001)
      molecular subtypes. A morphologic-molecular recurrence predictive model based on
      these features was useful in recurrence prediction, independent of treatment
      modalities, and was able to refine the traditional prognostic tools of histologic
      grade, TNM stage, and Nottingham prognostic index, particularly for intermediate
      risk groups, and to refine the luminal group molecular subtypes. Such findings
      were reproducible with a validation cohort. CONCLUSION: TNM stage, histologic
      grade, lymphovascular invasion, fibrotic focus, mild lymphocytic infiltrate, HER2
      overexpressing and basal-like molecular subtypes were important independent
      recurrence risk factors for breast cancer. This morphologic-molecular model was
      robust in recurrence prediction and refined recurrence risk stratified by the
      traditional prognostic parameters, independent of treatment modalities.

PMID- 24743911
TI  - Population-based registries are important in sarcoma: an editorial regarding
      "incidence patterns of primary bone cancer in Taiwan (2003-2010)".

PMID- 24743912
TI  - Colorectal liver metastases growth in the embolized and non-embolized liver after
      portal vein embolization: influence of initial response to induction
      chemotherapy.
AB  - PURPOSE: To compare tumor progression in both embolized and non-embolized liver
      lobes after portal vein embolization (PVE) in patients with bilobar colorectal
      liver metastases (CLM), according to the initial response to induction
      chemotherapy. METHODS: From 2002 to 2012, a total of 42 consecutive patients with
      bilobar CLM initially treated using induction chemotherapy underwent right PVE to
      achieve adequate future liver remnant volume. Tumoral and liver parenchyma
      volumes, as well as their volume variations, were measured on computed tomography
      before and after PVE in both embolized and non-embolized. Patients were
      classified as fast (<=6 cycles of induction chemotherapy) and slow (>6 cycles)
      responders. RESULTS: Overall, 432 metastases were analyzed in 42 patients.
      Patients were slow responders in 29 (69 %) cases. Tumoral volume increased in 29
      (69 %) cases in the embolized liver (+48 %; p < 0.0001), and in 28 (66 %) cases
      in the non-embolized liver (+31 %; p < 0.0001). Fast responders had a tumoral
      volume decrease in both embolized (-4 %) and non-embolized (-9 %) lobes. On the
      opposite side, slow responders had tumoral volume increase in both embolized (+79
      %) and non-embolized (+32 %) lobes. On multivariate analysis, a 'slow' response
      to induction chemotherapy was the only factor associated with tumoral progression
      in both embolized (p = 0.0012) and non-embolized (p = 0.001) lobes. CONCLUSION:
      Tumor growth after PVE is observed in both embolized and non-embolized liver
      lobes in most patients but is significantly associated with slow response to
      induction chemotherapy.

PMID- 24743913
TI  - The pregnant breast cancer patient: are we failing our most vulnerable
      population?

PMID- 24743914
TI  - Modelling technique, structural assumptions, input parameter values: which has
      the most impact on the results of a cost-effectiveness analysis?

PMID- 24743915
TI  - The diagnostic role of (18)F-FDG PET for primary central nervous system lymphoma.
AB  - OBJECTIVE: (18)F-FDG PET has become one of the most important methods for
      studying malignant lymphoma, but its diagnostic role for primary central nervous
      system lymphoma (PCNSL) has not been established. The aim of this study was to
      determine the appropriate cut-off values of FDG uptake and to investigate how
      corticosteroid administration influences PCNSL. METHODS: We retrospectively
      reviewed 82 patients with contrast-enhanced brain tumors who underwent an FDG PET
      scan at onset, including 19 PCNSLs. FDG uptake of the lesion was assessed by the
      maximum standardized uptake value (SUVmax) and the ratio of tumor to normal
      contralateral cortex activity (T/N ratio). Receiver operating characteristic
      (ROC) curves were generated from the SUVmax and T/N ratios. To investigate the
      influence of corticosteroid application before a FDG PET scan, we evaluated the
      association between the FDG uptake of the lesion and the cumulative dose of
      corticosteroid administration on 13 PCNSL patients who had received steroid
      treatment before an FDG PET examination. RESULTS: The mean FDG SUVmax and T/N
      ratio of PCNSLs were 22.6 and 2.79, respectively, and these values were
      significantly higher than those of the other malignant brain tumors. ROC analysis
      indicated that the evaluation of FDG uptake using the T/N ratio was more reliable
      than the SUVmax with respect to the differential diagnosis. When PCNSL patients
      went without steroid application before FDG PET, the accuracy of the T/N ratio
      with a cut-off point of 2.0 was 91.1%, the sensitivity was 94.7%, and the
      specificity was 87.3%. Although there are no significant differences in the FDG
      T/N ratio for PCNSL patients with or without steroid treatment, a negative
      correlation was found between the T/N ratio and cumulative dose of corticosteroid
      before PET study (r = -0.71, p = 0.032). CONCLUSIONS: We concluded that the T/N
      ratio was superior to SUVmax for FDG uptake assessment as for distinguishing
      PCNSLs from other malignant brain tumors; the appropriate T/N ratio cut-off point
      was 2.0. In addition, FDG uptake could be influenced by cumulative doses of
      corticosteroid before a PET scan, and thus this fact should be taken into
      consideration when evaluating FDG PET for PCNSL diagnosis.

PMID- 24743916
TI  - Single cell analysis reveals the stochastic phase of reprogramming to
      pluripotency is an ordered probabilistic process.
AB  - Despite years of research, the reprogramming of human somatic cells to
      pluripotency remains a slow, inefficient process, and a detailed mechanistic
      understanding of reprogramming remains elusive. Current models suggest
      reprogramming to pluripotency occurs in two-phases: a prolonged stochastic phase
      followed by a rapid deterministic phase. In this paradigm, the early stochastic
      phase is marked by the random and gradual expression of pluripotency genes and is
      thought to be a major rate-limiting step in the successful generation of induced
      Pluripotent Stem Cells (iPSCs). Recent evidence suggests that the epigenetic
      landscape of the somatic cell is gradually reset during a period known as the
      stochastic phase, but it is known neither how this occurs nor what rate-limiting
      steps control progress through the stochastic phase. A precise understanding of
      gene expression dynamics in the stochastic phase is required in order to answer
      these questions. Moreover, a precise model of this complex process will enable
      the measurement and mechanistic dissection of treatments that enhance the rate or
      efficiency of reprogramming to pluripotency. Here we use single-cell transcript
      profiling, FACS and mathematical modeling to show that the stochastic phase is an
      ordered probabilistic process with independent gene-specific dynamics. We also
      show that partially reprogrammed cells infected with OSKM follow two
      trajectories: a productive trajectory toward increasingly ESC-like expression
      profiles or an alternative trajectory leading away from both the fibroblast and
      ESC state. These two pathways are distinguished by the coordinated expression of
      a small group of chromatin modifiers in the productive trajectory, supporting the
      notion that chromatin remodeling is essential for successful reprogramming. These
      are the first results to show that the stochastic phase of reprogramming in human
      fibroblasts is an ordered, probabilistic process with gene-specific dynamics and
      to provide a precise mathematical framework describing the dynamics of
      pluripotency gene expression during reprogramming by OSKM.

PMID- 24743917
TI  - Peptide-membrane interactions of arginine-tryptophan peptides probed using quartz
      crystal microbalance with dissipation monitoring.
AB  - Membrane-active peptides include peptides that can cross cellular membranes and
      deliver macromolecular cargo as well as peptides that inhibit bacterial growth.
      Some of these peptides can act as both transporters and antibacterial agents. It
      is desirable to combine the knowledge from these two different fields of membrane
      active peptides into design of new peptides with tailored actions, as
      transporters of cargo or as antibacterial substances, targeting specific
      membranes. We have previously shown that the position of the amino acid
      tryptophan in the peptide sequence of three arginine-tryptophan peptides affects
      their uptake and intracellular localization in live mammalian cells, as well as
      their ability to inhibit bacterial growth. Here, we use quartz crystal
      microbalance with dissipation monitoring to assess the induced changes caused by
      binding of the three peptides to supported model membranes composed of POPC,
      POPC/POPG, POPC/POPG/cholesterol or POPC/lactosyl PE. Our results indicate that
      the tryptophan position in the peptide sequence affects the way these peptides
      interact with the different model membranes and that the presence of cholesterol
      in particular seems to affect the membrane interaction of the peptide with an
      even distribution of tryptophans in the peptide sequence. These results give
      mechanistic insight into the function of these peptides and may aid in the design
      of membrane-active peptides with specified cellular targets and actions.

PMID- 24743918
TI  - Protective effects of kaempferol on lipopolysaccharide-induced mastitis in mice.
AB  - Kaempferol isolated from the root of Zingiberaceae plants galangal and other
      Chinese herbal medicines have been reported to have anti-inflammatory properties.
      However, the anti-inflammatory effects of kaempferol on lipopolysaccharide (LPS)
      induced mastitis are unknown and their underlying molecular mechanisms remain to
      be explored. The aim of this study was to evaluate the effects of kaempferol on
      LPS-induced mouse mastitis. The mouse model of mastitis was induced by injection
      of LPS through the duct of mammary gland. Kaempferol was injected 1 h before and
      12 h after induction of LPS intraperitoneally. The present results showed that
      kaempferol markedly reduced infiltration of neutrophilic granulocyte, activation
      of myeloperoxidase (MPO), expression of tumor necrosis factor-alpha (TNF-alpha),
      interleukin-6 (IL-6), and interleukin-1beta (IL-1beta) in a dose-dependent
      manner, which were increased in LPS-induced mouse mastitis. Furthermore,
      kaempferol suppressed the phosphorylation of nuclear factor-kappaB (NF-kappaB)
      p65 subunit and the degradation of its inhibitor IkappaBalpha. All results
      suggest that anti-inflammatory effects of kaempferol against the LPS-induced
      mastitis possibly through inhibition of the NF-kappaB signaling pathway.
      Kaempferol may be a potential therapeutic agent for mastitis.

PMID- 24743919
TI  - Galangin dampens mice lipopolysaccharide-induced acute lung injury.
AB  - Galangin, an active ingredient of Alpinia galangal, has been shown to possess
      anti-inflammatory and antioxidant activities. Inflammation and oxidative stress
      are known to play vital effect in the pathogenesis of acute lung injury (ALI). In
      this study, we determined whether galangin exerts lung protection in
      lipopolysaccharide (LPS)-induced ALI. Male BALB/c mice were randomized to receive
      galangin or vehicle intraperitoneal injection 3 h after LPS challenge. Samples
      were harvested 24 h post LPS administration. Galangin administration decreased
      biochemical parameters of oxidative stress and inflammation, and improved
      oxygenation and lung edema in a dose-dependent manner. These protective effects
      of galangin were associated with inhibition of nuclear factor (NF)-kappaB and
      upregulation of heme oxygenase (HO)-1. Galangin reduces LPS-induced ALI by
      inhibition of inflammation and oxidative stress.

PMID- 24743920
TI  - [Treatment of syncope].
AB  - The therapy of patients with syncope is oriented to the underlying
      pathophysiological mechanisms. Patients with reflex syncope require careful
      education regarding recognition of warning signs and the avoidance of trigger
      factors. Treatment with beta blockers is nowadays obsolete. Even other drugs have
      failed to show any benefit. Pacemaker therapy should only be considered if
      syncope attacks are frequent and if there is a correlation between symptoms and
      the electrocardiogram (ECG). Because autonomic failure in patients with
      orthostatic hypotension is often drug-induced, reduction of the dosage or the
      complete elimination is the treatment of choice in these patients. A higher than
      normal salt and fluid intake as well as general measures to avoid delayed venous
      backflow, e.g. elastic stockings, may also be helpful. A change in blood pressure
      medication can be decisive for therapy success, especially in elderly patients
      with arterial hypertension. Pacemaker and defibrillator therapy is the treatment
      of choice in patients with bradycardia and tachycardia arrhythmias, respectively.
      Although these measures are simple but effective, in individual cases it is still
      difficult to find clinical proof that arrhythmic disorders are the causal factors
      for the syncope. However, also in these patients cardiac pacing should be based
      on a symptom ECG correlation. The recently conducted market release of the
      injectable miniaturized ECG recorder will alleviate the diagnostic process. The
      limits of this approach, however, become obvious when there is the suspicion of a
      life-threatening rhythm disorder, because the only difference between syncope and
      sudden cardiac death is that in one case the patient wakes up again. 

PMID- 24743921
TI  - Clinical evaluation and risk stratification in patients with syncope.
AB  - Syncope accounts for approximately 1 % of visits to emergency departments. The
      first diagnostic step is to rule out nonsyncopal conditions as a cause of the
      transient loss of consciousness. Next, the basic clinical evaluation should
      identify patients at high risk for potentially life-threatening events. These
      patients should be admitted and monitored until a diagnosis is made and
      definitive treatment can be offered. Guided by the basic evaluation findings,
      specific tests should be performed to prove or rule out the suspected diagnosis.
      In low-risk patients, this should preferably be done in an outpatient setting. To
      date, there is no consensus on a structured algorithm for the evaluation of
      patients with syncope. Therefore, it seems beneficial to formulate an algorithm
      based on the current guidelines for the management of syncope for use in the
      clinical setting. 

PMID- 24743923
TI  - In vivo ligands of MDA5 and RIG-I in measles virus-infected cells.
AB  - RIG-I-like receptors (RLRs: RIG-I, MDA5 and LGP2) play a major role in the innate
      immune response against viral infections and detect patterns on viral RNA
      molecules that are typically absent from host RNA. Upon RNA binding, RLRs trigger
      a complex downstream signaling cascade resulting in the expression of type I
      interferons and proinflammatory cytokines. In the past decade extensive efforts
      were made to elucidate the nature of putative RLR ligands. In vitro and
      transfection studies identified 5'-triphosphate containing blunt-ended double
      strand RNAs as potent RIG-I inducers and these findings were confirmed by next
      generation sequencing of RIG-I associated RNAs from virus-infected cells. The
      nature of RNA ligands of MDA5 is less clear. Several studies suggest that double
      stranded RNAs are the preferred agonists for the protein. However, the exact
      nature of physiological MDA5 ligands from virus-infected cells needs to be
      elucidated. In this work, we combine a crosslinking technique with next
      generation sequencing in order to shed light on MDA5-associated RNAs from human
      cells infected with measles virus. Our findings suggest that RIG-I and MDA5
      associate with AU-rich RNA species originating from the mRNA of the measles virus
      L gene. Corresponding sequences are poorer activators of ATP-hydrolysis by MDA5
      in vitro, suggesting that they result in more stable MDA5 filaments. These data
      provide a possible model of how AU-rich sequences could activate type I
      interferon signaling. 

PMID- 24743924
TI  - Neurotrophic corneal ulceration after retinal detachment surgery with retinectomy
      and endolaser: a case series.
AB  - IMPORTANCE: Trigeminal nerve lesions at differing levels can result in complete
      or partial corneal anesthesia and ensuing epithelial breakdown. Disease
      progression can lead to corneal ulceration, melt, and perforation. To our
      knowledge, neurotrophic corneal ulceration has not previously been reported after
      retinal detachment surgery and argon endolaser. OBSERVATION: Herein, we report a
      series of 5 cases of patients without diabetes who developed neuropathic corneal
      ulceration presumed secondary to long ciliary nerve compromise. This occurred
      within 5 to 10 weeks following vitrectomy surgery with endolaser and silicone oil
      tamponade for retinal detachment. CONCLUSIONS AND RELEVANCE: Clinicians should be
      mindful of the long ciliary nerves intraoperatively and, where possible, avoid
      heavy confluent treatment at these sites without compromising the need for
      adequate retinopexy. Where corneal anesthesia occurs, it is important to
      recognize this early and treat promptly to minimize the risk for ulceration and
      visual loss.

PMID- 24743925
TI  - The role of capillary transit time heterogeneity in myocardial oxygenation and
      ischemic heart disease.
AB  - Ischemic heart disease (IHD) is characterized by an imbalance between oxygen
      supply and demand, most frequently caused by coronary artery disease (CAD) that
      reduces myocardial perfusion. In some patients, IHD is ascribed to microvascular
      dysfunction (MVD): microcirculatory disturbances that reduce myocardial perfusion
      at the level of myocardial pre-arterioles and arterioles. In a minority of cases,
      chest pain and reductions in myocardial flow reserve may even occur in patients
      without any other demonstrable systemic or cardiac disease. In this topical
      review, we address whether these findings might be caused by impaired myocardial
      oxygen extraction, caused by capillary flow disturbances further downstream.
      Myocardial blood flow (MBF) increases approximately linearly with oxygen
      utilization, but efficient oxygen extraction at high MBF values is known to
      depend on the parallel reduction of capillary transit time heterogeneity (CTH).
      Consequently, changes in capillary wall morphology or blood viscosity may impair
      myocardial oxygen extraction by preventing capillary flow homogenization. Indeed,
      a recent re-analysis of oxygen transport in tissue shows that elevated CTH can
      reduce tissue oxygenation by causing a functional shunt of oxygenated blood
      through the tissue. We review the combined effects of MBF, CTH, and tissue oxygen
      tension on myocardial oxygen supply. We show that as CTH increases, normal
      vasodilator responses must be attenuated in order to reduce the degree of
      functional shunting and improve blood-tissue oxygen concentration gradients to
      allow sufficient myocardial oxygenation. Theoretically, CTH can reach levels such
      that increased metabolic demands cannot be met, resulting in tissue hypoxia and
      angina in the absence of flow-limiting CAD or MVD. We discuss these predictions
      in the context of MVD, myocardial infarction, and reperfusion injury. 

PMID- 24743926
TI  - The effects of parental illness and other ill family members on the adjustment of
      children.
AB  - BACKGROUND: This study addresses limitations of prior research that have used
      group comparison designs to test the effects of parental illness on youth.
      PURPOSE: This study examined differences in adjustment between children of a
      parent with illness and peers from 'healthy' families controlling for the effects
      of whether a parent or non-parent family member is ill, illness type,
      demographics and caregiving. METHODS: Based on questionnaire data, groups were
      derived from a community sample of 2,474 youth ('healthy' family, n = 1768;
      parental illness, n = 336; other family member illness, n = 254; both parental
      and other family illness, n = 116). RESULTS: The presence of any family member
      with an illness is associated with greater risk of mental health difficulties for
      youth relative to peers from healthy families. This risk is elevated if the ill
      family member is a parent and has mental illness or substance misuse.
      CONCLUSIONS: Serious health problems within a household adversely impact youth
      adjustment.

PMID- 24743927
TI  - Effects of low-volume high-intensity interval training (HIT) on fitness in
      adults: a meta-analysis of controlled and non-controlled trials.
AB  - BACKGROUND: Low-volume high-intensity interval training (HIT) appears to be an
      efficient and practical way to develop physical fitness. OBJECTIVE: Our objective
      was to estimate meta-analysed mean effects of HIT on aerobic power (maximum
      oxygen consumption [VO(2max)] in an incremental test) and sprint fitness (peak
      and mean power in a 30-s Wingate test). DATA SOURCES: Five databases (PubMed,
      MEDLINE, Scopus, BIOSIS and Web of Science) were searched for original research
      articles published up to January 2014. Search terms included 'high intensity',
      'HIT', 'sprint', 'fitness' and 'VO(2max)'. STUDY SELECTION: Inclusion criteria
      were fitness assessed pre- and post-training; training period >=2 weeks;
      repetition duration 30-60 s; work/rest ratio <1.0; exercise intensity described
      as maximal or near maximal; adult subjects aged >18 years. DATA EXTRACTION: The
      final data set consisted of 55 estimates from 32 trials for VO(2max), 23
      estimates from 16 trials for peak sprint power, and 19 estimates from 12 trials
      for mean sprint power. Effects on fitness were analysed as percentages via log
      transformation. Standard errors calculated from exact p values (where reported)
      or imputed from errors of measurement provided appropriate weightings. Fixed
      effects in the meta-regression model included type of study (controlled,
      uncontrolled), subject characteristics (sex, training status, baseline fitness)
      and training parameters (number of training sessions, repetition duration,
      work/rest ratio). Probabilistic magnitude-based inferences for meta-analysed
      effects were based on standardized thresholds for small, moderate and large
      changes (0.2, 0.6 and 1.2, respectively) derived from between-subject standard
      deviations (SDs) for baseline fitness. RESULTS: A mean low-volume HIT protocol
      (13 training sessions, 0.16 work/rest ratio) in a controlled trial produced a
      likely moderate improvement in the VO(2max) of active non-athletic males (6.2 %;
      90 % confidence limits +/-3.1 %), when compared with control. There were possibly
      moderate improvements in the VO(2max) of sedentary males (10.0 %; +/-5.1 %) and
      active non-athletic females (3.6 %; +/-4.3 %) and a likely small increase for
      sedentary females (7.3 %; +/-4.8 %). The effect on the VO(2max) of athletic males
      was unclear (2.7 %; +/-4.6 %). A possibly moderate additional increase was likely
      for subjects with a 10 mL.kg(-1).min(-1) lower baseline VO(2max) (3.8 %; +/-2.5
      %), whereas the modifying effects of sex and difference in exercise dose were
      unclear. The comparison of HIT with traditional endurance training was unclear (
      1.6 %; +/-4.3 %). Unexplained variation between studies was 2.0 % (SD). Meta
      analysed effects of HIT on Wingate peak and mean power were unclear. CONCLUSIONS:
      Low-volume HIT produces moderate improvements in the aerobic power of active non
      athletic and sedentary subjects. More studies are needed to resolve the unclear
      modifying effects of sex and HIT dose on aerobic power and the unclear effects on
      sprint fitness.

PMID- 24743928
TI  - Acute exercise and hormones related appetite regulation: comparison of meta
      analytical methods.

PMID- 24743929
TI  - A review of adolescent high-intensity interval training.
AB  - Despite the promising evidence supporting positive effects of high-intensity
      interval training (HIIT) on the metabolic profile in adults, there is limited
      research targeting adolescents. Given the rising burden of chronic disease, it is
      essential to implement strategies to improve the cardiometabolic health in
      adolescence, as this is a key stage in the development of healthy lifestyle
      behaviours. This narrative review summarises evidence of the relative efficacy of
      HIIT regarding the metabolic health of adolescents. Methodological
      inconsistencies confound our ability to draw conclusions; however, there is
      meaningful evidence supporting HIIT as a potentially efficacious exercise
      modality for use in the adolescent cohort. Future research must examine the
      effects of various HIIT protocols to determine the optimum strategy to deliver
      cardiometabolic health benefits. Researchers should explicitly show between-group
      differences for HIIT intervention and steady-state exercise or control groups, as
      the magnitude of difference between HIIT and other exercise modalities is of key
      interest to public health. There is scope for research to examine the
      palatability of HIIT as an exercise modality for adolescents through
      investigating perceived enjoyment during and after HIIT, and consequent long-term
      exercise adherence. 

PMID- 24743930
TI  - The forgotten pieces of the high-intensity interval training puzzle.

PMID- 24743931
TI  - Physical activity in overweight and obese adolescents: systematic review of the
      effects on physical fitness components and cardiovascular risk factors.
AB  - BACKGROUND: The increasing prevalence of obesity in the pediatric age range has
      become a major concern. Studies have investigated the role of physical activity
      (PA) to prevent obesity in this population. However, previous reviews did not
      focus on the effects of PA in overweight/obese adolescents on physical fitness
      and risk factors for cardiovascular disease altogether. OBJECTIVE: The present
      systematic review analyzed trials investigating the effect of PA on aerobic
      capacity, muscle strength, body composition, hemodynamic variables, biochemical
      markers, and endothelial function in obese/overweight adolescents. METHODS:
      PubMed, LILACS, Web of Science, Scopus (including Embase), and SPORTDiscus
      databases were searched for relevant reports without time limits. Inclusion
      criteria included studies published in English, with overweight and obese
      adolescents aged 12-17 years. The review was registered (Number CRD42013004632)
      on PROSPERO, the International Prospective Register of Systematic Reviews.
      RESULTS: The results indicated that PA is associated with significant and
      beneficial changes in fat percentage, waist circumference, systolic blood
      pressure, insulin, low-density lipoprotein cholesterol, and total cholesterol, as
      well as with small non-significant changes in diastolic blood pressure, glucose,
      and high-density lipoprotein cholesterol. CONCLUSION: Although limited, results
      from controlled trials suggest that PA intervention may improve physical fitness
      and risk factors for cardiovascular disease in adolescents who are overweight or
      obese.

PMID- 24743932
TI  - Pharmacological and structure-activity relationship evaluation of 4-aryl-1
      diphenylacetyl(thio)semicarbazides.
AB  - This article describes the synthesis of six 4-aryl-(thio)semicarbazides (series a
      and b) linked with diphenylacetyl moiety along with their pharmacological
      evaluation on the central nervous system in mice and computational studies,
      including conformational analysis and electrostatic properties. All
      thiosemicarbazides (series b) were found to exhibit strong antinociceptive
      activity in the behavioural model. Among them, compound 1-diphenylacetyl-4-(4
      methylphenyl)thiosemicarbazide 1b was found to be the most potent analgesic
      agent, whose activity is connected with the opioid system. For compounds from
      series a significant anti-serotonergic effect, especially for compound 1
      diphenylacetyl-4-(4-methoxyphenyl)semicarbazide 2b was observed. The
      computational studies strongly support the obtained results. 

PMID- 24743933
TI  - Spectroscopic and molecular docking studies of the in vitro interaction between
      puerarin and cytochrome P450.
AB  - Puerarin, an isoflavone glycoside extracted from Pueraria plants, has various
      medical functions. Cytochrome P450s (CYPs) are crucial phase I metabolizing
      enzymes, which have been spotlighted for their effects on drug metabolism. The
      interaction between puerarin and CYPs (CYP1A2 and CYP2D6) was investigated by
      fluorescence, UV-Vis and circular dichroism spectroscopies, as well as molecular
      docking, to explore the underlying mechanism under simulated physiological
      conditions. The molecular docking results indicated that puerarin interacted with
      CYPs mainly by hydrophobic force and hydrogen bonding. The fluorescences of CYPs
      were quenched statically. Binding constants (Ka) and number of binding sites (n)
      at different temperatures were calculated, with the results being consistent with
      those of molecular docking. At the same temperature, puerarin bound to CYP1A2
      more weakly than it did to CYP2D6. UV-Vis and circular dichroism spectroscopies
      confirmed the micro-environmental and conformational changes of CYP1A2 and
      CYP2D6. The findings provide reliable evidence for clarifying the structures and
      functions of CYPs. 

PMID- 24743934
TI  - Granulocyte colony-stimulating factor in the treatment of acute radiation
      syndrome: a concise review.
AB  - This article concisely summarizes data on the action of one of the principal and
      best known growth factors, the granulocyte colony-stimulating factor (G-CSF), in
      a mammalian organism exposed to radiation doses inducing acute radiation
      syndrome. Highlighted are the topics of its real or anticipated use in radiation
      accident victims, the timing of its administration, the possibilities of
      combining G-CSF with other drugs, the ability of other agents to stimulate
      endogenous G-CSF production, as well as of the capability of this growth factor
      to ameliorate not only the bone marrow radiation syndrome but also the
      gastrointestinal radiation syndrome. G-CSF is one of the pivotal drugs in the
      treatment of radiation accident victims and its employment in this indication can
      be expected to remain or even grow in the future. 

PMID- 24743935
TI  - Optimization of fermentation conditions for the production of the M23 protease
      Pseudoalterin by deep-sea Pseudoalteromonas sp. CF6-2 with artery powder as an
      inducer.
AB  - Proteases in the M23 family have specific activities toward elastin and bacterial
      peptidoglycan. The peptidoglycan-degrading property makes these proteases have
      potential as novel antimicrobials. Because M23 proteases cannot be maturely
      expressed in Escherichia coli, it is significant to improve the production of
      these enzymes in their wild strains. Pseudoalterin is a new M23 protease secreted
      by the deep-sea bacterium Pseudoalteromonas sp. CF6-2. In this study, the
      fermentation conditions of strain CF6-2 for pseudoalterin production were
      optimized using single factor experiments and response surface methodology to
      improve the enzyme yield. To reduce the fermentation cost, bovine artery powder
      instead of elastin was determined as a cheap and efficient inducer. Based on
      single factor experiments, artery powder content, culture temperature and culture
      time were determined as the main factors influencing pseudoalterin production and
      were further optimized by the central composite design. The optimal values of
      these factors were determined as: artery powder of 1.2%, culture temperature of
      20.17  degrees C and culture time of 28.04 h. Under the optimized conditions,
      pseudoalterin production reached 100.02+/-9.0 U/mL, more than twice of that
      before optimization. These results lay a good foundation for developing the
      biotechnological potential of pseudoalterin.

PMID- 24743936
TI  - Synthesis and anti-hypertensive effects of the twin drug of nicotinic acid and
      quercetin tetramethyl ether.
AB  - A novel twin drug consisting of nicotinic acid (VB3) and quercetin tetramethyl
      ether (QTME) has been synthesized as an antihypertensive in a total yield of
      79.2% through methylation, hydrolysis, acylation and esterification starting from
      rutin. The structures of synthesized compounds were elucidated by 1H-NMR, 13C-NMR
      and elemental analysis. The anti-hypertensive effects of an oral daily dose (15
      mg/kg) of the synthesized compounds in spontaneously hypertensive (SHR) rats and
      normotensive Wistar Kyoto (WKY) rats were analysed. The data demonstrate that the
      twin drug VB3-QTME both reduces the elevated blood pressure and prolongs the
      action time in SHR rats without effect on WKY rats. However, definitive evidence
      of a precise mechanism of action by which VB3-QTME might decrease blood pressure
      remains elusive. Based on the results, the therapeutic potential of this twin
      drug is discussed. 

PMID- 24743937
TI  - Three new triterpene esters from pumpkin (Cucurbita maxima) seeds.
AB  - Three new multiflorane-type triterpene esters, i.e. 7alpha-hydroxymultiflor-8-ene
      3alpha,29-diol 3-acetate-29-benzoate (1), 7alpha-methoxymultiflor-8-ene-3alpha,29
      diol 3,29-dibenzoate (2), and 7beta-methoxymultiflor-8-ene-3alpha,29-diol 3,29
      dibenzoate (3), were isolated from seeds of Cucurbita maxima, along with the
      known compound, multiflora-7,9(11)-diene-3alpha,29-diol 3,29-dibenzoate (4).
      Compound 1 exhibited melanogenesis inhibitory activities comparable with those of
      arbutin. In cytotoxicity assays, compounds 1 and 3 exhibited weak cytotoxicity,
      with IC50 values of 34.5-93.7 MUM against HL-60 and P388 cells. 

PMID- 24743938
TI  - Exploring the Phe-Gly dipeptide-derived piperazinone scaffold in the search for
      antagonists of the thrombin receptor PAR1.
AB  - A series of Phe-Gly dipeptide-derived piperazinones containing an aromatic urea
      moiety and a basic amino acid has been synthesized and evaluated as inhibitors of
      human platelet aggregation induced by the PAR1 agonist SFLLRN and as cytotoxic
      agents in human cancer cells. The synthetic strategy involves coupling of a
      protected basic amino acid benzyl amide to 1,2- and 1,2,4-substituted
      piperazinone derivatives, through a carbonylmethyl group at the N1-position,
      followed by formation of an aromatic urea at the exocyclic moiety linked at the
      C2 position of the piperazine ring and removal of protecting groups. None of the
      compounds showed activity in the biological evaluation. 

PMID- 24743939
TI  - A crucial role of N-terminal domain of influenza A virus M1 protein in
      interaction with swine importin alpha1 protein.
AB  - The matrix 1 (M1) protein is a multifunctional protein in the life cycle of
      influenza virus. It plays an important role in virus budding and intracellular
      trafficking of viral ribonucleoproteins (vRNPs). The M1 protein consists of three
      domains based on the structure: N-terminal domain, Middle domain, and C-terminal
      domain. However, the functions of different domains of the M1 protein remain
      largely unclear. In this study, using bimolecular fluorescence complementation
      assays (BIFC) we demonstrated that swine importin alpha1 interacts with the M1
      protein and transports it to the nucleus. Interestingly, M1 with mutated nuclear
      localization signal (NLS; 101-RKLKR-105 to 101-AALAA-105) still interacts with
      swine importin alpha1 and is localized in the nucleus, suggesting that the NLS
      located at residues 101-105 is not the only NLS within M1 recombinant protein
      containing 1-160 residues of M1 with mutated nuclear localization signal is able
      to interact with swine importin alpha1, but M1/60-252 domains cannot bind
      importin alpha1. Further mapping showed that the deletion of residues 1-20
      impaired the interaction between N terminus of M1 and importin alpha1.
      Collectively, our data suggested that the N-terminal domain of M1 protein is
      critical for binding swine importin alpha1 and for nuclear localization. 

PMID- 24743940
TI  - Orf virus (ORFV) ANK-1 protein mitochondrial localization is mediated by ankyrin
      repeat motifs.
AB  - Orf virus (ORFV) strain D1701-V, a Parapoxvirus belonging to the family
      Poxviridae, became attractive as a novel virus vector system that we successfully
      used for the generation of recombinant vaccines. Therefore, the identification of
      viral genes involved in host tropisms or immune modulation is of great interest,
      as for instance the ORFV-encoded ankyrin-repeat (AR) containing proteins. The
      present study shows for the first time that the ANK-1 designated gene product of
      ORFV126 is targeted to mitochondria of ORFV-infected and in ANK-1 transiently
      expressing cells. Taking advantage of ANK-1 EGFP fusion proteins and confocal
      fluorescence microscopy mutational and deletion analyses indicated the importance
      of AR8 and AR9, which may contain a novel class of mitochondria-targeting
      sequence (MTS) in the central to C-terminal part of this AR-containing protein.
      The fluorescent findings were corroborated by cell fractionation and Western
      blotting experiments. The presented results open the avenue for more detailed
      investigations on cellular binding partners and the function of ANK-1 in viral
      replication or virulence.

PMID- 24743941
TI  - Diabetes and depression.
AB  - Diabetes and depression occur together approximately twice as frequently as would
      be predicted by chance alone. Comorbid diabetes and depression are a major
      clinical challenge as the outcomes of both conditions are worsened by the other.
      Although the psychological burden of diabetes may contribute to depression, this
      explanation does not fully explain the relationship between these 2 conditions.
      Both conditions may be driven by shared underlying biological and behavioral
      mechanisms, such as hypothalamic-pituitary-adrenal axis activation, inflammation,
      sleep disturbance, inactive lifestyle, poor dietary habits, and environmental and
      cultural risk factors. Depression is frequently missed in people with diabetes
      despite effective screening tools being available. Both psychological
      interventions and antidepressants are effective in treating depressive symptoms
      in people with diabetes but have mixed effects on glycemic control. Clear care
      pathways involving a multidisciplinary team are needed to obtain optimal medical
      and psychiatric outcomes for people with comorbid diabetes and depression. 

PMID- 24743942
TI  - Cardiovascular risk stratification and management in pre-diabetes.
AB  - Prediabetes, covering individuals with impaired fasting glycemia, impaired
      glucose tolerance, or high-risk HbA1c levels, is associated with a ~20 %
      increased risk of developing cardiovascular disease (CVD) compared with
      normoglycemic individuals. It is well-known that lifestyle or pharmacologic
      interventions can prevent diabetes in prediabetic people; however, the evidence
      is less clear regarding prevention of CVD. Most diabetes prevention trials have
      failed to show beneficial effects on CVD morbidity and mortality despite
      significant improvements of CVD risk factors in individuals with prediabetes.
      Another challenge is how to estimate CVD risk in prediabetic people. In general,
      prediction models for CVD do not take glucose levels or prediabetes status into
      account, thereby underestimating CVD risk in these high-risk individuals. More
      evidence within risk stratification and management of CVD risk in prediabetes is
      needed in order to recommend useful and effective strategies for early prevention
      of CVD.

PMID- 24743944
TI  - Spectrum of congenital defects of the eye and its adnexia in the pediatric age
      group; experience at a tertiary facility in Nigeria.
AB  - The aim of this study was to investigate the types and presentation pattern of
      congenital defects of the eye and adnexia in our center. This is a retrospective
      review of congenital defects of the eye and adnexia over a 20-month period at a
      tertiary referral center in Lagos, Nigeria. Records were analyzed for age at
      presentation, laterality, gender, vision assessment, and type(s) of abnormality.
      Out of 412 pediatric patients, 40 (9.7 %) were seen to have congenital
      abnormality of the eye and/or its adnexia during the study period. There were 17
      (42.5 %) males. Twelve patients (30.0 %) presented with involvement of the right
      eyes, nine (22.5 %) with left eyes, while 19 (47.5 %) had bilateral involvement.
      Twenty-eight patients (70.0 %) were aged 1 year or less at the time of
      presentation. A total of 69 entities were recognized as some children had two or
      more malformations. The common congenital defects identified were cataract (39.1
      %), ptosis (17.4 %), glaucoma (8.7 %), and cornea opacity (7.2 %). Other less
      common congenital defects include: microphthalmos, anophthalmos, coloboma (lid
      and iris), dermoid cyst, and aniridia. All of the patients with available visual
      acuity documentation had visual impairment. A high proportion of the patients
      were lost to follow-up. Cataract, ptosis, and glaucoma were the commonest
      congenital defects of the eye and adnexia in our center and were associated with
      visual impairments. The significant loss of the patients during follow-up needs
      urgent investigation and attention to forestall this trend.

PMID- 24743943
TI  - [Pilot study of levosimendan : Effect on liver blood flow and liver function in
      acute decompensated heart failure].
AB  - BACKGROUND: In a pilot study, 9 patients (39-48 years) with acute decompensated
      heart failure and a cardiac index (CI) of 1.9 +/- 0.3 l/min/m(2) were included
      after exclusion of an underlying hepatic disease. MATERIALS AND METHODS: The
      effect of levosimendan on liver blood flow and liver function was measured with
      the LiMON((r)) system using the indocyane green plasma disappearance rate (ICG
      PDR). RESULTS: Levosimendan (Simdax((r))) infusion resulted in a significant
      increase of the CI, thus, achieving normal ranges of 2.9 +/- 0.9 l/min/m(2) after
      4 h and 3.3 +/- 1 l/min/m(2) (p = 0.003) after 24 h. ICG PDR increased from 8.2
      +/- 0.8 % to 10.2 + 1.8 % after 4 h and to 11.9 +/- 2.9 % after 24 h (p = 0.04).
      DISCUSSION: The reason for the early increase in systemic blood flow with no
      concomitant change in ICG PDR is not clear. A primary increase in liver blood
      flow with sustained low liver function might be one explanation; a low flow
      mediated increased release of cytokines from liver cells with consequent
      deterioration of liver function is another possible explanation.

PMID- 24743945
TI  - MiR-142-3p attenuates the migration of CD4+ T cells through regulating actin
      cytoskeleton via RAC1 and ROCK2 in arteriosclerosis obliterans.
AB  - The migration of CD4+ T cells plays an important role in arteriosclerosis
      obliterans (ASO). However, the molecular mechanisms involved in CD4+ T cell
      migration are still unclear. The current study is aimed to determine the
      expression change of miR-142-3p in CD4+ T cells from patients with ASO and
      investigate its role in CD4+ T cell migration as well the potential mechanisms
      involved. We identified by qRT-PCR and in situ hybridization that the expression
      of miR-142-3p in CD4+ T cells was significantly down-regulated in patients with
      ASO. Chemokine (C-X-C motif) ligand 12 (CXCL12), a common inflammatory chemokine
      under the ASO condition, was able to down-regulate the expression of miR-142-3p
      in cultured CD4+ T cells. Up-regulation of miR-142-3p by lentivirus-mediated gene
      transfer had a strong inhibitory effect on CD4+ T cell migration both in cultured
      human cells in vitro and in mouse aortas and spleens in vivo. RAC1 and ROCK2 were
      identified to be the direct target genes in human CD4+ T cells, which are further
      confirmed by dual luciferase assay. MiR-142-3p had strong regulatory effects on
      actin cytoskeleton as shown by the actin staining in CD4+ T cells. The results
      suggest that the expression of miR-142-3p is down-regulated in CD4+ T cells from
      patients with ASO. The down-regulation of miR-142-3p could increase the migration
      of CD4+ T cells to the vascular walls by regulation of actin cytoskeleton via its
      target genes, RAC1 and ROCK2.

PMID- 24743947
TI  - A presentation of invasive squamous cell carcinoma (white cornea).

PMID- 24743946
TI  - Genetic variation in the major histocompatibility complex of the European brown
      hare (Lepus europaeus) across distinct phylogeographic areas.
AB  - The major histocompatibility complex is one of the best studied systems in
      vertebrates providing evidence for the long-term action of selection. Here, we
      examined the intra- and inter-population genetic diversity of the MHC class II
      DRB locus in European brown hare (Lepus europaeus) and correlated the results
      with genetic variability already estimated from the MHC DQA locus and from
      maternally (mitochondrial DNA (mtDNA)) and biparentally (allozymes,
      microsatellites) inherited loci. L. europaeus showed remarkable genetic
      polymorphism in both DQA and DRB1 loci. The Anatolian populations exhibited the
      highest genetic polymorphism for both loci. Balancing selection has established
      increased variability in the European populations despite the founder effects
      after the last glaciation. Different evolutionary rates were traced for DRB1 and
      DQA loci, as evidenced by the higher number of common DRB1 than DQA alleles and
      the greater differences between DRB1 alleles with common origin in comparison
      with DQA alleles. The high number of rare alleles with low frequencies detected
      implies that frequency-dependent selection drives MHC evolution in the brown hare
      through the advantage of rare alleles. Both loci were under the influence of
      positive selection within the peptide-binding region. The functional
      polymorphism, recorded as amino acid substitutions within the binding pockets,
      fell also within distinct geographic patterns, yet it was much narrower than the
      genetic polymorphism. We hypothesize that certain structural and functional
      characteristics of the binding pockets set limitations to the actual shape of
      genetic polymorphism in MHC. 

PMID- 24743948
TI  - Anthocyans as tertiary chemopreventive agents in bladder cancer: anti-oxidant
      mechanisms and interaction with mitomycin C.
AB  - Bladder cancer is associated with high rates of recurrence making tertiary
      chemoprevention an attractive intervention strategy. Anthocyanins have been shown
      to possess chemopreventive properties and are detectable in urine after oral
      ingestion, with higher concentrations achievable via intravesical administration
      alongside current chemotherapeutic regimens. Yet their apparent ability to
      protect against certain DNA damage may in turn interfere with cancer treatments.
      Our aim was therefore to determine the potential of anthocyanins as
      chemopreventive agents in bladder cancer, their mode of action and effects, both
      alone and in combination with mitomycin C (MMC). In this study we showed that
      mirtoselect, a standardised mixture of anthocyanins, possesses significant anti
      proliferative activity, causing growth inhibition and apoptosis in bladder cancer
      cell lines. The anti-oxidative potential of mirtoselect was examined and revealed
      significantly fewer H2O2-induced DNA strand breaks, as well as oxidised DNA bases
      in pre-treated cells. In contrast, endogenous levels of oxidised DNA bases were
      unaltered. Investigations into the possible protective mechanisms associated with
      these anti-oxidant properties revealed that mirtoselect chelates metal ions. In
      mirtoselect/MMC combination studies, no adverse effects on measures of DNA damage
      were observed compared to treatment with MMC alone and there was evidence of
      enhanced cell death. Consistent with this, significantly more DNA crosslinks were
      formed in cells treated with the combination. These results show that mirtoselect
      exerts effects consistent with chemopreventive properties in bladder cancer cell
      lines and most importantly does so without adversely affecting the effects of
      drugs used in current treatment regimens. We also provide evidence that
      mirtoselect's anti-oxidative mechanism of action is via metal ion chelation.
      Overall these results suggest that mirtoselect could be an effective
      chemopreventive agent in bladder cancer and provides the necessary pre-clinical
      data for future in vivo animal studies and clinical trials. 

PMID- 24743950
TI  - Global malaria efforts: progress made, but challenges loom ahead.

PMID- 24743949
TI  - Deficient IFN signaling by myeloid cells leads to MAVS-dependent virus-induced
      sepsis.
AB  - The type I interferon (IFN) signaling response limits infection of many RNA and
      DNA viruses. To define key cell types that require type I IFN signaling to
      orchestrate immunity against West Nile virus (WNV), we infected mice with
      conditional deletions of the type I IFN receptor (IFNAR) gene. Deletion of the
      Ifnar gene in subsets of myeloid cells resulted in uncontrolled WNV replication,
      vasoactive cytokine production, sepsis, organ damage, and death that were
      remarkably similar to infection of Ifnar-/- mice completely lacking type I IFN
      signaling. In Mavs-/-*Ifnar-/- myeloid cells and mice lacking both Ifnar and the
      RIG-I-like receptor adaptor gene Mavs, cytokine production was muted despite high
      levels of WNV infection. Thus, in myeloid cells, viral infection triggers
      signaling through MAVS to induce proinflammatory cytokines that can result in
      sepsis and organ damage. Viral pathogenesis was caused in part by massive
      complement activation, as liver damage was minimized in animals lacking
      complement components C3 or factor B or treated with neutralizing anti-C5
      antibodies. Disease in Ifnar-/- and CD11c Cre+Ifnarf/f mice also was facilitated
      by the proinflammatory cytokine TNF-alpha, as blocking antibodies diminished
      complement activation and prolonged survival without altering viral burden.
      Collectively, our findings establish the dominant role of type I IFN signaling in
      myeloid cells in restricting virus infection and controlling pathological
      inflammation and tissue injury. 

PMID- 24743951
TI  - Yellow fever, Asia and the East African slave trade.
AB  - Yellow fever is endemic in parts of sub-Saharan Africa and South America, yet its
      principal vectors--species of mosquito of the genus Aedes--are found throughout
      tropical and subtropical latitudes. Phylogenetic analyses indicate that yellow
      fever originated in Africa and that its spread to the New World coincided with
      the slave trade, but why yellow fever has never appeared in Asia remains a
      mystery. None of several previously proposed explanations for its absence there
      is considered satisfactory. We contrast the trans-Atlantic slave trade, and trade
      across the Sahara and to the Arabian Peninsula and Mesopotamia, with that to Far
      East and Southeast Asian ports before abolition of the African slave trade, and
      before the scientific community understood the transmission vector of yellow
      fever and the viral life cycle, and the need for shipboard mosquito control. We
      propose that these differences in slave trading had a primary role in the
      avoidance of yellow fever transmission into Asia in the centuries before the
      20(th) century. The relatively small volume of the Black African slave trade
      between Africa and East and Southeast Asia has heretofore been largely ignored.
      Although focal epidemics may have occurred, the volume was insufficient to reach
      the threshold for endemicity.

PMID- 24743953
TI  - Assessing resident performance on the psychiatry milestones.

PMID- 24743954
TI  - Enhanced mucosal imaging and the esophagus--ready for prime time?
AB  - Innovation of endoscopic technology has recently been introduced to improve real
      time visualization of mucosal architecture and subepithelial vascular structures.
      Since the esophagus is easily accessible using endoscopy and the length of
      required observation is limited, many different types of new imaging modalities
      have been reported and showing promising data. Early detection of neoplastic
      changes in the esophagus is devoted to the treatment in early stage cancer and
      theoretically leads to better prognosis. This review will focus on the emerging
      endoscopic technologies for the management of esophageal cancer. 

PMID- 24743955
TI  - New therapies for non-cardiac chest pain.
AB  - After excluding a cardiac cause, potent anti-reflux therapy should be
      administered to patients with non-cardiac chest pain since gastroesophageal
      reflux disease (GERD) is the most common underlying mechanism of this disorder.
      If GERD is an unlikely cause of patient's symptoms, an esophageal motor disorder
      should be excluded. Spastic motility disorders can be treated with a smooth
      muscle relaxant (such as calcium channel blocker, nitrate, or phosphodiesterase 5
      inhibitors). Alternatively, spastic motility disorders may respond to anti
      spasmodics, pain modulators, botulinum toxin injection into the distal esophagus,
      and/or surgery. Patients with functional chest pain have recently seen an
      expanded treatment armamentarium including medications such as trazadone,
      tricyclic anti-depressants, selective serotonin reuptake inhibitors, serotonin
      norepinephrine reuptake inhibitors, pregabalin, and/or ramelteon. 

PMID- 24743956
TI  - Which coastal and marine environmental contaminants are truly emerging?
AB  - To better understand the past and present impact of contaminants of emerging
      concern (CECs) in coastal and marine ecosystems, archived samples were analyzed
      for a broad suite of analytes, including pharmaceuticals and personal care
      products (PPCPs), flame retardants (including PBDEs), perfluorinated compounds
      (PFCs), and current-use pesticides. Surface sediment, mussels (Mytilus spp.) and
      sediment core samples collected from the California (USA) coast were obtained
      from environmental specimen banks. Selected CECs were detected in recent surface
      sediments, with nonylphenol (4-NP), its mono- and di-ethoxylates (NP1EO and
      NP2EO), triclocarban, and pyrethroid insecticides in the greatest abundance.
      Alkylphenols, triclocarban, and triclosan were present in sediment core segments
      from the 1970s, as well as in Mytilus tissue collected during the 1990s.
      Increasing concentrations of some CECs (e.g., miconazole, triclosan) were
      observed in the surface layers (ca. 2007) of a sediment core, in contrast to peak
      concentrations of 4-NP and triclocarban corresponding to input during the 1970s,
      and an apparent peak input for PBDEs during the 1990s. These results suggest that
      chemicals sometimes referred to as "emerging" (e.g., alkylphenols, triclocarban)
      have been present in the aquatic environment for several decades and are
      decreasing in concentration, whereas others (e.g., miconazole, triclosan) are
      increasing. 

PMID- 24743957
TI  - Comparison of carbon balance in Mediterranean pilot constructed wetlands
      vegetated with different C4 plant species.
AB  - This study investigates carbon dioxide (CO2) and methane (CH4) emissions and
      carbon (C) budgets in a horizontal subsurface flow pilot-plant constructed
      wetland (CW) with beds vegetated with Cyperus papyrus L., Chrysopogon zizanioides
      (L.) Roberty, and Mischantus * giganteus Greef et Deu in the Mediterranean basin
      (Sicily) during the 1st year of plant growing season. At the end of the
      vegetative season, M. giganteus showed the higher biomass accumulation (7.4 kg m(
      2)) followed by C. zizanioides (5.3 kg m(-2)) and C. papyrus (1.8 kg m(-2)).
      Significantly higher emissions of CO2 were detected in the summer, while CH4
      emissions were maximum during spring. Cumulative CO2 emissions by C. papyrus and
      C. zizanioides during the monitoring period showed similar trends with final
      values of about 775 and 1,074 g m(-2), respectively, whereas M. giganteus emitted
      3,395 g m(-2). Cumulative CH4 bed emission showed different trends for the three
      C4 plant species in which total gas release during the study period was for C.
      papyrus 12.0 g m(-2) and ten times higher for M. giganteus, while C. zizanioides
      bed showed the greatest CH4 cumulative emission with 240.3 g m(-2). The
      wastewater organic carbon abatement determined different C flux in the
      atmosphere. Gas fluxes were influenced both by plant species and monitored months
      with an average C-emitted-to-C-removed ratio for C. zizanioides, C. papyrus, and
      M. giganteus of 0.3, 0.5, and 0.9, respectively. The growing season C balances
      were positive for all vegetated beds with the highest C sequestered in the bed
      with M. giganteus (4.26 kg m(-2)) followed by C. zizanioides (3.78 kg m(-2)) and
      C. papyrus (1.89 kg m(-2)). To our knowledge, this is the first paper that
      presents preliminary results on CO2 and CH4 emissions from CWs vegetated with C4
      plant species in Mediterranean basin during vegetative growth.

PMID- 24743958
TI  - Characterization of hydrocarbon-degrading and biosurfactant-producing Pseudomonas
      sp. P-1 strain as a potential tool for bioremediation of petroleum-contaminated
      soil.
AB  - The Pseudomonas sp. P-1 strain, isolated from heavily petroleum hydrocarbon
      contaminated soil, was investigated for its capability to degrade hydrocarbons
      and produce a biosurfactant. The strain degraded crude oil, fractions A5 and P3
      of crude oil, and hexadecane (27, 39, 27 and 13% of hydrocarbons added to culture
      medium were degraded, respectively) but had no ability to degrade phenanthrene.
      Additionally, the presence of gene-encoding enzymes responsible for the
      degradation of alkanes and naphthalene in the genome of the P-1 strain was
      reported. Positive results of blood agar and methylene blue agar tests, as well
      as the presence of gene rhl, involved in the biosynthesis of rhamnolipid,
      confirmed the ability of P-1 for synthesis of glycolipid biosurfactant. 1H and
      13C nuclear magnetic resonance, Fourier transform infrared spectrum and mass
      spectrum analyses indicated that the extracted biosurfactant was affiliated with
      rhamnolipid. The results of this study indicate that the P-1 and/or biosurfactant
      produced by this strain have the potential to be used in bioremediation of
      hydrocarbon-contaminated soils.

PMID- 24743960
TI  - Factors influencing HIV serodisclosure among men who have sex with men in the US:
      an examination of online versus offline meeting environments and risk behaviors.
AB  - One key component in HIV prevention is serostatus disclosure. Until recently,
      many studies have focused on interpersonal factors and minimally considered
      meeting venues as they pertain to disclosure. Using data (N = 3,309) from an
      online survey conducted across 16 U.S. metropolitan statistical areas, we
      examined whether HIV serodisclosure varies by online/offline meeting venues in
      both protected and unprotected anal intercourse encounters. Most of the sample
      (76.9 %) reported meeting men for sex (last 90 days) both online and offline,
      versus 12.7 % offline only and 10.4 % online only. After controlling for other
      variables, we found that the men who meet partners in both online and offline
      were 20~30 % more likely to report disclosing their HIV status prior to sex than
      men who met their partners exclusively either offline or online. While previous
      studies have identified the Internet as a risk environment, our findings suggest
      bi-environmental partner seeking may also have beneficial effects. 

PMID- 24743959
TI  - "Amar te Duele" ("love hurts"): sexual relationship power, intimate partner
      violence, depression symptoms and HIV risk among female sex workers who use drugs
      and their non-commercial, steady partners in Mexico.
AB  - A significant body of research among female sex workers (FSWs) has focused on
      individual-level HIV risk factors. Comparatively little is known about their non
      commercial, steady partners who may heavily influence their behavior and HIV
      risk. This cross-sectional study of 214 FSWs who use drugs and their male steady
      partners aged >=18 in two Mexico-U.S. border cities utilized a path-analytic
      model for dyadic data based upon the Actor-Partner Interdependence Model to
      examine relationships between sexual relationship power, intimate partner
      violence (IPV), depression symptoms, and unprotected sex. FSWs' relationship
      power, IPV perpetration and victimization were significantly associated with
      unprotected sex within the relationship. Male partners' depression symptoms were
      significantly associated with unprotected sex within the relationship. Future HIV
      prevention interventions for FSWs and their male partners should address issues
      of sexual relationship power, IPV, and mental health both individually and in the
      context of their relationship. 

PMID- 24743961
TI  - Suicidal erythrocyte death in end-stage renal disease.
AB  - Anemia in end-stage renal disease (ESRD) results mainly from erythropoietin and
      iron deficiency. Anemia could be confounded, however, by accelerated clearance of
      circulating erythrocytes because of premature suicidal erythrocyte death or
      eryptosis characterized by phosphatidylserine exposure at the erythrocyte
      surface. Triggers of eryptosis include increased cytosolic Ca(2+) concentration
      ([Ca(2+)]i), oxidative stress, and ceramide. The present study explored whether
      and how ESRD influences eryptosis. Blood was drawn from healthy volunteers (n =
      20) as well as ESRD patients (n = 20) prior to and after hemodialysis.
      Phosphatidylserine exposure was estimated from annexin V binding, [Ca(2+)]i from
      Fluo3-fluorescence, reactive oxygen species (ROS) from
      2',7'dichlorodihydrofluorescein fluorescence, and ceramide from fluorescein
      isothiocyanate-conjugated antibody binding in flow cytometry. Measurements were
      made in erythrocytes from freshly drawn blood and in erythrocytes from healthy
      volunteers exposed in vitro for 24 h to plasma from healthy volunteers or ESRD
      patients prior to and following dialysis. The patients suffered from anemia
      (hemoglobin 10.1 +/- 0.5 g/100 ml) despite 1.96 +/- 0.34 % reticulocytes. The
      percentage of phosphatidylserine-exposing erythrocytes was significantly higher
      in ESRD patients (0.84 +/- 0.09 %) than in healthy volunteers (0.43 +/- 0.04 %)
      and was significantly increased immediately after dialysis (1.35 +/- 0.13 %). The
      increase in phosphatidylserine exposure was paralleled by increase in [Ca(2+)]i,
      oxidative stress, and ceramide abundance. As compared to addition of plasma from
      healthy individuals, addition of predialytic but not of postdialytic plasma from
      ESRD patients increased phosphatidylserine exposure, [Ca(2+)]i, ROS, and ceramide
      abundance. In conclusion, both, dialyzable components of uremic plasma and
      dialysis procedure, trigger eryptosis at least in part by increasing erythrocyte
      [Ca(2+)]i, ROS, and ceramide formation. KEY MESSAGES: Anemia in uremia results in
      part from eryptosis, the suicidal erythrocyte death. Eryptosis in uremia is
      triggered in part by a dialyzable plasma component. Eryptosis in uremia is
      further triggered by dialysis procedure. Eryptosis in uremia is in part due to
      increased cytosolic Ca(2+) concentration. Eryptosis in uremia is further due to
      oxidative stress and ceramide formation.

PMID- 24743962
TI  - The identification of tuberculosis biomarkers in human urine samples.
AB  - We aimed to determine whether shotgun proteomic approaches could be used to
      identify tuberculosis (TB)-specific biomarkers in the urine of well-characterised
      patients with active TB versus no TB. Patients with suspected TB (n=63) were
      classified as: definite TB (Mycobacterium tuberculosis positive culture, n=21);
      presumed latent-TB infection (LTBI) (M. tuberculosis negative culture, no
      radiological features of active TB, a positive QuantiFERON-TB Gold In-Tube (QFT
      IT) test and a positive T-SPOT.TB test, n=24); and presumed non-TB/non-LTBI (M.
      tuberculosis negative culture, no radiological features of active TB, a negative
      QFT-IT test and a negative T-SPOT.TB test, n=18). Urine proteins, in the range of
      3-50 kDa, were collected, separated by a one-dimensional SDS-PAGE gel and
      digested using trypsin, after which high-performance liquid chromatography-tandem
      mass spectrometry was used to identify the urinary proteome. 10 mycobacterial
      proteins were observed exclusively in the urine of definite TB patients, while
      six mycobacterial proteins were found exclusively in the urine of presumed LTBI
      patients. In addition, a gene ontology enrichment analysis identified a panel of
      20 human proteins that were significant discriminators (p<0.05) for TB disease
      compared to no TB disease. Furthermore, seven common human proteins were
      differentially over- or under-expressed in the TB versus the non-TB group. These
      biomarkers hold promise for the development of new point-of-care diagnostics for
      TB. 

PMID- 24743963
TI  - Interferon-gamma responses to Mycobacterium tuberculosis-specific antigens in
      diabetes mellitus.

PMID- 24743964
TI  - Exhaled breath metabolomics as a noninvasive diagnostic tool for acute
      respiratory distress syndrome.
AB  - There is a need for biological markers of the acute respiratory distress syndrome
      (ARDS). Exhaled breath contains hundreds of metabolites in the gas phase, some of
      which reflect (patho)physiological processes. We aimed to determine the
      diagnostic accuracy of metabolites in exhaled breath as biomarkers of ARDS.
      Breath from ventilated intensive care unit patients (n=101) was analysed using
      gas chromatography and mass spectrometry during the first day of admission. ARDS
      was defined by the Berlin definition. Training and temporal validation cohorts
      were used. 23 patients in the training cohort (n=53) had ARDS. Three breath
      metabolites, octane, acetaldehyde and 3-methylheptane, could discriminate between
      ARDS and controls with an area under the receiver operating characteristic curve
      (AUC) of 0.80. Temporal external validation (19 ARDS cases in a cohort of 48)
      resulted in an AUC of 0.78. Discrimination was insensitive to adjustment for
      severity of disease, a direct or indirect cause of ARDS, comorbidities, or
      ventilator settings. Combination with the lung injury prediction score increased
      the AUC to 0.91 and improved net reclassification by 1.17. Exhaled breath
      analysis showed good diagnostic accuracy for ARDS, which was externally
      validated. These data suggest that exhaled breath analysis could be used for the
      diagnostic assessment of ARDS. 

PMID- 24743965
TI  - A haemodynamic study of pulmonary hypertension in chronic hypersensitivity
      pneumonitis.
AB  - Chronic hypersensitivity pneumonitis is a common fibrotic interstitial lung
      disease. The prevalence of pulmonary hypertension diagnosed by right heart
      catheterisation and its cardiopulmonary function findings in patients with
      chronic hypersensitivity pneumonitis are unknown. Consecutive symptomatic
      patients with chronic hypersensitivity pneumonitis were prospectively evaluated.
      All patients were submitted to right heart catheterisation, pulmonary function
      testing, a 6-min walk test, echocardiography, blood gas determination and N
      terminal pro-brain natriuretic peptide analyses. Nonhypoxaemic patients also
      underwent incremental cardiopulmonary exercise testing. 50 patients underwent
      right heart catheterisation; 25 (50%) of these had pulmonary hypertension and 22
      (44%) had a pre-capillary haemodynamic pattern. The patients with pre-capillary
      pulmonary hypertension had lower forced vital capacity (mean +/- sd 50 +/- 17%
      versus 69 +/- 22% predicted, p<0.01), carbon monoxide diffusing capacity (37 +/-
      12% versus 47 +/- 14% predicted, p<0.01), arterial oxygen tension (median
      (interquartile range) 59.0 (47.8-69.3) versus 73.0 (62.2-78.5) mmHg, p<0.01) and
      saturation after the 6-min walk test (78 +/- 8% versus 86 +/- 7%, p<0.01). In pre
      capillary pulmonary hypertension, oxygen uptake was also lower at the anaerobic
      threshold (41 +/- 11% versus 50 +/- 8% predicted, p=0.04) and at peak exercise
      (12.8 +/- 1.6 versus 15.0 +/- 2.5 mL . kg(-1) . min(-1), p=0.02). Pre-capillary
      pulmonary hypertension is common in symptomatic chronic hypersensitivity
      pneumonitis and is related to interstitial lung disease severity. Additionally,
      pulmonary hypertension is more prevalent in hypoxaemic patients with impaired
      lung function and exercise capacity.

PMID- 24743966
TI  - Benzodiazepine drug use and adverse respiratory outcomes among older adults with
      COPD.
AB  - Our purpose was to evaluate the association of new benzodiazepine use relative to
      non-use with adverse clinical respiratory outcomes among older adults with
      chronic obstructive pulmonary disease (COPD). This was a retrospective population
      based cohort study of Ontario, Canada, residents between 2003 and 2010. A
      validated algorithm was applied to health administrative data to identify adults
      aged 66 years and older with COPD. Relative risks (RRs) of several clinically
      important respiratory outcomes were examined within 30 days of incident
      benzodiazepine use compared with non-use, applying propensity score matching. New
      benzodiazepine users were at significantly higher risk for outpatient respiratory
      exacerbations (RR 1.45, 95% CI 1.36-1.54) and emergency room visits for COPD or
      pneumonia (RR 1.92, 95% CI 1.69-2.18) compared to non-users. Risk of
      hospitalisation for COPD or pneumonia was also increased in benzodiazepine users,
      but was nonsignificant (RR 1.09, 95% CI 1.00-1.20). There were no significant
      differences in intensive care unit admissions between the two groups and all
      cause mortality was slightly lower among new versus non-users. Benzodiazepines
      were associated with increased risk for several serious adverse respiratory
      outcomes among older adults with COPD. The findings suggest that decisions to use
      benzodiazepines in older patients with COPD need to consider potential adverse
      respiratory outcomes. 

PMID- 24743967
TI  - MicroRNA clusters: dysregulation in lung adenocarcinoma and COPD.
AB  - Lung adenocarcinoma and chronic obstructive pulmonary disease (COPD) are
      pulmonary diseases that share common aetiological factors (tobacco smoking) and
      probable dysregulated pathways. MicroRNAs (miRNAs) play an essential role in
      regulating numerous physiological and pathological processes. The purpose of this
      study was to assess global miRNA expression patterns in patients with COPD and/or
      adenocarcinoma to elucidate distinct regulatory networks involved in the
      pathogenesis of these two smoking-related diseases. Expression of 381 miRNAs was
      quantified by TaqMan Human MicroRNA A Array v2.0 in bronchoalveolar lavage fluid
      samples from 87 patients classified into four groups: COPD, adenocarcinoma,
      adenocarcinoma with COPD, and control (neither COPD nor adenocarcinoma). 11
      differentially expressed miRNAs were randomly selected for validation in an
      independent cohort of 40 patients. Distinct miRNA expression profiles were
      identified and validated for each pathological group, involving 66 differentially
      expressed miRNAs. Four miRNA clusters (the mir-17-92 cluster and its paralogues,
      mir-106a-363 and mir-106b-25; and the miR-192-194 cluster) were upregulated in
      patients with adenocarcinoma and one miRNA cluster (miR-132-212) was upregulated
      in patients with COPD. These results contribute to unravelling miRNA-controlled
      networks involved in the pathogenesis of adenocarcinoma and COPD, and provide new
      tools of potential use as biomarkers for diagnosis and/or therapeutic purposes. 

PMID- 24743968
TI  - Occupational irritants and asthma: an Estonian cross-sectional study of 34,000
      adults.
AB  - Occupational exposures make important contributions to asthma morbidity. The role
      of low/moderate level irritant exposures remains unclear. We aimed to determine
      which occupational exposures are associated with asthma in an eastern European
      country with low asthma prevalence. The Estonian Genome Center of University of
      Tartu collected data from 50 077 adults in 2002-2011. Asthma was assessed through
      a questionnaire regarding diagnosed diseases, current health status and
      medication. Exposures to 22 agents during the current and longest held jobs were
      estimated using an asthma-specific job-exposure matrix. Analyses included 34 015
      subjects (aged 18-65 years, 67.0% females), of which 1209 (3.6%) reported asthma
      (608 with physician-confirmed diagnosis). After adjusting for age, sex and
      smoking habits, lifetime occupational exposure to known asthmagens (20.4%) was
      significantly associated with physician-diagnosed asthma (OR 1.28, 95% CI 1.03
      1.59), especially high molecular weight agents (flour: OR 2.36, 95% CI 1.31-4.27;
      animals: OR 1.62, 95% CI 1.00-2.60). Exposure to low/moderate levels of irritants
      (17.4%) was associated with physician-diagnosed asthma (OR 1.88, 95% CI 1.48
      2.37). More pronounced associations were observed in subjects reporting current
      treated asthma. Beyond confirming the effect of known asthmagens (which are well
      known, mostly from observations in western countries), the results provide
      evidence for a role of low/moderate exposure to irritants. This finding, observed
      in a country with a low prevalence of asthma and atopy, provides new insight into
      the understanding of asthma heterogeneity. 

PMID- 24743969
TI  - Tuberculosis elimination: dream or reality? The case of Cyprus.

PMID- 24743970
TI  - SFTA3, a novel protein of the lung: three-dimensional structure, characterisation
      and immune activation.
AB  - The lung constantly interacts with numerous pathogens. Thus, complex local immune
      defence mechanisms are essential to recognise and dispose of these intruders.
      This work describes the detection, characterisation and three-dimensional
      structure of a novel protein of the lung (surfactant-associated protein 3
      (SFTA3/SP-H)) with putative immunological features. Bioinformatics, biochemical
      and immunological methods were combined to elucidate the structure and function
      of SFTA3. The tissue-specific detection and characterisation was performed by
      using electron microscopy as well as fluorescence imaging. Three-dimensional
      structure generation and analysis led to the development of specific antibodies
      and, as a consequence, to the localisation of a novel protein in human lung under
      consideration of cystic fibrosis, asthma and sepsis. In vitro experiments
      revealed that lipopolysaccharide induces expression of SFTA3 in the human lung
      alveolar type II cell line A549. By contrast, the inflammatory cytokines
      interleukin (IL)-1beta and IL-23 inhibit expression of SFTA3 in A549. Sequence-
      and structure-based prediction analysis indicated that the novel protein is
      likely to belong to the family of lung surfactant proteins. The results suggest
      that SFTA3 is an immunoregulatory protein of the lung with relevant protective
      functions during inflammation at the mucosal sites. 

PMID- 24743971
TI  - Quantitative imaging of airway liquid absorption in cystic fibrosis.
AB  - New measures are needed to rapidly assess emerging treatments for cystic fibrosis
      (CF) lung disease. Using an imaging approach, we evaluated the absorptive
      clearance of the radiolabeled small molecule probe diethylene triamine penta
      acetic acid (DTPA) as an in vivo indicator of changes in airway liquid
      absorption. DTPA absorption and mucociliary clearance rates were measured in 21
      patients with CF (12 adults and nine children) and nine adult controls using
      nuclear imaging. The effect of hypertonic saline on DTPA absorption was also
      studied. In addition, in vitro studies were conducted to identify the
      determinants of transepithelial DTPA absorption. CF patients had significantly
      increased rates of DTPA absorption compared with control subjects but had similar
      mucociliary clearance rates. Treatment with hypertonic saline resulted in a
      decrease in DTPA absorption and an increase in mucociliary clearance in 11 out of
      11 adult CF patients compared with treatment with isotonic saline. In vitro
      studies revealed that ~ 50% of DTPA absorption can be attributed to
      transepithelial fluid transport. Apically applied mucus impedes liquid and DTPA
      absorption. However, mucus effects become negligible in the presence of an
      osmotic stimulus. Functional imaging of DTPA absorption provides a quantifiable
      marker of immediate response to treatments that promote airway surface liquid
      hydration.

PMID- 24743972
TI  - Theoretical studies on effective metal-to-ligand charge transfer characteristics
      of novel ruthenium dyes for dye sensitized solar cells.
AB  - The development of ruthenium dye-sensitizers with highly effective metal-to
      ligand charge transfer (MLCT) characteristics and narrowed transition energy gaps
      are essential for the new generation of dye-sensitized solar cells. Here, we
      designed a novel anchoring ligand by inserting the cyanovinyl-branches inside the
      anchoring ligands of selected highly efficient dye-sensitizers and studied their
      intrinsic optical properties using theoretical methods. Our calculated results
      show that the designed ruthenium dyes provide good performances as sensitizers
      compared to the selected efficient dyes, because of their red-shift in the UV
      visible absorption spectra with an increase in the absorption intensity, smaller
      energy gaps and thereby enhancing MLCT transitions. We found that, the designed
      anchoring ligand acts as an efficient "electron-acceptor" which boosts electron
      transfer from a -NCS ligand to this ligand via a Ru-bridge, thus providing a way
      to lower the transition energy gap and enhance the MLCT transitions. 

PMID- 24743973
TI  - The effects of insulin-like growth factor 1 and growth hormone on human meibomian
      gland epithelial cells.
AB  - IMPORTANCE: A phase 1 study has reported that dry eye disease is the most common
      adverse effect of human exposure to the antibody figitumumab, an anticancer drug
      that prevents insulin-like growth factor 1 (IGF-1) from binding to its receptor.
      We hypothesized that the mechanism underlying this effect is the inhibition of
      IGF-1 action in epithelial cells of the meibomian gland. OBJECTIVES: To test the
      hypothesis that IGF-1 stimulates meibomian gland function in vitro and to examine
      whether growth hormone, a closely related hormone of IGF-1, has the same effect.
      DESIGN, SETTING, AND MATERIAL: Immortalized human meibomian gland epithelial
      cells were cultured in the presence or the absence of IGF-1, growth hormone, and
      an IGF-1 receptor-blocking antibody. Signaling pathways, cell proliferation,
      neutral lipid staining, and a key protein involved in lipid biogenesis were
      evaluated. INTERVENTION: Application of IGF-1 and growth hormone to human
      meibomian gland epithelial cells. MAIN OUTCOMES AND MEASURES: Immunoblotting,
      cell counting, and neutral lipid staining. RESULTS Insulin-like growth factor 1
      activated the phosphoinositol 3-kinase/Akt and forkhead box O1 pathways (showing
      a dose-dependent effect on immunoblotting), stimulated cellular proliferation
      (about 1.8-fold increase in cell number), increased sterol regulatory element
      binding protein 1 expression (about 3-fold increase on immunoblotting), and
      promoted lipid accumulation in human meibomian gland epithelial cells (about 2
      fold increase in lipid staining). These IGF-1 actions, which may be blocked by
      cotreatment with the anti-IGF-1 antibody, were accompanied by inconsistent
      effects on extracellular signal-regulated kinase phosphorylation. We were not
      able to demonstrate activation of Akt, forkhead box O1, extracellular signal
      regulated kinase, Janus kinase 2, or signal transducers and activators of
      transcription 5, induced cell proliferation, or lipid accumulation in these cells
      by growth hormone application. CONCLUSIONS AND RELEVANCE: Our results support the
      hypothesis that IGF-1 acts on human meibomian gland epithelial cells and may
      explain why treatment with figitumumab, the IGF-1 inhibitor, causes dry eye
      disease. Ophthalmic care for dry eye disease may be needed when patients with
      cancer undergo treatment with drugs that inhibit IGF-1 action.

PMID- 24743974
TI  - ADHD in the College Setting: Current Perceptions and Future Vision.
AB  - OBJECTIVE: To assess perceptions concerning ADHD among U.S. college healthcare
      providers. METHOD: A 37-question survey was conducted from October 4 to December
      2, 2010. Participants were contacted via mail or telephone and compensated for
      participation. RESULTS: Thirty-eight percent of the respondents (physicians, n =
      59; nurses, n = 138; directors, n = 101) viewed ADHD as a "problem"/"very much a
      problem" at their institution. Referrals for evaluation came from students (84%),
      psychologists/counselors (68%), or the institution (68%). Although 48% of
      respondents felt "comfortable"/"very comfortable" in their ability to recognize
      ADHD, 92% referred students for evaluation. Most respondents (>90%) agreed
      medication use may be warranted; 52% of respondents who treat ADHD or consult
      with a specialist (from 95% of physicians to 31% of directors) prescribed
      pharmacotherapy. CONCLUSION: Although college healthcare providers recognize the
      importance of treating ADHD, their discomfort in diagnosing and treating ADHD
      represents a barrier to care for college students.

PMID- 24743975
TI  - Adult ADHD screening in alcohol-dependent patients using the Wender-Utah Rating
      Scale and the adult ADHD Self-Report Scale.
AB  - OBJECTIVE: The aim was to analyze the psychometric properties of two screening
      instruments, Wender-Utah Rating Scale (WURS) that evaluates childhood ADHD and
      Adult ADHD Self-Report Scales (ASRS) that assesses symptoms in adulthood, in
      alcohol-dependent patients. METHOD: A total of 355 outpatients were included.
      Conners' adult ADHD diagnostic interview results were used as a gold standard in
      childhood and adulthood ADHD. RESULTS: The WURS with a 41 cutoff had a
      sensitivity of 79.6% and a specificity of 60.3%. The ASRS with a 14 cutoff had a
      sensitivity of 86.7% and specificity of 66.1%. Analyzing both rating scales in
      combination, it was observed that patients with positive ASRS and WURS presented
      a sensitivity of 92.3%. Patients with positive ASRS, but negative WURS, presented
      a specificity of 73.6%. CONCLUSION: WURS and ASRS are useful tools in the
      diagnosis of adult ADHD in alcohol-dependent patients; with the use of both
      instruments, the psychometric properties are substantially improved.

PMID- 24743976
TI  - Daytime Sleepiness in Adults With ADHD: A Pilot Trial With a Multiple Sleep
      Latency Test.
AB  - OBJECTIVE: To evaluate sleep latency (SL) during the multiple sleep latency test
      (MSLT) and subjective daytime sleepiness in adult ADHD and controls. METHOD:
      Subjective daytime sleepiness was assessed by Epworth Sleepiness Scale (ESS) in
      27 unmedicated adults with ADHD and in 182 controls. Thirteen ADHD patients and
      26 controls underwent MSLT after one night of polysomnography (PSG). RESULTS:
      Mean MSLT-SL was 10.6 +/- 4.8 min in ADHD and 12.2 +/- 4.2 min in controls
      (n.s.). Mean ESS score was 9.3 +/- 4.9 points in ADHD and 6.9 +/- 3.4 points in
      controls (p < .005). MSLT-SL and ESS scores correlated inversely by trend (r = 
      .45, p < .1) but not with ADHD symptoms or ADHD subtype. CONCLUSION: Adults with
      ADHD do not differ from controls in mean MSLT-SL but experience increased
      subjective daytime sleepiness. Patients with subjective higher daytime tiredness
      fell asleep faster during MSLT.

PMID- 24743977
TI  - Psychiatric Comorbidities in a New Zealand Sample of Adults With ADHD.
AB  - OBJECTIVE: To examine the rates of psychiatric comorbidities within a New Zealand
      sample of adults with ADHD compared with a community control group. METHOD: We
      merged six data sets to obtain a sample of 222 adults (158 ADHD, 64 controls).
      Comorbidities were assessed using the Structured Clinical Interview for
      Diagnostic and Statistical Manual of Mental Disorders (4th ed. text rev. [DSM-IV
      TR]) Axis-I disorders. RESULTS: Both groups were equivalent in IQ, socioeconomic
      status, gender, education, income levels, and age. Lifetime rates of psychiatric
      disorders were significantly higher in the ADHD group (83%) versus the control
      group (52%) with higher rates of major depressive disorder (MDD; 65% vs. 36%),
      social phobia (31% vs. 11%), substance abuse (26% vs. 8%), and alcohol abuse (32%
      vs. 14%). Within the ADHD group, other than a group difference in specific
      phobias, there were no gender differences. CONCLUSION: The findings are
      consistent with international research; adults with ADHD in New Zealand have
      higher rates of psychiatric disorders than the general population.

PMID- 24743978
TI  - ADHD symptomatology and risky health, driving, and financial behaviors in
      college: the mediating role of sensation seeking and effortful control.
AB  - OBJECTIVE: To examine the extent to which effortful control (EC) and sensation
      seeking (SS) tendencies explain the association between the severity of ADHD
      symptoms and risky behaviors. METHOD: Participants included 555 college students
      (66% females) who completed self-report measures assessing their ADHD symptoms,
      EC abilities, SS tendencies, and risky health (e.g., substance use) and
      driving/financial behaviors (e.g., misuse of credit cards). RESULTS: Severity of
      college students' ADHD symptoms, EC abilities, and SS tendencies were related to
      all risky behaviors. Multiple mediational analyses further indicated that
      students' SS tendencies significantly mediated the association between ADHD
      symptoms and the risky health factor but not the risky driving/financial factor.
      EC, however, significantly mediated the association between ADHD symptoms and
      both the risky health and driving/financial factors. CONCLUSION: The current
      study provides initial data showing potentially different mechanisms that explain
      the link between college students' severity of ADHD symptoms and risky behaviors.

PMID- 24743979
TI  - 2,3-butanediol production from cellobiose by engineered Saccharomyces cerevisiae.
AB  - Production of renewable fuels and chemicals from cellulosic biomass is a critical
      step towards energy sustainability and reduced greenhouse gas emissions.
      Microbial cells have been engineered for producing chemicals from cellulosic
      sugars. Among these chemicals, 2,3-butanediol (2,3-BDO) is a compound of interest
      due to its diverse applications. While microbial production of 2,3-BDO with high
      yields and productivities has been reported, there are concerns associated with
      utilization of potential pathogenic bacteria and inefficient utilization of
      cellulosic sugars. To address these problems, we engineered 2,3-BDO production in
      Saccharomyces cerevisiae, especially from cellobiose, a prevalent sugar in
      cellulosic hydrolysates. Specifically, we overexpressed alsS and alsD from
      Bacillus subtilis to convert pyruvate into 2,3-BDO via alpha-acetolactate and
      acetoin in an engineered cellobiose fermenting S. cerevisiae. Under oxygen
      limited conditions, the resulting strain was able to produce 2,3-BDO. Still,
      major carbon flux went to ethanol, resulting in substantial amounts of ethanol
      produced as a byproduct. To enhance pyruvate flux to 2,3-BDO through elimination
      of the pyruvate decarboxylation reaction, we employed a deletion mutant of both
      PDC1 and PDC5 for producing 2,3-BDO. When a cellobiose utilization pathway,
      consisting of a cellobiose transporter and intracellular beta-glucosidase, and
      the 2,3-BDO producing pathway were introduced in a pyruvate decarboxylase
      deletion mutant, the resulting strain produced 2,3-BDO without ethanol production
      from cellobiose under oxygen-limited conditions. A titer of 5.29 g/l 2,3-BDO with
      a productivity of 0.22 g/l h and yield of 0.29 g 2,3-BDO/g cellobiose was
      attained. These results suggest the possibility of producing 2,3-BDO safely and
      sustainably from cellulosic hydrolysates.

PMID- 24743980
TI  - Soil microbial community responses to antibiotic-contaminated manure under
      different soil moisture regimes.
AB  - Sulfadiazine (SDZ) is an antibiotic frequently administered to livestock, and it
      alters microbial communities when entering soils with animal manure, but
      understanding the interactions of these effects to the prevailing climatic regime
      has eluded researchers. A climatic factor that strongly controls microbial
      activity is soil moisture. Here, we hypothesized that the effects of SDZ on soil
      microbial communities will be modulated depending on the soil moisture
      conditions. To test this hypothesis, we performed a 49-day fully controlled
      climate chamber pot experiments with soil grown with Dactylis glomerata (L.).
      Manure-amended pots without or with SDZ contamination were incubated under a
      dynamic moisture regime (DMR) with repeated drying and rewetting changes of >20 %
      maximum water holding capacity (WHCmax) in comparison to a control moisture
      regime (CMR) at an average soil moisture of 38 % WHCmax. We then monitored
      changes in SDZ concentration as well as in the phenotypic phospholipid fatty acid
      and genotypic 16S rRNA gene fragment patterns of the microbial community after 7,
      20, 27, 34, and 49 days of incubation. The results showed that strongly changing
      water supply made SDZ accessible to mild extraction in the short term. As a
      result, and despite rather small SDZ effects on community structures, the PLFA
      derived microbial biomass was suppressed in the SDZ-contaminated DMR soils
      relative to the CMR ones, indicating that dynamic moisture changes accelerate the
      susceptibility of the soil microbial community to antibiotics.

PMID- 24743981
TI  - Role of autophagy and its significance in cellular homeostasis.
AB  - Autophagy is a catabolic pathway that regulates homeostasis in cells. It is an
      exceptional pathway of membrane trafficking. Autophagy is characterized by the
      formation of double-membrane vesicles; autophagosomes that are responsible for
      delivering damaged organelle and extra proteins to lysosome for recycling. A
      series of actions including environmental and genetic factors are responsible for
      induction of autophagy. In the past few decades, the research on autophagy has
      been immensely expanded because it is a vital process in maintaining cellular
      balance as well as deeply connected with pathogenesis of a number of diseases.
      The aim of this review is to present an overview of modern work on autophagy and
      highlight some essential genetic role in the induction of autophagy. There is an
      emerging need to identify, quantify, and manipulate the pathway of autophagy, due
      to its close relationship with a variety of developmental pathways and functions
      especially in cancer, diabetes, neurodegenerative disorders, and infectious
      diseases. 

PMID- 24743982
TI  - Construction of expression vectors for metabolic engineering of the vanillin
      producing actinomycete Amycolatopsis sp. ATCC 39116.
AB  - Amycolatopsis sp. ATCC 39116 is able to synthesize the important flavoring agent
      vanillin from cheap natural substrates. The bacterium is therefore of great
      interest for the industry and used for the fermentative production of vanillin.
      In order to improve the production of natural vanillin with Amycolatopsis sp.
      ATCC 39116, the strain has been genetically engineered to optimize the metabolic
      flux towards the desired product. Extensive metabolic engineering was hitherto
      hampered, due to the lack of genetic tools like functional promoters and
      expression vectors. In this study, we report the establishment of a plasmid-based
      gene expression system for Amycolatopsis sp. ATCC 39116 that allows a further
      manipulation of the genotype. Four new Escherichia coli-Amycolatopsis shuttle
      vectors harboring different promoter elements were constructed, and the
      functionality of these regulatory elements was proven by the expression of the
      reporter gene gusA, encoding a beta-glucuronidase. Glucuronidase activity was
      detected in all plasmid-harboring strains, and remarkable differences in the
      expression strength of the reporter gene depending on the used promoter were
      observed. The new expression vectors will promote the further genetic engineering
      of Amycolatopsis sp. ATCC 39116 to get insight into the metabolic network and to
      improve the strain for a more efficient industrial use. 

PMID- 24743984
TI  - An AIL/IL-based liquid/liquid extraction system for the purification of His
      tagged proteins.
AB  - A sorbent based on affinity ionic liquid (AIL), triazacyclononane-ionic liquid,
      was synthesized, characterized, and applied to the extraction of histidine (His)
      tagged proteins from aqueous buffer to ionic liquid (IL) phase. The adsorbed His
      tagged proteins could be back-extracted from the IL phase to the aqueous buffer
      with an imidazole solution. The specific binding of His-tagged proteins with
      AIL/IL could be affected by a few factors including the ionic strength and
      coordinated metal ions. In the case of His-tagged enhanced green fluorescent
      protein (EGFP), the maximum binding capacity of Cu(2+)-AIL/IL reached 2.58
      MUg/MUmol under the optimized adsorption conditions. The eluted His-tagged EGFP
      kept fluorescent and remained active through the purification process. Moreover,
      a tandem extraction process successively using Cu(2+)-AIL/IL and Zn(2+)-AIL/IL
      systems was developed, which was proven very efficient to obtain the ultimate
      protein with a purity of about 90 %. An effective reclamation method for the
      AIL/IL extraction system was further established. The sorbent could be easily
      regenerated by removing metal ions with EDTA and the followed reimmobilization of
      metal ions. Easy handling of the presented M(2+)-AIL/IL system and highly
      specific ability to absorb His-tagged proteins make it attractive and potentially
      applicable in biomolecular separation.

PMID- 24743985
TI  - Proteomic analyses of the phase transition from acidogenesis to solventogenesis
      using solventogenic and non-solventogenic Clostridium acetobutylicum strains.
AB  - The fermentation carried out by the solvent-producing bacterium, Clostridium
      acetobutylicum, is characterized by two distinct phases: acidogenic and
      solventogenic phases. Understanding the cellular physiological changes occurring
      during the phase transition in clostridial fermentation is important for the
      enhanced production of solvents. To identify protein changes upon entry to
      stationary phase where solvents are typically produced, we herein analyzed the
      proteomic profiles of the parental wild type C. acetobutylicum strains, ATCC 824,
      the non-solventogenic strain, M5 that has lost the solventogenic megaplasmid
      pSOL1, and the synthetic simplified alcohol forming strain, M5 (pIMP1E1AB)
      expressing plasmid-based CoA-transferase (CtfAB) and aldehyde/alcohol
      dehydrogenase (AdhE1). A total of 68 protein spots, corresponding to 56 unique
      proteins, were unambiguously identified as being differentially present after the
      phase transitions in the three C. acetobutylicum strains. In addition to changes
      in proteins known to be involved in solventogenesis (AdhE1 and CtfB), we
      identified significant alterations in enzymes involved in sugar transport and
      metabolism, fermentative pathway, heat shock proteins, translation, and amino
      acid biosynthesis upon entry into the stationary phase. Of these, four increased
      proteins (AdhE1, CAC0233, CtfB and phosphocarrier protein HPr) and six decreased
      proteins (butyrate kinase, ferredoxin:pyruvate oxidoreductase, phenylalanyl-tRNA
      synthetase, adenylosuccinate synthase, pyruvate kinase and valyl-tRNA synthetase)
      showed similar patterns in the two strains capable of butanol formation.
      Interestingly, significant changes of several proteins by post-translational
      modifications were observed in the solventogenic phase. The proteomic data from
      this study will improve our understanding on how cell physiology is affected
      through protein levels patterns in clostridia. 

PMID- 24743983
TI  - Protein expression in Pichia pastoris: recent achievements and perspectives for
      heterologous protein production.
AB  - Pichia pastoris is an established protein expression host mainly applied for the
      production of biopharmaceuticals and industrial enzymes. This methylotrophic
      yeast is a distinguished production system for its growth to very high cell
      densities, for the available strong and tightly regulated promoters, and for the
      options to produce gram amounts of recombinant protein per litre of culture both
      intracellularly and in secretory fashion. However, not every protein of interest
      is produced in or secreted by P. pastoris to such high titres. Frequently,
      protein yields are clearly lower, particularly if complex proteins are expressed
      that are hetero-oligomers, membrane-attached or prone to proteolytic degradation.
      The last few years have been particularly fruitful because of numerous activities
      in improving the expression of such complex proteins with a focus on either
      protein engineering or on engineering the protein expression host P. pastoris.
      This review refers to established tools in protein expression in P. pastoris and
      highlights novel developments in the areas of expression vector design, host
      strain engineering and screening for high-level expression strains. Breakthroughs
      in membrane protein expression are discussed alongside numerous commercial
      applications of P. pastoris derived proteins. 

PMID- 24743986
TI  - Signal peptide of cellulase.
AB  - Cellulase is an enzyme playing a crucial role in biotechnology industries ranging
      from textile to biofuel because of tremendous amount of cellulose produced in
      plant. In order to improve cellulase productivity, huge resource has been spent
      in search for good cellulases from microorganism in remote areas and in creation
      of ideal cellulase by engineering. However, not much attention is given to the
      secretion of cellulases from cell into extracellular space, where a cellulase
      plays its enzymatic role. In this minireview, the signal peptides, which lead
      secreted proteins to specific secretion systems and scatter in literature, are
      reviewed. The patterns of signal peptides are checked against 4,101 cellulases
      documented in UniProtKB, the largest protein database in the world, to determine
      how these cellulases are secreted. Simultaneous review on both literature and
      cellulases from the database not only provides updated knowledge on signal
      peptides but also indicates the gap in our research. 

PMID- 24743987
TI  - Radiocesium derived from the Fukushima Daiichi Nuclear Power Plant accident in
      seabed sediments: initial deposition and inventories.
AB  - Since the accident at Fukushima Daiichi Nuclear Power Plant (1FNPP), significant
      levels of anthropogenic radionuclides have been detected in seabed sediments off
      the east coast of Japan. In this paper, the approximate amount of accident
      derived radiocesium in seabed sediments off Fukushima, Miyagi and Ibaraki
      prefectures was estimated from a sediment integration algorithm. As of October
      2011, about half a year after the accident, the total amount of sedimentary 134Cs
      was 0.20+/-0.06 PBq (decay corrected to March 11, 2011) and more than 90% of the
      radiocesium was accumulated in the regions shallower than 200 m depth. The large
      inventory in the coastal sediments was attributed to effective adsorption of
      dissolved radiocesium onto suspended particles and directly to sediments in the
      early post-accident stage. Although rivers are also an important source to supply
      radiocesium to the coastal regions, this flux was much lower than that of the
      above-mentioned process within half a year after the accident.

PMID- 24743988
TI  - Efficient library preparation for next-generation sequencing analysis of genome
      wide epigenetic and transcriptional landscapes in embryonic stem cells.
AB  - Gene expression in embryonic stem (ES) cells is regulated in part by a network of
      transcription factors, epigenetic regulators, and histone modifications that
      influence the underlying chromatin in a way that is conducive or repressive for
      transcription. Advances in next-generation sequencing technology have allowed for
      the genome-wide analysis of chromatin constituents and protein-DNA interactions
      at high resolution in ES cells and other stem cells. While many studies have
      surveyed genome-wide profiles of a few factors and expression changes at a fixed
      time point in undifferentiated ES cells, few have utilized an integrative
      approach to simultaneously survey protein-DNA interactions, histone
      modifications, and expression programs during ES cell self-renewal and
      differentiation. To identify transcriptional networks that regulate pluripotency
      and differentiation, it is important to generate high-quality genome-wide maps of
      transcription factors, chromatin factors, and histone modifications and to survey
      global gene expression profiles. Here, to interrogate genome-wide profiles of
      chromatin features and to survey global gene expression programs in ES cells, we
      describe protocols for efficient library construction for next-generation
      sequencing of ChIP-Seq and RNA-Seq samples. 

PMID- 24743989
TI  - Analysis of next-generation sequencing data using Galaxy.
AB  - The extraordinary throughput of next-generation sequencing (NGS) technology is
      outpacing our ability to analyze and interpret the data. This chapter will focus
      on practical informatics methods, strategies, and software tools for transforming
      NGS data into usable information through the use of a web-based platform, Galaxy.
      The Galaxy interface is explored through several different types of example
      analyses. Instructions for running one's own Galaxy server on local hardware or
      on cloud computing resources are provided. Installing new tools into a personal
      Galaxy instance is also demonstrated. 

PMID- 24743990
TI  - edgeR for differential RNA-seq and ChIP-seq analysis: an application to stem cell
      biology.
AB  - The edgeR package, an R-based tool within the Bioconductor project, offers a
      flexible statistical framework for detection of changes in abundance based on
      counts. In this chapter, we illustrate the use of edgeR on a human embryonic stem
      cell dataset, in particular for RNA-seq and ChIP-seq data. We focus on a step-by
      step statistical analysis of differential expression, going from raw data to a
      list of putative differentially expressed genes and give examples of integrative
      analysis using the ChIP-seq data. We emphasize data quality spot checks and the
      use of positive controls throughout the process and give practical
      recommendations for reproducible research. 

PMID- 24743991
TI  - Use model-based Analysis of ChIP-Seq (MACS) to analyze short reads generated by
      sequencing protein-DNA interactions in embryonic stem cells.
AB  - Model-based Analysis of ChIP-Seq (MACS) is a computational algorithm for
      identifying genome-wide protein-DNA interaction from ChIP-Seq data. MACS combines
      multiple modules to process aligned ChIP-Seq reads for either transcription
      factor or histone modification by removing redundant reads, estimating fragment
      length, building signal profile, calculating peak enrichment, and refining and
      reporting peak calls. In this protocol, we provide a detailed demonstration of
      how to apply MACS to analyze ChIP-Seq datasets related to protein-DNA
      interactions in embryonic stem cells (ES cells). Instruction on how to interpret
      and visualize the results is also provided. MACS is an open-source and is
      available from http://github.com/taoliu/MACS.

PMID- 24743993
TI  - Identifying stem cell gene expression patterns and phenotypic networks with
      AutoSOME.
AB  - Stem cells have the unique property of differentiation and self-renewal and play
      critical roles in normal development, tissue repair, and disease. To promote
      systems-wide analysis of cells and tissues, we developed AutoSOME, a machine
      learning method for identifying coordinated gene expression patterns and
      correlated cellular phenotypes in whole-transcriptome data, without prior
      knowledge of cluster number or structure. Here, we present a facile primer
      demonstrating the use of AutoSOME for identification and characterization of stem
      cell gene expression signatures and for visualization of transcriptome networks
      using Cytoscape. This protocol should serve as a general foundation for gene
      expression cluster analysis of stem cells, with applications for studying
      pluripotency, multi-lineage potential, and neoplastic disease. 

PMID- 24743992
TI  - Spatial clustering for identification of ChIP-enriched regions (SICER) to map
      regions of histone methylation patterns in embryonic stem cells.
AB  - Chromatin states are the key to embryonic stem cell pluripotency and
      differentiation. Chromatin immunoprecipitation (ChIP) followed by high-throughput
      sequencing (ChIP-Seq) is increasingly used to map chromatin states and to
      functionally annotate the genome. Many ChIP-Seq profiles, especially those of
      histone methylations, are noisy and diffuse. Here we describe SICER (Zang et al.,
      Bioinformatics 25(15):1952-1958, 2009), an algorithm specifically designed to
      identify disperse ChIP-enriched regions with high sensitivity and specificity.
      This algorithm has found a lot of applications in epigenomic studies. In this
      Chapter, we will demonstrate in detail how to run SICER to delineate ChIP
      enriched regions and assess their statistical significance, and to identify
      regions of differential enrichment when two chromatin states are compared. 

PMID- 24743994
TI  - Visualization and clustering of high-dimensional transcriptome data using GATE.
AB  - The potential gains from advances in high-throughput experimental molecular
      biology techniques are commonly not fully realized since these techniques often
      produce more data than can be easily organized and visualized. To address these
      problems, GATE (Grid-Analysis of Time-Series Expression) was developed. GATE is
      an integrated software platform for the analysis and visualization of high
      dimensional time-series datasets, which allows flexible interrogation of time
      series data against a wide range of databases of prior knowledge, thus linking
      observed molecular dynamics to potential genetic, epigenetic, and signaling
      mechanisms responsible for observed dynamics. This article provides a brief guide
      to using GATE effectively. 

PMID- 24743995
TI  - Interpreting and visualizing ChIP-seq data with the seqMINER software.
AB  - Chromatin immunoprecipitation coupled high-throughput sequencing (ChIP-seq) is a
      common method to study in vivo protein-DNA interactions at the genome-wide level.
      The processing, analysis, and biological interpretation of gigabyte datasets,
      generated by several ChIP-seq runs, is a challenging task for biologists. The
      seqMINER platform has been designed to handle, compare, and visualize different
      sequencing datasets in a user-friendly way. Different analysis methods are
      applied to understand common and specific binding patterns of single or multiple
      datasets to answer complex biological questions. Here, we give a detailed
      protocol about the different analysis modules implemented in the recent version
      of seqMINER. 

PMID- 24743996
TI  - A description of the Molecular Signatures Database (MSigDB) Web site.
AB  - Annotated lists of genes help researchers to prioritize their own lists of
      candidate genes and to plan follow-up studies. The Molecular Signatures Database
      (MSigDB) is one of the most widely used knowledge base repositories of annotated
      sets of genes involved in biochemical pathways, signaling cascades, expression
      profiles from research publications, and other biological concepts. Here we
      provide an overview of MSigDB and its online analytical tools. 

PMID- 24743997
TI  - Use of genome-wide RNAi screens to identify regulators of embryonic stem cell
      pluripotency and self-renewal.
AB  - Embryonic stem cells (ESCs) are characterized by two defining features:
      pluripotency and self-renewal. They hold tremendous promise for both basic
      research and regenerative medicine. To fully realize their potentials, it is
      important to understand the molecular mechanisms regulating ESC pluripotency and
      self-renewal. The development of RNA interference (RNAi) technology has
      revolutionized functional genetic studies in mammalian cells. In recent years,
      genome-wide RNAi screens have been adopted to systematically study ESC biology,
      and have uncovered many previously unknown regulators, including transcription
      factors, chromatin remodelers, and posttranscriptional modulators. Here, we
      describe a method for the identification of regulators of ESC pluripotency and
      self-renewal using RNAi screens, as well as assays for further validation and
      characterization of the identified candidates. With modifications, this method
      can also be adapted to study the fate specification events during ESC
      differentiation. 

PMID- 24743998
TI  - Correlating histone modification patterns with gene expression data during
      hematopoiesis.
AB  - Hematopoietic stem cells (HSC) in mammals are an ideal system to study
      differentiation. While transcription factors (TFs) control the differentiation of
      HSCs to distinctive terminal blood cells, accumulating evidence suggests that
      chromatin structure and modifications constitute another critical layer of gene
      regulation. Recent genome-wide studies based on next-generation sequencing reveal
      that histone modifications are linked to gene expression and contribute to
      hematopoiesis. Here, we briefly review the bioinformatics aspects for ChIP-Seq
      and RNA-Seq data analysis with applications to the epigenetic studies of
      hematopoiesis and provide a practical guide to several basic data analysis
      methods. 

PMID- 24743999
TI  - In vitro maturation and in vitro fertilization of mouse oocytes and
      preimplantation embryo culture.
AB  - Epigenetic regulation of gene expression in the germline is important for
      reproductive success of mammals. Misregulation of genes whose expression is
      correlated with reproductive success may result in subfertility or infertility.
      To study epigenetic events that occur during oocyte maturation and
      preimplantation embryo development, it is important to generate large numbers of
      ovarian follicles and embryos. Oocyte maturation can be modeled using in vitro
      maturation (IVM), which is a system of maturing ovarian follicles in a culture
      dish. In addition, fertilization and early embryogenesis can be modeled using in
      vitro fertilization (IVF), which involves the fertilization of mature oocytes
      with capacitated sperm in a culture dish. Here, we describe protocols for in
      vitro maturation (IVM) and in vitro fertilization (IVF) of mouse oocytes and
      preimplantation embryo culture. These protocols are suitable for the study of
      oocyte and embryo biology and the production of embryonic mice. 

PMID- 24744000
TI  - Derivation and manipulation of trophoblast stem cells from mouse blastocysts.
AB  - The trophoblast is the first lineage to undergo differentiation during mammalian
      development. In the preimplantation blastocyst embryo, two cell types are present
      including the inner cell mass (ICM) and the trophectoderm (TE). ICM cells exhibit
      pluripotent potential, or the capacity to give rise to all cells represented in
      the adult organism, while TE cells are multipotent and are therefore only capable
      of differentiating into trophoblast lineages represented in the placenta. The TE
      is essential for implantation of the embryo into the uterine tissue, formation of
      trophoblast lineages represented in the placenta, and exchange of nutrients and
      waste between the embryo and the mother. Trophoblast stem (TS) cells, which can
      be derived from the TE of preimplantation embryos in the presence of external
      signals such as FGF4, can self-renew indefinitely, and because they are capable
      of differentiating into epithelial lineages of the trophoblast, TS cells are a
      useful in vitro model to study the biology of the trophoblast including
      epigenetic regulation of gene expression. In this chapter we describe protocols
      for derivation of TS cells from mouse blastocysts, culture conditions that
      promote self-renewal and differentiation, and methods to transduce TS cells with
      lentiviral particles encoding shRNAs. These protocols are sufficient for
      efficient derivation of TS cells and robust RNAi knockdown of target genes in TS
      cells. 

PMID- 24744001
TI  - Conversion of epiblast stem cells to embryonic stem cells using growth factors
      and small molecule inhibitors.
AB  - Stem cell in vitro culture is a useful model system to study mechanisms
      underlying transitions between defined cell states. Epiblast stem cells, in
      addition to being capable of somatic differentiation, can be converted to a more
      primitive embryonic stem cell-like state, by overexpression of specific
      transcription factors. Here, we describe a reliable method to accomplish-and
      potentially further study-the transgene-independent reversion from epiblast stem
      cells to ES cells using administration of specific growth factors and small
      molecule inhibitors. 

PMID- 24744002
TI  - Generation of induced pluripotent stem cells using chemical inhibition and three
      transcription factors.
AB  - Generation of induced pluripotent stem (iPS) cells from differentiated cells has
      traditionally been performed by overexpressing four transcription factors: Oct4,
      Sox2, Klf4, and c-Myc. However, inclusion of c-Myc in the reprogramming cocktail
      can lead to expansion of transformed cells that are not fully reprogrammed, and
      studies have demonstrated that c-Myc reactivation increases tumorigenicity in
      chimeras and progeny mice. Moreover, chemical inhibition of Wnt signaling has
      been shown to enhance reprogramming efficiency. Here, we describe a modified
      protocol for generating iPS cells from murine fibroblasts using chemical
      inhibition and overexpression of three transcription factors. Using this
      protocol, we observed robust conversion to iPS cells while maintaining minimal
      contamination of partially reprogrammed transformed colonies. 

PMID- 24744003
TI  - Transdifferentiation of mouse fibroblasts and hepatocytes to functional neurons.
AB  - Nuclear reprogramming by defined transcription factors became of broad interest
      in 2006 with the work of Takahashi and Yamanaka (Cell 126:663-676, 2006), but the
      first example of cell fate reshaping via ectopic expression of transcription
      factor was provided back in 1987 when Davis and colleagues induced features of a
      muscle cell in fibroblast using the muscle transcription factor MyoD (Davis et
      al., Cell 51:987-1000, 1987). In 2010 our laboratory described how forced
      expression of the three neuronal transcription factors Ascl1, Brn2, and Myt1l
      rapidly converts mouse fibroblasts into neuronal cells that exhibit biochemical
      and electrophysiological properties of neurons. We named these cells induced
      neuronal cells (iN cells) (Vierbuchen et al., Nature 463:1035-1041, 2010;
      Vierbuchen and Wernig, Nat Biotechnol 29:892-907, 2011). Interestingly, iN cells
      can also be derived from defined endodermal cells such as primary hepatocytes,
      suggesting the existence of a more general reprogramming paradigm (Marro et al.,
      Cell Stem Cell 9:374-382, 2011). In this chapter we describe the detailed methods
      used to attain the direct conversion. 

PMID- 24744004
TI  - Direct lineage conversion of pancreatic exocrine to endocrine Beta cells in vivo
      with defined factors.
AB  - Pancreatic exocrine cells can be directly converted to insulin(+) beta cells by
      adenoviral-mediated expression of three transcription factors Pdx1, Mafa, and
      Ngn3 in the adult mouse pancreas (Zhou et al., Nature 455(7213):627-632, 2008).
      This direct reprogramming approach offers a strategy to replenish beta-cell mass
      and may be further developed as a potential future treatment for diabetes. Here,
      we provide a detailed protocol for inducing exocrine to beta-cell reprogramming
      in mice. We also describe key analyses we routinely use to assess the phenotype
      and function of reprogrammed cells. 

PMID- 24744005
TI  - Direct reprogramming of cardiac fibroblasts to cardiomyocytes using microRNAs.
AB  - The therapeutic administration of microRNAs represents an innovative
      reprogramming strategy with which to advance cardiac regeneration and
      personalized medicine. Recently, a distinct set of microRNAs was found capable of
      converting murine fibroblasts to cardiomyocyte-like cells in vitro. Further
      treatment with JAK inhibitor I significantly enhanced the efficiency of the
      microRNA-mediated reprogramming (Jayawardena et al., Circ Res 110(11):1465-1473,
      2012). This novel technique serves as an initial tool for switching the cell fate
      of cardiac fibroblasts toward the cardiomyocyte lineage using microRNAs. As the
      budding field of reprogramming biology develops, we hope that a thorough
      examination of the chemical, physical, and temporal parameters determining
      reprogramming efficiency and maturation will enable a better understanding of the
      mechanisms governing cardiac cell fate and provide new approaches for drug
      discovery and therapy for cardiovascular diseases. 

PMID- 24744006
TI  - Reprogramming somatic cells into pluripotent stem cells using miRNAs.
AB  - Reversal of terminally differentiated somatic cells to ground-state pluripotency
      has rejuvenated our hopes of generating patient-specific stem cells for
      therapeutic use in regenerative medicine and drug screening. Originally generated
      using defined exogenous protein-coding DNA, several methods have been described
      in reprogramming somatic cells into iPSC. Majority of published methods seek to
      improve or refine the techniques of reprogramming. This chapter describes
      reprogramming to pluripotency using miRNAs. 

PMID- 24744007
TI  - Evaluation of molecular markers for the diagnosis of Mycobacterium bovis.
AB  - Mycobacterium tuberculosis complex (MTC) comprises a group of bacteria that have
      a high degree of genetic similarity. Two species in this group, Mycobacterium
      tuberculosis and Mycobacterium bovis, are the main cause of human and bovine
      tuberculosis, respectively. M. bovis has a broader host range that includes
      humans; thus, the differentiation of mycobacterium is of great importance for
      epidemiological and public health considerations and to optimize treatment. The
      current study aimed to evaluate primers and molecular markers described in the
      literature to differentiate M. bovis and M. tuberculosis by PCR. Primers JB21/22,
      frequently cited in scientific literature, presented in our study the highest
      number of errors to identify M. bovis or M. tuberculosis (73%) and primers
      Mb.400, designed to flank region of difference 4 (RD4), were considered the most
      efficient (detected all M. bovis tested and did not detect any M. tuberculosis
      tested). Although also designed to flank RD4, primers Mb.115 misidentified eight
      samples due to primer design problems. The results showed that RD4 is the ideal
      region to differentiate M. bovis from other bacteria classified in MTC, but
      primer design should be considered carefully.

PMID- 24744008
TI  - Biogenic silica-metal phosphate (metal = Ca, Fe or Zn) nanocomposites:
      fabrication from rice husk and their biomedical applications.
AB  - In this investigation, we fabricated biogenic silica-metal phosphate
      nanocomposites (BSMPNs) using rice husk from agricultural waste as a silica
      source. The morphologies and dimensions of the synthesized nanocomposites were
      analyzed using transmission electron microscopy (TEM). Fourier-transform infrared
      spectroscopy results confirmed that metal phosphate crystals were formed with the
      biogenic silica. The X-ray diffraction patterns of the BSMPNs showed the presence
      of hexagonal calcium and iron phosphate and orthorhombic zinc phosphate
      nanoparticles embedded in the matrix of biogenic silica. The TEM images suggested
      that spherical and irregularly shaped tiny particles with dimensions between 50
      and 100 nm were dispersed in the biogenic silica. The in vitro biological
      properties of the nanocomposites were studied by a cell viability assay and
      through the analysis of microscopy images. The cytocompatibility studies proved
      that the material was nontoxic and had excellent biocompatibility with human
      mesenchymal stem cells. The synthetic route for these nanocomposites is
      interesting and may be helpful in the fabrication of various novel silica-based
      composites and in the exploitation of eco-friendly agricultural biomass. Our
      results revealed that these nanocomposites can be used in bone tissue
      engineering. 

PMID- 24744009
TI  - Osteochondral transplantation for the treatment of osteochondral defects at the
      talus with the Diamond twin system((r)) and graft harvesting from the posterior
      femoral condyles.
AB  - BACKGROUND: The aim of this study is to analyze clinical results after
      osteochondral cylinder transplantation for osteochondral defects at the medial or
      lateral talar dome using the Diamond twin system (Karl Storz). We hypothesize
      that grafts harvesting from the posterior femoral condyles are associated with
      less donor site morbidity than reported by previous studies. METHODS: We have
      surgically treated 20 patients with an osteochondral defect of the talus by
      osteochondral transplantation with the Diamond twin system via an osteotomy of
      the ankle. The osteochondral cylinders were harvested from the posterior aspects
      of the femoral condyles of the ipsilateral knee. The defects at donor site were
      filled with a bone substitute of tricalcium phosphate (Synthricer, Karl Storz).
      The mean age was 25.4 years. After a mean time of 12.6 months, the screws at the
      medial malleolus were removed and an arthroscopy was performed. The functional
      outcome was evaluated with the visual analog scale for pain at walking, running,
      stair climbing, quality of life at the time of implant removal and at a mean
      follow-up of 25.8 months. Activity was assessed with the Tegner scale. Knee
      function was evaluated with the Lysholm score. RESULTS: In one case, the
      osteochondral cylinder did not heal and an osteochondral fragment was removed
      arthroscopically. In all other cases, the osteochondral cylinder was stable with
      surrounding cartilage. The average ICRS Cartilage Repair Assessment was 10.1
      points (+/-1.3). All malleolar osteotomies healed radiologically. In 15 patients,
      a synovectomy and local debridement of the ankle were performed at second-look
      arthroscopy. Ankle pain at walking, running and stair climbing as measured by a
      visual analog scale (10-0) decreased significantly from preoperatively to the
      first follow-up (mean 12.6 months) and to the second follow-up (mean 25.8
      months). The ankle-related quality of life increased significantly from
      preoperatively to postoperatively. There was no significant change in the Lysholm
      score. The activity measured with the Tegner activity scale increased
      significantly from preoperatively to the last follow-up, but only two out of nine
      patients continued pivoting sports. CONCLUSIONS: Autologous osteochondral
      grafting with the Diamond twin system is a reliable treatment option for
      symptomatic osteochondral defects of the talus. After 1 year, the majority of
      patients had still some complaints. However, after screw removal and second-look
      arthroscopy, the pain and ankle-related quality of life further improved.
      CLINICAL RELEVANCE: The donor site morbidity after graft harvesting from the
      posterior aspects of the femoral condyles is lower than previously reported.

PMID- 24744010
TI  - Integration of navigated brain stimulation data into radiosurgical planning:
      potential benefits and dangers.
AB  - BACKGROUND: Radiosurgical treatment of brain lesions near motor or language
      eloquent areas requires careful planning to achieve the optimal balance between
      effective dose prescription and preservation of function. Navigated brain
      stimulation (NBS) is the only non-invasive modality that allows the
      identification of functionally essential areas by electrical stimulation or
      inhibition of cortical neurons analogous to the gold-standard of intraoperative
      electrical mapping. OBJECTIVE: To evaluate the feasibility of NBS data
      integration into the radiosurgical environment, and to analyze the influence of
      NBS data on the radiosurgical treatment planning for lesions near or within motor
      or language eloquent areas of the brain. METHODS: Eleven consecutive patients
      with brain lesions in presumed motor or language eloquent locations eligible for
      radiosurgical treatment were mapped with NBS. The radiosurgical team
      prospectively analyzed the data transfer and classified the influence of the
      functional NBS information on the radiosurgical treatment planning using a
      standardized questionnaire. RESULTS: The semi-automatized data transfer to the
      radiosurgical planning workstation was flawless in all cases. The NBS data
      influenced the radiosurgical treatment planning procedure as follows: improved
      risk-benefit balancing in all cases, target contouring in 0 %, dose plan
      modification in 81.9 %, reduction of radiation dosage in 72.7 % and treatment
      indication in 63.7 % of the cases. CONCLUSIONS: NBS data integration into
      radiosurgical treatment planning is feasible. By mapping the spatial relationship
      between the lesion and functionally essential areas, NBS has the potential to
      improve radiosurgical planning safety for eloquently located lesions.

PMID- 24744011
TI  - Transplantation of neurotrophin-3-expressing bone mesenchymal stem cells improves
      recovery in a rat model of spinal cord injury.
AB  - BACKGROUND: This study aimed to investigate the therapeutic effects of
      transplanting neutrophin-3 (NT-3)-expressing bone marrow-derived mesenchymal stem
      cells (BMSCs) in a rat model of spinal cord injury (SCI). METHODS: Forty-eight
      adult female Sprague-Dawley rats were randomly assigned to three groups: the
      control, BMSC, and NT-3-BMSC groups. BMSCs were infected with NT-3-DsRed or DsRed
      lentivirus and injected into the cerebrospinal fluid (CSF) via lumbar puncture
      (LP) 7 days after SCI in the NT-3-BMSC and BMSC groups, respectively. The hind
      limb motor function of all rats was recorded using the Basso, Beattie, and
      Bresnahan (BBB) locomotor rating scale on days 1, 3, 7, 14, 21, 28, and 35 after
      transplantation. Haematoxylin-eosin (HE) staining, immunofluorescence labelling,
      and western blotting were performed at the final time point. RESULTS: Expressions
      of NT-3, brain-derived neurotrophic factor (BDNF), and vascular endothelial
      growth factor (VEGF) proteins increased significantly in the NT-3-BMSC group, and
      hind-limb locomotor functions improved significantly in the NT-3-BMSC group
      compared with the other two groups. The cystic cavity area was smallest in the NT
      3-BMSC group. In the NT-3-BMSC group, neurofilament 200 (NF200) and glial
      fibrillary acidic protein (GFAP) expression levels around the lesions were
      significantly increased and decreased, respectively. CONCLUSIONS: Our findings
      demonstrate that transplantation of NT-3 gene-modified BMSCs via LP can
      strengthen the therapeutic benefits of BMSC transplantation. We observed that
      these modified cells increased locomotor function recovery, promoted nerve
      regeneration, and improved the injured spinal cord microenvironment, suggesting
      that it could be a promising treatment for SCI.

PMID- 24744012
TI  - A phylogenomic and molecular marker based proposal for the division of the genus
      Borrelia into two genera: the emended genus Borrelia containing only the members
      of the relapsing fever Borrelia, and the genus Borreliella gen. nov. containing
      the members of the Lyme disease Borrelia (Borrelia burgdorferi sensu lato
      complex).
AB  - The genus Borrelia contains two groups of organisms: the causative agents of Lyme
      disease and their relatives and the causative agents of relapsing fever and their
      relatives. These two groups are morphologically indistinguishable and are
      difficult to distinguish biochemically. In this work, we have carried out
      detailed comparative genomic analyses on protein sequences from 38 Borrelia
      genomes to identify molecular markers in the forms of conserved signature
      inserts/deletions (CSIs) that are specifically found in the Borrelia homologues,
      and conserved signature proteins (CSPs) which are uniquely present in Borrelia
      species. Our analyses have identified 31 CSIs and 82 CSPs that are uniquely
      shared by all sequenced Borrelia species, providing molecular markers for this
      group of organisms. In addition, our work has identified 7 CSIs and 21 CSPs which
      are uniquely found in the Lyme disease Borrelia species and eight CSIs and four
      CSPs that are specific for members of the relapsing fever Borrelia group.
      Additionally, 38 other CSIs, in proteins which are uniquely found in Borrelia
      species, also distinguish these two groups of Borrelia. The identified CSIs and
      CSPs provide novel and highly specific molecular markers for identification and
      distinguishing between the Lyme disease Borrelia and the relapsing fever Borrelia
      species. We also report the results of average nucleotide identity (ANI) analysis
      on Borrelia genomes and phylogenetic analysis for these species based upon 16S
      rRNA sequences and concatenated sequences for 25 conserved proteins. These
      analyses also support the distinctness of the two Borrelia clades. On the basis
      of the identified molecular markers, the results from ANI and phylogenetic
      studies, and the distinct pathogenicity profiles and arthropod vectors used by
      different Borrelia spp. for their transmission, we are proposing a division of
      the genus Borrelia into two separate genera: an emended genus Borrelia,
      containing the causative agents of relapsing fever and a novel genus, Borreliella
      gen. nov., containing the causative agents of Lyme disease. 

PMID- 24744013
TI  - Chemical shift imaging at 3 Tesla: effect of echo time on assessing bone marrow
      abnormalities.
AB  - OBJECTIVE: Our purpose is to test the effect of varied in-phase (IP) and opposed
      phase (OP) sequence order on characterizing marrow signal changes at 3T.
      MATERIALS AND METHODS: The study was HIPAA compliant and IRB approved. Informed
      consent was waived. At 3T, IP and OP sequences were acquired in three patients
      with biopsy-proven osteosarcomas, using two methods: approach 1 (OP acquisition
      before IP acquisition) and approach 2 (OP after IP). Signal intensity (SI)
      measurements in 12 locations of biopsy-proven osteosarcoma and in six locations
      with normal bone marrow were performed independently by two experienced
      musculoskeletal radiologists. The signal intensity ratio (SIR) was measured
      within the marrow where there was T1 signal lower than skeletal muscle. A SIR <
      20 % on the OP compared with IP imaging was considered positive for marrow
      replacement, while SIR > = 20 % was considered negative. Interobserver agreement
      was measured by the Lin concordance correlation coefficient (CCC). RESULTS: In 75
      % (18/24) of locations within the biopsy-proven tumors, the SIR was >20 % (SI
      drop more than 20 % in OP compared to IP) using approach 2 and in 100 % (24/24)
      of the locations the SIR was <20 % (SI drop less than 20 % in OP compared to IP)
      using approach 1, indicating a high percentage of false-negative results by
      approach 2, and no false-negative results with approach 1. There was good
      agreement between observer measurement (CCC = 0.96). CONCLUSIONS: At 3T, the OP
      sequence should be acquired prior to the IP sequence, because susceptibility
      artifacts on a later-acquired OP sequence may lead to an erroneous interpretation
      of marrow signal abnormalities.

PMID- 24744014
TI  - Comparison of the critical shoulder angle in radiographs and computed tomography.
AB  - OBJECTIVE: The critical shoulder angle (CSA) is an indicator of degenerative
      shoulder pathologies. CSAs above 35 degrees  are associated with degenerative
      rotator cuff disease, whereas values below 30 degrees  are common in
      osteoarthritis of the glenohumeral joint. Measurements are usually performed on
      radiographs; however, no data have been reported regarding the reliability of CT
      scan measurements between different readers or the reproducibility of
      measurements from radiographs to CT scans. The purpose of our study was to
      clarify whether CSA measurements on radiographs and CT scans of the same patients
      show similar values. MATERIALS AND METHODS: CSA measurements of 60 shoulders (59
      patients) were performed on radiographs and multiplanar reconstructions of
      corresponding CT scans. Inter-reader reliability and inter-method correlation
      were calculated. RESULTS: The mean discrepancy between readers was only 0.2
      degrees  (SD +/-1.0 degrees ) on radiographs. CT scan measurements showed a mean
      discrepancy of 0.3 degrees  (SD +/-1.2 degrees ). The inter-reader reliability
      was 0.993 for radiographs and 0.989 for CT scans. There was a very strong inter
      method correlation between the CSA measured on radiographs and CT scans
      (Spearman's rho = 0.974). The mean differences between angles on radiographs and
      CT measurements were -0.05 degrees  (SD +/-1.2 degrees ) and 0.1 degrees  (SD +/
      1.2 degrees ), respectively. CONCLUSION: Measurements of the CSA on anterior
      posterior radiographs and CT scans are highly correlated, and inter-modality
      differences are negligible.

PMID- 24744015
TI  - Pseudomonas helmanticensis sp. nov., isolated from forest soil.
AB  - A bacterial strain, OHA11(T), was isolated during the course of a study of
      phosphate-solubilizing bacteria occurring in a forest soil from Salamanca, Spain.
      The 16S rRNA gene sequence of strain OHA11(T) shared 99.1% similarity with
      respect to Pseudomonas baetica a390(T), and 98.9% similarity with the type
      strains of Pseudomonas jessenii, Pseudomonas moorei, Pseudomonas umsongensis,
      Pseudomonas mohnii and Pseudomonas koreensis. The analysis of housekeeping genes
      rpoB, rpoD and gyrB confirmed its phylogenetic affiliation to the genus
      Pseudomonas and showed similarities lower than 95% in almost all cases with
      respect to the above species. Cells possessed two polar flagella. The respiratory
      quinone was Q9. The major fatty acids were C16 : 0, C18 : 1omega7c and summed
      feature 3 (C16 : 1omega7c/iso-C15 : 0 2-OH). The strain was oxidase-, catalase-
      and urease-positive, positive for arginine dihydrolase but negative for nitrate
      reduction, beta-galactosidase production and aesculin hydrolysis. It was able to
      grow at 31  degrees C and at pH 11. The DNA G+C content was 58.1 mol%. DNA-DNA
      hybridization results showed values lower than 49% relatedness with respect to
      the type strains of the seven closest related species. Therefore, the combined
      genotypic, phenotypic and chemotaxonomic data support the classification of
      strain OHA11(T) to a novel species of the genus Pseudomonas, for which the name
      Pseudomonas helmanticensis sp. nov. is proposed. The type strain is OHA11(T) ( =
      LMG 28168(T) = CECT 8548(T)).

PMID- 24744016
TI  - Pseudomonas hussainii sp. nov., isolated from droppings of a seashore bird, and
      emended descriptions of Pseudomonas pohangensis, Pseudomonas benzenivorans and
      Pseudomonas segetis.
AB  - Two Gram-staining-negative, aerobic, rod-shaped, non-spore-forming bacterial
      strains that are motile by a monopolar flagellum, designated CC-AMH-11(T) and CC
      AMHZ-5, were isolated from droppings of a seashore bird off the coast of Hualien,
      Taiwan. The strains showed 99.7% mutual pairwise 16S rRNA gene sequence
      similarity, while exhibiting <96.2% sequence similarity to strains of other
      species of the genus Pseudomonas (95.7-95.9% similarity with type species,
      Pseudomonas aeruginosa LMG 1242T), and formed a distinct co-phyletic lineage in
      the phylogenetic trees. The common major fatty acids (>5% of the total) were C18
      : 1omega7c and/or C18 : 1omega6c (summed feature 8), C16 : 1omega6c and/or C16 :
      1omega7c (summed feature 3), C16 : 0 and C12 : 0. Phosphatidylethanolamine,
      phosphatidylglycerol, diphosphatidylglycerol, phosphatidylserine, an unidentified
      lipid and an unidentified phospholipid were detected as common polar lipids. The
      DNA G+C contents of strains CC-AMH-11(T) and CC-AMHZ-5 were 61.1 and 61.6 mol%,
      respectively. The common major respiratory quinone was ubiquinone 9 (Q-9), and
      the predominant polyamine was putrescine. The DNA-DNA hybridization obtained
      between the two strains was 79.0% (reciprocal value 89.4% using CC-AMHZ-5 DNA as
      the probe). The very high 16S rRNA gene sequence similarity and DNA-DNA
      relatedness and the poorly distinguishable phenotypic features witnessed between
      CC-AMH-11(T) and CC-AMHZ-5 suggested unambiguously that they are two distinct
      strains of a single genomic species. However, the strains also showed several
      genotypic and phenotypic characteristics that distinguished them from other
      closely related species of Pseudomonas. Thus, the strains are proposed to
      represent a novel species of Pseudomonas, for which the name Pseudomonas
      hussainii sp. nov. is proposed. The type strain is CC-AMH-11(T) ( = JCM 19513(T)
      = BCRC 80696(T)); a second strain of the same species is CC-AMHZ-5 ( = JCM 19512
      = BCRC 80697). In addition, emended descriptions of the species Pseudomonas
      pohangensis, Pseudomonas benzenivorans and Pseudomonas segetis are also proposed.

PMID- 24744017
TI  - Gordonibacter urolithinfaciens sp. nov., a urolithin-producing bacterium isolated
      from the human gut.
AB  - Urolithins are dibenzopyranone metabolites that exert anti-inflammatory activity
      in vivo and are produced by the gut microbiota from the dietary polyphenols
      ellagic acid (EA) and ellagitannins. However, the bacteria involved in this
      process remain unknown. We report here a novel bacterium, strain CEBAS 1/15P(T),
      capable of metabolizing EA to urolithins, that was isolated from healthy human
      faeces and characterized by determining phenotypic, biochemical and molecular
      methods. The strain was related to Gordonibacter pamelaeae 7-10-1-b(T), the type
      and only reported strain of the only species of the genus Gordonibacter, with
      about 97% 16S rRNA gene sequence similarity; they were both obligately anaerobic,
      non-spore-forming, Gram-stain-positive, short-rods/coccobacilli and metabolized
      only small numbers of carbon sources. L-Fucose, D-fructose, turanose, D
      galacturonic acid and alpha-ketobutyric acid were metabolized by strain CEBAS
      1/15P(T), while G. pamelaeae was negative for metabolism of these compounds. The
      whole-cell fatty acids consisted predominantly of saturated fatty acids (70%);
      strain CEBAS 1/15P(T) differed significantly from G. pamelaeae in the major fatty
      acid, which was C18 : 1omega9c, while anteiso-C15 : 0 was the major component for
      G. pamelaeae. The presence of a number of different fatty acid peaks, especially
      C19 : 0 cyclo and C18 : 1omega6c, was also indicative of distinct species. Six
      glycolipids (GL1-6) were recognized, while, in G. pamelaeae, only four
      glycolipids were described. On the basis of these data, the novel species
      Gordonibacter urolithinfaciens sp. nov. is described, with strain CEBAS 1/15P(T)
      ( = DSM 27213(T) = CCUG 64261(T)) as the type strain.

PMID- 24744018
TI  - Bradyrhizobium manausense sp. nov., isolated from effective nodules of Vigna
      unguiculata grown in Brazilian Amazonian rainforest soils.
AB  - Root nodule bacteria were trapped within cowpea (Vigna unguiculata) in soils with
      different cultivation histories collected from the Amazonian rainforest in
      northern Brazil. Analysis of the 16S rRNA gene sequences of six strains (BR
      3351(T), BR 3307, BR 3310, BR 3315, BR 3323 BR and BR 3361) isolated from cowpea
      nodules showed that they formed a distinct group within the genus Bradyrhizobium,
      which was separate from previously identified type strains. Phylogenetic analyses
      of three housekeeping genes (glnII, recA and rpoB) revealed that Bradyrhizobium
      huanghuaihaiense CCBAU 23303(T) was the most closely related type strain (96%
      sequence similarity or lower). Chemotaxonomic data, including fatty acid profiles
      (predominant fatty acids being C16 : 0 and summed feature 8), the slow growth
      rate and carbon compound utilization patterns supported the assignment of the
      strains to the genus Bradyrhizobium. The results of DNA-DNA hybridizations,
      antibiotic resistance and physiological tests differentiated these novel strains
      from the most closely related species of the genus Bradyrhizobium with validly
      published names. Symbiosis-related genes for nodulation (nodC) and nitrogen
      fixation (nifH) grouped the novel strains of the genus Bradyrhizobium together
      with Bradyrhizobium iriomotense strain EK05(T), with 94% and 96% sequence
      similarity, respectively. Based on these data, these six strains represent a
      novel species for which the name Brabyrhizobium manausense sp. nov. (BR 3351(T) =
      HAMBI 3596(T)), is proposed.

PMID- 24744019
TI  - Loktanella maritima sp. nov. isolated from shallow marine sediments.
AB  - An aerobic, Gram-stain-negative, non-motile bacterium, KMM 9530(T), was isolated
      from a sediment sample collected from the Sea of Japan seashore. Comparative 16S
      rRNA gene sequence analysis positioned novel strain KMM 9530(T) in the genus
      Loktanella as a separate line adjacent to Loktanella sediminilitoris KCTC
      32383(T), Loktanella tamlensis JCM 14020(T) and Loktanella maricola JCM 14564(T)
      with 98.5-98.2% sequence similarity. Strain KMM 9530(T) was characterized by its
      weak hydrolytic capacity and inability to assimilate most organic substrates. The
      major isoprenoid quinone was Q-10, polar lipids consisted of phosphatidylcholine,
      phosphatidylglycerol, diphosphatidylglycerol, an unknown phospholipid, an unknown
      aminolipid and unknown lipids, and the major fatty acid was C18 : 1omega7c. On
      the basis of phylogenetic analysis, DNA-DNA hybridization and phenotypic
      characterization, it can be concluded that the novel strain KMM 9530(T)
      represents a novel species in the genus Loktanella, for which the name Loktanella
      maritima sp. nov. is proposed. The type strain of the species is KMM 9530(T) ( =
      NRIC 0919(T) = JCM 19807(T)).

PMID- 24744020
TI  - Janibacter indicus sp. nov., isolated from hydrothermal sediment of the Indian
      Ocean.
AB  - A Gram-staining-positive, aerobic and non-motile strain, 0704P10-1(T), was
      isolated from hydrothermal sediment of the Indian Ocean. Phylogenetic, phenotypic
      and chemotaxonomic data for the organism supported that it belonged to the genus
      Janibacter. Strain 0704P10-1(T) showed 97.2-98.7% 16S rRNA gene sequence
      similarities to the type strains of recognized members of the genus Janibacter.
      It contained meso-diaminopimelic acid as the diagnostic diamino acid in the cell
      wall. MK-8(H4) was the only menaquinone detected. The major fatty acids were iso
      C16 : 0, C17 : 1omega8c and 10-methyl C17 : 0. Meanwhile, the results of DNA-DNA
      hybridization studies and other physiological and biochemical tests allowed the
      genotypic and phenotypic differentiation of strain 0704P10-1(T) from closely
      related species. Thus, strain 0704P10-1(T) represents a novel species of the
      genus Janibacter, for which the name Janibacter indicus sp. nov. is proposed. The
      type strain is 0704P10-1(T) ( = LMG 27493(T) = CGMCC 1.12511(T)).

PMID- 24744022
TI  - Update on treatments for dystonia.
AB  - Oral medication, botulinum toxin injections, and deep brain stimulation are the
      current mainstays of treatment for dystonia. In addition, physical and other
      supportive therapies may help prevent further complications (eg, contractures)
      and improve function. This review discusses evidence-based medical treatment of
      dystonia with an emphasis on recent advances in treatment. We will also review
      the current treatment approaches and suggest ways in which these therapies can be
      applied to individuals with dystonia. 

PMID- 24744021
TI  - Resting state functional magnetic resonance imaging in Parkinson's disease.
AB  - Neuroimaging advances over the past several decades have provided increased
      understanding of the structural and functional brain changes that occur with
      Parkinson's disease (PD). Examination of resting state functional magnetic
      resonance imaging (rs-fMRI) provides a noninvasive method that focuses on low
      frequency spontaneous fluctuations in the blood-oxygenation-level-dependent
      signal that occurs when an individual is at rest. Several analysis methods have
      been developed and used to explore how PD affects resting state activity and
      functional connectivity, and the purpose of this review is to highlight the
      critical advances made thus far. Some discrepancies in the rs-fMRI and PD
      literature exist, and we make recommendations for consideration in future
      studies. The rs-fMRI technique holds promise for investigating brain changes
      associated with the motor and nonmotor symptoms of PD, and for revealing
      important variations across large-scale networks of the brain in PD. 

PMID- 24744023
TI  - Traumatic optic neuropathy and second optic nerve injuries.
AB  - IMPORTANCE: Current controversy about the primary treatment of traumatic optic
      neuropathy (TON) has anchored on final vision following injury, but, to our
      knowledge, no study has examined the effect of different treatments on regaining
      and protecting optic nerve reserve or on the outcome of second optic nerve
      injuries. OBJECTIVE: To assess vision improvement in patients treated by various
      methods who have a second incidence of TON. DESIGN, SETTING, AND PARTICIPANTS:
      Retrospective medical record review of 12 patients with a second TON seen in an
      18-year period (mean follow-up, 11.3 months) at a single tertiary care
      oculoplastic practice. INTERVENTIONS: Observation, high-dose corticosteroids,
      optic nerve decompression, or high-dose corticosteroids plus optic nerve
      decompression. MAIN OUTCOMES AND MEASURES: Change in vision on the Snellen eye
      chart. RESULTS All second TON events involved the same-side optic nerve as
      initially injured, and with observation alone, corticosteroids, or
      corticosteroids and partial optic canal decompression, all patients had vision
      improvement after their initial injury (P = .004). However, following the second
      optic nerve injury, most patients' vision fell to the pretreatment level of the
      first injury, and subsequent management of the second injury with corticosteroids
      and/or optic canal decompression provided little or no vision return (P = .05).
      In contrast, optic canal decompressions performed for 91 primary TON injuries
      resulted in 82.4% having some degree of vision improvement. CONCLUSIONS AND
      RELEVANCE: Patients with TON may have a second optic nerve insult, and vision
      recovery from the second event may be limited regardless of primary treatment
      choice.

PMID- 24744024
TI  - An overview on selection marker genes for transformation of Saccharomyces
      cerevisiae.
AB  - For genetic manipulation of yeast, numerous selection marker genes have been
      employed. These include prototrophic markers, markers conferring drug resistance,
      autoselection markers, and counterselectable markers. This chapter describes the
      different classes of selection markers and provides a number of examples for
      different applications. 

PMID- 24744025
TI  - Natural and modified promoters for tailored metabolic engineering of the yeast
      Saccharomyces cerevisiae.
AB  - The ease of highly sophisticated genetic manipulations in the yeast Saccharomyces
      cerevisiae has initiated numerous initiatives towards development of
      metabolically engineered strains for novel applications beyond its traditional
      use in brewing, baking, and wine making. In fact, baker's yeast has become a key
      cell factory for the production of various bulk and fine chemicals. Successful
      metabolic engineering requires fine-tuned adjustments of metabolic fluxes and
      coordination of multiple pathways within the cell. This has mostly been achieved
      by controlling gene expression at the transcriptional level, i.e., by using
      promoters with appropriate strengths and regulatory properties. Here we present
      an overview of natural and modified promoters, which have been used in metabolic
      pathway engineering of S. cerevisiae. Recent developments in creating promoters
      with tailor-made properties are also discussed. 

PMID- 24744026
TI  - Tools for genetic engineering of the yeast Hansenula polymorpha.
AB  - Hansenula polymorpha is a methylotrophic yeast species that has favorable
      properties for heterologous protein production and metabolic engineering. It
      provides an attractive expression platform with the capability to secrete high
      levels of commercially important proteins. Over the past few years many efforts
      have led to advances in the development of this microbial host including the
      generation of expression vectors containing strong constitutive or inducible
      promoters and a large array of dominant and auxotrophic markers. Moreover, highly
      efficient transformation procedures used to generate genetically stable strains
      are now available. Here, we describe these tools as well as the methods for
      genetic engineering of H. polymorpha. 

PMID- 24744027
TI  - Molecular tools and protocols for engineering the acid-tolerant yeast
      Zygosaccharomyces bailii as a potential cell factory.
AB  - Microorganisms offer a tremendous potential as cell factories, and they are
      indeed used by humans for centuries for biotransformations. Among them, yeasts
      combine the advantage of unicellular state with a eukaryotic organization, and,
      in the era of biorefineries, their biodiversity can offer solutions to specific
      process constraints. Zygosaccharomyces bailii, an ascomycetales budding yeast, is
      widely known for its peculiar tolerance to various stresses, among which are
      organic acids. Despite the possibility to apply with this yeast some of the
      molecular tools and protocols routinely used to manipulate Saccharomyces
      cerevisiae, adjustments and optimizations are necessary. Here, we describe in
      detail protocols for transformation, for target gene disruption or gene
      integration, and for designing episomal expression plasmids helpful for
      developing and further studying the yeast Z. bailii. 

PMID- 24744028
TI  - Strains and molecular tools for recombinant protein production in Pichia
      pastoris.
AB  - Within the last two decades, the methylotrophic yeast Pichia pastoris has become
      an important alternative to E. coli or mammalian cell lines for the production of
      recombinant proteins. Easy handling, strong promoters, and high cell density
      cultivations as well as the capability of posttranslational modifications are
      some of the major benefits of this yeast. The high secretion capacity and low
      level of endogenously secreted proteins further promoted the rapid development of
      a versatile Pichia pastoris toolbox. This chapter reviews common and new "Pichia
      tools" and their specific features. Special focus is given to expression strains,
      such as different methanol utilization, protease-deficient or glycoengineered
      strains, combined with application highlights. Different promoters and signal
      sequences are also discussed. 

PMID- 24744029
TI  - Methods for efficient high-throughput screening of protein expression in
      recombinant Pichia pastoris strains.
AB  - The methylotrophic yeast Pichia pastoris is becoming one of the favorite
      industrial workhorses for protein expression. Due to the widespread use of
      integration vectors, which generates significant clonal variability, screening
      methods allowing assaying hundreds of individual clones are of particular
      importance. Here we describe methods to detect and analyze protein expression,
      developed in a 96-well format for high-throughput screening of recombinant P.
      pastoris strains. The chapter covers essentially three common scenarios: (1) an
      enzymatic assay for proteins expressed in the cell cytoplasm, requiring cell
      lysis; (2) a whole-cell assay for a fungal cytochrome P450; and (3) a
      nonenzymatic assay for detection and quantification of tagged protein secreted
      into the supernatant. 

PMID- 24744031
TI  - Generation of arming yeasts with active proteins and peptides via cell surface
      display system: cell surface engineering, bio-arming technology.
AB  - The cell surface display system in yeast enables the innovative strategy for
      improving cellular functions in a wide range of applications such as biofuel
      production, bioremediation, synthesis of valuable chemicals, recovery of rare
      metal ions, development of biosensors, and high-throughput screening of
      proteins/peptides library. Display of enzymes for polysaccharide degradation
      enables the construction of metabolically engineered whole-cell biocatalyst owing
      to the accessibility of the displayed enzymes to high-molecular-weight
      polysaccharides. In addition, along with fluorescence-based activity evaluation,
      fluorescence-activated cell sorting (FACS), and yeast cell chip, the cell surface
      display system is an effective molecular tool for high-throughput screening of
      mutated proteins/peptides library. In this article, we describe the methods for
      cell surface display of proteins/peptides of interest on yeast, evaluation of
      display efficiency, and harvesting of the displayed proteins/peptides from cell
      surface. 

PMID- 24744030
TI  - Synthetic RNA switches for yeast metabolic engineering: screening recombinant
      enzyme libraries.
AB  - Directed evolution is a powerful technique for increasing the activity of poorly
      active enzymes, for example when an enzyme is engineered to accept a new
      substrate or function in a new environment. Since enzyme activity greatly depends
      on the enzyme environment, screening should be performed under the same
      conditions as the ultimate application of the enzyme. When an enzyme will be used
      in live cells, RNA biosensors offer a powerful and flexible method of linking the
      desired phenotype, production of a small molecule of interest, to an easily
      measured phenotype, such as fluorescence. Here, we describe methods for screening
      enzyme libraries using an RNA biosensor, showing examples from the evolution of a
      P450 monooxygenase. 

PMID- 24744032
TI  - Genetic engineering of industrial Saccharomyces cerevisiae strains using a
      selection/counter-selection approach.
AB  - Gene modification of laboratory yeast strains is currently a very straightforward
      task thanks to the availability of the entire yeast genome sequence and the high
      frequency with which yeast can incorporate exogenous DNA into its genome.
      Unfortunately, laboratory strains do not perform well in industrial settings,
      indicating the need for strategies to modify industrial strains to enable strain
      development for industrial applications. Here we describe approaches we have used
      to genetically modify industrial strains used in winemaking. 

PMID- 24744033
TI  - Evolutionary engineering of yeast.
AB  - Evolutionary engineering is an inverse metabolic engineering strategy which is
      based on increasing genetic diversity and screening large populations for desired
      phenotypes. This strategy is highly advantageous in certain situations over
      rational metabolic engineering approaches, since there is little or no
      requirement of detailed genetic background information for the trait of interest.
      Here, we describe the experimental methodology for selecting stress-resistant
      yeast strains via evolutionary engineering approach by either serial batch or
      chemostat cultivations. 

PMID- 24744034
TI  - Determination of a dynamic feeding strategy for recombinant Pichia pastoris
      strains.
AB  - The knowledge of certain strain specific parameters of recombinant P. pastoris
      strains is required to be able to set up a feeding regime for fed-batch
      cultivations. To date, these parameters are commonly determined either by time
      consuming and labor-intensive continuous cultivations or by several, consecutive
      fed-batch cultivations. Here, we describe a fast method based on batch
      experiments with methanol pulses to extract certain strain characteristic
      parameters, which are required to set up a dynamic feeding strategy for P.
      pastoris strains based on specific substrate uptake rate (q(s)). We further
      describe in detail the course of actions which have to be taken to obtain the
      desired dynamics during feeding.

PMID- 24744035
TI  - Yeast metabolomics: sample preparation for a GC/MS-based analysis.
AB  - Metabolome sample preparation is one of the key factors in metabolomics analyses.
      The quality of the metabolome data will depend on the suitability of the
      experimental procedures to the cellular system (e.g., yeast cells) and the
      analytical performance. Here, we summarize a protocol for metabolome analysis of
      yeast cells using gas chromatography-mass spectrometry (GC-MS). First, the main
      phases of a metabolomics analysis are identified: sample preparation, metabolite
      extraction, and analysis. We also provide an overview on different methods used
      to quench samples and extract intracellular metabolites from yeast cells. This
      protocol provides a detailed description of a GC-MS-based analysis of yeast
      metabolome, in particular for metabolites containing amino and/or carboxyl
      groups, which represent most of the compounds participating in the central carbon
      metabolism. 

PMID- 24744036
TI  - 13C-based metabolic flux analysis in yeast: the Pichia pastoris case.
AB  - Metabolic flux analysis based on tracing patterns of stable isotopes,
      particularly (13)C, comprises a set of methodologies to experimentally quantify
      intracellular biochemical reaction rates, i.e., to measure carbon flux
      distributions through a metabolic network. This allows quantifying the response
      of a metabolic network to an environmental or genetic perturbation (i.e., the
      metabolic phenotype). Here, we describe a protocol based on growing yeast on a
      (13)C-labelled substrate and subsequent NMR detection of (13)C-patterns in
      proteinogenic amino acids. To calculate metabolic fluxes, we describe two
      complementary mathematical approaches using available software; namely, an
      approach based on the estimation of local ratios in network nodes, and a method
      based on a global iterative fitting approach. Furthermore, we consider
      specificities of these protocols for their application to the yeast Pichia
      pastoris growing on multicarbon substrates other than glucose (glycerol), as well
      as the case when methanol is used as co-substrate in combination with glucose or
      glycerol. 

PMID- 24744037
TI  - Pathway Activity Profiling (PAPi): a tool for metabolic pathway analysis.
AB  - Pathway Activity Profiling (PAPi) is a method developed to correlate levels of
      metabolites to the activity of metabolic pathways operating within biological
      systems. Based solely on a metabolomics data set and the Kyoto Encyclopedia of
      Genes and Genomes, PAPi predicts and compares the activity of metabolic pathways
      across experimental conditions, which considerably improves the hypothesis
      generation process for achieving the biological interpretation of biological
      studies. In this chapter, we describe how to apply PAPi to a metabolomics data
      set using the R-software. 

PMID- 24744038
TI  - QTL mapping by pooled-segregant whole-genome sequencing in yeast.
AB  - Quantitative trait locus (QTL) mapping by pooled-segregant whole-genome
      sequencing in yeast is a robust methodology for the simultaneous identification
      of superior genes involved in polygenic traits (e.g., high ethanol tolerance). By
      crossing two haploid strains with opposite phenotypes, being one of interest, the
      resulting diploid is sporulated, the meiotic segregants phenotyped, and a pool of
      selected segregants with the phenotype of interest assembled. The genotyping by
      pooled-segregant sequencing constitutes a fast and reliable methodology to map
      all QTL defining the trait of interest. The QTLs can be further analyzed by
      reciprocal hemizygosity analysis to identify the causative superior alleles that
      can subsequently be used for yeast strain improvement by targeted genetic
      engineering. 

PMID- 24744039
TI  - Genome-scale metabolic models of yeast, methods for their reconstruction, and
      other applications.
AB  - Here, we present the concept of genome-scale metabolic models and some of their
      applications in metabolic engineering of yeast and in the analysis of gene
      expression data. The yeast species for which there are available genome-scale
      metabolic models are reviewed, as well as the methods for the reconstruction of
      genome-scale metabolic models for new species. Some commonly used algorithms for
      metabolic engineering and data integration are described. 

PMID- 24744040
TI  - Model-guided identification of gene deletion targets for metabolic engineering in
      Saccharomyces cerevisiae.
AB  - Identification of metabolic engineering strategies for rerouting intracellular
      fluxes towards a desired product is often a challenging task owing to the
      topological and regulatory complexity of metabolic networks. Genome-scale
      metabolic models help tackling this complexity through systematic consideration
      of mass balance and reaction directionality constraints over the entire network.
      Here, we describe how genome-scale metabolic models can be used for identifying
      gene deletion targets leading to increased production of the desired product.
      Vanillin production in Saccharomyces cerevisiae is used as a case study
      throughout this chapter. 

PMID- 24744041
TI  - Patents: a tool to bring innovation from the lab bench to the marketplace.
AB  - Intellectual property (IP) is creations of the mind. Protecting IP through
      patents is an important venue for a researcher to reap rewards from his
      scientific endeavors. It is part of a competitive strategy for bringing one's
      invention to the marketplace. Using the US and European patent systems as
      examples, we provide here an overview of how patents protect innovation, with a
      focus on biotechnology. We explain what a patent is, what a patent owner can do
      with a patent, and how patents are granted. The article ends with some recent
      examples of noteworthy patents in the field of yeast research. 

PMID- 24744042
TI  - Perceived barriers to primary care among western Canadians with chronic
      conditions.
AB  - BACKGROUND: This analysis explores barriers to the receipt of health care from a
      primary care physician for management of chronic conditions. DATA AND METHODS: A
      population-based survey was administered to adults in Manitoba, Saskatchewan,
      Alberta and British Columbia who had hypertension, diabetes, heart disease or
      stroke (n=1,849). Associations between socio-demographic factors and barriers to
      receipt of primary care were identified. RESULTS: Most respondents with chronic
      conditions required care from a primary care physician in the past year and had
      no difficulty receiving it; about 10% reported a barrier. Barriers were most
      commonly reported by respondents with diabetes (16%) and were related to
      initiation of care or waiting too long to get care. INTERPRETATION: A small
      percentage of adults with chronic conditions report barriers to receiving care
      from a primary care physician.

PMID- 24744043
TI  - Trends in out-of-pocket health care expenditures in Canada, by household income,
      1997 to 2009.
AB  - BACKGROUND: Canadian households are spending an increasing share of their
      household income on health care not covered by public plans. This study
      investigates trends in out-of-pocket expenditures for health care services and
      products by household income quintile from 1997 to 2009. DATA AND METHODS:
      Biennial estimates from the Survey of Household Spending between 1997 and 2009
      were used to examine changes in out-of-pocket health care expenditures, by
      household income quintile. The statistical significance of these changes was
      assessed using linear and logistic regression. RESULTS: In 2009, the percentage
      of after-tax household income spent on health care among low-income households
      (5.7%) was nearly twice that of high-income households (2.6%). Approximately 40%
      of households in the two lowest income quintiles spent more than 5% of their
      total after-tax income on health care services and products, compared with 14% of
      households in the highest income quintile. The increase in spending between 1997
      and 2009 was greatest for households in the lowest income quintile (63%).
      INTERPRETATION: Out-of-pocket health care expenditures have increased for
      households in all income quintiles, but the relative increase was greatest among
      households in lower income quintiles.

PMID- 24744044
TI  - Hiding in plain sight: cuticular compound profile matching conceals a larval
      tortoise beetle in its host chemical cloud.
AB  - Larvae of tortoise beetles are postulated to have fecal shields as the main
      defensive strategy against predators. Such a device protects beetles both
      physically and chemically. In order to examine how larvae Chelymorpha reimoseri
      are protected against predatory ants, which frequently visit extrafloral
      nectaries in their host plant, the morning glory Ipomoea carnea, we conducted
      anti-predation bioassays with live 5th instars. In the field, larvae in contact
      with ants had survival between 40 and 73 %, independently of shield presence. In
      the laboratory, when exposed to Camponotus crassus, larvae with shields had
      significantly higher survival (85 %) than those without shields (64 %). In both
      scenarios, larval survival was significantly higher when compared with palatable
      Spodoptera frugiperda larvae, as the latter were all consumed. We also observed
      that when C. reimoseri larvae showed no movement, the ants walked on them without
      attacking. We hypothesized that if the larval integument has a pattern of
      cuticular compounds (CCs) similar to that of its host plant, larvae would be
      rendered chemically camouflaged. In the field and laboratory, the freeze-dried
      palatable larvae of S. frugiperda treated with CCs of 5th instar C. reimoseri and
      left on I. carnea leaves were significantly less removed by ants than controls
      without these compounds. We also found a similarity of approximately 50 % between
      the CCs in C. reimoseri larvae and I. carnea host leaves. Both findings provide
      evidence in support of the hypothesis that chemical camouflage plays an important
      role in larval defense, which is reported for the first time in an ectophagous
      leaf beetle larva. 

PMID- 24744045
TI  - Early and delayed prediction of axillary lymph node neoadjuvant response by (18)F
      FDG PET/CT in patients with locally advanced breast cancer.
AB  - PURPOSE: To determine the utility of (18)F-FDG (FDG) PET/CT performed in an early
      and delayed phase during neoadjuvant chemotherapy in the prediction of lymph node
      histopathological response in patients with locally advanced breast cancer.
      METHODS: FDG PET/CT studies performed in 76 patients (mean age 53 years) at
      baseline (PET-1), after the second course of chemotherapy (PET-2) and after the
      last course of chemotherapy (PET-3) were prospectively analysed. Inclusion
      criteria were lymph node involvement detected by PET/CT and non-sentinel node
      biopsy before or after the baseline PET/CT scan. Following the recommendations of
      the 12th International Breast Conference (St. Gallen), the patients were divided
      into five subgroups in relation to biological prognostic factors by
      immunohistochemistry. For diagnosis visual and semiquantitative analyses was
      performed. Absence of detectable lymph node uptake on the PET-2 or PET-3 scan
      with respect to the PET-1 scan was considered metabolic complete response (mCR).
      Lymph nodes were histopathologically classified according the lymph node
      regression grade and in response groups as pathological complete response (pCR)
      or not pCR (type A/D or B/C of the Smith grading system, respectively). ROC
      analysis was performed to determine a cut-off value of Delta% SUV1-2 and SUV1-3
      for prediction of nodal status after chemotherapy. An association between mCR and
      pCR was found (Cohen's kappa analysis), and associations between phenotypes and
      metabolic behaviour and the final histopathological status were also found.
      RESULTS: Lymph node pCR was seen in 34 patients. The sensitivity, specificity,
      and positive and negative predictive values of PET-2 and PET-3 in establishing
      the final status of the axilla after chemotherapy were 52 %, 45 %, 50 % and 47 %,
      and 33 %, 84 %, 67 % and 56 %, respectively. No significant relationship was
      observed between mCR on PET-2 and PET-3 and pCR (p = 0.31 and 0.99,
      respectively). Lymph node metabolism on PET-1 was not able to predict the final
      histopathological status, whereas basal carcinomas showed a higher rate of pCR
      (70.6 %) than the other groups (p = 0.03). CONCLUSION: FDG PET/CT seems to have
      limitations in both the early and delayed evaluation of lymph node status after
      chemotherapy, with reduced predictive values.

PMID- 24744046
TI  - Formation of elongated fascicle-inspired 3D tissues consisting of high-density,
      aligned cells using sacrificial outer molding.
AB  - The majority of muscles, nerves, and tendons are composed of fiber-like fascicle
      morphology. Each fascicle has a) elongated cells highly aligned with the length
      of the construct, b) a high volumetric cell density, and c) a high length-to
      width ratio with a diameter small enough to facilitate perfusion. Fiber-like
      fascicles are important building blocks for forming tissues of various sizes and
      cross-sectional shapes, yet no effective technology is currently available for
      producing long and thin fascicle-like constructs with aligned, high-density
      cells. Here we present a method for molding cell-laden hydrogels that generate
      cylindrical tissue structures that are ~100 MUm in diameter with an extremely
      high length to diameter ratio (>100 : 1). Using this method we have successfully
      created skeletal muscle tissue with a high volumetric density (~50%) and perfect
      cell alignment along the axis. A new molding technique, sacrificial outer
      molding, allows us to i) create a long and thin cylindrical cavity of the desired
      size in a sacrificial mold that is solid at a low temperature, ii) release
      gelling agents from the sacrificial mold material after the cell-laden hydrogel
      is injected into fiber cavities, iii) generate a uniform axial tension between
      anchor points at both ends that promotes cell alignment and maturation, and iv)
      perfuse the tissue effectively by exposing it to media after melting the
      sacrificial outer mold at 37  degrees C. The effects of key parameters and
      conditions, including initial cavity diameter, axial tension, and concentrations
      of the hydrogel and gelling agent upon tissue compaction, volumetric cell
      density, and cell alignment are presented.

PMID- 24744047
TI  - Protective effect of INI-0602, a gap junction inhibitor, on dopaminergic
      neurodegeneration of mice with unilateral 6-hydroxydopamine injection.
AB  - INI-0602, a novel gap junction hemichannel inhibitor, was administered to hemi
      Parkinsonism mice generated by striatal 6-hydroxydopamine injection. INI-0602
      prevented the toxic activation of microglia, such as the increased number of the
      activated form, enlargement of cell bodies and induction of proinflammatory
      cytokines, such as IL-1beta and TNFalpha, in the ipsilateral striatum. On the
      other hand, INI-0602 induced the expression of neurotrophic factors, such as
      brain-derived neurotrophic factor and NT-4/5, in the 6-hydroxydopamine-treated
      striatum. INI-0602 treatment blocked not only dopaminergic loss in both the
      striatum and substantia nigra, but also apomorphine-induced rotational behavior. 

PMID- 24744048
TI  - Quantitative evaluation of electroconvulsive therapy for Parkinson's disease with
      refractory psychiatric symptoms.
AB  - Patients with advanced-stage Parkinson's disease (PD) occasionally experience
      refractory depression or catatonic stupor. Electroconvulsive therapy (ECT) has
      been reported as a successful procedure for both severe psychosis and motor
      symptoms in patients with PD. Four patients with PD who were receiving ECT were
      quantitatively evaluated using the Unified PD Rating scale part III, Hoehn and
      Yahr scale, Barthel index, Neuropsychiatric Inventory, mini-mental state
      examination, Revised Hasegawa's Dementia scale, Beck's Depression Inventory, and
      Hamilton Rating Scale for Depression-17. We adopted the "half-age" method, which
      is an age-based stimulus-dosing method. The patients showed improvement in
      symptoms of psychosis and motor symptoms without any adverse effects. The
      interval of improvement after ECT varied among patients. Of note, a decrease in
      psychiatric symptoms successfully alleviated the burden of caregivers. ECT may be
      useful to treat parkinsonism with refractory psychosis, major depression, or
      catatonic stupor, within the limitations of the patients enrolled. 

PMID- 24744049
TI  - Cross-cultural aspects of anxiety disorders.
AB  - A person's cultural background influences the experience and expression of
      emotions. In reviewing the recent literature on cross-cultural aspects of anxiety
      disorders, we identified some culturally related ethnopsychology/ethnophysiology
      factors (the culture's conceptualizations of how the mind and body function) and
      contextual factors that influence anxiety disorders.
      Ethnopsychology/ethnophysiology factors include the person's ideas about the
      mental and bodily processes (and their interaction), whereas contextual factors
      are associated with the social norms and rules that may contribute to anxiety,
      including individualism vs. collectivism and self-construals. From the
      perspective of ethnopsychology/ethnophysiology and contextual factors, we will
      discuss "khyal cap" ("wind attacks"), taijin kyofusho, and ataques de nervios,
      three prominent examples of culture-specific expressions of anxiety disorders
      that have all been included in the DSM-5 list of cultural concepts of distress. 

PMID- 24744050
TI  - Combined effects of body composition and ageing on joint torque, muscle
      activation and co-contraction in sedentary women.
AB  - This study aimed to establish the interplay between body mass, adiposity, ageing
      and determinants of skeletal muscle strength. One hundred and two untrained
      healthy women categorised by age into young (Y) (mean +/- SD, 26.7 +/- 9.4 years)
      vs. old (O) (65.1 +/- 7.2 years) were assessed for body fat, lean mass, plantar
      flexion and dorsiflexion maximum voluntary isometric contraction (MVC) torque,
      muscle activation capacity and antagonist muscle co-contraction. MVC torque
      normalised to body mass in the obese group was 35 and 29 % lower (p < 0.05) in Y
      and 34 and 31 % lower (p < 0.05) in O, compared with underweight and normal
      weight individuals, respectively. Y with >=40 % body fat had significantly lower
      activation than Y with <40 % body fat (88.3 vs. 94.4 %, p < 0.05), but O did not
      exhibit this effect. Co-contraction was affected by ageing (16.1 % in O vs. 13.8
      % in Y, p < 0.05) but not body composition. There were significant associations
      between markers of body composition, age, strength and activation capacity, with
      the strongest correlation between muscle strength and total body mass (r (2) =
      0.508 in Y, p < 0.001, vs. r (2) = 0.204 in O, p < 0.01). Furthermore, the age
      related loss in plantar flexion (PF) MVC torque was exacerbated in obese compared
      to underweight, normal weight and overweight individuals (-0.96 vs. -0.54, -0.57
      and -0.57 % per year, p < 0.05). The negative impact of adiposity on muscle
      performance is associated with not only muscular but also neural factors.
      Overall, the effects of ageing and obesity on this system are somewhat
      cumulative.

PMID- 24744051
TI  - IL-2/CD40-activated macrophages rescue age and tumor-induced T cell dysfunction
      in elderly mice.
AB  - The role of macrophages and their interactions with T cells during aging is not
      well understood. We determined if activating elderly-derived macrophages could
      rescue age-related and tumor-induced T cell dysfunction. Healthy elderly (18-24
      months) Balb/c contained significantly more splenic IL-10-secreting M2
      macrophages and myeloid-derived suppressor cells than young (6-8 weeks) mice.
      Exposure to syngeneic mesothelioma or lung carcinoma-conditioned media polarized
      peritoneal macrophages into suppressive M2-macrophages regardless of age. Tumor
      exposed, elderly, but not young-derived, macrophages produced high levels of IL-4
      and could not induce T cell IFN-gamma production. We attempted to rescue tumor
      exposed macrophages with LPS/IFN-gamma (M1 stimulus) or IL-2/agonist anti-CD40
      antibody. Tumor-exposed, M1-stimulated macrophages retained high CD40 expression,
      yet TNF-alpha and IFN-gamma production were diminished relative to non-tumor
      exposed, M1-stimulated controls. These macrophages induced young and elderly
      derived T cell proliferation however, T cells did not secrete IFN-gamma. In
      contrast, tumor-exposed, IL-2/CD40-stimulated macrophages rescued elderly-derived
      T cell IFN-gamma production, suggesting that IL-2/CD40-activated macrophages
      could rescue T cell immunity in aging hosts. 

PMID- 24744052
TI  - Implementation of independent nurse prescribing in UK mental health settings:
      focus on attention-deficit/hyperactivity disorder.
AB  - Legislative changes that came into effect in the UK in April 2012 gave nurse
      independent prescribers (NIPs) the power to prescribe schedule 2-5 controlled
      drugs. Therefore, suitably qualified UK nurses can now independently prescribe
      any drug for any medical condition within their clinical competence. The
      potential benefits of independent nurse prescribing include improved access to
      medications and more efficient use of skills within the National Health Service
      workforce. This review explores the published literature (to July 2013) to
      investigate whether the predicted benefits of NIPs in mental health settings can
      be supported by empirical evidence, with a specific focus on nurse-led management
      of patients with attention-deficit/hyperactivity disorder (ADHD). The most common
      pharmacological treatments for ADHD are controlled drugs. Therefore, the 2012
      legislative changes allow nurse-led ADHD services to offer holistic packages of
      care for patients. Evidence suggests that independent prescribing by UK nurses is
      safe, clinically appropriate and associated with high levels of patient
      satisfaction. The quality of the nurse-patient relationship and nurses' ability
      to provide flexible follow-up services suggests that nurse-led ADHD services are
      well positioned to enhance the outcomes for patients and their parents/carers.
      However, the empirical evidence available to support the value of NIPs in mental
      health settings is limited. There is a need for additional high-quality data to
      verify scientifically the value of nurse-delivered ADHD care. This evidence will
      be invaluable in supporting the growth of nurse-led ADHD services and for those
      who support greater remuneration for the expanded role of NIPs. 

PMID- 24744053
TI  - Amniotic fluid-derived mesenchymal stem cells: characteristics and therapeutic
      applications.
AB  - PURPOSE: Amniotic fluid mesenchymal stem cells (AF-MSCs) are promising candidates
      for cell-based therapy. This review presents a comprehensive overview of the
      features and therapeutic applications of these cells. METHODS: This is a
      literature review combined with experience of practice. CONCLUSION: Although the
      long-term risks of AF-MSCs require further investigation, these cells are
      increasing in popularity in the fields of regenerative medicine and targeting
      therapy because of their unique properties.

PMID- 24744055
TI  - Benign schwannoma in supraclavicular region: a false-positive lymph node
      recurrence of breast cancer suspected by PET scan.
AB  - INTRODUCTION: Positron emission tomography (PET) is the most accurate imaging
      modalities to detect malignancies. And it helps to take decisions regarding
      diagnosis, staging, recurrence, and therapeutical management. CASE PRESENTATION:
      We report a case of a suspected supraclavicular lymph node relapse, diagnosed by
      PET-CT in a breast cancer patient. The lymph node was surgically removed in
      outpatient with local anesthesia. Histological findings diagnosed a benign
      Schwannoma. In this patient PET-CT failed to distinguish benign tumors from
      metastatic supraclavicular lymph nodes. CONCLUSION: This case confirms the need
      to investigate histologically suspected supraclavicular lesions, during breast
      cancer follow up.

PMID- 24744054
TI  - Worldwide survey of IVF practices: trigger, retrieval and embryo transfer
      techniques.
AB  - PURPOSE: To identify common and varying practice patterns used by in vitro
      fertilization (IVF) providers from a broadly distributed, worldwide survey.
      Specific information regarding clinical IVF practices involving the oocyte
      maturation triggering, oocyte retrieval and embryo transfer was elicited.
      METHODS: This is an internet-based questionnaire study of IVF practices
      throughout the world. We used 26 multiple choice questions regarding common
      clinical practices. The data reported are weighted based on the number of IVF
      cycles performed at the specific IVF center, represented by a single respondent.
      RESULTS: Surveys were completed from 359 centers in 71 countries throughout the
      world. The most common practice patterns (defined as >=75 % of IVF cycles)
      identified included: use of human chorionic gonadotropin (hCG) for trigger with
      an antagonist protocol, no routine patient monitoring from hCG trigger to oocyte
      retrieval, timing oocyte retrieval 34-37 h following oocyte maturing trigger, use
      of a single lumen retrieval needle, no routine tests following oocyte retrieval
      prior to patient discharge and use of ultrasound assistance with embryo transfer.
      CONCLUSIONS: This is the largest and most diversely represented survey of
      specific IVF practices addressing oocyte maturation triggers, oocyte retrieval
      and embryo transfers. Several uniform practice patterns were identified that can
      be correlated with evidence-based medicine; however, we identified multiple
      variable practice patterns which is likely the result of the absence of
      definitive evidence to guide IVF practitioners. The results of this survey allow
      IVF providers to compare their specific practice patterns with those of a global
      diverse population of IVF providers.

PMID- 24744056
TI  - The experiences and perceptions of family planning of female Chinese asylum
      seekers living in the UK.
AB  - INTRODUCTION: Chinese family planning policy is unique. There is limited sex
      education and the state is highly influential. This has resulted in extremely
      wide coverage of contraception with long-acting methods being favoured. The
      Chinese constitute a large proportion of asylum applicants to the UK. This study
      examines how their experiences and decisions about family planning in the UK are
      shaped by their cultural background. METHODS: Data were drawn from 10 semi
      structured qualitative interviews with female Chinese asylum seekers recruited
      through a family planning clinic in the UK. RESULTS: The increased autonomy
      provided by the UK system was appreciated by the participants. Choice of
      contraceptive method was influenced by traditional cultural beliefs and values,
      and the effect of hormonal contraception on menstruation was particularly
      concerning. Women arrived from China with little knowledge of contraception.
      Friends from a similar background were the most trusted source of advice. When
      transitioning from China to the UK unwanted pregnancies had occurred amongst
      unmarried women who had missed out on sex education while living in China.
      CONCLUSIONS: Chinese societal and cultural practices continue to influence family
      planning decisions made within the UK. Culturally competent health strategies are
      needed to ensure Chinese immigrant women fully benefit from family planning
      within the UK.

PMID- 24744057
TI  - Evolution of symbiosis with resource allocation from fecundity to survival.
AB  - Symbiosis is one of the most fundamental relationships between or among organisms
      and includes parasitism (which has negative effects on the fitness of the
      interacting partner), commensalism (no effect), and mutualism (positive effects).
      The effects of these interactions are usually assumed to influence a single
      component of a species' fitness, either survival or fecundity, even though in
      reality the interaction can simultaneously affect both of these components. I
      used a dual lattice model to investigate the process of evolution of mutualistic
      symbiosis in the presence of interactive effects on both survival and fecundity.
      I demonstrate that a positive effect on survival and a negative effect on
      fecundity are key to the establishment of mutualism. Furthermore, both the
      parasitic and the mutualistic behaviour must carry large costs for mutualism to
      evolve. This helps develop a new understanding of symbiosis as a function of
      resource allocation, in which resources are shifted from fecundity to survival.
      The simultaneous establishment of mutualism from parasitism never occurs in two
      species, but can do so in one of the species as long as the partner still behaves
      parasitically. This suggests that one of the altruistic behaviours in a
      mutualistic unit consisting of two species must originate as a parasitic
      behaviour.

PMID- 24744058
TI  - Ricoseius loxocheles, a phytoseiid mite that feeds on coffee leaf rust.
AB  - One of the most important diseases of coffee plants is the coffee leaf rust
      fungus Hemileia vastatrix Berkeley and Broome (Uredinales). It can cause 30 %
      yield loss in some varieties of Coffea arabica (L.). Besides fungus, the coffee
      plants are attacked by phytophagous mites. The most common species is the coffee
      red mite, Oligonychus ilicis McGregor (Acari: Tetranychidae). Predatory mites of
      the Phytoseiidae family are well-known for their potential to control herbivorous
      mites and insects, but they can also develop and reproduce on various other food
      sources, such as plant pathogenic fungi. In a field survey, we found Ricoseius
      loxocheles (De Leon) (Acari: Phytoseiidae) on the necrotic areas caused by the
      coffee leaf rust fungus during the reproductive phase of the pathogen. We
      therefore assessed the development, survivorship and reproduction of R.
      loxocheles feeding on coffee leaf rust fungus and measured predation and
      oviposition of this phytoseiid having coffee red mite as prey under laboratory
      conditions. The mite fed, survived, developed and reproduced successfully on this
      pathogen but it was not able to prey on O. ilicis. Survival and oviposition with
      only prey were the same as without food. This phytoseiid mite does not really use
      O. ilicis as food. It is suggested that R. loxocheles is one phytoseiid that uses
      fungi as a main food source. 

PMID- 24744059
TI  - Trends over time and regional variations in the rate of laser trabeculoplasty in
      the Medicare population.
AB  - IMPORTANCE: Laser trabeculoplasty (LTP) is routinely used to treat open-angle
      glaucoma; hence, understanding variations in its use over time and region is
      important. OBJECTIVE: To determine trends over time and the regional variation in
      the performance of LTP. DESIGN, SETTING, AND PARTICIPANTS: Database analysis of a
      5% random sample of all Medicare beneficiaries 65 years or older with continuous
      Part B (medical insurance) coverage and no enrollment in a health maintenance
      organization for each year from 2002 through 2009. INTERVENTIONS: We counted
      unique claims with a Current Procedural Terminology code of 65855 (LTP) submitted
      by ophthalmologists, optometrists, ambulatory surgery centers, or outpatient
      hospitals by region for each year. We examined trends over time and regional
      variation in LTP rates in 9 large geographic regions. MAIN OUTCOMES AND MEASURES:
      Rate of LTP per 10,000 Medicare beneficiary person-years and per 10,000 diagnosed
      open-angle glaucoma (OAG) person-years. RESULTS: The LTP rates per 10,000
      Medicare beneficiary person-years were 36.3, 60.1, and 53.5 for 2002, 2006, and
      2009, respectively. The 65.6% increase between 2002 and 2006 and the 11.0%
      decrease between 2006 and 2009 were statistically significant (tests for linear
      trend, P = .009 and P < .001, respectively). Similarly, the LTP rate among
      Medicare beneficiaries with OAG increased from 507.9 per 10,000 person-years in
      2002 to 824.3 per 10,000 person-years in 2006 (62.3% increase; P = .009) and then
      decreased to 741 per 10,000 person-years by 2009 (10.1% decrease; P = .004). The
      rates per 10,000 OAG person-years differed significantly by region, ranging from
      314 in the East South-Central region to 607 in the East North-Central region in
      2002 (93.2% higher; P < .001). A similar range of variation was observed in
      subsequent years. CONCLUSIONS AND RELEVANCE: The rate of LTP for Medicare
      patients with OAG peaked in 2006 and then decreased through 2009. Nearly twice as
      many LTP procedures per Medicare beneficiary were performed in some regions
      compared with others throughout the period.

PMID- 24744060
TI  - A chicken embryo model for the study of umbilical and supraumbilical body wall
      malformations.
AB  - BACKGROUND/PURPOSE; The embryology of ventral body wall malformations is only
      partially understood, although their incidence is relatively common. As only few
      experimental data exist on the development of those defects, the aim of our study
      was to compare the teratogenic effect of trypan blue (TB) and suramin (SA) in
      their capability to induce umbilical and supraumbilical abdominal wall
      malformations in a chicken egg model. MATERIALS AND METHODS: A total of 255
      fertilized chicken eggs were incubated at 38  degrees C and 75% relative
      humidity. Embryos were treated in ovo on incubation day 2.5 (Hamburger/Hamilton
      (HH) stage 13). The eggshell was windowed, and solutions of TB or SA were
      injected into the coelomic cavity at the region of the umbilicus. The window was
      closed and the embryos reincubated until examination on day 8 (HH 34). RESULTS: A
      total of 60 embryos survived in each group. The largest number of embryos
      presented with defects in the umbilical and supraumbilical region (25% in the SA
      group and 40% in the TB group). A combination of both defects
      (thoracoabdominoschisis) was seen in 20% of the TB and 8.3% of the SA groups,
      respectively. Associated anomalies found in both groups were head and eye
      defects, abnormal pelvic configurations, leg deformities, and mild forms of
      cloacal exstrophies. CONCLUSIONS: TB and SA have both a high potential to induce
      umbilical and supraumbilical ventral body wall malformations in chicken embryos.
      This novel animal model might help to establish a more profound understanding of
      the developmental steps in ventral body wall formation and the embryology for its
      malformations.

PMID- 24744062
TI  - Choroidoretinal granuloma in a young female patient.
AB  - A 16-year-old Brazilian female patient presented with blurring of vision in the
      right eye. Corrected visual acuity was OD 2/20, OS 20/20. Afferent pupillary
      defect was absent and anterior segment examination revealed anterior uveitis.
      Fundus examination showed light vitritis and a raised grey-white granuloma
      located at posterior pole with focal serous retinal detachment on optical
      coherence. Indocyacnine green angiography disclosed a complete mask effect in
      granuloma's area. Differential diagnoses were infectious (bacterial, viral,
      fungal and parasites) diseases, systemic inflammatory diseases, tumours. Blood
      serologies (HIV, toxoplasma, Borrelia, cytomegalovirus (CMV), herpes simplex
      virus (HSV), varicella-zoster virus (VZV), rubeola) showed positive results for
      IgM and IgG for toxoplasma, and anterior chamber tap (PCR for toxoplasma, CMV,
      HSV, VZV) revealed toxoplasma DNA. Anti-toxoplasma therapy, pyrimethamine,
      sulfadiazine and calcium folinate, was administered immediately. On follow-up
      granuloma regression was observed, with complete visual restoration. This case
      demonstrates a clinically challenging posterior pole granuloma.

PMID- 24744061
TI  - Friend or foe? Figuring out the difference between FPIES, IgE-mediated allergy
      and food intolerance.
AB  - Most physicians recognise the severe nature of the anaphylactic reactions
      associated with IgE-mediated food allergy. Adverse reactions to food involving
      non-IgE mechanisms are often less well understood and are often not diagnosed.
      Food protein-induced enterocolitis syndrome (FPIES) is an example of a severe non
      IgE immune-mediated food reaction that is part of a spectrum of what is believed
      to be T-cell-mediated reactions. FPIES results in excessive emesis and diarrhoea
      hours after ingestion of the offending food. While common triggers include milk,
      soy, wheat and oat, some children may have multiple triggers, leading to
      malnutrition from lack of food options and unusual developmental concerns related
      to food aversion. 

PMID- 24744063
TI  - Solid pseudopapillary tumour of pancreas.
AB  - Solid pseudopapillary tumour of the pancreas is a rare neoplasm (1%). This tumour
      primarily affects young women and is usually treated with surgical resection with
      a relatively favourable prognosis. We report an 18-year-old female patient
      presenting with moderate grade abdominal pain for 5 weeks. Abdominal examination
      revealed a lump palpable in the right upper abdomen. Contrast-enhanced CT abdomen
      reported soft tissue lesion arising from uncinate process of pancreas causing
      adjacent compression. Endoscopic ultrasound-guided fine-needle aspiration biopsy
      yielded a cellular sample comprising pseudopapillary arrangement with bland
      appearing tumour cells consistent with benign neoplasm. And because of unusual
      location, Whipple procedure was performed. The patient was discharged under
      satisfactory conditions. Final histology confirmed the diagnosis. Solid
      pseudopapillary tumours of the pancreas are a rare but treatable pancreatic
      tumour. Complete surgical excision is the treatment of choice and can be achieved
      through an open or minimal access technique. 

PMID- 24744064
TI  - Solar urticaria in a 1-year-old infant: diagnosis and management.
AB  - Solar urticaria is a type of inducible urticaria triggered by sun exposure
      resulting in hives on exposed skin as well as risk of developing systemic
      symptoms. Most cases are reported in the adult population. However, cases do
      occur in children. We present a case of visible light induced urticaria in a 12
      month-old girl that demonstrates the need for accurate diagnosis and appropriate
      management. 

PMID- 24744065
TI  - Paget's disease: a unique case snippet.

PMID- 24744066
TI  - 'Rice bodies in the knee': classic tuberculosis of the knee.

PMID- 24744067
TI  - Simultaneous discovery of bifrontal meningiomas and a glioblastoma multiforme.

PMID- 24744068
TI  - Clinicoradiological improvement of intracranial tubercular abscess with medical
      management alone.
AB  - Tubercular abscess is a rare presentation of central nervous system tuberculosis
      (TB), which commonly presents as tuberculoma or meningitis. Most of the published
      cases of tubercular brain abscess have been dealt with by surgical treatment
      along with medical management. We here report a case of intracranial tubercular
      abscess in a 17-year-old girl presenting with fever, headache and right
      hemiparesis who showed significant clinicoradiological improvement with medical
      management alone. Thus, in a country like India where TB is highly endemic, TB
      should be considered as a possible aetiology for any intracranial lesion with
      radiological appearance suggestive of an abscess and surgical treatment can be
      kept as an option in case of neurological deficits, hydrocephalus or treatment
      failure. 

PMID- 24744069
TI  - Extensive warfarin-induced skin necrosis successfully treated with negative
      pressure wound therapy.
AB  - A 55-year-old woman presented with an extensive warfarin-induced skin necrosis
      while an inpatient for treatment of a pulmonary embolism and thromboembolic
      stroke. She had a background of diabetes mellitus, hypertension and
      dyslipidaemia. Her warfarin was stopped and she was anticoagulated with low
      molecular weight heparin. The wound was successfully treated with a combination
      of antibiotic, debridement and negative pressure wound therapy. 

PMID- 24744070
TI  - Acute bilateral glaucoma and panuveitis as a side effect of topiramate for weight
      loss treatment.
AB  - A 54-year-old male patient presented to our clinic with acute angle-closure
      glaucoma and panuveitis in both eyes after being treated with topiramate for
      binge eating and obesity. This case report emphasises the hazardous side effects
      of treatment with topiramate with unusual indication and the precaution a
      caretaker must take when treating a patient. 

PMID- 24744071
TI  - Misidentification of Mycobacterium fortuitum in an immunocompetent patient
      presenting with a unilateral neck mass.
AB  - A 31-year-old African man with a blameless medical history presented with an
      enlarging neck swelling of 6 months duration. He was systemically well with
      normal heamatobiochemistry. MRI of the neck demonstrated abnormal signalling in
      the subcutaneous fat overlying the posterior spinal muscles in the midline and
      the left sternocleidomastoid muscle. Scanty growth of Rhodococcus equi was
      reported from a turbid fine needle aspirate of the neck on two separate
      occasions. The swelling progressed despite numerous antibiotic combinations which
      necessitated surgical debridement. Analysis of debrided tissue using 16S rDNA
      surprisingly identified Mycobacterium fortuitum, not R equi, thereby resolving
      our diagnostic conundrum. 

PMID- 24744072
TI  - Pulmonary arteriovenous malformation: a rare cause of dyspnoea on exertion.

PMID- 24744073
TI  - Paranasal sinus and retro-orbital metastasis in a case of breast carcinoma: a
      clinicoradiological review.
AB  - Metastatic spread from non-head and neck tumours (H&N) to the paranasal and
      orbital region is extremely rare. We present a case of breast cancer metastasis
      to the left sphenoid wing, lateral wall left orbit, lateral wall left sphenoid
      sinus, medial and lateral wall left maxillary sinus and left pterygoid plates. We
      provide an exhaustive clinicoradiological imaging with a brief literature review.

PMID- 24744074
TI  - Lateral foot pain following open reduction and internal fixation of the fracture
      of the fifth metatarsal tubercle: treated by arthroscopic arthrolysis and
      endoscopic tenolysis.
AB  - We report a case of fracture of the tuberosity of the fifth metatarsal which was
      managed by tension band wiring and bone grafting. It was complicated by
      symptomatic fibrosis of the operated site involving the cubometatarsal joint,
      peroneus brevis tendon, peroneus tertius tendon and the long extensor tendon to
      the fifth toe. This was successfully managed by arthroscopic lysis of the
      involved joint and tendons. 

PMID- 24744075
TI  - Myasthenia gravis masquerading as dysphagia: unveiled by magnesium infusion.
AB  - Myasthenia gravis (MG) is a neuromuscular disorder that typically affects the
      ocular, bulbar, neck, proximal limbs and respiratory muscles. Dysphagia can
      occasionally be the only presenting symptom leading to extensive but ultimately
      futile gastrointestinal workup. Delay in diagnosis and use of certain
      pharmacological agents in the interim can lead to a myasthenic crisis, which
      though diagnostic is life threatening. We document a case of dysphagia as the
      only symptom of myasthenia, diagnosed after a magnesium infusion precipitated
      myasthenic crisis. A 70-year-old Caucasian woman who had had progressive
      dysphagia for 2 years, for which multiple oesophageal dilations were performed.
      During a hosptalisation for further gastrointestinal workup, she went into
      myasthenic crisis (respiratory failure) after receiving magnesium replacement.
      She required ventilatory support and received five plasma exchange (PLEX)
      treatments after myasthenia was confirmed by the detection of high
      antiacetylcholine receptor antibody. Though her symptoms improved, she had a
      prolonged hospital stay (25 days) and required 18 days of mechanical ventilation.
      This underscores the morbidity associated with a delay in diagnosis of this
      condition. This case report suggests that neuromuscular causes should be
      considered early in elderly patients presenting with dysphagia. Timely diagnosis,
      initiation of management and avoidance of drugs that affect neuromuscular
      transmission may help reduce the morbidity and mortality associated with
      myasthenic crisis. 

PMID- 24744076
TI  - Reverse redistribution pattern in rest Tl-201 and stress Tc-99m SPECT in patients
      undergoing coronary interventions.

PMID- 24744077
TI  - Cutaneous Crohn's disease of the vulva.

PMID- 24744078
TI  - Crescent-in-doughnut sign and telescope sign of intussusception in Peutz-Jeghers
      syndrome.

PMID- 24744079
TI  - Herpes zoster ophthalmicus: is the globe involved?

PMID- 24744080
TI  - Rhinolith causing unilateral chronic maxillary rhinosinusitis.

PMID- 24744081
TI  - A broadcast-based key agreement scheme using set reconciliation for wireless body
      area networks.
AB  - Information and communication technologies have thrived over the last few years.
      Healthcare systems have also benefited from this progression. A wireless body
      area network (WBAN) consists of small, low-power sensors used to monitor human
      physiological values remotely, which enables physicians to remotely monitor the
      health of patients. Communication security in WBANs is essential because it
      involves human physiological data. Key agreement and authentication are the
      primary issues in the security of WBANs. To agree upon a common key, the nodes
      exchange information with each other using wireless communication. This
      information exchange process must be secure enough or the information exchange
      should be minimized to a certain level so that if information leak occurs, it
      does not affect the overall system. Most of the existing solutions for this
      problem exchange too much information for the sake of key agreement; getting this
      information is sufficient for an attacker to reproduce the key. Set
      reconciliation is a technique used to reconcile two similar sets held by two
      different hosts with minimal communication complexity. This paper presents a
      broadcast-based key agreement scheme using set reconciliation for secure
      communication in WBANs. The proposed scheme allows the neighboring nodes to agree
      upon a common key with the personal server (PS), generated from the
      electrocardiogram (EKG) feature set of the host body. Minimal information is
      exchanged in a broadcast manner, and even if every node is missing a different
      subset, by reconciling these feature sets, the whole network will still agree
      upon a single common key. Because of the limited information exchange, if an
      attacker gets the information in any way, he/she will not be able to reproduce
      the key. The proposed scheme mitigates replay, selective forwarding, and denial
      of service attacks using a challenge-response authentication mechanism. The
      simulation results show that the proposed scheme has a great deal of adoptability
      in terms of security, communication overhead, and running time complexity, as
      compared to the existing EKG-based key agreement scheme.

PMID- 24744083
TI  - Engineering electronic properties of layered transition-metal dichalcogenide
      compounds through alloying.
AB  - Binary alloys present a promising venue for band gap engineering and tuning of
      other mechanical and electronic properties of materials. Here we use the density
      functional theory and cluster expansion to investigate the thermodynamic
      stability and electronic properties of 2D transition metal dichalcogenide (TMD)
      binary alloys. We find that mixing electron-accepting or electron-donating
      transition metals with 2D TMD semiconductors leads to degenerate p- or n-doping,
      respectively, effectively rendering them metallic. We then proceed to investigate
      the electronic properties of semiconductor-semiconductor alloys. The exploration
      of the configurational space of the 2D molybdenum-tungsten disulfide (Mo1-xWxS2)
      alloy beyond the mean field approximation yields insights into anisotropy of the
      electron and hole effective masses in this material. The effective hole mass in
      the 2D Mo1-xWxS2 is nearly isotropic and is predicted to change almost linearly
      with the tungsten concentration x. In contrast, the effective electron mass shows
      significant spatial anisotropy. The values of the band gap in 2D Mo1-xWxS2 and
      MoSe2(1-x)S2x are found to be configuration-dependent, exposing the limitations
      of the mean field approach to band gap analysis in alloys. 

PMID- 24744082
TI  - Feasibility and evaluation of a pilot community health worker intervention to
      reduce hospital readmissions.
AB  - OBJECTIVE: To pilot-test the feasibility and preliminary effect of a community
      health worker (CHW) intervention to reduce hospital readmissions. DESIGN: Patient
      level randomized quality improvement intervention. SETTING: An academic medical
      center serving a predominantly low-income population in the Boston, Massachusetts
      area and 10 affiliated primary care practices. PARTICIPANTS: Medical service
      patients with an in-network primary care physician who were discharged to home (n
      = 423) and had one of five risk factors for readmission within 30 days.
      INTERVENTION: Inpatient introductory visit and weekly post-discharge telephonic
      support for 4 weeks to assist patient in coordinating medical visits, obtaining
      and using medications, and in self-management. MAIN OUTCOME MEASURES: Number of
      completed CHW contacts; CHW-reported barriers and facilitators to assisting
      patients; primary care, emergency department and inpatient care use. RESULTS:
      Roughly 70% of patients received at least one post-discharge CHW call; only 38%
      of patients received at least four calls as intended. Hospital readmission rates
      were lower among CHW patients (15.4%) compared with usual care (17.9%); the
      difference was not statistically significant. CONCLUSION: Under performance-based
      payment systems, identifying cost-effective solutions for reducing hospital
      readmissions will be crucial to the economic survival of all hospitals,
      especially safety-net systems. This pilot study suggests that with appropriate
      supportive infrastructure, hospital-based CHWs may represent a feasible strategy
      for improving transitional care among vulnerable populations. An ongoing,
      randomized, controlled trial of a CHW intervention, developed according to the
      lessons of this pilot, will provide further insight into the utility of this
      approach to reducing readmissions.

PMID- 24744084
TI  - Effect of side chain length on intrahelical interactions between carboxylate- and
      guanidinium-containing amino acids.
AB  - The charge-containing hydrophilic functionalities of encoded charged amino acids
      are linked to the backbone via different numbers of hydrophobic methylenes,
      despite the apparent electrostatic nature of protein ion pairing interactions. To
      investigate the effect of side chain length of guanidinium- and carboxylate
      containing residues on ion pairing interactions, alpha-helical peptides
      containing Zbb-Xaa (i, i + 3), (i, i + 4) and (i, i + 5) (Zbb = carboxylate
      containing residues Aad, Glu, Asp in decreasing length; Xaa = guanidinium
      residues Agh, Arg, Agb, Agp in decreasing length) sequence patterns were studied
      by circular dichroism spectroscopy (CD). The helicity of Aad- and Glu-containing
      peptides was similar and mostly pH independent, whereas the helicity of Asp
      containing peptides was mostly pH dependent. Furthermore, the Arg-containing
      peptides consistently exhibited higher helicity compared to the corresponding Agp
      , Agb-, and Agh-containing peptides. Side chain conformational analysis by
      molecular mechanics calculations showed that the Zbb-Xaa (i, i + 3) and (i, i +
      4) interactions mainly involved the chi 1 dihedral combinations (g+, g+) and (g-,
      g+), respectively. These low energy conformations were also observed in
      intrahelical Asp-Arg and Glu-Arg salt bridges of natural proteins. Accordingly,
      Asp and Glu provides variation in helix characteristics associated with Arg, but
      Aad does not provide features beyond those already delivered by Glu. Importantly,
      nature may have chosen the side chain length of Arg to support helical
      conformations through inherent high helix propensity coupled with stabilizing
      intrahelical ion pairing interactions with the carboxylate-containing residues. 

PMID- 24744085
TI  - Spondyloarthritis in sub-Saharan Africa.
AB  - Spondyloarthritis (SpA) is generally uncommon in sub-Saharan Africa, in part
      because of the rarity of HLA-B27 in this region. However, the relationship
      between HLA-B27 and SpA, particularly ankylosing spondylitis (AS), is complex.
      Despite the HLA-B 27:05 risk allele occurring in some West African populations,
      associated AS is not seen. In fact, most patients with AS are HLA-B27-negative,
      although there is emerging evidence that another class I HLA molecule, HLA-B
      14:03, is associated with AS in black Africans. The Assessment of
      SpondyloArthritis International Society criteria for detecting early axial
      disease are of limited value in sub-Saharan Africa, because of both the rarity of
      HLA-B27 and very limited access to magnetic resonance imaging. Reactive arthritis
      (ReA), psoriatic arthritis, and undifferentiated SpA are seen mainly in the
      context of HIV infection, although the exact effect of the virus in the
      pathogenesis of arthritis is unclear. In Zambia, ReA is associated with the HLA
      B*57:03 allele, which is paradoxically also associated with slow progression of
      HIV infection. HIV-associated ReA has a more protracted and aggressive course
      than standard ReA. Enthesitis-related arthritis is more common in children
      infected with HIV by vertical mother-to child transmission. Use of TNF inhibitors
      for axial disease is problematic, mainly because of cost, but also because of
      potential safety problems, especially reactivation of tuberculosis.

PMID- 24744086
TI  - Kawasaki disease: pathophysiology, clinical manifestations, and management.
AB  - Kawasaki Disease, a systemic vasculitis of unknown origin with specific
      predilection for the coronary arteries, is the most common cause of childhood
      acquired heart disease in western countries. Despite its world-wide incidence,
      the pathophysiology of this enigmatic disease is still under investigation.
      Diagnosis is made on a clinical basis, with supportive laboratory evidence and
      imaging. Once identified, timely initiation of treatment is imperative in order
      to quell the inflammatory response and decrease the incidence of long-term
      sequelae, specifically coronary artery aneurysms. Finally, longitudinal follow-up
      should be implemented based on risk stratification and individualized to each
      patient. 

PMID- 24744087
TI  - Patient courage leads us to wonder: should we perform face-lifts on patients
      taking coumadin?

PMID- 24744088
TI  - Identification of neurons responsible for feeding behavior in the Drosophila
      brain.
AB  - Drosophila melanogaster feeds mainly on rotten fruits, which contain many kinds
      of sugar. Thus, the sense of sweet taste has evolved to serve as a dominant
      regulator and driver of feeding behavior. Although several sugar receptors have
      been described, it remains poorly understood how the sensory input is transformed
      into an appetitive behavior. Here, we used a neural silencing approach to screen
      brain circuits, and identified neurons labeled by three Gal4 lines that modulate
      Drosophila feeding behavior. These three Gal4 lines labeled neurons mainly in the
      suboesophageal ganglia (SOG), which is considered to be the fly's primary taste
      center. When we blocked the activity of these neurons, flies decreased their
      sugar consumption significantly. In contrast, activation of these neurons
      resulted in enhanced feeding behavior and increased food consumption not only
      towards sugar, but to an array of food sources. Moreover, upon neuronal
      activation, the flies demonstrated feeding behavior even in the absence of food,
      which suggests that neuronal activation can replace food as a stimulus for
      feeding behavior. These findings indicate that these Gal4-labeled neurons, which
      function downstream of sensory neurons and regulate feeding behavior towards
      different food sources is necessary in Drosophila feeding control. 

PMID- 24744089
TI  - Relationship between salivary cortisol and depression in adolescent survivors of
      a major natural disaster.
AB  - The purpose of this study was to determine the utility of salivary cortisol
      levels for screening mental states such as depression in adolescents following a
      natural disaster. We examined the relationship of salivary cortisol levels in
      adolescent survivors of the 2011 Tohoku Earthquake with the depression subscale
      of the 28-item General Health Questionnaire (GHQ). Subjects were 63 adolescent
      survivors (age = 14.29 years +/- 0.51) who were administered the GHQ and provided
      saliva samples thrice daily (morning, afternoon and evening) over the course of 3
      days. Based on the GHQ-depression subscores, subjects were divided into low and
      high depression groups. About 22 % of the subjects were classified into the high
      symptom group. When data collected over 3 days were used, a significant
      difference was observed between the two groups in the salivary cortisol levels at
      the evening time point as well the ratio of the morning/evening levels (p <
      0.05). Analyzed by means of receiver-operating characteristic curves, the
      morning/evening ratios showed a good power in discriminating between subjects
      with and without depressive symptoms. Our study suggests that repeated
      measurement of salivary cortisol levels over 3 days has utility in screening for
      depressive states in adolescents following a natural disaster.

PMID- 24744090
TI  - Lasers and losers in the eyes of the law: liability for head and neck procedures.
AB  - IMPORTANCE: Although some have noted that malpractice litigation may be
      "plateauing," defensive medical practices are pervasive and make up a
      considerable proportion of the "indirect" costs medicolegal issues contribute
      toward our health care system. Accordingly, these trends have spurred
      considerable interest in characterizing factors that play a role in alleged
      medical negligence, along with outcomes and awards. OBJECTIVES: To conduct a
      focused examination of malpractice litigation regarding laser procedures in the
      head and neck and to determine the reasons for initiating litigation as well as
      outcomes and awards. DESIGN AND SETTING: Retrospective analysis of the
      WestlawNext legal database, encompassing publicly available federal and state
      court records, to identify malpractice cases involving laser procedures in the
      head and neck. MAIN OUTCOMES AND MEASURES: Outcomes, awards, defendant specialty,
      and other allegations. RESULTS: Most cases (28 [82%]) included in this analysis
      involved female plaintiffs. Of 34 cases, 19 (56%) were resolved with a defendant
      verdict. The median indemnity was $150 000, and dermatologists,
      otolaryngologists, and plastic surgeons were the most commonly named defendants.
      The most common procedures were performed for age-related changes, acne scarring,
      hair removal, and vascular lesions, although there were also several rhinologic
      and airway cases. Of all cases, 25 (74%) involved cutaneous procedures, and
      common allegations noted included permanent injury (24 cases [71%]),
      disfigurement/scarring (23 [68%]), inadequate informed consent (17 [50%]),
      unnecessary/inappropriate procedure (15 [44%]), and burns (11 [32%]).
      Noncutaneous procedures had higher trending median payments ($600 000 vs $103
      000), although this comparison did not reach statistical significance (P = .09).
      CONCLUSIONS AND RELEVANCE: Procedures using lasers represent a potential target
      for malpractice litigation should an adverse event occur. Although
      cutaneous/cosmetic procedures were noted among cases included in this analysis,
      as well as other head and neck interventions, otolaryngologists were more likely
      to be named as defendants in the latter category. Although cases had modest
      indemnities compared with prior analyses, the potential for significant amounts
      was present. Inclusion into the informed consent process of specific factors
      detailed in this analysis may potentially decrease liability. In addition,
      physicians and patients should undergo comprehensive discussion regarding
      expectations as well as contingencies should adverse events occur. LEVEL OF
      EVIDENCE: 4.

PMID- 24744091
TI  - Prognostic and biological significance of proliferation and HER2 expression in
      the luminal class of breast cancer.
AB  - The definition of Luminal-B subclass of breast cancer (BC) varies in literature.
      In this study, we have compared the proliferation status; assessed using KI67
      labeling index (KI67-LI), and HER2-expression in estrogen receptor positive (ER+)
      BC to assess their impact on the biological and clinical characteristics of
      luminal-BC. 1547 (73.8 %) well-characterized clinically annotated stage I-III ER
      + BC were assessed for expression of KI67, HER2 (ASCO guidelines), and a large
      panel of relevant biomarkers (no = 37). 46.3 % of the cases show high KI67-LI
      (>13 %) and 8.4 % show HER2+ and both markers are positively associated with
      younger age, higher tumor grade and poorer outcome. High KI67-LI and HER2+ are
      associated with upregulation of ER-coactivators and proliferation-related markers
      and with downregulation of good prognostic markers. High KI67-LI is associated
      with larger size, advanced stage, and lymphovascular invasion (LVI) and with
      downregulation of luminal-enriched and DNA-damage repair markers. In contrast,
      HER2+ is associated with upregulation of ER-regulated proteins and E-cadherin.
      When analysis is restricted to high KI67-LI subgroup, HER2+ shows an association
      with upregulation of differentiation-associated proteins and E-cadherin.
      Conversely, within HER2+ class, high KI67-LI maintains its association with
      downregulation of differentiation-associated/luminal-enriched proteins. Outcome
      analyses indicate that both markers are independently associated with shorter
      survival but HER2+ is associated with a worse outcome. Although both are
      associated with high proliferation and poor prognosis within ER + BC, HER2+ is
      less frequent than high KI67-LI. Unlike KI67, HER2 seems to independently drive
      the aggressive behavior of ER+ tumors without downregulation of luminal proteins.

PMID- 24744092
TI  - Birth size in the most recent pregnancy and maternal mortality in premenopausal
      breast cancer by tumor characteristics.
AB  - The main aim of this study was to investigate possible associations between
      measures of offspring size at birth in the most recent pregnancy before
      premenopausal breast cancer diagnosis and the risks of maternal breast cancer
      mortality, taking tumor characteristics into account. We also aimed to
      investigate if these associations are modified by age at childbirth, time since
      childbirth, parity, and age at diagnosis. We followed 6,019 women from their date
      of premenopausal breast cancer (diagnosed from 1992 to 2008) until emigration,
      death or December 31st, 2009, whichever occurred first. We used Cox proportional
      hazard regression models, adjusted for parity, age at diagnosis, and education
      level, to estimate associations between women pregnancy, cancer characteristics
      and offspring birth characteristics, and mothers' mortality risk. In stratified
      analyses, mortality risks were estimated by tumor stage, ER or PR status. There
      was no association between offspring birth weight (HR = 1.00, 95 % CI 0.99-1.01,
      when used as a continuous variable), birth weight for gestational age or ponderal
      index, and premenopausal breast cancer mortality. Similarly, in analyses
      stratified by tumor stage, receptor status, and time difference between last
      pregnancy and date of diagnosis, we found no associations between birth size and
      breast cancer mortality. Our findings suggest that the hypothesis that
      "premenopausal breast cancer mortality is associated with offspring birth
      characteristics in the most recent pregnancy before the diagnosis" may not be
      valid. In addition, these associations are not modified by tumor characteristics.

PMID- 24744093
TI  - Tamoxifen-associated hot flash severity is inversely correlated with endoxifen
      concentration and CYP3A4*22.
AB  - Tamoxifen use is often limited in some patients due to adverse effects including
      severe hot flash symptoms. Tamoxifen undergoes hepatic bioactivation by CYP2D6
      and CYP3A4 to form the active metabolite endoxifen. It remains unclear whether
      the extent of attained endoxifen level or genetic polymorphisms in drug
      metabolizing enzymes is associated with the frequency and severity of hot
      flashes. We conducted a prospective study using self-reported surveys to assess
      tamoxifen side effects experienced during the week prior to clinic visits of 132
      female breast cancer patients on tamoxifen therapy, and hot flash severity scores
      were tabulated. At the time of clinic visit, blood samples were obtained to
      determine tamoxifen and its metabolite levels and to determine CYP2D6 and CYP3A4
      genotypes. The majority of participants (77 %) experienced hot flashes, with 11 %
      experiencing severe or very severe symptoms. We observed an inverse correlation
      between endoxifen concentration and hot flash severity score following adjustment
      for age, BMI, and menopausal status in patients with non-zero scores (p < 0.001).
      Interestingly, CYP2D6 genotype was not significantly associated with hot flash
      scores in patients on no known inhibitory medications. However, CYP3A4*22
      carriers were less likely to have hot flashes with an odds ratio of 8.87 (p <
      0.01) even when compared to a cohort with similar endoxifen levels. Our data
      demonstrate that patients with higher endoxifen levels tended to predict lower
      hot flash severity scores. Importantly, this is the first study to show CYP3A4*22
      genotype as an independent predictor of hot flash severity during tamoxifen
      therapy. 

PMID- 24744094
TI  - Erratum to: Clinical implication of ocular torsion in peripheral vestibulopathy.

PMID- 24744097
TI  - [Neurocognitive disorders in DSM-5: pervasive changes in the diagnostics of
      dementia].
AB  - The Diagnostic and Statistical Manual of Mental Disorders (DSM-5) proposes an
      innovative chapter on neurocognitive disorders (NCD) as a substitute for the
      dementia, delirium and amnestic disorders chapter in DSM-IV. This NCD chapter
      promotes a most innovative change compared to DSM-IV. While the term delirium is
      preserved, the commonly used term dementia does not occur as a diagnostic entity.
      Neurocognitive disorders are more inclusive than dementias; they also cover early
      prodromal stages of dementias below the DSM-IV threshold. The diagnosis of NCDs
      requires essentially neuropsychological testing preferentially with standardized
      instruments. Special focus is given to etiological subtyping taking former
      diagnostic consensus processes by expert groups into consideration. The
      subsequent more extensive concept of NCD also allows the diagnosis of etiological
      specific prodromal states of cognitive impairments. The changes from DSM-IV to
      DSM-5 are critically discussed.

PMID- 24744096
TI  - Biochemical characterisation of Troponin C mutations causing hypertrophic and
      dilated cardiomyopathies.
AB  - Cardiac muscle contraction occurs through an interaction of the myosin head with
      the actin filaments, a process which is regulated by the troponin complex
      together with tropomyosin and is Ca(2+) dependent. Mutations in genes encoding
      sarcomeric proteins are a common cause of familial hypertrophic and dilated
      cardiomyopathies. The scope of this review is to gather information from studies
      regarding the in vitro characterisation of six HCM and six DCM mutations on the
      cardiac TnC gene and to suggest, if possible, how they may lead to dysfunction.
      Since TnC is the subunit responsible for Ca(2+) binding, mutations in the TnC
      could possibly have a strong impact on Ca(2+) binding affinities. Furthermore,
      the interactions of mutant TnCs with their binding partners could be altered.
      From the characterisation studies available to date, we can conclude that the HCM
      mutations on TnC increase significantly the Ca(2+) sensitivity of force
      development or of ATPase activity, producing large pCa shifts in comparison to WT
      TnC. In contrast, the DCM mutations on TnC have a tendency to decrease the Ca(2+)
      sensitivity of force development or of ATPase activity in comparison to WT TnC.
      Furthermore, the DCM mutants of TnC are not responsive to the TnI phosphorylation
      signal resulting in filaments that preserve their Ca(2+) sensitivity in contrast
      to WT filaments that experience a decrease in Ca(2+) sensitivity upon TnI
      phosphorylation.

PMID- 24744098
TI  - Coiled fiber scaffolds embedded with gold nanoparticles improve the performance
      of engineered cardiac tissues.
AB  - Coiled perimysial fibers within the heart muscle provide it with the ability to
      contract and relax efficiently. Here, we report on a new nanocomposite scaffold
      for cardiac tissue engineering, integrating coiled electrospun fibers with gold
      nanoparticles. Cultivation of cardiac cells within the hybrid scaffolds promoted
      cell organization into elongated and aligned tissues generating a strong
      contraction force, high contraction rate and low excitation threshold. 

PMID- 24744099
TI  - Helminth/Parasite treatment of multiple sclerosis.
AB  - OPINION STATEMENT: Epidemiological studies suggest that autoimmune diseases, such
      as multiple sclerosis (MS), are less frequent in individuals who are helminth
      carriers. This observation has been tested in murine models of colitis, MS, type
      1 diabetes and asthma. In each case, mice colonized with helminths show
      protection from disease. This apparent down-modulation of inflammatory response
      resulting from helminth infection has triggered interest in exploring the
      potential clinical efficacy of controlled helminth infection in patients
      suffering from autoimmune diseases. To date, clinical trials using helminth
      therapy (Trichura suis ova [TSO] or Necator americanus larvae) in MS have been
      small, safety-oriented trials of short duration, attempting to reproduce and
      confirm epidemiological and experimental data. Thus far, no adverse events
      related to therapeutic helminth infection have been observed. Nonetheless, there
      is a clear need for caution when considering such approaches. Some preliminary
      clinical, magnetic resonance imaging and immunological outcomes using TSO have
      been encouraging. Nevertheless, results should be interpreted with caution as the
      number of individuals studied was small and duration of follow up limited. Longer
      studies, monitoring safety and objective outcome measures are necessary to assess
      this novel therapeutic strategy in a more definitive fashion. An alternative
      approach to use of live helminth infections might arise from identification of
      helminth-derived immunomodulatory molecules mimicking the protective effects of
      parasite infection, i.e. capable of altering immune responses and, therefore, the
      course of autoimmune diseases. Although positive results from administering
      parasite products in mouse models of autoimmunity have been reported, much
      remains to be explored before the field can move from experimental animal models
      to application in clinical practice. To the best of my knowledge, parasite
      derived molecules have not yet been administered as treatment for any autoimmune
      disease in humans. At this time, it is strongly recommended that live helminth or
      ova parasites be administered only to individuals participating in strictly
      monitored, controlled clinical trials.

PMID- 24744100
TI  - Right Aortic Arch With Kommerell Diverticulum: A Rare Cause of Dysphagia.
AB  - IMPORTANCE: Dysphagia is a common condition with multiple causes. Fortunately, a
      thorough evaluation will often lead to a correct diagnosis, even when the cause
      is a rare entity. A right aortic arch with associated aberrant left subclavian
      artery is an uncommon anatomical variant. Physicians involved in the management
      of dysphagia should be aware of vascular anomalies that can cause dysphagia.
      OBSERVATIONS: We report a case of a young patient who presented with dysphagia
      caused by a right aortic arch, aberrant left subclavian artery, and associated
      Kommerell diverticulum, a remnant of the left dorsal arch. CONCLUSIONS AND
      RELEVANCE: Kommerell diverticulum, a remnant of the left dorsal arch, is a rare
      cause of dysphagia. However, vascular causes should be considered in the
      algorithm when evaluating patients who present with dysphagia, especially when
      there is compression of the esophagus noted on imaging or examination.

PMID- 24744101
TI  - Novel use of a guidewire to facilitate intubation in an obstructing anterior
      mediastinal mass.
AB  - PURPOSE: This report describes the management of a life-threatening tracheal
      obstruction due to a thymoma in the anterior mediastinum and the use of a
      guidewire to facilitate intubation. CLINICAL FEATURES: Anesthetic management of
      patients presenting with large anterior mediastinal masses is always challenging.
      Catastrophic complications can occur after loss of consciousness due to
      compression of the airway, heart, or great vessels. Intrathoracic airway
      compression may become complete with a life-threatening inability to ventilate
      the lungs. We discuss the management of this case presenting to a regional centre
      prior to transfer to a tertiary care facility and point out current
      recommendations for pre-induction assessment and airway management in similar
      cases. CONCLUSION: Confirmed guidewire placement prior to induction enabled
      intubation in a setting without cardiothoracic backup capabilities.

PMID- 24744102
TI  - Direct pressure on a pseudomeningocele resulting in intraoperative cerebral
      ischemia.
AB  - PURPOSE: When positioning patients with meningocele and meningomyelocele, it is
      standard practice to avoid direct pressure on the lesions. That caution is
      intended to prevent injury to neural elements within the lesion and violation of
      the cerebrospinal fluid space. We herein report an additional hazard of direct
      intraoperative pressure on such lesions. An adult patient with a lumbosacral
      pseudomeningocele sustained a cerebral ischemic injury as a consequence of direct
      pressure on the lesion during general anesthesia. CLINICAL FEATURES: A 32-yr-old
      male with spina bifida and a pseudomeningocele related to recent lumbar surgery
      underwent a urologic procedure in the lithotomy position. Because the lesion was
      recognized to lie to the left of the midline, cushioning was placed under the
      patient's left hip and buttock. The patient was slow to awaken and has sustained
      significant long-term cognitive deficits. Imaging is consistent with a diffuse
      cerebral ischemic insult. CONCLUSION: In retrospect, the size and leftward extent
      of the pseudomeningocele were not appreciated preoperatively, and in spite of the
      care taken, intraoperative pressure was placed on the lesion. This report
      cautions that intraoperative pressure related to positioning patients with extra
      axial lesions containing cerebrospinal fluid (CSF), e.g., meningoceles and
      pseudomeningoceles, can result in increases in CSF pressure and thereby a
      reduction in cerebral perfusion pressure sufficient to result in cerebral
      ischemia.

PMID- 24744104
TI  - Havens of risks or resources? A study of two Latino neighborhoods in New York
      City.
AB  - Research has been mixed on the potential risks and resources that ethnic enclaves
      may confer upon residents: whereas some authors characterize racial and ethnic
      minority neighborhoods through the lens of segregation and risk, others argue
      that these minority neighborhoods are ethnic enclaves that can improve the
      availability of resources to residents. In this study, we sought to assess two
      predominantly Latino New York City neighborhoods (one enclave neighborhood and
      one comparison) in the areas of structural resources (e.g., grocers, parks),
      cultural resources (e.g., botanicas, hair salons), and risks (e.g., empty lots,
      bars) by street-level coding in 20 census tracts (streets N = 202). We used
      Poisson generalized linear models to assess whether enclave status of a
      neighborhood predicted the numbers of risks and resources on streets within those
      neighborhoods. Enclave status did not predict the number of risks (Rate ratio =
      1.08(0.83, 1.42), chi (2)(1, N = 202) = 0.35, p = n. s.) or cultural resources
      (Rate ratio = 0.87(0.54, 1.40), chi (2)(1, N = 202) = 0.34, p = n. s.), yet it
      was associated with a higher number of structural resources (Rate ratio =
      1.90(1.48, 2.43), chi (2)(1, N = 202) = 25.74, p < 0.001). The results suggest
      that while living in an ethnic enclave may not reduce risks, it may help
      residents cope with those risks through an increased number of structural
      resources. These findings support theories that conceptualize ethnic enclaves as
      neighborhoods where greater resources are available to residents. The focus on
      resources within this work was instrumental, as no difference would have been
      found if a solely risk-focused approach had been employed.

PMID- 24744105
TI  - Community-based harm reduction substance abuse treatment with methamphetamine
      using men who have sex with men.
AB  - Harm reduction approaches endeavor to assist individuals with avoiding the most
      detrimental consequences of risk taking behaviors, but limited research has
      documented the outcomes of harm reduction substance abuse treatment. In total,
      211 methamphetamine-using men who have sex with men (MSM) enrolled in two outcome
      studies of substance abuse treatment programs that were implementing an evidence
      based, cognitive-behavioral intervention (i.e., the Matrix Model) from a harm
      reduction perspective. Study 1 (N = 123) examined changes in self-reported
      substance use, Addiction Severity Index (ASI) composite scores, and HIV care
      indicators over a 12-month follow-up. Study 2 (N = 88) assessed changes in
      substance use, sexual risk taking, and HIV care indicators over a 6-month follow
      up. Participants in study 1 reported reductions in cocaine/crack use as well as
      decreases in the ASI drug and employment composite scores. Among HIV-positive
      participants in study 1 (n = 75), 47 % initiated or consistently utilized anti
      retroviral therapy and this was paralleled by significant increases in self
      reported undetectable HIV viral load. Study 2 participants reported reductions in
      methamphetamine use, erectile dysfunction medication use in combination with
      other substances, and sexual risk-taking behavior while using methamphetamine.
      Participants in both studies reported concurrent increases in marijuana use.
      Taken together, these studies are among the first to observe that clients may
      reduce stimulant use and concomitant sexual risk-taking behavior during harm
      reduction substance abuse treatment. Randomized controlled trials are needed to
      examine the differential effectiveness of harm reduction and abstinence-based
      approaches to substance abuse treatment.

PMID- 24744103
TI  - The developing story of Sprouty and cancer.
AB  - Sprouty proteins are evolutionarily conserved modulators of MAPK/ERK pathway.
      Through interacting with an increasing number of effectors, mediators, and
      regulators with ultimate influence on multiple targets within or beyond ERK,
      Sprouty orchestrates a complex, multilayered regulatory system and mediates a
      crosstalk among different signaling pathways for a coordinated cellular response.
      As such, Sprouty has been implicated in various developmental and physiological
      processes. Evidence shows that ERK is aberrantly activated in malignant
      conditions. Accordingly, Sprouty deregulation has been reported in different
      cancer types and shown to impact cancer development, progression, and metastasis.
      In this article, we have tried to provide an overview of the current knowledge
      about the Sprouty physiology and its regulatory functions in health, as well as
      an updated review of the Sprouty status in cancer. Putative implications of
      Sprouty in cancer biology, their clinical relevance, and their proposed
      applications are also revisited. As a developing story, however, role of Sprouty
      in cancer remains to be further elucidated. 

PMID- 24744107
TI  - [Process design in high-reliability organizations].
AB  - Modern medicine is a highly complex service industry in which individual care
      providers are linked in a complicated network. The complexity and interlinkedness
      is associated with risks concerning patient safety. Other highly complex
      industries like commercial aviation have succeeded in maintaining or even
      increasing its safety levels despite rapidly increasing passenger figures.
      Standard operating procedures (SOPs), crew resource management (CRM), as well as
      operational risk evaluation (ORE) are historically developed and trusted parts of
      a comprehensive and systemic safety program. If medicine wants to follow this
      quantum leap towards increased patient safety, it must intensively evaluate the
      results of other high-reliability industries and seek step-by-step implementation
      after a critical assessment. 

PMID- 24744108
TI  - [Complications associated with inguinal orchiectomy and scrotal orchiectomy].
AB  - Inguinal excision of testis is technically an elementary surgical procedure.
      According to the indication (e.g., malignant tumors, infarction, inflammation),
      an inguinal or alternatively a transcrotal approach is possible. Despite its
      straightforwardness, surgery of the scrotum includes remarkable risks and
      complications such as postoperative hemorrhage, hematoma formation, infections,
      and disturbances of wound healing followed by insufficient unfavorable cosmetic
      results. Nerve injury may be accompanied by temporary or persistent paresthesias
      which have been documented in our patients undergoing orchiectomy. 

PMID- 24744106
TI  - Heme oxygenase-1 regulates cell proliferation via carbon monoxide-mediated
      inhibition of T-type Ca2+ channels.
AB  - Induction of the antioxidant enzyme heme oxygenase-1 (HO-1) affords cellular
      protection and suppresses proliferation of vascular smooth muscle cells (VSMCs)
      associated with a variety of pathological cardiovascular conditions including
      myocardial infarction and vascular injury. However, the underlying mechanisms are
      not fully understood. Over-expression of Cav3.2 T-type Ca(2+) channels in HEK293
      cells raised basal [Ca(2+)]i and increased proliferation as compared with non
      transfected cells. Proliferation and [Ca(2+)]i levels were reduced to levels seen
      in non-transfected cells either by induction of HO-1 or exposure of cells to the
      HO-1 product, carbon monoxide (CO) (applied as the CO releasing molecule, CORM
      3). In the aortic VSMC line A7r5, proliferation was also inhibited by induction
      of HO-1 or by exposure of cells to CO, and patch-clamp recordings indicated that
      CO inhibited T-type (as well as L-type) Ca(2+) currents in these cells. Finally,
      in human saphenous vein smooth muscle cells, proliferation was reduced by T-type
      channel inhibition or by HO-1 induction or CO exposure. The effects of T-type
      channel blockade and HO-1 induction were non-additive. Collectively, these data
      indicate that HO-1 regulates proliferation via CO-mediated inhibition of T-type
      Ca(2+) channels. This signalling pathway provides a novel means by which
      proliferation of VSMCs (and other cells) may be regulated therapeutically. 

PMID- 24744109
TI  - [Error prevention through management of complications in urology: standard
      operating procedures from commercial aviation as a model].
AB  - Patient safety and risk/complication management rank among the current megatrends
      in modern medicine, which has undoubtedly become more complex. In time-critical,
      error-prone and difficult situations, which often occur repeatedly in everyday
      clinical practice, guidelines are inappropriate for acting rapidly and
      intelligently. With the establishment and consistent use of standard operating
      procedures like in commercial aviation, a possible strategic approach is
      available. These medical aids to decision-making - quick reference cards - are
      short, optimized instructions that enable a standardized procedure in case of
      medical claims. 

PMID- 24744110
TI  - Neutralization of pathogenic beta1-receptor autoantibodies by aptamers in vivo:
      the first successful proof of principle in spontaneously hypertensive rats.
AB  - Autoantibodies (AABs) against the second extracellular loop of the beta1-receptor
      (beta1(II)-AABs) are found as a pathogenic driver in patients with idiopathic
      dilated cardiomyopathy, Chagas cardiomyopathy, peripartum cardiomyopathy, and
      myocarditis, and have been increasingly seen as a treatment target. We recently
      identified an aptamer (single short DNA strand) that specifically binds and
      neutralizes beta1(II)-AABs. Via application of this aptamer, a new treatment
      strategy for diseases associated with the cardio-pathogenic beta1(II)-AABs could
      be developed. Spontaneously hypertensive rats (SHR) positive for beta1(II)-AABs
      were treated five times at weekly intervals (bolus application of 2 mg/kg body
      weight followed by an infusion of the same amount over 20 min). SHR responded to
      aptamer treatment with a strong reduction in the cardio-pathogenic beta1(II)
      AABs. The AABs did not substantially return within the study period. No signs for
      aptamer toxicity were observed by visual examination of the heart, liver, and
      kidney, or by measurement of plasma CK, ALT, and creatinine. The aptamer's
      potential for beta1(II)-AAB neutralization and consequently for cardiomyopathy
      treatment has been shown for the first time in vivo.

PMID- 24744111
TI  - Open-globe injuries at an emergency department in Porto, Portugal: clinical
      features and prognostic factors.
AB  - PURPOSE: To describe the epidemiology, characteristics, surgical management,
      functional outcome, and prognostic factors of open-globe injuries requiring
      surgical treatment. METHODS: A retrospective review of 180 patients who underwent
      surgical repair of an open-globe injury at the ophthalmology emergency department
      of the Hospital S. Joao (Porto-Portugal) was performed. Prognostic factors for no
      light perception and for poor vision (visual acuity <3/10) in patients who
      retained vision after surgical treatment were determined. RESULTS: We observed a
      different age distribution between male and female ocular trauma (143 patients
      were men, with a mean age of 46.4 years, while the mean age for women was 70.9
      years). Domestic accidents were the most frequent context of trauma (44.4%).
      However, work accidents constituted the principal context of trauma among men.
      Initial visual acuity, concomitant adnexa lesion, associated nonocular trauma,
      and intentionally caused trauma were predictors of no vision at the end of the
      follow-up. Older age, lens damage, and retinal detachment were predictors of poor
      vision in patients with retained visual acuity. Vitreous hemorrhage, posterior
      segment lesion, and simultaneous lesion of anterior and posterior segment
      anticipated both no vision and poor vision. Isolated anterior segment lesion was
      associated with vision survival and good vision (>=3/10). CONCLUSIONS: The
      prognostic factors identified in this study may aid the process of decision
      making in 2 crucial moments: at the initial approach and during the follow-up of
      patients with vision survival after open-globe injuries.

PMID- 24744112
TI  - Racial and Ethnic Disparities in Salivary Gland Cancer Survival.
AB  - IMPORTANCE: Several recent US studies have documented racial disparities in head
      and neck cancer outcomes, but few have investigated racial and ethnic differences
      in salivary gland cancer (SGCA) survival. OBJECTIVE: To determine whether patient
      race or ethnicity affects SGCA survival. DESIGN, SETTING, AND PARTICIPANTS:
      Retrospective survival analysis of all patients with SGCA from 1988 through 2010
      in the Surveillance, Epidemiology, and End Results database. MAIN OUTCOMES AND
      MEASURES: Disease-specific survival according to race and ethnicity. End points
      assessed included age at diagnosis, sex, tumor grade, tumor size at diagnosis,
      extension at diagnosis, lymph node involvement at diagnosis, and treatment.
      Results were further analyzed by histologic subtype of SGCA. RESULTS: Of 11,007
      patients with SGCA, 1073 (9.7%) were black, and 1068 (9.7%), Hispanic. Whites'
      mean age at diagnosis was 63 years vs 53 and 52 years for blacks and Hispanics,
      respectively (P < .001). Twenty-year disease-specific survival rates for all SGCA
      histologic subtypes combined for whites, blacks, and Hispanics were 78%, 79%, and
      81%, respectively. Unadjusted survival curves showed no significant difference
      between blacks and whites and an apparent advantage for Hispanics. However,
      multivariable Cox regression models controlling for patient, tumor, and treatment
      characteristics showed poorer disease-specific survival vs whites for blacks
      (hazard ratio [HR], 1.22 [95% CI, 1.03-1.46]; P = .03) but not for Hispanics (HR,
      0.97 [0.79-1.19]; P = .77). The overall disease-specific survival disparity was
      due to poorer disease-specific survival for blacks vs whites with mucoepidermoid
      (P = .03) and squamous cell carcinomas (P = .05). Less surgical treatment for
      blacks than whites (57.26% vs 76.94%; P < .001) was a source of the survival
      disparity for squamous cell but not mucoepidermoid SGCA. CONCLUSIONS AND
      RELEVANCE: Black race is a risk factor for poorer disease-specific survival for
      patients with mucoepidermoid or squamous cell carcinoma, whereas Hispanic
      ethnicity has no effect. Differing treatment between black and white patients
      affects survival in squamous cell but not mucoepidermoid SGCA. Differences in
      chemotherapy treatment, comorbidities, socioeconomic status, tumor genetic
      factors, and environmental exposures are potential but unproven additional
      sources of the racial survival disparities for mucoepidermoid and squamous cell
      SGCA.

PMID- 24744113
TI  - Rapid formation of Ag(n)X(X = S, Cl, PO4, C2O4) nanotubes via an acid-etching
      anion exchange reaction.
AB  - This work presents a rapid nanotube fabrication method for a series of silver
      compounds AgnX, such as Ag2S, AgCl, Ag3PO4, and Ag2C2O4, from pregrown Ag2CO3
      nanorod templates. The anion exchange process involved takes place in non-aqueous
      solutions just at room temperature and completes within 10 minutes. An acid
      etching anion exchange reaction mechanism has been proved underneath the
      transformation process from Ag2CO3 nanorods to AgnX nanotubes by the observation
      of an intermediate yolk-shell nanostructure. It has been found that the final
      structure of the products can be conveniently controlled by simply varying the
      concentration of HnX acids, and the organic solvents employed play a vital role
      in the formation of the nanotubes by effectively controlling the diffusion rates
      of different species of reacting ions. As a demonstration, the as-prepared AgCl
      and Ag3PO4 nanotubes exhibit enhanced photocatalytic activity and favorable
      recyclability for the photodegradation of rhodamine B (RhB) under visible-light
      irradiation. 

PMID- 24744114
TI  - Predictors of bone mineral density improvement in patients undergoing
      parathyroidectomy for primary hyperparathyroidism.
AB  - INTRODUCTION: Primary hyperparathyroidism (PHPT) results in increased bone
      turnover, resulting in bone mineral density (BMD) reduction and a predisposition
      towards fractures. Parathyroidectomy (PTX) is the only definitive cure.
      OBJECTIVE: The primary goals of this study were to investigate the impact of PTX
      on BMD in patients with PHPT and to identify factors associated with post
      operative BMD improvement using a multivariate model. METHODS: Between 1999 and
      2010, a total of 757 patients underwent PTX for treatment of PHPT; 123 patients
      had both a pre- and a post-operative dual-energy X-ray absorptiometry (DEXA)
      scan. A prospective database was queried to obtain information about patient
      demographics, medications, comorbidities, and pre- and post-operative laboratory
      values. A Cox regression model was used to stratify patients and to identify
      factors that independently predict BMD response following PTX in this patient
      population. RESULTS: Overall, mean percent change in BMD was +12.31 % at the
      spine, +8.9 % at the femoral neck (FN), and +8.5 % at the hip, with a mean follow
      up of 2.3 +/- 1.5 years. A total of 101 (82.1 %) patients had BMD improvement at
      their worst pre-operative site. In patients who improved, 69.9 % (n = 86) had >5
      % increase. Factors associated with BMD improvement at the worst pre-operative
      site were as follows: male gender (hazard ratio [HR] 2.29; 95 % confidence
      interval [CI] 1.54-4.21); pre-operative BMD with T-score less than -2.0 (HR 1.89;
      95 % CI 1.11-2.39); age <55 years (HR 1.74; 95 % CI 1.14-2.25); BMD DEXA scan at
      >2.5 years post-operatively (HR 1.71; 95 % CI 1.09-2.17); history of previous
      fracture (HR 1.24; 95 % CI 1.05-1.92); and private insurance (HR 1.18; 95 % CI
      1.06-2.1). The use of bisphosphonates, estrogens, vitamin D supplementation, or
      tobacco; obesity; history of previous PTX, serum calcium or parathyroid hormone
      levels were not independently associated with post-operative BMD improvement.
      CONCLUSION: Osteoporosis is one of the established National Institutes of Health
      criteria for PTX in asymptomatic patients with PHPT, but BMD improvement is not
      consistently seen during the post-operative period. Gender, age, more severe pre
      operative bone disease, and insurance status were all predictors for greater BMD
      improvement following PTX. Further studies with a rigorous post-operative BMD
      regimen are needed in order to validate these results.

PMID- 24744115
TI  - Applying value sensitive design (VSD) to wind turbines and wind parks: an
      exploration.
AB  - Community acceptance still remains a challenge for wind energy projects. The most
      popular explanation for local opposition, the Not in My Backyard effect, has
      received fierce criticism in the past decade. Critics argue that opposition is
      not merely a matter of selfishness or ignorance, but that moral, ecological and
      aesthetic values play an important role. In order to better take such values into
      account, a more bottom-up, participatory decision process is usually proposed.
      Research on this topic focusses on either stakeholder motivations/attitudes, or
      their behavior during project implementation. This paper proposes a third
      research focus, namely the 'objects' which elicit certain behavioral responses
      and attitudes-the wind turbine and parks. More concretely, this paper explores
      Value Sensitive Design (VSD) as way to arrive at wind turbines and parks that
      better embed or reflect key values. After a critical discussion of the notion of
      acceptance versus acceptability and support, the paper discusses existing
      literature on ecology and aesthetics in relation to wind turbine/park design,
      which could serve as 'building blocks' of a more integral VSD approach of the
      topic. It also discusses the challenge of demarcating wind park projects as VSD
      projects. A further challenge is that VSD has been applied mainly at the level of
      technical artifacts, whereas wind parks can best be conceptualized as socio
      technical system. This new application would therefore expand the current
      practice of VSD, and may as a consequence also lead to interesting new insights
      for the VSD community. The paper concludes that such an outcome-oriented approach
      of wind turbines and park is worth exploring further, as a supplement to rather
      than a replacement of the process-oriented approach that is promoted by the
      current literature on community acceptance of wind parks. 

PMID- 24744116
TI  - The capacity for ethical decisions: the relationship between working memory and
      ethical decision making.
AB  - Although various models of ethical decision making (EDM) have implicitly called
      upon constructs governed by working memory capacity (WMC), a study examining this
      relationship specifically has not been conducted. Using a sense making framework
      of EDM, we examined the relationship between WMC and various sensemaking
      processes contributing to EDM. Participants completed an online assessment
      comprised of a demographic survey, intelligence test, various EDM measures, and
      the Automated Operation Span task to determine WMC. Results indicated that WMC
      accounted for unique variance above and beyond ethics education, exposure to
      ethical issues, and intelligence in several sensemaking processes. Additionally,
      a marginally significant effect of WMC was also found with reference to EDM.
      Individual differences in WMC appear likely to play an important role in the
      ethical decision-making process, and future researchers may wish to consider
      their potential influences. 

PMID- 24744117
TI  - A survey of student opinions on ethical design standards in Taiwan.
AB  - Design ethics has been offered as a course in undergraduate design programs in
      Taiwan for over a decade, but research on teaching design ethics and the results
      of teaching these courses is scant. We conducted two tests to examine (1) the
      effect of an ethics course, and (2) the differences among the effects of design
      department, gender, and study year on student opinions regarding ethical design
      standards (EDSs) at the National Yunlin University of Science and Technology
      (YunTech) in Taiwan. The participants comprised 934 undergraduates (660 women and
      274 men) from the five design departments at YunTech's College of Design from
      Years 1-4. The results confirmed the effect of an ethics course on student EDS
      opinions. In addition, we observed significant variations among students
      according to design departments, suggesting that the characteristics of the
      design departments also affected students' EDS opinions. The results indicated
      that gender did not significantly affect design students' EDS opinions; however,
      students in their early years of study produced higher scores than those in their
      advanced years of study did, based on the six EDS opinions. The implications of
      these results for teaching design ethics and future research are discussed in
      this paper. 

PMID- 24744119
TI  - Educating low-SES and LEP survivors about breast cancer research: pilot test of
      the Health Research Engagement Intervention.
AB  - The Health Research Engagement Intervention (HREI) aims to reduce information and
      access disparities for breast cancer research opportunities among low
      socioeconomic status (SES) and limited English proficient (LEP) breast cancer
      survivors by providing neutral, non-trial-specific information about health
      research via a trusted patient navigator. Qualitative methods in the context of a
      community-based participatory research design were used to iteratively design the
      HREI in collaboration with community-based care navigators from a trusted
      community organization, Shanti Project, and to locate appropriate research
      studies in collaboration with a web-based trial-matching service,
      BreastCancerTrials.org (BCT). Navigators were first trained in clinical trials
      and health research and then to deliver the HREI, providing feedback that was
      incorporated into both the HREI design and BCT's interface. Our intervention
      pilot with low SES and LEP survivors (n = 12) demonstrated interest in learning
      about "health research." All 12 participants opted to obtain more information
      when offered the opportunity. Post-intervention questionnaires showed that three
      of 11 (27 %) participants independently pursued additional information about
      research opportunities either online or by phone in the week following the
      intervention. Post-intervention navigator questionnaires indicated that
      navigators could confidently and efficiently deliver the intervention. LEP
      patients who pursued information independently faced language barriers. The HREI
      is a promising and potentially scalable intervention to increase access to
      neutral information about breast cancer research opportunities for low-SES and
      LEP individuals. However, in order for it to be effective, systems barriers to
      participation such as language accessibility at sources of health research
      information must be addressed. 

PMID- 24744120
TI  - Engaging patients and caregivers in patient-centered outcomes research on
      advanced stage lung cancer: insights from patients, caregivers, and providers.
AB  - Participatory and patient-centered approaches to cancer research have been
      highlighted as the most appropriate means of engaging patients in the conduct of
      clinical research. However, there is a paucity of patient-centered outcomes
      research (PCOR) on lung cancer. Previous studies seeking to define lung cancer
      treatment success have generally not included patients' and caregivers'
      perceptions and views in treatment decision-making. Additionally, little is known
      about effective strategies for the engagement of lung cancer patients in PCOR. We
      sought to gain insights into the perceptions of patients, caregivers, and
      providers on lung cancer treatment success, as well as on strategies for patient
      engagement in lung cancer PCOR. Four focus groups were conducted with provider,
      patient, and caregiver participants from four cancer centers in Nebraska and
      South Dakota. A total of 36 providers, patients, and caregivers participated in
      this study. Patients and caregivers confirmed that survival alone should not be
      the measure of lung cancer treatment success and that definitions of treatment
      success should emphasize factors such as effective clinical guidance throughout
      treatment, symptom management, functionality, and quality of life. Clinician
      participants noted that the definition of treatment success evolved over time and
      appeared to be linked to patients' experiences with chemotherapy. Participants
      identified barriers to and facilitators of research participation and suggested
      strategies for the recruitment and retention of research participants. Our study
      indicates that patients can successfully play active and engaged roles in
      clinical research, ranging from participant to partner. Judging from the
      enthusiasm of our focus group attendees, patients and caregivers want to
      participate and be engaged in clinical research. 

PMID- 24744118
TI  - Astrocytic glycogenolysis: mechanisms and functions.
AB  - Until the demonstration little more than 20 years ago that glycogenolysis occurs
      during normal whisker stimulation glycogenolysis was regarded as a relatively
      uninteresting emergency procedure. Since then, a series of important astrocytic
      functions has been shown to be critically dependent on glycogenolytic activity to
      support the signaling mechanisms necessary for these functions to operate. This
      applies to glutamate formation and uptake and to release of ATP as a transmitter,
      stimulated by other transmitters or elevated K(+) concentrations and affecting
      not only other astrocytes but also most other brain cells. It is also relevant
      for astrocytic K(+) uptake both during the period when the extracellular K(+)
      concentration is still elevated after neuronal excitation, and capable of
      stimulating glycogenolytic activity, and during the subsequent undershoot after
      intense neuronal activity, when glycogenolysis may be stimulated by
      noradrenaline. Both elevated K(+) concentrations and several transmitters,
      including the beta-adrenergic agonist isoproterenol and vasopressin increase free
      cytosolic Ca(2+) concentration in astrocytes, which stimulates phosphorylase
      kinase so that it activates the transformation of the inactive glycogen
      phosphorylase a to the active phosphorylase b. Contrary to common belief cyclic
      AMP plays at most a facilitatory role, and only when free cytosolic Ca(2+)
      concentration is also increased. Cyclic AMP is not increased during activation of
      glycogenolysis by either elevated K(+) concentrations or the stimulation of the
      serotonergic 5-HT(2B) receptor. Not all agents that stimulate glycogenolysis do
      so by directly activating phophorylase kinase--some do so by activating processes
      requiring glycogenolysis, e.g. for synthesis of glutamate.

PMID- 24744121
TI  - CXCL12 secreted from adipose tissue recruits macrophages and induces insulin
      resistance in mice.
AB  - AIMS/HYPOTHESIS: Obesity-induced inflammation is initiated by the recruitment of
      macrophages into adipose tissue. The recruited macrophages, called adipose tissue
      macrophages, secrete several proinflammatory cytokines that cause low-grade
      systemic inflammation and insulin resistance. The aim of this study was to find
      macrophage-recruiting factors that are thought to provide a crucial connection
      between obesity and insulin resistance. METHODS: We used chemotaxis assay,
      reverse phase HPLC and tandem MS analysis to find chemotactic factors from
      adipocytes. The expression of chemokines and macrophage markers was evaluated by
      quantitative RT-PCR, immunohistochemistry and FACS analysis. RESULTS: We report
      our finding that the chemokine (C-X-C motif) ligand 12 (CXCL12, also known as
      stromal cell-derived factor 1), identified from 3T3-L1 adipocyte conditioned
      medium, induces monocyte migration via its receptor chemokine (C-X-C motif)
      receptor 4 (CXCR4). Diet-induced obese mice demonstrated a robust increase of
      CXCL12 expression in white adipose tissue (WAT). Treatment of obese mice with a
      CXCR4 antagonist reduced macrophage accumulation and production of
      proinflammatory cytokines in WAT, and improved systemic insulin sensitivity.
      CONCLUSIONS/INTERPRETATION: In this study we found that CXCL12 is an adipocyte
      derived chemotactic factor that recruits macrophages, and that it is a required
      factor for the establishment of obesity-induced adipose tissue inflammation and
      systemic insulin resistance.

PMID- 24744123
TI  - Laparoscopic benefits to rare hernias: Invited comment to: Hesselbach's hernia
      after previous groin surgery, Wood et al. (2014) DOI 10.1007/s10029-013-1210-8.

PMID- 24744122
TI  - Prospective memory training in older adults and its relevance for successful
      aging.
AB  - In research on cognitive plasticity, two training approaches have been
      established: (1) training of strategies to improve performance in a given task
      (e.g., encoding strategies to improve episodic memory performance) and (2)
      training of basic cognitive processes (e.g., working memory, inhibition) that
      underlie a range of more complex cognitive tasks (e.g., planning) to improve both
      the training target and the complex transfer tasks. Strategy training aims to
      compensate or circumvent limitations in underlying processes, while process
      training attempts to augment or to restore these processes. Although research on
      both approaches has produced some promising findings, results are still
      heterogeneous and the impact of most training regimes for everyday life is
      unknown. We, therefore, discuss recent proposals of training regimes aiming to
      improve prospective memory (i.e., forming and realizing delayed intentions) as
      this type of complex cognition is highly relevant for independent living.
      Furthermore, prospective memory is associated with working memory and executive
      functions and age-related decline is widely reported. We review initial evidence
      suggesting that both training regimes (i.e., strategy and/or process training)
      can successfully be applied to improve prospective memory. Conceptual and
      methodological implications of the findings for research on age-related
      prospective memory and for training research in general are discussed. 

PMID- 24744124
TI  - Mitochondrial dysfunction in aging rat brain regions upon chlorpyrifos toxicity
      and cold stress: an interactive study.
AB  - Mitochondrial dysfunction and consequent energy depletion are the major causes of
      oxidative stress resulting to bring alterations in the ionic homeostasis causing
      loss of cellular integrity. Our previous studies have shown the age-associated
      interactive effects in rat central nervous system (CNS) upon co-exposure to
      chlorpyrifos (CPF) and cold stress leading to macromolecular oxidative damage.
      The present study elucidates a possible mechanism by which CPF and cold stress
      interaction cause(s) mitochondrial dysfunction in an age-related manner. In this
      study, the activity levels of Krebs cycle enzymes and electron transport chain
      (ETC) protein complexes were assessed in the isolated fraction of mitochondria.
      CPF and cold stress (15 and 20  degrees C) exposure either individually or in
      combination decreased the activity level of Krebs cycle enzymes and ETC protein
      complexes in discrete regions of rat CNS. The findings confirm that cold stress
      produces significant synergistic effect in CPF intoxicated aging rats. The
      synergism between CPF and cold stress at 15  degrees C caused a higher depletion
      of respiratory enzymes in comparison with CPF and cold stress alone and together
      at 20  degrees C indicating the extent of deleterious functional alterations in
      discrete regions of brain and spinal cord (SC) which may result in
      neurodegeneration and loss in neuronal metabolic control. Hence, co-exposure of
      CPF and cold stress is more dangerous than exposure of either alone. Among the
      discrete regions studied, the cerebellum and medulla oblongata appears to be the
      most susceptible regions when compared to cortex and SC. Furthermore, the study
      reveals a gradual decrease in sensitivity to CPF toxicity as the rat matures.

PMID- 24744125
TI  - Hypothalamic subependymal niche: a novel site of the adult neurogenesis.
AB  - The discovery of undifferentiated, actively proliferating neural stem cells
      (NSCs) in the mature brain opened a brand new chapter in the contemporary
      neuroscience. Adult neurogenesis appears to occur in specific brain regions
      (including hypothalamus) throughout vertebrates' life, being considered an
      important player in the processes of memory, learning, and neural plasticity. In
      the adult mammalian brain, NSCs are located mainly in the subgranular zone (SGZ)
      of the hippocampal dentate gyrus and in the subventricular zone (SVZ) of the
      lateral ventricle ependymal wall. Besides these classical regions, hypothalamic
      neurogenesis occurring mainly along and beneath the third ventricle wall seems to
      be especially well documented. Neurogenic zones in SGZ, SVZ, and in the
      hypothalamus share some particular common features like similar cellular
      cytoarchitecture, vascularization pattern, and extracellular matrix properties.
      Hypothalamic neurogenic niche is formed mainly by four special types of radial
      glia-like tanycytes. They are characterized by distinct expression of some neural
      progenitor and stem cell markers. Moreover, there are numerous suggestions that
      newborn hypothalamic neurons have a significant ability to integrate into the
      local neural pathways and to play important physiological roles, especially in
      the energy balance regulation. Newly formed neurons in the hypothalamus can
      synthesize and release food intake regulating neuropeptides and they are
      sensitive to the leptin. On the other hand, high-fat diet positively influences
      hypothalamic neurogenesis in rodents. The nature of this intriguing new site of
      adult neurogenesis is still so far poorly studied and requires further
      investigations. 

PMID- 24744126
TI  - Intraoperative detection and localization of cylindrical implants in cone-beam CT
      image data.
AB  - PURPOSE: Orthopedic fractures are often fixed using metal implants. The correct
      positioning of cylindrical implants such as surgical screws, rods and guide wires
      is highly important. Intraoperative 3D imaging is often used to ensure proper
      implant placement. However, 3D image interaction is time-consuming and requires
      experience. We developed an automatic method that simplifies and accelerates
      location assessment of cylindrical implants in 3D images. METHODS: Our approach
      is composed of three major steps. At first, cylindrical characteristics are
      detected by analyzing image gradients in small image regions. Next, these
      characteristics are grouped in a cluster analysis. The clusters represent
      cylindrical implants and are used to initialize a cylinder-to-image registration.
      Finally, the two end points are optimized regarding image contrast along the
      cylinder axis. RESULTS: A total of 67 images containing 420 cylindrical implants
      were used for testing. Different anatomical regions (calcaneus, spine) and
      various image sources (two mobile devices, three reconstruction methods) were
      investigated. Depending on the evaluation set, the detection performance was
      between 91.7 and 96.1% true- positive rate with a false-positive rate between 2.0
      and 3.2%. The end point distance errors ranged from [Formula: see text] to
      [Formula: see text] mm and the orientation errors from [Formula: see text] to
      [Formula: see text] degrees. The average computation time was less than 5
      seconds. CONCLUSIONS: An automatic method was developed and tested that obviates
      the need for 3D image interaction during intraoperative assessment of cylindrical
      orthopedic implants. The required time for working with the viewing software of
      cone-beam CT device is drastically reduced and leads to a shorter time under
      anesthesia for the patient.

PMID- 24744127
TI  - Effect of season and habitat on PCB bioaccumulation by caged bluegill sunfish
      deployed in a Great Lakes area of concern.
AB  - Bluegill sunfish were caged in the Detroit River, Ontario, Canada, for 64 days to
      determine bioaccumulation rates of PCBs. Deployments involved placing fish in
      cages suspended in the water (suspended cages) compared to cages partially buried
      in sediments. Deployments were performed in the summer and winter months. During
      summer, fish exhibited significant increases in body weight and lipid content
      (sediment associated cages only), whereas in winter, body weights did not change.
      Lipid normalized PCB concentrations and PCB mass in fish increased significantly
      with time in summer deployments, but not in winter. Fish continued to accumulate
      PCBs over the 64 days caging duration except for PCBs 33, 49, and 52 in sediment
      associated cages. There were no significant differences in the bioaccumulation of
      PCBs between cage types. This study confirms that biomonitoring studies using
      caged fish should ensure chemical toxicokinetics are consistent when comparing
      bioaccumulation results among sites and/or time points.

PMID- 24744128
TI  - Proteome array identification of bioactive soluble proteins/peptides in Matrigel:
      relevance to stem cell responses.
AB  - Matrigel and similar commercial products are extracts of the Engelbreth-Holm
      Swarm sarcoma that provide a basement-membrane-like attachment substrate or gel
      that is used to grow cells on or in, respectively. To ascertain further what
      proteins may be present in Matrigel, besides its major basement-membrane
      constituents, an analysis of the expressed liquid of gelled Matrigel was
      performed using proteome array technology. Among the growth factors/cytokines
      assayed, high positive detection was found for IGFBP1, IGFBP3, LIF, platelet
      factor 4, PlGF-2, and VEGF; moderate reactivity was found for cyr61, IGFBP2,
      IGFBP6, IL-1ra, and NOV; and low, but detectable, responses occurred for aFGF, IL
      13, IL-23, M-CSF, and VEGF-B. Among the chemokines assayed, high positive
      detection was found for MIG and serpin E1; moderate reactivity was found for IP
      10, MCP-1, and MCP-5, and low, but detectable, responses occurred for CXCL16, I
      TAC, and MIP-1alpha. Among the other biologically active proteins assayed, high
      positive detection was found for adiponectin, C5a, endocan, lipocalin-2, sICAM-1,
      MMP-3, and TIMP-1; moderate reactivity was found for C-reactive protein,
      coagulation factor III, endoglin, endostatin/collagen XVIII, endothelin-1, ICAM
      1, MMP-9, osteopontin, pentraxin-3, and RANTES; and low, but detectable,
      responses occurred for fetuin A, MMP-8, pentraxin-2, RBP4, resistin, and TIMP-4.
      The study found several growth factors, chemokines, and biologically active
      proteins not previously identified in Matrigel, and this may have significance to
      the interpretations of observed cellular responses when cells are grown on or in
      Matrigel. 

PMID- 24744130
TI  - Can an integrated orthotic and rehabilitation program decrease pain and improve
      function after lower extremity trauma?
AB  - BACKGROUND: Patients with severe lower extremity trauma have significant
      disability 2 years after injury that worsens by 7 years. Up to 15% seek late
      amputation. Recently, an energy-storing orthosis demonstrated improved function
      compared with standard orthoses; however, the effect when integrated with
      rehabilitation over time is unknown. QUESTIONS/PURPOSES: (1) Does an 8-week
      integrated orthotic and rehabilitation initiative improve physical performance,
      pain, and outcomes in patients with lower extremity functional deficits or pain?
      (2) Is the magnitude of recovery different if enrolled more than 2 years after
      their injury versus earlier? (3) Does participation decrease the number
      considering late amputation? METHODS: We prospectively evaluated 84 service
      members (53 less than and 31 > 2 years after injury) who enrolled in the
      initiative. Fifty-eight sustained fractures, 53 sustained nerve injuries with
      weakness, and six had arthritis (there was some overlap in the patients with
      fractures and nerve injuries, which resulted in a total of > 84). They completed
      4 weeks of physical therapy without the orthosis followed by 4 weeks with it.
      Testing was conducted at Weeks 0, 4, and 8. Validated physical performance tests
      and patient-reported outcome surveys were used as well as questions pertaining to
      whether patients were considering an amputation. RESULTS: By 8 weeks, patients
      improved in all physical performance measures and all relevant patient-reported
      outcomes. Patients less than and greater than 2 years after injury improved
      similarly. Forty-one of 50 patients initially considering amputation favored limb
      salvage at the end of 8 weeks. CONCLUSIONS: We found this integrated orthotic and
      rehabilitation initiative improved physical performance, pain, and patient
      reported outcomes in patients with severe, traumatic lower extremity deficits and
      that these improvements were sustained for > 2 years after injury. Efforts are
      underway to determine whether the Return to Run clinical pathway with the
      Intrepid Dynamic Exoskeletal Orthosis (IDEO) can be successfully implemented at
      additional military centers in patients > 2 years from injury while sustaining
      similar improvements in patient outcomes. The ability to translate this
      integrated orthotic and rehabilitation program into the civilian setting is
      unknown and warrants further investigation.

PMID- 24744129
TI  - The methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and tumor
      risk: evidence from 134 case-control studies.
AB  - Methylenetetrahydrofolate reductase (MTHFR) is an important enzyme involved in
      folate metabolism, which is essential for DNA synthesis and methylation. Genetic
      variations in the MTHFR gene seem to contribute to a decreased activity of MTHFR,
      ultimately confer increased susceptibility to cancer. As the most extensively
      studied polymorphism, MTHFR C677T polymorphism was shown to contribute to cancer
      susceptibility but the results were inconsistent. The authors performed a meta
      analysis including 134 studies (46,207 cases and 69,160 controls) to address the
      issue. Odds ratios (ORs) with corresponding 95% confidence intervals (CIs) were
      used to assess the association. Overall, a significant elevated risk of cancer
      was associated with the MTHFR C677T polymorphism in T-allele versus C-allele
      comparison (OR = 1.06, 95% CI 1.02-1.11, P(heterogeneity) < 0.001), homozygote
      model (OR = 1.08, 95% CI 1.01-1.17, P(heterogeneity) < 0.001) and dominant model
      (OR = 1.05, 95% CI 1.00-1.10, P(heterogeneity) < 0.001). In the stratified
      analyses, significantly increased cancer risks were indicated among Asians in all
      genetic models except for heterozygote model. Further analysis revealed that
      C677T was significantly associated with an increased risk of esophageal and
      stomach cancer. This meta-analysis supports an association between the MTHFR
      C677T polymorphism and increased risk of esophageal and stomach cancer,
      especially among Asians. Additionally, more high-quality studies and that the
      covariates responsible for heterogeneity should be controlled to obtain a more
      conclusive response about the function of MTHFR C677T in cancer.

PMID- 24744131
TI  - Systemic inflammatory markers and aspiration cell count may not differentiate
      bacterial from fungal prosthetic infections.
AB  - BACKGROUND: Fungal periprosthetic joint infections (PJIs) are rare. Fewer than
      200 cases have been reported in the literature. The characteristics of systemic
      inflammatory markers and joint aspirate cell count analysis obtained in patients
      with fungal PJIs have not been fully assessed. The ability to diagnose
      involvement of fungal PJI preoperatively may optimize the surgical and medical
      management of these patients. QUESTIONS/PURPOSES: We determined whether
      preoperative systemic inflammatory markers and total synovial fluid leukocyte
      count and neutrophil percentage were different between patients with fungal and
      bacterial PJI. METHODS: We reviewed the medical records of 44 patients with
      culture-positive diagnosed fungal PJIs treated at our institution between January
      1, 2002, and December 31, 2011, in this study. This represented 1.2% of the total
      3822 PJIs treated at our institution during the study period. The mean values for
      C-reactive protein, erythrocyte sedimentation rate, leukocyte count, and
      neutrophil percentage of patients with purely fungal PJIs were compared to those
      of 59 patients with bacterial PJIs treated by one surgeon during the same time
      period. RESULTS: The mean erythrocyte sedimentation rate values for fungal and
      bacterial PJIs were 40 mm/hour (95% CI: 30, 50 mm/hour) and 41 mm/hour (95% CI:
      33, 49 mm/hour), respectively (p=0.61). The mean C-reactive protein values for
      fungal and bacterial PJIs were 42 mg/L (95% CI: 22, 62 mg/L) and 65 mg/L (95% CI:
      43, 88 mg/L), respectively (p=0.42). The mean total nucleated leukocyte counts
      for fungal and bacterial PJIs were 11,928 (95% CI: 3906, 19,950) with 81% (95%
      CI: 75%, 88%) neutrophils and 36,901 (95% CI: 21,822, 51,921) with 73% (95% CI:
      65%, 81%) neutrophils, respectively (leukocyte count: p=0.19; neutrophil
      percentage: p=0.55). CONCLUSIONS: Early detection of fungal PJI is needed, but
      systemic inflammatory markers and synovial fluid cell count analyses from
      aspirations do not discriminate whether an infection may be of fungal origin.
      LEVEL OF EVIDENCE: Level IV, diagnostic study. See Instructions for Authors for a
      complete description of levels of evidence.

PMID- 24744132
TI  - Do jumbo cups cause hip center elevation in revision THA? A radiographic
      evaluation.
AB  - BACKGROUND: Acetabular revision THA with use of a large (jumbo) cup is an
      effective treatment for many cavitary and segmental peripheral bone defects.
      However, hip center elevation may occur with use of a jumbo cup owing to reaming
      superiorly and/or because of the increased diameter of the jumbo cup compared
      with the native acetabulum. QUESTIONS/PURPOSES: In our jumbo cup revision THAs,
      we attempted to avoid hip center elevation by placing the inferior edge of the
      cup at the inferior acetabulum. In this study, we asked (1) how much of an
      elevation in the hip center is observed radiographically with use of jumbo cups,
      and (2) how effective was our technique in minimizing hip center elevation during
      revision THA in clinical practice? METHODS: We retrospectively reviewed
      radiographic data for all patients, from one surgeon's practice, who received a
      jumbo cup (defined as cup size >= 66 mm in men, >= 62 mm in women) during an
      acetabular revision between 1998 and 2012 and who had an anatomically placed THA
      or no THA on the contralateral side (so as to be able to make comparisons); 98
      patients were identified and included. The height of the revised hip center was
      measured relative to the contralateral normal hip. Cup elevation resulting from
      superior reaming was determined by measuring the distance from the inferior cup
      edge to the interteardrop line. The mean hip center elevation and cup position
      relative to the interteardrop line in male and female patients were compared
      using unpaired t-tests. RESULTS: Radiographic analysis showed a mean hip center
      elevation of 11 mm. On average, 1 mm of the measured hip center elevation was the
      result of cup placement superior to its planned position at the interteardop
      line. CONCLUSIONS: Our results indicate that revision THA with a jumbo cup is
      associated with hip center elevation despite placement of the cup at the inferior
      acetabulum. An increase in femoral head length may be needed to compensate for
      hip center elevation with use of a jumbo cup. LEVEL OF EVIDENCE: Level III,
      therapeutic study. See the Instructions for Authors for a complete description of
      levels of evidence.

PMID- 24744133
TI  - Changes in inflammatory, coagulopathic, and fibrinolytic responses after
      endovascular repair of an abdominal aortic aneurysm: relationship between
      fibrinogen degradation product levels and endoleaks.
AB  - PURPOSE: To compare the inflammatory, coagulopathic, and fibrinolytic responses
      after endovascular aneurysm repair (EVAR) of an abdominal aortic aneurysm between
      two stent grafts. Fibrinogen degradation product (FDP) levels were compared
      between patients with or without an endoleak. MATERIALS AND METHODS: EVAR was
      performed in 88 patients using an Excluder (37 patients) or a Zenith (51
      patients). White blood cell count (WBC), C-reactive protein (CRP) levels,
      platelet count, and FDP levels were measured before and after EVAR. RESULTS: WBC
      and CRP increased and the platelet count decreased significantly on days 1 and 3
      after EVAR in the Zenith group compared with the Excluder group. The change in
      FDP from baseline to 7 days after EVAR was -1.99 +/- 7.46 vs. 8.59 +/- 9.38
      MUg/mL in patients with (n = 24) vs. without (n = 64) an endoleak (p < 0.001). A
      change in FDP of 3.1 MUg/mL was the optimal cutoff point for predicting the
      presence of an endoleak (accuracy 0.762; sensitivity 0.875; specificity 0.717).
      CONCLUSION: Inflammatory, coagulopathic, and fibrinolytic responses were greater
      in the Zenith group than in the Excluder group. A change in FDP of <=3.1 MUg/mL
      was predictive of an endoleak after EVAR.

PMID- 24744134
TI  - A case of gastric plexiform fibromyxoma: radiological and pathological findings.
AB  - Plexiform fibromyxoma is a relatively new pathological category that consists of
      a rare group of non-gastrointestinal stromal tumors with a peculiar plexiform
      growth pattern. We report a case of gastric plexiform fibromyxoma in a 60-year
      old man. Gastroscopic examination revealed a gastric submucosal tumor in the
      antrum. Magnetic resonance imaging (MRI) showed a nodule with distinct signal
      hyperintensity on T2-weighted images, with strong enhancement peripherally in the
      early phase to the entire lesion in the delayed phase. Endoscopic ultrasound
      guided fine-needle aspiration cytology was performed, and the cytological
      diagnosis was spindle cell tumor, so partial gastrectomy was performed under a
      preoperative diagnosis of GIST. The resected tumor demonstrated plexiform
      architecture, myxoid stroma, prominent vasculature, and spindle cells, reflecting
      the characteristic findings on MRI. This is the first report to describe
      radiological findings for gastric plexiform fibromyxoma.

PMID- 24744135
TI  - Present and future role of FDG-PET/CT imaging in the management of gynecologic
      malignancies.
AB  - Integrated positron emission tomography/computed tomography (PET/CT) with 2
      [18F]fluoro-2-deoxy-D-glucose (FDG) is a useful technique for acquiring both
      glucose metabolic and anatomic imaging data using a single device in a single
      diagnostic session, and has opened up a new field of clinical oncologic imaging.
      FDG-PET/CT has been used successfully for the staging, treatment optimization, re
      staging, therapy monitoring, and prognostication of uterine and ovarian cancers
      as well as various malignant tumors. The present review discusses the current
      role of FDG-PET/CT in the management of gynecologic malignancies, focusing on its
      usefulness and limitations for imaging such patients. 

PMID- 24744136
TI  - Persistent hypoglossal artery aneurysm located in the hypoglossal canal with
      associated subarachnoid hemorrhage.
AB  - The hypoglossal artery is one of four primitive anastomoses between the internal
      carotid artery and vertebrobasilar system that regresses in the sixth week of
      fetal development. A persistent hypoglossal artery (PHA) is generally an
      incidental finding but may also be associated with aneurysms or arteriovenous
      malformations. We present a rare case of a PHA with an associated bleeding
      intracranial PHA aneurysm located in the hypoglossal canal. 

PMID- 24744137
TI  - Navigational area of the cranio-orbital foramen and its significance in orbital
      surgery.
AB  - The cranio-orbital foramen (COF) is located on the lateral wall of the orbit. It
      is a potential source of hemorrhage during deep lateral orbital dissection, since
      it functions as an anastomosis between the lacrimal artery and the middle
      meningeal artery. The aim of this study was to guide and facilitate the surgical
      procedures in the orbit, so as to determine a navigational area and the precise
      location of the COF and to standardize certain anatomical marks. The navigational
      area of the COF and topographical features were studied in 75 craniums with
      presented COF. 33 bilateral main COFs, 41 (18 on the right, 23 on the left)
      unilateral main COFs at the main cranium and 19 accessory COFs were studied for
      their navigational features on the orbit. The distances between the COF and the
      fronto-zygomatic suture, supraorbital notch, lateral angle of the superior
      orbital fissure (SOF) and Whitnall's tubercle were measured. The mean distance of
      the COF from the fronto-zygomatic suture, supraorbital notch, lateral angle of
      the SOF and Whitnall's tubercle was 26.3, 37.3, 92 and 27.1 mm, respectively. For
      the navigational area signs of the COF, areas of the orbit that form the
      transversal and vertical lines are generated on the reference points. Whilst the
      upper outer area of the orbit contains a potential bleeding risk, the bottom
      section of the outer column is identified as safe for the surgical operations of
      the lateral orbital wall. The fronto-zygomatic suture and Whitnall's tubercle are
      recommended as the most reliable navigational landmarks for identifying the COF.
      Hence, the transversal and vertical orientation of the COF should be mastered by
      the surgeons reconstructing the anterior base of the skull and the orbit. 

PMID- 24744138
TI  - Sulcal and gyral anatomy of the basal occipital-temporal lobe.
AB  - PURPOSE: The sulcal and gyral anatomy of the basal occipital-temporal lobe is
      highly variable and detailed descriptions of this region are limited and often
      inconsistent. The aim of this study was to describe the salient features of the
      sulcal and gyral anatomy of the basal occipital-temporal lobe. METHODS: We
      studied the sulcal and gyral patterns of 30 formalin-fixed cerebral hemispheres.
      RESULTS: The major landmarks are the collateral sulcus (separated into the
      rhinal, proper, and caudal segments) and occipitotemporal sulcus (often
      interrupted), which were always present in this study. The bifurcation of the
      caudal collateral sulcus is a useful landmark. In relation to these sulci, we
      have described the surface anatomy and nominated landmarks of the medial
      (parahippocampal and lingual) and lateral (fusiform) occipitotemporal gyri.
      CONCLUSIONS: Understanding of the sulcal and gyral patterns of the basal
      occipital-temporal lobe may provide valuable information in its radiological and
      intraoperative interpretation.

PMID- 24744139
TI  - Strategies for the construction of tetrahydropyran rings in the synthesis of
      natural products.
AB  - This review focuses on the methodology used for the construction of
      tetrahydropyran (THP) rings in the synthesis of natural products over the last
      seven years. While methods like cyclisation onto oxocarbenium ions, reduction of
      cyclic hemi-ketals, Michael reactions, hetero-Diels-Alder cycloadditions and
      cyclisations onto epoxides continue to find application, several other strategies
      including metal-mediated cyclisations, ring-closing metathesis, radical
      cyclisations and carbocation cyclisations have also found use. This review is
      intended to provide an overview of the area for those who are unfamiliar, and to
      refresh and remind those who do work in the area of the exciting developments in
      the field. 

PMID- 24744140
TI  - Analysis of Growth Curves in Children After Adenotonsillectomy.
AB  - IMPORTANCE: Several studies have documented that children gain more weight than
      expected after adenotonsillectomy. OBJECTIVES: To examine patterns of change in
      weight and stature percentiles in children after adenotonsillectomy and to
      analyze clinical and demographic correlates of shifts in the growth curve.
      DESIGN, SETTING, AND PARTICIPANTS: In this retrospective medical record review,
      we studied patients 18 years and younger who underwent adenotonsillectomy at an
      academic pediatric tertiary medical center and had at least one height and weight
      measurement recorded at each of the following time points: within 3 months before
      surgery, within 3 to 9 months after surgery, and within 12 to 27 months after
      surgery. Data were procured from all children from January 1, 2007, through
      October 31, 2012, and initially included 2893 surgical patients and 161,458
      height and weight measurements. The final database consisted of 815 patients with
      adequate growth data and multiple time points. Logistic regression analysis was
      performed to examine patient age at surgery, preoperative weight, sex, and ethnic
      background for correlations with changes in weight, height, and body mass index
      percentiles. MAIN OUTCOMES AND MEASURES: Change in weight, height, and body mass
      index percentile before and after surgery. RESULTS: At 18 months after surgery,
      weight percentiles in the study group increased by a mean of 6.3 percentile
      points (P < .001). Body mass index percentiles increased by a mean of 8.0
      percentile points (P < .001). The greatest increases in weight percentiles were
      observed in children who were between the 1st and 60th percentiles for weight (P
      < .001) and younger than 4 years at the time of surgery (P < .001). An increase
      in weight percentile was not observed in children who preoperatively were already
      above the 80th percentile in weight (P = .15). CONCLUSIONS AND RELEVANCE: Weight
      gain after adenotonsillectomy occurs primarily in patients who are smaller and
      younger at the time of surgery and does not correlate with increased rates of
      obesity.

PMID- 24744141
TI  - Does carbon dioxide pneumoperitoneum enhance wound metastases following
      laparoscopic abdominal tumor surgery? A meta-analysis of 20 randomized control
      studies.
AB  - The mechanisms involved in the development of wound metastasis following
      laparoscopic abdominal tumor surgery remain unclear. The aim of this study was to
      accurately assess whether the duration of carbon dioxide pneumoperitoneum (CDP)
      during laparoscopic abdominal tumor surgery enhances wound metastases. We
      conducted a systematic review of PubMed, Cochrane Library, and Embase through
      December 2013 to identify animal experiments comparing wound recurrence between
      laparoscopic and gasless laparoscopic procedures or open procedures. The outcome
      of interest was the number of animals with a wound tumor. Meta-regression was
      used to assess whether heterogeneity was explained by study level covariates
      (animal model, study size, CDP pressure, duration, and evaluated time). Twenty
      randomized control studies involving 1,229 animals were included. Wound
      recurrence was not significant in the laparoscopic surgery (LP) vs. gasless
      laparoscopic surgery (GLP) subgroups [odds ratio (OR), 2.23; 95 % confidence
      interval (CI), 0.90-5.55; P = 0.08) or the LP vs. laparotomy (LA) subgroups (OR,
      0.97; 95 % CI, 0.31-3.00; P = 0.08). Overall postoperative wound recurrence
      results were not significantly different between the study groups and controls
      (OR, 1.47; 95 % CI, 0.74-2.92; P = 0.28). A meta-regression analysis showed that
      the outcome was not correlated with the covariates (animal model: P = 0.82;
      evaluated time: P = 0.30; pressure of CDP: P = 0.12; duration time: P = 0.80).
      Current evidence suggests that CDP does not enhance wound metastases following
      laparoscopic abdominal tumor surgery. Additional large sample, well-designed,
      randomized, controlled trials are needed to further confirm whether CDP duration
      in laparoscopic abdominal tumor surgery significantly enhances wound recurrence.

PMID- 24744142
TI  - 7B7: a novel antibody directed against the Ku70/Ku80 heterodimer blocks invasion
      in pancreatic and lung cancer cells.
AB  - Development of more effective therapeutic strategies for cancers of high unmet
      need requires the continued discovery of disease-specific protein targets for
      therapeutic antibody targeting. In order to identify novel proteins associated
      with cancer cell invasion/metastasis, we present here an alternative to antibody
      targeting of cell surface proteins with an established role in invasion; our
      functional antibody screening approach involves the isolation and selection of
      MAbs that are primarily screened for their ability to inhibit tumour invasion. A
      clonal population of the Mia PaCa-2, a pancreatic ductal adenocarcinoma (PDAC)
      cell line, which displays a highly invasive phenotype, was used to generate MAbs
      with the objective of identifying membrane targets directly involved in cancer
      invasion. Selected MAb 7B7 can significantly reduce invasion in a dose-responsive
      manner in Mia PaCa-2 clone 3 and DLKP-M squamous lung carcinoma cells. Using
      immunoprecipitation and liquid chromatography-tandem mass spectrometry (LC-MS-MS)
      analysis, the target antigen of anti-invasive antibody, 7B7, was determined to be
      the heterodimeric Ku antigen, Ku70/80, a core protein composed of the Ku70 and
      Ku80 subunits which is involved in non-homologous end-joining (NHEJ) DNA repair.
      RNA interference-mediated knockdown of Ku70 and Ku80 resulted in a marked
      decrease in the invasive capacity of Mia PaCa-2 clone 3 and DLKP-M cells,
      indicating that Ku70/Ku80 is functionally involved in pancreatic and lung cancer
      invasion. Immunohistochemical analysis demonstrated Ku70/Ku80 immunoreactivity in
      37 PDAC tumours, indicating that this heterodimer is highly expressed in this
      aggressive cancer type. This study demonstrates that a functional MAb screening
      approach coupled with immunoprecipitation/proteomic analyses can be successfully
      applied to identify functional anti-invasive MAbs and potential novel targets for
      therapeutic antibody targeting. 

PMID- 24744143
TI  - Common genetic variants on FOXE1 contributes to thyroid cancer susceptibility:
      evidence based on 16 studies.
AB  - Genome-wide association studies have identified polymorphisms at chromosome
      9q22.23 as a new thyroid cancer (TC) susceptibility locus in populations of
      European descent. Since then, the relationship between three common variations
      (rs965513, rs1867277, and rs71369530) of FOXE1 and TC has been reported in
      various ethnic groups; however, the results have been inconclusive. To derive a
      more precise estimation of the relationship as well as to quantify the between
      study heterogeneity and potential bias, a meta-analysis including 120,258
      individuals from 16 studies was performed. An overall random-effect per-allele
      odds ratio (OR) of 1.74 (95 % confidence interval (95 % CI), 1.62-1.86, P<10(-5))
      and 1.62 (95 % CI, 1.50-1.76, P<10(-5)) was found for the rs965513 and rs1867277
      polymorphisms, respectively. In addition, we also detected significant
      association of FOXE1 polyalanine tract (rs71369530) with TC risk (OR=2.01; 95 %
      CI, 1.66-2.44, P<10(-5)). Significant associations were also detected under
      dominant and recessive genetic models. In the subgroup analysis by ethnicity,
      significantly increased risks were found for the rs965513 polymorphism among
      Caucasians (OR=1.79; 95 % CI, 1.69-1.91, P<10(-5)) and Asians (OR=1.42; 95 % CI,
      1.12-1.81, P=0.004). Ethnicity was identified as a potential source of between
      study heterogeneity for rs965513. When stratified by sample size, study design,
      histological types of TC, and radiation exposure status, significantly increased
      risks were found for the rs965513 polymorphism. This meta-analysis demonstrated
      that the three common variations on FOXE1 is a risk factor associated with
      increased TC susceptibility, but these associations vary in different ethnic
      populations.

PMID- 24744144
TI  - LDH5 overexpression is associated with poor survival in patients with solid
      tumors: a meta-analysis.
AB  - Lactate dehydrogenase 5 (LDH5) is believed to be particularly important and a
      reliable marker of malignancy. However, it is still controversial whether LDH5
      expression can be regarded as a prognostic factor for cancer patients. We
      reviewed the literature by performing an electronic database search via PubMed to
      identify eligible studies that assessed the impact of LDH5 as a cancer prognostic
      marker and its association with HIF-1alpha. Heterogeneity and publication bias
      were also assessed. A total of 12 literatures which included 1,892 cancer
      patients were combined in the final analysis. Meta-analysis revealed that LDH5
      overexpression was associated with an unfavorable overall survival (12 studies,
      1,597 patients; HR 1.59, 95 % CI 1.17-2.16) and disease/recurrence/progression
      free survival (7 studies; 1,086 patients; HR 1.46, 95 % CI 1.04-2.04) among solid
      tumor patients. Meta-analysis revealed an association between the expression of
      LDH5 and hypoxia-inducible factors 1 (OR 2.72, 95 % CI 1.66-4.45). Publication
      bias could not be excluded when investigating the association of LDH5 expression
      and overall survival. However, when we accounted for publication bias using the
      trim and fill method, the results remained significant (HR 1.435, 95 % CI 1.071
      1.923, P < 0.05) suggesting the stability of our results. Therefore, our study
      suggested that LDH5 overexpression had a poor prognosis value in cancer patients.
      The results of this meta-analysis suggest that high LDH5 expression is associated
      with HIF-1alpha and poor overall survival in cancer patients.

PMID- 24744145
TI  - Estrogen-related receptor gamma is an in vivo receptor of bisphenol A.
AB  - Bisphenol A (BPA) is an endocrine disruptor that displays estrogenic activity.
      Several reports suggest that BPA may have estrogen receptor-independent effects.
      In zebrafish, 50 MUM BPA exposure induces otic vesicle abnormalities, including
      otolith aggregation. The purpose of this study was to test if BPA action was
      mediated in vivo during zebrafish development by the orphan nuclear estrogen
      related receptor (ERR) gamma. Combining pharmacological and functional
      approaches, we demonstrate that the zebrafish ERRgamma mediates BPA-induced
      malformations in otoliths. Using different bisphenol derivatives, we show that
      different compounds can induce a similar otolith phenotype than BPA and that the
      binding affinity of these derivatives to the zebrafish ERRgamma correlates with
      their ability to induce otolith malformations. Morpholino knockdown of ERRgamma
      function suppresses the BPA effect on otoliths whereas overexpression of ERRgamma
      led to a BPA-like otolith phenotype. Moreover, a subphenotypical dose of BPA (1
      MUM) combined with ERRgamma overexpression led to a full-dose (50 MUM) BPA
      otolith phenotype. We therefore conclude that ERRgamma mediates the otic vesicle
      phenotype generated by BPA. Our results suggest that the range of pathways
      perturbed by this compound and its potential harmful effect are larger than
      expected.-Tohme, M., Prud'homme, S. M., Boulahtouf, A., Samarut, E., Brunet, F.,
      Bernard, L., Bourguet, W., Gibert, Y., Balaguer, P., Laudet, V. Estrogen-related
      receptor gamma is an in vivo receptor of bisphenol A. 

PMID- 24744146
TI  - Human CD4+ HLA-G+ regulatory T cells are potent suppressors of graft-versus-host
      disease in vivo.
AB  - CD4(+) T cells expressing the immunotolerizing molecule HLA-G have been described
      as a unique human thymus-derived regulatory T (tTreg) cell subset involved in
      immunoregulation and parenchymal homeostasis during infectious and autoimmune
      inflammation. We compared properties and molecular characteristics of human
      CD4(+)HLA-G(+) with those of CD4(+)CD25(+)FoxP3-expressing tTreg cells using in
      vitro studies of T-cell receptor (TCR) signaling, single-cell electrophysiology,
      and functional in vivo studies. Both tTreg populations are characterized by
      alterations in proximal-signaling pathways on TCR stimulation and a
      hyperpolarization of the plasma membrane when compared to conventional CD4(+) T
      cells. However, both clearly differ in phenotype and pattern of secreted
      cytokines, which results in distinct mechanisms of suppression: While CD4(+)HLA
      G(+) cells secrete high levels of inhibitory molecules (IL-10, soluble HLA-G, IL
      35), CD4(+)CD25(+)FoxP3(+) cells express these molecules at significantly lower
      levels and seem to exert their function mainly in a contact-dependent manner via
      cyclic adenosine-monophosphate. Finally we demonstrate that human CD4(+)HLA-G(+)
      tTreg cells significantly ameliorated graft-versus-host disease in a humanized
      mouse model as a first proof of their in vivo relevance. Our data further
      characterize and establish CD4(+)HLA-G(+) cells as a potent human tTreg
      population that can modulate polyclonal adaptive immune responses in vivo and
      thus being a promising candidate for potential clinical applications in the
      future.

PMID- 24744148
TI  - Tomosyn-2 is required for normal motor performance in mice and sustains
      neurotransmission at motor endplates.
AB  - Tomosyn-1 (STXBP5) is a soluble NSF attachment protein receptor complex-binding
      protein that inhibits vesicle fusion, but the role of tomosyn-2 (STXBP5L) in the
      mammalian nervous system is still unclear. Here we generated tomosyn-2 null
      (Tom2(KO/KO)) mice, which showed impaired motor performance. This was accompanied
      by synaptic changes at the neuromuscular junction, including enhanced spontaneous
      acetylcholine release frequency and faster depression of muscle motor endplate
      potentials during repetitive stimulation. The postsynaptic geometric arrangement
      and function of acetylcholine receptors were normal. We conclude that tomosyn-2
      supports motor performance by regulation of transmitter release willingness to
      sustain synaptic strength during high-frequency transmission, which makes this
      gene a candidate for involvement in neuromuscular disorders. 

PMID- 24744147
TI  - O-GlcNAcylation stabilizes beta-catenin through direct competition with
      phosphorylation at threonine 41.
AB  - Dysfunctions in Wnt signaling increase beta-catenin stability and are associated
      with cancers, including colorectal cancer. In addition, beta-catenin degradation
      is decreased by nutrient-dependent O-GlcNAcylation. Human colon tumors and colons
      from mice fed high-carbohydrate diets exhibited higher amounts of beta-catenin
      and O-GlcNAc relative to healthy tissues and mice fed a standard diet,
      respectively. Administration of the O-GlcNAcase inhibitor thiamet G to mice also
      increased colonic expression of beta-catenin. By ETD-MS/MS, we identified 4 O
      GlcNAcylation sites at the N terminus of beta-catenin (S23/T40/T41/T112).
      Furthermore, mutation of serine and threonine residues within the D box of beta
      catenin reduced O-GlcNAcylation by 75%. Interestingly, elevating O-GlcNAcylation
      in human colon cell lines drastically reduced phosphorylation at T41, a key
      residue of the D box responsible for beta-catenin stability. Analyses of beta
      catenin O-GlcNAcylation mutants reinforced T41 as the most crucial residue that
      controls the beta-catenin degradation rate. Finally, inhibiting O-GlcNAcylation
      decreased the beta-catenin/alpha-catenin interaction necessary for mucosa
      integrity, whereas O-GlcNAcase silencing improved this interaction. These results
      suggest that O-GlcNAcylation regulates not only the stability of beta-catenin,
      but also affects its localization at the level of adherens junctions.
      Accordingly, we propose that O-GlcNAcylation of beta-catenin is a missing link
      between the glucose metabolism deregulation observed in metabolic disorders and
      the development of cancer.

PMID- 24744149
TI  - Deletion of aquaporin-4 increases extracellular K(+) concentration during
      synaptic stimulation in mouse hippocampus.
AB  - The coupling between the water channel aquaporin-4 (AQP4) and K(+) transport has
      attracted much interest. In this study, we assessed the effect of Aqp4 deletion
      on activity-induced [K(+)]o changes in acute slices from hippocampus and corpus
      callosum of adult mice. We show that Aqp4 deletion has a layer-specific effect on
      [K(+)]o that precisely mirrors the known effect on extracellular volume dynamics.
      In CA1, the peak [K(+)]o in stratum radiatum during 20 Hz stimulation of Schaffer
      collateral/commissural fibers was significantly higher in Aqp4 (-/-) mice than in
      wild types, whereas no differences were observed throughout the [K(+)]o recovery
      phase. In stratum pyramidale and corpus callosum, neither peak [K(+)]o nor post
      stimulus [K(+)]o recovery was affected by Aqp4 deletion. Our data suggest that
      AQP4 modulates [K(+)]o during synaptic stimulation through its effect on
      extracellular space volume. 

PMID- 24744150
TI  - Childhood adversity, depression, age and gender effects on white matter
      microstructure: a DTI study.
AB  - Previous diffusion tensor imaging (DTI) studies have shown that various factors
      can affect white matter (WM) tract diffusivity. The aim of the present study was
      to investigate the effects of childhood adversity (CA), age and gender on WM
      diffusivity in tracts that are thought to be involved in emotional regulation in
      individuals with major depressive disorder (MDD) and healthy controls (HC). DTI
      was obtained from 46 subjects with MDD and 46 HC subjects. Data were pre
      processed and deterministic tractography was applied in the cingulum, uncinate
      fasciculus (UF), fornix, superior longitudinal fasciculus (SLF) and fronto
      occipital fasciculus (FOF). In subjects with a history of CA, fractional
      anisotropy (FA) was greater in the rostral cingulum (RC) and dorsal cingulum,
      whereas radial diffusivity (RD) was smaller in the RC when compared with subjects
      with no history of CA. In the UF, FOF and parahippocampal cingulum, FA was
      greater in the left hemisphere in the subjects with CA when compared with those
      without CA. Age affected FA, longitudinal diffusivity and RD in the UF, fornix,
      FOF and SLF, reflecting axonal and myelin degeneration with increasing age.
      Depression or gender did not have any effects on the diffusivity measures. Due to
      the cross-sectional nature of the study, a recall bias for CA and possible
      effects of medical treatment on diffusivity measures could have played a role. CA
      and age could increase the likelihood to develop WM microstructural anomalies in
      the brain affective network. Moreover, subjects with CA could be more vulnerable
      to FA changes. 

PMID- 24744151
TI  - The left inferior fronto-occipital fasciculus subserves language semantics: a
      multilevel lesion study.
AB  - Consequential works in cognitive neuroscience have led to the formulation of an
      interactive dual-stream model of language processing: the dorsal stream may
      process the phonological aspects of language, whereas the ventral stream may
      process the semantic aspects of language. While it is well-accepted that the
      dorsal route is subserved by the arcuate fasciculus, the structural connectivity
      of the semantic ventral stream is a matter of dispute. Here we designed a
      longitudinal study to gain new insights into this central but controversial
      question. Thirty-one patients harboring a left diffuse low-grade glioma-a rare
      neurological condition that infiltrates preferentially white matter associative
      pathways-were assessed with a prototypical task of language (i.e. verbal fluency)
      before and after surgery. All were operated under local anesthesia with a
      cortical and subcortical brain mapping-enabling to identify and preserve eloquent
      structures for language. We performed voxel-based lesion-symptom (VLSM) analyses
      on pre- and postoperative behavioral data. Preoperatively, we found a significant
      relationship between semantic fluency scores and the white matter fibers shaping
      the ventro-lateral connectivity (P < 0.05 corrected). The statistical map was
      found to substantially overlap with the spatial position of the inferior fronto
      occipital fasciculus (IFOF) (37.7%). Furthermore, a negative correlation was
      observed between semantic fluency scores and the infiltration volumes in this
      fasciculus (r = -0.4, P = 0.029). Postoperatively, VLSM analyses were
      inconclusive. Taken as a whole and when combined with the literature data, our
      findings strengthen the view that the IFOF plays an essential role in semantic
      processing and may subserve the direct ventral pathway of language.

PMID- 24744152
TI  - Short-interval lower-dose intravenous cyclophosphamide as induction and
      maintenance therapy for lupus nephritis: a prospective observational study.
AB  - Cyclophosphamide (CYC) has long been considered a gold standard in inducing renal
      remission and preventing renal flares for patients with systemic lupus
      erythematosus (SLE). However, the rational use of CYC has not reached a
      consensus, such as the timing and length of treatment, the route of
      administration, and the ideal dosage. The objective of this study was to assess
      the efficacy and safety of short-interval lower-dose (SILD) intravenous (IV) CYC
      in the treatment of SLE. A total of 225 patients with lupus nephritis were
      randomly assigned to a 1-year trial, either the SILD group (12 fortnightly pulses
      at a fixed dose of 400 mg followed by 6 monthly pulses) or high-dose (HD) group
      (6 monthly pulses followed by two quarterly pulses at a dose of 0.5~1.0 g/m(2)).
      At 6 months of treatment, 28 % (30/107) of patients in the SILD group reached a
      complete remission (CR), and 51.4 % (55/107) were in partial remission (PR), as
      compared with 32.7 % (35/107) and 45.8 % (49/107) in the HD group, respectively.
      Serum albumin, 24-h urinary protein, and the scores of disease activity were
      significantly improved in both groups at 6 months and maintained at the end of
      clinical trial. However, the SILD group showed much less menstrual disturbances
      (11.5 %), gastrointestinal adverse effects (5.3 %), and leukopenia (9.7 %) than
      the HD group (28.6, 26.8, and 19.8 %, respectively) at the end of clinical trial.
      The efficacy of the short-interval lower-dose (SILD) IV CYC regimen in the
      treatment of lupus nephritis is equivalent to that of the high-dose (HD) regimen,
      whereas the incidence of adverse events is much lower in the SILD group. 

PMID- 24744153
TI  - Health care in systemic lupus erythematosus (SLE): the patient's perspective.
AB  - In order to provide more patient-centered care for patients suffering from
      systemic lupus erythematosus (SLE), we studied their current satisfaction and
      preferences regarding future health care delivery. We sent questionnaires to all
      SLE patients visiting the rheumatology outpatient clinic in Leiden, the
      Netherlands. The questionnaire comprised three topics: (a) health care needs
      using a modified version of SLE Needs Questionnaire (range 0-38), (b)
      satisfaction with care per provider (visual analogue scale, range 0 (not at all)
      100 (very satisfied)), and (c) preferences for future healthcare (four items).
      One hundred and two patients (63 % response) reported an average of 16 (+/-6)
      health care needs, with all patients reporting a need in the physical domain.
      More needs were significantly associated with worse physical functioning and a
      higher educational level. The average satisfaction score was 73 (+/-19) with a
      lower overall satisfaction score being associated with younger age and an
      educational level higher or lower than average. Regarding preferences for future
      health care delivery, 75 % of patients showed interest in a yearly standardized
      medical assessment, 57 % in regular, specialized nurse contacts using internet,
      50 % in a yearly inventory on the need for self-management support, and 36 % in
      an education course. The association of age, education level and physical
      functioning with health care needs, and/or satisfaction suggest that the delivery
      of care should be better tailored to the needs of subgroups of patients.

PMID- 24744154
TI  - The application of dual-energy computed tomography in the diagnosis of acute
      gouty arthritis.
AB  - The aim of the study was to investigate the sensitivity and specificity of dual
      energy computed tomography in the diagnosis of acute gouty arthritis, and the
      related risk factors for urate crystal deposition. One hundred ninety-one
      patients (143 with acute gouty arthritis and 48 with other arthritic conditions)
      were studied. All patients had acute arthritic attack in the recent 15 days and
      underwent dual-energy computed tomography (DECT) scan with the affected joints.
      The urate volume was calculated by DECT and the basic information of these
      patients was recorded at the same time. Uric acid crystals were identified with
      DECT in 140 of 143 (97.9 %) gout patients and 6 of 48 (12.5 %) of nongout
      patients, respectively. The sensitivity, specificity, positive predictive value,
      and negative predictive value of DECT in the diagnosis of acute gouty arthritis
      were 97.9, 87.5, 95.9, and 93.3 %, respectively. The urate volumes were ranged
      from 0.57 to 54,543.27 mm(3) with a mean volume of 1,787.81 +/- 7,181.54 mm(3).
      Interestingly, urate volume was correlated with the disease duration, serum uric
      acid levels, the presence of tophi, and bone erosion. Two-year follow-up data was
      available in one patient with recurrent gouty arthritis, whose urate volume was
      gradually reduced in size by DECT detection after urate-lowering therapies. DECT
      showed high sensitivity and specificity for the identification of urate crystals
      and diagnosis of acute gout. The risk factors for uric acid deposition include
      the disease duration, serum uric acid levels, the presence of tophi, and bone
      erosion. DECT has an important role in the differential diagnosis of arthritis,
      and also could be served as a follow-up tool. 

PMID- 24744155
TI  - Is pain the only symptom in patients with benign joint hypermobility syndrome?
AB  - The aims of this study were to evaluate pain, depression level, fatigue, sleep,
      and quality of life (QoL) among patients with benign joint hypermobility syndrome
      (BJHS) and to compare their results with those of healthy controls. The study
      involved 115 patients and 114 healthy volunteers. Pain level was rated using
      visual analogue scale (VAS) for all patients. Depression level, fatigue, sleep
      quality, and QoL of all the participants were evaluated by the Beck Depression
      Inventory (BDI), the Checklist Individual Strength (CIS), the Pittsburgh Sleep
      Quality Index (PSQI), and the Short Form-36 (SF-36), respectively. VAS value was
      6.29 +/- 0.94 in the patient group. Comparison of two groups showed that there
      were statistically significant differences between the patient group and the
      control group with respect to BDI, total CIS, PSQI scores, SF-36 subscales
      (physical function, role physical, bodily pain, general health, role emotional,
      and mental health), and mental component summary (p < 0.001). While pain is the
      predominant symptom among BJHS patients, depression, fatigue, impaired sleep, and
      QoL also commonly occur. Thus, all of these components should be taken into
      account when assessing patients with BJHS.

PMID- 24744156
TI  - Cytospin preparations are superior to common smears in the detection of
      monosodium urate crystals in low-cellular synovial fluids.
AB  - In cases of gout with a low synovial fluid (SF) leukocyte count and atypical
      clinical presentation, such as in intercritical periods, the load of monosodium
      urate (MSU) crystals is frequently low, and thus, methods to improve the crystal
      detection may be beneficial. We compared the MSU crystal detection rates between
      cytospin slides and common smear preparations in low-cellular (<2,000/MUl) SF
      samples of patients with gout. We determined the number of MSU crystals/15 high
      power fields (HPF) at * 1,000 magnification by polarised microscopy in cytospin
      preparations and smears in SF samples of 17 patients with MSU-crystal-proven gout
      and compared the two methods statistically. All of the cytospin slides (100 %)
      contained MSU crystals and showed a median number of 124 crystals/15 HPF (range 2
      3,915), whereas 5 of the 17 smears (29 %) were MSU-crystal-negative, with a
      median count of 2 crystals/15 HPF (range 0-430/HPF). The difference was
      statistically highly significant (p < 0.0001). In conclusion, we have shown that
      the cytospin technique is superior to smears in the detection of MSU crystals in
      SF with a low SF leukocyte count. In light of our observations, we recommend the
      use of cytocentrifuges for routine crystal analysis in such cases.

PMID- 24744157
TI  - Ascorbic acid and salicylic acid mitigate nacl stress in Caralluma tuberculata
      Calli.
AB  - Plants exposed to salt stress undergo biochemical and morphological changes even
      at cellular level. Such changes also include activation of antioxidant enzymes to
      scavenge reactive oxygen species, while morphological changes are determined as
      deformation of membranes and organelles. Present investigation substantiates this
      phenomenon for Caralluma tuberculata calli when exposed to NaCl stress at
      different concentrations. Elevated levels of superoxide dismutase (SOD),
      peroxidase (POD), catalase (CAT), ascorbate peroxidase (APX), and glutathione
      reductase (GR) in NaCl-stressed calli dwindled upon application of non-enzymatic
      antioxidants; ascorbic acid (AA) and salicylic acid (SA). Many fold increased
      enzymes concentrations trimmed down even below as present in the control calli.
      Electron microscopic images accentuated several cellular changes upon NaCl stress
      such as plasmolysed plasma membrane, disruption of nuclear membrane, increased
      numbers of nucleoli, alteration in shape and lamellar membrane system in plastid,
      and increased number of plastoglobuli. The cells retrieved their normal structure
      upon exposure to non-enzymatic antioxidants. The results of the present
      experiments conclude that NaCl aggravate oxidative molecules that eventually
      alleviate antioxidant enzymatic system. Furthermore, the salt stress knocked down
      by applying ascorbic acid and salicylic acid manifested by normal enzyme level
      and restoration of cellular structure. 

PMID- 24744158
TI  - Suppression of NF-kappaB by dieckol extracted from Ecklonia cava negatively
      regulates LPS induction of inducible nitric oxide synthase gene.
AB  - Dieckol, extracted from brown algae, Ecklonia cava, is suggested to elicit anti
      inflammatory or anti-tumorigenic activities. However, dieckol-mediated regulatory
      mechanism for inflammatory response still remains elusive. Here, we show that
      dieckol suppressed lipopolysaccharide (LPS)-induced inducible nitric oxide
      synthase (iNOS) expression in mouse leukemic macrophage Raw264.7 cells. Also,
      dieckol decreased LPS-induced both nitric oxide (NO) production and iNOS promoter
      driven transcriptional activity in a dose-dependent manner. On the other hand,
      LPS-mediated NF-kappaB activity was inhibited by dieckol treatment. Moreover,
      results revealed that dieckol diminished LPS-mediated p65 nuclear translocation
      or IkappaBalpha phosphorylation dose-dependently, and reduced LPS-induced
      phosphorylation of mitogen-activated protein kinases (MAPKs), significantly
      p38MAPK. Collectively, these findings suggest that dieckol acts as a negative
      regulator of LPS-mediated iNOS induction through suppression of NF-kappaB
      activity, implying a mechanistic role of dieckol in regulation of inflammatory
      response. 

PMID- 24744159
TI  - Development of hollow/porous floating beads of metoprolol for pulsatile drug
      delivery.
AB  - The purpose of this work was to develop hollow calcium pectinate beads for
      floating pulsatile release of metoprolol tartrate intended for
      chronopharmacotherapy. Floating pulsatile concept was applied to increase the
      gastric residence of the dosage form having lag phase followed by a burst
      release. To overcome limitations of various approaches for imparting buoyancy,
      hollow/porous beads were prepared by simple process of acid-base reaction during
      ionotropic cross-linking using low methoxy pectin, xanthan gum, sodium carboxy
      methyl cellulose, guar gum, locust bean, gellan gum and calcium chloride as a
      cross-linking agent. Based on the preliminary studies optimized polymers were
      selected for formulation design with different polymers ratio concentrations. The
      obtained floating beads were studied for entrapment efficiency, buoyancy study,
      swelling index, surface morphology, in vitro release, stability studies and in
      vivo floating study. The floating beads obtained were porous, float up to 12-24
      h. The radiological studies (X-rays) pointed out the capability of the system to
      release drug in lower parts of GIT after a programmed lag time for hypertension.
      The floating beads provided expected two-phase release pattern with initial lag
      time during floating in acidic medium followed by rapid pulse release in
      phosphate buffer. From the accelerated stability studies, it was observed that
      the formulations are quite stable. All formulations followed first-order release
      kinetics by diffusion mechanism. This approach suggested the use of hollow
      calcium pectinate microparticles as promising floating pulsatile drug delivery
      system for site- and time-specific release of drugs acting as per chronotherapy
      of diseases. 

PMID- 24744160
TI  - Single particle tracking reveals biphasic transport during nanorod
      magnetophoresis through extracellular matrix.
AB  - Magnetic drug targeting has been proposed as a means of efficiently targeting
      drugs to tumors. However, the extracellular matrix (ECM) remains a significant
      barrier to long-range magnetophoretic transport through the tumor volume. While
      ensemble measurements of nanoparticle magnetophoresis have been reported, a
      single particle level understanding of magnetophoretic transport remains at
      large. We quantify nanorod magnetophoresis through ECM based on single particle
      observations. We find that smaller diameter particles achieve larger velocities
      through ECM despite experiencing smaller magnetic forces. Additionally, two
      interesting dynamics are elucidated. First, 18 nm diameter nanorods experience
      bimodal stick-slip motion through ECM during static field magnetophoresis, while
      similar bimodal transport is not observed for 55 nm nor 200 nm diameter nanorods.
      Second, smaller particles experience larger deviations in their orientation angle
      with respect to the magnetic field. This work elucidates important dynamics of
      nanoparticle transport through complex, porous biomaterials that may go unnoticed
      during ensemble measurements. 

PMID- 24744161
TI  - Phase 1 dose escalation and pharmacokinetic evaluation of oral gemcitabine
      prodrug (LY2334737) in combination with docetaxel in patients with advanced solid
      tumors.
AB  - PURPOSE: This Phase 1 study aimed to determine the recommended Phase 2 dose of
      LY2334737, an oral gemcitabine prodrug, when combined with standard dose
      docetaxel treatment in patients with advanced solid tumors. Pharmacokinetics (PK)
      and antitumor activity were additionally evaluated. METHODS: Patients with
      advanced/metastatic solid tumors received escalating doses of LY2334737 once
      daily (QD) for 14 days, followed by a 7-day drug-free period. Docetaxel was given
      at 75 mg/m(2) every 3 weeks (q3w). Cycles were repeated until progressive disease
      (PD) or unacceptable toxicity. RESULTS: Of 22 patients recruited, all Caucasian,
      7 received an LY2334737 dose of 10 mg/day, 10 received 20 mg/day, 5 received 30
      mg/day. Nineteen patients discontinued due to PD, 2 due to adverse events, 1 due
      to investigator decision. Dose-limiting toxicities: 2* febrile neutropenia (G3),
      2* fatigue (1* G2, 1* G3), 1* neutropenia (G4). The maximum tolerated dose (MTD)
      was identified to be 10 mg/day. Two patients achieved partial response, 10
      patients stable disease. Enrollment was stopped after unexpected hepatic
      toxicities were observed with LY2334737 QD for 14 days per cycle in another study
      of Japanese patients. PK data were consistent with the first-in-man study of
      LY2334737 and did not reveal any drug-drug interaction between LY2334737 and
      docetaxel. CONCLUSIONS: Combination of LY2334737 at doses up to 30 mg/day QD for
      14 days per cycle with docetaxel 75 mg/m(2) q3w resulted in an undesirable
      toxicity profile and a low MTD of 10 mg/day. Alternative treatment schedules of
      LY2334737 should be explored.

PMID- 24744162
TI  - Safety analysis of two different regimens of uracil-tegafur plus leucovorin as
      adjuvant chemotherapy for high-risk stage II and III colon cancer in a phase III
      trial comparing 6 with 18 months of treatment: JFMC33-0502 trial.
AB  - PURPOSE: The JFMC33-0502 trial is a phase III clinical study designed to
      determine the most appropriate duration of postoperative adjuvant chemotherapy
      with uracil-tegafur (UFT) plus leucovorin in patients with stage IIB or III colon
      cancer. We report the interim results of preplanned safety analyses. METHODS:
      Patients with stage IIB or III colon cancer who had undergone curative resection
      were randomly assigned to receive UFT (300 mg/m(2)) plus leucovorin (75 mg/day)
      for 6 months (control group, 4 weeks of treatment followed by a 1-week rest, five
      courses) or for 18 months (study group, 5 days of treatment followed by a 2-day
      rest, 15 courses). Treatment status and safety were evaluated. RESULTS: A total
      of 1,071 patients were enrolled, and 1,063 were included in safety analyses.
      Treatment completion rate at 6 months was 74.0 % in the control group and 76.7 %
      in the study group. Treatment completion rate in the study group at 18 months was
      56.0 %. The overall incidence of adverse events (AEs) was 75.3 % in the control
      group and 77.6 % in the study group. The incidences of grade 3 or higher AEs were
      low in both groups. During the first 6 months, the incidences of the subjective
      AEs were significantly lower in the study group. CONCLUSIONS: Oral UFT plus
      leucovorin given by either dosage schedule is a very safe regimen for adjuvant
      chemotherapy. In particular, 5 days of treatment followed by a 2-day rest was a
      useful treatment option from the viewpoint of toxicity even when given for longer
      than 6 months.

PMID- 24744163
TI  - The novel thymidylate synthase inhibitor trifluorothymidine (TFT) and TRAIL
      synergistically eradicate non-small cell lung cancer cells.
AB  - PURPOSE: TRAIL, a tumor selective anticancer agent, may be used for the treatment
      of non-small cell lung cancer (NSCLC). However, TRAIL resistance is frequently
      encountered. Here, the combined use of TRAIL with trifluorothymidine (TFT), a
      thymidylate synthase inhibitor, was examined for sensitizing NSCLC cells to
      TRAIL. METHODS: Interactions between TRAIL and TFT were studied in NSCLC cells
      using growth inhibition and apoptosis assays. Western blotting and flow cytometry
      were used to investigate underlying mechanisms. RESULTS: The combined treatment
      of TFT and TRAIL showed synergistic cytotoxicity in A549, H292, H322 and H460
      cells. For synergistic activity, the sequence of administration was important;
      TFT treatment followed by TRAIL exposure did not show sensitization. Combined TFT
      and TRAIL treatment for 24 h followed by 48 h of TFT alone was synergistic in all
      cell lines, with combination index values below 0.9. The treatments affected cell
      cycle progression, with TRAIL inducing a G1 arrest and TFT, a G2/M arrest. TFT
      activated Chk2 and reduced Cdc25c levels known to cause G2/M arrest. TRAIL
      induced caspase-dependent apoptosis was enhanced by TFT, whereas TFT alone mainly
      induced caspase-independent death. TFT increased the expression of p53 and
      p21/WAF1, and p53 was involved in the increase of TRAIL-R2 surface expression.
      TFT also caused downregulation of cFLIP and XIAP and increased Bax expression.
      CONCLUSIONS: TFT enhances TRAIL-induced apoptosis in NSCLC cells by sensitizing
      the apoptotic machinery at different levels in the TRAIL pathway. Our findings
      suggest a possible therapeutic benefit of the combined use of TFT and TRAIL in
      NSCLC.

PMID- 24744164
TI  - Natural and synthetic biodegradable polymers: different scaffolds for cell
      expansion and tissue formation.
AB  - The formation of tissue produced by implanted cells is influenced greatly by the
      scaffold onto which they are seeded. In the long term it is often preferable to
      use a biodegradable material scaffold so that all the implanted materials will
      disappear, leaving behind only the generated tissue. Research in this area has
      identified several natural biodegradable materials. Among them, hydrogels are
      receiving increasing attention due to their ability to retain a great quantity of
      water, their good biocompatibility, their low interfacial tension, and the
      minimal mechanical and frictional irritation that they cause. Biocompatibility is
      not an intrinsic property of materials; rather it depends on the biological
      environment and the tolerability that exists with respect to specific polymer
      tissue interactions. The most often utilized biodegradable synthetic polymers for
      3D scaffolds in tissue engineering are saturated poly-a-hydroxy esters, including
      poly(lactic acid) (PLA) and poly(glycolic acid) (PGA), as well as poly(lactic-co
      lycolide) (PLGA) copolymers. Hard materials provide compressive and torsional
      strength; hydrogels and other soft composites more effectively promote cell
      expansion and tissue formation. This review focuses on the future potential for
      understanding the characteristics of the biomaterials considered evaluated for
      clinical use in order to repair or to replace a sizable defect by only harvesting
      a small tissue sample. 

PMID- 24744165
TI  - Calcium profiling in hemodiafiltration: a new way to reduce the calcium overload
      risk without compromising cardiovascular stability.
AB  - BACKGROUND: Low and high dialysate calcium (Ca2+) content may have positive and
      harmful effects depending on the considered pathological aspect: hemodynamic
      instability, cardiac arrhythmias, parathormone release, adynamic bone disease,
      cardio-vascular calcifications. We hypothesized that a time-profiled Ca2+
      concentration would keep the cardiovascular advantages of high Ca2+ but would
      reduce the risk of calcium overload. METHODS: A prospective, multicenter study
      using a particular hemodiafiltration technique that allows the profiling of
      electrolytes was designed. Patients (n = 22) underwent randomly a 3-week dialysis
      session with low and high constant dialysate Ca2+ (Ld(Ca,), 1.25 mM and Hd(Ca,),
      2 mM) and profiled Ca2+ (Pd(Ca)), respectively. Plasma and spent dialysate Ca2+,
      systolic and diastolic arterial pressure (SAP, DAP) and QT interval corrected for
      heart rate (QTc) were analyzed. RESULTS: Plasma Ca2+ concentration decreased in
      Ld(Ca), whereas it increased in Hd(Ca) and to a lesser extent, in Pd(Ca). Total
      amount of Ca2+ given to the patient in Pd(Ca) (15.5 +/- 1.0 mmol) was higher than
      in Ld(Ca) (4.3 +/- 1.6 mmol) but lower than in Hd(Ca) (21.9 +/- 3.3 mmol). SAP
      and DAP decreased in Ld(Ca), whereas it was almost constant in both Hd(Ca) and
      Pd(Ca.). QTc significantly increased, up to critical values (>460 msec), only
      during Ld(Ca.). CONCLUSIONS: Pd(Ca) seems to retain the advantages of high Ca2+
      in terms of hemodynamic stability and modification of QTc while reducing the
      excessive positive calcium balance typical of dialysis with high Ca2+ content.

PMID- 24744167
TI  - Endotoxin adsorbents in extracorporeal blood purification: do they fulfill
      expectations?
AB  - INTRODUCTION: Lipopolysaccharides (LPS) are extremely strong stimulators of
      inflammatory reactions, act at very low concentrations, and are involved in the
      pathogenesis of sepsis and septic shock. Because of its toxicity, the efficient
      removal of endotoxin from patients' blood is very important in clinical medicine.
      The purpose of this study was to determine the endotoxin adsorption capacities of
      commercial endotoxin adsorbers for endotoxin removal in buffer solution, protein
      solution, serum and heparinized plasma; some of these were also characterized in
      whole blood. The tested LPS adsorbers were Toraymyxin(r) PMX-20R, Alteco(r) LPS
      Adsorber, DEAE-Sepharose, Polymyxin B-Agarose, and EndoTrap(r) red. METHODS: The
      adsorber materials were tested in buffer and protein solutions spiked with
      fluorescently labeled LPS (100 ng/ml). Additionally, batch tests with LPS-spiked
      serum, heparinized plasma and whole blood were performed with an LPS
      concentration of 5 ng/ml. Additionally, the washing solutions of the two tested
      Polymyxin B (PMB)-based adsorbers were analyzed for PMB release to determine if
      the resulting LPS inactivation was caused by PMB leakage. RESULTS: The results
      show that DEAE-Sepharose was most effective in LPS adsorption. Of the other
      tested endotoxin removal materials, only the PMB-based adsorbers were able to
      reduce the LPS activity. However, we were able to show that the reduction in LPS
      activity was caused by desorbed PMB, which inactivates endotoxins. CONCLUSIONS:
      None of the adsorbents that were tested in this study showed promising results
      for potential use in extracorporeal blood purification.

PMID- 24744166
TI  - The accuracy of a continuous volumetric balancing system in pediatric continuous
      renal replacement therapy.
AB  - BACKGROUND: In pediatric continuous renal replacement therapy (CRRT) patients,
      accurate ultrafiltration (UF) measurement is essential, as both over- and under
      UF may result in suboptimal outcomes. Traditionally, CRRT has relied on scale
      based UF measurements; however, the recent development of a continuous volumetric
      balancing system has allowed for the advent of scale-less CRRT. METHODS: To
      assess the accuracy of the volumetric balancing system, we designed a
      continuously measuring digital scale, which accounted for dialysate use and
      collected effluent, allowing us to independently measure UF volume and compare it
      with the machine reported UF volume. RESULTS: In four low weight (6.9-16.7 kg)
      pediatric CRRT patients, we measured the UF volume over 20 separate runs,
      comprising a total of 318 hours. Over this time, the total measured UF volume was
      50,550 mL +/- 296 mL, whereas the total reported UF volume was 50,733 mL, a
      difference of 183 mL +/- 296 mL (0.6 +/- 0.9 ml/h), or 0.4 +/- 0.6%. For each
      patient, over 48-112 hours per patient, the differences between the total
      measured and total reported UF volumes ranged from -7.8 +/- 1.7 ml/h to +9.7 +/-
      1.8 ml/h, or -6.0 +/- 1.3% to +5.4 +/- 1.0%. CONCLUSIONS: In low-weight,
      pediatric CRRT patients, the scale-less continuous volumetric balancing system
      delivers accurate ultrafiltration.

PMID- 24744168
TI  - Blood component usage during extracorporeal membrane oxygenation: experience in
      98 patients at a Latin-American tertiary hospital.
AB  - BACKGROUND/AIMS: Hemorrhagic complications during ECMO may affect a large
      proportion of the patients depending on the clinical setting. To guarantee
      optimal delivery of blood products to these patients, blood banks require updated
      information on the transfusion requirements. Few studies to date provide this
      information. This work assesses transfusion requirements in neonates and children
      during ECMO during the past 9 years. METHODS: We reviewed blood bank and hospital
      records of patients who underwent ECMO at our institution between May 2003 and
      May 2012. Data obtained included age, weight, diagnosis, type, length of ECMO,
      and daily transfusion requirements during ECMO. Descriptive and non-parametric
      inferential statistic analyses were performed. Our series included 98 patients.
      RESULTS: Mean time of patients on ECMO was 9.2 days, with the longest treatment
      spanning 22 days. Mean daily transfusion requirements were 39.5 ml/kg of RBC,
      12.9 ml/kg of plasma, 34.3 ml/kg of platelets and 1.4 ml/kg of cryoprecipitate.
      Patients who underwent ECMO due to cardiac disease or congenital diaphragmatic
      hernia (CDH) required significantly higher transfusion volumes of plasma
      (p<0.05), platelets (p< 0.05) and cryoprecipitate (p<0.05) when compared to
      patients underwent ECMO due to respiratory disease. Concomitant with the aging of
      ECMO circuits, patients showed increased requirements of RBC, plasma, and CRYO
      around the seventh day of the ECMO run. This effect was not observed for
      platelets, which remained nearly consistent around 2.2 transfusions/day.
      CONCLUSIONS: ECMO patients required significant transfusion support, which was
      particularly higher among patients who underwent ECMO due to cardiac disease or
      congenital diaphragmatic hernia.

PMID- 24744169
TI  - Numerical washout study of a pulsatile total artificial heart.
AB  - PURPOSE: For blood pumps with long term indication, blood stagnation can result
      in excessive thromboembolic risks for patients. This study numerically
      investigates the washout performance of the left pump chamber of a pulsatile
      total artificial heart (TAH) as well as the sensitivity of the rotational
      orientation of the inlet bileaflet mechanical heart valve (MHV) on blood
      stagnation. METHODS: To quantitatively evaluate the washout efficiency, a fluid
      structure interaction (FSI) simulation of the artificial heart pumping process
      was combined with a blood washout model. Four geometries with different
      orientations (0 degrees , 45 degrees , 90 degrees  and 135 degrees ) of the inlet
      valve were compared with respect to washout performance. RESULTS: The calculated
      flow field showed a high level of agreement with particle image velocimetry (PIV)
      measurements. Almost complete washout was achievable after three ejection phases.
      Remains of old blood in relation to the chamber volume was below 0.6% for all
      configurations and were mainly detected opposite to the inlet and outlet port at
      the square edge where the membrane and the pump chamber are connected. Only a
      small variation in the washout efficiency and the general flow field was
      observed. An orientation of 0 degrees  showed minor advantages with respect to
      blood stagnation and recirculation. CONCLUSIONS: Bileaflet MHVs were demonstrated
      to be only slightly sensitive to rotation regarding the washout performance of
      the TAH. The proposed numerical washout model proved to be an adequate tool to
      quantitatively compare different configurations and designs of the artificial
      organ regarding the potential for blood stagnation where experimental
      measurements are limited.

PMID- 24744170
TI  - A novel artificial anal sphincter system in an in vitro and in vivo experiment.
AB  - This paper presents some of the latest progress in the development of a novel
      artificial anal sphincter system (AASS) to treat severe fecal incontinence. We
      have redesigned and integrated an intelligent, remote-controlled artificial anal
      sphincter based on biological signal feedback mechanisms. The device consists of
      an external telemetry unit, an internal artificial anal sphincter (IAAS), and a
      transcutaneous energy transfer system (TETS). The mechanical medical micropump of
      the IAAS can realize bidirectional flow with a maximum flow rate of 8.5 ml/min
      and can build backpressure up to 170 kPa. The design of the prosthesis reduces
      occlusion pressure and allows for low inflation volumes (9 mL-10.5 mL); operating
      pressures between 4.05 kPa and 7.16 kPa indicate that the risk of ischemic injury
      to the bowel is minimal. Furthermore, the rechargeable battery based on TETS puts
      the operation time at an estimated 2 days. The performance characteristics of the
      AASS and its efficiency in achieving continence and sensing the stool inside the
      anorectum were evaluated in vitro and in vivo in a pig model. Experimental
      results confirm that the system can maintain continence and build the sense of
      defecation successfully. Moreover, this innovation can be integrated into not
      only severe fecal incontinence, erectile dysfunction, and therapy-resistant
      reflux disease, but also morbid adiposity therapeutic AASS applications. 

PMID- 24744171
TI  - Assessment of accuracy of robotically assisted unicompartmental arthroplasty.
AB  - PURPOSE: The purpose of this study was to analyse the accuracy of component
      placement during unicompartmental knee arthroplasty (UKA) using a robotic
      assisted system. METHODS: Two hundred and six patients (232 knees) who underwent
      medial robotic-assisted UKA were retrospectively studied. Femoral and tibial
      sagittal and coronal alignments were measured in the post-operative radiographs
      and were compared with the equivalent measurements collected during the intra
      operative period by the robotic system. Mismatch between pre-planning and post
      operative radiography was assessed against accuracy of the prosthesis insertion.
      RESULTS: Robotic-assisted surgery for medial UKA resulted in an average
      difference of 2.2 degrees  +/- 1.7 degrees  to 3.6 degrees  +/- 3.3 degrees 
      depending on the component and radiographic view between the intra-operatively
      planned and post-operative measurements. Mismatch between pre-planning and post
      operative radiography (inaccuracy) was related to improper cementing technique of
      the prosthesis in all measurements (except for tibial sagittal axis) rather than
      wrong bony cuts performed by the robotic arm. CONCLUSION: Robotic-assisted medial
      UKA results in accurate prosthesis position. Inaccuracy may be attributed to
      suboptimal cementing technique.

PMID- 24744173
TI  - Bilateral medial patellofemoral ligament reconstruction in high-level athletes.
AB  - This report presents two cases of high-level athletes with bilateral patellar
      dislocations who were able to return to their preinjury level of activity after
      bilateral medial patellofemoral ligament (MPFL) reconstruction, without any major
      complications. Patient 1 was a 19-year-old male volleyball player for a top-level
      college volleyball team, and patient 2 was a 24-year-old woman who was a member
      of a national-level adult softball team. MPFL reconstruction could be an
      effective treatment for bilateral patellar dislocation in high-level athletes.
      Level of evidence V. 

PMID- 24744172
TI  - Biomechanical evaluation of suture-tendon interface and tissue holding of three
      suture configurations in torn and degenerated versus intact human rotator cuffs.
AB  - PURPOSE: The purpose of this study was to biomechanically evaluate suture-tendon
      interface and tissue holding of three sutures in torn and degenerated versus
      intact human rotator cuffs. METHODS: Sixty-three human rotator cuff tendons were
      divided into torn degenerated group (TDG), n = 21 and intact group (IG), n = 42.
      Ultimate tension load (UTL) and cyclic loading were tested for three arthroscopic
      sutures: simple, horizontal, and massive cuff sutures (MCS). RESULTS: Ultimate
      tension load was significantly higher (p < 0.05) for the MCS (194 +/- 68 N) in
      comparison with the simple (105 +/- 48 N) and horizontal sutures (141 +/- 49 N)
      in IG. In TDG, UTL was not significantly higher (n.s.) for MCS (118 +/- 49 N),
      simple (79 +/- 30 N), and horizontal sutures (107 +/- 28 N) in comparison with
      IG. MCS (118 +/- 49 N) showed no significantly superior UTL in comparison with
      the simple and horizontal sutures in the TDG. MCA elongation was 0.6 +/- 0.7 mm
      in the IG and 1.3 +/- 0.7 mm in the TDG, while horizontal suture elongation was
      0.7 +/- 0.4 mm in the IG and 1.3 +/- 0.5 mm in the TDG. Simple suture elongation
      was 1.1 +/- 0.5 mm in the IG and 1.6 +/- 0.7 mm in the TDG. CONCLUSION: Human
      torn and degenerated rotator cuffs have poor tissue quality, significantly lower
      UTL and higher cyclic elongation in comparison with intact cuffs regardless of
      the type of suture used for repair, which invites the need for repair techniques
      that grasps greater tissue volume in addition to augmentation techniques.
      CLINICAL RELEVANCE: Clinicians better use repair techniques that grasp greater
      tissue volume (e.g. MCS, modified Mason-Allen cross bridge, double-row cross
      bridge, etc.) when repairing the torn and degenerated rotator cuffs.

PMID- 24744174
TI  - The origin points of the knee collateral ligaments: an MRI study on paediatric
      patients during growth.
AB  - PURPOSE: Different femoral origins for both the medial collateral ligament (MCL)
      and the lateral collateral ligament (LCL) have been reported in the growing
      skeleton (epiphyseal and metaphyseal). Knowledge about the exact attachment sites
      is mandatory for anatomically correct reconstruction. This study assesses the
      femoral origins of the knee collateral ligaments in skeletally immature
      individuals using magnetic resonance imaging (MRI). METHODS: MRIs of 336 knee
      joints (median age 15 years (range 2-18 years), m = 209 and f = 127) were
      retrospectively analysed to assess the distances between the femoral origins of
      the MCL and LCL to the distal femoral growth plate. In 175 patients, the body
      sizes were additionally retrieved from medical records. RESULTS: Both MCL and LCL
      ligament origins were invariably located on the epiphysis. Mean MCL origin-growth
      plate distance was 9.6 mm (SD 2.1 mm; range 2.2-13.6 mm) in boys and 8.6 mm (SD
      1.5 mm; range 3.4-12.0 mm) in girls. Mean LCL origin-growth plate distance was
      9.3 mm (SD 1.8 mm; range 4.3-13.0 mm) in boys and 8.2 mm (SD 1.5 mm; range 3.4
      11.8 mm) in girls. The distance between the growth plate and both collateral
      ligaments as well as the length of the LCL correlated positively with patients'
      age and body size (MCL R(2) = 0.673 and 0.556, LCL R (2) = 0.734 and 0.645, LCL
      length R(2) = 0.589 and 0.741; all p < 0.001). CONCLUSIONS: During growth, the
      femoral origins of the MCL and the LCL are constantly located on the distal
      femoral epiphysis. There is a linear increase in the distances from the
      ligaments' origins to the growth plate according to age and body size. This new
      information may be of clinical importance for reconstructive surgery of the
      knee's collateral ligaments.

PMID- 24744175
TI  - Varus knee osteoarthritis: how can we identify ACL insufficiency?
AB  - PURPOSE: The aim of this prospective study was to determine the clinical value of
      lateral radiographs and corresponding MRI scans in the preoperative evaluation of
      the functional integrity of the anterior cruciate ligament (ACL) in a consecutive
      series of 78 patients (93 knees) with medial compartment osteoarthritis. METHODS:
      All knees received standardised radiographs and MRI imagery. The wear pattern on
      the lateral radiograph was described based on a modified Keyes classification. On
      MRI, the ACL and the percentage of intact posterior cartilage in relation to the
      anteroposterior tibia width were assessed. RESULTS: The MRI showed an intact ACL
      in 23 (25 %) knees, evidence of ACL degeneration in 54 (58 %) knees and a
      complete ACL tear in 16 (17 %) knees. All knees with an intact ACL showed >=14 %
      intact posterior cartilage on sagittal MRI scans, except for one knee. All knees
      with a torn ACL demonstrated <14 % intact posterior cartilage. Of the 54 knees
      with evidence of ACL degeneration, eight knees had <14 % intact posterior
      cartilage similar to the wear pattern present in knees with torn ACLs. Out of the
      24 knees with a torn or degenerated ACL and <14 % intact posterior cartilage on
      MRI, 23 (96 %) knees demonstrated posterior bony erosion on corresponding lateral
      radiographs. CONCLUSIONS: The assessment of intact posterior tibial cartilage on
      MRI and lateral radiographs helps to identify knees with functional ACL
      insufficiency. MRI with assessment of both the ACL morphology and the underlying
      tibial wear pattern appears to provide additional clinical benefit in cases in
      which the extent of posterior bony erosion on the lateral radiograph cannot be
      assessed with confidence. LEVEL OF EVIDENCE: Diagnostic study, Level II.

PMID- 24744176
TI  - Bao-yu: a mental disorder or a cultural icon?
AB  - The embodied human subject is dynamically connected to his or her historico
      sociocultural context, the soil from which a person's psyche is nourished as
      multiplex meanings are absorbed and enable personal development. In each culture
      certain towering artistic works embody this perspective. The Dream of the Red
      Chamber introduces Jia Bao-yu--a scion of the prestigious Jia family--and his
      relationships with a large cast of characters. Bao-yu is controversial but, at
      the time of the family's tragic collapse, he can be seen as embodying a spiritual
      struggle in which his instinct, nature, sensitivity, and creativity are grounded
      in his transcendent relationship with a fragment of the world stone, an eternal
      source of energy and creativity. We are invited to draw on a metaphysical level
      of thought to consider his struggles with man-made hierarchies and a situated
      historico-sociocultural order in such a way as to live out his spiritual being.
      As such, the novel is closely relevant to questions of spirituality in bioethics.
      Through personal experiences, passions, creativity, and relationships with
      others, the body is inscribed, forming the soul, which may be misconstrued (for
      instance, through a medical or Cartesian reformulation of events) but which can
      be seen as the site of ethical and spiritual thought.

PMID- 24744177
TI  - Amoralist rationalism? A response to Joel Marks: commentary on "Animal
      abolitionism meets moral abolitionism: cutting the Gordian knot of applied
      ethics" by Joel Marks.
AB  - In a recent article, Joel Marks presents the amoralist argument against
      vivisection, or animal laboratory experimentation. He argues that ethical
      theories that seek to uncover some universal morality are in fact useless and
      unnecessary for ethical deliberations meant to determine what constitutes an
      appropriate action in a specific circumstance. I agree with Marks' conclusion. I
      too believe that vivisection is indefensible, both from a scientific and
      philosophical perspective. I also believe that we should become vegan
      (unfortunately, like the two philosophers mentioned by Marks, I too am still
      struggling to reduce my meat and dairy consumption). However, I am in the dark as
      to Marks' vision of normative deliberations in the spirit of amoralism and
      desirism. 

PMID- 24744178
TI  - Reproductive tissue and contract.

PMID- 24744179
TI  - Analysis of the Hyalinization Reaction in Otosclerosis.
AB  - IMPORTANCE: Otosclerotic bone has been observed to penetrate the endosteal layer
      of the cochlea, resulting in direct contact with the soft-tissue structures of
      the inner ear. Sensorineural hearing loss has been observed in some, but not all,
      of these cases. The development of histologic changes occurring in the cochlear
      soft tissues at the site of otosclerotic endosteal penetration has been
      descriptively referred to as a hyalinization reaction. The role of the
      hyalinization reaction in the development of hearing loss is unknown. OBJECTIVE:
      To evaluate the composition of these hyalinized soft tissues using immunostaining
      techniques. DESIGN, SETTING, AND PARTICIPANTS: Retrospective review in a human
      temporal bone histopathology research laboratory of 3 specimens from patients
      with endosteal otosclerotic involvement. INTERVENTIONS: Evaluation of human
      temporal bone pathology findings. MAIN OUTCOMES AND MEASURES: Human temporal bone
      sections with endosteal otosclerotic involvement were studied using
      immunostaining techniques to identify collagen I, chondroitin sulfate, and
      keratan sulfate deposition in the hyalinization reaction tissue. RESULTS: Intense
      collagen I staining was demonstrated within the hyalinization reaction in an
      onionskin-like layered fashion. In addition, dual immunofluorescence-stained
      sections for proteoglycans revealed both chondroitin sulfate and keratan sulfate
      deposition in the hyalinized tissue. CONCLUSIONS AND RELEVANCE: The tissue of the
      hyalinization reaction appears to be composed of collagen I, chondroitin sulfate,
      and keratan sulfate, which are known to act as molecular barriers. This
      observation suggests that the hyalinization reaction may limit the diffusion of
      toxic substances produced by otosclerotic bone into the soft tissues and fluids
      of the cochlea.

PMID- 24744180
TI  - Second harmonic generation imaging distinguishes both high-grade dysplasia and
      cancer from normal colonic mucosa.
AB  - BACKGROUND AND AIM: Second harmonic generation (SHG) is a novel imaging
      technology that could provide optical biopsy during endoscopy with advantages
      over current technology. SHG has the unique ability to evaluate the amount of
      extracellular matrix collagen protein and its alignment. METHODS: Hematoxylin-
      and eosin-stained slides from colon biopsies (normal, low-grade dysplasia (LGD),
      high-grade dysplasia (HGD), and cancer) were examined with SHG imaging. Both
      signal intensity and collagen fiber alignment were measured. Average intensity
      per pixel (AIPP) was obtained, and an analyzing polarizer was used to calculate
      beta, an alignment parameter. RESULTS: The mean AIPP for normal mucosa was 48,
      LGD was 38, HGD was 42, and malignancy was 123 (p < 0.01). The AIPP ROC curve
      between malignant versus non-malignant tissue was 0.96 (0.93-0.99). An AIPP value
      of 60 can differentiate malignancy with 87 % sensitivity and 90 % specificity.
      The mean beta for normal tissue was 0.490, LGD was 0.379, HGD was 0.345, and
      cancer was 0.453 (p = 0.013), with a normal tissue mean rank of 6.5 compared to
      2.5 for HGD (p = 0.029). CONCLUSIONS: SHG signal intensity can differentiate
      malignant from non-malignant colonic polyp tissue with high sensitivity and
      specificity. Anisotropic polarization can discern HGD from normal colonic polyp
      tissue. SHG can thus distinguish both HGD and malignant lesions in an objective
      numeric fashion, without contrast agents or interpretation skills. SHG could be
      incorporated into endoscopy equipment to enhance white light endoscopy.

PMID- 24744182
TI  - A reversed-reward contingency task reveals causal knowledge in chimpanzees (Pan
      troglodytes).
AB  - In the reversed-reward contingency task, subjects are required to choose the less
      preferred of two options in order to obtain the more preferred one. Usually, this
      task is used to measure inhibitory skills, but it could also be used to measure
      how strong the subjects' preferences are. We presented chimpanzees with support
      tasks where only one of two paper strips could physically bring food into reach.
      Subjects were rewarded for choosing the non-functional strip. In Experiment 1,
      subjects failed to pick the non-baited strip. In Experiment 2, subjects failed to
      pick the broken strip. Chimpanzees performed worse in these tasks than in other
      similar tasks where instead of paper strips, there were similar shapes painted on
      a platform. The fact that subjects found the reversed-reward contingency task
      based on causality more difficult to solve than a perceptually similar task with
      no causality involved (i.e., arbitrary) suggests that they did not treat real
      strips as an arbitrary task. Instead, they must have had some causal knowledge of
      the support problem that made them prefer functional over non-functional strips
      despite the contrary reward regime. 

PMID- 24744181
TI  - Seroprevalence of hepatitis E virus (HEV) in humans living in high pig density
      areas of Germany.
AB  - An increase in acute autochthonous hepatitis E virus (HEV) infections has been
      recorded in Germany. These are suspected to be zoonotically transmitted from wild
      boar, deer and domestic pig. The latter may represent a major reservoir for HEV.
      In this study, 537 sera from humans living in Westphalia and Lower Saxony,
      representing areas of high pig density in Germany, were tested for the presence
      of HEV-specific antibodies. Among them were 302 individuals with occupational,
      direct contact to pigs and 235 individuals without direct contact to pigs. Two
      commercial tests and one in-house assay were applied for the detection of HEV
      specific immunoglobulin G (IgG) antibodies. Sera were also tested in an assay
      that detects all classes of HEV-specific antibodies. Depending on the test used,
      the seroprevalence ranged from 4.1 to 27.9 %. Exposition to pigs was found to be
      associated with a significantly higher seroprevalence in subjects with contact to
      pigs (13.2-32.8 %) compared with that in non-exposed humans (7.7-21.7 %). In
      particular, individuals younger than 40 years with occupational exposure
      exhibited a markedly higher HEV seroprevalence compared with non-exposed
      individuals of that age group. In general, HEV seroprevalence increased with age
      resulting in a similar prevalence level in the age group of >= 50 years for
      exposed and non-exposed individuals. Analysis of all sera by a commercial anti
      HEV IgM ELISA revealed 35 positive and 25 borderline samples. However, only one
      positive serum could be confirmed by an IgM line assay. Selected samples from IgM
      and/or IgG as well as total HEV antibody-positive individuals were also tested
      for the presence of HEV RNA. In one of the 78 samples, the only IgM ELISA
      positive and IgM line assay confirmed sample, RNA of HEV genotype 3 was detected.
      This sequence has high similarity to HEV sequences obtained from wild boars and
      domestic pigs from Germany and The Netherlands. This study demonstrates that in
      addition to the consumption of raw or undercooked meat, direct contact to pigs
      has to be considered as an additional risk factor for HEV infection.

PMID- 24744183
TI  - An EP4 antagonist ONO-AE3-208 suppresses cell invasion, migration, and metastasis
      of prostate cancer.
AB  - EP4 is one of the prostaglandin E2 receptors, which is the most common prostanoid
      and is associated with inflammatory disease and cancer. We previously reported
      that over-expression of EP4 was one of the mechanisms responsible for progression
      to castration-resistant prostate cancer, and an EP4 antagonist ONO-AE3-208 in
      vivo suppressed the castration-resistant progression regulating the activation of
      androgen receptor. The aim of this study was to analyze the association of EP4
      with prostate cancer metastasis and the efficacy of ONO-AE3-208 for suppressing
      the metastasis. The expression levels of EP4 mRNA were evaluated in prostate
      cancer cell lines, LNCaP, and PC3. EP4 over-expressing LNCaP was established, and
      their cell invasiveness was compared with the control LNCaP (LNCaP/mock). The in
      vitro cell proliferation, invasion, and migration of these cells were examined
      under different concentrations of ONO-AE3-208. An in vivo bone metastatic mouse
      model was constructed by inoculating luciferase expressing PC3 cells into left
      ventricle of nude mice. Their bone metastasis was observed by bioluminescent
      imaging with or without ONO-AE3-208 administration. The EP4 mRNA expression
      levels were higher in PC3 than in LNCaP, and EP4 over-expression of LNCaP cells
      enhanced their cell invasiveness. The in vitro cell invasion and migration were
      suppressed by ONO-AE3-208 in a dose-dependent manner without affecting cell
      proliferation. The in vivo bone metastasis of PC3 was also suppressed by ONO-AE3
      208 treatment. EP4 expression levels were correlated with prostate cancer cell
      invasiveness and EP4 specific antagonist ONO-AE3-208 suppressed cell invasion,
      migration, and bone metastasis, indicating that it is a potential novel
      therapeutic modality for the treatment of metastatic prostate cancer.

PMID- 24744184
TI  - [Testicular cancer - a matter of geography? Epidemiology and etiopathogenesis of
      germ cell tumors].
AB  - More than 90 % of testicular tumors are germ cell tumors. There is no doubt that
      ethnicity is one of the single overriding etiological factors in the development
      of these tumors. White males living in western industrialized countries,
      particularly in northern Europe show the highest incidence rates, whereas black
      males in Africa show the lowest. These differences are the result of interaction
      of genetic factors and exogenous noxious agents. Some of these agents are
      chemical substances with an estrogen-like effect. Many exogenous substances have
      been blamed for causing testicular cancer, but clear epidemiological evidence is
      lacking for most cases. Some well-established risk factors prevail, such as
      cryptorchidism, familial association, gonadal dysgenesis (intersex) and germ cell
      tumor in the contralateral testis. In terms of importance, overalimentation
      appears to outweigh occupation. The development of germ cell tumors is assumed to
      have an intrauterine origin through defect gonocytes which evolve into atypical
      germ cells of unclassified intratubular germ cell neoplasms. The trigger event
      is, however, the appearance of isochromosome 12p, which makes these cells
      aggressive and results in overt invasive testicular cancer. 

PMID- 24744185
TI  - [Testicular seminomas. The classical and the less classical ones].
AB  - Testicular germ cell tumors are generally rare but represent the most common
      solid neoplasms in young men. They are subdivided into seminomas and non
      seminomatous germ cell tumors. Usually the diagnosis of a seminoma is
      straightforward due to the characteristic morphology, although problems in
      differential diagnosis can occur because of unusual histological growth patterns.
      This article describes the challenging differential diagnosis with respect to
      seminomas versus non-seminomatous germ cell tumors, sex cord stromal tumors,
      lymphomas and non-neoplastic conditions, such as scars and inflammatory changes.
      In addition, prognostic factors for seminomas are presented and discussed. 

PMID- 24744186
TI  - Biofilm formation and persistence on abiotic surfaces in the context of food and
      medical environments.
AB  - The biofilm formation on abiotic surfaces in food and medical sectors constitutes
      a great public health concerns. In fact, biofilms present a persistent source for
      pathogens, such as Pseudomonas aeruginosa and Staphylococcus aureus, which lead
      to severe infections such as foodborne and nosocomial infections. Such biofilms
      are also a source of material deterioration and failure. The environmental
      conditions, commonly met in food and medical area, seem also to enhance the
      biofilm formation and their resistance to disinfectant agents. In this regard,
      this review highlights the effect of environmental conditions on bacterial
      adhesion and biofilm formation on abiotic surfaces in the context of food and
      medical environment. It also describes the current and emergent strategies used
      to study the biofilm formation and its eradication. The mechanisms of biofilm
      resistance to commercialized disinfectants are also discussed, since this
      phenomenon remains unclear to date. 

PMID- 24744187
TI  - Fluoride concentrations in the pineal gland, brain and bone of goosander (Mergus
      merganser) and its prey in Odra River estuary in Poland.
AB  - The aim of the study was to investigate fluoride concentrations in bone, brain
      and pineal gland of goosander Mergus merganser wintering in the Odra estuary
      (Poland) as well as in fish originating from its digestive tract. The fluoride
      concentrations were determined with potentiometric method. Medians of
      concentrations in goosander had the highest and the lowest values in pineal gland
      and brain (>760 and <190 mg/kg, respectively). Fluoride concentration in the
      pineal gland was significantly greater than in the bone and the brain of the
      duck. In fish, the fluoride concentration ranged from 37 to 640 mg/kg and
      significant correlation was revealed between the fluoride concentration and fish
      weight and length. Based on own results and data of other authors, a daily
      fluoride intake by the goosander in the Odra estuary was estimated at 15 mg. So
      high fluoride concentrations like in the duck have not been found in mammal
      brains. 

PMID- 24744188
TI  - Gastric bypass with long alimentary limb or long pancreato-biliary limb--long
      term results on weight loss, resolution of co-morbidities and metabolic
      parameters.
AB  - BACKGROUND: Several studies indicate that increasing the alimentary limb length
      in gastric bypass surgery produces only a minor improvement of excess BMI loss.
      Few studies have addressed the efficacy of increasing the length of the
      pancreatico-biliary limb. METHODS: Here, we present a prospective randomized
      study of 187 consecutive laparoscopic Roux-Y gastric bypass operations operated
      over 2 years (2004-2005) in Iceland. The patients were operated with a gastric
      bypass with either a 2-m biliopancreatic (BP)-limb and a 60-cm alimentary (A)
      limb (n = 93) or with a 150-cm A-limb and a 60-cm BP-limb (n = 94). RESULTS:
      Preoperative median BMI was 44.1 (38-70), median age 35.5 (17-74) years, and 85 %
      of the patients were female. Follow-up rate after 5 years was 85 %. Eighteen
      months following surgery, the weight loss was significantly higher in the BP-limb
      group (p < 0.001), and this difference remained 7 years after surgery. Weight
      regain occurred in both groups, and 7 years after surgery, excess BMI loss
      (EBMIL) was 78.4 % in the BP-limb group compared to 67.1 % in the A-limb group (p
      < 0.001). Most patients (78 %) needed supplementation adjustment (iron, vitamin D
      and calcium) during the study period, significantly more often in the BP-limb
      group compared to the A-limb group (p < 0.001). Patients in the BP-limb group had
      more frequent stools than patients in the A-limb group; otherwise, gastro
      intestinal symptoms rating scoring were comparable. Complication rate was
      similar. CONCLUSIONS: Gastric bypass with a 2-m BP-limb gives better weight loss
      than gastric bypass with a 60-cm BP-limb and a 150-cm A-limb. Metabolic follow-up
      is of utmost importance, as most patients needed repeated adjustments of their
      supplementation.

PMID- 24744189
TI  - Measurement of disordered eating following bariatric surgery: a systematic review
      of the literature.
AB  - Disordered eating is elevated in bariatric surgery patients and is a risk factor
      for poor surgical outcomes. A systematic review evaluated the definitions and
      measurement methods used to identify and assess disordered eating in patients
      following bariatric surgery. One hundred articles were identified featuring 35
      questionnaires and 23 interviews. There were numerous variations to diagnostic
      criteria and amendments to measures to account for the post-surgical eating
      context. Only 20% of questionnaires and 4% of interviews had reported
      psychometric evaluation in post-surgery samples. Results highlight the need for a
      consistent definition of disordered eating and for current assessment measures to
      be (a) adapted to account for the altered gastrointestinal system in patients
      following surgery and (b) psychometrically evaluated in bariatric surgery
      patients.

PMID- 24744190
TI  - Berberine mitigates cyclophosphamide-induced hepatotoxicity by modulating
      antioxidant status and inflammatory cytokines.
AB  - OBJECTIVES: The present study was designed to investigate the possible protective
      effects of berberine against cyclophosphamide (CP)-induced hepatotoxicity in
      rats. METHODS: The experimental rats were treated with berberine orally at a dose
      of 50 mg/kg for 11 consecutive days after the administration of a single
      intraperitoneal dose of CP (200 mg/kg). The hepatoprotective effect of berberine
      was evaluated by assaying liver function markers, the pro-inflammatory cytokine
      tumor necrosis factor alpha (TNF-alpha), antioxidant defense system and gene
      expressions of both TNF-alpha and cyclooxygenase 2 (COX-2). RESULTS: The
      biochemical results showed that administration of CP induced hepatic damage
      associated with a significant increase in the serum marker enzymes aspartate and
      alanine transaminases (AST, ALT) and alkaline phosphatase (ALP), and a
      significant increase in serum total bilirubin accompanied with a decrease in
      serum albumin concentration. In addition, CP-administration induced oxidative
      stress in the liver as evident from the increased lipid peroxidation (LPO),
      declined glutathione (GSH) content and glutathione peroxidase (GPx) and
      superoxide dismutase (SOD) activities. Moreover, administration of CP was
      associated with a significant increase in serum TNF-alpha. Similarly, CP
      administration was accompanied by a significant increase in the mRNA expression
      of both TNF-alpha and COX-2 in the liver as indicated by the qPCR assay.
      Concomitant administration of berberine efficiently alleviated the altered
      biochemical parameters. CONCLUSION: Berberine showed a marked hepatoprotective
      effect against CP-induced hepatotoxicity through alleviation of the elevated
      serum marker enzymes in addition to its antioxidant and anti-inflammatory
      efficacies.

PMID- 24744191
TI  - Biochemical and clinical outcomes after high-dose salvage radiotherapy as
      monotherapy for prostate cancer.
AB  - PURPOSE: To retrospectively evaluate the role of high-dose salvage radiotherapy
      (SRT) alone with regard to biochemical and clinical outcomes in patients with
      biochemical failure (BF) after radical prostatectomy (RP). METHODS: Between
      January 2003 and August 2011, 168 hormone-naive localized prostate cancer
      patients received SRT alone for post-RP BF in a single institution and were
      retrospectively analyzed. Multivariate analysis was performed to determine the
      independent prognostic impact of clinical factors on biochemical and clinical
      outcomes [biochemical relapse-free survival (bRFS), clinical relapse-free
      survival (cRFS), cancer-specific survival (CSS) and overall survival (OS)].
      RESULTS: Median follow-up was 54 months. Actuarial bRFS, cRFS, CSS and OS at 5
      years were, respectively, 64, 86.2, 94.5 and 96.3 %. On multivariate analysis,
      nadir PSA (nPSA) after SRT was significantly associated with bRFS (HR 15, p =
      0.001) and cRFS (HR 9, p = 0.001), while CSS was associated with RT dose (>=70
      Gy; HR 1.9 p = 0.023), pre-RT PSA (<1.5 vs. >=1.5 ng/mL; HR 1.3, p = 0.008) and
      age (>75 years; HR 1.2, p = 0.05). OS was significantly correlated with pre-SRT
      PSA (linear correlation; HR 1.1, p = 0.023) and age (<75 vs. >= 75 years; HR 1.1,
      p = 0.026). CONCLUSIONS: Effective biochemical and clinical control rates may be
      safely achieved administering SRT with high doses (>=72 Gy) and using conformal
      techniques, especially in older patients presenting with lower pre-SRT PSA
      values. A lower nPSA after SRT predicts for better 5 years bRFS and cRFS rates.

PMID- 24744192
TI  - Genetics in PBC: what do the "risk genes" teach us?
AB  - Primary biliary cirrhosis is characterised by a progressive and destructive
      lymphocytic cholangitis, targeting small intra-hepatic bile ducts. In association
      with the histologic liver injury, patients characteristically express highly
      specific auto-antibodies that recognise a conserved epitope of the pyruvate
      dehydrogenase complex found on the inner membrane of the mitochondria. Family
      studies demonstrate a clear increased incidence and prevalence of associated
      autoimmune diseases; and historically, a clear HLA association with disease has
      been evident. With the use of a high-throughput whole-genome array technology,
      significant insights into the non-HLA loci associated with risk for disease
      development have been made. These studies, which have primarily incorporated
      genome-wide association screens and targeted analysis of immune genes, have
      highlighted the integral roles for immune cell development and function in
      disease risk. This has revealed the IL-12/JAK-STAT signalling pathway as a key
      etiologic factor. In conjunction with a better understanding of environmental
      triggers, such work lays the foundation for better disease insights
      mechanistically and, hopefully, therapeutically. Obstacles to uncovering all the
      associated genetic risk and the correlation between genotype and phenotype remain
      to be circumvented, as do better appreciation of the processes that underpin not
      only disease initiation but also presentation and outcome. 

PMID- 24744193
TI  - Clinical characteristics, pathological features and surgical outcomes of focal
      cortical dysplasia (FCD) type II: correlation with pathological subtypes.
AB  - Focal cortical dysplasia (FCD) type II is a major cause of drug-resistant
      epilepsy. In order to gain insight into the possible correlations between FCD II
      pathological pattern and different clinical characteristics (including clinical
      information, imaging characteristics and surgical outcomes), different
      clinicopathological characteristics in two types of FCD II were analyzed
      (especially in FCD IIb). The mean age of seizure onset and disease duration of 78
      patients was 11.0 and 11.2 years, respectively. Patients with FCD type IIb had
      earlier seizure onset compared with those with FCD type IIa. Pathological subtype
      IIb was predominantly in frontal lobe and subtype IIa was predominantly seen in
      temporal. Type IIb demonstrated significantly more signal abnormalities in fluid
      attenuated inversion recovery (FLAIR) images and T2 images than Type IIa. The
      rate of satisfactory seizure outcome was 67.64 % in the FCD IIa group, while
      relative higher, 88.63 %, in the FCD IIb group. All these characteristics may
      assist in their earlier diagnosis and improve the predictability of surgical
      management.

PMID- 24744194
TI  - Factors associated with early hospital arrival in acute ischemic stroke patients.
AB  - Early diagnosis and treatment in acute ischemic stroke are crucial in terms of
      survival and disability. Many stroke patients remain disabled because of the
      treatment delay. The purpose of this study was to investigate the factors
      associated with the early hospital arrival in acute ischemic stroke patients. 113
      patients diagnosed with acute ischemic stroke were included in this prospective
      study performed at the Karadeniz Technical University Medical Faculty Hospital.
      Patients' characteristics and patients' and relatives' emotional and behavioral
      reactions were compared between early (within 3 h) and late (after 3 h) arrival
      groups. 72.6 % of patients arrived at hospital within 3 h from symptoms onset.
      Univariate analysis revealed that history of atrial fibrillation (p = 0.04) and
      coronary heart disease (p = 0.02), sudden onset of symptoms (p = 0.001), loss of
      consciousness (p = 0.03), recognizing symptoms as stroke (p = 0.01), seeking
      immediate medical attention (p < 0.001), feelings of fear and panic (p = 0.001),
      arriving at hospital by ambulance having called the emergency medical services (p
      = 0.04) and National Institute of Health Stroke Scale (NIHSS) score (p = 0.001)
      were associated with hospital arrival within 3 h. A multivariate regression model
      demonstrated that recognizing symptoms as stroke (OR, 3.4; 95 % CI, 1.2-9.3) and
      atrial fibrillation (OR, 4.3; 95 % CI, 1.1-15.7) were independent factors
      associated with early arrival. The role in early arrival at hospital of
      recognizing symptoms as stroke and seeking immediate medical attention with
      transportation by ambulance emphasize the importance of public awareness
      concerning recognizing the symptoms of stroke and accessing emergency medical
      assistance.

PMID- 24744196
TI  - Underestimation rate of lobular intraepithelial neoplasia in vacuum-assisted
      breast biopsy.
AB  - OBJECTIVES: To evaluate the underestimation rate and clinical relevance of
      lobular neoplasia in vacuum-assisted breast biopsy (VABB). METHODS: A total of
      161 cases of LN were retrieved from 6,435 VABB. The histological diagnosis was
      ALH (atypical lobular hyperplasia) in 80 patients, LCIS (lobular carcinoma in
      situ) in 69 patients and PLCIS (pleomorphic lobular carcinoma in situ) in 12
      patients. Seventy-six patients were operated on within 2 years after VABB and 85
      were clinically and radiologically monitored. The mean follow-up was 5.2 years,
      and the prevalence of malignancy was evaluated in the group of 85 patients.
      RESULTS: The clinico-pathological characteristics significantly favouring surgery
      were larger lesions, occurrence of a residual lesion following VABB and
      histological LCIS and PLCIS subtypes. The VABB underestimation rate as compared
      to surgery was 7.1% for ALH, 12% for LCIS and 50% for PLCIS. Overall, 11 of the
      148 patients included in this survival analysis developed an ipsilateral tumour.
      CONCLUSION: Although obtained retrospectively in a relatively small series of
      patients, our data suggest that only patients with a diagnosis of PLCIS in VABB
      should be treated with surgery, whereas patients with ALH and LCIS could be
      monitored by clinical and radiological examinations. KEY POINTS: * The treatment
      of ALH and LCIS in VABB is still debated * Some authors favour radical treatment
      and others a more conservative approach * Only patients with PLCIS in VABB should
      be treated by surgery.

PMID- 24744195
TI  - Hypoxia and inflammation in children with sickle cell disease: implications for
      hippocampal functioning and episodic memory.
AB  - Children with sickle cell disease (SCD) suffer from systemic processes (e.g.,
      chronic anemia, recurrent hypoxic-ischemic events, chronic inflammation) that
      have been associated with neurocognitive impairment in a range of clinical
      populations, but which have been largely understudied in relation to specific
      domains of cognitive functioning in children with SCD. This review focuses on
      episodic memory, as the hippocampus may be especially vulnerable to the systemic
      processes associated with SCD. The first part of the paper outlines the
      pathophysiology of SCD and briefly reviews the extant literature on academic and
      cognitive functioning in children with SCD, emphasizing the dearth of research on
      episodic memory. Next, the complex systemic processes of hypoxia and inflammation
      associated with SCD are reviewed, along with research that has associated these
      processes with hippocampal damage and memory impairment. The paper concludes with
      suggestions for future research that are informed, in part, by the literature on
      developmental amnesia. 

PMID- 24744197
TI  - Prostate cancer: performance characteristics of combined T2W and DW-MRI scoring
      in the setting of template transperineal re-biopsy using MR-TRUS fusion.
AB  - OBJECTIVES: To measure the performance characteristics of combined T2-weighted
      (T2W) and diffusion-weighted (DW) magnetic resonance imaging (MRI) suspicion
      scoring prior to MR-transrectal ultrasound (TRUS) fusion template transperineal
      (TTP) re-biopsy. METHODS: Thirty-nine patients referred for prostate re-biopsy,
      with prior MRI examinations, were retrospectively included. The MR images,
      including T2W and DW-MRI, had been independently evaluated prospectively by two
      radiologists using a structured scoring system. An MR-TRUS fusion TTP re-biopsy
      was used for MR target and non-targeted biopsy cores. Targeting performance and
      correlation with disease status were evaluated on a per-patient and per-region
      basis. RESULTS: The cancer yield was 41% (16/39 patients). MR targeting
      accurately detected the disease in 12/16 (75%) cancerous patients and missed the
      disease in 4/16 (25%) patients, all with Gleason 3 + 3 disease. There was a
      significant relationship (P < 0.01) between MR suspicion score and the
      significance of cancer. Reader 1 had significantly higher sensitivity in the
      transition zone (TZ; 0.84) compared with the peripheral zone (PZ; 0.32) (P =
      0.04). Inter-reader agreement was moderate for the PZ and substantial for the TZ.
      CONCLUSIONS: MRI targeting is beneficial in the setting of TTP MR-TRUS fusion re
      biopsy and MR suspicion score relates to prostate cancer clinical significance. A
      T2W and DW-MRI structured scoring system results in good inter-reader agreement
      in this setting. KEY POINTS: * Pre-biopsy MRI aids the detection of high
      significance cancer during prostate re-biopsy. * MRI suspicion level correlates
      with the clinical significance of prostate cancer detected. * T2W and DW-MRI
      structured scoring of pre-biopsy MRI permits good inter-reader agreement.

PMID- 24744198
TI  - Perfusion and diffusion characteristics of cervical cancer based on intraxovel
      incoherent motion MR imaging-a pilot study.
AB  - OBJECTIVES: To investigate the tissue characteristics of cervical cancer based on
      the intravoxel incoherent motion (IVIM) model and to assess the IVIM parameters
      in tissue differentiation in the female pelvis. METHODS: Sixteen treatment-naive
      cervical cancer and 17 age-matched healthy subjects were prospectively recruited
      for diffusion-weighted (b = 0-1,000 s/mm(2)) and standard pelvic MRI. Bi
      exponential analysis was performed to derive the perfusion parameters f
      (perfusion fraction) and D* (pseudodiffusion coefficient) as well as the
      diffusion parameter D (true molecular diffusion coefficient) in cervical cancer
      (n = 16), normal cervix (n = 17), myometrium (n = 33) and leiomyoma (n = 14).
      Apparent diffusion coefficient (ADC) was calculated. Kruskal-Wallis test and
      receiver operating characteristics (ROC) curves were used. RESULTS: Cervical
      cancer had the lowest f (14.9 +/- 2.6%) and was significantly different from
      normal cervix and leiomyoma (p < 0.05). The D (0.86 +/- 0.16 x 10(-3) mm2/s) was
      lowest in cervical cancer and was significantly different from normal cervix and
      myometrium (p < 0.05) but not leiomyoma. No difference was observed in D*. D was
      consistently lower than ADC in all tissues. ROC curves indicated that f < 16.38%,
      D < 1.04 * 10(-3) mm(2)/s and ADC < 1.13 * 10(-3) mm(2)/s could differentiate
      cervical cancer from non-malignant tissues (AUC 0.773-0.908). CONCLUSIONS:
      Cervical cancer has low perfusion and diffusion IVIM characteristics with
      promising potential for tissue differentiation. KEY POINTS: * Diffusion-weighted
      MRI is increasingly applied in evaluation of cervical cancer. * Cervical cancer
      has distinctive perfusion and diffusion characteristics. * Intravoxel incoherent
      motion characteristics can differentiate cervical cancer from non-malignant
      uterine tissues.

PMID- 24744199
TI  - Assessment of renal tissue elasticity by acoustic radiation force impulse
      quantification with histopathological correlation: preliminary experience in
      chronic kidney disease.
AB  - OBJECTIVES: Chronic kidney disease (CKD), a progressive and irreversible
      pathological syndrome, is the major cause of renal failure. Renal fibrosis is the
      principal process underlying the progression of CKD. Acoustic radiation force
      impulse (ARFI) quantification is a promising noninvasive method for assessing
      tissue stiffness. We evaluated whether the technique could reveal renal tissue
      fibrosis in CKD patients. METHODS: ARFI assessments were performed in 45 patients
      with CKD referred for renal biopsies to measure cortical shear wave velocity
      (SWV). During measurement, a standardized method was employed, which aimed to
      minimize the potential impact of variation of transducer force, sampling error of
      non-cortical tissue and structural anisotropy of the kidney. Then SWV was
      compared to patients' CKD stage and pathological fibrosis indicators. RESULTS:
      ARFI could not predict the different stages of CKD. Spearman correlation analysis
      showed that SWV did not correlate with any pathological indicators of fibrosis.
      CONCLUSION: ARFI assesses tissue stiffness of CKD kidneys by measuring cortical
      SWV. However, SWV did not show significant correlations with CKD stage and
      fibrosis indicators despite using standardized measurement methods. We therefore
      suggest that it would be necessary to evaluate the effect of pathological
      complexity and tissue perfusion of the kidney on stiffness assessment in future
      studies. KEY POINTS: * Acoustic radiation force impulse (ARFI) can quantify
      tissue elasticity of CKD kidney. * Despite standardized measurement, ARFI
      estimated elasticity did not correlate with renal fibrosis. * Effects of
      pathological complexity and tissue perfusion on renal stiffness warrant further
      study.

PMID- 24744200
TI  - Quantification of myocardial blood flow using dynamic 320-row multi-detector CT
      as compared with 15O-H2O PET.
AB  - OBJECTIVES: This study introduces a method to calculate myocardium blood flow
      (MBF) and coronary flow reserve (CFR) using the relatively low-dose dynamic 320
      row multi-detector computed tomography (MDCT), validates the method against (15)O
      H2O positron-emission tomography (PET) and assesses the CFRs of coronary artery
      disease (CAD) patients. METHODS: Thirty-two subjects underwent both dynamic CT
      perfusion (CTP) and PET perfusion imaging at rest and during pharmacological
      stress. In 12 normal subjects (pilot group), the calculation method for MBF and
      CFR was established. In the other 13 normal subjects (validation group), MBF and
      CFR obtained by dynamic CTP and PET were compared. Finally, the CFRs obtained by
      dynamic CTP and PET were compared between the validation group and CAD patients
      (n = 7). RESULTS: Correlation between MBF of MDCT and PET was strong (r = 0.95, P
      < 0.0001). CFR showed good correlation between dynamic CTP and PET (r = 0.67, P =
      0.0126). CFRCT in the CAD group (2.3 +/- 0.8) was significantly lower than that
      in the validation group (5.2 +/- 1.8) (P = 0.0011). CONCLUSIONS: We established a
      method for measuring MBF and CFR with the relatively low-dose dynamic MDCT. Lower
      CFR was well demonstrated in CAD patients by dynamic CTP. KEY POINTS: * MBF and
      CFR can be calculated using dynamic CTP with 320-row MDCT. * MBF and CFR showed
      good correlation between dynamic CTP and PET. * Lower CFR was well demonstrated
      in CAD patients by dynamic CTP.

PMID- 24744201
TI  - Chronic obstructive pulmonary disease (COPD) patients with osteoporotic vertebral
      compression fractures (OVCFs): improvement of pulmonary function after
      percutaneous vertebroplasty (VTP).
AB  - OBJECTIVES: To investigate the changes of respiratory function in patients
      affected by chronic obstructive pulmonary disease (COPD) with single dorsal
      osteoporotic vertebral compression fractures (OVCFs) treated with vertebroplasty
      (VTP). METHODS: Forty-five patients affected by COPD and single dorsal OVCF
      underwent VTP (29 men, 16 women; mean age 71.4 years, range 65-77 years).
      Inclusion criteria were magnetic resonance findings of bone marrow oedema,
      without intracanal bone fragments and refractory pain to medical treatment for at
      least 3 months. Osteoporosis was assessed by bone densitometry. Spirometry was
      performed before and after treatment. RESULTS: A significant VAS-score decrease
      was observed 1 week after VTP, with a subsequent decrease over time; vital
      capacity (VC) and forced vital capacity (FVC) improved over time, reaching a
      plateau at 3 months. Forced expiratory volume at 1 s (FEV1) did not significantly
      differ between the pre-VTP values and follow-up values. A significant correlation
      was observed between VAS-score values and VC, and VAS-score values and FVC. No
      significant correlation was observed between VAS-score values and FEV1 values.
      CONCLUSIONS: VTP improves restrictive ventilatory impairment in patients with
      moderate and severe COPD affected by single thoracic OVCFs. We recommend this
      treatment in the management of these patients. KEY POINTS: * Osteoporosis is a
      major comorbidity in chronic obstructive pulmonary disease (COPD) patients. *
      Pain due to osteoporotic vertebral compression fractures worsens respiratory
      failure in COPD. * Vertebroplasty improves ventilatory impairment in COPD
      patients with osteoporotic vertebral compression fractures.

PMID- 24744203
TI  - Time course of dichoptic masking in normals and suppression in amblyopes.
AB  - PURPOSE: To better understand the relationship between dichoptic masking in
      normal vision and suppression in amblyopia we address three questions: First,
      what is the time course of dichoptic masking in normals and amblyopes? Second, is
      interocular suppression low-pass or band-pass in its spatial dependence? And
      third, in the above two regards, is dichoptic masking in normals different from
      amblyopic suppression? METHODS: We measured the dependence of dichoptic masking
      in normal controls and amblyopes on the temporal duration of presentation under
      three conditions; monocular (the nontested eye-i.e., dominant eye of normals or
      nonamblyopic eye of amblyopes, being patched), dichoptic-luminance (the nontested
      eye seeing a mean luminance-i.e., a DC component) and dichoptic-contrast (the
      nontested eye seeing high-contrast visual noise). The subject had to detect a
      letter in the other eye, the contrast of which was varied. RESULTS: We found that
      threshold elevation relative to the patched condition occurred in both normals
      and amblyopes when the nontested eye saw either 1/f or band-pass filtered noise,
      but not just mean luminance (i.e., there was no masking from the DC component
      that corresponds to a channel responsive to a spatial frequency of 0 cyc/deg);
      longer presentation of the target (corresponding to lower temporal frequencies)
      produced greater threshold elevation. CONCLUSIONS: Dichoptic masking exhibits
      similar properties in both subject groups, being low-pass temporally and band
      pass spatially, so that masking was greatest at the longest presentation
      durations and was not greatly affected by mean luminance in the nontested eye.

PMID- 24744202
TI  - Reduction of circulating and selective limbic brain levels of (3alpha,5alpha)-3
      hydroxy-pregnan-20-one (3alpha,5alpha-THP) following forced swim stress in
      C57BL/6J mice.
AB  - RATIONALE: Stress activates the hypothalamic-pituitary-adrenal (HPA) axis, and
      GABAergic neuroactive steroids contribute to homeostatic regulation of this
      circuitry. Acute forced swim stress (FSS) increases plasma, cortical, and
      hypothalamic (3alpha,5alpha)-3-hydroxy-pregnan-20-one (3alpha,5alpha-THP) levels
      in rats. However, there have not been systemic investigations of acute stress on
      changes in plasma and brain levels of 3alpha,5alpha-THP in mouse models.
      OBJECTIVES: The present experiments aimed to assess circulating and local brain
      levels of 3alpha,5alpha-THP following acute FSS in C57BL/6J mice. METHODS: Mice
      were exposed to FSS (10 min), and 50 min later, blood and brains were collected.
      Circulating pregnenolone and 3alpha,5alpha-THP levels were assessed in serum.
      Free-floating brain sections (40 MUm, four to five sections/region) were
      immunostained and analyzed in cortical and limbic brain structures. RESULTS: FSS
      decreased circulating 3alpha,5alpha-THP (-41.6 +/- 10.4 %) and reduced
      3alpha,5alpha-THP immunolabeling in the paraventricular nucleus of the
      hypothalamus (-15.2 +/- 5.7 %), lateral amygdala (LA, -31.1 +/- 13.4 %), and
      nucleus accumbens (NAcc) shell (-31.9 +/- 14.6). Within the LA, vesicular
      glutamate transporter 1 (VGLUT1) and vesicular GABA transporter were localized in
      3alpha,5alpha-THP-positively stained cells, while in the NAcc shell, only VGLUT1
      was localized in 3alpha,5alpha-THP-positively stained cells, suggesting that both
      glutamatergic and GABAergic cells within the LA are 3alpha,5alpha-THP-positive,
      while in the NAcc shell, 3alpha,5alpha-THP only localizes to glutamatergic cells.
      CONCLUSIONS: The decrease in circulating and brain levels of 3alpha,5alpha-THP
      may be due to alterations in the biosynthesis/metabolism or changes in the
      regulation of the HPA axis following FSS. Changes in GABAergic neuroactive
      steroids in response to stress likely mediate functional adaptations in neuronal
      activity. This may provide a potential targeted therapeutic avenue to address
      maladaptive stress responsivity.

PMID- 24744204
TI  - FTY720 protects retinal ganglion cells in experimental glaucoma.
AB  - PURPOSE: To investigate the neuroprotective effects of sphingosine-1-phosphate
      (S1P) analogue fingolimod (FTY720) in experimental glaucoma in rats. METHODS: A
      unilateral chronic ocular hypertensive model was established by injections of
      microbeads into the anterior eye chamber of adult Sprague-Dawley rats. Fingolimod
      was administered to one group of rats intraperitoneally every week for 3 months.
      The scotopic threshold response (STR) was recorded to assess the function of the
      inner retina. Changes in cell density in the ganglion cell layer (GCL) were
      evaluated by hematoxylin and eosin staining on retinal sections and axonal count
      of the optic nerve was performed using Bielschowsky's silver staining. Effects of
      drug treatment on activation of Akt and Erk1/2 were evaluated using Western
      blotting by assessing phosphorylation levels of these proteins. The expression of
      S1P receptors in the optic nerve head region was also evaluated using Western
      blotting and immunohistochemistry. RESULTS: Administration of FTY720 reduced the
      loss of STR amplitude in glaucomatous eyes (P < 0.05). Counting and plotting the
      cell numbers/axonal density showed significant neural preservation in the GCL and
      the optic nerve (P < 0.05). An increased phosphorylation level of Akt and Erk1/2
      following FTY720 administration was observed. Both S1P1 and S1P5 receptors were
      found to be expressed in the retina and the expression of S1P1R was upregulated
      in experimentally-induced glaucoma. CONCLUSIONS: This study demonstrates, for the
      first time, that FTY720 could act as a neuroprotective agent to protect retinal
      ganglion cells in experimental glaucoma. Administration of this drug
      significantly reduces the structural and functional loss of the inner retina
      elicited indicating that it may potentially be used to attenuate neuronal loss
      and optic nerve damage in glaucomatous patients.

PMID- 24744205
TI  - Diffuse retinal nerve fiber layer defects identification and quantification in
      thickness maps.
AB  - PURPOSE: To report retinal nerve fiber layer (RNFL) defect identification and
      quantification in RNFL thickness maps according to the structural RNFL loss, and
      to evaluate diffuse RNFL defects. METHODS: A total of 170 patients with glaucoma
      and 186 normal subjects were consecutively enrolled. We defined RNFL defects in
      an RNFL thickness map by the degree of RNFL loss. The reference level for RNFL
      defect determination was set as a 20% to 70% degree of RNFL loss with a 1%
      interval. To identify RNFL defects, each individual RNFL thickness map was
      compared to the normative database map by using MATLAB software, and the region
      below the reference level was detected. The area, volume, location, and angular
      width of each RNFL defect were measured. Diffuse RNFL defects were defined as
      having an angular width > 30 degrees . RESULTS: The optimal reference level for
      glaucomatous RNFL defects identification was 42% loss of RNFL. Retinal nerve
      fiber layer defects were identified in all (100%) of the 170 glaucoma patients
      and false-positive RNFL defects were detected in 16 (8.16%) cases among the 186
      normal subjects. In all, 64.1% of glaucoma patients had diffuse RNFL defects, and
      47.7% of diffuse RNFL defects were associated with mild glaucoma patients. The
      volume of diffuse RNFL defects was significantly associated with the severity of
      glaucomatous damage (P = 0.009). Diffuse RNFL defects were located closer to the
      center of the optic disc than localized RNFL defects (P < 0.001). CONCLUSIONS:
      Retinal nerve fiber layer thickness map analysis is an effective method for
      analyzing RNFL defects. Quantitative measurements (area, volume, location, and
      width) were useful to understanding diffuse RNFL defects.

PMID- 24744206
TI  - Identification of the cellular mechanisms that modulate trafficking of frizzled
      family receptor 4 (FZD4) missense mutants associated with familial exudative
      vitreoretinopathy.
AB  - PURPOSE: Fifteen missense mutations in the frizzled family receptor 4 (FZD4)
      reported to cause familial exudative vitreoretinopathy (FEVR) were evaluated to
      establish the pathological cellular mechanism of disease and to explore novel
      therapeutic strategies. METHODS: The mutations were generated by site-directed
      mutagenesis and expressed in HeLa and COS-7 cell lines. Confocal fluorescence
      microscopy and N-glycosylation profiling were used to observe the subcellular
      localization of the mutant proteins relative to wild-type (WT).
      Polyubiquitination studies were used to establish the involvement of the
      proteasome. Culturing at reduced temperatures and incubation in the presence of
      chemical compounds were used to enhance mutant protein processing and exit out of
      the endoplasmic reticulum (ER). RESULTS: Confocal fluorescence microscopy of the
      mutants showed three distinct subcellular localizations, namely, a plasma
      membrane pattern, an ER pattern, and a mixed pattern to both compartments.
      Confocal fluorescence microscopy and N-glycosylation profiling established the
      predominant ER localization of P33S, G36N, H69Y, M105T, M105V, C181R, C204R,
      C204Y, and G488D mutants. Coexpression of these mutants with WT FZD4 showed the
      inability of the mutants to trap WT FZD4. Culturing the expressing cells at
      reduced temperatures or in the presence of chemical agents directed at
      ameliorating protein misfolding resulted in partial rescue of trafficking defects
      observed for M105T and C204Y mutants. CONCLUSIONS: Defective trafficking
      resulting in haploinsufficiency is a major cellular mechanism for several
      missense FEVR-causing FZD4 mutants. Our findings indicate that this trafficking
      defect might be correctable for some mutants, which may offer opportunities for
      the development of novel therapeutics approaches for this condition.

PMID- 24744207
TI  - Virtual tissue engineering and optic pathways: plotting the course of the axons
      in the retinal nerve fiber layer.
AB  - PURPOSE: As part of a larger project on virtual tissue engineering of the optic
      pathways, we describe the conditions that guide axons extending from the retina
      to the optic nerve head and formulate algorithms that meet such conditions. To
      find the entrance site on the optic nerve head of each axon, we challenge the
      fibers to comply with current models of axonal pathfinding. METHODS: First, we
      build a retinal map using a single type of retinal ganglion cell (RGC) using
      density functions from the literature. Dendritic arbors are equated to receptive
      fields. Shape and size of retinal surface and optic nerve head (ONH) are defined.
      A computer model relates each soma to the corresponding entry point of its axon
      into the optic disc. Weights are given to the heuristics that guide the
      preference entry order in the nerve. RESULTS: Retinal ganglion cells from the
      area centralis saturate the temporal section of the disc. Retinal ganglion cells
      temporal to the area centralis curve their paths surrounding the fovea; some of
      these cells enter the disc centrally rather than peripherally. Nasal regions of
      the disc receive mixed axons from the far periphery of the temporal hemiretina,
      together with axons from the nasal half. The model plots the course of the axon
      using Bezier curves and compares them with clinical data, for a coincidence level
      of 86% or higher. CONCLUSIONS: Our model is able to simulate basic data of the
      early optic pathways including certain singularities and to mimic mechanisms
      operating during development, such as timing and fasciculation.

PMID- 24744208
TI  - Iris concavity, corneal biomechanics, and their correlations with ocular biometry
      in a cohort of 10- to 12-year-old UK school boys: baseline data.
AB  - PURPOSE: Pigment dispersion syndrome is associated with iris concavity. This
      study investigated the prevalence of iris concavity, defined as a measurement of
      <=-0.1 mm, in a cohort of 10- to 12-year-old boys, and explored the relationship
      between iris curvature and anterior segment biometry. Associations with corneal
      biomechanical parameters also were explored. METHODS: A cohort of school boys (n
      = 96) was recruited from a local school. Anterior segment optical coherence
      tomography (AS-OCT) was performed under accommodative and nonaccommodative
      conditions, and iris curvature quantified. Corneal hysteresis (CH) and corneal
      resistance factor (CRF) were measured with the ocular response analyzer (ORA).
      Noncontact axial biometry was performed using laser interferometry. RESULTS: The
      prevalence of iris concavity was 24% on distance fixation, increasing to 65% on
      accommodation. Variables significantly associated with nonaccommodating iris
      curvature were lens vault (P = 0.02) and mean keratometry (P = 0.02). For both
      variables acting jointly, R(2) = 0.30. Variables associated significantly with
      accommodating iris curvature were anterior chamber depth (P = 0.009), lens vault
      (P = 0.049), and mean scleral spur angle (P < 0.0001). For these three variables
      acting jointly, R(2) = 0.33. Significant association was found between CH and
      spur-to-spur distance (R(2) = 0.07, P = 0.025). CONCLUSIONS: Iris concavity was a
      common finding in this cohort and related to anterior segment biometric
      parameters. Further work is required to clarify whether anatomical differences
      exist between iris concavity seen in the adolescent eye and that found in adults
      with pigment dispersion syndrome.

PMID- 24744209
TI  - A pragmatic approach to study the groundwater quality suitability for domestic
      and agricultural usage, Saq aquifer, northwest of Saudi Arabia.
AB  - The present study deals with detailed hydrochemical assessment of groundwater
      within the Saq aquifer. The Saq aquifer which extends through the NW part of
      Saudi Arabia is one of the major sources of groundwater supply. Groundwater
      samples were collected from about 295 groundwater wells and analyzed for various
      physico-chemical parameters such as electrical conductivity (EC), pH,
      temperature, total dissolved solids (TDS), Na(+), K(+), Ca(2+), Mg(2+), CO3 (-),
      HCO3 (-), Cl(-), SO4 (2-), and NO3 (-). Groundwater in the area is slightly
      alkaline and hard in nature. Electrical conductivity (EC) varies between 284 and
      9,902 MUS/cm with an average value of 1,599.4 MUS/cm. The groundwater is highly
      mineralized with approximately 30 % of the samples having major ion
      concentrations above the WHO permissible limits. The NO3 (-) concentration varies
      between 0.4 and 318.2 mg/l. The depth distribution of NO3 (-) concentration shows
      higher concentration at shallow depths with a gradual decrease at deeper depths.
      As far as drinking water quality criteria are concerned, study shows that about
      33 % of samples are unfit for use. A detailed assessment of groundwater quality
      in relation to agriculture use reveals that 21 % samples are unsuitable for
      irrigation. Using Piper's classification, groundwater was classified into five
      different groups. Majority of the samples show Mix-Cl-SO4- and Na-Cl-types water.
      The abundances of Ca(2+) and Mg(2+) over alkalis infer mixed type of groundwater
      facies and reverse exchange reactions. The groundwater has acquired unique
      chemical characteristics through prolonged rock-water interactions, percolation
      of irrigation return water, and reactions at vadose zone. 

PMID- 24744210
TI  - An assessment of chemical contaminants in sediments from the St. Thomas East End
      Reserves, St. Thomas, USVI.
AB  - The St. Thomas East End Reserves or STEER is located on the southeastern end of
      the island of St. Thomas, USVI. The STEER contains extensive mangroves and
      seagrass beds, along with coral reefs, lagoons, and cays. Within the watershed,
      however, are a large active landfill, numerous marinas, resorts, various
      commercial activities, an EPA Superfund Site, and residential areas, all of which
      have the potential to contribute pollutants to the STEER. As part of a project to
      develop an integrated assessment for the STEER, 185 chemical contaminants were
      analyzed in sediments from 24 sites. Higher levels of chemical contaminants were
      found in Mangrove Lagoon and Benner Bay in the western portion of the study area.
      The concentrations of polychlorinated biphenyls (PCBs),
      dichlorodiphenyltrichloroethane (DDT), zinc, copper, lead, and mercury were above
      a NOAA Effects Range-Low (ERL) sediment quality guideline at one or more sites,
      indicating impacts may be present in more sensitive species or life stages.
      Copper at one site in Benner Bay was above a NOAA Effects Range-Median (ERM)
      guideline indicating effects on benthic organisms were likely. The antifoulant
      boat hull ingredient tributyltin (TBT) was found at the third highest
      concentration in the history of NOAA's National Status and Trends (NS&T) Program,
      which monitors the nation's coastal and estuarine waters for chemical
      contaminants and bioeffects. The results from this project will provide resource
      managers with key information needed to make effective decisions affecting coral
      reef ecosystem health and gauge the efficacy of restoration activities. 

PMID- 24744211
TI  - Blood levels of cadmium and lead in residents near abandoned metal mine areas in
      Korea.
AB  - We analyzed national data on blood lead levels (BLL) and blood cadmium levels
      (BCL) in residents living near 38 abandoned metal mining areas (n = 5,682, 18-96
      years old) in Korea that were collected by the first Health Effect Surveillance
      for Residents in Abandoned Metal mines (HESRAM) from 2008 to 2011. The geometric
      mean BCL and BLL were 1.60 MUg/L (95 % CI = 1.57-1.62 MUg/L) and 2.87 MUg/dL (95
      % CI = 2.84-2.90 MUg/dL), respectively, notably higher than levels in the general
      population in Korea and other countries. We found significantly higher BLL and
      BCL levels in people living within 2 km of an abandoned metal mine (n = 3,165,
      BCL = 1.87 MUg/L, BLL = 2.91 MUg/dL) compared to people living more than 2 km
      away (n = 2,517, BCL = 1.31 MUg/L, BLL = 2.82 MUg/dL; P < 0.0001) and to the
      general population values reported in the literature. 

PMID- 24744213
TI  - Quantification of saccharides in honey samples through surface-assisted laser
      desorption/ionization mass spectrometry using HgTe nanostructures.
AB  - Quantification of monosaccharides and disaccharides in five honey samples through
      surface-assisted laser desorption/ionization mass spectrometry (SALDI-MS) using
      HgTe nanostructures as the matrix and sucralose as an internal standard has been
      demonstrated. Under optimal conditions (1* HgTe nanostructure, 0.2 mM ammonium
      citrate at pH 9.0), the SALDI-MS approach allows detection of fructose and
      maltose at the concentrations down to 15 and 10 MUM, respectively. Without
      conducting tedious sample pretreatment and separation, the SALDI-MS approach
      allows determination of the contents of monosaccharides and disaccharides in
      honey samples within 30 min, with reproducibility (relative standard deviation
      <15%). Unlike only sodium adducts of standard saccharides detected, sodium
      adducts and potassium adducts with differential amounts have been found among
      various samples, showing different amounts of sodium and potassium ions in the
      honey samples. The SALDI-MS data reveal that the contents of monosaccharides and
      disaccharides in various honey samples are dependent on their nectar sources. In
      addition to the abundant amounts of monosaccharides and disaccharides,
      oligosaccharides in m/z range of 650 - 2700 are only detected in pomelo honey.
      Having advantages of simplicity, rapidity, and reproducibility, this SALDI-MS
      holds great potential for the analysis of honey samples. 

PMID- 24744212
TI  - Mapping antiretroviral drugs in tissue by IR-MALDESI MSI coupled to the Q
      Exactive and comparison with LC-MS/MS SRM assay.
AB  - This work describes the coupling of the IR-MALDESI imaging source with the Q
      Exactive mass spectrometer. IR-MALDESI MSI was used to elucidate the spatial
      distribution of several HIV drugs in cervical tissues that had been incubated in
      either a low or high concentration. Serial sections of those analyzed by IR
      MALDESI MSI were homogenized and analyzed by LC-MS/MS to quantify the amount of
      each drug present in the tissue. By comparing the two techniques, an agreement
      between the average intensities from the imaging experiment and the absolute
      quantities for each drug was observed. This correlation between these two
      techniques serves as a prerequisite to quantitative IR-MALDESI MSI. In addition,
      a targeted MS(2) imaging experiment was also conducted to demonstrate the
      capabilities of the Q Exactive and to highlight the added selectivity that can be
      obtained with SRM or MRM imaging experiments.

PMID- 24744214
TI  - [Predictors of positive surgical margins after nephron-sparing surgery for renal
      cell carcinoma: retrospective analysis on 298 consecutive patients].
AB  - OBJECTIVES: Aim of our study was to evaluate the predictive factors of positive
      surgical margins (PSM) in a cohort of patients who underwent partial nephrectomy
      (PN) for renal cell carcinoma. MATERIAL AND METHODS: We retrospectively evaluated
      our Institutional database of patients treated with open or laparoscopic PN
      between 200 and 2013. Categorical variables were compared using Pearson's chi
      square test and linear-by-linear association. Multivariable Cox analysis was used
      in order to evaluate independent predictors of PSM. RESULTS: Surgical margins
      were found to be negative in 274 out of 298 patients (91.9%), and the remaining
      24 (8.1%) patients had PSM at the final pathological exam. The median clinical
      size was significantly lower in patients with PSM than those with negative
      margins (2.6 vs. 3 cm, p=0.03). At univariable analysis, a shorter operative time
      (p=0.04), a malignant histotype (p=0.04) and higher Fuhrman grade (p=0.02) were
      observed in patients with positive surgical margins compared to those without
      PSM. At multivariable analysis, median tumor dimension (p=0.02), the malignant
      histotype (p=0.01) and the high Fuhrman grade (3-4) (p=0.01) were found to be
      independent predictive factors of PSM. CONCLUSIONS: The most important goal of
      any PN is to reach negative surgical margins. In our study, clinical tumor
      dimensions, malignant tumor histotype and the high Fuhrman grade demonstrated to
      be independent predictive factors of PSM after nephron sparing surgery for renal
      cell carcinoma. Other prospective, multi-institutional studies are needed in
      order to confirm these results.

PMID- 24744217
TI  - [5ARI and PSA: therapeutic aspects].
AB  - BACKGROUND: PSA modifications can be determined not only by the presence of a
      prostate neoplasm but also by other benign diseases such as inflammation and
      benign prostatic hyperplasia (BPH). CLINICAL DATA: In cases with progressive BPH
      under 5 alpha reductase inhibitors, we obtain a reduction of the risk to receive
      unnecessary prostate biopsies (related to an increase of PSA secondary to a
      progressive BPH). On the contrary, BPH patients in progression with an elevated
      PSA level, under monotherapy with alpha1 blockers, continue to have PSA
      modifications related to benign prostatic diseases, increasing the risk of other
      unnecessary biopsies for prostate neoplasm diagnosis. EVIDENCE: During 5 alpha
      reductase inhibitors, the reduction and the following stabilization of PSA levels
      to a new nadir value exclude the need of new evaluations or biopsies for the
      early diagnosis of prostate cancer. On the contrary, a confirmed increase of PSA
      levels over the nadir is associated with the risk of a clinically relevant
      prostate neoplasm and therefore it induces a bioptic procedure.

PMID- 24744216
TI  - [The value of surgical margins for clinical predictions and decisions following
      radical cystectomy for bladder cancer].
AB  - Radical cystectomy completed with an extended pelvic lymph node dissection
      represents the most adequate curative treatment for muscle-invasive bladder
      cancer. After surgery, the tumor should be considered as completely removed only
      if the pathologist finds negative surgical margins. However, although the
      presence of positive surgical margins (PSM) intuitively appears as a factor
      conditioning a poor prognosis, the studies published at data could not
      definitively confirm this relationship. This fact may be mainly attributed to the
      lack of statistical independence between the presence of PSM and other pathologic
      factors such as tumor stage and lymph node status, that are themselves well known
      predictors of poor prognosis.The incidence of PSM has been estimated to be 3-9%.
      Although the persistence of tumor at both urethral and ureteral margins has been
      correlated with an increased risk of local recurrence, only perivesical soft
      tissue PSM have been associated with a significantly reduced risk of cancer
      specific survival.Female gender, locally advanced cancer, presence of vascular
      invasion and rare/mixed histology have been recognized as consistent risk factors
      for soft tissue PSM. Although, to date, the predictive role of both number and
      location of PSM remains totally to be investigated, there is general agreement
      that patients found with soft tissue PSM at the time of radical cystectomy should
      be proposed for adjuvant strategies, including radiation and chemotherapy. In
      this direction, many recent studies suggest to include the status of surgical
      margins in the pathologic report of any radical cystectomy. 

PMID- 24744215
TI  - [Nephrolithiasis: metabolic defects and terapeutic implications].
AB  - Over the past 10 years, major progress has been made in the knowledge of urinary
      lithogenesis, including the potential pathogenetic role of Randall's plaques and
      renal tubular crystal retention. Urine supersaturation is the driving force of
      this process and can be induced by some risk factors, including low urine volume,
      high urinary excretion of calcium oxalate and uric acid and low urinary excretion
      of citrate. Primary hypercalciuria can be due to intestinal overabsorption renal
      leak and bone reabsorption of calcium. Prophilaxis is mainly conducted with
      thiazides and low calcium diet which is indicated only in the intestinal form.
      Primary hyperoxaluria is treated with pyridoxine and may require in the severe
      forms simultaneous renal and liver transplantation. Enteric hyperoxaluria is
      secondary to fatty acids malabsorption and requires diet, oral calcium and
      cholestiramine. Hyperuricosuria is caused by diet endogenous overproduction,
      mainly due to enzymatic defects or high renal excretion of uric acid. Urine
      alkalinization with K or K and Mg citrate can prevent stone formation even in
      idiopathic uric acid nephrolithiasis, in which a defect of urine acidification is
      supposed to be the main abnormality, and in hypocitraturic patients. Cystinuria
      is a rare inherited defect with an intense clinical impact. It can be classified
      in three forms and urinary stone formation is the role. Increased solubility and
      conversion of cystine in a more soluble form are the main goals of the
      prophylaxis which includes K citrate and thiol agents administration. Tiopronin
      is preferred to D-penicillamine due to its lower side effects. 

PMID- 24744218
TI  - Cavernous hemangioma of the posterior mediastinum with bony invasion.
AB  - We herein report a case of a cavernous hemangioma of the posterior mediastinum
      treated with surgical resection. Mediastinal hemangiomas are rare and diagnosis
      is difficult prior to operation. A 58-year-old female was referred to our
      hospital for back pain and a tumor in the left posterior mediastinum that was
      detected by chest computed tomography (CT). CT showed a tumor adjacent to the
      left side of the fifth thoracic vertebrae measuring 60 * 50 mm with invasion into
      and destruction of the 5th rib. The tumor was resected successfully via
      hemilaminectomy with costotransversectomy, and was revealed to be a cavernous
      hemangioma histologically. 1 year and 5 months after surgery, the patient was
      asymptomatic and without a recurrence. Hemangiomas are usually considered benign
      but sometimes behave aggressively with destruction of the neighboring structures.
      We consider en bloc resection to be safe and effective for aggressive cavernous
      hemangiomas of the posterior mediastinum.

PMID- 24744219
TI  - Which diet for prevention of type 2 diabetes? A meta-analysis of prospective
      studies.
AB  - No specific diet is recommended to prevent type 2 diabetes. We did a meta
      analysis of prospective cohort studies to assess the association between
      different diets and prevention of type 2 diabetes. We did a comprehensive search
      of multiple electronic databases (Medline, Scopus, EMBASE, and ISI web of
      knowledge) until August 2013 using predefined criteria. We included prospective
      cohort studies that evaluated the role of different diets in type 2 diabetes
      prevention. Studies were selected by 2 independent reviewers. We did random
      effects meta-analyses to determine the relative risk (RR) of incident diabetes
      associated with healthful dietary patterns. A total of 21,372 cases of incident
      diabetes, from 18 prospective studies, with 20 cohorts, in 4 world regions were
      identified. In the random-effect meta-analysis of the 20 cohorts, RR was 0.80 (95
      % confidence interval (CI) = 0.74-0.86, P < 0.001), with high heterogeneity (I
      (2) = 57 %, P = 0.001) and no evidence of publication bias (Egger's test, P =
      0.653). Exclusion of two cohorts produced identical RR (0.80, 95 % CI 0.76-0.84),
      with nonsignificant heterogeneity (I (2) = 9 %). The risk of incident diabetes
      did not appreciably change considering the geography (USA, Europe, and Asia), the
      duration of follow-up (<=10 and >10 years), and type of diets (Mediterranean and
      DASH, Dietary Approaches to Stop Hypertension, diets). There was a difference
      between at risk and general population (P = 0.0487), but the evidence was limited
      to two studies only. The results of our study demonstrate that several healthy
      diets are equally and consistently associated with a 20 % reduced risk of future
      type 2 diabetes.

PMID- 24744220
TI  - Development of EUCAST zone diameter breakpoints and quality control range for
      Staphylococcus aureus with ceftaroline 5-MUg disk.
AB  - This ceftaroline MIC/disk comparison study for Staphylococcus aureus was
      performed for the purpose of establishing EUCAST zone diameter breakpoints.
      Ceftaroline susceptibility for a challenge set of 70 methicillin resistant- and
      30 methicillin susceptible-S. aureus was determined by 5-MUg disk diffusion and
      broth microdilution methods. Seventeen isolates were retested by disk and MIC,
      and the remaining 83 isolates were retested by MIC. Molecular testing was
      performed on 19 isolates with borderline susceptible ceftaroline MIC results to
      assess any differences in mecA and epidemiological correlation. An additional set
      of 101 consecutive clinical S. aureus isolates were tested using the 5-MUg disk.
      S. aureus ATCC 29213 was tested by multiple sites and media for QC range
      determination. Replicate MIC results were within +/-1 doubling dilution, with
      tendency for slightly lower repeat MICs, and there was minimal variation in
      replicate zone results. Based on susceptible breakpoints for MIC of <=1 mcg/mL
      and for disk of >20 mm, there was 100 % categorical agreement for 30 MSSA and 92
      % categorical agreement for 70 MRSA. There were no common MLST or PBP changes for
      strains with MICs of 1 and 2 mcg/mL. All ceftaroline disk results for the
      consecutively collected isolates were >20 mm. EUCAST selected the ceftaroline 5
      MUg disk breakpoint of Susceptible >=20, Resistant <20 mm because it correlated
      best with the MIC breakpoint of Susceptible <=1, Resistant >1 mg/L. A ceftaroline
      5-MUg disk QC range for S. aureus ATCC 29213 of 24-30 mm was also established by
      EUCAST.

PMID- 24744221
TI  - Improving liveweight gain of lambs infected by multidrug-resistant nematodes
      using a FECRT-based schedule of treatments.
AB  - The aim of this study was to compare the liveweight gain of lambs, infected by
      multidrug-resistant nematodes, treated by conventional schemes of helminth
      control or using a schedule based on fecal egg count reduction test (FECRT). The
      flock was selected after a FECRT (experiment 1) which revealed a parasite
      population resistant to benzimidazoles, imidazothiazoles, macrocyclic lactones
      (ivermectin), salicylanilides, nitrophenols, and organophosphates. Despite the
      parasite resistance to ivermectin (an avermectin), the moxidectin (a milbemycin)
      was effective against the gastrointestinal nematodes (PR > 90%). In experiment 2,
      48 suckling lambs were distributed in four randomized blocks (G1, G2, G3, and G4)
      by previous body weighings. G1 was kept as untreated control; G2 was treated
      following a FECRT-based schedule with drugs chosen based on fecal analysis (first
      drench with moxidectin, second drench with a combination of moxidectin and
      levamisole, and third drench with praziquantel, an anti-cestode drug); G3 and G4
      received three drenches with ivermectin or disophenol, respectively. Body
      weighings and fecal analysis of these lambs were performed every 2 weeks over a
      98-day period. An effective control of gastrointestinal nematodes was obtained
      with two nematicidal drenches following the FECRT-based schedule of treatments.
      On the other hand, eggs per gram of feces (EPG) counts were no different among
      untreated control, G3, and G4. Lambs treated using the FECRT-based schedule had
      the greatest liveweight gain among the groups tested. Additionally, liveweight
      gain was no different among the groups G3, G4, and G1. The FECRT-based schedule
      of anthelmintic treatments was beneficial regarding productivity and
      sustainability of helminth control in lambs infected by multidrug-resistant
      nematodes.

PMID- 24744222
TI  - Frequency of potentially inappropriate prescriptions in older people at discharge
      according to Beers and STOPP criteria.
AB  - BACKGROUND: Potentially inappropriate prescriptions (PIP) are frequent, generate
      negative outcomes, and are to a great extent avoidable. Although there is general
      agreement about the definition of PIP, how to measure them is a matter of debate.
      OBJECTIVE: Our aim was to measure the frequency of PIP in older people at
      hospital discharge using two sets of criteria--Beers (2012 update) and STOPP.
      SETTING: A university hospital in southern Spain. METHOD: This cross sectional
      study involved a random sample of patients 65 years or more discharged from the
      University Hospital San Cecilio (Granada, Spain), from July 1, 2011 to June 30,
      2012. Age, gender, length of hospital stay, type of hospital service, drugs
      prescribed and pathologies were obtained from discharge reports. MAIN OUTCOME
      MEASURE: The main outcome measures were: (1) the prevalence of PIP according to
      each set of criteria (Beers and STOPP) and its 95 % confidence interval, globally
      and stratified for different categories of the study variables; (2) the degree of
      agreement between the two criteria using Kappa statistics; and (3) the drugs most
      commonly involved in PIP according to both criteria. RESULTS: There were 624
      patients (median age 78) included in our study. According to Beers criteria, 22.9
      % (19.6-26.2 %) of the patients had at least one PIP. This figure was 38.4 %
      (34.6-42.2 %) for STOPP criteria. Just 13.6 % of the patients had prescriptions
      simultaneously inappropriate for both criteria. Higher PIP frequency was observed
      in patients discharged from internal medicine. PIP increased with the Charlson
      Index and with the number of drugs prescribed, but not with gender, age or length
      of hospital stay. CONCLUSION: A very high frequency of PIP at discharge was
      observed. By intervening in five drug groups, about 80 % of PIP might be avoided
      according to either of the two criteria.

PMID- 24744223
TI  - Role of metastasectomy for metastatic renal cell carcinoma in the era of targeted
      therapy.
AB  - Numerous biological pathways are affected in renal cell carcinoma and the
      introduction of targeted agents has improved the survival of patients with
      advanced and metastatic disease. Durable and long-lasting cure is rarely
      achieved, and in select cases, the excision of metastatic deposits has shown to
      increase survival. Clinical trials of targeted agents are being explored as
      neoadjuvant and adjuvant therapies with the role of metastasectomy evolving in
      the treatment paradigm. This review examines published reports of metastasectomy
      and its developing role in the era of targeted therapy. A Medline search was
      conducted using keywords "metastasectomy," "renal cell carcinoma," and "targeted
      therapy," and selected articles are discussed by examining prognostic
      stratification and metastasectomy in major anatomic regions. Most published
      reports span earlier periods of immunotherapy and chemotherapy, and henceforth,
      discussions are in historical context in this review. Although there is lack of
      Level 1 evidence, reports have suggested the prognostic value and survival
      benefit for metastasectomy in lesions that are amenable to complete resection
      after longer disease-free intervals in carefully selected patients with adequate
      performance status. Therefore, the role of metastasectomy must be further
      elucidated in the era of targeted therapy.

PMID- 24744224
TI  - Management, pathology and outcomes of Bosniak category IIF and III cystic renal
      lesions.
AB  - OBJECTIVE: To analyze the management, pathology and outcomes of Bosniak category
      IIF and III cystic renal lesions. METHODS: This retrospective study included 85
      consecutive patients with Bosniak category IIF and III lesions, who were actively
      surveilled or surgically treated at three academic urology centers between 2003
      and 2012. Outcomes of interest included the rates of cyst progression and
      pathology. RESULTS: Overall, 27 patients with Bosniak category IIF lesions were
      initially managed by active surveillance, from which eighteen (67 %) did not
      progress after a median interval of 64 months, while 9 (33 %) underwent surgery
      within a median interval of 18 months. There were 58 patients with Bosniak
      category III lesions, 54 (93 %) of which were managed by surgery. Compared with
      Bosniak category IIF, Bosniak category III lesions had more frequently proven RCC
      (64 vs. 30 %, p = 0.005). Of the tumors that underwent surgical extirpation, the
      T stage, grade (p = 0.65) and subtype distribution (p = 0.36) did not differ
      between the Bosniak categories. The majority of RCCs were low-stage and low-grade
      tumors. One patient developed a local recurrence. There were no RCC-specific
      deaths. CONCLUSIONS: As only a minority of Bosniak IIF lesions are malignant and
      the majority are low-stage and low-grade tumors, initial active surveillance is
      the standard of care for these lesions. Progressive Bosniak IIF lesions may
      undergo later RCC treatment without seemingly loosing the window of cure. Bosniak
      III lesions harbor a high risk of malignancy and should be managed as solid renal
      tumors according to contemporary guidelines.

PMID- 24744226
TI  - Molecular cloning and biochemical characterization of medaka (Oryzias latipes)
      lysosomal neu4 sialidase.
AB  - Glycoconjugates are known to be involved in many physiological events in
      vertebrates. Sialidase is one of the glycosidases, which removes sialic acid from
      glycoconjugates. In mammals, the properties and physiological functions of
      sialidases have been investigated, while there is little understanding of fish
      sialidase. Here, to investigate the significance of fish neu4 sialidase, neu4
      gene was cloned from medaka brain mRNA and identified. Sialidase-specific motifs
      (GPG, YRVP and Asp-Box) were well conserved in the medaka neu4 polypeptide.
      Optimal pH of medaka neu4 sialidase was 4.6, but its activity was sustained even
      at neutral and weak alkaline pH. The neu4 considerably cleaved sialic acid from 4
      methylumbelliferyl-N-acetyl-alpha-D-neuraminic acid and sialyllactose, but not
      from ganglioside and fetuin, which are good substrates for human NEU4. neu4
      activity was mostly detected in mitochondria/lysosome fraction after biochemical
      fractionation, and indirect immunofluorescence assays revealed neu4 localization
      in lysosome in neu4 overexpressed cells. Next, developmental change in medaka
      neu4 and other sialidase mRNA levels were estimated by real-time PCR. Each
      sialidases showed different expression patterns in embryonic development: neu4
      was up-regulated at late developmental stage in embryo, and neu3a mRNA level was
      quite high in 0.5 dpf. On the other hand, neu3b expression was drastically
      increased after hatching, suggesting that each sialidase may play a different
      role in embryonic development.

PMID- 24744227
TI  - Issues in nanocomposite ceramic engineering: focus on processing and properties
      of alumina-based composites.
AB  - Ceramic nanocomposites, containing at least one phase in the nanometric
      dimension, have received special interest in recent years. They have, in fact,
      demonstrated increased performance, reliability and lifetime with respect to
      monolithic ceramics. However, a successful approach to the production of tailored
      composite nanostructures requires the development of innovative concepts at each
      step of manufacturing, from the synthesis of composite nanopowders, to their
      processing and sintering.This review aims to deepen understanding of some of the
      critical issues associated with the manufacturing of nanocomposite ceramics,
      focusing on alumina-based composite systems. Two case studies are presented and
      briefly discussed. The former illustrates the benefits, in terms of sintered
      microstructure and related mechanical properties, resulting from the application
      of an engineering approach to a laboratory-scale protocol for the elaboration of
      nanocomposites in the system alumina-ZrO2-YAG (yttrium aluminium garnet). The
      latter illustrates the manufacturing of alumina-based composites for large-scale
      applications such as cutting tools, carried out by an injection molding process.
      The need for an engineering approach to be applied in all processing steps is
      demonstrated also in this second case study, where a tailored manufacturing
      process is required to obtain the desired results. 

PMID- 24744228
TI  - Effects of adding resorbable phosphate glass fibres and PLA to calcium phosphate
      bone cements.
AB  - BACKGROUND: Calcium phosphate cements (CPCs), due to their biocompatibility and
      degradation properties, are being widely investigated as a replacement to more
      commonly used polymethylmethacrylate (PMMA) for vertebroplasty. CPCs have shown
      the potential to be replaced by host bone tissue during the healing/remodelling
      process. However, brittleness and comparatively low strength restrict the use of
      CPC in load-bearing applications. Although porous CPC can integrate with bone
      over time, slow degradation profiles and poor interconnectivity between pores
      restricts osseointegration to the top layer of CPC only. METHODS: Polylactic acid
      (PLA) and phosphate glass fibres (PGFs) were incorporated in a CPC matrix to
      overcome the problem of inherent brittleness and limited osseointegration.
      RESULTS: Incorporation of PLA and PGFs within CPC was successful in achieving a
      much less brittle CPC matrix without affecting the mechanical properties of CPC.
      The area under the stress-strain curve showed that the total energy to failure of
      the CPC hybrid was significantly greater than that of the CPC control.
      CONCLUSIONS: The methodology adopted here to add PLA within the CPC matrix may
      also allow for incorporation of PLA cross-linked biochemicals. Micrographic
      studies revealed that it was possible to confer control over pore size, shape and
      interconnectivity without negatively affecting the mechanical properties of the
      cement. This tailorable porosity could potentially lead to better
      osseointegration within CPC.

PMID- 24744229
TI  - Cancellous bone response to strontium-doped hydroxyapatite in osteoporotic rats.
AB  - PURPOSE: The objective of this study was to investigate cancellous bone response
      to strontium-doped hydroxyapatite (SrHA) in ovariectomized (OVX) rats. METHODS:
      Hydroxyapatite (HA) and 10%SrHA (HA with 10 mol% calcium substituted by
      strontium) implants were prepared and characterized by scanning electronic
      microscopy (SEM), energy dispersive microanalysis (EDX) and X-ray diffraction
      (XRD). Twelve weeks after bilateral ovariectomy, 20 rats randomly received HA or
      10%SrHA implants in the right distal femur, with 10 animals in each group. Eight
      weeks after implantation, specimens were harvested and analyzed by micro-computed
      tomography (micro-CT) and histology. RESULTS: Compared with HA, 10%SrHA raised
      the percentage bone volume by 42.6%, bone-to-implant contact by 47.1%, mean
      trabecular number by 27.3%, mean trabecular thickness by 31.5% and mean
      connectivity density by 37.4%, while it decreased mean trabecular separation by
      20.1% in micro-CT evaluation. 10%SrHA also increased the bone area density by
      47.6% in histological analysis. CONCLUSIONS: With the HA implants as controls,
      the 10%SrHA implants were shown to increase bone density and bone-to-implant
      contact, and improve trabecular architecture in the vicinity of implant surfaces.

PMID- 24744230
TI  - Peripheral nerve regeneration inside collagen-based artificial nerve guides in
      humans.
AB  - PURPOSE: Nerve gap injuries may be associated with lesions in other structures,
      like tendons or bones; in these cases, it is common to plan a second surgery to
      improve functional recovery. Since macroscopic observations of nerve regeneration
      in humans are rare, we exploited these second surgeries for the purpose of
      studying nerve regeneration in humans. METHODS: We assessed the clinical outcomes
      of 50 implants of collagen-based nerve guides in the upper limb. We performed a
      second look at 20, assessing macroscopically both nerve regeneration and collagen
      degradation. RESULTS AND CONCLUSIONS: Pain was never recorded in these patients.
      An adequate sensory recovery took place whenever nerve regeneration was found
      inside the guide. Motor recovery seemed to occur only when the gap lesion was
      shorter than 10 mm. The degree of degradation appeared to be variable and was not
      directly correlated with time; we hypothesize that it could be associated with
      the site of implantation. Such a large number of second looks in humans has never
      been previously reported in the literature.

PMID- 24744231
TI  - Nitric oxide release from polydimethylsiloxane-based polyurethanes.
AB  - Localized nitric oxide (NO) release from polymeric materials holds much promise
      for the prevention of coagulation often associated with implantable and
      extracorporeal blood-contacting devices. Films of polyurethane (PU) containing
      incorporated polyethyleneimine were thus exposed to NO gas to form
      diazeniumdiolates (NONOates) in situ. Donor incorporation and NO gas exposure did
      not affect the mechanical properties of the films. The NO release capacity
      increased with increasing polydimethylsiloxane (PDMS) content in the soft segment
      of the PU: total capacity could be more than doubled (P<0.05) from 0.093 +/-
      0.028 to 0.225 +/- 0.004 mmol/g when the PDMS content was increased from 0 to
      100%. Release kinetics were best approximated using a modified Korsemeyer-Peppas
      power law (R2=0.95-0.99). Despite the resultant rapid initial decrease in NO
      release rates, values above that observed for quiescent endothelial cells (0.83
      pmol.cm(-2).s(-1)) were maintained for extended periods of 5-10 days, while rates
      above that of a stimulated endothelium (2.7-6.8 pmol.cm(-2).s(-1)) were achieved
      for the first 24 hours. This method of NONOate formation may be advantageous, as
      potential premature NO release by exposure of diazeniumdiolated donors during
      incorporation, processing and storage, can be avoided by in situ
      diazoniumdiolation closer to the time of implantation.

PMID- 24744232
TI  - Biocompatibility of MG-63 cells on collagen, poly-L-lactic acid, hydroxyapatite
      scaffolds with different parameters.
AB  - PURPOSE: In this study, osteoblast-like MG-63 cells were cultured on 3 different
      scaffold types composed of (a) collagen + poly-L-lactic acid (PLLA), (b) collagen
      + hydroxyapatite (HA; 30oC) or (c) collagen + hydroxyapatite (HA; 37oC) and
      produced with different porosities. METHODS: Biomechanical properties of the
      scaffolds were characterized by tensile strength measurements. Properties of the
      cell-seeded scaffolds were evaluated with scanning electron microscopy (SEM).
      Cell adhesion and proliferation capacities were evaluated. Alkaline phosphatase
      (ALP) levels in media were measured. Transmission electron microscopy (TEM) and
      histological analyses were used to assess morphological characteristics. RESULTS:
      Our results showed that collagen-based PLLA and HA scaffolds have good cell
      biocompatibility. MTT test showed that the scaffolds exhibited no cytotoxicity.
      According to the force and displacement data, collagen + HA at 37oC showed the
      highest mechanical strength and displacement. CONCLUSION: The results suggest
      that collagen-based PLLA and HA scaffolds might improve osteoblastic growth in
      vitro and have biomaterial integration potential in possible therapeutic
      approaches for future clinical studies.

PMID- 24744233
TI  - Structural behavior of human lumbar intervertebral disc under direct shear.
AB  - PURPOSE: The intervertebral disc (IVD) is a complex, flexible joint between
      adjacent vertebral bodies that provides load transmission while permitting
      movements of the spinal column. Finite element models can be used to help clarify
      why and how IVDs fail or degenerate. To do so, it is of importance to validate
      those models against controllable experiments. Due to missing experimental data,
      shear properties are not used thus far in validating finite element models. This
      study aimed to investigate the structural shear properties of human lumbar IVDs
      in posteroanterior (PA) and laterolateral (LL) loading directions. METHODS:
      Fourteen lumbar IVDs (median age: 49 years) underwent direct shear in PA and LL
      loading directions. A custom-build shear device was used in combination with a
      materials testing machine to load the specimens until failure. Shear stiffness,
      ultimate shear force and displacement, and work to failure were determined.
      RESULTS: Each specimen was tested until complete or partial disruption. Median
      stiffness in PA direction was 490 N/mm and in LL direction 568 N/mm. Median
      ultimate shear force in the PA direction was 2,877 N and in the LL direction
      3,199 N. Work to failure was 12 Nm in the PA and 9 Nm in the LL direction.
      CONCLUSIONS: This study was an experiment to subject IVDs to direct shear. The
      results could help us to understand the structure and function of IVDs with
      regard to mechanical spinal stability, and they can be used to validate finite
      element models of the IVD.

PMID- 24744234
TI  - Ultrastructural analysis of nanoparticles and ions released in periprosthetic
      membranes.
AB  - PURPOSE: The distribution and relationship of hydroxyapatite debris, nanometric
      organic and metal wear particles and metal ions on periimplant interface
      membranes following aseptic and septic arthroplastic loosening were investigated.
      METHODS: Scanning electron microscopy and X-ray spectroscopic analysis were used
      to analyze debris and ion distribution. RESULTS: Hydroxyapatite debris appeared
      with different morphology in a particular distribution among several membranes.
      These differences may reflect the occurrence of different friction forces taking
      place between prosthesis and bone interface in the several types of prostheses
      studied. Metal wear particles were detected in greater numbers in membranes from
      noncemented prostheses compared with those from cemented ones. In contrast, more
      organic particles were present in membrane from cemented prosthesis. No
      differences were observed between aseptic and septic membranes. CONCLUSION: Our
      findings support the need to evaluate the occurrence of friction forces that
      periprosthetic bone debris production may induce to exacerbate cellular
      reactivity. Furthermore, cellular engulfment of debris and the high level of
      different ions released indicate the occurrence of a toxic environment that may
      induce failure of any reparative pathways.

PMID- 24744235
TI  - Surgeon practices regarding infection prevention for growth friendly spinal
      procedures.
AB  - PURPOSE: The rate of infection in patients having growth sparing surgery for
      early onset scoliosis has been reported up to 25 % during the course of
      treatment. A recent study demonstrated significant variability in the approach to
      infection prevention in adolescent and neuromuscular scoliosis. The purpose of
      this study is to conduct a similar survey in order to understand approaches used
      by experienced pediatric spinal surgeons with regard to infection prevention in
      growth friendly spinal procedures. MATERIALS AND METHODS: After preliminary
      internal testing of a survey by the authors, a final 21-question survey was
      created and approved by the authors and electronically distributed to all members
      of the Chest Wall Spinal Deformity Study Group and the Growing Spine Study Group
      (n = 57). A total of 40 responses were obtained (70 %). RESULTS: Significant
      variability in practice was demonstrated across the majority of the questions
      answered. Several of the questions demonstrated relative equipoise between
      practices, including preoperative MRSA screening, preoperative chlorhexidine
      baths, postoperative antibiotic duration after insertion, use of topical
      antibiotics, use of drains, use of IV gram negative coverage or vancomycin, and
      skin preparation. CONCLUSION: Other studies have demonstrated that variability in
      practice may have a negative impact on clinical outcomes, so one could postulate
      that steps that can reduce variability in the current population may help improve
      outcomes in this population. Areas of clinical equipoise can be used to help
      design and direct multicenter studies with an ultimate goal of reducing
      infections in this population. LEVEL OF EVIDENCE: Level V.

PMID- 24744236
TI  - Synthesis of an oligonucleotide-derivatized amphipol and its use to trap and
      immobilize membrane proteins.
AB  - Amphipols (APols) are specially designed amphipathic polymers that stabilize
      membrane proteins (MPs) in aqueous solutions in the absence of detergent. A8-35,
      a polyacrylate-based APol, has been grafted with an oligodeoxynucleotide (ODN).
      The synthesis, purification and properties of the resulting 'OligAPol' have been
      investigated. Grafting was performed by reacting an ODN carrying an amine
      terminated arm with the carboxylates of A8-35. The use of OligAPol for trapping
      MPs and immobilizing them onto solid supports was tested using bacteriorhodopsin
      (BR) and the transmembrane domain of Escherichia coli outer membrane protein A
      (tOmpA) as model proteins. BR and OligAPol form water-soluble complexes in which
      BR remains in its native conformation. Hybridization of the ODN arm with a
      complementary ODN was not hindered by the assembly of OligAPol into particles,
      nor by its association with BR. BR/OligAPol and tOmpA/OligAPol complexes could be
      immobilized onto either magnetic beads or gold nanoparticles grafted with the
      complementary ODN, as shown by spectroscopic measurements, fluorescence
      microscopy and the binding of anti-BR and anti-tOmpA antibodies. OligAPols
      provide a novel, highly versatile approach to tagging MPs, without modifying them
      chemically nor genetically, for specific, reversible and targetable
      immobilization, e.g. for nanoscale applications. 

PMID- 24744237
TI  - Entrapment of DNA in an intersubunit tunnel system of a single-stranded DNA
      binding protein.
AB  - Instead of a classical single-stranded deoxyribonuleic acid (DNA)-binding protein
      (SSB), some hyperthermophilic crenarchaea harbor a non-canonical SSB termed
      ThermoDBP. Two related but poorly characterized groups of proteins, which share
      the ThermoDBP N-terminal DNA-binding domain, have a broader phylogenetic
      distribution and co-exist with ThermoDBPs and/or other SSBs. We have investigated
      the nucleic acid binding properties and crystal structures of representatives of
      these groups of ThermoDBP-related proteins (ThermoDBP-RPs) 1 and 2. ThermoDBP-RP
      1 and 2 oligomerize by different mechanisms and only ThermoDBP-RP2 exhibits
      strong single-stranded DNA affinity in vitro. A crystal structure of ThermoDBP
      RP2 in complex with DNA reveals how the NTD common to ThermoDBPs and ThermoDBP
      RPs can contact the nucleic acid in a manner that allows a symmetric
      homotetrameric protein complex to bind single-stranded DNA molecules
      asymmetrically. While single-stranded DNA wraps around the surface or binds along
      channels of previously investigated SSBs, it traverses an internal, intersubunit
      tunnel system of a ThermoDBP-RP2 tetramer. Our results indicate that some archaea
      have acquired special SSBs for genome maintenance in particularly challenging
      environments. 

PMID- 24744238
TI  - Different gene-specific mechanisms determine the 'revised-response' memory
      transcription patterns of a subset of A. thaliana dehydration stress responding
      genes.
AB  - Plants that have experienced several exposures to dehydration stress show
      increased resistance to future exposures by producing faster and/or stronger
      reactions, while many dehydration stress responding genes in Arabidopsis thaliana
      super-induce their transcription as a 'memory' from the previous encounter. A
      previously unknown, rather unusual, memory response pattern is displayed by a
      subset of the dehydration stress response genes. Despite robustly responding to a
      first stress, these genes return to their initial, pre-stressed, transcript
      levels during the watered recovery; surprisingly, they do not respond further to
      subsequent stresses of similar magnitude and duration. This transcriptional
      behavior defines the 'revised-response' memory genes. Here, we investigate the
      molecular mechanisms regulating this transcription memory behavior. Potential
      roles of abscisic acid (ABA), of transcription factors (TFs) from the ABA
      signaling pathways (ABF2/3/4 and MYC2), and of histone modifications (H3K4me3 and
      H3K27me3) as factors in the revised-response transcription memory patterns are
      elucidated. We identify the TF MYC2 as the critical component for the memory
      behavior of a specific subset of MYC2-dependent genes. 

PMID- 24744239
TI  - The Mus81-Mms4 structure-selective endonuclease requires nicked DNA junctions to
      undergo conformational changes and bend its DNA substrates for cleavage.
AB  - Mus81-Mms4/EME1 is a DNA structure-selective endonuclease that cleaves joint DNA
      molecules that form during homologous recombination in mitotic and meiotic cells.
      Here, we demonstrate by kinetic analysis using physically tethered DNA substrates
      that budding yeast Mus81-Mms4 requires inherent rotational flexibility in DNA
      junctions for optimal catalysis. Forster Resonance Energy Transfer experiments
      further reveal that recognition of 3'-flap and nicked Holliday junction
      substrates by Mus81-Mms4 involves induction of a sharp bend with a 100 degrees 
      angle between two duplex DNA arms. In addition, thiol crosslinking of Mus81-Mms4
      bound to DNA junctions demonstrates that the heterodimer undergoes a
      conformational change induced by joint DNA molecules with preferred structural
      properties. The results from all three approaches suggest a model for catalysis
      by Mus81-Mms4 in which initial DNA binding is based on minimal structural
      requirements followed by a rate-limiting conformational transition of the
      substrate and protein. This leads to a sharply kinked DNA molecule that may fray
      the DNA four base pairs away from the junction point to position the nuclease for
      cleavage between the fourth and fifth nucleotide. These data suggest that
      mutually compatible conformational changes of Mus81-Mms4 and its substrates
      tailor its incision activity to nicked junction molecules. 

PMID- 24744240
TI  - DNA-protein pi-interactions in nature: abundance, structure, composition and
      strength of contacts between aromatic amino acids and DNA nucleobases or
      deoxyribose sugar.
AB  - Four hundred twenty-eight high-resolution DNA-protein complexes were chosen for a
      bioinformatics study. Although 164 crystal structures (38% of those searched)
      contained no interactions, 574 discrete pi-contacts between the aromatic amino
      acids and the DNA nucleobases or deoxyribose were identified using strict
      criteria, including visual inspection. The abundance and structure of the
      interactions were determined by unequivocally classifying the contacts as either
      pi-pi stacking, pi-pi T-shaped or sugar-pi contacts. Three hundred forty-four
      nucleobase-amino acid pi-pi contacts (60% of all interactions identified) were
      identified in 175 of the crystal structures searched. Unprecedented in the
      literature, 230 DNA-protein sugar-pi contacts (40% of all interactions
      identified) were identified in 137 crystal structures, which involve C-H...pi
      and/or lone-pair...pi interactions, contain any amino acid and can be classified
      according to sugar atoms involved. Both pi-pi and sugar-pi interactions display a
      range of relative monomer orientations and therefore interaction energies (up to 
      50 (-70) kJ mol(-1) for neutral (charged) interactions as determined using
      quantum chemical calculations). In general, DNA-protein pi-interactions are more
      prevalent than perhaps currently accepted and the role of such interactions in
      many biological processes may yet to be uncovered.

PMID- 24744241
TI  - Mechanism of oxidant-induced mistranslation by threonyl-tRNA synthetase.
AB  - Aminoacyl-tRNA synthetases maintain the fidelity during protein synthesis by
      selective activation of cognate amino acids at the aminoacylation site and
      hydrolysis of misformed aminoacyl-tRNAs at the editing site. Threonyl-tRNA
      synthetase (ThrRS) misactivates serine and utilizes an editing site cysteine
      (C182 in Escherichia coli) to hydrolyze Ser-tRNA(Thr). Hydrogen peroxide oxidizes
      C182, leading to Ser-tRNA(Thr) production and mistranslation of threonine codons
      as serine. The mechanism of C182 oxidation remains unclear. Here we used a
      chemical probe to demonstrate that C182 was oxidized to sulfenic acid by air,
      hydrogen peroxide and hypochlorite. Aminoacylation experiments in vitro showed
      that air oxidation increased the Ser-tRNA(Thr) level in the presence of
      elongation factor Tu. C182 forms a putative metal binding site with three
      conserved histidine residues (H73, H77 and H186). We showed that H73 and H186,
      but not H77, were critical for activating C182 for oxidation. Addition of zinc or
      nickel ions inhibited C182 oxidation by hydrogen peroxide. These results led us
      to propose a model for C182 oxidation, which could serve as a paradigm for the
      poorly understood activation mechanisms of protein cysteine residues. Our work
      also suggests that bacteria may use ThrRS editing to sense the oxidant levels in
      the environment. 

PMID- 24744242
TI  - Eukaryotic and archaeal TBP and TFB/TF(II)B follow different promoter DNA bending
      pathways.
AB  - During transcription initiation, the promoter DNA is recognized and bent by the
      basal transcription factor TATA-binding protein (TBP). Subsequent association of
      transcription factor B (TFB) with the TBP-DNA complex is followed by the
      recruitment of the ribonucleic acid polymerase resulting in the formation of the
      pre-initiation complex. TBP and TFB/TF(II)B are highly conserved in structure and
      function among the eukaryotic-archaeal domain but intriguingly have to operate
      under vastly different conditions. Employing single-pair fluorescence resonance
      energy transfer, we monitored DNA bending by eukaryotic and archaeal TBPs in the
      absence and presence of TFB in real-time. We observed that the lifetime of the
      TBP-DNA interaction differs significantly between the archaeal and eukaryotic
      system. We show that the eukaryotic DNA-TBP interaction is characterized by a
      linear, stepwise bending mechanism with an intermediate state distinguished by a
      distinct bending angle. TF(II)B specifically stabilizes the fully bent TBP
      promoter DNA complex and we identify this step as a regulatory checkpoint. In
      contrast, the archaeal TBP-DNA interaction is extremely dynamic and TBP from the
      archaeal organism Sulfolobus acidocaldarius strictly requires TFB for DNA
      bending. Thus, we demonstrate that transcription initiation follows diverse
      pathways on the way to the formation of the pre-initiation complex. 

PMID- 24744243
TI  - Optimal guideRNAs for re-directing deaminase activity of hADAR1 and hADAR2 in
      trans.
AB  - Adenosine deaminases that act on RNA (ADAR) are a class of enzymes that catalyze
      the conversion of adenosine to inosine in RNA. Since inosine is read as guanosine
      ADAR activity formally introduces A-to-G point mutations. Re-addressing ADAR
      activity toward new targets in an RNA-dependent manner is a highly rational,
      programmable approach for the manipulation of RNA and protein function. However,
      the strategy encounters limitations with respect to sequence and codon contexts.
      Selectivity is difficult to achieve in adenosine-rich sequences and some codons,
      like 5'-GAG, seem virtually inert. To overcome such restrictions, we
      systematically studied the possibilities of activating difficult codons by
      optimizing the guideRNA that is applied in trans. We find that all 5'-XAG codons
      with X = U, A, C, G are editable in vitro to a substantial amount of at least 50%
      once the guideRNA/mRNA duplex is optimized. Notably, some codons, including CAG
      and GAG, accept or even require the presence of 5'-mismatched neighboring base
      pairs. This was unexpected from the reported analysis of global editing
      preferences on large double-stranded RNA substrates. Furthermore, we report the
      usage of guanosine mismatching as a means to suppress unwanted off-site editing
      in proximity to targeted adenosine bases. Together, our findings are very
      important to achieve selective and efficient editing in difficult codon and
      sequence contexts. 

PMID- 24744245
TI  - Toward the "ideal" inhibitor of NETs.

PMID- 24744244
TI  - Reward speeds up and increases consistency of visual selective attention: a
      lifespan comparison.
AB  - Children and older adults often show less favorable reward-based learning and
      decision making, relative to younger adults. It is unknown, however, whether
      reward-based processes that influence relatively early perceptual and attentional
      processes show similar lifespan differences. In this study, we investigated
      whether stimulus-reward associations affect selective visual attention
      differently across the human lifespan. Children, adolescents, younger adults, and
      older adults performed a visual search task in which the target colors were
      associated with either high or low monetary rewards. We discovered that high
      reward value speeded up response times across all four age groups, indicating
      that reward modulates attentional selection across the lifespan. This speed-up in
      response time was largest in younger adults, relative to the other three age
      groups. Furthermore, only younger adults benefited from high reward value in
      increasing response consistency (i.e., reduction of trial-by-trial reaction time
      variability). Our findings suggest that reward-based modulations of relatively
      early and implicit perceptual and attentional processes are operative across the
      lifespan, and the effects appear to be greater in adulthood. The age-specific
      effect of reward on reducing intraindividual response variability in younger
      adults likely reflects mechanisms underlying the development and aging of reward
      processing, such as lifespan age differences in the efficacy of dopaminergic
      modulation. Overall, the present results indicate that reward shapes visual
      perception across different age groups by biasing attention to motivationally
      salient events. 

PMID- 24744246
TI  - Genomic clues to ethnic differences in ALL.

PMID- 24744247
TI  - Jumping translocations and high-risk myeloma.

PMID- 24744248
TI  - Novel signaling axis in CML-initiating cells.

PMID- 24744249
TI  - cIAPs and XIAP reduce RIPKs to silence.

PMID- 24744250
TI  - Platelets join the world of "Omics".

PMID- 24744253
TI  - Core curriculum illustration: blunt traumatic mesenteric injury.

PMID- 24744252
TI  - Pituitary adenylate cyclase activating polypeptide (PACAP) dilates cerebellar
      arteries through activation of large-conductance Ca(2+)-activated (BK) and ATP
      sensitive (K ATP) K (+) channels.
AB  - Pituitary adenylate cyclase activating polypeptide (PACAP) is a potent
      vasodilator of numerous vascular beds, including cerebral arteries. Although
      PACAP-induced cerebral artery dilation is suggested to be cyclic AMP (cAMP)
      dependent, the downstream intracellular signaling pathways are still not fully
      understood. In this study, we examined the role of smooth muscle K(+) channels
      and hypothesized that PACAP-mediated increases in cAMP levels and protein kinase
      A (PKA) activity result in the coordinate activation of ATP-sensitive K(+) (KATP)
      and large-conductance Ca(2+)-activated K(+) (BK) channels for cerebral artery
      dilation. Using patch-clamp electrophysiology, we observed that PACAP enhanced
      whole-cell KATP channel activity and transient BK channel currents in freshly
      isolated rat cerebellar artery myocytes. The increased frequency of transient BK
      currents following PACAP treatment is indicative of increased intracellular
      Ca(2+) release events termed Ca(2+) sparks. Consistent with the electrophysiology
      data, the PACAP-induced vasodilations of cannulated cerebellar artery
      preparations were attenuated by approximately 50 % in the presence of
      glibenclamide (a KATP channel blocker) or paxilline (a BK channel blocker).
      Further, in the presence of both blockers, PACAP failed to cause vasodilation. In
      conclusion, our results indicate that PACAP causes cerebellar artery dilation
      through two mechanisms: (1) KATP channel activation and (2) enhanced BK channel
      activity, likely through increased Ca(2+) spark frequency. 

PMID- 24744254
TI  - Erratum to: Do Neighborhood Attributes Moderate the Relationship Between Alcohol
      Establishment Density and Crime?

PMID- 24744255
TI  - Lack of response to artificial selection on developmental stability of partial
      wing shape components in Drosophila melanogaster.
AB  - Developmental stability, the ability of organisms to buffer their developmental
      processes against developmental noise is often evaluated with fluctuating
      asymmetry (FA). Natural genetic variation in FA has been investigated using
      Drosophila wings as a model system and the recent estimation of the heritability
      of wing shape FA was as large as 20%. Because natural genetic variation in wing
      shape FA was found to localize in a partial component of the wings, heritable
      variation in specific parts of the wings might be responsible for FA estimation
      based on the whole wing shape. In this study, we quantified the shape of three
      partial components of the wings, and estimated the heritability of the wing shape
      FA based on artificial selections. As a result, FA values for the partial wing
      shape components did not respond to artificial selections and the heritability
      scores estimated were very small. These results indicate that natural additive
      genetic variation in FA of partial wing components was very small compared with
      that in a complex wing trait.

PMID- 24744256
TI  - Conditions for the validity of SNP-based heritability estimation.
AB  - The heritability of a trait (h(2)) is the proportion of its population variance
      caused by genetic differences, and estimates of this parameter are important for
      interpreting the results of genome-wide association studies (GWAS). In recent
      years, researchers have adopted a novel method for estimating a lower bound on
      heritability directly from GWAS data that uses realized genetic similarities
      between nominally unrelated individuals. The quantity estimated by this method is
      purported to be the contribution to heritability that could in principle be
      recovered from association studies employing the given panel of SNPs (h(2)(SNP)).
      Thus far, the validity of this approach has mostly been tested empirically. Here,
      we provide a mathematical explication and show that the method should remain a
      robust means of obtaining h(2)(SNP)) under circumstances wider than those under
      which it has so far been derived.

PMID- 24744257
TI  - Patient level costing in Ireland: process, challenges and opportunities.
AB  - BACKGROUND: In 2013, the Department of Health released their policy paper on
      hospital financing entitled Money Follows the Patient. A fundamental building
      block for the proposed financing model is patient level costing. AIM: This paper
      outlines the patient level costing process, identifies the opportunities and
      considers the challenges associated with the process in the Irish hospital
      setting. METHODS: Methods involved a review of the existing literature which was
      complemented with an interview with health service staff. RESULTS: There are
      considerable challenges associated with implementing patient level costing
      including deficits in information and communication technologies and financial
      expertise as well as timeliness of coding. In addition, greater clinical input
      into the costing process is needed compared to traditional costing processes.
      However, there are long-term benefits associated with patient level costing;
      these include empowerment of clinical staff, improved transparency and price
      setting and greater fairness, especially in the treatment of outliers. These can
      help to achieve the Government's Health Strategy. CONCLUSIONS: The benefits of
      patient level costing need to be promoted and a commitment to investment in
      overcoming the challenges is required.

PMID- 24744258
TI  - Allergy in Irish adults: a survey of referrals and outcomes at a major centre.
AB  - BACKGROUND: There is an increasing demand for specialist public allergy services
      across Ireland. Little data exist on the patterns of allergic disease in Irish
      adults. The limited resources available require innovative strategies to ensure
      quality care delivery. AIMS: This study aimed to review the types of allergy
      referrals and diagnostic outcomes at a major Irish centre, and to establish an
      efficient method of communication with non-specialist practitioners. METHODS:
      Demographic data, referral characteristics and diagnostic outcomes from one
      hundred consecutive new allergy referrals were identified. Additionally,
      communications to a pilot email service were reviewed over a 12-month period and
      user satisfaction assessed. RESULTS: Requests for the investigation of food
      allergy accounted for 71% of referrals. Despite this, the main diagnostic outcome
      in this cohort was a non-allergic condition, chronic spontaneous urticaria (56%).
      immunoglobulin E (IgE)-mediated food allergy was definitively diagnosed in only
      9% of patients, with the majority of these presenting with anaphylaxis. The
      allergy advice email service received 43 requests for assistance over 12 months,
      mainly for help in the interpretation of an allergy clinical history. Feedback on
      the email service was universally positive. CONCLUSIONS: The majority of patients
      in this cohort did not have IgE-mediated allergic disease. Increased awareness of
      the features that differentiate allergy from non-allergic conditions such as food
      intolerance or chronic spontaneous urticaria is required. The allergy advice
      email service should be developed further to play a key role in education and
      care delivery in partnership primary care.

PMID- 24744259
TI  - Identifying hepatocellular carcinoma-related genes and pathways by system biology
      analysis.
AB  - BACKGROUND: Previous researches have been focused on revealing the functions of
      each individual gene and/or pathway in the initiation, progression and
      maintenance of hepatocellular carcinoma (HCC). However, the mechanistic
      relationships among different genes and/or pathways are largely unknown. AIMS: In
      this study, we tended to uncover the potential molecular networks and critical
      genes which play important roles in HCC progression. METHODS: The transcriptional
      profiles from normal and HCC patient samples were analyzed and compared using
      bioinformatic methods, including differentially expressed gene (DEG) analysis,
      hierarchical clustering, construction of protein-protein interaction (PPI)
      network and GO-Elite analysis. RESULTS: Initially, the normal and HCC sample data
      were processed and 679 most dramatic DEGs were identified. The PPI network
      analysis indicates the significance of multiple biological processes as well as
      signaling pathways in affecting liver function and HCC progression. In addition,
      hierarchical clustering analysis showed the most significant modules and
      identified the relationship between different genes, and some important genes
      such as FOS, IGF1, ADH4, ITGA2 and LEF1 were found to be hubs which master each
      individual module. CONCLUSION: Our study greatly improves the understanding of
      the HCC development in a systematic manner and provides the potential clue for
      exploiting drugs which might target the most significant genes and/or signaling
      pathways.

PMID- 24744260
TI  - Retrieval practice over the long term: should spacing be expanding or equal
      interval?
AB  - If multiple opportunities are available to review to-be-learned material, should
      a review occur soon after initial study and recur at progressively expanding
      intervals, or should the reviews occur at equal intervals? Landauer and Bjork
      (1978) argued for the superiority of expanding intervals, whereas more recent
      research has often failed to find any advantage. However, these prior studies
      have generally compared expanding versus equal-interval training within a single
      session, and have assessed effects only upon a single final test. We argue that a
      more generally important goal would be to maintain high average performance over
      a considerable period of training. For the learning of foreign vocabulary spread
      over four weeks, we found that expanding retrieval practice (i.e., sessions
      separated by increasing numbers of days) produced recall equivalent to that from
      equal-interval practice on a final test given eight weeks after training.
      However, the expanding schedule yielded much higher average recallability over
      the whole training period. 

PMID- 24744261
TI  - Performance of p16INK4a/Ki-67 immunocytochemistry for identifying CIN2+ in
      atypical squamous cells of undetermined significance and low-grade squamous
      intraepithelial lesion specimens: a Japanese Gynecologic Oncology Group study.
AB  - BACKGROUND: p16(INK4a) immunohistochemistry has revealed a high rate of
      positivity in cervical intraepithelial neoplasia grade 2 (CIN2) and more severe
      conditions (CIN2+). The Lower Anogenital Squamous Terminology Standardization
      project proposed p16(INK4a) immunohistochemistry as an ancillary test for CIN.
      Immunocytochemistry involving dual staining for p16(INK4a) and Ki-67 in the
      triage of atypical squamous cells of undetermined significance (ASCUS) and low
      grade squamous intraepithelial lesions (LSIL) is reported to be useful in the
      identification of CIN2+. However, it is unclear whether p16(INK4a)/Ki-67
      immunocytochemistry is of practical relevance for the triage of ASCUS and LSIL in
      the Japanese screening system. METHODS: From 427 women fulfilling the eligibility
      criteria, 188 ASCUS and 239 LSIL specimens were analyzed. The accuracy of
      p16(INK4a)/Ki-67 immunocytochemistry and genotyping of high-risk human
      papillomaviruses (HPVs) in detecting CIN2+ were compared. RESULTS: p16(INK4a)/Ki
      67 immunocytochemistry was positive in 33.5 % (63/188) of ASCUS, and 36.8 %
      (88/239) of LSIL specimens. The sensitivity and specificity of p16(INK4a)/Ki-67
      immunocytochemistry was 87.3 % (95 % confidence interval 78.0-93.8 %) and 76.4 %
      (71.6-80.8 %), respectively. The positive and negative predictive values were
      45.7 % (37.6-54.0 %) and 96.4 % (93.4-98.3 %), respectively; positive and
      negative likelihood ratios were 3.71 and 0.17, respectively. Using the McNemar
      test, p16(INK4a)/Ki-67 immunocytochemistry showed equivalent sensitivity but
      higher specificity than the HPV genotyping test CONCLUSIONS: Compared with high
      risk HPV genotyping, p16(INK4a)/Ki-67 immunocytochemistry was a more accurate
      triage test for identifying CIN2+ in ASCUS and LSIL specimens.

PMID- 24744262
TI  - Development of hypertension within 2 weeks of initiation of sorafenib for
      advanced hepatocellular carcinoma is a predictor of efficacy.
AB  - BACKGROUND: Sorafenib is an agent that inhibits vascular endothelial growth
      factor and is associated with onset or worsening of hypertension in some
      patients. We conducted a retrospective analysis of whether the development of
      hypertension during sorafenib treatment of advanced hepatocellular carcinoma
      could be a predictor of anti-cancer efficacy. METHODS: The study included 38
      patients with advanced hepatocellular carcinoma who had received sorafenib for at
      least 1 month between January 2010 and December 2012. A retrospective analysis of
      the efficacy of sorafenib was conducted by dividing the patients into two groups
      a hypertension group, presenting with grade 2 or higher hypertension according to
      the Common Terminology Criteria for Adverse Events (CTCTE) version 4.0; and a non
      hypertension group, which included all other patients. This study evaluated the
      occurrence of hypertension within 2 weeks of initiation of therapy in order to
      avoid any treatment duration bias. Images were evaluated using the modified
      Response Evaluation Criteria in Solid Tumors. The response rate, time to
      progression, and overall survival were assessed. RESULTS: Twenty-two patients (58
      %) developed grade 2 or higher hypertension within 2 weeks of initiation of
      therapy. The response rate was significantly higher in the hypertension group.
      Median time to progression was 153 days in the hypertension group versus 50.5
      days in the non-hypertension group, which was significantly longer in the
      hypertension group. Moreover, median overall survival was 1,329 days in the
      hypertension group versus 302 days in the non-hypertension group, which was
      significantly longer in the hypertension group. CONCLUSIONS: Hypertension within
      2 weeks of initiation of therapy may be a predictor of the anti-cancer efficacy
      of sorafenib when used for the treatment of advanced hepatocellular carcinoma.

PMID- 24744263
TI  - Reducing Emergency Medical Service response time via the reallocation of
      ambulance bases.
AB  - The demand for highly efficient and effective services and consumer goods is an
      essential prerequisite for modern organizations. In healthcare, efficiency and
      effectiveness mean reducing disabilities and maintaining human life. One
      challenge is guaranteeing rapid Emergency Medical Service (EMS) response. This
      study analyzes the EMS of Belo Horizonte, Brazil, using two modeling techniques:
      optimization and simulation. The optimization model locates ambulance bases and
      allocates ambulances to those bases. A simulation of this proposed configuration
      is run to analyze the dynamic behavior of the system. The main assumption is that
      optimizing the ambulance base locations can improve the system response time.
      Feasible solutions were found and the current system may be improved while
      considering economic and operational changes. 

PMID- 24744265
TI  - Cis-regulatory variation: significance in biomedicine and evolution.
AB  - Cis-regulatory regions (CRR) control gene expression and chromatin modifications.
      Genetic variation at CRR in individuals across a population contributes to
      phenotypic differences of biomedical relevance. This standing variation is
      important for personalized genomic medicine as well as for adaptive evolution and
      speciation. This review focuses on genetic variation at CRR, its influence on
      chromatin, gene expression, and ultimately disease phenotypes. In addition, we
      summarize our understanding of how this variation may contribute to evolution.
      Recent technological and computational advances have accelerated research in the
      direction of personalized medicine, combining strengths of molecular biology and
      genomics. This will pave new ways to understand how CRR variation affects
      phenotypes and chart out possible avenues of intervention. 

PMID- 24744264
TI  - Innate immune responses and neuroepithelial degeneration and regeneration in the
      mouse olfactory mucosa induced by intranasal administration of Poly(I:C).
AB  - The pathogenesis of postviral olfactory disorder (PVOD) has not been fully
      elucidated. We investigated morphological changes and innate immune responses in
      the mouse olfactory mucosa induced by intranasal administration of polyinosinic
      polycytidylic acid [Poly(I:C)], a synthetic analog of viral double-stranded RNA.
      Mice received three administrations of saline with or without Poly(I:C), once
      every 24 h. The olfactory mucosa was harvested at various intervals after the
      first administration (8 h, 3, 9 and 24 days). In the Poly(I:C) group, the number
      of apoptotic cells in the olfactory neuroepithelium had increased at 8 h. At 9
      days, the olfactory neuroepithelium had severely degenerated and behavioral tests
      demonstrated that the mice showed signs of olfactory deterioration. At 24 days,
      the structure of the neuroepithelium had regenerated almost completely. Regarding
      the innate immune responses, many neutrophils had infiltrated the olfactory
      neuroepithelium at 8 h and had exuded into the nasal cavity by 3 days.
      Macrophages had also infiltrated the olfactory neuroepithelium at 8 h although to
      a lesser extent, but they still remained in the neuroepithelium at 24 days.
      Poly(I:C)-induced neuroepithelial damage was significantly inhibited by a
      neutrophil elastase inhibitor and was suppressed in neutropenic model mice. These
      findings suggest that the secondary damage caused by the neutrophil-mediated
      innate immune response plays an important role in the pathogenesis of PVOD. 

PMID- 24744266
TI  - Impaired mitochondrial function and reduced viability in bone marrow cells of
      obese mice.
AB  - Bone marrow cells (BMCs) are the main type of cells used for transplantation
      therapies. Obesity, a major world health problem, has been demonstrated to affect
      various tissues, including bone marrow. This could compromise the success of such
      therapies. One of the main mechanisms underlying the pathogenesis of obesity is
      mitochondrial dysfunction, and recent data have suggested an important role for
      mitochondrial metabolism in the regulation of stem cell proliferation and
      differentiation. Since the potential use of BMCs for clinical therapies depends
      on their viability and capacity to proliferate and/or differentiate properly, the
      analysis of mitochondrial function and cell viability could be important
      approaches for evaluating BMC quality in the context of obesity. We therefore
      compared BMCs from a control group (CG) and an obese group (OG) of mice and
      evaluated their mitochondrial function, proliferation capacity, apoptosis, and
      levels of proteins involved in energy metabolism. BMCs from OG had increased
      apoptosis and decreased proliferation rates compared with CG. Mitochondrial
      respiratory capacity, biogenesis, and the coupling between oxidative
      phosphorylation and ATP synthesis were significantly decreased in OG compared
      with CG, in correlation with increased levels of uncoupling protein 2 and reduced
      peroxisome proliferator-activated receptor-coactivator 1alpha content. OG also
      had decreased amounts of the glucose transporter GLUT-1 and insulin receptor
      (IRbeta). Thus, Western-diet-induced obesity leads to mitochondrial dysfunction
      and reduced proliferative capacity in BMCs, changes that, in turn, might
      compromise the success of therapies utilizing these cells. 

PMID- 24744267
TI  - Temporal and spatial expression of caudal-type homeobox gene-2 during hindgut
      development in rat embryos with ethylenethiourea-induced anorectal malformations.
AB  - The main aim of this study was to determine Cdx2 expression patterns during
      anorectal development in normal and anorectal malformation (ARM) embryos with a
      view to establishing the possible role of Cdx2 in ARM pathogenesis. ARM was
      induced with ethylenethiourea on the 10th gestational day (GD10) in rat embryos,
      and Cesarean deliveries were performed to harvest the embryos. The temporal and
      spatial expression of Cdx2 was evaluated in normal rat embryos (n = 303) and ARM
      embryos (n = 321) from GD13 to GD16. Immunohistochemical staining revealed that,
      in normal embryos, Cdx2 was mainly expressed on the epithelium of the urorectal
      septum (URS) and the hindgut on GD13. On GD14, Cdx2-immunopositive cells were
      extensively detected on the URS, hindgut, and cloacal membrane. On GD15,
      increased immunopositive tissue staining on the anal membrane was evident. In ARM
      embryos, the epithelium of the cloaca, URS, and anorectum were negative or
      faintly immunostaining for Cdx2. Analyses by Western blot and real-time reverse
      transcription plus the polymerase chain reaction revealed that, in the normal
      group, Cdx2 protein and mRNA expression showed time-dependent changes in the
      developing hindgut from GD13 to GD16. Upon the URS division of the cloaca into
      the primitive rectum and urogenital sinus (UGS) on GD15, Cdx2 expression began to
      decrease. Moreover, the Cdx2 expression level in the ARM group from GD13 to GD14
      was significantly lower than that in the normal group (P < 0.05). In ARM embryos,
      an imbalance in the spatiotemporal expression of Cdx2 was noted during anorectal
      morphogenesis from GD13 to GD16. Downregulation of Cdx2 at the time of cloacal
      separation into the primitive rectum and UGS might thus be related to the
      development of ARM. 

PMID- 24744268
TI  - Chicken oviduct-the target tissue for growth hormone action: effect on cell
      proliferation and apoptosis and on the gene expression of some oviduct-specific
      proteins.
AB  - The aim of this study was to examine the in vivo effect of growth hormone (GH) on
      cell proliferation and apoptosis and on the gene expression of selected proteins
      in the chicken oviduct before sexual maturity (first oviposition). Ten-week-old
      Hy-Line Brown chickens were injected three times a week with 200 MUg . kg(-1)
      body weight of recombinant chicken GH (cGH) until 16 weeks of age. Control hens
      received 0.9 % NaCl with 0.05 % bovine serum albumin as a vehicle. Treatment with
      cGH increased (P < 0.05) oviduct weight at 16 weeks of age, i.e. 1-2 weeks before
      onset of egg laying. The highest number of proliferating (determined by
      proliferating cell nuclear antigen [PCNA] immunocytochemistry) and apoptotic
      (determined by TUNEL assay) cells in the oviduct was found in the mucosal
      epithelium, and the lowest in the stroma. Administration of cGH did not increase
      (P > 0.05) the number of PCNA-positive cells but it decreased (P < 0.01) the
      number of TUNEL-positive cells, thus increasing the proliferating-to-apoptotic
      cell ratio in the oviduct. Gene expression (determined by real-time polymerase
      chain reaction) of apoptosis-related caspase-2 in the magnum and caspase-3 in the
      magnum and isthmus and their activity (determined by fluorometric assay) in the
      magnum were attenuated (P < 0.05) in cGH-treated hens. The gene expression of the
      magnum-specific ovalbumin and the shell-gland-specific ovocalyxins 32 and 36 was
      increased (P < 0.05) in cGH-treated chickens. In contrast, the expression of Bcl
      2 and of caspases 8 and 9 was not affected by cGH in any of the oviductal
      segments. The results suggest that GH, via the orchestration of apoptosis and
      expression of some oviduct-specific proteins, participates in the development and
      activity of the chicken oviduct prior to the onset of egg laying. 

PMID- 24744269
TI  - Validation and refinement of the Disease Risk Index for allogeneic stem cell
      transplantation.
AB  - Because the outcome of allogeneic hematopoietic cell transplantation (HCT) is
      predominantly influenced by disease type and status, it is essential to be able
      to stratify patients undergoing HCT by disease risk. The Disease Risk Index (DRI)
      was developed for this purpose. In this study, we analyzed 13,131 patients
      reported to the Center for International Blood and Marrow Transplant Research who
      underwent HCT between 2008 and 2010. The DRI stratified patients into 4 groups
      with 2-year overall survival (OS) ranging from 64% to 24% and was the strongest
      prognostic factor, regardless of age, conditioning intensity, graft source, or
      donor type. A randomly selected training subgroup of 9849 patients was used to
      refine the DRI, using a multivariable regression model for OS. This refined DRI
      had improved prediction ability for the remaining 3282 patients compared with the
      original DRI or other existing schemes. This validated and refined DRI can be
      used as a 4- or 3-group index, depending on the size of the cohort under study,
      for prognostication; to facilitate the interpretation of single-center,
      multicenter, or registry studies; to adjust center outcome data; and to stratify
      patients entering clinical trials that enroll patients across disease categories.

PMID- 24744270
TI  - Invited commentary: recommendation for a north american pediatric patch test
      series.
AB  - Given the increased recognition of pediatric allergic contact dermatitis and lack
      of patch testing consensus in children, we present a minimum basic 20-allergen
      North American pediatric series, for screening children ages 6-12 with suspected
      contact allergy. 

PMID- 24744271
TI  - Metabolomics approach in allergic and rheumatic diseases.
AB  - Metabolomics is the analysis of the concentration profiles of low molecular
      weight compounds present in biological fluids. Metabolites are nonpeptide
      molecules representing the end products of cellular activity. Therefore, changes
      in metabolite concentrations reveal the range of biochemical effects induced by a
      disease or its therapeutic intervention. Metabolomics has recently become
      feasible with the accessibility of new technologies, including mass spectrometry
      and high-resolution proton nuclear magnetic resonance, and has already been
      applied to several disorders. Indeed, it has the advantage of being a nontargeted
      approach for identifying potential biomarkers, which means that it does not
      require a preliminary knowledge of the substances to be studied. In this review,
      we summarize the main studies in which metabolomic approach was used in some
      allergic (asthma, atopic dermatitis) and rheumatic diseases (rheumatoid
      arthritis, systemic lupus erythematosus) to explore the feasibility of this
      technique as a novel diagnostic tool in these complex disorders. 

PMID- 24744272
TI  - Periprocedural stroke and bleeding complications in patients undergoing catheter
      ablation of atrial fibrillation with different anticoagulation management:
      results from the Role of Coumadin in Preventing Thromboembolism in Atrial
      Fibrillation (AF) Patients Undergoing Catheter Ablation (COMPARE) randomized
      trial.
AB  - BACKGROUND: Periprocedural thromboembolic and hemorrhagic events are worrisome
      complications of catheter ablation for atrial fibrillation (AF). The
      periprocedural anticoagulation management could play a role in the incidence of
      these complications. Although ablation procedures performed without warfarin
      discontinuation seem to be associated with lower thromboembolic risk, no
      randomized study exists. METHODS AND RESULTS: This was a prospective, open-label,
      randomized, parallel-group, multicenter study assessing the role of continuous
      warfarin therapy in preventing periprocedural thromboembolic and hemorrhagic
      events after radiofrequency catheter ablation. Patients with CHADS2 score >=1
      were included. Patients were randomly assigned in a 1:1 ratio to the off-warfarin
      or on-warfarin arm. The incidence of thromboembolic events in the 48 hours after
      ablation was the primary end point of the study. The study enrolled 1584
      patients: 790 assigned to discontinue warfarin (group 1) and 794 assigned to
      continuous warfarin (group 2). No statistical difference in baseline
      characteristics was observed. There were 39 thromboembolic events (3.7% strokes
      [n=29] and 1.3% transient ischemic attacks [n=10]) in group 1: two events (0.87%)
      in patients with paroxysmal AF, 4 (2.3%) in patients with persistent AF, and 33
      (8.5%) in patients with long-standing persistent AF. Only 2 strokes (0.25%) in
      patients with long-standing persistent AF were observed in group 2 (P<0.001).
      Warfarin discontinuation emerged as a strong predictor of periprocedural
      thromboembolism (odds ratio, 13; 95% confidence interval, 3.1-55.6; P<0.001).
      CONCLUSION: This is the first randomized study showing that performing catheter
      ablation of AF without warfarin discontinuation reduces the occurrence of
      periprocedural stroke and minor bleeding complications compared with bridging
      with low-molecular-weight heparin. CLINICAL TRIAL REGISTRATION URL:
      http://www.clinicaltrials.gov. Unique identifier: NCT01006876.

PMID- 24744273
TI  - Medical decision making and the counting of uncertainty.

PMID- 24744274
TI  - Patient-accessible tool for shared decision making in cardiovascular primary
      prevention: balancing longevity benefits against medication disutility.
AB  - BACKGROUND: Primary prevention guidelines focus on risk, often assuming
      negligible aversion to medication, yet most patients discontinue primary
      prevention statins within 3 years. We quantify real-world distribution of
      medication disutility and separately calculate the average utilities for a range
      of risk strata. METHOD AND RESULTS: We randomly sampled 360 members of the
      general public in London. Medication aversion was quantified as the gain in
      lifespan required by each individual to offset the inconvenience (disutility) of
      taking an idealized daily preventative tablet. In parallel, we constructed tables
      of expected gain in lifespan (utility) from initiating statin therapy for each
      age group, sex, and cardiovascular risk profile in the population. This allowed
      comparison of the widths of the distributions of medication disutility and of
      group-average expectation of longevity gain. Observed medication disutility
      ranged from 1 day to >10 years of life being required by subjects (median, 6
      months; interquartile range, 1-36 months) to make daily preventative therapy
      worthwhile. Average expected longevity benefit from statins at ages >=50 years
      ranges from 3.6 months (low-risk women) to 24.3 months (high-risk men).
      CONCLUSION: We can no longer assume that medication disutility is almost zero.
      Over one-quarter of subjects had disutility exceeding the group-average longevity
      gain from statins expected even for the highest-risk (ie, highest-gain) group.
      Future primary prevention studies might explore medication disutility in larger
      populations. Patients may differ more in disutility than in prospectively
      definable utility (which provides only group-average estimates). Consultations
      could be enriched by assessing disutility and exploring its reasons.

PMID- 24744276
TI  - Function of natural internal mammary-to-coronary artery bypasses and its effect
      on myocardial ischemia.
AB  - BACKGROUND: The function of naturally existing internal mammary (IMA)-to-coronary
      artery bypasses and their quantitative effect on myocardial ischemia are unknown.
      METHODS AND RESULTS: The primary end point of this study was collateral flow
      index (CFI) obtained during two 1-minute coronary artery balloon occlusions, the
      first with and the second without simultaneous distal IMA occlusion. The
      secondary study end point was the quantitatively determined intracoronary ECG ST
      segment elevation. CFI is the ratio of simultaneously recorded mean coronary
      occlusive pressure divided by mean aortic pressure both subtracted by mean
      central venous pressure. A total of 180 pairs of CFI measurements were performed
      among 120 patients. With and without IMA occlusion, CFI was 0.110+/-0.074 and
      0.096+/-0.072, respectively (P<0.0001). The difference of CFI obtained in the
      presence minus CFI obtained in the absence of IMA occlusion was highest and most
      consistently positive during left IMA with left anterior descending artery
      occlusion and during right IMA with right coronary artery occlusion (ipsilateral
      occlusions): 0.033+/-0.044 and 0.025+/-0.027, respectively. This CFI difference
      was absent during right IMA with left anterior descending artery occlusion and
      during left IMA with right coronary artery occlusion (contralateral occlusions): 
      0.007+/-0.034 and 0.001+/-0.023, respectively (P=0.0002 versus ipsilateral
      occlusions). The respective CFI differences during either IMA with left
      circumflex artery occlusion were inconsistently positive. Intracoronary ECG ST
      segment elevations were significantly reduced during ipsilateral IMA occlusions
      but not during contralateral or left circumflex artery occlusions. CONCLUSION:
      There is a functional, ischemia-reducing extracardiac coronary artery supply via
      ipsilateral but not via contralateral natural IMA bypasses. CLINICAL TRIAL
      REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCTO1676207.

PMID- 24744275
TI  - Surgical revascularization is associated with maximal survival in patients with
      ischemic mitral regurgitation: a 20-year experience.
AB  - BACKGROUND: The optimal treatment for ischemic mitral regurgitation remains
      actively debated. Our objective was to evaluate the relationship between ischemic
      mitral regurgitation treatment strategy and survival. METHODS AND RESULTS: We
      retrospectively reviewed patients at our institution diagnosed with significant
      coronary artery disease and moderate or severe ischemic mitral regurgitation from
      1990 to 2009, categorized by medical treatment alone, percutaneous coronary
      intervention, coronary artery bypass grafting (CABG), or CABG plus mitral valve
      repair or replacement. Kaplan-Meier methods and multivariable Cox proportional
      hazards analyses were performed to assess the relationship between treatment
      strategy and survival, with the use of propensity scores to account for nonrandom
      treatment assignment. A total of 4989 patients were included: medical treatment
      alone=36%, percutaneous coronary intervention=26%, CABG=33%, and CABG plus mitral
      valve repair or replacement=5%. Median follow-up was 5.37 years. Compared with
      medical treatment alone, significantly lower mortality was observed in patients
      treated with percutaneous coronary intervention (adjusted hazard ratio, 0.83; 95%
      confidence interval, 0.76-0.92; P=0.0002), CABG (adjusted hazard ratio, 0.56; 95%
      confidence interval, 0.51-0.62; P<0.0001), and CABG plus mitral valve repair or
      replacement (adjusted hazard ratio, 0.69; 95% confidence interval, 0.57-0.82;
      P<0.0001). There was no significant difference in these results based on mitral
      regurgitation severity. CONCLUSIONS: Patients with significant coronary artery
      disease and moderate or severe ischemic mitral regurgitation undergoing CABG
      alone demonstrated the lowest risk of death. CABG with or without mitral valve
      surgery was associated with lower mortality than either percutaneous coronary
      intervention or medical treatment alone.

PMID- 24744277
TI  - Transfer of patients with ST-elevation myocardial infarction for primary
      percutaneous coronary intervention: a province-wide evaluation of "door-in to
      door-out" delays at the first hospital.
AB  - BACKGROUND: Interhospital transfer of patients with ST-elevation myocardial
      infarction (STEMI) for primary percutaneous coronary intervention (PPCI) is
      associated with longer delays to reperfusion, related in part to turnaround
      ("door in" to "door out," or DIDO) time at the initial hospital. As part of a
      systematic, province-wide evaluation of STEMI care, we examined DIDO times and
      associations with patient, hospital, and process-of-care factors. METHODS AND
      RESULTS: We performed medical chart review for STEMI patients transferred for
      PPCI during a 6-month period (October 1, 2008, through March 31, 2009) and linked
      these data to ambulance service databases. Two core laboratory cardiologists
      reviewed presenting ECGs to identify left bundle-branch block and, in the absence
      of left bundle-branch block, definite STEMI (according to both cardiologists) or
      an ambiguous reading. Median DIDO time was 51 minutes (25th to 75th percentile:
      35-82 minutes); 14.1% of the 988 patients had a timely DIDO interval (<=30
      minutes as recommended by guidelines). The data-to-decision delay was the major
      contributor to DIDO time. Female sex, more comorbidities, longer symptom
      duration, arrival by means other than ambulance, arrival at a hospital not
      exclusively transferring for PPCI, arrival at a center with a low STEMI volume,
      and an ambiguous ECG were independently associated with longer DIDO time. When
      turnaround was timely, 70% of patients received timely PPCI (door-to-device time
      <=90 minutes) versus 14% if turnaround was not timely (P<0.0001). CONCLUSIONS:
      Benchmark DIDO times for STEMI patients transferred for PPCI were rarely
      achieved. Interventions aimed at facilitating the transfer decision, particularly
      in cases of ECGs that are difficult to interpret, are likely to have the best
      impact on reducing delay to reperfusion.

PMID- 24744278
TI  - PACS administrators' and radiologists' perspective on the importance of features
      for PACS selection.
AB  - Picture archiving and communication systems (PACS) play a critical role in
      radiology. This paper presents the criteria important to PACS administrators for
      selecting a PACS. A set of criteria are identified and organized into an
      integrative hierarchical framework. Survey responses from 48 administrators are
      used to identify the relative weights of these criteria through an analytical
      hierarchy process. The five main dimensions for PACS selection in order of
      importance are system continuity and functionality, system performance and
      architecture, user interface for workflow management, user interface for image
      manipulation, and display quality. Among the subdimensions, the highest weights
      were assessed for security, backup, and continuity; tools for continuous
      performance monitoring; support for multispecialty images; and voice
      recognition/transcription. PACS administrators' preferences were generally in
      line with that of previously reported results for radiologists. Both groups
      assigned the highest priority to ensuring business continuity and preventing loss
      of data through features such as security, backup, downtime prevention, and tools
      for continuous PACS performance monitoring. PACS administrators' next high
      priorities were support for multispecialty images, image retrieval speeds from
      short-term and long-term storage, real-time monitoring, and architectural issues
      of compatibility and integration with other products. Thus, next to ensuring
      business continuity, administrators' focus was on issues that impact their
      ability to deliver services and support. On the other hand, radiologists gave
      high priorities to voice recognition, transcription, and reporting; structured
      reporting; and convenience and responsiveness in manipulation of images. Thus,
      radiologists' focus appears to be on issues that may impact their productivity,
      effort, and accuracy. 

PMID- 24744279
TI  - Stress hormones in relation to breeding status and territory location in colonial
      king penguin: a role for social density?
AB  - Because glucocorticoid (stress) hormones fundamentally affect various aspects of
      the behaviour, life history and fitness of free-living vertebrates, there is a
      need to understand the environmental factors shaping their variation in natural
      populations. Here, we examined whether spatial heterogeneity in breeding
      territory quality affected the stress of colonial king penguin (Aptenodytes
      patagonicus). We assessed the effects of local climate (wind, sun and ambient
      temperature) and social conditions (number of neighbours, distance to neighbours)
      on the baseline levels of plasma total corticosterone (CORT) in 77 incubating and
      42 chick-brooding birds, breeding on territories of central or peripheral colony
      location. We also assessed the oxidative stress status of a sub-sample of central
      vs. peripheral chick-brooders to determine whether chronic stress arose from
      breeding on specific territories. On average, we found that brooders had 55%
      higher CORT levels than incubators. Regardless of breeding status, central birds
      experienced greater social density (higher number of neighbours, shorter distance
      between territories) and had higher CORT levels than peripheral birds. Increasing
      social density positively explained 40% of the variation in CORT levels of both
      incubators and brooders, but the effect was more pronounced in brooders. In
      contrast, climate was similar among breeding territories and did not
      significantly affect the CORT levels of breeding birds. In brooders, oxidative
      stress status was not affected by local density or weather conditions. These
      results highlight that local heterogeneity in breeding (including social)
      conditions may strongly affect the stress levels of breeding seabirds. The
      fitness consequences of such variation remain to be investigated.

PMID- 24744280
TI  - A real-time electronic alert to improve detection of acute kidney injury in a
      large teaching hospital.
AB  - BACKGROUND: Acute kidney injury (AKI) is a common and serious problem in
      hospitalized patients. Early detection is critical for optimal management but in
      practice is currently inadequate. To improve outcomes in AKI, development of
      early detection tools is essential. METHODS: We developed an automated real-time
      electronic alert system employing algorithms which combined internationally
      recognized criteria for AKI [Risk, Injury, Failure, Loss, End-stage kidney
      disease (RIFLE) and Acute Kidney Injury Network (AKIN)]. All adult patients
      admitted to Nottingham University Hospitals were included. Where a patient's
      serum creatinine increased sufficiently to define AKI, an electronic alert was
      issued, with referral to an intranet-based AKI guideline. Incidence of AKI Stages
      1-3, in-hospital mortality, length of stay and distribution between specialties
      is reported. RESULTS: Between May 2011 and April 2013, 59,921 alerts resulted
      from 22,754 admission episodes, associated with 15,550 different patients.
      Overall incidence of AKI for inpatients was 10.7%. Highest AKI stage reached was:
      Stage 1 in 7.2%, Stage 2 in 2.2% and Stage 3 in 1.3%. In-hospital mortality for
      all AKI stages was 18.5% and increased with AKI stage (12.5, 28.4, 35.7% for
      Stages 1, 2 and 3 AKI, respectively). Median length of stay was 9 days for all
      AKI. CONCLUSIONS: This is the first fully automated real time AKI e-alert system,
      using AKIN and RIFLE criteria, to be introduced to a large National Health
      Service hospital. It has provided one of the biggest single-centre AKI datasets
      in the UK revealing mortality rates which increase with AKI stage. It is likely
      to have improved detection and management of AKI. The methodology is transferable
      to other acute hospitals.

PMID- 24744282
TI  - Treatment of atherosclerotic renovascular hypertension: review of observational
      studies and a meta-analysis of randomized clinical trials.
AB  - Atherosclerotic renal artery stenosis can cause ischaemic nephropathy and
      arterial hypertension. We herein review the observational and randomized clinical
      trials (RCTs) comparing medical and endovascular treatment for control of
      hypertension and renal function preservation. Using the Population Intervention
      Comparison Outcome (PICO) strategy, we identified the relevant studies and
      performed a novel meta-analysis of all RCTs to determine the efficacy and safety
      of endovascular treatment when compared with medical therapy. The following
      outcomes were examined: baseline follow-up difference in mean systolic and
      diastolic blood pressure (BP), serum creatinine, number of drugs at follow-up,
      incident events (heart failure, stroke, and worsening renal function), mortality,
      cumulative relative risk of heart failure, stroke, and worsening renal function.
      Seven studies comprising a total of 2155 patients (1741 available at follow-up)
      were considered, including the recently reported CORAL Study. Compared with
      baseline, diastolic BP fell more at follow-up in patients in the endovascular
      than in the medical treatment arm (standard difference in means -0.21, 95%
      confidence interval (CI): -0.342 to -0.078, P = 0.002) despite a greater
      reduction in the mean number of antihypertensive drugs (standard difference in
      means -0.201, 95% CI: -0.302 to -0.1, P < 0.001). At variance, follow-up changes
      (from baseline) of systolic BP, serum creatinine, and incident cardiovascular
      event rates did not differ between treatment arms. Thus, patients with
      atherosclerotic renal artery stenosis receiving endovascular treatment required
      less anti-antihypertensive drugs at follow-up than those medically treated.
      Notwithstanding this, they evidenced a better control of diastolic BP. 

PMID- 24744281
TI  - Acute kidney injury in Latin America: a view on renal replacement therapy
      resources.
AB  - BACKGROUND: Acute kidney injury (AKI) has increasingly been recognized as an
      important public health issue due to its rising frequency, its associations with
      early and late adverse outcomes and its economic burden. METHODS: Given the
      importance of determining the available resources to address this serious issue,
      the AKI Committee of SLANH conducted a survey to obtain information about
      infrastructure, human resources and equipment devoted to the treatment of AKI in
      Latin America RESULTS: A total of 246 units from 14 countries participated in the
      survey, the majority of them pertaining to nephrology divisions in teaching
      hospitals. Intermittent hemodialysis was universally performed by all of the
      units, and less frequently, slow extended dialysis (40%) and continuous renal
      replacement therapy (23%) were performed. Seventy-nine units (30%) perform
      peritoneal dialysis, but only 51 (19%) of them reported having treated at least 1
      patient with this technique in the last 3 months pre-survey. The vast majority of
      the units reported adequate water treatment and use of modern filter membranes.
      Most of the patients received renal replacement therapy (RRT) in the intensive
      care unit. Specific causes of AKI were reported in different frequencies, with a
      heterogeneous pattern among the countries. Septic abortion, hemolytic-uremic
      syndrome, community-acquired diarrhea and leptospirosis were the etiologies most
      frequently associated with AKI. CONCLUSIONS: To our knowledge, this report was
      the first available study of the equipment and human resources utilized for RRT
      in AKI patients in Latin America.

PMID- 24744284
TI  - Defra seeks views on proposals for statutory TB testing of camelids.

PMID- 24744286
TI  - Wales reports on progress with badger vaccination.

PMID- 24744283
TI  - Obesity-associated Gingival Vascular Inflammation and Insulin Resistance.
AB  - Obesity is a risk factor for periodontitis, but the pathogenic mechanism involved
      is unclear. We studied the effects of insulin in periodontal tissues during the
      state of obesity-induced insulin resistance. Gingival samples were collected from
      fatty (ZF) and lean (ZL, control) Zucker rats. Endothelial nitric oxide synthase
      (eNOS) expression was decreased, and activities of protein kinase C (PKC) alpha,
      beta2, delta, and epsilon isoforms were significantly increased in the gingiva
      from ZF rats compared with those from ZL rats. Expression of oxidative stress
      markers (mRNA) and the p65 subunit of NF-kappaB was significantly increased in ZF
      rats. Immunohistochemistry revealed that NF-kappaB activation was also increased
      in the gingival endothelial cells from transgenic mice overexpressing NF-kappaB
      dependent enhanced green fluorescent protein (GFP) and on a high-fat vs. normal
      chow diet. Analysis of the gingiva showed that insulin-induced phosphorylation of
      IRS-1, Akt, and eNOS was significantly decreased in ZF rats, but Erk1/2
      activation was not affected. General PKC inhibitor and an anti-oxidant normalized
      the action of insulin on Akt and eNOS activation in the gingiva from ZF rats.
      This provided the first documentation of obesity-induced insulin resistance in
      the gingiva. Analysis of our data suggested that PKC activation and oxidative
      stress may selectively inhibit insulin-induced Akt and eNOS activation, causing
      endothelial dysfunction and inflammation. 

PMID- 24744287
TI  - BVA support for campaign to keep dogs on leads near livestock.

PMID- 24744288
TI  - 'What's good for the consumer is good for the profession'.
AB  - The way the RCVS handles complaints is undergoing 'a refresh and revolution'
      which, it believes, will bring benefits to both clients and veterinary surgeons.
      At the recent BSAVA congress, the College's chief executive and its Registrar
      explained how things are changing. Kathryn Clark reports. 

PMID- 24744290
TI  - Pet travel, passports and potential problems.
AB  - The movement - both legal and illegal - of pet animals, particularly dogs, was
      discussed in a series of 'big issues' debates at this year's BSAVA congress.
      Laura Honey reports. 

PMID- 24744293
TI  - A One Health approach to the control of zoonotic vectorborne pathogens.
AB  - In the fourth article in Veterinary Record's series of articles promoting One
      Health, Chris Oura discusses the threats posed to both animal and human
      populations by vectorborne diseases and how a multidisciplinary approach would be
      effective in reducing the risks and managing outbreaks. 

PMID- 24744294
TI  - Predict and prevent versus test and treat.

PMID- 24744295
TI  - RHDV variant 2 presence detected in Scotland.

PMID- 24744296
TI  - History of One Health and One Medicine.

PMID- 24744297
TI  - Milk withdrawal periods in dairy cows.

PMID- 24744298
TI  - VBF board election.

PMID- 24744299
TI  - DNA analysis for juvenile kidney disease in boxers.

PMID- 24744301
TI  - Nuclear receptor 4 group A member 1 determines hepatitis C virus entry efficiency
      through the regulation of cellular receptor and apolipoprotein E expression.
AB  - Orphan nuclear receptor subfamily 4 group A member 1 (NR4A1) is a transcription
      factor stimulated by many factors and plays pivotal roles in metabolism,
      proliferation and apoptosis. In this study, the expression of NR4A1 in Huh7.5.1
      cells was significantly upregulated by hepatitis C virus (HCV) infection. The
      silencing of NR4A1 inhibited the entry of HCV and reduced the specific
      infectivity of secreted HCV particles but had only minor or no effect on the
      genome replication and translation, virion assembly and virus release steps of
      the virus life cycle. Further experiments demonstrated that the silencing of
      NR4A1 affected virus entry through pan-downregulation of the expression of HCV
      receptors scavenger receptor BI, occludin, claudin-1 and epidermal growth factor
      receptor but not CD81. The reduced specific infectivity of HCV in the knockdown
      cells was due to decreased apolipoprotein E (ApoE) expression. These results
      explain the delayed spread of HCV in NR4A1 knockdown Huh7.5.1 cells. Thus, NR4A1
      plays a role in HCV replication through regulating the expression of HCV
      receptors and ApoE, and facilitates HCV entry and spread. 

PMID- 24744300
TI  - Identification of novel anelloviruses with broad diversity in UK rodents.
AB  - Anelloviruses are a family of small circular ssDNA viruses with a vast genetic
      diversity. Human infections with the prototype anellovirus, torque teno virus
      (TTV), are ubiquitous and related viruses have been described in a number of
      other mammalian hosts. Despite over 15 years of investigation, there is still
      little known about the pathogenesis and possible disease associations of
      anellovirus infections, arising in part due to the lack of a robust cell culture
      system for viral replication or tractable small-animal model. We report the
      identification of diverse anelloviruses in several species of wild rodents. The
      viruses are highly prevalent in wood mice (Apodemus sylvaticus) and field voles
      (Microtus agrestis), detectable at a low frequency in bank voles (Myodes
      glareolus), but absent from house mice (Mus musculus). The viruses identified
      have a genomic organization consistent with other anelloviruses, but form two
      clear phylogenetic groups that are as distinct from each other as from defined
      genera. 

PMID- 24744302
TI  - The risk of seizures among the carbapenems: a meta-analysis.
AB  - OBJECTIVES: A consensus exists among clinicians that imipenem/cilastatin is the
      most epileptogenic carbapenem, despite inconsistencies in the literature.
      METHODS: We conducted a meta-analysis of all randomized controlled trials
      comparing carbapenems with each other or with non-carbapenem antibiotics to
      assess the risk of seizures for imipenem, meropenem, ertapenem and doripenem.
      RESULTS: In the risk difference (RD) analysis, there were increased patients with
      seizure (2 per 1000 persons, 95% CI 0.001, 0.004) among recipients of carbapenems
      versus non-carbapenem antibiotics. This difference was largely attributed to
      imipenem as its use was associated with an additional 4 patients per 1000 with
      seizure (95% CI 0.002, 0.007) compared with non-carbapenem antibiotics, whereas
      none of the other carbapenems was associated with increased seizure. Similarly,
      in the pooled OR analysis, carbapenems were associated with a significant
      increase in the risk of seizures relative to non-carbapenem comparator
      antibiotics (OR 1.87, 95% CI 1.35, 2.59). The ORs for risk of seizures from
      imipenem, meropenem, ertapenem and doripenem compared with other antibiotics were
      3.50 (95% CI 2.23, 5.49), 1.04 (95% CI 0.61, 1.77), 1.32 (95% CI 0.22, 7.74) and
      0.44 (95% CI 0.13, 1.53), respectively. In studies directly comparing imipenem
      and meropenem, there was no difference in epileptogenicity in either RD or pooled
      OR analyses. CONCLUSIONS: The absolute risk of seizures with carbapenems was low,
      albeit higher than with non-carbapenem antibiotics. Although imipenem was more
      epileptogenic than non-carbapenem antibiotics, there was no statistically
      significant difference in the imipenem versus meropenem head-to-head comparison.

PMID- 24744303
TI  - Glycopeptide use is associated with increased mortality in Enterococcus faecalis
      bacteraemia.
AB  - OBJECTIVES: Enterococci are an important cause of nosocomial and community
      acquired infections, with bacteraemia being one of the most common presentations.
      Although inappropriate antimicrobial therapy has been associated with poorer
      outcomes in Enterococcus faecalis (EF) bacteraemia, the impact of antimicrobial
      choice, namely beta-lactam versus glycopeptide therapy, has not been well
      described. We sought to determine whether choice of antibiotic affects patient
      outcomes in EF bacteraemia. PATIENTS AND METHODS: This retrospective cohort study
      was conducted at Liverpool and Bankstown Lidcombe Hospitals, Sydney, Australia
      between 2006 and 2013. Medical records and laboratory data for consecutive EF
      bacteraemias were reviewed. Clinical and microbiological data were obtained for
      all patients who received appropriate antimicrobial therapy with either a beta
      lactam or a glycopeptide antibiotic. Outcomes and predictors of mortality were
      determined and treatment groups were compared. RESULTS: One hundred and seventy
      two episodes of clinically significant EF bacteraemias received appropriate
      antimicrobial therapy with a beta-lactam (n = 126) or a glycopeptide (n = 46).
      All-cause 30 day mortality was 15.1%, with mortality significantly higher in
      patients receiving glycopeptide therapy compared with beta-lactam therapy (26.1%
      versus 11.1%, P = 0.015). Glycopeptide therapy remained an independent predictor
      of 30 day mortality [OR 2.46 (95% CI 1.01-6.02), P = 0.048]. APACHE II score [OR
      1.10 (95% CI 1.02-1.18), P = 0.011] and malignancy [OR 2.58 (95% CI 1.03-6.49), P
      = 0.044] were also independent predictors of 30 day mortality. CONCLUSIONS:
      Glycopeptide use is associated with increased mortality in patients with EF
      bacteraemia. In the treatment of beta-lactam-susceptible EF bacteraemia, beta
      lactams should be considered first-line therapy.

PMID- 24744304
TI  - Variations in the sales and sales patterns of veterinary antimicrobial agents in
      25 European countries.
AB  - OBJECTIVES: To describe sales and sales patterns of veterinary antimicrobial
      agents in 25 European Union (EU)/European Economic Area (EEA) countries for 2011.
      METHODS: Data on the sales of veterinary antimicrobial agents from 25 EU member
      states and EEA countries for 2011 were collected at package level (name,
      formulation, strength, pack size, number of packages sold) according to a
      standardized protocol and template and presented in a harmonized manner. These
      data were calculated to express amounts sold, in metric tonnes, of active
      ingredient of each package. A population correction unit (PCU) was applied as a
      proxy for the animal biomass potentially treated with antimicrobial agents. The
      indicator used to express sales was milligrams of active substance per PCU.
      RESULTS: Substantial variations in the sales patterns and in the magnitude of
      sales of veterinary antimicrobial agents, expressed as mg/PCU, between the
      countries were observed. The proportion of sales, in mg/PCU, of products
      applicable for treatment of groups or herds of animals (premixes, oral powders
      and oral solution) varied considerably between the countries. CONCLUSIONS: Some
      countries reported much lower sales of veterinary antimicrobial agents than
      others, when expressed as mg/PCU. Sales patterns varied between countries,
      particularly with respect to pharmaceutical forms. Further studies are needed to
      understand the factors that explain the observed differences.

PMID- 24744305
TI  - Pharmacogenetics of drug metabolizing enzymes in Brazilian populations.
AB  - Phase I and II drug metabolizing enzymes (DMEs) play an important role in
      biotransformation of endogenous and exogenous compounds including drugs currently
      used in pharmacoterapy. Moreover, the genetic variability of DMEs causes
      important interindividual differences in drug and metabolite exposure, drug
      response, and risk of adverse drug reactions. We reviewed
      pharmacogenetics/pharmacogenomics (PGx) studies that evaluated the influence of
      polymorphisms in the CYPs genes - mainly CYP1, CYP2 and CYP3 gene families - and
      in the phase II genes - TPMT, NAT2, GSTs and UGTs - on therapeutic response in
      Brazilian cohorts. Ethnic admixture of Brazilians resulted in a population
      characterized by a unique genetic profile, in which ancestry informative markers
      change continuously among ethnic groups. Therefore, some of the PGx biomarkers
      have a different distribution among Brazilians and PGx data from well-defined
      ethnic groups are not applicable to Brazilian populations. PGx data focused on
      phase I and phase II DMEs from Brazilian studies are needed in order to establish
      the influence of the genetic diversity on therapeutic response to clinically
      relevant drugs in a population with a composition from a complex genetic
      admixture. These studies and their impact are discussed in this review.

PMID- 24744306
TI  - Dietary carotenoids are associated with cardiovascular disease risk biomarkers
      mediated by serum carotenoid concentrations.
AB  - Hyperlipidemia and elevated circulating C-reactive protein (CRP) and total
      homocysteine (tHcy) concentrations are cardiovascular disease (CVD) risk factors.
      Previous studies indicated that higher serum carotenoid concentrations were
      inversely associated with some of these biomarkers. However, whether dietary
      carotenoid intake is inversely associated with these CVD risk biomarkers is not
      well known. We assessed the associations between individual dietary carotenoid
      intake and CVD risk biomarkers and tested whether the serum carotenoid
      concentrations explain (mediate) or influence the strength of (moderate) the
      associations, if any association exists. Dietary data collected from 2 24-h
      dietary recalls and serum measurements in adult men (n = 1312) and women (n =
      1544) from the NHANES 2003-2006 were used. Regression models designed for survey
      analysis were used to examine the associations between individual dietary
      carotenoids and log-transformed blood cholesterol, CRP, and tHcy. The
      corresponding individual serum carotenoid concentration was considered as
      mediator (and moderator if applicable). After adjustment for covariates,
      significant inverse associations with LDL cholesterol were observed for dietary
      beta-carotene (P < 0.05) and lutein + zeaxanthin (P < 0.001), and with tHcy for
      dietary beta-carotene (P < 0.05), lycopene (P < 0.05), and total carotenoids (P <
      0.05). Dietary lutein + zeaxanthin intake was also positively associated with HDL
      cholesterol concentrations (P < 0.01). Most of these associations were null after
      additional adjustment for corresponding serum carotenoid concentrations,
      indicating the complete mediation effects of serum carotenoids. Serum beta
      carotene significantly moderated the associations between dietary beta-carotene
      and CRP (P-interaction < 0.05), and quartile 4 of dietary beta-carotene was
      associated with lower CRP concentrations only among participants with serum beta
      carotene > 0.43 MUmol/L. In this population-based cross-sectional study, serum
      carotenoids were mediators of dietary carotenoids and CVD risk biomarker
      associations. Serum beta-carotene was also a moderator of the dietary beta
      carotene and CRP association. These findings may help in the design of future
      intervention studies on dietary carotenoids in the prevention of CVD. 

PMID- 24744307
TI  - High fish plus fish oil intake is associated with slightly reduced risk of venous
      thromboembolism: the Tromso Study.
AB  - Current knowledge of the effect of fish consumption on risk of venous
      thromboembolism (VTE) is scarce and diverging. Therefore, the purpose of the
      present study was to investigate the impact of fish consumption and fish oil
      supplements on the risk of VTE in a population-based cohort. Weekly intake of
      fish for dinner and intake of fish oil supplements during the previous year were
      registered in 23,621 persons aged 25-97 y who participated in the Tromso Study
      from 1994 to 1995. Incident VTE events were registered throughout follow-up (31
      December 2010). Cox-regression models were used to calculate HRs for VTE,
      adjusted for age, body mass index, sex, triglycerides, HDL cholesterol, physical
      activity, and education level. During a median of 15.8 y of follow-up there were
      536 incident VTE events. High fish consumption was associated with a slightly
      reduced risk of VTE. Participants who ate fish >=3 times/wk had 22% lower risk of
      VTE than those who consumed fish 1-1.9 times/wk (multivariable HR: 0.78; 95% CI:
      0.60, 1.01; P = 0.06). The addition of fish oil supplements strengthened the
      inverse association with risk of VTE. Participants who consumed fish >=3 times/wk
      who additionally used fish oil supplements had 48% lower risk than those who
      consumed fish 1-1.9 times/wk but did not use fish oil supplements (HR: 0.52; 95%
      CI: 0.34, 0.79; P = 0.002). In conclusion, a high weekly intake (>=3 times/wk) of
      fish was associated with a slightly reduced risk of VTE, and the addition of fish
      oil supplements strengthened the inverse effect. 

PMID- 24744308
TI  - Healthy dietary habits score as an indicator of diet quality in New Zealand
      adolescents.
AB  - Adoption of optimal dietary habits during adolescence is associated with better
      health outcomes later in life. However, the associations between a pattern of
      healthy dietary habits encapsulated in an index and sociodemographic and nutrient
      intake have not been examined among adolescents. This study aimed to develop a
      behavior-based diet index and examine its validity in relation to
      sociodemographic factors, nutrient intakes, and biomarkers in a representative
      sample of New Zealand (NZ) adolescents aged 15-18 y (n = 694). A 17-item Healthy
      Dietary Habits Score for Adolescents (HDHS-A) was developed based on dietary
      habits information from the 2008/2009 NZ Adult Nutrition Survey. Post hoc trend
      analyses were used to identify the associations between HDHS-A score and nutrient
      intakes estimated by single 24-h diet recalls and selected nutritional
      biomarkers. Being female, not of Maori or Pacific ethnicity, and living in the
      least-deprived socioeconomic quintile were associated with a higher HDHS-A score
      (all P < 0.001). HDHS-A tertile was associated positively with intake of protein,
      dietary fiber, polyunsaturated fatty acid, and lactose and negatively with
      sucrose. Associations in the expected directions were also found with most
      micronutrients (P < 0.05), urinary sodium (P < 0.001), whole blood (P < 0.05),
      serum (P < 0.01), and RBC folate (P < 0.05) concentrations. This suggests that
      the HDHS-A is a valid indicator of diet quality among NZ adolescents. 

PMID- 24744310
TI  - Protein-centric meals for optimal protein utilization: can it be that simple?

PMID- 24744309
TI  - Dietary intake of advanced glycation end products did not affect endothelial
      function and inflammation in healthy adults in a randomized controlled trial.
AB  - When food is heated to high temperatures, the characteristic "browning" generates
      advanced glycation end products (AGEs). AGEs are associated with an increased
      risk of cardiovascular disease, diabetes, and other adverse outcomes. Whether
      dietary AGEs are absorbed and are harmful to human health remains highly
      controversial. The objective of this study was to compare the effects of a diet
      high or low in AGEs on endothelial function, circulating AGEs, inflammatory
      mediators, and circulating receptors for AGEs in healthy adults. A randomized,
      parallel-arm, controlled dietary intervention was conducted for 6 wk with 24
      healthy adults, aged 50-69 y, that compared isocaloric, food-equivalent diets
      that were prepared at either high or mild temperatures. Peripheral arterial
      tonometry, serum and urine carboxymethyl-lysine (CML), inflammatory mediators
      (interleukin-6, C-reactive protein, vascular adhesion molecule-1, and tumor
      necrosis factor-alpha receptors I and II), soluble receptor for AGEs, and
      endogenous secretory receptor for AGEs were measured at baseline and after 6 wk
      of dietary intervention. In the low-AGE diet group, the following changed from
      baseline to 6 wk (mean +/- SE): serum CML from 763 +/- 24 to 679 +/- 29 ng/mL (P
      = 0.03) and urine CML from 1.37 +/- 1.47 to 0.77 +/- 2.01 MUg/mL creatinine (P =
      0.02). There were no significant changes in serum and urinary CML concentrations
      from baseline to follow-up in the high-AGE diet group. A high- or low-AGE diet
      had no significant impact on peripheral arterial tonometry or any inflammatory
      mediators after 6 wk of dietary intervention. In healthy middle-aged to older
      adults, consumption of a diet high or low in AGEs for 6 wk had no impact on
      endothelial function and inflammatory mediators, 2 precursors of cardiovascular
      disease.

PMID- 24744311
TI  - Caloric beverages were major sources of energy among children and adults in
      Mexico, 1999-2012.
AB  - Mexico, with 1 of the highest obesity prevalences in the world, instituted a 10%
      excise tax for any sugar-sweetened beverage (SSB) starting on 1 January 2014.
      Understanding the recent patterns and trends in beverage intake and sales in
      Mexico provides both background and baseline data for the importance of SSBs and
      other beverages in the Mexican diet. We analyzed a single 24-h dietary recall
      from 2 nationally representative surveys: the Mexican Nutrition Survey 1999 (n =
      6049) and the National Health and Nutrition Survey 2012 (n = 10,343). To describe
      trends and patterns in beverages, we calculated the volume and energy intake per
      capita and per consumer and the proportion of consumers of each beverage group in
      each survey. A commercial sales dataset was used to describe beverage sales
      trends from 1999 to 2012. From 1999 to 2012, total daily energy from beverages
      increased among children aged 5-11 y (+45.3 kcal), females aged 12-19 y (+57.3
      kcal), and adult females aged 20-49 y (+96.4 kcal) (P < 0.05). Over the same
      period, intake of beverages with added sugars increased, specifically flavored
      milk, agua fresca (fruit water made in stalls or at home, usually with added
      sugars), and fruit drinks among children aged 5-11 y and females aged 12-19 y and
      caloric coffee/tea, soda, and agua fresca among adult females aged 20-49 y. In
      2012, beverages represented 17.5% (325 kcal) and 19.0% (382 kcal) of the total
      daily energy intake per capita in children aged 1-19 y and adults aged >=20 y,
      respectively. In 2012, flavored milk beverages, caloric soda, and high-fat milk
      were the top 3 major contributors to total daily energy intake per capita in all
      children aged 1-19 y. Caloric soda, caloric coffee/tea, and agua fresca were the
      top 3 major energy contributors in adults aged >=20 y. From 1999 to 2012, sales
      of soda, fruit-flavored drinks, and flavored waters increased. In conclusion,
      consumption of several beverages with added sugars increased among children and
      adult females in Mexico. Because caloric soda is currently 1 of the top beverages
      consumed, a 10% tax on SSBs might help to significantly reduce added sugars
      intake in Mexico. 

PMID- 24744312
TI  - Dairy intakes at age 10 years do not adversely affect risk of excess adiposity at
      13 years.
AB  - Evidence of an association between milk intake and childhood adiposity remains
      inconsistent, with few data available regarding the effects of the amount of
      dairy fat consumed. This study examined the relation between dairy consumption
      (total, full, and reduced fat) at age 10 y on risk of excess adiposity at age 13
      y in participants of the Avon Longitudinal Study of Parents and Children (ALSPAC;
      n = 2455). Intakes were assessed by 3-d dietary records. Total body fat mass
      (TBFM) using dual-energy X-ray absorptiometry was examined at 13 y. Outcomes
      included excess TBFM (top quintile of TBFM), overweight, and change in body mass
      index (BMI). The highest vs. lowest quartile of total dairy consumers (g/d) at
      age 10 y did not have an increased risk of excess TBFM (OR: 0.73; 95% CI: 0.46,
      1.16; P-trend = 0.28) or overweight (OR: 0.69; 95% CI: 0.41, 1.15; P = 0.24) at
      age 13 y. Children in the highest quartile of full-fat dairy intakes vs. those in
      the lowest quartile had a reduced risk of excess TBFM (OR: 0.64; 95% CI: 0.41,
      1.00; P = 0.04) and a suggestion of a reduction in overweight (OR: 0.65; 95% CI:
      0.40, 1.06; P = 0.19) at age 13 y. Furthermore, the highest vs. lowest consumers
      of full-fat products had smaller gains in BMI during follow-up [2.5 kg/m2 (95%
      CI: 2.2, 2.7) vs. 2.8 kg/m2 (95% CI: 2.5, 3.0); P < 0.01]. Associations with
      reduced-fat dairy consumption did not attain statistical significance. In this
      study, dairy consumption was not related to excess fat accumulation during late
      childhood. Estimates had wide confidence limits but generally showed inverse
      relations between dairy intakes and risk of excess adiposity. Additional
      prospective research is warranted to confirm the effects of dairy intake on
      obesity in children.

PMID- 24744313
TI  - Gestational iron deficiency differentially alters the structure and function of
      white and gray matter brain regions of developing rats.
AB  - Gestational iron deficiency (ID) has been associated with a wide variety of
      central nervous system (CNS) impairments in developing offspring. However, a
      focus on singular regions has impeded an understanding of the CNS-wide effects of
      this micronutrient deficiency. Because the developing brain requires iron during
      specific phases of growth in a region-specific manner, we hypothesized that
      maternal iron deprivation would lead to region-specific impairments in the CNS of
      offspring. Female rats were fed an iron control (Fe+) or iron-deficient (Fe-)
      diet containing 240 or 6 MUg/g iron during gestation and lactation. The corpus
      callosum (CC), hippocampus, and cortex of the offspring were analyzed at
      postnatal day 21 (P21) and/or P40 using structural and functional measures. In
      the CC at P40, ID was associated with reduced peak amplitudes of compound action
      potentials specific to myelinated axons, in which diameters were reduced by ~20%
      compared with Fe+ controls. In the hippocampus, ID was associated with a 25%
      reduction in basal dendritic length of pyramidal neurons at P21, whereas
      branching complexity was unaffected. We also identified a shift toward increased
      proximal branching of apical dendrites in ID without an effect on overall length
      compared with Fe+ controls. ID also affected cortical neurons, but unlike the
      hippocampus, both apical and basal dendrites displayed a uniform decrease in
      branching complexity, with no significant effect on overall length. These
      deficits culminated in significantly poorer performance of P40 Fe- offspring in
      the novel object recognition task. Collectively, these results demonstrate that
      non-anemic gestational ID has a significant and region-specific impact on
      neuronal development and may provide a framework for understanding and
      recognizing the presentation of clinical symptoms of ID. 

PMID- 24744314
TI  - Micronutrient deficiencies are common in 6- to 8-year-old children of rural
      Nepal, with prevalence estimates modestly affected by inflammation.
AB  - Subclinical micronutrient deficiencies remain a hidden aspect of malnutrition for
      which comprehensive data are lacking in school-aged children. We assessed the
      micronutrient status of Nepalese children, aged 6 to 8 y, born to mothers who
      participated in a community-based antenatal micronutrient supplementation trial
      from 1999 to 2001. Of 3305 participants, plasma indicators were assessed in a
      random sample of 1000 children. Results revealed deficiencies of vitamins A
      (retinol <0.70 MUmol/L, 8.5%), D (25-hydroxyvitamin D <50 nmol/L, 17.2%), E
      (alpha-tocopherol <9.3 MUmol/L, 17.9%), K (decarboxy prothombin >2 MUg/L, 20%), B
      12 (cobalamin <150 pmol/L, 18.1%), B-6 [pyridoxal-5'-phosphate (PLP) <20 nmol/L,
      43.1%], and beta-carotene (41.5% <0.09 MUmol/L), with little folate deficiency
      (6.2% <13.6 nmol/L). Deficiencies of iron [ferritin <15 MUg/L, 10.7%; transferrin
      receptor (TfR) >8.3 mg/L, 40.1%; TfR:ferritin >500 MUg/MUg, 14.3%], iodine
      (thyroglobulin >40 MUg/L, 11.4%), and selenium (plasma selenium <0.89 MUmol/L,
      59.0%) were observed, whereas copper deficiency was nearly absent (plasma copper
      <11.8 MUmol/L, 0.7%). Hemoglobin was not assessed. Among all children, 91.7%
      experienced at least 1 micronutrient deficiency, and 64.7% experienced multiple
      deficiencies. Inflammation (alpha-1 acid glycoprotein >1 g/L, C-reactive protein
      >5 mg/L, or both) was present in 31.6% of children, affecting the prevalence of
      deficiency as assessed by retinol, beta-carotene, PLP, ferritin, TfR, selenium,
      copper, or having any or multiple deficiencies. For any nutrient, population
      deficiency prevalence estimates were altered by <=5.4% by the presence of
      inflammation, suggesting that the majority of deficiencies exist regardless of
      inflammation. Multiple micronutrient deficiencies coexist in school-aged children
      in rural Nepal, meriting more comprehensive strategies for their assessment and
      prevention. 

PMID- 24744316
TI  - The metabolizable energy of dietary resistant maltodextrin is variable and alters
      fecal microbiota composition in adult men.
AB  - Resistant maltodextrin (RM) is a novel soluble, nonviscous dietary fiber. Its
      metabolizable energy (ME) and net energy (NE) values derived from nutrient
      balance studies are unknown, as is the effect of RM on fecal microbiota. A
      randomized, placebo-controlled, double-blind crossover study was conducted (n =
      14 men) to determine the ME and NE of RM and its influence on fecal excretion of
      macronutrients and microbiota. Participants were assigned to a sequence
      consisting of 3 treatment periods [24 d each: 0 g/d RM + 50 g/d maltodextrin and
      2 amounts of dietary RM (25 g/d RM + 25 g of maltodextrin/d and 50 g/d RM + 0 g/d
      maltodextrin)] and were provided all the foods they were to consume to maintain
      their body weight. After an adaptation period, excreta were collected during a 7
      d period. After the collection period, 24-h energy expenditure was measured.
      Fluorescence in situ hybridization, quantitative polymerase chain reaction, and
      454 titanium technology-based 16S rRNA sequencing were used to analyze fecal
      microbiota composition. Fecal amounts of energy (544, 662, 737 kJ/d), nitrogen
      (1.5, 1.8, 2.1 g/d), RM (0.3, 0.6, 1.2 g/d), and total carbohydrate (11.1, 14.2,
      16.2 g/d) increased with increasing dose (0, 25, 50 g) of RM (P < 0.0001). Fat
      excretion did not differ among treatments. The ME value of RM was 8.2 and 10.4
      kJ/g, and the NE value of RM was -8.2 and 2.0 kJ/g for the 25 and 50 g/d RM
      doses, respectively. Both doses of RM increased fecal wet weight (118, 148, 161
      g/d; P < 0.0001) and fecal dry weight (26.5, 32.0, 35.8 g/d; P < 0.0001) compared
      with the maltodextrin placebo. Total counts of fecal bacteria increased by 12%
      for the 25 g/d RM dose (P = 0.17) and 18% for the 50 g/d RM dose (P = 0.019). RM
      intake was associated with statistically significant increases (P < 0.001) in
      various operational taxonomic units matching closest to ruminococcus,
      eubacterium, lachnospiraceae, bacteroides, holdemania, and faecalibacterium,
      implicating RM in their growth in the gut. Our findings provide empirical data
      important for food labeling regulations related to the energy value of RM and
      suggest that RM increases fecal bulk by enhancing the excretion of nitrogen and
      carbohydrate and the growth of specific microbial populations. 

PMID- 24744315
TI  - Transcriptional regulation of the albumin gene depends on the removal of histone
      methylation marks by the FAD-dependent monoamine oxidase lysine-specific
      demethylase 1 in HepG2 human hepatocarcinoma cells.
AB  - Lysine-specific demethylase (LSD) 1 is an FAD-dependent demethylase that
      catalyzes the removal of methyl groups from lysine-4 in histone H3, thereby
      mediating gene repression. Here we tested the hypothesis that riboflavin
      deficiency causes a loss of LSD1 activity in HepG2 human hepatocarcinoma cells,
      leading to an accumulation of lysine-4-dimethylated histone H3 (H3K4me2) marks in
      the albumin promoter and aberrant upregulation of albumin expression. Cells were
      cultured in riboflavin-defined media providing riboflavin at concentrations
      representing moderately deficient (3.1 nmol/L), sufficient (12.6 nmol/L), and
      supplemented (301 nmol/L) cells in humans for 7 d. The efficacy of treatment was
      confirmed by assessing glutathione reductase activity and concentrations of
      reduced glutathione as markers of riboflavin status. LSD activity was 21% greater
      in riboflavin-supplemented cells compared with riboflavin-deficient and 
      sufficient cells. The loss of LSD activity was associated with a gain in the
      abundance of H3K4me2 marks in the albumin promoter; the abundance of H3K4me2
      marks was ~170% higher in riboflavin-deficient cells compared with sufficient and
      supplemented cells. The abundance of the repression mark, K9-trimethylated
      histone H3, was 38% lower in the albumin promoter of riboflavin-deficient cells
      compared with the other treatment groups. The expression of albumin mRNA was
      aberrantly increased by 200% in riboflavin-deficient cells compared with
      sufficient and supplemented cells. In conclusion, riboflavin deficiency impairs
      gene regulation by epigenetic mechanisms, mediated by a loss of LSD1 activity. 

PMID- 24744317
TI  - Iron-containing micronutrient supplementation of Chinese women with no or mild
      anemia during pregnancy improved iron status but did not affect perinatal anemia.
AB  - Universal prenatal daily iron-folic acid (IFA) and multiple micronutrient (MM)
      supplements are recommended to reduce the risk of low birth weight, maternal
      anemia, and iron deficiency (ID) during pregnancy, but the evidence of their
      effect on iron status among women with mild or no anemia is limited. The aim of
      this study was to describe the iron status [serum ferritin (SF), serum soluble
      transferrin receptor (sTfR), and body iron (BI)] before and after micronutrient
      supplementation during pregnancy. We examined 834 pregnant women with hemoglobin
      > 100 g/L at enrollment before 20 wk of gestation and with iron measurement data
      from a subset of a randomized, double-blind trial in China. Women were randomly
      assigned to take daily 400 MUg of folic acid (FA) (control), FA plus 30 mg of
      iron, or FA, iron, plus 13 additional MMs provided before 20 wk of gestation to
      delivery. Venous blood was collected in this subset during study enrollment
      (before 20 wk of gestation) and 28-32 wk of gestation. We found that, at 28-32 wk
      of gestation, compared with the FA group, both the IFA and MM groups had
      significantly lower prevalence of ID regardless of which indicator (SF, sTfR, or
      BI) was used for defining ID. The prevalence of ID at 28-32 wk of gestation for
      IFA, MM, and FA were 35.3%, 42.7%, and 59.6% by using low SF, 53.6%, 59.9%, and
      69.9% by using high sTfR, and 34.5%, 41.2%, and 59.6% by using low BI,
      respectively. However, there was no difference in anemia prevalence (hemoglobin <
      110 g/L) between FA and IFA or MM groups. We concluded that, compared with FA
      alone, prenatal IFA and MM supplements provided to women with no or mild anemia
      improved iron status later during pregnancy but did not affect perinatal anemia.
      This trial was registered at clinicaltrials.gov as NCT00137744. 

PMID- 24744318
TI  - Double-fortified salt is efficacious in improving indicators of iron deficiency
      in female Indian tea pickers.
AB  - Poor iron status affects 50% of Indian women and compromises work productivity,
      cognitive performance, and reproduction. Among the many strategies to reduce iron
      deficiency is the commercial fortification of iodized table salt with iron to
      produce a double-fortified salt (DFS). The objective of this study was to test
      the efficacy of DFS in reducing iron deficiency in rural women of reproductive
      age from northern West Bengal, India. The participants were 212 women between 18
      and 55 y of age who worked as full-time tea pickers on a large tea estate.
      Participants in the randomized, controlled, double-blind study were assigned to
      use either DFS or a control iodized salt for 7.5 to 9 mo. The DFS was fortified
      with 3.3-mg ferrous fumarate (1.1-mg elemental iron) per kg of iodized salt,
      whereas the control salt contained only iodine (47 mg/kg potassium iodate), and
      both salt varieties were distributed gratis to the families of participants at
      0.5 kg/mo for each 2 household members. At baseline, 53% of participants were
      anemic (hemoglobin <120 g/L), 25% were iron deficient (serum ferritin <12 MUg/L),
      and 23% were iron-deficient anemic. Also, 22% had a transferrin receptor
      concentration >8.6 mg/L and 22% had negative (<0.0 mg/kg) body iron stores. After
      9 mo the participants receiving DFS showed significant improvements compared with
      controls in hemoglobin (+2.4 g/L), ferritin (+0.13 log10 MUg/L), soluble
      transferrin receptor (-0.59 mg/L), and body iron (+1.43 mg/kg), with change in
      status analyzed by general linear models controlling for baseline values. This
      study demonstrated that DFS is an efficacious approach to improving iron status
      and should be further evaluated for effectiveness in the general population. This
      trial was registered at clinicaltrials.gov as NCT01032005. 

PMID- 24744320
TI  - Draft Genome Sequence of Streptomyces sp. Strain PRh5, a Novel Endophytic
      Actinomycete Isolated from Dongxiang Wild Rice Root.
AB  - Here, we report the draft genome sequence of Streptomyces sp. strain PRh5 (China
      Center for Type Culture Collection [CCTCC] number 2013487), which is used to
      produce nigericin and nocardamine. The genome sequence will allow for the
      characterization of the molecular mechanisms underlying its beneficial
      properties. 

PMID- 24744319
TI  - Caffeine and alcohol intakes and overall nutrient adequacy are associated with
      longitudinal cognitive performance among U.S. adults.
AB  - Among modifiable lifestyle factors, diet may affect cognitive health. Cross
      sectional and longitudinal associations may exist between dietary exposures
      [e.g., caffeine (mg/d), alcohol (g/d), and nutrient adequacy] and cognitive
      performance and change over time. This was a prospective cohort study, the
      Baltimore Longitudinal Study of Aging (n = 628-1305 persons depending on the
      cognitive outcome; ~2 visits/person). Outcomes included 10 cognitive scores,
      spanning various domains of cognition. Caffeine and alcohol intakes and a
      nutrient adequacy score (NAS) were estimated from 7-d food diaries. Among key
      findings, caffeine intake was associated with better baseline global cognition
      among participants with a baseline age (Agebase) of >=70 y. A higher NAS was
      associated with better baseline global cognition performance (overall, women,
      Agebase <70 y), better baseline verbal memory (immediate and delayed recall,
      Agebase >=70 y), and slower rate of decline or faster improvement in the
      attention domain (women). For an Agebase of <70 y, alcohol consumption was
      associated with slower improvement on letter fluency and global cognition over
      time. Conversely, for an Agebase of >=70 y and among women, alcohol intake was
      related to better baseline attention and working memory. In sum, patterns of diet
      and cognition associations indicate stratum-specific associations by sex and
      baseline age. The general observed trend was that of putative beneficial effects
      of caffeine intake and nutrient adequacy on domains of global cognition, verbal
      memory, and attention, and mixed effects of alcohol on domains of letter fluency,
      attention, and working memory. Further longitudinal studies conducted on larger
      samples of adults are needed to determine whether dietary factors individually or
      in combination are modifiers of cognitive trajectories among adults. 

PMID- 24744322
TI  - Genome Sequence of Luminous Piezophile Photobacterium phosphoreum ANT-2200.
AB  - Bacteria of the genus Photobacterium thrive worldwide in oceans and show
      substantially varied lifestyles, including free-living, commensal, pathogenic,
      symbiotic, and piezophilic. Here, we present the genome sequence of a luminous,
      piezophilic Photobacterium phosphoreum strain, ANT-2200, isolated from a water
      column at 2,200 m depth in the Mediterranean Sea. It is the first genomic
      sequence of the P. phosphoreum group. An analysis of the sequence provides
      insight into the adaptation of bacteria to the deep-sea habitat. 

PMID- 24744321
TI  - Draft Genome Sequence of Ochroconis constricta UM 578, Isolated from Human Skin
      Scraping.
AB  - Ochroconis constricta is a soilborne dematiaceous fungus that has never been
      reported to be associated with human infection. Here we report the first draft
      genome sequence of strain UM 578, isolated from human skin scraping. The genomic
      information revealed will contribute to a better understanding of this species. 

PMID- 24744323
TI  - Complete Genome Sequence of a Wild-Type Measles Virus Isolated during the Spring
      2013 Epidemic in Germany.
AB  - Measles virus induces an acute disease with rash and fever. Despite ongoing
      vaccination and elimination campaigns, the measles virus still sustains long
      lasting transmission chains in Europe. Here we report the complete genome
      sequence of a wild-type measles virus isolated from a patient in Munich
      (MVi/Muenchen.DEU/19.13[D8]) during a German measles outbreak in 2013. 

PMID- 24744324
TI  - Complete Genome Sequence of CHYJ130330, a Highly Virulent Strain of Porcine
      Epidemic Diarrhea Virus in South China.
AB  - Porcine epidemic diarrhea virus (PEDV) strain CHYJ130330 was isolated from
      southern China and shown to be highly virulent when inoculated into neonatal
      pigs. This report describes the complete genome sequence of CHYJ130330. These
      data will provide important insights into the variation of PEDV in China. 

PMID- 24744325
TI  - Full Genome Analysis of Influenza A(H1N1)pdm09 Virus Isolated from Peru, 2013.
AB  - The pandemic influenza A(H1N1)pdm09 virus has been reported in Peru since 2009.
      We report the whole-genome sequence analysis of a viral isolate from an infection
      case that occurred during an influenza outbreak in 2013. This strain shows novel
      hemagglutinin (HA) mutations that may cause an antigenic drift that diminishes
      the protective effect of the vaccine. 

PMID- 24744326
TI  - Genome Sequence of Fusarium graminearum Isolate CS3005.
AB  - Fusarium graminearum is one of the most important fungal pathogens of wheat,
      barley, and maize worldwide. This announcement reports the genome sequence of a
      highly virulent Australian isolate of this species to supplement the existing
      genome of the North American F. graminearum isolate Ph1. 

PMID- 24744327
TI  - Draft Genome Sequence of Campylobacter corcagiensis Strain CIT045T, a
      Representative of a Novel Campylobacter Species Isolated from Lion-Tailed
      Macaques (Macaca silenus).
AB  - Campylobacter corcagiensis CIT045(T) (=CCUG 64942(T), LMG 27932(T)), a new member
      of the Campylobacter genus, has recently been isolated from lion-tailed macaques
      in Cork, Ireland. To further characterize this new species and its potential
      pathogenicity, the genome sequence of C. corcagiensis was determined and is
      presented here. 

PMID- 24744328
TI  - Draft Genome Sequence of Methicillin-Resistant Staphylococcus aureus CUHK_188
      (ST188), a Health Care-Associated Bacteremic Isolate from Hong Kong.
AB  - We report the draft genome sequence of a methicillin-resistant Staphylococcus
      aureus strain designated CUHK_188, isolated from a bacteremic patient undergoing
      treatment at a university teaching hospital in Hong Kong. This strain belongs to
      sequence type 188 (ST188), with spa type t189 and staphylococcal cassette
      chromosome mec type V. 

PMID- 24744329
TI  - Draft Genome Sequence of Quorum-Sensing and Quorum-Quenching Pseudomonas
      aeruginosa Strain MW3a.
AB  - Pseudomonas aeruginosa has a broad range of habitation, from aquatic environments
      to human lungs. The coexistence of quorum-sensing and quorum-quenching activities
      occurs in P. aeruginosa strain MW3a. In this work, we present the draft genome
      sequence of P. aeruginosa MW3a, an interesting bacterium isolated from a marine
      environment. 

PMID- 24744330
TI  - Draft Genome Sequence of Bacillus pumilus Fairview, an Isolate Recovered from a
      Microbial Methanogenic Enrichment of Coal Seam Gas Formation Water from
      Queensland, Australia.
AB  - Despite its global abundance, Bacillus pumilus is poorly studied. The Fairview
      strain was obtained from a methanogenic anaerobic coal digester. The draft genome
      sequence was 3.8 Mbp long and contained 3,890 protein-coding genes. Like the SAFR
      032 strain, it includes B. pumilus-specific proteins that likely confer enhanced
      resistance to environmental stresses. 

PMID- 24744331
TI  - Complete Genome Sequences of Eight Helicobacter pylori Strains with Different
      Virulence Factor Genotypes and Methylation Profiles, Isolated from Patients with
      Diverse Gastrointestinal Diseases on Okinawa Island, Japan, Determined Using
      PacBio Single-Molecule Real-Time Technology.
AB  - We report the complete genome sequences of eight Helicobacter pylori strains
      isolated from patients with gastrointestinal diseases in Okinawa, Japan. Whole
      genome sequencing and DNA methylation detection were performed using the PacBio
      platform. De novo assembly determined a single, complete contig for each strain.
      Furthermore, methylation analysis identified virulence factor genotype-dependent
      motifs. 

PMID- 24744332
TI  - Complete Genome Sequence of Porcine Coronavirus HKU15 Strain IN2847 from the
      United States.
AB  - Porcine coronavirus HKU15 (PorCoV HKU15) was first detected in pigs with clinical
      diseases in February 2014 in the United States. Here, we report the complete
      genome sequence of Indiana strain IN2847, which might be useful for understanding
      the molecular profile of PorCoV HKU15. 

PMID- 24744333
TI  - Complete Genome Sequence of a Virulent Streptococcus agalactiae Strain, 138P,
      Isolated from Diseased Nile Tilapia.
AB  - Streptococcus agalactiae strain 138P was isolated from the kidney of diseased
      Nile tilapia in Idaho during a 2007 streptococcal disease outbreak. The full
      genome sequence of S. agalactiae 138P is 1,838,701 bp. The availability of this
      genome will allow comparative genomics analysis to identify genes for antigen
      discovery and vaccine development. 

PMID- 24744334
TI  - Genome Sequence of Streptomyces albulus PD-1, a Productive Strain for Epsilon
      Poly-L-Lysine and Poly-L-Diaminopropionic Acid.
AB  - Streptomyces albulus PD-1, a productive strain for epsilon-poly-l-lysine and poly
      l-diaminopropionic acid, was isolated from soils. We present the genome sequence
      of S. albulus PD-1, which may provide abundant information regarding the
      production of epsilon-poly-l-lysine and poly-l-diaminopropionic acid. 

PMID- 24744335
TI  - Genome sequences of two pseudoalteromonas strains isolated from the South china
      sea.
AB  - Two Pseudoalteromonas strains, SCSIO 04301 and SCSIO 11900, were isolated from
      the South China Sea, and both strains form biofilms. Here we present the draft
      genome sequences of these two strains, which will aid the study of marine
      microbes that are adapted to marine sediments or are associated with eukaryotic
      hosts. 

PMID- 24744336
TI  - Draft Genome Sequence of Mycobacterium austroafricanum DSM 44191.
AB  - We announce the draft genome sequence of Mycobacterium austroafricanum DSM
      44191(T) (= E9789-SA12441(T)), a non-tuberculosis species responsible for
      opportunistic infection. The genome described here has a size of 6,772,357 bp
      with a G+C content of 66.79% and contains 6,419 protein-coding genes and 112 RNA
      genes. 

PMID- 24744337
TI  - Complete Genomic Sequence of a Novel Porcine Circovirus 2 Strain, CC12.
AB  - The genome sequence of a novel porcine circovirus 2 strain (CC12) is composed of
      1,767 nucleotides, with two major open reading frames (ORFs). ORF1 encodes two
      replication-associated proteins (Rep and Rep') with the unique mutation N186S,
      and ORF2 encodes a viral capsid protein (Cap) with two rare mutations, R59K and
      A190T. 

PMID- 24744338
TI  - Draft Genome Sequence of Mycobacterium asiaticum Strain DSM 44297.
AB  - We report the draft genome sequence of Mycobacterium asiaticum strain DSM 44297,
      a tropical mycobacterium seldom responsible for human infection. The genome of M.
      asiaticum has a size of 5,935,986 bp, with a 66.03% G+C content, encoding 5,591
      proteins and 81 RNAs. 

PMID- 24744339
TI  - Iteradensovirus from the Monarch Butterfly, Danaus plexippus plexippus.
AB  - The 5,006-nucleotide (nt)-long genome of a new virus from monarch butterfly pupae
      was cloned and sequenced. It was flanked by inverted terminal repeats (ITRs) of
      239 nt with 163-nt hairpins. The monosense genome with three open reading frames
      is typical of the genus Iteradensovirus in the subfamily Densovirinae of the
      family Parvoviridae. 

PMID- 24744340
TI  - Genome Sequence of Bacillus pumilus MTCC B6033.
AB  - Bacillus pumilus is a Gram-positive, rod-shaped, aerobic bacterium isolated from
      the soil. B. pumilus strain B6033 was originally selected as a biocatalyst for
      the stereospecific oxidation of beta-lactams. Here, we present a 3.8-Mb assembly
      of its genome, which is the second fully assembled genome of a B. pumilus strain.

PMID- 24744341
TI  - Complete Genome of Bacillus megaterium Podophage Page.
AB  - Bacillus megaterium is a Gram-positive, spore-forming saprophytic inhabitant of
      diverse environments. It is a reservoir for industrial chemical production and is
      emerging as a model organism for studying sporulation and protein localization.
      Here, we introduce the complete genome of Page, a novel podophage infecting B.
      megaterium. 

PMID- 24744342
TI  - Complete Genome Sequence of the Treponema pallidum subsp. pallidum Sea81-4
      Strain.
AB  - Using the rabbit model of syphilis, the Sea81-4 strain of Treponema pallidum
      subsp. pallidum has been found to be more likely than other strains to invade the
      central nervous system (CNS). To identify possible explanations for this
      important phenotype at the genomic level, we sequenced the Sea81-4 strain genome.

PMID- 24744343
TI  - Genome Sequence of Salt-Tolerant Bacillus safensis Strain VK, Isolated from
      Saline Desert Area of Gujarat, India.

PMID- 24744344
TI  - A workplace colorectal cancer screening program in firefighters: lessons learned.
AB  - BACKGROUND: Although colorectal cancer (CRC) screening is widely recommended,
      screening rates remain low. Workplace interventions have the potential to
      increase rates of screening. AIMS: To evaluate the impact of a workplace CRC
      screening program targeting active duty and retired firefighters. METHODS: A
      letter, a fecal immunochemical test (FIT) kit and a survey were mailed to all
      active duty and retired San Francisco firefighters aged 40 and older during 2008
      09. The survey included questions about CRC risk factors and prior CRC screening
      tests. The primary outcome was return of the completed FIT. RESULTS: FIT kits and
      surveys were sent to 1203 firefighters. In total, 445 individuals (37%) completed
      the survey, and 400 (33%) completed the FIT. Forty-five per cent of respondents
      had had a stool test for blood at some time, although few (8%) had had it within
      the past year. Thirty-six per cent of respondents said they had had a
      sigmoidoscopy at some time, although only 15% had had it within the past 5 years
      and 37% within the past 10 years. Among those aged 50 and older, 59% had had a
      test for colon cancer at some time. CONCLUSIONS: A workplace intervention can
      increase CRC screening rates in firefighters. Future studies should focus on the
      long-term sustainability of this type of program.

PMID- 24744345
TI  - Influenza and the live poultry trade.

PMID- 24744350
TI  - Fusion. U.S. support for ITER wavers as costs spiral.

PMID- 24744351
TI  - Toxicology. 'Humanized' mouse detects deadly drug side effects.

PMID- 24744352
TI  - Epigenetics. Ancient DNA holds clues to gene activity in extinct humans.

PMID- 24744353
TI  - Climate science. More sophisticated forecasts yield glimmer of hope in climate
      gloom.

PMID- 24744354
TI  - Astronomy. Almost-Earth tantalizes astronomers with promise of worlds to come.

PMID- 24744355
TI  - Into the maelstrom.

PMID- 24744356
TI  - Climate discussion echoes tobacco debate.

PMID- 24744357
TI  - Integrating psychological treatment approaches.

PMID- 24744358
TI  - Uganda homosexuality report in context.

PMID- 24744360
TI  - Life in science. Weeds making waves.

PMID- 24744361
TI  - Science and regulation. Particulate matter matters.

PMID- 24744362
TI  - Ecology. Avoiding (re)extinction.

PMID- 24744363
TI  - Materials science. Exploring the interface of graphene and biology.

PMID- 24744364
TI  - Applied physics. Refractory plasmonics.

PMID- 24744365
TI  - Neuroscience. Myelin--more than insulation.

PMID- 24744366
TI  - Ecology. Novelty trumps loss in global biodiversity.

PMID- 24744367
TI  - Plant science. Paired plant immune receptors.

PMID- 24744369
TI  - KOI-3278: a self-lensing binary star system.
AB  - Over 40% of Sun-like stars are bound in binary or multistar systems. Stellar
      remnants in edge-on binary systems can gravitationally magnify their companions,
      as predicted 40 years ago. By using data from the Kepler spacecraft, we report
      the detection of such a "self-lensing" system, in which a 5-hour pulse of 0.1%
      amplitude occurs every orbital period. The white dwarf stellar remnant and its
      Sun-like companion orbit one another every 88.18 days, a long period for a white
      dwarf-eclipsing binary. By modeling the pulse as gravitational magnification
      (microlensing) along with Kepler's laws and stellar models, we constrain the mass
      of the white dwarf to be ~63% of the mass of our Sun. Further study of this
      system, and any others discovered like it, will help to constrain the physics of
      white dwarfs and binary star evolution. 

PMID- 24744368
TI  - A critical period of sleep for development of courtship circuitry and behavior in
      Drosophila.
AB  - Most animals sleep more early in life than in adulthood, but the function of
      early sleep is not known. Using Drosophila, we found that increased sleep in
      young flies was associated with an elevated arousal threshold and resistance to
      sleep deprivation. Excess sleep results from decreased inhibition of a sleep
      promoting region by a specific dopaminergic circuit. Experimental hyperactivation
      of this circuit in young flies results in sleep loss and lasting deficits in
      adult courtship behaviors. These deficits are accompanied by impaired development
      of a single olfactory glomerulus, VA1v, which normally displays extensive sleep
      dependent growth after eclosion. Our results demonstrate that sleep promotes
      normal brain development that gives rise to an adult behavior critical for
      species propagation and suggest that rapidly growing regions of the brain are
      most susceptible to sleep perturbations early in life. 

PMID- 24744370
TI  - An Earth-sized planet in the habitable zone of a cool star.
AB  - The quest for Earth-like planets is a major focus of current exoplanet research.
      Although planets that are Earth-sized and smaller have been detected, these
      planets reside in orbits that are too close to their host star to allow liquid
      water on their surfaces. We present the detection of Kepler-186f, a 1.11 +/- 0.14
      Earth-radius planet that is the outermost of five planets, all roughly Earth
      sized, that transit a 0.47 +/- 0.05 solar-radius star. The intensity and spectrum
      of the star's radiation place Kepler-186f in the stellar habitable zone, implying
      that if Kepler-186f has an Earth-like atmosphere and water at its surface, then
      some of this water is likely to be in liquid form. 

PMID- 24744371
TI  - Strong increase of T(c) of Sr2RuO4 under both tensile and compressive strain.
AB  - A sensitive probe of unconventional order is its response to a symmetry-breaking
      field. To probe the proposed p(x) +/- ip(y) topological superconducting state of
      Sr2RuO4, we have constructed an apparatus capable of applying both compressive
      and tensile strains of up to 0.23%. Strains applied along ?100? crystallographic
      directions yield a strong, strain-symmetric increase in the superconducting
      transition temperature T(c). ?110? strains give a much weaker, mostly
      antisymmetric response. As well as advancing the understanding of the
      superconductivity of Sr2RuO4, our technique has potential applicability to a wide
      range of problems in solid-state physics.

PMID- 24744372
TI  - Ultimate permeation across atomically thin porous graphene.
AB  - A two-dimensional (2D) porous layer can make an ideal membrane for separation of
      chemical mixtures because its infinitesimal thickness promises ultimate
      permeation. Graphene--with great mechanical strength, chemical stability, and
      inherent impermeability--offers a unique 2D system with which to realize this
      membrane and study the mass transport, if perforated precisely. We report highly
      efficient mass transfer across physically perforated double-layer graphene,
      having up to a few million pores with narrowly distributed diameters between less
      than 10 nanometers and 1 micrometer. The measured transport rates are in
      agreement with predictions of 2D transport theories. Attributed to its atomic
      thicknesses, these porous graphene membranes show permeances of gas, liquid, and
      water vapor far in excess of those shown by finite-thickness membranes,
      highlighting the ultimate permeation these 2D membranes can provide.

PMID- 24744373
TI  - Missing gas-phase source of HONO inferred from Zeppelin measurements in the
      troposphere.
AB  - Gaseous nitrous acid (HONO) is an important precursor of tropospheric hydroxyl
      radicals (OH). OH is responsible for atmospheric self-cleansing and controls the
      concentrations of greenhouse gases like methane and ozone. Due to lack of
      measurements, vertical distributions of HONO and its sources in the troposphere
      remain unclear. Here, we present a set of observations of HONO and its budget
      made onboard a Zeppelin airship. In a sunlit layer separated from Earth's surface
      processes by temperature inversion, we found high HONO concentrations providing
      evidence for a strong gas-phase source of HONO consuming nitrogen oxides and
      potentially hydrogen oxide radicals. The observed properties of this production
      process suggest that the generally assumed impact of HONO on the abundance of OH
      in the troposphere is substantially overestimated. 

PMID- 24744374
TI  - Assemblage time series reveal biodiversity change but not systematic loss.
AB  - The extent to which biodiversity change in local assemblages contributes to
      global biodiversity loss is poorly understood. We analyzed 100 time series from
      biomes across Earth to ask how diversity within assemblages is changing through
      time. We quantified patterns of temporal alpha diversity, measured as change in
      local diversity, and temporal beta diversity, measured as change in community
      composition. Contrary to our expectations, we did not detect systematic loss of
      alpha diversity. However, community composition changed systematically through
      time, in excess of predictions from null models. Heterogeneous rates of
      environmental change, species range shifts associated with climate change, and
      biotic homogenization may explain the different patterns of temporal alpha and
      beta diversity. Monitoring and understanding change in species composition should
      be a conservation priority. 

PMID- 24744375
TI  - Structural basis for assembly and function of a heterodimeric plant immune
      receptor.
AB  - Cytoplasmic plant immune receptors recognize specific pathogen effector proteins
      and initiate effector-triggered immunity. In Arabidopsis, the immune receptors
      RPS4 and RRS1 are both required to activate defense to three different pathogens.
      We show that RPS4 and RRS1 physically associate. Crystal structures of the N
      terminal Toll-interleukin-1 receptor/resistance (TIR) domains of RPS4 and RRS1,
      individually and as a heterodimeric complex (respectively at 2.05, 1.75, and 2.65
      angstrom resolution), reveal a conserved TIR/TIR interaction interface. We show
      that TIR domain heterodimerization is required to form a functional RRS1/RPS4
      effector recognition complex. The RPS4 TIR domain activates effector-independent
      defense, which is inhibited by the RRS1 TIR domain through the heterodimerization
      interface. Thus, RPS4 and RRS1 function as a receptor complex in which the two
      components play distinct roles in recognition and signaling. 

PMID- 24744376
TI  - Crystal structure of a claudin provides insight into the architecture of tight
      junctions.
AB  - Tight junctions are cell-cell adhesion structures in epithelial cell sheets that
      surround organ compartments in multicellular organisms and regulate the
      permeation of ions through the intercellular space. Claudins are the major
      constituents of tight junctions and form strands that mediate cell adhesion and
      function as paracellular barriers. We report the structure of mammalian claudin
      15 at a resolution of 2.4 angstroms. The structure reveals a characteristic beta
      sheet fold comprising two extracellular segments, which is anchored to a
      transmembrane four-helix bundle by a consensus motif. Our analyses suggest
      potential paracellular pathways with distinctive charges on the extracellular
      surface, providing insight into the molecular basis of ion homeostasis across
      tight junctions. 

PMID- 24744377
TI  - The structural basis of pathogenic subgenomic flavivirus RNA (sfRNA) production.
AB  - Flaviviruses are emerging human pathogens and worldwide health threats. During
      infection, pathogenic subgenomic flaviviral RNAs (sfRNAs) are produced by
      resisting degradation by the 5'->3' host cell exonuclease Xrn1 through an unknown
      RNA structure-based mechanism. Here, we present the crystal structure of a
      complete Xrn1-resistant flaviviral RNA, which contains interwoven pseudoknots
      within a compact structure that depends on highly conserved nucleotides. The
      RNA's three-dimensional topology creates a ringlike conformation, with the 5' end
      of the resistant structure passing through the ring from one side of the fold to
      the other. Disruption of this structure prevents formation of sfRNA during
      flaviviral infection. Thus, sfRNA formation results from an RNA fold that
      interacts directly with Xrn1, presenting the enzyme with a structure that
      confounds its helicase activity. 

PMID- 24744378
TI  - The STAT3-binding long noncoding RNA lnc-DC controls human dendritic cell
      differentiation.
AB  - Long noncoding RNAs (lncRNAs) play important roles in diverse biological
      processes; however, few have been identified that regulate immune cell
      differentiation and function. Here, we identified lnc-DC, which was exclusively
      expressed in human conventional dendritic cells (DCs). Knockdown of lnc-DC
      impaired DC differentiation from human monocytes in vitro and from mouse bone
      marrow cells in vivo and reduced capacity of DCs to stimulate T cell activation.
      lnc-DC mediated these effects by activating the transcription factor STAT3
      (signal transducer and activator of transcription 3). lnc-DC bound directly to
      STAT3 in the cytoplasm, which promoted STAT3 phosphorylation on tyrosine-705 by
      preventing STAT3 binding to and dephosphorylation by SHP1. Our work identifies a
      lncRNA that regulates DC differentiation and also broadens the known mechanisms
      of lncRNA action. 

PMID- 24744379
TI  - Enhancing depression mechanisms in midbrain dopamine neurons achieves homeostatic
      resilience.
AB  - Typical therapies try to reverse pathogenic mechanisms. Here, we describe
      treatment effects achieved by enhancing depression-causing mechanisms in ventral
      tegmental area (VTA) dopamine (DA) neurons. In a social defeat stress model of
      depression, depressed (susceptible) mice display hyperactivity of VTA DA neurons,
      caused by an up-regulated hyperpolarization-activated current (I(h)). Mice
      resilient to social defeat stress, however, exhibit stable normal firing of these
      neurons. Unexpectedly, resilient mice had an even larger I(h), which was observed
      in parallel with increased potassium (K(+)) channel currents. Experimentally
      further enhancing Ih or optogenetically increasing the hyperactivity of VTA DA
      neurons in susceptible mice completely reversed depression-related behaviors, an
      antidepressant effect achieved through resilience-like, projection-specific
      homeostatic plasticity. These results indicate a potential therapeutic path of
      promoting natural resilience for depression treatment.

PMID- 24744380
TI  - Distinct profiles of myelin distribution along single axons of pyramidal neurons
      in the neocortex.
AB  - Myelin is a defining feature of the vertebrate nervous system. Variability in the
      thickness of the myelin envelope is a structural feature affecting the conduction
      of neuronal signals. Conversely, the distribution of myelinated tracts along the
      length of axons has been assumed to be uniform. Here, we traced high-throughput
      electron microscopy reconstructions of single axons of pyramidal neurons in the
      mouse neocortex and built high-resolution maps of myelination. We find that
      individual neurons have distinct longitudinal distribution of myelin. Neurons in
      the superficial layers displayed the most diversified profiles, including a new
      pattern where myelinated segments are interspersed with long, unmyelinated
      tracts. Our data indicate that the profile of longitudinal distribution of myelin
      is an integral feature of neuronal identity and may have evolved as a strategy to
      modulate long-distance communication in the neocortex. 

PMID- 24744382
TI  - The effect of spaceflight on mouse olfactory bulb volume, neurogenesis, and cell
      death indicates the protective effect of novel environment.
AB  - Space missions necessitate physiological and psychological adaptations to
      environmental factors not present on Earth, some of which present significant
      risks for the central nervous system (CNS) of crewmembers. One CNS region of
      interest is the adult olfactory bulb (OB), as OB structure and function are
      sensitive to environmental- and experience-induced regulation. It is currently
      unknown how the OB is altered by spaceflight. In this study, we evaluated OB
      volume and neurogenesis in mice shortly after a 13-day flight on Space Shuttle
      Atlantis [Space Transport System (STS)-135] relative to two groups of control
      mice maintained on Earth. Mice housed on Earth in animal enclosure modules that
      mimicked the conditions onboard STS-135 (AEM-Ground mice) had greater OB volume
      relative to mice maintained in standard housing on Earth (Vivarium mice),
      particularly in the granule (GCL) and glomerular (GL) cell layers. AEM-Ground
      mice also had more OB neuroblasts and fewer apoptotic cells relative to Vivarium
      mice. However, the AEM-induced increase in OB volume and neurogenesis was not
      seen in STS-135 mice (AEM-Flight mice), suggesting that spaceflight may have
      negated the positive effects of the AEM. In fact, when OB volume of AEM-Flight
      mice was considered, there was a greater density of apoptotic cells relative to
      AEM-Ground mice. Our findings suggest that factors present during spaceflight
      have opposing effects on OB size and neurogenesis, and provide insight into
      potential strategies to preserve OB structure and function during future space
      missions. 

PMID- 24744383
TI  - The serpentine path to a novel mechanism-based inhibitor of acute inflammatory
      lung injury.
AB  - The Comroe lecture on which this review is based described my research path
      during the past 45 years, beginning with studies of oxidant stress (hyperoxia)
      and eventuating in the discovery of a synthetic inhibitor of phospholipase A2
      activity (called MJ33) that prevents acute lung injury in mice exposed to
      lipopolysaccharide. In between were studies of lung ischemia, lung surfactant
      metabolism, the protein peroxiredoxin 6 and its phospholipase A2 activity, and
      mechanisms for NADPH oxidase activation. These seemingly unrelated research
      activities provided the nexus for identification of a novel target and a
      potentially novel therapeutic agent for prevention or treatment of acute lung
      injury. 

PMID- 24744384
TI  - Aerobic exercise training reduces arterial stiffness in metabolic syndrome.
AB  - The metabolic syndrome (MetS) is associated with a threefold increase risk of
      cardiovascular disease (CVD) mortality partly due to increased arterial
      stiffening. We compared the effects of aerobic exercise training on arterial
      stiffening/mechanics in MetS subjects without overt CVD or type 2 diabetes. MetS
      and healthy control (Con) subjects underwent 8 wk of exercise training (ExT; 11
      MetS and 11 Con) or remained inactive (11 MetS and 10 Con). The following
      measures were performed pre- and postintervention: radial pulse wave analysis
      (applanation tonometry) was used to measure augmentation pressure and index,
      central pressures, and an estimate of myocardial efficiency; arterial stiffness
      was assessed from carotid-femoral pulse-wave velocity (cfPWV, applanation
      tonometry); carotid thickness was assessed from B-mode ultrasound; and peak
      aerobic capacity (gas exchange) was performed in the seated position. Plasma
      matrix metalloproteinases (MMP) and CVD risk (Framingham risk score) were also
      assessed. cfPWV was reduced (P < 0.05) in MetS-ExT subjects (7.9 +/- 0.6 to 7.2
      +/- 0.4 m/s) and Con-ExT (6.6 +/- 1.8 to 5.6 +/- 1.6 m/s). Exercise training
      reduced (P < 0.05) central systolic pressure (116 +/- 5 to 110 +/- 4 mmHg),
      augmentation pressure (9 +/- 1 to 7 +/- 1 mmHg), augmentation index (19 +/- 3 to
      15 +/- 4%), and improved myocardial efficiency (155 +/- 8 to 168 +/- 9), but only
      in the MetS group. Aerobic capacity increased (P < 0.05) in MetS-ExT (16.6 +/-
      1.0 to 19.9 +/- 1.0) and Con-ExT subjects (23.8 +/- 1.6 to 26.3 +/- 1.6). MMP-1
      and -7 were correlated with cfPWV, and both MMP-1 and -7 were reduced post-ExT in
      MetS subjects. These findings suggest that some of the pathophysiological changes
      associated with MetS can be improved after aerobic exercise training, thereby
      lowering their cardiovascular risk. 

PMID- 24744385
TI  - Influence of cerebrovascular resistance on the dynamic relationship between blood
      pressure and cerebral blood flow in humans.
AB  - We examined the hypothesis that changes in the cerebrovascular resistance index
      (CVRi), independent of blood pressure (BP), will influence the dynamic
      relationship between BP and cerebral blood flow in humans. We altered CVRi with
      (via controlled hyperventilation) and without [via indomethacin (INDO, 1.2
      mg/kg)] changes in PaCO2. Sixteen subjects (12 men, 27 +/- 7 yr) were tested on
      two occasions (INDO and hypocapnia) separated by >48 h. Each test incorporated
      seated rest (5 min), followed by squat-stand maneuvers to increase BP variability
      and improve assessment of the pressure-flow dynamics using linear transfer
      function analysis (TFA). Beat-to-beat BP, middle cerebral artery velocity (MCAv),
      posterior cerebral artery velocity (PCAv), and end-tidal Pco2 were monitored.
      Dynamic pressure-flow relations were quantified using TFA between BP and
      MCAv/PCAv in the very low and low frequencies through the driven squat-stand
      maneuvers at 0.05 and 0.10 Hz. MCAv and PCAv reductions by INDO and hypocapnia
      were well matched, and CVRi was comparably elevated (P < 0.001). During the squat
      stand maneuvers (0.05 and 0.10 Hz), the point estimates of absolute gain were
      universally reduced, and phase was increased under both conditions. In addition
      to an absence of regional differences, our findings indicate that alterations in
      CVRi independent of PaCO2 can alter cerebral pressure-flow dynamics. These
      findings are consistent with the concept of CVRi being a key factor that should
      be considered in the correct interpretation of cerebral pressure-flow dynamics as
      indexed using TFA metrics. 

PMID- 24744386
TI  - Changes in respiratory activity induced by mastication during oral breathing in
      humans.
AB  - We examined the effect of oral breathing on respiratory movements, including the
      number of respirations and the movement of the thoracic wall at rest and while
      chewing gum. Forty normal nose breathers were selected by detecting expiratory
      airflow from the mouth using a CO2 sensor. Chest measurements were recorded using
      a Piezo respiratory belt transducer, and electromyographic (EMG) activity of the
      masseter and trapezius muscles were recorded at rest and while chewing gum during
      nasal or oral breathing. Oral breathing was introduced by completely occluding
      the nostrils with a nose clip. During oral breathing, the respiration rate was
      significantly lower while chewing gum than while at rest (P < 0.05). While
      chewing gum, the respiration rate was significantly lower during oral breathing
      than during nasal breathing (P < 0.05). During oral breathing, thoracic movement
      was significantly higher while chewing gum than while at rest (P < 0.05).
      Thoracic movement was significantly greater during oral breathing than during
      nasal breathing (P < 0.05). The trapezius muscle exhibited significant EMG
      activity when chewing gum during oral breathing. The activity of the trapezius
      muscle coincided with increased movement of the thoracic wall. Chewing food while
      breathing through the mouth interferes with and decreases the respiratory cycle
      and promotes unusual respiratory movement of the thoracic wall, which is directed
      by the activity of accessory muscles of respiration. 

PMID- 24744387
TI  - Upper airway mechanics in chronic spinal cord injury during sleep.
AB  - Sleep-disordered breathing has been shown to be more prevalent in patients with
      spinal cord injury (SCI) than the general population. The pathogenesis of
      increased sleep-disordered breathing in individuals with chronic SCI is unknown.
      The purpose of this study is to determine whether SCI level affects upper airway
      (UA) collapsibility and neuromuscular compensatory responses to obstruction.
      Twenty-four participants (8 cervical SCI, 8 thoracic SCI, and 8 controls) were
      studied. The ventilation, timing, UA resistance, and pharyngeal collapsibility,
      defined by critical closing pressure, were determined during non-rapid eye
      movement sleep. Inspiratory duty cycle and minute ventilation were observed in
      response to increasing severity of UA obstruction. Compared with controls, both
      cervical and thoracic SCI participants demonstrated elevated passive critical
      closing pressure (0.5 +/- 2.2 and 0.9 +/- 2.7 vs. -2.5 +/- 1.0 cmH2O,
      respectively; P = 0.01). No difference in UA resistance was observed between
      groups. Cervical and thoracic SCI individuals exhibited a similar degree of
      hypoventilation and dose-dependent increase in inspiratory duty cycle in response
      to UA obstruction. Passive UA collapsibility is increased in both cervical and
      thoracic SCI compared with control. The neuromuscular compensatory responses to
      UA obstruction during sleep are preserved in chronic SCI and are independent of
      the level of injury. 

PMID- 24744388
TI  - Eccentric exercise: many questions unanswered.

PMID- 24744390
TI  - Association of sarcopenia with short- and long-term mortality in older adults
      admitted to acute care wards: results from the CRIME study.
AB  - BACKGROUND: Sarcopenia is a common condition in older and frail populations, and
      it has been associated with adverse health outcomes. However, impact of
      sarcopenia on mortality in hospitalized older adults has rarely been evaluated.
      Aim of the present study was to investigate the association between sarcopenia
      and mortality during hospital stay and at 1 year after discharge in older
      individuals admitted to acute care wards. METHODS: This is a multicentre
      observational study involving 770 in-hospital patients. Muscle mass was
      quantified with the bioelectrical impedance analysis. The diagnosis of sarcopenia
      was based on the algorithm proposed by the European Working Group on Sarcopenia
      in Older People (EWGSOP). After discharge, participants were followed for 1 year.
      Mortality was assessed during hospital stay and during 1-year follow-up. RESULTS:
      Within the 770 participants (mean age: 81 +/- 7 years, 56% women), sarcopenia was
      present in 214 (28%) of them, 22 participants died during hospital stay, and 113
      in the year after discharge. Participants with sarcopenia had a significantly
      higher in-hospital (6% vs 2%; p = .007) and 1-year mortality (26% vs 14%; p <
      .001) as compared with participants without sarcopenia. After adjusting for
      potential confounders, sarcopenia resulted significantly associated with in
      hospital (hazard ratio: 3.45; 95% CI: 1.35-8.86) and 1-year mortality (hazard
      ratio: 1.59; 95% CI: 1.10-2.41). CONCLUSIONS: Sarcopenia is a prevalent condition
      among older adults admitted to acute care wards and it is associated with
      increased short- and long-term mortality in hospitalized older adults.

PMID- 24744389
TI  - Role of nitric oxide-containing factors in the ventilatory and cardiovascular
      responses elicited by hypoxic challenge in isoflurane-anesthetized rats.
AB  - Exposure to hypoxia elicits changes in mean arterial blood pressure (MAP), heart
      rate, and frequency of breathing (fR). The objective of this study was to
      determine the role of nitric oxide (NO) in the cardiovascular and ventilatory
      responses elicited by brief exposures to hypoxia in isoflurane-anesthetized rats.
      The rats were instrumented to record MAP, heart rate, and fR and then exposed to
      90 s episodes of hypoxia (10% O2, 90% N2) before and after injection of vehicle,
      the NO synthase inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME), or the
      inactive enantiomer D-NAME (both at 50 MUmol/kg iv). Each episode of hypoxia
      elicited a decrease in MAP, bidirectional changes in heart rate (initial increase
      and then a decrease), and an increase in fR. These responses were similar before
      and after injection of vehicle or D-NAME. In contrast, the hypoxia-induced
      decreases in MAP were attenuated after administration of L-NAME. The initial
      increases in heart rate during hypoxia were amplified whereas the subsequent
      decreases in heart rate were attenuated in L-NAME-treated rats. Finally, the
      hypoxia-induced increases in fR were virtually identical before and after
      administration of L-NAME. These findings suggest that NO factors play a vital
      role in the expression of the cardiovascular but not the ventilatory responses
      elicited by brief episodes of hypoxia in isoflurane-anesthetized rats. Based on
      existing evidence that NO factors play a vital role in carotid body and central
      responses to hypoxia in conscious rats, our findings raise the novel possibility
      that isoflurane blunts this NO-dependent signaling.

PMID- 24744391
TI  - Sleep and executive function in older women: the moderating effect of physical
      activity.
AB  - BACKGROUND: Sleep and physical activity are both important for cognition.
      However, few cognitive function studies include comprehensive measurement of both
      sleep and physical activity. The purpose of this study was to examine the
      independent and interactive associations of sleep and physical activity in
      relation to cognitive function in older women. METHODS: A subset of 121 women
      from the Healthy Women Study, mean age 73.3 +/- 1.7 years, wore an actigraphy
      sleep monitor, physical activity accelerometer, and kept sleep and physical
      activity diaries for 7 consecutive days. Executive function was measured with the
      Digit Symbol Substitution Test and the Trail Making Test B. Verbal fluency was
      assessed with a word generation task. RESULTS: In adjusted models, greater
      actigraphy-assessed sleep efficiency was associated with more correct responses
      on the Digit Symbol Substitution Test (beta = 0.35, SE = 0.15, p < 0.02). Sleep
      was not associated with verbal fluency. A significant interaction (p < 0.05) was
      observed between accelerometer-assessed physical activity and actigraphy-assessed
      sleep efficiency. Specifically, lower sleep efficiency was associated with poorer
      performance on both the Digit Symbol Substitution Test and the Trail Making Test
      B among women with low levels of physical activity but not among women with high
      levels of physical activity. CONCLUSIONS: Our findings suggest that greater
      levels of physical activity may attenuate the negative impact of poor sleep on
      executive function in older women, with the clearest effects observed using
      direct measurements of sleep and physical activity.

PMID- 24744395
TI  - Are There Differences Between the Upper and Lower Parts of the Superficial
      Musculoaponeurotic System? A Preliminary Biomechanical Study.
AB  - BACKGROUND: The superficial musculoaponeurotic system (SMAS) becomes thinner and
      gradually disappears from the midface. In rhytidectomy, manipulation of the SMAS
      occurs in the lateral area, and previous research has focused primarily on the
      SMAS region as a whole. OBJECTIVES: In this preliminary study, the authors
      compared the viscoelasticity of the upper and lower regions of the SMAS using
      biomechanical techniques. METHODS: Two adjacent projection regions of the SMAS
      were designated: region 1 and region 2, representing the upper and lower parts,
      respectively. The SMAS tissues from 8 fresh-frozen cadaver heads were cut into 64
      samples before biomechanical testing, and the following variables were recorded
      for subsequent analysis: stress-strain curve, elastic modulus, ultimate strength,
      and elongation at break. RESULTS: The stiffness of region 1 was markedly greater
      than that of region 2. Energy dissipation was greater in region 2. Elastic
      modulus and ultimate strength were significantly higher for region 1, and
      elongation at break was longer in region 2. The fit curve of the 2 regions
      deviated markedly. CONCLUSIONS: The biomechanical properties of the upper and
      lower regions of the lateral SMAS are functionally different. Such knowledge will
      help refine the planning and design of facial surgery and improve outcomes for
      patients who undergo rhytidectomy.

PMID- 24744394
TI  - Porcine skeletal muscle-derived multipotent PW1pos/Pax7neg interstitial cells:
      isolation, characterization, and long-term culture.
AB  - Developing effective strategies for the regeneration of solid tissue requires an
      understanding of the biology underlying the tissue's endogenous repair
      mechanisms. PW1/Peg3(pos)/Pax7(neg) skeletal muscle-derived interstitial
      progenitor cells (PICs) were first identified recently in the interstitium of
      murine skeletal muscle and shown to contribute to muscle fiber regeneration in
      vivo. PICs, therefore, represent a novel candidate resident progenitor cell for
      muscle regeneration. To explore the potential of these cells for clinical
      translation, we must ascertain the presence of PICs in larger mammalian species
      and identify criteria to successfully isolate and expand this population. In this
      study, we report the isolation, characterization, and maintenance of multipotent
      PICs from juvenile porcine skeletal muscle. We show that porcine PICs can be
      reproducibly isolated from skeletal muscle, express stem/progenitor cell markers,
      and have a stable phenotype and karyotype through multiple passages. Furthermore,
      porcine PICs are clonogenic and multipotent, giving rise to skeletal
      myoblast/myotubes, smooth muscle, and endothelial cells. In addition, PICs can be
      induced to differentiate into cardiomyocyte-like cells. These results
      demonstrate, in an animal model with size and physiology extrapolatable to the
      human, that porcine skeletal muscle-derived PW1(pos)/Pax7(neg) PICs are a source
      of stem/progenitor cells. These findings open new avenues for a variety of solid
      tissue engineering and regeneration using a single multipotent stem cell type
      isolated from an easily accessible source, such as skeletal muscle. 

PMID- 24744393
TI  - Human neural stem cells survive long term in the midbrain of dopamine-depleted
      monkeys after GDNF overexpression and project neurites toward an appropriate
      target.
AB  - Transplanted multipotent human fetal neural stem cells (hfNSCs) significantly
      improved the function of parkinsonian monkeys in a prior study primarily by
      neuroprotection, with only 3%-5% of cells expressing a dopamine (DA) phenotype.
      In this paper, we sought to determine whether further manipulation of the neural
      microenvironment by overexpression of a developmentally critical molecule, glial
      cell-derived neurotrophic factor (GDNF), in the host striatum could enhance DA
      differentiation of hfNSCs injected into the substantia nigra and elicit growth of
      their axons to the GDNF-expressing target. hfNSCs were transplanted into the
      midbrain of 10 green monkeys exposed to 1-methyl-4-phenyl-1,2,3,6-tetrahydro
      pyridine. GDNF was delivered concomitantly to the striatum via an adeno
      associated virus serotype 5 vector, and the fate of grafted cells was assessed
      after 11 months. Donor cells remained predominantly within the midbrain at the
      injection site and sprouted numerous neurofilament-immunoreactive fibers that
      appeared to course rostrally toward the striatum in parallel with tyrosine
      hydroxylase-immunoreactive fibers from the host substantia nigra but did not
      mature into DA neurons. This work suggests that hfNSCs can generate neurons that
      project long fibers in the adult primate brain. However, in the absence of region
      specific signals and despite GDNF overexpression, hfNSCs did not differentiate
      into mature DA neurons in large numbers. It is encouraging, however, that the
      adult primate brain appeared to retain axonal guidance cues. We believe that
      transplantation of stem cells, specifically instructed ex vivo to yield DA
      neurons, could lead to reconstruction of some portion of the nigrostriatal
      pathway and prove beneficial for the parkinsonian condition. 

PMID- 24744392
TI  - Concise review: mesenchymal stromal cells used for periodontal regeneration: a
      systematic review.
AB  - Periodontitis is a chronic infectious disease of the soft and hard tissues
      supporting the teeth. Recent advances in regenerative medicine and stem cell
      biology have paved the way for periodontal tissue engineering. Mesenchymal
      stromal cells (MSCs) delivered in situ to periodontal defects may exert their
      effects at multiple levels, including neovascularization, immunomodulation, and
      tissue regeneration. This systematic review had two goals: (a) to objectively
      quantify key elements for efficacy and safety of MSCs used for periodontal
      regeneration and (b) to identify patterns in the existing literature to explain
      differences between studies and suggest recommendations for future research. This
      systematic review provided good evidence of the capacity of MSCs to regenerate
      periodontal tissues in animals; however, experimentally generated defects used in
      animal studies do not sufficiently mimic the pathophysiology of periodontitis in
      humans. Moreover, the safety of such interventions in humans still needs to be
      studied. There were marked differences between experimental and control groups
      that may be influenced by characteristics that are crucial to address before
      translation to human clinical trials. We suggest that the appropriate combination
      of cell source, carrier type, and biomolecules, as well as the inclusion of
      critical path issues for a given clinical case, should be further explored and
      refined before transitioning to clinical trials. Future studies should
      investigate periodontal regenerative procedures in animal models, including
      rodents, in which the defects generated are designed to more accurately reflect
      the inflammatory status of the host and the shift in their pathogenic microflora.

PMID- 24744396
TI  - Successful Resuscitation With Intralipid After Marcaine Overdose.
AB  - The authors present the case of a 32-year-old woman who underwent concomitant
      abdominoplasty and mastopexy. Before discharge from the recovery room, she
      experienced cardiac arrest and seizures resulting from an accidental overdose of
      Marcaine, caused by failure of an intramuscular pain pump. The anesthesiologist
      initiated a rescue protocol with an Intralipid 20% bolus (1.5 mg/kg), followed by
      continuous intravenous infusion of 0.25 mg/kg for 60 minutes. The Intralipid
      intervention resulted in a successful outcome. This case emphasizes the
      importance of ensuring the availability of Intralipid 20% infusion in the
      operating room. Plastic surgeons who place postoperative pain pumps must be aware
      of this method of resuscitation and its effectiveness in treating possible cases
      of local anesthetic overdose or toxicity. LEVEL OF EVIDENCE: 5.

PMID- 24744397
TI  - A Structured End-of-Life Curriculum for Neonatal-Perinatal Postdoctoral Fellows.
AB  - Death in tertiary care neonatal intensive care units is a common occurrence.
      Despite recent advances in pediatric palliative education, evidence indicates
      that physicians are poorly prepared to care for dying infants and their families.
      Numerous organizations recommend increased training in palliative and end-of-life
      care for pediatric physicians. The purpose of this study is to develop a
      structured end-of-life curriculum for neonatal-perinatal postdoctoral fellows
      based on previously established principles and curricular guidelines on end-of
      life care in the pediatric setting. Results demonstrate statistically significant
      curriculum effectiveness in increasing fellow knowledge regarding patient
      qualification for comfort care and withdrawal of support (P = .03). Although not
      statistically significant, results suggest the curriculum may have improved
      fellows' knowledge of appropriate end-of-life medical management, comfort with
      addressing the family, and patient pain assessment and control.

PMID- 24744398
TI  - Chronic Pain and Risk Factors for Opioid Misuse in a Palliative Care Clinic.
AB  - OBJECTIVES: To describe the prevalence of chronic pain and the risk of opioid
      misuse in a palliative care clinic. METHODS: We reviewed patient records for 6
      months for source of pain, treatment status, opioid misuse risk (Cut down,
      Annoyed, Guilty, and Eye-opener [CAGE] and Screener and Opioid Assessment for
      Patients with Pain version 1.0-Short Form [SOAPP-SF] scores), and urine drug
      screens. RESULTS: Of 323 patients, 91% had cancer, 56% undergoing cancer
      treatment, while 28% had no evidence of disease. Eighty-six (27%) patients had
      noncancer pain. In all, 46% of new patients had positive scores on the SOAPP-SF
      and 15% had a positive CAGE. Of the less than 5% of visits that included a urine
      drug screen, 56% had aberrant results. CONCLUSION: Chronic pain and indicators of
      opioid misuse risk were prevalent. Outpatient palliative care practices should
      develop policies to address these issues.

PMID- 24744399
TI  - Reaction to Caregiving by Hospice Caregivers Upon Enrollment.
AB  - Significant research exists demonstrating the challenges faced by informal family
      caregivers as they care for their loved ones. How caregivers react to this
      experience, especially in the case of a terminal illness, is less understood.
      This study explores the reactions of hospice caregivers to their caregiving
      experience prior to enrollment in hospice and identifies potential stressors
      associated with those reactions. Results found anxiety to be a significant
      predictor in the reaction of caregivers to their caregiving experience upon
      hospice enrollment. 

PMID- 24744400
TI  - Increased expression of astrocyte markers in schizophrenia: Association with
      neuroinflammation.
AB  - OBJECTIVE: While schizophrenia may have a progressive component, the evidence for
      neurodegenerative processes as indicated by reactive astrocytes is inconclusive.
      We recently identified a subgroup of individuals with schizophrenia with
      increased expression of inflammatory markers in prefrontal cortex, and
      hypothesized that this subgroup would also have reactive astrocytes. METHOD: We
      measured glial fibrillary acidic protein (GFAP) mRNA by quantitative real-time
      reverse transcriptase polymerase chain reaction (RT-PCR) and protein levels by
      immunoblotting in grey matter homogenate from 37 individuals with schizophrenia
      and 37 unaffected controls. We examined the morphology of GFAP-positive
      astrocytes in immunostained sections of middle frontal gyrus. We tested if GFAP
      expression or astrocyte morphology were altered in people with schizophrenia with
      increased expression of inflammatory markers. We used RNA-Seq data on a subset of
      patients and controls (n=20/group) to ascertain whether mRNA transcripts
      associated with astrogliosis were elevated in the individuals with active
      neuroinflammation. RESULTS: GFAP (mRNA and protein) levels and astrocyte
      morphology were not significantly different between people with schizophrenia and
      controls overall. However, individuals with schizophrenia with neuroinflammation
      had increased expression of GFAP mRNA (t(33)=2.978, p=0.005), hypertrophic
      astrocyte morphology (chi(2)(2)=6.281, p=0.043), and statistically significant
      elevated expression of three mRNA transcripts previously associated with
      astrogliosis. CONCLUSIONS: We found clear evidence of astrogliosis in a subset of
      people with schizophrenia. We suggest that the lack of astrogliosis reported in
      previous studies may be due to cohort differences in aetiopathology, illness
      stage, treatment exposure, or a failure to examine subsets of people with
      schizophrenia.

PMID- 24744401
TI  - Photo quiz: heart transplant patient with knee drainage. Answer: Alternaria spp.

PMID- 24744402
TI  - Inconclusive reverse transcription-PCR assay comparison for dengue virus
      detection and serotyping.

PMID- 24744403
TI  - Reply to "Inconclusive reverse transcription-PCR assay comparison for dengue
      virus detection and serotyping".

PMID- 24744404
TI  - No evidence for contamination of Borrelia blood cultures: a review of facts.

PMID- 24744405
TI  - Reply to "No evidence for contamination of Borrelia blood cultures: a review of
      facts".

PMID- 24744406
TI  - Technical notes on the correct configuration of the Alfred 60/AST device for the
      detection of urinary tract infections.

PMID- 24744407
TI  - Reply to "Technical notes on the correct configuration of the Alfred 60/AST
      device for the detection of urinary tract infections".

PMID- 24744412
TI  - Association of paternal IQ in early adulthood with offspring mortality and
      hospital admissions for injuries: a cohort study of 503 492 Swedish children.
AB  - BACKGROUND: Higher intelligence (IQ) has been related to a lower risk of
      mortality and hospital admissions for injuries, but little is known about the
      effect of parental IQ on offspring outcomes. We explored associations of paternal
      IQ with mortality and hospitalisations for injuries from all external causes in
      offspring. METHODS: A cohort of 503 492 Swedish children under 5 years of age
      with information on paternal IQ was obtained by record linkage of national
      registers. HR with 95% CIs were estimated using Cox regression. RESULTS: There
      was some evidence that paternal IQ was inversely associated with total and
      external-cause mortality in offspring, although the effects were modest and
      disappeared when controlling for parents' socioeconomic position (SEP). The only
      robust gradient was found between paternal IQ and hospital admissions for
      injuries (HRper 1-SD increase in IQ 0.93, 95% CI 0.92 to 0.94; p<0.001), which
      was slightly attenuated but retained statistical significance after adjustment
      for SEP (0.95, 95% CI 0.94 to 0.97; p<0.001). CONCLUSIONS: Children to fathers
      with lower IQ may have an increased risk of injury by external causes. Messages
      on family safety and injury prevention might be tailored according to parental
      cognitive abilities.

PMID- 24744414
TI  - Level locomotion in wood ants: evidence for grounded running.
AB  - In order to better understand the strategies of locomotion in small insects, we
      have studied continuous level locomotion of the wood ant species Formica
      polyctena. We determined the three-dimensional centre of mass kinematics during
      the gait cycle and recorded the ground reaction forces of single legs utilising a
      self-developed test site. Our findings show that the animals used the same gait
      dynamics across a wide speed range without dissolving the tripodal stride
      pattern. To achieve higher velocities, the ants proportionally increased stride
      length and stepping frequency. The centre of mass energetics indicated a bouncing
      gait, in which horizontal kinetic and gravitational potential energy fluctuated
      in close phase. We determined a high degree of compliance especially in the front
      legs, as the effective leg length was nearly halved during the contact phase.
      This leads to only small vertical oscillations of the body, which are important
      in maintaining ground contact. Bouncing gaits without aerial phases seem to be a
      common strategy in small runners and can be sufficiently described by the bipedal
      spring-loaded inverted pendulum model. Thus, with our results, we provide
      evidence that wood ants perform 'grounded running'. 

PMID- 24744415
TI  - Osmoregulation in the Hawaiian anchialine shrimp Halocaridina rubra (Crustacea:
      Atyidae): expression of ion transporters, mitochondria-rich cell proliferation
      and hemolymph osmolality during salinity transfers.
AB  - Studies of euryhaline crustaceans have identified conserved osmoregulatory
      adaptions allowing hyper-osmoregulation in dilute waters. However, previous
      studies have mainly examined decapod brachyurans with marine ancestries
      inhabiting estuaries or tidal creeks on a seasonal basis. Here, we describe
      osmoregulation in the atyid Halocaridina rubra, an endemic Hawaiian shrimp of
      freshwater ancestry from the islands' anchialine ecosystem (coastal ponds with
      subsurface freshwater and seawater connections) that encounters near-continuous
      spatial and temporal salinity changes. Given this, survival and osmoregulatory
      responses were examined over a wide salinity range. In the laboratory, H. rubra
      tolerated salinities of ~0-560/00, acting as both a hyper- and hypo-osmoregulator
      and maintaining a maximum osmotic gradient of ~868 mOsm kg(-1) H2O in freshwater.
      Furthermore, hemolymph osmolality was more stable during salinity transfers
      relative to other crustaceans. Silver nitrate and vital mitochondria-rich cell
      staining suggest all gills are osmoregulatory, with a large proportion of each
      individual gill functioning in ion transport (including when H. rubra acts as an
      osmoconformer in seawater). Additionally, expression of ion transporters and
      supporting enzymes that typically undergo upregulation during salinity transfer
      in osmoregulatory gills (i.e. Na(+)/K(+)-ATPase, carbonic anhydrase,
      Na(+)/K(+)/2Cl(-) cotransporter, V-type H(+)-ATPase and arginine kinase) were
      generally unaltered in H. rubra during similar transfers. These results suggest
      H. rubra (and possibly other anchialine species) maintains high, constitutive
      levels of gene expression and ion transport capability in the gills as a means of
      potentially coping with the fluctuating salinities that are encountered in
      anchialine habitats. Thus, anchialine taxa represent an interesting avenue for
      future physiological research. 

PMID- 24744416
TI  - Lateral line analogue aids vision in successful predator evasion for the brief
      squid, Lolliguncula brevis.
AB  - Cephalopods have visual and mechanoreception systems that may be employed to
      sense and respond to an approaching predator. While vision presumably plays the
      dominant role, the importance of the lateral line analogue for predator evasion
      has not been examined in cephalopods. To test the respective roles of vision and
      the lateral line analogue, brief squid, Lolliguncula brevis, were observed in the
      presence of summer flounder, Paralichthys dentatus, under light and dark
      conditions with their lateral line analogue intact and ablated. Hair cell
      ablation was achieved through a pharmacological technique used for the first time
      on a cephalopod. The proportion of predator-prey interactions survived was
      significantly higher in the light non-ablated and light ablated groups compared
      with the dark ablated group. The mean number of interactions survived varied
      across treatment groups with the light non-ablated group having significantly
      more success than the light ablated, dark non-ablated and dark ablated groups.
      These findings demonstrate that although vision is the primary sense, the lateral
      line analogue also contributes to predator evasion in squid.

PMID- 24744418
TI  - Feather corticosterone reveals developmental stress in seabirds.
AB  - In nest-bound avian offspring, food shortages typically trigger a release of the
      stress hormone corticosterone (CORT). Recent studies indicate that CORT is
      passively deposited in the tissue of growing feathers and thus may provide an
      integrated measure of stress incurred during development in the nest. The current
      hypothesis predicts that, assuming a constant rate of feather growth, elevated
      CORT circulating in the blood corresponds to higher levels of CORT in feather
      tissue, but experimental evidence for nutritionally stressed chicks is lacking.
      Here, we examined how food limitation affects feather CORT content in the
      rhinoceros auklet (Cerorhinca moncerata). We (i) used captive chicks reared on
      control versus restricted diets, and (ii) applied this technique to free-living
      chicks with unknown nutritional histories that fledged at three separate
      colonies. We found that (i) feather growth was not affected by experimentally
      induced nutritional stress; (ii) captive chicks raised on a restricted diet had
      higher levels of CORT in their primary feathers; (iii) feather CORT deposition is
      a sensitive method of detecting nutritional stress; and (iv) free-living
      fledglings from the colony with poor reproductive performance had higher CORT in
      their primary feathers. We conclude that feather CORT is a sensitive integrated
      measure revealing the temporal dynamics of food limitations experienced by
      rhinoceros auklet nestlings. The use of feather CORT may be a powerful endocrine
      tool in ecological and evolutionary studies of bird species with similar
      preferential allocation of limited resources to feather development. 

PMID- 24744417
TI  - Reproductive status, endocrine physiology and chemical signaling in the
      Neotropical, swarm-founding eusocial wasp Polybia micans.
AB  - In the evolution of caste-based societies in Hymenoptera, the classical insect
      hormones juvenile hormone (JH) and ecdysteroids were co-opted into new functions.
      Social wasps, which show all levels of sociality and lifestyles, are an ideal
      group in which to study such functional changes. Virtually all studies on the
      physiological mechanisms underlying reproductive division of labor and caste
      functions in wasps have been done on independent-founding paper wasps, and the
      majority of these studies have focused on species specially adapted for
      overwintering. The relatively little-studied tropical swarm-founding wasps of the
      Epiponini (Vespidae) are a diverse group of permanently social wasps, with some
      species maintaining caste flexibility well into the adult phase. We investigated
      the behavior, reproductive status, JH and ecdysteroid titers in hemolymph,
      ecdysteroid content of the ovary and cuticular hydrocarbon (CHC) profiles in the
      caste-monomorphic, epiponine wasp Polybia micans Ducke. We found that the JH
      titer was not elevated in competing queens from established multiple-queen nests,
      but increased in lone queens that lack direct competition. In queenless colonies,
      JH titer rose transiently in young potential reproductives upon challenge by
      nestmates, suggesting that JH may prime the ovaries for further development.
      Ovarian ecdysteroids were very low in workers but higher and correlated with the
      number of vitellogenic oocytes in the queens. Hemolymph ecdysteroid levels were
      low and variable in both workers and queens. Profiles of P. micans CHCs reflected
      caste, age and reproductive status, but were not tightly linked to either
      hormone. These findings show a significant divergence in hormone function in
      swarm-founding wasps compared with independently founding ones. 

PMID- 24744419
TI  - Fifty years of J. R. Platt's strong inference.

PMID- 24744420
TI  - A unique mode of tissue oxygenation and the adaptive radiation of teleost fishes.
AB  - Teleost fishes constitute 95% of extant aquatic vertebrates, and we suggest that
      this is related in part to their unique mode of tissue oxygenation. We propose
      the following sequence of events in the evolution of their oxygen delivery
      system. First, loss of plasma-accessible carbonic anhydrase (CA) in the gill and
      venous circulations slowed the Jacobs-Stewart cycle and the transfer of acid
      between the plasma and the red blood cells (RBCs). This ameliorated the effects
      of a generalised acidosis (associated with an increased capacity for burst
      swimming) on haemoglobin (Hb)-O2 binding. Because RBC pH was uncoupled from
      plasma pH, the importance of Hb as a buffer was reduced. The decrease in
      buffering was mediated by a reduction in the number of histidine residues on the
      Hb molecule and resulted in enhanced coupling of O2 and CO2 transfer through the
      RBCs. In the absence of plasma CA, nearly all plasma bicarbonate ultimately
      dehydrated to CO2 occurred via the RBCs, and chloride/bicarbonate exchange was
      the rate-limiting step in CO2 excretion. This pattern of CO2 excretion across the
      gills resulted in disequilibrium states for CO2 hydration/dehydration reactions
      and thus elevated arterial and venous plasma bicarbonate levels. Plasma
      accessible CA embedded in arterial endothelia was retained, which eliminated the
      localized bicarbonate disequilibrium forming CO2 that then moved into the RBCs.
      Consequently, RBC pH decreased which, in conjunction with pH-sensitive Bohr/Root
      Hbs, elevated arterial oxygen tensions and thus enhanced tissue oxygenation.
      Counter-current arrangement of capillaries (retia) at the eye and later the swim
      bladder evolved along with the gas gland at the swim bladder. Both arrangements
      enhanced and magnified CO2 and acid production and, therefore, oxygen secretion
      to those specialised tissues. The evolution of beta-adrenergically stimulated RBC
      Na(+)/H(+) exchange protected gill O2 uptake during stress and further augmented
      plasma disequilibrium states for CO2 hydration/dehydration. Finally, RBC
      organophosphates (e.g. NTP) could be reduced during hypoxia to further increase
      Hb-O2 affinity without compromising tissue O2 delivery because high-affinity Hbs
      could still adequately deliver O2 to the tissues via Bohr/Root shifts. We suggest
      that the evolution of this unique mode of tissue O2 transfer evolved in the
      Triassic/Jurassic Period, when O2 levels were low, ultimately giving rise to the
      most extensive adaptive radiation of extant vertebrates, the teleost fishes. 

PMID- 24744421
TI  - Evidence for vocal learning in juvenile male killer whales, Orcinus orca, from an
      adventitious cross-socializing experiment.
AB  - Killer whales (Orcinus orca) are thought to learn their vocal dialect. Dispersal
      in the species is rare, but effects of shifts in social association on the
      dialect can be studied under controlled conditions. Individual call repertoires
      and social association were measured in three adult female killer whales and
      three males (two juveniles and an adult) during two periods, 2001-2003 and 2005
      2006. Three distinct dialect repertoires were represented among the subjects. An
      adventitious experiment in social change resulted from the birth of a calf and
      the transfer of two non-focal subjects in 2004. Across the two periods, 1691
      calls were collected, categorized and attributed to individuals. Repertoire
      overlap for each subject dyad was compared with an index of association. During
      2005-2006, the two juvenile males increased association with the unrelated adult
      male. By the end of the period, both had begun producing novel calls and call
      features characteristic of his repertoire. However, there was little or no
      reciprocal change and the adult females did not acquire his calls. Repertoire
      overlap and association were significantly correlated in the first period. In the
      second, median association time and repertoire similarity increased, but the
      relationship was only marginally significant. The results provided evidence that
      juvenile male killer whales are capable of learning new call types, possibly
      stimulated by a change in social association. The pattern of learning was
      consistent with a selective convergence of male repertoires. 

PMID- 24744422
TI  - Spontaneous unraveling of hagfish slime thread skeins is mediated by a seawater
      soluble protein adhesive.
AB  - Hagfishes are known for their ability to rapidly produce vast quantities of slime
      when provoked. The slime is formed via the interaction between seawater and two
      components released by the slime glands: mucin vesicles from gland mucous cells,
      which swell and rupture in seawater to form a network of mucus strands, and
      intermediate filament-rich threads, which are produced within gland thread cells
      as tightly coiled bundles called skeins. A previous study showed that the
      unraveling of skeins from Atlantic hagfish (Myxine glutinosa) requires both the
      presence of mucins and hydrodynamic mixing. In contrast, skeins from Pacific
      hagfish (Eptatretus stoutii) unravel in the absence of both mucins and mixing. We
      tested the hypothesis that spontaneous unraveling of E. stoutii skeins is
      triggered by the dissolution of a seawater-soluble protein adhesive and the
      release of stored strain energy within the coiled thread. Here we show that, as
      predicted by this hypothesis, unraveling can be initiated by a protease under
      conditions in which unraveling does not normally occur. We also demonstrate,
      using high resolution scanning electron microscopy, that the treatment of skeins
      with solutions that cause unraveling also leads to the disappearance of surface
      and inter-thread features that remain when skeins are washed with stabilizing
      solutions. Our study provides a mechanism for the deployment of thread skeins in
      Pacific hagfish slime, and raises the possibility of producing novel biomimetic
      protein adhesives that are salt, temperature and kosmotrope sensitive. 

PMID- 24744423
TI  - Characterisation of putative oxygen chemoreceptors in bowfin (Amia calva).
AB  - Serotonin containing neuroepithelial cells (NECs) are putative oxygen sensing
      cells found in different locations within the gills of fish. In this study we
      wished to determine the effect of sustained internal (blood) hypoxaemia versus
      external (aquatic) hypoxia on the size and density of NECs in the first gill arch
      of bowfin (Amia calva), a facultative air breather. We identified five different
      populations of serotonergic NECs in this species (Types I-V) based on location,
      presence of synaptic vesicles (SV) that stain for the antibody SV2, innervation
      and labelling with the neural crest marker HNK-1. Cell Types I-III were
      innervated, and these cells, which participate in central O2 chemoreflexes, were
      studied further. Although there was no change in the density of any cell type in
      bowfin after exposure to sustained hypoxia (6.0 kPa for 7 days) without access to
      air, all three of these cell types increased in size. In contrast, only Type II
      and III cells increased in size in bowfin exposed to sustained hypoxia with
      access to air. These data support the suggestion that NECs are putative oxygen
      sensing cells, that they occur in several locations, and that Type I cells
      monitor only hypoxaemia, whereas both other cell types monitor hypoxia and
      hypoxaemia. 

PMID- 24744424
TI  - Why do insects enter and recover from chill coma? Low temperature and high
      extracellular potassium compromise muscle function in Locusta migratoria.
AB  - When exposed to low temperatures, many insect species enter a reversible comatose
      state (chill coma), which is driven by a failure of neuromuscular function. Chill
      coma and chill coma recovery have been associated with a loss and recovery of ion
      homeostasis (particularly extracellular [K(+)], [K(+)]o) and accordingly onset of
      chill coma has been hypothesized to result from depolarization of membrane
      potential caused by loss of ion homeostasis. Here, we examined whether onset of
      chill coma is associated with a disturbance in ion balance by examining the
      correlation between disruption of ion homeostasis and onset of chill coma in
      locusts exposed to cold at varying rates of cooling. Chill coma onset temperature
      changed maximally 1 degrees C under different cooling rates and marked
      disturbances of ion homeostasis were not observed at any of the cooling rates. In
      a second set of experiments, we used isolated tibial muscle to determine how
      temperature and [K(+)]o, independently and together, affect tetanic force
      production. Tetanic force decreased by 80% when temperature was reduced from 23
      degrees C to 0.5 degrees C, while an increase in [K(+)]o from 10 mmol l(-1) to 30
      mmol l(-1) at 23 degrees C caused a 40% reduction in force. Combining these two
      stressors almost abolished force production. Thus, low temperature alone may be
      responsible for chill coma entry, rather than a disruption of extracellular K(+)
      homeostasis. As [K(+)] also has a large effect on tetanic force production, it is
      hypothesized that recovery of [K(+)]o following chill coma could be important for
      the time to recovery of normal neuromuscular function. 

PMID- 24744425
TI  - Social attraction mediated by fruit flies' microbiome.
AB  - Larval and adult fruit flies are attracted to volatiles emanating from food
      substrates that have been occupied by larvae. We tested whether such volatiles
      are emitted by the larval gut bacteria by conducting tests under bacteria-free
      (axenic) conditions. We also tested attraction to two bacteria species,
      Lactobacillus brevis, which we cultured from larvae in our lab, and L. plantarum,
      a common constituent of fruit flies' microbiome in other laboratory populations
      and in wild fruit flies. Neither larvae nor adults showed attraction to axenic
      food that had been occupied by axenic larvae, but both showed the previously
      reported attraction to standard food that had been occupied by larvae with an
      intact microbiome. Larvae also showed significant attraction to volatiles from
      axenic food and larvae to which we added only either L. brevis or L. plantarum,
      and volatiles from L. brevis reared on its optimal growth medium. Controlled
      learning experiments indicated that larvae experienced with both standard and
      axenic used food do not perceive either as superior, while focal larvae
      experienced with simulated used food, which contains burrows, perceive it as
      superior to unused food. Our results suggest that flies rely on microbiome
      derived volatiles for long-distance attraction to suitable food patches. Under
      natural settings, fruits often contain harmful fungi and bacteria, and both L.
      brevis and L. plantarum produce compounds that suppress the growth of some
      antagonistic fungi and bacteria. The larval microbiome volatiles may therefore
      lead prospective fruit flies towards substrates with a hospitable microbial
      environment. 

PMID- 24744427
TI  - Transposable elements, a treasure trove to decipher epigenetic variation:
      insights from Arabidopsis and crop epigenomes.
AB  - In the past decade, plant biologists and breeders have developed a growing
      interest in the field of epigenetics, which is defined as the study of heritable
      changes in gene expression that cannot be explained by changes in the DNA
      sequence. Epigenetic marks can be responsive to the environment, and evolve
      faster than genetic changes. Therefore, epigenetic diversity may represent an
      unexplored resource of natural variation that could be used in plant breeding
      programmes. On the other hand, crop genomes are largely populated with
      transposable elements (TEs) that are efficiently targeted by epigenetic marks,
      and part of the epigenetic diversity observed might be explained by TE
      polymorphisms. Characterizing the degree to which TEs influence epigenetic
      variation in crops is therefore a major goal to better use epigenetic variation.
      To date, epigenetic analyses have been mainly focused on the model plant
      Arabidopsis thaliana, and have provided clues on epigenome features, components
      that silence pathways, and effects of silencing impairment. But to what extent
      can Arabidopsis be used as a model for the epigenomics of crops? In this review,
      we discuss the similarities and differences between the epigenomes of Arabidopsis
      and crops. We explore the relationship between TEs and epigenomes, focusing on TE
      silencing control and escape, and the impact of TE mobility on epigenomic
      variation. Finally, we provide insights into challenges to tackle, and future
      directions to take in the route towards using epigenetic diversity in plant
      breeding programmes.

PMID- 24744428
TI  - Arabidopsis floral phytomer development: auxin response relative to biphasic
      modes of organ initiation.
AB  - In the Arabidopsis inflorescence meristem (IM), auxin is considered a
      prepatterning signal for floral primordia, whereas a centripetal mode of
      positional information for floral organ identity is inherent to the ABCE model.
      However, spatio-temporal patterns of organ initiation in each whorl at the
      earliest initiation stages are largely unknown. Evidence suggests that initial
      flower development occurs along an abaxial/adaxial axis and conforms to phytomer
      theory. Use of the founder cell marker DORNROSCHEN-LIKE (DRNL) as a tool in
      leafy, puchi, and apetala 1 cauliflower mutant backgrounds suggests that bract
      founder cells are marked at the IM periphery. The DRNL transcription domain in
      the wild-type IM is spatially discrete from DR5 expression, suggesting that bract
      initiation is independent of canonical auxin response. When bracts develop in lfy
      and puchi mutant floral primordia the initiation of lateral sepals precedes the
      specification of medial sepals compared with wild type, showing an interplay
      between bract and abaxial sepal founder cell recruitment. In the perianthia (pan)
      mutant background, DRNL expression indicates that a radial outer whorl
      arrangement derives from splitting of sepal founder cell populations at abaxial
      and adaxial positions. This splitting of incipient sepal primordia is partially
      dependent on PRESSED FLOWER (PRS) activity and implies that sepal specification
      is independent of WUSCHEL and CLAVATA3 expression, as both marker genes only
      regain activity in stage-2 flowers, when patterning of inner floral organs
      switches to a centripetal mode. The transition from an initially abaxial/adaxial
      into a centripetal patterning programme, and its timing represent an adaptive
      trait that possibly contributes to variation in floral morphology, especially
      unidirectional organ initiation. 

PMID- 24744429
TI  - The AP2/ERF transcription factor SlERF52 functions in flower pedicel abscission
      in tomato.
AB  - In plants, abscission removes senescent, injured, infected, or dispensable
      organs. Induced by auxin depletion and an ethylene burst, abscission requires
      pronounced changes in gene expression, including genes for cell separation
      enzymes and regulators of signal transduction and transcription. However, the
      understanding of the molecular basis of this regulation remains incomplete. To
      examine gene regulation in abscission, this study examined an ERF family
      transcription factor, tomato (Solanum lycopersicum) ETHYLENE-RESPONSIVE FACTOR 52
      (SlERF52). SlERF52 is specifically expressed in pedicel abscission zones (AZs)
      and SlERF52 expression is suppressed in plants with impaired function of
      MACROCALYX and JOINTLESS, which regulate pedicel AZ development. RNA interference
      was used to knock down SlERF52 expression to show that SlERF52 functions in
      flower pedicel abscission. When treated with an abscission-inducing stimulus, the
      SlERF52-suppressed plants showed a significant delay in flower abscission
      compared with wild type. They also showed reduced upregulation of the genes for
      the abscission-associated enzymes cellulase and polygalacturonase. SlERF52
      suppression also affected gene expression before the abscission stimulus,
      inhibiting the expression of pedicel AZ-specific transcription factor genes, such
      as the tomato WUSCHEL homologue, GOBLET, and Lateral suppressor, which may
      regulate meristematic activities in pedicel AZs. These results suggest that
      SlERF52 plays a pivotal role in transcriptional regulation in pedicel AZs at both
      pre-abscission and abscission stages. 

PMID- 24744430
TI  - Involvement of reactive oxygen species in endosperm cap weakening and embryo
      elongation growth during lettuce seed germination.
AB  - Endosperm cap (CAP) weakening and embryo elongation growth are prerequisites for
      the completion of lettuce seed germination. Although it has been proposed that
      the cell wall loosening underlying these processes results from an enzymatic
      mechanism, it is still unclear which enzymes are involved. Here it is shown that
      reactive oxygen species (ROS), which are non-enzymatic factors, may be involved
      in the two processes. In Guasihong lettuce seeds imbibed in water, O2.(-) and
      H2O2 accumulated and peroxidase activity increased in the CAP, whereas its
      puncture force decreased. In addition, in the radicle, the increase in embryo
      growth potential was accompanied by accumulation of O2.(-) and an increase in
      peroxidase activity. Imbibing seeds in 0.3% sodium dichloroisocyanurate (SDIC)
      reduced endosperm viability and the levels of O2.(-), H2O2, and peroxidase
      activity in the CAP, whereas the decrease in its puncture force was inhibited.
      However, in the embryo, SDIC did not affect the accumulation of O2.(-),
      peroxidase activity, and the embryo growth potential. As a result, SDIC caused
      atypical germination, in which the endosperm ruptured at the boundary between the
      CAP and lateral endosperm. ROS scavengers and ROS generation inhibitors inhibited
      the CAP weakening and also decreased the embryo growth potential, thus decreasing
      the percentage of seed germination. Exogenous ROS and ROS generation inducers
      increased the percentage of CAP rupture to some extent, and the addition of H2O2
      to 0.3% SDIC enabled some seeds to undergo typical germination. 

PMID- 24744431
TI  - Light to liquid fuel: theoretical and realized energy conversion efficiency of
      plants using crassulacean acid metabolism (CAM) in arid conditions.
AB  - There has been little attention paid to crassulacean acid metabolism (CAM) as a
      mechanism for bioenergy crop tolerance to water limitation, in part, because
      potential yields of CAM plants have been assumed to be lower than those of most
      commonly studied bioenergy crops. The photochemical efficiency, water-use
      efficiency (WUE), biomass production, and fuel yield potentials of CAM, C3, and
      C4 plants that are considered or already in use for bioenergy are reviewed here.
      The theoretical photosynthetic efficiency of CAM plants can be similar to or
      greater than other photosynthetic pathways. In arid conditions, the greater WUE
      of CAM species results in theoretical biomass yield potentials that are 147%
      greater than C4 species. The realized yields of CAM plants are similar to the
      theoretical yields that account for water-limiting conditions. CAM plants can
      potentially be viable commercial bioenergy crops, but additional direct yield
      measurements from field trials of CAM species are still needed.

PMID- 24744432
TI  - Mapping and Expression of Candidate Genes for Development Rate in Rainbow Trout
      (Oncorhynchus mykiss).
AB  - Development rate has important implications for individual fitness and
      physiology. In salmonid fishes, development rate correlates with many traits
      later in life, including life-history diversity, growth, and age and size at
      sexual maturation. In rainbow trout (Oncorhynchus mykiss), a quantitative trait
      locus for embryonic development rate has been detected on chromosome 5 across
      populations. However, few candidate genes have been identified within this
      region. In this study, we use gene mapping, gene expression, and quantitative
      genetic methods to further identify the genetic basis of embryonic developmental
      rate in O. mykiss Among the genes located in the region of the major development
      rate quantitative trait locus (GHR1, Clock1a, Myd118-1, and their paralogs), all
      were expressed early in embryonic development (fertilization through hatch), but
      none were differentially expressed between individuals with the fast- or slow
      developing alleles for a major embryonic development rate quantitative trait
      locus. In a follow-up study of migratory and resident rainbow trout from natural
      populations in Alaska, we found significant additive variation in development
      rate and, moreover, found associations between development rate and allelic
      variation in all 3 candidate genes within the quantitative trait locus for
      embryonic development. The mapping of these genes to this region and associations
      in multiple populations provide positional candidates for further study of their
      roles in growth, development, and life-history diversity in this model salmonid.

PMID- 24744433
TI  - IL-17+Foxp3+ T cells: an intermediate differentiation stage between Th17 cells
      and regulatory T cells.
AB  - Foxp3(+) Tregs have been known as a major regulator of immune homeostasis through
      their immunosuppressive function. Th17 lineage is a CD4(+) T cell subset that
      exerts its function by secreting proinflammatory cytokines and protecting host
      against microbial infections. The altered ratio between Foxp3(+) Tregs and Th17
      cells plays an important role in the pathogenesis of immune-related diseases.
      Recent mice and human studies have demonstrated that Tregs can be reprogrammed
      into a novel population, IL-17(+)Foxp3(+) T cells, phenotypically and
      functionally resembling Th17 cells under the complicated cytokine stimulation.
      The identification of IL-17(+)Foxp3(+) T cells may provide a new understanding of
      therapy targeting Tregs and Th17 cells in autoimmune diseases and cancer. Here,
      we highlight significant data regarding the phenotype profile, origination,
      differentiation, and the pleiotropic functions of IL-17(+)Foxp3(+) T cells and
      the reciprocal relationships of these cells to Tregs and Th17 cells. Furthermore,
      the role of IL-17(+)Foxp3(+) T cells in tumorigenesis and clinical implications
      in cancer therapy are discussed in this review. 

PMID- 24744434
TI  - Delta9-Tetrahydrocannabinol-induced anti-inflammatory responses in adolescent
      mice switch to proinflammatory in adulthood.
AB  - Marijuana abuse is prominent among adolescents. Although Delta(9)-THC, one of its
      main components, has been demonstrated to modulate immunity in adults, little is
      known about its impact during adolescence on the immune system and the long
      lasting effects in adulthood. We demonstrate that 10 days of Delta(9)-THC
      treatment induced a similar alteration of macrophage and splenocyte cytokines in
      adolescent and adult mice. Immediately at the end of chronic Delta(9)-THC, a
      decrease of proinflammatory cytokines IL- 1beta and TNF-alpha and an increase of
      anti-inflammatory cytokine IL-10 production by macrophages were present as
      protein and mRNA in adolescent and adult mice. In splenocytes, Delta(9)-THC
      modulated Th1/Th2 cytokines skewing toward Th2: IFN-gamma was reduced, and IL-4
      and IL-10 increased. These effects were lost in adult animals, 47 days after the
      last administration. In contrast, in adult animals treated as adolescents, a
      perturbation of immune responses, although in an opposite direction, was present.
      In adults treated as adolescents, a proinflammatory macrophage phenotype was
      observed (IL-1beta and TNF-alpha were elevated; IL-10 decreased), and the
      production of Th cytokines was blunted. IgM titers were also reduced.
      Corticosterone concentrations indicate a long-lasting dysregulation of HPA in
      adolescent mice. We measured blood concentrations of Delta(9)-THC and its
      metabolites, showing that Delta(9)-THC plasma levels in our mice are in the order
      of those achieved in human heavy smokers. Our data demonstrate that Delta(9)-THC
      in adolescent mice triggers immune dysfunctions that last long after the end of
      abuse, switching the murine immune system to proinflammatory status in adulthood.

PMID- 24744435
TI  - A novel stop mutation in the vascular endothelial growth factor-C gene (VEGFC)
      results in Milroy-like disease.
AB  - BACKGROUND: Milroy and Milroy-like disease are rare disorders characterised by
      congenital lymphoedema caused by dysfunctional lymphatic vessel formation. Loss
      of extracellular response mediated by vascular endothelial growth factor receptor
      3 (VEGFR-3) is associated with Milroy disease, and VEGFR-3 gene is mutated in
      around 70% of the cases diagnosed. The only genetic alteration known to be
      associated with Milroy-like disease was recently identified in a family with a
      frameshift mutation in vascular endothelial growth factor C (VEGFC) gene, which
      encodes a VEGFR3 ligand. METHODS AND RESULTS: We report a newborn patient with an
      external phenotype consistent with Milroy disease and a truncating mutation
      (p.R210X) in the VEGFC gene detected by exome sequence analysis. Subsequent
      analysis, by lymphoscintigraphic scan, performed for research purposes, allowed
      us to correct the diagnosis, confirming patient's disease as Milroy-like. The
      mutation segregates with the phenotype in the family according to a dominant
      model with full penetrance. CONCLUSIONS: The clinical presentation, similar to
      Milroy disease, indicates an overlapping of the external phenotype of both
      diseases, suggesting that genetic analysis of VEGFC would be useful in diagnosing
      patients that present with Milroy features but have no mutation in VEGFR-3.
      Establishing a well-defined genetic pattern would help with differential
      diagnosis.

PMID- 24744436
TI  - Pathogenic mutations in GLI2 cause a specific phenotype that is distinct from
      holoprosencephaly.
AB  - BACKGROUND: Mutations in GLI2 have been associated with holoprosencephaly (HPE),
      a neuroanatomic anomaly resulting from incomplete cleavage of the developing
      forebrain, and an HPE-like phenotype involving pituitary anomalies and
      polydactyly. OBJECTIVE: To characterise the genotypic and phenotypic findings in
      individuals with GLI2 variants and clarify clinical findings in individuals with
      loss-of-function mutations. METHODS: Through the National Institutes of Health
      and collaborating centres, ~400 individuals with HPE spectrum disorders,
      endocrine disorders or craniofacial anomalies were screened for GLI2 mutations.
      Results were combined with all published cases. We compared the clinical and
      molecular features of individuals with truncating mutations to individuals with
      variants of unknown significance (defined as not resulting in protein truncation,
      reported in normal controls and/or deemed unlikely to be pathogenic by functional
      prediction software). RESULTS: 112 individuals with variants in GLI2 were
      identified, with 43 having truncating mutations. Individuals with truncating
      mutations were more likely to have both pituitary anomalies and polydactyly
      versus those with variants of unknown significance (p<0.0001 by Fisher's exact
      test); only 1 of 43 had frank HPE. These individuals were more likely to have
      recognised penetrance (polydactyly or pituitary anomalies or both) than those
      without truncating mutations (p=0.0036 by Fisher's exact test). A common facial
      phenotype was seen in individuals (with midface hypoplasia, cleft lip/palate and
      hypotelorism) with truncating mutations. CONCLUSIONS: Individuals with truncating
      mutations in GLI2 typically present with pituitary anomalies, polydactyly and
      subtle facial features rather than HPE. This will be helpful in screening
      populations for GLI2 mutations and for counselling affected patients. TRIAL
      REGISTRATION: 98-HG-0249/04-HG-0093.

PMID- 24744438
TI  - Cytomegalovirus-responsive gammadelta T cells: novel effector cells in antibody
      mediated kidney allograft microcirculation lesions.
AB  - Human cytomegalovirus infection in transplant recipients has been associated with
      adverse renal allograft outcome and with a large gammadelta T-cell response, but
      whether both mechanisms are connected is unknown. We previously showed that most
      expanded circulating cytomegalovirus-responsive gammadelta T cells express the
      Fcgamma-receptor CD16, suggesting that gammadelta T cells may participate in
      allograft lesions mediated by donor-specific antibodies through antibody
      dependent cellular cytotoxicity. Here, we show that cytomegalovirus-specific
      CD16(pos) gammadelta T cells can perform antibody-dependent cellular cytotoxicity
      against stromal cells coated with donor-specific antibodies in vitro. In vivo,
      graft-infiltrating gammadelta T cells localized in close contact with endothelial
      cells only in patients who experienced cytomegalovirus infection and were more
      frequent within peritubular capillaries and glomeruli from antibody-mediated
      acute rejections than within those from T cell-mediated acute rejections.
      Finally, a persistently increased percentage of circulating cytomegalovirus
      induced gammadelta T cells correlated inversely with the 1-year eGFR only in
      kidney recipients with donor-specific antibodies. Collectively, these data
      support the conclusion that cytomegalovirus-induced gammadelta T cells are
      involved in, and may serve as a clinical biomarker of, antibody-mediated lesions
      of kidney transplants. Moreover, these findings offer a new physiopathologic link
      between cytomegalovirus infection and allograft dysfunction in recipients with
      donor-specific antibodies. 

PMID- 24744439
TI  - Sonic hedgehog is a novel tubule-derived growth factor for interstitial
      fibroblasts after kidney injury.
AB  - Tubular epithelium constitutes the majority of the renal parenchyma and is the
      primary target of various kidney injuries. However, how the injured tubules drive
      interstitial fibroblast activation and proliferation remains poorly understood.
      Here, we investigated the role of sonic hedgehog (Shh), a secreted extracellular
      signaling protein, in fibroblast proliferation. Shh was induced in renal tubular
      epithelia in animal models of CKD induced by ischemia/reperfusion injury (IRI),
      adriamycin, or renal mass ablation, and in renal tubules of kidney biopsy
      specimens from CKD patients with different etiologies. Using Gli1-CreER(T2)
      reporter mice, we identified interstitial fibroblasts as the principal targets of
      renal Shh signaling in vivo. In vitro, incubation with Shh promoted normal rat
      kidney fibroblast proliferation, which was assessed by cell counting, MTT assay,
      and BrdU incorporation assay, and stimulated the induction of numerous
      proliferation-related genes. However, Shh had no effect on the proliferation of
      renal tubular epithelial cells. In vivo, overexpression of Shh promoted
      fibroblast expansion and aggravated kidney fibrotic lesions after IRI.
      Correspondingly, blockade of Shh signaling by cyclopamine, a small molecule
      inhibitor of Smoothened, inhibited fibroblast proliferation, reduced
      myofibroblast accumulation, and attenuated renal fibrosis. These studies identify
      Shh as a novel, specific, and potent tubule-derived growth factor that promotes
      interstitial fibroblast proliferation and activation. Our data also suggest that
      blockade of Shh signaling is a plausible strategy for therapeutic intervention of
      renal fibrosis. 

PMID- 24744440
TI  - Aldosterone regulates microRNAs in the cortical collecting duct to alter sodium
      transport.
AB  - A role for microRNAs (miRs) in the physiologic regulation of sodium transport in
      the kidney has not been established. In this study, we investigated the potential
      of aldosterone to alter miR expression in mouse cortical collecting duct (mCCD)
      epithelial cells. Microarray studies demonstrated the regulation of miR
      expression by aldosterone in both cultured mCCD and isolated primary distal
      nephron principal cells. Aldosterone regulation of the most significantly
      downregulated miRs, mmu-miR-335-3p, mmu-miR-290-5p, and mmu-miR-1983 was
      confirmed by quantitative RT-PCR. Reducing the expression of these miRs
      separately or in combination increased epithelial sodium channel (ENaC)-mediated
      sodium transport in mCCD cells, without mineralocorticoid supplementation.
      Artificially increasing the expression of these miRs by transfection with plasmid
      precursors or miR mimic constructs blunted aldosterone stimulation of ENaC
      transport. Using a newly developed computational approach, termed ComiR, we
      predicted potential gene targets for the aldosterone-regulated miRs and confirmed
      ankyrin 3 (Ank3) as a novel aldosterone and miR-regulated protein. A dual
      luciferase assay demonstrated direct binding of the miRs with the Ank3-3'
      untranslated region. Overexpression of Ank3 increased and depletion of Ank3
      decreased ENaC-mediated sodium transport in mCCD cells. These findings implicate
      miRs as intermediaries in aldosterone signaling in principal cells of the distal
      kidney nephron. 

PMID- 24744441
TI  - Prenatal risk factors for childhood CKD.
AB  - Development of CKD may be programmed prenatally. We sought to determine the
      association of childhood CKD with prenatal risk factors, including birth weight,
      maternal diabetes mellitus (DM), and maternal overweight/obesity. We conducted a
      population-based, case-control study with 1994 patients with childhood CKD (<21
      years of age at diagnosis) and 20,032 controls in Washington state. We linked
      maternal and infant characteristics in birth records from 1987 to 2008 to
      hospital discharge data and used logistic regression analysis to assess the
      association of prenatal risk factors with childhood CKD. The prevalence of CKD
      was 126.7 cases per 100,000 births. High birth weight and maternal pregestational
      DM associated nominally with CKD, with respective crude odds ratios (ORs) of 1.17
      (95% confidence interval [95% CI], 1.03 to 1.34) and 1.97 (95% CI, 1.15 to 3.37);
      however, adjustment for maternal confounders attenuated these associations to
      0.97 (95% CI, 0.79 to 1.21) and 1.19 (95% CI, 0.51 to 2.81), respectively. The
      adjusted ORs for CKD associated with other prenatal factors were 2.88 (95% CI,
      2.28 to 3.63) for low birth weight, 1.54 (95% CI, 1.13 to 2.09) for maternal
      gestational DM, 1.24 (95% CI, 1.05 to 1.48) for maternal overweight, and 1.26
      (95% CI, 1.05 to 1.52) for maternal obesity. In subgroup analysis by CKD subtype,
      low birth weight and maternal pregestational DM associated significantly with
      increased risk of renal dysplasia/aplasia. Low birth weight, maternal gestational
      DM, and maternal overweight/obesity associated significantly with obstructive
      uropathy. These data suggest that prenatal factors may impact the risk of CKD.
      Future studies should aim to determine if modification of these factors could
      reduce the risk of childhood CKD. 

PMID- 24744443
TI  - The neuropsychiatry of tinnitus: a circuit-based approach to the causes and
      treatments available.
AB  - Patients presenting with tinnitus commonly have neuropsychiatric symptoms with
      which physicians need to be familiar. We provide an overview of tinnitus,
      including its types and pathophysiology. We discuss how recent methods such as
      transcranial magnetic stimulation, positron emission tomography, MRI,
      magnetoencephalography and quantitative EEG improve our understanding of the
      pathophysiology of tinnitus and connect tinnitus to the neuropsychiatric
      symptoms. We then explain why treatment of the tinnitus patient falls within the
      purview of neuropsychiatry. Psychiatric problems such as depression, anxiety and
      personality disorders are discussed. We also discuss how stress, headache,
      cognitive processing speed and sleep disturbance are associated with tinnitus.
      Finally, we provide a brief overview of treatment options and discuss the
      efficacy of various medications, including benzodiazepines, antidepressants,
      antipsychotics and mood-stabilising agents, and various non-pharmacological
      treatment options, such as cognitive behavioural therapy, habituation therapy and
      acupuncture. We also discuss how brain stimulation therapies are being developed
      for the treatment of tinnitus. In conclusion, a review of the literature
      demonstrates the varied neuropsychiatric manifestations of tinnitus. Imaging
      studies help to explain the mechanism of the association. However, more research
      is needed to elucidate the neurocircuitry underlying the association. 

PMID- 24744442
TI  - Sall1 maintains nephron progenitors and nascent nephrons by acting as both an
      activator and a repressor.
AB  - The balanced self-renewal and differentiation of nephron progenitors are critical
      for kidney development and controlled, in part, by the transcription factor Six2,
      which antagonizes canonical Wnt signaling-mediated differentiation. A nuclear
      factor, Sall1, is expressed in Six2-positive progenitors as well as
      differentiating nascent nephrons, and it is essential for kidney formation.
      However, the molecular functions and targets of Sall1, especially the functions
      and targets in the nephron progenitors, remain unknown. Here, we report that
      Sall1 deletion in Six2-positive nephron progenitors results in severe progenitor
      depletion and apoptosis of the differentiating nephrons in mice. Analysis of mice
      with an inducible Sall1 deletion revealed that Sall1 activates genes expressed in
      progenitors while repressing genes expressed in differentiating nephrons. Sall1
      and Six2 co-occupied many progenitor-related gene loci, and Sall1 bound to Six2
      biochemically. In contrast, Sall1 did not bind to the Wnt4 locus suppressed by
      Six2. Sall1-mediated repression was also independent of its binding to DNA. Thus,
      Sall1 maintains nephron progenitors and their derivatives by a unique mechanism,
      which partly overlaps but is distinct from that of Six2: Sall1 activates
      progenitor-related genes in Six2-positive nephron progenitors and represses gene
      expression in Six2-negative differentiating nascent nephrons. 

PMID- 24744444
TI  - The glucose-dependent insulinotropic polypeptide receptor: a novel target for
      neuroendocrine tumor imaging-first preclinical studies.
AB  - A new family of peptide receptors, the incretin receptor family, overexpressed on
      many neuroendocrine tumors (NETs) is of great importance because it may enable
      the in vivo peptide-based receptor targeting of a category of NETs that does not
      express the somatostatin receptor. Impressive in vivo diagnostic data were
      published for glucagonlike peptide 1 receptor-targeting radiopeptides. Recently,
      promising in vitro data have appeared for the second member of the incretin
      family, the glucose-dependent insulinotropic polypeptide (GIP) receptor. This
      prompted us to develop and evaluate a new class of radioligands with the
      potential to be used for the in vivo targeting of GIP receptor-positive tumors.
      METHODS: GIP(1-42) was modified C-terminally, and the truncated peptides
      [Lys(30)(aminohexanoic acid [Ahx]-DOTA)]GIP(1-30)NH2 (EG1), [Lys(16)(Ahx
      DOTA)]GIP(1-30)NH2 (EG2), and [Nle(14), Lys(30)(Ahx-DOTA)]GIP(1-30)NH2 (EG4) were
      conjugated with Ahx-DOTA via the Lys(16) and Lys(30) side chains. Their
      inhibitory concentration of 50% (IC50) was determined using [(125)I-Tyr(10)]GIP(1
      30) as radioligand and GIP(1-30) as control peptide. The DOTA conjugates were
      labeled with (111)In and (68)Ga. In vitro evaluation included saturation and
      internalization studies using the pancreatic endocrine cell line INR1G9
      transfected with the human GIP receptor (INR1G9-hGIPr). The in vivo evaluation
      consisted of biodistribution and PET imaging studies on nude mice bearing INR1G9
      hGIPr tumors. RESULTS: Binding studies (IC50 and saturation studies) showed high
      affinity toward GIP receptor for the GIP conjugates. Specific in vitro
      internalization was found, and almost the entire cell-associated activity was
      internalized (>90% of the cell-bound activity), supporting the agonist potency of
      the (111)In-vectors. (111)In-EG4 and (68)Ga-EG4 were shown to specifically target
      INR1G9-hGIPr xenografts, with tumor uptake of 10.4% +/- 2.2% and 17.0% +/- 4.4%
      injected activity/g, 1 h after injection, respectively. Kidneys showed the
      highest uptake, which could be reduced by approximately 40%-50% with a modified
      fluid-gelatin plasma substitute or an inhibitor of the serine protease dipeptidyl
      peptidase 4. The PET images clearly visualized the tumor. CONCLUSION: The
      evaluation of EG4 as a proof-of-principle radioligand indicated the feasibility
      of imaging GIP receptor-positive tumors. These results prompt us to continue the
      development of this family of radioligands for imaging of a broad spectrum of
      NETs.

PMID- 24744445
TI  - Hepatobiliary scintigraphy in 2014.
AB  - Cholescintigraphy with (99m)Tc-hepatobiliary radiopharmaceuticals has been an
      important, clinically useful diagnostic imaging study for almost 4 decades. It
      continues to be in much clinical demand; however, the indications, methodology,
      and interpretative criteria have evolved over the years. This review will
      emphasize state-of-the-art methodology and diagnostic criteria for various
      clinical indications, including acute cholecystitis, chronic acalculous
      gallbladder disease, high-grade and partial biliary obstruction, and the
      postcholecystectomy pain syndrome, including sphincter-of-Oddi dysfunction and
      biliary atresia. The review will also emphasize the use of diagnostic
      pharmacologic interventions, particularly sincalide. 

PMID- 24744446
TI  - International guidelines for pediatric radiopharmaceutical administered
      activities.

PMID- 24744447
TI  - Preparation and Evaluation of (99m)Tc-Epidermal Growth Factor Receptor (EGFR)
      Peptide Nucleic Acid for Visualization of EGFR Messenger RNA Expression in
      Malignant Tumors.
AB  - Epidermal growth factor receptor (EGFR) is overexpressed in many carcinomas and
      remains a prime target for diagnostic and therapeutic applications. There is a
      need to develop noninvasive methods to identify the subset of patients that is
      most likely to benefit from EGFR-targeted treatment. Noninvasive imaging of EGFR
      messenger RNA (mRNA) expression may be a useful approach. The aim of this study
      was to develop a method for preparation of single-photon-emitting probes, (99m)Tc
      labeled EGFR mRNA antisense peptide nucleic acid (PNA) ((99m)Tc-EGFR-PNA), and
      nontargeting control ((99m)Tc-CTL-PNA) and to evaluate their feasibility for
      imaging EGFR mRNA overexpression in malignant tumors in vivo. METHODS: On the 5'
      terminus of synthesized single-stranded 17-mer antisense EGFR mRNA antisense PNA
      and mismatched PNA, a 4-amino-acid (Gly-(D)-Ala-Gly-Gly) linker forming an N4
      structure was used for coupling (99m)Tc. Probes were labeled with (99m)Tc by
      ligand exchange. The radiochemical purity of these (99m)Tc-labeled probes was
      determined by reversed-phase high-performance liquid chromatography. Cellular
      uptake, retention, binding specificity, and stability of the probes were studied
      either in vitro or in vivo. Biodistribution and radionuclide imaging were
      performed in BALB/c nude mice bearing SKOV3 (EGFR-positive) or MDA-MB-435S (EGFR
      negative) carcinoma xenografts, respectively. RESULTS: The average labeling
      efficiencies of (99m)Tc-EGFR-PNA and (99m)Tc-CTL-PNA were 98.80% +/- 1.14% and
      98.63% +/- 1.36% (mean +/- SD, n = 6), respectively, within 6 h at room
      temperature, and the radiochemical purity of the probes was higher than 95%.
      (99m)Tc-EGFR-PNA was highly stable in normal saline and fresh human serum at 37
      degrees C in vitro and in urine and plasma samples of nude mice after 2-3 h of
      injection. Cellular uptake and retention ratios of (99m)Tc-EGFR-PNA in SKOV3
      cells were higher than those of (99m)Tc-CTL-PNA and the EGFR-negative control.
      Meanwhile, EGFR mRNA binding (99m)Tc-EGFR-PNA was blocked with an excess of
      unlabeled EGFR-PNA in SKOV3 cell lines. The biodistribution study demonstrated
      accumulation of (99m)Tc-EGFR-PNA primarily in the SKOV3 xenografts and in EGFR
      expressing organs. Radionuclide imaging demonstrated clear localization of
      (99m)Tc-EGFR-PNA in the SKOV3 xenografts shortly after injection but not in
      (99m)Tc-CTL-PNA and the EGFR-negative control. CONCLUSION: (99m)Tc-EGFR-PNA has
      the potential for imaging EGFR mRNA overexpression in tumors.

PMID- 24744448
TI  - Audiovisual integration in the human perception of materials.
AB  - Interest in the perception of the material of objects has been growing. While
      material perception is a critical ability for animals to properly regulate
      behavioral interactions with surrounding objects (e.g., eating), little is known
      about its underlying processing. Vision and audition provide useful information
      for material perception; using only its visual appearance or impact sound, we can
      infer what an object is made from. However, what material is perceived when the
      visual appearance of one material is combined with the impact sound of another,
      and what are the rules that govern cross-modal integration of material
      information? We addressed these questions by asking 16 human participants to rate
      how likely it was that audiovisual stimuli (48 combinations of visual appearances
      of six materials and impact sounds of eight materials) along with visual-only
      stimuli and auditory-only stimuli fell into each of 13 material categories. The
      results indicated strong interactions between audiovisual material perceptions;
      for example, the appearance of glass paired with a pepper sound is perceived as
      transparent plastic. Rating material-category likelihoods follow a multiplicative
      integration rule in that the categories judged to be likely are consistent with
      both visual and auditory stimuli. On the other hand, rating-material properties,
      such as roughness and hardness, follow a weighted average rule. Despite a
      difference in their integration calculations, both rules can be interpreted as
      optimal Bayesian integration of independent audiovisual estimations for the two
      types of material judgment, respectively. 

PMID- 24744449
TI  - Separating monocular and binocular neural mechanisms mediating chromatic
      contextual interactions.
AB  - When seen in isolation, a light that varies in chromaticity over time is
      perceived to oscillate in color. Perception of that same time-varying light may
      be altered by a surrounding light that is also temporally varying in
      chromaticity. The neural mechanisms that mediate these contextual interactions
      are the focus of this article. Observers viewed a central test stimulus that
      varied in chromaticity over time within a larger surround that also varied in
      chromaticity at the same temporal frequency. Center and surround were presented
      either to the same eye (monocular condition) or to opposite eyes (dichoptic
      condition) at the same frequency (3.125, 6.25, or 9.375 Hz). Relative phase
      between center and surround modulation was varied. In both the monocular and
      dichoptic conditions, the perceived modulation depth of the central light
      depended on the relative phase of the surround. A simple model implementing a
      linear combination of center and surround modulation fit the measurements well.
      At the lowest temporal frequency (3.125 Hz), the surround's influence was
      virtually identical for monocular and dichoptic conditions, suggesting that at
      this frequency, the surround's influence is mediated primarily by a binocular
      neural mechanism. At higher frequencies, the surround's influence was greater for
      the monocular condition than for the dichoptic condition, and this difference
      increased with temporal frequency. Our findings show that two separate neural
      mechanisms mediate chromatic contextual interactions: one binocular and dominant
      at lower temporal frequencies and the other monocular and dominant at higher
      frequencies (6-10 Hz). 

PMID- 24744450
TI  - Does mixing of beech (Fagus sylvatica) and spruce (Picea abies) litter hasten
      decomposition?
AB  - BACKGROUND AND AIMS: It is of practical relevance to know how much beech must be
      admixed to pure spruce stands in order to increase litter decomposition and
      associated nutrient cycling, since the formation of thick organic layers is
      commonly ascribed to the recalcitrance of spruce needles. We addressed the impact
      of tree species mixture within forest stands and within litter on mass loss and
      nutritional release from litter. METHODS: Litter decomposition was measured in
      three adjacent stands of pure spruce (Picea abies), mixed beech-spruce and pure
      beech (Fagus sylvatica) on a nutrient-rich site and a nutrient-poor site over a 2
      year period using litterbags which were filled with five different mixtures of
      beech and spruce litter. RESULTS: Mass loss of beech litter was not higher than
      mass loss of spruce litter. Decay was primarily affected by tree species
      composition of the incubation stand and was faster in (mixed) beech forests
      stands than in spruce forests, while the influence of litter species and their
      mixtures on decay rates was small. Net transfers of nutrients between the two
      litter species (direct effects) in the mixed bags were minimal, since initial
      beech and spruce litter did not have different litter quality. However, in a few
      cases indirect effects (e.g., changing decomposer abundance and activity) caused
      non-additive patterns for the totals within the mixed bags, hastening
      decomposition within the first year. CONCLUSIONS: Greater accumulation of litter
      in spruce compared to beech stands is not a consequence of the inherent
      recalcitrance of needles. Adverse environmental conditions in spruce stands
      retard decomposition. Indirect effects on decomposition caused by stand mixture
      are not mimicked by litter mixtures within mesh bags.

PMID- 24744451
TI  - Producing bilinguals through immersion education: Development of metalinguistic
      awareness.
AB  - This study examined metalinguistic awareness in children who were becoming
      bilingual in an immersion education program. The purpose was to determine at what
      point in emerging bilingualism the previously reported metalinguistic advantages
      appear and what types of metalinguistic tasks reveal these developmental
      differences. Participants were 124 children in second and fifth grades who were
      enrolled in either a French immersion or a regular English program. All children
      were from monolingual English-speaking homes and attended local public schools in
      middle socioeconomic neighborhoods. Measures included morphological awareness,
      syntactic awareness, and verbal fluency, with all testing in English. These tasks
      differed in their need for executive control, a cognitive ability that is
      enhanced in bilingual children. Overall, the metalinguistic advantages reported
      in earlier research emerged gradually, with advantages for tasks requiring more
      executive control (grammaticality judgment) appearing later and some tasks
      improving but not exceeding performance of monolinguals (verbal fluency) even by
      fifth grade. These findings demonstrate the gradual emergence of changes in
      metalinguistic concepts associated with bilingualism over a period of about 5
      years. Performance on English-language proficiency tasks was maintained by French
      immersion children throughout in spite of schooling being conducted in French.

PMID- 24744452
TI  - Associations between cortical thickness and general intelligence in children,
      adolescents and young adults.
AB  - Neuroimaging research indicates that human intellectual ability is related to
      brain structure including the thickness of the cerebral cortex. Most studies
      indicate that general intelligence is positively associated with cortical
      thickness in areas of association cortex distributed throughout both brain
      hemispheres. In this study, we performed a cortical thickness mapping analysis on
      data from 182 healthy typically developing males and females ages 9 to 24 years
      to identify correlates of general intelligence (g) scores. To determine if these
      correlates also mediate associations of specific cognitive abilities with
      cortical thickness, we regressed specific cognitive test scores on g scores and
      analyzed the residuals with respect to cortical thickness. The effect of age on
      the association between cortical thickness and intelligence was examined. We
      found a widely distributed pattern of positive associations between cortical
      thickness and g scores, as derived from the first unrotated principal factor of a
      factor analysis of Wechsler Abbreviated Scale of Intelligence (WASI) subtest
      scores. After WASI specific cognitive subtest scores were regressed on g factor
      scores, the residual score variances did not correlate significantly with
      cortical thickness in the full sample with age covaried. When participants were
      grouped at the age median, significant positive associations of cortical
      thickness were obtained in the older group for g-residualized scores on Block
      Design (a measure of visual-motor integrative processing) while significant
      negative associations of cortical thickness were observed in the younger group
      for g-residualized Vocabulary scores. These results regarding correlates of
      general intelligence are concordant with the existing literature, while the
      findings from younger versus older subgroups have implications for future
      research on brain structural correlates of specific cognitive abilities, as well
      as the cognitive domain specificity of behavioral performance correlates of
      normative gray matter thinning during adolescence.

PMID- 24744453
TI  - Sleep reduces false memory in healthy older adults.
AB  - STUDY OBJECTIVES: To investigate the effects of post-learning sleep and sleep
      architecture on false memory in healthy older adults. DESIGN: Balanced, crossover
      design. False memory was induced using the Deese-Roediger-McDermott (DRM)
      paradigm and assessed following nocturnal sleep and following a period of daytime
      wakefulness. Post-learning sleep structure was evaluated using polysomnography
      (PSG). SETTING: Sleep research laboratory. PARTICIPANTS: Fourteen healthy older
      adults from the Singapore-Longitudinal Aging Brain Study (mean age +/- standard
      deviation = 66.6 +/- 4.1 y; 7 males). MEASUREMENTS AND RESULTS: At encoding,
      participants studied lists of words that were semantically related to non
      presented critical lures. At retrieval, they made "remember"/"know" and "new"
      judgments. Compared to wakefulness, post-learning sleep was associated with
      reduced "remember" responses, but not "know" responses to critical lures. In
      contrast, there were no significant differences in the veridical recognition of
      studied words, false recognition of unrelated distractors, discriminability, or
      response bias between the sleep and the wake conditions. More post-learning slow
      wave sleep was associated with greater reduction in false memory. CONCLUSIONS: In
      healthy older adults, sleep facilitates the reduction in false memory without
      affecting veridical memory. This benefit correlates with the amount of slow wave
      sleep in the post-learning sleep episode.

PMID- 24744455
TI  - Motor events during healthy sleep: a quantitative polysomnographic study.
AB  - STUDY OBJECTIVES: Many sleep disorders are characterized by increased motor
      activity during sleep. In contrast, studies on motor activity during
      physiological sleep are largely lacking. We quantitatively investigated a large
      range of motor phenomena during polysomnography in physiological sleep. DESIGN:
      Prospective polysomnographic investigation. SETTING: Academic referral sleep
      laboratory. PARTICIPANTS: One hundred healthy sleepers age 19-77 y were strictly
      selected from a representative population sample by a two-step screening
      procedure. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: Polysomnography
      according to American Academy of Sleep Medicine (AASM) standards was performed,
      and quantitative normative values were established for periodic limb movements in
      sleep (PLMS), high frequency leg movements (HFLM), fragmentary myoclonus (FM),
      neck myoclonus (NM), and rapid eye movement (REM)-related electromyographic (EMG)
      activity. Thirty-six subjects had a PLMS index > 5/h, 18 had a PLMS index > 15/h
      (90th percentile: 24.8/h). Thirty-three subjects had HFLM (90th percentile: four
      sequences/night). All subjects had FM (90th percentile 143.7/h sleep). Nine
      subjects fulfilled AASM criteria for excessive FM. Thirty-five subjects had NM
      (90th percentile: 8.8/h REM sleep). For REM sleep, different EMG activity
      measures for the mentalis and flexor digitorum superficialis muscles were
      calculated: the 90th percentile for phasic mentalis EMG activity for 30-sec
      epochs according to AASM recommendation was 15.6%, and for tonic mentalis EMG
      activity 2.6%. Twenty-five subjects exceeded the recently proposed phasic
      mentalis cutoff of 11%. None of the subjects exceeded the tonic mentalis cutoff
      of 9.6%. CONCLUSION: Quantification of motor phenomena is a basic prerequisite to
      develop normative values, and is a first step toward a more precise description
      of the various motor phenomena present during sleep. Because rates of motor
      events were unexpectedly high even in physiological sleep, the future use of
      normative values for both research and clinical routine is essential.

PMID- 24744454
TI  - Developmental patterns of sleep slow wave activity and synaptic density in
      adolescent mice.
AB  - STUDY OBJECTIVE: In humans sleep slow wave activity (SWA) declines during
      adolescence. It has been suggested that this decline reflects the elimination of
      cortical synapses, but this hypothesis has never been tested directly. DESIGN: We
      focused on mouse frontal cortex and collected data from early adolescence
      (~postnatal day 20, P20) to adulthood (P60) of (1) SWA; (2) expression of
      synapsin I, a presynaptic marker; and (3) number of dendritic spines in layers I
      II. SETTING: Basic sleep research laboratory. PATIENTS OR PARTICIPANTS: YFP-line
      H mice (n = 70; P15-87, all males) and GFP-line S mice (n = 14; P17-60, 8
      females) were used for EEG recording. Forty-five YFP mice (P19-119, 12 females)
      and 42 GFP-S mice (P20-60, 14 females) were used for in vivo 2-photon imaging and
      ex vivo confocal microscopy, respectively. Other YGP mice (n = 57, P10-77) were
      used for western blot analysis of synapsin I. INTERVENTIONS: N/A. MEASUREMENTS
      AND RESULTS: As in humans, SWA in mice declined from early adolescence to
      adulthood. Synapsin I levels increased from P10 to P24, with little change
      afterwards. Mean spine density in apical dendrites of layer V pyramidal neurons
      (YFP-H) showed no change from P20 to P60. Spine number in layers I-II apical
      dendrites, belonging to layer III and V pyramidal neurons (GFP-S), increased
      slightly from P20 to P30 and decreased from P30 to P60; smaller spines decreased
      in number from P20 to P60, while bigger spines increased. CONCLUSIONS: In mice,
      it is unlikely that the developmental decrease in SWA can be accounted for by a
      net pruning of cortical synapses.

PMID- 24744456
TI  - The circadian clock gene Csnk1e regulates rapid eye movement sleep amount, and
      nonrapid eye movement sleep architecture in mice.
AB  - STUDY OBJECTIVES: Efforts to identify the genetic basis of mammalian sleep have
      included quantitative trait locus (QTL) mapping and gene targeting of known core
      circadian clock genes. We combined three different genetic approaches to identify
      and test a positional candidate sleep gene - the circadian gene casein kinase 1
      epsilon (Csnk1e), which is located in a QTL we identified for rapid eye movement
      (REM) sleep on chromosome 15. MEASUREMENTS AND RESULTS: Using
      electroencephalographic (EEG) and electromyographic (EMG) recordings, baseline
      sleep was examined in a 12-h light:12-h dark (LD 12:12) cycle in mice of seven
      genotypes, including Csnk1e(tau/tau) and Csnk1e(-/-) mutant mice, Csnk1e (B6.D2)
      and Csnk1e (D2.B6) congenic mice, and their respective wild-type littermate
      control mice. Additionally, Csnk1e(tau/tau) and wild-type mice were examined in
      constant darkness (DD). Csnk1e(tau/tau) mutant mice and both Csnk1e (B6.D2) and
      Csnk1e (D2.B6) congenic mice showed significantly higher proportion of sleep time
      spent in REM sleep during the dark period than wild-type controls - the original
      phenotype for which the QTL on chromosome 15 was identified. This phenotype
      persisted in Csnk1e(tau/tau) mice while under free-running DD conditions. Other
      sleep phenotypes observed in Csnk1e(tau/tau) mice and congenics included a
      decreased number of bouts of nonrapid eye movement (NREM) sleep and an increased
      average NREM sleep bout duration. CONCLUSIONS: These results demonstrate a role
      for Csnk1e in regulating not only the timing of sleep, but also the REM sleep
      amount and NREM sleep architecture, and support Csnk1e as a causal gene in the
      sleep QTL on chromosome 15.

PMID- 24744458
TI  - Salivary antimicrobial protein response to prolonged running.
AB  - INTRODUCTION: Prolonged exercise may compromise immunity through a reduction of
      salivary antimicrobial proteins (AMPs). Salivary IgA (IgA) has been extensively
      studied, but little is known about the effect of acute, prolonged exercise on
      AMPs including lysozyme (Lys) and lactoferrin (Lac). OBJECTIVE: To determine the
      effect of a 50-km trail race on salivary cortisol (Cort), IgA, Lys, and Lac.
      METHODS: 14 subjects: (6 females, 8 males) completed a 50km ultramarathon. Saliva
      was collected pre, immediately after (post) and 1.5 hrs post race (+1.5).
      RESULTS: Lac concentration was higher at +1.5 hrs post race compared to post
      exercise (p < 0.05). Lys was unaffected by the race (p > 0.05). IgA
      concentration, secretion rate, and IgA/Osm were lower +1.5 hrs post compared to
      pre race (p < 0.05). Cort concentration was higher at post compared to +1.5 (p <
      0.05), but was unaltered from pre race levels. Subjects finished in 7.81+/-1.2
      hrs. Saliva flow rate did not differ between time points. Saliva Osm increased at
      post (p < 0.05) compared to pre race. CONCLUSIONS: The intensity could have been
      too low to alter Lys and Lac secretion rates and thus, may not be as sensitive as
      IgA to changes in response to prolonged running. Results expand our understanding
      of the mucosal immune system and may have implications for predicting illness
      after prolonged running.

PMID- 24744459
TI  - Usefulness and metabolic implications of a 60-second repeated jumps test as a
      predictor of acrobatic jumping performance in gymnasts.
AB  - Gymnastics floor exercises are composed of a set of four to five successive
      acrobatic jumps usually called a "series". The aims of the study were: 1) to
      relate the acrobatic gymnastics performance of these series with a repeated jumps
      test of similar duration (R60), 2) to study the relation between R60 and
      physiological parameters (heart rate and blood lactate), and the performance
      obtained in different kinds of jumps, 3) to confirm whether R60, executed without
      a damped jumping technique, can be considered an anaerobic lactic power test.
      Twenty male and twenty-four female gymnasts performed three repeated jumps tests
      for 5 s (R5), 10 s (R10) and 60 s (R60) and vertical jumps, such as drop jumps
      (DJ), squat jumps (SJ) and countermovement jumps (CMJ). We assessed heart rate
      (HR) and blood lactate during R10 and R60. The average values of the maximal
      blood lactate concentration (Lmax) after R10 (males = 2.5+/-0.6 mmol . l(-1);
      females = 2.1+/-0.8 mmol . l(-1)) confirm that anaerobic glycolysis is not
      activated to a high level. In R60, the Lmax (males = 7.5+/-1.7 mmol . l(-1)
      females = 5.9+/-2.1 mmol . l(-1)) that was recorded does not validate R60 as an
      anaerobic lactic power test. We confirmed the relation between the average power
      obtained in R60 (R60Wm) and the acrobatic performance on the floor. The inclusion
      in the multiple regression equation of the best power in DJ and the best flight
      contact ratio (FC) in R5 confirms the influence of other non-metabolic components
      on the variability in R60 performance, at least in gymnasts. 

PMID- 24744457
TI  - MicroRNAs-role in lung cancer.
AB  - Regulation of gene expression is essential for normal physiological functions;
      thus deregulation of gene expression is common in disease conditions. One level
      of regulation of gene expression is performed by noncoding RNAs, among which
      microRNAs (miRNA) are the best studied. Abnormal expression of these molecular
      players can lead to pathogenic processes such as heart disease, immune system
      abnormalities, and carcinogenesis, to name but a few. Of a length of 18-25
      nucleotides miRNAs are involved in binding partial complementary sequences within
      the 3'-UTR (3'-untranslated region) of the target mRNAs. Depending on the type of
      neoplastic transformation, miRNAs can act both as oncogenes (oncomirs) or as
      tumor suppressors. Because of the great importance of miRNAs, most researches
      focus on either their role as biomarkers or their potential as therapeutic
      targets. Herein, we present the review of microRNA biology, function, and
      tumorigenic potential with emphasis on their role in lung cancer. 

PMID- 24744460
TI  - Intakes of selected nutrients, bone mineralisation and density of adolescent
      female swimmers over a three-year period.
AB  - The aim of this study was to conduct three-year monitoring of bone mineralization
      (BMC) and bone mineral density (BMD) of adolescent girls engaged in swimming at
      the time of attaining the peak bone mass and of their counterparts leading a
      rather sedentary life, considering the intakes of calcium, phosphorus and
      protein, as well as the proportions among those nutrients. Two groups of girls
      aged 11-13 years were studied 3 times at yearly intervals: untrained controls (n
      = 20) and those engaged in competitive swimming (n = 20). Bone density was
      determined by dual-energy X-ray absorptiometry (DXA) in the lumbar spine (L2 -
      L4). Nutrient intakes (energy, protein, calcium, phosphorus) were assessed from
      24-h recalls. The group of swimmers had significantly lower BMI values than the
      control group. No systematic, significant between-group differences were found in
      nutrient intake or in bone mineralization variables. Calcium intake was below the
      recommended norm in all subjects but mean values of bone mineralization variables
      (BMC, BMD) steadily increased in both groups. The BMD z-scores proved negative
      throughout the three-year period of early adolescence in both groups of girls and
      that decrease was significant in swimmers. This could have been due to
      insufficient calcium intake as well as to inadequate calcium-to-phosphate and
      protein-to-calcium ratios and, when continued, might result in a decreased bone
      mass in adulthood. 

PMID- 24744462
TI  - Landing quality in artistic gymnastics is related to landing symmetry.
AB  - In gymnastics every exercise finishes with a landing. The quality of landing
      depends on subjective (e.g. biomechanical) and objective (e.g. mechanical
      characteristics of landing area) factors. The aim of our research was to
      determine which biomechanical (temporal, kinematic and dynamic) characteristics
      of landing best predict the quality of landing. Twelve male gymnasts performed a
      stretched forward and backward salto; also with 1/2, 1/1 and 3/2 turns. Stepwise
      multiple regression extracted five predictors which explained 51.5% of landing
      quality variance. All predictors were defining asymmetries between legs
      (velocities, angles). To avoid asymmetric landings, gymnasts need to develop
      enough height; they need higher angular momentum around the transverse and
      longitudinal axis and they need to better control angular velocity in the
      longitudinal axis. 

PMID- 24744461
TI  - The effect of aerobic training on serum adiponectin and leptin levels and
      inflammatory markers of coronary heart disease in obese men.
AB  - The aim of this study was to investigate the effect of 12 weeks of aerobic
      training on the serum levels of adiponectin and leptin and on inflammatory
      markers of coronary heart disease in obese men. Sixteen non-athlete obese men
      were randomly assigned to one of two experimental groups. The experimental group
      underwent aerobic training consisting of three sessions per week for 12 weeks,
      while the control group did not participate in the training programme during the
      study period. Five millilitres of venous blood was taken from each participant at
      the beginning of the study, during week six and at the end of week 12 to measure
      the levels of leptin, adiponectin, C-reactive protein, interleukin-6 and tumour
      necrosis factor-alpha. The findings showed that aerobic training led to decreases
      in the levels of CRP (P = 0.002), IL-6 (P = 0.001) and leptin (P = 0.003) and an
      increase in the level of adiponectin (P = 0.002) in the experimental group
      relative to the control group. In addition, the level of TNF-alpha decreased in
      the experimental group after the 12-week aerobic training period, although this
      change was not statistically significant. According to the results of this study,
      regular aerobic exercise decreases the potential risk of coronary heart disease
      by improving the plasma levels of IL-6, adiponectin, leptin and CRP.
      Additionally, aerobic exercise can be used as effective non-pharmacological
      treatment to prevent diseases. 

PMID- 24744463
TI  - Effect of music on anaerobic exercise performance.
AB  - For years, mostly the effects of music on cardiorespiratory exercise performance
      have been studied, but a few studies have examined the effect of music on
      anaerobic exercise. The purpose of this study was to assess the effect of
      listening to music and its rhythm on anaerobic exercise: on power output, heart
      rate and the concentration of blood lactate. 28 male subjects were required to
      visit the laboratory on 6 occasions, each separated by 48 hours. Firstly, each
      subject performed the Running-based Anaerobic Sprint Test (RAST) under 3
      conditions on separate days: while listening to "slow rhythm music", "fast rhythm
      music" or "no music". 48 hours after the subjects completed RAST under 3
      conditions, Wingate Anaerobic Power (WAN) tests were performed under 3 music
      conditions. The order of the 3 conditions (slow music, fast music and no music)
      was selected randomly to prevent an order effect. Results showed no significant
      differences between 3 conditions in anaerobic power assessments, heart rate or
      blood lactate (p > 0.05). On the basis of these results it can be said that music
      cannot improve anaerobic performance. The type of music had no impact on power
      outputs during RAST and WAN exercise. As a conclusion, listening to music and its
      rhythm cannot enhance anaerobic performance and cannot change the physiological
      response to supramaximal exercise. 

PMID- 24744464
TI  - Endurance exercise training and diferuloyl methane supplement: changes in
      neurotrophic factor and oxidative stress induced by lead in rat brain.
AB  - Lead is a highly neurotoxic agent that particularly affects the developing
      central nervous system. In the current study we investigated the neuroprotective
      effects of exercise training and/or diferuloyl methane (DM) supplement, which is
      known as curcumin, on lead acetate-induced neurotoxicity in the rat hippocampus.
      Sixty rats were randomly divided into six groups: 1) lead acetate, 2) DM
      supplement, 3) endurance training, 4) training+ DM supplement, 5) sham and 6)
      base. The rats in the training groups performed treadmill running consisting of
      15 to 22 m . min(-1) for 25 to 64 min, 5 times a week for 8 weeks. All groups
      except sham received lead acetate (20 mg . kg(-1)), whereas the sham group
      received DM solvent. In addition, the DM and training + DM groups received DM
      solution (30 mg . kg(-1)) intraperitoneally. Chronic administration of lead
      acetate resulted in a significant increase in the malondialdehyde (MDA) in
      plasma, but not in the hippocampus. In addition, it led to significantly
      decreased brain-derived neurotrophic factor (BDNF) in the hippocampus and total
      antioxidant capacity (TAC) levels, as compared to the sham group. Treadmill
      running, DM supplementation, or both resulted in a significant decrease in MDA
      levels and significantly increased BDNF and TAC levels, as compared to the lead
      acetate group. These results provide a rationale for an inhibitory role of DM
      supplement and regular exercise in the attenuation of lead-induced neurotoxicity.

PMID- 24744465
TI  - External barrel temperature of a small bore olympic rifle and shooting precision.
AB  - Investigations on changes in a rifle's barrel temperature during shooting in a
      rhythm typical for practitioners of Olympic shooting sports are presented.
      Walther KK300 (cal. 5.6 mm), a typical rifle often used in Olympic competitions,
      R50 RWS ammunition and a high speed thermographic camera were used in the study.
      Altair version 5 software was used to process thermal images and a stationary
      wavelet transform was applied to denoise signals for all the studied points. It
      was found that the temperature of the rifle barrel does not exceed 0.3 degrees C
      after one shot whereas the total temperature increase does not exceed 5 degrees C
      after taking 40 shots and does not affect the position of the hitting point on a
      target. In fact, contrary to popular belief, the so-called "warming shots" are
      not done for barrel heating but for cleaning of remnants in the barrel. 

PMID- 24744466
TI  - Development and evaluation of a novel taekwondo chest protector to improve
      mobility when performing axe kicks.
AB  - The axe kick, in Olympic style taekwondo, has been identified as the most popular
      scoring technique aimed to the head during full contact competition. The first
      purpose of this study was to identify and investigate design issues with the
      current World Taekwondo Federation approved chest protector. A secondary purpose
      was to develop a novel chest protector addressing the identified design issues
      and to conduct a biomechanical analysis. Fifteen male elite Taekwondo players
      were selected to perform three different styles of the axe kick, i.e., front, in
      out, and out-in axe kick five times each for a total of 45 kicks. Two-way
      repeated measures ANOVA showed significant differences between the novel and
      existing chest protector conditions for vertical height of the toe, downward
      kicking foot speed, hip flexion angle and ipsilateral shoulder flexion extension
      range of motion (ROM) (p < 0.05). There were no significant differences between
      the control condition (no chest protector) and the novel chest protector
      condition for these variables (p > 0.05). These results indicate that the novel
      chest protector interferes less with both the lower and upper limbs during the
      performance of the axe kick and provides a more natural, free-moving alternative
      to the current equipment used. 

PMID- 24744467
TI  - The +1245g/t polymorphisms in the collagen type I alpha 1 (col1a1) gene in polish
      skiers with anterior cruciate ligament injury.
AB  - OBJECTIVES: The aim of this study was to examine the association of +1245G/T
      polymorphisms in the COL1A1 gene with ACL ruptures in Polish male recreational
      skiers in a case-control study. METHODS: A total of 138 male recreational skiers
      with surgically diagnosed primary ACL ruptures, all of whom qualified for
      ligament reconstruction, were recruited for this study. The control group
      comprised 183 apparently healthy male skiers with a comparable level of exposure
      to ACL injury, none of whom had any self-reported history of ligament or tendon
      injury. DNA samples extracted from the oral epithelial cells were genotyped for
      the +1245G/T polymorphisms using real-time PCR method. RESULTS: Genotype
      distributions among cases and controls conformed to Hardy-Weinberg equilibrium (p
      = 0.2469 and p = 0.33, respectively). There was a significant difference in the
      genotype distribution between skiers and controls (p = 0.045, Fisher's exact
      test). There was no statistical difference in allele distribution: OR 1.43 (0.91
      2.25), p = 0.101 (two-sided Fisher's exact test). CONCLUSIONS: The risk of ACL
      ruptures was around 1.43 times lower in carriers of a minor allele G as compared
      to carriers of the allele T.

PMID- 24744468
TI  - Influence of a low-dose cox-2 inhibitor drug on exercise-induced inflammation,
      muscle damage and lipid peroxidation.
AB  - The purpose of this study was to examine the effect of acute low-dose celecoxib
      administration on exercise-induced inflammation, muscle damage and lipid
      peroxidation. Twenty healthy untrained males (age: 25.5+/-4.5 yrs, weight: 72.7+/
      7.9 kg, height: 177.3+/-7.2 cm) were randomly assigned to treatment (T) or
      placebo (P) groups. Blood samples were obtained before, immediately after, 3 h
      after and 24 h after exercise. Subjects ran for 30 min at 75% [Formula: see
      text]O2 max on a treadmill. Participants consumed 100 mg celecoxib or a placebo
      immediately after and 12 h after the immediately post-exercise blood sample.
      Total leukocytes, neutrophils, creatine kinase (CK), C-reactive protein (CRP) and
      malondialdehyde (MDA) were assessed at each time point. Significant increases in
      total leukocytes and neutrophils were observed 3 h after exercise in both groups
      (P < 0.05). CK and CRP levels were significantly increased immediately, 3 h and
      24 h after exercise in both groups (P < 0.05). A significant increase in MDA was
      observed immediately after exercise in both groups (P < 0.05); however, no
      significant group differences were observed for MDA or CK. These findings suggest
      that inhibition of cyclo-oxygenase activity with low-dose celecoxib does not
      affect exercise-induced inflammation, muscle damage, or lipid peroxidation. 

PMID- 24744469
TI  - Cardiorespiratory fitness, activity level, health-related anthropometric
      variables, sedentary behaviour and socioeconomic status in a sample of Iranian 7
      11 year old boys.
AB  - The purpose of this study was to evaluate cardiorespiratory fitness (CRF),
      activity level, some health-related anthropometric variables, sedentary behaviour
      and socioeconomic status (SES) of 7-11 year old boys in the city of Ardabil,
      Iran. Of 21 253 school boys aged 7-11 years, 766 participated in this study using
      the cluster sampling method. Subjects underwent standard anthropometry. One-mile
      test was used to evaluate [Formula: see text]O2 max. BMI cut-off points were used
      to identify weight status. Child's TV watching and video playing daily time
      (TVVPT) was taken for sedentary behaviour evaluation. SES and activity level were
      measured by standard questionnaires. Of all participants, 8.9% (N=68) of students
      had CRF lower than normal and 58.6% (N=449) of them had inadequate physical
      activity. There was a significant adverse relationship between [Formula: see
      text]O2 max and body mass index (BMI), waist to height ratio (WHtR), waist
      circumference (WC), and fat mass (FM) (p<0.05). A significant direct association
      between SES and both FM and TVVPT was observed (p<0.05). Significantly lower
      physical activity and [Formula: see text]O2 max, and higher TVVPT were observed
      in the obese boys than their counterparts (p<0.05). The results of this study
      indicated a significant relationship between CRF and physical activity, and
      health-related anthropometric variables in a selected sample of 7-11 year boys.
      Moreover, the obese subjects had not only lower physical activity but also longer
      sedentary behaviour time than their counterparts. 

PMID- 24744470
TI  - Effect of exercise on appetite-regulating hormones in overweight women.
AB  - Over the past decade, our knowledge of how homeostatic systems regulate food
      intake and body weight has increased with the discovery of circulating peptides
      such as leptin, acyl ghrelin, des-acyl ghrelin and obestatin. These hormones
      regulate the appetite and food intake by sending signals to the brain regarding
      the body's nutritional status. The purpose of this study was to investigate the
      response of appetite-regulating hormones to exercise. Nine overweight women
      undertook two 2 h trials in a randomized crossover design. In the exercise trial,
      subjects ran for 60 min at 50% of maximal oxygen uptake followed by a 60 min rest
      period. In the control trial, subjects rested for 2 h. Obestatin, acyl ghrelin,
      des-acyl ghrelin and leptin concentrations were measured at baseline and at 20,
      40, 60, 90 and 120 min after baseline. A two-way ANOVA revealed a significant (P
      < 0.05) interaction effect for leptin and acyl ghrelin. However, changes in
      obestatin and des-acyl ghrelin concentration were statistically insignificant (P
      > 0.05). The data indicated that although acute treadmill exercise resulted in a
      significant change in acyl ghrelin and leptin levels, it had no effect on plasma
      obestatin and des-acyl ghrelin levels. 

PMID- 24744471
TI  - Effects of massage under hypoxic conditions on exercise-induced muscle damage and
      physical strain indices in professional soccer players.
AB  - Reports based on experiences from masseurs and players, mostly without any
      scientific background, suggest that the combination of a classical regeneration
      method (i.e. massage) with exposure to hypoxia may enhance regeneration in
      soccer. The aim of this study was to evaluate whether this specific combination
      could affect blood parameters related to muscle damage and physical strain after
      a soccer game. Approximately 15 hours after two separate championship games, 10
      professional male outfield players of the first Austrian division were exposed to
      normobaric hypoxia (FiO2 13.5% ~ 4000m) or normoxia for 1 hour (30 minutes rest
      followed by 30 min massage) (cross-over design). Creatine kinase (CK), urea and
      uric acid (UA) were measured 4 days before the first game, and 15 and 63 hours
      after the two games. Match play increased CK values independently of the
      intervention. No effect of the massage in combination with hypoxia was seen. A
      trend was found between Delta UA ([UA] 48 hours after exposure minus [UA] before
      exposure) in response to hypoxia and SaO2 measured in hypoxia (r=0.612, p=0.06).
      Results show that massage under hypoxic conditions had no additional positive
      effect on the measured parameters compared to massage alone. Solely the trend of
      a relationship for Delta UA and SaO2 might indicate that redox alterations are a
      potential consequence of hypoxic exposure. 

PMID- 24744472
TI  - CATECHOLAMINES AND beta2-ADRENOCEPTOR GENE EXPRESSION BEFORE AND AFTER MAXIMAL
      INCREMENTAL CYCLE TEST IN YOUNG ICE HOCKEY PLAYERS: RELATION TO WORK PERFORMED.
AB  - The aim of this study was to assess the plasma adrenaline and noradrenaline
      concentrations as well as whole blood beta2-adrenoceptor gene (ADRB2) expression
      in young ice hockey players before and immediately after exercise in relation to
      performed work. Nineteen Youth National Team ice hockey players were subjected to
      the maximal incremental cycloergometer exercise. The test was done in the pre
      competitive phase of training. Among many parameters the plasma adrenaline and
      noradrenaline concentrations and ADRB2 gene expression in peripheral blood
      mononuclear cells (PBMC) were determined before and after exercise. The average
      performed work was 3261.3 +/- 558.3 J . kg(-1) and maximal oxygen consumption
      (VO2max) for all players was 53.85 +/- 3.91 mL . kg(-1) min(-1). The geometric
      mean of the ADRB2 gene expression was statistically significantly different
      before and after exercise (P <= 0.05), while adrenaline and noradrenaline levels
      in plasma significantly increased after exercise. In the analysed group of
      athletes we found that initial level of plasma noradrenaline correlated with the
      performed work (r = - 0.55, P < 0.014) and normalized ADRB2 expression before the
      exercise correlated with the work done by them (r = 0.48, P<0.039). However, no
      statistically significant correlations were found between the plasma adrenaline
      or noradrenaline concentrations and ADRB2 gene expression in peripheral blood of
      the players. The performed work in the maximal incremental exercise test of
      regularly training young ice hockey players depends on the initial levels of
      noradrenaline in plasma and ADRB2 mRNA in PBMC. 

PMID- 24744474
TI  - Effects of cyclic static stretch on fatigue recovery of triceps surae in female
      basketball players.
AB  - Static stretch is a safe and feasible method which usually is used before
      exercise to avoid muscle injury and to improve muscle performance. The purpose of
      this study was to determine the effects of cyclic static stretch (CSS) on fatigue
      recovery of triceps surae (TS) in female basketball players. Nine athlete
      volunteers between 20 and 30 years participated in this study containing two
      sessions. After warm-up a pressure cuff was fastened above the knee joint and its
      pressure was increased to 140 mmHg. The subjects were asked to perform one
      maximum voluntary contraction (MVC) followed by a fatigue test including maximum
      isometric fatiguing contraction of TS. These steps were similar in both sessions.
      Then, a two-minute rest was included in the first session while 4 static
      stretches were performed to TS in the second session. After interventions, one
      MVC was done and the pressure cuff was released. During these steps, peak torque
      (PT) and electromyography (EMG) were recorded. The amount of lower leg pain was
      determined by the visual analogue scale (VAS). The value of PT increased
      significantly after CSS but its increase was not significant after rest. It seems
      that the effects of rest and CSS on the EMG parameters, PT and pain are similar. 

PMID- 24744473
TI  - Jump landing characteristics in elite soccer players with cerebral palsy.
AB  - The aim of the present study was to analyse the parameters that characterize the
      vertical ground reaction force during the landing phase of a jump, and to
      determine the relationship among these parameters in elite soccer players with
      cerebral palsy (CP). Thirteen male members of the Spanish national soccer team
      for people with CP (mean age: 27.1 +/- 4.7 years) volunteered for the study. Each
      participant performed three counter movement jumps. The characteristics of the
      first peak of the vertical ground reaction force during the landing phase of a
      jump, which corresponds to the forefoot contact with the ground, were similar to
      the results obtained in previous studies. However, a higher magnitude of rearfoot
      contact with the ground (F2) was observed in participants with CP than in
      participants without CP. Furthermore, a significant correlation between F2
      magnitude and the elapsed time until its production (T2) was not observed (r = 
      0.474 for p = 0.102). This result implies that a landing technique based on a
      delay in the production of F2 might not be effective to reduce its magnitude,
      contrary to what has been observed in participants without CP. The absence of a
      significant correlation between these two parameters in the present study, and
      the high magnitude of F2, suggest that elite soccer players with CP should use
      footwear with proper cushioning characteristics. 

PMID- 24744475
TI  - Assessment of external and internal loads in the triple jump via inverse dynamics
      simulation.
AB  - THE TRIPLE JUMP IS A DEMANDING ATHLETICS EVENT THAT, AFTER AN APPROACH RUN,
      CONSISTS OF THREE CONSECUTIVE PHASES: the hop, the bound, and the jump. During
      the involved three take-off actions a jumper is exposed to increased risk of
      injury due to the high impact forces from the ground and powerful muscle/tendon
      efforts, which are further reflected in the internal loads of the lower limb
      joints. While external ground reactions can possibly be measured using force
      platforms, in vivo measurements of the internal loads are practically not
      feasible. The purpose of the paper is to present the development of an effective
      formulation for the inverse dynamics simulation of the triple jump, based on the
      jumper dynamical model and non-invasive kinematic recordings of the movement. The
      developed simulation model serves for the analysis of all the triple jump phases,
      irrespective of whether the jumper is in flight or in contact with the ground
      with one of his feet, and is focused on effective assessment of the external
      reactions on the supporting leg as well as the muscle forces and joint reaction
      forces in the leg. Some numerical results of inverse dynamics simulation of the
      triple jump are reported. 

PMID- 24744476
TI  - Autonomic control of heart rate after exercise in trained wrestlers.
AB  - The objective of this study was to establish differences in vagal reactivation,
      through heart rate recovery and heart rate variability post exercise, in
      Brazilian jiu-jitsu wrestlers (BJJW). A total of 18 male athletes were evaluated,
      ten highly trained (HT) and eight moderately trained (MT), who performed a
      maximum incremental test. At the end of the exercise, the R-R intervals were
      recorded during the first minute of recovery. We calculated heart rate recovery
      (HRR60s), and performed linear and non-linear (standard deviation of
      instantaneous beat-to-beat R-R interval variability - SD1) analysis of heart rate
      variability (HRV), using the tachogram of the first minute of recovery divided
      into four segments of 15 s each (0-15 s, 15-30 s, 30-45 s, 45-60 s). Between HT
      and MT individuals, there were statistically significant differences in HRR60s (p
      <0.05) and in the non linear analysis of HRV from SD130-45s (p <0.05) and SD145
      60s (p <0.05). The results of this research suggest that heart rate kinetics
      during the first minute after exercise are related to training level and can be
      used as an index for autonomic cardiovascular control in BJJW. 

PMID- 24744477
TI  - Assessment of intake and nutritional status of vitamin b1, b2, and b6 in men and
      women with different physical activity levels.
AB  - The purpose of the present study was to examine the nutritional status of vitamin
      B1, B2, and B6 in respect to dietary intake of these vitamins and activity
      coefficients of the erythrocyte enzymes transketolase, glutathione reductase, and
      aspartic aminotransferase in young men and women with different physical activity
      levels. The participants of this study were 20 women and 20 men with high
      physical activity (groups HAW and HAM, respectively), and 20 women and 20 men
      with low physical activity (groups LAW and LAM, respectively). The intake of
      vitamins B1, B2, B6, proteins, and calorie content of the diet was based on the
      average of the 4-day dietary recalls. To assess nutritional status of vitamin B1,
      B2, and B6, the activity coefficients (alpha) of erythrocyte transketolase (ETK),
      erythrocyte glutathione reductase (EGR), and erythrocyte aspartic
      aminotransferase (EAST) were estimated in blood hemolysates. The intake of the
      studied vitamins in the diet was statistically significantly lower in the female
      groups compared with the respective male groups. Deficiency of vitamin B6 in the
      diet was present more often in women than in men (in terms of the recommended
      dietary allowances [RDA]). Values of the activity coefficient alphaETK indicated
      that none of the groups in this study suffered the risk of vitamin B1 deficiency.
      The value of the activity coefficient alphaEGR indicated that the groups of women
      and men with low physical activity were more prone to vitamin B2 deficiency
      compared with the high physical activity groups. The risk of vitamin B6
      deficiency (alphaEAST) in both male groups was higher than in both female groups.
      The obtained results do not allow for unequivocal determination of the impact of
      sex and the level of physical activity on intake and nutritional status of
      vitamin B1, B2, and B6. Independently of sex and the level of physical activity,
      the women and men consumed insufficient quantities of vitamins B1 and B6,
      although this was not always related to increased values of corresponding
      activity coefficients. 

PMID- 24744478
TI  - Diurnal variation of haemostatic response to exercise in young sedentary males.
AB  - The aim of this study was to evaluate diurnal variations in the haemostatic
      response to submaximal exercise performed by young, sedentary men. Fifteen
      healthy young sedentary males aged 25.6 +/- 1.34 (mean +/- SD) years performed
      two exercise sessions, morning and evening, at 70% of maximal oxygen consumption
      ([Formula: see text]O2max) on a cycle ergometer for 30 min. Platelet count (PC),
      activated partial thromboplastin time (aPTT), prothrombin time (PT), fibrinogen,
      tissue plasminogen activator (tPA) and plasminogen activator inhibitor-1 (PAI-1)
      activity were measured as dependent variables. Exercise produced significant
      increases in PC and fibrinogen for both sessions (P <= 0.05), which returned to
      the resting values after recovery only in the evening session. APTT and PT
      shortened immediately after exercise, which remained after recovery for both
      sessions (P <= 0.01). Exercise presented significant increases in tPA activity (P
      <= 0.001), which returned to the baseline after recovery in both exercises. PAI-1
      activity was significantly higher during the morning than evening (P <= 0.05),
      but no longer demonstrated exercise-related changes. It was found that exercise
      caused activation of both coagulation and fibrinolysis processes, partly related
      to the time of the day when the exercise was performed. 

PMID- 24744479
TI  - Maximum number of repetitions, total weight lifted and neuromuscular fatigue in
      individuals with different training backgrounds.
AB  - The aim of this study was to evaluate the performance, as well as neuromuscular
      activity, in a strength task in subjects with different training backgrounds.
      Participants (n = 26) were divided into three groups according to their training
      backgrounds (aerobic, strength or mixed) and submitted to three sessions: (1)
      determination of the maximum oxygen uptake during the incremental treadmill test
      to exhaustion and familiarization of the evaluation of maximum strength (1RM) for
      the half squat; (2) 1RM determination; and (3) strength exercise, four sets at
      80% of the 1RM, in which the maximum number of repetitions (MNR), the total
      weight lifted (TWL), the root mean square (RMS) and median frequency (MF) of the
      electromyographic (EMG) activity for the second and last repetition were
      computed. There was an effect of group for MNR, with the aerobic group performing
      a higher MNR compared to the strength group (P = 0.045), and an effect on MF with
      a higher value in the second repetition than in the last repetition (P = 0.016).
      These results demonstrated that individuals with better aerobic fitness were more
      fatigue resistant than strength trained individuals. The absence of differences
      in EMG signals indicates that individuals with different training backgrounds
      have a similar pattern of motor unit recruitment during a resistance exercise
      performed until failure, and that the greater capacity to perform the MNR
      probably can be explained by peripheral adaptations. 

PMID- 24744481
TI  - 3d human motion retrieval based on human hierarchical index structure.
AB  - With the development and wide application of motion capture technology, the
      captured motion data sets are becoming larger and larger. For this reason, an
      efficient retrieval method for the motion database is very important. The
      retrieval method needs an appropriate indexing scheme and an effective similarity
      measure that can organize the existing motion data well. In this paper, we
      represent a human motion hierarchical index structure and adopt a nonlinear
      method to segment motion sequences. Based on this, we extract motion patterns and
      then we employ a fast similarity measure algorithm for motion pattern similarity
      computation to efficiently retrieve motion sequences. The experiment results show
      that the approach proposed in our paper is effective and efficient. 

PMID- 24744480
TI  - Changes in the anaerobic threshold in an annual cycle of sport training of young
      soccer players.
AB  - The aim of the study was to assess changes in the anaerobic threshold of young
      soccer players in an annual training cycle. A group of highly trained 15-18 year
      old players of KKS Lech Poznan were tested. The tests included an annual training
      macrocycle, and its individual stages resulted from the time structure of the
      sports training. In order to assess the level of exercise capacities of the
      players, a field exercise test of increasing intensity was carried out on a
      soccer pitch. The test made it possible to determine the 4 millimolar lactate
      threshold (T LA 4 mmol . l(-1)) on the basis of the lactate concentration in
      blood [LA], to establish the threshold running speed and the threshold heart rate
      [HR]. The threshold running speed at the level of the 4 millimolar lactate
      threshold was established using the two-point form of the equation of a straight
      line. The obtained indicators of the threshold running speed allowed for precise
      establishment of effort intensity used in individual training in developing
      aerobic endurance. In order to test the significance of differences in mean
      values between four dates of tests, a non-parametric Friedman ANOVA test was
      used. The significance of differences between consecutive dates of tests was
      determined using a post-hoc Friedman ANOVA test. The tests showed significant
      differences in values of selected indicators determined at the anaerobic
      threshold in various stages of an annual training cycle of young soccer players.
      The most beneficial changes in terms of the threshold running speed were noted on
      the fourth date of tests, when the participants had the highest values of 4.01 m
      . s(-1) for older juniors, and 3.80 m . s(-1) for younger juniors. This may be
      indicative of effective application of an individualized programme of training
      loads and of good preparation of teams for competition in terms of players'
      aerobic endurance. 

PMID- 24744482
TI  - Genes in sport and doping.
AB  - Genes control biological processes such as muscle production of energy,
      mitochondria biogenesis, bone formation, erythropoiesis, angiogenesis,
      vasodilation, neurogenesis, etc. DNA profiling for athletes reveals genetic
      variations that may be associated with endurance ability, muscle performance and
      power exercise, tendon susceptibility to injuries and psychological aptitude.
      Already, over 200 genes relating to physical performance have been identified by
      several research groups. Athletes' genotyping is developing as a tool for the
      formulation of personalized training and nutritional programmes to optimize sport
      training as well as for the prediction of exercise-related injuries. On the other
      hand, development of molecular technology and gene therapy creates a risk of non
      therapeutic use of cells, genes and genetic elements to improve athletic
      performance. Therefore, the World Anti-Doping Agency decided to include
      prohibition of gene doping within their World Anti-Doping Code in 2003. In this
      review article, we will provide a current overview of genes for use in athletes'
      genotyping and gene doping possibilities, including their development and
      detection techniques. 

PMID- 24744483
TI  - The association of gene polymorphisms with athlete status in ukrainians.
AB  - Athletic performance is a polygenic trait influenced by both environmental and
      genetic factors. OBJECTIVE: To investigate individually and in combination the
      association of common gene polymorphisms with athlete status in Ukrainians.
      METHODS: A total of 210 elite Ukrainian athletes (100 endurance-oriented and 110
      power-orientated athletes) and 326 controls were genotyped for ACE I/D, HIF1A
      Pro582Ser, NOS3 -786 T/C, PPARA intron 7 G/C, PPARG Pro12Ala and PPARGC1B
      Ala203Pro gene polymorphisms, most of which were previously reported to be
      associated with athlete status or related intermediate phenotypes in different
      populations. RESULTS: Power-oriented athletes exhibited an increased frequency of
      the HIF1A Ser (16.1 vs. 9.4%, P = 0.034) and NOS3 T alleles (78.3 vs. 66.2%, P =
      0.0019) in comparison with controls. Additionally, we found that the frequency of
      the PPARG Ala allele was significantly higher in power-oriented athletes compared
      with the endurance-oriented athletes (24.7 vs. 13.5%; P = 0.0076). Next, we
      determined the total genotype score (TGS, from the accumulated combination of the
      three polymorphisms, with a maximum value of 100 for the theoretically optimal
      polygenic score) in athletes and controls. The mean TGS was significantly higher
      in power-oriented athletes (39.1 +/- 2.3 vs. 32.6 +/- 1.5; P = 0.0142) than in
      controls. CONCLUSIONS: We found that the HIF1A Ser, NOS3 T and PPARG Ala alleles
      were associated with power athlete status in Ukrainians.

PMID- 24744484
TI  - Change in blood gelsolin concentration in response to physical exercise.
AB  - Plasma gelsolin (pGSN) produced by muscle is an abundant protein of extracellular
      fluids capable of severing actin filaments and eliminating actin from the
      circulation. Additionally, pGSN modulates the cellular effects of some bioactive
      lipids. In this study we test the hypothesis that hormonal and metabolic
      adaptations to exercise are associated with changes in gelsolin concentration in
      blood. Plasma samples were collected from twenty healthy males recruited from
      untrained (UT, n=10) and endurance trained (ET, n=10) groups that performed 30-60
      minutes of exercise on a cycloergometer at a workload corresponding to 70% of
      VO2max. Gelsolin concentration was determined by quantitative Western blot
      analysis with an anti-human gelsolin antibody. The gelsolin concentration in UT
      and ET subjects before starting exercise ranged from 104 to 330 and 163 to 337 ug
      . ml(-1) respectively. After 30 minutes of exercise we observed a significant
      decrease of plasma gelsolin in the UT group (p<0.05) while the gelsolin
      concentration in the ET group rose on average from 244 to 271 ug . ml(-1).
      However, this increase did not reach statistical significance. Endurance training
      might increase the ability of muscle tissue to express plasma gelsolin as part of
      an adaptive mechanism. 

PMID- 24744485
TI  - Monitoring training loads, stress, immune-endocrine responses and performance in
      tennis players.
AB  - The study aim was to investigate the effect of a periodised pre-season training
      plan on internal training load and subsequent stress tolerance, immune-endocrine
      responses and physical performance in tennis players. Well-trained young tennis
      players (n = 10) were monitored across the pre-season period, which was divided
      into 4 weeks of progressive overloading training and a 1-week tapering period.
      Weekly measures of internal training load, training monotony and stress tolerance
      (sources and symptoms of stress) were taken, along with salivary testosterone,
      cortisol and immunoglobulin A. One repetition maximum strength, running
      endurance, jump height and agility were assessed before and after training. The
      periodised training plan led to significant weekly changes in training loads
      (i.e. increasing in weeks 3 and 4, decreasing in week 5) and post-training
      improvements in strength, endurance and agility (P < 0.05). Cortisol
      concentration and the symptoms of stress also increased in weeks 3 and/or 4,
      before returning to baseline in week 5 (P < 0.05). Conversely, the testosterone
      to cortisol ratio decreased in weeks 3 and 4, before returning to baseline in
      week 5 (P < 0.05). In conclusion, the training plan evoked adaptive changes in
      stress tolerance and hormonal responses, which may have mediated the improvements
      in physical performance. 

PMID- 24744486
TI  - Differences in ground contact time explain the less efficient running economy in
      north african runners.
AB  - The purpose of this study was to investigate the relationship between
      biomechanical variables and running economy in North African and European
      runners. Eight North African and 13 European male runners of the same athletic
      level ran 4-minute stages on a treadmill at varying set velocities. During the
      test, biomechanical variables such as ground contact time, swing time, stride
      length, stride frequency, stride angle and the different sub-phases of ground
      contact were recorded using an optical measurement system. Additionally, oxygen
      uptake was measured to calculate running economy. The European runners were more
      economical than the North African runners at 19.5 km . h(-1), presented lower
      ground contact time at 18 km . h(-1) and 19.5 km . h(-1) and experienced later
      propulsion sub-phase at 10.5 km . h(-1),12 km . h(-1), 15 km . h(-1), 16.5 km .
      h(-1) and 19.5 km . h(-1) than the European runners (P < 0.05). Running economy
      at 19.5 km . h(-1) was negatively correlated with swing time (r = -0.53) and
      stride angle (r = -0.52), whereas it was positively correlated with ground
      contact time (r = 0.53). Within the constraints of extrapolating these findings,
      the less efficient running economy in North African runners may imply that their
      outstanding performance at international athletic events appears not to be linked
      to running efficiency. Further, the differences in metabolic demand seem to be
      associated with differing biomechanical characteristics during ground contact,
      including longer contact times. 

PMID- 24744487
TI  - Anaerobic capacity of amateur mountain bikers during the first half of the
      competition season.
AB  - Sustained aerobic exercise not only affects the rate of force development but
      also decreases peak power development. The aim of this study was to investigate
      whether anaerobic power of amateur mountain bikers changes during the first half
      of the competition season. Eight trained cyclists (mean +/- SE: age: 22.0 +/-0.5
      years; height: 174.6 +/- 0.9 cm; weight: 70.7 +/- 2.6 kg) were subjected to an
      ergocycle incremental exercise test and to the Wingate test on two occasions:
      before, and in the middle of the season. After the incremental exercise test the
      excess post-exercise oxygen consumption was measured during 5-min recovery. Blood
      lactate concentration was measured in the 4th min after the Wingate test. Maximum
      oxygen uptake increased from 60.0 +/- 1.5 ml min(-1) kg(-1) at the beginning of
      the season to 65.2 +/- 1.4 ml min(-1) kg(-1) (P < 0.05) in the season. Neither of
      the mechanical variables of the Wingate test nor excess post-exercise oxygen
      consumption values were significantly different in these two measurements.
      However, blood lactate concentration was significantly higher (P < 0.001) in
      season (11.0 +/- 0.5 mM) than before the season (8.6 +/- 0.4 mM). It is concluded
      that: 1) despite the increase of cyclists' maximum oxygen uptake during the
      competition season their anaerobic power did not change; 2) blood lactate
      concentration measured at the 4th min after the Wingate test does not properly
      reflect training-induced changes in energy metabolism. 

PMID- 24744488
TI  - The competitive demands of elite male rink hockey.
AB  - The aim of this study was to simulate the activity pattern of rink hockey by
      designing a specific skate test (ST) to study the energy expenditure and
      metabolic responses to this intermittent high-intensity exercise and extrapolate
      the results from the test to competition. Six rink hockey players performed, in
      three phases, the 20-metre multi-stage shuttle roller skate test, a tournament
      match and the ST. Heart rate was monitored in all three phases. Blood lactate,
      oxygen consumption, ventilation and respiratory exchange ratio were also recorded
      during the ST. Peak HR was 190.7+/-7.2 beats . min(-1). There were no differences
      in peak HR between the three tests. Mean HR was similar between the ST and the
      match (86% and 87% of HRmax, respectively). Peak and mean ventilation averaged
      111.0+/-8.8 L . min(-1) and 70.3+/-14.0 L (.) min(-1) (60% of VEmax),
      respectively. VO2max was 56.3+/-8.4 mL . kg(-1) . min(-1), and mean oxygen
      consumption was 40.9+/-7.9 mL . kg(-1) (.) min(-1) (70% of VO2max). Maximum blood
      lactate concentration was 7.2+/-1.3 mmol . L-1. ST yielded an energy expenditure
      of 899.1+/-232.9 kJ, and energy power was 59.9+/-15.5 kJ . min(-1). These
      findings suggest that the ST is suitable for estimating the physiological demands
      of competitive rink hockey, which places a heavy demand on the aerobic and
      anaerobic systems, and requires high energy consumption. 

PMID- 24744489
TI  - The effects of back extension training on back muscle strength and spinal range
      of motion in young females.
AB  - The objective of this study was to determine the effects of a 10-week dynamic
      back extension training programme and its effects on back muscle strength, back
      muscle endurance and spinal range of motion (ROM) for healthy young females.
      Seventy-three young females (age: 19.32+/-1.80 years, height: 158.89+/-4.71 cm,
      body weight: 55.67+/-6.30 kg) volunteered for the study. Prior to the training
      period, all participants completed anthropometric measurements, back muscle
      strength and endurance test, lateral bending and spinal ROM measurements. After
      measurements, the participants were divided into two groups. The exercise group
      (N:35) performed the dynamic back extension exercise 3 days per week for 10
      weeks. The control group (N:38) did not participate in any type of exercise. The
      mixed design ANOVA (group x time) was used to determine the difference in pre-
      and post-training values. The present findings show that there were significant
      differences between pre-training and post-training values for back muscle
      strength and spinal ROM in the exercise group. Following the dynamic strength
      training programme, back muscle strength and spine ROM values except flexion of
      the lumbar 5-sacrum 1 (L5-S1) segment of the exercise group showed a significant
      increase when compared with the pre test values. The control group did not show
      any significant changes when compared with the pre-training values. The results
      demonstrate that the 10-week dynamic strength training programme was effective
      for spinal extension ROM and back muscle strength, but there was no change in
      back muscle endurance. In this context, this programme could potentially be used
      to prevent the decrease of spinal ROM as well as provide an increase in the
      fitness parameters of healthy individuals. 

PMID- 24744490
TI  - The effect of aerobic continuous and interval training on left ventricular
      structure and function in male non-athletes.
AB  - Exercise plays an important role to improve cardiovascular performance. The aim
      of this study was to compare the effect of aerobic continuous and interval
      training on the left ventricular structure and function. Twenty untrained healthy
      male students (aged 18-22 years) were randomly divided into two groups:
      continuous (C; n = 10) and interval (I; n = 10). The training programme consisted
      of countryside jogging for 45 min during 8 weeks three times a week at 70% of
      maximum heart rate (MHR). In each session group C was jogging for 45 min and in
      group I jogging was performed in 5 nine-minute stages with a four-minute inactive
      rest between them. M-mode, 2-dimensional, colour and Doppler transthoracic
      echocardiography were performed, during resting conditions, before and after the
      training period. After 8-week training the end diastolic diameter, systolic blood
      pressure and diastolic blood pressure in groups C and I, and the posterior wall
      thickness and the end systolic diameter in group I showed no significant
      difference (P > 0.05). On the other hand, the percentage of ejection fraction and
      shortening fraction in groups C and I, the end systolic diameter and the
      posterior wall thickness in group C and the interventricular septum thickness in
      group I demonstrated a significant difference (P <= 0.05). Comparing the two
      groups, only the value of the interventricular septum thickness was significant
      (P <= 0.05). In general, eight-week aerobic continuous and interval training can
      affect left ventricular structure and function. 

PMID- 24744491
TI  - Kinematic variables and blood Acid-base status in the analysis of collegiate
      swimmers' anaerobic capacity.
AB  - Short duration repeated maximal efforts are often used in swimming training to
      improve lactate tolerance, which gives swimmers the ability to maintain a high
      work rate for a longer period of time. The aim of the study was to examine the
      kinematics of swimming and its relation to the changes in blood acid-base status
      and potassium level. Seven collegiate swimmers, with at least 6 years of training
      experience, volunteered to participate in the study. The test consisted of 8 x 25
      m front crawl performed with maximum effort. The rest period between repetitions
      was set to five seconds. Blood samples were taken from the fingertip at rest,
      after warm-up and in the 3rd minute after completion of the test. The swimming
      was recorded with a video recorder, for later analysis of time, velocity and
      technique (stroke index). Based on the swimming velocity results, the obtained
      curve can be divided into rapid decrease of velocity and relatively stable
      velocities. The breaking point of repetition in swimming velocity was assumed as
      the swimming velocity threshold and it was highly correlated with the decrease of
      the blood acid-base status (pH r=0.82, BE r=0.87, HCO3 (-) r=0.76; p<0.05 in all
      cases). There was no correlation between stroke index or fatigue index and blood
      acid-base status. Analysis of the swimming speed in the 8 x 25 m test seems to be
      helpful in evaluation of lactate tolerance (anaerobic capacity) in collegiate
      swimmers. 

PMID- 24744492
TI  - The relevant use of the traditional tunisian game ''raqassa'' for cardiovascular
      stimulation in schoolchildren.
AB  - The aim of this study was to investigate the heart rate (HR) responses, the rate
      of perceived exertion (RPE), and the feeling during physical education schooling
      while performing traditional games activities compared to intermittent exercise.
      Nineteen pre-pubertal children randomly performed on different days two types of
      lessons (intermittent running mode vs. traditional Tunisian "Raqassa" game)
      lasting 12-min each. HR was continuously recorded during both lessons, while
      ratings of perceived exertion and Feeling values were recorded after the
      sessions. The mean HR value during the traditional game was significantly higher
      than during intermittent exercise (p<0.05). Conversely, the perceived exertion
      score was significantly higher after intermittent exercise than the traditional
      exercise game (p<0.05), showing that the higher cardiovascular strain of the game
      was perceived as "lighter" than the run. Simultaneously, the children's Feeling
      was significantly higher after the traditional game than intermittent exercise
      (p<0.001), showing a higher satisfaction from playing with respect to running.
      Exercise based on the "Raqassa" traditional game could be used in pre-pubertal
      children as an alternative or as an additional method for suitable cardiovascular
      stimulation during physical education lessons with lower perceived exertion and
      better feeling compared to intermittent running. 

PMID- 24744493
TI  - Specific sites of bone expansion depend on the level of volleyball practice in
      prepubescent boys.
AB  - The purpose of this study was to investigate the effect of 18 months of high and
      low levels of volleyball practice on bone acquisition. 130 prepubescent boys
      (mean age 11.4 +/- 0.7) were divided into a high-level training group (HLG), low
      level training group (LLG), and controls. Bone mineral content (BMC) and bone
      area at the whole body, lumbar spine L2-L4, femoral neck of the dominant leg, and
      right and left radius were measured using dual-photon X-ray absorptiometry.
      Enhanced BMC resulted from high-training volleyball activity in all measured
      sites except the third left and right distal radius, which is not modified by low
      level training in prepubescent players but it was accompanied by a bone area
      expansion in radius and weight-bearing sites for the HLG, and in legs, whole
      right and left radius for the LLG. Significant improvement of skeletal tissues is
      associated with the intensity and duration of volleyball training. 

PMID- 24744494
TI  - A 24-hour ambulatory ecg monitoring in assessment of qt interval duration and
      dispersion in rowers with physiological myocardial hypertrophy.
AB  - Myocardial hypertrophy (MH) due to cardiac pathology is characterized by an
      increase in QT interval duration and dispersion, while the findings for exercise
      induced myocardial hypertrophy are contradictory. The majority of published
      research findings have not explored this relationship, but there have only been a
      few conducted studies using 24-hour ECG monitoring. The aim of the study was to
      determine the QT interval duration and dispersion in short-term and 24-hour ECG
      in endurance athletes with myocardial hypertrophy and without it. METHODS: A
      total of 26 well-trained rowers underwent a resting 12-lead ECG, 24-hour ECG
      monitoring and echocardiography. RESULTS: Athletes with MH (n = 7) at rest did
      not show any increase in QTc interval duration and dispersion, or mean and
      maximal QTc duration in Holter monitoring compared to athletes without MH (n =
      19). Left ventricular mass was not significantly correlated with any QTc
      characteristics. Furthermore, athletes with MH had significantly longer mean QT
      (P = 0.01) and maximal QT (P = 0.018) intervals in Holter monitoring and higher
      24-hour heart rate variability indexes due to stronger vagal effects.
      CONCLUSIONS: The present study demonstrated that athlete's heart syndrome with
      myocardial hypertrophy as a benign phenomenon does not lead to an increase in QT
      interval duration, or increases in maximal and mean duration in a 24-hour ECG. An
      increase in QT interval duration in athletes may have an autonomic nature.

PMID- 24744495
TI  - Salivary IL-21 and IgA responses to a competitive match in elite basketball
      players.
AB  - Athletes engaged in strenuous training might experience transient immune
      suppression that could lead to greater incidence of upper respiratory tract
      infections (URTI). Since interleukin 21 (IL-21) stimulates immunoglobulin A (IgA)
      secreting cells and a low level of this immunoglobulin is associated with
      increased incidence of URTI, the aim of the present study was to investigate the
      effect of a basketball match on salivary cortisol (sC), salivary IL-21 (sIL-21)
      and salivary IgA (sIgA) levels. Twenty male basketball players participated in an
      official game in two teams (10 players in each team). The saliva samples were
      collected before the warm-up and approximately 10-15 min after the end of the
      match and were analysed by ELISA methods. sC concentration increased
      significantly after the match while sIL-21 level was reduced (p < 0.05). In
      opposition to the study's hypothesis, sIgA level did not change in response to
      the match. The present findings suggest that a basketball match is sufficiently
      stressful to elevate sC concentration and attenuates the sIL-21 output without
      compromising the sIgA level. It is reasonable to speculate that the stability of
      sIgA acute responses to the match, despite the decrement in sIL-21, indicates
      that other mechanisms rather than IL-21 stimulating B cell
      proliferation/differentiation might modulate IgA concentration and secretion
      rate. 

PMID- 24744496
TI  - Kinematics that differentiate the beach flags start between elite and non-elite
      sprinters.
AB  - This study differentiated the kinematics of the beach flags sprint start between
      five elite (three males, two females; age = 21.2 +/- 2.6 years; height = 1.71 +/-
      0.04 m; mass = 66.2 +/- 5.9 kg) and five non-elite (three males, two females; age
      = 20.4 +/- 1.7 years; height = 1.69 +/- 0.08 meters [m]; mass = 61.6 +/- 5.7
      kilograms) sprinters. A high-speed camera filmed the start. Timing gates recorded
      the 0-2, 0-5, and 0-20 m intervals. Data included body position during the start
      and at take-off; start time; first step length; and sprint times. A Mann-Whitney
      U-test determined significant (p < 0.05) between-group differences; effect sizes
      (ES) were also calculated. Elite sprinters had a greater take-off trajectory
      angle (p = 0.01; ES = 2.57), and were faster over the 0-2 (p = 0.02; ES = 1.77),
      0-5 (p = 0.05; ES = 1.20), and 0-20 m (p = 0.02; ES = 1.83) intervals. Large
      effects were found for: greater take-off swing leg hip flexion (ES = 1.13) and
      trunk lean (ES = 1.37); longer duration start time (ES = 1.33); and longer first
      step length (ES = 1.23) in elite sprinters. A longer start time assists with
      force generation, which in conjunction with increased hip flexion, could
      translate to a longer first step. Increased trunk lean shifts the take-off
      trajectory angle towards the horizontal. A greater trajectory angle at start take
      off, which could be advantageous for force production during sprint performance,
      is likely necessary for beach flags. 

PMID- 24744497
TI  - Biomechanics of head injury in olympic taekwondo and boxing.
AB  - OBJECTIVE: The purpose was to examine differences between taekwondo kicks and
      boxing punches in resultant linear head acceleration (RLA), head injury criterion
      (HIC15), peak head velocity, and peak foot and fist velocities. Data from two
      existing publications on boxing punches and taekwondo kicks were compared.
      METHODS: For taekwondo head impacts a Hybrid II Crash Dummy (Hybrid II) head was
      instrumented with a tri-axial accelerometer mounted inside the Hybrid II head.
      The Hybrid II was fixed to a height-adjustable frame and fitted with a protective
      taekwondo helmet. For boxing testing, a Hybrid III Crash Dummy head was
      instrumented with an array of tri-axial accelerometers mounted at the head centre
      of gravity. RESULTS: Differences in RLA between the roundhouse kick (130.11+/
      51.67 g) and hook punch (71.23+/-32.19 g, d = 1.39) and in HIC15 (clench axe
      kick: 162.63+/-104.10; uppercut: 24.10+/-12.54, d = 2.29) were observed.
      CONCLUSIONS: Taekwondo kicks demonstrated significantly larger magnitudes than
      boxing punches for both RLA and HIC.

PMID- 24744499
TI  - Mechanical analysis of the roundhouse kick according to height and distance in
      taekwondo.
AB  - Competition regulation in taekwondo has experienced several changes during the
      last few years, for example, kicks to the head score more points than kicks to
      the chest. In addition, some external factors such as the height of target and
      execution distance seem to affect the kick performance. The aim of this study was
      to analyse selected biomechanical parameters (impact force, reaction time, and
      execution time) according to the height and execution distance in two different
      male groups (experts (n = 12) and novices (n = 21)). Athletes kicked twice from
      every execution distance (short, normal and long) and towards two different
      heights of target (chest and head) in a random order. Novices kicked to the head
      with a longer reaction time than to the chest (p < 0.05) but experts were able to
      kick with similar performance for both heights. From short and normal distances
      experts kicked with similar performance; whereas from the normal distance novices
      had longer reaction and execution time than from the short distance (p < 0.05).
      In conclusion, in counterattacking situations, experts should perform the
      roundhouse kick to the head instead of to the chest, because it produces better
      scores with similar performance; whereas novice athletes should avoid kicking to
      the head because they are not able to kick with similar performance. Moreover, it
      is recommended that during counterattacks higher-level taekwondo athletes should
      intend to kick from normal distances. 

PMID- 24744498
TI  - Comparison of anthropometric characteristics between professional triathletes and
      cyclists.
AB  - Anthropometric characteristics of athletes are considered to be an important
      determinant of success in sport. The aim of the present study was to compare
      several anthropometric parameters and subjective characteristics of professional
      elite triathletes with anthropometric profiles of professional cyclists and
      sportive students. In total 93 volunteers (21 male and female triathletes, 26
      male cyclists and as a control group 46 male and female students) participated in
      this study. Eight different anthropometric parameters were measured and a five
      page questionnaire containing 35 general questions had to be completed.
      Interestingly, there were no significant differences between the arm span, the
      lengths of the lower limb and the circumference of waist and hip between male
      triathletes and cyclists. As expected, the athletes had significantly lower heart
      rates and lower weights as compared to the controls. Further results showed that
      male cyclists had a higher BMI, larger thighs and were taller as compared to the
      male triathletes. The present study could not evaluate specific anthropometric
      characteristics as predictive factors of performance in elite athletes. Thus,
      individual successful performance is linked to discipline and talent rather than
      to a specific anthropometric profile. 

PMID- 24744500
TI  - Training load, immune system, upper respiratory symptoms and performance in well
      trained cyclists throughout a competitive season.
AB  - This study aimed to evaluate the leukocyte subset counts, serum immunoglobulin A,
      performance and upper respiratory symptoms (URS), as well as their
      interrelationships, of well-trained cyclists for a 29-week training season using
      monitored loads. The season was divided into three phases: preparatory (nine
      weeks), first competitive phase (nine weeks) and second competitive phase (11
      weeks). The sample consisted of eight well-trained cyclists, aged 18 +/- 2 years.
      Immunological parameters and performance were evaluated during weeks 1
      (baseline), 10 (early first competitive phase), 19 (early second competitive
      phase) and 29 (end of the second competitive phase). The training loads (volume x
      rating of perceived exertion) were monitored daily while the monitoring of URS
      was performed every 15 days using the WURSS-44 questionnaire. The data were
      analyzed using a one-way ANOVA and a Pearson correlation test with the
      significance level set at p <= 0.05. No significant differences were found for
      training load, leukocyte subset counts or serum immunoglobulin A among the three
      phases. However, serum immunoglobulin A was 50.9% below the control group values.
      URS were significantly higher during the preparatory period, and there were
      significant correlations between URS and training load (strain) in the
      preparatory period (r = 0.72, p = 0.032) and second competitive phase (r = 0.73,
      p = 0.036). In conclusion, indicators of training load without a significant
      change throughout the season did not significantly affect immune parameters
      measured; however, the increase of strain can cause an increase of upper
      respiratory symptoms throughout the season, but without loss of performance. 

PMID- 24744501
TI  - Beneficial effects of judo training on bone mineral density of high-school boys
      in Korea.
AB  - Bone mineralization is strongly stimulated by weight-bearing exercise during
      growth and development. Judo, an Olympic combat sport, is a well-known form of
      strenuous and weight-bearing physical activity. Therefore, the primary goal of
      this study was to determine the effects of Judo practice on the bone health of
      male high school students in Korea. The secondary goal of this study was to
      measure and compare the bone mineral density (BMD) of the hands of Judo players
      and sedentary control subjects. Thirty Judo players (JDP) and 30 sedentary high
      school boys (CON) voluntarily participated in the present study, and all of the
      sedentary control subjects were individually matched to the Judo players by body
      weight. BMD was determined by using dual-energy X-ray absorptiometry (Hologic,
      Bedford, MA, USA). The lumbar spine, femur and forearm BMD in the JDP group were
      significantly greater by 22.7%, 24.5%, and 18.3%, respectively, than those in the
      CON group. In addition, a significant difference in the CON group was observed
      between the dominant hand (DH) radius (0.710 +/- 0.074 g/cm(2)) and the non
      dominant hand (NDH) radius (0.683 +/- 0.072 g/cm(2)), but this was not observed
      in the JDP group (DH = 0.819 +/- 0.055 g/cm(2); NDH = 810 +/- 0.066 g/cm(2)) (P <
      0.05). Therefore, the results of this study suggest that Judo practice during the
      growth period significantly improves bone health in high school male students. In
      addition, it seems that Judo practice could eliminate the effect of increased BMD
      in the dominant hand. 

PMID- 24744502
TI  - High-intensity exercise training induces morphological and biochemical changes in
      skeletal muscles.
AB  - IN THE PRESENT STUDY WE INVESTIGATED THE EFFECT OF TWO DIFFERENT EXERCISE
      PROTOCOLS ON FIBRE COMPOSITION AND METABOLISM OF TWO SPECIFIC MUSCLES OF MICE:
      the quadriceps and the gastrocnemius. Mice were run daily on a motorized
      treadmill, at a velocity corresponding to 60% or 90% of the maximal running
      velocity. Blood lactate and body weight were measured during exercise training.
      We found that at the end of training the body weight significantly increased in
      high-intensity exercise mice compared to the control group (P=0.0268), whereas it
      decreased in low-intensity exercise mice compared to controls (P=0.30). In
      contrast, the food intake was greater in both trained mice compared to controls
      (P < 0.0001 and P < 0.0001 for low-intensity and high-intensity exercise mice,
      respectively). These effects were accompanied by a progressive reduction in blood
      lactate levels at the end of training in both the exercised mice compared with
      controls (P=0.03 and P < 0.0001 for low-intensity and high-intensity exercise
      mice, respectively); in particular, blood lactate levels after high-intensity
      exercise were significantly lower than those measured in low-intensity exercise
      mice (P=0.0044). Immunoblotting analysis demonstrated that high-intensity
      exercise training produced a significant increase in the expression of
      mitochondrial enzymes contained within gastrocnemius and quadriceps muscles.
      These changes were associated with an increase in the amount of slow fibres in
      both these muscles of high-intensity exercise mice, as revealed by the counts of
      slow fibres stained with specific antibodies (P < 0.0001 for the gastrocnemius;
      P=0.0002 for the quadriceps). Our results demonstrate that high-intensity
      exercise, in addition to metabolic changes consisting of a decrease in blood
      lactate and body weight, induces an increase in the mitochondrial enzymes and
      slow fibres in different skeletal muscles of mice, which indicates an exercise
      induced increase in the aerobic metabolism. 

PMID- 24744503
TI  - Image chorioretinal vasculature in albino rats using photoacoustic
      ophthalmoscopy.
AB  - We imaged the microvascular network in both the retina and the choroid in an
      albino rat eye using photoacoustic ophthalmoscopy guided by optical coherence
      tomography. Relying on optical absorption and ultrasonic detection, photoacoustic
      ophthalmoscopy can image both retinal and choroidal vessel networks with high
      contrast.

PMID- 24744504
TI  - Enhancing the health-promoting effects of tomato fruit for biofortified food.
AB  - Consumption of tomato fruits, like those of many other plant species that are
      part of the human diet, is considered to be associated with several positive
      effects on health. Indeed, tomato fruits are an important source of bioactive
      compounds with known beneficial effects including vitamins, antioxidants, and
      anticancer substances. In particular, antioxidant metabolites are a group of
      vitamins, carotenoids, phenolic compounds, and phenolic acid that can provide
      effective protection by neutralizing free radicals, which are unstable molecules
      linked to the development of a number of degenerative diseases and conditions. In
      this review, we will summarize the recent progress on tomatoes nutritional
      importance and mechanisms of action of different phytochemicals against
      inflammation processes and prevention of chronic noncommunicable diseases (e.g.,
      obesity, diabetes, coronary heart disease, and hypertension). In addition, we
      will summarize the significant progress recently made to improve the nutritional
      quality of tomato fruits through metabolic engineering and/or breeding. 

PMID- 24744505
TI  - Could biomarkers of bone, cartilage or synovium turnover be used for relapse
      prediction in rheumatoid arthritis patients?
AB  - OBJECTIVE: The aim of this review is to clarify the usefulness of bone,
      cartilage, and synovial biomarker in the management of rheumatoid arthritis (RA)
      therapy in remission. SYNOVIAL BIOMARKERS: High MMP-3 levels are associated with
      joint progression in RA patients, but there is no data about their utility in
      clinical remission. IIINys and Glc-Gal-PYD seem to be more specific to synovium,
      but more studies are required. CARTILAGE BIOMARKERS: Unbalance between cartilage
      break-down biomarkers (urinary CTX II and COMP) and cartilage formation biomarker
      (PIIANP) was described. This unbalance is also associated with joint destruction
      and prognosis of destruction. No data are available on patients in remission.
      BONE BIOMARKERS: RA activity is correlated with an increase of bone resorption
      markers such as CTX I, PYD, and TRACP 5b and a decrease of bone formation markers
      such as OC and BALP. RA therapies seem to improve bone turnover in limiting bone
      resorption. There is no study about bone marker utility in remission. CONCLUSION:
      Biomarkers seem to correlate with RA activity and progression. They also could be
      used to manage RA therapies, but we need more data on RA remission to predict
      relapse.

PMID- 24744507
TI  - Duplicating research and befriending technology.

PMID- 24744508
TI  - Should low-dose computed tomography kidneys, ureter and bladder be the new
      investigation of choice in suspected renal colic?: A systematic review.
AB  - INTRODUCTION: Computed tomography kidneys, ureter and bladder (CTKUB) is the
      accepted gold standard investigation for suspected renal colic. Dose
      considerations are particularly pertinent in the context of detecting
      urolithiasis given the high risk of disease recurrence, which can necessitate
      multiple radiological examinations over the lifetime of a stone-former. We
      performed a systematic review of the literature to see whether there was any
      evidence that reducing the effective radiation dose of a CTKUB compromised the
      diagnostic accuracy of the scan. MATERIALS AND METHODS: Relevant databases
      including MedLine, EMBASE, DARE and the Cochrane Library were searched from
      inception to October 2012. All English language articles reporting on prospective
      studies where non-contrast, low-dose CT (LDCT) was used to investigate adults
      (males and non-pregnant females) presenting with flank pain or suspected
      urolithiasis were included. LDCT was defined as an effective radiation dose <3
      mSv per examination. RESULTS: Our initial search identified 497 records. After
      removing duplicates, 390 abstracts were screened, of which 375 were excluded,
      principally because outcomes of interest were not presented. Six papers remained
      for the final analysis, reporting on a total of 903 patients. Individual studies
      showed a prevalence of urolithiasis ranging between 36% and 88%, with additional
      pathologies found in 5-16%. The effective radiation dose of the LDCT techniques
      used ranged from 0.5 to 2.8 mSv. The sensitivity of LDCT for diagnosing stone
      disease was 90-97% with a specificity of 86-100%. CONCLUSIONS: The sensitivity
      and specificity of CTKUB for diagnosing urolithiasis remains high, even when the
      effective radiation dose is lowered. LDCT may miss some small stones (<3 mm),
      especially in obese patients (>30 kg/m(2)), but in this group LDCT still
      identifies most alternative diagnoses. With at least one level 1A and two level
      1B studies supporting the use of LDCT, there is Grade A recommendation for its
      use as the first-line investigation in suspected renal colic in non-obese
      patients.

PMID- 24744509
TI  - Is en-bloc transurethral resection of bladder tumor for non-muscle invasive
      bladder carcinoma better than conventional technique in terms of recurrence and
      progression?: A prospective study.
AB  - PURPOSE: Conventional, transurethral resection of bladder tumor (TURBT) involves
      piecemeal resection of the tumor and has a very high recurrence rate. We
      evaluated the outcome of en-bloc TURBT (ET) in comparison with conventional TURBT
      (CT) in non-muscle invasive bladder carcinoma in terms of recurrencew and
      progression. MATERIALS AND METHODS: From September 2007 to June 2011, in a
      prospective non-randomized interventional setting, ET was compared with CT in
      patients with solitary tumor of 2-4 cm size in terms of recurrence and
      progression. Pedunculated tumors, size >4 cm, tumors with associated
      hydroureteronephrosis and biopsy specimen with absent detrusor muscles were
      excluded. Fisher's exact test and survival analyses were used to compare the
      demography and the outcome. RESULTS: A total of 21 patients of ET were compared
      with 24 patients of CT. Mean tumor size was 2.8 cm in ET and 3.3 cm in CT group.
      Location of tumor, stage and grade were comparable in both groups. Recurrence
      rate was 28.6% versus 62.5% (P = 0.03) and progression rate was 19% versus 33.3%
      (P = 0.32) in ET versus CT group respectively. Recurrence free survival was 45.1
      (95% CI: 19.0-38 months) and 28.5 (95% CI: 35.4-54.7 months) in ET and CT group
      (P = 0.018). Progression free survival in ET and CT was 48.32 (95% CI: 35.5-53.0
      months) and 44.26 (95% CI: 39.0-57.5 months), P = 0.46. CONCLUSION: There was a
      significant reduction in the recurrence rate and time to recurrence with ET. Rate
      of progression was also relatively less with ET, though not statistically
      significant.

PMID- 24744506
TI  - Lysophosphatidic acid (LPA) signaling in human and ruminant reproductive tract.
AB  - Lysophosphatidic acid (LPA) through activating its G protein-coupled receptors
      (LPAR 1-6) exerts diverse cellular effects that in turn influence several
      physiological processes including reproductive function of the female. Studies in
      various species of animals and also in humans have identified important roles for
      the receptor-mediated LPA signaling in multiple aspects of human and animal
      reproductive tract function. These aspects range from ovarian and uterine
      function, estrous cycle regulation, early embryo development, embryo
      implantation, decidualization to pregnancy maintenance and parturition. LPA
      signaling can also have pathological consequences, influencing aspects of
      endometriosis and reproductive tissue associated tumors. The review describes
      recent progress in LPA signaling research relevant to human and ruminant
      reproduction, pointing at the cow as a relevant model to study LPA influence on
      the human reproductive performance. 

PMID- 24744510
TI  - A novel computer based stent registry to prevent retained stents: Will patient
      directed automated short message service and letter generator help?
AB  - OBJECTIVE: The objective of this study was to evaluate the feasibility of a
      computer based stent registry with patient directed automated information system
      to prevent retained double J stents. MATERIALS AND METHODS: A stent registry
      system was developed in collaboration with our Computerized Hospital Information
      Processing Service Department. This computer based stent registry with patient
      directed automated information system was integrated with the existing clinical
      work station. We reviewed the records retrospectively and assessed the
      feasibility of the system in reminding clinicians and patients regarding the
      stent and its date of removal. RESULTS: In a short run at our department, this
      new system appeared feasible, with patients promptly responding to the short
      message service and letter alerts. CONCLUSIONS: Computer based stent registry
      with patient directed automated information system is feasible in a clinical
      setting. A prospective study is needed for evaluation of its efficacy in
      preventing retained stents.

PMID- 24744511
TI  - Tumor doubling time of renal cell carcinoma measured by CT.
AB  - INTRODUCTION: Increasing numbers of patients are now being incidentally detected
      with small-sized renal cell carcinoma (RCC). The natural history of small renal
      masses is not completely understood. Currently, there are no specific tumor
      markers to determine initial risk or progression to metastatic disease. Growth
      rate and tumor size are factors shown to be predictive of tumor biology. In this
      study, we attempted to examine the natural history of RCC and calculated the
      doubling times (DTs) of untreated RCC at the primary site. MATERIALS AND METHODS:
      We retrospectively reviewed the records of all patients with RCC who had at least
      two measurements of the same tumor mass obtained on computed tomography (CT)
      imaging on two different dates (at least 6 months apart) during periods of non
      treatment. The tumor volume was calculated at two points in time using images
      yielded by the CT imaging. The tumor DT was calculated using the following
      equation: DT = (T - T0) * log2/logV - logV0. RESULTS: Twenty-two (13 male and
      nine female) patients with ages ranging from 32 to 71 years (mean 52.22 years)
      were included in the study. The initial maximum tumor diameter ranged from 2.8 to
      6.8 cm (mean 3.93 cm) and the last maximum tumor diameter ranged from 3.2 to 7.8
      cm (mean 4.39 cm). The DT for the entire population was 460.01 days (range 174
      913 days). CONCLUSIONS: RCC is a diverse disease process, with the majority of
      lesions demonstrating malignant disorder. In our study, the DT for the patient
      population was 460.01 days (range 174-913 days).

PMID- 24744512
TI  - Predictors of nephrectomy in high grade blunt renal trauma patients treated
      primarily with conservative intent.
AB  - INTRODUCTION: There is no consensus on the optimal management of high grade renal
      trauma. Delayed surgery increases the likelihood of secondary hemorrhage and
      persistent urinary extravasation, whereas immediate surgery results in high renal
      loss. Hence, the present study was undertaken to evaluate the predictors of
      nephrectomy and outcome of high Grade (III-V) renal injury, treated primarily
      with conservative intent. MATERIALS AND METHODS: The records of 55 patients who
      were admitted to our institute with varying degrees of blunt renal trauma from
      January 2005 to December 2012 were retrospectively reviewed. Grade III-V renal
      injury was defined as high grade blunt renal trauma and was present in 44
      patients. The factors analyzed to predict emergency intervention were demographic
      profile, grade of injury, degree of hemodynamic instability, requirement of blood
      transfusion, need for intervention, mode of intervention, and duration of
      intensive care unit stay. RESULTS: Rest of the 40 patients with high grade injury
      (grade 3 and 4)did not require emergency intervention and underwent a trail of
      conservative management. 7 of the 40 patients with high grade renal injury (grade
      3 and 4), who were managed conservatively experienced complications requiring
      procedural intervention and three required a delayed nephrectomy. Presence of
      grade V injuries with hemodynamic instability and requirement of more than 10
      packed cell units for resuscitation were predictors of nephrectomy. Predictors of
      complications were urinary extravasation and hemodynamic instability at
      presentation. CONCLUSION: Majority of the high grade renal injuries can be
      successfully managed conservatively. Grade V injuries and the need for more
      packed cell transfusions during resuscitation predict the need for emergency
      intervention.

PMID- 24744513
TI  - Anderson-Hynes pyeloplasty with isthmotomy and lateropexy in horseshoe kidneys
      with pelviureteric junction obstruction in children.
AB  - OBJECTIVE: The objective of this study was to evaluate the results of Anderson
      Hynes pyeloplasty with isthmotomy and lateropexy in horseshoe kidney with
      pelviureteric junction obstruction (PUJO). MATERIALS AND METHODS: Medical records
      of patients of horseshoe kidney with PUJO operated in our institute between June
      1998 and June 2012 were reviewed. Anderson-Hynes pyeloplasty with isthmotomy and
      lateropexy was performed in all patients. The surgical outcome was evaluated with
      emphasis on the changes in degree of hydronephrosis by ultrasonography, renal
      drainage and function assessed by diuretic renal scans. RESULTS: We studied the
      records of eight children of horseshoe kidney having unilateral PUJO. Obstruction
      was caused by a crossing lower-pole vessel in two cases, a high ureteral
      insertion in three and narrowing of the PUJ in three cases. Post-operative follow
      up (median 4.4 years, range 18 months to 10 years) revealed improved renal
      function and good drainage in all cases. Hydronephrosis disappeared in 3, 4
      showed Grade 1 and one showed Grade 2 hydronephrosis. All children are doing well
      and have no symptoms. CONCLUSION: Anderson-Hynes pyeloplasty with isthmotomy and
      lateropexy is a highly effective and safe procedure for treating PUJO in
      horseshoe kidney in children.

PMID- 24744514
TI  - The significance of sperm heads and tails within the vasal fluid during vasectomy
      reversal.
AB  - INTRODUCTION: The finding of only sperm heads and/or short tails (SHST) during
      vasectomy reversal (VR) creates a difficult decision for the best method of vasal
      reconstruction, i.e. vasovasostomy (VV) or epididymovasostomy (EV). Using outcome
      analyses, we report the impact of SHST alone and combined with qualitative
      analysis of gross fluid quality in predicting successful VR. MATERIALS AND
      METHODS: The records of 356 men who underwent VR by a single surgeon from 2005 to
      2012 were retrospectively reviewed. Intravasal fluid was assessed for gross
      quality (i.e., clear, opaque, pasty or creamy) as well as microscopic composition
      (i.e., motile or non-motile whole sperm, SHST or no sperm). The post-operative
      patency rates and semen analysis parameters were assessed. RESULTS: Fourteen men
      (3.9%) demonstrated SHST bilaterally in the vasal fluid. The median duration from
      vasectomy was 6.0 years (interquartile range 4.0-9.8). Bilateral VVs were
      performed on 12 men (86%), while two men (14%) had a unilateral VV and a
      contralateral EV. Of the 26 vasa undergoing VR, the majority of the fluid quality
      was classified as creamy (n = 20 vasa, 76.9%). The remaining fluid was classified
      as pasty (n = 3 vasa, 11.5%), opaque (n = 2 vasa, 7.7%) and clear (n = 1 vasa,
      3.8%). In cases undergoing bilateral VV with only SHST, patency rates were 90.9%,
      and both cases of unilateral EV were patent (100%). CONCLUSIONS: VV was
      successful in 90.9% of patients undergoing VR in the setting of SHST alone. Even
      when creamy or pasty fluid was present, the results surpassed the expected
      patency rate for an EV. Therefore, the presence of only SHST, regardless of fluid
      quality, should not dissuade the surgeon from performing a VV. CONCLUSIONS: VV
      was successful in 90.9% of patients undergoing VR in the setting of SHST alone.
      Even when creamy or pasty fluid was present, the results surpassed the expected
      patency rate for an EV. Therefore, the presence of only SHST, regardless of fluid
      quality, should not dissuade the surgeon from performing a VV.

PMID- 24744515
TI  - BPH management today.

PMID- 24744516
TI  - Epidemiology and etiology of benign prostatic hyperplasia and bladder outlet
      obstruction.
AB  - Benign prostatic hyperplasia (BPH) is a histological diagnosis associated with
      unregulated proliferation of connective tissue, smooth muscle and glandular
      epithelium. BPH may compress the urethra and result in anatomic bladder outlet
      obstruction (BOO); BOO may present as lower urinary tract symptoms (LUTS),
      infections, retention and other adverse events. BPH and BOO have a significant
      impact on the health of older men and health-care costs. As the world population
      ages, the incidence and prevalence of BPH and LUTS have increased rapidly.
      Although non-modifiable risk factors - including age, genetics and geography -
      play significant roles in the etiology of BPH and BOO, recent data have revealed
      modifiable risk factors that present new opportunities for treatment and
      prevention, including sex steroid hormones, the metabolic syndrome and
      cardiovascular disease, obesity, diabetes, diet, physical activity and
      inflammation. We review the natural history, definitions and key risk factors of
      BPH and BOO in epidemiological studies. 

PMID- 24744517
TI  - Assessment of BPH/BOO.
AB  - The assessment of men with bladder outflow obstruction relies on an adequate
      history and examination. Uroflowmetry and post-void residue estimation are very
      revealing and may be sufficient in the majority of men. The prostate-specific
      antigen test may be used to select men who are at a high risk of progression. In
      specific situations, cystometry may be required. We discuss the use of cystometry
      and the newer less-invasive methods of assessment that have emerged over the last
      few years, including ultrasound estimation of intravesical prostatic protrusion,
      prostatic urethra angle, detrusor wall thickness, ultrasound-estimated bladder
      weight, near-infrared spectroscopy and the condom catheter and penile cuff tests.
      Although these techniques show promise, they still require further modifications,
      standardization and testing in larger populations. In addition, they should be
      used in men where only specific questions need to be answered. 

PMID- 24744519
TI  - Hormonal manipulation of lower urinary tract symptoms secondary to benign
      prostatic obstruction.
AB  - Although the etiology of lower urinary tract symptoms (LUTS) is often
      multifactorial, a significant proportion of men over the age of 50 suffer from
      benign prostatic obstruction (BPO) secondary to benign prostatic hyperplasia.
      Prostate, being an androgen responsive organ is dependent on the male sex
      hormone, testosterone, for growth. Thus, treatment strategies that manipulate the
      levels of circulating hormones that influence the level of testosterone and/or
      prostatic growth represent an important potential option for patients suffering
      with troublesome LUTS due to BPO. Despite this, the only hormonal treatment that
      is currently used in daily clinical practice is the 5-alpha reductase inhibitor.
      In this article, we review the current evidence on the use of the 5-alpha
      reductase inhibitors finasteride and dutasteride. We also discuss new emerging
      hormonal manipulation strategies for patients with LUTS secondary to BPO. 

PMID- 24744518
TI  - Pharmacology of the lower urinary tract.
AB  - Pharmacology of the lower urinary tract provides the basis for medical treatment
      of lower urinary tract symptoms (LUTS). Therapy of LUTS addresses obstructive
      symptoms (frequently explained by increased prostate smooth muscle tone and
      prostate enlargement) in patients with benign prostate hyperplasia (BPH) and
      storage symptoms in patients with overactive bladder (OAB). Targets for medical
      treatment include G protein-coupled receptors (alpha1-adrenoceptors, muscarinic
      acetylcholine receptors, beta3-adrenoceptors) or intracellular enzymes (5alpha
      reductase; phosphodiesterase-5, PDE5). Established therapies of obstructive
      symptoms aim to induce prostate smooth muscle relaxation by alpha1-blockers or
      PDE5 inhibitors, or to reduce prostate growth and volume with 5alpha-reductase
      inhibitors. Available options for treatment of OAB comprise anitmuscarinics,
      beta3-adrenoceptor agonists, and botulinum toxin A, which improve storage
      symptoms by inhibition of bladder smooth muscle contraction. With the recent
      approval of beta3-antagonists, PDE inhibitors, and silodosin for therapy of LUTS,
      progress from basic research of lower urinary tract pharmacology was translated
      into new clinical applications. Further targets are in preclinical stages of
      examination, including modulators of the endocannabinoid system and transient
      receptor potential (TRP) channels. 

PMID- 24744520
TI  - Non-Hormonal treatment of BPH/BOO.
AB  - OBJECTIVES: To review the use of non-hormonal pharmacotherapies in the treatment
      of lower urinary tract symptoms (LUTS) due to presumed benign prostatic
      hyperplasia (BPH). MATERIALS AND METHODS: A search of the PUBMED database was
      conducted for the terms BPH, LUTS, bladder outlet obstruction, alpha-adrenoceptor
      blockers, anti-muscarinics, and phosphodiesterase-5-inhibitors. RESULTS: Medical
      therapy has long been established as the accepted standard of care in the
      treatment of male LUTS. The aim of treatment is improvement in symptoms and
      quality of life whilst minimizing adverse effects. The agents most widely used as
      1(st) line therapy are alpha-blockers (AB), as a standalone or in combination
      with 2 other classes of drug; 5-alpha reductase inhibitors and anti-muscarinics.
      AB have rapid efficacy, improving symptoms and flow rate in a matter of days,
      these effects are then maintained over time. AB do not impact on prostate size
      and do not prevent acute urinary retention or the need for surgery. Anti
      mucarinics, alone or in combination with an AB are safe and efficacious in the
      treatment of bothersome storage symptoms associated with LUTS/BPH.
      Phosphodiesterase-5 inhibitors are an emerging treatment option that improve LUTS
      without improving flow rates. CONCLUSIONS: AB are the most well-established
      pharmacotherapy in the management of men with LUTS/BPH. The emergence of
      different classes of agent offers the opportunity to target underlying
      pathophysiologies driving symptoms and better individualize treatment.

PMID- 24744521
TI  - Surgical therapy for benign prostatic hypertrophy/bladder outflow obstruction.
AB  - Monopolar transurethral resection of the prostate (TURP) with endoscopic
      electrocautery remains the gold standard surgical technique for benign prostatic
      hypertrophy (BPH) by which all new procedures are compared. We reviewed the
      current literature, and international urological guidelines and consensus opinion
      on various surgical options for BPH and present a brief overview of alternative
      techniques including bipolar TURP, transurethral incision of the prostate,
      transurethral vaporization of the prostate, laser prostatectomy (with holmium,
      thulium and potassium titanyl phosphate greenlight lasers) and open prostatectomy
      (with mention of new techniques including laparoscopic and robotic
      prostatectomy). Emerging, experimental and less established techniques are also
      described including endoscopic heat generation (transurethral microwave
      thermotherapy, radiofrequency transurethral needle ablation of the prostate, high
      intensity focused ultrasound, hot water induced thermotherapy, pulsed
      electromagnetic radiofrequency), injection therapy (transurethral ethanol
      ablation and botulinum toxin) and mechanical devices (intraprostatic stents and
      urethral lift devices). Despite a plethora of surgical options, none have
      realistically improved outcomes in the long-term compared with TURP. Improvements
      have been made on improving surgical morbidity and time in hospital. Questions
      remain in this area, including what specific elements of bladder outflow
      obstruction (BOO) result in damage to the urinary tract, how does BPH contribute
      to BOO and how much prostate volume reduction is necessary to relieve BOO or
      lower urinary tract symptoms. Given these unanswered questions and the multitude
      of procedures available, it is clear that appropriate counselling is necessary in
      all men who undergo BPH surgery. 

PMID- 24744522
TI  - Management of the complications of BPH/BOO.
AB  - Most men will develop histological BPH if they live long enough. Approximately,
      half will develop benign prostatic enlargement (BPE) and about half of these will
      get BOO with high bladder pressures and low flow, this in turn leads to detrusor
      wall hypertrophy. Many of these men will only have lower urinary tract symptoms
      (LUTS) but a significant number will also suffer the other complications of BPH.
      These include urinary retention (acute and chronic), haematuria, urinary tract
      infection, bladder stones, bladder wall damage, renal dysfunction, incontinence
      and erectile dysfunction. Recognition of the complications of BPH/BOO early
      allows more effective management of these complications. This is particularly
      important for the more serious urinary infections and also for high-pressure
      chronic retention (HPCR). Complications of LUTS/BPH are very rare in clinical
      trials because of their strict inclusion and exclusion criteria but are more
      common in real life practice. 

PMID- 24744523
TI  - BPH and prostate cancer risk.
AB  - INTRODUCTION: With the exclusion of non-melanomatous skin malignancy, prostate
      cancer (PCa) is the second most prevalent cancer in men globally. It has been
      reported that the majority of men will develop benign prostatic hyperplasia (BPH)
      by the time they reach their 60s. Together, these prostatic diseases have a
      significant morbidity and mortality affecting over a billion men throughout the
      world. The risk of developing prostate cancer of men suffering BPH is one that
      has resulted in a healthy debate amongst the urological community. Here, we try
      to address this conundrum with clinical and basic science evidence. MATERIALS AND
      METHODS: Data from an online search and contemporary data presented at
      international urological congresses was reviewed. RESULTS: BPH and PCa can be
      linked together at a molecular and cellular level on genetic, hormonal, and
      inflammatory platforms suggesting that these prostatic diseases have common
      pathophysiological driving factors. Epidemiological studies are weighted towards
      the presence of BPH having a greater risk for a man to develop PCa in his
      lifetime; however, a conclusion of causality cannot be confidently stated.
      CONCLUSION: The future workload healthcare practitioners will face regarding BPH,
      and PCa will substantially increase. Further basic science and large
      epidemiological studies using a global cohort of men are required prior to the
      urological community confidently counseling their patients with BPH with regards
      to their PCa risk.

PMID- 24744524
TI  - Virilizing lipoadenoma of the adrenal gland in a pre-pubertal girl: A rare case.
AB  - We report a case of a 12-year-old girl who presented with the history of
      hirsutism. On evaluation, she was found to have testosterone secreting adrenal
      gland tumor. Histopathological examination of the adrenalectomy specimen revealed
      a lipoadenoma. 

PMID- 24744525
TI  - Ureteral spread of a primary cutaneous diffuse large B-cell lymphoma, leg type.
AB  - We report a case of 76-year-old man, with a past medical history of primary
      cutaneous diffuse large B-cell lymphoma, leg type (PCDLBCL-LT), who presented
      with ureteral tumor diagnosed as urothelial carcinoma on imaging investigations.
      Histological examination showed an unusual finding. The tumor was a ureteral
      localization of the PCDLBCL-LT previously diagnosed. To the best of our
      knowledge, this is the first case of PCDLBCL-LT with ureteral spread described in
      the literature. 

PMID- 24744526
TI  - Mesenchymal chondrosarcoma of kidney.
AB  - Mesenchymal chondrosarcoma of the kidney is a very rare entity with no definite
      treatment protocol. Herein, we describe one such case with discussion of its
      diagnosis and management. The patient had a well circumscribed mass in right
      kidney extending into the inferior vena cava and metastasis to both the lungs.
      Right nephrectomy was performed and the histopathological examination confirmed
      the diagnosis to be renal mesenchymal chondrosarcoma. After surgical removal of
      the tumor, the patient was given chemotherapy with Cisplatin and Epirubicin,
      following which there was significant regression of lung nodules. 

PMID- 24744527
TI  - Appendicocalicostomy: A case of mistaken identity.
AB  - Anatomical structures with similar appearance may at times be confused for each
      other. This situation can be compounded by lack of normal anatomical planes. We
      did ureterocalicostomy on a 32-year-female with secondary pelvi-ureteral junction
      obstruction. Post-operatively, it was discovered that she had a long appendix
      running parallel to ureter in retroperitoneum, which was misidentified as ureter
      and anastomosed to the lower pole of the kidney. She was re-explored, appendix
      was removed, ureter was identified and ureterocalicostomy was done. Patient is
      asymptomatic at 1 year follow-up. 

PMID- 24744528
TI  - Keratinizing squamous metaplasia of the upper urinary tract in a child with a
      solitary kidney.
AB  - We report a rare case of keratinizing squamous metaplasia of the upper urinary
      tract in a child with a single kidney. Squamous metaplasia has rarely been
      reported in the upper urinary tract, and is even rarer in children. 

PMID- 24744529
TI  - Supernumerary testis: Imaging appearance of a rare entity.
AB  - Supernumerary testis is a rare congenital anomaly of the testis arising from
      abnormal division in the genital ridge during the embryogenesis of testis. We
      describe a case of polyorchidism detected incidentally in a 52-year-old with
      renal failure. 

PMID- 24744530
TI  - L.I.F.T. study: Prostatic urethral lift for the treatment of LUTS associated with
      BPH.

PMID- 24744531
TI  - Pseudotumor of urinary bladder by infected hernia mesh: Where is the evidence of
      infection?

PMID- 24744532
TI  - Learning to think creatively and critically!

PMID- 24744533
TI  - Piece meal research.

PMID- 24744534
TI  - Flying high!!!

PMID- 24744535
TI  - Dengue and acute gingival bleeding.

PMID- 24744536
TI  - Can MTA be: Miracle trioxide aggregate?
AB  - Mineral trioxide aggregate (MTA) has been used for more than 10 years in the
      dental community and has often been thought of as a material of choice for the
      endodontist. The dental pulp is closely related to periodontal tissues through
      apical foramina, accessory canals, and dentinal tubules. Due to this
      interrelationship, pulpal diseases may influence periodontal health and
      periodontal infections may affect pulpal integrity. It is estimated that pulpal
      and periodontal problems are responsible for more than 50% of tooth mortality.
      Thus, these associations recommend an interdisciplinary approach. MTA appears to
      exhibit significant results even in periodontal procedures as it is the first
      restorative material that consistently allows for over-growth of cementum and may
      facilitate periodontal tissue regeneration. Thus, in the present review, an
      attempt is made to discuss the clinical applications of MTA as an
      interdisciplinary approach. 

PMID- 24744537
TI  - Microbial role in periodontitis: Have we reached the top? Some unsung bacteria
      other than red complex.
AB  - The microbial etiology of periodontal disease has been the focus of researchers
      for a long time. The search for the pathogens of periodontal diseases has been
      underway for more than 100 years, and continues up today. Despite the increasing
      knowledge about oral microbiota, we are not able to implicate any one particular
      organism that can be considered as a candidate pathogen. In fact the term
      "candidate pathogen" has lost its steam with a myriad of microorganisms being
      incriminated from time to time. Most studies of the bacterial etiology of
      periodontitis have used either culture-based or targeted deoxyribonucleic acid
      approaches and so it is likely that pathogens remain undiscovered. The advent of
      16S cloning and sequencing has facilitated identification of several uncultivable
      bacteria in the oral cavity. The concept that not one single organism, but
      several organisms contained in the biofilm orchestrating in a medley of the show
      appears to be more plausible. The present review highlights some lesser known
      bacteria associated with periodontal destruction. 

PMID- 24744538
TI  - Framingham cardiovascular risk in patients with obesity and periodontitis.
AB  - BACKGROUND: Obesity is a chronic inflammatory condition that has been associated
      to a risk factor for the development of periodontitis and cardiovascular disease;
      however, the relationship still needs to be clarified. The objective of this
      study was to evaluate the cardiovascular risk in obese patients with chronic
      periodontitis. MATERIALS AND METHODS: A total of 87 obese patients were evaluated
      for anthropometric data (body mass index [BMI], waist circumference, body fat),
      systolic blood pressure (SBP) and diastolic blood pressure (DBP), cholesterol,
      high-density lipoprotein (HDL) and low-density lipoprotein (LDL), triglycerides,
      glycemia and periodontal parameters (visible plaque index (VPI), gingival
      bleeding index (GBI), bleeding on probing (BOP), periodontal probing depth (PPD)
      and clinical attachment level (CAL)). RESULTS: PATIENTS WERE DIVIDED INTO TWO
      GROUPS ACCORDING TO THE PERIODONTAL CHARACTERISTICS FOUND: Group O-PD: Obese
      patients with chronic periodontitis (n = 45), 22 men and 23 women; and Group O
      sPD: Obese patients without chronic periodontitis (n = 42), 17 men and 25 women.
      Patients had a BMI mean of 35.2 (+/-5.1) kg/m(2) . Group O-PD showed a similarity
      between the genders regarding age, SBP, DBP, cholesterol, HDL, GBI, VPI, PPD >=4
      mm and CAL >=4 mm. O-PD women showed greater glycemia level and smoking
      occurrence, but O-PD men presented a 13% - risk over of developing coronary
      artery disease in 10 years than O-PD women, 9% - risk over than O-sPD men and 15%
      - risk over than O-sPD women, by the Framingham Score. CONCLUSIONS: It was
      concluded that obesity and periodontal disease are cardiovascular risk factors
      and that the two associated inflammatory conditions potentially increases the
      risk for heart diseases.

PMID- 24744539
TI  - Interrelationship between chronic periodontitis and anemia: A 6-month follow-up
      study.
AB  - BACKGROUND: In India, anemia is a common and serious health disorder among both
      sexes and all age groups, with anemia of chronic disease (ACD) being the second
      most prevalent anemia. Periodontitis is an inflammatory disease of the supporting
      tissues of the tooth caused by specific microorganisms. An immune response to
      bacteria and their products induces a major vascular response, offering
      explanatory mechanisms for the interactions between periodontal infection and a
      variety of systemic disorders. Therefore, periodontitis results in low-grade
      systemic inflammation, which may cause lower number of erythrocytes and,
      consequently, lower hemoglobin concentration. MATERIALS AND METHODS: A total of
      100 systemically healthy male patients visiting the outpatient department
      participated in the study. Of these, 50 patients had healthy periodontium and 50
      patients had chronic periodontitis. Clinical parameters and red blood cell
      parameters of all the patients were assessed at baseline and 6 months after non
      surgical periodontal therapy. Statistical analysis using Student's t-test was
      performed. RESULTS: Data analysis revealed that patients with chronic
      periodontitis showed an improvement in both clinical and red blood cell
      parameters from baseline to 6 months after non-surgical periodontal therapy.
      CONCLUSION: From the present study, it can be concluded that like any other
      chronic condition, chronic periodontitis can lead to ACD. It also provides
      evidence that non-surgical periodontal therapy can improve the anemic status of
      patients with chronic periodontitis.

PMID- 24744540
TI  - Fluorosed fibroblast attachment on fluorosed and nonfluorosed teeth after SRP and
      EDTA root biomodification.
AB  - BACKGROUND: Fluorosis causes mineralization changes in the tooth and can lead to
      morphologic alterations of fibroblasts. To understand the effect of fluorosis on
      periodontal healing, the initial step during healing, such as fibroblast
      attachment to the root surface, needs to be evaluated. Hence, the objective of
      the present study was to study the attachment of fluorosed fibroblasts on the
      fluorosed and nonfluorosed root fragments. MATERIALS AND METHODS: A total of 56
      fluorosed and nonfluorosed, periodontally healthy and diseased tooth roots were
      obtained and allotted to eight groups: Fluorosed and nonfluorosed healthy
      controls (FH and NFH, respectively), fluorosed and nonfluorosed diseased controls
      (FD and NFD, respectively), fluorosed and nonfluorosed roots treated with scaling
      and root planing (FD + S and NFD + S, respectively), and similar groups treated
      with scaling and root planing and 24% ethylenediaminetetraacetic acid (EDTA) gel
      application for 2 min (FD + SE and NFD + SE, respectively). After the respective
      treatment, the root fragments were incubated in the human periodontal ligament
      fibroblast cells obtained and cultured from freshly extracted healthy human
      fluorosed premolar tooth root. RESULTS: In the nonfluorosed roots category,
      greater attachment was found in the untreated nonfluorosed diseased (P = 0.036)
      and SRP-treated nonfluorosed diseased groups (P = 0.008) as compared to the
      nonfluorosed healthy group. While in the fluorosed roots category, no significant
      difference was observed in FL-FA (P > 0.05) within the group. However, no
      attachment was observed in EDTA-treated fluorosed root fragments. When fluorosed
      groups were compared to nonfluorosed groups, no significant changes were noted
      between the groups. CONCLUSION: SRP proves to be a standard requirement for
      fibroblast attachment to occur both in fluorosed and nonfluorosed roots. Although
      there was no significant difference in attachment between SRP and SRP + EDTA
      among fluorosed roots, EDTA does not seem to be a promising agent for root
      biomodification in fluorosed roots in a given concentration and time of
      treatment.

PMID- 24744541
TI  - Effect of citric acid, tetracycline, and doxycycline on instrumented
      periodontally involved root surfaces: A SEM study.
AB  - BACKGROUND: A surface smear layer consisting of organic and inorganic material is
      formed on the root surface following mechanical instrumentation and may inhibit
      the formation of new connective tissue attachment to the root surface.
      Modification of the tooth surface by root conditioning has resulted in improved
      connective tissue attachment and has advanced the goal of reconstructive
      periodontal treatment. AIM: The aim of this study was to compare the effects of
      citric acid, tetracycline, and doxycycline on the instrumented periodontally
      involved root surfaces in vitro using a scanning electron microscope. SETTINGS
      AND DESIGN: A total of 45 dentin samples obtained from 15 extracted, scaled, and
      root planed teeth were divided into three groups. MATERIALS AND METHODS: The root
      conditioning agents were applied with cotton pellets using the Passive burnishing
      technique for 5 minutes. The samples were then examined by the scanning electron
      microscope. STATISTICAL ANALYSIS USED: The statistical analysis was carried out
      using Statistical Package for Social Sciences (SPSS Inc., Chicago, IL, version
      15.0 for Windows). For all quantitative variables means and standard deviations
      were calculated and compared. For more than two groups ANOVA was applied. For
      multiple comparisons post hoc tests with Bonferroni correction was used. RESULTS:
      Upon statistical analysis the root conditioning agents used in this study were
      found to be effective in removing the smear layer, uncovering and widening the
      dentin tubules and unmasking the dentin collagen matrix. CONCLUSION: Tetracycline
      HCl was found to be the best root conditioner among the three agents used.

PMID- 24744542
TI  - Reliability study of Mahajan's classification of gingival recession: A pioneer
      clinical study.
AB  - BACKGROUND: Gingival recession defects (GRD) are one of the most commonly
      encountered conditions for which periodontal treatment is required. Several
      attempts have been made to classify GRD. Among all the classifications Millers
      classification for gingival recessions is the most accepted. Recently, several
      limitations and drawbacks have been pointed out in Miller's classification
      system. The aim of the present study is to test the reliability of the recently
      proposed Mahajan's Modification of the Miller's Classification for GRD. MATERIALS
      AND METHODS: All 15 males and 11 females between the ages of 22 and 55 years
      (mean age, 37.15 year) with at least one buccal gingival recession were
      consecutively recruited by the same periodontist in order to test the reliability
      of the new classification of GRD. The classification was tested by two examiners
      blinded to the data collected by the other examiner. Intra-rater and inter-rater
      agreement was assessed. RESULTS: The new classification system of gingival
      recessions was tested in a total of 175 gingival recessions in 26 patients. The
      intraclass correlation coefficient for inter-rater agreement was 0.90, showing an
      almost perfect agreement between the examiners. CONCLUSION: The newly proposed
      classification system eliminates the drawbacks and limitations associated with
      Miller's classification system and can be used to classify GRD reliably.

PMID- 24744543
TI  - Analysis of the gingival biotype based on the measurement of the dentopapillary
      complex.
AB  - BACKGROUND: The gingival morphology of the maxillary anterior region plays an
      important role in determining the final esthetic outcome. Knowledge of the
      periodontal biotype is of fundamental importance because the anatomical
      characteristics of the periodontium, such as gingival thickness, gingival width
      and alveolar bone morphology, will determine periodontium behavior when submitted
      to physical, chemical, or bacterial injury or during periodontal or implant
      surgical procedures and orthodontic treatment. MATERIALS AND METHODS: 50 subjects
      with healthy periodontal tissues with no loss of attachment and (b) presence of
      all anterior teeth in both upper and lower jaw were selected. On clinical
      examination gingival thickness was recorded based on the transparency of
      periodontal probe. Following parameters are recorded from dental cast, i.e.,
      crown length, crown width, papillary length (PL) and papillary width. RESULTS:
      There was highly significant correlation between gingival biotype and crown
      length and area of papilla with P value -0.002 and 0.013 respectively.
      Significant correlation was found between area of crown and PL with P value 
      0.013 and 0.016. The results of discriminant function analysis showed that
      average crown length was the best single determinant of biotype and area of
      papilla was the next best choice. CONCLUSION: Within the limits of the current
      investigation, the existence and correlation of different gingival biotypes and
      dentopapillary complex dimension has been confirmed. These findings can be
      utilized as objective guidelines for determining the biotype and response of
      gingiva to many dental operative procedures.

PMID- 24744544
TI  - Evaluation of antiplaque and antigingivitis effect of herbal mouthwash in
      treatment of plaque induced gingivitis: A randomized, clinical trial.
AB  - BACKGROUND: Ayurvedic drugs have been used since ancient times to treat diseases
      including periodontal diseases. Oral rinses made from ayurvedic medicines are
      used in periodontal therapy to control bleeding and reduce inflammation. The aim
      of this clinical study is to verify the efficacy of herbal mouthwash containing
      Pilu, Bibhitaka, Nagavalli, Gandhapura taila, Ela, Peppermint satva, and Yavani
      satva on reduction of plaque and gingivitis. MATERIALS AND METHODS: A total of
      100 volunteers with clinical signs of mild to moderate gingivitis were selected
      and assigned to Group A (only scaling done) and Group B (scaling along with the
      use of herbal mouthwash). After recording the clinical parameters, the patients
      were instructed to use herbal mouthwash 15 ml for 30 s twice daily after food in
      Group B and oral hygiene instructions were given to all patients. Plaque and
      gingivitis assessment were carried out using the plaque index (Silness nd Loe,
      1964), Gingival index (Loe And Silness, 1963), Gingival bleeding index (Ainamo
      and Bay, 1975) at baseline and at 21 days of the herbal mouthwash use.
      Statistically analysis was carried out using the student's t-test for normally
      distributed data and Wilcoxson test or Mann-Whitney U-test for skewed data.
      RESULTS: Our results showed that herbal mouthwash was effective in treatment of
      plaque induced gingivitis in Group B when compared with the Group A. CONCLUSION:
      Herbal mouthwash is effective in treatment of plaque induced gingivitis and can
      be effectively used as an adjunct to mechanical therapy with lesser side-effects.

PMID- 24744546
TI  - Comparative evaluation of the efficacy of the cyclooxygenase pathway inhibitor
      and nitric oxide synthase inhibitor in the reduction of alveolar bone loss in
      ligature induced periodontitis in rats: An experimental study.
AB  - BACKGROUND: Alveolar bone loss is the most striking feature of periodontal
      disease. The aim of this study was to investigate the effect of a cyclooxygenase
      (COX) pathway inhibitor and nitric oxide synthase (NOS) inhibitor in the
      reduction of alveolar bone loss in an experimental periodontal disease (EPD)
      model. MATERIALS AND METHODS: The study was conducted on 60 Wistar rats divided
      into three groups of 20 rats each and then subjected to a ligature placement
      around the left maxillary second molars. Group 1 rats were treated with COX
      inhibitor (diclofenac sodium 10 mg/kg/d), group 2 with NOS inhibitor
      (aminoguanidine hydrochloride 10 mg/kg/d) and group 3 served as controls,
      receiving only saline, intraperitoneally 1h before EPD induction and daily until
      the sacrifice on the 11(th) day. Leukogram was performed before ligation, at 6 h
      and at the first, seventh and 11(th) days after EPD induction. After sacrifice,
      all the excised maxillae were subjected to morphometric and histometric analysis
      to measure the alveolar bone loss. Histopathological analysis was carried out to
      estimate cell influx, alveolar bone and cementum integrity. RESULTS: Induction of
      experimental periodontitis in the rat model produced pronounced leucocytosis,
      which was significantly reduced by the administration of diclofenac sodium and
      aminoguanidine on the 11(th) day. In morphometric and histometric examinations,
      both the test drugs significantly (P < 0.05) inhibited the alveolar bone loss as
      compared with the control group. CONCLUSION: Both COX inhibitor and NOS inhibitor
      are equally effective in inhibiting the inflammatory bone resorption in an
      experimental periodontitis model.

PMID- 24744545
TI  - To estimate salivary aspartate aminotransferase levels in chronic gingivitis and
      chronic periodontitis patients prior to and following non-surgical periodontal
      therapy: A clinico-biochemical study.
AB  - CONTEXT: Saliva can be used as a diagnostic fluid in dentistry. Various enzymes
      have been proposed as markers for periodontal destruction. One of them is
      aspartate aminotransferase, for which salivary analysis can offer a cost
      effective approach for monitoring the disease. Changes in enzymatic activity
      reflect metabolic changes in the gingiva and periodontium in inflammation. AIMS:
      The purpose of this study was to assess the aspartate aminotransferase levels in
      saliva prior to and following scaling and root planning (SRP) at 1 month and 3
      month interval and correlating it with the clinical parameters in generalized
      chronic gingivitis and chronic periodontitis patients. MATERIALS AND METHODS:
      Thirty patients with generalized chronic gingivitis and 30 with generalized
      chronic periodontitis were selected. The activity of aspartate aminotransferase
      levels in saliva were assessed biochemically before and after SRP at 1 month and
      3 months. The aspartate aminotransferase levels were correlated with clinical
      parameters (gingival index and probing depth). STATISTICAL ANALYSIS USED: A
      paired t test was done. RESULTS: A decrease in gingival index, probing depth, and
      aspartate aminotransferase levels were seen in both the groups at 1 and 3 months
      which was found to be statistically highly significant (P value 0.00). Aspartate
      aminotransferase levels were statistically significantly correlated with the
      clinical parameters at baseline (P < 0.05) but at 3 months, a positive
      correlation was seen in both the groups which was statistically insignificant (P
      > 0.05). CONCLUSIONS: Elevated salivary aspartate aminotransferase levels were
      seen in generalized chronic gingivitis and chronic periodontitis patients, with
      higher values recorded in generalized chronic periodontitis correlating to the
      tissue destruction taking place in these conditions.

PMID- 24744547
TI  - Cognition, comprehension and application of biostatistics in research by Indian
      postgraduate students in periodontics.
AB  - BACKGROUND: Biostatistics is an integral part of research protocols. In any field
      of inquiry or investigation, data obtained is subsequently classified, analyzed
      and tested for accuracy by statistical methods. Statistical analysis of collected
      data, thus, forms the basis for all evidence-based conclusions. AIM: The aim of
      this study is to evaluate the cognition, comprehension and application of
      biostatistics in research among post graduate students in Periodontics, in India.
      MATERIALS AND METHODS: A total of 391 post graduate students registered for a
      master's course in periodontics at various dental colleges across India were
      included in the survey. Data regarding the level of knowledge, understanding and
      its application in design and conduct of the research protocol was collected
      using a dichotomous questionnaire. A descriptive statistics was used for data
      analysis. RESULTS: Nearly 79.2% students were aware of the importance of
      biostatistics in research, 55-65% were familiar with MS-EXCEL spreadsheet for
      graphical representation of data and with the statistical softwares available on
      the internet, 26.0% had biostatistics as mandatory subject in their curriculum,
      9.5% tried to perform statistical analysis on their own while 3.0% were
      successful in performing statistical analysis of their studies on their own.
      CONCLUSION: Biostatistics should play a central role in planning, conduct,
      interim analysis, final analysis and reporting of periodontal research especially
      by the postgraduate students. Indian postgraduate students in periodontics are
      aware of the importance of biostatistics in research but the level of
      understanding and application is still basic and needs to be addressed.

PMID- 24744548
TI  - Schizophrenia and periodontal disease: An oro-neural connection? A cross
      sectional epidemiological study.
AB  - BACKGROUND: Schizophrenia is a psychosis characterized by delusions and
      hallucinations occurring in clear consciousness. Studies have shown that the
      cytokines may modulate dopaminergic metabolism and schizophrenic symptomatology
      in schizophrenia. Cytokine involvement in periodontal disease is also well
      documented. To date, however, there has been relatively little research assessing
      periodontal status of patients with schizophrenia. The present study was
      therefore mainly intended to understand the exact link, if any, between
      periodontal disease and schizophrenia. MATERIALS AND METHODS: A total of 250
      schizophrenic patients (140 males and 110 females), between 25 and 55 years of
      age, were selected from the out patient department of National Institute of
      Mental Health and Neural Sciences, Bangalore and their periodontal status was
      assessed as part of this cross-sectional epidemiological survey. RESULTS: ANOVA
      showed that there was increased evidence of poor periodontal condition, as
      evidenced by gingival index and plaque index in patients who had been
      schizophrenic for a longer duration of time (P < 0.001). So also, higher probing
      pocket depths were found in schizophrenics suffering from a longer period of time
      than others (P < 0.001). CONCLUSIONS: Although oral neglect might be a cause of
      poor periodontal health in schizophrenics, the possible link between periodontal
      diseases giving rise to schizophrenia cannot be overlooked due to the presence of
      cytokine activity which is present both in schizophrenia and periodontal disease.

PMID- 24744549
TI  - Assessment of periodontal health status among prison inmates: A cross-sectional
      survey.
AB  - BACKGROUND: The prison population is a challenging one with many health problems,
      including oral health. In a country like India the information regarding the
      status of periodontal health in prisoners is scant. AIM: To assess the
      periodontal status of the jail inmates at Mangalore District Jail. MATERIALS AND
      METHODS: CROSS SECTIONAL SURVEY PARTICIPANTS: A Randomly selected sample of 82
      male inmates of age group 18-60 years were examined using community periodontal
      index (CPI) and loss of attachment from modified WHO oral health assessment
      proforma (1997). RESULTS: The prevalence of periodontal disease was 97.5%.
      Majority of the study population had CPI score of 2 and 1. Majority of the
      prisoners were severely affected with loss of attachment with 35% had loss of
      attachment more than 3 mm. CONCLUSION: As there are no oral health care
      facilities available in the prison set up, this study emphasizes the need for
      special attention from government and voluntary organizations to provide the oral
      health care services to inmates and improve the overall health status of the
      prisoners.

PMID- 24744550
TI  - Nigerian dentists' knowledge of aggressive periodontitis.
AB  - OBJECTIVE: To assess the general knowledge of Nigerian dentists on aggressive
      periodontitis (AgP) and specific knowledge of distinguishing between the clinical
      features of localized aggressive periodontitis (LAP) and generalized aggressive
      periodontitis (GAP). MATERIALS AND METHODS: A cross-sectional, non-random
      convenience survey was done on 200 dentists, in three geopolitical zones of
      Nigeria, using pre-tested, closed question- type questionnaires. Eventually, only
      133 questionnaires were analyzed. Relationships between six outcome variables
      namely clinical features of LAP, clinical features of GAP, LAP oral hygiene, GAP
      oral hygiene, laser therapy option and type of laser therapy, and the explanatory
      variables of gender and experience were analyzed. RESULTS: A total of 33.8% of
      the dentists had poor general knowledge, 16.5% had fair knowledge, 31.9% had good
      knowledge, while 10.5% had excellent knowledge. Gender- and experience-related
      differences were found, but they were not statistically significant. CONCLUSION:
      Both the general and specific knowledge of aggressive periodontitis among
      Nigerian dentists is less than expected and needs improvement through targeted,
      continuing dental education.

PMID- 24744551
TI  - Post-operative morbidity following the use of the inverted periosteal graft: A
      case series.
AB  - Post-operative complications following flap surgeries or mucogingival procedures
      are important factors influencing patient's perception of periodontal procedures.
      Hence, it is important to foresee such complications and take adequate measures
      pre- and post-operatively. We treated five consecutive cases of gingival
      recession in the maxillary canine-premolar area using the inverted periosteal
      graft with a coronally positioned flap technique. Following each of these
      surgeries, the patients complained of post-operative swelling the next day
      involving the canine space or buccal space area. The swelling persisted for at
      least 5 days, however, it was painless. This paper highlights the post-operative
      complications associated with the said procedure and makes a case for detail
      enquiry in the form of controlled studies. 

PMID- 24744552
TI  - Odontogenic fibroma WHO-type simulating periodontal disease: Report of a case.
AB  - Central odontogenic fibroma World Health Organization (WHO)-type (OFWT) is a rare
      lesion that has differential diagnosis with other radiolucent periapical lesions.
      It has a slow growth and is usually an asymptomatic lesion found in routine
      examinations. We report a case of a central OFWT occurring in the maxilla, for
      which the first symptom was teeth mobility, simulating a periodontal condition. A
      54-year-old woman, with superior premolar mobility, was referred to our clinic.
      An oral examination showed teeth vitality and advanced periodontal disease.
      Radiography showed a unilocular radiolucent area between the left superior
      lateral incisor and first left molar, with bone reabsorption. The granulomatous
      tissue was removed and microscopic examination revealed cellular connective
      tissue with multiple islands of odontogenic epithelium, covered by stratified
      squamous epithelium, confirming the OFWT diagnosis. The central OFWT is a non
      aggressive lesion, with rare recidivism. Biopsy is an important procedure for
      correct diagnosis and treatment, as some radiolucent lesions can lead to
      misdiagnosis. 

PMID- 24744553
TI  - Peripheral ossifying fibroma, some rare findings.
AB  - The peripheral ossifying fibroma (POF) is a benign reactive gingival overgrowth;
      it occurs mainly in the anterior portion of maxilla in young adults,
      predominantly among females. The present report describes a case of POF in a male
      patient, which relapsed ten years later and of the lesion showed superficial bone
      erosion on surgical excision. 

PMID- 24744554
TI  - Inflammatory hyperplasia: From diagnosis to treatment.
AB  - Gingival enlargement, the currently accepted terminology for an increase in the
      size of the gingiva, is a common feature of gingival disease. Local and systemic
      factors influence the gingival conditions of the patient. These factors results
      in a spectrum of diseases that can be developmental, reactive and inflammatory to
      neoplastic. In this article, the history, etiology, clinical and
      histopathological features, treatment strategies and preventive protocol of
      inflammatory hyperplasia are discussed. 

PMID- 24744555
TI  - An undiagnosed case of acute myeloid leukemia.
AB  - Leukemia is a neoplastic disease characterized by an excessive proliferation of
      immature white blood cells and their precursors. Oral lesions may be the
      presenting feature of acute leukemia, which can be rapidly fatal if left
      untreated. Although many cases of gingival enlargement in patients with acute
      myeloid leukemia's have been reported in the literature, cases diagnosed by the
      oral manifestations in India are very few. This report describes the case of a 43
      year-old female who presented with gingival bleeding and gingival enlargement.
      Within a month she developed signs and symptoms of systemic disease such as, and
      splenomegaly, and upon further investigation, she was diagnosed with acute
      myeloid leukemia to which she succumbed within 10 days after diagnosis. The need
      for early diagnosis and referral of this fatal disease are also underline. 

PMID- 24744556
TI  - Labial-cervical-vertical groove: A silent killer-Treatment of an intrabony defect
      due to it with platelet rich fibrin.
AB  - A 47-year-old male patient reported to the Department of Periodontology, with a
      chief complaint of pus discharge from maxillary left central incisors with dull
      intermittent pain. On clinical examination, a localized gingival inflammation was
      present with soft edematous tissue with the accumulation of plaque and calculus
      with #11 and #21. Periodontal examination depicts a periodontal pocket depth of
      11 mm on mesial aspect and 8 mm on midbuccal aspect of #21 with no mobility. On
      radiographic examination, a tear-shaped radiolucency was present with localized
      bone loss in #21. On careful examination, labial-cervical-vertical groove (LCVG)
      was found on #21 which was extending into gingival sulcus. This article reports
      the effectiveness of platelet rich fibrin for the treatment of intrabony defect
      associated with labial-cervical-vertical groove of #21. 

PMID- 24744557
TI  - Bilateral multiple recession coverage with platelet-rich fibrin in comparison
      with amniotic membrane.
AB  - Various plastic procedures are done to enhance esthetics, relieve
      hypersensitivity or even prevent root caries. The most predictable plastic
      procedure is the coronally advanced flap procedure, with subepithelial connective
      tissue. Owing to the second surgical donor site and difficulty in procuring a
      sufficient graft in multiple recessions, various alternative additive membranes
      are used. This is a case report, the first of its kind, wherein a bilaterally
      occurring multiple Millers class I recession was managed by using Platelet-rich
      Fibrin (PrF) and amniotic membrane, in a 40-year-old male, who presented to the
      Department of Periodontics. He complained of hypersensitivity in relation to the
      upper right and left back region, a bilateral Millers class I recession in
      relation to 15, 16, and 25, 26 of 3 mm each. Both the recessions were planned for
      root coverage with coronally advanced flap and additive membrane. The sites were
      randomly assigned for the use of platelet-rich fibrin and an aminotic membrane.
      The clinical outcome of the surgical procedure accounted for 100% root coverage,
      an enhanced gingival biotype, with both the membranes. Furthermore, the results
      were stable even after seven months in the amniotic membrane-treated site. Hence,
      the use of amniotic membrane as a novel approach to root coverage is more
      advantageous than PrF owing to the laboratory preparation of the autologous
      biomaterial. 

PMID- 24744558
TI  - Full mouth rehabilitation with zygomatic implants in patients with generalized
      aggressive periodontitis: 2 year follow-up of two cases.
AB  - Rehabilitation of severely atrophied maxillae is often a challenge and patients
      with generalized aggressive periodontitis (GAP) make it even more complicated.
      This clinical report describes rehabilitation of GAP patients with zygomatic
      implants and followed-up for 2 years. Two patients of age 33 and 44 reported to a
      private dental practice and were diagnosed with GAP. Various treatment options
      were considered after which it was decided to do a full mouth implant supported
      fixed rehabilitation, with a combination of conventional and zygomatic implants.
      Two zygomatic and four conventional implants were placed and immediately loaded
      with a provisional prosthesis. After 6 months, definitive prosthesis was
      delivered. Implants and prostheses were followed-up for 2 years. No implant
      failures occurred, but a few biological complications were observed. The most
      common clinical observation in these patients during recall visits was peri
      implant soft-tissue inflammation, which is a biological complication. This was
      with no trouble, controlled by using proper oral hygiene aids and maintenance.
      Within the limitations of this study, we can state that it can definitely be
      considered as a viable treatment option treating patients with GAP. However,
      studies with more follow-up time and controlled clinical trials should be
      performed in order to document the longevity of this treatment modality. 

PMID- 24744559
TI  - Haptics in periodontics.
AB  - Throughout history, education has evolved, and new teaching/learning methods have
      been developed. These methods have helped us come a long way in understanding the
      pathogenesis, diagnosis, and treatment of diseases of the oral cavity. However,
      there is still no one good way to render a student/clinician the tactile sense
      for detecting calculus/caries or placing the incisions or detecting the
      smoothness of a restoration or any treatment procedures before entering the
      clinics. In the education field, to improve the tactile sensation, the sense of
      touch and force-feedback can offer great improvements to the existing learning
      methods, thus enhancing the quality of education procedures. The concept of
      Haptics, which is extensively in use and indispensable in other fields like
      aviation, telecommunication etc., is now making its way into dentistry. Against
      this background, the following write-up intends to provide a glimpse of the
      coming wave of Haptics - A virtual reality system in dental education and
      discusses the strengths and weak points of this system. 

PMID- 24744560
TI  - The stem cell promise: The future of stemocytology.

PMID- 24744561
TI  - Fractures of the occipital condyle clinical spectrum and course in eight
      patients.
AB  - INTRODUCTION: Occipital condyle fractures (OCFs) are considered to be rare
      injuries. OCFs are now diagnosed more often because of the widespread use of
      computed tomography. Our aim is to report the incidence, treatment and long term
      outcome of 8 patients with OCFs. MATERIALS AND METHODS: All patients presenting
      with multiple trauma from 1993 to 2006 were analyzed retrospectively.
      Characteristics and course of the treatment were evaluated. Follow-up was
      performed after 11,7 years (range 5,9 to 19,3 years). RESULTS: Nine cases of OCF
      in 8 patients were identified. All injuries resulted from high velocity trauma.
      The average scores on the ISS Scale were 39,6 (24-75) and 7,3 (3-15) on the GCS.
      According to Anderson's classification, 5 cases of Type III and 4 cases of Type I
      fractures were identified. According to Tuli's classification, 5 cases of Type
      IIA and 4 cases of Type I were found. Indications for immobilization with the
      halo-vest were type III injuries according to Anderson's classification or Tuli's
      type IIA injuries, respectively. Patients with Tuli's type I injuries were
      treated with a Philadelphia collar for 6 weeks. In one patient with initial
      complete tetraplegia and one with incomplete neurological deficits the final
      follow-up neurologic examination showed no neurological impairment at all
      (Frankel-grade A to E, respectively B to E). At follow-up, 3 patients were
      asymptomatic. Four patients suffered from mild pain when turning their head, pain
      medication was necessary in one case only. DISCUSSION: OCF's are virtually
      undetectable using conventional radiography. In cases of high velocity, cranio
      cervical trauma or impaired consciousness, high resolution CT-scans of the
      craniocervical junction must be performed. We suggest immobilization using a halo
      device for type III injuries according to Anderson's classification or Tuli's
      type IIa injuries, respectively. Patients with Tuli's type I injuries should be
      treated with a Philadelphia collar.

PMID- 24744562
TI  - Alternative technique of cervical spinal stabilization employing lateral mass
      plate and screw and intra-articular spacer fixation.
AB  - AIM: The author discusses an alternative technique of segmental cervical spinal
      fixation. MATERIAL AND METHODS: The subtleties of the technique are discussed on
      the basis of experience with 3 cases with a follow-up of between 30 and 36
      months. TECHNIQUE: The technique involves debridement of facetal articular
      cartilage, distraction of facets, jamming of 'Goel spacer' into the articular
      cavity and fortification of the fixation by lateral mass plate and screw
      fixation. The 'double-insurance' method of fixation is safe for vertebral artery,
      nerve roots and spinal neural structures and the fixation is strong. CONCLUSIONS:
      The discussed technique is safe and provides a strong fixation and a ground for
      ultimate arthrodesis.

PMID- 24744563
TI  - A new technique in the surgical treatment of Hangman's fractures: Neurospinal
      Academy (NSA) technique.
AB  - CONTEXT: Treatment of Hangman's fractures is still controversial. Hangman's
      fractures Type II and IIA are usually treated with surgical procedures. AIM: This
      study aims at describing the Neurospinal Academy (NSA) technique as an attempt to
      achieve an approximation of the fracture line to the axis body, which may be used
      for Type II and IIA patients with severe displacement and angulation. SETTINGS
      AND DESIGN: NSA technique both pars or pedicle screws are placed bicortically to
      ensure that anterior surface of C2 vertebral body will be crossed 1-2 mm. A rod
      is prepared in suitable length and curve to connect the two screws. For placing
      the rod, sufficient amount of bone is resected from the C2 spinous process. C2
      vertebral body is pulled back by means of the screws that crossed the anterior
      surface of C2 vertebral body. MATERIALS AND METHODS: Hangman II and IIA patient
      are treated with NSA technique. RESULT: Angulated and tilted C2 vertebral body
      was pulled back and approximated to posterior elements. CONCLUSIONS: In Hangman's
      fractures Type II and IIA with severe vertebral body and pedicle displacement,
      NSA technique is an effective and reliable treatment alternative for the
      approximation of posterior elements to the C2 vertebral body, which is tilted,
      angulated, and dislocated.

PMID- 24744564
TI  - Only fixation for cervical spondylosis: Report of early results with a
      preliminary experience with 6 cases.
AB  - AIM: The author reports early post-operative outcome and preliminary experience
      with an alternative form of treatment of cervical degenerative or spondylotic
      disease leading to spinal canal stenosis that involves fixation-arthrodesis of
      the affected spinal segment using one or two (double insurance) transarticular
      screws for each joint. MATERIALS AND METHODS: During the period of months from
      March 2013 to July 2013, six patients having cervical spondylotic cord
      compression were treated with transarticular method of screw fixation of the
      involved segments. The operation involved section of the spinous process at its
      base, opening up of the facet joint, denuding of articular cartilage, placement
      of intraarticular cavity bone graft chips and insertion of either a single or two
      transarticular screws at each level. The fixation was done in four levels in four
      patients and at two levels in two patients. Japanese Orthopedic Association
      score, visual analog scale (neck pain) and Odom's criteria were used to monitor
      the clinical status of the patients before and after the surgery and at follow
      up. RESULTS: Immediate post-operative and a relatively short-term post-operative
      outcome was remarkably gratifying. During the average period of follow-up of 6
      months (range: 3-8 months); there was varying degree of recovery of symptoms. The
      procedure resulted in firm stabilization and fixation of the spinal segment and
      provided a ground for arthrodesis. No patient worsened after treatment. During
      the period of follow-up, all patients showed remarkable and progressive recovery
      in symptoms. CONCLUSIONS: Vertical instability and telescoping, listhesis or
      overriding of the facets on physical activity seems to be the defining phenomenon
      in pathogenesis of cervical spondylotic disease. The clinical outcome in our
      patients suggest that only fixation of the spinal segment can be a rationale form
      of treatment. Transarticular method of treatment is a simple, safe and effective
      method of spinal stabilization. The firm stabilization at the fulcrum of cervical
      spinal movements provided a ground for segmental spinal arthrodesis. Use of two
      or "double insurance" screws at each facet is possible and provides reassuring
      stability in selected cases.

PMID- 24744565
TI  - Aggressive osteoblastoma involving the craniovertebral junction: A case report
      and review of literature.
AB  - Osteoblastoma (OB) is a rare bony neoplasm constituting around 1% of all primary
      bone tumors. Although the vertebrae and long bones are the most common sites
      affected by OB, skull remains a relatively uncommon site of occurrence.
      Aggressive variant of OB is histologically intermediate between an indolent
      conventional OB and a malignant osteosarcoma. To the best of our knowledge,
      aggressive osteoblastoma (AO) affecting the craniovertebral junction has not been
      previously described in the literature. In this report, we present a 34-year-old
      gentleman who presented with a mass involving the left side of the neck and oral
      cavity along with ipsilateral lower cranial nerve paresis. Computed tomography
      and magnetic resonance imaging scans of the craniovertebral junction revealed a
      heterogeneously enhancing expansile lesion with areas of destruction involving
      the clivus, left sided jugular foramen and left side of first two cervical
      vertebras. Angiography showed distortion of the V3 segment of the left vertebral
      artery and shift of the ipsilateral internal carotid artery. The tumor was
      maximally excised through far lateral approach. Histopathologic examination
      revealed a diagnosis of AO. The patient was referred for radiotherapy for the
      residual tumor and was doing well at 5 months follow-up. 

PMID- 24744566
TI  - Unilateral lateral mass hypertrophy: An extremely rare congenital anomaly of
      atlas.
AB  - A wide variety of congenital anomalies are observed around the craniovertebral
      junctional area. However, hypertrophied unilateral lateral mass of atlas in
      association with chiari-1 malformation leading to myelopathy is extremely
      uncommon. Herein we report a case of 28-year-old female who presented to us with
      a high cervical compressive myelopathy. Imaging revealed bony hypertrophy
      involving right sided C1 lateral mass along with chiari malformation-type 1. She
      underwent transoral as well as posterior decompression followed by occipito
      cervical fusion. The authors discuss their case in light of other such reported
      cases and present a review of the literature. 

PMID- 24744568
TI  - A rare case of spontaneous Aspergillus spondylodiscitis with epidural abscess in
      a 45-year-old immunocompetent female.
AB  - Vertebral osteomyelitis and discitis are mainly due to bacterial infections
      though fungal infections are one of the important causes of morbidity and
      mortality in immunocompromised patients. Aspergillus involving intervertebral
      disc space is extremely rare. We report a case of aspergillosis of intervertebral
      L5-S1 disc space with spinal epidural abscess in an immunocompetent 45-year-old
      female which can add on to a few case reports described in literature as well as
      an insight for clinicians regarding this rare spontaneous infection in an
      immunocompetent patient. 

PMID- 24744567
TI  - Isolated spinal neurosarcoidosis: An enigmatic intramedullary spinal cord
      pathology-case report and review of the literature.
AB  - Isolated spinal cord neurosarcoidosis (NS) in the absence of systemic disease or
      intracranial involvement is exceptionally rare. Adjunctive laboratory tests
      though useful may not be reliable and the absence of any pathognomonic
      radiological features makes the diagnosis difficult. As spinal cord NS may be a
      presenting feature of systemic sarcoidosis which may be occult on routine workup,
      (18)F-fluorodeoxyglucose-positron emission tomography (FDG-PET) may be of value
      in unraveling this systemic involvement avoiding biopsying the spinal cord. A
      case of truly isolated NS is described with review of literature on this
      enigmatic pathology. Long segment intramedullary signal changes with focal
      parenchymal along with dural/meningeal enhancement in the absence of significant
      cervical stenosis in a young patient of northern European or African-American
      decent is very suggestive of NS and although may be presumably treated with
      steroids; there should be a low threshold for spinal cord biopsy especially in
      the absence of response to steroids to confirm isolated spinal cord NS in a
      patient with clinical neurological deterioration. 

PMID- 24744569
TI  - Unique paradoxical atlantoaxial dislocation with C1-C2 facet diastases and
      isolated ligamentous injury to the craniovertebral junction without neurological
      deficits: A case report.
AB  - STUDY DESIGN: Retrospective review of the case file. OBJECTIVE: The primary
      objective was to report this rare case and discuss the mechanism of dislocation
      and technique of manual closed reduction of C1-C2 vertebrae in such scenarios.
      SUMMARY OF BACKGROUND DATA: Posterior atlantoaxial dislocation (AAD) is extremely
      rare and a few cases have been reported in English literature. This young man
      sustained a high speed car accident and survived an extreme hyperextension injury
      to the craniovertebral junction (CVJ) without any neurological deficits. On
      evaluation for neck pain he was noted with a dislocated odontoid lying in front
      of Atlas. There was C1-C2 facet diastases. No bony injury was noted at CVJ.
      Transverse axial ligament (TAL) was intact. He underwent a successful awake
      reduction of the dislocation. The joint had to be manually distracted, realigned,
      and released under the guidance of fluoroscopy. This was followed by single stage
      C1-C2 Goel's fusion with awake prone positioning. This patient was able to go
      back to work at the end of 3 months (GOS 5). CONCLUSIONS: This condition is
      extremely rare, can be carefully reduced manually under adequate neuromonitoring,
      and requires C1-C2 fusion in the same sitting.

PMID- 24744570
TI  - Natural history of hepatic metastases from colorectal cancer--pathobiological
      pathways with clinical significance.
AB  - Colorectal cancer hepatic metastases represent the final stage of a multi-step
      biological process. This process starts with a series of mutations in colonic
      epithelial cells, continues with their detachment from the large intestine,
      dissemination through the blood and/or lymphatic circulation, attachment to the
      hepatic sinusoids and interactions with the sinusoidal cells, such as sinusoidal
      endothelial cells, Kupffer cells, stellate cells and pit cells. The metastatic
      sequence terminates with colorectal cancer cell invasion, adaptation and
      colonisation of the hepatic parenchyma. All these events, termed the colorectal
      cancer invasion-metastasis cascade, include multiple molecular pathways,
      intercellular interactions and expression of a plethora of chemokines and growth
      factors, and adhesion molecules, such as the selectins, the integrins or the
      cadherins, as well as enzymes including matrix metalloproteinases. This review
      aims to present recent advances that provide insights into these cell-biological
      events and emphasizes those that may be amenable to therapeutic targeting. 

PMID- 24744571
TI  - Gastro-intestinal toxicity of chemotherapeutics in colorectal cancer: the role of
      inflammation.
AB  - Chemotherapy-induced diarrhea (CID) is a common and often severe side effect
      experienced by colorectal cancer (CRC) patients during their treatment. As
      chemotherapy regimens evolve to include more efficacious agents, CID is
      increasingly becoming a major cause of dose limiting toxicity and merits further
      investigation. Inflammation is a key factor behind gastrointestinal (GI) toxicity
      of chemotherapy. Different chemotherapeutic agents activate a diverse range of
      pro-inflammatory pathways culminating in distinct histopathological changes in
      the small intestine and colonic mucosa. Here we review the current understanding
      of the mechanisms behind GI toxicity and the mucositis associated with systemic
      treatment of CRC. Insights into the inflammatory response activated during this
      process gained from various models of GI toxicity are discussed. The inflammatory
      processes contributing to the GI toxicity of chemotherapeutic agents are
      increasingly being recognised as having an important role in the development of
      anti-tumor immunity, thus conferring added benefit against tumor recurrence and
      improving patient survival. We review the basic mechanisms involved in the
      promotion of immunogenic cell death and its relevance in the treatment of
      colorectal cancer. Finally, the impact of CID on patient outcomes and therapeutic
      strategies to prevent or minimise the effect of GI toxicity and mucositis are
      discussed. 

PMID- 24744572
TI  - Inhibition of host immune response in colorectal cancer: human leukocyte antigen
      G and beyond.
AB  - Colorectal cancer (CRC) is one of the most diffuse cancers worldwide and is still
      a clinical burden. Increasing evidences associate CRC clinical outcome to immune
      contexture represented by adaptive immune cells. Their type, density and location
      are summarized in the Immune Score that has been shown to improve prognostic
      prediction of CRC patients. The non-classical MHC class I human leukocyte antigen
      G (HLA-G), is a crucial tumor-driven immune escape molecule involved in immune
      tolerance. HLA-G and soluble counterparts are able to exert inhibitory functions
      by direct interactions with inhibitory receptors present on both innate cells
      such as natural killer cells, and adaptive immune cells as cytotoxic T and B
      lymphocytes. HLA-G may play a prominent role in CRC strategies to avoid host
      immunosurveillance. This review highlights the current knowledge on HLA-G
      contribution in CRC, in related inflammatory diseases and in other type of
      cancers and disorders. HLA-G genetic setting (specific haplotypes, genotypes and
      alleles frequencies) and association with circulating/soluble profiles was
      highlighted. HLA G prognostic and predictive value in CRC was investigated in
      order to define a novel prognostic immune biomarker in CRC. 

PMID- 24744573
TI  - Role of preoperative CT colonography in patients with colorectal cancer.
AB  - In patients with colorectal cancer (CRC), accurate preoperative evaluation is
      essential for a correct therapeutic plan. Colonoscopy and intravenous contrast
      enhanced computed tomography (CT) are currently recommended in the preoperative
      work-up for CRC. Preoperative colonoscopy has some limitations such as
      misdiagnosis of synchronous cancers in cases of incomplete exploration of the
      colon and inaccurate tumor localization. Intravenous contrast-enhanced CT
      successfully documents distant metastases although it sometimes enables
      unsatisfactory locoregional staging. Computed tomography colonography (CTC) is
      obtained after gas insufflation of the colon and offers a comprehensive
      preoperative evaluation in patients with CRC, including a definition of the
      segmental location of the tumor, presence of synchronous lesions or lack thereof,
      and fairly accurate locoregional staging. CTC has some limitations, including a
      lack of biopsy capability, suboptimal sensitivity for synchronous small polyps,
      and unsatisfactory nodal staging. Bearing in mind these limitations, CTC could be
      employed as a "one-stop-shop" examination for preoperative assessment in patients
      with CRC. 

PMID- 24744574
TI  - Proteomics for discovery of candidate colorectal cancer biomarkers.
AB  - Colorectal cancer (CRC) is the second most common cause of cancer-related deaths
      in Europe and other Western countries, mainly due to the lack of well-validated
      clinically useful biomarkers with enough sensitivity and specificity to detect
      this disease at early stages. Although it is well known that the pathogenesis of
      CRC is a progressive accumulation of mutations in multiple genes, much less is
      known at the proteome level. Therefore, in the last years many proteomic studies
      have been conducted to find new candidate protein biomarkers for diagnosis,
      prognosis and as therapeutic targets for this malignancy, as well as to elucidate
      the molecular mechanisms of colorectal carcinogenesis. An important advantage of
      the proteomic approaches is the capacity to look for multiple differentially
      expressed proteins in a single study. This review provides an overview of the
      recent reports describing the different proteomic tools used for the discovery of
      new protein markers for CRC such as two-dimensional electrophoresis methods,
      quantitative mass spectrometry-based techniques or protein microarrays.
      Additionally, we will also focus on the diverse biological samples used for CRC
      biomarker discovery such as tissue, serum and faeces, besides cell lines and
      murine models, discussing their advantages and disadvantages, and summarize the
      most frequently identified candidate CRC markers. 

PMID- 24744575
TI  - Colorectal cancer screening: 20 years of development and recent progress.
AB  - Colorectal cancer (CRC) is the second most common cancer in Europe and its
      incidence is steadily increasing. This trend could be reversed through timely
      secondary prevention (screening). In the last twenty years, CRC screening
      programs across Europe have experienced considerable improvements (fecal occult
      blood testing; transition from opportunistic to population based program
      settings). The Czech Republic is a typical example of a country with a long
      history of nationwide CRC screening programs in the face of very high CRC
      incidence and mortality rates. Each year, approximately 8000 people are diagnosed
      with CRC and some 4000 die from this malignancy. Twenty years ago, the first
      pilot studies on CRC screening led to the introduction of the opportunistic Czech
      National Colorectal Cancer Screening Program in 2000. Originally, this program
      was based on the guaiac fecal occult blood test (FOBT) offered by general
      practitioners, followed by colonoscopy in cases of FOBT positivity. The program
      has continuously evolved, namely with the implementation of immunochemical FOBTs
      and screening colonoscopy, as well as the involvement of gynecologists. Since the
      establishment of the Czech CRC Screening Registry in 2006, 2405850 FOBTs have
      been performed and 104565 preventive colonoscopies recorded within the screening
      program. The overall program expanded to cover 25.0% of the target population by
      2011. However, stagnation in the annual number of performed FOBTs lately has led
      to switching to the option of a population-based program with personal
      invitation, which is currently being prepared. 

PMID- 24744576
TI  - Chemopreventive drugs: mechanisms via inhibition of cancer stem cells in
      colorectal cancer.
AB  - Recent epidemiological studies, basic research and clinical trials on colorectal
      cancer (CRC) prevention have helped identify candidates for effective
      chemopreventive drugs. However, because of the conflicting results of clinical
      trials or side effects, the effective use of chemopreventive drugs has not been
      generalized, except for patients with a high-risk for developing hereditary CRC.
      Advances in genetic and molecular technologies have highlighted the greater
      complexity of carcinogenesis, especially the heterogeneity of tumors. We need to
      target cells and processes that are critical to carcinogenesis for
      chemoprevention and treatment of advanced cancer. Recent research has shown that
      intestinal stem cells may serve an important role in tumor initiation and
      formation of cancer stem cells. Moreover, studies have shown that the tumor
      microenvironment may play additional roles in dedifferentiation, to enable tumor
      cells to take on stem cell features and promote the formation of tumorigenic stem
      cells. Therefore, early tumorigenic changes of stem cells and signals for
      dedifferentiation may be good targets for chemoprevention. In this review, I
      focus on cancer stem cells in colorectal carcinogenesis and the effect of major
      chemopreventive drugs on stem cell-related pathways. 

PMID- 24744577
TI  - Current and future molecular diagnostics in colorectal cancer and colorectal
      adenoma.
AB  - Colorectal cancer (CRC) is one of the most prevalent cancers in developed
      countries. On the other hand, CRC is also one of the most curable cancers if it
      is detected in early stages through regular colonoscopy or sigmoidoscopy. Since
      CRC develops slowly from precancerous lesions, early detection can reduce both
      the incidence and mortality of the disease. Fecal occult blood test is a widely
      used non-invasive screening tool for CRC. Although fecal occult blood test is
      simple and cost-effective in screening CRC, there is room for improvement in
      terms of the accuracy of the test. Genetic dysregulations have been found to play
      an important role in CRC development. With better understanding of the molecular
      basis of CRC, there is a growing expectation on the development of diagnostic
      tests based on more sensitive and specific molecular markers and those tests may
      provide a breakthrough to the limitations of current screening tests for CRC. In
      this review, the molecular basis of CRC development, the characteristics and
      applications of different non-invasive molecular biomarkers, as well as the
      technologies available for the detection were discussed. This review intended to
      provide a summary on the current and future molecular diagnostics in CRC and its
      pre-malignant state, colorectal adenoma. 

PMID- 24744578
TI  - Predictive and prognostic biomarkers with therapeutic targets in advanced
      colorectal cancer.
AB  - Colorectal cancer (CRC) is one of the most common human malignant diseases and
      the second leading cause of cancer-related deaths worldwide. The treatment of
      advanced CRC has improved significantly in recent years. With the emergence of
      two targeted antibodies, cetuximab (Erbitux), an anti-epidermal growth factor
      receptor monoclonal antibody and bevacizumab (Avastin), a vascular endothelial
      growth factor monoclonal antibody, the treatment of metastatic CRC has entered
      the era of personalized therapy. Predictive and prognostic biomarkers have, and
      will continue to, facilitate the selection of suitable patients and the
      personalization of treatment for metastatic CRC (mCRC). In this review, we will
      focus primarily on the important progresses made in the personalized treatment of
      mCRC and discuss the potentially novel predictive and prognostic biomarkers for
      improved selection of patients for anti-cancer treatment in the future. 

PMID- 24744579
TI  - Extent of lymphadenectomy and perioperative therapies: two open issues in gastric
      cancer.
AB  - Gastric cancer is one of the leading causes of death for cancer worldwide,
      although geographical variations in incidence exist. Over the last decades, its
      incidence and mortality have gradually decreased in Western countries, while
      these have increased, or remained stable, in the other world regions. Gastric
      cancer is often diagnosed at an advanced stage, with the only notable exception
      of Japan, where nationwide screening programs are enforced, due to local high
      incidence. Curative- intent surgery (i.e., gastrectomy, total or partial, and
      lymphadenectomy) remains the cornerstone of treatment of gastric cancer. Much has
      been debated about the extent of lymph node dissection and, although it is a
      valuable contribution to staging and cure, operative treatment only represents
      one aspect of overall effective management, as the risk of both locoregional and
      distant recurrences are high, and bear a poor prognosis. As a matter of fact,
      surgery, as a single modality treatment, has probably achieved its maximum
      efficacy for local control and survival, while other accompanying nonsurgical
      treatment modalities have to be taken into account, although their role is still
      the subject of considerable debate. The authors in this review present an update
      on the outcome of treatment of gastric cancer in relation to the extent of
      lymphadenectomy and of various nonsurgical preoperative, intraoperative, and
      postoperative strategies. 

PMID- 24744580
TI  - Treatment options in patients with metastatic gastric cancer: current status and
      future perspectives.
AB  - Despite advances in the treatment of gastric cancer, it remains the world's
      second highest cause of cancer death. As gastric cancer is often diagnosed at an
      advanced stage, systemic chemotherapy is the mainstay of treatment for these
      patients. However, no standard palliative chemotherapy regimen has been accepted
      for patients with metastatic gastric cancer. Palliative chemotherapy including
      fluoropyrimidine, platin compounds, docetaxel and epirubicin prolongs survival,
      and improves a high quality of life to a greater extent than best supportive
      care. The number of clinical investigations associated with targeted agents has
      recently increased. Agents targeting the epidermal growth factor receptor 1 and
      human epidermal growth factor receptor 2 (HER2) have been widely tested.
      Trastuzumab was the first target drug developed, and pivotal phase III trials
      showed improved survival when trastuzumab was integrated into
      cisplatin/fluoropyrimidine-based chemotherapy in patients with metastatic gastric
      cancer. Trastuzumab in combination with chemotherapy was thus approved to be a
      new standard of care for patients with HER2-positive advanced esophagogastric
      adenocarcinoma. Thus, the evaluation of HER2 status in all patients with
      metastatic gastroesophageal adenocarcinoma should be considered. Other agents
      targeting vascular endothelial growth factor, mammalian target of rapamycin, and
      other biological pathways have also been investigated in clinical trials, but
      showed little impact on the survival of patients. In this review, systemic
      chemotherapy and targeted therapies for metastatic gastric cancer in the first-
      and second-line setting are summarized in the light of recent advances. 

PMID- 24744581
TI  - DNA methylation in gastric cancer, related to Helicobacter pylori and Epstein
      Barr virus.
AB  - Gastric cancer is a leading cause of cancer death worldwide, and significant
      effort has been focused on clarifying the pathology of gastric cancer. In
      particular, the development of genome-wide analysis tools has enabled the
      detection of genetic and epigenetic alterations in gastric cancer; for example,
      aberrant DNA methylation in gene promoter regions is thought to play a crucial
      role in gastric carcinogenesis. The etiological viewpoint is also essential for
      the study of gastric cancers, and two distinct pathogens, Helicobacter pylori (H.
      pylori) and Epstein-Barr virus (EBV), are known to participate in gastric
      carcinogenesis. Chronic inflammation of the gastric epithelium due to H. pylori
      infection induces aberrant polyclonal methylation that may lead to an increased
      risk of gastric cancer. In addition, EBV infection is known to cause extensive
      methylation, and EBV-positive gastric cancers display a high methylation
      epigenotype, in which aberrant methylation extends to not only Polycomb
      repressive complex (PRC)-target genes in embryonic stem cells but also non-PRC
      target genes. Here, we review aberrant DNA methylation in gastric cancer and the
      association between methylation and infection with H. pylori and EBV. 

PMID- 24744582
TI  - An updated review of gastric cancer in the next-generation sequencing era:
      insights from bench to bedside and vice versa.
AB  - Gastric cancer (GC) is one of the most common malignancies and remains the second
      leading cause of cancer-related death worldwide. There is an increasing
      understanding of the roles that genetic and epigenetic alterations play in GCs.
      Recent studies using next-generation sequencing (NGS) have revealed a number of
      potential cancer-driving genes in GC. Whole-exome sequencing of GC has identified
      recurrent somatic mutations in the chromatin remodeling gene ARID1A and
      alterations in the cell adhesion gene FAT4, a member of the cadherin gene family.
      Mutations in chromatin remodeling genes (ARID1A, MLL3 and MLL) have been found in
      47% of GCs. Whole-genome sequencing and whole-transcriptome sequencing analyses
      have also discovered novel alterations in GC. Recent studies of cancer
      epigenetics have revealed widespread alterations in genes involved in the
      epigenetic machinery, such as DNA methylation, histone modifications, nucleosome
      positioning, noncoding RNAs and microRNAs. Recent advances in molecular research
      on GC have resulted in the introduction of new diagnostic and therapeutic
      strategies into clinical settings. The anti-human epidermal growth receptor 2
      (HER2) antibody trastuzumab has led to an era of personalized therapy in GC. In
      addition, ramucirumab, a monoclonal antibody targeting vascular endothelial
      growth factor receptor (VEGFR)-2, is the first biological treatment that showed
      survival benefits as a single-agent therapy in patients with advanced GC who
      progressed after first-line chemotherapy. Using NGS to systematically identify
      gene alterations in GC is a promising approach with remarkable potential for
      investigating the pathogenesis of GC and identifying novel therapeutic targets,
      as well as useful biomarkers. In this review, we will summarize the recent
      advances in the understanding of the molecular pathogenesis of GC, focusing on
      the potential use of these genetic and epigenetic alterations as diagnostic
      biomarkers and novel therapeutic targets. 

PMID- 24744583
TI  - Endoscopic submucosal dissection for undifferentiated-type early gastric cancer:
      do we have enough data to support this?
AB  - Although endoscopic submucosal dissection (ESD) is now accepted for treatment of
      early gastric cancers (EGC) with negligible risk of lymph node (LN) metastasis,
      ESD for intramucosal undifferentiated type EGC without ulceration and with
      diameter <= 2 cm is regarded as an investigational treatment according to the
      Japanese gastric cancer treatment guidelines. This consideration was largely
      based on the analysis of surgically resected EGCs that contained undifferentiated
      type EGCs; however, results from several institutes showed some discrepancies in
      sample size and incidence of LN metastasis. Recently, some reports about the
      safety and efficacy of ESD for undifferentiated type EGC meeting the expanded
      criteria have been published. Nonetheless, only limited data are available
      regarding long-term outcomes of ESD for EGC with undifferentiated histology so
      far. At the same time, endoscopists cannot ignore the patients' desire to
      guarantee quality of life after the relatively non-invasive endoscopic treatment
      when compared to conventional surgery. To satisfy the needs of patients and
      provide solid evidence to support ESD for undifferentiated EGC, we need more
      delicate tools to predict undetected LN metastasis and more data that can reveal
      predictive factors for LN metastasis. 

PMID- 24744584
TI  - Somatic alterations in mitochondrial DNA and mitochondrial dysfunction in gastric
      cancer progression.
AB  - Energy metabolism reprogramming was recently identified as one of the cancer
      hallmarks. One of the underlying mechanisms of energy metabolism reprogramming is
      mitochondrial dysfunction caused by mutations in nuclear genes or mitochondrial
      DNA (mtDNA). In the past decades, several types of somatic mtDNA alterations have
      been identified in gastric cancer. However, the role of these mtDNA alterations
      in gastric cancer progression remains unclear. In this review, we summarize
      recently identified somatic mtDNA alterations in gastric cancers as well as the
      relationship between these alterations and the clinicopathological features of
      gastric cancer. The causative factors and potential roles of the somatic mtDNA
      alterations in cancer progression are also discussed. We suggest that point
      mutations and mtDNA copy number decreases are the two most common mtDNA
      alterations that result in mitochondrial dysfunction in gastric cancers. The two
      primary mutation types (transition mutations and mononucleotide or dinucleotide
      repeat instability) imply potential causative factors. Mitochondrial dysfunction
      generated reactive oxygen species may be involved in the malignant changes of
      gastric cancer. The search for strategies to prevent mtDNA alterations and
      inhibit the mitochondrial retrograde signaling will benefit the development of
      novel treatments for gastric cancer and other malignancies. 

PMID- 24744585
TI  - New insights into the functions and localization of the homeotic gene CDX2 in
      gastric cancer.
AB  - Gastric cancer is one of the most frequent cancers, and it ranks the third most
      common cancer in China. The most recently caudal-related homeobox transcription
      factor 2 (CDX2) is expressed in a large number of human gastrointestinal cancers.
      In addition, gastric epithelial cell mutations in CDX2 result in tumor promotion,
      which is characterized by cellular drug resistance and a high proclivity for
      developing cancer. A series of publications over the past years suggests a
      mechanism by which CDX2 overexpression results in multidrug resistance. CDX2
      appears to forward control regenerating IV and the multidrug resistance 1
      expression signaling pathway for regulation of cell drug resistance. 

PMID- 24744586
TI  - Clinical significance of lymph node metastasis in gastric cancer.
AB  - Gastric cancer, one of the most common malignancies in the world, frequently
      reveals lymph node, peritoneum, and liver metastases. Most of gastric cancer
      patients present with lymph node metastasis when they were initially diagnosed or
      underwent surgical resection, which results in poor prognosis. Both the depth of
      tumor invasion and lymph node involvement are considered as the most important
      prognostic predictors of gastric cancer. Although extended lymphadenectomy was
      not considered a survival benefit procedure and was reported to be associated
      with high mortality and morbidity in two randomized controlled European trials,
      it showed significant superiority in terms of lower locoregional recurrence and
      disease related deaths compared to limited lymphadenectomy in a 15-year follow-up
      study. Almost all clinical investigators have reached a consensus that the
      predictive efficiency of the number of metastatic lymph nodes is far better than
      the extent of lymph node metastasis for the prognosis of gastric cancer
      worldwide, but other nodal metastatic classifications of gastric cancer have been
      proposed as alternatives to the number of metastatic lymph nodes for improving
      the predictive efficiency for patient prognosis. It is still controversial over
      whether the ratio between metastatic and examined lymph nodes is superior to the
      number of metastatic lymph nodes in prognostic evaluation of gastric cancer.
      Besides, the negative lymph node count has been increasingly recognized to be an
      important factor significantly associated with prognosis of gastric cancer. 

PMID- 24744587
TI  - Post-infectious irritable bowel syndrome: mechanistic insights into chronic
      disturbances following enteric infection.
AB  - Irritable bowel syndrome (IBS) is a commonly encountered chronic functional
      gastrointestinal (GI) disorder. Approximately 10% of IBS patients can trace the
      onset of their symptoms to a previous a bout of infectious dysentery. The
      appearance of new IBS symptoms following an infectious event is defined as post
      infectious-IBS. Indeed, with the World Health Organization estimating between 2
      and 4 billion cases annually, infectious diarrheal disease represents an
      incredible international healthcare burden. Additionally, compounding evidence
      suggests many commonly encountered enteropathogens as unique triggers behind IBS
      symptom generation and underlying pathophysiological features. A growing body of
      work provides evidence supporting a role for pathogen-mediated modifications in
      the resident intestinal microbiota, epithelial barrier integrity, effector cell
      functions, and innate and adaptive immune features, all proposed physiological
      manifestations that can underlie GI abnormalities in IBS. Enteric pathogens must
      employ a vast array of machinery to evade host protective immune mechanisms, and
      illicit successful infections. Consequently, the impact of infectious events on
      host physiology can be multidimensional in terms of anatomical location,
      functional scope, and duration. This review offers a unique discussion of the
      mechanisms employed by many commonly encountered enteric pathogens that cause
      acute disease, but may also lead to the establishment of chronic GI dysfunction
      compatible with IBS. 

PMID- 24744589
TI  - Epithelial membrane protein 1 negatively regulates cell growth and metastasis in
      colorectal carcinoma.
AB  - AIM: To determine the expression and function of epithelial membrane protein 1
      (EMP1) in colorectal carcinoma. METHODS: Colorectal samples were taken from
      cancer lesions and adjacent normal tissue in colorectal cancer patients
      immediately after endoscopic biopsy. A portion of the sample was either fixed in
      4% paraformaldehyde and embedded in paraffin for immunohistochemistry or stored
      in liquid nitrogen for Western blot. In order to determine protein expression of
      EMP1 in colorectal cancer (n = 63) and normal tissue (n = 31), semi-quantitative
      immunohistochemistry and Western blot were utilized. For in vitro studies, the
      human colorectal cancer cell line SW-480 was maintained in RPMI-1640 medium
      supplemented with 10% fetal bovine serum. Recombinant lentivirus mediated
      overexpression of EMP1 in SW-480 cells was quantified by real-time reverse
      transcription-polymerase chain reaction and Western blot. Control SW-480 cells
      were transfected with an empty vector. To further study the effect of EMP1
      overexpression in SW-480 cells, cell proliferation, apoptosis, migration and
      invasion assays were conducted. RESULTS: Expression of EMP1 was significantly
      lower in colorectal cancer tissue than in normal tissue using both
      immunohistochemistry (39.7% vs 90.3% of tissues, P < 0.05) and Western blot
      (0.126 +/- 0.022 vs 0.632 +/- 0.053, P < 0.05). The level of EMP1 protein
      expression was not correlated with gender, age, or tumor location. Decreased
      expression of EMP1 was significantly correlated with T stage, lymph node
      metastasis, clinic stage, and histological grade in patients with colorectal
      cancer (P < 0.05). According to Kaplan-Meier analysis, low EMP1 expression
      correlated significantly with poor overall five-year survival (34.2% vs 64.0%
      survival, P < 0.05). SW-480 cells transfected with EMP1 had a lower survival
      fraction, higher cell apoptosis (12.1% +/- 1.3% vs 3.1% +/- 0.6%, P < 0.05), a
      significant decrease in migration and invasion (124.0 +/- 17.0 and 87.0 +/- 12.0,
      respectively vs 213.0 +/- 29.0 and 178.0 +/- 21.0, respectively, P < 0.05),
      higher caspase-9 (0.635 +/- 0.063 vs 0.315 +/- 0.032, P < 0.05), and lower VEGFC
      protein expression (0.229 +/- 0.021 vs 0.519 +/- 0.055, P < 0.05) relative to
      cells not transfected with EMP1. CONCLUSION: Low EMP1 expression in colorectal
      cancer is associated with increased disease severity, suggesting that EMP1 may be
      a negative regulator of colorectal cancer.

PMID- 24744588
TI  - HLA variants related to primary sclerosing cholangitis influence rejection after
      liver transplantation.
AB  - AIM: To investigate influence of human leukocyte antigen (HLA) and killer
      immunoglobuline-like receptor (KIR) genotypes on risks of acute rejection (AR)
      after liver transplantation (LTX). METHODS: In this retrospective study we
      included 143 adult donor-recipient pairs with a minimum of 6 mo follow-up after
      LTX for whom DNA was available from both donor and recipients. Clinical data, all
      early complications including episodes and severity of AR and graft/patient
      survival were registered. The diagnosis of AR was based on clinical, biochemical
      and histological criteria. All suspected episodes of AR were biopsy confirmed.
      Key classical HLA loci (HLA-A, HLA-B, HLA-C and HLA-DRB1) were genotyped using
      Sanger sequencing. 16 KIR genes were genotyped using a novel real time PCR
      approach which allows for determination of the diploid copy number of each KIR
      gene. Immunohistochemical staining for T (CD3), B (CD20) and natural killer (NK)
      cells (CD56 and CD57) were performed on liver biopsies from 3 different patient
      groups [primary sclerosing cholangitis (PSC), primary biliary cirrhosis and non
      autoimmune liver disease], 10 in each group, with similar grade of AR. RESULTS:
      Fourty-four (31%) patients were transplanted on the basis of PSC, 40% of them had
      AR vs 24% in the non-PSC group (P = 0.04). No significant impact of donor
      recipient matching for HLA and KIR genotypes was detected. In the overall
      recipient population an increased risk of AR was detected for HLA-B*08 (P =
      0.002, OR = 2.5; 95%CI: 1.4-4.6), HLA-C*07 (P = 0.001, OR = 2.4; 95%CI: 1.4-4.0)
      and HLA-DRB1*03 (P = 0.03, OR = 1.9; 95%CI: 1.0-3.3) and a decreased risk for HLA
      DRB1*04 (P = 0.001, OR = 0.2; 95%CI: 0.1-0.5). For HLA-B*08, HLA-C*07 and DRB1*04
      the associations remained evident in a subgroup analysis of non-PSC recipients (P
      = 0.04, P = 0.003 and P = 0.02, respectively). In PSC recipients corresponding P
      values were 0.002, 0.17 and 0.01 for HLA-B*08, HLA-C*07 and DRB1*04,
      respectively. A dosage effect of AR prevalence according to the PSC associated
      HLA alleles was also notable in the total recipient population. For HLA-B*08 the
      frequency of AR was 56% in HLA-B*08 homozygous recipients, 39% in heterozygous
      recipients and 21% in recipients lacking HLA-B*08 (P = 0.02). The same was
      observed for the HLA-C*07 allele with AR in 57%, 27% and 18% in recipients being
      homozygous, heterozygous and lacking HLA-C*07 respectively (P = 0.003).
      Immunohistochemical analysis showed similar infiltration of T, B and NK cells in
      biopsies with AR in all three groups. CONCLUSION: We found significant
      associations between the PSC-associated HLA-B*08, HLA-C*07, HLA-DRB1*03 and HLA
      DRB1*04 alleles and risk of AR in liver transplant recipients.

PMID- 24744590
TI  - Immunohistochemical assessment of NY-ESO-1 expression in esophageal
      adenocarcinoma resection specimens.
AB  - AIM: To assess NY-ESO-1 expression in a cohort of esophageal adenocarcinomas.
      METHODS: A retrospective search of our tissue archive for esophageal resection
      specimens containing esophageal adenocarcinoma was performed, for cases which had
      previously been reported for diagnostic purposes, using the systematised
      nomenclature of human and veterinary medicine coding system. Original
      haematoxylin and eosin stained sections were reviewed, using light microscopy, to
      confirm classification and tumour differentiation. A total of 27 adenocarcinoma
      resection specimens were then assessed using immunohistochemistry for NY-ESO-1
      expression: 4 well differentiated, 14 moderately differentiated, 4 moderate
      poorly differentiated, and 5 poorly differentiated. RESULTS: Four out of a total
      of 27 cases of esophageal adenocarcinoma examined (15%) displayed diffuse
      cytoplasmic and nuclear expression for NY-ESO-1. They displayed a heterogeneous
      and mosaic-type pattern of diffuse staining. Diffuse cytoplasmic staining was not
      identified in any of these structures: stroma, normal squamous epithelium, normal
      submucosal gland and duct, Barrett's esophagus (goblet cell), Barrett's esophagus
      (non-goblet cell) and high grade glandular dysplasia. All adenocarcinomas showed
      an unexpected dot-type pattern of staining at nuclear, paranuclear and
      cytoplasmic locations. Similar dot-type staining, with varying frequency and size
      of dots, was observed on examination of Barrett's metaplasia, esophageal
      submucosal gland acini and the large bowel negative control, predominantly at the
      crypt base. Furthermore, a prominent pattern of apical (luminal) cytoplasmic dot
      type staining was observed in some cases of Barrett's metaplasia and also
      adenocarcinoma. A further morphological finding of interest was noted on
      examination of haematoxylin and eosin stained sections, as aggregates of
      lymphocytes were consistently noted to surround submucosal glands. CONCLUSION: We
      have demonstrated for the first time NY-ESO-1 expression by esophageal
      adenocarcinomas, Barrett's metaplasia and normal tissues other than germ cells.

PMID- 24744591
TI  - Positive predictors for gastroesophageal reflux disease and the therapeutic
      response to proton-pump inhibitors.
AB  - AIM: To identify objective and subjective predictors for the reliable diagnosis
      of gastroesophageal reflux disease (GERD) and the response to proton pump
      inhibitor (PPI) therapy. METHODS: Retrospectively, 683 consecutive patients
      suspected for GERD who underwent pH-metry/impedance measurement (pH/MII) were
      analyzed. All patients had previously undergone standard PPI treatment (e.g.,
      pantoprazole 40 mg/d or comparable). Four hundred sixty patients were at least 10
      d off PPIs (group A), whereas 223 patients were analyzed during their ongoing PPI
      therapy (group B). In addition, all patients completed a standardized symptom-
      and lifestyle-based questionnaire, including the therapeutic response to previous
      PPI trials on a 10-point scale. Uni- and multivariance analyses were performed to
      identify criteria associated with positive therapeutic response to PPIs. RESULTS:
      In group A, positive predictors (PPs) for response in empirical PPI trials were
      typical GERD symptoms (heartburn and regurgitation), a positive symptom index
      (SI) and pathological results in pH/MII, along with atypical symptoms, including
      hoarseness and fullness. In group B, regular alcohol consumption was associated
      with the therapeutic response. The PPs for pathological results in pH/MII in
      group A included positive SI, male gender, obesity, heartburn and regurgitation.
      In group B, the PPs were positive SI and vomiting. Analyzing for positive SI, the
      PPs were pathological pH and/or MII, heartburn regurgitation, fullness, nausea
      and vomiting in group A and pathological pH and/or MII in group B. CONCLUSION:
      Anamnestic parameters (gender, obesity, alcohol) can predict PPI responses. In
      non-obese, female patients with non-typical reflux symptoms, pH/MII should be
      considered instead of empirical PPIs.

PMID- 24744592
TI  - Non-small-bowel abnormalities identified during small bowel capsule endoscopy.
AB  - AIM: To investigate the incidence of non-small-bowel abnormalities in patients
      referred for small bowel capsule endoscopy, this single center study was
      performed. METHODS: Small bowel capsule endoscopy is an accepted technique to
      investigate obscure gastrointestinal bleeding. This is defined as bleeding from
      the digestive tract that persists or recurs without an obvious etiology after a
      normal gastroduodenoscopy and colonoscopy. Nevertheless, capsule endoscopy
      sometimes reveals findings outside the small bowel, i.e., within reach of
      conventional endoscopes. In this retrospective single center study, 595 patients
      undergoing capsule endoscopy between 2003 and 2009 were studied. The incidence of
      non-small bowel abnormalities was defined as visible abnormalities detected by
      capsule endoscopy that are located within reach of conventional endoscopes.
      RESULTS: In 595 patients, referred for obscure gastrointestinal bleeding or for
      suspected Crohn's disease, abnormalities were found in 306 (51.4%). Of these 306
      patients, 85 (27.7%) had abnormalities within reach of conventional endoscopes;
      63 had abnormalities apparently overlooked at previous conventional endoscopies,
      10 patients had not undergone upper and lower endoscopy prior to capsule
      endoscopy and 12 had abnormalities that were already known prior to capsule
      endoscopy. The most common type of missed lesions were vascular lesions (n = 47).
      Non-small-bowel abnormalities were located in the stomach (n = 15), proximal
      small bowel (n = 22), terminal ileum (n = 21), colon (n = 19) or at other or
      multiple locations (n = 8). Ten patients with abnormal findings in the terminal
      ileum had not undergone examination of the ileum during colonoscopy. CONCLUSION:
      A significant proportion of patients undergoing small bowel capsule endoscopy had
      lesions within reach of conventional endoscopes, indicating that capsule
      endoscopy was unnecessarily performed.

PMID- 24744593
TI  - Combined laparoscopic spleen-preserving distal pancreatectomy and islet
      autotransplantation for benign pancreatic neoplasm.
AB  - AIM: To evaluate the safety and feasibility of laparoscopic spleen-preserving
      distal pancreatectomy (LSPDP) with autologous islet transplantation (AIT) for
      benign tumors of the pancreatic body-neck. METHODS: Three non-diabetic, female
      patients (age 37, 44 and 35 years, respectively) were declared candidates for
      surgery, between May and September 2011, because of pancreatic body/neck cystic
      lesions. The planned operation was an LSPDP associated with AIT from the normal
      pancreas distal to the neoplasm. Islets isolation was performed on the residual
      pancreatic parenchyma after frozen section examination of the margin. Purified
      autologous islets were infused into the portal vein by a percutaneous
      transhepatic approach the day after surgery. RESULTS: The procedure was performed
      successfully in all the three cases, and the spleen was preserved along with its
      vessels. Mean operation time was 283 +/- 52 min and average blood loss was 133 +/
      57 mL. Residual pancreas weights were 33, 22 and 30 g, and 105.200, 40.390 and
      94.790 islet equivalents were isolated, respectively. Surgical complications
      occurred in one patient (grade A pancreatic fistula). Postoperative stays were 6,
      6 and 7 d, respectively. Histopathological evaluation revealed mucinous cystic
      neoplasm in cases 1 and 3, and serous cystic neoplasm in patient 2. No
      postoperative insulin administration was required. One patient developed a
      transient partial portal thrombosis 2 mo after islet infusion. Patients are
      insulin independent at a mean follow up of 8 +/- 2 mo. CONCLUSION: Combination of
      LSPDP and AIT is feasible and could be effective to minimize the surgical impact
      for benign neoplasm of pancreatic body-neck.

PMID- 24744594
TI  - Acute right lower abdominal pain in women of reproductive age: clinical clues.
AB  - AIM: To study possible gynecological organ pathologies in the differential
      diagnosis of acute right lower abdominal pain in patients of reproductive age.
      METHODS: Following Clinical Trials Ethical Committee approval, the retrospective
      data consisting of physical examination and laboratory findings in 290 patients
      with sudden onset right lower abdominal pain who used the emergency surgery
      service between April 2009 and September 2013, and underwent surgery and general
      anesthesia with a diagnosis of acute appendicitis were collated. RESULTS: Total
      data on 290 patients were obtained. Two hundred and twenty-four (77.2%) patients
      had acute appendicitis, whereas 29 (10%) had perforated appendicitis and 37
      (12.8%) had gynecological organ pathologies. Of the latter, 21 (7.2%) had ovarian
      cyst rupture, 12 (4.2%) had corpus hemorrhagicum cyst rupture and 4 (1.4%) had
      adnexal torsion. Defense, Rovsing's sign, increased body temperature and
      increased leukocyte count were found to be statistically significant in the
      differential diagnosis of acute appendicitis and gynecological organ pathologies.
      CONCLUSION: Gynecological pathologies in women of reproductive age are misleading
      in the diagnosis of acute appendicitis.

PMID- 24744595
TI  - Clinical study using novel endoscopic system for measuring size of
      gastrointestinal lesion.
AB  - AIM: To verify the performance of a lesion size measurement system through a
      clinical study. METHODS: Our proposed system, which consists of a conventional
      endoscope, an optical device, an optical probe, and a personal computer,
      generates a grid scale to measure the lesion size from an endoscopic image. The
      width of the grid scale is constantly adjusted according to the distance between
      the tip of the endoscope and lesion because the lesion size on an endoscopic
      image changes according to the distance. The shape of the grid scale was
      corrected to match the distortion of the endoscopic image. The distance was
      calculated using the amount of laser light reflected from the lesion through an
      optical probe inserted into the instrument channel of the endoscope. The
      endoscopist can thus measure the lesion size without contact by comparing the
      lesion with the size of the grid scale on the endoscopic image. (1) A basic test
      was performed to verify the relationship between the measurement error eM and the
      tilt angle of the endoscope; and (2) The sizes of three colon polyps were
      measured using our system during endoscopy. These sizes were immediately measured
      by scale after their removal. RESULTS: There was no error at alpha = 0 degrees .
      In addition, the values of eM (mean +/- SD) were 0.24 +/- 0.11 mm (alpha = 10
      degrees ), 0.90 +/- 0.58 mm (alpha = 20 degrees ) and 2.31 +/- 1.41 mm (alpha =
      30 degrees ). According to these results, our system has been confirmed to
      measure accurately when the tilt angle is less than 20 degrees . The measurement
      error was approximately 1 mm in the clinical study. Therefore, it was concluded
      that our proposed measurement system was also effective in clinical examinations.
      CONCLUSION: By combining simple optical equipment with a conventional endoscope,
      a quick and accurate system for measuring lesion size was established.

PMID- 24744596
TI  - Single hepatocellular carcinoma <= 3 cm in left lateral segment: liver resection
      or radiofrequency ablation?
AB  - AIM: To evaluate the long-term results of radiofrequency ablation (RFA) compared
      to left lateral sectionectomy (LLS) in patients with Child-Pugh class A disease
      for the treatment of single and small hepatocellular carcinoma (HCC) in the left
      lateral segments. METHODS: We retrospectively reviewed the data of 133 patients
      with single HCC (<= 3 cm) in their left lateral segments who underwent curative
      LLS (n = 66) or RFA (n = 67) between 2006 and 2010. RESULTS: The median follow-up
      period was 33.5 mo in the LLS group and 29 mo in the RFA group (P = 0.060). Most
      patients had hepatitis B virus-related HCC. The hospital stay was longer in the
      LLS group than in the RFA group (8 d vs 2 d, P < 0.001). The 1-, 2-, and 3-year
      disease-free survival and overall survival rates were 80.0%, 68.2%, and 60.0%,
      and 95.4%, 92.3%, and 92.3%, respectively, for the LLS group; and 80.8%, 59.9%,
      and 39.6%, and 98.2%, 92.0%, and 74.4%, respectively, for the RFA group. The
      disease-free survival curve and overall survival curve were higher in the LLS
      group than in the RFA group (P = 0.012 and P = 0.013, respectively). Increased
      PIVKA-II levels and small tumor size were associated with HCC recurrence in
      multivariate analysis. CONCLUSION: Liver resection is suitable for single HCC <=
      3 cm in the left lateral segments.

PMID- 24744597
TI  - YouTube as a source of patient information on gallstone disease.
AB  - AIM: To investigate the quality of YouTube videos on gallstone disease and to
      assess viewer response according to quality. METHODS: A YouTube search was
      performed on September 18, 2013, using the keywords ''gallbladder disease'',
      ''gallstone disease'', and ''gallstone treatment''. Three researchers assessed
      the source, length, number of views, number of likes, and days since upload. The
      upload source was categorised as physician or hospital (PH), medical website or
      TV channel, commercial website (CW), or civilian. A usefulness score was devised
      to assess video quality and to categorise the videos into ''very useful'',
      ''useful'', ''slightly useful'', or ''not useful''. Videos with misleading
      content were categorised as ''misleading''. RESULTS: One hundred and thirty-one
      videos were analysed. Seventy-four videos (56.5%) were misleading, 36 (27.5%)
      were slightly useful, 15 (11.5%) were useful, three (2.3%) were very useful, and
      three (2.3%) were not useful. The number of mean likes (1.3 +/- 1.5 vs 17.2 +/-
      38.0, P = 0.007) and number of views (756.3 +/- 701.0 vs 8910.7 +/- 17094.7, P =
      0.001) were both significantly lower in the very useful group compared with the
      misleading group. All three very useful videos were PH videos. Among the 74
      misleading videos, 64 (86.5%) were uploaded by a CW. There was no correlation
      between usefulness and the number of views, the number of likes, or the length.
      The "gallstone flush" was the method advocated most frequently by misleading
      videos (25.7%). CONCLUSION: More than half of the YouTube videos on gallstone
      disease are misleading. Credible videos uploaded by medical professionals and
      filtering by the staff of YouTube appear to be necessary.

PMID- 24744598
TI  - Efficacy and tolerability of low-dose interferon-alpha in hemodialysis patients
      with chronic hepatitis C virus infection.
AB  - AIM: To evaluate the efficacy and tolerability of low-dose standard or pegylated
      interferon (PEG-IFN) in hepatitis C virus (HCV)-positive hemodialysis patients.
      METHODS: In total, 19 patients were enrolled in this study, of which 12 received
      PEG-IFNalpha-2a 67.5 MUg 1 time/wk (Group 1) and 7 received standard interferon
      alpha-2b subcutaneously 1.5 * 106 U 3 times/wk (Group 2). The treatment durations
      were 48 wk for patients infected with HCV genotype 1 and 24 wk for patients
      infected with HCV genotype 2/3. All patients were prospectively followed after
      the completion of therapy. The efficacy and tolerability of the treatment were
      evaluated based on the sustained virological response (SVR) and treatment-related
      drop-out rate. RESULTS: In Group 1, 11 of the 12 patients completed the
      treatment. Early virological response (EVR) and sustained virological response
      (SVR) rates were 83.3% and 91.7%, respectively. One patient withdrew from
      treatment due to an adverse event (leukopenia). The drop-out rate was 8.3% in
      this group. In Group 2, 5 of the 7 patients completed the treatment with an EVR
      and SVR of 85.7% and 71.4%, respectively. Two patients withdrew due to treatment
      related adverse events (nausea and depression). In this group, the drop-out rate
      was 28.6%. In total, 16 of the patients attained EVR, and 15 of them completed
      the treatment. The SVR rate for the patients who attained EVR was 93.7%. Anemia
      was the most frequent side effect and was observed in 10/19 patients (55.5%), but
      could be effectively managed with erythropoietin. CONCLUSION: Low-dose interferon
      monotherapy, either with PEG-IFNalpha-2a or standard interferon alpha-2b, is an
      effective treatment option for hemodialysis patients with chronic hepatitis C.

PMID- 24744599
TI  - Clinical significance of nerve growth factor and tropomyosin-receptor-kinase
      signaling pathway in intrahepatic cholangiocarcinoma.
AB  - AIM: To investigate the correlation between nerve growth factor-tropomyosin
      receptor-kinase (NGF-TrkA) signaling pathway and prognosis in intrahepatic
      cholangiocarcinoma (IHCC). METHODS: NGF and TrkA expression in 83 samples of IHCC
      was assessed by immunohistochemistry. Correlations between NGF-TrkA expression
      and clinicopathological features were analyzed by chi2 test. Moreover, we
      evaluated the association between NGF-TrkA and overall survival by univariate and
      multivariate analysis. With experiments in vitro, we investigated the crucial
      role of NGF-TrkA on proliferation and invasion of IHCC cells with recombinant NGF
      beta stimulation. RESULTS: We found that NGF and TrkA expression was
      significantly related with differentiation (P = 0.024) and intraneural invasion
      (P = 0.003), respectively. Additionally, double higher expression of NGF and TrkA
      was identified as an independent prognostic factor in IHCC (P = 0.003). Moreover,
      we demonstrated that NGF-TrkA signaling pathway can promote IHCC proliferation
      and invasion. CONCLUSION: NGF-TrkA double higher expression is an independent
      prognostic factor in IHCC. NGF-TrkA pathway can promote IHCC progression,
      indicating that NGF-TrkA may become a potential drug target.

PMID- 24744601
TI  - Effect of precut sphincterotomy on post-endoscopic retrograde
      cholangiopancreatography pancreatitis: a systematic review and meta-analysis.
AB  - AIM: To conduct a systemic review and meta-analysis to investigate the role of
      early precut technique. Multiple randomized controlled trails (RCTs) have
      reported conflicting results of the early precut sphincterotomy. METHODS:
      MEDLINE/PubMed, EMBASE, Cochrane Central Register of Controlled Trials and
      Database of Systematic Reviews, and recent abstracts from major conference
      proceedings were searched (June 2013). Randomized and non-randomized studies
      comparing early precut technique with prolonged standard methods were included.
      Pooled estimates of post-endoscopic retrograde cholangiopancreatography (ERCP)
      pancreatitis (PEP), cannulation and adverse events were analyzed by using odds
      ratio (OR). Random and fixed effects models were used as appropriate. Publication
      bias was assessed by funnel plots. Heterogeneity among studies was assessed by
      calculating I2 measure of inconsistency. RESULTS: Seven randomized and seven non
      randomized trials met inclusion criteria. Meta-analysis of RCTs showed a decrease
      trend for PEP with early precut sphincterotomy but was not statistically
      significant (OR = 0.58; 95%CI: 0.32-1.05; P = 0.07). No heterogeneity was noted
      among the studies with I2 of 0%. CONCLUSION: Early precut technique for common
      bile duct cannulation decreases the trend of post-ERCP pancreatitis.

PMID- 24744600
TI  - Combined detection tumor markers for diagnosis and prognosis of gallbladder
      cancer.
AB  - AIM: To clarify the value of combined use of markers for the diagnosis of
      gallbladder cancer and prediction of its prognosis. METHODS: Serum cancer
      antigens (CA)199, CA242, carcinoembryonic antigen (CEA), and CA125 levels were
      measured in 78 patients with gallbladder cancer (GBC), 78 patients with benign
      gallbladder diseases, and 78 healthy controls using electrochemiluminescence.
      CA199, CA242, CEA, and CA125 levels and positive rates were analyzed and
      evaluated pre- and post-operatively. Receiver operator characteristic curves were
      used to determine diagnostic sensitivity and specificity of GBC. Survival time
      analysis, including survival curves, and multivariate survival analysis of a Cox
      proportional hazards model was performed to evaluate independent prognostic
      factors. RESULTS: Serum CA242, CA125, and CA199 levels in the GBC group were
      significantly higher when compared with those in the benign gallbladder disease
      and healthy control groups (P < 0.01). With a single tumor marker for GBC
      diagnosis, the sensitivity of CA199 was the highest (71.7%), with the highest
      specificity being in CA242 (98.7%). Diagnostic accuracy was highest with a
      combination of CA199, CA242, and CA125 (69.2%). CA242 could be regarded as a
      tumor marker of GBC infiltration in the early stage. The sensitivity of CA199 and
      CA242 increased with progression of GBC and advanced lymph node metastasis (P <
      0.05). The 78 GBC patients were followed up for 6-12 mo (mean: 8 mo), during
      which time serum CA199, CA125, and CA242 levels in the recurrence group were
      significantly higher than in patients without recurrence (P < 0.01). The post
      operative serum CA199, CA125, and CA242 levels in the non-recurrence group were
      significantly lower than those in the GBC group (P < 0.01). Multivariate survival
      analysis using a Cox proportional hazards model showed that cancer of the
      gallbladder neck and CA199 expression level were independent prognostic factors.
      CONCLUSION: CA242 is a marker of GBC infiltration in the early stage. CA199 and
      cancer of the gallbladder neck are therapeutic and prognostic markers.

PMID- 24744602
TI  - Simultaneous liver mucinous cystic and intraductal papillary mucinous neoplasms
      of the bile duct: a case report.
AB  - Cystic hepatic neoplasms are rare tumors, and are classified into two separate
      entities: mucinous cystic neoplasms (MCNs) and intraductal papillary mucinous
      neoplasms of the bile duct (IPMN-B). We report the case of a 56-year-old woman
      who presented with abdominal pain and jaundice due to the presence of a large
      hepatic multilocular cystic tumor associated with an intraductal tumor. Partial
      hepatectomy with resection of extrahepatic bile ducts demonstrated an
      intrahepatic MCN and an intraductal IPMN-B. This is the first report of the
      simultaneous occurrence of these two histologically distinct entities in the
      liver.

PMID- 24744603
TI  - Primary rectal squamous cell carcinoma treated with surgery and radiotherapy.
AB  - Primary squamous cell carcinoma of the rectum is a rare malignancy, and the
      discrete dual lesions of rectum are even rarer. There is currently no effective
      and satisfactory treatment for this disease. Here we report a case of an elderly
      female with bi-primary squamous cell carcinoma of the rectum treated with radical
      resection and radiotherapy. The patient is still alive 43 mo after the initial
      curative resection of the tumor. We suggest that surgery as the primary treatment
      followed by concomitant radiotherapy may be an effective protocol for elderly
      patients with rectal squamous cell carcinoma. 

PMID- 24744604
TI  - Prolonged small vessel vasculitis with colon mucosal inflammation as first
      manifestations of Behcet's disease.
AB  - Behcet's disease is a chronic, relapsing, systemic vasculitis of unknown
      aetiology. Patients present manifestations of gastrointestinal complications,
      including mouth lesions, small and large intestinal lesions, and vascular lesions
      in the abdomen. In some cases, the intestinal ulcers of patients with Behcet's
      disease are indistinguishable from those of Crohn's disease, tuberculosis,
      vasculitis and other diseases. In this article, we present a case of atypical
      Behcet's disease with a complicated medical history and multisystem damage, for
      the purpose of better management of this disease. 

PMID- 24744605
TI  - Specialization and Universals in the Development of Reading Skill: How Chinese
      Research Informs a Universal Science of Reading.
AB  - Understanding Chinese reading is important for identifying the universal aspects
      of reading, separated from those aspects that are specific to alphabetic writing
      or to English in particular. Chinese and alphabetic writing make different
      demands on reading and learning to read, despite reading procedures and their
      supporting brain networks that are partly universal. Learning to read
      accommodates the demands of a writing system through the specialization of brain
      networks that support word identification. This specialization increases with
      reading development, leading to differences in the brain networks for alphabetic
      and Chinese reading. We suggest that beyond reading procedures that are partly
      universal and partly writing-system specific, functional reading universals arise
      across writing systems in their adaptation to human cognitive abilities.

PMID- 24744606
TI  - Endogenous hydrogen peroxide production in the epithelium of the developing
      embryonic lens.
AB  - PURPOSE: Hydrogen peroxide (H2O2) is an endogenously produced reactive oxygen
      species (ROS) present in a variety of mammalian systems. This particular ROS can
      play dichotomous roles, being beneficial in some cases and deleterious in others,
      which reflects the level and location of H2O2 production. While much is known
      about the redox regulation of ROS by antioxidant and repair systems in the lens,
      little is known about the endogenous production of H2O2 in embryonic lens tissue
      or the physiologic relevance of endogenous H2O2 to lens development. This gap in
      knowledge exists primarily from a lack of reagents that can specifically detect
      endogenous H2O2 in the intact lens. Here, using a recently developed
      chemoselective fluorescent boronate probe, peroxyfluor-6 acetoxymethyl ester (PF6
      AM), which selectively detects H2O2 over related ROS, we examined the endogenous
      H2O2 signals in the embryonic lens. METHODS: Embryonic day 10 chick whole lenses
      in ex vivo organ culture and lens epithelial cells in primary culture were loaded
      with the H2O2 probe PF6-AM. To determine the relationship between localization of
      mitochondria with active membrane potential and the region of H2O2 production in
      the lens, cells were exposed to the mitochondrial probe MitoTracker Red CMXRos
      together with PF6-AM. Diphenyleneiodonium (DPI), a flavin inhibitor that blocks
      generation of intracellular ROS production, was used to confirm that the signal
      from PF6-AM was due to endogenous ROS production. All imaging was performed by
      live confocal microscopy. RESULTS: PF6-AM detected endogenous H2O2 in lens
      epithelial cells in whole lenses in ex vivo culture and in lens epithelial cells
      grown in primary culture. No endogenous H2O2 signal could be detected in
      differentiating lens fiber cells with this probe. Treatment with DPI markedly
      attenuated the fluorescence signal from the peroxide-specific probe PF6-AM in the
      lens epithelium, suggesting that basal generation of ROS occurs in this region.
      The lens epithelial cells producing an endogenous H2O2 signal were also rich in
      actively respiring mitochondria. CONCLUSIONS: PF6-AM can be used as an effective
      reagent to detect the presence and localization of endogenous H2O2 in live lens
      cells.

PMID- 24744607
TI  - Epithelial phenotype in total sclerocornea.
AB  - PURPOSE: To understand whether the epithelial phenotype in total sclerocornea is
      corneal or conjunctival in origin. METHODS: Four cases of total sclerocornea
      (male:female = 1:3; mean age = 5.4 +/- 4.3; 1-11 years old) who received
      penetrating keratoplasty (PKP) at our hospital between 2008 and 2011 were
      included. Corneal buttons obtained during PKP were used for transmission electron
      microscopy (TEM) as well as immunoconfocal microscopy for cytokeratins 3, 12, and
      13, goblet cell mucin MUC5AC, connexin 43, stem cell markers p63 and ABCG2,
      laminin-5, and fibronectin. RESULTS: After a mean follow-up period of 38.8 +/-
      14.0 (12-54) months, the grafts remained clear in half of the patients. TEM
      examination revealed a markedly attenuated Bowman's layer in the scleralized
      corneas, with irregular and variably thinned collagen lamellar layers, and
      disorganization and random distribution of collagen fibrils, which were much
      larger in diameter compared with a normal cornea. Immunoconfocal microscopy
      showed that keratin 3 was expressed in all four patients, while p63, ABCG2, and
      MUC5AC were all absent. Cornea-specific keratin 12 was universally expressed in
      Patients 1 to 3, while mucosa (including conjunctiva)-specific keratin 13 was
      negative in these patients. Interestingly, keratin 12 and 13 were expressed in
      Patient 4 in a mutually exclusive manner. Linear expression of laminin-5 in the
      basement membrane zone and similar expression of fibronectin were observed.
      CONCLUSIONS: The epithelia in total sclerocornea are essentially corneal in
      phenotype, but in the event of massive corneal angiogenesis, invasion by the
      conjunctival epithelium is possible.

PMID- 24744608
TI  - Efficient induction of productive Cre-mediated recombination in retinal pigment
      epithelium.
AB  - PURPOSE: To dissect gene functions in the retinal pigment epithelium (RPE), we
      previously generated a tetracycline-inducible RPE-specific Cre mouse line.
      Although this Cre mouse line was useful for several conditional gene targeting
      studies that were conducted by different laboratories, its potential has not been
      fully exploited, presumably due to a lack of knowledge or procedure for inducing
      Cre expression appropriately in this mouse line. The goal of the current study is
      to establish a procedure that will improve the reproducibility of Cre-mediated
      recombination in this mouse line. METHODS: Analysis of Cre expression and
      function was performed in double transgenic mice derived from inducible RPE
      specific Cre and Cre-activatable ROSA26 lacZ reporter mice. A tetracycline
      derivative, doxycycline, was supplied to mice intravitreally to induce Cre
      expression. Cre expression and function were examined with reverse transcription
      PCR, immunoblotting, immunostaining, and in situ enzymatic assay for beta
      galactosidase. Retinal integrity was examined with electroretinography and
      morphometry. RESULTS: Intravitreal Dox injection elevated Cre expression
      significantly and resulted in productive Cre-mediated recombination in
      approximately 60% of the RPE cells in this mouse line with no apparent change in
      retinal integrity. CONCLUSIONS: Our results suggest that productive Cre-mediated
      recombination in this mouse line can be induced efficiently with intravitreal Dox
      delivery, with no apparent Dox or Cre toxicity. Therefore, our inducible RPE
      specific Cre mice are suitable for Cre/lox-based gene activation and inactivation
      in adult RPE, which is critical to the effectiveness and suitability of this Cre
      mouse line in long-term studies requiring conditional gene targeting.

PMID- 24744609
TI  - Adeno-associated virus type 8 vector-mediated expression of siRNA targeting
      vascular endothelial growth factor efficiently inhibits neovascularization in a
      murine choroidal neovascularization model.
AB  - PURPOSE: To assess the feasibility of a gene therapeutic approach to treating
      choroidal neovascularization (CNV), we generated an adeno-associated virus type 8
      vector (AAV2/8) encoding an siRNA targeting vascular endothelial growth factor
      (VEGF), and determined the AAV2/8 vector's ability to inhibit angiogenesis.
      METHODS: We initially transfected 3T3 cells expressing VEGF with the AAV2/8
      plasmid vector psiRNA-VEGF using the H1 promoter and found that VEGF expression
      was significantly diminished in the transfectants. We next injected 1 MUl (3 *
      10(14) vg/ml) of AAV2/8 vector encoding siRNA targeting VEGF (AAV2/8/SmVEGF-2; n
      = 12) or control vector encoding green fluorescent protein (GFP) (AAV2/8/GFP; n =
      14) into the subretinal space in C57BL/6 mice. One week later, CNV was induced by
      using a diode laser to make four separate choroidal burns around the optic nerve
      in each eye. After an additional 2 weeks, the eyes were removed for flat mount
      analysis of the CNV surface area. RESULTS: Subretinal delivery of AAV2/8/SmVEGF-2
      significantly diminished CNV at the laser lesions, compared to AAV8/GFP (1597.3
      +/- 2077.2 versus 5039.5 +/- 4055.9 um(2); p<0.05). Using an enzyme-linked
      immunosorbent assay, we found that VEGF levels were reduced by approximately half
      in the AAV2/8/SmVEGF-2 treated eyes. CONCLUSIONS: These results suggest that
      siRNA-VEGF can be expressed across the retina and that long-term suppression of
      CNV is possible through the use of stable AAV2/8-mediated siRNA-VEGF expression.
      In vivo gene therapy may thus be a feasible approach to the clinical management
      of CNV in conditions such as age-related macular degeneration.

PMID- 24744610
TI  - Amniotic membrane-derived stem cells: immunomodulatory properties and potential
      clinical application.
AB  - Epithelial and mesenchymal cells isolated from the amniotic membrane (AM) possess
      stem cell characteristics, differentiation potential toward lineages of different
      germ layers, and immunomodulatory properties. While their expansion and
      differentiation potential have been well studied and characterized, knowledge
      about their immunomodulatory properties and the mechanisms involved is still
      incomplete. These mechanisms have been evaluated on various target cells of the
      innate and the adaptive system and in animal models of different inflammatory
      diseases. Some results have evidenced that the immunomodulatory effect of AM
      derived cells is dependent on cell-cell contact, but many of them have
      demonstrated that these properties are mediated through the secretion of
      suppressive molecules. In this review, we present an update on the described
      immunomodulatory properties of the derived amniotic cells and some of the
      proposed involved mechanisms. Furthermore, we describe some assays in animal
      models of different inflammatory diseases which reveal the potential use of these
      cells to treat such diseases. 

PMID- 24744611
TI  - Stem cell treatment for avascular necrosis of the femoral head: current
      perspectives.
AB  - Avascular necrosis (AVN) of the femoral head is a progressive disease that
      predominantly affects younger patients. Although the exact pathophysiology of AVN
      has yet to be elucidated, the disease is characterized by a vascular insult to
      the blood supply of the femoral head, which can lead to collapse of the femoral
      head and subsequent degenerative changes. If AVN is diagnosed in the early stages
      of the disease, it may be possible to attempt surgical procedures which preserve
      the hip joint, including decompression of the femoral head augmented with
      concentrated bone marrow. The use of autologous stem cells has shown promise in
      halting the progression of AVN of the femoral head, and subsequently preventing
      young patients from undergoing total hip arthroplasty. The purpose of this study
      was to review the current use of stem cells for the treatment of AVN of the
      femoral head. 

PMID- 24744612
TI  - Validity of arthroscopic measurement of glenoid bone loss using the bare spot.
AB  - PURPOSE: Our aim was to test the validity of using the bare spot method to
      quantify glenoid bone loss arthroscopically in patients with shoulder
      instability. METHODS: Twenty-seven patients with no evidence of instability (18
      males, nine females; mean age 59.1 years) were evaluated arthroscopically to
      assess whether the bare spot is consistently located at the center of the
      inferior glenoid. Another 40 patients with glenohumeral anterior instability who
      underwent shoulder arthroscopy (30 males, ten females; mean age 25.9 years) were
      evaluated for glenoid bone loss with preoperative three-dimensional computed
      tomography (3D-CT) and arthroscopic examination. In patients without instability,
      the distances from the bare spot of the inferior glenoid to the anterior (Da) and
      posterior (Dp) glenoid rim were measured arthroscopically. In patients with
      instability, we compared the percentage glenoid bone loss calculated using CT
      versus arthroscopic measurements. RESULTS: Among patients without instability,
      the bare spot could not be identified in three of 27 patients. Da (9.5+/-1.2 mm)
      was smaller than Dp (10.1+/-1.5 mm), but it was not significantly different.
      However, only 55% of glenoids showed less than 1 mm of difference between Da and
      Dp, and 18% showed more than 2 mm difference in length. The bare spot could not
      be identified in five of 40 patients with instability. Pearson's correlation
      coefficient showed significant (P<0.001) and strong (R (2)=0.63) correlation in
      percentage glenoid bone loss between the 3D-CT and arthroscopy method
      measurements. However, in ten shoulders (29%), the difference in percentage
      glenoid bone loss between 3D-CT and arthroscopic measurements was greater than
      5%. CONCLUSION: The bare spot was not consistently located at the center of the
      inferior glenoid, and the arthroscopic measurement of glenoid bone loss using the
      bare spot as a landmark was inaccurate in some patients with anterior
      glenohumeral instability. LEVEL OF EVIDENCE: Level II, prospective comparative
      study.

PMID- 24744613
TI  - Factors influencing visor use among players in the National Hockey League (NHL).
AB  - Eye, orbital, and facial injuries are significant risks to National Hockey League
      (NHL) players, and can be mitigated by the use of a partial visor - currently
      optional for all non-rookie players. The goal of the current study was to
      determine the overall use of visors among non-rookie NHL players in the 2013-2014
      season and assess factors influencing their uptake. This was an observational,
      cross-sectional study using active NHL rosters and demographic information
      obtained from the official NHL website. Visor use was determined based on in-game
      video or images at two different time points in the 2013-2014 season. The use of
      visors during the 2013-2014 season was 75.2% among non-rookie players. When
      rookies were included, the overall use of visors was 77.8%. Compared to Canadian
      born players, European players were significantly more likely to choose to wear a
      visor (odds ratio [OR] 3.48, 95% confidence interval [CI] 1.96-6.17). Players in
      the younger age-groups, particularly those younger than 24 years (OR 5.67, 95% CI
      2.52-5.76) and those between 24 and 28 years (OR 2.18, 95% CI 1.23-3.87), were
      more likely to wear a visor compared to older players. Overall, visor use
      continues to grow in the NHL independently of new legislation, and is more likely
      in younger players and those of European origin. 

PMID- 24744614
TI  - Respiratory disorders in endurance athletes - how much do they really have to
      endure?
AB  - Respiratory disorders are often a cause of morbidity in top level endurance
      athletes, more often compromising their performance and rarely being a cause of
      death. Pathophysiological events occurring during exercise, such as bronchospasm,
      are sometimes followed by clear pathological symptoms represented by asthma
      related to physical exertion or rarely by pulmonary edema induced by a strenuous
      effort. Both bronchospasm and the onset of interstitial edema induced by exercise
      cannot be considered pathological per se, but are more likely findings that occur
      in several healthy subjects once physical exhaustion during exertion has been
      reached. Consequently, we get a vision of the respiratory system perfectly
      tailored to meet the body's metabolic demands under normal conditions but which
      is limited when challenged by strenuous exercise, in particular when it happens
      in an unfavorable environment. As extreme physical effort may elicit a
      pathological response in healthy subjects, due to the exceeding demand in a
      perfectly functional system, an overview of the main tools both enabling the
      diagnosis of respiratory impairment in endurance athletes in a clinical and
      preclinical phase has also been described. 

PMID- 24744615
TI  - Comparison of transtibial and transportal techniques in drilling femoral tunnels
      during anterior cruciate ligament reconstruction using 3D-CAD models.
AB  - PURPOSE: The purpose of this study was to assess the differences in bone tunnel
      apertures between the trans-accessory medial portal (trans-AMP) technique and the
      transtibial (TT) technique in double-bundle anterior cruciate ligament
      reconstruction. The extent of ovalization and the frequency of overlap of the two
      tunnel apertures were compared. METHODS: The simulation of femoral tunnel
      drilling with the TT and the trans-AMP techniques was performed using three
      dimensional computer aided design models from two volunteers. The incidence angle
      of drilling against the intercondylar wall, the femoral tunnel position, the
      ovalization, and the overlap were analyzed. The aperture and location of the
      tunnels were also examined in real anterior cruciate ligament reconstruction
      cases (n=36). RESULTS: The surgical simulation showed that a lower drill incident
      angle induced by the TT technique made the apertures of two tunnels more
      ovalized, located anteromedial tunnels in a shallower position to prevent
      posterior wall blow out, and led to a higher frequency of tunnel overlap. The
      trans-AMP group had tunnel places within the footprint and had less ovalization
      and overlap. The results of analysis for tunnels in the clinical cases were
      consistent with results from the surgical simulation. CONCLUSION: In the TT
      technique, the shallow anteromedial tunnel location and more ovalized tunnel
      aperture can lead to a higher frequency of tunnel overlap. Compared with the TT
      technique, the trans-AMP technique was more useful in preparing femoral tunnels
      anatomically and avoiding tunnel ovalization and overlapping in double-bundle
      anterior cruciate ligament reconstruction.

PMID- 24744616
TI  - Post-traumatic knee osteoarthritis in the young patient: therapeutic dilemmas and
      emerging technologies.
AB  - Traumatic knee injury is common in young adults and strongly contributes to
      premature development of knee osteoarthritis (OA). Post-traumatic knee OA poses a
      therapeutic dilemma to the physician, since no known therapy has an acceptable
      safety profile, effectively relieves joint pain, and enjoys reasonable patient
      acceptance. Consequently, these young patients will ultimately be faced with the
      decision to either undergo surgical intervention, despite prosthesis durability
      concerns, or to continue with ineffective nonsurgical treatment. Emerging
      therapies, such as biologics, disease-modifying drugs, partial joint
      resurfacings, and minimally invasive joint-unloading implants are currently being
      studied to fill this therapeutic void in the young patient with post-traumatic
      knee OA. 

PMID- 24744617
TI  - Supportive care in hemato-oncology: a review in light of the latest guidelines.
AB  - Recent developments in cancer therapy have resulted in increases in treatment
      success rates and survival. One of thebasic goals of such therapy is improving
      patient quality of life. Chemotherapy protocols for solid or
      hematologicalmalignancies-most of which include multiple agents-negatively impact
      patient quality of life. Additionally, there havebeen developments in supportive
      care, which seeks to ameliorate or minimize the negative effects of
      chemotherapy.Herein we present a review and brief summarization of some of the
      agents used for supportive care in cancer patientsin light of the latest
      guidelines. 

PMID- 24744618
TI  - The Frequency of Mutations in Exon 11 of the c-kit Gene in Patients With
      Leukemia.
AB  - OBJECTIVE: To determine the frequency of mutations in exon 11 of the c-kit gene
      in patients with leukemia. MATERIAL AND METHODS: The study included 50 leukemia
      patients (31 with acute myeloid leukemia, 5 with acutelymphoblastic leukemia, 9
      with chronic myeloid leukemia, and 5 with chronic lymphocytic leukemia) that
      underwentPCR-SSCP, followed by direct DNA sequencing. RESULTS: In all, 28 of the
      leukemia patients were male and 22 were female, with a mean age of 31.88 years
      (range: 2-65years). In total, 20 mutations in 19 patients were identified,
      including Lys550Asn, Tyr568Ser, Ile571Thr, Thr574Pro,Gln575His, Tyr578Pro,
      Asp579His, His580Gln, Arg586Thr, Asn587Asp, and Arg588Met, as well as novel point
      mutationsat codons Ile563Lys, Val569Leu, Tyr570Ser, and Pro577Ser. Ile571Leu
      substitution was observed in 2 patients andTrp582Ser substitution was observed in
      3 patients. CONCLUSION: The results suggest that mutations in exon 11 of the c
      kit gene might be useful as molecular geneticmarkers for leukemia.

PMID- 24744619
TI  - Flow cytometric evaluation of cell cycle regulators (cyclins and cyclin-dependent
      kinase inhibitors) expressed on bone marrow cells in patients with chronic
      myeloid leukemia and multiple myeloma.
AB  - OBJECTIVE: The aim of this study was to use flow cytometry to analyze the
      expression of cell cycle-regulating elementswith low and high proliferative
      signatures in patients with malignant diseases. MATERIAL AND METHODS: Cyclin D,
      E, A, and B, and cyclin-dependent kinase inhibitor (CDKI) p16 and p21 levels
      weremeasured via flow cytometry in patients with chronic myeloid leukemia (CML)
      (n = 16) and multiple myeloma (MM)(n = 13), and in controls (n = 15). RESULTS:
      The distributions of the cell cycle S phase were 10, 63%, 6, 72% and 3, 59%; for
      CML, MM and controlpatients, respectively. Among all the cyclins expressed during
      the S phase, cyclin D expression was the lowest in the CMLpatients. Distribution
      of cyclins and CDKIs during the G2/M phase was similar in the MM and control
      groups, whereascyclin expression was similar during all 3 phases in the MM and
      CML groups. CONCLUSION: Elevated cyclin expression during cell cycle phases in
      the CML and MM patients was not associatedwith elevated CDKI expression. This
      finding may increase our understanding of the mechanisms involved in
      theetiopathogenesis of hematological malignancy.

PMID- 24744620
TI  - The role of multidetector computed tomography in the early diagnosis of invasive
      pulmonary aspergillosis in patients with febrile neutropenia undergoing
      hematopoietic stem cell transplantation.
AB  - OBJECTIVE: To evaluate vessel involvement and the role of multidetector computed
      tomography (MDCT) in the earlydiagnosis of invasive pulmonary aspergillosis (IPA)
      in patients with febrile neutropenia and antibiotic-resistant feverundergoing
      autologous bone morrow transplantation. MATERIAL AND METHODS: In all, 74
      pulmonary MDCT examinations in 37 consecutive hematopoietic stem
      celltransplantation patients with febrile neutropenia and clinically suspected
      IPA were retrospectively evaluated. RESULTS: Diagnosis of IPA was based on Fungal
      Infections Cooperative Group, and National Institute of Allergy andInfectious
      Diseases Mycoses Study Consensus Group criteria. In all, 0, 14, and 11 patients
      were diagnosed as proven,probable, and possible IPA, respectively. Among the 25
      patients accepted as probable and possible IPA, all had pulmonaryMDCT findings
      consistent with IPA. The remaining 12 patients were accepted as having fever of
      unknown origin (FUO)and had patent vessels based on MDCT findings.In the patients
      with probable and possible IPA, 72 focal pulmonary lesions were observed; in 41
      of the 72 (57%) lesionsvascular occlusion was noted and the CT halo sign was
      observed in 25 of these 41 (61%) lesions. Resolution of feveroccurred following
      antifungal therapy in 19 (76%) of the 25 patients with probable and possible IPA.
      In all, 6 (25%)of the patients diagnosed as IPA died during follow-up. Transplant
      related mortality 100 d post transplant in patientswith IPA and FUO was 24% and
      0%, respectively. CONCLUSION: In conclusion, MDCT has a potential role in the
      early diagnosis of IPA via detection of vessel occlusion.

PMID- 24744621
TI  - The Association Between HLA Class II Alleles and the Occurrence of Factor VIII
      Inhibitor in Thai Patients with Hemophilia A.
AB  - OBJECTIVE: This study aimed to investigate the association between HLA class II
      alleles and the occurrence of FVIIIinhibitor in Thai hemophilia A patients.
      MATERIAL AND METHODS: The distribution of HLA-DRB1 alleles and DQB1 alleles in 57
      Thai hemophilia A patientsand 36 blood donors as controls was determined using
      the PCR sequence-specific primer (PCR-SSP) method, and theassociation between the
      occurrence of factor VIII (FVIII) inhibitor and the presence of certain HLA class
      II alleles wasinvestigated. RESULTS: The frequency of HLA-DRB1*15 was higher in
      the hemophilia A patients with and without FVIII inhibitor,whereas that of
      DRB1*14, DRB1*07, and DQB1*02 was lower in the hemophilia A patients with FVIII
      inhibitor, ascompared to controls. Interestingly, only the frequency of DRB1*15
      was significantly higher in the patients with inhibitorthan in the controls (P =
      0.021). Moreover, the frequency of DRB1*15 in the patients with inhibitor was
      higher than inthose without inhibitor (P = 0.198). CONCLUSION: The study's
      findings show that the DRB1*15 allele might have contributed to the occurrence of
      inhibitorin the Thai hemophilia A patients; however, additional research using
      larger samples and high-resolution DRB1 typingis warranted.

PMID- 24744622
TI  - The evaluation of fibrin sealants and tissue adhesives in oral surgery among
      patients with bleeding disorders.
AB  - OBJECTIVE: The aim of this study was to evaluate the efficiency of two local
      hemostatic agents administered with apreoperative dose of replacement therapy in
      patients with bleeding disorders undergoing oral surgery. MATERIAL AND METHODS:
      The study included 21 patients that were randomly divided into 3 groups. Patients
      in Group1 (n = 7) received preoperative replacement therapy and postoperative
      fibrin sealant applied to the surgical site. Patientsin Group 2 (n = 7) received
      preoperative replacement therapy and postoperative tissue adhesive applied to the
      surgicalsite. Patients in Group 3 (n = 7) were given replacement therapy pre- and
      postoperatively. RESULTS: Postoperative bleeding was not observed in 17 of the 21
      patients, including 5 in Group 1 (71.42%), 6 in Group2 (85.71%), and 6 in Group 3
      (85.71%). Hemorrhagic complications occurred in only 4 of the 21 patients.
      CONCLUSION: The use of fibrin sealant and tissue adhesive was beneficial, as they
      reduced the level of factor concentratesused for replacement therapy and resulted
      in rapid hemostasis at the surgical site, facilitating the ability to
      performserial surgical procedures concurrently.

PMID- 24744623
TI  - Rare coagulation disorders: a retrospective analysis of 156 patients in Turkey.
AB  - OBJECTIVE: To retrospectively evaluate the clinical findings, laboratory data,
      management, and outcome in a group ofTurkish children diagnosed with rare
      coagulation deficiencies (RCDs) between January 1999 and June 2009. MATERIAL AND
      METHODS: The Turkish Society of Pediatric Hematology-Hemophilia-Thrombosis
      Hemostasissubcommittee designed a Microsoft Excel-based questionnaire for
      standardized data collection and sent it to participatinginstitutions. RESULTS:
      In total, 156 patients from 12 pediatric referral centers were included in the
      study. The cost common RCDswere as follows: FVII (n = 53 [34%]), FV (n = 24
      [15.4%]), and FX (n = 23 [14.7%]) deficiency. The most common initialfinding in
      the patients was epistaxis, followed by ecchymosis, and gingival bleeding.
      CONCLUSION: Initial symptoms were mucosal bleeding, and fresh frozen plasma (FFP)
      and tranexamic acid werethe most commonly used treatments. We think that
      prophylactic treatment used for hemophilia patients should beconsidered as an
      initial therapeutic option for patients with rare factor deficiencies and a
      severe clinical course, and forthose with a factor deficiency that can lead to
      severe bleeding.

PMID- 24744624
TI  - The Effects of Endothelial Protein C Receptor Gene Polymorphisms on the Plasma
      sEPCR Level in Venous Thrombosis Patients.
AB  - OBJECTIVE: The aim of this study was to investigate variations in the endothelial
      cell protein C receptor gene (EPCRgene) that may play a role in thrombosis and
      the effects of these variations on the plasma soluble endothelial cell proteinC
      receptor (sEPCR) level in Turkish patients with venous thrombosis. MATERIAL AND
      METHODS: This study included 111 thrombosis patients and 73 healthy controls.
      Following DNAextraction, PCR, SSCP, and DNA sequencing analysis of 4 exons of the
      EPCR gene was performed. Plasma sEPCR wasmeasured via enzyme-linked immunosorbent
      assay (ELISA). RESULTS: In all, 3 polymorphisms were detected in exons 1-4.
      C3998T (SNP no: rs2069952) polymorphism was detectedin intron 2 and C4678G (A1
      haplotype) (SNP no: rs9574) in the 3' untranslated region (3'UTR). There weren't
      anysignificant differences in C3998T polymorphism between the control and patient
      groups. There wasn't a significantdifference in plasma sEPCR levels between both
      controls and patients that carried the A1 allele. A4600G substitution
      (A3haplotype) (SNP no: rs867186) was observed in exon 4 and was associated with a
      2.04-fold higher risk of thrombosis.A3 allele carriers had higher sEPCR levels
      than those without the allele. Mean sEPCR level in the patients with
      thehomozygous A3 allele was 289 ng MUL-1, versus 113.42 ng MUL-1 in those with
      the homozygous A1 allele. CONCLUSION: The A1 haplotype might offer protection
      against thrombosis and the A3 haplotype might be associatedboth with elevated
      plasma sEPCR and elevated risk of venous thrombosis in the Turkish population.
      Plasma sEPCRlevels were significantly higher in those that carried the A3 allele
      (4600A>G) (both patients and controls). Among theparticipants that carried the A1
      allele (4678C>G), plasma sEPCR did not differ significantly.

PMID- 24744625
TI  - How Does Influenza A (H1N1) Infection Proceed in Allogeneic Stem Cell
      Transplantation Recipients?
AB  - The clinical course of influenza A (H1N1) infection in allogeneic hematopoietic
      stem cell transplantation (AHSCT)recipients is not clearly known. We report 3
      AHSCT recipients that were infected with influenza A (H1N1). Each of thepatients
      had a different hematological disease and was at a different post-transplantation
      stages. All the patients weretreated with oseltamivir, and zanamivir was switched
      to oseltamivir in 1 patient. All the patients survived without anycomplications.
      The course of swine flu can vary and progress with bacterial or other viral
      infections in immunosuppressedpatients. 

PMID- 24744626
TI  - H1N1-Associated Encephalitis in a Child with Acute Myeloblastic Leukemia and
      Bacteremia due to Klebsiella Pneumoniae.
AB  - Herein we present a neutropenic 16-year-old female with acute myeloblastic
      leukemia that developed recurrentgeneralized seizures while receiving
      antimicrobial therapy (including oseltamivir) due to pneumonia, bacteremiaof
      Klebsiella pneumoniae, and H1N1 infection. The patient's seizures were controlled
      using assisted ventilation.Electroencephalography showed that the patient had
      encephalopathy. Cranial computed tomography (CT), magneticresonance imaging
      (MRI), and MRI angiography findings were normal. The patient fully recovered
      without sequelae.This case indicates that during pandemics of influenza-like
      diseases H1N1 infection should always be a consideration. 

PMID- 24744627
TI  - Hydrops Fetalis due to Kell Alloimmunization: A Perinatal Approach to a Rare
      Case.
AB  - OBJECTIVE: While routine administration of rhesus (Rh) immunoglobulin has
      significantly reduced the incidence of Rh alloimmunization, maternal
      alloimmunization to other red cell antigens remains a contributor to perinatal
      morbidity and mortality. Although the Kell antigen is seen on the red cells of
      only 9% of the general population, attention to Kell antibodies continues to
      increase. CASE REPORT: A case of fetal hydrops was sonographically detected at 30
      weeks of gestation. Antenatal tests to evaluate the fetus's condition clearly
      showed that the level of hemolytic disease was critical and the baby was
      delivered prematurely due to fetal distress. The combination of anemia,
      reticulocytopenia, hydrops fetalis, and a positive indirect Coombs test suggested
      Kell isoimmunization. The baby was successfully treated with exchange transfusion
      of Kellnegative packed red cells, and was discharged on postnatal d 30.
      CONCLUSION: The presented case of hydrops fetalis was due Kell alloimmunization
      that was detected during the postnatal period, and thus we plan to discuss the
      perinatal approach to Kell immunization.

PMID- 24744628
TI  - Mercury toxicity: a family case report.
AB  - BACKGROUND: Environmental pollution exposes humans to toxic substances. Herein we
      present 5 family members aged20-54 years that were poisoned by liquid mercury.
      CASE REPORTS: Case 1 presented to our clinic with cough, fever, and night sweats.
      The patient had neutropenia, anemia,and pneumonia, rapidly developed acute
      respiratory distress syndrome (ARDS), and died on day 4 of hospitalization.Her
      WBC count was 0.4 * 103 mm-3 (normal range: 4.3-10.3 * 103 mm-3) and Hb was 10.8
      g dL-1 (normal range: 11.5-16.0 g dL-1). Case 2 presented with bicytopenia; the
      leukocyte count was 1.3 * 103 mm-3 (normal range: 4.3-10.3 * 103mm-3) and the PLT
      count was 88 * 103 mm-3 (normal range: 150-400 * 103 mm-3). Cases 2 and 3 had
      toxic peripheralneuropathy. The PLT count in case 3 was 123 * 103 mm-3 (normal
      range: 150-400 * 103 mm-3). Cases 4 and 5 presentedwith fatigue and headache;
      these 2 patients did not have positive findings, apart from high levels of
      mercury in theblood. We have written informed consent. CONCLUSION: We think that
      heavy metal exposure-although rare-should be considered in patients that present
      withnumerous symptoms involving multiple systems, including the cardiovascular,
      respiratory, and neurological systems.The present report is unique in that in
      describes mercury poisoning in 5 members of the same family.

PMID- 24744629
TI  - Pancytopenia: an etiological profile.

PMID- 24744630
TI  - Flow cytometry: a rapid and robust adjuvant technique for pathological diagnosis.

PMID- 24744631
TI  - Corneal Epithelial Microcysts due to High-Dose Cytarabine Administration in a
      Pediatric Acute Myeloid Leukemia Patient.

PMID- 24744632
TI  - Blood donation: survey results.

PMID- 24744633
TI  - Endothelial Protein C Receptor gene Expression in a Female with Homozygous EPCR
      gene 23-bp Insertion.

PMID- 24744634
TI  - Rituximab therapy for refractory autoimmune thrombocytopenia in patients with
      systemic lupus erythematosus.

PMID- 24744635
TI  - Early profound secondary autoimmune thrombocytopenia induced by clopidogrel in a
      patient with a coronary artery stent.

PMID- 24744636
TI  - The incidence of alpha-thalassemia in iraqi turks.

PMID- 24744637
TI  - ABO and Rh Blood Group Distribution in Kayseri Province, Turkey.

PMID- 24744638
TI  - Did the proband have thalassemia intermedia or severe thalassemia trait?

PMID- 24744639
TI  - Primary Pleural Diffuse Large B-cell non-Hodgkin's Lymphoma Diagnosed via [18F]-2
      Fluoro-Deoxy-DGlucose Positron Emission Tomography /Computed Tomography.

PMID- 24744640
TI  - Bullous Cutaneous Eruption due to Extravasation of Acyclovir in an Adolescent
      with Acute Lymphoblastic Leukemia.

PMID- 24744641
TI  - Inflammatory bowel disease and thrombosis.
AB  - Inflammatory Bowel Disease (IBD) is a group of chronic and relapsing inflammatory
      disorders of the gastrointestinalsystem. In these cases, findings are detected in
      extraintestinal systems also. There is a tendency for thrombotic eventsin IBD, as
      in the other inflammatory processes. The pathogenesis of this thrombotic tendency
      is multidimensional,including lack of natural anticoagulants, prothrombotic media
      induced via the inflammatory process, long-termsedentary life style, steroid use,
      surgery, and catheter placement. The aim of this review was to highlight the
      positiverelationship between IBD and thrombotic events, and the proper treatment
      of at-risk patients. 

PMID- 24744642
TI  - The frequency and clinical relevance of multidrug resistance protein expression
      in patients with lymphoma.
AB  - OBJECTIVE: Multidrug resistance is a cause of treatment failure in patients with
      malignant lymphoma; however, the frequency and clinical relevance of multidrug
      resistance protein expression are unclear. The present study aimed to investigate
      expression of the most common multidrug resistance proteins in a group of
      lymphoma patients. MATERIAL AND METHODS: The study included 44 previously
      untreated lymphoma patients (non-Hodgkin's lymphoma [n = 21], non-malignant
      lymphadenopathy [n = 13], and Hodgkin's lymphoma [n = 10]). MDR1, MRP, and LRP
      expression was assessed via quantitative PCR of lymph node biopsy specimens.
      RESULTS: In the non-Hodgkin's lymphoma group MDR1 was positive in 23.8% (5/21) of
      the patients, MRP was positive in 57.14% (12/21), and LRP was positive in 90.47%
      (19/21). In the non-malignant lymphadenopathy group, MDR1 was positive in 46.15%
      (6/13) of the patients, MRP was positive in 84.61% (11/13), and LRP was positive
      in 100% (13/13). In the Hodgkin's lymphoma group MDR1 was positive in 50% (5/10)
      of the patients, MRP was positive in 50% (5/10), and LRP was positive in 80%
      (8/10). MDR1, MRP, and LRP expression did not differ between the 3 groups.
      Furthermore, MDR1, MRP, and LRP expression wasn't associated with tumor stage,
      response to first-line therapy, the erythrocyte sedimentation rate, or C reactive
      protein, beta 2 microglobulin, serum lactate dehydrogenase, and albumin levels.
      Additionally, survival time in the MDR1- and MRP-positive, and MDR1- and MRP
      negative patients did not differ (comparison of LRP was not possible due to the
      small number of LRP-negative patients). CONCLUSION: According to the present
      findings, future studies should investigate alternative pathways of multidrug
      resistance in order to arrive at a better understanding of treatment failure in
      lymphoma patients.

PMID- 24744643
TI  - Molecular Evaluation of t(14;18)(bcl-2/IgH) Translocation in Follicular Lymphoma
      at Diagnosis Using Paraffin-Embedded Tissue Sections.
AB  - OBJECTIVE: Follicular lymphoma (FL) is one of the most common lymphomas, and is
      characterized by t(14;18)(q32;q21) in more than 80% of patients. The aim of this
      study was to determine the rate of t(14;18) positivity based onthe detection of
      mbr or mcr in paraffin-embedded tissue samples. MATERIAL AND METHODS: The study
      included 32 paraffin-embedded tissue samples collected from 32 consecutive FL
      patients that were diagnosed and followed-up at our hospital between 1999 and
      2006. The MBR breakpoint wasidentified based on real-time PCR using a LightCycler
      v.2.0 t(14;18) Quantification Kit (MBR), multiplex PCR, and seminestedPCR. To
      identify the mcr breakpoint, real-time PCR was performed using specific primers
      and the FastStart DNAMaster SYBR Green I Kit. To detect t(14;18) via fluorescence
      in situ hybridization (FISH) nuclei from paraffin-embeddedtissue sections were
      extracted and used together with LSI IgH (immunoglobulin heavy chain) (spectrum
      green)/bcl-2(B-cell leukemia-lymphoma 2) (spectrum orange) probes. RESULTS: The
      DNA and nuclei isolation success rate for B5 formalin-fixed, paraffin-embedded
      tissue sections (n = 12)was 42% and 33%, respectively, versus 95% and 60%,
      respectively, for 20 tissue sections fixed in formalin only. In all,24 paraffin
      embedded tissue sections were analyzed and mbr positivity was observed in the DNA
      of 82.14% via seminested PCR, in 53.57% via multiplex PCR, and in 28.57% via real
      time PCR. We did not detect mcr rearrangementin any of the samples. In all, 15 of
      16 patients (93.75%) whose nuclei were successfully isolated were observed to
      bet(14;18) positive via the FISH method. CONCLUSION: Semi-nested PCR and FISH
      facilitated the genetic characterization of FL tumors. As such, FISH and PCR
      complement each other and are both essential for detecting t(14;18)
      translocation.

PMID- 24744644
TI  - Conventional and molecular cytogenetic analyses in Turkish patients with multiple
      myeloma.
AB  - OBJECTIVE: Multiple myeloma (MM) is characterized by the accumulation and
      proliferation of malignant plasma cells, secreting monoclonal immunoglobulins and
      genetic abnormalities in MM have implications for disease progression and
      survival. In the present study, we investigated the frequency of chromosomal
      abnormalities (CA) in Turkish patients with MM, using interphase FISH and CC and
      evaluated the relationship between the rearrangements detected, prognosis and
      stage of disease. MATERIAL AND METHODS: We performed conventional cytogenetic and
      FISH studies in 50 patients to detect chromosome anomalies associated with MM.
      FISH probes were used to detect 13q14, 13q34, 17p13 deletions, IGH
      rearrangements, and monosomy and/or trisomy of chromosomes 5, 9, and 15. RESULTS:
      CC studies could be performed in 32 of 50 cases and five patients (15.6%) showed
      chromosomal aberrations while 27 (84.3%) had normal karyotypes. By FISH, eighteen
      percent (9/50) of cases were found to be normal for all parameters evaluated.
      Eighty-two percent (41/50) of the patients were positive for at least one
      abnormality. Chromosome 13 anomalies were detected in 54% (27/50) of cases. The
      second most common aberration observed is chromosome 15 aberrations (50%).
      CONCLUSION: Median survival rate was shorter in patients with one of the
      abnormalities including chromosome 13 aberrations, IGH rearrangements or P53
      deletions. Chromosome 15 aberrations were significantly higher in patients with
      stage III disease (p=0.02). We conclude that FISH studies should be performed in
      conjunction with conventional cytogenetic analysis for prognosis in multiple
      myeloma patients.

PMID- 24744645
TI  - Hematopoietic stem cell transplantation activity and trends at a pediatric
      transplantation center in Turkey during 1998-2008.
AB  - OBJECTIVE: The aim of this study was to document hematopoietic stem cell
      transplantation (HSCT) activity and trends at our treatment center. MATERIAL AND
      METHODS: Data collected over a 10-year period were retrospectively analyzed,
      concentrating primarily on types of HSCT, transplant-related mortality (TRM),
      stem cell sources, indications for HSCT, and causes of death following HSCT.
      RESULTS: In total, 222 allogeneic (allo)-HSCT (87.4%) and 32 autologous (auto)
      HSCT (12.6%) procedures were performed between 1998 and 2008. Stem cells obtained
      from unrelated donors were used in 22.6% (50/222) of the allo- HSCTs. Cord blood
      was the source of hematopoietic stem cells (HSC) in 12.2% of all transplants. The
      most common indication for allo-HSCT was hemoglobinopathy (43.2%), versus
      neuroblastoma (53.1%) for auto-HSCT. The TRM rate 1 year post transplantation was
      18.3% +/- 2.5% for all transplants, but differed according to transplantation
      type (23.5% +/- 7.9% for auto-HSCT and 17.5% +/- 2.6% for allo-HSCT). The most
      common cause of death 1 year post HSCT was infection (35.9%). CONCLUSION: The TRM
      rate in the patients that underwent allo-HSCT was similar to that which has been
      previously reported; however, the TRM rate in the patients that underwent auto
      HSCT was higher than previously reported in developed countries. The selection of
      these patients to be transplanted must be made attentively.

PMID- 24744646
TI  - Immunosuppressive treatment in children with acquired aplastic anemia.
AB  - OBJECTIVE: Immunosuppressive treatment (IST) is an alternative for children with
      acquired aplastic anemia (AA) that do not have HLA-matched donors. The objective
      of this study was to evaluate the outcome of IST in children with acquired AA.
      MATERIAL AND METHODS: The study included 18 pediatric acquired AA patients that
      were retrospectively evaluated. The patients either did not have an HLA-matched
      related donor or were unable to undergo transplantation within 6 months despite
      having an HLA-matched donor. RESULTS: In all, 6 of the patients were
      characterized as very severe AA, 6 as severe AA, and 6 as moderate AA. Mean
      duration of follow-up was 44.5 months. In total, 9 patients that could not be
      treated with equine anti-thymocyte globulin (hATG) following diagnosis received
      high-dose methylprednisolone treatment. Among the 6 very severe AA patients, 2
      achieved complete remission (22%); the other 16 patients received
      hATG+cyclosporine and short-term methylprednisolone. In total, 4 of the patients
      died during the first month of treatment. Of the remaining 12 patients, 3
      responded to the treatment (25%). Of the 9 patients that did not respond after 3
      months of treatment, 7 received a second course of immunosuppressive treatment
      with rabbit ATG (rATG)+cyclosporine and short-term methylprednisolone; 2 of the 7
      patients responded (22%), but 5 did not respond to any treatment. Median survival
      among the patients was as 64 +/- 8 months CONCLUSION: Combination IST with
      ATG+cyclosporine and low-dose methylprednisolone was an effective treatment in
      the pediatric acquired AA patients with non-identical HLA donors. In the patients
      that couldn't be treated with ATG high-dose methylprednisolone treatment was safe
      and effective.

PMID- 24744647
TI  - Torque teno virus and hepatitis C virus co-infection in Iranian pediatric
      thalassemia patients.
AB  - OBJECTIVE: Torque teno virus (TTV) infects patients at risk for parenteral
      exposure and chronic blood transfusion, such as those with beta-thalassemic. This
      study aimed to assess the prevalence of TTV infection and co-infection of TTV and
      hepatitis C virus (HCV) in pediatric thalassemia patients receiving chronic blood
      transfusion. MATERIAL AND METHODS: The study included 90 pediatric thalassemia
      patients receiving chronic blood transfusion that presented to the Mofid
      Children's Hospital, Tehran, Iran. The control group included 90 healthy
      volunteer children. Serum TTV DNA detection via semi-nested PCR and HCV Ab were
      performed in all the participants. Demographic characteristics and clinical data
      were collected from each participant for statistical analysis. RESULTS: In all,
      64.4% of the patients had TTV infection, versus 24.4% of the controls (P < 0.01).
      The thalassemia patients had a greater probability of having TTV and HCV
      infections than the controls, with a common OR of 5.60 (95% CI: 2.94-10.69) and
      2.15 (95% CI: 1.83-2.50), respectively. In total, 17.2% (10/58) of the patients
      that were TTV positive were also HCV positive, whereas 6.3% (2/32) of the TTV
      negative patients were anti-HCV antibody (Ab) positive (P = 0.14). CONCLUSION:
      The prevalence of TTV and HCV infection was higher in the Iranian thalassemia
      patients on chronic transfusion therapy than in the controls. The high prevalence
      of TTV in pediatric thalassemia patients on chromic transfusion therapy may
      indicate the superiority of the parenteral route compared to other routs of TTV
      transmission.

PMID- 24744649
TI  - Successful treatment with propranolol in a patient with a segmental hemangioma: a
      case report.
AB  - The treatment of hemangiomas in infancy may be associated with significant
      morbidity. In addition to morbidity, an objective response cannot be obtained
      because of the absence of targeted therapeutic options. Herein, we present an
      infant with a segmental hemangioma and marked glucocorticoid toxicity due to
      prior steroid therapy that was successfully treated with propranolol. Propranolol
      was tolerated well and no side effects were observed during the treatment. The
      only problem to occur was disease recurrence following the withdrawal of
      propranolol at age 13 months, which was not within the age of spontaneous
      regression (generally considered as >18 months). 

PMID- 24744648
TI  - The association between gene polymorphisms and leukocytosis with thrombotic
      complications in patients with essential thrombocythemia and polycythemia vera.
AB  - OBJECTIVE: Vascular events are a common complication in patients with
      polycythemia vera (PV) and essential thrombocythemia (ET). This study aimed to
      analyze the association between PAI-1 4G/5G and ACE I/D gene polymorphisms, and
      leukocytosis with thrombosis in patients with PV and ET. MATERIAL AND METHODS: In
      total, 64 patients with ET and PV were evaluated. Arterial or venous thrombosis,
      such as cerebral transient ischemic attack, ischemic stroke, myocardial
      infarction, peripheral arterial thrombosis, deep venous thrombosis, and pulmonary
      embolism, were defined as a vascular event. DNA samples were screened for
      mutations via reverse hybridization strip assay. RESULTS: In terms of PAI-1 gene
      polymorphism, the frequency of the 4G and 5G allele was 48.5% and 51.5%,
      respectively. The ACE allele frequency was 51.2% and 48.8% for D and I,
      respectively. There wasn't an association between occurrence of vascular events
      and the frequency of any allele. In terms of occurrence of vascular events, there
      weren't any significance differences between the patients that were carrying the
      ACE D/D homozygous allele to ACE I/D and those that carried the I/I allele (P =
      0.93). There wasn't a significant difference in occurrence of vascular events
      between the PAI-1 5G/5G homozygote allele carriers, and the 4G/5G and 4G/4G
      allele carriers (P = 0.97). Vascular events were significantly more common in the
      patients with leukocytosis (leukocyte count >10 * 109 L-1) than in those without
      leukocytosis (leukocyte count <=10 * 109 L-1) (P = 0.00). Age >60 years was also
      a significant risk factor for occurrence of vascular events(P = 0.008).
      CONCLUSION: PAI-1 and ACE gene polymorphisms were not considered new risk factors
      for thrombosis in PV and ET patients. On the other hand, leukocytosis at
      diagnosis was associated with the occurrence of vascular events in the patients
      with ET and PV.

PMID- 24744650
TI  - Is Swine-origin Influenza a Predisposing Factor for Deep Vein Thrombosis?
AB  - Herein we report a sixteen-year-old female that developed deep vein thrombosis
      (DVT) while undergoing treatment for H1N1 pneumonia. To the best of our knowledge
      this is the first report of H1N1/09 infection complicated by DVT in an adolescent
      patient with no detected risk factors other than immobilization. Healthcare
      providers should be aware of the possibility of thrombosis in patients with swine
      origin influenza, especially in those with additional risk factors. 

PMID- 24744651
TI  - Cerebellar granulocytic sarcoma: a case report.
AB  - Granulocytic sarcoma is a rare tumor composed of immature granulocytic cells that
      is usually associated with acute myelogenous leukemia. Intraparenchymal cranial
      localization without skull, meningeal, or bone marrow invasion is extremely rare.
      The mechanisms of intraparenchymal cranial localization of GS remains unknown, as
      only 10 cases with cerebellar granulocytic sarcoma have been previously reported.
      Herein, we report a four year old boy with cerebellar localization of
      granulocytic sarcoma. 

PMID- 24744652
TI  - Unilateral exudative retinal detachment as the sole presentation of relapsing
      acute lymphoblastic leukemia.
AB  - Ocular findings are rarely the initial symptom of leukemia, although up to 90% of
      all leukemia patients have fundus changes during the course of the disease.
      Herein we report a relapsing acute lymphoblastic leukemia patient with thesole
      presentation of sudden visual loss and exudative retinal detachment. An 8-year
      old boy with acute lymphoblasticleukemia developed sudden visual loss during his
      first remission period. Bullous retinal detachment with total afferentpupillary
      defect was observed. Orbital magnetic resonance imaging revealed an intraocular
      mass lesion; simultaneouslyobtained bone marrow and cerebrospinal fluid samples
      showed no evidence of leukemic cells. Following local irradiation,and systemic
      and intrathecal chemotherapy the mass disappeared. Local irradiation, and
      systemic and intrathecalchemotherapy effectively controlled the isolated ocular
      relapse of acute lymphoblastic leukemia and eliminated the needfor enucleation. 

PMID- 24744653
TI  - A Novel Homozygous Nucleotide Deletion in the JAK2 Gene in a Pediatric Patient
      with B-cell Precursor Acute Lymphoblastic Leukemia.

PMID- 24744654
TI  - The relationship between seasonal variation in the diagnosis of acute
      lymphoblastic leukemia and its prognosis in children.

PMID- 24744655
TI  - Successful treatment of refractory diamond-blackfan anemia using metoclopramide
      and prednisolone.

PMID- 24744656
TI  - Percutaneous vertebroplasty for osteoporotic vertebral fracture in a patient with
      sickle cell disease.

PMID- 24744657
TI  - Carbamazepine-induced Red Blood Cell Aplasia: A Case Report.

PMID- 24744658
TI  - Postpartum Acquired Hemophilia Factor VIII Inhibitors and Response to Therapy.

PMID- 24744659
TI  - Successful Treatment of Autoimmune Hemolytic Anemia with Steroid, IVIg, and
      Plasmapheresis in a Haploidentical Transplant Recipient.

PMID- 24744660
TI  - An extremely rare cause of bruising in children: autoerythrocyte sensitization
      syndrome.

PMID- 24744661
TI  - First Observation of MTH FR 678 C-A (Ala222Ala) Single Nucleotide Polymorphism.

PMID- 24744662
TI  - Myeloma Cells with Auer Rod-like Inclusions.

PMID- 24744664
TI  - Pulmonary radiological findings in patients with acute myeloid leukemia and their
      relationship to chemotherapy and prognosis: a single-center retrospective study.
AB  - OBJECTIVE: Acute myeloid leukemia (AML) is the most common acute leukemia in
      adults. Pulmonary are among the most common causes of mortality in AML. This
      single-center retrospective study aimed to evaluate the relationship between
      radiological findings of pulmonary at presentation and post chemotherapy on
      prognosis and clinical outcome in a group of AML patients. MATERIAL AND METHODS:
      The study included 278 AML patients. Clinical and radiological findings,
      laboratory findings, and microbiological culture results were evaluated.
      Pulmonary complications at presentation and post chemotherapy were compared.
      RESULTS: Pulmonary complications were observed in 53 of the patients (19%). Mean
      age of the patients with and without pulmonary complications was 43.1 +/- 15.2
      years and 38.8 +/- 16.3 years, respectively (P < 0.001). Pulmonary complications
      were not correlated with gender, AML subtype, or the serum lactate dehydrogenase
      (LDH) level. The most common cause of pulmonary complications was infection.
      Pulmonary complications were observed in 29% and 71% of the patients at
      presentation and post chemotherapy, respectively. CONCLUSION: Pulmonary
      complications were observed more frequently at presentation in neutropenic AML
      patients of advanced age. The mortality rate was higher among the AML patients
      that had pulmonary complications at presentation.

PMID- 24744663
TI  - Fertility-preserving treatment options in patients with malignant hematological
      diseases.
AB  - The number of patients of reproductive age diagnosed with various malignant
      hematological diseases increases every year. These patients undergo chemotherapy,
      radiotherapy, and various other treatments that may have gonadotoxic effects. The
      life expectancy of these patients is increasing rapidly due to the variety of
      treatment options. As such, an increasing number of patients-as well as their
      parents and spouses-express their concerns about the patient's fertility post
      treatment. In the present review it was aimed to provide an overview of current
      fertility-preserving treatment options and the future of fertility preservation. 

PMID- 24744665
TI  - Analysis of Chromosomal Aberrations and FLT3 gene Mutations in Childhood Acute
      Myelogenous Leukemia Patients.
AB  - OBJECTIVE: To identify the well-known common translocations and FLT3 mutations in
      childhood acute myelogenousleukemia (AML) patients in Turkey. MATERIAL AND
      METHODS: The study included 50 newly diagnosed patients in which t(15;17),
      t(8;21), and inv(16)chromosomal translocations were identified using real-time
      PCR and FLT3 gene mutations were identified via direct PCR amplification PCR-RE
      analysis. RESULTS: In all, t(15;17) chromosomal aberrations were observed in 4
      patients (8.0%), t(8;21) chromosomal aberrationswere observed in 12 patients
      (24.0%), inv(16) chromosomal aberrations were observed in 3 patients (6.0%), and
      FLT3-ITD mutations were observed in 2 patients (4.0%); FLT3-D835 point mutation
      heterozygosity was observed in only 1patient (2.0%) patient. CONCLUSION: Despite
      of the known literature, a patient with FLT3-ITD and FLT3-D835 double mutation
      shows a bettersurvival and this might be due to the complementation effect of the
      t(15;17) translocation. The reportedmutation ratein this article (4%) of FLT3
      gene seems to be one of the first results for Turkish population.

PMID- 24744666
TI  - Comparison of stored umbilical cord blood and adult donor blood: transfusion
      feasibility.
AB  - OBJECTIVE: This study aimed to compare the storage properties of red blood cell
      (RBC) concentrates of umbilical cordblood (UCB) and adult donor blood (ADB), and
      to evaluate the feasibility of UCB-RBC concentrate as an autologoussource for
      blood transfusion in very low birth weight (VLBW) preterm neonates. MATERIAL AND
      METHODS: In all, 30 newborn (10 preterm, 20 full term) UCB and 31 ADB units were
      collected.RBC concentrates were stored and compared with regard to pH, potassium
      (K(+)), 2,3-biphosphoglycerate (2-3-BPG),adenosine tri-phosphate (ATP), plasma
      Hb, and bacterial contamination on d 1, 21, and 35 of storage. RESULTS: The K(+)
      level increased with time and differed significantly between storage d 1 and 21,
      and between storaged 1 and 35 in both the UCB and ADB units. Initial and d 21
      K(+) levels were higher in the UCB units than in the ADBunits. The 2,3-BPG level
      did not differ significantly between the UCB-PRC and ADB-PRC samples. After 35 d
      of storageboth UCB-PRC and ADB-PRC samples exhibited significant differences from
      the initial free Hb, intracellular ATP, andpH values. Significant differences in
      intracellular ATP and pH were also observed between the UCB-PRC and ADB
      PRCsamples. CONCLUSION: The volume of harvested and prepared UCB-PRC can be used
      for some of the blood transfusions requiredduring the neonatal period and thus
      may decrease the number of allogeneic transfusions, especially in preterm
      newborns.The hematological and biochemical changes that occurred in UCB during
      storage were comparable with those observedin ADB, and do not pose a risk to the
      immature metabolism of neonates. UCB-RPC prepared and stored under
      standardconditions can be a safe alternative RBC source for transfusions in VLBW
      newborns.

PMID- 24744667
TI  - The Association Between JAK2V617F Mutation and Bone Marrow Fibrosis at Diagnosis
      in Patients with Philadelphia-Negative Chronic Myeloproliferative Neoplasms.
AB  - OBJECTIVE: Bone marrow fibrosis is the second most common complication that
      causes morbidity and mortality inpatients with Philadelphia-negative
      myeloproliferative neoplasms (MPNs). The aim of this study was to investigate
      theassociation between JAK2V617F mutation and bone marrow fibrosis at diagnosis
      in patients with MPNs. MATERIAL AND METHODS: In total, 149 patients with MPNs
      were retrospectively evaluated to determine if there was anassociation between
      the histological grade of bone marrow fibrosis and JAK2V617F mutation. RESULTS:
      In all, 67.7% of the patients carried the mutated JAK2 gene. The presence of
      JAK2V617F mutation was notassociated with the occurrence of bone marrow fibrosis
      (P=0.55) or its grade at diagnosis (P=0.65). CONCLUSION: Molecular mechanisms or
      genetic defects other than JAK2V617F may underlie the occurrence of bonemarrow
      fibrosis in patients with MPNs.

PMID- 24744668
TI  - Does reactive thrombocytosis observed in iron deficiency anemia affect plasma
      viscosity?
AB  - OBJECTIVE: The accompanying thrombocytosis is referred to as the major factor
      associated with thromboembolism in iron deficiency anemia (IDA). Increased
      viscosity may increase the risk of thrombosis. We hypothesized that increased
      platelet count -with reactive thrombocytosis- might also affect plasma viscosity.
      We planned to evaluate the influence of normal and high platelet count on plasma
      viscosity in IDA patients. MATERIAL AND METHODS: The patient population consisted
      of fifty-three newly diagnosed and untreated women aged between 18 and 62 years
      with IDA. Group 1 consisted of 33 patients, platelet levels below 400 x 10(9)/L.
      Group 2 consisted of 20 patients, platelet levels above 400 x 10(9)/L.
      Measurements of plasma viscosity were performed using Brookfield viscometer.
      RESULTS: Mean plasma viscosity was found as 1.05 +/- 0.08 mPa.s. in Group 1, and
      1.03 +/- 0.06 mPa.s. in Group 2. Mean plasma viscosity was not statistically
      different. White blood cell count was significantly higher in Group 2. Vitamin
      B12 levels were significantly higher in Group 2, while folic acid levels were
      higher in Group 1 (p=0.011 and p=0.033). Plasma viscosity was correlated with
      erythrocyte sedimentation rate (r=0.512 p=0.002) in Group 1 and inversely
      correlated with vitamin B12 (r=-0.480 p=0.032) in Group 2. CONCLUSION: Despite
      the significant difference between groups in terms of platelet count, no
      significant difference was detected in plasma viscosity and this finding could be
      explained as the following; 1-These platelets were not thrombocythemic platelets;
      2-Similar to the theory about leukocytes, higher platelet counts - even non
      thrombocythemic - may increase plasma viscosity; 3-Evaluating platelet count
      alone is not sufficient and the associating red-cell deformability should also be
      taken into account; and 4-Although other diseases that could affect viscosity are
      excluded, some definitely proven literature criteria such as fibrinogen,
      hyperlipidemia, and the inflammatory process should also be evaluated by
      laboratory and clinical measures.

PMID- 24744669
TI  - Secondary infections in cancer patients with febrile neutropenia.
AB  - OBJECTIVE: Patients with neutropenia due to cancer chemotherapy are prone to
      severe infections. Cancer patients canexperience >1 infectious episode during the
      same period of neutropenia. This study aimed to determine the etiologicaland
      clinical characteristics of secondary infectious episodes in cancer patients with
      febrile neutropenia and to identifythe factors associated with the risk of
      secondary infectious episodes. MATERIAL AND METHODS: All cancer patients that
      received antineoplastic chemotherapy at Ankara University, School ofMedicine,
      Department of Hematology between May 2004 and May 2005 and developed neutropenia
      were included in thestudy. Data were collected using survey forms that were
      completed during routine infectious diseases consultation visits.Categorical data
      were analyzed using the chi-square test, whereas Student's t-test was used for
      continuous variables.Multivariate logistic regression analysis was performed to
      identify independent predictors of secondary infections (SIs). RESULTS: SIs were
      observed during 138 (53%) of 259 febrile neutropenic episodes. Of the 138
      episodes, 89 (64.5%)occurred in male patients with a mean age of 40.9 years
      (range: 17-76 years). In total, 80% of the SIs were clinically
      ormicrobiologically documented. Factors on d 4 of the initial febrile episode
      were analyzed via a logistic regression model. The presence of a central
      intravenous catheter (OR: 3.01; P<0.001), acute myeloid leukemia (AML) as the
      underlyingdisease (OR: 2.12; P=0.008), diarrhea (OR: 4.59; P=0.005), and invasive
      aspergillosis (IA) during the initial febrileepisode (OR: 3.96; P=0.009) were
      statistically significant risk factors for SIs. CONCLUSION: Among the cancer
      patients with neutropenia in the present study, AML as the underlying disease,
      thepresence of a central venous catheter, diarrhea, and IA during the initial
      febrile episode were risk factors for thedevelopment of SIs.

PMID- 24744670
TI  - Psychiatric problems in children and adolescents with sickle cell disease, based
      on parent and teacher reports.
AB  - OBJECTIVE: This study aimed to investigate the occurrence of psychiatric problems
      in children and adolescents withsickle cell disease (SCD). MATERIAL AND METHODS:
      The Child Behavior Checklist for ages 4-18 years (CBCL/4-18), Conners' Parent
      RatingScale (CPRS), Conners' Teacher Rating Scale (CTRS-R), and The Turgay DSM-IV
      Based Child and Adolescent BehaviorDisorders Screening and Rating Scale,
      clinician and parent forms (T-DSM-IV-S) were given to the caregivers and
      teachersof 31 children with SCD aged between 7-18 years and the caregivers and
      teachers of 34 age matched controls with irondeficiencyanemia. RESULTS: The SCD
      patients had higher scores on all 4 of scales. Among the subscales, internalizing
      problems, andattention problems were more prominent in the SCD patients.
      CONCLUSION: Children and adolescents with SCD appear to have an increased risk
      for psychiatric problems. Regularpsychological evaluation and referral to child
      and adolescent psychiatry clinics may facilitate timely diagnosis andeffective
      treatment of at-risk children and adolescents.

PMID- 24744671
TI  - Familial Hemophagocytic Lymphohistiocytosis with A665G Perforin Gene Mutation: A
      Case Report.
AB  - Familial hemophagocytic lymphohistiocytosis (FHL) is a genetically heterogeneous
      disease. Presentation of the disease such as primarily fever, hepatosplenomegaly,
      and cytopenia, which are the results of functional degradation in cytotoxic T
      lymphocytes and natural killer cells, activation of macrophages and T
      lymphocytes, over production of proinflammatory cytokines, and hemophagocytosis.
      In all, 5 genetic loci have been identified in FHL, and all known affected genes
      encode critical components of the granule exocytosis pathway, which is essential
      for the release of cytotoxic granules and proteases that are necessary for
      targeted cell death. Herein we present an FHL patient with a severe clinical
      course and a very rare perforin gene mutation. The patient was homozygous for
      A665G mutation. However, the child died in a short period of time. Prenatal
      diagnosis was performed in the family and the fetus was found to be heterozygous
      for the mutation. 

PMID- 24744672
TI  - Treatment of Priapism with Automated Red Cell Exchange and Hyperbaric Oxygen in
      an 11-year-old Patient with Sickle Cell Disease.
AB  - Priapism affects up to 50% of all males with sickle cell disease, and there is no
      standard treatment. Delayed and unsuccessful treatment leads to corporal fibrosis
      and impotence. It is therefore necessary to determine the best treatment methods
      for this complication in order to offer effective interventions to all affected
      patients. Herein we report an 11-year-old patient with sickle cell disease that
      presented with priapism 72 h after onset, and was successfully treated with
      automated red cell exchange and hyperbaric oxygen following unsuccessful surgical
      and conventional interventions. 

PMID- 24744673
TI  - Primary Breast Mucosa-Associated Lymphoid Tissue (MALT) Lymphoma Transformation
      to Diffuse Large B-cell Lymphoma: A Case Report.
AB  - Primary non-Hodgkin's lymphoma (NHL) of the breast constitutes 0.04%-0.53% of all
      malignancies and 2.2% of extra nodal lymphomas. In total, 7%-8% of all B-cell
      lymphomas are the mucosa-associated lymphoid tissue (MALT) type, of which up to
      50% of primary gastric MALT lymphoma. Herein we present a patient with breast
      MALT lymphoma that transformed to diffuse large B-cell lymphoma (DLBCL). A 69
      year-old female presented with a mass on her left breast. Physical examination
      showed a 3*3-cm mass located 1 cm from the areola on the upper lateral quadrant
      of the breast at the 1 o'clock position, which was fixed and firm. Excisional
      biopsy was performed and pathologic examination of the specimen showed MALT
      lymphoma transformation to DLBCL. The patient was staged as II-EA. The rituximab,
      cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP) protocol
      was scheduled as treatment. Following 6 courses of R-CHOP, 2 additional courses
      of rituximab were administered. Positron emission tomography (PET)-CT was done at
      the end of the treatment. PET showed that the patient was in complete remission.
      At the time this report was written, the patient was being followed-up at the
      outpatient clinic on a regular basis. Lymphoma of the breast is a rarity among
      malignant tumors of the breast. The most common type of lymphoma is DLBCL. Breast
      MALT lymphoma is extremely rare. Primary MALT lymphoma of the breast can
      transform from low grade to high grade and recurrence is possible; therefore,
      such patients should be monitored carefully for transformation. 

PMID- 24744674
TI  - Myeloid sarcoma: an unusual presentation of acute promyelocytic leukemia causing
      spinal cord compression.
AB  - Acute promyelocytic leukemia with concurrent myeloid sarcoma is a rare clinical
      event. Herein we describe a patient that presented with back pain and bilateral
      leg weakness caused by spinal cord compression due to extramedullary deposition
      of leukemic cells. Acute promyelocytic leukemia was suspected based on
      immunophenotypic findings of malignant cells in bone marrow aspirate. The
      diagnosis was confirmed by the presence of PML-RARalpha fusion copies. MRI showed
      multiple hyperintense changes on the vertebral bodies, together with intraspinal
      masses causing spinal cord compression. The patient immediately underwent
      radiotherapy, and was treated with all-trans retinoic acid and idarubicin.
      Reassessment MRI showed complete resolution of all intraspinal masses and the
      disappearance of most of the bony lesions. Post-treatment bone marrow aspirate
      showed complete hematological and molecular remission. The motor power of his
      legs fully recovered from 0/5 to 5/5; however, sensory loss below the T4 level
      persisted. 

PMID- 24744675
TI  - First observation of hemoglobin m saskatoon (beta63 (e7) his>tyr(c-t)) in the
      iraqi population.

PMID- 24744676
TI  - HbA2-Yokoshima (delta 25(B7)Gly >Asp) and Hb A2-Yialousa (delta 27(B9)Ala>Ser) in
      Turkey.

PMID- 24744677
TI  - Spontaneous subdural hematoma associated with kasabach-merritt syndrome: a case
      report.

PMID- 24744678
TI  - Inverse tone mapping based upon retina response.
AB  - The development of high dynamic range (HDR) display arouses the research of
      inverse tone mapping methods, which expand dynamic range of the low dynamic range
      (LDR) image to match that of HDR monitor. This paper proposed a novel
      physiological approach, which could avoid artifacts occurred in most existing
      algorithms. Inspired by the property of the human visual system (HVS), this
      dynamic range expansion scheme performs with a low computational complexity and a
      limited number of parameters and obtains high-quality HDR results. Comparisons
      with three recent algorithms in the literature also show that the proposed method
      reveals more important image details and produces less contrast loss and
      distortion. 

PMID- 24744679
TI  - Improved delay-dependent stability conditions for MIMO networked control systems
      with nonlinear perturbations.
AB  - This paper provides improved time delay-dependent stability criteria for multi
      input and multi-output (MIMO) network control systems (NCSs) with nonlinear
      perturbations. Without the stability assumption on the neutral operator after the
      descriptor approach, the new proposed stability theory is less conservative than
      the existing stability condition. Theoretical proof is given in this paper to
      demonstrate the effectiveness of the proposed stability condition. 

PMID- 24744680
TI  - A parallel algorithm for the two-dimensional time fractional diffusion equation
      with implicit difference method.
AB  - It is very time consuming to solve fractional differential equations. The
      computational complexity of two-dimensional fractional differential equation (2D
      TFDE) with iterative implicit finite difference method is O(M(x)M(y)N(2)). In
      this paper, we present a parallel algorithm for 2D-TFDE and give an in-depth
      discussion about this algorithm. A task distribution model and data layout with
      virtual boundary are designed for this parallel algorithm. The experimental
      results show that the parallel algorithm compares well with the exact solution.
      The parallel algorithm on single Intel Xeon X5540 CPU runs 3.16-4.17 times faster
      than the serial algorithm on single CPU core. The parallel efficiency of 81
      processes is up to 88.24% compared with 9 processes on a distributed memory
      cluster system. We do think that the parallel computing technology will become a
      very basic method for the computational intensive fractional applications in the
      near future.

PMID- 24744681
TI  - Expression of interleukin-17A in lung tissues of irradiated mice and the
      influence of dexamethasone.
AB  - PURPOSE: To investigate the expressions of IL-17A in different phases of
      radiation-induced lung injury and the effect of dexamethasone. METHODS: The
      thorax of C57BL/6 mice was irradiated with 15 Gy rays. Mice from dexamethasone
      treated group were injected intraperitoneally with dexamethasone (0.42 mg/kg/day)
      every day for the first month after irradiation. IL-17A in lung tissues was
      detected by immunohistochemistry. IL-17A, TGF-beta1, and IL-6 in bronchoalveolar
      lavage fluid were detected by ELISA. Lung inflammation and collagen deposition
      were observed by H&E and Masson methods. The degree of alveolitis and fibrosis
      was judged according to scoring. RESULTS: IL-17A expression was appreciable at 1
      week, peaked at 4 weeks, and subsequently declined at 8 weeks after irradiation.
      IL-17A was reduced after dexamethasone application at all the observation
      periods. Dexamethasone also inhibited expressions of TGF-beta, IL-6, and TNF
      alpha in bronchoalveolar lavage fluid. Moreover, dexamethasone attenuated the
      severity of lung injury by reducing the infiltration of inflammatory cells and
      collagen deposition. Terms of survival and the time of death in mice of treatment
      group were postponed and survival rate was improved. CONCLUSIONS: IL-17A plays an
      important role in the process of radiation-induced lung injury. And dexamethasone
      may provide a protective role in lung injury induced by radiation.

PMID- 24744683
TI  - WDM network and multicasting protocol strategies.
AB  - Optical technology gains extensive attention and ever increasing improvement
      because of the huge amount of network traffic caused by the growing number of
      internet users and their rising demands. However, with wavelength division
      multiplexing (WDM), it is easier to take the advantage of optical networks and
      optical burst switching (OBS) and to construct WDM networks with low delay rates
      and better data transparency these technologies are the best choices.
      Furthermore, multicasting in WDM is an urgent solution for bandwidth-intensive
      applications. In the paper, a new multicasting protocol with OBS is proposed. The
      protocol depends on a leaf initiated structure. The network is composed of
      source, ingress switches, intermediate switches, edge switches, and client nodes.
      The performance of the protocol is examined with Just Enough Time (JET) and Just
      In Time (JIT) reservation protocols. Also, the paper involves most of the recent
      advances about WDM multicasting in optical networks. WDM multicasting in optical
      networks is given as three common subtitles: Broadcast and-select networks,
      wavelength-routed networks, and OBS networks. Also, in the paper, multicast
      routing protocols are briefly summarized and optical burst switched WDM networks
      are investigated with the proposed multicast schemes. 

PMID- 24744682
TI  - The neurobiological pathogenesis of poststroke depression.
AB  - Poststroke depression (PSD) is an important consequence after stroke, with
      negative impact on stroke outcome. The pathogenesis of PSD is complicated, with
      some special neurobiological mechanism, which mainly involves neuroanatomical,
      neuron, and biochemical factors and neurogenesis which interact in complex ways.
      Abundant studies suggested that large lesions in critical areas such as left
      frontal lobe and basal ganglia or accumulation of silent cerebral lesions might
      interrupt the pathways of monoamines or relevant pathways of mood control, thus
      leading to depression. Activation of immune system after stroke produces more
      cytokines which increase glutamate excitotoxicity, results in more cell deaths of
      critical areas and enlargement of infarctions, and, together with
      hypercortisolism induced by stress or inflammation after stroke which could
      decrease intracellular serotonin transporters, might be the key biochemical
      change of PSD. The interaction among cytokines, glucocorticoid, and neurotrophin
      results in the decrease of hippocampal neurogenesis which has been proved to be
      important for mood control and pharmaceutical effect of selective serotonin
      reuptake inhibitors and might be another promising pathway to understand the
      pathogenesis of PSD. In order to reduce the prevalence of PSD and improve the
      outcome of stroke, more relevant studies are still required to clarify the
      pathogenesis of PSD. 

PMID- 24744684
TI  - An improved quantitative analysis method for plant cortical microtubules.
AB  - The arrangement of plant cortical microtubules can reflect the physiological
      state of cells. However, little attention has been paid to the image quantitative
      analysis of plant cortical microtubules so far. In this paper, Bidimensional
      Empirical Mode Decomposition (BEMD) algorithm was applied in the image
      preprocessing of the original microtubule image. And then Intrinsic Mode Function
      1 (IMF1) image obtained by decomposition was selected to do the texture analysis
      based on Grey-Level Cooccurrence Matrix (GLCM) algorithm. Meanwhile, in order to
      further verify its reliability, the proposed texture analysis method was utilized
      to distinguish different images of Arabidopsis microtubules. The results showed
      that the effect of BEMD algorithm on edge preserving accompanied with noise
      reduction was positive, and the geometrical characteristic of the texture was
      obvious. Four texture parameters extracted by GLCM perfectly reflected the
      different arrangements between the two images of cortical microtubules. In
      summary, the results indicate that this method is feasible and effective for the
      image quantitative analysis of plant cortical microtubules. It not only provides
      a new quantitative approach for the comprehensive study of the role played by
      microtubules in cell life activities but also supplies references for other
      similar studies. 

PMID- 24744685
TI  - Interaction prediction optimization in multidisciplinary design optimization
      problems.
AB  - The distributed strategy of Collaborative Optimization (CO) is suitable for large
      scale engineering systems. However, it is hard for CO to converge when there is a
      high level coupled dimension. Furthermore, the discipline objectives cannot be
      considered in each discipline optimization problem. In this paper, one large
      scale systems control strategy, the interaction prediction method (IPM), is
      introduced to enhance CO. IPM is utilized for controlling subsystems and
      coordinating the produce process in large-scale systems originally. We combine
      the strategy of IPM with CO and propose the Interaction Prediction Optimization
      (IPO) method to solve MDO problems. As a hierarchical strategy, there are a
      system level and a subsystem level in IPO. The interaction design variables
      (including shared design variables and linking design variables) are operated at
      the system level and assigned to the subsystem level as design parameters. Each
      discipline objective is considered and optimized at the subsystem level
      simultaneously. The values of design variables are transported between system
      level and subsystem level. The compatibility constraints are replaced with the
      enhanced compatibility constraints to reduce the dimension of design variables in
      compatibility constraints. Two examples are presented to show the potential
      application of IPO for MDO. 

PMID- 24744686
TI  - Assessment of density variations of marine sediments with ocean and sediment
      depths.
AB  - We analyze the density distribution of marine sediments using density samples
      taken from 716 drill sites of the Deep Sea Drilling Project (DSDP). The samples
      taken within the upper stratigraphic layer exhibit a prevailing trend of the
      decreasing density with the increasing ocean depth (at a rate of -0.05 g/cm(3)
      per 1 km). Our results confirm findings of published studies that the density
      nonlinearly increases with the increasing sediment depth due to compaction. We
      further establish a 3D density model of marine sediments and propose theoretical
      models of the ocean-sediment and sediment-bedrock density contrasts. The sediment
      density-depth equation approximates density samples with an average uncertainty
      of about 10% and better represents the density distribution especially at deeper
      sections of basin sediments than a uniform density model. The analysis of DSDP
      density data also reveals that the average density of marine sediments is 1.70
      g/cm(3) and the average density of the ocean bedrock is 2.9 g/cm(3).

PMID- 24744687
TI  - A preliminary study of the algicidal mechanism of bioactive metabolites of
      Brevibacillus laterosporus on Oscillatoria in prawn ponds.
AB  - The algae, Oscillatoria, is commonly found in prawn ponds and can lead to reduced
      productivity. We examined metabolites of the bacteria Brevibacillus laterosporus
      for algicidal qualities. To determine the possible algicidal mechanisms of these
      bioactive metabolites, different amounts of sterile filtrate of bacterial
      suspensions were added to cultures containing Oscillatoria. The dry weight, the
      concentrations of chlorophyll-a (chl-a), phycobiliprotein (PC, phycocyanin; APC,
      allophycocyanin; PE, phycoerythrin), and MDA (malondialdehyde) and the activities
      of SOD (superoxide dismutase), POD (peroxidase), and CAT (catalase) of algae were
      measured during the algicidal application. The results showed that lower
      concentrations of the sterile filtrate (addition <= 4 mL) accelerated the growth
      rate of Oscillatoria, but significant inhibition and lysis were observed with
      higher concentrations (addition >= 8 mL). In two trials (the additions were 8 mL
      and 10 mL, respectively), the algal dry weights were reduced by 26.02% and
      45.30%, and the chl-a concentrations were decreased by 46.88% and 63.73%,
      respectively, after seven days. During the algicidal treatment, the
      concentrations of PC, APC, PE, and MDA and the activities of SOD, POD, and CAT
      were significantly increased in the early cultivation and declined quickly at
      later stages. Finally, the algae-lysing mechanism of the bioactive metabolites of
      the bacteria Brevibacillus laterosporus on Oscillatoria had been proposed.

PMID- 24744688
TI  - Stress-strain behavior of cementitious materials with different sizes.
AB  - The size dependence of flexural properties of cement mortar and concrete beams is
      investigated. Bazant's size effect law and modified size effect law by Kim and Eo
      give a very good fit to the flexural strength of both cement mortar and concrete.
      As observed in the test results, a strong size effect in flexural strength is
      found in cement mortar than in concrete. A modification has been suggested to
      Li's equation for describing the stress-strain curve of cement mortar and
      concrete by incorporating two different correction factors, the factors contained
      in the modified equation being established empirically as a function of specimen
      size. A comparison of the predictions of this equation with test data generated
      in this study shows good agreement. 

PMID- 24744689
TI  - Site-specific analysis of inflammatory markers in discoid lupus erythematosus
      skin.
AB  - Prior studies identified T cells, B cells, and macrophages in the inflammatory
      infiltrate and up-regulation of their protein products in discoid lupus
      erythematosus (DLE) skin; however, they lacked rigorous analyses to define their
      specific locations in skin. Thus, we compared expressions of selected T cell, B
      cell, and macrophage markers in five areas of DLE, psoriasis, and normal skin.
      Immunostainings for CD3, CD4, CD8, CD20, CD68, CXCR3, CXCL10, and TIA-1 were
      performed in biopsies of 23 DLE lesional skin, 11 psoriasis lesional skin, and 5
      normal skin. Three independent observers used a graded scale to rate each
      marker's presence in the epidermis, dermatoepidermal junction (DEJ), perivascular
      area, periadnexal area, and deep dermis. DLE lesional skin contained an increased
      abundance of CD3(+), CD8(+), and CD68(+) cells at the DEJ, and CD20(+) and
      CD68(+) cells in the periadnexal area versus psoriasis and normal skin. CXCR3,
      CXCL10, and TIA-1 were elevated in periadnexal sites of DLE lesional skin versus
      psoriasis lesional skin. The aggregation of T cells, B cells, macrophages, and
      their protein products (CXCR3, CXCL10, and TIA-1) in the DEJ and periadnexal area
      of DLE lesional skin may contribute to the pathology of DLE through a
      coordinated, sophisticated process. 

PMID- 24744690
TI  - Dissolved concentrations, sources, and risk evaluation of selected metals in
      surface water from Mangla Lake, Pakistan.
AB  - The present study is carried out for the assessment of water quality parameters
      and selected metals levels in surface water from Mangla Lake, Pakistan. The metal
      levels (Ca, Cd, Co, Cr, Cu, Fe, K, Li, Mg, Mn, Na, Ni, Pb, Sr, and Zn) were
      determined by flame atomic absorption spectrophotometry. Average levels of Cd,
      Co, Cr, Ni, and Pb were higher than the allowable concentrations set by national
      and international agencies. Principal component analysis indicated significant
      anthropogenic contributions of Cd, Co, Cr, Ni, and Pb in the water reservoir.
      Noncarcinogenic risk assessment was then evaluated using Hazard Quotient
      (HQ(ing/derm)) and Hazard Index (HI(ing/derm)) following USEPA methodology. For
      adults and children, Cd, Co, Cr, and Pb (HQ(ing) > 1) emerged as the most
      important pollutants leading to noncarcinogenic concerns via ingestion route,
      whereas there was no risk via dermal contact of surface water. This study helps
      in establishing pollutant loading reduction goal and the total maximum daily
      loads, and consequently contributes to preserve public health and develop water
      conservation strategy.

PMID- 24744691
TI  - Evaluation of DNA Binding, Cleavage, and Cytotoxic Activity of Cu(II), Co(II),
      and Ni(II) Schiff Base Complexes of 1-Phenylindoline-2,3-dione with
      Isonicotinohydrazide.
AB  - One new series of Cu(II), Co(II), and Ni(II) Schiff base complexes was prepared
      through the condensation reaction between 1-phenylindoline-2,3-dione with
      isonicotinohydrazide followed by metalation, respectively. The Schiff base
      ligand(L), (E)-N'-(2-oxo-1-phenylindolin-3-lidene)isonicotinohydrazide, and its
      complexes were found soluble in DMF and DMSO solvents and characterized by using
      the modern analytical and spectral techniques such as elemental analysis,
      conductivity, magnetic moments, IR, NMR, UV-visible, Mass, CV, and EPR. The
      elemental analysis data of ligand and their complexes were well agreed with their
      calculated values in which metal and ligand stoichiometry ratio 1 : 2 was noted.
      Molar conductance values indicated that all the complexes were found to be
      nonelectrolytes. All the complexes showed octahedral geometry around the central
      metal ions. Herein, we better characterized DNA binding with the complexes by UV
      visible and CD spectroscopy and cyclic voltammetry techniques. The DNA cleavage
      experiments were carried out by Agarose gel electrophoresis method and the
      cytotoxicity experiments by MTT assay method. Based on the DNA binding, cleavage,
      and cytotoxicity studies, Cu and Ni complexes were found to be good anticancer
      agents against AGS-human gastric cancer cell line. 

PMID- 24744692
TI  - Synthesis and Spectroscopic and Biological Activities of Zn(II) Porphyrin with
      Oxygen Donors.
AB  - Results of investigation of the physicochemical properties of zinc complexes
      containing substituted phenols as axial ligand having general formula [X-Zn-t(p
      CH3) PP] [where X = different phenolates as axial ligand] in impurity-free
      organic solvent are presented. The four-coordinated zinc porphyrin accepts one
      axial ligand in 1 : 1 molar ratio to form five-coordinated complex, which is
      purified by column chromatography and characterized by physicochemical,
      biological evaluation and TGA/DTA studies. Absorption spectra show two principal
      effects: a red shift for phenols bearing substituted electron releasing groups (
      CH3, -NH2) and blue shift for phenols bearing electron withdrawing groups (-NO2, 
      Cl) relative to Zn-t(p-CH3) PP, respectively. (1)H NMR spectra show that the
      protons of the phenol ring axially attached to the central metal ion are merged
      with the protons of the porphyrin ring. Fluorescence spectra show two
      fluorescence peaks in the red region with emission ranging from 550 nm to 700 nm.
      IR spectra confirm the appearance of Zn-NPor and Zn-O vibrational frequencies,
      respectively. According to the thermal studies, the complexes have a higher
      thermal stability and the decomposition temperature of these complexes depends on
      the axial ligation. The respective complexes of X-Zn(II)-t(p-CH3) PP were found
      to possess higher antifungal activity (up to 90%) and higher in vitro
      cytotoxicity against human cancer cells lines. 

PMID- 24744694
TI  - On the use of orientation filters for 3D reconstruction in event-driven stereo
      vision.
AB  - The recently developed Dynamic Vision Sensors (DVS) sense visual information
      asynchronously and code it into trains of events with sub-micro second temporal
      resolution. This high temporal precision makes the output of these sensors
      especially suited for dynamic 3D visual reconstruction, by matching corresponding
      events generated by two different sensors in a stereo setup. This paper explores
      the use of Gabor filters to extract information about the orientation of the
      object edges that produce the events, therefore increasing the number of
      constraints applied to the matching algorithm. This strategy provides more
      reliably matched pairs of events, improving the final 3D reconstruction. 

PMID- 24744695
TI  - Predictability effects in auditory scene analysis: a review.
AB  - Many sound sources emit signals in a predictable manner. The idea that
      predictability can be exploited to support the segregation of one source's signal
      emissions from the overlapping signals of other sources has been expressed for a
      long time. Yet experimental evidence for a strong role of predictability within
      auditory scene analysis (ASA) has been scarce. Recently, there has been an
      upsurge in experimental and theoretical work on this topic resulting from
      fundamental changes in our perspective on how the brain extracts predictability
      from series of sensory events. Based on effortless predictive processing in the
      auditory system, it becomes more plausible that predictability would be available
      as a cue for sound source decomposition. In the present contribution, empirical
      evidence for such a role of predictability in ASA will be reviewed. It will be
      shown that predictability affects ASA both when it is present in the sound source
      of interest (perceptual foreground) and when it is present in other sound sources
      that the listener wishes to ignore (perceptual background). First evidence
      pointing toward age-related impairments in the latter capacity will be addressed.
      Moreover, it will be illustrated how effects of predictability can be shown by
      means of objective listening tests as well as by subjective report procedures,
      with the latter approach typically exploiting the multi-stable nature of auditory
      perception. Critical aspects of study design will be delineated to ensure that
      predictability effects can be unambiguously interpreted. Possible mechanisms for
      a functional role of predictability within ASA will be discussed, and an analogy
      with the old-plus-new heuristic for grouping simultaneous acoustic signals will
      be suggested. 

PMID- 24744696
TI  - Chronochemistry in neurodegeneration.
AB  - The problem of distinguishing causes from effects is not a trivial one, as
      illustrated by the science fiction writer Isaac Asimov in a novel dedicated to an
      imaginary compound with surprising "chronochemistry" properties. The problem is
      particularly important when trying to establish the etiology of diseases. Here,
      we discuss how the problem reflects on our understanding of disease using two
      specific examples: Alzheimer's disease (AD) and Friedreich's ataxia (FRDA). We
      show how the fibrillar aggregates observed in AD were first denied any interest,
      then to assume a central focus, and to finally recess to be considered the dead
      end point of the aggregation pathway. This current view is that the soluble
      aggregates formed along the aggregation pathway rather than the mature amyliod
      fiber are the causes of disease, Similarly, we illustrate how the identification
      of causes and and effects have been important in the study of FRDA. This disease
      has alternatively been considered as the consequence of oxidative stress, iron
      precipitation or reduction of iron-sulfur cluster protein context. We illustrate
      how new tools have recently been established which allow us to follow the
      development of the disease. We hope that this review may inspire similar studies
      in other scientific disciplines. 

PMID- 24744698
TI  - Sarm1 deficiency impairs synaptic function and leads to behavioral deficits,
      which can be ameliorated by an mGluR allosteric modulator.
AB  - Innate immune responses have been shown to influence brain development and
      function. Dysregulation of innate immunity is significantly associated with
      psychiatric disorders such as autism spectrum disorders and schizophrenia, which
      are well-known neurodevelopmental disorders. Recent studies have revealed that
      critical players of the innate immune response are expressed in neuronal tissues
      and regulate neuronal function and activity. For example, Sarm1, a negative
      regulator that acts downstream of Toll-like receptor (TLR) 3 and 4, is
      predominantly expressed in neurons. We have previously shown that Sarm1 regulates
      neuronal morphogenesis and the expression of inflammatory cytokines in the brain,
      which then affects learning ability, cognitive flexibility, and social
      interaction. Because impaired neuronal morphogenesis and dysregulation of
      cytokine expression may disrupt neuronal activity, we investigated whether Sarm1
      knockdown affects the synaptic responses of neurons. We here show that reduced
      Sarm1 expression impairs metabotropic glutamate receptor (mGluR)-dependent long
      term depression (LTD) formation but enhances N-methyl-D-aspartate receptor
      (NMDAR)-dependent long-term potentiation production in hippocampal CA1 neurons.
      The expression levels of post-synaptic proteins, including NR2a, NR1, Shank1 and
      Shank3, are also altered in Sarm1 knockdown mice, suggesting a role for Sarm1 in
      the maintenance of synaptic homeostasis. The addition of a positive allosteric
      modulator of mGluR5, CDPPB, ameliorates the LTD defects in slice recording and
      the behavioral deficits in social interaction and associative memory. These
      results suggest an important role for mGluR5 signaling in the function of Sarm1.
      In conclusion, our study demonstrates a role for Sarm1 in the regulation of
      synaptic plasticity. Through these mechanisms, Sarm1 knockdown results in the
      impairment of associative memory and social interactions in mice. 

PMID- 24744697
TI  - Subcellular targeting and dynamic regulation of PTEN: implications for neuronal
      cells and neurological disorders.
AB  - PTEN is a lipid and protein phosphatase that regulates a diverse range of
      cellular mechanisms. PTEN is mainly present in the cytosol and transiently
      associates with the plasma membrane to dephosphorylate PI(3,4,5)P3, thereby
      antagonizing the PI3-Kinase signaling pathway. Recently, PTEN has been shown to
      associate also with organelles such as the endoplasmic reticulum (ER), the
      mitochondria, or the nucleus, and to be secreted outside of the cell. In
      addition, PTEN dynamically localizes to specialized sub-cellular compartments
      such as the neuronal growth cone or dendritic spines. The diverse localizations
      of PTEN imply a tight temporal and spatial regulation, orchestrated by mechanisms
      such as posttranslational modifications, formation of distinct protein-protein
      interactions, or the activation/recruitment of PTEN downstream of external cues.
      The regulation of PTEN function is thus not only important at the enzymatic
      activity level, but is also associated to its spatial distribution. In this
      review we will summarize (i) recent findings that highlight mechanisms
      controlling PTEN movement and sub-cellular localization, and (ii) current
      understanding of how PTEN localization is achieved by mechanisms controlling
      posttranslational modification, by association with binding partners and by PTEN
      structural or activity requirements. Finally, we will discuss the possible roles
      of compartmentalized PTEN in developing and mature neurons in health and disease.

PMID- 24744699
TI  - Regulating amyloidogenesis through the natural triggering receptor expressed in
      myeloid/microglial cells 2 (TREM2).

PMID- 24744700
TI  - Why looking at the whole hippocampus is not enough-a critical role for
      anteroposterior axis, subfield and activation analyses to enhance predictive
      value of hippocampal changes for Alzheimer's disease diagnosis.
AB  - The hippocampus is one of the earliest affected brain regions in Alzheimer's
      disease (AD) and its dysfunction is believed to underlie the core feature of the
      disease-memory impairment. Given that hippocampal volume is one of the best AD
      biomarkers, our review focuses on distinct subfields within the hippocampus,
      pinpointing regions that might enhance the predictive value of current diagnostic
      methods. Our review presents how changes in hippocampal volume, shape, symmetry
      and activation are reflected by cognitive impairment and how they are linked with
      neurogenesis alterations. Moreover, we revisit the functional differentiation
      along the anteroposterior longitudinal axis of the hippocampus and discuss its
      relevance for AD diagnosis. Finally, we indicate that apart from hippocampal
      subfield volumetry, the characteristic pattern of hippocampal hyperactivation
      associated with seizures and neurogenesis changes is another promising candidate
      for an early AD biomarker that could become also a target for early
      interventions. 

PMID- 24744701
TI  - Tis21 is required for adult neurogenesis in the subventricular zone and for
      olfactory behavior regulating cyclins, BMP4, Hes1/5 and Ids.
AB  - Bone morphogenic proteins (BMPs) and the Notch pathway regulate quiescence and
      self-renewal of stem cells of the subventricular zone (SVZ), an adult neurogenic
      niche. Here we analyze the role at the intersection of these pathways of Tis21
      (Btg2/PC3), a gene regulating proliferation and differentiation of adult SVZ stem
      and progenitor cells. In Tis21-null SVZ and cultured neurospheres, we observed a
      strong decrease in the expression of BMP4 and its effectors Smad1/8, while the
      Notch anti-neural mediators Hes1/5 and the basic helix-loop-helix (bHLH)
      inhibitors Id1-3 increased. Consistently, expression of the proneural bHLH gene
      NeuroD1 decreased. Moreover, cyclins D1/2, A2, and E were strongly up-regulated.
      Thus, in the SVZ Tis21 activates the BMP pathway and inhibits the Notch pathway
      and the cell cycle. Correspondingly, the Tis21-null SVZ stem cells greatly
      increased; nonetheless, the proliferating neuroblasts diminished, whereas the
      post-mitotic neuroblasts paradoxically accumulated in SVZ, failing to migrate
      along the rostral migratory stream to the olfactory bulb. The ability, however,
      of neuroblasts to migrate from SVZ explants was not affected, suggesting that
      Tis21-null neuroblasts do not migrate to the olfactory bulb because of a defect
      in terminal differentiation. Notably, BMP4 addition or Id3 silencing rescued the
      defective differentiation observed in Tis21-null neurospheres, indicating that
      they mediate the Tis21 pro-differentiative action. The reduced number of granule
      neurons in the Tis21-null olfactory bulb led to a defect in olfactory detection
      threshold, without effect on olfactory memory, also suggesting that within
      olfactory circuits new granule neurons play a primary role in odor sensitivity
      rather than in memory. 

PMID- 24744702
TI  - Microglial diversity by responses and responders.
AB  - Microglia are the principal resident innate immune cells of the CNS. Their
      contributions to the normal development of the CNS, the maintenance and
      plasticity of neuronal networks and the safeguarding of proper functionality are
      becoming more and more evident. Microglia also survey the tissue homeostasis to
      respond rapidly to exogenous and endogenous threats, primarily with a protective
      outcome. However, excessive acute activation, chronic activity or an improper
      adaptation of their functional performance can foster neuropathologies. A key to
      the versatile response behavior of these cells is their ability to commit to
      reactive phenotypes, which reveal enormous complexity. Yet the respective
      profiles of induced genes and installed functions may build up on heterogeneous
      contributions of cellular subsets. Here, we discuss findings and concepts that
      consider the variety of microglial activities and response options as being based
      at least in part-on a diversity of the engaged cells. Whether it is the
      production of proinflammatory cytokines, clearance of tissue debris, antigen
      presentation or the ability to sense neurotransmitters, microglial cells present
      with an unanticipated heterogeneity of their constitutive and inducible features.
      While the organizational principles of this heterogeneity are still largely
      unknown, functional implications are already perceptible. 

PMID- 24744703
TI  - Distribution of GABAergic cells in the inferior colliculus that project to the
      thalamus.
AB  - A GABAergic component has been identified in the projection from the inferior
      colliculus (IC) to the medial geniculate body (MG) in cats and rats. We sought to
      determine if this GABAergic pathway exists in guinea pig, a species widely used
      in auditory research. The guinea pig IC contains GABAergic cells, but their
      relative abundance in the IC and their relative contributions to tectothalamic
      projections are unknown. We identified GABAergic cells with immunochemistry for
      glutamic acid decarboxylase (GAD) and determined that ~21% of IC neurons are
      GABAergic. We then combined retrograde tracing with GAD immunohistochemistry to
      identify the GABAergic tectothalamic projection. Large injections of Fast Blue,
      red fluorescent beads or FluoroGold were deposited to include all subdivisions of
      the MG. The results demonstrate a GABAergic pathway from each IC subdivision to
      the ipsilateral MG. GABAergic cells constitute ~22% of this ipsilateral pathway.
      In addition, each subdivision of the IC had a GABAergic projection to the
      contralateral MG. Measured by number of tectothalamic cells, the contralateral
      projection is about 10% of the size of the ipsilateral projection. GABAergic
      cells constitute about 20% of the contralateral projection. In summary, the
      results demonstrate a tectothalamic projection in guinea pigs that originates in
      part from GABAergic cells that project ipsilaterally or contralaterally to the
      MG. The results show similarities to both rats and cats, and carry implications
      for the role of GABAergic tectothalamic projections vis-a-vis the presence (in
      cats) or near absence (in rats and guinea pigs) of GABAergic interneurons in the
      MG. 

PMID- 24744704
TI  - Restricted expression of classic cadherins in the spinal cord of the chicken
      embryo.
AB  - Classic cadherins belong to the family of cadherin genes and play important roles
      in neurogenesis, neuron migration, and axon growth. In the present study, we
      compared the expression patterns of 10 classic cadherins (Cdh2, Cdh4, Cdh6, Cdh7,
      Cdh8, Cdh9, Cdh11, Cdh12, Cdh18, and Cdh20) in the developing chicken spinal cord
      (SP) by in situ hybridization. Our results indicate that each of the investigated
      cadherins exhibits a spatially restricted and temporally regulated pattern of
      expression. At early developmental stages (E2.5-E3), Cdh2 is expressed throughout
      the neuroepithelial layer. Cdh6 is strongly positive in the roof plate and later
      also in the floor plate. Cdh7, Cdh11, Cdh12, and Cdh20 are expressed in
      restricted regions of the basal plate of the SP. At intermediate stages of
      development (E4-E10), specific expression profiles are observed for all
      investigated cadherins in the differentiating mantle layer along the
      dorsoventral, mediolateral, and rostrocaudal dimensions. Expression profiles are
      especially diverse for Cdh2, Cdh4, Cdh8, Cdh11, and Cdh20 in the dorsal horn,
      while different pools of motor neurons exhibit signal for Cdh6, Cdh7, Cdh8, Cdh9,
      Cdh12, and Cdh20 in the ventral horn. Interestingly, subpopulations of cells in
      the dorsal root ganglion express combinations of different cadherins. In the
      surrounding tissues, such as the boundary cap cells and the notochord, the
      cadherins are also expressed differentially. The highly regulated spatiotemporal
      expression patterns of the classic cadherins indicate that these genes
      potentially play multiple and diverse roles during the development of the SP and
      its surrounding tissues. 

PMID- 24744705
TI  - Time of day influences memory formation and dCREB2 proteins in Drosophila.
AB  - Many biological phenomena oscillate under the control of the circadian system,
      exhibiting peaks and troughs of activity across the day/night cycle. In most
      animal models, memory formation also exhibits this property, but the underlying
      neuronal and molecular mechanisms remain unclear. The dCREB2 transcription factor
      shows circadian regulated oscillations in its activity, and has been shown to be
      important for both circadian biology and memory formation. We show that the time
      of-day (TOD) of behavioral training affects Drosophila memory formation. dCREB2
      exhibits complex changes in protein levels across the daytime and nighttime, and
      these changes in protein abundance are likely to contribute to oscillations in
      dCREB2 activity and TOD effects on memory formation. 

PMID- 24744706
TI  - Corrigendum: Left temporal alpha-band activity reflects single word
      intelligibility.

PMID- 24744707
TI  - Dynamic learning and memory, synaptic plasticity and neurogenesis: an update.
AB  - Mammalian memory is the result of the interaction of millions of neurons in the
      brain and their coordinated activity. Candidate mechanisms for memory are
      synaptic plasticity changes, such as long-term potentiation (LTP). LTP is
      essentially an electrophysiological phenomenon manifested in hours-lasting
      increase on postsynaptic potentials after synapse tetanization. It is thought to
      ensure long-term changes in synaptic efficacy in distributed networks, leading to
      persistent changes in the behavioral patterns, actions and choices, which are
      often interpreted as the retention of information, i.e., memory. Interestingly,
      new neurons are born in the mammalian brain and adult hippocampal neurogenesis is
      proposed to provide a substrate for dynamic and flexible aspects of behavior such
      as pattern separation, prevention of interference, flexibility of behavior and
      memory resolution. This work provides a brief review on the memory and
      involvement of LTP and adult neurogenesis in memory phenomena. 

PMID- 24744708
TI  - Optogenetic inhibition of neurons by internal light production.
AB  - Optogenetics is an extremely powerful tool for selective neuronal
      activation/inhibition and dissection of neural circuits. However, a limitation of
      in vivo optogenetics is that an animal must be tethered to an optical fiber for
      delivery of light. Here, we describe a new method for in vivo, optogenetic
      inhibition of neural activity using an internal, animal-generated light source
      based on firefly luciferase. Two adeno-associated viruses encoding luciferase
      were tested and both produced concentration-dependent light after administration
      of the substrate, luciferin. Mice were co-infected with halorhodopsin- and
      luciferase-expressing viruses in the striatum, and luciferin administration
      significantly reduced Fos activity compared to control animals infected with
      halorhodopsin only. Recordings of neuronal activity in behaving animals confirmed
      that firing was greatly reduced after luciferin administration. Finally,
      amphetamine-induced locomotor activity was reduced in halorhodopsin/luciferase
      mice pre-injected with luciferin compared to controls. This demonstrates that
      virally encoded luciferase is able to generate sufficient light to activate
      halorhodopsin and suppress neural activity and change behavior. This approach
      could be used to generate inhibition in response to activation of specific
      molecular pathways. 

PMID- 24744710
TI  - Distributed circuits underlying anxiety.
AB  - Anxiety is of paramount importance for animals, as it allows assessment of the
      environment while minimizing exposure to potential threats. Furthermore, anxiety
      disorders are highly prevalent. Consequently, the neural circuitry underlying
      anxiety has been a topic of great interest. In this mini review, we will discuss
      current views on anxiety circuits. We will focus on rodent anxiety paradigms, but
      we will also consider results from human neuroimaging and clinical studies. We
      briefly review studies demonstrating the central role that the amygdala and the
      bed nucleus of the stria terminals (BNST) play in modulating anxiety and present
      evidence showing how the bed nucleus uses different output pathways to influence
      specific features of anxiolysis. Lastly, we propose that several brain regions,
      such as the medial prefrontal cortex (mPFC) and the ventral hippocampus (vHPC),
      act in a coordinated fashion with the amygdala and BNST, forming a distributed
      network of interconnected structures that control anxiety both in rodents and
      humans. 

PMID- 24744709
TI  - Learned helplessness and social avoidance in the Wistar-Kyoto rat.
AB  - The Wistar-Kyoto (WKY) rat is an established depression model characterized by
      elevated anxiety- and depression-like behavior across a variety of tests. Here we
      further characterized specific behavioral and functional domains relevant to
      depression that are altered in WKY rats. Moreover, since early-life experience
      potently shapes emotional behavior, we also determined whether aspects of WKYs'
      phenotype were modifiable by early-life factors using neonatal handling or
      maternal separation. We first compared WKYs' behavior to that of Sprague-Dawley
      (SD), Wistar, and Spontaneously Hypertensive (SHR) rats in: the open field test,
      elevated plus maze, novelty-suppressed feeding test, a social interaction test,
      and the forced swim test (FST). WKYs exhibited high baseline immobility in the
      FST and were the only strain to show increased immobility on FST Day 2 vs. Day 1
      (an indicator of learned helplessness). WKYs also showed greater social
      avoidance, along with enlarged adrenal glands and hearts relative to other
      strains. We next tested whether neonatal handling or early-life maternal
      separation stress influenced WKYs' behavior. Neither manipulation affected their
      anxiety- and depressive-like behaviors, likely due to a strong genetic
      underpinning of their phenotype. Our findings indicate that WKY rats are a useful
      model that captures specific functional domains relevant to clinical depression
      including: psychomotor retardation, behavioral inhibition, learned helplessness,
      social withdrawal, and physiological dysfunction. WKY rats appear to be resistant
      to early-life manipulations (i.e., neonatal handling) that are therapeutic in
      other strains, and may be a useful model for the development of personalized anti
      depressant therapies for treatment resistant depression. 

PMID- 24744711
TI  - The effects of valproic acid on appetitive and aversive instrumental learning in
      adult rats.
AB  - Antiepileptic medications are the frontline treatment for seizure conditions.
      However, these medications are not without cognitive side effects. Previously,
      our laboratory reported learning deficits in phenytoin and carbamazepine-treated
      rats. In the experiment reported here, the effects of valproic acid (VPA) have
      been studied using the same instrumental training tasks. VPA-treated rats
      displayed a severe deficit in acquiring a tone-signaled avoidance response. This
      deficit was attenuated in animals that had prior training in an appetitive
      context. Thus, this deficit is specific to learning in an aversive context, and
      does not result from difficulties in transferring associations from an appetitive
      to aversive context. Learning transfer deficits were previously observed in rats
      treated with phenytoin, and to a lesser extent, carbamazepine. On the other hand,
      rats treated with VPA fail to suppress inappropriate responsiveness across
      aversive training whether they had undergone prior appetitive training or not. 

PMID- 24744712
TI  - Scale and pattern of atrophy in the chronic stages of moderate-severe TBI.
AB  - BACKGROUND: Moderate-severe traumatic brain injury (TBI) is increasingly being
      understood as a progressive disorder, with growing evidence of reduced brain
      volume and white matter (WM) integrity as well as lesion expansion in the chronic
      phases of injury. The scale of these losses has yet to be investigated, and
      pattern of change across structures has received limited attention. OBJECTIVES:
      (1) To measure the percentage of patients in our TBI sample showing atrophy from
      5 to 20 months post-injury in the whole brain and in structures with known
      vulnerability to acute TBI, and (2) To examine relative vulnerability and
      patterns of volume loss across structures. METHODS: Fifty-six TBI patients
      [complicated mild to severe, with mean Glasgow Coma Scale (GCS) in severe range]
      underwent MRI at, on average, 5 and 20 months post-injury; 12 healthy controls
      underwent MRI twice, with a mean gap between scans of 25.4 months. Mean monthly
      percent volume change was computed for whole brain (ventricle-to-brain ratio;
      VBR), corpus callosum (CC), and right and left hippocampi (HPC). RESULTS: (1)
      Using a threshold of 2 z-scores below controls, 96% of patients showed atrophy
      across time points in at least one region; 75% showed atrophy in at least 3 of
      the 4 regions measured. (2) There were no significant differences in the
      proportion of patients who showed atrophy across structures. For those showing
      decline in VBR, there was a significant association with both the CC and the
      right HPC (P < 0.05 for both comparisons). There were also significant
      associations between those showing decline in (i) right and left HPC (P < 0.05);
      (ii) all combinations of genu, body and splenium of the CC (P < 0.05), and (iii)
      head and tail of the right HPC (P < 0.05 all sub-structure comparisons).
      CONCLUSIONS: Atrophy in chronic TBI is robust, and the CC, right HPC and left HPC
      appear equally vulnerable. Significant associations between the right and left
      HPC, and within substructures of the CC and right HPC, raise the possibility of
      common mechanisms for these regions, including transneuronal degeneration. Given
      the 96% incidence rate of atrophy, a genetic explanation is unlikely to explain
      all findings. Multiple and possibly synergistic mechanisms may explain findings.
      Atrophy has been associated with poorer functional outcomes, but recent findings
      suggest there is potential to offset this. A better, understanding of the
      underlying mechanisms could permit targeted therapy enabling better long-term
      outcomes.

PMID- 24744713
TI  - Contextualizing neuro-collaborations: reflections on a transdisciplinary fMRI lie
      detection experiment.
AB  - Recent neuroscience initiatives (including the E.U.'s Human Brain Project and the
      U.S.'s BRAIN Initiative) have reinvigorated discussions about the possibilities
      for transdisciplinary collaboration between the neurosciences, the social
      sciences, and the humanities. As STS scholars have argued for decades, however,
      such inter- and transdisciplinary collaborations are potentially fraught with
      tensions between researchers. This essay build on such claims by arguing that the
      tensions of transdisciplinary research also exist within researchers' own
      experiences of working between disciplines - a phenomenon that we call
      "disciplinary double consciousness" (DDC). Building on previous work that has
      characterized similar spaces (and especially on the Critical Neuroscience
      literature), we argue that "neuro-collaborations" inevitably engage researchers
      in DDC - a phenomenon that allows us to explore the useful dissonance that
      researchers can experience when working between a "home" discipline and a
      secondary discipline. Our case study is a five-year research project in
      functional magnetic resonance imaging (fMRI) lie detection involving a
      transdisciplinary research team made up of social scientists, a neuroscientist,
      and a humanist. In addition to theorizing neuro-collaborations from the inside
      out, this essay presents practical suggestions for developing transdisciplinary
      infrastructures that could support future neuro-collaborations. 

PMID- 24744714
TI  - Action relevance in linguistic context drives word-induced motor activity.
AB  - Many neurocognitive studies on the role of motor structures in action-language
      processing have implicitly adopted a "dictionary-like" framework within which
      lexical meaning is constructed on the basis of an invariant set of semantic
      features. The debate has thus been centered on the question of whether motor
      activation is an integral part of the lexical semantics (embodied theories) or
      the result of a post-lexical construction of a situation model (disembodied
      theories). However, research in psycholinguistics show that lexical semantic
      processing and context-dependent meaning construction are narrowly integrated. An
      understanding of the role of motor structures in action-language processing might
      thus be better achieved by focusing on the linguistic contexts under which such
      structures are recruited. Here, we therefore analyzed online modulations of grip
      force while subjects listened to target words embedded in different linguistic
      contexts. When the target word was a hand action verb and when the sentence
      focused on that action (John signs the contract) an early increase of grip force
      was observed. No comparable increase was detected when the same word occurred in
      a context that shifted the focus toward the agent's mental state (John wants to
      sign the contract). There mere presence of an action word is thus not sufficient
      to trigger motor activation. Moreover, when the linguistic context set up a
      strong expectation for a hand action, a grip force increase was observed even
      when the tested word was a pseudo-verb. The presence of a known action word is
      thus not required to trigger motor activation. Importantly, however, the same
      linguistic contexts that sufficed to trigger motor activation with pseudo-verbs
      failed to trigger motor activation when the target words were verbs with no motor
      action reference. Context is thus not by itself sufficient to supersede an
      "incompatible" word meaning. We argue that motor structure activation is part of
      a dynamic process that integrates the lexical meaning potential of a term and the
      context in the online construction of a situation model, which is a crucial
      process for fluent and efficient online language comprehension. 

PMID- 24744715
TI  - Effects of load and maintenance duration on the time course of information
      encoding and retrieval in working memory: from perceptual analysis to post
      categorization processes.
AB  - WORKING MEMORY (WM) INVOLVES THREE COGNITIVE EVENTS: information encoding,
      maintenance, and retrieval; these are supported by brain activity in a network of
      frontal, parietal and temporal regions. Manipulation of WM load and duration of
      the maintenance period can modulate this activity. Although such modulations have
      been widely studied using the event-related potentials (ERP) technique, a precise
      description of the time course of brain activity during encoding and retrieval is
      still required. Here, we used this technique and principal component analysis to
      assess the time course of brain activity during encoding and retrieval in a
      delayed match to sample task. We also investigated the effects of memory load and
      duration of the maintenance period on ERP activity. Brain activity was similar
      during information encoding and retrieval and comprised six temporal factors,
      which closely matched the latency and scalp distribution of some ERP components:
      P1, N1, P2, N2, P300, and a slow wave. Changes in memory load modulated task
      performance and yielded variations in frontal lobe activation. Moreover, the P300
      amplitude was smaller in the high than in the low load condition during encoding
      and retrieval. Conversely, the slow wave amplitude was higher in the high than in
      the low load condition during encoding, and the same was true for the N2
      amplitude during retrieval. Thus, during encoding, memory load appears to
      modulate the processing resources for context updating and post-categorization
      processes, and during retrieval it modulates resources for stimulus
      classification and context updating. Besides, despite the lack of differences in
      task performance related to duration of the maintenance period, larger N2
      amplitude and stronger activation of the left temporal lobe after long than after
      short maintenance periods were found during information retrieval. Thus, results
      regarding the duration of maintenance period were complex, and future work is
      required to test the time-based decay theory predictions.

PMID- 24744716
TI  - Assessing randomness and complexity in human motion trajectories through analysis
      of symbolic sequences.
AB  - Complexity is a hallmark of intelligent behavior consisting both of regular
      patterns and random variation. To quantitatively assess the complexity and
      randomness of human motion, we designed a motor task in which we translated
      subjects' motion trajectories into strings of symbol sequences. In the first part
      of the experiment participants were asked to perform self-paced movements to
      create repetitive patterns, copy pre-specified letter sequences, and generate
      random movements. To investigate whether the degree of randomness can be
      manipulated, in the second part of the experiment participants were asked to
      perform unpredictable movements in the context of a pursuit game, where they
      received feedback from an online Bayesian predictor guessing their next move. We
      analyzed symbol sequences representing subjects' motion trajectories with five
      common complexity measures: predictability, compressibility, approximate entropy,
      Lempel-Ziv complexity, as well as effective measure complexity. We found that
      subjects' self-created patterns were the most complex, followed by drawing
      movements of letters and self-paced random motion. We also found that
      participants could change the randomness of their behavior depending on context
      and feedback. Our results suggest that humans can adjust both complexity and
      regularity in different movement types and contexts and that this can be assessed
      with information-theoretic measures of the symbolic sequences generated from
      movement trajectories. 

PMID- 24744717
TI  - Decimal fraction representations are not distinct from natural number
      representations - evidence from a combined eye-tracking and computational
      modeling approach.
AB  - Decimal fractions comply with the base-10 notational system of natural Arabic
      numbers. Nevertheless, recent research suggested that decimal fractions may be
      represented differently than natural numbers because two number processing
      effects (i.e., semantic interference and compatibility effects) differed in their
      size between decimal fractions and natural numbers. In the present study, we
      examined whether these differences indeed indicate that decimal fractions are
      represented differently from natural numbers. Therefore, we provided an
      alternative explanation for the semantic congruity effect, namely a string length
      congruity effect. Moreover, we suggest that the smaller compatibility effect for
      decimal fractions compared to natural numbers was driven by differences in
      processing strategy (sequential vs. parallel). To evaluate this claim, we
      manipulated the tenth and hundredth digits in a magnitude comparison task with
      participants' eye movements recorded, while the unit digits remained identical.
      In addition, we evaluated whether our empirical findings could be simulated by an
      extended version of our computational model originally developed to simulate
      magnitude comparisons of two-digit natural numbers. In the eye-tracking study, we
      found evidence that participants processed decimal fractions more sequentially
      than natural numbers because of the identical leading digit. Importantly, our
      model was able to account for the smaller compatibility effect found for decimal
      fractions. Moreover, string length congruity was an alternative account for the
      prolonged reaction times for incongruent decimal pairs. Consequently, we suggest
      that representations of natural numbers and decimal fractions do not differ. 

PMID- 24744718
TI  - Assessing the quality of steady-state visual-evoked potentials for moving humans
      using a mobile electroencephalogram headset.
AB  - Recent advances in mobile electroencephalogram (EEG) systems, featuring non-prep
      dry electrodes and wireless telemetry, have enabled and promoted the applications
      of mobile brain-computer interfaces (BCIs) in our daily life. Since the brain may
      behave differently while people are actively situated in ecologically-valid
      environments versus highly-controlled laboratory environments, it remains unclear
      how well the current laboratory-oriented BCI demonstrations can be translated
      into operational BCIs for users with naturalistic movements. Understanding
      inherent links between natural human behaviors and brain activities is the key to
      ensuring the applicability and stability of mobile BCIs. This study aims to
      assess the quality of steady-state visual-evoked potentials (SSVEPs), which is
      one of promising channels for functioning BCI systems, recorded using a mobile
      EEG system under challenging recording conditions, e.g., walking. To
      systematically explore the effects of walking locomotion on the SSVEPs, this
      study instructed subjects to stand or walk on a treadmill running at speeds of 1,
      2, and 3 mile (s) per hour (MPH) while concurrently perceiving visual flickers
      (11 and 12 Hz). Empirical results of this study showed that the SSVEP amplitude
      tended to deteriorate when subjects switched from standing to walking. Such SSVEP
      suppression could be attributed to the walking locomotion, leading to distinctly
      deteriorated SSVEP detectability from standing (84.87 +/- 13.55%) to walking (1
      MPH: 83.03 +/- 13.24%, 2 MPH: 79.47 +/- 13.53%, and 3 MPH: 75.26 +/- 17.89%).
      These findings not only demonstrated the applicability and limitations of SSVEPs
      recorded from freely behaving humans in realistic environments, but also provide
      useful methods and techniques for boosting the translation of the BCI technology
      from laboratory demonstrations to practical applications. 

PMID- 24744719
TI  - Cognitive requirements of competing neuro-behavioral decision systems: some
      implications of temporal horizon for managerial behavior in organizations.
AB  - Interpretation of managerial activity in terms of neuroscience is typically
      concerned with extreme behaviors such as corporate fraud or reckless investment
      (Peterson, 2007; Wargo et al., 2010a). This paper is concerned to map out the
      neurophysiological and cognitive mechanisms at work across the spectrum of
      managerial behaviors encountered in more day-to-day contexts. It proposes that
      the competing neuro-behavioral decisions systems (CNBDS) hypothesis (Bickel et
      al., 2012b) captures well the range of managerial behaviors that can be
      characterized as hyper- or hypo-activity in either the limbically-based impulsive
      system or the frontal-cortically based executive system with the corresponding
      level of activity encountered in the alternative brain region. This pattern of
      neurophysiological responding also features in the Somatic Marker Hypothesis
      (Damasio, 1994) and in Reinforcement Sensitivity Theory (RST; Gray and
      McNaughton, 2000; McNaughton and Corr, 2004), which usefully extend the thesis,
      for example in the direction of personality. In discussing these theories, the
      paper has three purposes: to clarify the role of cognitive explanation in neuro
      behavioral decision theory, to propose picoeconomics (Ainslie, 1992) as the
      cognitive component of competing neuro-behavioral decision systems theory and to
      suggest solutions to the problems of imbalanced neurophysiological activity in
      managerial behavior. The first is accomplished through discussion of the role of
      picoeconomics in neuro-behavioral decision theory; the second, by consideration
      of adaptive-innovative cognitive styles (Kirton, 2003) in the construction of
      managerial teams, a theme that can now be investigated by a dedicated research
      program that incorporates psychometric analysis of personality types and
      cognitive styles involved in managerial decision-making and the underlying
      neurophysiological bases of such decision-making. 

PMID- 24744720
TI  - EEG-informed fMRI analysis during a hand grip task: estimating the relationship
      between EEG rhythms and the BOLD signal.
AB  - In the last decade, an increasing interest has arisen in investigating the
      relationship between the electrophysiological and hemodynamic measurements of
      brain activity, such as EEG and (BOLD) fMRI. In particular, changes in BOLD have
      been shown to be associated with changes in the spectral profile of neural
      activity, rather than with absolute power. Concurrently, recent findings showed
      that different EEG rhythms are independently related to changes in the BOLD
      signal: therefore, it would be also important to distinguish between the
      contributions of the different EEG rhythms to BOLD fluctuations when modeling the
      relationship between the two signals. Here we propose a method to perform EEG
      informed fMRI analysis where the changes in the spectral profile are modeled,
      and, at the same time, the distinction between rhythms is preserved. We compared
      our model with two other frequency-dependent regressors modeling using
      simultaneous EEG-fMRI data from healthy subjects performing a motor task. Our
      results showed that the proposed method better captures the correlations between
      BOLD signal and EEG rhythms modulations, identifying task-related, well localized
      activated volumes. Furthermore, we showed that including among the regressors
      also EEG rhythms not primarily involved in the task enhances the performance of
      the analysis, even when only correlations with BOLD signal and specific EEG
      rhythms are explored. 

PMID- 24744721
TI  - Cognitive functions of regularly cycling women may differ throughout the month,
      depending on sex hormone status; a possible explanation to conflicting results of
      studies of ADHD in females.
AB  - Attention Deficit/Hyperactivity Disorder (ADHD) is considered as a model of neuro
      developmental cognitive function. ADHD research previously studied mainly males.
      A major biological distinction between the genders is the presence of a menstrual
      cycle, which is associated with variations in sex steroid hormone levels. There
      is a growing body of literature showing that sex hormones have the ability to
      regulate intracellular signaling systems that are thought to be abnormal in ADHD.
      Thus, it is conceivable to believe that this functional interaction between sex
      hormones and molecules involved with synaptic plasticity and neurotransmitter
      systems may be associated with some of the clinical characteristics of women with
      ADHD. In spite of the impact of sex hormones on major neurotransmitter systems of
      the brain in a variety of clinical settings, the menstrual cycle is usually
      entered to statistical analyses as a nuisance or controlled for by only testing
      male samples. Evaluation of brain structure, function and chemistry over the
      course of the menstrual cycle as well as across the lifespan of women
      (premenarche, puberty, cycling period, premenopause, postmenopause) is critical
      to understanding sex differences in both normal and aberrant mental function and
      behavior. The studies of ADHD in females suggest confusing and non-consistent
      conclusions. None of these studies examined the possible relationship between
      phase of the menstrual cycle, sex hormones levels and ADHD symptoms. The
      menstrual cycle should therefore be taken into consideration in future studies in
      the neurocognitive field since it offers a unique opportunity to understand
      whether and how subtle fluctuations of sex hormones and specific combinations of
      sex hormones influence neuronal circuits implicated in the cognitive regulation
      of emotional processing. The investigation of biological models involving the
      role of estrogen, progesterone, and other sex steroids has the potential to
      generate new and improved diagnostic and treatment strategies that could change
      the course of cognitive-behavioral disorders such as ADHD. 

PMID- 24744722
TI  - Studying the Spatial Distribution of Physiological Effects on BOLD Signals Using
      Ultrafast fMRI.
AB  - The blood-oxygen-level dependent (BOLD) signal in functional MRI (fMRI) reflects
      both neuronal activations and global physiological fluctuations. These
      physiological fluctuations can be attributed to physiological low frequency
      oscillations (pLFOs), respiration, and cardiac pulsation. With typical TR values,
      i.e., 2 s or longer, the high frequency physiological signals (i.e., from
      respiration and cardiac pulsation) are aliased into the low frequency band,
      making it hard to study the individual effect of these physiological processes on
      BOLD. Recently developed multiband EPI sequences, which offer full brain coverage
      with extremely short TR values (400 ms or less) allow these physiological signals
      to be spectrally separated. In this study, we applied multiband resting state
      scans on nine healthy participants with TR = 0.4 s. The spatial distribution of
      each physiological process on BOLD fMRI was explored using their spectral
      features and independent component analysis (ICA). We found that the spatial
      distributions of different physiological processes are distinct. First, cardiac
      pulsation affects mostly the base of the brain, where high density of arteries
      exists. Second, respiration affects prefrontal and occipital areas, suggesting
      the motion associated with breathing might contribute to the noise. Finally, and
      most importantly, we found that the effects of pLFOs dominated many prominent ICA
      components, which suggests that, contrary to the popular belief that aliased
      cardiac and respiration signals are the main physiological noise source in BOLD
      fMRI, pLFOs may be the most influential physiological signals. Understanding and
      measuring these pLFOs are important for denoising and accurately modeling BOLD
      signals. 

PMID- 24744724
TI  - The neuronal response at extended timescales: long-term correlations without long
      term memory.
AB  - Long term temporal correlations frequently appear at many levels of neural
      activity. We show that when such correlations appear in isolated neurons, they
      indicate the existence of slow underlying processes and lead to explicit
      conditions on the dynamics of these processes. Moreover, although these slow
      processes can potentially store information for long times, we demonstrate that
      this does not imply that the neuron possesses a long memory of its input, even if
      these processes are bidirectionally coupled with neuronal response. We derive
      these results for a broad class of biophysical neuron models, and then fit a
      specific model to recent experiments. The model reproduces the experimental
      results, exhibiting long term (days-long) correlations due to the interaction
      between slow variables and internal fluctuations. However, its memory of the
      input decays on a timescale of minutes. We suggest experiments to test these
      predictions directly. 

PMID- 24744723
TI  - Sensing risk, fearing uncertainty: systems science approach to change.
AB  - BACKGROUND: Medicine devotes its primary focus to understanding change, from
      cells to network relationships; observations of non-linearity are inescapable.
      Recent events provide extraordinary examples of major non-linear surprises within
      the societal system: human genome-from anticipated 100,000+ genes to only
      20,000+; junk DNA-initially ignored but now proven to control genetic processes;
      economic reversals-bursting of bubbles in technology, housing, finance; foreign
      wars; relentless rise in obesity, neurodegenerative diseases. There are two
      attributes of systems science that are especially relevant to this research: One
      it offers a method for creating a structural context with a guiding path to
      pragmatic knowledge; and, two-it gives pre-eminence to sensory input capable to
      register, evaluate, and react to change. MATERIALS/METHODS: Public domain records
      of change, during the last 50 years, have been studied in the context of systems
      science, the dynamic systems model, and various cycles. RESULTS/CONCLUSIONS:
      Change is dynamic, ever-present, never isolated, and of variable impact; it
      reflects innumerable relationships among contextual systems; change can be
      perceived as risk or uncertainty depending upon how the assessment is made; risk
      is quantifiable by sensory input and generates a degree of rational optimism;
      uncertainty is not quantifiable and evokes fear; trust is key to sharing risk;
      the measurable financial credit can be a proxy for societal trust; expanding
      credit dilutes trust; when a credit bubble bursts, so will trust; absence of
      trust paralyzes systems' relationships leading to disorganized complexity which
      prevents value creation and heightens the probability of random events;
      disappearance of value, accompanied by chaos, threatens all systems. From
      personal health to economic sustainability and collective rationality, most
      examined components of the societal system were found not to be optimized and
      trust was not in evidence.

PMID- 24744725
TI  - Deformation-specific and deformation-invariant visual object recognition: pose
      vs. identity recognition of people and deforming objects.
AB  - When we see a human sitting down, standing up, or walking, we can recognize one
      of these poses independently of the individual, or we can recognize the
      individual person, independently of the pose. The same issues arise for deforming
      objects. For example, if we see a flag deformed by the wind, either blowing out
      or hanging languidly, we can usually recognize the flag, independently of its
      deformation; or we can recognize the deformation independently of the identity of
      the flag. We hypothesize that these types of recognition can be implemented by
      the primate visual system using temporo-spatial continuity as objects transform
      as a learning principle. In particular, we hypothesize that pose or deformation
      can be learned under conditions in which large numbers of different people are
      successively seen in the same pose, or objects in the same deformation. We also
      hypothesize that person-specific representations that are independent of pose,
      and object-specific representations that are independent of deformation and view,
      could be built, when individual people or objects are observed successively
      transforming from one pose or deformation and view to another. These hypotheses
      were tested in a simulation of the ventral visual system, VisNet, that uses
      temporal continuity, implemented in a synaptic learning rule with a short-term
      memory trace of previous neuronal activity, to learn invariant representations.
      It was found that depending on the statistics of the visual input, either pose
      specific or deformation-specific representations could be built that were
      invariant with respect to individual and view; or that identity-specific
      representations could be built that were invariant with respect to pose or
      deformation and view. We propose that this is how pose-specific and pose
      invariant, and deformation-specific and deformation-invariant, perceptual
      representations are built in the brain. 

PMID- 24744726
TI  - Postsynaptic localization of PSD-95 is regulated by all three pathways downstream
      of TrkB signaling.
AB  - Brain-derived neurotrophic factor (BDNF) and its receptor TrkB regulate synaptic
      plasticity. TrkB triggers three downstream signaling pathways;
      Phosphatidylinositol 3-kinase (PI3K), Phospholipase Cgamma (PLCgamma) and Mitogen
      activated protein kinases/Extracellular signal-regulated kinases (MAPK/ERK). We
      previously showed two distinct mechanisms whereby BDNF-TrkB pathway controls
      trafficking of PSD-95, which is the major scaffold at excitatory synapses and is
      critical for synapse maturation. BDNF activates the PI3K-Akt pathway and
      regulates synaptic delivery of PSD-95 via vesicular transport (Yoshii and
      Constantine-Paton, 2007). BDNF-TrkB signaling also triggers PSD-95 palmitoylation
      and its transport to synapses through the phosphorylation of the palmitoylation
      enzyme ZDHHC8 by a protein kinase C (PKC; Yoshii etal., 2011). The second study
      used PKC inhibitors chelerythrine as well as a synthetic zeta inhibitory peptide
      (ZIP) which was originally designed to block the brain-specific PKC isoform
      protein kinase Mpi (PKMpi). However, recent studies raise concerns about
      specificity of ZIP. Here, we assessed the contribution of TrkB and its three
      downstream pathways to the synaptic distribution of endogenous PSD-95 in cultured
      neurons using chemical and genetic interventions. We confirmed that TrkB, PLC,
      and PI3K were critical for the postsynaptic distribution of PSD-95. Furthermore,
      suppression of MAPK/ERK also disrupted PSD-95 expression. Next, we examined the
      contribution of PKC. While both chelerythrine and ZIP suppressed the postsynaptic
      localization of PSD-95, RNA interference for PKMpi did not have a significant
      effect. This result suggests that the ZIP peptide, widely used as the "specific"
      PKMpi antagonist by many investigators may block a PKC variant other than PKMpi
      such as PKClambda/iota. Our results indicate that TrkB regulates postsynaptic
      localization of PSD-95 through all three downstream pathways, but also recommend
      further work to identify other PKC variants that regulate palmitoylation and
      synaptic localization of PSD-95. 

PMID- 24744727
TI  - Homeostatic structural plasticity increases the efficiency of small-world
      networks.
AB  - In networks with small-world topology, which are characterized by a high
      clustering coefficient and a short characteristic path length, information can be
      transmitted efficiently and at relatively low costs. The brain is composed of
      small-world networks, and evolution may have optimized brain connectivity for
      efficient information processing. Despite many studies on the impact of topology
      on information processing in neuronal networks, little is known about the
      development of network topology and the emergence of efficient small-world
      networks. We investigated how a simple growth process that favors short-range
      connections over long-range connections in combination with a synapse formation
      rule that generates homeostasis in post-synaptic firing rates shapes neuronal
      network topology. Interestingly, we found that small-world networks benefited
      from homeostasis by an increase in efficiency, defined as the averaged inverse of
      the shortest paths through the network. Efficiency particularly increased as
      small-world networks approached the desired level of electrical activity.
      Ultimately, homeostatic small-world networks became almost as efficient as random
      networks. The increase in efficiency was caused by the emergent property of the
      homeostatic growth process that neurons started forming more long-range
      connections, albeit at a low rate, when their electrical activity was close to
      the homeostatic set-point. Although global network topology continued to change
      when neuronal activities were around the homeostatic equilibrium, the small-world
      property of the network was maintained over the entire course of development. Our
      results may help understand how complex systems such as the brain could set up an
      efficient network topology in a self-organizing manner. Insights from our work
      may also lead to novel techniques for constructing large-scale neuronal networks
      by self-organization. 

PMID- 24744728
TI  - Differential role of CSF alpha-synuclein species, tau, and Abeta42 in Parkinson's
      Disease.
AB  - There is a great interest in developing cerebrospinal fluid (CSF) biomarkers for
      diagnosis and prognosis of Parkinson's disease (PD). CSF alpha synuclein (alpha
      syn) species, namely total and oligomeric alpha-syn (t-alpha-syn and o-alpha
      syn), have shown to be of help for PD diagnosis. Preliminary evidences show that
      the combination of CSF t-alpha-syn and classical Alzheimer's disease (AD)
      biomarkers-beta-amyloid 1-42 (Abeta42), total tau (t-tau), phosphorylated tau (p
      tau)-differentiate PD patients from controls, and that reduced levels of Abeta42
      represent a predictive factor for development of cognitive deterioration in PD.
      In this prospective study carried out in 44 PD patients and 25 neurological
      controls we wanted to verify whether the combination of CSF alpha-synuclein
      species-t-alpha-syn and o-alpha-syn-and classical AD biomarkers may help in
      differentiating PD from neurological controls, and if these biomarkers may
      predict cognitive decline. The median of follow-up duration was 3 years (range: 2
      6 years). Mini Mental State Examination (MMSE) and Montreal Cognitive Assessment
      (MoCA) were used for monitoring cognitive changes along time, being administered
      once a year. Oligo/total alpha-syn ratio (o/t-alpha-syn ratio) confirmed its
      diagnostic value, significantly contributing to the discrimination of PD from
      neurological controls. A greater diagnostic accuracy was reached when combining
      o/t-alpha-syn and Abeta42/tau ratios (Sens = 0.70, Spec = 0.84, AUC = 0.82; PPV =
      0.89, NPV = 0.62, LR+ = 4.40, DOR = 12.52). Low CSF Abeta42 level was associated
      with a higher rate of MMSE and MoCA decline, confirming its role as independent
      predictive factor for cognitive decline in PD. None of the other biomarkers
      assessed (t-tau, p-tau, t-alpha-syn and o-alpha-syn) showed to have prognostic
      value. We conclude that combination of CSF o/t-alpha-syn and Abeta42/tau ratios
      improve the diagnostic accuracy of PD. PD patients showing low CSF Abeta42 levels
      at baseline are more prone to develop cognitive decline. 

PMID- 24744730
TI  - Serotonin mediation of early memory formation via 5-HT2B receptor-induced
      glycogenolysis in the day-old chick.
AB  - Investigation of the effects of serotonin on memory formation in the chick
      revealed an action on at least two 5-HT receptors. Serotonin injected
      intracerebrally produced a biphasic effect on memory consolidation with
      enhancement at low doses and inhibition at higher doses. The non-selective 5-HT
      receptor antagonist methiothepin and the selective 5-HT2B/C receptor antagonist
      SB221284 both inhibited memory, suggesting actions of serotonin on at least two
      different receptor subtypes. The 5-HT2B/C and astrocyte-specific 5-HT receptor
      agonist, fluoxetine and paroxetine, enhanced memory and the effect was attributed
      to glycogenolysis. Inhibition of glycogenolysis with a low dose of DAB (1,4
      dideoxy-1,4-imino-D-arabinitol) prevented both serotonin and fluoxetine from
      enhancing memory during short-term memory but not during intermediate memory. The
      role of serotonin on the 5-HT2B/C receptor appears to involve glycogen breakdown
      in astrocytes during short-term memory, whereas other published evidence
      attributes the second period of glycogenolysis to noradrenaline. 

PMID- 24744729
TI  - Diagnoses behind patients with hard-to-classify tremor and normal DaT-SPECT: a
      clinical follow up study.
AB  - The [(123)I]ioflupane-a dopamine transporter radioligand-SPECT (DaT-SPECT) has
      proven to be useful in the differential diagnosis of tremor. Here, we investigate
      the diagnoses behind patients with hard-to-classify tremor and normal DaT-SPECT.
      Therefore, 30 patients with tremor and normal DaT-SPECT were followed up for 2
      years. In 18 cases we were able to make a diagnosis. The residual 12 patients
      underwent a second DaT-SPECT, were then followed for additional 12 months and
      thereafter the diagnosis was reconsidered again. The final diagnoses included
      cases of essential tremor, dystonic tremor, multisystem atrophy, vascular
      parkinsonism, progressive supranuclear palsy, corticobasal degeneration, fragile
      X-associated tremor ataxia syndrome, psychogenic parkinsonism, iatrogenic
      parkinsonism and Parkinson's disease. However, for 6 patients the diagnosis
      remained uncertain. Larger series are needed to better establish the relative
      frequency of the different conditions behind these cases. 

PMID- 24744731
TI  - Acute nitric oxide synthase inhibition and endothelin-1-dependent arterial
      pressure elevation.
AB  - Key evidence that endogenous nitric oxide (NO) inhibits the continuous,
      endothelin (ET)-1-mediated drive to elevate arterial pressure includes
      demonstrations that ET-1 mediates a significant component of the pressure
      elevated by acute exposure to NO synthase (NOS) inhibitors. This review examines
      the characteristics of this pressure elevation in order to elucidate potential
      mechanisms associated with the negative regulation of ET-1 by NO and, thereby,
      provide potential insight into the vascular pathophysiology underlying NO
      dysregulation. We surmise that the magnitude of the ET-1-dependent component of
      the NOS inhibitor-elevated pressure is (1) independent of underlying arterial
      pressure and other pressor pathways activated by the NOS inhibitors and (2)
      dependent on relatively higher NOS inhibitor dose, release of stored and de novo
      synthesized ET-1, and ETA receptor-mediated increased vascular resistance. Major
      implications of these conclusions include: (1) the marked variation of the ET-1
      dependent component, i.e., from 0 to 100% of the pressure elevation, reflects the
      NO-ET-1 regulatory pathway. Thus, NOS inhibitor-mediated, ET-1-dependent pressure
      elevation in vascular pathophysiologies is an indicator of the level of
      compromised/enhanced function of this pathway; (2) NO is a more potent inhibitor
      of ET-1-mediated elevated arterial pressure than other pressor pathways, due in
      part to inhibition of intravascular pressure-independent release of ET-1. Thus,
      the ET-1-dependent component of pressure elevation in vascular pathophysiologies
      associated with NO dysregulation is of greater magnitude at higher levels of
      compromised NO. 

PMID- 24744732
TI  - Numerical Modeling Calcium and CaMKII Effects in the SA Node.
AB  - Sinoatrial node (SAN) is the primary heart pacemaker which initiates each
      heartbeat under normal conditions. Numerous experimental data have demonstrated
      that Ca(2+-) and CaMKII-dependent processes are crucially important for
      regulation of SAN cells. However, specific mechanisms of this regulation and
      their relative contribution to pacemaker function remain mainly unknown. Our
      review summarizes available data and existing numerical modeling approaches to
      understand Ca(2+) and CaMKII effects on the SAN. Data interpretation and future
      directions to address the problem are given within the coupled-clock theory,
      i.e., a modern view on the cardiac pacemaker cell function generated by a system
      of sarcolemmal and intracellular proteins. 

PMID- 24744733
TI  - Motifs in the permeation pathway of connexin channels mediate voltage and Ca (2+)
      sensing.
AB  - Connexin channels mediate electrical coupling, intercellular molecular signaling,
      and extracellular release of signaling molecules. Connexin proteins assemble
      intracellularly as hexamers to form plasma membrane hemichannels. The docking of
      two hemichannels in apposed cells forms a gap junction channel that allows direct
      electrical and selective cytoplasmic communication between adjacent cells.
      Hemichannels and junctional channels are gated by voltage, but extracellular Ca
      (2+) also gates unpaired plasma membrane hemichannels. Unlike other ion channels,
      connexin channels do not contain discrete voltage- or Ca (2+)-sensing modules
      linked to a separate pore-forming module. All studies to date indicate that
      voltage and Ca (2+) sensing are predominantly mediated by motifs that lie within
      or are exposed to the pore lumen. The sensors appear to be integral components of
      the gates, imposing an obligatory structural linkage between sensing and gating
      not commonly present in other ion channels, in which the sensors are semi
      independent domains distinct from the pore. Because of this, the structural and
      electrostatic features that define connexin channel gating also define pore
      permeability properties, and vice versa; analysis/mutagenesis of gating and of
      permeability properties are linked. This offers unique challenges and
      opportunities for elucidating mechanisms of ligand and voltage-driven gating. 

PMID- 24744734
TI  - The role of sense of effort on self-selected cycling power output.
AB  - PURPOSE: We explored the effects of the sense of effort and accompanying
      perceptions of peripheral discomfort on self-selected cycle power output under
      two different inspired O2 fractions. METHODS: On separate days, eight trained
      males cycled for 5 min at a constant subjective effort (sense of effort of '3' on
      a modified Borg CR10 scale), immediately followed by five 4-s progressive
      submaximal (sense of effort of "4, 5, 6, 7, and 8"; 40 s between bouts) and two 4
      s maximal (sense of effort of "10"; 3 min between bouts) bouts under normoxia
      (NM: fraction of inspired O2 [FiO2] 0.21) and hypoxia (HY: [FiO2] 0.13).
      Physiological (Heart Rate, arterial oxygen saturation (SpO2) and quadriceps Root
      Mean Square (RMS) electromyographical activity) and perceptual responses (overall
      peripheral discomfort, difficulty breathing and limb discomfort) were recorded.
      RESULTS: Power output and normalized quadriceps RMS activity were not different
      between conditions during any exercise bout (p > 0.05) and remained unchanged
      across time during the constant-effort cycling. SpO2 was lower, while heart rate
      and ratings of perceived difficulty breathing were higher under HY, compared to
      NM, at all time points (p < 0.05). During the constant-effort cycling, heart
      rate, overall perceived discomfort, difficulty breathing and limb discomfort
      increased with time (all p < 0.05). All variables (except SpO2) increased along
      with sense of effort during the brief progressive cycling bouts (all p < 0.05).
      During the two maximal cycling bouts, ratings of overall peripheral discomfort
      displayed an interaction between time and condition with ratings higher in the
      second bout under HY vs. NM conditions. CONCLUSION: During self-selected,
      constant-effort and brief progressive, sub-maximal, and maximal cycling bouts,
      mechanical work is regulated in parallel to the sense of effort, independently
      from peripheral sensations of discomfort.

PMID- 24744735
TI  - Plant volatile eliciting FACs in lepidopteran caterpillars, fruit flies, and
      crickets: a convergent evolution or phylogenetic inheritance?
AB  - Fatty acid amino acid conjugates (FACs), first identified in lepidopteran
      caterpillar spit as elicitors of plant volatile emission, also have been reported
      as major components in gut tracts of Drosophila melanogaster and cricket
      Teleogryllus taiwanemma. The profile of FAC analogs in these two insects was
      similar to that of tobacco hornworm Manduca sexta, showing glutamic acid
      conjugates predominantly over glutamine conjugates. The physiological function of
      FACs is presumably to enhance nitrogen assimilation in Spodoptera litura larvae,
      but in other insects it is totally unknown. Whether these insects share a common
      synthetic mechanism of FACs is also unclear. In this study, the biosynthesis of
      FACs was examined in vitro in five lepidopteran species (M. sexta, Cephonodes
      hylas, silkworm, S. litura, and Mythimna separata), fruit fly larvae and T.
      taiwanemma. The fresh midgut tissues of all of the tested insects showed the
      ability to synthesize glutamine conjugates in vitro when incubated with glutamine
      and sodium linolenate. Such direct conjugation was also observed for glutamic
      acid conjugates in all the insects but the product amount was very small and did
      not reflect the in vivo FAC patterns in each species. In fruit fly larvae, the
      predominance of glutamic acid conjugates could be explained by a shortage of
      substrate glutamine in midgut tissues, and in M. sexta, a rapid hydrolysis of
      glutamine conjugates has been reported. In crickets, we found an additional
      unique biosynthetic pathway for glutamic acid conjugates. T. taiwanemma converted
      glutamine conjugates to glutamic acid conjugates by deaminating the side chain of
      the glutamine moiety. Considering these findings together with previous results,
      a possibility that FACs in these insects are results of convergent evolution
      cannot be ruled out, but it is more likely that the ancestral insects had the
      glutamine conjugates and crickets and other insects developed glutamic acid
      conjugates in a different way. 

PMID- 24744737
TI  - Deregulation of the actin cytoskeleton and macropinocytosis in response to
      phorbol ester by the mutant protein kinase C gamma that causes spinocerebellar
      ataxia type 14.
AB  - Several missense mutations in the protein kinase Cgamma (gammaPKC) gene have been
      found to cause spinocerebellar ataxia type 14 (SCA14), an autosomal dominant
      neurodegenerative disease. gammaPKC is a neuron-specific member of the classical
      PKCs and is activated and translocated to subcellular regions as a result of
      various stimuli, including diacylglycerol synthesis, increased intracellular
      Ca(2+) and phorbol esters. We investigated whether SCA14 mutations affect the
      gammaPKC-related functions by stimulating HeLa cells with TPA (12-O
      tetradecanoylpholbol 13-acetate), a type of phorbol ester. Wild-type (WT)
      gammaPKC-GFP was translocated to the plasma membrane within 10 min of TPA
      stimulation, followed by its perinuclear translocation and cell shrinkage, in a
      PKC kinase activity- and microtubule-dependent manner. On the other hand,
      although SCA14 mutant gammaPKC-GFP exhibited a similar translocation to the
      plasma membrane, the subsequent perinuclear translocation and cell shrinkage were
      significantly impaired in response to TPA. Translocated WT gammaPKC colocalized
      with F-actin and formed large vesicular structures in the perinuclear region. The
      uptake of FITC-dextran, a marker of macropinocytosis, was promoted by TPA
      stimulation in cells expressing WT gammaPKC, and FITC-dextran was surrounded by
      gammaPKC-positive vesicles. Moreover, TPA induced the phosphorylation of MARCKS,
      which is a membrane-substrate of PKC, resulting in the translocation of
      phosphorylated MARCKS to the perinuclear region, suggesting that TPA induces
      macropinocytosis via gammaPKC activation. However, TPA failed to activate
      macropinocytosis and trigger the translocation of phosphorylated MARCKS in cells
      expressing the SCA14 mutant gammaPKC. These findings suggest that gammaPKC is
      involved in the regulation of the actin cytoskeleton and macropinocytosis in HeLa
      cells, while SCA14 mutant gammaPKC fails to regulate these processes due to its
      reduced kinase activity at the plasma membrane. This property might be involved
      in pathogenesis of SCA14. 

PMID- 24744738
TI  - Agitation predicts response of depression to botulinum toxin treatment in a
      randomized controlled trial.
AB  - In a randomized, controlled trial (n = 30), we showed that botulinum toxin
      injection to the glabellar region produces a marked improvement in the symptoms
      of major depression. We hypothesized that the mood-lifting effect was mediated by
      facial feedback mechanisms. Here we assessed if agitation, which may be
      associated with increased dynamic psychomotor activity of the facial musculature,
      can predict response to the treatment. To test this hypothesis, we re-analyzed
      the data of the scales from our previous study on a single item basis and
      compared the baseline scores in the agitation item (item 9) of the Hamilton
      Depression Rating Scale (HAM-D) between responders (n = 9) and participants who
      did not attain response (n = 6) among the recipients of onabotulinumtoxinA (n =
      15). Responders had significantly higher item 9 scores at baseline [1.56 + 0.88
      vs. 0.33 + 0.52, t (13) = 3.04, d = 1.7, p = 0.01], while no other single item of
      the HAM-D or the Beck Depression Inventory was associated with treatment
      response. The agitation score had an overall precision of 78% in predicting
      response in a receiver operating characteristic (ROC) analysis (area under the
      curve, AUC = 0.87). These data provide a link between response to botulinum toxin
      treatment with a psychomotor manifestation of depression and thereby indirect
      support of the proposed facial feedback mechanism of action. Moreover, it
      suggests that patients with agitated depression may particularly benefit from
      botulinum toxin treatment. 

PMID- 24744736
TI  - Molecular and neural mechanisms of sex pheromone reception and processing in the
      silkmoth Bombyx mori.
AB  - Male moths locate their mates using species-specific sex pheromones emitted by
      conspecific females. One striking feature of sex pheromone recognition in males
      is the high degree of specificity and sensitivity at all levels, from the primary
      sensory processes to behavior. The silkmoth Bombyx mori is an excellent model
      insect in which to decipher the underlying mechanisms of sex pheromone
      recognition due to its simple sex pheromone communication system, where a single
      pheromone component, bombykol, elicits the full sexual behavior of male moths.
      Various technical advancements that cover all levels of analysis from molecular
      to behavioral also allow the systematic analysis of pheromone recognition
      mechanisms. Sex pheromone signals are detected by pheromone receptors expressed
      in olfactory receptor neurons in the pheromone-sensitive sensilla trichodea on
      male antennae. The signals are transmitted to the first olfactory processing
      center, the antennal lobe (AL), and then are processed further in the higher
      centers (mushroom body and lateral protocerebrum) to elicit orientation behavior
      toward females. In recent years, significant progress has been made elucidating
      the molecular mechanisms underlying the detection of sex pheromones. In addition,
      extensive studies of the AL and higher centers have provided insights into the
      neural basis of pheromone processing in the silkmoth brain. This review describes
      these latest advances, and discusses what these advances have revealed about the
      mechanisms underlying the specific and sensitive recognition of sex pheromones in
      the silkmoth. 

PMID- 24744739
TI  - Postdiction: its implications on visual awareness, hindsight, and sense of
      agency.
AB  - There are a few postdictive perceptual phenomena known, in which a stimulus
      presented later seems causally to affect the percept of another stimulus
      presented earlier. While backward masking provides a classical example, the flash
      lag effect stimulates theorists with a variety of intriguing findings. The TMS
      triggered scotoma together with "backward filling-in" of it offer a unique
      neuroscientific case. Findings suggest that various visual attributes are
      reorganized in a postdictive fashion to be consistent with each other, or to be
      consistent in a causality framework. In terms of the underlying mechanisms, four
      prototypical models have been considered: the "catch up," the "reentry," the
      "different pathway" and the "memory revision" models. By extending the list of
      postdictive phenomena to memory, sensory-motor and higher-level cognition, one
      may note that such a postdictive reconstruction may be a general principle of
      neural computation, ranging from milliseconds to months in a time scale, from
      local neuronal interactions to long-range connectivity, in the complex brain. The
      operational definition of the "postdictive phenomenon" can be applicable to such
      a wide range of sensory/cognitive effects across a wide range of time scale, even
      though the underlying neural mechanisms may vary across them. This has
      significant implications in interpreting "free will" and "sense of agency" in
      functional, psychophysical and neuroscientific terms. 

PMID- 24744741
TI  - Snack food intake in ad libitum fed rats is triggered by the combination of fat
      and carbohydrates.
AB  - Snack food like potato chips substantially contributes to energy intake in
      humans. In contrast to basic food, snacks are consumed additionally to other
      meals and may thereby lead to non-homeostatic energy intake. Snack food is also
      frequently associated with hedonic hyperphagia, a food intake independent from
      hunger. Analysis of brain activity patterns by manganese-enhanced MRI has
      previously revealed that the intake of potato chips in ad libitum fed rats
      strongly activates the reward system of the rat brain, which may lead to hedonic
      hyperphagia. The purpose of the present study was to develop a two-choice
      preference test to identify molecular determinants of snack food triggering extra
      food intake in ad libitum fed rats. Different kinds of test food were presented
      three times a day for 10 min each time. To minimize the influence of organoleptic
      properties, each test food was applied in a homogenous mixture with standard
      chow. Food intake as well as food intake-related locomotor activity were analyzed
      to evaluate the effects induced by the test foods in the two-choice preference
      test. In summary, fat (F), carbohydrates (CH), and a mixture of fat and
      carbohydrates (FCH) led to a higher food intake compared to standard chow.
      Notably, potato chip test food (PC) was highly significantly preferred over
      standard chow (STD) and also over their single main macronutrients F and CH. Only
      FCH induced an intake comparable to PC. Despite its low energy density, fat-free
      potato chip test food (ffPC) was also significantly preferred over STD and CH,
      but not over F, FCH, and PC. Thus, it can be concluded that the combination of
      fat and carbohydrates is a major molecular determinant of potato chips triggering
      hedonic hyperphagia. The applied two-choice preference test will facilitate
      future studies on stimulating and suppressive effects of other food components on
      non-homeostatic food intake. 

PMID- 24744742
TI  - Is spacing really the "friend of induction"?
AB  - Inductive learning takes place when people learn a new concept or category by
      observing a variety of exemplars. Kornell and Bjork (2008) asked participants to
      learn new painting styles either by presenting different paintings of the same
      artist consecutively (massed presentation) or by mixing paintings of different
      artists (spaced presentation). In their second experiment, Kornell and Bjork
      (2008) showed with a final style recognition test, that spacing resulted in
      better inductive learning than massing. Also, by using this style recognition
      test, they ruled out the possibility that spacing merely resulted in a better
      memory for the labels of the newly learned painting styles. The findings from
      Kornell and Bjork's (2008) second experiment are important because they show that
      the benefit of spaced learning generalizes to complex learning tasks and
      outcomes, and that it is not confined to rote memory learning. However, the
      findings from Kornell and Bjork's (2008) second experiment have never been
      replicated. In the present study we performed an exact and high-powered
      replication of Kornell and Bjork's (2008) second experiment with a Web-based
      sample. Such a replication contributes to establish the reliability of the
      original finding and hence to more conclusive evidence of the spacing effect in
      inductive learning. The findings from the present replication attempt revealed a
      medium-sized advantage of spacing over massing in inductive learning, which was
      comparable to the original effect in the experiment by Kornell and Bjork (2008).
      Also, the 95% confidence intervals (CI) of the effect sizes from both experiments
      overlapped considerably. Hence, the findings from the present replication
      experiment and the original experiment clearly reinforce each other. 

PMID- 24744740
TI  - Scene analysis in the natural environment.
AB  - The problem of scene analysis has been studied in a number of different fields
      over the past decades. These studies have led to important insights into problems
      of scene analysis, but not all of these insights are widely appreciated, and
      there remain critical shortcomings in current approaches that hinder further
      progress. Here we take the view that scene analysis is a universal problem solved
      by all animals, and that we can gain new insight by studying the problems that
      animals face in complex natural environments. In particular, the jumping spider,
      songbird, echolocating bat, and electric fish, all exhibit behaviors that require
      robust solutions to scene analysis problems encountered in the natural
      environment. By examining the behaviors of these seemingly disparate animals, we
      emerge with a framework for studying scene analysis comprising four essential
      properties: (1) the ability to solve ill-posed problems, (2) the ability to
      integrate and store information across time and modality, (3) efficient recovery
      and representation of 3D scene structure, and (4) the use of optimal motor
      actions for acquiring information to progress toward behavioral goals. 

PMID- 24744743
TI  - Gaming well: links between videogames and flourishing mental health.
AB  - This paper is a review of the state of play of research linking videogaming and
      flourishing, and explores the role of videogames and technology to improve mental
      health and well-being. Its purpose is to develop understandings about the
      positive intersection of gaming and well-being, to document evidence regarding
      links between videogames and positive mental health, and to provide guidelines
      for use by other researchers as they design and use tools and games to improve
      mental health and well-being. Using Huppert's (Huppert and So, 2013) proposition
      that to flourish is more than the absence of mental disorder but rather a
      combination of feeling good and functioning effectively, resulting in high levels
      of mental well-being, and Seligman's (Seligman, 2011) PERMA theory of well-being,
      the paper identifies strengths in existing games that generate positive affect,
      positive functioning, and positive social functioning, contributing to, and
      supporting mental health and well-being. 

PMID- 24744745
TI  - Hierarchical clustering analysis of reading aloud data: a new technique for
      evaluating the performance of computational models.
AB  - DRC (Coltheart et al., 2001) and CDP++ (Perry et al., 2010) are two of the most
      successful models of reading aloud. These models differ primarily in how their
      sublexical systems convert letter strings into phonological codes. DRC adopts a
      set of grapheme-to-phoneme conversion rules (GPCs) while CDP++ uses a simple
      trained network that has been exposed to a combination of rules and the spellings
      and pronunciations of known words. Thus far the debate between fixed rules and
      learned associations has largely emphasized reaction time experiments, error
      rates in dyslexias, and item-level variance from large-scale databases. Recently,
      Pritchard et al. (2012) examined the models' non-word reading in a new way. They
      compared responses produced by the models to those produced by 45 skilled
      readers. Their item-by-item analysis is informative, but leaves open some
      questions that can be addressed with a different technique. Using hierarchical
      clustering techniques, we first examined the subject data to identify if there
      are classes of subjects that are similar to each other in their overall response
      profiles. We found that there are indeed two groups of subject that differ in
      their pronunciations for certain consonant clusters. We also tested the
      possibility that CDP++ is modeling one set of subjects well, while DRC is
      modeling a different set of subjects. We found that CDP++ does not fit any human
      reader's response pattern very well, while DRC fits the human readers as well as
      or better than any other reader. 

PMID- 24744744
TI  - Long-term memory guidance of visuospatial attention in a change-detection
      paradigm.
AB  - Visual task performance is generally stronger in familiar environments. One
      reason for this familiarity benefit is that we learn where to direct our visual
      attention and effective attentional deployment enhances performance. Visual
      working memory plays a central role in supporting long-term memory guidance of
      visuospatial attention. We modified a change detection task to create a new
      paradigm for investigating long-term memory guidance of attention. During the
      training phase, subjects viewed images in a flicker paradigm and were asked to
      detect between one and three changes in the images. The test phase required
      subjects to detect a single change in a one-shot change detection task in which
      they held all possible locations of changes in visual working memory and deployed
      attention to those locations to determine if a change occurred. Subjects detected
      significantly more changes in images for which they had been trained to detect
      the changes, demonstrating that memory of the images guided subjects in deploying
      their attention. Moreover, capacity to detect changes was greater for images that
      had multiple changes during the training phase. In Experiment 2, we observed that
      capacity to detect changes for the 3-studied change condition increased
      significantly with more study exposures and capacity was significantly higher
      than 1, indicating that subjects were able to attend to more than one location.
      Together, these findings suggest memory and attentional systems interact via
      working memory such that long-term memory can be used to direct visual spatial
      attention to multiple locations based on previous experience. 

PMID- 24744746
TI  - The role of intrinsic motivations in attention allocation and shifting.
AB  - The concepts of attention and intrinsic motivations are of great interest within
      adaptive robotic systems, and can be exploited in order to guide, activate, and
      coordinate multiple concurrent behaviors. Attention allocation strategies
      represent key capabilities of human beings, which are strictly connected with
      action selection and execution mechanisms, while intrinsic motivations directly
      affect the allocation of attentional resources. In this paper we propose a model
      of Reinforcement Learning (RL), where both these capabilities are involved. RL is
      deployed to learn how to allocate attentional resources in a behavior-based
      robotic system, while action selection is obtained as a side effect of the
      resulting motivated attentional behaviors. Moreover, the influence of intrinsic
      motivations in attention orientation is obtained by introducing rewards
      associated with curiosity drives. In this way, the learning process is affected
      not only by goal-specific rewards, but also by intrinsic motivations. 

PMID- 24744747
TI  - Timing training in three children with diplegic cerebral palsy: short- and long
      term effects on upper-limb movement organization and functioning.
AB  - Despite the great need of interventions to maintain and improve motor functions
      in children with diplegic cerebral palsy (DCP), scientific evaluations of
      existing training methods are rare. This study aimed to explore individual
      effects of synchronized metronome training (SMT) on motor timing, spatio-temporal
      movement organization, and subjective experiences of changes in upper-limb
      functions in three children with DCP. All children participated in an
      individualized 4-week/12 session SMT training regime. Measurements before
      training (Pre), after training (Post1), and at 6 months post completed training
      (Post2) were made by the applied SMT training equipment, optoelectronic
      registrations of goal-directed upper-limb movements, and a questionnaire
      assessing subjective experiences of changes in upper-limb functions and
      usability. In general, the training regime was shown to have little effect on
      motor timing. However, some positive changes in spatio-temporal movement
      organization were found. Two children also reported substantial long-lasting
      positive changes in subjective experiences of hand/arm functionality in terms of
      increased movement control and reduced muscle tone. For these children, parallel
      kinematic findings also indicated smoother and faster movement trajectories that
      remained at Post2. Although highly individualized, the shown improvements in
      upper-limb kinematics and subjective experiences of improved functionality of the
      hands/arms for two of the cases warrant further explorations of SMT outcomes in
      children with DCP. 

PMID- 24744748
TI  - Unstandardized treatment of electroencephalographic status epilepticus does not
      improve outcome of comatose patients after cardiac arrest.
AB  - OBJECTIVE: Electroencephalographic status epilepticus occurs in 9-35% of comatose
      patients after cardiac arrest. Mortality is 90-100%. It is unclear whether (some)
      seizure patterns represent a condition in which anti-epileptic treatment may
      improve outcome, or severe ischemic damage, in which treatment is futile. We
      explored current treatment practice and its effect on patients' outcome. METHODS:
      We retrospectively identified patients that were treated with anti-epileptic
      drugs from our prospective cohort study on the value of continuous
      electroencephalography (EEG) in comatose patients after cardiac arrest. Outcome
      at 6 months was dichotomized between "good" [cerebral performance category (CPC)
      1 or 2] and "poor" (CPC 3, 4, or 5). EEG analyses were done at 24 h after cardiac
      arrest and during anti-epileptic treatment. Unequivocal seizures and generalized
      periodic discharges during more than 30 min were classified as status
      epilepticus. RESULTS: Thirty-one (22%) out of 139 patients were treated with anti
      epileptic drugs (phenytoin, levetiracetam, valproate, clonazepam, propofol,
      midazolam), of whom 24 had status epilepticus. Dosages were moderate,
      barbiturates were not used, medication induced burst-suppression not achieved,
      and treatment improved electroencephalographic status epilepticus patterns
      temporarily (<6 h). Twenty-three patients treated for status epilepticus (96%)
      died. In patients with status epilepticus at 24 h, there was no difference in
      outcome between those treated with and without anti-epileptic drugs. CONCLUSION:
      In comatose patients after cardiac arrest complicated by electroencephalographic
      status epilepticus, current practice includes unstandardized, moderate treatment
      with anti-epileptic drugs. Although widely used, this does probably not improve
      patients' outcome. A randomized controlled trial to estimate the effect of
      standardized, aggressive treatment, directed at complete suppression of
      epileptiform activity during at least 24 h, is needed and in preparation.

PMID- 24744749
TI  - Nerve Transfers to Restore upper Extremity Function: A Paradigm Shift.

PMID- 24744750
TI  - The role of pregnancy-associated hormones in the development and function of
      regulatory B cells.
AB  - During mammalian pregnancy, highly specialized mechanisms of immune tolerance are
      triggered in order to allow the semi-allogeneic fetus to grow within the maternal
      uterus in harmony with the maternal immune system. Among other mechanisms,
      changes in the endocrine status have been proposed to be at least part of the
      machinery responsible for the induction of immune tolerance during pregnancy.
      Indeed, pregnancy-associated hormones, estradiol, progesterone, and human
      chorionic gonadotropin are known to confer immune suppressive capacity to innate
      as well as adaptive immune cells. Regulatory B cells, a subpopulation of B
      lymphocytes with strong immunosuppressive functions, were shown to expand during
      pregnancy. Furthermore, it is well-known that some women suffering from multiple
      sclerosis, significantly improve their symptoms during pregnancy and this was
      attributed to the effect of female sex hormones. Accordingly, estradiol protects
      mice from developing experimental autoimmune encephalomyelitis by triggering the
      expansion and activation of regulatory B cells. In this review, we discuss
      different mechanisms associated with the development, activation, and function of
      regulatory B cells with a special focus on those involving pregnancy-associated
      hormones. 

PMID- 24744751
TI  - Thyroid hormones, t3 and t4, in the brain.
AB  - Thyroid hormones (THs) are essential for fetal and post-natal nervous system
      development and also play an important role in the maintenance of adult brain
      function. Of the two major THs, T4 (3,5,3',5'-tetraiodo-l-thyronine) is
      classically viewed as an pro-hormone that must be converted to T3 (3,5,3'-tri
      iodo-l-thyronine) via tissue-level deiodinases for biological activity. THs
      primarily mediate their effects by binding to thyroid hormone receptor (TR)
      isoforms, predominantly TRalpha1 and TRbeta1, which are expressed in different
      tissues and exhibit distinctive roles in endocrinology. Notably, the ability to
      respond to T4 and to T3 differs for the two TR isoforms, with TRalpha1 generally
      more responsive to T4 than TRbeta1. TRalpha1 is also the most abundantly
      expressed TR isoform in the brain, encompassing 70-80% of all TR expression in
      this tissue. Conversion of T4 into T3 via deiodinase 2 in astrocytes has been
      classically viewed as critical for generating local T3 for neurons. However,
      deiodinase-deficient mice do not exhibit obvious defectives in brain development
      or function. Considering that TRalpha1 is well-established as the predominant
      isoform in brain, and that TRalpha1 responds to both T3 and T4, we suggest T4 may
      play a more active role in brain physiology than has been previously accepted. 

PMID- 24744752
TI  - Anaerobic hydrocarbon and fatty acid metabolism by syntrophic bacteria and their
      impact on carbon steel corrosion.
AB  - The microbial metabolism of hydrocarbons is increasingly associated with the
      corrosion of carbon steel in sulfate-rich marine waters. However, how such
      transformations influence metal biocorrosion in the absence of an electron
      acceptor is not fully recognized. We grew a marine alkane-utilizing, sulfate
      reducing bacterium, Desulfoglaeba alkanexedens, with either sulfate or
      Methanospirillum hungatei as electron acceptors, and tested the ability of the
      cultures to catalyze metal corrosion. Axenically, D. alkanexedens had a higher
      instantaneous corrosion rate and produced more pits in carbon steel coupons than
      when the same organism was grown in syntrophic co-culture with the methanogen.
      Since anaerobic hydrocarbon biodegradation pathways converge on fatty acid
      intermediates, the corrosive ability of a known fatty acid-oxidizing syntrophic
      bacterium, Syntrophus aciditrophicus was compared when grown in pure culture or
      in co-culture with a H2-utilizing sulfate-reducing bacterium (Desulfovibrio sp.,
      strain G11) or a methanogen (M. hungatei). The instantaneous corrosion rates in
      the cultures were not substantially different, but the syntrophic, sulfate
      reducing co-culture produced more pits in coupons than other combinations of
      microorganisms. Lactate-grown cultures of strain G11 had higher instantaneous
      corrosion rates and coupon pitting compared to the same organism cultured with
      hydrogen as an electron donor. Thus, if sulfate is available as an electron
      acceptor, the same microbial assemblages produce sulfide and low molecular weight
      organic acids that exacerbated biocorrosion. Despite these trends, a surprisingly
      high degree of variation was encountered with the corrosion assessments.
      Differences in biomass, initial substrate concentration, rates of microbial
      activity or the degree of end product formation did not account for the
      variations. We are forced to ascribe such differences to the metallurgical
      properties of the coupons. 

PMID- 24744754
TI  - Molecular Interactions between Complement Factor H and Its Heparin and Heparan
      Sulfate Ligands.
AB  - Complement factor H (CFH) is the major regulator of the central complement
      protein C3b in the alternative pathway of complement activation. A molecular view
      of the CFH interaction with native heparan sulfate (HS) is central for
      understanding the mechanism of how surface-bound CFH interacts with C3b bound to
      host cell surfaces. HS is composed of sulfated heparin-like S-regions that
      alternate with desulfated NA-regions. Solution structural studies of heparin
      (equivalent to the S-regions) and desulfated HS (the NA-regions) by scattering
      and ultracentrifugation showed that each structure was mostly extended and
      partially bent, but with greater bending and flexibility in the NA-regions
      compared to the S-regions. Their solution structures have been deposited in the
      Protein Data Bank. The largest HS oligosaccharides showed more bent and flexible
      structures than those for heparin. A folded-back domain structure for the
      solution structure of the 20 domains in CFH was determined likewise. CFH binds to
      the S-regions but less so to the NA-regions of HS. The bivalent interaction of
      CFH-heparin was observed by ultracentrifugation, and binding studies of CFH
      fragments with heparin-coated sensor chips. In common with other CFH interactions
      with its physiological and pathophysiological ligands, the CFH-heparin and CFH
      C3b interactions have moderate micromolar dissociation constants K D, meaning
      that these complexes do not fully form in vivo. The combination of the solution
      structures and binding studies indicated a two-site interaction model of CFH with
      heparin at cell surfaces. By this, the bivalent binding of CFH to a cell surface
      is co-operative. Defective interactions at either of the two independent CFH
      heparin sites reduce the CFH interaction with surface-bound C3b and lead to
      immune disorders. 

PMID- 24744753
TI  - HIV-1 Vpr-a still "enigmatic multitasker".
AB  - Like other HIV-1 auxiliary proteins, Vpr is conserved within all the human (HIV
      1, HIV-2) and simian (SIV) immunodeficiency viruses. However, Vpr and homologous
      HIV-2, and SIV Vpx are the only viral auxiliary proteins specifically
      incorporated into virus particles through direct interaction with the Gag
      precursor, indicating that this presence in the core of the mature virions is
      mainly required for optimal establishment of the early steps of the virus life
      cycle in the newly infected cell. In spite of its small size, a plethora of
      effects and functions have been attributed to Vpr, including induction of cell
      cycle arrest and apoptosis, modulation of the fidelity of reverse transcription,
      nuclear import of viral DNA in macrophages and other non-dividing cells, and
      transcriptional modulation of viral and host cell genes. Even if some more recent
      studies identified a few cellular targets that HIV-1 Vpr may utilize in order to
      perform its different tasks, the real role and functions of Vpr during the course
      of natural infection are still enigmatic. In this review, we will summarize the
      main reported functions of HIV-1 Vpr and their significance in the context of the
      viral life cycle. 

PMID- 24744755
TI  - Human dendritic cell functional specialization in steady-state and inflammation.
AB  - Dendritic cells (DC) represent a heterogeneous population of antigen-presenting
      cells that are crucial in initiating and shaping immune responses. Although all
      DC are capable of antigen-uptake, processing, and presentation to T cells, DC
      subtypes differ in their origin, location, migration patterns, and specialized
      immunological roles. While in recent years, there have been rapid advances in
      understanding DC subset ontogeny, development, and function in mice, relatively
      little is known about the heterogeneity and functional specialization of human DC
      subsets, especially in tissues. In steady-state, DC progenitors deriving from the
      bone marrow give rise to lymphoid organ-resident DC and to migratory tissue DC
      that act as tissue sentinels. During inflammation additional DC and monocytes are
      recruited to the tissues where they are further activated and promote T helper
      cell subset polarization depending on the environment. In the current review, we
      will give an overview of the latest developments in human DC research both in
      steady-state and under inflammatory conditions. In this context, we review recent
      findings on DC subsets, DC-mediated cross-presentation, monocyte-DC
      relationships, inflammatory DC development, and DC-instructed T-cell
      polarization. Finally, we discuss the potential role of human DC in chronic
      inflammatory diseases. 

PMID- 24744756
TI  - Effects of Peptide on NK cell-mediated MHC I recognition.
AB  - The inhibitory receptors for MHC class I have a central role in controlling
      natural killer (NK) cell activity. Soon after their discovery, it was found that
      these receptors have a degree of peptide selectivity. Such peptide selectivity
      has been demonstrated for all inhibitory killer cell immunoglobulin-like receptor
      (KIR) tested to date, certain activating KIR, and also members of the C-type
      lectin-like family of receptors. This selectivity is much broader than the
      peptide specificity of T cell receptors, with NK cell receptors recognizing
      peptide motifs, rather than individual peptides. Inhibitory receptors on NK cells
      can survey the peptide:MHC complexes expressed on the surface of target cells,
      therefore subsequent transduction of an inhibitory signal depends on the overall
      peptide content of these MHC class I complexes. Functionally, KIR-expressing NK
      cells have been shown to be unexpectedly sensitive to changes in the peptide
      content of MHC class I, as peptide:MHC class I complexes that weakly engage KIR
      can antagonize the inhibitory signals generated by engagement of stronger KIR
      binding peptide:MHC class I complexes. This property provides KIR-expressing NK
      cells with the potential to recognize changes in the peptide:MHC class I
      repertoire, which may occur during viral infections and tumorigenesis. By
      contrast, in the presence of HLA class I leader peptides, virus-derived peptides
      can induce a synergistic inhibition of CD94:NKG2A-expressing NK cells through
      recruitment of CD94 in the absence of NKG2A. On the other hand, CD94:NKG2A
      positive NK cells can be exquisitely sensitive to changes in the levels of MHC
      class I. Peptide antagonism and sensitivity to changes in MHC class I levels are
      properties that distinguish KIR and CD94:NKG2A. The subtle difference in the
      properties of NK cells expressing these receptors provides a rationale for having
      complementary inhibitory receptor systems for MHC class I. 

PMID- 24744757
TI  - Live vaccination tactics: possible approaches for controlling visceral
      leishmaniasis.
AB  - Vaccination with durable immunity is the main goal and fundamental to control
      leishmaniasis. To stimulate the immune response, small numbers of parasites are
      necessary to be presented in the mammalian host. Similar to natural course of
      infection, strategy using live vaccine is more attractive when compared to other
      approaches. Live vaccines present the whole spectrum of antigens to the host
      immune system in the absence of any adjuvant. Leishmanization was the first
      effort for live vaccination and currently used in a few countries against
      cutaneous leishmaniasis, in spite of their obstacle and safety. Then, live
      attenuated vaccines developed with similar promotion of creating long-term
      immunity in the host with lower side effect. Different examples of attenuated
      strains are generated through long-term in vitro culturing, culturing under drug
      pressure, temperature sensitivity, and chemical mutagenesis, but none is safe
      enough and their revision to virulent form is possible. Attenuation through
      genetic manipulation and disruption of virulence factors or essential enzymes for
      intracellular survival are among other approaches that are intensively under
      study. Other designs to develop live vaccines for visceral form of leishmaniasis
      are utilization of live avirulent microorganisms such as Lactococcus lactis,
      Salmonella enterica, and Leishmania tarentolae called as vectored vaccine.
      Apparently, these vaccines are intrinsically safer and can harbor the candidate
      antigens in their genome through different genetic manipulation and create more
      potential to control Leishmania parasite as an intracellular pathogen. 

PMID- 24744758
TI  - Toll-like receptors and skin cancer.

PMID- 24744760
TI  - Immunophenotype of normal and myelomatous plasma-cell subsets.
AB  - Plasma cells (PCs) are essentially characterized by the co-expression of CD138
      and CD38, which allows their identification in flow cytometry in bone marrow
      (BM), peripheral blood, or cell suspensions from tissues. These terminally
      differentiated B-cells may lose the expression of surface CD19 and that of CD20
      while retaining CD27. When malignant, they can gain a number of other markers
      such as CD28, CD33, CD56, or CD117 and lose CD27. Moreover, since each PC is only
      able to produce a single type of immunoglobulins (Igs), they display isotypic
      restriction and clonal malignant PCs can be further characterized by their
      homogeneous expression of either kappa or lambda light chains. In multiple
      myeloma (MM), such PC clones produce the Ig identified in plasma as an abnormal
      peak. In the BM where they essentially accumulate, these PCs may however display
      various immunophenotypes. The latter were explored in a two-way approach.
      Firstly, the various subsets delineated by the selective or common expression of
      CD19 together with combined CD56/CD28 were explored in normal and MM BM. Then,
      other aberrant markers' expression was investigated, i.e., CD20, CD27, CD33,
      CD56, CD117. These data were compared to literature information. They underline
      the vast heterogeneity of MM PCs possibly accounting for the various answers to
      therapy of MM patients. 

PMID- 24744759
TI  - The HPA - Immune Axis and the Immunomodulatory Actions of Glucocorticoids in the
      Brain.
AB  - In response to physiological and psychogenic stressors, the hypothalamic
      pituitary-adrenal (HPA) axis orchestrates the systemic release of glucocorticoids
      (GCs). By virtue of nearly ubiquitous expression of the GC receptor and the
      multifaceted metabolic, cardiovascular, cognitive, and immunologic functions of
      GCs, this system plays an essential role in the response to stress and
      restoration of an homeostatic state. GCs act on almost all types of immune cells
      and were long recognized to perform salient immunosuppressive and anti
      inflammatory functions through various genomic and non-genomic mechanisms. These
      renowned effects of the steroid hormone have been exploited in the clinic for the
      past 70 years and synthetic GC derivatives are commonly used for the therapy of
      various allergic, autoimmune, inflammatory, and hematological disorders. The role
      of the HPA axis and GCs in restraining immune responses across the organism is
      however still debated in light of accumulating evidence suggesting that GCs can
      also have both permissive and stimulatory effects on the immune system under
      specific conditions. Such paradoxical actions of GCs are particularly evident in
      the brain, where substantial data support either a beneficial or detrimental role
      of the steroid hormone. In this review, we examine the roles of GCs on the innate
      immune system with a particular focus on the CNS compartment. We also dissect the
      numerous molecular mechanisms through which GCs exert their effects and discuss
      the various parameters influencing the paradoxical immunomodulatory functions of
      GCs in the brain. 

PMID- 24744761
TI  - Orchestration of an uncommon maturation cascade of the house dust mite protease
      allergen quartet.
AB  - In more than 20% of the world population, sensitization to house dust mite
      allergens triggers typical allergic diseases such as allergic rhinitis and
      asthma. Amongst the 23 mite allergen groups hitherto identified, group 1 is
      cysteine proteases belonging to the papain-like family whereas groups 3, 6, and 9
      are serine proteases displaying trypsin, chymotrypsin, and collagenolytic
      activities, respectively. While these proteases are more likely to be involved in
      the mite digestive system, they also play critical roles in the initiation and in
      the chronicity of the allergic response notably through the activation of innate
      immune pathways. All these allergenic proteases are expressed in mite as inactive
      precursor form. Until recently, the exact mechanisms of their maturation into
      active proteases remained to be fully elucidated. Recent breakthroughs in the
      understanding of the activation mechanisms of mite allergenic protease precursors
      have highlighted an uncommon and unique maturation pathway orchestrated by group
      1 proteases that tightly regulates the proteolytic activities of groups 1, 3, 6,
      and 9 through complex intra- or inter-molecular mechanisms. This review presents
      and discusses the currently available knowledge of the activation mechanisms of
      group 1, 3, 6, and 9 allergens of Dermatophagoides pteronyssinus laying special
      emphasis on their localization, regulation, and interconnection. 

PMID- 24744762
TI  - Antigen cross-presentation of immune complexes.
AB  - The ability of dendritic cells (DCs) to cross-present tumor antigens has long
      been a focus of interest to physicians, as well as basic scientists, that aim to
      establish efficient cell-based cancer immune therapy. A prerequisite for
      exploiting this pathway for therapeutic purposes is a better understanding of the
      mechanisms that underlie the induction of tumor-specific cytotoxic T-lymphocyte
      (CTL) responses when initiated by DCs via cross-presentation. The ability of
      humans DC to perform cross-presentation is of utmost interest, as this cell type
      is a main target for cell-based immunotherapy in humans. The outcome of a cross
      presentation event is guided by the nature of the antigen, the form of antigen
      uptake, and the subpopulation of DCs that performs presentation. Generally,
      CD8alpha(+) DCs are considered to be the most potent cross-presenting DCs. This
      paradigm, however, only applies to soluble antigens. During adaptive immune
      responses, immune complexes form when antibodies interact with their specific
      epitopes on soluble antigens. Immunoglobulin G (IgG) immune complexes target Fc
      gamma receptors on DCs to shuttle exogenous antigens efficiently into the cross
      presentation pathway. This receptor-mediated cross-presentation pathway is a well
      described route for the induction of strong CD8(+) T cell responses. IgG-mediated
      cross-presentation is intriguing because it permits the CD8(-) DCs, which are
      commonly considered to be weak cross-presenters, to efficiently cross-present.
      Engaging multiple DC subtypes for cross-presentation might be a superior strategy
      to boost CTL responses in vivo. We here summarize our current understanding of
      how DCs use IgG-complexed antigens for the efficient induction of CTL responses.
      Because of its importance for human cell therapy, we also review the recent
      advances in the characterization of cross-presentation properties of human DC
      subsets. 

PMID- 24744763
TI  - Recognition strategies of group 3 innate lymphoid cells.
AB  - During the early phase of an inflammatory response, innate cells can use
      different strategies to sense environmental danger. These include the direct
      interaction of specific activating receptors with pathogen-encoded/danger
      molecules or the engagement of cytokine receptors by pro-inflammatory mediators
      produced by antigen presenting cells in the course of the infection. These
      general recognition strategies, which have been extensively described for innate
      myeloid cells, are shared by innate lymphoid cells (ILC), such as Natural Killer
      (NK) cells. The family of ILC has recently expanded with the discovery of group 2
      (ILC2) and group 3 ILC (ILC3), which play an important role in the defense
      against extracellular pathogens. Although ILC3 and NK cells share some phenotypic
      characteristics, the recognition strategies employed by the various ILC3 subsets
      have been only partially characterized. In this review, we will describe and
      comparatively discuss how ILC3 sense environmental cues and how the triggering of
      different receptors may regulate their functional behavior during an immune
      response. 

PMID- 24744766
TI  - Inflorescence development in tomato: gene functions within a zigzag model.
AB  - Tomato is a major crop plant and several mutants have been selected for breeding
      but also for isolating important genes that regulate flowering and sympodial
      growth. Besides, current research in developmental biology aims at revealing
      mechanisms that account for diversity in inflorescence architectures. We
      therefore found timely to review the current knowledge of the genetic control of
      flowering in tomato and to integrate the emerging network into modeling attempts.
      We developed a kinetic model of the tomato inflorescence development where each
      meristem was represented by its "vegetativeness" (V), reflecting its maturation
      state toward flower initiation. The model followed simple rules: maturation
      proceeded continuously at the same rate in every meristem (dV); floral transition
      and floral commitment occurred at threshold levels of V; lateral meristems were
      initiated with a gain of V (DeltaV) relative to the V level of the meristem from
      which they derived. This last rule created a link between successive meristems
      and gave to the model its zigzag shape. We next exploited the model to explore
      the diversity of morphotypes that could be generated by varying dV and DeltaV and
      matched them with existing mutant phenotypes. This approach, focused on the
      development of the primary inflorescence, allowed us to elaborate on the genetic
      regulation of the kinetic model of inflorescence development. We propose that the
      lateral inflorescence meristem fate in tomato is more similar to an immature
      flower meristem than to the inflorescence meristem of Arabidopsis. In the last
      part of our paper, we extend our thought to spatial regulators that should be
      integrated in a next step for unraveling the relationships between the different
      meristems that participate to sympodial growth. 

PMID- 24744765
TI  - Trehalose-6-phosphate and SnRK1 kinases in plant development and signaling: the
      emerging picture.
AB  - Carbohydrates, or sugars, regulate various aspects of plant growth through
      modulation of cell division and expansion. Besides playing essential roles as
      sources of energy for growth and as structural components of cells, carbohydrates
      also regulate the timing of expression of developmental programs. The
      disaccharide trehalose is used as an energy source, as a storage and transport
      molecule for glucose, and as a stress-responsive compound important for cellular
      protection during stress in all kingdoms. Trehalose, however, is found in very
      low amounts in most plants, pointing to a signaling over metabolic role for this
      non-reducing disaccharide. In the last decade, trehalose-6-phosphate (T6P), an
      intermediate in trehalose metabolism, has been shown to regulate embryonic and
      vegetative development, flowering time, meristem determinacy, and cell fate
      specification in plants. T6P acts as a global regulator of metabolism and
      transcription promoting plant growth and triggering developmental phase
      transitions in response to sugar availability. Among the T6P targets are members
      of the Sucrose-non-fermenting1-related kinase1 (SnRK1) family, which are sensors
      of energy availability and inhibit plant growth and development during metabolic
      stress to maintain energy homeostasis. In this review, we will discuss the
      opposite roles of the sugar metabolite T6P and the SnRK1 kinases in the
      regulation of developmental phase transitions in response to carbohydrate levels.
      We will focus on how these two global regulators of metabolic processes integrate
      environmental cues and interact with hormonal signaling pathways to modulate
      plant development. 

PMID- 24744767
TI  - Ubiquitin chain topology in plant cell signaling: a new facet to an evergreen
      story.
AB  - Ubiquitin is a peptide modifier able to form polymers of varying length and
      linkage as part of a powerful signaling system. Perhaps the best-known aspect of
      this protein's function is as the driver of targeted protein degradation through
      the Ubiquitin Proteasome System (UPS). Through the formation of lysine 48-linked
      polyubiquitin chains, it is able to direct the degradation of tagged proteins by
      the 26S proteasome, indirectly controlling many processes within the cell.
      However, recent research has indicated that ubiquitin performs a multitude of
      other roles within the cell beyond protein degradation. It is able to form 6
      other "atypical" linkages though lysine residues at positions 6, 11, 27, 29, 33,
      and 63. These atypical chains perform a range of diverse functions, including the
      regulation of iron uptake in response to perceived deficiency, repair of double
      stranded breaks in the DNA, and regulation of the auxin response through the non
      proteasomal degradation of auxin efflux carrier protein PIN1. This review
      explores the role ubiquitin chain topology plays in plant cellular function. We
      aim to highlight the importance of these varying functions and the future
      challenges to be encountered within this field. 

PMID- 24744768
TI  - Generation of boron-deficiency-tolerant tomato by overexpressing an Arabidopsis
      thaliana borate transporter AtBOR1.
AB  - Nutrient deficiency in soil poses a widespread agricultural problem. Boron (B) is
      an essential micronutrient in plants, and its deficiency causes defects in both
      vegetative and reproductive growth in various crops in the field. In Arabidopsis
      thaliana, increased expression of a major borate transporter gene AtBOR1 or boric
      acid channel gene AtNIP5;1 improves plant growth under B-deficient conditions. In
      this study, we examined whether high expression of a borate transporter gene
      increases B accumulation in shoots and improves the growth of tomato plant, a
      model of fruit-bearing crops, under B-deficient conditions. We established three
      independent transgenic tomato plants lines expressing AtBOR1 using Agrobacterium
      mediated transformation of tomato (Solanum lycopersicum L. cv. Micro-Tom).
      Reverse transcription-polymerase chain reaction (RT-PCR) analysis confirmed that
      two lines (Line 1 and Line 2) more strongly expressed AtBOR1 than Line 3. Wild
      type plants and the transgenic plants were grown hydroponically under B
      sufficient and B-deficient conditions. Wild-type and Line 3 (weakly expressing
      transgenic line) showed a defect in shoot growth under B-deficient conditions,
      especially in the development of new leaves. However, seedlings of Line 1 and
      Line 2, the transgenic lines showing strong AtBOR1 expression, did not show the B
      deficiency phenotype in newly developing leaves. In agreement with this
      phenotype, shoot biomass under low-B conditions was higher in the strongly
      expressing AtBOR1 line. B concentrations in leaves or fruits were also higher in
      Line 2 and Line 1. The present study demonstrates that strong expression of
      AtBOR1 improved growth in tomato under B-deficient conditions. 

PMID- 24744764
TI  - Mn-euvering manganese: the role of transporter gene family members in manganese
      uptake and mobilization in plants.
AB  - Manganese (Mn), an essential trace element, is important for plant health. In
      plants, Mn serves as a cofactor in essential processes such as photosynthesis,
      lipid biosynthesis and oxidative stress. Mn deficient plants exhibit decreased
      growth and yield and are more susceptible to pathogens and damage at freezing
      temperatures. Mn deficiency is most prominent on alkaline soils with
      approximately one third of the world's soils being too alkaline for optimal crop
      production. Despite the importance of Mn in plant development, relatively little
      is known about how it traffics between plant tissues and into and out of
      organelles. Several gene transporter families have been implicated in Mn
      transport in plants. These transporter families include NRAMP (natural resistance
      associated macrophage protein), YSL (yellow stripe-like), ZIP (zinc regulated
      transporter/iron-regulated transporter [ZRT/IRT1]-related protein), CAX (cation
      exchanger), CCX (calcium cation exchangers), CDF/MTP (cation diffusion
      facilitator/metal tolerance protein), P-type ATPases and VIT (vacuolar iron
      transporter). A combination of techniques including mutant analysis and
      Synchrotron X-ray Fluorescence Spectroscopy can assist in identifying essential
      transporters of Mn. Such knowledge would vastly improve our understanding of
      plant Mn homeostasis. 

PMID- 24744769
TI  - Ensemble inference by integrative cancer networks.

PMID- 24744770
TI  - Evaluating the impact of genotype errors on rare variant tests of association.
AB  - The new class of rare variant tests has usually been evaluated assuming perfect
      genotype information. In reality, rare variant genotypes may be incorrect, and so
      rare variant tests should be robust to imperfect data. Errors and uncertainty in
      SNP genotyping are already known to dramatically impact statistical power for
      single marker tests on common variants and, in some cases, inflate the type I
      error rate. Recent results show that uncertainty in genotype calls derived from
      sequencing reads are dependent on several factors, including read depth, calling
      algorithm, number of alleles present in the sample, and the frequency at which an
      allele segregates in the population. We have recently proposed a general
      framework for the evaluation and investigation of rare variant tests of
      association, classifying most rare variant tests into one of two broad categories
      (length or joint tests). We use this framework to relate factors affecting
      genotype uncertainty to the power and type I error rate of rare variant tests. We
      find that non-differential genotype errors (an error process that occurs
      independent of phenotype) decrease power, with larger decreases for extremely
      rare variants, and for the common homozygote to heterozygote error. Differential
      genotype errors (an error process that is associated with phenotype status), lead
      to inflated type I error rates which are more likely to occur at sites with more
      common homozygote to heterozygote errors than vice versa. Finally, our work
      suggests that certain rare variant tests and study designs may be more robust to
      the inclusion of genotype errors. Further work is needed to directly integrate
      genotype calling algorithm decisions, study costs and test statistic choices to
      provide comprehensive design and analysis advice which appropriately accounts for
      the impact of genotype errors. 

PMID- 24744773
TI  - Research on WNN modeling for gold price forecasting based on improved artificial
      bee colony algorithm.
AB  - Gold price forecasting has been a hot issue in economics recently. In this work,
      wavelet neural network (WNN) combined with a novel artificial bee colony (ABC)
      algorithm is proposed for this gold price forecasting issue. In this improved
      algorithm, the conventional roulette selection strategy is discarded. Besides,
      the convergence statuses in a previous cycle of iteration are fully utilized as
      feedback messages to manipulate the searching intensity in a subsequent cycle.
      Experimental results confirm that this new algorithm converges faster than the
      conventional ABC when tested on some classical benchmark functions and is
      effective to improve modeling capacity of WNN regarding the gold price
      forecasting scheme. 

PMID- 24744771
TI  - Circularly permuted tRNA genes: their expression and implications for their
      physiological relevance and development.
AB  - A number of genome analyses and searches using programs that focus on the RNA
      specific bulge-helix-bulge (BHB) motif have uncovered a wide variety of disrupted
      tRNA genes. The results of these analyses have shown that genetic information
      encoding functional RNAs is described in the genome cryptically and is retrieved
      using various strategies. One such strategy is represented by circularly permuted
      tRNA genes, in which the sequences encoding the 5'-half and 3'-half of the
      specific tRNA are separated and inverted on the genome. Biochemical analyses have
      defined a processing pathway in which the termini of tRNA precursors (pre-tRNAs)
      are ligated to form a characteristic circular RNA intermediate, which is then
      cleaved at the acceptor-stem to generate the typical cloverleaf structure with
      functional termini. The sequences adjacent to the processing site located between
      the 3'-half and the 5'-half of pre-tRNAs potentially form a BHB motif, which is
      the dominant recognition site for the tRNA-intron splicing endonuclease,
      suggesting that circularization of pre-tRNAs depends on the splicing machinery.
      Some permuted tRNAs contain a BHB-mediated intron in their 5'- or 3'-half,
      meaning that removal of an intron, as well as swapping of the 5'- and 3'-halves,
      are required during maturation of their pre-tRNAs. To date, 34 permuted tRNA
      genes have been identified from six species of unicellular algae and one
      archaeon. Although their physiological significance and mechanism of development
      remain unclear, the splicing system of BHB motifs seems to have played a key role
      in the formation of permuted tRNA genes. In this review, current knowledge of
      circularly permuted tRNA genes is presented and some unanswered questions
      regarding these species are discussed. 

PMID- 24744774
TI  - Robust fault detection of wind energy conversion systems based on dynamic neural
      networks.
AB  - Occurrence of faults in wind energy conversion systems (WECSs) is inevitable. In
      order to detect the occurred faults at the appropriate time, avoid heavy economic
      losses, ensure safe system operation, prevent damage to adjacent relevant
      systems, and facilitate timely repair of failed components; a fault detection
      system (FDS) is required. Recurrent neural networks (RNNs) have gained a
      noticeable position in FDSs and they have been widely used for modeling of
      complex dynamical systems. One method for designing an FDS is to prepare a
      dynamic neural model emulating the normal system behavior. By comparing the
      outputs of the real system and neural model, incidence of the faults can be
      identified. In this paper, by utilizing a comprehensive dynamic model which
      contains both mechanical and electrical components of the WECS, an FDS is
      suggested using dynamic RNNs. The presented FDS detects faults of the generator's
      angular velocity sensor, pitch angle sensors, and pitch actuators. Robustness of
      the FDS is achieved by employing an adaptive threshold. Simulation results show
      that the proposed scheme is capable to detect the faults shortly and it has very
      low false and missed alarms rate. 

PMID- 24744772
TI  - RasGRP Ras guanine nucleotide exchange factors in cancer.
AB  - RasGRP proteins are activators of Ras and other related small GTPases by the
      virtue of functioning as guanine nucleotide exchange factors (GEFs). In
      vertebrates, four RasGRP family members have been described. RasGRP-1 through -4
      share many structural domains but there are also subtle differences between each
      of the different family members. Whereas SOS RasGEFs are ubiquitously expressed,
      RasGRP proteins are expressed in distinct patterns, such as in different cells of
      the hematopoietic system and in the brain. Most studies have concentrated on the
      role of RasGRP proteins in the development and function of immune cell types
      because of the predominant RasGRP expression profiles in these cells and the
      immune phenotypes of mice deficient for Rasgrp genes. However, more recent
      studies demonstrate that RasGRPs also play an important role in tumorigenesis.
      Examples are skin- and hematological-cancers but also solid malignancies such as
      melanoma or prostate cancer. These novel studies bring up many new and unanswered
      questions related to the molecular mechanism of RasGRP-driven oncogenesis, such
      as new receptor systems that RasGRP appears to respond to as well as regulatory
      mechanism for RasGRP expression that appear to be perturbed in these cancers.
      Here we will review some of the known aspects of RasGRP biology in lymphocytes
      and will discuss the exciting new notion that RasGRP Ras exchange factors play a
      role in oncogenesis downstream of various growth factor receptors.

PMID- 24744775
TI  - Mental mechanisms for topics identification.
AB  - Topics identification (TI) is the process that consists in determining the main
      themes present in natural language documents. The current TI modeling paradigm
      aims at acquiring semantic information from statistic properties of large text
      datasets. We investigate the mental mechanisms responsible for the identification
      of topics in a single document given existing knowledge. Our main hypothesis is
      that topics are the result of accumulated neural activation of loosely organized
      information stored in long-term memory (LTM). We experimentally tested our
      hypothesis with a computational model that simulates LTM activation. The model
      assumes activation decay as an unavoidable phenomenon originating from the
      bioelectric nature of neural systems. Since decay should negatively affect the
      quality of topics, the model predicts the presence of short-term memory (STM) to
      keep the focus of attention on a few words, with the expected outcome of
      restoring quality to a baseline level. Our experiments measured topics quality of
      over 300 documents with various decay rates and STM capacity. Our results showed
      that accumulated activation of loosely organized information was an effective
      mental computational commodity to identify topics. It was furthermore confirmed
      that rapid decay is detrimental to topics quality but that limited capacity STM
      restores quality to a baseline level, even exceeding it slightly. 

PMID- 24744776
TI  - Functional outcomes and quality of life after restorative proctocolectomy in
      paediatric patients: a case-control study.
AB  - Background. Restorative proctocolectomy with ileal-pouch anal anastomosis (IPAA)
      has some peculiarities in paediatric ulcerative colitis (UC). Aims. The primary
      aim was to compare the bowel function of patients undergoing IPAA between those
      operated on in childhood and adulthood. The secondary aim was to compare the
      quality of life (QoL) and outcomes for children between medical and surgical
      therapies. Method. Children undergoing IPAA were compared with adult patients
      undergoing IPAA between 2007 and 2012. Function was assessed 1 year after
      ileostomy closure. Function and QoL of medically managed paediatric patients were
      compared with their surgical counterparts. Results. Twelve paediatric IPAA
      patients were compared with 24 adult ones. Acute presentation was common in the
      former, usually after failed biological treatment. Recurrent pouchitis was more
      frequent in children. Younger patients exhibited a trend toward better
      discrimination and continence. QoL was excellent in both groups. Twelve medically
      treated children were enrolled for secondary aim. Functioning was similar in IPAA
      and medically managed children, but the former had a better QoL, confirmed by
      parents' perception. Conclusions. Similar function is achieved by IPAA in
      childhood or adulthood. IPAA may offer a better QoL compared to prolonged medical
      management. The beneficial effects of IPAA experienced by children were similarly
      observed by their parents. 

PMID- 24744778
TI  - Sugammadex and ideal body weight in bariatric surgery: the debate continues.

PMID- 24744777
TI  - Frequent abdominal pain in childhood and youth: a systematic review of
      psychophysiological characteristics.
AB  - Background. Frequent abdominal pain (AP) in children and adolescents is often
      designated as functional gastrointestinal disorder. In contrast to research on
      psychological and social influences on the experience of AP in this population,
      psychophysiological features such as function of the autonomic nervous system,
      the central nervous system, or the endocrine system have rarely been studied.
      Methods. We conducted a systematic literature search for peer-reviewed journal
      articles referring to children with AP between 4 and 18 years. Studies on
      experimental baseline characteristics or reactivity of psychophysiological
      outcome parameters (autonomous nervous system, central nervous system, and
      endocrine parameters) were included. Key Results. Twelve of 18 included studies
      found psychophysiological differences between children with AP and healthy ones.
      These studies indicate a possible autonomic dysregulation and hypersensitivity of
      the central nervous system in children with AP following stimulation with stress
      or other intense stimuli. Mainly conflicting results were found regarding
      baseline comparisons of autonomic and endocrine parameters. Conclusions and
      Inferences. Frequent AP in children may be associated with an altered
      psychophysiological reaction on intense stimuli. It has to be considered that the
      current literature on psychophysiological characteristics of childhood AP is
      small and heterogeneous. In particular, multiparameter studies using validated
      experimental paradigms are lacking. 

PMID- 24744779
TI  - A Parallel Framework for Multipoint Spiral Search in ab Initio Protein Structure
      Prediction.
AB  - Protein structure prediction is computationally a very challenging problem. A
      large number of existing search algorithms attempt to solve the problem by
      exploring possible structures and finding the one with the minimum free energy.
      However, these algorithms perform poorly on large sized proteins due to an
      astronomically wide search space. In this paper, we present a multipoint spiral
      search framework that uses parallel processing techniques to expedite exploration
      by starting from different points. In our approach, a set of random initial
      solutions are generated and distributed to different threads. We allow each
      thread to run for a predefined period of time. The improved solutions are stored
      threadwise. When the threads finish, the solutions are merged together and the
      duplicates are removed. A selected distinct set of solutions are then split to
      different threads again. In our ab initio protein structure prediction method, we
      use the three-dimensional face-centred-cubic lattice for structure-backbone
      mapping. We use both the low resolution hydrophobic-polar energy model and the
      high-resolution 20 * 20 energy model for search guiding. The experimental results
      show that our new parallel framework significantly improves the results obtained
      by the state-of-the-art single-point search approaches for both energy models on
      three-dimensional face-centred-cubic lattice. We also experimentally show the
      effectiveness of mixing energy models within parallel threads. 

PMID- 24744781
TI  - Appetite Response among Those Susceptible or Resistant to Obesity.
AB  - An alternative approach in determining cause, treatment, and prevention of
      obesity is to study those who appear resistant to the obesogenic environment. We
      examined appetite responses in 33 obesity resistant individuals (ORI) versus 28
      obesity susceptible individuals (OSI). Fingerprick blood samples to measure
      ghrelin, total peptide YY (PYY), leptin, glucose, and insulin along with appetite
      ratings were collected at baseline and 15, 30, 60, 120, and 180 min following
      consumption of a standardized meal. Fasting, area under the curve (AUC),
      peak/nadir, and time to peak/nadir were compared. Participants completed the
      three factor eating questionnaire (TFEQ). No significant differences were
      observed for ghrelin or PYY. Higher leptin concentrations in the OSI disappeared
      after controlling for percent body fat (%BF). Significant differences in appetite
      ratings included a lower hunger nadir among OSI compared with ORI (P = 0.017).
      Dietary restraint (P < 0.001) and disinhibition (P < 0.001) were lower in ORI
      compared with OSI, with and without adjustment for %BF. Given the differential
      body weight of the study groups, similar observed ghrelin concentrations were
      unexpected, perhaps indicating OSI and ORI respond differently to the same
      ghrelin concentration. Also ORI response to hunger appears different as they
      exhibit lower levels of dietary restraint and disinhibition compared with OSI. 

PMID- 24744780
TI  - Quality of Life and Sexual Health in the Aging of PCa Survivors.
AB  - Prostate cancer (PCa) is the most common malignancy in elderly men. The
      progressive ageing of the world male population will further increase the need
      for tailored assessment and treatment of PCa patients. The determinant role of
      androgens and sexual hormones for PCa growth and progression has been
      established. However, several trials on androgens and PCa are recently focused on
      urinary continence, quality of life, and sexual function, suggesting a new point
      of view on the whole endocrinological aspect of PCa. During aging, metabolic
      syndrome, including diabetes, hypertension, dyslipidemia, and central obesity,
      can be associated with a chronic, low-grade inflammation of the prostate and with
      changes in the sex steroid pathways. These factors may affect both the
      carcinogenesis processes and treatment outcomes of PCa. Any treatment for PCa can
      have a long-lasting negative impact on quality of life and sexual health, which
      should be assessed by validated self-reported questionnaires. In particular,
      sexual health, urinary continence, and bowel function can be worsened after
      prostatectomy, radiotherapy, or hormone treatment, mostly in the elderly
      population. In the present review we summarized the current knowledge on the role
      of hormones, metabolic features, and primary treatments for PCa on the quality of
      life and sexual health of elderly Pca survivors. 

PMID- 24744782
TI  - Energy Balance Regulating Neuropeptides Are Expressed through Pregnancy and
      Regulated by Interleukin-6 Deficiency in Mouse Placenta.
AB  - The placenta produces a number of signaling molecules including metabolic and
      reproductive hormones as well as several inflammatory mediators. Among them,
      Interleukin-6 (IL-6), a well-known immune and metabolic regulator, acts
      peripherally modulating metabolic function and centrally increasing energy
      expenditure and reducing body fat. IL-6 interacts with key hypothalamic
      neuropeptidergic systems controlling energy homeostasis such as those producing
      the orexigenic/anabolic: neuropeptide Y (NPY) and agouti-related peptide (AgRP)
      and anorectic/catabolic neuropeptides: proopiomelanocortin (POMC) and cocaine and
      amphetamine regulated transcript (CART). Human and rat placenta have been
      identified as source of these neuropeptides, but their expression and regulation
      in murine placental tissues remain unknown. Therefore, placental mRNA levels of
      IL-6, NPY, AgRP, POMC, and CART at different pregnancy stages (gestational days
      13, 15, and 18) were analyzed by real time PCR, as were the effect of IL-6
      deficiency (IL-6 knockout mice) on their placental expression. Our results showed
      that placenta-derived neuropeptides were regulated by gestational age and IL-6
      throughout the second half of mouse pregnancy. These data suggest that IL-6 may
      participate in the fine tune control of energy balance during pregnancy by
      extending its action as a metabolic signal to the main organ at the fetomaternal
      interface: the placenta. 

PMID- 24744783
TI  - The architecture of risk for type 2 diabetes: understanding Asia in the context
      of global findings.
AB  - The prevalence of Type 2 diabetes is rising rapidly in both developed and
      developing countries. Asia is developing as the epicentre of the escalating
      pandemic, reflecting rapid transitions in demography, migration, diet, and
      lifestyle patterns. The effective management of Type 2 diabetes in Asia may be
      complicated by differences in prevalence, risk factor profiles, genetic risk
      allele frequencies, and gene-environment interactions between different Asian
      countries, and between Asian and other continental populations. To reduce the
      worldwide burden of T2D, it will be important to understand the architecture of
      T2D susceptibility both within and between populations. This review will provide
      an overview of known genetic and nongenetic risk factors for T2D, placing the
      results from Asian studies in the context of broader global research. Given
      recent evidence from large-scale genetic studies of T2D, we place special
      emphasis on emerging knowledge about the genetic architecture of T2D and the
      potential contribution of genetic effects to population differences in risk. 

PMID- 24744784
TI  - Activation of toll-like receptors and inflammasome complexes in the diabetic
      cardiomyopathy-associated inflammation.
AB  - Diabetic cardiomyopathy is defined as a ventricular dysfunction initiated by
      alterations in cardiac energy substrates in the absence of coronary artery
      disease and hypertension. Hyperglycemia, hyperlipidemia, and insulin resistance
      are major inducers of the chronic low-grade inflammatory state that characterizes
      the diabetic heart. Cardiac Toll-like receptors and inflammasome complexes may be
      key inducers for inflammation probably through NF-kappaB activation and ROS
      overproduction. However, metabolic dysregulated factors such as peroxisome
      proliferator-activated receptors and sirtuins may serve as therapeutic targets to
      control this response by mitigating both Toll-like receptors and inflammasome
      signaling. 

PMID- 24744786
TI  - Characterization of the Protective HIV-1 CTL Epitopes and the Corresponding HLA
      Class I Alleles: A Step towards Designing CTL Based HIV-1 Vaccine.
AB  - Human immunodeficiency virus (HIV) possesses a major threat to the human life
      largely due to the unavailability of an efficacious vaccine and poor access to
      the antiretroviral drugs against this deadly virus. High mutation rate in the
      viral genome underlying the antigenic variability of the viral proteome is the
      major hindrance as far as the antibody based vaccine development is concerned.
      Although the exact mechanism by which CTL epitopes and the restricting HLA
      alleles mediate their action towards slow disease progression is still not clear,
      the important CTL restricted epitopes for controlling viral infections can be
      utilized in future vaccine design. This study was designed for the
      characterization the HIV-1 optimal CTL epitopes and their corresponding HLA
      alleles. CTL epitope cluster distribution analysis revealed only two HIV-1
      proteins, namely, Nef and Gag, which have significant cluster forming capacity.
      We have found the role of specific HLA supertypes such as HLA B*07, HLA B*58, and
      HLA A*03 in selecting the hydrophobic and conserved amino acid positions within
      Nef and Gag proteins, to be presented as epitopes. The analyses revealed that the
      clusters of optimal epitopes for Nef and p24 proteins of HIV-1 could potentially
      serve as a source of vaccine. 

PMID- 24744785
TI  - Erectile dysfunction in the elderly: an old widespread issue with novel treatment
      perspectives.
AB  - Erectile dysfunction (ED) is one of the most common chronic diseases affecting
      men and its prevalence increases with aging. It is also the most frequently
      diagnosed sexual dysfunction in the older male population. A number of different
      diseases potentially worsening sexual function may occur in elderly people,
      together with polypharmacy. Related causes of ED are variable and can include
      arterial, neurogenic, hormonal, cavernosal, iatrogenic, and psychogenic causes.
      The aim of the present review was to examine the main aspects of erectile
      dysfunction going through epidemiology and pathophysiology and revise most of ED
      in elderly disabled men and in those affected with psychiatric disorders. Lastly
      we tried to focus on the main aspects of nonpharmacological and pharmacological
      treatments of ED and the recreational use in the elderly. Phosphodiesterase-5
      inhibitors (PDE5-I) are commonly used for on-demand or chronic treatment of ED.
      It is widely known that PDE5-I have lower response rates in older men than in
      younger patients, but they have the advantages of ease of use and excellent
      safety profile, also in the elderly. The old and new PDE5-I as well as the
      alternative treatments for ED are extensively discussed. 

PMID- 24744787
TI  - Secondary Acute Myeloid Leukemia in a One-Year-Old Girl Diagnosed with JAK2-V617F
      Mutation Positive Myeloproliferative Neoplasm.
AB  - Myeloproliferative neoplasms (MPNs) are a group of clonal disorders characterized
      by hyperproliferation of hematologic cell lines and have been associated with
      tyrosine kinase JAK2-V617F mutations. Secondary acute myeloid leukemia (sAML) is
      a known complication of JAK2-V617F+ MPNs and bears a poor prognosis. Although the
      evolution of a JAK2-V617F+ MPN to a mixed-lineage leukemia has been reported in
      the pediatric population, no evolutions into sAML have been described. We present
      a case of a one-year-old girl diagnosed with JAK2-V617F+ MPN with evolution into
      sAML. Despite initial morphologic remission, she eventually relapsed and
      succumbed to her disease. 

PMID- 24744789
TI  - Evaluation of trace metal content by ICP-MS using closed vessel microwave
      digestion in fresh water fish.
AB  - The objective of the present study was to investigate trace metal levels of
      different varieties of fresh water fish using Inductively Coupled Plasma Mass
      Spectrophotometer after microwave digestion (MD-ICPMS). Fish samples were
      collected from the outlets of twin cities of Hyderabad and Secunderabad. The
      trace metal content in different varieties of analyzed fish were ranged from 0.24
      to 1.68 mg/kg for Chromium in Cyprinus carpio and Masto symbollon, 0.20 to 7.52
      mg/kg for Manganese in Labeo rohita and Masto symbollon, 0.006 to 0.07 mg/kg for
      Cobalt in Rastrelliger kanagurta and Pampus argenteus, 0.31 to 2.24 mg/kg for
      Copper in Labeo rohita and Penaeus monodon, 3.25 to 14.56 mg/kg for Zinc in
      Cyprinus carpio and Macrobrachium rosenbergii, and 0.01 to 2.05 mg/kg for
      Selenium in Rastrelliger kanagurta and Pampus argenteus, respectively. Proximate
      composition data for the different fishes were also tabulated. Since the
      available data for different trace elements for fish is scanty, here an effort is
      made to present a precise data for the same as estimated on ICP-MS. Results were
      in accordance with recommended daily intake allowance by WHO/FAO. 

PMID- 24744788
TI  - Concomitant Infection with Leishmania donovani and L. major in Single Ulcers of
      Cutaneous Leishmaniasis Patients from Sudan.
AB  - In Sudan human leishmaniasis occurs in different clinical forms, that is,
      visceral (VL), cutaneous (CL), mucocutaneous (ML), and post-kala-azar dermal
      leishmaniasis (PKDL). Clinical samples from 69 Sudanese patients with different
      clinical manifestations were subjected to a PCR targeting the cytochrome oxidase
      II (COII) gene for Leishmania species identification. Mixed infections were
      suspected due to multiple overlapping peaks presented in some sequences of the
      COII amplicons. Cloning these amplicons and alignment of sequences from randomly
      selected clones confirmed the presence of two different Leishmania species, L.
      donovani and L. major, in three out of five CL patients. Findings were further
      confirmed by cloning the ITS gene. Regarding other samples no significant genetic
      variations were found in patients with VL (62 patients), PKDL (one patient), or
      ML (one patient). The sequences clustered in a single homogeneous group within L.
      donovani genetic group, with the exception of one sequence clustering with L.
      infantum genetic group. Findings of this study open discussion on the
      synergetic/antagonistic interaction between divergent Leishmania species both in
      mammalian and vector hosts, their clinical implications with respect to parasite
      fitness and response to treatment, and the route of transmission with respect to
      vector distribution and or adaptation. 

PMID- 24744790
TI  - Interferon alpha-2b therapy in chronic hepatitis delta.
AB  - BACKGROUND: Approximately 5% of hepatitis B virus (HBV) carriers are coinfected
      with hepatitis D virus (HDV). HBV/HDV coinfection is a major cause of cirrhosis
      and end stage liver disease in chronic HBsAg carriers. The only approved therapy
      for chronic hepatitis delta is interferon alpha (IFN alpha) in either pegylated
      or conventional forms. Although higher doses and longer durations of IFN alpha
      therapy in HBV/HDV coinfected patients are currently applied, yet treatment
      response is low. OBJECTIVES: We aimed to determine the efficacy of IFN alpha-2b
      therapy in patients with HBV/HDV coinfection. PATIENTS AND METHODS: In this cross
      sectional study, 20 HBsAg carriers with positive Anti-HDVAb and RT-PCR for HDV
      RNA were recruited and treated for three year duration with 5 million units (MU)
      of IFN alpha-2b, three times weekly or one year with 5 MU of IFN alpha-2b daily.
      Sustained virological response (SVR) was defined as a negative qualitative HDV RT
      PCR, 6 months after treatment cessation. RESULTS: Overall, 3 (15%) subjects
      achieved SVR, 10 cases (50%) relapsed after treatment cessation and 7 (35%)
      patients did not clear HDV during the treatment. CONCLUSIONS: HDV coinfection
      with HBV had very low response rate to high doses and long durations of IFN alpha
      2b therapy.

PMID- 24744791
TI  - Patterns and Biologic Features of p53 Mutation Types in Korean Breast Cancer
      Patients.
AB  - PURPOSE: The p53 gene is one of the most frequently mutated genes in breast
      cancer. We investigated the patterns and biologic features of p53 gene mutation
      and evaluated their clinical significance in Korean breast cancer patients.
      METHODS: Patients who underwent p53 gene sequencing were included. Mutational
      analysis of exon 5 to exon 9 of the p53 gene was carried out using polymerase
      chain reaction-denaturing high performance liquid chromatography and direct
      sequencing. RESULTS: A total of 497 patients were eligible for the present study
      and p53 gene mutations were detected in 71 cases (14.3%). Mutation of p53 was
      significantly associated with histologic grading (p<0.001), estrogen receptor and
      progesterone receptor status (p<0.001), HER2 status (p<0.001), Ki-67 (p=0.028),
      and tumor size (p=0.004). The most frequent location of p53 mutations was exon 7
      and missense mutation was the most common type of mutation. Compared with
      patients without mutation, there was a statistically significant difference in
      relapse-free survival of patients with p53 gene mutation and missense mutation
      (p=0.020, p=0.006, respectively). Only p53 missense mutation was an independent
      prognostic factor for relapse-free survival in multivariate analysis, with an
      adjusted hazard ratio of 2.29 (95% confidence interval, 1.08-4.89, p=0.031).
      CONCLUSION: Mutation of the p53 gene was associated with more aggressive
      clinicopathologic characteristics and p53 missense mutation was an independent
      negative prognostic factor in Korean breast cancer patients.

PMID- 24744792
TI  - Zonal difference and prognostic significance of foxp3 regulatory T cell
      infiltration in breast cancer.
AB  - PURPOSE: Forkhead box P3 (Foxp3) is known as the most specific marker for
      regulatory T lymphocytes, which play an important role in immune tolerance to
      disturb antitumor immunity. The present study aimed to investigate the prognostic
      significance of Foxp3 regulatory T lymphocyte (Foxp3 Treg) infiltration in breast
      cancer. METHODS: Immunohistochemical studies with Foxp3, CD4, and CD8 were
      performed on representative full tissue sections from 143 patients with invasive
      ductal carcinoma, not otherwise specified. Foxp3 Treg infiltration and the ratios
      between Foxp3 Treg and CD4 or CD8 T cells were separately analyzed for the tumor
      bed and tumor periphery to evaluate their association with different
      clinicopathological parameters and patients' outcome. RESULTS: The tumor
      periphery was considerably more densely infiltrated by Foxp3 Treg, CD4, and CD8 T
      cells than the tumor bed. Unfavorable clinicopathological parameters (a Ki-67
      labeling index of >=14%, a worse histologic grade, a worse nuclear grade, hormone
      receptor negativity, human epidermal growth factor receptor 2 positivity, and
      tumor recurrence) were associated with increased Foxp3 Treg infiltration and a
      high ratio between Foxp3 Treg and CD4/CD8 T cells. In the tumor periphery, as
      Foxp3 Treg infiltration and the Foxp3 Treg/CD8 ratio increased, patients' 5-year
      disease-free survival rate decreased. CONCLUSION: The infiltration densities of
      Foxp3 Treg, CD4, and CD8 T cells were markedly different between the tumor bed
      and periphery. Besides the absolute count of Foxp3 Treg, the ratio between Foxp3
      Treg and effector T cells was a significant prognostic factor in breast cancer.

PMID- 24744793
TI  - Microgel-encapsulated methylene blue for the treatment of breast cancer cells by
      photodynamic therapy.
AB  - PURPOSE: Photodynamic therapy (PDT) is gaining increasing recognition for breast
      cancer treatment because it offers local selectivity and reduced toxic side
      effects compared to radiotherapy and chemotherapy. In PDT, photosensitizer drugs
      are loaded in different nanomaterials and used in combination with light
      exposure. However, the most representative issue with PDT is the difficulty of
      nanomaterials to encapsulate anticancer drugs at high doses, which results in low
      efficacy of the PDT treatment. Here, we proposed the development of the poly(N
      isopropylacrylamide) (PNIPAM) microgel for the encapsulation of methylene blue,
      an anticancer drug, for its use as breast cancer treatment in MCF-7 cell line.
      METHODS: We developed biocompatible microgels based on nonfunctionalized PNIPAM
      and its corresponding anionically functionalized PNIPAM and polyacrylic acid
      (PNIPAM-co-PAA) microgel. Methylene blue was used as the photosensitizer drug
      because of its ability to generate toxic reactive oxygen species upon exposure to
      light at 664 nm. Core PNIPAM and core/shell PNIPAM-co-PAA microgels were
      synthesized and characterized using ultraviolet-visible spectroscopy and dynamic
      light scattering. The effect of methylene blue was evaluated using the MCF-7 cell
      line. RESULTS: Loading of methylene blue in core PNIPAM microgel was higher than
      that in the core/shell PNIPAM-co-PAA microgel, indicating that electrostatic
      interactions did not play an important role in loading a cationic drug. This
      behavior is probably due to the skin layer inhibiting the high uptake of drugs in
      the PNIPAM-co-PAA microgel. Core PNIPAM microgel effectively retained the
      cationic drug (i.e., methylene blue) for several hours compared to core/shell
      PNIPAM-co-PAA and enhanced its photodynamic efficacy in vitro more than that of
      free methylene blue. CONCLUSION: Our results showed that the employment of core
      PNIPAM and core/shell PNIPAM-co-PAA microgels enhanced the encapsulation of
      methylene blue. Core PNIPAM microgel released the drug more slowly than did
      core/shell PNIPAM-co-PAA, and it effectively inhibited the growth of MCF-7 cells.

PMID- 24744794
TI  - Dimethyl Sulfoxide Suppresses Mouse 4T1 Breast Cancer Growth by Modulating Tumor
      Associated Macrophage Differentiation.
AB  - PURPOSE: The universal organic solvent dimethyl sulfoxide (DMSO) can be used as a
      differentiation inducer of many cancer cells and has been widely used as a
      solvent in laboratories. However, its effects on breast cancer cells are not well
      understood. The aim of this study is to investigate the effect and associated
      mechanisms of DMSO on mouse breast cancer. METHODS: We applied DMSO to observe
      the effect on tumors in a mouse breast cancer model. Tumor-associated macrophages
      (TAMs) were tested by flow cytometry. Ex vivo tumor microenvironment was imitated
      by 4T1 cultured cell conditioned medium. Enzyme-linked immunosorbent assays were
      performed to detect interleukin (IL)-10 and IL-12 expression in medium. To
      investigate the cytotoxicity of DMSO on TAMs, 3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide (MTT) assays were performed. RESULTS: We found that
      DMSO produced tumor retardation when injected into mouse peritoneal cavities in a
      certain concentration range (0.5-1.0 mg/g). Furthermore, as detected by flow
      cytometry, TAM subtypes were found to be transformed. We further imitated a tumor
      microenvironment in vitro by using 4T1 cultured cell conditioned medium.
      Similarly, by using low concentration DMSO (1.0%-2.0% v/v), TAMs were induced to
      polarize to the classically activated macrophage (M1-type) and inhibited from
      polarizing into the alternatively activated macrophage (M2-type) in the
      conditioned medium. IL-10 expression in tumors was reduced, while IL-12 was
      increased compared with the control. Furthermore, we reported that 2.0% (v/v)
      DMSO could lead to cytotoxicity in peritoneal macrophages after 48 hours in MTT
      assays. CONCLUSION: Our findings suggest that DMSO could exert antitumor effects
      in 4T1 cancer-bearing mice by reversing TAM orientation and polarization from M2-
      to M1-type TAMs. These data may provide novel insight into studying breast cancer
      immunotherapy.

PMID- 24744796
TI  - Ki-67 as a predictor of response to neoadjuvant chemotherapy in breast cancer
      patients.
AB  - PURPOSE: The objectives of this study were to assess the potential value of Ki-67
      in predicting response to neoadjuvant chemotherapy in breast cancer patients and
      to suggest a reasonable cutoff value for classifying Ki-67 expression. METHODS:
      This study included 74 breast cancer patients who underwent surgery after
      anthracycline-based neoadjuvant chemotherapy between 2007 and 2012. We analyzed
      the clinical and immunohistochemical characteristics using core biopsy specimens
      obtained before neoadjuvant chemotherapy to determine their correlations with the
      response to chemotherapy. RESULTS: A clinical complete response was observed in 6
      patients (8.1%); a clinical partial response, in 44 patients (59.5%); and
      clinical stable disease, in 24 patients (32.4%). A pathologic complete response
      (pCR) was observed in 10 patients (13.5%). In univariate analysis, estrogen
      receptor (ER) negativity (p=0.031), human epidermal growth factor receptor 2
      (HER2) positivity (p=0.040), and high Ki-67 expression (p=0.036) were predictive
      factors for a pCR. In multivariate analysis, Ki-67 was the only independent
      predictor of a pCR (p=0.049). The analysis of Ki-67 values revealed that 25% was
      a reasonable cutoff value for predicting the response to chemotherapy. In
      subgroup analysis, a higher Ki-67 value (>=25%) was a significant predictive
      factor for the response to neoadjuvant chemotherapy, especially in ER-negative
      and HER2-positive breast cancer patients. CONCLUSION: Ki-67 expression in breast
      cancer tissue may be an effective factor for predicting the response to
      neoadjuvant chemotherapy. We suggest that a 25% level of Ki-67 expression is a
      reasonable cutoff value for predicting a response to chemotherapy. Moreover, Ki
      67 is a useful predictive factor for pCR, especially in patients with ER-negative
      and HER2-positive breast cancer.

PMID- 24744795
TI  - Serial Serum HER2 Measurements for the Detection of Breast Cancer Recurrence in
      HER2-Positive Patients.
AB  - PURPOSE: The measurement of serum human epidermal growth factor receptor 2 (HER2)
      extracellular domain levels is a well-established method for evaluating whether a
      metastatic HER2-positive breast cancer patient will respond to HER2-targeted
      treatment. However, little is known about the value of serum HER2 for detecting
      disease relapse following curative surgical treatment in breast cancer patients.
      The purpose of this study was to evaluate the sensitivity of serum HER2,
      carcinoembryonic antigen (CEA), and carcinoma antigen 15-3 (CA 15-3) for the
      detection of disease recurrence in postoperative breast cancer patients with a
      primary HER2-positive tumor. METHODS: Serial measurements were taken of serum
      HER2, CEA, and CA 15-3 levels in patients with primary invasive HER2-positive
      breast cancer who underwent curative surgical treatment between January 2008 and
      December 2010. Following treatment, serum HER2 levels were monitored every 6
      months using a chemiluminescence immunoassay. RESULTS: Overall, 264 patients were
      analyzed in this retrospective study. The median follow-up period was 27.7
      months, and 24 patients relapsed during follow-up. The sensitivity of serum HER2,
      CEA, and CA 15-3 for the detection of disease recurrence was 37.5%, 25.1%, and
      12.5%, respectively. Sensitivity increased to 45.8% when all three tumor markers
      were combined in the analysis. In a subgroup of patients without liver disease,
      the sensitivity of serum HER2, CEA, and CA 15-3 was 57.1%, 21.4%, and 14.3%,
      respectively. Of the 264 patients in this study, 80 patients had chronic
      hepatitis, liver cirrhosis, or abnormal aspartate aminotransferase or alanine
      aminotransferase levels during the follow-up period. Following the exclusion of
      these patients, the sensitivity of serum HER2 for the detection of disease
      recurrence increased to 57.1%. CONCLUSION: Serial serum HER2 measurement may be
      useful for the detection of disease relapse in patients with HER2-positive breast
      cancer. Abnormal liver function can result in elevated serum HER2 in the absence
      of disease recurrence.

PMID- 24744797
TI  - Longer survival in patients with breast cancer with cyclin d1 over-expression
      after tumor recurrence: longer, but occupied with disease.
AB  - PURPOSE: The effect of cyclin D1 overexpression on breast cancer outcomes and
      prognosis is controversial, even though amplification of the cyclin D1 gene,
      CCND1, has been shown to be associated with early relapse and poor prognosis. In
      this study, we examined the relationship between cyclin D1 overexpression and
      disease-specific survival (DSS). We also analyzed survival in patients who
      experienced recurrence. METHODS: We retrospectively analyzed data from patients
      diagnosed with ductal carcinoma between April 2005 and December 2010. We examined
      clinicopathologic factors associated with cyclin D1 overexpression and analyzed
      the influence of cyclin D1 on recurrence-free survival and DSS. RESULTS: We
      identified 236 patients diagnosed with primary breast cancer who completed all
      phases of their primary treatment. Cyclin D1 overexpression was significantly
      associated with longer DSS (5-year DSS, 89.9% in patients without cyclin D1
      overexpression vs. 98.9% in patients with cyclin D1 overexpression; p=0.008).
      Multivariate analysis also found that patients with cyclin D1 overexpressing
      tumors had significantly longer disease-specific survival than patients whose
      tumors did not overexpress cyclin D1, with a hazard ratio for disease-specific
      mortality of 7.97 (1.17-54.22, p=0.034). However, in the group of patients who
      experienced recurrence, cyclin D1 overexpression was not significantly associated
      with recurrence-free survival. Cyclin D1 overexpression was significantly
      associated with increased survival after disease recurrence, indicating that
      cyclin D1 overexpression might be indicative of more indolent disease progression
      after metastasis. CONCLUSION: Cyclin D1 overexpression is associated with longer
      DSS, but not recurrence-free survival, in patients with breast cancer. Longer
      postrecurrence survival could explain the apparent inconsistency between DSS and
      recurrence-free survival. Patients with cyclin D1-overexpressing tumors survive
      longer, but with metastatic disease after recurrence. This information should
      spark the urgent development of tailored therapies to cure these patients.

PMID- 24744798
TI  - The expression of aldehyde dehydrogenase family in breast cancer.
AB  - PURPOSE: It is widely accepted that aldehyde dehydrogenase (ALDH) activity is a
      signature of breast cancer stem cells, and high activity has been reported to be
      associated with poor clinical outcome. The aim of this study was to assess the
      expression of members of the ALDH family of isozymes in breast cancer tissues and
      to evaluate the implications of the results. METHODS: We analyzed paraffin
      embedded tumor tissue from 160 patients with breast cancer. Immunohistochemistry
      (IHC) staining was performed on the slides using antibodies against different
      ALDH family members. We collated the IHC results with patient clinical
      characteristics and determined their prognostic value. In addition, we analyzed
      normal, hyperplastic, and carcinomatous tissues in situ to check their ALDH
      distributions. RESULTS: All the tested ALDH members were detected in the various
      tissue types, but at different levels. Only ALDH 1A3 was found to be
      significantly associated with distant metastasis (p=0.001), disease-free survival
      (p<0.001), and overall survival (p<0.001). CONCLUSION: The level of ALDH 1A3 in
      breast cancer tissue is a predictive marker of a poor clinical outcome.

PMID- 24744799
TI  - Efficacy and Safety Profile of Combining Sorafenib with Chemotherapy in Patients
      with HER2-Negative Advanced Breast Cancer: A Meta-analysis.
AB  - PURPOSE: The aim of the study was to evaluate the efficacy and safety of
      combining sorafenib with chemotherapy in patients with human epidermal growth
      factor receptor 2 (HER2)-negative advanced breast cancer. METHODS: MEDLINE,
      EMBASE, Cochrane Central Register of Controlled Trials, American Society for
      Clinical Oncology abstracts, and European Society for Medical Oncology abstracts
      were searched. Randomized clinical trials that compared the efficacy and safety
      of sorafenib plus chemotherapy in patients with HER2-negative advanced breast
      cancer with placebo plus chemotherapy were eligible. The endpoints were
      progression-free survival (PFS), overall survival (OS), time to progression
      (TTP), duration of response (DOR), overall response rate (ORR), clinical
      benefits, and adverse effects. The meta-analysis was performed using Review
      Manager 5.2.6 (The Nordic Cochrane Centre), and the fixed-effect model weighted
      by the Mantel-Haenszel method was used. When considerable heterogeneity was found
      (p<0.1), further analysis (subgroup analysis, sensitivity analysis, or random
      effect model) was performed to identify the potential cause. The results are
      expressed as hazard ratios or risk ratios, with their corresponding 95%
      confidence intervals. RESULTS: The final analysis included four trials comprising
      844 patients. The results revealed longer PFS and TTP, and higher ORR and
      clinical benefit rates in patients receiving sorafenib combined with chemotherapy
      compared to those receiving chemotherapy and placebo. OS and DOR were similar in
      the two groups. Meanwhile, the incidence of some adverse effects, including hand
      foot skin reaction/hand-foot syndrome, diarrhea, rash, and hypertension, were
      significantly higher in the sorafenib arm. CONCLUSION: Sorafenib combined with
      chemotherapy may prolong PFS and TTP. This treatment was associated with
      manageable toxicities, but frequent dose interruptions and reductions were
      required.

PMID- 24744800
TI  - Analysis of predictive factors for lung injury after forward-planned intensity
      modulated radiotherapy in whole breast irradiation.
AB  - PURPOSE: This study was performed to assess frequency, timings of occurrence, and
      predictors of radiologic lung damage (RLD) after forward-planned intensity
      modulated radiotherapy (FIMRT) for whole breast irradiation. METHODS: We
      retrospectively reviewed medical records of 157 breast cancer patients and each
      of their serial chest computed tomography (CT) taken 4, 10, 16, and 22 months
      after completion of breast radiotherapy (RT). FIMRT was administered to whole
      breast only (n=152), or whole breast and supraclavicular regions (n=5).
      Dosimetric parameters, such as mean lung dose and lung volume receiving more than
      10 to 50 Gy (V10-V50), and clinical parameters were analyzed in relation to
      radiologic lung damage. RESULTS: In total, 104 patients (66.2%) developed RLD
      after whole breast FIMRT. Among the cases of RLD, 84.7% were detected at 4
      months, and 15.3% at 10 months after completion of RT. More patients of 47 or
      younger were found to have RLD at 10 months after RT than patients older than the
      age (11.7% vs. 2.9%, p=0.01). In univariate and multivariate analyses, age >47
      and V40 >7.2% were significant predictors for higher risk of RLD. CONCLUSION: RLD
      were not infrequently detected in follow-up CT after whole breast FIMRT. More
      detected cases of RLD among younger patients are believed to have developed at
      later points after RT than those of older patients. Age and V40 were significant
      predictors for RLD after whole breast intensity-modulated radiotherapy.

PMID- 24744801
TI  - Diagnostic value of elastography using acoustic radiation force impulse imaging
      and strain ratio for breast tumors.
AB  - PURPOSE: The aim of this study was to determine whether the combination of B-mode
      ultrasonography (BUS), acoustic radiation force impulse (ARFI) elastography, and
      strain ratio (SR) provides better diagnostic performance of breast lesion
      differentiation than BUS alone. METHODS: ARFI elastography and SR evaluations
      were performed on patients with 157 breast lesions diagnosed by BUS from June to
      September 2013. BUS images were classified according to the Breast Imaging
      Reporting and Data System. ARFI elastography was performed using Virtual TouchTM
      tissue imaging (VTI) and Virtual TouchTM tissue quantification (VTQ). In VTI
      mode, we evaluated the color-mapped patterns of the breast lesion and surrounding
      tissue. The lesions were classified into five categories by elasticity score. In
      VTQ mode, each lesion was assessed using shear wave velocity (SWV) measurements.
      SR was calculated from the lesion and comparable lateral fatty tissue. We
      compared the diagnostic performance of BUS alone and the combination of BUS, ARFI
      elastography, and SR evaluations. RESULTS: Among the 157 lesions, 40 were
      malignant and 117 were benign. The mean elasticity score (3.7+/-1.0 vs. 1.6+/
      0.8, p<0.01), SWV (4.23+/-1.09 m/sec vs. 2.22+/-0.88 m/sec, p<0.01), and SR
      (5.69+/-1.63 vs. 2.69+/-1.40, p<0.01) were significantly higher for malignant
      lesions than benign lesions. The results for BUS combined with ARFI elastography
      and SR values were 97.5% sensitivity, 92.3% specificity, 93.6% accuracy, a 79.6%
      positive predictive value (PPV), and a 99.1% negative predictive value. The
      combination of the 3 radiologic examinations yielded superior specificity,
      accuracy, and PPV compared to BUS alone (p<0.01 for each). CONCLUSION: ARFI
      elastography and SR evaluations showed significantly different mean values for
      benign and malignant lesions. Moreover, these two modalities complemented BUS and
      improved the diagnostic performance of breast lesion detection. Therefore, ARFI
      elastography and SR evaluations can be used as complementary modalities to make
      more accurate breast lesion diagnoses.

PMID- 24744803
TI  - Metastatic breast cancer presenting as a subconjunctival mass.
AB  - Breast cancer is the most common primary source of orbital metastasis. Metastasis
      occurs through hematogenous spread and predominantly involves the choroid. We
      present a case of a metastatic subconjunctival mass associated with primary
      breast cancer. To our knowledge, this is the first reported case of its kind. A
      41-year-old woman presented with complaints of conjunctival injection and a
      foreign body sensation in the left eye. She had a history of breast cancer and
      had been treated 2 years previously with modified radical mastectomy followed by
      adjuvant radiotherapy and chemotherapy. Slit-lamp examination showed a cystic
      mass under the temporal bulbar conjunctiva, associated with dilated overlying
      conjunctival vessels. An excisional biopsy revealed a poorly differentiated
      adenocarcinoma. Positron emission tomography examination for systemic malignancy
      revealed multiple systemic metastasis. Metastatic disease should be considered in
      the differential diagnosis of subconjunctival lesions, and ophthalmic
      manifestations can play an important role in the detection of metastatic spread
      of a known primary breast cancer. 

PMID- 24744802
TI  - Polyostotic fibrous dysplasia mimicking multiple bone metastases in a patient
      with ductal carcinoma in situ.
AB  - Whole-body bone scans and whole body (18)F-fluorodeoxyglucose positron emission
      tomographic/computed tomographic scans are sensitive for detecting bone
      metastasis in patients with breast cancer. However, it is often difficult to
      discriminate between bone metastasis and other nonmalignant bone lesions.
      Polyostotic fibrous dysplasia is a rare disorder characterized by the osteoid
      medullary cavity filling with fibrous tissue causing bony expansion. We report
      the case of a 42-year-old female patient with ductal carcinoma in situ, which
      appeared to have multiple bone metastases on initial work-up images.
      Subsequently, the bone metastases were identified as polyostotic fibrous
      dysplasia. The patient underwent modified radical mastectomy and subsequently
      visited for a second opinion regarding the bony metastases. She underwent right
      ilium computed tomography-guided biopsy. Pathology was consistent with fibrous
      dysplasia. This patient received only adjuvant tamoxifen, and 1.5 years later,
      there was no evidence of recurrence. 

PMID- 24744804
TI  - Concurrent invasive ductal carcinoma of the breast and malignant follicular
      lymphoma, initially suspected to be metastatic breast cancer: a case report.
AB  - This report describes a case of a 40-year-old female patient with concurrent
      invasive ductal carcinoma of the breast and malignant follicular lymphoma,
      initially suspected to be metastatic breast cancer. During the initial evaluation
      of invasive ductal carcinoma of right breast, multiple lymphadenopathies were
      noted throughout the body on ultrasonography and positron emission
      tomography/computed tomography images. Clinically, metastatic breast cancer was
      suggested, and the patient was administered chemotherapy, including hormonal
      therapy. The breast cancer improved slightly, but the lymphadenopathies
      progressed and excisional biopsy of a cervical lymph node revealed malignant
      follicular lymphoma. 

PMID- 24744805
TI  - The non-anticoagulation costs of atrial fibrillation management: findings from an
      observational study in NHS Primary Care.
AB  - BACKGROUND: Atrial fibrillation (AF) management represents a significant burden
      on the UK NHS. Understanding this burden will be important in informing future
      health care planning and policy development. AIM: To describe the non
      anticoagulation costs associated with AF management in routine UK clinical
      practice. MATERIALS PATIENTS AND METHODS: A retrospective observational study of
      825 patients with AF undertaken in eight UK primary care practices. Data
      collected from routine clinical and prescribing records of all eligible,
      consenting patients, for a period of up to 3 years. The first 12 weeks following
      diagnosis was defined as the 'initiation phase'; the period after week 12 was
      defined as the 'maintenance phase'. RESULTS: Mean (SD) total cost of AF
      management was L941 (L1094) per patient in the initiation phase and L426 (L597)
      per patient-year in the maintenance phase. AF-related inpatient admissions
      contributed most to total costs; the mean (SD) total cost per patient in the
      initiation phase was L2285 (L900) for admitted and L278 (L252) for non-admitted
      patients. Mean maintenance phase costs per year were L1323 (L755) and L168
      (L234), respectively, for admitted and non-admitted patients. Significant patient
      variables contributing to high cost in the initiation phase were hypertension and
      younger patient age, although only accounting for 6% of cost variability.
      Significant variables in the maintenance phase (18% of cost variability) were the
      presence of congestive heart failure, structural heart disease or diabetes and
      the frequency of day case admissions, ECGs and hospitalisations in the initiation
      phase. CONCLUSIONS: Inpatient admissions contributed most to total AF management
      costs. Given the burden of hospital care, future work should focus on evaluating
      the appropriateness and reasons for hospitalisation in patients with AF and the
      factors affecting length of stay, with the aim of identifying opportunities to
      safely reduce inpatient costs. A number of significant patient characteristics
      and initiation phase variables were identified, which accounted for 18% of the
      variability in total maintenance phase costs. However, none of these could
      adequately predict high maintenance phase costs.

PMID- 24744807
TI  - Effectiveness of Stimulation of Acupoint KI 1 by Artemisia vulgaris (Moxa) for
      the Treatment of Essential Hypertension: A Systematic Review of Randomized
      Controlled Trials.
AB  - Objective. A systematic review of randomized controlled trials has been performed
      to assess the effectiveness of stimulation of acupoint KI 1 by Artemisia vulgaris
      (the Japanese name is moxa) to lower blood pressure compared to antihypertensive
      drugs. Methods and Findings. Articles published from 1980 to August 2013 in
      databases of CENTRAL, Pubmed, CBM, CNKI, VIP, and online clinical trial registry
      websites were searched. Studies included were randomized controlled trials
      (RCTs); moxibustion-type intervention on KI 1 compared with antihypertensive
      drugs; meta-analysis showed superior effects of moxibustion plus antihypertensive
      drugs on systolic blood pressure (WMD: -4.91 [-7.54, -2.28]; P = 0.0003) but no
      superior effects on diastolic blood pressure (WMD: -6.38 [-17.17, 4.41]; P =
      0.25). Conclusions. Our systematic review of the current literature shows a
      beneficial effect of using moxibustion interventions on KI 1 to lower blood
      pressure compared to antihypertensive drugs. However, the results are influenced
      by the existing differences in design of the current trials. 

PMID- 24744806
TI  - Tardive dyskinesia in patients treated with atypical antipsychotics: case series
      and brief review of etiologic and treatment considerations.
AB  - Tardive dyskinesia (TD) is a disfiguring side-effect of antipsychotic medications
      that is potentially irreversible in affected patients. Newer atypical
      antipsychotics are felt by many to have a lower risk of TD. As a result, many
      clinicians may have developed a false sense of security when prescribing these
      medications. We report five cases of patients taking atypical antipsychotics who
      developed TD, review the risk of TD, its potential etiologic mechanisms, and
      treatment options available. The goal of this paper is to alert the reader to
      continue to be diligent in obtaining informed consent and monitoring for the
      onset of TD in patients taking atypical antipsychotics. 

PMID- 24744808
TI  - Text mining of the classical medical literature for medicines that show potential
      in diabetic nephropathy.
AB  - Objectives. To apply modern text-mining methods to identify candidate herbs and
      formulae for the treatment of diabetic nephropathy. Methods. The method we
      developed includes three steps: (1) identification of candidate ancient terms;
      (2) systemic search and assessment of medical records written in classical
      Chinese; (3) preliminary evaluation of the effect and safety of candidates.
      Results. Ancient terms Xia Xiao, Shen Xiao, and Xiao Shen were determined as the
      most likely to correspond with diabetic nephropathy and used in text mining. A
      total of 80 Chinese formulae for treating conditions congruent with diabetic
      nephropathy recorded in medical books from Tang Dynasty to Qing Dynasty were
      collected. Sao si tang (also called Reeling Silk Decoction) was chosen to show
      the process of preliminary evaluation of the candidates. It had promising
      potential for development as new agent for the treatment of diabetic nephropathy.
      However, further investigations about the safety to patients with renal
      insufficiency are still needed. Conclusions. The methods developed in this study
      offer a targeted approach to identifying traditional herbs and/or formulae as
      candidates for further investigation in the search for new drugs for modern
      disease. However, more effort is still required to improve our techniques,
      especially with regard to compound formulae. 

PMID- 24744809
TI  - Intracellular ROS Scavenging Activity and Downregulation of Inflammatory
      Mediators in RAW264.7 Macrophage by Fresh Leaf Extracts of Pseuderanthemum
      palatiferum.
AB  - Beneficial antioxidant phytochemicals are found in many medicinal plants.
      Pseuderanthemum palatiferum (PP), a well-known Vietnamese traditional medicinal
      plant in Thailand, has long been used in folk medicine for curing inflammatory
      diseases, often with limited support of scientific research. Therefore, this
      study aimed to determine antioxidant and modulation of inflammatory mediators of
      ethanol and water extracts of PP (EEP and WEP, resp.). WEP had significantly
      higher phenolic and flavonoid levels and DPPH radical scavenging activity than
      EEP. However, EEP exhibited greater reducing power than WEP. A greater decrease
      of tert-butyl hydroperoxide-induced oxidative stress in RAW264.7 macrophage cells
      was also observed with EEP. Modulation of inflammatory mediators of EEP and WEP
      was evaluated on LPS plus IFN- gamma -stimulated RAW264.7 cells. EEP more
      potently suppressed LPS plus IFN- gamma -induced nitric oxide (NO) production
      than WEP. Both EEP and WEP also suppressed the expression of iNOS and COX-2
      protein levels. Collectively, these results suggest that PP possesses strong
      antioxidant and anti-inflammatory properties. 

PMID- 24744810
TI  - Memory-Enhancing Effects of the Crude Extract of Polygala tenuifolia on Aged
      Mice.
AB  - Learning and memory disorders arise from distinct age-associated processes, and
      aging animals are often used as a model of memory impairment. The root of
      Polygala tenuifolia has been commonly used in some Asian countries as memory
      enhancer and its memory improvement has been reported in various animal models.
      However, there is less research to verify its effect on memory functions in aged
      animals. Herein, the memory-enhancing effects of the crude extract of Polygala
      tenuifolia (EPT) on normal aged mice were assessed by Morris water maze (MWM) and
      step-down passive avoidance tests. In MWM tests, the impaired spatial memory of
      the aged mice was partly reversed by EPT (100 and 200 mg/kg; P < 0.05) as
      compared with the aged control mice. In step-down tests, the nonspatial memory of
      the aged mice was improved by EPT (100 and 200 mg/kg; P < 0.05). Additionally,
      EPT could increase superoxide dismutase (SOD) and catalase (CAT) activities,
      inhibit monoamine oxidase (MAO) and acetyl cholinesterase (AChE) activities, and
      decrease the levels of malondialdehyde (MDA) in the brain tissue of the aged
      mice. The results showed that EPT improved memory functions of the aged mice
      probably via its antioxidant properties and via decreasing the activities of MAO
      and AChE. 

PMID- 24744811
TI  - Effect of huanglian jiedu decoction on thoracic aorta gene expression in
      spontaneous hypertensive rats.
AB  - Objective. Hypertension is one of the most common cardiovascular disorders with
      high mortality. Here we explored the antihypertension effects of Huanglian Jiedu
      Decoction (HJD) on thoracic aorta gene expression in spontaneous hypertensive
      rats. Methods. A rat model of spontaneous hypertension was used. The gene change
      profile of thoracic aorta after JHD treatment was assessed by GeneChip(GC)
      analysis using the Agilent Whole Rat Genome Oligo Microarray. Results.
      Hypertension induced 441 genes upregulated and 417 genes downregulated compared
      with the normal control group. Treatment of HJD resulted in 76 genes
      downregulated and 20 genes upregulated. GC data analysis showed that the majority
      of change genes were involved in immune system process, developmental process,
      and cell death. Conclusion. Hypertension altered expression of many genes that
      regulate various biological functions. HJD significantly reduced hypertension and
      altered the gene expression profiles of SHR rats. These changing genes were
      involved in many cellular functions such as regulating smooth muscle contraction,
      Ca(2+) homeostasis, and NO pathway. This study provides the potential novel
      insights into hypertension and antihypertension effects of HJD. 

PMID- 24744812
TI  - Mechanisms of maggot-induced wound healing: what do we know, and where do we go
      from here?
AB  - MEDICINAL MAGGOTS ARE BELIEVED TO HAVE THREE MAJOR MECHANISMS OF ACTION ON
      WOUNDS, BROUGHT ABOUT CHEMICALLY AND THROUGH PHYSICAL CONTACT: debridement
      (cleaning of debris), disinfection, and hastened wound healing. Until recently,
      most of the evidence for these claims was anecdotal; but the past 25 years have
      seen an increase in the use and study of maggot therapy. Controlled clinical
      studies are now available, along with laboratory investigations that examine the
      interaction of maggot and host on a cellular and molecular level. This review was
      undertaken to extract the salient data, make sense, where possible, of seemingly
      conflicting evidence, and reexamine our paradigm for maggot-induced wound
      healing. Clinical and laboratory data strongly support claims of effective and
      efficient debridement. Clinical evidence for hastened wound healing is meager,
      but laboratory studies and some small, replicated clinical studies strongly
      suggest that maggots do promote tissue growth and wound healing, though it is
      likely only during and shortly after the period when they are present on the
      wound. The best way to evaluate-and indeed realize-maggot-induced wound healing
      may be to use medicinal maggots as a "maintenance debridement" modality, applying
      them beyond the point of gross debridement. 

PMID- 24744813
TI  - Hydrolysis of Glycosidic Flavonoids during the Preparation of Danggui Buxue Tang:
      An Outcome of Moderate Boiling of Chinese Herbal Mixture.
AB  - Chemical change during boiling of herbal mixture is a puzzle. By using Danggui
      Buxue Tang (DBT), a herbal decoction that contains Astragali Radix (AR) and
      Angelicae Sinensis Radix (ASR), we developed a model in analyzing the hydrolysis
      of flavonoid glycosides during the boiling of herbal mixture in water. A proper
      preparation of DBT is of great benefit to the complete extraction of bioactive
      ingredients. Boiling of DBT in water increased the solubility of AR-derived
      astragaloside IV, calycosin, formononetin, calycosin-7-O- beta -D-glucoside, and
      ononin in a time- and temperature-dependent manner: the amounts of these
      chemicals reached a peak at 2 h. The glycosidic resides of AR, calycosin-7-O-
      beta -D-glucoside, and ononin could be hydrolyzed during the moderate boiling
      process to form calycosin and formononetin, respectively. The hydrolysis
      efficiency was strongly affected by pH, temperature, and amount of herbs.
      Interestingly, the preheated herbs were not able to show this hydrolytic
      activity. The current results supported the rationality of ancient preparation of
      DBT in boiling water by moderate heat. 

PMID- 24744814
TI  - Low level laser therapy for the treatment of diabetic foot ulcers: a critical
      survey.
AB  - Diabetic foot ulcers as one of the most common complications of diabetes mellitus
      are defined as nonhealing or long-lasting chronic skin ulcers in diabetic
      patients. Multidisciplinary care for the diabetic foot is common, but treatment
      results are often unsatisfactory. Low level laser therapy (LLLT) on wound areas
      as well as on acupuncture points, as a noninvasive, pain-free method with minor
      side effects, has been considered as a possible treatment option for the diabetic
      foot syndrome. A systematic literature review identified 1764 articles on this
      topic. Finally, we adopted 22 eligible references; 8 of them were cell studies, 6
      were animal studies, and 8 were clinical trials. Cell studies and animal studies
      gave evidence of cellular migration, viability, and proliferation of fibroblast
      cells, quicker reepithelization and reformed connective tissue, enhancement of
      microcirculation, and anti-inflammatory effects by inhibition of prostaglandine,
      interleukin, and cytokine as well as direct antibacterial effects by induction of
      reactive oxygen species (ROS). The transferral of these data into clinical
      medicine is under debate. The majority of clinical studies show a potential
      benefit of LLLT in wound healing of diabetic ulcers. But there are a lot of
      aspects in these studies limiting final evidence about the actual output of this
      kind of treatment method. In summary, all studies give enough evidence to
      continue research on laser therapy for diabetic ulcers, but clinical trials using
      human models do not provide sufficient evidence to establish the usefulness of
      LLLT as an effective tool in wound care regimes at present. Further well designed
      research trials are required to determine the true value of LLLT in routine wound
      care. 

PMID- 24744815
TI  - Ethyl Acetate Extract of Artemisia anomala S. Moore Displays Potent Anti
      Inflammatory Effect.
AB  - Artemisia anomala S. Moore has been widely used in China to treat inflammatory
      diseases for hundreds of years. However, mechanisms associated with its anti
      inflammatory effect are not clear. In this study, we prepared ethyl acetate,
      petroleum ether, n-BuOH, and aqueous extracts from ethanol extract of Artemisia
      anomala S. Moore. Comparing anti-inflammatory effects of these extracts, we found
      that ethyl acetate extract of this herb (EAFA) exhibited the strongest inhibitory
      effect on nitric oxide (NO) production in LPS/IFN gamma -stimulated RAW264.7
      cells. EAFA suppressed the production of NO in a time- and dose-dependent manner
      without eliciting cytotoxicity to RAW264.7 cells. To understand the molecular
      mechanism underlying EAFA's anti-inflammatory effect, we showed that EAFA
      increased total cellular anti-oxidant capacity while reducing the amount of
      inducible nitric oxide synthase (iNOS) in stimulated RAW264.7 cells. EAFA also
      suppressed the expression of IL-1 beta and IL-6, whereas it elevates the level of
      heme oxygenase-1. These EAFA-induced events were apparently associated with NF-
      kappa B and MAPK signaling pathways because the DNA binding activity of p50/p65
      was impaired and the activities of both ERK and JNK were decreased in EFEA
      treated cells comparing to untreated cells. Our findings suggest that EAFA exerts
      its anti-inflammatory effect by inhibiting the expression of iNOS. 

PMID- 24744816
TI  - Dynamics of a new strain of the H1N1 influenza A virus incorporating the effects
      of repetitive contacts.
AB  - The respiratory disease caused by the Influenza A Virus is occurring worldwide.
      The transmission for new strain of the H1N1 Influenza A virus is studied by
      formulating a SEIQR (susceptible, exposed, infected, quarantine, and recovered)
      model to describe its spread. In the present model, we have assumed that a
      fraction of the infected population will die from the disease. This changes the
      mathematical equations governing the transmission. The effect of repetitive
      contact is also included in the model. Analysis of the model by using standard
      dynamical modeling method is given. Conditions for the stability of equilibrium
      state are given. Numerical solutions are presented for different values of
      parameters. It is found that increasing the amount of repetitive contacts leads
      to a decrease in the peak numbers of exposed and infectious humans. A stability
      analysis shows that the solutions are robust. 

PMID- 24744817
TI  - Motion-adapted catheter navigation with real-time instantiation and improved
      visualisation.
AB  - The improvements to catheter manipulation by the use of robot-assisted catheter
      navigation for endovascular procedures include increased precision, stability of
      motion and operator comfort. However, navigation through the vasculature under
      fluoroscopic guidance is still challenging, mostly due to physiological motion
      and when tortuous vessels are involved. In this paper, we propose a motion
      adaptive catheter navigation scheme based on shape modelling to compensate for
      these dynamic effects, permitting predictive and dynamic navigations. This allows
      for timed manipulations synchronised with the vascular motion. The technical
      contribution of the paper includes the following two aspects. Firstly, a dynamic
      shape modelling and real-time instantiation scheme based on sparse data obtained
      intra-operatively is proposed for improved visualisation of the 3D vasculature
      during endovascular intervention. Secondly, a reconstructed frontal view from the
      catheter tip using the derived dynamic model is used as an interventional aid to
      user guidance. To demonstrate the practical value of the proposed framework, a
      simulated aortic branch cannulation procedure is used with detailed user
      validation to demonstrate the improvement in navigation quality and efficiency. 

PMID- 24744819
TI  - Distribution of the radiation dose in multislice computer tomography of the chest
      - phantom study.
AB  - BACKGROUND: The most commonly used form of reporting doses in multislice computed
      tomography involves a CT dose index per slice and dose-length product for the
      whole series. The purpose of this study was to analyze the actual dose
      distribution in routine chest CT examination protocols using an antropomorphic
      phantom. MATERIAL/METHODS: We included in the analysis readings from a phantom
      filled with thermoluminescent detectors (Art Phantom Canberra) during routine
      chest CT examinations (64 MDCT TK LIGHT SPEED GE Medical System) performed using
      three protocols: low-dose, helical and angio-CT. RESULTS: Mean dose values (mSv)
      reported from anterior parts of the phantom sections in low-dose/helical/angio-CT
      protocols were as follows: 3.74; 16.95; 30.17; from central parts: 3.18; 14.15;
      26.71; from posterior parts: 3.01; 12.47; 24.98 respectively. Correlation
      coefficients for mean doses registered in anterior parts of the phantom between
      low-dose/helical, low-dose/angio-CT and helical/angio-CT protocols were 0.49;
      0.63; 0.36; from central parts: 0.73; 0.66; 0.83, while in posterior parts values
      were as follows: 0.06; 0.21; 0.57. CONCLUSIONS: The greatest doses were recorded
      in anterior parts of all phantom sections in all protocols in reference to
      largest doses absorbed in the anterior part of the chest during CT examination.
      The doses were decreasing from anterior to posterior parts of all sections. In
      the long axis of the phantom, in all protocols, lower doses were measured in the
      upper part of the phantom and at the very lowest part.

PMID- 24744820
TI  - Chorea, Hyperglycemia, Basal Ganglia Syndrome (C-H-BG) in an uncontrolled
      diabetic patient with normal glucose levels on presentation.
AB  - PATIENT: Female, 66 FINAL DIAGNOSIS: Chorea * hyperglycemia * Basal Ganglia
      Syndrome (C-H-BG) Symptoms: Hemibalism * hemichorea MEDICATION: - Clinical
      Procedure: - Specialty: Endocrinology and Metabolic. OBJECTIVE: Challenging
      differential diagnosis. BACKGROUND: Hemichorea-hemiballism (HCHB) is a spectrum
      of involuntary, continuous non-patterned movement involving 1 side of the body.
      Possible causes of HCHB include hemorrhagic or ischemic stroke, neoplasm,
      systemic lupus erythematosus, HHNK, Wilson's disease, and thyrotoxicosis. This
      case illustrates the need to be aware of hyperglycemia as a cause of
      hemiballism/hemichorea, which is now referred to in the medical literature as C-H
      BG (chorea, hyperglycemia, basal ganglia) syndrome. CASE REPORT: A 66-year-old
      Hispanic woman presented to our care with hemiballism/hemichorea of the right arm
      and leg of 1 week duration. She had been admitted 3 months prior with toxic
      metabolic encephalopathy secondary to hyperosmolar hyperglycemic non-ketotic
      syndrome with a blood glucose level of 984 mg/dL. Her blood glucose level was
      normal but hemoglobin A1C was 12.2%. A brain MRI revealed an asymmetric T1
      hyperintensity of the left putamen. This specific finding was compatible with
      hyperglycemia-induced hemichorea hemiballism syndrome. The hemiballism/hemichorea
      slowly improved over the course of the hospitalization with strict glycemic
      control. At the 3-month follow-up visit she had no involuntary movements of her
      extremities, and she had well controlled blood glucose levels and a hemoglobin
      A1C of 9.0. CONCLUSIONS: In a patient with normal glycemic levels but a history
      of uncontrolled diabetes, C-H-BG syndrome should be on the top of the
      differential list when the characteristic MRI findings of a hyperintensity in the
      basal ganglia are observed. This is a rare disease that deserves attention
      because it is reversible with correction of hyperglycemia. Thus, prompt
      recognition and treatment is essential to avoid adverse outcomes.

PMID- 24744818
TI  - Right ventricular dysfunction in the R6/2 transgenic mouse model of Huntington's
      disease is unmasked by dobutamine.
AB  - BACKGROUND: Increasingly, evidence from studies in both animal models and
      patients suggests that cardiovascular dysfunction is important in HD. Previous
      studies measuring function of the left ventricle (LV) in the R6/2 model have
      found a clear cardiac abnormality, albeit with preserved LV systolic function. It
      was hypothesized that an impairment of RV function might play a role in this
      condition via mechanisms of ventricular interdependence. OBJECTIVE: To
      investigate RV function in the R6/2 mouse model of Huntington's disease (HD).
      METHODS: Cardiac cine-magnetic resonance imaging (MRI) was used to determine
      functional parameters in R6/2 mice. In a first experiment, these parameters were
      derived longitudinally to determine deterioration of cardiac function with
      disease progression. A second experiment compared the response to a stress test
      (using dobutamine) of wildtype and early-symptomatic R6/2 mice. RESULTS: There
      was progressive deterioration of RV systolic function with age in R6/2 mice.
      Furthermore, beta-adrenergic stimulation with dobutamine revealed RV dysfunction
      in R6/2 mice before any overt symptoms of the disease were apparent. CONCLUSIONS:
      This work adds to accumulating evidence of cardiovascular dysfunction in R6/2
      mice, describing for the first time the involvement of the right ventricle.
      Cardiovascular dysfunction should be considered, both when treatment strategies
      are being designed, and when searching for biomarkers for HD.

PMID- 24744821
TI  - EDITORIAL: TECHNOLOGY, INNOVATION, AND HEALTH.

PMID- 24744822
TI  - UNDERSTANDING THE HIGH COST OF SUCCESS IN UNIVERSITY RESEARCH.
AB  - In light of new transparency in budgeting and expenditures expected of central
      research administration and reductions in the amount of indirect cost revenues
      distributed to colleges, departments, and faculty, universities must present a
      more accurate perspective on the "real costs" of research, costs that extend well
      beyond support for the central research office. The purpose of this article is to
      illuminate the significant gap between the real costs of research within
      universities and the funding that is available to support them.

PMID- 24744825
TI  - Economic burden of colorectal cancer in Korea.
AB  - OBJECTIVES: The incidence and survival rate of colorectal cancer in Korea are
      increasing because of improved screening, treatment technologies, and lifestyle
      changes. In this aging population, increases in economic cost result. This study
      was conducted to estimate the economic burden of colorectal cancer utilizing
      claims data from the Health Insurance Review and Assessment Service. METHODS:
      Economic burdens of colorectal cancer were estimated using prevalence data and
      patients were defined as those who received ambulatory treatment from medical
      institutions or who had been hospitalized due to colorectal cancer under the
      International Classification of Disease 10th revision codes from C18-C21. The
      economic burdens of colorectal cancer were calculated as direct costs and
      indirect costs. RESULTS: The prevalence rate (per 100 000 people) of those who
      were treated for colorectal cancer during 2010 was 165.48. The economic burdens
      of colorectal cancer in 2010 were 3 trillion and 100 billion Korean won (KRW),
      respectively. Direct costs included 1 trillion and 960 billion KRW (62.85%),
      respectively and indirect costs were 1 trillion and 160 billion (37.15%),
      respectively. CONCLUSIONS: Colorectal cancer has a large economic burden. Efforts
      should be made to reduce the economic burden of the disease through primary and
      secondary prevention.

PMID- 24744824
TI  - Environmental mercury and its toxic effects.
AB  - Mercury exists naturally and as a man-made contaminant. The release of processed
      mercury can lead to a progressive increase in the amount of atmospheric mercury,
      which enters the atmospheric-soil-water distribution cycles where it can remain
      in circulation for years. Mercury poisoning is the result of exposure to mercury
      or mercury compounds resulting in various toxic effects depend on its chemical
      form and route of exposure. The major route of human exposure to methylmercury
      (MeHg) is largely through eating contaminated fish, seafood, and wildlife which
      have been exposed to mercury through ingestion of contaminated lower organisms.
      MeHg toxicity is associated with nervous system damage in adults and impaired
      neurological development in infants and children. Ingested mercury may undergo
      bioaccumulation leading to progressive increases in body burdens. This review
      addresses the systemic pathophysiology of individual organ systems associated
      with mercury poisoning. Mercury has profound cellular, cardiovascular,
      hematological, pulmonary, renal, immunological, neurological, endocrine,
      reproductive, and embryonic toxicological effects. 

PMID- 24744826
TI  - Association between socioeconomic status and obesity in adults: evidence from the
      2001 to 2009 Korea national health and nutrition examination survey.
AB  - OBJECTIVES: The present study examined relationships between socioeconomic status
      (SES) and obesity and body mass index (BMI) as well as the effects of health
      related behavioral and psychological factors on the relationships. METHODS: A
      cross-sectional population-based study was conducted on Korean adults aged 20 to
      79 years using data from the 2001, 2005, and 2007 to 2009 Korea National Health
      and Nutrition Examination Survey. Multivariate logistic and linear regression
      models were used to estimate odds ratios of obesity and mean differences in BMI,
      respectively, across SES levels after controlling for health-related behavioral
      and psychological factors. RESULTS: We observed significant gender-specific
      relationships of SES with obesity and BMI after adjusting for all covariates. In
      men, income, but not education, showed a slightly positive association with BMI
      (p<0.05 in 2001 and 2005). In women, education, but not income, was inversely
      associated with both obesity and BMI (p<0.0001 in all datasets). These
      relationships were attenuated with adjusting for health-related behavioral
      factors, not for psychological factors. CONCLUSIONS: Results confirmed gender
      specific disparities in the associations of SES with obesity and BMI among adult
      Korean population. Focusing on intervention for health-related behaviors may be
      effective to reduce social inequalities in obesity.

PMID- 24744827
TI  - The incidence of stroke by socioeconomic status, age, sex, and stroke subtype: a
      nationwide study in Korea.
AB  - OBJECTIVES: To date, studies have not comprehensively demonstrated the
      relationship between stroke incidence and socioeconomic status. This study
      investigated stroke incidence by household income level in conjunction with age,
      sex, and stroke subtype in Korea. METHODS: Contributions by the head of household
      were used as the basis for income levels. Household income levels for 21 766 036
      people were classified into 6 groups. The stroke incidences were calculated by
      household income level, both overall within income categories and further by age
      group, sex, and stroke subtype. To present the inequalities among the six ranked
      groups in a single value, the slope index of inequality and relative index of
      inequality were calculated. RESULTS: In 2005, 57 690 people were first-time
      stroke patients. The incidences of total stroke for males and females increased
      as the income level decreased. The incidences of stroke increased as the income
      level decreased in those 74 years old and under, whereas there was no difference
      by income levels in those 75 and over. Intracerebral hemorrhage for the males
      represented the highest inequality among stroke subtypes. Incidences of
      subarachnoid hemorrhage did not differ by income levels. CONCLUSIONS: The
      incidence of stroke increases as the income level decreases, but it differs
      according to sex, age, and stroke subtype. The difference in the relative
      incidence is large for male intracerebral hemorrhage, whereas the difference in
      the absolute incidence is large for male ischemic stroke.

PMID- 24744829
TI  - Outdoor (1->3)-beta-D-glucan levels and related climatic factors.
AB  - OBJECTIVES: To evaluate the monthly variation in the airborne (1->3)-beta-D
      glucan level throughout one year and its relationship with climatic factors
      (temperature, relative humidity, wind speed, hours of daylight, cloud cover, and
      pollen counts). METHODS: A total of 106 samples were collected using a two-stage
      cyclone sampler at five outdoor sampling locations (on top of 5 university
      buildings). The kinetic limulus amebocyte lysate assay was used to obtain (1->3)
      beta-D-glucan levels. RESULTS: Airborne (1->3)-beta-D-glucan levels were
      significantly higher in the spring, particularly in April, and temperature was
      significantly related to (1->3)-beta-D-glucan levels (r =0.339, p<0.05).
      CONCLUSIONS: (1->3)-beta-D-glucan levels may be highest in the spring, and
      outdoor temperature may influence (1->3)-beta-D-glucan levels.

PMID- 24744828
TI  - Associations between socio-demographic characteristics and healthy lifestyles in
      Korean Adults: the result of the 2010 Community Health Survey.
AB  - OBJECTIVES: Several previous studies have found that healthy behaviors
      substantially reduce non-communicable disease incidence and mortality. The
      present study was performed to estimate the prevalence of four modifiable healthy
      behaviors and a healthy lifestyle among Korean adults according to socio
      demographic and regional factors. METHODS: We analyzed data from 199 400 Korean
      adults aged 19 years and older who participated in the 2010 Korean Community
      Health Survey. We defined a healthy lifestyle as a combination of four modifiable
      healthy behaviors: non-smoking, moderate alcohol consumption, regular walking,
      and a healthy weight. We calculated the prevalence rates and odds ratios of each
      healthy behavior and healthy lifestyle according to socio-demographic and
      regional characteristics. RESULTS: The prevalence rates were as follows: non
      smoking, 75.0% (53.7% in men, 96.6% in women); moderate alcohol consumption,
      88.2% (79.7% in men, 96.9% in women); regular walking, 45.0% (46.2% in men, 43.8%
      in women); healthy weight, 77.4% (71.3% in men, 73.6% in women); and a healthy
      lifestyle, 25.5% (16.4% in men, 34.6% in women). The characteristics associated
      with a low prevalence of healthy lifestyle were male gender, younger age (19 to
      44 years of age), low educational attainment, married, living in a rural area,
      living in the Chungcheong, Youngnam, or Gwangwon-Jeju region, and poorer self
      rated health. CONCLUSIONS: Further research should be implemented to explore the
      explainable factors of disparities for socio-demographic and regional
      characteristics to engage in the healthy lifestyle among adults.

PMID- 24744830
TI  - Chromatin diminution in Copepoda (Crustacea): pattern, biological role and
      evolutionary aspects.
AB  - This article provides an overview of research on chromatin diminution (CD) in
      copepods. The phenomenology, mechanisms and biological role of CD are discussed.
      A model of CD as an alternative means of regulating cell differentiation is
      presented. While the vast majority of eukaryotes inactivate genes that are no
      longer needed in development by heterochromatinization, copepods probably use CD
      for the same purpose. It is assumed that the copepods have exploited CD as a tool
      for adaptation to changing environmental conditions and as a mechanism for
      regulating the rate of evolutionary processes. 

PMID- 24744831
TI  - New karyologycal data and cytotaxonomic considerations on small mammals from
      Santa Virginia (Parque Estadual da Serra do Mar, Atlantic Forest, Brazil).
AB  - Atlantic Forest, in the eastern coast of Brazil, is a hotspot of biodiversity of
      mammals, and Parque Estadual da Serra do Mar (PESM) is the largest continuous
      area of this biome. Here, we characterized the karyotype composition of the small
      mammals from Santa Virginia, a region in the northern part of PESM. Specimens
      were collected from July 2008 to September 2009. We identified 17 species (13
      rodents and 4 marsupials) from which 7 exhibited species-specific karyotypes,
      illustrating the importance of karyotype information in cytotaxonomy. We report
      for first time the karyotype of Monodelphis scalops (Thomas, 1888) and two new
      records for PESM: Akodon montensis Thomas, 1913 and Brucepattersonius soricinus
      Hershkovitz, 1998. Cytogenetic polymorphisms were detected for some species
      trapped in the area. Our results show the importance of Santa Virginia / PESM in
      addressing studies for the conservation of small mammal wildlife in the Atlantic
      Forest. 

PMID- 24744832
TI  - Karyotypes of parasitic wasps of the family Eulophidae (Hymenoptera) attacking
      leaf-mining Lepidoptera (Gracillariidae, Gelechiidae).
AB  - Karyotypes of eleven parasitoid species of the family Eulophidae were examined,
      namely, Chrysocharis laomedon (Walker, 1839) (2n = 10), Chrysocharis sp. aff.
      laomedon (n = 5, 2n = 10), Chrysocharis sp. aff. albipes (Ashmead, 1904) (2n =
      12), Mischotetrastichus petiolatus (Erdos, 1961) (n = 6, 2n = 12),
      Minotetrastichus frontalis (Nees, 1834) (n = 5, 2n = 10), Cirrospilus pictus
      (Nees, 1834) (2n = 12), Hyssopus geniculatus (Hartig, 1838) (2n = 16), Sympiesis
      gordius (Walker, 1839) (2n = 12), S. sericeicornis (Nees, 1834) (2n = 12),
      Pnigalio agraules (Walker, 1839) (2n = 12 + 0-2B) and Pnigalio gyamiensis
      Myartseva & Kurashev, 1990 (2n = 12 + 0-6B) reared from Phyllonorycter
      acerifoliella (Zeller, 1839), Ph. apparella (Herrich-Schaffer, 1855), Ph. issikii
      (Kumata, 1963) (Gracillariidae) and Chrysoesthia sexguttella (Thunberg, 1794)
      (Gelechiidae). Chromosome sets of all species except P. agraules and P.
      gyamiensis were studied for the first time. B chromosomes were detected in the
      two latter species; in P. gyamiensis, the maximum number of B chromosomes
      represents the highest value known for parasitic wasps to date. 

PMID- 24744833
TI  - Multiple sex chromosome systems in howler monkeys (Platyrrhini, Alouatta).
AB  - In light of the multiple sex chromosome systems observed in howler monkeys
      (Alouatta Lacepede, 1799) a combined cladistic analysis using chromosomal and
      molecular characters was applied to discuss the possible origin of these systems.
      Mesoamerican and South American howlers were karyologically compared. FISH
      analysis using the chromosome painting probes for the #3 and #15 human
      chromosomes was applied to corroborate the homeology of the sexual systems. We
      found that the HSA3/15 syntenic association, present in the sex chromosome
      systems of South American Howlers, is not present in those of Mesoamerican ones.
      The autosomes involved in the translocation that formed the sexual systems in the
      Mesoamerican and South American species are different, thus suggesting an
      independent origin. Parsimony analysis resolved the phylogenetic relationships
      among howler species, demonstrating utility of the combined approach. A
      hypothesis for the origin of the multiple sex chromosome systems for the genus is
      proposed. 

PMID- 24744834
TI  - Karyomorphometry on three polyploid species of Arum L. (Araceae, Aroideae).
AB  - In this study three polyploid Arum Linnaeus, 1753 species from Southern Italy
      were chromosomally investigated. Arum italicum Miller, 1768 was found to have 2n
      = 84 chromosomes and a karyotype composed of numerous asymmetric chromosomes.
      Arum maculatum Linnaeus, 1753 and Arum apulum (Carano) P. C. Boyce, 1993 were
      found to have 2n = 56 chromosomes. In the examined taxa some chromosome pairs
      were characterized by the presence of weakly coloured Feulgen-stained segments.
      The karyotype morphology of Arum italicum was found to be similar to that of Arum
      maculatum, but the more asymmetrical karyotype and numerous weakly coloured
      Feulgen-stained segments observed in the former suggest the existence of more
      extensive rearrangements. In contrast, Arum apulum was observed to have a
      symmetrical karyotype. The A1, A2 and SYi karyotype asymmetry indices are
      presented. The relationships between these taxa in terms of karyotype morphology
      and evolution are discussed. 

PMID- 24744835
TI  - Traumatic Infra-renal Aortic Dissection After a High-energy Trauma: A Case Report
      of a Primary Missed Diagnosis.
AB  - A traumatic infra-renal aortic dissection is a rare but life-threatening injury
      that follows deceleration injuries. The mechanism of blunt abdominal aortic
      injury involves both direct and indirect forces. The successful management of
      patients with traumatic injuries depends on a prompt suspicion of the injury and
      early diagnosis and therapy. Missed injuries in trauma patients are well
      described phenomena and implementation of the ATLS(r) trauma schedule led to a
      decrease in the number of missed injuries, but trauma computed tomography (CT)
      scans in injured patients are still not standard. We report on a 54-year old
      Caucasian female patient who was involved in a car accident. The fellow passenger
      of the car was seriously injured. The patient had been previously treated at two
      different hospitals, and a dislocated acetabular fracture had been diagnosed.
      Because of this injury, the patient was transferred to our institution, a level 1
      trauma-center where, according to the nature of the accident as a high-energy
      trauma, a complete polytrauma management was performed at the time of admission.
      During the body check, a moderate tension of the lower parts of the abdomen was
      detected. During the CT scan, an aneurysm of the infra-renal aorta with a
      dissection from the height of the second lumbar vertebral body to the iliac
      artery was observed. The patient required an operation on the day of admission.
      After 19 days post-trauma care the patient was able to leave our hospital in good
      general condition. Therefore, missed injuries in multiple injury patients could
      be fatal, and it is essential that the orthopedic surgeon leaves room for
      suspicion of injuries based on the nature of the trauma. Traumatic injuries of
      the abdominal aorta are rare. According to the ATLS(r) trauma schedule, all of
      the patients who have experienced high-energy trauma and associated fractures
      should undergo routine screening using a trauma CT scan with contrast agents to
      detect potential life-threatening injuries. In case of abdominal trauma, an
      aortic dissection, which can easily be overlooked, has to be considered. 

PMID- 24744836
TI  - Do Bisphosphonate-related Atypical Femoral Fractures and Osteonecrosis of the Jaw
      Affect the Same Group of Patients? A Pilot Study.
AB  - Bisphosphonates (BPs) are commonly used drugs in clinical practice. In this pilot
      study, we investigated whether bisphosphonate-related atypical femoral fractures
      (AFF) and osteonecrosis of the jaw (ONJ) occurred simultaneously in the same
      group of patients. Six ONJ patients were examined by an orthopedic surgeon and 5
      AFF patients were examined by a dentist to look for manifestations of
      simultaneous occurrence of AFF in ONJ patients and vice versa. The required
      radiological investigations and previous medical and dental records were
      available. No simultaneous occurrence of AFF and ONJ was found in the examined
      patients. In this pilot study with limited sample size, no manifestations of
      simultaneous occurrence of AFF and ONJ were found. This could be an indication
      that these complications have different pathophysiologies and affect different
      subgroups of patients on long-term BP treatment. 

PMID- 24744837
TI  - Comparison of Continuous Femoral Nerve Block, Caudal Epidural Block, and
      Intravenous Patient-controlled Analgesia in Pain Control After Total Hip
      Arthroplasty: A Prospective Randomized Study.
AB  - Thirty-six patients who underwent primary unilateral total hip arthroplasty (THA)
      were randomly allocated to 4 groups with different pain control protocols;
      continuous femoral nerve block (FNB group), single-shot caudal epidural block
      with morphine (EB group), intravenous patient-controlled analgesia with fentanyl
      (IV-PCA group), and systemic administration of nonsteroidal anti-inflammatory
      drugs (NSAIDs group). Postoperative pain was assessed using the numerical rating
      scale (NRS) scores and the analgesic effect was compared among the groups. The
      NRS upon arrival at the recovery room and 6 hours after surgery in the FNB, EB,
      and IV-PCA groups were significantly lower than that in the NSAIDs group. The
      amount of additional analgesics requested by the patient was smaller in the FNB,
      EB, and IV-PCA groups as compared to the NSAIDs group. Regarding the
      complications related to the analgesia, 5 of the 9 patients in the IV-PCA group
      complained nausea and vomiting and received antiemetic drugs. Delay in the
      rehabilitation process due to drowsiness was encountered in 3 patients in this
      group, while no patient in the FNB and EB groups suffered from delayed
      rehabilitation. Considering both the analgesic effect and the potential risk of
      complications, continuous femoral nerve blocks and caudal epidural blocks for are
      recommended for postoperative pain control after THA procedure. 

PMID- 24744838
TI  - Surgery for wrist Ganglia: one-hundred and twenty-two patients reviewed 8 years
      after operation.
AB  - Wrist ganglia give few symptoms, but are a common reason for referral to a hand
      surgeon. We studied patient long-term satisfaction after operation. We reviewed
      122 patients, who were operated for dorsal (n=82) and volar (n=40) wrist ganglia
      8 years before (range 3-11). Three radial arteries were injured during surgery
      for volar a ganglion. By the time of review 33 patients (27%) had a recurrence or
      had been re-operated. Radical surgery did not reduce the recurrence rate
      significantly. Reported general complaints from the wrist improved from a mean
      visual analogue scores (VAS, 0=best; 100= worst) of 56 before surgery to VAS 14
      at review and unsightliness from VAS 50 to VAS 14. Patients were equally happy
      with transverse and longitudinal scars. Ten patients (8%) stated that they would
      not have consented to surgery if they had known the outcome in advance. We
      conclude that, in spite of a high recurrence rate, most patients are happy with
      the results of surgery. 

PMID- 24744839
TI  - Early knee osteoarthritis management should first address mechanical joint
      overload.
AB  - Early knee osteoarthritis poses a therapeutic dilemma to the musculoskeletal
      clinician. Despite the recent interest in arthroscopic and injectable
      regenerative therapies intended to repair or restore a focal target such as
      cartilage, meniscus, or subchondral bone, none have been shown to slow disease
      progression. A likely cause of these disappointing treatment outcomes is the
      failure to address chronic and excessive loading of the knee joint. A growing
      body of evidence suggests that first-line therapies for early knee osteoarthritis
      should emphasize unloading the knee joint since any potential therapeutic benefit
      of regenerative therapies will likely be attenuated by excessive mechanical
      demand at the knee joint. Minimally invasive medical devices such as patient
      specific interpositional implants and extracapsular joint unloading implants are
      currently in development to address this clinical need. 

PMID- 24744840
TI  - Changes in strain patterns after implantation of a short stem with metaphyseal
      anchorage compared to a standard stem: an experimental study in synthetic bone.
AB  - Short stem hip arthroplasties with predominantly metaphyseal fixation, such as
      the METHA(r) stem (Aesculap, Tuttlingen, Germany), are recommended because they
      are presumed to allow a more physiologic load transfer and thus a reduction of
      stress-shielding. However, the hypothesized metaphyseal anchorage associated with
      the aforementioned benefits still needs to be verified. Therefore, the METHA
      short stem and the Bicontact(r) standard stem (Aesculap, Tuttlingen, Germany)
      were tested biomechanically in synthetic femora while strain gauges monitored
      their corresponding strain patterns. For the METHA stem, the strains in all
      tested locations including the region of the calcar (87% of the non-implanted
      femur) were similar to conditions of synthetic bone without implanted stem. The
      Bicontact stem showed approximately the level of strain of the non-implanted
      femur on the lateral and medial aspect in the proximal diaphysis of the femur. On
      the anterior and posterior aspect of the proximal metaphysis the strains reached
      averages of 78% and 87% of the non-implanted femur, respectively. This study
      revealed primary metaphyseal anchorage of the METHA short stem, as opposed to a
      metaphyseal-diaphyseal anchorage of the Bicontact stem. 

PMID- 24744841
TI  - Confronting hip resurfacing and big femoral head replacement gait analysis.
AB  - Improved hip kinematics and bone preservation have been reported after
      resurfacing total hip replacement (THRS). On the other hand, hip kinematics with
      standard total hip replacement (THR) is optimized with large diameter femoral
      heads (BFH-THR). The purpose of this study is to evaluate the functional outcomes
      of THRS and BFH-THR and correlate these results to bone preservation or the large
      femoral heads. Thirty-one patients were included in the study. Gait speed,
      postural balance, proprioception and overall performance. Our results
      demonstrated a non-statistically significant improvement in gait, postural
      balance and proprioception in the THRS confronting to BFH-THR group. THRS provide
      identical outcomes to traditional BFH-THR. The THRS choice as bone preserving
      procedure in younger patients is still to be evaluated. 

PMID- 24744842
TI  - Posterior sternoclavicular dislocations: a brief review and technique for closed
      management of a rare but serious injury.
AB  - Posterior sternoclavicular dislocations are rare but serious injuries. The
      proximity of the medial clavicle to the vital structures of the mediastinum
      warrants caution with management of the injury. Radiographs are the initial
      imaging test, though computed tomography and magnetic resonance imaging are
      essential for diagnosis and preoperative planning. This paper presents an
      efficient diagnostic approach and effective technique of closed reduction of
      posterior sternoclavicular dislocations with a brief review of open and closed
      reduction procedures. 

PMID- 24744843
TI  - Correctly identify practitioners and put adverse events of spinal manipulation
      into perspective.

PMID- 24744844
TI  - Response letter concerning: correctly identify practitioners and put adverse
      events of spinal manipulation into perspective.

PMID- 24744845
TI  - Effects of using the nintendo wii fit plus platform in the sensorimotor training
      of gait disorders in Parkinson's disease.
AB  - The use of the Nintendo Wii has been considered a good alternative in the motor
      rehabilitation of individuals with Parkinson's disease (PD), requiring
      simultaneous interaction to develop strategies for physical, visual, auditory,
      cognitive, psychological and social activities in the performing of virtual
      activities, resulting in improvement in functional performance and gait. The aim
      of this study was to analyze the effect of virtual sensorimotor activity on gait
      disorders in people with PD. Fifteen subjects with a clinical diagnosis of PD
      were submitted to the Unified Parkinson's Disease Rating Scale (UPDRS III),
      Schwab and England Activities of Daily Living Scale (SE), Functional Independence
      Measure (FIM), and biomechanical gait analysis using digital images taken with a
      video camera before and after the treatment program. The activities with the
      Nintendo Wii virtual platform were standardized into three categories: aerobics,
      balance and Wii plus exercises. Participants carried out separate virtual
      exercises for 40 min, twice a week, for a total of 14 sessions. The program
      improved sensorimotor performance in PD gait, with an increase in stride length
      and gait speed, in addition to a reduction in motor impairment, especially in
      items of rigidity and flexibility of the lower limbs evaluated by UPDRS III, and
      greater functional independence, as evidenced in the SE and FIM scales.
      Improvements in items related to locomotion and stair climbing were also
      observed. The training was effective in motor recovery in chronic
      neurodegenerative diseases, showing improvement in motor performance and
      functional independence in individuals with PD. 

PMID- 24744846
TI  - Diastolic Function in Steinert's Disease.
AB  - Myotonic dystrophy type 1 (MD) is the most common autosomal dominant muscular
      dystrophy in adults. Cardiac involvement is mainly characterized by conduction
      abnormalities and arrhythmias. We sought to assess diastolic function in MD
      patients. Echocardiography-Doppler was performed in Steinert's patients and in a
      control group completed by tissue Doppler imaging (TDI). Twenty-six patients with
      Steinert's disease were included in the study and were compared to a control
      group. Mean age was similar in the 2 groups (45.1 years +/-10.9 in Steinert's
      patients vs 42.1 years +/-11 in control group p 0.4). 6 /26 patients with
      Steinert's disease disclosed a left ventricular (LV) ejection fraction <50%. Mean
      left atrial (LA) diameter was statistically different between Steinert's patients
      and patients in group control (27.8 mm +/-8.5 vs 19.7 mm +/-4; P=0.0018). Mean
      peak E/A mitral ratio was 1.29+/-0.45 in Steinert's patients vs 1.36+/-0.4 in
      control group (P=0.6). We found an increase of the mitral E deceleration time in
      Steinert's patients in comparison with patients in control group (219 ms +/-53 vs
      176 ms +/-29; P=0.013). Mean peak lateral early diastolic velocity Ea was similar
      in the 2 groups (12.3 cm/s +/-3 vs 13.1 cm/s +/-3.8; P=0.50). Mean peak septal
      early diastolic velocity was similar in the 2 groups (11.2 cm/s +/-2 vs 10.4+/-2;
      P=0.51). We found an increase of the LA diameter and an increase of the mitral
      deceleration time in Steinert's patients that suggest diastolic abnormalities. 

PMID- 24744847
TI  - Methomyl poisoning presenting with decorticate posture and cortical blindness.
AB  - Methomyl is a potent pesticide that is widely used in the field of agriculture.
      The systemic toxic effects of methomyl have been well described. However, the
      neurological effects of methomyl intoxication are not well understood. In this
      study, we report a 61-year-old Taiwanese man sent to our emergency department
      because of altered mental status. His family stated that he had consumed liquid
      methomyl in a suicide attempt. He was provided cardiopulmonary resuscitation
      because of unstable vital signs. He was then sent to an intensive care unit for
      close observation. On the second day of admission, he regained consciousness but
      exhibited irregular limb and torso posture. On the sixth day, he started to
      complain of blurred vision. An ophthalmologist was consulted but no obvious
      abnormalities could be identified. On suspicion of cerebral disease, a
      neurologist was consulted. Further examination revealed cortical blindness and
      decorticate posture. Cerebral magnetic resonance imaging (MRI) was arranged,
      which identified bilateral occipital regions lesions. The patient was
      administered normal saline and treated with aspirin and piracetam for 3 weeks in
      hospital. During the treatment period, his symptom of cortical blindness
      resolved, whereas his decorticate posture was refractory. Follow-up brain MRI
      results supported our clinical observations by indicating the disappearance of
      the bilateral occipital lesions and symmetrical putaminal high signal
      abnormalities. In this article, we briefly discuss the possible mechanisms
      underlying the cerebral effects of methomyl poisoning. Our study can provide
      clinicians with information on the manifestations of methomyl intoxication and an
      appropriate treatment direction. 

PMID- 24744848
TI  - Posterior reversible encephalopathy syndrome: differences between pregnant and
      non-pregnant patients.
AB  - Posterior reversible encephalopathy syndrome (PRES) is a clinical-radiologic
      entity not yet understood, that presents with transient neurologic symptoms and
      particular radiological findings. Few papers show the differences between
      pregnant and non-pregnant patients. We review the cases of 38 women diagnosed
      with PRES, in order to find significant differences between pregnant (18) and non
      pregnant (20) patients. We found differences among the age of patients (25.83
      years old in pregnant and 29.31 years old in non pregnant; P=0.001); in the mean
      of highest systolic blood pressure, that was higher in non-pregnant group
      (185:162 mmHg; P=0.121); and in creatinine levels that was higher in non-pregnant
      group (3.47:1.04 mg/dL; P=0.001). To our knowledge, just a few papers analyzed
      whether PRES syndrome presented in the same way in pregnant and non-pregnant
      patients. The differences and the possible pathophisiology of this syndrome still
      remain enigmatic. 

PMID- 24744849
TI  - Lower total and percent of high-molecular-weight adiponectin concentration in
      South Asian kidney transplant recipients.
AB  - BACKGROUND: Ethnicity is an important determinant of post-renal transplant
      outcomes. Limited data are available on cardiovascular risk differences in kidney
      transplant recipients (KTR) based on ethnicity. METHODS: A group of 129
      clinically stable age-matched KTR [43 South Asian (SA), 86 Caucasian]) were
      assessed for plasma total and high-molecular-weight (HMW) adiponectin, cystatin
      C, apolipoproteins A1 and B, C-reactive protein, uric acid, urine albumin-to
      creatinine ratio, estimated glomerular filtration rate (eGFR) and transplant
      specific plus traditional Framingham risk factors. SA and Caucasians were
      compared by t-tests, Wilcoxon rank-sum or chi-square testing. Accounting for the
      matched design, multivariable linear regression was performed to determine
      predictors of adiponectin concentrations. RESULTS: SA did not differ from
      Caucasians in background cardiac disease or cardioprotective medication use or
      risk factors other than smoking (26 versus 56%, P = 0.001). Total adiponectin
      (9.5 +/- 3.5 versus 12.9 +/- 6.7 MUmg/mL, P < 0.001) and HMW adiponectin (22 +/-
      9 versus 29 +/- 11%, P < 0.001) were significantly lower in SA. Determinants of
      total adiponectin included SA ethnicity (P = 0.02), cystatin C-eGFR (P < 0.001),
      high-density lipoprotein (HDL) cholesterol (P < 0.0001) and waist-to-hip ratio (P
      < 0.001), while those of HMW adiponectin included SA ethnicity (P < 0.001),
      cystatin C-eGFR (P = 0.03) and HDL cholesterol (P = 0.001). There were no
      important differences in the other measured biomarkers. CONCLUSION: Total and HMW
      adiponectin concentrations are lower in SA KTR and may be promising exploratory
      biomarkers of post-transplant cardiovascular risk.

PMID- 24744851
TI  - Increased microvascular flow and foot sensation with mild continuous external
      compression.
AB  - Intermittent pneumatic compression of the calf and foot increases inflow to the
      popliteal artery and skin. We hypothesize that mild, continuous pneumatic
      compression of the lower extremities of type 2 diabetic patients increases
      microvascular blood flow to skin (SBF) and muscle (MBF) and improves sensation in
      feet. Data were collected on 19 healthy volunteers and 16 type 2 diabetic
      patients. Baseline values of SBF, MBF, and foot sensation were recorded in one
      leg. The lower extremity was then subjected to 30 mmHg of continuous external air
      pressure for 30 min, whereas SBF and MBF were continuously monitored. Sensation
      was reassessed after pressure was released. During 30 mmHg continuous external
      compression, the healthy control group significantly increased MBF by 39.8% (P <
      0.01). Sensation of the foot in this group improved significantly by 49.8% (P <
      0.01). In the diabetic group, there was a significant increase in MBF of 17.7% (P
      = 0.03). Also sensation improved statistically by 40.2% (P = 0.03). Importantly
      and counterintuitively, MBF and foot sensation both increase after 30 min of leg
      compression at 30 mmHg. Therefore, mild, continuous pneumatic compression may be
      a new approach for treating diabetic patients with compromised leg perfusion and
      sensation. 

PMID- 24744852
TI  - Peptide transporter isoforms are discriminated by the fluorophore-conjugated
      dipeptides beta-Ala- and d-Ala-Lys-N-7-amino-4-methylcoumarin-3-acetic acid.
AB  - Peptide transporters of the SLC15 family are classified by structure and function
      into PEPT1 (low-affinity/high-capacity) and PEPT2 (high-affinity/low-capacity)
      isoforms. Despite the differences in kinetics, both transporter isoforms are
      reckoned to transport essentially all possible di- and tripeptides. We here
      report that the fluorophore-conjugated dipeptide derivatives beta-Ala-Lys-N-7
      amino-4-methylcoumarin-3-acetic acid (beta-AK-AMCA) and d-Ala-Lys-N-7-amino-4
      methylcoumarin-3-acetic acid (d-AK-AMCA) are transported by distinct PEPT
      isoforms in a species-specific manner. Transport of the fluorophore peptides was
      studied (1) in vitro after heterologous expression in Xenopus oocytes of PEPT1
      and PEPT2 isoforms from different vertebrate species and of PEPT1 and PEPT2
      transporters from Caenorhabditis elegans by using electrophysiological and
      fluorescence methods and (2) in vivo in C. elegans by using fluorescence methods.
      Our results indicate that both substrates are transported by the vertebrate
      "renal-type" and the C. elegans "intestinal-type" peptide transporter only. A
      systematic analysis among species finds four predicted amino acid residues along
      the sequence that may account for the substrate uptake differences observed
      between the vertebrate PEPT1/nematode PEPT2 and the vertebrate PEPT2/nematode
      PEPT1 subtype. This selectivity on basis of isoforms and species may be helpful
      in better defining the structure-function determinants of the proteins of the
      SLC15 family. 

PMID- 24744853
TI  - Mechanical correlates of dyspnea in bronchial asthma.
AB  - We hypothesized that dyspnea and its descriptors, that is, chest tightness,
      inspiratory effort, unrewarded inspiration, and expiratory difficulty in asthma
      reflect different mechanisms of airflow obstruction and their perception varies
      with the severity of bronchoconstriction. Eighty-three asthmatics were studied
      before and after inhalation of methacholine doses decreasing the 1-sec forced
      expiratory volume by ~15% (mild bronchoconstriction) and ~25% (moderate
      bronchoconstriction). Symptoms were examined as a function of changes in lung
      mechanics. Dyspnea increased with the severity of obstruction, mostly because of
      inspiratory effort and chest tightness. At mild bronchoconstriction, multivariate
      analysis showed that dyspnea was related to the increase in inspiratory
      resistance at 5 Hz (R 5) (r (2) = 0.10, P = 0.004), chest tightness to the
      decrease in maximal flow at 40% of control forced vital capacity, and the
      increase in R 5 at full lung inflation (r (2) = 0.15, P = 0.006), inspiratory
      effort to the temporal variability in R 5-19 (r (2) = 0.13, P = 0.003), and
      unrewarded inspiration to the recovery of R 5 after deep breath (r (2) = 0.07, P
      = 0.01). At moderate bronchoconstriction, multivariate analysis showed that
      dyspnea and inspiratory effort were related to the increase in temporal
      variability in inspiratory reactance at 5 Hz (X 5) (r (2) = 0.12, P = 0.04 and r
      (2) = 0.18, P < 0.001, respectively), and unrewarded inspiration to the decrease
      in X 5 at maximum lung inflation (r (2) = 0.07, P = 0.04). We conclude that
      symptom perception is partly explained by indexes of airway narrowing and loss of
      bronchodilatation with deep breath at low levels of bronchoconstriction, but by
      markers of ventilation heterogeneity and lung volume recruitment when
      bronchoconstriction becomes more severe. 

PMID- 24744854
TI  - Sphingosine-1-phosphate acts as a key molecule in the direct mediation of renal
      fibrosis.
AB  - The major sphingolipid metabolite, sphingosine-1-phosphate (S1P), has important
      biological functions. S1P serves as a ligand for a family of five G-protein
      coupled receptors with distinct signaling pathways regulating important
      biological pathways. S1P induces renal fibrosis through an inflammatory pathway.
      However, its direct fibrosis-inducing effect on the kidney has not been shown.
      The role of S1P as a direct mediator of renal fibrosis was investigated in normal
      rat kidney interstitial fibroblast (NRK-49F) cells (in vitro) and kidneys of a
      unilateral ureteral obstruction (UUO) mouse model (in vivo). To clarify the role
      of S1P in renal fibrosis, we adopted nude UUO mice with immune response deficits.
      NRK-49F cells were stimulated with various concentrations of exogenous S1P and
      FTY720 (a S1P receptor agonist) or N,N-dimethylsphingosine (DMS; a sphingosine
      kinase inhibitor). C57BL6 and nude UUO mice were pretreated with FTY720, DMS, or
      saline. Expression levels of alpha-smooth muscle actin (a-SMA), E-cadherin,
      collagen type 1 (COL1), collagen type 4 (COL4), tissue inhibitor of matrix
      metalloproteinase-1 (TIMP1), and plasminogen activator inhibitor-1 (PAI1) were
      examined. S1P stimulated fibrosis in NRK-49F cells and UUO mice. Increased a-SMA,
      COL1, COL4, TIMP1, and PAI1 and decreased E-cadherin expression levels were
      observed in both the S1P-stimulated cells and UUO mice. Nude UUO mouse kidneys
      expressed fibrotic markers. Fibrotic changes were successfully induced in both
      UUO and nude UUO mice, evident through prominent fibronectin and COL1 staining.
      These S1P-induced fibrotic changes were suppressed by FTY720 and DMS both in
      vitro and in vivo. Thus, S1P essentially and directly mediates renal fibrosis. 

PMID- 24744855
TI  - A new twist on an old idea: a two-dimensional speckle tracking assessment of
      cyclosporine as a therapeutic alternative for heart failure with preserved
      ejection fraction.
AB  - We recently reported that mitochondrial dysfunction, characterized by increased
      mitochondrial permeability transition (MPT), was present in a translational swine
      model of heart failure with preserved ejection fraction (HFpEF). Cyclophilin D is
      a key component of the MPT pore, therefore, the purpose of this study was to test
      the efficacy of a novel cyclosporine (CsA) dosing scheme as a therapeutic
      alternative for HFpEF. Computed tomography (CT), two-dimensional speckle tracking
      two-dimensional speckle tracking (2DST), and invasive hemodynamics were used to
      evaluate cardiac function. CT imaging showed 14 weeks of CsA treatment caused
      eccentric myocardial remodeling (contrasting concentric remodeling in untreated
      HF animals) and elevated systemic pressures. 2DST detected left ventricular (LV)
      mechanics associated with systolic and diastolic dysfunction prior to the onset
      of significantly increased LV end diastolic pressure including: (1) decreased
      systolic apical rotation rate, longitudinal displacement, and
      longitudinal/radial/circumferential strain; (2) decreased early diastolic
      untwisting and longitudinal strain rate; and (3) increased late diastolic
      radial/circumferential mitral strain rate. LV mechanics associated with systolic
      and diastolic impairment was enhanced to a greater extent than seen in untreated
      HF animals following CsA treatment. In conclusion, CsA treatment accelerated the
      development of heart failure, including dilatory LV remodeling and impaired
      systolic and diastolic mechanics. Although our findings do not support CsA as a
      viable therapy for HFpEF, 2DST was effective in differentiating between
      progressive gradations of developing HF and detecting diastolic impairment prior
      to the development of overt diastolic dysfunction. 

PMID- 24744856
TI  - Two cell cycle blocks caused by iron chelation of neuroblastoma cells: separating
      cell cycle events associated with each block.
AB  - Studies have presented evidence that besides the well described S phase block,
      treatment of cancer cell lines with the iron chelator deferrioxamine (DFO) also
      results in an earlier block in G1 phase. In this article, measurements of cell
      cycle regulatory proteins define this block at a very specific point in G1. DFO
      treatment results in markedly decreased cyclin A protein levels. Cyclin E levels
      that accumulate in early to mid-G1 are increased in cells treated with DFO as
      compared to the resting cells. The DFO S phase block is shown after cells are
      arrested at G1/S by (aphidicolin) then released into DFO. The same S phase block
      occurs with DFO treatment of a neuroblastoma cell line relatively resistant to
      the G1 DFO block. These experiments clearly differentiate the S phase DFO block
      from the earlier block pinpointed to a point in mid-G1, before G1/S when cyclin E
      protein increases but before increased cyclin A synthesis. Apoptosis was observed
      in cells inhibited by DFO at both cell cycle arrest points. 

PMID- 24744857
TI  - Energy cost of running and Achilles tendon stiffness in man and woman trained
      runners.
AB  - The energy cost of running (E run), a key determinant of distance running
      performance, is influenced by several factors. Although it is important to
      express E run as energy cost, no study has used this approach to compare
      similarly trained men and women. Furthermore, the relationship between Achilles
      tendon (AT) stiffness and E run has not been compared between men and women.
      Therefore, our purpose was to determine if sex-specific differences in E run
      and/or AT stiffness existed. E run (kcal kg(-1) km(-1)) was determined by
      indirect calorimetry at 75%, 85%, and 95% of the speed at lactate threshold (sLT)
      on 11 man (mean +/- SEM, 35 +/- 1 years, 177 +/- 1 cm, 78 +/- 1 kg, [Formula: see
      text]1 = 56 +/- 1 mL kg(-1) min(-1)) and 18 woman (33 +/- 1 years, 165 +/- 1 cm,
      58 +/- 1 kg, [Formula: see text]2 = 50 +/- 0.3 mL kg(-1) min(-1)) runners. AT
      stiffness was measured using ultrasound with dynamometry. Man E run was 1.01 +/-
      0.06, 1.04 +/- 0.07, and 1.07 +/- 0.07 kcal kg(-1) km(-1). Woman E run was 1.05
      +/- 0.10, 1.07 +/- 0.09, and 1.09 +/- 0.10 kcal kg(-1) km(-1). There was no
      significant sex effect for E run or RER, but both increased with speed (P < 0.01)
      expressed relative to sLT. High-range AT stiffness was 191 +/- 5.1 N mm(-1) for
      men and 125 +/- 5.5 N mm(-1), for women (P < 0.001). The relationship between low
      range AT stiffness and E run was significant at all measured speeds for women (r
      (2) = 0.198, P < 0.05), but not for the men. These results indicate that when E
      run is measured at the same relative intensity, there are no sex-specific
      differences in E run or substrate use. Furthermore, differences in E run cannot
      be explained solely by differences in AT stiffness. 

PMID- 24744858
TI  - Influence of cutaneous and muscular circulation on spatially resolved versus
      standard Beer-Lambert near-infrared spectroscopy.
AB  - The potential interference of cutaneous circulation on muscle blood volume and
      oxygenation monitoring by near-infrared spectroscopy (NIRS) remains an important
      limitation of this technique. Spatially resolved spectroscopy (SRS) was reported
      to minimize the contribution of superficial tissue layers in cerebral monitoring
      but this characteristic has never been documented in muscle tissue monitoring.
      This study aims to compare SRS with the standard Beer-Lambert (BL) technique in
      detecting blood volume changes selectively induced in muscle and skin. In 16
      healthy subjects, the biceps brachii was investigated during isometric elbow
      flexion at 70% of the maximum voluntary contractions lasting 10 sec, performed
      before and after exposure of the upper arm to warm air flow. From probes applied
      over the muscle belly the following variables were recorded: total hemoglobin
      index (THI, SRS-based), total hemoglobin concentration (tHb, BL-based), tissue
      oxygenation index (TOI, SRS-based), and skin blood flow (SBF), using laser
      Doppler flowmetry. Blood volume indices exhibited similar changes during muscle
      contraction but only tHb significantly increased during warming (+5.2 +/- 0.7
      MUmol/L.cm, an effect comparable to the increase occurring in postcontraction
      hyperemia), accompanying a 10-fold increase in SBF. Contraction-induced changes
      in tHb and THI were not substantially affected by warming, although the tHb
      tracing was shifted upward by (5.2 +/- 3.5 MUmol/L.cm, P < 0.01). TOI was not
      affected by cutaneous warming. In conclusion, SRS appears to effectively reject
      interference by SBF in both muscle blood volume and oxygenation monitoring.
      Instead, BL-based parameters should be interpreted with caution, whenever changes
      in cutaneous perfusion cannot be excluded. 

PMID- 24744859
TI  - Forearm vascular responses to mental stress in healthy older adults.
AB  - Forearm vascular conductance (FVC) increases in response to mental stress (verbal
      mental arithmetic) in young people. However, the effect of healthy aging and
      mental stress on FVC is unknown. In this study, we tested the hypothesis that FVC
      and cutaneous vascular conductance (CVC) would be attenuated in older adults
      compared to young adults. In 13 young (27 +/- 1 year) and 11 older (62 +/- 1
      year) subjects, we quantified heart rate (HR), mean arterial pressure (MAP), FVC
      (Doppler ultrasound), and CVC (laser Doppler flowmetry) in response to a 3-min
      bout of mental stress in the supine posture. Changes from baseline were compared
      between groups and physiological variables were also correlated. Older adults had
      a blunted HR response to mental stress (Delta = 7 +/- 2 vs. 14 +/- 2 beats/min)
      but DeltaMAP was comparable between groups (Delta = 11 +/- 2 mmHg vs. 9 +/- 1).
      During the third minute of mental stress, the %DeltaFVC (-2 +/- 5 vs. 31 +/- 12%)
      and %DeltaCVC (2 +/- 6 vs. 31 +/- 15%) were both impaired in older adults
      compared to young subjects. There was no relationship between DeltaHR and
      %DeltaCVC in either group, but there was a positive relationship between DeltaHR
      and %DeltaFVC in both young subjects (R = 0.610, P < 0.027) and older subjects (R
      = 0.615, P < 0.044), such that larger tachycardia was associated with higher
      forearm vasodilation. These data indicate that older adults have impaired forearm
      vasodilation in response to mental stress. 

PMID- 24744860
TI  - Differential effects of Smad3 targeting in a murine model of chronic kidney
      disease.
AB  - Transforming growth factor (TGF)-beta1 has a pivotal role in the pathogenesis of
      progressive kidney diseases that are characterized by fibrosis. The main
      intracellular signaling pathway of TGF-beta1 is the Smad system, where Smad2 and
      Smad3 play a central role in transcriptional regulation of target genes involved
      in extracellular matrix (ECM) metabolism. This study analyzes the hypothesis that
      blockade of Smad3 attenuates the development of TGF-beta1-driven renal fibrosis.
      This was examined in vivo in a transgenic model of TGF-beta1-induced chronic
      kidney disease with Smad3 or without Smad3 expression and in vitro in mesangial
      cells and glomerular endothelial cells with Smad2/3 inhibitors or Smad3
      knockdown. Electron microscopy was used for evaluation of morphological changes,
      real-time polymerase chain reaction for detection of RNA expression, and
      immunohistochemistry for localization of ECM components. Matrix metalloproteinase
      (MMP) level was assessed by gelatin zymography electrophoresis and located by in
      situ zymography. The results show TGF-beta1-induced mesangial matrix expansion,
      tubulointerstitial fibrosis, and tubular basement membrane thickening that are
      attenuated by Smad3 deletion, whereas TGF-beta1-induced glomerular basement
      membrane thickening is not shown. The amount and distribution profile of MMP-2
      may suggest a role of the enzyme herein. We conclude that Smad3 targeting is not
      exclusively beneficial as Smad3 has diverse transcriptional regulatory effects in
      different cell types in the kidney. 

PMID- 24744861
TI  - Novel features on the regulation by mitochondria of calcium and secretion
      transients in chromaffin cells challenged with acetylcholine at 37 degrees C.
AB  - From experiments performed at room temperature, we know that the buffering of
      Ca(2+) by mitochondria contributes to the shaping of the bulk cytosolic calcium
      transient ([Ca(2+)]c) and secretion transients of chromaffin cells stimulated
      with depolarizing pulses. We also know that the mitochondrial Ca(2+) transporters
      and the release of catecholamine are faster at 37 degrees C with respect to room
      temperature. Therefore, we planned this investigation to gain further insight
      into the contribution of mitochondrial Ca(2+) buffering to the shaping of
      [Ca(2+)]c and catecholamine release transients, using some novel experimental
      conditions that have not been yet explored namely: (1) perifusion of bovine
      chromaffin cells (BCCs) with saline at 37 degrees C and their repeated
      challenging with the physiological neurotransmitter acetylcholine (ACh); (2)
      separate blockade of mitochondrial Ca(2+) uniporter (mCUP) with Ru360 or the
      mitochondrial Na(+)/Ca(2+) exchanger (mNCX) with CGP37157; (3) full blockade of
      the mitochondrial Ca(2+) cycling (mCC) by the simultaneous inhibition of the mCUP
      and the mNCX. Ru360 caused a pronounced delay of [Ca(2+)]c clearance and
      augmented secretion. In contrast, CGP37157 only caused a tiny delay of [Ca(2+)]c
      clearance and a mild decrease in secretion. The mCC resulting in continued Ca(2+)
      uptake and its release back into the cytosol was interrupted by combined Ru360 +
      CGP37157 (Ru/CGP), the protonophore carbonyl cyanide-p
      trifluoromethoxyphenylhydrazone, or combined oligomycin + rotenone (O/R); these
      three treatments caused a mild but sustained elevation of basal [Ca(2+)]c that,
      however, was not accompanied by a parallel increase in basal secretion.
      Nevertheless, all treatments caused a pronounced augmentation of ACh-induced
      secretion, with minor changes of the ACh-induced [Ca(2+)]c transients. Combined
      Ru/CGP did not alter the resting membrane potential in current-clamped cells.
      Additionally, Ru/CGP did not increase basal [Ca(2+)]c near subplasmalemmal sites
      and caused a mild decrease in the size of the readily releasable vesicle pool.
      Our results provide new functional features in support of the view that in BCCs
      there are two subpopulations of mitochondria, M1 underneath the plasmalemma
      nearby exocytotic sites and M2 at the core cell nearby vesicle transport sites.
      While M1 serves to shape the ACh-elicited exocytotic response through its
      efficient Ca(2+) removal by the mCUP, M2 shapes the lower [Ca(2+)]c elevations
      required for new vesicle supply to the exocytotic machinery, from the large
      reserve vesicle pool at the cell core. The mCUP of the M1 pool seems to play a
      more prominent role in controlling the ACh responses, in comparison with the
      mNCX. 

PMID- 24744862
TI  - Progressive right ventricular functional and structural changes in a mouse model
      of pulmonary arterial hypertension.
AB  - Right ventricle (RV) dysfunction occurs with progression of pulmonary arterial
      hypertension (PAH) due to persistently elevated ventricular afterload. A critical
      knowledge gap is the molecular mechanisms that govern the transition from RV
      adaptation to RV maladaptation, which leads to failure. Here, we hypothesize that
      the recently established mouse model of PAH, via hypoxia and SU5416 treatment
      (HySu), captures that transition from adaptive to maladaptive RV remodeling
      including impairments in RV function and decreases in the efficiency of RV
      interactions with the pulmonary vasculature. To test this hypothesis, we exposed
      C57BL6 male mice to 0 (control), 14, 21, and 28 days of HySu and then obtained
      synchronized RV pressure and volume measurements in vivo. With increasing HySu
      exposure duration, arterial afterload increased monotonically, leading to a
      continuous increase in RV stroke work, RV fibrosis, and RV wall stiffening (P <
      0.05). RV contractility increased at 14 days of HySu exposure and then plateaued
      (P < 0.05). As a result, ventricular-vascular coupling efficiency tended to
      increase at 14 days and then decrease. Our results suggest that RV remodeling may
      begin to shift from adaptive to maladaptive with increasing duration of HySu
      exposure, which would mimic changes in RV function with PAH progression found
      clinically. However, for the duration of HySu exposure used here, no drop in
      cardiac output was found. We conclude that the establishment of a mouse model for
      overt RV failure due to PAH remains an important task. 

PMID- 24744863
TI  - Modulatory role of androgenic and estrogenic neurosteroids in determining the
      direction of synaptic plasticity in the CA1 hippocampal region of male rats.
AB  - Estrogenic and androgenic neurosteroids can rapidly modulate synaptic plasticity
      in the brain through interaction with membrane receptors for estrogens (ERs) and
      androgens (ARs). We used electrophysiological recordings in slices of young and
      adolescent male rats to explore the influence of sex neurosteroids on synaptic
      plasticity in the CA1 hippocampal region, by blocking ARs or ERs during induction
      of long-term depression (LTD) and depotentiation (DP) by low-frequency
      stimulation (LFS) and long-term potentiation (LTP) by high-frequency stimulation
      (HFS). We found that LTD and DP depend on ARs, while LTP on ERs in both age
      groups. Accordingly, the AR blocker flutamide affected induction of LTD reverting
      it into LTP, and prevented DP, while having no effect on HFS-dependent LTP.
      Conversely, ER blockade with ICI 182,780 (ICI) markedly reduced LTP, but did not
      influence LTD and DP. However, the receptor blockade did not affect the
      maintenance of either LTD or LTP. Moreover, we found that similar to LTP and LTD
      induced in control condition, the LTP unveiled by flutamide during LFS and
      residual LTP induced by HFS under ICI depended on N-methyl-d aspartate receptor
      (NMDAR) activation. Furthermore, as the synaptic paired-pulse facilitation (PPF)
      was not affected by either AR or ER blockade, we suggest that sex neurosteroids
      act primarily at a postsynaptic level. This study demonstrates for the first time
      the crucial role of estrogenic and androgenic neurosteroids in determining the
      sign of hippocampal synaptic plasticity in male rat and the activity-dependent
      recruitment of androgenic and estrogenic pathways leading to LTD and LTP,
      respectively. 

PMID- 24744864
TI  - Voltage-dependent potassium currents expressed in Xenopus laevis oocytes after
      injection of mRNA isolated from trophozoites of Giardia lamblia (strain Portland
      1).
AB  - Despite its importance as a health problem issue, almost nothing is known about
      the membrane physiology of Giardia lamblia and practically there exist no
      information so far regarding the variety and properties of ion channels that this
      protozoan parasite possesses. To address this subject we resorted to an indirect
      method, consisting in the injection of mRNA and further characterization of ion
      currents in Xenopus oocytes. In this work, we show that oocytes injected with
      mRNA isolated from cultured trophozoites of G. lamblia, strain Portland-1 express
      novel potassium currents that appear over the second day after injection and show
      time- and voltage-dependent activation followed by a slow inactivation. They
      start activating at -90 mV, with V1/2 of -30 mV; its time constant of activation
      (at +60 mV) is 0.11 sec, whereas that of inactivation is 1.92 sec, V1/2 = -44.6
      mV. Such K currents were effectively blocked by K channel blockers TEA and 4AP,
      as well as Ba(2+), quinine, quinidine, charybdotoxin, dendrotoxin-1, capsaicin,
      margatoxin, and diltiazem. These results suggest that such currents are the
      result of expression of Giardia's voltage-gated K channels heterologously
      expressed in Xenopus laevis oocytes. 

PMID- 24744865
TI  - Heritability of motor control and motor learning.
AB  - The aim of this study was to elucidate the relative contribution of genes and
      environment on individual differences in motor control and acquisition of a force
      control task, in view of recent association studies showing that several
      candidate polymorphisms may have an effect on them. Forty-four healthy female
      twins performed brisk isometric abductions with their right thumb. Force was
      recorded by a transducer and fed back to the subject on a computer screen. The
      task was to place the tracing of the peak force in a force window defined between
      30% and 40% of the subject's maximum force, as determined beforehand. The initial
      level of proficiency was defined as the number of attempts reaching the force
      window criterion within the first 100 trials. The difference between the number
      of successful trials within the last and the first 100 trials was taken as a
      measure of motor learning. For motor control, defined by the initial level of
      proficiency, the intrapair differences in monozygotic (MZ) and dizygotic (DZ)
      twins were 6.8 +/- 7.8 and 13.8 +/- 8.4, and the intrapair correlations 0.77 and
      0.39, respectively. Heritability was estimated at 0.68. Likewise for motor
      learning intrapair differences in the increment of the number of successful
      trials in MZ and DZ twins were 5.4 +/- 5.2 and 12.8 +/- 7, and the intrapair
      correlations 0.58 and 0.19. Heritability reached 0.70. The present findings
      suggest that heredity accounts for a major part of existing differences in motor
      control and motor learning, but uncertainty remains which gene polymorphisms may
      be responsible. 

PMID- 24744866
TI  - Evidence for a prosurvival role of alpha-7 nicotinic acetylcholine receptor in
      alternatively (M2)-activated macrophages.
AB  - Recent observations in endothelial cells and macrophages indicate that nicotinic
      acetylcholine receptors (nAChRs) are potential novel players in mechanisms linked
      to atherogenesis. In macrophages, alpha7nAChR mediates anti-inflammatory actions
      and contributes to regulation of cholesterol flux and phagocytosis. Considering
      that macrophage apoptosis is a key process throughout all stages of
      atherosclerotic lesion development, in the present study, we examined for the
      first time the impact of alpha7nAChR expression and function in macrophage
      survival and apoptosis using in vitro polarized (M1 and M2) bone marrow-derived
      macrophages (BMDMs) from wild-type and alpha7nAChR knockout mice. Our findings
      show that stimulation of alpha7nAChR results in activation of the STAT3
      prosurvival pathway and protection of macrophages from endoplasmic reticulum (ER)
      stress-induced apoptosis. These actions are rather selective for M2 BMDMs and are
      associated to activation of the JAK2/STAT3 axis. Remarkably, these effects are
      completely lost in M2 macrophages lacking alpha7nAChR. 

PMID- 24744867
TI  - Thrombin-mediated activation of Akt signaling contributes to pulmonary vascular
      remodeling in pulmonary hypertension.
AB  - Chronic thromboembolic pulmonary hypertension (CTEPH) has been increasingly
      recognized as a common source of elevated pulmonary vascular resistance and
      pulmonary hypertension. It is clear that development of pulmonary thromboemboli
      is the inciting event for this process, yet it remains unclear why some patients
      have persistent pulmonary artery occlusion leading to distal pulmonary vascular
      remodeling and CTEPH. Thrombin, a serine protease, is an integral part of the
      common coagulation cascade, yet thrombin also has direct cellular effects through
      interaction with the family of PAR membrane receptors. This study is designed to
      determine the effects of thrombin on Akt signaling in pulmonary artery smooth
      muscle cells (PASMC) from normal humans and pulmonary hypertension patients.
      Thrombin treatment of PASMC resulted in a transient increase in Akt
      phosphorylation and had similar effects on the downstream targets of the Akt/mTOR
      pathway. Ca(2+) is shown to be required for Akt phosphorylation as well as serum
      starvation, a distinct effect compared to platelet-derived growth factor.
      Thrombin treatment was associated with a rise in intracellular [Ca(2+)] and
      enhanced store-operated calcium entry (SOCE). These effects lead to enhanced
      proliferation, which is more dramatic in both IPAH and CTEPH PASMC. Enhanced
      proliferation is also shown to be attenuated by inhibition of Akt/mTOR in CTEPH
      PASMC. Thrombin has direct effects on PASMC increasing intracellular [Ca(2+)] and
      PASMC proliferation, an effect attributed to Akt phosphorylation. The current
      results implicate the effects of thrombin in the pathogenesis of idiopathic
      pulmonary arterial hypertension (IPAH) and CTEPH, which may potentially be a
      novel therapeutic target. 

PMID- 24744868
TI  - Effects of gravitational loading levels on protein expression related to
      metabolic and/or morphologic properties of mouse neck muscles.
AB  - The effects of 3 months of spaceflight (SF), hindlimb suspension, or exposure to
      2G on the characteristics of neck muscle in mice were studied. Three 8-week-old
      male C57BL/10J wild-type mice were exposed to microgravity on the International
      Space Station in mouse drawer system (MDS) project, although only one mouse
      returned to the Earth alive. Housing of mice in a small MDS cage (11.6 * 9.8-cm
      and 8.4-cm height) and/or in a regular vivarium cage was also performed as the
      ground controls. Furthermore, ground-based hindlimb suspension and 2G exposure by
      using animal centrifuge (n = 5 each group) were performed. SF-related shift of
      fiber phenotype from type I to II and atrophy of type I fibers were noted. Shift
      of fiber phenotype was related to downregulation of mitochondrial proteins and
      upregulation of glycolytic proteins, suggesting a shift from oxidative to
      glycolytic metabolism. The responses of proteins related to calcium handling,
      myofibrillar structure, and heat stress were also closely related to the shift of
      muscular properties toward fast-twitch type. Surprisingly, responses of proteins
      to 2G exposure and hindlimb suspension were similar to SF, although the shift of
      fiber types and atrophy were not statistically significant. These phenomena may
      be related to the behavior of mice that the relaxed posture without lifting their
      head up was maintained after about 2 weeks. It was suggested that inhibition of
      normal muscular activities associated with gravitational unloading causes
      significant changes in the protein expression related to metabolic and/or
      morphological properties in mouse neck muscle. 

PMID- 24744869
TI  - Gastric emptying and duodenal motility upon intake of a liquid meal with
      monosodium glutamate in healthy subjects.
AB  - Glutamate is thought to serve as a special signal for gut functions. We
      investigated the effects of monosodium l-glutamate (MSG) on gastric emptying and
      duodenal motility. Ten healthy male volunteers underwent rapid magnetic resonance
      imaging (MRI) of the abdomen. Coronal images were successively acquired after
      ingestion of liquid meal (200 kcal in 200 mL: 9 g protein, 28.4 g carbohydrate,
      5.6 g fat, 370 mg Na(+)) with and without 0.5% MSG. During the acquisition of
      MRI, participants breathed freely. In all participants, the gastric residual
      volume gradually decreased to 80.1 +/- 14.2% without MSG and to 75.9 +/- 14.3%
      with MSG after 60 min (P = 0.45 between the groups, n = 10). In two of 10
      participants, gastric emptying slowed down significantly, whereas in the
      remaining eight participants, gastric residual volume decreased to 84.0 +/- 13.1%
      without MSG, and to 73.0 +/- 14.6% with MSG after 60 min (P = 0.015, n = 8).
      There was no difference in the shape of the stomach between groups. In four of
      the eight participants responding positively to MSG, the duodenum wall was
      sufficiently identified to quantify the motions. The inclusion of MSG enhanced
      duodenal motility, judging from changes in (1) the magnitude of the duodenal
      area, (2) the center of gravity, and (3) the mean velocity of the wall motions.
      The third parameter most significantly indicated the excitatory effect of l
      glutamate on duodenum motility (~ three- to sevenfold increase during 60 min, P <
      0.05, n = 4). These results suggest that MSG accelerates gastric emptying by
      facilitating duodenal motility, at least in subjects with positive responses to
      MSG. 

PMID- 24744870
TI  - Roles of the subfornical organ and area postrema in arterial pressure increases
      induced by 48-h water deprivation in normal rats.
AB  - In rats, water deprivation (WD) increases arterial blood pressure (BP) in part
      due to actions of elevated osmolality in the brain to increase vasopressin levels
      and sympathetic activity. However, the osmoreceptors that mediate this response
      have not been identified. To test the hypothesis that osmoregulatory
      circumventricular organs are involved, BP and heart rate (HR) were continuously
      recorded telemetrically during 48 h of WD in normal rats with lesions (x) or sham
      lesions (sham) of the subfornical organ (SFO) or area postrema (AP). Although WD
      increased BP in SFOx and SFOsham rats, no significant difference in the
      hypertensive response was observed between groups. HR decreased transiently but
      similarly in SFOx and SFOsham rats during the first 24 h of WD. When water was
      reintroduced, BP and HR decreased rapidly and similarly in both groups. BP
      (during lights off) and HR were both lower in APx rats before WD compared to
      APsham. WD increased BP less in APx rats, and the transient bradycardia was
      eliminated. Upon reintroduction of drinking water, smaller falls in both BP and
      HR were observed in APx rats compared to APsham rats. WD increased plasma
      osmolality and vasopressin levels similarly in APx and APsham rats, and acute
      blockade of systemic V1 vasopressin receptors elicited similar depressor
      responses, suggesting that the attenuated BP response is not due to smaller
      increases in vasopressin or osmolality. In conclusion, the AP, but not the SFO,
      is required for the maximal hypertensive effect induced by WD in rats. 

PMID- 24744871
TI  - Combined reflectance spectroscopy and stochastic modeling approach for
      noninvasive hemoglobin determination via palpebral conjunctiva.
AB  - A combination of stochastic photon propagation model in a multilayered human
      eyelid tissue and reflectance spectroscopy was used to study palpebral
      conjunctiva spectral reflectance for hemoglobin (Hgb) determination. The
      developed model is the first biologically relevant model of eyelid tissue, which
      was shown to provide very good approximation to the measured spectra. Tissue
      optical parameters were defined using previous histological and microscopy
      studies of a human eyelid. After calibration of the model parameters the
      responses of reflectance spectra to Hgb level and blood oxygenation variations
      were calculated. The stimulated reflectance spectra in adults with normal and low
      Hgb levels agreed well with experimental data for Hgb concentrations from 8.1 to
      16.7 g/dL. The extracted Hgb levels were compared with in vitro Hgb measurements.
      The root mean square error of cross-validation was 1.64 g/dL. The method was
      shown to provide 86% sensitivity estimates for clinically diagnosed anemia cases.
      A combination of the model with spectroscopy measurements provides a new tool for
      noninvasive study of human conjunctiva to aid in diagnosing blood disorders such
      as anemia. 

PMID- 24744872
TI  - Acute impact of retrograde shear rate on brachial and superficial femoral artery
      flow-mediated dilation in humans.
AB  - Retrograde shear rate (SR) in the brachial artery (BA) is associated with
      endothelial dysfunction; a precursor to atherosclerosis. The BA does not
      typically manifest clinical atherosclerosis, whereas the superficial femoral
      artery (SFA) is more prone to developing plaque. Examine whether the impact of
      incremental levels of retrograde SR differs between atherosclerosis-prone (i.e.,
      SFA) and -resistant vessels (i.e., BA) in healthy men. Thirteen healthy young men
      reported three times to the laboratory. We examined BA flow-mediated dilation
      (FMD) before and after 30-min exposure to cuff inflation around the forearm at 0,
      30, and 60 mmHg, to manipulate retrograde SR. Subsequently, the 30-min
      intervention was repeated in the SFA, using the same cuff pressure as in the
      forearm. Order of testing (vessel and intervention) was randomized among
      subjects. We found a dose-dependent increase in retrograde SR with 30 and 60 mmHg
      cuff inflation, which was present in both the BA and SFA (all P < 0.05). BA and
      SFA FMD decreased after the 30-min intervention ("time": P = 0.012), and this was
      dependent on cuff pressure ("cuff * time": P = 0.024). A significant decrease in
      FMD was observed after 60 mmHg only and this change was similarly present in both
      arteries ("time * artery": P = 0.227). Moreover, the BA and SFA demonstrate a
      similar relationship between changes in retrograde SR and FMD (r = 0.498 and
      0.475, respectively). Our study demonstrates that acute exposure to an increase
      in retrograde shear leads to comparable decreases in FMD in atherosclerotic-prone
      and -resistant conduit arteries in humans. 

PMID- 24744873
TI  - Early impairment of skeletal muscle endothelial glycocalyx barrier properties in
      diet-induced obesity in mice.
AB  - While previous studies have indicated an important role for the endothelial
      glycocalyx in regulation of microvascular function, it was recently shown that
      acute enzymatic glycocalyx degradation in rats was associated with an impaired
      insulin-mediated glucose disposal. The aim of this study was to determine whether
      glycocalyx damage in skeletal muscle occurs at an early stage of diet-induced
      obesity (DIO). The microcirculation of the hindlimb muscle of anesthetized
      C57Bl/6 mice, fed chow (CON) or a high-fat diet (HFD) for 6 and 18 weeks (w),
      respectively, was visualized with a Sidestream Dark-Field camera, and glycocalyx
      barrier properties were derived from the calculated perfused boundary region
      (PBR). Subsequently, an intraperitoneal glucose tolerance test was performed and
      the area under the curve (AUC) of blood glucose was calculated. Impairment of
      glycocalyx barrier properties was already apparent after 6 weeks of HFD and
      remained after 18 weeks of HFD (PBR [in MUm]: 0.81 +/- 0.03 in CON_6w vs. 0.97 +/
      0.04 in HFD_6w and 1.02 +/- 0.07 in HFD_18w [both P < 0.05]). Glucose
      intolerance appeared to develop more slowly (AUC [in mmol/L * 120 min]: 989 +/-
      61 in CON_6w vs. 1204 +/- 89 in HFD_6w [P = 0.11] and 1468 +/- 84 in HFD_18w [P <
      0.05]) than the impairment of glycocalyx barrier properties. The data indicate
      that damage to the endothelial glycocalyx is an early event in DIO. It is
      suggested that glycocalyx damage may contribute to the development of insulin
      resistance in obesity. 

PMID- 24744874
TI  - Effects of ATP7A overexpression in mice on copper transport and metabolism in
      lactation and gestation.
AB  - Placentae and mammary epithelial cells are unusual in robustly expressing two
      copper "pumps", ATP7A and B, raising the question of their individual roles in
      these tissues in pregnancy and lactation. Confocal microscopic evidence locates
      ATP7A to the fetal side of syncytiotrophoblasts, suggesting a role in pumping Cu
      towards the fetus; and to the basolateral (blood) side of lactating mammary
      epithelial cells, suggesting a role in recycling Cu to the blood. We tested these
      concepts in wild-type C57BL6 mice and their transgenic counterparts that
      expressed hATP7A at levels 10-20* those of endogenous mAtp7a. In lactation,
      overexpression of ATP7A reduced the Cu concentrations of the mammary gland and
      milk ~50%. Rates of transfer of tracer (64)Cu to the suckling pups were similarly
      reduced over 30-48 h, as was the total Cu in 10-day -old pups. During the early
      and middle periods of gestation, the transgenic litters had higher Cu
      concentrations than the wild-type, placental Cu showing the reverse trend; but
      this difference was lost by the first postnatal day. The transgenic mice
      expressed ATP7A in some hepatocytes, so we investigated the possibility that
      metalation of ceruloplasmin (Cp) might be enhanced. Rates of (64)Cu incorporation
      into Cp, oxidase activity, and ratios of holo to apoceruloplasmin were unchanged.
      We conclude that in the lactating mammary gland, the role of ATP7A is to return
      Cu to the blood, while in the placenta it mediates Cu delivery to the fetus and
      is the rate-limiting step for fetal Cu nutrition during most of gestation in
      mice. 

PMID- 24744875
TI  - Absence of calcium-independent phospholipase A2 beta impairs platelet-activating
      factor production and inflammatory cell recruitment in Trypanosoma cruzi-infected
      endothelial cells.
AB  - Both acute and chronic phases of Trypanosoma cruzi (T. cruzi) infection are
      characterized by tissue inflammation, mainly in the heart. A key step in the
      inflammatory process is the transmigration of inflammatory cells across the
      endothelium to underlying infected tissues. We observed increased arachidonic
      acid release and platelet-activating factor (PAF) production in human coronary
      artery endothelial cells (HCAEC) at up to 96 h of T. cruzi infection. Arachidonic
      acid release is mediated by activation of the calcium-independent phospholipase
      A2 (iPLA2) isoforms iPLA2 beta and iPLA2 gamma, whereas PAF production was
      dependent upon iPLA2 beta activation alone. Trypanosoma cruzi infection also
      resulted in increased cell surface expression of adhesion molecules. Increased
      adherence of inflammatory cells to T. cruzi-infected endothelium was blocked by
      inhibition of endothelial cell iPLA2 beta or by blocking the PAF receptor on
      inflammatory cells. This suggests that PAF, in combination with adhesion
      molecules, might contribute to parasite clearing in the heart by recruiting
      inflammatory cells to the endothelium. 

PMID- 24744876
TI  - Possible involvement of IGF-1 signaling on compensatory growth of the
      infraspinatus muscle induced by the supraspinatus tendon detachment of rat
      shoulder.
AB  - A rotator cuff tear (RCT) is a common musculoskeletal disorder among elderly
      people. RCT is often treated conservatively for functional compensation by the
      remaining muscles. However, the mode of such compensation after RCT has not yet
      been fully understood. Here, we used the RCT rat model to investigate the
      compensatory process in the remaining muscles. The involvement of insulin-like
      growth factor 1 (IGF-1)/Akt signaling which potentially contributes to the muscle
      growth was also examined. The RCT made by transecting the supraspinatus (SSP)
      tendon resulted in atrophy of the SSP muscle. The remaining infraspinatus (ISP)
      muscle weight increased rapidly after a transient decrease (3 days), which could
      be induced by posttraumatic immobilization. The IGF-1 mRNA levels increased
      transiently at 7 days followed by a gradual increase thereafter in the ISP
      muscle, and those of IGF-1 receptor mRNA significantly increased after 3 days.
      IGF-1 protein levels biphasically increased (3 and 14 days), then gradually
      decreased thereafter. The IGF-1 protein levels tended to show a negative
      correlation with IGF-1 mRNA levels. These levels also showed a negative
      correlation with the ISP muscle weight, indicating that the increase in IGF-1
      secretion may contribute to the ISP muscle growth. The pAkt/Akt protein ratio
      decreased transiently by 14 days, but recovered later. The IGF-1 protein levels
      were negatively correlated with the pAkt/Akt ratio. These results indicate that
      transection of the SSP tendon activates IGF-1/Akt signaling in the remaining ISP
      muscle for structural compensation. Thus, the remaining muscles after RCT can be
      a target for rehabilitation through the activation of IGF-1/Akt signaling. 

PMID- 24744877
TI  - Effect of hypoxic training on inflammatory and metabolic risk factors: a
      crossover study in healthy subjects.
AB  - The purpose of this study was to investigate the influence of hypoxic physical
      exercise on metabolic syndrome (MS) risk markers and high-sensitivity C-reactive
      protein (CRP) and to compare its effects on preperitoneal fat, arterial
      stiffness, and several blood parameters related to MS to those of a control group
      who trained under normoxic conditions. Fourteen healthy men were examined.
      Participants performed treadmill exercise 3 days per week for 4 weeks, under
      either normobaric hypoxic or normobaric normoxic conditions, for 50 min
      (including a 5-min warm-up and 5-min cool down) after a 30-min rest period.
      Exercise was performed at a heart rate (HR) corresponding to 60% of the HR at
      each individual's maximum oxygen uptake. Training under the different
      environmental conditions was performed 4 months apart to ensure a sufficient
      washout period. Waist circumference, preperitoneal fat thickness, brachial-ankle
      pulse wave velocity, and high-sensitivity CRP after training were significantly
      lower in the hypoxic group than in the normoxic group. Our results suggest that
      regular short-term hypoxic training may more effectively reduce arterial
      stiffness, and thus prevent arteriosclerosis, compared to training performed at a
      similar exercise intensity under normoxic conditions. 

PMID- 24744878
TI  - Characterization of blood pressure and endothelial function in TRPV4-deficient
      mice with l-NAME- and angiotensin II-induced hypertension.
AB  - Transient receptor potential vanilloid type 4 (TRPV4) is an endothelial Ca(2+)
      entry channel contributing to endothelium-mediated dilation in conduit and
      resistance arteries. We investigated the role of TRPV4 in the regulation of blood
      pressure and endothelial function under hypertensive conditions. TRPV4-deficient
      (TRPV4(-/-)) and wild-type (WT) control mice were given l-NAME (0.5 g/L) in
      drinking water for 7 days or subcutaneously infused with angiotensin (Ang) II
      (600 ng/kg per minute) for 14 days, and blood pressure measured by
      radiotelemetry. TRPV4(-/-) mice had a lower baseline mean arterial pressure (MAP)
      (12-h daytime MAP, 94 +/- 2 vs. 99 +/- 2 mmHg in WT controls). l-NAME treatment
      induced a slightly greater increase in MAP in TRPV4(-/-) mice (day 7, 13 +/- 4%)
      compared to WT controls (6 +/- 2%), but Ang II-induced increases in MAP were
      similar in TRPV4(-/-) and WT mice (day 14, 53 +/- 6% and 37 +/- 11%,
      respectively, P < 0.05). Chronic infusion of WT mice with Ang II reduced both
      acetylcholine (ACh)-induced dilation (dilation to 10(-5) mol/L ACh, 71 +/- 5% vs.
      92 +/- 2% of controls) and the TRPV4 agonist GSK1016790A-induced dilation of
      small mesenteric arteries (10(-8) mol/L GSK1016790A, 14 +/- 5% vs. 77 +/- 7% of
      controls). However, Ang II treatment did not affect ACh dilation in TRPV4(-/-)
      mice. Mechanistically, Ang II did not significantly alter either TRPV4 total
      protein expression in mesenteric arteries or TRPV4 agonist-induced Ca(2+)
      response in mesenteric endothelial cells in situ. These results suggest that
      TRPV4 channels play a minor role in blood pressure regulation in l-NAME- but not
      Ang II-induced hypertension, but may be importantly involved in Ang II-induced
      endothelial dysfunction. 

PMID- 24744879
TI  - A high-calcium diet failed to rescue an osteopenia phenotype in claudin-18
      knockout mice.
AB  - We have recently demonstrated that mice with disruption of claudin-18 (Cldn-18)
      gene exhibited osteopenia due to increased bone resorption (BR). In this study,
      we found that gastric pH was significantly higher in Cldn-18 knockout (KO) mice
      compared to heterozygous control mice at 10 weeks of age. To test the possibility
      that the increased BR in the Cldn-18 KO mice fed a normal-Ca diet is a
      consequence of decreased Ca absorption caused by increased stomach pH, we
      subjected KO and control mice to a normal-Ca and high-Ca diet at birth. Serum Ca
      levels were significantly lower in Cldn-18 KO mice compared to control mice at a
      normal-Ca diet but not at high-Ca diet. Dual energy X-ray absorptiometry revealed
      that a high-Ca diet significantly increased lumbar bone mineral density (BMD),
      but had no effect on femur/tibia BMD in both Cldn-18 KO and control mice compared
      to a normal-Ca diet. While a high-Ca diet did not affect volumetric BMD,
      trabecular, and cortical parameters of the lumbar vertebra (LV) as measured by
      MUCT, the size of the LV did increase, in both genotypes due to reduced BR.
      Comparison of the skeletal phenotype of high-Ca Cldn-18 KO and control mice
      revealed that an osteopenia phenotype seen at a normal-Ca diet was still
      maintained at different skeletal sites in the KO mice till 10 weeks of age. In
      conclusion, our findings suggest that increased BR is likely caused by direct
      effects of a lack of Cldn-18 on osteoclasts rather than gastric pH changes. 

PMID- 24744880
TI  - Amiloride-sensitive fluid resorption in NCI-H441 lung epithelia depends on an
      apical Cl(-) conductance.
AB  - Proper apical airway surface hydration is essential to maintain lung function.
      This hydration depends on well-balanced water resorption and secretion. The
      mechanisms involved in resorption are still a matter of debate, especially as the
      measurement of transepithelial water transport remains challenging. In this
      study, we combined classical short circuit current (I SC) measurements with a
      novel D2O dilution method to correlate ion and water transport in order to reveal
      basic transport mechanisms in lung epithelia. D2O dilution method enabled precise
      analysis of water resorption with an unprecedented resolution. NCI-H441 cells
      cultured at an air-liquid interface resorbed water at a rate of 1.5 +/- 0.4
      MUL/(h cm(2)). Water resorption and I SC were reduced by almost 80% in the
      presence of the bulk Cl(-) channel inhibitor 5-nitro-2-(3
      phenylpropylamino)benzoic acid (NPPB) or amiloride, a specific inhibitor of
      epithelial sodium channel (ENaC). However, water resorption and I SC were only
      moderately affected by forskolin or cystic fibrosis transmembrane regulator
      (CFTR) channel inhibitors (CFTRinh-172 and glybenclamide). In line with previous
      studies, we demonstrate that water resorption depends on ENaC, and CFTR channels
      have only a minor but probably modulating effect on water resorption. However,
      the major ENaC-mediated water resorption depends on an apical non-CFTR Cl(-)
      conductance. 

PMID- 24744881
TI  - Lithium induces microcysts and polyuria in adolescent rat kidney independent of
      cyclooxygenase-2.
AB  - In patients, chronic treatment with lithium leads to renal microcysts and
      nephrogenic diabetes insipidus (NDI). It was hypothesized that renal
      cyclooxygenase-2 (COX-2) activity promotes microcyst formation and NDI. Kidney
      microcysts were induced in male adolescent rats by feeding dams with lithium (50
      mmol/kg chow) from postnatal days 7-34. Lithium treatment induced somatic growth
      retardation, renal microcysts and dilatations in cortical collecting duct; it
      increased cortical cell proliferation and inactive pGSK-3beta abundance; it
      lowered aquaporin-2 (AQP2) protein abundance and induced polyuria with decreased
      ability to concentrate the urine; and it increased COX-2 protein level in thick
      ascending limb. Concomitant treatment with lithium and a specific COX-2
      inhibitor, parecoxib (5 mg/kg per day, P10-P34), did not prevent lithium-induced
      microcysts and polyuria, but improved urine concentrating ability transiently
      after a 1-desamino-8-D-arginine vasopressin challenge. COX-2 inhibition did not
      reduce cortical lithium-induced cell proliferation and phosphorylation of
      glycogen synthase kinase-3beta (GSK-3beta). COX-1 protein abundance increased in
      rat kidney cortex in response to lithium. COX-1 immunoreactivity was found in
      microcyst epithelium in rat kidney. A human nephrectomy specimen from a patient
      treated for 28 years with lithium displayed multiple, COX-1-immunopositive,
      microcysts. In chronic lithium-treated adolescent rats, COX-2 is not colocalized
      with microcystic epithelium, mitotic activity, and inactive pGSK-3beta in
      collecting duct; a blocker of COX-2 does not prevent cell proliferation, cyst
      formation, or GSK-3beta inactivation. It is concluded that COX-2 activity is not
      the primary cause for microcysts and polyuria in a NaCl-substituted rat model of
      lithium nephropathy. COX-1 is a relevant candidate to affect the injured
      epithelium. 

PMID- 24744882
TI  - The effect of high [K(+)]o on spontaneous Ca(2+) waves in freshly isolated
      interstitial cells of Cajal from the rabbit urethra.
AB  - Interstitial cells of Cajal (ICC) act as putative pacemaker cells in the rabbit
      urethra. Pacemaker activity in ICC results from spontaneous global Ca(2+) waves
      that can be increased in frequency by raising external [K(+)]. The purpose of
      this study was to elucidate the mechanism of this response. Intracellular
      [Ca(2+)] was measured in fluo-4-loaded smooth muscle cells (SMCs) and ICC using a
      Nipkow spinning disk confocal microscope. Increasing [K(+)]o to 60 mmol/L caused
      an increase in [Ca(2+)]i accompanied by contraction in SMCs. Raising [K(+)]o did
      not cause contraction in ICC, but the frequency of firing of spontaneous calcium
      waves increased. Reducing [Ca(2+)]o to 0 mmol/L abolished the response in both
      cell types. Nifedipine of 1 MUmol/L blocked the response of SMC to high [K(+)]o,
      but did not affect the increase in firing in ICC. This latter effect was blocked
      by 30 MUmol/L NiCl2 but not by the T-type Ca(2+) channel blocker mibefradil (300
      nmol/L). However, inhibition of Ca(2+) influx via reverse-mode sodium/calcium
      exchange (NCX) using either 1 MUmol/L SEA0400 or 5 MUmol/L KB-R7943 did block the
      effect of high [K(+)]o on ICC. These data suggest that high K(+) solution
      increases the frequency of calcium waves in ICC by increasing Ca(2+) influx
      through reverse-mode NCX. 

PMID- 24744883
TI  - Diet-induced obesity alters skeletal muscle fiber types of male but not female
      mice.
AB  - Skeletal muscles are highly plastic tissues capable dramatic remodeling in
      response to use, disuse, disease, and other factors. Growing evidence suggests
      that adipose tissues exert significant effects on the basic fiber-type
      composition of skeletal muscles. In the current study, we investigated the long
      term effects of a high-fat diet and subsequent obesity on the muscle fiber types
      in C57 BLK/6J mice. Litters of mice were randomly assigned to either a high-fat
      diet or a control group at the time of weaning, and were maintained on this diet
      for approximately 1 year. Single fibers were harvested from the soleus and
      plantaris muscles, and fiber types were determined using SDS-PAGE. The high-fat
      diet mice were significantly heavier than the control mice (39.17 +/- 2.7 g vs.
      56.87 +/- 3.4 g; P < 0.0003), but muscle masses were not different. In male mice,
      the high-fat diet was associated with a significantly lower proportion of slow,
      type I fibers in the soleus muscle (40.4 +/- 3.5% vs. 29.33 +/- 2.6%; P <
      0.0165). Moreover, the proportion of type I fibers in the soleus of male mice was
      inversely proportional to the relative fatness of the male mice (P < 0.003; r (2)
      = 0.65), but no association was observed in female mice. In male mice, the
      decline in type I fibers was correlated with an increase in type I/IIA hybrid
      fibers, suggesting that the type I fibers were transformed primarily into these
      hybrids. The reported trends indicate that type I fibers are most susceptible to
      the effects of obesity, and that these fiber-type changes can be sex specific. 

PMID- 24744884
TI  - Poststimulation inhibition of the micturition reflex induced by tibial nerve
      stimulation in rats.
AB  - The purpose of this study was to determine the effect of tibial nerve stimulation
      (TNS) on the micturition reflex. Experiments were conducted in 24 rats under
      urethane anesthesia. A catheter was inserted into the bladder via the bladder
      dome for saline infusion. A cuff electrode was placed around right tibial nerve
      for stimulation. TNS (5 Hz, 0.2 msec pulse width) at 2-4 times the threshold (T)
      intensity for inducing a toe movement was applied either during slow (0.08
      mL/min) infusion of the bladder or for 30 min with an empty bladder. TNS had no
      effect on the micturition reflex when it was applied during slow bladder
      infusion. However, the 30-min TNS applied with an empty bladder induced
      poststimulation inhibition and significantly (P < 0.05) increased the bladder
      capacity to about 140% of prestimulation level in a 50-min period following the
      termination of stimulation. The bladder compliance was also significantly (P <
      0.05) increased after the 30-min TNS. These results suggest that different
      mechanisms might exist in acute- and post-TNS inhibition of micturition reflex.
      The animal model developed in this study will be very useful for further
      investigations of the neurotransmitter mechanisms underlying tibial
      neuromodulation of bladder function. 

PMID- 24744885
TI  - Individual synaptic vesicles from the electroplaque of Torpedo californica, a
      classic cholinergic synapse, also contain transporters for glutamate and ATP.
AB  - The type of neurotransmitter secreted by a neuron is a product of the vesicular
      transporters present on its synaptic vesicle membranes and the available
      transmitters in the local cytosolic environment where the synaptic vesicles
      reside. Synaptic vesicles isolated from electroplaques of the marine ray, Torpedo
      californica, have served as model vesicles for cholinergic neurotransmission.
      Many lines of evidence support the idea that in addition to acetylcholine,
      additional neurotransmitters and/or neuromodulators are also released from
      cholinergic synapses. We identified the types of vesicular neurotransmitter
      transporters present at the electroplaque using immunoblot and immunofluoresence
      techniques with antibodies against the vesicle acetylcholine transporter (VAChT),
      the vesicular glutamate transporters (VGLUT1, 2, and 3), and the vesicular
      nucleotide transporter (VNUT). We found that VAChT, VNUT, VGLUT 1 and 2, but not
      3 were present by immunoblot, and confirmed that the antibodies were specific to
      proteins of the axons and terminals of the electroplaque. We used a single
      vesicle imaging technique to determine whether these neurotransmitter
      transporters were present on the same or different populations of synaptic
      vesicles. We found that greater than 85% of vesicles that labeled for VAChT
      colabeled with VGLUT1 or VGLUT2, and approximately 70% colabeled with VNUT. Based
      upon confidence intervals, at least 52% of cholinergic vesicles isolated are
      likely to contain all four transporters. The presence of multiple types of
      neurotransmitter transporters - and potentially neurotransmitters - in individual
      synaptic vesicles raises fundamental questions about the role of cotransmitter
      release and neurotransmitter synergy at cholinergic synapses. 

PMID- 24744886
TI  - ATP metabolism in skeletal muscle arterioles.
AB  - The purpose of this study was to investigate the metabolism of Adenosine
      triphosphate (ATP) in skeletal muscle resistance arterioles and to determine
      whether this metabolism is altered during the rapid growth phase of the rat. We
      attempted to quantify ATP metabolism in gastrocnemius first-order arterioles from
      8-, 10-, and 12-week-old rats. We measured ATP metabolism using an ATPase/GTPase
      assay with whole vessel segments as well as using a real-time adenosine biosensor
      following electric field stimulation. Our first method of measuring ATP
      metabolism allowed us to measure the amount of free phosphate produced with ATP
      as a substrate. When ecto-nucleotidase activity was inhibited by ARL67156,
      pyridoxal phosphate-6-azophenly-2', 4'-disulfonic acid (PPADS), or suramin prior
      to adding ATP, we found that the rate of phosphate production was significantly
      reduced by 27%, 21%, and 22%, respectively (P < 0.05). Our second method of
      measuring ATP metabolism allowed us to measure the amount of adenosine produced
      following electric field stimulation of the arteriole with and without
      nucleotidase inhibitors. Surprisingly, we found that adenosine overflow was not
      attenuated by nucleotidase inhibitors. We concluded that ecto
      phosphodieterase/phyrophophatase (E-NPP), ecto-diadenosine polyphosphatase
      (ApnA), NTPDase1 and 2, and E5NT may be present on the gastrocnemius 1A arteriole
      and do play a role in ATP metabolism. Between the ages of 8 weeks and 12 weeks,
      however, overall ATP metabolism may not change. 

PMID- 24744887
TI  - Impaired ability to modulate glomerular filtration rate in aged female sheep
      following fetal uninephrectomy.
AB  - Fetal uninephrectomy (uni-x) results in hypertension at a later age in female
      than male sheep. We hypothesized that dysregulation of tubular sodium handling
      contributes to the reduced ability to regulate extracellular fluid (ECF)
      homeostasis in older females born with a congenital nephron deficit. Following
      renal excretory balance studies, the response to inhibition of the Na(+)K(+)2Cl(
      ) cotransporter with furosemide (0.5 mg/kg bolus + 1 mg/kg per hour, i.v) or
      vehicle treatment was examined in conscious 5-year-old female uni-x (n = 7) and
      sham (n = 7) sheep. Balance studies in meal-fed sheep demonstrated that while
      average 24 h sodium excretion over 6 days was not different between the groups,
      the daily variation in sodium excretion was significantly greater in uni-x
      compared to sham sheep (31 +/- 4% vs. 12 +/- 2%; P < 0.001). Basal plasma renin
      activity (PRA) and renal cortical cyclooxygenase-2 (COX-2) gene expression were
      lower in uni-x sheep (both, P < 0.01). The increases in glomerular filtration
      rate (GFR) and renal blood flow observed in sham sheep in response to furosemide
      were significantly attenuated in uni-x sheep (both P GROUP*TREAT < 0.05).
      However, fractional sodium excretion increased by a greater extent in the uni-x
      (4.4 +/- 1.0%) as compared to the sham sheep (2.0 +/- 0.4%; P GROUP*TIME < 0.05)
      in response to furosemide. In conclusion, fetal uni-x was associated with altered
      renal sodium handling and hypertension in aged females. The impaired ability to
      modulate PRA and GFR in the adults with a congenital nephron deficit may reduce
      the capacity of the kidney to respond to gains or losses in ECF to maintain a
      stable internal environment. 

PMID- 24744890
TI  - From morphological heterogeneity at alveolar level to the overall mechanical lung
      behavior: an in vivo microscopic imaging study.
AB  - In six male anesthetized, tracheotomized, and mechanically ventilated rabbits, we
      imaged subpleural alveoli under microscopic view (60*) through a "pleural window"
      obtained by stripping the endothoracic fascia and leaving the parietal pleura
      intact. Three different imaging scale levels were identified for the analysis on
      increasing stepwise local distending pressure (P ld) up to 16.5 cmH2O: alveoli,
      alveolar cluster, and whole image field. Alveolar profiles were manually traced,
      clusters of alveoli of similar size were identified through a contiguity
      constrained hierarchical agglomerative clustering analysis and alveolar surface
      density (ASD) was estimated as the percentage of air on the whole image field.
      Alveolar area distributions were remarkably right-skewed and showed an increase
      in median value with a large topology-independent heterogeneity on increasing P
      ld. Modeling of alveolar area distributions on increasing P ld led to hypothesize
      that absolute alveolar compliance (change in surface area over change in P ld)
      increases fairly linearly with increasing initial alveolar size, the corollary of
      this assumption being a constant specific compliance. Clusters were reciprocally
      interweaved due to their highly variable complex shapes. ASD was found to
      increase with a small coefficient of variation (CV <25%) with increasing P ld.
      The CV of lung volume at each transpulmonary pressure was further decreased
      (about 6%). The results of the study suggest that the considerable heterogeneity
      of alveolar size and of the corresponding alveolar mechanical behavior are
      homogenously distributed, resulting in a substantially homogenous mechanical
      behavior of lung units and whole organ. 

PMID- 24744891
TI  - Airway obstruction, dynamic hyperinflation, and breathing pattern during
      incremental exercise in COPD patients.
AB  - Ventilatory capacity is reduced in chronic obstructive pulmonary disease (COPD)
      patients. Tidal volume (V T) is lower and breathing frequency higher at a given
      ventilation (V E) compared to healthy subjects. We examined whether airflow
      limitation and dynamic hyperinflation in COPD patients were related to breathing
      pattern. An incremental treadmill exercise test was performed in 63 COPD patients
      (35 men), aged 65 years (48-79 years) with a mean forced expiratory volume in 1
      sec (FEV1) of 48% of predicted (SD = 15%). Data were averaged over 20-sec
      intervals. The relationship between V E and V T was described by the quadratic
      equation V T = a + bV E + cV E (2) for each subject. The relationships between
      the curve parameters b and c, and spirometric variables and dynamic
      hyperinflation measured as the difference in inspiratory capacity from start to
      end of exercise, were analyzed by multivariate linear regression. The
      relationship between V E and V T could be described by a quadratic model in 59
      patients with median R (2) of 0.90 (0.40-0.98). The linear coefficient (b) was
      negatively (P = 0.001) and the quadratic coefficient (c) positively (P < 0.001)
      related to FEV1. Forced vital capacity, gender, height, weight, age, inspiratory
      reserve volume, and dynamic hyperinflation were not associated with the curve
      parameters after adjusting for FEV1. We concluded that a quadratic model could
      satisfactorily describe the relationship between V E and V T in most COPD
      patients. The curve parameters were related to FEV1. With a lower FEV1, maximal V
      T was lower and achieved at a lower V E. Dynamic hyperinflation was not related
      to breathing pattern when adjusting for FEV1. 

PMID- 24744892
TI  - Catalyzing role of erythropoietin on the nitric oxide central pathway during the
      ventilatory responses to hypoxia.
AB  - The N-Methyl-d-Aspartate (NMDA) receptors - neuronal nitric oxide synthase (nNOS)
      pathway is involved in the ventilatory response to hypoxia. The objective was to
      assess the possible effect of erythropoietin deficiency and chronic exposure to
      hypoxia on this pathway during ventilatory response to acute hypoxia. Wild-type
      (WT) and erythropoietin-deficient (Epo-TAg(h)) male mice were exposed (14 days)
      either to hypobaric hypoxia (Pb = 435 mmHg) or to normoxia. The ventilation was
      measured at 21% or 8% O2 after injection of vehicle (NaCl), nNOS inhibitor (SMTC)
      or NMDA receptor antagonist (MK-801). Nitric oxide production and the expression
      of NMDA receptor and nNOS were assessed by real-time RT-PCR and Western blot
      analyses in the medulla. At rest, Epo-TAg(h) mice displayed normal ventilatory
      parameters at 21% O2 but did not respond to acute hypoxia despite a larger
      expression of NMDA receptors and nNOS in the medulla. Ventilatory acclimatization
      to hypoxia was observed in WT but was absent in Epo-TAg(h) mice. nNOS inhibition
      blunted the hypoxic ventilatory acclimatization of WT mice without any effect in
      Epo-TAg(h) mice. Acute hypoxic ventilatory response (HVR) was increased after
      chronic hypoxia in WT but remained unchanged in Epo-TAg(h) mice. Ventilatory
      response to acute hypoxia was modified by MK-801 injection in WT and Epo-TAg(h)
      mice. The results confirm that adequate erythropoietin level is necessary to
      obtain an appropriate HVR and a significant ventilatory acclimatization to
      hypoxia. Furthermore, erythropoietin plays a potential catalyzing role in the
      NMDA-NO central pathway during the ventilatory response and acclimatization to
      hypoxia. 

PMID- 24744893
TI  - MMP-1 and MMP-9 regulate epidermal growth factor-dependent collagen loss in human
      carotid plaque smooth muscle cells.
AB  - Mechanisms underlying the rupture of atherosclerotic plaque, a crucial factor in
      the development of myocardial infarction and stroke, are not well defined. Here,
      we examined the role of epidermal growth factor (EGF)-mediated matrix
      metalloproteinases (MMP) on the stability of interstitial collagens in vascular
      smooth muscle cells (VSMCs) isolated from carotid endarterectomy tissues of
      symptomatic and asymptomatic patients with carotid stenosis. VSMCs isolated from
      the carotid plaques of both asymptomatic and symptomatic patients were treated
      with EGF. The MMP-9 activity was quantified by gelatin zymography and the
      analysis of mRNA transcripts and protein for MMP-9, MMP-1, EGFR and collagen
      types I, Col I(alpha1) and collagen type III, Col III(alpha1) were analyzed by
      qPCR and immunofluorescence, respectively. The effect of EGF treatment to
      increase MMP-9 activity and mRNA transcripts for MMP-9, MMP-1, and EGFR and to
      decrease mRNA transcripts for Col I(alpha1) and Col III(alpha1) was threefold to
      fourfold greater in VSMCs isolated from the carotid plaques of symptomatic than
      asymptomatic patients. Inhibitors of EGFR (AG1478) and a small molecule inhibitor
      of MMP-9 decreased the MMP9 expression and upregulated Col I(alpha1) and Col
      III(alpha1) in EGF-treated VSMCs of both groups. Additionally, the magnitude in
      decreased MMP-9 mRNA and increased Col I(alpha1) and Col III(alpha1) due to
      knockdown of MMP-9 gene with siRNA in EGF-treated VSMCs was significantly greater
      in the symptomatic group than the asymptomatic group. Thus, a selective blockade
      of both EGFR and MMP-9 may be a novel strategy and a promising target for
      stabilizing vulnerable plaques in patients with carotid stenosis. 

PMID- 24744894
TI  - Differential regulation of adipose tissue and vascular inflammatory gene
      expression by chronic systemic inhibition of NOS in lean and obese rats.
AB  - We tested the hypothesis that a decrease in bioavailability of nitric oxide (NO)
      would result in increased adipose tissue (AT) inflammation. In particular, we
      utilized the obese Otsuka Long Evans Tokushima Fatty rat model (n = 20) and lean
      Long Evans Tokushima Otsuka counterparts (n = 20) to determine the extent to
      which chronic inhibition of NO synthase (NOS) with N (omega) -nitro-l-arginine
      methyl ester (L-NAME) treatment (for 4 weeks) upregulates expression of
      inflammatory genes and markers of immune cell infiltration in retroperitoneal
      white AT, subscapular brown AT, periaortic AT as well as in its contiguous aorta
      free of perivascular AT. As expected, relative to lean rats (% body fat = 13.5 +/
      0.7), obese rats (% body fat = 27.2 +/- 0.8) were hyperlipidemic (total
      cholesterol 77.0 +/- 2.1 vs. 101.0 +/- 3.3 mg/dL), hyperleptinemic (5.3 +/- 0.9
      vs. 191.9 +/- 59.9 pg/mL), and insulin-resistant (higher HOMA IR index [3.9 +/-
      0.8 vs. 25.2 +/- 4.1]). Obese rats also exhibited increased expression of
      proinflammatory genes in perivascular, visceral, and brown ATs. L-NAME treatment
      produced a small but statistically significant decrease in percent body fat (24.6
      +/- 0.9 vs. 27.2 +/- 0.8%) and HOMA IR index (16.9 +/- 2.3 vs. 25.2 +/- 4.1) in
      obese rats. Further, contrary to our hypothesis, we found that expression of
      inflammatory genes in all AT depots examined were generally unaltered with L-NAME
      treatment in both lean and obese rats. This was in contrast with the observation
      that L-NAME produced a significant upregulation of inflammatory and
      proatherogenic genes in the aorta. Collectively, these findings suggest that
      chronic NOS inhibition alters transcriptional regulation of proinflammatory genes
      to a greater extent in the aortic wall compared to its adjacent perivascular AT,
      or visceral white and subscapular brown AT depots. 

PMID- 24744895
TI  - Osmoreceptors do not exhibit a sex-dependent modulation of forearm skin blood
      flow and sweating.
AB  - Studies show that increases in plasma osmolality result in a delayed onset
      threshold of thermoeffector responses. However, it remains unclear if there are
      sex-related differences in the osmotically induced changes in both sweating and
      cutaneous vascular conductance (CVC). Nine young men and nine young women were
      passively heated (water-perfused suit) to 1.5 degrees C above baseline esophageal
      temperature while in an isosmotic (0.9% NaCl saline infusion) (ISO) and
      hyperosmotic (3% NaCl saline infusion) (HYP) state. Forearm sweat rate
      (ventilated capsule), skin blood flow (laser-Doppler), esophageal temperature and
      skin temperature were continuously recorded. Sweat gland output (SGO) on the
      forearm was calculated from the number of heat activated sweat glands (modified
      iodine-paper technique) at the end of heating. The onset threshold and
      thermosensitivity of sweating and CVC were determined using the linear portion of
      each response plotted against mean body temperature and analyzed using segmented
      regression analysis. We show that the osmotically induced delay in the onset
      threshold of sweating and CVC is similar between males and females. Although the
      thermosensitivity of CVC was similar between sexes (P = 0.601), the
      thermosensitivity of sweating was consistently lower in females compared to males
      (P = 0.018). The lower thermosensitivity in sudomotor response of females was
      accompanied by a lower SGO (P = 0.003), albeit similar sweat gland activation to
      males (P = 0.644). We conclude that sex-related differences in thermoeffector
      activity are independent of osmoreceptor activation. Therefore, osmoreceptors do
      not exhibit sex-related differences in the modulation of CVC and sweating
      responses during heat stress. 

PMID- 24744896
TI  - Possible contribution of pannexin-1 to ATP release in human upper airway
      epithelia.
AB  - Pannexins are a family of transmembrane nonselective channel proteins that
      participate in the release of ATP into extracellular space. Previous studies have
      suggested that pannexin-1 (Panx1) may constitute a local autocrine/paracrine
      system via transmitter ATP in association with the purinergic P2X7 receptor. In
      this study, we investigate the expressions of Panx1 and P2X7 in human nasal
      mucosa, together with hypotonic stress-induced ATP release from this tissue.
      Twenty men and one woman ranging in age from 10 to 82 years with an average age
      of 44.2 +/- 4.4 years participated in the study. Inferior turbinates were
      collected from patients with chronic hypertrophic rhinitis during endoscopic
      endonasal surgery. The expressions of Panx1 and P2X7 were examined by
      fluorescence immunohistochemistry and quantitative reverse transcription
      polymerase chain reaction (qRT-PCR). We also examined hypotonic stress-induced
      ATP release from the turbinate mucosa and the effects of channel blockers in an
      ex vivo experiment. Substantial expressions of both proteins were observed in
      human nasal mucosa. The immunoreactivity for Panx1 was stronger than that for
      P2X7. The presence of the transcripts of Panx1 and P2X7 was also shown by qRT
      PCR. Ten and 100 MUmol/L carbenoxolone (a Panx1 channel blocker) significantly
      inhibited the ATP release from the nasal mucosa, but flufenamic acid (a connexin
      channel blocker) and gadolinium (a stretch-activated channel blocker) did not.
      These results indicate the coexistence of Panx1 and P2X7 in, and Panx1-dependent
      ATP release from, the human nasal mucosa, suggesting the possible participation
      of these molecules in the physiological functions of the upper airway. 

PMID- 24744897
TI  - Decrease in IL-10 and increase in TNF-alpha levels in renal tissues during
      systemic inhibition of nitric oxide in anesthetized mice.
AB  - Earlier, we demonstrated that the inhibition of nitric oxide synthase (NOS) by
      nitro-l-arginine methyl ester (l-NAME) infusion increases the endogenous
      production of proinflammatory cytokine, tumor necrosis factor (TNF-alpha). In the
      present study, we examined the hypothesis that inhibition of nitric oxide (NO)
      production leads to the suppression of interleukin (IL)-10 (anti-inflammatory
      cytokine) generation which facilitates the enhancement of TNF-alpha production
      endogenously. Using appropriate enzyme-linked immunosorbent assay kits and
      immunohistochemical staining, the levels of IL-10 and TNF-alpha in plasma (P) and
      in renal tissues (R) were measured in anesthetized mice (C57BL/6; ~10 weeks age;
      n = 6/group) infused with or without l-NAME (200 MUg/min/kg; i.v. for 2 h).
      Compared to vehicle-treated control mice, l-NAME-treated mice had a lower level
      of IL-10 (P, 0.3 +/- 0.1 vs. 2.6 +/- 0.6 ng/mL; R, 0.5 +/- 0.1 vs. 3 +/- 0.1
      ng/mg protein) and a higher level of TNF-alpha (P, 432 +/- 82 vs. undetected
      pg/mL; R, 58 +/- 7 vs. 6 +/- 5 pg/mg protein). IL-10 protein expression, present
      mostly in the distal nephron segments in control mice, was markedly downregulated
      in l-NAME-treated mice. Compared to control mice, TNF-alpha expression increased
      2.5-fold in renal cortical sections (mostly in the distal nephron segments) in l
      NAME-treated mice. Coinfusion of a NO donor, S-nitroso-N-acetyl-penicillamine
      (SNAP; 25 MUg/min/kg) with l-NAME in a separate group of mice prevented these
      changes in IL-10 and TNF-alpha induced by l-NAME. IL-10 infusion (0.075 ng/min/g)
      in l-NAME-treated mice markedly attenuated l-NAME-induced increments in TNF
      alpha. Thus, these results demonstrate that NOS inhibition decreases endogenous
      IL-10 generation and thus, minimizes its immune downregulating action on the TNF
      alpha production in the kidney. 

PMID- 24744898
TI  - By counteracting gravity, triceps surae sets both kinematics and kinetics of
      gait.
AB  - In the single-stance phase of gait, gravity acting on the center of mass (CoM)
      causes a disequilibrium torque, which generates propulsive force. Triceps surae
      activity resists gravity by restraining forward tibial rotation thereby tuning
      CoM momentum. We hypothesized that time and amplitude modulation of triceps surae
      activity determines the kinematics (step length and cadence) and kinetics of
      gait. Nineteen young subjects participated in two experiments. In the gait
      initiation (GI) protocol, subjects deliberately initiated walking at different
      velocities for the same step length. In the balance-recovery (BR) protocol,
      subjects executed steps of different length after being unexpectedly released
      from an inclined posture. Ground reaction force was recorded by a large force
      platform and electromyography of soleus, gastrocnemius medialis and lateralis,
      and tibialis anterior muscles was collected by wireless surface electrodes. In
      both protocols, the duration of triceps activity was highly correlated with
      single-stance duration (GI, R (2) = 0.68; BR, R (2) = 0.91). In turn, step length
      was highly correlated with single-stance duration (BR, R (2) = 0.70). Control of
      CoM momentum was obtained by decelerating the CoM fall via modulation of
      amplitude of triceps activity. By modulation of triceps activity, the central
      nervous system (CNS) varied the position of CoM with respect to the center of
      pressure (CoP). The CoM-CoP gap in the sagittal plane was determinant for setting
      the disequilibrium torque and thus walking velocity. Thus, by controlling the
      gap, CNS-modified walking velocity (GI, R (2) = 0.86; BR, R (2) = 0.92). This
      study is the first to highlight that by merely counteracting gravity, triceps
      activity sets the kinematics and kinetics of gait. It also provides evidence that
      the surge in triceps activity during fast walking is due to the increased
      requirement of braking the fall of CoM in late stance in order to perform a
      smoother step-to-step transition. 

PMID- 24744899
TI  - Adiponectin retards the progression of diabetic nephropathy in db/db mice by
      counteracting angiotensin II.
AB  - Adiponectin is a multifunctional adipokine with insulin-sensitizing, anti
      inflammatory, and vasoprotective properties. Epidemiology studies have, however,
      shown that high levels of serum adiponectin are associated with kidney disease
      progression. We, therefore, examined the effect of adiponectin administration on
      the progression of glomerulosclerosis in the obese diabetic (db/db) mouse, a
      model of type II diabetes. Recombinant human adiponectin was administered
      intraperitoneally at a dose of 30 or 150 MUg per day from weeks 18 to 20.
      Rosiglitazone administered by gavage at 20 mg/kg body weight (BW) daily served as
      a therapeutic control. Untreated uninephrectomized db/db mice developed
      progressive albuminuria and glomerular matrix expansion, associated with
      increased expression of transforming growth factor beta 1 (TGFbeta1), plasminogen
      activator inhibitor type 1 (PAI-1), collagen I (Col I), and fibronectin (FN).
      Treatment with adiponectin at either dose reduced the increases in albuminuria
      and markers of renal fibrosis seen in db/db mice, without affecting BW and blood
      glucose. Renal expressions of tumor necrosis factor-alpha (TNF-alpha) and
      monocyte-chemoattractant protein-1 (MCP-1) and urinary TNF-alpha levels, the
      markers of renal inflammation, were increased in diabetic mice, whereas
      adiponectin treatment significantly reduced the levels of these markers.
      Furthermore, adiponectin obliterated the stimulatory effects of angiotensin II
      (Ang II), but not the total effect of TGFbeta1, on the mRNA expression of PAI-1,
      Col I, and FN by cultured glomerular mesangial cells. These observations suggest
      that adiponectin treatment reduces glomerulosclerosis resulting from type II
      diabetes probably through its anti-inflammatory and angiotensin-antagonistic
      effects. Thus, adiponectin has therapeutic implications in the prevention of
      progression of diabetic nephropathy. 

PMID- 24744900
TI  - Parathyroid hormone secretion by multiple distinct cell populations, a time
      dynamic mathematical model.
AB  - The acute response of parathyroid hormone to perturbations in serum ionized
      calcium ([Ca(2+)]) is physiologically complex, and poorly understood. The
      literature provides numerous observations of quantitative and qualitative
      descriptions of parathyroid hormone (PTH) dynamics. We present a physiologically
      based mathematical model of PTH secretion constructed from mechanisms suggested
      in the literature, and validated against complex [Ca(2+)] clamping protocols from
      human data. The model is based on two assumptions. The first is that secretion is
      a fraction of cellular reserves, with the fraction being determined by the
      kinetics of [Ca(2+)] with its receptor. The second is that there are multiple
      distinct populations of parathyroid cells, with different secretory parameters.
      The steady state and transient PTH secretion responses of the model are in
      agreement with human experimental PTH responses to different hypocalcemia and
      hypercalcemia stimuli. This mathematical model suggests that a population of
      secreting cells is responsible for the PTH secretory dynamics observed
      experimentally. 

PMID- 24744901
TI  - Balance control and anti-gravity muscle activity during the experience of fear at
      heights.
AB  - Fear of heights occurs when a visual stimulus causes the apprehension of losing
      balance and falling. A moderate form of visual height intolerance (vHI) affects
      about one third of the general population and has relevant consequences for the
      quality of life. A quantitative evaluation of balance mechanisms in persons
      susceptible to vHI during height exposure is missing. VHI-related changes in
      postural control were assessed by center-of-pressure displacements and
      electromyographic recordings of selected leg, arm, and neck muscles in 16
      subjects with vHI while standing at heights on an emergency balcony versus
      standing in the laboratory at ground level. Characteristics of open- and closed
      loop postural control were analyzed. Body sway and muscle activity parameters
      were correlated with the subjective estimates of fear at heights. During height
      exposure, (1) open-loop control was disturbed by a higher diffusion activity (P <
      0.001) and (2) the sensory feedback threshold for closed-loop control was lowered
      (P < 0.010). Altered postural control was predominantly associated with increased
      co-contraction of leg muscles. Body sway and leg and neck muscle co-contraction
      correlated with the severity of subjective anxiety (P < 0.050). Alterations in
      postural control diminished if there were nearby stationary contrasts in the
      visual surrounding or if subjects stood with eyes closed. The performance of a
      cognitive dual task also improved impaired balance. Visual heights have two
      behavioral effects in vHI subjects: A change occurs in (1) open- and closed-loop
      postural control strategy and (2) co-contraction of anti-gravity leg and neck
      muscles, both of which depend on the severity of evoked fear at heights. 

PMID- 24744902
TI  - The cerebrovascular response to graded Valsalva maneuvers while standing.
AB  - The Valsalva maneuver (VM) produces large and abrupt increases in mean arterial
      pressure (MAP) at the onset of strain (Phase I), however, hypotension, sufficient
      to induce syncope, occurs upon VM release (phase III). We examined the effect of
      VM intensity and duration on middle cerebral artery blood velocity (MCAv)
      responses. Healthy men (n =10; mean +/- SD: 26 +/- 4 years) completed 30%, 60%,
      and 90% of their maximal VM mouth pressure, for 5 and 10 sec (order randomized)
      while standing. Beat-to-beat MCAv and MAP during phase I (peak), at nadir (phase
      III), and recovery are reported as the change from standing baseline. During
      phase I, MCAv rose 15 +/- 6 cm.s(-1) (P <0.001), which was not reliably different
      between intensities (P =0.11), despite graded increases in MAP (P <0.001; e.g.,
      +12 +/- 9 mmHg vs. +35 +/- 14 for 5 sec 30% and 90% VM, respectively). During
      Phase III, the MCAv response was duration- (P = 0.045) and intensity dependent (P
      < 0.001), with the largest decrease observed following the 90% VM (e.g., -19 +/-
      13 and -15 +/- 11 cm.s(-1) for 5 and 10 sec VM, respectively) with a concomitant
      decrease in MAP (P <0.001, -23 +/- 11 and -23 +/- 9 mmHg). This asymmetric
      response may be attributable to the differential modulators of MCAv throughout
      the VM. The mechanical effects of the elevated intrathoracic pressure during
      phase I may restrain increases in cerebral perfusion via related increases in
      intracranial pressure; however, during phase III the decrease in MCAv arises from
      an abrupt hypotension, the extent of which is dependent upon both the duration
      and intensity of the VM. 

PMID- 24744903
TI  - Experimental peripheral arterial disease: new insights into muscle glucose
      uptake, macrophage, and T-cell polarization during early and late stages.
AB  - Peripheral arterial disease (PAD) is a common disease with increasing prevalence,
      presenting with impaired walking ability affecting patient's quality of life. PAD
      epidemiology is known, however, mechanisms underlying functional muscle
      impairment remain unclear. Using a mouse PAD model, aim of this study was to
      assess muscle adaptive responses during early (1 week) and late (5 weeks) disease
      stages. Unilateral hindlimb ischemia was induced in ApoE(-/-) mice by iliac
      artery ligation. Ischemic limb perfusion and oxygenation (Laser Doppler imaging,
      transcutaneous oxygen pressure assessments) significantly decreased during early
      and late stage compared to pre-ischemia, however, values were significantly
      higher during late versus early phase. Number of arterioles and arteriogenesis
      linked gene expression increased at later stage. Walking ability, evaluated by
      forced and voluntary walking tests, remained significantly decreased both at
      early and late phase without any significant improvement. Muscle glucose uptake
      ([18F]fluorodeoxyglucose positron emission tomography) significantly increased
      during early ischemia decreasing at later stage. Gene expression analysis showed
      significant shift in muscle M1/M2 macrophages and Th1/Th2 T cells balance toward
      pro-inflammatory phenotype during early ischemia; later, inflammatory state
      returned to neutrality. Muscular M1/M2 shift inhibition by a statin prevented
      impaired walking ability in early ischemia. High-energy phosphate metabolism
      remained unchanged (31-Phosphorus magnetic resonance spectroscopy). Results show
      that rapid transient muscular inflammation contributes to impaired walking
      capacity while increased glucose uptake may be a compensatory mechanisms
      preserving immediate limb viability during early ischemia in a mouse PAD model.
      With time, increased ischemic limb perfusion and oxygenation assure muscle
      viability although not sufficiently to improve walking impairment. Subsequent
      decreased muscle glucose uptake may partly contribute to chronic walking
      impairment. Early inflammation inhibition and/or late muscle glucose impairment
      prevention are promising strategies for PAD management. 

PMID- 24744904
TI  - GDNF content and NMJ morphology are altered in recruited muscles following high
      speed and resistance wheel training.
AB  - Glial cell line-derived neurotrophic factor (GDNF) may play a role in delaying
      the onset of aging and help compress morbidity by preventing motor unit
      degeneration. Exercise has been shown to alter GDNF expression differently in
      slow- and fast-twitch myofibers. The aim was to examine the effects of different
      intensities (10, 20, ~30, and ~40 m.min(-1)) of wheel running on GDNF expression
      and neuromuscular junction (NMJ) plasticity in slow- and fast-twitch myofibers.
      Male Sprague-Dawley Rats (4 weeks old) were divided into two sedentary control
      groups (CON4 week, n = 5 and CON6 week, n = 5), two involuntary running groups,
      one at a low velocity; 10 m/min (INVOL-low, n = 5), and one at a higher velocity;
      20 m/min (INVOL-high, n = 5), and two voluntary running groups with resistance
      (VOL-R, n = 5, 120 g), and without resistance (VOL-NR, n = 5, 4.5 g). GDNF
      protein content, determined by enzyme-linked immunosorbent assay (ELISA),
      increased significantly in the recruited muscles. Plantaris (PLA) GDNF protein
      content increased 174% (P <0.05) and 161% (P <0.05) and end plate-stained area
      increased 123% (P <0.05) and 72% (P <0.05) following VOL-R, and VOL-NR training,
      respectively, when compared to age-matched controls. A relationship exists
      between GDNF protein content and end plate area (r = 0.880, P < 0.01, n = 15).
      VOL-R training also resulted in more dispersed synapses in the PLA muscle when
      compared to age-matched controls (P <0.05). Higher intensity exercise (>30 m/min)
      can increase GDNF protein content in fast-twitch myofibers as well as induce
      changes in the NMJ morphology. These findings help to inform exercise
      prescription to preserve the integrity of the neuromuscular system through aging
      and disease. 

PMID- 24744905
TI  - Radius exponent in elastic and rigid arterial models optimized by the least
      energy principle.
AB  - It was analyzed in normal physiological arteries whether the least energy
      principle would suffice to account for the radius exponent x. The mammalian
      arterial system was modeled as two types, the elastic or the rigid, to which
      Bernoulli's and Hagen-Poiseuille's equations were applied, respectively. We
      minimized the total energy function E, which was defined as the sum of kinetic,
      pressure, metabolic and thermal energies, and loss of each per unit time in a
      single artery transporting viscous incompressible blood. Assuming a scaling
      exponent alpha between the vessel radius (r) and length (l) to be 1.0, x resulted
      in 2.33 in the elastic model. The rigid model provided a continuously changing x
      from 2.33 to 3.0, which corresponded to Uylings' and Murray's theories,
      respectively, through a function combining Reynolds number with a proportional
      coefficient of the l - r relationship. These results were expanded to an
      asymmetric arterial fractal tree with the blood flow preservation rule. While x
      in the optimal elastic model accounted for around 2.3 in proximal systemic (r >1
      mm) and whole pulmonary arteries (r >=0.004 mm), optimal x in the rigid model
      explained 2.7 in elastic-muscular (0.1 < r <=1 mm) and 3.0 in peripheral
      resistive systemic arteries (0.004 <= r <=0.1 mm), in agreement with data
      obtained from angiographic, cast-morphometric, and in vivo experimental studies
      in the literature. The least energy principle on the total energy basis provides
      an alternate concept of optimality relating to mammalian arterial fractal
      dimensions under alpha = 1.0. 

PMID- 24744906
TI  - Overexpression of myocardin induces partial transdifferentiation of human-induced
      pluripotent stem cell-derived mesenchymal stem cells into cardiomyocytes.
AB  - Mesenchymal stem cells (MSCs) derived from human-induced pluripotent stem cells
      (iPSCs) show superior proliferative capacity and therapeutic potential than those
      derived from bone marrow (BM). Ectopic expression of myocardin further improved
      the therapeutic potential of BM-MSCs in a mouse model of myocardial infarction.
      The aim was of this study was to assess whether forced myocardin expression in
      iPSC-MSCs could further enhance their transdifferentiation to cardiomyocytes and
      improve their electrophysiological properties for cardiac regeneration. Myocardin
      was overexpressed in iPSC-MSCs using viral vectors (adenovirus or lentivirus).
      The expression of smooth muscle cell and cardiomyocyte markers, and ion channel
      genes was examined by reverse transcription-polymerase chain reaction (RT-PCR),
      immunofluorescence staining and patch clamp. The conduction velocity of the
      neonatal rat ventricular cardiomyocytes cocultured with iPSC-MSC monolayer was
      measured by multielectrode arrays recording plate. Myocardin induced the
      expression of alpha-MHC, GATA4, alpha-actinin, cardiac MHC, MYH11, calponin, and
      SM alpha-actin, but not cTnT, beta-MHC, and MLC2v in iPSC-MSCs. Overexpression of
      myocardin in iPSC-MSC enhanced the expression of SCN9A and CACNA1C, but reduced
      that of KCa3.1 and Kir2.2 in iPSC-MSCs. Moreover, BKCa, IKir, ICl, Ito and
      INa.TTX were detected in iPSC-MSC with myocardin overexpression; while only BKCa,
      IKir, ICl, IKDR, and IKCa were noted in iPSC-MSC transfected with green
      florescence protein. Furthermore, the conduction velocity of iPSC-MSC was
      significantly increased after myocardin overexpression. Overexpression of
      myocardin in iPSC-MSCs resulted in partial transdifferentiation into
      cardiomyocytes phenotype and improved the electrical conduction during
      integration with mature cardiomyocytes. 

PMID- 24744907
TI  - Diet-induced obesity in mice reduces placental efficiency and inhibits placental
      mTOR signaling.
AB  - As in humans, obesity during pregnancy in mice results in elevated maternal
      insulin levels and metabolic programming of offspring. mTOR signaling regulates
      amino acid transport and may function as a placental nutrient sensor. Because
      obesity is a condition with increased nutrient availability, we hypothesized that
      diet-induced obesity activates placental mTOR signaling. To test this hypothesis,
      female C57BL/6J mice were fed an obesogenic diet or standard chow prior to and
      throughout pregnancy. Fetuses and placentas were collected at gestational day 18.
      Using Western blot analysis, placental mTOR activity was determined along with
      energy, inflammatory, and insulin signaling pathways (upstream modulators of
      mTOR). At gestational day 18, fetal and placental weights did not differ,
      however, in obese dams, the fetal/placental weight ratio was lower (P <0.01). In
      placentas from obese dams, mTOR signaling was inhibited, as determined by
      decreased Rheb and S6K1 expression, and lower rpS6 phosphorylation (P <0.05). In
      contrast, energy, inflammatory, and insulin signaling pathways were unaffected.
      Contrary to our hypothesis, diet-induced obesity in pregnant mice was associated
      with inhibition of placental mTOR signaling. However, this finding is consistent
      with the lower fetal/placental weight ratio, indicating reduced placental
      efficiency. 

PMID- 24744908
TI  - PAH clearance after renal ischemia and reperfusion is a function of impaired
      expression of basolateral Oat1 and Oat3.
AB  - Determination of renal plasma flow (RPF) by para-aminohippurate (PAH) clearance
      leads to gross underestimation of this respective parameter due to impaired renal
      extraction of PAH after renal ischemia and reperfusion injury. However, no
      mechanistic explanation for this phenomenon is available. Based on our own
      previous studies we hypothesized that this may be due to impairment of expression
      of the basolateral rate limiting organic anion transporters Oat1 and Oat3. Thus,
      we investigated this phenomenon in a rat model of renal ischemia and reperfusion
      by determining PAH clearance, PAH extraction, PAH net secretion, and the
      expression of rOat1 and rOat3. PAH extraction was seriously impaired after
      ischemia and reperfusion which led to a threefold underestimation of RPF when PAH
      extraction ratio was not considered. PAH extraction directly correlated with the
      expression of basolateral Oat1 and Oat3. Tubular PAH secretion directly
      correlated with PAH extraction. Consequently, our data offer an explanation for
      impaired renal PAH extraction by reduced expression of the rate limiting
      basolateral organic anion transporters Oat1 and Oat3. Moreover, we show that
      determination of PAH net secretion is suitable to correct PAH clearance for
      impaired extraction after ischemia and reperfusion in order to get valid results
      for RPF. 

PMID- 24744909
TI  - The neurogenic phase of angiotensin II-salt hypertension is prevented by chronic
      intracerebroventricular administration of benzamil.
AB  - Hypertension induced by chronic administration of angiotensin II (AngII) is
      exacerbated by high-salt intake. Previous studies have demonstrated that this
      salt-sensitive component is due to increased activity of the sympathetic nervous
      system, suggesting an interaction of plasma AngII with sodium-sensitive regions
      of the brain. This study tested the hypothesis that the salt-sensitive component
      of AngII-induced hypertension would be prevented by intracerebroventricular (ICV)
      administration of the sodium channel/transporter blocker benzamil. Male Sprague
      Dawley rats were instrumented to measure mean arterial pressure (MAP) by radio
      telemetry and for ICV administration of benzamil or vehicle and placed in
      metabolic cages for measurement of sodium and water intake and excretion. In rats
      consuming a high-salt diet (2.0% NaCl) and treated with ICV vehicle,
      administration of AngII (150 ng/kg/min, sc) for 13 days increased MAP by ~30
      mmHg. ICV administration of benzamil (16 nmol/day) had no effect during the first
      5 days of AngII, but returned MAP to control levels by Day 13. There were minimal
      or no differences between ICV vehicle or benzamil groups in regards to sodium and
      water balance. A lower dose of ICV benzamil administered ICV at 8 nmol/day had no
      effect on the MAP response to AngII in rats on a high-salt diet. Finally, in
      contrast to rats on a high-salt diet, AngII had negligible effects on MAP in rats
      consuming a low-salt diet (0.1% NaCl) and there were no differences in any
      variable between ICV benzamil (16 nmol/day) and ICV vehicle-treated groups. We
      conclude that the salt-sensitive component of AngII-induced hypertension is
      dependent on benzamil blockable sodium channels or transporters in the brain. 

PMID- 24744910
TI  - Changes in REDD1, REDD2, and atrogene mRNA expression are prevented in skeletal
      muscle fixed in a stretched position during hindlimb immobilization.
AB  - Immobilized skeletal muscle fixed in a shortened position displays disuse
      atrophy, whereas when fixed in a stretched position it does not (Goldspink, D. F.
      (1977) J Physiol 264, 267-282). Although significant advances have been made in
      our understanding of mechanisms involved in development of atrophy in muscle
      fixed in a shortened position, little is known about why mass is maintained when
      muscle is immobilized in a stretched position. In the present study, we
      hypothesized that skeletal muscle immobilized in a stretched position would be
      protected from gene expression changes known to be associated with disuse
      atrophy. To test the hypothesis, male Sprague-Dawley rats were anesthetized using
      isoflurane and subjected to unilateral hindlimb immobilization for 3 days with
      the soleus fixed in either a shortened or stretched position. All comparisons
      were made to the contralateral nonimmobilized muscle. Soleus immobilized in a
      shortened position exhibited disuse atrophy, attenuated rates of protein
      synthesis, attenuated mTORC1 signaling, and induced expression of genes for
      REDD1, REDD2, MAFbx, and MuRF1. In contrast, immobilization of the soleus in a
      stretched position prevented these changes as it exhibited no difference in
      muscle mass, rates of protein synthesis, mTORC1 signaling, or expression of genes
      encoding REDD1, MAFbx or MuRF1, with REDD2 expression being reduced compared to
      control. In conclusion, fixed muscle length plays a major role in immobilization
      induced skeletal muscle atrophy whereby placing muscle in a shortened position
      leads to induction of gene expression for REDD1, REDD2, and atrogenes. 

PMID- 24744911
TI  - Low force contractions induce fatigue consistent with muscle mRNA expression in
      people with spinal cord injury.
AB  - Spinal cord injury (SCI) is associated with muscle atrophy, transformation of
      muscle fibers to a fast fatigable phenotype, metabolic inflexibility (diabetes),
      and neurogenic osteoporosis. Electrical stimulation of paralyzed muscle may
      mitigate muscle metabolic abnormalities after SCI, but there is a risk for a
      fracture to the osteoporotic skeletal system. The goal of this study was to
      determine if low force stimulation (3 Hz) causes fatigue of chronically paralyzed
      muscle consistent with selected muscle gene expression profiles. We tested 29
      subjects, nine with a SCI and 20 without and SCI, during low force fatigue
      protocol. Three SCI and three non-SCI subjects were muscle biopsied for gene and
      protein expression analysis. The fatigue index (FI) was 0.21 +/- 0.27 and 0.91 +/
      0.01 for the SCI and non-SCI groups, respectively, supporting that the low force
      protocol physiologically fatigued the chronically paralyzed muscle. The post
      fatigue potentiation index (PI) for the SCI group was increased to 1.60 +/- 0.06
      (P <0.001), while the non-SCI group was 1.26 +/- 0.02 supporting that calcium
      handling was compromised with the low force stimulation. The mRNA expression from
      genes that regulate atrophy and fast properties (MSTN, ANKRD1, MYH8, and MYCBP2)
      was up regulated, while genes that regulate oxidative and slow muscle properties
      (MYL3, SDHB, PDK2, and RyR1) were repressed in the chronic SCI muscle. MSTN,
      ANKRD1, MYH8, MYCBP2 gene expression was also repressed 3 h after the low force
      stimulation protocol. Taken together, these findings support that a low force
      single twitch activation protocol induces paralyzed muscle fatigue and subsequent
      gene regulation. These findings suggest that training with a low force protocol
      may elicit skeletal muscle adaptations in people with SCI. 

PMID- 24744912
TI  - A mouse model of chronic idiopathic pulmonary fibrosis.
AB  - Chronic idiopathic pulmonary fibrosis (IPF) is a progressive, fatal, and
      untreatable disease with unclear etiology. There are few models of this chronic
      pathology, and although delivery of bleomycin to induce acute lung injury is the
      most common animal model of pulmonary fibrosis, there is considerable uncertainty
      about whether this acute injury resolves in those animals that survive. In this
      report, we have systematically followed groups of mice for up to 6 months
      following a single insult of bleomycin. We assessed changes in lung function and
      pathology over this time course, with measurements of the diffusion capacity for
      carbon monoxide, lung mechanics, quantitative stereology, and collagen. Our
      results show that, while there is some repair over this extended time course, the
      injury in the lung never fully resolves. This persistent degree of fibrosis may
      have similarities to many features of human IPF. Thus, these chronic fibrotic
      changes in mouse lungs could be a useful model to evaluate potential therapeutic
      interventions to accelerate repair and possible treat this debilitating disease. 

PMID- 24744914
TI  - Corrigendum.

PMID- 24744913
TI  - Liver but not adipose tissue is responsive to the pattern of enteral feeding.
AB  - Nutritional support is an important aspect of medical care, providing calories to
      patients with compromised nutrient intake. Metabolism has a diurnal pattern,
      responding to the light cycle and food intake, which in turn can drive changes in
      liver and adipose tissue metabolism. In this study, we assessed the response of
      liver and white adipose tissue (WAT) to different feeding patterns under
      nutritional support (total enteral nutrition or TEN). Mice received continuous
      isocaloric TEN for 10 days or equal calories of chow once a day (Ch). TEN was
      given either at a constant (CN, same infusion rate during 24 h) or variable rate
      (VN, 80% of calories fed at night, 20% at day). Hepatic lipogenesis and
      carbohydrate-responsive element-binding protein (ChREBP) expression increased in
      parallel with the diurnal feeding pattern. Relative to Ch, both patterns of
      enteral feeding increased adiposity. This increase was not associated with
      enhanced lipogenic gene expression in WAT; moreover, lipogenesis was unaffected
      by the feeding pattern. Surprisingly, leptin and adiponectin expression
      increased. Moreover, nutritional support markedly increased hepatic and adipose
      FGF21 expression in CN and VN, despite being considered a fasting hormone. In
      summary, liver but not WAT, respond to the pattern of feeding. While hepatic
      lipid metabolism adapts to the pattern of nutrient availability, WAT does not.
      Moreover, sustained delivery of nutrients in an isocaloric diet can cause
      adiposity without the proinflammatory state observed in hypercaloric feeding.
      Thus, the liver but not adipose tissue is responsive to the pattern of feeding
      behavior. 

PMID- 24744915
TI  - A novel method for the localization and management of traumatic cyclodialysis
      cleft.
AB  - Purpose. To propose a novel surgical method for the localization and management
      of traumatic cyclodialysis clefts. Methods. Five patients with traumatic
      cyclodialysis clefts who underwent the innovative surgery were retrospectively
      reviewed. The new method was introduced to repair a cyclodialysis cleft with two
      running sutures from the middle to each end of the cleft under the guidance of a
      probe. Preoperative and postoperative visual acuity (VA), intraocular pressure
      (IOP), slit lamp and gonioscopic results, ultrasound biomicroscopy (UBM), and
      optical coherence tomography (OCT) findings were recorded. Results. Cyclodialysis
      clefts were completely closed postoperatively in four patients (four eyes); this
      was confirmed by progressively improved VA, restoration into the normal range of
      the IOP, disappearance of suprachoroidal fluid, and reduced macular edema. Only
      one patient with multiple clefts had an incomplete reattachment. Conclusions.
      This clinical study offers a novel and efficient method to localize and repair
      the cyclodialysis clefts. 

PMID- 24744916
TI  - Effect of Chromium(VI) Toxicity on Enzymes of Nitrogen Metabolism in Clusterbean
      (Cyamopsis tetragonoloba L.).
AB  - Heavy metals are the intrinsic component of the environment with both essential
      and nonessential types. Their excessive levels pose a threat to plant growth and
      yield. Also, some heavy metals are toxic to plants even at very low
      concentrations. The present investigation (a pot experiment) was conducted to
      determine the affects of varying chromium(VI) levels (0.0, 0.5, 1.0, 2.0, and 4.0
      mg chromium(VI) kg(-1) soil in the form of potassium dichromate) on the key
      enzymes of nitrogen metabolism in clusterbean. Chromium treatment adversely
      affect nitrogenase, nitrate reductase, nitrite reductase, glutamine synthetase,
      and glutamate dehydrogenase in various plant organs at different growth stages as
      specific enzyme activity of these enzymes decreased with an increase in
      chromium(VI) levels from 0 to 2.0 mg chromium(VI) kg(-1) soil and 4.0 mg
      chromium(VI) kg(-1) soil was found to be lethal to clusterbean plants. In
      general, the enzyme activity increased with advancement of growth to reach
      maximum at flowering stage and thereafter decreased at grain filling stage. 

PMID- 24744917
TI  - Psychosocial Functioning in Depressive Patients: A Comparative Study between
      Major Depressive Disorder and Bipolar Affective Disorder.
AB  - Introduction. Major depressive disorder (MDD) and bipolar affective disorder
      (BAD) are among the leading causes of disability. These are often associated with
      widespread impairments in all domains of functioning including relational,
      occupational, and social. The main aim of the study was to examine and compare
      nature and extent of psychosocial impairment of patients with MDD and BAD during
      depressive phase. Methodology. 96 patients (48 in MDD group and 48 in BAD group)
      were included in the study. Patients were recruited in depressive phase (moderate
      to severe depression). Patients having age outside 18-45 years, psychotic
      symptoms, mental retardation, and current comorbid medical or axis-1 psychiatric
      disorder were excluded. Psychosocial functioning was assessed using Range of
      Impaired Functioning Tool (LIFE-RIFT). Results. Domains of work, interpersonal
      relationship, life satisfaction, and recreation were all affected in both groups,
      but the groups showed significant difference in global psychosocial functioning
      score only (P = 0.031) with BAD group showing more severe impairment. Conclusion.
      Bipolar depression causes higher global psychosocial impairment than unipolar
      depression. 

PMID- 24744918
TI  - An Overview of Depression among Transgender Women.
AB  - Rates of depression are higher in transgender women than in the general
      population, warranting an understanding of the variables related to depression in
      this group. Results of the literature review of depression in transgender women
      reveal several variables influencing depression, including social support,
      violence, sex work, and gender identity. The theoretical constructs of minority
      stress, coping, and identity control theory are explored in terms of how they may
      predict depression in transgender women. Depression and depressive symptoms have
      been used to predict high-risk sexual behaviors with mixed results. The
      implications of the findings on treating depression in transgender women include
      taking into account the stress of transition and the importance of supportive
      peers and family. Future studies should explore a model of depression and high
      risk behaviors in transgender women. 

PMID- 24744919
TI  - Protection of liver as a remote organ after renal ischemia-reperfusion injury by
      renal ischemic postconditioning.
AB  - This study was designed to investigate the protective effects of local renal
      ischemic postconditioning (POC) on liver damage after renal ischemia-reperfusion
      (IR) injury. Male rats were divided into three groups  (n = 8). They underwent a
      right nephrectomy before induction of 45 minutes of left kidney ischemia or sham
      operation. POC was performed by four cycles of 10 seconds of ischemia and 10
      seconds of reperfusion just at the beginning of 24 hours of reperfusion. Then
      blood and liver samples were collected to measure serum aspartate
      aminotransferase (AST), alanine aminotransferase (ALT), and liver oxidative
      stress parameters including superoxide dismutase (SOD) activity and
      malondialdehyde (MDA) level. Renal IR caused a significant increase in liver
      functional indices as demonstrated by increased serum AST and ALT compared to
      sham group. These parameters reduced significantly in POC group compared to IR
      group. Liver MDA levels increased and SOD activity decreased in IR group compared
      to sham group. Induction of POC reduced the elevated liver MDA levels and
      increased the reduced liver SOD activity. These results revealed that renal IR
      injury causes liver damage as a remote organ and POC protects liver from renal IR
      injury by a modification in the hepatic oxidative stress status. 

PMID- 24744920
TI  - Imhotep and the discovery of cerebrospinal fluid.
AB  - Herbowski (2013) suggested recently the Egyptian Imhotep from the 3rd dynasty in
      Egypt to be the discoverer of cerebrospinal fluid. There are, however, no sources
      within the first 2000 years after Imhotep suggesting him to be in any way
      connected with the field of medicine. Over the course of three millennia Imhotep
      evolves into the sage who besides architecture also masters the arts of medicine,
      magic, astronomy, and astrology, at the same time as him being transformed from
      man to demi-God, and finally to a God. The identification of Imhotep as a doctor
      has thus little to do with facts and it is unlikely that he had anything to do
      with the Edwin-Smith papyrus from a much later period where CSF is first
      mentioned. 

PMID- 24744921
TI  - Antibiotic conjugated fluorescent carbon dots as a theranostic agent for
      controlled drug release, bioimaging, and enhanced antimicrobial activity.
AB  - A novel report on microwave assisted synthesis of bright carbon dots (C-dots)
      using gum arabic (GA) and its use as molecular vehicle to ferry ciprofloxacin
      hydrochloride, a broad spectrum antibiotic, is reported in the present work.
      Density gradient centrifugation (DGC) was used to separate different types of C
      dots. After careful analysis of the fractions obtained after centrifugation,
      ciprofloxacin was attached to synthesize ciprofloxacin conjugated with C-dots
      (Cipro @ C-dots conjugate). Release of ciprofloxacin was found to be extremely
      regulated under physiological conditions. Cipro @ C-dots were found to be
      biocompatible on Vero cells as compared to free ciprofloxacin (1.2 mM) even at
      very high concentrations. Bare C-dots ( ~ 13 mg mL(-1)) were used for microbial
      imaging of the simplest eukaryotic model-Saccharomyces cerevisiae (yeast). Bright
      green fluorescent was obtained when live imaging was performed to view yeast
      cells under fluorescent microscope suggesting C-dots incorporation inside the
      cells. Cipro @ C-dots conjugate also showed enhanced antimicrobial activity
      against both model gram positive and gram negative microorganisms. Thus, the
      Cipro @ C-dots conjugate paves not only a way for bioimaging but also an
      efficient new nanocarrier for controlled drug release with high antimicrobial
      activity, thereby serving potential tool for theranostics. 

PMID- 24744922
TI  - Detection of Legionella spp. from Domestic Water in the Prefecture of Arta,
      Greece.
AB  - The aim of this research was the isolation of Legionella spp. from domestic water
      supply networks in the Prefecture of Arta. A total of 100 water samples, from 25
      houses, were collected. Half of the samples concerned the cold water and half the
      hot water supply. Purpose was to detect colonization of the water networks with
      Legionella spp. >500 cfu/L by using the method of filtration (ISO 11731). Out of
      100 samples, 6 samples from 3 houses were positive for Legionella spp. Legionella
      pneumophila serogroup 2-14 was isolated in 5 of 6 samples, whereas in the sixth
      sample Legionella anisa was identified. Only three of the samples had residual
      chloride over 0.2 mg/L, rate which is necessary for potable water, according to
      the Greek hygienic practice. Concerning the temperature of hot water, the mean
      temperature of the negative for Legionella samples was higher compared to the
      mean temperature of the positive for Legionella samples (49.9 degrees C versus
      45.5 degrees C). It is estimated that there is risk of infection through the use
      of showers. The low concentration of chloride and the temperature, which was
      found within the limits favorable to developing Legionella spp. (20-45 degrees
      C), provide fertile ground for proliferation of the bacteria. 

PMID- 24744923
TI  - Thermostability of Probiotics and Their alpha -Galactosidases and the Potential
      for Bean Products.
AB  - Soybeans and other pulses contain oligosaccharides which may cause intestinal
      disturbances such as flatulence. This study was undertaken to investigate alpha 
      galactosidase-producing probiotics added to frozen foods which can survive
      warming treatments used in thawing and consumption of the pulses. The maximum
      alpha -galactosidase activity (1.26 U/mg protein) was found in Bifidobacterium
      breve S46. Lactobacillus casei had the highest alpha -galactosidase
      thermostability among the various strains, with D values of 35, 29, and 9.3
      minutes at 50 degrees C, 55 degrees C, and 60 degrees C, respectively. The enzyme
      activity was less affected than viable cells by heating. However, the D values of
      two bacterial enzymes were lower than those of three commercial alpha 
      galactosidase-containing products. Freshly grown cells and their enzymes were
      more stable than the rehydrated cultures and their enzymes. Practical
      Application. Enzymes and cultures can be added to foods in order to enhance the
      digestibility of carbohydrates in the gastrointestinal tract. However since many
      foods are warmed, it is important that the thermostability of the enzymes be
      assessed. This paper provides data on the stability of alpha -galactosidase,
      which could potentially be added to food matrices containing stachyose or
      raffinose, such as beans. 

PMID- 24744925
TI  - A Rare Localization of Ectopic Pregnancy: Intramyometrial Pregnancy in Twin
      Pregnancy following IVF.
AB  - Intramyometrial pregnancy is a rare form of ectopic pregnancy. It makes a
      diagnostic and therapeutic challenge. If misdiagnosed the intramyometrial
      pregnancy can cause a uterine rupture and become life-threatening condition. We
      report a case of intramyometrial pregnancy in twin pregnancy following IVF with
      spontaneous abortion of the first twin At 9 weeks of gestation. The 10 weeks scan
      showed a normal fetus which was described to be highly localized in the uterus
      but the diagnosis of intramyometrial pregnancy was not suspected. The patient was
      admitted at 14 weeks of gestation with pelvic pain, hemorrhage, and shock. She
      was operated and the diagnosis of ruptured intramyometrial pregnancy was done and
      managed conservatively. This case illustrates the diagnostic difficulties of
      intramyometrial pregnancy. We discuss pathophysiology, diagnosis, and treatment
      of this exceptional form of ectopic pregnancy. 

PMID- 24744926
TI  - Choroidal metastasis from follicular cell thyroid carcinoma masquerading as
      circumscribed choroidal haemangioma.
AB  - Choroidal metastases from follicular thyroid carcinoma are uncommon and usually
      present as an amelanotic lesion against a background of known systemic disease.
      We present the case of a 56-year-old woman with a thyroid metastatic focus with
      unusual clinical presentation, systemic involvement, and early response to
      systemic treatment. A review of the literature accompanies this case
      presentation. 

PMID- 24744927
TI  - An innocent appearing subcutaneous nodule diagnoses a small cell lung cancer in a
      never-smoker female.
AB  - Lung cancer among never-smokers is recognized as the 7th most common cause of
      cancer death globally. Adenocarcinoma is the most commonly reported histology.
      Small cell lung cancer (SCLC) has the strongest association with smoking and is
      rarely reported in never-smokers. Although lung cancer in never-smokers is more
      common in women, the overall incidence of SCLC in female never-smokers still
      remains low. Soft tissue metastases from any cancer are rare with an overall
      prevalence of 1.8%. Soft tissue metastases from lung primary are uncommon, mostly
      from adenocarcinoma, and portend a poor prognosis. Cutaneous metastases from SCLC
      are exceptionally rare with reported incidence of 0.3% to 0.8%. We believe ours
      is the first reported case of SCLC presenting as subcutaneous nodule, in a never
      smoker, otherwise asymptomatic female. The diagnosis of SCLC was made
      incidentally by the excisional biopsy of the subcutaneous nodule. Subsequent CT
      chest and PET scan revealed a hypermetabolic right lower lobe spiculated lung
      mass with adrenal and liver involvement. Platinum and etoposide chemotherapy with
      prophylactic cranial irradiation was initiated for advanced SCLC, and she
      required further irinotecan and taxol for subsequent pancreatic and adrenal
      metastases. With continued deterioration, she died approximately 36 months from
      diagnosis, while under hospice care. 

PMID- 24744929
TI  - Oligodendroglioma arising in mature cystic teratoma.
AB  - Background. Development of neuroepithelial tumors from mature cystic teratoma is
      very rare. We present a case of oligodendroglioma developing inside mature cystic
      teratoma. Case. Eighteen-years-old female, right adnexal mass with solid and
      cystic areas was detected. Sections showed all three germ layers. Also, a tumoral
      lesion was observed in a glial fibrillary matrix. Tumor was composed of
      monotonous, uniform cells which have oval-round nucleus, perinuclear halo, and
      indistinct cytoplasm. GFAP, EGFR, P53 were positive. Conclusions. We diagnosed
      oligodendroglioma arising from mature cystic teratoma. There was no recurrence at
      the end of 13 months followup. The number of cases which have been reported in
      the literature is only a few. 

PMID- 24744928
TI  - Multiple cutaneous angiosarcomas after breast conserving surgery and bilateral
      adjuvant radiotherapy: an unusual case and review of the literature.
AB  - Breast angiosarcomas (BAs) are rare but serious events that may arise after
      radiation exposure. Disease outcome is poor, with high risk of local and distant
      failure. Recurrences are frequent also after resection with negative margins. The
      spectrum of vascular proliferations associated with radiotherapy in the setting
      of breast cancer has expanded, including radiation-associated atypical vascular
      lesions (AVLs) of the breast skin as a rare, but well-recognized, entity.
      Although pursuing a benign behavior, AVLs have been regarded as possible
      precursors of postradiation BAs. We report an unusual case of a 71-year-old woman
      affected by well-differentiated bilateral cutaneous BA, diagnosed 1.9 years after
      adjuvant RT for synchronous bilateral breast cancer. Whole-life clinical followup
      is of crucial importance in breast cancer patients. 

PMID- 24744930
TI  - Management of a patient with metastatic colorectal cancer and liver metastases.
AB  - Liver metastases are commonly encountered in patients presenting with metastatic
      colorectal cancer (mCRC); resection is the treatment of choice. A number of
      systemic treatment options are currently available for such patients, including
      the use of 5-fluorouracil-based chemotherapies and oxaliplatin (e.g., FOLFOX) in
      combination with biologic agents that target angiogenesis (e.g., bevacizumab).
      For patients with progression following first-line treatment, current second-line
      options include a change in chemotherapy with bevacizumab (for patients who did
      or did not receive prior bevacizumab) or FOLFIRI in combination with aflibercept,
      a more recently approved antiangiogenesis therapy. Neurotoxicity is a well
      established adverse event of oxaliplatin-based therapy. The current case details
      an mCRC patient with liver metastases who was treated with a capecitabine and
      oxaliplatin regimen (XELOX), and experienced two episodes of transient cortical
      blindness possibly related to oxaliplatin. After disease progression, the patient
      was switched to a regimen of FOLFIRI and aflibercept and did well on this second
      line regimen. 

PMID- 24744931
TI  - Lung Metastasis after an Eighteen-Years-Long Disease-Free Period since Uterine
      Leiomyosarcoma Diagnosis.
AB  - Uterine leiomyosarcoma (ULMS) is an uncommon malignancy that accounts for one
      third of uterine sarcomas and represents 1% of all uterine malignancies, with an
      incidence averaging 0.5-1/100,000/year. The prognosis is poor due to its
      intrinsic aggressiveness and its characteristic high metastatic potential with
      reported distant metastatic spread in lung, abdomen, soft tissue, and brain. We
      present the case of a 67-year-old woman with lung metastasis after eighteen years
      since uterine leiomyosarcoma diagnosis and its following surgical resection. The
      diagnosis of pulmonary metastases was obtained by reviewing the histology of the
      previous uterine tumor: the tumor cells were immunoreactive for CD10, PR, and
      smooth muscle actin (SMA), but negative for desmin, S100, CD34, CD 117,
      cytokeratins AE1AE3, CD68R, and ER. To our knowledge, this disease-free interval
      is the longest among previous reports of pulmonary metastasis of uterine
      leiomyosarcoma. 

PMID- 24744932
TI  - Spontaneous closure of a fully developed macular hole in a severely myopic eye.
AB  - Purpose. Myopic macular holes can be difficult to close with surgery and are
      frequently associated with retinal detachment. We report on a case of a macular
      hole in a severely myopic eye that underwent spontaneous closure. Methods. An
      observational case study. Results. A 55-year-old female was referred to
      Ophthalmology for a central scotoma and metamorphopsia in the right eye. Visual
      acuity was 1/20 in both eyes. Fundus examination showed loss of the foveal
      depression, with a small yellow ring in the center of the fovea in the right eye,
      and a tilted optic disc and peripapillary staphyloma bilaterally. Spectral domain
      optical coherence tomography (SD-OCT) revealed a fully developed macular hole
      with a rim of thickened and slightly elevated retina in the right eye. The
      patient refused surgery. After 4 years of follow-up, her visual acuity improved
      to 20/40 in the right eye, and SD-OCT revealed spontaneous sealing of the macular
      hole without bare retinal pigment epithelium. Conclusions. Myopic macular holes
      represent a challenge regarding their management, and the prognosis is often
      poor. 

PMID- 24744933
TI  - Recurrent bilateral occipital infarct with cortical blindness and anton syndrome.
AB  - Bilateral cortical blindness and Anton syndrome, are most commonly caused by
      ischaemic stroke. In this condition, patients have loss of vision but deny their
      blindness despite objective evidence of visual loss. We report a case of a
      patient with multiple cardiovascular risk factors who developed recurrent
      bilateral occipital lobe infarct with Anton syndrome. A suspicion of this
      condition should be raised when the patient has denial of blindness in the
      presence of clinical and radiological evidence of occipital lobe injury.
      Management of this condition should focus on the underlying cause, in which our
      patient requires secondary stroke prevention and rehabilitation. 

PMID- 24744934
TI  - Pott's Disease in a 2-Year-Old Child Treated by Decompression and Anterior
      Posterior Instrumented Fusion.
AB  - Introduction. Paraplegia and kyphotic deformity are two major disease-related
      problems of spinal tuberculosis, especially in the early age disease. In this
      study a 2-year-old boy who underwent surgical decompression, correction, and 360
      degrees  instrumented fusion via simultaneous anterior-posterior technique for
      Pott's disease was reported. Case Report. A 2-year-and-9-month-old boy presented
      with severe back pain and paraparesis of one-month duration. Thoracic magnetic
      resonance imaging demonstrated destruction with a large paraspinal abscess
      involving T5-T6-T7 levels, compressing the spinal cord. The paraspinal abscess
      drained and three-level corpectomy was performed at T5-6-7 with transthoracic
      approach. Anterior instrumentation and fusion was performed with structural 1
      autogenous fibula and rib graft using screw-rod system. In prone position pedicle
      screws were inserted at T4 and T8 levels and rods were placed. Six months after
      surgery, there was no weakness or paraparesis and no correction loss at the end
      of follow-up period. Discussion. In cases of vertebral osteomyelitis with severe
      anterior column destruction in the very early child ages the use of anterior
      structural grafts and instrumentation in combination with posterior
      instrumentation is safe and effective in maintenance of the correction achieved
      and allows efficient stabilization and early mobilization. 

PMID- 24744935
TI  - Chondroid syringoma of the medial canthus.
AB  - Chondroid syringoma, or pleomorphic adenoma of the skin, is a rare, benign skin
      adnexal tumor. It is usually exhibited as a slowly growing intradermal or
      subcutaneous nodule, typically located in the head and neck region. Because of
      the unremarkable clinical symptomatology of this rare tumor, the diagnosis is
      exclusively made retrospectively based on histological confirmation of the
      surgically excised tumor. We present a rare case of a chondroid syringoma located
      in the left medial canthus of a 58-year-old man. The patient had no symptoms and
      decided to excise it for cosmetic reasons only. Local excision with a macroscopic
      wide cuff of normal tissue was done, without destroying the aesthetic and
      functional structures, since the defect was restored by a finger flap. One year
      postoperatively, the patient has remained disease-free. Chondroid syringoma
      usually appears in the face but the location in the medial canthus is not
      mentioned in the literature for the last twenty years. 

PMID- 24744936
TI  - Malignant peripheral nerve sheath tumour of the maxilla.
AB  - A 38-year-old man was diagnosed with malignant peripheral nerve sheath tumour of
      the maxilla. He was treated with total maxillectomy. Histopathological
      examination of the resected specimen revealed a close resection margin. The
      tumour was of high grade with an MIB-1 labelling index of almost 60%. At six
      weeks following the surgery, he developed local tumour relapse. The patient
      succumbed to the disease at five months from the time of diagnosis. The present
      report underlines the locally aggressive nature of malignant peripheral nerve
      sheath tumour of the maxilla which necessitates an early therapeutic
      intervention. A complete resection with clear margins is the most important
      prognostic factor for malignant peripheral nerve sheath tumour in the head and
      neck region. Adjuvant radiotherapy may be considered to improve the local
      control. Future research may demarcate the role of targeted therapy for patients
      with malignant peripheral nerve sheath tumour. 

PMID- 24744937
TI  - Cylindroma with Stromal Adipose Tissue Metaplasia versus Arising in a Background
      of Nevus Lipomatosus.
AB  - Nevus lipomatosus superficialis is a rare type of connective tissue nevus.
      Cylindroma is a benign skin appendage tumor with a predilection for the scalp of
      older females. We describe the case of a 56-year-old woman with a scalp lesion
      demonstrating histopathologic features consistent with benign cylindroma arising
      within a nevus lipomatosus superficialis. To our knowledge, this lesion has not
      been raised in the literature in the differential for cylindroma with what is
      presumed to be stromal adipose metaplasia. 

PMID- 24744938
TI  - Bilateral spontaneous pneumothorax in chronic silicosis: a case report.
AB  - Silicosis is an occupational lung disease caused by inhalation of crystalline
      silica. People working in occupations like sandblasting, surface drilling,
      tunneling, silica flour milling, ceramic making, and so forth are predisposed to
      develop silicosis. Crystalline forms of silica are more fibrogenic than the
      amorphous forms, highlighting the importance of the physical form in
      pathogenesis. Lung biopsy is rarely performed for the diagnosis of silicosis as
      it can easily be detected by occupational history and radiological features.
      Patients with silicosis can develop complications like tuberculosis, lung cancer,
      progressive massive fibrosis, cor pulmonale, broncholithiasis, or
      tracheobronchial compression by lymph nodes. Pleural involvement in silicosis is
      rare. Spontaneous pneumothorax is a pleural complication that can develop in such
      patients. Usually in silicosis pneumothorax is unilateral. We hereby report the
      lung biopsy findings and discuss the mechanism of pneumothorax development in a
      case of chronic silicosis who, later on died during the course of the disease. 

PMID- 24744939
TI  - Development of Localized Pulmonary Interstitial Emphysema in a Late Preterm
      Infant without Mechanical Ventilation.
AB  - Pulmonary interstitial emphysema (PIE) is not an uncommon finding in premature
      infants with respiratory distress who need respiratory support by mechanical
      ventilation. PIE has been reported in a few cases of neonates in whom either no
      treatment other than room air was given or they were given continuous positive
      end-expiratory pressure (CPAP) support. We present a case of a premature neonate
      who presented with respiratory distress, in whom PIE and spontaneous pneumothorax
      (PTX) developed while on CPAP therapy only. The patient was treated
      conservatively with subsequent resolution of the radiological findings and
      clinical improvement. No surgical intervention was required. It is important to
      know that PIE may develop independently of mechanical ventilation. We would like
      to add this case to the literature and describe the pertinent plain film and
      computed tomography (CT) findings of this entity, the possible mechanism of
      development, and the differential diagnosis. A review of the literature is also
      provided. 

PMID- 24744940
TI  - Nonconvulsive status epilepticus complicating epstein-barr virus encephalitis in
      a child.
AB  - Children with acute encephalopathy show prolonged electrographic seizure activity
      consistent with nonconvulsive status epilepticus (NCSE). Pediatric NCSE is a
      heterogeneous clinical entity with poor outcome and different etiologies,
      including central nervous system infection, stroke, toxic-metabolic syndrome, and
      epileptic syndrome. We report a 4-year-old girl with seizure and behavioral
      changes in whom the analysis of cerebrospinal fluid by polymerase chain reaction
      was positive for Epstein-Barr virus. We emphasize the importance of
      electroencephalography (EEG), and particularly, of continuous EEG monitoring for
      early recognition and appropriate treatment of this condition. 

PMID- 24744941
TI  - 31-year-old female shows marked improvement in depression, agitation, and panic
      attacks after genetic testing was used to inform treatment.
AB  - This case describes a 31-year-old female Caucasian patient with complaints of
      ongoing depression, agitation, and severe panic attacks. The patient was
      untreated until a recent unsuccessful trial of citalopram followed by venlafaxine
      which produced a partial response. Genetic testing was performed to assist in
      treatment decisions and revealed the patient to be heterozygous for polymorphisms
      in 5HT2C, ANK3, and MTHFR and homozygous for a polymorphism in SLC6A4 and the low
      activity (Met/Met) COMT allele. In response to genetic results and clinical
      presentation, venlafaxine was maintained and lamotrigine was added leading to
      remission of agitation and depression. 

PMID- 24744942
TI  - Delivery induced intraperitoneal rupture of a cystic ovarian teratoma and
      associated chronic chemical peritonitis.
AB  - Intraperitoneal rupture of cystic ovarian teratoma is a rare complication. We
      report a case in a 29-year-old female, with increased abdominal circumference 2
      months after vaginal delivery. MRI/CT raised this diagnosis associated to
      chemical peritonitis. A malignant ovarian mass with peritoneal carcinomatosis was
      excluded. Laparoscopic oophorectomy was performed and histologic analysis
      confirmed imaging findings. This case demonstrates the interest of imaging before
      surgery in pelvic masses to avoid misdiagnosing and to provide adequate
      treatment. 

PMID- 24744943
TI  - Vascular plug-assisted retrograde transvenous obliteration of portosystemic
      shunts for refractory hepatic encephalopathy: a case report.
AB  - While balloon-assisted retrograde transvenous obliteration (BRTO) has been used
      for two decades in Asia for the management of gastric variceal bleeding, it is
      still an emerging therapy elsewhere. Given the shunt closure brought about by the
      procedure, BRTO has also been used for the management of portosystemic
      encephalopathy with promising results. Modified versions of BRTO have been
      developed, including plug-assisted retrograde transvenous obliteration (PARTO),
      where a vascular plug is deployed within a portosystemic shunt. To our knowledge,
      we present the first North American case of PARTO in the setting of a large
      splenorenal shunt for the management of portosystemic encephalopathy. 

PMID- 24744944
TI  - A pilocytic astrocytoma mimicking a clinoidal meningioma.
AB  - Pilocytic astrocytomas and meningiomas are benign, primary brain tumors that may
      involve the optic tract. Classically, the presence of a dural "tail" sign may
      differentiate a meningioma from other intracranial lesions. In this report, we
      describe a mass with the typical appearance of a clinoidal meningioma on magnetic
      resonance imaging (MRI) but postoperatively diagnosed as a pilocytic astrocytoma.
      This case illustrates the rare occurrence of a pilocytic astrocytoma mimicking a
      meningioma on MRI. 

PMID- 24744945
TI  - A case of neurosarcoidosis with labyrinthine involvement.
AB  - Sarcoidosis is a chronic granulomatous disease of unknown aetiology, which may
      involve any organ system. It most commonly occurs in adults with childhood
      involvement being rare. Central nervous system involvement is seen in up to 25%
      and typically involves meningeal disease resulting in multiple cranial
      neuropathies. Other common clinical findings include seizures, headache,
      dementia, and pituitary dysfunction. Imaging plays a central role in the
      diagnosis with typical findings including pachymeningeal and leptomeningeal
      enhancing lesions. Other imaging findings include lacunar and major territory
      infarcts, hypothalamic and infundibular thickening, hydrocephalus, and cranial
      nerve enhancement. We present a case of an eight-year-old male patient with
      progressive headache, visual disturbance, unilateral sensory hearing loss, and
      multiple cranial neuropathies. Imaging findings demonstrated the classic
      pachymeningeal and leptomeningeal enhancement along much of the skull base, as
      well as enhancement of the right and left second and eighth cranial nerves.
      Extensive inflammatory changes were noted in the temporal bones and paranasal
      sinuses. There was also enhancement of the right and left labyrinths. Sinus
      biopsy confirmed sarcoidosis. We present the first case to our knowledge of
      sarcoid labyrinthitis. 

PMID- 24744946
TI  - Multimodality imaging evaluation of an uncommon entity: esophageal heterotopic
      pancreas.
AB  - A 25-year-old male was referred to the Radiology Department with new onset of
      right upper quadrant and epigastric abdominal pain. He had no past medical or
      surgical history. Physical exam was unremarkable. The patient underwent computed
      tomography (CT), fluoroscopic upper gastrointestinal (GI) evaluation, endoscopic
      ultrasound (EUS), and positron emission tomography (PET) evaluation, revealing
      the presence of a heterogeneous esophageal mass. In light of imaging findings and
      clinical workup, the patient was ultimately referred for thorascopic surgery.
      Surgical findings and histology confirmed the diagnosis of esophageal heterotopic
      pancreas. 

PMID- 24744947
TI  - Amyloidoma, an unusual cause of fracture.
AB  - We report a case of a spontaneous hip fracture in a context of dysglobulinemia.
      The bone histologic examination found amyloidoma. Amyloidoma is an overload
      pathology and an unusual cause of fracture. In most of the cases, it is
      associated with myeloma and the difference between bone invasion of myeloma and
      amyloidoma in an osteolytic radiographic picture is not easy but is of importance
      because prognosis and treatment may be totally different. Thus, in the context of
      dysglobulinemia, one must keep in mind that spontaneous bone fracture may be due
      to amyloidoma with another prognosis. 

PMID- 24744948
TI  - A rare case of perforated descending colon cancer complicated with a fistula and
      abscess of left iliopsoas and ipsilateral obturator muscle.
AB  - Perforation of descending colon cancer combined with iliopsoas abscess and
      fistula formation is a rare condition and has been reported few times. A 67-year
      old man came to our first aid for an acute pain in the left iliac fossa, in the
      flank, and in the ipsilateral thigh. Ultrasonography and computed tomography
      revealed a left abdominal wall, retroperitoneal, and iliopsoas abscess that also
      involved the ipsilateral obturator muscle. It proceeded with an exploratory
      laparotomy that showed a tumor of the descending colon adhered and perforated in
      the retroperitoneum with abscess of the iliopsoas muscle on the left-hand side,
      with presence of a fistula and liver metastases. A left hemicolectomy with
      drainage of the broad abscess was performed. Pathologic report findings
      determined adenocarcinoma of the resected colon. 

PMID- 24744949
TI  - Idiopathic thrombocytopenic purpura after mastectomy and axillary lymph node
      dissection.
AB  - First described in 1916, idiopathic thrombocytopenic purpura (ITP) is an
      autoimmune disease resulting in the destruction of platelets. Here, we present a
      case of an 85-year-old patient diagnosed with invasive ductal carcinoma of the
      breast whose surgical treatment was complicated postoperatively by acute-onset
      thrombocytopenia with a resultant hematoma at the operative site. Diagnostic
      Workup revealed no clear etiology for the thrombocytopenia; therefore, a
      presumptive diagnosis of idiopathic thrombocytopenic purpura was made. Previous
      literature has associated the development of idiopathic thrombocytopenic purpura
      with breast cancer. However, to the authors' knowledge, there are no reported
      cases of ITP presenting immediately following surgical intervention for breast
      cancer in the absence of other etiologic factors. 

PMID- 24744950
TI  - Functional recovery in chronic stage of spinal cord injury by neurorestorative
      approach: a case report.
AB  - Spinal cord injury (SCI) at an early age can be debilitating for the child's
      growth. Current treatments show a level of stagnancy, after which the recovery is
      minimal. Cellular therapy is an emerging area of research and has been found to
      possess many benefits in the previous studies. Transplantation of autologous bone
      marrow mononuclear cells (BMMNCs) has demonstrated therapeutic potential for many
      neurological conditions, including spinal cord injury. Here we report a case of 6
      year-old girl with traumatic SCI at the level of C7-D1 4 years back, who
      underwent 2 doses of cell transplantation with autologous BMMNCs with an interval
      of 6 months along with standard rehabilitation. The patient did not have any
      major or minor side effects. The patient showed clinical improvements throughout
      the 6 months after transplantation, which was assessed using Functional
      Independence Measure (before: 82, after: 101 out of 126). There were patchy areas
      of sensory gain in bilateral feet recorded, with improvements in the bladder
      sensation and control. Improved gait was seen as a result of better strength in
      abdominals and back extensors. The fact that there was functional improvement in
      the chronic plateau phase indicates the potential of cell therapy in chronic SCI.
      Further clinical studies are warranted. 

PMID- 24744951
TI  - A rare case of paratesticular leiomyosarcoma.
AB  - Paratesticular leiomyosarcomas are rare and can lead to significant morbidity and
      mortality, if inadequately diagnosed or treated. We present a case of
      paratesticular leiomyosarcoma in an 88-year-old man presenting with a left
      scrotal mass with ultrasound revealing that the mass is extratesticular. Left
      radical orchidectomy was performed and pathological examination of the resected
      specimen confirmed the diagnoses of high grade leiomyosarcoma with surgical
      margins clear of tumour. The patient was free of metastatic disease on further
      imaging and has been disease-free for 18 months. A review of the literature
      regarding paratesticular leiomyosarcoma presentation, diagnosis, and treatment is
      also discussed. 

PMID- 24744952
TI  - Dabigatran induced hemorrhagic cystitis in a patient with painful bladder
      syndrome.
AB  - An 82-year-old female presented with longstanding history of both painful bladder
      syndrome and atrial fibrillation. She underwent hydrodistension remarkable for
      hematuria without temporary discontinuation of Dabigatran. Subsequently, patient
      was admitted to the hospital secondary to anemia and hemorrhagic cystitis. 

PMID- 24744953
TI  - Giant idiopathic pulmonary artery aneurysm: an interesting incidental finding.
AB  - Idiopathic pulmonary artery aneurysm is a rare condition. This type of aneurysm
      can be presented with noncardiac symptoms or even asymptomatic. We report a 73
      year-old man with a gigantic idiopathic pulmonary artery aneurysm which was
      referred to our unit for his kidney problems. During his workup we incidentally
      found the aneurysm by an abnormal chest-X ray and auscultation. Our further
      evaluations revealed a 9.8 cm aneurysm in transthoracic echocardiography. 

PMID- 24744954
TI  - Transcatheter coil embolization of a coronary artery-left ventricular fistula
      associated with single coronary artery anomaly.
AB  - Single coronary artery anomaly associated with coronary fistula is a rare entity.
      Transcatheter coil embolization is the treatment of choice for coronary artery
      fistulas. In this case report, we describe a patient with both single coronary
      artery anomaly and coronary fistula who was successfully treated with coil
      embolization. 

PMID- 24744955
TI  - Maternal hypothyroidism in early pregnancy and infant structural congenital
      malformations.
AB  - Background. The question is debated on whether maternal hypothyroidism or use of
      thyroxin in early pregnancy affects the risk for infant congenital malformations.
      Objectives. To expand the previously published study on maternal thyroxin use in
      early pregnancy and the risk for congenital malformations. Methods. Data from the
      Swedish Medical Birth Register were used for the years 1996-2011 and infant
      malformations were identified from national health registers. Women with
      preexisting diabetes or reporting the use of thyreostatics, anticonvulsants, or
      antihypertensives were excluded from analysis. Risk estimates were made as odds
      ratios (ORs) or risk ratios (RRs) after adjustment for year of delivery, maternal
      age, parity, smoking, and body mass index. Results. Among 23 259 infants whose
      mothers in early pregnancy used thyroxin, 730 had a major malformation; among all
      1 567 736 infants, 48012 had such malformations. The adjusted OR was 1.06 (95% CI
      0.98-1.14). For anal atresia the RR was 1.85 (95% CI 1.00-1.85) and for choanal
      atresia 3.14 (95% CI 1.26-6.47). The risk of some other malformations was also
      increased but statistical significance was not reached. Conclusions. Treated
      maternal hypothyroidism may be a weak risk factor for infant congenital
      malformations but an association with a few rare conditions is possible. 

PMID- 24744956
TI  - Neuropsychiatric symptoms in an inpatient Parkinson's disease sample.
AB  - Background. Neuropsychiatric symptoms are common in idiopathic Parkinson's
      disease (PD), and hospitalization for delirium, depression, psychosis, and
      anxiety is sometimes required. A minimal amount of data exists on these patients.
      Methods. Charts of all patients admitted to a psychiatric hospital between 2006
      and 2009 with a diagnosis of PD were reviewed. Forty-three met entry criteria and
      were reviewed. Initial and discharge diagnoses, comorbid psychiatric diagnoses,
      length of stay, and living arrangements before and after hospitalization are
      described. Results. Consistent with previous research, this study showed evidence
      of comorbid psychiatric disorders within PD. Conclusions. The long-term goal of
      this area of study would be to reduce neuropsychiatric symptoms and improve
      quality of life in order to reduce inpatient hospital stays. 

PMID- 24744957
TI  - Morphological changes in the bone marrow of the dogs with visceral leishmaniasis.
AB  - The aim of this study was to evaluate the most frequent lesions in the bone
      marrow of dogs naturally infected by Leishmania (Leishmania) chagasi. Thirty
      three dogs sacrificed at the Zoonosis Control Center of Aracatuba, a municipality
      endemic for visceral leishmaniasis (VL), were used. The animals were classified
      as asymptomatic, oligosymptomatic, and symptomatic groups. At the necropsy, bone
      marrow samples were collected from the femur, fixed, processed, and stained with
      hematoxylin and eosin. The lesion intensity was classified as mild, moderate, or
      severe. The parasite load was determined using immunohistochemistry. The most
      important lesions consisted of multifocal to diffuse granulomas, megakaryocytic
      dysplasia, and medullary aplasia. There were no statistical differences between
      the three clinical groups regarding parasite load and lesion intensity.
      Asymptomatic dogs also presented high parasitism in the bone marrow as dogs with
      clinical signs of VL. It was concluded that, regardless of clinical group, the
      bone marrow is a site for multiplication of Leishmania chagasi. Possibly, the
      bone marrow dysplasia may arise from the presence of many parasitized and
      activated macrophages in this organ. Consequently, it affects the profile of
      hematopoietic cells in the bone marrow and systemic circulation. 

PMID- 24744958
TI  - Esophagojejunostomy feeding tube placement in 5 dogs with pancreatitis and
      anorexia.
AB  - Enteral feeding tube placement has been described in veterinary medicine for
      several years. Indications include oral, esophageal, gastrointestinal,
      pancreatic, hepatic, and neurologic diseases. In this paper, endoscopically
      assisted placement of an esophagojejunostomy (EJ) feeding tube in dogs with
      pancreatitis and prolonged anorexia is described. To the author's knowledge there
      are no published reports of this procedure. Esophagojejunostomy feeding tubes
      provide an alternative to other forms of postgastric feeding tube placement
      (e.g., nasojejunal, gastrojejunostomy, and jejunostomy tubes) without the
      associated complications of patient discomfort, sneezing, epistaxis, and
      peritonitis. Tube occlusion, transient vomiting and loose stool were the most
      commonly reported complications. 

PMID- 24744959
TI  - In Vitro Virucidal and Virustatic Properties of the Crude Extract of Cynodon
      dactylon against Porcine Reproductive and Respiratory Syndrome Virus.
AB  - The in vitro virustatic and virucidal tests of the crude extract of Cynodon
      dactylon against infection with porcine reproductive and respiratory syndrome
      virus (PRRSV), a cause of major devastating pig disease, were described. Crude
      extract of C. dactylon was prepared for cytotoxicity on tissue-culture cells that
      were used to measure virustatic and virucidal activities against PRRSV. Crude
      extract of C. dactylon at 0.78 mg/mL showed no cytotoxicity on the cell line, and
      at that concentration significantly inhibited replication of PRRSV as early as 24
      hours post infection (hpi). C. dactylon also inactivated PRRSV as determined by
      immunoperoxidase monolayer assay (IPMA) compared to the control experiments. In
      summary, the present study may be among the earliest studies to describe
      virustatic and virucidal activities of C. dactylon crude extract against PRRSV in
      vitro. Extracts of C. dactylon may be useful for PRRSV control and prevention on
      pig farms. 

PMID- 24744960
TI  - Using the Doubly Charged Selected Ion Coupled with MS/MS Fragments Monitoring
      (DCSI-MS/MS) Mode for the Identification of Gelatin Species.
AB  - In electrospray ionization (ESI) mode, peptides and proteins can be multiply
      charged ions; in this situation a doubly charged selected ion (DCSI) coupled with
      mass spectrometry (MS/MS) fragments monitoring (DCSI-MS/MS) method is the most
      suitable scanning mode to detect known peptides in complex samples when an ion
      trap mass spectrometer is the instrument used for the analysis. In this mode, the
      MS detector is programmed to only select a doubly charged ion as a precursor and
      to perform continuous MS/MS on one or more of the selected precursors, either
      during a specific time interval or along the whole chromatographic run. Gelatin
      is a mixture of high molecular weight polypeptides from the hydrolysis of
      collagen. In this study, the DCSI-MS/MS monitoring mode was applied to the
      detection of previously characterized species-specific peptides from different
      gelatins. The proposed methodology makes use of tryptic digestion for sample
      preparation and peptide separation and identification by rapid resolution liquid
      chromatography coupled to an ion trap working in the DCSI-MS/MS mode for the
      analysis. This methodology was applied to the differential classification of five
      commercial, homological species of gelatins and proved to be an excellent tool
      for gelatin product authentication. 

PMID- 24744961
TI  - One single amino Acid for estimation the content of total free amino acids in
      qingkailing injection using high-performance liquid chromatography-diode array
      detection.
AB  - Qingkailing injection (QKLI), a modern traditional Chinese medicine preparation,
      has been widely used in clinics due to its fast and significant efficacy in
      treatment of high fever. The free amino acids (AAs) were considered to be the
      most abundant active ingredients indisputably. So developing an accurate and
      simple determination method to measure the contents of total free AAs in QKLI is
      very crucial. In current study, the accurate and simple method of using one
      single standard AA for simultaneous quantification of multiple AAs (One for M) in
      QKLI was developed. Particularly, the calculation methods and the robustness of
      relative correction factors (RCFs) were investigated systematically. No
      statistically significant difference between these two quantification methods of
      One for M and classic regression equation was found by the t-test (P  =  95%, P >
      0.05). The results showed that the precision (RSD < 4.88%), the robustness (RSD <
      4.04%), and the average recoveries (94.11%-107.94%) of this newly proposed method
      all met the requirements for content determination. This One for M method will
      provide a scientific reference for the quantitative determination of AAs in other
      traditional Chinese medicines and their preparations owing to its accuracy and
      simplicity. 

PMID- 24744962
TI  - Mapping rare erythrocyte phenotypes in morocco: a tool to overcome transfusion
      challenges.
AB  - The aim of this research is to search for the distribution of blood groups in all
      the regions of Morocco. This study, done for the first time, aimed to provide the
      frequency of the Rhesus system and Kell (K) in more than 55000 blood donors from
      nine different regions around the country. In addition, the frequency of the
      Cellano, Duffy, Kidd, and MNS blood antigens was searched for 500 blood donors
      from the Rabat's region. Frequency of blood donors with rare blood groups was
      characterized for the first time in the country and compared to results found
      from other populations. 

PMID- 24744963
TI  - An Ungrounded Hand-Held Surgical Device Incorporating Active Constraints with
      Force-Feedback.
AB  - This paper presents an ungrounded, hand-held surgical device that incorporates
      active constraints and force-feedback. Optical tracking of the device and
      embedded actuation allow for real-time motion compensation of a surgical tool as
      an active constraint is encountered. The active constraints can be made soft, so
      that the surgical tool tip motion is scaled, or rigid, so as to altogether
      prevent the penetration of the active constraint. Force-feedback is also provided
      to the operator so as to indicate penetration of the active constraint boundary
      by the surgical tool. The device has been evaluated in detailed bench tests to
      quantify its motion scaling and force-feedback capabilities. The combined effects
      of force-feedback and motion compensation are demonstrated during palpation of an
      active constraint with rigid and soft boundaries. A user study evaluated the
      combined effect of motion compensation and force-feedback in preventing
      penetration of a rigid active constraint. The results have shown the potential of
      the device operating in an ungrounded setup that incorporates active constraints
      with force-feedback.

PMID- 24744964
TI  - Hyperdense endobronchial mass - a rare manifestation of metastatic melanoma.
AB  - Parenchymal lung metastases are common in malignant melanoma. However,
      endobronchial metastatic melanoma is uncommon. In this report, we describe a
      patient with a hyperdense endobronchial mass diagnosed as a melanoma metastasis.
      We review the imaging findings of pulmonary metastatic melanoma and discuss the
      differential diagnosis of an endobronchial mass in adults. 

PMID- 24744965
TI  - Pulmonary hyalinizing granuloma associated with idiopathic thrombocytopenic
      purpura.
AB  - Pulmonary hyalinizing granuloma (PHG) is a rare, benign lung disease of unknown
      etiology. It manifests as discrete, rounded nodules within the lung parenchyma. A
      39-year-old woman presented for investigation after pulmonary nodules were found
      incidentally. Chest computed tomography showed multiple, discrete, non-enhancing
      pulmonary nodules bilaterally. Positron emission tomography (PET) was negative.
      Biopsy demonstrated a non-specific lymphoplasmacytic infiltrate. Open resection
      yielded two nodules consistent with hyalinizing granulomas. The differential for
      multiple pulmonary nodules is broad. PET scan can help rule out metastatic
      disease, although some cancers are not hypermetabolic on PET. Furthermore, some
      non-malignant conditions, including hyalinizing granuloma, can show increased
      activity on PET. PHG should be included in the differential of multiple pulmonary
      nodules, especially if nodule stability can be demonstrated and/or needle
      biopsies are non-diagnostic. Associated immune-mediated conditions, such as
      idiopathic thrombocytopenic purpura (ITP) in our patient, may also favor HG. In
      this case report we find an association between PHG and ITP. 

PMID- 24744966
TI  - Initial experience with combination digital breast tomosynthesis plus full field
      digital mammography or full field digital mammography alone in the screening
      environment.
AB  - OBJECTIVES: Initial review of patients undergoing screening mammography imaged
      with a combination of digital breast tomosynthesis (DBT) plus full field digital
      mammography (FFDM) compared with FFDM alone. MATERIALS AND METHODS: From June
      2011 to December 2011, all patients presenting for routine screening mammography
      were offered a combination DBT plus FFDM exam. Under institutional review board
      approval, we reviewed 524 patients who opted for combination DBT plus FFDM and
      selected a sample group of 524 FFDM screening exams from the same time period for
      a comparative analysis. The chi(2) (Chi-square) test was used to compare recall
      rates, breast density, personal history of breast cancer, and family history of
      breast cancer between the two groups. RESULTS: Recall rate for FFDM, 11.45%, was
      significantly higher (P < 0001) than in the combination DBT plus FFDM group
      (4.20%). The biopsy rate in the FFDM group was 2.29% (12/524), with a cancer
      detection rate of 0.38% (2/524, or 3.8 per 1000) and positive predictive value
      (PPV) of 16.7% (2/12). The biopsy rate for the DBT plus FFDM group was 1.14% (n =
      6/524), with a cancer detection rate 0.57% (n = 3/524, or 5.7 per 1000) and PPV
      of 50.0% (n = 3/6). Personal history of breast cancer in the FFDM group was
      significantly lower (P < 0.0001) than in the combination DBT plus FFDM group;
      2.5% and 5.7%, respectively. A significant difference in family history of breast
      cancer (P < 0.0001) was found, with a higher rate in the combination DBT plus
      FFDM group (36.0% vs. 53.8%). There was a significant difference between the
      combination DBT plus FFDM group and FFDM alone group, when comparing breast
      density (P < 0.0147, 61.64% vs. 54.20% dense breasts, respectively) with a higher
      rate of dense breasts in the DBT plus FFDM group. In follow-up, one cancer was
      detected within one year of normal screening mammogram in the combination DBT
      plus FFDM group. CONCLUSION: Our initial experience found the recall rate in the
      combination DBT plus FFDM group was significantly lower than in the FFDM alone
      group, despite the fact that the combination DBT plus FFDM group had additional
      risk factors.

PMID- 24744967
TI  - Role of Perfusion CT Differentiating Hemangiomas from Malignant Hepatic Lesions.
AB  - OBJECTIVE: The purpose of the study was to determine the role of computed
      tomography (CT) perfusion in differentiating hemangiomas from malignant hepatic
      lesions. MATERIALS AND METHODS: This study was approved by the institutional
      review board. All the patients provided informed consent. CT perfusion was
      performed with 64 multidetector CT (MDCT) scanner on 45 patients including 27
      cases of metastasis, 9 cases of hepatocellular carcinoma (HCC), and 9 cases of
      hemangiomas. A 14 cm span of the liver was covered during the perfusion study.
      Data was analyzed to calculate blood flow (BF), blood volume (BV), permeability
      surface area product (PS), mean transit time (MTT), hepatic arterial fraction
      (HAF), and induced residue fraction time of onset (IRFTO). CT perfusion
      parameters at the periphery of lesions and background liver parenchyma were
      compared. RESULTS: Significant changes were observed in the perfusion parameters
      at the periphery of different lesions. Of all the perfusion parameters BF, HAF,
      and IRFTO showed most significant changes. In our study we found: BF of more than
      400 ml/100 g/min at the periphery of the hemangiomas showed sensitivity of 88.9%,
      specificity of 83.3%, positive predictive value (PPV) of 57.1%, and negative
      predictive value (NPV) of 96.7% in differentiating hemangiomas from hepatic
      malignancy; HAF of more than 60% at the periphery of hemangiomas showed
      sensitivity of 77.8%, specificity of 86.1%, PPV of 58.3% and NPV of 93.9% in
      differentiating hemangiomas from hepatic malignancy; IRFTO of more than 3 s at
      the periphery of hemangiomas showed sensitivity of 77.8%, specificity of 86.1%,
      PPV of 58.3%, and NPV of 93.9% in differentiating hemangiomas from hepatic
      malignancy. CONCLUSION: Perfusion CT is a helpful tool in differentiating
      hemangiomas from hepatic malignancy by its ability to determine changes in
      perfusion parameters of the lesions.

PMID- 24744968
TI  - Endovascular coil occlusion of traumatic intradural aneurysm with presentation as
      carotid cavernous fistula.
AB  - Carotid cavernous fistulae (CCF) are abnormal communication between cavernous
      segment of the internal carotid artery and cavernous sinus. These entities are
      usually encountered in 0.2-0.8% of patients with traumatic skull base fractures.
      Traumatic cerebral aneurysms are rare and account for less than 1% of
      intracranial aneurysms. CCF due to ruptured intradural traumatic aneurysm is very
      rare and difficult to treat by surgical methods. We present one such case of a 40
      year-old man with post-traumatic CCF due to a ruptured intradural aneurysm
      successfully treated with endovascular embolization. 

PMID- 24744970
TI  - Momentum continues.

PMID- 24744969
TI  - Ultrasound and Doppler US in Evaluation of Superficial Soft-tissue Lesions.
AB  - Improved developments in digital ultrasound technology and the use of high
      frequency broadband transducers make ultrasound (US) imaging the first screening
      tool in investigating superficial tissue lesions. US is a safe (no ionizing
      radiation), portable, easily repeatable, and cheap form of imaging compared to
      other imaging modalities. US is an excellent imaging modality to determine the
      nature of a mass lesion (cystic or solid) and its anatomic relation to adjoining
      structures. Masses can be characterized in terms of their size, number,
      component, and vascularity with US and Doppler US especially with power Doppler
      US. US, however, is operator dependent and has a number of artifacts that can
      result in misinterpretation. In this review, we emphasize the role of ultrasound,
      particularly power Doppler, in superficial soft-tissue lesions. 

PMID- 24744971
TI  - Sonography in the diagnosis and assessment of dengue Fever.
AB  - OBJECTIVE: The objective of the following study is to determine the use of
      ultrasound as an important adjunct to clinical and laboratory profile in
      diagnosing dengue fever and in predicting the severity of the disease by
      correlating imaging features with platelet count. The variation in sonographic
      features seen in patients from different age groups was also studied. MATERIALS
      AND METHODS: This is a retrospective study. 96 patients who were serologically
      diagnosed as having dengue fever between April and August 2012 were referred for
      ultrasound scanning of the abdomen and thorax and the imaging findings were
      analyzed. RESULTS: Out of 96 sero-positive dengue cases, 64 (66.7%) patients
      showed edematous gallbladder (GB) wall thickening, 62 (64.5%) patients showed
      ascites, 48 (50%) patients had pleural effusion, 17 (17.7%) patients had
      hepatomegaly, 16 (16.7%) patients had splenomegaly and in 17 (17.7%) patients
      ultrasound findings were normal. Edematous GB wall thickening, ascites and
      pleural effusion were the most common combination of findings in all age groups.
      Edematous GB wall thickening was seen in 97.8% of patients with platelet count of
      less than 40,000 along with ascites (86.9%) and pleural effusion (58.6%). In
      patients with platelet count between 40,000 and 80,000 ascites was more common
      than edematous GB wall thickening. Significantly no abnormal sonographic finding
      was detected in patient with platelet count more than 150,000. CONCLUSION:
      Sonographic features of thickened GB wall, pleural effusion (bilateral or right
      side), ascites, hepatomegaly and splenomegaly should strongly favor the diagnosis
      of dengue fever in patients presenting with fever and associated symptoms,
      particularly during an epidemic. The degree of thrombocytopenia showed a
      significant direct relationship to abnormal ultrasound features.

PMID- 24744972
TI  - A rare case of oropharyngeal teratoma diagnosed antenatally with MRI.
AB  - Oropharyngeal teratomas are extremely rare congenital tumors and have an
      incidence rate of one in 35,000-200,000 newborn babies/neonates. Oropharyngeal
      teratomas may cause life threatening airway obstruction to a newborn. Early
      diagnosis with ultrasound and magnetic resonance imaging (MRI) is essential to
      plan management. Here, we present a rare case of oropharyngeal true teratoma
      diagnosed with MRI antenatally in a fetus at 34 weeks of gestation in a 25-year
      old female who was being evaluated for polyhydraminos. We found MRI to be more
      helpful for antenatal diagnosis, counseling, and management than ultrasonography
      and computed tomography (CT). 

PMID- 24744973
TI  - Difficulty in Clinical Evaluation of Radial Nerve Injury due to Multiple Trauma
      to the Humerus, Wrist, and Hand.
AB  - Radial nerve damage is frequently encountered in humeral fractures. The radial
      nerve is primarily damaged when the humerus gets fractured, while secondary
      damage maybe due to post-traumatic manipulations and surgical exploration. High
      impact traumatic nerve injury, serious neuropathic pain, lack of response to
      therapeutic interventions, and indifference to the Tinel test are indications for
      surgical intervention. Since most humeral fracture-induced low impact radial
      nerve injuries resolve spontaneously, conservative therapy is preferred. We
      present a patient with humeral fracture-associated radial nerve injury,
      accompanied with digital amputation and flexor tendon avulsion on the same arm.
      These injuries required immediate surgery, thus rendering the clinical evaluation
      of the radial nerve impossible. We would like to highlight and discuss the
      inherent difficulties associated with multiple trauma of the upper arm. 

PMID- 24744974
TI  - Establishing a chest MRI practice and its clinical applications: our insight and
      protocols.
AB  - Despite its nonionizing technique and exquisite soft tissue characterization,
      noncardiovascular, and nonmusculoskeletal magnetic resonance imaging (MRI) of the
      chest has been considered impractical due to various challenges such as
      respiratory motion, cardiac motion, vascular pulsatility, air susceptibility, and
      paucity of signal in the lung. With advances in MRI, it is now possible to
      perform diagnostically useful and good quality MRIs of the chest, but literature
      on subspecialized chest MRI practices is limited. The purpose of this manuscript
      is to describe the rationale, nuances, and logistics that went into developing
      such a practice in the Division of Thoracic Radiology at our institution. The
      topics addressed include technical and clinical considerations, support at
      administrative and clinical levels, protocol development, and economic
      considerations compared with conventional practices. Various MRI techniques are
      also specifically discussed to facilitate chest MRI at other sites. Although
      chest MRI is used in a relatively small number of patients at this point, in
      certain patients, chest MRI can provide additional information to optimize
      medical management. A few clinical cases illustrate the quality and clinical
      utility of chest MRI. Given recent advances in MRI techniques, it is now an
      opportune time to develop a chest MRI practice. 

PMID- 24744975
TI  - Substantial Morbidity and Mortality Associated with Pandemic A/H1N1 Influenza in
      Mexico, Winter 2013-2014: Gradual Age Shift and Severity.
AB  - BACKGROUND: A recrudescent wave of pandemic influenza A/H1N1 is underway in
      Mexico in winter 2013-14, following a mild 2012-13 A/H3N2 influenza season.
      Mexico previously experienced several waves of pandemic A/H1N1 activity in
      spring, summer and fall 2009 and winter 2011-2012, with a gradual shift of
      influenza-related hospitalizations and deaths towards older ages. Here we
      describe changes in the epidemiology of the 2013-14 A/H1N1 influenza outbreak,
      relative to previous seasons dominated by the A/H1N1 pandemic virus. The analysis
      is intended to guide public health intervention strategies in near real time.
      METHODS: We analyzed demographic and geographic data on hospitalizations with
      severe acute respiratory infection (SARI), laboratory-confirmed A/H1N1 influenza
      hospitalizations, and inpatient deaths, from a large prospective surveillance
      system maintained by the Mexican Social Security medical system during 01-October
      2013 to 31-Jan 2014. We characterized the age and regional patterns of influenza
      activity relative to the preceding 2011-2012 A/H1N1 influenza epidemic. We also
      estimated the reproduction number (R) based on the growth rate of daily case
      incidence by date of symptoms onset. RESULTS: A total of 7,886 SARI
      hospitalizations and 529 inpatient-deaths (3.2%) were reported between 01-October
      2013 and 31-January 2014 (resulting in 3.2 laboratory-confirmed A/H1N1
      hospitalizations per 100,00 and 0.52 laboratory-confirmed A/H1N1-positive deaths
      per 100,000). The progression of daily SARI hospitalizations in 2013-14 exceeded
      that observed during the 2011-2012 A/H1N1 epidemic. The mean age of laboratory
      confirmed A/H1N1 patients in 2013-14 was 41.1 y (SD=20.3) for hospitalizations
      and 49.2 y (SD=16.7) for deaths. Rates of laboratory-confirmed A/H1N1
      hospitalizations and deaths were significantly higher among individuals aged 30
      59 y and lower among younger age groups for the ongoing 2013-2014 epidemic,
      compared to the 2011-12 A/H1N1 epidemic (Chi-square test, P<0.001). The
      reproduction number of the winter 2013-14 wave in central Mexico was estimated at
      1.3-1.4 which is slightly higher than that reported for the 2011-2012 A/H1N1
      epidemic. CONCLUSIONS: We have documented a substantial and ongoing increase in
      the number of A/H1N1-related hospitalizations and deaths during the period
      October 2013-January 2014 and a proportionate shift of severe disease to middle
      aged adults, relative to the preceding A/H1N1 2011-2012 epidemic in Mexico. In
      the absence of clear antigenic drift in globally circulating A/H1N1 viruses in
      the post-pandemic period, the gradual change in the age distribution of A/H1N1
      infections observed in Mexico suggests a slow build-up of immunity among younger
      populations, reminiscent of the age profile of past pandemics.

PMID- 24744977
TI  - Hypoxia and tumor-associated macrophages: A deadly alliance in support of tumor
      progression.
AB  - Tumor-associated macrophages (TAMs) provide a significant contribution to tumor
      growth and metastasis. We demonstrated the existence of two main TAM subsets,
      differing in activation state and localization. Of these, M2-like TAMs reside in
      hypoxic regions of the tumor mass and can be used as targets for hypoxia tracers.
      This said, hypoxia does not regulate the differentiation of TAMs but finely tunes
      the activity of the M2-like population.

PMID- 24744976
TI  - Digestion of Protein in Premature and Term Infants.
AB  - Premature birth rates and premature infant morbidity remain discouragingly high.
      Improving nourishment for these infants is the key for accelerating their
      development and decreasing disease risk. Dietary protein is essential for growth
      and development of infants. Studies on protein nourishment for premature infants
      have focused on protein requirements for catch-up growth, nitrogen balance, and
      digestive protease concentrations and activities. However, little is known about
      the processes and products of protein digestion in the premature infant. This
      review briefly summarizes the protein requirements of term and preterm infants,
      and the protein content of milk from women delivering preterm and at term. An in
      depth review is presented of the current knowledge of term and preterm infant
      dietary protein digestion, including human milk protease and anti-protease
      concentrations; neonatal intestinal pH, and enzyme activities and concentrations;
      and protein fermentation by intestinal bacteria. The advantages and disadvantages
      of incomplete protein digestion as well as factors that increase resistance to
      proteolysis of particular proteins are discussed. In order to better understand
      protein digestion in preterm and term infants, future studies should examine
      protein and peptide fragment products of digestion in saliva, gastric, intestinal
      and fecal samples, as well as the effects of the gut micro biome on protein
      degradation. The confluence of new mass spectrometry technology and new
      bioinformatics programs will now allow thorough identification of the array of
      peptides produced in the infant as they are digested.

PMID- 24744978
TI  - AMD3100 protects from UV-induced skin cancer.
AB  - Sunlight causes skin cancer by directly damaging DNA as well as by suppressing
      antitumor immune responses. A major mechanism whereby sunlight exerts
      immunosuppressive effects is by modulating the migration of chemokine (C-X-C
      motif) receptor 4 (CXCR4)-expressing dermal mast cells into and away from the
      skin. We have demonstrated the importance of this by showing that the systemic
      administration of the CXCR4 antagonist AMD3100 prevents sunlight-induced
      immunosuppression as well as the consequent carcinogenic response. Our results
      highlight the therapeutic potential of antagonizing CXCR4 signaling, especially
      in individuals who are at high risk of developing skin cancer.

PMID- 24744979
TI  - Modulating antigen processing for cancer immunotherapy.
AB  - The intracellular aminopeptidases that process antigenic epitopes have been
      recently shown to be valid targets for eliciting cell-mediated antitumor immune
      responses. Here, we discuss the recent development of potent, low molecular
      weight inhibitors of these enzymes and how such compounds may constitute a
      promising tool for cancer immunotherapy.

PMID- 24744980
TI  - Food, pathogen, signal: The multifaceted nature of a bacterial diet.
AB  - C. elegans, both in the wild and in the lab, live on a diet of live bacteria. The
      bacterial diet provides nutrients for C. elegans, but can also play a number of
      other roles in C. elegans physiology. Recently, we compared the effects of
      different bacterial diets on life history traits and gene expression. Here, we
      discuss our recent findings in the context of other dietary studies and highlight
      challenges in understanding dietary effects. For instance, since bacteria can be
      pathogenic it can be difficult to disentangle pathogenic from dietary effects.
      Here we summarize different bacterial diets used for C. elegans and how they
      affect the animal. 

PMID- 24744982
TI  - Functional analysis of the miRNA-mRNA interaction network in C. elegans.
AB  - MicroRNAs (miRNAs) are conserved small non-coding RNAs that typically regulate
      gene expression by binding to the 3' untranslated region (UTR) of mRNAs.
      Developmental functions of miRNAs have been extensively studied, but additional
      roles in various cellular processes remain to be understood. The investigation of
      the biological importance of individual miRNA-target interactions and the miRNA
      target interaction network as a whole has been an exciting and challenging field
      of study. Here we briefly discuss the contributions our lab has made to our
      understanding of the physiological impact of this miRNA-network in C. elegans, in
      the context of recent studies in this advancing field. These studies have
      advanced our knowledge of the role of miRNAs in ensuring a robust cellular
      response to different physiological conditions. We briefly outline the genetic,
      biochemical, and computational strategies utilized to understand miRNA functions
      and discuss our recent study of the miRNA-interaction network in neurons and
      potential directions for future studies. 

PMID- 24744981
TI  - C. elegans RNA-binding protein GLD-1 recognizes its multiple targets using
      sequence, context, and structural information to repress translation.
AB  - Caenorhabditis elegans GLD-1, a maxi-KH motif containing RNA-binding protein, has
      various functions mainly during female germ cell development, suggesting that it
      likely controls the expression of a selective group of maternal mRNAs. To gain an
      insight into how GLD-1 specifically recognizes these mRNA targets, we identified
      38 biochemically proven GLD-1 binding regions from multiple mRNA targets that are
      among over 100 putative targets co-immunoprecipitated with GLD-1. The sequence
      information of these regions revealed three over-represented and phylogenetically
      conserved sequence motifs. We found that two of the motifs, one of which is
      novel, are important for GLD-1 binding in several GLD-1 binding regions but not
      in other regions. Further analyses indicate that the importance of one of the
      sequence motifs is dependent on two aspects: (1) surrounding sequence
      information, likely acting as an accessory feature for GLD-1 to efficiently
      select the sequence motif and (2) RNA secondary structural environment where the
      sequence motif resides, which likely provides "binding-site accessibility" for
      GLD-1 to effectively recognize its targets. Our data suggest some mRNAs recruit
      GLD-1 by a distinct mechanism, which involves more than one sequence motif that
      needs to be embedded in the correct context and structural environment. 

PMID- 24744983
TI  - O-GlcNAc cycling shows neuroprotective potential in C. elegans models of
      neurodegenerative disease.
AB  - C. elegans has proven to be an excellent organism in which to model human
      neurodegenerative disease.(1) (-) (7) The worm's simple nervous system, lineage,
      and neural maps, easily scored movement phenotypes, and robust forward and
      reverse genetics make it optimal for studying age-dependent processes on a
      reasonable time scale. A popular approach has been the introduction of transgenes
      expressing GFP-tagged proteotoxic human proteins into neurons leading to visible
      aggregation or movement phenotypes.(2) (,) (4) (,) (6) (,) (8) (-) (13) In
      addition, the maintenance of proteostasis networks has been extensively studied
      using the power of worm genetics.(8) (-) (13) These networks include genes
      involved in insulin-like signaling, the heat shock response, the response to
      hypoxia, and mTOR and AMPK pathways linked to aging.(14) Another pathway with
      suggestive links to neurodegeneration is the O-GlcNAc cycling pathway, a nutrient
      dependent post-translational modification known to be altered in brains from
      patients with Alzheimer disease.(15) (-) (19) In this commentary, we summarize
      our recent findings showing that viable mutants of O-GlcNAc cycling in C. elegans
      dramatically alter the neurotoxicity of four distinct C. elegans models of
      neurodegenerative disease.(7) Mutants in O-GlcNAc cycling alter the toxicity of
      mutant tau, polyglutamine expansion reporters, and amyloid beta-peptide. The
      findings further suggest that O-GlcNAc cycling acts at many steps in the
      lifecycle of aggregation-prone targets. The C. elegans system is likely to
      continue to provide insights into this complex problem. The involvement of O
      GlcNAc cycling in the maintenance of proteostasis raises the possibility of
      targeting the enzymes catalyzing this critical post-translational modification
      for therapeutic intervention. 

PMID- 24744984
TI  - PAQR-2 may be a regulator of membrane fluidity during cold adaptation.
AB  - PAQR-2 is a C. elegans homolog of the mammalian adiponectin receptors. We have
      recently shown that PAQR-2 is essential for the ability of C. elegans to grow at
      its lower temperature range, i.e., 15  degrees C, and that the likely role of
      PAQR-2 during cold adaptation is to regulate membrane fluidity by promoting fatty
      acid desaturation. Here we present a summary of this work, with an emphasis on
      placing our C. elegans findings in the context of mammalian biology. 

PMID- 24744985
TI  - Neuronal cell fate decisions:  O2 and CO2 sensing neurons require egl-13/Sox5.
AB  - We recently conducted a study that aimed to describe the differentiation
      mechanisms used to generate O2 and CO2 sensing neurons in C. elegans. We
      identified egl-13/Sox5 to be required for the differentiation of both O2 and CO2
      sensing neurons. We found that egl-13 functions cell autonomously to drive O2 and
      CO2 sensing neuron fate and is therefore essential for O2 and CO2 sensing-induced
      behaviors. Through systematic dissection of the egl-13 promoter we identified
      upstream regulators of egl-13 and proposed a model of how differentiation of O2
      and CO2 sensing neurons is regulated. In this commentary we discuss our findings
      and open questions we wish to address in future studies. 

PMID- 24744986
TI  - How and why Caenorhabditis elegans uses distinct escape and avoidance regimes to
      minimize exposure to noxious heat.
AB  - Minimizing the exposure to deleterious extremes of temperature is essential for
      animals to avoid tissue damages. Because their body temperature equilibrates very
      rapidly with their surroundings, small invertebrates are particularly vulnerable
      to the deleterious impact of high temperatures, which jeopardizes their growth,
      fertility, and survival. The present article reviews recent analyses of
      Caenorhabditis elegans behavior in temperature gradients covering innocuous and
      noxious temperatures. These analyses have highlighted that worm uses two
      separate, multi-componential navigational strategies: an avoidance strategy,
      aiming at staying away from noxious heat, and an escape strategy, aiming at
      running away after exposure. Here, I explain why efficient escape and avoidance
      mechanisms are mutually exclusive and why worm needs to switch between distinct
      behavioral regimes to achieve efficient protective thermoregulation.
      Collectively, these findings reveal some largely unrecognized strategies
      improving worm goal-directed navigation and the fascinating level of
      sophistication of the behavioral responses deployed to minimize the exposure to
      noxious heat. Because switching between avoidance and escape regimes circumvents
      constraints that are valid for navigation behaviors in general, similar solutions
      might be used by worms and also other organisms in response to various
      environmental parameters covering an innocuous/noxious, non-toxic/toxic range. 

PMID- 24744987
TI  - Active transcriptomic and proteomic reprogramming in the C. elegans nucleotide
      excision repair mutant xpa-1.
AB  - Oxidative stress promotes human aging and contributes to common neurodegenerative
      diseases. Endogenous DNA damage induced by oxidative stress is believed to be an
      important promoter of neurodegenerative diseases. Although a large amount of
      evidence correlates a reduced DNA repair capacity with aging and
      neurodegenerative disease, there is little direct evidence of causality.
      Moreover, the contribution of oxidative DNA damage to the aging process is poorly
      understood. We have used the nematode Caenorhabditis elegans to study the
      contribution of oxidative DNA damage and repair to aging. C. elegans is
      particularly well suited to tackle this problem because it has a minimum
      complexity DNA repair system, which enables us to circumvent the important
      limitation presented by the extensive redundancy of DNA repair enzymes in
      mammals. 

PMID- 24744988
TI  - Will the Requirement by the US FDA to Simultaneously Co-Develop Companion
      Diagnostics (CDx) Delay the Approval of Receptor Tyrosine Kinase Inhibitors for
      RTK-Rearranged (ROS1-, RET-, AXL-, PDGFR-alpha-, NTRK1-) Non-Small Cell Lung
      Cancer Globally?
AB  - The discovery of anaplastic lymphoma kinase (ALK) rearrangement in non-small cell
      lung cancer (NSCLC) in 2007 and the approval of crizotinib for the treatment of
      advanced ALK-rearranged NSCLC in 2011 represents a landmark in the development of
      targeted oncology therapy. The approval of crizotinib was accompanied
      simultaneously by the approval of the Vysis (Abbott Molecular) break-apart
      fluorescence in situ hybridization (FISH) test as the companion diagnostic (CDx)
      test to detect ALK rearrangement. Pfizer, the manufacturer of crizotinib,
      sponsored the screening of thousands of patients and the standardization of the
      ALK FISH test as part of the approval process for crizotinib, a first in class
      ALK inhibitor. Many pharmaceutical companies are now using the Food and Drug
      Administration (FDA)-approved ALK FISH assay to enroll patients onto trials for
      their own respective ALK inhibitors. In essence they are "piggybacking" on the
      FDA-approved ALK FISH assay without having to pay for the development of a CDx,
      nor screening for ALK-rearranged NSCLC patients in the protocols because
      screening for ALK rearrangement is now the standard of care in NSCLC after the
      approval of crizotinib. Since 2007, rearrangement in more receptor tyrosine
      kinases (RTKs) such as ROS1, RET, AXL, PDGFR-alpha, and NTRK1 have been
      discovered in NSCLC but the incidence of each subtype of RTK-rearranged NSCLC is
      quite rare. Crizotinib has now demonstrated significant clinical activity in ROS1
      rearranged NSCLC patients. Whether crizotinib will gain official FDA approval for
      use in ROS1-rearranged NSCLC, on the other hand, remains unclear as there is no
      test for ROS1-rearrangement currently being developed to support US FDA approval
      as a CDx. This may be due in part to the fact that the full cost associated with
      the development of a pre-market approved-approved CDx must be borne by the
      company seeking the first drug approval in a new indication. Given the low
      incidence of ROS1-rearrangement in NSCLC, and the availability of crizotinib in
      most countries, a more cost-effective way is for crizotinib to gain compendium
      listing for ROS1-rearranged NSCLC in treatment guidelines. However, without a
      formal indication from the FDA, a drug cannot be marketed for off label use, it
      is unlikely that payers public or private will routinely pay for molecular
      testing for ROS1-rearrangement in NSCLC let alone reimburse off label use of
      crizotinib. Similarly, several marketed tyrosine kinase inhibitors (TKIs) in the
      US (sorafenib, sunitinib, vandetanib, cabozantinib, regorafenib) are potent RET
      inhibitors in vitro. It does not make sense for any one pharmaceutical company to
      shoulder the full cost of developing a particular CDx for RET-rearranged NSCLC
      where, once approved, it may be used by other pharmaceutical companies to gain
      addition labeling approval for their own RET inhibitors. Thus, the requirement by
      the US FDA that a specific CDx have to be co-developed and standardized for each
      of the molecular subtype of NSCLC as part of the drug approval process, while
      prudent, may have the un-intended consequence of deterring clinical development
      of these TKIs in these very rare molecular subsets of NSCLC. While we all march
      to the drumbeat of precision cancer medicine, the stringent requirement of co
      development CDx for each molecular subtype of solid tumor may inadvertently make
      this goal substantially more difficult to achieve. 

PMID- 24744989
TI  - Blinatumomab, a Bi-Specific Anti-CD19/CD3 BiTE((r)) Antibody for the Treatment of
      Acute Lymphoblastic Leukemia: Perspectives and Current Pediatric Applications.
AB  - Leukemia is the most common childhood malignancy and acute lymphoblastic leukemia
      (ALL) represents the largest sub-type. Despite remarkable improvements over the
      last 40 years, standard therapy fails in 10-20% of newly diagnosed patients.
      Survival for children with relapsed ALL is poor, and the development and
      implementation of novel therapeutic strategies in pediatric ALL are critical to
      further advancements. Immunotherapeutic approaches have been central to more
      novel ALL therapies. However, more recent innovation in antibody engineering has
      improved potency and efficacy, and antibody-drug conjugates (ADCs) are an
      especially attractive option in severely immunocompromised patients. An even more
      sophisticated antibody design is that of bi-specific T-cell engaging or BiTE((r))
      antibodies, which directly recruit effector T cells to augment the anti
      neoplastic effect. This review focuses on blinatumomab, a bi-specific anti
      CD19/CD3 antibody that has shown efficacy in adult patients with precursor B-ALL
      and is currently being evaluated in the pediatric setting. 

PMID- 24744990
TI  - HPV Infection in Cervical and Other Cancers in Saudi Arabia: Implication for
      Prevention and Vaccination.
AB  - Human papillomavirus (HPV) is closely associated with cervical cancer that the
      incidence of this tumor is regarded as a surrogate marker for HPV infection in
      countries lacking epidemiological studies. HPV is also implicated in subsets of
      anogenital and oropharyngeal cancers. Although cervical cancer is the third most
      common cancer in women worldwide, its reported incidence is low in Saudi Arabia,
      ranking number 12 between all cancers in females and accounts only for 2.4% of
      all new cases, despite the lack of national screening programs. However, the
      limited available studies from Saudi Arabia indicate that HPV prevalence and
      genotypes' distribution in invasive cervical cancer show similar pattern as in
      the world. Cytology screening (Pap smear) and HPV vaccinations are the two
      preventive measures against cervical cancer. The two available vaccines are
      effective against the two most common HPV genotypes (HPV-16 and -18). Since 92%
      of cervical tumors in the Kingdom are infected with HPV of which 78% are HPV-16
      and -18 genotypes, vaccination is expected to protect against more than two-third
      of cervical cancers in Saudi Arabia. Nevertheless, due to its low incidence
      (2.1/100,000 women), a proper cost-effectiveness analysis is required to justify
      the implementation of a costly vaccine bearing in mind that HPV could potentially
      be associated with about 3% of all cancers. However, further studies are needed
      to ascertain the real prevalence of HPV at the population level at large, its
      association with various types of cancers, and also the impact of local tradition
      and emerging behavioral trends that could affect HPV transmission and
      consequently the effectiveness of applying national vaccination program. 

PMID- 24744991
TI  - Impacts of endogenous retroviruses on tumorigenesis, immunity, stem cells, and
      research safety.

PMID- 24744992
TI  - Phase II Trial of Erlotinib during and after Radiotherapy in Children with Newly
      Diagnosed High-Grade Gliomas.
AB  - BACKGROUND: Epidermal growth factor receptor is overexpressed in most pediatric
      high-grade gliomas (HGG). Since erlotinib had shown activity in adults with HGG,
      we conducted a phase II trial of erlotinib and local radiotherapy (RT) in
      children with newly diagnosed HGG. METHODS: Following maximum surgical resection,
      patients between 3 and 21 years with non-metastatic HGG received local RT at 59.4
      Gy (54 Gy for spinal tumors and those with >=70% brain involvement). Erlotinib
      started on day 1 of RT (120 mg/m(2) per day) and continued for 2 years unless
      there was tumor progression or intolerable toxicities. The 2-year progression
      free survival (PFS) was estimated for patients with intracranial anaplastic
      astrocytoma (AA) and glioblastoma (GBM). RESULTS: Median age at diagnosis for 41
      patients with intracranial tumors (21 with GBM and 20 with AA) was 10.9 years
      (range, 3.3-19 years). The 2-year PFS for patients with AA and GBM was 15 +/- 7
      and 19 +/- 8%, respectively. Only five patients remained alive without tumor
      progression. Twenty-six patients had at least one grade 3 or 4 toxicity
      irrespective of association with erlotinib; only four required dose
      modifications. The main toxicities were gastrointestinal (n = 11), dermatologic
      (n = 5), and metabolic (n = 4). One patient with gliomatosis cerebri who required
      prolonged corticosteroids died of septic shock associated with pancreatitis.
      CONCLUSION: Although therapy with erlotinib was mostly well-tolerated, it did not
      change the poor outcome of our patients. Our results showed that erlotinib is not
      a promising medication in the treatment of children with intracranial AA and GBM.

PMID- 24744993
TI  - Study of the knowledge of pediatricians and senior residents relating to the
      importance of hearing impairment and deafness screening among newborns.
AB  - INTRODUCTION: Newborn hearing screening leads to the early detection of hearing
      impairment. The aim of screening is to decrease or remove the effect of hearing
      impairment on development of speech and language by timely diagnosis and
      effective treatment. A number of risk factors lead to delayed start of decreased
      hearing ability including: 1. Congenital infection with cytomegalovirus (CMV)
      virus, 2. Meningitis, 3. Mumps, 4. Positive family history, 5. Head trauma, 6.
      Chemotherapy,7. Syndrome pertaining to delayed start of decreased hearing.
      Unfortunately, lack of attention to early diagnosis of hearing impairment is
      becoming a general health problem. No research has yet been carried out relating
      to the knowledge of pediatricians on this issue, particularly the importance of
      hearing impairment and hearing screening. The aim of this study was to determine
      the attitude to newborn hearing screening among pediatricians. MATERIALS AND
      METHODS: This cross-sectional, descriptive-analytic study was conducted in
      Isfahan in 2012 among 300 pediatricians and final-year pediatric residents. An
      adjusted 22-question version of the Early Hearing Detection and Intervention
      (EHDI) questionnaire was used to collect data. The validity and reliability of
      the EHDI questionnaire was previously demonstrated by Boys Town National Research
      Hospital and its Farsi translated version was validated by the EDC Center at the
      Isfahan University of Medical Sciences. RESULTS: In our study, 83% of
      pediatricians agreed on the importance of hearing impairment screening for all
      infants. However 65% were not aware of special needs for hearing-impaired
      patients. CONCLUSION: Newborn hearing impairment and deafness screening is
      important, irrespective of the costs, and lack of timely diagnosis results in
      both individual and social consequences. The majority of physicians use textbooks
      to gain information about hearing screening, but recognize that this is
      insufficient. Although it is now one of the most useful tools for gathering and
      applying new information, the physicians in our study rely very little on the
      Internet as a source of information.

PMID- 24744994
TI  - Comparison of the Speech Syntactic Features between Hearing-Impaired and Normal
      Hearing Children.
AB  - INTRODUCTION: The present study seeks to describe and analyze the syntactic
      features of children with severely hearing loss who had access to the hearing
      aids compared with children with normal hearing, assigning them to the same
      separate gender classes. MATERIALS AND METHODS: In the present study, eight
      children with severe hearing impairment who used a hearing aid and eight hearing
      children matched for age and gender were selected using an available sampling
      method based on the principles of auditory-verbal approach. Hearing children had
      an average age of 5.45 +/-1.9 years and subjects had a mean age of 5.43+/-2.17
      years and their rehabilitation had begun before they were 18 months old. The
      assessment instrument of the study included the language development test, TOLDP
      3. The syntactic skills of these children were analyzed and compared with the
      hearing children of the same age based on gender. RESULTS: There was a
      significant difference between the syntactic scores of the hearing-impaired
      children and the scores of the hearing children of the same age in the "sentence
      imitation" (t=-2/90, P<0/05) and "grammatical completion" (t=-3/39, P<0/05)
      subtests, with no significant difference in the "grammatical understanding"
      subtest (t=1/67, P>0/05). Moreover, there was no significant difference between
      male and female children with hearing impairment in terms of syntactic skills
      development. CONCLUSION: With early diagnosis and timely rehabilitating
      intervention, children with hearing loss can perform in a similar way to children
      of their age with normal hearing in some syntactical areas. Furthermore, the
      gender factor in the present study had no effect on the development of
      syntactical skills of children with hearing loss.

PMID- 24744995
TI  - Alveolar Antral Artery: Review of Surgical Techniques Involving this Anatomic
      Structure.
AB  - INTRODUCTION: The horizontal bony canal in the lateral maxillary wall is the site
      of anastomosis between the arterial branches from the posterior superior alveolar
      artery (PSAa) and the infraorbital artery. This anatomic structure is known as
      the 'alveolar antral artery'. MATERIALS AND METHODS: We performed a literature
      review. The anatomic location of the alveolar antral artery in the lateral
      maxillary sinus wall was researched and its importance in surgical procedures
      routinely performed on this bony wall discussed. RESULTS: This artery can be
      accidentally involved during surgical procedures on the lateral maxillary sinus
      wall, such as open sinus lift surgery, horizontal osteotomy of the maxilla, Le
      Fort I fracture treatment, and Caldwell-Luc surgeries. CONCLUSION: The alveolar
      antral artery is an important anatomic structure in the lateral maxillary sinus
      wall. A preoperative cone beam computed tomography (CBCT) scan can be used as a
      good diagnostic procedure to reduce surgical complications in suspected cases as
      well as conditions that may involve this artery.

PMID- 24744996
TI  - Translation, validity, and reliability of a persian version of the iowa tinnitus
      handicap questionnaire.
AB  - INTRODUCTION: Tinnitus is a common otologic symptom that can seriously affect a
      patient's quality of life. The purpose of the present study was to translate and
      validate the Iowa Tinnitus Handicap Questionnaire (THQ) into the Persian
      language, and to make it applicable as a tool for determining the effects of
      tinnitus on a patient's life. MATERIALS AND METHODS: The main version of the THQ
      was translated into the Persian language. The agreed Persian version was
      administered to 150 tinnitus patients. The validity of the Persian THQ was
      evaluated and internal reliability was confirmed using Cronbach's alpha
      coefficient. Finally, the effect of independent variables such as age, mean
      patient threshold, gender, and duration of tinnitus were considered in order to
      determine the psychometric properties of tinnitus. RESULTS: After an exact
      translation process, the Persian THQ was found to exhibit face validity. In terms
      of content validity, content validity index in total questionnaire was 0.93.
      Further, in structural validity measurements, intermediate correlation with
      annoyance from tinnitus (r=0.49), low correlation with duration of tinnitus
      (r=0.34) and high correlation with the Tinnitus Handicap Inventory (THI)
      questionnaire (r=0.84) were demonstrated. Additionally, a negligible effect of
      gender and age was noted on degree of tinnitus handicap (P= 0.754, P= 0.573,
      respectively). In the internal reliability assessment for Factors 1, 2, 3, and
      the whole questionnaire, Cronbach's alpha-coefficient was 0.95, 0.92, 0.25 and
      0.88, respectively. CONCLUSION: The Persian version of the Iowa THQ demonstrates
      high validity and reliability and can be used for the determination of tinnitus
      handicap and for following-up in the intervention process in Persian tinnitus
      patients.

PMID- 24744997
TI  - Comparing the Effect of Dexamethasone before and after Tracheal Intubation on
      Sore Throat after Tympanoplasty Surgery: A Randomized Controlled trial.
AB  - INTRODUCTION: Presence of a sore throat after surgery is a common side effect of
      general anesthesia with intratracheal intubation and can cause discomfort for the
      patient and prolong the recovery process. In this study we compared the effect of
      dexamethasone before and after intubation on the incidence of sore throat after
      tympanoplasty surgery. MATERIALS AND METHODS: In a double-blind, randomized
      clinical trial, 70 patients aged 30-60 years with American Society of
      Anesthesiologists (ASA) physical status I or II who were candidates for
      tympanoplasty under anesthetic conditions were studied in two separate groups.
      The first group received intravenous (IV) dexamethasone (8 mg) 30 mins prior to
      intubation while the second group received the same dose of dexamethasone 30 mins
      after intubation. The incidence and severity of the sore throat in both groups
      were then evaluated. RESULTS: There was no significant difference between two
      groups in intensity of sore throat (62.9% vs. 57.1%), cough (65.7% vs. 62.9%), or
      hoarseness (62.9% vs. 65.7%) within 24 h after surgery. Detection of blood in
      oral secretions or on the tracheal tube was the same in both groups (5.7%). The
      incidence of coughs during the extubation was 0% in first group and 11.4% in
      second group. CONCLUSION: According to the results of this research there was no
      significant difference in incidence and intensity of sore throat in patients
      receiving dexamethasone before or after intubation. Further, no significant
      difference in intensity of coughs or hoarseness was observed.

PMID- 24744998
TI  - HIV: An Epidemiologic study on Head and Neck Involvement in 50 Patients.
AB  - INTRODUCTION: Acquired immunodeficiency syndrome (AIDS) is a worldwide infection.
      Because of the vast array of manifestations of AIDS and its many atypical
      presentations, it is becoming increasingly challenging for clinicians to
      accurately diagnose new lesions. MATERIALS AND METHODS: In a descriptive cross
      sectional study conducted from 2007 to 2010, 50 patients with a proven human
      immunodeficiency virus (HIV) infection were evaluated. Based on the findings of a
      physical examination and paraclinic tests, HIV signs and symptoms were recorded.
      RESULTS: The mean (range) age of the patients was 35.45 +/-5.24 (5-55) years.
      Forty-two (84%) cases were male and eight were female. The mean duration of
      carrying the virus was 4.51 +/-1.03 years. Oral manifestations were the most
      common (94%), followed by rhinologic (88%), otologic (66%), and finally neck
      (44%) manifestations. CONCLUSION: Head and neck presentations are very common in
      HIV patients; therefore otolaryngologists, as the first physicians who may
      encounter such patients, should be aware of this condition.

PMID- 24744999
TI  - Acoustic sensitivity of the saccule and daf music.
AB  - INTRODUCTION: The daf is a large Persian frame drum used as a musical instrument
      in both popular and classical music which can induce a percussive sound at low
      frequencies (146-290 Hz) with peaks of up to 130 dBspl. The percussive sounds
      have a power distribution in the region of saccular sensitivity. In view of the
      saccular stimulation by sound in humans, we decided to use cervical vestibular
      evoked myogenic potentials (cVEMPs) to evaluate the possibility that the daf
      music may have a disturbing effect on saccular function. MATERIALS AND METHODS:
      During this case-control study, 18 daf musicians were compared with 20 healthy
      individuals evaluated in the audiology department of the Hamadan University of
      Medical Sciences. Assessment consisted of pure tone audiometry, tympanometry, and
      cVEMPs. RESULTS: Multiple comparisons of mean the cVEMPs and mean hearing loss at
      250 Hz among the three groups (affected, unaffected, and normal ears) were
      significant. There were no significant differences between all daf players on
      high-tone loss at 3000 Hz. The daf musicians had bilateral unsymmetrical
      sensorineural hearing loss (SNHL), with hearing loss at 250 Hz (low-tone loss)
      and notched audiogram at 3000 Hz (high-tone loss). Eleven musicians with
      decreased vestibular excitability as detected by abnormal cVEMPs had mild (26-40
      dBHL) low-tone loss and significant abnormal cVEMPs findings. In contrast, the
      others had slight (16-25 dBHL) low-tone loss with normal cVEMPs. Exposure to daf
      music is related to both saccular and cochlear dysfunction. CONCLUSION: Exposure
      to daf music is related to both saccular and cochlear dysfunction.

PMID- 24745000
TI  - A Large Ameloblastic Fibro-odontoma of the Maxillary Sinus.
AB  - INTRODUCTION: Ameloblastic fibro-odontoma is a rare, benign, asymptomatic tumor.
      The term ameloblastic fibro-odontoma was first used by Hooker in 1967 as a
      separate lesion from ameloblastic odontoma. CASE REPORT: This case report
      describes an eleven years old female with large ameloblastic fibro-odontoma in
      the right maxillary sinus. CONCLUSION: There is a low potential for recurrence
      after complete Enucleation of ameloblastic fibro-odontoma, but due to the risk of
      ameloblastic sarcoma after recurrence, the surgery should be perfect along with a
      careful follow up.

PMID- 24745001
TI  - Osteoid osteoma presenting as a painful solitary skull lesion: a case report.
AB  - INTRODUCTION: Osteomas are asymptomatic and rare slow growing bony tumors in
      temporal bone, and should be taken into account in differential diagnosis of the
      osteolytic solitary skull lesions. Sometimes is associated with pain and
      functional loss. Only a few cases have been reported. CASE REPORT: We describe a
      case of an osteoid osteoma of the temporal bone (mastoid) in a 31-year-old woman
      presenting as painful solitary tumor of calvarium and its management. The
      resection of whole bony tumor was performed using the retroauricular approach.
      Pathologic evaluation revealed the osteoid osteoma. CONCLUSION: Although osteoid
      osteoma of the temporal bone is rare, it should be taken into account in
      differential diagnosis of the osteolytic skull lesions. Treatment is indicated
      for symptomatic osteomas or cosmetic reasons.

PMID- 24745002
TI  - Differentiation between CSF Otorrhea and Rhinorrhea in an Obscure Case of
      Recurrent Meningitis.
AB  - INTRODUCTION: Leakage of cerebrospinal fluid in the skull base may be accompanied
      with recurrent meningitis. The site of leakage may either be anterior (in the
      nose and paranasal sinuses) or posterior (in the temporal bone). Various imaging
      techniques can be used to precisely locate the point of leakage but despite all
      the advances in imaging techniques there are still some rare cases in which the
      surgeon can't be sure on the management approach before the beginning of surgery.
      CASE REPORT: In this article we present one of these cases; we used intrathecal
      fluorescein to locate the source of the leak and made the final decision on the
      operating table. CONCLUSION: Intrathecal fluorescein is helpful in locating the
      leakage in the ear or the nose in ambiguous cases.

PMID- 24745003
TI  - Mel Avery: Mentor, Role Model, Friend, Mother of Us all.

PMID- 24745004
TI  - The fallacy of chasing after work-life balance.

PMID- 24745006
TI  - The WRKY Transcription Factor Genes in Lotus japonicus.
AB  - WRKY transcription factor genes play critical roles in plant growth and
      development, as well as stress responses. WRKY genes have been examined in
      various higher plants, but they have not been characterized in Lotus japonicus.
      The recent release of the L. japonicus whole genome sequence provides an
      opportunity for a genome wide analysis of WRKY genes in this species. In this
      study, we identified 61 WRKY genes in the L. japonicus genome. Based on the WRKY
      protein structure, L. japonicus WRKY (LjWRKY) genes can be classified into three
      groups (I-III). Investigations of gene copy number and gene clusters indicate
      that only one gene duplication event occurred on chromosome 4 and no clustered
      genes were detected on chromosomes 3 or 6. Researchers previously believed that
      group II and III WRKY domains were derived from the C-terminal WRKY domain of
      group I. Our results suggest that some WRKY genes in group II originated from the
      N-terminal domain of group I WRKY genes. Additional evidence to support this
      hypothesis was obtained by Medicago truncatula WRKY (MtWRKY) protein motif
      analysis. We found that LjWRKY and MtWRKY group III genes are under purifying
      selection, suggesting that WRKY genes will become increasingly structured and
      functionally conserved. 

PMID- 24745005
TI  - MicroRNAs in the Neural Retina.
AB  - The health and function of the visual system rely on a collaborative interaction
      between diverse classes of molecular regulators. One of these classes consists of
      transcription factors, which are known to bind to DNA and control the
      transcription activities of their target genes. For a long time, it was thought
      that the transcription factors were the only regulators of gene expression. More
      recently, however, a novel class of regulators emerged. This class consists of a
      large number of small noncoding endogenous RNAs, namely, miRNAs. The miRNAs
      compose an essential component of posttranscriptional gene regulation, since they
      ultimately control the fate of gene transcripts. The retina, as a part of the
      central nervous system, is a well-established model for unraveling the molecular
      mechanisms underlying neuronal and glial functions. Numerous recent efforts have
      been made towards identification of miRNAs and their inferred roles in the visual
      pathway. In this review, we summarize the current state of our knowledge
      regarding the expression and function of miRNA in the neural retina and we
      discuss their potential uses as biomarkers for some retinal disorders. 

PMID- 24745007
TI  - Identifying potential clinical syndromes of hepatocellular carcinoma using PSO
      based hierarchical feature selection algorithm.
AB  - Hepatocellular carcinoma (HCC) is one of the most common malignant tumors.
      Clinical symptoms attributable to HCC are usually absent, thus often miss the
      best therapeutic opportunities. Traditional Chinese Medicine (TCM) plays an
      active role in diagnosis and treatment of HCC. In this paper, we proposed a
      particle swarm optimization-based hierarchical feature selection (PSOHFS) model
      to infer potential syndromes for diagnosis of HCC. Firstly, the hierarchical
      feature representation is developed by a three-layer tree. The clinical symptoms
      and positive score of patient are leaf nodes and root in the tree, respectively,
      while each syndrome feature on the middle layer is extracted from a group of
      symptoms. Secondly, an improved PSO-based algorithm is applied in a new reduced
      feature space to search an optimal syndrome subset. Based on the result of
      feature selection, the causal relationships of symptoms and syndromes are
      inferred via Bayesian networks. In our experiment, 147 symptoms were aggregated
      into 27 groups and 27 syndrome features were extracted. The proposed approach
      discovered 24 syndromes which obviously improved the diagnosis accuracy. Finally,
      the Bayesian approach was applied to represent the causal relationships both at
      symptom and syndrome levels. The results show that our computational model can
      facilitate the clinical diagnosis of HCC. 

PMID- 24745008
TI  - Comparative evaluation of recombinant protein production in different
      biofactories: the green perspective.
AB  - In recent years, the production of recombinant pharmaceutical proteins in
      heterologous systems has increased significantly. Most applications involve
      complex proteins and glycoproteins that are difficult to produce, thus promoting
      the development and improvement of a wide range of production platforms. No
      individual system is optimal for the production of all recombinant proteins, so
      the diversity of platforms based on plants offers a significant advantage. Here,
      we discuss the production of four recombinant pharmaceutical proteins using
      different platforms, highlighting from these examples the unique advantages of
      plant-based systems over traditional fermenter-based expression platforms. 

PMID- 24745009
TI  - Molecular mechanisms of renal cellular nephrotoxicity due to radiocontrast media.
AB  - Modern iodinated radiocontrast media are all based on the triiodinated benzene
      ring with various chemical modifications having been made over the last few
      decades in order to reduce their toxicity. However, CIN remains a problem
      especially in patients with pre-existing renal failure. In vitro studies have
      demonstrated that all RCM are cytotoxic. RCM administration in vivo may lead to a
      decrease in renal medullary oxygenation leading to the generation of reactive
      oxygen species that may cause harmful effects to renal tissue. In addition,
      endothelin and adenosine release and decreased nitric oxide levels may worsen the
      hypoxic milieu. In vitro cell culture studies together with sparse in vivo rat
      model data have shown that important cell signalling pathways are affected by
      RCM. In particular, the prosurvival and proproliferative kinases Akt and ERK1/2
      have been shown to be dephosphorylated (deactivated), whilst proinflammatory/cell
      death molecules such as the p38 and JNK kinases and the transcription factor NF-
      kappa B may be activated by RCM, accompanied by activation of apoptotic mediators
      such as caspases. Increasing our knowledge of the mechanisms of RCM action may
      help to develop future therapies for CIN. 

PMID- 24745010
TI  - Genetic polymorphisms of ORAI1 and chronic kidney disease in Taiwanese
      population.
AB  - Taiwan has very high incidence and prevalence of chronic kidney disease (CKD),
      which easily progresses to end-stage renal disease (ESRD). The association
      between inflammation and CKD has been explored in several studies. ORAI1
      functions as a pore-forming subunit of the store-operated calcium channels which
      are involved in the regulation of immune system. Hence, we conducted a case
      control study to determine whether the genetic polymorphisms of ORAI1 gene is a
      susceptibility factor to CKD and its clinical features in a Taiwanese population.
      Five hundred seventy-nine CKD patients from a hospital-based CKD care program
      were included in the study. Five tagging single nucleotide polymorphisms (tSNPs)
      of ORAI1 were selected from the genotyping data of the Han Chinese population
      from the HapMap project. Among these polymorphisms, rs12313273 was found to be
      significantly associated with elevated serum calcium levels, which has been
      linked to increased risk of death in CKD patients. To have a better management of
      serum calcium, we suggest that ORAI1 polymorphisms might be used as a potential
      biomarker for initiating non-calcium-based phosphate binder in CKD patients in
      the future. 

PMID- 24745011
TI  - Chemical constituents from the fruits of Forsythia suspensa and their
      antimicrobial activity.
AB  - Lignans and phenylethanoid glycosides purified from Forsythia suspensa were
      reported to display various bioactivities in the previous literature, including
      the antimicrobial activity. Therefore, the present research is aimed to purify
      and identify the chemical constituents of the methanol extracts of fruits of F.
      suspensa. The methanol extracts of fruits of F. suspensa were fractionated and
      further purified with the assistance of column chromatography to afford totally
      thirty-four compounds. Among these isolates, 3 beta -acetoxy-20 alpha 
      hydroxyursan-28-oic acid (1) was reported from the natural sources for the first
      time. Some of the purified principles were subjected to the antimicrobial
      activity examinations against Escherichia coli to explore new natural lead
      compounds. 

PMID- 24745012
TI  - Time-to-delivery after maternal transfer to a tertiary perinatal centre.
AB  - OBJECTIVES: To determine, in women transferred antenatally for acute admission
      with high risk pregnancies, the numbers who deliver, the average time from
      transfer to delivery, and whether the reason for transfer influences the time-to
      delivery. METHODS: A retrospective analysis of time-to-delivery was performed in
      a population of women transferred to the Royal Brisbane and Women's Hospital,
      QLD. Data were obtained from the hospital obstetric, neonatal, and admission
      databases. RESULTS: A total of 941 women were transferred antenatally with high
      risk pregnancies where delivery was deemed potentially imminent. Of these 821
      (87%) delivered at RBWH. The remaining 120 women (13%) were discharged prior to
      delivery and then delivered elsewhere. Of the 821 maternal transfers that
      delivered, the median time to delivery was 24.4 hrs. There were 43% who delivered
      within 24 hours of admission and 29% who either delivered after 7 days or
      delivered elsewhere. Most transfers for fetal abnormality delivered in the first
      24 hours while most transfers for antepartum haemorrhage and preterm prelabour
      membrane rupture delivered beyond 24 hours. CONCLUSION: There are significant
      differences in time-to-delivery following transfer depending on the reason for
      transfer and many infants transferred in utero will not deliver imminently.

PMID- 24745013
TI  - Tension-free vaginal tape, transobturator tape, and own modification of
      transobturator tape in the treatment of female stress urinary incontinence:
      comparative analysis.
AB  - INTRODUCTION: This study is a comparative evaluation of the TVT, TOT, and our own
      modification of TOT (mTOT) in the treatment of female stress urinary incontinence
      from a single center experience. MATERIAL AND METHODS: The study was conducted on
      527 patients with SUI diagnosed on the basis of urodynamic studies. They were
      divided into three groups--TVT: n=142, (TOT): n=129, and mTOT: n=256. All of the
      patients underwent evaluation at 1, 3, and 6 months after surgery. Results were
      statistically analysed and compared. RESULTS: Objective and subjective
      effectiveness after the surgery were not significantly different in the study
      groups and ranged from 90.1% to 96.4%. Mean surgery time was 32.3, 28.2, and 26.4
      in the TVT, TOT, and mTOT, respectively. Mean hospitalization time was 2.51 days.
      Mean catheter maintenance time was significantly higher in the TVT than in other
      groups. In the TVT group total incidence of complications was 13.4%, and it was
      significantly higher than that in TOT and mTOT (9.3% and 8.6%, resp.).
      CONCLUSIONS: TVT, TOT, and mTOT are highly effective and safe methods in the
      treatment of SUI. There are no differences in the efficacy between the methods
      with a little higher percentage of complications in the TVT group.

PMID- 24745014
TI  - EZH2 silencing with RNA interference induces G2/M arrest in human lung cancer
      cells in vitro.
AB  - Nonsmall-cell lung cancer has a high mortality rate and poor prognosis. In the
      present study, we silenced EZH2 and explored the consequent cell cycle changes.
      The expression of cell-cycle-related proteins, including p53, p21, Cdc2, and
      cyclin B1, was detected with western blotting, and the cell cycle distribution
      was determined with flow cytometry. Inhibition of EZH2 expression changed the
      cell cycle distribution, in particular inducing G2/M arrest. Expression of Cdc2
      and cyclin B1 was significantly decreased in A549 and HTB-56 cells after EZH2
      siRNA treatment. In addition, p53 expression was increased by 21% and 18%, and
      p21 expression was increased by 31% and 23%, in A549 and HTB-56 cells,
      respectively, in the presence of EZH2-siRNA. This study clearly demonstrates that
      modulation of EZH2 expression with siRNA affects the cell cycle and the
      expression levels of p53 and p21, thereby changing cyclin B1 and Cdc2 expression
      and inducing G2/M arrest. These results may explain the observed antitumor
      activity of EZH2 silencing. Such explorations of the molecular mechanism of EZH2
      will help us develop novel approaches to the diagnosis, treatment, and prevention
      of nonsmall-cell lung cancer. 

PMID- 24745015
TI  - Functional analyses of C.2268dup in thyroid peroxidase gene associated with
      goitrous congenital hypothyroidism.
AB  - The c.2268dup mutation in thyroid peroxidase (TPO) gene was reported to be a
      founder mutation in Taiwanese patients with dyshormonogenetic congenital
      hypothyroidism (CH). The functional impact of the mutation is not well
      documented. In this study, homozygous c.2268dup mutation was detected in two
      Malaysian-Chinese sisters with goitrous CH. Normal and alternatively spliced TPO
      mRNA transcripts were present in thyroid tissues of the two sisters. The abnormal
      transcript contained 34 nucleotides originating from intron 12. The c.2268dup is
      predicted to generate a premature termination codon (PTC) at position 757
      (p.Glu757X). Instead of restoring the normal reading frame, the alternatively
      spliced transcript has led to another stop codon at position 740
      (p.Asp739ValfsX740). The two PTCs are located at 116 and 201 nucleotides upstream
      of the exons 13/14 junction fulfilling the requirement for a nonsense-mediated
      mRNA decay (NMD). Quantitative RT-PCR revealed an abundance of unidentified
      transcripts believed to be associated with the NMD. TPO enzyme activity was not
      detected in both patients, even though a faint TPO band of about 80 kD was
      present. In conclusion, the c.2268dup mutation leads to the formation of normal
      and alternatively spliced TPO mRNA transcripts with a consequential loss of TPO
      enzymatic activity in Malaysian-Chinese patients with goitrous CH. 

PMID- 24745016
TI  - Association of P2Y12 gene promoter DNA methylation with the risk of clopidogrel
      resistance in coronary artery disease patients.
AB  - BACKGROUND: Clopidogrel inhibits the ADP receptor P2Y12 to keep down the platelet
      aggregation. The goal of our study is to investigate the contribution of P2Y12
      promoter DNA methylation to the risk of clopidogrel resistance (CR). METHODS: The
      platelet functions were measured by the VerifyNow P2Y12 assay. Applying the
      bisulfite pyrosequencing technology, DNA methylation levels of two CpG
      dinucleotides on P2Y12 promoter were tested among 49 CR cases and 57 non-CR
      controls. We also investigated the association among P2Y12 DNA methylation,
      various biochemical characteristics, and CR. RESULT: Lower methylation of two
      CpGs indicated the poorer clopidogrel response (CpG1, P=0.009; CpG2, P=0.022) in
      alcohol abusing status. Meanwhile CpG1 methylation was inversely correlated with
      CR in smoking patients (P=0.026) and in subgroup of Albumin<35 (P=0.002). We
      observed that the level of DNA methylation might be affected by some clinical
      markers, such as TBIL, LEVF, Albumin, AST. The results also showed that the
      quantity of stent, fasting blood-glucose, and lower HbAC1 were the predictors of
      CR. CONCLUSIONS: The evidence from our study indicates that P2Y12 methylation may
      bring new hints to elaborate the pathogenesis of CR.

PMID- 24745017
TI  - Merit of ginseng in the treatment of heart failure in type 1-like diabetic rats.
AB  - The present study investigated the merit of ginseng in the improvement of heart
      failure in diabetic rats and the role of peroxisome proliferator-activated
      receptors delta (PPAR delta ). We used streptozotocin-induced diabetic rat (STZ
      rat) to screen the effects of ginseng on cardiac performance and PPAR delta
      expression. Changes of body weight, water intake, and food intake were compared
      in three groups of age-matched rats; the normal control (Wistar rats) received
      vehicle, STZ-rats received vehicle and ginseng-treated STZ-rats. We also
      determined cardiac performances in addition to blood glucose level in these
      animals. The protein levels of PPAR delta in hearts were identified using Western
      blotting analysis. In STZ-rats, cardiac performances were decreased but the food
      intake, water intake, and blood glucose were higher than the vehicle-treated
      control. After a 7-day treatment of ginseng in STZ-rats, cardiac output was
      markedly enhanced without changes in diabetic parameters. This treatment with
      ginseng also increased the PPAR delta expression in hearts of STZ-rats. The
      related signal of cardiac contractility, troponin I phosphorylation, was also
      raised. Ginseng-induced increasing of cardiac output was reversed by the
      cotreatment with PPAR delta antagonist GSK0660. Thus, we suggest that ginseng
      could improve heart failure through the increased PPAR delta expression in STZ
      rats. 

PMID- 24745018
TI  - Image guided hypofractionated radiotherapy by helical tomotherapy for prostate
      carcinoma: toxicity and impact on Nadir PSA.
AB  - AIM: To evaluate the toxicity of a hypofractionated schedule for primary
      radiotherapy (RT) of prostate cancer as well as the value of the nadir PSA (nPSA)
      and time to nadir PSA (tnPSA) as surrogate efficacy of treatment. MATERIAL AND
      METHODS: Eighty patients underwent hypofractionated schedule by Helical
      Tomotherapy (HT). A dose of 70.2 Gy was administered in 27 daily fractions of 2.6
      Gy. Acute and late toxicities were graded on the RTOG/EORTC scales. The nPSA and
      the tnPSA for patients treated with exclusive RT were compared to an equal cohort
      of 20 patients treated with conventional fractionation and standard conformal
      radiotherapy. RESULTS: Most of patients (83%) did not develop acute
      gastrointestinal (GI) toxicity and 50% did not present genitourinary (GU)
      toxicity. After a median follow-up of 36 months only grade 1 of GU and GI was
      reported in 6 and 3 patients as late toxicity. Average tnPSA was 30 months. The
      median value of nPSA after exclusive RT with HT was 0.28 ng/mL and was
      significantly lower than the median nPSA (0.67 ng/mL) of the conventionally
      treated cohort (P = 0.02). CONCLUSIONS: Hypofractionated RT schedule with HT for
      prostate cancer treatment reports very low toxicity and reaches a low level of
      nPSA that might correlate with good outcomes.

PMID- 24745019
TI  - The role of Hypoxia-inducible factor-1 alpha , glucose transporter-1, (GLUT-1)
      and carbon anhydrase IX in endometrial cancer patients.
AB  - Hypoxia-inducible factor-1alpha (HIF-1alpha), glucose transporter-1 (GLUT-1), and
      carbon anhydrase IX (CAIX) are important molecules that allow adaptation to
      hypoxic environments. The aim of our study was to investigate the correlation
      between HIF-1alpha, GLUT-1, and CAIX protein level with the clinicopathological
      features of endometrial cancer patients. Materials and Methods. 92 endometrial
      cancer patients, aged 37-84, were enrolled to our study. In all patients clinical
      stage, histologic grade, myometrial invasion, lymph node, and distant metastases
      were determined. Moreover, the survival time was assessed. Immunohistochemical
      analyses were performed on archive formalin fixed paraffin embedded tissue
      sections. Results. High significant differences (P = 0.0115) were reported
      between HIF-1alpha expression and the histologic subtype of cancer. Higher HIF
      1alpha expression was associated with the higher risk of recurrence (P = 0.0434).
      The results of GLUT-1 and CAIX expression did not reveal any significant
      differences between the proteins expression in the primary tumor and the
      clinicopathological features. Conclusion. The important role of HIF-1alpha in the
      group of patients with the high risk of recurrence and the negative histologic
      subtype of the tumor suggest that the expression of this factor might be useful
      in the panel of accessory pathomorphological tests and could be helpful in
      establishing more accurate prognosis in endometrial cancer patients. 

PMID- 24745020
TI  - The effectiveness of preemptive thoracic epidural analgesia in thoracic surgery.
AB  - BACKGROUND: The aim of this study is to investigate the effectiveness of
      preemptive thoracic epidural analgesia (TEA) comparing conventional postoperative
      epidural analgesia on thoracotomy. MATERIAL AND METHODS: Forty-four patients were
      randomized in to two groups (preemptive: Group P, control: Group C). Epidural
      catheter was inserted in all patients preoperatively. In Group P, epidural
      analgesic solution was administered as a bolus before the surgical incision and
      was continued until the end of the surgery. Postoperative patient controlled
      epidural analgesia infusion pumps were prepared for all patients. Respiratory
      rates (RR) were recorded. Patient's analgesia was evaluated with visual analog
      scale at rest (VASr) and coughing (VASc). Number of patient's demands from the
      pump, pump's delivery, and additional analgesic requirement were also recorded.
      RESULTS: RR in Group C was higher than in Group P at postoperative 1st and 2nd
      hours. Both VASr and VASc scores in Group P were lower than in Group C at
      postoperative 1st, 2nd, and 4th hours. Patient's demand and pump's delivery count
      for bolus dose in Group P were lower than in Group C in all measurement times.
      Total analgesic requirements on postoperative 1st and 24th hours in Group P were
      lower than in Group C. CONCLUSION: We consider that preemptive TEA may offer
      better analgesia after thoracotomy.

PMID- 24745021
TI  - Red cell distribution width as a prognostic indicator in pediatric heart disease
      and after surgery.
AB  - BACKGROUND: Red cell distribution width (RDW) is an important marker which
      reflects inflammatory activity in many chronic diseases. The objective of this
      study is to investigate the impact of RDW on morbidity and mortality before and
      after pediatric congenital heart surgery. METHODS: 107 patients with congenital
      heart disease, cardiac case group, and 70 patients, control group, without heart
      disease were retrospectively analyzed. Pre-, and postoperative and at discharge
      RDW of the cardiac patients were determined. Lengths of hospital and intensive
      care unit (ICU) stay and exited patients were determined. RESULTS: Mean lengths
      of ICU and hospital stay were 3.3 +/- 2.7 and 7.3 +/- 2.9 days. In control group,
      mean preoperative RDW was 12.6 +/- 1.4, while in cardiac case group it was
      significantly higher (15.1 +/- 3.5). In cardiac case group, postoperative RDW
      were significantly higher than preoperative period, while RDW at discharge were
      significantly lower than postoperative estimates. A significant and a positive
      correlation was detected between lengths of ICU and hospital stay and RDW. RDW of
      the exited patients were significantly higher than the survivors. CONCLUSIONS:
      This study demonstrates that RDW can be used as an important indicator in the
      prediction of morbidity and mortality during pre-, and postoperative period of
      the pediatric congenital heart disease surgery.

PMID- 24745022
TI  - Antihypertensive action of allantoin in animals.
AB  - The agonists of imidazoline I-1 receptors (I-1R) are widely used to lower blood
      pressure. It has been indicated that guanidinium derivatives show an ability to
      activate imidazoline receptors. Also, allantoin has a chemical stricture similar
      to guanidinium derivatives. Thus, it is of special interest to characterize the
      effect of allantoin on I-1R. In conscious male spontaneous hypertensive rats
      (SHRs), mean blood pressure (MBP) was recorded using the tail-cuff method.
      Furthermore, the hemodynamic analyses in catheterized rats were applied to
      measure the actions of allantoin in vivo. Allantoin decreased blood pressures in
      SHRs at 30 minutes, as the most effective time. Also, this antihypertensive
      action was shown in a dose-dependent manner from SHRs treated with allantoin.
      Moreover, in anesthetized rats, allantoin inhibited cardiac contractility and
      heart rate as showing in hemodynamic dP/dt max significantly. Also, the
      peripheral blood flow was markedly increased by allantoin. Both actions were
      diminished by efaroxan at the dose sufficient to block I-1R. Thus, we suggest
      that allantoin, as I-1R agonist, has the potential to develop as a new
      therapeutic agent for hypertension in the future. 

PMID- 24745024
TI  - Reinforced feedback in virtual environment for rehabilitation of upper extremity
      dysfunction after stroke: preliminary data from a randomized controlled trial.
AB  - OBJECTIVES: To study whether the reinforced feedback in virtual environment
      (RFVE) is more effective than traditional rehabilitation (TR) for the treatment
      of upper limb motor function after stroke, regardless of stroke etiology (i.e.,
      ischemic, hemorrhagic). DESIGN: Randomized controlled trial. Participants. Forty
      four patients affected by stroke. Intervention. The patients were randomized into
      two groups: RFVE (N = 23) and TR (N = 21), and stratified according to stroke
      etiology. The RFVE treatment consisted of multidirectional exercises providing
      augmented feedback provided by virtual reality, while in the TR treatment the
      same exercises were provided without augmented feedbacks. Outcome Measures. Fugl
      Meyer upper extremity scale (F-M UE), Functional Independence Measure scale
      (FIM), and kinematics parameters (speed, time, and peak). RESULTS: The F-M UE (P
      = 0.030), FIM (P = 0.021), time (P = 0.008), and peak (P = 0.018), were
      significantly higher in the RFVE group after treatment, but not speed (P =
      0.140). The patients affected by hemorrhagic stroke significantly improved FIM (P
      = 0.031), time (P = 0.011), and peak (P = 0.020) after treatment, whereas the
      patients affected by ischemic stroke improved significantly only speed (P =
      0.005) when treated by RFVE. CONCLUSION: These results indicated that some
      poststroke patients may benefit from RFVE program for the recovery of upper limb
      motor function. This trial is registered with NCT01955291.

PMID- 24745023
TI  - MicroRNAs in nonalcoholic fatty liver disease: novel biomarkers and prognostic
      tools during the transition from steatosis to hepatocarcinoma.
AB  - Nonalcoholic fatty liver disease (NAFLD) is a metabolic-related disorder ranging
      from steatosis to steatohepatitis, which may progress to cirrhosis and
      hepatocellular carcinoma (HCC). The influence of NAFLD on HCC development has
      drawn attention in recent years. HCC is one of the most common malignant tumors
      and the third highest cause of cancer-related death. HCC is frequently diagnosed
      late in the disease course, and patient's prognosis is usually poor. Early
      diagnosis and identification of the correct stage of liver damage during NAFLD
      progression can contribute to more effective therapeutic interventions, improving
      patient outcomes. Therefore, scientists are always searching for new sensitive
      and reliable markers that could be analysed through minimally invasive tests.
      MicroRNAs are short noncoding RNAs that act as posttranscriptional regulators of
      gene expression. Several studies identified specific miRNA expression profiles
      associated to different histological features of NAFLD. Thus, miRNAs are
      receiving growing attention as useful noninvasive diagnostic markers to follow
      the progression of NAFLD and to identify novel therapeutic targets. This review
      focuses on the current knowledge of the miRNAs involved in NAFLD and related HCC
      development, highlighting their diagnostic and prognostic value for the screening
      of NAFLD patients. 

PMID- 24745025
TI  - Plant virus expression vector development: new perspectives.
AB  - Plant made biologics have elicited much attention over recent years for their
      potential in assisting those in developing countries who have poor access to
      modern medicine. Additional applications such as the stockpiling of vaccines
      against pandemic infectious diseases or potential biological warfare agents are
      also under investigation. Plant virus expression vectors represent a technology
      that enables high levels of pharmaceutical proteins to be produced in a very
      short period of time. Recent advances in research and development have brought
      about the generation of superior virus expression systems which can be readily
      delivered to the host plant in a manner that is both efficient and cost
      effective. This review presents recent innovations in plant virus expression
      systems and their uses for producing biologics from plants. 

PMID- 24745026
TI  - Moderate intra-abdominal hypertension leads to anaerobic metabolism in the rectus
      abdominis muscle tissue of critically ill patients: a prospective observational
      study.
AB  - PURPOSE: We hypothesize that intra-abdominal hypertension (IAH) is associated
      with the presence of anaerobic metabolism in the abdominal rectus muscle (RAM)
      tissue of critically ill patients. METHODS: We included 10 adult, critically ill
      patients with intra-abdominal pressure (IAP) above 12 mmHg. Microdialysis
      catheters (CMA 60) were inserted into the RAM tissue. The samples were collected
      up to 72 hours after enrollment. RESULTS: The patients' median (IQR) APACHE II at
      inclusion was 29 (21-37); 7 patients were in shock. IAP was 14.5 (12.5-17.8) mmHg
      at baseline and decreased significantly over time, concomitantly with arterial
      lactate and vasopressors requirements. The tissue lactate-to-pyruvate (L/P) ratio
      was 49 (36-54) at the beginning of the study and decreased significantly
      throughout the study. Additionally, the tissue lactate, lactate-to-glucose (L/G)
      ratio, and glutamate concentrations changed significantly during the study. The
      correlation analysis showed that lower levels of pyruvate and glycerol were
      associated with higher MAP and abdominal perfusion pressures (APP) and that
      higher levels of glutamate were correlated to elevated IAP. CONCLUSIONS: Moderate
      IAH leads to RAM tissue anaerobic metabolism suggestive for hypoperfusion in
      critically ill patients. Correlation analysis supports the concept of using APP
      as the primary endpoint of resuscitation in addition to MAP and IAP.

PMID- 24745027
TI  - Recent insights in the paracrine modulation of cardiomyocyte contractility by
      cardiac endothelial cells.
AB  - The cardiac endothelium is formed by a continuous monolayer of cells that line
      the cavity of the heart (endocardial endothelial cells (EECs)) and the luminal
      surface of the myocardial blood vessels (intramyocardial capillary endothelial
      cells (IMCEs)). EECs and IMCEs can exercise substantial control over the
      contractility of cardiomyocytes by releasing various factors such as nitric oxide
      (NO) via a constitutive endothelial NO-synthase (eNOS), endothelin-1,
      prostaglandins, angiotensin II, peptide growth factors, and neuregulin-1. The
      purpose of the present paper is actually to shortly review recent new information
      concerning cardiomyocytes as effectors of endothelium paracrine signaling,
      focusing particularly on contractile function. The modes of action and the
      regulatory paracrine role of the main mediators delivered by cardiac endothelial
      cells upon cardiac contractility identified in cardiomyocytes are complex and not
      fully described. Thus, careful evaluation of new therapeutic approaches is
      required targeting important physiological signaling pathways, some of which have
      been until recently considered as deleterious, like reactive oxygen species.
      Future works in the field of cardiac endothelial cells and cardiac function will
      help to better understand the implication of these mediators in cardiac
      physiopathology. 

PMID- 24745028
TI  - Volumetric analysis of amygdala, hippocampus, and prefrontal cortex in therapy
      naive PTSD participants.
AB  - OBJECTIVE: In our study we have hypothesized that volume changes of amygdala,
      hippocampus, and prefrontal cortex are more pronounced in male posttraumatic
      stress disorder participants. MATERIAL AND METHODS: We have conducted a study of
      79 male participants who underwent MRI brain scanning. PTSD diagnosis was
      confirmed in 49 participants. After MRI was taken all scans were software based
      volume computed and statistically processed. RESULTS: We found that left amygdala
      is the most significant parameter for distinction between PTSD participants and
      participants without PTSD. There were no significant differences in volumes of
      hippocampi and prefrontal cortices. Roc curve method outlined left amygdala AUC =
      0.898 (95% CI = 0.830-0.967) and right amygdala AUC = 0.882 (95% CI = 0.810
      0.954) in the group of PTSD participants which makes both variables highly
      statistically significant. CONCLUSION: The present investigation revealed
      significant volume decrease of left amygdala in PTSD patients. Concerning
      important functions of the amygdala and her neuroanatomical connections with
      other brain structures, we need to increase number of participants to clarify the
      correlation between impared amygdala and possible other different brain
      structures in participants with PTSD.

PMID- 24745030
TI  - Insulin resistance, type 1 and type 2 diabetes, and related complications:
      current status and future perspective.

PMID- 24745029
TI  - Clinicopathological factors affecting survival and recurrence after initial
      hepatectomy in non-B non-C hepatocellular carcinoma patients with comparison to
      hepatitis B or C virus.
AB  - We evaluated clinicopathological factors affecting survival and recurrence after
      initial hepatectomy in non-B non-C (NBNC) hepatocellular carcinoma (HCC) patients
      with comparison to hepatitis B or C virus, paying attention to relationship
      between alcohol consumption and histopathological findings. The medical records
      on the 201HCC patients who underwent initial hepatectomy between January 2000 and
      April 2013 were retrospectively reviewed. NBNC patients had higher prevalence of
      hypertension (47.4%), diabetes mellitus (35.5%), alcohol consumption (>20 g/day)
      (61.8%), and preserved liver function than hepatitis B or C patients. The 5-year
      survival rate of NBNC patients (74.1%) was significantly better than hepatitis B
      (49.1%) or C (65.0%) patients (NBNC versus B, P = 0.031). Among the NBNC
      patients, there was no relationship between alcohol consumption and
      clinicopathological findings including nonalcoholic fatty liver disease activity
      score (NAS). However, the 5-year OS and RFS rates in the alcohol-unrelated NBNC
      patients tend to be better than in the alcohol-related. By multivariate analysis,
      independent factors for OS in NBNC patients were Child-Pugh B/C, intrahepatic
      metastasis (im), and extrahepatic recurrence. NBNC patients, who were highly
      associated with lifestyle-related disease and preserved liver function, had
      significantly better prognosis compared to hepatitis B/C patients; however, there
      was no association between alcohol consumption and histopathological findings. 

PMID- 24745032
TI  - Engineering nanointerfaces for nanocatalysis.
AB  - The interface, referred to as the boundary between two phases, has been
      demonstrated to play a critical role in catalysis. Fundamental understanding of
      interfacial phenomena occurring in catalysis will favor the rational design of
      high-performance catalysts. With the thriving of nanoscience, the nanointerface
      has also received tremendous attention in nanocatalysis. In this review, we focus
      on the recent advances in the delicate design and the fine control of various
      complex nanomaterials with well-defined interfaces based on progress in nano
      synthetic methodologies, including metal-metal oxide, metal-metal, metal-non
      oxide and metal in confined spaces. Then the challenging issues in the synthetic
      control of a nanointerface, based on the authors' experiences, are discussed.
      Finally, the prospects and outlooks for engineering nanointerfaces for
      nanocatalysis towards renewable energy are presented. 

PMID- 24745033
TI  - Colorimetric detection of copper and efficient removal of heavy metal ions from
      water by diamine-functionalized SBA-15.
AB  - SBA-15 functionalized with N-[3-(trimethoxysilyl)propyl]ethylene-diamine (TPED)
      was synthesized and used for the colorimetric detection of Cu(2+) and removal of
      heavy metal ions in aqueous solutions. Compared to free SBA-15, the adsorption
      ability of diamine-functionalized SBA-15 (depicted as SBA-TPED) increased
      remarkably, the maximum adsorption capacity of SBA-TPED for Cu(2+), Pb(2+) and
      Zn(2+) was 27.22, 96.43 and 12.16 mg g(-1), respectively. Furthermore, SBA-TPED
      exhibits high selectivity for Cu(2+) with the relative selectivity coefficient of
      SBA-TPED for Cu(2+)/Pb(2+) being over 10 and for Cu(2+)/Zn(2+) being over 60. The
      naked-eye detection limit of SBA-TPED for Cu(2+) is 0.95 ppm, and the
      determination of Cu(2+) in real water samples also displays satisfactory results.
      Moreover, SBA-TPED possesses fast kinetics for removing Cu(2+) with a saturation
      time of less than 30 min, and can be regenerated by simple acid treatment. 

PMID- 24745031
TI  - The protective effects of insulin and natural honey against hippocampal cell
      death in streptozotocin-induced diabetic rats.
AB  - We investigated the effects of insulin and honey as antioxidants to prevent the
      hippocampal cell death in streptozotocin-induced diabetic rats. We selected sixty
      Wister rats (5 groups of 12 animals each), including the control group (C), and
      four diabetic groups (control (D) and 3 groups treated with insulin (I), honey
      (H), and insulin plus honey (I + H)). Diabetes was induced by streptozotocin
      injection (IP, 60 mg/kg). Six weeks after the induction of diabetes, the group I
      received insulin (3-4 U/kg/day, SC), group H received honey (5 mg/kg/day, IP),
      and group I + H received a combination of the above at the same dose. Groups C
      and D received normal saline. Two weeks after treatment, rats were sacrificed and
      the hippocampus was extracted. Neuronal cell death in the hippocampal region was
      examined using trypan blue assay, "H & E" staining, and TUNEL assay. Cell
      viability assessment showed significantly lower number of living cells in group D
      than in group C. Besides, the mean number of living cells was significantly
      higher in group I, H, and I + H compared to group D. Therefore, it can be
      concluded that the treatment of the diabetic rats with insulin, honey, and a
      combination of insulin and honey can prevent neuronal cell death in different
      hippocampal areas of the studied samples.

PMID- 24745034
TI  - Practical measures for reducing the risk of environmental contamination in shale
      energy production.
AB  - Gas recovery from shale formations has been made possible by advances in
      horizontal drilling and hydraulic fracturing technology. Rapid adoption of these
      methods has created a surge in natural gas production in the United States and
      increased public concern about its environmental and human health effects. We
      surveyed the environmental literature relevant to shale gas development and
      studied over fifteen well sites and impoundments in West Virginia to evaluate
      pollution caused by air emissions, light and noise during drilling. Our study
      also characterized liquid and solid waste streams generated by drilling and
      hydraulic fracturing and evaluated the integrity of impoundments used to store
      fluids produced by hydraulic fracturing. While most shale gas wells are completed
      with little or no environmental contamination, we found that many of the problems
      associated with shale gas development resulted from inattention to accepted
      engineering practices such as impoundment construction, improper liner
      installation and a lack of institutional controls. Recommendations are provided
      based on the literature and our field studies. They will address not all but a
      great many of the deficiencies that result in environmental release of
      contaminants from shale gas development. We also identified areas where new
      technologies are needed to fully address contaminant releases to air and water. 

PMID- 24745036
TI  - A droplet-based pH regulator in microfluidics.
AB  - In this paper, we develop a strategy to form on-demand droplets with specific pH
      values. The pH control is based on electrolysis of water in microfluidics, and
      the produced hydrogen and hydroxyl ions are separated and confined in individual
      containers during the droplet generation, triggered by a pressure pulse. By
      tuning the applied voltages and pressure pulses, we can control on demand the pH
      value in a droplet. 

PMID- 24745035
TI  - The high antioxidative power of quercetin (aglycone flavonoid) and its glycone
      (rutin) avert high cholesterol diet induced hepatotoxicity and inflammation in
      Swiss albino mice.
AB  - The present study demonstrates for the first time the protective role of two
      common flavonoids, quercetin and its glycone rutin, against high cholesterol diet
      (2%) induced hepatotoxicity and inflammation. Swiss albino mice were given either
      a standard laboratory diet (control), high cholesterol diet (HCD) or high
      cholesterol diet along with quercetin or rutin (100 mg kg(-1) body weight) in
      their respective groups. The HCD mice exhibited a gain in body weight,
      significant rise in serum and hepatic level of total cholesterol, triglyceride,
      liver function enzymes, lipid peroxidation, and pro-inflammatory cytokines (P <
      0.05). Histopathological studies showed hepatic fat accumulation and tissue
      disintegration. There was significant depletion of major hepatic antioxidants (P
      < 0.05). Immunoblot studies revealed a high expression of redox sensitive
      transcription factors NF-kappaB and TNF-alpha. A subsequent rise in the mRNA
      expression of inflammatory markers like C reactive protein and inducible nitric
      oxide synthase 2 were also found from the RT-PCR study. Simultaneous treatment
      with quercetin or rutin along with HCD significantly prevented the gains in body
      weight, lipid level, liver function enzymes, lipid peroxidation level and
      expression of inflammatory markers. The restoration of hepatic antioxidant
      homeostasis and hepatic morphology has also been observed. Hence, the present
      study illustrates the hypolipidemic, hepatoprotective and anti-inflammatory
      effects of two similar flavonoids. 

PMID- 24745037
TI  - Inverted process for graphene integrated circuits fabrication.
AB  - CMOS compatible 200 mm two-layer-routing technology is employed to fabricate
      graphene field-effect transistors (GFETs) and monolithic graphene ICs. The
      process is inverse to traditional Si technology. Passive elements are fabricated
      in the first metal layer and GFETs are formed with buried gate/source/drain in
      the second metal layer. Gate dielectric of 3.1 nm in equivalent oxide thickness
      (EOT) is employed. 500 nm-gate-length GFETs feature a yield of 80% and fT/fmax =
      17 GHz/15.2 GHz RF performance. A high-performance monolithic graphene frequency
      multiplier is demonstrated using the proposed process. Functionality was
      demonstrated up to 8 GHz input and 16 GHz output. The frequency multiplier
      features a 3 dB bandwidth of 4 GHz and conversion gain of -26 dB. 

PMID- 24745039
TI  - Author response.

PMID- 24745038
TI  - Photoconversion changes bilin chromophore conjugation and protein secondary
      structure in the violet/orange cyanobacteriochrome NpF2164g3' [corrected].
AB  - Cyanobacteriochromes (CBCRs) are cyanobacterial photoreceptors distantly related
      to phytochromes. All CBCRs examined to date utilize a conserved Cys residue to
      form a covalent thioether linkage to the bilin chromophore. In the insert-Cys
      CBCR subfamily, a second conserved Cys can covalently link to the bilin C10
      methine bridge, allowing detection of near-UV to blue light. The best understood
      insert-Cys CBCR is the violet/orange CBCR NpF2164g3 from Nostoc punctiforme,
      which has a stable second linkage in the violet-absorbing dark state.
      Photoconversion of NpF2164g3 leads to elimination of the second linkage and
      formation of an orange-absorbing photoproduct. We recently reported NMR chemical
      shift assignments for the orange-absorbing photoproduct state of NpF2164g3. We
      here present equivalent information for its violet-absorbing dark state. In both
      photostates, NpF2164g3 is monomeric in solution and regions containing the two
      conserved Cys residues essential for photoconversion are structurally disordered.
      In contrast to blue light receptors such as phototropin, NpF2164g3 is less
      structurally ordered in the dark state than in the photoproduct. The insert-Cys
      insertion loop and C-terminal helix exhibit light-dependent structural changes.
      Moreover, a motif containing an Asp residue also found in other CBCRs and in
      phytochromes adopts a random-coil structure in the dark state but a stable alpha
      helix structure in the photoproduct. NMR analysis of the chromophore is
      consistent with a less ordered dark state, with A-ring resonances only resolved
      in the photoproduct. The C10 atom of the bilin chromophore exhibits a drastic
      change in chemical shift upon photoconversion, changing from 34.5 ppm (methylene)
      in the dark state to 115 ppm (methine) in the light-activated state. Our results
      provide structural insight into the two-Cys photocycle of NpF2164g3 and the
      structurally diverse mechanisms used for light perception by the larger
      phytochrome superfamily. 

PMID- 24745040
TI  - Author response.

PMID- 24745041
TI  - LeishMan recommendations for treatment of cutaneous and mucosal leishmaniasis in
      travelers, 2014.
AB  - BACKGROUND: Treatment of cutaneous leishmaniasis (CL) and mucosal leishmaniasis
      (ML) in travelers is still controversial. Over the last decade, national and
      international consortia have published recommendations for treating CL in
      travelers. These guidelines harmonize many issues, but there are some
      discrepancies. METHODS: Leishmania parasites causing CL can now be genotyped by
      polymerase chain reaction techniques for detecting Leishmania DNA. Therefore,
      treatment recommendations can now be species based rather than based on
      geographical exposure. To review the evidence on which the recommendations were
      based, "LeishMan" (Leishmaniasis Management), a group of experts from 13
      institutions in eight European countries, performed a PubMed MEDLINE) literature
      search and considered unpublished evidence and the experts' own personal
      experiences. The Oxford evidence grading system was used to evaluate the
      information. RESULTS AND CONCLUSION: In this article, the authors provide
      practical treatment recommendations for imported CL and ML in Europe, drawn up
      from the review by the European experts.

PMID- 24745042
TI  - Author's reply.

PMID- 24745043
TI  - Author's reply.

PMID- 24745044
TI  - Author's reply.

PMID- 24745045
TI  - Quantitative transcriptional changes associated with chlorosis severity in mosaic
      leaves of tobacco plants infected with Cucumber mosaic virus.
AB  - Cucumber mosaic virus (CMV) causes mosaic disease in inoculated tobacco plants.
      Coat protein (CP) is one of the major virulence determinants of CMV, and an amino
      acid substitution at residue 129 in CP alters the severity of chlorosis, such as
      pale green chlorosis and white chlorosis, in symptomatic tissues of mosaic leaves
      of infected tobacco. In this study, we compared the transcriptomes of chlorotic
      tissues infected with the wild-type pepo strain of CMV and two strains carrying
      CP mutants with diverse chlorosis severity. Differential gene expression analysis
      showed that CMV inoculation appeared to have similar effects on the
      transcriptional expression profiles of the symptomatic chlorotic tissues, and
      only the magnitude of expression differed among the different CMVs. Gene ontology
      analysis with biological process and cellular component terms revealed that many
      nuclear genes related to abiotic stress responses, including responses to
      cadmium, heat, cold and salt, were up-regulated, whereas chloroplast- and
      photosynthesis-related genes (CPRGs) were down-regulated, in the chlorotic
      tissues. Interestingly, the level of CPRG down-regulation was correlated with the
      severity of chlorosis. These results indicate that CP mutation governs the
      repression level and mRNA accumulation of CPRGs, which are closely associated
      with the induction of chlorosis.

PMID- 24745046
TI  - Ralstonia solanacearum type III secretion system effector Rip36 induces a
      hypersensitive response in the nonhost wild eggplant Solanum torvum.
AB  - Ralstonia solanacearum is a Gram-negative soil-borne bacterium that causes
      bacterial wilt disease in more than 200 plant species, including economically
      important Solanaceae species. In R. solanacearum, the hypersensitive response and
      pathogenicity (Hrp) type III secretion system is required for both the ability to
      induce the hypersensitive response (HR) in nonhost plants and pathogenicity in
      host plants. Recently, 72 effector genes, called rip (Ralstonia protein injected
      into plant cells), have been identified in R. solanacearum RS1000. RS1002, a
      spontaneous nalixidic acid-resistant derivative of RS1000, induced strong HR in
      the nonhost wild eggplant Solanum torvum in an Hrp-dependent manner. An
      Agrobacterium-mediated transient expression system revealed that Rip36, a
      putative Zn-dependent protease effector of R. solanacearum, induced HR in S.
      torvum. A mutation in the putative Zn-binding motif (E149A) completely abolished
      the ability to induce HR. In agreement with this result, the RS1002-derived
      Deltarip36 and rip36E149A mutants lost the ability to induce HR in S. torvum. An
      E149A mutation had no effect on the translocation of Rip36 into plant cells.
      These results indicate that Rip36 is an avirulent factor that induces HR in S.
      torvum and that a putative Zn-dependent protease motif is essential for this
      activity.

PMID- 24745047
TI  - Self-assembly of DNA nanotubes with defined diameters and lengths.
AB  - Nanotubes with different sizes can be readily assembled from simple DNA
      nanomotifs, which consist of just a few unique DNA sequences. Such structurally
      well-defi ned DNA-nanotubes will have great potential in many technological
      applications ranging from drug delivery, to determination of biomacromolecular 3D
      structures, to nanoplasmonic devices.

PMID- 24745048
TI  - Smoking and mental illness-time to break the link.

PMID- 24745049
TI  - Uranium mines: lung disease and mistrust among Native Americans.

PMID- 24745050
TI  - Might statins prevent delirium in intensive care units?

PMID- 24745051
TI  - Mass production of graphene quantum dots by one-pot synthesis directly from
      graphite in high yield.
AB  - One of the most efficient and straightforward methods for production of graphene
      quantum dots (GQDs) could be their direct preparation from graphite powder by one
      pot synthesis using high-powered microwave irradiation. It is believed that in
      this way, graphite can be multiply broken by repeated redox reactions, which
      leads to a high yield and mass production.

PMID- 24745053
TI  - First stem cell treatment for BPD in preterm infants.

PMID- 24745052
TI  - Effectiveness of tuberculosis preventive therapy in gold miners.

PMID- 24745054
TI  - Bulgaria lags behind Europe in pollution and smoking targets.

PMID- 24745055
TI  - Responsible mining.

PMID- 24745056
TI  - Tuberculosis in black and white.

PMID- 24745057
TI  - High- versus low-quality graphene: a mechanistic investigation of electrografted
      diazonium-based films for growth of polymer brushes.
AB  - Electrografting using aryldiazonium salts provides a fast and efficient technique
      to functionalize commercially available 3-5 layered graphene (vapour-deposited)
      on nickel. In this study, Raman spectroscopy is used to quantify the grafting
      efficiency of cyclic voltammetry which is one of the most versatile, yet simple,
      electrochemical techniques available. To a large extent the number of
      defects/substituents introduced to the basal plane of high-quality graphene by
      this procedure can be controlled through the sweeping conditions employed. After
      extended electrografting the defect density reaches a saturation level ( ~ 10(13)
      cm(-2)) which is independent of the quality of the graphene expressed through its
      initial content of defects. However, it is reached within fewer voltammetric
      cycles for low-quality graphene. Based on these results it is suggested that the
      grafting occurs (a) directly at defect sites for, in particular, low-quality
      graphene, (b) directly at the basal plane for, in particular, high-quality
      graphene, and/or (c) at already grafted molecules to give a mushroom-like film
      growth for all films. Moreover, it is shown that a tertiary alkyl bromide can be
      introduced at a given surface density to serve as radical initiator for surface
      initiated atom transfer radical polymerization (SI-ATRP). Brushes of poly(methyl
      methacrylate) are grown from these substrates, and the relationship between
      polymer thickness and sweeping conditions is studied.

PMID- 24745058
TI  - Conjugated polymer shells on colloidal templates by seeded Suzuki-Miyaura
      dispersion polymerization.
AB  - The self-assembly of colloidal conjugated polymers presents a versatile and
      powerful oute towards new functional optoelectronic materials and devices.
      However, this strategy relies on the existence of chemical protocols to prepare
      highly monodisperse colloids of conjugated polymers in high yields. Here, a
      recently developed Suzuki-Miyaura dispersion polymerization method is adopted to
      synthesize core-shell particles, in which a conjugated polymer shell is grown
      onto non-conjugated organic and inorganic colloidal templates. By chemically
      anchoring aryl halide groups at the particle surface, a conjugated polymer shell
      can be attached to a wide variety of organic and inorganic microparticles. In
      this way, both spherical and non-spherical hybrid conjugated polymer particles
      are prepared, and it is shown that the method can be applied to a variety of
      conjugated polymers. This new method offers independent control of the size,
      shape and photophysical properties of these novel conjugated polymer particles.

PMID- 24745059
TI  - Multi-responsive and logic controlled release of DNA-gated mesoporous silica
      vehicles functionalized with intercalators for multiple delivery.
AB  - Novel DNA-gated mesoporous silica nanoparticle (MSN) vehicles functionalized with
      disulfide-linked acridinamine intercalators are constructed for multi-responsive
      controlled release. The DNA-gated MSN vehicles release cargo encapsulated in the
      MSN pores under different stimuli, including disulfide reducing agents, elevated
      temperature, and deoxyribonuclease I (DNase I), for codelivery of drugs and
      DNA/genes in different forms. Furthermore, the cascade release of encapsulated
      and intercalative drugs is controlled by AND logic gates in combination of dual
      stimuli. The ingeniously designed DNA-gated MSN vehicles integrates multiple
      responses and AND logic gate operations into a single smart nanodevice not only
      for codelivery of drugs and DNA/genes but also for cascade release of two drugs
      and has promising biological applications to meet diverse requirements of
      controlled release.

PMID- 24745060
TI  - Description of the use of contrast-enhanced ultrasonography in four dogs with
      pancreatic tumours.
AB  - Canine pancreatic tumours are rare compared to human medicine and the detection
      and differentiation of pancreatic neoplasia is challenging with B-mode
      ultrasonography, which often leads to late clinical diagnosis and poor prognosis.
      This case report describes the findings of contrast-enhanced ultrasonography in
      four dogs with pancreatic adenocarcinoma or insulinoma. B-mode ultrasonography of
      the pancreas revealed a hypoechoic nodule in three dogs and heterogenous tissue
      in one dog. Contrast-enhanced ultrasonography was able to differentiate between
      two tumour types: adenocarcinomas showed hypoechoic and hypovascular lesions,
      whereas insulinomas showed uniformly hypervascular lesions. Contrast-enhanced
      ultrasonography findings were confirmed by cytology and/or histopathology. The
      results demonstrated that contrast-enhanced ultrasonography was able to establish
      different enhancement patterns between exocrine (adenocarcinoma) and endocrine
      (insulinoma) tumours in dogs.

PMID- 24745061
TI  - New developments with vagus nerve stimulation therapy.
AB  - The vagus nerve is a major component of the autonomic nervous system, has an
      important role in the regulation of metabolic homeostasis, and plays a key role
      in the neuro-endocrine-immune axis. Vagus nerve stimulation (VNS) refers to any
      technique that stimulates the vagus nerve. Left cervical VNS is an approved
      therapy for refractory epilepsy and treatment-resistant depression. Right
      cervical VNS has proven effective for treating heart failure in preclinical
      studies and a Phase II clinical trial. The effectiveness of noninvasive
      transcutaneous VNS for epilepsy, depression, and other conditions has not been
      investigated beyond small pilot studies. The relationship between depression,
      inflammation, and cardiovascular, cerebrovascular, and metabolic syndromes might
      be mediated by the vagus nerve. Transcutaneous VNS deserves further study as an
      antidepressant therapy and for its potential effect on physiological biomarkers
      associated with depression morbidity and mortality.

PMID- 24745062
TI  - You need to be an advocate for our profession.

PMID- 24745063
TI  - Advancing technologist education.

PMID- 24745064
TI  - Impact of the blood sampling site on time-concentration drug profiles following
      intravenous or buccal drug administration.
AB  - The aim of this study was to examine the effect of the sampling site on the drug
      concentration-time profile, following intravenous or buccal (often called 'oral
      transmucosal') drug administration. Buprenorphine (20 MUg/kg) was administered IV
      or buccally to six cats. Blood samples were collected from the carotid artery and
      the jugular and medial saphenous veins for 24 h following buprenorphine
      administration. Buprenorphine concentration-time data were examined using
      noncompartmental analysis. Pharmacokinetic parameters were compared using the
      Wilcoxon signed rank test, applying the Bonferroni correction. Significance was
      set at P < 0.05. Following IV administration, no difference among the sampling
      sites was found. Following buccal administration, maximum concentration [jugular:
      6.3 (2.9-9.8), carotid: 3.4 (1.9-4.9), medial saphenous: 2.5 (1.7-4.1) ng/mL],
      area under the curve [jugular: 395 (335-747), carotid: 278 (214-693), medial
      saphenous: 255 (188-608) ng.min/mL], and bioavailability [jugular: 47 (34-67),
      carotid: 32 (20-52), medial saphenous: 23 (16-55)%] were higher in the jugular
      vein than in the carotid artery and medial saphenous vein. Jugular venous blood
      sampling is not an acceptable substitute for arterial blood sampling following
      buccal drug administration.

PMID- 24745065
TI  - Pharmacokinetics and preliminary safety data of a single oral dose of bosentan, a
      dual endothelin receptor antagonist, in cats.
AB  - The objective of this study was to evaluate the pharmacokinetic properties and
      adverse effect profile of single-dose oral bosentan, a dual endothelin receptor
      antagonist, in healthy cats. Pharmacokinetic parameters were determined following
      a single mean +/- SD oral dose of 3.2 +/- 0.6 mg/kg of bosentan in 6 adult cats.
      Blood was collected for quantification of bosentan via high-performance liquid
      chromatography with ultraviolet detection. Blood and urine were evaluated for
      CBC, plasma biochemical profile, and urinalysis, and repeat physical examinations
      were performed to evaluate for adverse effects. The mean terminal half-life of
      bosentan was 20.4 +/- 17.2 h. The mean peak plasma concentration was 0.49 +/-
      0.24 g/mL, and the mean time to maximum plasma concentration was 6.8 +/- 8.6 h.
      The area under the curve was 5.14 +/- 3.81 h.MUg/mL. Oral bosentan tablets were
      absorbed in cats, and no clinically important adverse events were noted. Further
      evaluation of repeat dosing, investigation into the in vivo efficacy of
      decreasing endothelin-1 concentrations in cats, as well as safety in conjunction
      with other medications is warranted.

PMID- 24745066
TI  - Tactical tenure manoeuvres.

PMID- 24745067
TI  - The democracy carousel.

PMID- 24745068
TI  - Cancer crossroads.

PMID- 24745069
TI  - Practical nonsense.

PMID- 24745070
TI  - Publishing: Credit where credit is due.

PMID- 24745071
TI  - A radiographic study on the utility of cranial vault outlines for positive
      identifications.
AB  - A standard method for positive identification is the use of antemortem and
      postmortem radiographic comparisons. The purpose of this research is to test the
      visual accuracy of antemortem and postmortem radiographic comparisons of cranial
      vault outlines and to evaluate their uniqueness using geometric morphometric
      methods. A sample of 106 individuals with varying levels of education and
      forensic case experience participated in a visual accuracy test. Of the 106
      individuals, only 42% correctly assigned all of the radiographs, with accuracy
      rates ranging from 70 to 93% for each radiographic comparison. Vault shape was
      further examined using elliptic Fourier analysis, and paired t-tests were
      computed on the first 10 principal components accounting for 100% of the
      variance, which found no significant differences. The visual accuracy test and
      elliptic Fourier analysis shows that vault outlines may not be unique enough for
      positive identifications when used as a sole indicator.

PMID- 24745072
TI  - Phytophotodermatitis.
AB  - Phytophotodermatitis is a phototoxic cutaneous eruption due to skin exposure to
      furocourmarins combined with ultraviolet light. Bizzare linear patterns, ranging
      from erythema to bullae with residual hyperpigmentaion, is the clinical clue to
      this diagnosis. Avoidance of furocoumarins in direct sunlight can prevent
      recurrences.

PMID- 24745073
TI  - The effects of sharp-force thoracic trauma on the rate and pattern of
      decomposition.
AB  - Given the multiple factors that may alter the rate of decomposition, one of the
      more difficult tasks that anthropologists and pathologists face is determining of
      the postmortem interval (PMI). While trauma has been widely accepted as being
      among those factors, recent published studies have contradicted this premise.
      However, major issues exist with these studies. Consequently, this study was
      designed to simulate a more realistic setting in an effort to settle this
      discrepancy in the literature. This study utilized eight porcine remains; three
      of which received incised wounds penetrating the thoracic cavity, three others
      received nonpenetrating wounds, and two were designated nontrauma controls.
      Measurements included evaluating the total body score (TBS) on temporal and
      accumulated degree days (ADD). Using a two-way repeated measures ANOVA, the
      results of this study found that while trauma does have an influence in the
      pattern of decomposition, it does not influence the rate of decomposition.

PMID- 24745074
TI  - Effect of extraction procedure and gas chromatography temperature program on
      discrimination of MDMA exhibits.
AB  - Analysis of impurities in seized MDMA tablets can be used to determine the
      synthesis method used and to identify links among exhibits. However, no
      standardized method exists to generate impurity profiles, limiting comparisons
      among different laboratories. This research investigated the effect of extraction
      procedure and gas chromatography temperature program on the resulting impurity
      profiles. Five exhibits were extracted using liquid-liquid extraction (LLE) and
      headspace solid-phase microextraction (HS-SPME), then analyzed using two
      different temperature programs. Profiles were statistically assessed using
      principal components analysis. While LLE was more reproducible, more compounds
      were extracted using HS-SPME, thus providing more informative chemical profiles.
      The longer temperature program (53 min vs. 36 min) allowed greater discrimination
      of exhibits, due to improved precision as a result of an extended hold time (12
      min). This research further highlights the need for standardized extraction and
      analysis procedures to allow comparison of chemical profiles generated in
      different laboratories.

PMID- 24745075
TI  - Use of postmortem temperature decay response surface plots of heat transport in
      the human eye to predict time of death.
AB  - A finite element heat transfer model of the human eye was previously constructed
      and applied to experimental postmortem temperature decay curves collected in
      eyeballs of ten human bodies. The model was applied in the early postmortem
      period of 0-24 h under conditions of natural convection-radiation. Based upon
      this previous model, response surfaces for postmortem temperature decay were
      constructed based upon variable ranges of the natural convective-radiation heat
      transfer coefficient from 7-13 W/m2 K, ambient temperatures of 10-33 degrees C,
      and times of 0-24 h. Mathematical equations to describe these response surfaces
      have been developed. This response surface method is demonstrated for use by
      coroners/medical personnel to estimate time of death from recorded field
      temperature data collected over a 30-min period. Sensitivity of the model to
      small changes in the key variable of ambient temperature is explored. The
      response surface model is applied to two cases of previously collected
      experimental eyeball temperature data. This response surface model method is only
      valid for constant surrounding temperatures, conditions of natural convection, no
      radiation effects, and postmortem times of 0-24 h.

PMID- 24745076
TI  - Comparative analysis of insect succession data from Victoria (Australia) using
      summary statistics versus preceding mean ambient temperature models.
AB  - Minimum postmortem interval (mPMI) can be estimated with preceding mean ambient
      temperature models that predict carrion taxon pre-appearance interval. But
      accuracy has not been compared with using summary statistics (mean +/- SD of
      taxon arrival/departure day, range, 95% CI). This study collected succession data
      from ten experimental and five control (infrequently sampled) pig carcasses over
      two summers (n = 2 experimental, n = 1 control per placement date). Linear and
      exponential preceding mean ambient temperature models for appearance and
      departure times were constructed for 17 taxa/developmental stages. There was
      minimal difference in linear or exponential model success, although arrival
      models were more often significant: 65% of linear arrival (r2 = 0.09-0.79) and
      exponential arrival models (r2 = 0.05-81.0) were significant, and 35% of linear
      departure (r2 = 0.0-0.71) and exponential departure models (r2 = 0.0-0.72) were
      significant. Performance of models and summary statistics for estimating mPMI was
      compared in two forensic cases. Only summary statistics produced accurate mPMI
      estimates.

PMID- 24745077
TI  - An empirical study of rape in the context of multiple murder.
AB  - In recent years, multiple homicide offending has received increased research
      attention from criminologists; however, there is mixed evidence about the role of
      rape toward the perpetration of multiple murder. Drawing on criminal career data
      from a nonprobability sample of 618 confined male homicide offenders selected
      from eight U.S. states, the current study examines the role of rape as a
      predictor of multiple homicide offending. Bivariate analyses indicated a
      significant association between rape and murder charges. Multivariate path
      regression models indicated that rape had a significant and robust association
      with multiple murder. This relationship withstood the confounding effects of
      kidnapping, prior prison confinement, and prior murder, rape, and kidnapping.
      These results provide evidence that rape potentially serves as a gateway to
      multiple murder for some serious offenders. Suggestions for future research are
      proffered.

PMID- 24745078
TI  - Acute influence of alcohol, THC or central stimulants on violent suicide: A
      Swedish population study.
AB  - Alcohol and substance abuse in general is a risk factor for suicide, but very
      little is known about the acute effect in relation to suicide method. Based on
      information from 18,894 medico-legal death investigations, including
      toxicological findings and manner of death, did the present study investigate
      whether acute influence of alcohol, tetrahydrocannabinol (THC), or central
      stimulants (amphetamine and cocaine) was related to the use of a violent suicide
      method, in comparison with the nonviolent method self-poisoning and alcohol
      /illicit drug-negative suicide decedents. Multivariate analysis was conducted,
      and the results revealed that acute influence of THC was related to using the
      violent suicide method-- jumping from a height (RR 1.62; 95% CI 1.01-2.41).
      Alcohol intoxication was not related to any violent method, while the central
      stimulant-positive suicide decedent had a higher, albeit not significant, risk of
      several violent methods. The study contributes with elucidating suicide methods
      in relation to acute intoxication.

PMID- 24745079
TI  - Post-thoracotomy pain in children and adolescence: a retrospective cross
      sectional study.
AB  - OBJECTIVE: We sought to determine the prevalence of chronic post-thoracotomy
      pain, defined as persistent or recurring incisional pain for at least 2 months
      after thoracotomy, in children. DESIGN: Retrospective cross-sectional study.
      SETTING: Quaternary pediatric teaching hospital. SUBJECTS: Patients who underwent
      a lateral thoracotomy from January 2005 to December 2007 at the Royal Children's
      Hospital, Melbourne, Australia. METHODS: Eligible patients were sent a
      questionnaire for telephonic completion with a researcher, with assistance from
      the parents if required. RESULTS: Of the 87 patients eligible to participate, 51
      (59%) completed questionnaires. The majority of respondents was male (65%),
      underwent a single thoracotomy (84%; range 1-3), and were non-elective operations
      (71%). The median age at first thoracotomy was 5.7 (interquartile range [IQR] 2
      14.2) years. The median age at questionnaire completion was 9.0 (IQR 5.4-17.9)
      years, with 3.6 (IQR 2.8-4.1) years between thoracotomy and time of questionnaire
      completion. Three patients (6%) scored >=12 on self-report versions of the Leeds
      Assessment of Neuropathic Symptoms and Signs pain scale. Of these, only one
      patient complained of current post-thoracotomy pain. All three patients had a
      single thoracotomy and were older (mean age 14.2 years) at the time of
      thoracotomy. The rate of post-thoracotomy pain calculated using the binomial
      exact method is 1.96% (95% confidence interval 0-10.4%). CONCLUSIONS: Our study
      reports a low prevalence of post-thoracotomy pain in childhood and adolescence,
      and stands in contrast to previously published adult data.

PMID- 24745080
TI  - Variability and similarity of gait as evaluated by joint angles: implications for
      forensic gait analysis.
AB  - Closed-circuit television (CCTV) footage is used in criminal investigations to
      compare perpetrators with suspects. Usually, incomplete gait cycles are
      collected, making evidential gait analysis challenging. This study aimed to
      analyze the discriminatory power of joint angles throughout a gait cycle. Six
      sets from 12 men were collected. For each man, a variability range VR (mean +/-
      1SD) of a specific joint angle at a specific time point (a gait cycle was 100
      time points) was calculated. In turn, each individual was compared with the 11
      others, and whenever 1 of these 11 had a value within this individual's VR, it
      counted as positive. By adding the positives throughout the gait cycle, we
      created simple bar graphs; tall bars indicated a small discriminatory power,
      short bars indicated a larger one. The highest discriminatory power was at time
      points 60-80 in the gait cycle. We show how our data can assess gait data from an
      actual case.

PMID- 24745081
TI  - Quick response code in acrylic denture: will it respond when needed?
AB  - Use of acids and other caustic substances in destroying the human body to avoid
      personal identification is drawing great deal of attention in recent times. With
      rapid industrial growth, incidence of industrial disasters has increased. In an
      event of chemical industry disaster, human identification can become a challenge.
      Embedding bar codes and other electronic means for identification in denture have
      proved to be a novel innovation in identification of edentulous patients.
      However, the validity of this method in events of chemical extremes has not been
      assessed. Hence, the study was undertaken to know the effect of different acids
      on dentures embedded with quick response codes. Results of this study indicate
      that simple bar code can be readable up to 33 h after acid treatment. With
      minimal armamentarium, bar code can be generated incorporating large data into
      it, providing it to be a cheap and reliable means of denture identification.

PMID- 24745082
TI  - [Not Available].

PMID- 24745083
TI  - Influence of paraquat on Chrysomya megacephala (Fabricius) (Diptera:
      Calliphoridae) infesting minced-beef substrates in Kelantan, Malaysia.
AB  - This study investigated the influence of paraquat, a prevalent poison used by
      suicides, on initial oviposition and development of Chrysomya megacephala
      (Fabricius) using minced-beef substrates. Paraquat in lethal dose for human (40
      mg/kg), two times the lethal dose (80 mg/kg) and five times the lethal dose (200
      mg/kg) were mixed thoroughly with respective minced-beef substrates (1 kg each)
      that were decomposed in a shaded habitat fully protected from rain. Results of
      four replications of the above experiment revealed that the presence of paraquat
      neither delayed initial oviposition nor prolonged the developmental stages of C.
      megacephala. Therefore, estimation of postmortem interval (PMI) based on
      empirical baseline data obtained using animal models devoid of any poisons would
      still be appropriate for estimating PMI in paraquat-related deaths.

PMID- 24745084
TI  - Women victims of violent partners: the Italian situation amid culture and
      psychopathology.
AB  - In 2006, the Italian National Institute of Statistics (ISTAT) conducted a survey
      over the entire national territory of women victims of sexual, physical, and
      psychologic violence, a few years after the first survey, conducted in 2002. For
      the 2002 survey, respondents were 60,000 women, 22,759 of whom were aged 14-59
      years. For the 2006 survey, the sample consisted of 25,000 women aged 16-70
      years. Owing to the sensitivity of the issues, the telephone survey technique
      seems best suited because it provides more anonymity and guarantee of protection.
      The survey showed that the phenomenon of violence against women is most commonly
      perpetrated by the partner or ex-partner, even in cases of homicide. A comparison
      of the Italian data with those of the U.S.A. for the period 2001-2006 showed a
      specificity of Intimate Partner Violence in Italy, that seems to be related to
      cultural elements and psychologic and psychopathologic factors.

PMID- 24745085
TI  - Stability of morphine, codeine, and 6-acetylmorphine in blood at different
      sampling and storage conditions.
AB  - The stability of drugs in biological specimens is a major concern during the
      evaluation of the toxicological results. The stability of morphine, codeine, and
      6-acetyl-morphine in blood was studied after different sampling conditions: (i)
      in glass, polypropylene or polystyrene tubes, (ii) with addition of dipotassium
      ethylene diamine tetraacetic acid (K2EDTA) or sodium oxalate (Na2C2O4), and (iii)
      with or without the addition of sodium fluoride (NaF). Spiked blood samples were
      stored at two different temperatures (4 and -20 degrees C), analyzed after
      different storage times and after three freeze-thaw cycles. Opiate concentrations
      were decreased in all conditions, but the most unstable was 6-acetyl-morphine.
      The addition of NaF as preservative improved the stability of opiates at all
      conditions studied, whereas the type of anticoagulant did not affect the
      stability of opiates. It was concluded that blood samples should be stored at -20
      degrees C in glass tubes containing oxalate and NaF for maximum stability.

PMID- 24745086
TI  - Discounting of delayed and probabilistic losses over a wide range of amounts.
AB  - The present study examined delay and probability discounting of hypothetical
      monetary losses over a wide range of amounts (from $20 to $500,000) in order to
      determine how amount affects the parameters of the hyperboloid discounting
      function. In separate conditions, college students chose between immediate
      payments and larger, delayed payments and between certain payments and larger,
      probabilistic payments. The hyperboloid function accurately described both types
      of discounting, and amount of loss had little or no systematic effect on the
      degree of discounting. Importantly, the amount of loss also had little systematic
      effect on either the rate parameter or the exponent of the delay and probability
      discounting functions. The finding that the parameters of the hyperboloid
      function remain relatively constant across a wide range of amounts of delayed and
      probabilistic loss stands in contrast to the robust amount effects observed with
      delayed and probabilistic rewards. At the individual level, the degree to which
      delayed losses were discounted was uncorrelated with the degree to which
      probabilistic losses were discounted, and delay and probability loaded on two
      separate factors, similar to what is observed with delayed and probabilistic
      rewards. Taken together, these findings argue that although delay and probability
      discounting involve fundamentally different decision-making mechanisms,
      nevertheless the discounting of delayed and probabilistic losses share an
      insensitivity to amount that distinguishes it from the discounting of delayed and
      probabilistic gains.

PMID- 24745087
TI  - Internal mammary perforator vessels as recipient site for microsurgical breast
      reconstruction: a comparative histomorphometric analysis and incidence of
      degenerative vascular changes.
AB  - BACKGROUND: In microsurgical breast reconstruction, an adequate selection of
      recipient vessels is crucial for a successful outcome. Although the internal
      mammary (IM) vessels offer an attractive option, the internal mammary perforator
      (IMP) vessels are becoming a reliable alternative. The purpose of this study is
      to investigate the external diameters, lumen area, and atherosclerotic lesions
      changes of the IMP, IM, and deep inferior epigastric (DIE) vessels through
      quantitative and qualitative histomorphometric analysis. METHODS: Ninety-six
      vessels of bilateral IM, IMP, and DIE vessels from 16 fresh female cadavers were
      evaluated. Mean age was 54.06 +/- 5.7 years. External diameters, lumen area, and
      degenerative changes of the tunica intimae and media were analyzed by qualitative
      histomorphometric analysis. RESULTS: Seventy-one vessels (20 IM, 31 IMP, and 20
      DIE vessels) were included in the final histological analysis. A statistically
      lower external diameters and lumen area were presented by the IMP. The DIE
      vessels showed a lower incidence (10%) of moderate and severe intimal layer
      degenerative changes (P = 0.0589). The IMP and DIE vessels showed a lower
      incidence (9.4 and 25%, respectively) of major media layer degenerative changes
      (P = 0.0001). No major arterial degenerative lesions were observed in the IMP
      arteries. CONCLUSION: Although the IMP external diameters and lumen area were
      lower than the IM, the results of this study indicated that the tunica media
      layer in the IMP is less damaged than the other recipient vessels. The results of
      the comparative histological study permitted to describe additional advantages
      and disadvantages of using IMP as a recipient vessel for free flap breast
      reconstruction.

PMID- 24745088
TI  - Continuous high-dose vasopressors in free anterolateral thigh flap transfer for
      pharyngeal reconstruction: a report of two cases.
AB  - Use of vasopressors is controversial in patients undergoing free flap
      reconstruction. Recent literature has suggested that it is safe to administer
      vasopressors intraoperatively during these procedures. However studies have not
      addressed whether this safety extends to continuous high dose use. We present two
      cases of patients who underwent surgery for squamous cell carcinoma of the
      pharyngeal region, requiring laryngopharyngectomy. Both had pharyngeal
      reconstruction with a free anterolateral thigh (ALT) flap. The first required
      intraoperative vasopressors throughout the surgery, extending into the
      postoperative period. The second required vasopressors in the postoperative
      period continuously for weeks after surgery. Vasopressors were administered at
      treatment levels for shock. Neither developed flap compromise, suggesting that
      pharyngeal reconstruction with an ALT flap may be safely performed in the setting
      of continuous high-dose vasopressors.

PMID- 24745089
TI  - Carpal bone fractures in distal radial fractures: is computed tomography
      expedient?--reply.

PMID- 24745090
TI  - Potential contribution of mobilized circulating endothelial progenitor cells to
      development of retinal neovascularization in preterm infants with ROP.
AB  - PURPOSE: To investigate the role of endothelial progenitor cells in the
      pathogenesis of abnormal blood vessel formation in preterm infants with
      retinopathy of prematurity. MATERIAL AND METHODS: A total of 29 preterm infants
      with proliferative stage of retinopathy of prematurity and neovascularizatio
      (grade 3 or higher) were involved in this study. The CD133+/CD34+/CD144+ EPC
      count in peripheral blood was measured b flow cytometry. Plasma levels of stromal
      derived factor-1 (SDF-1), vascular endothelial growth factor, and insulin-like
      growth factor-1 (IGF-1) were quantified by enzyme-linked immunosorbent assay
      (ELISA). All cellular and biochemical measurements were performed twice in the
      same neonate: i) initially, during the proliferative phase of ROP, and ii)
      subsequently, during the remission after a successful retinal photocoagulation
      and regression of pathological blood vessels. RESULTS: The endothelial progenitor
      cells count significantly decreased during the remission phase, compared to the
      proliferative phase of retinopathy of prematurity in the same neonates. The SDF-1
      plasma level was found to be markedly lower during the remission stage and
      positively correlated with the endothelial progenitor cell count in peripheral
      blood. CONCLUSIONS: The endothelial progenitor cell count in peripheral blood of
      preterm infants significantly decreased with the regression of abnormal
      vasculature in the neonate retina. This may indicate that pathological blood
      vessel formation during the proliferative phase of retinopathy of prematurity
      results not only from local endothelial proliferation but also from the systemic
      endothelial progenitor cell mobilization.

PMID- 24745092
TI  - [Surgeons, have a think about!].

PMID- 24745091
TI  - Proceed with caution. The human gut microbiota, an attractive target for
      therapeutic interventions.

PMID- 24745093
TI  - [Quo vadis patient safety in Germany].

PMID- 24745094
TI  - [Letter to Christian Weymayr: "Scientability - a concept for the handling of
      homeopathic remedies by ebm. Z. Evid. Fortbild. Qual. Gesundh.wesen (ZEFQ) (2013)
      107, 606-610].

PMID- 24745095
TI  - [Letter to Christian Weymayr: "Scientability - a concept for the handling of
      homeopathic remedies by ebm. Z. Evid. Fortbild. Qual. Gesundh.wesen (ZEFQ) (2013)
      107, 606-610].

PMID- 24745096
TI  - [Letter to Christian Weymayr: "Scientability - a concept for the handling of
      homeopathic remedies by ebm. Z. Evid. Fortbild. Qual. Gesundh.wesen (ZEFQ) (2013)
      107, 606-610].

PMID- 24745097
TI  - [Letter to Christian Weymayr: "Scientability - a concept for the handling of
      homeopathic remedies by ebm. Z. Evid. Fortbild. Qual. Gesundh.wesen (ZEFQ) (2013)
      107, 606-610].

PMID- 24745098
TI  - [Letter to Christian Weymayr: "Scientability - a concept for the handling of
      homeopathic remedies by ebm. Z. Evid. Fortbild. Qual. Gesundh.wesen (ZEFQ) (2013)
      107, 606-610].

PMID- 24745099
TI  - [Answer to the letters of Fischer, Linde, Mattes, Hubner und Raspe].

PMID- 24745101
TI  - Providing health care coverage for former inmates.
AB  - (1) Prisoners have a higher prevalence of behavioral health disorders and chronic
      and infectious disease than the general population. (2) Suspending, rather than
      terminating, an inmate's Medicaid eligibility during incarceration helps
      facilitate coverage upon parole. (3) Policymakers are working to connect former
      inmates to coverage as a way to increase access to needed health services,
      decrease admissions to hospitals and emergency rooms, and reduce recidivism.

PMID- 24745102
TI  - Visual gut punch: persuasion, emotion, and the constitutional meaning of graphic
      disclosure.
AB  - The ability of government to "nudge" with information mandates, or merely to
      inform consumers of risks, is circumscribed by First Amendment interests that
      have been poorly articulated. New graphic cigarette warning labels supplied
      courts with the first opportunity to assess the informational interests attending
      novel forms of product disclosures. The D.C. Circuit enjoined them as
      unconstitutional, compelled by a narrative that the graphic labels converted
      government from objective informer to ideological persuader, shouting its warning
      to manipulate consumer decisions. This interpretation will leave little room for
      graphic disclosure and is already being used to challenge textual disclosure
      requirements (such as county-of-origin labeling) as unconstitutional. Graphic
      warning and the increasing reliance on regulation-by-disclosure present new free
      speech quandaries related to consumer autonomy, state normativity, and speaker
      liberty. This Article examines the distinct goals of product disclosure
      requirements and how those goals may serve to vindicate, or to frustrate,
      listener interests. I argue that many disclosures, and especially warnings, are
      necessarily both normative and informative, expressing value along with fact. It
      is not the existence of a norm that raises constitutional concern but rather the
      insistence on a controversial norm. Turning to the means of disclosure, this
      Article examines how emotional and graphic communication might change the
      constitutional calculus. Using autonomy theory and the communications research on
      speech processing, I conclude that disclosures do not bypass reason simply by
      reaching for the heart. If large graphic labels are unconstitutional, it will be
      because of undue burden on the speaker, not because they are emotionally
      powerful. This Article makes the following distinct contributions to the
      compelled commercial speech literature: critiques the leading precedent, Zauderer
      v. Office of Disciplinary Counsel, from a consumer autonomy standpoint; brings to
      bear empirical communications research on questions of facticity and rationality
      in emotional and graphic communications; and teases apart and distinguishes among
      various free speech dangers and contributions of commercial disclosure mandates
      with a view towards informing policy, law, and research.

PMID- 24745103
TI  - Questions, answers, and decontextualized rationality.

PMID- 24745104
TI  - The evolution of the education of deaf and hard of hearing children into speech
      language pathology, educational audiology, and special education.

PMID- 24745105
TI  - Technology intervention research with deaf and hard of hearing learners: levels
      of evidence.
AB  - The authors evaluated the research base relative to technology use with deaf and
      hard of hearing students, examining 29 peer-reviewed studies published January
      2000-August 2013 that used technology-based intervention (multimedia
      instructional applications/software) and investigating its effects on academic
      variables (academic skills used in instructional settings). They then evaluated
      the studies according to quality indicators for evidence-based research, both
      individually and as a body of evidence supporting intervention for deaf and hard
      of hearing students (Gersten et al., 2005; Horner et al., 2005; Institute of
      Education Sciences, 2013; Kratochwill et al., 2010, 2013). One of 24 group design
      studies met all Essential Quality Indicators; 3 of 5 single-case design studies
      did (Horner et al., 2005). No reviewed technology intervention met criteria for
      an established evidence base. Interventions are presented across technology types
      and academic areas to facilitate discussion of implications for researchers and
      practitioners.

PMID- 24745106
TI  - Deaf and hard of hearing students' through-the-air english skills: a review of
      formal assessments.
AB  - Strong correlations exist between signed and/or spoken English and the literacy
      skills of deaf and hard of hearing students. Assessments that are both valid and
      reliable are key for researchers and practitioners investigating the signed
      and/or spoken English skills of signing populations. The authors conducted a
      literature review to explore which tests researchers are currently using, how
      they administer the tests, and how reliability and validity are maintained. It
      was found that, overall, researchers working with this population use the same
      tests of English employed by practitioners working with hearing students (i.e.,
      the Peabody Picture Vocabulary Test, Expressive One-Word Picture Vocabulary Test,
      and Clinical Evaluation of Language Fundamentals). There is a disconnect between
      what is being used in research with deaf and hard of hearing students and what is
      being used in practice with them. Implications for practice are discussed.

PMID- 24745107
TI  - A comparison of phonemic and phonological awareness in educators working with
      children who are d/Deaf or hard of hearing.
AB  - The researchers explored the phonological awareness (PA) competency and
      confidence of educators working with children who are d/Deaf or hard of hearing.
      Performance comparisons were made between the two surveyed professional groups,
      teachers of the deaf (TODs; n = 58) and speech-language pathologists (SLPs; n =
      51). It was found that both respondent groups demonstrated gaps in PA knowledge
      and skills; however, SLPs performed significantly better, on average, than TODs.
      The educators expressed feelings of moderate confidence in their skills related
      to teaching children with hearing loss and assessing their PA. Correlations
      between educator demographics or levels of confidence and educator performance on
      PA measures did not yield significant findings. The results underscore the need
      for improved personnel preparation and PA continuing education for educators
      supporting literacy education of children who are d/Deaf or hard of hearing.

PMID- 24745108
TI  - Rate of language growth in children with hearing loss in an auditory-verbal early
      intervention program.
AB  - This longitudinal study explored the rate of language growth of children in an
      early intervention program providing auditory-verbal therapy. A retrospective
      investigation, the study applied a linear growth model to estimate a mean growth
      curve and the extent of individual variation in language performance on the
      Preschool Language Scale, 4th ed. (PLS-4; Zimmerman, Steiner, & Pond, 2002) for
      24 children with hearing loss in a convenience sample. A statistically
      significant change in raw scores was observed across 6-month intervals. However,
      growth in standard scores did not show statistically significant predictable
      change across the 6-month intervals. Scores on the language measure were closer
      to expectations for younger peers with normal hearing when compared to data
      reported for the PLS-4 normative sample. Language outcomes varied significantly
      for individual children based on time spent in early intervention, suggesting
      that intervention was contributing to growth.

PMID- 24745109
TI  - Using functional assessment to treat behavior problems of deaf and hard of
      hearing children diagnosed with autism spectrum disorder.
AB  - A defining feature of autism spectrum disorders is atypical behaviors, e.g.,
      stereotypy, noncompliance, rituals, and aggression. Deaf and hard of hearing
      individuals with autism present a greater challenge because of additional issues
      related to their hearing status. One conceptualization of problem behavior is
      that it serves a communication function, i.e., the person has learned that
      certain misbehaviors may be reinforced in some way. The present article describes
      "functional behavior assessment," a group of state-of-the-art methodologies that
      allow a caregiver to determine the cause of the behavior, so that treatment-
      based on that cause--will be more effective. Different methods of functional
      assessment are described, along with a step-by-step implementation sequence. The
      results of a functional assessment should lead to more effective programming,
      resulting in quicker elimination of the behavioral concerns, and allow the person
      to gain access to greater independence and more reinforcement.

PMID- 24745110
TI  - [Old age and risks].

PMID- 24745111
TI  - [The end of life of the elderly].

PMID- 24745112
TI  - [Optimal medication dosage in nursing homes].

PMID- 24745113
TI  - [Promoting a culture of well-treatment in nursing homes].
AB  - The notion of well-treatment has followed on from the prevention of maltreatment,
      resulting from a discussion process instigated by the managers of nursing homes
      and from actions deployed over the years. After the designation of a lead person,
      the formalisation of reference documents to be used by the staff, and the
      assessment of monitoring indicators, professionals were invited to consider their
      professional practices. This article presents the results of this approach in
      Angouleme.

PMID- 24745114
TI  - [A support group for Alzheimer's patients in a day care center].
AB  - A support group for Alzheimer's patients in a day care centre is an innovative
      concept. A place of listening and exchanges, it gives participants an opportunity
      to speak and helps them form a positive image of themselves.This scheme is
      supported by an ethical approach which consists in interacting with the person
      away from the confines of the stigmatising representations associated with
      Alzheimer's disease.

PMID- 24745115
TI  - [Must we choose between "cure" and "care"?].
AB  - In long-term care units, the most adapted caregiving model is that of "cure". The
      caregiver-patient relationship is approached exclusively through the nursing
      procedure. Unlike the "care" model which approaches this relationship outside the
      nursing activity itself, the "cure" model can be transformed to integrate this
      human dimension.

PMID- 24745116
TI  - [Continuing professional development in nursing homes].
AB  - Continuing professional development (CPD) is obligatory for healthcare
      professionals. A CPD programme must combine the analysis of professional
      practices with cognitive elements. The opportunity to evaluate existing practices
      in a nursing home is important.

PMID- 24745117
TI  - [The elderly and alcohol, an unrecognized problem].

PMID- 24745118
TI  - [Aging and alcohol consumption].
AB  - The risks associated with the consumption of alcohol are higher in old age. These
      risks are somatic, psychological or related to addiction and negative
      interactions between alcohol and medication. The misuse of alcohol does not
      disappear with age, but it takes different forms, sometimes atypical, depending
      on the co-morbidities, the circumstances and the living or care environment.
      Treatment is always possible, even in elderly people, with certain specificities,
      but also with a prognosis which is as good as if not better than in younger
      adults.

PMID- 24745119
TI  - [Alcohol in care homes for the elderly].
AB  - The majority of those living in care homes for the elderly are very old, with
      multiple pathologies and taking multiple forms of medication. They are therefore
      more fragile and vulnerable in the face of alcohol, both with occasional
      consumption or with addictive behaviour. Far from anecdotal, these situations
      arise almost on a daily basis for the frontline caregivers. They are sometimes
      difficult to detect by other professionals who do not have such prolonged contact
      with the residents. Addressing the risk as well as the misuse of alcohol in a
      nursing home is a matter for the whole institute and must involve all the
      players, professionals, families and residents, in a cross-disciplinary and
      coherent approach. Addiction treatment, in the particular case of nursing home
      residents, as for the general population, considers all methods of consumption
      and actions, from prevention to the reduction of risks or harmful effects, to
      curative treatment, including alcohol withdrawal.

PMID- 24745120
TI  - [Nutritional care of elderly people with chronic alcoholism].
AB  - The management of elderly people with chronic alcoholism involves several
      players, including dieticians.Without stigmatisingthe person or apportioning
      blame, the challenge is to enable them to become a player in their treatment.
      Long-term support is required.

PMID- 24745121
TI  - [Home aides and families faced with alcoholic behavior in elderly people].
AB  - Alcoholic behaviour in elderly people living at home leads to the establishment
      of a singular relationship between the family and the home helpers. The
      professionals have a special role within the family system but one which at the
      same time is, paradoxically, limited. The intervention of a third party, in the
      framework of an alcoholism support network, can help to avoid the breakdown of
      the care within the home as a result of the mental exhaustion of the various
      players, as well as the occurrence of conflicts within the family circle in the
      home.

PMID- 24745122
TI  - [Bibliography. Alcoholism in the elderly].

PMID- 24745123
TI  - [Oxygen therapy: advantages and inconveniences].

PMID- 24745124
TI  - [The main drug interactions in gerontology].

PMID- 24745125
TI  - Correlation between the spatial distribution of leprosy and socioeconomic
      indicators in the city of Vitoria, State of ES, Brazil.
AB  - INTRODUCTION: Leprosy is a disease that is directly linked to poverty. The number
      of cases in Vit6ria, the capital city of Espirito Santo, has been decreasing in
      recent years, but the disease remains highly endemic. This research aimed to
      identify relationships between the epidemiological status of leprosy and
      socioeconomic indicators during the period from 2005 to 2009. METHODS: An
      ecological study was performed based on the spatial distribution of leprosy in
      Vit6ria, Espirito Santo, between 2005 and 2009. The source data used were records
      available at the Secretary of State for Health of the Espirito Santo. We used the
      Urban Quality Index (IQU) as the leprosy-associated socioeconomic variable. The
      data were analysed with covariate and spatial effects by the WinBugs programme
      (Version 1.4) and R (Version 2.12). RESULTS: The spatial distribution of leprosy
      in the district is not uniform. By studying the geographic distribution of
      leprosy cases, and the risks estimated by the complete Bayesian model, it was
      possible to gain further insight into the distribution of leprosy cases. It was
      noted that neighbourhoods with a low IQU have a higher leprosy case detection
      rate than neighbourhoods with a higher IQU. This result reinforced the theory
      that a low IQU is associated with the emergence of leprosy. CONCLUSION: The model
      methodology adopted enabled the verification of the effect of the influence of
      covariates related to the social determinants of health as well as the spatial
      structure, in contrast to the gross rate method that does not aggregate this
      information. The results obtained suggest that leprosy control may be promoted by
      improving the socioeconomic indicators of neighbourhoods, and highlights the need
      for implementation of health policies aimed at people who live in areas where
      they are at greatest risk of getting sick.

PMID- 24745126
TI  - Combining peer-led self-care interventions for people affected by leprosy or
      diabetes in leprosy-endemic countries. What do health care professionals think?
AB  - INTRODUCTION: Leprosy is slowly decreasing in incidence whereas diabetes is a
      growing health concern. Despite differences in aetiology, both diseases may lead
      to peripheral neuropathy and subsequent injuries and permanent impairments. There
      are also indications of similarities in psychosocial consequences. Prevention of
      Disability (POD) and self-management are often recommended for both diseases.
      This led to the idea of exploring the feasibility of combined peer-led self-care
      interventions for people with these disorders. OBJECTIVE: To explore the opinions
      of health care professionals about combining peer-led self-care interventions for
      people affected by leprosy or diabetes in leprosy-endemic countries. METHOD: An
      exploratory study was conducted to collect quantitative data by means of an e
      questionnaire and qualitative data through in-depth semi-structured interviews
      with key informants. RESULTS: In total, 227 respondents answered the e
      questionnaire and 22 in-depth interviews were conducted. Resemblances in physical
      complications between leprosy and diabetes were confirmed by the respondents.
      Psychosocial similarities included limitations in daily activity and in social
      participation, but stigma in leprosy was thought to be an important difference.
      Considerable overlap in current practices was found, mainly in patient education
      in POD, skin assessment and skin care, and the recommendation to use protective
      footwear. Knowledge exchange between leprosy and diabetes specialists is limited,
      although combined interventions were reported. The majority of respondents think
      that combined interventions are 'possible' (33.3%) or 'possible and promising'
      (30.8%). Professionals working with both diseases are more positive than those
      working with leprosy or diabetes only. The greatest barriers for combined
      interventions are perceived to be leprosy-related stigma, differences in
      underlying socio-economic status, attitudes of health care professionals and the
      current organization of health care systems. CONCLUSIONS: Responses indicate
      perspectives for combined interventions for the prevention of disabilities. For
      this, it is essential to intensify knowledge exchange between leprosy and
      diabetes professionals, to overcome barriers and to secure government policy
      support. Opportunities should be assessed in a situation-specific way.

PMID- 24745127
TI  - Self-care groups of leprosy-affected people in Mozambique.
AB  - INTRODUCTION: In 2011, the national leprosy control programme in Mozambique
      decided to promote the setting up of self-care groups (SCGs) for prevention and
      care of disabilities. OBJECTIVES: To present an overview of the national SCG
      strategy and to understand the perceptions of people with leprosy regarding the
      benefits and challenges of participating in the SCGs in Mozambique. METHODS: Semi
      structured group interviews were carried out with 22 SCGs involving 299 leprosy
      affected people in Nampula and Manica provinces. RESULTS: SCGs are involved in
      different activities and do not limit themselves to activities related to
      disability care. The majority of respondents expressed satisfaction about their
      participation in SCGs. Apart from perceived benefits in relation to their
      disabilities, the majority of SCG members also reported benefits in social
      participation. Lack of training, insufficient resources for income generation and
      long distances were the major challenges for SCGs, especially in the Manica
      province. CONCLUSIONS: People affected with leprosy perceive SCGs as useful in
      self-care for prevention of disabilities and social participation.

PMID- 24745128
TI  - The quality of life of people with leprosy-related residual impairment and
      disability in Malawi--is there a difference between people living in a
      leprosarium and those re-integrated into their communities?
AB  - INTRODUCTION: To compare the quality of life of people affected by leprosy living
      in a leprosarium and those reintegrated in communities in the southern region of
      Malawi. DESIGN: A translated version of the World Health Organization Quality of
      Life BREF questionnaire (WHOQOL-BREF) was administered among two groups of people
      with leprosy-related residual impairment and disability living in either a
      leprosarium (male 47, female 53) or re-integrated into communities (male 41,
      female 57). The cross-sectional quantitative survey was conducted by trained
      Leprosy Control Assistants (LCAs). Descriptive statistics of mean and standard
      deviation were used to summarise the data while differences between the groups
      were evaluated using independent t-test. Level of significance was set at P <
      0.05. RESULTS: Demographic data revealed that there were more residents of an
      older age in the leprosarium. There was no statistically significant differences
      in the WHOQOL-BREF mean scores between by those affected by leprosy living in the
      two contexts. Statistically significant differences existed in the psychological,
      physical and environmental domains when age and gender were used as confounding
      factors. CONCLUSIONS: We conclude that there is need to provide interventions
      that will encompass age and gender to all those affected by leprosy to improve
      their quality of life in both contexts.

PMID- 24745129
TI  - Superposition of leprosy and other neglected tropical diseases in the state of
      Rio de Janeiro: a case series report.
AB  - This is a report on eight non-HIV infected leprosy patients presenting unusual co
      infection with other, often neglected, tropical diseases, namely: American
      tegumentary leishmaniasis (ATL), sporotrichosis, and cryptococcosis. To the best
      of our knowledge, there have been very few ATL-leprosy co-infection reports in
      the literature to date and only one previous description of the coexistence of
      leprosy-cryptococcosis and leprosy-sporotricosis.

PMID- 24745130
TI  - Country profile: leprosy in Brazil.
AB  - Brazil has high rates of leprosy case detection, especially in the northern and
      west-central areas of the country. Effective decentralisation of routine
      treatment for leprosy has gathered pace since the year 2000 and this has improved
      access for patients, leading to a peak in new case detection in 2003 and a
      gradual decline thereafter. This is in parallel with specific government
      programmes aimed at poverty reduction. Disability prevention and surveillance for
      drug resistance remain important tasks within the leprosy control programme, in
      which six key referral centres lead the way.

PMID- 24745131
TI  - Optic nerve involvement in a borderline lepromatous leprosy patient on multidrug
      therapy.
AB  - Amidst the plethora of ocular complications of leprosy, involvement of the
      posterior segment or optic nerve is extremely rare. The mechanism of optic
      neuritis in leprosy is poorly understood. A 47 year-old man presented with a
      single lesion suggestive of mid-borderline (BB) leprosy over left periorbital
      region; the histology showed borderline lepromatous (BL) leprosy with a BI of 3+.
      After initial improvement with WHO MDT-MB and prednisolone (40 mg/d) he developed
      sudden and painless diminished vision in the left eye, about 3 weeks later. His
      visual acuity was 6/9 in the left and 6/6 in the right eye, and there was left
      optic disc edema, hyperemia and blurred disc margins. Treatment with prednisolone
      (60 mg/d) along with WHO MDT-MB continued. A month later he returned with
      painless diminished vision in the other eye as well. Visual acuity was 6/6 in the
      right and 6/12 in the left eye, and there was right optic disc edema and left
      optic disc atrophy. CT of the head and MRI of the brain were normal. Inflammatory
      edema of the orbital connective tissue or other surrounding structures, or direct
      infiltration of vasa nervosa with resultant vascular occlusion leading to optic
      nerve ischemia, seems the most plausible explanation of optic nerve involvement
      in this case.

PMID- 24745132
TI  - Mistreatment of immigrants: the history of leprosy in Canada.

PMID- 24745133
TI  - Changing services means understanding them.

PMID- 24745134
TI  - Insights into physician scheduling: a case study of public hospital departments
      in Sweden.
AB  - PURPOSE: The purpose of this paper is to describe current physician scheduling
      and concomitant opportunities for improvement in public hospital departments in
      Sweden. DESIGN/METHODOLOGY/APPROACH: A total of 13 departments spread
      geographically across Sweden covering seven different specialties participated in
      the study. Data were collected through interviews with individuals involved in
      creating physician schedules. All departments investigated provided copies of the
      documents necessary for physician scheduling. FINDINGS: Physician scheduling
      required the temporal coordination of patients, physicians, non-physician staff,
      rooms and equipment. A six-step process for creating physician schedules could be
      distinguished: capacity and demand overview, demand goal and schedule setting,
      vacation and leave requests, schedule creation, schedule revision, and schedule
      execution. Several opportunities for improvement could be outlined; e.g.
      overreliance on memory, lacking coordination of resources, and redundant data
      entering. RESEARCH LIMITATIONS/IMPLICATIONS: The paucity of previous studies on
      physician scheduling lends an exploratory character to this study and calls for a
      more thorough evaluation of the feasibility and effects of the approaches
      proposed. The study excluded the scheduling of non-physician staff. PRACTICAL
      IMPLICATIONS: To improve physician scheduling and enable timeliness, three
      approaches are proposed: reinforcing centralisation, creating learning
      opportunities, and improving integration. ORIGINALITY/VALUE: This paper is among
      the few to investigate physician scheduling, which is essential for delivering
      high quality care, particularly concerning timeliness. Several opportunities for
      improvement identified in this study are not exclusive to physician scheduling
      but are pervasive in healthcare processes in general.

PMID- 24745135
TI  - Reporting adverse events at geriatric facilities: categorization by type of
      adverse event and function of reporting personnel.
AB  - PURPOSE: Adverse events and patient care-related adverse events are a challenging
      universal problem, among elder residents of geriatric facilities. The aim of this
      study was to examine which types of adverse events are characteristic of the
      geriatric center studied and which of the nursing staff reported this event.
      DESIGN/METHODOLOGY/APPROACH: Data were retrieved from the computerized adverse
      event management system at a large geriatric center in central Israel, and all
      adverse events reported over the past three years were examined. FINDINGS: The
      study findings indicate that the most common type of adverse event was falls.
      Older nurses with greater seniority in the facility show a higher tendency to
      report adverse events. In addition, registered nurses were found to report more
      often than practical nurses. PRACTICAL IMPLICATIONS: This study highlights the
      important role that nurses can play in reporting and reducing adverse events. The
      role of the nurse is becoming increasingly complex, especially in geriatric
      facilities, which serve people with complex mental and physical states who are
      more susceptible to adverse events to begin with. ORIGINALITY/VALUE: Despite the
      large number of adverse events, few studies have been undertaken on adverse
      events in geriatrics in general, and in nursing homes and long-term facilities in
      particular. Answers to these questions will enable improvement in the quality of
      care provided and ensure a safe care environment for residents. Systematically
      examining types of adverse events and the characteristics of those who do and do
      not report them, can contribute to improvement of processes in the healthcare
      system in general, and in the facility in particular. Additionally, efficient
      investigation can improve the behavior of those who enable adverse events.

PMID- 24745136
TI  - Error rates in physician dictation: quality assurance and medical record
      production.
AB  - PURPOSE: The purpose of the paper is to determine the instance of errors made in
      physician dictation of medical records. DESIGN/METHODOLOGY/APPROACH: Purposive
      sampling method was employed to select medical transcriptionists (MTs) as
      "experts" to identify the frequency and types of medical errors in dictation
      files. Seventy-nine MTs examined 2,391 dictation files during one standard work
      day, and used a common template to record errors. FINDINGS: The results
      demonstrated that on the average, on the order of 315,000 errors in one million
      dictations were surfaced. This shows that medical errors occur in dictation, and
      quality assurance measures are needed in dealing with those errors. RESEARCH
      LIMITATIONS/IMPLICATIONS: There was no potential for inter-coder reliability and
      confirming the error codes assigned by individual MTs. This study only examined
      the presence of errors in the dictation-transcription model. Finally, the project
      was done with the cooperation of MTSOs and transcription industry organizations.
      PRACTICAL IMPLICATIONS: Anecdotal evidence points to the belief that records
      created directly by physicians alone will have fewer errors and thus be more
      accurate. This research demonstrates this is not necessarily the case when it
      comes to physician dictation. As a result, the place of quality assurance in the
      medical record production workflow needs to be carefully considered before
      implementing a "once-and-done" (i.e. physician-based) model of record creation.
      ORIGINALITY/VALUE: No other research has been published on the presence of errors
      or classification of errors in physician dictation. The paper questions the
      assumption that direct physician creation of medical records in the absence of
      secondary QA processes will result in higher quality documentation and fewer
      medical errors.

PMID- 24745137
TI  - The hospital survey on patient safety culture in Portuguese hospitals: instrument
      validity and reliability.
AB  - PURPOSE: Quantitative instruments to assess patient safety culture have been
      developed recently and a few review articles have been published. Measuring
      safety culture enables healthcare managers and staff to improve safety behaviours
      and outcomes for patients and staff. The study aims to determine the AHRQ
      Hospital Survey on Patient Safety Culture (HSPSC) Portuguese version's validity
      and reliability. DESIGN/METHODOLOGY/APPROACH: A missing-value analysis and item
      analysis was performed to identify problematic items. Reliability analysis, inter
      item correlations and inter-scale correlations were done to check internal
      consistency, composite scores. Inter-correlations were examined to assess
      construct validity. A confirmatory factor analysis was performed to investigate
      the observed data's fit to the dimensional structure proposed in the AHRQ HSPSC
      Portuguese version. To analyse differences between hospitals concerning
      composites scores, an ANOVA analysis and multiple comparisons were done.
      FINDINGS: Eight of 12 dimensions had Cronbach's alphas higher than 0.7. The
      instrument as a whole achieved a high Cronbach's alpha (0.91). Inter-correlations
      showed that there is no dimension with redundant items, however dimension 10
      increased its internal consistency when one item is removed. ORIGINALITY/VALUE:
      This study is the first to evaluate an American patient safety culture survey
      using Portuguese data. The survey has satisfactory reliability and construct
      validity.

PMID- 24745138
TI  - Important quality aspects in the transfer process.
AB  - PURPOSE: Admission to and transfer from an intensive care unit affects not only
      the patient but also his or her relatives. The authors aimed to investigate
      relatives' perceptions of quality of care during a patient's transfer process
      from an intensive care unit to a general ward. DESIGN/METHODOLOGY/APPROACH: The
      study had a mixed method design that included quantitative data and answers to
      open questions. The participants were 65 relatives of patients who received care
      in an ICU. They were recruited from two hospitals in Sweden. FINDINGS: A majority
      perceived the transfer process as important, but analysis also showed that the
      participants rated it as an area for improvements. The relatives wanted
      participation, personal insight and control, respectful encounters, proximity,
      reassurance, continuous quality, reconnection and feedback. The relatives'
      participation in the transfer process was perceived as inadequate by 61 per cent,
      and the support that was received after the ICU discharge was perceived as
      inadequate by 53 per cent. The patients' length of stay in the ICU affected the
      relatives' perceptions of the quality of care. Overall, the relatives seemed to
      desire that the transfer process includes a continuous care, a competent staff,
      available information throughout the transfer process and personal involvement in
      the care, both before and after the transfer from the ICU. RESEARCH
      LIMITATIONS/IMPLICATIONS: The conclusion of this study is that relatives' needs
      and seeking for a well-planned ICU transitional process organisation with
      continuous quality before and after transfer, informational strategies that
      encourage the relatives to be involved and an organisation with competence
      throughout the healthcare chain are vital for quality. PRACTICAL IMPLICATIONS:
      The conclusion of this study is that relatives' needs and seeking for a well
      planned ICU transitional process organisation with continuous quality before and
      after transfer, informational strategies that encourage the relatives to be
      involved and an organisation with competence throughout the healthcare chain are
      vital for quality. ORIGINALITY/VALUE: The findings have important implications
      for nursing and nursing management. A relative's perception of the quality of
      care before and after transfer from ICU may be a valuable source to evaluate the
      ICU transitional care.

PMID- 24745139
TI  - European registry for quality improvement in cataract surgery.
AB  - PURPOSE: A project aimed at creating a multi-national database for cataract and
      refractive surgery was initiated in 2008. The database was intended for learning
      and clinical improvement, not supervision. The project was co-funded by the
      European Union, under the Executive Agency for Health and Consumers and the
      European Society of Cataract and Refractive Surgeons (ESCRS) and supported by 11
      national societies for cataract and refractive surgery. The purpose of this
      article is to describe the setup of the database and the ensuing achievements
      within cataract surgery after four years. DESIGN/METHODOLOGY/APPROACH: A web
      based system was created for input and output of data, with a software interface
      to two databases, one for cataract surgery and one for refractive surgery. Data
      can be put in either manually through web forms or by transfer of data from
      existing national registries or large electronic medical record systems. Output
      of reports from the system or export of one's own data is available on the web.
      The data are anonymous to all users, with the sole exception that reporting
      surgeons and clinics have access to their own data. The system does not include
      any patient identification. FINDINGS: After four years, data from 16 countries
      have been entered into the system, including reports of more than 900,000
      cataract extractions. The database has been used by individual clinics for
      benchmarking and clinical improvement work, and has also served as the basis for
      new clinical guidelines for cataract surgery. The ESCRS has guaranteed the
      sustainability of the database after the project period. ORIGINALITY/VALUE: A
      European quality registry with data input from surgeons and clinics in 16
      European countries has been established. Close to one million surgeries have been
      entered into the system during the first four years. Evidence-based guidelines
      have been published based on data in the registry. The system is used for
      benchmarking by both experienced surgeons and trainees.

PMID- 24745140
TI  - Patient choice of a hospital: implications for health policy and management.
AB  - PURPOSE: The purpose of this study was to identify the most important influencing
      factors in choosing a hospital by a patient. DESIGN/METHODOLOGY/APPROACH: This
      study involved a mixed research design. Focus groups and in-depth individual
      interviews were conducted with patients to explore reasons for choosing a
      hospital. In addition, this study involved survey-based research on the patient
      choice. FINDINGS: Type of the hospital, type of the service, word of mouth, cost
      of services, the health insurance programme, location, physical environment,
      facilities, providers' expertise and interpersonal behaviour, and reputation of
      the hospital influenced patients' choice of a hospital. Doctor recommendations
      and health insurance programme were the main reasons for choosing a hospital for
      inpatients and outpatients respectively. PRACTICAL IMPLICATIONS: Identifying and
      understanding key factors that influence a patient choice of a healthcare setting
      helps managers and policy makers invest their resources in those critical areas
      and improve those aspects of their services to attract more patients.
      ORIGINALITY/VALUE: This article contributes to healthcare theory and practice by
      developing a conceptual framework for understanding the factors that influence a
      patient choice of a healthcare setting.

PMID- 24745141
TI  - [A new plan to reduce cancer inequalities].

PMID- 24745142
TI  - Prolactin (PRL) and prolactin receptor (PRLR) genes and their role in poultry
      production traits.
AB  - Prolactin (PRL), secreted from the anterior pituitary, plays extensive roles in
      osmoregulation, corpus luteum formation, mammogenesis, lactogenesis,
      lactopoiesis, and production of crop milk. In birds, prolactin (PRL) is generally
      accepted as crucial to the onset and maintenance of broodiness. All the actions
      of prolactin (PRL) hormone are mediated by its receptor (PRLR), which plays an
      important role in the PRL signal transduction cascade. It has been well
      established that the PRL gene is closely associated to the onset and maintenance
      of broody behavior, and could be a genetic marker in breeding against broodiness
      in chickens. Meanwhile, the prolactin receptor (PRLR) gene is regarded as a
      candidate genetic marker for reproductive traits. PRLR is also an important
      regulator gene for cell growth and differentiation. The identified polymorphism
      of this gene is mainly viewed in terms of egg production traits. Due to different
      biological activities attributed to PRL and PRLR, they can be used as major
      candidate genes in molecular animal breeding programs. Characterization of PRL
      and PRLR genes helps to elucidate their roles in birds and provides insights into
      the regulatory mechanisms of PRL and PRLR expression conserved in birds and
      mammals.

PMID- 24745143
TI  - Bacterial translocation in alymphoplasia (aly/aly) mice.
AB  - Bacterial translocation (BTL) is defined as the passage of viable bacteria from
      the gastrointestinal tract to the organs. This study was to elucidate the roles
      of Peyer's patches (PPs) and/or mesenteric lymph nodes (MLNs) in BTL.
      Alymphoplastic mutant mice and phenotypically normal heterozygous micewere
      dominantly colonized with streptomycin-resistant Escherichia coli and BTL was
      examined. In PP- and MLN-competent mice, BTL to MLNs was detected in 100% of
      mice, but BTL to organs was rare (25%). On the other hand, in PP- and MLN
      deficientmice, BTL to organs was detected in 91% of mice. The results clearly
      indicate that PPs are not the only site for bacterial entry.

PMID- 24745144
TI  - New stands of species of the Paramecium aurelia complex (Ciliophora, Protozoa) in
      Europe and South America (Ecuador).
AB  - The occurrence of species of the P. aurelia complex has been studied at a large
      scale in Europe and the majority of known species of the complex have been found
      there. However, a different number of habitats were studied in particular zones
      of Europe, the greatest number in the central zone. Herein new stands of several
      species of the Paramecium aurelia complex are presented from Europe including P.
      primaurelia, P. biaurelia, P. triaurelia, P. octaurelia, P. novaurelia, and P.
      dodecaurelia. In South America, studies concerning the distribution of the P.
      aurelia species complex were carried out only occasionally and the presence of
      some cosmopolitan species of the complex has been recorded, i.e. P. primaurelia,
      P. biaurelia, and P. tetraurelia. Recently, new stands of P. primaurelia and P.
      septaurelia were found in Ecuador. Ciliate biogeography and distribution is also
      discussed.

PMID- 24745145
TI  - Gene mapping as a method for verifying sequence localization based on
      interspecific chromosome painting (ZOO-FISH).
AB  - The results obtained in the present study made it possible to place selected
      markers on the physical map of the arctic fox genome. With the use of
      fluorescence in situ hybridization (FISH) the GHR (3q24) and 1110 (1q21.1-21.2)
      genes and the FH2537 (5q11.3) microsatellite were localized on arctic fox
      chromosomes. The results confirmed previously proposed homologies using the ZOO
      FISH technique, except for the 1110 gene. This suggests that the gene underwent a
      rearrangement (an inversion) that changed its localization compared to the dog.

PMID- 24745146
TI  - Crossbreeding effect on genome stability in pig (Sus scrofa scrofa).
AB  - Aneuploid cell percentages and frequencies of CAs and SCEs were investigated in
      10 Calabrian pigs, 10 LW pigs and 19 Calabrian x LW crossbred pigs, in order to
      compare genome stability between an autochthonous pig breed and a highly selected
      one and to verify if genome stability of their progeny, as other phenotypic
      traits, are influenced by heterosis. The mean number of cells per animal with
      structural aberrations, excluding gaps, was 6.20 +/- 2.39, 4.90 +/- 2.02 and 4.52
      +/- 3.34 in Calabrian, LW and crossbred pigs, respectively, while the mean number
      of total CAs without gaps was 0.14 +/- 0.38, 0.11 +/- 0.35 and 0.11 +/- 0.35,
      respectively. The mean number of SCEs was 7.30 +/- 3.24 in Calabrian pigs, 6.45
      +/- 2.74 in LW pigs and 6.28 +/- 2.90 in the crossbred ones. Percentages of cells
      with aneuploidy were 7.30, 10.10 and 10.79 in Calabrian, LW and crossbred pigs,
      respectively. In particular, the Calabrian breed showed higher values compared to
      LW in each test, however, there were statistically significant differences only
      in the mean number of SCEs per cell (P<0.01). In addition, there is a positive
      effect of crossbreeding on baseline levels of genome stability in the crossbred
      group that shows in all tests, excluding gaps, mean values of cellular or
      chromosome damage similar to the LW group.

PMID- 24745147
TI  - FASN gene polymorphism in indigenous cattle breeds of Turkey.
AB  - The aim of this study was to determine the variants of the thioesterase (TE) beta
      ketoacyl reductase (KR) domains of the Fatty Acid Synthase (FASN) gene, in the
      East Anatolian Red (EAR) and South Anatolian Red (SAR) cattle breeds. It has been
      suggested that the FASN gene is effective on fatty acid composition of meat in
      cattle. In this study, the genotype and allele frequencies of g.17924 A>G,
      g.18440 G>A and g.16024 G>A, g.16039 T>C in TE and KR domains, respectively, were
      detected by using polymerase chain reaction - restriction fragment length
      polymorphism (PCR-RFLP) method. The g.18663 T>C polymorphism of the TE domain was
      determined by direct sequencing. The GG genotype of the g.17924 A>G polymorphism,
      which affects unsaturated fatty acid composition positively, has a high frequency
      in EAR and SAR breeds. The frequencies of the two haplotypes g.16024 G>A and
      g.16039 T>C in the KR domain were found to be significantly high in both breeds.
      These haplotypes also have positive effects on unsaturated fatty acid
      composition. The AA genotype of the g. 18440 G>A polymorphism, which is suggested
      to be absent in Bos taurus breeds, was detected in SAR and EAR breeds with
      frequencies close to those in Bos indicus breeds. In conclusion, we suggest that
      SAR and EAR cattle breeds have an advantage in terms of genotype and haplotype
      distribution of the polymorphisms in TE and KR domains of the FASN gene.
      Additionally g.18440 G>A polymorphism might be a potential marker for breed
      discrimination.

PMID- 24745148
TI  - Genotyping of Anaplasma phagocytophilum strains from Poland for selected genes.
AB  - Anaplasma phagocytophilum is a veterinary and medical tick-borne pathogen of
      vertebrates which invades granulocytes. The potential reservoirs of Anaplasma
      include game animals and small mammals. The aim ofthis study was to gain insight
      into the variability ofnucleotide sequences of ribosomal and selected protein
      coding genes (ankA, msp4 and the groESL heat-shock protein operon) present in
      isolates of A. phagocytophilum collected from wild ruminants (Cervus elaphus and
      Capreolus capreolus) in Poland. Fragments of the genes were amplified using PCR
      and sequenced. High DNA variability was found in fragments of the msp4 and groESL
      genes (15 and 8 alleles, respectively), whereas ankA and 16S rRNA demonstrated
      very little or no variability (2 and 1 alleles, respectively). Unique allelic
      profiles were determined for the examined groups and allowed distinguishing 6 A.
      phagocytophilum genotypes, 2 of which were reported only in the roe deer (C.
      capreolus), and 1 in the red deer (C. elaphus).

PMID- 24745149
TI  - Karyotype and C-banding pattern of the domestic geese Anser anser populations
      (Aves: Anatidae) in Egypt.
AB  - The karyotype and C-banding pattern of domestic Greylag geese Anser anser anser
      populations collected from five localities in El Minia, Egypt, that have either
      whitish grey or white feather color patterns were described. All populations have
      a diploid number of 2n= 80 chromosomes. Of the 80 chromosomes, 10 pairs,
      including ZW chromosomes, were macrochromosomes and the remaining 30 pairs were
      microchromosomes. Slight variation in the size of macrochromosomes was observed
      amongst populations. However, obvious variation of C-banding distribution was
      found and attributed to variation of euchromatin content and its correlation with
      chromosome size and arrangement of constitutive heterochromatin. Nevertheless,
      significant variation in the mean number of C-heterochromatin blocks in
      microchromosomes was attributed to either transformation of heterochromatin into
      euchromatin and vice versa or to involvement of structural chromosomal
      aberrations during karyotype evolution. The present results show that A. anser
      populations common in Egypt could be distinguished from those of A. anser and A.
      cygnoides occurring elsewhere in Europe and Asiaviavariability in chromosome
      morphology of pairs nos. 2, 3 and 4.

PMID- 24745150
TI  - In vitro effects of quercetin on oxidative stress mediated in human erythrocytes
      by benzoic acid and citric acid.
AB  - Benzoic acid (BA) and citric acid (CA) are food additives commonly used in many
      food products. Food additives play an important role in food supply but they can
      cause various harmful effects. The in vitro adverse effects of BA and CA and the
      protective effect of quercetin on human erythrocytes were investigated by
      measuring malondialdehyde (MDA) levels and superoxide dismutase (SOD), catalase
      (CAT), glutathione peroxidase (GPx) and glutathione-S-transferase (GST)
      activities. Erythrocytes were incubated with BA and CA, at three doses of 50, 100
      and 200 microg/ml, and quercetin, at a concentration of 10 microM. After BA and
      CA application, a dose-dependent increase in MDA level and decreases in SOD, CAT,
      GST and GPx activities were found in erythrocytes. Among the two food additives,
      BA exerted a more harmful influence on human erythrocytes than CA. The protective
      effects of quercetin against oxidative stress--induction in the human
      erythrocytes by CA and BA, were found when these two food additives were applied
      at each of three doses of 50, 100 and 200 microg/ml. However, complete protection
      of quercetin against CA toxicity was only observed when this agent was applied at
      a lower dose of 50 microg/ml. Quercetin did not completely protect erythrocytes
      even at the lowest concentration of BA.

PMID- 24745151
TI  - Lack of TCRalphabeta+ CD8+ and TCRgammadelta+ lymphocytes ameliorates LPS induced
      orchitis in mice--preliminary histological observations.
AB  - The inflammation of the reproductive system can affect reproduction causing
      partial or complete infertility. It is well known that lipopolysaccharide (LPS)
      triggers an inflammatory response in the whole organism, including
      immunologically privileged organs, e.g. the testicles. Adult male TCRalpha-/-,
      TCRdelta-/-, CD1d-/- and beta2m-/- on B10.PL (H-2(u)) and B10.PL control mice
      were intraperitonealy (i.p.) injected with lipopolysaccharide (LPS). The animals
      were killed 24h and 10 days post LPS treatment and their gonads were prepared for
      microscopic examination. Histological changes in the testes after LPS injection
      were found only in control B10PL and CD1d-/- mice. The experiments revealed
      disturbances in Leydig's glands structure, blood vessel dilatation in the
      interstitial tissue as well as degeneration of seminal tubule epithelium,
      disruption ofspermatogenesis and subsequent decrease of sperm cell number in the
      tubule lumen. These changes were noticed mainly 10 days after LPS treatment. Lack
      of either TCRalphabeta+ CD8+ or TCRgammadelta+ lymphocytes diminishes the
      response of testicular macrophages to LPS whereas the absence of CD1d-dependent
      NKT cells does not affect macrophage reactivity.

PMID- 24745152
TI  - Differences in the expression of human papillomavirus type 16 (HPV-16) E6
      oncogene mRNA in SiHa cell line inoculated with CMV, HSV or ureaplasmas.
AB  - One of the factors associated with an increased risk of HPV-related malignant
      transformation may be bacterial and/or viral infections. The aim of our study was
      to examine whether the presence of infectious agents commonly detected in the
      genitourinary tract such as herpesviruses (HSV, CMV), and ureaplasmas (Ureaplasma
      urealyticum, Ureaplasma parvum) may lead to alterations in the expression of the
      HPV-16 E6 oncogene. Quantitative RT-PCR analysis was used to assess the level of
      HPV-16 E6 mRNA expression in SiHa cells. The presence of HSV-1 or HSV-2 in SiHa
      cells caused a 1.5-fold increase in HPV-16 E6 mRNA expression as compared with
      non-inoculated SiHa cells. Ureaplasma urealyticum presence but not Ureaplasma
      parvum stimulated the expression of HPV-16 E6 resulting in a nearly five-fold
      (4.8) up-regulated E6 mRNA level in SiHa cells. Our study is the first to suggest
      that infection of Ureaplasma urealyticum in an urogenital tract could increase
      the risk of cervical cancer by overexpression of the HPV E6 oncogene.

PMID- 24745153
TI  - [Intrauterine therapy for nonimmune hydrops fetalis (NIHF)--analysis of 38
      cases].
AB  - OBJECTIVE: The aim of the study was to perform an audit the results of fetal
      therapy in cases of nonimmune hydrops fetalis (NIHF), isolated hydrothorax and
      isolated ascites. METHODS: A total of 38 fetuses (17-35 weeks of pregnancy) were
      included in the study whereas 6 patients were excluded due to abnormal karyotype.
      NIHF was diagnosed in 24 cases, hydrothorax in 4 cases, and ascites in 4 cases.
      Shunts were implanted in 26 (81%) cases and 7 (19%) participants underwent
      therapeutic cordocentesis. RESULTS: After therapy anterior-posterior diameter of
      the right and the left lung increased to 9.6 mm (27%) and 12.4 mm (35%),
      respectively. Early complications were observed in 5 (16%) cases. PROM 2 (40%),
      fetal death 1 (20%), infection 1 (20%), and preterm delivery 1 (20%). Out of the
      27 patients, 65% had a caesarian section without early complications and 35% had
      a vaginal delivery with 58% at term and 42% pre-term. CONCLUSIONS: Preceding
      results show that intrauterine therapy significantly improves prognosis of
      fetuses with NIHF.

PMID- 24745154
TI  - [Correlation between serum levels of bile acids in pregnant women with
      intrahepatic cholestasis of pregnancy and condition of their newborns].
AB  - OBJECTIVES: The aim of the study was to determine a relation between the level of
      total serum bile acids in pregnant women and the condition of their newborns on
      the basis of select parameters of acid-base balance in the cord blood. MATERIAL
      AND METHODS: The study group consisted of 64 pregnant women with Intrahepatic
      Cholestasis of Pregnancy and 78 healthy pregnant women constituted the control
      group. Colorimetric enzymatic measurements of serum total bile acids were
      performed in both groups. RESULTS: In the mild cholestasis group, mean
      concentration of bile acids amounted to 20.6 +/- 1.0 micromol/l and was
      statistically significantly lower as compared to women with severe cholestasis
      (58.9 +/- 9.5 micromol/l). In the control group, mean concentration of bile acids
      was 4.1 +/- 0.3 micromol/l and was statistically significantly lower as compared
      to groups with cholestasis. Caesarean section was performed in 60.9% of women
      with cholestasis as compared to 19.2% of controls. Also, neonatal condition in
      the first minute of life was worse in the group with cholestasis as compared to
      the infants in the control group. The body weight of newborns of mothers with
      cholestasis was statistically significantly lower than in infants born to
      controls. Lowered neonatal pH (below 7.20) was noted in 2.6% of the newborns from
      the control group and was statistically significantly less frequent as compared
      to infants from the group with cholestasis. CONCLUSIONS: Periodic measurements of
      total bile acid concentrations in serum of pregnant women with cholestasis is of
      high value in establishing the diagnosis and determining severity of the disease
      in the mother as well as potential hazard for the fetus. Simultaneous monitoring
      of the changes total bile acids concentrations in the blood serum and the well
      being allows to reduce the rates of neonatal distresses after birth and cesarean
      sections.

PMID- 24745155
TI  - High live birth rate after conservative treatment of ectopic pregnancy with
      methotrexate.
AB  - OBJECTIVES: The aim of the study was to assess fertility in patients diagnosed
      with ectopic pregnancy and treated with methotrexate, as well as safety and
      efficacy of conservative treatment. Also, risk factors of recurrent ectopic
      pregnancies were determined. MATERIAL AND METHODS: The study included 86 female
      patients with ectopic pregnancy hospitalized and treated in the clinic of
      Gynecological Endocrinology, UJCM, Cracow, between 2007 and 2011. A total of 73
      patients received a single dose of MTX in the amount of 50 mg/m2 of body surface
      area. Serum b-hCG concentration was measured on days 4 and 7. The treatment was
      considered successful when b-hCG concentrations dropped to less than 0.2 mIU/ml
      without surgery. RESULTS: Among 34 patients on follow-up, 8 (23.5%) did not
      attempt to conceive again, whereas 26 patients declared their wish to conceive
      again. The attempt proved to be successful in case of 16 women (61.53%), and they
      gave birth to healthy children. Average time to pregnancy was 14.9 months (SD +/-
      10.9). The first pregnancy occurred after 6 months and the last after 35 months.
      No congenital birth defects were found in the newborns. CONCLUSIONS: Systemic,
      conservative treatment with methotrexate is an effective and safe way of managing
      ectopic pregnancy even in cases with higher b-hCG concentrations. Most patients
      can be successfully treated without surgery thus they may even be treated in
      outpatient settings. High fertility can be maintained and is independent of the
      skills of the operators and access to laparoscopic techniques. Conservative
      treatment does not increase the risk of recurrent ectopic pregnancy but should be
      offered in wards that provide 24-hour surgical care.

PMID- 24745156
TI  - [Incidence of proapoptotic proteins p53 and p21 in epithelial ovarian tumors].
AB  - OBJECTIVE: The aim of the study was to evaluate the expression of proapoptotic
      proteins p53 and p21 in cystadenomas, borderline tumors and ovarian cancers. The
      correlation between proapoptotic proteins and selected parameters of ovarian
      tumors was also assessed. MATERIAL AND METHODS: The study group consisted of 66
      patients operated on because of epithelial ovarian tumor The study group was
      further divided into three subgroups: cystadenomas, borderline tumors and ovarian
      cancers. RESULTS: The average value of p53 was the highest in the ovarian cancer
      group (50.12 +/- 39.52), whereas average value for p21 was the highest in
      patients with borderline tumors (24.41 +/- 24.43). There was a negative
      correlation between tumor stage and parameters of p21(+++), p21(++), p271 (+) but
      no correlation was found between the expression of p53, p21 and histological type
      of ovarian cancer. CONCLUSION: The assessment of p53 and p21 can be expensive,
      but it proves to be a useful tool in difficult cases. Positive reaction to p53
      can be noted in both, benign and malignant ovarian tumors, but in case of cancer
      its intensity is notably stronger.

PMID- 24745157
TI  - Early postoperative complications of transvaginal access in minimally invasive
      sigmoid colon procedures.
AB  - OBJECTIVES: The aim of the study was to evaluate early (the first 30 days)
      postoperative complications after transvaginal resection of the sigmoid colon.
      MATERIAL AND METHODS: A total of 23 laparoscopy-assisted transvaginal resections
      of the sigmoid colon and 1 NOTES transvaginal sigmoid resection were performed in
      the course of 3 years. Postoperative complications were recorded in a prospective
      manner. RESULTS: In the group of 24 patients operated on using the transvaginal
      approach, 6 (25%) complications were recorded, including 3 urinary tract
      infections, 2 vaginal bleedings, and 1 abdominal trocar site hernia. CONCLUSION:
      Early postoperative complication rate after transvaginal resection of the sigmoid
      colon is relatively low and the clinical complications are not severe.

PMID- 24745158
TI  - The correlation between immunohistochemical expression of MMP-2 and the prognosis
      of epithelial ovarian cancer.
AB  - OBJECTIVES: The Objectives: The goal of the study was to evaluate the correlation
      of matrix metalloproteinase-2 (MMP-2) expression with tumor spread, metastasis,
      survival and recurrence in early and advanced-stage Epithelial Ovarian Cancer
      (EOC). MATERIAL AND METHODS: Medical records of patients, hospitalized at the
      Department of Obstetrics and Gynecology Izmir Ataturk Training and Research
      Hospital between 2003 and 2008, were reviewed. Patient age, tumor size,
      localization, histologic type and tumor grade, stage, metastasis status, patient
      outcomes and follow-up data were obtained from the records of the obstetrics and
      gynecology clinic, as well as during face-to-face or telephone interviews.
      RESULTS: The percentage of MMP-2 staining (expression) in the epithelial cells
      was not significantly associated with tumor stage and grade, histologic type,
      tumor diameter recurrence and overall survival (p > 0.05). A significant
      correlation was found between the percentage of MMP-2 staining (expression) and
      metastasis status (p < 0.05). The staining intensity of MMP-2 was not
      significantly associated with tumor stage and grade, diameter recurrence,
      metastasis and overall survival (p > 0.05), but was with histologic type (p <
      0.05). Total scores were not significantly associated with tumor stage and grade,
      histologic type, tumor diameter recurrence, metastasis and overall survival (p >
      0.05). Stromal staining (expression) of MMP-2 was not significantly correlated
      with tumor stage and grade, histologic type, tumor diameter and outcomes (p >
      0.05), but was with recurrence and presence of metastasis (p < 0.05). No
      significant association was found between the overall survival and percentage of
      MMP-2 staining (p > 0.05), total score (p > 0.05) and staining intensity (p >
      0.05). The association of disease-free survival with the percentage of MMP-2
      staining (p > 0.05), total score (p > 0.05), staining intensity (p > 0.05) and
      stromal staining (p > 0.05) was not statistically significant. The survival of
      patients with positive stromal staining was significantly shorter compared to
      cases with negative stromal staining (p < 0.05). CONCLUSIONS: Large-scale,
      comprehensive research is needed to verify whether MMP 2 may be used as a routine
      prognostic factor for EOC.

PMID- 24745159
TI  - [The effect of prolactin and apolipoprotein E gene polymorphism on cognitive
      functions of menopausal women].
AB  - OBJECTIVE: The objective of the study was to analyze a possible association
      between cognitive functions and level of prolactin in menopausal women with
      different polymorphisms of apolipoprotein E gene (APOE). The examined population
      included women from the south-eastern part of Poland; aged 50-65 years; at least
      2 years after their last menstruation; in good health; with at least primary
      education, FSH > 30 mIU/ml. The MoCA test (Montreal Cognitive Assessment Test)
      allowed us to exclude women with signs of dementia. The cognitive functions
      assessment was conducted with the CNS-VitalSigns diagnostic equipment (Polish
      version). The prolactin designations were conducted by SYNEVO--an accredited
      laboratory. The examination of APOE polymorphism was performed using the
      multiplex-PCR method. The results were statistically analyzed. RESULTS AND
      CONCLUSION: Higher level of prolactin turned out to be associated with better
      test results in the following areas: NCI, memory verbal memory psychomotor speed
      and concentration. Women with higher level of prolactin had better results in
      NCI, psychomotor speed and verbal memory tests. The test results of other
      cognitive function were not unequivocally related to higher levels of prolactin.
      Thus, it was not possible to conclude that the presence of APOE polymorphism is
      related to the effect of prolactin on cognitive functions of the examined
      menopausal women.

PMID- 24745160
TI  - [Ultrasound evaluation of fetal adrenal gland volume. The role of fetal adrenal
      glands in the pathogenesis of preterm labor].
AB  - Preterm labor remains to be one of the most important challenges of contemporary
      perinatology and constitutes the main reason of perinatal mortality and
      prematurity of neonates. Studies on preterm labor have confirmed the mutual
      interactions of several different hormonal systems while the activation of
      hypothalamic- pituitary- adrenal axis seems to have the greatest influence. It
      has been also suggested that size and mass of fetal adrenal glands may be
      associated with the risk of preterm labor. Several authors have shown that the
      evaluation of fetal adrenal gland volume may be a useful marker of fetal growth
      during pregnancy. Technological advancements enabled the development of three
      dimensional ultrasound evaluation (3D) of the fetal adrenal glands, facilitating
      a more precise evaluation of their volume. Also, it seems to have higher
      sensitivity and specificity than two-dimensional ultrasonography (2D). Studies
      have confirmed a direct relationship between fetal adrenal gland size and the
      onset of preterm labor within at least 1 week since the ultrasound exam. They
      have also suggested that in a physiological pregnancy the relation between fetal
      zone and the whole organ remains constant throughout the pregnancy. Disruption of
      these proportions and fetal zone enlargement are considered to be a marker of
      labor cascade and preterm labor with significantly higher sensitivity and
      specificity than ultrasound evaluation of the cervical length and assessment of
      the fetal fibronectin concentration.

PMID- 24745161
TI  - [Diagnosing polycystic ovary syndrome in adolescent girls].
AB  - Polycystic ovary syndrome (PCOS) is one of the most common endocrinopathies and
      it manifests itself in about 4-12% women of reproductive age. The Rotterdam, AES
      and NIH criteria can be used to diagnose PCOS in adults but there are no specific
      criteria to diagnose PCOS in adolescent girls. Most authors agree that applying
      criteria for adult to teenagers leads to overdiagnosis because of similarity in
      physiological changes during puberty and common PCOS symptoms. Tightening of the
      current criteria and including new, not widely accepted yet, was proposed.
      Currently it seems justifiable to diagnose PCOS in adolescent girls using the
      Rotterdam criteria, on condition that all three symptoms are present,
      hyperandrogenism is established in laboratory tests and pelvic ultrasound reveals
      an increased ovarian volume (> 10 ml). Nevertheless, the necessity of more
      research and establishing specific criteria for adolescent girls is emphasized.

PMID- 24745162
TI  - Endometrial receptivity-- can it be diagnosed and controlled? And why does it
      matter?
AB  - Infertility remains a challenge to modern medicine. Despite extensive diagnostic
      and therapeutic procedures, the achievement of pregnancy remains an elusive goal
      in some patients. The endometrium is one of the key factors in embryo
      implantation. Older methods of describing endometrial receptivity like histology
      or ultrasound, did not bring noticeable improvement in pregnancy rates. New
      technologies, including genomics, proteomics, lipidomics, and secretomics promise
      to improve the detection of the implantation window in the endometrium and result
      in better counseling of patients with infertility.

PMID- 24745163
TI  - Live birth of monochorionic triamniotic triplets after in vitro fertilization and
      blastocyst transfer: case report and review of the literature.
AB  - Monozygotic triplet pregnancies are very rare, even after in vitro fertilization
      (IVF). We present a case of a live birth of triplets from a monochorionic
      triamniotic pregnancy after blastocyst transfer. A 29-year-old woman underwent
      intracytoplasmic sperm injection (IVF-ICSI). Her medical history included a 4
      year infertility treatment with ovarian stimulation, three cycles of intrauterine
      insemination, hysteroscopy and an unsuccessful attempt at IVF. During the second
      IVF attempt, the patient underwent ovulation simulation according to the long
      GnRH agonist protocol. Eleven metaphase II (MII) oocytes were injected with
      spermatozoa, resulting in four expanded blastocysts. In the end, two blastocysts
      (4AA) were transferred into the uterine cavity. Ultrasound examination performed
      at 7 weeks of gestation showed an ongoing triamniotic triplet pregnancy. Regular
      uterine contractions began at 33 weeks of gestation and a cesarean section was
      performed, resulting in a birth of three healthy girls, weighing 2060g (Apgar 7),
      1860g (Apgar 6), 2000g (Apgar 6). After 13 days of hospitalization the infants
      and the mother were discharged home. CONCLUSION: The causes of monozygotic
      multiple gestations in spontaneous and ART pregnancies are poorly understood.
      They seem to occur more often after IVF. Any definitive relationship between
      particular stages of the IVF procedure and monozygotic multiple pregnancies
      remains controversial.

PMID- 24745164
TI  - [Statement of the Polish Gynecological Society on the application of myo-inozytol
      in patients with PCOS (polycystic ovary syndrome)].

PMID- 24745165
TI  - [Endothelium in physiology and pathogenesis of diseases].
AB  - Vascular endothelium is the layer of cells that line blood vessels and serve as
      the primary barrier between the blood and the tissues. These cells play many
      important functions such as regulation of the vascular tone, blood flow and
      pressure control, maintaining the balance between thrombosis and fibrinolysis,
      participation in immune system reactions and new blood vessels formation.
      Disturbance in any of these functions may contribute to the development of
      different diseases such as for e.g. hypertension, atherosclerosis and deep vein
      thrombosis, as well as cancer.

PMID- 24745166
TI  - Hemogenic endothelium--ontogenesis and role in blood production.
AB  - Endothelial and hematopoietic lineages have long been thought to develop from a
      common ancestor, the hemangioblast. Alternatively, clusters of hematopoietic
      cells in the dorsal aorta were observed to form in a close association with
      endothelial wall of the aorta, leading to the hypothesis that a special subset of
      endothelial cells, called the hemogenic endothelium, generates hematopoietic
      cells. Recent advances in time-lapse imaging, conditional labeling of cells in
      vivo and embryonic stem cell differentiation provided new evidence for the
      existence of both, the hemangioblast and hemogenic endothelium. Importantly,
      these seemingly contradictory theories can be merged into one model of
      hematopoietic differentiation from mesoderm.

PMID- 24745167
TI  - Heterogeneity of endothelial cells--role in vessel specialization and cooperation
      in vasculogenic mimicry.
AB  - Among endothelial cells (ECs), subpopulations are mainly distinguished in terms
      of maturation, tissue specialization and functions. Heterogeneity is an important
      characteristic of endothelial cells responsible for organ-specific cell and
      molecule delivery. Endothelial cell heterogeneity is a key to embryonic
      development as well as cell recruitment in adult organism during the immune
      response; it determines also the pathologic spreading of diseases, such as cancer
      invasion and infectious disease progression among species. Heterogeneity is also
      a feature of intra-organ specialization of endothelial cells. ECs are highly
      reactive to the microenvironment and their condition reflects healthy vs.
      diseased states. They respond to tissue hypoxia which brings a new parameter to
      endothelial heterogeneity. Hypoxia changes the phenotype and biology of ECs by
      turning on angiogenesis to restore physioxia. Highly responsive to hypoxia are
      the endothelial precursor cells (EPCs) and the selected cancer stem cell (CSC)
      populations, the most aggressive dedifferentiated tumor cells. They cooperate
      with one another and contribute to the vascular mimicry process of angiogenesis.
      This has a most effective impact on tumor cells escape and spreading.

PMID- 24745168
TI  - [Lymphatic endothelium].
AB  - Compared to the knowledge about the structure and function of endothelial cells
      of blood vessels, which was heavily developed over the past few decades, advance
      in the knowledge of lymphatic endothelial cells (LECs) for many years has been
      impossible, because of the lack of specific methods that allow histological
      visualization of lymphatic vessels in the tissues. The last years have brought
      significant progress in this field. Identification of specific markers of LECs
      and the development of new experimental animal models have allowed to recognize a
      number of antigens and growth factors of LECs and to isolate pure LECs
      populations. Studies indicate heterogeneity and plasticity of LECs and their
      active participation in the extracellular homeostasis, lipid transport, immune
      response and in the pathophysiology of acute and chronic inflammatory diseases,
      graft rejection and cancer. The article presents the current knowledge on the
      importance and regulation of LECs, both in health and disease.

PMID- 24745169
TI  - [Aerobic metabolism and reactive oxygen species in endothelial cells].
AB  - Endothelium is a single layer of cells lining each blood vessel that accomplishes
      a vast variety of specialized functions, which variations are implicated in the
      development of many cardiovascular diseases. Mitochondria are found in most human
      cells, however the ATP synthesis in endothelium occurs in a major part via a
      glycolytic pathway. The relatively slight dependence of endothelial cells on
      mitochondrial oxidative phosphorylation could suggest that mitochondria play no
      significant role in endothelium. Several recent observations clearly indicate
      that endothelial mitochondria not only can contribute to ATP generation but also
      are involved in maintaining the fine regulatory balance among mitochondrial
      calcium concentration, reactive oxygen species production and NO production. The
      endothelial mitochondria may function as a sensor of alternations in the local
      environment, contributing to survival of endothelial cells under oxidative
      stress. Mitochondrial reactive oxygen species are significant signaling molecules
      in endothelium. Endothelial mitochondria may play a central role in many
      cardiovascular disease.

PMID- 24745170
TI  - [Microparticles in endothelial function].
AB  - The paper is an introduction to the issue of endothelial microparticles, their
      biology and function. The historical view of microparticle research and actual
      knowledge about microaprticle formation, structure and molecular composition are
      presented. The new directions of endothelial microparticle research are discussed
      with the emphasis of their coagulation aspects.

PMID- 24745171
TI  - [Role of microRNA in endothelial cells--regulation of differentiation and
      angiogenesis].
AB  - Endothelium has an immense impact on the tissue regeneration, regulation of
      atherosclerosis and tumour growth. Therefore, modification of endothelial cell
      differentiation and function seems a promising target for many therapies.
      MicroRNAs are small RNA molecules, which recognize and inhibit specific mRNAs. In
      that way, they can regulate and orchestrate whole signalling pathways. It has
      been shown that microRNAs can fine-tune endothelial cell functions since they
      have either pro- and antiangiogenic activity, regulate expression of e.g.
      adhesion molecules or nitric oxide synthase. Furthermore, microRNAs modulate
      differentiation of embryonic stem cells to endothelial cells and their further
      specialization towards specific vascular bed. This review focuses mainly on the
      influence of microRNA on the angiogenesis and endothelial cell differentiation.

PMID- 24745172
TI  - Vascular endothelium--role in chronic inflammatory disease.
AB  - The vascular endothelial lining of blood vessels plays a key 'target-effector'
      role in vivo, integrating the body's response to inflammatory cytokines,
      chemokines and growth factors (derived from both endothelial cells themselves and
      from other cells such as leukocytes and fibroblasts), to allow leukocyte
      activation, adhesion and extravasation from the flowing blood into underlying
      tissue. Endothelial proliferation, through the process of angiogenesis, results
      in an increased cell surface area for these events to occur, and further
      functions to deliver oxygen and nutrients, and to remove waste products. In
      addition to playing an important role in physiology, the endothelium is thus an
      active participant in inflammatory pathologies. One of the best understood
      diseases in which inflammation and angiogenesis play a part is rheumatoid
      arthritis (RA). Blockade of the inflammatory cascade in RA has significant
      consequences for the vasculature, highlighting the links between reducing
      endothelial activation and therapeutic benefit in chronic inflammatory disorders.

PMID- 24745173
TI  - [Oxidative stress and vascular function].
AB  - The maintenance of blood vessel homeostasis is closely associated with Reactive
      Oxygen and Nitrogen Species (ROS and RNS) production in the blood vessel wall.
      The main molecules taking part in this process are nitric oxide (NO), superoxide
      anion (O2*-), hydrogen peroxide (H2O2) and their derivatives. The production of
      these factors occurs in health and disease, however the increased ROS release is
      often referred to as oxidative stress. While initially oxidative stress was
      considered systemically, recent data indicate that it occurs locally in
      subcellular spaces and may be a result of dysfunction of individual enzyme
      systems. Oxidative stress induces inflammation, proliferation and migration of
      vascular smooth muscle cells, may regulate apoptosis and the function of the
      cells of vascular wall, finally leading to dysfunction of endothelium, media and
      adventitia, leading to cardiovascular diseases such as atherosclerosis,
      hypertension or heart failure. It is believed that a family of NADPH oxidases is
      the main source of ROS in the vessel wall, but also in other organs and tissues.
      It consists of seven known and quite precisely characterized homologues (NOX1,
      NOX2, NOX3, NOX4, NOX5, DUOX1 and DUOX2) which often have very distinct activity
      and cellular localization and function. Besides harmful actions, we are beginning
      to understand the protective effects of ROS and RNS. They have many functions
      regulating redox-sensitive gene expression and influencing a proper function of
      cells and vessels. NOX4 has been particularly well characterized in this respect.
      Thus, the maintenance of the right homeostasis depends not only on ROS removing
      capabilities, but especially on preserving the adequate level of ROS production.

PMID- 24745174
TI  - [The detection of nitric oxide and NO-derivatives in the endothelial cells and
      tissues].
AB  - The correctly working endothelium produces suitable quantities of nitric oxide
      (NO) and other mediators, necessary for maintenance of homeostasis of
      cardiovascular system. Because of correlation between the availability of NO and
      the physiological state of the whole organism, monitoring the concentration of
      nitric oxide is essential for the better understanding of pathogenesis of many
      diseases. For this reason, there are intensive studies performed to develop new
      methods allowing the control of NO concentration in biological specimens. Thus,
      we should pay a special attention on the methods which make possible the
      measurement of the concentration of nitric oxide and reactive oxygen species
      (ROS). They can be based on analysis of adducts formed by ROS with different
      stable complexes, on measurement of the direct products of oxygenation, or on the
      reduction of radicals. Electron paramagnetic resonance (EPR) deserves special
      attention, as it allows for the direct measurement of free radical signals or for
      analysis of stable adducts of radicals with the spin traps. Other methods should
      be used, however, to confirm and extend the results of EPR examination.

PMID- 24745175
TI  - [90th anniversary of Occupational Medicine Department in I.I. Metchnikov North
      Western State Medical University--results, achievements, prospects].
AB  - The authors briefly report history, development, achievements and prospects of
      Occupational Medicine Department in I.I. Metchnikov North-Western State Medical
      University.

PMID- 24745176
TI  - [Basic concepts of occupational longevity of workers in Russia].
AB  - The article represents comparative analysis of ageing process in demographic
      transition context. Demographic problems in Russia are stated. The authors give
      special attention to demographic and occupational risks of decrease in able
      bodied population, increased burden on able-bodied population. The authors prove
      necessity of further research on innovation technologies in gerontology for means
      and methods to prevent early decrease in occupational capacity, to delay ageing
      process in workers, to lower mortality and increase occupational longevity.

PMID- 24745177
TI  - [Methodology of occupational fitness examination: problems and ways to
      solutions].
AB  - The article covers improvement of occupational fitness examination methodology in
      workers exposed to occupational hazards, based on longstanding experience of
      practical work in industrial medicine. The authors examined main causes of
      controversies and conflict situations in occupational fitness examination,
      possible ways to solve the problems in accordance with contemporary evidence
      based medicine principles.

PMID- 24745178
TI  - [Problems of diagnosis and prevention of occupational malignancies].
AB  - The authors presented statistics on quantity of registered occupational
      malignancies in Russian Federation and some foreign countries, analyzed causes of
      difficult diagnosis of occupational malignancies, suggested ways to improve the
      situation.

PMID- 24745179
TI  - [Analysis of occupational morbidity and ways of further improving occupational
      therapy in Leningrad region].
AB  - Retrospective clinical and epidemiologic analysis covered occupational diseases
      in Leningrad region. Findings are that over recent years a tendency to lower
      number of primarily diagnosed occupational diseases continues. The authors
      justify necessity to work out the programs on prevention of occupational diseases
      in the region.

PMID- 24745180
TI  - [Problem of electromagnetic safety in contemporary scientific progress].
AB  - The article covers problems of human electromagnetic safety in intensive
      development of new generation radio-frequency equipment with complicated physical
      and technical properties. The authors suggest national program on electromagnetic
      safety.

PMID- 24745181
TI  - [Medical service and health state of vehicle drivers of city water supply and
      sewerage enterprise].
AB  - The article covers data on medical service system and health state of vehicle
      drivers on major water supply and sewerage enterprise.

PMID- 24745182
TI  - [Hygienic evaluation of contemporary light sources].
AB  - The article covers problems of illumination hygiene and electromagnetic safety of
      workers using contemporary light sources. The authors present results of
      experimental studies of electromagnetic environment in energy-efficient lamps.

PMID- 24745183
TI  - [Experience of international cooperation among Baltic countries in occupational
      health and security].
AB  - The article covers longstanding experience of international cooperation in
      occupational health and security with Baltic countries. The authors describe
      history of information network creation, its structure, objectives, importance
      for occupational health services and safety in the region.

PMID- 24745184
TI  - [N.A. Vigdortchik--outstanding national scientist, teacher and public figure, as
      founder of scientific occupational medicine school in Leningrad (to the 140th
      birthday)].
AB  - The authors analyze activities of N.A. Vigdortchik as a founder of scientific,
      teaching and practical directions in doctors' work on occupational problems and
      industrial hygiene in Leningrad.

PMID- 24745185
TI  - [A.V. Zinserling (Tsinzerling) school of infectious pathology: advances and
      prospects].
AB  - The paper analyzes the importance of infectious pathology today and discusses the
      main achievements of A.V. Zinserling (Tsinzerling) and his collaborators when
      having studied the pathologic anatomy of infectious diseases, primarily
      respiratory, intestinal, intrauterine ones. An indication is given to the
      significance of clinic and morphological comparisons, a problem of mixed
      infections. There is evidence that A.V. Zinserling's studies have opened the new
      area of science tissue microbiology in which some progress has been also achieved
      in recent years.

PMID- 24745186
TI  - [The molecular biological characteristics of the pathogen of tuberculosis and the
      pathoanatomic aspects of its fatal outcomes in Irkutsk in 2008-2011].
AB  - The paper gives the results of examining 163 autopsy cases of tuberculosis in
      Irkutsk. The forms of the disease are characterized, by identifying generalized
      large focal necrotic focal tuberculosis. MIRU-VNTR genotyping defined M.
      tuberculosis genotypes and established the leading role of the Beijing genotype
      (65%) in the development of the most severe generalized alterative and exudative
      changes. 48% of all generalized large focal tuberculosis cases were shown to be
      HIV-infected. A DS-SIGN gene polymorphism at the -336 A/G position was studied;
      the most unfavorable combination of AG or GG polymorphism (in 84% of cases) was
      shown in a patient with the M. tuberculosis Beijing genotype. Not only the
      patient's immune status, but also the genotypes of mycobacteria and the host
      affect the most unfavorable course of tuberculosis with the development of
      generalized alterative and exudative lesions.

PMID- 24745187
TI  - [Fas, FasL, and bcl-2 expression on hepatic intralobar lymphocytes in different
      variants of the natural course of chronic HBV and HCV infection and in its
      outcomes].
AB  - The investigation revealed the specific features of cell-mediated hepatocyte
      damage in different variants of the natural course of chronic HBV and HCV
      infection and in its outcomes (chronic hepatitis, liver cirrhosis, and
      hepatocellular carcinoma), by determining the expression of proapoptotic (Fas,
      FasL) and antiapoptotic (bcl-2) factors on the surface of intralobular
      lymphocytes. Comparative analysis of the magnitude and pattern of cell
      infiltration in the liver parenchyma, the functional activity of intralobular
      lymphocytes showed significant differences in the above indicators in relation to
      the etiology and stage of the pathological process, suggesting that there were
      different pathogenetic mechanisms of their natural course. There was a varying
      potential readiness of intralobular lymphocytes for apoptosis, giving rise to
      different clinical manifestations in the similar morphological picture.

PMID- 24745188
TI  - [Evaluation of the placental morphofunctional state in perinatal HIV
      transmission].
AB  - The paper presents the results of investigating the mechanisms of placental
      insufficiency and transplacental infection of infants born to HIV-infected
      mothers who have received specific antiretroviral therapy mothers and who have
      not.

PMID- 24745189
TI  - [The morphological examination in the differential diagnosis of tuberculosis and
      sarcoidosis].
AB  - The paper considers the results of histological and bacterioscopic examinations
      of biopsy specimens from the lung and mediastinal lymph nodes of 120 patients
      with an unclear diagnosis of tuberculosis and sarcoidosis and with problem of
      their differential diagnosis. One hundred and five of these patients were
      microscopically diagnosed as having either tuberculosis or sarcoidosis.
      Additional examination of differently stained sections and that using
      immunohistochemical M. tuberculosis detection were conducted in 15 cases, which
      could diagnose tuberculosis and sarcoidosis in 7 and 8 patients, respectively.
      Bacterioscopic examination, in terms of extreme variability the phenotypic
      properties of mycobacteria, is of decisive importance in the differential
      diagnosis of tuberculosis and sarcoidosis.

PMID- 24745190
TI  - [Papillomavirus in the genesis of oral leukoplakia].
AB  - Immunohistochemical examination of the proliferative activity of cells was made
      investigating the expression of Ki-67 protein and the location of proteins
      associated with epithelial cell papillomavirus infection involving P16(INK4a) and
      HPV16 proteins in different cell areas of the intact mucosa, in leukoplakia with
      the signs of hyperplasia and dysplasia, and in squamous cell carcinoma. There was
      a positive correlation between the proliferative activity of cells in the
      parabasal cell areas and the expression of P16(INK4a) protein in oral leukoplakia
      with the signs of hyperplasia (r(s)=0.397; p=0.018). In oral leukoplakia with
      dysplastic changes, there was a positive correlation between the proliferation of
      cells in the parabasal and prickle cell layers and the location of HPV type 16
      antigens (r(s)=0.515; p=0.041 and r(s)=0.651; p=0.006). Detection of
      papillomavirus infection in leukoplakia can solve not only the problems with its
      genesis, but this is also a morphological basis for the effective prevention and
      treatment of this common oral mucosal disease.

PMID- 24745191
TI  - [Structural changes in the gastric and duodenal mucosal capillaries in asthma].
AB  - Morphological examination of microcirculatory bed vessels in the gastric and
      duodenal mucous membranes was performed in asthmatic patients. The gastroduodenal
      area showed signs of capillary dysfunction and a vascular component of mucosal
      remodeling, like bronchial wall remodeling in asthma.

PMID- 24745192
TI  - [Clinical and morphological characteristics of renal hypoplasia in children].
AB  - The course of the disease was studied in children with renal hypoplasia on the
      basis of the results of clinical observations and analysis of autopsy protocols.
      The data of clinical observations of 236 children aged 0 to 15 years were
      analyzed. Complications and cause of death were assessed; concomitant
      malformations were analyzed with consideration for pathoanatomic findings. The
      results indicated that diverse hypoplastic malformations were in other organs and
      systems. The spectrum and location of congenital malformations were various.
      Bilateral involvement was most common in died children. There is a high rate of
      congenital malformations in the small pelvis and chest of these patients. The
      degree of renal dysfunction much varies in children with renal hypoplasia.

PMID- 24745193
TI  - [Reparative osteogenesis after incorporation of roncoleukin into therapy for
      experimental tuberculous gonitis].
AB  - The authors evaluated reparative osteogenesis after incorporation of roncoleukin
      into combination therapy for experimental drug-resistant tuberculous osteitis.
      Roncoleukin (12.5 pg/kg, 5 injections, once every 3 days) was used during
      antituberculosis therapy before and after combined plasty (autobone + OsteoSet-T)
      in repairing surgical defects. When used in the postoperative period of combined
      osteoplasty, roncoleukin was shown to contribute to a reduction in the spread of
      specific inflammatory foci in bone tissue, cessation of an alternative necrotic
      component, an increase in the rate of osteogenesis with newly formed bone
      trabeculae, and activation of hematopoietic processes in the bone marrow. In
      parallel with intensified bone reparative processes, there was immunomodifier
      induced stimulation of the absorption and digestion of peritoneal macrophages
      suppressed in experimental tuberculous osteitis.

PMID- 24745194
TI  - [Algorithm for examination of bone marrow trephine biopsy specimens in
      myelodysplastic syndromes].
AB  - Based on the analysis of more than 1000 bone marrow trephine biopsy specimens
      from patients with myelodysplastic syndromes before starting any specific
      therapy, the authors propose histological criteria for their evaluation (an
      examination algorithm), an optimal panel of immunohistochemical examination, and
      histological criteria for predicting the course of the disease.

PMID- 24745195
TI  - [Chlamydial infection of the central nervous system. Laboratory diagnosis and
      clinic and morphological features].
AB  - The paper presents data on the diagnosis, clinical and pathomorphological changes
      in the central nervous system (CNS) in neurochlamydiasis according to clinical,
      autoptic, and experimental evidence. It discusses the possible implication of Ch.
      trachomatis, Ch. pneumoniae, and Ch. psittaci in the development and course of
      different diseases with CNS involvement: atherosclerosis, vasculitis, multiple
      sclerosis, Alzheimer's disease, schizophrenia, autism, vegetative state, sequels
      of perinatal lesions in childhood and adolescence, HIV infection, etc.
      Considerable attention is paid to the specific features of diagnosis of Chlamydia
      induced CNS lesions. Purposeful pathomorphological investigations are shown to be
      needed.

PMID- 24745196
TI  - [Aleksandr Vsevolodovich Zinserling (Tsinzerling) is a respectable person, an
      investigator, a teacher (on the occasion of his 90th birthday)].

PMID- 24745197
TI  - Effectiveness of shared leadership in Wikipedia.
AB  - OBJECTIVE: The objective of the paper is to understand leadership in an online
      community, specifically, Wikipedia. BACKGROUND: Wikipedia successfully aggregates
      millions of volunteers' efforts to create the largest encyclopedia in human
      history. Without formal employment contracts and monetary incentives, one
      significant question for Wikipedia is how it organizes individual members with
      differing goals, experience, and commitment to achieve a collective outcome.
      Rather than focusing on the role of the small set of people occupying a core
      leadership position, we propose a shared leadership model to explain the
      leadership in Wikipedia. Members mutually influence one another by exercising
      leadership behaviors, including rewarding, regulating, directing, and socializing
      one another. METHOD: We conducted a two-phase study to investigate how distinct
      types of leadership behaviors (transactional, aversive, directive, and person
      focused), the legitimacy of the people who deliver the leadership, and the
      experience of the people who receive the leadership influence the effectiveness
      of shared leadership in Wikipedia. RESULTS: Our results highlight the importance
      of shared leadership in Wikipedia and identify trade-offs in the effectiveness of
      different types of leadership behaviors. Aversive and directive leadership
      increased contribution to the focal task, whereas transactional and person
      focused leadership increased general motivation. We also found important
      differences in how newcomers and experienced members responded to leadership
      behaviors from peers. APPLICATION: These findings extend shared leadership
      theories, contribute new insight into the important underlying mechanisms in
      Wikipedia, and have implications for practitioners who wish to design more
      effective and successful online communities.

PMID- 24745198
TI  - Viewing the workload of vigilance through the lenses of the NASA-TLX and the MRQ.
AB  - OBJECTIVE: The aim of this study was to compare the effectiveness of a new index
      of perceived mental workload, the Multiple Resource Questionnaire (MRQ), with the
      standard measure of workload used in the study of vigilance, the NASA Task Load
      Index (NASA-TLX). BACKGROUND: The NASA-TLX has been used extensively to
      demonstrate that vigilance tasks impose a high level of workload on observers.
      However, this instrument does not specify the information-processing resources
      needed for task performance. The MRQ offers a tool to measure the workload
      associated with vigilance assignments in which such resources can be identified.
      METHOD: Two experiments were performed in which factors known to influence task
      demand were varied. Included were the detection of stimulus presence or absence,
      detecting critical signals by means of successive-type (absolute judgment) and
      simultaneous-type (comparative judgment) discriminations, and operating under
      multitask vs. single-task conditions. RESULTS: The MRQ paralleled the NASA-TLX in
      showing that vigilance tasks generally induce high levels of workload and that
      workload scores are greater in detecting stimulus absence than presence and in
      making successive as compared to simultaneous-type discriminations. Additionally,
      the MRQ was more effective than the NASA-TLX in reflecting higher workload in the
      context of multitask than in single-task conditions. The resource profiles
      obtained with MRQ fit well with the nature of the vigilance tasks employed,
      testifying to the scale's content validity. CONCLUSION: The MRQ may be a
      meaningful addition to the NASA-TLX for measuring the workload of vigilance
      assignments. APPLICATION: By uncovering knowledge representation associated with
      different tasks, the MRQ may aid in designing operational vigilance displays.

PMID- 24745199
TI  - Should we be more on the ball? The efficacy of accommodation training on lumbar
      spine posture, muscle activity, and perceived discomfort during stability ball
      sitting.
AB  - OBJECTIVE: The aim of this study was to evaluate the efficacy of a 9-day
      accommodation protocol on reducing perceived discomfort while sitting on a
      stability ball (SB); trunk muscle activity levels and lumbar spinal postures were
      also considered. BACKGROUND: Previous studies have compared SB sitting with
      office chair sitting with few observed differences in muscle activity or posture;
      however, greater discomfort during SB sitting has been reported. These findings
      may indicate an accommodation period is necessary to acclimate to SB sitting.
      METHOD: For this study, 6 males and 6 females completed two separate, 2-hr
      sitting sessions on an SB. Half the participants completed a 9-day accommodation
      period between the visits, whereas the other half did not use an SB during the
      time. On both occasions, self-reported perceived discomfort ratings were
      collected along with erector spinae and abdominal muscle activity and lumbar
      spinal postures. RESULTS: Discomfort ratings were reduced in female participants
      following the accommodation; no effects on muscle activation or lumbar spine
      postures were observed. CONCLUSION: Accommodation training may reduce perceived
      low-back discomfort in females.Trunk muscle activity and lumbar spine postures
      during seated office work on an SB did not differ between groups; however,
      greater sample power was required to conclusively address these variables.
      APPLICATION: Regarding whether to use an SB in place of a standard office chair,
      this study indicates that females electing to use an SB can decrease discomfort
      by following an accommodation protocol; no evidence was found to indicate that SB
      chair use will improve trunk strength or posture, even following an accommodation
      period.

PMID- 24745200
TI  - Shoulder muscle fatigue during repetitive tasks as measured by electromyography
      and near-infrared spectroscopy.
AB  - OBJECTIVE: The objective of this study was to quantify shoulder muscle fatigue
      during repetitive exertions similar to motions found in automobile assembly
      tasks. BACKGROUND: Shoulder musculoskeletal disorders (MSDs) are a common and
      costly problem in automotive manufacturing. METHOD: Ten subjects participated in
      the study. There were three independent variables: shoulder angle, frequency, and
      force. There were two types of dependent measures: percentage change in near
      infrared spectroscopy (NIRS) measures and change in electromyography (EMG) median
      frequency. The anterior deltoid and trapezius muscles were measured for both NIRS
      and EMG. Also, EMG was collected on the middle deltoid and biceps muscles.
      RESULTS: The results showed that oxygenated hemoglobin decreased significantly
      due to the main effects (shoulder angle, frequency, and force). The percentage
      change in oxygenated hemoglobin had a significant interaction attributable to
      force and repetition for the anterior deltoid muscle, indicating that as
      repetition increased, the magnitude of the differences between the forces
      increased. The interaction of repetition and shoulder angle was also significant
      for the percentage change in oxygenated hemoglobin. The median frequency
      decreased significantly for the main effects; however, no interactions were
      statistically significant. CONCLUSIONS: There was significant shoulder muscle
      fatigue as a function of shoulder angle, task frequency, and force level.
      Furthermore, percentage change in oxygenated hemoglobin had two statistically
      significant interactions, enhancing our understanding of these risk factors.
      APPLICATION: Ergonomists should examine interactions of force and repetition as
      well as shoulder angle and repetition when evaluating the risk of shoulder MSDs.

PMID- 24745201
TI  - Interference between accustomed number-space mappings and unacquainted letter
      space mappings in a button press task.
AB  - OBJECTIVE: We aimed to investigate how ordered mappings (e.g., left-to-right and
      right-to-left order representations) would interfere with each other. BACKGROUND:
      Mental representations of numbers and letters are linked with spatial
      representation and can be changed intentionally. METHOD: The experiment consisted
      of three sessions. In the digit-alone session, two digits randomly selected from
      [1], [2], and [3] were shown. If the two digits were the same, participants
      pressed the button corresponding to the digit, and if the digits differed, they
      pressed the remaining button. The response buttons were ordered [1][2][3] from
      the left. In the letter-alone session, three different button configurations were
      prepared: sequential [A][B][C], reversed [C][B][A], or partially reversed
      [B][A][C]. The same-versus-different rules were basically identical to those in
      the digit task. In the mixed session, trials of the digit task and those of the
      letter task were randomly mixed. RESULTS: We found that two ordinal
      representations did not interfere with each other when they shared the same
      direction of order ([1][2][3] vs. [A][B][C]), two ordinal mappings interfered
      with each other when they had different directions of order ([1][2][3] vs. [C][B]
      [A]), and an ordinal mapping ([1][2][3]) was affected by a nonordinal mapping
      ([B][A][C]), but the nonordinal mapping was less affected by the ordinal mapping.
      CONCLUSION: The mapping between ordinal information and space can be modulated by
      top-down processes, and it is prone to interference depending on the nature of
      another coexisting mapping. APPLICATION: Our findings may be used in designing
      response assignments for input devices for multiple functions.

PMID- 24745202
TI  - ReadingMate: the effect of the content stabilizing technique, font size, and
      interline spacing on the letter-counting task performance of treadmill runners.
AB  - OBJECTIVE: The aim of this study was to investigate the effects of font size,
      interline spacing, and a technology called ReadingMate on the letter-counting
      task performance of users running on a treadmill. BACKGROUND: Few researchers
      have investigated how runners read text while running on a treadmill. Our
      previous studies showed that ReadingMate had positive effects on the reading
      while-running experience; however, the effect of other text conditions (i.e.,
      font size and interline spacing) and the interplay between ReadingMate and such
      text conditions on the letter-counting task performance are not clearly
      understood. METHOD: Fifteen participants were recruited for the experiment. There
      were three main factors: display types (normal and ReadingMate), font sizes (8,
      12, 16, and 20 point), and interline spacing (1.0x, 1.5x, 2.0x, and 2.5x). The
      researchers employed a letter-counting task. The performance was measured
      regarding task performance time, success rate of counting the target letter f and
      number of give-ups. RESULTS: Overall, the letter-counting task performance while
      running on a treadmill improved as font size and interline spacing increased, as
      expected. ReadingMate was more effective than normal display particularly when
      text was displayed in a small font size and with dense interline spacing.
      CONCLUSION: When text must be displayed in a small font size and with dense
      interline spacing, ReadingMate can be used to improve the users' task
      performance. APPLICATION: Practical applications of ReadingMate include improving
      the text-reading experience in shaky environments, such as in aviation,
      construction, and transportation.

PMID- 24745203
TI  - Response-effect compatibility defines the natural scrolling direction.
AB  - OBJECTIVE: We evaluated alternative scrolling methods on non-touch screen
      computer operating systems by comparing human performance in different scrolling
      conditions. BACKGROUND: The scrolling directions on current operating systems are
      discrepant. Few researchers have investigated how scrolling method influences
      users performance. The response-effect (R-E) compatibility principle can be used
      as a theoretical guide. METHOD: Experiments 1 and 2 involved two successive tasks
      (scrolling and target content judgment) to simulate how people scroll to acquire
      and use off-screen information. Performance in R-E compatible and incompatible
      conditions was compared. Experiment 3 involved a location judgment task to test
      the influence of target location. Experiments 4 and 5 included a scrolling effect
      following the location judgment task to test the sufficient role of the scrolling
      effect. RESULTS: Overall, responses were facilitated when the response direction
      was compatible with the forthcoming display-content movement direction (an R-E
      compatibility effect), when the scrolling effect was task relevant or task
      irrelevant. A spatial stimulus-response (S-R) compatibility effect attributable
      to target location was also found. When the scrolling effect was present, there
      were both R-E and S-R components; the R-E effect was the larger of the two.
      CONCLUSION: Scrolling in the direction of content movement yielded the best
      performance, and the scrolling effect was the main source of the R-E
      compatibility effect. APPLICATION: These findings suggest that (a) the R-E
      compatibility principle may be used as a general design guideline for scrolling
      and (b) a consistent scrolling method should be available on various operating
      systems.

PMID- 24745204
TI  - Improving the driver-automation interaction: an approach using automation
      uncertainty.
AB  - OBJECTIVE: The aim of this study was to evaluate whether communicating automation
      uncertainty improves the driver-automation interaction. BACKGROUND: A false
      system understanding of infallibility may provoke automation misuse and can lead
      to severe consequences in case of automation failure. The presentation of
      automation uncertainty may prevent this false system understanding and, as was
      shown by previous studies, may have numerous benefits. Few studies, however, have
      clearly shown the potential of communicating uncertainty information in driving.
      The current study fills this gap. METHOD: We conducted a driving simulator
      experiment, varying the presented uncertainty information between participants
      (no uncertainty information vs. uncertainty information) and the automation
      reliability (high vs.low) within participants. Participants interacted with a
      highly automated driving system while engaging in secondary tasks and were
      required to cooperate with the automation to drive safely. RESULTS: Quantile
      regressions and multilevel modeling showed that the presentation of uncertainty
      information increases the time to collision in the case of automation failure.
      Furthermore, the data indicated improved situation awareness and better knowledge
      of fallibility for the experimental group. Consequently, the automation with the
      uncertainty symbol received higher trust ratings and increased acceptance.
      CONCLUSION: The presentation of automation uncertaintythrough a symbol improves
      overall driver-automation cooperation. APPLICATION: Most automated systems in
      driving could benefit from displaying reliability information. This display might
      improve the acceptance of fallible systems and further enhances driver-automation
      cooperation.

PMID- 24745205
TI  - Exotic optoelectronic properties of organic semiconductors with super-controlled
      nanoscale sizes and molecular shapes.
AB  - We present several aspects of thiophene/phenylene co-oligomers (TPCOs). TPCOs are
      regarded as a newly occurring class of organic semiconductors. These materials
      are synthesized by hybridizing thiophene and phenylene rings at the molecular
      level with their various mutual arrangements. These materials are characterized
      by the super-controlled nanoscale sizes and molecular shapes. These produce
      peculiar crystallographic structures and high-performance optical and electronic
      properties. The crystals of TPCOs were obtained through both vapor phase and
      liquid phase. In the TPCO crystals, the molecules take upright configuration.
      These cause large carrier mobilities of field-effect transistors and laser
      oscillations under optical excitations. Spectrally-narrowed emissions (SNEs) were
      also achieved under weak optical excitation using a mercury lamp. The light
      emitting field-effect transistors using these crystals for an active layer have
      shown the current-injected SNEs when the device was combined with an optical
      cavity and operated by an alternating-current gate-voltage method. Thus the TPCO
      materials will play an important role in the future in the fields of nanoscale
      technology and organic semiconductor materials as well as their optoelectronic
      device applications.

PMID- 24745206
TI  - Designed nanostructures of clay for controlled adsorption of organic compounds.
AB  - The utilization of smectite clay, swelling layered silicate, as scaffolds for
      designing functional nanostructures was overviewed. Surface modification of
      smectites with organoammonium ions has given hydrophobic and microporous nature
      to uptake nonionic organic contaminants from environments. The states of the
      adsorbed nonionic organic compounds have been altered and varied by the
      modification of smectites as shown by the controlled release and specific
      catalytic reactions. Cationic species have been easily concentrated on smectites
      from aqueous phase and the states (orientation and distribution) have been
      controlled by the co-adsorption of both cationic and nonionic species. The
      functions of smectite-organic intercalation compounds derived from the precisely
      controlled nanostructures were introduced in this review.

PMID- 24745207
TI  - Functionalization of layered titanates.
AB  - This review article describes the synthesis, modification, and function of
      lepidocrocite-type layered titanate (A(x)Ti(2-y)M(y)O4, A: A, interlayer cation;
      M, metal or vacancy). Due to the compositional variation, which affects cation
      exchange, semiconducting and swelling properties, lepidocrocite-type layered
      titanates have attracted increasing attention in solid-state materials chemistry.
      The immobilization of functional units has been done to improve the properties as
      well as to impart additional functions. Here, we highlight recent developments of
      hybrid materials derived from the intercalation of inorganic and organic cations,
      organic functional groups, and nanoparticles into lepidocrocite-type layered
      titanates.

PMID- 24745208
TI  - Semiconductor quantum dots for future optical applications.
AB  - Research and development of the semiconductor quantum dots (QDs) for optical
      applications are reviewed. The QDs are small crystals composed of ILL-V, II-VI,
      IV and IV-VI semiconductors, the size of which is about 10 nm. They are
      categorized into two groups. One is called the self-assembled QDs which are grown
      epitaxially on the semiconductor substrate, and the other is the colloidal QDs
      synthesized in the solvent using chemical technique. Since the emission
      wavelength of both QDs covers wide range, i.e., from visible to infrared, the QDs
      are attractive to various application fields. In this article, we focus on the
      progress in the three application fields, i.e., the replacement of existing
      products, the quantum information devices, and the solar cells.

PMID- 24745209
TI  - Recent advances in the fabrication of nanostructured barrier films.
AB  - The fabrication of barrier packaging films has gained significant momentum in
      recent years. Besides its dominance in the food industry as a means to extend the
      shelf-life of perishable goods and facilitate ease of handling and
      transportation, the use of barrier films to protect semiconductor and flexible
      electronics from dust, oxidation and moisture has generated considerable interest
      in recent years. This has ushered in new challenges for researchers to design and
      develop novel thin film barrier coatings that could be made available at a
      fraction of the cost. The emergence of the multidisciplinary field of
      nanotechnology has provided innovative solutions in the fields of medicine,
      catalysis and energy. In this review, we will be examining the integration of
      nanoscience driven techniques with barrier film technology with applications in
      both food and electronics industry. Details regarding permeation theory, some key
      parameters governing gas/moisture barrier properties and the market potential of
      nanostructured barrier films have been included. This review also explores
      several past and current examples of successful inclusion of functional
      nanostructured or colloidal materials to fabricate tailor-made barrier films.
      Finally a brief discussion regarding novel emerging trends for this industry has
      been included.

PMID- 24745210
TI  - Recent progress in the applications of layer-by-layer assembly to the preparation
      of nanostructured ion-rejecting water purification membranes.
AB  - Reverse osmosis (RO) and nanofiltration (NF) are the two dominant membrane
      separation processes responsible for ion rejection. While RO is highly efficient
      in removal of ions it needs a high operating pressure and offers very low
      selectivity between ions. Nanofiltration on the other hand has a comparatively
      low operating pressure and most commercial membranes offer selectivity in terms
      of ion rejection. However in many nanofiltration operations rejection of
      monovalent ions is not appreciable. Therefore a high flux high rejection membrane
      is needed that can be applied to water purification systems. One such alternative
      is the usage of polyelectrolyte multilayer membranes that are prepared by the
      deposition of alternately charged polyelectrolytes via layer-by-layer (LbL)
      assembly method. LbL is one of the most common self-assembly techniques and finds
      application in various areas. It has a number of tunable parameters like
      deposition conditions, number of bilayers deposited etc. which can be manipulated
      as per the type of application. This technique can be applied to make a nanothin
      membrane skin which gives high rejection and at the same time allow a high water
      flux across it. Several research groups have applied this highly versatile
      technique to prepare membranes that can be employed for water purification. Some
      of these membranes have shown better performance than the commercial
      nanofiltration and reverse osmosis membranes. These membranes have the potential
      to be applied to various different aspects of water treatment like water
      softening, desalination and recovery of certain ions. Besides the conventional
      method of LbL technique other alternative methods have also been suggested that
      can make the technique fast, more efficient and thereby make it more commercially
      acceptable.

PMID- 24745211
TI  - Characterization of magnetic and dielectric properties of Bi(1-x)Gd(x)FeO3
      nanoparticles by local structure analyses.
AB  - Bi(1-x)Gd(x)FeO3 (0 < or = x < or = 1.0) nanoparticles were synthesized by a wet
      chemical method. The annealing temperatures were controlled to obtain single
      phase Bi(1-x)Gd(x)FeO3 nanoparticles. The crystal diameters decreased as the
      number of doped Gd ions increased. The crystal structure changed, as the number
      of Gd ions increased, from rhombohedral to orthorhombic perovskite, at x = 0.2.
      The behavior of the magnetization curves observed at various values of x (x =
      0.05, 0.1, 0.15) of the rhombohedral structure suggested that the canted
      antiferromagnetism and remanent magnetization (M(r)) drastically increased,
      compared with those at x = 0 (BiFeO3). It is suggested that the spin-canting
      angle of the Fe ions increased with the increase in the number of Gd ions. The
      dielectric properties at x = 0.1 showed that the dielectric loss (tan delta) was
      improved, compared with that at x = 0 (BiFeO3), by approximately 90%, while the
      real part of the dielectric constant epsilon' was reduced by approximately 15%.
      The reason is that the doping impurities restrained the reduction in the leakage
      current. It was found, from the X-ray absorption fine structure (XAFS) spectra,
      that Gd ions were doped accurately and that the symmetry of the B site was
      improved. The Mossbauer analysis suggested the existence of magnetic cycloid
      spiral ordering.

PMID- 24745212
TI  - Sodium dodecylsulfate bilayer formation under a cationic surfactant Langmuir
      monolayer at the air-water interface.
AB  - An aqueous solution of sodium dodecylsulfate (SDS) was injected into a Langmuir
      monolayer of dioctadecyldimethylammonium chloride (DODAC) at the air-water
      interface. Infrared external spectra, atomic force microscopy (AFM), and quartz
      crystal microbalance (QCM) measurements revealed that the resulting surface
      monolayer was a multilayer structure consisting of a DODAC monolayer as the upper
      layer and an SDS bilayer as the underlayer. Furthermore, the SDS alkyl chain was
      in the all-trans conformation, and the molecular packing of the DODAC alkyl
      chains was hexagonal with the trans-zigzag plane of the methylene chain oriented
      randomly around the chain axis. We also discuss the structure of the multilayer
      obtained by injecting SDS into a mixed Langmuir monolayer of DODAC + SDS.

PMID- 24745213
TI  - Reductant-free colloidal synthesis of near-IR emitting germanium nanocrystals:
      role of primary amine.
AB  - High temperature colloidal synthesis without using hazardous reducing agent is
      demonstrated here to develop a straight forward pathway for synthesizing near-IR
      (NIR) light emitting germanium nanocrystals (Ge NCs). The NCs were prepared by
      heating a mixture of germanium (II) iodide and organoamine. This article presents
      an important role of the primary amine which serves as a reducing agent as well
      as an inhibitor against oxidation by comparing with the tertiary amine.
      Interestingly, the difference in chemical reactivity between each amine causes
      the difference in major structural phase of the products. An efficient route to
      produce NIR light emitting Ge NCs is demonstrated.

PMID- 24745214
TI  - Thermodynamic self-assembly of two-dimensional pi-conjugated metal-porphyrin
      covalent organic frameworks by "on-site" equilibrium polymerization.
AB  - Two-dimensional pi-conjugated metal-porphyrin covalent organic frameworks were
      produced in aqueous solution on an iodine-modified Au(111) surface by "on-site"
      azomethine coupling of Fe(III)-5,10,15,20-tetrakis(4-aminophenyl)porphyrin
      (FeTAPP) with terephthal dicarboxaldehyde and investigated in detail using in
      situ scanning tunneling microscopy. Mixed covalent organic porphyrin frameworks
      consisting of FeTAPP and metal-free TAPP (H2TAPP) were prepared through
      simultaneous adsorption in a mixed solution as well as partial replacement of
      FeTAPP by H2TAPP in an as-prepared metal-porphyrin framework. In the mixed
      framework, the relative distribution of FeTAPP to H2TAPP was not random and
      revealed a preference for homo-connection rather than heteroconnection. The
      construction of substrate-supported, pi-conjugated covalent frameworks from
      multiple building blocks, including metal centers, will be of significant utility
      in the design of functional molecular nanoarchitectures.

PMID- 24745215
TI  - Zirconia nanocolloids having a nanospace of poly(cyclodextrin): preparation and
      application to liquid crystal devices.
AB  - Poly(gamma-cyclodextrin) (PgammaCyD)-protected ZrO2 nanocolloids were prepared by
      using a microwave reactor equipped with ultrasonic nozzle mixing at 240 degrees C
      for 30 min in a tetraethylene glycol solution of zirconium (IV) ethoxide in the
      presence of poly(gamma-cyclodextrin). Particles in PgammaCyD-protected ZrO2
      nanocolloids have an average diameter of 7.2 nm and mainly distribute within the
      range of about 3 to 10 nm. The nanocolloids were dispersed in 4'-pentylbiphenyl-4
      carbonitrile (5CB) and practical liquid crystal to construct novel twisted
      nematic liquid crystal devices (TN-LCDs). The response time of this TN-LCDs in
      the presence of PgammaCyD-protected ZrO2 nanocolloids was faster than that in the
      absence. The threshold voltage of TN-LCDs by doping PgammaCyD-protected ZrO2
      nanocolloids decreased. The decrease of threshold voltage can reduce power
      consumption, which may meet the demands of future power-saving LCDs.

PMID- 24745216
TI  - Visible-light-induced photocatalysis of 2D-hexagonal mesoporous SiO2-TiO2
      deposited with Au nanoparticles.
AB  - Au nanoparticles (NPs) are deposited using a couple of methods onto a sol-gel
      derived mesoporous SiO2-TiO2 template. A modification of the template with 3
      aminopropyltriethoxysilane (APTES) before the deposition of Au leads to the
      formation of Au nanorods instead of Au nanospheres in the tubular mesopores. The
      modification also causes a deterioration of visible-light-induced photocatalytic
      activity. Heat treatment of this sample to remove APTES results in an
      amelioration of the photocatalytic activity. The detailed mechanism of the
      deterioration and amelioration of the activity is discussed on the accessibility
      of the reactant to the sample and the easiness of the charge carrier transfer
      between TiO2 and Au NPs.

PMID- 24745217
TI  - Halogen- and acid-free syntheses of TiO2 nanocrystal coatings and high surface
      area TiO2 nanocrystal-assembled particles.
AB  - Halogen- and acid-free aqueous solutions were developed to synthesize TiO2
      nanocrystal coatings and high surface area TiO2 nanocrystal-assembled particles.
      Fluorine doped tin oxide substrates were covered with TiO2 nanocrystal coatings
      in the solutions containing titanium(IV) potassium oxalate, 2-hydrate
      (K2[TiO(C2O4)2] x 2H2O) at 90 degrees C for 3 days. The substrates changed color
      by the coatings. The nanocrystals were about 10-50 nm in size. They connected
      with the substrates strongly due to direct nucleation and crystallization on the
      substrates. Furthemore, TiO2 particles were synthesized from the solutions at 90
      degrees C for 3 days. They were assemblies of TiO2 nanocrystals. Brunauer-Emmett
      Teller surface area reached to 275 m2/g. Nanospaces were formed by assembly of
      the nanocrysrtals. They contributed high surface area. Halogen- and acid-free
      aqueous solution processes had advantages of low environmental load and safety
      manufacturing environment. Harmless TiO2 coatings and particles can be applied to
      medical applications, medicines, cosmetics, food additives, etc.

PMID- 24745218
TI  - In-situ formation of silver nanoparticles using nonionic surfactant reverse
      micelles as nanoreactors.
AB  - In this paper, we report the one-step synthesis of metallic silver nanoparticles
      (Ag NP) using nonionic surfactant reverse micelle as nanoreactors. Diglycerol
      monolaurate (C12G2) spontaneously self-assemble into spheroid reverse micelles
      having size 10-12 nm in cyclohexane under ambient conditions of temperature and
      pressure. The spheroid C12G2 reverse micelles swell with water. Swollen reverse
      micelles having size - 20 nm are formed upon incorporation of 1% water. We used
      C12G2 reverse micelles as nanoreactors for making ordered nanostructure of Ag-NP
      by replacing water with aqueous silver nitrate solution. The diglycerol moiety of
      the surfactant reduces silver ions into metallic silver and thereby stabilizes
      the generated Ag NP. We found that shape and size of the Ag NP is closely related
      to the structure of nanoreactor. Similar results have been observed in linear
      chain alkane n-octane. We found bigger Ag NP from the C12G2/octane reverse
      micelle system as the size of the micelle in this system is bigger than that of
      the C12G2/cyclohexane system. This simple approach based on in-situ reduction of
      metal ions (without the need of reducing agent) opens a new possibility for the
      development of controlled synthesis of nanostructured noble metallic
      nanoparticles.

PMID- 24745219
TI  - Facile fabrication of silver nanoclusters as promising surface-enhanced Raman
      scattering substrates.
AB  - We present a simple wet chemical method to make thin film of silver nanoclusters
      on glass or silicon substrate. The method includes immersion of glass or silicon
      substrate into a saturated solution of silver nitrate in n-octanol. After 24 h,
      thin film of silver nanoclusters, which are micrometer-scale aggregates of silver
      nanoparticles with average size in the range of 80-100 nm, are formed on the
      substrate. The film is characterized by X-ray diffraction, scanning electron
      microscopy, atomic force microscopy, X-ray photoelectron spectroscopy, and UV-Vis
      spectroscopy. Potential use of the Ag nanoclusters as a surface-enhanced Raman
      scattering based sensing platform is demonstrated by measuring increased Raman
      signals from organic molecule adsorbed on the Ag nanoparticle clusters.

PMID- 24745220
TI  - Water bath synthesis of tin oxide nanostructure coating for a molecular sensor.
AB  - Tin oxide nanostructures were fabricated using a water bath technique. The
      structures were modified with dye-labeled DNAs for a molecular sensor. Sensing
      mechanism of the sensor was based on a photoelectric conversion effect.
      Photoluminescence intensities from the tin oxide nanostructures reached to 16
      times larger than that from SnO2:F films. High photocurrent of 5.5 x 10(-6) A and
      high signal-to-noise ratio of 29 were achieved in this system. Photoelectric
      conversion on a combination of the dye-labeled DNA and the tin oxide was an
      essence of the sensing system. Surface nanospaces were effectively utilized to
      increase photoluminescence and photocurrent.

PMID- 24745221
TI  - Carbon matrix based magnetic nanocomposites for potential biomedical
      applications.
AB  - It was found that by varying the pyrolysis temperature of the polymeric
      precursor, carbon matrix magnetic nanocomposites with different constitution and
      fractions of magnetic component were made. X-ray diffraction, transmission
      electron microscopy and Raman spectroscopy revealed the presence of
      nanocrystallites (NCs) of Co, Fe3C and Ni embedded in porous, partially
      graphitized carbon matrix. Vibrating sample magnetometer measurements enabled to
      determine the correlation between NCs size distribution and magnetic properties.
      The magnetic studies confirmed that the coercivity, saturation and remanent
      magnetizations, as well as fraction of the magnetic component depend on the
      pyrolysis temperature. The Co#C and Fe3C#C composites exhibited ferromagnetic
      behavior with a remanent to saturation magnetization (M(R)/M(S)) ratio ranging
      from 0.25 to 0.3, whereas in the Ni containing samples a relatively small
      M(R)/M(S) ratio point to significant contribution of superparamagnetic
      interactions. As the carbon matrix magnetic nanocomposites are proposed for
      biomedical application the basic cytotoxicity test were performed to evaluate a
      potential toxic effect of the materials on MG-63 cells line.

PMID- 24745222
TI  - Effects of pore structure on the high-performance capacitive deionization using
      chemically activated carbon nanofibers.
AB  - Capacitive deionization (CDI) electrodes were constructed from activated carbon
      fibers prepared using electrospinning and chemical activation. The CDI
      efficiencies of these electrodes were studied as a function of their specific
      surface areas, pore volumes and pore sizes via salt ion adsorption. The specific
      surface areas increased approximately 90 fold and the pore volume also increased
      approximately 26 fold with the use of greater amounts of the chemical activation
      agent. There was a relative increase in the mesopore fraction with higher
      porosity. A NaCI solution was passed through a prepared CDI system, and the salt
      removal efficiency of the CDI system was determined by the separation of the Na+
      and Cl- ions toward the anode and cathode. The CDI efficiency increased with
      greater specific surface areas and pore volumes. In addition, the efficiency per
      unit pore volume increased with a reduction in the micropore fraction, resulting
      in the suppressed overlapping effect. In conclusion, the obtained improvements in
      CDI efficiency were mainly attributed to mesopores, but the micropores also
      played an important role in the high-performance CDI under conditions of high
      applied potential and high ion concentrations.

PMID- 24745223
TI  - Electrical resistance behavior of oxyfluorinated graphene under oxidizing and
      reducing gas exposure.
AB  - The electrical resistance behavior of graphene was studied under oxidizing and
      reducing gas exposure. The graphene surface was modified via oxyfluorination to
      obtain a specific surface area and oxygen functional groups. Fluorine radicals
      provided improved pore structure and introduction of an oxygen functional group.
      A high-performance gas sensor was obtained based on enlarged target gas
      adsorption sites and an enhanced electron charge transfer between the target gas
      and carbon surface via improved pore structure and the introduction of oxygen
      functional groups, respectively.

PMID- 24745224
TI  - Active site nanospace of aminoacyl tRNA synthetase: difference between the class
      I and class II synthetases.
AB  - The present work is aimed at understanding the origin of the difference in the
      molecular organization of the active site nanospaces of the class I and class II
      aminoacyl tRNA synthetases (aaRSs) which are tunnel-like structures. The active
      site encloses the cognate amino acid (AA) and the adenosine triphosphate (ATP) to
      carry out aminoacylation reaction. Comparison of the structures of the active
      site of the class I and class II (aaRSs) shows that the nanodimensional tunnels
      are curved in opposite directions in the two classes. We investigated the origin
      of this difference using quantum mechanical computation of electrostatic
      potential (ESP) of substrates, surrounding residues and ions, using Atoms in
      Molecule (AIM) Theory and charge population analysis. We show that the difference
      is principally due to the variation in the spatial charge distribution of ATP in
      the two classes which correspond to extended and bent conformations of ATP. The
      present computation shows that the most feasible pathway for nucleophilic attack
      to alphaP is oppositely directed for class I and class II aaRSs. The available
      crystal structures show that the cognate AA is indeed located along the channel
      favorable for nucleophilic attack as predicted by the ESP analysis. It is also
      shown that the direction of the channel changes its orientation when the
      orientation of ATP is changed from extended to a bent like structure. We further
      used the AIM theory to confirm the direction of the approach of AA in each case
      and the results corroborate the results from the ESP analysis. The opposite
      curvatures of the active site nanospaces in class I and class II aaRSs are
      related with the influence of the charge distributions of the extended and bent
      conformations of ATP, respectively. The results of the computation of
      electrostatic potential by successive addition of active site residues show that
      their roles on the reaction are similar in both classes despite the difference in
      the organization of the active sites of class I and class II aaRSs. The
      difference in mechanism in two classes as pointed out in recent study (S. Dutta
      Banik and N. Nandi, J. Biomol. Struct. Dyn. 30, 701 (2012)) is related with the
      fact that the relative arrangement of the ATP with respect to the AA is opposite
      in class I and class II aaRSs as explained in the present work. The charge
      population difference between the reacting centers (which are the alphaP atom of
      ATP (q(p)) and the attacking oxygen atom of carboxylic acid group (q(o)),
      respectively) denoted by delta(q), is a measure of the propensity of nucleophilic
      attack. The population analysis of the substrate AA shows that a non-negligible
      difference exists between the attacking oxygens of AA in class I (syn) and in
      class II (anti) which is one reason for the lower value of delta(q) in class II
      relative to class I. The population analysis of the AA, ATP, Mg+2 ions and active
      site residues shows that the difference in delta(q) values of the two classes is
      substantially reduced. When ions and residues are considered. Thus, the bent
      state of ATP, Mg+2 ions and active site residues complements it cognate AA to
      carry out the nucleophilic reaction in class I as efficiently as occurs in class
      I (with the extended state of ATP, single Mg+2 ion and active site residues).
      This could be one reason for the two different conformations of ATP in the two
      classes. The mutual arrangements of AA and ATP in each aaRS are guided by the
      spatial charge distribution of ATP (extended and bent). The present work shows
      that the construction of nanospace complements the arrangement of the substrate
      (AA and ATP).

PMID- 24745225
TI  - Photodegradation of 4-nitrophenol using cadmium sulphide nanoparticles.
AB  - An efficient method to degrade 4-nitrophenol (4-NP) using cadmium sulphide
      nanoparticles (CdS NPs) prepared by a novel method as a photocatalyst in the
      presence of H2O2 as a free radical generator was developed. To investigate the
      degradation mechanism, the interaction between the substrate (4-NP) and the
      catalyst (CdS NPs) was studied using UV-visible absorption and emission spectral
      techniques. Investigation on the effect of pH of the medium on the degradability
      of 4-NP revealed that neither the acidic (pH 4) nor alkaline (pH 9) is as
      suitable as pH 6 due to the desorption of 4-NP from the catalyst surface at the
      former condition and the existence of 4-NP in its most stable quinonoid form at
      the latter pH. Similarly, the effect of ratio between the photocatalyst (CdS NPs)
      and the substrate (4-NP) was also investigated to achieve higher efficiency in
      the photocatalytic reaction.

PMID- 24745226
TI  - Detail study on ac-dc magnetic and dye absorption properties of Fe3O4 hollow
      spheres for biological and industrial application.
AB  - Here solvo-thermal technique has been used to synthesize hollow-nanospheres of
      magnetite. We have shown that PVP plays an important role to control the particle
      size and also helps the particles to take the shape of hollow spheres. Structural
      analysis was done by XRD measurement and morphological measurements like SEM and
      TEM were performed to confirm the hollow type spherical particles formation and
      their shape and sizes were also investigated. The detail ac-dc magnetic
      measurements give an idea about the application of these nano spheres for
      hyperthermia therapy and spontaneous dye adsorption properties (Gibbs free energy
      deltaG0 = -0.526 kJ/mol for Eosin and -1.832 kJ/mol for MB) of these particles
      indicate its use in dye manufacturing company. Being hollow in structure and
      magnetic in nature such materials will also be useful in other application fields
      like in drug delivery, arsenic and heavy metal removal by adsorption technique,
      magnetic separation etc.

PMID- 24745227
TI  - Effect of Ce doping on structural, optical and photocatalytic properties of ZnO
      nano-structures.
AB  - A novel self-assembled pure and Ce doped ZnO nano-particles (NPs) were
      successfully synthesized by a simple low temperature co-precipitation method. The
      prepared photocatalysts were characterized by X-ray diffraction (XRD), High
      resolution scanning electron microscopy (HR-SEM), High resolution transmission
      electron microscopy (HR-TEM), diffuse reflectance spectroscopy (DRS) and
      Photoluminescence (PL) spectroscopy. The results indicated that the prepared
      photocatalysts shows a novel morphology, high crystallinity, uniform size
      distribution, and more defects. Photocatalytic degradation (PCD) of nonylphenol,
      a potent endocrine disrupting chemical in aqueous medium was investigated. Higher
      amount of oxygen defects exhibits enhanced PCD of nonylphenol. In addition, the
      influence of the Ce contents on the structure, morphology, absorption, emission
      and photocatalytic activity of ZnO nanoparticles (NPs) were investigated
      systematically. The relative PCD efficiency of pure ZnO, Ce-doped ZnO NPs and
      commercial TiO2 (Degussa P-25) have also been discussed.

PMID- 24745228
TI  - Thermal performance of ethylene glycol based nanofluids in an electronic heat
      sink.
AB  - Heat transfer in electronic devices such as micro processors and power converters
      is much essential to keep these devices cool for the better functioning of the
      systems. Air cooled heat sinks are not able to remove the high heat flux produced
      by the today's electronic components. Liquids work better than air in removing
      heat. Thermal conductivity which is the most essential property of any heat
      transfer fluid can be enhanced by adding nano scale solid particles which possess
      higher thermal conductivity than the liquids. In this work the convective heat
      transfer and pressure drop characteristics of the water/ethylene glycol mixture
      based nanofluids consisting of Al2O3, CuO nanoparticles with a volume
      concentration of 0.1% are studied experimentally in a rectangular channel heat
      sink. The nano particles are characterized using Scanning Electron Microscope and
      the nannofluids are prepared by using an ultrasonic vibrator and Sodium Lauryl
      Salt surfactant. The experimental results showed that nanofluids of 0.1% volume
      concentration give higher convective heat transfer coefficient values than the
      plain water/ethylene glycol mixture which is prepared in the volume ratio of
      70:30. There is no much penalty in the pressure drop values due to the inclusion
      of nano particles in the water/ethylene glycol mixture.

PMID- 24745229
TI  - P2O5 assisted green synthesis of multicolor fluorescent water soluble carbon
      dots.
AB  - A low cost synthesis of multicolor fluorescent carbon dots (C-dots) from edible
      sugars is described here. Common sugars like dextrose, lactose or maltose in
      aqueous medium gets dehydrated using phosphorus pentoxide (P2O5). The reaction is
      facile and completed within few minutes to form insoluble carbon (C-dots) mostly
      having the graphitic (G-band, Raman) sp2 hybridized carbon atoms (C-atoms). This
      insoluble carbon on oxidative treatment with nitric acid produced disordered sp3
      (D-band retaining G-band, Raman) hybridized C-atoms, originated from the
      graphitic pool with sp2 hybridized C-atoms. This high density assimilation of
      self passivated "surfacial defects" become emissive during electronic
      transitions. Surfacial defects due to high degree of electrophilic carboxylation
      create the water soluble version of multicolor fluorescent C-dots as "water
      soluble fluorescent carbon dots" (wsFCDs). wsFCDs being itself self-passivated
      imposes the tunable multicolor emission throughout the visible spectrum without
      having any external coating and surface passivation and could be used as
      multicolor fluorescent probe especially in the emerging field of optical bio
      imaging.

PMID- 24745230
TI  - In situ catalytic pyrolysis of miscanthus over modified SBA-15 catalysts using Py
      GC/MS.
AB  - Various SBA-15-based catalysts, Si-SBA-15, Pt/Si-SBA-15, Al-SBA-15, and Pt/Al-SBA
      15, were applied to the catalytic pyrolysis of miscanthus. Pt nanoparticles with
      three different sizes, 1.7 nm, 2.9 nm, and 7.1 nm, were used to synthesize Pt/Si
      SBA-15 and Pt/Al-SBA-15. Pyrolysis-gas chromatography/mass spectrometry was used
      for the pyrolysis experiments. The catalysts were characterized by X-ray
      diffraction patterns, transmittance electron microscopy, N2 adsorption
      desorption, and Brunaure-Emmett-Teller surface area. The product species
      distribution of pyrolysis of miscanthus was significantly affected by the acid
      property of the catalyst and the presence of Pt. In particular, Pt/Al-SBA-15,
      which has both acid sites and Pt, changed the product species distribution to the
      largest extent; the main products were phenolics and furans. The effect of Pt
      particle size on the species distribution of pyrolysis product was negligible.

PMID- 24745231
TI  - Chaotic analysis of the geometrically nonlinear nonlocal elastic single-walled
      carbon nanotubes on elastic medium.
AB  - This paper presents the chaotic analysis of the single-walled carbon nanotubes on
      elastic medium. Due to small scales of the nanotubes, the nonlocal elastic theory
      is applied. Besides, due to large-amplitude vibrations of the nanotubes, the
      geometrical nonlinearity is taken into account, so the von Karman strain is
      incorporated. The results show that the period-three oscillation, the chaos and
      the period-one oscillation are excited by the different excitation amplitudes. In
      addition, the excitation amplitude of the chaos increases as the nonlocal
      parameter increases. These results are also validated by the steady-state time
      responses, the FFT spectrums, the phase portraits, and the Poincare sections.

PMID- 24745232
TI  - Structural characterization and adsorption properties of pluronic F127 onto iron
      oxides magnetic nanoparticles.
AB  - Superparamagnetic iron oxide nanoparticles coated with polymers have shown low
      toxicity and chemical stability in physiological condition, thereby can be used
      to deliver encapsulated drugs throughout the body by external magnetic fields. In
      this study, magnetic nanoparticles were synthesized thorough co-precipitation
      method and their interaction with Pluronic F127 block copolymer as well as
      adsorption properties of polymer onto nanoparticles were investigated. Adsorption
      measurement revealed different adsorption behaviors below and above the polymer's
      critical micelle concentration. The Freundlich isotherm was found to better
      describe the adsorption behavior of Pluronic F127 onto SIONPs particles below the
      block copolymer critical micelle concentration. At higher concentration, the
      adsorbed amount is likely to diminish due to interpenetration of the adsorbed
      macromolecular micelles and volume-excluded effects for block copolymers.
      Furthermore, magnetic nanocomposites with different concentration of polymers
      were prepared through hydrothermal method. The crystalline structure, morphology,
      pore structure, and magnetic properties of magnetic nanoparticles/nanocomposites
      products at different pH and polymer concentration were studied. Results showed
      that due to the hematite impurities, magnetic nanocomposites synthesized at
      higher pH have lower magnetization.

PMID- 24745233
TI  - Heat transfer performance of Al2O3/water nanofluids in a mini channel heat sink.
AB  - The high density heat removal in electronic packaging is a challenging task of
      modern days. Finding compact, energy efficient and cost effective methods of heat
      removal is being the interest of researchers. In the present work, mini channel
      with forced convective heat transfer in simultaneously developing regime is
      investigated as the heat transfer coefficient is inversely proportional to
      hydraulic diameter. Mini channel heat sink is made from the aluminium plate of 30
      mm square with 8 mm thickness. It has 15 mini channel of 0.9 mm width, 1.3 mm
      height and 0.9 mm of pitch. DI water and water based 0.1% and 0.2% volume
      fractions of Al2O3/water nanofluids are used as coolant. The flow rates of the
      coolants are maintained in such a way that it is simultaneously developing.
      Reynolds number is varied from 400 to 1600 and heat input is varied from 40 W to
      70 W. The results showed that heat transfer coefficient is more than the heat
      transfer coefficient of fully developed flow. Also the heat transfer is more for
      nanofluids compared to DI water.

PMID- 24745234
TI  - Fabrication of room-temperature operational single-electron devices using Au
      nanoparticles.
AB  - Au nanoparticles (5-10 nm in diameter) single electron devices (SEDs) were
      fabricated utilizing both electron beam lithography and granular film deposition.
      Both multiple-tunnel junction (MTJ) and double-tunnel junction (DTJ) were
      fabricated by adjusting the number of Au nanoparticles between the electrodes.
      Coulomb blockade effects were clearly observed at room temperature from the MTJs.
      The threshold voltage of the MTJ-SED with a large gap was about 1.5 V, whereas
      that with a small gap was about 0.8 V, respectively. When the gap was below 20
      nm, a periodic Coulomb staircase was observed from the DTJ-SED at room
      temperature, where the charging energy was about 0.114 eV.

PMID- 24745235
TI  - Fabrication of solution processed carbon nanotube embedded polyvinyl alcohol
      composite film for non-volatile memory device.
AB  - Carbon nanotubes (CNTs) were synthesized by chemical vapor deposition using
      nickel coated stainless steel prepared by electrophoretic deposition. CNTs were
      embedded in polyvinyl alcohol (PVA) which acts as an organic insulator to
      fabricate Si/PVA/CNT/PVA/Al Metal-Insulator-Semiconductor type memory devices.
      The effect of CNT content in the charge storage capacity of PVA-CNT composite
      film was investigated. The hysteresis obtained from the capacitance-voltage (CV)
      measurement resulted in a memory window of 1.9 V with 3% CNT loading with the
      gate voltage sweep of +/- 6 V at 1 MHz under room temperature. The memory window
      of the devices was due to electron injection into the CNT charge storage elements
      from the top electrode through PVA. The extensive pi-conjugation along the CNT
      axis traps the electrons in the CNT network. The ON/OFF state current ratio of
      Si/Al/PVA-CNT/AI device with 3% CNT in PVA demonstrated significantly a lower
      turn-on voltage of -1 V and a higher ON/OFF state current ratio of 10(7). The non
      volatile and reprogrammable switching behavior of the device demonstrated the
      characteristic of a rewritable memory.

PMID- 24745236
TI  - Electrochemical analysis of polyethylenimine-modified graphene oxide supports for
      Pt nanoparticles catalyst electrode.
AB  - Polyethylenimine-modified graphene oxide supported platinum electro-catalyst was
      synthesized by a modified sodium borohydride reduction method. As a modifier
      agent, polyethylenimine (PEI) was used to form coating layer onto graphene
      surface. To ascertain the electrochemical behavior, PEI-reduced graphene oxide
      (PEI-RGO) was compared with changing the PEI/RGO weight ratio of 1:0.5, 1:1 and
      1:2, respectively. The morphology of electro-catalysts was observed by
      transmission electron microscope (TEM) and scanning electron microscope (SEM)
      images. In addition, lattice parameters and particle size of electro-catalysts
      were measured by X-ray diffraction (XRD). FT-IR spectra of catalysts were used to
      ascertain existence and functional group of the PEI branches on GO surface.

PMID- 24745237
TI  - Synthesis and electrochemical properties of SnWO4.
AB  - In this paper, a pure SnWO4 was synthesized by solvothermal method. The glucose
      as a carbon sources was mixed with SnWO4 to prepared SnWO4/C composite. The
      structure and morphology were characterized by XRD and SEM techniques. The
      electrochemical properties of SnWO4 and SnWO4/C composite were studied by battery
      comprehensive testing system and AC impedance spectroscopy. The results showed
      that the alpha-SnWO4 phase was formed and its particles were ranged from 50 to
      250 nm. The alpha-SnWO4/C composites behaved higher reversible discharge capacity
      and better cycle performance than that of alpha-SnWO4. The reversible discharge
      capacity of SnWO4/C composites was 780 mA h/g at the current density (50 mA/g)
      and it could keep at 600 mA h/g after 30 cycles. The reason for SnWO4/C composite
      to behave outstanding electrochemical properties was discussed also.

PMID- 24745238
TI  - Laminar heat transfer and friction factor characteristics of carbon nano
      tube/water nanofluids.
AB  - This paper presents an experimental investigation on the convective heat transfer
      and friction factor characteristics of CNT/water nanofluid through a circular
      tube fitted with helical screw tape inserts with constant heat flux under laminar
      flow condition. Nanofluids of 0.1% and 0.2% volume fractions are prepared by two
      step method. Thermo-physical properties like thermal conductivity and viscosity
      are measured by using KD2 thermal property analyzer and Brooke field cone and
      plate viscometer respectively. From the measurements, it is found that the
      viscosity increase is substantially higher than the increase in the thermal
      conductivity. The helical screw tape insets with twist ratios Y = 3, 2.44 and
      1.78 are used to study the convective heat transfer and friction factor
      characteristics under laminar flow in the Reynolds number range of 520-2500. It
      is observed that, in a plain tube, maximum enhancement in Nusselt number for 0.1%
      and 0.2% volume fractions of nanofluids compared to pure water is 15% and 32%
      respectively. With the use of inserts, maximum enhancement in Nusselt number
      corresponding to twist ratios of 1.78, 2.44 and 3 are obtained as 8%, 16% and
      4.6% for 0.1% volume fraction of nanofluid and 5%, 4% and 12% for 0.2% volume
      fraction of nanofluid when compared with water in plain tube. Thermal performance
      factor evaluation revealed that the values at all Reynolds number for all twist
      ratios and both concentration of CNT nanofluid are greater than unity which
      indicates that helical screw tape inserts with twist ratios considered are
      feasible in terms of energy saving in laminar flow.

PMID- 24745239
TI  - Effect of carbon source on the morphology and electrochemical performances of
      LiFePO4/C nanocomposites.
AB  - The carbon coated LiFePO4 (LiFePO4/C) nanocomposites materials were successfully
      synthesized by sol-gel method. The microstructure and morphology of LiFePO4/C
      nanocomposites were characterized by X-ray diffraction, Raman spectroscopy and
      scanning electron microscopy. The results showed that the carbon layers
      decomposed by different dispersant and carbon source had different graphitization
      degree, and the sugar could decompose to form more graphite-like structure
      carbon. The carbon source and heat-treatment temperature had some effect on the
      particle size and morphology, the sample LFP-S700 synthesized by adding sugar as
      carbon source at 700 degrees C had smaller particle size, uniform size
      distribution and spherical shape. The electrochemical behavior of LiFePO4/C
      nanocomposites was analyzed using galvanostatic measurements and cyclic
      voltammetry (CV). The results showed that the sample LFP-S700 had higher
      discharge specific capacities, higher apparent lithium ion diffusion coefficient
      and lower charge transfer resistance. The excellent electrochemical performance
      of sample LFP-S700 could be attributed to its high graphitization degree of
      carbon, smaller particle size and uniform size distribution.

PMID- 24745240
TI  - Conversion of kraft lignin over hierarchical MFI zeolite.
AB  - Catalytic pyrolysis of kraft lignin was carried out using pyrolysis gas
      chromatography/mass spectrometry. Hierarchical mesoporous MFI was used as the
      catalyst and another mesoporous material Al-SBA-15 was also used for comparison.
      The characteristics of mesoporous MFI were analyzed by X-ray diffraction
      patterns, N2 adsorption-desorption isotherms, and temperature programmed
      desorption of NH3. Two catalyst/lignin mass ratios were tested: 5/1 and 10/1.
      Aromatics and alkyl phenolics were the main products of the catalytic pyrolysis
      of lignin over mesoporous MFI. In particular, the yields of mono-aromatics such
      as benzene, toluene, ethylbenzene, and xylene were increased substantially by
      catalytic upgrading. Increase in the catalyst dose enhanced the production of
      aromatics further, which is attributed to decarboxylation, decarbonlyation, and
      aromatization reactions occurring over the acid sites of mesoporous MFI.

PMID- 24745241
TI  - Microwave absorption of sandwich structure based on nanocrystalline SrFe12O19,
      Ni0.5ZnO.5Fe2O4 and alpha-Fe hollow microfibers.
AB  - The microwave absorption properties of sandwich structural absorbers based on the
      nanocrystalline strontium ferrite (SrFe12O19), NiZn ferrite (Ni0.5Zn0.5Fe2O4) and
      alpha-iron (alpha-Fe) hollow microfibers with diameters of 1-3 microm have been
      investigated in the frequency range of 2-18 GHz. The sandwich absorbers composed
      of nanocrystalline ferrite hollow microfibers as the outer or inner layer, and
      the nanocrystalline alpha-Fe hollow microfibers as the interlayer, have strong
      microwave absorption with a broad band and thin thickness. Their microwave
      absorption properties in 2-18 GHz are mainly influenced by the arrangement, each
      layer thickness and total thickness. It finds that the sandwich absorber with 1.6
      mm thick SrFe12O19 microfibers as the outer layer, 0.2 mm thick alpha-Fe
      microfibers as the interlayer and 0.2 mm thick Ni0.5Zn0.5Fe2O4 microfibers as the
      inner layer, exhibits an optimal reflection loss (RL) value of -120.1 dB at 13.2
      GHz and the bandwidth with RL exceeding -10 dB covers 83% of X-band (8.2-12.4
      GHz) and the whole K(u)-band (12.4-18 GHz). This enhancement microwave absorption
      can be attributed to the unique coupling of the nanocrystalline ferrite and alpha
      Fe hollow microfibers arising from the shape anisotropy, interface and small size
      effects.

PMID- 24745242
TI  - Chitosan and chitosan-co-poly(epsilon-caprolactone) grafted multiwalled carbon
      nanotube transducers for vapor sensing.
AB  - Vapor sensitive transducer films consisting of chitosan grafted (CNT-CS) and
      chitosan-co-polycaprolactone grafted (CNT-CS-PCL) multiwalled carbon nanotubes
      were prepared using a spray layer-by-layer technique. The synthesized materials
      (CNT-CS and CNT-CS-PCL) were characterized by Fourier transform infrared
      spectroscopy, 13C CP/MAS solid state nuclear magnetic resonance spectroscopy and
      thermogravimetric analysis. Both CNT-CS and CNT-CS-PCL transducers were analyzed
      for the response of volatile organic compounds and toluene vapors. The ranking of
      the relative resistance (A(r)) for both chitosan based transducers were as
      follows: toluene < chloroform < ethanol < methanol. The CNT transducer (CNT-CS)
      was correlated selectively with an exponential law to the inverse of Flory
      Huggins interaction parameters, chi12. Dosing the films on the interdigitated
      electrodes with methanol, ethanol, chloroform and toluene vapors increased the
      film resistance of CNT-CS but decreased the resistance of CNT-CS-PCL compared to
      that of the reported transducers.

PMID- 24745243
TI  - Distance control of electromigration-induced silver nanogaps.
AB  - Electromigration (EM) in Ag nanocontacts (NCs) was observed in situ on an atomic
      scale using simultaneous measurements of electrical conductance and mechanical
      stress. The in situ observations showed that the critical bias voltage of EM was
      45 mV. As the bias voltage was increased to 100-200 mV, the NCs broke and gaps
      with distances of 1.3 +/- 0.8 nm were obtained for NCs having widths smaller than
      6 nm. When the bias voltage was further increased to 200-300 mV, the gaps
      expanded to more than 3 nm, regardless of the NC width. It was found that the
      nanogap distance could be controlled to fit specific molecular sizes by
      appropriately selecting the bias voltage and NC width.

PMID- 24745244
TI  - Electrical conductivity of single molecular junctions assembled from Co- and Co3C
      encapsulating carbon nanocapsules.
AB  - Single molecular junctions (SMJs) were assembled from cobalt (Co)- and Co carbide
      (Co3C)-encapsulating carbon nanocapsules (CNCs) and two gold electrodes inside a
      high-resolution transmission electron microscope equipped with a specimen
      piezomanipulation system. The structure and electrical transport properties of
      the SMJs were investigated in situ. The current density depended on the perimeter
      of the contact area between CNCs and the electrodes, showing that the current
      flowed not through the encapsulated region but rather along the graphene layers
      of CNCs. It was demonstrated that the properties of graphene can be applied to
      nanodevices using CNCs irrespective of the encapsulating materials.

PMID- 24745245
TI  - Formation and soot combustion of honeycomb-like LaFeO3 microfibers.
AB  - The nanocrystalline, honeycomb-like, perovskite LaFeO3 microfibers with a fibre
      diameter about 1-2 microm and channel sizes about 180-220 nm on the cross-section
      were prepared by the citrate-gel process. These microfibers were characterized by
      X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR),
      scanning electron microscopy (SEM) and Brunauere-Emmette-Teller (BET) method.
      After calcined at a low temperature of 550 degrees C for 6 hours, the single
      phase of perovskite LaFeO3 microfibers is formed and the grain size increases
      from 27 to 38 nm with the calcination temperature increasing from 500 to 650
      degrees C. The catalytic activity for soot combustion was analyzed by thermo
      gravimetric method (TG), and the LaFeO3 microfibers calcined at 600 degrees C
      exhibits the highest catalytic activity for soot combustion, with a lowest T50
      (393 degrees C) and T90 (434 degrees C). The formation mechanism of the honeycomb
      like structure is analyzed and these honeycomb-like microfibers can be used as
      advanced catalysts, absorbents, filters and microreactors.

PMID- 24745246
TI  - Synthesis of novel poly(amidoxime) grafted multiwall carbon nanotube gel and
      uranium adsorption.
AB  - This is the first report on the synthesis of a new functional nanocomposite gel
      containing amidoxime functionalized multiwall carbon nanotube (AO-MWNT-FNC GEL).
      The surface morphology of AO-MWNT-FNC GEL was investigated by field emission
      scanning electron microscopy. The modification of gel with amidoxine groups was
      confirmed by Fourier transform infra red spectroscopy. The AO-MWNT-FNC GEL
      provides effective binding with uranium ions as was ascertained by X-ray
      photoelectron spectroscopy. The AO-MWNT-FNC GEL was utilized as the new adsorbent
      for the recovery of uranium ions from aqueous solution. UV-visible spectroscopy
      was used to monitor the adsorption capacity of the AO-MWNT-FNC GEL toward uranium
      ions. The influence of initial uranium ion concentration and solution pH on the
      adsorption capacity of the AO-MWNT-FNC GEL were studied in batch experiments. The
      new FNC-GEL designed in this study is distinguished by higher adsorption capacity
      for uranium ions due to the synergistic contributions from high surface area of
      MWNT and the functional AO groups in FNC-GEL and exhibits potential for efficient
      recovery of uranium ions.

PMID- 24745247
TI  - Effect of single-wall carbon nanotubes on mechanical property of chondrocytes.
AB  - It is important to elucidate the effects of carbon nanotubes on cell functions
      for their biomedical applications. In this study, the effect of single-walled
      carbon nanotubes (SWCNTs) on the mechanical property of chondrocytes was
      investigated by atomic force microscopy. Chondrocytes were cultured in medium
      containing SWCNTs and showed an increase uptake of SWCNTs with culture time. The
      mechanical property of chondrocytes cultured with or without SWCNTs was measured
      at an indentation depth of 200 nm and 500 nm. The chondrocytes cultured with
      SWCNTs showed higher Young's modulus than that of cells cultured without SWCNTs
      at both indentation depths. The increase became significant after culture for
      more than 3 hours. Indentation at 500 nm depth magnified the change of Young's
      modulus compared to that monitored at 200 nm indentation depth. The results
      indicated uptake of SWCNTs increased the Young's modulus of chondrocytes.

PMID- 24745248
TI  - Electrochemical-signal enhanced information storage device composed of cytochrome
      c/SNP bilayer.
AB  - The films organized with biomolecules and organic materials are important
      elements for developing bioelectronic devices according to their electron
      transfer property. Until now, several concepts of techniques have been
      accomplished to be used for developing biomemory devices. However it is difficult
      to detect the current signal from the electron transfer between biomolecules and
      the substrate in these fabricated films. To enhance the current signal, the
      silver nanoparticle was introduced to the cytochrome c in this present study. The
      surface morphology of the fabricated film was investigated by atomic force
      microscopy. The current signal enhancement was investigated by cyclic
      voltammetry. As a result, we could obtain the redox potentials. Moreover, by
      chronoamperometry, we validated that this proposed layer showed the signal
      enhanced memory property for biomemory devices. This new film composed of the
      cytochrome c and the silver nanoparticle showed the signal enhancement. Using
      chronoamperometry, the areas under the graphs between 0 s and 50 ms were
      calculated. The calculated result showed that the areas under the cytochrome
      c/SNP graph and cytochrome c graph were 6.93 x 10(-7) C and 4.54 x 10(-7) C,
      respectively. This numerical value verified that the cytochrome c/silver
      nanoparticle hetero-layer film showed better electron charged biomemory
      performance compared to the cytochrome c monolayer. This signal-enhanced film can
      be applied to the bioelectronic devices which are able to replace existing
      electronic devices in the near future.

PMID- 24745249
TI  - Electrochemical characterization of graphene-Co3O4 composite electrode in organic
      electrolyte solution containing sulfur.
AB  - In this study, we present an electrochemically improved electrode by using
      graphene-metal oxide composite materials, having a high specific surface area and
      high current density. The morphological and micro-structure properties were
      investigated by field-emission scanning electron microscopy system (FE-SEM),
      transmission electron microscopy (TEM), and X-ray diffractometer (XRD). The
      electrochemical behaviors were investigated by cyclic voltammetry (CV). The
      prepared samples having Co3O4 particles on GNS provided the enhanced
      electrochemical reaction sites and ion-intercalation spots, which were accessible
      to supporting electrolyte ion effectively. We could confirm that GNS-Co3O4
      composite electrode had the superior electrochemical activity than other
      comparative samples.

PMID- 24745250
TI  - Simple and easy DNA mapping method using peptide nucleic acid (PNA) tagging.
AB  - In this paper, we introduce a simple and easy DNA mapping method using peptide
      nucleic acid (PNA) on glass cover-slips based on optical detection. PNA and glass
      cover-slips were used as easy tagging and stretching method, separately. The PNA
      can be invaded lambda (A) DNA at the sequences we wished to tag without any
      additional materials. Alexa-488 fluorophore-conjugated PNA was designed to invade
      at four sites (sequence: AAGAAGAA) of lambda DNA with robust and exact binding.
      Fluorophore tagged lambda DNA was stretched in electrical layer coated glass
      cover-slips. The lambda DNA was stretched as 9.2 um in length. It is
      approximately 60% of theoretical length of lambda DNA and sufficient length to
      promise optical resolution. The sites of desired sequence tagged by PNA were well
      detected in stretched lambda DNA.

PMID- 24745251
TI  - The atomic configuration of graphene/vanadium carbide interfaces in vanadium
      carbide-encapsulating carbon nanocapsules.
AB  - Carbon nanocapsules (CNCs) encapsulating vanadium carbide (VC) nanocrystals with
      a NaCI structure were synthesized by a gas-evaporation method using arc-discharge
      heating. The CNCs were observed by high-resolution transmission electron
      microscopy. The VC nanocrystals within the nanospaces of CNCs were truncated by
      low-index facets and were coated with several graphene layers, forming
      graphene/VC interfaces. The atomic configuration and interlayer spacings at the
      interfaces were found.

PMID- 24745252
TI  - Cellular uptake of single-walled carbon nanotubes in 3D extracellular matrix
      mimetic composite collagen hydrogels.
AB  - Carbon nanotubes (CNTs) exhibit intrinsic unique physical and chemical properties
      that make them attractive candidates for biological and biomedicine applications.
      An efficient cellular uptake of CNTs is vital for many of these applications.
      However, most of the cellular uptake studies have been performed with a two
      dimensional cell culture system. In this study, cellular uptake of single-walled
      carbon nanotubes (SWCNTs) was investigated by using a three-dimensional cell
      culture system. Bovine articular chondrocytes cultured in SWCNTs/collagen
      composite hydrogels maintained their proliferation capacity when compared to the
      culture in collagen hydrogels. Ultraviolet-visible-near-infrared spectroscopy
      analysis revealed a high amount of SWCNTs were internalized by cells. Confocal
      Raman imaging showed that most of the internalized SWCNTs were distributed in the
      perinuclear region. The results indicated that SWCNTs could be internalized by
      chondrocytes when SWCNTs were incorporated in the three-dimensional biomimetic
      collagen hydrogels.

PMID- 24745253
TI  - Crystal dimension of ZSM-5 influences on para selective disproportionation of
      ethylbenzene.
AB  - Crystal size and crystal dimensions are vital role in shape selective feature.
      Para selective disproportionation of EthylBenzene (Dip-EB) was investigated over
      ZSM-5 synthesized in acidic medium. The catalysts were prepared by hydrothermal
      process with various Si/Al ratios (50, 75 and 100) using fluoride ion precursor.
      This fluoride ion precursor dissolves the ZSM-5 nutrients below it neutral pH
      between 4 and 6. The synthesized material was subjected into various physico
      chemical characterizations such as XRD, SEM, TGA and BET analyses. The XRD
      patterns showed high crystalline nature and their resulting SEM images were also
      indicate thin prismatic crystals of large dimension compared with alkaline medium
      synthesized one. The BET results earned good textural property. Catalytic
      activity of vapor phase Dip-EB was carried out between 523 and 673 K. As their
      result, diethylbenzene (DEB) isomers were obtained, but para selective
      Diethylbenzene (p-DEB) was observed higher than others. The high selectivity
      towards p-DEB was due to large crystal dimension of ZSM-5 catalysts synthesized
      in fluoride medium. Hence it is good commercial application for petrochemical
      feed stock production.

PMID- 24745254
TI  - Graphene sheets modified with polyindole for electro-chemical detection of
      dopamine.
AB  - Oxidized polyindole is coated over graphene surface by in-situ chemical oxidation
      method in dilute hydrochloric acid solution. Morphology of graphene modified with
      oxidized polyindole is investigated by scanning electron microscope. The
      interaction of graphene to polyindole is observed by Raman spectroscopy. The
      introduction of carboxylate functionality is observed in graphene due to
      pyrolysis. The association of this functionality with indole monomer and their
      interactive behaviour led to formation of uniform polyindole over graphene
      surface in presence of oxidizing agent. Our chemical synthesis results not only
      formation of uniform polymer thin layer over the graphene sheets but also
      enhances various properties and processibility of the graphene. Negative surface
      charge on the composite material is observed at acidic pH, which shows potential
      for accumulation of positively charged species in the solution. Further it is
      explored for electro-catalytic and sensing applications and shows cation
      permselective behavior of dopamine hydrochloride. It is demonstrated by
      differential pulse voltammetric technique in dopamine concentration range from 10
      microM to 1 mM (in presence of 1 mM ascorbic acid).

PMID- 24745255
TI  - Comparative investigation of structural, optical properties and dye-sensitized
      solar cell applications of ZnO nanostructures.
AB  - Dye-sensitized solar cells (DSSCs) based on ZnO nanostructures with two different
      morphologies, such as nanowires (ZNWs) and nanoparticles (ZNPs), were synthesized
      by microwave combustion (MCM) and conventional combustion (CCM) method. The
      obtained ZnO nanostructures were characterized by X-ray diffraction (XRD), high
      resolution scanning electron microscopy (HR-SEM), high resolution transmission
      electron microscopy (HR-TEM), energy dispersive X-ray analysis (EDX), diffuse
      reflectance (DRS) and photoluminescence (PL) spectroscopy. The XRD results
      confirmed the formation of hexagonal wurtzite ZnO. The crystallite size of the
      ZnO nanostructures was calculated using Sherrer's formula. The formation of ZNWs
      and ZNPs was confirmed by HR-SEM and HR-TEM. The optical absorption and PL
      emissions were determined by DRS and PL spectra respectively. ZnO nanostructures
      with band gap energies of 3.36 eV (MCM) and 3.25 eV (CCM) were obtained. The dye
      sensitized ZnO nanowire arrays exhibit much stronger optical absorption as
      compared with ZnO nanoparticle arrays, suggesting that the larger surface area
      improves light harvesting. The dye-sensitized solar cell based on the optimized
      ZnO nanowires array reaches a conversion efficiency of 1.73%, which is higher
      than that obtained from ZnO nanoparticles (0.69%) under the light radiation of
      1000 W/m2. As-prepared ZNWs have potential applications in fabricating next
      generation nanodevices.

PMID- 24745256
TI  - Alkylated fullerene derivatives for solution-processable organic thin-film
      transistors and bulkheterojunction solar cells.
AB  - In this paper, we report synthesis and characterization of alkylated fullerene
      derivatives for solution-processable organic thin film transistors and solar
      cells. Their physical, thermal, and semiconducting properties have been studied.
      Organic thin-film transistors fabricated from C60TH-Oc exhibit electron
      mobilities as high as 3.2 x 10(-2) cm2 V(-1) s(-1) with 32 V of a threshold
      voltage. The best power conversion efficiency (PCE) was observed in a layered
      structure P3HT:C60TH-Oc (PCE = 0.44%), which was a twice value of P3HT:C60TH-Dd
      (PCE = 0.23%).

PMID- 24745257
TI  - Effective supergrowth of vertical aligned carbon nanotubes at low temperature and
      pressure.
AB  - We present the generalised supergrowth of single and double walled carbon
      nanotubes like "water assisted supergrowth" at low temperature (630 degrees C)
      and pressure (1 Torr) by chemical vapour deposition using various thicknesses of
      iron supported alumina substrate as a catalyst. Reduced temperature and low
      pressure synthesis of single walled (SW) and double walled (DW) carbon nanotubes
      is of interest for their efficient growth into device architectures. Pure SW with
      2.5 nm diameter are obtained with 0.37 nm Fe catalyst at 630 degrees C. We
      demonstrated the decrease of the density versus temperatures and also obtained
      high density materials (1.4 x 10(12) cm(-2)) at low temperature (580 degrees C).
      Scanning and transmission electron microscope studies provided information on the
      height, density of the carpets and the structure and diameter of SW and DW carbon
      nanotubes, respectively.

PMID- 24745258
TI  - Removal of NO(x) at low temperature over mesoporous alpha-Mn2O3 catalyst.
AB  - Low-temperature selective catalytic reduction was carried out over various kinds
      of manganese oxide (MnOx) catalysts. Mesoporous alpha-Mn2O3, commercial bulk
      Mn2O3, and Mn/SBA-15 were used as the catalyst. The NOx removal performances of
      the catalysts were compared. Three different amounts of Mn (5, 10, and 15 wt%)
      were impregnated on SBA-15 to synthesize Mn/SBA-15. The physical and chemical
      properties of the catalysts were examined by Brunauer-Emmett-Teller, X-ray
      diffraction, X-ray photoelectron spectroscopy, and H2-temperature programmed
      reduction analyses. Of all catalysts examined, mesoporous alpha-Mn2O3 exhibited
      the highest low-temperature SCR de-NOx efficiency, reaching about 90% at 175
      degrees C. This is attributed to strong reducing ability and high oxygen mobility
      of mesoporous alpha-Mn2O3 and well dispersed Mn2O3 in its mesoporous framework.

PMID- 24745259
TI  - Ferromagnetic behaviour of anthropogenic multi-walled carbon nanotubes trapped in
      spider web indoor.
AB  - Black carbon (BC) (as partly burnt black particulate matter) present indoor are
      deposited on interior surfaces of the indoors (easily visualize over the blades
      of electric fan/exhausts and over domestic spider webs) are known to be a
      potential indoor pollution problem. We detect with the help of indoor spider webs
      the floating BC contains a significant amount of defective multiwalled carbon
      nanotubes (MWCNTs) possessing room temperature ferromagnetism. Microscopic
      studies shows a lot of internal and surfacial defects in these indoor-MWCNTs.
      Electron paramagnetic resonance (EPR) showed the presence of very stable carbon
      centred radicals in these indoor-MWCNTs. Room temperature ferromagnetism most
      importantly originated by the presence of a large amount of unpaired spin
      frustrated carbon centred radicals (trapped in defects, junctions and fractures)
      which are inadvertently formed during the pyrolysis of carbonaceous materials
      through routine domestic activities.

PMID- 24745260
TI  - Facile synthesis and photoluminescence of near-infrared-emitting CdTe(x)Se(1-x)
      and CdTe(x)Se(1-x)/Cd(y)Zn(-1-y)S quantum dots.
AB  - High-quality colloidal photoluminescent (PL) CdTe(x)Se(1-x) quantum dots (QDs)
      with gradient distribution of components, consisting of Te-rich inner cores and
      Se-rich outer shells, were synthesized via a facile organic method using stearic
      acid as a capping agent. The transmission electron microscopy observation and X
      ray diffraction analysis indicated that the CdTe(x)Se(1-x) QDs revealed a "dot"
      shaped morphology and exhibited a zinc-blende structure which located between
      those of bulk CdTe and CdSe (with the lattice parameters between those of bulk
      CdTe and CdSe). The ternary CdTe(x)Se(1-x) QDs were emitting in the red to near
      infrared (NIR) range. In order to enhance the PL properties and reduce the
      sensitivity to oxidation of CdTe-based QDs, the CdTe(x)Se(1-x) QDs were coated
      with Cd(y)Zn(1-y)S multishells by using different growth kinetics of CdS and ZnS.
      The coated QDs exhibited a controlled red shift of PL compared with the initial
      CdTe(x)Se(1-x) cores and revealed much improved PL intensity. Because of thier
      tunable emission from red to NIR, these composite QDs open new possibilities in
      band gap engineering and in developing NIR fluorescent probes for biological
      imaging and detection.

PMID- 24745261
TI  - Pd nanoparticles supported on MIL-101: an efficient recyclable catalyst in
      oxidation and hydrogenation reactions.
AB  - Pd nanoparticles supported on the chromium terephthalate metal organic framework
      MIL-101 (Pd/MIL-101) in different loadings (0.9 and 4.5 wt%) have been
      successfully prepared through a simple Pd-acetate adsorption and reduction in
      acetone, and tested as catalyst for selected liquid phase oxidation and
      hydrogenation reactions. The materials were characterized by XRD, N2 adsorption-
      desorption isotherm, TEM, SEM-EDX and ICP analysis. The parent MIL-101 structure
      was found well preserved after formation of Pd nanoparticles and after catalytic
      reaction runs. The present catalyst afforded good activity and selectivity for
      the oxidation of benzyl alcohol to benzaldehyde with 85% conversion and 97%
      selectivity using air (1 atm) at 85 degrees C after 14 h. The catalyst also
      showed good activity in the hydrogenation of the C=C bond in alkenes to
      corresponding alkanes and also benzaldehyde to benzyl alcohol at room temperature
      using H2 (1 atm). Rigorous test results confirmed that Pd-nanoparticles supported
      on MIL-101 are responsible for the catalytic reactions occurred. Pd/MIL-101 was
      reusable several times without losing the structural integrity and initial
      activity, and demonstrated significantly higher catalytic activities than those
      by a commercial Pd catalyst supported on activated carbon.

PMID- 24745262
TI  - Preparation and magnetic properties of multiferroic CuMnO2 nanoparticles.
AB  - CuMnO2 nanoparticles with diameters of 64 nm were synthesized by a novel wet
      chemical method. An optimized two-step annealing method was developed through the
      analysis of thermogravimetric differential thermal analysis (TG-DTA) measurements
      in order to obtain single-phase CuMnO2. A sharp exothermic peak was observed in
      the DTA curve at approximately 500 K where structural changes of the copper
      oxides and manganese oxides in the precursor are expected to occur. It is
      believed that Cu+ ions were oxidized to Cu2+ ions and that Mn2+ ions were
      oxidized to Mn3+ ions in the Cu-Mn-O system. Deoxidization reactions were also
      found at approximately 1200 K. The optimized annealing temperature for the first
      step was determined to be 623 K in air. The optimized annealing temperature for
      the second step was 1173 K in an Ar atmosphere. Magnetization measurements
      suggested an antiferromagnetic spin ordering at approximately 50 K. It was
      expected that Mn3+ spin interactions induced magnetic phase transition affected
      by definite temperature.

PMID- 24745263
TI  - Design of smart nanogels that respond to physiologically relevant pH values and
      temperatures.
AB  - Herein, we report the synthesis and characterization of monodisperse 'smart'
      nanogels that exhibit a sharp volume phase transition at physiologically relevant
      temperatures and pH values. The nanogels were prepared by precipitation
      copolymerization of N-isopropylacrylamide (NIPAAm) and propylacrylic acid (PAA).
      Briefly, the reaction was performed using a PAA feed of between 0 and 10 mol% in
      the presence of a crosslinker at 70 degrees C. The size of the nanogel particles
      was determined as a function of pH and temperature using dynamic light scattering
      (DLS). At room temperature, the NIPAAm-PAA nanogels were discrete, spherical
      structures with diameters ranging from 200 to 250 nm. The hydrodynamic diameter
      of the nanogels decreased to ca. 100-150 nm when the solution temperature was
      increased to 37 degrees C. At 37 degrees C, when the pKa was below that of the
      NIPAAm-PAA (ca. 6.0), the gels collapsed and aggregated. However, at 37 degrees C
      and a physiological pH of 7.4, the nanogels did not fully collapse due to the
      charge-charge repulsion derived from the ionized carboxyl groups of the PAA.
      Similar phase transition behavior was observed with the corresponding linear
      copolymers. Thus, such nanogel particles could be useful for releasing drugs in
      regions of local acidosis, including sites of infection, tumors, ischemia, and
      intracellular endosomes.

PMID- 24745264
TI  - Turbulent heat transfer and pressure drop characteristics of dilute water based
      Al2O3-Cu hybrid nanofluids.
AB  - A study on fully developed turbulent convective heat transfer and pressure drop
      characteristics of Al2O3-Cu/water hybrid nanofluid flowing through a uniformly
      heated circular tube is presented in this paper. For this, Al2O3-Cu nanocomposite
      powder was synthesized in a thermo chemical route using hydrogen reduction
      technique and dispersed the hybrid nano powder in deionised water to form a
      stable hybrid nanofluid of 0.1% volume concentration. The prepared powder was
      characterized by X-ray Diffraction (XRD) and Scanning Electron Microscope (SEM)
      to confirm the chemical composition, determine the particle size and study the
      surface morphology. Stability of the nanofluid was ensured by pH and zeta
      potential measurements. The average heat transfer enhancement for Al2O3-Cu/water
      hybrid nanofluid is 8.02% when compared to pure water. The experimental results
      also showed that 0.1% Al2O3-Cu/water hybrid nanofluids have slightly higher
      friction factor compared to 0.1% Al2O3/water nanofluid. The empirical
      correlations proposed for Nusselt number and friction factor were well agreed
      with the experimental data.

PMID- 24745265
TI  - Facile and rapid synthesis of pyrochlore W2O6 x H2O nanoplate via a fluorinion
      assisted hydrothermal process.
AB  - Pyrochlore W2O6 x H2O were successfully prepared via a facile and rapid
      hydrothermal process in the presence of fluorinion. It is worth noting that our
      developed method can efficiently overcome the tedious process in the preparation
      of nanostructured tungstic oxide in the previous reports. The as-prepared samples
      have been characterized by XRD, SEM and TEM. Results showed the morphologies of
      the samples were nanoplate and the thickness of the plate was estimated at about
      several nanometers. TEM image further revealed that the plates were trigonal-like
      with equal lengths of about 300 nm. Furthermore the selected area electron
      diffraction (SAED) pattern taken from a single nanoplate indicated that the
      nanoplates were the single crystals with a preferential growth direction along
      the [011] direction. The effect of the additive ions on the formation has also
      been discussed. It was found that the fluorinion played a key role in the
      formation of W2O6 x H2O nanoplates. It is hoped that our work could provide a new
      insight into the facile and rapid preparation of metal oxide nanomaterials.

PMID- 24745266
TI  - Optical and magnetic properties of Co-doped CuO flower/plates/particles-like
      nanostructures.
AB  - In this study, pure and Co-doped CuO nanostructures (0.5, 1.0, 1.5, and 2.0 at
      wt% of Co) were synthesized by microwave combustion method. The prepared samples
      were characterized by X-ray diffraction (XRD), high resolution scanning electron
      microscopy (HR-SEM), energy dispersive X-ray analysis (EDX), diffuse reflectance
      spectroscopy (DRS), photoluminescence (PL) spectroscopy and vibrating sample
      magnetometry (VSM). Powder X-ray diffraction patterns refined by the Rietveld
      method indicated the formation of single-phase monoclinic structure. The surface
      morphology and elemental analysis of Co-doped CuO nanostructures were studied by
      using HR-SEM and EDX. Interestingly, the morphology was found to change
      considerably from nanoflowers to nanoplates then to nanoparticles with the
      variation of Co concentration. The optical band gap calculated using DRS was
      found to be 2.1 eV for pure CuO and increases up to 3.4 eV with increasing cobalt
      content. Photoluminescence measurements also confirm these results. The magnetic
      measurements indicated that the obtained nanostructures were ferromagnetic at
      room temperature with an optimum value of saturation magnetization at 1.0 wt.% of
      Co-doped CuO, i.e., 970 micro emu/g.

PMID- 24745267
TI  - Optical properties and dye-sensitized solar cell applications of ZnO
      nanostructures prepared by microwave combustion synthesis.
AB  - In the present study, ZnO nanoparticles (ZNPs) and nanoflakes (ZNFs) were
      prepared by conventional combustion method and microwave combustion method,
      respectively. The structural phase and morphology were investigated by using X
      ray diffraction (XRD), high resolution scanning electron microscopy (HR-SEM) and
      high resolution transmission electron microscopy (HR-TEM). The crystallite size
      was calculated using Scherrer formula, and it lies in the range of 20-21 nm for
      ZNFs and 23-28 nm for ZNPs. The elemental analysis was investigated by energy
      dispersive X-ray analysis (EDX). Also, absorbance and emission spectra were
      measured by using diffuse reflectance (DRS) and photoluminescence (PL) studies.
      The band gap was measured using Kubelka-Munk model and it shows 3.47 eV for ZNFs
      and 3.26 eV for ZNPs. A fill factor (FF) of 0.57, short-circuit current (J(sc))
      of 8.02 mA/cm2, open-circuit voltage (V(oc)) of 0.70 V and an overall light to
      electricity conversion efficiency (eta) of 1.62% were obtained from the dye
      sensitized solar cell (DSSCs) based on ZNFs.

PMID- 24745268
TI  - Probing the protein conformation and adsorption behaviors in nanographene oxide
      protein complexes.
AB  - In this report, the adsorption characteristics and conformation changes of model
      protein bovine serum albumin (BSA) adsorbed on nanographene oxide (NGO) are
      described. The adsorption isotherms obtained at pH 4.0, 4.7, 7.4 and 8.8 show
      that NGO has the highest affinity for BSA in the acid environment of pH 4.0, but
      the protein adsorption capacity decreases with the pH value increasing. The data
      imply that the spontaneously binding of BSA to the NGO surfaces is mainly due to
      the protein conformation and an electrostatic attraction mechanism. The
      fluorescence and synchronous fluorescence spectroscopic studies show that NGO
      quenches the fluorescence of BSA both statically and dynamically, and induces
      obvious perturbations on the conformation of BSA as well as the microenvironments
      around the Trp and Tyr residues. Moreover, analysis of the secondary structure of
      the proteins via Fourier transform infrared spectroscopy revealed that evident
      secondary structural changes may undergo upon adsorption. This study gives an
      insight into the interaction between NGO and proteins, which is critical in the
      design of optimal graphene nanosheets-protein conjugates.

PMID- 24745269
TI  - DNA engineered tri-functional Ni-Au nano-chain: understanding of its formation
      and novel magnetic properties.
AB  - A plausible mechanism have been proposed here on the formation of chain like
      structure of Ni-Au-DNA (deoxyribo nucleic acid) composite which has been
      synthesized by simple wet-chemical process. The composite has been designed in
      such a fashion that it can be easily probed by optically, electrically and
      magnetically. In this paper, we are reporting its structural and physical
      properties in detail. Optical properties have been probed by Circular Dichroism
      (CD) which indicates no denaturization or melting of DNA even after formation of
      the composite structure. X-ray diffraction (XRD) study and Fourier transform
      infrared spectroscopy (FTIR) analysis show the nickel and gold are fcc in phase
      and bound to DNA through chemical bond, respectively. The composite shows room
      temperature semiconductor behavior. Temperature dependent magnetization and
      magnetic hysteresis loops are investigated in detail. The detail study of the
      composite indicates a possibility of its capability to be used in bio-devices.
      Furthermore, the tri-functionality of the composite will open-up its versatile
      applications.

PMID- 24745270
TI  - Immobilization of cytochrome c on the cylindrical mesoporous silica extrudates.
AB  - Siliceous and aluminum containing C12-MCM-41, C16-MCM-41 and SBA-15 mesoporous
      molecular sieves were synthesized in the powder (P) form by hydrothermal method.
      These materials were shaped into cylindrical extrudate (Ex) form by compounding
      with additives such as bentonite (binder), methyl cellulose and water. The
      adsorption of cytochrome c (cyt c) onto the extrudates of these mesoporous
      molecular sieves was studied at different solution pH. It was observed that
      maximum adsorption was found to be near the isoelectric point (pI) of the
      protein. The extrudates of SBA-15 showed a maximum amount of cyt c adsorption
      capacity and this may be due to the high pore volume and large pore diameter
      compared to other C12-MCM-41(Ex) and C16-MCM-41(Ex). Incorporation of aluminium
      in to the siliceous material showed maximum adsorption of cyt c compared to pure
      siliceous materials. The observed consequence may be due to the strong
      electrostatic interaction between the negative charges on the aluminium sites and
      positively charged amino acid residues of cyt c.

PMID- 24745271
TI  - Synthesis of carbon fibers with branched nanographene sheets for electrochemical
      double layer capacitor application.
AB  - We demonstrate a one step technique to synthesis the carbon fibers (CNFs) with
      branched nanographene sheets by the pulsed discharge (PD) plasma chemical vapor
      deposition (CVD) process. Highly crystalline branched nanographene sheets were
      directly grown from the surface of the carbon fibers to obtain a three
      dimensional (3D) nanostructure. The growth process can be explained from the
      catalyst support growth of the CNFs, and subsequently nucleation and growth of
      the nanographene sheets from the crystalline surface of the CNF. The deposited
      nanostructured films with different pulse discharge were used as an electrode for
      electrochemical double-layer capacitors (EDLC). It is observed that the
      capacitance is dependent on the morphology of the electrode materials and an
      optimum capacitance is obtained with the branched nanographene on CNFs.

PMID- 24745272
TI  - Visualizing preparation using asymmetrical choline-like ionic liquids for
      scanning electron microscope observation of non-conductive biological samples.
AB  - In this study, we investigated conductivity preparation for scanning electron
      microscope (SEM) observation that used novel asymmetrical choline-type room
      temperature ionic liquids (RTIL). By immersion in only an RTIL solution, clear
      SEM images of several types of biological samples were successfully observed. In
      addition, we could visualize protozoans using RTILs without any dilution. These
      results suggested that the asymmetrical choline-type RTILs used in this study are
      suitable for visualizing of biological samples by SEM. Treatment without the need
      for dilution can obviate the need for adjusting the RTIL concentration and
      provide for a rapid and easy conductivity treatment for insulating samples.

PMID- 24745273
TI  - Plasmon enhanced light trapping to improve efficiency of dye-sensitized solar
      cell.
AB  - Photoelectric conversion efficiency of a dye-sensitized solar cell was improved
      by trapping more light into the absorbing region using Ag nanoparticle. Improved
      light transmission is observed experimentally in silver nanoparticle coated FTO
      glass. The size of Ag nanoparticle is estimated as 110 nm by comparing
      theoretical results with experimental data. The transmission data is used to
      explore the effect on electrical parameters of dye-sensitized solar cell using
      theoretical model. Plasmon enhanced DSSC showed increased efficiency of 11.76%
      under AM1.5 solar spectrum compared with 10.86% for a DSSC without Ag
      nanoparticles.

PMID- 24745274
TI  - Full field analysis of critical dimension uniformity due to focal variation for
      contact features in extreme ultraviolet lithography.
AB  - Extreme ultraviolet (EUV) lithography is the leading candidate for 22 nm node
      technology and beyond. This research studies the influence of focal contributor
      on critical dimension (CD) variation in the EUV lithography and calculates the CD
      sensitivity to focal contributor based on the resist CD. EUV lithography
      parameters used in the simulation include NA = 0.25, 6 degrees oblique incident
      on the mask and source wavelength at 13.6 nm. The reflection design of EUV mask
      consists of 40 alternating Si/Mo layers, a ruthenium capping layer, and an
      absorber layer. The Rayleigh-Sommerfeld diffraction theory is adapted to solve
      the aerial image of contact hole (CH) feature layouts on the EUV mask. Then the
      resist CDs for the CH feature are measured at the position of the 10% from the
      bottom of resist profile. The target CD is 35 nm on wafer. The simulation results
      reveal the 2 nm discrepancy of spatial position for the aerial image curves
      measured between on the X metrology and Y metrology planes. The CDs of CH
      features with the iso-pitch are more sensitive to focal variation than the CDs of
      the features with the dense pitch. The maximum CD uniformity is 3.1 nm for the
      focal range at 90 nm.

PMID- 24745275
TI  - Template-assisted electrodeposition of iron nanostructures.
AB  - A facile approach to prepare iron nanostructures (nanowires, nanotubes, branched
      and multi-branched nanotubes) is reported by reduction of metal sulfide salts in
      the pores of an anodic aluminum membranes (AAMs) template with a back side Au
      sheet. The crystal structures and morphologies of Fe nanostructures are
      characterized by X-ray diffraction (XRD), field-emission scanning electron
      microscopy (SEM) and transmission electron microscope. The results indicate that
      the Fe nanostructures can replicate the inner architectures of the templates. The
      thickness of the Au film deposited on the back side of the AAMs and the inner
      structures of AAMs are the two key factors to determine the final morphologies of
      Fe nanostructures. This approach can be broadened to fabricate other metal
      nanostructures.

PMID- 24745276
TI  - Monolayer formation of luminescent germanium nanoparticles on silica surface in
      aqueous buffer solution.
AB  - The present paper reports monolayer formation of germanium nanoparticles (Ge NPs)
      on silica substrate. The NPs were prepared by hydride reduction of GeCl4, which
      is encapsulated with an inverse micelle of dimethyldioctylammonium bromide, with
      lithium aluminum hydride, and subsequent hydrogermylation of allylamine in the
      presence of platinum catalyst. The resultant NPs showed the blue
      photoluminescence property. Due to the terminal amine, the NPs were soluble
      highly in aqueous buffer solution. To fabricate a monolayer of Ge NPs, the
      chemical reactivity of the NPs was studied using a multi-functional microarray in
      which different kinds of siloxane monolayers were periodically aligned on a
      silica substrate. We observed using fluorescence microscope whether the terminal
      amines of the NPs recognize the specific monolayers in the microarray. In terms
      of fluorescence observation, the entire surface of the monolayer-covered
      microsize-domains emits uniformly the blue light. This suggests a high degree of
      coverage of the luminescent NPs covering over the monolayer regions in the
      microarray, and implies the non-occurrence of quenching through energy transfer
      between adjacent NPs.

PMID- 24745277
TI  - Dissipative particle dynamics simulation on paclitaxel loaded PEO-PPO-PEO block
      copolymer micelles.
AB  - Self-assembly behavior of the polymer drug loading micelle PEO-PPO-PEO was
      studied using dissipative particle dynamics (DPD) simulation method with various
      simulation steps. The distributions of drugs in polymer carriers were also
      investigated with different drug feed ratios. Polymer carriers distributed on the
      surface of the spherical micelle, and drugs were almost encapsulated in the inner
      of the micelle. Our simulation work demonstrates that the DPD simulation is
      effective to study the drug loaded systems and can give useful guidance on the
      design and preparation of new drug carriers with tailored properties.

PMID- 24745278
TI  - The effect of ligands on FePt-Fe3O4 core-shell magnetic nanoparticles.
AB  - FePt-Fe3O4 core-shell nanoparticles functionalized with 3,4-dihydroxyphenylacetic
      acid (DOPAC) and dimercaptosuccinic acid (DMSA) ligands were synthesized and
      characterized. We found that the DOPAC ligand enhances the magnetic properties of
      the FePt-Fe3O4 particles, in comparison with the DMSA ligand, which induces the
      oxidation of the shell layer that causes a significant reduction of the
      saturation magnetization. The synthesized magnetic nanoparticles were evaluated
      for applications in magnetic hyperthermia and magnetic resonance imaging contrast
      enhancement.

PMID- 24745279
TI  - Process-controlled multiscale morphologies in metal-containing block copolymer
      thin films.
AB  - Poly(styrene-block-ferrocenyldimethylsilane) (PS-b-PFS) is a metal-containing
      block copolymer that exhibits certain advantages as a scaffold for nanoporous
      membranes and as a mask for lithographic applications. These advantages include
      compatibility with a wide range of substrates, ease of control over domain
      morphologies and remarkable stability, which aid in the development of robust
      nanoporous networks or high-aspect-ratio patterns. An asymmetric cylinder-forming
      PS-b-PFS copolymer is subjected to different processing to manipulate the
      morphology of the phase-separated domains. Control of film structure and domain
      morphology is achieved by adjusting the film thickness, mode of annealing, and/or
      annealing time. Changing the process from thermal or solvent annealing to hybrid
      annealing (thermal and then solvent annealing in sequence) leads to the formation
      of mesoscale spherulitic and dendritic morphologies. In this communication, we
      show that reversing the order of the hybrid annealing (solvent annealing first
      and then thermal annealing) of relatively thick films (> 100 nm) on homogeneously
      thick substrates develops a discontinuous lamellar structure. Furthermore, the
      same processing applied on a substrate with a thin, mechanically flexible window
      in the center leads to the formation of sub-micron scale concentric ring
      patterns. Enhanced material mobility in the thick film during hybrid annealing
      along with dynamic rippling effects that may arise from the vibration of the thin
      window during spin casting are likely causes for these morphologies.

PMID- 24745280
TI  - Electronic transport through a benzene-shaped quantum dots system.
AB  - Based on the nonequilibrium Green function method, quantum transport through a
      benzene-shaped quantum dots system is studied. It is shown that the conductance
      spectrum is sensitive to the arrangement of energy levels of dots. When the
      energy levels of dots are mismatched, the conductance shows apparent asymmetric
      structure and striking novel conductance dips appear due to the interference
      between two distinct paths. The differential conductance as a function of
      magnetic flux always exhibits 2pi period. An overall suppression of differential
      conductance emerges for the condition that the levels of dots are all aligned and
      phi = (2n + 1)pi (n is an integer). In addition, the influence of temperature on
      the differential conductance is presented.

PMID- 24745281
TI  - Resistance of outmost shell- and embedded-end contacts of single- and multi
      bridged carbon nanotubes.
AB  - Single-bridged (SB) and multi-bridged (MB) carbon nanotubes (CNTs) were laterally
      grown between two electrodes capped on a thin nickel film, which functioned as
      catalysts. SB CNTs with outermost shell-end and embedded-end contacts on the
      electrodes showed varistor- or metal-like current-voltage (IV) characteristics.
      The devices were measured with fixed-amplitude AC superimposed on varying bias
      voltages. The MB CNTs contained both meal- and varistor-like CNTs, with the
      latter dominating the resistance at a higher bias. The results also imply that
      contact configuration significantly affects electrical interconnection.

PMID- 24745282
TI  - Color evolution and phase transformation behaviors of core-shell yellow iron(III)
      oxy-hydroxide pigments.
AB  - This manuscript reports on color evolution and phase transformation of alpha
      FeOOH and silica-coated alpha-FeOOH pigment. Goethite alpha-FeOOH, a yellow
      pigment, is the principle coloring agent in yellow, but it is not stable in the
      high temperature. To obtain stable and bright color of alpha-FeOOH, alpha-FeOOH
      nanorods were coated with silica. Core-shell pigments were calcined at high
      temperatures (300 and 1000 degrees C) and characterized by scanning electron
      microscopy (SEM), CIE L*a*b* color parameter measurements, transmission electron
      microscopy (TEM) and UV-vis spectroscopy. The yellow alpha-FeOOH was transformed
      to alpha-Fe2O3 with red, brown at 300, 1000 degrees C, respectively. In contrast,
      the silica-coated a-FeOOH retained a red coloration with high a* value at 300 and
      1000 degrees C.

PMID- 24745283
TI  - Preparation of alpha-Fe2O3 nanotubes by calcination of electrospun precursors.
AB  - The alpha-Fe2O3 nanotubes with diameters of 400-700 nm were prepared by
      calcination of electrospun precursors. The morphology of alpha-Fe2O3 nanotubes is
      mainly influenced by the water content in solution and heating rate during the
      calcination process. When the water content is about 17 wt.%, heating rate is 5
      degrees C/min and calcination temperature at 500 degrees C for 2 h, the optimized
      alpha-Fe2O3 nanotubes are obtained. These alpha-Fe2O3 nanotubes have a
      magnetization (M(s)) of 0.36 emu x (9-1) and coercivity (H(o)) of 1942 Oe and can
      be used in the nanospace technology.

PMID- 24745284
TI  - Spin-dependent quantum interference in Aharonov-Bohm ring embedded with two
      double-quantum-dot molecules.
AB  - The spin polarized transport properties through an Aharonov-Bohm ring embedded
      with a double quantum dot-molecule in each arm with Rashba spin-orbit (RSO)
      interaction is theoretically studied in the framework of the equation of motion
      of Green's function. Based on molecular state representation, the anti-resonance
      phenomenon in the conductance spectrum is readily explained. We found that the
      position of antiresonant peaks in conductance spectrum is determined by the
      interdot coupling strengths. Moreover, the magnitude of conductance of each spin
      component can be manipulated by the Rashba spin orbit interaction strength.
      Especially only one spin component electron can be allowed to transport through
      this structure by modulating the strength of RSO interaction properly.

PMID- 24745285
TI  - Thermogravimetric analysis of atomized ferromagnetic composites with multiwalled
      carbon nanotubes: an unusual behavior of nickel in nanospace.
AB  - A spin polarization of atomized ferromagnetic atoms like cobalt or nickel in nano
      space results in the modification of the electron configuration in the
      ferromagnetic atom that changes its oxidative property. We have prepared cobalt
      and nickel composites with multiwalled carbon nanotubes using atomized cobalt and
      nickel particles, for investigating their thermal oxidative behavior by
      thermogravimetric analysis (TGA). The composites showed the absence of a thermal
      oxidation in the temperature range of ambient to the break down temperature of
      multiwalled carbon nanotubes at 800 degrees C. At this temperature while Co
      composite forms cobalt oxide, the Ni composite becomes volatile that results in
      the divergent behavior of the two ferromagnetic compounds with a weight gain
      observed in TGA for Co and a loss for Ni. The mechanisms operating in the two
      cases are discussed in this work.

PMID- 24745287
TI  - High-resolution transmission electron microscopy of isolated fullerene C60
      molecules.
AB  - Isolated fullerene C60 molecules on the surfaces of C60 crystals were observed by
      high-resolution transmission electron microscopy. The observed images were
      compared with the simulated images. It was found that the orientation of the
      observed C60 molecules can be identified.

PMID- 24745286
TI  - Carbon nanofiber interconnect RF characteristics improvement with deposited
      tungsten contacts.
AB  - Carbon nanotubes (CNTs) and carbon nanofibers (CNFs) are potential materials for
      high-performance electronic devices and circuits due to their light weight and
      excellent electrical properties such as high current capacity and tolerance to
      electromigration. In addition, at high frequencies, these materials exhibit
      transport behavior which holds special promise for applications as on-chip
      interconnects. Contact resistance at CNF-metal interface is a major factor in
      limiting the electrical performance of CNF interconnects at all frequencies. In
      this paper, it is demonstrated that the contact resistance can be minimized and
      the high-frequency characteristics much enhanced by depositing tungsten on CNF
      metal electrode contacts.

PMID- 24745288
TI  - Oral and maxillofacial pathology case of the month. Herniated dental follicle.

PMID- 24745289
TI  - CAT of the month. Electrical pulp testing has not been shown to be superior to
      cold test in diagnosing pulp vitality (UT CAT #2533).

PMID- 24745290
TI  - Is the fast lane the tortoise or the hare?

PMID- 24745291
TI  - Prepared for the challenge.

PMID- 24745292
TI  - My life as a correctional facility dentist.

PMID- 24745293
TI  - Sharing a roof.

PMID- 24745294
TI  - A practice with one big voice.

PMID- 24745295
TI  - The advantages of a military practice.

PMID- 24745296
TI  - Being a rural dentist.

PMID- 24745298
TI  - My positive experience.

PMID- 24745297
TI  - Pediatric public health.

PMID- 24745299
TI  - Transitioning for the future.

PMID- 24745300
TI  - Enlightened diagnosis by transillumination.

PMID- 24745301
TI  - Implant solutions for the implant patient: diagnosis and treatment planning for
      predictable results.

PMID- 24745302
TI  - 9 tips for making your slow season more profitable.

PMID- 24745303
TI  - Formation of conductive networks with both segregated and double-percolated
      characteristic in conductive polymer composites with balanced properties.
AB  - Morphological control of conductive networks involves the construction of
      segregated or double-percolated conductive networks is often reported to reduce
      the electrical percolation threshold of conductive polymer composites (CPCs) for
      better balance among electrical conductivity, mechanical properties, and filler
      content. Herein, the construction of conductive networks with both segregated and
      double-percolated characteristics is achieved based on polypropylene
      (PP)/polyethylene (PE) and multi-wall carbon nanotubes (CNTs). CNTs were firstly
      dispersed in PE; then PE/CNTs were compounded with PP particles well below the
      melting temperature of PP. It is observed that the percolation threshold (pc)
      decreases with increasing PP particle size (size 3.6 mm, pc=0.08 wt %), which
      agrees with previous theoretical prediction and experiment in much smaller
      particle size range. To further study this, the amount of CNTs in PE is varied.
      It is shown that the degree of PE/CNTs coating on PP particles varies with CNTs
      as well as PE content in these composites, and have significant influence on the
      final electrical property. Furthermore, a model combines classical percolation
      theory and model for segregated network has been proposed to analyze the effect
      of particle size, degree of coating and thickness of coating on the percolation
      behavior of these CPCs. In such a model the percolation of CNTs in PE phase as
      well as PENT phase in the segregated structure can be described. Overall, through
      such method, a much better balance among mechanical property, conductivity, and
      filler content is achieved in these CPCs comparing with the results in
      literature.

PMID- 24745304
TI  - A four-step total synthesis of radermachol.
AB  - Radermachol has been synthesized in four steps and an overall yield of 22% via
      key ytterbium triflate catalyzed furannulation and intramolecular nucleophilic
      acylation reactions. 

PMID- 24745305
TI  - Rate constants and kinetic isotope effects for methoxy radical reacting with NO2
      and O2.
AB  - Relative rate studies were carried out to determine the temperature dependent
      rate constant ratio k1/k2a: CH3O. + O2 -> HCHO + HO2. and CH3O. + NO2 (+M) ->
      CH3ONO2 (+M) over the temperature range 250-333 K in an environmental chamber at
      700 Torr using Fourier transform infrared detection. Absolute rate constants k2
      were determined using laser flash photolysis/laser-induced fluorescence under the
      same conditions. The analogous experiments were carried out for the reactions of
      the perdeuterated methoxy radical (CD3O.). Absolute rate constants k2 were in
      excellent agreement with the recommendations of the JPL Data Evaluation panel.
      The combined data (i.e., k1/k2 and k2) allow the determination of k1 as 1.3(
      0.5)(+0.9) * 10(-14) exp[-(663 +/- 144)/T] cm(3) s(-1), corresponding to 1.4 *
      10(-15) cm(3) s(-1) at 298 K. The rate constant at 298 K is in excellent
      agreement with previous work, but the observed temperature dependence is less
      than was previously reported. The deuterium isotope effect, kH/kD, can be
      expressed in the Arrhenius form as k1/k3 = (1.7(-0.4)(+0.5)) exp((306 +/- 70)/T).
      The deuterium isotope effect does not appear to be greatly influenced by
      tunneling, which is consistent with a previous theoretical work by Hu and Dibble.
      (Hu, H.; Dibble, T. S., J. Phys. Chem. A 2013, 117, 14230-14242.)

PMID- 24745307
TI  - Effect of surfactant addition on removal of microbubbles using ultrasound.
AB  - It is difficult to control the bubble in a liquid by the external operation,
      because the behavior of the bubble is controlled in buoyancy and flow of liquid.
      On the other hand, microbubbles, whose diameter is several decades MUm, stably
      disperse in static liquid because of their small buoyancy and electrical
      repulsion. When an ultrasound, whose frequency was 2.4 MHz, was irradiated, the
      milky white microbubbles suspended solution became rapidly clear. In this study,
      the effects of surfactant addition on the removal of microbubbles from a liquid
      in an ultrasonic field were investigated. The efficiency of removal of
      microbubbles decreased with surfactant addition. Surfactant type influenced the
      size of agglomerated microbubbles, and the efficiency of removal of microbubbles
      changed. The surface of microbubble was modified by surfactant adsorption, and
      the steric inhibition influenced the removal of microbubbles.

PMID- 24745306
TI  - Consumption of Cisatracurium in different age groups, using a closed loop
      computer controlled system.
AB  - BACKGROUND: We devised this study to quantify the effect of age on the
      consumption of cisatracurium under general anaesthesia, using a computer
      controlled closed loop infusion system. We further investigated this effect on,
      sufentanil and propofol consumption. METHODS: 74 patients of physical status I
      and II, requiring general anaesthesia for elective abdominal surgery, were
      assigned to three groups. Patients in group 1 were aged from 20 to 45, group 2
      were from 46 to 64, and group 3 above 65 years old. General Anesthesia was
      maintained with propofol and muscle paralysis was maintained using a closed-loop
      computer controlled infusion of cisatracurium. For analgesia, intermittent bolus
      of sufentanil 10 MUg was given. RESULTS: Cisatracurium consumption in group 1, 2
      and 3 were 1.8 +/- 0.3, 1.6 +/- 0.4 and 1.3 +/- 0.4 MUg/kg/min respectively.
      There was significant difference of cisatracurium consumption between group 1 and
      3 (P = 0.002), and the consumption of cisatracurium in group 3 was less as
      compared with group 2 (P = 0.04). The average recovery index of patients in group
      1, 2 and 3 were 8.8 +/- 2.6, 11.5 +/- 2.9 and 12.7 +/- 2.5 minutes respectively.
      There were difference between group 1 and 2 (P = 0.02). As compared with group 1,
      the recovery index was still longer in group 3 (P = 0.001). Patients in group 1,
      2 and 3 consumed an average sufentanil 0.4 +/- 0.1, 0.4 +/- 0.1 and 0.3 +/- 0.1
      MUg/kg/hr, respectively. There were statistical significant between group 1 and 3
      (P < 0.0001), and the same trend was found between group 2 and 3 (P = 0.03). The
      Consumption of propofol in group 1, 2 and 3 were 5.1 +/- 0.4, 4.3 +/- 0.6 and 3.1
      +/- 0.5 mg/kg/hr. The difference in the propofol consumption was found
      statistically significant when comparing between any two groups. CONCLUSION: We
      concluded that the sensitivity of anesthetic agents increased with age. Less
      medication was required to achieve a desirable effect in older patients specially
      those above 65 years of age, and the drug effect was prolonged. TRIAL
      REGISTRATION: ClinicalTrials.gov Identifier: NCT01785446.

PMID- 24745308
TI  - Patient-reported outcomes after neoadjuvant therapy for rectal cancer: a
      systematic review.
AB  - Neoadjuvant therapy followed by total mesorectal excision is standard of care for
      locally advanced rectal cancer. However, this approach has been previously shown
      to be associated with high rate of morbidity and it may have a negative effect on
      patients' reported outcomes (PROs). In order to summarize findings on the effect
      of the neoadjuvant approach on PROs, we systematically reviewed articles
      published in the last five years. Thirty-five articles met the inclusion
      criteria. Ten articles compared the effect of surgery with and without
      neoadjuvant therapy, six articles compared different neoadjuvant therapies, ten
      articles reported on patients who were all treated with neoadjuvant therapy, and
      nine articles examined the effect of neoadjuvant therapy in the analyses. The
      results are summarized by function investigated and critically commented. 

PMID- 24745309
TI  - Prognosis in epilepsy: initiating long-term drug therapy.
AB  - INTRODUCTION: Prognosis in epilepsy refers to the probability of either achieving
      seizure remission (SR), whether spontaneously or using antiepileptic drugs (AED),
      or failing to achieve control of epileptic seizures (ES) despite appropriate
      treatment. Use of AED is recommended after a second unprovoked ES. For a first
      episode, the decision of whether or not to start drug treatment depends on the
      risk of recurrence and the advantages or disadvantages of the antiepileptic drug.
      The main goal of treatment is achieving absence of ES without adverse effects
      (AE). AED is selected according to epilepsy type and the demographic and clinical
      characteristics of the patient. DEVELOPMENT: A PubMed search located articles and
      recommendations by the most relevant scientific societies and clinical practice
      guidelines concerning epilepsy prognosis and treatment. Evidence and
      recommendations are classified according to the prognostic criteria of the Oxford
      Centre for Evidence-Based Medicine (2001) and the European Federation of
      Neurological Societies (2004) for therapeutic actions. CONCLUSIONS: Most newly
      diagnosed epileptic patients achieve good control over their ES. The majority of
      the AEDs available at present provide effective control over all types of ES, and
      choice therefore depends on the patient's individual characteristics. Treatment
      should be initiated as monotherapy at the lowest effective dose, which in half of
      all patients provides ES control and is well tolerated. In cases in which the
      first AED is not effective, alternative therapy should be started, and
      monotherapy should be employed before combination therapy where possible. The
      probability of achieving good control over ES decreases with each successive
      treatment failure.

PMID- 24745310
TI  - Venous thromboembolism after elective shoulder surgery: a prospective cohort
      study of 175 patients.
AB  - BACKGROUND: The purpose of this study was to investigate the incidence of venous
      thromboembolism (VTE) after elective arthroscopic shoulder surgery. MATERIALS AND
      METHODS: One hundred seventy-five consecutive patients who underwent arthroscopic
      shoulder surgery were enrolled (mean age, 61 years). Patients who had VTE
      preoperatively and underwent trauma surgery or arthroplasty were excluded. All
      the patients used foot pumps or elastic stockings after surgery for deep venous
      thrombosis (DVT) prophylaxis. DVT in the 4 limbs was assessed by ultrasound
      before and after surgery. Pulmonary embolism was diagnosed by computed tomography
      pulmonary angiography. Risk factors related to DVT were assessed. RESULTS: The
      overall incidence of DVT was 10 of 175 patients (5.7%). Most of the DVT cases
      were detected at 1 to 2 days after surgery. All patients were asymptomatic. There
      were no patients who had symptomatic pulmonary embolism. However, an asymptomatic
      pulmonary embolus developed in 1 patient during the 3-month follow-up period.
      There were no significant differences between the DVT and non-DVT groups
      regarding the risk factors. DISCUSSION AND CONCLUSION: Our data have shown that
      symptomatic VTE is rare after elective arthroscopic shoulder surgery. However,
      asymptomatic VTE may occur even with DVT preventive measures. Because most of the
      DVTs were found in the calf veins, we recommend that surgeons pay attention to
      the possibility of DVT in the lower extremities even after arthroscopic shoulder
      surgery. The incidence of asymptomatic VTE after elective arthroscopic shoulder
      surgery was 5.7%. All patients were asymptomatic, and most of the DVTs occurred 1
      or 2 days after surgery.

PMID- 24745311
TI  - Surface-holding repair: an original arthroscopic rotator cuff repair technique.
AB  - BACKGROUND: Arthroscopic rotator cuff repair provides satisfactory results;
      however, there is still a high rate of re-tear. The objective of this study was
      to present a surface-holding technique that we recently developed for
      arthroscopic rotator cuff repair in detail and to evaluate the clinical outcome
      as well as cuff repair integrity with this new method. MATERIALS AND METHODS: A
      consecutive series of 116 patients with full-thickness rotator cuff tears
      underwent arthroscopic surface-holding repair and were monitored with the
      Japanese Orthopaedic Association, Constant-Murley, and University of California
      Los Angeles scores to assess the clinical outcome. The mean follow-up period was
      17.9 months (range, 12-40 months). Cuff repair integrity was evaluated by
      magnetic resonance imaging. RESULTS: All 3 rating systems at the time of final
      follow-up reflected a significant improvement in functional recovery of the
      shoulder compared with the preoperative scores. The overall rate of rotator cuff
      retear was 19.0% (22 of 116 shoulders), and the rates were 13.6% (9 of 66
      shoulders) for small and medium-sized tears and 26% (13 of 50 shoulders) for
      large and massive tears. The rate for large and massive tears was much higher in
      patients older than 70 years (58.3%) compared with those younger than 70 years
      (36.3%), whereas the retear rates were similar in these 2 groups (22.2% and
      17.5%, respectively). CONCLUSIONS: Arthroscopic surface-holding repair technique
      with medial suture and transosseous fixation improved rotator cuff healing. This
      method may be useful both for young patients and for elderly patients, who
      frequently have chronic large and massive tears, including osteoporotic bones.

PMID- 24745312
TI  - Contribution of oxidative stress to the degeneration of rotator cuff entheses.
AB  - BACKGROUND: Rotator cuff degeneration is one of the multiple factors that lead to
      rotator cuff tears; however, the precise mechanism of such degeneration still
      remains unclear. In this study, we investigated the supraspinatus tendon enthesis
      to clarify the link between rotator cuff degeneration and oxidative stress in
      antioxidant enzyme superoxide dismutase 1 (Sod1)-deficient mice (Sod1(-/-)).
      METHODS: The supraspinatus tendon and humeral head were isolated and fixed to
      prepare histologic sections from wild-type and Sod1(-/-) male mice at 20 weeks of
      age. Hematoxylin-eosin staining was performed to assess the histomorphologic
      structure. To investigate the collagen fibers, we examined spatially aligned
      collagen fibers using a polarizing microscope and assessed the amount of collagen
      using immunohistochemical staining. To analyze the tissue elasticity, we measured
      the tissue acoustic properties using scanning acoustic microscopy. RESULTS: The
      Sod1(-/-) mice showed histologic changes, such as a misaligned 4-layered
      structure and fragmented tidemark, in the enthesis. Sod1 loss also decreased the
      amount of brightly diffracted light and type I collagen, indicating collagen
      downregulation. The scanning acoustic microscopy analysis showed that the speed
      and attenuation of sound were increased in the nonmineralized fibrocartilage of
      the Sod1(-/-) mice, suggesting decreased mechanical properties in the
      supraspinatus enthesis. CONCLUSION: Sod1 deficiency-induced degeneration is
      associated with impaired elasticity in the supraspinatus tendon enthesis,
      recapitulating human rotator cuff degeneration. These results suggest that
      intracellular oxidative stress contributes to the degeneration of rotator cuff
      entheses.

PMID- 24745313
TI  - Quantitative evaluation of fatty degeneration of the supraspinatus and
      infraspinatus muscles using T2 mapping.
AB  - BACKGROUND: Although fatty degeneration of the rotator cuff muscles has been
      reported to affect the outcomes of rotator cuff repairs, only a few studies have
      attempted to quantitatively evaluate this degeneration. T2 mapping is a
      quantitative magnetic resonance imaging technique that potentially evaluates the
      concentration of fat in muscles. The purpose of this study was to investigate
      fatty degeneration of the rotator cuff muscles by using T2 mapping, as well as to
      evaluate the reliability of T2 measurement. METHODS: We obtained magnetic
      resonance images including T2 mapping from 184 shoulders (180 patients; 110 male
      patients [112 shoulders] and 70 female patients [72 shoulders]; mean age, 62
      years [range, 16-84 years]). Eighty-three shoulders had no rotator cuff tear
      (group A), whereas 101 shoulders had tears, of which 62 were incomplete to medium
      (group B) and 39 were large to massive (group C). T2 values of the supraspinatus
      and infraspinatus muscles were measured and compared among groups. Intraobserver
      and interobserver variabilities also were examined. RESULTS: The mean T2 values
      of the supraspinatus in groups A, B, and C were 36.3 +/- 4.7 milliseconds, 44.2
      +/- 11.3 milliseconds, and 57.0 +/- 18.8 milliseconds, respectively. The mean T2
      values of the infraspinatus in groups A, B, and C were 36.1 +/- 5.1 milliseconds,
      40.0 +/- 11.1 milliseconds, and 51.9 +/- 18.2 milliseconds, respectively. The T2
      value significantly increased with the extent of the tear in both muscles. Both
      intraobserver and interobserver variabilities were more than 0.99. CONCLUSION: T2
      mapping can be a reliable tool to quantify fatty degeneration of the rotator cuff
      muscles.

PMID- 24745314
TI  - Reliability of the classification and treatment of dislocations of the
      acromioclavicular joint.
AB  - BACKGROUND: We evaluated interobserver and intraobserver reliability of the
      classification and treatment of acromioclavicular (AC) joint dislocations and
      assessed the impact of adding 3-dimensional computed tomography (3D CT) on the
      reliability of classification and treatment choice. METHODS: Ten surgeons
      independently reviewed plain radiographs and 3D CT in 28 cases with AC joint
      dislocation. Images from each case were randomly presented to the observers, with
      plain radiographs alone being presented first, followed by plain radiographs plus
      3D CT 2 weeks later. Four weeks later, they repeated the same survey to evaluate
      intraobserver reliability. Reliability was assessed on the basis of Fleiss kappa
      values. RESULTS: On the basis of plain radiographs alone, interobserver and
      intraobserver reliability of the Rockwood classification were fair (kappa = .214)
      and moderate (kappa = .474), respectively. Interobserver and intraobserver
      reliability of treatment were both fair (kappa = .213 and .399, respectively). On
      the basis of a combination of plain radiographs and 3D CT, interobserver and
      intraobserver reliability of the Rockwood classification were slight (kappa =
      .177) and moderate (kappa = .565), respectively. Interobserver and intraobserver
      reliability of treatment were fair (kappa = .253) and moderate (kappa = .554),
      respectively. There were no significant differences in reliability between the
      two groups in terms of any kappa values. CONCLUSION: This study suggests an
      overall lack of reliability of the Rockwood classification of AC joint
      dislocations and of decisions regarding their treatment. There is especially poor
      agreement between experienced shoulder surgeons. The addition of 3D CT did not
      improve reliability of classification and treatment of AC joint dislocations.

PMID- 24745315
TI  - Diabetes as a risk factor for poorer early postoperative outcomes after shoulder
      arthroplasty.
AB  - BACKGROUND: Although diabetes has been associated with increased perioperative
      morbidity and mortality after hip and knee arthroplasty, its impact on early
      postoperative outcomes after shoulder replacement remains relatively unexplored.
      The purpose of the study was to determine the association of diabetes with in
      hospital death, complications, length of stay, non-homebound disposition, and
      cost in patients undergoing shoulder arthroplasty. METHODS: By use of the
      Nationwide Inpatient Sample database for the year 2011, an estimated 66,485
      patients having undergone shoulder arthroplasty were identified and separated
      into groups with (21%) and without (79%) diabetes mellitus. Comparisons of
      specific outcome measures between diabetic and nondiabetic cohorts were performed
      by bivariate and multivariable analyses with logistic regression modeling.
      RESULTS: Diabetes mellitus was independently associated with in-hospital death, a
      number of perioperative complications, prolonged hospital stay, and increased non
      homebound disposition after shoulder arthroplasty. The presence of diabetes was
      not associated with increased hospital cost. CONCLUSION: Patients with
      preexisting diabetes are at higher risk for perioperative morbidity and mortality
      after shoulder arthroplasty. Future prospective research should explore in more
      detail the relationship between diabetes and shoulder arthroplasty outcomes.

PMID- 24745316
TI  - Primary repair of retracted distal biceps tendon ruptures in extreme flexion.
AB  - BACKGROUND: Distal biceps tendon ruptures may have tendinous retraction, making
      primary repair difficult and calling into question the need for graft
      reconstruction. The decision for when to primarily fix or augment high-flexion
      repairs has not been addressed. We hypothesized high-flexion repairs would have
      good outcomes without graft augmentation. The purpose of this study was to
      examine allograft use and outcomes of distal biceps tendon ruptures requiring
      repair in greater than 60 degrees  of flexion. METHODS: This was a retrospective
      case-control study 188 distal biceps tendon repairs; of these, 19 chronic and 4
      acute cases were identified with repairs of >60 degrees  of flexion using a 2
      incision technique. Graft need, complications, and Mayo Elbow Performance Score
      to assess function, were examined with a record review. Patients were surveyed
      regarding return to work and subjective satisfaction. A control group matched for
      surgeon, chronicity, and age, but without a high-flexion repair, was compared
      with cases by using the Student paired t test. RESULTS: Graft augmentation was
      used in 1 patient with poor tendon quality. The Mayo Elbow Performance Score was
      100 for all 23 patients, with extension/flexion range of motion from 3 degrees 
      to 138 degrees . All were subjectively "very satisfied/satisfied," with full work
      return, yet 3 reported mild fatigability. There were 4 complications: 3 transient
      lateral antebrachial cutaneous neurapraxias and 1 rerupture at the myotendinous
      junction after retrauma. Differences between cases and controls were not
      statistically significant. CONCLUSION: Contracted distal biceps tendons may be
      reliably reattached to their anatomic insertion with up to 90 degrees  of elbow
      flexion. This lessens the need for reconstruction in such circumstances.

PMID- 24745317
TI  - Intrawound application of vancomycin reduces wound infection after open release
      of post-traumatic stiff elbows: a retrospective comparative study.
AB  - BACKGROUND: With the improvements in wound healing through the use of intravenous
      prophylactic antibiotics and technical refinements, postoperative elbow
      infections have become less common but still occur in certain elective elbow
      surgeries. The objective of this study was to evaluate the safety and efficacy of
      prophylactic application of vancomycin into the operative site to reduce the
      incidence of infection after the open release of post-traumatic stiff elbows.
      METHODS: A retrospective review of 272 such patients during a 4-year period was
      performed. In the control group (93 patients), simple prophylaxis with standard
      intravenous antibiotics was performed; in the vancomycin group (179 patients),
      vancomycin powder was applied directly into the wound before closure along with
      standard intravenous prophylaxis. RESULTS: After a follow-up of at least 6
      months, the control group was found to have 6 infections (6.45%; confidence
      interval: 2.40%-13.52%) compared with none (0%; confidence interval: 0-2%.04%) in
      the vancomycin group, which was a statistically significant difference (P =
      .0027). No adverse effects were documented from the direct use of the vancomycin
      powder. CONCLUSIONS: The local application of vancomycin powder may be a
      promising means of preventing postoperative elbow infections after elbow release
      in patients with post-traumatic elbow stiffness.

PMID- 24745318
TI  - Elbow joint position sense after total elbow arthroplasty.
AB  - BACKGROUND: Multiple human experiments have shown that articular lesions can have
      a negative effect on proprioception. The influence of total elbow arthroplasty on
      joint position sense has not been reported so far. The purpose of the study was
      to evaluate proprioception, defined as a joint position sense, after total elbow
      arthroplasty. METHODS: The study included 16 patients with unilateral
      semiconstrained linked total elbow arthroplasty and 21 healthy volunteers. The
      evaluation included measurement of active and passive reproduction of joint
      position sense of both elbows after surgery and the control groups. Reference
      angles included extension to 50 degrees  and 70 degrees  and flexion to 110
      degrees . We also assessed function of the elbow in arthroplasty group using the
      Mayo Elbow Performance Score, the Disability of the Arm, Shoulder and Hand score,
      and a visual analog scale for pain level. RESULTS: The average value of error of
      passive reproduction of joint position for elbows after arthroplasty was
      significantly inferior for all evaluated positions compared with the
      contralateral elbow and with the control group, respectively, at 110 degrees 
      flexion: 4.3 degrees , 2.7 degrees , and 3.2 degrees ; at 70 degrees  extension:
      4.9 degrees , 2.9 degrees , and 2.7 degrees ; and at 50 degrees  extension: 6.3
      degrees , 3.8 degrees , and 3.8 degrees . The average value of error of active
      reproduction of joint position for the arthroplasty group was also significantly
      inferior, respectively, at 110 degrees  flexion: 3.5 degrees , 1.9 degrees  and 2
      degrees ; and at 50 degrees  extension: 4.4 degrees , 3.3 degrees , and 3 degrees
      . CONCLUSION: Proprioception in elbows that undergo total arthroplasty is
      significantly inferior compared with the contralateral site of the patient and in
      the healthy control group.

PMID- 24745319
TI  - Results of parallel plate fixation of comminuted intra-articular distal humeral
      fractures.
AB  - BACKGROUND: This study investigated the results of parallel plate fixation of
      comminuted distal humeral fractures in a consecutive series of patients. METHODS:
      Parallel plate fixation was used in 47 patients (30 women), mean age 60 years
      (range 18-98 years), with Arbeitsgemeinschaft fur Osteosynthesefragen (AO) type C
      distal humeral fractures during 2007 to 2011. Medical records and radiographs
      were retrospectively assessed. Thirty-five patients completed Disabilities of
      Arm, Shoulder and Hand (DASH) outcome measure and the RAND Medical Outcomes Study
      36-Item Short Form (SF-36) Health Survey. Twenty-seven patients underwent
      clinical examination, Mayo Elbow Performance Score (MEPS) rating, and radiography
      after 3.9 years (range, 1.6-7.9 years) of follow-up. RESULTS: The mean flexion
      arc was lower on the affected side vs the unaffected elbow (123 degrees  vs 140
      degrees , P = .03). The mean MEPS was 88; the result was excellent in 14, good in
      8, fair in 3, and poor in 2 patients. DASH results indicated slight impairment of
      upper extremity function compared with the reference value (26 vs 10, P = .001).
      RAND SF-36 scores indicated normal quality of life compared with reference values
      from the Finnish population. Forty-four fractures united uneventfully. One case
      each of nonunion and malunion occurred. One olecranon osteotomy failed to unite.
      There were 3 cases of infection. Prominent hardware was a common late problem,
      and plates often required removal. The complication rate was 7 of 47 (15%); 4 of
      these patients (9%) required reoperation. The hardware removal rate was 13 of 47
      (28%). CONCLUSION: Parallel plate fixation is an effective method to treat
      comminuted distal humeral fractures. Good elbow function can be restored in most
      cases with minor impairments that do not worsen quality of life.

PMID- 24745320
TI  - A prospective multicenter clinical study of the Discovery elbow.
AB  - BACKGROUND: Semiconstrained total elbow arthroplasty is used to improve elbow
      function and reduce pain. Although effective, high complication rates exist, with
      the polyethylene bushing especially susceptible to failure. The Discovery Elbow
      System (Biomet Inc, Warsaw, IN, USA) contains a spherical bearing designed to
      minimize polyethylene wear. This prospective, multicenter clinical study
      investigated the 4-year (mean) outcomes of this elbow. METHODS: From 2002 to
      2009, 92 patients (71 women, 21 men; mean age, 63.9 years; range, 33.4-88.7
      years) received 99 Discovery elbows at 4 centers. The study cohort was limited to
      46 elbows with complete preoperative and minimum 2-year clinical (modified
      American Shoulder and Elbow Surgeons elbow score) and radiographic follow-up.
      RESULTS: Mean follow-up was 4.1 years (range, 2-5.9 years). All American Shoulder
      and Elbow Surgeons elbow score components improved significantly (P < .001). Mean
      flexion-extension arcs increased from 81 degrees  to 121 degrees  and pronation
      supination arcs from 134 degrees  to 163 degrees  (P < .001). Loose locking
      screws in 2 elbows (first-generation screws), a loose polyethylene bearing in 1
      (history of falls), and a condyle/bearing in 1 (deep infection) were exchanged.
      Among the 46 elbows, gross survivorship was humeral/ulnar components, 100%;
      condyles, 97.8%; bearings, 95.7%; and screws, 95.7%. One humeral component (2.2%)
      was radiographically loose but not revised. An additional elbow (elbow 47) that
      did not meet the criteria for inclusion (<2 years of follow-up) was revised due
      to a loose humeral component and was reported separately. CONCLUSION: The
      Discovery elbow increased function and decreased pain with high survivorship at a
      mean of 4.1 years.

PMID- 24745321
TI  - Amniotic coenzyme Q10: is it related to pregnancy outcomes?
AB  - Coenzyme Q10 (CoQ10 or ubiquinone) is an essential component of the mitochondrial
      electron transport chain and is also present in various cellular membranes and in
      plasma lipoproteins. Diabetes, cardiovascular, neurodegenerative, and
      preeclampsia diseases are all associated with an alteration of CoQ10 level or its
      redox status. During pregnancy, we note that the plasma content of CoQ10 is
      significantly higher than amniotic. In the fetal growth restriction group,
      amniotic total CoQ10 levels were significantly higher versus healthy, while the
      amniotic oxygen radical absorbing capacity level was significantly lower. A
      significant negative correlation was observed between amniotic total CoQ10 and
      birthweight. Our observation leads to the hypothesis that the amniotic
      midtrimester CoQ10 content may be a marker of subsequent obstetric complications.

PMID- 24745322
TI  - Structure and gene cluster of the O-antigen of Escherichia coli O30.
AB  - The acidic O-polysaccharide (O-antigen) of Escherichia coli O30 was isolated from
      the lipopolysaccharide and studied by sugar analysis and NMR spectroscopy. The
      following structure of the branched tetrasaccharide repeating unit was
      established, which is unique among known structures of bacterial polysaccharides:
      beta-D-GlcpNAc--1->2--->4)-beta-D-GlcpA-(1->4)-beta-D-GlcpA-(1->3)-alpha-D
      GlcpNAc-(1-> The O-antigen gene cluster of E. coli O30 was sequenced. The gene
      functions were tentatively assigned by comparison with sequences in the available
      databases and found to be in full agreement with the O-polysaccharide structure.

PMID- 24745323
TI  - How predictive are photosensitive epilepsy models as proof of principle trials
      for epilepsy?
AB  - PURPOSE: Human photosensitive epilepsy models have been used as proof of
      principle (POP) trials for epilepsy. Photosensitive patients are exposed to
      intermittent photic stimulation and the reduction in sensitivity to the number of
      standard visual stimulation frequencies is used as an endpoint. The aim of this
      research was to quantify the predictive capabilities of photosensitive POP
      trials, through a survey of current literature. METHODS: A literature search was
      undertaken to identify articles describing photosensitive POP trials. Minimally
      efficacious doses (MEDs) in epilepsy were compared to doses in the POP trials
      that produced 50-100% response (ED50-100). Ratios of these doses were calculated
      and summarised statistically. RESULTS: The search identified ten articles
      describing a total of 17 anti-epileptic drugs. Of these, data for both MED and
      ED50-100 were available for 13 anti-epileptic drugs. The average ratio of MED to
      ED50-100 was 0.95 (95% CI 0.60-1.30). The difference in MED to ED50-100 ratios
      between partial epilepsy (0.82) was not significantly different from that of
      generalised epilepsy (1.08) (p=0.51). CONCLUSION: Photosensitive POP trials are a
      useful tool to quantitatively predict efficacy in epilepsy, and can be useful as
      early and informative indicators in anti-epileptic drug discovery and
      development.

PMID- 24745324
TI  - Putting a face on the prescription opioid epidemic: a case report.
AB  - Skilled clinical decision making in the diagnosis and treatment of chronic pain
      can create unique clinical and ethical challenges, particularly when opioid
      medications are involved. This report presents the case of a pregnant woman who
      sought treatment for an illicit opioid dependence, initiated by opioid analgesic
      treatment of chronic pain. While recognizing opioids' high level of effectiveness
      for pain relief, the case demonstrates the potential harms of opioid medications
      for particular patients. Using a framework informed by medical ethics, the report
      discusses how clinicians might assess the benefits and risks of opioid treatment
      by careful data gathering, knowledge of the evidence base and patient-centered,
      shared decision making.

PMID- 24745325
TI  - Bradycardia related to ribavirin in four pediatric patients with Crimean-Congo
      hemorrhagic fever.
AB  - Crimean-Congo hemorrhagic fever (CCHF) is a potentially fatal fever due to
      infection with the CCHF virus, which belongs to the genus Nairovirus in the
      Bunyaviridae family and causes severe disease in humans, with reported mortality
      rates of 15-70% (Centers for Disease Control and Prevention 1983 ). Humans become
      infected through the bites of ticks, by contact with blood or tissue from viremic
      livestock, or by contact with a patient with CCHF during the acute phase of
      infection (Khan et al. 1997 ). Uysal et al. ( 2012 ) reported bradycardia in a
      patient with CCHF related to ribavirin treatment. We have observed the same side
      effect in four pediatric patients that also resolved with discontinuation of
      ribavirin.

PMID- 24745326
TI  - The emerging landscape of RORgammat biology.
AB  - The transcription factor retinoid-related orphan receptor gamma t (RORgammat) has
      emerged as an exciting target for inflammatory diseases. Xiao et al. (2014) show
      that a new class of RORgammat antagonists can inhibit the inflammatory function
      of T helper 17 cells without altering RORgammat occupancy on its target genes. 

PMID- 24745327
TI  - Prostaglandin E2: the villain in the host response to influenza virus.
AB  - Prostaglandins are lipid mediators that are involved in a plethora of biological
      processes. In this issue of Immunity, Coulombe et al. (2014) report that
      prostaglandin E2 suppresses innate and adaptive immune responses to influenza
      virus.

PMID- 24745328
TI  - Gut reactions: Eosinophils add another string to their bow.
AB  - Eosinophils are found in abundance in the gut. In this issue of Immunity, Chu et
      al. (2014) report that eosinophil-deficient mice have impaired intestinal
      immunoglobulin A production, accompanied by a disrupted mucosal layer and
      alterations in microbiota density and composition.

PMID- 24745329
TI  - Microbial learning lessons: SFB educate the immune system.
AB  - Segmented filamentous bacteria (SFB) contribute to immune-system maturation. In
      this issue of Immunity, Goto et al. (2014) and Lecuyer et al. (2014) provide
      evidence for how SFB induce antigen-specific T helper 17 cells and promote
      development of adaptive immunity at discrete mucosal sites.

PMID- 24745330
TI  - Peeing pentraxins.
AB  - Antimicrobial agents secreted into urine potentially play a powerful role in the
      defense of the urinary tract. In this issue of Immunity, Jaillon et al. (2014)
      describe a role for pentraxin 3 molecules in complementing the host's cellular
      innate immune responses to uropathogens.

PMID- 24745331
TI  - Sepsis: current dogma and new perspectives.
AB  - Sepsis, a clinical syndrome occurring in patients following infection or injury,
      is a leading cause of morbidity and mortality worldwide. Current immunological
      mechanisms do not explain the basis of cellular dysfunction and organ failure,
      the ultimate cause of death. Here we review current dogma and argue that it is
      time to delineate novel immunometabolic and neurophysiological mechanisms
      underlying the altered cellular bioenergetics and failure of epithelial and
      endothelial barriers that produce organ dysfunction and death. These mechanisms
      might hold the key to future therapeutic strategies.

PMID- 24745332
TI  - Small-molecule RORgammat antagonists inhibit T helper 17 cell transcriptional
      network by divergent mechanisms.
AB  - We identified three retinoid-related orphan receptor gamma t (RORgammat)-specific
      inhibitors that suppress T helper 17 (Th17) cell responses, including Th17-cell
      mediated autoimmune disease. We systemically characterized RORgammat binding in
      the presence and absence of drugs with corresponding whole-genome transcriptome
      sequencing. RORgammat acts as a direct activator of Th17 cell signature genes and
      a direct repressor of signature genes from other T cell lineages; its strongest
      transcriptional effects are on cis-regulatory sites containing the RORalpha
      binding motif. RORgammat is central in a densely interconnected regulatory
      network that shapes the balance of T cell differentiation. Here, the three
      inhibitors modulated the RORgammat-dependent transcriptional network to varying
      extents and through distinct mechanisms. Whereas one inhibitor displaced
      RORgammat from its target loci, the other two inhibitors affected transcription
      predominantly without removing DNA binding. Our work illustrates the power of a
      system-scale analysis of transcriptional regulation to characterize potential
      therapeutic compounds that inhibit pathogenic Th17 cells and suppress
      autoimmunity.

PMID- 24745333
TI  - Treg cells expressing the coinhibitory molecule TIGIT selectively inhibit
      proinflammatory Th1 and Th17 cell responses.
AB  - Foxp3(+) T regulatory (Treg) cells regulate immune responses and maintain self
      tolerance. Recent work shows that Treg cells are comprised of many subpopulations
      with specialized regulatory functions. Here we identified Foxp3(+) T cells
      expressing the coinhibitory molecule TIGIT as a distinct Treg cell subset that
      specifically suppresses proinflammatory T helper 1 (Th1) and Th17 cell, but not
      Th2 cell responses. Transcriptional profiling characterized TIGIT(+) Treg cells
      as an activated Treg cell subset with high expression of Treg signature genes.
      Ligation of TIGIT on Treg cells induced expression of the effector molecule
      fibrinogen-like protein 2 (Fgl2), which promoted Treg-cell-mediated suppression
      of T effector cell proliferation. In addition, Fgl2 was necessary to prevent
      suppression of Th2 cytokine production in a model of allergic airway
      inflammation. TIGIT expression therefore identifies a Treg cell subset that
      demonstrates selectivity for suppression of Th1 and Th17 cell but not Th2 cell
      responses.

PMID- 24745334
TI  - Eosinophils promote generation and maintenance of immunoglobulin-A-expressing
      plasma cells and contribute to gut immune homeostasis.
AB  - Although in normal lamina propria (LP) large numbers of eosinophils are present,
      little is known about their role in mucosal immunity at steady state. Here we
      show that eosinophils are needed to maintain immune homeostasis in gut-associated
      tissues. By using eosinophil-deficient DeltadblGATA-1 and PHIL mice or an
      eosinophil-specific depletion model, we found a reduction in immunoglobulin A(+)
      (IgA(+)) plasma cell numbers and in secreted IgA. Eosinophil-deficient mice also
      showed defects in the intestinal mucous shield and alterations in microbiota
      composition in the gut lumen. In addition, TGF-beta-dependent events including
      class switching to IgA in Peyer's patches (PP), the formation of CD103(+) T cells
      including Foxp3(+) regulatory (Treg), and also CD103(+) dendritic cells were
      disturbed. In vitro cultures showed that eosinophils produce factors that promote
      T-independent IgA class switching. Our findings show that eosinophils are
      important players for immune homeostasis in gut-associated tissues and add to
      data suggesting that eosinophils can promote tissue integrity.

PMID- 24745335
TI  - Segmented filamentous bacterium uses secondary and tertiary lymphoid tissues to
      induce gut IgA and specific T helper 17 cell responses.
AB  - Segmented filamentous bacterium (SFB) is a symbiont that drives postnatal
      maturation of gut adaptive immune responses. In contrast to nonpathogenic E.
      coli, SFB stimulated vigorous development of Peyer's patches germinal centers but
      paradoxically induced only a low frequency of specific immunoglobulin A (IgA)
      secreting cells with delayed accumulation of somatic mutations. Moreover,
      blocking Peyer's patch development abolished IgA responses to E. coli, but not to
      SFB. Indeed, SFB stimulated the postnatal development of isolated lymphoid
      follicles and tertiary lymphoid tissue, which substituted for Peyer's patches as
      inductive sites for intestinal IgA and SFB-specific T helper 17 (Th17) cell
      responses. Strikingly, in mice depleted of gut organized lymphoid tissue, SFB
      still induced a substantial but nonspecific intestinal Th17 cell response. These
      results demonstrate that SFB has the remarkable capacity to induce and stimulate
      multiple types of intestinal lymphoid tissues that cooperate to generate potent
      IgA and Th17 cell responses displaying only limited target specificity.

PMID- 24745337
TI  - SFEMG: A piece in the diagnostic puzzle of myasthenia.

PMID- 24745336
TI  - The humoral pattern recognition molecule PTX3 is a key component of innate
      immunity against urinary tract infection.
AB  - Immunity in the urinary tract has distinct and poorly understood
      pathophysiological characteristics and urinary tract infections (UTIs) are
      important causes of morbidity and mortality. We investigated the role of the
      soluble pattern recognition molecule pentraxin 3 (PTX3), a key component of the
      humoral arm of innate immunity, in UTIs. PTX3-deficient mice showed defective
      control of UTIs and exacerbated inflammation. Expression of PTX3 was induced in
      uroepithelial cells by uropathogenic Escherichia coli (UPEC) in a Toll-like
      receptor 4 (TLR4)- and MyD88-dependent manner. PTX3 enhanced UPEC phagocytosis
      and phagosome maturation by neutrophils. PTX3 was detected in urine of UTI
      patients and amounts correlated with disease severity. In cohorts of UTI-prone
      patients, PTX3 gene polymorphisms correlated with susceptibility to acute
      pyelonephritis and cystitis. These results suggest that PTX3 is an essential
      component of innate resistance against UTIs. Thus, the cellular and humoral arms
      of innate immunity exert complementary functions in mediating resistance against
      UTIs.

PMID- 24745338
TI  - Exploring brainstem function in multiple sclerosis by combining brainstem
      reflexes, evoked potentials, clinical and MRI investigations.
AB  - OBJECTIVE: To investigate vestibulo-masseteric (VMR), acoustic-masseteric (AMR),
      vestibulo-collic (VCR) and trigemino-collic (TCR) reflexes in patients with
      multiple sclerosis (MS); to relate abnormalities of brainstem reflexes (BSRs) to
      multimodal evoked potentials (EPs), clinical and Magnetic Resonance Imaging (MRI)
      findings. METHODS: Click-evoked VMR, AMR and VCR were recorded from active
      masseter and sternocleidomastoid muscles, respectively; TCR was recorded from
      active sternocleidomastoid muscles, following electrical stimulation of the
      infraorbital nerve. EPs and MRI were performed with standard techniques. RESULTS:
      Frequencies of abnormal BSRs were: VMR 62.1%, AMR 55.1%, VCR 25.9%, TCR 58.6%.
      Brainstem dysfunction was identified by these tests, combined into a four-reflex
      battery, in 86.9% of cases, by EPs in 82.7%, MRI in 71.7% and clinical
      examination in 37.7% of cases. The sensitivity of paired BSRs/EPs (93.3%) was
      significantly higher than combined MRI/clinical testing (70%) in patients with
      disease duration ?6.4years. BSR alterations significantly correlated with
      clinical, EP and MRI findings. CONCLUSIONS: The four-BSR battery effectively
      increases the performance of standard EPs in early detection of brainstem
      impairment, otherwise undetected by clinical examination and neuroimaging.
      SIGNIFICANCE: Multiple BSR assessment usefully supplements conventional testing
      and monitoring of brainstem function in MS, especially in newly diagnosed
      patients.

PMID- 24745339
TI  - Biomechanical investigation of the supraorbital arch - a transient FEA study on
      the impact of physical blows.
AB  - INTRODUCTION: As fractures of the supraorbital region are far less common than
      midfacial or orbital fractures, a study was initiated to investigate whether fist
      blows could lead to fractures similar to those often seen in the midface.
      METHODS: A detailed skull model and an impactor resembling a fist were created
      and a fist blow to the supraorbital region was simulated. A transient finite
      element analysis was carried out to calculate von Mises stresses, peak force, and
      impact time. RESULTS: Within the contact zone of skull and impactor critical
      stress values could be seen which lay at the lower yield border for potential
      fractures. A second much lower stress zone was depicted in the anterior-medial
      orbital roof. CONCLUSIONS: In this simulation a fist punch, which could generate
      distinct fractures in the midface and naso-ethmoid-orbital region, would only
      reach the limits of a small fracture in the supraorbital region. The reason is
      seen in the strong bony architecture. Much higher forces are needed to create
      severe trauma in the upper face which is supported by clinical findings. Finite
      element analysis is the method of choice to investigate the impact of trauma on
      the human skeleton.

PMID- 24745340
TI  - Development of a de novo arteriovenous malformation after bilateral
      revascularization surgery in a child with moyamoya disease.
AB  - The development of a de novo arteriovenous malformation (AVM) in patients with
      moyamoya disease is extremely rare. A 14-year-old girl developed an AVM in the
      right occipital lobe during the 4-year postoperative period following successful
      bilateral revascularization surgeries. She suffered a transient ischemic attack
      with hemodynamic compromise of the bilateral hemispheres at the age of 10 years.
      Results of an initial examination by 1.5-T MRI and MR angiography satisfied the
      diagnostic criteria of moyamoya disease but failed to detect any vascular
      malformation. Bilateral direct and indirect revascularization surgeries in the
      anterior circulation relieved her symptoms, and she underwent MRI and MR
      angiography follow-up every year after surgery. Serial T2-weighted MRI revealed
      the gradual appearance of flow voids in the right occipital lobe during the
      follow-up period. Magnetic resonance angiography ultimately indicated the
      development of an AVM 4 years after these surgeries when catheter angiography
      confirmed the diagnosis of an AVM in the right occipital lobe. The AVM remained
      asymptomatic, and the patient remained free of cerebrovascular events during the
      time she was observed by the authors. Acquired AVM in moyamoya disease is
      extremely rare, with only 3 pediatric cases including the present case being
      reported in the literature. The development of a de novo AVM in a postoperative
      patient with moyamoya disease appears to be unique, and this case may provide
      insight into the dynamic pathology of AVMs. 

PMID- 24745341
TI  - Altered brain connectivity in sagittal craniosynostosis.
AB  - OBJECT: Sagittal nonsyndromic craniosynostosis (sNSC) is the most common form of
      NSC. The condition is associated with a high prevalence (> 50%) of deficits in
      executive function. The authors employed diffusion tensor imaging (DTI) and
      functional MRI to evaluate whether hypothesized structural and functional
      connectivity differences underlie the observed neurocognitive morbidity of sNSC.
      METHODS: Using a 3-T Siemens Trio MRI system, the authors collected DTI and
      resting-state functional connectivity MRI data in 8 adolescent patients (mean age
      12.3 years) with sNSC that had been previously corrected via total vault
      cranioplasty and 8 control children (mean age 12.3 years) without
      craniosynostosis. Data were analyzed using the FMRIB Software Library and
      BioImageSuite. RESULTS: Analyses of the DTI data revealed white matter
      alterations approaching statistical significance in all supratentorial lobes.
      Statistically significant group differences (sNSC < control group) in mean
      diffusivity were localized to the right supramarginal gyrus. Analysis of the
      resting-state seed in relation to whole-brain data revealed significant increases
      in negative connectivity (anticorrelations) of Brodmann area 8 to the prefrontal
      cortex (Montreal Neurological Institute [MNI] center of mass coordinates [x, y,
      z]: -6, 53, 6) and anterior cingulate cortex (MNI coordinates 6, 43, 14) in the
      sNSC group relative to controls. Furthermore, in the sNSC patients versus
      controls, the Brodmann area 7, 39, and 40 seed had decreased connectivity to left
      angular gyrus (MNI coordinates -31, -61, 34), posterior cingulate cortex (MNI
      coordinates 13, -52, 18), precuneus (MNI coordinates 10, -55, 54), left and right
      parahippocampus (MNI coordinates -13, -52, 2 and MNI coordinates 11, -50, 2,
      respectively), lingual (MNI coordinates -11, -86, -10), and fusiform gyri (MNI
      coordinates -30, -79, -18). Intrinsic connectivity analysis also revealed altered
      connectivity between central nodes in the default mode network in sNSC relative
      to controls; the left and right posterior cingulate cortices (MNI coordinates -5,
      -35, 34 and MNI coordinates 6, -42, 39, respectively) were negatively correlated
      to right hemisphere precuneus (MNI coordinates 6, -71, 46), while the left
      ventromedial prefrontal cortex (MNI coordinates 6, 34, -8) was negatively
      correlated to right middle frontal gyrus (MNI coordinates 40, 4, 33). All group
      comparisons (sNSC vs controls) were conducted at a whole brain-corrected
      threshold of p < 0.05. CONCLUSIONS: This study demonstrates altered neocortical
      structural and functional connectivity in sNSC that may, in part or
      substantially, underlie the neuropsychological deficits commonly reported in this
      population. Future studies combining analysis of multimodal MRI and clinical
      characterization data in larger samples of participants are warranted.

PMID- 24745342
TI  - Currarino syndrome and spinal dysraphism.
AB  - Currarino syndrome is a rare constellation of congenital anomalies characterized
      by the triad of sacral dysgenesis, presacral mass, and anorectal malformation. It
      is frequently associated with other congenital anomalies, often including occult
      spinal dysraphism. Mutations in the MNX1 gene are identified in the majority of
      cases. The authors report a rare case of Currarino syndrome in an infant with
      tethered cord syndrome and a dorsal lipomyelomeningocele continuous with a
      presacral intradural spinal lipoma, in addition to an imperforate anus and a
      scimitar sacrum. They review the literature to highlight patterns of occult
      spinal dysraphism in patients with Currarino syndrome and their relationship to
      tethered cord syndrome. Approximately 60% of the patients with Currarino syndrome
      reported in the literature have an occult spinal dysraphism. Published studies
      suggest that the risk of tethered cord syndrome may be higher among patients with
      a lipoma and lower among those with a teratoma or anterior meningocele. 

PMID- 24745343
TI  - Revascularization and pediatric aneurysm surgery.
AB  - OBJECT: Aneurysms are relatively rare in the pediatric population and tend to
      include a greater proportion of large and giant lesions. A subset of these large
      and giant aneurysms are not amenable to direct surgical clipping and require
      complex treatment strategies and revascularization techniques. There are limited
      data available on the management of these lesions in the pediatric population.
      This study was undertaken to evaluate the outcome of treatment of large and giant
      aneurysms that required microsurgical revascularization and vessel sacrifice in
      this population. METHODS: The authors retrospectively identified all cases in
      which pediatric patients (age < 18 years) with aneurysms were treated using
      cerebral revascularization in combination with other treatment modalities at
      their institution between 1989 and 2013. RESULTS: The authors identified 27
      consecutive patients (19 male and 8 female) with 29 aneurysms. The mean age of
      the patients at the time of treatment was 11.5 years (median 13 years, range 1-17
      years). Five patients presented with subarachnoid hemorrhage, 11 with symptoms
      related to mass effect, 2 with stroke, and 3 with seizures; in 6 cases, the
      aneurysms were incidental findings. Aneurysms were located along the internal
      carotid artery (n = 7), posterior cerebral artery (PCA) (n = 2), anterior
      cerebral artery (n = 2), middle cerebral artery (MCA) (n = 14), basilar artery (n
      = 2), vertebral artery (n = 1), and at the vertebrobasilar junction (n = 1).
      Thirteen were giant aneurysms (45%). The majority of the aneurysms were fusiform
      (n = 19, 66%), followed by saccular (n = 10, 34%). Three cases were previously
      treated using microsurgery (n = 2) or an endovascular procedure (n = 1). A total
      of 28 revascularization procedures were performed, including superficial temporal
      artery (STA) to MCA (n = 6), STA to PCA (n = 1), occipital artery to PCA (n = 1),
      extracranial-intracranial (EC-IC) bypass using radial artery graft (n = 3), EC-IC
      using a saphenous vein graft (n = 7), STA onlay (n = 3), end-to-end anastomosis
      (n = 1), and in situ bypasses (n = 6). Perioperative stroke occurred in 4
      patients, but only one remained dependent (Glasgow Outcome Scale [GOS] score 3).
      At a mean clinical follow-up of 46 months (median 14 months, range 1-232 months),
      26 patients had a good outcome (GOS score 4 or 5). There were no deaths. Five
      patients had documented occlusion of the bypass graft. The majority of aneurysms
      (n = 24) were obliterated at last follow-up. There was a single case of a
      residual aneurysm and one case of recurrence. Angiographic follow-up was
      unavailable in 3 cases. CONCLUSIONS: Cerebral revascularization remains an
      essential tool in the treatment of complex cerebral aneurysms in children.

PMID- 24745344
TI  - [Reconstruction of nasal cartilage defects using a tissue engineering technique
      based on combination of high-density polyethylene and hydrogel].
AB  - AIM OF THE STUDY: Nasal reconstruction remains a challenge for any surgeon. The
      surgical indications for nasal reconstruction after oncologic resection, trauma
      or as part of cosmetic rhinoplasty, are steadily increasing. The current attitude
      for reconstruction is the use of autologous cartilage grafts of various origins
      (septal, ear or rib) trying to restore a physiological anatomy but their quantity
      is limited. Thus, in order to produce an implantable cartilaginous model, we
      developed a study protocol involving human nasal chondrocytes, growth factors and
      a composite biomaterial and studied at the molecular, cellular and tissue level
      the phenotype of the chondrocytes cultured in this model. MATERIALS AND METHODS:
      After extraction of chondrocytes and their amplification on plastic, the cells
      were cultured for 15 days either in monolayer or within an agarose hydrogel or a
      composite biomaterial (agarose/high density polyethylene: Medpor((r))) in the
      presence or not of a cocktail of soluble factors (BIT): bone morphogenetic
      protein-2 (BMP-2), insulin and triiodothyronine (T3). The quality of the
      chondrocyte phenotype was analyzed by PCR, western blotting and
      immunohistochemistry. RESULTS: During their amplification in monolayer,
      chondrocytes dedifferentiate. However, our results show that the BIT cocktail
      induces redifferentiation of chondrocytes cultured in agarose/Medpor with
      synthesis of mature chondrogenic markers. Thereby, chondrocytes associated with
      the agarose hydrogel will colonize Medpor and synthesize an extracellular matrix
      characteristic of nasal cartilage. CONCLUSION: This nasal cartilage tissue
      engineering protocol provides the first interesting results for nasal
      reconstruction.

PMID- 24745345
TI  - PSA-PSMA profiles and their impact on sera PSA levels and angiogenic activity in
      hyperplasia and human prostate cancer.
AB  - AIM: The relevance of prostate specific antigen (PSA)-prostate specific membrane
      antigen (PSMA) profiles in pathologic prostate (hyperplasia and cancer) has not
      been fully understood. The aim of this study is to investigate the impact of PSA
      PSMA profiles on sera PSA levels and angiogenic activity in benign prostate
      hyperplasia (BPH) and prostate carcinoma (PC). PATIENTS AND METHODS: The study
      has been carried out in 6 normal prostate (NP), 29 BPH and 33 PC with dominant
      Gleason grade>8. Immunohistochemical analysis has been performed. Monoclonal
      antibodies 3E6 and ER-PR8 have been used to assess PSMA and PSA expression
      respectively. The evaluation of angiogenesis has been made by CD34 immune marker.
      Serum levels of PSA have been assayed by Immulite autoanalyser. RESULTS: The
      study of each protein separately among sera PSA levels showed that PSMA
      expression and angiogenic activity have the highest intensity in PC patients with
      serum PSA levels>20 ng/mL. Nevertheless, the lowest tissue PSA expression was
      found in PC patients with this latter sera PSA group. The most relevant results
      showed that in PC patients (PSA+, PSMA+) and (PSA-, PSMA+) profile were found to
      be inversely related to sera PSA levels. In PC patients, a high immunoexpression
      of (PSA+, PSMA+) profile has detected in the sera PSA group>20 ng/mL; whereas a
      high immunoexpression of (PSA-, PSMA+) profile was detected in the sera PSA group
      between 0 and 4 ng/mL. The highest angiogenic activity was found in PC patients
      with (PSA+, PSMA+) profile. CONCLUSIONS: Our findings clearly have supported the
      feasibility of PSA-PSMA profiles to improve in vivo diagnostic and therapeutic
      approaches in prostate cancer patients.

PMID- 24745346
TI  - Inhibition of autophagy enhances the cytotoxic effect of PA-MSHA in breast
      cancer.
AB  - BACKGROUND: PA-MSHA, a genetically engineered Pseudomonas aeruginosa (PA) strain,
      is currently under investigation as a new anti-cancer drug. It can induce cell
      cycle arrest and apoptosis in different human cancer cells, including hormone
      receptor negative breast cancer cells. However, the underlying mechanism of tumor
      lethality mediated by PA-MSHA remains to be fully investigated. METHODS: The
      effect of PA-MSHA on human hormone receptor negative breast cancer cells was
      analyzed by morphological measurement, western blot, cell proliferation assay and
      mouse xenograft model. RESULTS: PA-MSHA was found to induce endoplasmic reticulum
      (ER) stress in breast cancer cell lines through the IRE1 signaling pathway.
      Inhibiting autophagy potentiated the cytotoxic effect of PA-MSHA while treating
      breast cancer cell lines. In mouse xenograft model, PA-MSHA produced more
      pronounced tumor suppression in mice inoculated with IRE1 gene knockdown. MDA-MB
      231HM cells. CONCLUSIONS: These findings demonstrated inhibiting autophagy
      together with PA-MSHA might be a promising therapeutic strategy in treating
      hormone receptor negative breast cancer cells.

PMID- 24745347
TI  - Randomized clinical trial to evaluate the pathogenicity of Bibersteinia trehalosi
      in respiratory disease among calves.
AB  - BACKGROUND: Bibersteinia trehalosi causes respiratory disease in ruminants
      particularly in wild and domestic sheep. Recently, there has been an increased
      number of B. trehalosi isolates obtained from diagnostic samples from bovine
      respiratory disease cases. This study evaluated the role of B. trehalosi in
      bovine respiratory disease using an intra-tracheal inoculation model in calves.
      Thirty six cross bred 2-3 month old dairy calves were inoculated intra-tracheally
      with either leukotoxin negative B. trehalosi, leukotoxin positive B. trehalosi
      isolate, Mannheimia haemolytica, a combination of leukotoxin negative B.
      trehalosi and M. haemolytica or negative control. Calves were euthanized and
      necropsy performed on day 10 of study. RESULTS: B. trehalosi inoculated calves
      did not have increased lung involvement compared to control calves. Additionally,
      B. trehalosi was only cultured once from the lungs of inoculated calves at
      necropsy. CONCLUSIONS: Based on these findings B. trehalosi may not be a primary
      pathogen of respiratory disease in cattle. Culture of B. trehalosi from
      diagnostic submissions should not be immediately identified as a primary cause of
      respiratory disease.

PMID- 24745348
TI  - Physical fitness among urban and rural Ecuadorian adolescents and its association
      with blood lipids: a cross sectional study.
AB  - BACKGROUND: Physical fitness has been proposed as a marker for health during
      adolescence. Currently, little is known about physical fitness and its
      association with blood lipid profile in adolescents from low and middle-income
      countries. The aim of this study is therefore to assess physical fitness among
      urban and rural adolescents and its associations with blood lipid profile in a
      middle-income country. METHODS: A cross-sectional study was conducted between
      January 2008 and April 2009 in 648 Ecuadorian adolescents (52.3% boys), aged 11
      to 15 years, attending secondary schools in Cuenca (urban n = 490) and Nabon
      (rural n = 158). Data collection included anthropometric measures, application of
      the EUROFIT battery, dietary intake (2-day 24 h recall), socio-demographic
      characteristics, and blood samples from a subsample (n = 301). The FITNESGRAM
      standards were used to evaluate fitness. The associations of fitness and
      residential location with blood lipid profile were assessed by linear and
      logistic regression after adjusting for confounding factors. RESULTS: The
      majority (59%) of the adolescents exhibited low levels of aerobic capacity as
      defined by the FITNESSGRAM standards. Urban adolescents had significantly higher
      mean scores in five EUROFIT tests (20 m shuttle, speed shuttle run, plate
      tapping, sit-up and vertical jump) and significantly most favorable improved
      plasma lipid profile (triglycerides and HDL) as compared to rural adolescents.
      There was a weak association between blood lipid profile and physical fitness in
      both urban and rural adolescents, even after adjustment for confounding factors.
      CONCLUSIONS: Physical fitness, in our sample of Ecuadorian adolescents, was
      generally poor. Urban adolescents had better physical fitness and blood lipid
      profiles than rural adolescents. The differences in fitness did not explain those
      in blood lipid profile between urban and rural adolescents.

PMID- 24745349
TI  - Central nervous system toxicities of chemotherapeutic agents.
AB  - Although there has been a significant progress in the recognition and management
      of the most common chemotherapy side effects, there is limited data on CNS
      toxicities. Since CNS toxicities can cause significant morbidity and delay or
      interruption of potentially effective therapies, there is a need for better
      understanding, early detection, prompt discontinuation of the offending drug, and
      use of antidotes when available. This review describes neurological toxicities
      from some of the commonly used chemotherapy agents. 

PMID- 24745350
TI  - Analysis and prediction of Ross River virus transmission in New South Wales,
      Australia.
AB  - BACKGROUND: Ross River virus (RRV) disease is the most widespread mosquito-borne
      disease in Australia. The disease is maintained in enzootic cycles between
      mosquitoes and reservoir hosts. During outbreaks and in endemic regions, RRV
      transmission can be sustained between vectors and reservoir hosts in zoonotic
      cycles with spillover to humans. Symptoms include arthritis, rash, fever and
      fatigue and can persist for several months. The prevalence and associated
      morbidity make this disease a medically and economically important mosquito-borne
      disease in Australia. METHODS: Climate, environment, and RRV vector and reservoir
      host information were used to develop predictive models in four regions in NSW
      over a 13-year period (1991-2004). Polynomial distributed lag (PDL) models were
      used to explore long-term influences of up to 2 years ago that could be related
      to RRV activity. RESULTS: Each regional model consisted of a unique combination
      of predictors for RRV disease highlighting the differences in the disease ecology
      and epidemiology in New South Wales (NSW). Events up to 2 years before were found
      to influence RRV activity. The shorter-term associations may reflect conditions
      that promote virus amplification in RRV vectors whereas long-term associations
      may reflect RRV reservoir host breeding and herd immunity. The models indicate an
      association between host populations and RRV disease, lagged by 24 months,
      suggesting two or more generations of susceptible juveniles may be necessary for
      an outbreak. Model sensitivities ranged from 60.4% to 73.1%, and model
      specificities ranged from 57.9% to 90.7%. This was the first study to include
      reservoir host data into statistical RRV models; the inclusion of host parameters
      was found to improve model fit significantly. CONCLUSION: The research presents
      the novel use of a combination of climate, environment, and RRV vector and
      reservoir host information in statistical predictive models. The models have
      potential for public health decision-making.

PMID- 24745351
TI  - Time of symptom onset and value of myocardial blush and infarct size on prognosis
      in patients with ST-elevation myocardial infarction.
AB  - In patients with ST-segment elevation myocardial infarction (STEMI), the time of
      onset of ischemia has been associated with myocardial infarction (MI) size.
      Myocardial blush grade (MBG) reflects myocardial response to ischemia/reperfusion
      injury, which may differ according to time of the day. The aim of our study was
      to explore the 24-hour variation in MBG and MI size in relation to outcomes in
      STEMI patients. A retrospective multicenter analysis of 6970 STEMI patients was
      performed. Time of onset of STEMI was divided into four 6-hour periods. STEMI
      patients have a significant 24-hour pattern in onset of symptoms, with peak onset
      around 09:00 hour. Ischemic time was longest and MI size, estimated by peak
      creatine kinase concentration, was largest in patients with STEMI onset between
      00:00 and 06:00 hours. Both MBG and MI size were independently associated with
      mortality. Time of onset of STEMI was not independently associated with mortality
      when corrected for baseline and procedural factors. Interestingly, patients
      presenting with low MBG between 00:00 and 06:00 hours had a better prognosis
      compared to other groups. In conclusion, patients with symptom onset between
      00:00 and 06:00 hours have longer ischemic time and consequently larger MI size.
      However, this does not translate into a higher mortality in this group. In
      addition, patients with failed reperfusion presenting in the early morning hours
      have better prognosis, suggesting a 24-hour pattern in myocardial protection.

PMID- 24745352
TI  - Rotational vertebral artery occlusion secondary to adjacent-level degeneration
      following anterior cervical discectomy and fusion.
AB  - Rotational vertebral artery occlusion (RVAO), or bow hunter's syndrome, most
      often occurs at the C1-2 level on physiological head rotation. It presents with
      symptoms of vertebrobasilar insufficiency (VBI). Several previously published
      studies have reported on subaxial sites of vertebral artery (VA) compression by
      head rotation. The authors report a case of subaxial spine RVAO due to adjacent
      segment degeneration. A 52-year-old man presented with dizziness when rotating
      his head to the left. Twenty years earlier, he had undergone a C4-5 anterior
      cervical discectomy and fusion (ACDF) for a herniated disc. Imaging studies
      including a dynamic CT angiography and dynamic catheter angiography revealed
      occlusion of the left VA at the C3-4 level when the patient turned his head to
      the left, in the setting of an aberrant vertebrobasilar system. Successful
      treatment was achieved by surgical decompression of the left VA and C3-4 ACDF.
      Expedited diagnosis and treatment are dependent on the recognition of this
      unusual manifestation of RVAO, especially when patients present with nonspecific
      symptoms of VBI. 

PMID- 24745353
TI  - Direct posterior reduction in a case of posttraumatic irreducible lateral
      atlantoaxial dislocation.
AB  - Posttraumatic true irreducible C1-2 lateral dislocation is rare. The mechanism of
      injury is likely to be different for this kind of dislocation. The management of
      such an injury and the technique for direct posterior reduction remain unclear
      because of its rarity. The authors describe the case of a 34-year-old man who
      sustained injury in a vehicular accident, leading to neck pain. Radiological
      studies revealed fixed right lateral and posterior C1-2 dislocation. Direct
      posterior open reduction was achieved by distracting the facets and rotating them
      in a counterclockwise direction. Care was taken to avoid direct or indirect
      injury to the vertebral arteries. Segmental C1-2 fusion was performed.
      Distraction with lateral extension injury possibly gives rise to this unique
      fracture dislocation. Preoperative imaging including angiography for vertebral
      arteries helps in defining the cause of fixity and in surgical planning. Direct
      posterior reduction is possible in such fixed C1-2 lateral dislocation,
      circumventing transoral surgery-provided the facets are preserved. 

PMID- 24745354
TI  - Spinal dural arteriovenous fistula associated with L-4 isthmic spondylolisthesis.
AB  - The authors describe a case of a 79-year-old man with a lumbar spinal dural
      arteriovenous fistula (DAVF) and isthmic spondylolisthesis at the same level. The
      patient's thoracic spine MRI study demonstrated swelling and increased T2 signal
      in the spinal cord and regional dilated perimedullary vessels. Lumbar spine MRI
      showed L-4 isthmic spondylolisthesis with severe bilateral L4-5 foraminal
      stenoses. Spinal angiography revealed a fistulous connection at the left L-4
      nerve root sleeve between perimedullary veins and a dural branch of the L-4
      radicular artery. Based on previous reports about secondary spinal DAVFs, the
      abnormal vascular communication likely developed secondary to the microtrauma and
      inflammation on the left L-4 nerve root sleeve, which was attributable to the
      isthmic spondylolisthesis. The authors performed disconnection of the
      arteriovenous shunt as well as an L4-5 decompression and posterior instrumented
      fusion with pedicle screws. The patient's postoperative course was uneventful,
      and he improved neurologically. It is important to bear in mind that a spinal
      DAVF may develop as a consequence of any sort of trauma or inflammation involving
      nerve roots. One should consider the concomitant treatment of both the spinal
      DAVF and the underlying pathology that may have given rise to the spinal DAVF. 

PMID- 24745355
TI  - Minimally invasive versus open transforaminal lumbar interbody fusion: comparison
      of clinical outcomes among obese patients.
AB  - OBJECT: Minimally invasive (MI) transforaminal lumbar interbody fusion (TLIF) has
      been demonstrated in previous studies to offer improvement in pain and function
      comparable to those provided by the open surgical approach. However, comparative
      studies in the obese population are scarce, and it is possible that obese
      patients may respond differently to these two approaches. In this study, the
      authors compared the clinical benefit of open and MI TLIF in obese patients.
      METHODS: The authors conducted a retrospective cohort study based on review of
      electronic medical records at a single institution. Eligible patients had a body
      mass index (BMI) >= 30 kg/m(2), were >= 18 years of age, underwent single-level
      TLIF between 2007 and 2011, and outcome was assessed at a minimum 6 months
      postoperatively. The authors categorized patients according to surgical approach
      (open vs MI TLIF). Outcome measures included postoperative improvement in visual
      analog scale (VAS), Oswestry Disability Index (ODI), estimated blood loss (EBL),
      and hospital length of stay (LOS). RESULTS: A total 74 patients (21 open and 53
      MI TLIF) were studied. Groups had similar baseline characteristics. The median
      BMI was 34.4 kg/m(2) (interquartile range 31.6-37.5 kg/m(2)). The mean follow-up
      time was 30 months (range 6.5-77 months). The mean improvement in VAS score was
      2.8 (95% CI 1.9-3.8) for the open group (n = 21) and 2.4 (95% CI 1.8-3.1) for the
      MI group (n = 53), which did not significantly differ (unadjusted, p = 0.49;
      adjusted, p = 0.51). The mean improvement in ODI scores was 13 (95% CI 3-23) for
      the open group (n = 14) and 15 (95% CI 8-22) for the MI group (n = 45), with no
      significant difference according to approach (unadjusted, p = 0.82; adjusted, p =
      0.68). After stratifying by BMI (< 35 kg/m(2) and >= 35 kg/m(2)), there was still
      no difference in either VAS or ODI improvement between the approaches (both
      unadjusted and adjusted, p > 0.05). Complications and EBL were greater for the
      open group than for the MI group (p < 0.05). CONCLUSIONS: Obese patients
      experienced clinically and statistically significant improvement in both pain and
      function after undergoing either open or MI TLIF. Patients achieved similar
      clinical benefit whether they underwent an open or MI approach. However, patients
      in the MI group experienced significantly decreased operative blood loss and
      complications than their counterparts in the open group.

PMID- 24745356
TI  - The efficacy of self-management programmes for increasing physical activity in
      community-dwelling adults with acquired brain injury (ABI): a systematic review.
AB  - BACKGROUND: Acquired brain injury (ABI), often arising from stroke or trauma, is
      a common cause of long-term disability, physical inactivity and poor health
      outcomes globally. Individuals with ABI face many barriers to increasing physical
      activity, such as impaired mobility, access to services and knowledge regarding
      management of physical activity. Self-management programmes aim to build skills
      to enable an individual to manage their condition, including their physical
      activity levels, over a long period of time. Programme delivery modes can include
      traditional face-to-face methods, or remote delivery, such as via the Internet.
      However, it is unknown how effective these programmes are at specifically
      improving physical activity in community-dwelling adults with ABI, or how
      effective and acceptable remote delivery of self-management programmes is for
      this population. METHODS/DESIGN: We will conduct a comprehensive search for
      articles indexed on MEDLINE, EMBASE, CINAHL, PsychINFO, AMED, Cochrane Central
      Register of Controlled Trials (CENTRAL), PEDro and Science Citation Index
      Expanded (SCI-EXPANDED) databases that assess the efficacy of a self-management
      intervention, which aims to enhance levels of physical activity in adults living
      in the community with ABI. Two independent reviewers will screen studies for
      eligibility, assess risk of bias, and extract relevant data. Where possible, a
      meta-analysis will be performed to calculate the overall effect size of self
      management interventions on physical activity levels and on outcomes associated
      with physical activity. A comparison will also be made between face-to-face and
      remote delivery modes of self-management programmes, in order to examine efficacy
      and acceptability. A content analysis of self-management programmes will also be
      conducted to compare aspects of the intervention that are associated with more
      favourable outcomes. DISCUSSION: This systematic review aims to review the
      efficacy of self-management programmes aimed at increasing physical activity
      levels in adults living in the community with ABI, and the efficacy and
      acceptability of remote delivery of these programmes. If effective, remote
      delivery of self-management programmes may offer an alternative way to overcome
      barriers and empower individuals with ABI to increase their levels of physical
      activity, improving health and general wellbeing. TRIAL REGISTRATION: Our
      protocol has been registered on PROSPERO 2013: CRD42013006748.

PMID- 24745357
TI  - Synthesis of PCDTBT-based fluorinated polymers for high open-circuit voltage in
      organic photovoltaics: towards an understanding of relationships between polymer
      energy levels engineering and ideal morphology control.
AB  - The introduction of fluorine (F) atoms onto conjugated polymer backbone has
      verified to be an effective way to enhance the overall performance of polymer
      based bulk-heterojunction (BHJ) solar cells, but the underlying working
      principles are not yet fully uncovered. As our attempt to further understand the
      impact of F, herein we have reported two novel fluorinated analogues of PCDTBT,
      namely, PCDTFBT (1F) and PCDT2FBT (2F), through inclusion of either one or two F
      atoms into the benzothiadiazole (BT) unit of the polymer backbone and the
      characterization of their physical properties, especially their performance in
      solar cells. Together with a profound effect of fluorination on the optical
      property, nature of charge transport, and molecular organization, F atoms are
      effective in lowering both the HOMO and LUMO levels of the polymers without a
      large change in the energy bandgaps. PCDTFBT-based BHJ solar cell shows a power
      conversion efficiency (PCE) of 3.96 % with high open-circuit voltage (VOC) of
      0.95 V, mainly due to the deep HOMO level (-5.54 eV). To the best of our
      knowledge, the resulting VOC is comparable to the record VOC values in single
      junction devices. Furthermore, to our delight, the best PCDTFBT-based device,
      prepared using 2 % v/v diphenyl ether (DPE) additive, reaches the PCE of 4.29 %.
      On the other hand, doubly-fluorinated polymer PCDT2FBT shows the only moderate
      PCE of 2.07 % with a decrease in VOC (0.88 V), in spite of the further lowering
      of the HOMO level (-5.67 eV) with raising the number of F atoms. Thus, our
      results highlight that an improvement in efficiency by tuning the energy levels
      of the polymers by means of molecular design can be expected only if their truly
      optimized morphologies with fullerene in BHJ systems are materialized. 

PMID- 24745358
TI  - Molecular dynamics simulations of turbostratic dry and hydrated montmorillonite
      with intercalated carbon dioxide.
AB  - Molecular dynamics simulations using classical force fields were carried out to
      study energetic and structural properties of rotationally disordered clay mineral
      water-CO2 systems at pressure and temperature relevant to geological carbon
      storage. The simulations show that turbostratic stacking of hydrated Na- and Ca
      montmorillonite and hydrated montmorillonite with intercalated carbon dioxide is
      an energetically demanding process accompanied by an increase in the interlayer
      spacing. On the other hand, rotational disordering of dry or nearly dry smectite
      systems can be energetically favorable. The distributions of interlayer species
      are calculated as a function of the rotational angle between adjacent clay
      layers. 

PMID- 24745359
TI  - Toxoplasmosis in natural populations of ungulates in France: prevalence and
      spatiotemporal variations.
AB  - Toxoplasmosis is characterized by a complex epidemiology. The risk of infection
      for humans depends on their contact with infective oocysts in a contaminated
      environment and on the amount of tissue cysts located within consumed meat.
      Unfortunately, the prevalence of tissue cysts is largely unknown for game
      species. Although herbivorous game species are a source of infection for humans,
      the level of infection found in wildlife can also be used to estimate
      environmental contamination. The aim of this study was to estimate the prevalence
      of Toxoplasma gondii infection and analyze its temporal dynamics in one
      population of chamois (Rupicapra rupicapra), one of mouflon (Ovis gmelini
      musimon), and two of roe deer (Capreolus capreolus) in France, surveyed during a
      period of 6 to 28 years. Taking into account individual risk factors, we
      specifically analyzed the relationship between T. gondii prevalence and
      meteorological conditions that may influence oocyst survival. Serum samples from
      101 chamois, 143 mouflons, and 1155 roe deer were tested for antibodies against
      T. gondii using the modified agglutination test (MAT), an enzyme-linked
      immunosorbent assay (ELISA) assay, or both. Using MAT with a threshold of 1:6,
      seroprevalence was 14.7% in mouflon, 16.8% in chamois, and 43.7% in roe deer. In
      mouflon and roe deer, seroprevalence was positively correlated with age and/or
      body mass, in accordance with the hypothesis that antibodies have long-term
      persistence. In roe deer, seropositivity differed between the two populations and
      changed linearly over time between 1983 and 2010, increasing by a factor 1.75
      every 10 years. Moreover, in this species, the highest prevalences were found
      during dry and cold years or during warm and moist years, depending on the
      population. Our results suggest that the risk for people to acquire infection
      through game meat increases over time, but with high variability according to the
      population of origin and meteorological conditions of the year.

PMID- 24745360
TI  - Is research a waste of money and time?

PMID- 24745361
TI  - A cure for HIV: is it in sight?
AB  - HIV is a devastating disease affecting millions of people worldwide despite the
      advent of successful antiretroviral therapy (ART). However, ART does not result
      in a cure and has to be taken for life. Accordingly, researchers are turning
      towards cure efforts, particularly in the light of two patients whose HIV has
      been seemingly eradicated. Numerous approaches and strategies have been
      considered for curing HIV, but no scalable and safe solution has yet been
      reached. With newly discovered difficulties in measuring the HIV reservoir, the
      main barrier to a cure, the only true test of cure is to stop ART and see whether
      the virus becomes detectable. However, it is possible that this treatment
      interruption may be associated with certain risks for patients. Here, we compare
      the current major approaches and recent advances for curing HIV, as well as
      discuss ways of evaluating HIV cure and the safety concerns involved. 

PMID- 24745362
TI  - The effects of individual, family and environmental factors on physical activity
      levels in children: a cross-sectional study.
AB  - BACKGROUND: Physical activity plays an important role in optimising physical and
      mental health during childhood, adolescence, and throughout adult life. This
      study aims to identify individual, family and environmental factors that
      determine physical activity levels in a population sample of children in Ireland.
      METHODS: Cross-sectional analysis of the first wave (2008) of the nationally
      representative Growing Up in Ireland study. A two-stage clustered sampling method
      was used where national schools served as the primary sampling unit (response
      rate: 82%) and age eligible children from participating schools were the
      secondary units (response rate: 57%). Parent reported child physical activity
      levels and potential covariates (parent and child reported) include favourite
      hobby, total screen time, sports participation and child body mass index
      (measured by trained researcher). Univariate and multivariate multinomial
      logistic regression (forward block entry) examined the association between
      individual, family and environmental level factors and physical activity levels.
      RESULTS: The children (N = 8,568) were classified as achieving low (25%),
      moderate (20%) or high (55%) physical activity levels. In the fully adjusted
      model, male gender (OR 1.64 [95% CI: 1.34-2.01]), having an active favourite
      hobby (OR 1.65 [95% CI: 1.31-2.08]) and membership of sports or fitness team (OR
      1.90 [95% CI: 1.48-2.45]) were significantly associated with being in the high
      physical activity group. Exceeding two hours total screen time (OR 0.66 [95% CI:
      0.52-0.85]), being overweight (OR 0.41 [95%CI: 0.27-0.61]; or obese (OR 0.68
      [95%CI: 0.54-0.86]) were significantly associated with decreased odds of being in
      the high physical activity group. CONCLUSIONS: Individual level factors appear to
      predict PA levels when considered in the multiple domains. Future research should
      aim to use more robust objective measures to explore the usefulness of the
      interconnect that exists across these domains. In particular how the family and
      environmental settings could be useful facilitators for consistent individual
      level factors such as sports participation.

PMID- 24745363
TI  - Precision and accuracy of TearLab osmometer in measuring osmolarity of salt
      solutions.
AB  - PURPOSE: The purpose of this study was to examine the inherent precision and
      accuracy of TearLab Osmolarity System using salt solutions, including solutions
      of very high osmolarity (>360 mOsm/L). MATERIALS AND METHODS: Ten salt solutions
      with osmolarity between 286 mOsm/L and 394 mOsm/L (increments of 12 mOsm/L) plus
      an additional solution of 400 mOsm/L were tested twice on both the TearLab
      osmometer and a freezing point depression osmometer. For precision, we compared
      the two repeated osmolarity measurements of 11 solutions obtained from TearLab.
      For accuracy, we compared the averaged osmolarity measurements obtained from
      TearLab to those from the freezing point depression osmometer. For both precision
      and accuracy, Bland-Altman test of agreement was used. RESULTS: For precision,
      the upper 95% limit of agreement was 4.7 mOsm/L, and the lower 95% limit of
      agreement was -7.1 mOsm/L. The repeatability coefficient was 5.9 mOsm/L. For
      accuracy, the upper 95% limit of agreement was 4.8 mOsm/L and the lower 95% limit
      of agreement was -5.3 mOsm/L. CONCLUSIONS: The present study is the first study
      to demonstrate that the TearLab in situ osmometer can precisely and accurately
      measure osmolarity of salt solutions, including those with very high osmolarity.
      Future studies to evaluate the precision and the accuracy of the machine in
      measuring complex fluids, such as tears, need to be done, and the clinical
      significance of measuring tear osmolarity in patients needs to be further
      determined.

PMID- 24745364
TI  - Protective effects of apocynin on atrial electrical remodeling and oxidative
      stress in a rabbit rapid atrial pacing model.
AB  - It has been proposed that apocynin might be used in the prevention and management
      of atrial fibrillation (AF). The purpose of this study was to investigate the
      effects of apocynin on atrial electrical remodeling and oxidative stress promoted
      by rapid atrial pacing (RAP) in rabbits. New Zealand white rabbits were subjected
      to RAP with or without apocynin treatment. Serial electrophysiological studies
      (EPS) were performed at baseline and every half hour after RAP onset. Superoxide
      dismutase (SOD) and lactate dehydrogenase (LDH) activities and Ca2+ content in
      tissue homogenates of both atria were assayed after EPS. In the RAP group but not
      in the sham-operated and RAP with apocynin groups, atrial effective refractory
      periods (AERPs) at cycle length of 200 and 150 ms shortened most clearly by 20.8
      +/- 10.2 ms at 3 h (P < 0.001) and by 12.8 +/- 11.1 ms at 2 h (P < 0.05)
      respectively, and AERP rate adaptation decreased to minus values. Higher AF
      inducibility (66.7%) and longer AF duration (an average of 37.8 min) were
      presented in the RAP group. Compared with the other groups, SOD activity was
      lower, and LDH activity and Ca2+ content were higher in the RAP group. Similar
      differences were not found between the sham-operated and the RAP with apocynin
      treatment groups. These data show that apocynin attenuates the development of
      atrial electrical remodeling in a short period of 3-hour RAP, and reduces RAP
      mediated inducibility and duration of AF in this model. 

PMID- 24745366
TI  - Modulation of pro-inflammatory activation of monocytes and dendritic cells by aza
      bis-phosphonate dendrimer as an experimental therapeutic agent.
AB  - INTRODUCTION: Our objective was to assess the capacity of dendrimer aza-bis
      phosphonate (ABP) to modulate phenotype of monocytes (Mo) and monocytes derived
      dendritic cells (MoDC) activated in response to toll-like receptor 4 (TLR4) and
      interferon gamma (IFN- gamma) stimulation. METHODS: Mo (n = 12) and MoDC (n = 11)
      from peripheral blood of healthy donors were prepared. Cells were preincubated or
      not for 1 hour with dendrimer ABP, then incubated with lipopolysaccharide (LPS;
      as a TLR4 ligand) and (IFN-gamma) for 38 hours. Secretion of tumor necrosis
      factor alpha (TNFalpha), interleukin (IL) -1, IL-6, IL-12, IL-10 and IL-23 in the
      culture medium was measured by enzyme-linked immunosorbent assay (ELISA) and
      Cytokine Bead Array. Differentiation and subsequent maturation of MoDC from nine
      donors in the presence of LPS were analyzed by flow cytometry using CD80, CD86,
      CD83 and CD1a surface expression as markers. RESULTS: Mo and MoDC were orientated
      to a pro-inflammatory state. In activated Mo, TNFalpha, IL-1beta and IL-23 levels
      were significantly lower after prior incubation with dendrimer ABP. In activated
      MoDC, dendrimer ABP promoted IL-10 secretion while decreasing dramatically the
      level of IL-12. TNFalpha and IL-6 secretion were significantly lower in the
      presence of dendrimer ABP. LPS driven maturation of MoDC was impaired by
      dendrimer ABP treatment, as attested by the significantly lower expression of
      CD80 and CD86. CONCLUSION: Our data indicate that dendrimer ABP possesses
      immunomodulatory properties on human Mo and MoDC, in TLR4 + IFN-gamma stimulation
      model, by inducing M2 alternative activation of Mo and promoting tolerogenic
      MoDC.

PMID- 24745367
TI  - Titania composite microspheres endowed with a size-exclusive effect toward the
      highly specific revelation of phosphopeptidome.
AB  - The efficient isolation of low-abundance phosphopeptides from complicated
      biological samples containing a significant quantity of nonphosphopeptides and
      proteins is essential for phosphopeptidome research but remains a great
      challenge. In this Article, magnetic composite microspheres comprising a magnetic
      colloidal nanocrystal cluster core and a mesoporous titania shell with an average
      pore diameter of 3.4 nm were modified by directly coating an amorphous titania
      shell onto the magnetite core, followed by converting the amorphous titania shell
      into a crystalline structure via a hydrothermal process at 80  degrees C. The as
      prepared magnetic mesoporous titania microspheres possess a remarkable specific
      surface area that is as high as 603.5 m2/g, which is an appropriate pore size
      with a narrow size distribution and a high magnetic responsiveness. These
      outstanding features imply that the composite microspheres exhibit extraordinary
      performance in phosphopeptidome research, including high specificity toward
      phosphopeptides, an excellent size-exclusion effect against phosphoproteins,
      exceptional enrichment capacity, and efficient separation from mixtures.
      Encouraged by the experimental results, we employed this method to investigate
      the phosphopeptidome of snake venom for the first time. A total of 35
      phosphopeptides was identified from the snake venom from the family Viperidae,
      accounting for 75% of the total identified peptides. This result represents the
      largest data set of the phosphopeptidome in snake venom from the family
      Viperidae.

PMID- 24745368
TI  - Assessing the accuracy of new geminal-based approaches.
AB  - We present a systematic theoretical study on the dissociation of diatomic
      molecules and their spectroscopic constants using our recently presented geminal
      based wave function ansatze. Specifically, the performance of the antisymmetric
      product of rank two geminals (APr2G), the antisymmetric product of 1-reference
      orbital geminals (AP1roG) and its orbital-optimized variant (OO-AP1roG) are
      assessed against standard quantum chemistry methods. Our study indicates that
      these new geminal-based approaches provide a cheap, robust, and accurate
      alternative for the description of bond-breaking processes in closed-shell
      systems requiring only mean-field-like computational cost. In particular, the
      spectroscopic constants obtained from OO-AP1roG are in very good agreement with
      reference theoretical and experimental data. 

PMID- 24745365
TI  - Advances in plasmonic technologies for point of care applications.

PMID- 24745369
TI  - Adherence to physical activity guidelines in older adults, using objectively
      measured physical activity in a population-based study.
AB  - BACKGROUND: Physical activity (PA) levels in older adults decline with age. The
      prevalence and correlates of adherence to current UK PA guidelines in older
      adults has not been studied using objectively measured PA, which can examine
      precisely whether PA is carried out in bouts of specified length and intensity.
      METHODS: Free living men and women aged 70-93 years from 25 towns in the United
      Kingdom, participating in parallel on-going population based cohort studies were
      invited (by post) to wear a GT3x accelerometer over the hip for one week in 2010
      12. Adherence to UK PA guidelines was defined as >=150 minutes/week of moderate
      or vigorous PA (MVPA) in bouts of >=10 minutes; the effect of different
      intensities and durations were examined. RESULTS: 1593 men and 857 women
      participated (responses 51% and 29% respectively). 15% men and 10% women achieved
      >=150 minutes/week of MVPA (defined as >1040 cpm) in bouts lasting >=10 minutes.
      With MVPA defined as >1952 cpm, prevalences were 7% and 3% respectively. Those
      adhering to guidelines were younger, had fewer chronic health conditions, less
      depression, less severe mobility limitations, but higher exercise self-efficacy
      and exercise outcomes expectations. They rated their local environment more
      highly for social activities and leisure facilities, having somewhere nice to go
      for a walk and feeling safe after dark, They left the house on more days per
      week, were more likely to use active transport (cycle or walk) and to walk a dog
      regularly. CONCLUSIONS: Few older adults attain current PA guidelines. Health
      promotion to extend the duration of moderate-intensity activity episodes to 10
      minutes or more could yield important health gains among older adults. However
      future studies will need to clarify whether attaining guideline amounts of PA in
      spells lasting 10 minutes or more is critical for reducing chronic disease risks
      as well as improving cardiometabolic risk factors.

PMID- 24745370
TI  - Diverse host feeding on nesting birds may limit early-season West Nile virus
      amplification.
AB  - Arboviral activity tracks vector availability, which in temperate regions means
      that transmission ceases during the winter and must be restarted each spring. In
      the northeastern United States, Culex restuans Theobald resumes its activity
      earlier than Culex pipiens L. and is thought to be important in restarting West
      Nile virus (WNV) transmission. Its role in WNV amplification, however, is
      unclear, because viral levels commonly remain low until the rise of Cx. pipiens
      later in the season. Because a vector's feeding habits can reveal key information
      about disease transmission, we identified early-season (April-June) blood meals
      from Cx. restuans collected throughout New Jersey, and compared them to published
      datasets from later in the season and also from other parts of the country. We
      found significantly higher avian diversity, including poor WNV hosts, and fewer
      blood meals derived from American Robins (17% versus over 40% found in later
      season). Critically, we identified blood meals from significantly more female
      than male birds in species where females are the incubating sex, suggesting that
      Cx. restuans is able to feed on such a wide variety of hosts in early spring
      because incubating birds are easy targets. Because WNV amplification depends on
      virus consistently reaching competent hosts, our results indicate that Cx.
      restuans is unlikely to be an amplifying vector of WNV in the early season. As
      the season progresses, however, changes in the availability of nesting birds may
      make it just as capable as Cx. pipiens, although at somewhat lower abundance as
      the summer progresses.

PMID- 24745371
TI  - Percutaneous nephrolithotomy for removal of encrusted ureteral stents: a
      multicenter study.
AB  - PURPOSE: Encrusted ureteral stents are a challenging endourologic problem. We
      performed a multi-institutional review of percutaneous nephrolithotomy (PCNL) as
      primary treatment for encrusted stents. MATERIALS AND METHODS: We identified 36
      patients who underwent PCNL for treatment of an encrusted stent. A retrospective
      review was performed to compile details of procedures and outcomes for these
      patients. RESULTS: In 36 patients, 38 renal units underwent PCNL for encrusted
      ureteral stents. The mean patient age was 47.1 years (+/-16.7), and the
      female:male ratio was 15:21. Mean stent indwelling time before removal was 28.2
      months (+/-27.8). The reason for long indwelling time was reported in 25 cases;
      these reasons included "patient unaware stent needed to be removed" (17 cases),
      pregnancy (2 cases), other comorbidities (3 cases), and patient incarceration (3
      cases). In 3 cases, the stent had become encrusted within 3 months of placement.
      Mean operative time was 162 minutes (+/-71). There were no major intraoperative
      complications, and no patients required blood transfusion. Litholapaxy was
      required for bladder coil encrustations in 22 cases (58%), and ureteroscopy with
      lithotripsy was required for encrustation of the ureteral portion of the stent in
      13 cases (34.2%). Second look percutaneous procedures were required in 13 cases
      (34.2%). The stent was removed at the time of PCNL without need for concomitant
      or delayed ureteroscopy and/or cystolitholapaxy in 8 cases (21%). Ultimately, all
      stents were removed successfully. Patients were rendered stone free according to
      radiographs in 24 cases (63%). CONCLUSIONS: In this multicenter review, PCNL is
      confirmed to be a safe and effective means of addressing the retained and
      encrusted ureteral stent. PCNL without ureteroscopy or litholapaxy was sufficient
      in a minority of cases (21%). Adjunctive endourologic modalities are often
      required, and the surgeon should anticipate the need for concomitant antegrade
      ureteroscopic laser lithotripsy and/or cystolitholapaxy. Although complete stent
      removal can be anticipated, residual fragments are not uncommon.

PMID- 24745372
TI  - The use of salt-inducible kinase inhibitors to treat autoimmune and inflammatory
      diseases: evaluation of WO2013136070.
AB  - Novel methods for the treatment of inflammatory and autoimmune diseases
      comprising the administration of salt-inducible kinase inhibitors are claimed.
      One novel inhibitor (HG-9-91-01) and the use of 2,4-diaminopyrimidine and 2,6
      diaminopyrimidine derivatives are claimed. The use of such inhibitors upregulates
      the level of the anti-inflammatory cytokine IL-10 in macrophages. 

PMID- 24745373
TI  - Effects of fertilizing with N, p, se, and zn on regulating the element and
      functional component contents and antioxidant activity of tea leaves planted in
      red soil.
AB  - New fertilizing strategies (with exogenetic N, P, Se, and Zn) were explored to
      regulate the element (Se, Zn, Mn, and Al) and functional component (polyphenol,
      catechins, free amino acid, polysaccharide, and caffeine) contents of new (a bud
      and two leaves, grown for about 10 days) and old tea leaves (grown for >3 months)
      cultivated in a hilly red soil region. Using four different fertilizing
      strategies (A, Se + Zn; B, Se + Zn + N; C, Se + Zn + P; D, Se + Zn + N + P), the
      Al and Mn contents of tea leaves in both new and old leaves were significantly
      decreased. Meanwhile, the contents of Se and Zn were increased, and the contents
      of some functional components as well as the antioxidant activities in tea leaves
      were improved. In particular, fertilizing strategy C showed the highest Se (0.444
      MUg/kg), total polyphenol (28.294%), and catechins (131.852 mg/g) contents and
      antioxidant activities (DPPH, 95.06%; FRAP, 3.81 mmol FeSO4/g; reducing power,
      1.26) as well as the lowest Al (222.005 mg/kg) content among these four
      strategies, whereas fertilizing strategy B showed the highest Zn (34.235 mg/kg),
      total free amino acid (5.60%), tea polysaccharide (5.79%), and caffeine (56.684
      mg/g) contents as well as the lowest Mn content (747.658 mg/kg). It has been
      proven that exogenetic elements (N, P, Se, and Zn) as fertilizers could be an
      effective way to produce tea leaves with higher Se, Zn, and functional component
      contents and antioxidant activity as well as lower Al and Mn contents in a red
      soil region. 

PMID- 24745374
TI  - The food environment of youth baseball.
AB  - BACKGROUND: Sports, such as youth baseball (YB), are popular outlets for
      increasing activity, yet there has been no investigation of food environments
      surrounding them. The aim of this study was to observe the types of foods
      available and consumed by players and spectators at YB events. METHODS: This was
      an observational assessment, by environmental scan, of foods consumed by players
      and family members at a YB field in northwest North Carolina. RESULTS:
      Participants included boys from six YB teams (n=51) between 8 and 11 years of age
      and families. A total of 12 YB games were observed. Most team snacks (72%)
      consisted of high-calorie food items, including French fries, candy, and cookies;
      most beverages (53%) consumed by players were sugar sweetened. We observed 313
      spectators and players, who consumed a total of 249 foods and 276 beverages. Most
      food and beverage items (89%) were purchased from the concession stand, of which
      73% were considered less-healthy options. CONCLUSIONS: High-calorie snacks and
      sugar-sweetened beverages dominate the YB environment. Despite the benefits of
      participating in sports, families of children participating in sports leagues may
      be increasing their risk for poor nutritional habits as a result of increased
      exposure to unhealthy foods and disruption of meal times.

PMID- 24745377
TI  - Insight into the binding mechanism of imipenem to human serum albumin by
      spectroscopic and computational approaches.
AB  - The mechanism of interaction between imipenem and HSA was investigated by various
      techniques like fluorescence, UV.vis absorbance, FRET, circular dichroism, urea
      denaturation, enzyme kinetics, ITC, and molecular docking. We found that imipenem
      binds to HSA at a high affinity site located in subdomain IIIA (Sudlow's site I)
      and a low affinity site located in subdomain IIA.IIB. Electrostatic interactions
      played a vital role along with hydrogen bonding and hydrophobic interactions in
      stabilizing the imipenem.HSA complex at subdomain IIIA, while only electrostatic
      and hydrophobic interactions were present at subdomain IIA.IIB. The binding and
      thermodynamic parameters obtained by ITC showed that the binding of imipenem to
      HSA was a spontaneous process (DeltaGD0(D)= -32.31 kJ mol(-1) for high affinity
      site and DeltaGD0(D) = -23.02 kJ mol(-1) for low affinity site) with binding
      constants in the range of 10(4)-10(5) M(-1). Spectroscopic investigation revealed
      only one binding site of imipenem on HSA (Ka~10(4) M(-1)). FRET analysis showed
      that the binding distance between imipenem and HSA (Trp-214) was optimal (r =
      4.32 nm) for quenching to occur. Decrease in esterase-like activity of HSA in the
      presence of imipenem showed that Arg-410 and Tyr-411 of subdomain IIIA (Sudlow's
      site II) were directly involved in the binding process. CD spectral analysis
      showed altered conformation of HSA upon imipenem binding. Moreover, the binding
      of imipenem to subdomain IIIA (Sudlow's site II) of HSA also affected its folding
      pathway as clear from urea-induced denaturation studies.

PMID- 24745376
TI  - DNA as a target for antimicrobials.
AB  - Resistance to antimicrobials is one of the biggest threats to our healthcare.
      However, in the last few decades very few truly novel antimicrobial compounds
      have been brought to market, creating the potential threat of a post-antibiotic
      era in which infections are very difficult to treat. Identification of novel
      compounds with antimicrobial activity is therefore paramount. Ideally, novel
      compounds should be designed that are active against targets that are not or
      barely used, as it is less likely that resistance already exists against such
      compounds. One example of an underexplored target in the treatment of infections
      is DNA. In this review we describe a number of DNA binding compounds and discuss
      potential opportunities and problems. 

PMID- 24745375
TI  - Chondrogenic phenotype of articular chondrocytes in monoculture and co-culture
      with mesenchymal stem cells in flow perfusion.
AB  - This work investigated the effect of flow perfusion bioreactor culture with and
      without transforming growth factor-beta3 (TGF-beta3) supplementation on the
      proliferation, extracellular matrix (ECM) production, and chondrogenic gene
      expression of chondrocytes both in monoculture and in co-culture with bone marrow
      derived mesenchymal stem cells (MSCs). Both cell populations were cultured on
      electrospun poly(E-caprolactone) scaffolds for 2 weeks in static or flow
      perfusion culture with and without TGF-beta3. Overall, it was observed that
      without growth factors, flow perfusion culture resulted in increased cell
      proliferation and ECM with a more cartilage-like composition. While with TGF
      beta3 induction, flow perfusion constructs generally had lower chondrogenic gene
      expression than the corresponding static cultures, the growth factor still had an
      inductive effect on the cells with enhanced gene expression compared with the
      corresponding noninduced cultures. In addition, while flow perfusion cultures
      generally had reduced overall ECM content, the ECM distribution was more
      homogenous compared with the corresponding static cultures. These results are
      significant in that they indicate that while flow perfusion culture has some
      beneficial effects on the chondrogenic phenotype of articular chondrocytes, flow
      perfusion alone is not sufficient to maintain the chondrogenic phenotype of
      chondrocytes in either monoculture or co-culture, thus demonstrating the
      advantages of using exogenously added growth factors in flow perfusion culture.
      Furthermore, the results demonstrate the advantages of flow perfusion culture for
      the creation of large tissue engineered constructs and the potential of co
      cultures of articular chondrocytes and MSCs to be used in flow perfusion culture.

PMID- 24745378
TI  - Delocalized currents without a ring of bonded atoms: strong delocalized electron
      currents induced by magnetic fields in noncyclic molecules.
AB  - Some noncyclic small molecules, electrically neutral or charged, sustain
      interatomic electronic currents in the presence of a stationary, spatially
      uniform magnetic field. The existence of fairly large delocalized electron flow
      is demonstrated in H2O, BH3, NH3, CH4, CH3-CH3, H3O+, CH3+, and NH4+, by plots of
      quantum mechanical current density. Convincing quantitative evidence is arrived
      at by current strengths, defined via a flux integral of the ab initio current
      density. Application of a simple ring current model shows that the delocalized
      current strengths account for the out-of-plane component of the magnetic
      shielding tensor along the symmetry axis. A definition of delocalized electron
      current as a current flowing along a closed loop containing three or more atoms
      is discussed.

PMID- 24745379
TI  - Anatomy and physiology of the aging neck.
AB  - This article discusses the surgically relevant anatomic and physiologic tenets of
      the aging neck. Procedures performed to rejuvenate and contour the aging neck can
      be challenging. A thorough understanding of the underlying neck anatomy, as well
      as the physiology associated with aging, is critical for surgical planning,
      execution, and achieving aesthetically pleasing outcomes. These topics are
      reviewed and used as the foundation for a discussion of various other techniques.

PMID- 24745380
TI  - Preoperative evaluation of the aging neck patient.
AB  - The appearance of the neck plays an important role in terms of the patient's
      overall facial appearance. Facial rejuvenation procedures incorporate
      rejuvenation and improvement of the neck's appearance as a key component.
      Preoperative evaluation of the aging neck determines the type of rejuvenation
      procedures that will be required. There are key components of the neck that
      should be evaluated, assessed, and documented. Subsequently, appropriate
      treatment modalities may be incorporated into the operative or treatment plan.
      Key components include evaluation of the mandibular margin, hyoid position,
      condition of the skin, soft tissue adipose, and the status of the platysmal
      muscle layer. 

PMID- 24745381
TI  - A progressive approach to neck rejuvenation.
AB  - The progressive approach to neck and facial rejuvenation is a comprehensive
      method for evaluation and correction of common aging changes seen in the lower
      face and neck. The surgical results are natural in appearance, as the
      rejuvenation method chosen is specifically and continuously adjusted for optimal
      results throughout the evaluation and surgical process. The increased burden on
      the surgeon to master a variety of techniques and to develop the judgment needed
      to decide in a progressive manner which is the most appropriate for use in each
      patient is more than compensated for by improved results and greater patient
      satisfaction. 

PMID- 24745382
TI  - Noninvasive treatment of the neck.
AB  - Emerging trends in neck rejuvenation include the incorporation of nonsurgical
      treatment modalities as an offering to those patients desiring minimal downtime
      and accepting of mild results. Intense focused ultrasound is a promising
      technology for treatment of the neck. It is rapidly growing in clinical use and
      undergoing further investigation to determine optimum treatment parameters and
      make its outcomes more predictable. 

PMID- 24745383
TI  - Neck skin rejuvenation.
AB  - The author of this article uses the pulsed ablative CO2 laser for resurfacing of
      the neck and face, based on the gold standard status of the CO2 laser and a novel
      post-treatment plan that greatly reduces adverse effects traditionally associated
      with fully ablative resurfacing. The croton oil peel is an inexpensive and
      effective modality for rejuvenating neck skin. The use of either technique as an
      adjunct to neck lift surgery, with or without facelift surgery, permits surgeons
      to fulfill the expectations of patients who want the skin of their face and neck
      to be homogeneous and more attractive. 

PMID- 24745384
TI  - Thermally confined micropulsed 1444-nm Nd:YAG interstitial fiber laser in the
      aging face and neck: an update.
AB  - This article provides an update on the contemporary use of the thermally confined
      micropulsed 1444-nm Nd:YAG interstitial fiber laser in the aging face and neck.
      Beginning with the concept that the use of Nd:YAG fiber lasers in aesthetic
      surgery is no longer limited to laser lipolysis, the article also covers the
      differentiating characteristics of the available Nd:YAG fiber laser wavelengths
      and laser tissue interaction and safety considerations when incorporating the use
      of these lasers into aging face surgery. 

PMID- 24745385
TI  - Adjunctive procedures to neck rejuvenation.
AB  - Rejuvenation of the neck often requires more than just a neck lift. Various steps
      and procedures exist to enhance the surgical technique or overall result. Fibrin
      sealants can be used to improve the recovery process and obviate the need for
      drain placement. Chin augmentation can be a critical part of creating a more
      refined neckline. Submandibular gland excision has been put forth as helpful to
      the overall aesthetic result. A low and anteriorly positioned hyoid bone creates
      an unattractive neckline that is difficult to treat. This article focuses on
      techniques beyond lifting and resurfacing that may enhance neck rejuvenation. 

PMID- 24745386
TI  - Techniques for rejuvenation of the neck platysma.
AB  - This article reviews evaluation and techniques for neck rejuvenation. It includes
      a detailed overview of cervical rhytidectomy and discusses the potential
      complications associated with surgical correction. A review of clinical outcomes
      in the literature is also included. 

PMID- 24745387
TI  - The extended SMAS approach to neck rejuvenation.
AB  - Jowling, submental lipoptosis, and platysmal banding can affect self-image and
      reduce quality of life, leading one to seek facial and neck rejuvenation. With
      realistic expectations, a facelift can provide the desired improvement in
      appearance and sense of well-being. Before any intervention, a detailed history,
      focused examination, communication of expected outcomes with the assistance of
      preoperative digital imaging, and discussion of perioperative instructions are of
      utmost importance. Although many techniques exist, the modified deep plane
      extended superficial muscular aponeurotic system rhytidectomy with submentoplasty
      reliably delivers a significant improvement with lasting results. 

PMID- 24745388
TI  - The deep-plane approach to neck rejuvenation.
AB  - This article provides the facial plastic surgeon with anatomic and embryologic
      evidence to support the use of the deep-plane rhytidectomy for optimal treatment
      of the aging neck. An anatomic basis is established that demonstrates this
      technique's ability to maximize neck rejuvenation through its direct relationship
      to midface soft-tissue mobilization. A detailed description of the procedure,
      aimed at providing safe and consistent results, is presented with insights into
      anatomic landmarks, technical nuances, and alternative approaches to facial
      variations. 

PMID- 24745389
TI  - Vertical neck lifting.
AB  - The authors' vertical neck lifting procedure is an extended deep plane facelift,
      which elevates the skin and SMAS-platysma complex as a composite unit. The goal
      is to redrape cervicomental laxity vertically onto the face rather than laterally
      and postauricularly. The authors consider this an extended technique because it
      lengthens the deep plane flap from the angle of the mandible into the neck to
      release the cervical retaining ligaments that limit platysmal redraping. This
      technique does not routinely use midline platysmal surgery because it counteracts
      the extent of vertical redraping. A majority of aging face patients are good
      candidates for this procedure in isolation, but indications for combining
      vertical neck lifting with submental surgery are elucidated.

PMID- 24745390
TI  - Complications/sequelae of neck rejuvenation.
AB  - Neck lift surgery performed in isolation or in conjunction with a facelift
      provides a more youthful cervicomental angle. Complications related to neck lift
      surgery vary from contour irregularities that may improve with time or
      conservative measures,to contour irregularities that persist and may benefit from
      delayed surgical intervention, to expanding hematomas that require immediate
      surgical intervention. This article reviews complications of neck lift surgery
      and their etiologies, methods to minimize the incidence of these complications,
      and management.

PMID- 24745391
TI  - Neck rejuvenation.

PMID- 24745392
TI  - Sudden onset of abdominal mass.

PMID- 24745393
TI  - Uhlmann phase as a topological measure for one-dimensional fermion systems.
AB  - We introduce the Uhlmann geometric phase as a tool to characterize symmetry
      protected topological phases in one-dimensional fermion systems, such as
      topological insulators and superconductors. Since this phase is formulated for
      general mixed quantum states, it provides a way to extend topological properties
      to finite temperature situations. We illustrate these ideas with some
      paradigmatic models and find that there exists a critical temperature Tc at which
      the Uhlmann phase goes discontinuously and abruptly to zero. This stands as a
      borderline between two different topological phases as a function of the
      temperature. Furthermore, at small temperatures we recover the usual notion of
      topological phase in fermion systems. 

PMID- 24745394
TI  - Likelihood-free methods for quantum parameter estimation.
AB  - In this Letter, we strengthen and extend the connection between simulation and
      estimation to exploit simulation routines that do not exactly compute the
      probability of experimental data, known as the likelihood function. Rather, we
      provide an explicit algorithm for estimating parameters of physical models given
      access to a simulator which is only capable of producing sample outcomes. Since
      our algorithm does not require that a simulator be able to efficiently compute
      exact probabilities, it is able to exponentially outperform standard algorithms
      based on exact computation. In this way, our algorithm opens the door for the
      application of new insights and resources to the problem of characterizing large
      quantum systems, which is exponentially intractable using standard simulation
      resources. 

PMID- 24745395
TI  - Pushing the limits of the eigenstate thermalization hypothesis towards mesoscopic
      quantum systems.
AB  - In the ongoing discussion on thermalization in closed quantum many-body systems,
      the eigenstate thermalization hypothesis has recently been proposed as a
      universal concept and has attracted considerable attention. So far this concept
      is, as the name states, hypothetical. The majority of attempts to overcome this
      hypothetical character are based on exact diagonalization, which implies for,
      e.g., spin systems a limitation of roughly 15 spins. In this Letter we present an
      approach that pushes this limit up to system sizes of roughly 35 spins, thereby
      going significantly beyond what is possible with exact diagonalization. A
      concrete application to a Heisenberg spin ladder which yields conclusive results
      is demonstrated. 

PMID- 24745396
TI  - Local PT symmetry violates the no-signaling principle.
AB  - Bender et al. [Phys. Rev. Lett. 80, 5243 (1998)] have developed PT-symmetric
      quantum theory as an extension of quantum theory to non-Hermitian Hamiltonians.
      We show that when this model has a local PT symmetry acting on composite systems,
      it violates the nonsignaling principle of relativity. Since the case of global PT
      symmetry is known to reduce to standard quantum mechanics A. Mostafazadeh [J.
      Math. Phys. 43, 205 (2001)], this shows that the PT-symmetric theory is either a
      trivial extension or likely false as a fundamental theory.

PMID- 24745397
TI  - Reference-frame-independent quantum-key-distribution server with a telecom tether
      for an on-chip client.
AB  - We demonstrate a client-server quantum key distribution (QKD) scheme. Large
      resources such as laser and detectors are situated at the server side, which is
      accessible via telecom fiber to a client requiring only an on-chip polarization
      rotator, which may be integrated into a handheld device. The detrimental effects
      of unstable fiber birefringence are overcome by employing the reference-frame
      independent QKD protocol for polarization qubits in polarization maintaining
      fiber, where standard QKD protocols fail, as we show for comparison. This opens
      the way for quantum enhanced secure communications between companies and members
      of the general public equipped with handheld mobile devices, via telecom-fiber
      tethering. 

PMID- 24745398
TI  - Hardness of classically simulating the one-clean-qubit model.
AB  - Deterministic quantum computation with one quantum bit (DQC1) [E. Knill and R.
      Laflamme, Phys. Rev. Lett. 81, 5672 (1998)] is a model of quantum computing where
      the input is restricted to containing a single qubit in a pure state and has all
      other qubits in a completely mixed state. Only the single pure qubit is measured
      at the end of the computation. While it is known that DQC1 can efficiently solve
      several problems for which no known classical efficient algorithms exist, the
      question of whether DQC1 is really more powerful than classical computation
      remains open. In this Letter, we introduce a slightly modified version of DQC1,
      which we call DQC1(k), where k output qubits are measured, and show that DQC1(k)
      cannot be classically efficiently simulated for any k>=3 unless the polynomial
      hierarchy collapses at the third level.

PMID- 24745399
TI  - Most efficient quantum thermoelectric at finite power output.
AB  - Machines are only Carnot efficient if they are reversible, but then their power
      output is vanishingly small. Here we ask, what is the maximum efficiency of an
      irreversible device with finite power output? We use a nonlinear scattering
      theory to answer this question for thermoelectric quantum systems, heat engines
      or refrigerators consisting of nanostructures or molecules that exhibit a Peltier
      effect. We find that quantum mechanics places an upper bound on both power output
      and on the efficiency at any finite power. The upper bound on efficiency equals
      Carnot efficiency at zero power output but decays with increasing power output.
      It is intrinsically quantum (wavelength dependent), unlike Carnot efficiency.
      This maximum efficiency occurs when the system lets through all particles in a
      certain energy window, but none at other energies. A physical implementation of
      this is discussed, as is the suppression of efficiency by a phonon heat flow. 

PMID- 24745401
TI  - Proposal for axion dark matter detection using an LC circuit.
AB  - We show that dark matter axions cause an oscillating electric current to flow
      along magnetic field lines. The oscillating current induced in a strong magnetic
      field B0 produces a small magnetic field Ba. We propose to amplify and detect Ba
      using a cooled LC circuit and a very sensitive magnetometer. This appears to be a
      suitable approach to searching for axion dark matter in the 10(-7) to 10(-9)  eV
      mass range.

PMID- 24745403
TI  - Magic square from Yang-Mills squared.
AB  - We give a unified description of D=3 super-Yang-Mills theory with N=1, 2, 4, and
      8 supersymmeties in terms of the four division algebras: reals (R), complexes
      (C), quaternions (H) and octonions (O). Tensoring left and right super-Yang-Mills
      multiplets with N=1, 2, 4, 8 we obtain a magic square RR, CR, CC, HR, HC, HH, OR,
      OC, OH, OO description of D=3 supergravity with N=2, 3, 4, 5, 6, 8, 9, 10, 12,
      16. 

PMID- 24745404
TI  - Dynamical R-parity violation.
AB  - We present a new paradigm for supersymmetric theories with R-parity violation
      (RPV). At high scale, R parity is conserved in the visible sector but
      spontaneously broken in the supersymmetry-breaking sector. The breaking is then
      dynamically mediated to the visible sector and is manifested via
      nonrenormalizable operators at low energy. Consequently, RPV operators originate
      from the Kahler potential rather than the superpotential, and are naturally
      suppressed by the supersymmetry-breaking scale, explaining their small
      magnitudes. A new set of nonholomorphic RPV operators is identified and found to
      often dominate over the standard RPV ones. We study the relevant low-energy
      constraints arising from baryon-number violating processes, proton decay, and
      flavor changing neutral currents, which may all be satisfied if a solution to the
      standard model flavor puzzle is incorporated. The chiral structure of the RPV
      operators implies new and distinct collider signatures, indicating the need to
      alter current techniques in searching for RPV at the LHC. 

PMID- 24745402
TI  - Evidence for gravitational lensing of the cosmic microwave background
      polarization from cross-correlation with the cosmic infrared background.
AB  - We reconstruct the gravitational lensing convergence signal from cosmic microwave
      background (CMB) polarization data taken by the Polarbear experiment and cross
      correlate it with cosmic infrared background maps from the Herschel satellite.
      From the cross spectra, we obtain evidence for gravitational lensing of the CMB
      polarization at a statistical significance of 4.0sigma and indication of the
      presence of a lensing B-mode signal at a significance of 2.3sigma. We demonstrate
      that our results are not biased by instrumental and astrophysical systematic
      errors by performing null tests, checks with simulated and real data, and
      analytical calculations. This measurement of polarization lensing, made via the
      robust cross-correlation channel, not only reinforces POLARBEAR auto-correlation
      measurements, but also represents one of the early steps towards establishing CMB
      polarization lensing as a powerful new probe of cosmology and astrophysics. 

PMID- 24745406
TI  - Search for dinucleon decay into kaons in Super-Kamiokande.
AB  - A search for the dinucleon decay pp -> K+ K+ has been performed using 91.6 
      kton.yr data from Super-Kamiokande-I. This decay provides a sensitive probe of
      the R-parity-violating parameter lambda112''. A boosted decision tree analysis
      found no signal candidates in the data. The expected background was 0.28+/-0.19
      atmospheric neutrino induced events and the estimated signal detection efficiency
      was 12.6%+/-3.2%. A lower limit of 1.7*10(32)  years has been placed on the
      partial lifetime of the decay O16 -> C14K+ K+ at 90% C.L. A corresponding upper
      limit of 7.8*10(-9) has been placed on the parameter lambda112''.

PMID- 24745408
TI  - 1p3/2 proton-hole state in 132Sn and the shell structure along N = 82.
AB  - A low-lying state in 131In82, the one-proton hole nucleus with respect to double
      magic 132Sn, was observed by its gamma decay to the Ipi=1/2- beta-emitting
      isomer. We identify the new state at an excitation energy of Ex=1353  keV, which
      was populated both in the beta decay of 131Cd83 and after beta-delayed neutron
      emission from 132Cd84, as the previously unknown pip3/2 single-hole state with
      respect to the 132Sn core. Exploiting this crucial new experimental information,
      shell-model calculations were performed to study the structure of experimentally
      inaccessible N=82 isotones below 132Sn. The results evidence a surprising absence
      of proton subshell closures along the chain of N=82 isotones. The consequences of
      this finding for the evolution of the N=82 shell gap along the r-process path are
      discussed.

PMID- 24745409
TI  - First observation of the unbound nucleus 15Ne.
AB  - We report on the first observation of the unbound proton-rich nucleus 15Ne. Its
      ground state and first excited state were populated in two-neutron knockout
      reactions from a beam of 500 MeV/u 17Ne. The 15Ne ground state is found to be
      unbound by 2.522(66) MeV. The decay proceeds directly to 13O with simultaneous
      two-proton emission. No evidence for sequential decay via the energetically
      allowed 2- and 1- states in 14F is observed. The 15Ne ground state is shown to
      have a strong configuration with two protons in the (sd) shell around 13O with a
      63(5)% (1s1/2)2 component.

PMID- 24745412
TI  - Range-separated Brueckner coupled cluster doubles theory.
AB  - We introduce a range-separation approximation to coupled cluster doubles (CCD)
      theory that successfully overcomes limitations of regular CCD when applied to the
      uniform electron gas. We combine the short-range ladder channel with the long
      range ring channel in the presence of a Bruckner renormalized one-body
      interaction and obtain ground-state energies with an accuracy of 0.001
      a.u./electron across a wide range of density regimes. Our scheme is particularly
      useful in the low-density and strongly correlated regimes, where regular CCD has
      serious drawbacks. Moreover, we cure the infamous overcorrelation of approaches
      based on ring diagrams (i.e., the particle-hole random phase approximation). Our
      energies are further shown to have appropriate basis set and thermodynamic limit
      convergence, and overall this scheme promises energetic properties for realistic
      periodic and extended systems which existing methods do not possess. 

PMID- 24745411
TI  - Nonequilibrium phase transition with gravitational-like interaction in a cloud of
      cold atoms.
AB  - We propose to use a cloud of laser-cooled atoms in a quasi-two-dimensional trap
      to investigate a nonequilibrium collapse phase transition in the presence of a
      gravitational-like interaction. Using theoretical arguments and numerical
      simulations, we show that, like in two-dimensional gravity, a transition to a
      collapsed state occurs below a critical temperature. In addition and as a
      signature of the nonequilibrium nature of the system, persistent particle
      currents, dramatically increasing close to the phase transition, are observed. 

PMID- 24745410
TI  - JLab measurement of the 4He charge form factor at large momentum transfers.
AB  - The charge form factor of 4He has been extracted in the range 29  fm(-2) <= Q2 <=
      77  fm(-2) from elastic electron scattering, detecting 4He recoil nuclei and
      electrons in coincidence with the high resolution spectrometers of the Hall A
      Facility of Jefferson Lab. The measurements have uncovered a second diffraction
      minimum for the form factor, which was predicted in the Q2 range of this
      experiment. The data are in qualitative agreement with theoretical calculations
      based on realistic interactions and accurate methods to solve the few-body
      problem.

PMID- 24745413
TI  - Recollision scenario without tunneling: role of the ionic core potential.
AB  - We present a purely classical recollision scenario, i.e., without tunneling,
      which, in contrast to the standard three-step model, takes into account the ionic
      core potential fully at all stages of the recollision process and is valid at all
      intensities. We find that a key periodic orbit drives the recollisions by guiding
      electrons away and back to the core. At sufficiently high intensity, we connect
      our scenario to the three-step model, and explain why the three-step model leads
      to good agreement with the cutoff in high harmonic generation despite neglecting
      the core potential after tunneling. 

PMID- 24745414
TI  - Enhanced up-conversion of entangled photons and quantum interference under a
      localized field in nanostructures.
AB  - We theoretically investigate the up-conversion process of two entangled photons
      on a molecule, which is coupled by a cavity or nanoscale metallic structure.
      Within one-dimensional input-output theory, the propagators of the photons are
      derived analytically and the up-conversion probability is calculated numerically.
      It is shown that the coupling with the nanostructure clearly enhances the
      process. We also find that the enhancement becomes further pronounced for some
      balanced system parameters, such as the quantum correlation between photons,
      radiation decay, and coupling between the nanostructure and molecule. The
      nonmonotonic dependencies are reasonably explained in view of quantum
      interference between the coupled modes of the whole system. This result indicates
      that controlling quantum interference and correlation is crucial for few-photon
      nonlinearity, and provides a new guidance to wide variety of fields, e.g.,
      quantum electronics and photochemistry. 

PMID- 24745415
TI  - Orthogonal spectral coding of entangled photons.
AB  - We extend orthogonal optical coding, previously applied to multiuser classical
      communication networks, to entangled photons. Using a pulse shaper and sum
      frequency generation for ultrafast coincidence detection, we demonstrate encoding
      and decoding of biphoton wave packets. Applying one code to the signal photon
      spreads the wave packet in time and creates a null at zero delay; filtering the
      idler with the matched code recovers a narrow correlation peak, whereas applying
      any other code leaves the wave packet spread. Our results could prove useful in
      the development of code-based quantum communication networks. 

PMID- 24745416
TI  - Parametric amplification of the mechanical vibrations of a suspended nanowire by
      magnetic coupling to a Bose-Einstein condensate.
AB  - We show how the vibrational modes of a nanowire may be coherently manipulated
      with a Bose-Einstein condensate of ultracold atoms. We consider the
      magnetomechanical coupling between paramagnetic atoms and a suspended nanowire
      carrying a dc current. Atomic spin flips produce a backaction onto the wire
      vibrations, which can lead to mechanical mode amplification. In contrast to
      systems considered before, the condensate has a finite energy bandwidth in the
      range of the chemical potential and we explore the consequences of this on the
      parametric drive. Applying the resolvent method, we determine the threshold
      coupling and we also find a significant frequency shift of the vibration due to
      magnetomechanical dressing. 

PMID- 24745417
TI  - Reconfigurable long-range phonon dynamics in optomechanical arrays.
AB  - We investigate periodic optomechanical arrays as reconfigurable platforms for
      engineering the coupling between multiple mechanical and electromagnetic modes
      and for exploring many-body phonon dynamics. Exploiting structural resonances in
      the coupling between light fields and collective motional modes of the array, we
      show that tunable effective long-range interactions between mechanical modes can
      be achieved. This paves the way towards the implementation of controlled phononic
      walks and heat transfer on densely connected graphs as well as the coherent
      transfer of excitations between distant elements of optomechanical arrays. 

PMID- 24745418
TI  - Coherently opening a high-Q cavity.
AB  - We propose a general framework to effectively "open" a high-Q resonator, that is,
      to release the quantum state initially prepared in it in the form of a traveling
      electromagnetic wave. This is achieved by employing a mediating mode that
      scatters coherently the radiation from the resonator into a one-dimensional
      continuum of modes such as a waveguide. The same mechanism may be used to "feed"
      a desired quantum field to an initially empty cavity. Switching between an open
      and "closed" resonator may then be obtained by controlling either the detuning of
      the scatterer or the amount of time it spends in the resonator. First, we
      introduce the model in its general form, identifying (i) the traveling mode that
      optimally retains the full quantum information of the resonator field and (ii) a
      suitable figure of merit that we study analytically in terms of the system
      parameters. Then, we discuss two feasible implementations based on ensembles of
      two-level atoms interacting with cavity fields. In addition, we discuss how to
      integrate traditional cavity QED in our proposal using three-level atoms. 

PMID- 24745419
TI  - Two-photon dynamics in coherent Rydberg atomic ensemble.
AB  - We study the interaction of two photons in a Rydberg atomic ensemble under the
      condition of electromagnetically induced transparency, combining a semiclassical
      approach for pulse propagation and a complete quantum treatment for quantum state
      evolution. We find that the blockade regime is not suitable for implementing
      photon-photon cross-phase modulation due to pulse absorption and dispersion.
      However, approximately ideal cross-phase modulation can be realized based on
      relatively weak interactions, with counterpropagating and transversely separated
      pulses. 

PMID- 24745420
TI  - Experiments on seismic metamaterials: molding surface waves.
AB  - Materials engineered at the micro- and nanometer scales have had a tremendous and
      lasting impact in photonics and phononics. At much larger scales, natural soils
      civil engineered at decimeter to meter scales may interact with seismic waves
      when the global properties of the medium are modified, or alternatively thanks to
      a seismic metamaterial constituted of a mesh of vertical empty inclusions bored
      in the initial soil. Here, we show the experimental results of a seismic test
      carried out using seismic waves generated by a monochromatic vibrocompaction
      probe. Measurements of the particles' velocities show a modification of the
      seismic energy distribution in the presence of the metamaterial in agreement with
      numerical simulations using an approximate plate model. For complex natural
      materials such as soils, this large-scale experiment was needed to show the
      practical feasibility of seismic metamaterials and to stress their importance for
      applications in civil engineering. We anticipate this experiment to be a starting
      point for smart devices for anthropic and natural vibrations. 

PMID- 24745421
TI  - Anomalous and quantum Hall effects in lossy photonic lattices.
AB  - We theoretically discuss analogues of the anomalous and the integer quantum Hall
      effect in driven-dissipative two-dimensional photonic lattices in the presence of
      a synthetic gauge field. Photons are coherently injected by a spatially localized
      pump, and the transverse shift of the in-plane light distribution under the
      effect of an additional uniform force is considered. Depending on pumping
      parameters, the transverse shift turns out to be proportional either to the
      global Chern number (integer quantum Hall effect) or to the local Berry curvature
      (anomalous Hall effect). This suggests a viable route to experimentally measure
      these quantities in photonic lattices. 

PMID- 24745422
TI  - Coherent control of total transmission of light through disordered media.
AB  - We demonstrate order of magnitude coherent control of total transmission of light
      through random media by shaping the wave front of the input light. To understand
      how the finite illumination area on a wide slab affects the maximum values of
      total transmission, we develop a model based on random matrix theory that reveals
      the role of long-range correlations. Its predictions are confirmed by numerical
      simulations and provide physical insight into the experimental results. 

PMID- 24745423
TI  - Quantum-limited amplification via reservoir engineering.
AB  - We describe a new kind of phase-preserving quantum amplifier which utilizes
      dissipative interactions in a parametrically coupled three-mode bosonic system.
      The use of dissipative interactions provides a fundamental advantage over
      standard cavity-based parametric amplifiers: large photon number gains are
      possible with quantum-limited added noise, with no limitation on the gain
      bandwidth product. We show that the scheme is simple enough to be implemented
      both in optomechanical systems and in superconducting microwave circuits. 

PMID- 24745424
TI  - Boundary-induced instabilities in coupled oscillators.
AB  - A novel class of nonequilibrium phase transitions at zero temperature is found in
      chains of nonlinear oscillators. For two paradigmatic systems, the Hamiltonian XY
      model and the discrete nonlinear Schrodinger equation, we find that the
      application of boundary forces induces two synchronized phases, separated by a
      nontrivial interfacial region where the kinetic temperature is finite. Dynamics
      in such a supercritical state displays anomalous chaotic properties whereby some
      observables are nonextensive and transport is superdiffusive. At finite
      temperatures, the transition is smoothed, but the temperature profile is still
      nonmonotonic. 

PMID- 24745425
TI  - Spatiotemporal oscillation patterns in the collective relaxation dynamics of
      interacting particles in periodic potentials.
AB  - We demonstrate the emergence of self-organized structures in the course of the
      relaxation of an initially excited, dissipative, and finite chain of interacting
      particles in a periodic potential towards its many particle equilibrium
      configuration. Specifically, we observe a transition from an in phase correlated
      motion via phase randomized oscillations towards oscillations with a phase
      difference pi between adjacent particles thereby yielding the growth of long time
      transient spatiotemporal oscillation patterns. Parameter modifications allow for
      designing these patterns, including steady states and even states that combine in
      phase and correlated out of phase oscillations along the chain. The complex
      relaxation dynamics is based on finite size effects together with an evolution
      running from the nonlinear to the linear regime, thereby providing a highly
      unbalanced population of the center-of-mass and relative motion. 

PMID- 24745407
TI  - Observation of a charged charmoniumlike structure in e+ e- -> (D* D*)+/- pi? at
      ?s = 4.26  GeV.
AB  - We study the process e+ e- ->(D* D*)+/- pi? at a center-of-mass energy of 4.26
      GeV using a 827  pb(-1) data sample obtained with the BESIII detector at the
      Beijing Electron Positron Collider. Based on a partial reconstruction technique,
      the Born cross section is measured to be (137+/-9+/-15)  pb. We observe a
      structure near the (D* D*)+/- threshold in the pi? recoil mass spectrum, which we
      denote as the Zc+/-(4025). The measured mass and width of the structure are
      (4026.3+/-2.6+/-3.7)  MeV/c2 and (24.8+/-5.6+/-7.7)  MeV, respectively. Its
      production ratio sigma(e+ e- -> Zc+/-(4025)pi? -> (D* D*)+/- pi?)/sigma(e+ e- ->
      (D* D*)+/- pi?) is determined to be 0.65+/-0.09+/-0.06. The first uncertainties
      are statistical and the second are systematic.

PMID- 24745426
TI  - Lift-off instability during the impact of a drop on a solid surface.
AB  - We directly measure the rapid spreading dynamics succeeding the impact of a
      droplet of fluid on a solid, dry surface. Upon impact, the air separating the
      liquid from the solid surface fails to drain and wetting is delayed as the liquid
      rapidly spreads outwards over a nanometer thin film of air. We show that the
      approach of the spreading liquid front toward the surface is unstable and the
      spreading front lifts off away from the surface. Lift-off ensues well before the
      liquid contacts the surface, in contrast with prevailing paradigm where lift-off
      of the liquid is contingent on solid-liquid contact and the formation of a
      viscous boundary layer. Here we investigate the dynamics of liquid spreading over
      a thin film of air and its lift-off away from the surface over a large range of
      fluid viscosities and find that the lift-off instability is dependent on
      viscosity and occurs at a time that scales with the viscosity to the power of one
      half. 

PMID- 24745427
TI  - Inverse problem of capillary filling.
AB  - The inverse problem of capillary filling, as defined in this work, consists in
      determining the capillary radius profile from experimental data of the meniscus
      position l as a function of time t. This problem is central in diverse
      applications, such as the characterization of nanopore arrays or the design of
      passive transport in microfluidics; it is mathematically ill posed and has
      multiple solutions; i.e., capillaries with different geometries may produce the
      same imbibition kinematics. Here a suitable approach is proposed to solve this
      problem, which is based on measuring the imbibition kinematics in both tube
      directions. Capillary filling experiments to validate the calculation were made
      in a wide range of length scales: glass capillaries with a radius of around 150 
      MUm and anodized alumina membranes with a pores radius of around 30  nm were
      used. The proposed method was successful in identifying the radius profile in
      both systems. Fundamental aspects also emerge in this study, notably the fact
      that the l(t)?t1/2 kinematics (Lucas-Washburn relation) is not exclusive of
      uniform cross-sectional capillaries. 

PMID- 24745428
TI  - Interaction of relativistic electron-vortex beams with few-cycle laser pulses.
AB  - We study the interaction of relativistic electron-vortex beams (EVBs) with laser
      light. Exact analytical solutions for this problem are obtained by employing the
      Dirac-Volkov wave functions to describe the (monoenergetic) distribution of the
      electrons in vortex beams with well-defined orbital angular momentum. Our new
      solutions explicitly show that the orbital angular momentum components of the
      laser field couple to the total angular momentum of the electrons. When the field
      is switched off, it is shown that the laser-driven EVB coincides with the field
      free EVB as reported by Bliokh et al. [Phys. Rev. Lett. 107, 174802 (2011)].
      Moreover, we calculate the probability density for finding an electron in the
      beam profile and demonstrate that the center of the beam is shifted with respect
      to the center of the field-free EVB.

PMID- 24745429
TI  - Microbunching instability suppression via electron-magnetic-phase mixing.
AB  - Control of the microbunching instability is a fundamental requirement in modern
      high-brightness electron linacs, in order to prevent misleading responses of beam
      optical diagnostics and contamination in the generation of coherent radiation,
      such as free electron lasers. We present the first experimental demonstration of
      control and suppression of microbunching instability by means of particles'
      longitudinal phase mixing in a magnetic chicane. In the presence of phase mixing,
      the intensity of the beam-emitted optical transition radiation, which is used as
      an indicator of the instability gain at optical wavelengths, is reduced by one
      order of magnitude and brought to the same level provided, alternatively, by beam
      heating. The experimental results are in agreement with particle tracking and
      analytical evaluations of the instability gain. This article is extended to a
      discussion of applications of magnetic-phase mixing to the generation of
      quasicold high-brightness ultrarelativistic electron beams. 

PMID- 24745430
TI  - Quasi-phase-matched laser wakefield acceleration.
AB  - The energy gain in laser wakefield acceleration is ultimately limited by
      dephasing, occurring when accelerated electrons outrun the accelerating phase of
      the wakefield. We apply quasi-phase-matching, enabled by axially modulated plasma
      channels, to overcome this limitation. Theory and simulations are presented
      showing that weakly relativistic laser intensities can drive significant electron
      energy gains. 

PMID- 24745431
TI  - First observations of nonhydrodynamic mix at the fuel-shell interface in shock
      driven inertial confinement implosions.
AB  - A strong nonhydrodynamic mechanism generating atomic fuel-shell mix has been
      observed in strongly shocked inertial confinement fusion implosions of thin
      deuterated-plastic shells filled with 3He gas. These implosions were found to
      produce D3He-proton shock yields comparable to implosions of identical shells
      filled with a hydroequivalent 50?50 D3He gas mixture. Standard hydrodynamic
      mixing cannot explain this observation, as hydrodynamic modeling including mix
      predicts a yield an order of magnitude lower than was observed. Instead, these
      results can be attributed to ion diffusive mix at the fuel-shell interface.

PMID- 24745432
TI  - Electrothermal instability mitigation by using thick dielectric coatings on
      magnetically imploded conductors.
AB  - Recent experiments on Sandia's Z facility have confirmed simulation predictions
      of dramatically reduced instability growth in solid metallic rods when thick
      dielectric coatings are used to mitigate density perturbations arising from an
      electrothermal instability. These results provide further evidence that the
      inherent surface roughness as a result of target fabrication is not the dominant
      seed for the growth of magneto-Rayleigh-Taylor instabilities in liners with
      carefully machined smooth surfaces, but rather electrothermal instabilities that
      form early in the electrical current pulse as Joule heating melts and vaporizes
      the liner surface. These results suggest a new technique for substantially
      reducing the integral magneto-Rayleigh-Taylor instability growth in magnetically
      driven implosions, such as cylindrical dynamic material experiments and inertial
      confinement fusion concepts. 

PMID- 24745433
TI  - Spin waves and dielectric softening of polar molecule condensates.
AB  - We consider an oblate Bose-Einstein condensate of heteronuclear polar molecules
      in a weak applied electric field. This system supports a rich quasiparticle
      spectrum that plays a critical role in determining its bulk dielectric
      properties. In particular, in sufficiently weak fields the system undergoes a
      polarization wave rotonization, leading to the development of textured electronic
      structure and a dielectric instability that is characteristic of the onset of a
      negative static dielectric function. 

PMID- 24745405
TI  - Search for Majorana neutrinos in B- -> pi+ MU- MU- decays.
AB  - A search for heavy Majorana neutrinos produced in the B- -> pi+ MU- MU- decay
      mode is performed using 3  fb(-1) of integrated luminosity collected with the
      LHCb detector in pp collisions at center-of-mass energies of 7 and 8 TeV at the
      LHC. Neutrinos with masses in the range 250 to 5000 MeV and lifetimes from zero
      to 1000 ps are probed. In the absence of a signal, upper limits are set on the
      branching fraction B(B- -> pi+ MU- MU-) as functions of neutrino mass and
      lifetime. These limits are on the order of 10(-9) for short neutrino lifetimes of
      1 ps or less. Limits are also set on the coupling between the muon and a possible
      fourth-generation neutrino.

PMID- 24745434
TI  - Universal equation of state and pseudogap in the two-dimensional Fermi gas.
AB  - We determine the thermodynamic properties and the spectral function for a
      homogeneous two-dimensional Fermi gas in the normal state using the Luttinger
      Ward, or self-consistent T-matrix, approach. The density equation of state
      deviates strongly from that of the ideal Fermi gas even for moderate
      interactions, and our calculations suggest that temperature has a pronounced
      effect on the pressure in the crossover from weak to strong coupling, consistent
      with recent experiments. We also compute the superfluid transition temperature
      for a finite system in the crossover region. There is a pronounced pseudogap
      regime above the transition temperature: the spectral function shows a Bogoliubov
      like dispersion with backbending, and the density of states is significantly
      suppressed near the chemical potential. The contact density at low temperatures
      increases with interaction and compares well with both experiment and zero
      temperature Monte Carlo results. 

PMID- 24745435
TI  - Low temperature heat capacity of a severely deformed metallic glass.
AB  - The low temperature heat capacity of amorphous materials reveals a low-frequency
      enhancement (boson peak) of the vibrational density of states, as compared with
      the Debye law. By measuring the low-temperature heat capacity of a Zr-based bulk
      metallic glass relative to a crystalline reference state, we show that the heat
      capacity of the glass is strongly enhanced after severe plastic deformation by
      high-pressure torsion, while subsequent thermal annealing at elevated
      temperatures leads to a significant reduction. The detailed analysis of
      corresponding molecular dynamics simulations of an amorphous Zr-Cu glass shows
      that the change in heat capacity is primarily due to enhanced low-frequency modes
      within the shear band region. 

PMID- 24745436
TI  - Polarization-controlled circular second-harmonic generation from metal hole
      arrays with threefold rotational symmetry.
AB  - The discrete rotational symmetry of nanostructures provides a powerful and simple
      guiding principle for designing the second-harmonic generation process in
      nonlinear metamaterials. We demonstrate that, in achiral nanostructures with
      threefold rotational symmetries, a circularly polarized fundamental beam produces
      a countercircularly polarized second-harmonic beam. In this case, the
      polarization state of the second harmonic is determined in a very simple manner.
      We also demonstrate how rotational symmetries in nonlinear metamaterials manifest
      themselves in SHG selection rules. 

PMID- 24745437
TI  - Steering of a sub-GeV electron beam through planar channeling enhanced by
      rechanneling.
AB  - We report the observation of efficient steering of a 855 MeV electron beam at
      MAMI (MAinzer MIkrotron) facilities by means of planar channeling and volume
      reflection in a bent silicon crystal. A 30.5  MUm thick plate of (211) oriented
      Si was bent to cause quasimosaic deformation of the (111) crystallographic
      planes, which were used for coherent interaction with the electron beam. The
      experimental results are analogous to those recorded some years ago at energy
      higher than 100 GeV, which is the only comparable study to date. Monte Carlo
      simulations demonstrated that rechanneling plays a considerable role in a
      particle's dynamics and hinders the spoiling of channeled particles. These
      results allow a better understanding of the dynamics of electrons subject to
      coherent interactions in a bent silicon crystal in the sub-GeV energy range,
      which is relevant for realization of innovative x-ray sources based on channeling
      in periodically bent crystals. 

PMID- 24745438
TI  - Exploring the limit of dislocation based plasticity in nanostructured metals.
AB  - A twofold decrease to an unexplored scale of 5 nm was produced in Cu by applying
      a large sliding load in liquid nitrogen. Statistical and universal scaling
      analyses of deformation induced high angle boundaries, dislocation boundaries,
      and individual dislocations observed by high resolution electron microscopy
      reveal that dislocation processes still dominate. Dislocation based plasticity
      continues far below the transition suggested by experiment and molecular dynamics
      simulations, with a limit below 5 nm. Very high strength metals may emerge based
      on this enhanced structural refinement. 

PMID- 24745439
TI  - Behavior of the Widom line in critical phenomena.
AB  - Using linear scaling theory, we study the behavior of response functions extrema
      in the vicinity of the critical point. We investigate how the speed of
      convergence of the loci of response function extrema to the Widom line depends on
      the parameters of the linear scaling theory. We find that when the slope of the
      coexistence line is near zero, the line of specific heat maxima does not follow
      the Widom line but instead follows the coexistence line. This has relevance for
      the detection of liquid-liquid critical points, which can exhibit a near
      horizontal coexistence line. Our theoretical predictions are confirmed by
      computer simulations of a family of spherically symmetric potentials. 

PMID- 24745440
TI  - Impact of plastic deformation and shear band formation on the boson heat capacity
      peak of a bulk metallic glass.
AB  - The effect of annealing on the low-temperature heat capacity of a bulk
      Pd38.5Ni40P21.5 metallic glass is investigated for as-quenched and deformed
      (rolled) states. Although the boson heat capacity peak increases with increasing
      strain, it relaxes faster and to a lower level compared to that of the as
      quenched state after annealing treatments both below and above the glass
      transition temperature Tg. The glass is found to retain a certain "memory" on the
      room-temperature plastic deformation even after annealing above Tg. Indications
      for two counteracting processes that might be related to different types of shear
      bands are observed. 

PMID- 24745400
TI  - Constraints on cosmic strings from the LIGO-Virgo gravitational-wave detectors.
AB  - Cosmic strings can give rise to a large variety of interesting astrophysical
      phenomena. Among them, powerful bursts of gravitational waves (GWs) produced by
      cusps are a promising observational signature. In this Letter we present a search
      for GWs from cosmic string cusps in data collected by the LIGO and Virgo
      gravitational wave detectors between 2005 and 2010, with over 625 days of live
      time. We find no evidence of GW signals from cosmic strings. From this result, we
      derive new constraints on cosmic string parameters, which complement and improve
      existing limits from previous searches for a stochastic background of GWs from
      cosmic microwave background measurements and pulsar timing data. In particular,
      if the size of loops is given by the gravitational backreaction scale, we place
      upper limits on the string tension GMU below 10(-8) in some regions of the cosmic
      string parameter space.

PMID- 24745441
TI  - Continuous self-energy of ions at the dielectric interface.
AB  - By treating both the short-range (solvation) and long-range (image force)
      electrostatic forces as well as charge polarization induced by these forces in a
      consistent manner, we obtain a simple theory for the self-energy of an ion that
      is continuous across the interface. Along with nonelectrostatic contributions,
      our theory enables a unified description of ions on both sides of the interface.
      Using intrinsic parameters of the ions, we predict the specific ion effect on the
      interfacial affinity of halogen anions at the water-air interface, and the strong
      adsorption of hydrophobic ions at the water-oil interface, in agreement with
      experiments and atomistic simulations. 

PMID- 24745442
TI  - Emergence of a coherent in-gap state in the SmB6 Kondo insulator revealed by
      scanning tunneling spectroscopy.
AB  - We use scanning tunneling microscopy to investigate the (001) surface of a
      cleaved SmB6 Kondo insulator. Variable temperature dI/dV spectroscopy up to 60 K
      reveals a gaplike density of state suppression around the Fermi level, which is
      due to the hybridization between the itinerant Sm 5d band and localized Sm 4f
      band. At temperatures below 40 K, a sharp coherence peak emerges within the
      hybridization gap near the lower gap edge. We propose that the in-gap resonance
      state is due to a collective excitation in magnetic origin with the presence of
      spin-orbital coupling and mixed valence fluctuations. These results shed new
      light on the electronic structure evolution and transport anomaly in SmB6. 

PMID- 24745443
TI  - Anisotropic Weyl fermions from the quasiparticle excitation spectrum of a 3D
      Fulde-Ferrell superfluid.
AB  - Weyl fermions, first proposed for describing massless chiral Dirac fermions in
      particle physics, have not been observed yet in experiments. Recently, much
      effort has been devoted to explore Weyl fermions around band touching points of
      single-particle energy dispersions in certain solid state materials (named Weyl
      semimetals), similar as graphene for Dirac fermions. Here we show that such Weyl
      semimetals also exist in the quasiparticle excitation spectrum of a three
      dimensional spin-orbit-coupled Fulde-Ferrell superfluid. By varying Zeeman
      fields, the properties of Weyl fermions, such as their creation and annihilation,
      number and position, as well as anisotropic linear dispersions around band
      touching points, can be tuned. We study the manifestation of anisotropic Weyl
      fermions in sound speeds of Fulde-Ferrell fermionic superfluids, which are
      detectable in experiments. 

PMID- 24745444
TI  - Interstitial channels that control band gaps and effective masses in
      tetrahedrally bonded semiconductors.
AB  - We find that electron states at the bottom of the conduction bands of covalent
      semiconductors are distributed mainly in the interstitial channels and that this
      floating nature leads to the band-gap variation and the anisotropic effective
      masses in various polytypes of SiC. We find that the channel length, rather than
      the hexagonality prevailed in the past, is the decisive factor for the band-gap
      variation in the polytypes. We also find that the floating nature causes two
      dimensional electron and hole systems at the interface of different SiC polytypes
      and even one-dimensional channels near the inclined SiC surface. 

PMID- 24745445
TI  - Seebeck effect at the atomic scale.
AB  - The atomic variations of electronic wave functions at the surface and electron
      scattering near a defect have been detected unprecedentedly by tracing
      thermoelectric voltages given a temperature bias [Cho et al., Nat. Mater. 12, 913
      (2013)]. Because thermoelectricity, or the Seebeck effect, is associated with
      heat-induced electron diffusion, how the thermoelectric signal is related to the
      atomic-scale wave functions and what the role of the temperature is at such a
      length scale remain very unclear. Here we show that coherent electron and heat
      transport through a pointlike contact produces an atomic Seebeck effect, which is
      described by the mesoscopic Seebeck coefficient multiplied by an effective
      temperature drop at the interface. The mesoscopic Seebeck coefficient is
      approximately proportional to the logarithmic energy derivative of local density
      of states at the Fermi energy. We deduced that the effective temperature drop at
      the tip-sample junction could vary at a subangstrom scale depending on atom-to
      atom interaction at the interface. A computer-based simulation method of
      thermoelectric images is proposed, and a point defect in graphene was identified
      by comparing experiment and the simulation of thermoelectric imaging.

PMID- 24745446
TI  - Spin-orbit interaction and isotropic electronic transport in graphene.
AB  - Broken symmetries in graphene affect the massless nature of its charge carriers.
      We present an analysis of scattering by defects in graphene in the presence of
      spin-orbit interactions (SOIs). A characteristic constant ratio (?2) of the
      transport to elastic times for massless electrons signals the anisotropy of the
      scattering. We show that SOIs lead to a drastic decrease of this ratio,
      especially at low carrier concentrations, while the scattering becomes
      increasingly isotropic. As the strength of the SOI determines the energy (carrier
      concentration) where this drop is more evident, this effect could help evaluate
      these interactions through transport measurements in graphene systems with
      enhanced spin-orbit coupling. 

PMID- 24745447
TI  - One-dimensional quantum wire formed at the boundary between two insulating
      LaAlO3/SrTiO3 interfaces.
AB  - We grow a tiled structure of insulating two-dimensional LaAlO3/SrTiO3 interfaces
      composed of alternating one and three LaAlO3 unit cells. The boundary between two
      tiles is conducting. At low temperatures this conductance exhibits quantized
      steps as a function of gate voltage indicative of a one-dimensional channel. The
      step size of half the quantum of conductance is evidence for the absence of spin
      degeneracy. 

PMID- 24745448
TI  - Robust protection from backscattering in the topological insulator
      Bi1.5Sb0.5Te1.7Se1.3.
AB  - Electron scattering in the topological surface state (TSS) of the topological
      insulator Bi1.5Sb0.5Te1.7Se1.3 was studied using quasiparticle interference
      observed by scanning tunneling microscopy. It was found that not only the 180
      degrees  backscattering but also a wide range of backscattering angles of 100
      degrees -180 degrees  are effectively prohibited in the TSS. This conclusion was
      obtained by comparing the observed scattering vectors with the diameters of the
      constant-energy contours of the TSS, which were measured for both occupied and
      unoccupied states using time- and angle-resolved photoemission spectroscopy. The
      robust protection from backscattering in the TSS is good news for applications,
      but it poses a challenge to the theoretical understanding of the transport in the
      TSS. 

PMID- 24745449
TI  - Mapping the topological phase diagram of multiband semiconductors with
      supercurrents.
AB  - We show that Josephson junctions made of multiband semiconductors with strong
      spin-orbit coupling carry a critical supercurrent Ic that contains information
      about the nontrivial topology of the system. In particular, we find that the
      emergence and annihilation of Majorana bound states in the junction is reflected
      in strong even-odd effects in Ic at small junction transparency. This effect
      allows for a mapping between Ic and the topological phase diagram of the
      junction, thus providing a dc measurement of its topology. 

PMID- 24745451
TI  - Chiral spin liquid in a frustrated anisotropic kagome Heisenberg model.
AB  - Kalmeyer-Laughlin (KL) chiral spin liquid (CSL) is a type of quantum spin liquid
      without time-reversal symmetry, and it is considered as the parent state of an
      exotic type of superconductor--anyon superconductor. Such an exotic state has
      been sought for more than twenty years; however, it remains unclear whether it
      can exist in a realistic system where time-reversal symmetry is breaking (T
      breaking) spontaneously. By using the density matrix renormalization group, we
      show that KL CSL exists in a frustrated anisotropic kagome Heisenberg model,
      which has spontaneous T breaking. We find that our model has two topological
      degenerate ground states, which exhibit nonvanishing scalar chirality order and
      are protected by finite excitation gap. Furthermore, we identify this state as KL
      CSL by the characteristic edge conformal field theory from the entanglement
      spectrum and the quasiparticles braiding statistics extracted from the modular
      matrix. We also study how this CSL phase evolves as the system approaches the
      nearest-neighbor kagome Heisenberg model.

PMID- 24745450
TI  - Magneto- to electroactive transmutation of spin waves in ErMnO3.
AB  - The low-energy dynamical properties of the multiferroic hexagonal perovskite
      ErMnO3 have been studied by inelastic neutron scattering as well as terahertz and
      far infrared spectroscopies on a synchrotron source. From these complementary
      techniques, we have determined the magnon and crystal field spectra and
      identified a zone center magnon excitable only by the electric field of an
      electromagnetic wave. Using a comparison with the isostructural YMnO3 compound
      and crystal field calculations, we propose that this dynamical magnetoelectric
      process is due to the hybridization of a magnon with an electroactive crystal
      field transition. 

PMID- 24745452
TI  - ZnO as a tunable metal: new types of surface plasmon polaritons.
AB  - The use of the free-electron gas in a heavily doped semiconductor (ZnO:Ga)
      enables the realization of almost arbitrarily shaped surface-plasmon-polariton
      dispersion curves in planar geometries. In particular, by preparing metal-metal
      type interfaces, we demonstrate surface-plasmon polaritons exhibiting finite
      frequencies in the long-wavelength limit. Moreover, coupling of surface plasmon
      polaritons at adjacent interfaces allows for the controlled formation of
      frequency gaps or, alternatively, the opening of otherwise forbidden regions by
      an appropriate layer design. Our findings reveal a considerable plasmonic
      potential of this semiconductor-based approach, e.g., for achieving propagation
      control or phase matching for nonlinear optical processes as well as novel many
      particle phenomena. 

PMID- 24745453
TI  - Singlet-triplet annihilation limits exciton yield in poly(3-hexylthiophene).
AB  - Control of chain length and morphology in combination with single-molecule
      spectroscopy techniques provides a comprehensive photophysical picture of excited
      state losses in the prototypical conjugated polymer poly(3-hexylthiophene)
      (P3HT). Our examination reveals a universal self-quenching mechanism, based on
      singlet-triplet exciton annihilation, which accounts for the dramatic loss in
      fluorescence quantum yield of a single P3HT chain between its solution (unfolded)
      and bulklike (folded) state. Triplet excitons fundamentally limit the
      fluorescence of organic photovoltaic materials, which impacts the conversion of
      singlet excitons to separated charge carriers, decreasing the efficiency of
      energy harvested at high excitation densities. Interexcitonic interactions are so
      effective that a single P3HT chain of order 100  kDa weight behaves like a 2
      level system, exhibiting perfect photon antibunching. 

PMID- 24745454
TI  - Hierarchy of bound states in the one-dimensional ferromagnetic Ising chain
      CoNb2O6 investigated by high-resolution time-domain terahertz spectroscopy.
AB  - Kink bound states in the one-dimensional ferromagnetic Ising chain compound
      CoNb2O6 have been studied using high-resolution time-domain terahertz
      spectroscopy in zero applied magnetic field. When magnetic order develops at low
      temperature, nine bound states of kinks become visible. Their energies can be
      modeled exceedingly well by the Airy function solutions to a 1D Schrodinger
      equation with a linear confining potential. This sequence of bound states
      terminates at a threshold energy near 2 times the energy of the lowest bound
      state. Above this energy scale we observe a broad feature consistent with the
      onset of the two particle continuum. At energies just below this threshold we
      observe a prominent excitation that we interpret as a novel bound state of bound
      states--two pairs of kinks on neighboring chains.

PMID- 24745455
TI  - Critical behavior of a noncritical field: destruction of smectic order at the
      smectic A-C tricritical point and implications for de Vries behavior.
AB  - Critical behavior near the smectic A-C tricritical point is studied using
      renormalization group techniques. Critical fluctuations induce a singular
      softening of the smectic bulk modulus in the A phase. At the tricritical point,
      the quasi-long-range positional order of the smectic layers is destroyed. Despite
      this loss of order, dislocations remain bound so that smectic elasticity is
      retained but becomes anomalous, i.e., length scale dependent. The critically
      induced large layer fluctuations lead to negative thermal expansion of the layers
      in the A phase and may explain the origin of de Vries behavior. Experimental
      predictions are given for the temperature dependence of the smectic bulk modulus,
      x-ray structure factor, and layer spacing in the A phase. 

PMID- 24745456
TI  - Elastocapillary snapping: capillarity induces snap-through instabilities in small
      elastic beams.
AB  - We report on the capillarity-induced snapping of elastic beams. We show that a
      millimeter-sized water drop gently deposited on a thin buckled polymer strip may
      trigger an elastocapillary snap-through instability. We investigate
      experimentally and theoretically the statics and dynamics of this phenomenon and
      we further demonstrate that snapping can act against gravity, or be induced by
      soap bubbles on centimeter-sized thin metal strips. We argue that this phenomenon
      is suitable to miniaturization and design a condensation-induced spin-off version
      of the experiment involving a hydrophilic strip placed in a steam flow. 

PMID- 24745457
TI  - Continuous and discontinuous dynamic unbinding transitions in drawn film flow.
AB  - When a plate is withdrawn from a liquid bath a coating layer is deposited whose
      thickness and homogeneity depend on the velocity and the wetting properties of
      the plate. Using a long-wave mesoscopic hydrodynamic description that
      incorporates wettability via a Derjaguin (disjoining) pressure we identify four
      qualitatively different dynamic transitions between microscopic and macroscopic
      coatings that are out-of-equilibrium equivalents of known equilibrium unbinding
      transitions. Namely, these are continuous and discontinuous dynamic wetting and
      emptying transitions. Several of their features have no equivalent at
      equilibrium. 

PMID- 24745458
TI  - Evidence of disorder in biological molecules from single molecule pulling
      experiments.
AB  - Heterogeneity in biological molecules, resulting in molecule-to-molecule
      variations in their dynamics and function, is an emerging theme. To elucidate the
      consequences of heterogeneous behavior at the single molecule level, we propose
      an exactly solvable model in which the unfolding rate due to mechanical force
      depends parametrically on an auxiliary variable representing an entropy barrier
      arising from fluctuations in internal dynamics. When the rate of fluctuations--a
      measure of dynamical disorder--is comparable to or smaller than the rate of force
      induced unbinding, we show that there are two experimentally observable
      consequences: nonexponential survival probability at constant force, and a heavy
      tailed rupture force distribution at constant loading rate. By fitting our
      analytical expressions to data from single molecule pulling experiments on
      proteins and DNA, we quantify the extent of disorder. We show that only by
      analyzing data over a wide range of forces and loading rates can the role of
      disorder due to internal dynamics be quantitatively assessed.

PMID- 24745459
TI  - Asymmetric mutualism in two- and three-dimensional range expansions.
AB  - Genetic drift at the frontiers of two-dimensional range expansions of
      microorganisms can frustrate local cooperation between different genetic
      variants, demixing the population into distinct sectors. In a biological context,
      mutualistic or antagonistic interactions will typically be asymmetric between
      variants. By taking into account both the asymmetry and the interaction strength,
      we show that the much weaker demixing in three dimensions allows for a
      mutualistic phase over a much wider range of asymmetric cooperative benefits,
      with mutualism prevailing for any positive, symmetric benefit. We also
      demonstrate that expansions with undulating fronts roughen dramatically at the
      boundaries of the mutualistic phase, with severe consequences for the population
      genetics along the transition lines. 

PMID- 24745460
TI  - Inhibition causes ceaseless dynamics in networks of excitable nodes.
AB  - The collective dynamics of a network of excitable nodes changes dramatically when
      inhibitory nodes are introduced. We consider inhibitory nodes which may be
      activated just like excitatory nodes but, upon activating, decrease the
      probability of activation of network neighbors. We show that, although the direct
      effect of inhibitory nodes is to decrease activity, the collective dynamics
      becomes self-sustaining. We explain this counterintuitive result by defining and
      analyzing a "branching function" which may be thought of as an activity-dependent
      branching ratio. The shape of the branching function implies that, for a range of
      global coupling parameters, dynamics are self-sustaining. Within the self
      sustaining region of parameter space lies a critical line along which dynamics
      take the form of avalanches with universal scaling of size and duration, embedded
      in a ceaseless time series of activity. Our analyses, confirmed by numerical
      simulation, suggest that inhibition may play a counterintuitive role in excitable
      networks. 

PMID- 24745461
TI  - Universal area distributions in the monolayers of confluent mammalian cells.
AB  - When mammalian cells form confluent monolayers completely filling a plane, these
      apparently random "tilings" show regularity in the statistics of cell areas for
      various types of epithelial and endothelial cells. The observed distributions are
      reproduced by a model which accounts for cell growth and division, with the
      latter treated stochastically both in terms of the sizes of the dividing cells as
      well as the sizes of the "newborn" ones--remarkably, the modeled and experimental
      distributions fit well when all free parameters are estimated directly from
      experiments.

PMID- 24745462
TI  - DNA damage by OH radicals produced using intense, ultrashort, long wavelength
      laser pulses.
AB  - We probe femtosecond laser induced damage to aqueous DNA, relying on strong-field
      interaction with water wherein electrons and free radicals are generated in situ;
      these, in turn, interact with DNA plasmids under physiological conditions,
      producing nicks. Exposure to intense femtosecond pulses of 1350 and 2200 nm light
      induces single strand breaks and double strand breaks (DSBs) in DNA. At the
      longer wavelength (and at higher intensities), rotationally hot OH radicals
      induce DSBs, producing linear DNA. Strand breaks occur due to single or multiple
      OH hits on DNA. With 2200 nm light, DSBs are formed mostly by the action of two
      OH radicals; use of OH scavengers establishes that the probability of a two-hit
      event reduces much faster than a one-hit event as scavenger concentration is
      increased. Thermal effects do not induce DSBs with 2200 nm light. 

PMID- 24745463
TI  - Complex dynamics of compound vesicles in linear flow.
AB  - We report first experimental observations of dynamics of compound vesicles in
      linear flow realized in a microfluidic four-roll mill. We show that while a
      compound vesicle undergoes the same main tank-treading, trembling (TR), and
      tumbling regimes, its dynamics are far richer and more complex than that of
      unilamellar vesicles. A new swinging motion of the inner vesicle is found in TR
      in accord with simulations. The inner and outer vesicles can exist simultaneously
      in different dynamical regimes and can undergo either synchronized or
      unsynchronized motions depending on the filling factor. A compound vesicle can be
      used as a physical model to study white blood cell dynamics in flow similar to a
      unilamellar vesicle used successfully to model anucleate cells. 

PMID- 24745464
TI  - Critical bottleneck size for jamless particle flows in two dimensions.
AB  - We propose a simple microscopic model for arching phenomena at bottlenecks. The
      dynamics of particles in front of a bottleneck is described by a one-dimensional
      stochastic cellular automaton on a semicircular geometry. The model reproduces
      oscillation phenomena due to the formation and collapsing of arches. It predicts
      the existence of a critical bottleneck size for continuous particle flows. The
      dependence of the jamming probability on the system size is approximated by the
      Gompertz function. The analytical results are in good agreement with simulations.

PMID- 24745465
TI  - Somatic symptoms and health-related quality of life among treatment-seeking
      Canadian Forces personnel with PTSD.
AB  - This study examined the association between somatic complaints and health-related
      quality of life (HR-QoL) in treatment-seeking Canadian military personnel with
      military-related Posttraumatic Stress Disorder (PTSD). Current and former
      Canadian Forces (CF) members attending the Parkwood Hospital Operational Stress
      Injury Clinic in London, Ontario (N=291) were administered self-report
      questionnaires assessing number and severity of somatic complaints, PTSD and
      depressive symptom severity, and mental and physical health-related quality of
      life (HR-QoL) prior to commencing treatment. Regression analyses were used to
      identify the role of somatic complaints on physical and mental HR-QoL, after
      controlling for PTSD symptom cluster and depressive symptom severity. Somatic
      symptom severity accounted for only a small amount of the variance in mental HR
      QoL after accounting for PTSD symptom cluster and depressive symptom severity,
      but accounted for a larger proportion of the variance in physical HR-QoL after
      accounting for PTSD cluster and depressive symptom severity. Understanding the
      role of somatization in the symptom-presentation of military personnel with PTSD
      may provide additional avenues for treatment with this population. 

PMID- 24745466
TI  - Scoring rules and rating formats of Self-report Depression Questionnaires: a
      comparison of approaches.
AB  - Self-report measures of depression differ in their construction and scoring
      rules. In the present study from the Rhode Island Methods to Improve Diagnostic
      Assessment and Services (MIDAS) project we tested the hypothesis that the loss of
      information due to scoring rules or rating formats reduces the validity of
      depression severity assessment. One hundred fifty-three outpatients with DSM-IV
      major depressive disorder (MDD) who presented for treatment or who were in
      ongoing treatment and had their medication changed due to lack of efficacy
      completed the Clinically Useful Depression Outcome Scale (CUDOS), Quick Inventory
      of Depressive Symptomatology (QIDS) and Remission from Depression Questionnaire
      (RDQ) at the initiation of treatment and 4 month follow-up. The patients were
      evaluated with the 17-item Hamilton Depression scale (HAMD). The CUDOS and RDQ
      were equally highly correlated with the HAMD at baseline and follow-up. There was
      no significant difference in the correlations between the modified and original
      scoring algorithms of the QIDS with the HAMD at baseline and the follow-up. On
      each scale, the patients showed significant levels of improvement from baseline
      to 4 months, and the effect sizes were similar. These findings suggest that the
      loss of information due to the scoring rules of the QIDS or the rating format of
      the RDQ did not reduce the validity of depression severity assessment. 

PMID- 24745467
TI  - The impact of social content and negative symptoms on affective ratings in
      schizophrenia.
AB  - The anhedonia paradox has been a topic of ongoing study in schizophrenia.
      Previous research has found that schizophrenia patients report less enjoyment
      from various activities when compared to their healthy counterparts; however, the
      two groups appear to have similar in-the-moment emotional ratings of these events
      (Gard et al., 2007; Herbener et al., 2007; Horan et al., 2006). This study
      examined these in-the-moment experiences further, by assessing whether they
      differed between social and non-social experiences. The data were collected from
      38 individuals with schizophrenia and 53 matched healthy controls in the greater
      Chicago area. In-the-moment emotional experience was measured by self-reported
      arousal and valence ratings for social and non-social stimuli taken from the
      International Affective Picture System (IAPS). Clinical ratings for patients were
      gathered by the Positive and Negative Syndrome Scale. A series of ANOVAs revealed
      that controls were more aroused by the social than nonsocial unpleasant stimuli,
      whereas patients did not show this distinction. Further, regression analyses
      revealed that negative symptom severity uniquely predicted lower arousal
      responses to unpleasant social, but not nonsocial, stimuli. Our results indicate
      that both subject and stimulus factors appear to contribute to differences in
      emotional responses in individuals with schizophrenia. 

PMID- 24745468
TI  - When the lie is the truth: grounded theory analysis of an online support group
      for factitious disorder.
AB  - Factitious disorder (FD) is poorly understood because of the elusiveness of
      sufferers. What is known is based on speculation from observational case studies
      and this is evident by the manifold diagnostic and treatment issues associated
      with FD. This study sought to fill the gap in the literature and overcome the
      elusiveness of FD sufferers by analysing their text communications in two online
      communities. One hundred twenty four posts by 57 members amounting to
      approximately 38,000 words were analysed using grounded theory. The analysis
      showed that contrary to current theories of FD, motivation is conscious and not
      unconscious, members did experience symptoms associated with the disorder, and
      they were also upset by their behaviour and wanted to recover but were deterred
      by fear. Furthermore, using the excessive appetitive model by Orford (2001) it is
      hypothesised that the characteristics of FD described by the members were
      congruent with those associated with addiction. 

PMID- 24745469
TI  - Blood-cerebrospinal fluid barrier dysfunction in patients with bipolar disorder
      in relation to antipsychotic treatment.
AB  - Blood-cerebrospinal barrier (BCB) dysfunction has previously been shown in
      subjects with schizophrenia and depressed patients with attempted suicide.
      Bipolar disorder (BPD) shares clinical features with both these disorders, but it
      is unknown if the integrity of the BCB is altered also in BPD. To assess if BCB
      function in BPD we surveyed 134 mood-stabilized BPD patients and 86 healthy
      controls. Serum and cerebrospinal fluid (CSF) samples were collected and analyzed
      for albumin concentration by immunonephelometry. CSF/serum albumin ratio, an
      established measure of BCB function, was significantly elevated in BPD patients
      as compared to controls. After stratifying patients according to diagnostic
      subtype, BPD I patients had the highest CSF/serum albumin ratios. Moreover, BPD
      patients on antipsychotic treatment had higher CSF/serum albumin ratio than BPD
      patients on other treatments. When excluding BPD patients on antipsychotic
      treatment the difference in CSF/serum albumin ratio between the BPD and control
      groups disappeared. In conclusion, antipsychotic treatment in BPD is associated
      with elevated CSF/serum albumin ratio, tentatively as a sign of impaired BCB
      function. Whether this elevation is caused by antipsychotic treatment or is
      associated with a certain subtype of BPD, requiring antipsychotic treatment,
      remains to be determined. 

PMID- 24745470
TI  - Anxiety mediates the association between cannabis use and attenuated positive
      psychotic symptoms.
AB  - Cannabis use has been associated with a continuum of psychotic experiences.
      However, it is unclear whether mood and anxiety symptoms account for increases in
      attenuated positive psychotic symptoms (APPS) among cannabis users. We predicted
      that depression and anxiety symptoms would mediate the relation between cannabis
      use and APPS, and between cannabis use and endorsement of eight or more
      distressing APPS (D-APPS), a potentially more clinically meaningful group. Young
      adults (n=674) completed the Prodromal Questionnaire (PQ); Drug Use Frequency
      measure; Center for Epidemiologic Studies Depression Scale; State-Trait Anxiety
      Inventory, Trait Form, Anxiety Subscale; and Social Phobia Scale. Results
      indicated that symptoms of trait anxiety, but not symptoms of depression or
      social anxiety, mediated the relationship between cannabis use and APPS, as well
      as the relationship between cannabis use and D-APPS. Results indicate that
      symptoms of trait anxiety may play a role in the relation between cannabis use
      and APPS. Findings underscore the importance of considering clinical
      characteristics co-occurring with psychotic symptoms, such as affective symptoms,
      when examining the association between cannabis use and psychotic symptoms. 

PMID- 24745472
TI  - Theory of mind reasoning in schizophrenia patients and non-psychotic relatives.
AB  - Research consistently demonstrates that schizophrenia patients have theory of
      mind (ToM) impairments. Additionally, there is some evidence that family members
      of schizophrenia patients also demonstrate impairments in ToM, suggesting a
      genetic vulnerability for the disorder. This study assessed ToM abilities (i.e.,
      sarcasm comprehension) in schizophrenia patients and their first-degree
      biological relatives during video-taped social interactions, to be representative
      of real-world interactions and to assess for disease-specific and/or genetic
      liability effects. Additionally, we assessed whether ToM abilities predicted
      social and global functioning in schizophrenia patients, and whether symptoms
      were associated with ToM deficits. Schizophrenia patients demonstrated
      impairments in sarcasm comprehension compared to controls and relatives, whereas
      relatives showed intact comprehension. Symptoms of schizophrenia significantly
      predicted worse ToM abilities. Furthermore, in schizophrenia patients, impaired
      ToM reasoning predicted worse social and global functioning. Given schizophrenia
      patients demonstrated impairments in ToM reasoning in a task that resembles real
      life interactions, this might be a key area for remediation. 

PMID- 24745471
TI  - The BDNF Val66Met polymorphism does not moderate the effect of self-reported
      physical activity on depressive symptoms in midlife.
AB  - The brain-derived neurotrophic factor (BDNF) Val66Met single nucleotide
      polymorphism may be associated with clinical and subsyndromal depression, but
      physical activity improves mood and increases BDNF expression. The aim of the
      study was to examine whether the BDNF polymorphism moderates an effect of
      physical activity on depressive symptoms. BDNF genotype, physical activity
      measured by the Paffenbarger Questionnaire, and depressive symptoms using the
      Center for Epidemiology Depression Scale (CES-D) were collected on 1072
      participants (mean age=44). Multiple linear regression was used to examine the
      association between BDNF genotype, physical activity, and depressive symptoms.
      After adjusting for family income, age, and education, depressive symptoms were
      higher in Met carriers compared to Val homozygotes (p=0.03), but this was only
      significant in men. Physical activity was associated with fewer depressive
      symptoms, but only in women (p=0.01). BDNF genotype did not moderate the effect
      of physical activity on depressive symptoms (p=0.94). In midlife, the BDNF
      Val66Met polymorphism neither attenuates nor magnifies the effect of physical
      activity on depressive symptoms. 

PMID- 24745473
TI  - Assessing the relation between career satisfaction in psychiatry with lifelong
      learning and scientific activity.
AB  - Lifelong learning (LLL) is an essential feature for the doctor to keep clinically
      updated and has been described as an indicator of competence and professionalism.
      The aim of this study was to evaluate the association between career satisfaction
      in psychiatry, lifelong learning, and commitment in scientific activities, taking
      into account other personal and professional effects. The survey was sent to 453
      national psychiatrists and 190 surveys (41.9%) were completed online and
      validated. The Jefferson Scale of Physician Lifelong Learning (JSPLL) was used to
      assess the level of LLL for each doctor. The results of the analysis of JSPLL
      showed that participants more satisfied with their career have greater motivation
      and invest more in the LLL. Furthermore, participants who were more satisfied
      with their career had a higher percentage of scientific activity in the last
      year. Multiple linear regression with these two effects in the model revealed a
      positive association between career satisfaction in psychiatry, LLL and the
      publication of scientific papers, leading to the main conclusion that
      satisfaction with a career in psychiatry has a significant correlation with LLL
      and with involvement in scientific activities. 

PMID- 24745474
TI  - The role of executive attention in deliberate self-harm.
AB  - Although a wealth of literature has examined the role of emotion-related factors
      in deliberate self-harm (DSH), less is known about neurocognitive factors and
      DSH. In particular, despite theoretical literature suggesting that deficits in
      executive attention may contribute to engagement in DSH, studies have not yet
      examined the functioning of this attentional network among individuals with DSH.
      The present study sought to address this gap in the literature by examining the
      functioning of the alerting, orienting, and executive attentional networks among
      participants with a recent history of DSH (n=15), a past history of DSH (n=18),
      and no history of DSH (n=21). Controlling for borderline personality pathology
      and depression symptoms, participants with a recent history of DSH exhibited
      deficits in executive attention functioning relative to participants without any
      history of DSH. No differences were found in terms of performance on the alerting
      or orienting attentional networks. These results provide preliminary support for
      the association between executive attention deficits and DSH. 

PMID- 24745475
TI  - Patterns of substance use among HIV-positive adults over 50: implications for
      treatment and medication adherence.
AB  - BACKGROUND: The population of older adults living with HIV is increasing in the
      United States. Despite an increased focus on the health of HIV-positive older
      adults, knowledge about their substance use, a primary risk factor for HIV
      medication non-adherence, and the association between use, problems associated
      with use, and adherence behavior, is limited. METHODS: Data were collected from
      557 HIV-positive adults aged 50 and older in the New York City area via telephone
      interview. Participants reported the number of days in the past month on which
      they missed any doses of HIV medication as well as the number of days they used
      alcohol, marijuana, cocaine/crack, opiates, amyl nitrite (poppers), and other
      drugs. The severity of substance use associated problems was assessed using the
      DAST-10 and AUDIT-C. RESULTS: The sample included gay/bisexual (40.4%) and
      heterosexual (28.1%) men as well as lesbian/bisexual (4.9%) and heterosexual
      (26.7%) women. Latent class analyses identified four distinct patterns of
      substance use: Exclusive Alcohol Use; Alcohol and Marijuana; Alcohol and
      Cocaine/Crack; and Multiple-Substance Use. Variability in the number of missed
      HIV medication days and perceptions of substance use associated problems were
      observed across classes, with poorest adherence reported in the Alcohol and
      Marijuana class, the Alcohol and Cocaine/Crack class, and the Multiple-Substance
      Use class. The latter two classes also reported the greatest perceived impairment
      from substance use. CONCLUSIONS: Patterns of recent substance use were associated
      with varying levels of HIV medication adherence and perceived substance use
      impairment, indicating that substance type matters when considering the health of
      older adults living with HIV, and that multiple-substance use needs to be
      addressed by interventions aimed at improving medication adherence.

PMID- 24745476
TI  - Changes in resting functional connectivity during abstinence in stimulant use
      disorder: a preliminary comparison of relapsers and abstainers.
AB  - BACKGROUND: Previously identified resting functional connectivity (FC)
      differences in individuals with stimulant use disorder (SUD) suggest an imbalance
      in neural regions that mediate behavioral aspects relevant to addiction such as
      emotion regulation and reward processing. There is a need to further investigate
      these differences across time between those that relapse and those that do not.
      This is the first longitudinal study of recently abstinent SUD (SUD-RA) that
      identifies specific FC changes in subsequent relapsers (vs abstainers). We
      hypothesized that (1) subsequent relapsers (vs abstainers) will show lower FC of
      emotion regulation regions and higher FC of reward processing regions and (2) FC
      differences would be more evident across time. METHODS: We examined resting FC in
      18 SUD-RAs (8 females, age: M=22.05 +/- 2.64) and 15 non-substance abusing
      controls (NSAC; 5 females, age: M=24.21 +/- 5.76) at Time 1 (abstinent ~5 weeks).
      Fourteen NSAC and 12 SUD-RAs were re-examined at Time 2 (abstinent ~13 weeks).
      With seed-based FC measures, we examined FC differences between SUD-RAs that
      abstained or relapsed over the subsequent 6 months. RESULTS: Relapsers (vs
      abstainers) had higher FC between (1) nucleus accumbens (NAcc) and left
      frontopolar cortex (FPC), (2) NAcc and posterior cingulate gyrus and (3)
      subgenual anterior cingulate and left FPC at Time 1. Relapsers (vs abstainers)
      showed larger reduction in FC strength within these regions across time.
      CONCLUSIONS: Resting FC reduction found in relapsers (vs. abstainers) from 5 to
      13 weeks of abstinence may be a biological marker of relapse vulnerability. These
      preliminary findings require replication with larger sample sizes.

PMID- 24745478
TI  - Informal mobile learning in nurse education and practice in remote areas--a case
      study from rural South Africa.
AB  - BACKGROUND: With the proliferation of portable digital technology, mobile
      learning is becoming increasingly popular in nursing education and practice. Most
      of the research in this field has been concentrated on small-scale projects in
      high income countries. Very little is known about the ways in which nurses and
      midwives use mobile technology in remote and resource poor areas in informal
      learning contexts in low and middle income countries. OBJECTIVES: To address this
      gap, this study investigates whether nurses use mobile phones as effective
      educational tools in marginalized and remote areas, and if so, how and why.
      SETTING AND METHODS: In rural South Africa, 16 nurses who attended an advanced
      midwifery education program, facilitators and clinical managers were interviewed
      about their use of digital mobile technology for learning. Techniques of
      qualitative content analysis were used to examine the data. RESULTS: Several rich
      "organically-grown", learning practices were identified: mobile phone usage
      facilitated (1) authentic problem solving; (2) reflective practice; (3) emotional
      support and belongingness; (4) the realization of unpredictable teaching
      situations; and (5) life-long learning. CONCLUSIONS: It is concluded that mobile
      phones, and the convergence of mobile phones and social media, in particular,
      change learning environments. In addition, these tools are suitable to connect
      learners and learning distributed in marginalized areas. Finally, a few
      suggestions are made about how these insights from informal settings can inform
      the development of more systematic mobile learning formats.

PMID- 24745480
TI  - Re: management of localized kidney cancer: calculating cancer-specific mortality
      and competing risks of death for surgery and nonsurgical management.

PMID- 24745481
TI  - Re: adrenal cysts: natural history by long-term imaging follow-up.

PMID- 24745479
TI  - Identification of novel molecular regulators of tumor necrosis factor-related
      apoptosis-inducing ligand (TRAIL)-induced apoptosis in breast cancer cells by
      RNAi screening.
AB  - INTRODUCTION: Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)
      binds to its receptors, TRAIL-receptor 1 (TRAIL-R1) and TRAIL-receptor 2 (TRAIL
      R2), leading to apoptosis by activation of caspase-8 and the downstream
      executioner caspases, caspase-3 and caspase-7 (caspase-3/7). Triple-negative
      breast cancer (TNBC) cell lines with a mesenchymal phenotype are sensitive to
      TRAIL, whereas other breast cancer cell lines are resistant. The underlying
      mechanisms that control TRAIL sensitivity in breast cancer cells are not well
      understood. Here, we performed small interfering RNA (siRNA) screens to identify
      molecular regulators of the TRAIL pathway in breast cancer cells. METHODS: We
      conducted siRNA screens of the human kinome (691 genes), phosphatome (320 genes),
      and about 300 additional genes in the mesenchymal TNBC cell line MB231. Forty
      eight hours after transfection of siRNA, parallel screens measuring caspase-8
      activity, caspase-3/7 activity, or cell viability were conducted in the absence
      or presence of TRAIL for each siRNA, relative to a negative control siRNA
      (siNeg). A subset of genes was screened in cell lines representing epithelial
      TNBC (MB468), HER2-amplified breast cancer (SKBR3), and estrogen receptor
      positive breast cancer (T47D). Selected putative negative regulators of the TRAIL
      pathway were studied by using small-molecule inhibitors. RESULTS: The primary
      screens in MB231 identified 150 genes, including 83 kinases, 4 phosphatases, and
      63 nonkinases, as potential negative regulators of TRAIL. The identified genes
      are involved in many critical cell processes, including apoptosis, growth factor
      receptor signaling, cell-cycle regulation, transcriptional regulation, and DNA
      repair. Gene-network analysis identified four genes (PDPK1, IKBKB, SRC, and
      BCL2L1) that formed key nodes within the interaction network of negative
      regulators. A secondary screen of a subset of the genes identified in additional
      cell lines representing different breast cancer subtypes and sensitivities to
      TRAIL validated and extended these findings. Further, we confirmed that small
      molecule inhibition of SRC or BCL2L1, in combination with TRAIL, sensitizes
      breast cancer cells to TRAIL-induced apoptosis, including cell lines resistant to
      TRAIL-induced cytotoxicity. CONCLUSIONS: These data identify novel molecular
      regulators of TRAIL-induced apoptosis in breast cancer cells and suggest
      strategies for the enhanced application of TRAIL as a therapy for breast cancer.

PMID- 24745483
TI  - Re: recurrence of high-risk bladder cancer: a population-based analysis.

PMID- 24745484
TI  - Re: tracking the clonal origin of lethal prostate cancer.

PMID- 24745485
TI  - Re: decision making in prostate cancer screening using decision aids vs usual
      care: a randomized clinical trial.

PMID- 24745486
TI  - Re: prostate cancer imaging trends after a nationwide effort to discourage
      inappropriate prostate cancer imaging.

PMID- 24745487
TI  - Re: a prospective, blinded comparison of magnetic resonance (MR) imaging
      ultrasound fusion and visual estimation in the performance of MR-targeted
      prostate biopsy: the PROFUS trial.

PMID- 24745488
TI  - Re: use of statins and the risk of death in patients with prostate cancer.

PMID- 24745489
TI  - Re: perioperative outcomes for laparoscopic and robotic compared with open
      prostatectomy using the national surgical quality improvement program (NSQIP)
      database.

PMID- 24745490
TI  - Re: predicting risk of prostate cancer in men receiving finasteride: effect of
      prostate volume, number of biopsy cores, and american urological association
      symptom score.

PMID- 24745491
TI  - Re: TOOKAD(r) soluble vascular-targeted photodynamic (VTP) therapy: determination
      of optimal treatment conditions and assessment of effects in patients with
      localised prostate cancer.

PMID- 24745492
TI  - Re: use of a hyaluronic acid-carboxymethylcellulose adhesion barrier on the
      neurovascular bundle and prostatic bed to facilitate earlier recovery of erectile
      function after robot-assisted prostatectomy: an initial experience.

PMID- 24745493
TI  - Re: variation among primary care physicians in prostate-specific antigen
      screening of older men.

PMID- 24745494
TI  - Re: continuing cancer screening later in life: attitudes and intentions among
      older adults in England.

PMID- 24745495
TI  - Re: urologists' use of intensity-modulated radiation therapy for prostate cancer.

PMID- 24745496
TI  - Re: testicular cancer in Europe and the USA: survival still rising among older
      patients.

PMID- 24745498
TI  - Re: voided midstream urine culture and acute cystitis in premenopausal women.

PMID- 24745499
TI  - Re: dermatopathology of the foreskin: an institutional experience of over 400
      cases.

PMID- 24745500
TI  - Re: urethroplasty practice and surveillance patterns: a survey of reconstructive
      urologists.

PMID- 24745501
TI  - Re: management of anastomotic stricture after artificial urinary sphincter
      placement in patients who underwent salvage prostatectomy.

PMID- 24745502
TI  - Re: the utility of abdominal ultrasound during percutaneous suprapubic catheter
      placement.

PMID- 24745503
TI  - Re: botulinum toxin A modulates afferent fibers in neurogenic detrusor
      overactivity.

PMID- 24745504
TI  - Re: the prevalence of lower urinary tract symptoms (LUTS) and overactive bladder
      (OAB) by racial/ethnic group and age: results from OAB-POLL.

PMID- 24745505
TI  - Re: urethral sphincter function before and after radical prostatectomy:
      systematic review of the prognostic value of various assessment techniques.

PMID- 24745506
TI  - Re: urinary incontinence in young nulligravid women: a cross-sectional analysis.

PMID- 24745507
TI  - Re: effect of urinary incontinence on older nursing home residents' self-reported
      quality of life.

PMID- 24745508
TI  - Re: the effect of systematic screening of older women for urinary incontinence on
      treatment uptake: the URINO trial.

PMID- 24745509
TI  - Re: a good alternative to indwelling catheter owing to benign prostate
      hyperplasia in elderly: memotherm prostatic stent.

PMID- 24745510
TI  - Re: beta3-adrenoreceptor agonist mirabegron is effective for overactive bladder
      that is unresponsive to antimuscarinic treatment or is related to benign
      prostatic hyperplasia in men.

PMID- 24745511
TI  - Re: relationship between predictors of the risk of clinical progression of benign
      prostatic hyperplasia and metabolic syndrome in men with moderate to severe lower
      urinary tract symptoms.

PMID- 24745512
TI  - Re: tadalafil once daily for lower urinary tract symptoms suggestive of benign
      prostatic hyperplasia: a randomized placebo- and tamsulosin-controlled 12-week
      study in asian men.

PMID- 24745513
TI  - Re: gonadal steroids and body composition, strength, and sexual function in men.

PMID- 24745514
TI  - Re: 150 minutes of vigorous physical activity per week predicts survival and
      successful ageing: a population-based 11-year longitudinal study of 12 201 older
      Australian men.

PMID- 24745516
TI  - Re: men with diabetes may require more aggressive treatment for erectile
      dysfunction.

PMID- 24745517
TI  - Re: lower plasma testosterone or dihydrotestosterone, but not estradiol, is
      associated with symptoms of intermittent claudication in older men.

PMID- 24745518
TI  - Re: complications associated with retained foreign bodies from infected penile
      implants: proposal for the use of an implant-specific checklist at the time of
      device removal.

PMID- 24745519
TI  - Re: prospective analysis of the surgical outcomes and patients' satisfaction rate
      after the AMS spectra penile prosthesis implantation.

PMID- 24745520
TI  - Re: high submuscular placement of urologic prosthetic balloons and reservoirs via
      transscrotal approach.

PMID- 24745521
TI  - Re: isolation of spermatozoa with low levels of fragmented DNA with the use of
      flow cytometry and sorting.

PMID- 24745522
TI  - Re: zebrafish ciliopathy screen plus human mutational analysis identifies
      C21orf59 and CCDC65 defects as causing primary ciliary dyskinesia.

PMID- 24745523
TI  - Re: epididymal specific, selenium-independent GPX5 protects cells from oxidative
      stress-induced lipid peroxidation and DNA mutation.

PMID- 24745524
TI  - Re: paternal aging and associated intraindividual alterations of global sperm 5
      methylcytosine and 5-hydroxymethylcytosine levels.

PMID- 24745525
TI  - Re: age thresholds for changes in semen parameters in men.

PMID- 24745526
TI  - Re: States with the least restrictive regulations experienced the largest
      increase in patients seen by nurse practitioners.

PMID- 24745527
TI  - Re: variation in surgical-readmission rates and quality of hospital care.

PMID- 24745528
TI  - Re: the consequences of poor communication during transitions from hospital to
      skilled nursing facility: a qualitative study.

PMID- 24745529
TI  - Re: e-prescribing adoption and use increased substantially following the start of
      a federal incentive program.

PMID- 24745530
TI  - Re: a single-center analysis of abdominal imaging in the evaluation of kidney
      transplant recipients.

PMID- 24745531
TI  - Re: the predictive properties of frailty-rating scales in the acute medical unit.

PMID- 24745532
TI  - Re: outcomes of adult dual kidney transplants by KDRI in the United States.

PMID- 24745533
TI  - Re: frailty and early hospital readmission after kidney transplantation.

PMID- 24745534
TI  - Re: acute and delayed vesicoureteral obstruction after endoscopic treatment of
      primary vesicoureteral reflux with dextranomer/hyaluronic acid copolymer: why and
      how to manage.

PMID- 24745535
TI  - Re: randomized clinical trial comparing endoscopic treatment with dextranomer
      hyaluronic acid copolymer and Cohen's ureteral reimplantation for vesicoureteral
      reflux: long-term results.

PMID- 24745536
TI  - Re: long-term incidence of urinary tract infection after ureteral reimplantation
      for primary vesicoureteral reflux.

PMID- 24745537
TI  - Re: postoperative ureteral obstruction after endoscopic treatment of
      vesicoureteral reflux with polyacrylate polyalcohol copolymer (Vantris(r)).

PMID- 24745538
TI  - Re: delayed-onset ureteral obstruction after endoscopic dextranomer/hyaluronic
      acid copolymer (deflux) injection for treatment of vesicoureteral reflux in
      children: a case series.

PMID- 24745539
TI  - Re: endoscopic correction of VUR using vantris as a new non-biodegradable tissue
      augmenting substance: three years of prospective follow-up.

PMID- 24745541
TI  - Re: lncRNA-dependent mechanisms of androgen-receptor-regulated gene activation
      programs.

PMID- 24745542
TI  - Re: enhanced susceptibility to urinary tract infection in the spinal cord-injured
      host with neurogenic bladder.

PMID- 24745543
TI  - Re: basigin null mutant male mice are sterile and exhibit impaired interactions
      between germ cells and Sertoli cells.

PMID- 24745544
TI  - One moment in time.

PMID- 24745545
TI  - Educating physicians internationally in the diagnosis of child sexual abuse:
      evaluation of a brief educational intervention in Malawi.
AB  - We designed this pilot study to assess physician knowledge and comfort evaluating
      child sexual abuse in Malawi and to evaluate the feasibility of a brief
      educational intervention to improve physician knowledge. A survey was
      administered to 21 physicians before receiving training on child sexual abuse.
      The survey was administered again, 3 days later, to assess improvement. Prior to
      the training, 48% correctly identified the hymen in a photograph, and 24%
      correctly interpreted the photograph as normal. Of the 11 physicians available
      for the posttest 3 days later, significant improvement was found in their ability
      to correctly identify the hymen (6 of 11 pretraining and all 11 posttraining, p =
      0.011) and to interpret the photograph correctly (1 of 11 correct pretraining, 9
      of 11 posttraining, p = 0.001). This study demonstrates the feasibility of
      designing trainings on child sexual abuse in a low-income country. 

PMID- 24745546
TI  - Breaking the silence of child sexual abuse in the Caribbean: a community-based
      action research intervention model.
AB  - In Trinidad and Tobago, little data exists on child sexual abuse, although there
      are many anecdotal reports of high prevalence. The Breaking the Silence Gender
      and Community Empowerment Model is a multidisciplinary intervention to prevent
      and respond to child sexual abuse in Trinidad and Tobago. It is an innovative,
      gender-sensitive intervention that uses a community based action research
      methodology anchored in a national framework. Preliminary evaluation of the
      Breaking the Silence model shows increased knowledge of child sexual abuse,
      increased willingness to discuss child sexual abuse, and an impact that goes
      beyond the target communities. This model can be replicated in communities to
      prevent and respond to child sexual abuse and adapted to address other sensitive
      social issues in the Caribbean. 

PMID- 24745547
TI  - Parental opinions of their child's experience in the legal process: an
      interpretative analysis.
AB  - The aim of this study is to demonstrate how parents of children who are victims
      of sexual assault experience the legal process from the children's and parents'
      perspective. Nine parents, identified in the records of three public prosecution
      offices in three cities in Sweden, were interviewed. The parents described
      feelings of shame and guilt over what their children had experienced. They felt
      stigmatized and had difficulty fulfilling their parental role, perceived a lack
      of information and support from the professionals involved, and experienced a
      sense of withdrawal from their role as parents, though they felt the
      professionals who worked with their children were helpful and influential. 

PMID- 24745548
TI  - Maternal separation attenuates the effect of adolescent social isolation on HPA
      axis responsiveness in adult rats.
AB  - Adverse early life experiences that occur during childhood and adolescence can
      have negative impacts on behavior later in life. The main goal of our work was to
      assess how the association between stressful experiences during neonatal and
      adolescent periods may influence stress responsiveness and brain plasticity in
      adult rats. Stressful experiences included maternal separation and social
      isolation at weaning. Three hours of separation from the pups (3-14 PND)
      significantly increased frequencies of maternal arched-back nursing and licking
      grooming across the first two weeks postpartum. Separation also induced a long
      lasting increase in dams blood levels of corticosterone. Maternal separation did
      not modify brain and plasma allopregnanolone and corticosterone levels in adult
      offspring, but they demonstrate partial recovery from the reduction induced by
      social isolation during adolescence. Moreover, the enhancement of corticosterone
      and allopregnanolone levels induced by foot shock stress in socially isolated
      animals that were subjected to maternal separation was markedly reduced with
      respect to that observed in animals that were just socially isolated. All
      experimental groups showed a significant reduction of BDNF and Arc protein
      expression in the hippocampus. However, the reduction of BDNF observed in animals
      that were maternally separated and subjected to social isolation was less
      significantly pronounced than in animals that were just socially isolated. The
      results sustained the mismatch hypothesis stating that aversive experiences early
      in life trigger adaptive processes, thereby rendering an individual to be better
      adapted to aversive challenges later in life. 

PMID- 24745549
TI  - Production of LYZL6, a novel human c-type lysozyme, in recombinant Pichia
      pastoris employing high cell density fed-batch fermentation.
AB  - Lysozyme acts as an important defensive factor in innate immunity due to its well
      recognized bacteriolytic activity. Here we describe the production and
      performance of human lysozyme-like 6 (LYZL6), a novel human c-type lysozyme
      homolog. A synthetic codon-optimized cDNA encoding the intact amino acid sequence
      of LYZL6 was cloned and expressed in Pichia pastoris SMD1168. Bioactive LYZL6 was
      successfully produced as a single major secreted protein with a molecular weight
      of 15 kDa, and exhibited bacteriolytic activity against Micrococcus
      lysodeikticus. The expression conditions were optimized, and the highest
      expression level of LYZL6 occurred when the recombinant strain was induced with
      1.5% methanol under pH 4.5 at 24 degrees C for 96 h. When high cell density
      fermentation of the recombinant P. pastoris was performed using a fed-batch
      strategy for totally 125 h in a 30 L fermenter, the dry cell weight and the
      extracellular lysozyme activity were increased to 116.3 g/L and 2340 U/mL,
      respectively. The LYZL6 protein concentration was 331 mg/L of fermentation
      supernatant, and the specific activity of LYZL6 towards M. lysodeikticus was 7069
      U/mg. Therefore, we proved that LYZL6 is an antibacterial protein, suggesting a
      potential application of LYZL6 as an antimicrobial agent, and Pichia expression
      system for LYZL6 was successful and industrially promising. 

PMID- 24745550
TI  - Tracked ultrasonography snapshots enhance needle guidance for percutaneous renal
      access: a pilot study.
AB  - BACKGROUND AND PURPOSE: Although ultrasonography-guided percutaneous nephrostomy
      is relatively safe, a number of factors make it challenging for inexperienced
      operators. A computerized needle navigation technique using tracked
      ultrasonography snapshots was investigated to determine whether performance of
      percutaneous nephrostomy by inexperienced users could be improved. METHODS: Ten
      operators performed the procedure on a phantom model with alternating needle
      guidance between conventional ultrasonography and tracked ultrasonography
      snapshots. The needle was reinserted until fluid backflow confirmed calyceal
      access. Needle trajectories were recorded using the real time needle navigation
      system for offline evaluation of operator performance. Recorded needle
      trajectories were used to measure needle motion path length inside the phantom
      tissue, number of reinsertions, total procedure time, and needle insertion time
      as end points of this study. RESULTS: Needle path length measured inside the
      phantom tissue was significantly lower with ultrasonography snapshots guidance
      (295.0+/-23.1 mm, average+/-standard error of the mean) compared with control
      procedures (977.9+/-144.4 mm, P<0.01). This was associated with a significantly
      lower number of needle insertion attempts with ultrasonography snapshots (average
      1.27+/-0.10 vs 2.83+/-0.31, P<0.01). The total procedure time and the needle
      insertion time were also significantly lower with ultrasonography snapshots
      guidance. CONCLUSION: Tracked ultrasonography snapshots appear to improve the
      performance of percutaneous nephrostomy in these preliminary investigations,
      justifying further validation studies. The presented navigation system is
      reproducible because of commercially available hardware and open-source software
      components, facilitating its potential role in clinical practice.

PMID- 24745551
TI  - Effect of pH-responsive alginate/chitosan multilayers coating on delivery
      efficiency, cellular uptake and biodistribution of mesoporous silica
      nanoparticles based nanocarriers.
AB  - Surface fuctionalization plays a crucial role in developing efficient
      nanoparticulate drug-delivery systems by improving their therapeutic efficacy and
      minimizing adverse effects. Here we propose a simple layer-by-layer self-assembly
      technique capable of constructing mesoporous silica nanoparticles (MSNs) into a
      pH-responsive drug delivery system with enhanced efficacy and biocompatibility.
      In this system, biocompatible polyelectrolyte multilayers of alginate/chitosan
      were assembled on MSN's surface to achieve pH-responsive nanocarriers. The
      functionalized MSNs exhibited improved blood compatibility over the bare MSNs in
      terms of low hemolytic and cytotoxic activity against human red blood cells. As a
      proof-of-concept, the anticancer drug doxorubicin (DOX) was loaded into
      nanocarriers to evaluate their use for the pH-responsive drug release both in
      vitro and in vivo. The DOX release from nanocarriers was pH dependent, and the
      release rate was much faster at lower pH than that of at higher pH. The in vitro
      evaluation on HeLa cells showed that the DOX-loaded nanocarriers provided a
      sustained intracellular DOX release and a prolonged DOX accumulation in the
      nucleus, thus resulting in a prolonged therapeutic efficacy. In addition, the
      pharmacokinetic and biodistribution studies in healthy rats showed that DOX
      loaded nanocarriers had longer systemic circulation time and slower plasma
      elimination rate than free DOX. The histological results also revealed that the
      nanocarriers had good tissue compatibility. Thus, the biocompatible multilayers
      functionalized MSNs hold the substantial potential to be further developed as
      effective and safe drug-delivery carriers.

PMID- 24745552
TI  - Antibiotic-free segregational plasmid stabilization in Escherichia coli owing to
      the knockout of triosephosphate isomerase (tpiA).
AB  - BACKGROUND: Segregational stability of plasmids is of major concern for
      recombinant bacterial production strains. One of the best strategies to
      counteract plasmid loss is the use of auxotrophic mutants which are complemented
      with the lacking gene along with the product-relevant ones. However, these
      knockout mutants often show unwanted growth in complex standard media or no
      growth at all under uncomplemented conditions. This led to the choice of a gene
      for knockout that only connects two essential arms of an essential metabolic
      pathway - the glycolysis. RESULTS: Triosephosphate isomerase was chosen because
      its knockout will have a tremendous effect on growth on glucose as well as on
      glycerol. On glycerol the effect is almost absolute whereas on glucose growth is
      still possible, but with considerably lower rate than usual. This feature is
      essential because it may render cloning easier. This enzymatic activity was
      successfully tested as an alternative to antibiotic-based plasmid selection.
      Expression of a model recombinant beta-glucanase in continuous cultivation was
      possible with stable maintenance of the plasmid. In addition, the complementation
      of tpiA knockout strains by the corresponding plasmids and their growth
      characteristics were tested on a series of complex and synthetic media. The
      accumulation of methylglyoxal during the growth of tpiA-deficient strains was
      shown to be a possible cause for the growth disadvantage of these strains in
      comparison to the parent strain for the Keio Collection strain or the
      complemented knock-out strain. CONCLUSION: Through the use of this new
      auxotrophic complementation system, antibiotic-free cloning and selection of
      recombinant plasmid were possible. Continuous cultivation and recombinant protein
      expression with high segregational stability over an extended time period was
      also demonstrated.

PMID- 24745553
TI  - Novel thiazole derivatives: a patent review (2008 - 2012. Part 2).
AB  - INTRODUCTION: Thiazole is a well-known five-membered heterocyclic compound.
      Various methods have been worked out for its synthesis. In the last few decades,
      a lot of work has been done on the thiazole ring to find new drugs with
      antioxidant, analgesic, anti-inflammatory, antimicrobial, antifungal, antiviral,
      diuretic, anticonvulsant, neuroprotective and antitumor or cytotoxic properties
      and fewer side effects. This review presents the up-to-date development of
      different thiazole derivatives. AREAS COVERED: The present review gives an
      account of the recent therapeutic patent literature (2008 - 2012) describing the
      applications of thiazole and its derivatives on selected activities. In this
      review, many relevant biological properties and therapeutic applications of
      thiazole derivatives reported in international patents from all companies have
      been discussed; an overview of the chemical matter has also been given. Because
      of the huge amount of patents registered in this period relative to thiazole
      derivatives, attention has been focused on thiazole derivatives having
      pharmacological activity toward receptors. EXPERT OPINION: Based on the large
      variety of possible therapeutic applications proposed in patents for thiazole
      derivatives having pharmacological activity toward receptors, it is possible to
      point out the unpredictability of pharmacological activity consequent to
      structural modification, more or less simple, of a prototype drug molecule. In
      any case, the thiazole scaffold continues to have great potential in chemical
      pharmaceutical research.

PMID- 24745554
TI  - Latino children's body mass index at 2-3.5 years predicts sympathetic nervous
      system activity at 5 years.
AB  - BACKGROUND: To understand whether the relationship between young children's
      autonomic nervous system (ANS) responses predicted their BMI, or vice versa, the
      association between standardized BMI (zBMI) at 2, 3.5, and 5 years of age and ANS
      reactivity at 3.5-5 years of age, and whether zBMI predicts later ANS reactivity
      or whether early ANS reactivity predicts later zBMI, was studied. METHODS: Low
      income, primarily Latino children (n=112) were part of a larger cohort study of
      mothers recruited during early pregnancy. Study measures included maternal
      prenatal weight, children's health behaviors (i.e., time watching television,
      fast food consumption, and time playing outdoors), children's height and weight
      at 2, 3.5, and 5 years, and children's ANS reactivity at 3.5 and 5 years. ANS
      measures of sympathetic nervous system (i.e., pre-ejection period) and
      parasympathetic nervous system (i.e., respiratory sinus arrhythmia) activity were
      monitored during rest and four challenges. Reactivity was calculated as the
      difference between mean challenge response and rest. Structural equation models
      analyzed the relationship between children's zBMI at 2, 3.5, and 5 years and ANS
      reactivity at 3.5 and 5 years, adjusting for mother's BMI, children's behaviors,
      and changes in height. RESULTS: There was no association between zBMI and ANS
      cross-sectionally. Children with high zBMI at 2 or 3.5 years or large zBMI
      increases from 2 to 3.5 years of age had decreased sympathetic activity at 5
      years. Neither sympathetic nor parasympathetic reactivity at 3.5 years predicted
      later zBMI. CONCLUSIONS: Increased zBMI early in childhood may dampen young
      children's SNS responses later in life.

PMID- 24745555
TI  - An immunocompetent, orthotopic mouse model of epithelial ovarian cancer utilizing
      tissue engineered tumor cell sheets.
AB  - Despite the development of a myriad of anticancer drugs that appeared promising
      in preclinical ovarian cancer animal models, they failed to predict efficacy in
      clinical testing. To improve the accuracy of preclinical testing of efficacy and
      toxicity, including pharmacokinetic and pharmacodynamic evaluations, a novel
      animal model was developed and characterized. In this study, murine ID8
      (epithelial ovarian cancer [EOC]) cells as injected cell suspensions (ICS) and as
      intact cultured monolayer cell sheets (CS) were injected or surgically grafted,
      respectively, into the left ovarian bursa of 6-8 week-old, female C57BL/6 black
      mice and evaluated at 8 and 12 weeks after engraftment. Tumor volumes at 8 weeks
      were as follows: 30.712 +/- 18.800 mm(3) versus 55.837 +/- 10.711 mm(3) for ICS
      and CS, respectively, p = 0.0990 (n = 5). At 12 weeks, tumor volumes were 128.129
      +/- 44.018 mm(3) versus 283.953 +/- 71.676 mm(3) for ICS and CS, respectively, p
      = 0.0112 (n = 5). The ovarian weights at 8 and 12 weeks were 0.02138 +/- 0.01038
      g versus 0.04954 +/- 0.00667 g for ICS and CS, respectively (8 weeks), p =
      0.00602 (n = 5); and 0.10594 +/- 0.03043 g versus 0.39264 +/- 0.09271 g for ICS
      and CS, respectively (12 weeks), p = 0.0008 (n = 5). These results confirm a
      significant accelerated tumorigenesis in CS-derived tumors compared with ICS
      derived tumors when measured by tumor volume/time and ovarian weight/time.
      Furthermore, the CS-derived tumors closely replicated the metastatic spread found
      in human EOC and histopathological identity with the primary tumor of origin.

PMID- 24745556
TI  - PBDEs and PBBs in human serum and breast milk from cohabiting UK couples.
AB  - Concentrations of PBDEs and PBBs were measured in matched blood and breast milk
      samples from 10 UK couples collected in 2011-12. These data are the first
      measurements in human serum from the UK since the 2004 EU ban on all uses of the
      penta-and octa-BDE formulations and the 2008 ban on the use of the deca-BDE
      formulation in some applications. Serum ?PBDE tri-hepta concentrations ranging
      from 1.0 to 16 ng g(-1) lipid weight, with median 4.0 ng g(-1) lw were measured.
      Breast milk ?PBDE tri-hepta concentrations ranged from 1.3 to 21 ng g(-1) lw,
      with median 5.7 ng g(-1) lw. Couples had similar serum congener concentrations
      unless one of them frequently stayed away from home for work (different diet and
      dust exposures) or one had occupational exposure to foams and furnishings or
      electronics. BB-153 were measured above LOD in 40% of sera and 100% of breast
      milks samples, with median concentrations of 0.04 and 0.06, and maximums of 0.91
      and 0.79 ng g(-1) lw respectively. Concentrations in this study indicated a
      modest decrease from pre-ban levels reported for the UK. BDE-209 was detected
      above the limit of detection (LOD) in 15% of sera and 83% of breast milks, with
      ranges <1.2-20 and <0.2-1.0 ng g(-1) lw respectively. Average daily infant
      intakes were estimated at 17, 5, 5 and 3 ng kg(-1) bw for BDE-47,-99,-153 and 
      209 respectively, all well below relevant US-EPA threshold reference dose values
      (RfDs).

PMID- 24745557
TI  - Brominated flame retardant exposure of aircraft personnel.
AB  - The use of brominated flame retardants (BFRs) such as polybrominated diphenyl
      ethers (PBDEs) in aircraft is the result of high fire safety demands. Personnel
      working in or with aircraft might therefore be exposed to several BFRs. Previous
      studies have reported PBDE exposure in flight attendants and in passengers. One
      other group that may be subjected to significant BFR exposure via inhalation, are
      the aircraft maintenance workers. Personnel exposure both during flights and
      maintenance of aircraft, are investigated in the present study. Several BFRs were
      present in air and dust sampled during both the exposure scenarios; PBDEs,
      hexabromocyclododecane (HBCDD), decabromodiphenyl ethane (DBDPE) and 1,2-bis
      (2,4,6-tribromophenoxy) ethane. PBDEs were also analyzed in serum from
      pilots/cabin crew, maintenance workers and from a control group of individuals
      without any occupational aircraft exposure. Significantly higher concentrations
      of PBDEs were found in maintenance workers compared to pilots/cabin crew and
      control subjects with median total PBDE concentrations of 19, 6.8 and 6.6 pmol g(
      1) lipids, respectively. Pilots and cabin crew had similar concentrations of most
      PBDEs as the control group, except for BDE-153 and BDE-154 which were
      significantly higher. Results indicate higher concentrations among some of the
      pilots compared to the cabin crew. It is however, evident that the cabin
      personnel have lower BFR exposures compared to maintenance workers that are
      exposed to such a degree that their blood levels are significantly different from
      the control group.

PMID- 24745558
TI  - Commercially available chemicals as immunizing haptens for the development of a
      polyclonal antibody recognizing carbendazim and other benzimidazole-type
      fungicides.
AB  - Carbendazim is a fungicide widely used for controlling fungi affecting fruits,
      vegetables, field crops etc. Determination of carbendazim in water, soil and
      various crops is frequently required to assure compliance with national/European
      regulations. A polyclonal antibody recognizing carbendazim was developed by using
      commercially available 2-(2-aminoethyl) benzimidazole, 2-benzimidazole propionic
      acid and 2-mercaptobenzimidazole as immunizing haptens; each of the above
      derivatives was directly conjugated to the carrier protein keyhole limpet
      hemocyanin and a mixture of the conjugates was administered to New Zealand white
      rabbits. Immunochemical functionality of the antisera and the corresponding
      isolated antibody (whole IgG fraction) was evaluated through titer and
      displacement curves in an in-house developed ELISA, which employed a 2
      mercaptobenzimidazole - functionalized lysine-dendrimer as the immobilized
      hapten. As shown with ELISA-displacement curves, the above antibody could
      recognize carbendazim as well as other benzimidazole-type fungicides, i.e.
      benomyl and thiabendazole, and also intact benzimidazole, while it did not cross
      react with the structurally different pesticides carbaryl and imazalil.
      Considering the rather simple approach which has led to its development and its
      highly promising immunochemical profile, the new antibody may be exploited in
      immunoanalytical systems for detecting benzimidazole-type pesticides e.g. in
      samples of environmental interest. The above antibody is being currently tested
      as a biorecognition element in the novel FOODSCAN cell biosensor platform for
      pesticide residue detection based on the Bioelectric Recognition Assay
      technology. 

PMID- 24745559
TI  - Comparison of UVC/S2O8(2-) with UVC/H2O2 in terms of efficiency and cost for the
      removal of micropollutants from groundwater.
AB  - This study compared the UVC/S2O8(2-) system with the more commonly used AOP in
      water industry, UVC/H2O2, and examined whether the first one can be an
      economically feasible alternative technology. Atrazine and 4 volatile compounds
      (methyl tert-butyl ether, cis-dichlorethen, 1,4-dioxane and 1,1,1
      trichloroethane) were chosen as model contaminants because they exhibit different
      susceptibility to UVC photolysis and AOPs. A collimated beam apparatus was
      utilized for the majority of the experiments (controlled environment, without
      mass transfer phenomena), while selected experiments were performed in a flow
      through reactor to simulate industrial applications. Initial experiments on the
      activation of oxidants with a LP lamp indicated that S2O8(2-) is photolysed about
      2.3 times faster than H2O2 and that the applied treatment times were not
      sufficient to utilize the majority of the oxidant. The effect of oxidants'
      concentrations were tested with atrazine alone and in the micropollutants'
      mixture and it was decided to use 11.8 mg L(-1) S2O8(2-) and 14.9 mg L(-1) H2O2
      for further testing since is closer to industrial applications and to minimize
      the residual oxidant concentration. Changes of the matrix composition of the
      treated water were investigated with the addition of chloride, bicarbonate and
      humic acids at concentrations relevant to a well-water-sample, the results showed
      that the system least affected was UVC/H2O2. Only when bicarbonate was used,
      UVC/S2O8(2-) performed better. Overall, testing these systems with the mixture of
      micropollutants gave better insights to their efficiency than atrazine alone and
      UVC/S2O8(2-) is recommended for selective oxidation of challenging matrices.

PMID- 24745560
TI  - Factors associated with fear of falling and associated activity restriction in
      community-dwelling older adults: a systematic review.
AB  - OBJECTIVE: Fear of falling (FOF) is an important threat to autonomy. Current
      interventions to reduce FOF have yielded conflicting results. A possible reason
      for this discrepancy could be its multicausality. Some risk factors may not have
      been identified and addressed in recent studies. The last systematic review
      included studies until 2006. METHODS: To identify additional risk factors for FOF
      and to test those mentioned previously, we conducted a systematic literature
      review. Studies examining FOF in community-dwelling older adults between 2006 and
      October 2013 were screened. RESULTS: Outcomes are summarized with respect to
      different constructs such as FOF, fall-related self-efficacy/balance confidence,
      and FOF-related activity restriction. Odds ratios and p values are reported.
      There is no clear pattern with regard to the different FOF-related constructs
      studied. The only parameters robustly associated across all constructs were
      female gender, performance-based and questionnaire-based physical function, the
      use of a walking aid, and, less robust, a history of falls and poor self-rated
      health. Conflicting results were identified for depression and anxiety, multiple
      drugs, and psychotropic drugs. Other potentially modifiable risk factors were
      only mentioned in one or two studies and warrant further investigation.
      Parameters with mainly negative results are also presented. CONCLUSION: Only few
      risk factors identified were robustly associated across all FOF-related
      constructs and should be included in future studies on FOF. Some newer factors
      have to be tested again in different cohorts. The comprehensive overview might
      assist in the conceptualization of future studies.

PMID- 24745561
TI  - Anxiety is not associated with the risk of dementia or cognitive decline: the
      Rotterdam Study.
AB  - OBJECTIVE: Anxiety and depression frequently co-occur in the elderly and in
      patients with dementia. Prior research has shown that depression is related to
      the risk of dementia, but the effect of anxiety on dementia remains unclear. We
      studied whether anxiety symptoms and anxiety disorders are associated with the
      risk of dementia and cognition. METHODS: We studied 2,708 nondemented
      participants from the prospective, population-based Rotterdam Study who underwent
      the Hospital Anxiety and Depression Scale (HADS) (sample I, baseline 1993-1995)
      and 3,069 nondemented participants who underwent screening for anxiety disorders
      (sample II, baseline 2002-2004). In 1993-1995, anxiety symptoms were assessed
      using the HADS. In 2002-2004, anxiety disorders were assessed using the
      Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition. In both
      study samples, participants were continuously monitored for dementia until
      January 1, 2011. Cognition was tested in 2002-2004 and at a follow-up visit in
      2009-2011 in sample II only. RESULTS: In sample I, 358 persons developed
      dementia, and in sample II, 248 persons developed dementia. We did not find an
      association with the risk of dementia for anxiety symptoms (hazard ratio 1.05,
      95% confidence interval: 0.77-1.43, Wald statistic 0.08, p = 0.77, df = 1) or for
      anxiety disorders (hazard ratio 0.92, 95% confidence interval: 0.58-1.45, Wald
      statistic 0.14, p = 0.71, df = 1). We could demonstrate an association of anxiety
      disorders with poor cognition cross-sectionally, but this attenuated after
      additional adjustments. CONCLUSION: Our findings do not offer evidence for an
      association between anxiety symptoms or anxiety disorders with the risk of
      dementia or with cognition. This suggests that anxiety is not a risk factor nor a
      prodrome of dementia in an elderly, community-dwelling population.

PMID- 24745563
TI  - Perceived discrimination and physical, cognitive, and emotional health in older
      adulthood.
AB  - OBJECTIVE: To examine whether perceived discrimination based on multiple personal
      characteristics is associated with physical, emotional, and cognitive health
      concurrently, prospectively, and with change in health over time among older
      adults. DESIGN: Longitudinal. SETTING: Health and Retirement Study (HRS).
      PARTICIPANTS: Participants (N = 7,622) who completed the Leave-Behind
      Questionnaire as part of the 2006 HRS assessment (mean age 67 years);
      participants (N = 6,450) completed the same health measures again in 2010.
      MEASUREMENTS: Participants rated their everyday experience with discrimination
      and attributed those experiences to eight personal characteristics: race,
      ancestry, sex, age, weight, physical disability, appearance, and sexual
      orientation. At both the 2006 and 2010 assessments, participants completed
      measures of physical health (subjective health, disease burden), emotional health
      (life satisfaction, loneliness), and cognitive health (memory, mental status).
      RESULTS: Discrimination based on age, weight, physical disability, and appearance
      was associated with poor subjective health, greater disease burden, lower life
      satisfaction, and greater loneliness at both assessments and with declines in
      health across the four years. Discrimination based on race, ancestry, sex, and
      sexual orientation was associated with greater loneliness at both time points,
      but not with change over time. Discrimination was mostly unrelated to cognitive
      health. CONCLUSIONS: The detrimental effect of discrimination on physical and
      emotional health is not limited to young adulthood but continues to contribute to
      health and well-being in old age. These effects were driven primarily by
      discrimination based on personal characteristics that change over time (e.g.,
      age, weight) rather than discrimination based on more stable characteristics
      (e.g., race, sex).

PMID- 24745564
TI  - Rapid, high-frequency, and theta-coupled gamma oscillations in the inferior
      occipital gyrus during face processing.
AB  - Neuroimaging studies have found greater activation in the inferior occipital
      gyrus (IOG), or occipital face area, in response to faces relative to non-facial
      stimuli. However, the temporal, frequency, and functional profiles of IOG
      activity during face processing remain unclear. Here, this issue was investigated
      by recording intracranial field potentials in the IOG during the presentation of
      faces, mosaics, and houses in upright and inverted orientations. Time-frequency
      statistical parametric mapping analyses revealed greater gamma-band activation in
      the IOG beginning at 110 msec and covering 40-300 Hz in response to upright faces
      relative to upright houses and mosaics. Phase-amplitude cross-frequency coupling
      analyses revealed more evident theta-gamma couplings at 115-256 msec during the
      processing of upright faces as compared with that of upright houses and mosaics.
      Comparable gamma-band activity was observed during the processing of inverted and
      upright faces at about 100-200 msec, but weaker activity and different coupling
      with theta-band activity after 200 msec. These patterns of activity were more
      evident in the right than in the left IOG. These results, together with other
      evidence on neural communication, suggest that broadband gamma oscillations in
      the right IOG conduct rapid and multistage (i.e., both featural and configural)
      face processing in collaboration with theta oscillations transmitted from other
      brain regions.

PMID- 24745562
TI  - Delirium diagnosis methodology used in research: a survey-based study.
AB  - OBJECTIVE: To describe methodology used to diagnose delirium in research studies
      evaluating delirium detection tools. METHODS: The authors used a survey to
      address reference rater methodology for delirium diagnosis, including rater
      characteristics, sources of patient information, and diagnostic process,
      completed via web or telephone interview according to respondent preference.
      Participants were authors of 39 studies included in three recent systematic
      reviews of delirium detection instruments in hospitalized patients. RESULTS:
      Authors from 85% (N = 33) of the 39 eligible studies responded to the survey. The
      median number of raters per study was 2.5 (interquartile range: 2-3); 79% were
      physicians. The raters' median duration of clinical experience with delirium
      diagnosis was 7 years (interquartile range: 4-10), with 5% having no prior
      clinical experience. Inter-rater reliability was evaluated in 70% of studies.
      Cognitive tests and delirium detection tools were used in the delirium reference
      rating process in 61% (N = 21) and 45% (N = 15) of studies, respectively, with
      33% (N = 11) using both and 27% (N = 9) using neither. When patients were too
      drowsy or declined to participate in delirium evaluation, 70% of studies (N = 23)
      used all available information for delirium diagnosis, whereas 15% excluded such
      patients. CONCLUSION: Significant variability exists in reference standard
      methods for delirium diagnosis in published research. Increasing standardization
      by documenting inter-rater reliability, using standardized cognitive and delirium
      detection tools, incorporating diagnostic expert consensus panels, and using all
      available information in patients declining or unable to participate with formal
      testing may help advance delirium research by increasing consistency of case
      detection and improving generalizability of research results.

PMID- 24745565
TI  - Increased risk of incisional hernia after sigmoid colectomy for diverticulitis
      compared with colon cancer.
AB  - BACKGROUND: We aimed to determine if an increased incidence of incisional hernias
      is present in patients undergoing sigmoidectomy for diverticulitis vs cancer. The
      pathophysiology of diverticulitis is poorly understood, but might involve a
      collagen vascular abnormality that can predispose to incisional hernia. STUDY
      DESIGN: In this IRB-approved, retrospective study, patients who underwent sigmoid
      colectomies for diverticulitis or cancer between January 2003 and September 2012
      were studied. Exclusion criteria included the development of surgical site
      infections and neoadjuvant chemoradiotherapy. A multivariate logistic regression
      was used with covariate adjustments for known risk factors for hernia
      development. RESULTS: Four hundred forty-two patients (mean age 59.3 +/- 13.9
      years) with a median follow-up of 30 months were analyzed. The incidence of
      incisional hernia was 15.1% in diverticulitis patients vs 5.8% in the cancer
      cohort (41 of 271 vs 10 of 171; p = 0.003). Univariate analysis of risk factors
      associated with postoperative incisional hernia included steroid use (p = 0.007),
      wound packing (p = 0.001), higher American Society of Anesthesiologists
      classification (p = 0.001), absorbable suture closure (p = 0.02), blood
      transfusion (p = 0.04), stoma formation (p = 0.02), increased body mass index (p
      = 0.008), and history of incisional hernia (p = 0.00008). Multivariate logistic
      regression demonstrated a persistent association between diverticulitis and
      hernia development (p = 0.01). Odds of a hernia developing after sigmoidectomy
      for diverticulitis were 2.82 times greater than in the cancer cohort (95% CI, 1.3
      6.6). CONCLUSIONS: The incidence of an incisional hernia developing after a
      sigmoid colectomy is significantly higher when performed for diverticulitis as
      compared with cancer. This might be due to a connective tissue disorder, which
      predisposes to development of both diverticula and hernias.

PMID- 24745566
TI  - Management of anastomotic leakage in a nationwide cohort of colonic cancer
      patients.
AB  - BACKGROUND: The mortality associated with anastomotic leakage (AL) after colonic
      cancer surgery is high and management often results in permanent fecal diversion.
      Preservation of bowel continuity in combination with proximal loop diversion
      (salvage) may reduce the number of permanent ostomies without jeopardizing
      safety. STUDY DESIGN: This nationwide study used prospective data from the
      database of the Danish Colorectal Cancer Group, the National Patient Registry,
      and patient files. Patients with AL requiring surgery (grade C) were categorized
      according to the type of surgical treatment as anastomotic takedown with an end
      ostomy or salvage. Thirty-day mortality, long-term mortality, and permanent
      ostomy rates were analyzed using multivariable logistic and Cox regression
      analyses. RESULTS: Anastomotic leakage occurred in 593 of 9,333 patients (6.4%),
      of whom 507 with grade C were included. Takedown and salvage were undertaken in
      433 (85.4%) and 74 (14.6%) patients, respectively. Salvage was performed more
      frequently for Hinchey I-II or minor anastomotic defects and resulted in
      increased likelihood of stoma reversal (adjusted hazard ratio 3.24, 95% CI 2.04
      to 5.16, p < 0.001), corresponding to a risk of permanent fecal diversion of
      16.8%, compared with 54.5% after takedown. Adjusted mortality rates were
      comparable between the groups. A second episode of AL after stoma reversal
      occurred more frequently in patients with end-ileostomies (10 of 64) than in
      patients with end-colostomies (1 of 64) or loop-ileostomies (3 of 36), p = 0.017.
      CONCLUSIONS: Patients with Hinchey I-II and small anastomotic defect were safely
      managed by anastomotic salvage, which reduced the risk of permanent fecal
      diversion. Anastomotic salvage is a viable option for this subset of patients.

PMID- 24745567
TI  - Pediatric inpatient humanitarian care in combat: Iraq and Afghanistan 2002 to
      2012.
AB  - BACKGROUND: The purpose of this study was to define the scope of combat- and
      noncombat-related inpatient pediatric humanitarian care provided from 2002 to
      2012 by the United States (US) Military in Iraq and Afghanistan. STUDY DESIGN: A
      review of the Patient Administration Systems and Biostatistics Activity (PASBA)
      database for all admissions from 2002 to 2012 by US military hospitals in
      Afghanistan and Iraq for children 14 years of age and younger provided data to
      analyze the use of medical care. North Atlantic Treaty Organization
      Standardization Agreement (STANAG) injury codes provided injury cause and the ICD
      codes provided diagnosis. In-hospital mortality, blood usage, number of invasive
      procedures, and hospital stay were analyzed by country and injury category.
      RESULTS: There were 6,273 admissions that met inclusion criteria. In Afghanistan,
      there were more than twice as many pediatric noncombat-related admissions (2,197)
      as pediatric combat-related admissions (1,095). In Iraq, the difference was
      minimal (1,391 noncombat vs 1,590 combat). The most common cause of noncombat
      related admission in both countries was injury: primarily motor vehicle related
      and burns, which varied significantly by age. Older patients (older than 8 years
      in Afghanistan and older than 4 years in Iraq) were more likely combat victims.
      Mortality was highest for combat trauma in Iraq (11%) and noncombat trauma in
      Afghanistan (8%). The in-hospital mortality in both countries was 5% for
      admissions unrelated to trauma. Resource use was highest for combat trauma in
      both countries. CONCLUSIONS: Noncombat-related medical care was the primary
      reason for pediatric humanitarian admissions to United States military combat
      hospitals in Iraq and Afghanistan from 2002 to 2012. Combat-related injuries have
      a higher mortality than noncombat injuries or other admissions.

PMID- 24745568
TI  - Systematic review on the patient-reported outcomes of tissue-expander/implant vs
      autologous abdominal tissue breast reconstruction in postmastectomy breast cancer
      patients.

PMID- 24745569
TI  - The Affordable Care Act and academic surgery: expectations and possibilities.

PMID- 24745570
TI  - Identification tags for associating liver partition and portal vein ligation for
      staged hepatectomy: a critical appraisal of an "original" technical proposal.

PMID- 24745571
TI  - Early detection of potentially severe acute pancreatitis.

PMID- 24745572
TI  - Reply: To PMID 24355874.

PMID- 24745573
TI  - Ventral hernia risk score: the importance of patient selection and technique.

PMID- 24745574
TI  - Reply: To PMID 24051068.

PMID- 24745575
TI  - Transcystic access cannot be a good choice for bile leakage test after major
      liver resections.

PMID- 24745576
TI  - Reply: air leak test, two hands are better than none.

PMID- 24745577
TI  - Optimizing prosthetic technique for ventral hernia repair.

PMID- 24745578
TI  - Reply: To PMID 24083910.

PMID- 24745579
TI  - Mesh prophylaxis to prevent parastomal hernia.

PMID- 24745581
TI  - Application of continuous negative pressure irrigation and negative pressure
      fixation to treat a bronchopleural fistula with thoracic empyema.

PMID- 24745582
TI  - Medial open transversus abdominal plane catheter analgesia: a simple, safe,
      effective technique after open liver resection.

PMID- 24745583
TI  - Microtia in the Netherlands: clinical characteristics and associated anomalies.
AB  - BACKGROUND: In Europe there have been few detailed reports on the clinical
      characteristics of microtia patient populations. The objective of the present
      study is to contribute to our insight of microtia in Europe by examining the
      Dutch microtia population treated in the University Medical Center Utrecht (UMCU)
      with regards to its clinical features and associated anomalies. In addition, an
      overview of the literature is provided for thorough comparison. METHODS: A
      retrospective chart review was performed for all microtia patients referred to
      the UMCU for reconstructive surgery of the auricle over the period 1990-2012.
      Previous studies were identified by a systematic search of the electronic
      literature databases PubMed and Embase. In a subsequent meta-analysis the results
      from the literature review were pooled by geographical region to facilitate
      comparison. RESULTS: A total of 204 microtia patients were referred for
      reconstructive surgery during 1990-2012. This group was characterized by a male
      predominance of 60.8%. Unilateral disease was observed in 91.7% of patients,
      affecting the right auricle in 66.3%. In unilateral patients lobule type microtia
      was seen in 59.9%, (small) concha type in 34.4% and anotia in 5.7%. The more
      frequent anomalies associated with microtia were atresia of the acoustic meatus
      (76.0%), preauricular skin tags (30.5%), hemifacial microsomia (27.5%), facial
      nerve paralysis (8.3%) and congenital heart disease (2.5%). Familial occurrence
      of microtia was reported for 2.0% of UMCU patients and for 10.0% of patients in
      the literature. CONCLUSION: The clinical characteristics of microtia in the
      Netherlands correspond to those reported for other patient populations in the
      literature. Most congenital anomalies associated with microtia in Dutch patients
      belong to the Oculo-Auriculo-Vertebral Spectrum. The considerable degree of
      familial microtia observed in the literature points to a substantial genetic
      component in the etiology of the condition.

PMID- 24745584
TI  - Trans-oral endoscopic cerclage pharyngoplasty for treatment of velopharyngeal
      insufficiency.
AB  - OBJECTIVES: Velopharyngeal insufficiency (VPI) is a common problem after cleft
      palate repair, it leads to speech distortion with consequent affection of speech
      intelligibility. Many techniques have been used in the treatment of VPI with
      varying results and complications. The aim of this study was to evaluate the
      efficacy of trans-oral endoscopic cerclage pharyngoplasty in the treatment of
      VPI. METHODS: Eighteen patients with hypernasality after palatoplasty were
      subjected to trans-oral endoscopic cerclage pharyngoplasty. Pre and postoperative
      evaluation of velopharyngeal function were performed by using auditory perceptual
      assessment, nasometric assessment, and flexible nasopharyngoscopy. RESULTS:
      Significant postoperative improvement of speech parameters measured with auditory
      perceptual assessment were achieved, and the overall postoperative nasalance
      score was improved significantly for nasal and oral sentences. Also, flexible
      nasopharyngoscopy showed significant improvement of velopharyngeal closure. No
      marked postoperative complications were reported apart from throat pain and
      dysphagia that disappeared with time. CONCLUSIONS: Trans-oral endoscopic cerclage
      pharyngoplasty is an effective method for the treatment of VPI.

PMID- 24745585
TI  - Long-term evaluation and clinical outcomes of children with dental transplants in
      Temuco city, Chile.
AB  - AIM: To assess the clinical and radiographic outcomes of 36 transplanted teeth
      and the possible factors affecting the results. MATERIALS AND METHODS: In 26
      children, 36 teeth transplants were performed. The main reason for
      transplantations was the loss of anterior teeth due to trauma; 80.5% of
      transplanted teeth were immature bicuspids. The transplants were clinically and
      radiolographycally monitored in respect of pulp vitality, root canal
      obliteration, periradicular changes and root formation. Fisher Exact Test and
      Kaplan-Meier analyses were performed to determine the association between the
      variables and estimation of survival rates, respectively. RESULTS: Thirty (83.3%)
      of the transplantations were recorded as successful and six as unsuccessful
      (16.7%). The survival rate was 97.2% during average time of 47.5 months +/- 27.8
      SD. Only one tooth had been extracted and 5 had survived in not ideal conditions.
      The majority of immature transplanted teeth developed pulp canal obliteration.
      CONCLUSION: Factors associated to successful outcome were immature root formation
      of donor tooth and short flexible splinting period. The main factor associated to
      failure was replacement resorption. The surgical technique did not present
      statistical significance in the clinical outcome. Tooth transplantation has shown
      high success and survival rates, and should be considered as a real option in
      growing patients.

PMID- 24745586
TI  - Occurrence of oral trauma in young epileptic patients.
AB  - AIM: People with reduced efficiency, as well as those who experience seizures,
      are prone to traumatic injuries within the facial skeleton. This study aimed to
      evaluate the incidence of traumatic injuries of the oral cavity in epileptic
      children and youths from special-care schools. MATERIALS AND METHODS: The study
      was carried out in children and youths with intellectual disability attending
      special-care schools in the city of Poznan (Poland). The study group comprised 63
      epileptic students (31 female and 32 male), aged 6-20 years. Information on
      disease prevalence was obtained from medical records. The control group consisted
      of 63 students (23 female and 40 male), aged 7-20 years, not suffering from
      epilepsy, randomly selected from individuals in the same schools. The examination
      included assessment of dental traumatic injuries (crown fracture or traumatic
      tooth loss). STATISTICS: For statistical analysis relating to differences in the
      occurrence of injuries of teeth between epileptic subjects and control group, the
      chi- square test was used, but in case of a low number of observations, chi
      square with Yates's correction. RESULTS: Crown's fracture of permanent teeth was
      reported in 10 subjects (15.9% of all patients), which involved 13 permanent
      incisors. Tooth loss as a result of the injury was seen only in one 14-year-old
      subject. However, in the control group, symptoms of crown's fracture were found
      in six permanent teeth in 4 patients (6.4% of all subjects). CONCLUSION: It is
      necessary to provide appropriate dental care to epileptic patients because of the
      risk of injuries and the need for a special prosthodontic rehabilitation.

PMID- 24745587
TI  - Traumatic dental injuries in children. Experience of a hospital in the central
      Anatolia region of Turkey.
AB  - AIM: The purpose of this retrospective study was to identify traumatic dental
      injuries by using the documentations of children (range 0-14 years, average age:
      10.79+/-2.06) with dental trauma who referred to Cumhuriyet University, Faculty
      of Dentistry, Department of Pedodontics, in Sivas, Turkey, between January 2007
      and June 2012. MATERIALS AND METHODS: A total of 591 children (356 boys and 235
      girls) with 1,287 injured teeth (394 primary and 893 permanent teeth) were
      included in the study. The children were evaluated in terms of gender, age,
      number of injured teeth, type of trauma, the interval between the traumatic event
      and time of seeking, and treatment procedures. RESULTS: The highest frequency of
      trauma occurred in the 12-14 year age group (14%). The most common type of injury
      was enamel-dentin fractures (58%) in primary teeth and complicated crown
      fractures (39%) in permanent teeth. Falls (30%) were the major cause of dental
      injury. Direct restoration (27%) without any endodontic treatment was the most
      common treatment procedure for permanent teeth. The most frequent treatment for
      primary teeth was examination and follow-up (42%). The upper central incisors
      (71%) were the mostly affected teeth in both primary and permanent teeth. Most
      dental trauma occurred in June and July (12%-8%). Only 63 children (11%) were
      referred to the clinic less than 30 minutes after trauma. CONCLUSION: Traumatic
      dental injury is considered a serious public health problems especially in
      children; parents and teachers should be informed on prevention and emergency
      management of traumatic dental injuries. In addition, the findings showed that
      initial treatment after dental trauma should be as quick as possible.

PMID- 24745588
TI  - Treatment of traumatic dental injuries: evaluation of knowledge among Italian
      dentists.
AB  - AIM: The aim of this study was to evaluate the degree of knowledge in the
      management of different scenarios of dental trauma in a population of Italian
      dentists. MATERIALS AND METHODS: A closed-ended questionnaire consisting of 5
      clinical cases of common traumatic dental injuries was asked to be filled out by
      dentists in the area of Milan, Italy. A total of 500 questionnaires were
      collected; after a descriptive analysis of the population, results of correct
      answers were expressed in frequency distribution and computed in percentages. To
      examine possible associations between the level of knowledge for each question
      (number/percentage of correct answers) and independent variables of the
      population (sex, number of years after graduation, attendance of dental trauma
      courses, type of clinical activity) appropriate correlation tests were performed
      (Pearson chi-square, or Fisher's exact; level of significance = 0.05) for
      identification of statistically significant differences. RESULTS: More than 75%
      of participants answered correctly to the questions regarding crown fracture and
      extrusive luxation injuries; only 40% of dentists responded correctly about the
      duration and type of splinting following avulsion; 60% of participants
      incorrectly chose immediate invasive therapies (tooth extraction or endodontic
      procedures) for horizontal middle-root fracture. There was a trend towards
      slightly better knowledge (in 7 out of 9 questions) for dentists 1) working in
      hospitals and 2) who had attended a post-graduate course in traumatology.
      CONCLUSION: The level of knowledge in the group of dentists considered was
      heterogeneous; problems in the management of traumatic dental injuries were
      restricted to specific clinical cases and topics.

PMID- 24745589
TI  - A long-term retrospective clinical study on MTA pulpotomies in immature permanent
      incisors with complicated crown fractures.
AB  - AIM: The study was undertaken to evaluate mineral trioxide aggregate (MTA)
      clinically and radiographically as a pulpotomy agent in immature permanent teeth
      whose pulps were exposed by a complicated crown fracture. MATERIALS AND METHODS:
      Thirty incisors with exposed pulps in twenty-nine patients were examined for this
      retrospective study. According to exclusion criteria, only twenty-seven teeth
      were selected. Each tooth was treated with partial pulpotomy and the wounded pulp
      was covered with mineral trioxide aggregate. The children were recalled for
      clinical and radiographic evaluation at 3 months, 6 months, at approximately 12
      months and 36 months. RESULTS: Out of 27 cases, 22 were categorized as 'healed'
      and 1 as 'healing'. The remaining 4 ones highlighted persistent disease and
      needed further endodontic treatment. CONCLUSION: MTA partial pulpotomy is an
      effective treatment in maintaining pulpal vitality and allowing physiological
      root development (apexogenesis).

PMID- 24745590
TI  - Renal excretion of fluoride after fluoride mouth rinses in children.
AB  - AIM: This study was conducted to determine if there was an increase in the
      urinary excretion of fluoride, after the use of fluoride mouth rinses in
      children. MATERIALS AND METHODS: The sample consisted of 58 children aged 5-8
      years, randomly selected, residents in non-fluoridated water areas. Urine samples
      were collected prior to mouthwash and also 2 hours after use. The control sample,
      which received no treatment, consisted of 16 children of equivalent age and from
      the same community. Urinary excretion of fluoride was analysed by determining the
      pH, creatinine, F- ion and fluoride (mg)/creatinine (g) (F/Cr) ratio in urine.
      Results In the studied sample, the mean F/Cr ratio before fluoride mouth rinse
      was 0.26 mg/g and it rose to 1.58 mg/g 2 hours after mouth rinse. This difference
      of 1.33 mg/g was statistically highly significant (p<.001). In the control group
      no significant changes occurred. The average 2 hours afterward F/Cr ratios were
      0.29 and 0.27 respectively (p=0.426). CONCLUSION: After the use of a fluoride
      mouthwash, in children, there is a statistically significant increase of fluoride
      ion in urine, which can be attributed to the application of this product.

PMID- 24745591
TI  - Clinical safety, quality and effect of resin infiltration for proximal caries.
AB  - AIM: Resin infiltration of proximal lesions is a new approach to stop caries
      progression. The aim of this clinical trial was to assess its safety and quality,
      as well as the therapeutic effect. MATERIALS AND METHODS: In 47 children,
      adolescents and young adults, ten dentists applied the infiltration material ICON
      (DMG, Germany) on initial proximal lesions according to the manufacturer's
      instruction. One lesion with radiographic extension into enamel or the outer
      third of dentin per participant was allocated for the treatment. The clinical
      safety and quality of resin infiltration were assessed 1 week, 6 months and 12
      months after the treatment and the evaluation of the therapeutic effect was
      analysed by pair-wise radiographs. RESULTS: The clinical safety and quality of
      the infiltration were assessed in 45 individuals after 12 months. The test
      surfaces showed no relevant changes in clinical status, plaque accumulation or
      gingival status (p > 0.05). A high quality of infiltration was found for the
      marginal adaptation. In contrast to the improvement of colour at the one-week
      recall (p = 0.005), the infiltrated surfaces showed a statistically significant
      increase in the discoloration within the following year (p = 0.014). Out of the
      43 lesions which could be assessed radiographically, only two lesions showed
      progression to a different score (4.7%). CONCLUSION: Resin infiltration can be
      considered a safe and effective treatment to reduce progression of initial
      proximal caries.

PMID- 24745592
TI  - Oral health and dental late adverse effects in children in remission from
      malignant disease. A pilot case-control study in Italian children.
AB  - AIM: To investigate with a reliable method the oral features in Italian patients
      in remission from cancer, highlighting the relationship with age at cancer
      therapy and to compare the data with healthy controls. MATERIALS AND METHODS:
      Twenty five childhood cancer survivors treated under the age of 10 years with
      chemotherapy w/wo Haemopoietic Stem Cell Transplantation and/or head-neck
      Radiotherapy, in remission from cancer for at least 3 years, were examined for
      dental caries and enamel defects. To assess dental age and dental abnormalities a
      panoramic radiograph was taken. Patients were grouped according to age at cancer
      therapy (<3 years: subgroup Y; 3.1-5 years: subgroup M; >5 years: subgroup O). A
      control group of 26 healthy children was included. RESULTS: There was not a
      statistically significant difference in caries prevalence between the two groups.
      A statistically significant difference between the two groups was found for
      enamel defects, dental abnormalities and dental age. The chi-squared test
      revealed a relationship between age at therapy and specific dental abnormalities.
      CONCLUSION: This study shows that cancer therapy may increase the risk of
      development of enamel defects and dental abnormalities, especially in children
      treated under the age of 3 years.

PMID- 24745593
TI  - Correlation between unstimulated salivary flow, pH and streptococcus mutans,
      analysed with real time PCR, in caries-free and caries-active children.
AB  - AIM: Evaluate the correlations between unstimulated salivary flow, pH and level
      of S. mutans, analysed through real time PCR, in caries-free and caries-active
      children. MATERIALS AND METHODS: Thirty healthy children were divided into 2
      groups: test group (DMFT/dmft >= 3 and at least 1 active caries lesion) and
      control group (DMFT/dmft=0). Un-stimulated saliva was collected, pH was measured
      and S. mutans and total bacterial amount were evaluated with real-time PCR
      analysis. RESULTS: Unstimulated salivary flow in the test group was significantly
      lower (p = 0.0269) compared to group control. The level of S. mutans was higher
      in the test group (p = 0.176), and an inverse correlation was recorded between
      total bacterial amount and un-stimulated salivary flow (p = 0.063). In the
      control group a positive relationship was found between total bacterial amount
      and S. mutans (p = 0.045) and an inverse correlation between pH and S. mutans (p
      = 0.088). A t-test and a linear regression analysis were performed. CONCLUSION: A
      higher salivary flow and an increased salivary pH seem to represent protective
      factors against caries in children, while high levels of S. mutans are correlated
      with caries active lesions. Caries risk assessment should be performed
      considering all parameters involved in the development of the disease.

PMID- 24745594
TI  - The Italian perspective on fluoride intake in children and adolescents.
AB  - AIM: This paper represents the outcome of the meetings of the Committee composed
      by Pedodontists (SIOI - Italian Society of Paediatric Dentistry) and
      Paediatricians (FIMP - Italian Association of Paediatricians) with the aim to
      share an evidence- based common approach in caries prevention during childhood
      and adolescence. The most important topic was an update on fluoride
      administration methods in order to minimise the risk of fluorosis and maximise
      its caries-preventive effect. CONCLUSION: The conclusions of this work are
      exposed in a synoptic table.

PMID- 24745595
TI  - Dento-skeletal effects of mixed palatal expansion evaluated by postero-anterior
      cephalometric analysis.
AB  - AIM: The aim of this study was to evaluate the dento-skeletal effects of mixed
      palatal expansion (MPE) on growing patients with a uni- or bilateral posterior
      crossbite and mild-to-moderate crowding as compared to untreated growing
      individuals using postero- anterior (PA) cephalometric analysis. MATERIALS AND
      METHODS: A group of 24 patients (18 girls and 6 boys) treated with a Hyrax- type
      device was compared to an untreated matched control group at T0 (8.6 yrs +/-
      2.01) and T1 (10 yrs +/- 2.00) using PA cephalograms. The cephalometric analysis
      included eight bilateral skeletal and dental landmarks. The groups were compared
      using independent sample t-test to estimate dento-skeletal effects on PA
      cephalograms. RESULTS: The treated group showed significant changes for the
      maxillary width (P<0.001) and upper molar width (P<0.001) when compared to those
      of the control group. CONCLUSION: MPE may effectively increase transverse
      dimensions and correct posterior crossbites.

PMID- 24745596
TI  - Temporomandibular joint involvement in a cohort of patients with Juvenile
      Idiopatic Arthritis and evaluation of the effect induced by functional
      orthodontic appliance: clinical and radiographic investigation.
AB  - AIM: The aim of the study was to assess possible correlations between the
      clinical parameters of temporomandibular joint (TMJ) arthritis and pathologic MRI
      findings of the TMJ in patients affected by juvenile idiopathic arthritis (JIA),
      and the effect of a functional orthodontic therapy on the evolution of TMJ
      disorders. MATERIALS AND METHODS: A prospective clinical and nuclear magnetic
      resonance (NMR) investigation was conducted on a sample of 53 patients (41
      female, 12 male) with JIA, treated for 24 months with an Andresen appliance. The
      involvement of TMJ was defined by clinical and radiological signs. NMR
      assessments were performed in closed and maximum opening mouth position before
      (T0) and at the end of functional orthodontic therapy (T1). RESULTS: Fifteen
      patients showed physical and radiologic TMJ abnormalities. Changes were not
      uniformly distributed among the different JIA subtypes. Patients with
      poliarticular JIA (>=5 peripheral joints affected) showed more destructive bony
      changes. No correlation existed between clinical symptoms and NMR alterations.
      Approximately one half of the patients experienced significant improvement of the
      TMJ and muscular pain using the Andresen appliance. CONCLUSION: The prevalence of
      TMJ involvement in patients suffering of JIA, and the improvement of TMJ and
      muscular pain associated with the use of functional appliance found in the
      present study, suggest an alert for TMJ dysfunction in patients with JIA and
      demonstrate the utility of functional orthodontic therapy in preventing the
      morbidities associated with TMJ arthritis in JIA.

PMID- 24745597
TI  - The impact of rapid palatal expansion on children's general health: a literature
      review.
AB  - AIM: The original indication for rapid palatal expansion was to treat skeletal
      maxillary constriction. As positive effects were clinically proven, the number of
      indications for rapid palatal expansion has continuously grown. The purpose of
      the present article was to review the literature and to evaluate the effect of
      rapid palatal expansion on nose breathing, natural head position, obstructive
      sleep apnoea syndrome, nocturnal enuresis and conductive hearing loss.
      CONCLUSION: It can be concluded that rapid palatal expansion is predominantly
      recommended in children with maxillary constriction. In those with normal
      occlusion, maxillary expansion can be considered as the really last choice of
      treatment when other treatment options in patients with nose breathing,
      obstructive sleep apnea syndrome (OSAS), nocturnal enuresis and conductive
      hearing loss (CHL) have failed. Therefore, collaboration between paediatricians,
      otolaryngologists, paediatric dentists and orthodontists will lead to the best
      treatment outcomes in the future.

PMID- 24745598
TI  - Second Class Resolver: a retrospective analysis.
AB  - AIM: To evaluate the use of Second Class Resolver (SCR), a new fixed orthopaedic
      appliance, for the treatment of skeletal Class II malocclusion in growing
      subjects. MATERIALS AND METHODS: Design Retrospective analysis. Forty subjects
      were treated with Second Class Resolver (SCR). The mean age was 8 years at the
      beginning of treatment and 10 years at the end of treatment. Digital
      cephalometric superimpositions on lateral radiographs taken at start and end of
      treatment were assessed. The cephalometric values were statistically analysed.
      RESULTS: Cephalometric analysis of changes during treatment shows reduction of
      ANB angle (mean 2 degrees ); reduction of Witts Index (mean 3 mm); reduction of
      Maxillo-Mandibular angle (MM) (mean 1 degrees ); reduction of SNA (angle mean 3
      degrees ); reduction of gonial angle (mean 1.8 degrees ); increase of the
      mandibular branch length (mean 5 mm); increase of mandibular body (mean 2.9
      degrees ). CONCLUSION: The Second Class Resolver can be beneficially used for the
      treatment of Class II malocclusion.

PMID- 24745599
TI  - Substantial bone loss in the mandibular central incisors area as a complication
      of tongue piercing: a case report.
AB  - BACKGROUND: Along with the increasing popularity of oral piercings, the number of
      reported complications and side effects increases, too. CASE REPORT: The aim of
      this report is to present a case of substantial bone loss in the area of the
      mandibular central incisors caused by lingual piercing and persistent bad habits.
      Dentist should be aware of potential complications associated with oral piercings
      and warn patients about them.

PMID- 24745600
TI  - Vitamin K intake and mortality in people with chronic kidney disease from NHANES
      III.
AB  - BACKGROUND & AIMS: Cardiovascular disease (CVD) is the leading cause of death in
      patients with chronic kidney disease (CKD), partly due to increased vascular
      calcification. Vitamin K plays a role in preventing vascular calcification in CKD
      yet the relationship between vitamin K intake and mortality in CKD patients
      remains unclear. METHODS: This observational cohort study included 3401
      participants with CKD from the Third National Health and Nutrition Examination
      Survey. Vitamin K intake was estimated from 24-h dietary recalls (1988-94).
      Mortality was determined from the National Death Index records through 2006. Cox
      proportional hazards regression was used to estimate Hazard Ratios (HR) by
      comparing those with adequate intake of vitamin K to those with low intake,
      adjusting for advanced CKD covariates. For sensitivity analysis, these
      associations were also examined among those with different renal status. RESULTS:
      During a median follow-up of 13.3 years (37,408 person-years), 1815 and 876
      participants died from all-cause and CVD causes, respectively. 72% of the
      participants had vitamin K intake lower than the recommended adequate intake.
      Participants with vitamin K intake higher than recommended adequate intake for
      vitamin K were associated with lower risk of all-cause (HR = 0.85; 95%: 0.72-1; P
      = 0.047) and CVD mortality (HR = 0.78; 95%: 0.64-95; P = 0.016). Sensitivity
      analyses in subgroups with advanced CKD revealed similar findings. CONCLUSIONS:
      This observational study suggests that adequate intake of vitamin K may be
      associated with reduced all-cause and CVD mortality in CKD patients. However,
      vitamin K may be a marker of a healthy diet; therefore clinical trials may help
      in clarifying the effect of vitamin K independent of a healthy diet.

PMID- 24745602
TI  - Electrochemical detection of insulating beads at subattomolar concentration via
      magnetic enrichment in a microfluidic device.
AB  - We report electrochemical detection of collisions between individual magnetic
      microbeads, present at subattomolar concentrations, and electrode surfaces. This
      limit of detection is 4 orders of magnitude lower than has been reported
      previously, and it is enabled by using a magnetic field to preconcentrate the
      microbeads prior to detection in a microfluidic electrochemical cell.
      Importantly, the frequency of collisions between the microbeads and the electrode
      is not compromised by the low concentration of microbeads. These findings
      represent an unusual case of detecting individual electrochemical events at very
      low analyte concentration. In addition to experiments supporting these claims,
      finite-element simulations provide additional insights into the nature of the
      interactions between flowing microbeads and their influence on electrochemical
      processes. 

PMID- 24745601
TI  - Smoking at time of diagnosis and breast cancer-specific survival: new findings
      and systematic review with meta-analysis.
AB  - INTRODUCTION: In women with breast cancer who smoke, it is unclear whether
      smoking could impair their survival from the disease. METHODS: We examined the
      relation of smoking at diagnosis to breast cancer-specific and overall survival
      among 5,892 women with invasive breast cancer treated in one Canadian center
      (1987 to 2008). Women were classified as never, former or current smokers.
      Current smokers were further classified according to total, intensity and
      duration of smoking. Deaths were identified through linkage to population
      mortality data. Cox proportional-hazards multivariate models were used. A
      systematic review with meta-analysis combines new findings with published
      results. RESULTS: Compared with never smokers, current smokers at diagnosis had a
      slightly, but not statistically significant, higher breast cancer-specific
      mortality (hazard ratio = 1.15, 95% confidence interval (CI): 0.97 to 1.37).
      Among current smokers, breast cancer-specific mortality increased with total
      exposure to, intensity and duration of smoking (all Ptrend <0.05). Compared to
      never smokers, breast cancer-specific mortality was 32 to 56% higher among heavy
      smokers (more than 30 pack years of smoking, more than 20 cigarettes per day or
      more than 30 years of smoking). Smoking at diagnosis was associated with an
      increased all-cause mortality rate. A meta-analysis of all studies showed a
      statistically significant, 33% increased mortality from breast cancer in women
      with breast cancer who are smokers at diagnosis compared to never smokers (hazard
      ratio = 1.33, 95% CI: 1.12 to 1.58). CONCLUSIONS: Available evidence to date
      indicates that smoking at diagnosis is associated with a reduction of both
      overall and breast cancer-specific survival. Studies of the effect of smoking
      cessation after diagnosis on breast cancer-specific outcomes are needed.

PMID- 24745603
TI  - Dynamic characteristics of the rotor in a magnetically suspended control moment
      gyroscope with active magnetic bearing and passive magnetic bearing.
AB  - For a magnetically suspended control moment gyroscope, stiffness and damping of
      magnetic bearing will influence modal frequency of a rotor. In this paper the
      relationship between modal frequency and stiffness and damping has been
      investigated. The mathematic calculation model of axial passive magnetic bearing
      (PMB) stiffness is developed. And PID control based on internal model control is
      introduced into control of radial active magnetic bearing (AMB), considering the
      radial coupling of axial PMB, a mathematic calculation model of stiffness and
      damping of radial AMB is established. According to modal analysis, the
      relationship between modal frequency and modal shapes is achieved. Radial
      vibration frequency is mainly influenced by stiffness of radial AMB; however,
      when stiffness increases, radial vibration will disappear and a high frequency
      bending modal will appear. Stiffness of axial PMB mainly affects the axial
      vibration mode, which will turn into high-order bending modal. Axial PMB causes
      bigger influence on torsion modal of the rotor. 

PMID- 24745604
TI  - Synthesis of 3D-nanonet hollow structured Co3O4 for high capacity supercapacitor.
AB  - A 3D-nanonet structured cobalt-basic-carbonate precursor has been obtained by a
      facile, low cost and eco-friendly route under ambient temperature and pressure.
      After calcination in air, the as-prepared precursor was converted to a 3D-nanonet
      hollow structured Co3O4 with its original frame structure almost preserved.
      Encouragingly, by alternating experimental parameters (Table S1 in the Supporting
      Information ), such as concentration of the starting reagents and calcination
      temperature, we got the optimized condition for the final product with desirable
      electrochemical performance (Figure S1 in the Supporting Information ). The
      pseudocapacitive properties of the obtained Co3O4 were evaluated by cyclic
      voltammetry (CV), galvanostatic charge-discharge measurement and electrochemical
      impedance spectroscopy in 6.0 M KOH solution. At different scan rates of 5, 10,
      20, and 30 mV s(-1), the corresponding specific capacitances were 820, 755, 693,
      and 656 F g(-1), respectively. The material also exhibited superior charge
      discharge stability and maintained 90.2% of its initial capacitance after 1000
      continuous charge-discharge cycles at a current density of 5 A g(-1). From a
      broad view, our research and the outstanding results not only present a feasible
      access to nanostructured Co3O4 but also remind us of paying more attention to the
      simple synthetic methods without complex processes and sophisticated instruments.

PMID- 24745605
TI  - Biochemical and functional characterization of Plasmodium falciparum GTP
      cyclohydrolase I.
AB  - BACKGROUND: Antifolates are currently in clinical use for malaria preventive
      therapy and treatment. The drugs kill the parasites by targeting the enzymes in
      the de novo folate pathway. The use of antifolates has now been limited by the
      spread of drug-resistant mutations. GTP cyclohydrolase I (GCH1) is the first and
      the rate-limiting enzyme in the folate pathway. The amplification of the gch1
      gene found in certain Plasmodium falciparum isolates can cause antifolate
      resistance and influence the course of antifolate resistance evolution. These
      findings showed the importance of P. falciparum GCH1 in drug resistance
      intervention. However, little is known about P. falciparum GCH1 in terms of
      kinetic parameters and functional assays, precluding the opportunity to obtain
      the key information on its catalytic reaction and to eventually develop this
      enzyme as a drug target. METHODS: Plasmodium falciparum GCH1 was cloned and
      expressed in bacteria. Enzymatic activity was determined by the measurement of
      fluorescent converted neopterin with assay validation by using mutant and GTP
      analogue. The genetic complementation study was performed in ?folE bacteria to
      functionally identify the residues and domains of P. falciparum GCH1 required for
      its enzymatic activity. Plasmodial GCH1 sequences were aligned and structurally
      modeled to reveal conserved catalytic residues. RESULTS: Kinetic parameters and
      optimal conditions for enzymatic reactions were determined by the fluorescence
      based assay. The inhibitor test against P. falciparum GCH1 is now possible as
      indicated by the inhibitory effect by 8-oxo-GTP. Genetic complementation was
      proven to be a convenient method to study the function of P. falciparum GCH1. A
      series of domain truncations revealed that the conserved core domain of GCH1 is
      responsible for its enzymatic activity. Homology modelling fits P. falciparum
      GCH1 into the classic Tunnelling-fold structure with well-conserved catalytic
      residues at the active site. CONCLUSIONS: Functional assays for P. falciparum
      GCH1 based on enzymatic activity and genetic complementation were successfully
      developed. The assays in combination with a homology model characterized the
      enzymatic activity of P. falciparum GCH1 and the importance of its key amino acid
      residues. The potential to use the assay for inhibitor screening was validated by
      8-oxo-GTP, a known GTP analogue inhibitor.

PMID- 24745606
TI  - Diamide insecticide target site specificity in the Heliothis and Musca ryanodine
      receptors relative to toxicity.
AB  - Anthranilic and phthalic diamides act on the ryanodine receptor (RyR), which
      constitutes the Ca(2+)-activated Ca(2+) channel and can be assayed as shown here
      in Heliothis thoracic muscle tissue with anthranilic diamide
      [(3)H]chlorantraniliprole ([(3)H]Chlo), phthalic diamide [(3)H]flubendiamide
      ([(3)H]Flu), and [(3)H]ryanodine ([(3)H]Ry). Using Heliothis with [(3)H]Chlo or
      [(3)H]Flu gives very similar anthranilic and phthalic diamide binding site
      structure-activity correlations, indicating a common binding site. The
      anthranilic and phthalic diamide stimulation of [(3)H]Ry binding in Heliothis
      generally parallels their inhibition of [(3)H]Chlo and [(3)H]Flu binding. In
      Musca adults [(3)H]Ry binding site stimulation is a good predictor of in vivo
      activity for anthranilic but not phthalic diamides, and no high-affinity
      [(3)H]Flu specific binding site is observed. These relationships establish
      species differences in diamide target site specificity important in structure
      optimization and target site-based resistance mechanisms. 

PMID- 24745607
TI  - Efficacy and safety of local steroids for urethra strictures: a systematic review
      and meta-analysis.
AB  - INTRODUCTION: Local steroids have been used as an adjuvant therapy to patients
      undergoing internal urethrotomy (IU) in treating urethral strictures. Whether
      this technique is effective and safe is still controversial. The aim of this
      study is to determine the efficacy and safety of local steroids as applied with
      the IU procedure. METHODS: A systematic review of the literature was performed by
      searching Medline, Embase, Cochrane Library Databases, and the Web of Science. We
      included only prospective randomized, controlled trials that compared the
      efficacy and safety between IU procedures with applied local steroids and those
      without. RESULTS: Eight studies were found eligible for further analysis. In
      total, 203 patients undergoing IU were treated with steroid injection or catheter
      lubrication. Time to recurrence is statistically significant (mean: 10.14 and
      5.07 months, P<0.00001).The number of patients with recurrent stricture formation
      significantly decreased at different follow-up time points (P=0.05).No
      statistically significant differences were found between the recurrence rates,
      adverse effects, and success rates of second IUs in patients with applied local
      steroids and those without. CONCLUSION: The use of local steroids with IU seems
      to prolong time to stricture recurrence but does not seem to affect the high
      stricture recurrence rate following IU. When local steroids are applied with
      complementary intention, the disease control outcomes are encouraging. Further
      robust comparative effectiveness studies are now required.

PMID- 24745608
TI  - Analysis of health consumers' behavior using self-tracker for activity, sleep,
      and diet.
AB  - BACKGROUND: With the ever-increasing availability of health information
      technology (HIT) enabling health consumers to measure, store, and manage their
      health data (e.g., self-tracking devices), more people are logging and managing
      their own health data for the purpose of promoting general well-being. To develop
      and implement effective and efficient strategies for improving personal
      monitoring devices, a rigorous theoretical framework to explain the health
      consumer's attitude, intention, and behavior needs to be established. The aim of
      this study is to verify the HIT acceptance model (HITAM) in the context of the
      health consumer's attitude, behavioral intention, and behavior of utilizing self
      trackers. Furthermore, the study aims to gain better understanding of self
      tracking behavior in the context of logging daily activity level, sleep patterns,
      and dietary habits. SUBJECTS AND METHODS: Forty-four female college students were
      selected as voluntary study participants. They used self-trackers for activity,
      sleep, and diet monitoring for 90 or more consecutive days. The logged data were
      analyzed and fitted to the HITAM to verify whether the model was suitable for
      capturing the various behavioral and intention-related characteristics observed.
      RESULTS: The overall fitness indices for the HITAM using the field data yielded
      an acceptable fitness to the model, with all path coefficients being
      statistically significant. The model accounts for 66.8% of the variance in
      perceived usefulness, 43.9% of the variance in perceived ease of use, 83.1% of
      the variance in attitude, and 48.4% of the variance in behavioral intention. The
      compliance ranking of self-tracking behavior, in order of decreasing compliance,
      was activity, sleep, and diet. This ranking was consistent with that of ease of
      use of the personal monitoring device used in the study. CONCLUSIONS: The HITAM
      was verified for its ability to describe the health consumer's attitude,
      behavioral intention, and behavior. The analysis indicated that the ease of use
      of a particular HIT device stands as the most significant barrier in the way of
      increasing the efficacy of self-tracking.

PMID- 24745609
TI  - Metastasis of hepatocellular carcinoma to the scapula.

PMID- 24745610
TI  - Apoptosis-inducing effects of Melissa officinalis L. essential oil in
      glioblastoma multiforme cells.
AB  - Current therapies for glioblastoma multiforme (GBM) are not effective. This study
      investigated the activity of the M. officinalis essential oil (EO) and its major
      component (citral) in GBM cell lines. Both EO and citral decreased the viability
      and induced apoptosis of GBM cells as demonstrated by DNA fragmentation and
      caspase-3 activation. Antioxidant prevented citral-induced death, indicating its
      dependence on the production of reactive oxygen species. Citral downmodulated the
      activity and inhibited the expression of multidrug resistance associated protein
      1 (MRP1). These results show that EO, through its major component, citral, may be
      of potential interest for the treatment of GBM.

PMID- 24745611
TI  - Identification of novel predictive markers for the prognosis of pancreatic ductal
      adenocarcinoma.
AB  - This study demonstrated that klotho gene expression was significantly lower
      whereas miR-504 and phospho-IGF-1R levels were significantly higher in PDAC than
      in normal pancreatic tissues. miR-504 level significantly correlated with klotho
      mRNA and promoter methylation level in PDACs. Loss of Klotho protein expression,
      klotho promoter hypermethylation, high miR-504 levels, and high phospho-IGF-1R
      levels significantly correlated with poor survival, high clinical and
      pathological stages in PDAC patients. The demethylation reagent and miR-504
      inhibitor increased klotho gene expression, invasion, and migration in BxPC-3 and
      Panc-1 cells. Klotho is a tumor suppressor whose expression in PDAC correlated
      with progression and prognosis of PDAC.

PMID- 24745612
TI  - Biological effects of (125)i seeds radiation on A549 lung cancer cells: G2/M
      arrest and enhanced cell death.
AB  - External beam radiation (EBRT) and (125)I seeds continuous low dose rate
      radiation (CLDR) were used to treat patients with lung cancer. We herein
      investigated the biological effects of EBRT and CLDR on lung cancer cells. A549
      human lung cancer cell line was thus exposed to different doses of EBRT and CLDR.
      CLDR was more efficient to inhibit cell growth than EBRT. CLDR induced increased
      DNA damage as evidenced by long-lasting p-H2AX activity. The enhanced inhibitory
      effects of CLDR on lung cancer cell growth may be, at least in part, due to the
      increased Bax/Bcl2 ratio and cyclin B1-mediated G2/M arrest.

PMID- 24745613
TI  - Prognostic impact of microRNA-145 down-regulation in adult T-cell
      leukemia/lymphoma.
AB  - Adult T-cell leukemia/lymphoma (ATL) is a highly aggressive tumor caused by human
      T-cell leukemia virus type 1. MicroRNAs (miRNAs) are closely involved in the
      development and progression of various tumors. Here we investigated the
      dysregulation of miRNAs in ATL and its clinical significance. Studies using miRNA
      arrays and subsequent real-time reverse transcription polymerase chain reaction
      showed that, in the 9 ATL cell lines examined, 1 miRNA was consistently up
      regulated, whereas another 3 were consistently down-regulated, compared with
      normal CD4-positive lymphocytes. Next, we analyzed the prognostic impact of these
      4 miRNAs in patients with aggressive-type ATL (n = 40). Of the 4 dysregulated
      miRNAs selected, 3 (miR-130b higher expression, miR-145 lower expression, and miR
      223 lower expression) were significantly associated with a worsened overall
      patient survival. We found that expressions of these 3 miRNAs were correlated
      with each other. To clarify which of the 3 had the most significant impact on
      overall survival, we performed a multivariate prognostic analysis that included
      these 3 miRNAs, and only miR-145 lower expression was selected as an independent
      risk factor (P = .0005). When overexpressed in an ATL cell line in vitro, miR-145
      specifically inhibited tumor cell growth. In conclusion, our study suggests that
      miR-145 down-regulation provides a growth advantage in ATL and is highly
      associated with a worsened prognosis for patients with ALT. Hence, miR-145 may be
      a useful prognostic marker and a potential therapeutic target for ATL. 

PMID- 24745614
TI  - Cell size as a prognostic factor in oncocytic poorly differentiated carcinomas of
      the thyroid.
AB  - Histological and cytological criteria in predicting clinical outcomes in patients
      with oncocytic poorly differentiated carcinoma (PDC) of the thyroid were
      investigated. In a set of 102 PDC patients, we performed a computer-assisted
      evaluation of cell size based on two different methods. Univariate analysis
      showed that cell size was a discriminant prognostic parameter in oncocytic PDC
      (30 cases) but not in the non-oncocytic carcinoma cases (72 cases). Patients with
      oncocytic PDC with small-medium cell size had a significantly increased risk of
      death (P = .029) and a decrease of disease-free survival (P = .014). This
      correlation was absent in cases of non-oncocytic PDC, where age and extensive
      vascular invasion were significant indicators of progression. The proposed
      morphological signature shows a robust discriminatory ability when tested on the
      oncocytic PDC group, and cell size assessment could thus be proposed as an
      inexpensive and readily evaluable parameter for predicting prognosis and planning
      therapy in this tumor type. 

PMID- 24745615
TI  - Pathology residency training: time for a new paradigm.
AB  - The exponential growth of the field of pathology over the past several decades
      has created challenges for residency training programs. These challenges include
      the ability to train competent pathologists in 4 years, an increased demand for
      fellowship training, and the structuring and completion of maintenance of
      certification. The authors feel that pathology residency training has reached a
      critical point and that a new paradigm for training is required. 

PMID- 24745616
TI  - Differential expression of GATA-3 in urothelial carcinoma variants.
AB  - GATA binding protein 3 (GATA-3) is a novel immunohistochemical marker for
      urothelial carcinoma (UC); however, few studies have investigated GATA-3's role
      as a marker for UC variants. We used immunohistochemistry to assess GATA-3
      expression in different UC variants, including micropapillary (n = 46),
      sarcomatoid (n = 43), small cell carcinoma (n = 22), and plasmacytoid (n = 16)
      variants, and we also compared GATA-3 expression in conventional bladder UC (n =
      103) to that in squamous cell carcinoma (n = 14). GATA-3 expression was present
      in 70% (72/103) of conventional bladder UCs and highly concordant between matched
      primary and metastatic UCs. The GATA-3 expression levels of the micropapillary
      variants (57%; 26/46) and plasmacytoid variants (44%; 7/16) were not
      significantly different from that of conventional UC. However, the GATA-3
      expression levels of the sarcomatoid variants (16%; 7/43) and small cell
      carcinoma variants (5%; 1/22), which only weakly expressed the protein, were
      significantly lower than that of conventional UC (P < .001). Only 7% of squamous
      cell carcinomas (1/14) expressed GATA-3, and it was also significantly lower than
      that of conventional UC (P < .001). GATA-3 expression was not significantly
      associated with tumor stage or patients' clinical outcomes. In conclusion, GATA-3
      expression differed among UC variants. GATA-3 is a useful marker for confirming
      the urothelial origin of micropapillary and plasmacytoid UC variants but not that
      of sarcomatoid or small cell carcinoma variants. GATA-3 can also be used in
      differentiating UC from squamous cell carcinoma. 

PMID- 24745617
TI  - A testing algorithm for detection of the B-type Raf kinase V600E mutation in
      papillary thyroid carcinoma.
AB  - The B-type Raf kinase (BRAF) V600E mutation is a useful diagnostic marker for
      papillary thyroid carcinoma (PTC). We developed a testing algorithm for the BRAF
      mutation using BRAF immunohistochemistry (IHC) in PTC. Formalin-fixed, paraffin
      embedded PTC tissues from 91 patients were immunostained with a BRAF V600E
      mutation-specific antibody. The immunostaining results were interpreted
      semiquantitatively by adding the scores of the proportion of positive cells
      (scored 0 to 5) and staining intensity (score 0 to 3). To validate BRAF IHC, 4
      molecular methods were used: direct sequencing, pyrosequencing, peptide nucleic
      acid clamping polymerase chain reaction, and real-time polymerase chain reaction.
      The cut-off score of BRAF IHC for predicting the BRAF mutation was 5.5. In 68
      cases, where the BRAF IHC score was 6 or more, 89.7% were positive for the BRAF
      mutation by 2 or more molecular methods and 97.1% by one or more methods. In 13
      cases, where the IHC score was between 4 or more and less than 6, 61.5% were
      positive for the BRAF mutation by 2 or more methods and 69.2% by at least one
      method. In 10 cases, where the IHC score was less than 4, BRAF mutation was noted
      in one case only by one molecular method. BRAF V600E IHC scores of less than 4 or
      6 or more should not require confirmation by additional tests. However, BRAF
      V600E IHC scores of 4 or 5 may require confirmation of the BRAF V600E mutation.
      In addition, BRAF IHC scores 6 or more were more sensitive than any single
      molecular method; therefore, BRAF IHC may overcome the limitations of using a
      single type of molecular method. 

PMID- 24745618
TI  - Insulin-like growth factor 1 pathway mutations and protein expression in resected
      non-small cell lung cancer.
AB  - The purpose of this study was to characterize the prevalence of insulin-like
      growth factor 1 receptor (IGF1R) mutations, single nucleotide polymorphisms
      (SNP), and protein overexpression in surgically resected non-small cell lung
      cancers in relation to patient characteristics and prognosis. This retrospective
      study was conducted on 304 patients with non-small cell lung cancers who
      underwent curative pulmonary resection (median follow-up for surviving patients,
      3.6 years). IGF1R gene alterations (n = 304) and protein expression (n = 181)
      were evaluated by polymerase chain reaction-based assays and
      immunohistochemistry, respectively. Membranous and cytoplasmic staining were
      analyzed separately. In an exploratory analysis, 1 silent mutation in exon 16 and
      3 mutations in introns of the IGF1R gene comprising the tyrosine kinase domain
      were detected. Moreover, evaluating selected IGF1R SNPs, patients with
      adenocarcinomas and homozygous for the rs8038415 T-allele had a significantly
      better survival (P = .025) but no different disease-free survival. Regarding
      expression, membranous but not cytoplasmic IGF1R staining was higher in squamous
      cell carcinomas versus other histologies (P < .0001) and showed a trend to longer
      survival (P = .08). No association between SNP variations and protein expression
      was found. Membranous IGF1R protein expression is higher in squamous cell versus
      other histologies but does not correlate with prognosis. SNPs and mutations can
      be detected and may harbor prognostic value. These alterations may be of interest
      when evaluating the IGF1R as potential therapeutic target and should receive
      further research. 

PMID- 24745619
TI  - IMP3 expression is associated with poor outcome and epigenetic deregulation in
      intrahepatic cholangiocarcinoma.
AB  - IMP3 is a fetal protein not expressed in normal adult tissues. IMP3 is an
      oncoprotein and a useful biomarker for a variety of malignancies and is
      associated with reduced overall survival of a number of them. IMP3 expression and
      its prognostic value for patients with intrahepatic cholangiocarcinoma (ICC) have
      not been well investigated. The molecular mechanism underlying IMP3 expression in
      human cancer cells remains to be elucidated. Here we investigated IMP3 expression
      in ICC and adjacent nonneoplastic liver in 72 unifocal primary ICCs from a single
      institute by immunohistochemistry, immunoblotting, and real-time polymerase chain
      reaction. IMP3 was specifically expressed in cancer cells but not in the
      surrounding normal tissue, and 59 (82%) of 72 ICCs were IMP3 positive by
      immunohistochemistry. Among 35 cases with lymphovascular invasion, 26 (74%)
      showed IMP3 positivity in lymph node metastases. IMP3 expression was
      significantly correlated with tumor size, pathological grade, metastasis, and
      clinical stage. Kaplan-Meier analysis demonstrated an inverse correlation between
      IMP3 expression and overall survival rate. Multivariate analysis revealed that
      IMP3 was the only risk factor associated with survival. To further explore the
      mechanism of IMP3 expression in cancers, we identified 2 CpG islands at IMP3
      proximal promoter. Interestingly, the IMP3 promoter was almost completely
      demethylated in ICCs in contrast to densely methylated promoter in normal liver
      tissues. IMP3 expression is a useful biomarker for ICCs and can provide an
      independent prognostic value for patients with ICC. To our knoweldge, this is the
      first direct evidence of epigenetic deregulation of IMP3 in human cancer. 

PMID- 24745620
TI  - A NSQIP risk assessment for thyroid surgery based on comorbidities.
AB  - BACKGROUND: Thyroid surgery is associated with low mortality and morbidity and
      often is performed in an ambulatory setting. The majority of patients undergoing
      thyroidectomy have an uncomplicated outcome, but common comorbidities may
      increase mortality and morbidity. Due to low complication rates, studies using
      single surgeon or single institutional data to identify risk factors for adverse
      outcomes may be limited by inadequate patient volume. STUDY DESIGN: This
      retrospective cohort study used data from the American College of Surgeons
      National Surgical Quality Improvement Program (ACS NSQIP). The study group
      included all thyroidectomy patients over a 6-year period (2005 to 2010). Common
      patient comorbidities were identified and analyzed using logistic regression.
      Risk of adverse outcomes was calculated for single and multiple comorbidities.
      Statistical significance was set at p < 0.05. RESULTS: The study group included
      38,577 consecutive patients. Thirty-day mortality and postoperative morbidity
      were 0.06% and 1.49%, respectively. The risk factors independently associated
      with morbidity included hypertension, diabetes, advanced age greater than 70
      years, COPD, dialysis, malignant thyroid disease, and surgical approach (total
      thyroidectomy). Substernal thyroidectomy, hypertension, diabetes, age greater
      than 70 years, COPD, and dialysis were significant predictors (unadjusted) of
      mortality. Multiple comorbidities resulted in significant cumulative risk. The
      presence of 3 or more comorbidities was associated with a postoperative morbidity
      of 5.1% (p < 0.001) and mortality as high as 12.5%. CONCLUSIONS: Thyroid surgery
      is generally safe. Common comorbidities significantly increase the risk of
      adverse outcomes and death. Clinically applicable risk calculation based on
      overall health may improve patient selection, surgical management, and informed
      consent.

PMID- 24745621
TI  - Voice outcomes after total thyroidectomy, partial thyroidectomy, or non-neck
      surgery using a prospective multifactorial assessment.
AB  - BACKGROUND: Voice alteration remains a significant complication of thyroid
      surgery. We present a comparison of voice outcomes between total thyroidectomy
      (TT), partial thyroidectomy (PT), and non-neck (NN) surgery using a
      multifactorial voice-outcomes classification tool. STUDY DESIGN: Patients with
      normal voice (n = 112) were enrolled between July 2004 and March 2009. The
      patients underwent TT (n = 54), PT (n = 35), or NN (n = 23) surgery under general
      endotracheal anesthesia as part of a prospective observational study involving
      serial multimodality voice evaluation preoperatively, and at 2 weeks, 3 months,
      and 6 months postoperatively. Patients with adverse voice outcomes were grouped
      into the negative voice outcomes (NegVO) category, including patients with
      objective (abnormality on videolaryngostroboscopy and substantial voice
      dysfunction) and subjective (normal videolaryngostroboscopy but with notable
      voice impairment) NegVO. Voice outcomes were compared among study groups.
      RESULTS: Negative voice outcomes occurred in 46% (95% CI, 34-59%) and 14% (95%
      CI, 6-30%) of TT and PT groups, respectively. No NegVOs were observed after NN
      surgery. Early NegVOs were more common in the TT group than in the NN or PT
      groups (p < 0.001). Most voice disturbances resolved by 6 months (TT 84%; PT 92%)
      with no difference in NegVO among all groups (p = 0.23). Black race and
      significant changes in certain voice outcomes measures at the 2-week follow-up
      visit were identified as predictors of late (3 to 6 months) NegVO. CONCLUSIONS:
      This comprehensive voice outcomes study revealed that the extent of thyroidectomy
      impacts voice outcomes in the early postoperative period, and identified risk
      factors for late NegVO in post-thyroidectomy patients who should be considered
      for early voice rehabilitation referral.

PMID- 24745622
TI  - A three-year prospective study of repeat head computed tomography in patients
      with traumatic brain injury.
AB  - BACKGROUND: A definitive consensus on the standardization of practice of a
      routine repeat head CT (RHCT) scan in patients with traumatic intracranial
      hemorrhage is lacking. We hypothesized that in examinable patients without
      neurologic deterioration, RHCT scan does not lead to neurosurgical intervention
      (craniotomy/craniectomy). STUDY DESIGN: This was a 3-year prospective cohort
      analysis of patients aged 18 years and older, without antiplatelet or
      anticoagulation therapy, presenting to our level 1 trauma center with
      intracranial hemorrhage on initial head CT and a follow-up RHCT. Neurosurgical
      intervention was defined by craniotomy/craniectomy. Neurologic deterioration was
      defined as altered mental status, focal neurologic deficits, and/or pupillary
      changes. RESULTS: A total of 1,129 patients were included. Routine RHCT was
      performed in 1,099 patients. The progression rate was 19.7% (216 of 1,099), with
      subsequent neurosurgical intervention in 4 patients. Four patients had an
      abnormal neurologic examination, with a Glasgow Coma Scale (GCS) of <=8 requiring
      intubation. Thirty patients had an RHCT secondary to neurologic deterioration;
      53% (16 of 30) had progression on RHCT, of which 75% (12 of 16) required
      neurosurgical intervention. There was an association between deterioration in
      neurologic examination and need for neurosurgical intervention (odds ratio 3.98;
      95% CI 1.7 to 9.1). The negative predictive value of a deteriorating neurologic
      examination in predicting the need for neurosurgical intervention was 100% in
      patients with GCS > 8. CONCLUSIONS: Routine repeat head CT scan is not warranted
      in patients with normal neurologic examination. Routine repeat head CT scan does
      not supplement the need for neurologic examination for determining management in
      patients with traumatic brain injury.

PMID- 24745623
TI  - Music and surgery: a literary reappraisal.

PMID- 24745624
TI  - Co-infection of Atlantic salmon (Salmo salar), by Moritella viscosa and
      Aliivibrio wodanis, development of disease and host colonization.
AB  - Two species of bacteria are repeatedly isolated from farmed fish with winter
      ulcer disease. Moritella viscosa is the aetiological agent of the disease; the
      significance of Aliivibrio wodanis is uncertain but has not been related to the
      primary pathogenesis. A cell culture infection model showed that A. wodanis
      adhered to, but did not invade the fish cells. Exposure to culture supernatant of
      A. wodanis caused the fish cells to vacoulate, retract, round up and detach from
      the surface, and rearrange the actin filaments of the cytoskeleton. These
      observations suggest that the bacterium secretes toxins into the extracellular
      environment. Any pathologic effect of A. wodanis and the effect of co-culturing
      with M. viscosa was studied in Atlantic salmon (Salmo salar) bath challenged
      with; only M. viscosa or only A. wodanis or both bacteria together. Both M.
      viscosa and A. wodanis were re-isolated from external surfaces and internal
      organs from live and deceased co-infected fish. It is further hypothesized that
      A. wodanis colonization might influence the progression of a M. viscosa
      infection. This is to our knowledge the first study that reproduces field
      observations where both bacteria infect Atlantic salmon. 

PMID- 24745625
TI  - The antigenic drift molecular basis of the H5N1 influenza viruses in a novel
      branch of clade 2.3.4.
AB  - H5N1 subtype influenza A virus has evolved into many HA clades since late 1990 s.
      Six circulating H5N1 influenza viruses clustered to a novel branch in clade 2.3.4
      and could escape vaccine protection, indicating their antigenic drift. Eleven
      amino acids substitutions in three antigenic sites of the hemagglutinin of these
      isolates were found when compared with the hemagglutinin of the primary viruses
      in clade 2.3.4. On the backbone of the novel isolates A/chicken/Northern
      China/k0602/2010, we generated a panel of recombinant viruses with HA mutations
      of restoring the primary vaccine strain Re-5's amino acid and homologous antisera
      to determine the role of these substitutions. The results of cross-HI assay,
      micro-neutralization assay and the antigen map of the mutated recombinant viruses
      showed that three substitutions in antigenic site B, especially D205K, are the
      major contributors to the antigenic drift of the novel branch of clade 2.3.4. Our
      study highlights the importance of surveillance of antigenic drift of H5N1
      viruses for the control and preparedness of pandemic threats.

PMID- 24745626
TI  - DNA vaccination with VP2 gene fragment confers protection against Infectious
      Bursal Disease Virus in chickens.
AB  - Infectious Bursal Disease Virus (IBDV) causes immunosuppression in young chickens
      by destruction of antibody producing B cells in the Bursa of Fabricius and poses
      a potential threat to the poultry industry. We have examined the protective
      efficacy of a subunit DNA vaccine against IBDV infection in chickens in this
      study. An immunodominant VP2 gene fragment (VP252-417) was cloned into CMV
      promoter based DNA vaccine vector pVAX1 and in vitro expression of the DNA
      encoded antigens was confirmed by transfection of CHO cells with vaccine
      constructs followed by RT-PCR and western blot analysis using IBDV-antiserum. Two
      weeks old chickens were immunized intramuscularly with pVAXVP252-417 and the in
      vivo transcription of the plasmid DNA was confirmed by RT-PCR analysis of DNA
      injected muscle tissue at different intervals of post immunization. Tissue
      distribution analysis revealed that the plasmid DNA was extensively distributed
      in muscle, spleen, kidney, liver, and bursa tissues. Chickens immunized with
      pVAXVP252-417 developed high titer (1:12,000) of anti-VP252-417 antibodies.
      Further, chicken splenocytes from pVAXVP252-417 immunized group showed a
      significantly high proliferation to the whole viral and recombinant antigen
      (P<0.01) compared to control groups, which implies that pVAXVP252-417 codes for
      immunogenic fragment which has epitopes capable of eliciting both B and T cell
      responses. This is evident by the fact that, pVAXVP252-417 immunized chicken
      conferred 75% protection against virulent IBDV (vIBDV) challenge compared to the
      control group. Thus, the present study confirms that the immunodominant VP2
      fragment can be used as a potential DNA vaccine against IBDV infection in
      chickens.

PMID- 24745627
TI  - Distribution of Capnocytophaga canimorsus in dogs and cats with genetic
      characterization of isolates.
AB  - Capnocytophaga canimorsus, which is often found in the oral cavities of dogs and
      cats, is sometimes transmitted to humans, causing severe infection. To elucidate
      the risk of C. canimorsus in humans and animals, this study was undertaken to
      characterize this bacterium epidemiologically and genetically. We examined the
      distribution of C. canimorsus in dogs and cats, and analyzed the correlation
      between the presence of bacteria and individual factors statistically. We also
      compared C. canimorsus isolates genetically using 16S rRNA gene sequence analysis
      and pulsed-field gel electrophoresis (PFGE). C. canimorsus was detected in 76 of
      109 dogs (69.7%) and 57 of 104 cats (54.8%). A relation between C. canimorsus
      presence and some individual factors was detected both in dogs and cats, but the
      predictive factors of carrying the bacterium differed between dogs and cats. 16S
      rRNA gene sequences from C. canimorsus isolates in this study were combined with
      previously published sequences to assess their intra-specific phylogeny. Results
      show that C. canimorsus is classifiable into two main groups (I and II) with
      differing gamma-glutamyl aminopeptidase activity. Strains from human patients
      belonged unevenly to group I, possibility suggesting that group I can be
      transmitted to humans and group II is indigenous only to the oral cavities of
      dogs and cats. PFGE genotyping showed high discriminatory power, and the
      dendrogram accorded with genetic segregation between isolates of group I and II.
      Sma I-digest PFGE developed for this study is useful as a molecular typing method
      for additional epidemiological and phylogenetic studies of C. canimorsus.

PMID- 24745628
TI  - Plastic deformation enabled energy dissipation in a bionanowire structured armor.
AB  - It has been challenging to simultaneously achieve high strength and toughness in
      engineered materials because of the trade-off relation between the two distinct
      properties. Nature, however, has elegantly solved this problem. Seashells,
      commonly referred to as nature's armors, exhibit an unusual resilience against
      predatory attacks. In this letter, we report an unexpected phenomenon in a
      bionanowire structured armor-conch shell where the shell's basic building blocks,
      i.e., the third-order lamellae, exhibit an exceptional plasticity with a maximum
      strain of 0.7% upon mechanical loading. We attribute such a plastic deformation
      behavior to the lamella's unique nanoparticle-biopolymer architecture, in which
      the biopolymer mediates the rotation of aragonite nanoparticles in response to
      external attacks. We also found that electron beam irradiation facilitates the
      lamella's plasticity. These findings advance our understanding of seashell's
      energy dissipating strategy and provide new design guidelines for developing high
      performance bioinspired materials and sensors. 

PMID- 24745629
TI  - Reproducibility of maxillofacial landmark identification on three-dimensional
      cone-beam computed tomography images of patients with mandibular prognathism:
      Comparative study of a tentative method and traditional cephalometric analysis.
AB  - OBJECTIVE: To clarify the reproducibility of a tentative method for identifying
      maxillofacial landmarks on three-dimensional (3D) images obtained with cone-beam
      computed tomography (CBCT) for dental use in patients with mandibular
      prognathism. Also, the influence of level of experience of dentists applying the
      method was investigated by dividing them into two groups according to experience.
      MATERIALS AND METHODS: Dentists with less (group A) or more (group B) than 3
      years of experience of cephalometry and 3D image manipulation analyzed CBCT data
      from 10 patients using two different landmark identification methods: method 1
      used conventional cephalometric definitions and method 2 used detailed landmark
      identification definitions developed for each cross-sectional plane. The plotting
      of nine landmarks was performed twice, and 10 coordinate values were obtained for
      each landmark. To assess reproducibility, the 95% confidence ellipse method was
      used. RESULTS: Comparative analysis showed that method 2 was highly reproducible.
      Group B subjects attained smaller ellipsoid volumes than group A subjects,
      regardless of the landmark identification method used. With method 1, except for
      condyle and coronoid process, all landmarks showed a higher level of
      reproducibility in group A subjects than in group B subjects. With method 2,
      however, five landmarks showed no differences between the methods. CONCLUSION:
      The method proposed here may be highly reproducible regardless of the evaluators'
      experience.

PMID- 24745630
TI  - Effect of the length of orthodontic mini-screw implants on their long-term
      stability: a prospective study.
AB  - OBJECTIVE: To analyze the influence of the length of temporary intraoral skeletal
      anchorage devices (TISAD/TAD) on their long-term stability in the mandible in a
      homogenous group of patients. MATERIALS AND METHODS: A group of generally healthy
      patients of the same gender (female) and with a statistically insignificant age
      difference (20-29 years) highly homogenous with respect to known factors
      affecting the success rate of TISAD/TAD was evaluated. One type of TISAD/TAD was
      applied (6- or 8-mm long). Each patient received both 6- and 8-mm-long TISAD/TAD
      in randomly selected mandibular quadrants: left or right. The long-term success
      rate of TISAD/TAD was analyzed. RESULTS: The 8-mm orthodontic mini-screw implants
      were significantly more stable than the 6-mm ones in the analyzed group.
      CONCLUSION: The length of the TISAD/TAD may be one of the factors that can affect
      the long-term success rate in the mandibles of 20- to 29-year-old women.

PMID- 24745632
TI  - Predictors of advanced colorectal neoplasia for colorectal cancer screening.
AB  - BACKGROUND: The Asia-Pacific Colorectal Screening (APCS) score based on age,
      gender, family history, and smoking is useful to predict advanced colorectal
      neoplasia (ACN) in asymptomatic Asian subjects. PURPOSE: To evaluate the factors
      in addition to those of APCS associated with ACN colonoscopic findings. METHODS:
      Data from 5,220 asymptomatic subjects aged between 50 and 70 years who underwent
      screening colonoscopy in a community center between 2008 and 2012 were analyzed.
      One binary logistic regression analysis was conducted in 2013 with the presence
      of ACN or cancer as the outcome, controlling for APCS score, alcohol consumption,
      BMI, hypertension, and other chronic diseases as independent variables. RESULTS:
      The average participant age was 57.7 years (SD=4.9) and 47.5% were men. Advanced
      neoplasms or cancers were identified at colonoscopy in 5.6% of all screening
      participants. From multivariate regression analysis, APCS score>=4 (adjusted OR
      [AOR]=1.74, 95% CI=1.34, 2.25, p<0.001); overweight (BMI=23-24.9, AOR=1.52, 95%
      CI=1.12, 2.07, p=0.007); obesity (BMI>=25, AOR=1.56, 95% CI=1.15, 2.10, p=0.004);
      hypertension (AOR=1.58, 95% CI=1.21, 2.06, p=0.001); and alcohol consumption
      (AOR=1.47, 95% CI=1.05, 2.06, p=0.025) were associated with ACN. The c-statistic
      of APCS score alone was 0.560 (95% CI=0.524, 0.595, p=0.001) and that of APCS
      score plus BMI, hypertension, and alcohol consumption was 0.613 (95% CI=0.578,
      0.648, p<0.001). CONCLUSIONS: Alcohol consumption, hypertension, and BMI are
      independent predictors of ACN, which could be incorporated into the APCS for
      prioritizing Asian asymptomatic subjects for colorectal cancer screening.

PMID- 24745631
TI  - Targeting TGFbeta signaling in subchondral bone and articular cartilage
      homeostasis.
AB  - Osteoarthritis (OA) is the most common degenerative joint disease and no disease
      modifying therapy for OA is currently available. Targeting articular cartilage
      alone may not be sufficient to halt this disease progression. Articular cartilage
      and subchondral bone act as a functional unit. Increasing evidence indicates that
      transforming growth factor beta (TGFbeta) plays a crucial role in maintaining
      homeostasis of both articular cartilage and subchondral bone. Activation of
      extracellular matrix (ECM) latent TGFbeta at the appropriate time and location is
      a prerequisite for its function. Aberrant activation of TGFbeta in the
      subchondral bone in response to an abnormal mechanical loading environment
      induces formation of osteroid islets at the onset of OA. As a result, alteration
      of subchondral bone structure changes the stress distribution on the articular
      cartilage and leads to its degeneration. Thus, inhibition of TGFbeta activity in
      the subchondral bone may provide a new avenue of treatment for OA. In this review
      we will discuss the role of TGFbeta in the homeostasis of articular cartilage and
      subchondral bone as a novel target for OA therapy. 

PMID- 24745633
TI  - Awareness of cancer susceptibility genetic testing: the 2000, 2005, and 2010
      National Health Interview Surveys.
AB  - BACKGROUND: Genetic testing for several cancer susceptibility syndromes is
      clinically available; however, existing data suggest limited population awareness
      of such tests. PURPOSE: To examine awareness regarding cancer genetic testing in
      the U.S. population aged >=25 years in the 2000, 2005, and 2010 National Health
      Interview Surveys. METHODS: The weighted percentages of respondents aware of
      cancer genetic tests, and percent changes from 2000-2005 and 2005-2010, overall
      and by demographic, family history, and healthcare factors were calculated.
      Interactions were used to evaluate the patterns of change in awareness between
      2005 and 2010 among subgroups within each factor. To evaluate associations with
      awareness in 2005 and 2010, percentages were adjusted for covariates using
      multiple logistic regression. The analysis was performed in 2012. RESULTS:
      Awareness decreased from 44.4% to 41.5% (p<0.001) between 2000 and 2005, and
      increased to 47.0% (p<0.001) in 2010. Awareness increased between 2005 and 2010
      in most subgroups, particularly among individuals in the South
      (pinteraction=0.03) or with a usual place of care (pinteraction=0.01). In 2005
      and 2010, awareness was positively associated with personal or family cancer
      history and high perceived cancer risk, and inversely associated with
      racial/ethnic minorities, age 25-39 or >=60 years, male gender, lower education
      and income levels, public or no health insurance, and no provider contact in 12
      months. CONCLUSIONS: Despite improvement from 2005 to 2010, <=50% of the U.S.
      adult population was aware of cancer genetic testing in 2010. Notably,
      disparities persist for racial/ethnic minorities and individuals with limited
      health care access or income.

PMID- 24745634
TI  - Health literacy and injury prevention behaviors among caregivers of infants.
AB  - BACKGROUND: Unintentional injury is a leading cause of infant mortality. PURPOSE:
      To examine the role of caregiver health literacy in infant injury prevention
      behaviors. METHODS: A cross-sectional analysis of data collected in 2010-2012
      from a randomized trial at four pediatric clinics was performed in 2012-2013.
      Caregiver health literacy was assessed with the Short Test of Functional Health
      Literacy in Adults. Caregiver-reported adherence to American Academy of
      Pediatrics-recommended injury prevention behaviors was assessed across seven
      domains: (1) car seat position; (2) car seat use; (3) sleeping safety; (4) fire
      safety; (5) hot water safety; (6) fall prevention; and (7) firearm safety.
      RESULTS: Data were analyzed from 844 English- and Spanish-speaking caregivers of
      2-month-old children. Many caregivers were non-adherent with injury prevention
      guidelines, regardless of health literacy. Notably, 42.6% inappropriately placed
      their children in the prone position to sleep, and 88.6% did not have their hot
      water heater set <120 degrees F. Eleven percent of caregivers were categorized as
      having low health literacy. Low caregiver health literacy, compared to adequate
      health literacy, was significantly associated with increased odds of caregiver
      non-adherence with recommended behaviors for car seat position (AOR=3.4, 95%
      CI=1.6, 7.1) and fire safety (AOR=2.0, 95% CI=1.02, 4.1) recommendations.
      Caregivers with low health literacy were less likely to be non-adherent to fall
      prevention recommendations (AOR=0.5, 95% CI=0.2, 0.9). CONCLUSIONS: Non-adherence
      to injury prevention guidelines was common. Low caregiver health literacy was
      significantly associated with some injury prevention behaviors. Future
      interventions should consider the role of health literacy in promoting injury
      prevention.

PMID- 24745636
TI  - Obesity-related health status changes and weight-loss treatment utilization.
AB  - BACKGROUND: Behavioral weight-loss treatment can improve health, yet it is
      underutilized. Factors leading to initiation of weight-loss treatment are not
      well characterized. In particular, it is unknown whether changes in obesity
      related health status contribute to weight-loss treatment initiation. PURPOSE: To
      determine if recent weight change or diagnosis of an obesity-related comorbidity
      was associated with utilization of a behavioral weight-loss program in an
      integrated healthcare setting. METHODS: In a retrospective cohort study of 45,272
      Veterans Affairs (VA) patients with BMI >30, logistic regression was used to
      examine whether recent weight change or obesity-related comorbidities newly
      diagnosed in the past 6 months were associated with initiation of a VA behavioral
      weight management program (called MOVE!) in 2010 or sustained MOVE! use (eight or
      more sessions). Weight change in prior year was categorized as >3% weight loss;
      weight stable (<3% change); or weight gain of 3%-4.9%, 5%-9.9%, or >=10%. Data
      were analyzed in 2013. RESULTS: Patients were 91% male, 68% white, and had a mean
      age of 58 years. Patients were more likely to initiate treatment if they had >=3%
      weight gain (3%-4.9%: OR=1.64, 95% CI=1.52, 1.77; 5%-9.9%: OR=1.99, 95% CI=1.84,
      2.16; >=10%: OR=2.68, 95% CI=2.32, 3.10) or were newly diagnosed with any obesity
      related comorbidity (ORs: 2.14-3.59). Weight change and new comorbidity diagnoses
      were not associated, however, with sustained MOVE! use. CONCLUSIONS: Adverse
      obesity-related health events were associated with initiation of behavioral
      weight-loss treatment offered in an integrated healthcare setting.

PMID- 24745635
TI  - Automating assessment of lifestyle counseling in electronic health records.
AB  - BACKGROUND: Numerous population-based surveys indicate that overweight and obese
      patients can benefit from lifestyle counseling during routine clinical care.
      PURPOSE: To determine if natural language processing (NLP) could be applied to
      information in the electronic health record (EHR) to automatically assess
      delivery of weight management-related counseling in clinical healthcare
      encounters. METHODS: The MediClass system with NLP capabilities was used to
      identify weight-management counseling in EHRs. Knowledge for the NLP application
      was derived from the 5As framework for behavior counseling: Ask (evaluate weight
      and related disease), Advise at-risk patients to lose weight, Assess patients'
      readiness to change behavior, Assist through discussion of weight-loss methods
      and programs, and Arrange follow-up efforts including referral. Using samples of
      EHR data between January 1, 2007, and March 31, 2011, from two health systems,
      the accuracy of the MediClass processor for identifying these counseling elements
      was evaluated in postpartum visits of 600 women with gestational diabetes
      mellitus (GDM) compared to manual chart review as the gold standard. Data were
      analyzed in 2013. RESULTS: Mean sensitivity and specificity for each of the 5As
      compared to the gold standard was at or above 85%, with the exception of
      sensitivity for Assist, which was 40% and 60% for each of the two health systems.
      The automated method identified many valid Assist cases not identified in the
      gold standard. CONCLUSIONS: The MediClass processor has performance capability
      sufficiently similar to human abstractors to permit automated assessment of
      counseling for weight loss in postpartum encounter records.

PMID- 24745637
TI  - Long-lasting permethrin impregnated uniforms: A randomized-controlled trial for
      tick bite prevention.
AB  - BACKGROUND: Because of frequent exposure to tick habitats, outdoor workers are at
      high risk for tick-borne diseases. Adherence to National Institute for
      Occupational Safety and Health-recommended tick bite prevention methods is poor.
      A factory-based method for permethrin impregnation of clothing that provides long
      lasting insecticidal and repellent activity is commercially available, and
      studies are needed to assess the long-term effectiveness of this clothing under
      field conditions. PURPOSE: To evaluate the protective effectiveness of long
      lasting permethrin impregnated uniforms among a cohort of North Carolina outdoor
      workers. DESIGN, SETTING, AND PARTICIPANTS: A double-blind RCT was conducted
      between March 2011 and September 2012. Subjects included outdoor workers from
      North Carolina State Divisions of Forestry, Parks and Recreation, and Wildlife
      who worked in eastern or central North Carolina. A total of 159 volunteer
      subjects were randomized, and 127 and 101 subjects completed the first and second
      years of follow-up, respectively. INTERVENTION: Uniforms of participants in the
      treatment group were factory-impregnated with long-lasting permethrin whereas
      control group uniforms received a sham treatment. Participants continued to
      engage in their usual tick bite prevention activities. MAIN OUTCOME MEASURES:
      Incidence of work-related tick bites reported on weekly tick bite logs. RESULTS:
      Study subjects reported 1,045 work-related tick bites over 5,251 person-weeks of
      follow-up. The mean number of reported tick bites in the year prior to enrollment
      was similar for both the treatment and control groups, but markedly different
      during the study period. In our analysis conducted in 2013, the effectiveness of
      long-lasting permethrin impregnated uniforms for the prevention of work-related
      tick bites was 0.82 (95% CI=0.66, 0.91) and 0.34 (95% CI=-0.67, 0.74) for the
      first and second years of follow-up. CONCLUSIONS: These results indicate that
      long-lasting permethrin impregnated uniforms are highly effective for at least 1
      year in deterring tick bites in the context of typical tick bite prevention
      measures employed by outdoor workers.

PMID- 24745638
TI  - A comparison of carbon monoxide exposures after snowstorms and power outages.
AB  - BACKGROUND: Unintentional carbon monoxide poisoning occurs frequently after
      natural disasters. Although the epidemiology of carbon monoxide exposures that
      occur after power loss storms has been reported, few publications detail the
      characteristics of carbon monoxide exposures after massive snowstorms. PURPOSE:
      To compare the differences in patient characteristics of carbon monoxide
      exposures after a snowstorm and power loss storm. METHODS: In 2013, a
      retrospective review was conducted of patient characteristics and exposure data
      from all carbon monoxide cases reported to the Connecticut Poison Control Center
      in the days following both a major snowstorm in 2013 and a winter storm that
      caused extensive power outages in 2011. RESULTS: Portable generators were the
      most common source of carbon monoxide exposure after a storm that resulted in
      power losses; car exhaust was the most frequent source of exposure after an
      extensive snowstorm. Most exposures occurred within the first day after the
      snowstorm, and on the second and third days after the power outage storm. There
      were no significant differences between the two storms in terms of patient age,
      gender, or median carboxyhemoglobin concentration. CONCLUSIONS: Future public
      health and medical education regarding the dangers of carbon monoxide in the
      aftermath of storms should include attention to the differences in the typical
      exposure sources and timing.

PMID- 24745639
TI  - Evaluation of a mass media campaign promoting using help to quit smoking.
AB  - BACKGROUND: Although there is evidence that promoting individual cessation aids
      increases their utilization, mass media campaigns highlighting the benefit of
      using help to quit have not been evaluated. PURPOSE: The effects of a
      Philadelphia adult smoking-cessation media campaign targeting using help in ad
      taglines were analyzed from March to November 2012. This study distinctively
      analyzed the campaign's impact at both the population level (effects on the
      average person) and the individual level (effects among those who reported
      exposure). METHODS: The 16-month mass media campaign aired in Philadelphia PA
      from December 2010 to March 2012. A representative sample of adult Philadelphia
      smokers was interviewed by telephone at baseline (n=491) and new samples were
      interviewed monthly throughout the campaign (n=2,786). In addition, a subsample
      of these respondents was reinterviewed 3 months later (n=877). RESULTS: On
      average, participants reported seeing campaign ads four times per week. Among
      individual respondents, each additional campaign exposure per week increased the
      likelihood of later reporting using help (OR=1.08, p<0.01), adjusting for
      baseline use of help and other potential confounders. This corresponded to a 5%
      increase in the use of help for those with average exposure relative to those
      with no exposure. Cross-sectional associations between individual campaign
      exposure and intentions to use help were consistent with these lagged findings.
      However, there was no evidence of population-level campaign effects on use of
      help. CONCLUSIONS: Although the campaign was effective at the individual level,
      its effects were too small to have a population-detectable impact.

PMID- 24745641
TI  - Active transportation and adolescents' health: the Canadian Health Measures
      Survey.
AB  - BACKGROUND: Active transportation (AT; e.g., walking and cycling) is increasingly
      promoted to increase youth physical activity (PA). Most previous research focused
      solely on school trips, and associations among AT and cardiovascular risk factors
      have seldom been examined in adolescents. PURPOSE: To address these important
      research gaps using data from the nationally representative 2007-2009 Canadian
      Health Measures Survey. METHODS: A total of 1,016 adolescents aged 12-19 years
      reported their weekly time spent utilitarian walking and cycling, and wore an
      Actical accelerometer for 7 days. They underwent a series of physical tests
      (measures of fitness, body composition, blood pressure, and blood sampling)
      following standardized protocols. In 2013, differences in PA and health-related
      outcomes across levels of walking and cycling were assessed with ANCOVA analyses
      adjusted for age, gender, parental education, and usual daily PA. RESULTS:
      Greater walking and cycling time was associated with higher moderate-to-vigorous
      PA (MVPA). Compared to adolescents reporting walking 1-5 hours/week, those
      reporting <1 hour/week had lower waist circumference and total cholesterol/high
      density lipoprotein (HDL) ratio and higher glycohemoglobin; those reporting >5
      hours/week had better grip strength, lower total cholesterol, and total
      cholesterol/HDL ratio. Compared to adolescents reporting no cycling, those
      reporting >=1 hour/week accumulated more light PA, had greater aerobic fitness,
      and lower BMI, waist circumference, and total cholesterol/HDL ratio; those who
      reported cycling <1 hour/week had lower total cholesterol. CONCLUSIONS:
      Utilitarian walking and cycling were associated with higher daily MVPA in youth.
      Cycling was associated with a more consistent pattern of health benefits than
      walking.

PMID- 24745640
TI  - Smoking among U.S. Hispanic/Latino adults: the Hispanic community health
      study/study of Latinos.
AB  - BACKGROUND: Prior national surveys capture smoking behaviors of the aggregated
      U.S. Hispanic/Latino population, possibly obscuring subgroup variation. PURPOSE:
      To describe cigarette use among Hispanic/Latino adults across subgroups of age,
      gender, national background, SES, birthplace, and degree of acculturation to the
      dominant U.S. culture. METHODS: A cross-sectional survey of 16,322 participants
      in the Hispanic Community Health Study/Study of Latinos aged 18-74 years,
      recruited in Bronx NY, Chicago IL, Miami FL, and San Diego CA, was conducted
      during 2008-2011. RESULTS: Prevalence of current smoking was highest among Puerto
      Ricans (men, 35.0%; women, 32.6%) and Cubans (men, 31.3%; women, 21.9%), with
      particularly high smoking intensity noted among Cubans as measured by pack-years
      and cigarettes/day. Dominicans had the lowest smoking prevalence (men, 11.0%;
      women, 11.7%). Individuals of other national backgrounds had a smoking prevalence
      that was intermediate between these groups, and typically higher among men than
      women. Non-daily smoking was common, particularly although not exclusively among
      young men of Mexican background. Persons of low SES were more likely to smoke,
      less likely to have quit smoking, and less frequently used over-the-counter quit
      aids compared to those with higher income and education levels. Smoking was more
      common among individuals who were born in the U.S. and had a higher level of
      acculturation to the dominant U.S. culture, particularly among women.
      CONCLUSIONS: Smoking behaviors vary widely across Hispanic/Latino groups in the
      U.S., with a high prevalence of smoking among population subgroups with specific,
      readily identifiable characteristics.

PMID- 24745642
TI  - Consumer sentiment on actions reducing sodium in processed and restaurant foods,
      ConsumerStyles 2010.
AB  - BACKGROUND: Current recommendations target sodium reduction in the food supply
      and intake; however, information is limited on consumer readiness for these
      actions. PURPOSE: Prevalence and determinants of consumer agreement for
      government restriction of manufacturers and restaurants putting excess salt in
      food and support for policies limiting sodium content of quick service restaurant
      (QSR) foods were examined. METHODS: Data were analyzed from 9,579 adults aged
      >=18 years who responded to consumer readiness for sodium reduction questions in
      the 2010 ConsumerStyles survey. Responses were collapsed into three categories.
      Consumer agreement was determined and logistic regression was used to estimate
      ORs. Analyses were conducted in 2012. RESULTS: The majority of consumers agree
      that it is a good idea for government to restrict food manufacturers (55.9%) from
      putting excess salt in foods. About half agreed that it is a good idea for
      government to restrict restaurants from putting excess salt in foods and 81.5%
      supported sodium reduction policies in QSRs. Odds of agreement/support were
      higher for non-Hispanic blacks compared with non-Hispanic whites, and those with
      incomes <$40,000 compared with >=$60,000. Those reporting "neutral" or "yes" to
      wanting to eat a diet low in sodium were more likely to agree/support government
      action compared to those answering "no." CONCLUSIONS: Nearly half of consumers
      agree with government actions to reduce sodium in manufactured and restaurant
      foods, with even greater support for QSRs. These findings could inform industry
      and public health partners about consumer preferences to lower the sodium content
      of the food supply.

PMID- 24745643
TI  - Feasibility of retrofitting a university library with active workstations to
      reduce sedentary behavior.
AB  - BACKGROUND: Libraries are an inherently sedentary environment, but are an
      understudied setting for sedentary behavior interventions. PURPOSE: To
      investigate the feasibility of incorporating portable pedal machines in a
      university library to reduce sedentary behaviors. METHODS: The 11-week
      intervention targeted students at a university library. Thirteen portable pedal
      machines were placed in the library. Four forms of prompts (e-mail, library
      website, advertisement monitors, and poster) encouraging pedal machine use were
      employed during the first 4 weeks. Pedal machine use was measured via automatic
      timers on each machine and momentary time sampling. Daily library visits were
      measured using a gate counter. Individualized data were measured by survey. Data
      were collected in fall 2012 and analyzed in 2013. RESULTS: Mean (SD) cumulative
      pedal time per day was 95.5 (66.1) minutes. One or more pedal machines were
      observed being used 15% of the time (N=589). Pedal machines were used at least
      once by 7% of students (n=527). Controlled for gate count, no linear change of
      pedal machine use across days was found (b=-0.1 minutes, p=0.75) and the presence
      of the prompts did not change daily pedal time (p=0.63). Seven of eight items
      that assessed attitudes toward the intervention supported intervention
      feasibility (p<0.05). CONCLUSIONS: The unique non-individualized approach of
      retrofitting a library with pedal machines to reduce sedentary behavior seems
      feasible, but improvement of its effectiveness is needed. This study could inform
      future studies aimed at reshaping traditionally sedentary settings to improve
      public health.

PMID- 24745644
TI  - Publicized sobriety checkpoint programs: a community guide systematic review.
AB  - CONTEXT: Publicized sobriety checkpoint programs deter alcohol-impaired driving
      by stopping drivers systematically to assess their alcohol impairment. Sobriety
      checkpoints were recommended in 2001 by the Community Preventive Services Task
      Force for reducing alcohol-impaired driving, based on strong evidence of
      effectiveness. Since the 2001 review, attention to alcohol-impaired driving as a
      U.S. public health problem has decreased. This systematic review was conducted to
      determine if available evidence supports the effectiveness of publicized sobriety
      checkpoint programs in reducing alcohol-impaired driving, given the current
      context. The economic costs and benefits of the intervention were also assessed.
      EVIDENCE ACQUISITION: This review focused on studies that evaluated the effects
      of publicized sobriety checkpoint programs on alcohol-involved crash fatalities.
      Using Community Guide methods, a systematic search was conducted for studies
      published between July 2000 and March 2012 that assessed the effectiveness of
      publicized sobriety checkpoint programs. EVIDENCE SYNTHESIS: Fourteen evaluations
      of selective breath testing and one of random breath testing checkpoints met the
      inclusion criteria for the systematic review, conducted in 2012. Ten evaluations
      assessed the effects of publicized sobriety checkpoint programs on alcohol
      involved crash fatalities, finding a median reduction of 8.9% in this crash type
      (interquartile interval=-16.5%, -3.5%). Five economic evaluations showed benefit
      cost ratios ranging from 2:1 to 57:1. CONCLUSIONS: The number of studies,
      magnitude of effect, and consistency of findings indicate strong evidence of the
      effectiveness of publicized sobriety checkpoint programs in reducing alcohol
      involved crash fatalities. Economic evidence shows that these programs also have
      the potential for substantial cost savings.

PMID- 24745645
TI  - Publicized sobriety checkpoint programs to reduce alcohol-impaired driving:
      recommendation of the Community Preventive Services Task Force.

PMID- 24745646
TI  - Toward a county-level map of tuberculosis rates in the U.S.

PMID- 24745647
TI  - Polypyrrolic bipyridine bis(phenantrolinequinone) Ru(II) complex/carbon nanotube
      composites for NAD-dependent enzyme immobilization and wiring.
AB  - We report the synthesis and electrochemical characterization of a novel
      electropolymerizable Ru(II) complex containing two phenanthrolinequinone ligands,
      Ru(II)(PhQ)2(bpy-pyrrole)(PF6)2. This complex was electropolymerized on glassy
      carbon (GC) and multiwalled carbon nanotube (MWCNT) electrodes. Higher apparent
      surface concentrations (80 nmol cm(-2)) were obtained on MWCNTs than on GC
      electrodes and correspond to ~1000 equivalent compact monolayers of Ru complex.
      Moreover, the nanostructured metallopolymer exhibits efficient electrocatalytic
      properties toward oxidation of NADH. This metallopolymer can be electrogenerated
      in water from the adsorbed Ru(II) monomer. This property was applied to the
      immobilization of enzymes by coadsorption of Ru complex and enzyme and then
      electropolymerization of coatings. This two-step procedure leads to the
      entrapment of 70%-90% of the deposited amount of enzyme in poly-Ru(II)(PhQ)2(bpy
      pyrrole) films. Glucose dehydrogenase (GDH) was thus efficiently immobilized in
      the electrogenerated polymer matrix. In presence of NAD(+) (10 mM), the resulting
      enzyme electrode exhibits high current densities for glucose oxidation of 1.04 mA
      cm(-2) at low overpotentials (-0.1 V) with a detection limit of 1 MUM of glucose.

PMID- 24745648
TI  - Parenteral glutamine supplementation in critical illness: a systematic review.
AB  - INTRODUCTION: The potential benefit of parenteral glutamine (GLN) supplementation
      has been one of the most commonly studied nutritional interventions in the
      critical care setting. The aim of this systematic review was to incorporate
      recent trials of traditional parenteral GLN supplementation in critical illness
      with previously existing data. METHODS: All randomized controlled trials of
      parenterally administered GLN in critically ill patients conducted from 1997 to
      2013 were identified. Studies of enteral GLN only or combined enteral/parenteral
      GLN were excluded. Methodological quality of studies was scored and data was
      abstracted by independent reviewers. RESULTS: A total of 26 studies involving
      2,484 patients examining only parenteral GLN supplementation of nutrition support
      were identified in ICU patients. Parenteral GLN supplementation was associated
      with a trend towards a reduction of overall mortality (relative risk (RR) 0.88,
      95% confidence interval (CI) 0.75, 1.03, P = 0.10) and a significant reduction in
      hospital mortality (RR 0.68, 95% CI 0.51, 0.90, P = 0.008). In addition,
      parenteral GLN was associated with a strong trend towards a reduction in
      infectious complications (RR 0.86, 95% CI 0.73, 1.02, P = 0.09) and ICU length of
      stay (LOS) (WMD -1.91, (95% CI -4.10, 0.28, P = 0.09) and significant reduction
      in hospital LOS (WMD -2.56, 95% CI -4.71, -0.42, P = 0.02). In the subset of
      studies examining patients receiving parenteral nutrition (PN), parenteral GLN
      supplementation was associated with a trend towards reduced overall mortality (RR
      0.84, 95% CI 0.71, 1.01, P = 0.07). CONCLUSIONS: Parenteral GLN supplementation
      given in conjunction with nutrition support continues to be associated with a
      significant reduction in hospital mortality and hospital LOS. Parenteral GLN
      supplementation as a component of nutrition support should continue to be
      considered to improve outcomes in critically ill patients.

PMID- 24745649
TI  - Morbidity and mortality among very-low-birth-weight infants born to mothers with
      clinical chorioamnionitis.
AB  - BACKGROUND: Controversy exists about the relationship between maternal
      inflammation and the development of different morbidities and mortality in the
      newborn. We aimed to establish the incidence of clinical chorioamnionitis in our
      Neonatal Intensive Care Unit and its relation to morbidity and mortality among
      very-low-birth-weight infants. METHODS: This was an observational study of a
      cohort of very-low-birth-weight neonates admitted to our Neonatal Intensive Care
      Unit, between January 2008 and December 2012. Demographic characteristics and
      outcomes were analyzed and a comparison between exposed and non-exposed infants
      was carried out. RESULTS: During the study period, 451 very-low-birth-weight
      infants were admitted to our Neonatal Intensive Care Unit, and 31 (6.87%) were
      exposed to maternal clinical chorioamnionitis. The incidence was higher at lower
      gestational ages: 13.2% (23-26 weeks), 8.1% (27-30 weeks), and 2.6% (31-34 weeks)
      (p = 0.022). After correcting by gestational age and birth weight, early-onset
      neonatal sepsis (adjusted relative risk = 6.13; 95% confidence interval = 1.67
      22.58; p = 0.006) and periventricular leukomalacia (adjusted relative risk =
      24.62; 95% confidence interval = 1.87-324.28; p = 0.015) were significantly
      associated with maternal clinical chorioamnionitis. There were no differences in
      mortality or in survival without major morbidity. CONCLUSION: Clinical
      chorioamnionitis confers an increased risk of early-onset neonatal sepsis and
      periventricular leukomalacia to exposed very-low-birth-weight infants.

PMID- 24745650
TI  - Correlation between gastroesophageal reflux disease questionnaire and erosive
      esophagitis in school-aged children receiving endoscopy.
AB  - BACKGROUND: The gastroesophageal reflux disease (GERD) questionnaire (GerdQ) is a
      validated questionnaire that was developed recently to help identify GERD
      patients. The sensitivity and specificity of GerdQ for the diagnosis of GERD in
      adult patients were 65% and 71%, respectively. Because the application of GerdQ
      in pediatric population is largely unknown, the aim of this study is to establish
      the endoscopic correlation between Chinese GerdQ and grades of erosive
      esophagitis (EE) in Taiwanese children. METHODS: Seventy-four children (aged 9-18
      years) were evaluated by our version of the Chinese GerdQ prior to receiving
      esophagogastroduodenoscopy for warning upper gastrointestinal symptoms. Grades of
      EE were assessed blindly, according to the Los Angeles classification. The
      sensitivity and specificity of GerdQ for detecting endoscopic EE were analyzed.
      RESULTS: In 74 patients, the male to female ratio was 1:1.1 and the mean age was
      14.2 +/- 2.3 years (age range: 9.2-17.9 years). Thirty-nine percent of the
      enrolled patients had EE. The sensitivity and specificity of GerdQ (with a cutoff
      score of >=7) to identify EE patients were 65.5% and 80%, respectively. The odds
      ratio of GerdQ for a cutoff score of 7 to identify EE was 7.6 (95% confidence
      interval = 2.6-21.9, p < 0.001). CONCLUSION: For the identification of EE in
      children, the Chinese GerdQ had similar sensitivity and specificity to that used
      for adults. This questionnaire may be applied as a noninvasive screening tool.

PMID- 24745651
TI  - Policy encouraging earlier hip fracture surgery can decrease the long-term
      mortality of elderly patients.
AB  - BACKGROUND: In April 2004 the Israeli Ministry of Health decided to condition DRG
      payment for hip surgery by time between hospitalisation and operation, giving a
      fine for every day's delay beyond 48h. An evaluation study performed 2 years
      after the reform has shown the positive influence of the reform on patient's
      survival in the hospital. This study evaluates the impact of the reform on the
      longer-term mortality of patients. METHODS: A retrospective study based on data
      from nine hospitals of the national trauma registry available for the years 2001
      2007, with surveillance on 2-year survival through data of Ministry of the
      Interior. The study population includes patients aged 65 and above with an
      isolated hip fracture following trauma. Mortality curves and Cox regression were
      utilised to compare the influence of different parameters on long-term mortality.
      RESULTS: Earlier surgery had a significant positive impact on survival through
      the whole length of the study period. In the period after the introduction of the
      new reimbursement system for hip fracture surgeries, a significant decrease in
      the longer-term mortality was observed up to 6 months of follow-up, even when
      adjusted by patients' age, gender and the receiving hospital. After 6 months
      there was no further decrease in relative risk, though the survival advantage
      remained with patients hospitalised after the reform. CONCLUSIONS: The reform
      appears successful in decreasing the longer-term patient mortality after hip
      fracture through influencing surgical practice.

PMID- 24745652
TI  - Mortality in cancer patients after a fall-related injury: The impact of cancer
      spread and type.
AB  - BACKGROUND: Cancer patients are at an increased risk of dying following an
      injury, of which among the elderly is predominately caused by falling. In
      addition, patients with certain types of cancer are more prone to bone injury.
      However, studies are needed that examine the role of cancer site and metastasis
      on the relationship between cancer and death following traumatic injury. METHODS:
      A total of 4201 cancer patients from 2000 to 2009 in the Illinois Hospital
      Discharge and Illinois Trauma Registry, and 4201 patients without cancer met
      eligibility criteria (e.g., fell and were injured; 50-96 years old). A
      multivariable logistic regression analysis was conducted to assess the
      relationship between cancer and death following traumatic injury, including
      models stratified by cancer site and metastasis. RESULTS: The demographic
      characteristics, prevalence of comorbid conditions, and injury severity and type
      did not differ substantially between patients with and without diagnoses for
      cancer. In the main adjusted model, patients with cancer were more likely to die
      during the course of hospitalization after a fall than those without cancer
      (OR=2.58; CI 95%: 1.91-3.49). Patients with metastatic malignancies had a higher
      risk of in-hospital death than patients without metastasis (adjusted OR=3.59 and
      OR=2.18, respectively). Patients with diagnoses for all specific cancer sites,
      except prostate and breast, were also significantly more likely to die.
      DISCUSSION: Cancer patients with and without spread over the age of 50 years are
      more likely to die in-hospital after a fall than elderly patients without cancer.
      However, this relationship may exist only for patients with specific cancer
      types.

PMID- 24745653
TI  - IGF-I receptor 275124A>C (rs1464430) polymorphism and athletic performance.
AB  - OBJECTIVES: To examine the prevalence of the Insulin-Like Growth Factor-I
      receptor (IGF-IR) 275124A>C polymorphism, known to be associated with exercise
      related cardiac hypertrophy, among elite endurance and power athletes. DESIGN:
      One hundred and fifty-nine athletes (118 men and 41 women, age: 35.9+/-12.2 yrs)
      participated in the study. METHODS: We hypothesized that presence of the A allele
      will be significantly more common among endurance athletes (n=77) compared to
      power athletes (n=82) and non-physically active controls (n=68). Athletes within
      each group were further divided according to their individual best performance
      into elite athletes (those who had represented the country in international track
      and-field or triathlon competitions or in the Olympic Games) and national-level
      athletes. RESULTS: The prevalence of the AA genotype was significantly higher
      (p<0.05) in the endurance athletes group (49%) compared to the power athletes
      group (33%), but did not differ from the control group (46%). There was no
      significant difference in the prevalence of the AA genotype between elite and
      national level endurance athletes (44% versus 52%, respectively). In contrast,
      among power athletes, the prevalence of the AA genotype was significantly lower
      in the elite compared to national level athletes (17% versus 42%, respectively;
      p<0.05). CONCLUSIONS: The results of the present study may suggest that the IGF
      IR AA polymorphism is beneficial for endurance-type sports, but is not associated
      with elite endurance performance. In contrast, the presence of the AA genotype
      may be a disadvantage in power sports. All together the results of the present
      study suggest that IGF-IR polymorphism may differentiate between the two edges of
      the endurance-power athletic performance spectrum.

PMID- 24745654
TI  - Variability in the antioxidant activity of dietary supplements from pomegranate,
      milk thistle, green tea, grape seed, goji, and acai: effects of in vitro
      digestion.
AB  - The antioxidant activity (AA) of fruits and vegetables has been thoroughly
      investigated but less is known about the AA of dietary supplements (DS). We
      therefore assessed the AA of three to five DS each from pomegranate, milk
      thistle, green tea, grapes, goji, and acai using four widely used standard
      methods. The secondary objective was to determine the effects of in vitro
      digestion on their AA. The AA of the DS prior to digestion ranked as follows:
      pomegranate > resveratrol > green tea > grape seed > milk thistle and very low in
      goji and acai with significant group variability in AA. The AA after in vitro
      simulated digestion of the mouth, stomach, and small intestine compared to
      undigested supplement was decreased for green tea and grape seed but increased
      for pomegranate, resveratrol, milk thistle, goji, and acai to various extents.
      Although polyphenols provide the major antioxidant potency of the tested
      supplements, our observations indicate that digestion may alter antioxidant
      properties depending in part on the variations in polyphenol content. 

PMID- 24745655
TI  - Catalytic conversion of nonfood woody biomass solids to organic liquids.
AB  - This Account outlines recent efforts in our laboratories addressing a fundamental
      challenge of sustainability chemistry, the effective utilization of biomass for
      production of chemicals and fuels. Efficient methods for converting renewable
      biomass solids to chemicals and liquid fuels would reduce society's dependence on
      nonrenewable petroleum resources while easing the atmospheric carbon dioxide
      burden. The major nonfood component of biomass is lignocellulose, a matrix of the
      biopolymers cellulose, hemicellulose, and lignin. New approaches are needed to
      effect facile conversion of lignocellulose solids to liquid fuels and to other
      chemical precursors without the formation of intractable side products and with
      sufficient specificity to give economically sustainable product streams. We have
      devised a novel catalytic system whereby the renewable feedstocks cellulose,
      organosolv lignin, and even lignocellulose composites such as sawdust are
      transformed into organic liquids. The reaction medium is supercritical methanol
      (sc-MeOH), while the catalyst is a copper-doped porous metal oxide (PMO) prepared
      from inexpensive, Earth-abundant starting materials. This transformation occurs
      in a single stage reactor operating at 300-320  degrees C and 160-220 bar. The
      reducing equivalents for these transformations are derived by the reforming of
      MeOH (to H2 and CO), which thereby serves as a "liquid syngas" in the present
      case. Water generated by deoxygenation processes is quickly removed by the water
      gas shift reaction. The Cu-doped PMO serves multiple purposes, catalyzing
      substrate hydrogenolysis and hydrogenation as well as the methanol reforming and
      shift reactions. This one-pot "UCSB process" is quantitative, giving little or no
      biochar residual. Provided is an overview of these catalysis studies beginning
      with reactions of the model compound dihydrobenzofuran that help define the key
      processes occurring. The initial step is phenyl-ether bond hydrogenolysis, and
      this is followed by aromatic ring hydrogenation. The complete catalytic
      disassembly of the more complex organosolv lignin to monomeric units, largely
      propyl-cyclohexanol derivatives is then described. Operational indices based on
      (1)H NMR analysis are also presented that facilitate holistic evaluation of these
      product streams that within several hours consist largely of propyl-cyclohexanol
      derivatives. Lastly, we describe the application of this methodology with several
      types of wood (pine sawdust, etc.) and with cellulose fibers. The product
      distribution, albeit still complex, displays unprecedented selectivity toward the
      production of aliphatic alcohols and methylated derivatives thereof. These
      observations clearly indicate that the Cu-doped solid metal oxide catalyst
      combined with sc-MeOH is capable of breaking down the complex biomass derived
      substrates to markedly deoxygenated monomeric units with increased hydrogen
      content. Possible implementations of this promising system on a larger scale are
      discussed.

PMID- 24745656
TI  - Cannabis withdrawal in patients with and without opioid dependence.
AB  - BACKGROUND: Cannabis use is common among opioid-dependent individuals, but little
      is known about cannabis withdrawal in this population. METHODS: Thirty inpatients
      (57% men) completed the Marijuana Quit Questionnaire (MJQQ) after completing
      acute heroin detoxification treatment in Saint Petersburg, Russia. The MJQQ
      collected data on motivations for quitting, withdrawal symptoms, and coping
      strategies used to help maintain abstinence during their most "serious" (self
      defined) quit attempt made without formal treatment outside a controlled
      environment. RESULTS: At the start of their quit attempt, 70% of participants
      smoked cannabis at least weekly (40% daily), averaging [SD] 2.73 [1.95] joints
      daily; 60% were heroin dependent. Subjects with heroin dependence were
      significantly older at the start of their quit attempt (22.9 [3.6] vs. 19.1 [2.9]
      years), were significantly less likely to report withdrawal
      irritability/anger/aggression (22% vs. 58%), restlessness (0% vs. 25%), or
      physical symptoms (6% vs. 33%), or to meet diagnostic criteria for DSM-5
      (Diagnostic and Statistical Manual of Mental Disorders, 5th edition) cannabis
      withdrawal syndrome (6% vs. 33%), and had shorter duration of abstinence (29.6
      [28.7] vs 73.7 [44.1] months) than those without heroin dependence. CONCLUSION:
      Cannabis users with opioid dependence are less likely to experience cannabis
      withdrawal, suggesting that opiate use may prevent or mask the experience of
      cannabis withdrawal. RESULTS should be considered preliminary due to small
      convenience sample and retrospective data.

PMID- 24745657
TI  - Timelier notification and action with mobile phones-towards malaria elimination
      in South Africa.
AB  - BACKGROUND: Surveillance with timely follow-up of diagnosed cases is a key
      component of the malaria elimination strategy in South Africa. The strategy
      requires each malaria case to be reported within 24 hours, and a case should be
      followed up within 48 hours. However, reporting delays are common in rural parts
      of the country. METHODS: A technical framework was implemented and for eight
      months a nurse was hired to use a smartphone to report malaria cases to the
      provincial malaria control programme, from selected primary health care clinics
      in a rural, malaria-endemic area in South Africa. In addition, a short text
      message (SMS) notification was sent to the local malaria case investigator for
      each positive case. The objective was to assess whether reporting over the
      smartphone led to timelier notification and follow-up of the cases. An evaluation
      on the simplicity, flexibility, stability, acceptability, and usability of the
      framework was conducted. RESULTS: Using mobile reporting, 18 of 23 cases had
      basic information entered into the provincial malaria information system within
      24 hours. For the study period, the complete case information was entered two to
      three weeks earlier with the mobile reporting than from other clinics. A major
      improvement was seen in the number of positive cases being followed up within 48
      hours. In 2011/2012, only one case out of 22 reported from the same study clinics
      was followed up within this timeframe. During the study period in 2012/2013, 15
      cases out of 23 were followed up within two days. For the other clinics in the
      area, only a small improvement was seen between the two periods, in the
      proportion of cases that was followed up within 48 hours. CONCLUSIONS: SMS
      notification for each diagnosed malaria case improved the timeliness of data
      transmission, was acceptable to users and was technically feasible in this rural
      area. For the malaria case investigations, time to follow-up improved compared to
      other clinics. Although malaria case numbers in the study were small, the results
      of the qualitative and quantitative evaluations are convincing and consideration
      should be given to larger-scale use within the national malaria control
      programme.

PMID- 24745658
TI  - Severe Plasmodium vivax malaria complicated with acute respiratory distress
      syndrome: a case associated with focal autochthonous transmission in Greece.
AB  - In 2011, autochthonous Plasmodium vivax malaria emerged in a focal geographical
      area in Greece after importation by immigrants from the Indian subcontinent. We
      report the case of complicated P. vivax malaria in a previously healthy 42-year
      old Greek female. The patient presented acute respiratory distress syndrome
      (ARDS), worsening jaundice, and thrombocytopenia after the administration of
      antimalarial treatment and despite a decreasing burden of parasitemia. She
      recovered fully after admission in the intensive care unit and support with
      mechanical ventilation. We discuss the risks potentially associated with the
      reappearance of P. vivax malaria in a previously malaria-free area.

PMID- 24745661
TI  - Evaluation of a pilot national online asthma e-learning program for secondary
      school students.
AB  - BACKGROUND: Ireland has the fourth highest incidence of asthma in the world, with
      Irish children losing on average 10 days of school per annum due to their asthma.
      It is highly probable that a large percentage of students in each class in Irish
      schools have asthma and are required to manage symptoms during the out-of-home
      period. Young people with chronic illnesses such as asthma find themselves
      labelled and marginalized due to a lack of awareness of others about their
      condition. AIMS AND OBJECTIVES: Young people who feel supported by their peers
      have been shown to have higher levels of self-efficacy and fewer exacerbations of
      their asthma symptoms. METHODS: An on-line asthma e-learning program was
      developed to provide support to teenagers who have asthma, and help them inform
      their classmates and friends about asthma. A quasi-experimental approach was used
      to pilot the educational intervention. RESULTS: The results of the pilot
      demonstrate that the program is effective. Teenagers who have asthma found the e
      learning program to be informative and relevant to them. The increase in
      awareness of asthma among teenagers who did not have asthma is shown to influence
      their confidence in assisting their peers who are experiencing asthma symptoms.

PMID- 24745662
TI  - Influence of a municipal solid waste incinerator on ambient air PCDD/F levels: a
      comparison of running and non-running periods.
AB  - The concentration of polychlorinated dibenzo-p-dioxins and dibenzofurans
      (PCDD/Fs) in the ambient air of a municipal solid waste incinerator (MSWI) during
      its running and non-running periods was monitored in this study to investigate
      the contribution of the MSWI to PCDD/F pollution in the vicinal environment.
      Results show that the PCDD/F levels for the normal MSWI running period and after
      shut-down ranged 0.156-1.44 pg I-TEQ/m(3) (0.514 pg I-TEQ/m(3)) and 0.158-0.648
      pg I-TEQ/m(3) (0.345 pg I-TEQ/m(3)), respectively. Significant differences were
      found between the results of the two surveys in 2011 and 2012. High PCDD/F levels
      were observed in two of the seven study sites in 2011, and these levels directly
      declined in 2012. A dramatic increase in PCDD/F concentrations was observed in
      two sites in 2012. Comparison of congener and homologue fingerprint
      characteristics in the two surveys, together with principal component analysis,
      revealed that the PCDD/F levels in all of the samples collected in 2012 and in
      three of the samples collected in 2011 are mainly influenced by heavy traffic.
      MSWI is the primary PCDD/F emission sources of the PCDD/Fs detected in the
      remaining samples collected in 2011.

PMID- 24745663
TI  - Bladder cancer: a portal into men's health.
AB  - Bladder cancer is the fourth most common cancer among men in the United States,
      with a 3-fold higher incidence than women. Globally, tobacco smoking remains
      significantly more common in men, contributing to half of all cases of bladder
      cancer. To prevent bladder cancer, urologists should promote smoking cessation to
      patients presenting at earlier ages with concerns such as sexual dysfunction,
      infertility, pelvic pain, or vasectomy. Bladder cancer also provides an entry
      point for men into the healthcare system, at which time, urologists can discuss
      and coordinate attention to other male health issues such as cardiovascular
      illness, depression, or addiction. By assuming the role of men's health
      physicians, urologists can have a significant benefit on men's urologic and
      overall health by targeting risk factors and behaviors.

PMID- 24745664
TI  - Letter to the editor: The claimed synergistic action of prednisolone and
      cefapirin in mastitis therapy: a comment on Sipka et al. (2013).

PMID- 24745665
TI  - Probiotic viability and storage stability of yogurts and fermented milks prepared
      with several mixtures of lactic acid bacteria.
AB  - Currently, the food industry wants to expand the range of probiotic yogurts but
      each probiotic bacteria offers different and specific health benefits. Little
      information exists on the influence of probiotic strains on physicochemical
      properties and sensory characteristics of yogurts and fermented milks. Six
      probiotic yogurts or fermented milks and 1 control yogurt were prepared, and we
      evaluated several physicochemical properties (pH, titratable acidity, texture,
      color, and syneresis), microbial viability of starter cultures (Lactobacillus
      delbrueckii ssp. bulgaricus and Streptococcus thermophilus) and probiotics
      (Lactobacillus acidophilus, Lactobacillus casei, and Lactobacillus reuteri)
      during fermentation and storage (35 d at 5 degrees C), as well as sensory
      preference among them. Decreases in pH (0.17 to 0.50 units) and increases in
      titratable acidity (0.09 to 0.29%) were observed during storage. Only the yogurt
      with S. thermophilus, L. delbrueckii ssp. bulgaricus, and L. reuteri differed in
      firmness. No differences in adhesiveness were determined among the tested
      yogurts, fermented milks, and the control. Syneresis was in the range of 45 to
      58%. No changes in color during storage were observed and no color differences
      were detected among the evaluated fermented milk products. Counts of S.
      thermophilus decreased from 1.8 to 3.5 log during storage. Counts of L.
      delbrueckii ssp. bulgaricus also decreased in probiotic yogurts and varied from
      30 to 50% of initial population. Probiotic bacteria also lost viability
      throughout storage, although the 3 probiotic fermented milks maintained counts >=
      10(7)cfu/mL for 3 wk. Probiotic bacteria had variable viability in yogurts,
      maintaining counts of L. acidophilus >= 10(7) cfu/mL for 35 d, of L. casei for
      7d, and of L. reuteri for 14 d. We found no significant sensory preference among
      the 6 probiotic yogurts and fermented milks or the control. However, the yogurt
      and fermented milk made with L. casei were better accepted. This study presents
      relevant information on physicochemical, sensory, and microbial properties of
      probiotic yogurts and fermented milks, which could guide the dairy industry in
      developing new probiotic products.

PMID- 24745666
TI  - Safety and tolerability of inhaled loxapine in subjects with asthma and chronic
      obstructive pulmonary disease--two randomized controlled trials.
AB  - BACKGROUND: Loxapine, a first-generation antipsychotic, delivered with a novel
      inhalation delivery device developed for the acute treatment of agitation in
      patients with schizophrenia or bipolar disorder was evaluated in subjects with
      asthma or chronic obstructive pulmonary disease (COPD). METHODS: Separate
      randomized, double-blind, parallel-arm, placebo-controlled trials compared two
      administrations of inhaled loxapine (10 mg) 10 hr apart with placebo in 52
      subjects with asthma and in 53 subjects with COPD. A thermally-generated drug
      aerosol of loxapine was delivered to the deep lung for rapid systemic absorption.
      Controller medications were continued throughout the study, but quick-relief
      bronchodilators were withheld from 6-8 hr before through 34 hr after dose 1,
      unless indicated as rescue. RESULTS: All airway adverse events (AEs) were of mild
      or moderate severity. Symptomatic bronchospasm occurred in 53.8% of subjects with
      asthma after inhaled loxapine and 11.5% after placebo; and in 19.2% of COPD
      subjects after inhaled loxapine and 11.1% after placebo. Subjects required
      inhaled albuterol as follows: asthma: 53.8% after inhaled loxapine and 11.5%
      after placebo; and COPD: 23.1% after inhaled loxapine and 14.8% after placebo.
      Respiratory signs/symptoms requiring treatment responded to rescue bronchodilator
      [forced expiratory volume in 1 sec (FEV(1)) return to within 10% of baseline]
      within 1 hr in 11 of 15 events in asthma subjects and four of seven events in
      COPD subjects, the remainder by the last spirometry. CONCLUSIONS: In subjects
      with either asthma or COPD, FEV(1) decline and bronchospasm can occur following
      inhaled loxapine, but more frequently in asthmatic subjects. Most subjects with
      bronchospasm responded to rescue bronchodilator within 1 hr. No treatment-related
      serious AE occurred. Although inhaled loxapine is contraindicated in patients
      with active airways disease per the current approved US labeling, these studies
      demonstrated that rescue bronchodilator mitigated the symptomatic bronchospasms
      that may occur in case of inadvertent use.

PMID- 24745668
TI  - Effects of dietary n-3 fatty acids and vitamin C on semen characteristics, lipid
      composition of sperm and blood metabolites in fat-tailed Moghani rams.
AB  - Sixteen fertile rams were randomly allotted to four groups and fed either of the
      four diets for 14 weeks: (1) control diet (COD) without fish oil (FO) and vitamin
      C (VC), (2) diet containing 2.5% FO (FOD), (3) diet containing 300 mg/kg DM VC
      (VCD), and (4) diet containing 2.5% FO and 300 mg/kg DM VC (FCD). Semen was
      collected at 14-d intervals from 1 April to 10 July (out of the physiologic
      breeding season in Iran). Semen volume and percentages of motile and
      progressively motile sperm were increased by FO and VC feeding. A significant
      interaction was also found between FOD and VCD on motility and progressive
      motility percentage (P<0.05). HOS-test and percentage of sperm with normal
      acrosome improved significantly by FO and VC. Rams fed FCD had better HOS-test
      and higher proportion of sperm with normal acrosome than rams in other groups
      (82.4 and 93.6%, respectively). Diets containing FO and FO and VC increased the
      proportion of docosahexaenoic acid in sperm (P<0.05). The activity of lactate
      dehydrogenase in the seminal fluid was significantly affected by VC and the
      interaction between FO and VC (P<0.05). Blood metabolites, except glucose, were
      affected positively by FO. The results showed that dietary supplementation with
      FO and VC improved seminal quality and may have beneficial effects on fertility
      in Moghani rams.

PMID- 24745669
TI  - Thinking out of the dish: what to learn about cortical development using
      pluripotent stem cells.
AB  - The development of the cerebral cortex requires the tightly coordinated
      generation of dozens of neuronal subtypes that will populate specific layers and
      areas. Recent studies have revealed how pluripotent stem cells (PSC), whether of
      mouse or human origin, can differentiate into a wide range of cortical neurons in
      vitro, which can integrate appropriately into the brain following in vivo
      transplantation. These models are largely artificial but recapitulate a
      substantial fraction of the complex temporal and regional patterning events that
      occur during in vivo corticogenesis. Here, we review these findings with emphasis
      on the new perspectives that they have brought for understanding of cortical
      development, evolution, and diseases. 

PMID- 24745670
TI  - Diagnostic criteria and classification of mastocytosis in 2014.
AB  - Mastocytosis is characterized by accumulation of pathologic mast cells in
      tissues. Most patients with mastocytosis experience mast cell activation symptoms
      in response to various triggers. The diagnosis of mastocytosis should be made
      from objective pathologic findings. Modern diagnostic criteria and classification
      of mastocytosis were proposed in 2000 by an international consensus group and
      formed the basis of the current World Health Organization (WHO) guidelines, which
      have been validated to correlate with prognosis and help selection of therapy. In
      this article, the WHO criteria for diagnosis and classification are summarized
      and practical aspects to avoid common pitfalls in diagnostic workup are
      discussed. 

PMID- 24745673
TI  - Mast cell-restricted tetramer-forming tryptases and their beneficial roles in
      hemostasis and blood coagulation.
AB  - Tetramer-forming tryptase (hTryptase-beta) was recently discovered to have a
      prominent role in preventing the internal accumulation of life-threatening fibrin
      deposits and fibrin-platelet clots. The anticoagulant activity of hTryptase-beta
      is an explanation for the presence of hemorrhagic disorders in some patients with
      anaphylaxis or mastocytosis. The fragments of hFibrinogen formed by the
      proteolysis of this prominent protein by hTryptase-beta could be used as
      biomarkers in the blood and/or urine for the identification and monitoring of
      patients with mast cell-dependent disorders. Recombinant hTryptase-beta has
      potential to be used in clinical settings where it is desirable to inhibit blood
      coagulation. 

PMID- 24745672
TI  - Molecular defects in mastocytosis: KIT and beyond KIT.
AB  - In all variants of mastocytosis, activating KIT mutations are frequently found.
      In adults, neoplastic mast cells (MCs) cells show the KIT mutation D816V, whereas
      in children, MCs invading the skin are frequently positive for non-KIT D816V
      mutations. The clinical course and prognosis of the disease vary among patients
      with systemic mastocytosis (SM). Additional KIT-independent molecular defects
      might cause progression. Additional oncogenic lesions have recently been
      identified in advanced SM. In advanced SM the presence of additional genetic
      lesions or altered signaling worsening the prognosis might lead to the use of
      alternative therapies such as combined antisignaling targeted treatments or stem
      cell transplantation. 

PMID- 24745674
TI  - Epidemiology, prognosis, and risk factors in mastocytosis.
AB  - This article updates current knowledge about epidemiology, prognosis, and risk
      factors for major complications in mastocytosis. A prevalence of mastocytosis of
      1 in 10000 inhabitants has been reported, but underdiagnosis is assumed. The
      prognosis for cutaneous and indolent systemic mastocytosis is excellent. For more
      advanced forms of disease, prognostic parameters have been identified. A high
      extent of skin involvement, increased basal serum tryptase values, and extensive
      blistering are risk factors for severe mast cell activation episodes in children,
      whereas these associations seem to be less strong or nonexistent for anaphylaxis
      and osteoporosis in adult patients with indolent systemic mastocytosis. 

PMID- 24745671
TI  - Functional deregulation of KIT: link to mast cell proliferative diseases and
      other neoplasms.
AB  - In this review, the authors discuss common gain-of-function mutations in the stem
      cell factor receptor KIT found in mast cell proliferation disorders and summarize
      the current understanding of the molecular mechanisms by which these transforming
      mutations may affect KIT structure and function leading to altered downstream
      signaling and cellular transformation. Drugs targeting KIT have shown mixed
      success in the treatment of mastocytosis and other hyperproliferative diseases. A
      brief overview of the most common KIT inhibitors currently used, the reasons for
      the varied clinical results of such inhibitors and a discussion of potential new
      strategies are provided. 

PMID- 24745675
TI  - Flow cytometry in mastocytosis: utility as a diagnostic and prognostic tool.
AB  - This article presents information for the identification and characterization of
      mast cells from bone marrow and other tissues using multiparametric flow
      cytometry. In addition, it provides guidelines for the application of this
      technique in the subclassification of systemic mastocytosis and assessment of the
      long-term prognosis of patients individually. 

PMID- 24745676
TI  - Mastocytosis: immunophenotypical features of the transformed mast cells are
      unique among hematopoietic cells.
AB  - Mastocytosis is a disease of bone marrow origin histologically characterized by
      compact tissue infiltrates of atypical mast cells never seen in reactive states.
      Most patients with mastocytosis have transformed mast cells carrying an
      activating point mutation at codon 816 of KIT and also show an elevated serum
      tryptase level. In this article immunophenotypical features of mast cells are
      described. Based on these features, mast cells are not closely related to other
      myeloid cells. Using the knowledge on aberrantly expressed antigens by mast
      cells, the hematopathologist should be able to recognize the disease even in the
      presence of unusual morphologic findings or an associated hematologic non-mast
      cell lineage disease. 

PMID- 24745677
TI  - Pathology of extramedullary mastocytosis.
AB  - Mastocytosis encompasses a group of clinically and pathologically heterogeneous
      disorders most commonly involving the skin, which typically takes the form of
      urticaria pigmentosa. Mastocytosis may also involve other organs, most often bone
      marrow, followed by gastrointestinal tract, liver, spleen, and lymph nodes. The
      presence of extracutaneous involvement by mastocytosis is a major diagnostic
      criterion for systemic disease. However, mast cell infiltrates are often subtle
      in skin and extracutaneous organs, and the histologic features of mastocytosis at
      different anatomic sites may be variable. This article reviews the pathologic
      features and clinical correlates of mastocytosis involving skin and other
      extramedullary sites. 

PMID- 24745678
TI  - CD30 in systemic mastocytosis.
AB  - CD30 is a transmembrane receptor, normally not expressed by mast cells, which
      regulates proliferation/apoptosis and antibody responses. Aberrant expression of
      CD30 by mastocytosis mast cells and interaction with its ligand CD30L (CD153)
      appears to play an important role in the pathogenesis and clinical presentation
      of systemic mastocytosis. This article highlights the expression profile and role
      of CD30 and CD30L in physiologic and pathologic conditions, the applicability of
      CD30 as a marker for systemic mastocytosis, the consequences of mast cell
      expressed CD30, and the possibility of future anti-CD30 based cytoreductive
      therapies. 

PMID- 24745679
TI  - Eosinophilia in mast cell disease.
AB  - Eosinophils and mast cells coexist in clonal and nonclonal disorders. The
      interplay between these cells is complex and not fully understood. Discussed are
      both allergic/nonclonal disorders in which both cell types are increased in
      number are likely to play a role in pathogenesis and clonal disorders in which
      both cell types are affected and play key roles in pathogenesis. Finally, some
      treatment options, keeping both disorders in mind, are discussed. Future
      directions in thinking about these disorders are also briefly explored. 

PMID- 24745680
TI  - Epidemiology, diagnosis, and treatment of Hymenoptera venom allergy in
      mastocytosis patients.
AB  - Hymenoptera venom allergy is a typical IgE-mediated reaction caused by
      sensitization to 1 or more allergens of the venom, and accounts for 1.5% to 34%
      of all cases of anaphylaxis. Patients suffering from mastocytosis are more
      susceptible to the anaphylactic reactions to an insect sting. This article aims
      to answer the most important clinical questions raised by the diagnosis and
      treatment of insect venom allergy in mastocytosis patients. Total avoidance of
      Hymenoptera is not feasible, and there is no preventive pharmacologic treatment
      available, although venom immunotherapy reduces the risk of subsequent systemic
      reactions. 

PMID- 24745681
TI  - Bone involvement and osteoporosis in mastocytosis.
AB  - Bone involvement is frequent in patients with systemic mastocytosis. Osteoporosis
      is the most prevalent bone manifestation, but diffuse osteosclerosis or focal
      osteolytic or osteosclerotic lesions are not infrequent. The risk of osteoporotic
      fractures is high, especially at the spine and in men. Routine measurements of
      bone mineral density and vertebral morphometry are warranted. The bone turnover
      markers indicate the involvement of complex bone metabolism in mastocytosis
      related manifestations. Bisphosphonates represent the first-line treatment for
      osteoporosis-related mastocytosis. 

PMID- 24745682
TI  - Drug allergy in mastocytosis.
AB  - Drugs are known triggers of anaphylaxis in patients with mastocytosis even to the
      association between drug anaphylaxis and mastocytosis does not appear frequently
      appear. Nevertheless, mast cell disorders might be ruled out in cases of severe
      systemic reactions. Careful examination of the skin should accompany measurement
      of basal serum tryptase levels. The data published about drug anaphylaxis in
      patients with mast cell disorders are scarce, and it is not currently possible to
      provide clear recommendations. Most papers report cases of anaphylaxis during
      surgical procedures or radiocontrast media exposure. There are no specific
      recommendations to prevent severe reactions during such procedures, although some
      specialists suggest performing premedication with antihistamines and
      corticosteroids before anesthesia or radiocontrast media administration. 

PMID- 24745683
TI  - Neuropsychological features of adult mastocytosis.
AB  - In approximately one-third of cases, patients with mastocytosis can display
      various disabling general and neuropsychological symptoms. General signs may have
      a major impact on quality of life. Neurologic symptoms are less frequent. In a
      majority of cases, the pathophysiology of these symptoms is not known but could
      be linked to tissular mast cell infiltration, mast cell mediator release, or
      both. Treatments aiming at reducing mast cell number and/or stabilizating mast
      cells may be useful. Preliminary results suggest that treatment with kinase
      inhibitors may improve symptoms of depression and cognitive impairment. 

PMID- 24745684
TI  - Mast cell sarcoma: clinical management.
AB  - Mast cell sarcoma is a disorder that results in abnormal mast cells as identified
      by morphology, special stains, and in some publications, c-kit mutation analysis.
      It affects animal species such as canines more commonly than humans. In humans it
      is a very rare condition, with variable clinical presentation. There is no
      standard therapy for the disorder. It can affect any age group. It is
      occasionally associated with systemic mastocytosis and/or urticaria pigmentosa.
      The prognosis of mast cell sarcoma in published literature is very poor in
      humans. 

PMID- 24745685
TI  - Treatment strategies in mastocytosis.
AB  - Treatment recommendations for mastocytosis are based mostly on expert opinion
      rather than evidence obtained from controlled clinical trials. In this article,
      treatment options for mastocytosis are presented, with a focus on the control of
      mediator-related symptoms in patients with indolent disease. 

PMID- 24745686
TI  - The amazing mast cell.

PMID- 24745687
TI  - Mastocytosis.

PMID- 24745688
TI  - Refined OPLS all-atom force field for saturated phosphatidylcholine bilayers at
      full hydration.
AB  - We report parametrization of dipalmitoyl-phosphatidylcholine (DPPC) in the
      framework of the Optimized Parameters for Liquid Simulations all-atom (OPLS-AA)
      force field. We chose DPPC as it is one of the most studied phospholipid species
      and thus has plenty of experimental data necessary for model validation, and it
      is also one of the highly important and abundant lipid types, e.g., in lung
      surfactant. Overall, PCs have not been previously parametrized in the OPLS-AA
      force field; thus, there is a need to derive its bonding and nonbonding
      parameters for both the polar and nonpolar parts of the molecule. In the present
      study, we determined the parameters for torsion angles in the phosphatidylcholine
      and glycerol moieties and in the acyl chains, as well the partial atomic charges.
      In these calculations, we used three methods: (1) Hartree-Fock (HF), (2) second
      order Moller-Plesset perturbation theory (MP2), and (3) density functional theory
      (DFT). We also tested the effect of the polar environment by using the
      polarizable continuum model (PCM), and for acyl chains the van der Waals
      parameters were also adjusted. In effect, six parameter sets were generated and
      tested on a DPPC bilayer. Out of these six sets, only one was found to be able to
      satisfactorily reproduce experimental data for the lipid bilayer. The successful
      DPPC model was obtained from MP2 calculations in an implicit polar environment
      (PCM). 

PMID- 24745689
TI  - Multiplex lateral flow immunoassay for mycotoxin determination.
AB  - A new lateral flow immunoassay (LFA) is proposed for qualitative and/or
      semiquantitative determination of aflatoxin B1 (AFB1), zearalenone (ZEA),
      deoxynivalenol (DON), and their analogues (AFs, ZEAs, DONs) in cereal samples.
      Each of the mycotoxin specific antibody was class specific and there was no cross
      reactivity to other groups of compounds. The visual limits of detection (vLOD) of
      the strip were 0.03, 1.6, and 10 MUg/kg for AFB1, ZEA and DON, respectively. The
      calculated limits of detection (cLOD) were 0.05, 1, and 3 MUg/kg, respectively.
      Meanwhile the cutoff values were achieved at 1, 50, and 60 MUg/kg for AFB1, ZEA
      and DON, respectively. Recoveries ranged from 80% to 122% and RSD from 5% to 20%.
      Both the vLOD and cLOD for the three mycotoxins were lower than the EU maximum
      levels. Analysis of naturally contaminated maize samples resulted in a good
      agreement between the multiplex LFA and LC-MS/MS (100% for DONs and AFs, and 81%
      for ZEAs). Careful analysis of the results further explained the general
      overestimation of LFA compared to chromatographic methods for quantification of
      mycotoxins.

PMID- 24745690
TI  - Sensitivity of the modelled deposition of Caesium-137 from the Fukushima Dai-ichi
      nuclear power plant to the wet deposition parameterisation in NAME.
AB  - This paper describes an investigation into the impact of different meteorological
      data sets and different wet scavenging coefficients on the model predictions of
      radionuclide deposits following the accident at the Fukushima Dai-ichi nuclear
      power plant in March 2011. Three separate operational meteorological data sets,
      the UK Met Office global meteorology, the ECMWF global meteorology and the Japan
      Meteorological Agency (JMA) mesoscale meteorology as well as radar rainfall
      analyses from JMA were all used as inputs to the UK Met Office's dispersion model
      NAME (the Numerical Atmospheric-dispersion Modelling Environment). The model
      predictions of Caesium-137 deposits based on these meteorological models all
      showed good agreement with observations of deposits made in eastern Japan with
      correlation coefficients ranging from 0.44 to 0.80. Unexpectedly the NAME run
      using radar rainfall data had a lower correlation coefficient (R = 0.66), when
      compared to observations, than the run using the JMA mesoscale model rainfall (R
      = 0.76) or the run using ECMWF met data (R = 0.80). Additionally the impact of
      modifying the wet scavenging coefficients used in the parameterisation of wet
      deposition was investigated. The results showed that modifying the scavenging
      parameters had a similar impact to modifying the driving meteorology on the rank
      calculated from comparing the modelled and observed deposition. 

PMID- 24745691
TI  - Influence of amount of starting material for DNA extraction on detection of low
      level presence of genetically engineered traits.
AB  - Two laboratories independently examined how the amount of starting material
      influences DNA extraction efficiency and, ultimately, the detection of low-level
      presence of genetically engineered (GE) traits in commercialized grains. GE
      traits from one maize, two canola, and two soybean samples were used as
      prototypical models in the study design as well as two commonly used DNA
      extraction methods, a small scale (0.1 and 0.2 g samples) and a large scale (1.0
      and 2.0 g samples). The DNA samples were fortified (spiked) at 0.1 and 0.01%
      (w/w) levels. The amount of DNA recovery varied between the two laboratories,
      although a sufficient amount of DNA was obtained to perform replicate PCR
      analysis by both laboratories. Reliable detection of all five events was achieved
      by both laboratories at 0.1% level using either small-scale or large-scale DNA
      extractions. Reliable detection of the GE events was achieved at 0.01% level for
      soybean and canola but not for maize. Variability was observed among the two
      laboratories in terms of the Ct values generated. There was no difference between
      small-scale and large-scale DNA extraction methods for qualitative PCR detections
      of all five GE events. 

PMID- 24745692
TI  - Crenobalneotherapy (spa therapy) in patients with knee and generalized
      osteoarthritis: a post-hoc subgroup analysis of a large multicentre randomized
      trial.
AB  - OBJECTIVE: To determine whether the addition of spa therapy to home exercises
      provides any benefit over exercises and the usual treatment alone in the
      management of generalised osteoarthritis associated with knee osteoarthritis.
      METHODS: This study was a post-hoc subgroup analysis of our randomised
      multicentre trial (www.clinicaltrial.gov: NCT00348777). Participants who met the
      inclusion criteria of generalized osteoarthritis (Kellgren, American College of
      Rheumatology, or Dougados criteria) were extracted from the original randomised
      controlled trial. They had been randomised using Zelen randomisation. The
      treatment group received 18days of spa treatment in addition to a home exercise
      programme. Main outcome was number of patients achieving minimal clinically
      important improvement at six months (MCII) (>=-19.9mm on the VAS pain scale
      and/or >=-9.1 points in a WOMAC function subscale), and no knee surgery.
      Secondary outcomes included the "patient acceptable symptom state" (PASS) defined
      as VAS pain <=32.3mm and/or WOMAC function subscale <=31 points. RESULTS: From
      the original 462 participants, 214 patients could be categorized as having
      generalised osteoarthritis. At sixth month, 182 (88 in control and 94 in SA
      group) patients, were analysed for the main criteria. MCII was observed more
      often in the spa group (n=52/94 vs. 38/88, P=0.010). There was no difference for
      the PASS (n=19/88 vs. 26/94, P=0.343). CONCLUSIONS: This study indicates that spa
      therapy with home exercises may be superior to home exercise alone in the
      management of patients with GOA associated with knee OA.

PMID- 24745693
TI  - Origins of the FIGO initiative to reduce the burden of unsafe abortion.
AB  - The origins of the International Federation of Gynecology and Obstetrics (FIGO)
      Initiative for the Prevention of Unsafe Abortion and its Consequences began in
      1969 when a young British medical student encountered a young woman in Canada
      with complications of unsafe abortion. Through evolving understanding of the
      context of women's lives, including the role of family planning and access to
      safe abortion globally in preventing the deaths and imprisonment of women, I was
      able to contribute to FIGO's advocacy through a collaborative initiative with
      country-led action plans based on a situational analysis. Forty-six member
      associations rapidly agreed to participate with results of situational analyses
      an unprecedented result in FIGO's history. Professor Anibal Faundes' role has
      been pivotal to the success of this initiative, including the establishment of a
      working group of regional coordinators and collaborating agencies to oversee the
      implementation of action plans involving in-country partners and the Ministry of
      Health. Deaths from unsafe abortion and its complications are preventable.

PMID- 24745694
TI  - Introduction of postabortion contraception, prioritizing long-acting reversible
      contraceptives, in the principal maternity hospital of Gabon.
AB  - A prospective, descriptive, analytic study was conducted at the Centre
      Hospitalier de Libreville in Gabon between February and September 2013 to
      evaluate acceptance of long-acting reversible contraceptives (LARC) and depot
      medroxyprogesterone acetate (DMPA) following abortion. Women received counseling
      on the combined oral pill, DMPA, copper intrauterine devices (IUDs), and
      implants. The association between sociodemographic and clinical characteristics,
      knowledge of contraceptives, and acceptance was analyzed. Of the 383 women
      admitted with abortion complications, 206 (53.7%) knew of no systemic
      contraceptives. The best-known method was the oral pill (42.0%). Only 14 women
      (3.6%) knew of a LARC method (IUD or implants) and only 2 (0.5%) said the
      injectable was their best-known method. Over 90% accepted a modern contraceptive
      method after abortion. Two-thirds (66.8%) chose the pill, 14.6% DMPA, and 9.3% a
      LARC method. Only 9.1% of the women refused to initiate use of any method. 

PMID- 24745695
TI  - Contribution of the Central American and Caribbean obstetrics and gynecology
      societies to the prevention of unsafe abortion in the region.
AB  - Unsafe abortion is a very important public health issue in the Central America
      and Caribbean region, where the use of modern contraceptive methods remains low
      and the restrictive legal framework reduces access to safe abortion. The
      International Federation of Gynecology and Obstetrics (FIGO) Initiative for the
      Prevention of Unsafe Abortion and its Consequences is contributing toward
      resolving this problem by strengthening collaboration between medical societies,
      representatives of each country's Ministry of Health, and local and international
      agencies. In the 8 countries that decided to join this initiative in 2008,
      progress has been achieved in improving access to modern contraceptive methods,
      increasing the use of manual vacuum aspiration and misoprostol, and updating
      guidelines on postabortion care. 

PMID- 24745697
TI  - Setting the bar for adjuvant treatment of melanoma.

PMID- 24745696
TI  - Adjuvant bevacizumab in patients with melanoma at high risk of recurrence (AVAST
      M): preplanned interim results from a multicentre, open-label, randomised
      controlled phase 3 study.
AB  - BACKGROUND: Bevacizumab, a monoclonal antibody that targets VEGF, has shown
      restricted activity in patients with advanced melanoma. We aimed to assess the
      role of bevacizumab as adjuvant treatment for patients with resected melanoma at
      high risk of recurrence. We report results from the preplanned interim analysis.
      METHODS: We did a multicentre, open-label, randomised controlled phase 3 trial at
      48 centres in the UK between July 18, 2007, and March 29, 2012. Patients aged 16
      years or older with American Joint Committee on Cancer stage (AJCC) stage IIB,
      IIC, and III cutaneous melanoma were randomly allocated (1:1), via a central,
      computer-based minimisation procedure, to receive intravenous bevacizumab 7.5
      mg/kg, every 3 weeks for 1 year, or to observation. Randomisation was stratified
      by Breslow thickness of the primary tumour, N stage according to AJCC staging
      criteria, ulceration of the primary tumour, and patient sex. The primary endpoint
      was overall survival; secondary endpoints included disease-free interval, distant
      metastases interval and quality of life. Analysis was by intention-to-treat. This
      trial is registered as an International Standardised Randomised Controlled Trial,
      number ISRCTN81261306. FINDINGS: 1343 patients were randomised to either the
      bevacizumab group (n=671) or the observation group (n=672). Median follow-up was
      25 months (IQR 16-37) in the bevacizumab group and 25 months (17-37) in the
      observation group. At the time of interim analysis, 286 (21%) of 1343 enrolled
      patients had died: 140 (21%) of 671 patients in the bevacizumab group, and 146
      (22%) of 672 patients in the observation group. 134 (96%) of patients in the
      bevacizumab group died because of melanoma versus 139 (95%) in the observation
      group. We noted no significant difference in overall survival between treatment
      groups (hazard ratio [HR] 0.97, 95% CI 0.78-1.22; p=0.76); this finding persisted
      after adjustment for stratification variables (HR 1.03; 95% CI 0.81-1.29;
      p=0.83). Median duration of treatment with bevacizumab was 51 weeks (IQR 21-52)
      and dose intensity was 86% (41-96), showing good tolerability. 180 grade 3 or 4
      adverse events were recorded in 101 (15%) of 671 patients in the bevacizumab
      group, and 36 (5%) of 672 patients in the observation group. Bevacizumab resulted
      in a higher incidence of grade 3 hypertension than did observation (41 [6%] vs
      one [<1%]). There was an improvement in disease-free interval for patients in the
      bevacizumab group compared with those in the observation group (HR 0.83, 95% CI
      0.70-0.98, p=0.03), but no significant difference between groups for distant
      metastasis-free interval (HR 0.88, 95% CI 0.73-1.06, p=0.18). No significant
      differences were noted between treatment groups in the standardised area under
      the curve for any of the quality-of-life scales over 36 months. Three adverse
      drug reactions were regarded as both serious and unexpected: one patient had
      optic neuritis after the first bevacizumab infusion, a second patient had
      persistent erectile dysfunction, and a third patient died of a haemopericardium
      after receiving two bevacizumab infusions and was later identified to have had
      significant predisposing cardiovascular risk factors. INTERPRETATION: Bevacizumab
      has promising tolerability. Longer follow-up is needed to identify an effect on
      the primary endpoint of overall survival at 5 years.

PMID- 24745699
TI  - West Nile virus reemergence in Romania: a serologic survey in host species.
AB  - The presence of West Nile virus (WNV) in humans has been known in Romania since
      the 1950s; the 1996 epidemics emphasized the reemergence potential of WNV in
      Romania. Serological surveys made on susceptible species, known as good sentinels
      or reservoir hosts, e.g., horses, wild and domestic birds were undertaken from
      2006-2011. Our results corroborated incidence data in human patients and other
      recent seroprevalence studies in animals, and should partially clarify the
      emergence of WNV in the eastern rural territories of Romania. It also highlighted
      risk zones for endemic WNV infection in Romania.

PMID- 24745698
TI  - Outcomes of adrenal-sparing surgery or total adrenalectomy in phaeochromocytoma
      associated with multiple endocrine neoplasia type 2: an international
      retrospective population-based study.
AB  - BACKGROUND: The prevention of medullary thyroid cancer in patients with multiple
      endocrine neoplasia type 2 syndrome has demonstrated the ability of molecular
      diagnosis and prophylactic surgery to improve patient outcomes. However, the
      other major neoplasia associated with multiple endocrine neoplasia type 2,
      phaeochromocytoma, is not as well characterised in terms of occurrence and
      treatment outcomes. In this study, we aimed to systematically characterise the
      outcomes of management of phaeochromocytoma associated with multiple endocrine
      neoplasia type 2. METHODS: This multinational observational retrospective
      population-based study compiled data on patients with multiple endocrine
      neoplasia type 2 from 30 academic medical centres across Europe, the Americas,
      and Asia. Patients were included if they were carriers of germline pathogenic
      mutations of the RET gene, or were first-degree relatives with histologically
      proven medullary thyroid cancer and phaeochromocytoma. We gathered clinical
      information about patients'RET genotype, type of treatment for phaeochromocytoma
      (ie, unilateral or bilateral operations as adrenalectomy or adrenal-sparing
      surgery, and as open or endoscopic operations), and postoperative outcomes
      (adrenal function, malignancy, and death). The type of surgery was decided by
      each investigator and the timing of surgery was patient driven. The primary aim
      of our analysis was to compare disease-free survival after either adrenal-sparing
      surgery or adrenalectomy. FINDINGS: 1210 patients with multiple endocrine
      neoplasia type 2 were included in our database, 563 of whom had
      phaeochromocytoma. Treatment was adrenalectomy in 438 (79%) of 552 operated
      patients, and adrenal-sparing surgery in 114 (21%). Phaeochromocytoma recurrence
      occurred in four (3%) of 153 of the operated glands after adrenal-sparing surgery
      after 6-13 years, compared with 11 (2%) of 717 glands operated by adrenalectomy
      (p=0.57). Postoperative adrenal insufficiency or steroid dependency developed in
      292 (86%) of 339 patients with bilateral phaeochromocytoma who underwent surgery.
      However, 47 (57%) of 82 patients with bilateral phaeochromocytoma who underwent
      adrenal-sparing surgery did not become steroid dependent. INTERPRETATION: The
      treatment of multiple endocrine neoplasia type 2-related phaeochromocytoma
      continues to rely on adrenalectomies with their associated Addisonian-like
      complications and consequent lifelong dependency on steroids. Adrenal-sparing
      surgery, a highly successful treatment option in experienced centres, should be
      the surgical approach of choice to reduce these complications.

PMID- 24745700
TI  - Impact of oral health conditions on the quality of life of preschool children and
      their families: a cross-sectional study.
AB  - BACKGROUND: Dental caries, traumatic dental injury (TDI) and malocclusion are
      common oral health conditions among preschool children and can have both physical
      and psychosocial consequences. Thus, it is important to measure the impact these
      on the oral health-related quality of life (OHRQoL) of children. The aim of the
      present study was to assess the impact of oral health conditions on the OHRQoL of
      preschool children and their families. METHODS: A preschool-based, cross
      sectional study was carried out with 843 preschool children in the city of
      Campina Grande, Brazil. Parents/caregivers answered the Brazilian Early Childhood
      Oral Health Impact Scale and a questionnaire addressing socio-demographic data as
      well as the parent's/caregiver's perceptions regarding their child's health.
      Clinical exams were performed by three researchers who had undergone a
      calibration process for the diagnosis of dental caries, TDI and malocclusion (K =
      0.83-0.85). Hierarchical Poisson regression was employed to determine the
      strength of associations between oral health conditions and OHRQoL (alpha = 5%).
      The multivariate model was run on three levels obeying a hierarchical approach
      from distal to proximal determinants: 1) socio-demographic data; 2) perceptions
      of health; and 3) oral health conditions. RESULTS: The prevalence of impact from
      oral health conditions on OHRQoL was 32.1% among the children and 26.2% among the
      families. The following variables were significantly associated with a impact on
      OHRQoL among the children: birth order of child (PR = 1.430; 95% CI: 1.045
      1.958), parent's/caregiver's perception of child's oral health as poor (PR =
      1.732; 95% CI: 1.399-2.145), cavitated lesions (PR = 2.596; 95% CI: 1.982-3.400)
      and TDI (PR = 1.413; 95% CI: 1.161-1.718). The following variables were
      significantly associated with a impact on OHRQoL among the families:
      parent's/caregiver's perception of child's oral health as poor (PR = 2.116; 95%
      CI: 1.624-2.757), cavitated lesions (PR = 2.809; 95% CI: 2.009-3.926) and type of
      TDI (PR = 2.448; 95% CI: 1.288-4.653). CONCLUSION: Cavitated lesions and TDI
      exerted a impact on OHRQoL of the preschool children and their families.
      Parents'/caregivers' perception of their child's oral health as poor and the
      birth order of the child were predictors of a greater impact on OHRQoL.

PMID- 24745701
TI  - Objective approach for fending off the sublingual immunotherapy placebo effect in
      subjects with pollenosis: double-blinded, placebo-controlled trial.
AB  - BACKGROUND: Symptom scoring for the assessment of allergen immunotherapy is
      associated with a substantial placebo effect. OBJECTIVE: To assess the ability of
      exhaled breath temperature (EBT), a putative marker of airway inflammation, to
      evaluate objectively the efficacy of grass pollen sublingual immunotherapy in a
      proof-of-concept study. METHODS: This was a double-blinded, placebo-controlled
      clinical trial in 56 subjects (mean +/- SD 30 +/- 12 years old, 33 men)
      sensitized to grass pollen. The objective measurements were EBT, spirometry, and
      periostin and high-sensitivity C-reactive protein in blood. Overall discomfort
      scored on a visual analog scale was used as a proxy for subjective symptoms.
      Evaluations were performed before, during, and after the grass pollen season.
      RESULTS: Fifty-one subjects (25 and 26 in the active treatment and placebo
      groups, respectively) were assessed before and during the pollen season. The mean
      pre- vs in-season increase in EBT was significantly smaller (by 59.1%) in the
      active treatment than in the placebo group (P = .030). Of the other objective
      markers, only the blood periostin level increased significantly during the pollen
      season (P = .047), but without intergroup differences. Subjectively, the mean pre
      vs in-season increase in the visual analog scale score was 32.3% smaller in the
      active treatment than in the placebo group, although this difference did not
      reach statistical significance (P = .116). CONCLUSION: These results suggest that
      the efficacy of grass pollen sublingual immunotherapy can be assessed by EBT, a
      putative quantitative measurement of airway inflammation, which is superior in
      its power to discriminate between active and placebo treatment than a subjective
      assessment of symptoms assessed on a visual analog scale. TRIAL REGISTRATION:
      clinicaltrials.gov Identifier: NCT01785394.

PMID- 24745703
TI  - Introduction to "Medical and surgical advances in hand care: implications for
      hand therapy".

PMID- 24745702
TI  - Effect of vitamin D-binding protein genotype on the development of asthma in
      children.
AB  - BACKGROUND: Potential vitamin D-related influences on inflammatory diseases such
      as asthma are controversial, including the suggestion that vitamin D
      insufficiency is associated with increased asthma morbidity. Vitamin D-binding
      protein transports vitamin D metabolites in the circulation. Single nucleotide
      polymorphisms in the GC gene encoding vitamin D-binding protein are associated
      with circulating vitamin D metabolite levels in healthy infants and toddlers.
      OBJECTIVE: To test the hypothesis that GC single nucleotide polymorphisms
      encoding the D432E and T436K variants predict subsequent development of asthma in
      healthy children. METHODS: A retrospective medical record review was performed to
      determine the development of asthma in 776 children in whom GC genotype, vitamin
      D-binding protein concentration, and circulating 25-hydroxyvitamin D had been
      determined at 6 to 36 months of age. Demographic and detailed current clinical
      data were collected and criteria for asthma were recorded. RESULTS: GC genotype
      was available for 463 subjects. After an initial analysis of all subject data,
      the analysis was limited to the predominant Hispanic population (72.1%) to
      minimize potential confounding effects of ethnicity. Asthma was diagnosed in 87
      children (26%). Subjects with the GC genotype encoding the ET/ET (Gc1s/Gc1s)
      variant had lower odds of developing asthma, representing a protective effect
      compared with subjects with the DT/DT (Gc1f/Gc1f) variant. CONCLUSION: In the
      Hispanic population of inner-city New Haven, Connecticut, the ET/ET (Gc1s/Gc1s)
      genotype of vitamin D-binding protein might confer protection against the
      development of asthma compared with the wild-type genotype DT/DT (Gc1f/Gc1f).

PMID- 24745704
TI  - Bioaccumulation and trophic transfer of short chain chlorinated paraffins in a
      marine food web from Liaodong Bay, North China.
AB  - Short chain chlorinated paraffins (SCCPs) are under the evaluation for inclusion
      into the Stockholm Convention on persistent organic pollutants. However,
      information on their bioconcentration and biomagnification in marine ecosystems
      is unavailable, limiting the evaluation of their ecological risks. In this study,
      seawater, sediment, zooplankton, invertebrates, and fishes collected from
      Liaodong Bay, Bohai Sea, North China were analyzed to investigate the residual
      level, congener group profile, bioaccumulation, and trophic transfer of SCCPs in
      a marine food web. The total concentrations of SCCPs ranged from 4.1 to 13.1 ng
      L(-1) in seawater, 65 to 541 ng g(-1) (dw) in sediment, and 86 to 4400 ng g(-1)
      (ww) in organisms. Correspondence analysis indicated the relative enrichment of
      C10Cl5 and C11Cl5 formula groups in most aquatic organisms. Both the logarithm
      bioaccumulation factors (log BAFs: 4.1-6.7) and biota-sediment accumulation
      factors (BSAFs: 0.1-7.3) of individual congeners implied the bioaccumulation of
      SCCPs. The trophic magnification factor (TMF) of ?SCCPs was determined to be 2.38
      in the zooplankton-shrimp-fish food web, indicating biomagnification potential of
      SCCPs in the marine ecosystem. The TMF values of individual congener groups
      significantly correlated with their log KOW values. 

PMID- 24745705
TI  - Use of programmable versus nonprogrammable shunts in the management of
      hydrocephalus secondary to aneurysmal subarachnoid hemorrhage: a retrospective
      study with cost-benefit analysis.
AB  - OBJECTIVES: The choice of programmable or nonprogrammable shunts for the
      management of hydrocephalus after aneurysmal subarachnoid hemorrhage (SAH)
      remains undefined. Variable intracranial pressures make optimal management
      difficult. Programmable shunts have been shown to reduce problems with drainage,
      but at 3 times the cost of nonprogrammable shunts. METHODS: All patients who
      underwent insertion of a ventriculoperitoneal shunt for hydrocephalus after
      aneurysmal SAH between 2006 and 2012 were included. Patients were divided into
      those in whom nonprogrammable shunts and those in whom programmable shunts were
      inserted. The rates of shunt revisions, the reasons for adjustments of shunt
      settings in patients with programmable devices, and the effectiveness of the
      adjustments were analyzed. A cost-benefit analysis was also conducted to
      determine if the overall cost for programmable shunts was more than for
      nonprogrammable shunts. RESULTS: Ninety-four patients underwent insertion of
      shunts for hydrocephalus secondary to SAH. In 37 of these patients,
      nonprogrammable shunts were inserted, whereas in 57 programmable shunts were
      inserted. Four (7%) of 57 patients with programmable devices underwent shunt
      revision, whereas 8 (21.6%) of 37 patients with nonprogrammable shunts underwent
      shunt revision (p = 0.0413), and 4 of these patients had programmable shunts
      inserted during shunt revision. In 33 of 57 patients with programmable shunts,
      adjustments were made. The adjustments were for a trial of functional improvement
      (n = 21), overdrainage (n = 5), underdrainage (n = 6), or overly sunken skull
      defect (n = 1). Of these 33 patients, 24 showed neurological improvements (p =
      0.012). Cost-benefit analysis showed $646.60 savings (US dollars) per patient if
      programmable shunts were used, because the cost of shunt revision is a lot higher
      than the cost of the shunt. CONCLUSIONS: The rate of shunt revision is lower in
      patients with programmable devices, and these are therefore more cost-effective.
      In addition, the shunt adjustments made for patients with programmable devices
      also resulted in better neurological outcomes.

PMID- 24745706
TI  - Atrophic changes in the trigeminal nerves of patients with trigeminal neuralgia
      due to neurovascular compression and their association with the severity of
      compression and clinical outcomes.
AB  - OBJECT: The aim of this study was to prospectively evaluate atrophic changes in
      trigeminal nerves (TGNs) using measurements of volume (V) and cross-sectional
      area (CSA) from high-resolution 3-T MR images obtained in patients with
      unilateral trigeminal neuralgia (TN), and to correlate these data with patient
      and neurovascular compression (NVC) characteristics and with clinical outcomes.
      METHODS: Anatomical TGN parameters (V and CSA) were obtained in 50 patients (30
      women and 20 men; mean age 56.42 years, range 22-79 years) with classic TN before
      treatment with microvascular decompression (MVD). Parameters were compared
      between the symptomatic (ipsilateralTN) and asymptomatic (contralateralTN) sides
      of the face. Twenty normal control subjects were also included. Two independent
      observers blinded to the side of pain separately analyzed the images.
      Measurements of V (from the pons to the entrance of the nerve into Meckel's cave)
      and CSA (at 5 mm from the entry of the TGN into the pons) for each TGN were
      performed using imaging software and axial and coronal projections, respectively.
      These data were correlated with patient characteristics (age, duration of
      symptoms before MVD, side of pain, sex, and area of pain distribution), NVC
      characteristics (type of vessel involved in NVC, location of compression along
      the nerve, site of compression around the circumference of the root, and degree
      of compression), and clinical outcomes at the 2-year follow-up after surgery.
      Comparisons were made using Bonferroni's test. Interobserver variability was
      assessed using the Pearson correlation coefficient. RESULTS: The mean V of the
      TGN on the ipsilateralTN (60.35 +/- 21.74 mm(3)) was significantly smaller (p <
      0.05) than those for the contralateralTN and controls (78.62 +/- 24.62 mm(3) and
      89.09 +/- 14.72 mm(3), respectively). The mean CSA of the TGN on the
      ipsilateralTN (4.17 +/- 1.74 mm(2)) was significantly smaller than those for the
      contralateralTN and controls (5.41 +/- 1.89 mm(2) and 5.64 +/- 0.85 mm(2),
      respectively). The ipsilateralTN with NVC Grade III (marked indentation) had a
      significantly smaller mean V than the ipsilateralTN with NVC Grade I (mere
      contact), although it was not significantly smaller than that of the
      ipsilateralTN with NVC Grade II (displacement or distortion of root). The
      ipsilateralTN with NVC Grade III had a significantly smaller mean CSA than the
      ipsilateralTN with NVC Grades I and II (p < 0.05). The TGN on the ipsilateralTN
      in cured patients had a smaller mean CSA than that on the ipsilateralTN of
      patients with partial pain relief or treatment failure (p < 0.05). The same
      finding was almost found in relation to measurements of V, but the p value was
      slightly higher at 0.05. CONCLUSIONS: Results showed that TGN atrophy in patients
      with TN can be demonstrated by high-resolution imaging. These data suggest that
      atrophic changes in TGNs, which significantly correlated with the severity of
      compression and clinical outcomes, may help to predict long-term prognosis after
      vascular decompression.

PMID- 24745707
TI  - Low risk for subsequent subarachnoid hemorrhage for emergency department patients
      with headache, bloody cerebrospinal fluid, and negative findings on
      cerebrovascular imaging.
AB  - OBJECT.: When patients present to the emergency department (ED) with acute
      headache concerning for subarachnoid hemorrhage (SAH) and a lumbar puncture (LP)
      shows blood in the CSF, it is difficult to distinguish the results of a traumatic
      LP from those of SAH. CT angiography (CTA) is often performed, but the long-term
      outcome for patients with a positive LP and normal neurovascular imaging remains
      uncertain. The primary objective of this study was to determine whether patients
      who presented to the ED with acute headache and had red blood cells (RBCs) in
      their CSF on LP but negative cerebrovascular imaging suffered subsequent SAH.
      METHODS: A case series study of consecutive adult ED patients who incurred
      charges for LP between 2001 and 2009 was performed from 2010 through 2011.
      Inclusion criteria were: headache, > 5 RBCs/mm(3) in CSF, noncontrast head CT
      with no evidence of hemorrhage, and cerebrovascular CTA or MRA without aneurysm
      or vascular lesion within 2 weeks of the ED visit. Patients with less than 6
      months of available follow-up were excluded. The primary outcomes were 1)
      subsequent nontraumatic SAH and 2) new vascular lesion. Secondary outcomes were
      complications related to SAH, or LP or angiography. RESULTS: Of 4641 ED patients
      billed for an LP, 181 patients (mean age 42 years) were included in this study.
      Over a median follow-up of 53 months, 0 (0%) of 181 patients (95% CI 0%-2.0%) had
      a subsequent SAH or new vascular lesion identified. Although not the primary
      outcome, there was 1 patient who was ultimately diagnosed with vasculitis.
      Eighteen (9.9%) of 181 patients (95% CI 6.0%-15.3%) had an LP-related
      complication and 0 (0%) of 181 patients (95% CI 0%-2.0%) had an angiography
      related complication. CONCLUSIONS: Patients who present to the ED with acute
      headache concerning for SAH and have a finding of bloody CSF on LP but negative
      findings on cerebrovascular imaging are at low risk for subsequent SAH and thus
      are likely to be safe for discharge. Replacement of the CT/LP with a CT/CTA
      diagnostic algorithm merits further investigation.

PMID- 24745708
TI  - Rapid and sensitive intraoperative detection of mutations in the isocitrate
      dehydrogenase 1 and 2 genes during surgery for glioma.
AB  - OBJECT: Intraoperative diagnosis is important in determining the strategies
      during surgery for glioma. Because the mutations in the isocitrate dehydrogenase
      1 and 2 (IDH1 and IDH2) genes have diagnostic, prognostic, and predictive values,
      the authors assessed the feasibility and significance of a simplified method for
      the intraoperative detection of IDH1 and IDH2 gene mutations. METHODS: Rapid DNA
      extraction, amplification with conventional polymerase chain reaction (PCR) or co
      amplification at lower denaturation temperature PCR (COLD-PCR), and fluorescence
      melting curve analysis with adjacent hybridization probes were performed for the
      intraoperative detection of IDH1 and IDH2 mutations in 18 cases of suspected
      nonneoplastic lesions and low- and high-grade gliomas and in 3 cases of radiation
      necrosis. RESULTS: DNA extraction for detection of the mutation took 60-65
      minutes. The results of this assay showed complete correlation with that of
      Sanger sequencing. The sensitivity for detection of mutations in a background of
      wild-type genes was 12.5% and 2.5% in conventional PCR and COLD-PCR,
      respectively. The diagnosis of glioma was established in 3 of 5 cases in which
      definitive diagnosis was not obtained using frozen sections, and information was
      obtained for the discrimination of glioblastoma or glioblastoma with an
      oligodendroglioma component from anaplastic glioma or secondary glioblastoma.
      This assay also detected a small fraction of tumor cells with IDH1 mutation in
      radiation necrosis. CONCLUSIONS: These methods provide important information for
      establishing the differential diagnosis between low-grade glioma and
      nonneoplastic lesions and the diagnosis for subtypes of high-grade glioma.
      Although tumor cells in radiation necrosis were detected with a high sensitivity,
      further investigation is necessary for clinical application in surgery for
      recurrent glioma.

PMID- 24745709
TI  - Pressure autoregulation monitoring and cerebral perfusion pressure target
      recommendation in patients with severe traumatic brain injury based on minute-by
      minute monitoring data.
AB  - OBJECT: In severe traumatic brain injury, a universal target for cerebral
      perfusion pressure (CPP) has been abandoned. Attempts to identify a dynamic CPP
      target based on the patient's cerebrovascular autoregulatory capacity have been
      promising so far. Bedside monitoring of pressure autoregulatory capacity has
      become possible by a number of methods, Czosnyka's pressure reactivity index
      (PRx) being the most frequently used. The PRx is calculated as the moving
      correlation coefficient between 40 consecutive 5-second averages of intracranial
      pressure (ICP) and mean arterial blood pressure (MABP) values. Plotting PRx
      against CPP produces a U-shaped curve in roughly two-thirds of monitoring time,
      with the bottom of this curve representing a CPP range corresponding with optimal
      autoregulatory capacity (CPPopt). In retrospective series, keeping CPP close to
      CPPopt corresponded with better outcomes. Monitoring of PRx requires high
      frequency signal processing. The aim of the present study is to investigate how
      the processing of the information on cerebrovascular pressure reactivity that can
      be obtained from routine minute-by-minute ICP and MABP data can be enhanced to
      enable CPPopt recommendations that do not differ from those obtained by the PRx
      method, show the same associations with outcome, and can be generated in more
      than two-thirds of monitoring time. METHODS: The low-frequency autoregulation
      index (LAx) was defined as the moving minute-by-minute ICP/MABP correlation
      coefficient calculated over time intervals varying from 3 to 120 minutes. The
      CPPopt calculation was based on LAx-CPP plots and done for time windows between 1
      and 24 hours and for each LAx type. The resulting matrix of CPPopts were then
      averaged in a weighted manner, with the weight based on the goodness of fit of a
      U-shape and the lower value of the LAx corresponding to the U-bottom, to result
      in a final CPPopt recommendation. The association between actual CPP/CPPopt and
      outcome was assessed in the multicenter Brain Monitoring with Information
      Technology Research Group (BrainIT) database (n = 180). In the Leuven-Tubingen
      database (60-Hz waveform data, n = 21), LAx- and PRx-based CPPopts were compared.
      RESULTS: In the BrainIT database, CPPopt recommendations were generated in 95% of
      monitoring time. Actual CPP being close to LAx-based CPPopt was associated with
      increased survival. In a multivariate model using the Corticosteroid
      Randomization After Significant Head Injury (CRASH) model as covariates, the
      average absolute difference between actual CPP and CPPopt was independently
      associated with increased mortality. In the high-frequency data set no
      significant difference was observed between PRx-based and LAx-based CPPopts. The
      new method issued a CPPopt recommendation in 97% of monitoring time, as opposed
      to 44% for PRx-based CPPopt. CONCLUSIONS: Minute-by-minute ICP/MABP data contain
      relevant information for autoregulation monitoring. In this study, the authors'
      new method based on minute-by-minute data resolution allowed for CPPopt
      calculation in nearly the entire monitoring time. This will facilitate the use of
      pressure reactivity monitoring in all ICUs.

PMID- 24745710
TI  - Platelet-mediated changes to neuronal glutamate receptor expression at sites of
      microthrombosis following experimental subarachnoid hemorrhage.
AB  - OBJECT: Glutamate is important in the pathogenesis of brain damage after cerebral
      ischemia and traumatic brain injury. Notably, brain extracellular and
      cerebrospinal fluid as well as blood glutamate concentrations increase after
      experimental and clinical trauma. While neurons are one potential source of
      glutamate, platelets also release glutamate as part of their recruitment and
      might mediate neuronal damage. This study investigates the hypothesis that
      platelet microthrombi release glutamate that mediates excitotoxic brain injury
      and neuron dysfunction after subarachnoid hemorrhage (SAH). METHODS: The authors
      used two models, primary neuronal cultures exposed to activated platelets, as
      well as a whole-animal SAH preparation. Propidium iodide was used to evaluate
      neuronal viability, and surface glutamate receptor staining was used to evaluate
      the phenotype of platelet-exposed neurons. RESULTS: The authors demonstrate that
      thrombin-activated platelet-rich plasma releases glutamate, at concentrations
      that can exceed 300 MUM. When applied to neuronal cultures, this activated plasma
      is neurotoxic, and the toxicity is attenuated in part by glutamate receptor
      antagonists. The authors also demonstrate that exposure to thrombin-activated
      platelets induces marked downregulation of the surface glutamate receptor
      glutamate receptor 2, a marker of excitotoxicity exposure and a possible
      mechanism of neuronal dysfunction. Linear regression demonstrated that 7 days
      after SAH in rats there was a strong correlation between proximity to
      microthrombi and reduction of surface glutamate receptors. CONCLUSIONS: The
      authors conclude that platelet-mediated microthrombosis contributes to neuronal
      glutamate receptor dysfunction and might mediate brain injury after SAH.

PMID- 24745711
TI  - Anterior cerebral artery bypass for complex aneurysms: an experience with
      intracranial-intracranial reconstruction and review of bypass options.
AB  - OBJECT: The authors describe their experience with intracranial-to-intracranial
      (IC-IC) bypasses for complex anterior cerebral artery (ACA) aneurysms with giant
      size, dolichoectatic morphology, or intraluminal thrombus; they determine how
      others have addressed the limitations of ACA bypass; and they discuss clinical
      indications and microsurgical technique. METHODS: A consecutive, single-surgeon
      experience with ACA aneurysms and bypasses over a 16-year period was
      retrospectively reviewed. Bypasses for ACA aneurysms reported in the literature
      were also reviewed. RESULTS: Ten patients had aneurysms that were treated with
      ACA bypass as part of their surgical intervention. Four patients presented with
      subarachnoid hemorrhage and 3 patients with mass effect symptoms from giant
      aneurysms; 1 patient with bacterial endocarditis had a mycotic aneurysm, and 1
      patient's meningioma resection was complicated by an iatrogenic pseudoaneurysm.
      One patient had his aneurysm discovered incidentally. There were 2
      precommunicating aneurysms (A1 segment of the ACA), 5 communicating aneurysms
      (ACoA), and 3 postcommunicating (A2-A3 segments of the ACA). In situ bypasses
      were used in 4 patients (A3-A3 bypass), interposition bypasses in 4 patients,
      reimplantation in 1 patient (pericallosal artery-to-callosomarginal artery), and
      reanastomosis in 1 patient (pericallosal artery). Complete aneurysm obliteration
      was demonstrated in 8 patients, and bypass patency was demonstrated in 8
      patients. One bypass thrombosed, but 4 years later. There were no operative
      deaths, and permanent neurological morbidity was observed in 2 patients. At last
      follow-up, 8 patients (80%) were improved or unchanged. In a review of the 29
      relevant reports, the A3-A3 in situ bypass was used most commonly, extracranial
      (EC)-IC interpositional bypasses were the second most common, and reanastomosis
      and reimplantation were used the least. CONCLUSIONS: Anterior cerebral artery
      aneurysms requiring bypass are rare and can be revascularized in a variety of
      ways. Anterior cerebral artery aneurysms, more than any other aneurysms, require
      a thorough survey of patient-specific anatomy and microsurgical options before
      deciding on an individualized management strategy. The authors' experience
      demonstrates a preference for IC-IC reconstruction, but EC-IC bypasses are
      reported frequently in the literature. The authors conclude that ACA bypass with
      indirect aneurysm occlusion is a good alternative to direct clip reconstruction
      for complex ACA aneurysms.

PMID- 24745712
TI  - Endoscopic resection of incidental colloid cysts.
AB  - OBJECT: Incidental colloid cysts are frequently managed with surveillance imaging
      rather than surgical excision. This approach is born out of their purported
      indolent growth pattern and the surgical morbidity associated with microsurgical
      removal. The advent of endoscopic colloid cyst removal may offer renewed
      assessment of these patients who carry a risk of acute neurological
      deterioration. An evidence-based recommendation should weigh the risks of
      operative treatment. Thus far, there has been no concentrated assessment of cyst
      removal in patients with incidental colloid cysts. The major objective in this
      study was to define the risks associated with the endoscopic surgical removal of
      incidentally diagnosed colloid cysts. METHODS: A retrospective review of the
      medical records was performed to search for patients evaluated for a colloid cyst
      between the years 1996 and 2012. Eighty-seven patients underwent colloid cyst
      resection, and 34 were managed with nonoperative surveillance imaging.
      Microsurgical resections, endoscopic resections of residual or recurrent colloid
      cysts, and cases with unknown preoperative symptomatic status were excluded from
      further analysis. Seventy-seven cases of primary endoscopic resections were
      identified. Twenty resections were performed in patients with an incidental
      diagnosis and 57 in symptomatic individuals. Presenting characteristics and
      surgical outcomes were compared between the incidental and symptomatic groups.
      RESULTS: The mean age at surgery was 39.65 years for the incidental and 43.31
      years for the symptomatic group (p = 0.36). The median maximal cyst diameter was
      9.7 mm (range 3-31 mm) for the incidental and 12 mm (range 5-34 mm) for the
      symptomatic group. The mean frontal and occipital horn ratio was 0.3928 for the
      incidental and 0.4445 for the symptomatic group (p = 0.002). Total resection was
      achieved in 90% of the incidental and 82.3% of the symptomatic cases (p = 0.49).
      The median hospital stay was 1 day for incidental and 2 days for symptomatic
      cases (p = 0.006). There were no deaths. There was one case of aseptic meningitis
      in the incidental group. In the symptomatic group there were 3 complications: one
      patient with subjective memory impairment, one with transient short-term memory
      deterioration, and another with a superficial wound infection treated with
      operative debridement. Two patients from the symptomatic group needed a CSF
      diversion procedure, and no shunting was needed in the incidental group. There
      were two recurrences in the symptomatic group (78 and 133 months postoperatively)
      and none in the incidental group (p = 1). CONCLUSIONS: Age and cyst diameter were
      not correlated with the absence or presence of symptoms in patients with a
      colloid cyst of the third ventricle. Operative results were highly favorable in
      both groups and did not reveal a higher risk of morbidity in the patient
      presenting with an incidental lesion. The results support endoscopic resection as
      a legitimate therapeutic option for patients with incidental colloid cysts.
      Generalization of the operative results should be cautiously made, since this is
      a limited series and the results may depend on the degree of neuroendoscopic
      experience.

PMID- 24745713
TI  - In Vivo 3-dimensional corneal epithelial thickness mapping as an indicator of dry
      eye: preliminary clinical assessment.

PMID- 24745714
TI  - Reply: To PMID 24200234.

PMID- 24745715
TI  - The demographic patterns and treatment outcomes of patients with recurrent
      corneal erosions related to trauma and epithelial and bowman layer disorders.

PMID- 24745716
TI  - Reply: To PMID 24075431.

PMID- 24745717
TI  - Pharmacotherapy for restless legs syndrome.
AB  - INTRODUCTION: Restless legs syndrome (RLS) is a common condition characterized by
      paresthesia and an urge to move. Predominantly, symptoms occur at rest in the
      evening or at night, and they are alleviated by moving the affected extremity.
      RLS prevalence in the general population has been estimated to be approximately
      5%. AREAS COVERED: This review presents all options for the treatment of RLS.
      EXPERT OPINION: Pharmacological treatment should be limited to those patients who
      suffer from clinically relevant RLS, that is, when symptoms impair the patient's
      quality of life, daytime functioning, social functioning or sleep. Treatment on
      demand is a clinical need in some RLS patients, and medications include
      carbidopa/levodopa, pramipexole, ropinirole, oxycodone, methadone, codeine and
      tramadol. Chronic RLS should be treated with either a nonergot dopamine agonist
      or an alpha-2-delta calcium channel ligand. A dopamine agonist is a more
      appropriate choice in the presence of depression and overweight. As alpha-2-delta
      ligands can alleviate chronic pain and may be helpful in treating anxiety and
      insomnia, the presence of any of these comorbidities may favor their use. For RLS
      present through much of the day and night, the use of long-acting agents, such as
      the rotigotine patch or gabapentin enacarbil should be considered. In refractory
      RLS, oral prolonged release oxycodone-naloxone should be considered.

PMID- 24745718
TI  - Gills are an initial target of zinc oxide nanoparticles in oysters Crassostrea
      gigas, leading to mitochondrial disruption and oxidative stress.
AB  - The increasing industrial use of nanomaterials during the last decades poses a
      potential threat to the environment and in particular to organisms living in the
      aquatic environment. In the present study, the toxicity of zinc oxide
      nanoparticles (ZnONP) was investigated in Pacific oysters Crassostrea gigas. The
      nanoscale of ZnONP, in vehicle or ultrapure water, was confirmed, presenting an
      average size ranging from 28 to 88 nm. In seawater, aggregation was detected by
      TEM and DLS analysis, with an increased average size ranging from 1 to 2 MUm.
      Soluble or nanoparticulated zinc presented similar toxicity, displaying a LC50
      (96 h) around 30 mg/L. High zinc dissociation from ZnONP, releasing ionic zinc in
      seawater, is a potential route for zinc assimilation and ZnONP toxicity. To
      investigate mechanisms of toxicity, oysters were treated with 4 mg/L ZnONP for 6,
      24 or 48 h. ZnONP accumulated in gills (24 and 48 h) and digestive glands (48 h).
      Ultrastructural analysis of gills revealed electron-dense vesicles near the cell
      membrane and loss of mitochondrial cristae (6 h). Swollen mitochondria and a more
      conspicuous loss of mitochondrial cristae were observed after 24 h. Mitochondria
      with disrupted membranes and an increased number of cytosolic vesicles displaying
      electron-dense material were observed 48 h post exposure. Digestive gland showed
      similar changes, but these were delayed relative to gills. ZnONP exposure did not
      greatly affect thiol homeostasis (reduced and oxidized glutathione) or
      immunological parameters (phagocytosis, hemocyte viability and activation and
      total hemocyte count). At 24 h post exposure, decreased (-29%) glutathione
      reductase (GR) activity was observed in gills, but other biochemical responses
      were observed only after 48 h of exposure: lower GR activity (-28%) and levels of
      protein thiols (-21%), increased index of lipid peroxidation (+49%) and GPx
      activity (+26%). In accordance with ultrastructural changes and zinc load,
      digestive gland showed delayed biochemical responses. Except for a decreased GR
      activity (-47%) at 48 h post exposure, the biochemical alterations seen in gills
      were not present in digestive gland. The results indicate that gills are able to
      incorporate zinc prior (24 h) to digestive gland (48 h), leading to earlier
      mitochondrial disruption and oxidative stress. Our data suggest that gills are
      the initial target of ZnONP and that mitochondria are organelles particularly
      susceptible to ZnONP in C. gigas.

PMID- 24745719
TI  - Unprovoked proximal venous thrombosis is associated with an increased risk of
      asymptomatic pulmonary embolism.
AB  - INTRODUCTION: Pulmonary embolism (PE) is common in patients with deep venous
      thrombosis (DVT). The outcome of DVT with concomitant symptomatic PE is worse
      than the outcome of isolated DVT. The risk factors for DVT and simultaneous
      asymptomatic PE have not been systematically studied yet. AIM: To evaluate the
      frequency and risk factors for asymptomatic PE in patients with DVT.
      PATIENTS/METHODS: In 155 consecutive patients with a first episode of DVT and no
      PE symptoms, a ventilation-perfusion lung scan was performed. Body mass index
      (BMI) and waist-to-hip ratio (WHR) were calculated and concentrations of D-dimer,
      high-sensitivity CRP (hsCRP), tissue plasminogen activator (t-PA) and troponin
      were measured. Laboratory tests for thrombophilia were performed. RESULTS:
      Asymptomatic PE was present in 36% of patients. No differences in gender, age,
      BMI and WHR were found between the patients with and without PE. PE was more
      common in patients with proximal DVT than in those with distal DVT (42% vs. 17%,
      p<0.01), and in patients with unprovoked DVT compared to patients with provoked
      DVT (51% vs. 28%, p<0.01). The risk of silent PE was the highest in patients with
      unprovoked proximal DVT (OR, 6.9; 95% CI, 2.3-21.0). Patients with asymptomatic
      PE had significantly higher values of D-dimer, hsCRP, t-PA and troponin than
      patients with isolated DVT. CONCLUSIONS: Asymptomatic PE affected more than one
      third of patients with a first DVT. Unprovoked proximal DVT is the most important
      risk factor for the occurrence of silent PE.

PMID- 24745720
TI  - Treatment of haemophilia patients in East Germany prior to and after
      reunification in 1990.
AB  - The reunification of Germany in 1990 brought with it major challenges in terms of
      unifying the care offered to haemophilia patients. At that time, most of the
      treatment centres belonged to the largest regional hospitals. The centre for
      paediatric haemophilia patients in Leipzig was at the University Hospital. In
      this centre, early prophylaxis was offered to all patients with severe
      haemophilia A or B. For over 20 years, the treatments of choice in the German
      Democratic Republic were cryoprecipitate for haemophilia A and prothrombin
      complex concentrate for haemophilia B. Cryoprecipitate was relatively effective
      during minor surgery, in cases of mild to moderate bleeding, and for prophylaxis;
      however, unpleasant, relevant side-effects and hepatitis virus transmission were
      frequently encountered in clinical practice. Reunification coincided with the
      availability of virus-safe, high-purity plasma-derived factor VIII concentrates
      (e.g. Beriate((r)) P), which changed the outlook for patients in terms of
      convenience, tolerability, and virus safety; and these new products quickly
      became the treatments of choice for haemophilia A patients at the Leipzig
      Children's Hospital. Today, 20 years later, nearly all of the patients initiated
      on Beriate((r)) P at the time of reunification continue with that treatment, and
      are still benefitting from its excellent efficacy, tolerability, and virus-safety
      profile.

PMID- 24745721
TI  - Clot stability and fibrin deposition is strongly reduced in mice in which mouse
      TAFI is replaced by human TAFI.

PMID- 24745722
TI  - Inhibitors in patients with haemophilia A.
AB  - Inhibitor development is the most problematic and costly complication of
      haemophilia treatment. Inhibitor development depends on a complex multifactorial
      immune response that is influenced by patient- and treatment-related factors.
      Considerable research is focussed on inhibitor development as well as the
      mechanism of eradication through immune tolerance induction (ITI). Once an
      inhibitor develops, two general treatment options are available: to treat acute
      bleeds through bypassing agents, and to eradicate the inhibitor permanently
      through ITI. Previously untreated haemophilia A patients (PUPs) are at greatest
      risk of inhibitor development within the first 20 exposure days to factor VIII
      (FVIII). Inhibitor incidence in PUP studies ranges from 0% to as high as 52%.
      Plasma-derived FVIII concentrates have repeatedly been shown in cohort studies to
      be associated with a decreased inhibitor risk compared with recombinant FVIII
      concentrates, but results from randomized clinical trials are lacking; although
      one such trial is ongoing (SIPPET study). The occurrence of an inhibitor
      represents a major hardship for the patient and his family, and can result in
      high morbidity and a significant reduction in quality of life. Inhibitor
      eradication often requires the need for demanding and expensive treatment
      strategies aimed at inducing immune tolerance or bypassing the inhibitor. The
      role of von Willebrand factor (VWF) in immunoprotection is currently under
      review. The high-purity, pasteurized, plasma-derived FVIII concentrate,
      Beriate((r)), contains sufficient amounts of VWF to not only bind all FVIII
      molecules but also provide additional FVIII binding sites, and may have
      additional beneficial effects that reduce the general immunogenicity of FVIII. 

PMID- 24745723
TI  - Influence of coronary artery disease-associated genetic variants on risk of
      venous thromboembolism.
AB  - INTRODUCTION: We investigated whether genetic variations robustly associated with
      coronary artery disease are also associated with risk of venous thromboembolism
      in a well-defined, female case-control study (n=2753) from Sweden. MATERIALS AND
      METHODS: 39 single nucleotide polymorphisms in 32 loci associated with coronary
      artery disease in genome-wide association studies were identified in a literature
      search and genotyped in the ThromboEmbolism Hormone Study (TEHS). Association
      with venous thromboembolism was assessed by logistic regression. RESULTS: Only
      rs579459 in the ABO locus demonstrated a significant association with VTE. A
      tentative association between ANRIL and VTE in the discovery analysis failed to
      replicate in a meta-analysis of 4 independent cohorts (total n=7181).
      CONCLUSIONS: It appears that only the ABO locus is a shared risk factor for
      coronary artery disease and VTE.

PMID- 24745724
TI  - Molecular pathology curriculum for medical laboratory scientists: A report of the
      association for molecular pathology training and education committee.
AB  - Molecular diagnostics is a rapidly growing specialty in the clinical laboratory
      assessment of pathology. Educational programs in medical laboratory science and
      specialized programs in molecular diagnostics must address the training of
      clinical scientists in molecular diagnostics, but the educational curriculum for
      this field is not well defined. Moreover, our understanding of underlying genetic
      contributions to specific diseases and the technologies used in molecular
      diagnostics laboratories change rapidly, challenging providers of training
      programs in molecular diagnostics to keep their curriculum current and relevant.
      In this article, we provide curriculum recommendations to molecular diagnostics
      training providers at both the baccalaureate and master's level of education. We
      base our recommendations on several factors. First, we considered National
      Accrediting Agency for Clinical Laboratory Sciences guidelines for accreditation
      of molecular diagnostics programs, because educational programs in clinical
      laboratory science should obtain its accreditation. Second, the guidelines of
      several of the best known certifying agencies for clinical laboratory scientists
      were incorporated into our recommendations. Finally, we relied on feedback from
      current employers of molecular diagnostics scientists, regarding the skills and
      knowledge that they believe are essential for clinical scientists who will be
      performing molecular testing in their laboratories. We have compiled these data
      into recommendations for a molecular diagnostics curriculum at both the
      baccalaureate and master's level of education.

PMID- 24745726
TI  - Aspirin for prevention and treatment of venous thromboembolism.
AB  - Venous and arterial thromboses have been regarded for many years as two different
      diseases requiring anticoagulant or antiplatelet treatment, respectively.
      Platelets have a role in venous thromboembolism through several mechanisms,
      including the formation of and adhesion to the neutrophil extracellular traps, as
      recently demonstrated. When given for antithrombotic prophylaxis in high risk
      medical or surgical patients, aspirin was shown to reduce the incidence of venous
      thromboembolism in clinical studies and meta-analyses. However, controversial
      recommendations have been released on the role of aspirin for the prevention of
      venous thromboembolism. Two randomized, double blind trials have recently shown a
      reduction of recurrence by about 30% with aspirin compared to placebo in patients
      who had completed treatment with vitamin K antagonists for a first episode of
      unprovoked venous thromboembolism. The clinical value of this risk reduction in
      comparison to that obtained with warfarin and the new oral anticoagulant agents,
      should take into account the low risk for bleeding and costs associated with
      aspirin. Given its safety, worldwide availability and low cost, aspirin can be
      considered a valid alternative to oral anticoagulants for the extended treatment
      of venous thromboembolism after a first unprovoked event. 

PMID- 24745727
TI  - The use of platelet function testing in PCI and CABG patients.
AB  - Antiplatelet drugs are widely used in the treatment of patients with coronary
      artery disease. Dual anti-platelet therapy with acetylsalicylic acid (ASA) and a
      P2Y12 inhibitor (clopidogrel, prasugrel or ticagrelor) is the recommended
      strategy for patients undergoing a percutaneous coronary intervention (PCI),
      while patients that undergo coronary artery bypass grafting (CABG) are treated
      with ASA monotherapy. However, the response to these drugs as assessed with
      platelet function tests varies between patients. Despite these drugs, many
      patients still exhibit high on-treatment platelet reactivity (HPR), while
      platelet reactivity seems to be excessively inhibited in other patients. This
      review will discuss the use of platelet function testing in the prediction of
      atherothrombotic and bleeding events in patients undergoing PCI or CABG.
      Furthermore, options for tailoring based on platelet function testing in these
      patients are described. 

PMID- 24745728
TI  - Evaluation of the performance of a rapid enzyme-linked immunosorbent assay in the
      detection of Anaplasma phagocytophilum antibodies in horses.
AB  - The aim of this study was to evaluate the performance of a commercially available
      rapid enzyme-linked immonosorbent assay, the Snap(r) 4Dx test, in the detection
      of Anaplasma phagocytophilum antibodies in horses. Two hundred apparently healthy
      horses (asymptomatic) and 244 animals showing clinical symptoms (symptomatic),
      were tested for A. phagocytophilum immunoglobulin G (IgG) antibodies using both
      the Snap(r) 4Dx kit and an indirect fluorescence antibody test (IFAT), with the
      latter serving as a comparative test. Horses belonging to the symptomatic group
      were also tested for evidence of active infection with A. phagocytophilum by
      analysis of IFAT IgM titers and PCR assay amplifying a specific fragment of the
      16S rRNA gene. The overall agreement between the results obtained using the two
      tests, as well as the relative performance exhibited by the Snap(r) 4Dx test in
      the two groups, was assessed. Forty of the 45 animals (89%) testing positive for
      IgG antibodies using IFAT were correctly identified using Snap(r) 4Dx testing.
      The agreement between the results of the two tests was very high (k>0.9), with
      almost identical performances in both symptomatic and asymptomatic animals.
      Conversely, within the symptomatic group, only 44% (no. 11/25) of Snap(r) 4Dx
      positives appeared to be associated with a state of active infection, whereas the
      remaining 56% (no. 14/25) were related both to not infected animals (no. 1) and
      to horses whose status of infection needed further evaluations to be confirmed
      (no. 13/25). This study suggests that the Snap(r) 4Dx test could represent a
      valid screening method for use during epidemiological surveys of equine
      populations. Nevertheless, in-clinic application of the test does not appear to
      be merited.

PMID- 24745729
TI  - Clinical success of intrauterine insemination cycles is affected by the sperm
      preparation time.
AB  - OBJECTIVE: To determine the impact of the time interval from the end of sperm
      preparation (TSP) to intrauterine insemination (IUI) on the outcome. DESIGN:
      Prospective multicentre cohort study. SETTING: Seven French centers (assisted
      reproduction group in northeastern France, four academic centers, and three
      clinics). PATIENT(S): Eight hundred sixty-two IUI cycles (709 patients) managed
      by gonadotropins were studied. INTERVENTION(S): Cycles were stimulated by either
      FSH or hMG, and hCG was administrated when the leading follicle diameter measured
      >15 mm. IUIs were performed ~ 36 hours after ovulation triggering. MAIN OUTCOME
      MEASURE(S): Generalized linear mixed models for binary outcomes were used to
      model clinical pregnancy (CP) to assess the effect of TSP adjusted for other
      predictors (such as maternal age, semen quality, and indication of IUI
      treatment). RESULT(S): The TSP effect was significant, featuring an inverse U
      shaped curve admitting an optimum interval of ~ 40-80 minutes improving CP
      compared with other values. Other significant predictors were total motile
      spermatozoa inseminated, maternal age, and unexplained infertility.
      CONCLUSION(S): The observance of TSP in the range of 40-80 minutes has a
      potential positive effect on pregnancy rate, while not requiring the investment
      of supplemental resources. This finding awaits confirmation in randomized trials.

PMID- 24745730
TI  - Requirement of heart and neural crest derivatives-expressed transcript 2 during
      decidualization of human endometrial stromal cells in vitro.
AB  - OBJECTIVE: To investigate the role of heart and neural crest derivatives
      expressed transcript 2 (HAND2) during decidualization of human endometrial
      stromal cells (ESCs). DESIGN: In vitro experiment. SETTING: Research laboratory.
      PATIENT(S): Twenty-six patients undergoing hysterectomy for benign reasons.
      INTERVENTION(S): ESCs were cultured for 12 days with HAND2 small interfering RNA
      (siRNA) or nonsilencing RNA during decidualization by medroxyprogesterone acetate
      (MPA) and E2. MAIN OUTCOME MEASURE(S): Decidualization was monitored by changes
      in cellular morphology and the expression of several decidual-specific genes.
      RESULT(S): HAND2 siRNA effectively suppressed HAND2 levels in ESCs after 12 days
      of E2 + MPA treatment. ESCs cultured with HAND2 siRNA retained a long fibroblast
      like shape, whereas the cells cultured with control siRNA transformed into
      enlarged polygonal cells. Silencing of HAND2 expression significantly reduced
      connexin-43 involved in the morphologic changes. HAND2 silencing significantly
      reduced the mRNA levels of fibulin-1, prolactin, tissue inhibitor of
      metalloproteinase 3, interleukin-15, and forkhead box O1A (FOXO1A), but had no
      effect on the mRNA levels of dickkopf-1, serum glucocorticoid kinase 1, and
      insulin-like growth factor-binding protein 5. HAND2 siRNA effectively suppressed
      the levels of nuclear FOXO1A protein as a regulator of decidualization.
      CONCLUSION(S): These results suggest that HAND2 plays a key role in the
      regulation of progestin-induced decidualization of human ESCs.

PMID- 24745731
TI  - Molecular detection of bacterial and parasitic pathogens in hard ticks from
      Portugal.
AB  - Ticks are important vector arthropods of human and animal pathogens. As
      information about agents of disease circulating in vectors in Portugal is
      limited, the aim of the present study was to detect bacteria and parasites with
      veterinary and zoonotic importance in ticks collected from dogs, cats, and field
      vegetation. A total of 925 ticks, comprising 888 (96.0%) adults, 8 (0.9%) nymphs,
      and 29 (3.1%) larvae, were collected in 4 geographic areas (districts) of
      Portugal. Among those, 620 (67.0%) were removed from naturally infested dogs, 42
      (4.5%) from cats, and 263 (28.4%) were questing ticks obtained from field
      vegetation. Rhipicephalus sanguineus was the predominant tick species, and the
      only one collected from dogs and vegetation, while all Ixodes ricinus specimens
      (n=6) were recovered from cats. Rickettsia massiliae and Rickettsia conorii were
      identified in 35 ticks collected from cats and dogs and in 3 ticks collected from
      dogs. Among ticks collected from cats or dogs, 4 Rh. sanguineus specimens were
      detected with Hepatozoon felis, 3 with Anaplasma platys, 2 with Hepatozoon canis,
      one with Anaplasma phagocytophilum, one with Babesia vogeli, one with Borrelia
      burgdorferi sensu lato and one with Cercopithifilaria spp. Rickettsia helvetica
      was detected in one I. ricinus tick collected from a cat. To the best of our
      knowledge, this was the first time that Cercopithifilaria spp., Ba. vogeli, H.
      canis, and H. felis have been detected in ticks from Portugal. The wide range of
      tick-borne pathogens identified, some of zoonotic concern, suggests a risk for
      the emergence of tick-borne diseases in domestic animals and humans in Portugal.
      Further studies on these and other tick-borne agents should be performed to
      better understand their epidemiological and clinical importance, and to support
      the implementation of effective control measures.

PMID- 24745732
TI  - DNA interaction probed by evanescent wave cavity ring-down absorption
      spectroscopy via functionalized gold nanoparticles.
AB  - Evanescent wave cavity ring-down absorption spectroscopy (EW-CRDS) is employed to
      study interaction and binding kinetics of DNA strands by using gold nanoparticles
      (Au NPs) as sensitive reporters. These Au NPs are connected to target DNA of
      study that hybridizes with the complementary DNA fixed on the silica surface. By
      the absorbance of Au NPs, the interaction between two DNA strands may be examined
      to yield an adsorption equilibrium constant of 2.2*10(10) M(-1) using Langmuir
      fit. The binding efficiency that is affected by ion concentration, buffer pH and
      temperature is also examined. This approach is then applied to the label-free
      detection of the DNA mutation diseases using the sandwich hybridization assay.
      For monitoring a gene associated with sickle-cell anemia, the detection limit and
      the adsorption equilibrium constant is determined to be 1.2 pM and (3.7+/
      0.8)*10(10) M(-1), distinct difference from the perfectly matched DNA sequence
      that yields the corresponding 0.5 pM and (1.1+/-0.2)*10(11) M(-1). The EW-CRDS
      method appears to have great potential for the investigation of the kinetics of a
      wide range of biological reactions.

PMID- 24745733
TI  - Identification and quantification of carbamate pesticides in dried lime tree
      flowers by means of excitation-emission molecular fluorescence and parallel
      factor analysis when quenching effect exists.
AB  - A non-separative, fast and inexpensive spectrofluorimetric method based on the
      second order calibration of excitation-emission fluorescence matrices (EEMs) was
      proposed for the determination of carbaryl, carbendazim and 1-naphthol in dried
      lime tree flowers. The trilinearity property of three-way data was used to handle
      the intrinsic fluorescence of lime flowers and the difference in the fluorescence
      intensity of each analyte. It also made possible to identify unequivocally each
      analyte. Trilinearity of the data tensor guarantees the uniqueness of the
      solution obtained through parallel factor analysis (PARAFAC), so the factors of
      the decomposition match up with the analytes. In addition, an experimental
      procedure was proposed to identify, with three-way data, the quenching effect
      produced by the fluorophores of the lime flowers. This procedure also enabled the
      selection of the adequate dilution of the lime flowers extract to minimize the
      quenching effect so the three analytes can be quantified. Finally, the analytes
      were determined using the standard addition method for a calibration whose
      standards were chosen with a D-optimal design. The three analytes were
      unequivocally identified by the correlation between the pure spectra and the
      PARAFAC excitation and emission spectral loadings. The trueness was established
      by the accuracy line "calculated concentration versus added concentration" in all
      cases. Better decision limit values (CCalpha), in x0=0 with the probability of
      false positive fixed at 0.05, were obtained for the calibration performed in pure
      solvent: 2.97 MUg L(-1) for 1-naphthol, 3.74 MUg L(-1) for carbaryl and 23.25 MUg
      L(-1) for carbendazim. The CCalpha values for the second calibration carried out
      in matrix were 1.61, 4.34 and 51.75 MUg L(-1) respectively; while the values
      obtained considering only the pure samples as calibration set were: 2.65, 8.61
      and 28.7 MUg L(-1), respectively.

PMID- 24745734
TI  - Data-fusion for multiplatform characterization of an Italian craft beer aimed at
      its authentication.
AB  - Five different instrumental techniques: thermogravimetry, mid-infrared, near
      infrared, ultra-violet and visible spectroscopies, have been used to characterize
      a high quality beer (Reale) from an Italian craft brewery (Birra del Borgo) and
      to differentiate it from other competing and lower quality products. Chemometric
      classification models were built on the separate blocks using soft independent
      modeling of class analogies (SIMCA) and partial least squares-discriminant
      analysis (PLS-DA) obtaining good predictive ability on an external test set (75%
      or higher depending on the technique). The use of data fusion strategies - in
      particular, the mid-level one - to integrate the data from the different
      platforms allowed the correct classification of all the training and validation
      samples. 

PMID- 24745735
TI  - Rapid screening of multiple antibiotic residues in milk using disposable
      amperometric magnetosensors.
AB  - Disposable amperometric magnetosensors, involving a mixture of modified-magnetic
      beads (MBs), for the multiplex screening of cephalosporins (CPHs), sulfonamides
      (SAs) and tetracyclines (TCs) antibiotic residues in milk are reported for the
      first time in this work. The multiplexed detection relies on the use of a mixture
      of target specific modified magnetic beads (MBs) and application of direct
      competitive assays using horseradish peroxidase (HRP)-labeled tracers. The
      amperometric responses measured at -0.20 V vs. the Ag pseudo-reference electrode
      of screen-printed carbon electrodes (SPCE) upon the addition of H2O2 in the
      presence of hydroquinone (HQ) as redox mediator, were used to monitor the extent
      of the different affinity reactions. The developed methodology, involving a
      simple and short pretreatment, allowed discrimination between no contaminated UHT
      and raw milk samples and samples containing antibiotic residues at the maximum
      residue limits (MRLs). The usefulness of the multiplexed magnetosensor was
      demonstrated by analyzing spiked milk samples in only 5 min. The results
      demonstrated that a clear discrimination of milk samples contaminated with
      antibiotics at their MRL level or their mixtures, allowing the identification of
      milk not complying with current legislation. These features make the developed
      methodology a promising alternative in the development of user-friendly devices
      for on-site analysis to ensure quality control for dairy products.

PMID- 24745736
TI  - Evaluation of mycotoxins and their metabolites in human breast milk using liquid
      chromatography coupled to high resolution mass spectrometry.
AB  - Humans can be exposed to mycotoxins through the food chain. Mycotoxins are mainly
      found as contaminants in food and could be subsequently excreted via biological
      fluids such as urine or human breast milk in native or metabolised form. Since
      breast milk is usually supposed as the only food for new-borns, the occurrence of
      mycotoxins in thirty-five human milk samples was evaluated by a newly developed
      method based on QuEChERS extraction and UHPLC-HRMS detection. The method
      described here allows the detection of target mycotoxins in order to determine
      the quality of this initial feeding. The method has been fully validated, with
      recoveries ranging from 64% to 93% and relative standard deviations (RSD, %)
      being lower than 20%. Using the method described, non-metabolised mycotoxins such
      as ZEA, NEO, NIV, ENA, ENA1, ENB, ENB1 and metabolites, such as ZEA metabolites,
      HT-2, DOM and T-2 triol were detected in human milk samples. Results obtained
      help to estimate the exposure of mothers and infants to mycotoxins. Moreover, to
      the best of our knowledge, this is the first work describing the simultaneous
      detection, quantification and screening of mycotoxins and their metabolites in
      human mature milk. 

PMID- 24745737
TI  - Immunoaffinity chromatographic isolation of prostate-specific antigen from
      seminal plasma for capillary electrophoresis analysis of its isoforms.
AB  - Prostate-specific antigen (PSA) concentration in serum has been the biomarker
      employed for prostate cancer diagnosis in the last two decades. However, new more
      specific biomarkers allowing a better differentiation of cancer from non
      malignant prostate diseases are necessary. Glycosylation of PSA gives rise to
      different forms of the protein which can be separated into several isoforms by
      analytical techniques, such as CE. Because PSA glycosylation is influenced by
      pathological conditions, the CE pattern of PSA isoforms could be different in
      prostate cancer than in non-malignant prostate diseases. To study this CE pattern
      of PSA, prior purification of the protein from the biological fluid is mandatory.
      In this study an immunoaffinity chromatography method which allows PSA
      purification without altering the CE pattern is developed. An in-house prepared
      column produced with commercial anti-PSA antibodies is employed. The use of 1 M
      propionic acid as elution agent provides higher than 40% recovery of high purity
      PSA. CE analysis of PSA immunopurified from seminal plasma of a healthy
      individual shows the same 8 peaks as the commercially available PSA standard.
      Sample preparation only requires dilution with phosphate buffered saline prior to
      immunoaffinity purification. High repeatability for the sample preparation step
      was achieved (RSD% for percentage of corrected peak area in the range 0.6-5.3 for
      CE analysis of three independently purified seminal plasma aliquots compared to
      range 0.8-4.9 for a given aliquot analyzed three times by CE). IAC of five
      microliters seminal plasma provided enough PSA to achieve signal/noise ratio
      larger than 5 for the smallest CE isoforms.

PMID- 24745738
TI  - Multi-residue quantification of veterinary drugs in milk with a novel extraction
      and cleanup technique: salting out supported liquid extraction (SOSLE).
AB  - A quantitative liquid chromatography coupled with high-resolution mass
      spectrometry method was developed for the determination of more than one hundred
      compounds belonging to a variety of veterinary drug classes in bovine milk.
      Salting out supported liquid extraction (SOSLE), a novel extraction and cleanup
      technique, was introduced to ensure high extraction efficiency and good sample
      cleanup. The high salt (ammonium sulfate) concentration in the aqueous donor
      phase permits supported liquid/liquid extraction (SLE) with a relative polar
      organic acceptor phase (acetonitrile). This is different from traditional SLE, in
      which the need for phase separation results in the selection of organic solvents
      with intermediate polarities (e.g., ethyl acetate or dichloromethane). Hence,
      SOSLE is more efficient in recovering polar analytes than conventional SLE. SOSLE
      was also compared to classical approaches like solid phase extraction, QuEChERS
      and ultra-filtration. The proposed technique resulted in extracts of equal or
      superior cleanliness and with higher average recoveries than those obtained with
      QuEChERS or SPE. The recovery (median for all compounds) was 73% for QuEChERS,
      83% for SPE and 91% for SOSLE. The most significant improvements were observed
      for polar analytes (penicillines, quinolones and tetracyclines) which are hardly
      recovered by QuEChERS. The chromatographic separation and detection was based on
      an ultra-high-performance liquid chromatography Q-Orbitrap system (Q-Exactive
      plus). The developed analytical method has been validated (based on the
      commission decision 2002/957/EC) as required for quantitative veterinary drug
      methods. 

PMID- 24745739
TI  - An improved approach for flow-based cloud point extraction.
AB  - Novel strategies are proposed to circumvent the main drawbacks of flow-based
      cloud point extraction (CPE). The surfactant-rich phase (SRP) was directly
      retained into the optical path of the spectrophotometric cell, thus avoiding its
      dilution previously to the measurement and yielding higher sensitivity. Solenoid
      micro-pumps were exploited to improve mixing by the pulsed flow and also to
      modulate the flow-rate for retention and removal of the SRP, thus avoiding the
      elution step, often carried out with organic solvents. The heat released and the
      increase of the salt concentration provided by an on-line neutralization reaction
      were exploited to induce the cloud point without an external heating device.
      These innovations were demonstrated by the spectrophotometric determination of
      iron, yielding a linear response from 10 to 200 MUg L(-1) with a coefficient of
      variation of 2.3% (n=7). Detection limit and sampling rate were estimated at 5
      MUg L(-1) (95% confidence level) and 26 samples per hour, respectively. The
      enrichment factor was 8.9 and the procedure consumed only 6 MUg of TAN and 390
      MUg of Triton X-114 per determination. At the 95% confidence level, the results
      obtained for freshwater samples agreed with the reference procedure and those
      obtained for digests of bovine muscle, rice flour, brown bread and tort lobster
      agreed with the certified reference values. The proposed procedure thus shows
      advantages in relation to previously proposed approaches for flow-based CPE,
      being a fast and environmental friendly alternative for on-line separation and
      pre-concentration.

PMID- 24745740
TI  - Total microcystins analysis in water using laser diode thermal desorption
      atmospheric pressure chemical ionization-tandem mass spectrometry.
AB  - A new approach for the analysis of the cyanobacterial microcystins (MCs) in
      environmental water matrices has been developed. It offers a cost efficient
      alternative method for the fast quantification of total MCs using mass
      spectrometry. This approach permits the quantification of total MCs
      concentrations without requiring any derivatization or the use of a suite of MCs
      standards. The oxidation product 2-methyl-3-methoxy-4-phenylbutyric acid (MMPB)
      was formed through a Lemieux oxidation and represented the total concentration of
      free and bound MCs in water samples. MMPB was analyzed using laser diode thermal
      desorption-atmospheric pressure chemical ionization coupled to tandem mass
      spectrometry (LDTD-APCI-MS/MS). LDTD is a robust and reliable sample introduction
      method with ultra-fast analysis time (<15 s sample(-1)). Several oxidation and
      LDTD parameters were optimized to improve recoveries and signal intensity. MCs
      oxidation recovery yield was 103%, showing a complete reaction. Internal
      calibration with standard addition was achieved with the use of 4-phenylbutyric
      acid (4-PB) as internal standard and showed good linearity (R(2)>0.999). Limits
      of detection and quantification were 0.2 and 0.9 MUg L(-1), respectively. These
      values are comparable with the WHO (World Health Organization) guideline of 1 MUg
      L(-1) for total microcystin-LR congener in drinking water. Accuracy and
      interday/intraday variation coefficients were below 15%. Matrix effect was
      determined with a recovery of 91%, showing no significant signal suppression.
      This work demonstrates the use of the LDTD-APCI-MS/MS interface for the
      screening, detection and quantification of total MCs in complex environmental
      matrices.

PMID- 24745741
TI  - Rapid identification of plant materials by wooden-tip electrospray ionization
      mass spectrometry and a strategy to differentiate the bulbs of Fritillaria.
AB  - The counterfeit plant products, especially by using incorrect plant materials in
      pharmaceutical industry, have become a global problem. The plant materials
      belonging to closely related species but differing in medicinal properties are
      difficult to be identified. Here, a novel and generally applicable approach to
      identify the sources of plant materials was developed, which was based on the use
      of wooden-tip electrospray ionization mass spectrometry (wooden-tip ESI-MS) and
      multivariate statistical analysis of unidentified MS features (non-targeted).
      Using this approach, six officinal species of Fritillariae Cirrhosae Bulbus had
      been successfully differentiated. In addition, Fritillariae Pallidiflorae Bulbus,
      a common adulterant of Fritillariae Cirrhosae Bulbus, was also identified by
      using the strategy reported here. Compared with DNA phylogenetic trees, our
      approach provided finer resolution in distinguishing the closely related
      Fritillaria species. By combining wooden-tip ESI-MS and multivariate statistical
      analysis, a useful method was developed here for rapid identification of the
      sources of herbs, which showed promising perspectives in tracking the supply
      chain of pharmaceutical suppliers. 

PMID- 24745742
TI  - Method development for compositional analysis of low molecular weight poly(vinyl
      acetate) by matrix-assisted/laser desorption-mass spectrometry and its
      application to analysis of chewing gum.
AB  - The influence of the sample preparation parameters (the choice of the solvent and
      of the matrix:analyte ratio) was investigated and optimal conditions were
      established for MALDI mass spectrometry analysis of the pristine low molecular
      weight polyvinyl acetate (PVAc). It was demonstrated that comparison of polymer's
      and solvent's Hansen solubility parameters could be used as a guide when choosing
      the solvent for MALDI sample preparation. The highest intensity PVAc signals were
      obtained when ethyl acetate was used as a solvent along with the lowest matrix
      analyte ratio (2,5-dihydroxybenzoic acid was used as a matrix in all
      experiments). The structure of the PVAc was established with high accuracy using
      the matrix-assisted laser desorption/ionization-Fourier transform mass
      spectrometry (MALDI-FTMS) analysis. It was demonstrated that PVAc undergoes
      unimolecular decomposition by losing acetic acid molecules from its backbone
      under the conditions of FTMS measurements. Number and weight average molecular
      weights as well as polydispersity indices were determined with both MALDI-TOF and
      MALDI-FTMS methods. The sample preparation protocol developed was applied to the
      analysis of a chewing gum and the molecular weight and structure of the polyvinyl
      acetate present in the sample were established. Thus, it was shown that optimized
      MALDI mass spectrometry could be used successfully for characterization of
      polyvinyl acetate in commercially available chewing gum. 

PMID- 24745743
TI  - Laminar flow mediated continuous single-cell analysis on a novel
      poly(dimethylsiloxane) microfluidic chip.
AB  - A novel microfluidic chip with simple design, easy fabrication and low cost,
      coupled with high-sensitive laser induced fluorescence detection, was developed
      to provide continuous single-cell analysis based on dynamic cell manipulation in
      flowing streams. Making use of laminar flows, which formed in microchannels,
      single cells were aligned and continuously introduced into the sample channel and
      then detection channel in the chip. In order to rapidly lyse the moving cells and
      completely transport cellular contents into the detection channel, the angle of
      the side-flow channels, the asymmetric design of the channels, and the number,
      shape and layout of micro-obstacles were optimized for effectively redistributing
      and mixing the laminar flows of single cells suspension, cell lysing reagent and
      detection buffer. The optimized microfluidic chip was an asymmetric structure of
      three microchannels, with three microcylinders at the proper positions in the
      intersections of channels. The microchip was evaluated by detection of anticancer
      drug doxorubicin (DOX) uptake and membrane surface P-glycoprotein (P-gp)
      expression in single leukemia K562 cells. An average throughput of 6-8 cells min(
      1) was achieved. The detection results showed the cellular heterogeneity in DOX
      uptake and surface P-gp expression within K562 cells. Our researches demonstrated
      the feasibility and simplicity of the newly developed microfluidic chip for
      chemical single-cell analysis.

PMID- 24745744
TI  - NMR investigation of acrolein stability in hydroalcoholic solution as a
      foundation for the valid HS-SPME/GC-MS quantification of the unsaturated aldehyde
      in beverages.
AB  - Acrolein (propenal) is found in many foods and beverages and may pose a health
      hazard due to its cytotoxicity. Considerable knowledge gaps regarding human
      exposure to acrolein exist, and there is a lack of reliable analytical methods.
      Hydroalcoholic dilutions prepared for calibration purposes from pure acrolein
      show considerable degradation of the compound and nuclear magnetic resonance
      (NMR) spectroscopy showed that 1,3,3-propanetriol and 3-hydroxypropionaldehyde
      are formed. The degradation can be prevented by addition of hydroquinone as
      stabilizer to the calibration solutions, which then show linear concentration
      response behaviour required for quantitative analysis. The stabilized calibration
      solutions were used for quantitative headspace solid-phase microextraction/gas
      chromatography-mass spectrometry (HS-SPME/GC-MS) determination of acrolein in
      alcoholic beverages with a detection limit of 14 MUg L(-1). Of 117 tested
      alcoholic beverages, 64 were tested positive with the highest incidence in grape
      marc spirits and whiskey (100%, mean 252 MUg L(-1)), followed by fruit spirits
      (86%, mean 591 MUg/L(-1)), tequila (86%, mean 404 MUg L(-1)), Asian spirits (43%,
      mean 54 MUg L(-1)) and wine (9%, mean 0.7 MUg L(-1)). Acrolein could not be
      detected in beer, vodka, absinthe and bottled water. Six of the fruit and grape
      marc spirits had acrolein levels above the World Health Organization (WHO)
      provisional tolerable concentration of 1.5 mg L(-1).

PMID- 24745745
TI  - Direct on-strip analysis of size- and time-resolved aerosol impactor samples
      using laser induced fluorescence spectra excited at 263 and 351 nm.
AB  - We report a novel atmospheric aerosol characterization technique, in which dual
      wavelength UV laser induced fluorescence (LIF) spectrometry marries an eight
      stage rotating drum impactor (RDI), namely UV-LIF-RDI, to achieve size- and time
      resolved analysis of aerosol particles on-strip. The UV-LIF-RDI technique
      measured LIF spectra via direct laser beam illumination onto the particles that
      were impacted on a RDI strip with a spatial resolution of 1.2mm, equivalent to an
      averaged time resolution in the aerosol sampling of 3.6 h. Excited by a 263 nm or
      351 nm laser, more than 2000 LIF spectra within a 3-week aerosol collection time
      period were obtained from the eight individual RDI strips that collected
      particles in eight different sizes ranging from 0.09 to 10 MUm in Djibouti. Based
      on the known fluorescence database from atmospheric aerosols in the US, the LIF
      spectra obtained from the Djibouti aerosol samples were found to be dominated by
      fluorescence clusters 2, 5, and 8 (peaked at 330, 370, and 475 nm) when excited
      at 263 nm and by fluorescence clusters 1, 2, 5, and 6 (peaked at 390 and 460 nm)
      when excited at 351 nm. Size- and time-dependent variations of the fluorescence
      spectra revealed some size and time evolution behavior of organic and biological
      aerosols from the atmosphere in Djibouti. Moreover, this analytical technique
      could locate the possible sources and chemical compositions contributing to these
      fluorescence clusters. Advantages, limitations, and future developments of this
      new aerosol analysis technique are also discussed.

PMID- 24745746
TI  - Functionalized carbon dots as sensors for gold nanoparticles in spiked samples:
      formation of nanohybrids.
AB  - This paper reports the synthesis, passivation and functionalization of
      luminescent carbon dots (CDs) possessing surface thiol ending groups. A simple
      procedure involving amidation of passivated carbon dots (p-CDs) with cysteamine
      boosts their photoluminescent properties and enables their use as easily
      controlled fluorescent nanosensors for determining citrate-gold nanoparticles
      (AuNPs). The mechanism behind the quenching phenomenon was established from
      fluorescence measurements at high temperatures and lifetime tests, and found to
      involve static quenching leading to the formation of CD-AuNP nanohybrids. A
      method for determining AuNPs in complex matrices was developed and validated by
      application to spiked drinking water and mussel tissues. The limits of detection
      and quantitation for AuNPs thus obtained were 0.20 and 0.66 nmol L(-1),
      respectively.

PMID- 24745747
TI  - Incorporation of the fluoride induced Si-O bond cleavage and functionalized gold
      nanoparticle aggregation into one colorimetric probe for highly specific and
      sensitive detection of fluoride.
AB  - A highly selective and sensitive probe was developed for the field test of F(-)
      in environmental waters. The probe was fabricated by anchoring 4-mercaptopyridine
      (MPD) on AuNPs via Au-S interaction to form MPD-AuNPs, and further assembling 3
      aminopropyltrimethoxysilane (APTMS) on the surface of MPD-AuNPs. The hydrolysis
      and cross-link of APTMS resulted in a thin monolayer of Si-O-Si protecting layer
      to encapsulated MPD-AuNPs. In the assay, F(-) reacted with Si-O bond and thus
      destroyed the outer protecting layer of the probe, and further triggered the
      aggregation of internal MPD-AuNPs by forming N-H-F hydrogen bond. The F(-)
      induced aggregation of functionalized AuNPs gave rise to significant solution
      color switch from red to blue, which facilitated visual assay of F(-) in the
      range of 1.0-7.0 MUg mL(-1) by naked eyes. The probe is able to discriminate F(-)
      from a wide range of environmentally dominant ions, thus it can be applied to
      detect F(-) in drinkable water with satisfactory results that is agreed well with
      that of using ion chromatography.

PMID- 24745748
TI  - A new fluorescent pH probe for extremely acidic conditions.
AB  - A novel turn-off fluorescent probe based on coumarin and imidazole moiety for
      extremely acidic conditions was designed and developed. The probe with pKa=2.1 is
      able to respond to very low pH value (below 3.5) with high sensitivity relying on
      fluorescence quenching at 460 nm in fluorescence spectra or the ratios of
      absorbance maximum at 380 nm to that at 450 nm in UV-vis spectra. It can
      quantitatively detect pH value based on equilibrium equation, pH=pKa-log[(Ix
      Ib)/(Ia-Ix)]. It had very short response time that was less than 1 min, good
      reversibility and nearly no interference from common metal ions. Moreover, using
      (1)H NMR analysis and theoretical calculation of molecular orbital, we verified
      that a two-step protonation process of two N atoms of the probe leaded to
      photoinduced electron transfer (PET), which was actually the mechanism of the
      fluorescence quenching phenomenon under strongly acidic conditions. Furthermore,
      the probe was also applied to imaging strong acidity in bacteria, E.coli and had
      good effect. This work illustrates that the new probe could be a practical and
      ideal pH indicator for strongly acidic conditions with good biological
      significance.

PMID- 24745749
TI  - Development of a highly sensitive and specific immunoassay for enrofloxacin based
      on heterologous coating haptens.
AB  - In the paper, an enzyme-linked immunosorbent immunoassay (ELISA) for detection of
      enrofloxacin was described using one new derivative of enrofloxacin as coating
      hapten, resulting in surprisingly high sensitivity and specificity. Incorporation
      of aminobutyric acid (AA) in the new derivative of enrofloxacin had decreased the
      IC50 of the ELISA for enrofloxacin from 1.3 MUg L(-1) to as low as 0.07 MUg L(
      1). The assay showed neglect cross-reactivity for other fluoroquinolones but
      ofloxacin (8.23%), marbofloxacin (8.97%) and pefloxacin (7.29%). Analysis of
      enrofloxacin fortified chicken muscle showed average recoveries from 81 to 115%.
      The high sensitivity and specificity of the assay makes it a suitable screening
      method for the determination of low levels of enrofloxacin in chicken muscle
      without clean-up step.

PMID- 24745750
TI  - The gas chromatographic determination of volatile fatty acids in wastewater
      samples: evaluation of experimental biases in direct injection method against
      thermal desorption method.
AB  - The production of short-chained volatile fatty acids (VFAs) by the anaerobic
      bacterial digestion of sewage (wastewater) affords an excellent opportunity to
      alternative greener viable bio-energy fuels (i.e., microbial fuel cell). VFAs in
      wastewater (sewage) samples are commonly quantified through direct injection (DI)
      into a gas chromatograph with a flame ionization detector (GC-FID). In this
      study, the reliability of VFA analysis by the DI-GC method has been examined
      against a thermal desorption (TD-GC) method. The results indicate that the VFA
      concentrations determined from an aliquot from each wastewater sample by the DI
      GC method were generally underestimated, e.g., reductions of 7% (acetic acid) to
      93.4% (hexanoic acid) relative to the TD-GC method. The observed differences
      between the two methods suggest the possibly important role of the matrix effect
      to give rise to the negative biases in DI-GC analysis. To further explore this
      possibility, an ancillary experiment was performed to examine bias patterns of
      three DI-GC approaches. For instance, the results of the standard addition (SA)
      method confirm the definite role of matrix effect when analyzing wastewater
      samples by DI-GC. More importantly, their biases tend to increase systematically
      with increasing molecular weight and decreasing VFA concentrations. As such, the
      use of DI-GC method, if applied for the analysis of samples with a complicated
      matrix, needs a thorough validation to improve the reliability in data
      acquisition. 

PMID- 24745751
TI  - New method for sintering silica frits for capillary microcolumns.
AB  - One of the main steps in the manufacture of robust and efficient packed capillary
      microcolumns for electro- and capillary chromatography is the generation of
      porous devices to retain the packed beds. Frits based on sintered silica
      particles have been found to give the best results in terms of mechanical
      resistance and efficiency. The conventional procedure to produce these kinds of
      frits consists in a radial heating of the packed material with either a flame or
      an electrical resistance, but the frits thus obtained have many drawbacks as a
      result of the procedure rather than the silica per se as the base material. In
      the present work we investigated a new approach to produce silica-based retaining
      devices involving the frontal exposure of a short silica-particle bed packed at
      the end of a capillary tube. The capillary is radially insulated and frontally
      exposed to the heat of a muffle oven, generating a transfer of heat that is not
      radial but rather throughout the capillary axis. This procedure resulted in
      substantial advantages: an improved radial homogeneity, a protection of the
      external polyimide, and a generation of extremely short (400-600 MUm) frits that
      were highly permeable and avoided bubble formation.

PMID- 24745752
TI  - Two-dimensional preparative liquid chromatography system for preparative
      separation of minor amount components from complicated natural products.
AB  - An on-line comprehensive two-dimensional preparative liquid chromatography system
      was developed for preparative separation of minor amount components from
      complicated natural products. Medium-pressure liquid chromatograph (MPLC) was
      applied as the first dimension and preparative HPLC as the second one, in
      conjunction with trapping column and makeup pump. The performance of the trapping
      column was evaluated, in terms of column size, dilution ratio and diameter-height
      ratio, as well as system pressure from the view of medium pressure liquid
      chromatograph. Satisfactory trapping efficiency can be achieved using a
      commercially available 15 mm * 30 mm i.d. ODS pre-column. The instrument
      operation and the performance of this MPLC*preparative HPLC system were
      illustrated by gram-scale isolation of crude macro-porous resin enriched water
      extract of Rheum hotaoense. Automated multi-step preparative separation of 25
      compounds, whose structures were identified by MS, (1)H NMR and even by less
      sensitive (13)C NMR, could be achieved in a short period of time using this
      system, exhibiting great advantages in analytical efficiency and sample treatment
      capacity compared with conventional methods.

PMID- 24745753
TI  - Hybrid carbon nanoparticles modified core-shell silica: a high efficiency carbon
      based phase for hydrophilic interaction liquid chromatography.
AB  - Hydrophilic interaction liquid chromatography (HILIC) is a fast growing
      separation technique for hydrophilic and polar analytes. In this work, we combine
      the unique selectivity of carbon surfaces with the high efficiency of core-shell
      silica. First, 5 MUm core-shell silica is electrostatically coated with 105 nm
      cationic latex bearing quaternary ammonium groups. Then 50 nm anionic carbon
      nanoparticles are anchored onto the surface of the latex coated core-shell silica
      particles to produce a hybrid carbon-silica phase. The hybrid phase shows
      different selectivity than ten previously classified HILIC column chemistries and
      36 stationary phases. The hybrid HILIC phase has shape selectivity for positional
      isomeric pairs (phthalic/isophthalic and 1-naphthoic/2-naphthoic acids). Fast and
      high efficiency HILIC separations of biologically important carboxylates, phenols
      and pharmaceuticals are reported with efficiencies up to 85,000 plates m(-1).
      Reduced plate height of 1.9 (95,000 plates m(-1)) can be achieved. The hybrid
      phase is stable for at least 3 months of usage and storage under typical HILIC
      eluents.

PMID- 24745754
TI  - An experimental design based strategy to optimize a capillary electrophoresis
      method for the separation of 19 polycyclic aromatic hydrocarbons.
AB  - Because of their high toxicity, international regulatory institutions recommend
      monitoring specific polycyclic aromatic hydrocarbons (PAHs) in environmental and
      food samples. A fast, selective and sensitive method is therefore required for
      their quantitation in such complex samples. This article deals with the
      optimization, based on an experimental design strategy, of a cyclodextrin (CD)
      modified capillary zone electrophoresis separation method for the simultaneous
      separation of 19 PAHs listed as priority pollutants. First, using a central
      composite design, the normalized peak-start and peak-end times were modelled as
      functions of the factors that most affect PAH electrophoretic behavior: the
      concentrations of the anionic sulfobutylether-beta-CD and neutral methyl-beta-CD,
      and the percentage of MeOH in the background electrolyte. Then, to circumvent
      computational difficulties resulting from the changes in migration order likely
      to occur while varying experimental conditions, an original approach based on the
      systematic evaluation of the time intervals between all the possible pairs of
      peaks was used. Finally, a desirability analysis based on the smallest time
      interval between two consecutive peaks and on the overall analysis time, allowed
      us to achieve, for the first time in CE, full resolution of all 19 PAHs in less
      than 18 min. Using this optimized capillary electrophoresis method, a vegetable
      oil was successfully analyzed, proving its suitability for real complex sample
      analysis.

PMID- 24745755
TI  - Liposome as a delivery system for carotenoids: comparative antioxidant activity
      of carotenoids as measured by ferric reducing antioxidant power, DPPH assay and
      lipid peroxidation.
AB  - This study was conducted to understand how carotenoids exerted antioxidant
      activity after encapsulation in a liposome delivery system, for food application.
      Three assays were selected to achieve a wide range of technical principles,
      including 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging, ferric reducing
      antioxidant powder (FRAP), and lipid peroxidation inhibition capacity (LPIC)
      during liposome preparation, auto-oxidation, or when induced by ferric
      iron/ascorbate. The antioxidant activity of carotenoids was measured either after
      they were mixed with preformed liposomes or after their incorporation into the
      liposomal system. Whatever the antioxidant model was, carotenoids displayed
      different antioxidant activities in suspension and in liposomes. The
      encapsulation could enhance the DPPH scavenging and FRAP activities of
      carotenoids. The strongest antioxidant activity was observed with lutein,
      followed by beta-carotene, lycopene, and canthaxanthin. Furthermore, lipid
      peroxidation assay revealed a mutually protective relationship: the incorporation
      of either lutein or beta-carotene not only exerts strong LPIC, but also protects
      them against pro-oxidation elements; however, the LPIC of lycopene and
      canthaxanthin on liposomes was weak or a pro-oxidation effect even appeared,
      concomitantly leading to the considerable depletion of these encapsulated
      carotenoids. The antioxidant activity of carotenoids after liposome encapsulation
      was not only related to their chemical reactivity, but also to their
      incorporation efficiencies into liposomal membrane and modulating effects on the
      membrane properties. 

PMID- 24745756
TI  - Immunohistochemical localization of orexin A and orexin type 2 receptor-positive
      cells in the placenta of dogs.
AB  - The aim of the present study was to examine the presence and distribution of
      cells that express immunopositivity for orexin A (OXA) and its type 2 receptor
      (OX2R) in the dog placenta toward the end of pregnancy using immunohistochemical
      techniques. In the placental fetal portion, a few OXA and OX2R-positive cells
      were seen scattered in the outermost coating layer of chorionic villi and in the
      trophoblastic protrusions. Closer to the maternal portion, immunopositive
      labeling for both peptides was visible in the glandular epithelia and that for
      OXA also in the endothelium of the capillaries. These observations allow us to
      hypothesize that the canine placenta may be not only a source of orexin A, but
      also its target, and that orexin A may play an important role in controlling the
      function of this important organ for normal fetal development. 

PMID- 24745757
TI  - Influence of electrical stimulation on calpain and ubiquitin-proteasome systems
      in the denervated and unloaded rat tibialis anterior muscles.
AB  - The influence of electrical stimulation on calpain and ubiquitin-proteasome
      systems was examined in the denervated and unloaded tibialis anterior muscles of
      male Wistar rats. Animals were divided into 5 groups: control, denervation,
      denervation plus electrical stimulation, unloading, and hindlimb unloading plus
      electrical stimulation groups. Due to denervation and unloading for 14 days,
      muscle atrophy markedly occurred in the denervated and unloading animals, and the
      atrophy in the former was significantly more severe than that in the latter. In
      the denervated muscle, the atrophy was significantly attenuated by the electrical
      stimulation, but not in the unloaded muscle. Overexpression of calpain-2 and
      ubiquitinated proteins was observed only in denervated muscles. In the unloaded
      animals, though the expression level of calpain-2 appeared to be slightly higher
      than that in the control, the expression level of ubiquitinated proteins was
      almost the same as that in the control. The overexpression of calpain-1, calpain
      2, and ubiquitinated proteins in the denervated muscle was inhibited by the
      electrical stimulation. However, there was no difference in these expressions
      between the unloaded and unloaded plus electrical stimulation groups. The
      mechanism of the preventive effect of the electrical stimulation on muscle
      atrophy might differ between the denervated and unloaded muscles. 

PMID- 24745759
TI  - Polyphenolics from peach (Prunus persica var. Rich Lady) inhibit tumor growth and
      metastasis of MDA-MB-435 breast cancer cells in vivo.
AB  - The tumor growth inhibition and anti-metastatic effects of peach polyphenolics
      were investigated in vivo using a xenograft model and MDA-MB-435 breast cancer
      cells. Results showed that tumor growth and lung metastasis were inhibited in
      vivo by peach polyphenolics in a dose range of 0.8-1.6 mg/day, and these effects
      were mediated by inhibition of metalloproteinases gene expression. Modulation of
      metalloproteinase-2, metalloproteinase-3 and metalloproteinase-13 gene expression
      may be some of the molecular targets for anti-metastatic activity of peach
      polyphenolics. Therefore, these compounds may constitute a novel chemopreventive
      tool to reduce the risk of metastasis in the combination therapy when primary
      cancer is diagnosed. Conversion to equivalent human intake for future clinical
      studies using the body surface area normalization method gave a dose of ~370.6
      mg/day for a human adult of 60 kg, which can be supplied by consuming two to
      three peach fruit per day or alternatively using a dietary supplement peach
      polyphenol extract powder. 

PMID- 24745760
TI  - Synthesis and characterization of silver(I) pyrazolylmethylpyridine complexes and
      their implementation as metallic silver thin film precursors.
AB  - A series of light- and air-stable silver(I) pyrazolylmethylpyridine complexes
      [Ag(L(R))]n(BF4)n (L = pyrazolylmethylpyridine; R = H, 1; R = Me, 2; R = i-Pr, 3)
      and [Ag(L(R))(NO3)]2 (L = pyrazolylmethylpyridine; R = H, 4; R = Me, 5; R = i-Pr,
      6) has been synthesized and structurally and spectroscopically characterized. In
      all of the molecular structures, the pyrazolylmethylpyridine ligands bridge two
      metal centers, thus giving rise to dinuclear (2, 4, 5, and 6) or polynuclear
      structures (1 and 3). The role played by the counteranions is also of relevance,
      because dimeric structures are invariably obtained with NO3(-) (4, 5, and 6),
      whereas the less-coordinating BF4(-) counteranion affords polymeric structures (1
      and 3). Also, through atoms-in-molecules (AIM) analysis of the electron density,
      an argentophilic Ag...Ag interaction is found in complexes 2 and 4.
      Thermogravimetric analysis (TGA) shows that the thermolytic properties of the
      present complexes can be significantly modified by altering the ligand structure
      and counteranion. These complexes were further investigated as thin silver film
      precursors by spin-coating solutions, followed by annealing at 310  degrees C on
      52100 steel substrates. The resulting polycrystalline cubic-phase Ag films of ~55
      nm thickness exhibit low levels of extraneous element contamination by X-ray
      photoelectron spectroscopy (XPS). Atomic force microscopy (AFM) and scanning
      electron microscopy (SEM) indicate that film growth proceeds primarily via an
      island growth (Volmer-Weber) mechanism. Complex 4 was also evaluated as a
      lubricant additive in ball-on-disk tribological tests. The results of the
      friction evaluation and wear measurements indicate a significant reduction in
      wear (~ 88%) at optimized Ag complex concentrations with little change in
      friction. The enhanced wear performance is attributed to facile shearing of Ag
      metal in the contact region, resulting from thermolysis of the silver complexes,
      and is confirmed by energy-dispersive X-ray analysis of the resulting wear scars.

PMID- 24745758
TI  - NiXantphos: a deprotonatable ligand for room-temperature palladium-catalyzed
      cross-couplings of aryl chlorides.
AB  - Although the past 15 years have witnessed the development of sterically bulky and
      electron-rich alkylphosphine ligands for palladium-catalyzed cross-couplings with
      aryl chlorides, examples of palladium catalysts based on either triarylphosphine
      or bidentate phosphine ligands for efficient room temperature cross-coupling
      reactions with unactivated aryl chlorides are rare. Herein we report a palladium
      catalyst based on NiXantphos, a deprotonatable chelating aryldiphosphine ligand,
      to oxidatively add unactivated aryl chlorides at room temperature. Surprisingly,
      comparison of an extensive array of ligands revealed that under the basic
      reaction conditions the resultant heterobimetallic Pd-NiXantphos catalyst system
      outperformed all the other mono- and bidentate ligands in a deprotonative cross
      coupling process (DCCP) with aryl chlorides. The DCCP with aryl chlorides affords
      a variety of triarylmethane products, a class of compounds with various
      applications and interesting biological activity. Additionally, the DCCP exhibits
      remarkable chemoselectivity in the presence of aryl chloride substrates bearing
      heteroaryl groups and sensitive functional groups that are known to undergo 1,2
      addition, aldol reaction, and O-, N-, enolate-alpha-, and C(sp(2))-H arylations.
      The advantages and importance of the Pd-NiXantphos catalyst system outlined
      herein make it a valuable contribution for applications in Pd-catalyzed arylation
      reactions with aryl chlorides. 

PMID- 24745761
TI  - Interpreting cobalt values after hip replacement: Should we treat the number or
      the patient?

PMID- 24745762
TI  - Leukemoid reaction in sarcomatoid renal cell carcinoma: a two-case report.
AB  - Leukemoid reaction is defined as reactive leukocytosis exceeding 40 * 109/l, with
      a significant increase in early neutrophil precursors, and can be a
      paraneoplastic manifestation of various malignant tumors. Leukemoid reaction is a
      sign for poor prognosis in solid tumors so is sarcomatoid renal cell carcinoma
      (SRCC) when compared to more differentiated histologies. Here, we are reporting
      two cases of leukemoid reaction after radical nephrectomy, both of which were
      diagnosed as SRCC pathologically. The operations were successful: no
      complications were observed and the patients were discharged in good condition.
      However, a few weeks later, the white blood cell (WBC) count gradually increased.
      Even though routine management was done immediately, the count was still
      elevating. A diagnosis of a leukemoid reaction was established and both of them
      died shortly thereafter. Due to the poor prognosis of most patients with
      malignant leukemoid reaction, leukemoid reaction may be a predictor of prognosis
      in patients with SRCC, but more data are needed.

PMID- 24745764
TI  - Protein kinase inhibitors to treat non-small-cell lung cancer.
AB  - INTRODUCTION: Activating mutations of the EGFR and rearrangement of anaplastic
      lymphoma kinase (ALK) best illustrate the therapeutic relevance of molecular
      characterization in NSCLC patients. AREAS COVERED: For this review article, all
      published data on the most relevant Phase III trials with tyrosine kinase
      inhibitors (TKIs) for the treatment of NSCLC were collected and analyzed. EXPERT
      OPINION: Eight Phase III trials clearly established EGFR TKIs as the best
      therapeutic option for front-line therapy in EGFR-mutated patients. In pretreated
      NSCLC, EGFR TKIs are considered more effective than standard monotherapy with
      cytotoxics in presence of classical EGFR mutations, whereas in the EGFR wild-type
      population, a similar efficacy to docetaxel or pemetrexed in term of survival has
      been demonstrated. In ALK-translocated NSCLC, a Phase III trial demonstrated the
      superiority of a multi-target TKI, including ALK, in terms of progression-free
      survival, response rate and toxicity profile when compared to standard second
      line chemotherapy. New agents targeting EGFR or ALK are under evaluation
      particularly in individuals with acquired resistance to EGFR TKIs or crizotinib.

PMID- 24745765
TI  - Is intensive blood pressure lowering justifiable in CKD?

PMID- 24745766
TI  - Molecular investigation for bacterial and protozoan tick-borne pathogens in wild
      boars (Sus scrofa) from southern Germany.
AB  - Wild boars (Sus scrofa) have been suggested to be involved in the enzootic cycle
      of the tick-borne pathogen Anaplasma phagocytophilum. This observation raises the
      question whether they serve as reservoir hosts for A. phagocytophilum and
      potentially for other tick-borne pathogens of public health relevance. The aim of
      this study was to investigate wild boars and their ticks from a forest site in
      southern Germany for the presence of A. phagocytophilum, Candidatus Neoehrlichia
      mikurensis, Rickettsia spp., Borrelia burgdorferi sensu lato (s.l.), Borrelia
      spp. of the relapsing fever group, and Babesia spp. Therefore, 24 wild boars
      collected from October, 2010, to February, 2013, were investigated by molecular
      methods. DNA of A. phagocytophilum was detected in three out of 24 (12.5%) wild
      boars and in four out of 16 (25%) ticks. DNA of none of the other pathogens was
      found in any wild boar, but Rickettsia spp., B. burgdorferi s.l., and Cand. N.
      mikurensis were found in one of the investigated ticks each. Sequences of the
      partial 16S rRNA gene of A. phagocytophilum from one spleen and two ticks showed
      100% similarity to GenBank entries from human anaplasmosis cases (accession nos.
      U02521 and AY886761). The sequence from the third tick was 100% similar to
      sequences obtained from Ixodes ricinus and roe deer from the same study area
      previously. Detecting a potentially human pathogenic A. phagocytophilum variant
      in wild boar confirms previous findings and is of public health interest. To our
      knowledge, this is the first report of A. phagocytophilum in wild boars in
      Germany. Whether wild boars support the enzootic cycle of A. phagocytophilum
      variants involved in human disease requires further attention in future
      systematic studies.

PMID- 24745767
TI  - The effect of kyphoscoliosis on intervertebral disc degeneration in dogs.
AB  - In people, abnormalities in vertebral column conformation, such as
      kyphoscoliosis, induce degenerative changes in adjacent intervertebral disc (IVD)
      structure and composition. It was hypothesised that canine IVDs adjacent to a
      vertebral malformation undergo early degeneration. In a blinded retrospective
      study, thoracic IVD degeneration was evaluated in 14 dogs on magnetic resonance
      images using Pfirrmann's grade. IVDs adjacent to a vertebral malformation had
      higher grades of degeneration than non-adjacent IVDs (P < 0.0001). There was an
      age-dependency, with dogs between 1 and 4 years showing higher grade of
      degeneration in adjacent than non-adjacent IVDs (P < 0.0001). Conversely, in
      older dogs, all IVDs - including the non-adjacents - showed degenerative signs,
      possibly due to normal aging. These results suggest that congenital vertebral
      malformation results in early degeneration of adjacent IVDs.

PMID- 24745769
TI  - Nuclear pleomorphism: role in grading and prognosis of canine mammary carcinomas.
AB  - Canine mammary tumours are highly heterogeneous in morphology and behaviour and
      successful clinical management requires robust prognostic factors. Histological
      grade, determined by the Nottingham nuclear pleomorphism scoring method, has been
      considered one of these factors. Despite the adoption of this method, it is
      unknown whether inter-observer agreement exists regarding the assessment of its
      parameters in canine mammary carcinomas (CMC). In this study, the agreement
      between two observers in scoring nuclear pleomorphism using the Nottingham method
      was evaluated in 89 cases of CMC. Histological evidence of vascular invasion
      and/or lymph node metastases (both early signs of tumour aggressiveness) was
      recorded. For 48 animals, two years of follow-up data were available. Nuclear
      pleomorphism was quantitatively assessed using a stereological method that
      allowed for an unbiased estimation of nuclear size and its variability by
      determining the volume-weighted mean nuclear volume (v-v). Differences between
      the v-v estimations and nuclear pleomorphism scores were evaluated. Additionally,
      the prognostic significance of clinicopathological features including nuclear
      score and v-v was evaluated. A poor agreement between the two observers was
      obtained (kappa value 0.46). Tumours scored as 1 and 2 presented similar v-v
      values and only tumours that scored 3 presented significantly higher estimates.
      The v-v value was not associated with vascular invasion and/or lymph node
      metastases, but was higher in tumours that progressed during follow-up. In
      multivariable analysis, only tumour size was an independent factor regarding
      evidence of aggressiveness and an optimal cut-off of 2.9 cm was defined.

PMID- 24745768
TI  - Expression of 11beta-hydroxysteroid dehydrogenase isoforms in canine adrenal
      glands treated with trilostane.
AB  - Trilostane, a competitive inhibitor of 3beta-hydroxysteroid dehydrogenase, is
      often used to treat canine hyperadrenocorticism. In some species, trilostane has
      been shown to have additional effects on steroid biosynthesis, and it has been
      postulated that trilostane might have effects on 11beta-hydroxysteroid
      dehydrogenase (11beta-HSD) in dogs. To investigate the effect of trilostane on
      11beta-HSD in canine adrenal glands, healthy Beagle dogs were treated with
      trilostane for 8 weeks. Trilostane treatment resulted in a significant decrease
      of the cortisol/cortisone ratio in the serum. The adrenal gland mRNA and protein
      expression levels of 11beta-HSD type 1 and 11beta-HSD type 2 were significantly
      higher and significantly lower respectively in dogs treated with trilostane
      compared to those in control healthy Beagle dogs. These findings suggest that
      trilostane may have an effect on 11beta-HSD activity in canine adrenal glands.

PMID- 24745770
TI  - Immunohistochemical evaluation of tissue factor, fibrin/fibrinogen and D-dimers
      in canine gliomas.
AB  - In human gliomas, tissue factor (TF) is overexpressed, associated with the grade
      of malignancy and influences tumour biology. Intra-tumoural fibrin/fibrinogen
      deposition and activation of the fibrinolytic system also play a role in tumour
      cell proliferation and angiogenesis. The first aim of the present study was to
      investigate TF expression and the presence of fibrin/fibrinogen and D-dimers in
      canine glioma biopsies, graded according to the World Health Organization (WHO)
      classification of tumours of the central nervous system. The second aim was to
      investigate the occurrence of intravascular thrombosis (IVT) in canine gliomas,
      as a potential histological marker of glioma type or grade of malignancy. An
      immunohistochemical study using antibodies against TF, fibrin/fibrinogen and D
      dimers was performed with 24 glioma samples, including 15 oligodendrogliomas, 6
      astrocytomas and 3 mixed gliomas. Immunohistochemical data were statistically
      analysed to determine whether there was any relationship between glioma type and
      grade of malignancy. All gliomas were moderate to strongly positive for TF and
      the staining score was significantly higher (P = 0.04) in high-grade (III or IV)
      than in low-grade (II) gliomas. Intra-tumoural fibrin/fibrinogen deposition was
      detected in all tumour biopsies assessed, and D-dimers were detected in 17/24
      gliomas. IVT was a frequent finding, but was not linked to a specific glioma type
      or malignancy grade. TF expression, fibrin/fibrinogen deposition, extravascular
      fibrinolytic system activation and IVT occur in canine gliomas. Canine glioma
      might be a suitable model for studying coagulation and fibrinolysis as potential
      therapeutic targets for human gliomas.

PMID- 24745771
TI  - Use of tyrosyl bolaamphiphile self-assembly as a biochemically reactive support
      for the creation of palladium catalysts.
AB  - The self-assembly of tyrosine-containing bolaamphiphile was applied as a catalyst
      support on which palladium (Pd) catalysts were loaded to exploit the biochemical
      activity of tyrosine. The bolaamphiphile self-assembled to form spherical
      structures exposing tyrosine moieties on the surface. The phenyl group of
      tyrosine was then used to create the Pd catalyst on the spherical self-assembly.
      Silver (Ag) clusters were decorated on the surface, exploiting the reducing
      function of the phenyl group. These Ag clusters were further applied to create Pd
      catalysts through the galvanic replacement reaction in the next step. The
      produced Pd catalyst showed reliable catalytic activity in decomposing dichromate
      with a pseudo-first-order reaction rate. The reaction rate constant increased
      proportionally to the Pd loading on the self-assembly support. In addition, as a
      solid support, the bolaamphiphile self-assembly made catalyst recovery easy, and
      the recovered Pd catalysts showed consistent activity after several cycles. The
      experimental results demonstrated that the bolaamphiphile self-assembly is a
      promising organic support with biochemical activity for the facile creation of
      metallic catalysts. 

PMID- 24745772
TI  - Overt small-intestine bleeding caused by Ancylostoma duodenale.

PMID- 24745773
TI  - The "comfortable dying" measure: how patient characteristics affect hospice pain
      management quality scores.
AB  - BACKGROUND: All hospices were required by the Centers for Medicare and Medicaid
      Services (CMS) to collect the "Comfortable Dying" measure in 2012 (National
      Quality Forum measure #0209). However, it is not known how scores on this measure
      are affected by patient characteristics. It is important to identify these
      characteristics so that a hospice's case mix can be taken into account when
      interpreting its scores. OBJECTIVE: Our aim was to describe the implementation of
      the NQF #0209 measure in 10 hospices and to identify patient characteristics
      associated with scores. METHODS: We conducted an electronic health record (EHR)
      based retrospective cohort study of patients in 10 hospices in the United States.
      The main outcome measure was the proportion of patients with pain that made them
      uncomfortable whose pain was controlled within 48 hours. RESULTS: A total of 4157
      patients were eligible for an initial pain assessment. Of those who reported pain
      (n=1992), 1152 (58%) reported having their pain controlled on the follow-up
      assessment. In a multivariable regression model, clustered by hospice, six
      variables were independently associated with pain control. These included age
      (adjusted odds ratio [OR] 1.02; 95% confidence interval [CI] 1.02-1.03, p=0.003),
      a cancer diagnosis (OR 1.37; 95% CI 1.20-1.53, p=0.008), initial care in an
      inpatient unit (OR 1.28; 95% CI 1.08-1.47, p=0.031), presence of a Foley catheter
      (OR 1.40; 95% CI 1.15-1.59, p=0.038), use of opioid medication (OR 1.34; 95% CI
      1.03-1.74, p=0.027), and higher Palliative Performance Scale (PPS) score (OR
      1.02; 95% CI 1.01-1.03, p<0.001). Presence of a Stage 2 pressure ulcer was
      independently associated with worse pain control (OR 0.63; 95% CI 0.31-0.96,
      p=0.012). CONCLUSIONS: Several patient characteristics are associated with #0209
      pain scores. As hospices are increasingly required to report quality measures, it
      will be essential to understand how their scores are affected by case mix.

PMID- 24745774
TI  - Effectiveness of mindfulness-based stress reduction and mindfulness based
      cognitive therapy in vascular disease: A systematic review and meta-analysis of
      randomised controlled trials.
AB  - OBJECTIVE: To determine the effectiveness of mindfulness-based stress reduction
      (MBSR) and mindfulness-based cognitive therapy (MBCT) on psychological and
      physical outcomes for people with vascular disease. DESIGN: Systematic review and
      meta-analysis of randomised controlled trials. DATA SOURCES: AMED, CINAHL,
      EMBASE, British Nursing Index, Medline, Web of Science, PsycINFO, Cochrane
      Database of Systematic Reviews, Central, Social Sciences Citation Index, Social
      Policy and Practice, and HMIC from inception to January 2013. REVIEW METHODS:
      Articles were screened for inclusion independently by two reviewers. Data
      extraction and quality appraisal were performed by one reviewer and checked by a
      second with discrepancies resolved by discussion with a third if necessary.
      Random-effects meta-analyses were performed. RESULTS: Nine articles (from eight
      original randomised controlled trials) met eligibility criteria and were included
      in the final review. In total, 578 participants were enrolled across the trials,
      with participants presenting with prehypertension/hypertension (n=3 trials), type
      1 or 2 diabetes (n=2), heart disease (n=2) and stroke (n=1). Meta-analyses, using
      standardised mean differences, showed evidence of reductions in stress (-0.36;
      95% CI -0.67 to -0.09; p=0.01), depression (-0.35; 95% CI -0.53 to -0.16;
      p=0.003) and anxiety (-0.50; 95% CI -0.70 to -0.29; p<0.001). Effects on physical
      outcomes (blood pressure, albuminuria, stress hormones) were mixed. CONCLUSION:
      Whilst populations with vascular disease appear to derive a range of
      psychological benefits from MBSR/MBCT intervention, the effects on physical
      parameters of disease are not yet established. More robust studies, with longer
      term follow-up, are required to ascertain full effectiveness of such
      intervention.

PMID- 24745775
TI  - Suicide risk in type 1 diabetes mellitus: A systematic review.
AB  - BACKGROUND: Research has shown that suicide risk is often present in patients
      suffering from type 1 diabetes mellitus (DM-1). OBJECTIVES: The aim of the
      present paper was to investigate whether there was a relationship between DM-1
      and suicidal behavior and to determine whether or not people affected by DM-1 are
      at an increased risk of completed suicide, attempted suicide, and suicidal
      ideation. DATA SOURCES: We performed a careful MedLine, ExcerptaMedica, PsycLit,
      PsycInfo and Index Medicus search to identify all papers on the topic for the
      period 1970 to 2013 written in English. The following search terms were used:
      (suicide OR suicide attempt OR ideation) AND (diabetes mellitus). Where a title
      or abstract seems to describe a study eligible for inclusion, the full article
      was examined. ELIGIBILITY CRITERIA: We included only original articles published
      in English peer-reviewed journals. We excluded meta-analyses and systematic
      reviews, studies that were not clear about follow-up times, the method of
      statistical analysis, diagnostic criteria or the number of patients included, and
      studies only on patients affected by type 2 diabetes mellitus (DM-2). RESULTS:
      The research reviewed indicated that patients with DM-1 are at an increased risk
      for suicide, although no clear consensus exists regarding the level of the
      increased risk. LIMITATIONS: The studies used different measurement techniques
      and different outcomes, and they assessed patients at different time points.
      CONCLUSIONS AND IMPLICATIONS: Our findings support the recommendation that a
      suicide risk assessment of patients with DM-1 should be part of the routine
      clinical assessment. The assessment of patients at risk should consist of the
      evaluation of current and previous suicidal behaviors (both suicidal ideation and
      attempted suicide).

PMID- 24745776
TI  - Sleep-wake misperception in sleep apnea patients undergoing diagnostic versus
      titration polysomnography.
AB  - OBJECTIVE: Insomnia is commonly co-morbid with obstructive sleep apnea. Among
      patients reporting insomnia symptoms, sleep misperception occurs when self
      reported sleep duration under-estimates objective measures. Misperception
      represents a clinical challenge since insomnia management is based entirely on
      patient self-report. We tested the hypothesis that misperception occurring in
      sleep apnea patients would improve with subsequent treatment. METHODS: We
      compared subjective sleep-wake reports with objective sleep in adults with
      obstructive sleep apnea (n=405) in two nights of polysomnography (diagnostic and
      treatment) within a median interval of 92 days. RESULTS: Sleep latency was
      generally over-estimated, while wake after sleep onset and number of awakenings
      were under-estimated. None of these estimations differed between diagnostic and
      treatment polysomnograms. We observed a large spectrum of total sleep time
      misperception values during the diagnostic polysomnogram, with one third of the
      cohort under-estimating their total sleep time by at least 60 min. Of those with
      >60 minute misperception, we observed improved total sleep time perception during
      treatment polysomnography. Improved perception correlated with improvements in
      self-reported sleep quality and response confidence. We found no polysomnogram or
      demographic predictors of total sleep time misperception for the diagnostic
      polysomnogram, nor did we find objective correlates of improved perception during
      titration. CONCLUSION: Our results suggest that misperception may improve with
      treatment of obstructive sleep apnea in patients who also exhibit misperception.
      Within subject changes in misperception are consistent with misperception being,
      at least to some extent, a state characteristic, which has implications for
      management of patients with comorbid insomnia and sleep apnea.

PMID- 24745778
TI  - Validity and reliability of the Brief Insomnia Questionnaire in the general
      population in Hong Kong.
AB  - OBJECTIVES: The Brief Insomnia Questionnaire (BIQ) was first validated in the
      U.S. for insomnia disorders according to the Diagnostic and Statistical Manual,
      Fourth Edition, Text Revision (DSM-IV-TR), International Classification of
      Diseases, Tenth Edition (ICD-10) and research diagnostic criteria/International
      Classification of Sleep Disorders, Second Edition (RDC/ICSD-2). We aimed to
      determine the validity and reliability of a Hong Kong Chinese version of the BIQ
      to derive the DSM-5 in addition to other insomnia diagnoses in a general
      population sample. METHODS: Probability subsamples of population-based
      epidemiological survey respondents (n=2011) completed test-retest (n=120) and
      clinical reappraisal (n=176) interviews. RESULTS: Short-term test-retest
      reliability was moderate for most BIQ items (Pearson r>0.40), except for the
      number of nights with problems staying asleep, amount of time awake, duration of
      sleep problems and sleep onset latency. The areas under the receiver operating
      characteristic curve for the DSM-IV-TR, DSM-5, ICD-10 and RDC/ICSD-2 insomnia
      disorder ranged from 0.76 to 0.86, indicating high individual-level concordance
      between BIQ and clinical-interview diagnoses. The use of super-normal control and
      BIQ symptom-level data further improves the diagnostic concordance. Prevalence
      estimates based on the BIQ dichotomous classification were comparable with
      estimates based on clinical interviews for the DSM-5, RDC/ICSD-2 and any of the
      DSM-IV-TR, ICD-10 and RDC/ICSD-2 insomnia disorders. CONCLUSION: The Hong Kong
      Chinese version of the BIQ generates accurate prevalence estimates for insomnia
      disorders in the general population. Modification of the BIQ scoring algorithms
      and use of trained interviewers may further improve its diagnostic performance.

PMID- 24745777
TI  - Inflammation, sleep disturbances, and depressed mood among community-dwelling
      older men.
AB  - OBJECTIVE: High rates of sleep disturbances occur in depression. Sleep
      disturbances are linked to heightened inflammation. We sought to determine if
      sleep disturbances explain a portion of the putative inflammation - depression
      association among older adults. In late life, age-related immunoregulation
      changes may modify the inflammation-depression relationship. METHODS: Cross
      sectional associations of a panel of serum inflammatory markers with probable
      depression (measured with the Geriatric Depression Scale) were assessed among
      2560 community-dwelling older men. We tested whether inflammatory marker -
      probable depression associations were independent of chronic diseases, as well as
      objective and subjectively measured sleep disturbances. We also tested whether
      inflammation-probable depression associations were moderated by age. RESULTS:
      Inflammatory markers were not independently associated with higher odds of
      probable depression. A significant age by C-reactive protein (CRP) interaction
      (p=0.01) was detected such that the strength of the CRP-probable depression
      association decreased with age. When stratifying by the median age of 76,
      elevated odds of probable depression were found for men with CRP levels above the
      median only among the younger group (OR=2.08, 95% CI 1.18-3.69). In the final
      adjusted model, independent effects of chronic diseases and subjective sleep
      disturbances contributed to a total of 37% attenuation of the original OR
      (adjusted OR=1.68, 95% CI 0.911-3.10, p=.09). CONCLUSIONS: In late-life,
      associations between inflammatory markers and mood may be explained by both
      chronic diseases and subjectively reported sleep disturbances. Our findings
      indicate that the association of CRP with probable depression diminishes in
      strength with age.

PMID- 24745779
TI  - Burnout is associated with elevated prolactin levels in men but not in women.
AB  - OBJECTIVE: Prolactin levels have been shown to be increased by different types of
      psychosocial stress. Since burnout is a consequence of long-term psychosocial
      stress, prolactin levels might also be affected in burnout. The aim of this study
      was to investigate whether there are differences in prolactin levels between
      individuals who report burnout and others. METHOD: Morning fasting serum
      prolactin levels were compared between individuals who reported burnout (24 men
      and 25 women) and individuals who reported no burnout (25 men and 13 women).
      Women were tested in the follicular phase of the menstrual cycle. Men and women
      were analysed separately. RESULTS: Men who reported burnout exhibited
      significantly higher (34%) serum prolactin levels compared to men who reported no
      burnout. The prolactin levels in women who reported burnout were not different
      from the levels in the women who reported no burnout before or after adjusting
      for estradiol levels. CONCLUSIONS: This study indicates that prolactin levels are
      higher in men with burnout than men without burnout but not affected in women
      with burnout. Why no association was seen in women needs to be further explored.

PMID- 24745780
TI  - The relation between hostility and concurrent levels of inflammation is sex, age,
      and measure dependent.
AB  - BACKGROUND AND OBJECTIVE: Hostility may be associated with greater systemic
      inflammation. However, contradictory evidence exists. Certain individuals or
      dimensions of hostility may be more susceptible to these effects. Main and
      interactive effects of hostility with sex and/or age were evaluated on markers of
      inflammation, independently of traditional risk factors for coronary artery
      disease. METHODS: 199 healthy men (81) and women (118), aged 20-64 years (M=41 +/
      11 years) were recruited. Hostility was assessed using the Cook-Medley Hostility
      Inventory (CMHo) and ecological momentary assessments (EMA) of quarrelsome
      behavior and angry affect in daily living. Blood samples were drawn to measure
      inflammatory activity (Il-6, TNF-alpha, hsCRP, Il-8, Il-10, Il-18, MCP-1) and
      lipid oxidation (Myeloperoxidase; MPO). Correlations and hierarchical regression
      analyses were performed controlling for pertinent behavioral, psychological,
      medical, and socio-demographic factors. RESULTS: Significant univariate
      associations emerged between CMHo and Il-6, TNF-alpha, MCP-1 (p<.05).
      Hierarchical regressions showed interactions of hostility with sex (Il-6, TNF
      alpha; p<.05) and age (hsCRP, Il-6, TNF-alpha; p<.05). For example, in simple
      slope analyses, hostility was positively related to TNF-alpha in women (b=0.009,
      p=0.006) but not men. Greater hostility was also related to greater Il-6 levels
      among younger women (b=. 027, p=0.000). CONCLUSION: Hostility, particularly
      cynical hostility, may be detrimental to (younger) women. The TNF-alpha, Il-6,
      CRP triad appears vulnerable to psychological and behavioral factors, and may be
      one mechanism by which cynical hostility (CMHo) contributes to increased
      cardiovascular risk in women. Prospective research is needed to verify this.

PMID- 24745781
TI  - Early-treatment weight loss predicts 6-month weight loss in women with obesity
      and depression: implications for stepped care.
AB  - OBJECTIVE: Some adults with comorbid depression and obesity respond well to
      lifestyle interventions while others have poor outcomes. The objective of this
      study was to evaluate whether early-treatment weight loss progress predicts
      clinically significant 6-month weight loss among women with obesity and
      depression. METHODS: We conducted a secondary analysis of data from 75 women with
      obesity and depression who received a standard lifestyle intervention. Relative
      risks (RRs) and 95% confidence intervals (CIs) for achieving >=5% weight loss by
      6 months were calculated based on whether they achieved >=1 lb/week weight loss
      in weeks 2-8. Among those on target at week 3, we examined potential subsequent
      time points at which weight loss progress might identify additional individuals
      at risk for treatment failure. RESULTS: At week 2, women who averaged >=1 lb/week
      loss were twice as likely to achieve 5% weight loss by 6 months than those who
      did not (RR=2.40; 95% CI: 2.32-4.29); weight loss at weeks 3-8 was similarly
      predictive (RRs=2.02-3.20). Examining weight loss progress at week 3 and
      subsequently at a time point during weeks 4-8, 52-67% of participants were not on
      target with their weight loss, and those on target were 2-3 times as likely to
      achieve 5% weight loss by 6 months (RRs=1.82-2.92). CONCLUSION: Weight loss
      progress as early as week 2 of treatment predicts weight loss outcomes for women
      with comorbid obesity and depression, which supports the feasibility of
      developing stepped care interventions that adjust treatment intensity based on
      early progress in this population.

PMID- 24745782
TI  - Polypharmacy in multiple sclerosis: relationship with fatigue, perceived
      cognition, and objective cognitive performance.
AB  - OBJECTIVE: Patients with multiple sclerosis (MS) commonly use a variety of
      medications to slow disease progression, alleviate symptoms, and treat comorbid
      conditions. Polypharmacy has been linked to adverse outcomes in other patient
      groups, but has not been studied extensively in MS. We investigated the impact of
      polypharmacy on fatigue, objective neuropsychological performance, and subjective
      cognitive impairment in a sample of patients with MS. METHODS: MS patients (n=85)
      completed a medication inventory, self-report questionnaires, and a battery of
      neurocognitive tests. MS patients with polypharmacy were compared to MS patients
      without polypharmacy, using multivariate analysis of covariance (MANCOVA).
      RESULTS: After controlling for disease characteristics, MS patients with
      polypharmacy (n=28) exhibited prospective memory deficits and reported
      significantly more fatigue and subjective cognitive problems than MS patients
      without polypharmacy. CONCLUSION: Clinicians and patients should carefully weigh
      the costs and benefits of prescribing multiple medications, as these may
      contribute to iatrogenic fatigue and cognitive problems in MS. Moreover,
      researchers should account for polypharmacy when conducting studies examining
      fatigue and cognition in MS.

PMID- 24745783
TI  - Comparing non-specific physical symptoms in environmentally sensitive patients:
      prevalence, duration, functional status and illness behavior.
AB  - OBJECTIVE: Little is known about the potential clinical relevance of non-specific
      physical symptoms (NSPS) reported by patients with self-reported environmental
      sensitivities. This study aimed to assess NSPS in people with general
      environmental sensitivity (GES) and idiopathic environmental intolerance
      attributed to electromagnetic fields (IEI-EMF) and to determine differences in
      functional status and illness behavior. METHODS: An epidemiological study was
      conducted in the Netherlands, combining self-administered questionnaires with the
      electronic medical records of the respondents as registered by general
      practitioners. Analyses included n=5789 registered adult (>=18 years) patients,
      comprising 5073 non-sensitive (NS) individuals, 514 in the GES group and 202 in
      the IEI-EMF group. RESULTS: Participants with GES were about twice as likely to
      consult alternative therapy compared to non-sensitive individuals; those with IEI
      EMF were more than three times as likely. Moreover, there was a higher prevalence
      of symptoms and medication prescriptions and longer symptom duration among people
      with sensitivities. Increasing number and duration of self-reported NSPS were
      associated with functional impairment, illness behavior, negative symptom
      perceptions and prevalence of GP-registered NSPS in the examined groups.
      CONCLUSION: Even after adjustment for medical and psychiatric morbidity,
      environmentally sensitive individuals experience poorer health, increased illness
      behavior and more severe NSPS. The number and duration of self-reported NSPS are
      important components of symptom severity and are associated with characteristics
      similar to those of NSPS in primary care. The substantial overlap between the
      sensitive groups strengthens the notion that different types of sensitivities
      might be part of one, broader environmental illness.

PMID- 24745784
TI  - Investigating the 'placebo personality' outside the pain paradigm.
AB  - AIM: To identify personality traits related to placebo responding outside the
      context of pain. METHODS: Sixty three healthy volunteers completed the study.
      Personality traits were measured online one week prior to a laboratory session in
      which two psychosocial stress tests were administered. Prior to the second test,
      the placebo group received an intranasal spray of 'serotonin' (placebo) with the
      suggestion that it would enhance recovery. Subjective stress, heart rate and
      heart rate variability were measured. Self reported and physiological responses
      to the placebo suggestion were assessed against personality variables. RESULTS:
      Placebo effects were demonstrated in both self reported and physiological stress
      metrics. Lower optimism and less empathic concern predicted greater perceived
      benefits from the placebo treatment; and lower drive, fun, and sensation seeking
      were related to a greater physiological response to the manipulation.
      Multivariate analyses revealed lower optimism and behavioural drive to be
      predictive of responding to the placebo manipulation. CONCLUSION: Findings are in
      contrast with prior work in pain paradigms which found higher levels of the same
      traits to be related to greater placebo analgesic responses. A cluster of traits
      characterised by behavioural drive, extraversion, optimism and novelty or fun
      seeking appears to be germane to placebo responsiveness, but contextual stimuli
      may generate different patterns of responding. A new conceptualisation of placebo
      responsiveness may be useful. Rather than a 'placebo personality' it may be that
      responsiveness is better typified by a two faceted transactional model, in which
      different personality facets respond to different contextual contingencies.

PMID- 24745785
TI  - Mental disorders in leprosy: an underdiagnosed and untreated population.
AB  - OBJECTIVE: To describe the frequency of psychiatric comorbidities in leprosy
      patients and check if they had been previously diagnosed and were in psychiatric
      care. METHOD: The study was conducted with a sample of 120 leprosy patients being
      treated at two reference hospitals for leprosy in Salvador, Bahia, Brazil. Survey
      participants were more than 18 years of age, had a confirmed diagnosis of leprosy
      and was undergoing antimicrobial treatment. Patients were evaluated face-to-face
      with a socio-demographic questionnaire and the Mini-International
      Neuropsychiatric Interview (MINI-Plus) in Portuguese. The period of data
      collection was between October 2009 and June 2012. RESULTS: The assessment using
      the MINI-Plus showed that 34 (28.3%) patients did not receive any psychiatric
      diagnosis and 86 (71.7%) met the criteria for at least one. Of these 86 patients,
      25 (20.8%) had one diagnosis, 26 (21.7%) had two diagnoses and the rest, 35
      (29.2%), had three or more psychiatric diagnoses. All patients with a moderate or
      high risk of suicide had one or more psychiatric comorbidities. CONCLUSION:
      Leprosy patients have a high prevalence of psychiatric comorbidities.
      Furthermore, most of them had no previous psychiatric diagnosis and the majority
      was not undergoing treatment.

PMID- 24745786
TI  - Appropriate training based on Balint groups can improve the empathic abilities of
      medical students: a preliminary study.
AB  - OBJECTIVE: Although empathy is critical in a doctor-patient relationship,
      empathic abilities seem to decline throughout medical school. This study aimed at
      examining changes in empathic abilities of fourth-year medical students who
      participated in an optional certificate based on Balint groups. METHODS: Thirty
      four students were included in the "Balint group" certificate and compared with
      129 participating in other certificates. Before the training sessions and 4
      months later, they filled up the interpersonal reactivity index (IRI) and were
      asked to rate their emotional reactions in response to two case-reports: the
      first described a woman with diabetes, borderline- personality traits and a
      history of childhood trauma; the second, a woman with histrionic traits suffering
      from multiple sclerosis and hospitalized for functional symptoms. A principal
      component analysis extracted four factors from the 8 questions asked: empathic
      approach (e.g. finding the patient touching), rejecting-attitude, intellectual
      interest and fear of emotion contagion. RESULTS: At baseline, there were no socio
      demographic or psychological differences between groups. At follow-up, an
      increase of IRI fantasy-scale (p=0.02) and a decrease of IRI empathic-concern
      (p=0.006) were observed, regardless of the group. Empathic-approach only
      increased in the "Balint group" and for the first case-report (p=0.023), with a
      difference between the groups at follow-up (p=0.003). CONCLUSION: Results suggest
      that Balint groups may enable medical students to better handle difficult
      clinical situations such as those presented by borderline personalities. Our
      findings encourage assessing training initiatives designed at helping young
      medical students to take into account the emotional component of a doctor-patient
      relationship.

PMID- 24745787
TI  - Intentional and unintentional non-adherence to medications following an acute
      coronary syndrome: a longitudinal study.
AB  - OBJECTIVE: Non-adherence to medication is common among coronary heart disease
      patients. Non-adherence to medication may be either intentional or unintentional.
      In this analysis we provide estimates of intentional and unintentional non
      adherence in the year following an acute coronary syndrome (ACS). METHOD: In this
      descriptive prospective observational study of patients with confirmed ACS
      medication adherence measures were derived from responses to the Medication
      Adherence Report Scale at approximately 2 weeks (n=223), 6 months (n=139) and 12
      months (n=136) following discharge from acute treatment for ACS. RESULTS: Total
      medication non-adherence was 20%, 54% and 53% at each of these time points
      respectively. The corresponding figures for intentional non-adherence were 8%,
      15% and 15% and 15%, 52% and 53% for unintentional non-adherence. There were
      significant increases in the levels of medication non-adherence between the
      immediate discharge period (2 weeks) and 6 months that appeared to stabilize
      between 6 and 12 months after acute treatment for ACS. CONCLUSION: Unintentional
      non-adherence to medications may be the primary form of non-adherence in the year
      following ACS. Interventions delivered early in the post-discharge period may
      prevent the relatively high levels of non-adherence that appear to become
      established by 6 months following an ACS.

PMID- 24745788
TI  - Postencephalitic parkinsonism and selective involvement of substantia nigra in
      childhood.
AB  - Parkinsonism is a rare complication of encephalitis in childhood. Association to
      an isolated involvement of substantia nigra is exceptional. Mechanisms of nigral
      cells neurotropism remain hypothetic. We report on three children presenting with
      postencephalitic parkinsonism and selective involvement of substantia nigra, with
      literature review and we discuss pathogenic mechanisms. 

PMID- 24745789
TI  - Biologics: an update and challenge of their pharmacokinetics.
AB  - Biologics, including but not limited to monoclonal antibodies (mAbs), cytokines,
      growth factors, enzymes, hormones, vaccines, antibody fragments (e.g. Fabs), and
      antibody drug conjugates (ADCs), have a powerful clinical impact on the
      management of a wide variety of diseases. When compared to small molecules (SMs),
      they have different physicochemical properties and demonstrate unique and complex
      pharmacokinetic (PK) characteristics that are dependent on several factors such
      as net charge, neonatal Fc receptor [FcRn], Fcgamma receptor [FcgammaR],
      glycosylation, PEGylation or aggregation. While PK principles are consistent, the
      underlying mechanisms that determine processes of absorption, distribution,
      metabolism, and excretion (ADME) of biologics are quite different from those of
      SMs. Furthermore, the immunogenicity, especially formation of anti-drug antibody
      (ADA) and cellular immune responses, may play an important role in their PK.
      Investigating the drug interaction (DI) potentials of biologics is inherently
      complicated, and the most well documented DI mechanism involves cytokine-mediated
      changes in drug-metabolizing enzymes. Population PK (Pop-PK) analyses have been
      successfully applied in assessing covariates in the disposition of biologics. The
      mechanism-based (target-mediated drug disposition [TMDD]) and physiologically
      based PK (PBPK) models are applied to predict PK characteristics of biologics.
      Developing a validated bioanalytical assay (mass assay, activity assay and
      immunogenicity assay) is critical in determining the PK properties of biologics.
      In this review, we will highlight the current knowledge, as well as the
      challenges around the PK-related issues in optimization of drug development and
      clinical practice of biologics. 

PMID- 24745790
TI  - Nurse faculty perceptions of end-of-life education in the clinical setting: a
      phenomenological perspective.
AB  - BACKGROUND: Caring for patients at the end of life is an emotionally and
      physically challenging task. When patients approach the end of life, nurses are
      in a key position to enhance their quality of life by providing emotional support
      and physical symptom management. Patients and their families need nurses who are
      comfortable discussing various treatment options and levels of care. Therefore,
      it is essential that nurses receive both didactic and clinical education on end
      of-life nursing care in their nursing curriculum, before entering the healthcare
      workforce. OBJECTIVES: The purpose of this interpretive phenomenological study
      was to explore the experiences of nursing clinical instructors as they guide
      nursing students who care for dying patients in the clinical setting. DESIGN: The
      research design of this study was qualitative. SETTING: This study sought to
      explore the experiences of nursing clinical instructors; however, due to the busy
      nature of hospital nursing units, participants were interviewed in a private
      location on their university campus. PARTICIPANTS: Ten full-time nursing faculty
      members participated in this study. The average time spent in a full time faculty
      position was 16.5 years. METHODS: A semi-structured interview was conducted with
      each participant. The interviews were recorded and transcribed. Data was analyzed
      utilizing Colaizzi's method of thematic analysis. RESULTS: Six major themes
      emerged from the data, which will be discussed and illustrated with participants'
      descriptions. CONCLUSIONS: It was evident from this study that educating nursing
      students on care of a dying patient is not only important but essential to future
      nursing practice. Nurses who learn about end-of-life care from trusted nursing
      educators may enter the profession prepared to address patient's questions
      regarding end of life issues.

PMID- 24745791
TI  - Characterization of the key aroma compounds in Shiraz wine by quantitation, aroma
      reconstitution, and omission studies.
AB  - The key aroma compounds of premium Australian Shiraz wines from the warm Barossa
      Valley and cooler Margaret River regions were characterized. GC-Olfactometry was
      conducted to determine the most important volatile compounds, which were then
      quantitated. The wine from the Barossa Valley had higher concentrations of ethyl
      propanoate, dimethyl sulfide (DMS), and oak-derived compounds, whereas the
      Margaret River wine contained above threshold concentrations of the 'cheesy'
      compounds 2- and 3-methylbutanoic acid, as well as rotundone, the 'pepper'
      smelling compound. The aromas were reconstituted by combining 44 aroma compounds,
      and sensory descriptive analysis was used to investigate the importance of the
      omission of several compounds, including DMS, rotundone, fatty acids, and beta
      damascenone, and the influence of nonvolatiles was also assessed. The study
      showed that the aroma of the Shiraz wines could be reconstituted in both cases,
      with the changes in the nonvolatile fraction having a large influence. 

PMID- 24745792
TI  - Membrane structure and function: relevance of lipid and protein structures in
      cellular physiology, pathology and therapy.

PMID- 24745793
TI  - Online coupling of in-tube solid-phase microextraction with direct analysis in
      real time mass spectrometry for rapid determination of triazine herbicides in
      water using carbon-nanotubes-incorporated polymer monolith.
AB  - Online coupling of in-tube solid phase microextraction (IT-SPME) with direct
      analysis in real time mass spectrometry (DART-MS) was realized for the first time
      and applied in the analysis of triazine herbicides in lake water and orange
      juice. We incorporated single-wall carbon nanotubes (SWNTs) into a polymer
      monolith containing methacrylic acid (MAA) and ethylene dimethacrylate (EDMA) to
      form a novel poly(methacrylic acid-co-ethylene dimethacrylate-co-single wall
      carbon nanotubes) (poly(MAA-EDMA-SWNT)) monolith, which was then used in IT-SPME
      for enrichment of six triazine herbicides from water samples. With the online
      combination of IT-SPME with DART-MS, the analytes desorbed from the monolith were
      directly ionized by DART and transferred into MS for detection, thus rapid
      determination was achieved. Compared with regular DART-MS method, this online IT
      SPME-DART-MS method was more sensitive and reproducible, because of the IT-SPME
      procedures and the isotope-labeled internal standard used in the experiment. Six
      triazine herbicides were determined simultaneously using this method with good
      linearity (R(2) > 0.998). The limit of quantification (signal-to-noise ratio of
      S/N = 10) of the six herbicides were only 0.06-0.46 ng/mL. The proposed method
      has been applied to determine triazine herbicides in lake water and orange juice,
      showing satisfactory recovery (85%-106%) and reproducibility (relative standard
      deviation of RSD = 3.1%-10.9%). 

PMID- 24745794
TI  - Can surface hopping sans decoherence recover Marcus theory? Understanding the
      role of friction in a surface hopping view of electron transfer.
AB  - We compare the dynamics of Fewest Switches Surface Hopping (FSSH) in different
      parameter regimes of the spin-boson model. We show that for exceptional regions
      of the spin-boson parameter space, FSSH dynamics are in fact time-reversible. In
      these rare instances, FSSH does recover the correct Marcus rate scaling (as a
      function of diabatic coupling) without the addition of decoherence. In regions
      where dynamics are irreversible, however, FSSH does not recover the correct
      Marcus rate scaling. Finally, by comparing the friction dependence of rates
      predicted by various decoherence schemes to an analytic result by Zusman, we
      provide yet more evidence that the method of introducing decoherence has a
      qualitative effect on the accuracy of results and this effect must be treated
      carefully. 

PMID- 24745795
TI  - Urologic stenting-induced trauma: a comprehensive review and case series.
AB  - OBJECTIVE: To characterize traumatic injuries secondary to ureteral stent
      manipulation and analyze factors associated with their occurrence. METHODS: We
      performed a comprehensive retrospective review of the literature and of our
      institutional records for occurrences of iatrogenic injury because of retrograde
      ureteral stent procedures. RESULTS: Overall, 22 cases were identified, including
      3 cases at our institution. Most injuries involved a major artery (52%) or vein
      (30%), with the remainder (17%) limited to the genitourinary tract. Associated
      factors included: hydronephrosis, pelvic malignancy, indwelling or chronic
      ureteral stents, chemoradiation, and urinary diversion. CONCLUSION: Ureteral
      stenting-induced trauma is a rare but potentially life-threatening event.
      Recognition of the risk factors that predispose patients to iatrogenic stent
      trauma may help to prevent such injuries or, alternatively, it may facilitate
      their prompt diagnosis and treatment.

PMID- 24745796
TI  - Statin use and the risk of recurrence after radical prostatectomy in a cohort of
      men with inherited and/or early-onset forms of prostate cancer.
AB  - OBJECTIVE: To investigate whether the use of statin medications is associated
      with a reduced risk of biochemical recurrence (BCR) in men with inherited and/or
      early-onset prostate cancer who have been treated with radical retropubic
      prostatectomy (RRP). METHODS: Study patients are men with inherited and/or early
      onset prostate cancer enrolled in the University of Michigan Prostate Cancer
      Genetics Project. Men enrolled in Prostate Cancer Genetics Project were surveyed
      to determine statin medication use history from 1999 to 2009. Diagnosis and
      treatment data were taken from medical records. BCR was defined as a single
      increase in prostate-specific antigen level to >=0.4 ng/mL after treatment with
      RRP. Statin use was modeled as a time-dependent variable, and BCR after RRP was
      both examined using crude Cox proportional hazards models and adjusted for known
      clinical prognostic factors. RESULTS: A total of 539 men treated with RRP were
      included in this study. Of these, 47.9% of men used statin medications, and 115
      (21%) men experienced a recurrence. Ever-statin use was not associated with risk
      of recurrence in crude models (hazards ratio=1.04, 95% confidence interval=0.72
      1.49, P value=.86) or in models adjusted for clinical characteristics (hazards
      ratio=1.06, 95% confidence interval=0.68-1.64, P value=.81). Furthermore, no
      association was observed when comparing men with high-Gleason grade cancers with
      those with low-Gleason grade cancers. CONCLUSION: Statin use was not associated
      with a reduced risk of BCR after RRP in this study; however, these men at
      increased risk for prostate cancer represent a subgroup of men who may benefit
      from further study of statin medication use to slow or prevent BCR.

PMID- 24745797
TI  - Evaluation of current errors within the administration of phosphodiesterase-5
      inhibitors after more than 10 years of use.
AB  - OBJECTIVE: To detect current errors within the administration of
      phosphodiesterase type 5 inhibitors (PDE5is) and evaluate and elucidate what
      percentage of patients could be recovered for oral therapy with different
      subtypes of PDE5is through a re-education program. METHODS: Two hundred fifty
      patients remitted to the andrology unit were prospectively analyzed. Patients'
      chief complaint was erectile dysfunction despite treatment with PDE5i. The
      International Index of Erectile Function was used to measure erectile function. A
      structured interview was developed to evaluate the most frequent errors within
      the administration of PDE5is. A re-education program was offered to patients with
      incomplete or incorrect use of PDE5is according to the structured interview,
      classifying them into true nonresponders or false nonresponders. Finally, the
      percentage of patients who could be recovered for oral therapy with other PDE5is
      was analyzed. RESULTS: A total of 172 patients (69%) presented some error within
      drug administration. The most common error was not trying >1 PDE5i (41%). A re
      education program was offered to these nonresponders, and 115 (66.9%) accepted.
      Up to 27 (23.5%) did not respond to the re-education program and were classified
      as true nonresponders, whereas 88 (76.5%) had a positive response to treatment
      and were thus included in the false nonresponder group. CONCLUSION: Two-thirds of
      patients remitted to our andrology unit and cataloged as nonresponders were in
      fact using PDE5i in suboptimal conditions. Offering patients more accurate
      information provided almost 76% with good results using PDE5is and could
      therefore be successfully treated with these drugs.

PMID- 24745798
TI  - Do patients with pelvic organ prolapse have an increased frequency of
      asymptomatic microscopic hematuria?
AB  - OBJECTIVE: To determine the prevalence of asymptomatic microscopic hematuria
      (AMH) in patients with pelvic organ prolapse. METHODS: The Urogynecology patient
      database was reviewed for patients presenting between July 2010 and April 2011
      inclusive. We compared the prevalence of AMH in patients with no prolapse with
      those with prolapse. A post-hoc analysis was performed to evaluate if overall
      stage of prolapse was related to the presence of AMH. Pearson chi-square analysis
      was used for categorical variables, and P values<.05 were deemed statistically
      significant. RESULTS: Of the 230 women with evaluable AMH data, 29 (12.6%) had
      AMH. Baseline patient demographic data did not significantly differ between
      groups. Women with prolapse had a higher prevalence of AMH compared with women
      with no prolapse (18.3% vs 5.1%, P=.003). There was a significant difference in
      the distribution of AMH by stage of prolapse, with AMH more prevalent among women
      with higher stages of prolapse (P=.007). CONCLUSION: Women with prolapse beyond
      the hymen have a significantly higher prevalence of AMH when compared with women
      with prolapse at or above the hymen. We suggest an overall rate of AMH in the
      Urogynecologic population of 12.6%.

PMID- 24745799
TI  - Ventral and dorsal buccal grafting for 1-stage repair of complex anterior
      urethral strictures.
AB  - OBJECTIVE: To describe our 14-year experience with a 1-stage tissue transfer
      urethroplasty technique. METHODS: Eighteen patients underwent reconstruction with
      circumferential buccal grafting. All patients had anterior urethral strictures
      that included segments of total or near-total obliteration not amenable to
      excisional or augmented anastomotic repair and intact corpus spongiosum that
      could serve as a graft recipient bed. The mobilized corpus spongiosum was incised
      dorsally without transection, thereby preserving the continuity of the blood
      supply within the spongy tissue. Buccal mucosa was quilted to the corporal bodies
      to reconstruct the dorsal aspect of the urethra. Where there was obliterative or
      near-obliterative stricture disease, additional buccal mucosa was quilted to the
      dorsally incised, nontransected corpus spongiosum in continuity with the distally
      and proximally spatulated urethra. The repair was then completed by approximating
      dorsal and ventral buccal mucosal graft segments. RESULTS: Follow-up included
      voiding cystourethrogram at 3 weeks, cystoscopy 4 months after surgery (1 patient
      refused), and subsequent follow-up. There was 1 early stricture recurrence, which
      was successfully treated with direct vision internal urethrotomy (success 94%,
      and 100% after 1 urethrotomy). Every patient was contacted and assessed at the
      time of manuscript preparation. All patients are currently free of obstructive
      symptoms attributed to stricture disease with a mean follow-up of 50 months
      (range, 5-171 months). CONCLUSION: Dorsal and ventral buccal grafting appears to
      be an excellent option for a 1-stage repair of long obliterative anterior
      urethral strictures and strictures that include segments of obliterative or near
      obliterative disease in selected cases.

PMID- 24745800
TI  - Fetal megacystis: etiologies, management, and outcome according to the trimester.
AB  - OBJECTIVE: To describe the diagnostic criteria and outcome of fetal megacystis
      according to the gestational age at diagnosis. METHODS: A 7-year retrospective
      study was carried out from 2004 to 2011, including cases of megacystis referred
      to 2 prenatal fetal medicine units. The following data were collected and
      analyzed: maternal age, term at diagnosis (gestational weeks), ultrasonographic
      and magnetic resonance imaging data, karyotype, decision of the multidisciplinary
      prenatal team, fetopathology in cases of termination of pregnancy or fetal death,
      final diagnosis at birth after ultrasonography and voiding cystourethrography,
      and medical and surgical follow-up. RESULTS: Of the 69 fetuses included in this
      study, 82.6% were males; 26 were diagnosed during the first trimester, 21 during
      the second, and 22 during the third. During the first trimester, the main
      etiologies were urethral occlusions and prune-belly syndrome with poor fetal
      prognosis. Nineteen pregnancies (69%) were terminated for medical reasons
      including the association with other malformations, poor evolution, or
      miscarriage. Only 4 children were born alive. The main etiologies of megacystis
      discovered during the second and third trimesters were vesicoureteral reflux and
      urethral occlusion. Twenty of 22 fetuses (91%) were born alive when the fetal
      megacystis was discovered after 27 weeks of gestation. CONCLUSION: Antenatal
      discovery of megacystis is a complex and challenging prognostic situation. The
      prognosis depends on the gestational age at discovery. Megacystis is not always
      associated with obstruction. In a newborn with megacystis, bladder outlet
      obstruction has to be excluded. Optimal counseling of the involved parents
      requires a multidisciplinary approach.

PMID- 24745801
TI  - Re: Armanasco P, Williamson D, Yates B: Integration of podiatric surgery within
      an orthopaedic department: an audit of patient satisfaction with labour force
      implications. The Foot 2012;22:200-204.

PMID- 24745802
TI  - Pneumatic tourniquet use in foot and ankle surgery--is padding necessary?
AB  - BACKGROUND: The majority of foot and ankle surgery is carried out in a bloodless
      field achieved by the use of a pneumatic tourniquet. The risks of tourniquet use
      may be divided into those resulting from direct mechanical pressure from the cuff
      and those secondary to prolonged limb ischaemia. Current peri-operative
      guidelines advise the use of padding beneath the cuff, in particular to reduce
      skin complication. OBJECTIVES: To assess the complication rate of tourniquet use
      when the cuff is applied directly to the skin. METHOD: Patients undergoing foot
      and ankle surgery under tourniquet control without use of padding were assessed
      pre and post operatively for soft tissue complication, neurological deficit and
      post-tourniquet syndrome. RESULTS: We recorded findings for 97 patients, 47 thigh
      and 50 ankle tourniquets. We found a complication rate of 0%. There were no cases
      of skin blistering, abrasion, bruising, laceration or burn. CONCLUSIONS: These
      findings are contrary to published RCTs supporting the use of padding. Our study
      demonstrates the safe use of pneumatic tourniquets without padding in foot and
      ankle surgery.

PMID- 24745803
TI  - Coupling graphene mechanical resonators to superconducting microwave cavities.
AB  - Graphene is an attractive material for nanomechanical devices because it allows
      for exceptional properties, such as high frequencies, quality factors, and low
      mass. An outstanding challenge, however, has been to obtain large coupling
      between the motion and external systems for efficient readout and manipulation.
      Here, we report on a novel approach, in which we capacitively couple a high-Q
      graphene mechanical resonator (Q ~ 10(5)) to a superconducting microwave cavity.
      The initial devices exhibit a large single-photon coupling of ~10 Hz. Remarkably,
      we can electrostatically change the graphene equilibrium position and thereby
      tune the single photon coupling, the mechanical resonance frequency, and the sign
      and magnitude of the observed Duffing nonlinearity. The strong tunability opens
      up new possibilities, such as the tuning of the optomechanical coupling strength
      on a time scale faster than the inverse of the cavity line width. With realistic
      improvements, it should be possible to enter the regime of quantum optomechanics.

PMID- 24745804
TI  - Modeling biological copper clusters: synthesis of a tricopper complex, and its
      chloride- and sulfide-bridged congeners.
AB  - The synthesis and characterization of a family of tricopper clusters housed
      within a tris(beta-diketimine) cyclophane ligand (H3L) that bear structural
      similarities to biological copper clusters are reported. In all complexes, each
      Cu atom is held within the N2-chelate of a single beta-diketiminate arm. Reaction
      of L(3-) with CuCl affords an anionic complex containing a MU3-chloride donor in
      the central cavity, whereas there is no evidence for bromide incorporation in the
      product of the reaction of L(3-) with CuBr (Cu3L). Cu3L reacts with elemental
      sulfur to generate the corresponding air-stable mixed-valent (MU3
      sulfido)tricopper complex, Cu3(MU3-S)L, which represents the first example of a
      sulfide-bridged copper cluster in which each metal center is both coordinatively
      unsaturated and held within a N-rich environment. The calculated LUMO is
      predominantly Cu-S pi* in character and delocalized over all three metal centers,
      which is consistent with the isotropic ten-line absorption (g ~ 2.095, A ~ 33 G)
      observed at room temperature in EPR spectra of the one-electron chemically
      reduced complex, [Cu3(MU3-S)L](-). 

PMID- 24745805
TI  - Surgicel application in intracranial hemorrhage surgery contributed to giant-cell
      granuloma in a patient with hypertension: case report and review of the
      literature.
AB  - BACKGROUND: Surgicel is an oxidized cellulose preparation that is widely applied
      in neurosurgery due to its hemostatic effect and good tissue compatibility. Tumor
      like lesions induced by Surgicel application in cerebral surgery have been rarely
      reported, especially for intracranial hemorrhage debridement surgery in patients
      with hypertension. CASE PRESENTATION: This case report describes a rare case in
      which Surgicel application led to a foreign body reaction, contributing to the
      development of an intracranial giant-cell granuloma. A 49-year-old female
      hypertensive patient was diagnosed with intracranial hemorrhage. She was treated
      with debridement surgery that employed Surgicel application. Although a
      satisfactory hemostatic effect was achieved, the patient was diagnosed with
      epilepsy 6 months later. Subsequent magnetic resonance imaging revealed an
      intracranial space-occupying lesion. After undergoing en bloc resection of the
      lesion, the patient was diagnosed with a Surgicel-related intracranial giant-cell
      granuloma by histopathology. CONCLUSIONS: Application of Surgicel during
      intracranial hemorrhage debridement surgery may be associated with a risk of
      granuloma development due to formation of a tumor-like space-occupying lesion in
      the surgery bed. Even a low risk of tumor development implies a need for caution
      when applying Surgicel, especially when solely used to achieve a hemostatic
      effect.

PMID- 24745807
TI  - A diastereoselective one-pot, three-step cascade toward alpha-substituted
      allylboronic esters.
AB  - A new highly diastereoselective synthesis of chiral alpha-substituted
      allylboronic esters, based on a one-pot, three-step cascade, is presented. The
      palladium- and acid-cocatalyzed reaction cascade involves a desilylation of a TBS
      protected allylic alcohol, borylation, and addition of an allyl group to an
      aldehyde. Herein we present the first application of a TBS-protected allylic
      alcohol in a palladium-catalyzed borylation/allylation reaction. 

PMID- 24745809
TI  - Refractory gastroesophageal reflux disease: advances and treatment.
AB  - 'Refractory gastroesophageal reflux disease' is one of the most common misnomers
      in the area of gastroesophageal reflux disease. The term implies reflux as the
      underlying etiology despite unresponsiveness to aggressive proton pump inhibitor
      therapy. The term should be replaced with 'refractory symptoms.' We must
      acknowledge that in many patients symptoms of reflux often overlap with non-GERD
      causes such as gastroparesis, dyspepsia, hypersensitive esophagus and functional
      disorders. Lack of response to aggressive acid suppressive therapy often leads to
      diagnostic testing. In majority of patients these tests are normal. The role of
      non-acid reflux in this group is uncertain and patients should not undergo
      surgical fundoplication based on this parameter. In patients unresponsive to acid
      suppressive therapy GERD is most commonly not causal and a search for non-GERD
      causes must ensue. 

PMID- 24745810
TI  - Comparison of restrictive and liberal transfusion strategy on postoperative
      delirium in aged patients following total hip replacement: a preliminary study.
AB  - Few studies have examined the association between perioperative blood transfusion
      and postoperative delirium (POD) in aged patients undergoing total hip
      replacement surgery. In this prospective study, 186 patients older than 65 years
      undergoing elective unilateral total hip replacement surgery were enrolled. Of
      those, 94 patients were randomly assigned to the restrictive strategy transfusion
      strategy group, in which red blood cells were transfused in order to maintain
      10.0 g/dL>hemoglobin?8.0 g/dL. Ninety-two patients were randomly assigned to the
      liberal transfusion strategy group, in which red blood cells were transfused in
      order to maintain hemoglobin?10.0 g/dL. POD was diagnosed by confusion assessment
      method. The baseline characteristics of patients, the length of hospital stay,
      the incidence of POD, myocardial infarction, stroke, wound infection, pulmonary
      embolism, and the transfusion volume were recorded. No difference was observed in
      the baseline characteristics, the length of hospital stay, and the incidence of
      POD, myocardial infarction, stroke, wound infection, and pulmonary embolism
      between the two groups (P>0.05). The proportion of patients transfused with red
      blood cell and frozen plasma was decreased in the restrictive transfusion group
      compared with the liberal transfusion group (P<0.05). In conclusion, restrictive
      transfusion does not influence the incidence of POD but reduces blood
      transfusion. Thus, restrictive transfusion may serve as an effective and safe
      strategy for aged patients following total hip replacement.

PMID- 24745811
TI  - Challenges and strategies pertaining to recruitment and retention of frail
      elderly in research studies: a systematic review.
AB  - INTRODUCTION: Recruitment and retention of frail elderly in research studies can
      be difficult. OBJECTIVE: To identify challenges and strategies pertaining to
      recruitment and retention of frail elderly in research studies. METHODS: A
      systematic review was conducted. Four databases (MEDLINE, CINAHL, AgeLine,
      Embase) were searched from January 1992 to December 2012. Empirical studies were
      included if they explored barriers to or strategies for recruitment or retention
      of adults aged 60-plus who were identified as frail, vulnerable or housebound.
      Two researchers independently determined the eligibility of each abstract
      reviewed and assessed the level of evidence presented. Data concerning challenges
      encountered (type and impact) and strategies used (type and impact) were
      abstracted. RESULTS: Of 916 articles identified in the searches, 15 met the
      inclusion criteria. The level of evidence of the studies retained varied from
      poor to good. Lack of perceived benefit, distrust of research staff, poor health
      and mobility problems were identified as common challenges. The most frequently
      reported strategies used were to establish a partnership with staff that
      participants knew and trusted, and be flexible about the time and place of the
      study. However, few studies performed analyses to compare the impact of specific
      challenges and strategies on refusal or drop-out rates. CONCLUSIONS: This review
      highlights the need to improve knowledge about the impact of barriers and
      strategies on recruitment and retention of frail older adults. This knowledge
      will help to develop innovative and cost-effective ways to increase and maintain
      participation, which may improve the generalizability of research findings to
      this population.

PMID- 24745812
TI  - "Better for others than for me": a belief that should shape our efforts to
      promote participation in falls prevention strategies.
AB  - Falls are a common occurrence amongst older adults yet participation in
      prevention strategies is often poor. Although older adults may perceive a
      strategy works in general, they may not participate because they feel it will not
      benefit them personally. We aimed to describe how frequently and why older adults
      identify falls prevention strategies as being "better for others than for me". A
      cross-sectional survey with n=394 community-dwelling older adults in Victoria,
      Australia was undertaken. Participants were provided with detailed descriptions
      of four evidence-based falls prevention strategies and for each were asked
      whether they felt that the strategy would be effective in preventing falls for
      people like them, and then whether they felt that the strategy would be effective
      for preventing falls for them personally. Follow-up questions asked why they
      thought the strategy would be more effective for people like them than for them
      personally where this was the case. We found the "better for others than for me"
      perception was present for between 25% and 34% of the strategies investigated.
      Participants commonly said they felt this way because they did not think they
      were at risk of falls, and because they were doing other activities they thought
      would provide equivalent benefit. Strategies to promote participation in evidence
      based falls prevention strategies may need to convince older adults that they are
      at risk of falls and that what activities they are already doing may not provide
      adequate protection against falls in order to have greater effect. 

PMID- 24745813
TI  - Tick-borne encephalitis transmission risk: its dependence on host population
      dynamics and climate effects.
AB  - Tick-borne encephalitis (TBE) is a human disease caused by a flavivirus that is
      spread by ticks (Ixodes ricinus). In 2011 and 2012, the highest TBE incidence
      ever was recorded in Sweden. It has been proposed that warmer spring temperatures
      result in higher survival of ticks and thus high incidence of TBE. Here, analyses
      were done of time series of TBE for 1976-2011 in relation to the North Atlantic
      Oscillation (NAO), mean summer temperatures, and yearly number of harvested
      European hare (Lepus europeaus), roe deer (Capreolus capreolus), and red fox
      (Vulpes vulpes) in the County of Stockholm, the area with most TBE cases in
      recent years in Sweden. The results show that the winter NAO index or winter
      temperature has no significant effect on the variation in wildlife numbers
      harvested or TBE cases over time. Mean summer temperature above 12 degrees C had
      a slight effect, but a multivariate model revealed that only the numbers of
      European hare and red fox remained in the model and explained 64.4% of the
      variation in TBE cases. Ticks do not seem to be as sensitive to climate
      variations as anticipated, even though that summer temperature has increased by 2
      degrees C during the time period studied here. Instead, TBE cases seem to be more
      dependent on host population dynamics than on climate factors.

PMID- 24745814
TI  - Dynamics of wrist and forearm rotations.
AB  - Human movement generally involves multiple degrees of freedom (DOF) coordinated
      in a graceful and seemingly effortless manner even though the underlying dynamics
      are generally complex. Understanding these dynamics is important because it
      exposes the challenges that the neuromuscular system faces in controlling
      movement. Despite the importance of wrist and forearm rotations in everyday life,
      the dynamics of movements involving wrist and forearm rotations are currently
      unknown. Here we present equations of motion describing the torques required to
      produce movements combining flexion-extension (FE) and radial-ulnar deviation
      (RUD) of the wrist and pronation-supination (PS) of the forearm. The total torque
      is comprised of components required to overcome the effects of inertia, damping,
      stiffness, and gravity. Using experimentally measured kinematic data and subject
      specific impedance parameters (inertia, damping, and stiffness), we evaluated
      movement torques to test the following hypotheses: the dynamics of wrist and
      forearm rotations are (1) dominated by stiffness, not inertial or damping
      effects, (2) significantly coupled through interaction torques due to stiffness
      and damping (but not inertia), and (3) too complex to be well approximated by a
      simple, linear model. We found that (1) the dynamics of movements combining the
      wrist and forearm are similar to wrist rotations in that stiffness dominates over
      inertial and damping effects (p<0.0001) by approximately an order of magnitude,
      (2) the DOF of the wrist and forearm are significantly coupled through stiffness,
      while interactions due to inertia and damping are small, and (3) despite the
      complexity of the exact equations of motion, the dynamics of wrist and forearm
      rotations are well approximated by a simple, linear (but still coupled) model
      (the mean error in predicting torque was less than 1% of the maximum torque). The
      exact and approximate models are presented for modeling wrist and forearm
      rotations in future studies. 

PMID- 24745815
TI  - Influence of vertical dimension of occlusion changes on the electroencephalograms
      of complete denture wearers.
AB  - PURPOSE: The present study was conducted to identify how changes in the vertical
      dimension of occlusion (VDO) affect the sensory perception and activity of the
      brain in complete denture wearers using an electroencephalogram (EEG). METHODS:
      Subjects were 21 individuals wearing complete dentures who regularly visited the
      Division of Prosthodontics at Tsurumi University Dental Hospital for checkups (12
      males and 9 females, average age: 76.6). Based on their original dentures, two
      duplicate dentures with different VDO (-3mm and +5mm) were fabricated. EEG
      activity and occlusal force were measured before and after gum chewing with each
      denture in all subjects. Negative indicator scores for psychological conditions
      and stable neuronal activity (Dalpha) were calculated using EEG data. Statistical
      analysis was performed using the Wilcoxon test to compare changes in the sensory
      perception, activity of the brain, and occlusal force (alpha=0.05). RESULTS:
      After gum chewing with the +5-mm denture, a significant increase was observed in
      the negative indicator score (p<0.05). No significant difference was found in the
      Dalpha values before and after gum chewing with any of the dentures (p>0.05). A
      significant decrease was observed in the occlusal force between the original
      denture and the -3-mm denture (p<0.05). CONCLUSION: Psychological condition and
      occlusal force were influenced by immediate changes in the VDO of the complete
      denture.

PMID- 24745816
TI  - Phase-modulated LA-REDOR: a robust, accurate and efficient solid-state NMR
      technique for distance measurements between a spin-1/2 and a quadrupole spin.
AB  - Distances between a spin-1/2 and a spin>1/2 can be efficiently measured by a
      variety of magic-angle spinning solid state NMR methods such as Rotational Echo
      Adiabatic Passage Double Resonance (REAPDOR), Low-Alpha/Low-Amplitude REDOR (LA
      REDOR) and Rotational-Echo Saturation-Pulse Double-Resonance (R/S-RESPDOR). In
      this manuscript we show that the incorporation of a phase modulation into a long
      quadrupolar recoupling pulse, lasting 10 rotor periods that are sandwiched
      between rotor-synchronized pairs of dipolar recoupling pi pulses, extends
      significantly the range of the values of the quadrupole moments that can be
      accessed by the experiment. We show by a combination of simulations and
      experiments that the new method, phase-modulated LA-REDOR, is very weakly
      dependent on the actual value of the radio-frequency field, and is highly robust
      with respect to off-resonance irradiation. The experimental results can be fitted
      by numerical simulations or using a universal formula corresponding to an equal
      transition-probability model. Phase-modulated LA-REDOR (13)C{(11)B} and
      (15)N{(51)V} dipolar recoupling experiments confirm the accuracy and
      applicability of this new method. 

PMID- 24745817
TI  - Glycaemic control: a balancing act or a different approach?
AB  - The prevalence of diabetes is increasing world-wide. Tight glycaemic control has
      been shown to reduce diabetes complications in a number of landmark trials. Apart
      from increasing the risk of microvascular and macrovascular disease, poor
      glycaemic control is also associated with cognitive and memory impairment as well
      as with mood disturbance. However, tighter glycaemic control with conventional
      anti-hyperglycaemic medication is also associated with increased risk of
      hypoglycaemia. There is increasing evidence that hypoglycaemia is much more than
      a troublesome inconvenience. Indeed it is associated with acute cognitive
      impairment, dementia, increased risk of falls, rebound hyperglycaemia with
      consequent loss of glycaemic control, acute coronary syndrome and increased
      mortality. Hence, a very difficult balance needs to be achieved so as to achieve
      the best glycaemic control possible, whilst avoiding hypoglycaemia. This paper
      will briefly discuss the potential benefits of tight glycemic control and reviews
      the risks associated with hypoglycaemia. A paradigm shift in diabetes care may be
      needed; use of newer anti-hyperglycemic agents with low hypoglycaemia risk may
      allow us to achieve good control in most patients whilst avoiding the serious
      consequences of hypoglycaemia. This may be especially important in those at
      significant risk of hypoglycaemia (e.g. those with brittle diabetes) or of its
      consequences such as elderly patients, those in certain occupations or those with
      cardiovascular disease or epilepsy. 

PMID- 24745819
TI  - Direct detection and identification of acid-fast bacteria from smear-positive
      broth cultures using a pyrosequencing method.
AB  - Broth culture is a standard method for detection of acid-fast bacteria (AFB)
      (e.g., Mycobacterium and Nocardia) from patient specimens. Direct nucleic acid
      based identification from smear-positive broths expedites the infectious disease
      diagnosis. We developed and evaluated the performance of a pyrogram-based
      technique (direct-broth-pyrosequencing [DBP]) to identify AFB directly from smear
      positive broths. One hundred thirteen AFB-positive broths from patient specimens
      were tested. Bacterial DNA was amplified by polymerase chain reaction and
      sequenced using the PyroMark ID system. The DBP method correctly identified the
      AFB species/group in 109 (97%) of the 113 broths, including 15 Mycobacterium
      species and 4 Nocardia species. Three broths that yielded indeterminate results
      were found to be AFB-AFB mixed broths and required purified colonies on solid
      media for definite identification. The 4th broth was repeatedly identified by
      sequencing to be Mycobacterium intracellulare, even though the organism was not
      isolated and the AccuProbe was negative. This method did not identify the AFB
      organisms from broths containing 2 AFB organisms, but did not produce false
      identification. No cross-reaction was observed when AFB-positive broths were
      spiked with non-AFB microorganisms, indicating that the DBP method was specific
      to AFB. The DBP method gives rapid (within 8 h), accurate AFB identification
      directly from broth cultures and provides another useful AFB identification tool
      in a clinical laboratory. 

PMID- 24745820
TI  - Superantigen profiling of Staphylococcus aureus infective endocarditis isolates.
AB  - The frequency of superantigen production among Staphylococcus aureus isolates
      associated with endocarditis is not well defined. We tested 154 S. aureus
      isolates from definite infective endocarditis cases for the presence of
      staphylococcal enterotoxins A-E, H, and TSST-1 by PCR, enzyme-linked
      immunosorbent assay, and using an HLA-DR3 transgenic mouse splenocyte
      proliferation assay. Sixty-three isolates (50.8%) tested positive for at least 1
      superantigen gene, with 21 (16.9%) testing positive for more than 2. tst (28.6%)
      was most common, followed by seb (27%), sea (22.2%), sed (20.6%), see (17.5%),
      and sec (11.1%). Of 41 methicillin-resistant S. aureus, 21 had superantigen
      genes, with sed being more frequently detected in this group compared to
      methicillin-susceptible S. aureus (P < 0.05). Superantigen genes were not
      associated with mortality (P = 0.81). 75% of PCR-positive isolates induced robust
      splenocyte proliferation. Overall, more than half of S. aureus isolates causing
      endocarditis carry superantigen genes, of which most are functional. 

PMID- 24745821
TI  - Beneficial effects of selective vitamin D receptor activation by paricalcitol in
      chronic kidney disease.
AB  - In chronic kidney disease patients, active vitamin D level progressively declines
      in the course of the disease. This phenomenon is accompanied by elevation of
      parathyroid hormone, resulting in secondary hyperparathyroidism (SHPT), increased
      phosphorus levels, and hypocalcemia. All these disorders are associated with high
      rates of cardiovascular morbidity and mortality in these patients. Many vitamin D
      analogs have been approved for the treatment of SHPT in renal patients.
      Currently, new and more selective vitamin D receptor activators (VDRAs) have been
      introduced in this therapy with the aim of reducing SHPT without the
      hypercalcemia and hyperphosphatemia associated with the use of nonselective
      VDRAs. In addition, amelioration in hypertension, albuminuria, insulin
      resistance, and inflammation have been suggested as consequences of vitamin D
      receptor (VDR) activation. In this work, we summarize the beneficial effects
      attributed to paricalcitol, the only selective, new generation VDRA, currently
      available in Europe and the USA, with proven efficacy in the control of SHPT both
      in hemodialysis (HD) and pre-dialysis patients. Paricalcitol exerts less calcemic
      and phosphatemic effects than other VDRAs and prevents deleterious bone
      resorption. Moreover, paricalcitol-based therapy has been related to beneficial
      effects that could favor survival rates in chronic kidney disease patients. These
      benefits include anti-inflammatory and antithrombotic effects, the inhibition of
      vascular smooth muscle cell proliferation, the reninangiotensin system, vascular
      calcification, and regression of left ventricular hypertrophy, which could reduce
      the risk of cardiovascular mortality. 

PMID- 24745822
TI  - Mitochondrial pathology in osteoarthritic chondrocytes.
AB  - Osteoarthritis (OA) is a chronic degenerative disease leading to aberrance of
      cartilage structures with unclear or multifactorial mechanisms. Recently, a great
      portion of research endeavor to explore the molecular mechanisms of OA in
      focusing on the mitochondrial pathology. Mitochondrial respiratory chain (MRC)
      produces reactive oxygen species (ROS), which in turn impair mtDNA integrity and
      link to cartilage degradation in OA. The fine-tuning between ROS and antioxidant
      within chondrocytes ensures cartilage homeostasis. With disturbance from pro
      inflammatory cytokines, oxidative stress synergistically instigates cellular
      signaling and exacerbates mitochondrial pathology, which may affect several
      pathways implicated in OA cartilage degradation, including oxidative stress,
      increase of cytokine-induced chondrocytes inflammation and matrix catabolism,
      aging and senescence, obesity-related pathology, and cartilage matrix
      calcification. Unveiling the molecular mechanisms of mitochondrial function in OA
      pathogenesis and progression is essential for providing relevant therapeutic
      targets. These suggest that efficient protection and improvement of mitochondrial
      activity can be a therapeutic alternative for OA patients. 

PMID- 24745823
TI  - Diagnosis of peripheral pulmonary lesions with radial probe endobronchial
      ultrasound-guided bronchoscopy.
AB  - INTRODUCTION: The diagnosis of peripheral pulmonary lesions (PPLs) is a
      challenging task for pulmonologists. Radial probe endobronchial ultrasound (R
      EBUS) has been developed to enhance diagnostic yield. The objective of this study
      was to evaluate the effectiveness of R-EBUS in the diagnosis of PPLs. METHODS: A
      retrospective study was conducted on 174 patients diagnosed with PPLs who
      underwent EBUS-guided bronchoscopy. Histological examination of specimens
      obtained by transbronchial lung biopsy (TBLB) and cytological examinations of
      brushing smear, brush rinse fluid and bronchoalveolar lavage fluid (BALF) were
      evaluated for the diagnosis. RESULTS: The mean diameter of the PPLs was 25.1 +/-
      10.7 mm. The final diagnoses included 129 malignancies and 45 benign lesions. The
      overall diagnostic yield of EBUS-guided bronchoscopy was 79.9%. Neither size nor
      etiology of the PPLs influenced the diagnostic performance of EBUS-guided
      bronchoscopy (82.9% vs. 74.6% for PPLs>20mm and PPLs<=20mm; p=0.19, and 82.9% vs.
      71.1% for malignancy and benign diseases; p=0.09). TBLB rendered the highest
      yield among these specimens (69.0%, 50.6%, 42.0%, and 44.3% for TBLB, brushing
      smear, brush rinse fluid, and BALF, respectively; p<0.001). The combination of
      TBLB, brush smear, and BALF provided the greatest diagnostic yield, while brush
      rinse fluid did not add benefits to the outcomes. CONCLUSION: R-EBUS-guided
      bronchoscopy is a useful technique in the diagnosis of PPLs. To achieve the
      highest diagnostic performance, TBLB, brushing smear and bronchoalveolar lavage
      should be performed together.

PMID- 24745825
TI  - Clinical significance of elevated serum soluble CD40 ligand levels as a
      diagnostic and prognostic tumor marker for pancreatic ductal adenocarcinoma.
AB  - BACKGROUND: CD40-CD40 ligand (CD40L) interaction is considered to contribute to
      the promotion of prothrombotic responses and production of angiogenesis
      associated factor in addition to adaptive immune responses. Recently, the role of
      soluble CD40L (sCD40L) has gained interest in cancer, although its exact
      functions remain unknown. This study evaluated the clinical significance of
      sCD40L in patients with pancreatic ductal adenocarcinoma (PDAC) and validated its
      utility as a PDAC diagnostic and prognostic biomarker. METHODS: Serum sCD40L
      levels were measured by chemiluminescent immunoassay and compared among normal,
      chronic pancreatitis (CP, high-risk), and PDAC group in both training (n=25 per
      group) and independent validation (n=30, 30, and 55, respectively) datasets
      through one-way ANOVA test with the post-hoc Bonferroni method. To evaluate the
      diagnostic potential of serum sCD40L for PDAC, receiver operating characteristic
      (ROC) curves were generated and logistic regression analysis was conducted. To
      investigate the sCD40L-assoicated cytokines/chemokines in PDAC,
      cytokines/chemokines levels were analyzed by a MILLIPLEX MAP Human
      Cytokine/Chemokine Kit. To assess the prognostic potentials of sCD40L, Kaplan
      Meier survival curve and Cox proportional-hazards regression analysis were
      applied. RESULTS: Serum sCD40L levels were significantly higher in PDAC group
      compared with non-cancer groups in both training (p<0.05) and validation (p<0.05)
      datasets. Clinically, serum sCD40L closely correlated with unresectability
      (gammas=0.342, p=0.011) and distant metastasis (gammas=0.294, p=0.030) of PDAC.
      ROC curve and logistic regression analysis demonstrated the remarkable predictive
      potentials of serum sCD40L for PDAC (80.0% sensitivity and 85.5% specificity at
      cut-off point, 0.45; logistic regression), superior to those of CA19-9 and CEA.
      According to cytokines/chemokines assay, serum sCD40L levels were closely
      correlated with serum levels of pro-angiogenic cytokines (EGF, VEGF, IL-8) and
      immunosuppressive cytokines (IL-6, IL-10, IL-1RA). Kaplan-Meier survival analysis
      demonstrated patients with high-serum sCD40L (>35,000 ng/ml) had a poorer
      prognosis than those with low-serum sCD40L (log-rank, p=0.015). Multivariate Cox
      regression analysis yielded a hazard ratio of 2.509 (95% CI, 1.038-6.067,
      p=0.041) for mortality in the high-serum sCD40L group. CONCLUSIONS: Serum sCD40L
      is correlated with immunosuppression and angiogenesis in PDAC
      carcinogenesis/progression, and is a promising diagnostic and prognostic
      biomarker for PDAC superior to CA19-9 and CEA.

PMID- 24745826
TI  - Synthesis, structure, and magnetic properties of (Tb(1-x)Mn(y))MnO(3-delta).
AB  - Two compounds (Tb(1-x)Mn(y))MnO(3-delta) (W1, x = 0.089, y = 0.063; W2, x =
      0.122, y = 0.102) have been synthesized by solid-state method and characterized
      using neutron diffraction and magnetic measurements. They crystallize in space
      group Pnma at room temperature and Pna21 at low temperature. W1 shows a
      sinusoidal antiferromagnetic order, and W2 shows both sinusoidal and canted
      commensurate antiferromagnetic orders. The magnetic moments of the commensurate
      antiferromagnetic order for W2 are antiferromagnetically coupled along the a- and
      c-axes, and ferromagnetically coupled along the b-axis in the Pna21 setting.
      Strong ferromagnetic response is induced by doping more Mn into the Tb site of
      (Tb(1-x)Mn(y))MnO(3-delta).

PMID- 24745827
TI  - Characterization and quantitation of anthocyanins and other phenolics in native
      Andean potatoes.
AB  - Andean potatoes are gaining popularity not only for their appealing colors and
      culinary uses but also for their potential higher content of polyphenolic
      compounds. The objective of this study was to identify potato varieties with
      increased phenolic content. This was achieved through characterization and
      quantitation of the phenolic composition in 20 varieties of native Andean
      potatoes from 4 different Solanum species with different colors. Major
      quantitative and qualitative differences among evaluated samples were more
      dependent on the coloration of the extracted sample rather than on the species.
      The most predominant anthocyanidins were petunidin-3-coumaroylrutinoside-5
      glucoside and pelargonidin-3-coumaroylrutinoside-5-glucoside in purple and red
      potato extracts, respectively, while chlorogenic acid and its isomers were the
      main phenolic compund (43% of the total phenolic content). Our study suggested
      that the appropriate selection of native potatoes could provide new sources of
      polyphenolics with health promoting properties and natural pigments with
      increased stability for food applications. 

PMID- 24745828
TI  - Unintentional high-density p-type modulation doping of a GaAs/AlAs core
      multishell nanowire.
AB  - Achieving significant doping in GaAs/AlAs core/shell nanowires (NWs) is of
      considerable technological importance but remains a challenge due to the
      amphoteric behavior of the dopant atoms. Here we show that placing a narrow GaAs
      quantum well in the AlAs shell effectively getters residual carbon acceptors
      leading to an unintentional p-type doping. Magneto-optical studies of such a
      GaAs/AlAs core-multishell NW reveal quantum confined emission. Theoretical
      calculations of NW electronic structure confirm quantum confinement of carriers
      at the core/shell interface due to the presence of ionized carbon acceptors in
      the 1 nm GaAs layer in the shell. Microphotoluminescence in high magnetic field
      shows a clear signature of avoided crossings of the n = 0 Landau level emission
      line with the n = 2 Landau level TO phonon replica. The coupling is caused by the
      resonant hole-phonon interaction, which points to a large two-dimensional hole
      density in the structure. 

PMID- 24745829
TI  - Telling adolescents a parent is dying.
AB  - BACKGROUND: When a parent is terminally ill, one of the major challenges facing
      families is informing children of the parent's condition and prognosis. This
      study describes four ways in which parents disclose information about a parent's
      life-threatening illness to their adolescent children. METHODS: We audio-recorded
      and transcribed 61 individual interviews with hospice patients who were recruited
      from a large hospice in northeastern Ohio, their spouses/partners, and their
      adolescent children. The interviews were coded and analyzed using a constant
      comparison approach. RESULTS AND CONCLUSIONS: Families inform adolescents about
      the progression of a parent's terminal illness in characteristic ways that remain
      fairly consistent throughout the illness, and are aimed at easing the
      adolescents' burden and distress. The families engaged in the process of
      disclosure in one of four ways: measured telling, skirted telling, matter-of-fact
      telling, and inconsistent telling. These results will inform the development of
      interventions that assist families with disclosure and are tailored to each
      family's communication style.

PMID- 24745830
TI  - Mutations in HOXA11 are not responsible for Mullerian duct anomalies in Chinese
      patients.
AB  - As a member of the homeobox (HOX) gene family, HOXA11 is expressed in the
      primordia of lower uterus and cervix during fetal life and is essential for
      endometrial development and embryo implantation in the adults. The aim of the
      present study was to investigate whether mutations in HOXA11 contribute to
      Mullerian duct anomalies (MDA) in Chinese. A cohort of 192 patients with MDA and
      192 healthy controls was enrolled. Genomic DNA was extracted. All exons and exon
      intron boundaries were amplified and sequenced. One novel synonymous variant
      (c.774G>A) and one known single-nucleotide polymorphism were identified, both of
      which were not found in the matched controls. The results suggest that mutations
      in the coding region of HOXA11 are not common in Chinese women with MDA. As a
      member of the homeobox gene family, HOXA11 is expressed in the primordia of lower
      uterus and cervix during fetal life and is essential for endometrial development
      and embryo implantation in the adults. The aim of the present study was to
      investigate whether mutations in HOXA11 contribute to Mullerian duct anomalies
      (MDA) in Chinese. A cohort of 192 patients with MDA and 192 healthy controls was
      enrolled. Genomic DNA was extracted. All exons and exon-intron boundaries were
      amplified and sequenced. One novel synonymous variant (c.774G>A) and one known
      single-nucleotide polymorphism were identified, both of which were not found in
      the matched controls. The results suggest that mutations in the coding region of
      HOXA11 are not common in Chinese women with MDA. 

PMID- 24745831
TI  - Adenomyosis and reproductive performance after surgery for rectovaginal and
      colorectal endometriosis: a systematic review and meta-analysis.
AB  - The relationship between rectovaginal-bowel endometriosis and fertility is
      unclear. Nevertheless, extirpative surgery, including colorectal resection, is
      being fostered as a fertility-enhancing procedure. Adenomyosis and deep
      endometriosis often coexist. As the uterine condition may further impact on
      reproductive outcome, this work performed a systematic literature review with the
      objective of identifying all English-language reports on surgical treatment for
      rectovaginal and colorectal endometriosis, including bowel resection, in which
      participants were screened preoperatively for uterine adenomyosis. Risk ratios
      (RR) were then combined in a meta-analysis. In the five selected observational
      studies, in women seeking pregnancy, 7/59 (11.9%) with concomitant adenomyosis
      conceived, compared with 74/172 (43.0%) in those without adenomyosis. Adenomyosis
      was never excised. One in 10 women experienced a major surgical complication. The
      RR of clinical pregnancy ranged from 0.23 to 0.46, with absence of heterogeneity
      among studies (I(2)=0.0%). Pooling of the results yielded a common RR of 0.32
      (95% confidence interval 0.16 to 0.66). No small-study effect was detected
      (Egger's test). Screening for adenomyosis before suggesting difficult and risky
      procedures may allow identification of a subgroup of patients at particularly
      worse prognosis for which surgery would have a marginal effect on the likelihood
      of conception. Deep endometriosis may infiltrate the rectum, vagina and sigmoid
      colon. These severe forms are usually associated with pain, but their
      relationship with fertility is unclear. Despite lack of convincing evidence,
      extirpative surgery, including colorectal resection, is being fostered as a
      fertility-enhancing procedure, although these procedures may cause major
      complications. Adenomyosis (i.e. the infiltration of the uterine wall by
      endometrial glands) often coexists with deep endometriosis, and several
      investigators believe that the former condition may have a detrimental effect on
      fertility more than the latter. If this is true, screening for adenomyosis may
      allow preoperative identification of a subgroup of patients at particularly worse
      prognosis for whom difficult and risky surgery would have a marginal or no effect
      on the likelihood of conception. To disentangle this issue, we performed a
      systematic literature review with the objective of identifying all English
      language reports on surgical treatment for rectovaginal and colorectal
      endometriosis, including bowel resection, in which participants were also
      investigated preoperatively for uterine adenomyosis. Risk ratios (RR) were then
      combined in a meta-analysis. In the five selected observational studies, in women
      seeking pregnancy, 7/59 (11.9%) women with concomitant adenomyosis conceived,
      compared with 74/172 (43.0%) in those without adenomyosis. One in 10 women
      experienced a major surgical complication. The RR of clinical pregnancy
      consistently ranged from 0.23 to 0.46. Pooling of the results yielded a common RR
      of 0.32 (95% CI 0.16-0.66). Adenomyosis was associated with a 68% reduction in
      the likelihood of pregnancy in women seeking conception after surgery for
      rectovaginal and colorectal endometriosis. 

PMID- 24745832
TI  - Novel aspects of the endocrinology of the menstrual cycle.
AB  - Ovarian control of gonadotrophin secretion is normally achieved via the feedback
      mechanisms mediated by oestradiol and progesterone. Evidence has been provided
      that nonsteroidal substances, such as inhibin A and B, participate in the
      negative feedback control of FSH secretion. Another nonsteroidal ovarian
      substance is gonadotrophin surge-attenuating factor (GnSAF), the activity of
      which is particularly evident in women undergoing ovulation induction.
      Accumulating evidence has suggested that GnSAF plays a physiological role during
      the menstrual cycle. In particular, this factor antagonizes the sensitizing
      effect of oestradiol on the pituitary response to gonadotrophin-releasing hormone
      during the follicular phase of the cycle. A hypothesis has been developed that,
      in the late follicular phase, the activity of GnSAF is reduced and this
      facilitates the sensitizing effect of oestradiol on the pituitary, thus enforcing
      the massive discharge of gonadotrophins at the midcycle LH surge. The interaction
      of oestradiol, progesterone and GnSAF on the hypothalamic-pituitary system
      provides a novel approach to explain the mechanisms which control LH secretion
      during the normal menstrual cycle. The ovarian control of gonadotrophin secretion
      during the normal menstrual cycle is achieved via negative and positive feedback
      mechanisms. The steroids oestradiol and progesterone are the main regulators;
      however, nonsteroidal substances, such as inhibin A and inhibn B, also
      participate. Accumulating evidence has demonstrated that another nonsteroidal
      ovarian substance, gonadotrophin surge-attenuating factor (GnSAF), plays a key
      role in the control of LH secretion during the follicular phase and at midcycle,
      providing thus a novel aspect in the ovarian control of gonadotrophin secretion
      during the human menstrual cycle. The ovarian control of gonadotrophin secretion
      during the normal menstrual cycle is achieved via negative and positive feedback
      mechanisms. The steroids oestradiol and progesterone are the main regulators;
      however, nonsteroidal substances, such as inhibin A and inhibn B, also
      participate. Accumulating evidence has demonstrated that another nonsteroidal
      ovarian substance, gonadotrophin surge-attenuating factor (GnSAF), plays a key
      role in the control of LH secretion during the follicular phase and at midcycle,
      providing thus a novel aspect in the ovarian control of gonadotrophin secretion
      during the human menstrual cycle.

PMID- 24745833
TI  - Endometrial nerve fibre density in patients undergoing IVF: a pilot study.
AB  - The presence of nerve fibres in the functional layer of the endometrium has been
      strongly associated with endometriosis. Presence of nerve fibres in the
      endometrium of women undergoing IVF has not been previously assessed. This
      prospective pilot study assessed the presence of nerve fibres in endometrium of
      women undergoing IVF due to various causes and examined the correlation between
      the presence of nerve fibres and IVF success. A total of 32 IVF patients
      underwent endometrial biopsy during days 21-23 of the menstrual cycle. Nerve
      fibres were identified by immunohistochemical staining. Correlations between the
      presence and density of nerve fibres and aetiology of infertility and IVF success
      were measured. Nerve fibres were identified in the endometrium of 10/31 (32.3%)
      women with a satisfactory biopsy. Presence of nerve fibres was not correlated
      with cause of infertility. Clinical pregnancy was achieved in 12/32 (37.5%)
      patients, without correlation to presence of nerve fibres in the endometrium.
      Nerve fibres were identified in a substantial percentage of women undergoing IVF,
      possibly reflecting underdiagnosis of endometriosis in this population. The
      presence of nerve fibres does not appear to interfere with implantation. The
      significance of nerve fibres in the endometrium of IVF patients warrants further
      research. The presence of nerve fibres in the functional layer of the endometrium
      has been strongly associated with endometriosis. The presence of nerve fibres in
      the endometrium of women undergoing IVF has not been previously assessed. Our aim
      was to assess the presence of nerve fibres in endometrium of women with various
      causes of infertility undergoing IVF and to examine the association between the
      presence of nerve fibres in the endometrium and IVF success. In a prospective
      study, 32 IVF patients underwent endometrial biopsy during days 21-23 of the
      menstrual cycle. Nerve fibres were identified by immunohistochemical staining.
      Associations between the presence and density of nerve fibres and the aetiology
      of infertility and IVF success were measured. Nerve fibres were identified in the
      endometrium of 10/31 (32.3%) women with a satisfactory biopsy. No association was
      found between the presence of nerve fibres and the cause of infertility. Clinical
      pregnancy was achieved in 12/32 (37.5%) patients, without association with the
      presence of nerve fibres in the endometrium. Nerve fibres can be identified in a
      substantial percentage of women undergoing IVF, possibly reflecting
      underdiagnosis of endometriosis in this population. Their presence does not
      interfere with embryo implantation. The significance of nerve fibres in the
      endometrium of IVF patients warrants further research. 

PMID- 24745834
TI  - Role of dehydroepiandrosterone in improving oocyte and embryo quality in IVF
      cycles.
AB  - The purpose of this study was to evaluate the role of dehydroepiandrosterone
      (DHEA) on the number and quality of oocytes and embryos in poor responders
      undergoing IVF cycles. A total of 50 patients with a history of poor ovarian
      response in the previous cycle(s) were enrolled in a prospective cohort study.
      They were treated with oral micronized DHEA 25mg three times a day for 4 months.
      Oocyte and embryo number and quality were recorded before and after treatment.
      The results were analysed using Student's paired t-test. After treatment with
      DHEA, a significant increase in number of mature follicles was seen in the post
      treatment period (? 35 years P<0.001; ? 36 years P = 0.002). There were
      significant increases in numbers of oocytes retrieved, fertilization rates and,
      consequently, the total number of embryos available. More embryos were vitrified
      among patients ? 35 years (P<0.001) post treatment, and clinical pregnancy rate
      in this group was 26.7%. DHEA treatment resulted in a higher number of oocytes
      retrieved, oocytes fertilized, embryos overall and of grade-I embryos. It can
      help in increasing pregnancy rate in poor responders. This study was performed to
      evaluate the role of dehydroepiandrosterone (DHEA) treatment on the number and
      quality of oocytes and embryos in poor responders undergoing IVF cycles. Fifty
      patients with a history of poor ovarian response in the previous cycle(s) were
      enrolled in the study and a prospective cohort study was performed. Patients were
      prescribed oral micronized DHEA 25mg three times a day for 4 months. Oocytes and
      embryos in terms of both number and quality were measured before and after
      treatment. A significant increase in mean number of mature follicles was seen in
      the post-treatment group. There was a significant increase in the number of
      oocytes retrieved, fertilization rates and, consequently, in the total number of
      embryos available after treatment with DHEA. More embryos were vitrified post
      treatment and the overall pregnancy rate was 20%. DHEA resulted in a significant
      improvement in the numbers of oocytes retrieved, oocytes fertilized, embryos and
      grade-I embryos. DHEA can help improve pregnancy rate in poor responders with
      history of previous failed IVF cycles.

PMID- 24745835
TI  - Live birth using vitrified--warmed oocytes in invasive ovarian cancer: case
      report and literature review.
AB  - This article reports the live birth of a healthy newborn using vitrified-warmed
      oocytes in a young patient with invasive mucinous ovarian carcinoma (stage Ic).
      Diagnosis was performed after a laparoscopic left adnexectomy. She underwent two
      cycles of ovarian stimulation, and 14 oocytes were vitrified before fertility
      sparing surgery with uterus preservation went ahead. One year later, a transfer
      of two embryos was performed after insemination of warmed oocytes. Eighteen days
      after the transfer, she underwent a laparotomy because of abdominal pain, vaginal
      bleeding and haemoperitoneum. A right cornual ectopic pregnancy in the uterus was
      diagnosed and a wedge resection was performed to resolve it. One week later, a
      viable intrauterine pregnancy was confirmed under ultrasound. An elective
      Caesarean section was performed at week 38 of gestation, resulting in the birth
      of a healthy boy weighing 2650 g. As far as is known, this is the first live
      birth reported through vitrified-warmed oocytes in a patient with invasive
      ovarian cancer. Although oocyte vitrification is an alternative to be considered
      for fertility preservation in highly selected cases of ovarian cancer,
      controversial issues are discussed. Fertility preservation is a proven
      possibility in some cancer patients according to their age, disease and time
      available until the beginning of their oncological treatment. Although oocyte
      vitrification is an alternative to be considered for fertility preservation in
      highly selected cases of ovarian cancer, no live birth has been reported. We
      report the live birth of a healthy newborn through vitrified-warmed oocytes in a
      young patient with invasive mucinous ovarian carcinoma (stage Ic). Diagnosis was
      performed after a laparoscopic left adnexectomy. She underwent two cycles of
      ovarian stimulation, and 14 oocytes were vitrified before fertility-sparing
      surgery with uterus preservation went ahead. One year later, a transfer of two
      embryos was performed after the insemination of the warmed oocytes. Eighteen days
      after the transfer she underwent a laparotomy because of abdominal pain, vaginal
      bleeding and haemoperitoneum. A right cornual ectopic pregnancy in the uterus was
      diagnosed and a wedge resection was performed to resolve it. One week later, a
      viable intrauterine pregnancy was confirmed under ultrasound. An elective
      Caesarean section was performed at week 38 of gestation, resulting in the birth
      of a healthy boy weighing 2650 g. To our knowledge, this is the first live birth
      reported using vitrified-warmed oocytes in invasive ovarian cancer. Controversial
      issues are reviewed and discussed.

PMID- 24745836
TI  - Cell lines from morphologically abnormal discarded IVF embryos are typically
      euploid and unaccompanied by intrachromosomal aberrations.
AB  - Routine IVF practices result in the discarding of a significant proportion of
      embryos due to their unsuitability for transfer or cryopreservation. The present
      study plated clinically unusable human blastocysts to derive cellular outgrowths
      for aneuploidy studies and genome-wide analysis of DNA copy number variations,
      and to evaluate their potential as a source for pluripotent stem cells. Just 79
      cellular outgrowths were obtained from 1026 abnormal blastocysts (7.7%),
      reflecting their low developmental potential. Of these, 13 (16.5%) were
      karyotypically abnormal and included trisomies frequently detected in
      miscarriages, each of which was uniform (nonmosaic) and the result of meiotic
      nondisjunction. Evaluation of submicroscopic DNA gains and losses in 10 diploid
      cellular outgrowths did not identify increased rates of copy number variations.
      Five of these outgrowths were shown to express pluripotency markers and could be
      developed into cell lineages representative of the three germ layers. These data
      suggest that embryos with chromosomal abnormalities resist cell-line derivation,
      and mosaic aneuploidy produced from mitotic nondisjunction, common in
      preimplantation embryos, is likely to be diminished or lost under conditions of
      diploid cell competition. Furthermore, this work demonstrated that abnormal
      embryos discarded in IVF programmes can provide a valuable source for pluripotent
      stem cell lines. During IVF, a large proportion of embryos are clinically
      unsuitable due to abnormal development and these embryos only have a small chance
      of achieving a pregnancy. Here we used these abnormal embryos to create cell
      lines for genetic testing and to determine their potential as stem cells. Of the
      1026 abnormal embryos used, 79 (7.7%) created cell lines, reflecting their low
      developmental potential. Of those, only 16.5% had chromosomal anomalies, a much
      lower number than expected. This included chromosome abnormalities frequently
      observed in miscarriages, all of which were found in each cell tested (nonmosaic)
      and originated from the egg or the sperm as opposed to cell division. In-depth
      testing of 10 normal cell lines for small DNA gains and losses did not reveal an
      increased frequency of mutations. Furthermore, five of the cell lines were
      examined for stem cell properties and found to exhibit the hallmark features of
      stem cells including their ability to make mature cells from different parts of
      the body. Our data suggest that embryos with abnormal chromosomes resist making
      cell lines and that abnormalities that arise during cell division are likely to
      be lost due to competition with normal cells. We also demonstrated that abnormal
      embryos usually discarded in IVF programmes can provide a valuable source for
      stem cell lines. 

PMID- 24745837
TI  - Folic acid supplementation and IVF pregnancy outcome in women with unexplained
      infertility.
AB  - Folic acid supplements are commonly used by infertile women which leads to a
      positive folate status. However, the effect of folic acid supplements on
      pregnancy outcome in women with unexplained infertility has not been well
      investigated. This study evaluated folic acid supplement use and folate status in
      women with unexplained infertility in relation to IVF pregnancy outcome. In
      addition, use of folic acid supplements and folate status were compared between
      women with unexplained infertility and fertile, nonpregnant control women. Women
      with unexplained infertility used significantly more folic acid supplements and
      had higher median total folic acid intake from supplements compared with fertile
      control women (both P < 0.001). Women with unexplained infertility also had
      significantly higher median plasma folate and lower median plasma homocysteine
      concentrations than fertile women (both P < 0.001), but folic acid
      supplementation or folate status were not related to pregnancy outcome in women
      with unexplained infertility. In conclusion, folic acid supplementation or good
      folate status did not have a positive effect on pregnancy outcome following
      infertility treatment in women with unexplained infertility. Folate is one of the
      B vitamins which has been suggested to be related to infertility. Folic acid is
      an artificial form of folate which is commonly used in dietary supplements. Folic
      acid supplementation has been shown to increase folate concentrations and
      decrease concentrations of the amino acid homocysteine in the blood. Folic acid
      supplementation is commonly used by infertile women, but the effect on pregnancy
      outcome in women with a diagnosis of unexplained infertility has not been
      thoroughly investigated. In the present study, folic acid supplement use and
      folate status (concentrations of folate and homocysteine) in women with
      unexplained infertility were evaluated in relation to pregnancy outcome. In
      addition, the use of folic acid supplements and folate status were compared
      between women with unexplained infertility and fertile control women. Our results
      showed that women with unexplained infertility used considerably more folic acid
      supplements and had higher total folic acid intake from supplements compared with
      fertile control women. Women with unexplained infertility had better blood folate
      and homocysteine concentrations than fertile women, but folic acid
      supplementation or folate status were not related to pregnancy outcome following
      the infertility treatment. In conclusion, high folic acid intake or good folate
      status did not increase the possibility of a birth of a healthy baby after
      infertility treatment in women with unexplained infertility.

PMID- 24745838
TI  - Sperm DNA damage caused by oxidative stress: modifiable clinical, lifestyle and
      nutritional factors in male infertility.
AB  - DNA fragmentation is an important factor in the aetiology of male infertility.
      However, it is still underevaluated and its inclusion in routine semen analysis
      is debated. DNA fragmentation has been shown to be a robust indicator of
      fertility potential, more so than conventional semen parameters. Men with high
      DNA fragmentation levels have significantly lower odds of conceiving, naturally
      or through procedures such as intrauterine insemination and IVF. Couples may be
      counselled to proceed directly to intracytoplasmic sperm injection as it is more
      successful in this group, avoiding costly procedures, recurrent failures or
      pregnancy losses; however, this treatment is not without limitations or risks.
      Ideally DNA fragmentation should be minimized where possible. Oxidative stress is
      the major cause of DNA fragmentation in spermatozoa. Endogenous and exogenous
      factors that contribute to oxidative stress are discussed, and in many cases are
      shown to be easily modifiable. Antioxidants play a protective role, although a
      delicate balance of reduction and oxidation is required for essential functions,
      including fertilization. Reducing oxidative stress may improve a couple's chances
      of conception either naturally or via assisted reproduction. Sources of oxidative
      stress therefore should be thoroughly examined in men with high levels of DNA
      fragmentation and modified where possible. DNA fragmentation is an important
      factor in the aetiology of male infertility. However it is still underevaluated
      and its inclusion in routine semen analysis is still debated. DNA fragmentation
      has been shown to be a robust indicator of fertility potential, more so than
      conventional semen parameters. Men with high levels of DNA fragmentation will
      have significantly lower odds of conceiving naturally or through procedures such
      as intrauterine insemination and IVF. Intracytoplasmic sperm injection (ICSI) may
      be much more successful in this group, and couples may be counselled to proceed
      directly to ICSI, avoiding costly procedures, recurrent failures or pregnancy
      losses. However, ICSI is not without its limitations or risks. Ideally, DNA
      fragmentation should be investigated and minimized where possible in men trying
      to conceive naturally or through assisted reproduction technology. Oxidative
      stress is the major cause of DNA fragmentation in spermatozoa. Endogenous and
      exogenous factors that contribute to oxidative stress are discussed and in many
      cases are easily modifiable. Antioxidants play a protective role, although a
      delicate balance of reduction and oxidation is required for essential sperm
      function, including fertilization. Reducing oxidative stress may improve a
      couple's chances of conception either naturally or via assisted reproduction
      treatment. Sources of oxidative stress therefore should be thoroughly examined in
      men with high levels of DNA fragmentation and modified where possible. 

PMID- 24745839
TI  - Randomized controlled trial of benzocaine versus placebo spray for pain relief at
      hysterosalpingogram.
AB  - Many women experience pain during hysterosalpingogram (HSG). This prospective,
      randomized, double-blinded, placebo-controlled study assessed whether the use of
      benzocaine spray during HSG is associated with reduced pain as compared with
      placebo. Thirty women presenting for HSG were enrolled and randomized to either
      benzocaine or saline spray. Treatment groups were similar in age, race, parity,
      pre-procedure oral analgesic use and history of dysmenorrhoea and/or chronic
      pelvic pain. Median change in pain score from baseline to procedure was 50.6mm (
      7.4 to 98.8mm) in the benzocaine group and 70.4mm (19.8 to 100mm) in the placebo
      group. There was no difference between groups after adjusting for history of
      dysmenorrhoea. There was no difference in resolution of pain in benzocaine versus
      placebo groups at 5 min post procedure--median pain score difference -11.1 (-90.1
      to 18.5) versus -37.0 (-100 to 1.2)--or at 30 min post procedure. Satisfaction
      scores did not differ by treatment and did not correlate with pain score during
      the procedure (rho=0.005). The use of benzocaine spray does not significantly
      improve pain relief during HSG nor does it hasten resolution of pain post HSG. Of
      interest, patient satisfaction was not correlated with pain. Many women
      experience pain during hysterosalpingogram (HSG), which is a test used to
      evaluate the uterine cavity and fallopian tube. We conducted a prospective,
      randomized, double-blinded, placebo-controlled study to assess whether the use of
      benzocaine spray during HSG is associated with reduced pain as compared with
      placebo. Thirty women presenting for HSG were enrolled and randomized to either
      benzocaine or saline spray. Treatment groups were similar in age, race, previous
      pregnancies, pre-procedure oral analgesic use and history of dysmenorrhoea
      (painful periods) and/or chronic pelvic pain. There was no difference in pain
      scores or resolution of pain between the two groups. Satisfaction scores did not
      differ by treatment group and did not correlate with the pain score during the
      procedure. We conclude that the use of benzocaine spray does not significantly
      improve pain relief during HSG nor does it hasten resolution of pain post HSG. Of
      interest, patient satisfaction was not correlated with pain.

PMID- 24745840
TI  - Predictive value of androgens and multivariate model for poor ovarian response.
AB  - No single or multivariate model is effective for predicting poor ovarian response
      (POR) with satisfactory sensitivity and specificity. This study investigated
      whether dehydroepiandrosterone sulphate (DHEAS) or basal testosterone
      concentrations could be effective predictors of POR defined by the Bologna
      criteria. This retrospective study included 79 poor responders and 128 normal
      responders. Serum FSH, LH, oestradiol, DHEAS and testosterone concentrations on
      day 3 of the menstrual cycle before the treatment cycle were measured. All
      patients received standard ovarian stimulation with FSH under pituitary
      suppression with gonadotrophin-releasing hormone agonist. DHEAS concentration was
      not significantly different between poor and normal responders or between
      pregnant and nonpregnant women. Basal testosterone, unlike DHEAS concentration,
      was predictive, but with limited ability as a single predictor, for POR. The
      multivariate model composed of age, AFC, FSH, FSH/LH and testosterone was
      reliably predictive for POR (ROC(AUC) = 0.976, cut-off point >0.51, sensitivity
      88.6%, specificity 98.3%) and clinical pregnancy (ROC(AUC) = 0.716, cut-off point
      ?-0.22, sensitivity 75%, specificity 62.5%) and was better than antral follicle
      count for predicting both POR and clinical pregnancy. This multivariate model
      might be useful for identifying patients at risk of poor response in order to
      optimize the stimulation regimens. No single or multivariate model is effective
      for predicting poor ovarian response (POR) with satisfactory sensitivity and
      specificity. It has been suggested that androgens stimulate folliculogenesis and
      their concentrations might be correlated with oocyte yield after ovulation
      induction. We investigated whether dehydroepiandrosterone sulphate (DHEAS) or
      basal testosterone concentrations could be effective predictors for POR defined
      by the Bologna criteria. This is a retrospective study with 79 poor responders
      and 128 normal responders. Serum FSH, LH, oestradiol, DHEAS and testosterone on
      day 3 of the menstrual cycle before the treatment cycle were measured. All
      patients received standard ovarian stimulation with FSH under pituitary
      suppression with gonadotrophin-releasing hormone agonist. DHEAS concentration was
      not significantly different between poor and normal responders or between
      pregnant and nonpregnant women. Basal testosterone, instead of DHEAS, was
      predictive, but with limited ability as a single predictor, for POR. However, the
      multivariate model of (0.563 * Z(age)) - (0.505 * Z(AFC)) + (0.506 * Z(FSH)) +
      (0.34 * Z(FSH/LH)) - (0.24 * Z(testosterone)) (Z(Xi) = standardized values of
      variables) was reliably predictive for POR (ROC(AUC) = 0.976) and pregnancy
      (ROC(AUC) = 0.716) and was better than antral follicle count for predicting both
      POR and pregnancy. This multivariate model composed of age, AFC, FSH, FSH/LH and
      testosterone might be useful for identifying patients at risk of poor response in
      order to optimize the stimulation regimens.

PMID- 24745841
TI  - Preparation of poly(butyl methacrylate-co-ethyleneglyceldimethacrylate)
      monolithic column modified with beta-cyclodextrin and nano-cuprous oxide and its
      application in polymer monolithic microextraction of polychlorinated biphenyls.
AB  - A poly(butyl methacrylate-co-ethyleneglyceldimethacrylate) (poly(BMA-EDMA))
      monolithic column was prepared with in situ polymerization method and modified
      with allylamine-beta-cyclodextrin (ALA-beta-CD) and nano-cuprous oxide (Cu2O). A
      polymer monolith microextraction method was developed with the modified
      monolithic column for the preconcentration of polychlorinated biphenyls combined
      with gas chromatography-electron capture detector. Various parameters affecting
      the extraction efficiency were investigated and optimized. Under the optimum
      experimental conditions, we obtained acceptable linearities, low limits of
      detection, and good intra-day/inter-day relative standard deviations. Because of
      the hydrophobic properties of beta-CD and the porous nano structure of Cu2O, the
      enrichment capacity of the poly(BMA-EDMA) monolithic column was significantly
      improved. The extraction efficiency followed the order: poly(BMA-EDMA-ALA-beta-CD
      Cu2O)>poly(BMA-EDMA-ALA-beta-CD)>poly(BMA-EDMA)>direct GC analysis. When applied
      to the determination of polychlorinated biphenyls in wine samples, low limits of
      detection (0.09ngmL(-1)) were obtained under the preoptimized conditions (sample
      volume 1.0mL, sample flow rate 0.1mLmin(-1), eluent volume 0.1mL, and eluent flow
      rate 0.05mLmin(-1)). In addition, the present method was employed to determine
      polychlorinated biphenyls in red wine samples and the accuracy was assessed
      through recovery experiments. The obtained recovery values were in the range of
      78.8-104.1% with relative standard deviations less than 9.0%. 

PMID- 24745842
TI  - Increasing the sensitivity of headspace analysis of low volatility solutes
      through water removal by hydrate formation.
AB  - This paper reports on the development of a new headspace analytical technique
      that is based on water removal by hydrate formation (WRHF). By adding anhydrous
      salt, the liquid water in an aqueous sample will be removed leaving behind
      volatile analytes that are fully vaporized at temperatures well below their
      boiling points. With WRHF, the amount of sample in the headspace can be
      significantly increased, thereby dramatically improving the detection
      sensitivity. The technique reduces the risk of possible column damage in gas
      chromatography (GC) systems. The technique was applied to the determination of
      phenol at different stages of a coking wastewater treatment plant. The results
      showed that up to mL-levels of sample solution can be used in WRHF HS-GC analysis
      when 5g of CaCl2 were used as the anhydrous salt. The detection sensitivity for
      phenol content was 500 times greater than that in earlier HS-GC work that did not
      incorporate hydrate formation. The proposed WRHF headspace analysis technique is
      simple and practical, making it a useful tool for quantifying low concentrations
      of volatile analytes in aqueous samples. 

PMID- 24745843
TI  - Carbon coated titanium dioxide nanotubes: synthesis, characterization and
      potential application as sorbents in dispersive micro solid phase extraction.
AB  - In this article, carbon coated titanium dioxide nanotubes (c-TNTs) have been
      synthesized. The synthesis of the bare TNTs (b-TNTs) using anatase as precursor
      and their coating with a caramel layer have been performed by simple and cheap
      hydrothermal processes. The final conversion of the caramel layer in a carbon
      coating has been accomplished by a thermal treatment (600 degrees C) in an inert
      (Ar) atmosphere. The c-TNTs have been characterized by different techniques
      including transmission microscopy, infrared spectroscopy, X-ray powder
      diffraction, thermogravimetry and Brunauer, Emmett and Teller (BET) adsorption
      isotherms. The extraction performance of the c-TNTs under a microextraction
      format has been evaluated and compared with that provided by b-TNTs and
      multiwalled carbon nanotubes (MWCNTs) using naproxen and ketoprofen as model
      analytes. c-TNTs provided better results than the other nanoparticles, especially
      at low acidic pH values. In addition, c-TNTs presented a better dispersibility
      than MWCNTs, which is very interesting for their use in dispersive micro-solid
      phase extraction. Finally, a microextraction format, adapted to low sample
      volumes, has been proposed and applied for the determination of naproxen and
      ketoprofen in saliva and urine samples by liquid chromatography with UV
      detection. The results indicate that this approach is promising for the analysis
      of biological samples. In fact, the recoveries were in the range between 96% and
      119% while the precision, expressed as relative standard deviation, was better
      than 8.5% and 26.3% for urine and saliva, respectively. The detection limits were
      in the range 34.1-40.8MUg/L for saliva samples and 81.1-110MUg/L for urine
      samples. 

PMID- 24745844
TI  - Multiresidue analysis of fluoroquinolone antimicrobials in chicken meat by
      molecularly imprinted solid-phase extraction and high performance liquid
      chromatography.
AB  - This paper describes the synthesis of novel molecularly imprinted polymer (MIP)
      micro-beads for the selective extraction (MISPE) of six fluoroquinolone (FQ)
      antibiotics (enrofloxacin, ciprofloxacin, lomefloxacin, danofloxacin,
      sarafloxacin and norfloxacin) from chicken muscle samples and further analysis by
      high-performance liquid chromatography (HPLC) with fluorescence (FLD) or mass
      spectrometry (MS) detection. A combinatorial screening approach has been applied
      to select the optimal functional monomer and cross-linker formulation for polymer
      synthesis. The MIP prepared using enoxacin (ENOX) as the template - a mixture of
      methacrylic acid (MAA) and trifluoromethacrylic acid (TFMAA) as functional
      monomers and ethylene glycol dimethacrylate (EDMA) as the cross-linker - showed
      superior FQ recognition properties than the rest of the materials generated. MIP
      spherical particles were prepared using silica beads as sacrificial scaffolds.
      The polymers were packed in solid phase extraction (SPE) cartridges. The
      optimized MISPE-HPLC method allows the extraction of the antimicrobials from
      aqueous samples followed by a selective washing with acetonitrile/water (0.005%
      TFA, pH=3.0), 20:80 (v/v) and elution with 5% trifluoroacetic acid in methanol.
      Optimum MISPE conditions led to recoveries of the target FQs in chicken muscle
      samples ranging between 68 and 102% and precisions in the 3-4% range (RSD, n=18).
      The method has been validated according to European Union Decision 2002/657/EC,
      in terms of linearity, accuracy, precision, selectivity, decision limit (CCalpha)
      and detection capability (CCbeta) by HPLC-FLD and HPLC-MS/MS. The limits of
      detection were improved using HPLC-MS/MS analysis and ranged between 0.2 and
      2.7MUgkg(-1) (S/N=3) for all the FQs tested. 

PMID- 24745845
TI  - Quaternized cellulose-supported gold nanoparticles as capillary coatings to
      enhance protein separation by capillary electrophoresis.
AB  - Gold nanoparticles (Au NPs) were synthesized and stabilized by using water
      soluble quaternized cellulose (QC) as support matrix through a straightforward
      and environmentally friendly aqueous-phase approach. The structure and morphology
      of QC-supported Au NPs (QC-Au NPs) were investigated systematically by UV
      visible, FT-IR, x-ray diffraction and TEM measurement. The Au NPs with mean
      diameter of about 7nm were shown to efficiently redisperse in water due to the
      strong interaction between QC and Au NPs, and the solutions were quite stable
      after storage for nearly 4 months at room temperature. QC-Au NPs were
      subsequently used as novel physically adsorbed coatings for protein separation by
      CE. The separation performance was significantly improved in the capillary coated
      by QC-Au NPs compared with that of the uncoated capillary or QC coated capillary.
      A small quantity of Au NPs (Au content of 4.6%) was adequate for the obvious
      improvement of coating ability. The theoretical plate number of lysozyme in QC
      Au1 NPs coated capillary was 2.9 times as much as that in QC coated capillary. We
      have demonstrated the separation of six model proteins with RSD of migration time
      less than 2.79% and RSD of peak area less than 4.81%. Furthermore, QC-Au NPs was
      applied to the analysis of closely related proteins and biological samples. With
      simplicity, high resolution and reproducibility, the proposed method shows
      potential for applications in proteomics and clinical diagnosis. 

PMID- 24745846
TI  - Separation performance of cucurbit[8]uril and its coordination complex with
      cadmium (II) in capillary gas chromatography.
AB  - Here we report the investigation of using cucurbit[8]uril (CB8) and its
      coordination complex with cadmium (II) (CB8-Cd) as stationary phases for
      capillary gas chromatography (GC). The prepared capillary columns of CB8 and CB8
      Cd stationary phases achieved column efficiency of 2200plates/m and 1508plates/m,
      respectively, and showed weak polarity based on the measured McReynolds
      constants. Their separation performance was investigated by GC separation of
      mixtures of different types while a commercial column was used for comparison.
      The CB8 stationary phase achieved high resolution for a wide range of analytes
      from nonpolar to polar while the CB8-Cd stationary phase exhibited good
      separation mainly for nonpolar to weak polar analytes. The CB stationary phases
      differ from the commercial one in terms of retention behaviors and resolving
      ability due to their different molecular interactions with analytes. Moreover,
      energy effect on the retention of analytes on CB8 and CB8-Cd stationary phases
      was examined, showing that retention on CB8 column was determined mainly by
      enthalpy change for polar analytes and by both enthalpy change and entropy change
      for weak polar analytes whereas retention on CB8-Cd column was mainly controlled
      by entropy change. This work demonstrates the great potential of CB8 and CB8-Cd
      stationary phases as a new type of GC stationary phases in GC analysis. 

PMID- 24745847
TI  - Polymer monoliths with chelating functionalities for solid phase extraction of
      metal ions from water.
AB  - Simple devices for the adsorption and preconcentration of metal ions comprising
      various monolithic polymers have been prepared by in situ polymerization within
      the 5.5cm long and 5.6mm i.d. polypropylene syringes. Poly(glycidyl methacrylate
      co-ethylene dimethacrylate) monolith was modified with ethylenediamine to obtain
      the chelating material. The poly(butyl methacrylate-co-ethylene dimethacrylate)
      and poly(lauryl methacrylate-co-ethylene dimethacrylate) monoliths were first
      photografted with glycidyl methacrylate prior to functionalization with
      ethylenediamine. Alternatively, other chelating functionalities including
      poly(ethylene imines) varying in molecular weight and shape (linear and branched)
      as well as lysozyme were also attached to the monolithic supports. We found that
      the poly(glycidyl methacrylate-co-ethylene dimethacrylate) monolith
      functionalized with ethylenediamine exhibited the best chelating properties
      characterized with rapid adsorption and a capacity of 111.2mg/g (537MUmol/g) for
      Pb(2+), 38.1mg/g (649MUmol/g) for Ni(2+), 69.9mg/g (1100MUmol/g) for Cu(2+), and
      188.9mg/g (3633MUmol/g) for Cr(3+). The very fast desorption was then achieved
      using 1.0mol/L HNO3 as the eluent. An enrichment factor of 300 was observed for
      metal ions adsorbed from solutions containing 2ppb of the metal. 

PMID- 24745848
TI  - PLA2G6-associated neurodegeneration (PLAN): further expansion of the clinical,
      radiological and mutation spectrum associated with infantile and atypical
      childhood-onset disease.
AB  - Phospholipase A2 associated neurodegeneration (PLAN) is a major phenotype of
      autosomal recessive Neurodegeneration with Brain Iron Accumulation (NBIA). We
      describe the clinical phenotypes, neuroimaging features and PLA2G6 mutations in 5
      children, of whom 4 presented with infantile neuroaxonal dystrophy (INAD). One
      other patient was diagnosed with the onset of PLAN in childhood, and our report
      highlights the diagnostic challenges associated with this atypical PLAN subtype.
      In this series, the neuroradiological relevance of classical PLAN features as
      well as apparent claval hypertrophy' is explored. Novel PLA2G6 mutations were
      identified in all patients. PLAN should be considered not only in patients
      presenting with a classic INAD phenotype but also in older patients presenting
      later in childhood with non-specific progressive neurological features including
      social communication difficulties, gait disturbance, dyspraxia, neuropsychiatric
      symptoms and extrapyramidal motor features. 

PMID- 24745849
TI  - National Institutes of Health (NIH) review of evidence in phenylalanine
      hydroxylase deficiency (phenylketonuria) and recommendations/guidelines for
      therapy from the American College of Medical Genetics (ACMG) and Genetics
      Metabolic Dietitians International (GMDI).

PMID- 24745850
TI  - Improvements to single particle ICPMS by the online coupling of ion exchange
      resins.
AB  - Single particle ICPMS (SP-ICPMS) is becoming a very promising technique for
      nanoparticle detection and characterization, especially at very low
      concentrations (~10(-12)-10(-10) M). Nonetheless, the ability of the technique to
      detect smaller nanoparticles is presently limited by the setting of threshold
      values for the discrimination of nanoparticles from the dissolved metal
      background. In this study, a new approach to attaining lower particle size
      detection limits has been developed by the online coupling of an ion exchange
      column (IEC) with SP-ICPMS (IEC-SP-ICPMS). The IEC effectively removes the
      continuous signal of dissolved metal, allowing for both lower detection limits
      and an improved resolution of solutions containing multiple particles. The
      feasibility and the efficiency of this coupling were investigated using silver
      nanoparticles in the presence of various concentrations of Ag(+) and other major
      ions (Mg(2+), Ca(2+), Na(+), K(+), and Cl(-)). The online elimination of the
      dissolved metal made data processing simpler and more accurate. Following the
      addition of 1 to 4 MUg L(-1) of Ag(+) spikes, symmetric particle size
      distributions were obtained using IEC-SP-ICPMS, whereas the use of SP-ICPMS alone
      led to asymmetric distributions, especially for nanoparticle sizes below 60 nm.
      Although this proof of principle study focused on nanosilver, the technique
      should be particularly useful for any of the metal based nanoparticles with high
      solubilities.

PMID- 24745852
TI  - Spinal anaesthesia for caesarean section: an ultrasound comparison of two
      different landmark techniques.
AB  - BACKGROUND: Spinal anaesthesia performed at levels higher than the L3-4
      intervertebral space may result in spinal cord injury. Our aim was to establish a
      protocol to reduce the chance of spinal anaesthesia performed at or above L2-3.
      METHODS: One hundred and ten consenting patients at 32weeks of gestation or
      greater scheduled for non-emergency caesarean section under spinal anaesthesia
      were randomly allocated to have needle insertion performed at an intervertebral
      space determined by one of two landmark techniques. In Group A, if the
      intercristal line intersected an intervertebral space, this space was selected or
      if the intercristal line intersected a spinous process the space immediately
      above was selected. In Group B, if the intercristal line intersected an
      intervertebral space or a spinous process, the intervertebral space immediately
      below was chosen. The actual intervertebral space chosen was identified using
      ultrasound by a blinded investigator. RESULTS: In Group A, an intervertebral
      space at or above L2-3 was marked in 25 (45.5%) patients compared with 4 (7.3%)
      in Group B (P <0.001). In 5/55 (9.1%) patients in Group A, the intervertebral
      space initially chosen was L1-2 whereas this occurred in no patient in Group B.
      There was no difference between groups in number of needle passes or attempts,
      onset of block at 5, 10 and 15min or need for rescue analgesia. CONCLUSION: Our
      data suggest that when performing spinal anaesthesia in pregnant patients, if the
      intercristal line intersects an intervertebral space then the space below should
      be chosen and if the intercristal line intersects a spinous process then the
      interspace below should be chosen. This will reduce the incidence of spinal
      anaesthesia performed at or above L2-3.

PMID- 24745851
TI  - Preparation and in vitro characterization of pluronic-attached polyamidoamine
      dendrimers for drug delivery.
AB  - CONTEXT: Polyamidoamine (PAMAM) dendrimers have attracted lots of interest as
      drug carriers. And little study about whether pluronic-attached PAMAM dendrimers
      could be potential drug delivery systems has been carried on. OBJECTIVE: Pluronic
      F127 (PF127) attached PAMAM dendrimers were designed as novel drug carriers.
      METHODS: Two conjugation ratios of PF127-attached PAMAM dendrimers were
      synthesized. (1)H nuclear magnetic resonance ((1)H-NMR), Fourier transform
      infrared spectrum (FTIR), element analysis and ninhydrin assay were used to
      characterize the conjugates. Size, zeta potential and critical micelle
      concentrations (CMC) were also detected. And DOX was incorporated into the
      hydrophobic interior of the conjugates. Studies on their drug loading and drug
      release were carried on. Furthermore, hemolysis and cytotoxicity assay were used
      to evaluate the toxicity of the conjugates. RESULTS AND DISCUSSION: PF127 was
      successfully conjugated to the fifth generation PAMAM dendrimer at two molar
      ratios of 19% and 57% (PF127 to surface amine per PAMAM dendrimer molecular). The
      conjugates showed an increased size and a reduced zeta potential. And higher CMC
      values were obtained than pure PF127. Compared with unconjugated PAMAM dendrimer,
      PF127 conjugation significantly reduced the hemolytic toxicity and cytotoxicity
      of PAMAM dendrimer in vitro. The encapsulation results showed that the ability to
      encapsulate DOX by the conjugate of 19% conjugation ratio was better than that of
      57% conjugation ratio. And the maximum is ~12.87 DOX molecules per conjugate
      molecule. Moreover, the complexes showed a sustained release behavior compared to
      pure DOX. CONCLUSION: Findings from the in vitro study show that the PF127
      attached PAMAM dendrimers may be potential carriers for drug delivery.

PMID- 24745853
TI  - Detection and determination of Toxoplasma gondii seroprevalence in native Korean
      goats (Capra hircus coreanae).
AB  - Toxoplasma gondii is an important zoonotic protozoan pathogen that causes serious
      illness in immunocompromised humans and infection in animals worldwide. The
      current study was conducted for detection of T. gondii infection and
      determination of the seroprevalence of the pathogen in native Korean goats (Capra
      hircus coreanae). Analysis of a total of 610 sera samples collected from 60 herds
      between 2009 and 2011 were performed using a commercial enzyme-linked
      immunosorbent assay (ELISA) kit for detection of anti-T. gondii IgG antibodies.
      Among the animals tested, 5.1% (31/610) showed seropositivity for anti-T. gondii
      antibodies, and 38.3% (23/60) of the herds were seropositive. The prevalence
      rates between young (<1 year) and adult (>=1 and <=3 years) goats were 7.0% and
      4.1%, respectively, without statistical significance (p>0.05). Likewise, the
      prevalence rates observed during cold season (October-March) and warm season
      (April-September) were 2.9% and 5.5%, respectively, without statistical
      significance. Seroprevalence rates observed in the northern, central, and
      southern regions were 7.9%, 3.8%, and 4.2%, respectively. In conclusion, we
      report for the first time on the seroprevalence of anti-T. gondii antibodies in
      native Korean goats (Capra hircus coreanae). The results of this study also
      indicate that there is a nationwide distribution of T. gondii infection among
      goats. Therefore, the implementation of integrated control strategies as well as
      measures for prevention and control of T. gondii infection within goats is
      recommended.

PMID- 24745855
TI  - Vaginal delivery after placental abruption and intrauterine fetal death,
      including failed cases.

PMID- 24745856
TI  - Broken heart, broken spine: a case of inverted Tako-Tsubo syndrome.

PMID- 24745854
TI  - Understanding and preventing drug-drug and drug-gene interactions.
AB  - Concomitant administration of multiple drugs can lead to unanticipated drug
      interactions and resultant adverse drug events with their associated costs. A
      more thorough understanding of the different cytochrome P450 isoenzymes and drug
      transporters has led to new methods to try to predict and prevent clinically
      relevant drug interactions. There is also an increased recognition of the need to
      identify the impact of pharmacogenetic polymorphisms on drug interactions. More
      stringent regulatory requirements have evolved for industry to classify
      cytochrome inhibitors and inducers, test the effect of drug interactions in the
      presence of polymorphic enzymes, and evaluate multiple potentially interacting
      drugs simultaneously. In clinical practice, drug alert software programs have
      been developed. This review discusses drug interaction mechanisms and strategies
      for screening and minimizing exposure to drug interactions. We also provide
      future perspectives for reducing the risk of clinically significant drug
      interactions.

PMID- 24745857
TI  - Treatment decision making in patients with arrhythmogenic right ventricular
      dysplasia/cardiomyopathy: state of the art.

PMID- 24745858
TI  - Right bundle branch block without overt heart disease predicts higher risk of
      pacemaker implantation: the study of atomic-bomb survivors.
AB  - BACKGROUND: We investigated the clinical course of complete right bundle branch
      block (RBBB) or RBBB with axis deviation (AD) in terms of subsequent pacemaker
      implantation for high-degree atrioventricular (AV) block or sick sinus syndrome
      (SSS). METHODS AND RESULTS: Among the 16,170 atomic-bomb survivors in our
      biennial health examination between July 1967 and December 2010, we detected 520
      newly-acquired RBBB subjects with no organic heart disease, and selected 1038 age
      (at RBBB diagnosis) and sex-matched subjects without RBBB to serve as comparison
      subjects. Multivariate Cox regression analysis was used to estimate the hazard
      ratios (HRs) for the risk of pacemaker implantation due to all causes, AV block
      or SSS between RBBB and comparison subjects and between RBBB subjects with and
      without AD. The risk of pacemaker implantation for RBBB was 4.79 (95% confidence
      interval [CI] 1.89-12.58; P=0.001), 3.77 (95% CI, 1.09-13.07; P=0.036), and 6.28
      (95% CI, 1.24-31.73, P=0.026) when implantation was for all causes, AV block and
      SSS, respectively. RBBB subjects with AD had a higher risk for all-cause
      pacemaker implantation than subjects without AD (HR, 3.03; 95% CI, 1.00-9.13,
      P=0.049). RBBB subjects with AD were younger than subjects without AD at the time
      of RBBB diagnosis (59.4+/-7.6 vs 74.4+/-3.1 years old, P=0.019), and their
      progression from diagnosis to pacemaker implantation took longer (15.1+/-6.6 vs
      6.4+/-3.0 years, P=0.032). CONCLUSIONS: RBBB, especially with AD, progresses to
      AV block and SSS that requires pacemaker implantation; the mechanisms by which
      the conduction defect progresses differ among patients with and without AD.

PMID- 24745859
TI  - High-density lipoprotein cholesterol and risk of cardiovascular events in
      octogenarian patients with acute coronary syndrome: long-term follow-up study.

PMID- 24745860
TI  - Hypertriglyceridemic waist phenotype and risk of cardiovascular diseases in
      China: results from the Kailuan Study.
AB  - BACKGROUND: While some case-control studies have showed the correlation between
      the hypertriglyceridemic waist (HTGW) phenotype (increased WC and
      hypertriglyceridemia) and cardiovascular disease (CVD) events, there are few data
      regarding this correlation in cohort studies, especially in Asian populations
      that have a higher prevalence of central obesity than other populations.
      OBJECTIVE: The aim of this study was to explore the relationship between HTGW
      phenotype and risk of incident CVD events among men and women in China. METHODS:
      We analyzed 95,015 participants (18-98 years old) in the Kailuan Study. CVDs
      developed in 1958 people during follow-up. The cutoffs for defining HTGW
      phenotype were a waist circumference (WC) of 90 cm or more and a triglyceride
      level of 2.0 mmol/L or more for men and a WC of 85 cm or more and a triglyceride
      level of 1.5 mmol/L or more for women. Hazard ratios (HRs) with 95% confidence
      intervals (CIs) were calculated from Cox regression models. RESULTS: Compared
      with participants who had a normal WC and a normal triglyceride level (NWNT),
      those with HTGW phenotype had a higher WC, body mass index, prevalence of
      hypertension and diabetes mellitus; and a lower level of high-density lipoprotein
      cholesterol. The HTGW group had an unadjusted HR of 1.76 (95% CI=1.55-1.99) for
      future CVDs compared with the NWNT group. After adjustment for confounders, the
      HR still remained significant (HR=1.24, 95% CI=1.07-1.44). CONCLUSIONS: HTGW
      phenotype was associated with the risk of CVDs independently. HTGW phenotype
      might be a simple but useful tool to screen the individuals at a high risk for
      future CVDs, and it might be recommended in most clinical practices.

PMID- 24745861
TI  - Simple and safe percutaneous retrieval of an embolized coil by using a flexible 3
      F microforceps--a technical case report.

PMID- 24745862
TI  - Extending single-molecule microscopy using optical Fourier processing.
AB  - This article surveys the recent application of optical Fourier processing to the
      long-established but still expanding field of single-molecule imaging and
      microscopy. A variety of single-molecule studies can benefit from the additional
      image information that can be obtained by modulating the Fourier, or pupil, plane
      of a widefield microscope. After briefly reviewing several current applications,
      we present a comprehensive and computationally efficient theoretical model for
      simulating single-molecule fluorescence as it propagates through an imaging
      system. Furthermore, we describe how phase/amplitude-modulating optics inserted
      in the imaging pathway may be modeled, especially at the Fourier plane. Finally,
      we discuss selected recent applications of Fourier processing methods to measure
      the orientation, depth, and rotational mobility of single fluorescent molecules. 

PMID- 24745864
TI  - Acupuncture in the management of acute dental pain.
AB  - Acute dental pain is the main reason for seeking dental services to provide
      urgent dental care; there is consensus about the use of alternative therapies,
      such as acupuncture, to control dental pain in pre-dental care. This study aimed
      to evaluate the use of acupuncture in reducing the intensity of acute dental pain
      in pre-dental care in patients waiting for emergency dental care, and was
      conducted at the After-Hours Emergency Dental Clinic of Piracicaba Dental School,
      and at the Emergency Center Dental Specialties I in Piracicaba, Sao Paulo,
      Brazil. The sample consisted of 120 patients. The Visual Analog Scale (VAS) was
      used to measure pain intensity. All patients underwent one session of
      acupuncture; the points LI4, ST44 and CV23 were selected and were used alone or
      in combinations. Reduction in pain was observed in 120 patients (mean initial
      VAS=6.558+/-1.886, p<0; mean final VAS=0.962+/-2.163, p<0.00001). The results of
      this study indicate that acupuncture analgesia could be a technical adjunct to
      pain control in patients with acute dental pain, contributing to the restoration
      of health with social benefit.

PMID- 24745863
TI  - Randomized trial of trigger point acupuncture treatment for chronic shoulder
      pain: a preliminary study.
AB  - There is evidence for the efficacy of acupuncture treatment for chronic shoulder
      pain, but it remains unclear which acupuncture modes are most effective. We
      compared the effect of trigger point acupuncture (TrP), with that of sham (SH)
      acupuncture treatments, on pain and shoulder function in patients with chronic
      shoulder pain. The participants were 18 patients (15 women, 3 men; aged 42-65
      years) with nonradiating shoulder pain for at least 6 months and normal
      neurological findings. The participants were randomized into two groups, each
      receiving five treatment sessions. The TrP group received treatment at trigger
      points for the muscle, while the other group received SH acupuncture treatment on
      the same muscle. Outcome measures were pain intensity (visual analogue scale,
      VAS) and shoulder function (Constant-Murley Score: CMS). After treatment, pain
      intensity between pretreatment and 5 weeks after TrP decreased significantly
      (p<0.001). Shoulder function also increased significantly between pretreatment
      and 5 weeks after TrP (p<0.001). A comparison using the area under the outcome
      curves demonstrated a significant difference between groups (p=0.024). Compared
      with SH acupuncture therapy, TrP therapy appears more effective for chronic
      shoulder pain.

PMID- 24745865
TI  - Acupuncture in preventing postoperative nausea and vomiting: efficacy of two
      acupuncture points versus a single one.
AB  - Despite recent advances in anesthesiology and postoperative care, postoperative
      nausea and vomiting are common complaints. Although acupuncture techniques have
      received attention in anesthesiology, the ideal technique and selection of the
      most appropriate acupuncture points are still under debate. This study compared
      the efficacy of two simultaneous acupuncture points with that of a single point
      in the prevention and treatment of postoperative nausea and vomiting following
      general anesthesia through a double-blind, randomized, controlled trial involving
      227 surgical patients undergoing general anesthesia who were randomly assigned
      into two groups. The first group received acupuncture by stimulation only on the
      PC6 point (single group), and the second group underwent concomitant stimulation
      of the PC6 and the L14 acupuncture points (combined group) during surgery under
      general anesthesia. The prevalences of postoperative nausea and vomiting were
      compared between the two groups. No significant differences were observed between
      the two groups (p>0.05). Of 115 patients in the combined group, 80 (69.6%)
      complained about nausea and vomiting compared with 96 (85.7%) in the single
      group, a significantly lower proportion (p<0.05). Our findings favor a
      combination of PC6 and LI4 stimulation for the treatment of postoperative nausea
      and vomiting.

PMID- 24745866
TI  - Direct moxibustion to treat spleen qi and yang deficiency fatigue: a pilot study.
AB  - Limited research suggests that indirect moxibustion may be beneficial for
      treating fatigue, but no studies to evaluate direct moxibustion have been
      conducted in the United States. Thus, we explored the usefulness of four outcome
      measures for evaluating the effectiveness of direct moxibustion for patients with
      spleen qi and yang deficiency fatigue (SQYDF). Eleven female volunteers, ages 25
      60 years, were enrolled. Three to five rice grains in thread-sized moxa cones
      were burned on 11 acupuncture points once per week for 8 weeks. Eight
      participants completed the study. The most common adverse events (AEs) were
      temporary worsening of fatigue, lightheadedness, and headache. Symptomatic
      improvement was seen on the SF-36 energy/fatigue scale (p=0.003), SF-36 social
      function scale (p=0.008) and Flinders fatigue scale (p=0.014). The skin
      conductance at acupoints showed no consistent diagnostic baseline meridian
      patterns. Heart rate variability data showed an improved low frequency/high
      frequency (LF/HF) ratio in three of four participants. Direct moxibustion is safe
      in patients with SQYDF. The Flinders Fatigue Scale (FFS) and the SF-36 are useful
      outcome measures for evaluating the effects of direct moxibustion, and the heart
      rate variability (HRV) may be, but the skin conductance did not correlate with
      SQYDF diagnosis or with symptomatic improvement.

PMID- 24745867
TI  - Effects of intermittent traction therapy in an experimental spinal column model.
AB  - Traction therapy, which is known to be a treatment method for scoliosis, one of
      many muscles disease, has been used since Hippocrates introduced it. However, the
      effects of traction therapy are still not clear. In addition, the meridian sinew
      theory, which is related to muscle treatment and is mentioned in the book on
      meridian sinews in the Miraculous Pivot of Huangdi's Internal Classic, has not
      been the subject of much study. For these reasons, experimental spinal models
      were made for this study to observe and analyze the lengths of vertebral
      interspaces after intermittent traction therapy, which is known to be excellent
      among muscle treatment methods, with various tensile forces. The results showed
      that the effects of intermittent traction therapy were unclear and that it might
      be harmful, especially when the pain was induced by muscle weakness. Because the
      results of this study on intermittent traction therapy were different from those
      expected from osteopathy or craniosacral theory, better studies of the subject
      are necessary. 

PMID- 24745868
TI  - Possible role of epidermal keratinocytes in the construction of acupuncture
      meridians.
AB  - Acupuncture meridians consist of a network of acupuncture points on the skin,
      stimulation of which is well established to have a variety of physiological
      effects. We have previously demonstrated that epidermal keratinocytes contain
      multiple sensory systems for temperature, mechanical stimuli, electric potentials
      and other stimuli. These sensory systems generate changes in the calcium-ion
      concentration in the epidermis, so epidermal keratinocytes can generate spatially
      localized electro-physiological patterns in the skin. We have previously
      demonstrated signaling between epidermal keratinocytes and peripheral nerve
      systems. Therefore, stimuli sensed by epidermal keratinocytes might be
      transferred to the unmyelinated nerve fibers that are known to exist in the
      epidermis and, thence, to the spinal cord and brain. We propose that epidermal
      keratinocytes form an information-gathering network in the skin and that this
      network plays a key role in whole-body homeostasis in response to the changing
      environment. We also hypothesize that this network corresponds to the acupuncture
      meridians. As supporting examples, we present some striking calcium propagation
      patterns observed in cultured human keratinocytes after adenosine-triphosphate
      (ATP) stimulation. These results support the ideas that keratinocytes can
      generate spatially-restricted signaling patterns after environmental stimulation
      and that the cultures might be in-vitro models of meridians as an information
      gathering network in skin. 

PMID- 24745869
TI  - A case study of pigmentation and textural changes associated with needling Yin
      Tang.
AB  - In this article, a case is presented in which repeated needling of the Yin Tang
      point over the course of 6 years was perceived to cause pigmentation and textural
      changes to the skin. Others have reported changes to pigmentation, but those
      changes were either shorter lived and associated with strong stimulation, or were
      associated with implanting a silver needle for several years. 

PMID- 24745870
TI  - Evaluation of spiritual needs of patients with advanced cancer in a palliative
      care unit.
AB  - INTRODUCTION: Spiritual needs play an important role in palliative care as both a
      clinical dimension and a therapeutic strategy. However, recent studies have shown
      that the management of this dimension still remains a challenge at the clinical
      level of palliative care. GOALS: Our goal was to evaluate the spiritual needs of
      patients diagnosed with advanced and terminal cancer by the palliative care unit
      of a hospital in Barcelona, Spain. METHODS: An observational study was conducted
      that involved 50 patients who were recruited between May 2007 and January 2008. A
      questionnaire was used which included 28 items selected from a review of the
      literature; the responses were analyzed using a five-point Lickert scale. The
      results were grouped in 11 categories corresponding to different spiritual needs.
      RESULTS: Two spiritual needs emerged as the most relevant for the patients: their
      need to be recognized as a person until the end of their life and their need to
      know the truth about their illness. The least important spiritual needs were
      identified as those: for continuity and an afterlife; to get rid of obsessions;
      to achieve freedom from blame and to be able to forgive others; and the need for
      reconciliation and to feel forgiven by others. CONCLUSIONS: When patients knew
      the truth about their illnesses and they were treated with dignity, their most
      important needs were likely to be covered. These results suggest that patients
      receiving palliative care wish to live for the present with as much normality as
      possible and show only minor concern for their past and future.

PMID- 24745871
TI  - Wet-chemical enzymatic preparation and characterization of ultrathin gold
      decorated single glass nanopore.
AB  - The conical glass nanopore was modified through layer-by-layer electrostatic
      deposition of a monolayer of glucose oxidase, and then an ultrathin gold film was
      formed in situ through enzyme-catalyzed reactions. The morphology and components
      of single glass nanopore before and after ultrathin Au deposition were
      characterized by transmission electron microscopy (TEM) and energy-dispersive X
      ray (EDX) analysis, respectively. In particular, the quenching of the quantum
      dots fluorescence in the nanopore tip zone further illustrated that the gold
      nanofilm was successfully deposited on the inner wall of the single glass
      nanopore. The Au thin films make the glass nanopores more biologically friendly
      and allow the nanopores facile functionalization of the surface through the Au-S
      bonds. For instance, the ionic current rectification (ICR) properties of the gold
      decorated glass nanopores could be switched readily at different pHs by
      introducing different thiol molecules. 

PMID- 24745872
TI  - [Subacute care of stroke-affected patients. Satisfaction and results].
AB  - OBJECTIVE: To determine the satisfaction of the stroke inpatients and their
      caregivers in Rehabilitation Service and to analyze the effectiveness, social
      risk, and discharge destination. MATERIAL AND METHOD: Prospective longitudinal
      cohort multicenter study. An analysis was made of the social risk (Gijon Scale),
      co-morbidity (Charlson Index), disability (Barthel Index), effectiveness of the
      rehabilitation treatment, satisfaction (Pound Questionnaire) and discharge
      destination of 241 patients. An evaluation was also made on 119 caregivers 6
      months post-stroke, recording age, family relationship, time care-giving,
      satisfaction with the information/training, and accessibility to the
      rehabilitation team. RESULTS: The patient profile is a 71 year-old male, with
      low/intermediate social risk, high co-morbidity and total/severe dependence, with
      27.1% living alone. Almost all (96.6%) of the patients claimed to be
      satisfied/very satisfied with the treatment, with satisfaction with the recovery
      being lower (80.3%). The effectiveness was 32.5 +/- 20.4. Home was the discharge
      destination of 81.7% of the patients.The average age of the caregivers was 58.8
      +/- 12.3 years, and 73.9% were women. The time dedicated to care-giving was over
      6 hours per day in the 62% of the cases. Being satisfied/very satisfied with the
      received information was recorded by 89.9% of the caregivers. CONCLUSIONS:
      Patients admitted for stroke rehabilitation achieve significant functional gain
      during hospitalization and return to their homes in most cases. The satisfaction
      with the rehabilitation treatment and received information is high. The training
      of the caregiver is an aspect that needs improving.

PMID- 24745873
TI  - The agreement between abnormal venous lactate and arterial lactate in the ED: a
      retrospective chart review.
AB  - INTRODUCTION: The evidence for prognostication using lactate is often based on
      arterial lactate (AL). Arterial sampling is painful and difficult, and carries
      risks. Studies comparing peripheral venous lactate (PVL) with AL showed little
      difference but predominantly included patients with normal lactate. The objective
      of this study was to measure agreement between PVL and AL in patients with
      elevated venous lactate. METHODS: This is a retrospective cross-sectional study.
      INCLUSION CRITERIA: ED patients age>=16, attending from October 2010 to June 2011
      inclusive, with PVL>=2.0 mmol/L and AL taken within 1 hour. EXCLUSION CRITERIA:
      intravenous fluid prior to or between initial venous and arterial sampling.
      Primary endpoint: agreement between PVL and AL defined as mean difference+/-95%
      limits of agreement (LOA). The misclassification rate was assessed. RESULTS:
      N=232. VL median 3.50 mmol/L, range 2.00 to 15.00 mmol/L. AL median 2.45 mmol/L,
      range 1.0 to 13.2 mmol/L. The mean difference+/-SD between PVL and AL for all
      patients was 1.06+/-1.30 mmol/L (95%LOA -1.53 to 3.66 mmol/L). Using a cut-off of
      2 mmol/L and 4 mmol/L, 36.2% and 17.9% of patients respectively were incorrectly
      classified as having elevated lactate. CONCLUSION: We report greater bias between
      VL and AL with broader LOA than previously documented. This may partly be due to
      the fact that we studied only patients with abnormal venous values, for whom
      close agreement would confer greatest clinical significance. The agreement
      between abnormal PVL and AL is poor and the high rate of misclassification may
      suggest that PVL is not a good substitute for AL if the venous lactate is
      abnormal.

PMID- 24745874
TI  - Restrictive cardiomyopathy in a patient presented with fever, vomiting, and
      consciousness disorder.
AB  - Restrictive cardiomyopathy (RCM) is an uncommon form of myocardial disorder
      characterized by diastolic dysfunction and increased myocardial stiffness.
      Endomyocardial fibrosis is one type of RCM hallmarked by formation of fibrous
      tissue on the endocardium. This report describes a case of RCM confirmed by
      autopsy in a young man who presented atypically with fever, vomiting, and
      delirium.

PMID- 24745875
TI  - Identification of high-risk patients with acute coronary syndrome using point-of
      care echocardiography in the ED.
AB  - Stratifying risk of patients with acute coronary syndrome (ACS) in the emergency
      department (ED) remains a frequent challenge. When ST-elevation criteria are
      absent, current recommendations rely upon insensitive and time-intensive methods
      such as the electrocardiogram and cardiac enzyme testing. Here, we report on a
      series of cases, where emergency physicians used a simplified model for
      identifying regional wall motion abnormalities by point-of-care echocardiography
      in patients presenting with chest pain to the ED. With the use of a simplified
      model described herein, high-risk patients with ACS were identified rapidly in a
      cohort usually difficult to risk stratify. 

PMID- 24745876
TI  - Surveillance and quality improvement in the United Kingdom: is there a meeting
      point?
AB  - Recent high profile failures within the National Health Service of England and
      Wales have highlighted the need for surveillance of quality and performance.
      Mortality is the most commonly used metric, assessed at the hospital or trust
      level. However overall mortality can mask where the failures lie and even if they
      exist. Continuous surveillance at a granular level is needed, especially in
      surgery where interventions need to be safe, reliable and efficacious but so does
      the coordination of care along the entire patient pathway with robust protocols
      and mechanisms in place to prevent 'failure to rescue' and to optimise patient
      outcomes. There is an expanding body of surveillance tools available for surgical
      practice and these are beginning to show merit. The Care Quality Commission, who
      monitor services, increasingly through ongoing surveillance as well as
      inspections, should work more closely with local quality improvement efforts and
      become a vector for care excellence, actively involved with spreading best
      practice throughout the entire NHS and not just for identifying the 'bad apples'.

PMID- 24745879
TI  - WITHDRAWN: Sudden Death in the Context of an Undiagnosed Congenital Coronary
      Anomaly.

PMID- 24745881
TI  - Setting the record straight: the origin of the pharmacophore concept.
AB  - For over a century since the early 1900s, Paul Ehrlich was credited with
      originating the concept of pharmacophores. This was challenged by John Van Drie
      in 2007 due to the fact that Ehrlich did not use the word "pharmacophore" in his
      writings. Van Drie claimed that the attribution of the pharmacophore concept to
      Ehrlich was due to an erroneous citation made by Ariens in a 1966 paper, and
      instead he claimed, Lemont B. Kier developed the pharmacophore concept (in the
      modern sense, as defined by the IUPAC) during 1967-1971. There are two separate
      issues that may have triggered this conflict. The first one is the shift in the
      meaning of pharmacophore from "chemical groups" to patterns of "abstract
      features" of a molecule that are responsible for a biological effect. Indeed, the
      original use of the term is different than the current definition proposed by the
      IUPAC. The term was redefined in 1960 by Schueler, and this modification formed
      the basis of IUPAC's modern definition. The second issue is the origin of the
      "concept" of pharmacophore. While Ehrlich's contemporaries have consistently
      attributed the origin of the concept to him, the issue is further complicated by
      the fact that Ehrlich did not use the term pharmacophore in his papers. He,
      instead, referred to the features of a molecule that are responsible for
      biological effects as toxophores, while his contemporaries were using the term
      pharmacophore for the same features. In this paper, we resolve any doubts about
      the origins of the pharmacophore concept. Our research points to Paul Ehrlich's
      1898 paper for originating the concept, which identifies peripheral chemical
      groups in molecules responsible for binding that leads to the subsequent
      biological effect, and to Schueler's 1960 book that extends the concept to the
      modern definition where spatial patterns of abstract features of a molecule
      define the pharmacophore and are ultimately responsible for the biological
      effect. 

PMID- 24745882
TI  - Wilson disease: what is still unclear in pediatric patients?
AB  - Since Wilson disease (WD) may not be present with evident clinical symptoms of
      liver injury and neurological presentation is rare in children, establishing a
      diagnosis is often challenging, especially in childhood. Increased transaminases
      can be the only abnormality found in early course of WD. In clinical practice,
      high suspicion is crucial for early diagnosis and timely treatment to ensure
      better outcomes. Conventional diagnostic criteria established for adults are
      commonly agreed for children but may not always be appropriate in very young age.
      Currently, the best therapeutic approach for each specific presentation of the
      disease remains controversial and there are no clear indications about how to
      treat pediatric WD patients with a mild liver disease. 

PMID- 24745883
TI  - Hormonal profile and androgen receptor study in prepubertal girls with
      hypertrichosis.
AB  - BACKGROUND: Prepubertal hypertrichosis is a reportedly benign condition
      characterized by an excessive growth of vellous hair in non-androgen dependent
      areas of the body compared to the amount usually present in normal subjects of
      the same age, race and sex. Although this condition is usually considered
      idiopathic and regarded as benign, it may be very disturbing cosmetically,
      causing significant patient and parental anxiety. METHOD: We performed a hormonal
      and androgen receptor study in 42 prepubertal girls with hypertrichosis and 29
      control girls from 2 to 8 years of age. Both groups underwent a determination of
      basal LH, FSH, 17OH progesterone, androstenedione, testosterone, estradiol and
      SHBG, abdominal ultrasound to assess ovarian morphology, and the number of
      androgen receptor CAG/GGC repeats in DNA obtained from peripheral leukocytes.
      RESULTS: The hypertrichosis score was higher in the cases compared to controls.
      Serum gonadotropins and sex steroids were similar in both groups, but SHBG was
      significantly lower in the girls with hypertrichosis (71.1 +/- 2.9 vs 81.9 +/-
      3.0 nmol/L, p < 0.02). The distribution of shorter, larger and total alleles was
      not statistically different between cases and controls. The combined analysis of
      CAG/GGC, however, showed a significantly higher prevalence of the most androgen
      sensitive haplotypes (1-2: <22CAG + 17/17GGC- < 14CAG + 17/18GGC) in girls with
      hypertrichosis compared to controls. CONCLUSIONS: We conclude that girls with
      hypertrychosis exhibit AR(s) with enhanced sensitivity, which may facilitate the
      growth of their body hair.

PMID- 24745884
TI  - Letter from the Guest Editor: Toxic and metabolic encephalopathic syndromes:
      definition and imaging of "encephalopathy".

PMID- 24745885
TI  - Imaging of acquired metabolic and toxic disorders of the basal ganglia.
AB  - Toxic and metabolic disorders affecting the basal ganglia are variable, common,
      and easily misinterpreted on neuroimaging studies. Integration of clinical
      information with imaging findings is key to helping referring physicians diagnose
      and treat the underlying ailment. This review aims to provide a systematic
      approach to both computed tomography and magnetic resonance imaging findings,
      their potential causes, and their clinical implications. 

PMID- 24745886
TI  - Wernicke encephalopathy and ethanol-related syndromes.
AB  - Ethanol causes diverse neurologic conditions caused by acute and chronic brain
      damage. This review provides an overview of Wernicke encephalopathy and other
      ethanol-related brain changes, such as chronic brain atrophy, Marchiafava-Bignami
      disease, osmotic demyelination syndrome, chronic hepatic encephalopathy, and
      acute alcohol withdrawal. As clinical symptoms of this spectrum of diseases have
      nonspecific neurologic alterations, radiologists should have current radiologic
      information and understand the imaging findings pertaining to the pathophysiology
      to support diagnosis. 

PMID- 24745887
TI  - Toxic leukoencephalopathies, including drug, medication, environmental, and
      radiation-induced encephalopathic syndromes.
AB  - Toxic leukoencephalopathies can be secondary to the exposure to a wide variety of
      exogenous agents, including cranial irradiation, chemotherapy, antiepileptic
      agents, drugs of abuse, and environmental toxins. There is no typical clinical
      picture, and patients can present with a wide array of signs and symptoms.
      Involvement of white matter is a key finding in this scenario, although in some
      circumstances other high metabolic areas of the central nervous system can also
      be affected. Magnetic resonance (MR) imaging usually discloses bilateral and
      symmetric white matter areas of hyperintense signal on T2-weighted and fluid
      attenuated inversion recovery images, and signs of restricted diffusion are
      associated in the acute stage. In most cases, the changes are reversible,
      especially with prompt recognition of the disease and discontinuation of the
      noxious agent. Either the MR or clinical features may be similar to several
      nontoxic entities, such as demyelinating diseases, leukodystrophies, hepatic
      encephalopathy, vascular disease, hypoxic-ischemic states, and others. A high
      index of suspicion should be maintained whenever a patient presents recent onset
      of neurologic deficit, searching the risk of exposure to a neurotoxic agent.
      Getting to know the most frequent MR appearances and mechanisms of action of
      causative agents may help to make an early diagnosis and begin therapy, improving
      outcome. In this review, some of the most important causes of
      leukoencephalopathies are presented; as well as other 2 related conditions:
      strokelike migraine attacks after radiation therapy syndrome and reversible
      splenial lesions. 

PMID- 24745888
TI  - Posterior reversible encephalopathy syndrome.
AB  - Posterior reversible encephalopathy syndrome (PRES) is a complex disorder, our
      understanding of which continues to evolve. PRES has many clinical associations,
      many causative factors, a variety of imaging manifestations, and its
      pathophysiology remains a topic of debate. There are also many other disorders
      that may mimic PRES. We present a concise review of PRES to enable the
      radiologist to more readily and easily recognize this treatable disorder with
      important clinical implications. 

PMID- 24745889
TI  - Brain magnetic resonance in hepatic encephalopathy.
AB  - The term hepatic encephalopathy (HE) covers a wide spectrum of neuropsychiatric
      abnormalities caused by portal-systemic shunting. The diagnosis requires
      demonstration of liver dysfunction or portal-systemic shunts and exclusion of
      other neurologic disorders. Most patients with this condition have liver
      dysfunction caused by cirrhosis, but it also occurs in patients with acute liver
      failure and less commonly, in patients with portal-systemic shunts that are not
      associated with hepatocellular disease. Various magnetic resonance (MR)
      techniques have improved our knowledge about the pathophysiology of HE. Proton MR
      spectroscopy and T1-weighted imaging can detect and quantify accumulations of
      brain products that are normally metabolized or eliminated such as glutamine and
      manganese. Other MR techniques such as T2-weighted and diffusion-weighted imaging
      can identify white matter abnormalities resulting from disturbances in cell
      volume homeostasis secondary to brain hyperammonemia. Partial or complete
      recovery of these abnormalities has been observed with normalization of liver
      function or after successful liver transplantation. MR studies have undoubtedly
      improved our understanding of the mechanisms involved in the pathogenesis of HE,
      and some findings can be considered biomarkers for monitoring the effects of
      therapeutic measures focused on correcting this condition. 

PMID- 24745890
TI  - Osmotic demyelination syndrome: central pontine myelinolysis and extrapontine
      myelinolysis.
AB  - Osmotic demyelination syndrome (ODS) refers to central pontine myelinolysis and
      extrapontine myelinolysis. These disorders are characterized by insults to
      regions of the brain with anatomical features predisposing white matter tracts to
      myelin injury in the setting of osmotic disturbances and their attempted
      correction. Occurring independently or in combination, central pontine
      myelinolysis and extrapontine myelinolysis share a characteristic timing of
      onset, but distinct clinical features. Imaging features demonstrate
      characteristic findings that suggest ODS, but must be correlated with clinical
      features. Once thought to be universally devastating, ODS currently can have a
      variable clinical outcome. 

PMID- 24745891
TI  - Congenital genetic inborn errors of metabolism presenting as an adult or
      persisting into adulthood: neuroimaging in the more common or recognizable
      disorders.
AB  - Numerous congenital-genetic inborn errors of metabolism (CIEMs) have been
      identified and characterized in detail within recent decades, with promising
      therapeutic options. Neuroimaging is becoming increasingly utilized in earlier
      stages of CIEMs, and even in asymptomatic relatives of patients with a CIEM, so
      as to monitor disease progress and treatment response. This review attempts to
      summarize in a concise fashion the neuroimaging findings of various CIEMs that
      may present in adulthood, as well as those that may persist into adulthood,
      whether because of beneficial therapy or a delay in diagnosis. Notably, some of
      these disorders have neuroimaging findings that differ from their classic
      infantile or early childhood forms, whereas others are identical to their early
      pediatric forms. The focus of this review is their appearance on routine magnetic
      resonance imaging sequences, with some basic attention to the findings of such
      CIEMs on specialized neuroimaging, based on recent or preliminary research. The
      general classes of disorders covered in this complex review are: peroxisomal
      disorders (adrenoleukodystrophy), lysosomal storage disorders (including
      metachromatic leukodystrophy, Krabbe or globoid cell leukodystrophy, Fabry,
      Niemann-Pick, GM1, GM2, Gaucher, mucopolysaccharidoses, and Salla diseases),
      mitochondrial disorders (including mitochondrial encephalomyopathy with lactic
      acidosis and strokelike episodes, myoclonic epilepsy with ragged red fibers,
      Leigh disease, and Kearns-Sayre syndrome), urea cycle disorders, several organic
      acidemias (including phenylketonuria, maple syrup urine disease, 3-hydroxy-3
      methylglutaryl colyase deficiency, glutaric acidurias, methylmalonic academia,
      proprionic academia, 3-methylglucatonic aciduria, and 2-hydroxyglutaric
      acidurias), cytoskeletal or transporter molecule defects (including Alexander or
      fibrinoid leukodystrophy, proteolipid protein-1 defect or Pelizaeus Merzbacher,
      Wilson, and Huntington diseases), and several neurodegenerative disorders of
      brain iron accumulation. Additionally, an arbitrary "miscellaneous" category of 5
      recognizable disorders that may present in or persist into adulthood is
      summarized, which include megalencephalic leukoencephalopathy with subcortical
      cysts (megancephalic leukoencephalopathy with subcortical cysts or van der Knaap
      disease), polymerase-III gene defect ("4H syndrome"), childhood ataxia with
      central nervous system hypomyelination ("vanishing white matter disease"),
      striopallidodentate calcinosis ("Fahr disease"), and Cockayne syndrome.

PMID- 24745892
TI  - Neutrophil-lymphocyte ratio as an important assessment tool.

PMID- 24745893
TI  - Harvesting water wave energy by asymmetric screening of electrostatic charges on
      a nanostructured hydrophobic thin-film surface.
AB  - Energy harvesting from ambient water motions is a desirable but underexplored
      solution to on-site energy demand for self-powered electronics. Here we report a
      liquid-solid electrification-enabled generator based on a fluorinated ethylene
      propylene thin film, below which an array of electrodes are fabricated. The
      surface of the thin film is charged first due to the water-solid contact
      electrification. Aligned nanowires created on the thin film make it hydrophobic
      and also increase the surface area. Then the asymmetric screening to the surface
      charges by the waving water during emerging and submerging processes causes the
      free electrons on the electrodes to flow through an external load, resulting in
      power generation. The generator produces sufficient output power for driving an
      array of small electronics during direct interaction with water bodies, including
      surface waves and falling drops. Polymer-nanowire-based surface modification
      increases the contact area at the liquid-solid interface, leading to enhanced
      surface charging density and thus electric output at an efficiency of 7.7%. Our
      planar-structured generator features an all-in-one design without separate and
      movable components for capturing and transmitting mechanical energy. It has
      extremely lightweight and small volume, making it a portable, flexible, and
      convenient power solution that can be applied on the ocean/river surface, at
      coastal/offshore areas, and even in rainy places. Considering the demonstrated
      scalability, it can also be possibly used in large-scale energy generation if
      layers of planar sheets are connected into a network. 

PMID- 24745894
TI  - Breakdown of interference rules in azulene, a nonalternant hydrocarbon.
AB  - We have designed and synthesized five azulene derivatives containing gold-binding
      groups at different points of connectivity within the azulene core to probe the
      effects of quantum interference through single-molecule conductance measurements.
      We compare conducting paths through the 5-membered ring, 7-membered ring, and
      across the long axis of azulene. We find that changing the points of connectivity
      in the azulene impacts the optical properties (as determined from UV-vis
      absorption spectra) and the conductivity. Importantly, we show here that simple
      models cannot be used to predict quantum interference characteristics of
      nonalternant hydrocarbons. As an exemplary case, we show that azulene derivatives
      that are predicted to exhibit destructive interference based on widely accepted
      atom-counting models show a significant conductance at low biases. Although
      simple models to predict the low-bias conductance do not hold with all azulene
      derivatives, we demonstrate that the measured conductance trend for all molecules
      studied actually agrees with predictions based on the more complete GW
      calculations for model systems. 

PMID- 24745895
TI  - Preparation of tetrasubstituted 3-phosphonopyrroles through hydroamination: scope
      and limitations.
AB  - Phosphonylated pyrroles were obtained by a ZnCl2-catalyzed 5-exo-dig
      hydroamination of propargylic enamines. These starting compounds were obtained in
      two steps from commercially available beta-ketophosphonates. The method tolerates
      a wide variety of substituents at the 1,2- and 5-position of the pyrrole, while
      further derivatization allows for the introduction of substituents at the 4
      position via lithiation or halogenation. 

PMID- 24745896
TI  - Long-term effect on membrane fouling in a new membrane bioreactor as a
      pretreatment to seawater desalination.
AB  - Submerged membrane adsorption bio-reactors (SMABR) were investigated as a new
      pretreatment for seawater reverse osmosis (SWRO) desalination. They were tested
      with different doses of powder activated carbon (PAC) on-site for a long-term.
      The biofouling on the membrane was assessed in terms of DNA (cells) and
      polysaccharide distribution. MBR without PAC addition resulted in severe fouling
      on membrane. When PAC is added in the MBR, PAC could reduce the organic fouling.
      Hence the biofilm formation on membrane was reduced without any membrane damage.
      PAC also helped to remove low molecular weight (LMW) organics responsible for
      biofouling of RO membrane. A linear correlation between assimilable organic
      carbon (AOC) and LMW organics was observed. A small amount of PAC (2.4-8.0g of
      PAC/m(3) of seawater) was sufficient to reduce biofouling. It indicated that
      SMABR is an environmentally-friendly biological pretreatment to reduce biofouling
      for SWRO. 

PMID- 24745897
TI  - Highly efficient synthesis of ethyl (S)-4-chloro-3-hydroxybutanoate and its
      derivatives by a robust NADH-dependent reductase from E. coli CCZU-K14.
AB  - An NADH-dependent reductase (CmCR) from Candida magnoliae was discovered by
      genome mining for carbonyl reductases. After CmCR was overexpressed in
      Escherichia coli BL21, a robust reductase-producing strain, recombinant E. coli
      CCZU-K14, was employed for the efficient synthesis of ethyl (S)-4-chloro-3
      hydroxybutanoate ((S)-CHBE) from the reduction of ethyl 4-chloro-3-oxobutanoate
      (COBE). After the optimization, the optimum reaction conditions were obtained.
      Notably, E. coli CCZU-K14 had broad substrate specificity in reducing both
      aliphatic and aromatic substrates, and excellent enantioselectivity of CCZU-K14
      was observed for most of the tested substrates, resulting in chiral alcohols of
      over 99.9% ee. Moreover, COBE at a high concentration of (3000mM) could be
      asymmetrically reduced to (S)-CHBE in the high yield (>99.0%) and high
      enantiometric excess value (>99.9% ee) after 14h. Significantly, E. coli CCZU-K14
      shows high potential in the industrial production of (S)-CHBE and its derivatives
      (>99.9% ee). 

PMID- 24745898
TI  - Removal of pharmaceuticals and organic matter from municipal wastewater using two
      stage anaerobic fluidized membrane bioreactor.
AB  - The aim of present study was to treat municipal wastewater in two-stage anaerobic
      fluidized membrane bioreactor (AFMBR) (anaerobic fluidized bed reactor (AFBR)
      followed by AFMBR) using granular activated carbon (GAC) as carrier medium in
      both stages. Approximately 95% COD removal efficiency could be obtained when the
      two-stage AFMBR was operated at total HRT of 5h (2h for AFBR and 3h for AFMBR)
      and influent COD concentration of 250mg/L. About 67% COD and 99% TSS removal
      efficiency could be achieved by the system treating the effluent from primary
      clarifier of municipal wastewater treatment plant, at HRT of 1.28h and OLR of
      5.65kg COD/m(3)d. The system could also effectively remove twenty detected
      pharmaceuticals in raw wastewaters with removal efficiency in the range of 86
      100% except for diclofenac (78%). No other membrane fouling control was required
      except scouring effect of GAC for flux of 16LMH. 

PMID- 24745899
TI  - Feasibilities of consolidated bioprocessing microbes: from pretreatment to
      biofuel production.
AB  - Lignocelluloses are rich sugar treasures, which can be converted to useful
      commodities such as biofuel with the help of efficient combination of enzymes and
      microbes. Although several bioprocessing approaches have been proposed, biofuel
      production from lignocelluloses is limited because of economically infeasible
      technologies for pretreatment, saccharification and fermentation. Use of
      consolidated bioprocessing (CBP) microbes is the most promising method for the
      cost-effective production of biofuels. However, lignocelluloses are obtained from
      highly diverse environment and hence are heterogeneous in nature. Therefore, it
      is necessary to develop and integrate tailor-designed pretreatment processes and
      efficient microbes that can thrive on many different kinds of biomass. In this
      review, the progress towards the construction of consolidated bioprocessing
      microbes, which can efficiently convert heterogeneous lignocellulosic biomass to
      bioenergy, has been discussed; in addition, the potential and constraints of
      current bioprocessing technologies for cellulosic biofuel production have been
      discussed. 

PMID- 24745900
TI  - Biomass production from fermented starch wastewater in photo-bioreactor with
      internal overflow recirculation.
AB  - A photo-bioreactor with internal overflow recirculation was applied to treat real
      fermented starch wastewater and convert it to photosynthetic biomass for further
      utilization. The photo-bioreactor was operated at a hydraulic retention time of
      10days by circulating mixed liquor through overflow pipes and penetrating light
      through infrared transmitting filter. During the operation of 154days, the
      average BOD and COD removals were 95% and 88%, respectively. Majority of
      photosynthetic bacteria was found attached on pipes as biofilm contributed to 82%
      of total biomass production. Photosynthetic biomass yield was 0.51g dried solid/g
      BOD removed and crude protein content of 0.58g/g dried solid. Rhodopseudomonas
      palustris was found in the photosynthetic system as the predominant bacterial
      group by denaturing gradient gel electrophoretic analysis (DGGE) and 16S rDNA
      sequencing method. 

PMID- 24745901
TI  - Occlutech device to salvage aortic rupture.

PMID- 24745902
TI  - Pelvic congestion syndrome: etiology of pain, diagnosis, and clinical management.
AB  - Pelvic congestion syndrome is associated with pelvic varicosities that result in
      chronic pelvic pain, especially in the setting of prolonged standing, coitus,
      menstruation, and pregnancy. Although the underlying pathophysiology of pelvic
      congestion syndrome is unclear, it probably results from a combination of
      dysfunctional venous valves, retrograde blood flow, venous hypertension, and
      dilatation. Asymptomatic women may also have pelvic varicosities, making pelvic
      congestion syndrome difficult to diagnose. This article explores the etiologies
      of pain, use of imaging techniques, and clinical management of pelvic congestion
      syndrome. Possible explanations for the spectrum of pain among women with pelvic
      varicosities are also discussed. 

PMID- 24745903
TI  - Percutaneous sclerotherapy for treatment of tumoral calcinosis.
AB  - Massive tumoral calcinosis developed in a 29-year-old woman with type 1 diabetes
      and failed pancreas and kidney transplant on peritoneal dialysis. The patient had
      a symptomatic calcified, fluid-filled posterior thigh mass. After percutaneous
      drainage of 260 mL of milky fluid, she had rapid recurrence of the collection.
      She underwent catheter-based sclerotherapy first with 110 mL of povidone-iodine
      followed 2 days later by 40 mL of 3% sodium tetradecyl sulfate foam. At 5.5
      months after the procedure, the patient remained asymptomatic, and computed
      tomography imaging showed complete resolution of the collection. 

PMID- 24745904
TI  - Hepatic blood volume imaging with the use of flat-detector CT perfusion in the
      angiography suite: comparison with results of conventional multislice CT
      perfusion.
AB  - PURPOSE: To prospectively determine the feasibility of flat-detector (FD)
      computed tomography (CT) perfusion to measure hepatic blood volume (BV) in the
      angiography suite in patients with hepatocellular carcinoma (HCC). MATERIALS AND
      METHODS: Twenty patients with HCC were investigated with conventional multislice
      and FD CT perfusion. CT perfusion was carried out on a multislice CT scanner, and
      FD CT perfusion was performed on a C-arm angiographic system, before
      transarterial chemoembolization procedures. BV values of conventional and FD CT
      perfusion were measured within tumors and liver parenchyma. The arterial
      perfusion portion of CT perfusion BV was extracted from CT perfusion BV by
      multiplying it by a hepatic perfusion index. Relative values (RVs) for CT
      perfusion arterial BV and FD CT perfusion BV (FD BV) were defined by dividing BV
      of tumor by BV of parenchyma. Relationships between BV and RV values of these two
      techniques were analyzed. RESULTS: In all patients, both perfusion procedures
      were technically successful, and all 33 HCCs larger than 10 mm were identified
      with both imaging methods. There were strong correlations between the absolute
      values of FD BV and CT perfusion arterial BV (tumor, r = 0.903; parenchyma, r =
      0.920; both P < .001). Bland-Altman analysis showed a mean difference of -0.15 +/
      0.24 between RVs for CT perfusion arterial BV and FD BV. CONCLUSIONS: The
      feasibility of FD CT perfusion to assess BV values of liver tumor and surrounding
      parenchyma in the angiographic suite was demonstrated.

PMID- 24745905
TI  - Ablation zones and weight-bearing bones: points of caution for the palliative
      interventionalist.
AB  - PURPOSE: To evaluate and classify underlying mechanisms of adverse outcomes after
      percutaneous computed tomography (CT)-guided cryoablation for palliation of
      painful musculoskeletal metastatic disease. MATERIALS AND METHODS: Data were
      collected for patients who underwent CT-guided percutaneous palliative
      cryoablation for painful musculoskeletal metastatic disease between January 2010
      and December 2012. Cases with adverse outcomes or suboptimal response were
      identified and classified according to the Society of Interventional Radiology
      (SIR) classification system for complications by outcome and according to
      underlying mechanism of the outcome as delineated on follow-up examination.
      RESULTS: There were 61 patients who received ablation for painful musculoskeletal
      metastatic disease. Six patients with adverse outcomes were identified. Two were
      minor complications (A, n = 1; B, n = 1), and four were major complications (C, n
      = 1; D, n = 3). Four patients incurred sequelae related to damage of ancillary
      structures included in the ablation zone, and two patients developed complete
      fractures after ablation of lesions in weight-bearing bones. CONCLUSIONS:
      Complete cryoablation of a painful musculoskeletal metastatic lesion may lead to
      ancillary damage of adjacent structures or fracture in weight-bearing bones.

PMID- 24745906
TI  - Assisted maturation of native fistula in two patients with a continuous flow left
      ventricular assist device.
AB  - Patients who receive a left ventricular assist device (LVAD) are prone to develop
      end-stage renal disease. Primary arteriovenous fistula (AVF) maturation in these
      patients may be unsuccessful secondary to the nonpulsatile flow with an LVAD. Two
      patients with LVADs are described in whom assisted maturation aided long-term AVF
      patency. 

PMID- 24745907
TI  - Technique of percutaneous direct needle puncture of calcified plaque in the
      superficial femoral artery or tibial artery to facilitate balloon catheter
      passage and balloon dilation of calcified lesions.
AB  - Heavy calcified arterial lesions are challenging to endovascular treatment. Even
      if a guide wire passes the lesion, calcified plaque can inhibit passage or
      dilation of the balloon catheter. We developed a novel technique of percutaneous
      direct needle puncture of calcified plaque (PIERCE) to allow subsequent passage
      and dilation of the balloon. PIERCE was performed in three patients with
      superficial femoral artery (SFA) lesions and one patient with a tibial artery
      lesion. In all four cases, balloon passage and lesion dilatation were achieved.
      Minor hemorrhage from the punctured site occurred in two patients with SFA
      lesions, which resolved with stent placement. 

PMID- 24745908
TI  - Electrically conductive catheter inhibits bacterial colonization.
AB  - PURPOSE: To design, prototype, and assess a custom vascular access catheter for
      its ability to inhibit bacterial colonization in vitro and to optimize electric
      parameters for efficacy and safe translation. MATERIALS AND METHODS: A vascular
      access catheter with conductive elements was designed and custom fabricated with
      two electrodes at the tip, separated by a nonconductive segment. The catheter was
      colonized with Staphylococcus aureus and incubated at predetermined current
      levels (4-8 uA) and durations (4-24 h). Catheters were compared using bacterial
      counts and scanning electron microscopy (SEM). RESULTS: Bacteria colony-forming
      units were reduced significantly (P < .05) by > 90% (91.7%-100%) in all
      uninterrupted treatment arms that included electric current (4 uA or 8 uA) of at
      least 8 hours' duration. Qualitative analysis using SEM revealed that the treated
      catheter exposed to electric current had markedly less bacteria compared with the
      untreated catheter. CONCLUSIONS: This catheter with conductive elements inhibits
      bacterial colonization in vitro when very small electric current (4-8 uA) is
      applied across the tip for 8-24 hours. In vivo validation is requisite to future
      translation to the clinical setting.

PMID- 24745909
TI  - Acute iatrogenic pancreatitis complicating CT-guided celiac ganglion neurolysis
      in chronic pancreatitis.

PMID- 24745910
TI  - Testicular artery hemorrhage after inguinal hernia repair.

PMID- 24745911
TI  - Re: "radiofrequency ablation of hepatic cysts: evaluation of therapeutic
      efficacy".

PMID- 24745912
TI  - Reply to: re: "radiofrequency ablation of hepatic cysts: evaluation of
      therapeutic efficacy".

PMID- 24745913
TI  - Infantile hemangioma or kaposiform hemangioendothelioma?

PMID- 24745914
TI  - Modifiable correlates of physical symptoms and health-related quality of life in
      patients with heart failure: a cross-sectional study.
AB  - BACKGROUND: Heart failure is associated with high rates of hospitalization and
      mortality. The majority of patients with heart failure suffer from physical
      symptoms, and these symptoms are strongly associated with poor health-related
      quality of life. To improve physical symptoms and health-related quality of life,
      the modifiable factors associated with physical symptoms need to be examined.
      PURPOSE: To examine modifiable psychosocial and behavioral factors associated
      with physical symptoms and health-related quality of life, and the mediator
      effects of physical symptoms on the relationships between the modifiable factors
      and health-related quality of life in patients with heart failure. METHODS: Data
      on potential correlates of physical symptoms (i.e., depressive symptoms,
      perceived control, social support, medication adherence, sodium intake, and self
      care management) were collected from 109 patients with heart failure (mean age 58
      +/- 14 years, 46% male, 89% New York Heart Association class II/III). Data on
      physical symptoms (Symptom Status Questionnaire-Heart Failure) and health-related
      quality of life (Minnesota Living with Heart Failure) also were collected. Simple
      and multiple regression analyses were used to analyze the data. RESULTS: Among
      the potential correlates, depressive symptoms and sodium intake were associated
      with physical symptoms (F=11.63, p<.001), and depressive symptoms and perceived
      control were associated with health-related quality of life (F=9.917, p<.001).
      Physical symptoms mediated the relationship between depressive symptoms and
      health-related quality of life. CONCLUSION: Improving depressive symptoms and
      eating the appropriate amount of sodium may be primary intervention targets to
      improve physical symptoms. To improve health-related quality of life, depressive
      symptoms as well as physical symptoms need to be managed appropriately.

PMID- 24745915
TI  - Human infection with ORF virus from goats in China, 2012.
AB  - Orf virus, which belongs to the Parapoxvirus genus, induces a zoonotic infectious
      disease characterized by acute, highly vascularized cutaneous pustular lesions in
      sheep and goats. A number of Orf outbreaks have been reported in sheep and goats
      in recent years, but no reports have described an Orf virus strain from humans in
      China. In this study, we diagnosed Orf virus infection in two people, a mother
      and son, in the Gansu province of China. The human Orf virus was isolated and its
      phylogenetic characterization was analyzed based on a complete B2L gene. The
      results are useful for developing prospective programs to control Orf virus
      infections in both goats and humans.

PMID- 24745916
TI  - Socioeconomic disparities in work performance following mild stroke.
AB  - PURPOSE: The purpose of this study was to investigate the relationships among the
      factors that influence return to work for young individuals with mild stroke from
      different socioeconomic backgrounds. METHODS: Prospective cohort study of working
      adults with mild stroke (N = 21). Participants completed an assessment battery of
      cognitive, work environment and work performance measures at approximately 3
      weeks and 7 months post mild stroke. Individuals were placed in "skilled" and
      "unskilled" worker categories based on the Hollingshead Index. RESULTS: Unskilled
      workers had significantly poorer scores on the majority of the cognitive
      assessments. Unskilled workers also perceived less social support (p = 0.017) and
      autonomy (p = 0.049) in work responsibilities than individuals in the skilled
      worker group and also reported significantly poorer work productivity due to
      stroke than those in the skilled group (p = 0.015). CONCLUSIONS: Individuals from
      low socioeconomic backgrounds have more difficulty returning to work following
      mild stroke than individuals from higher socioeconomic backgrounds. Future work
      is needed to identify factors that can increase long-term work success and
      quality of work performance following a mild stroke that specifically targets the
      needs of individuals who have a lower socioeconomic status.

PMID- 24745917
TI  - Construction of standardized surveillance indicators for bovine cysticercosis.
AB  - Bovine cysticercosis is a zoonotic parasitic disease due to Cysticercus bovis.
      This study aimed to identify factors that could have an impact on the prevalence
      of cysticercosis and to use them to build standardized indicators of prevalence.
      Multivariate logistic regression analyses were performed on data from 4,564,065
      cattle (91.3% of the cattle population slaughtered in France in 2010) among which
      6491 cattle (0.14%) were found to harbor at least one lesion of cysticercosis
      (including 611 cattle harboring viable cysts, 0.01%). Two multivariate logistic
      models were fit to the data using as outcome variables either the presence or
      absence of viable cysts and the presence or absence of cysts whatever their level
      of development. Age and sex were identified as the main factors influencing
      bovine cysticercosis prevalence and were used for the construction of
      standardized prevalence and standardized cysticercosis rate. To illustrate the
      use of such indicators, they were calculated for the first and second semester of
      2010 and for two different areas in France. The differences between raw
      prevalence and standardized prevalence highlight the use of standardized
      indicators for comparisons of prevalence between different areas and time periods
      as the structure of the slaughtered populations differ considerably from one to
      another. 

PMID- 24745918
TI  - Editorial: Modifying Cardiovascular Risk Factors: Newer Advances in
      Cardiovascular Metabolism and Diagnostic Technologies.

PMID- 24745919
TI  - Models and Methods in Cardiac Imaging for Metabolism Studies.
AB  - Cardiac health depends on the heart's ability to utilize different substrates to
      support overall oxidative metabolism. To characterize a variety of cardiac
      diseases, there is an ever-growing demand for an accurate non-invasive approach
      to evaluating myocardial substrate metabolism. Data obtained from quantitative
      metabolic imaging modalities add functional information to the anatomic imaging
      modalities and can aid patient management. The goal of this review is to
      emphasize the role of non-invasive imaging techniques (such as PET, SPECT, MR
      spectroscopy and spectroscopic imaging) to detect the metabolic footprints of
      heart disease. The advancements of models and methods to estimate kinetic
      parameters of dynamic processes using data acquired from cardiac imaging
      modalities is discussed. 

PMID- 24745920
TI  - Hyperpolarized Metabolic MR in the Study of Cardiac Function and Disease.
AB  - Several diseases of the heart have been linked to an insufficient ability to
      generate enough energy (ATP) to sustain proper heart function. Hyperpolarized
      magnetic resonance (MR) is a novel technique that can visualize and quantify
      myocardial energy metabolism. Hyperpolarization enhances the MR signal from a
      biological molecule of interest by more than 10,000 times, making it possible to
      measure its cellular uptake and conversion in specific enzymatic pathways in real
      time. We review the role of hyperpolarized MR in identifying changes in cardiac
      metabolism in vivo, and present the extensive literature on hyperpolarized
      pyruvate that has been used to characterize cardiac disease in various in vivo
      models, such as myocardial ischemia, hypertension, diabetes, hyperthyroidism and
      heart failure. The technical aspects of the technique are presented as well as
      the challenges of translating the technique into clinical practice.
      Hyperpolarized MR has the prospect of transforming diagnostic cardiology by
      offering new insights into cardiac disease and potentially even to contribute to
      personalized therapy based on a thorough understanding of the individual
      intracellular metabolism. 

PMID- 24745921
TI  - Cardiological Ultrasound Imaging.
AB  - This review paper is intended for the interested outsider of the field of
      echocardiography and it presents a short introduction into the numerous
      ultrasound (US) methods and techniques for anatomical and functional diagnosis of
      the heart. The basic techniques are generally used for some times already, as
      there are one dimensional (1D) M(otion) mode, the real time 2D B(rightness) mode
      technique and the various Doppler measurement techniques and imaging modes. The M
      mode technique shows the movements of the tissue in a 1D B-mode display vs. time.
      The 2D B-mode images are showing the heart contractions and dilations in real
      time, thus making this technique the basic tool for detecting anatomical
      disturbances and myocardial (localized) abnormal functioning. Improved image
      quality is achieved by Second Harmonic Imaging and myocardial perfusion can be
      quantified using Contrast Agent Imaging. Doppler techniques were introduced in
      the fifties of last century and used for blood flow velocity measurement.
      Continuous wave (CW) Doppler has the advantage of allowing measurement of high
      velocities, as may occur in vascular or valvular stenosis and insufficiency. The
      exact location of the major Doppler signal received cannot be estimated making
      this technique ambiguous in some clinical problems. Single gated Pulse Wave (PW)
      Doppler velocity measurement delivers exact location of the measurement position
      by using an interactively positioned time (=depth) gate in which the velocity is
      being measured. The disadvantage of this technique is the relatively low maximum
      velocity that can be measured. Multigate PW Doppler techniques can be used for
      the assessment of a velocity profile over the vessel cross section. A more
      sophisticated use of this technique is the combination with 2D B-mode imaging in
      the color Doppler mode, called "color flow mapping", in which the multigate
      Doppler signal is color coded and shown in 2D format overlayed in the
      conventional 2D B mode image. In the past two decades, technique to quantify
      myocardial function were developed: Tissue Doppler Imaging (TDI), Strain Rate and
      Strain Imaging. The temporal resolution of ultrasound imaging can be further
      improved by Plane Wave Imaging, and Synthetic Aperture Imaging. The recent
      introduction of 2D matrix transducers extended the real time imaging potential by
      allowing 3D imaging and sophisticated segmentation techniques for the estimation
      of quantitative functional parameters, as for instance cardiac output. 

PMID- 24745922
TI  - Imaging of Organ Metabolism in Obesity and Diabetes: Treatment Perspectives.
AB  - Obesity and diabetes are growing threats for cardiovascular diseases (CVD) and
      heart failure. In order to identify early and effective treatment or prevention
      targets, it is fundamental to dissect the role of each organ and the sequence of
      events leading from health to obesity, diabetes and cardiovascular diseases. The
      advancements in imaging modalities to evaluate organ-specific metabolism in
      humans in vivo is substantially contributing to the stratification of risk,
      identification of organ-specific culprits and development of targeted treatment
      strategies. This review summarizes the contribution provided by imaging of the
      heart, skeletal muscle, adipose tissue, liver, pancreas, gut and brain to the
      understanding of the pathogenesis and cardio-metabolic complications of obesity
      and diabetes, and to the monitoring of treatment responses in humans. We conclude
      by suggesting emerging fields of investigation, including the role of cardiac fat
      in the pathogenesis of cardiovascular disease, the conversion of white into brown
      adipose tissue in the treatment of obesity, the control of weight and energy
      balance by the brain, the integration between omics and imaging technologies to
      help establish biomarkers, and the characterization of gut metabolism in relation
      with the gut microbiome, opening a very promising preventive/therapeutic
      perspective. 

PMID- 24745923
TI  - Psoriasis and Vascular Risk : An Update.
AB  - Psoriasis is a chronic systemic inflammatory disease characterized by topical
      skin lesions as well as an increased risk for cardiovascular disease (CVD). There
      is also increasing evidence that patients with psoriasis are more prone to
      several CVD risk factors (hypertension, obesity, dyslipidemia and smoking), non
      cardiac vascular diseases (carotid, peripheral artery and chronic kidney disease)
      and metabolic co-morbidities (type 2 diabetes mellitus, metabolic syndrome, non
      alcoholic fatty liver disease and obstructive sleep apnea) compared with the
      general population. The associations are even greater in patients with severe
      psoriasis and those with psoriatic arthritis. Insulin resistance, endothelial
      dysfunction and obesity induced by several adipokines and inflammatory cytokines
      are proposed as the common mechanisms linking psoriasis with CVD, vascular risk
      factors and metabolic diseases. The present narrative review considers the
      associations between psoriasis (and psoriatic arthritis) with CVD, vascular risk
      factors and metabolic diseases. Drugs that reduce CVD risk and improve metabolic
      parameters may also beneficially affect psoriasis severity and prognosis.
      Furthermore, anti-psoriatic drugs can exert different effects on CVD risk and
      metabolic co-morbidities. Therefore, physicians should be aware of these
      associations in order to adequately monitor and treat psoriatic patients. 

PMID- 24745924
TI  - Treating Arterial Stiffness in Young and Elderly Patients with the Metabolic
      Syndrome.
AB  - Arterial stiffness is independently associated with increased cardiovascular risk
      in patients with cardiovascular risk factors and in the general population.
      Metabolic syndrome (MetS) is frequently characterized by increased arterial
      stiffness since all components of MetS are implicated in the pathogenesis of
      arterial stiffness. We review the management of arterial stiffness in patients
      with MetS. Several small, short-term studies showed that lifestyle changes,
      antidiabetic, antihypertensive and lipid-lowering agents improve arterial
      elasticity. However, differences appear to exist between different classes of
      agents, with statins and inhibitors of the renin-angiotensin-aldosterone system
      having the more favorable effects on arterial stiffness. A multifactorial
      approach appears to be the optimal management of increased arterial stiffness in
      patients with MetS.

PMID- 24745925
TI  - Hypertension and Atrial Fibrillation: Any Change with the New Anticoagulants.
AB  - Hypertension and atrial fibrillation are the most common cardiovascular risk
      factors and clinically significant arrhythmia, respectively. These conditions
      frequently coexist and their prevalence increases rapidly with aging. Despite
      several different risk factors and clinical conditions predisposing to
      hypertension for its high prevalence in the population is still the main risk
      factor for the development of atrial fibrillation. Several pathophysiologic
      mechanisms (such as structural changes at the level of left ventricle and or
      atrium, neurohormonal activation, arterial stiffness, etc.) can contribute to the
      onset of atrial fibrillation. Some antihypertensive treatments have been shown to
      contribute to reduce the risk of new-onset atrial fibrillation. Atrial
      fibrillation is a major risk factor for stroke, which is further increased in the
      presence of hypertension. For this reason, hypertension is included as a major
      risk factor in the available models for the risk stratification and the
      prevention of thromboembolism in patients with atrial fibrillation. In this
      article we will review the relationship between atrial fibrillation and
      hypertension, looking at the possible specific indications of the antithrombotic
      treatment with new classes of anticoagulants in the prevention of thromboembolic
      events in hypertensive patients with atrial fibrillation. 

PMID- 24745926
TI  - New Insight into Urate-Related Mechanism of Cardiovascular Damage.
AB  - Several experimental and clinical studies reported that hyperuricemia may trigger
      hypertension, metabolic syndrome, vascular damage and renal disease. Furthermore,
      a substantial proportion of epidemiological studies are compatible with the
      hypothesis that hyperuricemia may be an indipendent risk factor for
      cardiovascular disease as well as for an increased cardiovascular mortality.
      Xanthine oxidase is a critical source of reactive oxygen species contributing to
      vascular inflammation and endothelial dysfunction. Although a causal relationship
      between these conditions has not been clearly clarified, the capacity of uric
      acid to negatively affect vascular function by pro-oxidant effects and by
      decreasing nitric oxide bioavailability and consequently induce endothelial
      dysfunction may explain the association among hyperuricemia, hypertension,
      metabolic syndrome, and cardiovascular disease, also by a common mechanicistic
      point of view. 

PMID- 24745927
TI  - Modification of Lifestyle Factors are Needed to Improve the Metabolic Health of
      Patients with Cardiovascular Disease Risk.
AB  - Cardiovascular risk factors, irregardless of their assessment modalities, are
      based on cardiovascular health. Lifestyle influences metabolic profiles and these
      changes affect cardiovascular risk factors. Cardiovascular risk factors can be
      classified into three basic categories: 1. Predisposing risk factors (e.g., age,
      gender, medical history, and genetic factors); 2. Clinical and metabolic factors
      (e.g., hypertension, changes in lipid metabolism, diabetes mellitus, obesity,
      metabolic syndrome, homocysteine, serum uric acid concetntrations, and L-arginine
      dimethylated derivatives); 3. Modifying behavioral factors (e.g., cigarette
      smoking, high caloric diet, alcohol intake, sedentary life). Some of these
      factors are metabolic components of body metabolism because they act by metabolic
      reactions while others characterized by structural alterations of the
      cardiovascular system, at least initially, exert their harmful effects by
      metabolic substrates. Metabolic responses such as biochemical substances, drugs
      or others, that act initially as cardiovascular risk factors, identify that an
      early treatment of the altered parameters observed should be a useful approach to
      reduce the rate of heart attacks with a significant improvement in the outcome of
      cardiovascular disease. 

PMID- 24745928
TI  - Study of complex thermosensitive amphiphilic polyoxazolines and their interaction
      with ionic surfactants. Are hydrophobic, thermosensitive, and hydrophilic
      moieties equally important?
AB  - The temperature-driven self-assembly of nonionic amphiphilic tailor-made triblock
      copolymers has been studied by DLS, NMR, ITC, and SAXS. The composition of these
      triblock copolymers is more complex than that of the vast majority of poly(2
      alkyl-2-oxazoline)s: a statistical thermoresponsive (iPrOx) and hydrophobic
      (BuOx) central block with terminal hydrophilic blocks (MeOx). In general, as
      temperature increases, nanoparticles form in a process starting with single
      molecules that become loose aggregates and ends with the formation of compact
      nanoparticles. Here, we first attempt to resolve the effects of each block on
      nanoparticle formation. It has been proven that the iPrOx/MeOx ratio determines
      the value of the cloud point temperature, whereas the different BuOx-iPrOx blocks
      determine the character of the process. Finally, we complete our investigation by
      presenting the thermodynamic and structural profiles of the complexation between
      these triblock poly(2-alkyl-2-oxazoline)s and two ionic surfactants. The addition
      of an ionic surfactant promotes a rearrangement of the polymer molecules and the
      formation of complexes followed by the appearance of polymer-surfactant hybrid
      micelles. Analysis of the interaction shows a strong and nonspecific reaction
      between the polymers and the anionic surfactant sodium dodecyl sulfate and weak
      but polymer-state-sensitive interactions between the polymer and the cationic
      surfactant hexadecyltrimethylammonium bromide. 

PMID- 24745929
TI  - Characterization of metabolically healthy but obese individuals: should we add
      vitamin D to the puzzle?

PMID- 24745930
TI  - Effect of N-doping of single-walled carbon nanotubes on bioelectrocatalysis of
      laccase.
AB  - Nondoped and N-doped SWCNTs (N-SWCNTs) were used to clarify the effect of N
      doping on a direct electron transfer (DET) reaction of laccase (Lac, from
      Trametes sp.). The level of N-doping in the carbon phase of the N-SWCNTs, which
      were synthesized by a CVD method, was determined to be 0.1, 2.4, and 4.1% from X
      ray photoelectron spectroscopy measurements. The N-SWCNTs were also carefully
      characterized using electron microscopy, Brunauer-Emmett-Teller (BET) specific
      surface area measurements, Raman spectroscopy, and electrochemistry. The
      bioelectrocatalytic current for the DET reaction of Lac immobilized onto the N
      SWCNTs tended to decrease with increasing N dopant ratio, whereas the amount of
      Lac adsorbed per BET surface area of the N-SWCNTs did not depend on the N dopant
      ratio. There were two main explanations for this behavior. First, an
      electrostatic interaction between the positively charged interface of the N
      SWCNTs due to nitrogen species surface functional groups and the negative charges
      of carboxylate residues surrounding the T1 site. Second, the surface potential of
      the N-SWCNTs during Lac modification, because the slope value of the surface
      potential versus N dopant ratio of the N-SWCNTs was about 53 mV/N%. From
      additional investigations into the surface potential effect and thermodynamic
      investigations, we carefully concluded that the above behaviors may be due to
      denaturation and/or decreasing of the DET reaction rate caused by the strong
      electrostatic interaction between Lac and the N-SWCNTs surface. 

PMID- 24745931
TI  - The association between kinematic risky driving among parents and their teenage
      children: moderation by shared personality characteristics.
AB  - This study examined the driving behavior of 42 parent-teenager dyads for 18
      months, under naturalistic driving conditions. At baseline participants'
      personality characteristics were assessed. Objective risky driving measures
      (kinematic risky driving) were captured by accelerometers for the duration of the
      study. To estimate teenage and parent correlations in kinematic risky driving,
      separate Poisson regression models were fit for teenagers and parents.
      Standardized residuals were computed for each trip for each individual.
      Correlations were obtained by estimating the Spearman rank correlations of the
      individual average residuals across teenagers and parents. The bootstrap
      technique was used to estimate the standard errors associated with the parent
      teenager correlations. The overall correlation between teenage and parent
      kinematic risky driving for the 18-month study period was positive, but weak
      (r=0.18). When the association between parent and teenagers' risky driving was
      adjusted for shared personality characteristics, the correlation reduced to 0.09.
      Although interesting, the 95% confidence intervals on the difference between
      these two estimates overlapped zero. We conclude that the weak similarity in
      parent-teen kinematic risky driving was partly explained by shared personality
      characteristics. 

PMID- 24745932
TI  - Valence state driven site preference in the quaternary compound Ca5MgAgGe5: an
      electron-deficient phase with optimized bonding.
AB  - The quaternary phase Ca5Mg0.95Ag1.05(1)Ge5 (3) was synthesized by high
      temperature solid-state techniques, and its crystal structure was determined by
      single-crystal diffraction methods in the orthorhombic space group Pnma-Wyckoff
      sequence c(12) with a = 23.1481(4) A, b = 4.4736(1) A, c = 11.0128(2) A, V =
      1140.43(4) A(3), Z = 4. The crystal structure can be described as linear
      intergrowths of slabs cut from the CaGe (CrB-type) and the CaMGe (TiNiSi-type; M
      = Mg, Ag) structures. Hence, 3 is a hettotype of the hitherto missing n = 3
      member of the structure series with the general formula R(2+n)T2X(2+n),
      previously described with n = 1, 2, and 4. The member with n = 3 was predicted in
      the space group Cmcm-Wyckoff sequence f(5)c(2). The experimental space group Pnma
      (in the nonstandard setting Pmcn) corresponds to a klassengleiche symmetry
      reduction of index two of the predicted space group Cmcm. This transition
      originates from the switching of one Ge and one Ag position in the TiNiSi-related
      slab, a process that triggers an uncoupling of each of the five 8f sites in Cmcm
      into two 4c sites in Pnma. The Mg/Ag site preference was investigated using VASP
      calculations and revealed a remarkable example of an intermetallic compound for
      which the electrostatic valency principle is a critical structure-directing
      force. The compound is deficient by one valence electron according to the Zintl
      concept, but LMTO electronic structure calculations indicate electronic
      stabilization and overall bonding optimization in the polyanionic network. Other
      stability factors beyond the Zintl concept that may account for the electronic
      stabilization are discussed.

PMID- 24745936
TI  - Widespread use of complementary and alternative medicine among non-Hodgkin
      lymphoma survivors.
AB  - There are few studies examining complementary and alternative medicine (CAM) use
      and beliefs among non-Hodgkin lymphoma (NHL) survivors. Seven hundred and
      nineteen patients with NHL from the University of Iowa/Mayo Clinic Molecular
      Epidemiology Resource who completed the 3-year post-diagnosis questionnaire were
      included in this study. Altogether 636 (89%) reported ever using CAM, with 78%
      utilizing vitamins, 54% alternative therapies and 45% herbals. Female gender was
      associated with increased overall CAM use (p=0.0001) as well as use of vitamins
      (p=0.0001), herbals (p=0.006) and alternative therapy (p=0.0002) for cancer.
      Older age (>60) was associated with increased vitamin use (p=0.005) and decreased
      herbal use (p=0.008). Among users, 143 (20%) believed CAM assists healing, 123
      (17%) believed CAM relieves symptoms, 122 (17%) believed CAM gives a feeling of
      control, 110 (15%) believed CAM assists other treatments, 108 (15%) believed CAM
      boosts immunity, 26 (4%) believed CAM cures cancer and 36 (5%) believed CAM
      prevents the spread of cancer.

PMID- 24745937
TI  - Autologous stem cell transplant in recurrent or refractory primary or secondary
      central nervous system lymphoma using thiotepa, busulfan and cyclophosphamide.
AB  - The prognosis for patients with central nervous system (CNS) involvement by
      recurrent or refractory diffuse large B-cell lymphoma is poor, with overall
      survival (OS) of 4-10 months. High-dose chemotherapy (HDC) and autologous stem
      cell transplant (ASCT) is a potential treatment alternative. We reviewed patients
      with recurrent primary (PCNSL) or secondary (SCNSL) CNS lymphoma referred for
      consolidation HDC-ASCT utilizing thiotepa, busulfan and cyclophosphamide (TBC).
      Among the 17 patients included, all had achieved a complete remission after
      salvage induction chemotherapy, which incorporated methotrexate in 82% of
      patients. Two patients failed stem-cell harvesting and 15 (88%) underwent
      transplant. The estimated 3-year progression-free survival (PFS) and OS were both
      93% (95% confidence interval 61-99%). Median PFS and OS were not reached. There
      was no transplant-related mortality. These results confirm the benefit of TBC
      followed by ASCT in select patients with recurrent PCNSL and suggest a potential
      role for the regimen in those with SCNSL. Further investigation is warranted.

PMID- 24745938
TI  - To the end of chronic lymphocytic leukemia: what should be the role of allogeneic
      transplant?

PMID- 24745939
TI  - Discussion.

PMID- 24745940
TI  - Anatomic characteristics and natural history of renal artery aneurysms during
      longitudinal imaging surveillance.
AB  - OBJECTIVE: Renal artery aneurysms (RAAs) are uncommon, and rates of growth and
      rupture are unknown. Limited evidence therefore exists to guide clinical
      management of RAAs, particularly small aneurysms that are asymptomatic. To
      further characterize the natural history of RAAs, we studied anatomic
      characteristics and changes in diameter during imaging surveillance. METHODS:
      Patients evaluated for native RAAs at a single institution during a 5-year period
      (July 2008 to July 2013) were identified and analyzed retrospectively. Patients
      with two or more cross-sectional imaging studies (computed tomography or magnetic
      resonance imaging) more than 1 month apart were included. Demographic and
      clinical data were collected from medical records, and anatomic data (including
      aneurysm diameter, calcification, and location) were obtained from electronic
      images. Changes in RAA diameters over time were evaluated by plots and Wilcoxon
      signed rank tests. RESULTS: Sixty-eight RAAs in 55 patients were analyzed. Median
      follow-up was 19.4 months (interquartile range, 11.2-49.0 months). Mean age at
      presentation was 61.8 +/- 9.8 years, and 73% of patients were women. Hypertension
      was prevalent among 73% of patients. Multiple RAAs were present in 18% of
      patients, and 24% also had arterial aneurysms of other splanchnic or iliac
      vessels. The majority of RAAs were calcified and located at the main renal artery
      bifurcation. Mean initial aneurysm diameter was 16.0 +/- 6.4 mm. Median
      annualized growth rate was 0.06 mm (interquartile range, -0.07 to 0.33 mm; P =
      .11). No RAA ruptures or acute symptoms occurred during surveillance, and 10.3%
      of RAAs were repaired electively. CONCLUSIONS: Risk of short-term RAA growth or
      rupture was low. These findings suggest that annual (or less frequent) imaging
      surveillance is safe in the majority of patients and do not support pre-emptive
      repair of asymptomatic, small-diameter RAAs.

PMID- 24745941
TI  - Evaluation of remodeling process in small-diameter cell-free tissue-engineered
      arterial graft.
AB  - OBJECTIVE: Autologous grafts are used to repair atherosclerotic cardiovascular
      diseases; however, many patients lack suitable donor graft tissue. Recently,
      tissue engineering techniques have emerged to make biologically active blood
      vessels. We applied this technique to produce arterial grafts using established
      biodegradable materials without cell seeding. The grafts were evaluated in vivo
      for vessel remodeling during 12 months. METHODS: Poly(L-lactide-co-epsilon
      caprolactone) scaffolds reinforced by poly(lactic acid) (PLA) fiber were prepared
      as arterial grafts. Twenty-eight cell-free grafts were implanted as infrarenal
      aortic interposition grafts in 8-week-old female SCID/Bg mice. Serial ultrasound
      and micro computed tomography angiography were used to monitor grafts after
      implantation. Five grafts were harvested for histologic assessments and reverse
      transcription-quantitative polymerase chain reaction analysis at time points
      ranging from 4 months to 1 year after implantation. RESULTS: Micro computed
      tomography indicated that most implanted mice displayed aneurysmal changes (three
      of five mice at 4 months, four of five mice at 8 months, and two of five mice at
      12 months). Histologic assessments demonstrated extensive tissue remodeling
      leading to the development of well-circumscribed neovessels with an endothelial
      inner lining, a neointima containing smooth muscle cells and elastin, and a
      collagen-rich extracellular matrix. There were a few observed calcified deposits,
      located around residual PLA fibers at 12 months after implantation. Macrophage
      infiltration into the scaffold, as evaluated by F4/80 immunohistochemical
      staining, remained after 12 months and was focused mostly around residual PLA
      fibers. Reverse transcription-quantitative polymerase chain reaction analysis
      revealed that gene expression of Itgam, a marker for macrophages, and of matrix
      metalloproteinase 9 was higher than in native aorta during the course of 12
      months, indicating prolonged inflammation (Itgam at 8 months: 11.75 +/- 0.99 vs
      native aorta, P < .01; matrix metalloproteinase 9 at 4 months: 4.35 +/- 3.05 vs
      native aorta, P < .05). CONCLUSIONS: In this study, we demonstrated well
      organized neotissue of cell-free biodegradable arterial grafts. Although most
      grafts experienced aneurysmal change, such findings provide insight into the
      process of tissue-engineered vascular graft remodeling and should allow informed
      rational design of the next generation of arterial grafts.

PMID- 24745942
TI  - In vitro efficacy of antibiotic beads in treating abdominal vascular graft
      infections.
AB  - OBJECTIVE: Abdominal aortic vascular graft infection often involves several
      different organisms. Antibiotic polymethyl methacrylate (PMMA) beads may be
      effective in controlling infection after debridement, but bacterial species
      identification and antibiotic susceptibility are often not available at the time
      of operation, generating a need for a broad-spectrum drug combination for
      empirical use. We sought to determine an effective antibiotic in PMMA beads for
      use in abdominal vascular graft infection. METHODS: PMMA beads were impregnated
      with combinations of antibiotics, consisting of daptomycin, tobramycin, and
      meropenem. Antibiotics were selected on the basis of activity spectrum and heat
      stability. Beads were placed on separate agar plates with vancomycin-resistant
      Enterococcus faecalis, Klebsiella pneumoniae, Staphylococcus epidermidis, and
      methicillin-resistant Staphylococcus aureus. Antibiotic inhibition was recorded
      by use of a modified agar-based disk-diffusion method. RESULTS: Daptomycin alone
      was not active against K. pneumoniae (average = 0 mm). Tobramycin alone was not
      active against vancomycin-resistant E. faecalis, K. pneumoniae, or methicillin
      resistant S. aureus. Tobramycin and daptomycin in combination had moderate broad
      spectrum activity with 8- to 14-mm mean inhibition halos. Meropenem showed strong
      activity against all tested organisms with >15-mm mean inhibition halos. The
      addition of daptomycin to meropenem provided improved coverage of gram-positive
      organisms. The presence of tobramycin reduced the efficacy of meropenem.
      CONCLUSIONS: Antibiotic PMMA beads containing 10% meropenem with 2.5% daptomycin
      had excellent in vitro activity against typical bacterial species associated with
      abdominal vascular graft infections. The addition of antibiotic beads may be a
      useful adjunct in managing such cases. Further studies are required to determine
      efficacy in clinical practice.

PMID- 24745943
TI  - Lymphovenous anastomosis for recurrent swelling syndrome and chylous effusion due
      to cervical thoracic duct cyst.
AB  - Thoracic duct (TD) cyst is an uncommon abnormality that can be manifested as a
      cervical swelling. Pathogenesis includes congenital or degenerative weakness of
      the wall of the TD and obstruction of the lymphoid flow. Diagnosis is crucial to
      eliminate malignant disease or vein thrombosis and can be established by imaging
      and needle aspiration. We report a case of recurrent cervical swelling with
      spontaneous chylothorax and chyloperitoneum. A TD cyst with a terminal
      obstruction of the TD was diagnosed on lymphangiography. Treatment by
      microsurgical lymphovenous anastomosis was successful, and the patient was free
      of symptom 3 years later.

PMID- 24745944
TI  - The feasibility of cone beam computed tomographic sialography in the diagnosis of
      space-occupying lesions: report of 3 cases.
AB  - Cone beam computed tomography (CBCT) is being widely used in recent years and has
      modernized the practice of oral and maxillofacial radiology by its inherent
      advantages, such as short scanning time, high resolution, and low dose of
      radiation to the patient. Sialography can be considered as the second step of
      assessment of space-occupying masses after initial diagnosis with
      ultrasonography. Sialography is combined with plain radiographs in routine
      practice. It can also be combined with advanced modalities such as computed
      tomography (CT), magnetic resonance imaging (MRI), and CBCT. In this report, we
      describe 3 cases to confirm the feasibility and superiority of sialography using
      CBCT and 3-dimensional (3D) images in space-occupying lesions of major salivary
      glands when conventional sialography is not diagnostic or MRI and CT are not
      easily available or affordable. CBCT sialography and its 3D images can be helpful
      in the diagnosis of space-occupying lesions of major salivary glands.

PMID- 24745945
TI  - Identification and validation of novel PERK inhibitors.
AB  - PERK, as one of the principle unfolded protein response signal transducers, is
      believed to be associated with many human diseases, such as cancer and type-II
      diabetes. There has been increasing effort to discover potent PERK inhibitors due
      to its potential therapeutic interest. In this study, a computer-based virtual
      screening approach is employed to discover novel PERK inhibitors, followed by
      experimental validation. Using a focused library, we show that a consensus
      approach, combining pharmacophore modeling and docking, can be more cost
      effective than using either approach alone. It is also demonstrated that the
      conformational flexibility near the active site is an important consideration in
      structure-based docking and can be addressed by using molecular dynamics. The
      consensus approach has further been applied to screen the ZINC lead-like
      database, resulting in the identification of 10 active compounds, two of which
      show IC50 values that are less than 10 MUM in a dose-response assay. 

PMID- 24745946
TI  - Here/In this issue and there/Abstract thinking: Disruptive mood dysregulation
      disorder and severe mood dysregulation.

PMID- 24745947
TI  - Helping troubled children: divergent discourses.

PMID- 24745948
TI  - Sunsetting DSM-IV's pervasive developmental disorder.

PMID- 24745949
TI  - Risk for mood pathology: neural and psychological markers of abnormal negative
      information processing.

PMID- 24745950
TI  - A comparison of DSM-IV pervasive developmental disorder and DSM-5 autism spectrum
      disorder prevalence in an epidemiologic sample.
AB  - OBJECTIVE: Changes in autism diagnostic criteria found in DSM-5 may affect autism
      spectrum disorder (ASD) prevalence, research findings, diagnostic processes, and
      eligibility for clinical and other services. Using our published, total
      population Korean prevalence data, we compute DSM-5 ASD and social communication
      disorder (SCD) prevalence and compare them with DSM-IV pervasive developmental
      disorder (PDD) prevalence estimates. We also describe individuals previously
      diagnosed with DSM-IV PDD when diagnoses change with DSM-5 criteria. METHOD: The
      target population was all children from 7 to 12 years of age in a South Korean
      community (N = 55,266), those in regular and special education schools, and a
      disability registry. We used the Autism Spectrum Screening Questionnaire for
      systematic, multi-informant screening. Parents of screen-positive children were
      offered comprehensive assessments using standardized diagnostic procedures,
      including the Autism Diagnostic Interview-Revised and Autism Diagnostic
      Observation Schedule. Best-estimate clinical diagnoses were made using DSM-IV PDD
      and DSM-5 ASD and SCD criteria. RESULTS: DSM-5 ASD estimated prevalence was 2.20%
      (95% confidence interval = 1.77-3.64). Combined DSM-5 ASD and SCD prevalence was
      virtually the same as DSM-IV PDD prevalence (2.64%). Most children with autistic
      disorder (99%), Asperger disorder (92%), and PDD-NOS (63%) met DSM-5 ASD
      criteria, whereas 1%, 8%, and 32%, respectively, met SCD criteria. All remaining
      children (2%) had other psychopathology, principally attention
      deficit/hyperactivity disorder and anxiety disorder. CONCLUSION: Our findings
      suggest that most individuals with a prior DSM-IV PDD meet DSM-5 diagnostic
      criteria for ASD and SCD. PDD, ASD or SCD; extant diagnostic criteria identify a
      large, clinically meaningful group of individuals and families who require
      evidence-based services.

PMID- 24745951
TI  - Parental suicide attempt and offspring self-harm and suicidal thoughts: Results
      from the Avon Longitudinal Study of Parents and Children (ALSPAC) birth cohort.
AB  - OBJECTIVE: Parental suicidal behavior is associated with offspring's risk of
      suicidal behavior. However, much of the available evidence is from population
      registers or clinical samples. We investigated the associations of self-reported
      parental suicide attempt (SA) with offspring self-harm and suicidal thoughts in
      the Avon Longitudinal Study of Parents and Children (ALSPAC), a prospective birth
      cohort. METHOD: Parental SA was self-reported on 10 occasions from pregnancy
      until their child was 11 years of age. Offspring self-reported lifetime self
      harm, with and without suicidal intent, suicidal thoughts, and suicide plans, at
      age 16 to 17 years. Multivariable regression models quantified the association
      between parental SA and offspring outcomes controlling for confounders. RESULTS:
      Data were available for 4,396 mother-child and 2,541 father-child pairs.
      Adjusting for confounders including parental depression, maternal SA was
      associated with a 3-fold increased risk of self-harm with suicidal intent in
      their children (adjusted odds ratio [aOR] = 2.94, 95% confidence interval [CI] =
      1.43-6.07) but not with self-harm without suicidal intent (aOR = 0.83, 95% CI =
      0.35-1.99). Children whose mother attempted suicide were more likely to report
      suicidal thoughts and plans (aOR = 5.04, 95% CI = 2.24-11.36; aOR = 2.17, 95% CI
      = 1.07-4.38, respectively). Findings in relation to paternal SA were somewhat
      weaker and not significant. CONCLUSIONS: Maternal SA increased their offspring's
      risk of self-harm with suicidal intent and of suicidal thoughts, but was
      unrelated to self-harm without intent; findings for paternal suicide attempt were
      weaker and not significant. Maternal SA, which may not come to the attention of
      health care professionals, represents a major risk for psychiatric morbidity in
      their offspring.

PMID- 24745952
TI  - School mobility and prospective pathways to psychotic-like symptoms in early
      adolescence: a prospective birth cohort study.
AB  - OBJECTIVE: Social adversity and urban upbringing increase the risk of psychosis.
      We tested the hypothesis that these risks may be partly attributable to school
      mobility and examined the potential pathways linking school mobility to psychotic
      like symptoms. METHOD: A community sample of 6,448 mothers and their children
      born between 1991 and 1992 were assessed for psychosocial adversities (i.e.,
      ethnicity, urbanicity, family adversity) from birth to 2 years, school and
      residential mobility up to 9 years, and peer difficulties (i.e., bullying
      involvement and friendship difficulties) at 10 years. Psychotic-like symptoms
      were assessed at age 12 years using the Psychosis-like Symptoms Interview
      (PLIKSi). RESULTS: In regression analyses, school mobility was significantly
      associated with definite psychotic-like symptoms (odds ratio [OR] =1.60; 95% CI
      =1.07-2.38) after controlling for all confounders. Within path analyses, school
      mobility (probit coefficient [beta] = 0.108; p = .039), involvement in bullying
      (beta = 0.241; p < .001), urbanicity (beta = 0.342; p = .016), and family
      adversity (beta = 0.034; p < .001) were all independently associated with
      definite psychotic-like symptoms. School mobility was indirectly associated with
      definite psychotic-like symptoms via involvement in bullying (beta = 0.018; p =
      .034). CONCLUSIONS: School mobility is associated with increased risk of
      psychotic-like symptoms, both directly and indirectly. The findings highlight the
      potential benefit of strategies to help mobile students to establish themselves
      within new school environments to reduce peer difficulties and to diminish the
      risk of psychotic-like symptoms. Awareness of mobile students as a possible high
      risk population, and routine inquiry regarding school changes and bullying
      experiences, may be advisable in mental health care settings.

PMID- 24745953
TI  - An empirically derived classification of adolescent personality disorders.
AB  - OBJECTIVE: This study describes an empirically derived approach to diagnosing
      adolescent personality pathology that is clinically relevant and empirically
      grounded. METHOD: A random national sample of psychiatrists and clinical
      psychologists (N = 950) described a randomly selected adolescent patient (aged 13
      18 years, stratified by age and gender) in their care using the Shedler-Westen
      Assessment Procedure-II-A for Adolescents (SWAP-II-A) and several additional
      questionnaires. RESULTS: We applied a form of factor analysis to identify
      naturally occurring personality groupings within the patient sample. The analysis
      yielded 10 clinically coherent adolescent personality descriptions organized into
      3 higher-order clusters (internalizing, externalizing, and borderline
      dysregulated). We also obtained a higher-order personality strengths factor.
      These factors and clusters strongly resembled but were not identical to factors
      similarly identified in adult patients. In a second, independent sample from an
      intensive day treatment facility, 2 clinicians (the patients' treating clinician
      and the medical director) independently completed the SWAP-II-A, the Child
      Behavior Checklist (CBCL), and a measure of adaptive functioning. Two additional
      clinicians, blinded to the data from the first 2 clinicians, independently rated
      patients' ward behavior using a validated measure of interpersonal behavior.
      Clinicians diagnosed the personality syndromes with high agreement and minimal
      comorbidity among diagnoses, and SWAP-II-A descriptions strongly correlated in
      expected ways with the CBCL, adaptive functioning, and ward ratings. CONCLUSION:
      The results support the importance of personality diagnosis in adolescents and
      provide an approach to diagnosing adolescent personality that is empirically
      based and clinically useful.

PMID- 24745954
TI  - Sleep problems predict and are predicted by generalized anxiety/depression and
      oppositional defiant disorder.
AB  - OBJECTIVE: We tested whether sleep problems co-occur with, precede, and/or follow
      common psychiatric disorders during childhood and adolescence. We also clarified
      the role of comorbidity and tested for specificity of associations among sleep
      problems and psychiatric disorders. METHOD: Data came from the Great Smoky
      Mountains Study, a representative population sample of 1,420 children, assessed 4
      to 7 times per person between ages 9 and 16 years for major Diagnostic and
      Statistical Manual-Fourth Edition (DSM-IV) disorders and sleep problems. Sleep
      related symptoms were removed from diagnostic criteria when applicable. RESULTS:
      Sleep problems during childhood and adolescence were common, with restless sleep
      and difficulty falling asleep being the most common symptoms. Cross-sectional
      analyses showed that sleep problems co-occurred with many psychiatric disorders.
      Longitudinal analyses revealed that sleep problems predicted increases in the
      prevalence of later generalized anxiety disorder (GAD) and high GAD/depression
      symptoms, and oppositional defiant disorder (ODD). In turn, GAD and/or depression
      and ODD predicted increases in sleep problems over time. CONCLUSIONS: Sleep
      problems both predict and are predicted by a diagnostic cluster that includes
      ODD, GAD, and depression. Screening children for sleep problems could offer
      promising opportunities for reducing the burden of mental illness during the
      early life course.

PMID- 24745955
TI  - Amygdala-function perturbations in healthy mid-adolescents with familial
      liability for depression.
AB  - OBJECTIVE: Functional magnetic resonance imaging (fMRI) studies have identified
      increased amygdala responses to negative stimuli as a risk marker of depression
      in adults, and as a state marker of depression in adults and adolescents.
      Hyperreactivity of the amygdala has been linked to negatively biased emotional
      processing in depression. However, no study has elucidated whether similar
      amygdala perturbations can be found in healthy mid-adolescents with familial
      liability for depression. We hypothesized that healthy 14-year-olds with
      relatives with depression would demonstrate increased amygdala responses to
      negative stimuli, as compared with their peers with no family history of mental
      disorders. METHOD: We investigated a community-based sample of 164 typically
      developing 14-year-olds without record of past or current mental disorders. Of
      these individuals, 28 fulfilled criteria for family history of depression, and
      136 served as controls. Groups did not differ with regard to cognitive ability,
      depressive symptomatology, and anxiety. During fMRI they performed a perceptual
      discrimination task in which visual target and distractor stimuli varied
      systematically with regard to emotional valence. RESULTS: Both a hypothesis
      driven region-of-interest analysis and a whole-brain analysis of variance
      revealed that negative distractors elicited greater amygdala activation in
      adolescents with a family history of depression compared to controls. Amygdala
      responses also differed during the processing of negative target stimuli, but
      effects were reversed. CONCLUSION: Our study demonstrates that familial liability
      for depression is associated with correlates of negatively biased emotional
      processing in healthy adolescents. Amygdala perturbations during the processing
      of negative stimuli might reflect an early and subtle risk marker for depression.

PMID- 24745956
TI  - Predictive neurofunctional markers of attention-deficit/hyperactivity disorder
      based on pattern classification of temporal processing.
AB  - OBJECTIVE: Attention-deficit/hyperactivity disorder (ADHD) is currently diagnosed
      on the basis of subjective measures, despite evidence for multi-systemic
      structural and neurofunctional deficits. A consistently observed neurofunctional
      deficit is in fine-temporal discrimination (TD). The aim of this proof-of-concept
      study was to examine the feasibility of distinguishing patients with ADHD from
      controls using multivariate pattern recognition analyses of functional magnetic
      resonance imaging (fMRI) data of TD. METHOD: A total of 20 medication-naive
      adolescent male patients with ADHD and 20 age-matched healthy controls underwent
      fMRI while performing a TD task. The fMRI data were analyzed with Gaussian
      process classifiers to predict individual ADHD diagnosis based on brain
      activation patterns. RESULTS: The pattern of brain activation correctly
      classified up to 80% of patients and 70% of controls, achieving an overall
      classification accuracy of 75%. The distributed activation networks with the
      highest delineation between patients and controls corresponded to a distributed
      network of brain regions involved in TD and typically compromised in ADHD,
      including inferior and dorsolateral prefrontal, insula, and parietal cortices,
      and the basal ganglia, anterior cingulate, and cerebellum. These regions
      overlapped with areas of reduced activation in patients with ADHD relative to
      controls in a univariate analysis, suggesting that these are dysfunctional
      regions. CONCLUSIONS: We show evidence that pattern recognition analyses combined
      with fMRI using a disorder-sensitive task such as timing have potential in
      providing objective diagnostic neuroimaging biomarkers of ADHD.

PMID- 24745957
TI  - Disrupted expected value signaling in youth with disruptive behavior disorders to
      environmental reinforcers.
AB  - OBJECTIVE: Youth with disruptive behavior disorders (DBD), including conduct
      disorder (CD) and oppositional defiant disorder (ODD), have difficulties in
      reinforcement-based decision making, the neural basis of which is poorly
      understood. Studies examining decision making in youth with DBD have revealed
      reduced reward responses within the ventromedial prefrontal cortex/orbitofrontal
      cortex (vmPFC/OFC), increased responses to unexpected punishment within the vmPFC
      and striatum, and reduced use of expected value information in the anterior
      insula cortex and dorsal anterior cingulate cortex during the avoidance of
      suboptimal choices. Previous work has used only monetary reinforcement. The
      current study examined whether dysfunction in youth with DBD during decision
      making extended to environmental reinforcers. METHOD: A total of 30 youth (15
      healthy youth and 15 youth with DBD) completed a novel reinforcement-learning
      paradigm using environmental reinforcers (physical threat images, e.g., striking
      snake image; contamination threat images, e.g., rotting food; appetitive images,
      e.g., puppies) while undergoing functional magnetic resonance imaging (fMRI).
      RESULTS: Behaviorally, healthy youth were significantly more likely to avoid
      physical threat, but not contamination threat, stimuli than youth with DBD.
      Imaging results revealed that youth with DBD showed significantly reduced use of
      expected value information in the bilateral caudate, thalamus, and posterior
      cingulate cortex during the avoidance of suboptimal responses. CONCLUSIONS: The
      current data suggest that youth with DBD show deficits to environmental
      reinforcers similar to the deficits seen to monetary reinforcers. Importantly,
      this deficit was unrelated to callous-unemotional (CU) traits, suggesting that
      caudate impairment may be a common deficit across youth with DBD.

PMID- 24745959
TI  - Low-flow mediated constriction: the yin to FMD's yang?
AB  - Given the prevalence of cardiovascular disease (CVD), early detection is crucial.
      Although traditional cardiovascular risk factors relate to future CVD, the
      predictive value of these risk factors can be relatively limited. Contemporary
      scientific attention has focused on alternative direct measures of arterial
      function. Based on the ability of the endothelium to acutely dilate in response
      to an increase in flow, 'flow mediated dilation' (FMD) was introduced
      approximately 20 years ago and is now an established non-invasive index of
      endothelial function predictive of future cardiovascular events. Recently, 'low
      flow mediated constriction' (L-FMC) has been proposed as a complementary addition
      to FMD. The technique is based on the constrictor response to decreased flow and
      is claimed to improve the sensitivity and specificity of FMD. The aim of this
      review is to examine literature pertaining to this novel technique and to provide
      insight into the potential use of L-FMC in future research. 

PMID- 24745960
TI  - A high school wrestler with severe bradycardia.

PMID- 24745961
TI  - Three-dimensional computed tomographic findings of bridging bronchus with
      pulmonary artery compression.

PMID- 24745962
TI  - Resonant tunneling through discrete quantum states in stacked atomic-layered
      MoS2.
AB  - Two-dimensional crystals can be assembled into three-dimensional stacks with
      atomic layer precision, which have already shown plenty of fascinating physical
      phenomena and been used for prototype vertical-field-effect-transistors.1,2 In
      this work, interlayer electron tunneling in stacked high-quality crystalline MoS2
      films were investigated. A trilayered MoS2 film was sandwiched between top and
      bottom electrodes with an adjacent bottom gate, and the discrete energy levels in
      each layer could be tuned by bias and gate voltages. When the discrete energy
      levels aligned, a resonant tunneling peak appeared in the current-voltage
      characteristics. The peak position shifts linearly with perpendicular magnetic
      field, indicating formation of Landau levels. From this linear dependence, the
      effective mass and Fermi velocity are determined and are confirmed by electronic
      structure calculations. These fundamental parameters are useful for exploitation
      of its unique properties. 

PMID- 24745963
TI  - Synthesis of beta-allylbutenolides via one-pot copper-catalyzed
      hydroallylation/cyclization of gamma-hydroxybutynoate derivatives.
AB  - One-pot copper-catalyzed hydroallylation/lactone cyclization of gamma
      hydroxybutynoate derivatives was developed to afford beta-allylbutenolides. 

PMID- 24745964
TI  - Design, synthesis, docking and anti-inflammatory evaluation of novel series of
      benzofuran based prodrugs.
AB  - Several new benzofuran derivatives were synthesized, via appropriate synthetic
      route as anti-inflammatory agents. The anti-inflammatory activity of the prepared
      compounds was evaluated using carrageenan rat model. Among the synthesized
      compounds, some compounds showed comparable anti-inflammatory activity to
      nimesulide, the standard drug taken for anti-inflammatory studies. Docking study
      of the prepared compounds was performed for the study of interaction of molecules
      with the active site of COX-2. Preliminary biological studies and docking gave an
      interesting insight, into the validity of employing benzofuran analogues as good
      anti-inflammatory agent. 

PMID- 24745965
TI  - Towards the discovery of drug-like epigallocatechin gallate analogs as Hsp90
      inhibitors.
AB  - (-)-Epigallocatechin gallate (EGCG) is the major flavonoid of green tea and has
      been widely explored for a range of biological activities including anti
      infective, anti-inflammatory, anti-cancer, and neuroprotection. Existing
      structure-activity data for EGCG has been largely limited to exploration of
      simple ethers and hydroxyl deletion. EGCG has poor drug-like properties because
      of multiple phenolic hydroxyl moieties and a metabolically labile ester. This
      work reports a substantial expansion of structure-activity understanding by
      exploring a range of semi-synthetic and synthetic derivatives with ester
      replacements and variously substituted aromatic and alicyclic groups containing
      more drug-like substituents. Structure-activity relationships for these molecules
      were obtained for Hsp90 inhibition. The results indicate that amide and
      sulfonamide linkers are suitable ester replacements. Hydroxylated aromatic rings
      and the cis-stereochemistry in EGCG are not essential for Hsp90 inhibition.
      Selected analogs in this series are more potent than EGCG in a luciferase
      refolding assay for Hsp90 activity. 

PMID- 24745966
TI  - Improvement of a streptavidin-binding aptamer by LNA- and alpha-l-LNA
      substitutions.
AB  - Forty modified versions of a streptavidin-binding aptamer each containing single
      or multiple LNA or alpha-l-LNA-substitutions were synthesized and their
      dissociation constants determined by surface plasmon resonance experiments. Both
      full-length and truncated versions of the aptamer were studied and compared with
      the unmodified DNA aptamers. A ~two-fold improvement in binding affinity was
      achieved by incorporation of LNA nucleotides in the 3'-part of the stems of the
      streptavidin-binding aptamer whereas LNA- and alpha-l-LNA-substitutions in the
      terminal stem increased the serum stability. 

PMID- 24745967
TI  - Benzylpiperidine variations on histamine H3 receptor ligands for improved drug
      likeness.
AB  - Several hH3R antagonists/inverse agonists entered clinical phases for a broad
      spectrum of mainly centrally occurring diseases. Nevertheless, many promising
      candidates failed due to their pharmacokinetic profile, mostly because of their
      strong lipophilicity and their dibasic character. Analysis of previously, as
      potential PET ligands synthesized compounds (ST-889, ST-928) revealed promising
      results concerning physicochemical properties and drug-likeness. Herein, the
      synthesis, the evaluation of the binding properties at the hH3R and the
      estimation of different physicochemical and drug-likeness properties of further
      novel benzylpiperidine variations on H3R antagonists is described. Due to the
      introduction of various small hydrophilic moieties in the structure, drug
      likeness parameters have been improved. For instance, compound 12 (ST-1032)
      showed in addition to high affinity at the H3R (pKi (hH3R)=9.3) clogS, clogP, LE,
      LipE, and LELP values of -2.48, 2.18, 0.44, 7.14, and 4.95, respectively. Also,
      the keto derivative 5 (ST-1703, pKi (hH3R)=8.6) revealed LipE and LELP values of
      5.25 and 6.84, respectively. 

PMID- 24745968
TI  - Synthesis of new simplified hemiasterlin derivatives with alpha,beta-unsaturated
      carbonyl moiety.
AB  - In this Letter, we report a convenient and efficient method for the synthesis of
      new simplified derivatives of hemiasterlin in which the alpha,alpha
      dimethylbenzylic moiety A is replaced by alpha,beta-unsaturated aryl groups as
      Michael acceptor. Most of these derivatives have a strong cytotoxic activity on
      three human tumor cell lines (KB, Hep-G2 and MCF7). Analogs 17b and 17f showed a
      high cytotoxicity against KB and Hep-G2 cancer cell lines comparable to
      paclitaxel and ellipticine. 

PMID- 24745969
TI  - Identification of the first potent, selective and bioavailable PPARalpha
      antagonist.
AB  - The discovery and SAR of a novel series of potent and selective PPARalpha
      antagonists are herein described. Exploration of replacements for the labile acyl
      sulfonamide linker led to a biaryl sulfonamide series of which compound 33 proved
      to be suitable for further profiling in vivo. Compound 33 demonstrated excellent
      potency, selectivity against other nuclear hormone receptors, and good
      pharmacokinetics in mouse. 

PMID- 24745970
TI  - Synthesis and anti-BVDV activity of novel delta-sultones in vitro: implications
      for HCV therapies.
AB  - In this study we report the synthesis and activity against bovine viral diarrhea
      virus (BVDV) of a novel series of bicycle delta-sultones containing gamma
      lactones. BVDV is responsible for major losses in cattle. Some of the synthesized
      delta-sultones showed pronounced anti-BVDV activity with EC50 values of 0.12
      1.0MUM and no significant cytotoxicity. Among them, the ortho bromosubstituted
      derivative 4f (EC50=0.12MUM) showed better antiviral activity than other
      derivatives and was 10 fold more that of than positive control ribavirin
      (EC50=1.3MUM). BVDV is also considered to be a valuable surrogate for the
      hepatitis C virus (HCV) in antiviral drug studies. The above results provided a
      novel candidate for the development of anti-HCV agents. 

PMID- 24745971
TI  - Tahyna virus infection, a neglected arboviral disease in the Qinghai-Tibet
      Plateau of China.
AB  - Tahyna virus (TAHV) was first isolated from mosquitoes collected in the suburbs
      of Geermu city in the Qinghai-Tibet Plateau of China in 2007. Since then, TAHV
      antibodies have been detected in local livestock in Geermu, Qinghai. To determine
      whether the disease caused by TAHV was present in local residents, an
      investigation was conducted in the summer of 2009. During this investigation,
      ward inspections were conducted in rural clinics, and clinical information and
      specimens were collected from patients who complained mainly of acute fever. The
      collected samples were tested by serological and molecular methods. The results
      showed that four samples were positive for TAHV immunoglobulin M and had four
      fold or higher levels of TAHV-neutralizing antibody titers between convalescent
      phase and acute-phase, and that TAHV nucleotide sequences were detected in two
      acute sera. Clinical features of TAHV infection commonly included fever,
      accounting for 100%. Among all other symptoms, the one with the highest frequency
      was pharyngitis (80%), followed by malaise, inappetence, arthralgia, headache,
      and drowsiness. Follow-up surveys revealed that all cases recovered in 2-5 days
      after onset, and no serious or deadly cases were observed. This is the first time
      that the disease caused by TAHV infection has been reported in China. TAHV
      infection is another known mosquito-borne arboviral disease in China.

PMID- 24745972
TI  - Quantitative assessment of upper limb motor function in Multiple Sclerosis using
      an instrumented Action Research Arm Test.
AB  - BACKGROUND: Arm impairment in Multiple Sclerosis (MS) is commonly assessed with
      clinical scales, such as Action Research Arm Test (ARAT) which evaluates the
      ability to handle and transport smaller and larger objects. ARAT provides a
      complete upper limb assessment, as it considers both proximal arm and hand, but
      suffers from subjectivity and poor sensitivity to mild impairment. In this study
      an instrumented ARAT is proposed to overcome these limitations and supplement the
      assessment of arm function in MS. METHODS: ARAT was executed by 12 healthy
      volunteers and 21 MS subjects wearing a single inertial sensor on the wrist.
      Accelerometers and gyroscopes signals were used to calculate the duration of each
      task and its sub-phases (reaching, manipulation, transport, release and return).
      A jerk index was computed to quantify movement smoothness. For each parameter, z
      scores were calculated to analyze the deviation from normative data. MS subjects
      were clinically assessed with ARAT score, Nine-Hole Peg test (9HPT) and Fahn
      Tremor Rating Scale (FTRS). RESULTS: ARAT tasks executed by MS patients were
      significantly slower (duration increase: 70%) and less smooth (jerk increase:
      16%) with respect to controls. These anomalies were mainly related to
      manipulation, transport and release sub-movements, with the former showing the
      greatest alterations. A statistically significant decrease in movement velocity
      and smoothness was also noticed in patients with normal ARAT score. Z-scores
      related to duration and jerk were strongly correlated with ARAT rating (r < 
      0.80, p < 0.001) and 9HPT (r < -0.75, p < 0.001) and were significantly different
      among MS sub-groups with different levels of arm impairments (p < 0.001).
      Moreover, Z-score related to manipulation-phase jerk was significantly correlated
      with the FTRS rating of intention tremor (r = 0.84, p < 0.001). CONCLUSIONS: The
      present study showed that the proposed method is able to discriminate between
      control and MS groups and to reveal subtle arm alterations not detectable from
      ARAT score. Validity was shown by high correlations between instrumental
      variables and clinical ratings. These results suggested that instrumented ARAT
      could be a valid quick and easy-to-use method for a sensitive quantification of
      arm function in MS. Inclusion of finger-mounted sensors could complement present
      findings and provide further indications about hand function in MS.

PMID- 24745973
TI  - A mystery unraveled: nontumorigenic pluripotent stem cells in human adult
      tissues.
AB  - INTRODUCTION: Embryonic stem cells and induced pluripotent stem cells have
      emerged as the gold standard of pluripotent stem cells and the class of stem cell
      with the highest potential for contribution to regenerative and therapeutic
      application; however, their translational use is often impeded by teratoma
      formation, commonly associated with pluripotency. We discuss a population of
      nontumorigenic pluripotent stem cells, termed Multilineage Differentiating Stress
      Enduring (Muse) cells, which offer an innovative and exciting avenue of
      exploration for the potential treatment of various human diseases. AREAS COVERED:
      This review discusses the origin of Muse cells, describes in detail their various
      unique characteristics, and considers future avenues of their application and
      investigation with respect to what is currently known of adult pluripotent stem
      cells in scientific literature. We begin by defining cell potency, then discuss
      both mesenchymal and various reported populations of pluripotent stem cells, and
      finally delve into Muse cells and the characteristics that set them apart from
      their contemporaries. EXPERT OPINION: Muse cells derived from adipose tissue
      (Muse-AT) are efficiently, routinely and painlessly isolated from human
      lipoaspirate material, exhibit tripoblastic differentiation both spontaneously
      and under media-specific induction, and do not form teratomas. We describe
      qualities specific to Muse-AT cells and their potential impact on the field of
      regenerative medicine and cell therapy.

PMID- 24745975
TI  - Integrated quantification and identification of aldehydes and ketones in
      biological samples.
AB  - The identification of unknown compounds remains to be a bottleneck of mass
      spectrometry (MS)-based metabolomics screening experiments. Here, we present a
      novel approach which facilitates the identification and quantification of
      analytes containing aldehyde and ketone groups in biological samples by adding
      chemical information to MS data. Our strategy is based on rapid autosampler-in
      needle-derivatization with p-toluenesulfonylhydrazine (TSH). The resulting TSH
      hydrazones are separated by ultrahigh-performance liquid chromatography (UHPLC)
      and detected by electrospray ionization-quadrupole-time-of-flight (ESI-QqTOF)
      mass spectrometry using a SWATH (Sequential Window Acquisition of all Theoretical
      Fragment-Ion Spectra) data-independent high-resolution mass spectrometry (HR-MS)
      approach. Derivatization makes small, poorly ionizable or retained analytes
      amenable to reversed phase chromatography and electrospray ionization in both
      polarities. Negatively charged TSH-hydrazone ions furthermore show a simple and
      predictable fragmentation pattern upon collision induced dissociation, which
      enables the chemo-selective screening for unknown aldehydes and ketones via a
      signature fragment ion (m/z 155.0172). By means of SWATH, targeted and
      nontargeted application scenarios of the suggested derivatization route are
      enabled in the frame of a single UHPLC-ESI-QqTOF-HR-MS workflow. The method's
      ability to simultaneously quantify and identify molecules containing aldehyde and
      ketone groups is demonstrated using 61 target analytes from various compound
      classes and a (13)C labeled yeast matrix. The identification of unknowns in
      biological samples is detailed using the example of indole-3-acetaldehyde. 

PMID- 24745976
TI  - Preparation methods of alginate nanoparticles.
AB  - This article reviews available methods for the formation of alginate nano
      aggregates, nanocapsules and nanospheres. Primarily, alginate nanoparticles are
      being prepared by two methods. In the "complexation method", complex formation on
      the interface of an oil droplet is used to form alginate nanocapsules, and
      complex formation in an aqueous solution is used to form alginate nano
      aggregates. In a second method w/o emulsification coupled with gelation of the
      alginate emulsion droplet can be used to form alginate nanospheres. We review
      advantages and disadvantages of these methods, and give an overview of the
      properties of the alginate particles produced with these methods. 

PMID- 24745977
TI  - Theoretical spectroscopy and photodynamics of a ruthenium nitrosyl complex.
AB  - Photoactive transition-metal nitrosyl complexes are particularly interesting as
      potential drugs that deliver nitric oxide (NO) upon UV-light irradiation to be
      used, e.g., in photodynamic therapy. It is well-recognized that quantum-chemical
      calculations can guide the rational design and synthesis of molecules with
      specific functions. In this contribution, it is shown how electronic structure
      calculations and dynamical simulations can provide a unique insight into the
      photodissociation mechanism of NO. Exemplarily, [Ru(PaPy3)(NO)](2+) is
      investigated in detail, as a prototype of a particularly promising class of
      photoactive metal nitrosyl complexes. The ability of time-dependent density
      functional theory (TD-DFT) to obtain reliable excited-state energies compared
      with more sophisticated multiconfigurational spin-corrected calculations is
      evaluated. Moreover, a TD-DFT-based trajectory surface-hopping molecular dynamics
      study is employed to reveal the details of the radiationless decay of the
      molecule via internal conversion and intersystem crossing. Calculations show that
      the ground state of [Ru(PaPy3)(NO)](2+) includes a significant admixture of the
      Ru(III)(NO)(0) electronic configuration, in contrast to the previously postulated
      Ru(II)(NO)(+) structure of similar metal nitrosyls. Moreover, the lowest singlet
      and triplet excited states populate the antibonding metal d -> piNO* orbitals,
      favoring NO dissociation. Molecular dynamics show that intersystem crossing is
      ultrafast (<10 fs) and dissociation is initiated in less than 50 fs. The
      competing relaxation to the lowest S1 singlet state takes place in less than 100
      fs and thus competes with NO dissociation, which mostly takes place in the higher
      lying excited triplet states. All of these processes are accompanied by bending
      of the NO ligand, which is not confined to any particular state. 

PMID- 24745974
TI  - Towards XNA nanotechnology: new materials from synthetic genetic polymers.
AB  - Nucleic acids display remarkable properties beyond information storage and
      propagation. The well-understood base pairing rules have enabled nucleic acids to
      be assembled into nanostructures of ever increasing complexity. Although
      nanostructures can be constructed using other building blocks, including peptides
      and lipids, it is the capacity to evolve that sets nucleic acids apart from all
      other nanoscale building materials. Nonetheless, the poor chemical and biological
      stability of DNA and RNA constrain their applications. Recent advances in nucleic
      acid chemistry and polymerase engineering enable the synthesis, replication, and
      evolution of a range of synthetic genetic polymers (XNAs) with improved chemical
      and biological stability. We discuss the impact of this technology on the
      generation of XNA ligands, enzymes, and nanostructures with tailor-made
      chemistry. 

PMID- 24745978
TI  - Comparison of laparoscopic sleeve gastrectomy leak rates in four staple-line
      reinforcement options: a systematic review.
AB  - OBJECTIVE: The study compared laparoscopic sleeve gastrectomy (LSG) staple-line
      leak rates of 4 prevalent surgical options: no reinforcement, oversewing,
      nonabsorbable bovine pericardial strips (BPS), and absorbable polymer membrane
      (APM). BACKGROUND: LSG is a multipurpose bariatric/metabolic procedure with
      effectiveness proven through the intermediate term. Staple-line leak is a severe
      complication of LSG for which no definitive method of prevention has been
      identified. METHODS: The systematic review study design was employed using
      Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement
      screening guidelines. Inclusion criteria centered on variables potentially
      relevant to LSG leak: leak rate, age, gender, calibrating bougie size, distance
      between pylorus and gastric transection line, overall complication rate, and
      mortality. Analysis of variance models were used to explore differences in select
      demographic and surgical technique variables characterizing each reinforcement
      group. An omnibus chi(2) test followed by independent Fisher's exact tests were
      used to compare leak rates. RESULTS: There were 659 articles identified; 41
      duplicates removed. Of 618 remaining articles, 324 did not meet inclusion
      criteria. Of the 294 remaining articles, 206 were eliminated (kin studies, those
      not reporting staple-line or leak incidence, those reporting discontinued
      products). There were 88 papers included in the analysis. Statistically
      significant differences were found between groups across demographic and surgical
      variables studied (p<0.001). There were 191 leaks in 8,920 patients; overall leak
      rate 2.1%. Leak rates ranged from 1.09% (APM) to 3.3% (BPS); APM leak rate was
      significantly lower than other groups (p< 0.05). CONCLUSION: Systematic review of
      88 included studies representing 8,920 patients found that the leak rate in LSG
      was significantly lower using APM staple-line reinforcement than oversewing, BPS
      reinforcement, or no reinforcement.

PMID- 24745979
TI  - Short-term outcomes of laparoscopic transcystic common bile duct exploration with
      discharge less than 24 hours.
AB  - BACKGROUND: Reducing the length of stay and discharge time for patients could
      benefit multiple hospital units by saving money, reducing waiting time, and
      providing the opportunity for more patients to be treated. However, no experience
      of laparoscopic transcystic common bile duct exploration (LTCBDE) with discharge
      less than 24 hours has been reported until now. The objective of this study was
      to assess the feasibility and safety of LTCBDE with discharge less than 24 hours.
      PATIENTS AND METHODS: A retrospective review showed that 34 of 111 patients
      scheduled in our institution were discharged less than 24 hours after LTCBDE
      between June 1 and December 31, 2011. A multimodal approach including appropriate
      preoperative assessment, education and counseling, early postoperative oral
      intake, and early mobilization was carried out. Outcomes were analyzed for
      patient demographics, postoperative stay, operation time, intraoperative
      bleeding, and reasons for failed LTCBDE. RESULTS: Of 111 patients admitted for
      LTCBDE, 34 patients were discharged within 24 hours postoperatively. This study
      population comprised 11 males and 23 females with a mean age of 54.6+/-14.7 years
      (range, 28-79 years). The mean postoperative stay was 20.21+/-0.39 hours. There
      were no postoperative complications or deaths during the hospital stay or at the
      follow-up 12 months postoperatively in these 34 patients. CONCLUSIONS: LTCBDE
      with discharge less than 24 hours is feasible and safe in selected patients with
      common bile duct stones of no more than three in number and no more than 6 mm in
      size. The benefit of the multimodal approach and LTCBDE may be synergistic,
      allowing a quick recovery of gastrointestinal function.

PMID- 24745980
TI  - Structure, function, and trafficking of SLC4 and SLC26 anion transporters.
AB  - The structure and function of the red cell anion exchanger 1 (AE1, Band 3,
      SLC4A1), the truncated kidney anion exchanger 1 (kAE1), and the other members of
      the SLC4 family of bicarbonate transporters are reviewed. Mutations in the AE1
      gene cause human diseases like Southeast Asian ovalocytosis and hereditary
      spherocytosis in the red cell and distal renal tubular acidosis in the kidney.
      These mutations affect the folding, trafficking, and functional expression of
      these membrane glycoproteins. In the SLC26 family of anion transporters,
      mutations also cause trafficking defects and human disease. Membrane
      glycoproteins are cotranslationally N-glycosylated in the endoplasmic reticulum
      (ER) and when properly folded, traffic via the secretory pathway to their final
      destination such as the plasma membrane. Misfolded glycoproteins are retained in
      ER and are targeted for degradation by the proteasome following
      retrotranslocation and ubiquitinylation. ER chaperones, like membrane-bound
      calnexin, interact transiently with glycoproteins and are part of the quality
      control system that monitors the folding of glycoproteins during their
      biosynthesis. Recent results have indicated that it is possible to "correct"
      trafficking defects caused by some mutations in the SLC4 and 26 families through
      the use of small molecules that interfere with the interaction of glycoproteins
      with the components of the quality control system. This review summarizes the
      current knowledge on structure and function of anion transporters from the SLC4
      and SLC26 families, and the effect of mutations on their trafficking and
      functional expression. 

PMID- 24745981
TI  - Structural dynamics and regulation of the mammalian SLC9A family of Na+/H+
      exchangers.
AB  - Mammalian Na+/H+ exchangers of the SLC9A family are widely expressed and involved
      in numerous essential physiological processes. Their primary function is to
      mediate the 1:1 exchange of Na+ for H+ across the membrane in which they reside,
      and they play central roles in regulation of body, cellular, and organellar pH.
      Their function is tightly regulated through mechanisms involving interactions
      with multiple protein and lipid-binding partners, phosphorylations, and other
      posttranslational modifications. Biochemical and mutational analyses indicate
      that the SLC9As have a short intracellular N-terminus, 12 transmembrane (TM)
      helices necessary and sufficient for ion transport, and a C-terminal cytoplasmic
      tail region with essential regulatory roles. No high-resolution structures of the
      SLC9As exist; however, models based on crystal structures of the bacterial NhaAs
      support the 12 TM organization and suggest that TMIV and XI may form a central
      part of the ion-translocation pathway, whereas pH sensing may involve TMII, TMIX,
      and several intracellular loops. Similar to most ion transporters studied, SLC9As
      likely exist as coupled dimers in the membrane, and this appears to be important
      for the well-studied cooperativity of H+ binding. The aim of this work is to
      summarize and critically discuss the currently available evidence on the
      structural dynamics, regulation, and binding partner interactions of SLC9As,
      focusing in particular on the most widely studied isoform, SLC9A1/NHE1. Further,
      novel bioinformatic and structural analyses are provided that to some extent
      challenge the existing paradigm on how ions are transported by mammalian SLC9As.

PMID- 24745982
TI  - Vesicular neurotransmitter transporters: mechanistic aspects.
AB  - Secondary transporters driven by a V-type H+-ATPase accumulate nonpeptide
      neurotransmitters into synaptic vesicles. Distinct transporter families are
      involved depending on the neurotransmitter. Monoamines and acetylcholine on the
      one hand, and glutamate and ATP on the other hand, are accumulated by SLC18 and
      SLC17 transporters, respectively, which belong to the major facilitator
      superfamily (MFS). GABA and glycine accumulate through a common SLC32 transporter
      from the amino acid/polyamine/organocation (APC) superfamily. Although
      crystallographic structures are not yet available for any vesicular transporter,
      homology modeling studies of MFS-type vesicular transporters based on distantly
      related bacterial structures recently provided significant advances, such as the
      characterization of substrate-binding pockets or the identification of spatial
      clusters acting as hinge points during the alternating-access cycle. However,
      several basic issues, such as the ion stoichiometry of vesicular amino acid
      transporters, remain unsettled.

PMID- 24745985
TI  - SLC22, SLC44, and SLC47 transporters--organic anion and cation transporters:
      molecular and cellular properties.
AB  - Transporters within the SLC22, SLC44, and SLC47 families of solute carriers
      mediate transport of a structurally diverse array of organic electrolytes, that
      is, molecules that are generally charged (cationic, anionic, or zwitterionic) at
      physiological pH. Transporters in the SLC22 family--all of which are members of
      the major facilitator superfamily (MFS) of transporters--represent a
      mechanistically diverse set of processes, including the organic anion
      transporters (OATs and URAT1) that physiologically operate as organic anion (OA)
      exchangers, the organic cation transporters (OCTs) that operate as electrogenic
      uniporters of organic cations (OCs), and the so-called "novel" organic cation
      transporters (OCTNs) that support Na-cotransport of selected zwitterions. Whereas
      the OCTNs display a high degree of substrate selectivity, the physiological
      hallmark of the OATs and OCTs is their multiselectivity--consistent with a
      principal role in renal and hepatic clearance of a wide array of both endogenous
      and xenobiotic compounds. SLC47 consists of members of the multidrug and toxin
      extruder (MATE) family, which are carriers that are obligatory exchangers and
      that physiologically support electroneutral H+ exchange. The MATEs also display a
      characteristic multiselectivity and are frequently paired with OCTs to mediate
      transepithelial OC secretion, with the OCTs typically supporting basolateral OC
      entry and the MATEs supporting apical OC efflux. The SLC44 family contains the
      choline transporter-like (CTL) transporters. Largely restricted to choline and a
      limited set of structural congeners, the CTLs appear to support the Na
      independent, electrogenic uniport of choline, thereby providing choline for
      membrane biogenesis. The solution of X-ray crystal structures of representative
      prokaryotic MFS and MATE transporters has led to the development of homology
      models of mammalian OAT, OCT, and MATE transporters that, in turn, have
      supplemented studies of the molecular basis of the complex interactions of
      ligands with these multiselective proteins.

PMID- 24745983
TI  - Biology of the major facilitative folate transporters SLC19A1 and SLC46A1.
AB  - This chapter focuses on the biology of the major facilitative membrane folate
      transporters, the reduced folate carrier (RFC), and the proton-coupled folate
      transporter (PCFT). Folates are essential vitamins, and folate deficiency
      contributes to a variety of heath disorders. RFC is ubiquitously expressed and is
      the major folate transporter in mammalian cells and tissues. PCFT mediates
      intestinal absorption of dietary folates. Clinically relevant antifolates such as
      methotrexate (MTX) are transported by RFC, and the loss of RFC transport is an
      important mechanism of MTX resistance. PCFT is abundantly expressed in human
      tumors and is active under pH conditions associated with the tumor
      microenvironment. Pemetrexed (PMX) is an excellent substrate for PCFT as well as
      for RFC. Novel tumor-targeted antifolates related to PMX with selective membrane
      transport by PCFT over RFC are being developed. The molecular picture of RFC and
      PCFT continues to evolve relating to membrane topology, N-glycosylation,
      energetics, and identification of structurally and functionally important domains
      and amino acids. The molecular bases for MTX resistance associated with loss of
      RFC function, and for the rare autosomal recessive condition, hereditary folate
      malabsorption (HFM), attributable to mutant PCFT, have been established. From
      structural homologies to the bacterial transporters GlpT and LacY, homology
      models were developed for RFC and PCFT, enabling new mechanistic insights and
      experimentally testable hypotheses. RFC and PCFT exist as homo-oligomers, and
      evidence suggests that homo-oligomerization of RFC and PCFT monomeric proteins
      may be important for intracellular trafficking and/or transport function. Better
      understanding of the structure and function of RFC and PCFT should facilitate the
      rational development of new therapeutic strategies for cancer as well as for HFM.

PMID- 24745986
TI  - The SLC24 family of K+-dependent Na+-Ca2+ exchangers: structure-function
      relationships.
AB  - The human SLC24 gene family contains five members encoding the NCKX1-5 proteins
      that function as K(+)-dependent Na+-Ca2+ exchangers. NCKX proteins have been
      shown to play critical roles in retinal rod and cone photoreceptors, olfactory
      neurons, epidermal melanocytes, and the retinal pigment epithelium. NCKX
      transcripts are also found in many other tissues, in particular throughout the
      brain, but their specific physiological roles yet need to be elucidated in most
      cases. Here, we focus on our current knowledge of NCKX transport function as has
      been described in detail only for in situ NCKX1 in the outer segments of retinal
      rod photoreceptors and on structure-function relationships elucidated for the
      NCKX2 isoform after expression of its (mutated) cDNA in cell lines.

PMID- 24745984
TI  - Organic anion-transporting polypeptides.
AB  - Organic anion-transporting polypeptides or OATPs are central transporters in the
      disposition of drugs and other xenobiotics. In addition, they mediate transport
      of a wide variety of endogenous substrates. The critical role of OATPs in drug
      disposition has spurred research both in academia and in the pharmaceutical
      industry. Translational aspects with clinical questions are the focus in
      academia, while the pharmaceutical industry tries to define and understand the
      role these transporters play in pharmacotherapy. The present overview summarizes
      our knowledge on the interaction of food constituents with OATPs and on the OATP
      transport mechanisms. Further, it gives an update on the available information on
      the structure-function relationship of the OATPs and, finally, covers the
      transcriptional and posttranscriptional regulation of OATPs. 

PMID- 24745987
TI  - Antiporters of the mitochondrial carrier family.
AB  - The eukaryotic transport protein family SLC25 consists of mitochondrial carriers
      (MCs) that are recognized on the sequence level by a threefold repeated and
      conserved signature motif. The majority of MCs characterized so far catalyzes
      strict exchanges of substrates across the mitochondrial inner membrane. The
      substrates are nucleotides, metabolic intermediates, and cofactors that are
      required in cytoplasmic and matrix metabolism. This review summarizes and
      discusses the current knowledge of the antiport mechanism(s) of MCs that has been
      deduced from determining transport characteristics and by analyzing structural,
      sequence, and mutagenesis data. The mode of transport varies among different MCs
      with respect to how the substrate translocation depends on the electrical and pH
      gradients across the mitochondrial inner membrane, for example, the ADP/ATP
      carrier is electrogenic (electrophoretic), the GTP/GDP carrier is dependent on
      the pH gradient, the aspartate/glutamate carrier is dependent on both, and the
      oxoglutarate/malate carrier is independent of them. The structure of the bovine
      ADP/ATP carrier consists of a six-transmembrane alpha-helix bundle with a pseudo
      threefold symmetry and a closed matrix gate. By using this structure as a
      template in homology modeling, residues engaged in substrate binding and the
      formation of a cytoplasmic gate in MCs have been proposed. The functional
      importance of the residues of the binding site, the matrix, and the cytoplasmic
      gates is supported by transport activities of different MCs with single point
      mutations. Cumulative evidence has been used to postulate a general transport
      mechanism for MCs. 

PMID- 24745988
TI  - The families of zinc (SLC30 and SLC39) and copper (SLC31) transporters.
AB  - The solute carriers families 30 (SLC30; ZnT), 39 (SLC39; ZIP), and 31 (SLC31;
      CTR) are involved in the essential maintenance of cellular zinc (Zn2+) and copper
      (Cu2+) homeostasis, respectively. ZnTs mediate Zn2+ extrusion from cells
      (SLC30A1) or transport Zn2+ into organelles and secretory vesicles/granules
      (SLC30A2-SLC30A8). SLC39 family members are predominantly localized to the cell
      membrane where they perform Zn2+ uptake and increase the availability of
      cytosolic Zn2+. SLC39A1 is ubiquitously expressed, whereas other ZIP transporters
      (e.g., SLC39A2 and SLC39A3) show a more tissue-restricted expression consistent
      with organ-specific functions of these proteins. The members A1 (CTR1) and A2
      (CTR2) of the SLC31 family of solute carriers belong to a network of proteins
      that acts to regulate the intracellular Cu2+ concentration within a certain
      range. SLC31A1 is predominantly localized to the plasma membrane, whereas SLC31A2
      is mainly found in intracellular membranes of the late endosome and lysosome. The
      specific function of SLC31A2 is not known. SLC31A1 is ubiquitously expressed and
      has been characterized as a high-affinity importer of reduced copper (Cu+). Cu2+
      transport function of CTR proteins is associated with oligomerization; SLC31A1
      trimerizes and thereby forms a channel-like structure enabling Cu2+ translocation
      across the cell membrane. The molecular characteristics and structural details
      (e.g., membrane topology, conserved Zn2+, and Cu2+ binding sites) and mechanisms
      of translational and posttranslational regulation of expression and/or activity
      have been described for SLC30 and SLC39 family members, and for SLC31A1. For
      SLC31A1, data on tissue-specific functions (e.g., in the intestine, heart, and
      liver) are also available. A link between SLC31A1, immune function, and disorders
      such as Alzheimer's disease or cancer makes the protein a candidate therapeutic
      target. In secretory tissues (e.g., the mammary gland and pancreas), Zn2+
      transporters of SLC families 30 and 39 are involved in specific functions such as
      insulin synthesis and secretion, metallation of digestive proenzymes, and
      transfer of nutrients into milk. Defective or dysregulated Zn2+ metabolism in
      these organs is associated with disorders such as diabetes and cancer, and
      impaired Zn2+ secretion into milk.

PMID- 24745990
TI  - SLC41 transporters--molecular identification and functional role.
AB  - The solute carrier family 41 (SLC41) encompasses three members A1, A2, and A3.
      Based on their distant homology to the bacterial Mg2+ channel MgtE, all have been
      linked to Mg2+ transport. There is only very limited knowledge on the molecular
      biology and exact functions of SLC41A2 and SLC41A3. SLC41A1 is ubiquitously
      expressed and data on its functional and molecular properties, regulation,
      complex-forming ability, and spectrum of binding partners are available. SLC41A1
      was recently identified as being the Na+/Mg2+ exchanger (NME)-a predominant Mg2+
      efflux system. Mg2+-dependent and hormonal regulation of NME activity is now
      known to depend on the intracellular N terminus of SLC41A1 that is involved in
      Mg2+ sensing and contains phosphorylation sites for protein kinase (PK) A and
      PKC. Data showing a link between SLC41A1 and human disorders such as Parkinson's
      disease, nephronophthisis (induced by the null mutation c.698G>T in renal
      SLC41A1), and preeclampsia make the protein a candidate therapeutic target.

PMID- 24745989
TI  - The SLC37 family of sugar-phosphate/phosphate exchangers.
AB  - The SLC37 family members are endoplasmic reticulum (ER)-associated sugar
      phosphate/phosphate (P(i)) exchangers. Three of the four members, SLC37A1,
      SLC37A2, and SLC37A4, function as Pi-linked glucose-6-phosphate (G6P) antiporters
      catalyzing G6P:P(i) and P(i):P(i) exchanges. The activity of SLC37A3 is unknown.
      SLC37A4, better known as the G6P transporter (G6PT), has been extensively
      characterized, functionally and structurally, and is the best characterized
      family member. G6PT contains 10 transmembrane helices with both N and C termini
      facing the cytoplasm. The primary in vivo function of the G6PT protein is to
      translocate G6P from the cytoplasm into the ER lumen where it couples with either
      the liver/kidney/intestine-restricted glucose-6-phosphatase-alpha (G6Pase-alpha
      or G6PC) or the ubiquitously expressed G6Pase-beta (or G6PC3) to hydrolyze G6P to
      glucose and P(i). The G6PT/G6Pase-alpha complex maintains interprandial glucose
      homeostasis, and the G6PT/G6Pase-beta complex maintains neutrophil energy
      homeostasis and functionality. G6PT is highly selective for G6P and is
      competitively inhibited by cholorogenic acid and its derivatives. Neither SLC37A1
      nor SLC37A2 can couple functionally with G6Pase-alpha or G6Pase-beta, and the
      antiporter activities of SLC37A1 or SLC37A2 are not inhibited by cholorogenic
      acid. Deficiencies in G6PT cause glycogen storage disease type Ib (GSD-Ib), a
      metabolic and immune disorder. To date, 91 separate SLC37A4 mutations, including
      39 missense mutations, have been identified in GSD-Ib patients. Characterization
      of missense mutations has yielded valuable information on functionally important
      residues in the G6PT protein. The biological roles of the other SLC37 proteins
      remain to be determined and deficiencies have not yet been correlated to
      diseases.

PMID- 24745991
TI  - Preface.

PMID- 24745992
TI  - Spinal hyperostosis as an important sign indicating spine injuries on postmortem
      computed tomography.
AB  - Although spine injuries are not always detectable on postmortem computed
      tomography (PMCT), spinal hyperostosis, an important risk factor for spine
      injury, is relatively easily detectable on PMCT. We therefore examined the
      utility of the detection of spinal hyperostosis on PMCT as an indicator of spine
      injury. Full-body PMCT images of 88 autopsy cases with a bruise on the face or
      forehead but no identifiable skull fracture were reviewed prior to autopsy for
      the identification and classification of spinal hyperostosis. Spine injuries were
      observed in 56.0% of cases with spinal hyperostosis and 1.6% of cases without
      spinal hyperostosis. Among the cases with spinal hyperostosis, spine injuries
      were observed in 66.7% of cases at stage 2 or 3 and in 88.9% of cases at stage 3.
      Spine injuries were diagnosed on PMCT in 33.3% of cases prior to autopsy. A
      significant association was found between spinal hyperostosis and presence of
      spine injury that cannot be detected on PMCT, indicating that the identification
      of spinal hyperostosis on PMCT may assist in detecting spine injuries. This
      finding suggests that investigation of the presence of spine injury based on the
      identification of spinal hyperostosis on PMCT may assist in determining the
      correct cause of death by autopsy. 

PMID- 24745995
TI  - Anastomotic leakage and presacral abscess formation after locally advanced rectal
      cancer surgery: Incidence, risk factors and treatment.
AB  - PURPOSE OF THE STUDY: Anastomotic leakage (AL) and presacral abscess (PA) after
      rectal cancer surgery are a major concern for the colorectal surgeon. In this
      study, incidence, prognosis and treatment was assessed. METHODS: Patients
      operated on in our institute, between 1994 and 2011, for locally advanced rectal
      cancer (LARC, T3+/T4M0) were included. Morbidity was scored using the Clavien
      Dindo classification. Prognostic factors were analysed using binary logistic
      regression. RESULTS: 517 patients were included after a low anterior resection (n
      = 219) or abdominoperineal resection (n = 232). AL occurred in 25 patients
      (11.4%); 50 patients (9.7%) developed a PA. We identified intraoperative blood
      loss >=4500 cc (p = 0.038) and the era of surgery; patients operated on before
      the year 2006 (p = 0.042); as risk factors for AL. The time between last day of
      neo-adjuvant treatment and surgery, <8 weeks is significantly associated with the
      development of PA (p = 0.010). CONCLUSIONS: In our population of LARC patients we
      found an incidence of 9.7% PA and 11.4% AL, with a 12% mortality rate for AL,
      which is comparable to surgery in general colorectal cancer. Increased
      intraoperative blood loss and surgery prior to 2006 are associated with AL.
      Increased intraoperative blood loss and a timing interval <8 weeks increases the
      risk of PA formation.

PMID- 24745996
TI  - Extralevator abdomino-perineal excision (ELAPE) or abdomino-sacral amputation of
      the rectum (ASAR): revitalized approach for low rectal carcinoma described by
      Tadeusz Koszarowski in the 50s.

PMID- 24745997
TI  - Response to: "hyperthermic intraperitoneal chemotherapy in epithelial ovarian
      cancer should be proposed in eight time points".

PMID- 24745998
TI  - Spleen stroma maintains progenitors and supports long-term hematopoiesis.
AB  - Hematopoietic stem/progenitor cells (HSPC) differentiate in the context of
      stromal niches producing cells of multiple lineages. Limited success has been
      achieved in the past with induction of hematopoiesis in vitro. Previously, spleen
      long-term stromal cultures (LTC) were shown to continuously support restricted
      hematopoiesis for production of novel dendritic-like cells (LTC-DC). An in vivo
      equivalent dendritic cell type was then described which is specific for spleen.
      The in vivo counterpart cell was termed 'L-DC' and represents a dendritic-like
      CD11c(lo)CD11b(hi)CD8alpha-MHC-II- cell which differs phenotypically and
      functionally from monocytes/macrophages and conventional and plasmacytoid DC.
      Splenic stroma is now shown to maintain HSPC and to support their restricted in
      vitro differentiation to give this 'L-DC' subset. In order to characterise
      progenitors of this distinct cell type, LTC were analysed for cell subsets
      produced, and these subsets sorted and assessed for hematopoietic potential in
      subsequent co-cultures over STX3 stroma. Progenitors were defined as a lineage
      (Lin)(-)ckit(lo) subset reflecting HSPC. Furthermore, when Lin(
      )ckit(hi)Sca1(+)Flt3(-) HSPC were sorted from bone marrow, they colonised splenic
      stroma with long-term production of L-DC. The maintenance of HSPC by splenic
      stroma was confirmed when non-adherent cells collected from LTC showed
      oligopotent reconstitution of the hematopoietic compartment of lethally
      irradiated mice. All data support a model whereby spleen houses a niche for HSPC
      in the resting state, with production of progenitors, and their differentiation
      to give tissue-specific antigen presenting cells. 

PMID- 24745999
TI  - Azithromycin for patients with frequent COPD exacerbations.

PMID- 24746000
TI  - Azithromycin maintenance treatment in patients with frequent exacerbations of
      chronic obstructive pulmonary disease (COLUMBUS): a randomised, double-blind,
      placebo-controlled trial.
AB  - BACKGROUND: Macrolide resistance is an increasing problem; there is therefore
      debate about when to implement maintenance treatment with macrolides in patients
      with chronic obstructive pulmonary disease (COPD). We aimed to investigate
      whether patients with COPD who had received treatment for three or more
      exacerbations in the previous year would have a decrease in exacerbation rate
      when maintenance treatment with azithromycin was added to standard care. METHODS:
      We did a randomised, double-blind, placebo-controlled, single-centre trial in The
      Netherlands between May 19, 2010, and June 18, 2013. Patients (>=18 years) with a
      diagnosis of COPD who had received treatment for three or more exacerbations in
      the previous year were randomly assigned, via a computer-generated randomisation
      sequence with permuted block sizes of ten, to receive 500 mg azithromycin or
      placebo three times a week for 12 months. Randomisation was stratified by use of
      long-term, low-dose prednisolone (<=10 mg daily). Patients and investigators were
      masked to group allocation. The primary endpoint was rate of exacerbations of
      COPD in the year of treatment. Analysis was by intention to treat. This study is
      registered with ClinicalTrials.gov, number NCT00985244. FINDINGS: We randomly
      assigned 92 patients to the azithromycin group (n=47) or the placebo group
      (n=45), of whom 41 (87%) versus 36 (80%) completed the study. We recorded 84
      exacerbations in patients in the azithromycin group compared with 129 in those in
      the placebo group. The unadjusted exacerbation rate per patient per year was 1.94
      (95% CI 1.50-2.52) for the azithromycin group and 3.22 (2.62-3.97) for the
      placebo group. After adjustment, azithromycin resulted in a significant reduction
      in the exacerbation rate versus placebo (0.58, 95% CI 0.42-0.79; p=0.001). Three
      (6%) patients in the azithromycin group reported serious adverse events compared
      with five (11%) in the placebo group. During follow-up, the most common adverse
      event was diarrhoea in the azithromycin group (nine [19%] patients vs one [2%] in
      the placebo group; p=0.015). INTERPRETATION: Maintenance treatment with
      azithromycin significantly decreased the exacerbation rate compared with placebo
      and should therefore be considered for use in patients with COPD who have the
      frequent exacerbator phenotype and are refractory to standard care. FUNDING:
      SoLong Trust.

PMID- 24746001
TI  - [Study of distribution and influencing factors of lead and cadmium in whole blood
      and urine among population in 8 provinces in China].
AB  - OBJECTIVE: To evaluate the levels of lead (Pb) and cadmium (Cd) in blood and
      urine among general population in China, and thereby analyze their prevalent
      features. METHODS: A total of 18 120 subjects from general population aged 6-60
      years were recruited from 24 districts in 8 provinces in eastern, central and
      western China mainland from 2009 to 2010, by cluster random sampling method. The
      blood samples and urine samples of these people were collected. The questionnaire
      survey was used to collect the information of the living environment and health
      conditions.Inductive coupled plasma mass spectrometry was applied to test the Pb
      and Cd levels in the samples, and the distribution of Pb and Cd in blood and
      urine for different ages, genders, areas and life habits were then analyzed.
      RESULTS: Among the general population in China, the geometric mean (GM) of blood
      Pb concentration was 34.9 ug/L; the GM of blood Pb in male and female groups were
      40.1 and 30.4 ug/L (Z = -28.05, P < 0.05), respectively; the GM from eastern,
      central and western China were 31.2, 38.8 and 58.9 ug/L (chi(2) = 1 483.33, P <
      0.05) , respectively. The GM of urine Pb of the whole population was 1.05
      ug/L;while the GM in male and female groups were 1.06 ug/L and 1.05 ug/L (Z = 
      0.73, P > 0.05) , respectively;the values from eastern, central and western China
      were 0.76, 2.85 and 3.22 ug/L (chi(2) = 1 982.11, P < 0.05), respectively. The GM
      of blood Cd concentration among general population was 0.49 ug/L; and the values
      in male and female group were 0.60 and 0.41 ug/L (Z = -11.79, P < 0.05) ,
      respectively; the GM from eastern, central and western China were 0.45, 0.65 and
      0.67 ug/L (chi(2) = 69.87, P < 0.05), respectively; the GM of urine Cd
      concentration of the whole population was 0.28 ug/L, while the GM in male and
      female groups were 0.29 and 0.28 ug/L (Z = -3.86, P < 0.05), respectively; the
      values from eastern, central and western China were 0.29,0.42 and 0.18 ug/L
      (chi(2) = 402.76, P < 0.05), respectively. the Spearman's rank correlation
      coefficient for Cd in blood and Cd in urine was 0.22, for Pb in blood and Pb in
      urine was 0.21. Both the correlations were statistic significant (P < 0.05).
      CONCLUSION: The Pb and Cd levels in blood and urine were relatively higher among
      general population in China varying by gender and area. There were positive
      correlations between Pb and Cd levels in blood and those in urine.

PMID- 24746002
TI  - [Study of distribution and influencing factors of arsenic in whole blood and
      urine among population in 8 provinces in China].
AB  - OBJECTIVE: To evaluated the levels of arsenic (As) in blood and urine among
      general population in China and analyze its influencing factors. METHODS: A total
      of 18 120 subjects from general population aged 6-60 years were recruited from 24
      districts in 8 provinces in eastern, central and western China mainland from 2009
      to 2010, by cluster random sampling method. Blood samples and urine samples were
      collected, the information of the life-style was collected by
      questionnaire.Inductive coupled plasma mass spectrometry was applied to test the
      As level in the samples, and the distribution of As in blood and urine for
      different ages, genders, areas and life habits were then analyzed. RESULTS: The
      geometric mean (GM) of blood As concentration among general population was 2.33
      ug/L;the GM of blood As in male (2.35 ug/L) was higher than and female (2.30
      ug/L) (Z = -1.42, P < 0.05); from eastern, central to western China, the blood As
      level were 2.94, 1.30 and 0.98 ug/L (chi(2) = 643.22, P < 0.05) , respectively;
      the GM in smokers (2.84 ug/L) was higher than non-smokers (2.27) (Z = -6.28, P <
      0.05) ;the seafood consumer had a higher blood As level (2.59 ug/L) than people
      not consuming seafood (1.47 ug/L) (Z = -23.68, P < 0.05). The urine As level of
      the whole population was 13.72 ug/L;while its GM in male (14.10 ug/L) was higher
      than female (13.33 ug/L) (Z = -3.94, P < 0.05); the values from eastern, central
      to western China were 14.14, 16.02 and 9.57 ug/L (chi(2) = 353.89, P < 0.05),
      respectively;the level in smokers (16.06 ug/L) was higher than nonsmokers (13.70
      ug/L) (Z = -2.63, P < 0.05); the level in seafood consumers (14.82 ug/L) was
      higher than people not consuming seafood (10.99 ug/L) (Z = -3.20, P < 0.05). The
      blood As level had a positive correlation with urine As level (correlation
      coefficient:0.285, P < 0.05). CONCLUSION: The As level in blood and urine varied
      by gender and area among general population in China, and related to life-styles.
      There was a positive correlation between As level in blood and that in urine.

PMID- 24746003
TI  - [Polycyclic aromatic hydrocarbons monohydroxy metabolites level in urine of
      general population in eight provinces of China].
AB  - OBJECTIVE: To assess the levels of polycyclic aromatic hydrocarbons monohydroxy
      metabolites in urine of general population in China among 8 provinces, provide
      the baseline of the metabolites in the general population. METHODS: From 2009 to
      2010, 18 120 subjects of general population aged 6-60 years old were recruited
      from 24 areas among 8 provinces in east, west and central areas of China mainland
      by cluster random sampling. The information of the living environment and health
      condition were collected by questionnaire and spot urine samples were collected,
      4 680 urine samples were analysed by high performance liquid chromatography with
      tandem mass spectrometry, and monohydroxy metabolites distribution in urine among
      groups of gender and ages were analysed. RESULTS: Geometric means (GM) of 2
      naphthol, 1-naphthol, 3-phenanthrol and 1-hydroxypyrene concentration in urine
      (95%CI) were 1.85 (1.75-1.95), 1.55 (1.50-1.61), 0.57 (0.54-0.59) and 0.82 (0.78
      0.85) ug/L, respectively;and median are 2.44, <0.50, 0.72 and 0.90 ug/L,
      respectively. The concentration between male and female were significantly
      different (P < 0.01), and the concentration among the groups of population were
      significantly different (P < 0.01), the GM of 2-naphthol among the groups of
      population aged 6-12, 13-16, 17-20, 21-30, 31-45 and 46-60 years old were 1.60,
      1.56, 1.69, 2.23, 1.91 and 1.86 ug/L (chi(2) = 17.90, P < 0.01), the GM of 1
      naphthol in the groups were 1.30, 1.16, 1.53, 1.68, 1.80 and 1.52 ug/L (chi(2) =
      76.22, P < 0.01), the GM of 3-phenanthrol in the groups were 0.78, 0.76, 0.55,
      0.42, 0.50 and 0.99 ug/L (chi(2) = 66.48, P < 0.01), the GM of 1-hydroxypyrene in
      the groups were 0.77,0.64, 1.00, 0.84, 0.84 and 0.57 ug/L (chi(2) = 51.48, P <
      0.01), respectively. CONCLUSION: The distribution of monohydroxy metabolites
      levels in urine of general population were different, it provided a basic data
      for the further study of polycyclic aromatic hydrocarbons biomonitoring in the
      population.

PMID- 24746004
TI  - [Distribution of copper and zinc in blood among general population from 8
      provinces in China].
AB  - OBJECTIVE: To investigate the level of zinc (Zn) and copper (Cu) in whole blood
      among general population from 8 provinces in China, and to analyze the
      characteristics of distribution among different regions. METHODS: This cross
      sectional study was performed in 8 provinces from eastern, middle and western
      China between 2009 and 2010, including 13 110 subjects from 24 regions, and the
      blood and urine samples were collected. The ICP-MS was applied to test the
      content of ICP-MS in blood samples, and the results were used to analyze the
      characteristics of contents and distributions of Zn and Cu among population from
      different ages, genders and regions groups. RESULTS: Totally, the mean (95%CI)
      contents of Cu and Zn in blood were 795 (791-799)ug/L and 3 996(3 976-4 015)
      ug/L, respectively. The characteristics of distribution of Cu content were as
      followed, the content of males were lower than it of females (male:767 ug/L;
      female: 822 ug/L, t = -13.302, P < 0.01). The contents of blood Cu in groups of
      people aging 6-12, 13-16, 17-20, 21-30, 31-45 and 46-60 years old were separately
      860(853-868), 758(748-769), 734(728-734), 782(774-790), 811(795-827) and 820(815
      826) ug/L. The differences showed statistical significance (F = 78.77, P < 0.01).
      The blood Cu content of people in eastern China (800ug/L) were also significantly
      higher than it in middle (774 ug/L)and western China (782 ug/L) (F = 10.94, P <
      0.01). Distribution of blood Zn content showed characteristics as follows: the Zn
      content was higher in males than in females (male 4 085 ug/L and female 3 908
      ug/L, t = 8.78, P < 0.01). The contents of blood Zn in groups of people aging 6
      12, 13-16, 17-20, 21-30, 31-45 and 46-60 years old were separately 3 306 (3 261-3
      350), 3 888 (3 839-3 937), 3 948 (3 902-3 994), 4 272(4 228-4 315), 4 231(4 180-4
      281) and 4 250 (4 205-4 294)ug/L, which showed significant statistical
      differences (F = 233.68, P < 0.01). The blood Zn content of people in eastern
      China (3 938 ug/L) were significantly lower than it in middle (4 237 ug/L)and
      western China (4 105 ug/L) (F = 53.16, P < 0.01). In addition, the study also
      compared the relation between content of Cu and Zn and the frequency of eating
      seafood. The results found that the frequency of eating seafood could influence
      the content of Cu and Zn (Cu: F = 13.54, P < 0.01; Zn: F = 200.20, P < 0.01).
      CONCLUSION: The contents and distributions of Cu and Zn in blood differs among
      people from different groups in ages, genders and regions. The baseline data of
      this study provided reliable scientific evidence for further research.

PMID- 24746005
TI  - [The distribution of 24 elements in urine from Shenzhen residents].
AB  - OBJECTIVE: This study aims to describe the distribution of 24 elements in urine
      of Shenzhen residents. METHODS: According to the principle of equal probability
      of selection method, in March 2011 to July, total 11 communities were chosen as
      the basic sampling unit in Shenzhen, with 1 to 2 communities in each of the
      municipal district. Then 75 families from each sampling unit were selected using
      systematic sampling method. In total, 2 200 subjects were chosen. 10-20 ml
      morning middle stream urine was collected, and then detected the concentration of
      Li, Be, Sr, Cd, Cs, Ta, Pb, V, Cr, Mn, Fe, Ni, Co, Cu, Zn, Sn, Sb, Te, As, Se,
      Ru, Na, Mg, K, and analysed the discrepancies between gender and among age
      groups. RESULTS: In those 24 elements, the concentration of Na was highest, the
      medians( 5th percentile (P 5), 95th percentile (P 95)) were 2 845.78 (920.29, 5
      974.53) mg/L; Be was lowest, the result was 0.10(0.01, 0.58) ug/L. Except
      macroelements of Na (2 921.97 (985.14, 6 201.51) mg/L), Mg (48.20(8.23, 132.41)
      mg/L), K (2 323.20(683.98, 5 657.47) mg/L), the content of Rb was highest,
      3.31(9.82, 7.83) mg/L, followed by Zn, 454.54(113.90, 1 320.00) ug/L, the content
      of V, Cr, Mn, Se, Tl was pretty low, the median of those elements all less than
      1.00 ug/L. Statistically significant differences were found between genders and
      among age groups in Pb, Fe, Se (gender: Z values were 4.51, 2.53, 4.00, all P
      values were <0.05; age groups: H values were 55.67, 129.42, 18.46, all P values
      were <0.05). The medians(P5, P95) were 2.04 (0.57, 5.31), 202.88 (48.66, 564.90),
      49.68 (14.34, 150.91) ug/L. The values of male were 2.22 (0.71, 5.33), 212
      (47.50, 567.29), 53.42 (16.20, 160.63) ug/L. And the results of female were 1.95
      (0.51, 5.24), 193.69 (49.52, 562.31), 46.62 (12.65, 142.80) ug/L; the values of
      less than 17 years old subjects were 1.66 (0.38, 3.77), 106.13 (26.69, 459.81),
      51.86 (15.86, 169.71) ug/L; the results were 1.96 (0.52, 5.08), 209.83(52.87,
      577.81), 54.14 (15.14, 144.11) ug/L in the group of 18 to 40 years old; in the 41
      to 65 years old group, the values were 2.29 (0.78, 5.85), 228.15 (67.74, 615.16),
      46.62 (13.95, 143.57) ug/L, the results were 2.19 (0.65, 5.69), 195.92(55.17,
      490.24), 43.16 (12.42, 155.36) ug/L in 66 years old and more group. CONCLUSION:
      Among these 24 elements in urine of Shenzhen residents, the Na concentration was
      highest, while Be was lowest. Elements (Pb, Fe, Se) differed with the condition
      of gender and age groups. So we should take all these factors into account to
      establish their reference values.

PMID- 24746006
TI  - [The relationship between salt consumption and blood pressure among residents in
      Shandong province, China].
AB  - OBJECTIVE: To study the relationship between salt consumption and blood pressure
      among residents in Shandong province, and to provide basic information for
      guiding people to prevent hypertension by reducing salt intake. METHODS: Using
      multi-stage stratified cluster random sampling method, 2 184 residents aged 18 to
      69 were selected as the research subjects, which were extracted randomly from 20
      counties in Shandong province in June, 2011. The blood pressure of the subjects
      were measured and weighted. Based on 72 h dietary recalls and weighing
      measurement, and according to the distribution of salt intake, the grouping cut
      off points were 10, 14 and 18 g. The difference of subjects with different
      characteristics and systolic blood pressure, diastolic blood pressure and
      prevalence of hypertension by grouping salt intake and other characteristics were
      analyzed, and the relationship between salt intake and prevalence of hypertension
      were analyzed. RESULTS: The total of 2 133 residents were involved finally, the
      completion rate was 97.7%. After the complex weighted, the systolic and diastolic
      blood pressure's means (95%CI value) of the subjects were 121.0 (119.5-122.5)
      mmHg (1 mmHg = 0.133 kPa) and 78.5(77.4-79.6) mmHg respectively, which were all
      elevated with increasing of salt consumption. The blood pressure of the subjects
      with salt intake <10 g was the lowest, which were 119.6 (116.9-122.4) mmHg and
      77.5(76.2-78.7) mmHg respectively. The blood pressure of the subjects with salt
      intake >= 18 g was the highest, which were 122.3(120.1-124.5) mmHg and 79.6(78.2
      80.9) mmHg respectively. The analysis results showed that, among residents with
      normal waistline, the prevalence of hypertension of people with salt intake >= 18
      g was 1.70(95%CI:1.04-2.76) times compared to that of people who consumed less
      than 10 g salt per day. CONCLUSION: The hypertension prevalence of Shandong
      province is quite high, and there is a relationship between salt consumption and
      blood pressure.

PMID- 24746007
TI  - [Analysis on the results of etiology and serology of plague in Qinghai province
      from 2001 to 2010].
AB  - OBJECTIVE: To analyze the results of etiology and serology of plague among human
      and infected animals in Qinghai province from 2001 to 2010. METHODS: Thirty-seven
      cases of human infected with plague, 53 541 different animal samples, 5 685 sets
      of vector insects flea and 49 039 different animal serum samples were obtained
      between 2001 and 2010. A total of 7 811 samples of serum from healthy farmers and
      herdsmen in 14 counties in Qinghai from 2005 to 2007 were collected. Yersinia
      pestis (Y. pestis) were detected in visceral and secretions from human, infected
      animals and vector insects, respectively. Plague antigen was detected by reverse
      indirect hemagglutination assay (RIHA) in those samples. Indirect
      hemagglutination assay (IHA) was used to test plague FI antibody in serum of
      human and infected animals. RESULTS: 37 human plague cases were confirmed, 21
      strains of plague Y. pestis were isolated from human cases and 14 positive were
      detected out. 133 of 7 811 samples of human serum were IHA positive, with the
      positive rate at 1.7%. A total of 146 strains of plague were isolated from
      infected animals and vector insects, 99 out of which were from infected animals,
      with a ratio of Marmota himalayan at 72.7% (72/99) and the other 47 were from
      vector insects, with a ratio of callopsylla solaris at 68.1% (32/47). The number
      of IHA and PIHA positive were 300 and 10, respectively. A total of 3 animals and
      3 insects species were identified as new epidemic hosts for plague. The natural
      plague focus of Microtus fuscus was discovered and confirmed and coexisted with
      natural focus of Marmota himalayan in Chengduo county, Yushu prefecture. The
      epidemic situation of plague is distributed mainly in Haixi, Yushu and Hainan
      prefectures. CONCLUSION: From 2001 to 2010, animal infected with plague was
      detected in successive years and human plague was very common in Qinghai. New
      infected animals and vector insects species and new epidemic areas were
      confirmed, hence the trend of plague prevalence for humans and animals is very
      active in Qinghai province.

PMID- 24746008
TI  - [Factors associated with HIV and syphilis infection among men who have sex with
      men blood donors in Shenzhen].
AB  - OBJECTIVE: To investigate the distribution and factors associated with HIV and
      syphilis infection among Men who have sex with men blood donors (MSMBD) in
      Shenzhen. METHODS: A total of 813 MSMBD were recruited using snowball sampling
      and respondent driven sampling from 2009 to 2012 in Shenzhen. Questionnaire-based
      interviews were conducted on a one-on-one basis. Data were collected including
      socio-demographic information, HIV testing history, self-identified sexual
      orientation, role in homosexual behavior, information about having sex with male
      sexual partners in the past six months and information about having sex with
      female sexual partners in the past six months.5 ml blood samples were taken and
      tested for treponema pallidum and HIV antibodies. Comparisons of syphilis and HIV
      infection among different years were analyzed by the Cochran-Armitage trend test.
      Factors associated with syphilis and HIV infection were analyzed by the
      univariate logistic regression and multivariate unconditional logistic
      regression. RESULTS: The prevalence of syphilis, HIV, and syphilis-HIV co
      infection among 813 participants were 22.0% (179/813), 8.0% (65/813), and 4.2%
      (34/813), respectively. In the multivariate logistic regression analysis, ever
      tested for HIV (versus without HIV testing history, OR (95%CI) = 0.369(0.213
      0.641)) will decrease the risk of HIV infection among MSMBD in comparison with
      never tested for HIV (OR (95%CI) = 0.37 (0.21-0.64) ); having five or more anal
      sexual partners in the past six months and co-infected with syphilis will
      increase the risk of HIV infection among MSMBD in comparison with having 0-1
      sexual partners (OR (95%CI) = 2.04 (1.03-4.06) ) and negative syphilis (OR
      (95%CI) = 4.52(2.64-7.73)), respectively, bisexual orientation, having 2-4 anal
      sexual partners and having five or more anal sexual partners in the past six
      months, using condoms not for every act of anal sex, co-infected with HIV will
      increase the risk of syphilis infection among MSMBD in comparison with homosexual
      orientation (OR (95%CI) = 1.60(1.12-2.27)), having 0-1 sexual partner in the past
      six months (OR (95%CI) = 1.77 (1.09-2.87) and OR (95%CI) = 1.84(1.09-3.08) ) ,
      using condoms for every act of anal sex (OR (95%CI) = 1.61 (1.10-2.36) ) and
      negative HIV (OR (95%CI) = 4.02 (2.33-6.96)), respectively. CONCLUSION: The
      prevalence of HIV and syphilis among MSMBD in Shenzhen are much higher with
      complex influence factors. The relevant government should pay great attention to
      it and ensure the blood safety.

PMID- 24746009
TI  - [The establishment of a novel method of nano-immunomagnetic separation and Real
      time PCR for detecting Vibrio cholerae from seafood].
AB  - OBJECTIVE: A novel method of Nano-Immunomagnetic Separation (Nano-IMS) plus Real
      time PCR was established for detecting Vibrio cholerae. METHODS: The Nano
      Immunomagnetic Beads were created by using the monoclonal antibody of Vibrio
      cholerae, which was named Nano-IMB-Vc. Nano-IMB-Vc has specific adsorption of
      Vibrio cholerae, combined with Real-time PCR technology, a method for rapid
      detection of Vibrio cholerae was established. The capture specificity of Nano-IMB
      Vc was tested by using 15 bacteria strains. The specificity of Real-time PCR
      method was tested by using 102 targets and 101 non-targets bacteria strains. The
      sensitivity of Nano-IMS plus Real-time PCR were tested in pure culture and in
      artificial samples and compared with NMKL No.156. RESULTS: The capture ratio of
      Nano-IMB-Vc was reached 70.2% at the level of 10(3) CFU/ml. In pure culture, the
      sensitivity of Nano-IMS plus Real-time PCR was reached at 5.4*10(2) CFU/ml. The
      specific of Real-time PCR method was tested by using 102 targets and 101 non
      targets bacteria. The results showed that 102 strains of Vibrio cholerae test
      results were all positive, and the rest of the 101 strains of non-target bacteria
      test results were negative. No cross-reaction was founded. Add 1 CFU vibrio
      cholerae per 25 g sample, it could be detect with Nano-IMS plus Real-time PCR
      method after 8 hours enrichment. CONCLUSIONS: The Nano-IMS plus Real-time PCR
      method of Vibrio cholerae established in this study has good specificity and
      sensitivity, which could be applied to the rapid detection of Vibrio cholerae.

PMID- 24746010
TI  - Rivaroxaban in acute coronary syndromes--is it prime time?
AB  - Arterial thrombosis in acute coronary syndrome (ACS) is associated with
      activation of platelets and the coagulation cascade. Persistent thrombin levels
      have been reported after ACS in such patients. Novel oral anticoagulants without
      a need of close monitoring and frequent blood tests such as warfarin can provide
      a chronic beneficial effect on recurrent ischaemic events in such a population.
      Rivaroxaban, a new oral factor Xa inhibitor, has been tried for this indication
      in the 'Anti-Xa Therapy to Lower Cardiovascular Events in Addition to Standard
      Therapy in Subjects With Acute Coronary Syndrome ACS 2-Thrombolysis In Myocardial
      Infarction 51' (ATLAS ACS 2-TIMI 51) trial using a low dose regimen in an attempt
      to balance the adverse effects of bleeding related to chronic anticoagulation on
      background of dual antiplatelet therapy for ACS, and the beneficial effects on
      recurrent coronary ischemia. The role of rivaroxaban in this context has been
      discussed in detail in this review. 

PMID- 24746012
TI  - Molecular diagnosis and species identification of Ehrlichia and Anaplasma
      infections in dogs from Panama, Central America.
AB  - The prevalence and distribution of Anaplasma and Ehrlichia were estimated in 201
      symptomatic dogs from Panama by nested PCR and DNA sequencing of the 16S rRNA
      gene. In total, 163 dogs (70.6%; 163/201) were infected with either Anaplasma or
      Ehrlichia. On the basis of PCR results, the majority of cases were infected with
      E. canis (64.2%; 129/201) followed by 21.4% (43/201) with A. platys, whereas 7.5%
      (15/201) had Anaplasma/Ehrlichia co-infections. Further analyses of 16S rDNA
      partial sequences show sequence homology with E. canis and A. platys from other
      countries. Hematology findings from 79 E. canis PCR-positive dogs included anemia
      (74.7%), thrombocytopenia (81.9%), macroplatelets (29.1%), and leukopenia (6.3%).
      Among 16 A. platys PCR-positive dogs with available hematology, 62.5% were
      anemic, 75% had thrombocytopenia, and 100% had macroplatelets. On the basis of
      E.canis serology (enzyme-linked immunosorbent assay [ELISA]) (n=92 dogs), 30 dogs
      that were seropositive for E. canis were also PCR-positive, whereas among
      seronegatives (n=62), 10 were PCR-positive for E. canis. This study provides the
      first characterization of canine anaplasmosis and ehrlichiosis infections in
      Panama and is important to veterinary public health and comparative studies of
      these pathogens in the Americas.

PMID- 24746011
TI  - Endosomal vesicles as vehicles for viral genomes.
AB  - The endocytic pathway is the principal cell entry pathway for large cargos and
      pathogens. Among the wide variety of specialized lipid structures within
      endosomes, the intraluminal vesicles (ILVs) formed in early endosomes (EEs) and
      transferred to late endosomal compartments are emerging as critical effectors of
      viral infection and immune recognition. Various viruses deliver their genomes
      into these ILVs, which serve as vehicles to transport the genome to the nuclear
      periphery for replication. When secreted as exosomes, ILVs containing viral
      genomes can infect permissive cells or activate immune responses in myeloid
      cells. We therefore propose that endosomal ILVs and exosomes are key effectors of
      viral pathogenesis. 

PMID- 24746013
TI  - PhI(OCOCF3)2-mediated intramolecular oxidative N-N bond formation: metal-free
      synthesis of 1,2,4-triazolo[1,5-a]pyridines.
AB  - The biologically important 1,2,4-triazolo[1,5-a]pyridines were readily
      synthesized from N-(pyridin-2-yl)benzimidamides via phenyliodine
      bis(trifluoroacetate)-mediated intramolecular annulation. This novel strategy
      allows for the convenient construction of a 1,2,4-triazolo[1,5-a]pyridine
      skeleton through direct metal-free oxidative N-N bond formation, featuring a
      short reaction time and high reaction yields. 

PMID- 24746014
TI  - Drug delivery/imaging multifunctionality of mesoporous silica-based composite
      nanostructures.
AB  - INTRODUCTION: Biocompatible mesoporous silica nanoparticles (MSNs) are regarded
      as one of the most promising inorganic drug delivery systems (DDSs) to
      concurrently enhance the therapeutic efficiency and mitigate the side effects of
      anticancer drugs. Elaborately combining multicomponents with MSNs will endow them
      with specific functionalities for cancer therapy and diagnosis, such as targeted
      drug delivery, intelligent on-demand drug releasing, synergistic therapy,
      diagnostic imaging and so on. AREAS COVERED: This review discusses the state-of
      the-art potential obstacles and further perspectives of the chemical
      design/synthesis, in vitro/in vivo pharmaceutical evaluations and potential
      clinical translations of multifunctional mesoporous silica-based nanomaterials
      for biotechnological and biomedical applications, especially against cancer.
      These topics cover the years from 2001 to 2013. EXPERT OPINION: Through the
      comprehensive evaluations of the biosafety and pharmaceutical efficiency,
      elaborately designed/fabricated mesoporous silica-based composite nanoparticles
      show great potentials in clinical applications for efficient diagnostic imaging
      and chemotherapy of cancer.

PMID- 24746015
TI  - Evaluation of EMG, force and joystick as control interfaces for active arm
      supports.
AB  - BACKGROUND: The performance capabilities and limitations of control interfaces
      for the operation of active movement-assistive devices remain unclear. Selecting
      an optimal interface for an application requires a thorough understanding of the
      performance of multiple control interfaces. METHODS: In this study the
      performance of EMG-, force- and joystick-based control interfaces were assessed
      in healthy volunteers with a screen-based one-dimensional position-tracking task.
      The participants had to track a target that was moving according to a multisine
      signal with a bandwidth of 3 Hz. The velocity of the cursor was proportional to
      the interface signal. The performance of the control interfaces were evaluated in
      terms of tracking error, gain margin crossover frequency, information
      transmission rate and effort. RESULTS: None of the evaluated interfaces was
      superior in all four performance descriptors. The EMG-based interface was
      superior in tracking error and gain margin crossover frequency compared to the
      force- and the joystick-based interfaces. The force-based interface provided
      higher information transmission rate and lower effort than the EMG-based
      interface. The joystick-based interface did not present any significant
      difference with the force-based interface for any of the four performance
      descriptors. We found that significant differences in terms of tracking error and
      information transmission rate were present beyond 0.9 and 1.4 Hz respectively.
      CONCLUSIONS: Despite the fact that the EMG-based interface is far from the
      natural way of interacting with the environment, while the force-based interface
      is closer, the EMG-based interface presented very similar and for some
      descriptors even a better performance than the force-based interface for
      frequencies below 1.4 Hz. The classical joystick presented a similar performance
      to the force-based interface and holds the advantage of being a well established
      interface for the control of many assistive devices. From these findings we
      concluded that all the control interfaces considered in this study can be
      regarded as a candidate interface for the control of an active arm support.

PMID- 24746016
TI  - Imaging and tuning molecular levels at the surface of a gated graphene device.
AB  - Gate-controlled tuning of the charge carrier density in graphene devices provides
      new opportunities to control the behavior of molecular adsorbates. We have used
      scanning tunneling microscopy (STM) and spectroscopy (STS) to show how the
      vibronic electronic levels of 1,3,5-tris(2,2-dicyanovinyl)benzene molecules
      adsorbed onto a graphene/BN/SiO2 device can be tuned via application of a
      backgate voltage. The molecules are observed to electronically decouple from the
      graphene layer, giving rise to well-resolved vibronic states in dI/dV
      spectroscopy at the single-molecule level. Density functional theory (DFT) and
      many-body spectral function calculations show that these states arise from
      molecular orbitals coupled strongly to carbon-hydrogen rocking modes. Application
      of a back-gate voltage allows switching between different electronic states of
      the molecules for fixed sample bias. 

PMID- 24746017
TI  - A multiscale 0-D/3-D approach to patient-specific adaptation of a cerebral
      autoregulation model for computational fluid dynamics studies of cardiopulmonary
      bypass.
AB  - Neurological complication often occurs during cardiopulmonary bypass (CPB). One
      of the main causes is hypoperfusion of the cerebral tissue affected by the
      position of the cannula tip and diminished cerebral autoregulation (CA).
      Recently, a lumped parameter approach could describe the baroreflex, one of the
      main mechanisms of cerebral autoregulation, in a computational fluid dynamics
      (CFD) study of CPB. However, the cerebral blood flow (CBF) was overestimated and
      the physiological meaning of the variables and their impact on the model was
      unknown. In this study, we use a 0-D control circuit representation of the
      Baroreflex mechanism, to assess the parameters with respect to their
      physiological meaning and their influence on CBF. Afterwards the parameters are
      transferred to 3D-CFD and the static and dynamic behavior of cerebral
      autoregulation is investigated. The parameters of the baroreflex mechanism can
      reproduce normotensive, hypertensive and impaired autoregulation behavior.
      Further on, the proposed model can mimic the effects of anesthetic agents and
      other factors controlling dynamic CA. The CFD simulations deliver similar results
      of static and dynamic CBF as the 0-D control circuit. This study shows the
      feasibility of a multiscale 0-D/3-D approach to include patient-specific cerebral
      autoregulation into CFD studies. 

PMID- 24746018
TI  - Strain energy in the femoral neck during exercise.
AB  - Physical activity is recommended to mitigate the incidence of hip osteoporotic
      fractures by improving femoral neck strength. However, results from clinical
      studies are highly variable and unclear about the effects of physical activity on
      femoral neck strength. We ranked physical activities recommended for promoting
      bone health based on calculations of strain energy in the femoral neck. According
      to adaptive bone-remodeling theory, bone formation occurs when the strain energy
      (S) exceeds its homeostatic value by 75%. The potential effectiveness of activity
      type was assessed by normalizing strain energy by the applied external load.
      Tensile strain provided an indication of bone fracture. External force and joint
      motion data for 15 low- and high-load weight-bearing and resistance-based
      activities were used. High-load activities included weight-bearing activities
      generating a ground force above 1 body-weight and maximal resistance exercises
      about the hip and the knee. Calculations of femoral loads were based on
      musculoskeletal and finite-element models. Eight of the fifteen activities were
      likely to trigger bone formation, with isokinetic hip extension (DeltaS=722%),
      one-legged long jump (DeltaS=572%), and isokinetic knee flexion (DeltaS=418%)
      inducing the highest strain energy increase. Knee flexion induced approximately
      ten times the normalized strain energy induced by hip adduction. Strain and
      strain energy were strongly correlated with the hip-joint reaction force
      (R(2)=0.90-0.99; p<0.05) for all activities, though the peak load location was
      activity-dependent. None of the exercises was likely to cause fracture. Femoral
      neck mechanics is activity-dependent and maximum isokinetic hip-extension and
      knee-flexion exercises are possible alternative solutions to impact activities
      for improving femoral neck strength. 

PMID- 24746019
TI  - Geometry-based pressure drop prediction in mildly diseased human coronary
      arteries.
AB  - Pressure drop (?p) estimations in human coronary arteries have several important
      applications, including determination of appropriate boundary conditions for CFD
      and estimation of fractional flow reserve (FFR). In this study a ?p prediction
      was made based on geometrical features derived from patient-specific imaging
      data. Twenty-two mildly diseased human coronary arteries were imaged with
      computed tomography and intravascular ultrasound. Each artery was modelled in
      three consecutive steps: from straight to tapered, to stenosed, to curved model.
      CFD was performed to compute the additional ?p in each model under steady flow
      for a wide range of Reynolds numbers. The correlations between the added
      geometrical complexity and additional ?p were used to compute a predicted ?p.
      This predicted ?p based on geometry was compared to CFD results. The mean ?p
      calculated with CFD was 855+/-666Pa. Tapering and curvature added significantly
      to the total ?p, accounting for 31.4+/-19.0% and 18.0+/-10.9% respectively at
      Re=250. Using tapering angle, maximum area stenosis and angularity of the
      centerline, we were able to generate a good estimate for the predicted ?p with a
      low mean but high standard deviation: average error of 41.1+/-287.8Pa at Re=250.
      Furthermore, the predicted ?p was used to accurately estimate FFR (r=0.93). The
      effect of the geometric features was determined and the pressure drop in mildly
      diseased human coronary arteries was predicted quickly based solely on geometry.
      This pressure drop estimation could serve as a boundary condition in CFD to model
      the impact of distal epicardial vessels. 

PMID- 24746020
TI  - Patterns in the knee flexion-extension moment profile during stair ascent and
      descent in patients with total knee arthroplasty.
AB  - The aim of this study was to investigate the prevalence of abnormal knee
      biomechanical patterns in 40 patients with a modern TKA prosthesis, compared to
      40 matched control participants when ascending and descending stairs. Fewer
      patients were able to ascend (65%) or descend stairs (53%) unassisted than
      controls (83%). Of the participants who could ascend and descend, cluster
      analysis classified most patients (up to 77%) as demonstrating a similar knee
      moment pattern as all controls. A small subgroup of patients who completed the
      tasks did so with distinctly abnormal biomechanics compared to other patients and
      controls. These findings suggest that recovery of normal stair climbing is
      possible. However, rehabilitation might be more effective if it were tailored to
      account for these differences between patients. 

PMID- 24746021
TI  - Functional tissue engineering: Ten more years of progress.
AB  - "Functional tissue engineering" is a subset of the field of tissue engineering
      that was proposed by the United States National Committee on Biomechanics over a
      decade ago in order to place more emphasis on the roles of biomechanics and
      mechanobiology in tissue repair and regeneration. Over the past decade, there
      have been tremendous advances in this area, pointing out the critical role that
      biomechanical factors can play in the engineered repair of virtually all tissue
      and organ systems. In this special issue of the Journal of Biomechanics, we
      present a series of articles that address a broad array of the fundamental topics
      of functional tissue engineering, including: (1) measurement and modeling of the
      in vivo biomechanical environment and history in native and repair tissues; (2)
      further understanding of the biomechanical properties of native tissues across
      all geometric scales, in the context of repair or regeneration; (3)
      prioritization of specific biomechanical properties as design criteria; (4)
      development of biomaterials, scaffolds, and engineered tissues with prescribed
      biomechanical properties; (5) development of success criteria based on
      appropriate outcome measures; (6) investigation of the effects of mechanical
      factors on tissue repair in vivo; (7) investigation of the mechanisms by which
      physical factors may enhance tissue regeneration in vitro; and (8) development
      and validation of computational models of tissue growth and remodeling. These
      articles represent the tremendous expansion of this field in recent years, and
      emphasize the critical roles that biomechanics and mechanobiology play in
      controlling tissue repair and regeneration. 

PMID- 24746022
TI  - Kernel density estimation applied to bond length, bond angle, and torsion angle
      distributions.
AB  - We describe the method of kernel density estimation (KDE) and apply it to
      molecular structure data. KDE is a quite general nonparametric statistical method
      suitable even for multimodal data. The method generates smooth probability
      density function (PDF) representations and finds application in diverse fields
      such as signal processing and econometrics. KDE appears to have been under
      utilized as a method in molecular geometry analysis, chemo-informatics, and
      molecular structure optimization. The resulting probability densities have
      advantages over histograms and, importantly, are also suitable for gradient-based
      optimization. To illustrate KDE, we describe its application to chemical bond
      length, bond valence angle, and torsion angle distributions and show the ability
      of the method to model arbitrary torsion angle distributions. 

PMID- 24746023
TI  - Complex chiral colloids and surfaces via high-index off-cut silicon.
AB  - Silicon wafers are commonly etched in potassium hydroxide solutions to form
      highly symmetric surface structures. These arise when slow-etching {111} atomic
      planes are exposed on standard low-index surfaces. However, the ability of
      nonstandard high-index wafers to provide more complex structures by tilting the
      {111} planes has not been fully appreciated. We demonstrate the power of this
      approach by creating chiral surface structures and nanoparticles of a specific
      handedness from gold. When the nanoparticles are dispersed in liquids, gold
      colloids exhibiting record molar circular dichroism (>5 * 10(9) M(-1) cm(-1)) at
      red wavelengths are obtained. The nanoparticles also present chiral pockets for
      binding. 

PMID- 24746024
TI  - Altered spontaneous activity in treatment-naive childhood absence epilepsy
      revealed by Regional Homogeneity.
AB  - PURPOSE: To explore the differences in regional spontaneous activities throughout
      the whole brain by the Regional Homogeneity (ReHo) method in untreated childhood
      absence epilepsy (CAE), in order to understand the neuro-pathophysiological
      mechanism of function impairments in CAE. METHODS: The rest-functional MRI was
      used to measure the ReHo in 16 patients with untreated CAE and 16 age- and sex
      matched healthy controls. The correlations between the ReHo at each voxel of the
      whole brain and duration of epilepsy were analyzed. RESULTS: Compared with
      healthy controls, we found that ReHo was decreased in bilateral thalamus,
      caudate, posterior lobe of cerebellum and areas mainly in the default mode
      network (DMN) (including precuneus and posterior cingulate cortex-PCC, bilateral
      inferior lateral parietal lobule). The increase of ReHo was found in bilateral
      insula, left occipital cortex. Moreover, a correlation analysis of the ReHo
      measurement versus the epilepsy duration was performed, and highly positive
      correlation was observed in precuneus/PCC and supplementary motor area (SMA).
      SIGNIFICANCE: The current findings demonstrated alterations of ReHo in the
      striato-thalamo-cortical network in drug naive CAE subjects during interictal
      resting state. Some regions with decreased ReHo followed the pattern of 'default'
      state of brain function. In addition, positive correlations between the ReHo
      values in the precuneus/PCC and SMA and the disease duration were identified.
      These results indicate that the involvement of these regions may be related to
      the pathomechanisms of seizure generation and the neurological deficits observed
      in CAE patients. ReHo has demonstrated the capability to characterize spontaneous
      brain dysfunction in epilepsy.

PMID- 24746025
TI  - Neonatal capsaicin treatment in rats affects TRPV1-related noxious heat sensation
      and circadian body temperature rhythm.
AB  - The transient receptor potential vanilloid 1 (TRPV1) is a cation channel that
      serves as a polymodal detector of noxious stimuli such as capsaicin. Therefore,
      capsaicin treatment has been used to investigate the physiological function of
      TRPV1. Here, we report physiological changes induced by treating neonatal rats
      with capsaicin. Capsaicin (50mg/kg) (cap-treated) or vehicle (vehicle-treated)
      was systemically administered to newborn SD rat pups within 48 h after birth.
      TRPV1 expression, intake volume of capsaicin water, and noxious heat sensation
      were measured 6 weeks after capsaicin treatment. Circadian body temperature and
      locomotion were recorded by biotelemetry. Expression of Per1, Per2, Bmal1 and
      Hsf1 (clock genes) was also investigated. Neonatal capsaicin treatment not only
      decreased TRPV1 expression but also induced desensitization to noxious heat
      stimuli. Circadian body temperature of cap-treated rats increased significantly
      compared with that of vehicle-treated rats. Additionally, the amplitude of the
      circadian body temperature was reversed in cap-treated rats. Expression of the
      hypothalamic Hsf1 and liver Per2 clock genes followed a similar trend. Therefore,
      we suggest that these findings will be useful in studying various physiological
      mechanisms related to TRPV1.

PMID- 24746026
TI  - Synthesis and characterization of carbazolide-based iridium PNP pincer complexes.
      Mechanistic and computational investigation of alkene hydrogenation: evidence for
      an Ir(III)/Ir(V)/Ir(III) catalytic cycle.
AB  - New carbazolide-based iridium pincer complexes ((carb)PNP)Ir(C2H4), 3a, and
      ((carb)PNP)Ir(H)2, 3b, have been prepared and characterized. The dihydride, 3b,
      reacts with ethylene to yield the cis-dihydride ethylene complex cis
      ((carb)PNP)Ir(C2H4)(H)2. Under ethylene this complex reacts slowly at 70  degrees
      C to yield ethane and the ethylene complex, 3a. Kinetic analysis establishes that
      the reaction rate is dependent on ethylene concentration and labeling studies
      show reversible migratory insertion to form an ethyl hydride complex prior to
      formation of 3a. Exposure of cis-((carb)PNP)Ir(C2H4)(H)2 to hydrogen results in
      very rapid formation of ethane and dihydride, 3b. DFT analysis suggests that
      ethane elimination from the ethyl hydride complex is assisted by ethylene through
      formation of ((carb)PNP)Ir(H)(Et)(C2H4) and by H2 through formation of
      ((carb)PNP)Ir(H)(Et)(H2). Elimination of ethane from Ir(III) complex
      ((carb)PNP)Ir(H)(Et)(H2) is calculated to proceed through an Ir(V) complex
      ((carb)PNP)Ir(H)3(Et) which reductively eliminates ethane with a very low barrier
      to return to the Ir(III) dihydride, 3b. Under catalytic hydrogenation conditions
      (C2H4/H2), cis-((carb)PNP)Ir(C2H4)(H)2 is the catalyst resting state, and the
      catalysis proceeds via an Ir(III)/Ir(V)/Ir(III) cycle. This is in sharp contrast
      to isoelectronic (PCP)Ir systems in which hydrogenation proceeds through an
      Ir(III)/Ir(I)/Ir(III) cycle. The basis for this remarkable difference is
      discussed. 

PMID- 24746028
TI  - Two [1,2,4-(Me3C)3C5H2]2CeH molecules are involved in hydrogenation of pyridine
      to piperidine as shown by experiments and computations.
AB  - Hydrogenation of pyridine to piperidine catalyzed by [1,2,4-(Me3C)3C5H2]2CeH,
      abbreviated as Cp'2CeH or [Ce]'-H, is reported. The reaction proceeds from
      Cp'2Ce(2-pyridyl), isolated from the reaction of pyridine with Cp'2CeH, to
      Cp'2Ce(4,5,6-trihydropyridyl), and then to Cp'2Ce(piperidyl). The cycle is
      completed by the addition of pyridine, which generates Cp'2Ce(2-pyridyl) and
      piperidine. The net reaction depends on the partial pressure of H2 and
      temperature. The dependence of the rate on the H2 pressure is associated with the
      formation of Cp'2CeH, which increases the rate of the first and/or second
      additions of H2 but does not influence the rate of the third addition. Density
      functional theory calculations of several possible pathways are consistent with
      three steps, each of which are composed of two elementary reactions, (i)
      heterolytic activation of H2 with a reasonably high energy, DeltaG(?) = 20.5 kcal
      mol(-1), on Cp'2Ce(2-pyridyl), leading to Cp'2CeH(6-hydropyridyl), followed by an
      intramolecular hydride transfer with a lower activation energy, (ii)
      intermolecular addition of Cp'2CeH to the C(4)?C(5) bond, followed by
      hydrogenolysis, giving Cp'2Ce(4,5,6-trihydropyridyl) and regenerating Cp'2CeH,
      and (iii) a similar hydrogenation/hydrogenolysis sequence, yielding
      Cp'2Ce(piperidyl). The calculations reveal that step ii can only occur in the
      presence of Cp'2CeH and that alternative intramolecular steps have considerably
      higher activation energies. The key point that emerges from these experimental
      and computational studies is that step ii involves two Cp'2Ce fragments, one to
      bind the 6-hydropyridyl ligand and the other to add to the C(4)?C(5) double bond.
      In the presence of H2, this second step is intermolecular and catalytic. The
      cycle is completed by reaction with pyridine to yield Cp'2Ce(2-pyridyl) and
      piperidine. The structures of Cp'2CeX, where X = 2-pyridyl, 4,5,6
      trihydropyridyl, and piperidyl, are fluxional, as shown by variable-temperature
      (1)H NMR spectroscopy. 

PMID- 24746027
TI  - Merkel cells transduce and encode tactile stimuli to drive Abeta-afferent
      impulses.
AB  - Sensory systems for detecting tactile stimuli have evolved from touch-sensing
      nerves in invertebrates to complicated tactile end organs in mammals. Merkel
      discs are tactile end organs consisting of Merkel cells and Abeta-afferent nerve
      endings and are localized in fingertips, whisker hair follicles, and other touch
      sensitive spots. Merkel discs transduce touch into slowly adapting impulses to
      enable tactile discrimination, but their transduction and encoding mechanisms
      remain unknown. Using rat whisker hair follicles, we show that Merkel cells
      rather than Abeta-afferent nerve endings are primary sites of tactile
      transduction and identify the Piezo2 ion channel as the Merkel cell mechanical
      transducer. Piezo2 transduces tactile stimuli into Ca(2+)-action potentials in
      Merkel cells, which drive Abeta-afferent nerve endings to fire slowly adapting
      impulses. We further demonstrate that Piezo2 and Ca(2+)-action potentials in
      Merkel cells are required for behavioral tactile responses. Our findings provide
      insights into how tactile end-organs function and have clinical implications for
      tactile dysfunctions.

PMID- 24746029
TI  - A Rasch analysis of a questionnaire designed to evaluate psychiatric patient
      attitudes and knowledge after attending a pharmacist-led patient medication
      education group.
AB  - BACKGROUND: There are many barriers that prevent persons with mental health
      disorders from achieving remission, including medication nonadherence. Research
      on the impact of pharmacist-led patient medication education groups on patient
      attitudes, knowledge and adherence is limited. OBJECTIVE: To evaluate the
      reliability and validity of the Medication Attitudes and Knowledge Questionnaire
      (MAKQ). METHODS: A retrospective pre-post questionnaire was distributed to
      patients. Variables collected included: patient self-reported medication
      knowledge and attitudes, patient demographics, number of previous psychiatric
      hospitalizations, whether the patient attended the whole meeting or only a
      portion, and outpatient pharmacist relationships. Knowledge and attitude items
      were measured on a 4-point scale with a range of options from "Agree" to
      "Disagree." Rasch analysis was conducted to ensure all items measured the same
      construct and to assess scale and item reliability and validity. Additionally,
      the Rasch technique evaluated the change in each person's self-perceived
      attitudes, knowledge, and confidence in self-managing medications from pre- to
      post-intervention if the data fit the model. A z-test was used to evaluate gaps
      in content validity. RESULTS: Sixty patients responded to the MAKQ over the 16
      week data collection period. Analysis showed that the 4-point rating scale was
      not useful and that negatively worded items should be eliminated. Gaps identified
      in instrument item content were not statistically significant (p > 0.05),
      indicating comprehensive content validity. CONCLUSIONS: Medication attitudes and
      knowledge items on the retrospective pre-post questionnaire were valid and
      reliable.

PMID- 24746030
TI  - Comparison by computed tomographic angiography-the presence and extent of
      coronary arterial atherosclerosis in South Asians versus Caucasians with diabetes
      mellitus.
AB  - South Asians in the Western world have a high prevalence of diabetes mellitus
      (DM) and an increased risk of coronary artery disease (CAD) and mortality
      compared with Caucasians. CAD in asymptomatic South Asian patients with type 2 DM
      has not been investigated. The aim of this observational cohort study was to
      investigate CAD in asymptomatic South Asian patients with type 2 DM and to
      compare with matched Caucasian patients. A total of 120 asymptomatic South Asian
      patients with type 2 DM and matched Caucasian patients (mean age 52 years, 55%
      men) were derived from an ongoing registry of cardiovascular risk stratification
      in asymptomatic patients with DM. Cardiovascular risk assessment included
      multidetector row coronary computed tomography angiography. CAD was assessed as
      the coronary artery calcium score and classified into no signs of atherosclerosis
      or minor wall irregularities <30%, nonsignificant CAD 30% to 50%, or significant
      CAD >=50% stenosis. On a patient base, CAD was scored according to the severity
      and number of vessels and segments with significant CAD. Subsequently, CAD was
      assessed per coronary artery and per segment. Compared with Caucasian patients,
      South Asian patients had a significantly higher coronary artery calcium score and
      higher prevalence of significant CAD (41% vs 28%, respectively, p = 0.008),
      involving more coronary vessels and segments. Significant CAD was especially more
      frequent in the left anterior descending coronary artery. In conclusion,
      asymptomatic South Asian patients with type 2 DM have a higher prevalence and
      extent of CAD compared with matched Caucasian patients.

PMID- 24746031
TI  - Trends in acute myocardial infarction event rates and risk of recurrences after
      an incident event in Norway 1994 to 2009 (from a Cardiovascular Disease in Norway
      Project).
AB  - We explored trends in acute myocardial infarction (AMI) event rates in Norway
      during 1994 to 2009 and trends in the 6-month, 1-year, and 3-year risk of
      recurrences after an incident AMI during 2001 to 2008 in men and women >=25
      years. Trends in AMI event rates (incident and recurrent) were analyzed using
      joinpoint regression analyses and expressed as annual percentage change (APC) in
      rates. Trends in AMI recurrences were explored using conditional risk models for
      ordered events in Cox regression. Analyses were stratified by gender and age
      group. Overall, AMI rates were stable during 1994 to 2002 but declined during
      2002 to 2009 (APC = -2.0; 95% confidence interval [CI] -3.1 to -0.9 in men; APC =
      -2.1; 95% CI -3.8 to -0.5 in women). In the younger age group, rates declined
      during the whole study period in men (APC = -0.6; 95% CI -1.0 to -0.3) but not in
      women. Among older patients, no changes were observed during 1994 to 2002,
      whereas rates declined during 2002 to 2009 (APC = -2.6; 95% CI -3.8 to -1.4 in
      men; APC = -2.4; 95% CI -4.0 to -0.7 in women). During 2001 to 2008, in the older
      age group, the 6-month, 1-year, and 3-year risks of recurrences were reduced
      annually by 4.7%, 4.3%, and 5.4% in men and 5.2%, 5.0%, and 5.7% in women (all
      ptrend <0.001), respectively. No changes were observed in the younger age group.
      In conclusion, favorable trends in AMI event rates and recurrences observed in
      Norway were mostly seen among patients aged 65+ years, whereas less favorable
      trends were observed among younger patients, especially among women.

PMID- 24746032
TI  - The safety of transoral periosteal thyroidectomy: results of Swine models.
AB  - BACKGROUND: Endoscopic thyroid surgery is gaining wide acceptance; however,
      existing endoscopic methods for thyroidectomy have shown several limitations.
      Recently, a transoral technique using video assistance and endoscopy has been
      reported for thyroidectomy. The aim of this study was to define a new technique
      of transoral thyroidectomy using a mandibular periosteal approach to complement
      other types of natural orifice surgery and minimally invasive surgery. MATERIALS
      AND METHODS: Transoral periosteal thyroidectomies were performed in seven living
      pigs to evaluate the feasibility and safety of the new approach. Total
      thyroidectomies were performed in all animals. Follow-up examinations were
      carried out for 7 days and followed by autopsy. RESULTS: Through three trocars in
      the mandibular periosteal area, it was possible to create a working space under
      the platysma muscle and to reach the pretracheal area. Total thyroidectomies were
      also performed via the transoral, mandibular periosteal approach without
      complications in seven orally intubated living pigs. Postoperatively, the white
      blood cell count remained normal in all cases. On the postoperative sacrifice of
      the pigs, three locally encapsulated seromas were observed. Both recurrent
      laryngeal nerves were intact in all cases. CONCLUSIONS: Transoral periosteal
      thyroidectomy could be feasible and safe.

PMID- 24746033
TI  - Unique coral-like image on hysteroscopy.

PMID- 24746034
TI  - Balance failure in single limb stance due to ankle sprain injury: an analysis of
      center of pressure using the fractal dimension method.
AB  - Instrumented postural control analysis plays an important role in evaluating the
      effects of injury on dynamic stability during balance tasks, and is often
      conveyed with measures based on the displacement of the center-of-pressure (COP)
      assessed with a force platform. However, the desired outcome of the task is
      frequently characterized by a loss of dynamic stability, secondary to injury.
      Typically, these failed trials are discarded during research investigations, with
      the potential loss of informative data pertaining to task success. The novelty of
      the present study is that COP characteristics of failed trials in injured
      participants are compared to successful trial data in another injured group, and
      a control group of participants, using the fractal dimension (FD) method. Three
      groups of participants attempted a task of eyes closed single limb stance (SLS):
      twenty-nine participants with acute ankle sprain successfully completed the task
      on their non-injured limb (successful injury group); twenty eight participants
      with acute ankle sprain failed their attempt on their injured limb (failed injury
      group); sixteen participants with no current injury successfully completed the
      task on their non-dominant limb (successful non-injured group). Between trial
      analyses of these groups revealed significant differences in COP trajectory FD
      (successful injury group: 1.58+/-0.06; failed injury group: 1.54+/-0.07;
      successful non-injured group: 1.64+/-0.06) with a large effect size (0.27). These
      findings demonstrate that successful eyes-closed SLS is characterized by a larger
      FD of the COP path when compared to failed trials, and that injury causes a
      decrease in COP path FD. 

PMID- 24746035
TI  - Neurofeedback and physical balance in Parkinson's patients.
AB  - The primary goal of the present research is to study the effect of a
      neurofeedback training (NFT) period on balance problems associated with
      Parkinson's disease. Sixteen patients were selected through purposive sampling
      and were randomly divided into experimental and control groups. The research
      procedure included eight sessions. Prior to and after training, pre-tests and
      post-tests of static and dynamic balance were administered using "limit of
      stability" for the Biodex as well as the Berg scale. The results revealed that,
      after neurofeedback training, a statistically significant improvement in both
      static and dynamic balance in the experimental group was achieved. The means of
      the Biodex and Berg scores in the experimental group increased from 18.87 to
      42.87 and 17.62 to 46.37, respectively. The means of the Biodex and Berg scores
      in the control group in the pretest were 18.25 and 17.75 and increased to 20.00
      and 20.50, respectively. The results suggest that NFT can improve static and
      dynamic balance in PD patients. 

PMID- 24746036
TI  - Advanced oxidation of Reactive Blue 181 solution: a comparison between Fenton and
      Sono-Fenton process.
AB  - In this work, the decolorization of C.I. Reactive Blue 181 (RB181), an
      anthraquinone dye, by Ultrasound and Fe(2+) H2O2 processes was investigated. The
      effects of operating parameters, such as Fe(2+) dosage, H2O2 dosage, pH value,
      reaction time and temperature were examined. Process optimisation [pH, ferrous
      ion (Fe(2+)), hydrogen peroxide (H2O2), and reaction time], kinetic studies and
      their comparison were carried out for both of the processes. The Sono-Fenton
      process was performed by indirect sonication in an ultrasonic water bath, which
      was operated at a fixed 35-kHz frequency. The optimum conditions were determined
      as [Fe(2+)]=30 mg/L, [H2O2]=50 mg/L and pH=3 for the Fenton process and
      [Fe(2+)]=10 mg/L, [H2O2]=40 mg/L and pH=3 for the Sono-Fenton process. The colour
      removals were 88% and 93.5% by the Fenton and Sono-Fenton processes,
      respectively. The highest decolorization was achieved by the Sono-Fenton process
      because of the production of some oxidising agents as a result of sonication. The
      paper also discussed kinetic parameters. The decolorization kinetic of RB181
      followed pseudo-second-order reaction (Fenton study) and Behnajady kinetics (Sono
      Fenton study).

PMID- 24746037
TI  - The effects of hydrogen peroxide on the sonochemical degradation of phenol and
      bisphenol A.
AB  - This report describes the effects of H2O2 concentration (0.01, 0.1, 1, and 10mM)
      on the sonochemical degradation of phenol and bisphenol A (BPA) using an
      ultrasonic source of 35kHz and 0.08W/mL. The concentration of the target
      pollutants (phenol or BPA), total organic carbon (TOC), and H2O2 were monitored
      for each input concentration of H2O2. The effects of H2O2 on the sonochemical
      degradation of phenol was more significant than that of BPA because phenol has a
      high solubility and low octanol-water partition coefficient (Kow) value and is
      subsequently very likely to remain in the aqueous phase, giving it a greater
      probability of reacting with H2O2. The removal of TOC was also enhanced by the
      addition of H2O2. Some intermediates of BPA have a high Kow value and
      subsequently have a greater probability of pyrolyzing by the high temperatures
      and pressures inside of cavitation bubbles. Thus the removal efficiency of TOC in
      BPA was higher than that of phenol. The removal efficiencies of TOC were lower
      than the degradation efficiencies of phenol and BPA. This result is due to the
      fact that some intermediates cannot readily degrade during the sonochemical
      reaction. The H2O2 concentration decreased but was not completely consumed during
      the sonochemical degradation of pollutants. The initial H2O2 concentration and
      the physical/chemical characteristics of pollutants were considered to be
      important factors in determining the formation rate of the H2O2. When high
      concentration of H2O2 was added to the solution, the formation rates were
      relatively low compared to when low concentrations of H2O2 were used. 

PMID- 24746038
TI  - Land use patterns and the risk of West Nile virus transmission in central
      Illinois.
AB  - Understanding how human land use patterns influence mosquito ecology and the risk
      of mosquito-borne pathogens is critical for the development of disease management
      strategies. We examined how different environments influenced mosquito species
      composition, abundance, and West Nile virus (WNV) infection rates in central
      Illinois. Using a combination of gravid traps and CDC light traps, adult
      mosquitoes were collected every other week from June 24 to September 16, 2012, in
      four major land use categories-row crops, prairies, forest fragments, and
      residential neighborhoods. The mosquitoes were identified to species
      morphologically, and pools of pure and mixed Culex mosquitoes (primarily Culex
      pipiens and Culex restuans) were tested for WNV-RNA by qRT-PCR. Mosquito species
      diversity was significantly higher in forest habitats compared to residential,
      agricultural, and prairie land use categories. All the four landscape types were
      equally important habitats for WNV vectors Cx. pipiens and Cx. restuans, contrary
      to previous findings that these species principally inhabit the residential
      areas. WNV-infected mosquito pools were observed in all land use types, and the
      infection rates overlapped among land use categories. Although our findings
      support the importance of residential habitats for WNV transmission to humans,
      they also establish that prairie, row crops, and wood lots are potentially
      important refuges for enzootic transmission. This is particularly important in
      urban ecosystems where these land use categories are small, interspersed
      fragments serving as potential refuge sites during periods of low rainfall.

PMID- 24746039
TI  - Collecting costs of community prevention programs: communities putting prevention
      to work initiative.
AB  - BACKGROUND: Community-based programs require substantial investments of
      resources; however, evaluations of these programs usually lack analyses of
      program costs. Costs of community-based programs reported in previous literature
      are limited and have been estimated retrospectively. PURPOSE: To describe a
      prospective cost data collection approach developed for the Communities Putting
      Prevention to Work (CPPW) program capturing costs for community-based tobacco use
      and obesity prevention strategies. METHODS: A web-based cost data collection
      instrument was developed using an activity-based costing approach. Respondents
      reported quarterly expenditures on labor; consultants; materials, travel, and
      services; overhead; partner efforts; and in-kind contributions. Costs were
      allocated across CPPW objectives and strategies organized around five categories:
      media, access, point of decision/promotion, price, and social support and
      services. The instrument was developed in 2010, quarterly data collections took
      place in 2011-2013, and preliminary analysis was conducted in 2013. RESULTS:
      Preliminary descriptive statistics are presented for the cost data collected from
      51 respondents. More than 50% of program costs were for partner organizations,
      and over 20% of costs were for labor hours. Tobacco communities devoted the
      majority of their efforts to media strategies. Obesity communities spent more
      than half of their resources on access strategies. CONCLUSIONS: Collecting
      accurate cost information on health promotion and disease prevention programs
      presents many challenges. The approach presented in this paper is one of the
      first efforts successfully collecting these types of data and can be replicated
      for collecting costs from other programs.

PMID- 24746040
TI  - Rhythmic bursting in the pre-Botzinger complex: mechanisms and models.
AB  - The pre-Botzinger complex (pre-BotC), a neural structure involved in respiratory
      rhythm generation, can generate rhythmic bursting activity in vitro that persists
      after blockade of synaptic inhibition. Experimental studies have identified two
      mechanisms potentially involved in this activity: one based on the persistent
      sodium current (INaP) and the other involving calcium (ICa) and/or calcium
      activated nonspecific cation (ICAN) currents. In this modeling study, we
      investigated bursting generated in single neurons and excitatory neural
      populations with randomly distributed conductances of INaP and ICa. We analyzed
      the possible roles of these currents, the Na(+)/K(+) pump, synaptic mechanisms,
      and network interactions in rhythmic bursting generated under different
      conditions. We show that a population of synaptically coupled excitatory neurons
      with randomly distributed INaP- and/or ICAN-mediated burst generating mechanisms
      can operate in different oscillatory regimes with bursting dependent on either
      current or independent of both. The existence of multiple oscillatory regimes and
      their state dependence may explain rhythmic activities observed in the pre-BotC
      under different conditions. 

PMID- 24746041
TI  - Effects of glycinergic inhibition failure on respiratory rhythm and pattern
      generation.
AB  - Inhibitory interactions between neurons of the respiratory network are involved
      in rhythm generation and pattern formation. Using a computational model of
      brainstem respiratory networks, we investigated the possible effects of
      suppressing glycinergic inhibition on the activity of different respiratory
      neuron types. Our study revealed that progressive suppression of glycinergic
      inhibition affected all neurons of the network and disturbed neural circuits
      involved in termination of inspiration. Causal was a dysfunction of
      postinspiratory inhibition targeting inspiratory neurons, which often led to
      irregular preterm reactivation of these neurons, producing double or multiple
      short-duration inspiratory bursts. An increasing blockade of glycinergic
      inhibition led to apneustic inspiratory activity. Similar disturbances of
      glycinergic inhibition also occur during hypoxia. A clear difference in prolonged
      hypoxia, however, is that the rhythm terminates in expiratory apnea. The critical
      function of glycinergic inhibition for normal respiratory rhythm generation and
      the consequences of its reduction, including in pathological conditions, are
      discussed. 

PMID- 24746042
TI  - Morphological characterization of respiratory neurons in the pre-Botzinger
      complex.
AB  - Although the pre-Botzinger complex (preBotC) was defined as the inspiratory
      rhythm generator long ago, the functional-anatomical characterization of its
      neuronal components is still being achieved. Recent advances have identified the
      expression of molecular markers in the preBotC neurons that, however, are not
      exclusive to specific respiratory neuron subtypes and have not always been
      related to specific cell morphologies. Here, we evaluated the morphology and the
      axonal projections of electrophysiologically defined respiratory neurons in the
      preBotC using whole-cell recordings and intracellular biocytin labeling. We found
      that respiratory pacemaker neurons are larger than expiratory neurons and that
      inspiratory neurons are smaller than pacemaker and expiratory neurons. Other
      morphological features such as somata shapes or dendritic branching patterns were
      not found to be significantly different among the preBotC neurons sampled. We
      also found that both pacemaker and inspiratory nonpacemaker neurons, but not
      expiratory neurons, show extensive axonal projections to the contralateral
      preBotC and show signs of electrical coupling. Overall, our data suggest that
      there are morphological differences between subtypes of preBotC respiratory
      neurons. It will be important to take such differences in consideration since
      morphological differences would influence synaptic responses and action potential
      propagation. 

PMID- 24746043
TI  - Cytoarchitecture and CO(2) sensitivity of Phox2b-positive Parafacial neurons in
      the newborn rat medulla.
AB  - Preinspiratory (Pre-I) neurons in the parafacial respiratory group (pFRG) compose
      one of the respiratory rhythm generators in the medulla of the newborn rat. It
      has been shown that a subgroup of pFRG/Pre-I neurons could also work as central
      chemoreceptor neurons, because the CO(2) sensitivity of these Pre-I neurons was
      preserved even after blockade of Na(+) channels and Ca(2+) channels, and the
      membrane depolarization induced by hypercapnic stimulation was mainly because of
      the closing of K(+) channels. These neurons, some of which were identified to be
      glutamatergic, express the transcription factor Phox2b. Phox2b expression was one
      of the most noticeable characteristics of pFRG/Pre-I neurons. We also found that
      Phox2b-expressing neurons in the parafacial region of the rostral ventral medulla
      tended to assemble around capillary blood vessels. In contrast, another subclass
      of the pFRG/Pre-I neurons was Phox2b-negative and CO(2)-insensitive. Some of
      these neurons were identified to be glycinergic or GABAergic. Thus, Phox2b
      expression is a key genetic marker that can be used to more clearly establish the
      cell architecture of the pFRG, which consists of heterogeneous neuronal subtypes.
      In this chapter, we elaborate on the CO(2) sensitivity of Phox2b
      positive/negative parafacial neurons and the cytoarchitecture in the newborn rat
      medulla, and discuss ionic mechanisms of CO(2) responsiveness.

PMID- 24746044
TI  - Contributions of the pre-Botzinger complex and the Kolliker-fuse nuclei to
      respiratory rhythm and pattern generation in awake and sleeping goats.
AB  - We investigated in three groups of awake and sleeping goats whether there are
      differences in ventilatory responses after injections of Ibotenic acid (IA,
      glutamate receptor agonist and neurotoxin) into the pre-Botzinger complex
      (preBotC), lateral parabrachial (LPBN), medial (MPBN) parabrachial, or Kolliker
      Fuse nuclei (KFN). In one group, within minutes after bilateral injection of
      10MUl IA (50mM) into the preBotC, there was a 10-fold increase in breathing
      frequency, but 1.5h later, the goats succumbed to terminal apnea. These data are
      consistent with findings in reduced preparations that the preBotC is critical to
      sustaining normal breathing. In a second group, increasing volumes (0.5-10MUl) of
      IA injected at weekly intervals into the preBotC elicited a near-dose-dependent
      tachypnea and irregular breathing that lasted at least 5h. There were apneas
      restricted to wakefulness, but none were terminal. Postmortem histology revealed
      that the preBotC was 90% destroyed, but there was a 25-40% above normal number of
      neurons in the presumed parafacial respiratory group that may have contributed to
      maintenance of arterial blood gas homeostasis. In a third group, bilateral
      injections (1 and 10MUl) of IA into the LPBN, MPBN, or KFN did not significantly
      increase breathing in any group, and there were no terminal apneas. However, 3-5h
      after the injections into the KFN, breathing frequency was decreased and the
      three-phase eupneic breathing pattern was eliminated. Between 10 and 15h after
      the injections, the eupneic breathing pattern was not consistently restored to
      normal, breathing frequency remained attenuated, and there were apneas during
      wakefulness. Our findings during wakefulness and NREM sleep warrant concluding
      that (a) the preBotC is a primary site of respiratory rhythm generation; (b) the
      preBotC and the KFN are determinants of respiratory pattern generation; (c) after
      IA-induced lesions, there is time-dependent plasticity within the respiratory
      control network; and (d) ventilatory control mechanisms are state dependent. 

PMID- 24746046
TI  - Mechanism of sympathetic activation and blood pressure elevation in humans and
      animals following acute intermittent hypoxia.
AB  - Sleep apnea is associated with repeated episodes of hypoxemia, causing marked
      increase in sympathetic nerve activity and blood pressure. Considerable evidence
      suggests that intermittent hypoxia (IH) resulting from apnea is the primary
      stimulus for sympathetic overactivity in sleep apnea patients. Several IH
      protocols have been developed either in animals or in humans to investigate
      mechanisms underlying the altered autonomic regulation of the circulation. Most
      of these protocols involve several days (10-40 days) of IH exposure, that is,
      chronic intermittent hypoxia (CIH). Recent data suggest that a single session of
      IH exposure, that is, acute intermittent hypoxia (AIH), is already capable of
      increasing tonic sympathetic nerve output (sympathetic long-term facilitation,
      LTF) and altering chemo- and baroreflexes with or without elevation of blood
      pressure. This indicates that IH alters the autonomic neurocirculatory at a very
      early time point, although the mechanisms underlying this neuroplasticity have
      not been explored in detail. The purpose of this chapter is to briefly review the
      effects of AIH on sympathetic LTF and alteration of autonomic reflexes in
      comparison with the studies from CIH studies. We will also discuss the potential
      central and peripheral mechanism underlying sympathetic LTF. 

PMID- 24746047
TI  - Effect of chronic intermittent hypoxia on the reflex recruitment of the
      genioglossus during airway obstruction in the anesthetized rat.
AB  - We sought to test the hypothesis that chronic intermittent hypoxia (CIH)-a
      feature of sleep-disordered breathing in humans-impairs reflex recruitment of the
      genioglossus (GG, pharyngeal dilator) during obstructive airway events. Adult
      male Wistar rats were exposed to 20 cycles of normoxia and hypoxia (5% O2 at
      nadir) per hour, 8h a day for 7 days (CIH, N=7). The sham group (N=7) were
      exposed to normoxia in parallel. Following gas treatments, rats were anesthetized
      with an i.p. injection of urethane (1.5g/kg; 20%, w/v). Fine concentric needle
      electrodes were inserted into the GG and the costal diaphragm. Discriminated GG
      motor unit potentials and whole electromyograph (EMG), together with arterial
      blood pressure and arterial O2 saturation, were recorded during quiet basal
      breathing and during nasal airway occlusion. Airway occlusion significantly
      increased GG EMG activity in all animals; but there was no difference in the
      reflex response to airway occlusion between sham and CIH-treated animals (+105+/
      22% vs. +105+/-17%, mean+/-SEM for area under the curve of integrated GG EMG, %
      increase from baseline, p=0.99). Occluded breaths were characterized by a
      significant increase in the firing frequency of phasically active units and the
      recruitment of large motor units that were quiescent under basal conditions.
      Though there are reports of impaired control of the upper airway following CIH in
      the rat, we conclude that reflexly evoked motor discharge to the GG is not
      affected by 7 days of CIH, a paradigm that we have shown increases apnea index in
      sleeping rats. 

PMID- 24746048
TI  - Peptides, serotonin, and breathing: the role of the raphe in the control of
      respiration.
AB  - Over the last 20 years, it has become clear that many functionally defined
      autonomic neurons in the brainstem contain many more than one neurotransmitter.
      Here, the possible role and functions of colocalized neuropeptides in the caudal
      raphe nuclei of the medulla oblongata are discussed. Caudal raphe neurons provide
      an extensive input to neurons throughout the brainstem and spinal cord, including
      respiratory and cardiovascular neurons. It is concluded that one plausible
      function of colocalized neuropeptides is to maintain the membrane potential of
      target neurons within a defined window so that they remain able to function at
      extremes of activity. 

PMID- 24746045
TI  - The integrative role of the sigh in psychology, physiology, pathology, and
      neurobiology.
AB  - "Sighs, tears, grief, distress" expresses Johann Sebastian Bach in a musical
      example for the relationship between sighs and deep emotions. This review
      explores the neurobiological basis of the sigh and its relationship with
      psychology, physiology, and pathology. Sighs monitor changes in brain states,
      induce arousal, and reset breathing variability. These behavioral roles
      homeostatically regulate breathing stability under physiological and pathological
      conditions. Sighs evoked in hypoxia evoke arousal and thereby become critical for
      survival. Hypoarousal and failure to sigh have been associated with sudden infant
      death syndrome. Increased breathing irregularity may provoke excessive sighing
      and hyperarousal, a behavioral sequence that may play a role in panic disorders.
      Essential for generating sighs and breathing is the pre-Botzinger complex.
      Modulatory and synaptic interactions within this local network and between
      networks located in the brainstem, cerebellum, cortex, hypothalamus, amygdala,
      and the periaqueductal gray may govern the relationships between physiology,
      psychology, and pathology. Unraveling these circuits will lead to a better
      understanding of how we balance emotions and how emotions become pathological. 

PMID- 24746049
TI  - Cardiorespiratory coupling: common rhythms in cardiac, sympathetic, and
      respiratory activities.
AB  - Cardiorespiratory coupling is an encompassing term describing more than the well
      recognized influences of respiration on heart rate and blood pressure. Our data
      indicate that cardiorespiratory coupling reflects a reciprocal interaction
      between autonomic and respiratory control systems, and the cardiovascular system
      modulates the ventilatory pattern as well. For example, cardioventilatory
      coupling refers to the influence of heart beats and arterial pulse pressure on
      respiration and is the tendency for the next inspiration to start at a preferred
      latency after the last heart beat in expiration. Multiple complementary, well
      described mechanisms mediate respiration's influence on cardiovascular function,
      whereas mechanisms mediating the cardiovascular system's influence on respiration
      may only be through the baroreceptors but are just being identified. Our review
      will describe a differential effect of conditioning rats with either chronic
      intermittent or sustained hypoxia on sympathetic nerve activity but also on
      ventilatory pattern variability. Both intermittent and sustained hypoxia increase
      sympathetic nerve activity after 2 weeks but affect sympatho-respiratory coupling
      differentially. Intermittent hypoxia enhances sympatho-respiratory coupling,
      which is associated with low variability in the ventilatory pattern. In contrast,
      after constant hypobaric hypoxia, 1-to-1 coupling between bursts of sympathetic
      and phrenic nerve activity is replaced by 2-to-3 coupling. This change in
      coupling pattern is associated with increased variability of the ventilatory
      pattern. After baro-denervating hypobaric hypoxic-conditioned rats, splanchnic
      sympathetic nerve activity becomes tonic (distinct bursts are absent) with
      decreases during phrenic nerve bursts and ventilatory pattern becomes regular.
      Thus, conditioning rats to either intermittent or sustained hypoxia accentuates
      the reciprocal nature of cardiorespiratory coupling. Finally, identifying a
      compelling physiologic purpose for cardiorespiratory coupling is the biggest
      barrier for recognizing its significance. Cardiorespiratory coupling has only a
      small effect on the efficiency of gas exchange; rather, we propose that
      cardiorespiratory control system may act as weakly coupled oscillator to maintain
      rhythms within a bounded variability. 

PMID- 24746050
TI  - Serotonin neurons and central respiratory chemoreception: where are we now?
AB  - Serotonin (5-hydroxytryptamine, 5-HT) neurons are widely considered to play an
      important role in central respiratory chemoreception. Although many studies in
      the past decades have supported this hypothesis, there had been concerns about
      its validity until recently. One recurring claim had been that 5-HT neurons are
      not consistently sensitive to hypercapnia in vivo. Another belief was that 5-HT
      neurons do not stimulate breathing; instead, they inhibit or modulate respiratory
      output. It was also believed by some that 5-HT neuron chemosensitivity is
      dependent on TASK channels, but mice with genetic deletion of TASK-1 and TASK-3
      have a normal hypercapnic ventilatory response. This review explains why these
      principal arguments against the hypothesis are not supported by existing data.
      Despite repeated challenges, a large body of evidence now supports the conclusion
      that at least a subset of 5-HT neurons are central chemoreceptors. 

PMID- 24746051
TI  - Bidirectional plasticity of pontine pneumotaxic postinspiratory drive:
      implication for a pontomedullary respiratory central pattern generator.
AB  - The "pneumotaxic center" in the rostral dorsolateral pons as delineated by
      Lumsden nine decades ago is known to play an important role in promoting the
      inspiratory off-switch (IOS) for inspiratory-expiratory phase transition as a
      fail-safe mechanism for preventing apneusis in the absence of vagal input.
      Traditionally, the pontine pneumotaxic mechanism has been thought to contribute a
      tonic descending input that lowers the IOS threshold in medullary respiratory
      central pattern generator (rCPG) circuits, but otherwise does not constitute part
      of the rCPG. Recent evidence indicates that descending input from the Kolliker
      Fuse nucleus (KFN) within the pneumotaxic center is essential for gating the
      postinspiratory phase of the three-phase respiratory rhythm to control the IOS in
      vagotomized animals. A critical question arising is whether such a descending
      pneumotaxic input from KFN that drives postinspiratory activity is tonic (null
      hypothesis) or rhythmic with postinspiratory phase modulation (alternative
      hypothesis). Here, we show that multifarious evidence reported in the literature
      collectively indicates that the descending pneumotaxic input may exhibit NMDA
      receptor-dependent short-term plasticity in the form of a biphasic neural
      differentiator that bidirectionally and phase-selectively modulates
      postinspiratory phase duration in response to vagal and peripheral chemoreceptor
      inputs independent of the responses in inspiratory and late-expiratory
      activities. The phase-selectivity property of the descending pneumotaxic input
      implicates a population of pontine early-expiratory (postinspiratory/expiratory
      decrementing) neurons as the most likely neural correlate of the pneumotaxic
      mechanism that drives post-I activity, suggesting that the pontine pneumotaxic
      mechanism may be an integral part of a pontomedullary rCPG that underlies the
      three-phase respiratory rhythm. 

PMID- 24746052
TI  - Sleep-wake control of the upper airway by noradrenergic neurons, with and without
      intermittent hypoxia.
AB  - Hypoglossal (XII) motoneurons innervate muscles of the tongue whose tonic and
      inspiratory modulated activity protects the upper airway from collapse in
      patients affected by the obstructive sleep apnea (OSA) syndrome. Both
      norepinephrine and serotonin provide wakefulness-related excitatory drives that
      maintain activity in XII motoneurons, with the noradrenergic system playing a
      particularly prominent role in rats. When noradrenergic and serotonergic drives
      are antagonized, no further decline of XII nerve activity occurs during
      pharmacologically induced rapid eye movement (REM) sleep-like state. This is the
      best evidence to date that, at least in this model, the entire REM sleep-related
      decline of upper airway muscle tone results from withdrawal of these two
      excitatory inputs. A major component of noradrenergic input to XII motoneurons
      originates from pontine noradrenergic neurons that have state-dependent patterns
      of activity, maximal during wakefulness, and minimal, or absent during REM sleep.
      Our data suggest that not all ventrolateral medullary catecholaminergic neurons
      follow this pattern, with adrenergic C1 neurons probably increasing their
      activity during REM sleep. When rats are subjected to chronic-intermittent
      hypoxia, noradrenergic drive to XII motoneurons is increased by mechanisms that
      include sprouting of noradrenergic terminals in the XII nucleus, and increased
      expression of alpha1-adrenoceptors; an outcome that may underlie the elevated
      baseline activity of upper airway muscles during wakefulness in OSA patients. 

PMID- 24746054
TI  - The neural control of human inspiratory muscles.
AB  - The neural control of inspiratory muscles can be assessed in human subjects by
      measurement of the behavior of populations of single motor unit from the various
      inspiratory muscles. The discharge frequencies and patterns of firing of the
      motor units directly reflect the output of the motoneurons that innervate them.
      With the use of these methods, our work has revealed several features of the way
      the output of different inspiratory motoneuron pools are controlled. The output
      of inspiratory motoneurons is nonuniform across pools during quiet breathing and
      this coordinates the contraction of all the different muscles. This output is
      geared to the mechanical advantage of the muscles that they innervate. For the
      intercostal muscles, there is recruitment of the motor units by a principle of
      neuromechanical matching in which neural drive is higher in the muscles with the
      greatest mechanical advantage for inspiration, presumably to minimize the
      metabolic cost of ventilation. We summarize some evidence that this principle is
      likely to be organized at the spinal cord, although the exact underlying
      mechanisms are not known. The specific differences in the output from
      motoneurones innervating parasternal intercostal and diaphragm muscles during
      trunk rotation suggest that the output of inspiratory motoneurones engaged in a
      nonrespiratory voluntary task involve integration of corticospinal and
      bulbospinal drives at the spinal cord. An evolutionary argument is presented to
      support the importance of a role for spinal integration in ventilatory control. 

PMID- 24746053
TI  - Affective brain areas and sleep-disordered breathing.
AB  - The neural damage accompanying the hypoxia, reduced perfusion, and other
      consequences of sleep-disordered breathing, found in obstructive sleep apnea,
      heart failure, and congenital central hypoventilation syndrome (CCHS), appears in
      areas that serve multiple functions, including emotional drives to breathe, and
      involve systems that serve affective, cardiovascular, and breathing roles. The
      damage, assessed with structural magnetic resonance imaging (MRI) procedures,
      shows tissue loss or water content and diffusion changes indicative of injury,
      and impaired axonal integrity between structures; damage is preferentially
      unilateral. Functional MRI responses in affected areas also are time- or
      amplitude-distorted to ventilatory or autonomic challenges. Among the structures
      injured are the insular, cingulate, and ventral medial prefrontal cortices, as
      well as cerebellar deep nuclei and cortex, anterior hypothalamus, caudal raphe,
      ventrolateral medulla, portions of the basal ganglia and, in CCHS, the locus
      coeruleus. Caudal raphe and locus coeruleus injury have the potential to modify
      serotonergic and adrenergic modulation of upper airway and arousal
      characteristics, as well as affective drive to breathe. Since both axons and gray
      matter show injury, the consequences to function, especially to autonomic,
      cognitive, and mood regulation, are major. Several of the affected rostral sites
      mediate aspects of dyspnea, especially in CCHS, while others participate in
      initiation of inspiration after central breathing pauses, and the medullary
      injury can impair baroreflex and breathing control. The ancillary injury
      associated with sleep-disordered breathing to central structures can elicit
      multiple other distortions in cardiovascular, cognitive, and emotional functions
      in addition to effects on breathing regulation. 

PMID- 24746056
TI  - The peripheral actions of the central neuropeptide somatostatin on control of
      breathing: effect on metabolic rate and chemoreflex responses in humans.
AB  - Peripherally infused somatostatin in humans reduces the acute ventilatory
      response to hypoxia but it is not known if it reduces basal minute ventilation,
      and there are conflicting results as to whether or not it reduces the acute
      hypercapnic ventilatory response. One explanatory mechanism for all these
      possible effects is that somatostatin reduces metabolic rate. We therefore tested
      the hypothesis that somatostatin can reduce whole-body metabolic rate (measured
      by gas exchange at the mouth) in a manner that (a) reduces basal minute
      ventilation, (b) reduces ventilatory response to acute hypoxia, and (c) reduces
      ventilatory response to acute hypercapnia. Seven healthy volunteers underwent two
      protocols, one with saline control and one with somatostatin infusion (0.5mg/h)
      consisting of a 15-min period of resting breathing (end-tidal [Formula: see text]
      held at 100Torr with background isocapnia) followed by 5min of isocapnic hypoxia
      (end-tidal [Formula: see text] 50Torr), and after 1min euoxic recovery, 5min of
      euoxic hypercapnia (end-tidal [Formula: see text] 45Torr), followed by recovery.
      Somatostatin modestly but significantly (p<0.05) reduced CO2 output, but not O2
      uptake. However, somatostatin did not change basal minute ventilation. Acute
      hypoxic ventilatory response was greatly reduced by 82% and acute hypercapnic
      ventilatory response by 26% (p<0.05). We conclude that while somatostatin does
      influence metabolism, this effect is too subtle to explain the large reduction in
      chemoreflex activity, which is more likely due to direct effects of the drug on
      the carotid body. 

PMID- 24746057
TI  - Control of the lungs via the human brain using neurosurgery.
AB  - Neurosurgery can alter cardiorespiratory performance via central networks and
      includes deep brain stimulation (DBS), a routinely employed therapy for movement
      disorders and chronic pain syndromes. We review the established cardiovascular
      effects of DBS and the presumed mechanism by which they are produced via the
      central autonomic network. We then review the respiratory effects of DBS,
      including modulation of respiratory rate and lung function indices, and the
      mechanisms via which these may occur. We conclude by highlighting the potential
      future therapeutic applications of DBS for intractable airway diseases. 

PMID- 24746055
TI  - Convergence of pattern generator outputs on a common mechanism of diaphragm motor
      unit recruitment.
AB  - Motor units are the final element of neuromotor control. In manner analogous to
      the organization of neuromotor control in other skeletal muscles, diaphragm motor
      units comprise phrenic motoneurons located in the cervical spinal cord that
      innervate the diaphragm muscle, the main inspiratory muscle in mammals. Diaphragm
      motor units play a primary role in sustaining ventilation but are also active in
      other nonventilatory behaviors, including coughing, sneezing, vomiting,
      defecation, and parturition. Diaphragm muscle fibers comprise all fiber types.
      Thus, diaphragm motor units display substantial differences in contractile and
      fatigue properties, but importantly, properties of the motoneuron and muscle
      fibers within a motor unit are matched. As in other skeletal muscles, diaphragm
      motor units are recruited in order such that motor units that display greater
      fatigue resistance are recruited earlier and more often than more fatigable motor
      units. The properties of the motor unit population are critical determinants of
      the function of a skeletal muscle across the range of possible motor tasks.
      Accordingly, fatigue-resistant motor units are sufficient to generate the forces
      necessary for ventilatory behaviors, whereas more fatigable units are only
      activated during expulsive behaviors important for airway clearance. Neuromotor
      control of diaphragm motor units may reflect selective inputs from distinct
      pattern generators distributed according to the motor unit properties necessary
      to accomplish these different motor tasks. In contrast, widely distributed inputs
      to phrenic motoneurons from various pattern generators (e.g., for breathing,
      coughing, or vocalization) would dictate recruitment order based on intrinsic
      electrophysiological properties. 

PMID- 24746058
TI  - Where is the rhythm generator for emotional breathing?
AB  - As a result of recent progress in brain imaging techniques, a number of studies
      have been able to identify anatomical correlates of various emotions (Pujol et
      al., 2013; Tettamanti et al., 2012; van der Zwaag et al., 2012). However,
      emotions are not solely a phenomenon within the brain-they are also composed of
      body responses. These include autonomic and behavioral responses, such as changes
      in heart rate, blood pressure, skin conductance, and respiration. Among these
      physiological responses, respiration has a unique relationship to emotion. While
      the primary role of respiration concerns metabolism and homeostasis, emotions
      such as disgust, anger, and happiness also influence respiratory activities
      (Boiten et al., 1994). While respiratory change that accompanies emotions can
      occur unconsciously, respiration can also be voluntarily altered associating with
      an activation of the motor cortex. There may be no physiological expression for
      the association between the three areas of the brain that regulate respiration:
      the brainstem, the limbic system, and the cerebral cortex. The brainstem works to
      maintain homeostasis, the limbic system is responsible for emotional processing,
      and the cerebral cortex controls intention. Investigating the interaction between
      these brain regions may lead to an explanation about why they are so widely
      dispersed in the brain, despite their common role in the regulation of
      respiration. In this chapter, we review our findings on breathing behavior and
      discuss the mechanisms underlying the relationship between emotion and
      respiration. 

PMID- 24746059
TI  - The periaqueductal gray controls brainstem emotional motor systems including
      respiration.
AB  - Respiration is a motor system essential for the survival of the individual and of
      the species. Because of its vital significance, studies on respiration often
      assume that breathing takes place independent of other motor systems. However,
      motor systems generating vocalization, coughing, sneezing, vomiting, as well as
      parturition, ejaculation, and defecation encompass abdominal pressure control,
      which involves changes in the respiratory pattern. The mesencephalic
      periaqueductal gray (PAG) controls all these motor systems. It determines the
      level setting of the whole body by means of its very strong projections to the
      ventromedial medullary tegmentum, but it also controls the cell groups that
      generate vocalization, coughing, sneezing, vomiting, as well as respiration. For
      this control, the PAG maintains very strong connections with the nucleus
      retroambiguus, which enables it to control abdominal and intrathoracic pressure.
      In this same context, the PAG also runs the pelvic organs, bladder, uterus,
      prostate, seminal vesicles, and the distal colon and rectum via its projections
      to the pelvic organ stimulating center and the pelvic floor stimulating center.
      These cell groups, via long descending projections, have direct control of the
      parasympathetic motoneurons in the sacral cord as well as of the somatic
      motoneurons in the nucleus of Onuf, innervating the pelvic floor. Respiration,
      therefore, is not a motor system that functions by itself, but is strongly
      regulated by the same systems that also control the other motor output systems. 

PMID- 24746060
TI  - Preface. At the meeting of the Society for Neuroscience in 2009.

PMID- 24746061
TI  - Heart failure with preserved ejection fraction.
AB  - Heart failure with preserved ejection fraction accounts for up to 50% of
      hospitalized heart failure patients and is associated with significant mortality
      and morbidity. The pathophysiology is heterogeneous and not very well defined,
      which explains the lack of disease-specific therapies. The principles of treating
      heart failure with preserved ejection fraction are controlling volume with
      diuretics and diet, and controlling the comorbidities, mainly the hypertension.
      Further research is encouraged to ascertain the key components of the disease
      that will serve as targets for therapy. 

PMID- 24746062
TI  - Atomically resolved graphitic surfaces in air by atomic force microscopy.
AB  - Imaging at the atomic scale using atomic force microscopy in biocompatible
      environments is an ongoing challenge. We demonstrate atomic resolution of
      graphite and hydrogen-intercalated graphene on SiC in air. The main challenges
      arise from the overall surface cleanliness and the water layers which form on
      almost all surfaces. To further investigate the influence of the water layers, we
      compare data taken with a hydrophilic bulk-silicon tip to a hydrophobic bulk
      sapphire tip. While atomic resolution can be achieved with both tip materials at
      moderate interaction forces, there are strong differences in force versus
      distance spectra which relate to the water layers on the tips and samples.
      Imaging at very low tip-sample interaction forces results in the observation of
      large terraces of a naturally occurring stripe structure on the hydrogen
      intercalated graphene. This structure has been previously reported on graphitic
      surfaces that are not covered with disordered adsorbates in ambient conditions
      (i.e., on graphite and bilayer graphene on SiC, but not on monolayer graphene on
      SiC). Both these observations indicate that hydrogen-intercalated graphene is
      close to an ideal graphene sample in ambient environments. 

PMID- 24746063
TI  - Sildenafil citrate as oral solid lipid nanoparticles: a novel formula with higher
      bioavailability and sustained action for treatment of erectile dysfunction.
AB  - OBJECTIVE: The aim of this study was to prepare sildenafil citrate as solid lipid
      nanoparticles (SLNs), in order to find an innovative way for alleviating the
      disadvantages associated with commercially available sildenafil citrate tablets.
      These limitations include poor solubility and extensive first-pass metabolism,
      resulting in low (40%) bioavailability and short elimination half-life (4 h).
      METHODS: SLNs were prepared by hot homogenization followed by ultrasonication.
      Solubility of sildenafil citrate in different solid lipids was measured, effect
      of process variables as surfactant type and concentration, homogenization time,
      ultrasonication time and charge-inducing agent on the particle size, zeta
      potential and encapsulation efficiency were also determined. Furthermore, in
      vitro drug release, stability and in vivo pharmacokinetics were studied in
      rabbits Results: The best SLN formula consisted of 2% precirol ATO5, 0.5%
      phosphatidylcholine, 2.5% gelucire 44/14, 0.125% stearylamine, had an average
      particle size of 28.5 nm with 95.34% entrapment efficiency and demonstrated a
      controlled drug release over 24 h. An in vivo pharmacokinetic study revealed
      enhanced bioavailability by > 1.87 fold, and the mean residence time was longer
      than that for the commercially available tablet. CONCLUSION: SLN could be a
      promising carrier for sustained/prolonged sildenafil citrate release with
      enhanced oral bioavailability.

PMID- 24746067
TI  - Transition metal-free cascade reactions of alkynols to afford isoquinolin-1(2H)
      one and dihydroisobenzofuran derivatives.
AB  - Transition metal-free cascade reactions of alkynols with imines have been
      achieved using potassium tert-butoxide as catalyst. Switching the reaction
      solvent gives two kinds of products in good yield: isoquinolin-1(2H)-one
      derivatives and dihydroisobenzofuran derivatives. This approach was used to
      generate the natural product 8-oxypseudopalmatine in a two-step procedure from
      commercially available starting materials. Additionally, multicomponent reactions
      of alkynols, aldehydes, and amines were also successfully achieved to afford
      isoquinolin-1(2H)-one derivatives. 

PMID- 24746068
TI  - iPod-based in-home system for monitoring gaze-stabilization exercise compliance
      of individuals with vestibular hypofunction.
AB  - BACKGROUND: In the physical therapy setting, physical therapists (PTs) often
      prescribe exercises for their clients to perform at home. However, it is
      difficult for PTs to obtain information about their clients' compliance with the
      prescribed exercises, the quality of performance and symptom magnitude. We
      present an iPod-based system for capturing this information from individuals with
      vestibular hypofunction while they perform gaze stabilization exercises at home.
      METHOD: The system's accuracy for measurement of rotational velocity against an
      independent motion tracker was validated. Then a seven day in-home trial was
      conducted with 10 individuals to assess the feasibility of implementing the
      system. Compliance was measured by comparing the recorded frequency and duration
      of the exercises with the exercise prescription. The velocity and range of motion
      of head movements was recorded in the pitch and yaw planes. The system also
      recorded dizziness severity before and after each exercise was performed. Each
      patient was interviewed briefly after the trial to ascertain ease of use. In
      addition, an interview was performed with PTs in order to assess how the
      information would be utilized. RESULTS: The correlation of the velocity
      measurements between the iPod-based system and the motion tracker was 0.99. Half
      of the subjects were under-compliant with the prescribed exercises. The average
      head velocity during performance was 140 deg/s in the yaw plane and 101 deg/s in
      the pitch plane. CONCLUSIONS: The iPod-based system was able to be used in-home.
      Interviews with PTs suggest that the quantitative data from the system will be
      valuable for assisting PTs in understanding exercise performance of patients,
      documenting progress, making treatment decisions, and communicating patient
      status to other PTs.

PMID- 24746069
TI  - Determination of fungicides in white grape bagasse by pressurized liquid
      extraction and gas chromatography tandem mass spectrometry.
AB  - Ultrasound-assisted extraction (UAE) and pressurized liquid extraction (PLE)
      followed by gas chromatography-triple quadrupole-mass spectrometry (GC TQ-MS)
      were used for the rapid determination of 11 fungicides (metalaxyl, cyprodinil,
      procymidone, iprovalicarb, myclobutanyl, kresoxim-methyl, benalaxyl, fenhexamide,
      tebuconazole, iprodione and dimethomorph) in white grape bagasse. The extractions
      were optimized on real non-spiked samples by means of experimental design and the
      optimal conditions were selected to achieve the method validation. The PLE
      procedure showed much higher efficiency than UAE for the target fungicides. Under
      the selected extraction conditions, PLE showed satisfactory linearity,
      repeatability and reproducibility. Recoveries for the majority of studied
      fungicides were higher than 80% with relative standard deviations (RSD) lower
      than 12%. Limits of detection (LODs) for GC TQ-MS were very low, at the sub ngg(
      1) for the majority of the target fungicides, well below the European maximum
      residue limits (MRLs) for wine and table grapes, and vine leaves. Eighteen white
      grape bagasse samples were analyzed and nine out of eleven targets were detected
      in the samples. Seven of them were detected in more than 50% of the samples and
      most samples contained at least four of the target analytes. The most frequently
      found compounds were tebuconazole and dimethomorph with concentrations between
      1.6-130 and 2.0-1788ngg(-1), respectively. Some samples showed high levels of
      many of the studied fungicides (high ngg(-1), even MUgg(-1) for cyprodinil,
      fenhexamide, iprodione and dimethomorph), but all of them below the European
      maximum residue limits (MRLs) for wine grapes. 

PMID- 24746070
TI  - Multiclass analysis of mycotoxins in biscuits by high performance liquid
      chromatography-tandem mass spectrometry. Comparison of different extraction
      procedures.
AB  - A sensitive, simple and rapid method for the simultaneous determination of 19
      mycotoxins in biscuits (a dry matrix containing cereals and egg) has been
      developed using high performance liquid chromatography coupled to tandem mass
      spectrometry with electrospray source working in both positive and negative mode.
      Due to the matrix complexity and the high amount of contaminants, a solid phase
      extraction method using graphitized carbon black was optimized for an effective
      clean-up step. Accuracy was carried out in the selected matrix using blank
      samples spiked at three analyte concentrations. Recoveries between 63 and 107%
      and relative standard deviations lower than 12% were obtained. For all considered
      mycotoxin classes, i.e. thricotecenes A and B, zearalenone and its metabolites,
      fumonisins, ochratoxin A, enniatins and their structurally related beauvericin,
      the method was validated in terms of linearity, recovery, matrix effect,
      precision, limit of detection and limit of quantification. Matrix-matched
      calibration was used for quantification purposes, in order to compensate for
      matrix effect. The coefficients of determination obtained were in the range of
      0.9927-1. The limits of quantification, ranging from 0.04MUgkg(-1) for enniatin
      B1 to 80.2MUgkg(-1) for nivalenol, were always lower than maximum permitted
      levels for every regulated mycotoxin by the current European legislation. 

PMID- 24746071
TI  - [Ventilator-associated pneumonia: from guideline to practice].

PMID- 24746072
TI  - [Management and prevention of VAP:epidemiology is the key].

PMID- 24746074
TI  - [How to understand the diagnosis of VAP correctly].

PMID- 24746073
TI  - [Ventilator-associated pneumonia :prevention is very important].

PMID- 24746075
TI  - [Treatment of VAP: how to implement empirical treatment].

PMID- 24746076
TI  - [Interpretation of Chinese guideline of ventilator associated pneumonia 2013].

PMID- 24746077
TI  - [Application of GRADE method in evidence: based clinical practice guidelines for
      ventilator associated pneumonia].

PMID- 24746078
TI  - [Effects of different transfusion on intraoperative blood loss and postoperative
      drainage volume in posterior lumbar spinal surgery].
AB  - OBJECTIVE: To explore the effects of autotransfusion on intraoperative blood loss
      and postoperative drainage volume in posterior lumbar spinal surgery. METHODS:
      From June 2010 to January 2012, a total of 183 patients with lumbar disease were
      enrolled. There were 74 males and 109 females with an average age of 56.6 (31-81)
      years. There were lumbar disc herniation (n = 80), lumbar stenosis (n = 69),
      lumbar spondylolisthesis (n = 32) and discogenic pain (n = 2). And one-level (n =
      83) and two-level (n = 100) operations were performed. The treatments were non
      transfusion (n = 34), auto-blood (n = 109) and allogeneic blood (n = 20) and both
      (n = 20).Operative duration, operative level, intraoperative autologous blood
      transfusion, intraoperative allogeneic blood transfusion, intraoperative blood
      loss, immediate drainage volume, duration of drainage tube and final drainage
      volume were recorded. RESULTS: The mean intraoperative blood loss was (369.4 +/-
      284.0) ml and (568.8 +/- 398.7) ml for two-level operation, there were
      significant differences between them(t = 3.94, P < 0.001). The final drainage
      volume was (186.3 +/- 135.6) ml for one-level patients and (301.4 +/- 286.8) ml
      for two-level patients, there were significant differences between them (t =
      3.56, P < 0.05). The total intraoperative blood loss was (478.3 +/- 364.3) ml and
      total final drainage volume was (249.2 +/- 237.4) ml, there were significant
      differences between them(P < 0.001). There were significant differences in blood
      loss between autologous blood transfusion for non-transfusion groups (P < 0.001)
      .However, there was no difference for immediate drainage and final drainage
      comparing with other blood transfusion methods (P > 0.05) . CONCLUSION: Using
      autologous blood transfusion alone during operation has significant difference
      for inoperative blood loss compared with non-transfusion. Yet there is no effect
      on immediate or final drainage volume.

PMID- 24746079
TI  - [Endovascular treatment of ruptured abdominal aortic aneurysm a clinical analysis
      of 13 cases].
AB  - OBJECTIVE: To evaluate the effect of endovascular aneurysm repair(EVAR) of
      ruptured abdominal aortic aneurysm(rAAA) and to summarize the experience.
      METHODS: The clinical data of 13 RAAA cases(males 11, females 2, age range 69-88)
      undergoing EVAR from February 2002 to February 2013 were retrospectively
      analyzed.It consisted of 10 atherosclerotic aneurysms and 3 pseudoaneurysms. CTA
      was finished in all of them. And they all undergone emergency surgery. RESULTS:
      All of the cases were successfully treated. During the perioperation , one
      suffered from contrast induced nephropathy and there were no deaths. During the
      follow-up, there were one case of type Ia endoleak treated by embolism and one
      case of rerupture pseudoaneurysm which abandoned treatment. CONCLUSION:
      Endovascular repair is the safe and effective treatment for ruptured abdominal
      aortic aneurysm.

PMID- 24746080
TI  - [Treatment strategies of inflammatory abdominal aortic aneurysm].
AB  - OBJECTIVE: Summarizes the treatment effect of inflammatory abdominal aortic
      aneurysm (inflammatory abdominal aortic aneurysm, IAAA), and explore its
      therapeutic strategy. METHODS: Retrospectively analysis 17 cases of IAAA in our
      center from January 2002 to August 2012, 16 males, 1 female, mean age 52-79 (67
      +/- 8). 4 cases were treated by conservative medical treatment, 5 cases treated
      by open surgery, 8 cases treated by EVAR. RESULTS: During follow-up no aneurysm
      related death. Follow-up for the conservative medical treatment group was a mean
      of (10 +/- 6) months, 1 case transit to EVAR, the aneurysm diameter of 2 cases
      decreased 2 mm and 4 mm, 1 case had no significant diameter change. The mean
      follow-up time of open group was (28 +/- 23) months, mean operation time was (4.9
      +/- 0.7) hours, Mean operative blood loss was (3 300 +/- 370) ml, 1 case with
      postoperative anastomotic pseudoaneurysm formation. The EVAR group followed up
      for (20 +/- 14) months, without serious perioperative complications, 5 cases
      aneurysm diameter decreased (5.1 +/- 1.5) mm. CONCLUSION: Conservative medical
      treatment can improve clinical symptoms of IAAA, such as inflammation,
      abdominal/back pain and hydronephrosis.EVAR is gradually becoming a first-line
      treatment of IAAA.Open surgery is still the gold standard for treatment of IAAA.
      Therefore, definite conclusions should be drawn from further studies.

PMID- 24746081
TI  - [Risk factors and predictive factors of cognitive deterioration in patients of
      vascular cognitive impairment no dementia with subcortical ischemic vascular
      disease].
AB  - OBJECTIVE: To explore the independent risk factors and predictive factors of
      cognitive deterioration in patients of vascular cognitive impairment no dementia
      with subcortical ischemic vascular disease (VCIND-SIVD). METHODS: The clinical
      and neuropsychological characteristics of 96 VCIND-SIVD patients were collected
      and their cognitive states re-assessed after one year. The distribution of
      continuous and categorical variables was examined with univariate analysis. And
      Logistic regression in multivariate modeling was employed to identify the risk
      and predictive factors of cognitive deterioration. RESULTS: After 1-year follow
      up, 8 patients dropped out, 2 died and the remainder remained. There were 48
      males and 38 females with an average age of 64.3 +/- 5.4 years. Among them, 17
      (19.8%) deteriorated into dementia, 24 (27.9%) upgraded to normal cognition and
      45 (52.3%) maintained their cognitive status. They were divided into dementia
      group (cognition deteriorating into dementia) and control group
      (elevated/sustained cognition). After univariate analysis of general information
      and vascular risk factors, Logistic regression demonstrated that education level
      (P < 0.05, OR = 0.7) was a preventive factor of dementia while age (P < 0.05, OR
      = 1.2), hypertension (P < 0.05, OR = 5.6) and high homocysteine (P < 0.05, OR =
      4.2) were independent risk factors of dementia. After univariate analysis of
      neuropsychological scores, Logistic regression demonstrated that visual
      reproduction-immediate recall (P < 0.05, OR = 3.4), digit span forward (P < 0.05,
      OR = 1.2), clock drawing test (P < 0.05, OR = 6.8) and completion time of London
      tower (P < 0.05, OR = 5.4) were predictive factors of dementia. CONCLUSION: VCIND
      SIVD patients with low score of visual reproduction-immediate recall, digit span
      forward, clock drawing test and completion time of London tower should receive
      vigorous controls of hypertension and high homocysteine.

PMID- 24746082
TI  - [Neurophysiologic studies of POEMS syndrome and its related diseases].
AB  - OBJECTIVE: To explore the electrophysiological characteristics of polyneuropathy,
      organomegaly, endocrinopathy, monoclonal gammopathy and skin changes (POEMS)
      syndrome and its related diseases. METHODS: The electrophysiological
      characteristics were analyzed retrospectively from June 2000 to June 2013 in
      patients with POEMS syndrome, monoclonal gammopathy of undetermined significance
      (MGUS) and chronic inflammatory demyelinating polyradiculoneuropathy (CIDP).
      Electromyography and nerve conduction examinations of median, ulnar, tibial,
      peroneal and sural nerves were performed. RESULTS: In patients with POEMS
      syndrome, the amplitude of compound muscle action potential (CMAP) of tibial and
      peroneal nerves was lower than that of median and ulnar nerves ((1.02 +/- 0.23)
      vs (2.12 +/- 0.30) mV, (P < 0.05) ); compared with patients with CIDP, the
      amplitude of CMAP for POEMS patients was lower ((2.12 +/- 0.30) vs (3.94 +/-
      0.52) mV, (1.02 +/- 0.23) vs (3.65 +/- 0.57) mV) (P < 0.05) while terminal
      latency indices (TLI) was higher ((0.41 +/- 0.13) vs (0.22 +/- 0.01), (0.45 +/-
      0.16) vs (0.24 +/- 0.13) ) (P < 0.05) and the occurring rate of conduction block
      (CB) and temporal dispersion (TD) was lower (P < 0.05). Compared with MGUS
      patients, the amplitude of CMAP for POEMS patients was lower ((2.12 +/- 0.30) vs
      (3.81 +/- 0.83) mV, (1.02 +/- 0.23) vs (3.82 +/- 0.63) mV) (P < 0.05) ; sensory
      conduction velocity of POEMS patients was faster ((33 +/- 5) vs (20 +/- 3) m/s,
      (28 +/- 4) vs (18 +/- 3) m/s)(P < 0.05)). CONCLUSION: Nerve conduction studies of
      POEMS syndrome implicate both axonal loss and demyelination.Uniform demyelination
      is more predominant in nerve trunk rather than distal nerve terminals. CB and TD
      occur less frequently and axonal loss is length-dependent.

PMID- 24746083
TI  - [Analysis of clinical features for 8 patients with autoimmune dementia].
AB  - OBJECTIVE: To explore the clinical features and therapeutic profiles of
      autoimmune dementia. METHODS: Eight hospitalized patients with autoimmune
      dementia during March 2011 and May 2013 were recruited and retrospectively
      analyzed for clinical features, as well as therapeutic and prognosis profiles.
      RESULTS: There were 3 males and 5 females with a onset age range of 45-72 years.
      Their onsets varied from acute (n = 3), subacute (n = 1) to chronic (n = 4).Six
      of them had a fluctuating course. The diagnoses were multiple sclerosis (n = 3),
      paraneoplastic limbic encephalitis (n = 2) and Hashimoto's encephalopathy (n =
      1), microscopic polyangiitis (n = 1) and unclassified autoimmune encephalopathy
      (n = 1). Progressive memory loss without delirium was the main symptom.In
      addition, 3 patients suffered epilepsy, 2 with intractable hyponatremia, 4 with
      positive serum autoimmune or paraneoplastic antibodies, 7 with inflammatory
      cerebrospinal fluid, 4 with abnormal electroencephalography (EEG) and 8 with
      various changes on brain magnetic resonance imaging (MRI). Two patients had
      concurrent Hashimoto's thyroiditis and another with small cell lung cancer. All
      patients improved after treatment with immunological and antineoplastic
      therapies. CONCLUSION: Autoimmune dementia has complex causes with a rapidly
      progressive and fluctuating course. The coexisting conditions include epilepsy,
      hyponatremia, organ-specific autoimmunity, inflammatory spinal fluid with
      abnormal EEG and brain MRI findings.Immunotherapy is recommended.

PMID- 24746084
TI  - [Comparison analysis of multi-modalities images in 158 patients with hepatic
      tumor].
AB  - OBJECTIVE: To compare and analyze the positron emission tomography (PET) images
      with other multi-modalities in the diagnosis of hepatic tumors. METHODS: A total
      of 158 patients undergoing (18)F fluorodeoxyglucose (FDG)-PET were enrolled along
      with another 55 cases with (11)C acetate-PET (AC-PET) imaging within 1 week. The
      pathological results were taken as the golden criteria. Tumor marker, contrast
      ultrasound, computed tomography (CT) and magnetic resonance imaging (MRI) results
      were collected.SPSS 19.0 was used for statistical analysis. RESULTS: Contrast
      MRI, ultrasound and CT were more effective than PET in the differential diagnosis
      of hepatic tumor.FDG-PET showed a better accuracy in the diagnosis of
      intrahepatic cholangiocarcinomas, metastasis and rare primary hepatic carcinoma.
      AC-PET was a good complementary method to FDG-PET. Consideration of tumor size,
      amount, laboratory results and history could improve the diagnostic accuracy of
      PET and enhanced CT. CONCLUSION: PET must be combined with other image modalities
      to differentiate hepatic tumors more effectively and accurately.

PMID- 24746085
TI  - [Surveillance and diagnostic values of ultrasound, computed tomography and
      magnetic resonance imaging follow-ups in malignant transformation of cirrhotic
      nodules].
AB  - OBJECTIVE: To explore the surveillance and diagnostic values of ultrasound (US),
      computed tomography (CT) and magnetic resonance imaging (MRI) follow-ups in
      malignant transformation of cirrhotic nodules so as to improve the diagnostic
      accuracy of early hepatocellular carcinoma (HCC) with liver cirrhosis. METHODS:
      Retrospective analyses were conducted for US, CT and MRI features of 96 HCC
      patients confirmed by pathological examination or treatment. RESULTS: All
      patients (145 lesions) underwent US, CT, MRI examinations during follow-ups.US
      detected 62 lesions (42.6%) and 90 lesions on enhanced CT (62.1%) presented "fast
      in fast-out" enhancement, pseudocapsule, progressive enlargement or increasing
      numbers in a short time. And 138 nodules on MRI (95.2%) manifested as decreased
      T1WI signal, increased T2WI and DWI signal, "nodule in nodule" on T2WI, fatty
      degeneration, change of enhancement patterns, pseudocapsule, progressive
      enlargement or increased number in a short time. CONCLUSION: MRI offers obvious
      advantages over CT and US (P < 0.05). US may serve as a routine follow-up mean
      for cirrhotic patients. Once lesions are found, enhanced CT and/or MRI should be
      performed for confirming a diagnosis. Cirrhotic patients without HCC should
      undergo MRI regularly to diagnose HCC earlier.

PMID- 24746086
TI  - [Functional connectivity of temporal parietal junction in online game addicts:a
      resting-state functional magnetic resonance imaging study].
AB  - OBJECTIVE: To explore the functions of temporal parietal junction (TPJ) as parts
      of attention networks in the pathogenesis of online game addiction using resting
      state functional magnetic resonance imaging (fMRI). METHODS: A total of 17 online
      game addicts (OGA) were recruited as OGA group and 17 healthy controls during the
      same period were recruited as CON group. The neuropsychological tests were
      performed for all of them to compare the inter-group differences in the results
      of Internet Addiction Test (IAT) and attention functions. All fMRI data were
      preprocessed after resting-state fMRI scanning. Then left and right TPJ were
      selected as regions of interest (ROIs) to calculate the linear correlation
      between TPJ and entire brain to compare the inter-group differences. RESULTS:
      Obvious differences existed between OGA group (71 +/- 5 scores) and CON group (19
      +/- 7 scores) in the IAT results and attention function (P < 0.05). Compared with
      the controls, right TPJ in online game addicts showed decreased functional
      connectivity with bilateral ventromedial prefrontal cortex (VMPFC), bilateral
      hippocampal gyrus and bilateral amygdaloid nucleus, but increased functional
      connectivity with right cuneus.However, left TPJ demonstrated decreased
      functional connectivity with bilateral superior frontal gyrus and bilateral
      middle frontal gyrus, but increased functional connectivity with bilateral cuneus
      (P < 0.05). CONCLUSION: Altered functional connectivity of TPJ reflected its
      dysfunction in online game addicts.It suggests that TPJ is an important component
      of attention networks participating in the generation of online game addiction.

PMID- 24746087
TI  - [Individualized neurosurgical treatments of spastic cerebral palsy].
AB  - OBJECTIVE: To explore the outcomes of individualized neurosurgical treatments of
      spastic cerebral palsy. METHODS: A total of 452 spastic cerebral palsy patients
      undergoing microneurosurgery during March 2006 and December 2011 were
      retrospectively analyzed. Performed on the basis of clinical manifestations,
      comprehensive procedures included selective cutting of neck or lumbosacral dorsal
      root ganglia (SPR, n = 182) for multiple muscle spasm, selective peripheral
      neurotomy (SPN, n = 270) for focal muscle spasm, line tendon lengthening or
      cutting and orthopedic surgery (n = 116) for tendon contracture plus limb
      deformities and carotid artery adventitia endarterectomy (n = 46) for salivation
      plus athetoid. RESULTS: The average follow-up period was 18 (10-24) months. The
      limb spasm relief rate of SPR was 95.6% and that of SPN 98.3%. And the
      postoperative symptom improvement rate of common carotid arterial adventitia
      stripping was 91.3%. There were 8 cases (4.4%) of recurrent spasticity after SPR
      and 28 (10.4%) after SPN. CONCLUSION: Offering individualized microsurgical
      treatments on the basis of clinical manifestations is essential for patients with
      spastic cerebral palsy.

PMID- 24746088
TI  - [Relationship of mid-trimester serum screening markers and adverse pregnancy
      outcomes].
AB  - OBJECTIVE: To explore the relationship of mid-trimester serum screening markers
      and adverse pregnancy outcomes. METHODS: We retrospectively reviewed all
      obstetric patients with mid-trimester screening data who delivered at our
      department from September 2010 to November 2012. Adjusted effects were estimated
      with Logistic regression analysis. RESULTS: A total of 3 618 cases were enrolled.
      The level of free beta-subunit of human chorionic gonadotropin (fbeta-hCG) [ >=
      2.2 (multiple of median) MOM] was associated with the risk of pregnancy-related
      hypertension (OR = 2.06, 95%CI 1.18-3.60, P < 0.01). And fbeta-hCG ( >= 2.2 MOM)
      and alpha-fetoprotein (AFP) ( >= 1.88 MOM) were associated with the development
      of placenta-related complications (P < 0.01, 0.05 respectively). Additionally,
      maternal weight was associated with the risk of pregnancy-related hypertension
      and placenta-related complications (both P < 0.05). CONCLUSION: The mid-trimester
      screening markers fbeta-hCG and AFP are associated the risk of adverse pregnancy
      outcomes. And their value may predict the risk of adverse pregnancy outcomes.

PMID- 24746089
TI  - [Effects of low-frequency electrical stimulation of hippocampus on the expression
      of GABAA receptor alpha1 and beta2 subunits in kainate-kindled rats].
AB  - OBJECTIVE: To explore the effects of low-frequency electrical stimulation (LFS)
      of hippocampus on the expression of GABAA receptor alpha1 and beta2 subunits in
      the kainite (KA)-kindled rats and explore its underlying rescue mechanism for
      temporal lobe epilepsy. METHODS: The SD rats were divided into 4 groups (n =
      10):control group:no operation; epilepsy group:KA was stereotactically injected
      into rat hippocampus to establish KA-kindled model; sham-LFS group:only
      implanting of electrodes into hippocampus without LFS; LFS group:KA-kindled model
      with LFS. Then hippocampal tissues were collected and their expressions of GABAA
      receptor alpha1 and beta2 subunits measured by immunohistochemistry, quantitative
      polymerase chain reaction (q-PCR) and Western blot.Nissl staining was performed
      to detect the number of damaged hippocampal neurons. RESULTS: There were
      significant decreases of GABAA receptor alpha1 and beta2 subunits in kindled
      hippocampus (P < 0.01). LFS resulted in an effective rescue, but failed to reach
      normal levels. The damaged neurons could not be reversed according to Nissl
      staining. CONCLUSION: The hippocampal application of LFS may protect against
      seizures by modulating the expressions of alpha1 and beta2 GABAA receptor
      subunits.

PMID- 24746090
TI  - [Effects of repeated ultrasound on expression of NR1, NR2B subunit of NMDA
      receptor and synaptic structure in prenatal rats].
AB  - OBJECTIVE: To explore the effects of different doses of repeated ultrasound on
      the expressions of NR1 and NR2B subunits of NMDA receptor and synaptic structure
      so as to understand the molecular mechanisms of ultrasound on learning and memory
      in prenatal rats. METHODS: The pregnant rats were randomly divided into 3 groups
      (n = 8, each) and exposed to ultrasound for 0, 4 and 20 minutes at Days 6, 12 and
      18 of gestation respectively. Their offspring were tested by Morris water maze
      (MWM) for evaluating the learning and memory abilities at an age of 2 months. The
      hippocampal pyramidal cell was observed by hematoxylin and eosin staining, the
      expressions of NR1 and NR2B by immunohistochemistry and Western blot and the
      morphologies of synapse in CA1 by electron microscopy. RESULTS: (1) In the water
      maze test, compared with the control group, the escape latency of 4 min group was
      significantly shorter (P < 0.05) while that of 20 min group significantly longer
      in the 1-4 d latency (P < 0.01). The time in platform quadrant (TQ) and the
      frequency of crossing through original platform increased in 4 min group (P <
      0.01).However, they decreased in the 20 min group (P < 0.01); (2) in 4 min group,
      the density of hippocampal CA1 pyramidal cells per unit area was higher than that
      of the control group (P < 0.05).Sparse pyramidal cells and low density were
      observed in the 20 min group (P < 0.01); (3) compared with the control group, the
      expressions of total NR1, NR2B proteins in hippocampal regions significantly
      increased in 4 min group and both significantly decreased in 20 min (P < 0.05);
      (4) the structure of synapses became damaged in 20min group with decreased number
      density and surface density. CONCLUSION: High doses of repeated ultrasound may
      decrease the ability of learning and memory through a down-regulated expression
      of NR1 and NR2B subunits in hippocampal regions and damaging synaptic
      structure.However, low doses of repeated ultrasound may promote the expressions
      of NR1 and NR2B, maintain synaptic structure and further enhance cognitive
      ability in prenatal rats.

PMID- 24746091
TI  - [Clinical application of serum Golgi protein 73 in the diagnosis and progress of
      hepatocellular carcinoma].
AB  - OBJECTIVE: To explore the clinical application of serum GP73 in the diagnosis and
      progress of hepatocellular carcinoma (HCC). METHODS: Enzyme-linked immunosorbent
      assay was employed to quantitatively detect serum GP73 in 59 HCC patients, 23
      cases of hepatitis B virus (HBV)-related cirrhosis and 33 normal controls. The
      relationship between GP73 and diagnosis as well as progress of HCC was examined.
      RESULTS: Significant differences existed when serum GP73 was categorized by Child
      Pugh class A and B (P < 0.01). There was no correlation between GP73 levels and
      other parameters including age, gender, BCLC staging, HBV infection, tumor size,
      extrahepatic metastasis and tumor numbers. The serum GP73 with a mean level of
      [127 (147) ug/L, M(QR)] in HCC patients was significantly higher than that in
      normal controls or those with HBV-liver cirrhosis (P < 0.01). Based on the ROC
      curve analysis, the cut-off value was 99 ug/L with 64.4% sensitivity and 96.4%
      specificity. The sensitivity of diagnosing HCC with GP73 plus AFP improved (P =
      0.025) , but not in specificity.Serum GP73 and AFP did not change greatly in
      terms of response assessment in mRECIST from baseline to progressive disease (P =
      0.959, P = 0.788).No correlation existed between baseline concentration of GP73
      with AFP and time to progression (r = 0.119, P = 0.608; r = 0.142, P = 0.540) .
      CONCLUSION: GP73 may become a potential serum marker for diagnosing HCC. And a
      combination of AFP yields better outcomes. The exact relationship between mRECIST
      and GP73 as well as AFP shall be proved by large-scale clinical trials.

PMID- 24746092
TI  - Phytocystatins and their potential to control plant diseases caused by fungi.
AB  - Plant cystatins, also called phytocystatins, constitute a family of specific
      cysteine protease inhibitors found in several monocots and dicots, where they can
      be involved in the regulation of several endogenous processes and in defense
      against pests and pathogens, as well as in response to abiotic stress. In this
      mini-review we aimed to present isolated and characterized phytocystatins with
      potential use in control of plant disease caused by fungi. 

PMID- 24746093
TI  - A surfactin lipopeptide adjuvanted hepatitis B vaccines elicit enhanced humoral
      and cellular immune responses in mice.
AB  - WH1fungin (WF), a lipopeptide surfactin, has been verified as an immunoadjuvant
      previously. In this study, mice were intranasally or parenterally immunized with
      WF plus Hepatitis B surface antigen (HBsAg), then the immune responses were
      detected. The results showed 50 ug WF plus 20 MUg HBsAg for intranasal and 10 MUg
      WF plus 1 ug HBsAg for parenteral immunization was efficient inducing strong
      immune response against HBsAg in mice. A high titer and longterm anti-HBsAg IgG
      was observed for more than 19 weeks in intranasal or parenteral immunizations,
      much higher than that induced by CpG or Alum adjuvant. The anti-HBsAg IgA was
      also induced in intestine and lung, indicating that mucosal as well as systemic
      immune response was elicited for intranasal immunization. The IgG isotype in
      serum revealed WF induced a Th2-bias immune response with a higher titer of anti
      HBsAg IgG1 than IgG2a in mice. Moreover, WF also induced more Th1 cells producing
      interferon (IFN)-gamma and stronger cytotoxic T lymphocytes response than
      controls for intramuscular administration. These data further confirmed that WF
      induced Th1- as well as Th2- type immune response toward HBsAg. Taken together,
      WF-adjuvanted HBsAg elicits more effective immune response than that adjuvanted
      by Alum or CpG, suggesting its potential for development of more efficient HBV
      vaccines in the future. 

PMID- 24746094
TI  - Monitoring in the Western Pacific region shows evidence of seagrass decline in
      line with global trends.
AB  - Seagrass systems of the Western Pacific region are biodiverse habitats, providing
      vital services to ecosystems and humans over a vast geographic range. SeagrassNet
      is a worldwide monitoring program that collects data on seagrass habitats,
      including the ten locations across the Western Pacific reported here where change
      at various scales was rapidly detected. Three sites remote from human influence
      were stable. Seagrasses declined largely due to increased nutrient loading (4
      sites) and increased sedimentation (3 sites), the two most common stressors of
      seagrass worldwide. Two sites experienced near-total loss from of excess
      sedimentation, followed by partial recovery once sedimentation was reduced.
      Species shifts were observed at every site with recovering sites colonized by
      pioneer species. Regulation of watersheds is essential if marine protected areas
      are to preserve seagrass meadows. Seagrasses in the Western Pacific experience
      stress due to human impacts despite the vastness of the ocean area and low
      development pressures. 

PMID- 24746095
TI  - Mechanistic studies of highly enantio- and diastereoselective aza-Petasis-Ferrier
      rearrangement catalyzed by chiral phosphoric acid.
AB  - The precise mechanism of the highly anti- and enantioselective aza-Petasis
      Ferrier (APF) rearrangement of hemiaminal vinyl ethers catalyzed by a chiral
      phosphoric acid was investigated by undertaking experimental and theoretical
      studies. The APF rearrangement is characterized by the following unique
      mechanistic features: (i) efficient optical kinetic resolution of the starting
      racemic hemiaminal vinyl ether, (ii) enantioconvergent process from racemic
      hemiaminal vinyl ethers to optically active beta-amino aldehyde products, and
      (iii) anomalous temperature effects on the enantioselectivity (enantioselectivity
      increases as reaction temperature increases). The following experiments were
      conducted to elucidate the unique mechanistic features as well as to uncover the
      overall scheme of the present rearrangement: (A) X-ray crystallographic analysis
      of the recovered hemiaminal vinyl ether to determine its absolute configuration,
      (B) rearrangements of enantiomerically pure hemiaminal vinyl ethers to validate
      the stereochemical relationship between the hemiaminal vinyl ethers and beta
      amino aldehydes, (C) theoretical studies on the transition states of the C-O bond
      cleavage and C-C bond formation steps to gain an insight into the optical kinetic
      resolution of the hemiaminal vinyl ether and the origin of the stereoselectivity,
      as well as to elucidate the overall scheme of the present rearrangement, and (D)
      crossover experiments of two hemiaminal vinyl ethers having different vinyl ether
      and aliphatic substituents to comprehend the mechanism of the anomalous
      temperature effect and the enantioconvergent process. The results of experiments
      and theoretical studies fully support the proposed mechanism of the present anti-
      and enantioselective APF rearrangement. 

PMID- 24746097
TI  - A study relating the composition of follicular fluid and blood plasma from
      individual Holstein dairy cows to the in vitro developmental competence of pooled
      abattoir-derived oocytes.
AB  - The fertility of high-performance (high milk yield) dairy breeds such as the
      Holstein within the Australian dairy herd has been on the decline for the past
      two decades. The 12-month calving interval for pasture-based farming practices
      results in oocyte maturation coinciding with peak lactation, periods of negative
      energy balance, and energy partitioning for lactation, causing energy deficiency
      in some organ systems, including the reproductive system. Oocyte developmental
      competence (the ability to undergo successful fertilization, embryo development,
      and establishment of pregnancy) is intrinsically linked with the composition of
      follicular fluid (FF). The aim of this study was to determine if there was a
      relationship between the fat and carbohydrate levels in plasma and FF and the
      ability to support in vitro oocyte maturation (IVM). Plasma and FF were collected
      in vivo from eight Holstein cows between 52 and 151 days post-partum. Plasma
      glucose trended (P = 0.072) higher and triglyceride levels were significantly
      higher than in FF (P < 0.05), but there were no relationships between FF and
      plasma composition. Glucose FF concentration was negatively related to follicular
      lactate and nonesterified fatty acid (NEFA) levels and days post-partum.
      Conversely, FF triglyceride concentrations were positively related to FF NEFA
      levels and negatively related to milk fat and protein composition. Abattoir
      derived cumulus-oocyte complexes were cultured in either 50% FF (FF-IVM) or 50%
      plasma (plasma-IVM), with on-time embryo development then assessed. Although
      there were no differences between animals, the blastocyst rates after FF-IVM were
      negatively related to plasma glucose and days post-partum and positively related
      to body condition score and plasma NEFA levels. In comparison to the previous
      studies, total NEFA levels in FF were not related to animal parameters and did
      not influence oocyte developmental competence in vitro. Results from this study
      suggest that days post-partum and body condition score influence carbohydrate
      metabolism within the follicular environment, and this may be attributed to the
      pasture-based feed system applied in the Australian dairy industry. 

PMID- 24746098
TI  - Diagnosis of acute puerperal metritis by electronic nose device analysis of
      vaginal discharge in dairy cows.
AB  - The objective of this study was to estimate the diagnostic accuracy of an
      electronic nose device using vaginal discharge samples to diagnose acute
      puerperal metritis (APM) in dairy cows. Uterine fluid was sampled manually with a
      gloved hand and under sterile conditions for electronic nose device analysis (day
      in milk (DIM) 2, 5, and 10) and bacteriologic examination (DIM 5), respectively,
      and on additional days, if APM was diagnosed during the daily clinical
      examinations. A dataset containing samples from 70 cows was used to create a
      model and to validate the APM status predicted by this model, respectively. Half
      of the dataset (n = 35; 14 healthy and 21 metritic cows) was provided with
      information regarding the APM diagnosis and contained all three measurements (DIM
      2, 5, and 10) for each cow and was used as a training set whereas the second half
      was blinded (n = 35; 14 healthy and 21 metritic cows) and contained only the
      samples collected on DIM 5 of each cow and was used to validate the created
      prediction model. A receiver operating characteristic curve was calculated using
      the prediction results of the validation test. The best observed sensitivity was
      100% with specificity of 91.6% when using a threshold value of 0.3. The
      calculated P-value for the receiver operating characteristic curve was less than
      0.01. Overall, Escherichia coli was isolated in eight of 28 (28.6%) and 22 of 42
      (52.4%) samples collected from healthy and metritic cows, respectively.
      Trueperella pyogenes and Fusobacterium necrophorum were isolated in 14 and six of
      28 (50.0% and 21.4%) and 17 and 16 of 42 (40.5% and 38.1%) samples collected from
      healthy and metritic cows, respectively. The prevalence of Escherichia coli and
      Trueperella pyogenes was similar in the samples obtained from metritic cows used
      for the training set and the validation test. The results are promising
      especially because of the objective nature of the measurements obtained by the
      electronic nose device. 

PMID- 24746099
TI  - Synthesis of a novel UDP-carbasugar as UDP-galactopyranose mutase inhibitor.
AB  - The multistep synthesis of a novel UDP-C-cyclohexene, designed as a high energy
      intermediate analogue of the UDP-galactopyranose mutase (UGM) catalyzed
      isomerization reaction, is reported. The synthesis of the central carbasugar
      involved the preparation of a galactitol derivative bearing two olefins necessary
      for the construction of the cyclohexene ring by a ring-closing metathesis as a
      key step. Further successive phosphonylation, deprotection, and UMP coupling
      provided the target molecule. The final molecule was assayed against UGM and
      compared with UDP-C-Galf, the C-glycosidic UGM substrate analogue. 

PMID- 24746100
TI  - Iodine capture by Hofmann-Type clathrate Ni(II)(pz)[Ni(II)(CN)4].
AB  - The thermally stable Hofmann-type clathrate framework Ni(II)(pz)[Ni(II)(CN)4] (pz
      = pyrazine) was investigated for the efficient and reversible sorption of iodine
      (I2) in the gaseous phase and in solution with a maximum adsorption capacity of 1
      mol of I2 per 1 mol of Ni(II)(pz)[Ni(II)(CN)4] in solution. 

PMID- 24746101
TI  - Relationship between Hb and HbA1c in Japanese adults: an analysis of the 2009
      Japan Society of Ningen Dock database.
AB  - We investigated the effect of Hb on HbA1c levels in 265,427 Japanese individuals.
      The divergence between fasting plasma glucose (FPG) and HbA1c levels increased
      with lower Hb, resulting in HbA1c levels that were higher in relation to than the
      FPG levels. Similarly, the correlation between FPG and HbA1c levels, stratified
      by Hb, weakened as Hb decreased. 

PMID- 24746102
TI  - A new method for real-time co-registration of 3D coronary angiography and
      intravascular ultrasound or optical coherence tomography.
AB  - We present a new clinically practical method for online co-registration of 3D
      quantitative coronary angiography (QCA) and intravascular ultrasound (IVUS) or
      optical coherence tomography (OCT). The workflow is based on two modified
      commercially available software packages. Reconstruction steps are explained and
      compared to previously available methods. The feasibility for different clinical
      scenarios is illustrated. The co-registration appears accurate, robust and
      induced a minimal delay on the normal cath lab activities. This new method is
      based on the 3D angiographic reconstruction of the catheter path and does not
      require operator's identification of landmarks to establish the image
      synchronization.

PMID- 24746103
TI  - Comparison of the properties of cellulose nanocrystals and cellulose nanofibrils
      isolated from bacteria, tunicate, and wood processed using acid, enzymatic,
      mechanical, and oxidative methods.
AB  - This work describes the measurement and comparison of several important
      properties of native cellulose nanocrystals (CNCs) and cellulose nanofibrils
      (CNFs), such as crystallinity, morphology, aspect ratio, and surface chemistry.
      Measurement of the fundamental properties of seven different CNCs/CNFs, from raw
      material sources (bacterial, tunicate, and wood) using typical hydrolysis
      conditions (acid, enzymatic, mechanical, and 2,2,6,6-tetramethylpiperidinyl-1
      oxyl (TEMPO)-mediated oxidation), was accomplished using a variety of measurement
      methods. Atomic force microscopy (AFM), transmission electron microscopy (TEM),
      and 13C cross-polarization magic angle spinning (CPMAS) nuclear magnetic
      resonance (NMR) spectroscopy were used to conclude that CNCs, which are rodlike
      in appearance, have a higher crystallinity than CNFs, which are fibrillar in
      appearance. CNC aspect ratio distributions were measured and ranged from 148+/
      147 for tunicate-CNCs to 23+/-12 for wood-CNCs. Hydrophobic interactions,
      measured using inverse gas chromatography (IGC), were found to be an important
      contribution to the total surface energy of both types of cellulose. In all
      cases, a trace amount of naturally occurring fluorescent compounds was observed
      after hydrolysis. Confocal and Raman microscopy were used to confirm that the
      fluorescent species were unique for each cellulose source, and demonstrated that
      such methods can be useful for monitoring purity during CNC/CNF processing. This
      study reveals the broad, tunable, multidimensional material space in which CNCs
      and CNFs exist.

PMID- 24746104
TI  - Solid pancreatic pseudopapillary tumor managed laparoscopically in adolescents: a
      case series and review of the literature.
AB  - BACKGROUND: Solid pancreatic pseudopapillary tumors make up 1%-3% of all
      pancreatic tumors, occur predominantly in females, and usually present in the
      third and fourth decades of life. Less frequently, these tumors may present in
      children. Complete surgical excision is the treatment of choice with excellent
      outcomes. Usage of a laparoscopic approach has become more common for adult
      patients. However, the laparoscopic approach is not routinely used in the
      pediatric population. MATERIALS AND METHODS: A literature review was performed
      noting 13 documented cases of solid pancreatic pseudopapillary tumors resected
      laparoscopically in children. We report our case series of three children with a
      solid pancreatic pseudopapillary tumor treated through a minimally invasive
      approach. RESULTS: In the literature, most patients had the tumor in the body or
      distal pancreas. The most common complication was pancreatic fistula, which was
      managed with total parenteral nutrition. In addition, there were reports of
      recurrence after biopsy of the tumor. In our case series 2 of the 3 patients
      received a splenectomy because of the proximity of the tumor to the spleen. There
      were no intraoperative or postoperative complications. Follow-up length from 13
      to 36 months revealed no evidence of recurrence. CONCLUSIONS: In the pediatric
      population, solid pancreatic pseudopapillary tumors located in the body or tail
      of the pancreas can be managed with a laparoscopic distal pancreatectomy.

PMID- 24746106
TI  - Design considerations and quantitative assessment for the development of
      percutaneous mitral valve stent.
AB  - Percutaneous heart valve replacement is gaining popularity, as more positive
      reports of satisfactory early clinical experiences are published. However this
      technique is mostly used for the replacement of pulmonary and aortic valves and
      less often for the repair and replacement of atrioventricular valves mainly due
      to their anatomical complexity. While the challenges posed by the complexity of
      the mitral annulus anatomy cannot be mitigated, it is possible to design mitral
      stents that could offer good anchorage and support to the valve prosthesis. This
      paper describes four new Nitinol based mitral valve designs with specific
      features intended to address migration and paravalvular leaks associated with
      mitral valve designs. The paper also describes maximum possible crimpability
      assessment of these mitral stent designs using a crimpability index formulation
      based on the various stent design parameters. The actual crimpability of the
      designs was further evaluated using finite element analysis (FEA). Furthermore,
      fatigue modeling and analysis was also done on these designs. One of the models
      was then coated with polytetrafluoroethylene (PTFE) with leaflets sutured and put
      to: (i) leaflet functional tests to check for proper coaptation of the leaflet
      and regurgitation leakages on a phantom model and (ii) anchorage test where the
      stented valve was deployed in an explanted pig heart. Simulations results showed
      that all the stents designs could be crimped to 18F without mechanical failure.
      Leaflet functional test results showed that the valve leaflets in the fabricated
      stented valve coapted properly and the regurgitation leakage being within
      acceptable limits. Deployment of the stented valve in the explanted heart showed
      that it anchors well in the mitral annulus. Based on these promising results of
      the one design tested, the other stent models proposed here were also considered
      to be promising for percutaneous replacement of mitral valves for the treatment
      of mitral regurgitation, by virtue of their key features as well as effective
      crimping. These models will be fabricated and put to all the aforementioned tests
      before being taken for animal trials. 

PMID- 24746107
TI  - Dobrava virus carried by the yellow-necked field mouse Apodemus flavicollis,
      causing hemorrhagic fever with renal syndrome in Romania.
AB  - Hemorrhagic fever with renal syndrome (HFRS) has been confirmed by serological
      methods during recent years in Romania. In the present study, focus-reduction
      neutralization tests (FRNT) confirmed Dobrava hantavirus (DOBV) as the causative
      agent in some HFRS cases, but could not distinguish between DOBV and Saaremaa
      virus (SAAV) infections in other cases. DOBV was detected by a DOBV-specific
      TaqMan assay in sera of nine patients out of 22 tested. Partial sequences of the
      M genomic segment of DOBV were obtained from sera of three patients and revealed
      the circulation of two DOBV lineages in Romania. Investigation of rodents trapped
      in Romania found three DOBV-positive Apodemus flavicollis out of 83 rodents
      tested. Two different DOBV lineages were also detected in A. flavicollis as
      determined from partial sequences of the M and S genomic segments. Sequences of
      DOBV in A. flavicollis were either identical or closely related to the sequences
      obtained from the HFRS patients. The DOBV strains circulating in Romania
      clustered in two monophyletic groups, together with strains from Slovenia and the
      north of Greece. This is the first evidence for the circulation of DOBV in wild
      rodents and for a DOBV etiology of HFRS in Romania.

PMID- 24746108
TI  - Renal outcome after vancomycin treatment and renal replacement therapy in
      patients with severe sepsis and septic shock: a retrospective study.
AB  - PURPOSE: Acute kidney injury during systemic infections is common; however, renal
      outcome is poorly investigated. The increase of multiresistant pathogens leads to
      the use of potential nephrotoxic antibiotics as vancomycin. We investigated the
      impact of vancomycin and renal replacement therapy (RRT) for renal recovery
      during sepsis. MATERIALS AND METHODS: This is a retrospective data analysis of
      1159 patients with severe sepsis or septic shock. Logistic regression models were
      performed. RESULTS: In total, 390 (33.6%) patients required RRT during intensive
      care unit (ICU) stay; 233 (20.1%), at discharge. Admission estimated glomerular
      filtration rate (eGFR) predicted the need of RRT during stay (odds ratio [OR]
      0.969 [0.959-0.979] per increase of 1 mL/min, P<.001) and the prolonged need of
      RRT at ICU discharge (OR 0.979 [0.967-0.990], P<.001). Survivors without any RRT
      showed an improvement of eGFR at discharge, whereas patients after RRT did not
      (7.1 vs 0.8 mL/[min 1.73 m2], P<.001). The use (OR 1.648 [1.067-2.546], P<.05)
      and duration of vancomycin treatment (OR 1.043 [1.004-1.084] per each additional
      treatment day, P<.05) were predictors for ongoing RRT at discharge. CONCLUSIONS:
      Estimated GFR at ICU admission predicts renal outcome, whereas the use of
      vancomycin increases the probability of a prolonged need for RRT at discharge
      from ICU. The use of alternative antibiotics for certain patients, indicated by
      eGFR at admission, might be considered.

PMID- 24746109
TI  - Correlation of left ventricular systolic dysfunction determined by low ejection
      fraction and 30-day mortality in patients with severe sepsis and septic shock: a
      systematic review and meta-analysis.
AB  - INTRODUCTION: The prognostic implications of myocardial dysfunction in patients
      with sepsis and its association with mortality are controversial. Several tools
      have been proposed to evaluate cardiac function in these patients, but their
      usefulness beyond guiding therapy is unclear. We review the value of
      echocardiographic estimate of left ventricular ejection fraction (LVEF) in the
      setting of severe sepsis and/or septic shock and its correlation with 30-day
      mortality. METHODS: We conducted a systematic review and meta-analysis to
      evaluate the prognostic functionality of newly diagnosed LV systolic dysfunction
      by transthoracic echocardiography on critical ill patients admitted to the
      intensive care unit with severe sepsis or septic shock. RESULTS: A search of
      EMBASE and PubMed, Ovide MEDLINE, and Cochrane CENTRAL medical databases yielded
      7 studies meeting inclusion criteria reporting on a total of 585 patients. The
      pooled sensitivity of depressed LVEF for mortality was 52% (95% confidence
      interval [CI], 29%-73%), and pooled specificity was 63% (95% CI, 53%-71%).
      Summary receiver operating characteristic curve showed an area under the curve of
      0.62 (95% CI, 0.58-0.67). The overall mortality diagnostic odd ratio for septic
      patients with LV systolic dysfunction was 1.92 (95% CI, 1.27-2.899). Statistical
      heterogeneity of studies was moderate. CONCLUSION: The presence of new LV
      systolic dysfunction associated with sepsis and defined as low LVEF is neither a
      sensitive nor a specific predictor of mortality. These findings are limited
      because of the heterogeneity and underpower of the studies. Further research into
      this method is warranted.

PMID- 24746110
TI  - Longitudinal study of diffusion tensor imaging properties of affected cortical
      spinal tracts in acute and chronic hemorrhagic stroke.
AB  - This study investigated the clinical value of diffusion tensor imaging (DTI) in
      predicting the motor outcome in patients with basal ganglia hemorrhage. This
      prospective study included 23 patients assessed with DTI to measure the
      fractional anisotropy (FA) value in affected cortical spinal tract (CST) at three
      time points: day 0, day 30 and day 90 after onset. The motor function score (MFS)
      was applied to evaluate motor function and patients were divided into good and
      poor outcome groups according to the MFS on day 90. The mean FA value on day 0
      was significantly lower in the poor outcome group than in the good outcome group
      (p<0.01). FA value gradually decreased in the poor outcome group until day 90
      after onset, while it continuously increased in the good outcome group. The MFS
      obtained at day 90 after onset was significantly correlated with the initial FA
      value in the affected cerebral peduncle (r=-0.926, p<0.01). Receiver operating
      characteristic curve analysis showed that the FA value on day 0 could predict
      motor function outcome with a sensitivity of 88.89% and specificity of 92.86% at
      the initial FA value of 0.45. The FA value of affected CST in acute cerebral
      hemorrhage may valuably predict the motor function outcome and its dynamic change
      may represent the Wallerian degeneration in motor tracts after hemorrhagic
      stroke. 

PMID- 24746111
TI  - Anterior panhypopituitarism in diffuse large B-cell stage IV lymphoma.
AB  - The most common presentation of metastases to the pituitary gland in systemic
      lymphoma is diabetes insipidus resulting from infiltration of the
      infundibulum/posterior lobe. We describe a 69-year-old man with diffuse large B
      cell stage IV lymphoma who presented with anterior pituitary hypofunction,
      without features of posterior pituitary involvement. He presented with a few
      months of postural dizziness and hypotension, weight loss, fever, strabismus of
      right eye and a superficial abdominal wall mass. At this time he had no history
      of malignancy. Biochemically he had hypovolemic hyponatremia, secondary
      hypothyroidism and adrenal insufficiency. Further hormonal work-up revealed
      panhypopituitarism but no diabetes insipidus. Imaging of the brain, thorax and
      abdomen demonstrated diffuse intracranial pachymeningeal thickening and
      enhancement, multiple lymphadenopathies, a bulky right adrenal gland and a large
      left suprarenal mass, which were indicative of an infiltrative disease. Imaging
      of the pituitary showed heterogeneous enhancement of the anterior lobe with an
      unremarkable pituitary stalk and posterior lobe. Biopsy of the superficial
      abdominal wall mass revealed diffuse large B-cell lymphoma confirmed by bone
      marrow aspiration biopsy. Positron emission tomography (PET) scan confirmed
      diffuse systemic disease involving the right orbital apex, bilateral adrenal
      glands, bone and bone marrow, retroperitoneum and subcutaneous tissues; however,
      the pituitary gland, infundibulum and hypothalamus did not show any lesions on
      the PET scan. The patient was commenced on two cycles of chemotherapy but
      unfortunately died, thus recovery of pituitary function was not tested. Pure
      anterior pituitary hypofunction can uncommonly present in individuals with
      metastases to the pituitary gland, in contrast to the more common posterior
      pituitary/infundibulum involvement. 

PMID- 24746112
TI  - Development of the human fetal testis.
AB  - Masculinisation and adult fertility in the male are dependent on appropriate
      fetal endocrine programming. There is also now increasing evidence to indicate
      that the same mechanisms which regulate masculinisation also affect the general
      wellbeing of males throughout their life and, particularly, during ageing.
      Testosterone, secreted by the fetal testes, is the main factor regulating these
      processes and an understanding of fetal testis development in the human male is
      essential if we are to prevent adult reproductive disorders. This review focuses
      on what is known about human testis development and describes the effects of
      maternal smoking, a surrogate of possible xenotoxicant exposure on fetal testis
      and fetal liver function. 

PMID- 24746114
TI  - Chemical pleurodesis for prolonged postoperative air leak in primary spontaneous
      pneumothorax.
AB  - BACKGROUND/PURPOSE: Prolonged air leak is the most common complication after
      thoracoscopic operation for primary spontaneous pneumothorax (PSP), and the role
      of chemical pleurodesis in treating air leaks remains unclear. This study
      evaluated the safety and efficacy of chemical pleurodesis with a comparison
      between minocycline and OK-432. METHODS: Between 1994 and 2011, 1083 PSP patients
      were treated by thoracoscopic operation. After the operation, patients with
      persistent air leak for 3 days or more were managed by minocycline or OK-432
      pleurodesis. The demographic and outcome data for these patients were collected
      by retrospective chart review. RESULTS: Seventy-nine patients (7.3%) with
      prolonged air leak after thoracoscopy underwent minocycline pleurodesis (60
      patients) or OK-432 pleurodesis (19 patients) as the primary treatment. The
      primary success rate was 63% (38/60) for minocycline pleurodesis and 95% (18/19)
      for OK-432 pleurodesis (p = 0.009). Postpleurodesis pain was common and
      comparable between the two groups. No major complications were noted after a
      total of 121 treatments. Patients undergoing primary OK-432 pleurodesis had
      shorter durations of postpleurodesis chest drainage (mean 8.5 vs. 2.3 days; p <
      0.001) and postoperative hospital stay (mean 11.9 vs. 6.8 days; p < 0.001) than
      those undergoing primary minocycline pleurodesis. After a median follow-up of 16
      months, recurrence was noted in one patient in the OK-432 group and none in the
      minocycline group. Long-term pulmonary function in the two groups was comparable.
      CONCLUSION: Chemical pleurodesis using OK-432 or minocycline is safe and
      convenient for prolonged air leak after thoracoscopic treatment for PSP. Our
      experience suggested that OK-432 may be more effective than minocycline in
      reducing air leak.

PMID- 24746115
TI  - Sleep complaints and memory in psychotropic drug-free euthymic patients with
      bipolar disorder.
AB  - BACKGROUND/PURPOSE: Few studies have been conducted examining the genuine sleep
      condition and memory in patients with euthymic bipolar disorder. Thus we
      evaluated sleep complaints and memory functions in psychotropic drug-free
      euthymic patients with bipolar disorder. METHODS: Twenty-two psychotropic drug
      free euthymic patients with bipolar disorder and 44 healthy controls matched by
      age and sex were recruited and assessed using the Pittsburgh Sleep Quality Index
      (PSQI) and the Wechsler Memory Scale-Revised (WMS-R). RESULTS: The quality of
      sleep and memory function of the euthymic patients with bipolar disorder were
      significantly poorer than those of the controls. Both years of education and the
      hypnotic use sub-item of the PSQI were significantly correlated with visual
      memory index of the WMS-R. CONCLUSION: Sleep complaints management is important
      in euthymic patients with bipolar disorder.

PMID- 24746116
TI  - Applying the ICF-CY framework to examine biological and environmental factors in
      early childhood development.
AB  - BACKGROUND/PURPOSE: Previous cohort studies for the general pediatric population
      had a limited focus on either environmental or biological influences, or a
      specific theoretical framework. The child's development, however, is a composite
      of physical, mental, social, environmental, and personal factors. The framework
      of the International Classification of Functioning, Disability and Health
      Children and Youth Version (ICF-CY) provides a comprehensive model for
      investigating the influential factors of child development within a
      biopsychosocial perspective. METHODS: A birth cohort study followed up 122 child
      parent dyads at birth and when the children were 4 months, 6 months, and 2.5
      years old. Structural equation modeling was conducted based on the concept and
      the definitions of ICF-CY. RESULTS: The path coefficients linking exposures and
      outcome variables were significant except for the paths from birth weight to
      general development of infants and toddlers. Home environment explained 59% of
      variance of infant developmental outcomes. CONCLUSION: The proposed model based
      on ICF-CY showed acceptable fit to the data and provides support for the
      importance of the home environment on general development of infants and
      toddlers.

PMID- 24746113
TI  - Molecular mechanism and therapeutic modulation of high mobility group box 1
      release and action: an updated review.
AB  - High mobility group box 1 (HMGB1) is an evolutionarily conserved protein, and is
      constitutively expressed in virtually all types of cells. Infection and injury
      converge on common inflammatory responses that are mediated by HMGB1 secreted
      from immunologically activated immune cells or passively released from
      pathologically damaged cells. Herein we review the emerging molecular mechanisms
      underlying the regulation of pathogen-associated molecular patterns (PAMPs)
      induced HMGB1 secretion, and summarize many HMGB1-targeting therapeutic
      strategies for the treatment of infection- and injury-elicited inflammatory
      diseases. It may well be possible to develop strategies that specifically
      attenuate damage-associated molecular patterns (DAMPs)-mediated inflammatory
      responses without compromising the PAMPs-mediated innate immunity for the
      clinical management of infection- and injury-elicited inflammatory diseases.

PMID- 24746117
TI  - Reliability and validity of the Taiwan Chinese version of the Lower Extremity
      Functional Scale.
AB  - BACKGROUND/PURPOSE: The Lower Extremity Functional Scale (LEFS) is a region
      specific functional outcome measure designed for patients with lower extremity
      musculoskeletal dysfunction. In this study, a Taiwan Chinese version was adapted
      and its validity and reliability were tested. METHODS: The LEFS questionnaire was
      adapted and tested in 159 patients with lower extremity disorders from two
      university hospitals. The Cronbach alpha-coefficient value was calculated for
      internal consistency. Intraclass correlation coefficient (ICC), Bland-Altman
      plot, and minimal detectable change (MDC) were used for evaluating the test
      retest reliability and agreement in 40 patients followed up within 7 days.
      Construct and convergent/divergent validity were examined by principal component
      analysis and correlation was examined with the Medical Outcomes Study Short Form
      36 (SF-36) questionnaire. RESULTS: The internal consistency and test-retest
      reliability of the adapted LEFS questionnaire were satisfactory [Cronbach alpha:
      0.98; ICC(2,1), 0.97]. The Bland-Altman plot of the two tests showed a relatively
      consistent distribution, with limits of agreement in the range of -9.32 to 13.02.
      The MDC at 90% confidence interval was 9.6. One-factor model was confirmed by
      principal component analysis. Also, there was a moderate association between the
      LEFS and the physical component scores and several subscales of SF-36, but not
      with the mental component scores. CONCLUSION: The Taiwan Chinese version of the
      LEFS questionnaire is a valid and reliable measure of health status for patients
      with lower extremity disorders.

PMID- 24746118
TI  - Reversing rapidly deteriorating lung function in eosinophilic bronchiolitis by
      pulse steroid and anti-IgE therapy.

PMID- 24746119
TI  - Polyethyleneimine as a promoter layer for the immobilization of cellobiose
      dehydrogenase from Myriococcum thermophilum on graphite electrodes.
AB  - Cellobiose dehydrogenase (CDH) is a promising enzyme for the construction of
      biofuel cell anodes and biosensors capable of oxidizing aldoses as cellobiose as
      well as lactose and glucose and with the ability to connect to an electrode
      through a direct electron transfer mechanism. In the present study, we point out
      the beneficial effect of a premodification of spectrographic graphite electrodes
      with the polycation polyethyleneimine (PEI) prior to adsorption of CDH from
      Myriococcum thermophilum (MtCDH). The application of PEI shifts the pH optimum of
      the response of the MtCDH modified electrode from pH 5.5 to 8. The catalytic
      currents to lactose were increased up to 140 times, and the K(M)(app) values were
      increased up to 9 times. The previously investigated, beneficial effect of
      divalent cations on the activity of CDH was also present for graphite/PEI/MtCDH
      electrodes but was less pronounced. Polarization curves revealed a second
      unexpected catalytic wave for graphite/PEI/MtCDH electrodes especially pronounced
      at pH 8. Square wave voltammetric studies revealed the presence of an unknown
      redox functionality present at 192 mV vs Ag|AgCl (0.1 M KCl) at pH 8, probably
      originating from an oxidized adenosine derivative. Adenosine is a structural part
      of the flavin adenine dinucleotide (FAD) cofactor of the dehydrogenase domain of
      CDH. It is suggested that for some enzyme molecules FAD leaks out from the active
      site, adsorbs onto graphite, and is oxidized on the electrode surface into a
      product able to mediate the electron transfer between CDH and the electrode. PEI
      is suggested and discussed to act in several manners by (a) increasing the
      surface loading of the enzyme, (b) possibly increasing the electron transfer rate
      between CDH and the electrode, and (c) facilitating the creation or
      immobilization of redox active adenosine derivatives able to additionally mediate
      the electron transfer between CDH and the electrode.

PMID- 24746121
TI  - Naphthoquinone-directed C-H annulation and C(sp3)-H bond cleavage: one-pot
      synthesis of tetracyclic naphthoxazoles.
AB  - One-pot synthesis of tetracyclic naphthoxazole derivatives from electron
      deficient naphthoquinones and alkynes was achieved via Rh(III)-catalyzed C-H
      activation and C(sp(3))-H bond cleavage for the first time. This approach
      proceeds through a tandem cascade process involving substrate tautomerization, C
      H activation, oxidative addition, cyclization, and aromatization. In addition,
      broad substrate scope, simple starting materials, and steric tolerance make this
      strategy of great practicality.

PMID- 24746123
TI  - Assessment of hand kinematics using inertial and magnetic sensors.
AB  - BACKGROUND: Assessment of hand kinematics is important when evaluating hand
      functioning. Major drawbacks of current sensing glove systems are lack of
      rotational observability in particular directions, labour intensive calibration
      methods which are sensitive to wear and lack of an absolute hand orientation
      estimate. METHODS: We propose an ambulatory system using inertial sensors that
      can be placed on the hand, fingers and thumb. It allows a full 3D reconstruction
      of all finger and thumb joints as well as the absolute orientation of the hand.
      The system was experimentally evaluated for the static accuracy, dynamic range
      and repeatability. RESULTS: The RMS position norm difference of the fingertip
      compared to an optical system was 5+/-0.5 mm (mean +/- standard deviation) for
      flexion-extension and 12.4+/-3.0 mm for combined flexion-extension abduction
      adduction movements of the index finger. The difference between index and thumb
      tips during a pinching movement was 6.5+/-2.1 mm. The dynamic range of the
      sensing system and filter was adequate to reconstruct full 80 degrees movements
      of the index finger performed at 116 times per minute, which was limited by the
      range of the gyroscope. Finally, the reliability study showed a mean range
      difference over five subjects of 1.1+/-0.4 degrees for a flat hand test and 1.8+/
      0.6 degrees for a plastic mold clenching test, which is smaller than other
      reported data gloves. CONCLUSION: Compared to existing data gloves, this research
      showed that inertial and magnetic sensors are of interest for ambulatory analysis
      of the human hand and finger kinematics in terms of static accuracy, dynamic
      range and repeatability. It allows for estimation of multi-degree of freedom
      joint movements using low-cost sensors.

PMID- 24746124
TI  - Invited review: Enteric methane in dairy cattle production: quantifying the
      opportunities and impact of reducing emissions.
AB  - Many opportunities exist to reduce enteric methane (CH4) and other greenhouse gas
      (GHG) emissions per unit of product from ruminant livestock. Research over the
      past century in genetics, animal health, microbiology, nutrition, and physiology
      has led to improvements in dairy production where intensively managed farms have
      GHG emissions as low as 1 kg of CO2 equivalents (CO2e)/kg of energy-corrected
      milk (ECM), compared with >7 kg of CO2 e/kg of ECM in extensive systems. The
      objectives of this review are to evaluate options that have been demonstrated to
      mitigate enteric CH4 emissions per unit of ECM (CH4/ECM) from dairy cattle on a
      quantitative basis and in a sustained manner and to integrate approaches in
      genetics, feeding and nutrition, physiology, and health to emphasize why herd
      productivity, not individual animal productivity, is important to environmental
      sustainability. A nutrition model based on carbohydrate digestion was used to
      evaluate the effect of feeding and nutrition strategies on CH4/ECM, and a meta
      analysis was conducted to quantify the effects of lipid supplementation on
      CH4/ECM. A second model combining herd structure dynamics and production level
      was used to estimate the effect of genetic and management strategies that
      increase milk yield and reduce culling on CH4/ECM. Some of these approaches
      discussed require further research, but many could be implemented now. Past
      efforts in CH4 mitigation have largely focused on identifying and evaluating CH4
      mitigation approaches based on nutrition, feeding, and modifications of rumen
      function. Nutrition and feeding approaches may be able to reduce CH4/ECM by 2.5
      to 15%, whereas rumen modifiers have had very little success in terms of
      sustained CH4 reductions without compromising milk production. More significant
      reductions of 15 to 30% CH4/ECM can be achieved by combinations of genetic and
      management approaches, including improvements in heat abatement, disease and
      fertility management, performance-enhancing technologies, and facility design to
      increase feed efficiency and life-time productivity of individual animals and
      herds. Many of the approaches discussed are only partially additive, and all
      approaches to reducing enteric CH4 emissions should consider the economic impacts
      on farm profitability and the relationships between enteric CH4 and other GHG.

PMID- 24746125
TI  - Evaluation of udder firmness by palpation and a dynamometer.
AB  - Swelling of the mammary gland is an important health status sign for clinical
      exploration and palpation is a routine diagnostic tool for mastitis detection in
      dairy cows. Data on repeatability or validity of specific methods of udder
      palpation are rare. The overall objective was to study the validity of estimates
      of udder firmness generated by palpation and by using a validated dynamometer.
      Specifically, we set out to determine within-observer repeatability and between
      observer repeatability in 2 specific experiments. Additionally, we compared a 4
      point palpation scoring system with estimates obtained with a dynamometer in this
      study. In a pilot trial, we determined the range of udder firmness of 25 cows and
      developed an in vitro model for udder firmness. This model enabled training of
      the observers and allowed investigating a 4-point palpation scoring system. In
      vivo, udder firmness was determined before and after milking by palpation and by
      using a dynamometer. Within-observer repeatability based on estimates of udder
      firmness of 25 cows obtained by 3 observers on a single day by palpation was
      0.968. Within-observer repeatability of estimates of udder firmness of 25 cows
      obtained with the dynamometer by a single observer was 0.997. The coefficient of
      variation of the same measures was 9.1%. To determine between-observer
      repeatability (palpation: 0.932; dynamometer: 0.898), udder firmness of 100 cows
      was measured on 4 different days by 9 observers in experiment 2. Udder firmness
      in dairy cows could be measured repeatably with the dynamometer and by palpation,
      especially when performed by a single observer. Estimates of udder firmness
      generated by palpation and with the dynamometer were moderately related
      (correlation coefficient = 0.54). Training of observers through the pilot trial
      or practical experience in the 4 d of the study in experiment 2 did not improve
      the correlation. Further research is warranted to understand how udder firmness
      develops in infected udders.

PMID- 24746126
TI  - The effect of rumen digesta inoculation on the time course of recovery from
      classical diet-induced milk fat depression in dairy cows.
AB  - Ten ruminally cannulated cows were used in a crossover design that investigated
      the effect of rumen digesta inoculation from non-milk fat-depressed cows on
      recovery from classical diet-induced milk fat depression (MFD) characterized by
      reduced fat yield, reduced de novo milk fat synthesis, and increased alternate
      trans isomers. Two additional cows fed a high-fiber and low-polyunsaturated fatty
      acid (FA) diet (31.8% neutral detergent fiber, 4.2% FA, and 1.2% C18:2) were used
      as rumen digesta donors. Milk fat depression was induced during the first 10d of
      each period by feeding a low-fiber and high-polyunsaturated FA diet (induction;
      26.1% neutral detergent fiber, 5.8% FA, and 1.9% C18:2), resulting in a 30%
      decrease in milk fat yield. A recovery phase followed where all cows were
      switched to the high-forage, low-polyunsaturated FA diet and were allocated to
      (1) control (no inoculation) or (2) ruminal inoculation with donor cow digesta (8
      kg/d for 6d). Milk yield and composition were measured every 3d. Milk yield
      progressively decreased during recovery. Milk fat concentration increased
      progressively during the recovery phase and no effect of treatment existed at any
      time point. Also, no treatment effect of milk fat yield was detected. The
      concentration of milk de novo FA increased progressively during recovery for both
      treatments and was higher for inoculated compared with control cows on d 6. In
      agreement, milk fat concentration of trans-10,cis-12 conjugated linoleic acid
      decreased progressively in both treatments and was lower in inoculated cows on d
      3 and 6. Ruminal inoculation from non-milk fat-depressed cows did not change milk
      fat yield, but slightly accelerated the rate of recovery of de novo FA synthesis
      and normal ruminal FA biohydrogenation, demonstrating a possible opportunity for
      other interventions that improve the ruminal environment to accelerate recovery
      from this condition.

PMID- 24746127
TI  - Physicochemical, microbial, and sensory properties of nanopowdered eggshell
      supplemented yogurt during storage.
AB  - This study was carried out to investigate the possibility of adding nanopowdered
      eggshell (NPES) into yogurt to improve the functionality of yogurt and the
      effects of adding NPES on the physicochemical, microbial, and sensory properties
      of the products during storage. The pH and mean lactic acid bacteria counts of
      NPES-added (0.15-0.45%, wt/vol) yogurt ranged from 4.31 to 4.66 and from 6.56 *
      10(8) to 8.56 * 10(8)cfu/mL, respectively, whereas these values ranged from 4.13
      to 4.44 and 8.46 * 10(8) to 1.39 * 10(9), respectively, for the control samples
      during storage at 5  degrees C for 16d, which indicates a prolonged shelf-life
      with NPES-supplemented yogurt. Color analysis showed that the lightness (L*) and
      position between red and green (a*) values were not significantly influenced by
      the addition of NPES. However, the position between yellow and blue (b*) value
      significantly increased with the addition of the concentration (0.45%, wt/vol) of
      NPES at d 16 of storage. Sensory evaluation revealed that NPES-added yogurts
      showed a notably less sourness score and a higher astringency score than the
      control. An earthy flavor was higher in 0.45% NPES-supplemented yogurt compared
      with the control. Based on the results obtained from the current study, the
      concentration (0.15 to 0.30%, wt/vol) of NPES can be used to formulate NPES
      supplemented yogurt without any significant adverse effects on the
      physicochemical, microbial, and sensory properties.

PMID- 24746128
TI  - Short communication: Effects of molasses products on productivity and milk fatty
      acid profile of cows fed diets high in dried distillers grains with solubles.
AB  - Previous research has shown that replacing up to 5% [of dietary dry matter (DM)]
      corn with cane molasses can partially alleviate milk fat depression when cows are
      fed high-concentrate, low-fiber rations containing dried distillers grains with
      solubles. The primary objective of this study was to determine whether dietary
      molasses alters milk fatty acid (FA) profile or improves solids-corrected milk
      yield in the context of a more typical lactation diet. A secondary objective was
      to assess production responses to increasing rumen-degradable protein supply when
      molasses was fed. Twelve primiparous and 28 multiparous Holstein cows (196 +/- 39
      d in milk) were blocked by parity and assigned to 4 pens. Pens were randomly
      allocated to treatment sequence in a 4 * 4 Latin square design, balanced for
      carryover effects. Treatment periods were 21 d, with 17 d for diet adaptation and
      4 d for sample and data collection. Treatments were a control diet, providing 20%
      dried distillers grains with solubles (DM basis), 35% neutral detergent fiber,
      30% starch, and 5% ether extract; a diet with 4.4% cane molasses replacing a
      portion of the corn grain; a diet with 2.9% molasses supplement containing 32%
      crude protein on a DM basis; and a diet with 5.8% (DM basis) molasses supplement.
      Animal-level data were analyzed using mixed models, including the fixed effect of
      treatment and the random effects of period, pen, period * pen interaction, and
      cow within pen to recognize pen as the experimental unit. Diets did not alter DM
      intake, milk production, milk component concentration or yield, feed efficiency
      (DM intake/milk yield), body weight change, or milk somatic cell count. Milk
      stearic acid content was increased by the diet containing 5.8% molasses
      supplement compared with the control diet and the diet containing 2.9% molasses
      supplement, but the magnitude of the effect was small (12.27, 11.75, and 11.69 +/
      0.29 g/100g of FA). Production data revealed a dramatic effect of period on milk
      fat content and yield. Milk fat content decreased during the course of the
      experiment (least squares means = 3.16, 2.81, 2.93, and 2.64 +/- 0.09% for
      periods 1 to 4, respectively), as did milk fat yield (1.20, 1.03, 0.98, and 0.79
      +/- 0.05 kg/d). Exchanging molasses-based products for corn at 2.9 to 5.8% of
      dietary DM did not influence productivity and had minute effects on milk FA
      profile. The limited responses in this study may have been influenced by dietary
      unsaturated FA content or the advancing stage of lactation of cows in the study.

PMID- 24746129
TI  - Start-up and operating costs for artisan cheese companies.
AB  - Lack of valid economic data for artisan cheese making is a serious impediment to
      developing a realistic business plan and obtaining financing. The objective of
      this study was to determine approximate start-up and operating costs for an
      artisan cheese company. In addition, values are provided for the required size of
      processing and aging facilities associated with specific production volumes.
      Following in-depth interviews with existing artisan cheese makers, an economic
      model was developed to predict costs based on input variables such as production
      volume, production frequency, cheese types, milk types and cost, labor expenses,
      and financing. Estimated values for start-up cost for processing and aging
      facility ranged from $267,248 to $623,874 for annual production volumes of 3,402
      kg (7,500 lb) and 27,216 kg (60,000 lb), respectively. First-year production
      costs ranged from $65,245 to $620,094 for the above-mentioned production volumes.
      It is likely that high start-up and operating costs remain a significant entry
      barrier for artisan cheese entrepreneurs.

PMID- 24746130
TI  - Monitoring the bulk milk antibody response to bovine viral diarrhea in dairy
      herds vaccinated with inactivated vaccines.
AB  - This study was designed to determine long-term responses in dairy herds after
      vaccination with 1 of 3 inactivated bovine viral diarrhea virus (BVDV) vaccines
      with regard to antibodies against p80 protein in bulk tank milk samples, as
      detected by ELISA. In the present study, 29 dairy herds were vaccinated with
      Bovilis BVD (MSD Animal Health, Milton Keynes, UK), 11 with Hiprabovis Balance
      (Laboratorios Hipra, Amer, Spain), and 9 with Pregsure BVD (Zoetis, Florham Park,
      NJ). In these herds, bulk tank milk samples were collected and examined at the
      time of the first vaccination and every 6 mo during a 3-yr period. Samples were
      analyzed with a commercial ELISA test for the p80 protein of BVDV. The results
      demonstrated that vaccination affected the level of antibodies against p80.
      Hence, vaccination status should be taken into consideration when interpreting
      bulk tank milk antibody tests.

PMID- 24746131
TI  - Space allowance and barriers influence cow competition for mixed rations fed on a
      feed-pad between bouts of grazing.
AB  - The objective of this experiment was to evaluate how feeding space allowance and
      provision of feed barriers interact to affect feeding and social behavior of
      dairy cows fed a partial mixed ration on a feed-pad. The treatments were
      factorial with 3 feeding space allowances (0.6, 0.75, or 1.0m of trough space per
      cow) and feed troughs that were either open or had head barriers that physically
      separated adjacent cows to reduce interactions during feeding. One hundred and
      forty-four Holstein-Friesian cows in mid lactation were allocated into 12 groups
      of 12 cows, with 1 of 6 treatments (3 * 2) randomly assigned to 2 groups out of
      12. Treatments were changed weekly over 3 wk according to a row-column, crossover
      design, with week corresponding to rows and group corresponding to columns. Thus,
      the design included 2 replicated groups per treatment in each week. Grazed
      pasture intake was approximately 6.1 kg of dry matter (DM)/cow per day,
      supplemented with 3.5 kg of DM/cow per day of wheat (Triticum aestivum) grain fed
      during milking and 10.7 kg of DM/cow per day of a mixed ration offered on the
      feed-pad after each milking. The experiment comprised a 7-d pre-experimental
      period followed by a 21-d experimental period. The social hierarchy within each
      group was determined before the experiment commenced. Feeding and social
      behaviors of cows were analyzed using video recordings and the changes in heart
      rate and heart rate variability were determined using heart rate monitors. Data
      were analyzed using mixed effect models by REML. When feeding space allowance was
      increased, we observed an increase in the time a cow spent feeding and a decrease
      in the number of feeding bouts in relation to the total time feed was available,
      particularly in subordinate cows. The number of aggressive behaviors and
      displacements decreased when space allowance increased. In addition, HR was
      reduced and the reduction was more pronounced in subordinate cows compared with
      dominant cows. Use of feed barriers increased cow feeding time and decreased the
      number of feeding bouts in relation to the total time feed was available,
      particularly in subordinate cows, and reduced the number of cow displacements
      during feeding. We conclude that increasing the feeding space from 0.6 to 0.75 to
      1.0m reduces aggressive interactions and improves cow feeding behavior, with the
      effects being greatest for subordinate cows. The use of feed barriers further
      reduces competition at the feed trough in a partial mixed ration feeding system.

PMID- 24746133
TI  - Short communication: Intestinal digestibility of amino acids in fluid- and
      particle-associated rumen bacteria determined using a precision-fed cecectomized
      rooster bioassay.
AB  - Microbial protein represents the majority of metabolizable protein absorbed by
      ruminant animals. Enhanced understanding of the AA digestibility of rumen
      microbes will improve estimates of metabolizable protein. The objective of this
      experiment was to determine the digestibility of AA in fluid- (FAB) and particle
      associated bacteria (PAB) using the precision-fed cecectomized rooster bioassay.
      Bacteria were isolated from 4 ruminally cannulated lactating Holstein cows by
      differential centrifugation, including particle suspension in 0.1% Tween-80 for
      increased removal of PAB from ruminal digesta. Samples of FAB and PAB were fed to
      9 cecectomized roosters to determine standardized digestibility of AA. Total AA
      digestibility was 76.8 and 75.5% for FAB and PAB, respectively, but did not
      differ. Differences existed in AA digestibilities within bacterial type when
      compared with the mean essential AA digestibility value. Compared with previous
      literature estimates of AA digestibility in microbes (mean = 76%; range = 57-87%)
      and relative to National Research Council estimates of total AA from rumen
      bacteria (80%), the precision-fed cecectomized rooster assay is an acceptable in
      vivo model to determine AA digestibility of rumen bacteria. 

PMID- 24746132
TI  - Evaluation of the use of dry cow antibiotics in low somatic cell count cows.
AB  - The goal of dry cow therapy (DCT) is to reduce the prevalence of intramammary
      infections (IMI) by eliminating existing IMI at drying off and preventing new IMI
      from occurring during the dry period. Due to public health concerns, however,
      preventive use of antibiotics has become questionable. This study evaluated
      selective DCT in 1,657 cows with low somatic cell count (SCC) at the last milk
      recording before drying off in 97 Dutch dairy herds. Low SCC was defined as
      <150,000 cells/mL for primiparous and <250,000 cells/mL for multiparous cows. A
      split-udder design was used in which 2 quarters of each cow were treated with dry
      cow antibiotics and the other 2 quarters remained as untreated controls. The
      effect of DCT on clinical mastitis (CM), bacteriological status, SCC, and
      antibiotic use were determined at the quarter level using logistic regression and
      chi-squared tests. The incidence rate of CM was found to be 1.7 times (95%
      confidence interval = 1.4-2.1) higher in quarters dried off without antibiotics
      as compared with quarters dried off with antibiotics. Streptococcus uberis was
      the predominant organism causing CM in both groups. Somatic cell count at calving
      and 14 d in milk was significantly higher in quarters dried off without
      antibiotics (772,000 and 46,000 cells/mL, respectively) as compared with the
      quarters dried off with antibiotics (578,000 and 30,000 cells/mL, respectively).
      Quarters with an elevated SCC at drying off and quarters with a positive culture
      for major pathogens at drying off had a higher risk for an SCC above 200,000
      cells/mL at 14 d in milk as compared with quarters with a low SCC at drying off
      and quarters with a negative culture for major pathogens at drying off. For
      quarters that were culture-positive for major pathogens at drying off, a trend
      for a higher risk on CM was also found. Selective DCT, not using DCT in cows that
      had a low SCC at the last milk recording before drying off, significantly
      increased the incidence rate of CM and SCC. The decrease in antibiotic use by
      drying off quarters without DCT was not compensated by an increase in antibiotic
      use for treating CM. Total antibiotic use related to mastitis was reduced by 85%
      in these quarters.

PMID- 24746134
TI  - Survey of preweaning dairy calf-rearing practices in Czech dairy herds.
AB  - It is important to describe weaknesses in rearing calves not only to improve
      their welfare, but also to detect areas where current scientific knowledge is
      poorly integrated into practice. A survey of preweaning calf-rearing practices
      was conducted using a farmer questionnaire. The survey included 136 farms,
      representing 11.9% of all dairy cows in the Czech Republic. Mean herd size (+/-
      standard deviation) was 326 +/- 131.4 cows, and mean milk production 7,413 +/-
      1,389.5 kg per cow per year. We evaluated 59 farms with Holsteins (H) and 77 with
      the Czech Fleckvieh breed (C). The survey revealed that (1) calving in group pens
      predominated (67.6% of farms); (2) no disinfection of calf navels occurred on
      11.8% of herds; (3) pooled colostrum was fed on 15.4% of farms; (4) colostrum
      quality was controlled on only 44.1% of farms, and only 73.5% of farms had
      reserve colostrum stocks; (5) nonmarket waste milk was fed in 64.7% of herds but
      it was pasteurized in only in 6.8% of herds and acidified in 35.2% of herds; (6)
      milk replacer was mixed with nonmarket waste milk on 52.9% of farms; (7) 58.8% of
      farms enabled calves to obtain milk by sucking and 41.2% by drinking from a
      bucket; (8) the main criterion in weaning was calf age (61.7%), followed by
      acceptance of starter and concentrated feed (19.9%) and lack of housing capacity
      (18.4%); and (9) newborn calves were individually housed on 96.7% of farms and
      group-housed on 3.3% of farms. The most marked differences in calf-rearing
      management between Holstein and Czech Fleckvieh farms were (1) a higher
      proportion of operations calving in tie-stalls or stanchions in C (6.5%) versus H
      (1.7%) farms; (2) a higher proportion of untreated navels on C (15.6%) versus H
      (6.8%) farms; (3) a lower proportion of C (11.7%) versus H (20.4%) farms feeding
      pooled colostrum; (4) a lower proportion of C (39%) versus H (50.9%) farms
      monitoring colostrum quality; (5) sucking milk from nipple buckets predominated
      (61%) on C farms, whereas drinking from an open bucket was most common (64.4%) on
      H farms; (6) age was the main criterion in weaning calves of both breeds (C
      farms: 55.8%, H farms: 69.5%), whereas the second most important criterion was
      lack of housing capacity (28.6% of farms) on C farms and the amount of consumed
      starter (25.4%) on H farms. We observed a difference in duration of colostrum
      period between C herds (median 5d) and H herds (median 4d). A tendency was
      observed for age of calves at weaning (C herds: median at 9.1 wk, H herds: median
      at 10 wk).

PMID- 24746135
TI  - Short communication: Dipping efficiency and teat dip residues in milk using an
      automatic dipping system.
AB  - Prototypes of the automatic-dipping system Apollo were tested with the IQ milking
      cluster (GEA Farm Technologies GmbH, Bonen, Germany) to determine the teat-dip
      residues in the milk and the dipping performance (number of dipped teats) of the
      system compared with manual (hand) dipping. A laboratory trial and a field trial
      at a dairy farm were performed to determine the iodine level in the milk when an
      iodine-based teat dip was used. In the laboratory trial, the mean difference
      between the 53 paired samples (sampling upstream and downstream of the cluster)
      was 18.9 +/- 3.18 MUg of iodine/kg. A field trial at a 300-cow commercial dairy
      farm consisted of taking 2 sets of individual cow milk samples 6 wk apart. Three
      weeks before the second test day, the iodine-based teat dip was replaced by an
      iodine-free teat dip. The mean difference between the 2 sets of 55 samples was
      25.1 +/- 5.22 MUg/kg. Compared with manually applying an iodine-based teat dip,
      the increase in the iodine content resulting from the use of the tested cluster
      with automatic dipping was very low and would not be an issue of food safety. The
      dipping performance tests were completed on the same 300-cow commercial dairy
      farm as the field iodine level trial was performed. In total, 4,541 teats from
      307 cows were observed on 4 consecutive days, showing a 91.6 +/- 1.3% success
      rate.

PMID- 24746136
TI  - Immunologic and mass-spectrometric estimates of SHBG concentrations in healthy
      women.
AB  - OBJECTIVE: Sex-hormone binding globulin (SHBG) concentrations across the adult
      female lifespan are not well defined. To address this knowledge gap, SHBG was
      quantified by both immunological and criterion methods, viz, mass spectrometry
      (MS). METHODS:  SETTING: Center for Translational Science Activities (CTSA).
      PARTICIPANTS: Healthy nonpregnant women (N=120) ages 21 to 79 years. OUTCOMES:
      SHBG, testosterone (T), estradiol (E2) and estrone (E1) each determined by MS.
      Uni- and multivariate regression of SHBG concentrations on age, body mass index
      (BMI), total and visceral abdominal fat (TAF, AVF), albumin, glucose, insulin,
      sex steroids, selected cytokines, blood pressure, and lipids. RESULTS: By
      univariate regression, MS-estimated SHBG correlated negatively with BMI, TAF,
      AVF, insulin, free T and bioavailable T (bio T) (each P<=10(-4)), but not with
      blood pressure or lipids. By stepwise multivariate regression analysis, free and
      total T (both positive) and bio T (negative) were correlated with SHBG in all 4
      assays (each P<10(-15), R(2)>=0.481). In addition, TAF and BMI were negatively
      associated with SHBG (P<=0.0066) in 2 SHBG assays, and estrone and IL-8 with SHBG
      weakly (P<=0.035) in one SHBG assay each. When nonsignificant cytokines were
      excluded, SHBG was jointly associated with AVF, total T and HDL (P<10(-9),
      R(2)=0.358). CONCLUSION: According to MS, three metabolic factors, T, AVF and
      HDL, together explain more than one-third of the interindividual variation in
      SHBG levels. We speculate that these measures reflect insulin action.

PMID- 24746137
TI  - TRIB3 alters endoplasmic reticulum stress-induced beta-cell apoptosis via the NF
      kappaB pathway.
AB  - OBJECTIVE: To examine the effect of TRIB3 on endoplasmic reticulum stress induced
      beta-cell apoptosis and to investigate the mechanism with a specific emphasis on
      the role of NF-kappaB pathway. MATERIALS/METHODS: We investigated the effect of
      TRIB3 on ER stress-induced beta-cell apoptosis in INS-1 cells and primary rodent
      islets. The potential role of TRIB3 in ER stress inducer thapsigargin (Tg)
      induced beta-cell apoptosis was assessed using overexpression and siRNA knockdown
      approaches. Inducible TRIB3 beta-cells, regulated by the tet-on system, were used
      for sub-renal capsule transplantation in streptozotocin (STZ)-diabetic mice, to
      study the effect of TRIB3 on ER stress-induced beta-cell apoptosis in vivo.
      Apoptosis was determined by TUNEL staining both in vivo and in vitro, while the
      molecular mechanisms of NF-kappaB activation were investigated. RESULTS: TRIB3
      was induced in ER-stressed INS-1 cells and rodent islets, and its overexpression
      was accompanied by increased beta-cell apoptosis. Specifically, TRIB3
      overexpression enhanced Tg-induced INS-1 derived beta-cell apoptosis both in
      vitro and in sub-renal capsular transplantation animal model. Additionally,
      knockdown of Trib3 blocked Tg-induced apoptosis. Mechanistically, the induction
      of TRIB3 during ER stress resulted in the activation of NF-kappaB and aggravated
      INS-1 derived beta-cell apoptosis, while inhibiting the NF-kappaB pathway
      significantly abrogated this response and prevented beta-cell apoptosis, both in
      vitro and in sub-renal capsular transplantation animal model. CONCLUSION: TRIB3
      mediated ER stress-induced beta-cell apoptosis via the NF-kappaB pathway.

PMID- 24746138
TI  - Improving the prompt identification of the Emergency Severity Index level 2
      patient in triage: rapid triage and the registered nurse greeter.
AB  - INTRODUCTION: High triage volumes can delay rapid identification of walk in ESI
      level 2 patients. This concern coupled with persistently increasing volumes
      prompted the Reading Hospital Emergency Department to move from single-tiered
      triage to duel-tiered rapid triage in 2008, then brought the addition of the RN
      Greeter in 2011. The purpose of this study was to assess how rapid triage then
      the RN Greeter impacted the ability to quickly identify the walk-in ESI 2
      patient. METHODS: A retrospective analysis of mini-registration to triage time
      was conducted on ESI level 2 patients entering the ED by means other than
      ambulance. Data was collected from three separate time frames: The first
      representing single-tiered triage, the second duel-tiered rapid triage, and the
      third duel-tiered triage with the RN Greeter. RESULTS: Data demonstrated despite
      increasing volumes both rapid triage and the RN Greeter improved the prompt
      identification of ESI 2 patients. DISCUSSION: While moving from single to duel
      tiered triage met little resistance from staff, the RN Greeter role was initially
      not as well received. However, as empirical data demonstrated the efficacy of the
      RN Greeter to quickly identify the potential ESI 2 patient, the role ultimately
      became an integral part of triage.

PMID- 24746139
TI  - Direct growth of high-quality graphene on high-kappa dielectric SrTiO3
      substrates.
AB  - High-quality monolayer graphene was synthesized on high-kappa dielectric single
      crystal SrTiO3 (STO) substrates by a facile metal-catalyst-free chemical vapor
      deposition process. The as-grown graphene sample was suitable for fabricating a
      high performance field-effect transistor (FET), followed by a far lower operation
      voltage compared to that of a SiO2-gated FET and carrier motilities of
      approximately 870-1050 cm(2).V(-1).s(-1) in air at rt. The directly grown high
      quality graphene on STO makes it a perfect candidate for designing transfer-free,
      energy-saving, and batch production of FET arrays. 

PMID- 24746140
TI  - Convenient synthesis of triphenylphosphanylidene spiro[cyclopentane-1,3'
      indolines] and spiro[cyclopent[3]ene-1,3'-indolines] via three-component
      reactions. [Corrected].
AB  - Three-component reactions of triphenylphosphine, but-2-ynedioate, and isatylidene
      malononitrile (ethyl cyanoacetate) in dimethoxyethane resulted in
      triphenylphosphanylidene spiro[cyclopentane-1,3'-indolines] in satisfactory
      yields. Furthermore, similar three-component reactions of triphenylphosphine, hex
      2-en-4-ynedioate, and isatylidene malononitrile (ethyl cyanoacetate) afforded
      functionalized spiro[cyclopent[3]ene-1,3'-indolines] in good yields. [Corrected]

PMID- 24746142
TI  - Oxidative stretching of metal-metal bonds to their limits.
AB  - Oxidation of quadruply bonded Cr2(dpa)4, Mo2(dpa)4, MoW(dpa)4, and W2(dpa)4 (dpa
      = 2,2'-dipyridylamido) with 2 equiv of silver(I) triflate or ferrocenium triflate
      results in the formation of the two-electron-oxidized products [Cr2(dpa)4](2+)
      (1), [Mo2(dpa)4](2+) (2), [MoW(dpa)4](2+) (3), and [W2(dpa)4](2+) (4). Additional
      two-electron oxidation and oxygen atom transfer by m-chloroperoxybenzoic acid
      results in the formation of the corresponding metal-oxo compounds
      [Mo2O(dpa)4](2+) (5), [WMoO(dpa)4](2+) (6), and [W2O(dpa)4](2+) (7), which
      feature an unusual linear M...M=O structure. Crystallographic studies of the two
      electron-oxidized products 2, 3, and 4, which have the appropriate number of
      orbitals and electrons to form metal-metal triple bonds, show bond distances much
      longer (by >0.5 A) than those in established triply bonded compounds, but these
      compounds are nonetheless diamagnetic. In contrast, the Cr-Cr bond is completely
      severed in 1, and the resulting two isolated Cr(3+) magnetic centers couple
      antiferromagnetically with J/kB= -108(3) K [-75(2) cm(-1)], as determined by
      modeling of the temperature dependence of the magnetic susceptibility. Density
      functional theory (DFT) and multiconfigurational methods (CASSCF/CASPT2) provide
      support for "stretched" and weak metal-metal triple bonds in 2, 3, and 4. The
      metal-metal distances in the metal-oxo compounds 5, 6, and 7 are elongated beyond
      the single-bond covalent radii of the metal atoms. DFT and CASSCF/CASPT2
      calculations suggest that the metal atoms have minimal interaction; the
      electronic structure of these complexes is used to rationalize their
      multielectron redox reactivity. 

PMID- 24746141
TI  - Sociodemographic and socioeconomic patterns of chronic non-communicable disease
      among the older adult population in Ghana.
AB  - BACKGROUND: In Ghana, the older adult population is projected to increase from
      5.3% of the total population in 2015 to 8.9% by 2050. National and local
      governments will need information about non-communicable diseases (NCDs) in this
      population in order to allocate health system resources and respond to the health
      needs of older adults. DESIGN: The 2007/08 Study on global AGEing and adult
      health (SAGE) Wave 1 in Ghana used face-to-face interviews in a nationally
      representative sample of persons aged 50-plus years. Individual respondents were
      asked about their overall health, diagnosis of 10 chronic non-communicable
      conditions, and common health risk factors. A number of anthropometric and health
      measurements were also taken in all respondents, including height, weight, waist
      and hip circumferences, and blood pressure (BP). RESULTS: This paper includes
      4,724 adults aged 50-plus years. The highest prevalence of self-reported chronic
      conditions was for hypertension [14.2% (95% CI 12.8-15.6)] and osteoarthritis
      [13.8%, (95% CI 11.7-15.9)]. The figure for hypertension reached 51.1% (95% CI
      48.9-53.4) when based on BP measurement. The prevalence of current smokers was
      8.1% (95% CI 7.0-9.2), while 2.0 (95% CI 1.5-2.5) were infrequent/frequent heavy
      drinkers, 67.9% (95% CI 65.2-70.5) consume insufficient fruits and vegetables,
      and 25.7% (95% CI 23.1-28.3) had a low level of physical activity. Almost 10%
      (95% CI 8.3-11.1) of adults were obese and 77.6% (95% CI 76.0-79.2) had a high
      risk waist-to-hip ratio (WHR). Risks from tobacco and alcohol consumption
      continued into older age, while insufficient fruit and vegetable intake, low
      physical activity and obesity increased with increasing age. The patterns of risk
      factors varied by income quintile, with higher prevalence of obesity and low
      physical activity in wealthier respondents, and higher prevalence of insufficient
      fruit and vegetable intake and smoking in lower-income respondents. The
      multivariate analysis showed that only urban/rural residence and body mass index
      (BMI) were common determinates of both self-reported and measured hypertension,
      while all other determinants have differing patterns. CONCLUSIONS: The findings
      show a high burden of chronic diseases in the older Ghanaian population, as well
      as high rates of modifiable health risk factors. The government could consider
      targeting these health behaviors in conjunction with work to improve enrolment
      rates in the National Health Insurance Scheme.

PMID- 24746143
TI  - Isolation and structural elucidation of antioxidant peptides from oyster
      (Saccostrea cucullata) protein hydrolysate.
AB  - Protein derived from the oyster (Saccostrea cucullata) was hydrolyzed using
      protease from Bacillus cereus SU12 for isolation of antioxidant peptides. The
      oyster hydrolysate exhibited a strong antioxidant potential in DPPH (85.7+/
      0.37%) followed by Hydrogen peroxide radical scavenging activity (81.6+/-0.3%),
      Hydroxyl radical-scavenging activity (79.32+/-0.6%), Reducing power assay (2.63+/
      0.2 OD at 700nm). Due to the high antioxidant potential, hydrolysate was
      fractionated in Sephadex G-25 gel filtration chromatography. The active peptide
      fraction was further purified by UPLC-MS. Totally 7 antioxidant peptides were
      collected. Among 7 peptides (SCAP 1-7), 3 peptides (SCAP 1, 3 and 7) had highest
      scavenging ability on DPPH radicals. The amino acid sequence and molecular mass
      of purified antioxidant peptides (SCAP1, SCAP3 and SCAP7) were determined by Q
      TOF ESI mass spectroscopy and structures of the peptides were Leu-Ala-Asn-Ala-Lys
      (MW=515.29Da), Pro-Ser-Leu-Val-Gly-Arg-Pro-Pro-Val-Gly-Lys-Leu-Thr-Leu
      (MW=1432.89Da) and Val-Lys-Val-Leu-Leu-Glu-His-Pro-Val-Leu (MW=1145.75Da),
      respectively. The unique amino acid composition and sequence in the peptides
      might play an important role in expression of their antioxidant activity. The
      results of this study suggest that oyster protein hydrolysate is good source of
      natural antioxidants. 

PMID- 24746144
TI  - The role of P2X7 receptor in PC12 cells after exposure to oxygen-glucose
      deprivation.
AB  - Adenosine triphosphate (ATP) plays an important role in signal transmission via
      acting on P2X receptors. P2X7 receptor is involved in pathophysiological changes
      of ischemic diseases. The PC12 cell line is a popular model system to study
      sympathetic neuronal function. In this study, the effects of P2X7 on the
      viability or [Ca(2+)]i in PC12 cells after exposure to oxygen-glucose deprivation
      (OGD) were investigated. The results showed that the viability of PC12 cells was
      decreased under the condition of OGD. BzATP, a P2X7 agonist, decreased the
      viability, while P2X7 antagonist oxATP or P2X7 siRNA reversed the viability of
      PC12 cells under the condition of OGD. The expression levels of P2X7 mRNA and
      protein in PC12 cells were up-regulated under the condition of OGD or BzATP
      treatment. The expression levels of P2X7 mRNA and protein were significantly
      decreased in OGD PC12 cells, which were pretreated with oxATP or P2X7 siRNA. It
      was also found that oxATP or P2X7 siRNA effectively suppressed the increase of
      [Ca(2+)]i induced by OGD. P2X7 agonist ATP or BzATP enhanced the [Ca(2+)]i rise
      induced by OGD in PC12 cells. The [Ca(2+)]i peak induced by ATP or BzATP in OGD
      group was decreased by ERK inhibitor U0126. Therefore, P2X7 antagonists or P2X7
      siRNA could depress the sympathetic neuronal damage induced by ischemia. 

PMID- 24746146
TI  - Antibody humanization methods for development of therapeutic applications.
AB  - Recombinant antibody technologies are rapidly becoming available and showing
      considerable clinical success. However, the immunogenicity of murine-derived
      monoclonal antibodies is restrictive in cancer immunotherapy. Humanized
      antibodies can overcome these problems and are considered to be a promising
      alternative therapeutic agent. There are several approaches for antibody
      humanization. In this article we review various methods used in the antibody
      humanization process. 

PMID- 24746145
TI  - Ehrlichia and spotted fever group Rickettsiae surveillance in Amblyomma
      americanum in Virginia through use of a novel six-plex real-time PCR assay.
AB  - The population of the lone star tick Amblyomma americanum has expanded in North
      America over the last several decades. It is known to be an aggressive and
      nondiscriminatory biter and is by far the most common human-biting tick
      encountered in Virginia. Few studies of human pathogen prevalence in ticks have
      been conducted in our state since the mid-twentieth century. We developed a six
      plex real-time PCR assay to detect three Ehrlichia species (E. chaffeensis, E.
      ewingii, and Panola Mountain Ehrlichia) and three spotted fever group Rickettsiae
      (SFGR; R. amblyommii, R. parkeri, and R. rickettsii) and used it to test A.
      americanum from around the state. Our studies revealed a presence of all three
      Ehrlichia species (0-24.5%) and a high prevalence (50-80%) of R. amblyommii, a
      presumptively nonpathogenic SFGR, in all regions surveyed. R. parkeri, previously
      only detected in Virginia's Amblyomma maculatum ticks, was found in A. americanum
      in several surveyed areas within two regions having established A. maculatum
      populations. R. rickettsii was not found in any sample tested. Our study provides
      the first state-wide screening of A. americanum ticks in recent history and
      indicates that human exposure to R. amblyommii and to Ehrlichiae may be common.
      The high prevalence of R. amblyommii, serological cross-reactivity of all SFGR
      members, and the apparent rarity of R. rickettsii in human biting ticks across
      the eastern United States suggest that clinical cases of tick-borne disease,
      including ehrlichiosis, may be commonly misdiagnosed as Rocky Mountain spotted
      fever, and that suspicion of other SFGR as well as Ehrlichia should be increased.
      These data may be of relevance to other regions where A. americanum is prevalent.

PMID- 24746147
TI  - Synthesis and characterization of core-shell Au Fe oxide nanocomposites and their
      application for detecting immunological interaction.
AB  - Gold (Au) Fe oxide core-shell nanostructure is a major class of nanoscale
      materials that has attracted considerable attention due to its biotechnological
      and biomedical applications and properties. Here we synthesized magnetite
      nanoparticles (MNPs), an average size of 10-12 nm in diameter, using the chemical
      co-precipitation of Fe2(+) and Fe3(+) in strong alkaline material. Then, an Au
      coated Fe oxide core-shell nanocomposite with an average diameter of 18-20 nm was
      produced in the presence of sodium citrate as the reducing agent. The core-shell
      structure and the presence of the Fe and Au phases have been confirmed by
      transmission electron microscopy (TEM), x-ray diffraction (XRD), and Fourier
      transform infrared spectroscopy (FTIR). The Au-coated Fe oxide NPs can be used as
      a carrier in digoxin immunoassays. The concentration of anti-digoxin antibody
      (Ab) immobilized on the NPs was 30 MUg/mg. In order to validate the quality of
      the Au-coated Fe oxide NPs as immunoassay carriers, an immunoassay system was
      developed. The relative amount of anti-digoxin Ab immobilized on the NPs was
      determined by enzyme linked immunosorbent assay (ELISA). Immobilization studies
      with Ab demonstrated that the Au Fe oxide core-shell nanostructure can be used to
      immobilize Ab, making them valuable for biomedical and biological applications. 

PMID- 24746149
TI  - Establishment of a convenient sandwich-ELISA for direct quantification of
      glucosyltransferase-I: application for dual diagnosis of dental caries.
AB  - Previously, we established a convenient enzyme-linked immunosorbent assay (ELISA)
      system targeting glucosyltransferase (GTF)-B derived from Streptococcus mutans
      for diagnosing caries risk. However, it has been reported that S. sobrinus
      possesses high cariogenicity and is more frequently detected in highly caries
      susceptible patients than S. mutans is. S. sobrinus can secrete GTF-I, an
      important cariogenic factor for dental plaque formation, as well as S. mutans GTF
      B. Therefore, in this study, we developed another feasible ELISA system targeting
      S. sobrinus GTF-I that would ensure caries risk determination by combined GTF-I
      and GTF-B levels. A readily measurable sandwich-ELISA system was devised, which
      consisted of monoclonal and polyclonal antibodies against GTF-I. The developed
      sandwich-ELISA system quantified the purified GTF-I with sensitivity and
      specificity, and a positive correlation was observed between the amount of GTF-I
      extracted from clinical plaque samples and S. sobrinus levels. Furthermore, high
      levels of GTF-I and GTF-B were detected using the sandwich-ELISA system in caries
      susceptible subjects. These results indicate that the sandwich-ELISA system
      against GTF-I developed in this study is useful, and that the dual detection of
      the caries risk factors GTF-I and GTF-B is helpful for predicting caries risk. 

PMID- 24746148
TI  - Generating a battery of monoclonal antibodies against native green fluorescent
      protein for immunostaining, FACS, IP, and ChIP using a unique adjuvant.
AB  - Using a unique, nontoxic adjuvant compound of poly(I:C) and anti-CD40 MAb, a
      battery of eight mouse monoclonal antibodies was generated against native green
      fluorescent protein. All were effective to varying degrees for immunostaining
      paraformaldehyde-fixed cells, six for staining sections of paraffin-embedded
      tissue, all to varying degrees in fluorescent-activated cell sorting, five for
      immunoprecipitation, and seven for chromatin immunoprecipitation. None worked in
      denaturing Western blots since the target was the native GFP protein. Both the
      hybridomas and antibodies are available at cost through DSHB, a non-profit
      National Resource created by the National Institutes of Health. 

PMID- 24746150
TI  - Efficient generation of monoclonal antibodies against major structural proteins
      of rabies virus with suckling mouse brain antigen.
AB  - The rabies virus is a neurotropic virus that causes fatal disease in humans and
      animals. However, not all commercial antibodies against rabies virus (RABV)
      structural proteins are generally available, and production of high-quality
      monoclonal antibodies (MAbs) requires high purification of virus particles and
      special facilities and is time-consuming. By using RABV-infected suckling mouse
      brain as antigens in this study, 11 hybridoma cells secreting MAbs against RABV
      were obtained, which showed strong reactivity with RABV-infected Vero cells in
      immunofluorescence assay. Among the 11 MAbs, three MAbs (1B11, 1C8, and 8H12)
      showed a neutralizing effect to RABV, while MAb 4B7 recognized the recombinant
      nucleoprotein (N) of RABV expressed in Vero cells; seven MAbs (1H3, 3H7, 4E7,
      4G3, 5A10, 6C9, and 7B3) reacted specifically with phosphoprotein (P) of RABV.
      The MAbs developed in this study will be useful in establishing a diagnostic test
      and study on the interactions between RABV and its host. 

PMID- 24746151
TI  - Evaluation of immunodominant proteins of Mycobacterium avium paratuberculosis
      cell wall by Western blot analysis.
AB  - Mycobacterium avium subspecies paratuberculosis (M. paratuberculosis) is a slow
      growing mycobactin, whose dependence on mycobacterial species is known to be the
      causative agent of Johne's disease (paratuberculosis) in all species of domestic
      ruminants worldwide. The organism is transmitted via close contact, ingestion, or
      transplacentally from mother to fetus and occurs commonly in grazing domestic
      animals. Johne's disease (JD) is characterized by gradual weight loss, decreased
      milk production, and diarrhea due to the chronic, progressive, granulomatous
      enteritis and lymphadenitis. The disease can cause serious economic damage to the
      dairy industry due to the loss of milk production and early culling of infected
      animals. In recent years, researchers have focused on the identification of a
      specific antigen of M. paratuberculosis to use in diagnosis test and preparation
      of effective vaccine. The goal of this study is evaluation of the immunodominant
      proteins of M. paratuberculosis cell wall. The amount of protein was determined
      with a Lowry assay (22.68 MUg/100 MUL). For production of polyclonal antibody
      against proteins of M. paratuberculosis cell wall, a New Zealand white rabbit was
      immunized with antigen and Freund's adjuvant. After immunization, the rabbit was
      bled to produce enriched serum. Antibodies were purified from serum with ion
      exchange chromatography. In the Ouchterlony test, the reactions between antigen
      and antibodies were seen in dilutions of one quarter for serum, one quarter for
      Ig, and one half for IgG by clear precipitation lines due to the well
      immunization of the rabbit. Electrophoresis and Western blot analysis were used
      and subsequently a sharp band appeared in nitrocellulose paper; these bands were
      about 25, 37, 50, 75, and 150 kDa molecular weight, which indicated
      immunodominant proteins. 

PMID- 24746152
TI  - A mouse monoclonal antibody against Alexa Fluor 647.
AB  - Fluorophores are essential tools in molecular and cell biology. However, their
      application is mostly confined to the singular exploitation of their fluorescent
      properties. To enhance the versatility and expand the use of the fluorophore
      Alexa Fluor 647 (AF647), we generated a mouse monoclonal antibody against it. We
      demonstrate its use of AF647 for immunoblot, immunoprecipitation, and
      cytofluorimetry. 

PMID- 24746153
TI  - A novel monoclonal antibody against the constant region of goose immunoglobulin
      light chain.
AB  - A monoclonal antibody (MAb) against the antigenic determinant of the constant
      region of goose immunoglobulin light chain (GoIgCL) was produced and
      characterized for the first time here. Goose immunoglobulin (Ig) in serum was
      purified by immunoaffinity chromatography and the resulting protein was used as
      immunogen to immunize BALB/c mice. At the same time, the GoIgCL gene was
      expressed and purified as the screening antigen for selecting MAb against GoIgCL.
      One hybridoma that produces antibodies against GoIgCL was selected by indirect
      ELISA. Then the characterization of the MAb was analyzed by ELISA, Western blot,
      and flow cytometry. It was found to be IgG1 with kappa light chain; the MAB has
      high specificity to Ig in goose serum, bile, and B lymphocytes from peripheral
      blood, reacts only with the light chain of goose Ig, and can distinguish Ig from
      other birds. Therefore, the MAb generated in this study can be used as a specific
      reagent for detection of goose disease-specific antibodies and as a powerful tool
      for basic immunology research on geese. 

PMID- 24746154
TI  - Generation of a monoclonal antibody against the extracellular domain of IGF-1R.
AB  - Type I insulin-like growth factor receptor (IGF-1R) is a receptor tyrosine kinase
      that is involved in the transformation of cells, cancer proliferation, and
      metastatic events in various types of cancer. The present study reports on the
      generation of a mouse monoclonal antibody (MAb) to IGF-1R using the mouse lymph
      node method. MAb 1B1, which reacts specifically with the extracellular domain of
      IGF-1R, was obtained using flow cytometry (FCM) screening using MCF-7 cells.
      Using immunostaining, MAb 1B1 detected IGF-1R mainly on the plasma membrane of
      MCF-7 cells. MAb 1B1 would be useful in FCM and immunofluorescence assays to
      detect IGF-1R-expressing cells for basic and clinical research. 

PMID- 24746155
TI  - Development of monoclonal antibodies to interrogate functional domains and
      isoforms of FREM1 protein.
AB  - FREM1 was first identified as an extracellular matrix protein that is essential
      for the formation of the epithelial basement membrane during embryonic
      development. Recent studies have shown that FREM1 also modulates innate immunity
      through its isoform 2 splice variant protein, known as Toll-like/interleukin-1
      receptor regulator (TILRR). TILRR is a co-receptor that enhances pro-inflammatory
      IL-1R1 signal transduction. Our previous study identified the minor allele of a
      SNP, rs1552896, in the intronic region of FREM1 gene to be associated with
      natural resistance to HIV-1 infection in a subgroup of Kenyan sex workers in the
      Pumwani cohort. To study the role of FREM1 and its variants in differential
      susceptibility to HIV-1 infection, we generated a panel of 17 monoclonal
      antibodies against two recombinant proteins of FREM1, rspD and rspF. Epitope
      mapping using overlapping pin peptides showed that the monoclonal antibody (MAb)
      panel interrogated seven unique regions across five different domains, including
      the C-type lectin domain disulfide bond and the TILRR GAG serine attachment site.
      Utility of three selected FREM1 MAbs were demonstrated by FACS and
      immunohistochemical detection of FREM1 in 293F kidney embryonic cells, HeLa 229
      cervical cells, and Sup-T1 cells. Thus, these monoclonal antibodies could be used
      to study the functional domains of FREM1 and its isoforms. 

PMID- 24746161
TI  - A rare case of an aggressive osteoblastoma of the squamous temporal bone: a
      unique presentation with literature review.
AB  - Aggressive osteoblastoma is a rare osteoid tissue forming tumour commonly
      affecting the spine with predilection for the posterior elements. Calvarial
      involvement is extremely rare with only two reported cases in the literature. Due
      to its overlapping clinical, radiographic and histological features with
      ossifying fibroma, benign osteoblastoma and osteosarcoma, it is very difficult
      accurately to diagnose this lesion at an early stage. A rare case of an
      aggressive osteoblastoma of the squamous temporal bone in a young male is
      presented here which was misdiagnosed twice before reaching the final diagnosis
      by correlating clinical, radiographic and histopathological features. 

PMID- 24746162
TI  - A simplified version of the weight-bearing ankle lunge test: description and test
      retest reliability.
AB  - The purpose of this study was twofold: (1) to describe a new version of the
      weight-bearing ankle lunge test (WBLT) that is simple to administer, that allows
      clinicians and sports medicine practitioners to directly assess (in degrees) the
      ankle dorsiflexion range of motion in a very short period of time while adopting
      a comfortable testing position; as well as (2) to determine the test-retest
      reliability of the ankle dorsiflexion range of motion measure obtained from the
      new version of the WBLT. A total of 50 active adults completed this study. All
      participants performed the new version of the WBLT on three different occasions,
      with a two-week interval between testing sessions. Reliability was examined
      through the change in the mean between consecutive pairs of testing sessions
      (ChM), standard error of measurement (SEM), minimal detectable change at 95%
      confidence interval (MDC95), and intraclass correlation coefficient (ICC2,k). The
      findings showed negligible or trivial ChM values for all the flexibility measures
      analysed (<1 degrees ). Furthermore, the SEM and MDC95 scores for the ankle
      dorsiflexion measure were 1.3 and 3.8 respectively, and the ICC2k was 0.95.
      Therefore, this study demonstrated that the ankle dorsiflexion measure obtained
      from the new version of the WBLT has excellent test-retest reliability scores.
      Thus, an observed change larger than 3.8 degrees  from baseline scores after
      performing a treatment would indicate that a real change in ankle dorsiflexion
      range of motion was likely.

PMID- 24746163
TI  - Stereotype confirmation concern and fear of negative evaluation among African
      Americans and Caucasians with social anxiety disorder.
AB  - Fear of negative evaluation is a central component of social anxiety. The current
      study examines the relation between fear of negative evaluation and fears of
      confirming stereotypes about social groups to which one belongs among people
      diagnosed with social anxiety disorder. Participants (N=94) with a primary
      diagnosis of social anxiety disorder who self-identified as either African
      American (n=41) or Caucasian (n=53) completed standardized self-report measures
      of stereotype confirmation concerns and fear of negative evaluation. Results from
      hierarchical logistical regression showed that stereotype confirmation concerns
      predicted fear of negative evaluation for both racial groups, with greater
      concern predicting greater fear. This association was moderated by race, B=-.24,
      t=-2.67, p<.01, such that stereotype confirmation concerns had a stronger
      association with fear of negative evaluation for Caucasians (b=.38, p<.01) than
      for African Americans (b=.14, p<.05). This study is the first to directly examine
      the relation between stereotypes and fear of negative evaluation within a
      socially anxious sample. Although we cannot identify the specific social group to
      which each participant's stereotype confirmation concerns apply, this study
      provides quantitative evidence that the social context within which socially
      anxious individuals view themselves impacts their fear of negative evaluation and
      highlights the need for further research in this area. 

PMID- 24746168
TI  - A retrospective survey of quality of reporting on randomized controlled trials of
      metformin for polycystic ovary syndrome.
AB  - BACKGROUND: From previous reviews, there still have been controversies over the
      effect of metformin (MET) on reproductive function in PCOS patients. The reasons
      for the inconsistent findings especially lie in the transparency and accuracy of
      randomized controlled trials (RCTs) reports. However, we could find no data about
      the quality of RCTs reporting in MET for PCOS. Thus, a retrospective survey
      related to the quality of reporting in MET for PCOS was conducted. METHODS: A
      retrospective survey was conducted by two investigators. Two investigators
      assessed the quality of overall reporting and key methodological factors
      reporting using items from the CONSORT 2010 statement. RESULTS: A total of 39
      RCTs were included in full text. The median overall quality score was 9, with a
      minimum of 2 and a maximum of 13. Good or general reporting existed in 11 items
      with positive rate of more than or equal to 50%. The median score of key
      methodological items was 4 with a minimum of 0 and a maximum of 5. Randomization,
      allocation concealment, blinding, baseline characteristics and intention-to-treat
      (ITT) analysis were reported in 26 (67%), 19 (49%), 20 (51%), 38 (97%) and 17
      (44%) of the 39 RCTs, respectively. After adjustment, the mean overall score
      increased by about 1.71 for manuscripts with funding source (95% CI, 0.18 to
      3.24), while it increased by about 3.51 for manuscripts published in one year
      increment (95% CI, 1.82 to 5.19). There was a relatively close, significant
      correlation (r = 0.589, P < 0.001) between the score of overall reporting quality
      and year of publication. CONCLUSION: Although the overall reporting quality of
      RCTs in MET for PCOS has improved over time, reporting of key methodological
      items remains poor. Reporting of RCTs on MET for PCOS should keep up with the
      standards of the CONSORT statement.

PMID- 24746164
TI  - Glioma diagnostics and biomarkers: an ongoing challenge in the field of medicine
      and science.
AB  - Glioma is the most common brain tumor. For the more aggressive form,
      glioblastoma, standard treatment includes surgical resection, irradiation with
      adjuvant temozolomide and, on recurrence, experimental chemotherapy. However, the
      survival of patients remains poor. There is a critical need for minimally
      invasive biomarkers for diagnosis and as measures of response to therapeutic
      interventions. Glioma shed extracellular vesicles (EVs), which invade the
      surrounding tissue and circulate within both the cerebrospinal fluid and the
      systemic circulation. These tumor-derived EVs and their content serve as an
      attractive source of biomarkers. In this review, we discuss the current state of
      the art of biomarkers for glioma with emphasis on their EV derivation.

PMID- 24746169
TI  - [Endoscopically assisted decompression of the median nerve in the pronator and
      Kiloh-Nevin syndrome: Surgical technique].
AB  - STATE OF THE ART: The proximal median nerve compression syndrome includes the
      pronator teres and the Kiloh-Nevin syndrome. This article presents a new surgical
      technique of endoscopic assisted median nerve decompression. MATERIAL AND
      SURGICAL TECHNIQUE: Endoscopic scissor decompression of the median nerve is
      always performed under plexus anaesthesia. It includes 6 key steps documented in
      this article. We review the indications and limitations of the surgical
      technique. RESULTS: Since 2011, three clinical series have highlighted the
      advantages of this technique. Functional and subjective results are discussed. We
      also review the limitations of the technique and its potential for future
      development. CONCLUSION: Although clinical results after endoscopic assisted
      decompression of the median nerve appear excellent they still need to be compared
      with conventional techniques. Clinical studies are likely to develop primarily
      due to the mini-invasive nature of this new surgical technique.

PMID- 24746170
TI  - How to help gastroenterology patients help themselves: leveraging insights from
      behavioral economics.

PMID- 24746172
TI  - Particle size effects in the catalytic electroreduction of CO2 on Cu
      nanoparticles.
AB  - A study of particle size effects during the catalytic CO2 electroreduction on
      size-controlled Cu nanoparticles (NPs) is presented. Cu NP catalysts in the 2-15
      nm mean size range were prepared, and their catalytic activity and selectivity
      during CO2 electroreduction were analyzed and compared to a bulk Cu electrode. A
      dramatic increase in the catalytic activity and selectivity for H2 and CO was
      observed with decreasing Cu particle size, in particular, for NPs below 5 nm.
      Hydrocarbon (methane and ethylene) selectivity was increasingly suppressed for
      nanoscale Cu surfaces. The size dependence of the surface atomic coordination of
      model spherical Cu particles was used to rationalize the experimental results.
      Changes in the population of low-coordinated surface sites and their stronger
      chemisorption were linked to surging H2 and CO selectivities, higher catalytic
      activity, and smaller hydrocarbon selectivity. The presented activity-selectivity
      size relations provide novel insights in the CO2 electroreduction reaction on
      nanoscale surfaces. Our smallest nanoparticles (~2 nm) enter the ab initio
      computationally accessible size regime, and therefore, the results obtained lend
      themselves well to density functional theory (DFT) evaluation and reaction
      mechanism verification.

PMID- 24746171
TI  - Role of tropomodulin's leucine rich repeat domain in the formation of neurite
      like processes.
AB  - Actin dynamics is fundamental for neurite development; monomer depolymerization
      from pointed ends is rate-limiting in actin treadmilling. Tropomodulins (Tmod)
      make up a family of actin pointed end-capping proteins. Of the four known
      isoforms, Tmod1-Tmod3 are expressed in brain cells. We investigated the role of
      Tmod's C-terminal (LRR) domain in the formation of neurite-like processes by
      overexpressing Tmod1 and Tmod2 with deleted or mutated LRR domains in PC12 cells,
      a model system used to study neuritogenesis. Tmod1 overexpression results in a
      normal quantity and a normal length of processes, while Tmod2 overexpression
      reduces both measures. The Tmod2 overexpression phenotype is mimicked by
      overexpression of Tmod1 with the LRR domain removed or with three point mutations
      in the LRR domain that disrupt exposed clusters of conserved residues. Removal of
      Tmod2's LRR domain does not significantly alter the outgrowth of neurite-like
      processes compared to that of Tmod2. Overexpression of chimeras with the N
      terminal and C-terminal domains switched between Tmod1 and Tmod2 reinforces the
      idea that Tmod1's LRR domain counteracts the reductive effect of the Tmod N
      terminal domain upon formation of processes while Tmod2's LRR domain does not. We
      suggest that the TM-dependent actin capping ability of both Tmods inhibits the
      formation of processes, but in Tmod1, this inhibition can be controlled via its
      LRR domain. Circular dichroism, limited proteolysis, and molecular dynamics
      demonstrate structural differences in the C-terminal region of the LRR domains of
      Tmod1, Tmod2, and the Tmod1 mutant.

PMID- 24746173
TI  - Empagliflozin, a sodium glucose co-transporter 2 inhibitor, in the treatment of
      type 1 diabetes.
AB  - INTRODUCTION: Available anti-hyperglycemic therapy in type 1 diabetes (T1DM) is
      currently restricted to insulin, pramlintide, and pancreas or islet cell
      transplantation. The imperfect replication of normal insulin secretion and
      glucose control has been a driver for development of other anti-hyperglycemic
      agents for this population. Empagliflozin, a sodium glucose co-transporter 2
      (SGLT2) inhibitor, is currently under investigation as an add-on therapy to
      insulin in T1DM. AREAS COVERED: Within the drug evaluation, the authors describe
      the mechanism of action of SGLT2 inhibitors and preliminary results from studies
      investigating treatment in rodent models and in individuals with T1DM. EXPERT
      OPINION: Studies on adjunct therapeutic effects of empagliflozin in individuals
      with T1DM are limited, but initial reports show favorable effects on reducing
      HbA1c, body weight, total daily insulin dose and hypoglycemic events.
      Intriguingly, this drug may confer a degree of renal protection by reducing
      glomerular hyperfiltration that can arise in the diabetic state. Currently, the
      primary concern seems to be the presence of ketone levels indicating an under
      insulinized state. Long-term effects can only be inferred from studies in type 2
      diabetes mellitus at this time. Empagliflozin represents a novel non-insulin
      mediated therapy that warrants further investigation.

PMID- 24746175
TI  - Functional brain imaging: gatecrashing the clinical party?

PMID- 24746174
TI  - Diagnostic precision of PET imaging and functional MRI in disorders of
      consciousness: a clinical validation study.
AB  - BACKGROUND: Bedside clinical examinations can have high rates of misdiagnosis of
      unresponsive wakefulness syndrome (vegetative state) or minimally conscious
      state. The diagnostic and prognostic usefulness of neuroimaging-based approaches
      has not been established in a clinical setting. We did a validation study of two
      neuroimaging-based diagnostic methods: PET imaging and functional MRI (fMRI).
      METHODS: For this clinical validation study, we included patients referred to the
      University Hospital of Liege, Belgium, between January, 2008, and June, 2012, who
      were diagnosed by our unit with unresponsive wakefulness syndrome, locked-in
      syndrome, or minimally conscious state with traumatic or non-traumatic causes. We
      did repeated standardised clinical assessments with the Coma Recovery Scale
      Revised (CRS-R), cerebral (18)F-fluorodeoxyglucose (FDG) PET, and fMRI during
      mental activation tasks. We calculated the diagnostic accuracy of both imaging
      methods with CRS-R diagnosis as reference. We assessed outcome after 12 months
      with the Glasgow Outcome Scale-Extended. FINDINGS: We included 41 patients with
      unresponsive wakefulness syndrome, four with locked-in syndrome, and 81 in a
      minimally conscious state (48=traumatic, 78=non-traumatic; 110=chronic,
      16=subacute). (18)F-FDG PET had high sensitivity for identification of patients
      in a minimally conscious state (93%, 95% CI 85-98) and high congruence (85%, 77
      90) with behavioural CRS-R scores. The active fMRI method was less sensitive at
      diagnosis of a minimally conscious state (45%, 30-61) and had lower overall
      congruence with behavioural scores (63%, 51-73) than PET imaging. (18)F-FDG PET
      correctly predicted outcome in 75 of 102 patients (74%, 64-81), and fMRI in 36 of
      65 patients (56%, 43-67). 13 of 41 (32%) of the behaviourally unresponsive
      patients (ie, diagnosed as unresponsive with CRS-R) showed brain activity
      compatible with (minimal) consciousness (ie, activity associated with
      consciousness, but diminished compared with fully conscious individuals) on at
      least one neuroimaging test; 69% of these (9 of 13) patients subsequently
      recovered consciousness. INTERPRETATION: Cerebral (18)F-FDG PET could be used to
      complement bedside examinations and predict long-term recovery of patients with
      unresponsive wakefulness syndrome. Active fMRI might also be useful for
      differential diagnosis, but seems to be less accurate. FUNDING: The Belgian
      National Funds for Scientific Research (FNRS), Fonds Leon Fredericq, the European
      Commission, the James McDonnell Foundation, the Mind Science Foundation, the
      French Speaking Community Concerted Research Action, the University of
      Copenhagen, and the University of Liege.

PMID- 24746176
TI  - Use of adjuvant chemotherapy (CT) and radiotherapy (RT) in incompletely resected
      (R1) early stage Non-Small Cell Lung Cancer (NSCLC): a European survey conducted
      by the European Society for Medical Oncology (ESMO) young oncologists committee.
AB  - BACKGROUND: Early stage Non-Small Cell Lung Cancer (NSCLC) is potentially curable
      with surgery. ESMO guidelines recommend cisplatin-based adjuvant chemotherapy
      (CT) for completely resected stage II-III NSCLC. There is limited evidence for
      the use of adjuvant CT and/or radiotherapy (RT) in incompletely resected (R1)
      early stage NSCLC. MATERIALS AND METHODS: A European survey of thoracic
      oncologists was conducted to evaluate use of adjuvant CT and RT for R1-resected
      NSCLC and to identify factors influencing treatment decisions. Demographics and
      information on clinical stage, regimens, cycles planned, radiotherapy sites,
      multidisciplinary management and discussion about inconclusive evidence with the
      patient were collected. Univariate and multivariate analyses were performed.
      RESULTS: 768 surveys were collected from 41 European countries. 82.9% of
      participants were medical oncologists; 49.3% ESMO members; 37.1% based in
      University Hospitals; 32.6% practicing oncology for over 15 years and 81.4%
      active in research. 91.4% of participants prescribed adjuvant CT and mostly
      cisplatin/vinorelbine (81.2%) or cisplatin/gemcitabine (42.9%). 85% discussed
      limited clinical evidence with the patient. In the univariate analysis, a
      statistically significant association with CT prescription was found for medical
      oncology specialty (p<0.001), ESMO membership (p<0.001), activity in clinical
      research (p=0.002) and increased frequency of ESMO guidelines consultation (p for
      trend <0.001). 48.3% of participants prescribed adjuvant RT and its prescription
      were associated with radiation oncology specialty (p<0.001), not being an ESMO
      member (p<0.001), years practicing specialty (p for trend=0.001), workload of
      lung cancer patients (p for trend=0.027) and decreased frequency in consulting
      ESMO guidelines (p<0.001). In the multivariate analysis, medical oncology and
      radiation oncology were the best discriminator for prescription of adjuvant CT
      and RT, respectively. CONCLUSION: This survey demonstrates that adjuvant CT and
      RT are commonly used in clinical practice for R1-resected NSCLC despite limited
      evidence. Prospective trials are necessary to clarify optimal management in this
      setting.

PMID- 24746177
TI  - Aprepitant in patients with advanced non-small-cell lung cancer receiving
      carboplatin-based chemotherapy.
AB  - OBJECTIVES: Chemotherapy-induced nausea and vomiting (CINV) is an unanswered
      problem in cancer therapy. We evaluated the efficacy and safety of triple
      antiemetic therapy with aprepitant, a 5-hydroxytryptamine-3 (5-HT(3)) receptor
      antagonist, and dexamethasone in patients with advanced non-small-cell lung
      cancer (NSCLC) who received carboplatin-based first-line chemotherapy. METHODS:
      Chemotherapy-naive patients with NSCLC were enrolled in this randomized phase-II
      study. Patients were randomized to standard antiemetic therapy with a 5-HT(3)
      receptor antagonist and dexamethasone, and aprepitant add-on triple antiemetic
      therapy. The primary endpoint was the complete response rate (no vomiting and no
      rescue therapy) during the 120 h post-chemotherapy. RESULTS: A total of 134
      patients were assigned randomly to the aprepitant group or the control group. The
      aprepitant group and the control group showed an overall complete response rate
      of 80.3% (95% confidence interval (CI), 69.2-88.1%) and 67.2% (95% CI, 55.3
      77.2%; odds ratio (OR), 0.50; 95% CI, 0.22-1.10; p = 0.085), respectively. Among
      patients taking carboplatin and pemetrexed, adding aprepitant significantly
      improved the complete response rate in the overall phase (83.8% in the aprepitant
      group and 56.8% in the control group; OR, 0.26; 95% CI, 0.08-0.70; p < 0.01) and
      the delayed phase (86.5% in the aprepitant group and 59.1% in the control group;
      OR, 0.23; 95% CI, 0.07-0.65; p < 0.01). CONCLUSION: Carboplatin-based
      chemotherapy has considerable emetic potential. Triple antiemetic therapy with
      aprepitant, a 5-HT(3) receptor antagonist, and dexamethasone improved the control
      of CINV prevention in patients receiving carboplatin and pemetrexed chemotherapy.

PMID- 24746178
TI  - LAPTM4B polymorphism increases susceptibility to multiple cancers in Chinese
      populations: a meta-analysis.
AB  - BACKGROUND: Lysosome-associated protein transmembrane-4 beta (LAPTM4B) is a novel
      cancer-related gene. While recent studies have reported that the LAPTM4B
      polymorphism increased the susceptibility of several cancers, the results remain
      inconclusive. Therefore, we performed a meta-analysis to systematically summarize
      the possible association. RESULTS: The meta-analysis was conducted based on 17
      studies in Chinese populations, including 4160 cases and 4148 controls. The
      relevant studies were searched through electronic databases updated in November
      2013. The strength of association between the LAPTM4B polymorphism and
      susceptibility to multiple cancers was assessed by odds ratio (OR) and 95%
      confidence interval (95% CI).The meta-analysis results suggested that the LAPTM4B
      polymorphism was significantly associated with overall susceptibility to multiple
      cancers in all genetic models (*2 vs. *1, OR = 1.53, 95% CI = 1.37-1.70; *2/2 vs.
      *1/1, OR = 2.18, 95% CI = 1.72-2.75; *2/1 vs.*1/1, OR = 1.62, 95% CI = 1.41-1.86;
      *2/1 + *2/2 vs. *1/1, OR = 1.70, 95% CI = 1.47-1.97; *2/2 vs. *2/1 + *1/1, OR =
      1.76, 95% CI = 1.50-2.05). Further subgroup analysis revealed a significant
      association between the LAPTM4B polymorphism and cancer susceptibility in the
      subgroups stratified by control source, cancer type, histopathologic
      differentiation, and TNM stage. CONCLUSIONS: This meta-analysis indicated that
      the LAPTM4B *2 allele was associated with increasing risk of multiple cancers,
      tumor initiation and development.

PMID- 24746179
TI  - Breastfeeding: the hidden barrier in Cote d'Ivoire's quest to eliminate mother-to
      child transmission of HIV.
AB  - INTRODUCTION: Cote d'Ivoire has one of the worst HIV/AIDS epidemics in West
      Africa. This study sought to understand how HIV-positive women's life
      circumstances and interactions with the public health care system in Bouake, Cote
      d'Ivoire, influence their self-reported ability to adhere to antiretroviral
      prophylaxis during pregnancy. METHODS: Semistructured interviews were conducted
      with 24 HIV-positive women not eligible for antiretroviral therapy and five
      health care workers recruited from four public clinics in which prevention of
      mother-to-child transmission services had been integrated into routine antenatal
      care. RESULTS: Self-reported adherence to prophylaxis is high, but women struggle
      to observe (outdated) guidelines for rapid infant weaning. Women's positive
      interactions with health providers, their motivation to protect their infants and
      the availability of free antiretrovirals seem to override most potential barriers
      to prophylaxis adherence. CONCLUSIONS: This study reveals the importance of
      considering the full continuum of prevention of mother-to-child transmission
      interventions, including infant feeding, instead of focussing primarily on
      prophylaxis for the mother and newborn.

PMID- 24746180
TI  - Transmitted drug resistance to rilpivirine among antiretroviral-naive patients
      living with HIV from northern Poland.
AB  - INTRODUCTION: Rilpivirine (RPV) is a second-generation non-nucleoside reverse
      transcriptase inhibitor (NNRTI) that was recently approved for the treatment of
      antiretroviral-naive individuals with HIV-1 viral load of <100,000 copies/ml. As
      transmission of the drug resistance mutations to this NNRTI may affect treatment
      outcomes, the frequency of primary, RPV-associated drug resistance mutations was
      assessed in this study. METHODS: For the study, 244 viral genome sequences from
      antiretroviral-naive individuals were obtained by bulk sequencing. RPV-associated
      mutations were divided into RPV resistance mutations (K101E/P, E138A/G/K/Q/R,
      V179L, Y181C/I/V, Y188L, H221Y, F227C and M230I/L) according to the International
      AIDS Society-USA (IAS-USA) mutation list and variants potentially affecting RPV
      susceptibility (L100I, K101H/T, E138S, V179F/D/G/T, G190A/E/S, F227L and M230V)
      based on the in vitro and in vivo data. RESULTS: IAS-USA RPV drug resistance
      mutations were found in 5.3% sequences, with E138A and E138G being the most
      common (3.7 and 0.8%, respectively), followed by K101E (0.4%) and Y181C (0.4%),
      with no significant differences in the frequency between subtype B and non-B
      clades. Mutations potentially reducing RPV susceptibility were found in 2.5% of
      sequences, and they included V179D (1.6%) and G190A (0.8%), with equal
      distribution among non-B (n=2, 2.5%) and subtype B (n=4, 2.5%) clades. Clustering
      of RPV mutations was infrequent. CONCLUSIONS: Prevalence of RPV-associated drug
      resistance mutations was low in the analysed sample and did not vary across the
      subtypes. The frequency of variants with potential influence on RPV
      susceptibility was similar among non-B variants if compared to B clades.
      Transmitted drug resistance to RPV is uncommon, which makes this a good option
      for the treatment of ARV-naive patients; however, genotype resistance testing
      should remain compulsory before starting an RPV-based regimen.

PMID- 24746183
TI  - Editorial for the virtual issue on inorganic cages and containers.

PMID- 24746182
TI  - Comparison of complete genome sequences of Usutu virus strains detected in Spain,
      Central Europe, and Africa.
AB  - The complete genomic sequence of Usutu virus (USUV, genus Flavivirus, family
      Flaviviridae) strain MB119/06, detected in a pool of Culex pipiens mosquitoes in
      northeastern Spain (Viladecans, Catalonia) in 2006, was determined and analyzed.
      The phylogenetic relationship with all other available complete USUV genome
      sequences was established. The Spanish sequence investigated showed the closest
      relationship to the USUV prototype strain SA AR 1776 isolated in South Africa in
      1959 (96.9% nucleotide and 98.8% amino acid identities). Conserved structural
      elements and enzyme motifs of the putative polyprotein precursor were identified.
      Unique amino acid substitutions were recognized; however, their potential roles
      as virulence markers could not be verified. Comparisons of the polyprotein
      precursor sequences of USUV strains detected in mosquitoes, birds, and humans
      could not confirm the predicted role of unique amino acid substitutions in
      relation to virulence in humans. Phylogenetic analysis of a partial coding
      section of the NS5 protein gene region indicated that USUV strains circulating in
      Europe form three different genetic clusters. Broad and targeted surveys for USUV
      in mosquitoes could reveal further details of the geographic distribution and
      genetic diversity of the virus in Europe and in Africa.

PMID- 24746181
TI  - L1CAM promotes enrichment of immunosuppressive T cells in human pancreatic cancer
      correlating with malignant progression.
AB  - Regulatory T cell (T-reg) enrichment in the tumor microenvironment is regarded as
      an important mechanism of tumor immune escape. Hence, the presence of T-regs in
      highly malignant pancreatic ductal adenocarcinoma (PDAC) is correlated with short
      survival. Likewise, the adhesion molecule L1CAM is upregulated during PDAC
      progression in the pancreatic ductal epithelium also being associated with poor
      prognosis. To investigate whether L1CAM contributes to enrichment of T-regs in
      PDAC, human CD4(+)CD25(+)CD127(-)CD49d(-) T-regs and CD4(+)CD25(-) T-effector
      cells (T-effs) were isolated by magnetic bead separation from blood of healthy
      donors. Their phenotype and functional behavior were analyzed in dependence on
      human premalignant (H6c7) or malignant (Panc1) pancreatic ductal epithelial
      cells, either exhibiting or lacking L1CAM expression. T cells derived from blood
      and tumors of PDAC patients were analyzed by flow cytometry and findings were
      correlated with clinical parameters. Predominantly T-regs but not T-effs showed
      an increased migration on L1CAM expressing H6c7 and Panc1 cells. Whereas
      proliferation of T-regs did not change in the presence of L1CAM, T-effs
      proliferated less, exhibited a decreased CD25 expression and an increased
      expression of CD69. Moreover, these T-effs exhibited a regulatory phenotype as
      they inhibited proliferation of autologous T cells. Accordingly, CD4(+)CD25(
      )CD69(+) T cells were highly abundant in PDAC tissues compared to blood being
      associated with nodal invasion and higher grading in PDAC patients. Overall,
      these data point to an important role of L1CAM in the enrichment of
      immunosuppressive T cells in particular of a CD4(+)CD25(-)CD69(+)-phenotype in
      PDAC providing a novel mechanism of tumor immune escape which contributes to
      tumor progression.

PMID- 24746184
TI  - Editorial on Correlative Microscopy.

PMID- 24746185
TI  - Mapping the broad CMY subtractive primary color gamut using a dual-active
      electrochromic device.
AB  - Although synthetic efforts have been fruitful in coarse color control, variations
      to an electrochromic polymer (ECP) backbone are less likely to allow for the fine
      control necessary to access the variations and shades of color needed in display
      applications. Through the use of thin films of cyan, magenta, and yellow ECPs,
      non-emissive subtractive color mixing allows the color of an electrochromic
      device (ECD) to be selected and tailored, increasing access to various subtle
      shades and allowing for a non-emissive display to exhibit a wide range of colors.
      Using a dual-active ECD, subtractive color mixing utilizing the cyan-magenta
      yellow (CMY) primary system was examined. The bounds of the gamut, or the subset
      of accessible colors, using these three 3,4-propylenedioxythiophene (PProDOT)
      derived materials in combination with the recently recognized 3,4
      propylenedioxypyrrole-based minimally color changing polymer (MCCP) were mapped,
      highlighting the benefit of applying subtractive color mixing toward the
      development of full-color non-emissive displays. Here, we demonstrate that ECPs
      are suitable for the generation of a wide gamut of colors through secondary
      mixing when layered as two distinct films, exhibiting both vibrantly colored and
      highly transmissive states. 

PMID- 24746186
TI  - Here come the newcomer granules, better late than never.
AB  - Exocytosis in pancreatic beta-cells employs Munc18/soluble N-ethylmaleimide
      sensitive factor attachment protein receptor (SNARE) complexes that mediate the
      priming and docking onto the plasma membrane (PM) of insulin granules, called
      predocked granules, that sit on the PM until Ca(2+) influx evokes fusion. This
      accounts for most of the initial peak secretory response. However, the subsequent
      sustained phase of glucose-stimulated insulin secretion arises from newcomer
      granules that have a minimal residence time at the PM before fusion. In this
      Opinion I discuss recent work that has begun to decipher the components of the
      exocytotic machinery of newcomer granules, including a Munc18/SNARE complex that
      is different from that mediating the fusion of predocked granules and which can
      potentially rescue defective insulin secretion in diabetes. These insights are
      applicable to other neuroendocrine cells that exhibit sustained secretion. 

PMID- 24746187
TI  - Enhancing the efficacy of innate immune agonists: could nanolipoprotein particles
      hold the key?

PMID- 24746188
TI  - CuS nanoparticles: clinically favorable materials for photothermal applications?

PMID- 24746189
TI  - Autophagy inhibition strategy for advanced nanomedicine.

PMID- 24746190
TI  - Novel biosensor may be an important step towards diagnosing early-stage
      Parkinson's disease.

PMID- 24746192
TI  - pH-sensitive polymeric nanoparticles for tumor-targeting doxorubicin delivery:
      concept and recent advances.
AB  - Doxorubicin is a potent chemotherapeutic drug applied in the clinics for the
      treatment of various human cancers. It is typically administered as the
      hydrochloride salt or in liposomal forms, which are plagued with severe side
      effects. In recent years, pH-sensitive polymeric nanoparticles that are capable
      of retaining drug during circulation while actively releasing it at the tumor
      site and/or inside the target tumor cells have received an overwhelming interest
      for tumor-targeting cancer chemotherapy. This smart delivery approach has shown
      to elegantly resolve the in vivo stability versus intracellular drug release
      dilemma, as well as stealth versus tumor cell uptake dilemma. In this review, the
      concept and exciting new advances in pH-sensitive polymeric nanoparticles for
      doxorubicin delivery are presented and discussed.

PMID- 24746193
TI  - Harnessing the potential of lipid-based nanomedicines for type-specific ovarian
      cancer treatments.
AB  - Epithelial ovarian cancers are a group of at least five histologically and
      clinically distinct diseases, yet at this time patients with these different
      diseases are all treated with the same platinum and taxane-based chemotherapeutic
      regimen. With increased knowledge of histotype-specific differences that
      correlate with treatment responses and resistance, novel treatment strategies
      will be developed for each distinct disease. Type-specific or resistance-driven
      molecularly targeted agents will provide some specificity over traditional
      chemotherapies and it is argued here that nanoscaled drug delivery systems, in
      particular lipid-based formulations, have the potential to improve the delivery
      and specificity of pathway-specific drugs and broad-spectrum cytotoxic
      chemotherapeutics. An overview of the current understanding of ovarian cancers
      and the evolving clinical management of these diseases is provided. This overview
      is needed as it provides the context for understanding the current role of drug
      delivery systems in the treatment of ovarian cancer and the need to design
      formulations for treatment of clinically distinct forms of ovarian cancer.

PMID- 24746194
TI  - Biocompatible surface-enhanced Raman scattering nanotags for in vivo cancer
      detection.
AB  - The advancement of surface-enhanced Raman scattering (SERS) is significantly
      increasing as an ultra-sensitive sensing technology in biomedical research. In
      this review, we focus on the most recent developments of biocompatible nanoprobes
      for cancer research. First, we discuss coating approaches to enhance the
      biocompatibility of SERS substrate and Raman reporters. Furthermore, interesting
      ligands such as antibodies, aptamers and polypeptides are attached to the surface
      of nanotags for targeting the cancerous cells in vitro. The unique multiplexing
      capabilities of the SERS technique have been applied for simultaneous multiple
      target recognition. Finally, these noninvasive, ultrasensitive tools are mostly
      highlighted for in vivo tumor detection. Potential application of SERS nanotags
      in therapeutic study and the possibility of SERS nanotags in biomedical
      applications are outlined briefly in this review.

PMID- 24746195
TI  - Regulation and dysregulation of tumor necrosis factor receptor-1.
AB  - TNF is an essential regulator of the immune system. Dysregulation of TNF plays a
      role in the pathology of many auto-immune diseases. TNF-blocking agents have
      proven successful in the treatment of such diseases. Development of novel, safer
      or more effective drugs requires a deeper understanding of the regulation of the
      pro-inflammatory activities of TNF and its receptors. The ubiquitously expressed
      TNFR1 is responsible for most TNF effects, while TNFR2 has a limited expression
      pattern and performs immune-regulatory functions. Despite extensive knowledge of
      TNFR1 signaling, the regulation of TNFR1 expression, its modifications,
      localization and processing are less clear and the data are scattered. Here we
      review the current knowledge of TNFR1 regulation and discuss the impact this has
      on the host. 

PMID- 24746196
TI  - EGFR expression in vulvar cancer: clinical implications and tumor heterogeneity.
AB  - Epidermal growth factor receptor (EGFR) protein expression was assessed by
      immunohistochemistry (IHC) in 150 cases of invasive vulvar squamous cell
      carcinoma. In addition, gene copy number status by fluorescence in situ
      hybridization was performed in a smaller set of samples. Results were correlated
      with patient's clinical data and prognostic factors. EGFR overexpression (2+ and
      3+) was observed on the membrane in 24.66% and 21.33% of all cases, respectively.
      Higher EGFR expression was associated with depth of invasion (P = .0409) and
      disease recurrence (P = .0401). Cytoplasm staining was found in 21.33% of the
      cases and was associated with absence of nodal metastasis (P = .0061) and better
      survival (P = .0199). Intratumor heterogeneity of EGFR IHC staining was
      frequently observed (55.33%) and was associated with the presence of nodal
      metastasis (P = .0207) and tumor invasion (P = .0161). Worse survival outcomes
      have been demonstrated in tumors with EGFR heterogeneity (P = .0434). EGFR gene
      status evaluated by fluorescence in situ hybridization did not correlate with
      protein expression evaluated by IHC. In conclusion, EGFR cytoplasm staining has
      no link with poorer outcome; still, this pattern of staining is even more related
      to better prognosis. EGFR heterogeneity of staining correlated with more
      aggressive tumors, and presented to be an important marker of poor prognosis in
      vulvar squamous cell carcinoma. The usage of small biopsies or even tissue
      microarrays for vulvar cancer evaluation should be carefully reconsidered for the
      assessment of EGFR as the results may be misleading. Protein overexpression may
      be independent on gene amplification, showing that other molecular mechanisms
      than copy number variation may regulate protein expression of EGFR in vulvar
      cancer. 

PMID- 24746198
TI  - BRAF genetic heterogeneity in papillary thyroid carcinoma and its metastasis.
AB  - Intratumoral heterogeneity is widely recognized as an important determinant of a
      cancer's initial response and its subsequent resistance to targeted therapy. BRAF
      V600E mutation, common in papillary thyroid carcinoma (PTC), is helpful in fine
      needle aspiration diagnosis of thyroid nodules and is being evaluated for
      targeted therapies. This study was designed to assess the presence of BRAF
      mutation heterogeneity within primary PTCs and between paired primary and
      metastatic lesions. Genetic heterogeneity was evaluated in 47 PTCs (38
      differentiated papillary thyroid carcinomas and 9 poorly differentiated PTCs with
      anaplastic areas). The differentiated papillary thyroid carcinomas included 16
      cases with regional lymph node metastases at thyroidectomy and 9 cases with
      recurrent metastases to regional lymph nodes more than 5 years post
      thyroidectomy. Genetic heterogeneity of BRAF was studied by comparing the
      mutation status in different samples of tumor as follows: (a) 2 separate areas
      (each >1.5 cm in diameter) within the primary tumor, (b) a more than 1.5 cm area
      of primary carcinoma and a second 5 mm area simulating a fine needle aspiration
      sample from a different portion of the primary tumor, (c) primary carcinoma and
      its lymph node metastasis at thyroidectomy, (d) primary carcinoma and the
      recurrent metastasis, and (e) differentiated and anaplastic areas in the primary
      carcinoma. BRAF mutation status was concordant in 95.2% of the 62 paired samples.
      Discordant BRAF status was detected in only 4.8% of the pairs studied and most
      frequently involved cases with recurrent metastasis thus suggesting a need for
      additional testing of these lesions before instituting therapy. 

PMID- 24746197
TI  - The utility of a novel triple marker (combination of TTF1, napsin A, and p40) in
      the subclassification of non-small cell lung cancer.
AB  - In lung cancer, targeted therapies depend on accurate histological
      subclassification of the tumor. The majority of lung cancers can be subclassified
      based on hematoxylin and eosin staining; however, classification may be difficult
      in small biopsies. In this study, we investigated the utility of a newly
      developed triple marker (combination of TTF1/Napsin A/p40) and compared the
      sensitivity and specificity of this novel marker with individual markers in the
      subclassification of non-small cell lung carcinomas. Lung cancer tissue
      microarrays were constructed using surgical resection material from the Johns
      Hopkins Hospital. They included 77 adenocarcinomas (ADCs), 77 squamous cell
      carcinomas (SqCCs), and 46 cases of metastatic lung ADCs. Immunostaining patterns
      of all markers were scored semi-quantitatively and compared. In ADCs, the
      sensitivity and specificity of the triple marker were 93.5% and 77.5%,
      respectively. The sensitivity and specificity of TTF1 and Napsin A were 85.7% and
      75.0%, and 89.6% and 90.0%. In SqCCs, the sensitivity and specificity of the
      triple marker were 88.3% and 92.5%, while the p40, p63 and CK5/6 showed 80.5% and
      90.0%; 93.5% and 80.0%; and 89.6% and 80.0%. In addition, the sensitivity and
      specificity of the triple marker in metastatic ADCs showed 71.7% and 73.5%,
      respectively. Our triple marker (combination of TTF1/Napsin A/p40) showed a
      similar sensitivity and specificity for the subclassification of NSCLC when
      compared to individual markers. Our study not only demonstrates a useful
      combination of immunomarkers but also optimally conserves tissue for molecular
      marker testing. 

PMID- 24746199
TI  - The FOXO1-miR27 tandem regulates myometrial invasion in endometrioid endometrial
      adenocarcinoma.
AB  - Micro-RNA (miRNA) signatures influence the prognosis of cancer, but little is
      known about their role in myometrial invasion in endometrioid endometrial
      adenocarcinoma (EEC). We studied miRNA expression signatures in noninvasive and
      invasive EEC focusing on the alteration of miR-27 and its main target, FOXO1 as
      well as their relationship with the clinicopathological parameters and other
      genetic alterations such as PIK3CA mutations. In 25 tumors and 5 normal
      endometria, unsupervised hierarchical clustering analysis showed that normal
      endometria and noninvasive EEC were grouped together and separately from invasive
      and advanced stage tumors. Of the 20 miRNAs differentially expressed in
      noninvasive (stage IA) and myoinvasive adenocarcinomas (stage IB and IC), miR27
      was overexpressed in invasive adenocarcinomas, and its expression increased
      linearly according to stage. Results were validated by quantitative real-time
      reverse transcription polymerase chain reaction in an independent series of 44
      EEC. By in situ hybridization, miR-27 expression was limited to the stroma. Using
      quantitative real-time reverse transcription polymerase chain reaction, the
      expression of proapoptotic transcription factor FOXO1 was down-regulated in
      invasive compared with noninvasive tumors. Furthermore, we found that the
      expression of active caspase 3 was higher in noninvasive than invasive EEC. When
      stratified by PIK3CA mutations, all invasive tumors down-regulated FOXO1, but
      only nonmutated adenocarcinomas showed miR-27 overexpression. In conclusion, we
      propose that the miR27-FOXO1 tandem inhibits apoptosis and represents an
      alternative pathway for tumor cell survival in PIK3CA-nonmutated EEC. 

PMID- 24746200
TI  - Support for p63 expression as an adverse prognostic marker in Merkel cell
      carcinoma: report on a Canadian cohort.
AB  - Recent evidence has invoked immunohistochemical expression of p63 in Merkel cell
      carcinoma as an adverse prognostic factor. Conflicting data led us to evaluate
      this. An Eastern Canadian cohort diagnosed between 1990 and 2012 was studied.
      Demographic and clinical data were obtained from pathology records and Provincial
      Cancer Registries. Pathological features were evaluated by the investigators.
      Merkel cell polyomavirus status was known in a subset of cases.
      Clinicopathological features were correlated with overall survival. The cohort
      consisted of 83 patients (mean age, 75.8 +/- 11.7 years) with a male/female ratio
      of 1.24:1. In a mean follow-up period of 175 weeks (+/-177), 51 patients died
      (61.4%). Of several parameters examined, 6 showed significant adverse
      associations with survival on univariate analysis: age (hazard ratio [HR], 1.05
      [1.02-1.08]), clinical stage (III/IV versus I/II; HR, 2.24 [1.18-4.27]), tumor
      size (HR, 1.16 [1.05-1.28]), combined versus pure morphology (HR, 1.82 [1.04
      3.18]), minimal tumor-infiltrating lymphocytes (HR, 2.23 [1.04-4.78]), and
      expression of p63 (positive in 49.4%; HR, 1.93 [1.09-3.43]). In the stage I/II
      subgroup, p63 expression was associated with a trend toward poor survival. On
      multivariate analysis, p63 expression was not significantly associated with
      reduced survival. Our data support existing evidence that p63 expression in
      Merkel cell carcinoma carries adverse implications for survival. That it was not
      an independent prognostic factor may be due to study size and/or its potential as
      a confounding variable with clinical stage. Of clinical importance is its
      association with a trend toward a poor outcome in early stage disease. 

PMID- 24746201
TI  - Hepatocellular adenomas in a large community population, 2000 to 2010:
      reclassification per current World Health Organization classification and results
      of long-term follow-up.
AB  - The data used for the World Health Organization classification of hepatocellular
      adenoma (HCA) is largely based on cases from tertiary level centers in Europe.
      This study examines the distribution of HCA subtypes in a large community
      population and determines the impact of immunohistochemistry (IHC) on
      reclassification, diagnosis, and management. All cases diagnosed as HCA in a
      large community hospital network from 2000 to 2010 were reviewed. The following
      immunohistochemical stains were evaluated in cases where paraffin-embedded tissue
      was available (n = 35): beta-catenin, glutamine synthetase, serum amyloid A, C
      reactive protein, liver fatty acid binding protein. Twenty-eight of 35 cases were
      confirmed to be HCA, 5 cases were reclassified as well-differentiated
      hepatocellular carcinoma, and 2 cases were reclassified as focal nodular
      hyperplasia. The HCA cases were further subclassified into hepatocyte nuclear
      factor 1alpha inactivated (29%), inflammatory (32%), inflammatory with beta
      catenin activation (3%), noninflammatory beta-catenin activated (0%), and
      unclassified (36%). Long-term follow-up was available on 33 of 35 cases, and
      there were no cases of recurrence or distant metastasis. IHC can provide a
      definite HCA subtype in two-thirds of cases. HCA subtypes in this large community
      based population differed from the prior large French studies, in that there were
      a greater proportion of unclassified adenomas and a virtual absence of beta
      catenin-activated adenomas. It is likely that most beta-catenin-activated
      hepatocellular tumors show morphologic and reticulin staining abnormalities
      indicative of well-differentiated hepatocellular carcinoma. IHC for glutamine
      synthetase and serum amyloid A can identify cases with beta-catenin activation
      and aid in the distinction of inflammatory adenoma and focal nodular hyperplasia.

PMID- 24746202
TI  - Activation of the Akt/mammalian target of rapamycin pathway in myxofibrosarcomas.
AB  - The Akt/mammalian target of rapamycin (mTOR) pathway plays important roles in
      modulating cellular function in response to extracellular signals such as growth
      factors and cytokines. The Akt/mTOR signaling pathway is activated in certain
      kinds of sarcomas. Myxofibrosarcoma is a soft tissue sarcoma, characterized by
      abundant myxoid stroma and frequent local recurrence. Here, we conducted a large
      scale examination of the clinicopathological and activation statuses of the
      Akt/mTOR pathways in myxofibrosarcoma. The phosphorylation status of Akt, mTOR,
      S6 ribosomal protein, and the eukaryotic translation initiation factor 4E-binding
      protein, and mitogen-activated protein kinase were assessed by
      immunohistochemistry in 101 formalin-fixed, paraffin-embedded samples, including
      68 primary tumors in myxofibrosarcoma. Immunohistochemical expressions were
      confirmed by Western blotting with 20 frozen samples, which were paired with
      normal tissue samples. PIK3CA and AKT1 gene mutations were also analyzed using 12
      primary tumor frozen samples. Immunohistochemically, phosphorylations of Akt,
      mTOR, S6 ribosomal protein, 4E-binding protein, and mitogen-activated protein
      kinase 1/2 were observed in 64.7%, 45.6%, 42.6%, 63.2%, and 64.7% of samples.
      Phosphorylated Akt/mTOR pathway proteins were correlated with one another and
      were also correlated with the phosphorylation of these proteins in the concordant
      recurrent tumors. Immunoblotting showed a high degree of phosphorylation in tumor
      samples, compared with that in normal tissue samples. Activation of the Akt/mTOR
      pathway was correlated with histologic grade and tumor progression. Mutational
      analysis failed to reveal any PIK3CA or AKT1 mutations around the hot spots.
      Activation of the Akt/mTOR pathway was associated with histologic malignancy and
      tumor progression in primary and recurrent myxofibrosarcoma. 

PMID- 24746203
TI  - Validation study of the Esohisto consensus guidelines for the recognition of
      microscopic esophagitis (histoGERD Trial).
AB  - In patients with gastroesophageal reflux disease (GERD), histology is generally
      believed to be a tool of limited diagnostic value. Our study aimed to assess the
      prevalence of microscopic esophageal lesions as defined by the Esohisto consensus
      guidelines, which have proven high interobserver agreement in previous studies.
      In the prospective Central European multicenter histoGERD trial, we recruited
      1071 individuals (576 females and 495 males; median age, 53 years; range, 15-93
      years) undergoing gastroscopy for nonselected reasons. Biopsy material was
      systematically sampled from above and below the gastroesophageal junction.
      Overall, histologic diagnosis of mild and severe esophagitis was made in 423
      (39.5%) and 296 (27.6%) individuals, respectively, whereas the squamous mucosa of
      352 individuals (32.9%) was normal upon histology or showed only insignificant
      findings. Proliferative changes of the squamous epithelium, in particular basal
      cell layer hyperplasia, papillary elongation, and intercellular space dilation,
      were more common than inflammatory cell infiltration. The presence of microscopic
      esophagitis was associated with male sex (P = .009), patients' symptoms (P =
      .003), history of proton pump inhibitor intake (P < .001), and the endoscopic
      diagnosis of esophagitis (P < .001). Notably, among the 450 patients with no
      endoscopic signs of esophagitis (Los Angeles Category N), 41.8% and 17.1% were
      identified with mild and severe (microscopic) esophagitis, respectively,
      indicating higher sensitivity of histologic diagnosis. In conclusion, our data
      illustrate the value of histology in the workup of patients with reflux disease.
      We suggest that biopsies should routinely be obtained when patients undergo upper
      gastrointestinal endoscopy for evaluation of GERD and may particularly be
      beneficial in patients with nonerosive reflux disease. 

PMID- 24746204
TI  - Morphologic and GATA1 sequencing analysis of hematopoiesis in fetuses with
      trisomy 21.
AB  - Trisomy 21 alters fetal liver hematopoiesis and, in combination with somatic
      globin transcription factor 1 (GATA1) mutations, leads to development of
      transient myeloproliferative disease in newborns. However, little is known about
      the morphological hematopoietic changes caused by trisomy 21 in the fetus, and to
      date, the exact onset of GATA1 mutations remains uncertain. Therefore, we
      analyzed fetal liver hematopoiesis from second trimester pregnancies in trisomy
      21 and screened for GATA1 mutations. We examined 57 formalin-fixed and paraffin
      embedded fetal liver specimens (49 harboring trisomy 21 and 8 controls) by
      immunohistochemistry for CD34, CD61, factor VIII, and glycophorin A. GATA1 exon 2
      was sequenced in fetal livers and corresponding nonhematologic tissue. Cell
      counts of megakaryocytes (P = .022), megakaryocytic precursors (P = .021), and
      erythroid precursors were higher in trisomy 21 cases. CD34-positive hematopoietic
      blasts showed no statistically significant differences. No mutation was detected
      by GATA1 exon 2 sequencing in fetal livers from 12 to 25 weeks of gestation. Our
      results suggest that GATA1 exon 2 mutations occur late in trisomy 21 fetal
      hematopoiesis. However, trisomy 21 alone provides a proliferative stimulus of
      fetal megakaryopoiesis and erythropoiesis. CD34-positive precursor cells are not
      increased in trisomy 21 fetal livers. 

PMID- 24746205
TI  - The expression of FOXL2 in pancreatic, hepatobiliary, and renal tumors with
      ovarian-type stroma.
AB  - FOXL2, a gene encoding a member of the fork-head-winged-helix family of
      transcription factors, is one of the earliest expressed genes during female
      gonadal development. It is expressed in normal ovarian stroma and ovarian
      neoplasms with granulosa cell lineage. Nonovarian tumors such as pancreatic
      mucinous cystic neoplasms (PMCs), hepatobiliary cystadenomas (HBCs), and mixed
      epithelial and stromal tumor of the kidney (MEST) have ovarian-type stroma.
      Immunohistochemical staining with FOXL2, estrogen receptor, and progesterone
      receptor was performed on 21 PMCs, 13 HBCs, and 10 MESTs and assessed for nuclear
      immunohistochemical positivity in the tumor stroma. All cases of PMC and HBC
      demonstrated nuclear reactivity for FOXL2 in the subepithelial stromal cells.
      Ninety percent of MEST demonstrated nuclear FOXL2 positivity. Estrogen receptor
      nuclear positivity was demonstrated in 57% of PMC, 77% of HBC, and 80% of MEST.
      Progesterone receptor nuclear positivity was present in 67% of PMC, 100% of HBC,
      and 90% of MEST. Clinical information was available for 37 patients. Seventy
      eight percent of the patients had a history of obesity, heavy alcohol use, or
      hormone-related therapy. The 2 male patients had histories significant for morbid
      obesity and chronic alcoholism. FOXL2 is expressed from the early stages of
      ovarian development and has been shown to be mandatory for normal ovarian
      function. We have shown that it is also expressed in the aberrant ovarian-type
      stroma characteristic of PMC, HBC, and MEST. Most of such patients, including the
      rare male patients, have risk factors for hormonal abnormalities such as obesity
      and hormonal replacement therapy. 

PMID- 24746206
TI  - Aberrant expression of p53, p21, cyclin D1, and Bcl2 and their
      clinicopathological correlation in ampullary adenocarcinoma.
AB  - Previous studies on the molecular alterations in ampullary adenocarcinoma (AA)
      are limited, and little is known about their clinical implications. The objective
      of this study is to examine the expression of p53, p21, cyclin D1, and Bcl2 and
      their clinical significance in patients with AA. Tissue microarrays were
      constructed using archival tissue from 92 patients with AA who underwent
      pancreaticoduodenectomy at our institution. Each tumor was sampled in triplicate
      with a 1.0-mm punch from representative areas. The expression of p53, p21, cyclin
      D1, and Bcl2 was evaluated by immunohistochemistry, and the staining results were
      correlated with clinicopathological features and survival. Among 92 cases
      studied, overexpression of p53, p21, cyclin D1, and Bcl2 was observed in 58.7%,
      39.2%, 71.7%, and 5.4% of tumors, respectively. Patients whose tumor showed high
      level of cyclin D1 expression had higher risk of disease recurrence (P = .02) and
      worse recurrence-free and overall survivals after pancreaticoduodenectomy than
      did those with no or low cyclin D1 expression (P = .027 and P = .02,
      respectively). In multivariate analysis, cyclin D1 expression was an independent
      prognostic factor for both recurrence-free and overall survival (P < .05).
      However, there was no significant correlation between p53, p21, or Bcl2
      expression and survival (P > .05). Our study showed that p53, p21, and cyclin D1,
      but not Bcl2, are frequently overexpressed in AAs. Cyclin D1 overexpression is
      associated with increased risk of disease recurrence and worse survival in
      patients with AA after resection. 

PMID- 24746207
TI  - Use of CD137 ligand expression in the detection of small B-cell lymphomas
      involving the bone marrow.
AB  - Staging for small B-cell lymphomas is important for prognostic and therapeutic
      decision making; however, the detection of lymphoid infiltrates in the bone
      marrow is often hampered by the lack of specific diagnostic markers. We recently
      described the hematopoietic tissue distribution patterns of CD137 and CD137
      ligand (CD137L), which have shown promise as immunotherapeutic targets. CD137
      expression was primarily confined to cells in the microenvironment, whereas
      CD137L was expressed in neoplastic cells in most B-cell lymphomas. Here we
      evaluate the use of CD137L in the detection of small B-cell lymphomas involving
      the bone marrow. To test the potential efficacy of CD137L in detecting bone
      marrow lymphoid infiltrates, 166 small B-cell lymphomas were evaluated by
      immunohistochemistry and double-immunofluorescence labeling on formalin-fixed,
      paraffin-embedded bone marrow core biopsies. CD137L was highly expressed in bone
      marrows involved by small B-cell lymphomas and included hairy cell leukemia,
      mantle cell lymphoma, follicular lymphoma, B-lymphoblastic leukemia, and chronic
      lymphocytic leukemia. In addition, a small subset of marginal zone lymphoma and
      most of lymphoplasmacytic lymphoma showed staining. Normal bone marrow cells
      including myeloid, erythroid and megakaryocytic precursors, and reactive lymphoid
      aggregates lacked staining. Our findings show that immunohistochemistry for
      CD137L is capable of reliably distinguishing small B-cell lymphomas from reactive
      lymphoid aggregates. These data also suggest that CD137L is useful in providing
      staging information for clinical diagnosis and is likely to furnish a potential
      target for minimal residual disease assessment as well as immunotherapy in
      patients with stage 4 disease. 

PMID- 24746208
TI  - Cthrc1 overexpression is an independent prognostic marker in gastric cancer.
AB  - Collagen triple helix repeat containing 1 (CTHRC1) was identified as a novel gene
      expressed in the adventitia and neointima on arterial injury and was found to be
      overexpressed in several malignant tumors, such as breast cancer and malignant
      melanoma. However, the expression of Cthrc1 and its role in gastric cancer
      progression remain unknown. We investigated the expression of the Cthrc1 protein
      by immunohistochemistry in 30 normal tissues from the control subjects and 166
      gastric carcinomas and analyzed its correlation with various clinicopathological
      features, including patient outcome. Cthrc1 immunoreactivity was overexpressed in
      gastric carcinoma cases compared with normal tissues (P < .001). High Cthrc1
      expression was found in 108 (65.06%) of these 166 carcinomas and was positively
      correlated with the American Joint Committee on Cancer stage classification,
      depth of gastric wall invasion, lymph node metastasis, lymphovascular space
      involvement, and recurrence but not with age, tumor site, and carcinoembryonic
      antigen level. Patients with high Cthrc1 expression had significantly poorer
      overall survival and disease-free survival compared with patients with low
      expression of Cthrc1 (P = .001 and P = .002, respectively). Multivariate analysis
      showed that high Cthrc1 expression was an independent prognostic factor for both
      overall survival and disease-free survival of patients with gastric carcinoma
      (both P = .005). These results showed that high Cthrc1 expression was associated
      with progression and prognosis of gastric carcinoma. 

PMID- 24746209
TI  - Alveolar soft part sarcoma and granular cell tumor: an immunohistochemical
      comparison study.
AB  - Although the histologic features of alveolar soft part sarcoma and granular cell
      tumor are typically distinctive, occasional cases show a significant morphologic
      overlap. Differentiating these entities is crucial because granular cell tumor is
      almost always benign and alveolar soft part sarcoma is invariably malignant. We
      evaluated a panel of immunohistochemical stains (S-100 protein, inhibin, SOX10,
      nestin, calretinin, and TFE3) in 13 alveolar soft part sarcomas and 11 granular
      cell tumors. Tissue sections were also stained by the periodic acid-Schiff method
      after diastase digestion (PAS-D) and evaluated for coarse cytoplasmic granularity
      or crystalline cytoplasmic inclusions. S-100 protein, inhibin, SOX10, and nestin
      each distinguished granular cell tumor and alveolar soft part sarcoma with 100%
      sensitivity and specificity. PAS-D staining also distinguished cases with 100%
      accuracy, as granular cell tumor consistently demonstrated coarsely granular, PAS
      D-positive cytoplasm and alveolar soft part sarcoma showed only focal
      intracytoplasmic crystalline inclusions. Although all granular cell tumors were
      calretinin positive, so were 46% of alveolar soft part sarcomas. TFE3 was
      positive in 91% of granular cell tumors and all alveolar soft part sarcomas.
      Together with PAS-D, immunohistochemical stains for S-100 protein, inhibin,
      SOX10, and nestin accurately identify alveolar soft part sarcoma and granular
      cell tumor. Although TFE3 has been reported as a relatively specific marker for
      alveolar soft part sarcoma, it should be recalled that it is also expressed in
      most granular cell tumors. 

PMID- 24746210
TI  - A subset of small cell lung cancer with low neuroendocrine expression and good
      prognosis: a comparison study of surgical and inoperable cases with biopsy.
AB  - Patients with small cell lung carcinoma (SCLC) rarely demonstrate long-term
      survival. We previously reported that gene expression profiling identified a
      subset of SCLC with good prognosis in surgical cases. To find an easier way to
      routinely identify SCLC belonging to this subset, we conducted the present study
      with a hypothesis that neuroendocrine (NE) or basaloid (BA) phenotypes may
      influence prognosis. To confirm the subset, we used an array platform to analyze
      fresh samples. Because inoperable cases may differ from surgical cases, we
      enrolled 51 biopsy cases and 43 resected samples. To evaluate NE and BA
      phenotypes, we used NE (synaptophysin, chromogranin A, and CD56) and BA (p63 and
      CK34betaE12) markers. To varying extents, expression profiling based on the array
      platform duplicated the subsets. For NE phenotypes, 77% of surgical cases and
      100% of biopsy cases were positive for at least 1 marker. For BA phenotypes, only
      19% of surgical cases were positive for at least 1 marker, whereas there were no
      positive biopsy cases. Cases undergoing surgery were categorized based on NE and
      BA immunoreactivity; 58% into NE+BA-, 19% into NE+BA+, 23% into NE-BA-, and 0
      into NE-BA+ groups. NE- patients (n = 10) demonstrated a significantly better
      prognosis (P = .0306) than their NE+ counterparts (n = 33), whereas no survival
      difference was evident between the BA+ and BA- groups. Multivariate analyses
      showed that NE positivity was an independent prognostic factor. In conclusion,
      the SCLC subset with good prognosis is identified by low NE marker expression,
      which was found only in surgical cases. 

PMID- 24746211
TI  - The use of Yes-associated protein expression in the diagnosis of persistent
      neonatal cholestatic liver disease.
AB  - Although physiologic jaundice of neonates is common, persistent neonatal
      cholestasis is life-threatening and has multiple etiologies. Among these
      etiologies, biliary atresia (BA) requires rapid diagnosis and treatment. In
      diagnosing BA, the surgical pathologist must recognize subtle histologic changes,
      often with only a small core liver biopsy. To aid in the differential diagnosis
      of neonatal cholestasis, we investigated Yes-associated protein (YAP), a
      regulator of organ size and bile duct development. We examined whether a YAP
      immunostain can highlight emerging hepatobiliary epithelium in BA (n = 28) versus
      other causes of persistent cholestasis (non-BA; n = 15) and thus serve as a
      useful diagnostic marker in persistent neonatal jaundice. We show significantly
      (P < .01) more high-grade (<2) fibrosis and ductular proliferation among BA
      versus non-BA cases. Likewise, there was significantly more high-grade (2-3/3)
      cytoplasmic and nuclear YAP staining in BA (97% and 89%) versus non-BA (20% and
      13%). High-grade nuclear YAP staining was both sensitive (88%) and specific (87%)
      for the diagnosis of BA. In contrast to neonatal cholestasis, the differences in
      YAP localization in cholestatic/obstructed versus nonobstructed adult livers were
      not significant. Lastly, we found that pharmacologic inhibition of the YAP
      complex in both cholangiocyte and cholangiocarcinoma cell lines blocked
      compensatory bile duct proliferation, an early marker of BA that requires nuclear
      YAP expression, in a time- and dose-dependent manner. In summary, we show that
      YAP expression modulates both bile duct proliferation and liver damage/fibrosis
      while acting as a sensitive and specific marker in the differential diagnosis of
      persistent neonatal cholestasis. 

PMID- 24746212
TI  - Y-chromosome status identification suggests a recipient origin of posttransplant
      non-small cell lung carcinomas: chromogenic in situ hybridization analysis.
AB  - Owing to the need of lifelong immunosuppression, solid-organ transplant
      recipients are known to have an increased risk of posttransplant malignancies
      including lung cancer. Posttransplant neoplastic transformation of donor-derived
      cells giving rise to hematopoietic malignancies, Kaposi sarcoma, and basal cell
      carcinoma in nongraft tissues has been reported. The goal of this study was to
      assess the cell origin (donor versus recipient derived) of posttransplant non
      small cell lung carcinomas (NSCLCs) in kidney and heart transplant recipients. An
      institutional database search identified 2557 kidney and heart transplant
      recipients in 8 consecutive years. Among this cohort, 20 (0.8%) renal and 18
      (0.7%) heart transplant recipients developed NSCLC. The study cohort comprised 6
      of 38 NSCLCs arising in donor-recipient sex-mismatched transplant patients. The
      tumor cell origin was evaluated by chromogenic in situ hybridization with Y
      chromosome probe on formalin-fixed, paraffin-embedded tissues. Y-chromosome was
      identified in 97% +/- 1% (range from 92% to 99%) of all types of nucleated cells
      in male control tissues. In all 5 NSCLCs from male recipients of female donor
      organ, Y-chromosome was identified in 97% +/- 2% (range from 92% to 100%) of
      tumor cells, statistically equivalent to normal control (P < .001). No Y
      chromosome was identified in NSCLC cells from a female recipient of male kidney.
      These findings suggest a recipient derivation of NSCLC arising in kidney and
      heart transplant recipients. A combination of histologic evaluation and
      chromogenic in situ hybridization with Y-chromosome analysis allows reliable
      determination of tissue origin in sex-mismatched solid-organ transplant
      recipients and may aid in management of posttransplant malignancy in such cases. 

PMID- 24746213
TI  - Decreased mitochondrial SIRT3 expression is a potential molecular biomarker
      associated with poor outcome in breast cancer.
AB  - SIRT3 is a genomically expressed, mitochondrial localized tumor suppressor
      protein where it directs multiple metabolic processes by deacetylating downstream
      protein substrates. Genetic deletion of Sirt3 in mice leads to the spontaneous
      development of mammary tumors starting at 1 year, and decreased SIRT3 messenger
      RNA has been observed in several human tumors including breast malignancies. In
      this investigation, we assessed SIRT3 expression in human breast cancer tissue
      microarray and examined the relationship between SIRT3 expression and outcome in
      patients with breast cancer. SIRT3 protein expression is significantly lower in
      neoplastic compared with normal breast epithelium, including normal epithelium
      adjacent to tumors. Patients with breast cancer in the lowest quartile of SIRT3
      expression had a significantly shorter locoregional relapse-free survival (hazard
      ratio, 0.53 [0.47-0.61]; log-rank P = 0). Notably, low SIRT3 expression was
      associated with reduced locoregional relapse-free survival in all breast cancer
      subtypes analyzed, including ER+, ER-, HER2+, and basal subtypes (hazard ratios,
      0.44-0.65; log-rank P = 0-.0019). These results highlight the importance of the
      SIRT3 as a tumor suppressor protein in breast cancer and suggest that SIRT3 may
      be a potential molecular biomarker to identify high-risk patients across all
      molecular subtypes of breast cancer. 

PMID- 24746214
TI  - p40 exhibits better specificity than p63 in distinguishing primary skin adnexal
      carcinomas from cutaneous metastases.
AB  - The histopathologic distinction between primary adnexal carcinomas and metastatic
      adenocarcinoma to the skin from sites such as the breast, lung, and others often
      presents a diagnostic dilemma. Current markers of diagnostic utility include p63
      and cytokeratin 5/6; however, their expression has been demonstrated in 11% to
      22% and 27% of cutaneous metastases, respectively. Furthermore, the
      immunoreactivity of p40 and GATA3 in various cutaneous adnexal carcinomas has not
      been previously reported. In the present study, we compared the expression of
      p40, p63, cytokeratin 5/6, and GATA3 in a total of 143 cases, including 67
      primary adnexal carcinomas and 76 cutaneous metastases. p40, p63, cytokeratin
      5/6, and GATA3 expression was observed in 80%, 84%, 86%, and 47% of primary
      adnexal carcinoma, respectively, and in 8%, 17%, 26%, and 40% of cutaneous
      metastases, respectively. chi(2) Analysis revealed statistically significant P
      values (<.0001) for p40, p63, and cytokeratin 5/6 in distinguishing primary
      adnexal carcinoma from cutaneous metastases. In summary, while p63 and
      cytokeratin 5/6 have similar sensitivity (84% and 86%, respectively) in detecting
      primary adnexal carcinomas, p40 appeared to be the most specific marker (92%)
      with the best positive predictive value (90%). Since breast and lung are the most
      common sites of origin for cutaneous metastases, p40 is the best distinguishing
      marker in these settings. None of the four studied markers (p40, p63, cytokeratin
      5/6, and GATA3) are helpful in distinguishing between primary adnexal carcinomas
      from cutaneous metastases of salivary gland or bladder malignancies. 

PMID- 24746215
TI  - Extraskeletal myxoid chondrosarcoma with non-EWSR1-NR4A3 variant fusions
      correlate with rhabdoid phenotype and high-grade morphology.
AB  - Extraskeletal myxoid chondrosarcomas (EMC) are rare soft tissue sarcomas with
      distinctive histology and uncertain histogenesis, characterized by Ewing sarcoma
      breakpoint region 1-nuclear receptor subfamily 4, group A, member 3 (EWSR1-NR4A3)
      fusion in 75% of the cases. A smaller proportion of cases show NR4A3 fused to
      other gene partners including TATA binding protein-associated factor 15 (TAF15),
      transcription factor 12 (TCF12), and TRK-fused gene (TFG). The impact of various
      gene fusions on morphology and outcome has not been previously evaluated. We
      investigated 26 consecutive EMCs and correlated the genetic findings with
      morphology and clinical outcome. There were 5 females and 21 males (median age,
      49.5 years). Mean size of the tumors was 11 cm. Fluorescence in situ
      hybridization analysis showed EWSR1-NR4A3 gene fusion in 16 cases (62%), TAF15
      NR4A3 gene fusion in 7 cases (27%), and TCF12-NR4A3 gene fusion in 1 case (4%).
      Two cases showed only NR4A3 gene rearrangements. Morphologically, most EWSR1
      rearranged tumors (10/16) showed low cellularity, minimal cytologic atypia, and
      low mitotic counts. In contrast, 80% of EMCs with variant (non-EWSR1) NR4A3 gene
      fusions (TAF15, TCF12) had high-grade morphology with increased cellularity,
      proliferation, and cytologic atypia, showing a plasmacytoid/rhabdoid morphology
      in half the cases. Follow-up showed that only 1 of 16 patients with EWSR1
      rearranged tumors died of disease, in contrast to 3 (43%) of 7 TAF15-rearranged
      tumors. In conclusion, EMCs with variant NR4A3 gene fusions show a higher
      incidence of rhabdoid phenotype, high-grade morphology, and a more aggressive
      outcome compared with the EWSR1-NR4A3 positive tumors. Furthermore, fluorescence
      in situ hybridization assay for NR4A3, along with EWSR1, may be an additional
      ancillary test to confirm diagnosis of EMCs. 

PMID- 24746217
TI  - Benign perivascular myoid cell tumor (myopericytoma) of the urinary tract: a
      report of 2 cases with an emphasis on differential diagnosis.
AB  - Myopericytoma is a benign mesenchymal neoplasm thought to comprise part of a
      spectrum of perivascular myoid cell neoplasms with myofibroma, angioleiomyoma,
      and glomus tumor. We describe 2 such neoplasms involving the urinary tract: 1
      incidentally identified in the kidney of a 59-year-old woman and 1 in the urinary
      bladder of a 52-year-old woman who presented with urinary frequency and dysuria.
      Histologically, the bladder tumor was composed of numerous blood vessels
      surrounded by plump perivascular myoid cells, as in subcutaneous myopericytoma.
      The renal tumor showed similar morphology centrally and a symplastic glomus tumor
      like growth pattern at the periphery. Immunohistochemically, both tumors were
      reactive for markers of smooth muscle differentiation, such as smooth muscle
      actin and caldesmon/calponin but negative for CD34, cathepsin K, and S100
      protein. Both patients are free of disease 14 and 39 months after resection,
      respectively. Our findings broaden the morphologic spectrum of myopericytoma. 

PMID- 24746223
TI  - The cost of premature cancer-related mortality: a review and assessment of the
      evidence.
AB  - Worldwide, 8.2 million people die of cancer annually. Cancer has a significant
      societal impact, impinging on countries' economic health. We reviewed
      methodological aspects, and the main cost results, of studies calculating
      premature mortality losses from cancer published 2000-2013 and identified gaps in
      the evidence-base. Thirty-one studies were identified (Europe, 17; USA, 11;
      Korea, 2; Puerto Rico, (1). The human capital approach dominated (30 studies);
      studies differed in how they implemented the methodological approach. Aspects of
      methodology were poorly reported. Premature cancer-related mortality costs are
      substantial and appear to be rising. The evidence-base has gaps in relation to
      cancer sites studied and less developed and emerging economies. Comprehensive,
      standardised, estimates of premature mortality losses are needed if these
      measures are to be useful in assessing the societal cancer burden. 

PMID- 24746216
TI  - Analysis and validation of tissue biomarkers for renal cell carcinoma using
      automated high-throughput evaluation of protein expression.
AB  - The objective of this study was to compare the predictive ability of potential
      tissue biomarkers to known prognostic factors that predict renal cell carcinoma
      (RCC) recurrence using an automated system of immunohistochemical analysis. After
      institutional review board approval, a tissue microarray was constructed using
      tissue from patients who had partial or radical nephrectomy for RCC. Patients
      with metastatic disease were excluded. Immunohistochemical staining of the tissue
      microarray for Ki-67, C-reactive protein, carbonic anhydrase 9, and hypoxia
      inducible factors 1alpha and 2alpha was analyzed using automated image analysis.
      Univariable and multivariable analyses were performed to evaluate the association
      of putative biomarkers and known prognostic factors. Of 216 patients who met the
      entrance criteria, 34 (16%) patients developed metastatic recurrence within a
      median follow-up interval of 60.9 (interquartile range, 13.9-87.1) months. RCC
      morphotypes analyzed in this study include clear cell (n = 156), papillary (n =
      38), chromophobe (n = 16), and collecting duct/unclassified (n = 6). Univariate
      analysis identified that only increased Ki-67 was predictive of RCC recurrence
      among the proteins evaluated, in addition to other known clinicopathological
      prognostic factors. After multivariate analysis, Ki-67 was identified as an
      independently predictive risk factor for RCC recurrence (hazard ratio [HR], 3.73
      [confidence interval {CI}, 1.60-8.68]). Other independent predictors of RCC
      recurrence included tumor diameter (HR, 1.20 [CI, 1.02-1.41]) and perinephric fat
      invasion (HR, 4.49 [CI, 1.11-18.20]). We conclude that Ki-67 positivity is
      independently predictive of RCC recurrence after surgery in nonmetastatic
      patients. Automated analysis of tissue protein expression can facilitate a more
      objective and expedient investigation of tissue biomarkers for RCC. 

PMID- 24746224
TI  - Bee venom acupuncture, NSAIDs or combined treatment for chronic neck pain: study
      protocol for a randomized, assessor-blind trial.
AB  - BACKGROUND: Chronic neck pain (CNP) is a common painful medical condition with a
      significant socioeconomic impact. In spite of widespread usage, the effectiveness
      and safety of combined treatments between conventional and complementary
      alternative medical treatment modalities has not been fully established in a
      rigorous randomized clinical trial (RCT). This pilot study will provide the
      clinical evidence to evaluate the feasibility and refine the protocol for a full
      scale RCT on combined treatment of bee venom acupuncture (BVA) and non-steroidal
      anti-inflammatory drugs (NSAIDs) in patients with CNP. METHODS/DESIGN: This is a
      randomized, single-blind clinical trial with three parallel arms. Sixty patients
      between 18 and 65 years of age with non-specific, uncomplicated neck pain lasting
      for at least three months will be enrolled. Participants will be randomly
      allocated into the BVA, NSAIDs or combined treatment group. Assessors and
      statisticians will be blinded to the random allocation. All researchers will
      receive training to ensure their strict adherence to the study protocol. Patients
      from the BVA and combined treatment group will be treated with a bee venom
      increment protocol into predefined acupoints for six sessions over a three week
      period. BVA intervention is developed through a comprehensive discussion among
      interdisciplinary spine disorder experts, according to the guidelines of
      Standards for Reporting Interventions in Clinical Trials of Acupuncture
      (STRICTA). Patients from the NSAIDs and combined treatment groups will be
      prescribed loxoprofen (one tablet to be taken orally, three times a day for three
      weeks). Bothersomeness from CNP measured using a visual analogue scale (VAS) will
      be the primary outcome assessed at screening, visit two (baseline), four, six,
      eight (4th week assessment) and nine (8th week assessment) follow-up session. VAS
      for pain intensity, neck disability index (NDI), quality of life, depressive
      status and adverse experiences will also be analyzed. DISCUSSION: Our study
      results will contribute to feasibility evaluation and to relevant RCT protocol
      development for a full-scale RCT on combined treatment of BVA and NSAIDs for CNP
      patients. TRIAL REGISTRATION: This study is registered with the United States
      (US) National Institutes of Health Clinical Trials Registry: NCT01922466.

PMID- 24746225
TI  - 2,4-Bis(4-hydroxybenzyl)phenol inhibits heat shock transcription factor 1 and
      sensitizes lung cancer cells to conventional anticancer modalities.
AB  - Heat shock factor 1 (HSF1) is a transcription factor that regulates expression of
      heat shock protein (HSP) genes in response to stress. HSPs are expressed at high
      levels in a wide range of tumors. It has been reported that HSF1 and HSPs are
      associated closely in tumorigenesis. In the present study, a screen was performed
      using a luciferase reporter under the control of a heat shock element to find
      inhibitors of HSF1 activity, and 2,4-bis(4-hydroxybenzyl)phenol (1), isolated
      from the rhizomes of Gastrodia elata, was identified as an active compound. This
      substance effectively inhibited HSF1 activity and decreased levels of HSP27 and
      HSP70. Compound 1 induced the degradation of HSF1 protein through
      dephosphorylation of HSF1 on S326, which decreases HSF1 protein stability. In
      addition, 1 also induced growth arrest and apoptosis of NCI-H460 human lung
      cancer cells. Markers of apoptosis, such as cleaved PARP and cleaved caspase-3,
      were detected after treatment with 1. Furthermore, cotreatment with 1 and
      conventional anticancer modalities such as paclitaxel, cisplatin, or ionizing
      radiation potentiated their effects on lung cancer cells. These results suggest
      that inhibition of HSF1 by 1 may help overcome resistance to conventional
      anticancer modalities in HSF1-overexpressed cancer cells. 

PMID- 24746226
TI  - Lead halide perovskites and other metal halide complexes as inorganic capping
      ligands for colloidal nanocrystals.
AB  - Lead halide perovskites (CH3NH3PbX3, where X = I, Br) and other metal halide
      complexes (MX(n), where M = Pb, Cd, In, Zn, Fe, Bi, Sb) have been studied as
      inorganic capping ligands for colloidal nanocrystals. We present the methodology
      for the surface functionalization via ligand-exchange reactions and the effect on
      the optical properties of IV-VI, II-VI, and III-V semiconductor nanocrystals. In
      particular, we show that the Lewis acid-base properties of the solvents, in
      addition to the solvent dielectric constant, must be properly adjusted for
      successful ligand exchange and colloidal stability. High luminescence quantum
      efficiencies of 20-30% for near-infrared emitting CH3NH3PbI3-functionalized PbS
      nanocrystals and 50-65% for red-emitting CH3NH3CdBr3- and (NH4)2ZnCl4-capped
      CdSe/CdS nanocrystals point to highly efficient electronic passivation of the
      nanocrystal surface.

PMID- 24746227
TI  - A fullerene-based multi-functional nanoplatform for cancer theranostic
      applications.
AB  - Recently, nanomaterials with multiple functions, such as drug carrier, MRI and
      optical imaging, photothermal therapy etc, have become more and more popular in
      the domain of cancer research. In this study, a C60-IONP nanocomposite is
      synthesized via decorating iron oxide nanoparticles (IONP) onto fullerene (C60)
      and then functionalized by polyethylene glycol (PEG2000), giving C60-IONP-PEG
      with excellent stability in physiological solutions, finally folic acid (FA), a
      widely used tumor targeting molecule, was linked to C60-IONP-PEG in order to
      obtain an active tumor targeting effect to MCF-7 cells and malignant tumor in
      mice models. Herein, a hybrid nanoplatform with multi-functional characteristics
      for cancer diagnosis, photodynamic therapy (PDT), radiofrequency (RF) thermal
      therapy (RTT) and magnetic targeting applications was developed and explored its
      biofunctions in vitro and in vivo. C60-IONP-PEG-FA showed neglectable toxicity,
      not only served as a powerful tumor diagnostic magnetic resonance imaging (MRI)
      contrast agent, but also as a strong photosensitizer and powerful agent for
      photothermal ablation of tumor, furthermore a remarkable synergistic enhancement
      of PDT combination with RTT was also observed during the treatment both in vitro
      and in vivo. Moreover, the multi-functional nanoplatform also could selectively
      kill cancer cells in highly localized regions via the excellent active tumor
      targeting and magnetic targeted abilities. This work showed the multi-functional
      C60-IONP-PEG-FA nanoplatform had a great potential for cancer theranostic
      applications. 

PMID- 24746229
TI  - A continuous tri-phase transition effect for HIFU-mediated intravenous drug
      delivery.
AB  - Aiming at substantially enhanced efficacy and biosafety of clinical HIFU therapy,
      a natural solid medium, L-menthol (LM), characteristic of mild and controllable
      "solid-liquid-gas" (SLG) tri-phase transition, was adopted, instead of those
      conventional explosive liquid-gas (LG) bi-phase transitional media, in
      constructing a multifunctional theranostic system. Owing to the continuous and
      controllable characteristics of SLG tri-phase transition, such a novel tri-phase
      transition-based theranostic system has been demonstrated of the repeatedly
      enhanced HIFU efficacy ex vivo and in vivo under once intravenous injection and
      the significantly improved treatment precision, controllability and biosafety
      when comparing to the traditional bi-phase transition medium, perfluorohexane
      (PFH), thus promising great application potential in clinical HIFU treatment.
      Moreover, this theranostic system has been demonstrated a long blood-circulation
      lifetime and continuous accumulation in tumor in 24 h, which is very beneficial
      for the enhanced tumor ablation in vivo along with SLG tri-phase transition. More
      importantly, after loading multiple model drugs and real drug, such a theranostic
      system presents a HIFU-mediated temperature-responsive drug release property, and
      depending on the versatile miscibility of LM, co-loadings with hydrophobic and
      hydrophilic drugs are also achieved, which provides the possibility of
      synergistic treatment combining HIFU therapy and chemotherapy. 

PMID- 24746228
TI  - Molecular factors in dendritic cell responses to adsorbed glycoconjugates.
AB  - Carbohydrates and glycoconjugates have been shown to exert pro-inflammatory
      effects on the dendritic cells (DCs), supporting pathogen-induced innate immunity
      and antigen processing, as well as immunosuppressive effects in the tolerance to
      self-proteins. Additionally, the innate inflammatory response to implanted
      biomaterials has been hypothesized to be mediated by inflammatory cells
      interacting with adsorbed proteins, many of which are glycosylated. However, the
      molecular factors relevant for surface displayed glycoconjugate modulation of
      dendritic cell (DC) phenotype are unknown. Thus, in this study, a model system
      was developed to establish the role of glycan composition, density, and carrier
      cationization state on DC response. Thiol modified glycans were covalently bound
      to a model protein carrier, maleimide functionalized bovine serum albumin (BSA),
      and the number of glycans per BSA modulated. Additionally, the carrier
      isoelectric point was scaled from a pI of ~4.0 to ~10.0 using ethylenediamine
      (EDA). The DC response to the neoglycoconjugates adsorbed to wells of a 384-well
      plate was determined via a high throughput assay. The underlying trends in DC
      phenotype in relation to conjugate properties were elucidated via multivariate
      general linear models. It was found that glycoconjugates with more than 20
      glycans per carrier had the greatest impact on the pro-inflammatory response from
      DCs, followed by conjugates having an isoelectric point above 9.5. Surfaces
      displaying terminal alpha1-2 linked mannose structures were able to increase the
      inflammatory DC response to a greater extent than did any other terminal glycan
      structure. The results herein can be applied to inform the design of the next
      generation of combination products and biomaterials for use in future vaccines
      and implanted materials. 

PMID- 24746230
TI  - Effectiveness of deep cleaning followed by hydrogen peroxide decontamination
      during high Clostridium difficile infection incidence.
AB  - BACKGROUND: Clostridium difficile infection (CDI) remains an infection control
      challenge, especially when environmental spore contamination and suboptimal
      cleaning may increase transmission risk. AIM: To substantiate the long-term
      effectiveness throughout a stroke rehabilitation unit (SRU) of deep cleaning and
      hydrogen peroxide decontamination (HPD), following a high incidence of CDI.
      METHODS: Extensive environmental sampling (342 sites on each occasion) for C.
      difficile using sponge wipes was performed: before and after deep cleaning with
      detergent/chlorine agent; immediately following HPD; and on two further
      occasions, 19 days and 20 weeks following HPD. C. difficile isolates underwent
      polymerase chain reaction ribotyping and multi-locus variable repeat analysis
      (MLVA). FINDINGS: C. difficile was recovered from 10.8%, 6.1%, 0.9%, 0% and 3.5%
      of sites at baseline, following deep cleaning, immediately after HPD, and 19 days
      and 20 weeks after HPD, respectively. C. difficile ribotypes recovered after deep
      cleaning matched those from CDI cases in the SRU during the previous 10 months.
      Similarly, 10/12 of the positive sites identified at 20 weeks post-HPD harboured
      the same C. difficile ribotype (002) and MLVA pattern as the isolate from the
      first post-HPD CDI case. CDI incidence [number of cases on SRU per 10 months
      (January-October 2011)] declined from 20 before to seven after the intervention.
      CONCLUSION: HPD, after deep cleaning with a detergent/chlorine agent, was highly
      effective for removing environmental C. difficile contamination. Long-term follow
      up demonstrated that a CDI symptomatic patient can rapidly recontaminate the
      immediate environment. Determining a role for HPD should include long-term cost
      effectiveness evaluations.

PMID- 24746231
TI  - Disinfecting the iPad: evaluating effective methods.
AB  - BACKGROUND: Tablet computers are increasingly used in healthcare, but they may
      carry nosocomial pathogens. There are few data available on how to clean an iPad
      effectively for use in the clinical setting. AIM: We aimed to identify the most
      effective method of decontaminating the Apple iPad, without causing damage, and
      establish the duration of any residual effect. METHODS: Following contamination
      with a microbial broth (meticillin-resistant Staphylococcus aureus (MRSA),
      vancomycin-resistant enterococcus (VRE) and Clostridium difficile), we examined
      efficacy of iPad disinfection in the laboratory using six different disinfectant
      wipes: Sani-Cloth CHG 2% (chlorhexidine 2%/alcohol 70%), Clorox, Tristel,
      Trigene, soap and water, and plain cloth. Following cleaning, iPads were
      recontaminated to examine residual activity. After 480 Sani-Cloth CHG 2%
      disinfecting episodes, functional and visual analysis of iPads was performed by
      blinded subjects. FINDINGS: With the exception of Clostridium difficile, Sani
      Cloth CHG 2% and Clorox wipes were most effective against MRSA and VRE, and they
      were significantly better than the Apple-recommended plain cloth (P <= 0.001). A
      substantial residual antimicrobial effect was seen for >6h after wiping the iPad
      with Sani-Cloth CHG 2% despite repeated recontamination and without further
      disinfection. The functionality or visual appearance of the iPad was not damaged
      by repeated use of Sani-Cloth CHG 2% wipes. CONCLUSIONS: Sani-Cloth CHG 2% wipes
      effectively disinfect the iPad against MRSA and VRE, with a residual
      antibacterial effect and without causing damage.

PMID- 24746232
TI  - Surveillance and molecular characterization of non-tuberculous mycobacteria in a
      hospital water distribution system over a three-year period.
AB  - A three-year surveillance of non-tuberculous mycobacteria (NTM) in a hospital
      water distribution system was conducted at a facility located in southern
      Alberta. NTM was not present in any intake water samples, but was found in
      106/183 (58%) of endpoint samples across 15 sites over the study period. Two
      different species of NTM were identified, Mycobacterium gordonae (88/183) and
      Mycobacterium avium (34/183); with only one strain of each M. gordonae and M.
      avium found. Given the sensitive nature of a healthcare facility, attention
      should be paid to minimize potential impact of NTM from potable water sources on
      patient health.

PMID- 24746233
TI  - The pharmacokinetic considerations and adverse effects of DPP-4 inhibitors
      [corrected].
AB  - INTRODUCTION: Dipeptidyl-peptidase-4 (DPP-4) inhibitors are a class of anti
      hyperglycemic agents with proven efficacy in patients with type 2 diabetes
      mellitus (T2DM). AREAS COVERED: This review considers the pharmacokinetic
      profile, adverse effects and drug interactions of DPP-4 inhibitors. DPP-4
      inhibitors have certain differences in their structure, metabolism, route of
      elimination and selectivity for DPP-4 over structurally related enzymes, such as
      DPP-8/DPP-9. They have a low potential for drug interactions, with the exception
      of saxagliptin that is largely metabolized by cytochrome CYP3A4/A5. Reports of
      pancreatitis and pancreatic cancer have raised concerns regarding the safety of
      DPP-4 inhibitors and are under investigation. Post-marketing surveillance has
      revealed less common adverse effects, especially a number of skin- and immune
      related adverse effects. These issues are covered in the present review. EXPERT
      OPINION: DPP-4 inhibitors are useful and efficient drugs. DPP-4 inhibitors have
      similar mechanism of action and similar efficacy. However, DPP-4 inhibitors have
      certain differences in their pharmacokinetic properties that may be associated
      with different clinical effects and adverse event profiles. Although clinical
      trials indicated a favorable safety profile, post-marketing reports revealed
      certain safety aspects that need further investigation. Certainly, more research
      is needed to clarify if the differences among DPP-4 inhibitors could lead to a
      different clinical and safety profile.

PMID- 24746235
TI  - Prevalence and genotype of Toxoplasma gondii infection in cattle from Jilin
      Province, northeastern China.
AB  - Abstract The prevalence and genotype of Toxoplasma gondii infection in cattle in
      Jilin Province, northeastern China was investigated. A total of 1040 serum
      samples were collected from eight administrative regions from September to
      October, 2011, and antibodies to T. gondii were examined by enzyme-linked
      immunosorbent assay (ELISA). The results showed that the overall seroprevalence
      of T. gondii in cattle was 12.8% (95% confidence interval [CI], 10.8-14.8%), with
      a higher prevalence of 22.2% (95% CI 13.6-30.8%) in Siping. Sixty-six tissue
      samples were collected from Changchun, and T. gondii DNA was detected by a nested
      PCR. There were nine (13.6%; 95% CI 5.4-21.9%) positive samples, which were
      genotyped using 11 genetic markers for PCR restriction fragment length
      polymorphisms (RFLP). Only one sample could be completely genotyped, and all of
      the loci were grouped into clonal type I, except for type III at the GRA6 locus,
      implying that T. gondii in cattle in Changchun, Jilin Province was type I
      variant. This study is the first report on genotype of T. gondii infection in
      cattle in China. 

PMID- 24746236
TI  - Distribution and characterization of Heterobilharzia americana in dogs in Texas.
AB  - Heterobilharzia americana is a trematode parasite (family Schistosomatidae) that
      infects a wide range of wild mammalian hosts. Canine cases have been reported in
      the Gulf coast and south Atlantic states, Kansas, and Oklahoma. A total of 238
      canine H. americana cases in Texas were retrospectively collected for a period of
      approximately 22 years from case records at the Texas Veterinary Medical
      Diagnostic Laboratory and the Veterinary Medical Teaching Hospital pathology
      service, diagnostic parasitology service, and Gastrointestinal Laboratory at
      Texas A&M University College of Veterinary Medicine. Of these cases, 26 patients
      had 1-2 repeat positive tests for a total of 268 positive tests (26 biopsies, 39
      necropsies, 160 fecal examinations, and 43 PCR). Multiple dogs were infected in
      12 households. Cases were distributed primarily in the eastern region of Texas in
      42 of 254 counties. Cases were seen as far west as Kerr county and in counties
      bordering Oklahoma, Louisiana, Mexico, and the Gulf of Mexico. The median dog age
      was 5.6 years (2.7 months to 17.2 years) and the median weight was 20.5 kg (1
      61.6 kg). All American Kennel Club (AKC) breed groups were represented (n=186):
      crossbred (20%), herding (17.8%), sporting (16.1%), toy (10.8%), hounds (10.8%),
      working (10.1%), terrier (8.5%), non-sporting (4.9%), and miscellaneous (1%). No
      seasonal pattern of diagnosis was apparent. Clinical signs reported (n=90) were
      diarrhea (67%), weight loss (38%), anorexia/hyporexia (27%), vomiting (22%),
      hematochezia (20%), lethargy (17%), polyuria/polydipsia (6%), and collapse (3%).
      In 39 necropsy cases, trematode eggs were identified by histopathology in the
      small intestine (84%), liver (84%), large intestine (39%), pancreas (35%), lung
      (9%), lymph node (8%), spleen (4%), and stomach (3%). Adult parasites were
      identified histologically in four cases. Granulomatous inflammation associated
      with the eggs was the most commonly reported histopathologic change. Other
      changes reported were fibrosis, pigment in macrophages, and organ mineralization.
      Glomerulonephritis was identified in four cases. Of 20 necropsy cases where death
      was attributable to H. americana infection, only one case was diagnosed ante
      mortem. Eleven of these dogs were examined by a veterinarian but H. americana was
      included as a differential diagnosis in only two cases. Reported differential
      diagnoses included ethylene glycol toxicity, cholecalciferol toxicity, lymphoma,
      and pancreatitis. These data indicate that this parasite is more widely
      distributed and more common than is generally recognized. Increased awareness may
      aid in more diagnoses and timely therapy.

PMID- 24746234
TI  - Genome sequence and transcriptome analyses of the thermophilic zygomycete fungus
      Rhizomucor miehei.
AB  - BACKGROUND: The zygomycete fungi like Rhizomucor miehei have been extensively
      exploited for the production of various enzymes. As a thermophilic fungus, R.
      miehei is capable of growing at temperatures that approach the upper limits for
      all eukaryotes. To date, over hundreds of fungal genomes are publicly available.
      However, Zygomycetes have been rarely investigated both genetically and
      genomically. RESULTS: Here, we report the genome of R. miehei CAU432 to explore
      the thermostable enzymatic repertoire of this fungus. The assembled genome size
      is 27.6-million-base (Mb) with 10,345 predicted protein-coding genes. Even being
      thermophilic, the G + C contents of fungal whole genome (43.8%) and coding genes
      (47.4%) are less than 50%. Phylogenetically, R. miehei is more closerly related
      to Phycomyces blakesleeanus than to Mucor circinelloides and Rhizopus oryzae. The
      genome of R. miehei harbors a large number of genes encoding secreted proteases,
      which is consistent with the characteristics of R. miehei being a rich producer
      of proteases. The transcriptome profile of R. miehei showed that the genes
      responsible for degrading starch, glucan, protein and lipid were highly
      expressed. CONCLUSIONS: The genome information of R. miehei will facilitate
      future studies to better understand the mechanisms of fungal thermophilic
      adaptation and the exploring of the potential of R. miehei in industrial-scale
      production of thermostable enzymes. Based on the existence of a large repertoire
      of amylolytic, proteolytic and lipolytic genes in the genome, R. miehei has
      potential in the production of a variety of such enzymes.

PMID- 24746237
TI  - High excretion of Cryptosporidium ubiquitum by peri-parturient goats in one flock
      in western France.
AB  - Cryptosporidium spp. is an important agent of neonatal diarrhoea in goat kids.
      Little is known about its molecular characterization in adult goats. A
      longitudinal study was set up to identify the species excreted by adult goats
      around parturition. Individual faecal samples were collected from 20 pregnant
      adult goats between 1 and 5 years old in one flock. Samplings began 3 weeks
      before the estimated kidding date and were done weekly until kidding and for 2
      weeks after kidding. Cryptosporidium oocysts were concentrated from 15 g of
      faeces using a caesium chloride (CsCl) method. Oocyst output was determined using
      a direct immunofluorescent antibody test (IFAT). Genomic DNA was extracted from
      each CsCl-concentrated faecal sample positive by IFAT and submitted to a nested
      PCR-RFLP on the SSU rDNA gene followed by sequencing to identify the isolates at
      species level. According to their kidding date, goats were sampled between 4 and
      8 times. Sixteen goats, out of the eighteen which kidded, were found positive at
      least at one sampling date. Infection was asymptomatic. Prevalence of excretion
      was maximal 14 days before kidding with half of the goats excreting oocysts at
      this date. Excretion was higher before kidding than after kidding. Unexpected
      levels of excretion were observed with individual oocyst excretion ranging from 6
      to 2.5 * 10(5) oocysts per gram of faeces. All isolates were identified as
      Cryptosporidium ubiquitum.

PMID- 24746238
TI  - Risk of infection by the consumption of liver of chickens inoculated with low
      doses of Toxocara canis eggs.
AB  - Experimental studies and registries of cases of human toxocariasis have shown
      that the consumption of raw or undercooked offal of the paratenic host of
      Toxocara canis may pose a risk of infection. Thus, we evaluated the risk of
      infection due to the consumption of liver of chickens inoculated with different
      doses of embryonated T. canis eggs. Doses were 5-100 times smaller than the ones
      previously employed in this type of study. Groups of five chickens were
      inoculated with 5000 (control), 1000, 500, 300 or 50 eggs of T. canis, and at 72
      h post-inoculation, the liver of each bird was consumed by a BALB/c receptor
      mouse. Forty-eight hours after consumption, we examined the organs and carcasses
      of the mice for larvae of T. canis. All mice were positive for larvae, except the
      group that consumed the chicken liver inoculated with 50 eggs. This group
      contained only one positive mouse, in which the larva was lodged in the brain. In
      mice that consumed livers of chickens inoculated with >=300 eggs, larvae
      concentration was primarily in the liver and lungs, characterizing the initial
      phase of infection. We conclude that the consumption of raw poultry liver, under
      the studied conditions, poses a risk of infection even with a low number of
      infected T. canis eggs.

PMID- 24746239
TI  - Mechanistic evaluation of motion in redox-driven rotaxanes reveals longer linkers
      hasten forward escapes and hinder backward translations.
AB  - Mechanistic understanding of the translational movements in molecular switches is
      essential for designing machine-like prototypes capable of following set pathways
      of motion. To this end, we demonstrated that increasing the station-to-station
      distance will speed up the linear movements forward and slow down the movements
      backward in a homologous series of bistable rotaxanes. Four redox-active
      rotaxanes, which drove a cyclobis(paraquat-p-phenylene) (CBPQT(4+)) mobile ring
      between a tetrathiafulvalene (TTF) station and an oxyphenylene station, were
      synthesized with only variations to the lengths of the glycol linker connecting
      the two stations (n = 5, 8, 11, and 23 atoms). We undertook the first mechanistic
      study of the full cycle of motion in this class of molecular switch using cyclic
      voltammetry. The kinetics parameters (k, DeltaG(?)) of switching were determined
      at different temperatures to provide activation enthalpies (DeltaH(?)) and
      entropies (DeltaS(?)). Longer glycol linkers led to modest increases in the
      forward escape (t(1/2) = 60 to <7 ms). The rate-limiting step involves movement
      of the tetracationic CBPQT(4+) ring away from the singly oxidized TTF(+) unit by
      overcoming one of the thiomethyl (SMe) speed bumps before proceeding on to the
      secondary oxyphenylene station. Upon reduction, however, the return translational
      movement of the CBPQT(4+) ring from the oxyphenylene station back to the neutral
      TTF station was slowed considerably by the longer linkers (t(1/2) = 1.4 to >69
      s); though not because of a diffusive walk. The reduced rate of motion backward
      depended on folded structures that were only present with longer linkers.

PMID- 24746240
TI  - Iodine nutrition in pregnant women from Oviedo area. Is iodine supplementation
      necessary?
AB  - BACKGROUND AND OBJECTIVE: In Asturias, where iodine deficiency was eradicated in
      school children by the year 2000, iodine deficiency persisted in pregnant women,
      who were recommended to use of iodine supplementation. The aim of this study was
      to determine the iodine nutrition of pregnant women in our area and whether or
      not iodine supplements are needed. MATERIAL AND METHODS: Throughout May and June
      2013 we studied the iodine nutrition and thyroid function during the first
      trimester of pregnancy in 173 women in the health area of Oviedo. RESULTS: The
      median urinary iodine was 197 MUg/L. Iodinated supplements were used by 47% of
      women, which had a yoduria median higher than those not taking iodinated
      supplements (247 vs. 138 MUg/L; p<.001), and also a higher TSH (2.30 vs 1.94
      mU/L) although not significantly different. Yoduria was also higher in women who
      took more than 2 servings of dairy products (median: 230 MUg/L) than those who
      took less (median: 191 MUg/L). Within the group of women who were not taking
      iodine supplements, those regularly using iodized salt in the kitchen (47%) had a
      median urinary iodine concentration of 190MUg/L indicating iodine sufficiency.
      CONCLUSIONS: Iodinated supplements seem unnecessary nowadays in pregnant women of
      Oviedo who regularly take iodized salt and our recommendation in these cases
      should be to continue the use of iodized salt in the recommended amounts during
      pregnancy and consume at least two daily servings of milk or dairy products.

PMID- 24746241
TI  - Beyond benzoin condensation: trimerization of aldehydes via metal-free aerobic
      oxidative esterification of aldehydes with benzoin products in the presence of
      cyanide.
AB  - An unusual trimerization of aldehydes in the presence of cyanide via metal-free
      aerobic oxidative esterification under ambient conditions is described. Various
      aromatic aldehydes provided the corresponding oxidative esterification products
      in good to excellent yields. Mechanistic studies suggested that this reaction
      would proceed via a two-step sequence: cyanide-catalyzed benzoin condensation of
      aldehydes and subsequent aerobic oxidative esterification of aldehydes with the
      resultant benzoin products. The usefulness of this protocol was further
      demonstrated by converting the resulting trimeric products into other
      biologically important compounds. 

PMID- 24746242
TI  - Interview with Malcolm J. Bennett.

PMID- 24746243
TI  - How is inflammation initiated? Individual influences of IL-1, IL-18 and HMGB1.
AB  - Pro-inflammatory cytokines are crucial for fighting infection and establishing
      immunity. Recently, other proteins, such as danger-associated molecular patterns
      (DAMPs), have also been appreciated for their role in inflammation and immunity.
      Following the formation and activation of multiprotein complexes, termed
      inflammasomes, two cytokines, IL-1beta and IL-18, along with the DAMP High
      Mobility Group Box 1 (HMGB1), are released from cells. Although these proteins
      all lack classical secretion signals and are released by inflammasome activation,
      they each lead to different downstream consequences. This review examines how
      various inflammasomes promote the release of IL-1beta, IL-18 and HMGB1 to combat
      pathogenic situations. Each of these effector molecules plays distinct roles
      during sterile inflammation, responding to viral, bacterial and parasite
      infection, and tailoring the innate immune response to specific threats. 

PMID- 24746244
TI  - High multi-cytokine levels are not a predictive marker of alloimmunization in
      transfused sickle cell disease patients.
AB  - Patients with sickle cell disease (SCD) receive multiple red blood cell (RBC)
      transfusions for both prevention of and therapy for disease-related
      complications. In some patients, transfusion results in development of both allo-
      and auto-antibodies to RBC antigens. What precipitates the antibody formation is
      currently unclear. It has been hypothesized that a pro-inflammatory state
      preceding the therapeutic transfusion may be a predisposing factor. Plasma levels
      of ten cytokines were evaluated upon recruitment to the study of 83 children with
      SCD undergoing therapeutic RBC transfusions. The levels of cytokines were
      correlated with development of anti-RBC antibodies prior, or during seven years
      post recruitment. Twelve subjects displayed significantly higher levels of all
      cytokines examined, with pro-, as well as anti-inflammatory properties.
      Surprisingly, the elevated levels of cytokines were preferentially found in
      patients without anti-RBC allo- and/or auto-antibodies. Further, presence of high
      cytokine levels was not predictive of anti-RBC antibody development during the
      subsequent seven year follow up. These data suggest that the increased
      concentration of multiple cytokines is not a biomarker of either the presence of
      or susceptibility to the development of RBC alloimmunization. 

PMID- 24746246
TI  - Experiences of well-being among female doctoral students in Sweden.
AB  - The aim of this study was to explore how female PhD students experience and
      perceive their well-being. Focus groups were conducted with female PhD students
      employed at a Swedish university. The study was performed using a
      phenomenological hermeneutic approach based on the concept of the lifeworld, used
      as both a philosophical perspective and a methodology. Three main themes emerged
      from the analysis: being true to oneself, being in the sphere of influence, and
      performing a balancing act. By unfolding these themes, the study shows that
      perceptions and experiences of well-being in female PhD students are a
      multifaceted phenomenon and materialize through interaction of different aspects
      of "self" (agent) and "others" (structure). As well as illustrating these
      perceptions and experiences, the study also presents female PhD students'
      conceptualization of their well-being, expressed in terms of a white-water
      rafting metaphor. 

PMID- 24746245
TI  - Young adults' use of food as a self-therapeutic intervention.
AB  - The aim of this study was to investigate how young adults use their lived body as
      a starting point for lifestyle explorations and as a strategy for well-being. The
      transcripts of 10 interviews with persons 18 to 33 years old, collected in
      Sweden, were analysed for variation in the practises and experiences related to
      this way of using food. An application of the descriptive phenomenological
      psychological research method guided the process. The young adults were: (1)
      listening to the body; (2) moderating conditions and feelings; (3) developing
      vitality and resilience; (4) creating mindful space for rest, and (5)
      participating in creative activity. The results show how young adults perceive
      their choice of food and related practises associated with positive feelings and
      experiences as ways to promote well-being and mitigate different problems in
      life. The usefulness of knowledge about how young adults try to use food for self
      therapy by enhancing mind-body awareness is discussed in relation to health
      issues and food-related interventions. 

PMID- 24746247
TI  - Skype interviewing: the new generation of online synchronous interview in
      qualitative research.
AB  - The most commonly used method for data collection in qualitative research is
      interviewing. With technology changes over the last few decades, the online
      interview has overcome time and financial constraints, geographical dispersion,
      and physical mobility boundaries, which have adversely affected onsite
      interviews. Skype as a synchronous online service offers researchers the
      possibility of conducting individual interviews as well as small focus groups,
      comparable to onsite types. This commentary presents the characteristics of the
      Skype interview as an alternative or supplemental choice to investigators who
      want to change their conventional approach of interviewing. 

PMID- 24746248
TI  - Differences in health and well-being for parents of children with disabilities.

PMID- 24746249
TI  - School situation for children with disabilities--how can we as qualitative
      researchers contribute?

PMID- 24746250
TI  - Evaluating performance of biomedical image retrieval systems--an overview of the
      medical image retrieval task at ImageCLEF 2004-2013.
AB  - Medical image retrieval and classification have been extremely active research
      topics over the past 15 years. Within the ImageCLEF benchmark in medical image
      retrieval and classification, a standard test bed was created that allows
      researchers to compare their approaches and ideas on increasingly large and
      varied data sets including generated ground truth. This article describes the
      lessons learned in ten evaluation campaigns. A detailed analysis of the data also
      highlights the value of the resources created. 

PMID- 24746251
TI  - Prevalence of visual impairment and blindness in Upper Egypt: a gender-based
      perspective.
AB  - PURPOSE: To estimate the prevalence, causes of and risk factors for vision loss
      in Upper Egypt. METHODS: In this cross-sectional study, four villages in Upper
      Egypt were randomly selected; within these four villages, households were
      randomly selected and within the selected households all residents aged >= 40
      years were enumerated and enrolled. Door-to-door eye examinations of household
      members were conducted. Data on relevant demographic and socioeconomic
      characteristics were collected. The prevalence and causes of vision loss and
      associated risk factors were assessed. Sex differences in prevalence and
      determinants were also evaluated. RESULTS: The prevalence of best eye presenting
      visual impairment, severe visual impairment, and blindness were 23.9%, 6.4%, and
      9.3% respectively. The prevalence of blindness among women significantly exceeded
      that among men (11.8% vs. 5.4%, respectively, p = 0.021). The prevalence of
      cataract was 22.9% (higher in women, 26.5% than men 17.2%, p = 0.018). The
      prevalence of trachomatous trichiasis was 9.7% (higher among women, 12.5%, than
      men, 5.4%, p = 0.012). The principal causes of blindness were cataract (60%),
      uncorrected refractive errors (16%) and corneal opacities (12%). Age, sex, family
      size, illiteracy, unemployment, water source and sanitation methods and living
      conditions were the major risk factors for vision loss. CONCLUSION: The
      prevalence of visual impairment remains high in Egypt, particularly among women.
      Risk factors for blindness may differ between men and women. There is a need for
      qualitative investigations to better understand the causes behind the excess in
      prevalence of blindness among women.

PMID- 24746252
TI  - Layperson trauma training in low- and middle-income countries: a review.
AB  - BACKGROUND: Prehospital trauma systems are rudimentary in many low- and middle
      income countries (LMICs) and require laypersons to stabilize and transport
      injured patients. The World Health Organization recommends educating layperson
      first responders as an essential step in the development of Emergency Medical
      Services systems in LMICs. This systematic review examines trauma educational
      initiatives for layperson first responders in resource-poor settings. MATERIALS
      AND METHODS: Layperson first-responder training and education program
      publications were identified using PubMed MEDLINE and Scopus databases. Articles
      addressing physicians, professional Emergency Medical Services training, or
      epidemiologic descriptions were excluded. Publications were assessed by
      independent reviewers, and those included underwent thematic analysis. RESULTS:
      Thirteen publications met inclusion criteria. Four themes emerged regarding the
      development of layperson first-responder training programs: (1) An initial needs
      assessment of a region's existing trauma system of care and laypersons' baseline
      emergency care knowledge focuses subsequent educational interventions; (2)
      effective programs adapt to and leverage existing resources; (3) training methods
      should anticipate participants with low levels of education and literacy; and (4)
      postimplementation evaluation allows for curriculum improvement. Technology, such
      as online and remote learning platforms, can be used to operationalize each
      theme. CONCLUSIONS: Successful training programs for layperson first responders
      in LMICs identify and maximize existing resources are adaptable to learners with
      little formal education and are responsive to postimplementation evaluation.
      Educational platforms that leverage technology to deliver content may facilitate
      first-responder trauma education in underresourced areas. Themes identified can
      inform the development of trauma systems of care to decrease mortality and
      physiological severity scores in trauma patients in LMICs.

PMID- 24746253
TI  - Matrix metalloproteinase levels in chronic thoracic aortic dissection.
AB  - BACKGROUND: Imbalance between matrix metalloproteinases (MMPs) and tissue
      inhibitors of MMPs (TIMPs) can lead to aortic wall failure. We hypothesized that
      patients with aneurysms resulting from chronic descending thoracic aortic
      dissection have elevated tissue and plasma levels of specific MMPs and decreased
      tissue levels of TIMPs. MATERIALS AND METHODS: Aortic tissue was obtained from 25
      patients who required surgical repair of descending thoracic aortic aneurysm due
      to chronic aortic dissection and from 17 organ-donor controls without aortic
      disease. Tissue levels of MMP-1, -2, -3, -9, -12, and -13 and TIMP-1 and -2 were
      measured by colorimetric activity assay or enzyme-linked immunosorbent assay and
      confirmed by Western blot and immunohistochemistry. Blood obtained from the 25
      patients and 15 controls without aortic diseases was used to compare plasma
      levels of MMP-3, -9, and -12. RESULTS: Total MMP-1, total MMP-9, and active MMP-9
      levels were higher and total MMP-2 levels were lower in dissection tissue than in
      control tissue. Additionally, the MMP-9 to TIMP-1 and active to total MMP-2
      ratios were higher and the MMP-2 to TIMP-2 ratio was lower in dissection tissue.
      Furthermore, patients had higher plasma active to total MMP-9 ratios than the
      controls. Age and hypertension were associated with increased MMP levels.
      CONCLUSIONS: Increased levels of several MMPs and increased MMP to TIMP ratios in
      aortic tissue from patients suggest an environment that favors proteolysis, which
      may promote progressive extracellular matrix destruction and medial degeneration
      after aortic dissection. An elevated active to total MMP-9 ratio in plasma may be
      a biomarker for end-stage aneurysm development in patients with chronic thoracic
      aortic disease.

PMID- 24746254
TI  - Primary closure after laparoscopic common bile duct exploration versus T-tube.
AB  - BACKGROUND: Laparoscopic common bile duct exploration (LCBDE) is now one of the
      main methods for treating choledocholithiasis accompanied with cholelithiasis.
      The objective of our study was to assess the safety and effectiveness of
      laparoscopic primary closure for the treatment of common bile duct (CBD) stones
      compared with T-tube drainage. METHODS: Patients who underwent CBD stones were
      studied prospectively from 2002-2012 in a single center. A total of 194 patients
      were randomly assigned to group A (LCBDE with primary closure) with 101 cases and
      group B (LCBDE with T-tube drainage) with 93 cases. Intraoperative
      cholangiography and choledochoscopy were performed in all patients. Patient
      demographics, intraoperative findings, postoperative stay, complications, and
      hospital expenses were recorded and analyzed. RESULTS: There was no mortality in
      the two groups. Four patients (3.96%) of group A were converted to open surgery,
      and three patients (3.23%) in group B. The mean operating time was much shorter
      in group A than in group B (102.6 +/- 15.2 min versus 128.6 +/- 20.4 min, P <
      0.05). The length of postoperative hospital stay was longer in group B (4.9 +/-
      3.2 d) than in group A (3.2 +/- 2.1 d). The hospital expenses were significantly
      lower in group A. Three patients experienced postoperative complications, which
      were related to the usage of the T-tube in group B. The incidences of overall
      postoperative complications were insignificantly lower in group A. CONCLUSIONS:
      Laparoscopic primary closure of CBD is safe and effective for the management of
      CBD stones, and can be performed routinely as an alternative to T-tube drainage.

PMID- 24746255
TI  - Duty hours and perceived competence in surgery: are interns ready?
AB  - BACKGROUND: A fundamental shift in the structure of many surgical training
      programs has occurred after the July 2011 rule changes. Our intern didactic
      program was intensified in 2011 with targeted lectures, laboratories, and
      clinical cases as well as direct supervision until competency was achieved for
      basic clinical problems. We sought to compare interns' perceived preparedness
      throughout and at the end of the academic years before and after July 2011.
      MATERIALS AND METHODS: Intern perceptions of preparedness to manage common
      clinical scenarios and perform procedures in general surgery were serially
      surveyed in academic years ending in 2011 and 2012 based on the Residency Review
      Committee supervision guidelines. RESULTS: Interns felt less prepared across all
      measured domains from 2011-2012. Interns felt significantly less prepared to
      manage hypotension (3.00/4 points to 2.67/4 points; P=0.04), place a tube
      thoracostomy (2.45/4 points to 1.92/4 points; P=0.04), or perform an inguinal
      hernia repair (1.91/4 points to 0.92/4 points; P=0.01) without supervision.
      Interns were also significantly less likely to agree that they were able to gain
      clinical skills based on experience (4.31/5 points versus 4.15/5 points; P=0.02).
      Longitudinal analysis throughout internship demonstrated improved preparedness to
      manage common clinical problems and perform procedures between the second and the
      fifth months of internship. CONCLUSIONS: First-year residents after July 2011
      felt less prepared in the topics surveyed than those before July 2011. Interns
      made the greatest gains in preparedness between months 2 and 5, suggesting that
      despite planned interventions, no substitute currently exists for actual clinical
      experience. Planned educational interventions to improve intern preparedness are
      also indicated.

PMID- 24746256
TI  - Online patient resources for hernia repair: analysis of readability.
AB  - BACKGROUND: The limited functional health literacy of a significant portion of
      the adult US population negatively affects their access to appropriate online
      health information about hernia repair surgery. The National Institutes of Health
      and American Medical Association recommend that patient-directed content should
      be written at a sixth-grade reading level. This study aims to evaluate
      readability of the most frequently used Internet resources for patient
      information about hernia repair relative to average American literacy. METHODS: A
      web search for "hernia repair surgery" was performed, and the top 12 Web sites
      were identified. Relevant articles (n=102) with patient-directed content
      immediately available from the main sites were downloaded. The 12 most popular
      consumer magazines in circulation were also identified, and using the same
      method, the first 10 articles were downloaded from each magazine's Web site for
      comparison. Readability was assessed using 10 established analyses. A t-test was
      used to compare the average grade level of hernia repair and magazine articles
      for each readability test. RESULTS: Web-based information about hernia repair had
      an overall average reading grade level of 13.6. All 102 articles were above the
      recommended sixth-grade reading level; these were significantly more difficult to
      read than the comparison group of articles from popular magazines. CONCLUSIONS:
      Online patient-directed information about hernia repair uniformly exceeds the
      recommended reading level and may be too difficult to be understood by a large
      portion of the US population.

PMID- 24746257
TI  - Vibrational spectroscopy of the water-nitrate complex in the O-H stretching
      region.
AB  - The vibrational spectroscopy of the nitrate-water isotopologues is studied in the
      O-H and O-D stretching regions using temperature-dependent infrared multiple
      photon dissociation spectroscopy combined with calculations of the anharmonic
      spectra. At a temperature of 15 K a series of discrete peaks is observed in the
      IRMPD spectra of NO3(-).H2O, NO3(-).HDO, and NO3(-).D2O. This structure is
      considerably more complex than predicted by harmonic calculations. A signal is
      only observed in the hydrogen-bonded O-H (O-D) stretching region, characteristic
      of a double hydrogen-bond donor binding motif. With increasing temperature, the
      peaks broaden, leading to a quasi-continuous absorption from 3150 to 3600 cm(-1)
      (2300-2700 cm(-1)) for NO3(-).H2O (NO3(-).D2O) and, above 100 K, an additional
      band in the free O-H (O-D) stretching region, suggesting the population of
      complexes containing only a single hydrogen bond at higher internal energies.
      Vibrational configuration interaction calculations confirm that much of the
      structure observed in the IRMPD spectra derives from progressions in the water
      rocking mode resulting from strong cubic coupling between the O-H (O-D) stretch
      and water rock degrees of freedom. The spectra of both NO3(-).H2O and NO3(-).D2O
      display a strong peak that does not derive from the water rock progression but
      results instead from a Fermi resonance between the O-H (O-D) stretch and H-O-H (D
      O-D) bend overtone. Additional insight into the nature of the O-H (O-D) stretch
      and water rocking coupling in these complexes is provided by an effective
      Hamiltonian that allows for the cubic coupling between the O-H stretch and water
      rock degrees of freedom. 

PMID- 24746258
TI  - Paravertebral extramedullary hematopoiesis.

PMID- 24746259
TI  - Acylated flavonol glycosides from the flower of Elaeagnus angustifolia L.
AB  - Seven acylated flavonol glycosides named elaeagnosides A-G, in addition to seven
      known flavonoids were isolated from the flowers of Elaeagnus angustifolia. Their
      structures were elucidated by different spectroscopic methods including 1D, 2D
      NMR experiments and HR-ESI-MS analysis. In order to identify natural antioxidant
      and tyrosinase inhibitor agents, the abilities of these flavonoids to scavenge
      the 1,1-diphenyl-2-picrylhydrazyl radical (DPPH) and to inhibit tyrosinase
      activity were evaluated. Results revealed that two of these compounds had
      significant anti-oxidant effect and one compound showed weak tyrosinase
      inhibitory activity compared with kojic acid, quercetin, or ascorbic acid, which
      were used as positive control. 

PMID- 24746260
TI  - Mindfulness-oriented meditation improves self-related character scales in healthy
      individuals.
AB  - Previous studies have shown that mindfulness meditation may improve well-being in
      healthy individuals and be effective in the treatment of mental and neurological
      disorders. Here, we investigated the effects of an 8-week mindfulness-mediation
      program on the personality profiles of three groups of healthy individuals with
      no previous experience with meditation as compared to a control group not
      enrolled in any training. Personality profiles were obtained through the
      Temperament and Character Inventory (Cloninger et al., 1993). In the experimental
      groups, significant increments after the training were obtained in all the three
      character scales describing the levels of self maturity at the intrapersonal
      (Self-Directedness), interpersonal (Cooperativeness), and transpersonal (Self
      Transcendence) levels. No changes were found in the control group. Strikingly,
      these effects were significant only in those groups who were engaged in
      consistent daily meditation practice but not in the group who attended the
      meditation training but were less consistent in home practice. Since higher
      scores in the character scales are associated to a lower risk of personality
      disorder, we propose that the increase of self maturity after the training may be
      an important mechanism for the effectiveness of mindfulness-oriented meditation
      in psychotherapeutic contexts.

PMID- 24746261
TI  - S100A6 and its extracellular targets in Wharton's jelly of healthy and
      preeclamptic patients.
AB  - INTRODUCTION: In this work we compared the level, localization and binding
      partners of a calcium binding protein, S100A6, in extracellular matrix of
      Wharton's jelly of healthy and preeclamptic patients. METHODS: Studies were
      performed on the umbilical cords taken from 10 newborns delivered by healthy and
      10 newborns delivered by preeclamptic mothers. To characterize S100A6 in
      Wharton's jelly immunoblotting and immunohistochemistry were applied. For
      identification of S100A6 targets pull down assays and mass spectrometry were
      performed. Direct interaction of S100A6 with its targets was checked by ELISA
      while co-localization of these proteins was analyzed by immunofluorescence
      staining. RESULTS: We have found that the level of S100A6 in Wharton's jelly is
      higher in patients with preeclampsia than in healthy ones and that post
      translational modifications of S100A6 in preeclamptic tissue are different than
      those of S100A6 in control. We have identified several proteins that might
      interact with S100A6, among them are lumican and PRELP, found in Wharton's jelly
      of healthy and preeclamptic patients, and IGFBP-1 identified, as an S100A6
      target, only in preeclamptic tissue. We have shown that the interactions between
      S100A6 and these proteins are direct and that IGF-1 competes with S100A6 for
      binding to IGFBP-1. CONCLUSION: In Wharton's jelly of preeclamptic tissue S100A6
      is up-regulated and binds to different targets than in control. This suggests
      involvement of S100A6 in development of preeclampsia.

PMID- 24746262
TI  - Angiogenic factors at diagnosis of late-onset small-for-gestational age and
      histological placental underperfusion.
AB  - OBJECTIVE: This study was designed to explore the association between angiogenic
      factors levels at diagnosis of small-for-gestational age (SGA) and placental
      underperfusion (PUP). METHODS: In a cohort of SGA singleton pregnancies, each
      delivered at >34 weeks, uterine (UtA), umbilical (UA), and middle cerebral (MCA)
      arteries were evaluated by Doppler upon diagnosis of SGA status. In addition,
      maternal circulating concentrations of placental growth factor (PlGF) and soluble
      fms-like tyrosine kinase-1 (sFlt-1) were assayed by ELISA, and each placenta was
      evaluated for histologic signs of PUP using a hierarchical and standardized
      classification system. Logistic regression was applied to analyze independent
      relationships (at diagnosis) between angiogenic factors and Doppler parameters.
      RESULTS: A total of 122 suspected SGA pregnancies were studied, 70 (57.4%) of
      which ultimately met PUP criteria. In this group, 85 placental findings qualified
      as PUP. Both mean UtA pulsatility index z-values (1.26 vs. 0.84; p = 0.038) and
      PlGF multiples of normal median (0.21 vs. 0.55; p = 0.002) differed significantly
      in pregnancies with and without PUP, respectively. By logistic regression, PlGF
      alone was independently predictive of PUP (OR = 0.11 [95% CI 0.025-0.57]; p =
      0.008). DISCUSSION: Histologic placental abnormalities in term SGA neonates
      reflect latent insufficiency in uteroplacental blood supply. The heightened risk
      of adverse perinatal outcomes in this context underscores a need for new Doppler
      or biochemical prenatal markers of placental disease. Angiogenic factors may be
      pivotal identifying SGA neonates. CONCLUSIONS: Diminished circulating levels of
      placental growth factor, determined upon discovery of SGA status, are associated
      with histologic evidence of PUP.

PMID- 24746263
TI  - Evaluation of different recruitment and randomisation methods in a trial of
      general practitioner-led interventions to increase physical activity: a
      randomised controlled feasibility study with factorial design.
AB  - BACKGROUND: Interventions promoting physical activity by General Practitioners
      (GPs) lack a strong evidence base. Recruiting participants to trials in primary
      care is challenging. We investigated the feasibility of (i) delivering three
      interventions to promote physical activity in inactive participants and (ii)
      different methods of participant recruitment and randomised allocation. METHODS:
      We recruited general practices from Devon, Bristol and Coventry. We used a 2-by-2
      factorial design for participant recruitment and randomisation. Recruitment
      strategies were either opportunistic (approaching patients attending their GP
      surgery) or systematic (selecting patients from practice lists and approaching
      them by letter). Randomisation strategies were either individual or by practice
      cluster. Feasibility outcomes included time taken to recruit the target number of
      participants within each practice. Participants were randomly allocated to one of
      three interventions: (i) written advice (control); (ii) brief GP advice (written
      advice plus GP advice on physical activity), and (iii) brief GP advice plus a
      pedometer to self-monitor physical activity during the trial. Participants
      allocated to written advice or brief advice each received a sealed pedometer to
      record their physical activity, and were instructed not to unseal the pedometer
      before the scheduled day of data collection. Participant level outcomes were
      reported descriptively and included the mean number of pedometer steps over a 7
      day period, and European Quality of Life (EuroQoL)-5 dimensions (EQ-5D) scores,
      recorded at 12 weeks' follow-up. RESULTS: We recruited 24 practices (12 using
      each recruitment method; 18 randomising by cluster, 6 randomising by individual
      participant), encompassing 131 participants. Opportunistic recruitment was
      associated with less time to target recruitment compared with systematic (mean
      difference (days) -54.9, 95% confidence interval (CI) -103.6; -6.2) but with
      greater loss to follow up (28.8% versus. 6.9%; mean difference 21.9% (95% CI
      9.6%; 34.1%)). There were differences in the socio-demographic characteristics of
      participants according to recruitment method. There was no clear pattern of
      change in participant level outcomes from baseline to 12 weeks across the three
      arms. CONCLUSIONS: Delivering and trialling GP-led interventions to promote
      physical activity is feasible, but trial design influences time to participant
      recruitment, participant withdrawal, and possibly, the socio-demographic
      characteristics of participants. TRIAL REGISTRATION NUMBER: ISRCTN73725618.

PMID- 24746270
TI  - Mahorones, highly brominated cyclopentenones from the red alga Asparagopsis
      taxiformis.
AB  - The red alga Asparagopsis taxiformis (Rhodophyta, Bonnemaisoniaceae) has been
      shown to produce a large diversity of halogenated volatile organic compounds,
      with one to four carbons. As the distribution of this alga may expand worldwide,
      we implemented a research program that aims to understand the functions of its
      specialized metabolome in marine ecosystems. Phytochemical investigations
      performed on A. taxiformis gametophyte stages from the Indian Ocean revealed two
      new highly brominated cyclopentenones named mahorone (1) and 5-bromomahorone (2).
      They are the first examples of natural 2,3-dibromocyclopentenone derivatives.
      Their structure elucidation was achieved using spectrometric methods including
      NMR and MS. A standardized ecotoxicological assay was used as an assessment of
      their role in the environment, revealing high toxicities for both compounds (EC50
      0.16 MUM for 1 and 2). Additionally, both compounds were evaluated in
      antibacterial, antifungal, and cytotoxicity assays. Compounds 1 and 2 exhibit
      mild antibacterial activities against the human pathogen Acinetobacter baumannii.

PMID- 24746271
TI  - The role of pacritinib in the management of myelofibrosis.
AB  - The recent discovery of the JAK2 mutation and its role in the pathogenesis of
      myeloproliferative neoplasms led to the development of a novel class of
      therapeutic agents, the oral JAK2 inhibitors. These agents are effective in
      decreasing organomegaly and ameliorating constitutional symptoms in patients with
      myelofibrosis, regardless of the mutational status. Among this new class of
      agents is pacritinib, a dual JAK2 and FLT3 inhibitor that showed evidence of
      clinical efficacy in early-phase trials of patients with myelofibrosis, with
      limited hematologic toxicity. 

PMID- 24746272
TI  - Drug-induced liver injury: what was new in 2013?
AB  - INTRODUCTION: The year 2013 continued to highlight numerous aspects of drug
      induced liver injury (DILI), with new information communicated via > 1500
      publications. New reports of DILI were described and FDA warnings and alerts were
      issued for a number of products, emphasizing the risks related to hepatotoxicity.
      AREAS COVERED: We provide a summary of the year's published reports of new causes
      of DILI, along with reviews and reports of established hepatotoxins, new and
      expanded DILI registries and the continuing emphasis placed on genetic and other
      risk factors. Several new analyses of data generated from the US DILI Network are
      included. EXPERT OPINION: The clinical usefulness of pharmacogenetic testing
      remains to be determined; the number of patients who must be tested is large and
      the overall risk of DILI is quite small. The role that dose and hepatic
      metabolism play in causing idiosyncratic DILI was reviewed; daily doses > 50 -
      100 mg of medications with high lipophilicity appear to be most predictive of
      severe DILI, but not in all cases. Restricting access to paracetamol in certain
      parts of the UK continues to demonstrate a successful reduction in the number of
      acute liver failure cases and patients listed for liver transplant.

PMID- 24746273
TI  - Intravenous cobinamide versus hydroxocobalamin for acute treatment of severe
      cyanide poisoning in a swine (Sus scrofa) model.
AB  - STUDY OBJECTIVE: Hydroxocobalamin is a Food and Drug Administration-approved
      antidote for cyanide poisoning. Cobinamide is a potential antidote that contains
      2 cyanide-binding sites. To our knowledge, no study has directly compared
      hydroxocobalamin with cobinamide in a severe, cyanide-toxic large-animal model.
      Our objective is to compare the time to return of spontaneous breathing in swine
      with acute cyanide-induced apnea treated with intravenous hydroxocobalamin,
      intravenous cobinamide, or saline solution (control). METHODS: Thirty-three swine
      (45 to 55 kg) were intubated, anesthetized, and instrumented (continuous mean
      arterial pressure and cardiac output monitoring). Anesthesia was adjusted to
      allow spontaneous breathing with FiO2 of 21% during the experiment. Cyanide was
      continuously infused intravenously until apnea occurred and lasted for 1 minute
      (time zero). Animals were then randomly assigned to receive intravenous
      hydroxocobalamin (65 mg/kg), cobinamide (12.5 mg/kg), or saline solution and
      monitored for 60 minutes. A sample size of 11 animals per group was selected
      according to obtaining a power of 80%, an alpha of .05, and an SD of 0.17 in mean
      time to detect a 20% difference in time to spontaneous breathing. We assessed
      differences in time to death among groups, using Kaplan-Meier estimation methods,
      and compared serum lactate, blood pH, cardiac output, mean arterial pressure,
      respiratory rate, and minute ventilation time curves with repeated-measures
      ANOVA. RESULTS: Baseline weights and vital signs were similar among groups. The
      time to apnea and cyanide dose required to achieve apnea were similar. At time
      zero, mean cyanide blood and lactate concentrations and reduction in mean
      arterial pressure from baseline were similar. In the saline solution group, 2 of
      11 animals survived compared with 10 of 11 in the hydroxocobalamin and cobinamide
      groups (P<.001 between the 2 treated groups and the saline solution group). Time
      to return of spontaneous breathing after antidote was similar between
      hydroxocobalamin and cobinamide (1 minute 48 seconds versus 1 minute 49 seconds,
      respectively). Blood cyanide concentrations became undetectable at the end of the
      study in both antidote-treated groups, and no statistically significant
      differences were detected between the 2 groups for mean arterial pressure,
      cardiac output, respiratory rate, lactate, or pH. CONCLUSION: Both
      hydroxocobalamin and cobinamide rescued severely cyanide-poisoned swine from
      apnea in the absence of assisted ventilation. The dose of cobinamide was one
      fifth that of hydroxocobalamin.

PMID- 24746274
TI  - Does aminophylline improve survival for out-of-hospital bradyasystolic arrests in
      adults?

PMID- 24746275
TI  - [Liver transplantation as treatment of familial amyloid polyneuropathy in
      patients older than 60 years].
AB  - BACKGROUND AND OBJECTIVE: Familial amyloid polyneuropathy (FAP) is the most
      prevalent type of hereditary systemic amyloidosis. It is an autosomal dominant
      disease characterized by the deposition of an abnormal variant transthyretin. It
      has a worldwide distribution, with localized endemic areas in Portugal, Sweden
      and Japan. In Spain there is an endemic focus, located in Mallorca. Liver
      transplantation is the only curative option for patients with FAP. The aim of
      this study was to describe the clinical and demographic characteristics of
      patients transplanted with a diagnosis of PAF. MATERIAL AND METHOD: Six patients
      with PAF underwent liver transplantation between April 1986 and December 2012.
      RESULTS: The mean age was 57.7+16 years, patients of Spanish origin were older
      than 60 years. All patients had progressive symptoms as mixed polyneuropathy. In
      2 patients, combined heart-liver transplants sequentially were performed. Patient
      survival and graft was 80% at one, 3 and 5 years. CONCLUSIONS: The only effective
      treatment for etiologic PAF is liver transplantation. Early detection is the key
      to the treatment and control, avoiding the irreversible organ damage.

PMID- 24746276
TI  - [A 64-years old woman with ictericia and sensory disturbances].

PMID- 24746277
TI  - Directing neuronal signaling through cell-surface glycan engineering.
AB  - The ability to tailor plasma membranes with specific glycans may enable the
      control of signaling events that are critical for proper development and
      function. We report a method to modify cell surfaces with specific sulfated
      chondroitin sulfate (CS) glycosaminoglycans using chemically modified liposomes.
      Neurons engineered to display CS-E-enriched polysaccharides exhibited increased
      activation of neurotrophin-mediated signaling pathways and enhanced axonal
      growth. This approach provides a facile, general route to tailor cell membranes
      with biologically active glycans and demonstrates the potential to direct
      important cellular events through cell-surface glycan engineering. 

PMID- 24746278
TI  - Regio- and stereoselective intermolecular oxidative phenol coupling in
      Streptomyces.
AB  - Intermolecular oxidative phenol coupling is the main process in nature for the
      formation of atroposelective biaryl compounds. Although well defined in plants
      and fungi, this type of dimerization reaction in bacteria is poorly understood.
      Therefore, the biosynthesis of julichromes, spectomycins, and setomimycin was
      investigated. The monomeric subunits of these biarylic pre-anthraquinones are
      derived from a common polyketidic precursor, yet the coupling reaction proceeds
      in a regioselective manner, with the position of attachment of the two subunits
      depending on the specific streptomycete strain. By using genome analysis and
      deletion experiments, the biosynthetic gene clusters were identified.
      Furthermore, it was established that cytochrome P450 enzymes are fundamentally
      involved during dimerization of the polyketide monomers. 

PMID- 24746279
TI  - The Mediterranean scorpion Mesobuthus gibbosus (Scorpiones, Buthidae):
      transcriptome analysis and organization of the genome encoding chlorotoxin-like
      peptides.
AB  - BACKGROUND: Transcrof toxin genes of scorpion species have been published. Up to
      this moment, no information on the gene characterization of M. gibbosus is
      available. RESULTS: This study provides the first insight into gene expression in
      venom glands from M. gibbosus scorpion. A cDNA library was generated from the
      venom glands and subsequently analyzed (301 clones). Sequences from 177 high
      quality ESTs were grouped as 48 Mgib sequences, of those 48 sequences, 40 (29
      "singletons" and 11 "contigs") correspond with one or more ESTs. We identified
      putative precursor sequences and were grouped them in different categories (39
      unique transcripts, one with alternative reading frames), resulting in the
      identification of 12 new toxin-like and 5 antimicrobial precursors (transcripts).
      The analysis of the gene families revealed several new components categorized
      among various toxin families with effect on ion channels. Sequence analysis of a
      new KTx precursor provides evidence to validate a new KTx subfamily (alpha-KTx
      27.x). A second part of this work involves the genomic organization of three Meg
      chlorotoxin-like genes (ClTxs). Genomic DNA sequence reveals close similarities
      (presence of one same-phase intron) with the sole genomic organization of
      chlorotoxins ever reported (from M. martensii). CONCLUSIONS: Transcriptome
      analysis is a powerful strategy that provides complete information of the gene
      expression and molecular diversity of the venom glands (telson). In this work, we
      generated the first catalogue of the gene expression and genomic organization of
      toxins from M. gibbosus. Our result represents a relevant contribution to the
      knowledge of toxin transcripts and complementary information related with other
      cell function proteins and venom peptide transcripts. The genomic organization of
      the chlorotoxin genes may help to understand the diversity of this gene family.

PMID- 24746281
TI  - The reliability, validity, and usefulness of single-operator cholangioscopy.

PMID- 24746280
TI  - Management of rectal cancers in relation to treatment guidelines: a population
      based study comparing Italian and French patients.
AB  - BACKGROUND: Few studies have investigated rectal cancer management at the
      population level. We compared how rectal cancers diagnosed in Italy (2003-2005)
      and France (2005) were managed, and evaluated the extent to which management
      adhered to European guidelines. METHODS: Samples of 3938 Italian and 2287 French
      colorectal cancer patients were randomly extracted from 8 and 12 cancer
      registries respectively. Rectal cancer patients (860 Italian, 559 French) were
      analysed. Logistic regression models estimated odds ratios (ORs) of being treated
      with curative intent, receiving sphincter-saving surgery, and receiving
      preoperative radiotherapy. RESULTS: Similar proportions of Italian and French
      patients were treated with curative intent (70% vs. 67%; OR=0.92 [0.73-1.16]);
      the respective proportions receiving sphincter-saving surgery were 21% and 33%
      (OR=1.15 [0.86-1.53]). In about 50% of those treated with curative intent, >= 12
      lymph nodes were harvested in both countries. The proportion receiving
      postoperative radiotherapy was higher in Italy than in France (25% vs. 11%,
      p<0.01), but French patients were more likely to receive preoperative
      radiotherapy (52% vs. 21%; OR=4.06 [2.79-5.91]). CONCLUSION: The proportions of
      patients receiving preoperative radiotherapy and the numbers of lymph nodes
      sampled were low in both countries. Centralising treatment and potentiating
      screening would be practical ways of improving outcomes and adhering to
      guidelines.

PMID- 24746282
TI  - Skin stretching for primary closure of acute burn wounds.
AB  - BACKGROUND: In burn care, a well-acknowledged problem is the suboptimal scar
      outcome from skin grafted burn wounds. With the aim of improving this, we focused
      on a new technique: excision of the burn wound followed by primary closure,
      thereby using a skin-stretching device to stretch the adjacent healthy skin. The
      short- and long-term effect of Skin Stretch was compared to split skin grafting
      (SSG) in a randomized controlled trial. METHODS: Patients with burn wounds were
      randomized for SSG or primary wound closure using Skin Stretch. Follow-up was
      performed at 3 and 12 months postoperatively. The scar surface area was
      calculated and the scar quality was assessed, using subjective and objective
      measurement methods. RESULTS: No significant differences between the SSG and the
      Skin Stretch group were found for scar surface area. In the Skin Stretch group, a
      significant reduction of the surface area from 65.4cm(2) (13.6-129.1) to
      13.4cm(2) (3.0-36.6) was found at 3 months (p=0.028) and at 12 months
      postoperatively (65.4cm(2) (13.6-129.1) to 33.0cm(2) (8.9-63.7), p=0.046,
      Wilcoxon signed ranks test). CONCLUSIONS: Skin Stretch for primary closure of
      acute burn wounds is a suitable technique and can be considered for specific
      circumscript full-thickness burn wounds. However, future research should be
      performed to provide additional scientific evidence.

PMID- 24746283
TI  - Key factors in patient-centered care coordination in ambulatory care: nurse care
      coordinators' perspectives.
AB  - BACKGROUND: Care coordination within Health Care Homes (HCHs) is an evolving
      registered nurse role. The purpose of this study was to identify factors
      influencing nurse care coordination. AIMS: The aims are to 1) describe the
      characteristics of patients perceived by nurse care coordinators (NCCs) to
      benefit from care coordination and to 2) describe interventions judged by NCCs to
      be most effective in caring for patients with complex chronic care needs.
      METHODS: This study was an analysis of existing data using a qualitative
      descriptive design. Experienced NCCs from various practice settings participated
      in a focus group. Data were analyzed using content analysis. RESULTS: Findings
      indicate the importance of the cumulative impact of complex health problems,
      limited social support, culture and language on patients needing care
      coordination. Effective interventions are focused on providing holistic,
      relationship-based care. CONCLUSION: The identification of contextual factors
      juxtaposed to complex chronic health conditions holds promise as a powerful
      indicator of individuals needing targeted, individualized interventions.

PMID- 24746284
TI  - Sleep, health-related quality of life, and functional outcomes in adults with
      diabetes.
AB  - PURPOSE: This study explored the association of sleep quality with physical and
      mental health-related quality of life (HRQoL) and functional outcomes in 116
      participants with type 2 diabetes. METHODS: The study is a secondary analysis of
      baseline data from a clinical trial that examined treatment of obstructive sleep
      apnea on physical activity and glucose control. Instruments included the
      Pittsburgh Sleep Quality Index, Medical Outcomes Short-Form Physical Component
      and Mental Component Scores, and Functional Outcomes of Sleep Questionnaire.
      RESULTS: Higher physical HRQoL was significantly associated with better sleep
      quality and improved functional outcomes of increased activity and productivity.
      Higher mental HRQoL was associated with improved sleep quality and improved
      functional outcomes of increased activity, social interactions, vigilance, and
      productivity. Poor sleep quality was a predictor of decreased functional outcomes
      while controlling for age, race, education, BMI, marital status and physical and
      mental HRQoL. CONCLUSION: Poor sleep quality is associated with negative
      physical, mental, and functional outcomes in adults with type 2 diabetes.

PMID- 24746285
TI  - One-pot synthesis of 4-substituted 3-amino-2-cyanothiophenes involving O-ethyl
      thioformate.
AB  - An efficient one-pot synthesis of 4-substituted 3-amino-2-cyanothiophenes is
      described. Treatment of 2-alkyl or aryl substituted acetonitrile sequentially
      with 2.1 equiv of LDA, 1.1 equiv of O-ethyl thioformate, and 1.2 equiv of 2
      chloroacetonitrile afforded the thiophenes in moderate to good yields. The
      thiophene core can be readily incorporated into more elaborate pharmaceutically
      relevant structures as demonstrated by converting 3-amino-2-cyano-4
      phenylthiophene (1g) to various functionalized thieno[3,2-d]pyrimidines in only
      two steps. 

PMID- 24746286
TI  - Mental health outreach and street policing in the downtown of a large French
      city.
AB  - CONTEXT: Marseille, the second largest city in France, has a large population of
      homeless persons. A mental health outreach team was created in 2005 as a response
      to high rates of mental illness among this group. In a national political context
      where security is a government priority, a new central police station was created
      in Marseille in 2006 to address robberies, violence and illegal traffic in the
      downtown area of the city. While not directly related to such crimes, police also
      are responsible for public safety or behavioral issues related to the presence of
      individuals who are homeless in this area. OBJECTIVE: This report on a two-year
      pilot study (2009-2011) addresses collaborative work between a mental health
      outreach team and the police department responding to the clinical needs of
      persons who are homeless with serious psychiatric disorders. It also describes
      the homeless persons' interactions with, and perceptions of the presence of,
      police and mental health professionals on the streets. METHODS: Investigators
      adopted a mixed-methods approach. Data were collected on 40 interactions using
      brief standardized report for each interaction. Focus groups were conducted with
      police officers, outreach team members, peer workers, and service users. Minutes
      of partnership meetings between police officers and outreach workers also served
      as a source of qualitative data. RESULTS: Outreach workers initiated just over
      half (n=21) of the encounters (n=40) between police and outreach workers.
      Interactions mainly involved persons with psychosis (77%), the vast majority
      (80%) of which involved persons in an acute phase of psychosis. Two key themes
      that emerged from data analysis included the violent nature of life on the
      streets and the high percentage of ethnic minorities among subjects of the
      interactions. In addition, it was found that the practices of the outreach
      workers are sometimes similar to those of the police, especially when outreach
      workers use coercive methods. "Users" (homeless persons) described police as
      sometimes using less coercion than the outreach team, and noted that they were
      more fearful of psychiatrists than police. CONCLUSION: Formal initiatives between
      mental health outreach teams and police departments involve some common street
      practices. This study demonstrates the potential for closer working relationships
      between the two parties to help persons who are homeless with mental illnesses
      receive needed care, and to reduce inappropriate coercion including involuntary
      hospitalization and arrests.

PMID- 24746287
TI  - Genetic variability of Eucoleus aerophilus from domestic and wild hosts.
AB  - Eucoleus aerophilus (syn. Capillaria aerophila) is a trichuroid nematode
      affecting domestic and wild carnivores and, sometimes, humans. This parasite has
      a worldwide distribution and may cause significant clinical disease in pet
      animals. The present paper investigates the sequence variation in partial
      mitochondrial cytochrome c oxidase subunit 1 (cox1) gene of E. aerophilus
      isolates from pets and wild animals from different countries. Forty-four egg
      pools of E. aerophilus were collected from dogs, cats and foxes from Italy, while
      seventeen adult stages of E. aerophilus were obtained from red foxes and beech
      martens from Portugal, Romania, Serbia and UK. Fifteen different haplotypes were
      characterized and five were shared between pets in Italy and wildlife from
      Europe. The remaining haplotypes were either confined only in hosts or countries,
      or in a given host from a country. The phylogenetic analysis showed that all
      haplotypes clustered as a monophyletic group with a strong nodal support,
      indicating that all sequence types represented E. aerophilus. The results here
      presented have implications for a better understanding of the epidemiology, phylo
      geography and clinical impact of E. aerophilus. In particular, the geographic
      distribution of E. aerophilus haplotypes in different host species and geographic
      regions, and their variation in terms of pathogenic impact and zoonotic role,
      warrant further investigations.

PMID- 24746288
TI  - Transcriptomic profiling as a screening tool to detect trenbolone treatment in
      beef cattle.
AB  - The effects of steroid hormone implants containing trenbolone alone (Finaplix-H),
      combined with 17beta-oestradiol (17beta-E; Revalor-H), or with 17beta-E and
      dexamethasone (Revalor-H plus dexamethasone per os) on the bovine muscle
      transcriptome were examined by DNA-microarray. Overall, large sets of genes were
      shown to be modulated by the different growth promoters (GPs) and the regulated
      pathways and biological processes were mostly shared among the treatment groups.
      Using the Prediction Analysis of Microarray program, GP-treated animals were
      accurately identified by a small number of predictive genes. A meta-analysis
      approach was also carried out for the Revalor group to potentially increase the
      robustness of class prediction analysis. After data pre-processing, a high level
      of accuracy (90%) was obtained in the classification of samples, using 105
      predictive gene markers. Transcriptomics could thus help in the identification of
      indirect biomarkers for anabolic treatment in beef cattle to be applied for the
      screening of muscle samples collected after slaughtering.

PMID- 24746289
TI  - Capsaicin-induced neurogenic inflammation in pig skin: a behavioural study.
AB  - Topical capsaicin is a well-established model of experimental hyperalgesia. Its
      application to the study of animals has been limited to few species. The effect
      of topical capsaicin on hyperalgesia in porcine skin was evaluated as part of a
      study of inflammatory pain in the pig. Two experiments were carried out on pigs
      of 27 +/- 5 kg (n = 8) and 57 +/- 3 kg (n = 16). Thermal and mechanical noxious
      stimuli were provided (CO2 laser and Pressure Application Measurement device) to
      assess avoidance behaviours. Capsaicin induced significant thermal hyperalgesia
      in the smaller pigs (P < 0.05), while no mechanical hyperalgesia was observed in
      either animal group. The present model of topical capsaicin application may be
      useful to investigate the mechanisms of primary hyperalgesia in this species,
      although some experimental conditions, such as the administration route and
      cutaneous morphology, need to be evaluated.

PMID- 24746290
TI  - Pharmacokinetics of the individual enantiomer S-(+)-ketoprofen after intravenous
      and oral administration in dogs at two dose levels.
AB  - The pharmacokinetic of the individual S-(+)-enantiomer of ketoprofen, S-(+)
      ketoprofen, after intravenous (IV) and oral (PO) administration was determined in
      six dogs at 1 and 3 mg/kg. Plasma concentrations were determined by high
      performance liquid chromatography with ultraviolet detection. The concentration
      time curves were analyzed by non-compartmental methods. Steady-state volume of
      distribution (Vss) and clearance (Cl) of S-(+)-ketoprofen after IV administration
      were 0.22 +/- 0.07 and 0.19 +/- 0.03 L/kg, and 0.10 +/- 0.02 and 0.09 +/- 0.01
      L/h/kg, at 1 and 3 mg/kg, respectively. Following PO administration, S-(+)
      ketoprofen achieved maximum plasma concentrations of 4.91 +/- 0.76 and 12.47 +/-
      0.62 MUg/ml, at two dose levels, respectively. The absolute bioavailability after
      PO route was 88.66 +/- 12.95% and 85.36 +/- 13.90%, respectively.

PMID- 24746291
TI  - Inherited manganism: the "cock-walk" gait and typical neuroimaging features.
AB  - Manganese (Mn) toxicity causes an extrapyramidal, parkinsonian-type movement
      disorder with characteristic magnetic resonance images of Mn accumulation in the
      basal ganglia. This letter highlights the neurological manifestations and
      neuroimaging features of inherited manganism (IMn), an unusual and treatable
      inborn error of Mn homeostasis. Early-onset dystonia with "cock-walk" gait and
      hyperintense signal in basal ganglia, associated to polycythemia, chronic liver
      disease and hypermanganesemia, promptly suggest IMn, and a genetic evaluation
      should be performed. 

PMID- 24746292
TI  - Favorable outcome after withdrawal of immunosuppressant therapy in progressive
      multifocal leukoencephalopathy after renal transplantation: case report and
      literature review.
AB  - Progressive multifocal leukoencephalopathy (PML) is a fatal demyelinating disease
      caused by the JC polyomavirus (JCV). Most patients with PML after renal
      transplantation have had poor outcomes. We describe a patient with PML after
      renal transplantation who had a good response to the withdrawal of
      immunosuppressant therapy. We performed quantitative real-time PCR testing for
      JCV DNA in cerebrospinal fluid (CSF), and assessed mutation of the JC virus
      genome detected in the CSF. At the same time, we checked cranial magnetic
      resonance imaging (MRI). Immunosuppressant therapy was discontinued immediately.
      The MRI scan that followed showed markedly decreased numbers of high intensity
      signals, and the results of real-time PCR for JCV DNA in CSF became negative. The
      patient had no other neurological deficits. Withdrawal of immunosuppressant
      treatment has a beneficial effect on the course of PML after renal
      transplantation, and quantitative PCR may facilitate the immediate withdrawal of
      immunosuppressant agents.

PMID- 24746293
TI  - Polyclonal serum IgM level identifies a subgroup of multiple myeloma patients
      with low-risk clinicobiological features and superior survival.
AB  - Normal plasma cells (PCs) are either undetectable or outnumbered by the
      myelomatous PC compartment in bone marrow of multiple myeloma (MM). However,
      residual normal PCs have been detected in a minority of symptomatic MM patients
      with superior survival. The number of normal PCs is also an important factor to
      identify monoclonal gammopathy of undetermined significance (MGUS)-like MM. We
      speculate that the polyclonal serum IgM level in non-IgM myelomas may reflect the
      number of residual normal PCs. Here we investigated the prognostic relevance of
      polyclonal serum IgM level in a series of 485 newly diagnosed symptomatic MM
      (NDMM) patients. Our results showed that symptomatic MM patients with polyclonal
      IgM more than 0.5g/L displayed a favorable baseline clinical feature, together
      with a significantly lower frequency of high-risk cytogenetic abnormalities. This
      group of patients had a significantly prolonged progression-free survival (PFS)
      and overall survival (OS) regardless of thalidomide or bortezomib therapy.
      Furthermore, the superior outcome was independent of the depth of response. Our
      findings suggest that polyclonal IgM level is capable of identifying a group of
      symptomatic MM patients with distinct clinicobiological characteristics and
      favorable survival, similar with MGUS-like MM. 

PMID- 24746295
TI  - Social media impact factor: the top ten dermatology journals on Facebook and
      Twitter.
AB  - Academic journals are mainly rated according to their impact factors. However,
      considering the enormous worldwide impact of social media, journals and potential
      authors may want to take social media impact into account. 

PMID- 24746294
TI  - Elevated TIM3+ hematopoietic stem cells in untreated myelodysplastic syndrome
      displayed aberrant differentiation, overproliferation and decreased apoptosis.
AB  - TIM3, as a negative regulator of anti-tumor immunity, is highly expressed on
      LSCs, but not on normal HSCs. TIM3 on HSCs in MDS patients has not been
      clarified. Here, both the percentage of TIM3 on HSCs and the MFI of TIM3+ HSCs
      were higher in untreated MDS than control and were closed to AML, and excessive
      TIM3+ HSCs was closely related to clinical parameters: WPSS score, karyotype
      analysis, morphologic blasts, the number of cytopenia involving hematopoietic
      lineages, anemia and granulocytopenia. TIM3+ HSCs expressed lower CD11b, TpoR,
      EpoR, G-CSFR and Annexin V, and higher CD71 and GATA2. TIM3+ HSCs displayed
      aberrant differentiation, overproliferation and decreased apoptosis. TIM3 might
      be a promising marker for identifying malignant clone cells in MDS and a
      candidate for targeted therapy. 

PMID- 24746296
TI  - Amyloidosis cutis dyschromia: a rare form of primary cutaneous amyloidosis.
AB  - Amyloidosis cutis dyschromia is a rare form of primary cutaneous amyloidosis.
      Amyloid deposition in the skin occurs without systemic manifestations and
      produces hypopigmented and hyperpigmented macules. A 19-year-old woman is
      presented with progression of this condition over 16 years. 

PMID- 24746297
TI  - Solitary papule over scalp.
AB  - Folliculosebaceous cystic hamartoma (FSCH) is a rare cutaneous hamartoma
      characterized by follicular, sebaceous, and mesenchymal elements.
      Folliculosebaceous cystic hamartoma is probably not as rare as previously thought
      and its inclusion in the differential diagnosis of asymptomatic skin colored
      papules or nodules is warranted, especially if it is present in the head and neck
      region. 

PMID- 24746298
TI  - Syringocystadenocarcinoma papilliferum with locoregional metastases.
AB  - Syringocystadenocarcinoma papilliferum (SCACP) is a rare malignant counterpart of
      syringocystadenoma papilliferum (SCAP). To date, less than 30 cases have been
      reported, and of those, only three had locoregional metastases [1,2]. Herein, we
      report a case of a 42-year-old man with a rapidly growing nodule on his right
      parietal scalp ultimately diagnosed as SCACP arising in association with a
      preexisting SCAP and nevus sebaceus. This case differs from prior reports in the
      tumor's rapid growth and aggressive course with the development of locoregional
      metastases within 5-weeks from initial presentation. 

PMID- 24746299
TI  - A case of bullous erythema ab igne accompanied by anemia and subclinical
      hypothyroidism.
AB  - Erythema ab igne (EAI) is a dermatosis characterised by reticulate red-brown
      pigmentation and telengiectasia resulting from long-term exposure to infrared
      radiation. It generally occurs in individuals using heating devices in the
      winter, those who frequently use hot compresses, and those who prefer hot
      environments. It generally occurs on the feet of women but may also occur on the
      hips and thighs. A 42-year-old male presented with red-brown spots and blisters
      on both thighs and behind the legs. He was diagnosed with EAI based on the
      clinical, historical, and histopathological features presented. Herein we present
      a case of bullous EAI associated with normochromic normocytic anemia and
      subclinical hypothyroidism. 

PMID- 24746300
TI  - Pigmented Bowen's disease of the penis and scrotum in a patient with AIDS.
AB  - Patients with HIV have higher risk of developing squamous cell carcinoma of the
      skin given the increased risk of HPV infection, which alters cell proliferation
      and apoptosis [1]. Pigmented Bowen's disease is an uncommon form of squamous cell
      carcinoma in-situ characterized by pigmented lesions that can clinically mimic
      superficial spreading melanoma, pigmented basal cell carcinoma, melanocytic
      nevus, Bowenoid papulosis, and seborrheic keratosis. 

PMID- 24746301
TI  - Multiple lentigines in areas of resolving psoriatic plaques after ustekinumab
      therapy.
AB  - The development of lentigines in areas previously involved by psoriasis has been
      reported in the literature, classically related to phototherapy but also to
      topical products. More recently, some authors have described several cases of
      lentigines appearing in resolving psoriatic plaques during or after treatment
      with anti-tumour necrosis factor (TNF) drugs used to treat severe plaque
      psoriasis, including adalimumab, etanercept, and infliximab. We report the case
      of a patient that developed multiple lentigines after clearance of the plaques of
      psoriasis receiving treatment with ustekinumab for his psoriasis. 

PMID- 24746302
TI  - Primary milia localized to the vulva.
AB  - Multiple primary milia were found on the vulva of a 52-year-old woman who was
      referred to the dermatology clinic by her gynecologist. These lesions are
      commonly distributed on the face and rarely occur in this location without
      antecedent trauma. This report demonstrates the unique presentation of primary
      milia in the genital region and explores the diagnostic features and treatment
      methods of these lesions.

PMID- 24746303
TI  - Follicular unit extraction with the Artas robotic hair transplant system system:
      an evaluation of FUE yield.
AB  - Hair transplants were developed and championed by dermatologists. However,
      dermatology literature has few contributions from within our specialty. In this
      manuscript, we present our evaluation of a specific graft harvesting approach for
      hair transplants referred to as Follicular unit extraction (FUE). In particular,
      we sought to evaluate the rate of harvest attempts that did not produce an actual
      hair folliclular unit graft. 

PMID- 24746304
TI  - Secondary mucinous carcinoma of the skin.
AB  - We report a case of a woman who presented with a cystic-appearing nodule on her
      left nipple. After cutaneous biopsy and gynecological staging study, she was
      diagnosed with skin invasion of mucinous carcinoma of the breast. We describe the
      main features of this rare tumor and the controversies in its diagnosis because
      primary and metastatic mucinous carcinomas in skin are histologically
      indistinguishable. 

PMID- 24746305
TI  - Top dermatologic diagnoses by age.
AB  - BACKGROUND: Although some skin conditions predominate in patients of certain
      ages, little data exists about the relative prevalence of dermatologic conditions
      by age. OBJECTIVES: To determine the common skin conditions by age group in the
      United States, both in dermatologist samples and for all specialties. METHODS:
      The National Ambulatory Medical Care Survey (NAMCS) was queried for top diagnoses
      at dermatologist and all skin disease visits from 1993-2010. ICD-9 coding was
      used for diagnoses. RESULTS: There were 588 million estimated visits to
      dermatologists in the US from 1993-2010. Atopic dermatitis, acne, and actinic
      keratosis were the top diagnoses in all age groups. Common diagnoses in all
      groups included contact dermatitis and benign neoplasm. There were 740 million
      estimated skin disease visits to all physicians; more of these were acute or
      infectious. The percent of skin diseases seen by dermatologists gradually
      increased with age to a maximum of 55% in the 75-84 year age group. CONCLUSION:
      Dermatologic conditions seen in different age groups and between dermatologists
      and non-dermatologists vary. With advancing age, Americans increasingly seek a
      dermatologist rather than a non-dermatologist physician for skin conditions.

PMID- 24746306
TI  - Lymphomatoid papulosis and recurrent transitional cell carcinoma of the bladder:
      a paraneoplastic association.
AB  - Lymphomatoid papulosis is a rare, papulonodular skin eruption with histologic
      features of a CD30+ T cell lymphoma. We present a 79-year-old man with
      lymphomatoid papulosis and transitional cell carcinoma of the bladder. 

PMID- 24746307
TI  - Edematous lip in a HIV patient on highly active antiretroviral therapy.
AB  - A 59-year-old HIV-positive, hepatitis C positive man on highly active
      antiretroviral therapy presented with a 2-year history of extreme swelling of the
      lower lip. Granulomatous cheilitis was diagnosed. 

PMID- 24746308
TI  - A perforating pilomatricomal horn on the arm of an 11-year-old girl.
AB  - Cutaneous horns are uncommon in adults and rare in the pediatric population.
      Although verruca vulgaris, solar keratosis, and squamous cell carcinoma are more
      common entities that can present as cutaneous horns in the general population,
      conditions such as molluscum contagiosum, juvenile xanthgranuloma, and pyogenic
      granuloma have been reported causes in the pediatric population. We present a
      case of a perforating pilomatricoma presenting as a cutaneous horn in an 11 year
      old girl. 

PMID- 24746309
TI  - An atlas of the morphological manifestations of hidradenitis suppurativa.
AB  - This article is dermatological atlas of the morphologic presentations of
      Hidradenitis Suppurativa (HS). It includes: superficial abscesses (boils,
      furnucles, carbuncles), abscesses that are subcutaneous and suprafascial,
      pyogenic granulomas, cysts, painful erythematous papules and plaques,
      folliculitis, open ulcerations, chronic sinuses, fistulas, sinus tracts, scrotal
      and genital lyphedema, dermal contractures, keloids (some that are still pitted
      with follicular ostia), scarring, skin tags, fibrosis, anal fissures, fistulas
      (i.e. circinate, linear, arcuate), scarring folliculitis of the buttocks (from
      mild to cigarette-like scarring), condyloma like lesions in intertrigous areas,
      fishmouth scars, acne inversa, honey-comb scarring, cribiform scarring, tombstone
      comedones, and morphia-like plaques. HS can co-exist with other follicular
      diseases such as pilonidal cysts, dissecting cellulitis, acne conglobata,
      pyoderma gangrenosum, and acanthosis nigricans. In sum, the variety of
      presentations of HS as shown by these images supports the supposition that HS is
      a reaction pattern.HS is a follicular based diseased and its manifestations
      involve a multitude of follicular pathologies [1,2]. It is also known as acne
      inversa (AI) because of one manifestation that involves the formation of open
      comedones on areas besides the face. It is as yet unclear why HS is so protean in
      its manifestations. HS severity is assessed using the Hurley Staging System
      (Table 1). It also remains unclear why hidradentitis may remain limited to Hurley
      Stage 1, evolve to the more confluent (Hurley Stage 2), or progress even further
      to the fully confluent (Hurley Stage 3).In addition, HS can be associated with
      other follicular based diseases such as pilonidal cysts (PCs) of the sacrum and
      buttocks, dissecting cellulitis (DC), and acne conglobata (AC), which usually
      involves the face, chest, When HS occurs with PCs, DC, and/or AC it is referred
      to as the follicular occlusion triad or tetrad [2]. HS can more rarely be
      associated with pyoderma gagrenosum (PG) or Crohn disease (CD), other
      inflammatory diseases of the skin that are not follicular. The reason for this is
      unclear [2]. What AC, DC, HS, CD, and PG share is that they occur in bacterially
      rich environments. HS probably occurs with acanthosis nigricans because many HS
      patients are obese [2]. This concurrence seems under reported. 

PMID- 24746310
TI  - Successful treatment of pityriasis rubra pilaris with adalimumab - case report.
AB  - Pityriasis Rubra Pilaris (PRP) is an uncommon skin disorder characterized by
      follicular keratosis, palmoplantar keratoderma, and erythroderma. The traditional
      preferred treatment is oral retinoids, but over the last decade, biologic therapy
      with anti-TNF agents has been used with success. We report the case of a 51 year-
      old man with a clinical and histopathological diagnosis of PRP. He underwent
      therapy with adalimumab and showed clearance of skin lesions within the fourth
      week of treatment. 

PMID- 24746311
TI  - [A case of lichenoid sarcoidosis with characteristic clinical and
      histopathological findings].
AB  - Sarcoidosis is a multisystem inflammatory disease characterized by the formation
      of noncaseating granulomas in various organs and tissues. The majority of
      patients with systemic sarcoidosis will present with lung and lymph node
      involvement. In addition, 20% have skin involvement that may be the only
      manifestation of the disease or may be an important prognostic marker for
      involvement of other organs. There are multiple forms of presentation of
      cutaneous sarcoidosis, which may be a true challenge.We report a patient with a
      one month history of an eruption of skin colored papules. Some were grouped in a
      symmetrical distribution on the trunk, inner arms, and lumbar region. Pathologic
      examination revealed an infiltrate in the papillary dermis showing a band of
      noncaseating granulomas along with disruption of the basal lamina and lichenoid
      changes. The clinicopathological correlation confirmed the diagnosis of lichenoid
      sarcoidosis. We consider our case interesting owing to the clinical presentation
      and the lichenoid distribution of granulomas. 

PMID- 24746312
TI  - Erythema nodosum - a review of an uncommon panniculitis.
AB  - Panniculitis, inflammation of the subcutaneous fat, is a relatively uncommon
      condition that usually presents with inflammatory nodules or plaques. Erythema
      nodosum (EN) is clinically the most frequent form of panniculitis and is
      considered a reactive process that may be triggered by a wide variety of stimuli.
      Whilst up to 55% of EN is considered idiopathic, the most common causes include
      infections, drugs, systemic illnesses such as sarcoidosis and inflammatory bowel
      disease, pregnancy, and malignancy. EN typically presents in the teens and 20s,
      and is seen more commonly in females. It is often preceded by a non-specific
      prodrome of one to three weeks, which may include fever, malaise, and symptoms of
      an upper respiratory tract infection. Cutaneous lesions then follow, typically
      localized on the extensor aspect of the limbs. The lesions are painful rounded or
      oval, slightly raised, non-ulcerative red nodules. The exact pathogenesis of EN
      is not understood, although is thought to result from deposition of immune
      complexes in the venules of the septae in subcutaneous fat, causing a
      neutrophilic panniculitis. The classical histopathological picture is of a septal
      panniculitis without vasculitis. However, the pathological features vary with the
      chronology of the lesions. Even without specific therapy for a causative
      condition, EN typically resolves without treatment. Therefore, symptomatic
      support is adequate for the majority of patients. 

PMID- 24746313
TI  - [Malignant acanthosis nigricans: report of a case].
AB  - The authors present a case of a 44-year-old patient with a disseminated
      dermatosis diagnosed as acanthosis nigricans. The patient was a smoker and
      investigation of the cause of her skin lesions resulted in discovery of an
      asymptomatic metastatic carcinoma in the laryngopharanx, probably of pulmonary
      origin.

PMID- 24746314
TI  - Stereoselectivity of the Honda-Reformatsky reaction in reactions with ethyl
      bromodifluoroacetate with alpha-oxygenated sulfinylimines.
AB  - The Reformatsky reaction of ethyl bromodifluoroacetate to alpha-oxygenated
      sulfinylimines is described. Using Honda-Reformatsky conditions, the reaction
      proceeds with double diastereodifferentiation, with the configuration of the
      sulfinyl group determining the stereochemical course of the reaction. Excellent
      diastereoselectivities (>94:6) are obtained for the matched cases. In contrast,
      reaction with sulfinylimines derived from unsubstituted alkanals proceeded with
      virtually no diastereoselectivity. 

PMID- 24746315
TI  - Locally ablative therapies for primary and metastatic liver cancer.
AB  - Locally ablative therapies have an increasing role in the effective
      multidisciplinary approach towards the treatment of both primary and metastatic
      liver tumors. In patients who are not considered surgical candidates and have low
      volume disease, these therapies have now become established into consensus
      practice guidelines. A large range of therapeutic options exist including
      percutaneous ethanol injection (PEI), radiofrequency ablation (RFA), microwave
      ablation (MWA), cryoablation, percutaneous laser ablation (PLA), irreversible
      electroporation (IRE), stereotactic body radiation therapy (SBRT) and high
      intensity focused ultrasound (HIFU); each having benefits and drawbacks. The
      greatest body of evidence supporting clinical utility in the liver currently
      exists for RFA, with PEI having fallen out of favor. MWA, IRE, SBRT and HIFU are
      relatively nascent technologies, and outcomes data supporting their use is
      promising. Future directions of ablative therapies include tandem approaches to
      improve efficacy in the treatment of liver tumors. 

PMID- 24746316
TI  - Comprehensive study of the chelation and coacervation of alkaline earth metals in
      the presence of sodium polyphosphate solution.
AB  - The effect of chelation of three alkaline earth metals (Ca, Sr, and Ba) by
      polyphosphates on the pH and viscosity of the solution is examined and correlated
      to the phosphate glass properties. Also, the impact of the polyphosphate average
      degree of polymerization (D(p)) as well as the type and amount of chelated
      divalent cation on the degradation rate of the chains is studied. Subsequently,
      the number of divalent cations required for polyphosphate chain agglomeration to
      form a coacervate, and the resulting composition of these coacervates, was
      investigated. A decrease in polyphosphate solution pH during chelation was
      routinely obtained, with a sudden shift in the rate of pH drop occurring around a
      divalent cation/phosphorus molar ratio of 0.18. Longer chains or cations with a
      smaller ionic radius accelerated the rate of D(p) reduction. The number of
      divalent cations required for coacervation depends on different variables such as
      the polyphosphate concentration, the D(p), and the type of divalent cation. The
      formed coacervate retains the D(p) of polyphosphate originally used for
      coacervation, and the resulting Ca/P molar ratio depends largely on the amount of
      calcium being used during coacervation. Overall, this article helps one to
      understand the coacervation of polyphosphates in order to exploit their potential
      as a biomaterial.

PMID- 24746327
TI  - Mini-invasive boomerang-plasty for esthetic restoration of lower third face
      aging.
AB  - INTRODUCTION: There is an increased demand to improve facial appearance and
      preserve a youthful appearance for as long as possible. Minimally invasive facial
      procedures have boomed among young patients with less evidence of scars, low
      risk, and rapid recovery being some of the attractions. Some patients are even
      only interested in the treatment of specific units of the face. We present an
      alternative technique to treat jowls through truly limited incisions. MATERIAL
      AND METHODS: The surgical protocol included a complete medical history, analysis
      of the degree of prominence of jowls, and development of a surgical plan. We
      obtained pre- and postoperative medium and long-term photographs and evaluated
      the results. The procedure is complemented with neck liposuction and
      platysmoplasty. RESULTS: In general, edema and ecchymosis disappeared within 2
      weeks. The recovery period was 2 to 3 weeks. The pre- and retroauricular scars
      over time were nearly imperceptible. Permanence of the results has been
      demonstrated in a follow-up period of 4 years. CONCLUSIONS: Our philosophical
      concept lies in the preventive benefit because it is mostly performed in
      relatively young patients. Boomerang-plasty anatomically restores the mandibular
      contour from the angle to the chin by eliminating jowls and establishes an
      esthetically harmonious visual difference between the face and neck. It is a
      simple procedure with highly satisfactory and stable effects.

PMID- 24746328
TI  - Clinical indicators that predict the presence of moderate to severe obstructive
      sleep apnea after adenotonsillectomy in children.
AB  - OBJECTIVE: To determine if clinical indicators can predict the presence of
      moderate to severe Obstructive Sleep Apnea (OSA) after Adenotonsillectomy (T&A)
      in children. STUDY DESIGN: Retrospective study. SETTING: Urban Tertiary Care
      Pediatric Hospital. METHODS: Parents of children (<18 yrs.) with OSA completed a
      55-item questionnaire based on their child's symptoms at the time of preoperative
      polysomnography and then again at the follow up polysomnography completed 3 to 6
      months after T&A. MAIN OUTCOME MEASURES: 55 item questionnaire, polysomnography
      variables. RESULTS: 97 children were included (59 Male and 38 Female). The mean
      preoperative apnea hypopnea index (AHI) was 30.5+/-31.6/h and the mean
      postoperative AHI was 4.4+/-6.0/h. After T&A, all 97 children had reduction in
      AHI, and 35 (36.1%) no longer had OSA (AHI<1/h). The total symptom scores
      decreased from 15.8+/-9.4 to 11.3+/-8.7 after T&A (p<.0001). Fourteen symptoms
      highly predictive of moderate to severe OSA were identified in the univariate
      analysis (p<0.1). Using a cut-point of 4, this 14-item subscale illustrated an
      overall predictability of 72.2% (73.7% sensitivity and 70.0% specificity) for
      identifying children with moderate to severe OSA. CONCLUSION: A cluster of 14
      clinical sleep symptoms are highly predictive of moderate to severe OSA and can
      serve as clinical predictor for the presence of moderate to severe OSA after T&A.

PMID- 24746329
TI  - Hearing restoration in NF2 patients and patients with vestibular schwannoma in
      the only hearing ear: report of two cases.
AB  - OBJECTIVE: To explore audiologic outcome of auditory brain stem implantation
      (ABI) and cochlear implantation (CI) in NF2 patients and patients with vestibular
      schwannoma (VS) in the only hearing ear. PATIENTS AND METHODS: Study includes
      retrospective analysis of 2 cases. One is totally deaf patient due to NF2, and
      the other one is totally deaf due to VS development in only hearing ear. Tumor
      was removed by retrosigmoid approach in NF2 patient and ABI was performed
      simultaneously. For the VS in only hearing ear case, tumor was removed by
      translabyrinthine approach and CI was performed simultaneously. RESULTS: ABI
      patient showed quite well outcome during the 15 months of follow-up. She has 25
      dB hearing threshold at speaking frequencies. She developed open set speech
      discrimination with 87.5% word discrimination score, and 70% sentence
      discrimination score. She uses device daily manner, she can use telephone. For CI
      patient, outcome is not perfect but satisfactory. She couldn't develop open set
      speech discrimination during the 18 months of follow-up. She has 67% the
      disyllabic words recognition score (close set). She is daily user of device. CI
      improves quite well lip reading. CONCLUSION: ABI and CI are the two options to
      restore hearing in VS caused deafness. We advocate giving every effort to
      preserve cochlear nerve during the VS resection and place CI simultaneously.
      However if it is not possible to preserve cochlear nerve during surgery, ABI is
      also a good alternative for hearing restoration.

PMID- 24746330
TI  - Early life stress: nature and nurture.

PMID- 24746333
TI  - Adaptive leadership: reacting to mission-critical milestones.

PMID- 24746334
TI  - Cardiac output measurement by bioimpedance and noninvasive pulse contour analysis
      compared with the continuous pulmonary artery thermodilution technique.
AB  - OBJECTIVE: The aim of the present study was to compare 2 noninvasive cardiac
      output measurement methods with the continuous cardiac output thermodilution (CCO
      TD) method. DESIGN: A single-center prospective design. SETTING: A university
      hospital. PARTICIPANTS: Fifty-three consecutive patients scheduled for elective,
      non-emergent cardiac surgery. INTERVENTIONS: With each participant the cardiac
      output was measured using 3 methods: CCO-TD, the Endotracheal Cardiac Output
      Monitor (ECOM), and the Nexfin monitor. MEASUREMENTS AND MAIN RESULTS:
      Measurements were performed simultaneously at 7 time points: After induction,
      before cardiopulmonary bypass, after cardiopulmonary bypass, after protamine,
      after arrival in the intensive care unit, and before extubation on postoperative
      day 1. Statistical analysis was performed using Pearson's correlation, Bland
      Altman, percent error, and polar plots. Compared to CCO-TD, ECOM showed
      significant correlation of R0.619 with a bias of -0.13 L/min (95% confidence
      interval -2.19-1.93 L/min), a percent error of 40%, and trending ability of 87%
      and 97% within 0.5 L/min and 1.0 L/min, respectively. The Nexfin monitor showed
      significant correlation of R0.535 with a bias of-0.35 L/min (95% confidence
      interval-3.36-2.66 L/min), a percent error of 58% and trending ability of 84% and
      97% were within 0.5 L/min and 1.0 L/min limits of agreement. CONCLUSIONS: Neither
      the ECOM nor the Nexfin had the ability to replace the thermodilution-based
      continuous cardiac output monitor. The ECOM did not have acceptable accuracy or
      trending ability and only could be utilized for intubated patients. The Nexfin
      lacked reliability and trending ability. Also, the Nexfin did not provide
      consistent results.

PMID- 24746335
TI  - Plasma vasopressin levels in patients with right-sided heart dysfunction and
      chronic thromboembolic pulmonary hypertension (CTEPH).
AB  - OBJECTIVES: Patients with left-sided heart dysfunction and volume overload often
      have associated elevations in vasopressin from neuroendocrine activation. The
      authors investigated perioperative levels of vasopressin in patients with
      isolated right-sided heart dysfunction from chronic thromboembolic pulmonary
      hypertension. DESIGN: Prospective, observational study. SETTING: Single center,
      tertiary hospital. PARTICIPANTS: Patients with chronic thromboembolic pulmonary
      hypertension undergoing pulmonary thromboendarterectomy. INTERVENTIONS:
      Vasopressin levels were measured in 22 patients during the perioperative period.
      MEASUREMENTS AND MAIN RESULTS: Vasopressin was undetectable in 8/22 patients at
      baseline. As a group, vasopressin levels at baseline and after induction of
      anesthesia were 0.8 pg/mL (median; 0.5-1.5, interquartile range of 25% and 75%)
      and 0.7 pg/mL (median; 0.5-1.4, interquartile range of 25% and 75%),
      respectively. During cardiopulmonary bypass (CPB), vasopressin increased to 13.9
      pg/mL (median; 6.7-19.9, interquartile range of 25% and 75%). Vasopressin
      remained elevated after deep hypothermic circulatory arrest (DHCA) at 10.5 pg/mL
      (median; 6.5-19.9 interquartile range of 25% and 75%) and after CPB at 19.9 pg/mL
      (median; 11.1-19.9 interquartile range of 25% and 75%). CONCLUSIONS: Vasopressin
      levels in PTE patients are in the low-to-normal range at baseline and may be a
      clinically relevant issue in the hemodynamic management of PTE.

PMID- 24746336
TI  - Implementing goal-directed protocols reduces length of stay after cardiac
      surgery.
AB  - OBJECTIVE: To test the effect of a high reliability organization (HRO)
      intervention on patient lengths of stay in the CVICU and hospital. The authors
      proposed that (1) higher safety related evidence based protocol (SREBP) team
      compliance scores and (2) lower SREBP milestone scores are associated with
      shorter lengths of CVICU and hospital stay. DESIGN: A prospective, longitudinal
      observational evaluation was used to assess the effects of SREBP-focused rounding
      processes and a milestone-tracking tool. SETTING: United States, university
      academic medical center's 27-bed CVICU. PARTICIPANTS: Six hundred sixty-five
      adult cardiac surgery patients and the CVICU care team (100 registered nurses and
      16 clinical providers) participated. MEASUREMENTS AND MAIN RESULTS: Team
      compliance was the proportion of SREBP-related team behaviors exhibited during
      daily rounds. Patients' milestone scores were the cumulative difference between
      actual and expected times for 4 SREBP milestones over 48 hours. Milestones
      achieved earlier than expected indicated reduced complication risk, and
      milestones achieved later than expected indicated increased risk. As team
      compliance increased, CVICU length of stay decreased 0.66 (95% CI: -0.04 to 1.28;
      p = 0.08) days; hospital stay decreased 0.89 times (95% CI: 0.77-1.03; p =
      0.008). As the mean milestone scores increased from -7 to 12, length of ICU stay
      increased 2.63 (95% CI: 1.66-3.59; p<0.001) days; hospital length of stay
      increased 1.44 times (95% CI: 1.23-1.7; p = 0.05). CONCLUSIONS: A milestone
      driven pathway supported by team rounding was associated with decreased lengths
      of CVICU and hospital stay. However, tracking patient trajectories by milestones
      suggests a more complex relationship than anticipated and presents new
      opportunities for SREBP implementation and research.

PMID- 24746337
TI  - Left ventricular outflow tract obstruction: is it the valve or something else?

PMID- 24746338
TI  - New frontiers in aortic therapy: focus on deliberate hypotension during thoracic
      aortic endovascular interventions.

PMID- 24746339
TI  - Back propagation neural network modelling of biodegradation and fermentative
      biohydrogen production using distillery wastewater in a hybrid upflow anaerobic
      sludge blanket reactor.
AB  - In a hybrid upflow anaerobic sludge blanket (HUASB) reactor, biodegradation in
      association with biohydrogen production was studied using distillery wastewater
      as substrate. The experiments were carried out at ambient temperature (34+/-1
      degrees C) and acidophilic pH of 6.5 with constant hydraulic retention time (HRT)
      of 24h at various organic loading rates (OLRs) (1-10.2kgCODm(-3)d(-1)) in
      continuous mode. A maximum hydrogen production rate of 1300mLd(-1) was achieved.
      A back propagation neural network (BPNN) model with network topology of 4-20-1
      using Levenberg-Marquardt (LM) algorithm was developed and validated. A total of
      231 data points were studied to examine the performance of the HUASB reactor in
      acclimatisation and operation phase. The statistical qualities of BPNN models
      were significant due to the high correlation coefficient, R(2), and lower mean
      absolute error (MAE) between experimental and simulated data. From the results,
      it was concluded that BPNN modelling could be applied in HUASB reactor for
      predicting the biodegradation and biohydrogen production using distillery
      wastewater. 

PMID- 24746340
TI  - Alkaline-mechanical pretreatment process for enhanced anaerobic digestion of
      thickened waste activated sludge with a novel crushing device: Performance
      evaluation and economic analysis.
AB  - Although various pretreatments have been widely investigated to enhance the
      anaerobic digestion (AD) of waste activated sludge (WAS), economic feasibility
      issues have limited real-world applications. The authors examined the performance
      and economic analysis of an alkaline-mechanical process with a novel mechanical
      crushing device for thickened WAS pretreatment. The pretreatment at 40gTS/L, pH
      13, and 90min reaction time achieved 64% of solubilization efficiency and 8.3
      times higher CH4 yield than the control. In addition, a synergistic CH4 yield
      enhancement was observed when the pretreated and raw WAS were used together as
      feedstock, and the greatest synergy was observed at a volumetric mixture ratio of
      50:50. Economic estimates indicate that up to 22% of WAS treatment costs would be
      saved by the installation of the suggested process. The experimental results
      clearly indicate that the alkaline-mechanical process would be highly effective
      and economically feasible for the AD of thickened WAS. 

PMID- 24746341
TI  - Spiropyran-modified gold nanoparticles: reversible size control of aggregates by
      UV and visible light irradiations.
AB  - UV or visible light irradiation of gold nanoparticles (AuNPs) modified with a
      thiol-terminated spiropyran dye promotes reversible aggregation or dispersion of
      AuNPs. This is facilitated by the electrostatic repulsion/attraction between the
      AuNPs controlled by the ring-opening/closing photoisomerization of the surface
      dyes. This photochemical method successfully produces aggregates of AuNPs with
      tunable sizes (20-340 nm) and narrow size distributions (standard deviation <34%)
      in a reversible manner. In addition, the formed aggregates, even when left in the
      dark condition, scarcely change their sizes because the stacking interaction
      between the ring-opened forms of surface dyes suppresses thermal reverse
      isomerization and maintains the attractive force between the AuNPs. 

PMID- 24746343
TI  - [Anticoagulant therapy clinic: moving towards Advanced Nursing Practice].
AB  - There is currently around one million people receiving oral anticoagulants in
      Spain. The drug most used is acenocoumarol, which requires coagulation monitoring
      to ensure that the patient is within its normal therapeutic range. Patients
      usually start this treatment in a hospital clinic and, when they are stabilised,
      they are referred to primary care, where they are followed-up by their community
      nurses. The usual practice is that nurses are responsible for changes in the dose
      when the patients are outside the range. This practice is not performed by
      hospital nurses, despite having sufficient experience and knowledge to adequately
      manage these types of patients. An Advanced Nursing Practice model has been
      introduced into the Haematology management unit of the Hospital Universitario
      Virgen de la Victoria, Malaga. This involves various aspects of attention and
      care of patients on anticoagulant therapy, and includes adjusting the doses of
      their treatment following a catalogue of therapeutic and diagnostic ranges. 

PMID- 24746342
TI  - Molecular and clinical epidemiology of norovirus outbreaks in Spain during the
      emergence of GII.4 2012 variant.
AB  - BACKGROUND: Norovirus (NoV) is the most common cause of acute nonbacterial
      gastroenteritis outbreaks worldwide, but the impact of NoV infections in Spain
      remains underestimated. OBJECTIVES: This study aimed to determine the prevalence
      and genetic diversity of NoVs causing outbreaks of acute gastroenteritis in
      Northeastern Spain (Catalonia) during 2010-2012, and to compare clinical features
      and levels of viral shedding of the most prevalent GII.4 2012 variant with its
      predecessor. STUDY DESIGN: NoVs were screened and genotyped in stools from
      gastroenteritis outbreaks. Genetic diversity over a region covering 50% of VP1,
      and viral loads were analyzed in stools belonging to GII.4 2009 and 2012
      variants. RESULTS: More than 50% of outbreaks were caused by genotype GII.4,
      although outbreaks caused by multiple strains, GII.6 and GII.1 were also
      prevalent. During 2012, GII.4 2012 strains clearly replaced GII.4 2009 strains.
      The first 2012 strain was detected in February 2011, representing the earliest
      isolate reported worldwide. Epidemiological features of GII.4 2012 and GII.4 2009
      outbreaks were comparable, as well as levels of viral shedding in stools.
      Finally, analysis of the capsid gene showed a higher amino acid variability and
      diversification in GII.4 2012, affecting sites located at the P2 domain, but also
      in the shell domain. CONCLUSIONS: Clinical features of outbreaks caused by
      different genotypes circulating in Spain, including outbreaks caused by GII.4
      2012 and GII.4 2009 strains, were comparable. Although shed at similar levels
      than GII.4 2009 strains, GII.4 2012 strains have clearly replaced the previous
      predominant strain.

PMID- 24746344
TI  - Trisubstituted 2-trifluoromethyl pyrrolidines via catalytic asymmetric Michael
      addition/reductive cyclization.
AB  - The stereoselective synthesis of trisubstituted 2-trifluoromethyl pyrrolidines by
      asymmetric Michael addition/hydrogenative cyclization is described. The direct
      organocatalytic addition of 1,1,1-trifluoromethylketones to nitroolefins proceeds
      under mild reaction conditions and low catalyst loadings to provide Michael
      adducts in high yield with excellent diastereo- and enantioselectivity. Catalytic
      hydrogenation of the Michael adducts stereoselectively generates 2
      trifluoromethylated pyrrolidines bearing three contiguous stereocenters. A
      stereospecific route to epimeric 2-trifluoromethyl pyrrolidines from a common
      intermediate is described. 

PMID- 24746345
TI  - What are young adults smoking in their hookahs? A latent class analysis of
      substances smoked.
AB  - RATIONALE: Hookah smoking continues to be a popular form of tobacco use,
      especially among college students. Although hookahs are commonly used to smoke
      tobacco, anecdotal evidence suggests other substances, including herbal shisha,
      marijuana and hashish may be used. However, little is known about the variety of
      substances smoked in hookahs, or correlates associated with different substances
      smoked. METHODS: In fall 2010, 3447 students from 8 colleges in N.C. completed an
      online survey. RESULTS: 44% of students reported ever smoking tobacco from a
      hookah. Of those ever users, 90% reported smoking flavored tobacco in a hookah,
      45% marijuana, 37% herbal (non-tobacco) shisha, and 18% hashish. Latent class
      analysis revealed two distinct classes. The most prevalent class (77%) primarily
      smoked flavored tobacco, with minimal use of herbal shisha and marijuana and
      virtually no use of hashish. The second class (23%) primarily smoked marijuana,
      hashish and flavored tobacco with moderate use of herbal shisha. Logistic
      regression analysis adjusting for clustering within schools revealed that males,
      illicit drug users, daily, nondaily and former cigarette smokers and those whose
      mothers had higher levels of education were significantly more likely to be in
      the second class compared to the first. CONCLUSIONS: Rates of lifetime use of
      hookah were high in our sample of college students. While the majority of hookah
      users smoked tobacco in hookahs, they also smoked other substances, notably
      marijuana and herbal shisha. Prevention efforts should recognize that students
      are using hookahs to smoke a variety of substances.

PMID- 24746346
TI  - Cerebral venous thrombosis as a rare cause of subarachnoid hemorrhage: case
      report and literature review.
AB  - We report a 48-year-old woman presenting with subarachnoid hemorrhage (SAH) as
      the first manifestation of superior sagittal sinus thrombosis. In a literature
      review of 73 cases, SAH associated with cerebral venous thrombosis (CVT) was
      usually seen at the cerebral convexities. SAH was adjacent to thrombosed venous
      structures; therefore, the most possible explanation seems to be the rupture of
      cortical veins due to extension of thrombosis. Computed tomography (CT) was
      effective for diagnosis of CVT in only 32% of the cases. CVT should be considered
      when SAH is limited to cerebral convexities and magnetic resonance (MR) imaging
      with MR venography should be performed. 

PMID- 24746347
TI  - Kinetics of the gas-phase reactions of chlorine atoms with naphthalene,
      acenaphthene, and acenaphthylene.
AB  - Reactions of polycyclic aromatic hydrocarbons (PAHs) with chlorine atoms may
      occur in specific areas such as coastal regions and the marine boundary layer. In
      this work, rate constants for the gas-phase reactions of naphthalene,
      acenaphthene, and acenaphthylene with chlorine atoms have been measured using the
      relative rate technique. Experiments were performed at room temperature (293 +/-
      2 K) and atmospheric pressure in an atmospheric simulation chamber using a proton
      transfer reaction mass spectrometer (PTR-MS) to monitor the concentrations of
      PAHs and the reference compounds (acetone, methanol, 1,3,5-trimethylbenzene, and
      isoprene) as a function of time. The rate constants obtained in this work were
      (in units of cm(3) molecule(-1) s(-1)) (4.22 +/- 0.46) * 10(-12), (3.01 +/- 0.82)
      * 10(-10), and (4.69 +/- 0.82) * 10(-10) for naphthalene, acenaphthene, and
      acenaphthylene, respectively. These are the first measurements of the rate
      constants for gas-phase reactions of Cl atoms with acenaphthene and
      acenaphthylene. The rate constant determined in this study for the reaction of
      naphthalene with Cl atoms is not in agreement with the only other previously
      reported value in the literature. The results are used to assess the potential
      role of chlorine atom reactions in the atmospheric oxidation of PAHs. 

PMID- 24746348
TI  - Biosensors in forensic analysis. A review.
AB  - Forensic analysis is an important branch of modern Analytical Chemistry with many
      legal and socially relevant implications. Biosensors can play an important role
      as efficient tools in this field considering their well known advantages of
      sensitivity, selectivity, easy functioning, affordability and capability of
      miniaturization and automation. This article reviews the latest advances in the
      use of biosensors for forensic analysis. The different methodologies for the
      transduction of the produced biological events are considered and the
      applications to forensic toxicological analysis, classified by the nature of the
      target analytes, as well as those related with chemical and biological weapons
      critically commented. The article provides several Tables where the more relevant
      analytical characteristics of the selected reported methods are gathered. 

PMID- 24746349
TI  - Observation of a physical matrix effect during cold vapour generation measurement
      of mercury in emissions samples.
AB  - The observation of a physical matrix effect during the cold vapour generation
      atomic fluorescence measurement of mercury in emissions samples is reported. The
      effect is as a result of the different efficiencies of liberation of reduced
      mercury from solution as the matrix of the solution under test varies. The result
      of this is that peak area to peak height ratios decease as matrix concentration
      increases, passing through a minimum, before the ratio then increases as matrix
      concentration further increases. In the test matrices examined - acidified
      potassium dichromate and sodium chloride solutions - the possible biases caused
      by differences between the calibration standard matrix and the test sample matrix
      were as large as 2.8% (relative) representing peak area to peak height ratios for
      calibration standards and matrix samples of 45 and 43.75, respectively. For the
      system considered there is a good correlation between the density of the matrix
      and point of optimum liberation of dissolved mercury for both matrix types.
      Several methods employing matrix matching and mathematical correction to overcome
      the bias are presented and their relative merits discussed; the most promising
      being the use of peak area, rather than peak height, for quantification. 

PMID- 24746350
TI  - Electrochemical monitoring of citric acid production by Aspergillus niger.
AB  - Hybrid electronic tongue was developed for the monitoring of citric acid
      production by Aspergillus niger. The system based on various
      potentiometric/voltammetric sensors and appropriate chemometric techniques
      provided correct qualitative and quantitative classification of the samples
      collected during standard Aspergillus niger culture and culture infected with
      yeast. The performance of the proposed approach was compared with the monitoring
      of the fermentation process carried out using classical methods. The results
      obtained proved, that the designed hybrid electronic tongue was able to evaluate
      the progress and correctness of the fermentation process. 

PMID- 24746351
TI  - Simultaneous determination of ascorbic acid, dopamine and uric acid based on
      tryptophan functionalized graphene.
AB  - A new type of tryptophan-functionalized graphene nanocomposite (Trp-GR) was
      synthesized by utilizing a facile ultrasonic method via pi-pi conjugate action
      between graphene (GR) and tryptophan (Trp) molecule. The material as prepared had
      well dispersivity in water and better conductivity than pure GR. The surface
      morphology of Trp-GR was characterized by scanning electron microscopy (SEM),
      transmission electron microscopy (TEM) and Raman spectroscopy. The
      electrochemical behaviors of ascorbic acid (AA), dopamine (DA), and uric acid
      (UA) were investigated by cyclic voltammetry (CV) on the surface of Trp-GR. The
      separation of the oxidation peak potentials for AA-DA, DA-UA and UA-AA was about
      182 mV, 125 mV and 307 mV, which allowed simultaneously determining AA, DA, and
      UA. Differential pulse voltammetery (DPV) was used for the determination of AA,
      DA, and UA in their mixture. Under optimum conditions, the linear response ranges
      for the determination of AA, DA, and UA were 0.2-12.9 mM, 0.5-110 MUM, and 10
      1000 MUM, with the detection limits (S/N=3) of 10.09 MUM, 0.29 MUM and 1.24 MUM,
      respectively. Furthermore, the modified electrode was investigated for real
      sample analysis.

PMID- 24746352
TI  - Enrichment and desalting of tryptic protein digests and the protein depletion
      using boron nitride.
AB  - Sample preparation still remains a great challenge in modern bioanalysis and the
      interest in new efficient solid phase extraction (SPE) materials still remains
      high. In this work, hexagonal boron nitride (h-BN) is introduced as a new SPE
      material for the isolation and enrichment of peptides. The h-BN is isoelectronic
      and structurally similar to graphite. It has remarkable properties including good
      thermal conductivity, excellent thermal and chemical stability and a better
      oxidation resistance than graphite. BN attracts increasing interest because of
      its wide range of applicability. In the present work, the great potential of h
      BN, as a new SPE-material, on the enrichment, preconcentration and desalting of
      tryptic digest of model proteins is demonstrated. A special attention was
      dedicated to the efficient enrichment of hydrophilic phosphopeptides. Two elution
      protocols were developed for the enrichment of peptides compatible for subsequent
      MALDI-MS and ESI-MS analysis. In addition, the recoveries of 5 peptides and 3
      phosphopeptides with wide range of pI values utilizing h-BN materials with
      different surface areas were investigated. 84-106% recovery rate could be
      achieved using h-BN materials. The results were compared with those obtained
      using graphite and silica C18 under the same elution conditions, and lower
      recoveries were obtained. In addition, h-BN was found to have a capability of
      protein depletion, which is requisite for the peptide profiling. 

PMID- 24746353
TI  - Design, characterization and applications of new ionic liquid matrices for
      multifunctional analysis of biomolecules: a novel strategy for pathogenic
      bacteria biosensing.
AB  - The design, preparation and performance for novel UV-light absorbing (room
      temperature) ionic liquid matrices (UV-RTILMs) for matrix assisted laser
      desorption/ionization mass spectrometry (MALDI-MS) were reported. A series of UV
      RTILMs was prepared by ultrasonication of equimolar of acid (mefenamic acid) and
      bases (aniline (ANI), pyridine (Pyr), dimethyl aniline (DMANI) and 2-methyl
      picoline (2-P)). The UV-RTILMs have not only significant absorbance at the
      desired wavelength (337 nm of the N2 Laser), but also have available protons that
      can easily undergo proton transfer reactions to ionize the target molecules. The
      novel UV-RTILMs have the ability to ionize different and wide classes of
      compounds such as drugs, carbohydrate, and amino acids. The new UV-RTILMs series
      have been successfully and selectively applied for biosensing the lysates of
      pathogenic bacteria in the presence of the cell macromolecules. A new strategy
      for biosensing pathogens was presented via sensing the pathogens lysate in the
      cell suspension. The new materials can effectively detect the bacterial toxins
      without separation or any pretreatment. They offered excellent ionization of
      labile oligosaccharides with protonated peaks. They could significantly enhance
      the analyte signals, produce homogeneous spotting, reducing spot-to-spot
      variation, excellent vacuum stability, higher ion peak intensity, and wide
      application possibility. The physical parameters such as molar refractivity,
      molar volume, parachor, surface tension, density and polarizability were
      calculated and tabulated. The new UV-RTILMs could offer excellent reproducibility
      and great repeatability and they are promising matrices for wide applications on
      MALDI-MS.

PMID- 24746354
TI  - Self-assembling protein platform for direct quantification of circulating
      microRNAs in serum with total internal reflection fluorescence microscopy.
AB  - MicroRNA (miRNA) has recently emerged as a new and important class of cellular
      regulators. Strong evidences showed that aberrant expression of miRNA is
      associated with a broad spectrum of human diseases, such as cancer, diabetes,
      cardiovascular and psychological disorders. However, the short length and low
      abundance of miRNA place great challenges for conventional techniques in the
      miRNA quantification and expression profiling. Here, we report a direct, specific
      and highly sensitive yet simple detection assay for miRNA without sample
      amplification. A self-assembled protein nanofibril acted as an online pre
      concentrating sensor to detect the target miRNA. Locked nucleic acid (LNA) of
      complimentary sequence was served as the probe to capture the target miRNA
      analyte. The quantification was achieved by the fluorescence intensity measured
      with total internal reflection fluorescence microscopy. A detection limit of 1 pM
      was achieved with trace amount of sample consumption. This assay showed efficient
      single-base mismatch discrimination. The applicability of quantifying circulating
      mir-196a in both normal and cancer patient's serums was also demonstrated.

PMID- 24746355
TI  - Postoperative stability for surgery-first approach using intraoral vertical ramus
      osteotomy: 12 month follow-up.
AB  - The aim of this study was to evaluate the postoperative stability of the surgery
      first approach using intraoral vertical ramus osteotomy (IVRO). We
      retrospectively studied a sample derived from the patients who were treated by
      the surgery-first approach using a LeFort I osteotomy and IVRO for correction of
      class III dentofacial deformity from 2008 to 2012. Lateral cephalograms taken
      preoperatively and 2 days, 6 months, and 12 months postoperatively were traced,
      and the skeletal and dental variables at different time points were analysed. The
      study sample comprised 37 subjects, mean (SD) age 23 (4) years. The mean (SD)
      total duration of treatment including postoperative orthodontics was 14 (6)
      months, and surgical movement of the maxillary A point was 0.75 (1.3)mm
      anteriorly, and 0.21 (1.79)mm superiorly. The surgical change in the position of
      the maxillary first molar was 1.01 (1.57)mm superiorly. The mean (SD) movement of
      mandible was 11.15 (5.4)mm posteriorly at pogonion and 1.02 (1.79)mm inferiorly
      at menton. There were no significant change in maxillary skeletal variables
      during the first year postoperative period. The surgical relapse of mandible at
      pogonion was 0.63 (2.31) mm anteriorly (p=0.01), however, the relapse in superior
      direction at menton was 2.86 (1.39) mm with statistical significance (p=0.01).
      The total duration of orthodontic treatment with surgery-first was roughly 5
      months shorter than conventional preoperative and postoperative orthodontic
      treatment. The surgery-first approach using IVRO is effective and predictable,
      and shortens the overall duration of treatment. Anterior relapse of the mandible
      was less than 1mm, and increased superior relapse can be compensated for with
      appropriate preoperative planning to provide a reliable outcome. This study was
      limited to 12 months' follow-up, and a long term follow-up study is indicated. 

PMID- 24746356
TI  - Geochemical characteristics of phosphorus in surface sediments of two major
      Chinese mariculture areas: the Laizhou Bay and the coastal waters of the Zhangzi
      Island.
AB  - Phosphorus (P) in surface sediments of the Laizhou Bay (LB) and the coastal
      waters around the Zhangzi Island (ZI) was analyzed. Six forms of P were separated
      - exchangeable or loosely sorbed P (Ads-P), aluminum-bound P (Al-P), iron-bound P
      (Fe-P), authigenic apatite plus CaCO3-bound P plus biogenic apatite (Ca-P),
      detrital apatite plus other inorganic P (De-P) and organic P (OP). The average
      contents of P in the LB were in the order: De-P>OP>Ca-P>Fe-P>Ads-P>Al-P; in the
      ZI, the corresponding order was De-P>OP>Fe-P>Ca-P>Ads-P>Al-P. Due to the high
      nutrient loadings from the surrounding rivers, TP contents in sediments of the LB
      were higher than in those of the ZI. The potential bio-available P (Ads-P and OP)
      accounted for 14.7% and 24.2% of TP in sediments of the LB and the ZI,
      respectively. 

PMID- 24746357
TI  - Marine debris ingestion by coastal dolphins: what drives differences between
      sympatric species?
AB  - This study compared marine debris ingestion of the coastal dolphins Pontoporia
      blainvillei and Sotalia guianensis in a sympatric area in Atlantic Ocean. Among
      the 89 stomach contents samples of P. blainvillei, 14 (15.7%) contained marine
      debris. For S. guianensis, 77 stomach contents samples were analyzed and only one
      of which (1.30%) contained marine debris. The debris recovered was plastic
      material: nylon yarns and flexible plastics. Differences in feeding habits
      between the coastal dolphins were found to drive their differences regarding
      marine debris ingestion. The feeding activity of P. blainvillei is mainly near
      the sea bottom, which increases its chances of ingesting debris deposited on the
      seabed. In contrast, S. guianensis has a near-surface feeding habit. In the study
      area, the seabed is the main zone of accumulation of debris, and species with
      some degree of association with the sea bottom may be local bioindicators of
      marine debris pollution. 

PMID- 24746359
TI  - [Some considerations on the Kernohan-Woltman phenomenon].

PMID- 24746358
TI  - Association between in vitro susceptibility to natamycin and voriconazole and
      clinical outcomes in fungal keratitis.
AB  - PURPOSE: To assess the association between minimum inhibitory concentration (MIC)
      and clinical outcomes in a fungal keratitis clinical trial. DESIGN: Experimental
      study using data from a randomized comparative trial. PARTICIPANTS: Of the 323
      patients enrolled in the trial, we were able to obtain MIC values from 221
      patients with monocular fungal keratitis. METHODS: The Mycotic Ulcer Treatment
      Trial I was a randomized, double-masked clinical trial comparing clinical
      outcomes of monotherapy with topical natamycin versus voriconazole for the
      treatment of fungal keratitis. Speciation and determination of MIC to natamycin
      and voriconazole were performed according to Clinical and Laboratory Standards
      Institute guidelines. The relationship between MIC and clinical outcome was
      assessed. MAIN OUTCOME MEASURES: The primary outcome was 3-month best spectacle
      corrected visual acuity. Secondary outcomes included 3-month infiltrate or scar
      size; corneal perforation and/or therapeutic penetrating keratoplasty; and time
      to re-epithelialization. RESULTS: A 2-fold increase in MIC was associated with a
      larger 3-month infiltrate or scar size (0.21 mm; 95% confidence interval [CI],
      0.10-0.31; P < 0.001) and increased odds of perforation (odds ratio, 1.32; 95%
      CI, 1.04-1.69; P = 0.02). No correlation was found between MIC and 3-month visual
      acuity. For natamycin-treated cases, an association was found between higher
      natamycin MIC with larger 3-month infiltrate or scar size (0.29 mm; 95% CI, 0.15
      0.43; P < 0.001) and increased perforations (odds ratio, 2.41; 95% CI, 1.46-3.97;
      P < 0.001). Among voriconazole-treated cases, the voriconazole MIC did not
      correlate with any of the measured outcomes in the study. CONCLUSIONS: Decreased
      susceptibility to natamycin was associated with increased infiltrate or scar size
      and increased odds of perforation. There was no association between
      susceptibility to voriconazole and outcome.

PMID- 24746360
TI  - [Evaluation of postoperative myocardial injury by heart-type fatty acid-binding
      protein in off-pump coronary artery bypass grafting surgery].
AB  - BACKGROUND AND GOAL OF STUDY: Postoperative myocardial infarction is a serious
      and frequent complication of cardiac surgery. Nonetheless, diagnosis in this
      context it is occasionally challenging. We sought to evaluate the kinetics and
      diagnostic accuracy of the new biomarker " heart-type fatty acid-binding protein
      " (h-FABP) in the early detection of myocardial injury in patients undergoing off
      pump coronary artery bypass grafting, compared with classical biomarkers.
      MATERIALS AND METHODS: A prospective study was conducted on 17 consecutive
      patients who underwent off-pump coronary artery bypass grafting during a 2 month
      period. Blood samples were drawn for measurement of myocardial ischemic injury
      biomarkers (h-FABP, troponin, creatine kinase [CK] and CK-MB), at baseline (T1),
      immediate post-coronary artery bypass grafting (T2), on ICU admission (T3), and
      after 4 (T4), 8 (T5), 24 (T6) and 48 h (T7). Perioperative ischemic
      complications, defined according to electrocardiographic, echocardiographic and
      hemodynamic criteria, were recorded. RESULTS: Earlier biomarkers peak plasma
      values occurred at T4 with troponin (2.9 +/- 5.2 ng/mL), and at T5 with h-FABP
      (37.9 +/- 55.5 ng/mL). Maximum values of CK and CK-MB occurred later, both in T6
      (741 +/- 779 and 37 +/- 51 U/L, respectively). The optimized cut-off obtained for
      h-FABP was 19 ng/mL, providing a sensitivity and specificity of 77 and 75%,
      respectively, for diagnosis of perioperative ischemic injury, with an area under
      the ROC curve for h-FABP of 0.83 (95% CI 0.6-1.0) vs. 0.63 (95% CI 0.33-0.83) for
      troponin. This cut-off value for h-FABP is reached on average at T2 (mean value
      of h-FABP at T2: 18.9 +/- 21.5 ng/mL). CONCLUSION: This is the first study
      evaluating the kinetics of h-FABP biomarker in perioperative off-pump coronary
      artery bypass grafting, and the cut-off value established could help to extend
      earlier detection of myocardial ischemia in this context.

PMID- 24746361
TI  - SHOX2 is a direct miR-375 target and a novel epithelial-to-mesenchymal transition
      inducer in breast cancer cells.
AB  - MicroRNAs have added a new dimension to our understanding of tumorigenesis and
      associated processes like epithelial-to-mesenchymal transition (EMT). Here, we
      show that miR-375 is elevated in epithelial-like breast cancer cells, and ectopic
      miR-375 expression suppresses EMT in mesenchymal-like breast cancer cells. We
      identified short stature homeobox 2 (SHOX2) as a miR-375 target, and miR-375
      mediated suppression in EMT was reversed by forced SHOX2 expression. Ectopic
      SHOX2 expression can induce EMT in epithelial-like breast cancer cells, whereas
      SHOX2 knockdown diminishes EMT traits in mesenchymal-like breast cancer cells,
      demonstrating SHOX2 as an EMT inducer. We show that SHOX2 acts as a transcription
      factor to upregulate transforming growth factor beta receptor I (TbetaR-I)
      expression, and TbetaR-I inhibitor LY364947 abolishes EMT elicited by ectopic
      SHOX2 expression, suggesting that transforming growth factor beta signaling is
      essential for SHOX2-induced EMT. Manipulating SHOX2 abundance in breast cancer
      cells impact in vitro invasion and in vivo dissemination. Analysis of breast
      tumor microarray database revealed that high SHOX2 expression significantly
      correlates with poor patient survival. Our study supports a critical role of
      SHOX2 in breast tumorigenicity. 

PMID- 24746362
TI  - Novel alpha-synuclein mutation A53E associated with atypical multiple system
      atrophy and Parkinson's disease-type pathology.
AB  - We describe the clinical, neuropathological, and genetic features of a Finnish
      patient with a novel alpha-synuclein (SNCA) mutation A53E. The patient was
      clinically diagnosed with atypical Parkinson's disease (PD) with age of onset at
      36 years. In the neuropathological analysis performed at the age of 60 years,
      highly abundant SNCA pathology was observed throughout the brain and spinal cord
      showing features of multiple system atrophy and PD. Neuronal and glial (including
      oligodendroglial) SNCA inclusions and neurites were found to be particularly
      prominent in the putamen, caudatus, amygdala, temporal and insular cortices,
      gyrus cinguli, and hippocampus CA2-3 region. These areas as well as the
      substantia nigra and locus coeruleus showed neuronal loss and gliosis. We also
      found TDP-43 positive but mostly SNCA negative perinuclear inclusions in the
      dentate fascia of the hippocampus. The A53E mutation was found in 2 other
      relatives who had parkinsonism. Our results suggest that the novel SNCA A53E
      substitution is a causative mutation resulting clinically in parkinsonism and
      pathologically in severe multiple system atrophy- and PD-type phenotype.

PMID- 24746363
TI  - Altered arginine metabolism in Alzheimer's disease brains.
AB  - L-arginine is a semi-essential amino acid with a number of bioactive metabolites.
      Accumulating evidence suggests the implication of altered arginine metabolism in
      the pathogenesis of Alzheimer's disease (AD). The present study systematically
      compared the metabolic profile of L-arginine in the superior frontal gyrus,
      hippocampus, and cerebellum from AD (mean age 80 years) and normal (mean age 80
      or 60 years) cases. The activity and protein expression of nitric oxide synthase
      and arginase were altered with AD and age in a region-specific manner. There were
      also AD- and age-related changes in the tissue concentrations of L-arginine and
      its downstream metabolites (L-citrulline, L-ornithine, agmatine, putrescine,
      spermidine, spermine, glutamate, gamma-aminobutyric acid, and glutamine) in a
      metabolite- or region-specific manner. These findings demonstrate that arginine
      metabolism is dramatically altered in diverse regions of AD brains, thus meriting
      further investigation to understand its role in the pathogenesis and/or
      progression of the disease.

PMID- 24746364
TI  - APOE epsilon2 allele may decrease the age at onset in patients with
      spinocerebellar ataxia type 3 or Machado-Joseph disease from the Chinese Han
      population.
AB  - Polymorphism of the apolipoprotein E (APOE) gene has been defined as a modifying
      factor for age at onset (AO) in neurodegenerative disorders. The AO of
      spinocerebellar ataxia type 3 or Machado-Joseph disease (SCA3 or MJD) is
      inversely correlated with expanded CAG repeat lengths in the ATXN3 gene; however,
      AO is only partially explained by the expanded CAG repeats. We performed a case
      control study to explore whether APOE genotypes play a role in AO of SCA3 or MJD
      from the Chinese Han population. The APOE genotypes were analyzed in an
      independent cohort of 155 patients with SCA3 or MJD and 191 controls both from
      Mainland China. Our study demonstrated that SCA3 or MJD patients experienced an
      earlier onset if they were carriers of APOE epsilon2 allele, which decreased the
      AO by nearly 4 years. This study may also reconfirm the effect of the APOE gene
      on SCA3 or MJD patients from different races and indicated that certain APOE
      alleles might be genetic modifiers for AO in SCA3 or MJD.

PMID- 24746365
TI  - PDE9A inhibition rescues amyloid beta-induced deficits in synaptic plasticity and
      cognition.
AB  - The cyclic nucleotide cGMP is an important intracellular messenger for synaptic
      plasticity and memory function in rodents. Therefore, inhibition of cGMP
      degrading phosphodiesterases, like PDE9A, has gained interest as potential target
      for treatment of cognition deficits in indications like Alzheimer's disease (AD).
      In fact, PDE9A inhibition results in increased hippocampal long-term potentiation
      and exhibits procognitive effects in rodents. To date, however, no evidence has
      been published linking PDE9A inhibition to the pathologic hallmarks of AD such as
      amyloid beta (Abeta) deposition. Therefore, we investigated the role of PDE9A
      inhibition in an AD relevant context by testing its effects on Abeta-related
      deficits in synaptic plasticity and cognition. The PDE9A inhibitor BAY 73-6691
      was found to restore long-term potentiation impaired by Abeta42 oligomers.
      Furthermore, we demonstrated that BAY 73-6691 enhanced cGMP levels in the
      hippocampus of APP transgenic tg2576 mice and improved memory performance of
      these mice. Altogether, our results support the hypothesis that inhibition of
      PDE9A could be a beneficial approach for the treatment of memory impairment in AD
      patients.

PMID- 24746372
TI  - Adult smokers' responses to "corrective statements" regarding tobacco industry
      deception.
AB  - BACKGROUND: To inform consumers, U.S. Federal Courts have ordered the tobacco
      industry to disseminate "corrective statements" (CSs) about their deception
      regarding five topics: smoker health effects, nonsmoker health effects, cigarette
      addictiveness, design of cigarettes to increase addiction, and relative safety of
      light cigarettes. PURPOSE: To determine how smokers from diverse backgrounds
      respond to the final, court-mandated wording of these CSs. METHODS: Data were
      analyzed from an online consumer panel of 1,404 adult smokers who evaluated one
      of five CS topics (n=280-281) by reporting novelty, relevance, anger at the
      industry, and motivation to quit because of the CS. Logistic and linear
      regression models assessed main and interactive effects of race/ethnicity,
      gender, education, and CS topic on these responses. Data were collected in
      January 2013 and analyzed in March 2013. RESULTS: Thirty percent to 54% of
      participants reported that each CS provided novel information, and novelty was
      associated with greater relevance, anger at the industry, and motivation to quit
      because of the message. African Americans and Latinos were more likely than non
      Hispanic whites to report that CSs were novel, and they had stronger responses to
      CSs across all indicators. Compared to men, women reported that CSs were more
      relevant and motivated them to quit. CONCLUSIONS: This study suggests that
      smokers would value and respond to CSs, particularly smokers from groups that
      suffer from tobacco-related health disparities.

PMID- 24746373
TI  - Prevalence of psoriasis among adults in the U.S.: 2003-2006 and 2009-2010
      National Health and Nutrition Examination Surveys.
AB  - BACKGROUND: A 2010 CDC-sponsored consultation of psoriasis, psoriatic arthritis,
      and public health experts developed a public health agenda for psoriasis and
      psoriatic arthritis indicating that additional population-based research is
      needed to better characterize psoriasis in the population. PURPOSE: To better
      characterize the burden of psoriasis in the U.S. using recent population-based,
      cross-sectional data in this 2012 analysis. METHODS: A subset of 10,676 adults
      aged 20-59 years from the 2003-2006 and 2009-2010 National Health and Nutrition
      Examination Surveys was used to examine psoriasis prevalence, severity,
      disparities, health-related quality of life, and selected comorbidities. RESULTS:
      The overall prevalence of psoriasis was 3.1% (95% CI=2.6, 3.6); extrapolating to
      older adults suggests that 6.7 million adults aged >=20 years are affected.
      Psoriasis was significantly more prevalent among non-Hispanic whites than other
      race/ethnicity subgroups, as well as among those with arthritis. Approximately
      82% reported no/little or mild disease; the impact of psoriasis on daily life
      increased with disease severity (p=0.0001 for trend). Those with psoriasis
      reported significantly more frequent mental distress or mild to severe depression
      than those without psoriasis. Psoriasis was also significantly associated with
      obesity and former smoking status. CONCLUSIONS: Psoriasis is a large public
      health problem. Further characterizing psoriasis from a public health perspective
      will require better survey questions and inclusion of these questions in national
      surveys.

PMID- 24746374
TI  - Prospective associations between perceived barriers to condom: use and "perfect
      use".
AB  - BACKGROUND: Identifying malleable predictors of condom use in a clinic-based
      population may benefit efforts to prevent sexually transmitted infections (STIs).
      PURPOSE: To prospectively test associations between three measures (relational
      trust factors, fit and feel, and dislike of condom use) and perfect condom use in
      patients attending clinics diagnosing STIs. METHODS: A convenience sample was
      recruited from five clinics in three U.S. cities. Data were collected from
      December 2007 through April 2011. Daily electronic diaries were completed for up
      to 180 days. Occasions of penile-vaginal intercourse (PVI) involving condom use
      without any of four errors/problems were classified as "perfect use." Three
      subscales (relational-trust factors, fit and feel, and dislike of condom use)
      were developed from baseline data. Generalized estimating equations were used to
      account for non-independence of PVI events. RESULTS: Among 17,156 reported
      occasions of PVI, condoms were either not used or used with errors/problems in
      8,857 (51.6%) instances. The remaining 8,829 occasions (48.4%) involved perfect
      use. Relational-trust (p=0.054) and fit and feel (p=0.13) issues were not
      significantly associated with perfect use. Dislike of condom use (p=0.005) was
      significantly associated with perfect use (estimated OR=0.93, 95% CI=0.89, 0.98).
      Significant interactions with race, age, or gender were not observed.
      CONCLUSIONS: Clinic attendees may be more likely to use condoms perfectly if
      three perceptions are reduced in magnitude: I won't use condoms, condoms spoil
      the mood, and I get turned off when my partner suggests we use condoms. Findings
      support a paradigm shift in the way clinics promote condom use to patients.

PMID- 24746375
TI  - What's the healthiest day?: Circaseptan (weekly) rhythms in healthy
      considerations.
AB  - BACKGROUND: Biological clocks govern numerous aspects of human health, including
      weekly clocks-called circaseptan rhythms-that typically include early-week spikes
      for many illnesses. PURPOSE: To determine whether contemplations for healthy
      behaviors also follow circaseptan rhythms. METHODS: We assessed healthy
      contemplations by monitoring Google search queries (2005-2012) in the U.S. that
      included the word healthy and were Google classified as health-related (e.g.,
      healthy diet). A wavelet analysis was used in 2013 to isolate the circaseptan
      rhythm, with the resulting series compared by estimating ratios of relative query
      volume (healthy versus all queries) each day (e.g., (Monday
      Wednesday)/Wednesday). RESULTS: Healthy searches peaked on Monday and Tuesday,
      thereafter declining until rebounding modestly on Sunday. Monday and Tuesday were
      statistically indistinguishable (t=1.22, p=0.22), but their combined mean had 30%
      (99% CI=29, 32) more healthy queries than the combined mean for Wednesday-Sunday.
      Monday and Tuesday query volume was 3% (99% CI=2, 5) greater than Wednesday, 15%
      (99% CI=13, 17) greater than Thursday, 49% (99% CI=46, 52) greater than Friday,
      80% (99% CI=76, 84) greater than Saturday, and 29% (99% CI=27, 31) greater than
      Sunday. We explored media-based (priming) motivations for these patterns and they
      were consistently rejected. CONCLUSIONS: Just as many illnesses have a weekly
      clock, so do healthy considerations. Discovery of these rhythms opens the door
      for a new agenda in preventive medicine, including implications for hypothesis
      development, research strategies to further explore these rhythms, and
      interventions to exploit daily cycles in healthy considerations.

PMID- 24746377
TI  - 201st ENMC International Workshop: Autophagy in muscular dystrophies-
      translational approach, 1-3 November 2013, Bussum, The Netherlands.

PMID- 24746376
TI  - Smoking cessation and recidivism in the Women's Interagency Human
      Immunodeficiency Virus Study.
AB  - BACKGROUND: Smoking increases the risk of morbidity and mortality and is
      particularly harmful to HIV-infected people. PURPOSE: To explore smoking trends
      and longitudinal factors associated with smoking cessation and recidivism among
      participants in the Women's Interagency HIV Study. METHODS: From 1994 through
      2011, a total of 2,961 HIV-infected and 981 HIV-uninfected women were enrolled
      and underwent semi-annual interviews and specimen collection. Smoking prevalence
      was evaluated annually and risk factors associated with time to smoking cessation
      and recidivism were analyzed in 2013 using survival models. RESULTS: The annual
      cigarette smoking prevalence declined from 57% in 1995 to 39% in 2011 (p
      trend<0.0001). Among smokers, factors significantly associated with a longer time
      to smoking cessation included less education, alcohol use, having health
      insurance, >10-year smoking duration, self-reported poor health rating, and
      having hypertension. Pregnancy in the past 6 months was associated with a shorter
      time to cessation. Among HIV-infected women, additional risk factors for longer
      time to cessation included lower household income, use of crack/cocaine/heroin,
      CD4 cell count <=200, and highly active antiretroviral therapy (HAART) use.
      Predictors of smoking recidivism included marijuana use, enrollment in 1994-1996,
      and not living in one's own place. Among HIV-infected women, enrollment in 2001
      2002 and crack/cocaine/heroin use were associated with a shorter time to
      recidivism, whereas older age and HAART use were associated with a longer time to
      recidivism. CONCLUSIONS: Despite declining rates of cigarette smoking, integrated
      interventions are needed to help women with and at risk for HIV infection to quit
      smoking and sustain cessation.

PMID- 24746378
TI  - Can a surgeon predict the risk of postoperative hypoparathyroidism during thyroid
      surgery? A prospective study on self-assessment by experts.
AB  - BACKGROUND: Thyroid surgery can cause postoperative hypocalcemia (POH) and
      permanent hypoparathyroidism (PEH). Surgeons implicitly assess the risk and adapt
      their surgical strategy accordingly. METHODS: The outcome of this intraoperative
      decision-making process (the surgeons' ability to predict the risk of POH and PEH
      on a numerical rating scale and their actual incidence) was studied prospectively
      in 2,558 consecutive thyroid operations. RESULTS: POH and PEH occurred in 723 and
      64 patients, respectively. In multivariate analysis, the surgeons' risk
      assessment score was an independent predictive factor for both complications (P <
      .05). Surgeons' differed significantly (P = .015) in their rates of POH but not
      of PEH (P = .062). Six and 3 (of 9) surgeons correctly predicted an increased
      risk of PEH and POH (adjusted odds ratios 1.67 to 2.21 and 1.47 to 12.73),
      respectively. CONCLUSION: The risk for hypoparathyroidism can be estimated, but
      surgeons differ substantially in this ability and in the extent to which this
      implicit knowledge is translated into lower complication rates.

PMID- 24746379
TI  - Women's expectations and experiences of maternity care in NSW--what women
      highlight as most important.
AB  - BACKGROUND: Although surveys have identified that women are generally highly
      satisfied with maternity care provision, those aspects of care that women
      highlight as most important for achieving satisfaction and a satisfactory
      maternity care experience have not been reported. The aim of this study was to
      investigate how women understand and experience their maternity care and to
      report which aspects of care women highlight as most important. METHODS: This
      large qualitative study explored women's expectations and experiences of
      maternity care provision. In-depth semi-structured interviews were conducted with
      53 women experiencing maternity care in a range of tertiary, regional, rural,
      remote hospitals and midwife-led practices in the state of New South Wales,
      Australia during 2011-2012. Included in the interview schedule was the question
      'What 3 aspects would you see as most important for delivery of maternity care?'
      Descriptive analyses of entire transcripts and responses to the question on most
      important aspects of care were undertaken. RESULTS: Descriptive analyses of
      women's responses identified 5 important aspects of care: woman-focused care,
      staff qualities, systems and facilities, family-focused care and continuity of
      care/information. First-time mothers were more likely to identify woman-focused
      care, staff qualities and continuity of care/information as important aspects
      than multiparous mothers. Urban and regional mothers highlighted staff qualities
      as having greater importance for satisfaction with their care while rural and
      particularly remote women nominated systems and facilities as important.
      CONCLUSIONS: Our study showed that women from a range of settings are more
      concerned with staff and relational issues than facilities. Differences in
      perceptions among primiparous versus multiparous women, at different stages of
      pregnancy and among women from rural and remote compared to urban settings
      highlight the need to include women with a diversity of experience when trying to
      understand the aspects of maternity care most important to women.

PMID- 24746380
TI  - [Normal abdominal ultrasound anatomy. Examination procedure].
AB  - To carry out an abdominal ultrasound examination with the highest degree of
      accuracy and thoroughness, it is essential to have a good knowledge of the
      anatomy and the normal measurements of the different organs. In this way, we can
      determine their normal condition and identify the pathology and its location more
      easily. It is very important to adopt a correct examination procedure,
      systematically sweeping the scan in the same direction and not leaving any organ
      unexamined. We suggest a procedure consisting of longitudinal, cross-sectional
      and oblique scans to view all the abdominal organs, starting the examination in
      the epigastric region, scanning first the right upper quadrant, then the left
      upper quadrant, both iliac fossa, and lastly the hypogastric region. 

PMID- 24746381
TI  - Intraindividual comparison of changes in corneal biomechanical parameters after
      femtosecond lenticule extraction and small-incision lenticule extraction.
AB  - PURPOSE: To compare the biomechanical changes after femtosecond lenticule
      extraction and small-incision lenticule extraction for myopia. SETTING:
      Department of Ophthalmology, Kitasato University, Kanagawa, Japan. DESIGN:
      Comparative case series. METHODS: In eyes of consecutive patients, femtosecond
      lenticule extraction was performed in 1 eye and small-incision lenticule
      extraction in the other eye (both Visumax laser) by random assignment. Corneal
      hysteresis (CH) and the corneal resistance factor (CRF) were quantitatively
      assessed using a dynamic bidirectional applanation device (Ocular Response
      Analyzer) in relation to the amount of myopic correction preoperatively and 1
      week and 1 and 3 months postoperatively. RESULTS: This study comprised 48 eyes
      (24 patients). The decrease in CH and the CRF was statistically significant 1
      week after both lenticule extraction procedures; however, the changes
      subsequently stabilized with no further deterioration (P<.001). There were no
      statistically significant differences between the biomechanical changes in the 2
      procedures at any time; however, a significant correlation was found between the
      changes and the myopic correction 3 months after femtosecond lenticule extraction
      (r = 0.41, P=.046, CH; r = 0.41, P=.045, CRF) and after small-incision lenticule
      extraction (r = 0.62, P=.001, CH; r = 0.67, P<.001, CRF). CONCLUSIONS: The
      greatest changes in biomechanical parameters occurred within 1 week after
      femtosecond lenticule extraction and small-incision lenticule extraction; the
      changes were then nearly stable in relation to the amount of myopic correction.
      This suggests that the presence or absence of flap lifting does not significantly
      affect biomechanical parameters. FINANCIAL DISCLOSURE: No author has a financial
      or proprietary interest in any material or method mentioned.

PMID- 24746382
TI  - The importance of evolution in the development and course of rheumatoid
      arthritis.
AB  - Rheumatoid arthritis (RA) is a complex autoimmune disease of recent evolutionary
      origin. Genetic drift determines diverse polymorphisms implicated in the
      susceptibility to RA including the major histocompatibility complex (MHC) class
      II genes in the so-called shared epitope. These genes originated after the
      divergence between Homo and Pan from their common ancestry Ardipithecus ramidus
      about 5 million years ago. Natural selection determined the particular changes in
      the legs (bipedal position), hands, neck, brain and eusociality in humans which
      influence the clinical presentation of RA. In this article, we hypothesized that
      the origin and course of RA may be explainable in the light of evolution. 

PMID- 24746383
TI  - GLP-1 receptor agonists and the risk of colorectal cancer.

PMID- 24746384
TI  - Assessment of three-dimensional nasolabial response to Le Fort I advancement.
AB  - BACKGROUND: Le Fort I advancement induces soft tissue changes to the nasolabial
      region. The correlation of sagittal skeletal movement to soft tissue alteration
      has been studied using 2D methods. However, the influence of maxillary
      advancement has not been adequately assessed using three-dimensional means. The
      purpose of this study is to analyze nasolabial changes following Le Fort I
      advancement using 3D photometric measurements. METHODS: Patient demographic
      information and their amount of advancement were tabulated. Pre- and
      postoperative 3D photographs (3D VECTRA photosystem, Canfield, Fairfield, NJ)
      were recorded. Nasolabial anthropometric measurements were performed using the
      corresponding 3D post-processing software (Mirror). Six month minimum follow-up
      elapsed before final evaluation. RESULTS: Forty-four 3D photo data sets were
      included. Mean maxillary advancement was 5.5 (+/-1.9) mm. Male/female ratio was
      0.7 with a mean age of 16.7 years. Significant increases (p < 0.0001) were seen
      in the alar base, alar widths, nostril width, and in the soft triangle and
      lateral alar angles. Significant decreases (p < 0.0001) were noted in the
      nasofrontal angle and in nostril height. A significant (p < 0.05) increase of the
      nasal tip, columella and upper lip projection was seen. Philtral height showed no
      significant changes (p > 0.05) after maxillary advancement. No significant
      correlation (p > 0.05) between the degree of soft tissue changes and the amount
      of maxillary advancement was found. CONCLUSION: Le Fort I advancement
      significantly impacts the nasolabial soft tissue envelope. The 3D soft tissue
      changes are predictable and similar for any advancement up to 10 mm.

PMID- 24746385
TI  - Posterior interosseous artery perforator-free flap: treating intermediate-size
      hand and foot defects.
AB  - INTRODUCTION: Ambiguous defects on the hand and foot, especially on the fingers
      and toes, are still challenging to treat despite achievements in reconstruction.
      AIM: The purpose of this study was to evaluate the use of the posterior
      interosseous artery perforator flap for resurfacing intermediate-sized defects
      and provide adequate coverage over tendons and bones. METHOD: Between October
      2008 and March 2013, a total of 19 patients with soft-tissue defects on the hand
      or foot were treated. Flap elevation, anatomy, and clinical progress were
      evaluated. RESULT: All flaps survived and covered the defects, which ranged in
      area from 12 to 45 cm(2). The freestyle approach was used to harvest the flaps.
      The average length of the pedicle was 2.5 cm, and the pedicle was harvested
      without affecting the source vessel. The average diameter of the artery was 0.8
      mm, and the average thickness of the flap was 3.5 mm. Anastomosis was performed
      either end-to-end on the perforator, or end-to-side on deep vessels. No
      subsequent thinning or surgical flap correction was necessary. Ambulation was
      allowed at 3 days postsurgery. The donor site was closed primarily to leave an
      acceptable donor site. DISCUSSION: A posterior interosseous artery perforator
      free flap is a suitable choice for intermediate-size defects that are too large
      to cover using a local flap or too small for a first-line perforator flap. Up to
      45 cm(2) of adequate coverage can be provided using a thin posterior interosseous
      artery perforator-free flap that does not require additional debulking. The
      disadvantages of a short pedicle can be overcome using perforator-to-perforator
      supermicrosurgery.

PMID- 24746386
TI  - Primary open-angle glaucoma in a population associated with high prevalence of
      primary angle-closure glaucoma: the Kumejima Study.
AB  - PURPOSE: To evaluate the prevalence of and risk factors for primary open-angle
      glaucoma (POAG) in a rural population of southwestern Japan. DESIGN: Population
      based cross-sectional study. PARTICIPANTS: All residents 40 years of age and
      older in Kumejima, Okinawa, Japan. METHODS: Of the eligible 4632 residents 40
      years of age and older, 3762 subjects (participant rate, 81.2%) underwent
      screening examinations, including visual acuity (VA) measurement, slit-lamp
      examination, Goldmann applanation tonometry, gonioscopy, undilated stereoscopic
      fundus photographs, autorefractometry, noncontact specular microscopy,
      pachymetry, and visual field (VF) testing using frequency-doubling technology. If
      glaucoma or other related ocular disorders were suspected, subjects were referred
      for definitive examinations including VF testing with the Humphrey Field
      Analyzer. The diagnosis of POAG was based on the criteria of the International
      Society for Geographical and Epidemiological Ophthalmology. MAIN OUTCOME
      MEASURES: Prevalence and risk factors of POAG. RESULTS: The prevalence of POAG
      was 4.0% (95% confidence interval [CI], 3.4%-4.7%); 82% of patients had an
      intraocular pressure (IOP) less than 22 mmHg, resulting in a prevalence of 3.3%
      (95% CI, 2.8%-3.9%). Because of POAG, 3 subjects had a VA worse than 20/400 in
      only 1 eye, and 1 subject had VA loss of worse than 20/400 bilaterally. The
      average IOP values (mean +/- standard deviation) were 14.9 +/- 3.2 and 14.6 +/-
      3.3 mmHg in the right and left eyes, respectively; the IOP values were higher in
      patients with POAG (15.4 +/- 3.3 and 15.2 +/- 3.3 mmHg, respectively) than in
      subjects without glaucoma (14.8 +/- 3.1 and 14.4 +/- 3.1 mmHg, respectively;
      P<0.045, Student t test). Multivariate analysis showed that male gender (P =
      0.003), older age (P<0.001), higher IOP (P<0.001), longer axial length (P<0.001),
      and thinner central cornea (P = 0.006) were associated with POAG. CONCLUSIONS:
      High prevalence rates of POAG (4.0%) and POAG with normal IOP levels (3.3%),
      which were comparable with those on the Japanese mainland, were found in a
      southwestern rural island of Japan, where the prevalence of primary angle-closure
      glaucoma (previously reported as 2.2%) was considerably higher than on the
      Japanese mainland (0.6% in the Tajimi Study) or other countries. The risk factors
      for POAG included male gender, older age, higher IOP, myopia, and a thinner
      cornea.

PMID- 24746387
TI  - Investigating inherent functional differences between human cardiac fibroblasts
      cultured from nondiabetic and Type 2 diabetic donors.
AB  - INTRODUCTION: Type 2 diabetes mellitus (T2DM) promotes adverse myocardial
      remodeling and increased risk of heart failure; effects that can occur
      independently of hypertension or coronary artery disease. As cardiac fibroblasts
      (CFs) are key effectors of myocardial remodeling, we investigated whether
      inherent phenotypic differences exist in CF derived from T2DM donors compared
      with cells from nondiabetic (ND) donors. METHODS: Cell morphology (cell area),
      proliferation (cell counting over 7-day period), insulin signaling [phospho-Akt
      and phospho-extracellular signal-regulated kinase (ERK) Western blotting], and
      mRNA expression of key remodeling genes [real-time reverse transcription
      polymerase chain reaction (RT-PCR)] were compared in CF cultured from atrial
      tissue from 14 ND and 12 T2DM donors undergoing elective coronary artery bypass
      surgery. RESULTS: The major finding was that Type I collagen (COL1A1) mRNA levels
      were significantly elevated by twofold in cells derived from T2DM donors compared
      with those from ND donors; changes reflected at the protein level. T2DM cells had
      similar proliferation rates but a greater variation in cell size and a trend
      towards increased cell area compared with ND cells. Insulin-induced Akt and ERK
      phosphorylation were similar in the two cohorts of cells. CONCLUSION: CF from
      T2DM individuals possess an inherent profibrotic phenotype that may help to
      explain the augmented cardiac fibrosis observed in diabetic patients. MINI
      SUMMARY: We investigated whether inherent phenotypic differences exist between CF
      cultured from donors with or without Type 2 diabetes. Cell morphology,
      proliferation, insulin signaling, and gene expression were compared between
      multiple cell populations. The major finding was that Type I collagen levels were
      elevated in fibroblasts from diabetic donors, which may help explain the
      augmented cardiac fibrosis observed with diabetes.

PMID- 24746388
TI  - Virtual planning in orthognathic surgery.
AB  - Numerous publications regarding virtual surgical planning protocols have been
      published, most reporting only one or two case reports to emphasize the hands-on
      planning. None have systematically reviewed the data published from clinical
      trials. This systematic review analyzes the precision and accuracy of three
      dimensional (3D) virtual surgical planning of orthognathic procedures compared
      with the actual surgical outcome following orthognathic surgery reported in
      clinical trials. A systematic search of the current literature was conducted to
      identify clinical trials with a sample size of more than five patients, comparing
      the virtual surgical plan with the actual surgical outcome. Search terms revealed
      a total of 428 titles, out of which only seven articles were included, with a
      combined sample size of 149 patients. Data were presented in three different
      ways: intra-class correlation coefficient, 3D surface area with a difference
      <2mm, and linear and angular differences in three dimensions. Success criteria
      were set at 2mm mean difference in six articles; 125 of the 133 patients included
      in these articles were regarded as having had a successful outcome. Due to
      differences in the presentation of data, meta-analysis was not possible. Virtual
      planning appears to be an accurate and reproducible method for orthognathic
      treatment planning. A more uniform presentation of the data is necessary to allow
      the performance of a meta-analysis. Currently, the software system most often
      used for 3D virtual planning in clinical trials is SimPlant (Materialise). More
      independent clinical trials are needed to further validate the precision of
      virtual planning. 

PMID- 24746389
TI  - Report on the World Diabetes Congress 2013, Melbourne.

PMID- 24746390
TI  - Dimensional assessment of posttraumatic stress disorder in DSM-5.
AB  - The present paper describes the development of the National Stressful Events
      Survey for PTSD-Short Scale (NSESSS-PTSD), a new self-report scale for PTSD that
      is brief (9 items), free of copyright restrictions, and consistent with DSM-5
      diagnostic criteria. Study 1 describes the development of the NSESSS-PTSD scale
      items, which were reduced from a larger pool of items that were administered to a
      subsample of individuals with probable DSM-5 PTSD diagnoses from a large national
      sample. The resultant scale included items from each criterion and demonstrated
      high internal consistency. Study 2 evaluates the psychometric properties of the
      NSESSS-PTSD in a trauma-exposed non-clinical sample. Strong psychometric
      properties were observed in the sample, including convergent validity (through
      comparison to the DSM-IV Posttraumatic Stress Disorder Checklist), internal
      consistency, and the presence of a single dominant factor. Limitations of the
      present studies are discussed and specific recommendations for the next steps in
      the validation process are provided. 

PMID- 24746391
TI  - The Hamilton Depression Scale (HAM-D) and the Montgomery-Asberg Depression Scale
      (MADRS). A psychometric re-analysis of the European genome-based therapeutic
      drugs for depression study using Rasch analysis.
AB  - The objective of this re-analysis of the European Genome-Based Therapeutic Drugs
      for Depression Study (GENDEP) was to psychometrically test the unidimensionality
      of the full Montgomery Asberg Depression Rating Scale (MADRS10) and the Hamilton
      Depression Scale (HAM-D17) versus their respective subscales (MADRS5 and HAM-D6)
      containing the core symptoms of depression severity. Rasch analysis was applied
      using RUMM 2030 software to assess the overall fit for unidimensionality. Neither
      the MADRS10 nor the HAM-D17 was found to fit the Rasch model for
      unidimensionality. The HAM-D6 (containing the items of depressed mood, guilt,
      work and interests, psychomotor retardation, psychic anxiety, and somatic
      general) as well as the analogue MADRS5 were tested for unidimensionality by use
      of the RUMM 2030 programme, and only the HAM-D6 was accepted. When testing for
      invariance across rating weeks or centres, the RUMM 2030 had to be supplemented
      with the Friedman two-way analysis of variance by ranks. The HAM-D6 but not the
      MADRS5 was accepted. It was therefore concluded that the HAM-D6 is a
      psychometrically valid outcome scale to measure change in clinical trials of
      antidepressants. 

PMID- 24746392
TI  - Chasing losses in online poker and casino games: characteristics and game play of
      Internet gamblers at risk of disordered gambling.
AB  - Disordered Internet gambling is a psychological disorder that represents an
      important public health issue due to the increase in highly available and
      conveniently accessible Internet gambling sites. Chasing losses is one of the few
      observable markers of at-risk and problem gambling that may be used to detect
      early signs of disordered Internet gambling. This study examined loss chasing
      behaviour in a sample of Internet casino and poker players and the socio
      demographic variables, irrational beliefs, and gambling behaviours associated
      with chasing losses. An online survey was completed by 10,838 Internet gamblers
      (58% male) from 96 countries. The results showed that Internet casino players had
      a greater tendency to report chasing losses than poker players and gamblers who
      reported chasing losses were more likely to hold irrational beliefs about
      gambling and spend more time and money gambling than those who reported that they
      were unaffected by previous losses. Gamblers who played for excitement and to win
      money were more likely to report chasing losses. This study is one of the largest
      ever studies of Internet gamblers and the results are highly significant as they
      provide insight into the characteristics and behaviours of gamblers using this
      mode of access. 

PMID- 24746393
TI  - Personality organization in borderline patients with a history of suicide
      attempts.
AB  - Suicide attempts (SA) are common in patients with Borderline Personality Disorder
      (BPD). Recent studies focus on aspects of personality associated with risk for SA
      such as deficits in affect regulation including impulse control and aggression.
      The current study examines associations of dysfunctional personality
      organization, psychiatric comorbidities as well as non-suicidal self-injury
      (NSSI) with SA in a sample of 68 BPD outpatients. Patients with a history of SA
      yielded higher scores in personality domains of aggression, especially self
      directed aggression. Further, a history of SA was associated with a worse general
      level of personality organization and a higher prevalence rate of NSSI and
      substance abuse disorder. The results demonstrate that SA in BPD patients might
      be regarded as a manifestation of impaired personality functioning rather than
      mere state variables and symptoms. Moreover, these findings might have
      implications for indication, treatment, and prognosis of Borderline Personality
      Disorder. 

PMID- 24746394
TI  - [Cerebrotendinous xanthomatosis: a multicentric retrospective study of 15 adults,
      clinical and paraclinical typical and atypical aspects].
AB  - INTRODUCTION: Cerebrotendinous xanthomatosis, a metabolic leukodystrophy with an
      autosomal recessive inheritance, is secondary to deficiency of sterol 27
      hydroxylase, an enzyme involved in cholesterol catabolism. Classical symptoms
      include clinical or infraclinical xanthomas affecting the skin and tendons, early
      cataracts, neurological signs and diarrhea. Brain imaging reveals involvement of
      the dentate nuclei and periventricular white matter hyperintensities. The
      diagnosis is based on an increased cholestanol level in serum, confirmed by the
      presence of a mutation in the CYP27A1 gene. Treatment is based on
      chenodeoxycholic acid. METHOD: We report a retrospective multicentric study of 15
      cases of cerebrotendinous xanthomatosis diagnosed in French adults. Clinical,
      molecular and MRI findings were recorded in all patients. RESULTS: The average
      age at diagnosis was 39years (range 27-65). Disease onset occurred in childhood
      in 73% of patients and in adulthood in 27%. All patients with a pediatric onset
      were diagnosed during adulthood (age range 28-65years). Clinical symptoms
      variably associated cerebellar syndrome, pyramidal syndrome, cognitive decline,
      epilepsy, neuropathy (sought in 10 of our patients, present in forms in 8),
      psychiatric disorders, cataract and xanthomas. One patient had an atypical
      presentation: monoparesis associated with xanthomas. Brain MRI was abnormal in
      all: findings consisted in T2-weighted hyperintensity of the dentate nuclei
      (47%), periventricular leuoencephalopathy (73%) which preferentially involved the
      posterior cerebral part (60%), leucoencephalopathy with a vascular pattern (7%),
      hyperintensity of the cortico-spinal tracts (53%), globi pallidi, corpus callosum
      and cerebral atrophy (33%). Serum cholestanol was elevated in 93% of patients.
      The most frequent mutation was 1183C>T (n=5/15). Under treatment with
      chenodeoxycholic acid, eight patients improved initially, followed by
      stabilization in five of them, and worsening in the others. Four patients died.
      CONCLUSION: Patients with the xanthoma-neurological disorder association should
      be tested for cerebrotendinous xanthomatosis. The disease often begins in
      childhood with a diagnostic delay but also in adulthood. Involvement of the
      dentate nuclei is specific but not sensitive and the supratentorial
      leucoencephalopathy is not specific but with an antero-posterior gradient. A
      vascular distribution and involvement of the corpus callosum are possible. Serum
      cholestanol assay is very reliable: an elevated level provides the diagnosis,
      which must nevertheless be confirmed by molecular biology.

PMID- 24746396
TI  - Transmucosal core needle biopsy: a novel diagnostic approach to oral and
      oropharyngeal lesions.
AB  - PURPOSE: Oral and oropharyngeal tumors have often been characterized by a deep
      submucosal growth pattern under an intact mucous membrane. This will be
      particularly true for lesions of the tongue and could be associated with relevant
      difficulties regarding diagnosis and treatment planning. We hypothesized that the
      transoral transmucosal application of a core needle biopsy (CNB) for lesions of
      the tongue, the base of the tongue, and the floor of the mouth could be of
      considerable clinical usefulness for many patients. It has only previously been
      described in single cases and has not yet been separately discussed. MATERIAL AND
      METHODS: We report on the novel transoral use of CNB during rigid endoscopy with
      the patient under general anesthesia, with an emphasis on lesions of the tongue.
      A series of cases and illustrative patients are presented. RESULTS: Transmucosal
      CNB was accurate and of considerable clinical usefulness in all cases. The
      relevant advantages of this technique compared with conventional biopsy using
      biopsy forceps and transmucosal fine needle aspiration are presented.
      CONCLUSIONS: The transoral transmucosal approach to the submucosal space of the
      oral cavity and the oropharynx has further extended the field of application of
      CNB. In selected patients, this CNB approach offers essential diagnostic
      benefits, in particular, for tumors of the tongue.

PMID- 24746395
TI  - Solitary tuberculous brain lesions: 24 new cases and a review of the literature.
AB  - A solitary tuberculous brain lesion (STBL) can be difficult to distinguish from a
      glioma, metastasis or other infectious disease, especially from a pyogenic brain
      abscess. We analyzed the clinical characteristics, diagnostic procedures and
      outcomes of 24 patients with STBL diagnosed in three centers from France, India
      and Mexico. We also reviewed 92 STBL cases previously reported in the literature.
      General symptoms were found in 54% of our patients, including enlarged lymph
      nodes in 20%. Cerebrospinal fluid was typically abnormal, with lymphocytic
      pleocytosis and a high protein level. The lung CT scan was abnormal in 56% of
      patients, showing lymphadenopathy or pachipleuritis. Brain MRI or CT was always
      abnormal, showing contrast-enhanced lesions. Typically, MRI abnormalities were
      hypointense on T1-weighted sequences, while T2-weighted sequences showed both a
      peripheral hypersignal and a central hyposignal. The diagnosis was documented
      microbiologically or supported histologically in 71% of cases. Clinical outcome
      was good in 83% of cases. 

PMID- 24746397
TI  - Influence of the changes in arch width on postsurgical relapse after mandibular
      setback surgery with minimal orthodontics.
AB  - PURPOSE: Most reports on the surgery-first approach in patients with skeletal
      Class III malocclusion have focused on skeletal changes and treatment efficacy.
      This study sought to evaluate the association between the transverse changes of
      arch dimension and postsurgical relapse of the mandible after mandibular setback
      surgery (MS) with minimal orthodontic preparation (MO) without extractions (N).
      MATERIALS AND METHODS: This was a retrospective cohort study. The sample
      consisted of patients with skeletal Class III malocclusion who underwent MS-MO/N.
      Primary outcome variables were horizontal, vertical, and angular changes of the
      mandibular position (mandibular relapse). Predictor variables included changes in
      the transverse width of the upper and lower arches. Lateral cephalograms and
      study models were obtained and measured before (T0) and 1 month (T1), 3 months
      (T2), and 6 months (T3) after surgery. Descriptive, paired t test, repeated
      measures analysis of variance, and a generalized estimating equation with
      Bonferroni correction were computed. RESULTS: The sample consisted of 12 patients
      (7 female and 5 male; mean age, 19.83 +/- 2.37 yr). Significant anterior and
      superior movements and counterclockwise rotation of the mandible were noted from
      T1 to T3. Despite dental decompensation from T1 to T3, there were no significant
      postsurgical changes in arch width. In addition, there was no correlation between
      the forward and upward movements of the mandible and changes of arch width.
      However, the counterclockwise rotation of the mandible was correlated with the
      changes in the upper inter-first premolar width (UIP1W) and lower inter-first
      molar width (LIM1W) over time. CONCLUSION: The changes in arch width had no
      association with horizontal and vertical relapses of the mandible. Only changes
      in UIP1W and LIM1W showed an association with angular relapse of the mandible.

PMID- 24746398
TI  - Schneiderian membrane detachment using transcrestal hydrodynamic ultrasonic
      cavitational sinus lift: a human cadaver head study and histologic analysis.
AB  - PURPOSE: Recent studies have suggested the osteogenic layer of the periosteum at
      the base of the sinus membrane to play a key role in bone regeneration after
      sinus lift procedures. Thus, atraumatic detachment of the sinus membrane with an
      intact periosteum seems mandatory. The present histologic study of fresh human
      cadaver heads investigated the detachment behavior and histologic integrity of
      the detached periosteum after application of the transcrestal hydrodynamic
      ultrasonic cavitational sinus lift (tHUCSL-INTRALIFT). MATERIALS AND METHODS: A
      total of 15 sinuses in 8 fresh human cadaver heads were treated using tHUCSL
      INTRALIFT. After surgery, they were checked macroscopically for damage to the
      sinus membrane and then processed for histologic inspection under light
      microscopy. A total of 150 histologic specimens, randomly selected from the core
      surgical sites, were investigated using hematoxylin-eosin (HE), Azan, and
      trichrome staining. RESULTS: None of the 150 inspected specimens showed any
      perforation or dissection of the periosteum from the subepithelial connective
      tissue and respiratory epithelium and were fully detached from the bony antrum
      floor. The connecting Sharpey fibers revealed to be cleanly separated from the
      sinus floor in all specimens. CONCLUSIONS: The results of the present study
      suggest tHUCSL-INTRALIFT should be used to perform predictable and safe
      detachment of the periosteum from the bony sinus floor as a prerequisite for
      undisturbed and successful physiologic subantral bone regeneration.

PMID- 24746399
TI  - Facial trauma evaluation leading to a diagnosis of delayed splenic rupture.
AB  - A patient presented 48 hours after falling and sustaining facial fractures and
      was evaluated in an outpatient setting. The patient had been seen at 2 other
      hospitals, including a level I trauma center, and discharged home. While
      undergoing evaluation for his facial trauma, the patient became severely
      hypotensive. The patient was diagnosed with a delayed splenic rupture and
      underwent splenectomy. 

PMID- 24746400
TI  - Boosting the sterile insect technique to control mosquitoes.
AB  - Mosquitoes are vectors of major diseases. Auto-dissemination recently proved very
      efficient to control Aedes species, using adult females contaminated with
      dissemination stations of juvenile hormone to treat breeding habitats, but cannot
      be used at large scales. Here we propose to combine it to the Sterile Insect
      Technique (SIT) to create a new control concept, named 'boosted SIT' that might
      enable the area-wide eradication of mosquitoes and many other vectors and insect
      pests. 

PMID- 24746401
TI  - [Suggestions on post mortem molecular microbiology analysis].

PMID- 24746402
TI  - Presence of quinolone resistance to qnrB1 genes and blaOXA-48 carbapenemase in
      clinical isolates of Klebsiella pneumoniae in Spain.
AB  - A study is presented on the presence of quinolone resistance qnrB1 genes in
      clinical isolates belonging to the largest series of infections caused by OXA-48
      producing Klebsiella pneumoniae in a single-centre outbreak in Spain. Evidence is
      also provided, according to in vitro results, that there is a possibility of co
      transfer of plasmid harbouring blaOXA-48 with an other plasmid harbouring qnrB1
      in presence of low antibiotic concentrations of fluoroquinolones, showing the
      risk of multi-resistance screening. 

PMID- 24746403
TI  - Long-term management of patients with disorders of sex development (DSD).
AB  - Differences or disorders of sex development (DSD) describe a biological
      discrepancy between chromosomal, gonadal, and phenotypical sex, often affecting
      the morphology of the genito-reproductive organs. DSD is most often due to
      genetic abnormalities affecting chromosomal composition or single genes. Most
      children with 46,XX karyotype and DSD have congenital adrenal hyperplasia due to
      21-hydroxylase deficiency and should be regarded as unchallenged females. For
      children with 46,XY DSD, the situation is even much more complicated since indeed
      an exact genetic diagnosis is still missing. Depending on the phenotype, this may
      be true for more than 80% of children with severe hypospadias, in contrast in
      post-pubertal patients with clinical evidence of complete androgen insensitivity,
      whom 95% show an underlying mutation within the androgen receptor gene. DSD and
      numerical aberrations of sex chromosomes, especially 45,X/46,XY mosaicism depends
      essentially on the assessment of the exact clinical morphology with a focus of
      the external and internal genital structures and of the endocrine and
      reproductive function of the gonads with the aim for a best prognosis of the
      child. This assessment should be done in a center of expertise. 

PMID- 24746404
TI  - Results from the Swedish national anterior cruciate ligament register.
AB  - PURPOSE: The purpose of the study was to analyze the baseline variables and
      clinical outcomes for almost 24,000 patients entered into the Swedish National
      ACL Register between January 2005 and December 2012. METHODS: The register
      consists of 2 parts: 1 section in which surgeons report baseline and surgical
      data and 1 section in which patients report the Knee Injury and Osteoarthritis
      Outcome Score (KOOS) and the EQ-5D score before and 1, 2, and 5 years after
      surgery. RESULTS: By December 2012, 23,744 patients had been entered into the
      surgeons' part of the register. The female-male ratio in the register is 42:58.
      The mean age at primary anterior cruciate ligament (ACL) reconstruction was 26
      years (SD, 11 years) and 28 years (SD, 9 years) for the female and male patients,
      respectively. The ACL injury occurred during soccer in 36% of the female patients
      and 49% of the male patients. In 2012, 95% of the primary ACL reconstructions
      were performed using hamstring tendon autografts. For patients who had a minimum
      of 5 years' follow-up, the revision rate was 3.3% and the contralateral
      reconstruction rate was 3.8%. On all follow-up occasions up to 5 years, patients
      who had undergone revision had a significantly (P < .001) poorer outcome than
      those who had undergone primary unilateral ACL reconstructions in all KOOS and EQ
      5D dimensions. On all follow-up occasions, smokers obtained significantly poorer
      scores than nonsmokers in terms of both the KOOS (P < .008) and the EQ-5D (P <
      .024). CONCLUSIONS: Soccer is the most common cause of injury in both female and
      male patients, and patients undergoing revisions fare less well than those
      undergoing primary unilateral ACL reconstructions, as well as bilateral
      reconstructions. Furthermore, smokers fare less well than nonsmokers. The
      cumulative risk of an ACL revision or contralateral ACL reconstruction during a 5
      year period is approximately 7%. For patients aged younger than 19 years, the
      cumulative risk is significantly higher. LEVEL OF EVIDENCE: Level II,
      retrospective prognostic study.

PMID- 24746405
TI  - The hip-spine syndrome: how does back pain impact the indications and outcomes of
      hip arthroscopy?
AB  - PURPOSE: Many patients presenting with hip disease also have coexisting lumbar
      spine disease (LSD). At present there is a paucity of literature examining the
      effect of arthroscopic hip surgery in patients with coexisting LSD. The purpose
      of this systematic review was to examine the relationship between the hip and
      lumbar spine to determine whether low back pain impacts the indications and
      outcomes for surgical intervention of the hip. METHODS: A systematic review of
      the literature was performed by a search of PubMed using the following search
      terms: (1) hip, back, and motion; (2) hip, back, and pain; and (3) hip, lumbar
      spine, and pain. Two reviewers searched for relevant articles that met
      established inclusion criteria. We excluded review articles, technique articles,
      articles reporting on the same patient population, and articles without reported
      patient data. Kinematic data pertaining to the hip for patients with low back
      pain was collected. Preoperative and postoperative data were collected for
      patients treated for hip disease in the setting of LSD. RESULTS: After examining
      2,020 references and abstracts, 15 articles were selected for this review.
      Patients with low back pain consistently demonstrated decreased hip range of
      motion compared with controls. Patients undergoing hip surgery with coexisting
      LSD showed improvement in the modified Harris Hip Score (mHHS), Harris Hip Score
      (HHS), Visual Analog Scale (VAS), SF-36 scores, and the Owestry Disability Index.
      CONCLUSIONS: Patients with low back pain frequently have limited or altered hip
      range of motion, and these patients routinely improve after surgical intervention
      for hip disease. Surgical intervention for hip disease should be considered in
      the context of low back pain and LSD. LEVEL OF EVIDENCE: Level IV, systematic
      review of Level III and IV studies.

PMID- 24746406
TI  - Follow-up of a new arthroscopic technique for implantation of matrix-encapsulated
      autologous chondrocytes in the knee.
AB  - PURPOSE: The purpose of this study was to evaluate the clinical and sequential
      imaging follow-up results at a mean of 36 months after an arthroscopic technique
      for implantation of matrix-encapsulated autologous chondrocytes for the treatment
      of articular cartilage lesions on the femoral condyles. METHODS: Ten patients
      underwent arthroscopic implantation of autologous chondrocytes seeded onto a
      bioabsorbable scaffold. The patients were evaluated clinically using a visual
      analog scale (VAS) for pain and International Knee Documentation Committee
      (IKDC), Lysholm, and Tegner scores. Magnetic resonance imaging (MRI) T2-mapping
      and magnetic resonance observation of cartilage repair tissue (MOCART)
      evaluations were also performed. Second-look arthroscopic evaluation using the
      International Cartilage Repair Society (ICRS) grading classification was
      performed at 12 months. RESULTS: Compared with their preoperative values, at 36
      months mean values +/- standard deviation for the VAS scale for pain were 6.0 +/-
      1.5 to 0.3 +/- 0.4. Improvement in clinical scores between preoperative values
      and 36-month follow-up values in subjective IKDC scores was 46.9 +/- 18.5 to 77.2
      +/- 12.8; in Lysholm scores, it was 51.8 +/- 25.1 to 87.9 +/- 6.5, and in the
      Tegner activity scale it was 2.9 +/- 1.7 to 5.9 +/- 1.9. Mean T2 mapping and
      MOCART scores improved over time to 38.1 +/- 4.4 ms and 72.5 +/- 10,
      respectively. Mean ICRS score by second-look arthroscopy at 1 year was 10.4 +/-
      0.1. CONCLUSIONS: All clinical scores improved over time compared with the
      preoperative values. Clinical results are comparable with MRI T2 mapping and ICRS
      evaluations, suggesting that this arthroscopic technique for cell-based cartilage
      repair is efficacious and reproducible at a mean of 36 months of follow-up. LEVEL
      OF EVIDENCE: Level IV, therapeutic case series.

PMID- 24746407
TI  - Test re-test reliability of centre of pressure measures during standing balance
      in individuals with knee osteoarthritis.
AB  - Assessment of changes in standing balance following an intervention requires
      accurate measurement of balance parameters. The reliability of centre of pressure
      measures of balance during single-leg standing has not been reported in
      individuals with knee osteoarthritis. The purpose of this study was to assess the
      test re-test reliability of force platform centre of pressure measures during
      single-leg standing in older adults with knee osteoarthritis. Twenty-five adults
      with radiographic evidence of knee osteoarthritis performed single-leg standing
      balance trials on a laboratory-grade force platform on two occasions, no more
      than 14 days apart. Participants were asked to stand on their more symptomatic
      limb for three, ten second trials. Centre of pressure measures collected
      included: standard deviation in the mediolateral and anteroposterior directions,
      mean path length, velocity, and area. The mean of the three trials was
      calculated. Intraclass correlation coefficients, standard error of measurement,
      Bland and Altman plots and the minimum detectable change were calculated.
      Intraclass correlation coefficients ranged from 0.54 to 0.87, suggesting mixed
      reliability of measures. Reliability was lowest for the centre of pressure area
      (intraclass correlation coefficient=0.54), and highest for centre of pressure
      velocity and path length (intraclass correlation coefficient=0.87 for both).
      Standard error of measurement values were low for standard deviation in the
      mediolateral direction and high for centre of pressure area. These results
      suggest that centre of pressure values, in particular path length and velocity,
      are appropriate for assessment of standing balance in people with medial knee
      osteoarthritis. 

PMID- 24746408
TI  - Pharyngeal entomophthoromycosis.
AB  - We describe a rare case of entomophthoromycosis of the pharynx in a previously
      healthy patient, unlike other fungal infections which are seen as opportunistic
      infections in immunocompromised hosts. This infection is commonly seen in
      subtropical and tropical areas of Africa, America, and Asia. Painless,
      erythematous, indurated plaques of subcutaneous tissue are characteristic of this
      infection. There are currently no standard antifungal regimens for this
      infection, making treatment difficult. An endoscopic surgical wide resection of
      the lesion was performed, itraconazole was administered, and the patient improved
      clinically. 

PMID- 24746409
TI  - The effect of polymer properties on direct compression and drug release from
      water-insoluble controlled release matrix tablets.
AB  - The objective of this study was to identify and evaluate key polymer properties
      affecting direct compression and drug release from water-insoluble matrices.
      Commonly used polymers, such as Kollidon((r)) SR, Eudragit((r)) RS and ethyl
      cellulose, were characterized, formulated into tablets and compared with regard
      to their properties in dry and wet state. A similar site percolation threshold of
      65% v/v was found for all polymers in dry state. Key parameters influencing
      polymer compactibility were the surface properties and the glass transition
      temperature (T(g)), affecting polymer elasticity and particle size-dependent
      binding. The important properties observed in dry state also governed matrix
      characteristics and therefore drug release in wet state. A low T(g)
      (Kollidon((r)) SR<Eudragit((r)) RS) decreased the percolation threshold, particle
      size effect and tortuosity, but increased permeability and sensitivity to
      heat/humidity treatment. Hence, lower permeability and higher stability are
      benefits of a high-T(g) polymer (ethyl cellulose). However, release retardation
      was observed in the same order as matrix integrity (Eudragit((r)) RS<ethyl
      cellulose<Kollidon((r)) SR), as the high permeability was counteracted by PVP in
      case of Kollidon((r)) SR. Therefore, the Tg and composition of a polymer need to
      be considered in polymer design and formulation of controlled-release matrix
      systems.

PMID- 24746410
TI  - Dextran-protamine coated nanostructured lipid carriers as mucus-penetrating
      nanoparticles for lipophilic drugs.
AB  - The main objectives of the present study were (i) to evaluate the effect of the
      mucus layer on saquinavir-loaded nanostructured lipid carriers (SQV-NLCs) uptake
      and (ii) to evaluate the mucopenetrating properties of dextran-protamine (Dex
      Prot) coating on NLCs as per SQV permeability enhancement. Three different NLC
      formulations differing on particle size and surfactant content were obtained and
      coated with Dex-Prot complexes. SQV permeability was then evaluated across Caco-2
      cell monolayers (enterocyte-like model) and Caco-2/HT29-MTX cell monolayers
      (mucus model). In the Caco-2 monolayers, Dex-Prot-NLCs increased up to 9-fold SQV
      permeability in comparison to uncoated nanoparticles. In the Caco-2/HT29-MTX
      monolayers, Dex-Prot-NLCs presenting a surface charge close to neutrality
      significantly increased SQV permeability. Hence, Dex-Prot complex coating is a
      promising strategy to ensure successful nanoparticle mucus-penetration, and thus,
      an efficient nanoparticle oral delivery. To our knowledge, this is the first time
      that Dex-Prot coating has been described as a nanoparticle muco-penetration
      enhancer across the intestinal mucus barrier.

PMID- 24746411
TI  - Taste acceptability of pulverized brand-name and generic drugs containing
      amlodipine or candesartan.
AB  - Trials with pulverized brand-name antihypertensive drugs suggest that, from the
      perspective of taste acceptability, crushed candesartan, chlortalidon,
      hydrochlorothiazide, lercanidipine and lisinopril should be preferred to
      pulverized amlodipine, atenolol, bisoprolol, enalapril, irbesartan, losartan,
      ramipril, telmisartan and valsartan. Brand-name antihypertensive drugs and the
      corresponding generic medicines have never been compared with respect to their
      taste acceptability. We therefore investigated among healthy health care workers
      the taste acceptability of a pulverized 1 mg-test dose of the brand-name and two
      generics containing either the dihydropyridine calcium-channel blocker amlodipine
      (Norvasc((r)), Amlodipin-Mepha((r)) and Amlodipin Pfizer((r))) or the angiotensin
      receptor antagonist candesartan (Atacand((r)), Cansartan-Mepha((r)) and
      Pemzek((r))). For this purpose, a smiley-face scale depicting four degrees of
      pleasure was used. Between November and December 2013, the taste test was
      performed among 19 nurses (15 female and 4 male subjects) and 12 physicians (5
      female and 7 male subjects) aged between 25 and 49 years. Pulverized brand-names
      and generics containing either amlodipine or candesartan did not differ with
      respect to their taste acceptability.

PMID- 24746412
TI  - Encapsulation of poorly water-soluble drugs into organic nanotubes for improving
      drug dissolution.
AB  - Hydrocortisone (HC), a poorly water-soluble drug, was encapsulated within organic
      nanotubes (ONTs), which were formed via the self-assembly of N-{12-[(2-alpha,beta
      d-glucopyranosyl) carbamoyl]dodecanyl}-glycylglycylglycine acid. The stability of
      the ONTs was evaluated in ten organic solvents, of differing polarities, by field
      emission transmission electron microscopy. The ONTs maintained their stable
      tubular structure in the highly polar solvents, such as ethanol and acetone.
      Furthermore, solution-state (1)H-NMR spectroscopy confirmed that they were
      practically insoluble in acetone at 25 degrees C (0.015 mg/mL). HC-loaded ONTs
      were prepared by solvent evaporation using acetone. A sample with a 3/7 weight
      ratio of HC/ONT was analyzed by powder X-ray diffraction, which confirmed the
      presence of a halo pattern and the absence of any crystalline HC peak. HC peak
      broadening, observed by solid-state (13)C-NMR measurements of the evaporated
      sample, indicated the absence of HC crystals. These results indicated that HC was
      successfully encapsulated in ONT as an amorphous state. Improvements of the HC
      dissolution rate were clearly observed in aqueous media at both pH 1.2 and 6.8,
      probably due to HC amorphization in the ONTs. Phenytoin, another poorly water
      soluble drug, also showed significant dissolution improvement upon ONT
      encapsulation. Therefore, ONTs can serve as an alternative pharmaceutical
      excipient to enhance the bioavailability of poorly water-soluble drugs.

PMID- 24746413
TI  - Novel organic salts based on fluoroquinolone drugs: synthesis, bioavailability
      and toxicological profiles.
AB  - In order to overcome the problems associated with low water solubility, and
      consequently low bioavailability of active pharmaceutical ingredients (APIs),
      novel organic salts containing fluoroquinolones (e.g. ciprofloxacin and
      norfloxacin) were prepared, using an optimized synthetic procedure based on
      direct protonation, with different biocompatible counter ions such as mesylate,
      gluconate and glycolate. All the prepared organic salts were characterized by
      spectroscopic techniques, mass spectrometry and thermal analysis. Solubility
      studies in water and simulated biological fluids at 25 degrees C and 37 degrees C
      were also performed. Additionally, octanol-water and phospholipid-water partition
      coefficients were measured at 25 degrees C. The cytotoxicity and anti
      inflammatory efficacy using an human cell model of intestinal epithelia (Caco-2
      cells) were also evaluated and compared to those of the parent APIs. The adequate
      selection of the biocompatible anions allows the tuning of important physical,
      thermal and toxicological properties.

PMID- 24746414
TI  - Instantaneous enteric nano-encapsulation of omeprazole: pharmaceutical and
      pharmacological evaluation.
AB  - Recently, great attention has been paid to nanocapsules. The interest of these
      structures is due to their promising applications as drug delivery systems. The
      objective of this study was to develop novel enteric coating technique based on
      instantaneous encapsulation of the acid-labile drug, omeprazole in innovative
      enteric nanocapsules. Omeprazole enteric nanocapsules were formulated by varying
      the type and amount of the enteric polymer. The particle size (PS),
      polydispersity index (PDI), zeta potential (ZP) and encapsulation efficiency (EE)
      values of the prepared enteric nanocapsules were determined. A full 2(1)*3(1)
      factorial design was used for planning and analysis of the experimental trials to
      select the optimized formulation. The highest desirability value was 0.7463 for
      formula E3 (containing 200mg hydroxypropyl methylcellulose phthalate (HPMCP)).
      The stability of omeprazole was reflected by the absence of the exothermal peak
      when the drug was encapsulated as detected by differential scanning calorimetry
      (DSC) thermograms. In vitro drug release study confirmed the USP specifications
      required to meet the key formulation characteristics of gastro-resistance. In
      vivo pharmacological assessment showed that the optimized nanocapsules were able
      to protect rat stomach against ulcer formation compared to the aqueous suspension
      of the drug which showed less significant protection. 

PMID- 24746415
TI  - beta-Cyclodextrin-dextran polymers for the solubilization of poorly soluble
      drugs.
AB  - The aim of this study was to assess the potential of novel beta-cyclodextrin
      (betaCD)-dextran polymers for drug delivery. The size distribution of betaCD
      dextrans (for eventual parenteral administration), the influence of the dextran
      backbones on the stability of the betaCD/drug complex, the solubilization
      efficiency of poorly soluble drugs and drug release properties were investigated.
      Size analysis of different betaCD-dextrans was measured by size exclusion
      chromatography (SEC) and asymmetrical flow field-flow fractionation (AF4).
      Stability of drug/betaCD-dextrans was assessed by isothermal titration
      calorimetry (ITC) and molar enthalpies of complexation and equilibrium constants
      compared to some commercially available betaCD derivatives. For evaluation of the
      solubilization efficiency, phase-solubility diagrams were made employing
      hydrocortisone (HC) as a model of poorly soluble drugs, whereas reverse dialysis
      was used to detect potential drug supersaturation (increased molecularly
      dissolved drug concentration) as well as controlled release effects. Results
      indicate that all investigated betaCD-polymers are of appropriate sizes for
      parenteral administration. Thermodynamic results demonstrate that the presence of
      the dextran backbone structure does not affect the stability of the betaCD/drug
      complex, compared to native betaCD and commercially available derivatives.
      Solubility studies evidence higher solubilizing abilities of these new polymers
      in comparison to commercially available betaCDs, but no supersaturation states
      were induced. Moreover, drug release studies evidenced that diffusion of HC was
      influenced by the solubilization induced by the betaCD-derivatives. 

PMID- 24746416
TI  - The effect of shear and extensional viscosity on atomization in medical inhaler.
AB  - The paper contains the results of experimental studies of water, aqueous
      solutions of glycerol and aqueous solutions of glycerol-polyethylene oxide (PEO)
      atomization process in a medical inhaler obtained by the use of the digital
      microphotography method. The effect of the shear and extensional viscosity on the
      drop size, drop size histogram and mean drop diameter has been analyzed. The
      obtained results have shown that the drop size increases with the increase in
      shear and extensional viscosity of liquid atomized. Extensional viscosity has a
      greater impact on the spraying process. It has been shown that the change in
      liquid viscosity leads to significant changes in drop size distribution. The
      correlation for Sauter mean diameter as function of the shear and extensional
      viscosity was proposed. 

PMID- 24746417
TI  - Diabetes outcomes within integrated healthcare management programs.
AB  - AIM: The aim of this observational study was to assess mortality of patients with
      type 2 diabetes by type of healthcare delivery system, i.e. through specialist
      centers or generalist doctors, or integrated care. METHODS: The study was
      conducted at the "Vicentino Ovest" Local Health District in the Veneto Region
      (north-eastern Italy) from January 1, 2008 to December 31, 2010. Patients with
      diabetes (>= 20 years old) were identified using different public health
      databases. They were grouped as: patients followed up by specialists at diabetes
      clinics (DS); patients seen only by their own general practitioner (GP); and
      patients receiving integrated care (DS-GP). Cox's regression analysis was used to
      estimate adjusted hazard ratios for available potential predictors of death by
      level of care. RESULTS: The crude mortality rate was highest in the GP group
      (26.1 per 1000 person-years), the difference being minimal when compared with the
      DS group (21.7 per 1000 person-years) and more marked when compared with the DS
      GP group (8.8 per 1000 person-years). Patients followed up by their GPs had a 2.7
      adjusted RR for mortality by comparison with the DS-GP group. CONCLUSIONS: The
      findings of the present study could demonstrate that it is safe and cost
      effective, after a first specialist assessment at a diabetes service, for low
      risk diabetic patients to be managed by family physicians as part of a
      coordinated care approach, based on the specialist's clinical recommendations;
      GPs can subsequently refer patients to a specialist whenever warranted by their
      clinical condition.

PMID- 24746418
TI  - Chemical constituents and their antibacterial and antifungal activity from the
      Egyptian herbal medicine Chiliadenus montanus.
AB  - Phytochemical investigations of the CH2Cl2/MeOH (1:1) extract of air-dried aerial
      parts of Chiliadenus montanus afforded eight metabolites, in addition to eight
      other previously reported compounds, of which two were isolated for the first
      time as free acids. Structures were established by spectroscopic methods,
      including HREIMS, (1)H, (13)C, DEPT, (1)H-(1)H COSY, HMQC and HMBC NMR analysis.
      Antimicrobial activity against an array of common bacterial and fungal strains
      was measured via a colorimetric assay with minimal growth inhibition observed in
      the MUg/mL range for one of the tested metabolites. 

PMID- 24746419
TI  - Stepwise recruitment of transcellular and paracellular pathways underlies blood
      brain barrier breakdown in stroke.
AB  - Brain endothelial cells form a paracellular and transcellular barrier to many
      blood-borne solutes via tight junctions (TJs) and scarce endocytotic vesicles.
      The blood-brain barrier (BBB) plays a pivotal role in the healthy and diseased
      CNS. BBB damage after ischemic stroke contributes to increased mortality, yet the
      contributions of paracellular and transcellular mechanisms to this process in
      vivo are unknown. We have created a transgenic mouse strain whose endothelial TJs
      are labeled with eGFP and have imaged dynamic TJ changes and fluorescent tracer
      leakage across the BBB in vivo, using two-photon microscopy in the t-MCAO stroke
      model. Although barrier function is impaired as early as 6 hr after stroke, TJs
      display profound structural defects only after 2 days. Conversely, the number of
      endothelial caveolae and transcytosis rate increase as early as 6 hr after
      stroke. Therefore, stepwise impairment of transcellular followed by paracellular
      barrier mechanisms accounts for the BBB deficits in stroke.

PMID- 24746420
TI  - Slow and fast gamma rhythms coordinate different spatial coding modes in
      hippocampal place cells.
AB  - Previous work has hinted that prospective and retrospective coding modes exist in
      hippocampus. Prospective coding is believed to reflect memory retrieval
      processes, whereas retrospective coding is thought to be important for memory
      encoding. Here, we show in rats that separate prospective and retrospective modes
      exist in hippocampal subfield CA1 and that slow and fast gamma rhythms
      differentially coordinate place cells during the two modes. Slow gamma power and
      phase locking of spikes increased during prospective coding; fast gamma power and
      phase locking increased during retrospective coding. Additionally, slow gamma
      spikes occurred earlier in place fields than fast gamma spikes, and cell
      ensembles retrieved upcoming positions during slow gamma and encoded past
      positions during fast gamma. These results imply that alternating slow and fast
      gamma states allow the hippocampus to switch between prospective and
      retrospective modes, possibly to prevent interference between memory retrieval
      and encoding. 

PMID- 24746421
TI  - [Place of vulvovaginal candidiasis in the lower genital tract infections and
      associated risk factors among women in Benin].
AB  - OBJECTIVE: Determine the place of vulvo-vaginal candidiasis (VVC) in the lower
      genital infections and seek risk factors among women in Benin. PATIENTS AND
      METHODS: The study was conducted in the laboratory of mycology of Hopital de la
      Mere et de l'Enfant Lagune (Homel) from 1st March to 31st July, 2013. It involved
      all the women who were asked a vaginal swab and gave their consent in written
      form. After administration of a questionnaire, the vaginal samples were collected
      with sterile cotton swabs for a test with potassium hydroxide, an estimation of
      vaginal pH, direct microscopic examination, fresh, and after a Gram stain and
      culture on Sabouraud-chloramphenicol, ordinary agar and fresh blood agar.
      RESULTS: One hundred and thirty-one women were included in the study period.
      Clinical signs were dominated by vaginal discharge (74.8%), followed by vulvar
      pruritus (51.9%) and dyspareunia (36.6%). Culture on Sabouraud was positive in 51
      cases or 38.9%. Candida albicans was isolated in 96.1% of cases, against 3.9% of
      Candida glabrata. The risk factors involved were: pregnancy, antibiotics,
      synthetic underclothing and frequent wearing tight pants. In addition of Candida,
      Gardnerella vaginalis was found in 36.6% of samples with an association with C.
      albicans in 28.2% of cases. CONCLUSION: This study showed that vulvovaginal
      candidiasis is the leading cause of lower genital tract infections in women in
      Benin with involvement of several risk factors which research is needed to
      develop appropriate preventive measures.

PMID- 24746423
TI  - Images in emergency medicine. Man with severe shoulder pain. Gonococcal arthritis
      of the shoulder.

PMID- 24746422
TI  - Involvement of calcitonin gene-related peptide and receptor component protein in
      experimental autoimmune encephalomyelitis.
AB  - Calcitonin Gene-Related Peptide (CGRP) inhibits microglia inflammatory activation
      in vitro. We here analyzed the involvement of CGRP and Receptor Component Protein
      (RCP) in experimental autoimmune encephalomyelitis (EAE). Alpha-CGRP deficiency
      increased EAE scores which followed the scale alpha-CGRP null>heterozygote>wild
      type. In wild type mice, CGRP delivery into the cerebrospinal fluid (CSF) 1)
      reduced chronic EAE (C-EAE) signs, 2) inhibited microglia activation (revealed by
      quantitative shape analysis), and 3) did not alter GFAP expression, cell density,
      lymphocyte infiltration, and peripheral lymphocyte production of IFN-gamma, TNF
      alpha, IL-17, IL-2, and IL-4. RCP (probe for receptor involvement) was expressed
      in white matter microglia, astrocytes, oligodendrocytes, and vascular-endothelial
      cells: in EAE, also in infiltrating lymphocytes. In relapsing-remitting EAE (R
      EAE) RCP increased during relapse, without correlation with lymphocyte density.
      RCP nuclear localization (stimulated by CGRP in vitro) was I) increased in
      microglia and decreased in astrocytes (R-EAE), and II) increased in microglia by
      CGRP CSF delivery (C-EAE). Calcitonin like receptor was rarely localized in
      nuclei of control and relapse mice. CGRP increased in motoneurons. In conclusion,
      CGRP can inhibit microglia activation in vivo in EAE. CGRP and its receptor may
      represent novel protective factors in EAE, apparently acting through the
      differential cell-specific intracellular translocation of RCP. 

PMID- 24746424
TI  - Appropriate and safe utilization of helicopter emergency medical services. Policy
      statement.

PMID- 24746425
TI  - RDMS ultrasound certification for emergency physicians.

PMID- 24746426
TI  - RDMS certification for emergency physicians.

PMID- 24746427
TI  - Infectious Disease/CDC Update. Evaluation of hepatitis C virus infection testing
      and report-eight US sites, 2005-2011.

PMID- 24746428
TI  - American Board of Emergency Medicine report on residency training information
      (2013-2014), American Board of Emergency Medicine.
AB  - The American Board of Emergency Medicine gathers extensive background information
      on emergency medicine residency programs and the residents in them. We present
      the 2014 annual report on the status of US emergency medicine training programs. 

PMID- 24746429
TI  - Change of shift. Heads you live, tails you don't.

PMID- 24746430
TI  - Annals of Emergency Medicine Journal Club. Speed does matter: police transport of
      critical trauma victims: May 2014 Annals of Emergency Medicine Journal Club.

PMID- 24746431
TI  - Images in emergency medicine. Female with lower abdominal pain and bleeding.
      Abdominal ectopic pregnancy.

PMID- 24746432
TI  - Urinary infection in male patients with acute nephrolithiasis: should we hunt for
      a rare bird? In reply.

PMID- 24746433
TI  - Urinary infection in male patients with acute nephrolithiasis: should we hunt for
      a rare bird?

PMID- 24746434
TI  - The tragedy of adaptability beyond technology. In reply.

PMID- 24746435
TI  - The tragedy of adaptability beyond technology.

PMID- 24746436
TI  - Optimal older adult emergency care: Introducing multidisciplinary geriatric
      emergency department guidelines from the American College of Emergency
      Physicians, American Geriatrics Society, Emergency Nurses Association, and
      Society for Academic Emergency Medicine.

PMID- 24746437
TI  - Geriatric emergency department guidelines.

PMID- 24746438
TI  - Association of dietary factors with insulin resistance and inflammatory markers
      in subjects with diabetes mellitus and coronary artery disease in Indian
      population.
AB  - BACKGROUND: Insulin resistance (IR) and inflammation have been implicated in
      pathogenesis of diabetes and cardiovascular disease. Dietary factors have been
      reported to be associated to insulin resistance and inflammation. Hence, we
      studied the association of dietary factors with IR and inflammation in known
      patients with diabetes mellitus and coronary artery disease with the hypothesis
      that carbohydrate and fat will be positively; and protein, fiber and mineral will
      be negatively associated with IR and inflammatory markers. METHODS: Three hundred
      patients (M: 216; F: 84, age: 25-92) who had coronary disease on angiography were
      included in this study consecutively. All patients were evaluated for
      anthropometry and cardiovascular risk factors, and blood samples were collected
      for biochemical and inflammatory markers. Nutrition assessment was done once at
      the time of recruitment, based on 24h dietary recall. RESULTS AND CONCLUSIONS:
      Diabetic patients had significantly lower protein and total dietary fiber intake
      as compared to non diabetics. Diabetic patients had lower intake of vitamin A,
      riboflavin and vitamin B12. There was significantly lower intake of minerals by
      diabetic patients. Dietary carbohydrate and fat were positively, and protein and
      dietary fiber intakes were negatively correlated with HOMA-IR and IL-6. There was
      no correlation of individual amino acids with HOMA-IR but showed strong negative
      correlation with inflammatory markers (hsCRP; IL-6 and TNF-alpha). Intake of
      vitamins and minerals was negatively correlated with HOMA-IR and inflammatory
      markers. There is a strong correlation between dietary factors, insulin
      resistance and inflammatory markers.

PMID- 24746439
TI  - The risk factors associated with ultrasonic tissue characterization of carotid
      plaque in type 2 diabetic patients.
AB  - AIMS: Little is known about the related factors of plaque echogenicity in
      diabetic subjects. METHODS: This was a single-center, retrospective, study
      investigating a subgroup of patients of a previously published trial. We enrolled
      179 middle-aged and older Japanese type 2 diabetic patients with carotid plaque,
      and examined the parameters related with echogenicity of carotid plaque evaluated
      by gray-scale median (GSM). RESULTS: Proportion of males and body mass index
      (BMI) were significantly higher and HDL-cholesterol was significantly lower in
      the patients with low GSM (< 48) plaques (n = 89) as compared to those without it
      (n = 90). A multiple logistic regression analysis with gender, BMI, and HDL
      cholesterol as independent variables and the presence of low GSM plaques as an
      objective variable showed that male (odds ratio (OR) 2.36, 95%CI 1.05-5.31, p =
      0.037) and BMI (OR 1.12 [1.01-1.24], p = 0.029) were independently associated
      with low GSM plaques. Another multiple logistic regression analysis with gender,
      BMI, and low-HDL-cholesterolemia (HDL-C < 40 mg/dl) as independent variables
      showed that low-HDL-cholesterolemia (OR 2.30 [1.03-5.13], p = 0.042) and BMI (OR
      1.11 [1.00-1.22], p = 0.046) were independently associated with low GSM plaques.
      CONCLUSIONS: Our study suggests that gender, BMI and low-HDL-cholesterol are
      important determinants of the content of the vascular wall in diabetic subjects.

PMID- 24746440
TI  - Increased oxidation-related glutathionylation and carbonic anhydrase activity in
      endometriosis.
AB  - This study examined the possible involvement of carbonic anhydrase activation in
      response to an endometriosis-related increase in oxidative stress. Peripheral
      blood samples obtained from 27 healthy controls and 30 endometriosis patients,
      classified as having endometriosis by histological examination of surgical
      specimens, were analysed by multiple immunoassay and carbonic anhydrase activity
      assay. Red blood cells (RBC) were analysed for glutathionylated protein (GSSP)
      content in the membrane, total glutathione (GSH) in the cytosol and carbonic
      anhydrase concentration and activity. In association with a membrane increase of
      GSSP and a cytosolic decrease of GSH content in endometriosis patients, carbonic
      anhydrase significantly increased (P < 0.0001) both monomerization and activity
      compared with controls. This oxidation-induced activation of carbonic anhydrase
      was positively and significantly correlated with the GSH content of RBC (r =
      0.9735, P < 0.001) and with the amount of the 30-kDa monomer of carbonic
      anhydrase (r = 0.9750, P < 0.001). Because carbonic anhydrase activation is
      implied in many physiological and biochemical processes linked to pathologies
      such as glaucoma, hypertension, obesity and infections, carbonic anhydrase
      activity should be closely monitored in endometriosis. These data open promising
      working perspectives for diagnosis and treatment of endometriosis and hopefully
      of other oxidative stress-related diseases. Endometriosis is a chronic disease
      associated with infertility and local inflammatory response, which is thought to
      spread rapidly throughout the body as a systemic subclinical inflammation. One of
      the causes in the pathogenesis/evolution of endometriosis is oxidative stress,
      which occurs when reactive oxygen species are produced faster than the endogenous
      antioxidant defence systems can neutralize them. Once produced, reactive oxygen
      species can alter the morphological and functional properties of endothelial
      cells, including permeability and adhesion molecule expression, thus contributing
      to ongoing inflammation. Due to their main cellular functions--delivery of O2
      from lung to tissue and removal of CO2 from tissue to lung--red blood cells (RBC)
      are exposed to oxidative stress. Carbon dioxide in tissue capillaries diffuses
      into red cells, where it is rapidly hydrated by the action of cytosolic carbonic
      anhydrase. Analysis of the oxidation status of endometriotic RBC membranes showed
      a high content of glutathionylated proteins, indicating pre-existing oxidation
      related alterations. The increase in glutathionylated proteins was correlated to
      increased carbonic anhydrase activity in endometriotic RBC compared with healthy
      controls. Carbonic anhydrase is a family of metalloenzymes involved in many
      physiological processes such as acid-base homeostasis, respiration, carbon
      dioxide and ion transport, and bone resorption, and in the regulation of
      ureagenesis, gluconeogenesis, lipogenesis and tumourigenesis. Due to the
      potential implication of carbonic anhydrase activation in many pathologies, such
      as glaucoma, hypertension, obesity and infections, carbonic anhydrase activity
      should be closely monitored in endometriosis to prevent possible complications
      and/or worsening of related conditions.

PMID- 24746441
TI  - A prospective study of surgical procedures for patients with oligometastatic non
      small cell lung cancer.
AB  - BACKGROUND: Purely localized, oligometastatic, and widely metastatic tumors are
      likely to require different therapeutic strategies. Although surgical procedures
      for isolated pulmonary, brain, or adrenal metastases from lung cancer have been
      extensively evaluated, most data are from retrospective studies; accordingly, we
      conducted a prospective multicenter trial. METHODS: Patients were eligible if
      they had previously untreated clinical T1-2N0-1 lung cancer with single-organ
      metastasis, or single-organ metachronous metastasis after complete resection of
      pathologic T1-2N0-1 lung cancer. Metastatic lesions were classified into three
      groups: group A included metastasis in single organs other than brain or lung;
      group B included synchronous brain metastasis; and group C included pulmonary
      metastasis. The treatment intervention was surgical resection of metachronous
      metastasis or of both synchronous metastasis and primary lung cancer. RESULTS:
      From December 2002 through June 2011, 36 patients were enrolled. Two patients
      were ineligible, and the remaining 34 were analyzed; 6 (18%) had a benign lesion
      and no metastasis, 5 patients (15%) underwent incomplete resection of primary
      lung cancer, and 20 patients (59%) underwent complete resection of both primary
      lung cancer and metastasis. The 5-year survival rate for these 20 cases was
      44.7%. CONCLUSIONS: Clinical T1-2N0-1 lung cancer with a single-organ metastatic
      lesion was a good candidate for surgical resection. A 5-year survival rate of
      about 40% can be expected, which could be comparable with that for stage II non
      small cell lung cancer.

PMID- 24746442
TI  - Complexities of lysophospholipid signalling in glioblastoma.
AB  - Glioblastoma multiforme (GBM) is the most malignant brain tumour and continues to
      have a very poor median survival of 12-16 months despite current best therapies.
      These aggressive tumours always recur after treatment and are defined by their
      ability to diffusely infiltrate and invade normal brain parenchyma. Autotaxin is
      overexpressed in GBM, and is a potent chemotactic enzyme that produces
      lysophosphatidic acid. Lysophospholipid (LPL) signalling is known to increase
      invasion of solid tumours and is also dysregulated in GBM. The LPL pathway has
      been shown to interact with known cancer-related signalling pathways, including
      those for epidermal growth factor and yes-associated protein, which are also
      dysregulated in GBM. The interactions between these pathways provide insights
      into the complexities of cancer signalling and suggest potential novel targets
      for GBM.

PMID- 24746443
TI  - Onyx HD-500 embolization of intracranial aneurysms: modified technique using
      continuous balloon inflation under conscious sedation.
AB  - The conventional technique of intracranial aneurysm embolization using Onyx HD
      500 (ev3 Neurovascular, Irvine, CA, USA) involves repetitive balloon inflation
      deflation cycles under general anesthesia. By limiting parent artery occlusion to
      5 minutes, this cyclic technique is thought to minimize cerebral ischemia.
      However, intermittent balloon deflation may lengthen procedure time and allow
      balloon migration, resulting in intimal injury or Onyx leakage. We report our
      experience using a modified technique of uninterrupted Onyx injection with
      continuous balloon occlusion under conscious sedation. All Onyx embolization
      procedures for unruptured aneurysms performed by the senior author (A.J.R.)
      between September 2008 and April 2010 were retrospectively reviewed. Demographic,
      clinical, angiographic, and procedural data were recorded. Twenty-four
      embolization procedures were performed in 21 patients with 23 aneurysms,
      including four recurrences. Twenty aneurysms (87%) involved the paraclinoid or
      proximal supraclinoid internal carotid artery. Size ranged from 2.5 to 24mm and
      neck diameter from 2 to 8mm. The modified technique was employed in 19 cases. All
      but one patient (94.4%) tolerated continuous balloon inflation. Complete
      occlusion was achieved in 20 aneurysms (83.3%) and subtotal occlusion in three
      (12.5%). Stable angiographic results were seen in 85%, 94%, 94%, and 100% of
      patients at 6, 12, 24, and 36months, respectively. There were no deaths.
      Permanent non-disabling neurological morbidity occurred in one patient (4.2%).
      Minor, transient, and/or angiographic complications were seen in three patients
      (12.5%), none related to the technique itself. Onyx embolization of unruptured
      intracranial aneurysms can be safely and effectively performed using continuous
      balloon inflation under conscious sedation.

PMID- 24746444
TI  - [Objective evaluation of applying eye drops by elderly patients].
AB  - OBJECTIVE: To objectively evaluate the ability and skills of patients older than
      65 years to successfully administer a topical ocular eye drop. METHODS: A
      prospective study was conducted on a group of 25 patients with a diagnosis of dry
      eye or glaucoma, undergoing daily treatment with eye drops for at least one year.
      The procedure was recorded with a video camera at the time of the application.
      RESULTS: Of the total, 64% were diagnosed with glaucoma and 36% with dry eye.
      Almost half (44%) needed a single attempt to apply the drop, and 56% required 2
      attempts. In terms of the number of eye drops applied, 52% managed with a single
      drop, 16% 2 drops, a 12% 3 drops, and 20% 4 or more eye drops. Areas where the
      eye drop was deposited in the first attempt was, 32% into the conjunctival sac,
      32% on the outer corner of the eye, 8% in the inner angle, 8% in the nose, 12% on
      the cheek, 8% in other areas. CONCLUSIONS: Self-administration of eye drops by
      the elderly is a complex activity that can have an effect on the expected
      results.

PMID- 24746445
TI  - A new identified complication of intracystic hemorrhage in a large pineal gland
      cyst.
AB  - Pineal gland cysts are typically asymptomatic, benign cysts most commonly found
      incidentally in adults. In rare cases, a large pineal gland cyst can be
      complicated by intracystic hemorrhage, which could then manifest with
      neurological symptoms. We report a new complication of intracystic hemorrhage in
      a large pineal gland cyst in a 40-year-old man with new onset seizures. 

PMID- 24746447
TI  - Forefoot: a basic integrated imaging perspective for radiologists.
AB  - Imaging of the forefoot is increasingly requested for patients with
      metatarsalgia. Awareness with specific anatomic arrangements exclusive for the
      forefoot and widely variable pathologic entities associated with metatarsalgia
      helps the radiologist to tailor a cost-effective imaging approach. This will
      enable reaching a specific diagnosis as much as possible with subsequent proper
      patient management. This pictorial review aims to provide basic understanding for
      the different imaging modalities used in studying the forefoot. After that,
      certain anatomic arrangements exclusive for the forefoot are discussed. The final
      section of this review describes the imaging findings of some common forefoot
      problems. 

PMID- 24746446
TI  - Thyroid nodules with suspicious ultrasound findings: the role of ultrasound
      guided core needle biopsy.
AB  - The aim of this study was to evaluate the value of core needle biopsy (CNB) in
      the diagnosis of sonographically suspicious thyroid nodules. We retrospectively
      reviewed 997 patients with sonographically suspicious thyroid nodules who
      underwent CNB using pathological results as gold standard. In our result, the
      accuracy of CNB was 98.0%, and its area under the receiver operating
      characteristic curve was 0.981. The inconclusive result was in 22 (6.0%) of CNBs.
      Therefore, CNB demonstrates high rates of conclusive and accurate diagnosis in
      sonographically suspicious thyroid nodules, which may reduce repeat fine needle
      aspiration, diagnostic surgery, and unnecessary follow-up. 

PMID- 24746448
TI  - The influence of neuropathology on brain inflammation in human and experimental
      temporal lobe epilepsy.
AB  - It is unclear to what extent neuropathological changes contribute to brain
      inflammation observed in temporal lobe epilepsy (TLE). Here, we compared cytokine
      levels between histopathologically-confirmed sclerotic hippocampi and
      histopathologically-confirmed normal hippocampi from TLE patients. We analyzed a
      similar cytokine panel in the hippocampi of amygdala-kindled rats and we
      evaluated neuropathological changes by immunohistochemistry. In TLE patients,
      cytokine levels were not significantly different between sclerotic and non
      sclerotic hippocampi. Though kindling resulted in increased astrocyte activation,
      cytokine levels and microglia activation were unchanged. These results suggest
      that the chronic epileptic state in TLE can also occur in the absence of
      intracerebral inflammation. Highlights. 

PMID- 24746449
TI  - Bovine neonatal pancytopenia (BNP): novel insights into the incidence,
      vaccination-associated epidemiological factors and a potential genetic
      predisposition for clinical and subclinical cases.
AB  - Bovine neonatal pancytopenia (BNP) is a haemorrhagic disease of newborn calves
      elicited by colostrum from specific cows. Two studies have indicated that BNP
      inducing colostrum might be associated with alloantibodies directed against MHC
      class I in response to vaccination with a distinct inactivated viral vaccine.
      However, the proportion of alloantibody-producing individuals by far exceeds the
      proportion of clinical BNP cases in the vaccinated population. This raises the
      question about the incidence of subclinical, unrecognised cases and also suggests
      further factors involved in BNP pathogenesis, e.g., genetic predisposition. Our
      results on neonatal calves from a closely monitored resource population confirmed
      the hypothesis of a genetic predisposition for clinical BNP and suggest that the
      predisposition is also involved in subclinical BNP-cases. No indication was
      obtained for a higher frequency of subclinical BNP-cases compared with clinical
      cases. Neither time point nor frequency of vaccination was a relevant factor for
      BNP in our resource population.

PMID- 24746450
TI  - A peptide derived from the rotavirus outer capsid protein VP7 permeabilizes
      artificial membranes.
AB  - Biological membranes represent a physical barrier that most viruses have to cross
      for replication. While enveloped viruses cross membranes through a well
      characterized membrane fusion mechanism, non-enveloped viruses, such as
      rotaviruses, require the destabilization of the host cell membrane by processes
      that are still poorly understood. We have identified, in the C-terminal region of
      the rotavirus glycoprotein VP7, a peptide that was predicted to contain a
      membrane domain and to fold into an amphipathic alpha-helix. Its structure was
      confirmed by circular dichroism in media mimicking the hydrophobic environment of
      the membrane at both acidic and neutral pHs. The helical folding of the peptide
      was corroborated by ATR-FTIR spectroscopy, which suggested a transmembrane
      orientation of the peptide. The interaction of this peptide with artificial
      membranes and its affinity were assessed by plasmon waveguide resonance. We have
      found that the peptide was able to insert into membranes and permeabilize them
      while the native protein VP7 did not. Finally, NMR studies revealed that in a
      hydrophobic environment, this helix has amphipathic properties characteristic of
      membrane-perforating peptides. Surprisingly, its structure varies from that of
      its counterpart in the structure of the native protein VP7, as was determined by
      X-ray. All together, our results show that a peptide released from VP7 is capable
      of changing its conformation and destabilizing artificial membranes. Such
      peptides could play an important role by facilitating membrane crossing by non
      enveloped viruses during cell infection. 

PMID- 24746451
TI  - Unusual penetration of phospholipid mono- and bilayers by Quillaja bark saponin
      biosurfactant.
AB  - The interactions between a model phospholipid 1,2-dipalmitoyl-sn-glycero-3
      phosphocholine (DPPC) and a biosurfactant Quillaja Bark Saponin (QBS) obtained
      from the bark of Quillaja saponaria Molina were studied using simple models of
      biological membranes. QBS is known to interact strongly with the latter, exerting
      a number of haemolytic, cytotoxic and anti-microbial actions. The interaction of
      QBS dissolved in the subphase with DPPC monolayers and silicon-supported bilayers
      was studied above the cmc (10(-3)M). Surface pressure relaxation and surface
      dilatational rheology combined with quartz crystal microbalance (QCM) and neutron
      reflectivity (NR) were employed for this purpose. The DPPC-penetrating abilities
      of QBS are compared with those of typical synthetic surfactants (SDS, CTAB and
      Triton X-100). We show that the penetration studies using high surface activity
      (bio)surfactants should be performed by a subphase exchange, not by spreading
      onto the surfactant solution. In contrast to the synthetic surfactants of similar
      surface activity, QBS does not collapse DPPC mono- and bilayers, but penetrates
      them, improving their surface dilatational elastic properties even in the highly
      compressed solid state. The dilatational viscoelasticity modulus increases from
      204 mN/m for pure DPPC up to 310 mN/m for the QBS-penetrated layers, while it
      drops to near zero values in the case of the synthetic surfactants. The estimated
      maximum insertion pressure of QBS into DPPC monolayers exceeds the maximum
      surface pressure achievable in our setup, in agreement with the surface
      rheological response of the penetrated layers. 

PMID- 24746452
TI  - Vascular mortality in participants of a bipolar genomics study.
AB  - BACKGROUND: In prior work, we identified a relationship between symptom burden
      and vascular outcomes in bipolar disorder. OBJECTIVE: We sought to replicate
      these findings using a readily accessible measure of mood disorder chronicity and
      vascular mortality. METHODS: We conducted a mortality assessment using the
      National Death Index for 1716 participants with bipolar I disorder from the
      National Institute of Mental Health Genetics Initiative Bipolar Disorder
      Consortium. We assessed the relationship between the duration of the most severe
      depressive and manic episodes and time to vascular mortality (cardiovascular or
      cerebrovascular) using Cox proportional hazards models, adjusting for potentially
      confounding variables. RESULTS: Mortality was assessed a mean for 7 years
      following study intake, at which time 58 participants died, 18 of vascular
      causes. These participants had depression for much longer than their counterparts
      did (Wilcoxon rank sum Z = 2.30, p = 0.02) and the duration of the longest
      depressive episode in years was significantly associated with time to vascular
      mortality in models (hazard ratio = 1.16, 95% confidence interval: 1.02-1.33, p =
      0.02), which controlled for age, gender, vascular disease equivalents, and
      vascular disease risk factors. The duration of longest mania was not related to
      vascular mortality. CONCLUSION: The duration of the most severe depression is
      independently predictive of vascular mortality, lending further support to the
      idea that mood disorders hasten vascular mortality in a dose-dependent fashion.
      Further study of the relevant mechanisms by which mood disorders may hasten
      vascular disease and of integrated treatments for mood and cardiovascular risk
      factors is warranted.

PMID- 24746453
TI  - [Radiotherapy as conservative therapy for sarcomas within the irradiated field].
AB  - PURPOSE: To describe long-term outcome after combined-modality treatment
      including radiation therapy in patients with localized sarcoma within irradiated
      field. PATIENTS AND METHODS: Individual clinical data from all consecutive
      patients diagnosed and treated for a localized sarcoma within irradiated field
      between January 2000 and October 2011 at the Institut Claudius-Regaud, Toulouse,
      France, were retrospectively reviewed. RESULTS: Twenty-seven patients were
      eligible for this study. Ten patients were re-irradiated with a rate of
      unresectable, gross or microscopically positive margins disease significantly
      higher than the rest of the cohort (90% vs. 12%; P<0.001). After a median follow
      up of 3.8 years, there is a non-significant trend toward longer 4-year relapse
      free survival in the subgroup of patients who received adjuvant or definitive
      radiation therapy compared to the rest of the cohort (53% vs. 27%; P=0.09) with
      an acceptable toxicity profile allowing conservative management. CONCLUSION: The
      complete surgical resection sarcoma within irradiated field is often difficult to
      achieve enhancing the risk of relapse. Radiation therapy should be discussed when
      faced with an unresectable tumour or after suboptimal surgery as part of
      intensified local management with a curative intent.

PMID- 24746454
TI  - [Prostate-rectum spacers: optimization of prostate cancer irradiation].
AB  - In the curative radiotherapy of localized prostate cancer, improvements in
      biochemical control observed with dose escalation have been counterbalanced by an
      increase in radiation-induced toxicity. The injection of biodegradable spacers
      between prostate and rectum represents a new frontier in the optimization of
      radiotherapy treatments for patients with localized disease. Transperineal
      injection of different types of spacers under transrectal ultrasound guidance
      allows creating a 7-to-20 mm additional space between the prostate and the
      anterior rectal wall lasting 3 to 12 months. Dosimetrically, a relative reduction
      in the rectal volume receiving at least 70 Gy (V70) in the order of 43% to 84% is
      observed with all types of spacers, regardless of the radiotherapy technique
      used. Preliminary clinical results show for all spacers a good tolerance and a
      possible reduction in the acute side effects rate. The aim of the present
      systematic review of the literature is to report on indications as well as
      dosimetric and clinical advantages of the different types of prostate-rectum
      spacers commercially available (hydrogel, hyaluronic acid, collagen,
      biodegradable balloon).

PMID- 24746455
TI  - Evidence for genotype-phenotype correlation for OTOF mutations.
AB  - OBJECTIVES: The aim of this study is to evaluate the auditory phenotype in
      subjects with OTOF gene mutations to describe genotype-phenotype correlations.
      METHODS: Twenty-two affected members from three families with homozygous OTOF
      mutations were included. Nine subjects were evaluated audiologically with
      otoscopic examination, pure-tone audiometry, tympanometry with acoustic reflex
      testing, auditory brain stem responses, and otoacoustic emission tests. RESULTS:
      Homozygous c.4718T>C (p.Ile1573Thr) mutation was associated with the auditory
      neuropathy/auditory dys-synchrony (AN/AD) phenotype and with progressive
      sensorineural hearing loss in four siblings in one family, while homozygous
      c.4467dupC (p.I1490HfsX19) was associated with severe to profound sensorineural
      hearing loss without AN/AD in four relatives in another family. Homozygous
      c.1958delC (p.Pro653LeufsX13) mutation was associated with moderate sensorineural
      hearing loss without AN/AD in one affected person in an additional family.
      CONCLUSIONS: The audiological phenotype associated with different OTOF mutations
      appears to be consistently different suggesting the presence of a genotype
      phenotype correlation.

PMID- 24746456
TI  - Vitamin D levels and effects of vitamin D replacement in children with periodic
      fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) syndrome.
AB  - BACKGROUND: The periodic fever, aphthous stomatitis, pharyngitis and cervical
      adenitis (PFAPA) syndrome is an autoinflammatory disease characterized by
      regularly recurrent fever episodes due to seemingly unprovoked inflammation.
      OBJECTIVE: To assess serum 25-hydroxyvitamin D [25(OH)D] concentrations in
      children with PFAPA syndrome and evaluate longitudinally the effect of wintertime
      vitamin D supplementation on the disease course. STUDY DESIGN: We have evaluated
      25 Italian patients (19 males, 6 females, aged 2.4-5.3 years), fulfilling the
      Euro-Fever PFAPA criteria. For each patient, we recorded demographic and
      anthropometric data, clinical manifestations, serum calcium, phosphate, and
      25(OH)D. After 400 IU vitamin D supplementation during wintertime, clinical and
      auxological characteristics, calcium, phosphate, and 25(OH)D levels were re
      evaluated. Data were compared with a sex- and age-matched control group. RESULTS:
      PFAPA patients showed reduced 25(OH)D levels than controls (p<0.0001). Regarding
      the effect of seasons on vitamin D, winter 25(OH)D levels were significantly
      reduced than summer ones (p<0.005). Moreover, these levels were significantly
      lower than in healthy controls (p<0.005), and correlated with both fever episodes
      (p<0.005) and C-reactive protein values (p<0.005). After vitamin D
      supplementation, PFAPA patients showed a significantly decreased number of
      febrile episodes and modification of their characteristics (mean duration of
      fever episodes, p<0.05; number of febrile episodes per year p<0.005).
      CONCLUSIONS: Deficient and insufficient vitamin D serum levels were found in most
      children with PFAPA syndrome, and hypovitaminosis D might be a significant risk
      factor for PFAPA flares. However, vitamin D supplementation seems to
      significantly reduce the typical PFAPA episodes and their duration, supporting
      the role of vitamin D as an immune-regulatory factor in this syndrome.

PMID- 24746457
TI  - Benzimidazole derivative, BM601, a novel inhibitor of hepatitis B virus and HBsAg
      secretion.
AB  - Hepatitis B virus (HBV) belongs to the Hepadnaviridae family. HBsAg, greatly
      outnumbered mature virion, has been mysterious since the discovery of HBV. A
      novel benzimidazole derivative, BM601, is identified inhibiting the secretion of
      HBV virions and HBsAg, with 50% effective concentration of 0.6MUM and 1.5MUM, as
      well as 50% cytotoxicity concentration of 24.5MUM. It has no effect on
      transcription, protein production, nucleocapsid formation or intracellular HBV
      DNA synthesis. Immunofluorescence analysis suggests that BM601 might inhibit
      virion and HBsAg secretion by interfering surface protein aggregation in trans
      Golgi apparatus. Furthermore, BM601 does not trigger cellular stress response or
      affect HBeAg or host protein secretion. We hypothesize that BM601 is a secretion
      inhibitor functioning at the level of virion and HBsAg secretion pathway. 

PMID- 24746458
TI  - Induction of neutralizing antibodies to influenza A virus H7N9 by inactivated
      whole virus in mice and nonhuman primates.
AB  - We evaluated the immunogenicity of hemagglutinin (HA) in the context of
      inactivated H7N9/AH/1/13-PR8 whole-virion. At 4weeks after immunization with
      15MUg HA, mice produced hemagglutination inhibition (HI) titers of 1:192 and
      neutralizing antibodies of 1:317. Aluminum hydroxide (alum), or a booster
      immunization, or both increased HI to 1:768, 1:384, 1:896 and neutralizing
      antibodies to 1:1868, 1:2302, 1:10,000, respectively. Macaques generated HI of
      1:190 or 1:360 and virus neutralizing titers of 1:280 or 1:658 at 3weeks after
      immunization with HA alone or with alum. Sera from immunized mice and macaques
      protected mice from infection of A/Anhui/1/2013 (H7N9), suggesting an H7N9
      vaccine is immunologically feasible. 

PMID- 24746461
TI  - Editorial comment.

PMID- 24746459
TI  - E138A in HIV-1 reverse transcriptase is more common in subtype C than B:
      implications for rilpivirine use in resource-limited settings.
AB  - The nonnucleoside reverse transcriptase (RT) inhibitor rilpivirine (RPV) has been
      co-formulated with emtricitabine and tenofovir disoproxil fumarate for initial
      therapy of HIV-1-infected individuals. RPV, formulated as a long-acting
      nanosuspension, will also be assessed for its ability to prevent HIV-1 infection
      in resource limited settings. In this study, we determined whether any pre
      existing genetic differences occurred among different HIV-1 subtypes at residues
      in RT associated with decreased virologic response to RPV. We found that the
      E138A substitution occurs more frequently in subtype C (range: 5.9-7.5%) than B
      (range: 0-2.3%) sequences from both treatment-naive and -experienced individuals
      (p<0.01) in 4 independent genotype databases. In one of the databases (Stanford
      University), E138K and E138Q were also more common in RTI-experienced subtype C
      sequences (1.0% and 1.1%, respectively) than in subtype B sequences (0.3% and
      0.6%, respectively). E138A/K/Q in subtype C decreased RPV susceptibility 2.9-,
      5.8-, and 5.4-fold, respectively. Taken together, these data suggest that E138A
      could impact treatment or prevention strategies that include RPV in geographic
      areas where subtype C infection is prevalent. 

PMID- 24746462
TI  - Environment and Health in Children Day Care Centres (ENVIRH) - Study rationale
      and protocol.
AB  - BACKGROUND: Indoor air quality (IAQ) is considered an important determinant of
      human health. The association between exposure to volatile organic compounds,
      particulate matter, house dust mite, molds and bacteria in day care centers (DCC)
      is not completely clear. The aim of this project was to study these effects.
      METHODS - STUDY DESIGN: This study comprised two phases. Phase I included an
      evaluation of 45 DCCs (25 from Lisbon and 20 from Oporto, targeting 5161
      children). In this phase, building characteristics, indoor CO2 and air
      temperature/relative humidity, were assessed. A children's respiratory health
      questionnaire derived from the ISAAC (International Study on Asthma and Allergies
      in Children) was also distributed. Phase II encompassed two evaluations and
      included 20 DCCs selected from phase I after a cluster analysis (11 from Lisbon
      and 9 from Oporto, targeting 2287 children). In this phase, data on ventilation,
      IAQ, thermal comfort parameters, respiratory and allergic health, airway
      inflammation biomarkers, respiratory virus infection patterns and parental and
      child stress were collected. RESULTS: In Phase I, building characteristics,
      occupant behavior and ventilation surrogates were collected from all DCCs. The
      response rate of the questionnaire was 61.7% (3186 children). Phase II included
      1221 children. Association results between DCC characteristics, IAQ and health
      outcomes will be provided in order to support recommendations on IAQ and
      children's health. A building ventilation model will also be developed.
      DISCUSSION: This paper outlines methods that might be implemented by other
      investigators conducting studies on the association between respiratory health
      and indoor air quality at DCC.

PMID- 24746463
TI  - In vitro-in vivo activity relationship of substituted benzimidazole cell division
      inhibitors with activity against Mycobacterium tuberculosis.
AB  - Structure based drug design was used to develop a compound library of novel 2,5,6
      and 2,5,7-trisubstituted benzimidazoles. Three structural analogs, SB-P1G10, SB
      P8B2 and SB-P3G2 were selected from this library for advanced study. In vitro
      studies revealed that SB-P8B2 and SB-P3G2 had sigmoidal kill-curves while in
      contrast SB-P1G10 showed a narrow zonal susceptibility. The in vitro studies also
      demonstrated that exposure to SB-P8B2 or SB-P3G2 was bactericidal, while SB-P1G10
      treatment never resulted in complete killing. The dose curves for the three
      compounds against clinical isolates were comparable to their respective dose
      curves in the laboratory strain of Mycobacterium tuberculosis. SB-P8B2 and SB
      P3G2 exhibited antibacterial activity against non-replicating bacilli under low
      oxygen conditions. SB-P3G2 and SB-P1G10 were assessed in acute short-term animal
      models of tuberculosis, which showed that SB-P3G2 demonstrated activity against
      M. tuberculosis. Together, these studies reveal an in vitro-in vivo relationship
      of the 2,5,6-trisubstituted benzimidazoles that serves as a criterion for
      advancing this class of cell division inhibitors into more resource intensive in
      vivo efficacy models such as the long-term murine model of tuberculosis and Pre
      IND PK/PD studies. Specifically, these studies are the first demonstration of
      efficacy and an in vitro-in vivo activity relationship for 2,5,6-trisubstituted
      benzimidazoles. The in vivo activity presented in this manuscript substantiates
      this class of cell division inhibitors as having potency and efficacy against M.
      tuberculosis. 

PMID- 24746464
TI  - Identification of the stereochemical requirements in the 4-aryl-2
      cycloalkylidenhydrazinylthiazole scaffold for the design of selective human
      monoamine oxidase B inhibitors.
AB  - Exploring the effect that substituents on the cycloaliphatic ring had on the
      inhibitory activity against human monoamine oxidase B of a series of 4-aryl-2
      cycloalkylidenhydrazinylthiazoles led to the synthesis of a new series of 2
      methylcyclopentyl and 3-methylcyclopentyl derivatives which were tested in vitro
      as mixtures of diastereoisomers. In fact, due to the presence of a chiral center
      on the cycloaliphatic ring and a trisubstituted CN bond, they exist as four
      diastereoisomers ((E)-(R), (E)-(S), (Z)-(R), (Z)-(S)). 4-(2,4-Difluorophenyl)-2
      (2-(3-methylcyclopentylidene)hydrazinyl)thiazole was chosen as a model to
      investigate the influence of stereochemical requirements on the inhibitory
      activity against hMAO-B of these derivatives after a stereoconservative synthesis
      and semi-preparative HPLC diastereoseparation. (R)-(Z) isomer of this compound
      was endowed with a potent and selective hMAO-B inhibition higher than that of
      reference drugs as also corroborated by molecular modeling studies. 

PMID- 24746465
TI  - Carbonic anhydrase inhibitors. Inhibition of human cytosolic isoforms I and II
      with (reduced) Schiff's bases incorporating sulfonamide, carboxylate and
      carboxymethyl moieties.
AB  - A library of Schiff bases was synthesized by condensation of aromatic amines
      incorporating sulfonamide, carboxylic acid or carboxymethyl functionalities as
      Zn(2+)-binding groups, with aromatic aldehydes incorporating tert-butyl, hydroxy
      and/or methoxy groups. The corresponding amines were thereafter obtained by
      reduction of the imines. These compounds were assayed for the inhibition of two
      cytosolic human carbonic anhydrase (hCA, EC 4.2.1.1) isoenzymes, hCA I and II.
      The Ki values of the Schiff bases were in the range of 7.0-21,400nM against hCA
      II and of 52-8600nM against hCA I, respectively. The corresponding amines showed
      Ki values in the range of 8.6nM-5.3MUM against hCA II, and of 18.7-251nM against
      hCA I, respectively. Unlike the imines, the reduced Schiff bases are stable to
      hydrolysis and several low-nanomolar inhibitors were detected, most of them
      incorporating sulfonamide groups. Some carboxylates also showed interesting CA
      inhibitory properties. Such hydrosoluble derivatives may show pharmacologic
      applications. 

PMID- 24746466
TI  - Base substituted 5'-O-(N-isoleucyl)sulfamoyl nucleoside analogues as potential
      antibacterial agents.
AB  - Aminoacyl-sulfamoyl adenosines are well-known nanomolar inhibitors of the
      corresponding prokaryotic and eukaryotic tRNA synthetases in vitro. Inspired by
      the aryl-tetrazole containing compounds of Cubist Pharmaceuticals and the
      modified base as found in the natural antibiotic albomycin, the selectivity issue
      of the sulfamoylated adenosines prompted us to investigate the pharmacophoric
      importance of the adenine base. We therefore synthesized and evaluated several
      isoleucyl-sulfamoyl nucleoside analogues with either uracil, cytosine,
      hypoxanthine, guanine, 1,3-dideaza-adenine (benzimidazole) or 4-nitro
      benzimidazole as the heterocyclic base. Based on the structure and antibacterial
      activity of microcin C, we also prepared their hexapeptidyl conjugates in an
      effort to improve their uptake potential. We further compared their antibacterial
      activity with the parent isoleucyl-sulfamoyl adenosine (Ile-SA), both in in vitro
      and in cellular assays. Surprisingly, the strongest in vitro inhibition was found
      for the uracil containing analogue 16f. Unfortunately, only very weak growth
      inhibitory properties were found as of low uptake. The results are discussed in
      the light of previous literature findings. 

PMID- 24746467
TI  - Building the headlight: an illuminating experience.

PMID- 24746468
TI  - Online, social media and mobile technologies for psychosis treatment: a
      systematic review on novel user-led interventions.
AB  - BACKGROUND: Internet and mobile-based interventions provide a unique opportunity
      to deliver cost-effective, accessible, time-unlimited support to people with
      psychosis. The aims of this study were to systematically compile and analyze the
      evidence on the acceptability, feasibility, safety and benefits of online and
      mobile-based interventions for psychosis. METHODS: Systematic review of peer
      reviewed studies examining the usability, acceptability, feasibility, safety or
      efficacy of user-led, Internet or mobile-based interventions, with at least 80%
      of participants diagnosed with schizophrenia-spectrum disorders. RESULTS: Of 38
      potentially relevant articles, 12 were eligible for inclusion. Interventions
      included web-based psycho-education; web-based psycho-education plus moderated
      forums for patients and supporters; integrated web-based therapy, social
      networking and peer and expert moderation; web-based CBT; personalized advice
      based on clinical monitoring; and text messaging interventions. Results showed
      that 74-86% of patients used the web-based interventions efficiently, 75-92%
      perceived them as positive and useful, and 70-86% completed or were engaged with
      the interventions over the follow-up. Preliminary evidence indicated that online
      and mobile-based interventions show promise in improving positive psychotic
      symptoms, hospital admissions, socialization, social connectedness, depression
      and medication adherence. CONCLUSIONS: Internet and mobile-based interventions
      for psychosis seem to be acceptable and feasible and have the potential to
      improve clinical and social outcomes. The heterogeneity, poor quality and early
      state of current research precludes any definite conclusions. Future research
      should investigate the efficacy of online and mobile interventions through
      controlled, well-powered studies, which investigate intervention and patient
      factors associated with take-up and intervention effects.

PMID- 24746469
TI  - Flexible microRNA arm selection in rice.
AB  - MicroRNAs act at the post-transcriptional level and guide Argonaute proteins to
      cleave their corresponding target transcripts. However, little attention has been
      paid to arm selection in miRNA precursors. In this study, small RNA high
      throughput sequencing data from 29 different rice libraries were pooled to
      investigate tissue- and abiotic stress-specific dynamic expression of miRNAs. We
      found that more than half of pre-miRNAs showed changes in arm selection in
      different tissues and/or under different abiotic stresses. Our findings suggest
      that miRNA selection is remarkably prevalent in plants, providing new insights
      into the role of miRNAs in plant growth and development. 

PMID- 24746470
TI  - Systemic identification of estrogen-regulated genes in breast cancer cells
      through cap analysis of gene expression mapping.
AB  - To explore the estrogen-regulated genes genome-widely in breast cancer, cap
      analysis of gene expression (CAGE) sequencing was performed in MCF-7 cells under
      estrogen treatment. Estrogen-regulated expressional changes were found in 1537
      CAGE tag clusters (TCs) (?1.5 or ?0.66-folds). Among them, 15 TCs were situated
      in the vicinity of (?10 kb) reported estrogen receptor-binding sites. Knockdown
      experiments of the 15 TC-associated genes demonstrated that the genes such as
      RAMP3, ISOC1 and GPRC5C potentially regulate the growth or migration of MCF-7
      cells. These results suggest that CAGE sequencing will reveal novel estrogen
      target genes in breast cancer.

PMID- 24746471
TI  - Long-term low-dose alpha-particle enhanced the potential of malignant
      transformation in human bronchial epithelial cells through MAPK/Akt pathway.
AB  - Since the wide usage of ionizing radiation, the cancer risk of low dose radiation
      (LDR) (<0.1 Gy) has become attractive for a long time. However, most results are
      derived from epidemiologic studies on atomic-bomb survivors and nuclear accidents
      surrounding population, and the molecular mechanism of this risk is elusive. To
      explore the potential of a long-term LDR-induced malignant transformation, human
      bronchial epithelial cells Beas-2B were fractionally irradiated with 0.025 Gy
      alpha-particles for 8 times in total and then further cultured for 1-2 months. It
      was found that the cell proliferation, the abilities of adhesion and invasion,
      and the protein expressions of p-ERK, p-Akt, especially p-P38 were not only
      increased in the multiply-irradiated cells but also in their offspring 1-2 months
      after the final exposure, indicating high potentiality of cell malignant
      transformation. On opposite, the expressions of p-JNK and p-P66 were diminished
      in the subcultures of irradiated cells and thus may play a role of negative
      regulation in canceration. When the cells were transferred with p38 siRNA, the
      LDR-induced enhancements of cell adhesion and invasion were significantly
      reduced. These findings suggest that long-term LDR of alpha-particles could
      enhance the potential of malignant transformation incidence in human bronchial
      epithelial cells through MAPK/Akt pathway.

PMID- 24746472
TI  - TERT attenuated ER stress-induced cell death.
AB  - Tumor cells are frequently encountered in nutrient-deprived areas, though the
      mechanisms underlying their survival are unclear. In the present study, we found
      that depriving cells of glucose caused endoplasmic reticulum stress (ER stress)
      in a breast cancer cells line, MCF-7, and that specific activation of ER stress
      increased telomerase reverse transcriptase (TERT) expression. TERT expression
      would function in counteracting against the stress because over-expression of
      TERT diminished ER stress-induced cell death. Therefore, the results provide
      evidence for the underlying mechanisms of tumor progression in stressed
      conditions, highlighting that ER stress induces TERT expression to withstand
      environmental stress, a mechanism which we termed the "ER stress-TERT axis". 

PMID- 24746473
TI  - Environmental attitudes and political partisanship.
AB  - OBJECTIVE: To explore the impact of political partisanship on environmental
      attitudes related to climate change in United States and its implications for
      public health. STUDY DESIGN: An integrative literature review. METHODS: A
      literature review of English articles was performed from January 2013 to March
      2013 using the following databases: CINAHL, PubMed, Academic Search Premier,
      Business Source Premier, ERIC, psychINFO, and Wiley Online Library. Empirical and
      review articles and Internet sources were included. RESULTS: Continued mass
      emission of carbon dioxide and other greenhouse gases will exacerbate the
      consequences of global warming and climate change. As one of the key global
      contributors of carbon emissions, the lack of climate change policy and
      regulatory practices at the federal level in the United States is of great
      concern. Political partisanship in the US is largely to blame for this inaction,
      as efforts for drastic remediation action is met with rejection from conservative
      groups who do not believe that global warming and climate change are a problem,
      despite scientific evidence to the contrary. To promote the health of the entire
      population, there needs to be a paradigm shift from consumption driven economic
      growth as advocated by the Republicans to a realization of true prosperity beyond
      growth in order to create a sustainable world. CONCLUSION: This presents a
      critical challenge to public health professionals as political partisanship has
      the power to impact environmental attitudes and have serious implications for
      public health. Preserving the environment must take precedence over economic
      growth if we want a habitable planet low in carbon.

PMID- 24746474
TI  - Utility of local suicide data for informing local and national suicide prevention
      strategies.
AB  - OBJECTIVES: The practice of 'suicide audit' refers to the systematic collection
      of local data on suicides in order to learn lessons and inform suicide prevention
      plans. Little is known about the utility of this activity. The aim of this study
      was to ascertain from Directors of Public Health in England how they were
      conducting suicide audit and what resources they were investing in it; how the
      findings were being used, and how the process might be improved. STUDY DESIGN: E
      mail survey. METHODS: A questionnaire was sent to all 153 Primary Care Trusts
      (PCTs) in England prior to their dissolution in 2013. Simple descriptive
      statistics were performed in an Excel database. RESULTS: Responses were received
      from 49% of PCTs, of which 83% were conducting a regular audit of deaths by
      suicide. Many had worked hard to overcome procedural obstacles and were investing
      huge amounts of time and effort in collecting data, but it is not clear that the
      findings were being translated effectively into action. With few exceptions, PCTs
      were unable to demonstrate that the findings of local audits had influenced their
      suicide prevention plans. CONCLUSIONS: In the light of fresh calls for the
      practice of suicide audit to be made mandatory in England, these results are
      worrying. The study suggests that there is a pressing need for practical guidance
      on how the findings of local suicide audits can be put to use, and proposes a
      framework within which such guidance could be developed.

PMID- 24746475
TI  - Towards selective lysophospholipid GPCR modulators.
AB  - G-protein-coupled receptors (GPCRs) that recognize the lysophospholipids (LPLs)
      are grouped into two phylogenetically distinct families: the endothelial
      differentiation gene (Edg) and non-Edg GPCRs. Owing to their more recent
      identification, and hindered by a lack of selective pharmacological tools, our
      understanding of the functions and signaling pathways of the non-Edg GPCRs is
      still in its infancy. Targeting the non-conserved allosteric binding sites of the
      LPL GPCRs shows particular promise for the development of selective modulators by
      structure-based drug design. However, only one Edg GPCR (S1PR1) structure has
      been determined to date, and it has low sequence identity with the non-Edg GPCRs
      (<20%). Thus, a representative structure of a non-Edg GPCR remains a pressing
      objective for selective structure-based drug design. Obtaining selective
      modulators targeting the non-Edg receptors would help to unravel the biology
      behind these novel GPCRs and potentially will support therapeutic treatment of
      diseases such as cancer, inflammation, and neuropsychiatric disorders. 

PMID- 24746476
TI  - Acute ocular myositis occurring under etanercept for rheumatoid arthritis.
AB  - Ocular myositis is a rare disorder characterized by inflammation of single or
      multiple extra-ocular eye muscles presenting with painful diplopia and/or
      ophthalmoplegia. The etiology remains obscure and it is rarely associated with
      rheumatoid arthritis. We here reported the case of a 61-year-old woman treated by
      TNF-alpha blockade, namely etanercept, for rheumatoid arthritis for ten years who
      developed an acute ocular myositis. The patient improved after etanercept was
      stopped and initiation of high doses of corticosteroids. To our knowledge, this
      is the second report of ocular myositis occurring under TNF-alpha blockade
      treatment for rheumatoid arthritis.

PMID- 24746477
TI  - Sirt1 activity in peripheral blood mononuclear cells from patients with
      rheumatoid arthritis.

PMID- 24746478
TI  - Scaling of the viscoelastic shell properties of phospholipid encapsulated
      microbubbles with ultrasound frequency.
AB  - Phospholipid encapsulated microbubbles are widely employed as clinical diagnostic
      ultrasound contrast agents in the 1-5 MHz range, and are increasingly employed at
      higher ultrasound transmit frequencies. The stiffness and viscosity of the
      encapsulating "shells" have been shown to play a central role in determining both
      the linear and nonlinear response of microbubbles to ultrasound. At lower
      frequencies, recent studies have suggested that shell properties can be frequency
      dependent. At present, there is only limited knowledge of how the viscoelastic
      properties of phospholipid shells scale at higher frequencies. In this study,
      four batches of in-house phospholipid encapsulated microbubbles were fabricated
      with decreasing volume-weighted mean diameters of 3.20, 2.07, 1.82 and 1.61 MUm.
      Attenuation experiments were conducted in order to assess the frequency-dependent
      response of each batch, resulting in resonant peaks in response at 4.2, 8.9, 12.6
      and 19.5 MHz, respectively. With knowledge of the size measurements, the
      attenuation spectra were then fitted with a standard linearized bubble model in
      order to estimate the microbubble shell stiffness Sp and shell viscosity Sf,
      resulting in a slight increase in Sp (1.53-1.76 N/m) and a substantial decrease
      in Sf (0.29*10(-6)-0.08*10(-6) kg/s) with increasing frequency. These results
      performed on a single phospholipid agent show that frequency dependent shell
      properties persist at high frequencies (up to 19.5MHz).

PMID- 24746479
TI  - Diuretic and anti-diuretic activities of the ethanol and aqueous extracts of
      Alismatis rhizoma.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Alismatis rhizoma or Alisma orientale (Zexie in
      Chinese), the dried rhizome of Alisma orientale Juzepzuk (Alismataceae), is a
      well-known traditional Chinese medicine and is used as an agent for diuresis and
      for excreting dampness in Asia and Europe. In this paper, we report the diuretic
      activities of the ethanol extract (EE) and the aqueous extract (AE) of A. rhizoma
      (AR). MATERIALS AND METHODS: The EE and AE were orally administered to rats. The
      urinary excretion rate and pH, and electrolyte excretion were measured in the
      urine of saline-loaded rats. RESULTS: The results showed that EE could increase
      the urine output at 2.5, 5 and 10mg/kg doses but decrease the urine output at 20,
      40 and 80mg/kg doses compared with the control group. The 5 and 10mg/kg doses of
      EE increased the urine electrolyte excretion, but the effects on Na(+)/K(+)
      values were too weak to reach statistical significance. The Na(+) excretion and
      Cl(-) excretion were markedly decreased with the 20, 40 and 80mg/kg doses of EE,
      but the effect on K(+) excretion was notably slight. All of the tested doses of
      AE produced an increase in urinary excretion, but the increase did not reach
      statistical significance. CONCLUSIONS: This study identified that EE but not AE
      presents a notable diuretic effect, and EE had diuretic and anti-diuretic
      effects, which appears to be related to the sodium-chloride co-transporter in the
      renal distal convoluting tubule. This study demonstrated for the first time that
      the EE of AR has a dual effect on renal function, including promotion of diuretic
      activity at lower doses and inhibiting diuretic activity at higher doses, and the
      AR dose should be given more attention in clinical applications. This study will
      play a critical and guiding role in the dosing of AR as a diuretic drug in
      clinical applications.

PMID- 24746480
TI  - Ethnobotanical study of medicinal plants of Sirjan in Kerman Province, Iran.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: From ancient time human beings have used
      different plants, animals and minerals to prevent and treat various diseases. In
      this respect, plants have been of particular importance. Ethnobotany is the
      science of reviewing how indigenous people and local tribes have used their
      regional plants for particular purposes such as treating diseases in the past.
      The information gathered from such studies can help to improve national health
      systems and even lead to the discovery of new medicines. Keeping this in mind, in
      this study a survey of Sirjan area ethnobotany was conducted during 2011-2012.
      MATERIALS AND METHODS: At the beginning, thirteen local people were interviewed
      about their region's medicinal plants and their consumptions. These plants were
      collected and identified using identification keys. The data collected was
      analyzed using quantitative value indices FIC, RFC and CI. RESULT: Many plants
      collected have medicinal properties and have been used by local people to treat
      various ailments. Of these plants, nineteen families, 37 genera and 43 species
      belonged to medicinal plants. Among them, Lamiaceae with 8 species and Malva L.
      with 3 species were the largest medicinal plant families and genera,
      respectively. These plants are often used as decoction (28%) and as powder (21%).
      Also, the fruit of these plants are used most often. Besides being used as
      medicinal plants, they have other uses such as food, fuel, etc. Malva sylvestris
      has the largest value of relative frequency of citation and cultural importance
      indices. The most ailment categories have the highest level of informant
      agreement (mean FIC=0.92). CONCLUSION: Despite the semi-desert climate and lack
      of rich vegetation, many medicinal and economic plants are found in Sirjan
      region. Uncontrolled harvesting of the medicinal plants such as Bunium persicum,
      Cuminum cyminum, Zataria multiflora and Satureja bachtiarica in this region by
      local people has increased the risk of their extinction and calls for a restrict
      control over their protection by the authorities.

PMID- 24746481
TI  - The hepatoprotective effect and chemical constituents of total iridoids and
      xanthones extracted from Swertia mussotii Franch.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Total iridoids and xanthones (TIXS) were
      extracted from Swertia mussotii Franch, one of the most important eight Tibetan
      medicines in China, which was recorded in the book of Jingzhu Bencao and used for
      clinical treatment of cholestatic hepatitis for many years. Our aim was to study
      the hepatoprotective effect and chemical constituents of the TIXS. MATERIALS AND
      METHODS: Crude extracts were prepared using 90% ethanol, and individual fractions
      were collected following HPD-300 macroporous resin column chromatography. HPLC/MS
      was applied to qualitatively and quantitatively analyze the TIXS. Then, the alpha
      naphthylisot hiocyanate-induced liver damage model was used to assess the
      hepatoprotective effect of the TIXS. RESULTS: A total of 12 compounds were
      identified by the fingerprint chromatography of the TIXS, and swertiamarin and
      swertianolin were shown to be its two main components. Oral administration of the
      TIXS at a dose of 35, 70 or 140 mg kg(-1), swertiamarin at a dose of 20 mg kg(-1)
      or swertianolin at a dose of 20 mg kg(-1), for 7 days in mice significantly
      reduced the alpha-naphthylisot hiocyanate-induced levels of alanine
      aminotransferase, aspartate aminotransferase and the total and direct bilirubins,
      and increased the bile flow (P<0.01). CONCLUSION: These findings suggest that the
      TIXS exhibits significant hepatoprotective effect in the liver damage model
      induced by alpha-naphthylisot hiocyanate. Its active constituents include
      swertiamarin and swertianolin.

PMID- 24746482
TI  - Inhibition of myeloperoxidase activity by the alkaloids of Peganum harmala L.
      (Zygophyllaceae).
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Seeds and aerial parts of Peganum harmala L. are
      widely used in Algeria as anti-inflammatory remedies. Evaluation of Peganum
      harmala total alkaloids extracts and pure beta-carboline compounds as an anti
      inflammatory treatment by the inhibition of an enzyme key of inflammatory,
      myeloperoxidase (MPO) and HPLC quantification of the alkaloids from the different
      parts of plant. MATERIALS AND METHODS: MPO inhibition was tested using taurine
      chloramine test. The inhibition of LDL oxidation induced by MPO was carried out.
      The molecular docking analysis of Peganum harmala alkaloids on MPO was performed
      using the Glide XP docking protocol and scoring function and the redox potential
      of alkaloids was determined using an Epsilon potentiostat. The concentration of
      harmala alkaloids was determined using HPLC analysis. RESULTS: The HPLC profiling
      of the active total alkaloids indicates that beta-carboline e.g. harmine,
      harmaline, harmane, harmol and harmalol are major components. As beta-carbolines
      resemble tryptamine, of which derivatives are efficient inhibitors of MPO, the
      harmala alkaloids were tested for their activity on this enzyme. Total alkaloids
      of the seeds and of the aerial parts strongly inhibited MPO at 20ug/mL (97+/-5%
      and 43+/-4%, respectively) whereas, at the same concentration, those of the roots
      showed very low inhibition (15+/-6%). Harmine, harmaline and harmane demonstrated
      a significant inhibition of MPO at IC50 of 0.26, 0.08 and 0.72uM respectively.
      These alkaloids exerted a similar inhibition effects on MPO-induced LDL
      oxidation. Molecular docking analysis of Peganum harmala alkaloids on MPO showed
      that all active Peganum harmala alkaloids have a high affinity on the active site
      of MPO (predicted free energies of binding up to -3.1kcal/mol). Measurement of
      redox potentials versus the normal hydrogen electrode clearly differentiated (i)
      the high MPO inhibitory activity of harmine, harmaline and harmane (+1014, 1014
      and 1003mV, respectively); and (ii) the low activity of harmalol and harmol
      (+629/778 and 532/644mV, respectively). A reverse phase HPLC method has been
      developed to determine simultaneously five alkaloids of Peganum harmala. Seeds
      contained all five beta-carboline derivatives with the main active alkaloids,
      harmaline and harmine, being up to 3.8% and 2.9%, respectively. Up to 3.2% of
      harmine was determined in the roots. The four beta-carboline derivatives,
      harmine, harmaline, harmane and harmalol were identified in the aerial parts. The
      highest inhibitory effect observed in seeds and the moderate effect of aerial
      parts could be explained by their harmine and harmaline content. In contrast, the
      very weak inhibition of the root extract, despite the presence of harmine, may
      tentatively be explained by the high concentration of harmol which can reduce
      Compound II of MPO to the native form. CONCLUSION: The inhibition of MPO by
      Peganum harmala beta-carboline alkaloids, herein reported for the first time, may
      explain the anti-inflammatory effect traditionally attributed to its herbal
      medicine.

PMID- 24746483
TI  - The effect of Lycium barbarum polysaccharides on the male rats' reproductive
      system and spermatogenic cell apoptosis exposed to low-dose ionizing irradiation.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Lycium barbarum, a Solanaceous defoliated
      shrubbery, has been used as a kind of traditional Chinese herbal medicines for
      thousands of years. Lycium barbarum polysaccharide (LBP) is the main bioactive
      component of Lycium barbarum. The aim of this study was to investigate the
      radioresistant effect of LBP on the damage of male rats' reproductive system and
      spermatogenic cells caused by low-dose (60)Co-gamma irradiation. MATERIALS AND
      METHODS: Male rats were randomly divided into 7 groups and treated with
      irradiation and/or LBP: normal control group, irradiation control group 1,
      irradiation control group 2, irradiation control group 3, LBP + irradiation group
      1, LBP + irradiation group 2, and LBP + irradiation group 3. RESULTS: It is found
      that mating function and testis organ coefficient in LBP + irradiation groups
      were significantly better than that of the corresponding irradiation control
      groups. LBP significantly up-regulates the expression of Bcl-2 while down
      regulating the expression of Bax. And LBP also plays an important role in
      prevention mitochondrial membrane potential decrease. In addition, LBP can
      significantly reduce spermatogenic cells apoptosis. CONCLUSION: LBP has obvious
      protective effect on the male rats' reproductive function and spermatogenic
      dysfunction induced by irradiation.

PMID- 24746484
TI  - Assessment of Cuscuta chinensis seeds' effect on melanogenesis: comparison of
      water and ethanol fractions in vitro and in vivo.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Cuscuta chinensis seeds have traditionally been
      used to treat freckles and melasma in Asia, although recent reports have revealed
      that Semen cuscutae is a promoter of melanogenesis. The present study aims to
      investigate the mechanism of this opposite effect of Semen cuscutae on
      melanogenesis. MATERIALS AND METHODS: In accordance with traditional usage, the
      water fraction and the ethanol fraction from Semen cuscutae (WFSC/EFSC) were
      extracted to determine the herbal effects by examining the activity of mushroom
      tyrosinase, cellular melanin contents, tyrosinase activity assay, quantitative
      reverse transcription polymerase chain reaction (qRT-PCR), and Western blot
      analysis for tyrosinase in B16F10 mouse melanoma cells. The melanocyte phenotypes
      of zebrafish larvae were observed while the in vivo melanin contents and
      tyrosinase activity were determined. RESULTS: The activity of mushroom tyrosinase
      assay shown that WFSC was an uncompetitive inhibitor of mushroom tyrosinase,
      while EFSC indicated dose-dependent activation of the mushroom tyrosinase
      activity. The WFSC markedly inhibited 3-isobutyl-1-methylxanthine (IBMX)
      stimulated melanin synthesis and tyrosinase activity in vitro. Howeveran
      accelerant role in melanin synthesis and tyosinase activity. Neither fraction had
      any effect on the IBMX-induced expression of tyrosinase protein or mRNA. The WFSC
      strongly inhibited melanin synthesis and cellular tyrosinase activity in vivo.
      Furthermore, with the function of WFSC at a higher concentration, a punctate
      melanocyte pattern appeared that was similar to the pattern induced by arbutin or
      Mequinol (MQ). The EFSC had no effect on the melanocytes of zebrafish larvae. It
      was discovered that WFSC did not show a stable inhibitory effect until it was
      extracted 1 month later. CONCLUSIONS: These results suggest that the opposite
      effects of Cuscuta chinensis seeds were caused by the extraction methods and that
      time has an important role on the effect of WFSC. Both WFSC and EFSC
      significantly influence melanogenesis by regulating enzymatic activity of
      tyrosinase. In addition, the data indicate that wildtype (WT) zebrafish may be an
      ideal model for testing inhibitors of melanogenesis from clinically active herbs.

PMID- 24746485
TI  - Sex differences in response to reduced nicotine content cigarettes.
AB  - BACKGROUND: When switching from usual brand cigarettes, very low nicotine content
      (VLNC) cigarettes lead to a reduction in the number of cigarettes smoked,
      toxicant exposure, withdrawal symptoms and dependence. One area that has been
      relatively unexplored is what factors might moderate the effects of VLNC
      cigarettes. This exploratory analysis focuses on sex differences in responses to
      VLNC cigarettes and nicotine replacement therapy. METHODS: An exploratory
      secondary analysis of a randomized trial of 235 participants (58% female, mean
      age 47 years) comparing a) 0.05-0.09 mg nicotine yield cigarettes; b) 21 mg
      nicotine patch and 3) 0.05-0.09 nicotine yield cigarettes with 21 mg nicotine
      patch was conducted. We focused on sex differences in product use, and impact of
      products on withdrawal response from usual brand cigarettes and abstinence by
      randomized group. RESULTS: The combination of VLNC cigarettes and nicotine patch
      was more effective in reducing use of VLNC cigarettes and withdrawal symptoms
      among males than females, whereas females were equally responsive to VLNC
      cigarettes with and without the nicotine patch. Females were more likely to quit
      smoking than males when assigned to either of the conditions that incorporated
      the VLNC cigarettes; however, males were more likely to quit smoking in the
      nicotine patch alone condition than females. CONCLUSION: Sex of the smoker may be
      an important determinant for effects of VLNC cigarettes and nicotine patch.
      Future large randomized trials to confirm these results are needed.

PMID- 24746486
TI  - Cognitive and emotional profiles of aged Alzheimer's disease (3*TgAD) mice:
      effects of environmental enrichment and sexual dimorphism.
AB  - Alzheimer's disease is a neurodegenerative disorder associated with age which
      represents the most common cause of dementia. It is characterized by an
      accelerated memory loss compared to normal aging, and deterioration of other
      cognitive abilities that interfere with mood, reason, judgment and language. The
      main neuropathological hallmarks of the disorder are beta-amyloid (betaA) plaques
      and neurofibrillary Tau tangles. Triple transgenic 3*TgAD mouse model develops
      betaA and Tau pathologies in a progressive manner, with a specific temporal and
      anatomic profile mimicking the pattern that takes place in the human brain with
      AD, and showing cognitive alterations characteristic of the disease.
      Environmental enrichment treatment in mice induces behavioral and emotional
      reactivity changes, including cognitive improvements in some AD-related
      transgenic mice. The present work intended to characterize the behavioral profile
      of 3*TgAD mice at advanced stages of neuropathological development (12 and 15
      months of age) and to investigate whether environmental enrichment administered
      during adulthood was able to modify some of their behavioral and cognitive
      alterations. Results show that, at advanced stages of the disease 3*TgAD mice
      show deficits of spatial learning acquisition, as well as short-term and working
      memory deficits, while displaying increased levels of anxiety/fearfulness and
      normal sensorimotor functions. 3*TgAD mice also show sexual dimorphism, as
      reflected by increased cognitive deficits in females and increased levels of
      novelty-induced behavioral inhibition in males. Environmental enrichment exerts
      some slight positive effects, by mainly improving the initial acquisition of the
      spatial learning and working memory in 12-month-old 3*TgAD mice. Such effects
      vary depending on the gender. 

PMID- 24746487
TI  - Maternal separation exaggerates spontaneous recovery of extinguished contextual
      fear in adult female rats.
AB  - Early life stress increases the risk of posttraumatic stress disorders (PTSD).
      Patients with PTSD show impaired extinction of traumatic memory, and in women,
      this occurs more often when PTSD is preceded by child trauma. However, it is
      still unclear how early life stress accounts for extinction impairment. Here, we
      studied the effects of maternal separation (MS, postnatal day 2 to 14) on
      contextual fear extinction in adult female rats. Additionally, to examine changes
      in synaptic function affected by MS, we measured long-term potentiation (LTP) in
      prefrontal cortex and hippocampus in vitro, both of which have been implicated in
      fear extinction. We found that adult female rats had been subjected to MS
      exhibited significant spontaneous recovery of fear to the extinguished context.
      Furthermore, MS exposure resulted in LTP impairment in both infralimbic
      prefrontal cortex layer 2/3-layer 5 and hippocampal SC-CA1 pathways.
      Interestingly, no obvious effects of MS on contextual fear conditioning, fear
      recall as well as extinction training and recall were observed. Innate fear in
      the elevated plus maze or open field test remained nearly unaffected. These
      findings provided the first evidence that MS may exaggerate spontaneous recovery
      after contextual fear extinction, for which LTP impairment in the medial
      prefrontal cortex and hippocampus may be responsible, thereby possibly leading to
      impaired extinction associated with PTSD. 

PMID- 24746488
TI  - Selective orexin 2 receptor antagonism blocks cue-induced reinstatement, but not
      nicotine self-administration or nicotine-induced reinstatement.
AB  - The orexinergic system has been implicated in a number of behaviors, including
      reward and incentive motivation. Orexin 1 receptor antagonism has been reported
      to reduce drug self-administration, conditioned place preference, and
      reinstatement in rodents, but the role of the orexin 2 receptor is unclear. Here
      we evaluated the impact of the novel and selective orexin 2 receptor antagonist,
      2-SORA 18, on motivation for nicotine as measured by responding on a progressive
      ratio schedule, as well as cue-induced reinstatement of a response previously
      associated with nicotine reward, and nicotine-induced reinstatement. 2-SORA 18
      demonstrated selective effects on these behaviors. Specifically, doses up to 60
      mg/kg 2-SORA 18 were without significant effect on nicotine self-administration
      or nicotine-induced reinstatement, but doses as low as 15 mg/kg 2-SORA 18
      completely blocked cue-induced reinstatement. These findings indicate that orexin
      2 receptor antagonism might have utility for attenuating relapse, particularly
      for patients sensitive to environmental stimuli associated with drug taking.

PMID- 24746489
TI  - The utility of serial plasma sE-selectin measurements in the prediction of
      retinopathy of prematurity in premature infants.
AB  - BACKGROUND: sE-selectin has recently been suggested as a surrogate marker for
      prediction of ROP development. AIMS: The possible role of serial plasma sE
      selectin measurements in early prediction and diagnosis of ROP was evaluated.
      STUDY DESIGN: Prospective observational study SUBJECTS: Forty six preterm infants
      aged <34weeks of gestation and weighing <1500 g were enrolled. Of these, 26
      constituted the ROP group and 20 constituted the no-ROP group. sE-selectin levels
      were measured serially in blood samples on the 1st day and on 14th and 28th
      postnatal days. OUTCOME MEASURES: The primary outcome measure was to evaluate the
      role of sE-selectin concentrations in prediction of ROP. RESULTS: The mean
      gestational age and birth weight were significantly lower in the ROP group. The
      mean sE-selectin concentrations in ROP group were significantly greater than
      those in no-ROP group at each time point (1st, 14th and 28th days of postnatal
      life). A receiver operating characteristic (ROC) analysis showed that at a plasma
      concentration of >=86ng/mL on the 1st postnatal day, sE-selectin had a
      sensitivity of 100% and a specificity of 94.1% with a positive predictive value
      of 96.3% and a negative predictive value of 100%. Plasma sE-selectin
      concentrations were significantly greater in infants who developed ROP in three
      different time points. CONCLUSIONS: This study shows for the first time that
      measurement of plasma sE-selectin concentrations as early as the first day of
      life might help identify preterm infants at risk of ROP.

PMID- 24746490
TI  - Femoral component rotation in total knee arthroplasty: an MRI-based evaluation of
      our options.
AB  - Proper femoral component rotation is crucial in successful total knee
      arthroplasty. Rotation using anatomic landmarks has traditionally referenced the
      transepicondylar axis (TEA), Whiteside's Line (WSL), or posterior condylar axis
      (PCA). TEA is thought to best approximate the flexion-axis of the knee, however
      WSL or PCA are common surrogates in the operating room. This study evaluated 560
      knees using MRI-based planning software to assess the relationship of WSL and PCA
      to the TEA and determine if the relationships were influenced by pre-operative
      coronal deformity. Results showed the WSL-TEA relationship has more variability
      than PCA-TEA and that the PCA is more internally rotated in females and valgus
      knees. Axis options and historical assumptions about axis relationships may need
      to be reassessed as imaging technology advances. 

PMID- 24746491
TI  - A model of environmental correlates of adolescent obesity in the United States.
AB  - PURPOSE: The purpose of this study was to test a conceptual model of proximal
      (home) and distal (neighborhood) environmental correlates of adolescent obesity.
      METHODS: This was a descriptive, cross-sectional study, using the 2007 National
      Survey of Children's Health, of 39,542 children aged 11-17 years. Structural
      equation modeling was used to test the fit of the model, identify direct and
      indirect effects of the proximal and distal environmental correlates, and
      determine reliabilities for latent constructs (Access to Physical Activity,
      Neighborhood Conditions, Social Capital Home Sedentary Behavior, and Physical
      Activity). RESULTS: The model fitted the data well (Root Mean Square Standard
      Error of Approximation: .038 (90% confidence interval .038-.039), Comparative Fit
      Index: .950, and Tucker-Lewis Index: .934). Access to Physical Activity, Social
      Capital, Home Sedentary Behavior, and Physical Activity had direct effects on
      obesity (-.026, p = .001; .061, p < .001; .110, p < .001; and -.119, p < .001,
      respectively). Neighborhood Condition had indirect effects on obesity through
      Access to Physical Activity, Social Capital, and Home Sedentary Behavior (-.001,
      p = .009; .032, p < .001; and .044, p < .001, respectively). Access to Physical
      Activity had indirect effects on obesity through Physical Activity, Social
      Capital, and Home Sedentary Behavior (-.013, p < .001; -.005, p < .001; and 
      .005, p = .003, respectively). Home Sedentary Behavior had indirect effect on
      obesity through Physical Activity (.052, p <.001). CONCLUSIONS: Results of this
      model fit to the U. S. population-based data suggest that interventions should
      target not only sedentary behavior and physical activity but also parent
      perceptions of safety, access to physical activity, and the neighborhood
      condition.

PMID- 24746492
TI  - Trends and clustering of cardiovascular health metrics among U.S. adolescents
      1988-2010.
AB  - PURPOSE: American Heart Association recently published a set of seven
      cardiovascular (CV) health metrics for adults and children, emphasizing
      importance of preventing CV risk factors. Although CV disease risk factors have
      generally improved in adults, there is concern that this has not been true among
      adolescents. The present study examined trends and disparities of CV health
      metrics among U.S. adolescents. METHODS: We used data from a series of National
      Health and Nutrition Examination Survey (1988-1994, 1999-2004, and 2005-2010)
      including 11,233 adolescents aged 12-17 years. We estimated prevalence and mean
      score of CV health metrics and examined the disparities in mean score by sex,
      race/ethnicity, educational attainment, and poverty-income ratio. RESULTS: The
      prevalence of nonsmoking and healthy diet increased from 1988 through 2010, while
      the prevalence of normal body mass index and physical activity decreased,
      resulting in an unchanged distribution of overall CV health scores since 1988.
      The prevalence of adolescents meeting all seven CV health metrics was low, 3.5%
      (95% confidence interval [CI] 2.2-5.4), 4.0% (95% CI 3.3-4.8), and 4.0% (95% CI
      2.9-5.3) in National Health and Nutrition Examination Survey 1988-1994, 1999
      2004, and 2005-2010, respectively. The disparities in adjusted mean scores
      persisted between non-Hispanic whites and non-Hispanic blacks,
      families/households with >12 versus <12 years of education, and poverty-income
      ratio of >3 versus <3 (p < .05). CONCLUSIONS: The proportion of adolescents
      achieving all seven CV health metrics was low and remained unchanged during 1988
      2010. The disparities in mean CV health score persisted among adolescents.

PMID- 24746493
TI  - A time course study of acute traumatic coagulopathy prior to resuscitation: from
      hypercoagulation to hypocoagulation caused by hypoperfusion?
AB  - INTRODUCTION: Coagulopathy after sever injury predicts the requirements of blood
      products, organ failure and mortality in traumatic patients. The early onset and
      complexity of traumatic coagulopathy preclude the understanding the underlying
      mechanism. The aim of the study is to characterize the early coagulation
      alteration in a swine model with multi-trauma and shock. METHODS: Twelve pigs
      were subjected to multi-trauma (femur fracture, laparotomy, 10 cm intestine
      resection and grade III injury of liver) and hemorrhaged to a mean arterial
      pressure (MAP) of 40 mmHg. Physiologic parameters and coagulation variables
      (prothrombin time (PT), international normalized ratio (INR), fibrinogen,
      antithrombin-III (AT-III) activity, D-dimer and thromboelastography (TEG)) were
      measured after instrumentation (baseline), 5 min after multi-trauma (after
      trauma), 10 min (early shock) and 40 min (late shock) after hemorrhage. A group
      of 6 instrumented pigs were used as control. RESULTS: Multi-trauma and hemorrhage
      caused significant increase of base excess (BE) and lactate (p<0.05). PT
      shortened after multi-trauma but increased significantly at late shock (p<0.05).
      Fibrinogen reduced greatly after trauma and at early shock (p<0.05), while
      remained stable afterwards. AT-III activity decreased throughout the experiment.
      Reaction time (R) shortened after trauma and at early shock (both p<0.05).
      Maximal amplitude (MA) decreased significantly during the shock period.
      CONCLUSION: After traumatic hemorrhagic shock, hypercoagulation turned into
      hypocoagulation in a short period, which was probably caused by hypoperfusion.

PMID- 24746494
TI  - Functional interest of an articulating spacer in two-stage infected total knee
      arthroplasty revision.
AB  - INTRODUCTION: Deep periprosthetic infection is one of the most serious
      complications after total knee replacement. The two-stage procedure with
      implantation of a temporary cement spacer and later re-implantation of a revision
      total knee prosthesis is an accepted procedural standard. The use of articulating
      spacers has been proposed to enhance ease of revision and functional results.
      PATIENTS AND METHODS: Twenty-three patients treated with an articulating spacer
      were retrospectively studied. All patients had undergone a two-stage surgery. The
      infected prosthesis was explanted and the femoral component was sterilized and re
      implanted. On the tibial side a block of gentamicin-loaded bone cement was
      produced intraoperatively using specially manufactured templates. Eighteen total
      knee arthroplasty revisions and 5 arthrodesis were finally performed. RESULTS: A
      total of three (13%) re-infections occurred 5-20 months after revision total knee
      arthroplasty in a mean follow-up period of 47 months. Prior to re-implantation,
      flexion with the articulating spacer ranged between 15 and 100 degrees  (mean
      68+/-28 degrees ). The average postoperative flexion after re-implantation of
      total knee replacement was 105+/-11 degrees . CONCLUSION: The articulating spacer
      used in this study appears to be as effective as the standard procedures in terms
      of re-infection risk rate and postoperative range of motion recovery. LEVEL OF
      EVIDENCE: Level IV.

PMID- 24746495
TI  - Brain stem slice conditioned medium contains endogenous BDNF and GDNF that affect
      neural crest boundary cap cells in co-culture.
AB  - Conditioned medium (CM), made by collecting medium after a few days in cell
      culture and then re-using it to further stimulate other cells, is a known
      experimental concept since the 1950s. Our group has explored this technique to
      stimulate the performance of cells in culture in general, and to evaluate stem-
      and progenitor cell aptitude for auditory nerve repair enhancement in particular.
      As compared to other mediums, all primary endpoints in our published experimental
      settings have weighed in favor of conditioned culture medium, where we have shown
      that conditioned culture medium has a stimulatory effect on cell survival. In
      order to explore the reasons for this improved survival we set out to analyze the
      conditioned culture medium. We utilized ELISA kits to investigate whether brain
      stem (BS) slice CM contains any significant amounts of brain-derived neurotrophic
      factor (BDNF) and glial cell derived neurotrophic factor (GDNF). We further
      looked for a donor cell with progenitor characteristics that would be receptive
      to BDNF and GDNF. We chose the well-documented boundary cap (BC) progenitor cells
      to be tested in our in vitro co-culture setting together with cochlear nucleus
      (CN) of the BS. The results show that BS CM contains BDNF and GDNF and that
      survival of BC cells, as well as BC cell differentiation into neurons, were
      enhanced when BS CM were used. Altogether, we conclude that BC cells transplanted
      into a BDNF and GDNF rich environment could be suitable for treatment of a
      traumatized or degenerated auditory nerve. 

PMID- 24746496
TI  - Assembly of the FKBP51-PHLPP2-AKT signaling complex in cerebral
      ischemia/reperfusion injury in rats.
AB  - The imbalance of cell pro-death and pro-survival signaling pathways determines
      the neuronal fate during cerebral ischemia/reperfusion (I/R) injury. However, the
      biological mechanisms regulating the balance between activation of the pro-death
      or the pro-survival signaling pathways remain unclear. In this study, a rat model
      of I/R injury was established using four-vessel occlusion followed by different
      times of reperfusion. I/R injury did not affect the level of FK506 binding
      protein 51 (FKBP51), PH domain and leucine rich repeat protein phosphatases
      (PHLPP)-2, and AKT, but induced assembly of the FKBP51-PHLPP2-AKT signaling
      complex, as indicated by the enhancement of interactions among these compounds
      following reperfusion. Using an antisense oligonucleotide, PHLPP2 expression was
      effectively inhibited. Critically, the inhibition of PHLPP2 prohibited the
      interactions of FKBP51, PHLPP2 and AKT, reversed the decrease of p-AKT expression
      and increased the expression of p-JNKs and p-c-Jun elicited by I/R injury. In
      addition, PHLPP2 inhibition reversed I/R-injury-induced Caspase-3 cleavage and
      loss of pyramid neurons in the CA1 region of hippocampus. The results of the
      current study indicate that the assembly of the FKBP51-PHLPP2-AKT signaling
      complex plays a critical role in mediating cell death in I/R injury. The
      inhibition of PHLPP2 via antisense oligonucleotide treatment may be an effective
      method to prohibit the assembly of the FKBP51-PHLPP-AKT signaling complex, thus
      balancing the cell pro-survival and pro-death signaling pathways ultimately
      mitigating cell death in I/R injury.

PMID- 24746497
TI  - Semantic relation vs. surprise: the differential effects of related and unrelated
      co-verbal gestures on neural encoding and subsequent recognition.
AB  - Speech-associated gesturing leads to memory advantages for spoken sentences.
      However, unexpected or surprising events are also likely to be remembered. With
      this study we test the hypothesis that different neural mechanisms (semantic
      elaboration and surprise) lead to memory advantages for iconic and unrelated
      gestures. During fMRI-data acquisition participants were presented with video
      clips of an actor verbalising concrete sentences accompanied by iconic gestures
      (IG; e.g., circular gesture; sentence: "The man is sitting at the round table"),
      unrelated free gestures (FG; e.g., unrelated up down movements; same sentence)
      and no gestures (NG; same sentence). After scanning, recognition performance for
      the three conditions was tested. Videos were evaluated regarding semantic
      relation and surprise by a different group of participants. The semantic
      relationship between speech and gesture was rated higher for IG (IG>FG), whereas
      surprise was rated higher for FG (FG>IG). Activation of the hippocampus
      correlated with subsequent memory performance of both gesture conditions
      (IG+FG>NG). For the IG condition we found activation in the left temporal pole
      and middle cingulate cortex (MCC; IG>FG). In contrast, for the FG condition
      posterior thalamic structures (FG>IG) as well as anterior and posterior cingulate
      cortices were activated (FG>NG). Our behavioral and fMRI-data suggest different
      mechanisms for processing related and unrelated co-verbal gestures, both of them
      leading to enhanced memory performance. Whereas activation in MCC and left
      temporal pole for iconic co-verbal gestures may reflect semantic memory
      processes, memory enhancement for unrelated gestures relies on the surprise
      response, mediated by anterior/posterior cingulate cortex and thalamico
      hippocampal structures. 

PMID- 24746498
TI  - Valproic acid enhances the effect of bone marrow-derived mononuclear cells in a
      rat ischemic stroke model.
AB  - Bone marrow derived mononuclear cell (MNC) transplantation is a potential therapy
      for ischemic stroke. Here, we hypothesized that valproic acid (VPA) would
      modulate transplantation effects of MNCs in a rat ischemic stroke model. Male
      Sprague-Dawley rats were subjected to transient 90min middle cerebral artery
      occlusion. Infarct volume, neurological outcome, and immunohistological
      assessments were performed 7 days after ischemia. MNCs injected 6 or 24h but not
      48 or 72h after ischemia significantly reduced infarct volume and improved
      neurological deficits. We then tested whether the therapeutic window of MNC
      transplantation could be expanded through combination therapy with VPA. MNC
      transplantation at 48h combined with VPA injection three times at 47, 53, and 72h
      after ischemia significantly ameliorated infarct volume and neurological deficits
      compared to a vehicle group. Combination therapy reduced the number of
      myeloperoxidase-positive cells, ionized calcium binding adapter molecule 1
      positive cells, tumor necrosis factor-alpha-positive cells, and von Willebrand
      factor-positive cells in the ischemic boundary zone. The number of engrafted MNCs
      that were fluorescently labeled with PKH 26, on day 7, was significantly higher
      after combination therapy than after that MNC transplantation alone. Our results
      demonstrated that combination therapy with VPA enhanced the anti-inflammatory and
      vasculo-protective effects against endothelial damage following ischemia, and
      increased the survival of transplanted cells, leading to expansion of the
      therapeutic time window for MNC transplantation. Together, these findings suggest
      that VPA may be an appropriate partner for cell-based treatment of ischemic
      stroke. 

PMID- 24746499
TI  - Costs and mortality associated with atrial fibrillation complicated by myocardial
      infarction in the United States.

PMID- 24746500
TI  - Clinical feasibility of myocardial computed tomographic perfusion imaging in
      patients with recent acute-onset chest pain.

PMID- 24746501
TI  - Al-Baghdadi's description of venous blood circulation.

PMID- 24746502
TI  - Change in health-related quality of life in patients with coronary artery disease
      predicts 4-year mortality.
AB  - AIMS: Self-reported health-related quality of life (HRQL) and changes in HRQL
      have been shown to predict mortality and/or adverse events in patients with
      coronary artery disease. MacNew Heart Disease HRQL questionnaire scores were
      examined as predictors of 4-year all-cause mortality. METHODS: Following referral
      for angioplasty in 385 patients with coronary artery disease, data were analyzed
      for differences in all-cause mortality by MacNew Global and subscale baseline and
      1- and 3-month change scores (deteriorated >=0.50; unchanged (-0.49 to +0.49);
      and improved >=0.50 points). RESULTS: Mean baseline, 1-month, and 3-month MacNew
      Global and subscale scores were similar in survivors and non-survivors. Mean 1-
      and 3-month Global and emotional subscale and mean 1-month social subscale change
      scores decreased more in non-survivors than survivors. Compared with patients
      whose Global MacNew HRQL scores improved at one month, 4-year all-cause mortality
      hazard ratio (HR) was higher in patients whose HRQL deteriorated (HR, 1.70, 95%
      CI, 1.09, 2.65; p=0.021). Compared with patients whose Global MacNew HRQL
      improved at three months, 4-year all-cause mortality was higher in both patients
      whose HRQL had deteriorated (HR, 2.07, 95% CI, 1.29, 3.32; p=0.003) and patients
      with unchanged HRQL (HR, 2.62, 95% CI, 1.11, 6.17; p=0.028). CONCLUSIONS: A
      deterioration of >=0.50 points in MacNew HRQL Global scores at both one and three
      months is predictive of 4-year all-cause mortality. Serial HRQL information may
      be useful to identify patients at higher risk for adverse cardiac events and
      mortality and may have implications for determining follow-up frequency and
      treatment in individual patients.

PMID- 24746503
TI  - Myasthenia gravis and heart failure: is ivabradine a useful drug?

PMID- 24746504
TI  - Angioplasty and stenting in middle cerebral artery: results from multicenter
      China interventional stroke registry.

PMID- 24746505
TI  - Bicuspid aortic valve disease and lipoprotein(a)--a concept worth exploring?

PMID- 24746506
TI  - Sunitinib-associated thrombotic microangiopathy: a significant risk.

PMID- 24746507
TI  - Longitudinal ultrasonic vibration assisted guillotining of stacked paper.
AB  - Ultrasonic vibration assisted cutting is a complex process with high dynamics.
      The interaction between cutting tool and workpiece is of key interest to
      understand the entire process. Experimental investigations are limited by the
      dynamics of the measurement system, and thus appropriately modeling of the
      ultrasonic vibration assisted cutting process is essential. In this
      investigation, a dynamic model regarding the ultrasonic vibration assisted
      guillotining of stacked paper sheets is developed. A Kelvin-Voigt material model,
      representing the individual sheets, is chosen, with its stiffness and damping
      parameters being empirically determined. A novel measurement strategy for
      studying the contact time and interaction between cutting tool and workpiece is
      introduced. It allows the verification of the highly dynamic behavior of the
      developed model. With the dynamic model, the experimentally observed cutting
      forces can be calculated. It is found that the dynamic forces cause a quicker
      failure of the material, which leads to a lower compression of the stack prior to
      reaching the critical cutting force. 

PMID- 24746508
TI  - Effect of ultrasonic treatment on heavy metal decontamination in milk.
AB  - Ultrasound has been found useful in increasing the efficiency and consumer safety
      in food processing. Removal of heavy metal (lead, mercury, and arsenic)
      contamination in milk is extremely important in regions of poor ecological
      environment - urban areas with heavy motor traffic or well established
      metallurgical/cement industry. In this communication, we report on the
      preliminary studies on the application of low frequency (20kHz) ultrasound for
      heavy metal decontamination of milk without affecting its physical, chemical, and
      microbiological properties. 

PMID- 24746509
TI  - Ultrasound assisted immersion freezing of broccoli (Brassica oleracea L. var.
      botrytis L.).
AB  - OBJECTIVE: The aim of this study was to research the ultrasound-assisted freezing
      (UAF) of broccoli. METHODS: CaCl2 solution was used as freezing medium. The
      comparative advantage of using UAF over normal freezing on the freezing time,
      cell-wall bound calcium to total calcium ratio, textural properties, color, drip
      loss and L-ascorbic acid contents was evaluated. RESULTS: The application of UAF
      at selected acoustic intensity with a range of 0.250-0.412 W/cm(2) decreased the
      freezing time and the loss of cell-wall bound calcium content. Compared to normal
      freezing, the values of textural properties, color, L-ascorbic acid content were
      better preserved and the drip loss was significantly minimized by the application
      of UAF. However, when outside that range of acoustic intensity, the quality of
      the ultrasound-assisted frozen broccoli was inferior compared to that of the
      normally frozen samples. CONCLUSIONS: Selected the appropriate acoustic intensity
      was very important for the application of UAF.

PMID- 24746510
TI  - Self-assembled 3D sphere-like SrMoO4 and SrMoO4:Ln3+ (Ln=Eu, Sm, Tb, Dy)
      microarchitectures: facile sonochemical synthesis and optical properties.
AB  - Three-dimensional (3D) well-defined SrMoO4 and SrMoO4:Ln(3+) (Ln=Eu, Sm, Tb, Dy)
      hierarchical structures of obvious sphere-like shape have been successfully
      synthesized using a large-scale and facile sonochemical route without using any
      catalysts or templates. X-ray diffraction (XRD), field-emission scanning electron
      microscopy (FE-SEM), energy dispersive X-ray spectroscopy (EDS), and
      photoluminescence (PL) spectra were used to characterize the samples. The
      intrinsic structural feature of SrMoO4 and external factor, namely the ultrasonic
      time and the pH value, are responsible for the ultimate shape evolutions of the
      product. The possible formation mechanism for the product is presented.
      Additionally, the PL properties of SrMoO4 and SrMoO4:Ln(3+) (Ln=Eu, Sm, Tb, Dy)
      hierarchical structures were investigated in detail. The Ln(3+) ions doped SrMoO4
      samples exhibit respective bright red-orange, yellow, green and white light of
      Eu(3+), Sm(3+), Tb(3+) and Dy(3+) under ultraviolet excitation, and have
      potential application in the field of color display. Simultaneously, this novel
      and efficient pathway could open new opportunities for further investigating
      about the properties of molybdate materials. 

PMID- 24746511
TI  - Doxycyclin ameliorates a starvation-induced germline tumor in C. elegans daf
      18/PTEN mutant background.
AB  - Managing available resources is a key necessity of each organism to cope with the
      environment. The nematode C. elegans responds to nutritional deprivation or harsh
      environmental conditions with a multitude of developmental adaptations, among
      them a starvation-induced quiescence at early larval development (L1). daf-18,
      the C. elegans homolog of the human tumor suppressor gene PTEN, is essential for
      the maintenance of survival and germline stem cell arrest during the L1 diapause.
      We show here that daf-18 mutants, independently to their failure to maintain G2
      arrest of the primordial germ cells, develop a gonad phenotype after refeeding.
      This highly penetrant gonadal phenotype is further enhanced by a mutation in shc
      1, encoding a protein homologous to the human adaptor ShcA. Features of this
      phenotype are a tumor-like phenotype encompassing hyper-proliferation of germ
      cell nuclei and disruption/invasion of the basement membrane surrounding the
      gonad. The penetrance of this phenotype is reduced by decreasing starvation
      temperature. In addition, it is also ameliorated in a dose-dependent way by
      exposure to the antibiotic doxycyclin either during starvation or during
      subsequent refeeding. Since, in eukaryotic cells, doxycyclin specifically blocks
      mitochondrial translation, our results suggest that daf-18 and shc-1;daf-18
      mutants fail to adapt mitochondrial activity to reduced nutritional availability
      during early larval developing. 

PMID- 24746512
TI  - The association between physical activity and reduced body fat lessens with age -
      results from a cross-sectional study in community-dwelling older adults.
AB  - INTRODUCTION: The aim of this study was to describe the relationship between
      accelerometer-determined physical activity (PA) and adiposity in community
      dwelling older adults. In addition, we were interested in comparing the extent of
      correlation between questionnaire and accelerometer determined PA. METHODS: 636
      community-dwelling older adults (66+/-7years) were studied. Adiposity was
      measured using dual-energy X-ray absorptiometry and BMI was calculated. We
      measured minutes/day spent in sedentary, light, moderate and vigorous intensity
      activity using both questionnaires and Actigraph GT1M accelerometers. RESULTS:
      Participants spent a median of 583(IQR 522-646), 225(176-271), 27(12-45) and 0(0
      0) minutes in sedentary, light, moderate and vigorous activities respectively.
      There was a non linear dose-response inverse relationship between activity
      intensity and adiposity. After adjusting for age, sex and other levels of PA, for
      every 10minute increase in activity, total body fat decreased by 169g(95% CI 61
      277), 905g(632-1178), and 2208g(759-3657) for light, moderate and vigorous
      activities respectively. There was an interaction between age and activity; as
      age increased, the magnitude of the effects of light and moderate activities on
      adiposity decreased. Sedentary minutes were not associated with adiposity after
      adjusting for time spent at other PA intensities. Questionnaire measures of PA
      were weakly correlated with body fat measures when compared to accelerometer
      determined PA. CONCLUSION: Both the amount and intensity of PA, but not sedentary
      time, have an independent dose-response association with adiposity. The
      association is much stronger using objective assessment compared to
      questionnaire. The magnitude of these associations decrease with age suggesting
      that physical activity programmes may need to be modified with increasing age.

PMID- 24746513
TI  - Aged Chinese rhesus macaques suffer severe phenotypic T- and B-cell aging
      accompanied with sex differences.
AB  - The elderly usually suffer from increased morbidity and mortality due to
      infectious diseases, and this process may be attributed to diminishing immune
      protection with age. This phenomenon is commonly referred to as immunosenescence.
      However, this theory is still not well defined. Non-human primates serve as a
      favorable model to facilitate the study in aging of the immune system. Here, we
      investigated the phenotypic features of T- and B-cell aging in peripheral blood
      from Chinese rhesus macaques, which included (1) a decrease of CD4/CD8 ratio; (2)
      a loss of naive T cells accompanied with elevated proliferation and expansion of
      effector memory subset; (3) a reduction in B cell numbers and a shift from naive
      B cells towards memory phenotype; and (4) increased levels of PD-1 expression in
      T cells and CD95 expression in B cells. Moreover, an accelerated decline in
      CD4(+) T cells and naive T cells was found in male macaques, giving them a more
      severe immune risk profile. These data indicated that Chinese rhesus macaques
      share a significant homology with humans in phenotypic aging of adaptive
      immunity, and may be an appropriate animal model for human aging research. 

PMID- 24746514
TI  - Gene-gene interaction between CETP and APOE polymorphisms confers higher risk for
      hypertriglyceridemia in oldest-old Chinese women.
AB  - The knowledge of dyslipidemia and its genetic contributors in oldest-old subjects
      is limited; in addition, the majority of oldest-old subjects are females.
      Evidence has accumulated that multiple genetic factors play important roles in
      determining susceptibility to dyslipidemia and extended life span. Cholesterol
      ester transfer protein (CETP) and apolipoprotein E (APOE) are two plausible
      candidate genes for human longevity owing to their functionally related
      modulation of circulating lipid homeostasis; however, few studies have considered
      their interplay. In this study, we analyzed the distribution of CETP*V (rs5882)
      and APOE*4 (rs429358 and rs7412) in 372 oldest-old Chinese women (aged 80-109)
      and 340 controls (aged 20-58). In addition to replicating the association of
      longevity, our main goal was to evaluate the contribution of CETP*V, APOE*4 and
      CETP*APOE interaction to the risk of dyslipidemia. Only APOE*4 conferred a risk
      against longevity and was associated with high-cholesterol (hTC) and mixed
      dyslipidemia for oldest-old females. Moreover, CETP*V was found to be associated
      with hypertriglyceridemia (hTG) independently from APOE*4, age, BMI, alcohol
      drinking, TC, TG, HDL-c, and LDL-c. The stratification test, multivariable
      adjusted logistic regression, and nonparametric MDR analysis all suggested a
      significant CETP*APOE interaction associated with hTG. The unadjusted odds for
      hTG were more than 4-fold in subjects with CETP*V and APOE*4 than those without
      either (OR=4.36, P<0.001). These results provide evidence of strong independent
      associations between hTG and CETP*V in oldest-old Chinese females, and APOE*4, as
      an independently non-significant variant, might interact with CETP*V resulting in
      an increased risk for hTG. 

PMID- 24746515
TI  - Bilateral femoral artery compression as a technique to increase vital organ
      perfusion during intraoperative hypotension.
AB  - Intraoperative hypotension is associated with adverse outcomes. The preferred
      treatment for intraoperative hypotension is to address its cause. In the interim
      the blood pressure can be supported by the anesthesia team with volume
      resuscitation and vasopressors. Additionally, preferential perfusion of vital
      organs, such as the myocardium and cerebrum, at the expense of non-vital vascular
      beds, such as the extremities, is desirable. In the state of shock, the flight or
      fight response will ensure perfusion of the extremities in order to prepare the
      organism for a physical confrontation. However, in the context of intraoperative
      hypotension this response is counter-productive. Therefore we propose bilateral
      femoral artery compression as a new technique to increase vital organ perfusion
      during intraoperative hypotension. This results in shunting of blood flow from
      the legs and towards the vital organs. Bilateral femoral artery compression can
      be employed by the surgical team to immediately improve blood pressure until
      other counter-measures against intraoperative hypotension take effect.

PMID- 24746516
TI  - beta-catenin is a valuable marker for differential diagnosis of osteoblastoma and
      osteosarcoma.
AB  - Osteoblastoma (OB) and osteosarcoma (OS) are 2 bone tumors that predominantly
      affect young adults. The clinical management of OS differs significantly from
      that of OB, and thus, accurate diagnosis of OB and OS is critical in determining
      appropriate treatment modality. However, in certain cases, OS significantly
      overlaps with OB in clinical and radiographic characteristics, and therefore, the
      differential diagnosis of OB and OS can be difficult, especially when biopsy
      material is insufficient. To date, there have been few reports on markers for
      differential diagnosis of OB and OS. We have previously shown that the Wnt/beta
      catenin pathway is inactivated in OS. In this study, we aimed to investigate
      whether the cellular distribution pattern of beta-catenin is a potential marker
      for the differential diagnosis of OB and OS. Immunohistochemical staining was
      studied in 17 OB samples (21 biopsies; 17 primary and 4 recurrent) and 37 OS
      samples with complete follow-up information. Moderate-to-strong nuclear beta
      catenin staining was found in all OB specimens (17/17). In contrast, positive
      staining of beta-catenin was found in the cytoplasm and/or membrane but not the
      nucleus in all 32 cases of nonchondroblastic OS (32/32) and the classic OS
      component in chondroblastic OS (5/5). The only positive nuclear beta-catenin
      staining detected in OS biopsies was in chondroblastic OS cells (5/5). In
      summary, our results indicate that, in addition to conventional histopathologic
      evaluation, cellular distribution of beta-catenin may be used as a valuable
      marker in the differential diagnosis of OB and OS. Nuclear beta-catenin staining
      strongly suggests OB, whereas cytoplasmic/membranous staining of beta-catenin
      suggests OS. 

PMID- 24746517
TI  - The value of interventional radiology in re-establishment of lost access to
      catheterizable channels to the bladder and bowel.
AB  - OBJECTIVE: The efficacy of interventional radiology (IR) procedures in regaining
      lost access to continent catheterizable channels in pediatric urology patients is
      uninvestigated. This paper assesses this efficacy, as well as prevention of
      surgical revision of these channels as a result of IR intervention. METHODS: A
      retrospective chart analysis was performed over 8 years for children presenting
      with lost access to the bladder or bowel that could not be regained by a
      pediatric urologist. Rates of successful re-establishment of access in IR and the
      need for future surgical revision were calculated. RESULTS: Twenty pediatric
      patients underwent 32 attempts to re-establish lost access in IR. IR was
      successful in 78.1% (25/32) of episodes for 15/20 patients. No intervention
      required general anesthesia. Thirty percent (6/20) were able to avoid surgical
      revision. Another 45% (9/20) had access re-established in IR but later had
      surgery related to their channel (endoscopic, percutaneous, or open). Only three
      patients required open revision. The five patients in whom IR access failed, did
      require surgery. CONCLUSION: Image-guided re-establishment of access to continent
      catheterizable channels in children is efficacious. It can diffuse an emergency
      situation and delay or obviate the need for surgical correction. Additionally, a
      general anesthetic is not necessary.

PMID- 24746518
TI  - Colicin import into E. coli cells: a model system for insights into the import
      mechanisms of bacteriocins.
AB  - Bacteriocins are a diverse group of ribosomally synthesized protein antibiotics
      produced by most bacteria. They range from small lanthipeptides produced by
      lactic acid bacteria to much larger multi domain proteins of Gram negative
      bacteria such as the colicins from Escherichia coli. For activity bacteriocins
      must be released from the producing cell and then bind to the surface of a
      sensitive cell to instigate the import process leading to cell death. For over
      50years, colicins have provided a working platform for elucidating the
      structure/function studies of bacteriocin import and modes of action. An
      understanding of the processes that contribute to the delivery of a colicin
      molecule across two lipid membranes of the cell envelope has advanced our
      knowledge of protein-protein interactions (PPI), protein-lipid interactions and
      the role of order-disorder transitions of protein domains pertinent to protein
      transport. In this review, we provide an overview of the arrangement of genes
      that controls the synthesis and release of the mature protein. We examine the
      uptake processes of colicins from initial binding and sequestration of binding
      partners to crossing of the outer membrane, and then discuss the translocation of
      colicins through the cell periplasm and across the inner membrane to their
      cytotoxic site of action. This article is part of a Special Issue entitled:
      Protein trafficking and secretion in bacteria. Guest Editors: Anastassios
      Economou and Ross Dalbey. 

PMID- 24746520
TI  - Diverse roles of ANGPTL2 in physiology and pathophysiology.
AB  - Stresses based on aging and lifestyle can cause tissue damage. Repair of damage
      by tissue remodeling is often meditated by communications between parenchymal and
      stromal cells via cell-cell contact or humoral factors. However, loss of tissue
      homeostasis leads to chronic inflammation and pathological tissue remodeling.
      Angiopoietin-like protein 2 (ANGPTL2) maintains tissue homeostasis by promoting
      adaptive inflammation and subsequent tissue reconstruction, whereas excess
      ANGPTL2 activation induced by prolonged stress promotes breakdown of tissue
      homeostasis due to chronic inflammation and irreversible tissue remodeling,
      promoting development of various metabolic diseases. Thus, it is important to
      define how ANGPTL2 signaling is regulated in order to understand mechanisms
      underlying disease development. Here, we focus on ANGPTL2 function in physiology
      and pathophysiology. 

PMID- 24746519
TI  - Self-eating in the plaque: what macrophage autophagy reveals about
      atherosclerosis.
AB  - Autophagy (or 'self-eating') is the process by which cellular contents are
      recycled to support downstream metabolism. An explosion in research in the past
      decade has implicated its role in both health and disease and established the
      importance of the autophagic response during periods of stress and nutrient
      deprivation. Atherosclerosis is a state where chronic exposure to cellular
      stressors promotes disease progression, and alterations in autophagy are
      predicted to be consequential. Recent reports linking macrophage autophagy to
      lipid metabolism, blunted inflammatory signaling, and an overall suppression of
      proatherogenic processes support this notion. We review these data and provide a
      framework for understanding the role of macrophage autophagy in the pathogenesis
      of atherosclerosis, one of the most formidable diseases of our time. 

PMID- 24746521
TI  - Hydrogen sulfide in hemostasis: friend or foe?
AB  - Hydrogen sulfide (H2S) is a well known toxic gas that is synthesized from the
      amino acids: cysteine (Cys) and homocysteine (Hcy) by three enzymes:
      cystathionine-beta-synthase (CBS), cystathionine-gamma-lyase (CSE) and
      mercaptopyruvate sulfurtransferase (3-MST). Hydrogen sulfide, like carbon
      monoxide (CO) or nitric oxide (NO) is a signaling molecule in different
      biological systems, including the cardiovascular system. Moreover, hydrogen
      sulfide plays a role in the pathogenesis of various cardiovascular diseases. It
      modulates different elements of hemostasis (activation of blood platelet, and
      coagulation process) as well as proliferation and apoptosis of vascular smooth
      muscle cells. However, the biological role and the therapeutic potential of H2S
      is not clear. This review summarizes the different functions of hydrogen sulfide
      in hemostasis. 

PMID- 24746522
TI  - Primer of statistics in dental research: Part II.
AB  - The Part I of Primer of Statistics in Dental Research covered five topics that
      are often mentioned in statistical check list of many peer-review journals
      including (1) statistical graph, (2) how to deal with outliers, (3) p-value and
      confidence interval, (4) testing equivalence, and (5) multiplicity Adjustment.
      The Part II of the series covers another set of important topics in dental
      statistics including (1) selecting the proper statistical tests, (2) repeated
      measures analysis, (3) epidemiological consideration for causal association, and
      (4) analysis of agreement. First, a guide in selecting the proper statistical
      tests based on the research question will be laid out in text and with a table so
      that researchers choose the univariable statistical test by answering five simple
      questions. Second, the importance of utilizing repeated measures analysis will be
      illustrated. This is a key component of data analysis as in many dental studies,
      observations are considered repeated in a single patient (several teeth are
      measured in a single patient). Third, concepts of confounding and the use of
      regression analysis are explained by going over a famous observational cohort
      study. Lastly, the use of proper agreement analysis vs. correlation for study of
      agreement will be discussed to avoid a common pitfall in dental research.

PMID- 24746523
TI  - Prosthodontic interventions for special-needs patients.

PMID- 24746524
TI  - Clinical application of removable partial dentures using thermoplastic resin.
      Part II: Material properties and clinical features of non-metal clasp dentures.
AB  - This position paper reviews physical and mechanical properties of thermoplastic
      resin used for non-metal clasp dentures, and describes feature of each
      thermoplastic resin in clinical application of non-metal clasp dentures and
      complications based on clinical experience of expert panels. Since products of
      thermoplastic resin have great variability in physical and mechanical properties,
      clinicians should utilize them with careful consideration of the specific
      properties of each product. In general, thermoplastic resin has lower color
      stability and higher risk for fracture than polymethyl methacrylate.
      Additionally, the surface of thermoplastic resin becomes roughened more easily
      than polymethyl methacrylate. Studies related to material properties of
      thermoplastic resin, treatment efficacy and follow-up are insufficient to provide
      definitive conclusions at this time. Therefore, this position paper should be
      revised based on future studies and a clinical guideline should be provided. 

PMID- 24746525
TI  - Removal of polar UV stabilizers in biological wastewater treatments and
      ecotoxicological implications.
AB  - The present study describes the development, validation and application of a
      fully automated analytical method based on on-line solid-phase extraction-liquid
      chromatography-tandem mass spectrometry (on line SPE-HPLC-MS/MS) to assess the
      removal efficiency in water works and the ecotoxicological implications derived
      of the two most used benzotriazole-class UV stabilizers (BZTs), namely 1H
      benzotriazole (BZT) and 5-methyl-1H-benzotriazole (MeBZT). Influent and effluent
      wastewater samples from 20 wastewater treatment plants (WWTPs) were analyzed.
      Removal rates (RE%) and half-lives (t1/2) for each BZTs were calculated and
      correlated to the hydraulic retention time (HRT) of each plant. Both BZTs were
      detected in all influent and effluent samples (concentrations in the range 26.7
      ng L(-1)-42.9 MUg L(-1)), with the highest concentrations corresponding to MeBZT.
      Results indicated that both compounds were recalcitrant (RE% in the range 11.8
      94.7%) and that no clear influence of HRT on removals could be drawn. Finally,
      the potential environmental risk posed by the levels of BZTs detected was
      evaluated calculating the hazard quotients (HQs) MeBZT was the only BZTs posing a
      risk to Vibrio fischeri, Daphnia galeata and Pimephales promelas.

PMID- 24746526
TI  - Comment on "The environmental photolysis of perfluorooctanesulfonate,
      perfluorooctanoate, and related fluorochemicals".

PMID- 24746527
TI  - Predictors of quality of life and functional impairment in obsessive-compulsive
      disorder.
AB  - Obsessive-compulsive disorder (OCD) is the 10th leading cause of disability among
      health conditions; yet, relatively little research has focused on quality of life
      (QOL) and functional impairment in OCD. The present study extended existing work
      by examining correlates and predictors of QOL and functional impairment in 96
      treatment-seeking OCD patients (in intensive outpatient and residential
      settings). In a model including OCD symptoms and related phenomena, and symptoms
      of depression and anxiety, two main findings emerged: (a) depressive symptoms
      predicted both QOL and functional impairment, and (b) contamination symptoms
      predicted functional impairment. These findings are discussed in terms of the
      implications for studying QOL and functional impairment in OCD. Future research
      should investigate the factors that predict changes in QOL and functional
      impairment following treatment. 

PMID- 24746528
TI  - Prevalence and clinical correlates of alcohol use disorders among bipolar
      disorder patients: results from the Brazilian Bipolar Research Network.
AB  - OBJECTIVES: To investigate prevalence rates and clinical correlates of alcohol
      use disorders (AUD) among bipolar disorder (BD) patients in a large sample from
      the Brazilian Bipolar Research Network. METHODS: Four hundred and eighty-three
      DSM-IV BD patients, divided according to the presence or absence of a lifetime
      AUD diagnosis (BD-AUD vs. BD-nonAUD), were included. Demographic and clinical
      characteristics of these two groups were compared. Logistic regression was
      performed to identify which characteristics were most strongly associated with a
      lifetime AUD diagnosis. RESULTS: Nearly 23% presented a lifetime AUD diagnosis.
      BD-AUD patients were more likely to be male, to present rapid cycling, post
      traumatic stress disorder (PTSD), anorexia, other substance use disorders (SUD),
      family history of SUD, any substance misuse during the first mood episode,
      history of psychosis, suicide attempts, and younger age at onset of illness than
      BD-nonAUD patients. Logistic regression showed that the variables most strongly
      associated with a lifetime AUD diagnosis were SUD (non-alcohol), any substance
      misuse during the first mood episode, PTSD, male gender, suicide attempt, family
      history of SUD, and younger age at onset of BD. CONCLUSIONS: BD-AUD patients
      begin their mood disorder earlier and present more suicidal behaviors than BD
      nonAUD patients. Personal and family history of SUD may be good predictors of
      comorbid AUD among BD patients. These variables are easily assessed in the
      clinical setting and may help to identify a particularly severe subgroup of BD
      patients.

PMID- 24746529
TI  - The relationship between parental marital status and suicidal ideation and
      attempts by gender in adolescents: results from a nationally representative
      Korean sample.
AB  - OBJECTIVE: Suicide in adolescents is a major problem worldwide. The purpose of
      this study was to identify differences in suicidal behaviors with respect to
      parental marital status. METHODS: The data used in this study were obtained from
      the Korea Youth Risk Behavior Web-based Survey (KYRBWS) of middle and high school
      students in 2010. Using a national representative sample, this study analyzed
      data from 73,238 subjects. With respect to gender, the odds ratios of suicidal
      behavior were calculated based on the parental marital status, living situation,
      and family affluence scale (FAS). RESULTS: After adjusting for age, achievement,
      sadness, and substance use, the prevalence of suicidal ideation in adolescents
      with a remarried parent significantly increased among boys to 1.364 [95%
      confidence interval (CI)=1.027-1.813] and among girls to 1.511 (95% CI=1.215
      1.879). The odds ratio of suicide attempts increased to 1.808 (95% CI=1.119
      2.923) for adolescent boys and to 1.947 (95% CI=1.609-2.356) for adolescent
      girls. However, having a single parent did not affect the prevalence of suicidal
      ideation in either gender. In girls, as family affluence decreased, the odds
      ratio of suicidal ideation notably increased. For girls whose families were in a
      low tier of the FAS, the odds ratio of both suicidal ideation and suicide
      attempts increased. CONCLUSIONS: Both boys and girls were more likely to report
      suicidal ideation and attempts after a parent's remarriage, whereas family
      affluence was inversely related to suicidal ideation and attempts in girls.

PMID- 24746530
TI  - The Hypomania Checklist (HCL) - systematic review of its properties to screen for
      bipolar disorders.
AB  - OBJECTIVE: Bipolar disorders (BDs) are often not recognised with potentially
      drastic consequences for the individuals and their families. In clinical practice
      self-reports can be used to screen to enhance recognition. We therefore present a
      systematic review of the screening properties for the Hypomania Checklist (HCL
      32). METHODS: A systematic literature search was conducted to identify all
      relevant studies looking at the screening properties of the HCL-32 in adults.
      RESULTS: Out of 196 papers 21 papers reported data on 22 independent samples. We
      narratively reviewed these studies. Weighted estimated Sensitivity was 80%
      regardless of whether a BD diagnosis was compared to unipolar depression or any
      other non-bipolar diagnosis. Specificity indicated that the HCL-32 was better
      when comparing BD to unipolar depression (65.3%) than to any other diagnostic
      category (57.3%). Fewer studies provided estimates for predictive powers, leading
      to less reliable overall estimates for these indicators. CONCLUSIONS: Despite
      some limitations, using the HCL-32 as a first screening in patients seeking help
      for depression can be recommended, but should never be used on its own for
      diagnosing. Future research should examine whether screening properties can be
      improved by developing an algorithm incorporating the negative consequences
      reported for different areas in the HCL-32.

PMID- 24746531
TI  - The impact of mgrA on progression of Staphylococcus aureus sepsis.
AB  - Sepsis induced by Staphylococcus aureus has worse outcome with the appearance of
      methicillin-resistant Staphylococcus aureus (MRSA) because of multi-resistance to
      a large group of antibiotics, which may lead to death from septic shock.
      Pathogenesis of S. aureus infections are involved in the production of a wide
      variety of virulence factors. MgrA, a noval global regulator, is a member of the
      MarR (multiple antibiotic resistance regulator)/SarA (staphylococcal accessory
      regulator A) family proteins, which plays a key role in regulating the expression
      of major virulence factors in S. aureus. In the present study, by using a murine
      model of sepsis, we investigated the role of mgrA in onset and progression of S.
      aureus induced sepsis. We found that mice inoculated with wild-type strain Newman
      had significantly higher mortality (p = 0.029), more weight lost, more bacterial
      load in blood, spleen and kidney, more intense inflammation response, and worse
      histopathology than mice inoculated with mgrA knockout strain. Our results has
      provided evidence that mgrA is a global regulator in S. aureus, and play an
      important role in S. aureus sepsis, could increase mortality and accelerate the
      onset and development of sepsis. 

PMID- 24746532
TI  - Methodological requirement to analyze biomechanical postural control mechanisms
      with two platforms.
AB  - In 1996, Winter and colleagues proposed the existence of two postural control
      mechanisms in both the anteroposterior and mediolateral axes: a bodyweight
      (loading/unloading) distribution mechanism and a complementary center of pressure
      location mechanism. To measure the loading/unloading forces under each foot, the
      feet had to be placed side by side in the mediolateral axis and one foot ahead of
      the other in the anteroposterior axis. Our first objective was to reexamine the
      validity of anteroposterior data published with the feet side by side. In that
      foot condition, we expected no change in the anteroposterior loading/unloading
      forces (regardless of the task performed), and consequently no change in the
      complementary mechanism. Our second objective was to confirm our hypotheses with
      experimental data. Twelve healthy, young adults performed three types of body
      oscillation in the anteroposterior axis (at the hips, at the ankles and
      alternately at the ankles and hips) and a quiet stance condition with the feet
      side by side. As expected, the bodyweight mechanism did not vary significantly.
      Although the complementary mechanism was significantly higher in the ankle and
      alternating conditions, the change was very tiny (<0.3%). Thus, we propose
      methodological requirements to analyze both mechanisms. 

PMID- 24746533
TI  - Diabetic foot burns: a case series.
AB  - Burn injury in diabetic patients has been a recent topic of interest in published
      studies. Previous studies have shown increased complications in diabetic patients
      compared with nondiabetic controls who have sustained these injuries. A paucity
      of research has been devoted to foot-specific diabetic burn injury. We present a
      case series evaluating the mechanisms and complications of diabetic foot burns. 

PMID- 24746534
TI  - Kager's "Bermuda" Triangle.

PMID- 24746535
TI  - WITHDRAWN: Symptomatic Os Vesalianum Pedis: Long-Term Follow-Up of a Rare Entity
      in Childhood.
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- 24746536
TI  - A modified technique for flexor-to-extensor tendon transfer to correct residual
      metatarsophalangeal extension in the treatment of hammertoes.
AB  - A variety of surgical procedures exist for the correction of hammertoe
      deformities, and several different methods of flexor tendon transfer have been
      described for the correction of hammertoes associated with extension contracture
      of the corresponding metatarsophalangeal joint. In the present report, we have
      described a variation of flexor tendon tenodesis we have found useful. 

PMID- 24746537
TI  - Empirical Mode Decomposition of simulated and real ultrasonic Doppler signals of
      periodic fetal activity.
AB  - Simulated signals comprising components (trains of Gaussian packets) resulting
      from cardiac movements and from pseudorespiratory movements with added white
      noise were submitted to Empirical Mode Decomposition. The increase of sampling
      frequency fs (from 0.5 kHz to 5 kHz) for given signal to noise ratio SNR moves
      signal components toward higher order intrinsic mode functions (IMFs) and
      increases their number. The increase of the SNR (from -5 dB to 10 dB, fixed fs)
      moves the signal components to lower order IMFs. The separation of components is
      most efficient for SNR>=5 dB and fs not exceeding 1 kHz, for lower SNRs fs should
      be at least 2 kHz. SNR=infinity results in erroneous decomposition and therefore
      limited noise level is beneficial. Recommended number of sifting iterations is
      10. Fetal data obtained using 2 MHz emission frequency and sampled at 2 kHz were
      decomposed. The cardiac signal always appears in IMF3, frequently also in IMF1
      and IMF2. The pseudobreathing signal, appearing mainly in IMF4-6, is easy to
      separate. Signals resulting from fetal displacements due to maternal respiration
      appear in IMF7 or IMF8. The EMD performs better than the classic linear filtering
      as a tool for separation of the pseudorespiration signals and provides inferior
      results in terms of separation of the cardiac signals.

PMID- 24746538
TI  - Imaging in pulmonary hypertension: Focus on the role of echocardiography.
AB  - Patients with pulmonary hypertension must be evaluated using a multimodality
      approach to ensure a correct diagnosis and basal evaluation as well as a
      prognostic assessment. Beyond the assessment of pulmonary pressures, the
      echocardiographical examination allows the evaluation of right ventricular
      adaptation to elevated afterload. Numbers of variables are commonly used in the
      assessment of the pulmonary hypertension patient in order to detect changes in
      right heart geometry, right-to-left interaction and right ventricular
      dysfunction. Whereas an isolated change in one echocardiographical variable is
      not meaningful, multiple echocardiographical variable modifications together
      provide accurate information. In this review, we will link pulmonary hypertension
      pathophysiological changes with echocardiographical indices and describe the
      clinical implications of echocardiographical findings.

PMID- 24746539
TI  - Twenty-year differences in cardiovascular risk factor levels in a Swiss canton.

PMID- 24746540
TI  - Primary carnitine deficiency cardiomyopathy.

PMID- 24746541
TI  - Positive predictive values of 320-slice coronary computed tomography angiography
      with respect to multiple confounders in clinical routine.

PMID- 24746543
TI  - Mortality in patients requiring pacemaker implantation following transcatheter
      aortic valve replacement: insights from a systematic review and meta-analysis.

PMID- 24746542
TI  - Association of myeloperoxidase with total and cardiovascular mortality in
      individuals undergoing coronary angiography--the LURIC study.
AB  - BACKGROUND: The phagocytic enzyme myeloperoxidase (MPO) acts as a front-line
      defender against microorganisms. However, increased MPO levels have been found to
      be associated with complex and calcified atherosclerotic lesions and incident
      cardiovascular disease. Therefore, this study aimed to investigate a predictive
      role of MPO, a biomarker of inflammation and oxidative stress, for total and
      cardiovascular mortality in patients referred to coronary angiography. METHODS
      AND RESULTS: MPO plasma concentrations along with eight MPO polymorphisms were
      determined in 3036 participants of the Ludwigshafen Risk and Cardiovascular
      Health study (median follow-up 7.75 years). MPO concentrations were positively
      associated with age, diabetes, smoking, markers of systemic inflammation
      (interleukin-6, fibrinogen, C-reactive protein, serum amyloid A) and vascular
      damage (vascular cellular adhesion molecule-1 and intercellular adhesion molecule
      1) but negatively associated with HDL-cholesterol and apolipoprotein A-I. After
      adjustment for cardiovascular risk factors MPO concentrations in the highest
      versus the lowest quartile were associated with a 1.34-fold risk (95% CI: 1.09
      1.67) for total mortality. In the adjusted model the hazard ratio for
      cardiovascular mortality in the highest MPO quartile was 1.42 (95% CI: 1.07
      1.88). Five MPO polymorphisms were positively associated with MPO concentrations
      but not with mortality. Using Mendelian randomization, we did not obtain evidence
      for a causal association of MPO with either total or cardiovascular mortality.
      CONCLUSIONS: MPO concentrations but not genetic variants at the MPO locus are
      independently associated with risk for total and cardiovascular mortality in
      coronary artery disease patients.

PMID- 24746544
TI  - Supracardiac total anomalous pulmonary venous connection.

PMID- 24746545
TI  - Increased serum level of CTRP1 is associated with low coronary collateralization
      in stable angina patients with chronic total occlusion.

PMID- 24746546
TI  - Coalescence and fragmentation in the late Pleistocene archaeology of southernmost
      Africa.
AB  - The later Pleistocene archaeological record of southernmost Africa encompasses
      several Middle Stone Age industries and the transition to the Later Stone Age.
      Through this period various signs of complex human behaviour appear episodically,
      including elaborate lithic technologies, osseous technologies, ornaments, motifs
      and abstract designs. Here we explore the regional archaeological record using
      different components of lithic technological systems to track the transmission of
      cultural information and the extent of population interaction within and between
      different climatic regions. The data suggest a complex set of coalescent and
      fragmented relationships between populations in different climate regions through
      the late Pleistocene, with maximum interaction (coalescence) during MIS 4 and MIS
      2, and fragmentation during MIS 5 and MIS 3. Coalescent phases correlate with
      increases in the frequency of ornaments and other forms of symbolic expression,
      leading us to suggest that population interaction was a significant driver in
      their appearance. 

PMID- 24746547
TI  - Biomechanical strategies for accuracy and force generation during stone tool
      production.
AB  - Multiple hominin species used and produced stone tools, and the archaeological
      record provides evidence that stone tool behaviors intensified among later
      members of the genus Homo. This intensification is widely thought to be the
      product of cognitive and anatomical adaptations that enabled later Homo taxa to
      produce stone tools more efficiently relative to earlier hominin species. This
      study builds upon recent investigations of the knapping motions of modern humans
      to test whether aspects of our upper limb anatomy contribute to accuracy and/or
      efficiency. Knapping kinematics were captured from eight experienced knappers
      using a Vicon motion capture system. Each subject produced a series of Oldowan
      bifacial choppers under two conditions: with normal wrist mobility and while
      wearing a brace that reduced wrist extension (~30 degrees -35 degrees ),
      simulating one aspect of the likely primitive hominin condition. Under normal
      conditions, subjects employed a variant of the proximal-to-distal joint sequence
      common to throwing activities: subjects initiated down-swing upper limb motion at
      the shoulder and proceeded distally, increasing peak linear and angular
      velocities from the shoulder to the elbow to the wrist. At the wrist, subjects
      utilized the 'dart-thrower's arc,' the most stable plane of radiocarpal motion,
      during which wrist extension is coupled with radial deviation and flexion with
      ulnar deviation. With an unrestrained wrist, subjects achieved significantly
      greater target accuracy, wrist angular velocities, and hand linear velocities
      compared with the braced condition. Additionally, the modern wrist's ability to
      reach high degrees of extension (>=28.5 degrees ) following strike may decrease
      risk of carpal and ligamentous damage caused by hyperextension. These results
      suggest that wrist extension in humans contributes significantly to stone tool
      making performance. 

PMID- 24746548
TI  - Campus-based snack food vending consumption.
AB  - OBJECTIVE: To evaluate the purchases of university vending machine clientele and
      to understand what consumers purchase, purchase motivations, and purchase
      frequency after implementation of a vending policy designed to promote access to
      healthier snack options. METHODS: Cross-sectional data collection from consumers
      at 8 campus vending machines purposefully selected from a list of highest
      grossing machines. Vending machines were stocked with 28.5% green (choose most
      often), 43% yellow (occasionally), and 28.5% red (least often) food items.
      RESULTS: Consumers were predominately students (86%) and persons aged 18-24 years
      (71%). Red vending choices were overwhelmingly selected over healthier vending
      options (59%). Vended snack food selections were most influenced by hunger (42%)
      and convenience (41%). Most consumers (51%) frequented vending machines at least
      1 time per week. CONCLUSIONS AND IMPLICATIONS: Despite decreased access to less
      healthful red snack food choices, consumers chose these snacks more frequently
      than healthier options in campus vending machines.

PMID- 24746549
TI  - Differences in response to a dietary intervention between the general population
      and first-degree relatives of colorectal cancer patients.
AB  - OBJECTIVE: To determine whether response to a dietary intervention is greater
      among people with family history of colorectal cancer (CRC) compared with a
      general population. DESIGN: Cohort study examining participants from 2 related
      studies. SETTING: Rural Virginia. PARTICIPANTS: Seventy people with first-degree
      relatives with CRC and 113 participants from the intervention arm of a trial in
      the general population. INTERVENTION: Both studies implemented a low-intensity
      intervention delivered via telephone and mail, including low-literacy self-help
      booklets and personalized dietary feedback. MAIN OUTCOME MEASURES: Fat, fiber,
      and fruit and vegetable behavior. ANALYSIS: Propensity score matching controlled
      for confounders. Mixed-model ANOVAs compared samples; mediation by perceived
      cancer risk was assessed. RESULTS: Participants in both groups significantly
      improved fat, fiber, and fruit and vegetable behavior at 1-month follow-up; there
      was significantly greater improvement in the general population sample. Cancer
      risk perception did not mediate the relationship between study sample and dietary
      change. CONCLUSIONS AND IMPLICATIONS: Contrary to expectations, first-degree
      relatives of CRC patients did not respond better to a dietary intervention than
      the general population, nor was risk perception related to dietary change. Given
      the role of diet in CRC risk, additional research should investigate targeted
      strategies to improve dietary intakes of people at higher cancer risk.

PMID- 24746550
TI  - Event-related potentials to tones show differences between children with multiple
      risk factors for dyslexia and control children before the onset of formal reading
      instruction.
AB  - Multiple risk factors can affect the development of specific reading problems or
      dyslexia. In addition to the most prevalent and studied risk factor, phonological
      processing, auditory discrimination problems have also been found in children and
      adults with reading difficulties. The present study examined 37 children between
      the ages of 5 and 6, 11 of which had multiple risk factors for developing reading
      problems. The children participated in a passive oddball EEG experiment with
      sinusoidal sounds with changes in sound frequency, duration, or intensity. The
      responses to the standard stimuli showed a negative voltage shift in children at
      risk for reading problems compared to control children at 107-215 ms in
      frontocentral areas corresponding to P1 offset and N250 onset. Source analyses
      showed that the difference originated from the left and right auditory cortices.
      Additionally, the children at risk for reading problems had a larger late
      discriminative negativity (LDN) response in amplitude for sound frequency change
      than the control children. The amplitudes at the P1-N250 time window showed
      correlations to letter knowledge and phonological identification whereas the
      amplitudes at the LDN time window correlated with verbal short-term memory and
      rapid naming. These results support the view that problems in basic auditory
      processing abilities precede the onset of reading instruction and can act as one
      of the risk factors for dyslexia.

PMID- 24746551
TI  - Early clinical signs, lesion localization, and prognostic factors in unilateral
      symptomatic internal carotid artery occlusion.
AB  - BACKGROUND: The aim of this study was to assess infarct localization, clinical
      signs, and prognostic factors in cases with unilateral symptomatic total internal
      carotid occlusion. METHODS: In total, 101 patients who had a diagnosis of
      symptomatic unilateral carotid occlusion in the Department of Neurology, Trakya
      University Faculty of Medicine, between January 2008 and May 2012, were included
      in this study. The relationship between infarct localizations and prognosis of
      patients was evaluated by cranial magnetic resonance imaging (MRI) and diffusion
      weighted MRI. The condition of ipsilateral middle cerebral artery (MCA) and
      posterior communicating arteries (PCoAs) was assessed by cranial and cervical
      magnetic resonance angiography besides opposite carotid. Patients were evaluated
      by modified Rankin Scale in terms of prognosis at discharge and after 3 months.
      Furthermore, they were evaluated in terms of risk factors, such as cigarette and
      alcohol use, presence of temporary ischemic attack and stroke history,
      hypertension, diabetes mellitus, coronary artery disease, previous myocardial
      infarction, hyperlipidemia, and peripheral vascular disease. RESULTS: Territorial
      infarct was commonly seen as acute ischemic stroke pattern especially in cases
      with a poor MCA circulation and insufficient collateral circulation. Development
      of territorial stroke, occlusion of MCA, and nonvisualization of PCoA were found
      to be associated with poor prognosis. CONCLUSIONS: In unilateral symptomatic
      intracranial carotid artery occlusion, poor prognosis and high mortality
      associated territorial stroke pattern is frequently observed. Besides, presence
      of severe stenosis or occlusion and absence of collateral circulation in MCA are
      associated with poor prognosis.

PMID- 24746552
TI  - The immune receptor NOD1 and kinase RIP2 interact with bacterial peptidoglycan on
      early endosomes to promote autophagy and inflammatory signaling.
AB  - The intracellular innate immune receptor NOD1 detects Gram-negative bacterial
      peptidoglycan (PG) to induce autophagy and inflammatory responses in host cells.
      To date, the intracellular compartment in which PG is detected by NOD1 and
      whether NOD1 directly interacts with PG are two questions that remain to be
      resolved. To address this, we used outer membrane vesicles (OMVs) from pathogenic
      bacteria as a physiological mechanism to deliver PG into the host cell cytosol.
      We report that OMVs induced autophagosome formation and inflammatory IL-8
      responses in epithelial cells in a NOD1- and RIP2-dependent manner. PG contained
      within OMVs colocalized with both NOD1 and RIP2 in EEA1-positive early endosomes.
      Further, we provide evidence for direct interactions between NOD1 and PG.
      Collectively, these findings demonstrate that NOD1 detects PG within early
      endosomes, thereby promoting RIP2-dependent autophagy and inflammatory signaling
      in response to bacterial infection. 

PMID- 24746553
TI  - Accuracy of B-mode ultrasonography for diagnosing pregnancy and determination of
      fetal numbers in different breeds of goats.
AB  - A total of 150 does of different breeds were used to evaluate the accuracy of
      transrectal (TRU) and transabdominal ultrasonography (TAU) for pregnancy
      diagnosis and fetal number estimation and to study the effect of breed and age of
      goats on the accuracy of ultrasonography. All does were scanned by TRU at days 17
      22, 24-29 and 31-36 and by TAU at days 39-44 and 46-51 after breeding. The
      sensitivity (Se) of TRU for detecting pregnant does increased significantly
      (81.6% vs. 97.7%; P<0.0005) from days 17-22 to 24-29. There was a significant
      (P<0.05) effect of breed of goats on the specificity (Sp) of TAU for diagnosing
      non-pregnancy between days 39 and 51. In addition, there was a significant
      (P<0.01) effect of breed of goats on the Se and Sp of TRU for determination of
      does carrying multiples and singles, respectively, between days 24 and 36. The
      sensitivity of TAU for diagnosing pregnant does tended to be significantly
      (P=0.06) higher in young does (1.5-2 yr) than in older does (>2-9 yr) at days 39
      44. The accuracy of TRU for determination of does carrying singles was
      significantly (P<0.05) higher in young does than that in older ones at days 24
      29. In conclusions, TRU could be accurately used for early pregnancy diagnosis
      and fetal number estimation at days 24-29 and days 31-36, respectively, with
      accuracy similar to that of TAU at days 39-51. Furthermore, breed and age of does
      might influence the accuracy of ultrasonography for pregnancy diagnosis and fetal
      numbers estimation.

PMID- 24746554
TI  - Stage-dependent DAZL localization in stallion germ cells.
AB  - Deleted in azoospermia-like (DAZL) is used as a germ cell marker in several
      species, including mice, rats, pigs, rhesus monkeys, bulls, and humans. Our
      objectives with this study were to investigate DAZL expression in stallion germ
      cells by using immunofluorescence, immunocytochemistry, and western blotting, and
      to determine the effects of reproductive stage and breeding season on the DAZL
      positive cell population in seminiferous tubule cross sections. Testes were
      obtained during routine castration procedures at a large animal clinic and
      routine field service castration. The reproductive stage of the stallions was
      classified as pre-pubertal (<1 yr), pubertal (1-1.5 yr), post-pubertal (2-3 yr),
      or adult (4-8 yr). Using immunofluorescent staining, we showed that DAZL is
      localized to the cytoplasm of some, but not all, spermatogonia in pre-pubertal
      and pubertal horses. In the post-pubertal and adult testes, DAZL immunostaining
      was observed in spermatogonia proximal to the basement membrane of seminiferous
      tubules; however, few spermatogonia attached to the basement membrane were not
      immunolabeled. DAZL immunostaining was also observed in primary spermatocytes,
      but not in secondary spermatocytes, spermatids, or spermatozoa. DAZL protein was
      not detected in Leydig, Sertoli, or myoid cells of the testes at any reproductive
      stage. The immunocytochemistry analysis showed that DAZL immunolabeling was also
      localized to the cytoplasm of isolated germ cells such as spermatogonia or
      primary spermatocytes. We conclude that DAZL can be used as a marker of pre
      meiotic germ cells in stallions.

PMID- 24746555
TI  - What are the true values of the bending modulus of simple lipid bilayers?
AB  - Values of the bending modulus KC are reviewed, and possible causes for the
      considerable differences are discussed. One possible cause is the use of glucose
      and sucrose in the classical micromechanical manipulation and shape analysis
      methods. New data, using the more recent low angle X-ray method, are presented
      that do not support an effect of glucose or sucrose on KC. Another possible cause
      is using an incomplete theory to interpret the data. Adding a tilt term to the
      theory clearly does not affect the value obtained from the shape analysis method.
      It is shown that a tilt term, using a value of the modulus Ktheta indicated by
      simulations, theory, and estimated from order parameters obtained from NMR and
      from the wide angle X-ray method, should also not affect the value obtained using
      the micromechanical manipulation method, although it does require a small
      correction when determining the value of the area compressibility modulus KA. It
      is still being studied whether including a tilt term will significantly affect
      the values of KC obtained using low angle X-ray data. It remains unclear what
      causes the differences in the experimental values of KC for simple lipid
      bilayers. 

PMID- 24746556
TI  - Regulation of the Interleukin-6 gene expression during monocytic differentiation
      of HL-60 cells by chromatin remodeling and methylation.
AB  - The pro-inflammatory cytokine Interleukin (IL)-6 is involved in the proliferation
      and differentiation of leukocytes and non-immune cells, but its overproduction is
      associated with inflammatory and autoimmune disorders. The main producers of IL-6
      are mature monocytes, whereas progenitor cells and the promyeloid cell line HL-60
      do not synthesize IL-6. In contrast, HL-60 cells differentiated into monocytic
      cells were able to express IL-6 after lipopolysaccharide (LPS) stimulation. This
      study investigated the chromatin structure of the IL-6 promoter and the effect of
      methylation on IL-6 gene regulation during monopoiesis. The results show that the
      proximal IL-6 promoter regions I to III (+13/-329) were inaccessible in
      undifferentiated HL-60 cells but became significantly accessible in
      differentiated HL-60 cells stimulated with LPS. Region IL-6 VI (-1099/-1142)
      remained closed, but the upstream region IL-6 VII (-2564/-2877) relaxed after
      differentiation and LPS treatment. The opening of IL-6 IV (-309/-521) and IL-6V (
      500/-722), containing DNA and histone methylation sites, was differentiation
      dependent only. Demethylation experiments using 5-aza-2'-deoxycytidine (AZA)
      followed by LPS stimulation revealed a significant enhanced IL-6 mRNA expression
      and protein release by HL-60 cells. AZA treatment resulted in significant
      increased IL-6 promoter accessibilities, identifying methylation as an important
      repressor of IL-6 gene regulation in promyeloid cells. The histone deacetylase
      (HDAC) inhibitor trichostatin A (TSA) had no effect on IL-6 promoter
      accessibility. Our data indicate that during monopoiesis the proximal IL-6
      promoter is reorganized into an accessible conformation allowing transcription of
      IL-6 after LPS stimulation. DNA methylation appears to be the essential
      epigenetic mechanism in IL-6 gene expression of mature monocytes and their
      progenitors by controlling the chromatin structure. 

PMID- 24746557
TI  - Does tenofovir gel or do other microbicide products affect detection of
      biomarkers of semen exposure in vitro?
AB  - OBJECTIVES: There is currently no information on whether products evaluated in
      HIV microbicide trials affect the detection of the semen biomarkers prostate
      specific antigen (PSA) or Y chromosome DNA. STUDY DESIGN: We tested (in vitro)
      dilutions of tenofovir (TFV), UC781 and the hydroxyethylcellulose (HEC) placebo
      gels using the Abacus ABAcard and the quantitative (Abbott Architect total PSA)
      assays for PSA and Y chromosome DNA by real-time polymerase chain reaction.
      RESULTS: TFV gel and the HEC placebo adversely affected PSA detection using the
      ABAcard but not the Abbott Architect total PSA assay. UC781 adversely affected
      both the ABAcard and Abbott Architect total PSA assays. While there were some
      quantitative changes in the magnitude of the signal, none of the products
      affected positivity of the Y chromosome assay. CONCLUSIONS: The presence of TFV
      or HEC gels did not affect quantitative PSA or Y chromosome detection in vitro.
      Confirmation of these findings is recommended using specimens obtained following
      use of these gels in vivo. IMPLICATIONS: Researchers should consider the
      potential for specific microbicides or any products to affect the particular
      assay used for semen biomarker detection. The ABAcard assay for PSA detection
      should not be used with TFV UC781, or HEC.

PMID- 24746558
TI  - Detailed clinicopathological characteristics and possible lymphomagenesis of type
      II intestinal enteropathy-associated T-cell lymphoma in Japan.
AB  - Twenty-six Japanese cases of type II enteropathy-associated T-cell lymphoma
      (EATL) were examined. Multiple tumors throughout the small intestine were found
      in 15 patients (58%) and duodenal and colonic mucosal lesions in 8 and 6 cases,
      respectively. Histologically, intramucosal tumor spread and a zone of neoplastic
      intraepithelial lymphocytes (IELs) neighboring the main transmural tumors were
      detected in 20 (91%) and 17 (77%) of the 22 cases examined, respectively. Inside
      and outside the IEL zone, some degree of enteropathy with many reactive small
      IELs and villous atrophy was detected in 11 cases (50%). Immunohistologically,
      many CD56/CD8-positive small IELs were found in the enteropathic lesions of 4
      (36%) and 7 (64%) of these 11 cases. Lymphoma cells expressed tyrosine kinase
      receptor c-Met, serial phosphorylated (p)-mitogen-activated protein
      kinase/extracellular signal-regulated kinase, c-Myc, and Bcl2 in 18 (78%), 21
      (91%), 11 (42%), and 19 (73%) of the total cases, respectively. By fluorescence
      in situ hybridization, chromosomal loci 7q31 (c-Met) and 8q24 (c-Myc) were
      amplified in 11 (65%) and 12 (71%) of the 17 cases analyzed. Gain of 7q31 and c
      Met expression were significantly (P < .01) higher than in peripheral CD8
      positive T-cell or CD56-positive natural killer-cell lymphomas. Enteropathy was
      seen near the IEL zone in type II EATL, and activation of the c-Met, mitogen
      activated protein kinase/extracellular signal-regulated kinase-mitogen-activated
      protein kinase pathway, and c-Myc-Bcl2-mediated cell survival may play important
      roles in lymphomagenesis, converting enteropathy to type II EATL. Seven cases in
      the early clinical stages I and II-1 showed significantly (P < .01) better
      prognoses than did those in the advanced stages. Early detection of the mucosal
      lesions and tumors may improve patient prognosis. 

PMID- 24746559
TI  - Privileged diazepine compounds and their emergence as bromodomain inhibitors.
AB  - Chemical compounds built on a diazepine scaffold have recently emerged as potent
      inhibitors of the acetyl-lysine binding activity of bromodomain-containing
      proteins, which is required for gene transcriptional activation in cancer and
      inflammation. Not only have these chemical compounds validated bromodomains as
      attractive epigenetic drug targets, but they have also brought to the forefront
      another application of the diazepine, which had already been regarded as a
      versatile chemical scaffold in rational drug design. This article reviews the
      success of diazepine compounds as therapeutic agents and examines the unique
      chemical and geometric features of this privileged scaffold that make it an
      excellent template for developing potent and selective molecules that control
      bromodomain-related gene expression in human diseases. 

PMID- 24746560
TI  - Specificity and promiscuity at the branch point in gentamicin biosynthesis.
AB  - Gentamicin C complex is a mixture of aminoglycoside antibiotics used to treat
      severe Gram-negative bacterial infections. We report here key features of the
      late-stage biosynthesis of gentamicins. We show that the intermediate gentamicin
      X2, a known substrate for C-methylation at C-6' to form G418 catalyzed by the
      radical SAM-dependent enzyme GenK, may instead undergo oxidation at C-6' to form
      an aldehyde, catalyzed by the flavin-linked dehydrogenase GenQ. Surprisingly,
      GenQ acts in both branches of the pathway, likewise oxidizing G418 to an
      analogous ketone. Amination of these intermediates, catalyzed mainly by
      aminotransferase GenB1, produces the known intermediates JI-20A and JI-20B,
      respectively. Other pyridoxal phosphate-dependent enzymes (GenB3 and GenB4) act
      in enigmatic dehydroxylation steps that convert JI-20A and JI-20B into the
      gentamicin C complex or (GenB2) catalyze the epimerization of gentamicin C2a into
      gentamicin C2. 

PMID- 24746561
TI  - A crosslinker based on a tethered electrophile for mapping kinase-substrate
      networks.
AB  - Despite the continuing progress made toward mapping kinase signaling networks,
      there are still many phosphorylation events for which the responsible kinase has
      not yet been identified. We are interested in addressing this problem through
      forming covalent crosslinks between a peptide substrate and the corresponding
      phosphorylating kinase. Previously we reported a dialdehyde-based kinase-binding
      probe capable of such a reaction with a peptide containing a cysteine substituted
      for the phosphorylatable ser/thr/tyr residue. Here, we examine the yield of a
      previously reported dialdehyde-based probe and report that the dialdehyde-based
      probes possess a significant limitation in terms of crosslinked kinase-substrate
      product yield. To address this limitation, we developed a crosslinking scheme
      based on a kinase activity-based probe, and this crosslinker provides an increase
      in efficiency and substrate specificity, including in the context of cell lysate.

PMID- 24746562
TI  - Small molecule drug A-769662 and AMP synergistically activate naive AMPK
      independent of upstream kinase signaling.
AB  - The AMP-activated protein kinase (AMPK) is a metabolic stress-sensing
      alphabetagamma heterotrimer responsible for energy homeostasis, making it a
      therapeutic target for metabolic diseases such as type 2 diabetes and obesity.
      AMPK signaling is triggered by phosphorylation on the AMPK alpha subunit
      activation loop Thr172 by upstream kinases. Dephosphorylated, naive AMPK is
      thought to be catalytically inactive and insensitive to allosteric regulation by
      AMP and direct AMPK-activating drugs such as A-769662. Here we show that A-769662
      activates AMPK independently of alpha-Thr172 phosphorylation, provided beta
      Ser108 is phosphorylated. Although neither A-769662 nor AMP individually
      stimulate the activity of dephosphorylated AMPK, together they stimulate >1,000
      fold, bypassing the requirement for beta-Ser108 phosphorylation. Consequently A
      769662 and AMP together activate naive AMPK entirely allosterically and
      independently of upstream kinase signaling. These findings have important
      implications for development of AMPK-targeting therapeutics and point to possible
      combinatorial therapeutic strategies based on AMP and AMPK drugs. 

PMID- 24746563
TI  - Intrafractional tracking accuracy in infrared marker-based hybrid dynamic tumour
      tracking irradiation with a gimballed linac.
AB  - PURPOSE: To verify the intrafractional tracking accuracy in infrared (IR) marker
      based hybrid dynamic tumour tracking irradiation ("IR Tracking") with the
      Vero4DRT. MATERIALS AND METHODS: The gimballed X-ray head tracks a moving target
      by predicting its future position from displacements of IR markers in real-time.
      Ten lung cancer patients who underwent IR Tracking were enrolled. The 95th
      percentiles of intrafractional mechanical (iEM(95)), prediction (iEP(95)), and
      overall targeting errors (iET(95)) were calculated from orthogonal fluoroscopy
      images acquired during tracking irradiation and from the synchronously acquired
      log files. RESULTS: Averaged intrafractional errors were (left-right, cranio
      caudal [CC], anterior-posterior [AP])=(0.1mm, 0.4mm, 0.1mm) for iEM(95), (1.2mm,
      2.7mm, 2.1mm) for iEP(95), and (1.3mm, 2.4mm, 1.4mm) for iET(95). By correcting
      systematic prediction errors in the previous field, the iEP(95) was reduced
      significantly, by an average of 0.4mm in the CC (p<0.05) and by 0.3mm in the AP
      (p<0.01) directions. CONCLUSIONS: Prediction errors were the primary cause of
      overall targeting errors, whereas mechanical errors were negligible. Furthermore,
      improvement of the prediction accuracy could be achieved by correcting systematic
      prediction errors in the previous field.

PMID- 24746564
TI  - Changes in mast cell number and stem cell factor expression in human skin after
      radiotherapy for breast cancer.
AB  - BACKGROUND AND PURPOSE: Mast cells are involved in the pathogenesis of radiation
      fibrosis and may be a therapeutic target. The mechanism of increased mast cell
      number in relation to acute and late tissue responses in human skin was
      investigated. MATERIALS AND METHODS: Punch biopsies of skin 1 and 15-18 months
      after breast radiotherapy and a contralateral control biopsy were collected. Mast
      cells were quantified by immunohistochemistry using the markers c-Kit and
      tryptase. Stem cell factor (SCF) and collagen-1 expression was analysed by qRT
      PCR. Clinical photographic scores were performed at post-surgical baseline and 18
      months and 5 years post-radiotherapy. Primary human dermal microvascular
      endothelial cell (HDMEC) cultures were exposed to 2Gy ionising radiation and p53
      and SCF expression was analysed by Western blotting and ELISA. RESULTS: Dermal
      mast cell numbers were increased at 1 (p=0.047) and 18 months (p=0.040) using c
      Kit, and at 18 months (p=0.024) using tryptase immunostaining. Collagen-1 mRNA in
      skin was increased at 1 month (p=0.047) and 18 months (p=0.032) and SCF mRNA
      increased at 1 month (p=0.003). None of 16 cases scored had a change in
      photographic appearance at 5 years, compared to baseline. SCF expression was not
      increased in HDMECs irradiated in vitro. CONCLUSIONS: Increased mast cell number
      was associated with up-regulated collagen-1 expression in human skin at early and
      late time points. This increase could be secondary to elevated SCF expression at
      1 month after radiotherapy. Although mast cells accumulate around blood vessels,
      no endothelial cell secretion of SCF was seen after in vitro irradiation.
      Modification of mast cell number and collagen-1 expression may be observed in
      skin at 1 and 18 months after radiotherapy in breast cancer patients with no
      change in photographic breast appearance at 5 years.

PMID- 24746565
TI  - Even low doses of radiation lead to DNA damage accumulation in lung tissue
      according to the genetically-defined DNA repair capacity.
AB  - BACKGROUND AND PURPOSE: Intensity-modulated radiation therapy for thoracic
      malignancies increases the exposure of healthy lung tissue to low-dose radiation.
      The biological impact of repetitive low-dose radiation on the radiosensitive lung
      is unclear. MATERIALS AND METHODS: In the present study, using mouse strains with
      different genetic DNA repair capacities, we monitored the extent of DNA damage in
      lung parenchyma after 2, 4, 6, 8, and 10weeks of daily low-dose 100-mGy
      radiation. RESULTS: Using 53BP1 as a marker for double-strand breaks, we observed
      DNA damage accumulation during fractionated low-dose radiation with increasing
      cumulative doses. The amount of radiation-induced 53BP1 varied significantly
      between bronchiolar and alveolar epithelial cells, suggesting that different cell
      populations in the lung parenchyma had varying vulnerabilities to ionizing
      radiation. The genetic background of DNA repair determined the extent of
      cumulative low-dose radiation damage. Moreover, increased DNA damage during
      fractionated low-dose radiation affected replication, and apoptosis in the lung
      parenchyma, which may influence overall lung function. CONCLUSION: Collectively,
      our results suggest that low, yet damaging, doses of radiation increase the risk
      of toxicity to normal lung tissue and the probability of developing secondary
      malignancies.

PMID- 24746566
TI  - Genetic variants in inducible nitric oxide synthase gene are associated with the
      risk of radiation-induced lung injury in lung cancer patients receiving
      definitive thoracic radiation.
AB  - BACKGROUND AND PURPOSE: Nitric oxide (NO), mainly synthesized by inducible nitric
      oxide synthase (NOS2) in pathological conditions, plays an important role in
      cytotoxicity, inflammation and fibrosis. Elevations in exhaled NO after thoracic
      radiation have been reported to predict radiation-induced lung injury (RILI).
      This study examined whether genetic variations in NOS2 gene is associated with
      the risk of RILI. MATERIAL AND METHODS: A cohort of 301 patients between 2009 and
      2011 were genotyped for 21 single nucleotide polymorphisms (SNPs) in the NOS2
      gene by the Sequenom MassArray system. Kaplan-Meier cumulative probability was
      used to assess RILI risk and Cox proportional hazards analyses were performed to
      evaluate the effect of NOS2 genotypes on RILI. RESULTS: Multivariate analysis
      found that three SNPs (rs2297518, rs1137933 and rs16949) in NOS2 were
      significantly associated with risk of RILI?2 (P value=0.001, 0.000092, 0.001,
      respectively) after adjusting for other covariates. Their associations were
      independent of radiation dose and mean lung dose. Further haplotype analysis
      indicated that the ATC haplotype of three SNPs is associated with reducing the
      risk of developing RILI. CONCLUSION: Our results demonstrate that genetic
      variants of NOS2 may serve as a reliable predictor of RILI in lung cancer
      patients treated with thoracic radiation.

PMID- 24746567
TI  - A dosimetric study of polyethylene glycol hydrogel in 200 prostate cancer
      patients treated with high-dose rate brachytherapy+/-intensity modulated
      radiation therapy.
AB  - BACKGROUND AND PURPOSE: We sought to analyze the effect of polyethylene glycol
      (PEG) hydrogel on rectal doses in prostate cancer patients undergoing
      radiotherapy. MATERIALS AND METHODS: Between July 2009 and April 2013, we treated
      200 clinically localized prostate cancer patients with high-dose rate (HDR)
      brachytherapy+/-intensity modulated radiation therapy. Half of the patients
      received a transrectal ultrasound (TRUS)-guided transperineal injection of 10mL
      PEG hydrogel (DuraSealTM Spinal Sealant System; Covidien, Mansfield, MA) in their
      anterior perirectal fat immediately prior to the first HDR brachytherapy
      treatment and 5mL PEG hydrogel prior to the second HDR brachytherapy treatment.
      Prostate, rectal, and bladder doses and prostate-rectal distances were calculated
      based upon treatment planning CT scans. RESULTS: There was a success rate of 100%
      (100/100) with PEG hydrogel implantation. PEG hydrogel significantly increased
      the prostate-rectal separation (mean+/-SD, 12+/-4mm with gel vs. 4+/-2mm without
      gel, p<0.001) and significantly decreased the mean rectal D2 mL (47+/-9% with gel
      vs. 60+/-8% without gel, p<0.001). Gel decreased rectal doses regardless of body
      mass index (BMI). CONCLUSIONS: PEG hydrogel temporarily displaced the rectum away
      from the prostate by an average of 12mm and led to a significant reduction in
      rectal radiation doses, regardless of BMI.

PMID- 24746568
TI  - Four-dimensional treatment planning in layer-stacking boost irradiation for
      carbon-ion pancreatic therapy.
AB  - PURPOSE: We evaluated respiratory-gated carbon-ion beam dose distribution with
      boost irradiation in pancreatic therapy and compared results between the passive
      scattering and layer-stacking (a kind of semi-active scanning) irradiation
      techniques. MATERIALS AND METHODS: A total of 21 patients who were treated with
      conventional passive carbon-ion beam for pancreatic cancer underwent 4DCT imaging
      under free-breathing conditions. We defined two types of clinical target volume
      (CTV) for the initial and boost irradiations: CTV1 included the gross tumor
      volume (GTV) and peripheral organs, and CTV2 included the GTV only with an added
      uniform 2-mm margin. Planning target volumes 1 and 2 (PTV1 and PTV2) were
      calculated by adding the range variation considered internal margin defined by
      4DCT to the respective CTVs. The initial prescribed dose (=45.6Gy (RBE); RBE
      weighted absorbed dose) was given to PTV1, and the boost dose was increased up to
      26.4Gy (RBE) and given to PTV2. Dose assessments were compared between
      irradiation techniques using the paired t-test. RESULTS: D95 (GTV, CTV2) values
      were increased from 44.2Gy (RBE) with the prescribed dose of 45.6Gy (RBE) to
      69.8Gy (RBE) with the prescribed dose of 72.0Gy (RBE) with both irradiations.
      Layer-stacking irradiation reduced excessive dosing to normal tissues compared
      with passive scattering irradiation, particularly for boost irradiation. 1st-2nd
      portion V20/V40, and stomach V20 values up to the prescribed dose of 48.0, 60.0,
      and 52.8Gy (RBE) were smaller than those in passive scattering irradiation
      without boost. Kidney V15/V30 (0.6% (P=0.05)/0.1% (P>0.20) for right kidney,
      10.4% (P<0.01)/3.2% (P<0.01) for left kidney), pancreas V20/V40 (88.6%
      (P<0.01)/83.0% (P<0.03)), duodenum 3rd-4th portion V20/V40 (23.6% (P<0.01)/9.5%
      (P>0.06)), and stomach V20 (16.3% (P<0.01)) values in layer-stacking irradiation
      were smaller than those in passive scattering irradiation up to the prescribed
      dose of 72.0Gy (RBE) and also smaller than those with passive scattering
      irradiation without boost irradiation (=45.6Gy (RBE)). CONCLUSION: In pancreatic
      particle beam therapy, delivery of the prescribed dose by layer-stacking boost
      irradiation provides a greater reduction in excessive dose to normal tissues than
      delivery by passive scattering irradiation.

PMID- 24746569
TI  - Blood biomarkers are helpful in the prediction of response to chemoradiation in
      rectal cancer: a prospective, hypothesis driven study on patients with locally
      advanced rectal cancer.
AB  - PURPOSE/OBJECTIVE: Chemoradiation (CRT) has been shown to lead to downsizing of
      an important portion of rectal cancers. In order to tailor treatment at an
      earlier stage during treatment, predictive models are being developed. Adding
      blood biomarkers may be attractive for prediction, as they can be collected very
      easily and determined with excellent reproducibility in clinical practice. The
      hypothesis of this study was that blood biomarkers related to tumor load, hypoxia
      and inflammation can help to predict response to CRT in rectal cancer.
      MATERIAL/METHODS: 295 patients with locally advanced rectal cancer who were
      planned to undergo CRT were prospectively entered into a biobank protocol
      (NCT01067872). Blood samples were drawn before start of CRT. Nine biomarkers were
      selected, based on a previously defined hypothesis, and measured in a
      standardized way by a certified lab: CEA, CA19-9, LDH, CRP, IL-6, IL-8, CA IX,
      osteopontin and 25-OH-vitamin D. Outcome was analyzed in two ways: pCR vs. non
      pCR and responders (defined as ypT0-2N0) vs. non-responders (all other ypTN
      stages). RESULTS: 276 patients could be analyzed. 20.7% developed a pCR and 47.1%
      were classified as responders. In univariate analysis CEA (p=0.001) and
      osteopontin (p=0.012) were significant predictors for pCR. Taking response as
      outcome CEA (p<0.001), IL-8 (p<0.001) and osteopontin (p=0.004) were significant
      predictors. In multivariate analysis CEA was the strongest predictor for pCR (OR
      0.92, p=0.019) and CEA and IL-8 predicted for response (OR 0.97, p=0.029 and OR
      0.94, p=0.036). The model based on biomarkers only had an AUC of 0.65 for pCR and
      0.68 for response; the strongest model included clinical data, PET-data and
      biomarkers and had an AUC of 0.81 for pCR and 0.78 for response. CONCLUSION: CEA
      and IL-8 were identified as predictive biomarkers for tumor response and PCR
      after CRT in rectal cancer. Incorporation of these blood biomarkers leads to an
      additional accuracy of earlier developed prediction models using clinical
      variables and PET-information. The new model could help to an early adaptation of
      treatment in rectal cancer patients.

PMID- 24746570
TI  - Patient reported outcome measures (PROMs) following forward planned field-in
      field IMRT: results from the Cambridge Breast IMRT trial.
AB  - BACKGROUND: The use of intensity-modulated radiotherapy (IMRT) in breast cancer
      reduces clinician-assessed breast tissue toxicity including fibrosis,
      telangectasia and sub-optimal cosmesis. Patient reported outcome measures (PROMs)
      are also important as they provide the patient's perspective. This longitudinal
      study reports on (a) the effect of forward planned field-in-field IMRT (~simple
      IMRT) on PROMs compared to standard RT at 5 years after RT, (b) factors affecting
      PROMs at 5years after RT and (c) the trend of PROMs over 5 years of follow up.
      METHODS: PROMs were assessed at baseline (pre-RT), 6, 24 and 60 months after
      completion of RT using global health (EORTC QLQ C30) and 4 breast symptom
      questions (BR23). Also, 4 breast RT-specific questions were included at 6, 24 and
      60 months: change in skin appearance, firmness to touch, reduction in breast size
      and overall change in breast appearance since RT. The benefits of simple IMRT
      over standard RT at 5 years after RT were assessed using standard t-test for
      global health and logistic regression analysis for breast symptom questions and
      breast RT-specific questions. Clinical factors affecting PROMs at 5 years were
      investigated using a multivariate analysis. A repeated mixed model was applied to
      explore the trend over time for each of PROMs. RESULTS: (89%) 727/815, 84%, 81%
      and 61% patients completed questionnaires at baseline, 6, 24 and 60 months
      respectively. Patients reported worse toxicity for all four BR23 breast symptoms
      at 6 months, which then improved over time (p<0.0001). They also reported
      improvement in skin appearance and breast hardness over time (p<0.0001), with no
      significant change for breast shrinkage (p=0.47) and overall breast appearance
      (p=0.13). At 5years, PROMs assessments did not demonstrate a benefit for simple
      IMRT over standard radiotherapy. Large breast volume, young age, baseline
      surgical cosmesis and post-operative infection were the most important variables
      to affect PROMs. CONCLUSIONS: This study was unable to demonstrate the benefits
      of IMRT on PROMs at 5years. PROMs are influenced by non-radiotherapy factors and
      surgical factors should be optimised to improve patients' outcome. Only a small
      proportion of patients report moderate-severe breast changes post radiotherapy,
      with most PROMs improving over time. The difference in clinician assessment and
      PROMs outcome requires further investigation.

PMID- 24746571
TI  - Retrograde superselective intra-arterial chemotherapy and daily concurrent
      radiotherapy for stage III and IV oral cancer: analysis of therapeutic results in
      112 cases.
AB  - PURPOSE: To evaluate the therapeutic results and rate of organ preservation in
      patients with stage III or IV oral cancer treated with retrograde superselective
      intra-arterial chemotherapy and daily concurrent radiotherapy. MATERIALS AND
      METHODS: One hundred and twelve patients with stage III and IV oral squamous cell
      carcinoma underwent intra-arterial chemoradiotherapy. Catheterization from the
      superficial temporal and occipital arteries was performed. Treatment consisted of
      superselective intra-arterial chemotherapy (docetaxel, total 60mg/m(2),
      cisplatin, total 150mg/m(2)) and daily concurrent radiotherapy (total of 60Gy)
      for 6 weeks. RESULTS: The median follow-up for all patients was 46.2 months
      (range, 10-76 months). After intra-arterial chemoradiotherapy, primary site
      complete response was achieved in 98 (87.5%) of 112 cases. Five-year survival and
      local control rates were 71.3% and 79.3%, respectively. Grade 3 or 4 toxicities
      included mucositis in 92.0%, neutropenia in 30.4%, dermatitis in 28.6%, anemia in
      26.8%, and thrombocytopenia in 7.1% of patients. Grade 3 toxicities included
      dysphagia in 72.3%, nausea/vomiting in 21.4%, fever in 8.0%, and renal failure in
      0.9% of patients. CONCLUSION: Retrograde superselective intra-arterial
      chemotherapy and daily concurrent radiotherapy for stage III and IV oral cancer
      provided good overall survival and local control.

PMID- 24746572
TI  - A simulation framework for modeling tumor control probability in breast
      conserving therapy.
AB  - BACKGROUND AND PURPOSE: Microscopic disease (MSD) left after tumorectomy is a
      major cause of local recurrence in breast conserving therapy (BCT). However, the
      effect of microscopic disease and RT dose on tumor control probability (TCP) was
      seldom studied quantitatively. A simulation framework was therefore constructed
      to explore the relationship between tumor load, radiation dose and TCP. MATERIALS
      AND METHODS: First, we modeled total disease load and microscopic spread with a
      pathology dataset. Then we estimated the remaining disease load after tumorectomy
      through surgery simulation. The Webb-Nahum TCP model was extended by clonogenic
      cell fraction to model the risk of local recurrence. The model parameters were
      estimated by fitting the simulated results to the observations in two clinical
      trials. RESULTS: Higher histopathology grade has a strong correlation with larger
      MSD cell quantity. On average 12.5% of the MSD cells remained in the patient's
      breast after surgery but varied considerably among patients (0-100%);
      illustrating the role of radiotherapy. A small clonogenic cell fraction was
      optimal in our model (one in every 2.7*10(6)cells). The mean radiosensitivity was
      estimated at 0.067Gy(-1) with standard deviation of 0.022Gy(-1). CONCLUSION: A
      relationship between radiation dose and TCP was established in a newly designed
      simulation framework with detailed disease load, surgery and radiotherapy models.

PMID- 24746573
TI  - Anxiety and its time courses during radiotherapy for non-metastatic breast
      cancer: a longitudinal study.
AB  - PURPOSE: To our knowledge, no study has specifically assessed the time course of
      anxiety during radiotherapy (RT). The objective of this study was to assess
      anxiety time courses in patients with non-metastatic breast cancer. MATERIAL AND
      METHODS: This multicenter, descriptive longitudinal study included 213
      consecutive patients with breast cancer who completed visual analog scales (VASs)
      assessing state anxiety before and after the RT simulation and the first and last
      five RT sessions. RESULTS: Pre- and post-session anxiety mean levels were highest
      at the RT simulation (respectively, 2.9+/-2.9 and 1.6+/-2.5) and first RT session
      (respectively, 3.4+/-2.9 and 2.0+/-2.4), then declined rapidly. Clinically
      relevant mean differences (?1cm on the VAS) between pre- and post
      simulation/session VAS scores were found only for the RT simulation (-1.3+/-2.7;
      p<0.001) and first RT session (-1.4+/-2.4; p<0.001). Five percent to 16% of
      patients presented clinically relevant anxiety (pre- and post-simulation/session
      VAS scores?4cm) throughout treatment. CONCLUSIONS: To optimize care, RT team
      members should offer all patients appropriate information about treatment at the
      simulation, check patients' understanding, and identify patients with clinically
      relevant anxiety requiring appropriate support throughout RT.

PMID- 24746574
TI  - C646, a selective small molecule inhibitor of histone acetyltransferase p300,
      radiosensitizes lung cancer cells by enhancing mitotic catastrophe.
AB  - BACKGROUND AND PURPOSE: Chromatin remodeling through histone modifications,
      including acetylation, plays an important role in the appropriate response to DNA
      damage induced by ionizing radiation (IR). Here we investigated the
      radiosensitizing effect of C646, a selective small molecule inhibitor of p300
      histone acetyltransferase, and explored the underlying mechanisms. MATERIALS AND
      METHODS: A549, H157 and H460 human non-small cell lung carcinoma (NSCLC) cells,
      and HFL-III human lung fibroblasts were assessed by clonogenic survival assay.
      Apoptosis and necrosis were assessed by annexin V staining. Senescence was
      assessed by Senescence-associated beta-galactosidase staining. Mitotic
      catastrophe was assessed by evaluating nuclear morphology with DAPI staining.
      Cell cycle profiles were analyzed by flow cytometry. Protein expression was
      analyzed by immunoblotting. RESULTS: C646 sensitized A549, H460 and H157 cells to
      IR with a dose enhancement ratio at 10% surviving fraction of 1.4, 1.2 and 1.2,
      respectively. C646 did not radiosensitize HFL-III cells. In A549 cells, but not
      in HFL-III cells, C646 (i) enhanced mitotic catastrophe but not apoptosis,
      necrosis, or senescence after IR; (ii) increased the hyperploid cell population
      after IR; and (iii) suppressed the phosphorylation of CHK1 after IR. CONCLUSIONS:
      C646 radiosensitizes NSCLC cells by enhancing mitotic catastrophe through the
      abrogation of G2 checkpoint maintenance.

PMID- 24746575
TI  - Comparative dosimetry of three-phase adaptive and non-adaptive dose-painting IMRT
      for head-and-neck cancer.
AB  - PURPOSE: The anatomical changes, which occur during the radiotherapy treatment
      for head-and-neck cancer, may compromise the effectiveness of the treatment. This
      study compares dosimetrical effects of adaptive (ART) and non-adaptive (RT) dose
      painted radiotherapy. MATERIALS AND METHODS: For 10 patients, three treatment
      phases were preceded by a planning PET/CT scan. In ART, phases II and III were
      planned using PET/CT2 and PET/CT3, respectively. In RT, phases II and III were
      planned on PET/CT1 and recalculated on PET/CT2 and PET/CT3. Deformable image co
      registration was used to sum the dose distributions and to propagate regions-of
      interest (ROIs) drawn on PET/CT1 to PET/CT2, PET/CT3 and a last-treatment-day CT
      scan. RESULTS: Re-adjusted dose-painting ART provided higher minimum and lower
      maximum doses in target ROIs in comparison to RT. On average, ART reduced the
      parotids' median dose and swallowing structures mean dose by 4.6-7.1% (p>0.05)
      and 3% (p=0.06), respectively. Dose differences for targets were from -1.6% to
      6.6% and for organs-at-risk from -7.1% to 7.1%. Analysis of individual patient
      data showed large improvements of ROI dose/volume metrics by ART, reaching a
      24.4% minimum-dose increase in the elective neck planning target volume and 21.1%
      median-dose decrease in swallowing structures. CONCLUSION: Compared to RT, ART
      readjusts dose-painting, increases minimum and decreases maximum doses in target
      volumes and improves dose/volume metrics of organs-at-risk. The results favored
      the adaptive strategy, but also revealed considerable heterogeneity in patient
      specific benefit. Reporting population-average effects underestimates the patient
      specific benefits of ART.

PMID- 24746576
TI  - Evaluating the role of mitochondrial DNA variation to the genetic predisposition
      to radiation-induced toxicity.
AB  - BACKGROUND AND PURPOSE: Mitochondrial DNA common variants have been reported to
      be associated with the development of radiation-induced toxicity. Using a large
      cohort of patients, we aimed to validate these findings by investigating the
      potential role of common European mitochondrial DNA SNPs (mtSNPs) to the
      development of radio-toxicity. MATERIAL AND METHODS: Overall acute and late
      toxicity data were assessed in a cohort of 606 prostate cancer patients by means
      of Standardized Total Average Toxicity (STAT) score. We carried out association
      tests between radiation toxicity and a selection of 15 mtSNPs (and the
      haplogroups defined by them). RESULTS: Statistically significant association
      between mtSNPs and haplogroups with toxicity could not be validated in our
      Spanish cohort. CONCLUSIONS: The present study suggests that the mtDNA common
      variants analyzed are not associated with clinically relevant increases in risk
      of overall radiation-induced toxicity in prostate cancer patients.

PMID- 24746577
TI  - MRI-based tumor motion characterization and gating schemes for radiation therapy
      of pancreatic cancer.
AB  - BACKGROUND AND PURPOSE: To characterize pancreatic tumor motion and to develop a
      gating scheme for radiotherapy in pancreatic cancer. MATERIALS AND METHODS: Two
      cine MRIs of 60s each were performed in fifteen pancreatic cancer patients, one
      in sagittal direction and one in coronal direction. A Minimum Output Sum of
      Squared Error (MOSSE) adaptive correlation filter was used to quantify tumor
      motion in craniocaudal, lateral and anteroposterior directions. To develop a
      gating scheme, stability of the breathing phases was examined and a gating window
      assessment was created, incorporating tumor motion, treatment time and motion
      margins. RESULTS: The largest tumor motion was found in craniocaudal direction,
      with an average peak-to-peak amplitude of 15mm (range 6-34mm). Amplitude of the
      tumor in the anteroposterior direction was on average 5mm (range 1-13mm). The
      least motion was seen in lateral direction (average 3mm, range 2-5mm). The end
      exhale position was the most stable position in the breathing cycle and tumors
      spent more time closer to the end exhale position than to the end inhale
      position. On average, a margin of 25% of the maximum craniocaudal breathing
      amplitude was needed to achieve full target coverage with a duty cycle of 50%.
      When reducing the duty cycle to 50%, a margin of 5mm was sufficient to cover the
      target in 11 out of 15 patients. CONCLUSION: Gated delivery for radiotherapy of
      pancreatic cancer is best performed around the end exhale position as this is the
      most stable position in the breathing cycle. Considerable margin reduction can be
      established at moderate duty cycles, yielding acceptable treatment efficiency.
      However, motion patterns and amplitude do substantially differ between individual
      patients. Therefore, individual treatment strategies should be considered for
      radiotherapy in pancreatic cancer.

PMID- 24746579
TI  - Radiation therapy: a major factor in the five-year survival analysis of women
      with breast cancer in Lagos, Nigeria.
AB  - PURPOSE: This retrospective study was carried out to examine five-year survival
      from breast cancer cases diagnosed between 2005 and May 2008 in Nigerian women.
      MATERIAL AND METHODS: Two hundred and twenty-four patients were entered into the
      study. Five-year survival was evaluated using proportional hazard model proposed
      by Cox to assess variables such as age of diagnosis, menopausal status, and stage
      of the disease in the two treatment groups: surgery/chemotherapy or
      surgery/chemotherapy/radiotherapy. RESULTS: Findings revealed that the different
      staging of disease and treatment are independent predictors of disease outcome
      whereas age of diagnosis and menopausal status although associated with low
      hazards, are not significant. TNM Stage I (Hazard Ratio=0.153, 95% CI 0.45-0.51,
      P=0.003), II (Hazard Ratio=0.245, 95% CI 0.12-0.46, P=0.0001), and III (Hazard
      Ratio=0.449, 95% CI 0.31-0.46, P=0.0001) showed significantly greater survival
      rates compared to TNM Stage IV for patients receiving surgery/chemotherapy.
      Similarly, for patients receiving surgery/chemotherapy/radiotherapy TNM Stage II
      (Hazard Ratio=0.110, 95% CI 0.02-0.46, P=0.003) and III (Hazard Ratio=0.238, 95%
      CI 0.07-0.73, P=0.012) also showed significantly greater survival rates compared
      to TNM Stage IV. Treatment had a significant impact on survival independent of
      stage, age, and menopausal status. Patients receiving
      surgery/chemotherapy/radiotherapy had a significant increase in survival outcome
      for TNM Stage (II, P=0.045; III, P=0.0001); age groups (40-49, P=0.021; 50-59,
      P=0.016; 60-69, P=0.017; >70, P=0.025); and menopausal status (premenopausal,
      P=0.049; postmenopausal, P=0.0001) compared to those receiving
      surgery/chemotherapy. CONCLUSION: The five-year breast cancer survival rate in
      Lagos, Nigeria 24.1% (54/224) is relatively poor compared to most countries in
      the world and needs to be improved. Poor survival rates are mainly attributed to
      late presentation and poor follow-up, hence early detection through breast cancer
      awareness programs, appropriate logistics and better management of patients
      through guidelines for the treatment of breast need to be implemented to improve
      survival.

PMID- 24746578
TI  - Does a central review platform improve the quality of radiotherapy for rectal
      cancer? Results of a national quality assurance project.
AB  - BACKGROUND AND PURPOSE: Quality assurance (QA) for radiation treatment has become
      a priority since poorly delivered radiotherapy can negatively influence patient
      outcome. Within a national project we evaluated the feasibility of a central
      review platform and its role in improving uniformity of clinical target volume
      (CTV) delineation in daily practice. MATERIAL AND METHODS: All Belgian
      radiotherapy departments were invited to participate and were asked to upload
      CTVs for rectal cancer treatment onto a secured server. These were centrally
      reviewed and feedback was given per e-mail. For each five consecutive patients
      per centre, the overlap parameter dice coefficient (DC) and the volumetric
      parameters volumetric ratio (RV) and commonly contoured volume (VCC) were
      calculated. RESULTS: Twenty departments submitted 1224 eligible cases of which
      909 were modified (74.3%). There was a significant increase in RV and VCC between
      the first ten patients per centre and the others. This was not seen for DC.
      Statistical analysis did not show a further significant improvement in
      delineation over the entire review period. CONCLUSION: Central review was
      feasible and increased the uniformity in CTV delineation in the first ten rectal
      cancer patients per centre. The observations in this study can be used to
      optimize future QA initiatives.

PMID- 24746580
TI  - The outcome of a multi-centre feasibility study of online adaptive radiotherapy
      for muscle-invasive bladder cancer TROG 10.01 BOLART.
AB  - PURPOSE: To assess whether online adaptive radiotherapy for bladder cancer is
      feasible across multiple Radiation Oncology departments using different imaging,
      delivery and recording technology. MATERIALS AND METHODS: A multi-centre
      feasibility study of online adaptive radiotherapy, using a choice of three "plan
      of the day", was conducted at 12 departments. Patients with muscle-invasive
      bladder cancer were included. Departments were activated if part of the pilot
      study or after a site-credentialing visit. There was real time review of the
      first two cases from each department. RESULTS: 54 patients were recruited, with
      50 proceeding to radiotherapy. There were 43 males and 7 females with a mean age
      of 78 years. The tumour stages treated included T1 (1 patient), T2 (35), T3 (10)
      and T4 (4). One patient died of an unrelated cause during radiotherapy. The three
      adaptive plans were created before the 10th fraction in all cases. In 8 (16%) of
      the patients, a conventional plan using a 'standard' CTV to PTV margin of 1.5cm
      was used for one or more fractions where the pre-treatment bladder CTV was larger
      than any of the three adaptive plans. The bladder CTV extended beyond the PTV on
      post treatment imaging in 9 (18%) of the 49 patients. CONCLUSIONS: From a
      technical perspective an online adaptive radiotherapy technique can be instituted
      in a multi-centre setting. However, without further bladder filling control or
      imaging, a CTV to PTV margin of 7mm is insufficient.

PMID- 24746581
TI  - Effect of age on response to palliative radiotherapy and quality of life in
      patients with painful bone metastases.
AB  - BACKGROUND: Multimorbidity and declining performance in elderly cancer patients
      may result in less treatment benefit. We investigated whether age is a predictor
      for pain response and quality of life (QoL) after radiotherapy in patients with
      painful bone metastases. METHODS: The database of the Dutch Bone Metastasis Study
      was used (1996-1999). 1157 patients, irradiated for painful bone metastases,
      rated their pain, QoL-domains and overall health at baseline and during follow
      up. Response was calculated taking into account changes in pain score and
      medication. Patients were grouped into three age cohorts: A: <65 (n=520), B: 65
      74 (n=410) and C: ?75years (n=227). RESULTS: No significant difference existed in
      pain response between cohorts: 78% in cohort A, 74% in B and 67% in C. When
      assessing baseline QoL, a significant difference in activity level was noticed,
      with more impairment in elderly compared to younger patients (C versus B
      (p=0.01), C versus A (p<0.001)). Other QoL-domains were similar at baseline and
      during follow-up among cohorts. A pain response was significantly associated with
      improvement of health-related QoL (OR 3.74, 95% CI 2.66-5.25). CONCLUSION: The
      majority of elderly patients with painful bone metastases responded to
      radiotherapy and showed comparable overall QoL compared to their younger
      counterparts. Age is not a predictor for pain response or QoL.

PMID- 24746582
TI  - Beam path toxicity in candidate organs-at-risk: assessment of radiation
      emetogenesis for patients receiving head and neck intensity modulated
      radiotherapy.
AB  - BACKGROUND: To investigate potential dose-response relationship between radiation
      associated nausea and vomiting (RANV) reported during radiotherapy and candidate
      nausea/vomiting-associated regions of interest (CNV-ROIs) in head and neck (HNC)
      squamous cell carcinomas. METHODS AND MATERIAL: A total of 130 patients treated
      with IMRT with squamous cell carcinomas of head and neck were evaluated. For each
      patient, CNV-ROIs were segmented manually on planning CT images. Clinical on
      treatment RANV data were reconstructed by a review of the records for all
      patients. Dosimetric data parameters were recorded from dose-volume histograms.
      Nausea and vomiting reports were concatenated as a single binary "Any N/V"
      variable, and as a "CTC-V2+" variable. RESULTS: The mean dose to CNV-ROIs was
      higher for patients experiencing RANV events. For patients receiving IMRT alone,
      a dose-response effect was observed with varying degrees of magnitude, at a
      statistically significant level for the area postrema, brainstem, dorsal vagal
      complex, medulla oblongata, solitary nucleus, oropharyngeal mucosa and whole
      brain CNV-ROIs. CONCLUSION: RANV is a common therapy-related morbidity facing
      patients receiving HNC radiotherapy, and, for those receiving radiotherapy-alone,
      is associated with modifiable dose to specific CNS structures.

PMID- 24746583
TI  - Longitudinal temporal and probabilistic prediction of survival in a cohort of
      patients with advanced cancer.
AB  - CONTEXT: Survival prognostication is important during the end of life. The
      accuracy of clinician prediction of survival (CPS) over time has not been well
      characterized. OBJECTIVES: The aims of the study were to examine changes in
      prognostication accuracy during the last 14 days of life in a cohort of patients
      with advanced cancer admitted to two acute palliative care units and to compare
      the accuracy between the temporal and probabilistic approaches. METHODS:
      Physicians and nurses prognosticated survival daily for cancer patients in two
      hospitals until death/discharge using two prognostic approaches: temporal and
      probabilistic. We assessed accuracy for each method daily during the last 14 days
      of life comparing accuracy at Day -14 (baseline) with accuracy at each time point
      using a test of proportions. RESULTS: A total of 6718 temporal and 6621
      probabilistic estimations were provided by physicians and nurses for 311
      patients, respectively. Median (interquartile range) survival was 8 days (4-20
      days). Temporal CPS had low accuracy (10%-40%) and did not change over time. In
      contrast, probabilistic CPS was significantly more accurate (P < .05 at each time
      point) but decreased close to death. CONCLUSION: Probabilistic CPS was
      consistently more accurate than temporal CPS over the last 14 days of life;
      however, its accuracy decreased as patients approached death. Our findings
      suggest that better tools to predict impending death are necessary.

PMID- 24746584
TI  - Acetic acid iontophoresis for recalcitrant scarring in post-operative.

PMID- 24746585
TI  - Compliance with guidelines for the perioperative management of vitamin K
      antagonists.
AB  - INTRODUCTION: Perioperative vitamin K antagonist management is an issue of
      concern in many countries. The availability of best practice guidelines meets
      health professionals' needs, but compliance is uncertain and should be assessed.
      MATERIALS AND METHODS: Our aim was to assess practitioner compliance with the
      guidelines on perioperative VKA management issued by the French National
      Authority for Health through a national register set up in partnership with the
      French College of Anaesthetists and Intensivists. Seven sections of data entry
      were focused on perioperative management of VKAs for elective or emergency
      procedures. High-risk patients were identified. Compliance with guidelines was
      calculated per item RESULTS: 932 charts were completed between October 2009 and
      December 2010. VKA therapy was interrupted in 74% (622/837) of elective
      procedures and bridged in 69% cases (428/622) mainly with LMWH. According to
      guidelines, bridging was strongly recommended in 39% high-risk patients (175/394)
      but 13% of these (23/175) received no bridging. Bridging was overused in 60% of
      low risk patients (242/406). Other compliance rates were as follows: (i)
      administration of therapeutic enoxaparin doses (=200IU/kg/day): only 18% of high
      risk patients (18/98), (ii) INR measurement on evening prior to the procedure 65%
      (525/803), (iii) concomitant prothrombin complex concentrate and vitamin K
      administration in emergency surgery 24% (21/87), (iv) postoperative therapeutic
      enoxaparin doses: only 20% despite widespread prescription. The incidence rate of
      bleeding and thrombotic events was 7.1% and 0.96% respectively. CONCLUSIONS:
      These poor compliance rates with guidelines suggest that the knowledge-to-action
      transfer plan was inadequate and that further interventions are required.

PMID- 24746586
TI  - [Two- and three-dimensional power Doppler ultrasound in the follow-up of placenta
      accreta treated conservatively].
AB  - OBJECTIVES: To determinate the potential of 2D and 3D-ultrasound in the follow-up
      of patients with placenta accreta treated conservatively. PATIENTS AND METHODS:
      Seven patients with placenta accreta treated conservatively during June 2007 and
      September 2009 were included. The follow-up consisted in clinical examination and
      2D/3D-ultrasound once a month. Criteria studied included clinical outcome,
      echogenicity at 2D-ultrasound, vascularisation at colour Doppler, Mean Grey at 3D
      ultrasound and vascularisation, flow and perfusion index. RESULTS: Seven women
      with invasive placenta (3 placentas accreta and 2 percreta) were studied. The
      mean follow-up was 228 days [75-369]. Mean delay for complete elimination of
      residual placenta was 280 days [120-365]. The two main results were: presence of
      an increased anechogenicpart in residual placenta before complete resorption for
      all patients; a systematic and concomitant stop of genital haemorrhage and
      vascularisation at colour Doppler. High degrees of variability in parameters
      measured at 3D-ultrasound were observed between patients so that correlations
      with clinical outcome were found. CONCLUSION: Long and regular follow-up is
      essential after conservative management but the role of 3D-ultrasound compared to
      2D-ultrasound was not demonstrated in this study.

PMID- 24746587
TI  - Small RNA cloning and sequencing strategy affects host and viral microRNA
      expression signatures.
AB  - The establishment of the microRNA (miRNA) expression signatures is the basic
      element to investigate the role played by these regulatory molecules in the
      biology of an organism. Marek's disease virus 1 (MDV-1) is an avian herpesvirus
      that naturally infects chicken and induces T cells lymphomas. During latency, MDV
      1, like other herpesviruses, expresses a limited subset of transcripts. These
      include three miRNA clusters. Several studies identified the expression of virus
      and host encoded miRNAs from MDV-1 infected cell cultures and chickens. But a
      high discrepancy was observed when miRNA cloning frequencies obtained from
      different cloning and sequencing protocols were compared. Thus, we analyzed the
      effect of small RNA library preparation and sequencing on the miRNA frequencies
      obtained from the same RNA samples collected during MDV-1 infection of chicken at
      different steps of the oncoviral pathogenesis. Qualitative and quantitative
      variations were found in the data, depending on the strategy used. One of the
      mature miRNA derived from the latency-associated-transcript (LAT), mdv1-miR-M7
      5p, showed the highest variation. Its cloning frequency was 50% of the viral
      miRNA counts when a small scale sequencing approach was used. Its frequency was
      100 times less abundant when determined through the deep sequencing approach.
      Northern blot analysis showed a better correlation with the miRNA frequencies
      found by the small scale sequencing approach. By analyzing the cellular miRNA
      repertoire, we also found a gap between the two sequencing approaches.
      Collectively, our study indicates that next-generation sequencing data considered
      alone are limited for assessing the absolute copy number of transcripts. Thus,
      the quantification of small RNA should be addressed by compiling data obtained by
      using different techniques such as microarrays, qRT-PCR and NB analysis in
      support of high throughput sequencing data. These observations should be
      considered when miRNA variations are studied prior addressing functional studies.

PMID- 24746588
TI  - In vitro characterization of an enzymatic redox cascade composed of an alcohol
      dehydrogenase, an enoate reductases and a Baeyer-Villiger monooxygenase.
AB  - An artificial enzyme cascade composed of an alcohol dehydrogenase, an enoate
      reductase and a Baeyer-Villiger monooxygenase was investigated in vitro to gain
      deeper mechanistic insights and understand the assets and drawbacks of this multi
      step biocatalysis. Several substrates composed of different structural motifs
      were examined and provided access to functionalized chiral compounds in high
      yields (up to >99%) and optical purities (up to >99%). Hence, the applicability
      of the presented enzymatic cascade was exploited for the synthesis of
      biorenewable polyesters. 

PMID- 24746589
TI  - Commentary: The incidence of nonmelanoma skin cancer: can we make an impact?

PMID- 24746590
TI  - Frailty in older persons: multisystem risk factors and the Frailty Risk Index
      (FRI).
AB  - IMPORTANCE: Currently there is no risk factor scale that identifies older persons
      at risk of frailty. OBJECTIVES: In this study, we identified significant
      multisystem risk factors of frailty, developed a simple frailty risk index, and
      evaluated it for use in primary care on an external validation cohort of
      community-living older persons. DESIGN, SETTING, AND PARTICIPANTS: We used cross
      sectional data of 1685 older adults aged 55 and older in the Singapore
      Longitudinal Ageing Studies (SLAS) to identify 13 salient risk factors among 40
      known and putative risk factors of the frailty phenotype (weakness, slowness, low
      physical activity, weight loss, and exhaustion). In a validation cohort (n =
      2478) followed for 2 years, we evaluated the validity of Frailty Risk Index
      (FRI). MAIN OUTCOMES AND MEASURES: Frailty at baseline and functional dependency,
      hospitalization, and SF12 physical component summary (PCS) scores at 2-year
      follow-up were measured among people in the validation cohort. RESULTS: The
      components (weighted scores) of the FRI are age older than 75 (2), no education
      (1), heart failure (1), respiratory disorders (2), stroke (2), depressive
      symptoms (3), hearing impairment (3), visual impairment (1), FEV1/FVC lower than
      0.7 (1), eGFR lower than 60 mL/min/1.73 m(2) (1), nutritional risk score of 3 or
      higher (2), anemia (1), and white cell counts (* 10(9)/L) of 6.5 or more (1). In
      the validation cohort, the FRI (0 to 12) was significantly associated with
      prefrailty (OR, 1.20 per unit; 95% CI 1.19-1.27) and frailty (OR 1.80 per unit;
      95% CI 1.65-1.95). The FRI predicted subsequent IADL-ADL dependency (OR1.19; 95%
      CI 1.11-1.27), hospitalization (OR .14; 95% CI 1.05-1.24), lowest quintile of
      SF12-PCS (OR 1.17; 95% CI 1.11-1.25), and combined adverse health outcomes (OR
      1.16; 95% CI 1.09-1.22). CONCLUSIONS AND RELEVANCE: The FRI is a validated
      instrument for assessing frailty risk in community-living older persons. FRI may
      be a useful rapid assessment tool to identify vital body system deficits
      underlying the frailty syndrome.

PMID- 24746591
TI  - Resident progenitors, not exogenous migratory cells, generate the majority of
      visceral mesothelium in organogenesis.
AB  - Historically, analyses of mesothelial differentiation have focused on the heart
      where a highly migratory population of progenitors originating from a localized
      "extrinsic" source moves to and over the developing organ. This model long stood
      alone as the paradigm for generation of this cell type. Here, using chick/quail
      chimeric grafting and subsequent identification of mesothelial cell populations,
      we demonstrate that a different mechanism for the generation of mesothelia exists
      in vertebrate organogenesis. In this newly discovered model, mesothelial
      progenitors are intrinsic to organs of the developing digestive and respiratory
      systems. Additionally, we demonstrate that the early heart stands alone in its
      ability to recruit an entirely exogenous mesothelial cell layer during
      development. Thus, the newly identified "organ intrinsic" model of
      mesotheliogenesis appears to predominate while the long-studied cardiac model of
      mesothelial development may be the outlier. 

PMID- 24746592
TI  - Copper and public health: dietary intakes vs. clinical data.

PMID- 24746593
TI  - Cardiopulmonary bypass in infants.

PMID- 24746594
TI  - Novel, multimodal approach for basic transesophageal echocardiographic teaching.
AB  - OBJECTIVES: Web and simulation technology may help in creating a transesophageal
      echocardiography (TEE) curriculum. The authors discuss the educational principles
      applied to developing and implementing a multimodal TEE curriculum. DESIGN AND
      SETTING: The authors modified a pilot course based on principles for effective
      simulation-based education. Key curricular elements were consistent with
      principles for effective simulation-based education: (1) clear goals and
      carefully structured objectives, (2) conveniently accessed, graduated,
      longitudinal instruction, (3) a protected and optimal learning environment, (4)
      repetition of concepts and technical skills, (5) progressive expectations for
      understanding and skill development, (6) introduction of abnormalities after
      understanding of normal anatomy and probe manipulation is achieved, (7) live
      learning sessions that are customizable to meet learner needs and individualized
      proctoring in skill sessions, (8) use of multiple approaches to teaching, (9)
      regular and relevant feedback, and (10) application of performance and compliance
      measures. PARTICIPANTS: Fifty-five learners participated in a curriculum with web
      based modules, live teaching, and simulation practice between August 2011 and May
      2013. CONCLUSION: It is possible to develop and implement an integrated,
      multimodal TEE curriculum supported by educational theory. The authors will
      explore the transferability of this approach to intraoperative TEE on live
      patients.

PMID- 24746595
TI  - Extubation in the operating room after cardiac surgery in children: a prospective
      observational study with multidisciplinary coordinated approach.
AB  - OBJECTIVE: This prospective observational study was undertaken to determine the
      feasibility of extubation of children in the operating room after cardiac
      surgery. DESIGN: A prospective observational study compared with historic
      controls. SETTING: A single tertiary care referral hospital. PARTICIPANTS: One
      thousand consecutive pediatric patients requiring cardiac surgery aged 1 day to
      18 years. Patients with spinal deformity, neurologic problems, coagulopathy as
      diagnosed by high international normalized ratio (INR) more than 1.5, and
      patients preoperatively on mechanical ventilation were excluded from the study.
      Data were also reviewed for another 1,000 patients operated before the beginning
      of this study, which constituted historic controls. INTERVENTIONS: All 1,000
      patients were considered as potential candidates for extubation in the operating
      room after cardiac surgery and managed by a combination of general anesthesia and
      neuraxial analgesia with a mixture of caudal morphine and dexmedetomidine, and
      extubation in the operating room was attempted after completion of the surgical
      procedure. These comprised the study group (SG). Data also were reviewed for
      another 1,000 patients before the beginning of this study when extubation in the
      operating room was not attempted and compared with this group to study the impact
      of extubation in the operating room on intensive care unit (ICU) stay and
      resource utilization. This data comprised the before-study group (BSG).
      MEASUREMENTS AND MAIN RESULTS: Eight hundred seventy-one (87.1%) patients were
      extubated in the operating room. This included 40% of neonates and 70%, 85%, and
      91% of patients aged between 1 and 3 months, 3 months to 1 year, and more than 1
      year, respectively. Forty-five patients (4.5%) required re-intubation within 24
      hours, and 9 patients died among those extubated in the OR, but for reasons
      thought not to be related to extubation. The ICU stay was significantly less in
      the study group (2.56+/-1.84 v 5.4+/-2.32 days, p<0.0001) as compared to before
      study group (BSG). The number of patients in the ICU (34.76+/-3.19 v 59.98+/
      4.92, p<0.0001) and the number of patients on a ventilator (5.1+/-1.24 v 24.5+/
      2.88, p<0.0001) on a daily basis were significantly less in the study group,
      reflecting positive impact on resource utilization. CONCLUSION: Extubation in the
      operating room was successful in 87.1% of the patients without any increase in
      mortality and morbidity, but with a decrease in ICU length of stay and less use
      of hospital resources.

PMID- 24746596
TI  - Three-dimensional echocardiography: raising questions and providing answers.

PMID- 24746597
TI  - Intrathecal lactate as a predictor of early- but not late-onset spinal cord
      injury in thoracoabdominal aneurysmectomy.
AB  - OBJECTIVE: To evaluate the role of intrathecal lactate as an early predictor of
      spinal cord injury during thoracoabdominal aortic aneurysmectomy. DESIGN:
      Observational study. SETTING: University hospital. PARTICIPANTS: Forty-four
      consecutive patients scheduled to undergo thoracoabdominal aortic aneurysmectomy.
      Two patients had a type-B dissecting aneurysm while the other 42 patients
      suffered from degenerative aneurysm. INTERVENTIONS: None. METHODS: During
      surgery, samples of cerebrospinal fluid and arterial blood were withdrawn
      simultaneously to evaluate lactate concentration. Samples were collected at 4
      fixed times during and after surgery: T1 (beginning of the intervention), T2 (15
      minutes after aortic cross-clamping), T3 (just before unclamping), T4 (end of
      surgery). MEASUREMENTS AND MAIN RESULTS: Mean lactate levels in cerebrospinal
      fluid rose consistently and steadily from the beginning of the intervention until
      after surgery (T1 = 1.83 mmol/L), T2 = 2.10 mmol/L, T3 = 2.72 mmol/L, T4 = 3.70
      mmol/L). Seven patients developed spinal cord injury; two of them had delayed
      injury occurring 24 hours after the end of surgery; the remaining 5 had early
      onset. In this group of 5 patients, preoperative cerebrospinal fluid lactate
      levels were significantly (p = 0.04) higher than those of the other 37 patients
      preoperatively (2.12 +/- 0.35 v 1.79 +/- 0.29 mmol/L). CONCLUSIONS: Preoperative
      cerebrospinal lactate concentration is elevated in patients who will develop
      early-onset spinal cord injury after thoracoabdominal aortic aneurysmectomy. This
      may allow a better stratification of these patients, suggesting a more aggressive
      strategy of spinal cord function preservation, such as systematic reimplanting of
      intercostal arteries, and possibly obtaining a better outcome.

PMID- 24746598
TI  - Operator learning curve for transradial percutaneous coronary interventions:
      implications for the initiation of a transradial access program in contemporary
      US practice.
AB  - OBJECTIVES: Our study aimed to assess the characteristics and outcomes of
      transfemoral approach (TFA) versus the initial steps of a transradial approach
      (TRA) program and to assess the learning curve of TRA in contemporary, US
      practice. BACKGROUND: When compared to TFA, TRA has been shown to lower bleeding
      and vascular complications during percutaneous coronary intervention (PCI).
      However, use of TRA is still low. There are limited data regarding the
      characteristics of TRA learning curve, especially in an era with designated TRA
      equipment. METHODS: Consecutive patients undergoing PCI in a single US center
      were divided into two cohorts according to vascular access approach: the last 250
      TFA patients prior to the establishment of a TRA program and the initial 239 TRA
      patients following the establishment of a TRA program. Subgroup analysis of the
      TRA group, which was divided into five sequential case groups of 50 cases per
      group, was performed in order to assess TRA learning curve. RESULTS: Overall, the
      baseline characteristics of TFA vs. TRA groups were comparable. Fluoroscopy time
      was significantly longer during TRA procedures (18+/-11 vs. 15+/-8min,
      respectively, p=0.002); however, contrast use was lower during TRA procedures
      (161+/-72 vs. 180+/-63ml, respectively, p=0.002). In-hospital outcomes were
      similar between the two groups, with low frequencies of mortality, myocardial
      infarction, and stent thrombosis. Subanalysis of TRA group for learning curve
      assessment showed no major differences in patient demographics among the five
      subgroups. In the initial cases, more PCI was performed among non-acute cases
      (62% in patients 1-50 vs. 8-27% in patients 51-239, p<0.001). Despite these
      differences, characteristics of the treated vessels were similar between groups.
      There was no significant change in fluoroscopy time or in the amount of iodinated
      contrast volume delivered. Similarly, no differences in procedural, in-hospital,
      and long-term outcomes were documented. CONCLUSIONS: Adopting TRA as a default is
      feasible for high-volume operators without significant learning curve effects.

PMID- 24746599
TI  - Randomized comparison of operator radiation exposure comparing transradial and
      transfemoral approach for percutaneous coronary procedures: rationale and design
      of the minimizing adverse haemorrhagic events by TRansradial access site and
      systemic implementation of angioX - RAdiation Dose study (RAD-MATRIX).
AB  - BACKGROUND: Radiation absorbed by interventional cardiologists is a frequently
      under-evaluated important issue. Aim is to compare radiation dose absorbed by
      interventional cardiologists during percutaneous coronary procedures for acute
      coronary syndromes comparing transradial and transfemoral access. METHODS: The
      randomized multicentre MATRIX (Minimizing Adverse Haemorrhagic Events by
      TRansradial Access Site and Systemic Implementation of angioX) trial has been
      designed to compare the clinical outcome of patients with acute coronary
      syndromes treated invasively according to the access site (transfemoral vs.
      transradial) and to the anticoagulant therapy (bivalirudin vs. heparin). Selected
      experienced interventional cardiologists involved in this study have been
      equipped with dedicated thermoluminescent dosimeters to evaluate the radiation
      dose absorbed during transfemoral or right transradial or left transradial
      access. For each access we evaluate the radiation dose absorbed at wrist, at
      thorax and at eye level. Consequently the operator is equipped with three sets
      (transfemoral, right transradial or left transradial access) of three different
      dosimeters (wrist, thorax and eye dosimeter). Primary end-point of the study is
      the procedural radiation dose absorbed by operators at thorax. An important
      secondary end-point is the procedural radiation dose absorbed by operators
      comparing the right or left radial approach. Patient randomization is performed
      according to the MATRIX protocol for the femoral or radial approach. A further
      randomization for the radial approach is performed to compare right and left
      transradial access. CONCLUSIONS: The RAD-MATRIX study will probably consent to
      clarify the radiation issue for interventional cardiologist comparing transradial
      and transfemoral access in the setting of acute coronary syndromes.

PMID- 24746600
TI  - Orbital atherectomy system in treating calcified coronary lesions: 3-Year follow
      up in first human use study (ORBIT I trial).
AB  - BACKGROUND/PURPOSE: The ORBIT I trial evaluated the safety and performance of an
      orbital atherectomy system (OAS) in treating de novo calcified coronary lesions.
      Severely calcified coronary arteries pose ongoing treatment challenges. Stent
      placement in calcified lesions can result in stent under expansion, malapposition
      and procedural complications. OAS treatment may be recommended to facilitate
      coronary stent implantation in these difficult lesions. MATERIALS/METHODS: Fifty
      patients with de novo calcified coronary lesions were enrolled in the ORBIT I
      trial. Patients were treated with the OAS followed by stent placement. Our
      institution treated 33/50 patients and continued follow-up for 3 years. RESULTS:
      Average age was 54.4 years and 90.9% were males. Mean lesion length was 15.9mm.
      The average number of OAS devices used per patient was 1.3. Procedural success
      was achieved in 97% of patients. Angiographic complications were observed in five
      patients (two minor dissections, one major dissection and two perforations). The
      cumulative major adverse cardiac event (MACE) rate was 6.1% in-hospital, 9.1% at
      30 days, 12.1% at 6 months, 15.2% at 2 years, and 18.2% at 3years. The MACE rate
      included two in-hospital non Q-wave myocardial infarctions (MI), one additional
      non Q-wave MI at 30 days leading to target lesion revascularization (TLR), and
      three cardiac deaths. CONCLUSIONS: The ORBIT I trial suggests that OAS treatment
      may offer an effective method to modify calcified coronary lesion compliance to
      facilitate optimal stent placement in these difficult-to-treat patients with
      acceptable levels of safety up to 3 years post-index procedure.

PMID- 24746601
TI  - De novo transcriptome analysis of the Siberian apricot (Prunus sibirica L.) and
      search for potential SSR markers by 454 pyrosequencing.
AB  - The Siberian apricot, an economically and ecologically important plant in China,
      contains seeds high in oil and can grow on marginal land. Although this species
      has multiple purposes and may be a feedstock of biofuel in China, transcriptome
      information and molecular research on this species remain limited. RNA-Seq
      technology has been widely applied to transcriptomics, genomics and the
      development of molecular markers, and functional gene studies. In this study, we
      obtained 1,243,067 high-quality reads with a mean size of 425 bp in a single run,
      totaling 528.4 Mb of sequence data using 454 GS FLX Titanium sequencing. All
      reads were assembled de novo into 46,940 unigenes with a mean size of 651 bp
      (range: 45-5566 bp). Assembled unigenes were annotated in multiple public
      databases based on similarity alignments to genes and proteins. 191 unigenes
      involving in lipid biosynthesis and metabolism were found, among them, expression
      patterns of two desaturase enzymes were analyzed by quantitative real-time
      polymerase chain reaction (qRT-PCR), based on six tissues from Siberian apricot,
      the seeds had the highest expression. 7304 simple sequence repeats (SSR) were
      identified from 6509 unigenes, a total of 9930 primer pairs were designed, 50
      primer pairs were randomly selected to validate of the usefulness, and 24 (48%)
      primer pairs produced bands of the expected size. These data provide a base of
      sequence information to improve agronomic characters and molecular marker
      assisted breeding to alter the composition of fatty acids in seeds from this
      plant, and hence, facilitate its utilization as a future biodiesel feedstock.

PMID- 24746602
TI  - Honey, Hadza, hunter-gatherers, and human evolution.
AB  - Honey is the most energy dense food in nature. It is therefore not surprising
      that, where it exists, honey is an important food for almost all hunter
      gatherers. Here we describe and analyze widespread honey collecting among
      foragers and show that where it is absent, in arctic and subarctic habitats,
      honey bees are also rare to absent. Second, we focus on one hunter-gatherer
      society, the Hadza of Tanzania. Hadza men and women both rank honey as their
      favorite food. Hadza acquire seven types of honey. Hadza women usually acquire
      honey that is close to the ground while men often climb tall baobab trees to raid
      the largest bee hives with stinging bees. Honey accounts for a substantial
      proportion of the kilocalories in the Hadza diet, especially that of Hadza men.
      Cross-cultural forager data reveal that in most hunter-gatherers, men acquire
      more honey than women but often, as with the Hadza, women do acquire some.
      Virtually all warm-climate foragers consume honey. Our closest living relatives,
      the great apes, take honey when they can. We suggest that honey has been part of
      the diet of our ancestors dating back to at least the earliest hominins. The
      earliest hominins, however, would have surely been less capable of acquiring as
      much honey as more recent, fully modern human hunter-gatherers. We discuss
      reasons for thinking our early ancestors would have acquired less honey than
      foragers ethnographically described, yet still significantly more than our great
      ape relatives.

PMID- 24746603
TI  - Effects of aging on whole body and segmental control while obstacle crossing
      under impaired sensory conditions.
AB  - The ability to safely negotiate obstacles is an important component of
      independent mobility, requiring adaptive locomotor responses to maintain dynamic
      balance. This study examined the effects of aging and visual-vestibular
      interactions on whole-body and segmental control during obstacle crossing. Twelve
      young and 15 older adults walked along a straight pathway and stepped over one
      obstacle placed in their path. The task was completed under 4 conditions which
      included intact or blurred vision, and intact or perturbed vestibular information
      using galvanic vestibular stimulation (GVS). Global task performance
      significantly increased under suboptimal vision conditions. Vision also
      significantly influenced medial-lateral center of mass displacement, irrespective
      of age and GVS. Older adults demonstrated significantly greater trunk pitch and
      head roll angles under suboptimal vision conditions. Similar to whole-body
      control, no GVS effect was found for any measures of segmental control. The
      results indicate a significant reliance on visual but not vestibular information
      for locomotor control during obstacle crossing. The lack of differences in GVS
      effects suggests that vestibular information is not up-regulated for obstacle
      avoidance. This is not differentially affected by aging. In older adults,
      insufficient visual input appears to affect ability to minimize anterior
      posterior trunk movement despite a slower obstacle crossing time and walking
      speed. Combined with larger medial-lateral deviation of the body COM with
      insufficient visual information, the older adults may be at a greater risk for
      imbalance or inability to recover from a possible trip when stepping over an
      obstacle. 

PMID- 24746604
TI  - Augmented multisensory feedback enhances locomotor adaptation in humans with
      incomplete spinal cord injury.
AB  - Different forms of augmented feedback may engage different motor learning
      pathways, but it is unclear how these pathways interact with each other,
      especially in patients with incomplete spinal cord injury (SCI). The purpose of
      this study was to test whether augmented multisensory feedback could enhance
      aftereffects following short term locomotor training (i.e., adaptation) in
      patients with incomplete SCI. A total of 10 subjects with incomplete SCI were
      recruited to perform locomotor adaptation. Three types of augmented feedback were
      provided during the adaptation: (a) computerized visual cues showing the actual
      and target stride length (augmented visual feedback); (b) a swing resistance
      applied to the leg (augmented proprioceptive feedback); (c) a combination of the
      visual cues and resistance (augmented multisensory feedback). The results showed
      that subjects' stride length increased in all conditions following the
      adaptation, but the increase was greater and retained longer in the multisensory
      feedback condition. The multisensory feedback provided in this study may engage
      both explicit and implicit learning pathways during the adaptation and in turn
      enhance the aftereffect. The results implied that multisensory feedback may be
      used as an adjunctive approach to enhance gait recovery in humans with SCI. 

PMID- 24746605
TI  - Ankle plantarflexion strength in rearfoot and forefoot runners: a novel
      clusteranalytic approach.
AB  - The purpose of the present study was to test for differences in ankle
      plantarflexion strengths of habitually rearfoot and forefoot runners. In order to
      approach this issue, we revisit the problem of classifying different footfall
      patterns in human runners. A dataset of 119 subjects running shod and barefoot
      (speed 3.5m/s) was analyzed. The footfall patterns were clustered by a novel
      statistical approach, which is motivated by advances in the statistical
      literature on functional data analysis. We explain the novel statistical approach
      in detail and compare it to the classically used strike index of Cavanagh and
      Lafortune (1980). The two groups found by the new cluster approach are well
      interpretable as a forefoot and a rearfoot footfall groups. The subsequent
      comparison study of the clustered subjects reveals that runners with a forefoot
      footfall pattern are capable of producing significantly higher joint moments in a
      maximum voluntary contraction (MVC) of their ankle plantarflexor muscles tendon
      units; difference in means: 0.28Nm/kg. This effect remains significant after
      controlling for an additional gender effect and for differences in training
      levels. Our analysis confirms the hypothesis that forefoot runners have a higher
      mean MVC plantarflexion strength than rearfoot runners. Furthermore, we
      demonstrate that our proposed stochastic cluster analysis provides a robust and
      useful framework for clustering foot strikes. 

PMID- 24746606
TI  - Supervised methods for detection and segmentation of tissues in clinical lumbar
      MRI.
AB  - Lower back pain (LBP) is widely prevalent all over the world and more than 80% of
      the people suffer from LBP at some point of their lives. Moreover, a shortage of
      radiologists is the most pressing cause for the need of CAD (computer-aided
      diagnosis) systems. Automatic localization and labeling of intervertebral discs
      from lumbar MRI is the first step towards computer-aided diagnosis of lower back
      ailments. Subsequently, for diagnosis and characterization (quantification and
      localization) of abnormalities like disc herniation and stenosis, a completely
      automatic segmentation of intervertebral discs and the dural sac is extremely
      important. Contribution of this paper towards clinical CAD systems is two-fold.
      First, we propose a method to automatically detect all visible intervertebral
      discs in clinical sagittal MRI using heuristics and machine learning techniques.
      We provide a novel end-to-end framework that outputs a tight bounding box for
      each disc, instead of simply marking the centroid of discs, as has been the trend
      in the recent past. Second, we propose a method to simultaneously segment all the
      tissues (vertebrae, intervertebral disc, dural sac and background) in a lumbar
      sagittal MRI, using an auto-context approach instead of any explicit shape
      features or models. Past work tackles the lumbar segmentation problem on a
      tissue/organ basis, and which tend to perform poorly in clinical scans due to
      high variability in appearance. We, on the other hand, train a series of robust
      classifiers (random forests) using image features and sparsely sampled context
      features, which implicitly represent the shape and configuration of the image.
      Both these methods have been tested on a huge clinical dataset comprising of 212
      cases and show very promising results for both disc detection (98% disc
      localization accuracy and 2.08mm mean deviation) and sagittal MRI segmentation
      (dice similarity indices of 0.87 and 0.84 for the dural sac and the inter
      vertebral disc, respectively). 

PMID- 24746607
TI  - Ultrastructural immunocytochemistry suggests that periderm granules in embryonic
      chick epidermis contain beta-defensins.
AB  - The capability to express an innate antimicrobial action through the production
      of beta-defensins in the skin of chick embryos has been studied by
      immunocytochemistry. The immunolabeling of periderm granules present in the
      initial embryonic epidermis of the chick is obtained with a lizard anti-defensin
      antibody (Ac-BD-15) that recognizes a homologous peptide in the chick beta
      defensin 9. Similar granules, termed honeycomb granules, are also stored in some
      basophilic granulocytes of adult and hatchling chicks, but did not show
      immunoreactivity to the antibody. It is unclear whether this morphology indicates
      different organelles, content or lack of available antigens due to organelle
      packaging. The remarkable ultrastructural similarity between periderm granules
      and the honeycomb granules present in basophil granulocytes further indicates
      that embryonic keratinocytes can synthesize antimicrobial peptides together with
      corneous proteins. These peptides may participate in the formation of an
      epidermal microbial barrier during ontogenesis or protect the embryo in case of
      damage to the amniotic-periderm barrier. These transient organelles, apart from
      the early keratinization of the epidermis that forms the initial barrier before
      hatching may also contribute to the formation of an efficient anti-microbial
      barrier against the penetration of microbes during embryonic life until hatching
      when the adaptive immunity system is still immature. 

PMID- 24746608
TI  - Investigation of the first outbreak of OXA-48-producing Klebsiella pneumoniae in
      Ireland.
AB  - BACKGROUND: Carbapenemase-producing Enterobacteriaceae (CPE) strains are
      encountered with increasing frequency in Europe. In November 2010 the European
      Centre for Disease Control (ECDC) graded Ireland as only having sporadic
      occurrence of CPE. AIM: To describe the epidemiological and molecular typing
      analysis of the first outbreak of OXA-48-producing Klebsiella pneumoniae in an
      Irish tertiary care referral centre. METHODS: Sixteen OXA-48-producing K.
      pneumoniae isolates were detected, from both clinical and screening specimens,
      and analysed by pulsed-field gel electrophoresis and by multi-locus sequence
      typing. FINDINGS: Typing analysis revealed that two outbreak strains were
      circulating in the hospital, one among surgical patients and one among medical
      patients. The 'medical strain' ST13 had already been identified as an
      internationally disseminated clone, whereas the 'surgical strain' ST221 had not
      previously been reported as an OXA-48-carrying strain. CONCLUSION: Although the
      outbreak on surgical wards was successfully controlled by implementing strict
      infection control measures, intermittent detection of individual patients
      carrying the 'medical strain' of OXA-48 K. pneumoniae has persisted since then.
      The experience from this outbreak suggests that OXA-48 K. pneumoniae is endemic
      at low level in the healthcare setting in the Dublin region.

PMID- 24746609
TI  - A 10-year survey of fungal aerocontamination in hospital corridors: a reliable
      sentinel to predict fungal exposure risk?
AB  - BACKGROUND: Invasive mould infections represent a threat for high-risk patients
      hospitalized in haematology units. French guidelines recommend that fungal
      aerocontamination monitoring should be performed quarterly. Since 2002, Besancon
      University Hospital has expanded to include several new buildings. Consequently,
      environmental surveys have been re-inforced and are now performed on a weekly
      basis. AIM: To retrospectively assess the contribution of fungal
      aerocontamination measurement in haematology corridors and main hospital
      corridors as a sentinel to assess fungal exposure and risk of invasive mould
      infections. METHODS: Over a 10-year period, 2706 air samples were taken by
      impaction every week in the same locations in haematology corridors and main
      hospital corridors. All fungal species were identified. The Haematology and
      Hospital Hygiene Departments were alerted systematically whenever a peak of
      opportunistic species was detected and corrective action was planned. Since 2007,
      each case of invasive aspergillosis has been reported to the French health
      authorities. Cuzick's test, Mann-Kendall's trend test, autocorrelation and
      Spearman's correlation rank test were used for statistical analysis. FINDINGS:
      Over 10 years of surveillance, 12 peaks of Aspergillus fumigatus (>40 colony
      forming units/m(3)) were observed in the main hospital corridors, and A.
      fumigatus contamination was detected up to six times per year in the haematology
      corridors. In order to limit fungal exposure, the decision was made to perform
      additional checks on ventilation systems and heating, increase biocleaning and
      develop clear instructions. CONCLUSION: No significant link was observed between
      A. fumigatus detection and invasive aspergillosis. Weekly surveys have helped to
      improve the vigilance of the medical teams. Nevertheless, 58 cases of invasive
      aspergillosis have been identified since 2007.

PMID- 24746610
TI  - Bacterial ecology of hospital workers' facial hair: a cross-sectional study.
AB  - It is unknown whether healthcare workers' facial hair harbours nosocomial
      pathogens. We compared facial bacterial colonization rates among 408 male
      healthcare workers with and without facial hair. Workers with facial hair were
      less likely to be colonized with Staphylococcus aureus (41.2% vs 52.6%, P = 0.02)
      and meticillin-resistant coagulase-negative staphylococci (2.0% vs 7.0%, P =
      0.01). Colonization rates with Gram-negative organisms were low for all
      healthcare workers, and Gram-negative colonization rates did not differ by facial
      hair type. Overall, colonization is similar in male healthcare workers with and
      without facial hair; however, certain bacterial species were more prevalent in
      workers without facial hair.

PMID- 24746611
TI  - Kidney disease and infection.

PMID- 24746612
TI  - Calcitonin gene-related peptide (CGRP) in autonomic cardiovascular regulation and
      vascular structure.
AB  - Calcitonin gene-related peptide (CGRP) is reported to play important roles in
      cardiovascular regulation in human and animal models. In spite of this, its role
      remains controversial. We aim to clarify this by studying the autonomic
      cardiovascular function and vascular structure in CGRP knockout (CGRP(-/-)) mice.
      Blood pressure (BP) and heart rate (HR) were assessed by telemeters. Urine (24
      hour) and blood were collected for catecholamines measurements. Baroreflex
      sensitivity was assessed using phenylephrine and sodium nitroprusside
      administered in an acute study. Daytime mean arterial pressure (MAP; 12-hour
      period) was significantly higher in the CGRP(-/-) mice than in the wild type (WT)
      mice (114.5 vs. 104.5 mm Hg; P = .04). Norepinephrine was elevated in plasma and
      24-hour urine in the knockouts (Urine, 956 vs. 618 pg/mL; P = .004; Plasma, 2505
      vs. 1168 pg/mL; P = .04). Paradoxically, cardiovagal baroreflex sensitivity was
      higher in CGRP(-/-) mice (3.2 vs. 1.4 ms/mm Hg; P = .03). To increase insight, we
      studied aortic stiffness in CGRP(-/-) mice and found it increased compared with
      age-matched WT mice, as evidenced by the depression of the compliance curve (P <
      .05). CGRP(-/-) mice have higher BP due to elevated sympathetic signals and
      abnormalities in blood vessel structure. Moreover, our data also showed that CGRP
      plays an important role in the regulation of the cardio-vagal tone.

PMID- 24746613
TI  - Clinical determinants and prognostic significance of the electrocardiographic
      strain pattern in chronic kidney disease patients.
AB  - The electrocardiographic (ECG) strain pattern (Strain) is a marker of left
      ventricular hypertrophy (LVH) severity that provides additional prognostic
      information beyond echocardiography (ECHO) in the community level. We sought to
      evaluate its clinical determinants and prognostic usefulness in chronic kidney
      disease (CKD) patients. We evaluated 284 non-dialysis-dependent patients with CKD
      stages 3 to 5 (mean age, 61 years [interquartile range, 53-67 years]; 62% men).
      Patients were followed for 23 months (range, 13-32 months) for cardiovascular
      (CV) events and/or death. Strain patients (n = 37; 13%) were using more
      antihypertensive drugs, had higher prevalence of peripheral vascular disease and
      smoking, and higher levels of C-reactive protein, cardiac troponin, and brain
      natriuretic peptide (BNP). The independent predictors of Strain were: left
      ventricular mass index (LVMI), BNP, and smoking. During follow-up, there were 44
      cardiovascular events (fatal and non-fatal) and 22 non-CV deaths; and Strain was
      associated with a worse prognosis independently of LVMI. Adding Strain to a
      prognostic model of LVMI improved in 15% the risk discrimination for the
      composite endpoint and in 12% for the CV events. Strain associates with CV risk
      factors and adds prognostic information over and above that of ECHO-assessed
      LVMI. Its routine screening may allow early identification of high risk CKD
      patients. 

PMID- 24746614
TI  - Temporal activation of Nrf2 in the penumbra and Nrf2 activator-mediated
      neuroprotection in ischemia-reperfusion injury.
AB  - Oxidative stress plays a critical role in mediating tissue injury and neuron
      death during ischemia-reperfusion injury (IRI). The Keap1-Nrf2 defense pathway
      serves as a master regulator of endogenous antioxidant defense, and Nrf2 has been
      attracting attention as a target for the treatment of IRI. In this study, we
      evaluated Nrf2 expression in IRI using OKD (Keap1-dependent oxidative stress
      detector) mice and investigated the neuroprotective ability of an Nrf2 activator.
      We demonstrated temporal changes in Nrf2 expression in the same mice with
      luciferase assays and an Nrf2 activity time course using Western blotting. We
      also visualized Nrf2 expression in the ischemic penumbra and investigated Nrf2
      expression in mice and humans using immunohistochemistry. Endogenous Nrf2
      upregulation was not detected early in IRI, but expression peaked 24h after
      ischemia. Nrf2 expression was mainly detected in the penumbra, and it was found
      in neurons and astrocytes in both mice and humans. Intravenous administration of
      the Nrf2 activator bardoxolone methyl (BARD) resulted in earlier upregulation of
      Nrf2 and heme oxygenase-1. Furthermore, BARD decreased infarction volume and
      improved neurological symptoms after IRI. These findings indicate that earlier
      Nrf2 activation protects neurons, possibly via effects on astrocytes. 

PMID- 24746616
TI  - Production of superoxide/H2O2 by dihydroorotate dehydrogenase in rat skeletal
      muscle mitochondria.
AB  - Dehydrogenases that use ubiquinone as an electron acceptor, including complex I
      of the respiratory chain, complex II, and glycerol-3-phosphate dehydrogenase, are
      known to be direct generators of superoxide and/or H2O2. Dihydroorotate
      dehydrogenase oxidizes dihydroorotate to orotate and reduces ubiquinone to
      ubiquinol during pyrimidine metabolism, but it is unclear whether it produces
      superoxide and/or H2O2 directly or does so only indirectly from other sites in
      the electron transport chain. Using mitochondria isolated from rat skeletal
      muscle we establish that dihydroorotate oxidation leads to superoxide/H2O2
      production at a fairly high rate of about 300pmol H2O2.min(-1).mg protein(-1)
      when oxidation of ubiquinol is prevented and complex II is uninhibited. This H2O2
      production is abolished by brequinar or leflunomide, known inhibitors of
      dihydroorotate dehydrogenase. Eighty percent of this rate is indirect,
      originating from site IIF of complex II, because it can be prevented by malonate
      or atpenin A5, inhibitors of complex II. In the presence of inhibitors of all
      known sites of superoxide/H2O2 production (rotenone to inhibit sites in complex I
      (site IQ and, indirectly, site IF), myxothiazol to inhibit site IIIQo in complex
      III, and malonate plus atpenin A5 to inhibit site IIF in complex II),
      dihydroorotate dehydrogenase generates superoxide/H2O2, at a small but
      significant rate (23pmol H2O2.min(-1).mg protein(-1)), from the ubiquinone
      binding site. We conclude that dihydroorotate dehydrogenase can generate
      superoxide and/or H2O2 directly at low rates and is also capable of indirect
      production at higher rates from other sites through its ability to reduce the
      ubiquinone pool. 

PMID- 24746615
TI  - Methylglyoxal induces endoplasmic reticulum stress and DNA demethylation in the
      Keap1 promoter of human lens epithelial cells and age-related cataracts.
AB  - Age-related cataracts are a leading cause of blindness. Previously, we have
      demonstrated the association of the unfolded protein response with various
      cataractogenic stressors. However, DNA methylation alterations leading to
      suppression of lenticular antioxidant protection remains unclear. Here, we report
      the methylglyoxal-mediated sequential events responsible for Keap1 promoter DNA
      demethylation in human lens epithelial cells, because Keap1 is a negative
      regulatory protein that regulates the Nrf2 antioxidant protein. Methylglyoxal
      induces endoplasmic reticulum stress and activates the unfolded protein response
      leading to overproduction of reactive oxygen species before human lens epithelial
      cell death. Methylglyoxal also suppresses Nrf2 and DNA methyltransferases but
      activates the DNA demethylation pathway enzyme TET1. Bisulfite genomic DNA
      sequencing confirms the methylglyoxal-mediated Keap1 promoter DNA demethylation
      leading to overexpression of Keap1 mRNA and protein. Similarly, bisulfite genomic
      DNA sequencing shows that human clear lenses (n = 15) slowly lose 5
      methylcytosine in the Keap1 promoter throughout life, at a rate of 1% per year.
      By contrast, diabetic cataractous lenses (n = 21) lose an average of 90% of the 5
      methylcytosine regardless of age. Overexpressed Keap1 protein is responsible for
      decreasing Nrf2 by proteasomal degradation, thereby suppressing Nrf2-dependent
      stress protection. This study demonstrates for the first time the associations of
      unfolded protein response activation, Nrf2-dependent antioxidant system failure,
      and loss of Keap1 promoter methylation because of altered active and passive DNA
      demethylation pathway enzymes in human lens epithelial cells by methylglyoxal. As
      an outcome, the cellular redox balance is altered toward lens oxidation and
      cataract formation. 

PMID- 24746617
TI  - Inducible nitric oxide synthase is key to peroxynitrite-mediated, LPS-induced
      protein radical formation in murine microglial BV2 cells.
AB  - Microglia are the resident immune cells in the brain. Microglial activation is
      characteristic of several inflammatory and neurodegenerative diseases including
      Alzheimer's disease, multiple sclerosis, and Parkinson's disease. Though
      lipopolysaccharide (LPS)-induced microglial activation in models of Parkinson's
      disease is well documented, the free radical-mediated protein radical formation
      and its underlying mechanism during LPS-induced microglial activation are not
      known. Here we have used immuno-spin trapping and RNA interference to investigate
      the role of inducible nitric oxide synthase (iNOS) in peroxynitrite-mediated
      protein radical formation in murine microglial BV2 cells treated with LPS.
      Treatment of BV2 cells with LPS resulted in morphological changes, induction of
      iNOS, and increased protein radical formation. Pretreatments with FeTPPS (a
      peroxynitrite decomposition catalyst), L-NAME (total NOS inhibitor), 1400W (iNOS
      inhibitor), and apocynin significantly attenuated LPS-induced protein radical
      formation and tyrosine nitration. Results obtained with coumarin-7-boronic acid,
      a highly specific probe for peroxynitrite detection, correlated with LPS-induced
      tyrosine nitration, which demonstrated involvement of peroxynitrite in protein
      radical formation. A similar degree of protection conferred by 1400W and L-NAME
      led us to conclude that only iNOS, and no other forms of NOS, is involved in LPS
      induced peroxynitrite formation. Subsequently, siRNA for iNOS, the iNOS-specific
      inhibitor 1400W, the NF-kappaB inhibitor PDTC, and the p38 MAPK inhibitor
      SB202190 was used to inhibit iNOS directly or indirectly. Inhibition of iNOS
      precisely correlated with decreased protein radical formation in LPS-treated BV2
      cells. The time course of protein radical formation also matched the time course
      of iNOS expression. Taken together, these results prove the role of iNOS in
      peroxynitrite-mediated protein radical formation in LPS-treated microglial BV2
      cells.

PMID- 24746618
TI  - (-)-Epicatechin mitigates high-fructose-associated insulin resistance by
      modulating redox signaling and endoplasmic reticulum stress.
AB  - We investigated the capacity of dietary (-)-epicatechin (EC) to mitigate insulin
      resistance through the modulation of redox-regulated mechanisms in a rat model of
      metabolic syndrome. Adolescent rats were fed a regular chow diet without or with
      high fructose (HFr; 10% w/v) in drinking water for 8 weeks, and a group of HFr
      fed rats was supplemented with EC in the diet. HFr-fed rats developed insulin
      resistance, which was mitigated by EC supplementation. Accordingly, the
      activation of components of the insulin signaling cascade (insulin receptor,
      IRS1, Akt, and ERK1/2) was impaired, whereas negative regulators (PKC, IKK, JNK,
      and PTP1B) were upregulated in the liver and adipose tissue of HFr rats. These
      alterations were partially or totally prevented by EC supplementation. In
      addition, EC inhibited events that contribute to insulin resistance: HFr
      associated increased expression and activity of NADPH oxidase, activation of
      redox-sensitive signals, expression of NF-kappaB-regulated proinflammatory
      cytokines and chemokines, and some sub-arms of endoplasmic reticulum stress
      signaling. Collectively, these findings indicate that EC supplementation can
      mitigate HFr-induced insulin resistance and are relevant for defining
      interventions that can prevent/mitigate MetS-associated insulin resistance. 

PMID- 24746619
TI  - Hsp27 suppresses the Cu(2+)-induced amyloidogenicity, redox activity, and
      cytotoxicity of alpha-synuclein by metal ion stripping.
AB  - Aberrant copper homeostasis and oxidative stress have critical roles in several
      neurodegenerative diseases. Expression of heat-shock protein 27 (Hsp27) is
      elevated under oxidative stress as well as upon treatment with Cu(2+), and
      elevated levels of Hsp27 are found in the brains of patients with Alzheimer and
      Parkinson diseases. We demonstrate, using steady-state and time-resolved
      fluorescence spectroscopy as well as isothermal titration calorimetry studies,
      that Hsp27 binds Cu(2+) with high affinity (Kd ~10(-11) M). Treating IMR-32 human
      neuroblastoma cells with Cu(2+) leads to upregulation of endogenous Hsp27.
      Further, overexpression of Hsp27 in IMR-32 human neuroblastoma cells confers
      cytoprotection against Cu(2+)-induced cell death. Hsp27 prevents the deleterious
      interaction of Cu(2+) with alpha-synuclein, the protein involved in Parkinson
      disease and synucleinopathies. Hsp27 attenuates Cu(2+)- or Cu(2+)-alpha-synuclein
      mediated generation of reactive oxygen species and confers cytoprotection on IMR
      32 cells as well as on mouse primary neural precursor cells. Hsp27 prevents
      Cu(2+)-ascorbate or Cu(2+)-alpha-synuclein-ascorbate treatment-induced increase
      in mitochondrial superoxide level and mitochondrial disorganization in IMR-32
      cells. Hsp27 dislodges the alpha-synuclein-bound Cu(2+) and prevents the Cu(2+)
      mediated amyloidogenesis of alpha-synuclein. Our findings that Hsp27 binds Cu(2+)
      with high affinity leading to beneficial effects and that Hsp27 can dislodge
      Cu(2+) from alpha-synuclein, preventing amyloid fibril formation, indicate
      potential therapeutic strategies for neurodegenerative diseases involving
      aberrant Cu(2+) homeostasis. 

PMID- 24746620
TI  - Inductive differentiation of conjunctival goblet cells by gamma-secretase
      inhibitor and construction of recombinant conjunctival epithelium.
AB  - gamma-secretase inhibitor has been shown to promote intestinal goblet cell
      differentiation. We now demonstrated that the in vitro addition of gamma
      secretase inhibitor in the culture of human conjunctival epithelial cells
      significantly promoted the differentiation of conjunctival goblet cells with
      typical droplet-like phenotype, positive periodic acid-Schiff and goblet cell
      specific Muc5Ac, cytokeratin 7 and Helix pomatia agglutinin lectin staining.
      Moreover, topical application of gamma-secretase inhibitor promoted the
      differentiation of mouse conjunctival goblet cells in vivo. Furthermore, the
      expression of Notch target gene HES-1 was down-regulated during the
      differentiation of conjunctival goblet cells. In addition, we found that the
      recombinant conjunctival epithelium on amniotic membrane showed less goblet cell
      density and abnormal location when compared with normal conjunctival epithelium,
      which were improved by the addition of gamma-secretase inhibitor in the final
      induction.

PMID- 24746621
TI  - [Strong association between nicotine dependence symptoms and Cluster A
      personality disorder traits].

PMID- 24746622
TI  - [Impulsivity and externalization and internalization problems in adolescents].
AB  - OBJECTIVES: The multidimensional aspect of the concept of impulsivity is proven
      by the composite structure of the rating scales of impulsivity. Several studies
      have already found correlations between trait-impulsivity and externalizing
      disorders. However, the studies interested in the relationship between trait
      impulsivity and internalizing problems are rare. We have tried to explore
      correlations between impulsivity and externalization and internalization
      problems, in a population of adolescent outpatients. METHODS: We recruited 31
      adolescent out-patients in the child and adolescent psychiatry department in the
      University Hospital of Monastir, Tunisia. The Barratt Impulsivity Scale (BIS) was
      used to evaluate a multidimensional concept of trait-impulsivity, including the
      dimensions of "Motor", "Non-planning" and "Attentional" impulsivities. The
      Strength and Difficulties Scales (SDQ) was used to assess different domains of
      externalizing and internalizing problems, including "Emotional symptoms",
      "Conduct problems", "Hyperactivity" and "Peer problems". RESULTS: The sex-ratio
      was 1.21. The mean age was 15.19+/-1.27 years. All patients but one were
      attending school. The diagnosis was "Major Depressive Episode" in 32% and
      "Behavior Disorder" in 38%. The means of the scores of externalizing and
      internalizing problems were 9.35+/-4.41 and 9.65+/-3.26, respectively. The total
      score of the BIS was significantly related to both scores of externalizing and
      internalizing problems. The "Motor" impulsivity was specially correlated with the
      externalizing dimension of the SDQ. The non-planning impulsivity was correlated
      with both scores of externalizing and internalizing problems, but it was mainly
      related to internalizing problems. The attentional impulsivity was also
      correlated with both dimensions of externalizing and internalizing problems.
      CONCLUSION: The dimensions of trait-impulsivity were correlated with various
      dimensions of the SDQ concerning externalizing and internalizing problems. That
      confirms the hypothesis that the impulsiveness is associated with wide domains of
      the psychopathology of the teenager which are not limited to behavior disorders.
      We can process these problems by influencing the "Motor impulsivity" and "Non
      planning impulsivity". The cognitive and behavioral therapy and the selective
      serotonin reuptake inhibitor may be efficient.

PMID- 24746623
TI  - Hydrogels in a historical perspective: from simple networks to smart materials.
AB  - Over the past decades, significant progress has been made in the field of
      hydrogels as functional biomaterials. Biomedical application of hydrogels was
      initially hindered by the toxicity of crosslinking agents and limitations of
      hydrogel formation under physiological conditions. Emerging knowledge in polymer
      chemistry and increased understanding of biological processes resulted in the
      design of versatile materials and minimally invasive therapies. Hydrogel matrices
      comprise a wide range of natural and synthetic polymers held together by a
      variety of physical or chemical crosslinks. With their capacity to embed
      pharmaceutical agents in their hydrophilic crosslinked network, hydrogels form
      promising materials for controlled drug release and tissue engineering. Despite
      all their beneficial properties, there are still several challenges to overcome
      for clinical translation. In this review, we provide a historical overview of the
      developments in hydrogel research from simple networks to smart materials. 

PMID- 24746624
TI  - Cancer nanomedicine and the complement system activation paradigm: anaphylaxis
      and tumour growth.
AB  - A wide variety of nanocarriers and particularly cancer nanomedicines activate the
      complement system, which is the first line of the innate immune defence
      mechanism. Complement activation may induce inflammatory responses, but such
      responses arising from uncontrolled complement activation could be life
      threatening. Accordingly, the role of complement in initiation of adverse
      reactions to particulate and polymer therapeutics is receiving increasing
      attention. Furthermore, the involvement of complement-activation products in
      promoting tumour growth has also been indicated. This could be of serious concern
      for development of cancer nanomedicines and cancer nanotechnology initiatives.
      These concepts are reviewed with preliminary evidence that intra-tumoural
      accumulation of model long circulating nanoparticles could promote tumour growth.

PMID- 24746625
TI  - Induced pluripotent stem (iPS) cells: a new source for cell-based therapeutics?
AB  - The generation of induced pluripotent stem (iPS) cells from somatic cells by the
      ectopic expression of defined transcription factors has provided the regenerative
      medicine field with a new tool for cell replacement strategies. The advantages
      that these pluripotent cells can offer in comparison to other sources of stem
      cells include the generation of patient-derived cells and the lack of embryonic
      tissue while maintaining a versatile differentiation potential. The promise of
      iPS cell derivatives for therapeutic applications is encouraging albeit very
      early in development, with the first clinical study currently ongoing in Japan.
      Many challenges are yet to be circumvented before this technology can be
      clinically translated widely though. The delivery and expression of the
      reprogramming factors, the genomic instability, epigenetic memory and impact of
      cell propagation in culture are only some of the concerns. This article aims to
      critically discuss the potential of iPS cells as a new source of cell
      therapeutics. 

PMID- 24746626
TI  - Bioreducible polymers for therapeutic gene delivery.
AB  - Most currently available cationic polymers have significant acute toxicity
      concerns such as cellular toxicity, aggregation of erythrocytes, and entrapment
      in the lung capillary bed, largely due to their poor biocompatibility and non
      degradability under physiological conditions. To develop more intelligent
      polymers, disulfide bonds are introduced in the design of biodegradable polymers.
      Herein, the sustained innovations of biomimetic nano-sized constructs with
      bioreducible poly(disulfide amine)s demonstrate a viable clinical tool for the
      treatment of cardiovascular disease, anemia, diabetes, and cancer. 

PMID- 24746627
TI  - Gelatin carriers for drug and cell delivery in tissue engineering.
AB  - The ability of gelatin to form complexes with different drugs has been
      investigated for controlled release applications. Gelatin parameters, such as
      crosslinking density and isoelectric point, have been tuned in order to optimize
      gelatin degradation and drug delivery kinetics. In recent years, focus has
      shifted away from the use of gelatin in isolation toward the modification of
      gelatin with functional groups and the fabrication of material composites with
      embedded gelatin carriers. In this review, we highlight some of the latest work
      being performed in these areas and comment on trends in the field. Specifically,
      we discuss gelatin modifications for immune system evasion, drug stabilization,
      and targeted delivery, as well as gelatin composite systems based on ceramics,
      naturally-occurring polymers, and synthetic polymers. 

PMID- 24746628
TI  - Neocortical pCREB and BDNF expression under different modes of hypobaric hypoxia:
      role in brain hypoxic tolerance in rats.
AB  - Preconditioning with repetitive mild hypobaric hypoxia is known to increase
      tolerance of susceptible brain neurons to severe hypoxia, whereas a single trial
      of mild hypoxia has been ineffective. In the present study, the effects of three
      trial and one-trial hypobaric preconditioning on the expression of the protective
      transcription factor phosphorylated CREB (pCREB) and neurotrophin BDNF, before
      and after severe hypobaric hypoxia, have been comparatively studied in the
      neocortex of rats. As revealed by quantitative immunocytochemistry, the severe
      hypobaric hypoxia (180 Torr, 3h) substantially down-regulated the levels of pCREB
      and BDNF in cortical neurons assessed 24h after the treatment. One trial of mild
      hypoxia (360 Torr, 2h) also reduced by half the number of BDNF-expressing cells,
      but had no effect on pCREB expression in the neocortex. In contrast, the exposure
      to three trials of mild hypoxia at 24h intervals considerably up-regulated pCREB
      and BDNF levels in the neocortex of rats. Only preconditioning by three trials of
      mild hypoxia (360 Torr, 2h, 24h intervals), but not a single trial
      preconditioning, was neuroprotective significantly enhancing the pCREB and BDNF
      neuronal expression in response to severe hypoxic challenge. The results of the
      present study indicate that development of the neuronal hypoxic tolerance induced
      by the three-trial mild hypoxic preconditioning is apparently associated with
      activation of CREB and BDNF expression.

PMID- 24746630
TI  - Laryngeal chondrosarcoma diagnosed by core-needle biopsy.
AB  - We report a case of chondrosarcoma of the larynx, diagnosed by a percutaneous
      core-needle biopsy (CNB). Cartilaginous tumors of the larynx are usually
      diagnosed by biopsy with direct laryngomicroscopy under general anesthesia.
      However, patients find it difficult to undergo a biopsy under general anesthesia,
      for physical, economic, and social reasons. Instead, we can readily detect and
      sample tumors of the larynx using ultrasound under local anesthesia with reduced
      stress. Concerning needle-puncture biopsies, including fine-needle aspiration
      cytology (FNAC) and CNB, some studies have reported needle track dissemination, a
      possible complication in patients with malignant tumors. Thus, in the head and
      neck region, we generally use FNAC for biopsies, not CNB. However, it can be
      difficult to diagnose bone tumors by cytology alone. Regarding primary bone
      tumors, only one study has reported needle track dissemination by CNB, in
      osteosarcoma of the femur. Additionally, this complication has not been reported
      before with chondrosarcoma anywhere in the body. To our knowledge, this is the
      first report concerning chondrosarcoma of the larynx diagnosed by percutaneous
      CNB. We recommend CNB as a useful and safe diagnostic technique for primary bone
      tumors in the head and neck region. 

PMID- 24746629
TI  - Idiopathic pulmonary fibrosis: early detection and referral.
AB  - Idiopathic pulmonary fibrosis (IPF), a devastating progressive interstitial lung
      disease (ILD) with no known cause or cure, is the most common and deadly of the
      idiopathic interstitial pneumonias. With a median survival of 3-5 years following
      diagnosis, IPF is characterized by a progressive decline in lung function and
      quality of life in most patients. Vigilance among clinicians in recognizing IPF
      early in the disease course remains critical to properly caring for these
      patients, as this provides the widest range of management options. When IPF is
      suspected, a multidisciplinary evaluation (MDE) by a clinician, radiologist and
      pathologist with ILD expertise should occur, as this improves diagnostic
      agreement in both community and academic settings. When community MDE is not
      possible, or diagnostic doubt exists, referral to an ILD center should be
      considered. ILD center referral may also provide access specialized care,
      including clinical trials and lung transplantation, and should be considered for
      any patient with an established diagnosis of IPF. 

PMID- 24746631
TI  - Amniotic membrane in reconstruction of larynx following chondrosarcoma resection:
      a case report.
AB  - Chondrosarcomas of the larynx are rare malignancies and frequently located in
      cricoid cartilage. They are characterized by a low tendency to metastasis (low
      grade type). The treatment of choice is surgery, which may be endoscopic or open
      partial surgery, if extension of the cancer is limited. Prognosis is generally
      good. In this report, a case of low grade chondrosarcoma of the larynx is
      presented, which was treated surgically with a combined use of amniotic membrane
      and stent in airway reconstruction following laryngofissure approach for
      resection of the tumor. 

PMID- 24746632
TI  - Recent onset disequilibrium mimicking acute vestibulopathy in early multiple
      sclerosis.
AB  - The differential diagnosis of patients with acute unilateral vestibulopathy rests
      in the proper clinical assessment and use of selected tests of vestibular
      function. In case of a central nervous system lesion as in Multiple Sclerosis,
      the case shown here, it is of particular importance to observe congruency between
      severity of symptoms and signs and, of topographic diagnosis. We report a case of
      a 37-year-old woman with recent onset disequilibrium that after careful analysis
      of the different test results several incongruences were found; this prompted a
      radiological study that provided the clue to diagnosis. After treatment the
      patient recovered completely not only clinically but also in vestibular deficit.

PMID- 24746633
TI  - Incidentally detected middle ear osteoma: two cases reports and literature
      review.
AB  - Osteomas of the middle ear are rare benign neoplasms. To date, only a few cases
      have been reported. Osteomas of the middle ear are small, single, usually
      unilateral, peduncular growths, off-white in color, with a smooth or multilobular
      surface, asymptomatic or causing functional disorders. The most common symptom is
      conductive hearing loss because of impingement of the ossicular chain. Some cases
      are asymptomatic and are diagnosed incidentally. We present two cases of
      incidentally detected middle ear osteoma. Based on a review of the main articles
      in the literature and analysis of two cases managed in our department, we
      describe the clinical spectrum, etiology, and management of middle ear osteomas. 

PMID- 24746634
TI  - GCN5 is involved in regulation of immunoglobulin heavy chain gene expression in
      immature B cells.
AB  - GCN5 is involved in the acetylation of core histones, which is an important
      epigenetic event for transcriptional regulation through alterations in the
      chromatin structure in eukaryotes. To investigate physiological roles of GCN5, we
      have systematically analyzed phenotypes of homozygous GCN5-deficient DT40
      mutants. Here, we report participation of GCN5 in regulation of IgM heavy chain
      (H-chain) gene expression. GCN5-deficiency down-regulates gene expressions of IgM
      H-chain (as whole, membrane-bound and secreted forms of its mRNA) but not light
      chain (L-chain), causing decreases in membrane-bound and secreted forms of IgM
      proteins. Chromatin immnoprecipitation assay revealed that GCN5 binds to the
      chicken IgM H-chain gene around its constant region but not L-chain gene, and
      acetylate Lys-9 residues of histone H3 within chromatin surrounding the constant
      region. These results suggest that GCN5 takes part in transcriptional regulation
      of the IgM H-chain gene via histone acetylation resulting in formation of relaxed
      chromatin arrangement around its coding region and plays a key role in epigenetic
      regulation of B cell functions. 

PMID- 24746635
TI  - Evidence for the coevolution of axon guidance molecule Netrin and its receptor
      Frazzled.
AB  - Coevolution of a ligand and its receptor is critical for maintaining their
      function in different species, but how ligand and its receptor coevolve is poorly
      understood. The axon guidance molecule Netrin and its receptor Frazzled (Fra) are
      useful to study the mechanisms of ligand-receptor coevolution. Here, we have
      applied codon substitution models to identify positive selection of the netrin
      and fra genes. The sites under positive selection in netrin and fra were detected
      in same lineage, such as nematode, dipteran, hymenopteran, hemichordate, and
      teleost. Several amino acid residues that are under positive selection were
      identified in the interaction domains. Here we provide evidence that positive
      selection is essential for the coevolution of Netrin and Fra during central
      nervous system evolution. 

PMID- 24746636
TI  - Right ventricular unloading and respiratory support with a wearable artificial
      pump-lung in an ovine model.
AB  - BACKGROUND: Device availability of mechanical circulatory or respiratory support
      to the right heart has been limited. The purpose of this study was to investigate
      the effect of right heart unloading and respiratory support with a wearable
      integrated artificial pump-lung (APL). METHODS: The APL device was placed
      surgically between the right atrium and pulmonary artery in 7 sheep. Anti
      coagulation was performed with heparin infusion. The device's ability to unload
      the right ventricle (RV) was investigated by echocardiograms and right heart
      catheterization at different bypass flow rates. Hemodynamics and
      echocardiographic data were evaluated. APL flow and gas transfer rates were also
      measured at different device speeds. RESULTS: Hemodynamics remained stable during
      APL support. There was no significant change in systemic blood pressure and
      cardiac index. Central venous pressure, RV pressure, RV end-diastolic dimension
      and RV ejection fraction were significantly decreased when APL device flow rate
      approached 2 liters/min. Linear regression showed significant correlative trends
      between the hemodynamic and cardiac indices and device speed. The oxygen transfer
      rate increased with device speed. The oxygen saturation from the APL outlet was
      fully saturated (>95%) during support. The impact of APL support on blood
      elements (plasma free hemoglobin and platelet activation) was minimal.
      CONCLUSIONS: APL device support significantly unloaded the RV with increasing
      device speed. The device also provided stable hemodynamics and respiratory
      support in terms of blood flow and oxygen transfer. The right heart unloading
      performance of this wearable device needs to be evaluated further in an animal
      model of right heart failure with long-term support.

PMID- 24746638
TI  - Retrograde coronary vein infusion of cardiac explant-derived c-Kit+ cells
      improves function in ischemic heart failure.
AB  - BACKGROUND: Progenitor cells isolated from cardiac explant-derived cells improve
      cardiac function after myocardial infarction (MI). To fully realize the
      therapeutic potential of these cells, it is essential to develop a safe and
      efficient delivery method. Therefore, the objective of this study was to
      determine the efficacy of our newly developed approach to retrograde coronary
      vein (RCV) infusion of cardiac c-Kit(+) cells in a small-animal model of
      congestive heart failure (CHF). METHODS: Sprague-Dawley rats underwent
      experimental MI. After 21 days, cardiac explant-derived c-Kit(+) cells were
      delivered to both sham and CHF animals using RCV delivery. Vehicle-treated (serum
      free medium) sham and CHF animals were used as controls. Cardiac function and
      heart tissues were evaluated 21 days post-transplantation. RESULTS: RCV-delivered
      cells were retained in infarcted hearts for at least 21 days after
      transplantation. At 21 days post-RCV infusion, the majority of transplanted c
      Kit(+)/GFP(+) cells were localized in the left ventricle. Compared with vehicle
      treated CHF animals, RCV-treated rats showed a significant improvement in cardiac
      function. Furthermore, RCV-treated rats exhibited an increase in capillary
      density, a decrease in total heart collagen, and a reduction in both infarct size
      and cardiomyocyte hypertrophy when compared with vehicle-treated CHF rats.
      CONCLUSIONS: Our study showed that the RCV infusion approach is an efficient
      technique for targeted cell delivery to the infarcted myocardium. Cardiac c
      Kit(+) cells, delivered using RCV infusion ameliorated progression of heart
      failure, improved cardiac function and retarded myocardial remodeling in heart
      failure rats.

PMID- 24746637
TI  - Post-approval study of a highly pulsed, low-shear-rate, continuous-flow, left
      ventricular assist device, EVAHEART: a Japanese multicenter study using J-MACS.
AB  - BACKGROUND: The EVAHEART left ventricular assist device was approved in 2010 by
      the Japanese Pharmaceuticals and Medical Devices Agency (PMDA) for bridge to
      heart transplantation (BTT). However, its effectiveness has not been evaluated
      since approval. In this study we evaluated the EVAHEART device in a commercial
      setting in Japan. METHODS: Ninety-six consecutive patients enrolled in the
      Japanese Registry for Mechanically Assisted Circulatory Support (J-MACS), who
      were listed for transplant or likely to be listed and who received an EVAHEART
      device, were enrolled from 2011 to 2013 at 14 Japanese centers. Patients'
      survival rates, adverse events and quality-of-life data were obtained from the J
      MACS Registry. RESULTS: Patients' median age was 43 years (85% male). The
      Interagency Registry for Mechanically Assisted Circulatory Support profiles
      revealed 12 patients in Level 1, 45 in Level 2, 37 in Level 3 and 1 in Level 4.
      The mean support duration was 384.7 days, with a cumulative duration of 101.2
      years. The Kaplan-Meier survival rate during support was 93.4% at 6 months, 87.4%
      at 1 year and 87.4% at 2 years. Seventy-seven patients (80.2%) currently remain
      on support, 7 received a transplant and 10 died during support. Major adverse
      events included drive-line infection (14.6%) and neurologic events such as
      ischemic stroke (17.7%), hemorrhage (13.5%), transient ischemic attack (3.1%),
      pump thrombosis (1%) and hemolysis (1%). There was no gastrointestinal (GI)
      bleeding or right heart failure requiring right ventricular assist device (RVAD).
      There was no pump exchange due to mechanical failure. CONCLUSIONS: The EVAHEART
      device provides safe, reliable and long-term circulatory support with improved
      survival in commercial settings of BTT in Japan, where the transplant waiting
      period is much longer. Incidences of GI bleeding, hemolysis, right ventricular
      failure, device thrombosis and mechanical failure were extremely rare in patients
      on EVAHEART devices.

PMID- 24746639
TI  - The effect of recombinant sTGFbeta1RII and sIL13Ralpha2 receptor proteins on
      schistosomiasis japonica, hepatic fibrosis and signal transduction in a mouse
      model of schistosome disease.
AB  - This study was designed to investigate the effect of recombinant sTGFbeta1RII and
      sIL13Ralpha2 receptor proteins on schistosomiasis japonica, hepatic fibrosis and
      the expression of SMAD3 and STAT6. The proteins sTGFbeta1RII and sIL13Ralpha2
      were expressed in Escherichiacoli, purified using affinity chromatography and
      characterized by Western blotting. Female BALB/C mice (48) were randomly divided
      into eight groups and infected with Schistosoma japonicum. Five weeks after
      infection, test groups were injected with the recombinant proteins at different
      doses. Eight weeks after infection, lung and hepatic tissue samples were obtained
      and stained with hematoxylin and eosin (HE) and Masson's trichrome.
      Immunohistochemical staining was used to detect the expression of SMAD3 and
      STAT6. The recombinant proteins sTGFbeta1RII and sIL13Ralpha2 were successfully
      expressed, purified, and characterized. The granuloma area, hepatic
      hydroxyproline (HYP) level and hepatic fibrosis of the protein therapeutic groups
      were significantly smaller than those of the positive control group (P<0.01).
      Treatment with sTGFbeta1RII was more effective when the protein was administered
      for 4weeks rather than 2 (P<0.01). Hepatic fibrosis in the groups using a low
      dose of protein sTGFbeta1 was lower that of the combination group (P<0.05). The
      expression level of STAT6 was significantly lower in groups treated with
      sIL13Ralpha2 than in groups not treated with the protein (P<0.01). The
      recombinant proteins TGFbeta1RII and sIL13Ralpha2 were able to decrease granuloma
      area and hepatic fibrosis in schistosomiasis japonica, and also reduced the
      expression of the signal transduction proteins SMAD3 and STAT6. The proteins were
      more effective when used in combination than when applied singly. 

PMID- 24746640
TI  - Effects of Microtus fortis lymphocytes on Schistosoma japonicum in a bone marrow
      transplantation model.
AB  - Microtus fortis is a non-permissive host for Schistosoma japonicum. While M.
      fortis lymphocytes are known to provide natural resistance against S. japonicum,
      the specific mechanism remains unclear. A bone marrow transplantation (BMT) model
      was established using immunodeficient mice, either nude (experiment 1) or V(D)J
      recombination activation gene deficient mice (RAG-1(-/-)) (experiment 2) as
      recipients and M. fortis or C57BL/6 mice as donors. The growth and development of
      S. japonicum were evaluated in each group to assess the role of M. fortis
      lymphocytes in the response to infection. Lymphocyte ratios and S. japonicum
      specific antibody production in transplanted groups increased significantly
      compared to those in non-transplanted group. Spleen indices and density of
      splenic lymphocytes in transplanted RAG-1(-/-) mice were higher than those in non
      transplanted RAG-1(-/-) mice. No difference in the worm burden was observed among
      group A (transplants derived from M. fortis), B (transplants derived from C57BL/6
      mouse) and C (non-transplanted mice), although worms in group A were shorter than
      those in other groups, except non-transplanted RAG-1(-/-) mice. Reproductive
      systems of worms in mice (nude or RAG-1(-/-)) transplanted from M. fortis were
      not as mature as those in mice (nude or RAG-1(-/-)) transplanted from C57BL/6
      mouse and non-transplanted nude mice, but they were more mature than worms in non
      transplanted RAG-1(-/-) mice. Therefore, the transplantation model using nude and
      RAG-1(-/-) mice was successfully established. The M. fortis lymphocytes did not
      appear to affect the S. japonicum worm burden, but they led to schistosome
      shortening and a significant reduction in parasite spawning. Thus, M. fortis
      cellular and humoral immunity provides a defense against schistosomes by
      negatively impacting the parasite growth and reproductive development. 

PMID- 24746642
TI  - Governance versus government: drug consumption rooms in Australia and the UK.
AB  - AIM: To evaluate, through a case study, the extent to which elements of
      governance and elements of government are influential in determining the
      implementation or non-implementation of a drugs intervention. METHODS:
      Comparative analysis of the case of a drug consumption room in the UK (England)
      and Australia (New South Wales), including 16 semi-structured interviews with key
      stakeholders and analysis of relevant documents according to characteristic
      features of governance and government (power decentralisation, power
      centralisation, independent self-organising policy networks, use of evidence, top
      down steering/directing, legislation). RESULTS: Characteristic features of both
      governance and government are found in the data. Elements of governance are more
      prominent in New South Wales, Australia than in England, UK, where government
      prevails. Government is seen as the most important actor at play in the making,
      or absence, of drug consumption rooms. CONCLUSIONS: Both governance and
      government are useful frameworks in conceptualising the policy process. The
      governance narrative risks overlooking the importance of traditional government
      structures. In the case of drug consumption rooms in the UK and Australia, a
      focus on government is shown to have been crucial in determining whether the
      intervention was implemented.

PMID- 24746641
TI  - Ketamine exposure in early development impairs specification of the primary germ
      cell layers.
AB  - Preclinical and clinical evidence implicates N-methyl-d-aspartate receptor
      (NMDAr) signaling in early embryological development. However, the role of NMDAr
      signaling in early development has not been well studied. Here, we use a mouse
      embryonic stem cell model to perform a step-wise exploration of the effects of
      NMDAr signaling on early cell fate specification. We found that antagonism of the
      NMDAr impaired specification into the neuroectodermal and mesoendodermal cell
      lineages, with little or no effect on specification of the extraembryonic
      endoderm cell lineage. Consistent with these findings, exogenous NMDA promoted
      neuroectodermal differentiation. Finally, NMDAr antagonism modified expression of
      several key targets of TGF-beta superfamily signaling, suggesting a mechanism for
      these findings. In summary, this study shows that NMDAr antagonism interferes
      with the normal developmental pathways of embryogenesis, and suggests that
      interference is most pronounced prior to neuroectodermal and mesoendodermal cell
      fate specification. 

PMID- 24746643
TI  - VCAM-1 specific PEGylated SAINT-based lipoplexes deliver siRNA to activated
      endothelium in vivo but do not attenuate target gene expression.
AB  - In recent years much research in RNA nanotechnology has been directed to develop
      an efficient and clinically suitable delivery system for short interfering RNA
      (siRNA). The current study describes the in vivo siRNA delivery using PEGylated
      antibody-targeted SAINT-based-lipoplexes (referred to as antibody
      SAINTPEGarg/PEG2%), which showed superior siRNA delivery capacity and effective
      down-regulation of VE-cadherin gene expression in vitro in inflammation-activated
      primary endothelial cells of different vascular origins. PEGylation of antibody
      SAINTPEGarg resulted in more desirable pharmacokinetic behavior than that of non
      PEGylated antibody-SAINTPEGarg. To create specificity for inflammation-activated
      endothelial cells, antibodies against vascular cell adhesion molecule-1 (VCAM-1)
      were employed. In TNFalpha-challenged mice, these intravenously administered anti
      VCAM-1-SAINTPEGarg/PEG2% homed to VCAM-1 protein expressing vasculature. Confocal
      laser scanning microscopy revealed that anti-VCAM-1-SAINTPEGarg/PEG2% co
      localized with endothelial cells in lung postcapillary venules. Furthermore, they
      did not exert any liver and kidney toxicity. Yet, lack of in vivo gene silencing
      as assessed in whole lung and in laser microdissected lung microvascular segments
      indicates that in vivo internalization and/or intracellular trafficking of the
      delivery system and its cargo in the target cells are not sufficient, and needs
      further attention, emphasizing the essence of evaluating siRNA delivery systems
      in an appropriate in vivo animal model at an early stage in their development.

PMID- 24746644
TI  - Single molecule studies of DNA mismatch repair.
AB  - DNA mismatch repair, which involves is a widely conserved set of proteins, is
      essential to limit genetic drift in all organisms. The same system of proteins
      plays key roles in many cancer related cellular transactions in humans. Although
      the basic process has been reconstituted in vitro using purified components, many
      fundamental aspects of DNA mismatch repair remain hidden due in part to the
      complexity and transient nature of the interactions between the mismatch repair
      proteins and DNA substrates. Single molecule methods offer the capability to
      uncover these transient but complex interactions and allow novel insights into
      mechanisms that underlie DNA mismatch repair. In this review, we discuss
      applications of single molecule methodology including electron microscopy, atomic
      force microscopy, particle tracking, FRET, and optical trapping to studies of DNA
      mismatch repair. These studies have led to formulation of mechanistic models of
      how proteins identify single base mismatches in the vast background of matched
      DNA and signal for their repair. 

PMID- 24746646
TI  - Validity of estimated glomerular filtration rates for assessment of renal
      function after renal artery stenting in patients with atherosclerotic renal
      artery stenosis.
AB  - OBJECTIVES: The purpose of this study was to evaluate the validity of estimates
      of glomerular filtration rate (eGFR) for assessing serial changes in renal
      function after renal artery stenting. BACKGROUND: eGFR are unreliable for
      assessing serial renal function in patients with atherosclerotic renal artery
      stenosis (RAS). eGFR have not been validated for assessment of serial renal
      function after renal artery stenting. METHODS: Serum creatinine (SCr) and (125)I
      iothalamate GFR (iGFR) were measured in RAS patients before and after renal
      artery stenting. eGFR were calculated from Modification of Diet in Renal Disease
      (MDRD), Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI), and
      Cockcroft-Gault (CG) formulas. Using iGFR as the reference standard, the
      sensitivity, specificity, and area under the receiver-operating characteristic
      curve (AUC) were determined for MDRD, CKD-EPI, and CG for assessing changes in
      GFR before and after intervention. RESULTS: Between 1998 and 2007, 84 patients
      underwent iGFR and eGFR before and after renal artery stenting. All eGFR
      demonstrated poor sensitivity and reliability for detecting >=20% changes in
      iGFR, and poor agreement in the magnitude and direction of change in iGFR, before
      and after renal stenting. CONCLUSIONS: In RAS patients, eGFR demonstrate poor
      sensitivity and reliability for detecting meaningful changes in iGFR after renal
      artery stenting. eGFR should be abandoned as primary endpoints in major clinical
      trials assessing the impact of renal revascularization on renal function.

PMID- 24746645
TI  - DNA double-strand break repair pathway choice and cancer.
AB  - Since DNA double-strand breaks (DSBs) contribute to the genomic instability that
      drives cancer development, DSB repair pathways serve as important mechanisms for
      tumor suppression. Thus, genetic lesions, such as BRCA1 and BRCA2 mutations, that
      disrupt DSB repair are often associated with cancer susceptibility. In addition,
      recent evidence suggests that DSB "mis-repair", in which DSBs are resolved by an
      inappropriate repair pathway, can also promote genomic instability and presumably
      tumorigenesis. This notion has gained currency from recent cancer genome
      sequencing studies which have uncovered numerous chromosomal rearrangements
      harboring pathological DNA repair signatures. In this perspective, we discuss the
      factors that regulate DSB repair pathway choice and their consequences for genome
      stability and cancer. 

PMID- 24746647
TI  - Coronary artery bypass graft surgery versus percutaneous coronary intervention
      with first-generation drug-eluting stents: a meta-analysis of randomized
      controlled trials.
AB  - OBJECTIVES: This study sought to compare the efficacy of coronary artery bypass
      graft surgery (CABG) to that of percutaneous coronary intervention (PCI) with
      first-generation drug-eluting stents among patients with multivessel disease
      (MVD), unprotected left main (LM) disease, and single-vessel proximal left
      anterior descending (LAD) disease. BACKGROUND: The efficacy and safety of CABG
      versus PCI with drug-eluting stents in patient subgroups remains controversial.
      METHODS: We systematically searched Cardiosource, Circulation,
      Clinicaltrials.gov, the Cochrane Library, EMBASE, and Medline for articles
      published through June 2013 for randomized controlled trials comparing CABG with
      PCI. Primary endpoints included mortality, myocardial infarction,
      revascularization, and stroke. Data were meta-analyzed with random-effects
      models. RESULTS: We identified 7 randomized controlled trials (N = 5,835): 2 of
      MVD (n = 2,410, 100% diabetic), 2 of LM disease (n = 1,206, 29.0% diabetic), 1 of
      3-vessel or LM disease (n = 1,900, 25.5% diabetic), and 2 of single-vessel
      proximal LAD disease (n = 319, 36.3% diabetic). In MVD patients, CABG reduced the
      risk of mortality (risk ratio [RR]: 0.70, 95% confidence interval [CI]: 0.57 to
      0.87), myocardial infarction (RR: 0.47, 95% CI: 0.36 to 0.61), and repeat
      revascularization (RR: 0.36, 95% CI: 0.24 to 0.52), but increased stroke risk
      (RR: 1.72, 95% CI: 1.02 to 2.90). In patients with LM disease, CABG reduced
      revascularization risk (RR: 0.60, 95% CI: 0.46 to 0.78) and increased stroke risk
      (RR: 2.89, 95% CI: 1.15 to 7.27). Data for patients with single-vessel proximal
      LAD disease were inconclusive. CONCLUSIONS: CABG is more efficacious than is PCI
      with first-generation drug-eluting stents in patients with LM and MVD, at the
      cost of increased rates of stroke. No conclusion can be drawn for patients with
      single-vessel proximal LAD disease.

PMID- 24746648
TI  - Angina pectoris and myocardial ischemia in the absence of obstructive coronary
      artery disease: practical considerations for diagnostic tests.
AB  - Angina and myocardial ischemia without obstructive coronary artery disease are
      common clinical findings, often neglected for the assumption of a good prognosis.
      Most often, such patients are neither further investigated nor offered specific
      treatment beyond reassurance. However, the absence of significant coronary
      stenoses on angiography does not necessarily imply a "healthy" coronary tree. In
      such cases, myocardial ischemia may result from different types of functional
      disease involving the epicardial coronary arteries, the coronary
      microcirculation, or both; an accurate assessment of these components should be
      systematically performed after exclusion of organic epicardial disease because a
      correct diagnosis has relevant prognostic and therapeutic implications. Here we
      discuss the basic principles of diagnostic tests in this setting and propose a
      diagnostic sequence of reasonable practical implementation that may help identify
      patients at risk of future cardiac events.

PMID- 24746649
TI  - Effectiveness of low rate fluoroscopy at reducing operator and patient radiation
      dose during transradial coronary angiography and interventions.
AB  - OBJECTIVES: This study sought to determine the efficacy of low rate fluoroscopy
      at 7.5 frames/s (FPS) versus conventional 15 FPS for reduction of operator and
      patient radiation dose during diagnostic coronary angiography (DCA) and
      percutaneous coronary intervention (PCI) via the transradial approach (TRA).
      BACKGROUND: TRA for cardiac catheterization is potentially associated with
      increased radiation exposure. Low rate fluoroscopy has the potential to reduce
      radiation exposure. METHODS: Patients undergoing TRA diagnostic angiography +/-
      ad-hoc PCI were randomized to fluoroscopy at 7.5 FPS versus 15 FPS prior to the
      procedure. Both 7.5 and 15 FPS fluoroscopy protocols were configured with a fixed
      dose per pulse of 40 nGy. Primary endpoints were operator radiation dose
      (measured with dosimeter attached to the left side of the thyroid shield in
      MUSievert [MUSv]), patient radiation dose (expressed as dose-area product in
      Gy.cm(2)), and fluoroscopy time. RESULTS: From October 1, 2012 to August 30,
      2013, from a total of 363 patients, 184 underwent DCA and 179 underwent PCI.
      Overall, fluoroscopy at 7.5 FPS compared with 15 FPS was associated with a
      significant reduction in operator dose (30% relative reduction [RR], p < 0.0001);
      and in patient's dose-area product (19% RR; p = 0.022). When stratified by
      procedure type, 7.5 FPS compared with 15 FPS was associated with significant
      reduction in operator dose during both DCA (40% RR; p < 0.0001) and PCI (28% RR;
      p = 0.0011). Fluoroscopy at 7.5 FPS, compared with 15 FPS, was also associated
      with substantial reduction in patients' dose-area product during DCA (26% RR; p =
      0.0018) and during PCI (19% RR; p = 0.13). Fluoroscopy time was similar in 7.5
      FPS and 15 FPS groups for DCA (3.4 +/- 2.0 min vs. 4.0 +/- 4.7 min; p = 0.42) and
      PCI (11.9 +/- 8.4 min vs. 13.3 +/- 9.7 min; p = 0.57), respectively. CONCLUSIONS:
      Fluoroscopy at 7.5 FPS, compared with 15 FPS, is a simple and effective method in
      reducing operator and patient radiation dose during TRA DCA and PCI.

PMID- 24746651
TI  - Revascularization decisions in coronary artery disease: hitting a moving target.

PMID- 24746650
TI  - 1-year clinical outcomes of diabetic patients treated with everolimus-eluting
      bioresorbable vascular scaffolds: a pooled analysis of the ABSORB and the SPIRIT
      trials.
AB  - OBJECTIVES: The aim of this study was to evaluate 1-year clinical outcomes of
      diabetic patients treated with the Absorb bioresorbable vascular scaffold (BVS).
      BACKGROUND: Clinical outcomes of diabetic patients after BVS implantation have
      been unreported. METHODS: This study included 101 patients in the ABSORB Cohort B
      trial and the first consecutive 450 patients with 1 year of follow-up in the
      ABSORB EXTEND trial. A total of 136 diabetic patients were compared with 415
      nondiabetic patients. In addition, 882 diabetic patients treated with everolimus
      eluting metal stents (EES) in pooled data from the SPIRIT trials (SPIRIT FIRST
      [Clinical Trial of the Abbott Vascular XIENCE V Everolimus Eluting Coronary Stent
      System], SPIRIT II [A Clinical Evaluation of the XIENCE V Everolimus Eluting
      Coronary Stent System], SPIRIT III [Clinical Trial of the XIENCE V Everolimus
      Eluting Coronary Stent System (EECSS)], SPIRIT IV Clinical Trial [Clinical
      Evaluation of the XIENCE V Everolimus Eluting Coronary Stent System]) were used
      for the comparison by applying propensity score matching. The primary endpoint
      was a device-oriented composite endpoint (DoCE), including cardiac death, target
      vessel myocardial infarction, and target lesion revascularization at 1-year
      follow-up. RESULTS: The cumulative incidence of DoCE did not differ between
      diabetic and nondiabetic patients treated with the BVS (3.7% vs. 5.1%, p = 0.64).
      Diabetic patients treated with the BVS had a similar incidence of the DoCE
      compared with diabetic patients treated with EES in the matched study group (3.9%
      for the BVS vs. 6.4% for EES, p = 0.38). There were no differences in the
      incidence of definite or probable scaffold/stent thrombosis (0.7% for both
      diabetic and nondiabetic patients with the BVS; 1.0% for diabetic patients with
      the BVS vs. 1.7% for diabetic patients with EES in the matched study group).
      CONCLUSIONS: In the present analyses, diabetic patients treated with the BVS
      showed similar rates of DoCEs compared with nondiabetic patients treated with the
      BVS and diabetic patients treated with EES at 1-year follow-up. (ABSORB Clinical
      Investigation, Cohort B; NCT00856856; ABSORB EXTEND Clinical Investigation;
      NCT01023789; Clinical Trial of the Abbott Vascular XIENCE V Everolimus Eluting
      Coronary Stent System [SPIRIT FIRST]; NCT00180453; A Clinical Evaluation of the
      XIENCE V Everolimus Eluting Coronary Stent System [SPIRIT II]; NCT00180310;
      Clinical Trial of the XIENCE V Everolimus Eluting Coronary Stent System [EECSS]
      [SPIRIT III]; NCT00180479; Clinical Evaluation of the XIENCE V Everolimus Eluting
      Coronary Stent System [SPIRIT IV Clinical Trial]; NCT00307047).

PMID- 24746652
TI  - Relationship of beam angulation and radiation exposure in the cardiac
      catheterization laboratory.
AB  - OBJECTIVES: The aim of this study was to analyze the relationship between beam
      angulation and air kerma in a modern cardiac catheterization laboratory.
      BACKGROUND: Recent reports have identified the merits of reducing radiation
      scatter, an important determinant of radiation dose in the catheterization
      laboratory. Radiation scatter is poorly characterized in the context of
      catheterization laboratories using modern digital equipment. Understanding the
      principles of dosimetry may reduce the radiation exposure to patients, providers,
      and medical staff. METHODS: Prospectively captured radiation data were extracted
      from a database of 1,975 diagnostic catheterizations (DCs) and 755 percutaneous
      coronary interventions (PCIs), which included 138,342 fluoroscopic and 35,440
      acquisition (cine) sequences. Fluoroscopy and acquisition modes were categorized
      into tertiles based on the total air kerma measured at a standard reference
      point. Radiation maps were modeled according to the relative proportion of
      exposure in each projection. RESULTS: Median air kerma during DCs and PCIs was
      677 and 2,188 mGy, respectively. Fluoroscopy contributed to 66.3% of total dose
      during PCIs compared with 39.7% during DCs (p < 0.001). Fluoroscopy was more
      sensitive to changes in angulation with a rapid increase in total air kerma on
      small increases in beam angulation. Complex spatial maps were created to study
      the impact of angulation and other covariates on total air kerma. Besides beam
      angulation, body surface area was the strongest predictor of the total air kerma.
      CONCLUSIONS: This study uniquely describes radiation dosimetry using contemporary
      equipment in a real-world setting. Extreme angulations were associated with high
      air kerma values. Fluoroscopy compared with acquisition was more sensitive to
      changes in angulation, with relatively larger increases in total air kerma with
      small increases in steepness of the angulation.

PMID- 24746653
TI  - In-stent protrusion after implantation of a drug-eluting stent in a honeycomb
      like coronary artery structure: complete resolution over 6 months and the role of
      optical coherence tomography imaging in the diagnosis and follow-up.

PMID- 24746654
TI  - Feasibility and efficacy of bioresorbable vascular scaffolds use for the
      treatment of in-stent restenosis and a bifurcation lesion in a heavily calcified
      diffusely diseased vessel.

PMID- 24746655
TI  - Radiation dose reduction in the cardiac catheterization laboratory utilizing a
      novel protocol.
AB  - OBJECTIVES: This study reports the results a novel radiation reduction protocol
      (RRP) system for coronary angiography and interventional procedures and the
      determinants of radiation dose. BACKGROUND: The cardiac catheterization
      laboratory is an important source of radiation and should be kept in good working
      order with dose-reduction and monitoring capabilities. METHODS: All diagnostic
      coronary angiograms and percutaneous coronary interventions from a single
      catheterization laboratory were analyzed 2 months before and after RRP
      implementation. The primary outcome was the relative dose reduction at the
      interventional reference point. Separate analyses were done for conventional 15
      frames/s (FPS) and at reduced 7.5 FPS post-RRP groups. RESULTS: A total of 605
      patients underwent coronary angiography (309 before RRP and 296 after RRP), with
      129 (42%) and 122 (41%) undergoing percutaneous coronary interventions before and
      after RRP, respectively. With RRP, a 48% dose reduction (1.07 +/- 0.05 Gy vs.
      0.56 +/- 0.03 Gy, p < 0.0001) was obtained, 35% with 15 FPS RRP (0.70 +/- 0.05
      Gy, p < 0.0001) and 62% with 7.5 FPS RRP (0.41 +/- 0.03 Gy, p < 0.001). Similar
      dose reductions for diagnostic angiograms and percutaneous coronary interventions
      were noted. There was no change in the number of stents placed or vessels
      intervened on. Increased dose was associated with male sex, radial approach,
      increasing body mass index, cine runs, and frame rates. Using a multivariable
      model, a 48% relative risk with RRP (p < 0.001), 44% with 15 FPS RRP and 68% with
      7.5 FPS RRP was obtained. CONCLUSIONS: We demonstrate a highly significant 48.5%
      adjusted radiation dose reduction using a novel algorithm, which needs strong
      consideration among interventional cardiology practice.

PMID- 24746656
TI  - Anatomic stabilization and functional normalization of a ruptured coronary plaque
      12 months after implantation of a bioresorbable scaffold.

PMID- 24746657
TI  - The learning curve in percutaneous repair of paravalvular prosthetic
      regurgitation: an analysis of 200 cases.
AB  - OBJECTIVES: This study sought to assess the learning curve for percutaneous
      repair of paravalvular prosthetic regurgitation. BACKGROUND: Percutaneous repair
      of prosthetic paravalvular regurgitation is a complex procedure. There is a
      paucity of data on the professional experience and tools needed to achieve
      optimal clinical outcomes. METHODS: We examined the chronological experience of
      200 patients (age 66 +/- 13 years; 57% men) who underwent percutaneous closure of
      paravalvular prosthetic regurgitation at our institution. A sequence number of
      the patient was assigned as a continuous variable for analysis. RESULTS: A total
      of 243 paravalvular defects (74% mitral; 26% aortic) were treated. Device
      delivery was successful in 92% with an average procedural time of 139 +/- 47 min.
      The 30-day rate of major adverse cardiovascular events was 7%. With increased
      case experience and adoption of dedicated imaging and catheter techniques, there
      were decreases in procedural time, fluoroscopy time, contrast volume
      administered, length of hospital stay, and major adverse cardiovascular events.
      Procedural success remained unchanged throughout the experience. The predominant
      reason for procedural failure was prosthetic leaflet impingement, which accounted
      for 9 of 21 failed cases. CONCLUSIONS: In this single-center experience, there
      was evidence of a learning curve that occurred with the adoption of dedicated
      techniques for catheter delivery and echocardiographic imaging. In experienced
      operators, the potential for prosthetic leaflet impingement is the predominant
      limitation of the procedure. These data have implications for physician training
      and performance in complex structural heart disease interventions.

PMID- 24746658
TI  - Unintentional "ventriculo-phlebo-myo-pericardiography".

PMID- 24746659
TI  - Spectroscopic studies of alpha tocopherol interaction with a model liposome and
      its influence on oxidation dynamics.
AB  - The influence of alpha-tocopherol on the surface conformation of liposome, as a
      model component of lipoproteins, and its role in oxidation process were studied.
      FT-IR spectra from suspensions of neat liposome, mixtures of liposome and alpha
      tocopherol and liposome with incorporated alpha-tocopherol were analyzed. When
      alpha-tocopherol was incorporated into liposome, intensities of some bands were
      decreased or increased in comparison with the spectra of liposome and alpha
      tocopherol mixture. These changes reflect the different localization of alpha
      tocopherol in two types of liposome suspensions. The oxidation of liposome
      suspensions was initiated by addition of cupric ions. After prolonged oxidation,
      the differences in FT-IR spectra of oxidized samples were recorded. Differences
      were observed in comparison with spectra of native and oxidized liposomes were
      analyzed. The rate of oxidation was measured by EPR oximetry. Oxidation was
      generally very slow, but faster in liposome without alpha-tocopherol, indicating
      the protective role of alpha-tocopherol against liposome oxidation. On the other
      hand, liposome suspensions with EDTA in the buffer were not oxidized at all,
      while those with alpha-tocopherol and liposome mixture were only slightly
      oxidized. In this case the consumption of oxygen was the result of liposome
      oxidation supported by alpha-tocopherol. These results reflect the ambivalent
      role of alpha-tocopherol in liposome oxidation, similarly to findings in studies
      of lipoprotein oxidation. 

PMID- 24746660
TI  - Breakfast skipping is associated with cyberbullying and school bullying
      victimization. A school-based cross-sectional study.
AB  - Breakfast skipping is a health concern that has well-known negative consequences
      physically and psychologically. It is therefore important to understand why
      children skip breakfast. The purpose of this study was to establish whether the
      experience of bullying and cyberbullying impacts upon breakfast skipping and to
      further evaluate whether the inability for youths to cope with bullying
      victimization affects their mental health (depression), and in turn predicts
      breakfast skipping. Data were obtained from the Eastern Ontario 2011 Youth Risk
      Behaviour Survey, a cross-sectional regional school-based survey of middle and
      high school students (11-20 years old) across the five counties of Eastern
      Ontario, Canada (N = 3035). Self-reported data about children's experiences of
      bullying victimization, breakfast eating habits, socio-economical status,
      depression, and other risk behaviours were analysed. Approximately half of the
      participants (50.4%) reported not eating breakfast on a regular basis: 26.3% and
      24.1% reported often (usually eat breakfast three times or more per week) and
      frequent (usually eat breakfast twice a week or less) breakfast skipping
      behaviour, respectively. Victims of both cyberbullying and school bullying
      presented greater likelihood of often (adjusted relative risk ratio (RR) = 1.55;
      95% confidence interval (CI) = 1.17-2.06) and frequent (RR = 1.97; 95% CI = 1.28
      3.03) breakfast skipping. Mediation analysis further showed that depression fully
      mediated the relationship between school bullying victimization and frequent
      breakfast skipping. Moreover, depression partially mediated the associations
      between both cyberbullying and school bullying with frequent breakfast skipping.
      These findings highlight the potential interrelationships between cyberbullying,
      school bullying and depression in predicting unhealthy breakfast skipping
      behaviour in children.

PMID- 24746661
TI  - Health-related quality of life outcomes after robot-assisted and open radical
      cystectomy using a validated bladder-specific instrument: a multi-institutional
      study.
AB  - OBJECTIVE: To evaluate health-related quality of life (HRQL) using validated
      bladder-specific Bladder Cancer Index (BCI) and European Organization for
      Research and Treatment of Cancer Body Image scale (BIS) between open radical
      cystectomy (ORC) and robot-assisted radical cystectomy (RARC). METHODS: This was
      a retrospective case series of all patients who underwent radical cystectomy.
      Patients were grouped based on surgical approach (open vs robot assisted) and
      diversion technique (extracorporeal vs intracorporeal). Patients completed BCI
      and BIS preoperatively and at standardized postoperative intervals (at least 2).
      The primary exposure variable was surgical approach. The primary outcome measure
      was difference in interval and baseline BCI and BIS scores in each group. The
      Fisher exact, Wilcoxon rank-sum, and Kruskal-Wallis tests were used for
      comparisons. RESULTS: Eighty-two and 100 patients underwent RARC and ORC,
      respectively. Compared with RARC, more patients undergoing ORC had an American
      Society of Anesthesiology score>=3 (66% vs 45.1% RARC; P=.007) and shorter median
      operative time (350 vs 380 minutes; P=.009). Baseline urinary, bowel, sexual
      function, and body image were not different between both the groups (P=1.0).
      Longitudinal postoperative analysis revealed better sexual function in ORC group
      (P=.047), with no significant differences between both the groups in the other 3
      domains (P=.11, .58, and .93). Comparisons regarding diversion techniques showed
      similar findings in baseline and postoperative HRQL data, with no significant
      differences in the HRQL and body image domains. CONCLUSION: RARC has comparable
      HRQL outcomes to ORC using validated BCI and BIS. The diversion technique used
      does not seem to affect patients' quality of life.

PMID- 24746662
TI  - Detection of uric acid stones in the ureter using low- and conventional-dose
      computed tomography.
AB  - OBJECTIVE: To determine the ability of low- and conventional-dose computed
      tomography (CT) in identification of uric acid stones, which are of lower density
      than calcium oxalate stones. MATERIALS AND METHODS: Uric acid stones (3, 5, and 7
      mm) were randomly placed in human cadaveric ureters and scanned using
      conventional 140-mAs and low-dose 70-, 50-, 30-, 15-, 7.5-, and 5-mAs settings. A
      single-blinded radiologist reviewed a total of 523 scanned stone images.
      Sensitivity and specificity were compared among different settings and stone
      sizes. RESULTS: Imaging using 140-, 70-, 50-, 30-, 15-, 7.5-, and 5-mAs settings
      resulted in 97%, 97%, 96%, 93%, 83%, 83%, and 69% sensitivity and 92%, 92%, 91%,
      89%, 88%, 91%, and 94% specificity, respectively. There was a significant
      difference in sensitivity between 140 mAs and 15, 7.5, and 5 mAs (P = .011, P =
      .011, and P <.001, respectively). Sensitivity for 3-, 5-, and 7-mm stones was
      83%, 90%, and 93%, respectively. At <= 15 mAs, 3-mm stones had a higher rate of
      false negatives (P <.001). CONCLUSION: Both low- and conventional-dose CTs
      demonstrate excellent sensitivity and specificity for the detection of ureteral
      uric acid stones. However, low-dose CT at <= 15 mAs resulted in reduced detection
      of uric acid stones.

PMID- 24746663
TI  - Implications of a 5-liter urinary bladder: inferior vena cava syndrome leading to
      bilateral pulmonary artery emboli.
AB  - Compression of the inferior vena cava by the distended urinary bladder is rare
      but is usually found in the presence of lower extremity edema. Here, we present
      the case of a 68-year-old man found to have multiple pulmonary emboli as the
      first manifestation of inferior vena cava compression from a distended urinary
      bladder 5 L in capacity. 

PMID- 24746664
TI  - Time to start measuring surgical skill? Commentary on: Surgical skill and
      complication rates after bariatric surgery.

PMID- 24746665
TI  - Biochemical recurrence-free survival after robotic-assisted laparoscopic vs open
      radical prostatectomy for intermediate- and high-risk prostate cancer.
AB  - OBJECTIVE: To compare biochemical recurrence (BCR)-free survival and predictors
      of BCR in intermediate-risk (IR) and high-risk (HR) patients undergoing robotic
      assisted laparoscopic prostatectomy (RALP) vs open radical prostatectomy (ORP).
      MATERIALS AND METHODS: We conducted a retrospective study on 1336 men with
      D'Amico IR or HR prostate cancer who underwent RALP or ORP between 2003 and 2009.
      Exclusion criteria were use of neoadjuvant therapy, <6 months of follow-up, and
      insufficient clinicopathologic data. We compared demographic, clinical, and
      pathologic variables between groups. Kaplan-Meier analysis was performed to
      compare the 5-year BCR-free survival between groups. Multivariate models were
      developed to determine whether surgical approach influences BCR. RESULTS: A total
      of 979 IR and HR patients (237 ORP and 742 RALP patients) met inclusion criteria.
      Median follow-up was shorter for RALP (43 vs 63 months; P<.001). ORP patients had
      a higher median prostate-specific antigen level (7.9 vs 6.7 ng/mL; P<.002),
      significantly more Gleason sum 8-10 tumors, and more adverse pathologic features
      overall. There was no difference in positive surgical margins between groups.
      Pathologic features including extraprostatic extension, seminal vesicle
      involvement, lymph node involvement, pathologic Gleason sum, and positive
      surgical margin were significant independent predictors of BCR in multivariate
      analysis. Surgical approach (RALP vs ORP) did not predict BCR when controlling
      for other known predictors of BCR. CONCLUSION: Among IR and HR prostate cancer
      patients, the oncologic outcomes are similar between RALP and ORP. Not
      surprisingly, adverse pathologic features are harbingers of BCR.

PMID- 24746666
TI  - Detecting positive surgical margins using single optical fiber probe during
      radical prostatectomy: a pilot study.
AB  - OBJECTIVE: To investigate for the potential of detection of positive surgical
      margins by the elastic light single-scattering spectroscopy (ELSSS) system with a
      single optical fiber probe during radical prostatectomy. MATERIALS AND METHODS:
      ELSSS spectra in the 450- to 750-nm wavelength regions were obtained from a total
      of 31 benign tissue samples and 14 malignant tissue samples from 18 patients. The
      ELSSS spectral data were assessed by comparing these against the "gold standard"
      histopathology results. Data were analyzed using principal component analysis ,
      followed by linear discriminant analysis. Receiver operating characteristic curve
      analysis was used for differentiating performance. RESULTS: Classification based
      on the discriminant score provided a sensitivity of 86% and a specificity of 97%,
      in differentiating benign from malignant surgical margins of prostate tissues,
      with a positive predictive value of 0.92, a negative predictive value of 0.94,
      and the area under the receiver operating characteristic curve of 0.87.
      CONCLUSION: The ELSSS system can accurately distinguish between benign and
      malignant surgical margins of prostate tissues with a high positive predictive
      value and negative predictive value. It is a promising technique, and it may be a
      valuable new tool for determining positive surgical margins during radical
      prostatectomy.

PMID- 24746667
TI  - Olfactory bulb volume and olfactory function after radiotherapy in patients with
      nasopharyngeal cancer.
AB  - OBJECTIVE: Radiotherapy is the primary method of treatment for nasopharyngeal
      cancer (NPC) and many side effects were reported in patients receiving radiation
      to this area. This study was conducted to evaluate the long-term effects of
      radiotherapy following NPC on olfactory bulb (OB) volume and olfactory function.
      METHODS: Twenty-four patients with NPC who received radiotherapy at least 12
      months ago were recruited. Fourteen healthy subjects with similar demographical
      characteristics were recruited as the healthy control group. All volunteers were
      subjected to a nasoendoscopical examination, and abnormalities that could
      potentially cause olfactory dysfunction were the exclusion criteria from the
      study. An experienced radiologist segmented the MRI coronal, axial and sagittal
      slices manually for three-dimensional OB volume measurement in a blinded manner.
      Olfactory function was assessed using the Connecticut Chemosensory Clinical
      Research Center (CCCRC) test, and average score (0: worst, 7: best) was
      calculated as the total CCCRC olfactory score. RESULTS: The mean CCCRC score was
      5.5 +/- 1.1 for the nasopharyngeal cancer patients, whereas the mean score of
      healthy control group was 6.4 +/- 0.4. There was a significant difference in the
      olfactory scores (p=0.003). The mean OB volume in the NPC group was 46.7 +/-
      12.1mm(3). Among the patients with NPC, the cisplatin receiving group had a mean
      OB volume of 47.2mm(3), whereas the cisplatin+docetaxel receiving group had a
      mean OB volume of 46.5mm(3), and they were similar. The MRI measurement of the
      healthy control group was 58.6 +/- 13.8mm(3). The OB volumes of the healthy
      control group were significantly higher (p<0.05). CONCLUSION: Radiotherapy
      following nasopharyngeal cancer results in a diminished OB volume and
      deteriorated olfactory function. Chemosensory olfactory dysfunction might be a
      contributing factor to lack of appetite, cancer cachexia and consequent lowered
      quality of life in NPC patients.

PMID- 24746668
TI  - Risk factors for acute pulmonary edema after adenotonsillectomy in children.
AB  - OBJECTIVE: Adenotonsillectomy is a common surgical procedure in children. Acute
      pulmonary edema after this procedure is a rare complication but may be fatal. The
      factors associated with pulmonary edema after adenotonsillectomy were studied.
      METHODS: All consecutive patients with an age of less than 15 years who underwent
      adenotonsillectomy at Chiang Mai University Hospital were enrolled. The study
      period was from January 2004 to December 2008. Clinical factors were
      retrospectively retrieved from medical records. Factors associated with acute
      pulmonary edema after adenotonsillectomy were computed using multiple logistic
      regression analysis. RESULTS: There were 216 patients who underwent
      adenotonsillectomy due to airway obstruction during the study period. Five
      patients were excluded due to incomplete data. Of those included, 129 patients
      (61.1%) were male with mean age of 6.6 (SD 3.2) years. Four significant factors
      associated with the development of post-operative pulmonary edema after the
      adenotonsillectomy were procedure, age, obesity, and pulmonary hypertension.
      CONCLUSION: Factors associated with acute pulmonary edema after
      adenotonsillectomy in children were adenotonsillectomy procedure, young age,
      obesity, or having pulmonary hypertension. Clinicians should be aware of these
      risk factors while performing adenotonsillectomy in children.

PMID- 24746670
TI  - Evolving Hox activity profiles govern diversity in locomotor systems.
AB  - The emergence of limb-driven locomotor behaviors was a key event in the evolution
      of vertebrates and fostered the transition from aquatic to terrestrial life. We
      show that the generation of limb-projecting lateral motor column (LMC) neurons in
      mice relies on a transcriptional autoregulatory module initiated via transient
      activity of multiple genes within the HoxA and HoxC clusters. Repression of this
      module at thoracic levels restricts expression of LMC determinants, thus
      dictating LMC position relative to the limbs. This suppression is mediated by a
      key regulatory domain that is specifically found in the Hoxc9 proteins of
      appendage-bearing vertebrates. The profile of Hoxc9 expression inversely
      correlates with LMC position in land vertebrates and likely accounts for the
      absence of LMC neurons in limbless species such as snakes. Thus, modulation of
      both Hoxc9 protein function and Hoxc9 gene expression likely contributed to
      evolutionary transitions between undulatory and ambulatory motor circuit
      connectivity programs. 

PMID- 24746671
TI  - Acetaldehyde targets superoxide dismutase 2 in liver cancer cells inducing
      transient enzyme impairment and a rapid transcriptional recovery.
AB  - Alcohol is undoubtedly, the main toxic agent that people consume by recreation
      and the abuse is associated with liver damage, mainly by the overproduction of
      reactive oxygen species and the toxic effects of its first metabolite
      acetaldehyde. It is known that acetaldehyde targets mitochondria inducing redox
      imbalance and oxidative stress. Mitochondrial superoxide dismutase transforms
      superoxide radical into hydrogen peroxide, which in addition, is transformed in
      water by other enzymes. In the present study we demonstrate that acetaldehyde
      transiently impairs SOD2 activity in HepG2 cells, the decrease in the enzyme
      activity was associated to a reduction in the protein content, which was rapidly
      recovered, to basal values, by synthesis de novo in a mechanism mediated by NF
      kappaB and PKC. The SOD2 impairment was not associated with adduct formation. The
      recovery on SOD2 activity in HepG2 cells can represent survival advantage for
      cancer cells, the results shown that SOD2 could be considered a therapeutic
      target in liver cancer. 

PMID- 24746669
TI  - Cyclin B1/Cdk1 coordinates mitochondrial respiration for cell-cycle G2/M
      progression.
AB  - A substantial amount of mitochondrial energy is required for cell-cycle
      progression. The mechanisms underlying the coordination of the mitochondrial
      respiration with cell-cycle progression, especially the G2/M transition, remain
      to be elucidated. Here, we show that a fraction of cyclin B1/Cdk1 proteins
      localizes to the matrix of mitochondria and phosphorylates a cluster of
      mitochondrial proteins, including the complex I (CI) subunits in the respiratory
      chain. Cyclin B1/Cdk1-mediated CI phosphorylation enhances CI activity, whereas
      deficiency of such phosphorylation in each of the relevant CI subunits results in
      impairment of CI function. Mitochondria-targeted cyclin B1/Cdk1 increases
      mitochondrial respiration with enhanced oxygen consumption and ATP generation,
      which provides cells with efficient bioenergy for G2/M transition and shortens
      overall cell-cycle time. Thus, cyclin B1/Cdk1-mediated phosphorylation of
      mitochondrial substrates allows cells to sense and respond to increased energy
      demand for G2/M transition and, subsequently, to upregulate mitochondrial
      respiration for successful cell-cycle progression. 

PMID- 24746672
TI  - Implementing toileting trials in nursing homes: evaluation of a dissemination
      strategy.
AB  - OBJECTIVES: This study sought to improve incontinence care in nursing homes (NHs)
      by administering and evaluating a webinar course that provided extended
      instruction to help NHs implement toileting trials in accordance with recommended
      procedures. Of particular interest was: 1) whether the course design would prompt
      NH staffs to implement the recommended protocol, and 2) whether participants
      preferred this course design to other models. DESIGN: The study collected
      descriptive evaluation data. SETTING: The setting was comprised of seven NHs.
      PARTICIPANTS: Participants were staff members, typically nurses, from enrolled
      NHs who attended at least three of the six webinars that comprised the course.
      MEASURES: Data was collected using a course evaluation and implementation survey.
      RESULTS: Staff in the participating nursing homes attended an average of 4.85
      webinars, with an average of nine staff members attending each webinar (range: 3
      20). Twelve of 16 responding participants said they preferred the webinar course
      to other course designs. All respondents said they would recommend the course and
      take a similar course again. All facilities submitted some evidence that staff
      providers had completed implementation assignments. Most facilities reported
      plans to sustain use of the recommended protocol. CONCLUSION: This study found
      limited evidence that the webinar course prompts NHs to implement a recommended
      toileting trial protocol and is preferred to other training program designs.

PMID- 24746673
TI  - Face-name memory in Alzheimer's disease.
AB  - Alzheimer's disease (AD) affects face-name memory, the ability to recognize faces
      and recall names. Remembering face and name requires a sophisticated cognitive
      process because of the complexity and similarity among faces and also because of
      their arbitrary association with names. Assessments of face-name memory can
      measure episodic and semantic memory performance and are useful for early
      detection of AD. Improving face-name memory is possible through cognitive
      interventions targeted to promote procedural memory, which is often preserved
      until the late stage of AD. This article describes a conceptual model, assessment
      tools, and strategies for improving face-name memory in persons with AD. 

PMID- 24746674
TI  - Default mode network hypometabolism in epileptic encephalopathies with CSWS.
AB  - Previous studies investigating cerebral metabolic changes associated with
      continuous spike-waves during sleep (CSWS) compared the metabolism of children
      with CSWS with that of healthy adults, precluding any assessment in brain areas
      showing physiologic age-related metabolic changes. Here, we investigated the
      metabolic and connectivity changes characterizing the acute phase of CSWS
      activity by comparing awake brain metabolism of children with CSWS with that of
      pediatric pseudo-controls. Positron emission tomography using [18F]
      fluorodeoxyglucose (FDG-PET) was performed in 17 awake children with cryptogenic
      CSWS (5 girls, age: 5-11 years). Voxel-based analyses identified significant
      metabolic changes in CSWS patients compared with 18 pediatric pseudo-controls (12
      girls, age: 6-11 years, non-CSWS focal cryptogenic epilepsy with normal FDG-PET).
      CSWS-induced changes in the contribution of brain areas displaying metabolic
      changes to the level of metabolic activity in other brain areas were investigated
      using pathophysiological interaction. Hypermetabolism in perisylvian regions
      bilaterally and hypometabolism in lateral and mesial prefrontal cortex,
      precuneus, posterior cingulate cortex and parahippocampal gyri characterized the
      acute phase of CSWS (p<0.05 FWE). No change in thalamic metabolism was disclosed.
      Altered functional connectivity was found between hyper- and hypometabolic
      regions in CSWS patients compared with pediatric pseudo-controls. This study
      demonstrates hypometabolism in key nodes of the default mode network (DMN) in
      awake patients with CSWS, in relation with a possible phenomenon of sustained
      remote inhibition from the epileptic foci. This hypometabolism might account for
      some of the acquired cognitive or behavioral features of CSWS epileptic
      encephalopathies. This study failed to find any evidence of thalamic metabolic
      changes, which supports the primary involvement of the cortex in CSWS genesis. 

PMID- 24746675
TI  - Human somatic cell nuclear transfer using adult cells.
AB  - Derivation of patient-specific human pluripotent stem cells via somatic cell
      nuclear transfer (SCNT) has the potential for applications in a range of
      therapeutic contexts. However, successful SCNT with human cells has proved
      challenging to achieve, and thus far has only been reported with fetal or infant
      somatic cells. In this study, we describe the application of a recently developed
      methodology for the generation of human ESCs via SCNT using dermal fibroblasts
      from 35- and 75-year-old males. Our study therefore demonstrates the
      applicability of SCNT for adult human cells and supports further investigation of
      SCNT as a strategy for regenerative medicine. 

PMID- 24746676
TI  - Extrapituitary growth hormone and growth?
AB  - While growth hormone (GH) is obligatory for postnatal growth, it is not required
      for a number of growth-without-GH syndromes, such as early embryonic or fetal
      growth. Instead, these syndromes are thought to be dependent upon local growth
      factors, rather than pituitary GH. The GH gene is, however, also expressed in
      many extrapituitary tissues, particularly during early development and
      extrapituitary GH may be one of the local growth factors responsible for
      embryonic or fetal growth. Moreover, as the expression of the GH receptor (GHR)
      gene mirrors that of GH in extrapituitary tissues the actions of GH in early
      development are likely to be mediated by local autocrine or paracrine mechanisms,
      especially as extrapituitary GH expression occurs prior to the ontogeny of
      pituitary somatotrophs or the appearance of GH in the circulation. The
      extrapituitary expression of pituitary somatotrophs or the appearance of GH in
      the circulation. The extrapituitary expression of GH in embryos has also been
      shown to be of functional relevance in a number of species, since the
      immunoneutralization of endogenous GH or the blockade of GH production is
      accompanied by growth impairment or cellular apoptosis. The extrapituitary
      expression of the GH gene also persists in some central and peripheral tissues
      postnatally, which may reflect its continued functional importance and
      physiological or pathophysiological significance. The expression and functional
      relevance of extrapituitary GH, particularly during embryonic growth, is the
      focus of this brief review. 

PMID- 24746677
TI  - Dopamine and prolactin involvement in the maternal care of chicks in the native
      Thai hen (Gallus domesticus).
AB  - The dopaminergic (DAergic) system plays a pivotal role in incubation behavior via
      the regulation of prolactin (PRL) secretion in birds, however the role of the
      DA/PRL system in rearing behavior is poorly understood. The objective of this
      study was to investigate the relationship between the DA/PRL system and rearing
      behavior in a gallinaceous bird, the native Thai chicken. Incubating native Thai
      hens were divided into two groups. In the first group, hens were allowed to care
      for their chicks (rearing hens; R). In the second group, hens were deprived of
      their chicks immediately after hatching (non-rearing hens; NR). In both groups,
      blood samples and brain sections were collected at different time points after
      the chicks hatched (days 4, 7, 10, 14, 17, 21, 24, and 28; 6 hens/time
      point/group). In this study, tyrosine hydroxylase (TH) was used as a marker for
      DAergic neurons. The numbers of TH-immunoreactive (-ir) neurons in the nucleus
      intramedialis (nI) and in the nucleus mamillaris lateralis (ML), which regulate
      the vasoactive intestinal peptide (VIP)/PRL system, were determined in R and NR
      hens utilizing immunohistochemical techniques. Plasma PRL levels were determined
      by enzyme-linked immunosorbent assays. The results revealed that both the number
      of TH-ir neurons in the nI and the plasma PRL levels were significantly higher in
      the R hens compared with the NR hens during the first 14 days of chick rearing
      (P<0.05). However, there was no significant change in the DAergic activity in the
      ML in either the R or NR groups throughout the 28-day rearing periods. These
      results suggest that the DA/PRL system is involved in early rearing behavior. The
      additional decline in DAergic activity and plasma PRL levels during the
      disruption of rearing behavior further supports their involvement in rearing
      behavior in this equatorial precocial species.

PMID- 24746678
TI  - Masculine boys, feminine girls, and cancer risk behaviors: an 11-year
      longitudinal study.
AB  - OBJECTIVE: Cancer risk behaviors often begin in adolescence and persist through
      adulthood. Tobacco use, indoor tanning, and physical inactivity are highly
      prevalent, socially patterned cancer risk behaviors, and their prevalence differs
      strongly by sex. It is therefore possible that these behaviors also differ by
      gender expression within the sexes due to social patterning. METHODS: We examined
      whether five cancer risk behaviors differed by childhood gender expression within
      the sexes and whether patterns of media engagement (e.g., magazine readership and
      trying to look like media personalities) explained possible differences, in a
      U.S. population-based cohort (N = 9,435). RESULTS: The most feminine girls had
      higher prevalence of indoor tanning (prevalence risk ratio [pRR] = 1.32, 95%
      confidence interval [CI] = 1.23-1.42) and physical inactivity (pRR = 1.16, 95% CI
      = 1.01-1.34) and lower prevalence of worse smoking trajectory (prevalence odds
      ratio = .75, 95% CI = .65-.88) and smoking cigars (pRR = .61, 95% CI = .47-.79)
      compared with least feminine girls. Media engagement accounted for part of the
      higher prevalence of indoor tanning. The most masculine boys were more likely to
      chew tobacco (pRR = 1.78, 95% CI = 1.14-2.79) and smoke cigars (pRR = 1.55, 95%
      CI = 1.17-2.06) but less likely to follow a worse smoking trajectory (prevalence
      odds ratio = .69, 95% CI = .55-.87) and be physically inactive (pRR = .54, 95% CI
      = .43-.69) compared with least masculine boys. CONCLUSIONS: We found some strong
      differences in patterns of cancer risk behaviors by gender expression within the
      sexes. Prevention efforts that challenge the "masculinity" of smoking cigarettes
      and cigars and chewing tobacco and the "femininity" of indoor tanning to reduce
      their appeal to adolescents should be explored.

PMID- 24746679
TI  - Adolescent neck and shoulder pain--the association with depression, physical
      activity, screen-based activities, and use of health care services.
AB  - PURPOSE: Neck and shoulder pain is frequent in adolescents, and multiple factors
      seem to affect the risk of such symptoms. We aimed to investigate the prevalence
      of neck and shoulder pain in Norwegian adolescence and to examine whether
      behavioral and emotional factors were associated with the risk of neck and
      shoulder pain. Finally we aimed to investigate whether neck and shoulder pain was
      related to the use of health services. METHOD: Data from the population-based
      study ung@hordaland were used. Participants were asked how often during the last
      6 months they had experienced neck and shoulder pain. The association between
      frequent neck and shoulder pain and physical activity, symptoms of depression,
      and screen-based activities was evaluated using logistic regression analyses
      stratified by gender. The relative risk of visiting health services when
      reporting neck and shoulder pain was calculated using multiple logistic
      regression analyses. RESULTS: Frequent neck and shoulder pain was reported by
      20.0% (1,797 of the total 8,990) and more often by girls than boys (p < .001). A
      high score of depressive symptoms was the strongest risk factor for neck and
      shoulder pain in both boys and girls (odds ratio = 6.14 [95% confidence interval
      4.48-8.42] and odds ratio = 3.10 [95% confidence interval 2.63-3.67],
      respectively). Frequent screen-based activities slightly increased the risk while
      physical activity was protective. Individuals reporting neck and shoulder pain
      more often visited their general practitioner (47.1% vs. 31.8%) and school health
      services (24.6% vs. 13.5%). CONCLUSION: Frequent neck and shoulder pain was
      reported in 20% of Norwegian adolescents. Symptoms of depression and screen-based
      activities increased the risk of neck and shoulder pain while physical activity
      was protective. Individuals reporting neck and shoulder pain visited health
      services more frequently than others.

PMID- 24746680
TI  - The Maillard reaction of bisoprolol fumarate with various reducing carbohydrates.
AB  - HPLC analysis of drug products containing bisoprolol fumarate and lactose
      revealed the presence of N-formylbisoprolol, which is a final product of the
      Maillard reaction. Formulations containing secondary amines and reducing
      carbohydrates are prone to the condensation of amine and carbonyl functional
      groups and formation of glycosylamines in pharmaceutically relevant conditions.
      Further rearrangement occurs in the presence of a nucleophile and leads to the
      formation of 1-deoxy-1-amino-2-ketose also known as the Amadori Rearrangement
      Product (ARP). The influence of water content, carbohydrate, and lubricant types
      on the reaction rate was tested. The reaction progress was monitored by HPLC and
      UV-Vis spectrophotometry. The structures of intermediates were confirmed by the
      LC/MS(2) analysis. N-formylbisoprolol - the final reaction product - was
      synthesised and characterised by LC/MS(2), H(1) and C(13) NMR. 

PMID- 24746681
TI  - Genomics of liver transplant injury and regeneration.
AB  - While improved surgical techniques, post-operative care, and immunosuppression
      regimens have reduced morbidity and mortality associated with orthotopic liver
      transplantation (OLT), further improvement of outcomes requires personalized
      treatment and a better understanding of genomic mechanisms involved. Gene
      expression profiles of ischemia/reperfusion (I/R) injury, regeneration, and
      rejection, may suggest mechanisms for development of better predictive tools and
      treatments. The liver is unique in its regenerative potential, recovering lost
      mass and function after injury from ischemia, resection, and rejection. I/R
      injury, an inevitable consequence of perfusion cessation, cold storage, and
      reperfusion, is regulated by the interaction of the immune system, inflammatory
      cytokines, and reduced microcirculatory blood flow in the liver. Rejection, a
      common post-operative complication, is mediated by the recipient's immune system
      through T-cell-dependent responses activating proinflammatory and apoptotic
      pathways. Characterizing distinctive gene expression signatures for these events
      can identify therapies to reduce injury, promote regeneration, and improve
      outcomes. While certain markers of liver injury and regeneration have been
      observed in animals, many of these are unverified in human studies. Further
      investigation of these genomic signatures and mechanisms through new technology
      offers promise, but continues to pose a significant challenge. An overview of the
      current fund of knowledge in this area is reviewed. 

PMID- 24746682
TI  - Altered progesterone concentrations by hormonal manipulations before a fixed-time
      artificial insemination CO-Synch + CIDR program in suckled beef cows.
AB  - We hypothesized that pregnancy outcomes may be improved by inducing luteal
      regression, ovulation, or both (i.e., altering progesterone status) before
      initiating a timed-artificial insemination (TAI) program in suckled beef cows.
      This hypothesis was tested in two experiments in which cows were treated with
      either PGF2alpha (PG) or PG + GnRH before initiating a TAI program to increase
      the proportion of cows starting the program in a theoretical marginal (<1 ng/mL;
      experiment 1) or elevated (>=1 ng/mL; experiment 2) progesterone environment,
      respectively. The control was a standard CO-Synch + controlled internal drug
      release (CIDR) program employed in suckled beef cows (100 MUg GnRH
      intramuscularly [IM] [GnRH-1] and insertion of a progesterone-impregnated
      intravaginal CIDR insert on study Day -10, 25 mg PG and CIDR insert removal on
      study Day -3, and 100 MUg GnRH IM [GnRH-2] and TAI on study Day 0). In both
      experiments, blood was collected before each injection for later progesterone
      analyses. In experiment 1, cows at nine locations (n = 1537) were assigned to
      either: (1) control or (2) PrePG (same as control with a PG injection on study
      Day -13). The PrePG cows had larger (P < 0.05) follicles on study Day -10 and
      more (P < 0.05) ovulated after GnRH-1 compared with control cows (60.6% vs.
      36.5%), but pregnancy per TAI was not altered (55.5% vs. 52.2%, respectively). In
      experiment 2, cows (n = 803) at four locations were assigned to: (1) control or
      (2) PrePGG (same as control with PG injection on study Day -20 and GnRH injection
      on study Day -17). Although pregnancy per TAI did not differ between control and
      PrePGG cows (44.0% vs. 44.4%, respectively), cows with body condition score
      greater than 5.0 or 77 or more days postpartum at TAI were more (P < 0.05) likely
      to become pregnant than thinner cows or those with fewer days postpartum.
      Presynchronized cows in both experiments were more (P < 0.05) likely than
      controls to have luteolysis after initial PG injections and reduced (P < 0.05)
      serum progesterone; moreover, treatments altered the proportion of cows and
      pregnancy per TAI of cows in various progesterone categories before the onset of
      the TAI protocol. In combined data from both experiments, cows classified as
      anestrous before the study but with elevated progesterone on Day -10 had
      increased (P < 0.05) pregnancy outcomes compared with anestrous cows with low
      progesterone concentrations. Progesterone concentration had no effect on
      pregnancy outcome of cycling cows. In summary, luteal regression and ovulation
      were enhanced and progesterone concentrations were altered by presynchronization
      treatments before the 7-day CO-Synch + CIDR program, but pregnancy per TAI was
      not improved. 

PMID- 24746683
TI  - Treatment of pediatric chronic viral hepatitis B and C.

PMID- 24746684
TI  - Cholestasis in the newborn and infant.
AB  - Neonatal cholestasis occurs in approximately 1 in 2500 term infants, the most
      common underlying disease being biliary atresia, viral infections and alpha1
      antitrypsin deficiency. The incidence of cholestasis is much higher in extremely
      premature newborns. The etiology of biliary atresia remains unclear, which in
      turn makes the search for additional treatments to surgery challenging. Reliable
      non-invasive tools to differentiate biliary atresia from other forms of neonatal
      cholestasis need to be further investigated. Despite important findings in the
      last decades, the pathogenesis of cholestatic liver disease in alpha1-antitrypsin
      deficiency remains to be clarified. Any such explanation would also need to
      explain why only a minority of individuals with PiZZ phenotype develop liver
      disease. For other genetic diseases causing neonatal cholestasis, such as
      Alagille's syndrome and progressive familial intrahepatic cholestasis the
      breakthrough within the field of molecular biology has definitely deepened our
      understanding of both etiology and pathogenesis. However, the correlation between
      genotype and phenotype is rarely obvious and for several patients with the
      seemingly correct phenotype no known genetic mutation is detected. A stepwise
      approach to the management of cholestasis in the newborn and infant is suggested,
      where percutaneous liver biopsy is of value to select patients with suspected
      biliary atresia for laparotomy. 

PMID- 24746685
TI  - Gender differences in brain activity and the relationship between brain activity
      and differences in prevalence rates between male and female major depressive
      disorder patients: a resting-state fMRI study.
AB  - OBJECTIVE: We examined the gender-difference effect on abnormal spontaneous
      neuronal activity of male and female major depressive disorder (MDD) patients
      using the amplitude of low-frequency fluctuation (ALFF) and the further clarified
      the relationship between the abnormal ALFF and differences in MDD prevalence
      rates between male and female patients. METHODS: Fourteen male MDD patients, 13
      female MDD patients and 15 male and 15 female well matched healthy controls (HCs)
      completed this study. The ALFF approach was used, and Pearson correlation was
      conducted to observe a possible clinical relevance. RESULTS: There were
      widespread differences in ALFF values between female and male MDD patients,
      including some important parts of the frontoparietal network, auditory network,
      attention network and cerebellum network. In female MDD patients, there was a
      positive correlation between average ALFF values of the left postcentral gyrus
      and the severity of weight loss symptom. CONCLUSIONS: The gender-difference
      effect leading to abnormal brain activity is an important underlying
      pathomechanism for different somatic symptoms in MDD patients of different
      genders and is likely suggestive of higher MDD prevalence rates in females.
      SIGNIFICANCE: The abnormal ALFF resulting from the gender-difference effect might
      improve our understanding of the differences in prevalence rates between male and
      female MDD patients from another perspective.

PMID- 24746686
TI  - Changes in diffusion tensor tractographic findings associated with constraint
      induced movement therapy in young children with cerebral palsy.
AB  - OBJECTIVE: The objective of the study was to determine whether constraint-induced
      movement therapy (CIMT) could lead to changes in diffusion tensor tractography
      (DTT) associated with clinical improvement in young children with unilateral
      cerebral palsy (CP). METHODS: A standardized pediatric CIMT protocol (4weeks,
      120h of constraint) was used on 10 children with unilateral CP who were younger
      than 5years. DTT was performed in five participants before and after the
      intervention. Clinical outcome was measured by using the Pediatric Motor Activity
      Log (PMAL), Quality of Upper Extremity Skills Test (QUEST), and self-care domain
      of the Pediatric Evaluation of Disability Inventory. RESULTS: In two patients,
      the affected corticospinal tract (CST) visible on pretreatment DTT became more
      prominent on posttreatment DTT. In one patient, the affected CST was not visible
      on pretreatment DTT, but was visible on posttreatment DTT. All the clinical
      outcomes significantly improved in the CIMT group compared with the control
      group. Changes in the PMAL how often scale (PMAL-HO) score significantly differed
      between the CIMT and control groups. CONCLUSIONS: Changes in the properties of
      the affected CST on DTT were accompanied with improved arm function after CIMT in
      the children with CP. SIGNIFICANCE: CIMT might lead to CST reorganization in
      young children with CP.

PMID- 24746687
TI  - Crystal structure of FtsA from Staphylococcus aureus.
AB  - The bacterial cell-division protein FtsA anchors FtsZ to the cytoplasmic
      membrane. But how FtsA and FtsZ interact during membrane division remains
      obscure. We have solved 2.2 A resolution crystal structure for FtsA from
      Staphylococcus aureus. In the crystals, SaFtsA molecules within the dimer units
      are twisted, in contrast to the straight filament of FtsA from Thermotoga
      maritima, and the half of S12-S13 hairpin regions are disordered. We confirmed
      that SaFtsZ and SaFtsA associate in vitro, and found that SaFtsZ GTPase activity
      is enhanced by interaction with SaFtsA.

PMID- 24746688
TI  - Beyond genetics. Influence of dietary factors and gut microbiota on type 1
      diabetes.
AB  - Type 1 diabetes (T1D) is an autoimmune disease ultimately leading to destruction
      of insulin secreting beta-cells in the pancreas. Genetic susceptibility plays an
      important role in T1D etiology, but even mono-zygotic twins only have a
      concordance rate of around 50%, underlining that other factors than purely
      genetic are involved in disease development. Here we review the influence of
      dietary and environmental factors on T1D development in humans as well as animal
      models. Even though data are still inconclusive, there are strong indications
      that gut microbiota dysbiosis plays an important role in T1D development and
      evidence from animal models suggests that gut microbiota manipulation might prove
      valuable in future prevention of T1D in genetically susceptible individuals. 

PMID- 24746689
TI  - Microbial view of central nervous system autoimmunity.
AB  - Not much is known about the initial events leading to the development of the
      central nervous system (CNS)-specific autoimmune disorder Multiple Sclerosis
      (MS). Environmental factors are suspected to trigger the pathogenic events in
      people with genetic disease susceptibility. Historically, many infectious
      microbes were linked to MS, but no infection has ever been demonstrated to be the
      cause of the disease. Recent emerging evidence from animal models of MS suggests
      a causal link with resident commensal bacteria. Microbial organisms may trigger
      the activation of CNS-specific, auto-aggressive lymphocytes either through
      molecular mimicry or via bystander activation. In addition, several gut microbial
      metabolites and bacterial products may interact with the immune system to
      modulate CNS autoimmunity. 

PMID- 24746690
TI  - Evaluation of P(L)LA-PEG-P(L)LA as processing aid for biodegradable particles
      from gas saturated solutions (PGSS) process.
AB  - A series of biodegradable P(L)LA-PEG1.5 kDa-P(L)LA copolymers have been
      synthesized and compared as processing aid versus Poloxamer 407 (PEO-PPO-PEO), in
      the formulation of protein encapsulated microparticles, using supercritical
      carbon dioxide (scCO2). Bovine serum albumin (BSA) loaded microcarriers were
      prepared applying the particles from the gas saturated solutions (PGSS) technique
      using scCO2 and thus, avoiding the standard practice of organic solvent
      encapsulation. Four triblock copolymers were synthesized and characterized,
      particularly in terms of thermal properties and behaviour when exposed to scCO2.
      The effects of the inclusion of these copolymers in the formulation of poly(alpha
      hydroxy acids) based microparticles - e.g. poly(D,L-lactic-co-glycolic acid)
      (PLGA) and poly(D,L-lactide) (PLA) - were analysed in terms of yield, particle
      size, morphology and drug release. The use of P(L)LA-PEG1.5 kDa-P(L)LA triblock
      copolymers were found to increase the yield of the PGSS-based process and to
      decrease the size of the microparticles produced, in comparison with the
      formulation containing the Poloxamer 407. Moreover the microparticles formulated
      with the triblock copolymers possessing the higher hydrophobic character were
      able to maintain a controlled drug release profile.

PMID- 24746692
TI  - 'Formulating better medicines for children' - the leap forward.

PMID- 24746691
TI  - Transdermal delivery of the in situ hydrogels of curcumin and its inclusion
      complexes of hydroxypropyl-beta-cyclodextrin for melanoma treatment.
AB  - Curcumin (Cur) is a hydrophobic polyphenol with diverse pharmacological effects,
      especially for cancer treatment. However, its weak water solubility and stability
      was the major obstacle for the formulation research of Cur. The complexation of
      Cur and hydroxypropyl-beta-cyclodextrin (HP-beta-CD) was done by grinding. The
      increasing solubility of Cur was achieved due to complexation and the
      photochemical stability of Cur was improved. The inclusion of Cur could happen
      when two ends of Cur were embedded into the cavity of the HP-beta-CD rings. The
      in situ hydrogels (ISGs) of Cur and its inclusion complexes were prepared using
      poloxamers 407 and 188 as the matrix. The extent of drug's in vitro release from
      the ISGs depended on the dissolution of drugs. Both of the ISGs had transdermal
      effect and cytotoxicity on B16-F10 cells. However, the effects of the ISGs
      containing Cur inclusion complexes were much higher than those of Cur ISGs
      because of the improved Cur solubility in the former. The cytotoxicity of Cur on
      melanoma cells was related to blocking of cellular proliferation in the G2/M
      stage followed by cellular apoptosis. The ISGs of Cur inclusion complexes are a
      promising formulation for melanoma treatment.

PMID- 24746693
TI  - Preparation and evaluation of colon adhesive pellets of 5-aminosalicylic acid.
AB  - Oral modified-release delivery systems, such as bio-adhesive one, enable drug
      delivery to affected regions and minimize the side effects by reducing the
      systemic absorption. Our aim was to develop colon adhesive pellets of 5
      aminosalicylic acid (5-ASA) for the treatment of ulcerative colitis. The core of
      the pellet was formulated from bioadhesive agents, Carbomer 940 and hydroxypropyl
      cellulose (HPC), by extrusion/spheronization method and coated with
      Surelease((r)) as inner layer for waterproof and with Eudragit((r)) S100 as outer
      layer for pH control. The rat model of ulcerative colitis was used to evaluate
      the efficiency of our loaded pellets as a drug carrier. Microcrystalline
      cellulose 101 (PH 301) was found to be the best agent for pellet core. The ratio
      of CP940 to HPC should be kept as (1:1) to achieve high bioadhesion. When the
      amount of Surelease((r)) was from 16% to 20% and of Eudragit((r)) S100 was 28%,
      the dissolution profiles of coated pellets revealed no drug release in the
      artificial gastric fluid (pH 1.0) within 2h and less than 10% was released in
      phosphate buffer (pH 6.0) within 2h whereas complete dissolution was observed in
      colonic fluid of pH 7.4 for 20 h. The animal experiment showed that 5-ASA loaded
      colon adhesive pellets had optimal therapeutic effect. We showed a novel approach
      to prepare effective bioadhesive pellets as colon targeted drug delivery system.

PMID- 24746694
TI  - Synthesis and in vitro localization study of curcumin-loaded SPIONs in a micro
      capillary for simulating a targeted drug delivery system.
AB  - Nano-sized curcumin-loaded super-paramagnetic iron oxide nanoparticles (CUR-OA
      SPIONs) were synthesized chemically by co-precipitation method using oleic acid
      as a stabilizer and Myrj 52 as a surfactant. The synthesized nanoparticles were
      characterized for their shape, size, surface morphology, electrokinetic
      potential, magnetic properties, crystalinity, chemical interactions and thermal
      transitions. The synthesized CUR-OA-SPIONs were spherical, mono-dispersed,
      physically stable and super-paramagnetic in nature. In vitro localization study
      and aggregation dynamics of CUR-OA-SPIONs were studied with a flow of blood
      inside a square glass capillary (500*500 MUm(2) cross section) in the presence of
      an externally applied magnetic field (Ms=1200 mT). This research which is first
      of its kind showed the fluorescent imaging of CUR-OA-SPIONs with respect to time
      to understand the aggregation dynamics of magnetic nanoparticles in a micro
      capillary simulating the case of targeted drug delivery system. The size of the
      aggregation increases with respect to time (t=0(+)s to t=500 s), while no
      significant change in the size of the aggregate was observed after time t=500 s.

PMID- 24746695
TI  - Needs, expectations and public knowledge concerning services outside the medical
      basket: a lesson from Israel.
AB  - Quality of and access to medical care are strongly related to the medical basket,
      the set of services covered under the national health insurance system. Various
      health systems offer institutional solutions to cover services that are not
      included in the basket in rare cases. In Israel, patients whose medical needs are
      not covered under the medical basket may apply to committees for exceptional
      cases which are run by all health funds. The article presents the findings of a
      cross-sectional telephone survey which was conducted to explore the public's
      familiarity with the committees for exceptional cases and their workings,
      eligibility, and reporting of treatment required outside the basket. Almost 25%
      of respondents reported that during the past ten years they or their close
      relatives needed medical care, physical examination, or drugs that were not
      included in the medical basket. The survey demonstrates the public's
      unfamiliarity with the committees and uncertainty as to entitlement of services
      which are out of the basket, as well as a tendency to prefer self payment and
      private insurance. Familiarity with committees is strongly related to education,
      race (nationality) and socio-economic status. The treating physician is the major
      source of information on the committee. In case of a need, preference is given to
      private purchase of drugs/services. 

PMID- 24746696
TI  - A regulatory signaling loop comprising the PGAM5 phosphatase and CK2 controls
      receptor-mediated mitophagy.
AB  - Mitochondrial autophagy, or mitophagy, is a major mechanism involved in
      mitochondrial quality control via selectively removing damaged or unwanted
      mitochondria. Interactions between LC3 and mitophagy receptors such as FUNDC1,
      which harbors an LC3-interacting region (LIR), are essential for this selective
      process. However, how mitochondrial stresses are sensed to activate receptor
      mediated mitophagy remains poorly defined. Here, we identify that the
      mitochondrially localized PGAM5 phosphatase interacts with and dephosphorylates
      FUNDC1 at serine 13 (Ser-13) upon hypoxia or carbonylcyanide p
      trifluoromethoxyphenylhydrazone (FCCP) treatment. Dephosphorylation of FUNDC1
      catalyzed by PGAM5 enhances its interaction with LC3, which is abrogated
      following knockdown of PGAM5 or the introduction of a cell-permeable
      unphosphorylated peptide encompassing the Ser-13 and LIR of FUNDC1. We further
      observed that CK2 phosphorylates FUNDC1 to reverse the effect of PGAM5 in
      mitophagy activation. Our results reveal a mechanistic signaling pathway linking
      mitochondria-damaging signals to the dephosphorylation of FUNDC1 by PGAM5, which
      ultimately induces mitophagy. 

PMID- 24746697
TI  - Fragile X mental retardation protein regulates translation by binding directly to
      the ribosome.
AB  - Fragile X syndrome (FXS) is the most common form of inherited mental retardation,
      and it is caused by loss of function of the fragile X mental retardation protein
      (FMRP). FMRP is an RNA-binding protein that is involved in the translational
      regulation of several neuronal mRNAs. However, the precise mechanism of
      translational inhibition by FMRP is unknown. Here, we show that FMRP inhibits
      translation by binding directly to the L5 protein on the 80S ribosome.
      Furthermore, cryoelectron microscopic reconstruction of the 80S ribosome?FMRP
      complex shows that FMRP binds within the intersubunit space of the ribosome such
      that it would preclude the binding of tRNA and translation elongation factors on
      the ribosome. These findings suggest that FMRP inhibits translation by blocking
      the essential components of the translational machinery from binding to the
      ribosome. 

PMID- 24746698
TI  - VEGF Signals through ATF6 and PERK to promote endothelial cell survival and
      angiogenesis in the absence of ER stress.
AB  - Accumulation of unfolded proteins in the endoplasmic reticulum (ER) initiates
      IRE1alpha, ATF6, and PERK cascades, leading to a transcriptional/translational
      response known as unfolded protein response (UPR). Here we show that VEGF
      activates UPR mediators through a PLCgamma-mediated crosstalk with the mTORC1
      complex without accumulation of unfolded proteins in the ER. Activation of ATF6
      and PERK contributes to the survival effect of VEGF on endothelial cells (ECs) by
      positively regulating mTORC2-mediated phosphorylation of AKT on Ser473, which is
      required for full activity of AKT. Low levels of CHOP allow ECs to evade the
      proapoptotic effect of this UPR product. Depletion of PLCgamma, ATF6, or
      eIF2alpha dramatically inhibited VEGF-induced vascularization in mouse Matrigel
      plugs, suggesting that the ER and the UPR machinery constitute components of the
      VEGF signaling circuit that regulates EC survival and angiogenesis, extending
      their role beyond adaptation to ER stress. 

PMID- 24746699
TI  - TFIIH phosphorylation of the Pol II CTD stimulates mediator dissociation from the
      preinitiation complex and promoter escape.
AB  - The transition between transcriptional initiation and elongation by RNA
      polymerase (Pol) II is associated with phosphorylation of its C-terminal tail
      (CTD). Depletion of Kin28, the TFIIH subunit that phosphorylates the CTD, does
      not affect elongation but causes Pol II occupancy profiles to shift upstream in a
      FACT-independent manner indicative of a defect in promoter escape. Stronger
      defects in promoter escape are linked to stronger effects on preinitiation
      complex formation and transcription, suggesting that impairment in promoter
      escape results in premature dissociation of general factors and Pol II near the
      promoter. Kin28 has a stronger effect on genes whose transcription is dependent
      on SAGA as opposed to TFIID. Strikingly, Kin28 depletion causes a dramatic
      increase in Mediator at the core promoter. These observations suggest that TFIIH
      phosphorylation of the CTD causes Mediator dissociation, thereby permitting rapid
      promoter escape of Pol II from the preinitiation complex. 

PMID- 24746700
TI  - Identification of a BRCA1-mRNA splicing complex required for efficient DNA repair
      and maintenance of genomic stability.
AB  - Mutations within BRCA1 predispose carriers to a high risk of breast and ovarian
      cancers. BRCA1 functions to maintain genomic stability through the assembly of
      multiple protein complexes involved in DNA repair, cell-cycle arrest, and
      transcriptional regulation. Here, we report the identification of a DNA damage
      induced BRCA1 protein complex containing BCLAF1 and other key components of the
      mRNA-splicing machinery. In response to DNA damage, this complex regulates pre
      mRNA splicing of a number of genes involved in DNA damage signaling and repair,
      thereby promoting the stability of these transcripts/proteins. Further, we show
      that abrogation of this complex results in sensitivity to DNA damage, defective
      DNA repair, and genomic instability. Interestingly, mutations in a number of
      proteins found within this complex have been identified in numerous cancer types.
      These data suggest that regulation of splicing by the BRCA1-mRNA splicing complex
      plays an important role in the cellular response to DNA damage. 

PMID- 24746701
TI  - Orbitofrontal cortex volume and intrinsic religiosity in non-clinical psychosis.
AB  - Research indicates that religiosity plays a complex role in mental illness.
      Despite this link, little work has been done to clarify the role of religiosity
      in persons exhibiting non-clinical psychosis (NCP, individuals experiencing
      fleeting psychotic-like symptoms in the absence of a formal psychotic disorder).
      Further, there are no NCP investigations into whether abnormalities exist in
      brain structures that are associated with religiosity. Understanding these
      relationships in NCP is important to clarify the role of religiosity and brain
      structural anomalies in psychosis. Twenty individuals experiencing NCP and twenty
      controls were assessed for intrinsic religiosity (IR; motivation/commitment to
      religious beliefs and/or practices) using a well-validated self-report scale.
      Structural magnetic resonance imaging was used to determine volumes of the
      orbitofrontal cortex (OFC), a critical region that has been associated with
      increased religiosity. Results indicate that IR is elevated in the NCP group, and
      that these individuals exhibit bilateral volume reduction in both the lateral and
      medial OFC. Sample-wide correlations are non-significant, but show notable
      relationships between smaller OFC regions and increased IR. Significant negative
      relationships were found between OFC volume and depressive and negative symptoms.
      Overall, results suggest that brain abnormalities associated with NCP may also
      confer a heightened susceptibility for religiosity. 

PMID- 24746702
TI  - A survey of liquid chromatographic-mass spectrometric analysis of mercapturic
      acid biomarkers in occupational and environmental exposure monitoring.
AB  - High-performance liquid chromatography/mass spectrometry (HPLC/MS) is sensitive
      and specific for targeted quantitative analysis and is readily utilized for small
      molecules from biological matrices. This brief review describes recent selected
      HPLC/MS methods for the determination of urinary mercapturic acids
      (mercapturates) which are useful as biomarkers in characterizing human exposure
      to electrophilic industrial chemicals in occupational and environmental studies.
      Electrophilic compounds owing to their reactivity are used in chemical and
      industrial processes. They are present in industrial emissions, are combustion
      products of fossil fuels, and are components in tobacco smoke. Their presence in
      both the industrial and general environments are of concern for human and
      environmental health. Urinary mercapturates which are the products of metabolic
      detoxification of reactive chemicals provide a non-invasive tool to investigate
      human exposure to electrophilic toxicants. Selected recent mercapturate
      quantification methods are summarized and specific cases are presented. The
      biological formation of mercapturates is introduced and their use as biomarkers
      of metabolic processing of electrophilic compounds is discussed. Also, the use of
      liquid chromatography/tandem mass spectrometry in simultaneous determinations of
      the mercapturates of multiple parent compounds in a single determination is
      considered, as well as future trends and limitations in this area of research. 

PMID- 24746703
TI  - Small GTPase RBJ mediates nuclear entrapment of MEK1/MEK2 in tumor progression.
AB  - Ras-related small GTPases play important roles in cancer. However, the roles of
      RBJ, a representative of the sixth subfamily of Ras-related small GTPases, in
      tumorigenesis and tumor progression remain unknown. Here, we report that RBJ is
      dysregulated in human gastrointestinal cancers and can promote carcinogenesis and
      tumor progression via nuclear entrapment of mitogen-activated
      protein/extracellular signal-regulated kinase (ERK) kinase (MEK)1/MEK2 and
      activation of ERK1/ERK2. Nucleus-localized RBJ interacts with MEK/ERK and
      prolongs the duration of MEK/ERK activation. Rbj deficiency abrogates nuclear
      accumulation of MEK1/MEK2, attenuates ERK1/ERK2 activation, and impairs AOM/DSS
      induced colonic carcinogenesis. Moreover, Rbj knockdown inhibits growth of
      established tumors. Our data suggest that RBJ may be an oncogenic Ras-related
      small GTPase mediating nuclear accumulation of active MEK1/MEK2 in tumor
      progression. 

PMID- 24746704
TI  - Disruption of CRAF-mediated MEK activation is required for effective MEK
      inhibition in KRAS mutant tumors.
AB  - MEK inhibitors are clinically active in BRAF(V600E) melanomas but only marginally
      so in KRAS mutant tumors. Here, we found that MEK inhibitors suppress ERK
      signaling more potently in BRAF(V600E), than in KRAS mutant tumors. To understand
      this, we performed an RNAi screen in a KRAS mutant model and found that CRAF
      knockdown enhanced MEK inhibition. MEK activated by CRAF was less susceptible to
      MEK inhibitors than when activated by BRAF(V600E). MEK inhibitors induced RAF-MEK
      complexes in KRAS mutant models, and disrupting such complexes enhanced
      inhibition of CRAF-dependent ERK signaling. Newer MEK inhibitors target MEK
      catalytic activity and also impair its reactivation by CRAF, either by disrupting
      RAF-MEK complexes or by interacting with Ser 222 to prevent MEK phosphorylation
      by RAF. 

PMID- 24746706
TI  - Neurologic manifestations and complications of pandemic influenza A H1N1 in
      Malaysian children: what have we learnt from the ordeal?
AB  - INTRODUCTION: In 2009, pandemic influenza A H1N1 emerged in Mexico and
      subsequently spread worldwide. In Malaysia, there were more than a thousand of
      confirmed cases among children. The general clinical characteristics of these
      children have been well-published. However, the description of neurologic
      complications is scarce. OBJECTIVE: This study aims to describe the
      characteristics of neurologic manifestations and complications in a national
      paediatric cohort with pandemic influenza A H1N1. METHODS: During the pandemic,
      children (12 years or less) admitted for novel influenza A H1N1 in 68 Malaysian
      public hospitals, were prospectively enrolled into national database. The
      clinical, laboratory and neuro-imaging data for children with neurologic
      manifestations, hospitalized from 15th June 2009 till 30th November 2009, was
      reviewed. RESULTS: Of 1244 children with influenza A H1N1 during the study
      period, 103 (8.3%) presented with influenza-related neurological manifestations.
      The mean age of our study cohort was 4.2 years (SD: 3.3 years). Sixty percent of
      them were males. Sixty-nine (66.9%) were diagnosed as febrile seizures, 16
      (15.5%) as breakthrough seizures with underlying epilepsy, 14 (13.6%) as
      influenza-associated encephalopathy or encephalitis (IAE) and 4 (3.9%) as acute
      necrotizing encephalopathy of childhood (ANEC). All 4 available CSF specimens
      were negative for influenza viral PCR. Among 14 children with brain-imaging done,
      9 were abnormal (2: cerebral oedema, 4: ANEC and 3: other findings). There were
      four deaths and three cases with permanent neurological sequelae. CONCLUSION:
      About one-tenth of children with pandemic influenza A H1N1 presented with
      neurologic complications. The most common diagnosis was febrile seizures. One
      fifth of those children with neurologic presentation had IAE or ANEC, which
      carried higher mortality and morbidity. This large national study provides us
      useful data to better manage children with neurologic complications in the future
      pandemic influenza outbreaks.

PMID- 24746705
TI  - Carnitine in severely disabled patients: relation to anthropometric, biochemical
      variables, and nutritional intake.
AB  - BACKGROUND: Carnitine plays a pivotal role in a variety of cellular functions.
      Carnitine deficiency often occurs in severely disabled patients, especially under
      valproic acid administration. However, the possible causative factors underlying
      carnitine deficiency have not been fully identified. The present study aimed at
      clarifying the association of various anthropometric and biochemical variables,
      including dietary intake of carnitine, with carnitine levels in severely disabled
      patients. METHODS: Twenty-six severely disabled patients (mean age: 14.1 years;
      s.d. 7.8) were enrolled. Plasma carnitine levels were evaluated by an enzyme
      cycling assay. Estimation of the dietary intake of carnitine was made based on
      dietary records over a 3-day period. RESULTS: Plasma total and free carnitine
      levels in patients were significantly lower than those in controls obtained from
      the previous report. However, the ratios of free carnitine to total carnitine did
      not change significantly. Free carnitine levels were well correlated with a
      nutritional intake of carnitine. Administration of not only valproic acid but
      also other anti-epileptic drugs was found to cause a significant decrease of free
      carnitine levels after adjusting the nutritional intake of carnitine. Among
      various anthropometric or biochemical variables, albumin and uric acid showed a
      significant correlation with free carnitine levels. CONCLUSIONS: Physicians
      should be aware of the fact that severely disabled patients are at risk for
      carnitine deficiency even in the absence of valproic acid administration, and pay
      more attention to the nutritional intake of carnitine.

PMID- 24746707
TI  - Pancreatic plasmacytoma with biliary obstruction as a manifestation of multiple
      myeloma relapse.

PMID- 24746708
TI  - [Non-invasive markers of fibrosis in the diagnosis of non-alcoholic fatty liver
      disease].
AB  - OBJECTIVE: To analyze the utility of three indices to predict hepatic fibrosis in
      the detection of non-alcoholic fatty liver disease (NAFLD) as a non-invasive
      method in primary care. DESIGN: We performed a descriptive, cross-sectional,
      multicenter study with a populational base from 25 primary care centers in the
      province of Barcelona. PARTICIPANTS: Healthy individuals aged 17 to 83 years
      randomly selected from the Primary Care Computer System. METHODS: Medical
      history, physical examination, and blood analyses were used to determine the
      following predictive indices of fibrosis; HAIR (hypertension, alanine
      aminotransferase, insulin resistance); Fatty Liver Index (FLI) (body mass index,
      gammaglutamyl-transpeptidase, triglycerides, abdominal perimeter) and Lipid
      Accumulation Product (LAP) (triglycerides, abdominal perimeter), and abdominal
      echography. RESULTS: We included 702 individuals; 58% were women and the mean age
      was 53+/-14 years. The FLI was positive in 30.8%, HAIR was positive in 6.7%, and
      LAP was positive in 15.5%. Agreement among the three indices ranged from 63.1% to
      84.9%, with kappa indices between 0.18 and 0.50. A total of 184 individuals met
      the echographic criteria of NAFLD, representing a prevalence of 26.29%. The
      prevalence of NAFLD in patients with positive FLI, HAIR and LAP indices was
      46.8%, 68.1% and 56%, respectively. The index with the greatest sensitivity for
      NAFLD was tFLI>=60 with 84%. Specificity was highest for HAIR and LAP with 97%
      and 91%, respectively. CONCLUSIONS: FLI, HAIR and LAP are highly prevalent and
      have been shown to be independent markers for the diagnosis of NAFLD. Because of
      the lack of concordance between the indices, different prevalences are obtained,
      thus requiring criteria to be unified in order to obtain a more useful index for
      the diagnosis of NAFLD.

PMID- 24746710
TI  - The role of the Eph/ephrin-system in atherosclerotic plaque development: a
      complex puzzle.

PMID- 24746709
TI  - Histopathologic analysis of atrial tissue in patients with atrial fibrillation:
      comparison between patients with atrial septal defect and patients with mitral
      valvular heart disease.
AB  - BACKGROUND: Atrial fibrillation (AF) in adult patients with atrial septal defect
      (ASD) accompanies an enlarged right atrium (RA) with a less enlarged left atrium
      (LA), which is the opposite situation in patients with AF and mitral valvular
      disease. This study was to compare the histopathological change in the atrium of
      patients with AF of two different etiologies: ASD and mitral disease. METHODS:
      Twenty-four patients were enrolled. Group 1 included patients with ASD (8), Group
      2 included patients with ASD with AF (6), and Group 3 included patients with
      mitral disease with AF (10). Preoperative atrial volumes were measured. Atrial
      tissues were obtained during surgical procedures and stained with periodic acid
      Schiff, smooth muscle actin, Sirius red, and Masson's trichrome to detect
      histopathologic changes compatible with AF. The severity of histopathological
      changes was represented with "positivity" and "strong positivity" after analyzing
      digitalized images of the staining. We investigated the relationship between the
      degree of atrial dilatation and severity of histopathological changes according
      to the groups and tissues. RESULTS: Group 2 and Group 3 patients showed a
      tendency toward an enlarged RA volume and enlarged LA volume, respectively,
      compared with each others. However, in the histopathologic analysis, "positivity"
      and "strong positivity" showed no significant positive correlations with the
      degree of atrial volume in special staining. CONCLUSIONS: A similar degree of
      histopathologic changes was observed in both atria in patients with AF (Group 2
      and 3) regardless of the degree of dilatation of atrial volume and disease
      entities.

PMID- 24746711
TI  - An Aggressive Hypoxia Related Subpopulation of Melanoma Cells is TRP-2 Negative.
AB  - Despite existing vaccination strategies targeting TRP-2, its function is not yet
      fully understood. TRP-2 is an enzyme involved in melanin biosynthesis and
      therefore discussed as a differentiation antigen. However, in mice Trp-2 was
      shown to be expressed in melanocyte stem cells of the hair follicle and therefore
      also considered as an indicator of stemness. A proper understanding of the TRP-2
      function is crucial, considering a vaccination targeting cells with stemness
      properties would be highly effective in contrast to a therapy targeting
      differentiated melanoma cells. Analysing over 200 melanomas including primaries,
      partly matched metastases and patients' cell cultures we show that TRP-2 is
      correlated with Melan A expression and decreases with tumor progression. In mice
      it is expressed in differentiated melanocytes as well as in stem cells.
      Furthermore, we identify a TRP-2 negative, proliferative, hypoxia related cell
      subpopulation which is significantly associated with tumor thickness and diseases
      progression. Patients with a higher percentage of those cells have a less
      favourable tumor specific survival. Our findings underline that TRP-2 is a
      differentiation antigen, highlighting the importance to combine TRP-2 vaccination
      with other strategies targeting the aggressive undifferentiated hypoxia related
      subpopulation. 

PMID- 24746712
TI  - A Phase I Protocol of Hydralazine and Valproic Acid in Advanced, Previously
      Treated Solid Cancers.
AB  - Smokers experience aberrant gene promoter methylation in their bronchial cells,
      which may predispose to the development of neoplasia. Hydralazine is a DNA
      demethylating agent, and valproic acid is a histone deacetylase inhibitor, and
      both have modest but synergistic anticancer activity in vitro. We conducted a
      phase I trial combining valproic acid and hydralazine to determine the maximally
      tolerated dose (MTD) of hydralazine in combination with a therapeutic dose of
      valproic acid in patients with advanced, unresectable, and previously treated
      solid cancers. Twenty females and nine males were enrolled, with a median age of
      57 years and a median ECOG performance status of 0. Grade 1 lymphopenia and
      fatigue were the most common adverse effects. Three subjects withdrew for
      treatment-related toxicities occurring after the DLT observation period,
      including testicular edema, rash, and an increase in serum lipase accompanied by
      hyponatremia in one subject each. A true MTD of hydralazine in combination with
      therapeutic doses of valproic acid was not reached in this trial, and the planned
      upper limit of hydralazine investigated in this combination was 400 mg/day
      without grade 3 or 4 toxicities. A median number of two treatment cycles were
      delivered. One partial response by Response Evaluation Criteria In Solid Tumors
      criteria was observed, and five subjects experienced stable disease for 3 to 6
      months. The combination of hydralazine and valproic acid is simple, nontoxic, and
      might be appropriate for chemoprevention or combination with other cancer
      treatments. This trial supports further investigation of epigenetic modification
      as a new therapeutic strategy.

PMID- 24746713
TI  - Colour stainability of indirect CAD-CAM processed composites vs. conventionally
      laboratory processed composites after immersion in staining solutions.
AB  - OBJECTIVES: The aim of this study was to determine, by using a spectrophotometer
      device, the colour stainability of two indirect CAD/CAM processed composites in
      comparison with two conventionally laboratory-processed composites after being
      immersed 4 weeks in staining solutions such as coffee, black tea and red wine,
      using distilled water as control group. METHODS: Two indirect CAD/CAM composites
      (Lava Ultimate and Paradigm MZ100) and two conventionally laboratory-processed
      composites (SR Adoro and Premise Indirect) of shade A2 were selected (160 disc
      samples). Colour stainability was measured after 4 weeks of immersion in three
      staining solutions (black tea, coffee, red wine) and distilled water. Specimen's
      colour was measured each week by means of a spectrophotometer (CIE L*a*b*
      system). Statistical analysis was carried out performing repeated ANOVA
      measurements and Tukey's HSD test to evaluate differences in DeltaE00
      measurements between groups; the interactions among composites, staining
      solutions and time duration were also evaluated. RESULTS: All materials showed
      significant discoloration (p<0.01) when compared to control group. The highest
      DeltaE00 observed was with red wine, whereas black tea showed the lowest one.
      Indirect laboratory-processed resin composites showed the highest colour
      stability compared with CAD/CAM resin blocks. CONCLUSIONS: CAD/CAM processed
      composites immersed in staining solutions showed lower colour stability when
      compared to conventionally laboratory-processed resin composites. CLINICAL
      SIGNIFICANCE: The demand for CAD/CAM restorations has been increasing; however,
      colour stainability for such material has been insufficiently studied. Moreover,
      this has not been performed comparing CAD/CAM processed composites versus
      laboratory-processed indirect composites by immersing in staining solutions for
      long immersion periods.

PMID- 24746714
TI  - Comparison of pattern of failure of resin composite restorations in non-carious
      cervical lesions with and without occlusal wear facets.
AB  - OBJECTIVES: Many studies have reported the clinical problems associated with
      resin composite restorations in NCCLs. None has compared these clinical problems
      in NCCLs with and without occlusal wear facets. The present study sets out to
      determine the proportion of NCCLs that presents occlusal wear facets, and to
      compare the failure pattern of resin composite restorations in NCCLs with and
      without occlusal wear facets. METHODS: Teeth with NCCLs were classified into two
      groups, those with and without occlusal wear facets. Both groups were restored
      using micro hybrid resin composite. The restorations were evaluated at the end of
      2 years concerning post-operative sensitivity, retention, marginal integrity,
      marginal discolouration, wear, and secondary caries, using the USPHS criteria.
      Statistical analysis compared the ratings of each criterion between the two
      groups using Pearson's chi(2) or Fisher's exact test. RESULTS: About one-third
      (33.8%) of teeth with NCCLs presented with occlusal wear facets, more NCCLs with
      occlusal wear facets in mandibular teeth (44.7%) than maxillary teeth (24.5%).
      Retention rate of composite resin restorations in NCCLs with and without occlusal
      wear facets was 63.9% and 74.4% respectively at the end of 2 years. More marginal
      discolouration and defects were observed in restorations in NCCLs with occlusal
      wear facets, the differences were not statistically significant (p>0.05).
      CONCLUSIONS: The decline in ratings of marginal discolouration and defects, and
      the lower retention rate of restorations in NCCLs with occlusal wear facets may
      support the role of occlusal stress and tooth flexure as a cause of failure of
      restorations in NCCLs. CLINICAL SIGNIFICANCE: The ability to distinguish between
      stress induced lesions (with occlusal wear facets) and other cervical lesions
      will have important ramifications for the success of their restorations because
      they are not subjected to the same physical forces that are responsible for the
      deterioration of the restoration.

PMID- 24746715
TI  - 15N chemical shift referencing in solid state NMR.
AB  - Solid-state NMR spectroscopy has much advanced during the last decade and
      provides a multitude of data that can be used for high-resolution structure
      determination of biomolecules, polymers, inorganic compounds or macromolecules.
      In some cases the chemical shift referencing has become a limiting factor to the
      precision of the structure calculations and we have therefore evaluated a number
      of methods used in proton-decoupled (15)N solid-state NMR spectroscopy. For (13)C
      solid-state NMR spectroscopy adamantane is generally accepted as an external
      standard, but to calibrate the (15)N chemical shift scale several standards are
      in use. As a consequence the published chemical shift values exhibit considerable
      differences (up to 22 ppm). In this paper we report the (15)N chemical shift of
      several commonly used references compounds in order to allow for comparison and
      recalibration of published data and future work. We show that (15)NH4Cl in its
      powdered form (at 39.3 ppm with respect to liquid NH3) is a suitable external
      reference as it produces narrow lines when compared to other reference compounds
      and at the same time allows for the set-up of cross-polarization NMR experiments.
      The compound is suitable to calibrate magic angle spinning and static NMR
      experiments. Finally the temperature variation of (15)NH4Cl chemical shift is
      reported.

PMID- 24746716
TI  - Distribution of Malassezia species in patients with pityriasis versicolor in
      Turkey.
AB  - Pityriasis versicolor is a common superficial mycotic disease of the skin which
      is caused by different species of Malassezia genus. The aim of this study was to
      contribute to the knowledge of the aetiology of pityriasis versicolor (PV) with a
      mycological study made according to the new species and additionally, the success
      of the different sampling techniques, duration and recurrence history of the
      disease, distribution of infecting strains according to the affected body sites
      were also investigated. In total, 146 patients with pityriasis versicolor were
      included in this study. Fungal elements could only be visualized by potassium
      hydroxide examination in 36.4% of the samples. Specimens obtained by scraping
      skin surface by a sterile scalpel and/or sterile sticky plaster (OpSite) were
      inoculated in plates containing modified Dixon's medium. Out of 146 samples, 109
      (74.7%) yielded a growth which was considered to be Malassezia spp. in culture.
      Species level identification of suspicious Malassezia yeasts was made according
      to their macroscopic and microscopic features, and their physiological
      characteristics. Among the identified species, Malassezia globosa (65.1%) was the
      most commonly isolated species, followed by Malassezia obtusa (17.4%). However,
      four Malassezia isolates could not be identified at species level with
      conventional methods. While most of the patients suffered their first episode of
      pityriasis versicolor (76%), back of the trunk was the mostly affected body site
      (39%). In conclusion, Malassezia globosa was found to be the predominant species
      in pityriasis versicolor patients in our region, and culture of the specimen is
      necessary for the epidemiologic purposes. 

PMID- 24746717
TI  - Antifungal activity of silver ion on ultrastructure and production of aflatoxin
      B1 and patulin by two mycotoxigenic strains, Aspergillus flavus OC1 and
      Penicillium vulpinum CM1.
AB  - OBJECTIVE: The antifungal activity of silver ion from silver nitrate solution was
      tested against two pathogenic and toxigenic fungal strains. The first was
      Aspergillus flavus OC1, a clinical aflatoxigenic strain that causes fungal
      keratitis and the second was Penicillium vulpinum CM1, a maize-pathogenic strain
      that is positive for patulin (PAT) producing ability. MATERIALS AND METHODS: Agar
      well diffusion assays on yeast sucrose (YES) agar were applied for determination
      of the antifungal activity of silver ions either filter- or autoclaved
      sterilized. Transmission electron microscopy was used to analyze the cellular
      effects of silver ion. The mycotoxins AFB1 and PAT were analyzed in the fungal
      strains cultures treated with silver ion. RESULTS: Filter-sterilized ions have a
      greater potential for growth inhibition of both fungal strains than autoclaved
      sterilized ions. The minimal inhibitory concentration of the filter-sterilized
      ions against A. flavus OC1 was 70 MUg mL(-1) and against P. vulpinum CM1 was 60
      MUg mL(-1) and that the minimum fungicidal concentration was 120 MUg mL(-1)
      against the first strain and 80 MUg mL(-1) against the second strain. Hyphal
      cells treated with silver ion showed considerable changes in the nature of cell
      membranes and cytoplasmic organelles. Silver applied to YES broth inhibited
      mycelial growth and AFB1 and PAT formation of both strains. Growth and mycotoxin
      production appeared to be correlated processes. CONCLUSION: These findings
      indicate the future possibility to use silver ion as substitute for synthetic
      fungicides to control the growth of pathogenic fungi and their mycotoxin
      production.

PMID- 24746718
TI  - [Pseudo-tumoral Aspergillus rhinosinusitis of dental origin].
AB  - INTRODUCTION: Sinonasal aspergillosis is caused by the interaction between the
      sinonasal mucosa with a cosmopolite fungus (Aspergillus), it is on the increase,
      this is an infection whose evolution is unpredictable requiring early diagnosis
      and appropriate support. We report a case of Aspergillus rhinosinusitis of dental
      origin in pseudo-tumoral form with a review of the literature. CLINICAL CASE: A
      31 years-old, women, consulted for a right nasal obstruction with purulent
      rhinorrhea after dental treatment. On examination, there was a bulge of the inner
      canthus of the right eye and a mass in the right nasal cavity. The CT scanner
      showed a process of the left naso-sinus cavity centered by calcic image density.
      The patient underwent a total excision of the mass endoscopically. Mycological
      and pathological examination concluded that the etiology was Aspergillus
      fumigatus. The patient had not received any antifungal treatment. The
      postoperative course was uneventful. The evolution was favourable with no
      recurrence after 9 months. DISCUSSION: Aspergillus rhinosinusitis of dental
      origin is usually due to the emergence of canalicular filling paste into the
      maxillary sinus through and oral cavity and sinus fistula, neglected it can
      progress to invasive pseudo-tumoral form. The clinical presentation is
      nonspecific and the diagnosis often involves imaging (scanner). Mycological and
      histological examinations are essential for diagnosis. The treatment is based on
      surgery sometimes associated with antifungal treatment.

PMID- 24746719
TI  - Genotypic variation and antifungal susceptibly of Candida zeylanoides clinical
      isolates.
AB  - OBJECTIVE: To investigate the DNA fingerprinting of Candida zeylanoides (C.
      zeylanoides) strains and the correlation between genotyping and antifungal
      susceptibility of C. zeylanoides. METHODS: Paper discs containing nystatin,
      ketoconazole, fluconazole, Zataria multiflora (Z. multiflora) and Pulicaria
      gnaphalodes (P. gnaphalodes) essential oils were used in the disc diffusion
      method to evaluate the in vitro activity of the antifungal agents by measuring
      the mean diameter of inhibition around the discs. Yeast isolates were
      characterized by randomly amplified polymorphic DNA (RAPD) analysis using two
      different primers. RESULTS: The mean inhibition zones were calculated 36.1 +/-
      2.2mm for ketoconazole, 25.3 +/- 2.0mm for nystatin and 14.9 +/- 1.4mm for
      fluconazole. Z. multiflora essential oil revealed a 58.6 +/- 2.6mm mean zone of
      inhibition while P. gnaphalodes showed a 36.7 +/- 1.8mm zone of inhibition
      against all isolates tested. A total of 14 strains of C. zeylanoides were divided
      into three types, 1 was genotype A strain, 2 genotype B strains and 11 genotype C
      strains. Strain of genotype A was significantly more susceptible to ketoconazole
      and nystatin than fluconazole (P<0.05). Strains of genotype B were more
      susceptible to ketoconazole than other antifungal agents (P>0.05). Strains of
      genotype C were significantly more susceptible to ketoconazole than fluconazole
      and nystatin (P<0.05). There was a significant correlation between C. zeylanoides
      genotypes and antifungal susceptibility (P < 0.05). CONCLUSION: We concluded that
      all C. zeylanoides genotypes were susceptible to nystatin and Z. multiflora
      essential oil. The correlation between antifungal susceptibility and C.
      zeylanoides genotype may be of potential therapeutic significance and larger
      studies are needed to prove this finding.

PMID- 24746720
TI  - Antifungal activity of a soil isolate of Pseudomonas chlororaphis against
      medically important dermatophytes and identification of a phenazine-like compound
      as its bioactive metabolite.
AB  - OBJECTIVE: The increasing importance of dermatophytoses and emerging resistance
      of dermatophytes to current synthetic antifungals have stimulated the search for
      safer and more effective alternative drugs from natural sources. The present
      study was carried out to identify antagonistic bacteria of soil origin with
      strong inhibitory activities on the growth of major human pathogenic
      dermatophytes. MATERIALS AND METHODS: Antifungal activity of isolated soil
      bacteria was screened against the dermatophytes from three genera Microsporum (M.
      canis, M. gypseum), Epidermophyton (E. floccosum) and Trichophyton (T.
      mentagrophytes, T. rubrum, T. violaceum, T. tonsurans) by using visual plate agar
      assay method. A Pseudomonas chlororaphis isolate S105, identified at the species
      level by 16S ribosomal RNA sequence analysis, was reported as the strongest
      antagonistic bacterium. P. chlororaphis S105 culture supernatant (PCCS) was
      examined against tested dermatophytes by GY (glucose-yeast extract) broth
      bioassay in 6-well microplates. Antifungal compound of the bacterium was
      partially purified from the culture supernatant through a purification scheme of
      methanol extraction, Diaion HP20 ion-exchange chromatography and preparative thin
      layer chromatography. RESULTS: P. chlororaphis S105 was the most potent inhibitor
      of fungal growth for all tested dermatophytes with a percent inhibition ranged
      from 57.1% to 99.8%. The PCCS suppressed the growth of all fungi tested in the
      range of 18.5% to 84.8%. Partially purified antifungal compound of the bacterium
      was identified as a phenazine-like compound with an Rf value of 0.51. The
      compound inhibited fungal growth by 73.6% to 97.9% on GY broth. Fungal growth
      inhibition was significant for all dermatophytes tested in comparison with the
      controls (Anova, P<0.05). CONCLUSION: With respect to the strong inhibitory
      activity of P. chlororaphis against pathogenic dermatophytes reported here, it
      may be considered as a rich source of useful metabolites with potential
      application in antifungal drug discovery.

PMID- 24746721
TI  - Purification and characterization of antifungal phenazines from a fluorescent
      Pseudomonas strain FPO4 against medically important fungi.
AB  - The strain FPO4 was isolated from the rhizoplane of rice plant root and
      identified as a fluorescent Pseudomonas aeruginosa on the basis of 16S rDNA
      sequences and BLAST analysis. The extracellular metabolites produced by this
      strain were purified by silica gel column chromatography and isolated four pure
      compounds. Based on the spectral data the four compounds were identified as
      phenazin-1-ol, phenazine-1-carboxylic acid (PCA), 2-heptyl-3-hydroxyl-4(1H)
      quinolone (PQS), and phenazine-1-carboxamide (PCN), respectively. Phenazin-1-ol
      and PCA were active against all the eight fungi tested. The highest activity of 4
      MUg/mL by PCA was recorded against Trichophyton rubrum, a human pathogen
      responsible for causing athlete's foot, jock itch, ringworm and fingernail fungus
      infections, followed by Candida albicans and Candida tropicalis. The activity of
      phenazin-1-ol, PCA against Candida spp. was found to be better than the standard
      antifungal agent amphotericin B. Furthermore, the present study reports the
      antimicrobial activity of the purified phenazines on major human pathogen, T.
      rubrum for the first time.

PMID- 24746722
TI  - Potential effects of Trachyspermum copticum essential oil and propolis alcoholic
      extract on Mep3 gene expression of Microsporum canis isolates.
AB  - OBJECTIVE: The purpose of this study was to evaluate the effects of Trachyspermum
      copticum (T. copticum) essential oil and propolis alcoholic extract on growth and
      transcription of Mep3 gene of Microsporum canis (M. canis) strains. METHODS: The
      antifungal activity was assayed by broth macrodilution method. Fungal isolates
      were grown in soy peptone liquid medium and treated with T. copticum oil and
      propolis extract. Total RNAs of M. canis were subjected to reverse transcription
      polymerase chain reaction (RT-PCR). Specific primers of Actin and Mep3 genes were
      used. RESULTS: The results revealed that MIC values of T. copticum oil against M.
      canis strains were ranged from 0.2-30.5 MUg/mL, with 42.3% of the strains
      inhibited at 0.9 MUg/mL. In addition, MIC values of propolis extract against M.
      canis strains were ranged from 0.2-488.2 MUg/mL, with 34.6% of the strains
      inhibited at 0.9 MUg/mL. RT-PCR analysis of Mep3 and Actin expression showed DNA
      fragments of 661 and 690 bp amplified in all isolates before treatments with T.
      copticum essential oil and propolis extract. Both T. copticum and propolis
      completely inhibited the expression of Mep3 gene. CONCLUSION: We reported for the
      first time that T. copticum and propolis inhibits the expression of Mep3 gene in
      M. canis strains in relation to a remarkable inhibition in protease production by
      the fungus.

PMID- 24746723
TI  - [Epidemiology of Tinea capitis in the suburbs of Tipasa, Algeria].
AB  - Tinea capitis represent a public health problem in Algeria, despite improvement
      of living conditions. We conducted a retrospective study of cases diagnosed in
      the hospital Hadjout (Tipasa), Algeria, during 3 years (January 2010-January
      2013). RESULT: Among a total of 213 hair samples, 133 were positive (direct
      examination or culture). Incidence average was 44 cases per year. Patients were
      under 12 years of age in 91%. Three species of dermatophytes were isolated:
      Trichophyton violaceum (66%), Microsporum canis (32.5%) and Trichophyton
      mentagrophytes (1.5%). No favus was diagnosed during the study period.

PMID- 24746724
TI  - Epidemiology of tinea capitis in northern Tunisia.

PMID- 24746725
TI  - Species distribution and susceptibility of Candida isolates from patient with
      vulvovaginal candidiasis in Southern China from 2003 to 2012.
AB  - OBJECTIVE: To determine the Candida species involved and the antifungal
      susceptibility of Candida species isolated from patients with vulvovaginal
      candidiasis (VVC). MATERIALS AND METHODS: Candida organisms were cultured from
      samples obtained from patients with VVC at Gynecology Department of Peking
      University Shenzhen Hospital from April 2003 to September 2012. Antifungal
      susceptibility testing was performed using a commercial agar diffusion test.
      RESULTS: A total of 3181 yeasts isolates, mostly Candida, were obtained from 3141
      patients with VVC. Two species of Candida were isolated from each of 40 patients
      (1.3%, 40/3141). C. albicans were the predominant Candida species (2705 strains,
      85.0%) in VVC, followed by C. glabrata (337 strains, 10.6%), C. parapsilosis (49
      strains, 1.5%), C. tropicalis (31 strains, 1.0%), Saccharomyces cerevisiae (23
      strains, 0.7%), C. krusei (15 strains, 0.5%), Candida famata (11 strains, 0.4%),
      Rhodotorula sp. (6 strains, 0.2%), and C. lusitaniae (2 strains, 0.1%).
      Antifungal susceptibility was tested in a total of 1942 strains from patients
      with VVC. All of the C. albicans isolates obtained were susceptible to nystatin.
      The resistant rate of C. albicans to fluconazole, itraconazole, miconazole,
      clotrimazole was 1.1% (18/1612), 2.2% (36/1612), 4.2% (68/1612), and 0.9%
      (14/1612). The resistant rate of non-albicans to fluconazole, itraconazole,
      miconazole, and clotrimazole was 11.8% (39/329), 2.5% (8/329), 1.8% (6/329), and
      4.3% (14/329). CONCLUSIONS: C. albicans was the predominant Candida species
      isolated from this series of patients with VVC. Resistance of vaginal C. albicans
      isolates to antifungal agents was infrequent.

PMID- 24746726
TI  - Synergistic activity between Echinophora platyloba DC ethanolic extract and azole
      drugs against clinical isolates of Candida albicans from women suffering chronic
      recurrent vaginitis.
AB  - OBJECTIVE: Candida albicans is one of the main causes of vaginitis, especially in
      women with recurrent episodes. The appearance of drug resistant C. albicans and
      adverse effects of chemical agents have raised interest in Echinophora platyloba
      as one of four native species in Traditional Persian-Iranian medicine. MATERIALS
      AND METHODS: This study evaluates the antifungal activity of ethanolic extract
      from dried aerial parts of E. platyloba against 27 clinical isolates of C.
      albicans from women suffering chronic recurrent vaginitis by micro-broth dilution
      assay. The synergistic effect of azole drugs and E. platyloba ethanolic extract
      were also determined by disc diffusion method after determining the MIC90.
      RESULTS: The results of this study showed a potent synergistic effect of E.
      platyloba ethanolic extract and itraconazole (P<0.01) and fluconazole (P<0.001)
      but an antagonistic effect between E. platyloba ethanolic extract and
      clotrimazole and miconazole against clinical isolates of C. albicans. CONCLUSION:
      These results must be confirmed by clinical application and by further clinical
      studies.

PMID- 24746727
TI  - Epidemiology of tinea capitis among school-age children in Meiganga, Cameroon.
AB  - Tinea capitis (TC) commonly called scalp ringworm is a worldwide concern and a
      public health problem in Africa. This study aimed at determining the
      epidemiologic profile of TC among school-aged children in the savanna zone of
      Cameroon. All children present at school during this study period, August 2011
      July 2012, were examined for signs suggestive of TC. Children not registered at
      school were excluded from the study. Pathologic specimens were taken from
      suspected head lesions and cultured. Amongst the 4601 children, average age
      10.7+/-0.16 years, 377 presented with suggestive TC lesions giving a prevalence
      of 8.1%. The proportion of boys with TC was (63.7%) higher than in girls (36.3%)
      (P<=0.05). TC manifestations varied; small plaques of alopecia 59.26% were the
      most frequent. Communal living was the most incriminated risk factor. Three
      hundred and thirty six isolates were obtained in culture. The prevalence was
      significantly higher (P<0.05) in age range between 8 and 12 years, followed by
      that between 13 and 15. The most prevalent isolate was T. soudannense 56.8%,
      followed by T. rubrum 29.2%. Only 6.0% of the isolates belonged to the genus
      Microsporum.

PMID- 24746728
TI  - Clinical and mycological evaluation of an herbal antifungal formulation in canine
      Malassezia dermatitis.
AB  - OBJECTIVE: Malassezia pachydermatis is a common cause of more widespread
      dermatitis in dogs (CMD). Recurrences are common, and this disorder can be very
      troubling for both dogs and for the pet owner. MATERIAL AND METHODS: The
      treatment of 20 dogs affected by dermatitis due to M. pachydermatis, with
      Malacalm((r)), a commercially available mixture consisting of essential oils
      (Citrus aurantium 1%, Lavandula officinalis 1%, Origanum vulgare 0.5%, Origanum
      majorana 0.5%, Mentha piperita 0.5% and Helichrysum italicum var. italicum 0.5%,
      in sweet almond oil and coconut oil) is reported. The effectiveness of the whole
      mixture, of component essential oils and of their more represented compounds
      against clinical isolates was evaluated by a microdilution test. Twenty animals
      were topically administered the mixture twice daily for 1 month. Ten animals were
      treated with a conventional therapy based on ketoconazole 10mg/kg/day and
      chlorhexidine 2% twice a week for 3 weeks. At the end of both treatments animals
      significantly improved their clinical status. Adverse effects were never noticed.
      Follow-up visit performed on day 180th allowed to observe a recurrence of
      clinical signs in all the subjects treated conventionally, while not significant
      clinical changes were referred in dogs treated with Malacalm((r)). The overall
      MIC value of Malacalm((r)) was 0.3%. O. vulgare showed the lowest minimum
      inhibitory concentrations (MIC), being active at 0.8%, followed by M. piperita
      (1%), O. majorana (1.3%), C. aurantium (2%) and L. officinalis (4%) while H.
      italicum did not yield any antimycotic effect up to 10%. Active major compounds
      were thymol, carvacrol, p-cymene, 1,8-cineol, limonene and menthol. CONCLUSION:
      The phytotherapic treatment achieved a good clinical outcome, and no recurrence
      of skin disorders on day 180th was recorded. This herbal remedium appeared to be
      a safe tool for limiting recurrences of CMD.

PMID- 24746729
TI  - [Extensive inflammatory and childhood dermatophytosis caused by Trichophyton
      rubrum].
AB  - We report an observation of extensive and atypical dermatophytosis to
      Trichophyton rubrum coexisting with fingernails and tinea manuum candidiasis in a
      13-year-old girl presenting inflammatory cutaneous lesions, involvement of scalp,
      as well as total dystrophic onychomycosis of feet associated with a perionyxis of
      hands. The results of the mycological examination of specimen showed fungal
      elements of septate hyphae and pilar parasitism. The fungal culture allowed the
      diagnosis of certainty of the dermatophytosis to T. rubrum. The therapeutic
      success of this infection was obtained thanks to the administration of
      antifungals by oral route. 

PMID- 24746730
TI  - Watering down a theory: Comment on "Fluctuations in the DNA double helix: A
      critical review" by Frank-Kamenetskii & Prakash.

PMID- 24746731
TI  - Minireview: Metabolic control of the reproductive physiology: insights from
      genetic mouse models.
AB  - This article is part of a Special Issue Energy Balance. Over the past two
      decades, and in particular over the past 5-7 years, there has been a tremendous
      advancement in the understanding of the metabolic control of reproductive
      physiology. This has been in large part due to the advancement and refinement of
      gene targeting tools and techniques for molecular mapping. Yet despite the
      emergence of exciting and often times thought-provoking data through the use of
      new mouse models, the heavy reliance on gene targeting strategies has become
      fundamental in this process and thus caution must be exercised when interpreting
      results. This minireview article will explore the generation of new mouse models
      using genetic manipulation, such as viral vector delivery and the use of the
      Cre/loxP system, to investigate the role of circulating metabolic hormones in the
      coordination of reproductive physiology. In addition, we will also highlight some
      of the pitfalls in the use of genetic manipulation in the current paradigms.
      However, it has become clear that metabolic cues employ integrated and plastic
      neural circuits in order to modulate the neuroendocrine reproductive axis, and
      despite recent advances much remains to be elucidated about this circuitry. 

PMID- 24746732
TI  - Peripheral androgen receptor gene suppression rescues disease in mouse models of
      spinal and bulbar muscular atrophy.
AB  - Spinal and bulbar muscular atrophy (SBMA) is caused by the polyglutamine androgen
      receptor (polyQ-AR), a protein expressed by both lower motor neurons and skeletal
      muscle. Although viewed as a motor neuronopathy, data from patients and mouse
      models suggest that muscle contributes to disease pathogenesis. Here, we tested
      this hypothesis using AR113Q knockin and human bacterial artificial
      chromosome/clone (BAC) transgenic mice that express the full-length polyQ-AR and
      display androgen-dependent weakness, muscle atrophy, and early death. We
      developed antisense oligonucleotides that suppressed AR gene expression in the
      periphery but not the CNS after subcutaneous administration. Suppression of polyQ
      AR in the periphery rescued deficits in muscle weight, fiber size, and grip
      strength, reversed changes in muscle gene expression, and extended the lifespan
      of mutant males. We conclude that polyQ-AR expression in the periphery is an
      important contributor to pathology in SBMA mice and that peripheral
      administration of therapeutics should be explored for SBMA patients. 

PMID- 24746733
TI  - Efficient transgene expression by alleviation of translational repression in
      plant cells.
AB  - Global translational repression under abiotic stress influences translation of
      both endogenous and transgene mRNAs. Even in plant cell culture, hypoxia and
      nutrient deficient stress arise during the growth process. In this study, we
      first demonstrated the existence of global translational repression in
      Arabidopsis T87 cultured cells over a time course following inoculation. Next, we
      performed genome-wide analysis, which revealed that the translational states of
      endogenous mRNAs differed significantly between growth and stationary phase
      cells. This analysis showed that translation from most mRNAs was repressed upon
      stationary phase. Otherwise, a part of mRNA including alcohol dehydrogenase (ADH)
      gene was recalcitrant to the repression. Furthermore, by polysome analysis and
      followed quantitative reverse transcription PCR analysis of transformants having
      5'untranslated regions (UTRs) of ADH or translationally repressed At3g47610 mRNA
      fused to reporter gene, we demonstrated that polysomal associations of reporter
      mRNAs were in accordance with those the mRNAs from which their 5'UTR derived,
      suggesting that the 5'UTR is an important determinant of the translational state
      of mRNAs in stationary phase cells. Finally, we demonstrated the effectiveness of
      5'UTR of ADH mRNA in transformants derived from the BY-2 tobacco cell line. These
      results suggested that 5'UTR of ADH mRNA would be a useful element for efficient
      transgene expression upon stationary phase. 

PMID- 24746734
TI  - Probing of exopolysaccharides with green fluorescence protein-labeled
      carbohydrate-binding module in Escherichia coli biofilms and flocs induced by
      bcsB overexpression.
AB  - Polysaccharides are major structural constituents to develop the three
      dimensional architecture of Escherichia coli biofilms. In this study, confocal
      laser scanning microscopy was applied in combination with a fluorescent probe to
      analyze the location and arrangement of exopolysaccharide (EPSh) in microcolonies
      of E. coli K-12 derived strains, formed as biofilms on solid surfaces and flocs
      in the liquid phase. For this purpose, a novel fluorescent probe was constructed
      by conjugating a carbohydrate-binding module 3, from Paenibacillus
      curdlanolyticus, with the green fluorescence protein (GFP-CBM3). The GFP-CBM3
      fused protein exhibited strong affinity to microcrystalline cellulose. Moreover,
      GFP-CBM3 specifically bound to cell-dense microcolonies in the E. coli biofilms,
      and to their flocs induced by bcsB overexpression. Therefore, the fused protein
      presents as a novel marker for EPSh produced by E. coli cells. Overexpression of
      bcsB was associated with abundant EPSh production and enhanced E. coli biofilm
      formation, which was similarly detectable by GFP-CBM3 probing. 

PMID- 24746735
TI  - Novel thrombolytic protease from edible and medicinal plant Aster yomena (Kitam.)
      Honda with anticoagulant activity: purification and partial characterization.
AB  - A thrombolytic protease named kitamase possessing anticoagulant property was
      purified from edible and medicinal plant Aster yomena (Kitam.) Honda. Kitamase
      showed a molecular weight of 50 kDa by SDS-PAGE and displayed a strong fibrin
      zymogram lysis band corresponding to the similar molecular mass. The enzyme was
      active at high temperatures (50 degrees C). The fibrinolytic activity of kitamase
      was strongly inhibited by EDTA, EGTA, TPCK and PMSF, inhibited by Zn(2+). The Km
      and Vmax values for substrate S-2251 were determined as 4.31 mM and 23.81 mM/mg
      respectively. It dissolved fibrin clot directly and specifically cleaved the
      alpha, Aalpha and gamma-gamma chains of fibrin and fibrinogen. In addition,
      kitamase delayed the coagulation time and increased activated partial
      thromboplastin time and prothrombin time. Kitamase exerted a significant
      protective effect against collagen and epinephrine induced pulmonary
      thromboembolism in mice. These results suggest that kitamase may have the
      property of metallo-protease like enzyme, novel fibrino(geno)lytic enzyme and a
      potential to be a therapeutic agent for thrombosis. 

PMID- 24746736
TI  - Compliance with recommendations of clinical practice in the management of venous
      thromboembolism in cancer: the CARMEN study.
AB  - Cancer is associated with venous thromboembolism in 20% of patients. In such
      patients, thrombosis is difficult to treat, associated with bleeding, recurrence,
      and death. Specific treatments for venous thromboembolism in cancer are
      recommended. Guidelines have been implemented in many countries and international
      guidelines have been recently developed. We evaluated the adhesion to national
      French guidelines via a survey of cancer patients treated for venous
      thromboembolism. METHODS: A national cross-sectional observational study
      evaluated the adhesion to guidelines in hospitalized patients. Good clinical
      practice was defined as initial 10-day treatment with injectable molecules
      followed by long-term treatment with low molecular weight heparin for at least 3
      months. Demographic data, cancer type, stage, treatment, risk factors and type of
      thrombosis, were recorded. RESULTS: Five patients were included in 47 centers.
      Overall adhesion to guidelines was present in 59% (55-63%) of patients (295/500).
      During initial treatment, adhesion was high (487/496; 98%) but dropped (296/486;
      62%) during the long-term maintenance. In patients with renal insufficiency, only
      a fourth of them received the adequate treatment. A majority of patients had
      metastatic disease (64%). Cancer sites were gastro-intestinal (25%), gynecologic
      (23%), pulmonary (21%), hematological (14%), urologic (10%), or other (8%). Lung
      and hematological malignancies were significantly associated with the highest and
      lowest rates of adhesion. CONCLUSION: Adhesion to national guidelines for
      treatment of venous thromboembolism in cancer is not optimal. Good compliance is
      observed during initial treatment, but drops after 10 days, underlying the need
      for further education to achieve a better implementation on a national level.

PMID- 24746737
TI  - Characterization of follicle stimulating hormone profiles in normal ovulating
      women.
AB  - OBJECTIVE: To describe FSH profile variants. DESIGN: Observational study.
      SETTING: Multicenter collaborative study. PATIENT(S): A total of 107 women.
      INTERVENTION(S): Women collected daily first morning urine and underwent serial
      ovarian ultrasound. MAIN OUTCOME MEASURE(S) FSH RESULT(S): The individual FSH
      cyclic profiles demonstrated a significant departure from the currently accepted
      model. A decline in FSH levels at the end of the follicular phase was observed in
      only 42% of cycles. The absence of this decline was significantly associated with
      a shorter luteal phase and higher pregnanediol-3alpha-glucuronide, FSH, and LH
      levels at the time of ovulation. In 34% of the cycles, significant FSH
      variability was observed throughout the follicular phase; this variability was
      associated with higher body mass index and lower overall FSH and LH levels
      throughout the cycle. The FSH peak occurs on average 2 hours before ovulation.
      The FSH peak duration was shorter than the LH peak. CONCLUSION(S): These results
      suggest that average FSH profiles may not reflect the more complex dynamics of
      daily hormonal variations in the menstrual cycle. It is possible that
      discrepancies between the average normal FSH profile and the individual day-to
      day variants can be used to detect abnormalities.

PMID- 24746738
TI  - Conjugated bisphenol A in maternal serum in relation to miscarriage risk.
AB  - OBJECTIVE: To examine the relationship between the maternal serum bisphenol A
      (BPA) concentration at the time of the missed menstrual cycle and miscarriage
      risk. DESIGN: Retrospective cohort of prospectively collected serum samples.
      SETTING: Academic fertility center. PATIENT(S): Women presenting for early
      pregnancy monitoring with singleton pregnancies. INTERVENTION(S): Stored serum
      samples from 4 to 5 weeks' gestation analyzed for conjugated serum BPA
      concentrations. MAIN OUTCOME MEASURE(S): Live birth, miscarriage, and chromosome
      content of miscarriage. RESULT(S): With the 115 women included in the study,
      there were 47 live births and 68 clinical miscarriages (46 aneuploid and 22
      euploid). Median conjugated BPA concentrations were higher in the women who had
      miscarriages than in those who had live births (0.101 vs. 0.075 ng/mL). Women
      with the highest quartile of conjugated BPA had an increased relative risk of
      miscarriage (1.83; 95% CI, 1.14-2.96) compared with the women in the lowest
      quartile. We found a similar increase risk for both euploid and aneuploid
      miscarriages. CONCLUSION(S): Maternal conjugated BPA was associated with a higher
      risk of aneuploid and euploid miscarriage in this cohort. The impact of reducing
      individual exposure on future pregnancy outcomes deserves further study.

PMID- 24746739
TI  - Use of fertility treatment modalities in a large United States cohort of
      professional women.
AB  - OBJECTIVE: To evaluate the use of fertility treatments among a large cohort of
      women in the United States. DESIGN: Cohort study. SETTING: Nurses' Health Study
      II. PATIENT(S): Ten thousand thirty-six women who reported having used fertility
      treatment on biennial questionnaires from 1993-2009. INTERVENTION(S): None. MAIN
      OUTCOME MEASURE(S): Data on patterns of treatment modality were collected via
      self-report from validated mailed questionnaires. Information on clomiphene,
      gonadotropin injections alone, and gonadotropin injections as part of
      intrauterine insemination (IUI) and in vitro fertilization (IVF) was queried.
      RESULT(S): Most women who reported fertility treatment used clomiphene (94%),
      with a large majority reporting clomiphene as their only form of treatment (73%).
      Of women who reported treatment more advanced than clomiphene, 13% had used
      gonadotropin injections alone, 11% IUI treatment, and 11% IVF. Several subgroups
      were more likely to use multiple treatment modalities and to initiate treatment
      with gonadotropins rather than clomiphene, including women living in states with
      insurance coverage of fertility procedures, with higher household income, younger
      in age, who remained nulliparous at the study close, and treated after 2000.
      CONCLUSION(S): Results should be interpreted cautiously, but to our knowledge,
      this represents the first study of fertility treatment patterns in the United
      States and could inform public health planning.

PMID- 24746740
TI  - Does prolonged pituitary down-regulation with gonadotropin-releasing hormone
      agonist improve the live-birth rate in in vitro fertilization treatment?
AB  - OBJECTIVE: To evaluate the effects of a prolonged duration of gonadotropin
      releasing hormone agonist (GnRH-a) in pituitary down-regulation for controlled
      ovarian hyperstimulation (COH) on the live-birth rate in nonendometriotic women
      undergoing in vitro fertilization and embryo transfer (IVF-ET). DESIGN:
      Retrospective cohort study. SETTING: University-affiliated hospital. PATIENT(S):
      Normogonadotropic women undergoing IVF. INTERVENTION(S): Three hundred seventy
      eight patients receiving a prolonged pituitary down-regulation with GnRH-a before
      ovarian stimulation and 422 patients receiving a GnRH-a long protocol. MAIN
      OUTCOME MEASURE(S): Live-birth rate per fresh ET. RESULT(S): In comparison with
      the long protocol, the prolonged down-regulation protocol required a higher total
      dose of gonadotropins. A lower serum luteinizing hormone (LH) level on the
      starting day of gonadotropin and the day of human chorionic gonadotropin (hCG)
      and a fewer number of oocytes and embryos were observed in the prolonged down
      regulation protocol. However, the duration of stimulation and number of high
      quality embryos were comparable between the two groups. A statistically
      significantly higher implantation rate (50.27% vs. 39.69%), clinical pregnancy
      rate (64.02% vs. 56.87%) and live-birth rate per fresh transfer cycle (55.56% vs.
      45.73%) were observed in the prolonged protocol. CONCLUSION(S): Prolonged down
      regulation in a GnRH-a protocol might increase the live-birth rates in
      normogonadotropic women.

PMID- 24746741
TI  - Active and passive smoking and fecundability in Danish pregnancy planners.
AB  - OBJECTIVE: To investigate the extent to which fecundability is associated with
      active smoking, time since smoking cessation, and passive smoking. DESIGN:
      Prospective cohort study. SETTING: Denmark, 2007-2011. PATIENT(S): A total of
      3,773 female pregnancy planners aged 18-40 years. INTERVENTION(S): None. MAIN
      OUTCOME MEASURE(S): Self-reported pregnancy. Fecundability ratios (FRs) and 95%
      confidence intervals (CIs) were estimated using a proportional probabilities
      model that adjusted for menstrual cycle at risk and potential confounders.
      RESULT(S): Among current smokers, smoking duration of >=10 years was associated
      with reduced fecundability compared with never smokers (FR, 0.85, 95% CI 0.72
      1.00). Former smokers who had smoked >=10 pack-years had reduced fecundability
      regardless of when they quit smoking (1-1.9 years FR, 0.83, 95% CI 0.54-1.27; >=2
      years FR, 0.73, 95% CI 0.53-1.02). Among never smokers, the FRs were 1.04 (95% CI
      0.89-1.21) for passive smoking in early life and 0.92 (95% CI 0.82-1.03) for
      passive smoking in adulthood. CONCLUSION(S): Among Danish pregnancy planners,
      cumulative exposure to active cigarette smoking was associated with delayed
      conception among current and former smokers. Time since smoking cessation and
      passive smoking were not appreciably associated with fecundability.

PMID- 24746743
TI  - Age-specific serum antimullerian hormone levels in women with and without
      polycystic ovary syndrome.
AB  - OBJECTIVE: To determine the serum antimullerian hormone (AMH) reference values in
      Chinese women with and without polycystic ovary syndrome (PCOS), and the
      associations of AMH with clinical or biochemical characteristics. DESIGN:
      Retrospective study. SETTING: Academic institutions. PATIENT(S): Totals of 1,896
      infertile control women and 304 women with PCOS. INTERVENTION(S): None. MAIN
      OUTCOME MEASURE(S): Serum basal AMH levels and clinical, endocrine, and metabolic
      parameters. RESULT(S): In the same age group, serum AMH levels were higher in
      PCOS women than those without PCOS. AMH levels were not significantly related to
      indices of insulin resistance or metabolic-related variables in both groups. In
      the infertile control group, AMH increased with antral follicle count (AFC) and
      LH and decreased with age, body mass index (BMI), and FSH. In the PCOS group, AMH
      levels showed positive correlations with LH, AFC, and T and negative correlations
      with BMI. The median AMH levels were 2.35 ng/mL for ages 20-31 years, 1.58 ng/mL
      for ages 32-34 years, 1.30 ng/mL for ages 35-37 years, 0.96 ng/mL for ages 38-40
      years, 1.05 ng/mL for ages 41-43 years, and 0.67 ng/mL for ages>43 years in the
      control group and 4.38 ng/mL for ages 20-31 years, 3.47 ng/mL for ages 32-34
      years, and 3.30 ng/mL for ages 35-37 years in the PCOS group. CONCLUSION(S): This
      study determined reference values of serum AMH in Chinese women with and without
      PCOS. Elevated serum AMH levels do not affect the risk of insulin resistance or
      metabolic syndrome.

PMID- 24746742
TI  - Urinary metabolome identifies signatures of oligozoospermic infertile men.
AB  - OBJECTIVE: To identify the differential urinary metabolic pattern of
      oligozoospermic infertile men and to determine the potential biomarkers
      indicative of infertility. DESIGN: Observational study. SETTING: University
      hospital. PATIENT(S): Totals of 158 fertile volunteers and 135 oligozoospermic
      infertile men. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Urinary metabolic
      profiles were acquired with the use of liquid chromatography/mass spectrometry.
      Potential oligozoospermic biomarkers were screened from orthogonal projections to
      latent structures discriminant analysis and further evaluated by receiver
      operating characteristic analysis. The Spearman correlations between the
      individual sets of biomarkers and between biomarkers and sperm parameters were
      investigated. The disrupted biologic pathways which the biomarkers were involved
      in also were analyzed. RESULT(S): Oligozoospermic infertile men could be
      differentiated from fertile control subjects based on altered urinary metabolic
      profiles. A total of ten potential biomarkers were screened and tentatively
      identified. Among those, decreased acylcarnitines, aspartic acid, and
      leucylproline and increased adenine and methylxanthine were strongly associated
      with oligozoospermic risk. Many biomarkers were associated with sperm
      concentration and amplitude of lateral head displacement. The combined pattern of
      acetylcarnitine, carnitine C3:1, and aspartic acid provided moderate diagnostic
      power. CONCLUSION(S): Urinary metabolomics identified unique metabolic pattern of
      oligozoospermic infertility. The potential biomarkers suggested that
      oligozoospermia may be tightly associated with energy consumption and antioxidant
      defenses in spermatogenesis.

PMID- 24746744
TI  - Peri-implantation intercourse lowers fecundability.
AB  - OBJECTIVE: To determine the impact of sexual intercourse around the time of
      implantation on the probability of achieving a pregnancy. DESIGN: Time-to
      pregnancy cohort using day-specific probability of pregnancy modeling to account
      for intercourse during the fertile window. SETTING: Community cohort. PATIENT(S):
      Women trying to conceive naturally, ages 30-44, without known infertility.
      INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Positive pregnancy test.
      RESULT(S): A total of 564 women provided 1,332 complete cycles for analysis.
      Intercourse frequency during the fertile window and during the peri-implantation
      window were significantly correlated. Cycles in which couples had 2 or more days
      with intercourse during the implantation window were significantly less likely to
      result in a positive pregnancy test compared with cycles in which couples did not
      have intercourse in this window, after adjusting for age, race, history of
      regular menstrual cycles, previous pregnancy, and body mass index (fecundability
      ratio, 0.62; 95% confidence interval, 0.42-0.91). CONCLUSION(S): Intercourse
      during the peri-implantation window may be detrimental to natural fertility.
      Methods that allow couples to time intercourse to the fertile window may decrease
      time to pregnancy by not only increasing the probability of fertilization but
      also decreasing the probability of failed implantation.

PMID- 24746745
TI  - Responding to change in reproductive endocrinology fellowships.

PMID- 24746746
TI  - Interleukin-25 induced by human chorionic gonadotropin promotes the proliferation
      of decidual stromal cells by activation of JNK and AKT signal pathways.
AB  - OBJECTIVE: To clarify the role and mechanism of interleukin (IL)-25 in regulating
      the biological functions of decidual stromal cells (DSCs) in human early
      pregnancy. DESIGN: Laboratory study of the effect of IL-25 induced by hCG on the
      proliferation of DSCs. SETTING: Research laboratories. PATIENT(S): Women aged 23
      47 years with normal pregnancy and abortion. INTERVENTION(S): None. MAIN OUTCOME
      MEASURE(S): Signal transduction from IL-25. RESULT(S): Here we show that DSCs
      coexpress IL-25/IL-17RB. Human chorionic gonadotropin promotes the expression of
      IL-25/IL-17RB. In contrast to anti-human IL-25 neutralizing antibody, recombinant
      human IL-25 (rhIL-25) significantly stimulates the proliferation of DSCs in
      dosage- and time-dependent manners. RhIL-25 promotes the phosphorylation of AKT,
      extracellular-signal-regulated kinases 1/2 (ERK1/2), c-Jun N-terminal kinases
      (JNK), and nuclear factor kappaB in DSCs. Interestingly, blocking JNK or AKT
      signal with inhibitors down-regulates the stimulatory effect on DSC proliferation
      induced by rhIL-25. In addition, the results of Western blot show that the
      expression of IL-25/IL-17RB in DSCs from normal pregnancy was higher than that
      from abortion. CONCLUSION(S): Our results have revealed that hCG derived of
      trophoblasts up-regulates the expression of IL-25/IL-17RB in DSCs and that IL-25
      further stimulates the proliferation of DSCs through activating JNK and AKT
      signals, which finally contributes to the establishment and maintenance of
      physiological pregnancy.

PMID- 24746747
TI  - Patterns of practice in palliative radiotherapy in Africa - case revisited.
AB  - AIMS: To investigate patterns of practice in palliative radiotherapy in Africa.
      MATERIALS AND METHODS: Fifteen centres in Africa provided detailed information
      about radiotherapy in both metastatic and locally advanced disease via a
      questionnaire. Information included general information (institution status,
      equipment, staff, patient number), radiotherapy and other treatment
      characteristics in bone metastasis, brain metastasis, metastatic spinal cord
      compression, lung and liver metastasis, as well as locally advanced tumours.
      RESULTS: The number of patients annually seen/treated ranged from 285 to 5000.
      Breast, cervix, head and neck, gastrointestinal and prostate cancer were the top
      five cancers overall. Eight (53%) institutions were without linear accelerators,
      four (27%) had a single one, whereas one institution each had two, three and four
      linear accelerators. The number of cobalt machines ranged from 0 to 2 (median 1).
      Most centres still prefer to use fractionated radiotherapy regimens over single
      fraction regimens in bone metastasis, although most centres are now using single
      fraction radiotherapy in retreatments. Radiotherapy in brain metastasis and
      metastatic spinal cord compression mostly conform to worldwide standards. Lung
      and liver metastases are rarely irradiated, largely as a consequence of the lack
      of modern radiotherapy technology. Locally advanced disease in various tumour
      sites was mostly palliated, in agreement with current evidence-based practices.
      CONCLUSIONS: African countries still lack adequate staffing and equipment to
      adequately address their clinical burden, being palliative in most cases.
      Emphasis should also be made on more rationally using existing capacities by
      using more of the single-fraction radiotherapy regimens, especially in bone
      metastasis.

PMID- 24746748
TI  - Maternal and affective behaviors of lactating rats reared in overlapping litters.
AB  - Postpartum mating in rats gives rise to complex family units consisting of the
      mother and two overlapping litters. As a consequence, newborn pups of the second
      litter, since the moment they are born, acquire experience not only from
      interaction with the mother and age-matched littermates but also from interaction
      with older siblings. Newborn pups reared in overlapping litters (OLs) receive a
      different pattern of maternal stimulation compared to those reared in single
      litters (SL: one litter of same aged pups), as the mothers reduce some maternal
      behavior components and juvenile pups from the first litter develop maternal
      behavior. Since there is strong evidence showing that variations in maternal
      behavior are transmitted throughout generations, we hypothesized that the altered
      pattern of maternal stimulation received by OL reared females would modify their
      behavior during motherhood. To test this hypothesis maternal behavior, maternal
      aggression and experimental anxiety of dams reared under OL and SL conditions
      during the first postpartum week were compared. No differences were found between
      the groups in their maternal behavior and aggression. This result may be
      explained by the maternal behavior of the juveniles that could compensate for the
      deficits in the caregiving behaviors received by OL litters. However, a subtle
      temporal reorganization of the licking behavior was found in OL reared mothers,
      together with an increased anxiety-related behavior in the plus maze test. These
      results suggest dissociation in the effects provoked by early environmental
      alterations on different behavioral systems, and more importantly, that
      independently of their early family composition, both groups can cope effectively
      with the changing demands of the pups. 

PMID- 24746750
TI  - Immunomodulatory effects by oral contraceptives in normal and cholestatic female
      rats: role of cytokines.
AB  - Oral contraceptives (OC) may cause intrahepatic cholestasis or increase a pre
      established liver damage. OC effects on hepatic injury biochemical markers remain
      contradictory and the role of cytokines in those processes is fairly unknown. Two
      doses, simple or double, of the OC combination ethinylestradiol/norgestrel were
      administered during 14 or 28 days to normal and cholestatic female rats. Liver
      damage markers and the cytokines tumor necrosis factor-alpha (TNF-alpha),
      interleukin-10 (IL-10) and transforming growth factor-beta (TGF-beta) were
      determined in plasma and liver. OC caused ambiguous results on cholestasis
      indicators, even more in cholestatic rats. Necrosis rose during cholestasis while
      OC lowered it in normal rats. Fibrosis was induced by cholestasis but OC double
      dose or intake time diminished that. Cholestasis depleted glycogen while OC did
      not alter it. Double dose or time of administration of OC significantly elevated
      the lipid peroxidation. Cholestasis modified plasma and liver cytokines but OC
      remarkably altered them in normal and cholestatic animals. TNF-alpha as well as
      IL-10 were increased in both tissues by OC, such rise was higher in normal rats.
      TGF-beta was augmented by OC and more in cholestatic rats receiving double dose.
      Thus, OC modified most liver injury markers in normal rats although more
      pronouncedly in cholestatic ones, as well as increased hepatic oxidative stress.
      Liver fibrosis was decreased and corroborated by histological analysis even when
      TGF-beta is elevated by OC. OC strongly immunomodulate cytokines that mediate
      liver damage or worsen a prior hepatopathy; those processes are influenced by
      dose, administration time and OC formulation.

PMID- 24746749
TI  - Inhibition of JNK and p38 MAPK phosphorylation by 5-(acetylamino)-4-oxo-6-phenyl
      2-hexenoic acid methyl ester and 4-phenyl-butenoic acid decreases substance P
      induced TNF-alpha upregulation in macrophages.
AB  - The interactions between the immune and nervous systems play an important role in
      immune and inflammatory conditions. Substance P (SP), the undecapeptide
      RPKPQQFFGLM-NH2, is known to upregulate the production of pro-inflammatory
      cytokines such as tumor necrosis factor (TNF)-alpha. We report here that 5
      (acetylamino)-4-oxo-6-phenyl-2-hexenoic acid methyl ester (AOPHA-Me) and 4-phenyl
      3-butenoic acid (PBA), two anti-inflammatory compounds developed in our
      laboratory, reduce SP-stimulated TNF-alpha expression in RAW 264.7 macrophages.
      We also show that AOPHA-Me and PBA both inhibit SP-stimulated phosphorylation of
      JNK and p38 MAPK. Furthermore, molecular modeling studies indicate that both
      AOPHA-Me and PBA dock at the ATP binding site of apoptosis signal-regulating
      kinase 1 (ASK1), a member of the MAPKs upstream of both JNK and p38 MAPK, with
      predicted interaction energies of -7.0 kcal/mol and -5.9 kcal/mol, respectively;
      this binding overlaps with that of staurosporine, a known inhibitor of ASK1.
      Taken together, these findings suggest that AOPHA-Me and PBA inhibition of TNF
      alpha expression in SP-stimulated RAW 264.7 macrophages is a consequence of the
      inhibition of JNK and p38 MAPK phosphorylation. We have previously shown that
      AOPHA-Me and PBA inhibit the amidative bioactivation of SP, which also would be
      expected to decrease formation of pro-inflammatory cytokines. It is conceivable
      that this dual action of inhibiting amidation and MAPK phosphorylation may be of
      some advantage in enhancing the anti-inflammatory activity of a therapeutic
      molecule.

PMID- 24746751
TI  - Intranasal curcumin attenuates airway remodeling in murine model of chronic
      asthma.
AB  - Curcumin, phytochemical present in turmeric, rhizome of Curcuma longa, a known
      anti-inflammatory molecule with variety of pharmacological activities is found
      effective in murine model of chronic asthma characterized by structural
      alterations and airway remodeling. Here, we have investigated the effects of
      intranasal curcumin in chronic asthma where animals were exposed to allergen for
      longer time. In the present study Balb/c mice were sensitized by an
      intraperitoneal injection of ovalbumin (OVA) and subsequently challenged with 2%
      OVA in aerosol twice a week for five consecutive weeks. Intranasal curcumin
      (5mg/kg) was administered from days 21 to 55, an hour before every nebulization
      and inflammatory cells recruitment, levels of IgE, EPO, IL-4 and IL-5 were found
      suppressed in bronchoalveolar lavage fluid (BALF). Intranasal curcumin
      administration prevented accumulation of inflammatory cells to the airways,
      structural alterations and remodeling associated with chronic asthma like
      peribronchial and airway smooth muscle thickening, sloughing off of the
      epithelial lining and mucus secretion in ovalbumin induced murine model of
      chronic asthma. 

PMID- 24746752
TI  - Assessing the validity of the RAND negative impact of asthma on quality of life
      short forms.
AB  - BACKGROUND: In response to recommendations from the 2010 National Institutes of
      Health Asthma Outcomes Workshop, we developed a system for measuring the negative
      impact of asthma on quality of life (QoL), which was referred to as the RAND
      Negative Impact of Asthma on Quality of Life (RAND-IAQL) item bank. The bank
      contains 65 items that focus on the patient's perception of the impact or bother
      of asthma on his or her life. OBJECTIVE: Evidence for the validity of 2 short
      forms, the RAND-IAQL 4-item and 12-item Short Forms, from the bank is presented.
      METHODS: Using a sample of 2032 adults with asthma, we validated our short forms
      against the Asthma Quality of Life Questionnaire-Marks (AQLQ-M), the Asthma
      Control Test, and generic measures of QoL developed by the Patient-reported
      Outcomes Measurement Information System (PROMIS). Discriminant validity was
      examined by comparing scores of respondents who differed according to multiple
      health indicators. RESULTS: Our sample ranged in age from 18 to 99 years (mean,
      43 years), with 14% Hispanic, 11% Asian, 19% African American, and 56% non
      Hispanic white race/ethnicity. Men had a significantly worse impact of asthma on
      QoL than women. The impact of asthma on QoL was greatest in African American and
      Hispanic subjects compared with that seen in non-Hispanic white subjects. Our
      measures correlated highly with the AQLQ-M and more strongly with the PROMIS
      global physical than mental scales. They differentiated between adults with
      asthma according to their perceived severity, level of control, presence or
      absence of exacerbations, and physical comorbidity. CONCLUSION: The RAND-IAQL
      item bank, measuring the impact of asthma on QoL, will complement other patient
      reported outcomes, such as measures of asthma symptoms, functioning, and control.

PMID- 24746753
TI  - Early-onset inflammatory bowel disease and common variable immunodeficiency-like
      disease caused by IL-21 deficiency.
AB  - BACKGROUND: Alterations of immune homeostasis in the gut can result in
      development of inflammatory bowel disease (IBD). Recently, Mendelian forms of IBD
      have been discovered, as exemplified by deficiency of IL-10 or its receptor
      subunits. In addition, other types of primary immunodeficiency disorders might be
      associated with intestinal inflammation as one of their leading clinical
      presentations. OBJECTIVE: We investigated a large consanguineous family with 3
      children who presented with early-onset IBD within the first year of life,
      leading to death in infancy in 2 of them. METHODS: Homozygosity mapping combined
      with exome sequencing was performed to identify the molecular cause of the
      disorder. Functional experiments were performed to assess the effect of IL-21 on
      the immune system. RESULTS: A homozygous mutation in IL21 was discovered that
      showed perfect segregation with the disease. Deficiency of IL-21 resulted in
      reduced numbers of circulating CD19(+) B cells, including IgM(+) naive and class
      switched IgG memory B cells, with a concomitant increase in transitional B-cell
      numbers. In vitro assays demonstrated that mutant IL-21(Leu49Pro) did not induce
      signal transducer and activator of transcription 3 phosphorylation and
      immunoglobulin class-switch recombination. CONCLUSION: Our study uncovers IL-21
      deficiency as a novel cause of early-onset IBD in human subjects accompanied by
      defects in B-cell development similar to those found in patients with common
      variable immunodeficiency. IBD might mask an underlying primary immunodeficiency,
      as illustrated here with IL-21 deficiency.

PMID- 24746754
TI  - Lung expression quantitative trait loci data set identifies important functional
      polymorphisms in the asthma-associated IL1RL1 region.

PMID- 24746755
TI  - Effect of gravity on volume of placental transfusion: a multicentre, randomised,
      non-inferiority trial.
AB  - BACKGROUND: Delayed cord clamping allows for the passage of blood from the
      placenta to the baby and reduces the risk of iron deficiency in infancy. To hold
      the infant for more than 1 min at the level of the vagina (as is presently
      recommended), on the assumption that gravity affects the volume of placental
      transfusion, is cumbersome, might result in low compliance, and interferes with
      immediate contact of the infant with the mother. We aimed to assess whether
      gravity affects the volume of placental transfusion METHODS: We did a multicentre
      non-inferiority trial at three university-affiliated hospitals in Argentina. We
      obtained informed consent from healthy mothers with normal term pregnancies
      admitted early in labour. Vigorous babies born vaginally were randomly assigned
      in a 1:1 ratio by computer-generated blocks and sequentially numbered sealed
      opaque envelopes to be held for 2 min before clamping the umbilical cord, at the
      level of the vagina (introitus group) or on the mother's abdomen or chest
      (abdomen group). Newborn babies were weighed immediately after birth and after
      cord clamping. The primary outcome was the difference in weight (as a proxy of
      placental transfusion volume). The prespecified non-inferiority margin was 18 g
      (20%). We used t test and chi(2) test for group comparison, and used a
      multivariable linear regression analysis to control for covariables. This trial
      is registered with ClinicalTrials.gov, number NCT01497353. FINDINGS: Between Aug
      1, 2011, and Aug 31, 2012, we allocated 274 newborn babies to the introitus group
      and 272 to the abdomen group. 77 newborn babies in the introitus group and 78 in
      the abdomen group were ineligible after randomisation (eg, caesarean section,
      forceps delivery, short umbilical cord or nuchal cord). Mean weight change was 56
      g (SD 47, 95% CI 50-63) for 197 babies in the introitus group compared with 53 g
      (45, 46-59) for 194 babies in the abdomen group, supporting non-inferiority of
      the two approaches (difference 3 g, 95% CI -5.8 to 12.8; p=0.45). We did not note
      any serious adverse events during the study. INTERPRETATION: Position of the
      newborn baby before cord clamping does not seem to affect volume of placental
      transfusion. Mothers could safely be allowed to hold their baby on their abdomen
      or chest. This change in practice might increase obstetric compliance with the
      procedure, enhance maternal-infant bonding, and decrease iron deficiency in
      infancy. FUNDING: Foundation for Maternal and Child Health (FUNDASAMIN).

PMID- 24746756
TI  - Delayed cord clamping: does gravity matter?

PMID- 24746757
TI  - Exploring cultural beliefs about "that sickness": grandmothers' explanations of
      HIV in an urban South African context.
AB  - The role of culture in community beliefs about HIV is important to understand,
      given poor adherence to treatment and the failure of prevention programs in some
      contexts. An exploration of such models may yield important insight into barriers
      to care, treatment-seeking paths, and intergenerational differences in cultural
      beliefs and practices. Our study aimed to understand South African grandmothers'
      traditional beliefs about HIV. Three focus groups were conducted with 15
      grandmothers from different cultural backgrounds in an urban community. Results
      indicated a variety of cultural explanations for causes, treatments, and
      prevention strategies. The lack of coherence and fluidity in opinions in this
      group suggests ways in which grandmothers may have a bridging role in the clinic
      that may help to validate and alleviate uncertainty, harmonize the voices of
      medicine and the lifeworld, and provide greater insight into people's ideas about
      health and treatment seeking, also known as the healthworld. 

PMID- 24746760
TI  - Chronic ossified subperiosteal hematoma of the iliac bone.

PMID- 24746759
TI  - Blunt splenic injury: outcomes of proximal versus distal and combined splenic
      artery embolization.
AB  - PURPOSE: To assess clinical outcomes of blunt splenic injuries (BSI) managed with
      proximal versus distal versus combined splenic artery embolization (SAE).
      MATERIALS AND METHODS: All consecutive patients with BSI admitted to our trauma
      centre from 2005 to 2010 and managed with SAE were reviewed. Outcomes were
      compared between proximal (P), distal (D) or combined (C) embolization. We
      focused on embolization failure (splenectomy), every adverse events occurring
      during follow up and material used for embolization. RESULTS: Fifty patients were
      reviewed (P n = 18, 36%; D n = 22, 44%; C n = 8, 16%). Mean injury severity score
      was 20. The technical success rate was 98%. Four patients required splenectomy (P
      n = 1, D n = 3, C n = 0). Clinical success rate for haemostasis was 92% (4 re
      bleeds: P n = 2, D n = 2, C n = 0). Outcomes were not statistically different
      between the materials used. Adverse events occurred in 65% of the patients during
      follow up. Four percent of the patients developed major complications and 56%
      developed minor complications attributable to embolization. There was no
      significant difference between the 3 groups. CONCLUSION: SAE had an excellent
      success rate with adverse events occurring in 65% of the patients and no
      significant differences found between the embolization techniques used. Proximal
      preventive embolization appears to protect in high-grade traumatic injuries.

PMID- 24746758
TI  - SOX2 expression is an early event in a murine model of EGFR mutant lung cancer
      and promotes proliferation of a subset of EGFR mutant lung adenocarcinoma cell
      lines.
AB  - OBJECTIVES: Primary and acquired resistance to EGFR TKIs in EGFR mutant lung
      cancer occurs primarily through secondary mutations in EGFR or Met amplification.
      Drug resistance can also be mediated by expression of pluripotency transcription
      factors, such as OCT4, SOX2 and NANOG that decrease terminal differentiation. In
      this study, we investigated the expression and role of SOX2 in model systems of
      EGFR mutant tumors. MATERIALS AND METHODS: Immunoblotting or immunohistochemistry
      was used to assess expression of pluripotency transcription factors in lungs of
      transgenic mice or in human NSCLC cell lines. Expression of SOX2 was reduced by
      shRNA knockdown, and response to erlotinib and cellular proliferation were
      assessed. RESULTS AND CONCLUSION: Induction of mutant EGFR in transgenic CCSP
      rtTA/TetO-EGFR(L858R/T790M) mice correlated with increased OCT4 and SOX2
      expression in lung tissue prior to tumor development. Established lung tumors
      retained SOX2 expression. To assess a role for SOX2 in tumorigenesis, a panel of
      NSCLC cell lines with activating EGFR mutations was assessed for SOX2 expression.
      Two of six cell lines with mutant EGFR showed detectable SOX2 levels, suggesting
      SOX2 expression did not correlate with EGFR mutation status. To assess the role
      of SOX2 in these cell lines, HCC827 and H1975 cells were infected with lentivirus
      containing SOX2 shRNA. Knockdown of SOX2 decreased proliferation in both cell
      lines and increased sensitivity to erlotinib in HCC827 cells. Because
      constitutive activation of the PI3K/Akt pathway is associated with EGFR TKI
      resistance, cells were treated with PI3K/AKT inhibitors and expression of SOX2
      was examined. PI3K/Akt inhibitors decreased SOX2 expression in a time-dependent
      manner. These data suggest targeting SOX2 may provide therapeutic benefit in the
      subset of EGFR-mutant tumors with high constitutive levels of SOX2, and that
      until more direct means of inhibiting SOX2 are developed, PI3K/Akt inhibitors
      might be useful to inhibit SOX2 in EGFR TKI resistant tumors.

PMID- 24746761
TI  - Current role of transcatheter arterial embolization for bladder and prostate
      hemorrhage.
AB  - Intractable hematuria from the bladder or the prostate can be life-threatening
      and its management remains a difficult clinical problem. Severe bleeding can
      arise as a result of radiation cystitis, bladder carcinoma, cyclophosphamide
      induced cystitis, severe infection, transurethral resection of the prostate and
      prostate cancer. When irrigation of the bladder through a three-way catheter and
      fulguration of the bleeding lesions fail to stop the hematuria, a life
      threatening situation can develop, when blood transfusion fails to keep pace with
      the rate of blood loss. Patients with massive uncontrollable hematuria are often
      elderly and unfit for cystectomy as a treatment. Many urologists have had to
      manage this difficult problem, and several different treatments have been
      attempted and described, with varying degrees of success. Transcatheter arterial
      embolization of the vesical or prostatic arteries is occasionally indicated in
      these patients when all other measures have failed. There is limited published
      experience with this procedure, but success in 90% of patients is reported when
      the vesical or prostatic arteries can be identified. The aim of this review is to
      describe the current place of transcatheter arterial embolization in the
      management of severe bladder or prostate bleeding after failed conservative
      therapy, and to review its efficacy and morbidity.

PMID- 24746762
TI  - [Crisis and the independence of public health policies. SESPAS report 2014].
AB  - Independence in the formulation of public health policies can be affected by
      various agents with objectives contrary to population health, such as large
      corporations. This lack of independence may be exacerbated by the economic crisis
      due to lower funding for health regulatory bodies or other measures designed to
      protect health. Large corporations have influenced the formulation of certain
      policies with an impact on health, such as those related to the tobacco industry,
      the chemical industry, nutrition, alcohol, pharmaceuticals, and health
      technology. The main areas in which these companies can influence policies are
      science, education, politics, and society in general. In this scenario, public
      health associations should take an active role in ensuring the independence of
      political decisions via actions such as the following: supporting strategies that
      guarantee the independence of public health policies and apply criteria of
      impartiality and transparency; rejecting those public-private partnerships
      launched to prevent health problems partly caused by these corporations;
      establishing partnerships to achieve independent training of health professionals
      and an institution with scientific authority in order to improve public health
      communication and counteract the lack of sound public health information;
      promoting a critical analysis of the definition of health problems and their
      solutions, and establishing related agendas (scientific, political and media) and
      alliances, so that continuing training for health professionals is independent. 

PMID- 24746763
TI  - [Assessment of the response following stereotactic irradiation of lung primary
      tumors and metastases].
AB  - Stereotactic radiotherapy is a standard treatment option for patients with stage
      I non-small cell lung cancer who are unfit for surgery or who are medically
      operable but refuse surgery. Comparable overall survival rates in operable
      patients are also supported by non-randomized single-institution and population
      based studies. Stereotactic radiotherapy has emerged as an alternative, effective
      and well tolerated in treating pulmonary oligometastases. The early detection of
      recurrence is important in the medically operable population for whom curative
      surgical salvage treatments are still available. A standardized definition of
      recurrence criteria becomes especially important in that context. In 2012, Huang
      et al. proposed a follow-up algorithm for these patients, whose different points
      are discussed in this publication.

PMID- 24746764
TI  - Reference values and universal screening of thyroid dysfunction in pregnant
      women.

PMID- 24746765
TI  - Historical figures at the office of Endocrinology.
AB  - Some historical figures have suffered endocrine diseases. This review relates
      those whose diseases have been published in the scientific literature. It takes a
      biographical summary and describes the disease process in those considered most
      relevant by the nature of the disease or the importance of the figure in the
      Spanish and Latin American context: the Pharaoh Akhenaten, Maximinus I,
      Bodhidharma, Sancho I of Leon, William the Conqueror, Enrique IV of Castile,
      Henry VIII, Mary Tudor, Carlos II of Spain, Pio Pico, Pedro II of Brazil,
      Eisenhower and J. F. Kennedy. 

PMID- 24746766
TI  - [Methicillin resistant Staphylococcus aureus isolated from mothers and children
      hospitalized in an Algiers hospital: predominance of the European virulent
      clone].

PMID- 24746767
TI  - Boosting accumulation of neutral lipids in Rhodosporidium kratochvilovae HIMPA1
      grown on hemp (Cannabis sativa Linn) seed aqueous extract as feedstock for
      biodiesel production.
AB  - Hemp seeds aqueous extract (HSAE) was used as cheap renewable feedstocks to grow
      novel oleaginous yeast Rhodosporidium kratochvilovae HIMPA1 isolated from
      Himalayan permafrost soil. The yeast showed boosted triglyceride (TAG)
      accumulation in the lipid droplets (LDs) which were transesterified to biodiesel.
      The sonicated HSAE prepared lacked toxic inhibitors and showed enhanced total
      lipid content and lipid yield 55.56%, 8.39+/-0.57g/l in comparison to 41.92%,
      6.2+/-0.8g/l from industrially used glucose synthetic medium, respectively.
      Supersized LDs (5.95+/-1.02MUm) accumulated maximum TAG in sonicated HSAE grown
      cells were visualized by fluorescent BODIPY (505/515nm) stain. GC-MS analysis
      revealed unique longer carbon chain FAME profile containing Arachidic acid
      (C20:0) 5%, Behenic acid (C22:0) 9.7%, Heptacosanoic acid (C27:0) 14.98%, for the
      first time in this yeast when grown on industrially competent sonicated HSAE,
      showing more similarity to algal oils. 

PMID- 24746768
TI  - Scale-up of osmotic membrane bioreactors by modeling salt accumulation and draw
      solution dilution using hollow-fiber membrane characteristics and operation
      conditions.
AB  - A full-scale osmotic membrane bioreactor (OMBR) model was developed to simulate
      salt accumulation, draw solution (DS) dilution, and water flux over the hollow
      fiber membrane length. The model uses the OMBR design parameters, DS properties,
      and forward osmosis (FO) membrane characteristics obtained from lab-scale tests.
      The modeling results revealed a tremendous water flux decline (10->0.82LMH) and
      short solids retention time (SRT: 5days) due to salt accumulation and DS dilution
      when OMBR is scaled up using commercially available DS and FO membrane. Simulated
      water flux is a result of interplay among reverse salt flux, internal and
      external concentration polarization (ICP and ECP). ECP adversely impacts water
      flux considerably in full-scale OMBR although it is often ignored in previous
      works. The OMBR model makes it possible to select better DS properties (higher
      flow rate and salt concentration) and FO membranes with higher water flux
      propensity in full-scale operation. 

PMID- 24746769
TI  - Development of a microbial process for the recovery of petroleum oil from
      depleted reservoirs at 91-96 degrees C.
AB  - A consortium of bacteria growing at 91 degrees C and above (optimally at 96
      degrees C) was developed for the recovery of crude oil from declining/depleted
      oil reservoirs having temperature of more than 91 degrees C. PCR-DGGE-Sequencing
      analysis of 16S rRNA gene fragments of NJS-4 consortium revealed the presence of
      four strains identified as members of the genus Clostridium. The metabolites
      produced by NJS-4 consortium included volatile fatty acids, organic acids,
      surfactants, exopolysaccarides and CO2, which reduced viscosity, emulsified crude
      oil and increased the pressure that facilitated displacement of emulsified oil
      towards the surface. NJS-4 enhanced oil recovery by 26.7% and 10.1% in sand pack
      trials and core flood studies respectively in optimized nutrient medium comprised
      of sucrose and sodium acetate as carbon/energy source and urea as nitrogen source
      (pH 7-9, 96 degrees C, and 4% salinity). Nutrient medium for MEOR was constituted
      using commercial grade cheap nutrients to improve the economic viability of MEOR
      process. 

PMID- 24746770
TI  - WITHDRAWN: Fate of extracellular polymeric substances during flocculation of
      anaerobically digested sludge using biogenic flocculant.
AB  - This article has been withdrawn at the request of the authors and 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- 24746771
TI  - Identification of uncoupling protein 4 from the blood-sucking insect Rhodnius
      prolixus and its possible role on protection against oxidative stress.
AB  - Uncoupling proteins (UCPs) play a critical role in the control of the
      mitochondrial membrane potential (DeltaPsim) due to their ability to dissipate
      the proton gradient, which results in the uncoupling of mitochondrial respiration
      from ATP production. Most reactive oxygen species generation in mitochondria
      occurs in complex III, due to an increase of semiquinone (Q(-)) half-life. When
      active, UCPs can account as a potential antioxidant system by decreasing
      DeltaPsim and increasing mitochondrial respiration, thus reducing Q(-) life time.
      The hematophagous insect Rhodnius prolixus, a vector of Chagas disease, is
      exposed to a huge increase in oxidative stress after a blood meal because of the
      hydrolysis of hemoglobin and the release of the cytotoxic heme molecule. Although
      some protective mechanisms were already described for this insect and other
      hematophagous arthropods, the putative role of UCP proteins as antioxidants in
      this context has not been explored. In this report, two genes encoding UCP
      proteins (RpUcp4 and RpUcp5) were identified in the R. prolixus genome. RpUcp4 is
      the predominant transcript in most analyzed organs, and both mRNA and protein
      expression are upregulated (13- and 3-fold increase, respectively) in enterocytes
      the first day after the blood feeding. The increase in UCP4 expression is
      coincident with the decrease in hydrogen peroxide (H2O2) generation by midgut
      cells. Furthermore, in mitochondria isolated from enterocytes, the modulation of
      UCP activity by palmitic acid and GDP resulted in altered DeltaPsim, as well as
      modulation of H2O2 generation rates. These results indicate that R. prolixus UCP4
      may function in an antioxidation mechanism to protect the midgut cells against
      oxidative damage caused by blood digestion. 

PMID- 24746772
TI  - Non conserved residues between Cqm1 and Aam1 mosquito alpha-glucosidases are
      critical for the capacity of Cqm1 to bind the Binary toxin from Lysinibacillus
      sphaericus.
AB  - The Binary (Bin) toxin from the entomopathogenic bacterium Lysinibacillus
      sphaericus acts on larvae of the culicid Culex quinquefasciatus through its
      binding to Cqm1, a midgut-bound alpha-glucosidase. Specific binding by the BinB
      subunit to the Cqm1 receptor is essential for toxicity however the toxin is
      unable to bind to the Cqm1 ortholog from the refractory species Aedes aegypti
      (Aam1). Here, to investigate the molecular basis for the interaction between Cqm1
      and BinB, recombinant Cqm1 and Aam1 were first expressed as soluble forms in Sf9
      cells. The two proteins were found to display the same glycosilation patterns and
      BinB binding properties as the native alpha-glucosidases. Chimeric constructs
      were then generated through the exchange of reciprocal fragments between the
      corresponding cqm1 and aam1 cDNAs. Subsequent expression and binding experiments
      defined a Cqm1 segment encompassing residues S129 and A312 as critical for the
      interaction with BinB. Through site directed mutagenesis experiments, replacing
      specific sets of residues from Cqm1 with those of Aam1, the 159GG160 doublet was
      required for this interaction. Molecular modeling mapped these residues to an
      exposed loop within the Cqm1's structure, compatible with a target site for BinB
      and providing a possible explanation for its lack of binding to Aam1. 

PMID- 24746773
TI  - Diet quality and body mass index are associated with health care resource use in
      rural older adults.
AB  - Health care resource consumption is a growing concern. The aim of this study was
      to examine the associations between diet quality and body mass index with health
      care resource use (HRU) in a cohort of advanced age. Participants in the
      Geisinger Rural Aging Study (n=5,993) were mailed demographic and dietary
      questionnaires in 2009. Of those eligible, 2,995 (50%; 1,267 male, 1,728 female;
      mean age 81.4+/-4.4 years) provided completed surveys. Multivariate negative
      binomial models were used to estimate relative risk and 95% CI of HRU outcomes
      with diet quality as assessed by the Dietary Screening Tool score and body mass
      index determined from self-reported height and weight. Poor diet quality was
      associated with a 20% increased risk for emergency room (ER) visits. Fruit and
      vegetable consumption was grouped into quintiles of intake, with the highest
      quintile serving as the reference group in analyses. The three lowest fruit and
      vegetable quintiles were associated with increased risk for ER visits (23% to
      31%); the lowest quintile increased risk for inpatient visits (27%). Obesity
      increased risk of outpatient visits; however, individuals with class I obesity
      were less likely than normal-weight individuals to have ER visits (relative
      risk=0.84; 95% CI 0.70 to 0.99). Diets of greater quality, particularly with
      greater fruit and vegetable intake, are associated with favorable effects on HRU
      outcomes among older adults. Overweight and obesity are associated with increased
      outpatient HRU and, among obese individuals, with decreased ER visits. These
      findings suggest that BMI and diet quality beyond age 74 years continue to affect
      HRU measures. 

PMID- 24746774
TI  - Generalized total variation-based MRI Rician denoising model with spatially
      adaptive regularization parameters.
AB  - Magnetic resonance imaging (MRI) is an outstanding medical imaging modality but
      the quality often suffers from noise pollution during image acquisition and
      transmission. The purpose of this study is to enhance image quality using feature
      preserving denoising method. In current literature, most existing MRI denoising
      methods did not simultaneously take the global image prior and local image
      features into account. The denoising method proposed in this paper is implemented
      based on an assumption of spatially varying Rician noise map. A two-step wavelet
      domain estimation method is developed to extract the noise map. Following a
      Bayesian modeling approach, a generalized total variation-based MRI denoising
      model is proposed based on global hyper-Laplacian prior and Rician noise
      assumption. The proposed model has the properties of backward diffusion in local
      normal directions and forward diffusion in local tangent directions. To further
      improve the denoising performance, a local variance estimator-based method is
      introduced to calculate the spatially adaptive regularization parameters related
      to local image features and spatially varying noise map. The main benefit of the
      proposed method is that it takes full advantage of the global MR image prior and
      local image features. Numerous experiments have been conducted on both synthetic
      and real MR data sets to compare our proposed model with some state-of-the-art
      denoising methods. The experimental results have demonstrated the superior
      performance of our proposed model in terms of quantitative and qualitative image
      quality evaluations. 

PMID- 24746775
TI  - Gradient induced artifacts in simultaneous EEG-fMRI: Effect of synchronization on
      spiral and EPI k-space trajectories.
AB  - The nature of the gradient induced electroencephalography (EEG) artifact is
      analyzed and compared for two functional magnetic resonance imaging (fMRI) pulse
      sequences with different k-space trajectories: echo planar imaging (EPI) and
      spiral. Furthermore, the performance of the average artifact subtraction
      algorithm (AAS) to remove the gradient artifact for both sequences is evaluated.
      The results show that the EEG gradient artifact for spiral sequences is one order
      of magnitude higher than for EPI sequences due to the chirping spectrum of the
      spiral sequence and the dB/dt of its crusher gradients. However, in the presence
      of accurate synchronization, the use of AAS yields the same artifact suppression
      efficiency for both pulse sequences below 80Hz. The quality of EEG signal after
      AAS is demonstrated for phantom and human data. EEG spectrogram and visual evoked
      potential (VEP) are compared outside the scanner and use both EPI and spiral
      pulse sequences. MR related artifact residues affect the spectra over 40Hz (less
      than 0.2 MUV up to 120Hz) and modify the amplitude of P1, N2 and P300 in the VEP.
      These modifications in the EEG signal have to be taken into account when
      interpreting EEG data acquired in simultaneous EEG-fMRI experiments. 

PMID- 24746776
TI  - Effect of smoking on Tp-e interval, Tp-e/QT and Tp-e/QTc ratios as indices of
      ventricular arrhythmogenesis.
AB  - BACKGROUND: Smoking may lead to ventricular arrhythmias and sudden cardiac death
      via altering ventricular recovery time dispersion indices such as QT interval and
      QT dispersion (QTd). The Tp-e/QT and Tp-e/QTc ratios are also known as predictors
      of ventricular arrhythmogenesis. The aim of this study was to evaluate the
      relationship between cigarette smoking and ventricular repolarisation dispersion
      using these novel electrocardiographic parameters. METHODS: One hundred and
      twenty-one chronic smokers and 70 age- and sex-matched non-smoker controls were
      included in our study. The Tp-e interval and Tp-e/QT ratio were measured by 12
      lead electrocardiogram, and corrected for heart rate. RESULTS: QTd (34.2 +/- 8.4,
      27.2 +/- 10.4, P<0.001) and corrected QTd (37.3 +/- 8.9, 29.8 +/- 11.2, P<0.001)
      were significantly increased in the smokers compared to the non-smoker control
      group. The Tp-e interval (76.5 +/- 6.3, 70.3 +/- 6.8, P<0.001), cTp-e interval
      (83.5 +/- 8.0, 77.1 +/- 8.7, P<0.001), Tp-e/QT (0.20 +/- 0.03, 0.19 +/- 0.02,
      P<0.001) and Tp-e/QTc ratios (0.19 +/- 0.02, 0.17 +/- 0.02, P<0.001) were
      increased in the patient group when compared to the controls. Significant
      positive correlations were also found between the level of smoking with the cTp-e
      interval (r=0.836, P<0.001), and Tp-e/QT (r=0.714, P<0.001) and Tp-e/QTc ratios
      (r=0.448, P<0.001). CONCLUSION: We found in our study that cTp-e interval, Tp
      e/QT and Tp-e/QTc ratios were increased in smokers and significantly correlated
      to the amount of smoking.

PMID- 24746777
TI  - Fatal left ventricular free wall rupture following acute myocardial infarction.

PMID- 24746778
TI  - Organ dysfunction in patients with left ventricular impairment: what is the
      effect of cardiopulmonary bypass?
AB  - OBJECTIVE: We have previously demonstrated that avoidance of cardiopulmonary
      bypass may reduce early mortality and cardiac related complications in patients
      with left ventricular dysfunction. This study examines the impact of
      cardiopulmonary bypass in the same subgroup in terms of organ dysfunction and non
      cardiac related complications METHODS: A systematic literature review identified
      24 studies including 7,976 patients. Data was extracted for the following
      outcomes of interest: stroke, renal failure, ventilation time, pulmonary
      complications and sternal wound infection. Random effects meta-analysis was used
      to aggregate the data. Sensitivity and heterogeneity were assessed. RESULTS: Meta
      analysis through subgroup analysis of the highest quality studies revealed that
      the off-pump technique is associated with significantly lower incidence of
      stroke, renal failure, ventilation time and sternal wound infection. CONCLUSION:
      These results highlight an important link between cardiopulmonary bypass and the
      incidence of multi-organ dysfunction in patients with left ventricular
      dysfunction. The results add to the growing body of evidence that off-pump
      surgery is more beneficial in high-risk patients. Even in the light of mixed
      reports on graft patency and completeness of revascularisation, the technique may
      be justified in selected patients in attempt to reduce organ dysfunction.

PMID- 24746779
TI  - Anthelmintic efficacy on UK Thoroughbred stud farms.
AB  - Anthelmintic drugs have been applied indiscriminately to control horse nematodes
      for over 40 years. We undertook a comprehensive study to investigate efficacy of
      the four available broad-spectrum anthelmintic drugs on 16 Thoroughbred stud
      farms using the faecal egg count reduction test. Efficacy against strongyles was
      determined by calculating the percentage of reduction in faecal egg count between
      the group mean at Day 0 and Days 14-17 post-treatment and the 95% lower
      confidence intervals estimated by non-parametric bootstrapping. Individual
      strongyle faecal egg count reduction tests (n=429) were performed in which 179,
      131, 89 and 30 horses were administered ivermectin, moxidectin, pyrantel and
      fenbendazole, respectively. Moxidectin was efficacious in all tests (faecal egg
      count reduction range: 99.8-100%; 95% lower confidence intervals range: 96.8
      100%) and reduced efficacy of ivermectin (faecal egg count reduction range: 85.7
      100%; 95% lower confidence intervals range: 65-100%) was observed in one group of
      yearlings. Reduced pyrantel efficacy was observed in five groups of yearlings
      (faecal egg count reduction range: 0-73%; 95% lower confidence intervals range: 0
      59.5%), but pyrantel was found to be efficacious when administered to mares
      (faecal egg count reduction range: 98-99.4%; 95% lower confidence intervals
      range: 91.8-99.3%). Low efficacy of fenbendazole was always observed (faecal egg
      count reduction range: 0.4-41%; 95% lower confidence intervals not calculable).
      Two further methods for estimating efficacy were applied and outputs obtained
      using all methodologies were in agreement. Efficacy against Parascaris equorum
      was assessed on four farms: fenbendazole had acceptable efficacy (faecal egg
      count reduction range: 97.5-99.9%; 95% lower confidence intervals range: 96.3
      99.1%), but reduced efficacy of ivermectin was observed (faecal egg count
      reduction range: 25.5-91.2%; 95% lower confidence intervals range: 6.7-82.4%).
      Strongyle faecal egg count were analysed at approximately 2 week intervals for up
      to 12 weeks after anthelmintic drug administration to determine the egg
      reappearance period for moxidectin, ivermectin and pyrantel. The egg reappearance
      period for all three anthelmintic drugs was shorter than previously observed.
      Overall, our results indicate that ivermectin and moxidectin administration
      provided acceptable efficacy at 14 days; however, egg reappearance period results
      suggest that these products are working less effectively than measured
      previously. As shortened egg reappearance period is believed to be an early
      indicator of resistance, this highlights the issue of impending multi-drug
      resistance in strongyles on stud farms.

PMID- 24746780
TI  - BMI and levels of zinc, copper in hair, serum and urine of Turkish male patients
      with androgenetic alopecia.
AB  - OBJECTIVE: Male pattern androgenetic alopecia is characterized by progressive
      hair loss from the scalp. It is known that imbalances of some trace elements play
      a role in the pathomechanism of many forms of alopecia. The aim of this study was
      to evaluate the levels of zinc and copper in hair, serum and urine samples of
      Turkish males with male pattern androgenetic alopecia and to compare with healthy
      controls. MATERIAL AND METHODS: 116 males with male pattern androgenetic alopecia
      and 100 controls were involved in this study. RESULTS: Levels of zinc and copper
      in hair were decreased significantly in the patients (p<0.05), although zinc and
      copper levels of serum and urine were not different between patients and controls
      (p>0.05). Body mass index of patients were higher than control group. In
      addition, in the group with body mass index of 25 and lower zinc level in hair
      and urine, copper level in serum were significantly higher (p<0.05). Body mass
      index was negatively correlated with hair zinc levels. CONCLUSION: We thought
      that decreased zinc and copper levels in hair may play a role in the etiology of
      male pattern androgenetic alopecia. In addition, obesity by making changes in the
      balance of the trace elements in hair, serum and urine may play a role in male
      pattern androgenetic alopecia. Hence, assessing the levels of trace elements in
      hair of male pattern androgenetic alopecia patients may be more valuable compared
      to serum and urine for treatment planning.

PMID- 24746781
TI  - Future resuscitation guidelines should contain more specific recommendations
      regarding simulation-based training.

PMID- 24746782
TI  - Failure to perceive clinical events: an under-recognised source of error.
AB  - INTRODUCTION: Attentional focus narrows as individuals concentrate on tasks.
      Missing an event that would otherwise appear obvious is termed a perceptual
      error. These forms of perceptual failure are well-recognised in psychological
      literature, but little attention has been paid to them in medicine. Cognitive
      workload and expertise modulate risk, although how these factors interplay in
      practice is unclear. This video-based experiment was designed to explore the
      hypothesis that perceptual errors affect clinicians. METHODS: 142 volunteers with
      varying levels of experience of adult resuscitation were shown a short video
      depicting a simulated cardiac arrest. This video included a series of change
      events designed to elicit perceptual errors. The experiment was conducted on
      line, with participants watching the video and then responding via combinations
      of open-ended free-text and directed questioning. RESULTS: 141 people experienced
      at least a single perceptual error. Even the most clinically significant event
      (disconnection of the patient's oxygen supply) was missed by three in four
      viewers. Although expertise was associated with increased likelihood of detecting
      an occurrence, even highly significant events were missed by up to two thirds of
      the most experienced observers. DISCUSSION: This study demonstrates, for the
      first time, that perceptual errors occur during healthcare-relevant scenarios at
      significant levels. Events such as an oxygen malfunction would meaningfully
      affect patient outcome and, although expertise conferred some advantages, events
      were still missed more often than not. Data acquisition is fundamental to good
      quality situational awareness. These results suggest perceptual error may be a
      contributor to adverse events in practice.

PMID- 24746783
TI  - Neurologic outcome in comatose patients resuscitated from out-of-hospital cardiac
      arrest with prolonged downtime and treated with therapeutic hypothermia.
AB  - BACKGROUND: Previous reports have shown that prolonged duration of resuscitation
      efforts in out-of-hospital cardiac arrest (OHCA) is associated with poor
      neurologic outcome. This concept has recently been questioned with advancements
      in post-cardiac arrest care including the use of therapeutic hypothermia (TH).
      The aim of this study was to determine the rate of good neurologic outcome based
      on the duration of resuscitation efforts in OHCA patients treated with TH.
      METHODS: This prospective, observational, study was conducted between January
      2008 and September 2012. Inclusion criteria consisted of adult non-traumatic OHCA
      patients who were comatose after return of spontaneous circulation (ROSC) and
      received TH. The primary endpoint was good neurologic outcome defined as a
      cerebral performance category score of 1 or 2. Downtime was calculated as the
      length of time between the patient being recognized as pulseless and ROSC.
      RESULTS: 105 patients were treated with TH and 19 were excluded due to unknown
      downtime, leaving 86 patients for analysis. The median downtime was 18.5 (10.0
      32.3)min and 33 patients (38.0%) had a good neurologic outcome. When downtime was
      divided into four groups (<=10min, 11-20min, 21-30min, >30min), good neurologic
      outcomes were 62.5%, 37%, 25%, and 21.7%, respectively (p=0.02). However, even
      with downtime >20min, 22.9% had a good neurologic outcome, and this percentage
      increased to 37.5% in patients with an initial shockable rhythm. CONCLUSIONS:
      Although longer downtime is associated with worse outcome in OHCA patients, we
      found that comatose patients who have been successfully resuscitated and treated
      with TH have neurologically intact survival rates of 23% even with downtime
      >20min.

PMID- 24746784
TI  - Pre-hospital management of anaphylaxis in one Canadian Urban Centre.
AB  - STUDY AIM: Anaphylaxis requires prompt recognition and management to improve
      patient outcomes. This study examined the diagnosis and treatment of anaphylactic
      reactions by the Emergency Medical Services (EMS) in a Canadian urban centre.
      METHODS: Electronic patient care records (ePCRs), identifying allergy-related
      calls in the Edmonton-Zone for the year 2011, were retrospectively reviewed to
      confirm anaphylaxis diagnosis and record treatments. Data were abstracted and
      entered into the REDCap electronic platform. Descriptive and multivariable
      analyses were performed. Pre-hospital management included any care provided by
      paramedic personnel and/or first-aid treatment received prior to EMS arrival.
      RESULTS: From 481 identified allergy-related case records, 136 (28%) met
      guideline criteria for anaphylaxis. Seventy-six (56%) of these confirmed cases
      were deemed high acuity by medical dispatchers. Self-medication and bystander
      first-aid was recorded in 60 (44%) anaphylactic events; 34 (25%) received
      epinephrine. Paramedics administered epinephrine in an additional 49 cases (36%);
      only 7% received all three primary pre-hospital anaphylaxis treatments:
      epinephrine, corticosteroids, and antihistamines. Factors associated with pre
      hospital epinephrine administration included: previous episode of anaphylaxis
      (adjusted odds ratio [aOR]=4.9, 95% confidence interval [CI]: 1.30, 19.21);
      administration of corticosteroids by bystanders or EMS personnel (aOR=3.8, 95%
      CI: 1.36, 10.65); and transport severity (aOR=3.2, 95% CI: 1.21, 8.36).
      CONCLUSION: Paramedics in this region demonstrated higher use of epinephrine than
      reported elsewhere; however, almost half of all patients meeting anaphylaxis
      criteria did not receive pre-hospital epinephrine. Instead, more patients
      received antihistamines. Efforts to improve adherence to anaphylaxis protocols
      and guidelines appear warranted.

PMID- 24746785
TI  - Incidence and outcome of in-hospital cardiac arrest in the United Kingdom
      National Cardiac Arrest Audit.
AB  - OBJECTIVE: To report the incidence, characteristics and outcome of adult in
      hospital cardiac arrest in the United Kingdom (UK) National Cardiac Arrest Audit
      database. METHODS: A prospectively defined analysis of the UK National Cardiac
      Arrest Audit (NCAA) database. 144 acute hospitals contributed data relating to
      22,628 patients aged 16 years or over receiving chest compressions and/or
      defibrillation and attended by a hospital-based resuscitation team in response to
      a 2222 call. The main outcome measures were incidence of adult in-hospital
      cardiac arrest and survival to hospital discharge. RESULTS: The overall incidence
      of adult in-hospital cardiac arrest was 1.6 per 1000 hospital admissions with a
      median across hospitals of 1.5 (interquartile range 1.2-2.2). Incidence varied
      seasonally, peaking in winter. Overall unadjusted survival to hospital discharge
      was 18.4%. The presenting rhythm was shockable (ventricular fibrillation or
      pulseless ventricular tachycardia) in 16.9% and non-shockable (asystole or
      pulseless electrical activity) in 72.3%; rates of survival to hospital discharge
      associated with these rhythms were 49.0% and 10.5%, respectively, but varied
      substantially across hospitals. CONCLUSIONS: These first results from the NCAA
      database describing the current incidence and outcome of adult in-hospital
      cardiac arrest in UK hospitals will serve as a benchmark from which to assess the
      future impact of changes in service delivery, organisation and treatment for in
      hospital cardiac arrest.

PMID- 24746786
TI  - C-reactive protein levels after cardiac arrest in patients treated with
      therapeutic hypothermia.
AB  - AIM: Prognostication of outcome after cardiac arrest (CA) is challenging. We
      assessed the prognostic value of daily blood levels of C-reactive protein (CRP),
      a cheap and widely available inflammatory biomarker, after CA. METHODS: We
      reviewed the data of all patients admitted to our intensive care unit (ICU) after
      CA between January 2009 and December 2011 and who survived for at least 24h. We
      collected demographic data, CA characteristics (initial rhythm; location of
      arrest; time to return of spontaneous circulation [ROSC]), occurrence of
      infection, ICU survival and neurological outcome at three months (good=cerebral
      performance category [CPC] 1-2; poor=CPC 3-5). CRP levels were measured daily
      from admission to day 3. RESULTS: A total of 130 patients were admitted after
      successful resuscitation from CA and survived more than 24h; 76 patients (58%)
      developed an infection and overall mortality was 56%. CRP levels increased from
      admission to day 3. CRP levels were higher in in-hospital than in out-of-hospital
      CA, especially on admission and day 1 (44.1 vs. 2.1 mgL(-1) and 74.5 vs. 29.5
      mgL(-1), respectively; p<0.001), and in patients with non-shockable than in those
      with shockable rhythms. In a logistic regression model, high CRP levels on
      admission were independently associated with poor neurological outcome at 3
      months. CONCLUSION: CRP levels increase in the days following successful
      resuscitation of CA. Higher CRP levels in patients with in-hospital CA, non
      shockable rhythms and infection, suggest a greater inflammatory response in these
      patients. High CRP levels on admission may identify patients at high-risk of poor
      outcome and could be a target for future therapies.

PMID- 24746787
TI  - Imagine what we will "know" tomorrow: the naked truth about cardiopulmonary
      resuscitation quality research.

PMID- 24746788
TI  - Automatic detection of chest compressions for the assessment of CPR-quality
      parameters.
AB  - AIM: Accurate chest compression detection is key to evaluate cardiopulmonary
      resuscitation (CPR) quality. Two automatic compression detectors were developed,
      for the compression depth (CD), and for the thoracic impedance (TI). The
      objective was to evaluate their accuracy for compression detection and for CPR
      quality assessment. METHODS: Compressions were manually annotated using the force
      and ECG in 38 out-of-hospital resuscitation episodes, comprising 869 min and
      67,402 compressions. Compressions were detected using a negative peak detector
      for the CD. For the TI, an adaptive peak detector based on the amplitude and
      duration of TI fluctuations was used. Chest compression rate (CC-rate) and chest
      compression fraction (CCF) were calculated for the episodes and for every minute
      within each episode. CC-rate for rescuer feedback was calculated every 8
      consecutive compressions. RESULTS: The sensitivity and positive predictive value
      were 98.4% and 99.8% using CD, and 94.2% and 97.4% using TI. The mean CCF and CC
      rate obtained from both detectors showed no significant differences with those
      obtained from the annotations (P>0.6). The Bland-Altman analysis showed
      acceptable 95% limits of agreement between the annotations and the detectors for
      the per-minute CCF, per-minute CC-rate, and CC-rate for feedback. For the
      detector based on TI, only 3.7% of CC-rate feedbacks had an error larger than 5%.
      CONCLUSION: Automatic compression detectors based on the CD and TI signals are
      very accurate. In most cases, episode review could safely rely on these detectors
      without resorting to manual review. Automatic feedback on rate can be accurately
      done using the impedance channel.

PMID- 24746789
TI  - New screening method to detect carriage of carbapenemase-producing
      Enterobacteriaceae in patients within 24 hours.
AB  - Rapid identification of patients colonized with carbapenemase-producing
      Enterobacteriaceae (CPE) is essential to prevent introduction and the spread of
      CPE in the hospital. This article presents the results of a new screening method
      to detect patients colonized with CPE within 24h after hospital admission. From
      high-risk patients rectal and throat swabs were collected and incubated
      overnight, after which DNA was isolated and tested for the most prevalent CPE
      genes (KPC, NDM, OXA-48, VIM and IMP) by a ligation-mediated real-time polymerase
      chain reaction. In 14 months 454 patients were screened; in six patients CPE were
      detected (carriage rate 1.3%). 

PMID- 24746790
TI  - Protection of SK-N-MC cells against beta-amyloid peptide-induced degeneration
      using neuron growth factor-loaded liposomes with surface lactoferrin.
AB  - A liposomal system with surface lactoferrin (Lf) was developed for delivering
      neuron growth factor (NGF) across the blood-brain barrier (BBB) and improving the
      viability of neuron-like SK-N-MC cells with deposited beta-amyloid peptide
      (Abeta). The Lf-grafted liposomes carrying NGF (Lf/NGF-liposomes) were applied to
      a monolayer of human brain-microvascular endothelial cells (HBMECs) regulated by
      human astrocytes (HAs) and to fibrillar Abeta1-42-insulted SK-N-MC cells. An
      increase in cholesterol mole percentage enhanced the particle size, absolute
      value of zeta potential, and physical stability, however, reduced the entrapment
      efficiency and release rate of NGF. In addition, an increase in Lf concentration
      increased the particle size, surface nitrogen percentage, NGF permeability across
      the BBB, and viability of HBMECs, HAs, and SK-N-MC cells, however, decreased the
      absolute value of zeta potential, surface phosphorus percentage, and loading
      efficiency of Lf. After treating with Lf/NGF-liposomes, a higher Abeta
      concentration yielded a lower survival of SK-N-MC cells. The current Lf/NGF
      liposomes are efficacious drug carriers to target the BBB and inhibit the Abeta
      induced neurotoxicity as potential pharmacotherapy for Alzheimer's disease. 

PMID- 24746791
TI  - Whole-brain imaging with single-cell resolution using chemical cocktails and
      computational analysis.
AB  - Systems-level identification and analysis of cellular circuits in the brain will
      require the development of whole-brain imaging with single-cell resolution. To
      this end, we performed comprehensive chemical screening to develop a whole-brain
      clearing and imaging method, termed CUBIC (clear, unobstructed brain imaging
      cocktails and computational analysis). CUBIC is a simple and efficient method
      involving the immersion of brain samples in chemical mixtures containing
      aminoalcohols, which enables rapid whole-brain imaging with single-photon
      excitation microscopy. CUBIC is applicable to multicolor imaging of fluorescent
      proteins or immunostained samples in adult brains and is scalable from a primate
      brain to subcellular structures. We also developed a whole-brain cell-nuclear
      counterstaining protocol and a computational image analysis pipeline that,
      together with CUBIC reagents, enable the visualization and quantification of
      neural activities induced by environmental stimulation. CUBIC enables time-course
      expression profiling of whole adult brains with single-cell resolution.

PMID- 24746792
TI  - FDG PET/MR for lymph node staging in head and neck cancer.
AB  - OBJECTIVE: To assess the diagnostic value of PET/MR (positron emission
      tomography/magnetic resonance imaging) with FDG (18F-fluorodeoxyglucose) for
      lymph node staging in head and neck cancer. MATERIALS AND METHODS: This
      prospective study was approved by the local ethics committee; all patients signed
      informed consent. Thirty-eight patients with squamous cell carcinoma of the head
      and neck region underwent a PET scan on a conventional scanner and a subsequent
      PET/MR on a whole-body hybrid system after a single intravenous injection of FDG.
      The accuracy of PET, MR and PET/MR for lymph node metastases were compared using
      receiver operating characteristic (ROC) analysis. Histology served as the
      reference standard. RESULTS: Metastatic disease was confirmed in 16 (42.1%) of 38
      patients and 38 (9.7%) of 391 dissected lymph node levels. There were no
      significant differences between PET/MR, MR and PET and MR (p>0.05) regarding
      accuracy for cervical metastatic disease. Based on lymph node levels, sensitivity
      and specificity for metastatic involvement were 65.8% and 97.2% for MR, 86.8% and
      97.0% for PET and 89.5% and 95.2% for PET/MR. CONCLUSIONS: In head and neck
      cancer, FDG PET/MR does not significantly improve accuracy for cervical lymph
      node metastases in comparison to MR or PET.

PMID- 24746793
TI  - Trim9 regulates activity-dependent fine-scale topography in Drosophila.
AB  - Topographic projection of afferent terminals into 2D maps in the CNS is a general
      strategy used by the nervous system to encode the locations of sensory stimuli.
      In vertebrates, it is known that although guidance cues are critical for
      establishing a coarse topographic map, neural activity directs fine-scale
      topography between adjacent afferent terminals [1-4]. However, the molecular
      mechanism underlying activity-dependent regulation of fine-scale topography is
      poorly understood. Molecular analysis of the spatial relationship between
      adjacent afferent terminals requires reliable localization of the presynaptic
      terminals of single neurons as well as genetic manipulations with single-cell
      resolution in vivo. Although both requirements can potentially be met in
      Drosophila melanogaster [5, 6], no activity-dependent topographic system has been
      identified in flies [7]. Here we report a topographic system that is shaped by
      neuronal activity in Drosophila. With this system, we found that topographic
      separation of the presynaptic terminals of adjacent nociceptive neurons requires
      different levels of Trim9, an evolutionarily conserved signaling molecule [8-11].
      Neural activity regulates Trim9 protein levels to direct fine-scale topography of
      sensory afferents. This study offers both a novel mechanism by which neural
      activity directs fine-scale topography of axon terminals and a new system to
      study this process at single-neuron resolution.

PMID- 24746794
TI  - Vulnerability of coral reef fisheries to a loss of structural complexity.
AB  - Coral reefs face a diverse array of threats, from eutrophication and overfishing
      to climate change. As live corals are lost and their skeletons eroded, the
      structural complexity of reefs declines. This may have important consequences for
      the survival and growth of reef fish because complex habitats mediate predator
      prey interactions [1, 2] and influence competition [3-5] through the provision of
      prey refugia. A positive correlation exists between structural complexity and
      reef fish abundance and diversity in both temperate and tropical ecosystems [6
      10]. However, it is not clear how the diversity of available refugia interacts
      with individual predator-prey relationships to explain emergent properties at the
      community scale. Furthermore, we do not yet have the ability to predict how
      habitat loss might affect the productivity of whole reef communities and the
      fisheries they support. Using data from an unfished reserve in The Bahamas, we
      find that structural complexity is associated not only with increased fish
      biomass and abundance, but also with nonlinearities in the size spectra of fish,
      implying disproportionately high abundances of certain size classes. By
      developing a size spectrum food web model that links the vulnerability of prey to
      predation with the structural complexity of a reef, we show that these
      nonlinearities can be explained by size-structured prey refugia that reduce
      mortality rates and alter growth rates in different parts of the size spectrum.
      Fitting the model with data from a structurally complex habitat, we predict that
      a loss of complexity could cause more than a 3-fold reduction in fishery
      productivity.

PMID- 24746795
TI  - Regulation of clathrin-mediated endocytosis by dynamic ubiquitination and
      deubiquitination.
AB  - BACKGROUND: Clathrin-mediated endocytosis in budding yeast requires the regulated
      recruitment and disassociation of more than 60 proteins at discrete plasma
      membrane punctae. Posttranslational modifications such as ubiquitination may play
      important regulatory roles in this highly processive and ordered process.
      However, although ubiquitination plays an important role in cargo selection,
      functions for ubiquitination of the endocytic machinery are not known. RESULTS:
      We identified the deubiquitinase (DUB) Ubp7 as a late-arriving endocytic protein.
      Deletion of the DUBs Ubp2 and Ubp7 resulted in elongation of endocytic coat
      protein lifetimes at the plasma membrane and recruitment of endocytic proteins to
      internal membranes. These phenotypes could be replicated by expressing a
      permanently ubiquitinated version of Ede1, the yeast Eps15 homolog, which is
      implicated in endocytic site initiation, whereas EDE1 deletion partially
      suppressed the DUB deletion phenotype. Both DUBs are capable of deubiquitinating
      Ede1 in vitro. CONCLUSIONS: Deubiquitination regulates formation of endocytic
      sites and stability of the endocytic coat. This regulation appears to occur
      through Ede1, because permanently ubiquitinated Ede1 phenocopies deletion of UBP2
      and UBP7. Moreover, incomplete suppression of the ubp2Delta ubp7Delta phenotype
      by ede1Delta indicates that ubiquitination and deubiquitination are likely to
      regulate additional components of the endocytic machinery.

PMID- 24746796
TI  - Pattern completion in multielement event engrams.
AB  - Personally experienced events include multiple elements, such as locations,
      people, and objects. These events are thought to be stored in episodic memory as
      coherent representations [1] that allow the retrieval of all elements from a
      partial cue ("pattern completion" [2-6]). However, direct evidence for coherent
      multielement representations is lacking. Their presence would predict that
      retrieval of one element from an event should be dependent on retrieval of the
      other elements from that event. If we remember where we were, we should be more
      likely to remember who we met and what object they gave us. Here we provide
      evidence for this type of dependency in remembering three-element events.
      Dependency was seen when all three elements were encoded simultaneously, or when
      the three overlapping pairwise associations comprising an event were learned on
      separate trials. However, dependency was only seen in the separated encoding
      condition when all possible within-event associations were encoded. These results
      suggest that episodic memories are stored as coherent representations in which
      associations between all within-event elements allow retrieval via pattern
      completion. They also show that related experiences encountered at different
      times can be flexibly integrated into these coherent representations.

PMID- 24746797
TI  - Female penis, male vagina, and their correlated evolution in a cave insect.
AB  - Sex-specific elaborations are common in animals and have attracted the attention
      of many biologists, including Darwin [1]. It is accepted that sexual selection
      promotes the evolution of sex-specific elaborations. Due to the faster
      replenishment rate of gametes, males generally have higher potential reproductive
      and optimal mating rates than females. Therefore, sexual selection acts strongly
      on males [2], leading to the rapid evolution and diversification of male
      genitalia [3]. Male genitalia are sometimes used as devices for coercive holding
      of females as a result of sexual conflict over mating [4, 5]. In contrast, female
      genitalia are usually simple. Here we report the reversal of intromittent organs
      in the insect genus Neotrogla (Psocodea: Prionoglarididae) from Brazilian caves.
      Females have a highly elaborate, penis-like structure, the gynosome, while males
      lack an intromittent organ. The gynosome has species-specific elaborations, such
      as numerous spines that fit species-specific pouches in the simple male genital
      chamber. During prolonged copulation (~40-70 hr), a large and potentially
      nutritious ejaculate is transferred from the male via the gynosome. The
      correlated genital evolution in Neotrogla is probably driven by reversed sexual
      selection with females competing for seminal gifts. Nothing similar is known
      among sex-role reversed animals.

PMID- 24746798
TI  - Germ-granule components prevent somatic development in the C. elegans germline.
AB  - Specialized ribonucleoprotein organelles collectively known as germ granules are
      found in the germline cytoplasm from worms to humans [1]. In Drosophila, germ
      granules have been implicated in germline determination [2]. C. elegans germ
      granules, known as P granules, do not appear to be required for primordial germ
      cell (PGC) determination [3], but their components are still needed for fertility
      [4-6]. One potential role for P granules is to maintain germline fate and
      totipotency. This is suggested by the loss of P granules from germ cells that
      transform into somatic cell types, e.g., in germlines lacking MEX-3 and GLD-1 or
      upon neuronal induction by CHE-1 [7, 8]. However, it has not been established
      whether loss of P granules is the cause or effect of cell fate transformation. To
      test cause and effect, we severely compromised P granules by simultaneously
      knocking down factors that nucleate granule formation (PGL-1 and PGL-3) and
      promote their perinuclear localization (GLH-1 and GLH-4) [9] and investigated
      whether this causes germ cells to lose totipotency and initiate somatic
      reprogramming. We found that compromising P granules causes germ cells to express
      neuronal and muscle markers and send out neurite-like projections, suggesting
      that P granules maintain totipotency and germline identity by antagonizing
      somatic fate.

PMID- 24746799
TI  - Thalamic control of human attention driven by memory and learning.
AB  - The role of the thalamus in high-level cognition-attention, working memory (WM),
      rule-based learning, and decision making-remains poorly understood, especially in
      comparison to that of cortical frontoparietal networks [1-3]. Studies of visual
      thalamus have revealed important roles for pulvinar and lateral geniculate
      nucleus in visuospatial perception and attention [4-10] and for mediodorsal
      thalamus in oculomotor control [11]. Ventrolateral thalamus contains subdivisions
      devoted to action control as part of a circuit involving the basal ganglia [12,
      13] and motor, premotor, and prefrontal cortices [14], whereas anterior thalamus
      forms a memory network in connection with the hippocampus [15]. This connectivity
      profile suggests that ventrolateral and anterior thalamus may represent a nexus
      between mnemonic and control functions, such as action or attentional selection.
      Here, we characterize the role of thalamus in the interplay between memory and
      visual attention. We show that ventrolateral lesions impair the influence of WM
      representations on attentional deployment. A subsequent fMRI study in healthy
      volunteers demonstrates involvement of ventrolateral and, notably, anterior
      thalamus in biasing attention through WM contents. To further characterize the
      memory types used by the thalamus to bias attention, we performed a second fMRI
      study that involved learning of stimulus-stimulus associations and their
      retrieval from long-term memory to optimize attention in search. Responses in
      ventrolateral and anterior thalamic nuclei tracked learning of the predictiveness
      of these abstract associations and their use in directing attention. These
      findings demonstrate a key role for human thalamus in higher-level cognition,
      notably, in mnemonic biasing of attention. 

PMID- 24746800
TI  - Transforming growth factor beta (TGFbeta) plays a crucial role in prolonging
      allograft survival in an allodepletion ("pruning") skin transplant model.
AB  - Adoptive cell therapies involving cell manipulation to achieve tolerance are
      increasingly being studied in animal models and in human trials. We have
      demonstrated that the specific removal of allo-stimulated dividing cells (or
      "pruning") promotes long-term allograft survival across a major MHC mismatch in
      transplant models including skin, heart and islet transplants. In this study, we
      examine the role of transforming growth factor beta (TGFbeta), an important
      regulatory cytokine, on allograft survival in our allodepletion or "pruning" skin
      transplant model. Increased proliferation of CD4(+) T cells was observed
      following allo-stimulation of BALB/c spleen cells (labeled with CFSE) in the
      presence of the regulatory cytokines TGFbeta and (interleukin-2) IL-2 in a mixed
      lymphocyte culture (MLC). Expression of the regulatory gene forkhead box-3
      (FoxP3) was increased in both the allo-stimulated non-dividing (ND) (CFSE(high))
      and dividing (D) (CFSE(low)) CD4(+) T cell populations, with the highest
      expression found in the D CD4(+) T cell population. Mice reconstituted with allo
      stimulated ND CD4(+) T cells following TGFbeta/IL-2 stimulation showed prolonged
      allograft survival, similar to previous data. Significantly, TGFbeta/IL-2
      stimulation prevented acute rejection of allografts across a major MHC mismatch
      in the presence of highly activated allo-stimulated D CD4(+) T cells. Blockade of
      TGFbeta promoted rejection of allografts even following depletion of allo
      stimulated D CD4(+) T cells. These studies support a crucial role for TGFbeta in
      the survival of allografts and shows that regulatory cytokines TGFbeta/IL2 can
      delay the rejection of allografts, even in the presence of highly activated
      alloreactive T cells. 

PMID- 24746801
TI  - Glucocorticoid resistance in dialysis patients reduces long-term graft survival
      after kidney transplantation.
AB  - Glucocorticoid (GC) resistance has been observed in chronic kidney disease (CKD)
      patients on dialysis. It can be evaluated by binding assays based on the
      dissociation constant (Kd), which is inversely proportional to ligand affinity.
      CKD patients with GC resistance had increased number of acute rejection episodes.
      We followed up 26 patients that underwent kidney transplantation to observe
      whether GC resistance could affect the response to acute rejection episode pulse
      therapy and the long-term allograft outcome. Using Kaplan-Meier survival curve,
      GC resistant patients showed lower acute rejection-free survival (p=0.03) and
      lower kidney allograft survival (p=0.008). No difference was found regarding
      number of deaths. Multivariate logistic regression showed that high Kd value was
      an independent predictor of lower kidney allograft survival (p=0.001). There was
      a negative Spearman correlation between Kd and kidney allograft survival (r=
      0.88, p=0.03). In conclusion, our findings indicate the usefulness of binding
      assay performed previously to kidney transplantation to define GC resistance. In
      addition, the dissociation constant (Kd) is a reliable and independent predictive
      marker of higher frequency of acute rejection episodes, lower rejection-free
      graft survival, poor response of acute rejection episodes to methylprednisolone
      pulse therapy, and lower kidney allograft survival in a long-term follow-up. 

PMID- 24746802
TI  - Maternally inherited diabetes and deafness (MIDD): diagnosis and management.
AB  - Maternally inherited diabetes with deafness is rare diabetes caused by a
      mitochondrial DNA defect. 85% of cases are associated with m.3243A>G mutation. It
      is important to diagnose this form of diabetes because of the unique management
      issues and associated comorbidities. A very strong family history of diabetes,
      deafness and presence of retinal dystrophy should prompt an investigation for
      MIDD. Microvascular complications out of keeping with duration of diabetes are
      another clue to the diagnosis. Retinal and renal manifestations of mitochondrial
      disease may be confused for diabetic complications. Glutamic acid decarboxylase
      (GAD) autoantibody negativity in a nonobese diabetic is another clue. Cardiac
      conduction defects and GDM may also raise suspicion as to the diagnosis.
      Recognizing this etiology of DM should promote family screening, genetic
      counseling, screening of associated comorbidities, avoidance of metformin, and
      cautious use of statins. We report a 77 years old lady with MIDD who was being
      followed up as insulin requiring type 2 diabetes. We then identified 5 more
      patients with MIDD in the same clinic. They all had A3243 mutation with
      characteristic clinical presentation. The pharmacological approaches discussed in
      the paper are unlikely to work in these patients as they were diagnosed late.

PMID- 24746803
TI  - The diet of Templar Knights: their secret to longevity?

PMID- 24746804
TI  - Methionine metabolism regulates maintenance and differentiation of human
      pluripotent stem cells.
AB  - Mouse embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) are
      in a high-flux metabolic state, with a high dependence on threonine catabolism.
      However, little is known regarding amino acid metabolism in human ESCs/iPSCs. We
      show that human ESCs/iPSCs require high amounts of methionine (Met) and express
      high levels of enzymes involved in Met metabolism. Met deprivation results in a
      rapid decrease in intracellular S-adenosylmethionine (SAM), triggering the
      activation of p53-p38 signaling, reducing NANOG expression, and poising human
      iPSC/ESCs for differentiation, follow by potentiated differentiation into all
      three germ layers. However, when exposed to prolonged Met deprivation, the cells
      undergo apoptosis. We also show that human ESCs/iPSCs have regulatory systems to
      maintain constant intracellular Met and SAM levels. Our findings show that SAM is
      a key regulator for maintaining undifferentiated pluripotent stem cells and
      regulating their differentiation. 

PMID- 24746805
TI  - Grb10 promotes lipolysis and thermogenesis by phosphorylation-dependent feedback
      inhibition of mTORC1.
AB  - Identification of key regulators of lipid metabolism and thermogenic functions
      has important therapeutic implications for the current obesity and diabetes
      epidemic. Here, we show that Grb10, a direct substrate of mechanistic/mammalian
      target of rapamycin (mTOR), is expressed highly in brown adipose tissue, and its
      expression in white adipose tissue is markedly induced by cold exposure. In
      adipocytes, mTOR-mediated phosphorylation at Ser501/503 switches the binding
      preference of Grb10 from the insulin receptor to raptor, leading to the
      dissociation of raptor from mTOR and downregulation of mTOR complex 1 (mTORC1)
      signaling. Fat-specific disruption of Grb10 increased mTORC1 signaling in adipose
      tissues, suppressed lipolysis, and reduced thermogenic function. The effects of
      Grb10 deficiency on lipolysis and thermogenesis were diminished by rapamycin
      administration in vivo. Our study has uncovered a unique feedback mechanism
      regulating mTORC1 signaling in adipose tissues and identified Grb10 as a key
      regulator of adiposity, thermogenesis, and energy expenditure.

PMID- 24746806
TI  - Pancreatic beta cell dedifferentiation in diabetes and redifferentiation
      following insulin therapy.
AB  - Diabetes is characterized by "glucotoxic" loss of pancreatic beta cell function
      and insulin content, but underlying mechanisms remain unclear. A mouse model of
      insulin-secretory deficiency induced by beta cell inexcitability (K(ATP) gain of
      function) demonstrates development of diabetes and reiterates the features of
      human neonatal diabetes. In the diabetic state, beta cells lose their mature
      identity and dedifferentiate to neurogenin3-positive and insulin-negative cells.
      Lineage-tracing experiments show that dedifferentiated cells can subsequently
      redifferentiate to mature neurogenin3-negative, insulin-positive beta cells after
      lowering of blood glucose by insulin therapy. We demonstrate here that beta cell
      dedifferentiation, rather than apoptosis, is the main mechanism of loss of
      insulin-positive cells, and redifferentiation accounts for restoration of insulin
      content and antidiabetic drug responsivity in these animals. These results may
      help explain gradual decrease in beta cell mass in long-standing diabetes and
      recovery of beta cell function and drug responsivity in type 2 diabetic patients
      following insulin therapy, and they suggest an approach to rescuing "exhausted"
      beta cells in diabetes.

PMID- 24746807
TI  - Pigmented oral carcinoma in situ: a case report and literature review.
AB  - Oral melanotic lesions, including melanin pigmentation, melanocytic nevus, and
      malignant melanoma, are well-recognized pathologic entities. However, melanocytic
      proliferation within malignant oral mucosal lesions is not well documented. We
      report the unusual case of a 53-year-old Japanese man who developed oral
      carcinoma in situ (CIS) with melanocytic proliferation and melanin pigmentation
      in the epithelial layer. The patient, a nonsmoker and an opportunistic drinker,
      presented with a brown tongue lesion. Initial examination found a large brown
      pigmented area and multiple small white patchy areas on the right tongue border.
      The pigmentation had an ill-defined border with uneven color distribution.
      Physical examination found no abnormalities. Ultrasonography did not find a
      deeply infiltrating lesion. Oral mucosal malignant melanoma in situ was
      diagnosed, and partial tongue resection was performed. Histopathologic
      examination found oral pigmented CIS. To the best of our knowledge, this is only
      the third reported case of oral pigmented CIS. 

PMID- 24746808
TI  - Image gently: enhancing radiation protection during pediatric imaging.

PMID- 24746809
TI  - Mothers' perceptions about the nutritional status of their overweight children: a
      systematic review.
AB  - OBJECTIVE: this systematic review aims to explore and describe the studies that
      have as a primary outcome the identification of mothers' perception of the
      nutritional status of their children. SOURCES: the PubMed, Embase, LILACS, and
      SciELO databases were researched, regardless of language or publication date. The
      terms used for the search, with its variants, were: Nutritional Status,
      Perception, Mother, Maternal, Parents, Parental. SUMMARY OF THE FINDINGS: after
      screening of 167 articles, 41 were selected for full text reading, of which 17
      were included in the review and involved the evaluation of the perception of
      mothers on the nutritional status of 57,700 children and adolescents. The
      methodological quality of the studies ranged from low to excellent. The
      proportion of mothers who inadequately perceived the nutritional status of their
      children was high, and was the most common underestimation for children with
      overweight or obesity. CONCLUSION: despite the increasing prevalence of obesity
      in pediatric age, mothers have difficulty in properly perceiving the nutritional
      status of their children, which may compromise referral to treatment programs.

PMID- 24746810
TI  - Author's reply: Z-Score: Fenton 2013. Ten-year update.

PMID- 24746811
TI  - Elongated styloid process as a cause of facial pain.

PMID- 24746812
TI  - Repair of radiographic hip joint in juvenile rheumatoid arthritis patients
      treated with etanercept plus methotrexate.
AB  - For patients suffering from rheumatoid arthritis (RA), structural damage, i.e.
      bone erosion and joint space narrowing, is a major factor leading to functional
      disability. Negative radiographic progression has been shown in joints,
      especially in RA patients treated with tumor necrosis factor alpha (TNFalpha)
      inhibitors in combination with methotrexate. Bone erosion repair in small joints
      have been observed but only one study selected large weight-bearing joints. We
      reported 2 cases of patients with severe seropositive juvenile RA who shown
      improvement of joint space narrowing and subchondral erosion in hip joint when
      treated with etanercept in combination with methotrexate for at least 1year. Two
      Japanese cases were also published but with different TNF inhibitors. The
      mechanisms of bone erosion or joint space narrowing repair are unclear. One study
      investigated whether bone erosions in rheumatoid arthritis patients show evidence
      of repair in metacarpophalangeal joints when treated with TNF inhibitors and MTX.
      These results suggested that repair in RA emerged from the bone marrow and the
      endosteal lining rather than the periosteal compartment. No study investigated
      joint space narrowing repair in hip joint in rheumatoid arthritis patients.
      Larger studies needed to confirm joint space narrowing improvement in hip joint
      in patients treated with TNF inhibitors and to explain the mechanisms of repair.

PMID- 24746813
TI  - proBDNF negatively regulates neuronal remodeling, synaptic transmission, and
      synaptic plasticity in hippocampus.
AB  - Experience-dependent plasticity shapes postnatal development of neural circuits,
      but the mechanisms that refine dendritic arbors, remodel spines, and impair
      synaptic activity are poorly understood. Mature brain-derived neurotrophic factor
      (BDNF) modulates neuronal morphology and synaptic plasticity, including long-term
      potentiation (LTP) via TrkB activation. BDNF is initially translated as proBDNF,
      which binds p75(NTR). In vitro, recombinant proBDNF modulates neuronal structure
      and alters hippocampal long-term plasticity, but the actions of endogenously
      expressed proBDNF are unclear. Therefore, we generated a cleavage-resistant
      probdnf knockin mouse. Our results demonstrate that proBDNF negatively regulates
      hippocampal dendritic complexity and spine density through p75(NTR). Hippocampal
      slices from probdnf mice exhibit depressed synaptic transmission, impaired LTP,
      and enhanced long-term depression (LTD) in area CA1. These results suggest that
      proBDNF acts in vivo as a biologically active factor that regulates hippocampal
      structure, synaptic transmission, and plasticity, effects that are distinct from
      those of mature BDNF. 

PMID- 24746814
TI  - Morning and evening oscillators cooperate to reset circadian behavior in response
      to light input.
AB  - Light is a crucial input for circadian clocks. In Drosophila, short light
      exposure can robustly shift the phase of circadian behavior. The model for this
      resetting posits that circadian photoreception is cell autonomous: CRYPTOCHROME
      senses light, binds to TIMELESS (TIM), and promotes its degradation, which is
      mediated by JETLAG (JET). However, it was recently proposed that interactions
      between circadian neurons are also required for phase resetting. We identify two
      groups of neurons critical for circadian photoreception: the morning (M) and the
      evening (E) oscillators. These neurons work synergistically to reset rhythmic
      behavior. JET promotes acute TIM degradation cell autonomously in M and E
      oscillators but also nonautonomously in E oscillators when expressed in M
      oscillators. Thus, upon light exposure, the M oscillators communicate with the E
      oscillators. Because the M oscillators drive circadian behavior, they must also
      receive inputs from the E oscillators. Hence, although photic TIM degradation is
      largely cell autonomous, neural cooperation between M and E oscillators is
      critical for circadian behavioral photoresponses. 

PMID- 24746815
TI  - Cholesterol regulates Syntaxin 6 trafficking at trans-Golgi network endosomal
      boundaries.
AB  - Inhibition of cholesterol export from late endosomes causes cellular cholesterol
      imbalance, including cholesterol depletion in the trans-Golgi network (TGN).
      Here, using Chinese hamster ovary (CHO) Niemann-Pick type C1 (NPC1) mutant cell
      lines and human NPC1 mutant fibroblasts, we show that altered cholesterol levels
      at the TGN/endosome boundaries trigger Syntaxin 6 (Stx6) accumulation into VAMP3,
      transferrin, and Rab11-positive recycling endosomes (REs). This increases
      Stx6/VAMP3 interaction and interferes with the recycling of alphaVbeta3 and
      alpha5beta1 integrins and cell migration, possibly in a Stx6-dependent manner. In
      NPC1 mutant cells, restoration of cholesterol levels in the TGN, but not
      inhibition of VAMP3, restores the steady-state localization of Stx6 in the TGN.
      Furthermore, elevation of RE cholesterol is associated with increased amounts of
      Stx6 in RE. Hence, the fine-tuning of cholesterol levels at the TGN-RE boundaries
      together with a subset of cholesterol-sensitive SNARE proteins may play a
      regulatory role in cell migration and invasion. 

PMID- 24746816
TI  - Impaired p32 regulation caused by the lymphoma-prone RECQ4 mutation drives
      mitochondrial dysfunction.
AB  - Mitochondrial DNA (mtDNA) encodes proteins that are important for ATP biogenesis.
      Therefore, changes in mtDNA copy number will have profound consequences on cell
      survival and proliferation. RECQ4 DNA helicase participates in both nuclear DNA
      and mtDNA synthesis. However, the mechanism that balances the distribution of
      RECQ4 in the nucleus and mitochondria is unknown. Here, we show that RECQ4 forms
      protein complexes with Protein Phosphatase 2A (PP2A), nucleophosmin (NPM), and
      mitochondrial p32 in different cellular compartments. Critically, the interaction
      with p32 negatively controls the transport of both RECQ4 and its chromatin
      associated replication factor, MCM10, from the nucleus to mitochondria. Amino
      acids that are deleted in the most common cancer-associated RECQ4 mutation are
      required for the interaction with p32. Hence, this RECQ4 mutant, which is no
      longer regulated by p32 and is enriched in the mitochondria, interacts with the
      mitochondrial replication helicase PEO1 and induces abnormally high levels of
      mtDNA synthesis. 

PMID- 24746817
TI  - Necrosis-driven systemic immune response alters SAM metabolism through the FOXO
      GNMT axis.
AB  - Sterile inflammation triggered by endogenous factors is thought to contribute to
      the pathogenesis of acute and chronic inflammatory diseases. Here, we demonstrate
      that apoptosis-deficient mutants spontaneously develop a necrosis-driven systemic
      immune response in Drosophila and provide an in vivo model for studying the
      organismal response to sterile inflammation. Metabolomic analysis of hemolymph
      from apoptosis-deficient mutants revealed increased sarcosine and reduced S
      adenosyl-methionine (SAM) levels due to glycine N-methyltransferase (Gnmt)
      upregulation. We showed that Gnmt was elevated in response to Toll activation
      induced by the local necrosis of wing epidermal cells. Necrosis-driven
      inflammatory conditions induced dFoxO hyperactivation, leading to an energy
      wasting phenotype. Gnmt was cell-autonomously upregulated by dFoxO in the fat
      body as a possible rheostat for controlling energy loss, which functioned during
      fasting as well as inflammatory conditions. We propose that the dFoxO-Gnmt axis
      is essential for the maintenance of organismal SAM metabolism and energy
      homeostasis. 

PMID- 24746818
TI  - Isolation and molecular characterization of circulating melanoma cells.
AB  - Melanoma is an invasive malignancy with a high frequency of blood-borne
      metastases, but circulating tumor cells (CTCs) have not been readily isolated. We
      adapted microfluidic CTC capture to a tamoxifen-driven B-RAF/PTEN mouse melanoma
      model. CTCs were detected in all tumor-bearing mice and rapidly declined after B
      RAF inhibitor treatment. CTCs were shed early from localized tumors, and a short
      course of B-RAF inhibition following surgical resection was sufficient to
      dramatically suppress distant metastases. The large number of CTCs in melanoma
      bearing mice enabled a comparison of RNA-sequencing profiles with matched primary
      tumors. A mouse melanoma CTC-derived signature correlated with invasiveness and
      cellular motility in human melanoma. CTCs were detected in smaller numbers in
      patients with metastatic melanoma and declined with successful B-RAF-targeted
      therapy. Together, the capture and molecular characterization of CTCs provide
      insight into the hematogenous spread of melanoma. 

PMID- 24746819
TI  - Conversion of quiescent niche cells to somatic stem cells causes ectopic niche
      formation in the Drosophila testis.
AB  - Adult stem cells reside in specialized regulatory microenvironments, or niches,
      where local signals ensure stem cell maintenance. The Drosophila testis contains
      a well-characterized niche wherein signals from postmitotic hub cells promote
      maintenance of adjacent germline stem cells and somatic cyst stem cells (CySCs).
      Hub cells were considered to be terminally differentiated; here, we show that
      they can give rise to CySCs. Genetic ablation of CySCs triggers hub cells to
      transiently exit quiescence, delaminate from the hub, and convert into functional
      CySCs. Ectopic Cyclin D-Cdk4 expression in hub cells is also sufficient to
      trigger their conversion into CySCs. In both cases, this conversion causes the
      formation of multiple ectopic niches over time. Therefore, our work provides a
      model for understanding how oncogenic mutations in quiescent niche cells could
      promote loss of quiescence, changes in cell fate, and aberrant niche expansion. 

PMID- 24746820
TI  - Functional genomic analysis of human mitochondrial RNA processing.
AB  - Both strands of human mtDNA are transcribed in continuous, multigenic units that
      are cleaved into the mature rRNAs, tRNAs, and mRNAs required for respiratory
      chain biogenesis. We sought to systematically identify nuclear-encoded proteins
      that contribute to processing of mtRNAs within the organelle. First, we devised
      and validated a multiplex MitoString assay that quantitates 27 mature and
      precursor mtDNA transcripts. Second, we applied MitoString profiling to evaluate
      the impact of silencing each of 107 mitochondrial-localized, predicted RNA
      binding proteins. With the resulting data set, we rediscovered the roles of
      recently identified RNA-processing enzymes, detected unanticipated roles of known
      disease genes in RNA processing, and identified new regulatory factors. We
      demonstrate that one such factor, FASTKD4, modulates the half-lives of a subset
      of mt-mRNAs and associates with mtRNAs in vivo. MitoString profiling may be
      useful for diagnosing and deciphering the pathogenesis of mtDNA disorders. 

PMID- 24746821
TI  - Uterine leiomyoma-linked MED12 mutations disrupt mediator-associated CDK
      activity.
AB  - Somatic mutations in exon 2 of the RNA polymerase II transcriptional Mediator
      subunit MED12 occur at very high frequency (~70%) in uterine leiomyomas. However,
      the influence of these mutations on Mediator function and the molecular basis for
      their tumorigenic potential remain unknown. To clarify the impact of these
      mutations, we used affinity-purification mass spectrometry to establish the
      global protein-protein interaction profiles for both wild-type and mutant MED12.
      We found that uterine leiomyoma-linked mutations in MED12 led to a highly
      specific decrease in its association with Cyclin C-CDK8/CDK19 and loss of
      Mediator-associated CDK activity. Mechanistically, this occurs through disruption
      of a MED12-Cyclin C binding interface that we also show is required for MED12
      mediated stimulation of Cyclin C-dependent CDK8 kinase activity. These findings
      indicate that uterine leiomyoma-linked mutations in MED12 uncouple Cyclin C
      CDK8/19 from core Mediator and further identify the MED12/Cyclin C interface as a
      prospective therapeutic target in CDK8-driven cancers. 

PMID- 24746822
TI  - Hepatic rRNA transcription regulates high-fat-diet-induced obesity.
AB  - Ribosome biosynthesis is a major intracellular energy-consuming process. We
      previously identified a nucleolar factor, nucleomethylin (NML), which regulates
      intracellular energy consumption by limiting rRNA transcription. Here, we show
      that, in livers of obese mice, the recruitment of NML to rRNA gene loci is
      increased to repress rRNA transcription. To clarify the relationship between
      obesity and rRNA transcription, we generated NML-null (NML-KO) mice. NML-KO mice
      show elevated rRNA level, reduced ATP concentration, and reduced lipid
      accumulation in the liver. Furthermore, in high-fat-diet (HFD)-fed NML-KO mice,
      hepatic rRNA levels are not decreased. Both weight gain and fat accumulation in
      HFD-fed NML-KO mice are significantly lower than those in HFD-fed wild-type mice.
      These findings indicate that rRNA transcriptional activation promotes hepatic
      energy consumption, which alters hepatic lipid metabolism. Namely, hepatic rRNA
      transcriptional repression by HFD feeding is essential for energy storage. 

PMID- 24746823
TI  - Persistent replicative stress alters polycomb phenotypes and tissue homeostasis
      in Drosophila melanogaster.
AB  - Polycomb group (PcG) proteins establish and maintain genetic programs that
      regulate cell-fate decisions. Drosophila multi sex combs (mxc) was categorized as
      a PcG gene based on a classical Polycomb phenotype and genetic interactions;
      however, a mechanistic connection between Polycomb and Mxc has not been
      elucidated. Hypomorphic alleles of mxc are characterized by male and female
      sterility and ectopic sex combs. Mxc is an important regulator of histone
      synthesis, and we find that increased levels of the core histone H3 in mxc
      mutants result in replicative stress and a persistent DNA damage response (DDR).
      Germline loss, ectopic sex combs and the DDR are suppressed by reducing H3 in mxc
      mutants. Conversely, mxc phenotypes are enhanced when the DDR is abrogated.
      Importantly, replicative stress induced by hydroxyurea treatment recapitulated
      mxc germline phenotypes. These data reveal how persistent replicative stress
      affects gene expression, tissue homeostasis, and maintenance of cellular identity
      in vivo. 

PMID- 24746825
TI  - Antimicrobial resistance surveillance in Europe: regional pooling of national
      data from a small number of sites can be misleading.

PMID- 24746824
TI  - Impeded Nedd4-1-mediated Ras degradation underlies Ras-driven tumorigenesis.
AB  - RAS genes are among the most frequently mutated proto-oncogenes in cancer.
      However, how Ras stability is regulated remains largely unknown. Here, we report
      a regulatory loop involving the E3 ligase Nedd4-1, Ras, and PTEN. We found that
      Ras signaling stimulates the expression of Nedd4-1, which in turn acts as an E3
      ubiquitin ligase that regulates Ras levels. Importantly, Ras activation, either
      by oncogenic mutations or by epidermal growth factor (EGF) signaling, prevents
      Nedd4-1-mediated Ras ubiquitination. This leads to Ras-induced Nedd4-1
      overexpression, and subsequent degradation of the tumor suppressor PTEN in both
      human cancer samples and cancer cells. Our study thus unravels the molecular
      mechanisms underlying the interplay of Ras, Nedd4-1, and PTEN and suggests a
      basis for the high prevalence of Ras-activating mutations and EGF hypersignaling
      in cancer. 

PMID- 24746826
TI  - Molecular characterization of Klebsiella pneumoniae isolated from renal
      transplanted patients: virulence markers, extended-spectrum beta-lactamases, and
      genetic relatedness.
AB  - The objective was to characterize virulence markers and beta-lactam resistance in
      Klebsiella pneumoniae isolates from renal transplant patients and to evaluate
      their genetic relatedness. Two main genetic lineages were detected: 1 carried
      bla(CTX-M-15) not associated to IncFIIA plasmid replicon, which was found on the
      other lineage not expressing CTX-M-type enzyme. PAI III(536) and PAI II(CFT073)
      were detected for the first time in K. pneumoniae in 1 clone, while the
      siderophore kfu was carried by the other, with only PAI IV(536). The molecular
      data indicate colonization before admission and fuel the discussion on
      implementation of antibiotherapy before surgery.

PMID- 24746827
TI  - Melphalan, alone or conjugated to an FSH-beta peptide, kills murine testicular
      cells in vitro and transiently suppresses murine spermatogenesis in vivo.
AB  - New approaches to sterilizing male animals are needed to control captive and wild
      animal populations. We sought to develop a nonsurgical method of permanent
      sterilization for male animals by administering the gonadotoxicant melphalan
      conjugated to peptides derived from the beta-chain of FSHbeta. We hypothesized
      that conjugating melphalan to FSHbeta peptides would magnify the gonadotoxic
      effects of melphalan while minimizing systemic toxicity. The ability of
      conjugates of melphalan and FSHbeta peptides to kill murine testicular cells was
      first tested in vitro in a three-dimensional testicular cell coculture system. In
      this system, melphalan caused considerable cell death as measured both by
      increases in lactate dehydrogenase concentrations in the culture supernatant and
      direct visualization of the cultures. Of the conjugates tested, melphalan
      conjugated to a 20-amino acid peptide derived from human FSHbeta consisting of
      amino acids 33 to 53 (FSHbeta (33-53)-melphalan) was very potent, with cell
      cytotoxicity and lactate dehydrogenase release roughly one-half that of
      melphalan. The effects of melphalan and FSHbeta (33-53)-melphalan on
      spermatogenesis were then tested in vivo in mature C56Bl/6 male mice. Four weeks
      after intraperitoneal injection, all mice treated with either FSHbeta (33-53)
      melphalan or melphalan had approximately 75% reductions in testicular spermatid
      counts compared with control animals. Testicular histology revealed significant
      reduction in mature spermatids and spermatocytes in most tubules. However, 12
      weeks after the injection, testicular spermatid counts and histology were similar
      to controls, except in one animal receiving FSHbeta (33-53)-melphalan that had no
      apparent spermatogenesis. We conclude that melphalan and FSHbeta (33-53)
      melphalan are potent gonadotoxicants in male mice resulting in marked suppression
      of spermatogenesis 4 weeks after a single intraperitoneal injection. However,
      this effect is transient in most mice as spermatogenesis is similar to control
      animals 12 weeks after drug administration. Melphalan or FSHbeta (33-53)
      melphalan may be useful for the temporary control of fertility in male animals,
      but additional research will be needed to develop a single dose method of
      permanent sterilization for male animals. 

PMID- 24746829
TI  - Increasing long-chain n-3PUFA consumption improves small peripheral artery
      function in patients at intermediate-high cardiovascular risk.
AB  - Dietary long-chain n-3 polyunsaturated fatty acids (LCn-3PUFA) improve
      endothelial function in medium-large-sized arteries, but effects on small
      peripheral arteries, responsible for most arterial resistance, are little known.
      We investigated the effects of increasing LCn-3PUFA intake with the usual diet on
      small artery reactive hyperemia index (saRHI). Within a clinical trial evaluating
      the effects of 1 year of intensive lifestyle intervention versus standard care on
      cardiovascular markers in subjects at risk, we selected 108 participants
      regardless of treatment allocation (n=47 standard care; n=61 intensive
      intervention) with complete baseline and follow-up information on dietary,
      clinical, saRHI and biochemical data, including biomarkers of inflammation and
      endothelial activation. At the end of follow-up, saRHI increased across tertiles
      of change in dietary LCn-3PUFA. Subjects in the top tertile (increased LCn-3PUFA
      intake) increased serum ApoA1 and decreased hs-CRP, serum TNF-alpha, sICAM-1,
      sVCAM-1 and oxLDL from baseline. After pooling data, in unadjusted models,
      changes in saRHI significantly correlated to changes in LCn-3PUFA intake and
      ApoA1 (directly) and changes in systolic blood pressure, waist circumference, TNF
      alpha, sVCAM-1 and sE-selectin (inversely). In a multivariate model, changes in
      dietary LCn-3PUFA were significantly associated with changes in saRHI [B=0.08
      (95% confidence interval=0.083-0.291) for an increase by 100 mg/day]. Systolic
      blood pressure was inversely associated with saRHI changes [B=-0.203 (-0.441 to 
      0.029) for a 9-mmHg increase]. We conclude that increased dietary consumption of
      LCn-3PUFA might be a cost-effective strategy to improve peripheral vasoactivity. 

PMID- 24746828
TI  - beta-Carotene inhibits neuroblastoma cell invasion and metastasis in vitro and in
      vivo by decreasing level of hypoxia-inducible factor-1alpha.
AB  - Neuroblastoma is the most prevalent extracranial solid tumor in childhood and has
      poor clinical outcome due to its high potential for metastasis. Consequently, an
      understanding of the mechanisms that modulate cancer cell invasion, migration and
      metastasis is important for the development of more effective chemotherapeutic
      agents. While beta-carotene is a vitamin A precursor that has been shown to exert
      antioxidant and anticancer effects, the anti-metastatic effects of beta-carotene
      on neuroblastoma cells remain poorly understood. The aim of the present study was
      to investigate the anti-metastatic effects of beta-carotene on highly malignant
      SK-N-BE(2)C neuroblastoma cells in vitro and in vivo. Treatment of SK-N-BE(2)C
      cells with beta-carotene was found to attenuate the migratory and invasive
      capabilities of the cells. In addition, the enzymatic activity and expression of
      matrix metalloproteinase (MMP)-2 was suppressed following beta-carotene treatment
      under both normoxia and hypoxia. To induce metastasis, immunodeficient nude mice
      were injected with SK-N-BE(2)C cells via the tail vein in vivo. The incidence of
      liver metastasis and mean tumor volume in mice that were administered beta
      carotene was decreased compared to controls. Furthermore, mRNA levels of MMPs,
      membrane-type (MT) 2 MMP and tissue inhibitors of metalloproteinases in liver
      tumor tissues were also lower following beta-carotene treatment. Level of hypoxia
      inducible factor-1alpha (HIF-1alpha) and its downstream targets, vascular
      endothelial growth factor and glucose transporter 1 (GLUT1), were lower both in
      vitro and in vivo following beta-carotene treatment. In conclusion, the present
      study provides the first evidence that beta-carotene may represent an effective
      chemotherapeutic agent by regulating the invasion and metastasis of neuroblastoma
      via HIF-1alpha. 

PMID- 24746830
TI  - Off-target effects of sulforaphane include the derepression of long terminal
      repeats through histone acetylation events.
AB  - Sulforaphane is a naturally occurring isothiocyanate in cruciferous vegetables.
      Sulforaphane inhibits histone deacetylases, leading to the transcriptional
      activation of genes including tumor suppressor genes. The compound has attracted
      considerable attention in the chemoprevention of prostate cancer. Here we tested
      the hypothesis that sulforaphane is not specific for tumor suppressor genes but
      also activates loci such as long terminal repeats (LTRs), which might impair
      genome stability. Studies were conducted using chemically pure sulforaphane in
      primary human IMR-90 fibroblasts and in broccoli sprout feeding studies in
      healthy adults. Sulforaphane (2.0 MUM) caused an increase in LTR transcriptional
      activity in cultured cells. Consumption of broccoli sprouts (34, 68 or 102 g) by
      human volunteers caused a dose dependent elevation in LTR mRNA in circulating
      leukocytes, peaking at more than a 10-fold increase. This increase in transcript
      levels was associated with an increase in histone H3 K9 acetylation marks in LTR
      15 in peripheral blood mononuclear cells from subjects consuming sprouts.
      Collectively, this study suggests that sulforaphane has off-target effects that
      warrant further investigation when recommending high levels of sulforaphane
      intake, despite its promising activities in chemoprevention. 

PMID- 24746831
TI  - Quercetin prevents ethanol-induced iron overload by regulating hepcidin through
      the BMP6/SMAD4 signaling pathway.
AB  - Emerging evidence has demonstrated that chronic ethanol exposure induces iron
      overload, enhancing ethanol-mediated liver damage. The purpose of this study was
      to explore the effects of the naturally occurring compound quercetin on ethanol
      induced iron overload and liver damage, focusing on the signaling pathway of the
      iron regulatory hormone hepcidin. Adult male C57BL/6J mice were pair-fed with
      isocaloric-Lieber De Carli diets containing ethanol (accounting for 30% of total
      calories) and/or carbonyl iron (0.2%) and treated with quecertin (100 mg/kg body
      weight) for 15 weeks. Mouse primary hepatocytes were incubated with ethanol (100
      mM) and quercetin (100 MUM) for 24 h. Mice exposed to either ethanol or iron
      presented significant fatty infiltration and iron deposition in the liver; these
      symptoms were exacerbated in mice cotreated with ethanol and iron. Quercetin
      attenuated the abnormity induced by ethanol and/or iron. Ethanol suppressed BMP6
      and intranuclear SMAD4 as well as decreased hepcidin expression. These effects
      were partially alleviated by quercetin supplementation in mice and hepatocytes.
      Importantly, ethanol caused suppression of SMAD4 binding to the HAMP promoter and
      of hepcidin messenger RNA expression. These effects were exacerbated by anti-BMP6
      antibody and partially alleviated by quercetin or human recombinant BMP6 in
      cultured hepatocytes. In contrast, co-treatment with iron and ethanol, especially
      exposure of iron alone, activated BMP6/SMAD4 pathway and up-regulated hepcidin
      expression, which was also normalized by quercetin in vivo. Quercetin prevented
      ethanol-induced hepatic iron overload different from what carbonyl iron diet
      elicited in the mechanism, by regulating hepcidin expression via the BMP6/SMAD4
      signaling pathway. 

PMID- 24746832
TI  - Fibrates and fish oil, but not corn oil, up-regulate the expression of the
      cholesteryl ester transfer protein (CETP) gene.
AB  - Cholesteryl ester transfer protein (CETP) is a plasma protein that reduces high
      density lipoprotein (HDL)-cholesterol (chol) levels and may increase
      atherosclerosis risk. n-3 and n-6 polyunsaturated fatty acids (PUFAs) are natural
      ligands, and fibrates are synthetic ligands for peroxisome proliferator activated
      receptor-alpha (PPARalpha), a transcription factor that modulates lipid
      metabolism. In this study, we investigated the effects of PUFA oils and fibrates
      on CETP expression. Hypertriglyceridemic CETP transgenic mice were treated with
      gemfibrozil, fenofibrate, bezafibrate or vehicle (control), and normolipidemic
      CETP transgenic mice were treated with fenofibrate or with fish oil (FO; n-3 PUFA
      rich), corn oil (CO, n-6 PUFA rich) or saline. Compared with the control
      treatment, only fenofibrate significantly diminished triglyceridemia (50%),
      whereas all fibrates decreased the HDL-chol level. Elevation of the CETP liver
      mRNA levels and plasma activity was observed in the fenofibrate (53%) and
      gemfibrozil (75%) groups. Compared with saline, FO reduced the plasma levels of
      nonesterified fatty acid (26%), total chol (15%) and HDL-chol (20%). Neither of
      the oil treatments affected the plasma triglyceride levels. Compared with saline,
      FO increased the plasma adiponectin level and reduced plasma leptin levels,
      whereas CO increased the leptin levels. FO, but not CO, significantly increased
      the plasma CETP mass (90%) and activity (23%) as well as increased the liver
      level of CETP mRNA (28%). In conclusion, fibrates and FO, but not CO, up
      regulated CETP expression at both the mRNA and protein levels. We propose that
      these effects are mediated by the activation of PPARalpha, which acts on a
      putative PPAR response element in the CETP gene. 

PMID- 24746833
TI  - High-fat diet increases tau expression in the brain of T2DM and AD mice
      independently of peripheral metabolic status.
AB  - Alzheimer's disease and type 2 diabetes mellitus are risk factors for each other.
      To investigate the effects of both genetic and high-fat-induced diabetic
      phenotype on the expression and exon 10 splicing of tau, we used the Alzheimer's
      disease mouse model (APdE9) cross-bred with the type 2 diabetes mouse model over
      expressing insulin-like growth factor 2 in the pancreas. High-fat diet,
      regardless of the genotype, significantly induced the expression of four repeat
      tau mRNA and protein in the temporal cortex of female mice. The mRNA levels of
      three repeat tau were also significantly increased by high-fat diet in the
      temporal cortex, although three repeat tau expression was considerably lower as
      compared to four repeat tau. Moreover, high-fat diet significantly increased the
      mRNA ratio of four repeat tau vs. three repeat tau in the temporal cortex of
      these mice. All of these effects were independent of the peripheral
      hyperglycemia, hyperinsulinemia and insulin resistance. Increased four repeat tau
      and three repeat tau levels significantly associated with impaired memory and
      reduced rearing in the female mice. High-fat diet did not affect
      neuroinflammation, Akt/GSK3beta signaling pathway or the expression of tau exon
      10 splicing enhancers in the temporal cortex. Our study suggests that the high
      fat diet independently of type 2 diabetes or Alzheimer's disease background
      induces the expression and exon 10 inclusion of tau in the brain of female mice. 

PMID- 24746834
TI  - Epigallocatechin gallate (EGCG) attenuates infrasound-induced neuronal impairment
      by inhibiting microglia-mediated inflammation.
AB  - Infrasound, a kind of common environmental noise and a major contributor of
      vibroacoustic disease, can induce the central nervous system (CNS) damage.
      However, no relevant anti-infrasound drugs have been reported yet. Our recent
      studies have shown that infrasound resulted in excessive microglial activation
      rapidly and sequential inflammation, revealing a potential role of microglia in
      infrasound-induced CNS damage. Epigallocatechin gallate (EGCG), a major bioactive
      component in green tea, has the capacity of protecting against various
      neurodegenerative diseases via an anti-inflammatory mechanism. However, it is
      still unknown to date whether EGCG acts on infrasound-induced microglial
      activation and neuronal damage. We showed that, after 1-, 2- or 5-day exposure of
      rats to 16 Hz, 130 dB infrasound (2 h/day), EGCG significantly inhibited
      infrasound-induced microglial activation in rat hippocampal region, evidenced by
      reduced expressions of Iba-1 (a marker for microglia) and proinflammatory
      cytokines (IL-1beta, IL-6, IL-18 and TNF-alpha). Moreover, infrasound-induced
      neuronal apoptosis in rat hippocampi was significantly suppressed by EGCG. EGCG
      also inhibited infrasound-induced activation of primary microglia in vitro and
      decreased the levels of proinflammatory cytokines in the supernatants of
      microglial culture, which were toxic to cultured neurons. Furthermore, EGCG
      attenuated infrasound-induced increases in nuclear NF-kappaB p65 and
      phosphorylated IkappaBalpha, and ameliorated infrasound-induced decrease in
      IkappaB in microglia. Therefore, our study provides the first evidence that EGCG
      acts against infrasound-induced neuronal impairment by inhibiting microglia
      mediated inflammation through a potential NF-kappaB pathway-related mechanism,
      suggesting that EGCG can be used as a promising drug for the treatment of
      infrasound-induced CNS damage. 

PMID- 24746835
TI  - Exposure to lard-based high-fat diet during fetal and lactation periods modifies
      breast cancer susceptibility in adulthood in rats.
AB  - The present study investigated whether early life exposure to high levels of
      animal fat increases breast cancer risk in adulthood in rats. Dams consumed a
      lard-based high-fat (HF) diet (60% fat-derived energy) or an AIN93G control diet
      (16% fat-derived energy) during gestation or gestation and lactation. Their 7
      week-old female offspring were exposed to 7,12-dimethyl-benzo[a]anthracene to
      induce mammary tumors. Pregnant dams consuming an HF diet had higher circulating
      leptin levels than pregnant control dams. However, compared to the control
      offspring, significantly lower susceptibility to mammary cancer development was
      observed in the offspring of dams fed an HF diet during pregnancy (lower tumor
      incidence, multiplicity and weight), or pregnancy and lactation (lower tumor
      multiplicity only). Mammary epithelial elongation, cell proliferation (Ki67) and
      expression of NFkappaB p65 were significantly lower and p21 expression and global
      H3K9me3 levels were higher in the mammary glands of rats exposed to an HF lard
      diet in utero. They also tended to have lower Rank/Rankl ratios (P=.09) and serum
      progesterone levels (P=.07) than control offspring. In the mammary glands of
      offspring of dams consuming an HF diet during both pregnancy and lactation, the
      number of terminal end buds, epithelial elongation and the BCL-2/BAX ratio were
      significantly lower and serum leptin levels were higher than in the controls. Our
      data confirm that the breast cancer risk of offspring can be programmed by
      maternal dietary intake. However, contrary to our expectation, exposure to high
      levels of lard during early life decreased later susceptibility to breast cancer.

PMID- 24746836
TI  - Reduced macrophage selenoprotein expression alters oxidized lipid metabolite
      biosynthesis from arachidonic and linoleic acid.
AB  - Uncontrolled inflammation is an underlying etiology for multiple diseases and
      macrophages orchestrate inflammation largely through the production of oxidized
      fatty acids known as oxylipids. Previous studies showed that selenium (Se) status
      altered the expression of oxylipids and magnitude of inflammatory responses.
      Although selenoproteins are thought to mediate many of the biological effects of
      Se, the direct effect of selenoproteins on the production of oxylipids is
      unknown. Therefore, the role of decreased selenoprotein activity in modulating
      the production of biologically active oxylipids from macrophages was
      investigated. Thioglycollate-elicited peritoneal macrophages were collected from
      wild-type and myeloid-cell-specific selenoprotein knockout mice to analyze
      oxylipid production by liquid chromatography/mass spectrometry as well as
      oxylipid biosynthetic enzyme and inflammatory marker gene expression by
      quantitative real-time polymerase chain reaction. Decreased selenoprotein
      activity resulted in the accumulation of reactive oxygen species, enhanced
      cyclooxygenase and lipoxygenase expression and decreased oxylipids with known
      anti-inflammatory properties such as arachidonic acid-derived lipoxin A4 (LXA4)
      and linoleic acid-derived 9-oxo-octadecadienoic acid (9-oxoODE). Treating RAW
      264.7 macrophages with LXA4 or 9-oxoODE diminished oxidant-induced macrophage
      inflammatory response as indicated by decreased production of TNFalpha. The
      results show for the first time that selenoproteins are important for the
      balanced biosynthesis of pro- and anti-inflammatory oxylipids during
      inflammation. A better understanding of the Se-dependent control mechanisms
      governing oxylipid biosynthesis may uncover nutritional intervention strategies
      to counteract the harmful effects of uncontrolled inflammation due to oxylipids.

PMID- 24746837
TI  - Extract of okra lowers blood glucose and serum lipids in high-fat diet-induced
      obese C57BL/6 mice.
AB  - Okra is an important tropical vegetable and source of dietary medicine. Here, we
      assayed the effects of an ethanol extract of okra (EO) and its major flavonoids
      isoquercitrin and quercetin 3-O-gentiobioside on metabolic disorders in high-fat
      diet-induced obese mouse. We found that treatment with EO, isoquercitrin and
      quercetin 3-O-gentiobioside reduced blood glucose and serum insulin levels and
      improved glucose tolerance in obese mice. Meanwhile, serum triglyceride levels
      and liver morphology in the mice were significantly ameliorated by EO and
      isoquercitrin treatment. Total cholesterol levels in isoquercitrin and quercetin
      3-O-gentiobioside treated mice were also reduced. We also found that EO inhibited
      the expression of nuclear receptor transcription factor PPARgamma, which is an
      important regulator of lipid and glucose homeostasis. Furthermore, we determined
      that EO and quercetin 3-O-gentiobioside have antioxidant activity in vitro. Our
      results indicate that okra may serve as a dietary therapy for hyperglycemia and
      hypertriglyceridemia. 

PMID- 24746838
TI  - Exposure to omega-3 fatty acids at early age accelerate bone growth and improve
      bone quality.
AB  - Omega-3 fatty acids (FAs) are essential nutritional components that must be
      obtained from foods. Increasing evidence validate that omega-3 FAs are beneficial
      for bone health, and several mechanisms have been suggested to mediate their
      effects on bone, including alterations in calcium absorption and urinary calcium
      loss, prostaglandin synthesis, lipid oxidation, osteoblast formation and
      inhibition of osteoclastogenesis. However, to date, there is scant information
      regarding the effect of omega-3 FAs on the developing skeleton during the rapid
      growth phase. In this study we aim to evaluate the effect of exposure to high
      levels of omega-3 FAs on bone development and quality during prenatal and early
      postnatal period. For this purpose, we used the fat-1 transgenic mice that have
      the ability to convert omega-6 to omega-3 fatty acids and the ATDC5 chondrogenic
      cell line as models. We show that exposure to high concentrations of omega-3 FAs
      at a young age accelerates bone growth through alterations of the growth plate,
      associated with increased chondrocyte proliferation and differentiation. We
      further propose that those effects are mediated by the receptors G-protein
      coupled receptor 120 (GPR120) and hepatic nuclear factor 4alpha, which are
      expressed by chondrocytes in culture. Additionally, using a combined study on the
      structural and mechanical bone parameters, we show that high omega-3 levels
      contribute to superior trabecular and cortical structure, as well as to stiffer
      bones and improved bone quality. Most interestingly, the fat-1 model allowed us
      to demonstrate the role of maternal high omega-3 concentration on bone growth
      during the gestation and postnatal period. 

PMID- 24746839
TI  - Proposing a Caco-2/HepG2 cell model for in vitro iron absorption studies.
AB  - The Caco-2 cell line is well established as an in vitro model for iron
      absorption. However, the model does not reflect the regulation of iron absorption
      by hepcidin produced in the liver. We aimed to develop the Caco-2 model by
      introducing human liver cells (HepG2) to Caco-2 cells. The Caco-2 and HepG2
      epithelia were separated by a liquid compartment, which allowed for epithelial
      interaction. Ferritin levels in cocultured Caco-2 controls were 21.7+/-10.3 ng/mg
      protein compared to 7.7+/-5.8 ng/mg protein in monocultured Caco-2 cells. The
      iron transport across Caco-2 layers was increased when liver cells were present
      (8.1%+/-1.5% compared to 3.5%+/-2.5% at 120 MUM Fe). Caco-2 cells were exposed to
      0, 80 and 120 MUM Fe and responded with increased hepcidin production at 120 MUM
      Fe (3.6+/-0.3 ng/ml compared to 2.7+/-0.3 ng/ml). The expression of iron exporter
      ferroportin in Caco-2 cells was decreased at the hepcidin concentration of 3.6
      ng/ml and undetectable at external addition of hepcidin (10 ng/ml). The apical
      transporter DMT1 was also undetectable at 10 ng/ml but was unchanged at the lower
      concentrations. In addition, we observed that sourdough bread, in comparison to
      heat-treated bread, increased the bioavailability of iron despite similar iron
      content (53% increase in ferritin formation, 97% increase in hepcidin release).
      This effect was not observed in monocultured Caco-2 cells. The Caco-2/HepG2 model
      provides an alternative approach to in vitro iron absorption studies in which the
      hepatic regulation of iron transport must be considered. 

PMID- 24746840
TI  - Interleukin-1alpha neutralisation in patients with cancer.

PMID- 24746841
TI  - MABp1, a first-in-class true human antibody targeting interleukin-1alpha in
      refractory cancers: an open-label, phase 1 dose-escalation and expansion study.
AB  - BACKGROUND: Inflammation is an important feature of the malignant phenotype and
      promotes angiogenesis, tumour invasiveness, metastases, and cachexia. We used a
      first-in-class, monoclonal antibody (MABp1) cloned from a human being to target
      interleukin-1alpha, a mediator of chronic inflammation. We aimed to assess the
      safety and tolerability of MABp1 for interleukin-1alpha blockade in a refractory
      cancer population. METHODS: We did an open-label, dose-escalation, and phase 1
      study of MABp1 in adults with metastatic cancer at the MD Anderson Clinical
      Center for Targeted Therapy (Houston, TX, USA). We used a standard 3+3 design to
      identify the maximum tolerated dose. Patients received MABp1 intravenously once
      every 3 weeks through four dose levels: 0.25 mg/kg, 0.75 mg/kg, 1.25 mg/kg, and
      3.75 mg/kg. After the dose-escalation phase, a second dosing arm was started with
      dosing every 2 weeks at the maximum tolerated dose. The primary objectives were
      safety, tolerability, characterisation of the pharmacokinetic profile, and
      identification of the recommended phase 2 dose. Secondary endpoints included
      pharmacodynamic effects and antitumour activity. All patients who received at
      least one dose of MABp1 were included in the safety analyses. This trial is
      registered with ClinicalTrials.gov, NCT01021072. FINDINGS: Between March 15,
      2010, and July 30, 2012, 52 patients with metastatic cancer (18 tumour types)
      received anti-interleukin-1alpha monotherapy in dose-escalation and expansion
      groups. MABp1 was well tolerated, with no dose-limiting toxicities or
      immunogenicity. Thus, the recommended phase 2 dose was concluded to be 3.75 mg/kg
      every 2 weeks. Pharmacokinetic data were consistent at all dose levels and showed
      no evidence of accumulation or increased clearance of MABp1 at increasing doses.
      For 42 assessable patients, median plasma interleukin-6 concentrations had
      decreased from baseline to week 8 by a median of 2.7 pg/mL (IQR -12.6 to 3.0;
      p=0.08). Of the 34 patients restaged, one patient had a partial response and ten
      had stable disease. 30 patients were assessable for change in lean body mass,
      which increased by a mean of 1.02 kg (SD 2.24; p=0.02) between baseline and week
      8. The most common adverse events possibly related to the study drug were
      proteinuria (n=11; 21%), nausea (7; 13%), and fatigue (7; 13%). The most frequent
      grade 3-4 adverse events (regardless of relation to treatment) were fatigue (3;
      6%), dyspnoea (2; 4%), and headache (2; 4%). Two patients (4%) had grade 5 events
      (death due to disease progression), which were unrelated to treatment.
      INTERPRETATION: MABp1 was well tolerated, no dose-limiting toxicities were
      experienced in this study, and disease control was observed. Further study of
      MABp1 anti-interleukin-1alpha antibody therapy for advanced stage cancer is
      warranted.

PMID- 24746843
TI  - Do Mechanical Devices Improve Return of Spontaneous Circulation Over Manual Chest
      Compressions in Out-of-Hospital Cardiac Arrest?
AB  - Data are inadequate to determine whether recent devices (either load-distributing
      band or piston-driven) confer benefit or harm, though early trial data suggest
      they do not.

PMID- 24746842
TI  - Simulation of planar soft tissues using a structural constitutive model: Finite
      element implementation and validation.
AB  - Computational implementation of physical and physiologically realistic
      constitutive models is critical for numerical simulation of soft biological
      tissues in a variety of biomedical applications. It is well established that the
      highly nonlinear and anisotropic mechanical behaviors of soft tissues are an
      emergent behavior of the underlying tissue microstructure. In the present study,
      we have implemented a structural constitutive model into a finite element
      framework specialized for membrane tissues. We noted that starting with a single
      element subjected to uniaxial tension, the non-fibrous tissue matrix must be
      present to prevent unrealistic tissue deformations. Flexural simulations were
      used to set the non-fibrous matrix modulus because fibers have little effects on
      tissue deformation under three-point bending. Multiple deformation modes were
      simulated, including strip biaxial, planar biaxial with two attachment methods,
      and membrane inflation. Detailed comparisons with experimental data were
      undertaken to insure faithful simulations of both the macro-level stress-strain
      insights into adaptations of the fiber architecture under stress, such as fiber
      reorientation and fiber recruitment. Results indicated a high degree of fidelity
      and demonstrated interesting microstructural adaptions to stress and the
      important role of the underlying tissue matrix. Moreover, we apparently resolve a
      discrepancy in our 1997 study (Billiar and Sacks, 1997. J. Biomech. 30 (7), 753
      756) where we observed that under strip biaxial stretch the simulated fiber splay
      responses were not in good agreement with the experimental results, suggesting
      non-affine deformations may have occurred. However, by correctly accounting for
      the isotropic phase of the measured fiber splay, good agreement was obtained.
      While not the final word, these simulations suggest that affine fiber kinematics
      for planar collagenous tissues is a reasonable assumption at the macro level.
      Simulation tools such as these are imperative in the design and simulation of
      native and engineered tissues. 

PMID- 24746844
TI  - Views of paramedics on their role in an out-of-hospital ambulance-based trial in
      ultra-acute stroke: qualitative data from the Rapid Intervention With Glyceryl
      Trinitrate in Hypertensive Stroke Trial (RIGHT).
AB  - STUDY OBJECTIVE: Optimal practices for recruiting, consenting, and randomizing
      patients, and delivering treatment in out-of-hospital ultra-acute stroke trials,
      remain unclear. We aim to identify key barriers and facilitators relevant to the
      design and conduct of ambulance-based stroke trials and to formulate preliminary
      recommendations for the design of future trials. METHODS: Using semistructured
      interviews, we investigated the experiences and challenges faced by paramedics
      who took part in a randomized controlled trial in suspected ultra-acute stroke,
      the Rapid Intervention With Glyceryl Trinitrate in Hypertensive Stroke Trial
      (RIGHT), in which recruitment, consent, randomization, assessment, and treatment
      were delivered by paramedics before hospitalization. RESULTS: We purposively
      selected a diversity sample of 14 of the 78 paramedics who participated in RIGHT.
      We identified 13 themes (7 facilitators and 6 barriers to out-of-hospital stroke
      research). A simple stroke diagnostic tool, use of proxy consent on behalf of
      patients, and straightforward trial processes were identified as the main
      facilitators. Recruitment became easier with each new randomization attempt. Key
      barriers reported were informed consent in the emergency setting, lack of
      institutional support for research, learning curve and rarity (each paramedic
      treats only a few eligible patients), and difficulty in attending training
      sessions. Interviewed paramedics were motivated to participate in research.
      CONCLUSION: Ultra-acute stroke research in the out-of-hospital environment is
      feasible, but important barriers need to be addressed. Proxy consent by
      paramedics addresses some of the difficulties with the consent process in the out
      of-hospital setting.

PMID- 24746845
TI  - Streetlights and quality measures for stroke.

PMID- 24746846
TI  - Looking through the retrospectoscope: reducing bias in emergency medicine chart
      review studies.

PMID- 24746847
TI  - Out-of-hospital stroke screen accuracy in a state with an emergency medical
      services protocol for routing patients to acute stroke centers.
AB  - STUDY OBJECTIVE: Emergency medical services (EMS) protocols, which route patients
      with suspected stroke to stroke centers, rely on the use of accurate stroke
      screening criteria. Our goal is to conduct a statewide EMS agency evaluation of
      the accuracies of the Cincinnati Prehospital Stroke Scale (CPSS) and the Los
      Angeles Prehospital Stroke Screen (LAPSS) for identifying acute stroke patients.
      METHODS: We conducted a retrospective study in North Carolina by linking a
      statewide EMS database to a hospital database, using validated deterministic
      matching. We compared EMS CPSS or LAPSS results (positive or negative) to the
      emergency department diagnosis International Classification of Diseases, Ninth
      Revision codes. We calculated sensitivity, specificity, and positive and negative
      likelihood ratios for the EMS diagnosis of stroke, using each screening tool.
      RESULTS: We included 1,217 CPSS patients and 1,225 LAPSS patients evaluated by
      117 EMS agencies from 94 North Carolina counties. Most EMS agencies contributing
      data had high annual patient volumes and were governmental agencies with
      nonvolunteer, emergency medical technician-paramedic service level providers. The
      CPSS had a sensitivity of 80% (95% confidence interval [CI] 77% to 83%) versus
      74% (95% CI 71% to 77%) for the LAPSS. Each had a specificity of 48% (CPSS 95% CI
      44% to 52%; LAPSS 95% CI 43% to 53%). CONCLUSION: The CPSS and LAPSS had similar
      test characteristics, with each having only limited specificity. Development of
      stroke screening scales that optimize both sensitivity and specificity is
      required if these are to be used to determine transport diversion to acute stroke
      centers.

PMID- 24746849
TI  - Diurnal salivary cortisol in relation to perceived stress at home and at work in
      healthy men and women.
AB  - This study investigated the association between diurnal salivary cortisol profile
      and perceived stress at work and at home. Healthy participants (N=180, 52% women)
      collected saliva cortisol samples immediately after waking up, 15 min later, 30
      min later, and at 9:00, 12:00, 15:00, 18:00 and 21:00. The area under the
      cortisol awakening curve with respect to ground (AUCgCAR) and increase (AUCiCAR),
      and diurnal slope between 9:00 and 21:00 were analyzed. Perceived stress at work
      and at home was measured with the Stress-Energy Questionnaire. Participants
      reporting stress at home had significantly lower AUCgCAR and a flatter diurnal
      slope. When performing separate analyses for men and women, this association was
      only significant among women. Perceived stress at work was not associated with
      any cortisol measure. This study highlights the importance of stress outside the
      workplace. The sex differences may indicate an increased vulnerability to non
      work stress in women.

PMID- 24746848
TI  - Fear conditioning and extinction across development: evidence from human studies
      and animal models.
AB  - The ability to differentiate danger and safety through associative processes
      emerges early in life. Understanding the mechanisms underlying associative
      learning of threat and safety can clarify the processes that shape development of
      normative fears and pathological anxiety. Considerable research has used fear
      conditioning and extinction paradigms to delineate underlying mechanisms in
      animals and human adults; however, little is known about these mechanisms in
      children and adolescents. The current paper summarizes the empirical data on the
      development of fear conditioning and extinction. It reviews methodological
      considerations and future directions for research on fear conditioning and
      extinction in pediatric populations. 

PMID- 24746850
TI  - Detection of Spiroplasma melliferum in honey bee colonies in the US.
AB  - Spiroplasma infections in honey bees have been reported in Europe and Asia quite
      recently, due to intensive studies on the epidemiology of honey bee diseases. The
      situation in the US is less well analyzed. Here, we examined the honey bee
      colonies in Beltsville, MD, where Spiroplasmamelliferum was originally reported
      and found S. melliferum infection in honey bees. Our data showed high variation
      of S. melliferum infection in honey bees with a peak prevalence in May during the
      course of one-year study period. The colony prevalence increased from 5% in
      February to 68% in May and then decreased to 25% in June and 22% in July. Despite
      that pathogenicity of spiroplasmas in honey bee colonies remains to be
      determined, our results indicated that spiroplasma infections need to be included
      for the consideration of the impacts on honey bee health. 

PMID- 24746851
TI  - A cocktail approach for assessing the in vitro activity of human cytochrome
      P450s: an overview of current methodologies.
AB  - An assessment of cytochrome P450 (CYP) enzyme activity is essential for
      characterizing the phase I metabolism of biological systems or to evaluate the
      inhibition/induction properties of xenobiotics. CYPs have generally been
      investigated individually by single probes, and metabolite formation has been
      monitored by liquid chromatography-mass spectrometry (LC-MS). To increase the
      throughput, many probes have been applied to assess multiple CYP activities
      simultaneously within a single experiment. This strategy is called the cocktail
      approach, and it has already been reviewed for in vivo applications, but never
      for in vitro ones. This review focuses for the first time on an in vitro cocktail
      approach, and it references the most notable articles on this topic. The
      advantages and limitations of applying cocktails for the in vitro activity
      assessment of major human CYPs, namely, CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9,
      CYP2C19, CYP2D6, CYP2E1 and subfamily CYP3A, are discussed. This article
      considers the probe reaction selections for each CYP according to regulatory
      recommendations, probe metabolic properties (i.e., specificity and turnover),
      probe concentrations and analytical sensitivity, but it also highlights a
      challenge specific to cocktail design, which is probe-probe interaction. The last
      part of the review reports some methodologies for incubating these cocktails and
      discusses some important issues regarding the incubation time, enzyme
      concentrations and sample preparation. 

PMID- 24746852
TI  - Human cytomegalovirus infection induces leukotriene B4 and 5-lipoxygenase
      expression in human placentae and umbilical vein endothelial cells.
AB  - INTRODUCTION: Human cytomegalovirus (HCMV) can cause congenital infection with
      risk of neurological disability. Maternal-fetal transmission is associated with
      placental inflammation. 5-lipoxygenase (5-LO) is the key enzyme in the
      biosynthesis of Leukotrienes (LTs), which are proinflammatory mediators. This
      study investigated the effect of HCMV infection on 5-LO expression and
      Leukotriene-B4 (LTB4) induction in human placentae and umbilical vein endothelial
      cells (HUVEC). METHODS: Seven placentae from fetuses with congenital HCMV
      infection and brain damage and six controls were stained with HCMV-immediate
      early-antigen (HCMV-IEA) and 5-LO by immunohistochemistry. 5
      hydroxyeicosatetraenoic acid (5-HETE) and LTB4 were measured in culture
      supernatant from ex vivo HCMV-infected placental histocultures by liquid
      chromatography. In vitro, HCMV infected HUVEC cells were analyzed for 5-LO mRNA
      and protein expression by real time PCR and immunofluorescence staining. RESULTS:
      HCMV-IEA was abundant in all HCMV infected placentae but absent in control
      placentae. 5-LO expression was higher in endothelial and smooth muscle cells of
      HCMV-infected placentae, compared to control placentae. HCMV infection induced an
      up-regulation of LTB4 in ex vivo placental explants with higher levels of LTB4 at
      72 h compared to controls (p = 0.002). In vitro, 5-LO transcript and protein
      expression were significantly induced in HCMV-infected HUVEC, compared to the
      control cultures (p = 0.036). CONCLUSION: The presence of HCMV coincided with
      high 5-LO expression in cells of in vivo HCMV infected placentae. HCMV induced up
      regulation of 5-LO in both ex vivo HCMV-infected placental explants and HUVEC.
      HCMV induced LT-biosynthesis in congenitally infected placentae may have a role
      in pathogenesis of congenital HCMV disease.

PMID- 24746853
TI  - Gastrocnemius inflexibility on foot progression angle and ankle kinetics during
      walking.
AB  - BACKGROUND: Gastrocnemius inflexibility is a major problem in many orthopedic and
      neurological patients. Clinically, inflexible gastrocnemius muscles interfere
      with the performance of functional abilities and associate with many overuse
      injuries of the lower extremity. The purpose of this study was to investigate the
      effects of the gastrocnemius inflexibility on the foot progression angle and
      ankle kinetics during walking. METHODS: There were 50 subjects, 23 patients with
      the inflexible gastrocnemius and 27 normal subjects, included in this
      investigation. Participants were asked to walk at two preset cadences of 100
      steps/min and 140 steps/min. Data were collected from a motion analysis system
      and force plates. Kinematic and kinetic variables of gait were computed and
      analyzed. FINDINGS: Compared with the control group, greater toe-out foot
      progression angle (P=0.001, effect size=0.314) and knee external rotation
      (P=0.008, effect size=0.136) were found in the inflexible group during stance
      phase. Furthermore, significant greater plantarflexion moment (P=0.032, effect
      size=0.093) and medial ground reaction force (P=0.009, effect size=0.135) during
      midstance were discovered in the inflexible group. INTERPRETATION: The present
      results indicate that gastrocnemius inflexibility might bring about the changes
      in the joint angles, ankle moments and ground reaction forces. The abnormal joint
      alignment in the lower extremities and greater force upon joint tissue might be
      significant for the clinical considerations on soft tissue injuries for the
      patients with inflexible gastrocnemius muscles.

PMID- 24746855
TI  - The beneficial effect of a prolyl oligopeptidase inhibitor, KYP-2047, on alpha
      synuclein clearance and autophagy in A30P transgenic mouse.
AB  - The misfolding and aggregation of alpha-synuclein (aSyn) eventually lead to an
      accumulation of toxic forms that disturb normal neuronal function and result in
      cell death. aSyn rich inclusions are seen in Parkinson's disease, dementia with
      Lewy bodies and other synucleinopathies. Prolyl oligopeptidase (PREP) can
      accelerate the aggregation process of aSyn and the inhibition of PREP leads to a
      decreased amount of aggregated aSyn in cell models and in aSyn transgenic mice.
      In this study, we investigated the effect of 5- and 28-day PREP inhibitor (KYP
      2047) treatments on a mouse strain carrying a point mutation in the aSyn coding
      gene. Following PREP inhibition, we found a decrease in high molecular-weight
      oligomeric aSyn and a concomitant increase in the amount of the autophagosome
      marker, LC3BII, suggesting enhanced macroautophagy (autophagy) and aSyn clearance
      by KYP-2047. Moreover, 28-day treatment with KYP-2047 caused significant
      increases in striatal dopamine levels. In cell culture, overexpression of PREP
      reduced the autophagy. Furthermore, the inhibition of PREP normalized the changes
      on autophagy markers (LC3BII and p62) caused by an autophagy inhibition or aSyn
      overexpression, and induced the expression of beclin 1, a positive regulator of
      autophagy. Taken together, our results suggest that PREP inhibition accelerates
      the clearance of protein aggregates via increased autophagy and thus normalizes
      the cell functions in vivo and in vitro. Therefore, PREP inhibition may have
      future potential in the treatment of synucleinopathies. 

PMID- 24746854
TI  - Clinically-relevant measures associated with altered contact forces in patients
      with anterior cruciate ligament deficiency.
AB  - BACKGROUND: Knee joint contact forces are altered after anterior cruciate
      ligament injury during walking and may be related to clinically-relevant measures
      of impairments or self-reported function. The purpose of this study was to
      investigate the association of several clinically-relevant measures with altered
      knee contact forces in patients with anterior cruciate ligament injury. METHODS:
      Data for this study represent a cross-sectional observational analysis of thirty
      seven (23 M, 14 F) patients with complete unilateral anterior cruciate ligament
      injury. Gait analysis with electromyography was used to obtain estimates of
      tibiofemoral joint contact force using an electromyography-driven musculoskeletal
      model. Multivariable linear regression was used to identify measures associated
      with tibiofemoral joint contact force. FINDINGS: Involved knee extensor muscle
      strength and patient-reported knee function on the Global Rating Scale of
      perceived function were significantly associated with peak tibiofemoral contact
      force for the involved limb. Patients who were stronger and who perceived higher
      knee function walked with greater contact forces on their involved knees. After
      controlling for walking speed, involved extensor strength explained 8.9% of the
      variance in involved peak tibiofemoral contact force and score on the Global
      Rating Scale explained an additional 9.4% of the variance. INTERPRETATION:
      Improvements in involved quadriceps strength and overall function as measured by
      patient self-report may be important for increasing involved limb contact forces,
      thereby restoring loading symmetry in these patients who demonstrate decreased
      involved limb loading after injury. These results highlight the potential value
      of studying the recovery of strength, self-reported function and joint loading
      symmetry in patients with anterior cruciate ligament injury.

PMID- 24746856
TI  - Ischemic insults induce necroptotic cell death in hippocampal neurons through the
      up-regulation of endogenous RIP3.
AB  - Global cerebral ischemia induces selective acute neuronal injury of the CA1
      region of the hippocampus. The type of cell death that ensues may include
      different programmed cell death mechanisms namely apoptosis and necroptosis, a
      recently described type of programmed necrosis. We investigated whether
      necroptosis contributes to hippocampal neuronal death following oxygen-glucose
      deprivation (OGD), an in vitro model of global ischemia. We observed that OGD
      induced a death receptor (DR)-dependent component of necroptotic cell death in
      primary cultures of hippocampal neurons. Additionally, we found that this
      ischemic challenge upregulated the receptor-interacting protein kinase 3 (RIP3)
      mRNA and protein levels, with a concomitant increase of the RIP1 protein.
      Together, these two related proteins form the necrosome, the complex responsible
      for induction of necroptotic cell death. Interestingly, we found that caspase-8
      mRNA, a known negative regulator of necroptosis, was transiently decreased
      following OGD. Importantly, we observed that the OGD-induced increase in the RIP3
      protein was paralleled in an in vivo model of transient global cerebral ischemia,
      specifically in the CA1 area of the hippocampus. Moreover, we show that the
      induction of endogenous RIP3 protein levels influenced neuronal toxicity since we
      found that RIP3 knock-down (KD) abrogated the component of OGD-induced necrotic
      neuronal death while RIP3 overexpression exacerbated neuronal death following
      OGD. Overexpression of RIP1 also had deleterious effects following the OGD
      challenge. Taken together, our results highlight that cerebral ischemia activates
      transcriptional changes that lead to an increase in the endogenous RIP3 protein
      level which might contribute to the formation of the necrosome complex and to the
      subsequent component of necroptotic neuronal death that follows ischemic injury. 

PMID- 24746858
TI  - Kikuchi disease presenting with aseptic meningitis.
AB  - Kikuchi disease is a self-limited disease characterized primarily by regional
      lymphadenopathy. Kikuchi disease was first described in 1972 as a lymphadenitis
      with specific histopathologic findings. Extranodal manifestations have been
      reported, including rare neurologic complications such as aseptic meningitis.
      This case report discusses a patient who presented to the ED with signs and
      symptoms suggestive of aseptic meningitis and was ultimately diagnosed with
      Kikuchi disease. We also review the epidemiology, clinical presentation, and
      laboratory findings typically found in patients with Kikuchi disease. Inclusion
      of Kikuchi disease in the differential diagnosis for meningitis may help
      establish a diagnosis in patients also presenting with regional lymphadenopathy.

PMID- 24746859
TI  - Choloperitoneum causes extensive coloring of the abdominal wall skin.
AB  - Laparoscopic cholecystectomy, because it is the less invasive surgical procedure,
      has been established as the procedure of choice for the treatment of patients
      with symptomatic gallbladder stones. However, bile leakage after laparoscopic
      cholecystectomy should not be overlooked. It is generally due to a minor biliary
      complication, although it can sometimes herald a major duct injury. Bile leakage
      rates of 1.2% to 4.0% in laparoscopic cholecystectomies have been reported, which
      are higher than the incidence with open cholecystectomies.

PMID- 24746857
TI  - Alzheimer's and ABC transporters--new opportunities for diagnostics and
      treatment.
AB  - Much has been said about the increasing number of demented patients and the main
      risk factor 'age'. Frustratingly, we do not know the precise pattern and all
      modulating factors that provoke the pathologic changes in the brains of affected
      elderly. We have to diagnose early to be able to stop the progression of diseases
      that irreversibly destroy brain substance. Familiar AD cases have mislead some
      researchers for almost 20 years, which has unfortunately narrowed the scientific
      understanding and has, thus, lead to insufficient funding of independent
      approaches. Therefore, basic researchers hardly have been able to develop
      causative treatments and clinicians still do not have access to prognostic and
      early diagnostic tools. During the recent years it became clear that insufficient
      Abeta export, physiologically facilitated by the ABC transporter superfamily at
      the brain's barriers, plays a fundamental role in disease initiation and
      progression. Furthermore, export mechanisms that are deficient in affected
      elderly are new targets for activation and, thus, treatment, but ideally also for
      prevention. In sporadic AD disturbed clearance of beta-amyloid from the brain is
      so far the most important factor for its accumulation in the parenchyma and
      vessel walls. Here, we review findings about the contribution of ABC transporters
      and of the perivascular drainage/glymphatic system on beta-amyloid clearance. We
      highlight their potential value for innovative early diagnostics using PET and
      describe recently described, effective ABC transporter-targeting agents as
      potential causative treatment for neurodegenerative proteopathies/dementias.

PMID- 24746860
TI  - Clinical evaluation compared to the pulse indicator continuous cardiac output
      system in the hemodynamic assessment of critically ill patients.
AB  - OBJECTIVE: The objective was to assess the effects of pulse indicator continuous
      cardiac output catheterization on the management of critically ill patients and
      the alteration of therapy in intensive care units. METHODS: One hundred thirty
      two patients with primary physiological abnormalities of hypotension or hypoxemia
      were evaluated. Prior to catheterization, physicians were asked to complete a
      questionnaire that collected information regarding predictions of the ranges of
      several hemodynamic variables and plans for therapy. After catheterization, each
      chart was reviewed by a panel of intensive care attending physicians to determine
      the possibility of altering the therapy. RESULTS: Overall correct classification
      of the key variables ranged from 46.0% to 65.4%. Catheterization results prompted
      alterations in therapy for 45.5% of patients. The fellows were less accurate in
      predicting hemodynamic values for patients whose diagnoses were unknown, and the
      primary abnormality was hypotension. There was significant difference in the
      physicians' abilities to predict the hemodynamics for the subgroups with and
      without acute myocardial infarction. When the patients were divided into 3
      subgroups by Acute Physiology and Chronic Health Evaluation II and Sepsis-related
      Organ Failure Assessment scores, the fellows had the most difficulty predicting
      the variables of the moderately ill patients in the middle subgroup, which led to
      the greatest percentage of therapy alterations for this subgroup; and this
      difference was significant. CONCLUSIONS: The hemodynamic variables obtained from
      pulse indicator continuous cardiac output catheterization improved the accuracy
      of bedside evaluations and led to alterations in therapeutic plans, particularly
      among the moderately ill patients with hypotension or unknown diagnoses.

PMID- 24746861
TI  - A comparison of implanted cardioverter/defibrillator interrogation protocol
      effectiveness between 2 patients in the ED.

PMID- 24746862
TI  - Integrating place into research on drug use, drug users' health, and drug policy.

PMID- 24746863
TI  - Preferences for policy options for cannabis in an Australian general population:
      A discrete choice experiment.
AB  - BACKGROUND: Policy choices for illicit drugs such as cannabis entail
      consideration of competing factors such as individual health, societal views
      about pleasure, and criminal justice impacts. Society must weigh up these factors
      in determining the preferred cannabis policy; although often cast as a contest
      between legalisation of cannabis or full prohibition the actual policy choices
      are not so black and white. This study assessed societal preferences for
      different cannabis policies and multiple consequences. METHOD: A discrete choice
      experiment (DCE) quantified value-based preferences for alternative cannabis
      policies described by the five key attributes legal status, health harms,
      criminal justice service costs, rates of cannabis use and purchase location. An
      online survey was conducted on a population sample of 1020 Australians. The
      analytical model was based on stated choices for Policy A, B or Current Policy.
      RESULTS: The results revealed a strong general preference for either civil
      penalties or legalisation compared to cannabis cautioning (Current Policy) and a
      strong dislike of criminalising possession and use of cannabis. Results also
      demonstrate difference in preferences among those with different demographics and
      beliefs. Understanding these nuances help to quantify the range of preferences
      held within the population and can be used to inform policy. CONCLUSION: This is
      the first known DCE survey applied to the area of illicit drugs policy. It
      demonstrates the public hold disparate views on the most appropriate status for
      cannabis offences and they are able to make trade-offs between policy choices and
      outcomes in complex areas of social policy.

PMID- 24746864
TI  - Feasibility of MRI and selection of adequate region of interest for longitudinal
      studies of growth and fatness in swine models of obesity.
AB  - PURPOSES: To determine the feasibility of MRI for imaging subcutaneous and
      visceral adiposity in longitudinal studies in obese swine models (Iberian pig).
      To establish the anatomical regions of interest (ROIs) and measurement points
      (MPs) adequate for their evaluation through analyses on the inter-individual
      variability and over-time reproducibility and through the assessment of their
      reliability and validity by comparison with in vivo and ex vivo zoometric data.
      MATERIAL AND METHODS: Five male and five female pigs were used from four (live
      weight around 48 kg and back-fat depth around 18 mm) to eight months old (live
      weight 134 kg and back-fat depth around 48 mm). MRI was carried out with a
      Panorama 0.23T scanner (Philips Medical Systems, Best, Netherlands), using a
      body/spine XL coil. RESULTS: The ROIs of election for visualization of
      subcutaneous data are located from the cranial margin of left diaphragmatic crura
      to the lumbar vertebrae L3. Visceral adiposity may be equally evaluated from the
      vertebrae L1 to L3. CONCLUSIONS: MRI allows the evaluation of subcutaneous and
      visceral fatness in a single acquisition, which improves animal welfare and time-
      and cost-efficiency and provides an accurate, consistent and repeatable procedure
      for sequential studies of adiposity in obese swine.

PMID- 24746866
TI  - The hand in systemic diseases other than rheumatoid arthritis.
AB  - This review outlines the skin, vascular and musculoskeletal symptoms affecting
      the hand during systemic inflammatory diseases other than rheumatoid arthritis.
      Skin lesions are diagnosed clinically and their symptomatology is documented
      through an extensive series of photographs. These conditions may require specific
      care before a surgical procedure can be performed. Vascular lesions are also
      diagnosed clinically and their symptomatology is described in detail. It is
      important to recognize that acrocyanosis is always benign. The surgeon should be
      able to distinguish between primary, but benign Raynaud's disease and secondary
      Raynaud's syndrome, which has a high risk of finger necrosis. Current
      preventative and curative treatments for finger necrosis are described. The
      clinical, radiological, progressive and therapeutic features of musculoskeletal
      lesions are reviewed, namely those associated with psoriatic arthritis, systemic
      sclerosis and lupus. 

PMID- 24746865
TI  - Direct transcatheter aortic valve implantation with self-expandable
      bioprosthesis: feasibility and safety.
AB  - BACKGROUND: Balloon valvuloplasty has been considered a mandatory step of the
      transcatheter aortic valve implantation (TAVI), although it is not without risk.
      The aim of this work was to evaluate the feasibility and safety of TAVI performed
      without pre-dilation (direct TAVI) of the stenosed aortic valve. MATERIAL AND
      METHODS: Between June 2012 and June 2013, 55 consecutive TAVI performed without
      pre-dilation at our institution using the self-expandable CoreValve prosthesis
      (Medtronic, Minneapolis, MN) were analyzed and compared with 45 pre-dilated TAVI
      performed the previous year. Inclusion criteria were a symptomatic and severe
      aortic stenosis. Exclusion criteria were defined as presence of pure aortic
      regurgitation, degenerated surgical bioprosthesis or bicuspid aortic valve and
      prior procedure of balloon aortic valvuloplasty performed as a bridge to TAVI.
      RESULTS: High-burden calcification in the device landing zone, assessed by CT
      scan, was found in most of the patients. The valve size implanted was similar in
      both groups. Device success was higher in direct TAVI (85%vs.64%,p=0.014), mostly
      driven by a significant lower incidence of paravalvular leak
      (PVL>=2;9%vs.33%,p=0.02). Safety combined end point at 30 days was similar in
      both groups. CONCLUSION: Compared to TAVI with pre-dilation, direct TAVI is
      feasible regardless of the presence of bulky calcified aortic valve and the valve
      size implanted. Device success was higher in direct TAVI, mostly driven by a
      lower incidence of paravalvular leak. Safety at 30 days was similar in two
      groups.

PMID- 24746867
TI  - Preemies to preschoolers: tubing tiny tots and trauma FAQs, part 2.

PMID- 24746868
TI  - Analysis of emergency medical services triage and dispatch errors by registered
      nurses in Italy.
AB  - INTRODUCTION: The major elements of an effective emergency medical services (EMS)
      system include a single telephone access number, accurate assessment of the
      urgency of the health problem, and timely dispatch of appropriate personnel and
      equipment. In Italy, EMS calls are managed by emergency operations centers by
      registered nurses who have received specialized education in this function. The
      nurses determine the criticality of the situations and assign an EMS response
      priority level identified by a color code, ranging from red (very critical) to
      green (not critical). At times, the severity of a situation may be
      underestimated, resulting in assignment of a lower EMS response priority and the
      potential for patient death (code black). The purpose of this study was to
      analyze factors associated with registered nurse under-triage of EMS calls
      subsequently found to be associated with deaths, termed "green-black code" cases.
      METHODS: We carried out a retrospective qualitative analysis of EMS telephone
      conversations using Fele's conversation analysis method. The characteristics of
      green-black code calls were compared with the characteristics of the population
      of all EMS calls during the study period. RESULTS: The study patients were older,
      with a mean age of 81.6 years. The callers were individuals calling on behalf of
      the patients, rather than the patients themselves. The callers reported symptoms
      that were not life-threatening. Nurse operators did not always inquire about the
      patients' vital signs as required by the Medical Priority Dispatch System
      protocol. The phone conversations were shorter than normal (54.26 seconds vs 65
      seconds). DISCUSSION: Although the importance of dispatch system protocols is
      wellknown, it is also important that nurse triage operators have proper training
      to ensure that major parameters such as vital signs and symptomatology are
      obtained and to reduce caller stress level.

PMID- 24746869
TI  - Blood group genotyping for patients with autoimmune hemolytic anemia.

PMID- 24746871
TI  - Differences in cerebrospinal fluid inflammatory cell reaction of patients with
      leptomeningeal involvement by lymphoma and carcinoma.
AB  - Dissemination of neoplastic cells into the cerebrospinal fluid (CSF) and
      leptomeninges is a devastating complication in patients with epithelial cell
      neoplasia (leptomeningeal carcinomatosis [LC]) and lymphomas (lymphomatous
      meningitis [LyM]). Information about the surrounding inflammatory cell
      populations is scarce. In this study, flow cytometry immunophenotyping was used
      to describe the distribution of the main leukocyte populations in the CSF of 83
      patients diagnosed with neoplastic meningitis (LC, n = 65; LyM, n = 18). These
      data were compared with those obtained in the CSF from 55 patients diagnosed with
      the same groups of neoplasia without meningeal involvement (solid tumors, n = 36;
      high-grade lymphoma, n = 19). Median (interquartile) rates of lymphocytes,
      monocytes, and polymorphonuclear (PMN) cells were 59.7% (range, 35-76.6%), 24%
      (range, 16-53%), and 1.5% (range, 0-7.6%) in LC, respectively, and 98.5% (range,
      70.8-100%), 1.5% (range, 0-29.3%), and 0% in LyM, respectively (P < 0.001). No
      difference was observed between patients with breast adenocarcinoma (n = 30) and
      lung adenocarcinoma (n = 21), nor with different rates of malignant CSF
      involvement. Patients with lymphoma (with or without LyM) had a similar CSF
      leukocyte distribution, but cancer patients with LC and without LC had a
      distinctive PMN cell rate (P = 0.002). These data show that CSF samples from
      patients with LC have a greater number of inflammatory cells and a different
      leukocyte distribution than seen in the CSF from patients with LyM. Description
      of PMN cells is a distinctive parameter of patients with LC, compared with the
      CSF from patients with LyM and patients with cancer but without LC.

PMID- 24746872
TI  - Optimization of a sample preparation method for multiresidue analysis of
      pesticides in tobacco by single and multi-dimensional gas chromatography-mass
      spectrometry.
AB  - A selective and sensitive multiresidue analysis method, comprising 4 7pesticides,
      was developed and validated in tobacco matrix. The optimized sample preparation
      procedure in combination with gas chromatography mass spectrometry in selected
      ion-monitoring (GC-MS/SIM) mode offered limits of detection (LOD) and
      quantification (LOQ) in the range of 3-5 and 7.5-15ng/g, respectively, with
      recoveries between 70 and 119% at 50-100ng/g fortifications. In comparison to the
      modified QuEChERS (Quick-Easy-Cheap-Effective-Rugged-Safe method: 2g tobacco+10ml
      water+10ml acetonitrile, 30min vortexing, followed by dispersive solid phase
      extraction cleanup), the method performed better in minimizing matrix co
      extractives e.g. nicotine and megastigmatrienone. Ambiguity in analysis due to co
      elution of target analytes (e.g. transfluthrin-heptachlor) and with matrix co
      extractives (e.g. delta-HCH-neophytadiene, 2,4-DDE-linolenic acid) could be
      resolved by selective multi-dimensional (MD)GC heart-cuts. The method holds
      promise in routine analysis owing to noticeable efficiency of 27
      samples/person/day. 

PMID- 24746870
TI  - Epigenetics of idiopathic pulmonary fibrosis.
AB  - Idiopathic pulmonary fibrosis (IPF) is a complex lung disease of unknown
      etiology. Development of IPF is influenced by both genetic and environmental
      factors. Recent work by our and other groups has identified strong genetic
      predisposition factors for the development of pulmonary fibrosis, and cigarette
      smoke remains the most strongly associated environmental exposure risk factor.
      Gene expression profiling studies of IPF lung have taught us quite a bit about
      the biology of this fatal disease, and those of peripheral blood have provided
      important biomarkers. However, epigenetic marks may be the missing link that
      connects the environmental exposure in genetically predisposed individuals to
      transcriptional changes associated with disease development. Moreover, epigenetic
      marks represent a promising therapeutic target for IPF. In this review, the
      disease is introduced, genetic and gene expression studies in IPF are summarized,
      exposures relevant to IPF and known epigenetic changes associated with cigarette
      smoke exposure are discussed, and epigenetic studies conducted so far in IPF are
      summarized. Limitations, challenges, and future opportunities in this field are
      also discussed. 

PMID- 24746873
TI  - Editor's Choice - Endovascular aneurysm repair versus open repair for patients
      with a ruptured abdominal aortic aneurysm: a systematic review and meta-analysis
      of short-term survival.
AB  - BACKGROUND: There is clinical equipoise between open (OR) and endovascular
      aneurysm repair (EVAR) for the best treatment of ruptured abdominal aortic
      aneurysm (RAAA). OBJECTIVE: The aim of the study was to perform a systematic
      review and meta-analysis to estimate the short-term (combined 30-day or in
      hospital) survival after EVAR and OR for patients with RAAA. Data sources
      included Medline, Embase, and the World Health Organization International
      Clinical Trials Registry until 13 January 2014. All randomised controlled trials
      (RCTs), observational cohort studies, and administrative registries comparing OR
      and EVAR of at least 50 patients were included. Articles were full-length and in
      English. METHODS: Standard PRISMA guidelines were followed. The methodological
      quality of RCTs was assessed with the Cochrane Collaboration's tool for assessing
      risk of bias. The quality of observational studies was assessed with a modified
      Cochrane Collaboration's tool for assessing risk of bias, the Newcastle-Ottawa
      Scale, and the Methodological Index for Non-Randomized Studies. The results of
      the RCTs, of the obersvational studies, and of the administrative registries were
      pooled separately and analysed with the use of a random effects model. RESULTS:
      From a total of 3,769 articles, three RCTs, 21 observational studies, and eight
      administrative registries met the inclusion criteria. In the RCTs, the risk of
      bias was lowest and the pooled odds ratio for death after EVAR versus OR was 0.90
      (95% CI 0.65-1.24). The majority of the observational studies had a high risk of
      bias and the pooled odds ratio for death was 0.44 (95% CI 0.37-0.53). The
      majority of the administrative registries had a high risk of bias and the pooled
      odds ratio for death was 0.54 (95% CI 0.47-0.62). CONCLUSION: Endovascular
      aneurysm repair is not inferior to open repair in patients with a ruptured
      abdominal aortic aneurysm. This supports the use of EVAR in suitable patients and
      OR as a reasonable alternative.

PMID- 24746874
TI  - From genome-wide association study hits to new insights into experimental
      hematology.
AB  - Despite significant improvements in our knowledge of the mechanisms of normal and
      pathological hematopoiesis, our current understanding is most likely an
      oversimplification of the complexity of regulatory networks at play. Thus,
      considerable efforts have been made to catalogue the total sum of germline
      alterations in individual genomes affecting human hematopoiesis. These efforts
      ultimately led to the discovery of a large number of new genes not previously
      implicated in blood formation. Although identification of novel genes is
      important in revealing the profiles of genetic variations associated with normal
      hematopoiesis, further functional studies are necessary to improve our
      understanding of the mechanism(s) involved in these processes. In this review, we
      summarize the knowledge gained from genome-wide association studies to elucidate
      the relationship between genetics and blood cell traits. We discuss the most
      important recent advances, with an emphasis on functional follow-up studies that
      have been particularly useful in providing an insight into novel regulatory
      processes that influence blood cell formation and function. We also discuss
      potential future directions and challenges in the field. 

PMID- 24746875
TI  - Expression profiling of leukemia patients: key lessons and future directions.
AB  - Gene expression profiling (GEP) is a well-established indispensable tool used to
      study hematologic malignancies, including leukemias. Here, we summarize the
      insights into the molecular basis of leukemias obtained by means of GEP, focusing
      especially on acute myeloid leukemia (AML), one of the first diseases to be
      extensively studied by GEP. Profiling mRNA and microRNA expression are discussed
      in view of their applicability to class prediction, class discovery, and
      comparison, as well as outcome prediction, and special attention is paid to the
      recent advances in our understanding of the role of alternative RNA splicing in
      AML. In addition to microarray-based GEP approaches, over the last few years RNA
      sequencing based on next-generation sequencing technology is gaining wider
      recognition as an advanced tool for transcriptome profiling. Therefore, the
      advantages of RNA sequencing-based GEP and its current and potential implications
      in AML are discussed. Finally, we also highlight recent efforts to integrate
      already available and newly acquired omics data sets so that a more precise
      understanding of AML biology and clinical behavior can be achieved, which
      ultimately will contribute to further refine leukemia management. 

PMID- 24746876
TI  - Optimizing reporter constructs for in vivo bioluminescence imaging of interferon
      gamma stimulated mesenchymal stromal cells.
AB  - Mesenchymal stromal cells (MSCs) are a promising treatment modality for a variety
      of diseases. Strategies to investigate the fate of MSCs in vivo are important to
      unravel their therapeutic mechanisms. However, currently available techniques are
      hampered by their low sensitivity. We therefore aimed to optimize in vivo
      bioluminescence imaging of MSCs. We compared MSCs transduced with firefly
      luciferase (Fluc) and transmembrane-bound Gaussia luciferase driven by the human
      cytomegalovirus, spleen focus-forming virus (SFFV), and elongation factor 1-alpha
      (EF1alpha) promoters. Although cytomegalovirus-transmembrane-bound Gaussia
      luciferase-transduced MSCs showed the highest light intensity in vitro, the
      signal was almost undetectable in vivo. Spleen focus-forming virus-Fluc
      transduced MSCs revealed a bright signal in vivo, but transgene expression was
      silenced upon in vitro stimulation with interferon (IFN)-gamma. Therefore, the
      SFFV promoter was replaced by the EF1alpha promoter. Light emission of Fluc under
      the control of EF1alpha was similar to SFFV-Fluc. Although EF1alpha-Fluc light
      emission was decreased tenfold in the presence of IFN-gamma when compared with
      unstimulated MSCs, the bioluminescent signal could still be detected and was
      clearly distinguishable from untransduced MSCs. Furthermore, stimulation of MSCs
      with tumor necrosis factor-alpha hardly affected transgene expression in EF1alpha
      Fluc-transduced MSCs. Thus, the use of the EF1alpha promoter partially overcomes
      silencing and allows in vivo bioluminescence imaging of IFN-gamma-stimulated
      MSCs.

PMID- 24746877
TI  - What are we and what do we expect to become?

PMID- 24746878
TI  - Why are there no good treatments for diabetic neuropathy?

PMID- 24746880
TI  - Decreasing need for artificial urinary sphincter revision surgery by precise cuff
      sizing in men with spongiosal atrophy.
AB  - PURPOSE: Many patients with persistent incontinence after an artificial urinary
      sphincter procedure gain improved continence after cuff downsizing. In 2010 a
      new, smaller (3.5 cm) artificial urinary sphincter cuff was introduced. We
      hypothesized that men with spongiosal atrophy previously treated with a 4.0 cm
      cuff would now show a decreased rate of revision surgery due to more accurate
      cuff sizing. MATERIALS AND METHODS: We evaluated the outcome in men who received
      identical 4.0 cm cuff sizes in 2 eras, before (2007 to 2009) and after (2010 to
      2013) the introduction of the 3.5 cm artificial urinary sphincter cuff. Patients
      with a history of cuff erosion or those undergoing tandem, transcorporal, or 4.5
      cm or greater cuff placement were excluded from analysis. We validated our
      institutional results using the nationwide AMS(r) PIF (Patient Information Form)
      database from identical time frames. RESULTS: Of 236 men who underwent artificial
      urinary sphincter placement at our institution during the study period 170 with a
      mean age of 67 years met study inclusion criteria, of whom 88 (52%) received a
      4.0 cm artificial urinary sphincter cuff. Mean followup was 34 months. Ten of 45
      patients (22.2%) who had a 4.0 cm cuff placed from 2007 to 2009 required cuff
      downsizing for persistent incontinence while only 2 of 43 (4.7%) who received a
      4.0 cm cuff from 2010 to 2013 required revision (p <0.001). Nationally patients
      with a 4.0 cm cuff underwent fewer revisions during the latter era (16.2% vs
      7.5%, p = 0.001). In local and national cohorts Kaplan-Meier analysis revealed
      improved survival of the 4.0 cm cuff after the introduction of the 3.5 cm cuff (p
      <0.05). CONCLUSIONS: The incidence of artificial urinary sphincter revision
      surgery in patients with a 4.0 cm cuff has decreased since the availability of
      the 3.5 cm cuff. This suggests that precise cuff sizing appears to be beneficial
      in men with spongiosal atrophy.

PMID- 24746881
TI  - Inhibition of peripheral FAAH depresses activities of bladder mechanosensitive
      nerve fibers of the rat.
AB  - PURPOSE: FAAH degrades endocannabinoids and fatty acid amides. FAAH inhibition
      reduces micturition frequency and counteracts bladder overactivity in rats. We
      studied the effects of the peripherally active selective FAAH inhibitor URB937,
      and the CB1 and CB2 receptor antagonists rimonabant and SR144528, respectively,
      on single unit afferent activity of primary bladder afferents in rats. MATERIALS
      AND METHODS: Female Sprague Dawley(r) rats were anesthetized. Single unit
      afferent activity of Adelta or C-fibers from the L6 dorsal roots was recorded
      during bladder filling before and after URB937 administration with or without
      rimonabant or SR144528. Drugs (1 mg/kg) were given intravenously. FAAH, CB1 and
      CB2 expression, and expression of the sensory marker CGRP in the L6 dorsal root
      ganglion were compared by immunofluorescence. RESULTS: A total of 102 single
      afferent fibers (48 Adelta and 54 C-fibers) were isolated from 57 rats. URB937
      decreased single unit afferent activity of C-fibers to a mean +/- SEM of 78% +/-
      9% and of Adelta-fibers to a mean of 67% +/- 7% while increasing bladder
      compliance to a mean of 116% +/- 3%. The effects of URB937 on single unit
      afferent activity and bladder compliance were counteracted by rimonabant or
      SR144528. Rimonabant increased single unit afferent activity of each fiber type
      but SR144528 affected only Adelta-fiber activity. CGRP positive L6 dorsal root
      ganglion neurons showed strong FAAH, CB1 and CB2 staining. CONCLUSIONS: To our
      knowledge we report for the first time that inhibiting peripheral FAAH depresses
      the Adelta and C-fiber activity of primary bladder afferents via CB1 and CB2
      receptors. CB antagonists alone exerted facilitatory effects on single unit
      afferent activity during bladder filling in rats. The endocannabinoid system may
      be involved in physiological control of micturition as regulators of afferent
      signals.

PMID- 24746882
TI  - Does testosterone increase the risk of a cardiovascular event?

PMID- 24746884
TI  - The role of bedside ultrasound in pretherapeutic and posttherapeutic lumbar
      puncture in patient with idiopathic intracranial hypertension.
AB  - Idiopathic intracranial hypertension (IIH), also known as pseudotumor cerebri, is
      often a debilitating condition characterized by headaches, blurry vision, nausea,
      and vomiting. Lumbar puncture (LP) is an essential component of the diagnostic
      and therapeutic approach; however, the procedure itself can cause postlumbar
      puncture headache. In addition to the clinical presentation, the use of bedside
      ultrasound to measure the optic nerve sheath diameter may aid in differentiating
      the 2 conditions.We hereby report a case of a 33-year old woman with known IIH
      who presented with recurrent headache after the initial therapeutic LP.

PMID- 24746885
TI  - A novel multidimensional geriatric screening tool in the ED: evaluation of
      feasibility and clinical relevance.
AB  - PURPOSES: Geriatric problems frequently go undetected in older patients in
      emergency departments (EDs), thus increasing their risk of adverse outcomes. We
      evaluated a novel emergency geriatric screening (EGS) tool designed to detect
      geriatric problems. BASIC PROCEDURES: The EGS tool consisted of short validated
      instruments used to screen 4 domains (cognition, falls, mobility, and activities
      of daily living). Emergency geriatric screening was introduced for ED patients 75
      years or older throughout a 4-month period. We analyzed the prevalence of
      abnormal EGS and whether EGS increased the number of EGS-related diagnoses in the
      ED during the screening, as compared with a preceding control period. MAIN
      FINDINGS: Emergency geriatric screening was performed on 338 (42.5%) of 795
      patients presenting during screening. Emergency geriatric screening was
      unfeasible in 175 patients (22.0%) because of life-threatening conditions and was
      not performed in 282 (35.5%) for logistical reasons. Emergency geriatric
      screening took less than 5 minutes to perform in most (85.8%) cases. Among
      screened patients, 285 (84.3%) had at least 1 abnormal EGS finding. In 270 of
      these patients, at least 1 abnormal EGS finding did not result in a diagnosis in
      the ED and was reported for further workup to subsequent care. During screening,
      142 patients (42.0%) had at least 1 diagnosis listed within the 4 EGS domains,
      significantly more than the 29.3% in the control period (odds ratio 1.75; 95%
      confidence interval, 1.34-2.29; P<.001). Emergency geriatric screening predicted
      nursing home admission after the in-hospital stay (odds ratio for >=3 vs <3
      abnormal domains 12.13; 95% confidence interval, 2.79-52.72; P=.001). PRINCIPAL
      CONCLUSIONS: The novel EGS is feasible, identifies previously undetected
      geriatric problems, and predicts determinants of subsequent care.

PMID- 24746883
TI  - Heterogeneity in immune responses: from populations to single cells.
AB  - The mammalian immune system is tasked with protecting the host against a broad
      range of threats. Understanding how immune populations leverage cellular
      diversity to achieve this breadth and flexibility, particularly during dynamic
      processes such as differentiation and antigenic response, is a core challenge
      that is well suited for single cell analysis. Recent years have witnessed
      transformative and intersecting advances in nanofabrication and genomics that
      enable deep profiling of individual cells, affording exciting opportunities to
      study heterogeneity in the immune response at an unprecedented scope. In light of
      these advances, here we review recent work exploring how immune populations
      generate and leverage cellular heterogeneity at multiple molecular and phenotypic
      levels. Additionally, we highlight opportunities for single cell technologies to
      shed light on the causes and consequences of heterogeneity in the immune system. 

PMID- 24746886
TI  - Tumour associated epilepsy and glutamate excitotoxicity in patients with gliomas.
AB  - Tumour associated epilepsy (TAE) is common, debilitating and often not
      successfully controlled by surgical resection of the tumour and administration of
      multiple anti-epileptic drugs. It represents a cause of significant lost quality
      of life in an incurable disease and is therefore an important subject for ongoing
      research. The pathogenesis of TAE is likely to be multifactorial and involve, on
      the microscopic level, the interaction of genetic factors, changes in the
      peritumoural microenvironment, alterations in synaptic neurotransmitter release
      and re-uptake, and the excitotoxic effects of glutamate. On a macroscopic level,
      the occurrence of TAE is likely to be influenced by tumour size, location and
      interaction with environmental factors. The optimal treatment of TAE requires a
      multi-disciplinary approach with input from neurosurgeons, neurologists,
      radiologists, pathologists and basic scientists. This article reviews the current
      literature regarding the incidence, treatment, and aetiology of TAE. 

PMID- 24746888
TI  - Rapid production of HIV-1 neutralizing antibodies in baculovirus infected insect
      cells.
AB  - Broadly neutralizing antibodies have been shown promise as prophylactic and
      therapeutic agents to provide passive protection against human immunodeficiency
      virus type 1 (HIV-1) infection. Such protein based microbicides are traditionally
      produced using mammalian cell expression system, which is not able to satisfy the
      increasing demand of these proteins in large scale. In this report, two of HIV-1
      broadly neutralizing antibodies, b12 and VRC01, were successfully expressed in
      Sf9 insect cells by co-infection with baculoviruses respectively expressing the
      light and heavy chain of the antibodies. The purified antibodies are fully
      assembled as H2L2 (two heavy chains plus two light chains) heterodimer linked by
      covalent bonds. The b12 and VRC01 generated from insect cells reacted well to HIV
      1 gp120, and their antigen binding ability is comparable to the mammalian cell
      derived b12 as determined by ELISA and flow cytometry. Our data suggest that
      baculovirus/insect cell expression system can be utilized as an alternative to
      the mammalian expression system for the rapid production of HIV-1 broadly
      neutralizing antibodies. 

PMID- 24746887
TI  - Breast screening using 2D-mammography or integrating digital breast tomosynthesis
      (3D-mammography) for single-reading or double-reading--evidence to guide future
      screening strategies.
AB  - PURPOSE: We compared detection measures for breast screening strategies
      comprising single-reading or double-reading using standard 2D-mammography or
      2D/3D-mammography, based on the 'screening with tomosynthesis or standard
      mammography' (STORM) trial. METHODS: STORM prospectively examined screen-reading
      in two sequential phases, 2D-mammography alone and integrated 2D/3D-mammography,
      in asymptomatic women participating in Trento and Verona (Northern Italy)
      population-based screening services. Outcomes were ascertained from assessment
      and/or excision histology or follow-up. For each screen-reading strategy we
      calculated the number of detected and non-detected (including interval) cancers,
      cancer detection rates (CDRs), false positive recall (FPR) measures and
      incremental CDR relative to a comparator strategy. We estimated the false:true
      positive (FP:TP) ratio and sensitivity of each mammography screening strategy.
      Paired binary data were compared using McNemar's test. RESULTS: Amongst 7292
      screening participants, there were 65 (including six interval) breast cancers;
      estimated first-year interval cancer rate was 0.82/1000 screens (95% confidence
      interval (CI): 0.30-1.79/1000). For single-reading, 35 cancers were detected at
      both 2D and 2D/3D-mammography, 20 cancers were detected only with 2D/3D
      mammography compared with none at 2D-mammography alone (p<0.001) and 10 cancers
      were not detected. For double-reading, 39 cancers were detected at 2D-mammography
      and 2D/3D-mammography, 20 were detected only with 2D/3D-mammography compared with
      none detected at 2D-mammography alone (p<0.001) and six cancers were not
      detected. The incremental CDR attributable to 2D/3D-mammography (versus 2D
      mammography) of 2.7/1000 screens (95% CI: 1.6-4.2) was evident for single and for
      double-reading. Incremental CDR attributable to double-reading (versus single
      reading) of 0.55/1000 screens (95% CI: -0.02-1.4) was evident for 2D-mammography
      and for 2D/3D-mammography. Estimated FP:TP ratios showed that 2D/3D-mammography
      screening strategies had more favourable FP to TP trade-off and higher
      sensitivity, applying single-reading or double-reading, relative to 2D
      mammography screening. CONCLUSION: The evidence we report warrants rethinking of
      breast screening strategies and should be used to inform future evaluations of
      2D/3D-mammography that assess whether or not the estimated incremental detection
      translates into improved screening outcomes such as a reduction in interval
      cancer rates.

PMID- 24746889
TI  - Author's response to letter by Whitlow et al.

PMID- 24746890
TI  - Environmental externality and inequality in China: current status and future
      choices.
AB  - Along with China's rapid economic growth, the environmental externality in the
      country is getting more and more serious. China's environmental externality is
      accompanied by environmental inequality, which presents two characteristics:
      First, the health loss caused by environmental externality is concentrated in the
      elderly and children. We take Beijing as an empirical analysis to conclude that
      children (0-4 years old) are the largest group suffered from respiratory disease;
      while the seniors are the largest group suffered from cardiovascular disease.
      Second, China's environmental inequality is mainly caused by the transfer of
      industries from urban to rural areas/suburbs. The villagers in poor rural areas
      are the biggest victims. China's environmental inequality is reflected
      particularly by the phenomenon of "cancer villages" which has existed ever since
      the end of 1970s. Finally, policy recommendations are provided for reducing
      China's environmental externality and inequality. 

PMID- 24746891
TI  - Managing urban nutrient biogeochemistry for sustainable urbanization.
AB  - Urban ecosystems are unique in the sense that human activities are the major
      drivers of biogeochemical processes. Along with the demographic movement into
      cities, nutrients flow towards the urban zone (nutrient urbanization), causing
      the degradation of environmental quality and ecosystem health. In this paper, we
      summarize the characteristics of nutrient cycling within the urban ecosystem
      compared to natural ecosystems. The dynamic process of nutrient urbanization is
      then explored taking Xiamen city, China, as an example to examine the influence
      of rapid urbanization on food sourced nitrogen and phosphorus metabolism.
      Subsequently, the concept of a nutrient footprint and calculation method is
      introduced from a lifecycle perspective. Finally, we propose three system
      approaches to mend the broken biogeochemical cycling. Our study will contribute
      to a holistic solution which achieves synergies between environmental quality and
      food security, by integrating technologies for nutrient recovery and waste
      reduction. 

PMID- 24746893
TI  - Letter to the Editor on "Article title misstates the role of pavement sealers".

PMID- 24746894
TI  - A novel analytical strategy for patient-physician communication research: the one
      with-many design.
AB  - OBJECTIVE: We aimed to demonstrate how a novel analytic strategy - the one-with
      many (OWM) design - can provide unique information about patient-physician
      communication that cannot be obtained using traditional analytic strategies.
      METHODS: Using an OWM design we conducted a secondary analysis of behavioral
      (talk time) and self-reported (perceived teamness) data from a study of patient
      physician communication, and examined variance decompositions of these variables.
      RESULTS: Talk time was largely relational, suggesting that there is no behavioral
      consistency on the part of physicians across patients or behavioral similarity
      among patients who see the same physician. In contrast, there was significant
      actor variance in perceived teamness, suggesting that some physicians
      consistently reported higher teamness with their patients than others. However,
      those physicians' positive perceptions of the communication are not necessarily
      reciprocated by their patients. CONCLUSIONS: OWM design provides researchers with
      the opportunity to take full advantage of rich non-independent data and explore
      interesting communication patterns (e.g., behavioral continuity, similarity,
      reciprocity unique to specific dyads) that have been omitted in prior literature.
      PRACTICAL IMPLICATIONS: OWM can be used to determine the relative differences in
      how patients and physicians influence communication patterns and identify which
      aspects of physician-patient communication are relational and which are not.

PMID- 24746895
TI  - Trajectories of prosocial behavior from adolescence to early adulthood:
      associations with personality change.
AB  - The goal of this study was to identify heterogenic longitudinal patterns of
      change in prosocial behavior from adolescence to early adulthood and their
      association with change in Big Five Factor (BFF) personality traits from
      adolescence until early adulthood. Participants were 573 Italian adolescents aged
      approximately 13 at the first assessment and 21 at the last assessment. Using
      growth mixture modeling, low increasing (LI; 18%), medium quadratic (MQ; 26%),
      and high quadratic (HQ; 54%) trajectories of prosocial behavior were
      distinguished. Generally, the LI trajectory group predicted an increase in
      Conscientiousness over time, whereas the HQ trajectory group predicted greater
      change in Agreeableness and Openness. In addition, positive changes in
      Conscientiousness, Agreeableness, and Openness between ages 13 and 21 predicted a
      higher probability of belonging to the HQ prosocial group. Findings support a
      malleable perspective on personality and identify longterm positive pathways for
      youths' prosocial development. 

PMID- 24746896
TI  - Prevalence and impact of colony stimulating factor 3 receptor (CSF3R) mutations
      among Egyptian acute myeloid leukemia patients.
AB  - Granulocyte-colony stimulating factor receptor (G-CSFR) mutations have been
      implicated in the progression of severe congenital neutropenia (SCN) to leukemia.
      This study aimed to investigate the prevalence of colony stimulating factor 3
      receptor (CSF3R) mutations among Egyptian acute myeloid leukemia and their clinic
      pathological impact. The study was conducted on 179 adult patients (156 de novo
      AML and 23 secondary AML on top of SCN). CSF3R mutations were analyzed by
      sequencing of the PCR products. CSF3R mutations were detected in 2 cases out of
      156 de novo AML patients (1.2%) and eighteen cases out of 23 secondary AML
      patients (78.2%). It was noticed that most of the mutant cases are of younger
      age, have a high white blood cells count, high bone marrow blasts, bad
      performance status, and absence of extra medullary disease and with low rate
      induction remission. Also the overall survival of AML patient's secondary to
      CSF3R mutations was shorter as compared to those with wild type AML cases. In
      conclusion the frequency of CSF3R mutations is highly prevalent among AML
      patients secondary to SCN compared to de novo AML. 

PMID- 24746897
TI  - Genotypic analysis of Pseudomonas aeruginosa isolated from ocular infection.
AB  - Pseudomonas aeruginosa is the causative pathogen of keratitis, conjunctivitis,
      and dacryocystitis. However little is known about their clinical epidemiology in
      Japan. In this study we investigated the genotypic characterization and serotype
      of P. aeruginosa isolates from ocular infections. Thirty-four clinical P.
      aeruginosa isolates were characterized according to infection type, the type III
      secretion system (TTSS), serotype, and multilocus sequence typing (MLST). We
      divided the isolates into four clinical infection types as follows: Contact lens
      (CL)-related keratitis (CL-keratitis; 15 isolates), non CL-related keratitis (non
      CL-keratitis; 8 isolates), conjunctivitis (7 isolates), and dacryocystitis (4
      isolates). Regarding the TTSS classification and serotyping classification, no
      significant differences were found among the infection types. Two clusters (I,
      II) and three subclusters (A, B, C) were classified according to MLST. CL
      keratitis isolates with exoU positivity were clustered in II-B, and
      conjunctivitis was clustered in cluster I. Some linkage was found between the
      genetic background and CL-keratitis or conjunctivitis. 

PMID- 24746898
TI  - Markers of small airway involvement and asthma control in patients with moderate
      to-severe asthma.

PMID- 24746899
TI  - Anti-angiogenesis participates in antitumor effects of metronomic capecitabine on
      colon cancer.
AB  - Inhibitory effects and potential mechanisms of capecitabine metronomic
      chemotherapy on colon cancer were investigated in this study. Metronomic
      chemotherapy with fluorouracil or capecitabine inhibited proliferation of colon
      cancer cells both in vitro and in vivo. Capecitabine metronomic chemotherapy
      demonstrated equal effects as CTX metronomic chemotherapy. Metronomic
      capecitabine or CTX chemotherapy decreased vascular endothelial growth factor
      (VEGF) but elevated thrombospondin-1 (TSP-1) expression, reduced CEP levels and
      decreased microvessel density (MVD). These results indicated anti-angiogenesis
      may be correlated with the antitumor effects of metronomic capecitabine in colon
      cancer.

PMID- 24746900
TI  - [A bone scintigraphy with abdominopelvic uptake of 99mTc-diphosphonate].

PMID- 24746901
TI  - Behavioral effects of perinatal opioid exposure.
AB  - Opioids are among the world's oldest known drugs used mostly for pain relief, but
      recreational use is also widespread. A particularly important problem is opioid
      exposure in females, as their offspring can also be affected. Adverse
      intrauterine and postnatal environments can affect offspring development and may
      lead to various disabilities later in life. It is clear that repetitive painful
      experiences, such as randomly occurring invasive procedures during neonatal
      intensive care, can permanently alter neuronal and synaptic organization and
      therefore later behavior. At the same time, analgesic drugs can also be harmful,
      inducing neuronal apoptosis or withdrawal symptoms in the neonate and behavioral
      alterations in adulthood. Hence, risk-benefit ratios should be taken into
      consideration when pain relief is required during pregnancy or in neonates.
      Recreational use of opioids can also alter many aspects of life. Intrauterine
      opioid exposure has many toxic effects, inducing poor pregnancy outcomes due to
      underdevelopment, but it is believed that later negative consequences are more
      related to environmental factors such as a chaotic lifestyle and inadequate
      prenatal care. One of the crucial components is maternal care, which changes
      profoundly in addicted mothers. In substance-dependent mothers, pre- and
      postnatal care has special importance, and controlled treatment with a synthetic
      opioid (e.g., methadone) could be beneficial. We aimed to summarize and compare
      human and rodent data, as it is important to close the gap between scientific
      knowledge and societal policies. Special emphasis is given to gender differences
      in the sensitivity of offspring to perinatal opioid exposure. 

PMID- 24746902
TI  - Phosphodiesterase 9: insights from protein structure and role in therapeutics.
AB  - This review focuses on the development of drugs targeting phosphodiesterase 9A
      (PDE9A). PDE9A normally regulates cGMP (cyclic guanosine monophosphate) levels,
      which in turn regulate signal transduction. However, in pathological conditions,
      PDE9A inhibition is required to treat diseases that lower the level of cGMP.
      Hence, there is a need for specific PDE9A inhibitors. Aligning the 3D structure
      of PDE9A with other phosphodiesterases reveals residues crucial to inhibitor
      selectivity. GLU406 is unique to PDE9A and stabilizes the side chain of an
      invariant glutamine (GLN453). TYR424 is another relevant residue, unique only to
      PDE9A and PDE8A. Therefore, TYR424 could discriminate between PDE9A and all other
      PDEs except PDE8A. TYR424 should also be considered in the design of selective
      inhibitors because PDE8A has low expression levels in the brain. Hence, GLU406
      and TYR424 are important target residues in the design of PDE9A-selective
      inhibitors. 

PMID- 24746903
TI  - An evaluation of an interprofessional master's level programme in children's
      palliative care: The students' evaluation.
AB  - In 2010/12 an innovative children's palliative care interprofessional educational
      project funded by the Irish Hospice Foundation was undertaken in a University
      faculty (Trinity College Dublin). This initiative responded to international
      educational recommendations to meet the palliative care needs of children. The
      project involved the development and delivery of 3 standalone modules at Master's
      level and a substantive research evaluation of the project to examine
      stakeholders and students perspectives to provide an insight into their
      experiences and to gather data for future developments. The research evaluation
      was conducted in two parts, part one sought students' evaluation and part two
      sought stakeholders', curriculum developers and lecturers' feedback. This paper
      reports the students' evaluation. Findings indicate that students perceived
      undertaking the modules provided them with the opportunity for improved
      interprofessional learning and they found modular content and assessment
      challenging. They also found the modules met their educational needs and also
      promoted an awareness of interprofessional education and the collaborative
      teamwork involved in children's palliative care. These students already
      experienced in children's palliative care indicated that those teaching on
      programmes at this level need expertise and programme time needs to be available
      for sharing experiences and for consolidation of learning. 

PMID- 24746904
TI  - [Non-alcoholic fatty liver: position document of the Catalan Society of
      Gastroenterology].

PMID- 24746905
TI  - [Colonic stromal pseudolipomatosis. An unexpected finding of histopathological
      analysis].

PMID- 24746906
TI  - Retroperitoneal and cutaneous necrotizing fasciitis secondary to necrotizing
      pancreatitis.
AB  - BACKGROUND: Retroperitoneal abscesses are rare complications of intraabdominal
      infectious processes and can progress to necrotizing infections. Necrotizing
      pancreatitis occurs in 10-25% of patients that require hospital admission for
      pancreatitis, is associated also with a 25% mortality rate, and may lead to
      formation of a retroperitoneal abscess. CASE REPORT: We report a case of a 63
      year-old woman with a recently resolved case of pancreatitis who presented to the
      Emergency Department (ED) with a painful nodule on her left flank for 3 weeks,
      rapidly progressing over the last 12 h. In the ED, examination revealed an
      expanding area of erythema over the left flank with sepsis. Computed tomography
      scan revealed necrotizing pancreatitis with retroperitoneal abscess tracking to
      the abdominal wall, resulting in necrotizing fasciitis. She was taken emergently
      to the operating room with a good outcome. WHY SHOULD AN EMERGENCY PHYSICIAN BE
      AWARE OF THIS?: Acute pancreatitis is common, with a minority of cases resulting
      in parenchymal necrosis, which can lead to retroperitoneal infections. Rarely,
      necrotizing fasciitis can present on the abdominal wall as a complication of
      intraabdominal or retroperitoneal infections. The emergency provider should be
      aware of these complications that may lead to necrotizing infections and a
      potentially indolent course.

PMID- 24746907
TI  - Toxicity of antihypertensives in unintentional poisoning of young children.
AB  - BACKGROUND: Knowledge is limited about the toxicity of unintentional exposure to
      antihypertensives in young children (0-6 years of age). OBJECTIVE: Our aim was to
      research symptoms and poisoning severity in unintentional poisonings in this
      group of age and determine adequate poisoning management. METHODS: We performed a
      10-year retrospective, explorative analysis of the Mainz Poison Center/Germany
      database with regard to circumstances of poison exposure, dosage, symptoms, and
      treatment. To be able to relate drug exposure with reported symptoms, analyses
      were restricted to single drug exposures. Written follow-up information was
      obtained in about 50% of all cases. RESULTS: A total of 1489 cases were analyzed,
      of which 957 were single drug exposures with 421 exposures to beta-blocking
      agents, 364 to inhibitors of the renin-angiotensin system, 122 to calcium channel
      blockers, and 50 to antiadrenergic drugs. No severe (Poisoning Severity Score
      [PSS]=3) or fatal poisonings (PSS=4) were reported and, with the exception of
      atenolol, propranolol, irbesartan, isradipin, clonidine, and moxonidine, no
      poisonings with a PSS>1. We did not find a significant relationship between
      dosage, release formulation and symptoms, or PSS. All patients fully recovered
      without specific treatment. CONCLUSIONS: In young children with unintentional,
      single drug exposure to the most popular antihypertensive medication (i.e.,
      metoprolol, bisoprolol, ramipril, enalapril, lisinopril, captopril, candesartan,
      valsartan, amlodipine, and verapamil), only mild symptoms occurred, and hospital
      evaluation is not a must. However, children with recent exposure to clonidine or
      moxonidine should be evaluated at a hospital due to an increased likelihood of
      poisonings of at least moderate severity.

PMID- 24746908
TI  - Bedside ultrasound diagnosis of an aortocaval fistula in the emergency
      department.

PMID- 24746909
TI  - Impact of mode of transportation on time to treatment in patients transferred for
      primary percutaneous coronary intervention.
AB  - BACKGROUND: Patients suffering ST segment elevation myocardial infarction (STEMI)
      requiring transfer from a non-percutaneous coronary intervention (PCI) hospital
      to a PCI-capable hospital often have prolonged treatment times. OBJECTIVE: For
      STEMI transfers, we changed from air to ground transportation, and carefully
      documented the impact on treatment times. METHODS: This is a retrospective report
      between two hospitals within one STEMI system. The referring facility controls
      both air and ground ambulance services. After a 2-year period of air
      transportation with suboptimal treatment times, the referring hospital switched
      to ground transport. All pertinent times were carefully recorded and are reported
      here. RESULTS: There were 43 patients included, approximately half were
      transported by air and half by ground. Comparing our early experience (air only)
      vs. our later experience (predominantly ground-transported patients), median door
      in-door-out (DIDO) time at the first facility was 70 min vs. 35 min (p<0.001),
      median transport time was 20 min vs. 30 min (p<0.001), and median first medical
      contact to balloon time (FMC2b time) was 123 min vs. 90 min (p<0.001). After
      changing mode of transport, achievement of the national FMC2b time goal of <120
      min rose from 47% to 92% (p<0.001). CONCLUSIONS: We document a significantly
      reduced DIDO and FMC2b time after changing mode of transportation for STEMI
      patients transferred 30 miles for primary PCI. Utilizing ground rather than air
      transportation, the median FMC2b time was reduced from 123 to 90 min. We show
      that mode of transportation can dramatically reduce both DIDO time and FMC2b
      time.

PMID- 24746910
TI  - Diagnosis of patellar tendon rupture by emergency ultrasound.

PMID- 24746911
TI  - Perilunate fracture dislocation.

PMID- 24746912
TI  - Stretching desmin filaments with receding meniscus reveals large axial tensile
      strength.
AB  - Desmin forms the intermediate filament system of muscle cells where it plays
      important role in maintaining mechanical integrity and elasticity. Although the
      importance of intermediate-filament elasticity in cellular mechanics is being
      increasingly recognized, the molecular basis of desmin's elasticity is not fully
      understood. We explored desmin elasticity by molecular combing with forces
      calculated to be as large as 4nN. Average filament contour length increased 1.55
      fold axial on average. Molecular combing together with EGTA-treatment caused the
      fragmentation of the filament into short, 60 to 120-nm-long and 4-nm-wide
      structures. The fragments display a surface periodicity of 38nm, suggesting that
      they are composed of laterally attached desmin dimers. The axis of the fragments
      may deviate significantly from that of the overstretched filament, indicating
      that they have a large orientational freedom in spite of being axially
      interconnected. The emergence of protofibril fragments thus suggests that the
      interconnecting head or tail domains of coiled-coil desmin dimers are load
      bearing elements during axial stretch. 

PMID- 24746913
TI  - Structural insights into regulatory mechanisms of MO25-mediated kinase
      activation.
AB  - The tumor suppressor kinase LKB1 and germinal center kinases (GCKs) are key
      regulators of various cellular functions. The adaptor molecule MO25 not only
      recruits and activates LKB1 through the pseudokinase STRAD, but also may directly
      activate GCKs like MST3, MST4, STK25, OSR1 and SPAK. Targeting MO25 in a
      pathological setting has been recently studied in mouse. Yet the regulatory
      mechanism of MO25-mediated kinase activation is not fully understood. Here, our
      structural studies of MO25-related kinases reveal that MO25 binds to and
      activates GCK kinases or pseudokinase through a unified structural mechanism,
      featuring an active conformation of the alphaC helix and A-loop stabilized by
      MO25. Compared to GCKs that are directly activated by MO25-binding, activation of
      LKB1 has evolved additional layer of regulatory machinery, i.e., MO25 "activates"
      the pseudokinase STRAD, which in turn activates LKB1. Importantly, the structures
      of MO25alpha-STK25 and MO25alpha-MST3 determined in this work represent a
      transition/intermediate state and a fully activated state, respectively during
      the MO25-mediated kinase activating process. 

PMID- 24746914
TI  - Recommendations for the use of methotrexate in rheumatoid arthritis: up and down
      scaling of the dose and administration routes.
AB  - OBJECTIVES: To describe the optimal therapeutic strategy for use of methotrexate
      in RA patients over the initial dose, route of administration, dose increase and
      decrease, patient monitoring, and use of folic/folinic acid. MATERIAL AND METHOD:
      Eleven clinical experts proposed some questions to be solved. A systematic
      literature search was conducted. The contents were selected in a work session and
      subsequently validated via email to establish the level of agreement. RESULTS:
      The initial dose of methotrexate should not be <10mg/week, preferably orally, but
      considering the parenteral route as an alternative due to compliance, non
      effectiveness of treatment or gastrointestinal side effects, polypharmacy,
      obesity (if required doses are >20mg/week), patient preference, very active
      disease or to avoid administration errors. Changing to a parenteral
      administration is proposed when the oral route is not effective enough,
      gastrointestinal toxicity appears, there is non-compliance or due to cost
      effectiveness reasons before using more expensive drugs. On the contrary, due to
      patient preferences, intolerance to injections, dose reduction <7.5mg/week, non
      effectiveness of the route, poor compliance or gastrointestinal side effects.
      There should be a rapid dose escalation if inadequate responses occurr up to 15
      20 or even 25mg/week in about 8 weeks, with increments of 2.5-5mg. The reduction
      will be carried out according to the dose the patient had, with decreases of 2.5
      5mg every 3-6 months. Patient monitoring should be performed every 1-1.5 months
      until stability and then every 1-3 months. CONCLUSIONS: This document pretends to
      solve some common clinical questions and facilitate decision-making in RA
      patients treated with methotrexate.

PMID- 24746915
TI  - Cryptococcal meningoencephalitis in a patient with rheumatoid arthritis treated
      with methotrexate and prednisone.

PMID- 24746916
TI  - Efficacy of passive extension mobilization in addition to exercise in the
      osteoarthritic knee: an observational parallel-group study.
AB  - STUDY DESIGN: Pretest post-test observational parallel-group design. OBJECTIVES:
      To evaluate the efficacy of passive knee extension mobilization in addition to
      exercise therapy on extension range of motion (ROM) in patients with
      osteoarthritis (OA) of the knee. Secondary objectives were to determine changes
      in pain and functional abilities. BACKGROUND: Patients with knee OA complain of
      pain, limited range of motion, and impaired activities. Efficacy of mobilization
      as a treatment option next to exercises has not been studied rigorously. METHODS
      AND MEASURES: Thirty-four participants with persistent knee pain, a positive
      radiography for knee OA, and a passive extension deficit were included. Seventeen
      participants (mean age+/-SD, 59.8+/-6.1years) were treated with an exercise
      protocol and were additionally given manual mobilizations to improve passive
      extension ROM. The other group (mean age+/-SD, 61.5+/-7.3years) with equal
      characteristics was treated with an identical exercise therapy protocol only.
      Prior to participation, detailed ROM measurements were recorded next to muscle
      function tests, pain (VAS), six-minute walking tests (6MWTs), a condition
      specific questionnaire, and the patient-specific function scale (PSFS).
      Participants in both groups completed 16 treatment sessions each. RESULTS:
      Passive mobilization significantly improved extension ROM in the intervention
      group (5.2 versus 8.6 degrees , p=.017). The manually mobilized group also had
      better physical capacities as assessed by 6MWT, less pain, and a lower PSFS
      score. CONCLUSION: A combined protocol including exercise therapy and passive
      mobilization was beneficial for patients with OA of the knee complaining of pain,
      decreased extension ROM and decreased limited abilities. LEVEL OF EVIDENCE:
      Therapy, 2b.

PMID- 24746917
TI  - Obesity and pancreatic cancer.
AB  - BACKGROUND: Pancreatic cancer is an invariably fatal malignancy. Cigarette
      smoking and diabetes are established risk factors, but over the last two decades
      studies have shown that excess adiposity is an additional independent risk factor
      with 30-50% of cases thought to be attributed to nutritional factors. The aim of
      this narrative review is to analyze all the epidemiological evidence on the topic
      and possible pathophysiology. METHODS: We searched PubMed, Embase, Cochrane
      Library and Medline, and all available evidence was included. We firstly analyze
      meta- and pooled analysis. Then we discuss individual studies to identify sources
      of discrepancies between studies and attempt to delineate pathophysiology.
      RESULTS: It is estimated that obese individuals have a relative risk (RR) ranging
      between 1.19 and 1.47, when compared with those of normal weight, regardless of
      diabetes or smoking status. No significant differences were found between gender.
      CONCLUSION: There is a measurable increased risk of developing pancreatic cancer
      in obese individuals, and excess adiposity is related to the condition with a
      "dose-response" curve. Hyperinsulinemia and possibly hyperestrogenism secondary
      to a metabolic syndrome, and independently from diabetes status, appear to be the
      key elements of the pathogenesis in pancreatic cancer secondary to excess body
      fat. Increased efforts should therefore be made in tackling the epidemic levels
      of obesity in the Western world countries.

PMID- 24746918
TI  - Does transpalatal distraction affect pharyngeal airway dimensions and related
      soft tissues?
AB  - PURPOSE: Previous studies of transpalatal distraction (TPD) have been based on
      dentoskeletal alterations of the jaws and nasal airway changes. The main aim of
      this study was to determine the effects of TPD on soft palate and pharyngeal
      airway dimensions and tongue posture. MATERIAL AND METHODS: This was a
      retrospective cohort study. The sample was comprised of 16 patients with skeletal
      maxillary deficiency who had bilateral crossbite combined with a high palatal
      vault and partial or near total nasal obstruction treated with TPD using bone
      borne distractors (Transpalatal Distractor, SurgiTec NV, Bruges, Belgium). This
      research was carried out on lateral cephalometric radiographs taken before
      distraction and after a distraction period of 6.75 +/- 1.61 months. The primary
      predictor variable was pharyngeal airway dimensions and tongue posture. Other
      variables were demographic and lateral cephalometric parameters. Changes in the
      length, angle, and thickness of the soft palate; nasopharyngeal, retropalatal,
      retroglossal, and lower pharyngeal airway dimensions; and tongue length and
      height were evaluated. Data were analyzed by paired t test. RESULTS: The sample
      included 16 adult patients (mean age, 25.13 +/- 6.13 yr; 7 women, 9 men). The
      desired amount of distraction was achieved in all patients within 7 to 10 days.
      The total activation average was 8.38 +/- 0.96. TPD caused statistically
      significant changes in sagittal nasopharyngeal airway dimensions (1.19 mm), the
      minimal oropharyngeal distance behind the tongue base (1.81 mm), and tongue
      height (2.12 mm). CONCLUSIONS: The results of this study suggest that, in adult
      patients with nasal obstruction, TPD has the potential to increase sagittal
      nasopharyngeal airway dimensions and the minimal oropharyngeal distance behind
      the tongue, with an elevation in tongue posture. Further studies using cone-beam
      computed tomography that focus on how the bone-borne expander alters pharyngeal
      airway volume will make valuable contributions to the literature.

PMID- 24746919
TI  - Dysmenorrhea, absenteeism from school, and symptoms suspicious for endometriosis
      in adolescents.
AB  - STUDY OBJECTIVE: To quantify in adolescents the prevalence of dysmenorrhea and
      other symptoms found to be suggestive of future diagnosis of endometriosis, in
      particular their impact on monthly absenteeism from school/work, activity
      impairment, and sexual life and to quantify the awareness of endometriosis in
      adolescents. DESIGN: Cross-sectional study. SETTING: Academic institution.
      PATIENTS: Adolescents (n = 250) aged 14-20 years referring to 3 family Counseling
      services. INTERVENTIONS: Participants completed an anonymous questionnaire. MAIN
      OUTCOME MEASURES: Prevalence of dysmenorrhea and absenteeism from school/work
      during menses. Other outcomes were impairment of daily activities, dyspareunia,
      and awareness of endometriosis as a pathologic condition. RESULTS: 68% (170/250)
      of the participants complain of dysmenorrhea, 12% (30/250) lose days of
      school/work monthly because of dysmenorrhea, 13% (33/250) complain of
      intermenstrual pain which limits daily activities, 27% (56/208) of the
      adolescents who are sexually active complain of dyspareunia, 82% (203/250) have
      never heard about endometriosis and 80% (200/250) would like to know more about
      it. A significant association was found between severe dysmenorrhea, absenteeism
      from school/work, and basic level of education. Absence from school/work during
      menses showed an adjusted odds ratio for severe dysmenorrhea about 28 times
      greater than those who did not declare absenteeism (95%CI 7.898-98.920, P<.000).
      CONCLUSIONS: The rates of dysmenorrhea and school absenteeism caused by
      dysmenorrhea are high. According to recent studies these patients are at higher
      risk of further development of endometriosis, whereas the knowledge of the
      disease is low among the adolescents investigated, so those involved with
      adolescents both in the health profession and particularly in schools and Family
      Counseling Services should be educated about endometriosis and its symptoms to
      reduce the significant lag time between symptoms and diagnosis.

PMID- 24746920
TI  - Development of a Spanish language fertility educational brochure for pediatric
      oncology families.
AB  - STUDY OBJECTIVE: Education materials detailing fertility preservation options
      geared towards pediatric oncology patients are inadequately available,
      particularly materials that are culturally tailored. An English language
      pediatric fertility preservation brochure was developed in 2011, and given the
      significance of family building among Hispanics, it is important to transcreate
      materials for these audiences using learner verification to explore the unique
      preferences of the population. DESIGN: Qualitative face-to-face interviews and
      focus groups. PARTICIPANTS: Spanish-speaking patients (n = 10), parents (n = 10),
      and healthcare providers (n = 5). Suggestions for revisions were tested with
      focus groups of the same population (N = 16). MAIN OUTCOME MEASURES: Design,
      readability, likelihood to read, and overall opinion. RESULTS: Feedback was
      organized into 2 distinct themes: design and reader action. Overall the majority
      of parents and patients wanted personal accounts of other patients who had
      undergone fertility preservation, as well as photos of actual patients. The
      medical terminology in the brochure was acceptable and understood by most. The
      majority of participants who preferred the design with vivid colors and patterns
      explained this was because that brochure also contained more relevant
      information; however, both brochures had identical information. Many participants
      explained they would be receptive to receiving the brochure and the reproductive
      health information should be reinforced throughout cancer care. CONCLUSIONS: A
      learner verification approach to create pediatric educational materials can
      judiciously identify unique preferences for information. These results will be
      utilized to educate Spanish-speaking pediatric oncology patients and their
      parents to improve decision-making processes regarding future parenthood.

PMID- 24746921
TI  - Structure and function of the ARH family of ADP-ribosyl-acceptor hydrolases.
AB  - ADP-ribosylation is a post-translational protein modification, in which ADP
      ribose is transferred from nicotinamide adenine dinucleotide (NAD(+)) to specific
      acceptors, thereby altering their activities. The ADP-ribose transfer reactions
      are divided into mono- and poly-(ADP-ribosyl)ation. Cellular ADP-ribosylation
      levels are tightly regulated by enzymes that transfer ADP-ribose to acceptor
      proteins (e.g., ADP-ribosyltransferases, poly-(ADP-ribose) polymerases (PARP))
      and those that cleave the linkage between ADP-ribose and acceptor (e.g., ADP
      ribosyl-acceptor hydrolases (ARH), poly-(ADP-ribose) glycohydrolases (PARG)),
      thereby constituting an ADP-ribosylation cycle. This review summarizes current
      findings related to the ARH family of proteins. This family comprises three
      members (ARH1-3) with similar size (39kDa) and amino acid sequence. ARH1
      catalyzes the hydrolysis of the N-glycosidic bond of mono-(ADP-ribosyl)ated
      arginine. ARH3 hydrolyzes poly-(ADP-ribose) (PAR) and O-acetyl-ADP-ribose. The
      different substrate specificities of ARH1 and ARH3 contribute to their unique
      roles in the cell. Based on a phenotype analysis of ARH1(-/-) and ARH3(-/-) mice,
      ARH1 is involved in the action by bacterial toxins as well as in tumorigenesis.
      ARH3 participates in the degradation of PAR that is synthesized by PARP1 in
      response to oxidative stress-induced DNA damage; this hydrolytic reaction
      suppresses PAR-mediated cell death, a pathway termed parthanatos. 

PMID- 24746922
TI  - ATP binding and hydrolysis by Saccharomyces cerevisiae Msh2-Msh3 are
      differentially modulated by mismatch and double-strand break repair DNA
      substrates.
AB  - In Saccharomyces cerevisiae, Msh2-Msh3-mediated mismatch repair (MMR) recognizes
      and targets insertion/deletion loops for repair. Msh2-Msh3 is also required for
      3' non-homologous tail removal (3'NHTR) in double-strand break repair. In both
      pathways, Msh2-Msh3 binds double-strand/single-strand junctions and initiates
      repair in an ATP-dependent manner. However, we recently demonstrated that the two
      pathways have distinct requirements with respect to Msh2-Msh3 activities. We
      identified a set of aromatic residues in the nucleotide binding pocket (FLY
      motif) of Msh3 that, when mutated, disrupted MMR, but left 3'NHTR largely intact.
      One of these mutations, msh3Y942A, was predicted to disrupt the nucleotide
      sandwich and allow altered positioning of ATP within the pocket. To develop a
      mechanistic understanding of the differential requirements for ATP binding and/or
      hydrolysis in the two pathways, we characterized Msh2-Msh3 and Msh2-msh3Y942A ATP
      binding and hydrolysis activities in the presence of MMR and 3'NHTR DNA
      substrates. We observed distinct, substrate-dependent ATP hydrolysis and
      nucleotide turnover by Msh2-Msh3, indicating that the MMR and 3'NHTR DNA
      substrates differentially modify the ATP binding/hydrolysis activities of Msh2
      Msh3. Msh2-msh3Y942A retained the ability to bind DNA and ATP but exhibited
      altered ATP hydrolysis and nucleotide turnover. We propose that both ATP and
      structure-specific repair substrates cooperate to direct Msh2-Msh3-mediated
      repair and suggest an explanation for the msh3Y942A separation-of-function
      phenotype.

PMID- 24746924
TI  - Error-free versus mutagenic processing of genomic uracil--relevance to cancer.
AB  - Genomic uracil is normally processed essentially error-free by base excision
      repair (BER), with mismatch repair (MMR) as an apparent backup for U:G
      mismatches. Nuclear uracil-DNA glycosylase UNG2 is the major enzyme initiating
      BER of uracil of U:A pairs as well as U:G mismatches. Deficiency in UNG2 results
      in several-fold increases in genomic uracil in mammalian cells. Thus, the
      alternative uracil-removing glycosylases, SMUG1, TDG and MBD4 cannot efficiently
      complement UNG2-deficiency. A major function of SMUG1 is probably to remove 5
      hydroxymethyluracil from DNA with general back-up for UNG2 as a minor function.
      TDG and MBD4 remove deamination products U or T mismatched to G in CpG/mCpG
      contexts, but may have equally or more important functions in development,
      epigenetics and gene regulation. Genomic uracil was previously thought to arise
      only from spontaneous cytosine deamination and incorporation of dUMP, generating
      U:G mismatches and U:A pairs, respectively. However, the identification of
      activation-induced cytidine deaminase (AID) and other APOBEC family members as
      DNA-cytosine deaminases has spurred renewed interest in the processing of genomic
      uracil. Importantly, AID triggers the adaptive immune response involving error
      prone processing of U:G mismatches, but also contributes to B-cell
      lymphomagenesis. Furthermore, mutational signatures in a substantial fraction of
      other human cancers are consistent with APOBEC-induced mutagenesis, with U:G
      mismatches as prime suspects. Mutations can be caused by replicative polymerases
      copying uracil in U:G mismatches, or by translesion polymerases that insert
      incorrect bases opposite abasic sites after uracil-removal. In addition,
      kataegis, localized hypermutations in one strand in the vicinity of genomic
      rearrangements, requires APOBEC protein, UNG2 and translesion polymerase REV1.
      What mechanisms govern error-free versus error prone processing of uracil in DNA
      remains unclear. In conclusion, genomic uracil is an essential intermediate in
      adaptive immunity and innate antiviral responses, but may also be a fundamental
      cause of a wide range of malignancies. 

PMID- 24746925
TI  - Spatial and temporal observation of phase-shift nano-emulsions assisted
      cavitation and ablation during focused ultrasound exposure.
AB  - BACKGROUND: Phase-shift nano-emulsions (PSNEs) with a small initial diameter in
      nanoscale have the potential to leak out of the blood vessels and to accumulate
      at the target point of tissue. At desired location, PSNEs can undergo acoustic
      droplet vaporization (ADV) process, change into gas bubbles and enhance focused
      ultrasound efficiency. The threshold of droplet vaporization and influence of
      acoustic parameters have always been research hotspots in order to spatially
      control the potential of bioeffects and optimize experimental conditions.
      However, when the pressure is much higher than PSNEs' vaporization threshold,
      there were little reports on their cavitation and thermal effects. OBJECT: In
      this study, PSNEs induced cavitation and ablation effects during pulsed high
      intensity focused ultrasound (HIFU) exposure were investigated, including the
      spatial and temporal information and the influence of acoustic parameters.
      METHODS: Two kinds of tissue-mimicking phantoms with uniform PSNEs were prepared
      because of their optical transparency. The Sonoluminescence (SL) method was
      employed to visualize the cavitation activities. And the ablation process was
      observed as the heat deposition could produce white lesion. RESULTS: Precisely
      controlled HIFU cavitation and ablation can be realized at a relatively low input
      power. But when the input power was high, PSNEs can accelerate cavitation and
      ablation in pre-focal region. The cavitation happened layer by layer advancing
      the transducer. While the lesion appeared to be separated into two parts, one in
      pre-focal region stemmed from one point and grew quickly, the other in focal
      region grew much more slowly. The influence of duty cycle has also been examined.
      Longer pulse off time would cause heat transfer to the surrounding media, and
      generate smaller lesion. On the other hand, this would give outer layer bubbles
      enough time to dissolve, and inner bubbles can undergo violent collapse and emit
      bright light.

PMID- 24746923
TI  - The contribution of co-transcriptional RNA:DNA hybrid structures to DNA damage
      and genome instability.
AB  - Accurate DNA replication and DNA repair are crucial for the maintenance of genome
      stability, and it is generally accepted that failure of these processes is a
      major source of DNA damage in cells. Intriguingly, recent evidence suggests that
      DNA damage is more likely to occur at genomic loci with high transcriptional
      activity. Furthermore, loss of certain RNA processing factors in eukaryotic cells
      is associated with increased formation of co-transcriptional RNA:DNA hybrid
      structures known as R-loops, resulting in double-strand breaks (DSBs) and DNA
      damage. However, the molecular mechanisms by which R-loop structures ultimately
      lead to DNA breaks and genome instability is not well understood. In this review,
      we summarize the current knowledge about the formation, recognition and
      processing of RNA:DNA hybrids, and discuss possible mechanisms by which these
      structures contribute to DNA damage and genome instability in the cell. 

PMID- 24746926
TI  - Relatives' perspectives on the quality of care in an Intensive Care Unit: the
      theoretical concept of a new tool.
AB  - OBJECTIVE: To examine the potential of a questionnaire (CQI 'R-ICU') to measure
      the quality of care from the perspective of relatives in the Intensive Care Unit
      (ICU). METHODS: A quantitative survey study has been undertaken to explore the
      psychometric properties of the instrument, which was sent to 282 relatives of ICU
      patients from the Erasmus MC, an academic hospital in Rotterdam, the Netherlands.
      Factor-analyses were performed to explore the underlying theoretical structure.
      RESULTS: Survey data from 211 relatives (response rate 78%) were used for the
      analysis. The overall reliability of the questionnaire was sufficiently high; two
      of the four underlying factors, namely 'Communication' and 'Involvement', were
      significant predictors. Two specific aspects of care that needed the most
      improvement were missing information about meals and offering an ICU diary. There
      is a significant difference in mean communication with nurses among the four
      wards in Erasmus MC. CONCLUSIONS: The CQI 'R-ICU' seems to be a valid, reliable
      and usable instrument. The theoretical fundament appears to be related to
      communication. PRACTICE IMPLICATIONS: The newly developed instrument can be used
      to provide feedback to health care professionals and policy makers in order to
      evaluate quality improvement projects with regard to relatives in the ICU.

PMID- 24746927
TI  - Biodiversity in intertidal rock pools: informing engineering criteria for
      artificial habitat enhancement in the built environment.
AB  - Coastal defence structures are proliferating to counter rising and stormier seas.
      With increasing concern about the ecological value of built environments, efforts
      are being made to create novel habitat to increase biodiversity. Rock pools are
      infrequent on artificial structures. We compared biodiversity patterns between
      rock pools and emergent rock and assessed the role of pool depth and substratum
      incline in determining patterns of biodiversity. Rock pools were more taxon rich
      than emergent substrata. Patterns varied with depth and incline with algal groups
      being more positively associated with shallow than deeper habitats. Substratum
      incline had little influence on colonising epibiota, with the exception of canopy
      algae in deeper habitats where vertical surfaces supported greater taxon richness
      than horizontal surfaces. The creation of artificial rock pools in built
      environments will have a positive effect on biodiversity. Building pools of
      varying depths and inclines and shore heights will provide a range of habitats,
      increase environmental heterogeneity, therefore creating more possible ecological
      niches, promoting local biodiversity.

PMID- 24746928
TI  - Are there any gender differences in the hippocampus volume after head-size
      correction? A volumetric and voxel-based morphometric study.
AB  - Previous findings on normal sexual dimorphism in hippocampal volume have not
      always been consistent. This study investigated gender differences in hippocampal
      volume using different head-size correction strategies. T1-weighted MR images
      were collected in 99 healthy, Caucasian, university students (66 female subjects;
      mean age: 23.1 +/- 2.3, range: 19-31 years). Sexual dimorphism in hippocampus was
      investigated by automated MRI volumetry and voxel-based morphometry (VBM) using
      both general linear model (GLM) and proportion head-size correction strategies.
      Absolute hippocampal volumes were larger in men than women. After adjusting for
      head-size, the proportion method indicated larger hippocampi in women than men,
      while no gender differences were found using the GLM approach. Investigating
      absolute hippocampal volumes in 15 head-size matched pairs of males and females
      indicated no gender differences. We suggest that there is no sexual dimorphism in
      hippocampal size and the apparent gender differences found by the proportion
      method may have more to do with head-size than with sex. The GLM and proportion
      head-size correction strategies are not interchangeable and may yield different
      results. The importance of the present findings is mostly related to scientific
      reproducibility across MRI volumetry or VBM studies.

PMID- 24746929
TI  - Association of APOE polymorphisms and stressful life events with dementia in a
      Pakistani population.
AB  - Dementia is a major public health problem worldwide. Alzheimer's disease (AD) is
      a major form of dementia and the APOE 4 allele is an established genetic risk
      factor for AD. Similarly, stressful life events are also associated with
      dementia. The objective of this study was to examine the association of APOE 4
      and stressful life events with dementia in a Pakistani sample, which to our
      knowledge has not been reported previously. We also tested for an interaction
      between stressful life events and APOE 4 on dementia risk. A total of 176
      subjects (61 cases and 115 controls) were recruited. All cases and healthy
      controls were interviewed to assess cognition, co-morbidities, history of
      stressful life events and demographics. Blood genotyping for the APOE
      polymorphism (E2/E3/E4) was performed. APOE 4 and stressful life events were each
      independently and significantly associated with the risk of dementia (APOE 4:
      P=0.00697; stressful life events: P=5.29E-09). However, we did not find a
      significant interaction between APOE 4 carrier status and stressful life events
      on risk of dementia (P=0.677). Although the sample size of this study was small,
      the established association of APOE 4 with dementia was confirmed the first time
      in a Pakistani sample. Furthermore, stressful life events were also found to be
      significantly associated with dementia in this population.

PMID- 24746930
TI  - Long-term pre-exposure of pheochromocytoma PC12 cells to endocrine-disrupting
      chemicals influences neuronal differentiation.
AB  - This study examined the effects of exposure to low concentrations (0.1-100 nM) of
      bisphenol A (BPA) or nonylphenol (NP) on neuronal differentiation in
      pheochromocytoma PC12 cells. Pre-exposure to BPA for a week or a month, but not
      for a day, decreased neuronal differentiation in PC12 cells. Likewise, one week's
      pre-exposure to NP also inhibited neuronal differentiation in these cells. The
      inhibitory effects were still observed when PC12 cells were treated with BPA or
      NP for a week, followed by a week's withdrawal. These findings suggest that long
      term exposure of PC12 cells to low concentrations of BPA or NP leads to changes
      in the cellular machinery responsible for neuronal differentiation, and these
      changes might be retained within PC12 cells.

PMID- 24746931
TI  - Cognitive improvement of mice induced by exercise prior to traumatic brain injury
      is associated with cytochrome c oxidase.
AB  - Though the evidence demonstrated that voluntary exercise programs could be
      implemented to enhance recovery of cognitive function induced by traumatic brain
      injury (TBI), the exact mechanisms were still not known. We proposed that the
      cognitive improvement induced by exercise in TBI mice is associated with
      cytochrome c oxidase (COX). To demonstrate this hypothesis, adult mice were
      housed with or without access to a running wheel (RW) for three weeks followed by
      TBI operation. Acquisition of spatial learning and memory retention was assessed
      by using the Morris Water Maze (MWM) on days 15 post TBI. The synaptic density
      was measured by Golji staining. Immunohistochemistry (IHC) for NeuN, GFAP and
      growth associated protein 43 (GAP43) were also performed. Using Western blot, the
      expressions of COX I, II, III, BDNF, synapsin I, synaptophysin (SYP) and GAP43 in
      hippocampus of TBI mice were determinated. Lastly, CcO activity and ATP amount
      were also detected. Results showed that voluntary exercise prior TBI: (i)
      counteracted the cognitive deficits and neuron and synaptic density loss
      associated with the injury; (ii) increased the levels of COX I, II, III, BDNF,
      synapsin I, SYP and GAP43; (iii) switched the mitochondrial CcO activity and ATP
      amounts. These studies demonstrated that the COX plays an important role in
      exercise's cognitive effects in TBI model and also provide evidence that RW
      training is a promise exercise for traumatically injured mice.

PMID- 24746932
TI  - Comparisons of cognitive function and serum S-100B level between diabetic and non
      diabetic patients after the implantation of carotid artery stent (CAS).
AB  - To investigate cognitive function improvement in diabetic and non-diabetic
      patients after the implantation of Carotid Artery Stent (CAS), 128 patients
      suffering severe carotid stenosis were successfully enrolled in this study. Tests
      including, the Mini Mental State Examination (MMSE), Montreal Cognitive
      Assessment (MoCA), Alzheimer's Disease Assessment Scale-Cognitive subscale (ADAS
      Cog), Clock Drawing Test (CDT), Hasegawa's Dementia Scale-Revised (HDS-R) and the
      serum levels of S-100B, were all measured at baseline for 3 months after the
      implantation of CAS. The baseline characteristics were similar between the
      patients with and without diabetes. 3 months after the implantation, significant
      improvements in MMSE (24.8 +/- 2.2 vs. 25.2 +/- 2.1, p=0.003), MoCA (25.6 +/- 2.0
      vs. 26.1 +/- 1.9, p=0.000), ADAS-Cog (6.5 +/- 1.3 vs. 6.1 +/- 1.3, p=0.000), and
      CDT (3.3 +/- 0.7 vs. 3.5 +/- 0.7, p=0.034) were observed in the non-diabetic
      group. In contrast, there was no significant improvement in any of the cognitive
      test for the diabetic group. Another interesting discovery was the CAS procedure
      significantly decreased the S-100B level in the non-diabetic group (0.11 +/- 0.04
      ng/mL vs. 0.10 +/- 0.04 ng/mL, p=0.000), but similar phenomena were not
      discovered in the diabetic group. In this light, the change of the S-100B level
      was negatively correlated with the results in the MMSE (p<0.01) and the MoCA
      (p<0.01) tests, and positively correlated with the result in ADAS-Cog (p<0.05)
      test. Our findings suggest that the CAS-induced beneficial effects on cognitive
      function might have a correlation relationship with the serum level of S-100B.

PMID- 24746933
TI  - Elevated levels of cerebrospinal fluid neuron-specific enolase (NSE) in
      Alzheimer's disease.
AB  - Neuron-specific enolase (NSE) is a neuronal glycolytic enzyme of which
      cerebrospinal fluid (CSF) levels are found altered following acute or prolonged
      neuronal damage. Investigations concerning the role of NSE in Alzheimer's disease
      (AD) are conflicting with both elevated and reduced levels. We measured CSF
      levels of NSE in 32 patients with AD and 32 healthy subjects (HS) using an
      electrochemiluminescence immunoassay (ECLIA). Mean levels of adjusted NSE were
      significantly elevated in AD (18.12 ng/mL (95% CI 15.63-20.60), HS 8.46 ng/mL
      (95% CI 5.98-10.94), p=0.00002) and effect size for mean group differences high
      (1.84). NSE alone (cut-off score 15.80 ng/mL, 94% sensitivity, 97% specificity)
      and in combination with T-tau and P-Tau had high diagnostic accuracy to
      differentiate AD from HS. NSE correlated significantly with T-tau (r >= 0.87,
      p<0.000001) and P-tau (r >= 0.88, p<0.000001) in both AD and HS. Our results
      indicate elevated CSF-NSE levels to reflect altered neuronal metabolism in AD
      that may be used in supporting AD diagnostics.

PMID- 24746934
TI  - Optimal timing of pulmonary metastasectomy--is a delayed operation beneficial or
      counterproductive?
AB  - INTRODUCTION: Pulmonary metastasectomy represents an established approach in the
      treatment of lung metastases related to several solid malignant tumors, promising
      the chance of long term survival. Regarding the proper timing of metastasectomy
      both operation promptly after diagnosis and delayed operation after an interval
      of 3 months are common practice. MATERIALS AND METHODS: A systematic Medline
      search addressing the optimal timing of metastasectomy was performed. Since the
      search query "timing of metastasectomy" yields only a limited number of articles,
      the Medline search was expanded to include the main arguments for prompt
      metastasectomy ("metastases of metastasis", "growth rate of pulmonary
      metastases") and for delayed metastasectomy. RESULTS: Based on the data available
      to date, there is no necessity to expedite the timing of the operation. On the
      other hand, there is no evidence that a delayed operation, for example after re
      staging following an interval of 3 months, provides a benefit. CONCLUSION:
      Therefore the timing of metastasectomy should only depend on the patient's
      requirements, such as general state of health and oncologic considerations, such
      as promising multimodal therapy concepts, extrathoracal tumor manifestations or
      oncologic type of the primary tumor. A delayed operation seems justified if the
      indication for resection is questionable due to a high risk of early multilocal
      recurrence.

PMID- 24746935
TI  - Impact of radical operative treatment on the quality of life in women with vulvar
      cancer--a retrospective study.
AB  - OBJECTIVES: For patients undergoing vulva surgery the quality of life (QoL) is
      generally accepted as an important outcome parameter in addition to long-term
      survival, mortality and complication rates. Less radical operative treatment can
      reduce morbidity and thereby improve quality of life. This study focuses on
      outcome in terms of QoL in patients comparing wide local excision (WLE) with
      radical vulvectomy and waiver of lymphonodectomy (LNE) with inguinofemoral
      lymphonodectomy. METHODS: In a retrospective single-center study from 2000 to
      2010, 199 patients underwent surgery for vulvar cancer. To assess QoL, the EORTC
      QLQ-C30 and a tumor-specific module questionnaire were sent to all patients in
      the follow-up period. RESULTS: Women who underwent WLE have a superior QoL with
      regard to global health status and physical, role, emotional and cognitive
      functioning than those who underwent radical vulvectomy. Less radical surgery
      also implies less fatigue, nausea/vomiting, pain, insomnia, appetite loss,
      diarrhea and financial difficulties. After radical vulvectomy 89% of patients
      have sexual complications. CONCLUSION: Radical operative treatment, such as
      radical vulvectomy, causes deterioration in the QoL of these patients. An
      individualized, less radical surgery must be the aim in the treatment of vulvar
      cancer.

PMID- 24746936
TI  - Host responses of Japanese flounder Paralichthys olivaceus with lymphocystis cell
      formation.
AB  - Lymphocystis disease virus (LCDV) is the causative agent of lymphocystis disease
      (LCD). In this study, we investigated the mechanisms of lymphocystis cell (LCC)
      formation from the viewpoint of gene expression changes in the infected fish. LCC
      occurrence and virus titers in the experimentally infected Japanese flounder,
      Paralichthys olivaceus were monitored by visual confirmation and real-time PCR,
      respectively. The gene expression changes in the fish fin were investigated by
      microarray experiments. LCCs firstly appeared in the fish at 21 days post
      infection (dpi). LCD incidence increased with time and reached 92.9% at 62 dpi.
      LCDV genome was firstly detected from dorsal fins at 14 dpi, and the relative
      amount of the genome gradually-increased until 56 dpi. Since the occurrence of
      LCC was approximately synchronized with increasing of the virus genome, virus
      replication might play important roles for LCC formation. The microarray detected
      a few gene expression changes until 28 dpi. However, the number of expression
      changed genes dramatically increased between 28 and 42 dpi in which LCCs
      formation was active. From the microarray data analyses, apoptosis and cell
      division related genes were down-regulated, whereas cell fusion and collagen
      related genes were up-regulated at 42 dpi. Together with the observation of
      morphological changes of LCCs in previous reports, it is suggested that the
      following steps are involved in LCC formation: the virus infected cells were (1)
      inhibited apoptotic death and (2) cell division before enlargement, (3)
      hypertrophied by cell fusion, and (4) surrounded by a hyaline capsule associated
      with the alteration of collagen fibers. 

PMID- 24746937
TI  - Cell-penetrating peptides mediated protein cross-membrane delivery and its use in
      bacterial vector vaccine.
AB  - It is an attractive strategy to develop a recombinant bacterial vector vaccine by
      expressing exogenous protective antigen to induce the immune response, and the
      main concern is how to enhance the cellular internalization of antigen produced
      by bacterial vector. Cell-penetrating peptides (CPPs) are short
      cationic/amphipathic peptides which facilitate cellular uptake of various
      molecular cargoes and therefore have great potentials in vector vaccine design.
      In this work, eleven different CPPs were fused to the C-terminus of EGFP
      respectively, and the resultant EGFP-CPP fusion proteins were expressed and
      purified to assay their cross-membrane transport in macrophage J774 A.1 cells.
      Among the tested CPPs, TAT showed an excellent capability to deliver the cargo
      protein EGFP into cytoplasm. In order to establish an efficient antigen delivery
      system in Escherichia coli, the EGFP-TAT synthesis circuit was combined with an
      in vivo inducible lysis circuit PviuA-E in E. coli to form an integrated antigen
      delivery system, the resultant E. coli was proved to be able to lyse upon the
      induction of a mimic in vivo signal and thus release intracellular EGFP-TAT
      intensively, which were assumed to undergo a more efficient intracellular
      delivery by CPP to evoke protective immune responses. Based on the established
      antigen delivery system, the protective antigen gene flgD from an invasive
      intracellular fish pathogen Edwardsiella tarda EIB202, was applied to establish
      an E. coli recombinant vector vaccine. This E. coli vector vaccine presented
      superior immune protection (RPS = 63%) under the challenge with E. tarda EIB202,
      suggesting that the novel antigen delivery system had great potential in
      bacterial vector vaccine applications.

PMID- 24746938
TI  - Mass spectrometry defines the C-terminal dimerization domain and enables modeling
      of the structure of full-length OmpA.
AB  - The transmembrane domain of the outer membrane protein A (OmpA) from Escherichia
      coli is an excellent model for structural and folding studies of beta-barrel
      membrane proteins. However, full-length OmpA resists crystallographic efforts,
      and the link between its function and tertiary structure remains controversial.
      Here we use site-directed mutagenesis and mass spectrometry of different
      constructs of OmpA, released in the gas phase from detergent micelles, to define
      the minimal region encompassing the C-terminal dimer interface. Combining
      knowledge of the location of the dimeric interface with molecular modeling and
      ion mobility data allows us to propose a low-resolution model for the full-length
      OmpA dimer. Our model of the dimer is in remarkable agreement with experimental
      ion mobility data, with none of the unfolding or collapse observed for full
      length monomeric OmpA, implying that dimer formation stabilizes the overall
      structure and prevents collapse of the flexible linker that connects the two
      domains. 

PMID- 24746939
TI  - Z-Score: Fenton 2013. Ten-year update.

PMID- 24746940
TI  - Growth retardation and metabolic programming: implications and consequences for
      adult health and disease risk.

PMID- 24746941
TI  - Hear it playing low and slow: how pitch level differentially influences time
      perception.
AB  - Variations in both pitch and time are important in conveying meaning through
      speech and music, however, research is scant on perceptual interactions between
      these two domains. Using an ordinal comparison procedure, we explored how
      different pitch levels of flanker tones influenced the perceived duration of
      empty interstimulus intervals (ISIs). Participants heard monotonic, isochronous
      tone sequences (ISIs of 300, 600, or 1200 ms) composed of either one or five
      standard ISIs flanked by 500 Hz tones, followed by a final interval (FI) flanked
      by tones of either the same (500 Hz), higher (625 Hz), or lower (400 Hz) pitch.
      The FI varied in duration around the standard ISI duration. Participants were
      asked to determine if the FI was longer or shorter in duration than the preceding
      intervals. We found that an increase in FI flanker tone pitch level led to the
      underestimation of FI durations while a decrease in FI flanker tone pitch led to
      the overestimation of FI durations. The magnitude of these pitch-level effects
      decreased as the duration of the standard interval was increased, suggesting that
      the effect was driven by differences in mode-switch latencies to start/stop
      timing. Temporal context (One vs. Five Standard ISIs) did not have a consistent
      effect on performance. We propose that the interaction between pitch and time may
      have important consequences in understanding the ways in which meaning and
      emotion are communicated.

PMID- 24746942
TI  - The systemic exposure to inhaled beclometasone/formoterol pMDI with valved
      holding chamber is independent of age and body size.
AB  - BACKGROUND: Asthma guidelines recommend prescription of inhaled corticosteroids
      at a reduced dosage in children compared to older patients in order to minimize
      the systemic exposure and risk of unwanted side effects. In children, pressurized
      metered dose inhalers (pMDI) are recommended in combination with a valved holding
      chamber (VHC) to overcome the problem of coordinating inhalation with actuation.
      However, the influence of age and body size on the systemic exposure of drugs to
      be administered via a pMDI with VHC is still not fully elucidated. Therefore, we
      aimed to compare the systemic exposure to the active ingredients of a fixed
      combination of beclometasone-dipropionate/formoterol-fumarate administered via
      pMDI with VHC in children, adolescents and adults. METHODS: The pharmacokinetics
      of formoterol and beclometasone-17-monopropionate (active metabolite of
      beclometasone-dipropionate) was evaluated over 8 h from three studies, each
      performed in a different age and body size group. Children (7-11 years, n = 20),
      adolescents (12-17 years, n = 29) and adults (>=18 years, n = 24) received a
      single dose of beclometasone/formoterol (children: 200 MUg/24 MUg, adolescents
      and adults: 400 MUg/24 MUg) via pMDI with AeroChamber PlusTM. RESULTS: The
      systemic exposure in children in comparison to adolescents was equivalent for
      formoterol while it was halved for beclometasone-17-monopropionate in accordance
      with the halved dose of beclometasone administered in children (90% CIs within
      0.8-1.25 for formoterol and 0.4-0.625 for beclometasone-17-monopropionate). The
      systemic exposure to beclometasone-17-monopropionate and formoterol was
      equivalent between adolescents and adults. CONCLUSIONS: The systemic exposure to
      the active ingredients of a fixed dose combination of beclometasone/formoterol
      administered via pMDI with AeroChamber PlusTM correlates with the nominal dose
      independently of patient age and body size. Thus, dose reduction in relation to
      age when using a pMDI with VHC may be unnecessary for reducing the systemic
      exposure in children.

PMID- 24746943
TI  - Promoting cultural understanding through pediatric clinical dyads: an education
      research project.
AB  - This project explored the experiences of six undergraduate nursing students,
      three American nursing students and three nursing students from the Sultan of
      Oman, who participated in a faculty initiated education research project as part
      of their pediatric clinical practicum. Students were placed in dyads, with one
      American-born student and one Omani student in each dyad. Omani students also
      were paired with American nurse preceptors. A transcript-based content analysis
      was used to analyze data generated from qualitative focus group student
      interviews and student journals. The analysis generated three themes that
      described how myths were dispelled, cultural barriers were broken down and
      knowledge gained from another cultural perspective. The nurse preceptors were
      surveyed at the conclusion of the program. The survey findings suggest that
      preceptors gained a different cultural perspective of nursing care and they were
      better informed of the Omani students' learning needs. There was, however, an
      additional investment of preceptor time in meeting the learning needs of
      international students. Additional faculty time was also required for preparation
      and time during clinical conferencing to address differences in nursing practice
      between U.S. and Oman while meeting course learning objectives. Overall, the
      educational program provided evidence of enhancing American and Omani student
      cultural competence and Omani student adaptation to the United States. Coupling a
      domestic student with an international student to form dyads from the beginning
      of international students' experience could be a significant enhancement to both
      groups of students' learning experience. 

PMID- 24746944
TI  - MTHFR polymorphisms C677T and A1298C and associations with IVF outcomes in
      Brazilian women.
AB  - The aim of this study was to investigate the association between MTHFR gene
      polymorphisms and IVF outcomes in Brazilian women undergoing assisted
      reproduction treatment. A prospective study was conducted in the Human
      Reproduction Department at the ABC University School of Medicine and the Ideia
      Fertility Institute between December 2010 and April 2012. The patient population
      was 82 women undergoing assisted reproduction cycles. The MTHFR polymorphisms
      C677T and A1298C were evaluated and compared with laboratory results and
      pregnancy rates. The C677T variant was associated with proportions of mature
      (P=0.006) and immature (P=0.003) oocytes whereas the A1298C variant was
      associated with number of oocytes retrieved (P=0.044). The polymorphisms, whether
      alone or in combination, were not associated with normal fertilization, good
      quality embryo or clinical pregnancy rates. This study suggests that the number
      and maturity of oocytes retrieved may be related to the MTHFR polymorphisms C677T
      and A1298C. It is believed that folate has a crucial function in human
      reproduction and that folate deficiency can compromise the function of the
      metabolic pathways it is involved in, leading to an accumulation of homocysteine.
      The gene MTHFR encodes the 5-MTHFR enzyme, which is involved in folate
      metabolism, and C677T/A1298C polymorphisms of this gene are related to decreased
      enzyme activity and consequent changes in homocysteine concentration. Folate
      deficiency and hyperhomocysteinaemia can also compromise fertility and lead to
      pregnancy complications by affecting the development of oocytes, preparation of
      endometrial receptivity, implantation of the embryo and pregnancy. In
      folliculogenesis, hyperhomocysteinaemia can activate apoptosis, leading to
      follicular atresia and affecting the maturity of oocytes and the quality of
      embryos cultured in vitro. This study was performed to investigate the
      association between MTHFR polymorphisms and IVF outcomes in women undergoing
      assisted reproduction treatment.

PMID- 24746945
TI  - Tako-Tsubo cardiomyopathy presenting with cardiogenic shock successfully treated
      with milrinone: a case report.
AB  - We report the case of a middle age patient presenting with Tako-Tsubo
      cardiomyopathy (TTC) complicated by cardiogenic shock that was successfully
      handled with milrinone. A 64-year old man presented with cardiogenic shock after
      benzodiazepine and alcohol intoxication. A slight elevation of troponin and
      typical left ventricular ballooning without coronary lesions suggested TTC.
      Within a few hours milrinone infusion normalized the cardiac index. TTC is
      responsible for severe transient left ventricular dysfunction occurring after
      physical or psychological stress. The major pathophysiological mechanism involved
      is disproportionate catecholamine secretion, which may stun the myocardium. We
      considered if treatment of this unique physiopathology with catecholamines could
      be dangerous in these patients and if alternative inotropes such as milrinone
      should be preferred. 

PMID- 24746947
TI  - Electrophysiological analysis of the affective congruence between pattern
      regularity and word valence.
AB  - Reflection symmetry is an important property of human designs and biological
      organisms, and it is often judged to be beautiful. Previous reaction-time based
      studies have shown a congruency effect, where reflection symmetry facilitates
      processing of positive words, and random patterns facilitate negative words. But
      what is the neural basis of affective responses to symmetry? In Experiment 1 we
      recorded ERPs from posterior electrode clusters while participants viewed
      reflection or random patterns with either a positive or negative word
      superimposed. In the Discriminate Regularity task, participants categorized the
      patterns (reflection or random). In the Discriminate Word task, they categorized
      the words as positive or negative. In Experiment 2, participants classified words
      and patterns on each trial. We found a difference between ERP waves from
      congruent (reflection with positive word, random with negative word) and
      incongruent trials (reflection with negative, random with positive). This
      congruency effect began around 200 ms, and persisted up to 1,000 ms post
      stimulus, and was only present in the Discriminate Word task. We suggest that
      when evaluating words, participants automatically evaluate the background pattern
      as well, and this alters early visual processing.

PMID- 24746946
TI  - Abnormal dynamics of activation of object use information in apraxia: evidence
      from eyetracking.
AB  - Action representations associated with object use may be incidentally activated
      during visual object processing, and the time course of such activations may be
      influenced by lexical-semantic context (e.g., Lee, Middleton, Mirman, Kalenine, &
      Buxbaum (2012). Journal of Experimental Psychology: Human Perception and
      Performance, 39(1), 257-270). In this study we used the "visual world" eye
      tracking paradigm to examine whether a deficit in producing skilled object-use
      actions (apraxia) is associated with abnormalities in incidental activation of
      action information, and assessed the neuroanatomical substrates of any such
      deficits. Twenty left hemisphere stroke patients, ten of whom were apraxic,
      performed a task requiring identification of a named object in a visual display
      containing manipulation-related and unrelated distractor objects. Manipulation
      relationships among objects were not relevant to the identification task. Objects
      were cued with neutral ("S/he saw the...."), or action-relevant ("S/he used
      the....") sentences. Non-apraxic participants looked at use-related non-target
      objects significantly more than at unrelated non-target objects when cued both by
      neutral and action-relevant sentences, indicating that action information is
      incidentally activated. In contrast, apraxic participants showed delayed
      activation of manipulation-based action information during object identification
      when cued by neutral sentences. The magnitude of delayed activation in the
      neutral sentence condition was reliably predicted by lower scores on a test of
      gesture production to viewed objects, as well as by lesion loci in the inferior
      parietal and posterior temporal lobes. However, when cued by a sentence
      containing an action verb, apraxic participants showed fixation patterns that
      were statistically indistinguishable from non-apraxic controls. In support of
      grounded theories of cognition, these results suggest that apraxia and temporal
      parietal lesions may be associated with abnormalities in incidental activation of
      action information from objects. Further, they suggest that the previously
      observed facilitative role of action verbs in the retrieval of object-related
      action information extends to participants with apraxia.

PMID- 24746948
TI  - MicroRNA expression patterns of tumors in early-onset colorectal cancer patients.
AB  - BACKGROUND: The expression of microRNAs (miRNAs) may differ in tumors from
      patients with different ethnic origins and ages. The aims of the present study
      were to clarify the appropriate alterations of miRNA expression associated with
      the early stages of carcinogenesis in early-onset Turkish colorectal cancer (CRC)
      patients and to define specific biomarkers that could be used as new diagnostic
      and prognostic markers for this population. MATERIALS AND METHODS: The expression
      profiles of 38 different miRNAs associated with CRC were evaluated using miRNA
      polymerase chain reaction arrays in tumors and surgical margin tissue samples
      from 40 sporadic early-onset Turkish CRC patients. The relationships between the
      miRNA expression profiles and the characteristics of the tumors and patients were
      evaluated. RESULTS: The expression of miR-106a was found to be upregulated, and
      miR-143 and miR-125b levels were found to be downregulated in tumor tissues
      compared with the normal tissues. The high expression level of miR-106a (2.93
      fold; P = 0.031) and low expression level of miR-125b (2.42-fold; P = 0.063) were
      observed in tumors with lymph node metastases compared with the normal colorectal
      mucosa samples. However, the deregulation of these miRNAs was not significantly
      associated with survival (log-rank P > 0.05). CONCLUSIONS: The present results
      implied that miR-106a and the miR-125b were associated with the formation and
      invasion of colorectal tumors. Thus, these miRNAs might be used as significant
      prognostic factors and indicators of early-stage CRC. Further studies and
      validations are required; these miRNAs may provide novel molecular targets for
      CRC treatment.

PMID- 24746949
TI  - Margin index: a useful tool for the breast surgeon?
AB  - BACKGROUND: In breast conservation surgery (BCS) for breast cancer, the
      appropriate surgical margin is controversial. Margin index, a mathematical
      relationship between tumor size and closest margin, has been shown to be
      predictive of the probability of residual cancer after BCS for early stage breast
      cancer. We applied this tool to the same population of patients at our
      institution to evaluate its ability to predict residual disease after BCS.
      METHODS: We retrospectively reviewed a prospectively maintained database of women
      undergoing BCS between 1980 and 2010 at the University of Pennsylvania. A total
      of 246 women underwent re-excision because of close margins. Average margin index
      between groups with and without residual disease in the re-excision specimen was
      compared using the Student t-test. A receiver operating curve was created using
      logistic regression to assess the overall diagnostic ability of the margin index
      on the presence or absence of residual disease. RESULTS: Of patients who
      underwent re-excision, 29% of patients had residual disease. We analyzed several
      cutoff values for margin index, but none proved to be significant predictors of
      residual disease. Average margin index was significantly higher for patients
      without residual disease compared with patients with residual invasive cancer but
      not for patients with residual ductal carcinoma in situ. CONCLUSIONS: In women
      undergoing BCS for early stage breast cancer at our institution, margin index was
      not predictive of the presence of residual cancer on re-excision. We hypothesize
      that the predictive ability of a margin index is likely limited by several
      factors including the presence of ductal carcinoma in situ and the location and
      extent of the close margin.

PMID- 24746950
TI  - Aortic valve calcification is mediated by a differential response of aortic valve
      interstitial cells to inflammation.
AB  - BACKGROUND: Although calcific aortic stenosis is common, calcification of the
      other three heart valves is not. The aortic valve interstitial cell (VIC) has
      been implicated in the pathogenesis of aortic stenosis. Proinflammatory
      stimulation of aortic VICs induces an osteogenic and inflammatory phenotypic
      change. We hypothesized that the VICs of the other heart valves do not undergo
      these changes. Using isolated human VICs from normal aortic, mitral, pulmonary,
      and tricuspid valves, our purpose was to compare the osteogenic response to
      proinflammatory stimulation via toll-like receptor 4 (TLR-4). MATERIALS AND
      METHODS: Aortic, pulmonic, mitral, and tricuspid (n=4 for each valve type) VICs
      were isolated from hearts valves explanted from patients undergoing cardiac
      transplantation. Cells were cultured and grown to confluence in passage 2-6
      before treatment with Lipopolysaccharide (LPS) (100-200 ng/mL) for 24 or 48 h.
      Cells were characterized by immunofluorescent staining. TLR-4 expression was
      analyzed (immunoblotting, flow cytometry). Bone morphogenetic protein 2 and
      intercellular adhesion molecule 1 production were determined (immunoblotting).
      Monocyte chemoattractant protein 1 levels were determined by enzyme-linked
      immunosorbent assay. Statistics were by Mann-Whitney U test. RESULTS: TLR-4
      stimulation induced bone morphogenetic protein 2 production only in aortic VICs
      (P<0.05). Intra-cellular adhesion molecule 1 production and monocyte
      chemoattractant protein 1 secretion increased in a similar fashion among TLR-4
      stimulated VICs from all four valves. CONCLUSIONS: Proinflammatory stimulation
      induces an osteogenic phenotype in aortic VICs but not mitral, pulmonic, or
      tricuspid VICs. We conclude that this differential osteogenic response of aortic
      VICs contributes to the pathogenesis of calcific aortic stenosis.

PMID- 24746951
TI  - Delayed remote preconditioning induces cardioprotection: role of heme oxygenase
      1.
AB  - BACKGROUND: The role of heme oxygenase-1 (HO-1) in the cardioprotection induced
      by delayed remote ischemic preconditioning (DRIPC) has not been investigated.
      Therefore, this study was designed to investigate whether HO-1 is involved in
      DRIPC-mediated cardioprotection in an isolated perfused rat heart model.
      MATERIALS AND METHODS: Isolated rat hearts were subjected to 30 min ischemia
      followed by 60 min reperfusion. DRIPC (four cycles 5-min occlusion and 5-min
      reflow at the unilateral hind limb once per day for 1, 2, or 3 d before heart
      isolation, abbreviated as D1RIPC, D2RIPC, or D3RIPC respectively). Infarct size,
      myocardial troponin levels, and heart function were measured. The protein and
      messenger RNA levels of HO-1 were determined. RESULTS: DRIPC facilitated
      postischemic cardiac functional recovery and decreased cardiac enzyme release.
      The infarct size-limiting effect of DRIPC was more pronounced in the D3RIPC group
      (10.22 +/- 2.57%) than the D1RIPC group (22.34 +/- 4.02%, P < 0.001) or the
      D2RIPC group (14.60 +/- 3.13%, P = 0.034). These effects in the D1RIPC group
      could be blocked by Zinc Protoporphyrin IX (ZnPP) (an HO-1 specific inhibitor).
      DRIPC-mediated cardioprotection was associated with enhanced HO-1 protein
      expression (D1RIPC, 0.11 +/- 0.03; versus 0.15 +/- 0.06 in the D2RIPC group, P =
      0.06; versus 0.20 +/- 0.04 in the D3RIPC group, P = 0.04) and messenger RNA
      levels of HO-1 expression. CONCLUSIONS: Our findings suggest that HO-1 is
      involved in the cardioprotection induced by DRIPC, and that increase in the
      number of preconditioning stimuli may enhance cardioprotective effects
      accompanied with increased HO-1 level.

PMID- 24746952
TI  - Standardized and quality-assured video-recorded examination in undergraduate
      education: informed consent prior to surgery.
AB  - BACKGROUND: Communication skills combined with specialized knowledge are
      fundamental to the doctor-patient relationship in surgery. During a single
      station video-recorded objective structured clinical examination (VOSCE),
      students were tasked with obtaining informed consent. Our aim was to develop a
      standardized and quality-assured assessment method in undergraduate education.
      METHODS: One hundred fifty-five students in their fifth year of medical school
      (78 videos) participated in a summative VOSCE within the framework of the
      teaching module "Operative Medicine." They prepared for three clinical scenarios
      and the surgical procedures involved. The examination comprised participants
      having to obtain informed consent from simulated patients, video recording their
      performance. Students were assessed by two independent raters, the background of
      one of whom was nonsurgical. Results were statistically tested using SPSS.
      RESULTS: Students' scores were all beyond the pass mark of 70%, averaging 91.0%
      (+/-4.0%), 88.4% (+/-4.4%), and 87.0% (+/-4.7%) for the appendectomy,
      cholecystectomy, and inguinal hernia repair checklist, respectively. Most items
      (68%-89% of the checklists) were found to have fair to excellent discrimination
      values. Cronbach's alpha values ranged between 0.565 and 0.605 for the individual
      checklists. Interrater agreement was strong (Pearson correlation coefficient =
      0.80, P < 0.01; intraclass correlation coefficient 2.1 = 0.78). CONCLUSIONS: The
      VOSCE is both feasible and reliable as a method of assessing student
      communication skills and the application of clinical knowledge while obtaining
      informed consent in surgery. This method is efficient (flexible rating outside
      normal working hours possible with reductions in administrative load) and may be
      used for high-stakes evaluation of student performance.

PMID- 24746953
TI  - Investigating viability of intestine using spectroscopy: a pilot study.
AB  - BACKGROUND: The differentiation of "viable" from "nonviable" bowel remains a
      challenge in the treatment of acute mesenteric ischemia. In this study, diffuse
      reflectance spectroscopy (DRS) was used to investigate the viability of bowel
      tissue after ischemia and reperfusion in an animal model in vivo and in real
      time. METHODS: A total of 25 females Sprague-Dawley rats were divided into five
      groups based on different bowel ischemia times. In each study group for four of
      them, the superior mesenteric artery was occluded using a vascular clamp for a
      different period (i.e., 30, 45, 60, and 90 min; n = 5 for each group). Intestinal
      reperfusion was accomplished by releasing the clamps after the given occlusion
      period for each group. Spectra were acquired by gently touching the optical fiber
      probe to the bowel tissue before the induce ischemia, at the end of the induced
      ischemia, and after the reperfusion. The data acquired before the ischemia were
      used as a control group. Without occluding the superior mesenteric artery, the
      spectra were acquired on the bowel with the same time intervals of the
      experiments were used as a sham group (n = 5). Subsequently, the same bowel
      segments were sent for histopathologic examination. RESULTS: Based on the
      correlation between the spectra acquired from the bowel segments and the results
      from the histopathologic investigation, DRS is able to differentiate the
      histopathologic grading that appears when the Chiu/Park score >=5 (i.e., high
      level ischemic injury) than Chiu/Park score <5. Eight out of nine low-level
      ischemic injury tissue samples were correctly defined using the spectroscopic
      classification system. All eleven high-level ischemic injury tissues that were
      histopathologically assigned grade 5 and above were correctly defined using the
      spectroscopic classification system in the ischemia-reperfusion groups.
      CONCLUSIONS: DRS could potentially be used intraoperatively for the assessment of
      bowel viability in real time. These preliminary findings suggest that DRS has the
      potential to reduce unnecessary resection of viable tissue or insufficient
      resection of nonviable tissues may reduce the mortality and morbidity rates of
      intestinal ischemia-reperfusion as acute mesenteric ischemia.

PMID- 24746954
TI  - Discovering the structure of mathematical problem solving.
AB  - The goal of this research is to discover the stages of mathematical problem
      solving, the factors that influence the duration of these stages, and how these
      stages are related to the learning of a new mathematical competence. Using a
      combination of multivariate pattern analysis (MVPA) and hidden Markov models
      (HMM), we found that participants went through 5 major phases in solving a class
      of problems: A Define Phase where they identified the problem to be solved, an
      Encode Phase where they encoded the needed information, a Compute Phase where
      they performed the necessary arithmetic calculations, a Transform Phase where
      they performed any mathematical transformations, and a Respond Phase where they
      entered an answer. The Define Phase is characterized by activity in visual
      attention and default network regions, the Encode Phase by activity in visual
      regions, the Compute Phase by activity in regions active in mathematical tasks,
      the Transform Phase by activity in mathematical and response regions, and the
      Respond phase by activity in motor regions. The duration of the Compute and
      Transform Phases were the only ones that varied with condition. Two features
      distinguished the mastery trials on which participants came to understand a new
      problem type. First, the duration of late phases of the problem solution
      increased. Second, there was increased activation in the rostrolateral prefrontal
      cortex (RLPFC) and angular gyrus (AG), regions associated with metacognition.
      This indicates the importance of reflection to successful learning. 

PMID- 24746955
TI  - Selective attention to phonology dynamically modulates initial encoding of
      auditory words within the left hemisphere.
AB  - Selective attention to phonology, i.e., the ability to attend to sub-syllabic
      units within spoken words, is a critical precursor to literacy acquisition.
      Recent functional magnetic resonance imaging evidence has demonstrated that a
      left-lateralized network of frontal, temporal, and posterior language regions,
      including the visual word form area, supports this skill. The current event
      related potential (ERP) study investigated the temporal dynamics of selective
      attention to phonology during spoken word perception. We tested the hypothesis
      that selective attention to phonology dynamically modulates stimulus encoding by
      recruiting left-lateralized processes specifically while the information critical
      for performance is unfolding. Selective attention to phonology was captured by
      manipulating listening goals: skilled adult readers attended to either rhyme or
      melody within auditory stimulus pairs. Each pair superimposed rhyming and melodic
      information ensuring identical sensory stimulation. Selective attention to
      phonology produced distinct early and late topographic ERP effects during
      stimulus encoding. Data-driven source localization analyses revealed that
      selective attention to phonology led to significantly greater recruitment of left
      lateralized posterior and extensive temporal regions, which was notably
      concurrent with the rhyme-relevant information within the word. Furthermore,
      selective attention effects were specific to auditory stimulus encoding and not
      observed in response to cues, arguing against the notion that they reflect
      sustained task setting. Collectively, these results demonstrate that selective
      attention to phonology dynamically engages a left-lateralized network during the
      critical time-period of perception for achieving phonological analysis goals.
      These findings suggest a key role for selective attention in on-line phonological
      computations. Furthermore, these findings motivate future research on the role
      that neural mechanisms of attention may play in phonological awareness
      impairments thought to underlie developmental reading disabilities. 

PMID- 24746956
TI  - Contingency management for cocaine treatment: cash vs. vouchers.
AB  - The efficacy of contingency management (CM) for treating drug abuse is well
      supported. The most widely used form of CM is voucher-based reinforcement therapy
      (VBRT), where clients receive an escalating schedule of vouchers that can be
      redeemed for goods and services for meeting treatment goals. Though generally
      rejected due to concerns about potential harms to drug using participants,
      research suggests that cash may be a more effective reinforcer. This three-group
      randomized trial compared the efficacy of cash-based reinforcement therapy (CBRT)
      to VBRT and a non-CM condition on cocaine abstinence and treatment attendance;
      and examined whether CBRT resulted in greater levels of harm than VBRT. Findings
      indicated that the CBRT was as effective as VBRT when compared to the non-CM
      condition and that it did not increase rates of drug use, cravings, or high-risk
      behaviors. Future research should examine potential cost savings associated with
      a cash-based CM approach as this could have important implications for the wider
      adoption of the CM model. 

PMID- 24746957
TI  - Maximizing the power of principal-component analysis of correlated phenotypes in
      genome-wide association studies.
AB  - Many human traits are highly correlated. This correlation can be leveraged to
      improve the power of genetic association tests to identify markers associated
      with one or more of the traits. Principal component analysis (PCA) is a useful
      tool that has been widely used for the multivariate analysis of correlated
      variables. PCA is usually applied as a dimension reduction method: the few top
      principal components (PCs) explaining most of total trait variance are tested for
      association with a predictor of interest, and the remaining components are not
      analyzed. In this study we review the theoretical basis of PCA and describe the
      behavior of PCA when testing for association between a SNP and correlated traits.
      We then use simulation to compare the power of various PCA-based strategies when
      analyzing up to 100 correlated traits. We show that contrary to widespread
      practice, testing only the top PCs often has low power, whereas combining signal
      across all PCs can have greater power. This power gain is primarily due to
      increased power to detect genetic variants with opposite effects on positively
      correlated traits and variants that are exclusively associated with a single
      trait. Relative to other methods, the combined-PC approach has close to optimal
      power in all scenarios considered while offering more flexibility and more
      robustness to potential confounders. Finally, we apply the proposed PCA strategy
      to the genome-wide association study of five correlated coagulation traits where
      we identify two candidate SNPs that were not found by the standard approach. 

PMID- 24746958
TI  - Describing sequencing results of structural chromosome rearrangements with a
      suggested next-generation cytogenetic nomenclature.
AB  - With recent rapid advances in genomic technologies, precise delineation of
      structural chromosome rearrangements at the nucleotide level is becoming
      increasingly feasible. In this era of "next-generation cytogenetics" (i.e., an
      integration of traditional cytogenetic techniques and next-generation
      sequencing), a consensus nomenclature is essential for accurate communication and
      data sharing. Currently, nomenclature for describing the sequencing data of these
      aberrations is lacking. Herein, we present a system called Next-Gen Cytogenetic
      Nomenclature, which is concordant with the International System for Human
      Cytogenetic Nomenclature (2013). This system starts with the alignment of
      rearrangement sequences by BLAT or BLAST (alignment tools) and arrives at a
      concise and detailed description of chromosomal changes. To facilitate usage and
      implementation of this nomenclature, we are developing a program designated
      BLA(S)T Output Sequence Tool of Nomenclature (BOSToN), a demonstrative version of
      which is accessible online. A standardized characterization of structural
      chromosomal rearrangements is essential both for research analyses and for
      application in the clinical setting. 

PMID- 24746960
TI  - Switching between self-renewal and lineage commitment of human induced
      pluripotent stem cells via cell-substrate and cell-cell interactions on a
      dendrimer-immobilized surface.
AB  - Understanding mechanisms that govern cell fate determination of human induced
      pluripotent stem cells (hiPSCs) could assist in maintenance of the
      undifferentiated state during cell expansion. We used polyamidoamine dendrimer
      surfaces with first-generation (G1), third-generation (G3) and fifth-generation
      (G5) of dendron structure in cultures of hiPSCs with SNL feeder cells. Cells on
      the G1 surface formed tightly packed colony with close cell-cell contacts during
      division and migration; those on the G3 surface exhibited loose or dispersed
      colony pattern by enhanced migration. On the G5 surface, formation of aggregated
      colony with ring-like structures occurred spontaneously. We found that the
      substrate-adsorbed fibronectin and feeder cell-secreted fibronectin appeared
      elevated levels with the varied generation numbers of dendrimer surfaces. This
      subsequently resulted in cell migration and in activation of paxillin of hiPSCs.
      Location-dependent expression of Rac1 induced rearrangement of E-cadherin
      mediated cell-cell interactions on dendrimer surfaces, and was associated with
      alterations in the cell and colony morphology, and migratory behavior.
      Furthermore, caspase-3 occurred in apoptotic cells on dendrimer surfaces,
      concomitant with the loss of E-cadherin-mediated cell-cell interactions. Cells on
      the G1 surface were maintained in an undifferentiated state, while those on the
      G5 surface exhibited the early commitment to differentiation toward endodermal
      fates. We conclude that morphological changes associated with altered migration
      on the dendrimer surfaces were responsible for the coordinated regulation of
      balance between cell-cell and cell-substrate interactions, thereby switching
      their transition from self-renewal state to early endoderm differentiation in
      hiPSCs. 

PMID- 24746959
TI  - Recurrent CNVs and SNVs at the NPHP1 locus contribute pathogenic alleles to
      Bardet-Biedl syndrome.
AB  - Homozygosity for a recurrent 290 kb deletion of NPHP1 is the most frequent cause
      of isolated nephronophthisis (NPHP) in humans. A deletion of the same genomic
      interval has also been detected in individuals with Joubert syndrome (JBTS), and
      in the mouse, Nphp1 interacts genetically with Ahi1, a known JBTS locus. Given
      these observations, we investigated the contribution of NPHP1 in Bardet-Biedl
      syndrome (BBS), a ciliopathy of intermediate severity. By using a combination of
      array-comparative genomic hybridization, TaqMan copy number assays, and
      sequencing, we studied 200 families affected by BBS. We report a homozygous NPHP1
      deletion CNV in a family with classical BBS that is transmitted with autosomal
      recessive inheritance. Further, we identified heterozygous NPHP1 deletions in two
      more unrelated persons with BBS who bear primary mutations at another BBS locus.
      In parallel, we identified five families harboring an SNV in NPHP1 resulting in a
      conserved missense change, c.14G>T (p.Arg5Leu), that is enriched in our Hispanic
      pedigrees; in each case, affected individuals carried additional bona fide
      pathogenic alleles in another BBS gene. In vivo functional modeling in zebrafish
      embryos demonstrated that c.14G>T is a loss-of-function variant, and suppression
      of nphp1 in concert with each of the primary BBS loci found in our NPHP1-positive
      pedigrees exacerbated the severity of the phenotype. These results suggest that
      NPHP1 mutations are probably rare primary causes of BBS that contribute to the
      mutational burden of the disorder. 

PMID- 24746961
TI  - The effect of thick fibers and large pores of electrospun poly(epsilon
      caprolactone) vascular grafts on macrophage polarization and arterial
      regeneration.
AB  - The vascular grafts prepared by electrospinning often have relatively small
      pores, which limit cell infiltration into the grafts and hinder the regeneration
      and remodeling of the grafts into neoarteries. To overcome this problem,
      macroporous electrospun polycaprolactone (PCL) scaffolds with thicker fibers (5-6
      MUm) and larger pores (~30 MUm) were fabricated in the present study. In vitro
      cell culture indicated that macrophages cultured on thicker-fiber scaffolds
      tended to polarize into the immunomodulatory and tissue remodeling (M2)
      phenotype, while those cultured on thinner-fiber scaffolds expressed
      proinflammatory (M1) phenotype. In vivo implantation by replacing rat abdominal
      aorta was performed and followed up for 7, 14, 28 and 100 d. The results
      demonstrated that the macroporous grafts markedly enhanced cell infiltration and
      extracellular matrix (ECM) secretion. All grafts showed satisfactory patency for
      up to 100 days. At day 100, the endothelium coverage was complete, and the
      regenerated smooth muscle layer was correctly organized with abundant ECM similar
      to those in the native arteries. More importantly, the regenerated arteries
      demonstrated contractile response to adrenaline and acetylcholine-induced
      relaxation. Analysis of the cellularization process revealed that the thicker
      fiber scaffolds induced a large number of M2 macrophages to infiltrate into the
      graft wall. These macrophages further promoted cellular infiltration and
      vascularization. In conclusion, the present study confirmed that the scaffold
      structure can regulate macrophage phenotype. Our thicker-fiber electrospun PCL
      vascular grafts could enhance the vascular regeneration and remodeling process by
      mediating macrophage polarization into M2 phenotype, suggesting that our
      constructs may be a promising cell-free vascular graft candidate and are worthy
      for further in vivo evaluation. 

PMID- 24746962
TI  - Prussian blue coated gold nanoparticles for simultaneous photoacoustic/CT bimodal
      imaging and photothermal ablation of cancer.
AB  - The combination of CT imaging and photoacoustic (PA) imaging represents not only
      high resolution and ease of forming 3D visual image for locating tissues of
      interest, but also good soft tissue contrast and excellent high sensitivity,
      which is very beneficial to the precise guidance for photothermal therapy (PTT).
      The near infrared (NIR) absorbing Au nanostructures take advantages to operate as
      a CT contrast agent due to high absorption coefficient of X-ray and outstanding
      biocompatibility, but show obvious deficiency for PA imaging and PTT because of
      low photostability. Attacking this problem head on, the Au nanoparticles (NPs)
      were coated with Prussian blue (PB) which is a typical FDA-approved drug in
      clinic for safe and effective treatment of radioactive exposure. The obtained
      core/shell NPs of Au@PB NPs of 17.8 +/- 2.3 nm were found to be an excellent
      photoabsorbing agent for both PTT and PA imaging due to high photostability and
      high molar extinction coefficient in NIR region. Their gold core of 9.1 +/- 0.64
      nm ensured a remarkable contrast enhancement for CT imaging. Through a one-time
      treatment of NIR laser irradiation after intravenous injection of Au@PB NPs, 100
      mm(3) sized tumors in nude mice could be completely ablated without recurrence.
      Such versatile nanoparticles integrating effective cancer diagnosis with
      noninvasive therapy might bring opportunities to future cancer therapy. 

PMID- 24746963
TI  - A tumor-targeting near-infrared laser-triggered drug delivery system based on
      GO@Ag nanoparticles for chemo-photothermal therapy and X-ray imaging.
AB  - In this study, a GO@Ag nanocomposite was synthesized by chemical deposition of Ag
      nanoparticles onto graphene oxide (GO) through a hydro thermal reaction, and
      doxorubicin (DOX), one of the most effective drugs against a wide range of
      cancers, was employed as the model drug and linked to GO@Ag via ester bonds with
      a very high drug loading efficiency (~82.0%, weight ratio of DOX/GO@Ag), then
      GO@Ag-DOX was functionalized by DSPE-PEG2000-NGR, giving GO@Ag-DOX with active
      tumor-targeting capacity and excellent stability in physiological solutions. The
      release profiles of DOX from GO@Ag-DOX-NGR showed strong dependences on near
      infrared (NIR) laser and the SPR effect of Ag nanoparticles. Compared with free
      DOX in an in vivo murine tumor model, GO@Ag-DOX-NGR afforded much higher
      antitumor efficacy without obvious toxic effects to normal organs owing to 8.4
      fold higher DOX uptake of tumor and 1.7-fold higher DOX released in tumor with
      NIR laser than the other tissues. Besides, in this work, GO@Ag-DOX-NGR not only
      served as a powerful tumor diagnostic X-ray contrast agent, but also as a strong
      agent for photothermal ablation of tumor, the ability of GO@Ag-DOX-NGR
      nanoparticles to combine the local specific chemotherapy with external
      photothermal therapy (PTT) significantly improved the therapeutic efficacy. GO@Ag
      DOX-NGR showed excellent chem-photothermal therapeutic efficacy, tumor-targeting
      property, NIR laser-controlled drug releasing function and X-ray imaging ability,
      demonstrating that there is a great potential of GO@Ag-DOX-NGR for cancer
      diagnosis and therapy. 

PMID- 24746964
TI  - A PNIPAAm-based thermosensitive hydrogel containing SWCNTs for stem cell
      transplantation in myocardial repair.
AB  - Poly (N-isopropylacrylamide) (PNIPAAm) hydrogel was a widely used carrier in
      therapeutic agent delivery. However, its bioactivities for encapsulated cells
      were not satisfactory. In the study, we aimed to determine whether modification
      with single-wall carbon nanotubes (SWCNTs) could improve the bioactivitis,
      especially supportive adhesion of PNIPAAm to encapsulated cells and favor their
      efficacy in myocardial repair. A thermosensitive SWCNTs-modified PNIPAAm hydrogel
      (PNIPAAm/SWCNTs) were prepared by incorporating the SWCNTs into base PNIPAAm
      hydrogel. The bioactivities of the resulted hydrogel to brown adipose-derived
      stem cells (BASCs) were evaluated and compared with the base PNIPAAm hydrpgel in
      vitro. Then, the PNIPAAm-containing hydrogel was used as carrier for
      imtromyocardial delivery of BASCs in rats with myocardial infarction. The
      efficacy of PNIPAAm/SWCNTs hydrogel in stem cell-based myocardial repair was
      systematically evaluated. In vitro study showed that the PNIPAAm/SWCNTs hydrogel
      demonstrated significantly higher bioactivities to encapsulated BASCs compared
      with onefold PNIPAAm hydrogel, including promoting cell adhesion and
      proliferation. When used as carrier for intramyocardial delivery of BASCs after
      myocardial infarction, the PNIPAAm/SWCNTs hydrogel significantly enhanced the
      engraftment of seeding cells in infarct myocardium and augmented their
      therapeutic efficacies in myocardial infarction (MI). The data provided a
      supportive evidence for the myocardial application of the SWCNTs-modified
      hydrogel and offered a new perspective in development or improvement of cardiac
      tissue engineering scaffold. 

PMID- 24746965
TI  - Tumor-penetrating codelivery of siRNA and paclitaxel with ultrasound-responsive
      nanobubbles hetero-assembled from polymeric micelles and liposomes.
AB  - Drug resistance is a big problem in systemic chemotherapy of hepatocellular
      carcinoma (HCC), and nanomedicines loaded with both chemotherapeutic agents (e.g.
      paclitaxel, PTX) and siRNA's targeting antiapoptosis genes (e.g. BCL-2) possess
      the advantages to simultaneously overcome the efflux pump-mediated drug
      resistance and antiapoptosis-related drug resistance. However, tumor-penetrating
      drug delivery with this type of nanomedicines is extremely difficult due to their
      relatively big size compared to the single drug-loaded nanomedicines. Aiming at
      address this problem, US-responsive nanobubbles encapsulating both anti-cancer
      drug paclitaxel (PTX) and siRNA (PTX-NBs/siRNA) for HCC treatment were developed
      by hetero-assembly of polymeric micelles and liposomes in the present study.
      Utilizing an external low-frequency US force imposed to the tumor site, effective
      tumor-penetrating codelivery of siRNA and PTX was achieved via tail vein
      injection of PTX-NBs/siRNA into nude mice bearing human HepG2 xerografts.
      Consequently, the PTX treatment-inducible antiapoptosis in HepG2 cells was
      effectively suppressed by the codelivered siRNA targeting an antiapoptosis gene
      (BCL-2 siRNA) during chemotherapy. Owing to the synergistic anti-cancer effect of
      two therapeutic agents, tumor growth was completely inhibited using low-dose PTX
      in animal study. Our results highlight the great potential of this type of US
      responsive hetero-assemblies carrying both anti-cancer drug and siRNA as an
      effective nanomedicinal system for HCC therapy. 

PMID- 24746966
TI  - Encapsulating tantalum oxide into polypyrrole nanoparticles for X-ray
      CT/photoacoustic bimodal imaging-guided photothermal ablation of cancer.
AB  - A nanotheranostic agent has been readily fabricated by encapsulating tantalum
      oxide (TaOx) nanoparticles (NPs) into polypyrrole (PPy) NPs via a facile one-step
      chemical oxidation polymerization for bimodal imaging guided photothermal
      ablation of tumor. It was proved that the obtained composite nanoparticles
      (TaOx@PPy NPs) with an average diameter around 45 nm could operate as an
      efficient bimodal contrast agent to simultaneously enhance X-ray CT and
      photoacoustic (PA) imaging greatly in vivo. Systemically administered TaOx@PPy
      NPs could passively accumulate at the tumor site during the blood circulation,
      which was proved by both CT and PA imaging. In addition, the in vivo therapeutic
      examinations showed that TaOx@PPy NPs exhibited significant photothermal
      cytotoxicity under near infrared laser irradiation. The tumor growth inhibition
      was evaluated to be 66.5% for intravenously injection and 100% for intratumoral
      injection, respectively. This versatile agent can be developed as a smart and
      promising nanoplatform that integrates multiple capabilities for both accurate
      diagnosing and precise locating of cancerous tissue, as well as effective
      photoablation of tumor. 

PMID- 24746967
TI  - Bioengineered human tumor within a bone niche.
AB  - Monolayer cultures of tumor cells and animal studies have tremendously advanced
      our understanding of cancer biology. However, we often lack animal models for
      human tumors, and cultured lines of human cells quickly lose their cancer
      signatures. In recent years, simple 3D models for cancer research have emerged,
      including cell culture in spheroids and on biomaterial scaffolds. Here we
      describe a bioengineered model of human Ewing's sarcoma that mimics the native
      bone tumor niche with high biological fidelity. In this model, cancer cells that
      have lost their transcriptional profiles after monolayer culture re-express genes
      related to focal adhesion and cancer pathways. The bioengineered model recovers
      the original hypoxic and glycolytic tumor phenotype, and enables re-expression of
      angiogenic and vasculogenic mimicry features that favor tumor adaptation. We
      propose that differentially expressed genes between the monolayer cell culture
      and native tumor environment are potential therapeutic targets that can be
      explored using the bioengineered tumor model. 

PMID- 24746968
TI  - Differentiation of lung stem/progenitor cells into alveolar pneumocytes and
      induction of angiogenesis within a 3D gelatin--microbubble scaffold.
AB  - The inability to adequately vascularize tissues in vitro or in vivo is a major
      challenge in lung tissue engineering. A method that integrates stem cell research
      with 3D-scaffold engineering may provide a solution. We have successfully
      isolated mouse pulmonary stem/progenitor cells (mPSCs) by a two-step procedure
      and fabricated mPSC-compatible gelatin/microbubble-scaffolds using a 2-channel
      fluid jacket microfluidic device. We then integrated the cells and the scaffold
      to construct alveoli-like structures. The mPSCs expressed pro-angiogenic factors
      (e.g., b-FGF and VEGF) and induced angiogenesis in vitro in an endothelial cell
      tube formation assay. In addition, the mPSCs were able to proliferate along the
      inside of the scaffolds and differentiate into type-II and type-I pneumocytes The
      mPSC-seeded microbubble-scaffolds showed the potential for blood vessel formation
      in both a chick chorioallantoic membrane (CAM) assay and in experiments for
      subcutaneous implantation in severe combined immunodeficient (SCID) mice. Our
      results demonstrate that lung stem/progenitor cells together with gelatin
      microbubble-scaffolds promote angiogenesis as well as the differentiation of
      alveolar pneumocytes, resulting in an alveoli-like structure. These findings may
      help advance lung tissue engineering. 

PMID- 24746969
TI  - Visible-light-excited and europium-emissive nanoparticles for highly-luminescent
      bioimaging in vivo.
AB  - Europium(III)-based material showing special milliseconds photoluminescence
      lifetime has been considered as an ideal time-gated luminescence probe for
      bioimaging, but is still limited in application in luminescent small-animal
      bioimaging in vivo. Here, a water-soluble, stable, highly-luminescent nanosystem,
      Ir-Eu-MSN (MSN = mesoporous silica nanoparticles, Ir-Eu = [Ir(dfppy)2(pic
      OH)]3Eu.2H2O, dfppy = 2-(2,4-difluorophenyl)pyridine, pic-OH = 3-hydroxy-2
      carboxypyridine), was developed by an in situ coordination reaction to form an
      insoluble dinuclear iridium(III) complex-sensitized-europium(III) emissive
      complex within mesoporous silica nanoparticles (MSNs) which had high loading
      efficiency. Compared with the usual approach of physical adsorption, this in-situ
      reaction strategy provided 20-fold the loading efficiency (43.2%) of the
      insoluble Ir-Eu complex in MSNs. These nanoparticles in solid state showed bright
      red luminescence with high quantum yield of 55.2%, and the excitation window
      extended up to 470 nm. These Ir-Eu-MSN nanoparticles were used for luminescence
      imaging in living cells under excitation at 458 nm with confocal microscopy,
      which was confirmed by flow cytometry. Furthermore, the Ir-Eu-MSN nanoparticles
      were successfully applied into high-contrast luminescent lymphatic imaging in
      vivo under low power density excitation of 5 mW cm(-2). This synthetic method
      provides a universal strategy of combining hydrophobic complexes with hydrophilic
      MSNs for in vivo bioimaging. 

PMID- 24746970
TI  - Reply to E. David Crawford and Bo-Eric Persson's letter to the editor re: Giorgio
      Gandaglia, Maxine Sun, Jim C. Hu, et al. Gonadotropin-releasing hormone agonists
      and acute kidney injury in patients with prostate cancer. Eur Urol. In press.
      http://dx.doi.org/10.1016/j.eururo.2014.01.026.

PMID- 24746971
TI  - Assessment of the impact of targeted therapy on metastatic bone disease in renal
      cancer.

PMID- 24746972
TI  - Postoperative ileus after radical cystectomy: looking for answers to an age-old
      problem.

PMID- 24746973
TI  - Racial variation in prostate cancer upgrading and upstaging among men with low
      risk clinical characteristics.
AB  - BACKGROUND: African American (AA) men suffer a higher prostate cancer (PCa)
      burden than other groups. OBJECTIVE: We aim to determine the impact of race on
      the risk of upgrading, upstaging, and positive surgical margins (PSM) at radical
      prostatectomy (RP) among men eligible for active surveillance. DESIGN, SETTING,
      AND PARTICIPANTS: We studied men with low-risk PCa treated with RP at two
      centers. Low clinical risk was defined by National Comprehensive Cancer Network
      criteria. Outcome variables were upgrading, upstaging, and PSMs at surgery.
      Associations between race and the outcomes were evaluated with logistic
      regression adjusted for age, relationship status, diagnostic prostate-specific
      antigen level, percentage of positive biopsy cores, surgical approach, year of
      diagnosis, and clinical site. RESULTS AND LIMITATIONS: Of 9304 men diagnosed with
      PCa, 4231 were low risk and underwent RP within 1 yr. Men were categorized as AA
      (n=273; 6.5%), Caucasian (n=3771; 89.1%), or other racial/ethnic group (Other;
      n=187; 4.4%). AA men had a significantly younger mean age (58.7 yr; standard
      deviation: +/-7.06), and fewer (85%) were married or had a partner. Upgrading
      (34%) and upstaging (13%) rates did not significantly differ among the groups.
      The PSM rate was significantly higher in AA men (31%) than in the Caucasian (21%)
      and Other (20%) groups (p<0.01). We found an association between race group and
      PSM rate (p<0.03), with higher odds of PSMs in AA men versus Caucasian men (odds
      ratio [OR]: 1.64; 95% confidence interval [CI], 1.08-2.47). No statistically
      significant associations between race and rates of upgrading and upstaging were
      found. This study was limited by the relatively low proportion of AA men in the
      cohort. CONCLUSIONS: Among clinically low-risk men who underwent RP, AA men had a
      higher likelihood of PSMs compared with Caucasian men. We did not find
      statistically significantly different rates of upgrading and upstaging between
      the race groups. PATIENT SUMMARY: We analyzed two large groups of men with what
      appeared to be low-risk prostate cancer based on the initial biopsy findings. The
      likelihood of finding worse disease (higher grade or stage) at the time of
      surgery was similar across different racial groups.

PMID- 24746974
TI  - Consuming a mixed diet enriched with lupin protein beneficially affects plasma
      lipids in hypercholesterolemic subjects: a randomized controlled trial.
AB  - BACKGROUND & AIMS: The objectives of this study were to assess whether 25 g/d
      lupin protein, integrated into a mixed diet, might affect cardiovascular risk
      factors and whether l-arginine was responsible for these effects. METHODS:
      Seventy-two hypercholesterolemic subjects participated in the randomized,
      controlled, double-blind three-phase crossover study. They were assigned to three
      diets with 25 g/d lupin protein (LP), milk protein (MP) or milk protein plus 1.6
      g/d arginine (MPA) each for 28 d in a random order interrupted by 6-week washout
      periods. Lupin protein and the comparator milk protein were incorporated into
      complex food products (bread, roll, sausage, and vegetarian spread). Arginine was
      administered via capsules. Sixty-eight subjects were included in final analyses.
      RESULTS: Compared with MP, LDL cholesterol was significantly lower after LP.
      Compared with MP and MPA, homocysteine was significantly lower after LP. Compared
      with baseline, concentrations of total, LDL, and HDL cholesterol significantly
      decreased after LP and MPA. Triacylglycerols and uric acid significantly
      decreased after LP. The relative changes in total and LDL cholesterol were
      significantly greater for subjects with severe hypercholesterolemia (>6.6 mmol/L)
      than those with moderate hypercholesterolemia (5.2-6.6 mmol/L). CONCLUSIONS: The
      present study showed for the first time that incorporation of 25 g/d of lupin
      protein into a variety of complex food products lowers total and LDL cholesterol,
      triacylglycerols, homocysteine, and uric acid in hypercholesterolemic subjects.
      The hypocholesterolemic effect is stronger in subjects with severe
      hypercholesterolemia. Arginine might be responsible for some, but not all of the
      beneficial effects of lupin protein. This trial was registered at
      http://clinicaltrials.gov (study ID number NCT01598649).

PMID- 24746975
TI  - A longer time of exposure to antiretroviral therapy improves selenium levels.
AB  - BACKGROUND & AIMS: Selenium is an essential mineral for immunological function,
      performing crucial functions at the cellular level. This micronutrient has been
      determined to be frequently deficient in HIV infected patients, with correlations
      between reduced immunological function and greater susceptibility to
      opportunistic infections. Our aim was to evaluate the influence of time of
      exposure to antiretroviral therapy (ART) on the biochemical profile of selenium
      in HIV-infected patients. METHODS: We performed a cross-sectional study on 50 HIV
      positive men with different quantitations of viral load and CD4+ T cells, who
      were either receiving or not receiving ART. Dual energy X-ray absorptiometry
      (DXA) to determine body composition, biochemical analysis of selenium and
      albumin, anthropometric measurements were performed. The subjects were divided
      into groups according to the use of ART or not: The Control Group (CG) was 10
      treatment-naive volunteers, Group G < 2 was 20 volunteers on ART for less than 2
      years, and Group G > 2 was 20 volunteers on ART for >2 years. RESULTS: The body
      mass index showed that all subjects were of normal weight. The group with a
      longer time of exposure to ART (G > 2) had undetectable viremia and a higher CD4+
      T cell count: 593.1 +/- 234.6 mm(3). Selenium values (MUg/L) were 55.9 +/- 11.9
      for CG, 52.1 +/- 10.5 for G < 2, and 66.9 +/- 20.8 for G > 2, with a significant
      difference between groups G < 2 and G > 2 (p < 0.05), and only G > 2 showed
      normal selenium values. CONCLUSIONS: Most of the men studied showed selenium
      deficiency, except for the subjects with a longer exposure to antiretroviral
      treatment. Thus, an adequate selenium concentration is related to better control
      of virology and of immunologic function.

PMID- 24746976
TI  - Effects of an oral nutritional supplement containing eicosapentaenoic acid on
      nutritional and clinical outcomes in patients with advanced non-small cell lung
      cancer: randomised trial.
AB  - BACKGROUND: Nutritional interventions have shown increased energy intake but not
      improvement in health-related quality of life (HRQL) or prognosis in non small
      cell lung cancer (NSCLC) patients. Eicosapentaenoic acid has been proposed to
      have anti-inflammatory, anticachectic and antitumoural effects. OBJECTIVE: To
      compare the effect of an oral EPA enriched supplement with an isocaloric diet on
      nutritional, clinical and inflammatory parameters and HRQL in advanced NSCLC
      patients. DESIGN: Patients with advanced NSCLC were randomized to receive diet
      plus oral nutritional supplement containing EPA (ONS-EPA) or only isocaloric diet
      (C). All patients received paclitaxel and cisplatin/carboplatin treatment.
      Weight, body composition, dietary intake, inflammatory parameters and HRQL were
      assessed at baseline and after the first and second cycles of chemotherapy.
      Response to chemotherapy and survival were evaluated. RESULTS: Ninety two
      patients were analysed (46 ONS-EPA,46 C). ONS-EPA group had significantly greater
      energy (p < 0.001) and protein (p < 0.001) intake compared with control. Compared
      with baseline, patients receiving the ONS-EPA gained 1.6 +/- 5 kg of lean body
      mass (LBM) compared with a loss of -2.0 +/- 6 kg in the control (p = 0.01).
      Fatigue, loss of appetite and neuropathy decreased in the ONS-EPA group (p <=
      0.05). There was no difference in response rate or overall survival between
      groups. CONCLUSION: Patients with NSCLC receiving ONS-EPA significantly improves
      energy and protein intake, body composition. and decreased fatigue, loss of
      appetite and neuropathy. Registered with ClinicalTrials.gov (NCT01048970).

PMID- 24746977
TI  - Physical exercise antagonizes clinical and anatomical features characterizing
      Lieber-DeCarli diet-induced obesity and related metabolic disorders.
AB  - BACKGROUND & AIMS: Lieber-DeCarli diet has been used to induce obesity and non
      alcoholic steatohepatitis (NASH). As scarce anatomical and clinical-related
      information on this diet model exists and being exercise an advised strategy to
      counteract metabolic diseases, we aimed to analyze the preventive (voluntary
      physical activity - VPA) and therapeutic (endurance training - ET) effect of
      exercise on clinical/anatomical features of rats fed with Lieber-DeCarli diet.
      METHODS: In the beginning of the protocol, Sprague-Dawley rats were divided into
      standard-diet sedentary (SS, n = 20), standard-diet VPA (SVPA, n = 10), high-fat
      diet sedentary (HS, n = 20) and high-fat diet VPA (HVPA, n = 10) groups. After 9
      weeks, half (n = 10) of SS and HS groups were engaged in an ET program (8 wks/5
      d/wk/60 min/day). At this time, a blood sample was collected for biochemical
      analysis. At the end of protocol (17-weeks) anatomic measures were assessed.
      Heart, liver, femur and visceral fat were weighted and blood was collected again.
      Liver section was used for histopathological examination. RESULTS: At 17-weeks,
      high-fat diet increased visceral adiposity (HS vs. SS), which was counteracted by
      both exercises. However, ET was the only intervention able to diminished obesity
      related measures and the histological features of NASH. Moreover, blood analysis
      at 9 weeks showed that high-fat diet increased ALT, AST, cholesterol and HDL
      while VLDL and TG levels were decreased (HS vs. SS). Notably, although these
      parameters were counteracted after 9-weeks of VPA, they were transitory and not
      observed after 17-weeks. CONCLUSIONS: ET used as a therapeutic tool mitigated the
      clinical/anatomical-related features induced by Liber-DeCarli diet, thus possibly
      contributing to control obesity and metabolic disorders.

PMID- 24746978
TI  - Incidental adrenal pheochromocytoma.

PMID- 24746979
TI  - Editorial comment.

PMID- 24746980
TI  - Role of anti-inflammatory adipokines in obesity-related diseases.
AB  - Obesity results in many health complications. Accumulating evidence indicates
      that the obese state is characterized by chronic low-grade inflammation, thereby
      leading to the initiation and progression of obesity-related disorders such as
      type 2 diabetes, hypertension, cardiovascular disease, and atherosclerosis. Fat
      tissue releases numerous bioactive molecules, called adipokines, which affect
      whole-body homeostasis. Most adipokines are proinflammatory, whereas a small
      number of anti-inflammatory adipokines including adiponectin exert beneficial
      actions on obese complications. The dysregulated production of adipokines seen in
      obesity is linked to the pathogenesis of various disease processes. In this
      review we focus on the role of the anti-inflammatory adipokines that are of
      current interest in the setting of obesity-linked metabolic and cardiovascular
      diseases. 

PMID- 24746981
TI  - The impact of assisted reproductive technologies on intra-uterine growth and
      birth defects in singletons.
AB  - Pooled odds ratios from meta-analyses of infants born following assisted
      reproductive technologies (ART) compared with non-ART singletons show increases
      in low birth weight, preterm birth, small for gestational age, and birth defects.
      Although there have been small reductions in recent data, odds associated with
      these outcomes are still higher for ART singletons. Both ART procedures and
      underlying infertility contribute to these increased risks. Outcomes appear
      better for frozen-thawed compared with fresh embryo transfers, but are poorer
      than for non-ART infants. There is a concerning increase in large-for-gestational
      age infants born following frozen-thawed embryo transfer and limited data on the
      effects of embryo vitrification used instead of slow-freezing techniques. Using
      large datasets, we now need to investigate risks of individual birth defects and
      disentangle the inter-related effects of different types of infertility and the
      multiple aspects of ART. Greater understanding of the causes of adverse ART
      outcomes and identification of modifiable risk factors may lead to further
      reductions in the disparities in outcome between ART and non-ART infants. 

PMID- 24746982
TI  - Feeding induces translocation of vacuolar proton ATPase and pendrin to the
      membrane of leopard shark (Triakis semifasciata) mitochondrion-rich gill cells.
AB  - In this study we characterized mitochondrion-rich (MR) cells and regulation of
      acid/base (A/B) relevant ion-transporting proteins in leopard shark (Triakis
      semifasciata) gills. Immunohistochemistry revealed that leopard shark gills
      posses two separate cell populations that abundantly express either Na+/K+-ATPase
      (NKA) or V-H+-ATPase (VHA), but not both ATPases together. Co-immunolocalization
      with mitochondrial Complex IV demonstrated, for the first time in shark gills,
      that both NKA- and VHA-rich cells are also MR cells, and that all MR cells are
      either NKA- or VHA-rich cells. Additionally we localized the anion exchanger
      pendrin to VHA-rich cells, but not NKA-rich cells. In starved sharks, VHA was
      localized throughout the cell cytoplasm and pendrin was present at the apical
      pole (but not in the membrane). However, in a significant number of gill cells
      from fed leopard sharks, VHA translocated to the basolateral membrane (as
      previously described in dogfish), and pendrin translocated to the apical
      membrane. Our results highlight the importance of translocation of ion
      transporting proteins to the cell membrane as a regulatory mechanism for A/B
      regulation.

PMID- 24746983
TI  - Expressional regulation of key hepatic enzymes of intermediary metabolism in
      European seabass (Dicentrarchus labrax) during food deprivation and refeeding.
AB  - We hypothesized that the analysis of mRNA level and activity of key enzymes in
      amino acid and carbohydrate metabolism in a feeding/fasting/refeeding setting
      could improve our understanding of how a carnivorous fish, like the European
      seabass (Dicentrarchus labrax), responds to changes in dietary intake at the
      hepatic level. To this end cDNA fragments encoding genes for cytosolic and
      mitochondrial alanine aminotransferase (cALT; mALT), pyruvate kinase (PK),
      glucose 6-phosphate dehydrogenase (G6PDH) and 6-phosphogluconate dehydrogenase
      (6PGDH) were cloned and sequenced. Measurement of mRNA levels through
      quantitative real-time PCR performed in livers of fasted seabass revealed a
      significant increase in cALT (8.5-fold induction) while promoting a drastic 45
      fold down-regulation of PK in relation to the levels found in fed seabass. These
      observations were corroborated by enzyme activity meaning that during food
      deprivation an increase in the capacity of pyruvate generation happened via
      alanine to offset the reduction in pyruvate derived via glycolysis. After a 3-day
      refeeding period cALT returned to control levels while PK was not able to
      rebound. No alterations were detected in the expression levels of G6PDH while
      6PGDH was revealed to be more sensitive specially to fasting, as confirmed by a
      significant 5.7-fold decrease in mRNA levels with no recovery after refeeding.
      Our results indicate that in early stages of refeeding, the liver prioritized the
      restoration of systemic normoglycemia and replenishment of hepatic glycogen. In a
      later stage, once regular feeding is re-established, dietary fuel may then be
      channeled to glycolysis and de novo lipogenesis. 

PMID- 24746984
TI  - Structure and mechanism of ATP-dependent phospholipid transporters.
AB  - BACKGROUND: ATP-binding cassette (ABC) transporters and P4-ATPases are two large
      and seemingly unrelated families of primary active pumps involved in moving
      phospholipids from one leaflet of a biological membrane to the other. SCOPE OF
      REVIEW: This review aims to identify common mechanistic features in the way
      phospholipid flipping is carried out by two evolutionarily unrelated families of
      transporters. MAJOR CONCLUSIONS: Both protein families hydrolyze ATP, although
      they employ different mechanisms to use it, and have a comparable size with
      twelve transmembrane segments in the functional unit. Further, despite
      differences in overall architecture, both appear to operate by an alternating
      access mechanism and during transport they might allow access of phospholipids to
      the internal part of the transmembrane domain. The latter feature is obvious for
      ABC transporters, but phospholipids and other hydrophobic molecules have also
      been found embedded in P-type ATPase crystal structures. Taken together, in two
      diverse groups of pumps, nature appears to have evolved quite similar ways of
      flipping phospholipids. GENERAL SIGNIFICANCE: Our understanding of the structural
      basis for phospholipid flipping is still limited but it seems plausible that a
      general mechanism for phospholipid flipping exists in nature. This article is
      part of a Special Issue entitled Structural biochemistry and biophysics of
      membrane proteins.

PMID- 24746985
TI  - Evaluation of hepatitis delta virus (HDV) infection in blood donors in western
      Turkey.
AB  - BACKGROUND: Hepatitis B virus (HBV) and hepatitis delta virus (HDV) infections
      are potentially dangerous complications of transfusion therapy. OBJECTIVE: The
      aim of this study was to determine the prevalence of HDV markers examined by
      serological and molecular methods in hepatitis B surface antigen (HBsAg)-reactive
      sera among blood donors. MATERIALS AND METHODS: Samples from 88 HBsAg-reactive
      blood donors were investigated for total anti-delta antibody (anti-HDV) and HDV
      RNA between April 2010 and February 2011. HBsAg screening tests were performed by
      "microparticle enzyme immunoassay" (MEIA) method using the AxSYM system (Abbott
      Laboratories, USA), and total anti-delta antibody tests were performed by MEIA
      method using the Alisei system (Radim, Italy). HDV-RNA was quantified using the
      polymerase chain reaction (PCR) method. Viral nucleic acid isolation system
      (Anatolia Geneworks) was used with Bosphore HDV quantification kit. RESULTS:
      HBsAg reactivity was determined as 1% (124/12.423) among blood donors as a whole.
      Eighty-eight of these 124 samples were investigated further for HDV. Three (3.4%)
      of the 88 HBsAg-reactive serum samples were total anti-delta antibody-reactive.
      Of the 3 anti-HDV-reactive sera, 2 were reactive for HDV-RNA. Therefore, HDV-RNA
      reactivity was determined as 2.3% (2/88) in HBsAg-reactive donors as a whole. The
      2 HDV-RNA-reactive donors were brothers. CONCLUSIONS: Investigation of HDV is
      important because HBV infection is endemic in Turkey. Intrafamilial transmission
      is important in HDV transmission.

PMID- 24746986
TI  - Reply to Professor Taylor.

PMID- 24746987
TI  - Zinc oxide nanoparticles induce migration and adhesion of monocytes to
      endothelial cells and accelerate foam cell formation.
AB  - Metal oxide nanoparticles are widely used in industry, cosmetics, and
      biomedicine. However, the effects of exposure to these nanoparticles on the
      cardiovascular system remain unknown. The present study investigated the effects
      of nanosized TiO2 and ZnO particles on the migration and adhesion of monocytes,
      which are essential processes in atherosclerogenesis, using an in vitro set-up of
      human umbilical vein endothelial cells (HUVECs) and human monocytic leukemia
      cells (THP-1). We also examined the effects of exposure to nanosized metal oxide
      particles on macrophage cholesterol uptake and foam cell formation. The 16-hour
      exposure to ZnO particles increased the level of monocyte chemotactic protein-1
      (MCP-1) and induced the migration of THP-1 monocyte mediated by increased MCP-1.
      Exposure to ZnO particles also induced adhesion of THP-1 cells to HUVECs.
      Moreover, exposure to ZnO particles, but not TiO2 particles, upregulated the
      expression of membrane scavenger receptors of modified LDL and increased
      cholesterol uptake in THP-1 monocytes/macrophages. In the present study, we found
      that exposure to ZnO particles increased macrophage cholesterol uptake, which was
      mediated by an upregulation of membrane scavenger receptors of modified LDL.
      These results suggest that nanosized ZnO particles could potentially enhance
      atherosclerogenesis and accelerate foam cell formation. 

PMID- 24746989
TI  - Participation in and impact of a depression care management program targeting low
      income minority patients in an urban community-based clinic.
AB  - BACKGROUND: African American people experience disproportionately higher rates of
      chronic depression, and among those affected, the condition is less likely to be
      detected and treated than in non-Hispanic white people. OBJECTIVE: To address
      this disparity in our primary care clinic, we introduced a validated framework
      for detecting and managing depression. METHODS: Over a 5-year period, there were
      146 patients diagnosed as having depression and enrolled in a depression care
      management program. We evaluated the feasibility and effectiveness of that
      program using baseline and follow-up screening data from the Patient Health
      Questionnaire-9. RESULTS: The mean baseline severity score of 20.60 was reduced
      to 15.89 at 6 months (P < 0.001) and to 16.62 at 12 months. Patients achieved
      their best score, a mean of 12.93, 10.14 months after baseline (P < 0.001). The
      last mean severity score, after 15.47 months, was 14.60, a significant difference
      compared with baseline (P < 0.001). Although baseline severity scores for both
      groups were similar (P = 0.534), patients who remained engaged with the program
      demonstrated better scores and achieved greater severity score reductions from
      baseline to the last measure (P < 0.001). This study did not find any differences
      between the sexes when comparing PHQ-9 scores at baseline (P = 0.074), 6 months
      (P = 0.303), and 12 months (P = 0.429) and best (P = 0.875) and last (P = 0.640)
      scores. CONCLUSIONS: Most of the improvement was witnessed in the first 10 months
      of treatment. Patients with more medical comorbidities participated longer in the
      study than patients with fewer comorbidities. Further research could elicit the
      relationship between improvement in mental health and medical conditions.

PMID- 24746988
TI  - Exploring the potential role of tungsten carbide cobalt (WC-Co) nanoparticle
      internalization in observed toxicity toward lung epithelial cells in vitro.
AB  - Tungsten carbide cobalt (WC-Co) has been recognized as a workplace inhalation
      hazard in the manufacturing, mining and drilling industries by the National
      Institute of Occupational Safety and Health. Exposure to WC-Co is known to cause
      "hard metal lung disease" but the relationship between exposure, toxicity and
      development of disease remain poorly understood. To better understand this
      relationship, the present study examined the role of WC-Co particle size and
      internalization on toxicity using lung epithelial cells. We demonstrated that
      nano- and micro-WC-Co particles exerted toxicity in a dose- and time-dependent
      manner and that nano-WC-Co particles caused significantly greater toxicity at
      lower concentrations and shorter exposure times compared to micro-WC-Co
      particles. WC-Co particles in the nano-size range (not micron-sized) were
      internalized by lung epithelial cells, which suggested that internalization may
      play a key role in the enhanced toxicity of nano-WC-Co particles over micro-WC-Co
      particles. Further exploration of the internalization process indicated that
      there may be multiple mechanisms involved in WC-Co internalization such as actin
      and microtubule based cytoskeletal rearrangements. These findings support our
      hypothesis that WC-Co particle internalization contributes to cellular toxicity
      and suggest that therapeutic treatments inhibiting particle internalization may
      serve as prophylactic approaches for those at risk of WC-Co particle exposure. 

PMID- 24746990
TI  - Pneumococcal vaccination in Europe: schedule adherence.
AB  - Nonadherence to recommended pneumococcal conjugate vaccine (PCV) schedules may
      have implications for protection against pneumococcal disease. In this
      commentary, we have assessed adherence to the recommended dosing schedules (the
      completion of the primary PCV and booster series) in different European
      countries. We found that adherence with the PCV schedule was lower than that for
      diphtheria-tetanus-acellular pertussis (DTaP) and that higher adherence was
      observed in countries where PCV vaccination is recommended and funded. Adherence
      with the booster dose is often lower than that with the primary series
      completion, and it is often given after the recommended age. These data highlight
      the need to encourage timely vaccination of children with PCV, in line with local
      immunization schedules. There is no single solution to improve adherence; actions
      need to be tailored to the context of individual countries through initiatives at
      the national, regional, and local levels and should target different
      stakeholders.

PMID- 24746991
TI  - Continuous renal replacement therapy and mild hypothermia for acute left heart
      failure after cardiovascular surgery.

PMID- 24746992
TI  - Intraoperative pulmonary flow study for decision making in the comprehensive
      stage II hybrid procedure.

PMID- 24746993
TI  - Nationwide survey of US integrated 6-year cardiothoracic surgical residents.
AB  - OBJECTIVE: Integrated 6-year cardiothoracic surgical residency programs have
      recently been implemented in the United States. We report the results of the
      first published nationwide survey assessing the motivations, satisfaction, and
      ambitions of integrated 6-year residents. METHODS: A 63-question web-based survey
      was distributed to 83 residents enrolled in 21 Accreditation Council for Graduate
      Medical Education-accredited integrated 6-year programs in November 2013. There
      was an outstanding 69% response rate. RESULTS: The median age of integrated 6
      year residents was 29 years with women comprising 24%. A clear majority had
      faculty mentorship (95%) and significant clinical exposure in medical school.
      Focused (100%) and abbreviated (74%) training curricula were identified as the
      top advantages of integrated 6-year programs; the format itself was a significant
      factor (46%) in career choice. Most integrated 6-year residents (95%) were
      satisfied with their program; 80.7% were satisfied with their operative
      experience thus far. Career plans skewed toward adult cardiac surgery (67%),
      followed by pediatric cardiac (24%) and general thoracic (9%) surgery; 49% were
      not particularly concerned about future employment, with 65% foreseeing an
      increase in opportunities. Specialized training (eg, aortic, heart failure,
      minimally invasive, congenital) was anticipated by 77%. Most integrated 6-year
      residents envision an academic career (94.7%). CONCLUSIONS: This survey takes an
      important snapshot of the nascent integrated 6-year format. Mentorship and
      intense clinical exposure are critical in attracting applicants. Purported
      advantages of the format are holding true among integrated 6-year residents, with
      the majority satisfied with their programs. These early data indicate that this
      format holds significant promise in attracting and retaining highly qualified
      trainees to academic cardiothoracic surgery.

PMID- 24746995
TI  - Outcomes and efficacy of thoracic surgery biopsy for tumor molecular profiling in
      patients with advanced lung cancer.
AB  - BACKGROUND: Molecular testing of patients with advanced non-small cell lung
      cancer for personalized therapy often is limited by insufficient specimen from
      nonsurgical biopsies. We measured the feasibility, patient safety, and clinical
      impact of thoracic surgical tumor biopsy in patients with stage IV non-small cell
      lung cancer. METHODS: This is a single institution retrospective analysis.
      Patients with stage IV non-small cell lung cancer undergoing elective surgical
      tissue biopsy for molecular analysis were evaluated from March 2011 to November
      2012. Perioperative specific variables were measured. RESULTS: Twenty-five
      patients with known or suspected stage IV non-small cell lung cancer undergoing
      surgical biopsy were identified. All cases were discussed at a multidisciplinary
      thoracic oncology conference or a multidisciplinary thoracic oncology clinic.
      Preoperative histologies included adenocarcinoma in 20 patients (80.0%) and
      squamous cell carcinoma in 2 patients (8.0%). Surgical procedures consisted of
      video-assisted thoracic surgery wedge biopsy (16, 64%), video-assisted thoracic
      surgery pleural biopsy (4, 16.0%), mediastinoscopy (2, 8.0%),
      supraclavicular/cervical lymph node excisional biopsy (3, 12.0%), and rib/chest
      wall resection (2, 8.0%). There were no deaths and 5 postoperative complications
      (20.0%). Surgery identified potentially targetable molecular information in 19 of
      the total patients undergoing operation (76.0%) and changed the treatment
      strategy in 14 patients (56.0%); 10 of the total cohort (40.0%) were enrolled
      into therapeutic targeted clinical trials. CONCLUSIONS: These data suggest that
      thoracic surgical biopsy can be safely performed in appropriately selected
      patients with stage IV non-small cell lung cancer and direct personalized therapy
      and enrollment into relevant clinical trials. Patients with advanced-stage non
      small cell lung cancer should be discussed in a multidisciplinary setting to
      determine the need and strategy for thoracic surgical biopsy for molecular
      analysis.

PMID- 24746994
TI  - Clinical outcomes and changes in lung function after segmentectomy versus
      lobectomy for lung cancer cases.
AB  - OBJECTIVE: We compared the clinical outcomes and changes in pulmonary function
      test (PFT) results after segmentectomy or lobectomy for non-small cell lung
      cancer. METHODS: The retrospective study included 212 patients who had undergone
      segmentectomy (group S) and 2336 patients who had undergone lobectomy (group L)
      from 1997 to 2012. The follow-up and medical record data were collected. We used
      all the longitudinal PFT data within 24 months postoperatively and performed
      linear mixed modeling. We analyzed the 5-year overall and disease-free survival
      in stage IA patients. We used propensity score case matching to minimize the bias
      due to imbalanced group comparisons. RESULTS: During the perioperative period, 1
      death (0.4%) in group S and 7 (0.3%) in group L occurred. The hospital stay for
      the 2 groups was similar (median, 5.0 vs 5.0 days; range, 2-99 vs 2-58). The mean
      overall and disease-free survival period of those with T1a after segmentectomy or
      lobectomy seemed to be similar (4.2 vs 4.5 years, P=.06; and 4.1 vs 4.4 years,
      P=.07, respectively). Compared with segmentectomy, lobectomy yielded marginally
      significantly better overall (4.4 vs 3.9 years, P=.05) and disease-free (4.1 vs
      3.6 years; P=.05) survival in those with T1b. We did not find a significantly
      different effect on the PFTs after segmentectomy or lobectomy. CONCLUSIONS: Both
      surgical types were safe. We would advocate lobectomy for patients with stage IA
      disease, especially those with T1b. A retrospective study with a large sample
      size and more detailed information should be conducted for PFT evaluation, with
      additional stratification by lobe and laterality.

PMID- 24746996
TI  - Giant aneurysm of a major aortopulmonary collateral artery in a 56-year-old
      woman.

PMID- 24746997
TI  - Prediction of preeclampsia utilizing the first trimester screening examination.
AB  - OBJECTIVE: To derive a prediction rule for preeclampsia and early onset
      preeclampsia requiring delivery <34 weeks using first trimester maternal,
      ultrasound, and serum markers. STUDY DESIGN: Prospective cohort study of women
      enrolled at first trimester screening. Maternal history, demographics,
      anthropometry, ultrasound parameters, and serum analytes were compared between
      women with preeclampsia and normal outcome. The prediction rule was derived by
      Lasso logistic regression analysis. RESULTS: In 2441 women, 108 (4.4%) women
      developed preeclampsia, and 18 (0.7%) early preeclampsia. Nulliparity, prior
      hypertension, diabetes, prior preeclampsia, mean arterial pressure, and the log
      pregnancy-associate pregnancy protein-A multiples of the median were primary risk
      factors. Prediction rules for preeclampsia/early preeclampsia had an area under
      the curve of 0.82/0.83 respectively. Preeclampsia was predicted with 49%
      sensitivity and early preeclampsia with 55% sensitivity for a 10% false positive
      rate. CONCLUSION: First trimester prediction rules using parameters currently
      available at first trimester screening identify a significant proportion of women
      with subsequent preeclampsia.

PMID- 24746998
TI  - Benefit of interpregnancy HIV viral load suppression on subsequent maternal and
      infant outcomes.
AB  - OBJECTIVE: The objective of the study was to determine whether interpregnancy
      human immunodeficiency virus (HIV) viral load suppression affects outcomes in
      subsequent pregnancies. STUDY DESIGN: This is a retrospective review of all women
      who delivered 2 consecutive pregnancies while diagnosed with HIV from Jan. 1,
      1984, until Jan. 1, 2012. Medical records were reviewed for maternal, infant, and
      delivery data. Pregnancies were divided into index and subsequent pregnancy and
      analyzed for outcomes. RESULTS: During the study period, 172 HIV-infected women
      who delivered 2 pregnancies at our institution were identified. There was no
      difference in median HIV viral load at presentation or delivery between the index
      and subsequent pregnancies. During the subsequent pregnancy, more women presented
      on antiretroviral therapy (ART) and more often remained compliant with ART;
      however, there was no difference in vertical transmission risk between the
      pregnancies. Of those with a viral load less than 1000 copies/mL at the end of
      their index pregnancy (n = 103), 57 (55%) presented for their subsequent
      pregnancy with a viral load still less than 1000 copies/mL. Those women who
      maintained the viral load suppression between pregnancies were more likely to
      present for their subsequent pregnancy on ART, maintained a greater viral load
      suppression and CD4 counts during the pregnancy, and had fewer vertical
      transmissions compared with those who presented with higher viral loads in their
      subsequent pregnancy (0% vs 9%, P = .02). CONCLUSION: Maintaining an HIV viral
      load suppression between pregnancies is associated with improved HIV disease
      status at delivery in subsequent pregnancies. Interpregnancy HIV viral load
      suppression is associated with less vertical transmission, emphasizing the
      importance of maintaining HIV disease control between pregnancies.

PMID- 24746999
TI  - Balancing the risks of stillbirth and neonatal death in the early preterm small
      for-gestational-age fetus.
AB  - OBJECTIVE: Timing of delivery for the early preterm small-for-gestational-age
      (SGA) fetus remains unknown. Our aim was to estimate the risk of stillbirth in
      the early preterm SGA fetus compared with the risk of neonatal death. STUDY
      DESIGN: We performed a retrospective cohort study of singleton pregnancies that
      underwent second-trimester anatomy ultrasound (excluding fetal anomalies,
      aneuploidy, and pregnancies with incomplete neonatal follow-up data). SGA was
      defined as birthweight <10th percentile by the Alexander standard. Life-table
      analysis was used to calculate the cumulative risks of stillbirth per 10,000
      ongoing SGA pregnancies and of neonatal death per 10,000 SGA live births for 2
      week gestational age strata in the early preterm period (24-33 weeks 6 days of
      gestation). We further examined the composite risk of expectant management and
      then compared the risk of expectant management with the risk of immediate
      delivery. RESULTS: Of 76,453 singleton pregnancies, 7036 SGA pregnancies that met
      inclusion criteria were ongoing at 24 weeks of gestation; there were 64
      stillbirths, 226 live births, and 18 neonatal deaths from 24-33 weeks 6 days of
      gestation. As the risk of stillbirth increases with advancing gestational age,
      the risk of neonatal death falls, until the 32-33 weeks 6 days of gestation
      stratum. The relative risk of expectant management compared with immediate
      delivery remains <1 for each gestational age strata. CONCLUSION: Our findings
      suggest that the balance between the competing risks of stillbirth and neonatal
      death for the early preterm SGA fetus occurs at 32-33 weeks 6 days of gestation.
      These data can be useful when delivery timing remains uncertain.

PMID- 24747000
TI  - Neural mechanisms of motivated forgetting.
AB  - Not all memories are equally welcome in awareness. People limit the time they
      spend thinking about unpleasant experiences, a process that begins during
      encoding, but that continues when cues later remind someone of the memory. Here,
      we review the emerging behavioural and neuroimaging evidence that suppressing
      awareness of an unwelcome memory, at encoding or retrieval, is achieved by
      inhibitory control processes mediated by the lateral prefrontal cortex. These
      mechanisms interact with neural structures that represent experiences in memory,
      disrupting traces that support retention. Thus, mechanisms engaged to regulate
      momentary awareness introduce lasting biases in which experiences remain
      accessible. We argue that theories of forgetting that neglect the motivated
      control of awareness omit a powerful force shaping the retention of our past. 

PMID- 24747001
TI  - Elevated PDGFRB gene copy number gain is prognostic for improved survival
      outcomes in resected malignant pleural mesothelioma.
AB  - PDGF/PDGFR pathway has been implicated in malignant pleural mesothelioma (MPM)
      carcinogenesis, and evidence suggests autocrine mechanisms of proliferation. We
      sought to evaluate the incidence of PDGFRB gene copy number gain (CNG) by
      fluorescence in situ hybridization and PDGFR pathway protein expression by
      immunohistochemistry (IHC) and correlate it to patient clinical outcome. Eighty
      eight archived tumor blocks from resected MPM with full clinical information were
      used to perform IHC biomarkers (PDGFRalpha, PDGFRbeta, p-PDGFRbeta) and
      fluorescence in situ hybridization analysis of PDGFRB gene CNG. Spearman rank
      correlation, Wilcoxon rank-sum test, Kruskal-Wallis test, BLiP plots, and Kaplan
      Meier method were used to analyze the biomarkers and correlation to clinical
      outcome. Several correlations between the IHC biomarkers were seen; however, none
      correlated to clinically relevant patient demographics or histology. In the CNG
      analysis, PDGFRB gene CNG in >10% of tumor cells had lower cytoplasmic p
      PDGFRbeta (P=.029), while PDGFRB gene CNG in >40% of tumor cells had a higher
      cytoplasmic PDGFRbeta (P=.04). PDGFRB gene CNG status did not associate with
      patient demographics or tumor characteristics. PDGFR pathway IHC biomarkers did
      not associate with survival outcomes. However, patients with PDGFRB CNG >40% of
      tumor cells had improved relapse-free survival (HR 0.25 [95% CI 0.09-0.72],
      P=.0096) and improved overall survival (HR 0.32 [95% CI 0.11-0.89], P=.029).
      PDGFRB CNG >40% of MPM tumor cells is a potential prognostic biomarker for
      surgery and may identify a unique population of mesothelioma patients. Future
      validation of this biomarker in prospective trials is needed. From a
      retrospective review of archived tissue specimens from patients with resected
      malignant pleural mesothelioma tumors, we show that patients with PDGFRB CNG >40%
      of tumor cells had improved relapse-free survival (HR 0.25 [95% CI 0.09-0.72],
      P=.0096) and improved overall survival (HR 0.32 [95% CI 0.11-0.89], P=.029).
      PDGFRB CNG >40% of MPM tumor cells is a potential prognostic biomarker for
      surgery and may identify a unique population of mesothelioma patients. 

PMID- 24747002
TI  - Codon-based phylogenetics introduces novel flagellar gene markers to oomycete
      systematics.
AB  - Oomycete systematics has traditionally been reliant on ribosomal RNA and
      mitochondrial cytochrome oxidase sequences. Here we report the use of two single
      copy protein-coding flagellar genes, PF16 and OCM1, in oomycete systematics,
      showing their utility in phylogenetic reconstruction and species identification.
      Applying a recently proposed mutation-selection model of codon substitution, the
      phylogenetic relationships inferred by flagellar genes are largely in agreement
      with the current views of oomycete evolution, whereas nucleotide- and amino acid
      level models produce biologically implausible reconstructions. Interesting
      parallels exist between the phylogeny inferred from the flagellar genes and
      zoospore ontology, providing external support for the tree obtained using the
      codon model. The resolution achieved for species identification is ample using
      PF16, and quite robust using OCM1, and the described PCR primers are able to
      amplify both genes for a range of oomycete genera. Altogether, when analyzed with
      a rich codon substitution model, these flagellar genes provide useful markers for
      the oomycete molecular toolbox. 

PMID- 24747003
TI  - Molecular systematics of subtribe Orchidinae and Asian taxa of Habenariinae
      (Orchideae, Orchidaceae) based on plastid matK, rbcL and nuclear ITS.
AB  - The subtribe Orchidinae, distributed predominantly in Eastern Asia and the
      Mediterranean, presents some of the most intricate taxonomic problems in the
      family Orchidaceae with respect to generic delimitation. Based on three DNA
      markers (plastid matK, rbcL, and nuclear ITS), morphological characters, and a
      broad sampling of Orchidinae and selected Habenariinae mainly from Asia (a total
      of 153 accessions of 145 species in 31 genera), generic delimitation and
      phylogenetic relationships within the subtribe Orchidinae and Habenariinae from
      Asia were assessed. Orchidinae and Asian Habenariinae are monophyletic, and
      Orchidinae is divided into distinct superclades. Many genera, such as
      Amitostigma, Habenaria, Hemipilia, Herminium, Platanthera, Peristylus and
      Ponerorchis, are not monophyletic. Habenaria is subdivided into two distantly
      related groups, while Platanthera is subdivided into three even more disparate
      groups. Many previously undetected phylogenetic relationships, such as clades
      formed by the Amitostigma-Neottianthe-Ponerorchis complex, Platanthera latilabris
      group, Ponerorchis chrysea, Sirindhornia, and Tsaiorchis, are well supported by
      both molecular and morphological evidence. We propose to combine Hemipiliopsis
      with Hemipilia, Amitostigma and Neottianthe with Ponerorchis, Smithorchis with
      Platanthera, and Aceratorchis and Neolindleya with Galearis, and to establish a
      new genus to accommodate Ponerorchis chrysea. Tsaiorchis and Sirindhornia are two
      distinctive genera supported by both molecular data and morphological characters.
      A new genus, Hsenhsua, and 41 new combinations are proposed based on these
      findings.

PMID- 24747004
TI  - Bone mineral density of the femur in autopsy retrieved total knee arthroplasties.
AB  - Bone mineral density (BMD), as measured by DEXA, can vary depending on bone
      rotation and fat content of soft tissues. We performed DEXA measurements, under
      controlled positioning, on 24 autopsy-retrieved femora from patients who had
      fully functional and asymptomatic successful TKA to determine periprosthetic BMD
      changes and compared results to 24 normal cadaveric femora. In TKA specimens, BMD
      was affected by gender, preoperative diagnosis, and zone under analysis. The
      lowest mean BMD was in the anterior femoral condylar zone. Males had higher mean
      BMD at all zones while patients with preoperative diagnosis of osteoarthritis had
      higher BMD in the posterior condylar zone. The mean BMD in the anterior femoral
      condylar zone in TKA specimens was significantly lower than in normal specimens
      without arthroplasties, most likely due to stress shielding. 

PMID- 24747006
TI  - Assessment of cell death studies by monitoring hydrogen peroxide in cell culture.
AB  - Hydrogen peroxide (H2O2) has been widely used to study the oxidative stress
      response. However, H2O2 is unstable and easily decomposes into H2O and O2.
      Consequently, a wide range of exposure times and treatment concentrations has
      been described in the literature. In the present study, we established a ferrous
      oxidation-xylenol orange (FOX) assay, which was originally described for food and
      body liquids, as a method for the precise quantification of H2O2 concentrations
      in cell culture media. We observed that the presence of FCS and high cell
      densities significantly accelerate the decomposition of H2O2, therefore acting as
      a protection against cell death by accidental necrosis. 

PMID- 24747005
TI  - Characterization of the specificity of O-GlcNAc reactive antibodies under
      conditions of starvation and stress.
AB  - The dynamic modification of nuclear, cytoplasmic, and mitochondrial proteins by O
      linked beta-N-acetyl-D-glucosamine (O-GlcNAc) has been shown to regulate over
      3000 proteins in a manner analogous to protein phosphorylation. O-GlcNAcylation
      regulates the cellular stress response and the cell cycle, and is implicated in
      the etiology of neurodegeneration, type II diabetes, and cancer. The antibody
      CTD110.6 is often used to detect changes in the O-GlcNAc modification. Recently,
      it has been demonstrated that CTD110.6 recognizes N-linked N,N'
      diacetylchitobiose, which is thought to accumulate in cells experiencing severe
      glucose deprivation. In this study, we have addressed two questions: (1) Which
      other antibodies used to detect O-GlcNAc cross-react with N-linked N,N'
      diacetylchitobiose? (2) Does N-linked N,N'-diacetylchitobiose accumulate in
      response to other cellular stressors? To delineate between O-GlcNAc and N-linked
      N,N'-diacetylchitobiose, we developed a workflow that has been used to confirm
      the specificity of a variety of O-GlcNAc-specific antibodies. Using this workflow
      we demonstrated that heat shock, osmotic stress, endoplasmic reticulum stress,
      oxidative stress, DNA damage, proteasomal inhibition, and ATP depletion induce O
      GlcNAcylation but not N-linked N,N'-diacetylchitobiose. Moreover, we demonstrated
      that while glucose deprivation results in an induction in both O-GlcNAc and N
      linked N,N'-diacetylchitobiose, the induction of N-linked N,N'-diacetylchitobiose
      is exacerbated by the removal of fetal bovine serum.

PMID- 24747008
TI  - Development of a reverse transcription loop-mediated isothermal amplification
      assay for the rapid diagnosis of avian influenza A (H7N9) virus infection.
AB  - A genetic diagnosis system for detecting avian influenza A (H7N9) virus infection
      using reverse transcription-loop-mediated isothermal amplification (RT-LAMP)
      technology was developed. The RT-LAMP assay showed no cross-reactivity with
      seasonal influenza A (H3N2 and H1N1pdm09) or influenza B viruses circulating in
      humans or with avian influenza A (H5N1) viruses. The sensitivity of the RT-LAMP
      assay was 42.47 copies/reaction. Considering the high specificity and sensitivity
      of the assay for detecting the avian influenza A (H7N9) virus and that the
      reaction was completed within 30 min, the RT-LAMP assay developed in this study
      is a promising rapid diagnostic tool for avian influenza A (H7N9) virus
      infection.

PMID- 24747007
TI  - Long-term effects of child abuse and neglect on emotion processing in adulthood.
AB  - To determine whether child maltreatment has a long-term impact on emotion
      processing abilities in adulthood and whether IQ, psychopathology, or psychopathy
      mediate the relationship between childhood maltreatment and emotion processing in
      adulthood. Using a prospective cohort design, children (ages 0-11) with
      documented cases of abuse and neglect during 1967-1971 were matched with non
      maltreated children and followed up into adulthood. Potential mediators (IQ, Post
      Traumatic Stress [PTSD], Generalized Anxiety [GAD], Dysthymia, and Major
      Depressive [MDD] Disorders, and psychopathy) were assessed in young adulthood
      with standardized assessment techniques. In middle adulthood (Mage=47), the
      International Affective Picture System was used to measure emotion processing.
      Structural equation modeling was used to test mediation models. Individuals with
      a history of childhood maltreatment were less accurate in emotion processing
      overall and in processing positive and neutral pictures than matched controls.
      Childhood physical abuse predicted less accuracy in neutral pictures and
      childhood sexual abuse and neglect predicted less accuracy in recognizing
      positive pictures. MDD, GAD, and IQ predicted overall picture recognition
      accuracy. However, of the mediators examined, only IQ acted to mediate the
      relationship between child maltreatment and emotion processing deficits. Although
      research has focused on emotion processing in maltreated children, these new
      findings show an impact child abuse and neglect on emotion processing in middle
      adulthood. Research and interventions aimed at improving emotional processing
      deficiencies in abused and neglected children should consider the role of IQ. 

PMID- 24747009
TI  - Rapid and sequential quantitation of salivary gland-associated mouse
      cytomegalovirus in oral lavage.
AB  - Cytomegalovirus (CMV) establishes a persistent infection in the salivary glands
      and transmits to other hosts. Mouse cytomegalovirus (MCMV) is a well
      characterized model for studying the mechanisms of host responses against CMV.
      The viral load in salivary glands has been measured traditionally because it has
      been considered to reflect the consequence of anti-virus responses by T cells and
      natural killer (NK) cells. However, the standard plaque assay is cumbersome and
      it is impossible to monitor sequentially the viral load in same host. Hence, the
      goal of this study was to develop a real-time quantitative PCR (qPCR)-based
      procedure to measure the viral load in oral lavage. This report demonstrates that
      the viral load in oral lavage correlates well with viral titers in the salivary
      glands. This method allows sequential quantitation of viral loads without
      sacrificing mice and provides a technique that will facilitate kinetic studies of
      anti-viral immunity mediated by the innate and adaptive immune systems.

PMID- 24747010
TI  - Selection and characterization of single-chain recombinant antibodies against
      infectious haematopoietic necrosis virus from mouse phage display library.
AB  - Six single-chain fragment variable (scFv) antibodies against infectious
      haematopoietic necrosis virus (IHNV) were selected from an antibody phage display
      library by phage display technology. The soluble scFv antibodies showed a
      molecular weight 32kDa by Western blot. Dot blot analysis revealed that the six
      scFv antibodies could recognize IHNV. For enzyme linked immunosorbent assay
      (ELISA), four scFv antibodies (P1A4, P1A12, P1D5 and P3E2) showed cross
      reactivity with spring viraemia of carp virus (SVCV). However, none of the six
      scFv antibodies had cross-reaction with Pike fry rhabdovirus (PFRV), Soft-shelled
      turtle iridovirus (STIV), viral haemorrhagic septicemia virus (VHSV), or viral
      nervous necrosis virus (VNNV). Indirect immunofluorescence results showed that
      all of these scFv antibodies reacted positively with virus in the IHNV-infected
      cells. These scFv antibodies will be useful in diagnostic test development and
      pathogenesis studies for IHNV.

PMID- 24747011
TI  - Spinal cord injury, immunodepression, and antigenic challenge.
AB  - The inability to effectively control microbial infection is a leading cause of
      morbidity and mortality in individuals affected by spinal cord injury (SCI).
      Available evidence from clinical studies as well as animal models of SCI
      demonstrate that increased susceptibility to infection is derived from disruption
      of central nervous system (CNS) communication with the host immune system that
      ultimately leads to immunodepression. Understanding the molecular and cellular
      mechanisms governing muted cellular and humoral responses that occur post-injury
      resulting in impaired host defense following infection is critical for improving
      the overall quality of life of individuals with SCI. This review focuses on
      studies performed using preclinical animal models of SCI to evaluate how injury
      impacts T and B lymphocyte responses following either viral infection or
      antigenic challenge. 

PMID- 24747012
TI  - Identification and characterisation of a novel 1-Cys thioredoxin peroxidase gene
      (AccTpx5) from Apis cerana cerana.
AB  - Thioredoxin peroxidases (Tpxs), members of the antioxidant protein family, play
      critical roles in resisting oxidative stress. In this work, a novel 1-Cys
      thioredoxin peroxidase gene was isolated from Apis cerana cerana and was named
      AccTpx5. The open reading frame (ORF) of AccTpx5 is 663bp in length and encodes a
      220-amino acid protein with a predicted molecular mass and isoelectric point of
      24,921kDa and 5.45, respectively. Promoter sequence analysis of AccTpx5 revealed
      the presence of putative transcription factor binding sites related to early
      development and stress responses. Additionally, real-time quantitative PCR (Q
      PCR) analysis indicated that AccTpx5 was primarily present in some developmental
      stages, with the highest expression levels in the first-instar larvae. The
      expression level of AccTpx5 was up-regulated under various abiotic stresses,
      including 4 degrees C, 42 degrees C, HgCl2, H2O2, phoxim and acaricide
      treatments. Conversely, it was down-regulated by UV and pyriproxyfen treatments.
      Moreover, H2O2 concentration dramatically increased under a variety of stressful
      conditions. Finally, the purified recombinant AccTpx5 protein protected the
      supercoiled form of plasmid DNA from damage in the thiol-dependent mixed-function
      oxidation (MFO) system. These results suggest that AccTpx5 most likely plays an
      essential role in antioxidant defence. 

PMID- 24747013
TI  - Gene cloning, expression, and function analysis of SpL14-3-3zeta in Spodoptera
      litura and its response to the entomopathogenic fungus Nomuraea rileyi.
AB  - The 14-3-3 proteins, a highly evolutionarily conserved and ubiquitous protein
      family in eukaryotic cells, have a range of biological functions including
      regulation of signal transduction, stress response, apoptosis, and control of the
      cell cycle. To investigate the function of 14-3-3 in Spodoptera litura, the full
      length of 14-3-3zeta was cloned from S. litura on the basis of an expressed
      sequence tag of 14-3-3zeta from the S. litura fat body suppression subtractive
      hybridization library, and named SpL14-3-3zeta. SpL14-3-3zeta cDNA was 1196 bp
      with an open reading frame of 744 bp, encoding 247 amino acids. Multiple
      alignment analysis revealed the putative amino acids shared >80% homology with 14
      3-3zeta from other organisms and shared typical conservative structures.
      Phylogenetic analysis confirmed SpL14-3-3zeta was closely related to other
      available Lepidoptera 14-3-3zeta. Real-time PCR analysis indicated SpL14-3-3zeta
      was expressed throughout the developmental stages of S. litura, with a relatively
      high expression level in pre-pupa, and was expressed constitutively in all
      examined tissues with relatively high levels in hemocytes and midgut. Moreover,
      the transcription level of SpL14-3-3zeta could be induced by Nomuraea rileyi
      infection, up-regulated in hemocytes, followed by head, fat body and midgut.
      Knocking down SpL14-3-3zeta transcripts by RNAi significantly increased S. litura
      sensitivity to fungal infection, and resulted in higher mortality of S. litura
      during the larval development. These results provide novel insights into the 14-3
      3zeta signal regulation which may be related to host defense as well as larval
      development in S. litura.

PMID- 24747014
TI  - Should a native depth-dependent distribution of human meniscus constitutive
      components be considered in FEA-models of the knee joint?
AB  - The depth-dependent matrix composition of articular cartilage is important for
      its mechanical behavior. It is unknown whether the depth-dependent matrix
      composition of a meniscus is similarly important for its load-bearing function.
      The present objective was to determine whether it is necessary to account for the
      native distribution of matrix components in the cross-sectional plane of the
      meniscus, when studying its mechanical behavior in numerical models. To address
      this objective, measured depth-dependent distribution of matrix contents in the
      human meniscus, and fitted visco-elastic mechanical properties of the collagen
      were used as input in FEA simulations of a knee joint. The importance of
      including the depth-dependent matrix component constitution in the meniscus was
      determined by comparing simulations with an axisymmetric representation of the
      knee joint, which incorporated either the depth-dependent matrix composition or
      homogenized matrix. Depth-dependent differences in water, collagen and
      proteoglycan contents were observed, but these were not significantly different.
      The anterior region, with significantly higher collagen content, was
      statistically stiffer than the posterior region. However, depth wise, stiffness
      did not correlate to the constitution of the tissue. GAG content was
      significantly higher in the posterior than in the anterior region. Visco-elastic
      properties of meniscus collagen were fitted against tensile test data.
      Simulations show that the distribution of stresses and strains in the cartilage
      is slightly low when the meniscus contains a depth-dependent constitution, but
      this difference is only modest. Therefore, this study suggests that knee joint
      mechanics is rather insensitive to the distribution of constitutive components in
      the cross section of the meniscus, and that the depth-dependent matrix
      distribution of the meniscus is not essential to be included in axisymmetric
      computational models of the knee joint. 

PMID- 24747016
TI  - Identification of differentially expressed genes that potentially confer pest
      resistance in transgenic ChIFN-gamma tobacco.
AB  - Chicken interferon-gamma (ChIFN-gamma) is both an inhibitor of viral replication
      and a regulator of numerous immunological functions. However, since little is
      known about the mechanisms underlying the insect-resistance of transgenic ChIFN
      gamma, a transgenic ChIFN-gamma tobacco line was employed in the present study to
      explore this mechanism. A cDNA microarray (with 43,760 unigenes) was used to
      analyze the gene expression profiles of transgenic and wild-type (WT) tobacco
      leaves at two different growth stages. Compared with the WT, 1529 and 405
      expressed sequence tags were significantly up- or downregulated on days 119 and
      147, respectively. The differentially expressed genes (DEGs) are involved in
      metabolic regulation, cell division and differentiation, material synthesis and
      transport, signal transduction, and protein synthesis and degradation. Candidate
      genes that may increase cell density, thicken cell walls, promote secondary
      metabolite synthesis, and mediate plant hormone-induced resistance responses were
      used to identify the ChIFN-gamma-mediated insect-resistance mechanisms. The
      insect-resistance of transgenic ChIFN-gamma tobacco possibly involves unknown
      signaling pathways, which may directly or indirectly affect DEG expression
      mediating genes. The degree of pest resistance increased as the plants grew.
      Three genes likely to be related to jasmonic acid- or salicylic acid-dependent
      plant defense responses, including CAF 1, Cop 8/CSN, and HD, are implicated in
      the insect-resistance of the transgenic plants. The mechanism of transgenic ChIFN
      gamma tobacco resistance also involves RPS20 and other genes that induce microRNA
      based gene regulation. The ChIFN-gamma-mediated DGEs contribute to insect
      resistance in transgenic ChIFN-gamma tobacco, which provides new insight into the
      role of ChIFN-gamma. 

PMID- 24747015
TI  - A conserved RNA polymerase III promoter required for gammaherpesvirus TMER
      transcription and microRNA processing.
AB  - Canonical RNA polymerase III (pol III) type 2 promoters contain a single A and B
      box and are well documented for their role in tRNA and SINE transcription in
      eukaryotic cells. The genome of Murid herpesvirus 4 (MuHV-4) contains eight
      polycistronic tRNA-microRNA encoded RNA (TMER) genes that are transcribed from a
      RNA pol III type 2-like promoter containing triplicated A box elements. Here, we
      demonstrate that the triplicated A box sequences are required in their entirety
      to produce functional MuHV-4 miRNAs. We also identify that these RNA pol III type
      2-like promoters are conserved in eukaryotic genomes. Human and mouse predicted
      tRNA genes containing these promoters also show enrichment of alternative RNA pol
      III transcription termination sequences and are predicted to give rise to longer
      tRNA primary transcripts. 

PMID- 24747017
TI  - Molecular characterization and function analysis of SlNAC2 in Suaeda
      liaotungensis K.
AB  - The plant-specific NAC (NAM, ATAF1/2, and CUC) transcription factors have diverse
      roles in plant development and stress responses. In this study, a stress
      responsive NAC gene, SlNAC2, was isolated and characterized from high-throughput
      Solexa sequencing of Suaeda liaotungensis. SlNAC2 showed high similarity to other
      NACs, especially ATAF subgroup members. Transcripts of SlNAC2 appeared in many
      Suaeda tissues including leaves, stems and roots. In particular, SlNAC2 was
      strongly expressed in leaves. Expression analysis showed that SlNAC2 was highly
      induced during salt and low temperature stress in leaves. Subcellular
      localization showed that the SlNAC2 protein localized to the nucleus. A
      transactivation assay in yeast demonstrated that SlNAC2 activated the expression
      of a reporter gene. To test its function, SlNAC2 was transformed into Arabidopsis
      under the control of the CaMV-35S promoter. Functional analysis showed that its
      overexpression resulted in enhanced tolerance to salinity stress. Therefore,
      SlNAC2 is a multifunctional regulatory factor in plants, and might be a good
      candidate gene for genetic improvement to produce stress tolerant plants.

PMID- 24747019
TI  - HIV and schistosomiasis co-infection in African children.
AB  - HIV/AIDS and schistosomiasis both cause a substantial disease burden in sub
      Saharan Africa and the two diseases often overlap in their epidemiological
      characteristics. Although disease-specific control interventions are continuing,
      potential synergies in the control efforts for these two diseases have not been
      investigated. With a focus on children with schistosomiasis, we assess the risk
      for increased HIV transmission, HIV progression, and impaired response to drugs
      when given alongside HIV interventions. A new research agenda tailored to
      children is needed to better understand the interactions of these two diseases
      and the potential for combined responses. 

PMID- 24747018
TI  - The role of choroid plexus in IVIG-induced beta-amyloid clearance.
AB  - We have shown that intravenous immunoglobulin (IVIG) contains anti-Abeta
      autoantibodies and IVIG could induce beta amyloid (Abeta) efflux from
      cerebrospinal fluid (CSF) to blood in both Multiple Sclerosis (MS) and Alzheimer
      disease (AD) patients. However, the molecular mechanism underlying IVIG-induced
      Abeta efflux remains unclear. In this study, we used amyloid precursor protein
      (AbetaPP) transgenic mice to investigate if the IVIG could induce efflux of Abeta
      from the brain and whether low-density lipoprotein receptor-related protein-1
      (LRP1), a hypothetic Abeta transporter in blood-CSF barrier (BCB); could mediate
      this clearance process. We currently provide strong evidence to demonstrate that
      IVIG could reduce brain Abeta levels by pulling Abeta into the blood system in
      AbetaPP transgenic mice. In the mechanistic study, IVIG could induce Abeta efflux
      through the in vitro BCB membrane formed by cultured BCB epithelial cells. Both
      receptor-associated protein (RAP; a functional inhibitor of LRP1), and LRP1 siRNA
      were able to significantly inhibit the Abeta efflux. Should Abeta prove to be the
      underlying cause of AD, our results strongly suggest that IVIG could be
      beneficial in the therapy for AD by inducing efflux of Abeta from the brain
      through the LRP1 in the BCB.

PMID- 24747020
TI  - An adaptation study of internal and external features in facial representations.
AB  - Prior work suggests that internal features contribute more than external features
      to face processing. Whether this asymmetry is also true of the mental
      representations of faces is not known. We used face adaptation to determine
      whether the internal and external features of faces contribute differently to the
      representation of facial identity, whether this was affected by familiarity, and
      whether the results differed if the features were presented in isolation or as
      part of a whole face. In a first experiment, subjects performed a study of
      identity adaptation for famous and novel faces, in which the adapting stimuli
      were whole faces, the internal features alone, or the external features alone. In
      a second experiment, the same faces were used, but the adapting internal and
      external features were superimposed on whole faces that were ambiguous to
      identity. The first experiment showed larger aftereffects for unfamiliar faces,
      and greater aftereffects from internal than from external features, and the
      latter was true for both familiar and unfamiliar faces. When internal and
      external features were presented in a whole-face context in the second
      experiment, aftereffects from either internal or external features was less than
      that from the whole face, and did not differ from each other. While we reproduce
      the greater importance of internal features when presented in isolation, we find
      this is equally true for familiar and unfamiliar faces. The dominant influence of
      internal features is reduced when integrated into a whole-face context,
      suggesting another facet of expert face processing. 

PMID- 24747021
TI  - Key issues for the prosperity of modelling research of language evolution: Reply
      to comments on "Modelling language evolution: Examples and predictions".

PMID- 24747022
TI  - Physics and biology, two good partners: Comment on "Physical methods for genetic
      transformation of fungi and yeast" by Ana Leonor Rivera, Denis Magana-Ortiz,
      Miguel Gomez-Lim, Francisco Fernandez, Achim M. Loske.

PMID- 24747023
TI  - Label-free measurement of histone lysine methyltransferases activity by matrix
      assisted laser desorption/ionization time-of-flight mass spectrometry.
AB  - Histone lysine methyltransferases (HKMTs) are enzymes that play an essential role
      in epigenetic regulation. Thus, identification of inhibitors specifically
      targeting these enzymes represents a challenge for the development of new
      antitumor therapeutics. Several methods for measuring HKMT activity are already
      available. Most of them use indirect measurement of the enzymatic reaction
      through radioactive labeling or antibody-recognized products or coupled enzymatic
      assays. Mass spectrometry (MS) represents an interesting alternative approach
      because it allows direct detection and quantification of enzymatic reactions and
      can be used to determine kinetics and to screen small molecules as potential
      inhibitors. Application of mass spectrometry to the study of HKMTs has not been
      fully explored yet. We describe here the development of a simple reliable label
      free MALDI-TOF MS-based assay for the detection and quantification of peptide
      methylation, using SET7/9 as a model enzyme. Importantly, the use of expensive
      internal standard often required in mass spectrometry quantitative analysis is
      not necessary in this assay. This MS assay allowed us to determine enzyme kinetic
      parameters as well as IC50 for a known inhibitor of this enzyme. Furthermore, a
      comparative study with an antibody-based immunosorbent assay showed that the MS
      assay is more reliable and suitable for the screening of inhibitors. 

PMID- 24747024
TI  - [Pulmonary Langerhans' cell histiocytosis in adults: an unknown old disease].

PMID- 24747025
TI  - [Tuberculosis screening program for undocumented immigrant teenagers using the
      QuantiFERON((r))-TB Gold In-Tube test].
AB  - BACKGROUND AND OBJECTIVE: The aim of this study was to determine the prevalence
      of tuberculosis infection in undocumented immigrant teenagers using a tuberculin
      skin test (TST) for initial screening and QuantiFERON((r))-TB Gold In-Tube (QFT
      GIT) as a confirmatory test. PATIENT AND METHOD: From 2007 to 2012, under 19 year
      old immigrant teenagers from 2 accommodation centers of the Basque Country
      (Spain) were included in the study. The TST was done in all of them and the QFT
      GIT was done in selected patients with a TST>=5mm. RESULTS: Eight hundred and
      forty-five immigrants were included, most of them from Africa (99.5%). Fifty-one
      percent of immigrants with TST >= 5 mm has a positive QFT-GIT. We found 2 cases
      of active tuberculosis (2/845: 0.24%). The concordance between TST (>= 10 mm) and
      QFT-GIT was 63%, with 57% of positive concordance cases and 96% of negative
      concordances. There were 246 cases with TST >= 10 mm (29%), with significant
      differences between Magrebis (21.5%) and Subsaharians (67%) (P<.001). Vaccination
      with Calmette-Guein bacille was an independent predictor for having a TST >= 10
      mm (OR: 2.11; P<.001) and for the discordance TST+/QFT-GIT-, both for a TST>=5
      and a TST>=10mm (OR 2.16, 95% confidence interval [95% CI] 1.46-3.20, and OR 1.91
      95% CI 1.23-2.97, respectively). The positive value of QFT-GIT increased
      significantly as the TST increased, with a positive association in all the cut
      off points analyzed: 10-14 mm (OR 7.95, 95% CI 1.79-35.33), 15-19 mm (OR 35, 95%
      CI 7.93-154.52) and >= 20 mm (OR 91.3, 95% CI 18.20-458.11). CONCLUSION: Due to
      the high prevalence of latent tuberculosis infection in Subsaharian immigrants,
      we recommend implementing screening programs in this population. Using QFT-GIT,
      the number of candidates for chemoprophylaxis was reduced to 43% compared with
      TST alone (>= 10 mm).

PMID- 24747026
TI  - [Temporal evolution of treatment of patients with atrial fibrillation in a urban
      health care area].
AB  - BACKGROUND AND OBJECTIVE: To evaluate the adequacy of atrial fibrillation (AF)
      management 6 years after the establishment of a coordinated AF Unit. PATIENTS AND
      METHODS: Patients with AF attended during 14 consecutive days in the Emergency
      Room, Internal Medicine, Neurology and Arrhythmia departments of a tertiary
      hospital, and 3 primary health care centers of the same urban health care area
      were included. Treatment for AF and its adequacy to current clinical guidelines,
      tests performed and knowledge about the arrhythmia were evaluated. Results were
      compared with a population of 239 patients treated 6 years earlier. RESULTS: One
      hundred and sixty-eight patients were included. Knowledge of the arrhythmia
      improved. The adequacy of treatment (rate control, rhythm control and
      antithrombotic prophylaxis) remained at the same level as in the previous period
      in all areas. The adequacy of thromboprophylaxis was negatively associated with
      advanced age (P < .001) and positively associated with knowledge of arrhythmia (P
      = .026). CONCLUSION: Treatment of AF in a coordinated health area remains
      appropriate 6 years after the establishment of a coordinated AF unit. Elderly
      patients are still poorly anticoagulated. Health education may improve this
      deficit.

PMID- 24747027
TI  - Cardiovascular protective effects of Casearia sylvestris Swartz in Swiss and
      C57BL/6 LDLr-null mice undergoing high fat diet.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Although Casearia sylvestris Swartz is used in
      Brazilian folk medicine to treat obesity, no study has been conducted to evaluate
      the effects of this species in an experimental model of dyslipidemia and
      atherosclerosis. So, the aim of this study was to evaluate possible hypolipemiant
      and antiatherogenic activity of the methanolic extract obtained from Casearia
      sylvestris (MECS) using Swiss and C57BL/6 LDLr-null mice undergoing high fat diet
      (HFD). MATERIAL AND METHODS: Dyslipidemia and atherogenesis were induced by the
      administration of commercial HFD for 4 weeks. The MECS was administered orally at
      doses of 250 and 500mg/kg, once a day, for two weeks, starting from the 2nd week
      of HFD. The gain in body weight and systolic blood pressure (SBP) were measured
      weekly over the four week study. At the end of the experiments the levels of
      triglyceride (TG), total cholesterol (TC), high-density lipoprotein cholesterol
      (HDL-C), low-density lipoprotein cholesterol (LDL-C) and very low-density
      lipoprotein cholesterol (VLDL-C) were measured by colorimetric method.
      Aldosterone, vasopressin and angiotensin converting enzyme (ACE) activity were
      also evaluated in collected serum. The renal function, atherogenic index serum
      (AIS) and in vitro antiplatelet activity were investigated. Additionally,
      histopathological analyzes were performed to determine the intima-media thickness
      (IMT) and intima media ratio (IMR) in aorta samples. RESULTS: The HFD induced
      dyslipidemia and major structural changes in the aortic wall, including raising
      of the systolic blood pressure in LDLr-null mice. In addition, we observed an
      increase in lipid peroxidation accompanied by a reduction of serum nitrite. The
      treatment with MECS was able to prevent the increase of SBP, TC, LDL-C, VLDL-C
      and triglycerides levels and increase HDL-C in Swiss and LDLr-null mice. These
      effects were accompanied by a significant reduction in oxidative stress.
      Moreover, AIS, IMT and IMR were significantly reduced in MECS-treated mice, and
      the extract was able to reduce platelet aggregation in vitro. CONCLUSION: This
      study demonstrated that MECS reduces the serum lipids and oxidative stress when
      orally administered to Swiss and LDLr-null mice. In addition, it was able to
      prevent arterial thickening induced by HFD and to inhibit platelet aggregation in
      vitro.

PMID- 24747028
TI  - Characterisation of polyphenolic compounds in Clerodendrum petasites S. Moore and
      their potential for topical delivery through the skin.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Clerodendrum petasites S. Moore (CP) has been
      widely prescribed in Thailand and neighbouring countries for both oral and
      topical administration to treat asthma, fever, cough, vomiting and skin diseases,
      for at least 30 years. However, the nature of the active species remains poorly
      characterized and there have been no clinical trials concerning the topical
      delivery of this medicine. The study aims to characterise polyphenolic compounds
      in the plant, to predict the feasibility of their topical absorption and to test
      their ability to penetrate the skin. MATERIALS AND METHODS: Identification and
      quantification of flavonoids and phenolic acid derivatives in an ethanolic
      extract of the aerial parts of the plant were carried out using high performance
      liquid chromatography (HPLC) with photodiode array (PDA) and mass spectrometry
      (MS) detection. Ambiguous isomeric compounds were distinguished by nuclear
      magnetic resonance (NMR) spectroscopy. The feasibility of the compounds' topical
      permeability was evaluated by predicting their maximum fluxes from their
      physicochemical properties. The skin penetration of compounds in the plant
      extract was measured in vitro over 24h. RESULTS: Vanillic acid, verbascoside, 4
      coumaric acid, ferulic acid, nepetin, luteolin, apigenin, naringenin, hispidulin,
      hesperetin and chrysin, were identified in CP. All compounds except apigenin and
      hispidulin are reported in this species for the first time. Hispidulin is the
      predominant compound (1.2% w/w in a dried ethanolic extract) followed by nepetin,
      verbascoside, vanillic acid, and apigenin. Across mammalian skin, hispidulin was
      percutaneously absorbed within 3h and vanillic acid and nepetin permeated the
      skin after 6h. These experimental observations were consistent with the predicted
      maximum fluxes of these compounds calculated from their physicochemical
      properties. CONCLUSIONS: Many of the phenolic compounds reported in this study
      are well-known to possess antimicrobial, anti-inflammatory and anti-oxidant
      activities. The skin permeation studies reported here support traditional topical
      uses of the plant in skin treatments and are useful for further topical
      formulation optimisation.

PMID- 24747029
TI  - One-month toxicokinetic study of SHENMAI injection in rats.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: 'SHENMAI' injection (SMI) has been widely used in
      cardioprotection and modulation of the immune system because of its great
      efficacy. SMI primarily comprises the saponins from Panax ginseng and Ophiopogon
      japonicas. The profiles of saponins in SMI during long-term toxicokinetics remain
      unclear. MiR-146a possesses excellent sensitivity as a bio-marker in the innate
      immunity modification effect of SMI. AIM OF THE STUDY: Is to monitor the exposure
      level of SMI during a one-month toxicokinetic experiment, an analytical method
      involving ESI-LC-MS/MS technology was developed to determine 20 (S)
      protopanaxadiol-type ginsenoside (Rb1, Rb2, Rc, Rd), 20 (S)-protopanaxatriol-type
      ginsenoside (Rg1, Re, Rf), oleanolic acid-type ginsenoside (Ro), and ophiopogonin
      D in rats. The levels of AST, CK, ALT, SOD, GSH-pX, MDA, miR-146a, and ECG were
      measured to explore the effects of SMI in cardiologic function and immune
      activity. RESULTS: Results show that the levels of AST, CK, and MDA decreased
      upon the administration of SMI. The level of miR-146a increased upon the
      administration of SMI dosage. During the administration of SMI, increasing
      exposure levels of 20 (S)-protopanaxadiol-type ginsenosides were also observed.
      CONCLUSION: The 20 (S)-protopanaxadiol-type ginsenosides were considered
      potential PK/TK markers because of their high exposure levels that continuously
      increased. Oxidative stress was slightly alleviated during the toxicokinetic
      study. Based on the level of miR-146a, negatively regulated innate immunity was
      observed. The regulation became more serious with increasing exposure levels of
      20 (S)-protopanaxadiol-type ginsenosides. Negatively regulated innate immunity
      could be induced by long-term administration of SMI (>0.4g/kg).

PMID- 24747030
TI  - Prevention of UV radiation-induced cutaneous photoaging in mice by topical
      administration of patchouli oil.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Pogostemon cablin has been widely used in
      traditional Chinese medicine for the treatment of many diseases, including skin
      disorders. In the skin beauty and care prescriptions, Pogostemon cablin is one of
      the top ten frequently used traditional Chinese medicines. AIM OF THE STUDY: The
      present study was aimed to investigate the protective effects of the essential
      oil of Pogostemon cablin (patchouli oil, PO) against UV-induced skin photoaging
      in mice. MATERIALS AND METHODS: To ensure the quality of PO, the chemical
      compositions of PO were identified, and the content of its chemical marker
      patchouli alcohol was determined, which was around 28.2% (g/g) in PO. During the
      experiment period, the dorsal depilated skin of mice was treated with PO for two
      hours prior to UV irradiation. Then the protective effects of PO on UV-induced
      skin photoaging were determined by macroscopic and histological evaluations, skin
      elastic test, collagen content determination and biochemical assays of
      malondiaidehyde (MDA) content, activities of anti-oxidative indicators including
      superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT).
      RESULTS: Compared to UV exposure groups, present results showed that topical
      administration of PO, especially at dose of 6mg/mouse and 9mg/mouse,
      significantly inhibited the increase in skin wrinkle formation, alleviated the
      reduction in skin elasticity and increased the collagen content by about 21.9%
      and 26.3%, respectively. We also found that application of 6-9mg/mouse PO could
      not only decrease the epidermal thickness by about 32.6%, but also prevent the UV
      induced disruption of collagen fibers and elastic fibers. Furthermore, the
      content of MDA was decreased by almost 26.5% and activities of SOD, GSH-Px and
      CAT were significantly up-regulated after the treatment of PO. CONCLUSION:
      Results of present study revealed that PO was capable of maintaining skin
      structural integrity caused by UV irradiation and it was useful in preventing
      photoaging. These protective effects of PO were possibly due to its anti
      oxidative property. Therefore, we suggested that PO should be viewed as a
      potential therapeutic agent for preventing photoaging.

PMID- 24747031
TI  - Estimation of life expectancy and quality-adjusted life expectancy in non
      metastatic nasopharyngeal cancer patients treated by intensity-modulated
      radiotherapy with or without chemotherapy.
AB  - PURPOSE: This study was designed to estimate the life expectancy (LE) and quality
      adjusted life expectancy (QALE) in non-metastatic nasopharyngeal cancer (NPC)
      patients. METHODS AND MATERIALS: Patients were eligible for the present study if
      they were diagnosed with NPC and had been treated with intensity-modulated
      radiotherapy (IMRT) between January 1, 2003 and December 31, 2010. The quality of
      life (QOL) data were collected using the questionnaires of the European
      Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 and QLQ-H&N35.
      The LE of NPC patients was obtained using linear extrapolation of a logit
      transformed curve and was adjusted by the corresponding QOL function to calculate
      the QALE. RESULTS: During the study period, 110 patients met the inclusion
      criteria, and 53 of these completed questionnaires. The median follow-up was 65.2
      months (range 4.0-117.3 months). The average LE and QALE were estimated to be
      20.6 years and 11.6 quality-adjusted life years (QALYs) for NPC patients and 24.4
      years and 24.4 QALYs for the reference population, respectively. Compared to the
      reference population, the loss of LE and QALE for NPC patients were 3.8 years and
      12.8 QALYs, respectively. CONCLUSIONS: This study offers a quick overview of the
      LE and the QALE of NPC patients treated with IMRT. Moreover, the results appear
      more understandable than the 5 year survival outcomes when communicating with
      patients or the general population regarding cancer risk. In the future,
      evaluating the robustness of comparative assessments for the outcome of NPC
      patients undergoing different treatment protocols will be possible.

PMID- 24747032
TI  - MicroRNA-138: a potential therapeutic target for head and neck squamous cell
      carcinoma (HNSCC).

PMID- 24747033
TI  - Response from authors of "reliability of post-chemoradiotherapy F-18-FDG PET/CT
      for prediction of locoregional failure in human papillomavirus-associated
      oropharyngeal cancer".

PMID- 24747034
TI  - Therapeutic aspect of oral lichen planus in context to accompanying candidal
      infection.

PMID- 24747035
TI  - Microscopic versus endoscopic pituitary surgery.
AB  - INTRODUCTION AND OBJECTIVE: The endoscopic techniques used in pituitary surgery
      have evolved greatly in recent years. Our objective in this study was to conduct
      a review of the systematic reviews published in the English language literature,
      to examine their consistency and conclusions reached following studies comparing
      microsurgery and endoscopic surgery in hypophyseal surgery. MATERIALS AND
      METHODS: We carried out a bibliographic search on MEDLINE and EMBASE electronic
      databases, selecting those systematic reviews and meta-analyses published from
      the year 2000 until January 2013, focusing on comparisons between microsurgical
      and endoscopic techniques. RESULTS: We concluded with type A consistency that
      hospital stay was shorter and diabetes insipidus and rhinological complications
      were less frequent in the endoscopy group. We concluded with type B consistency
      that lower rates of patient blood loss, shorter operative times, higher rate of
      gross total resection, lesser association to visual impairment and lower rate of
      hypopituitarism were observed in the endoscopy group. Vascular complications and
      cerebrospinal fluid fistulas were reduced with microsurgery. It is crucial to
      perform a combined analysis of all the systematic reviews treating a specific
      topic, observing and analysing the trends and how these are affected by new
      contributions. CONCLUSION: Randomized multicenter studies are necessary to
      resolve the controversy over endoscopic and microsurgical approaches in
      hypophyseal pathology.

PMID- 24747036
TI  - Early vasopressin reduces incidence of new onset arrhythmias.
AB  - PURPOSE: The objective of this study was to determine the effect of early vs late
      vasopressin therapy on catecholamine dose and duration. MATERIALS AND METHODS: We
      conducted a single-center, retrospective chart review of adult patients admitted
      to the medical intensive care unit between January 2010 and December 2011 with
      septic shock requiring catecholamine and vasopressin therapy. Patients were
      included in the early group if vasopressin was initiated within 6 hours and the
      late group if vasopressin was initiated between 6 and 48 hours of
      catecholamine(s). RESULTS: Duration of catecholamine and vasopressin therapy was
      similar between the 35 patients in the early group and the 36 in the late group.
      Vasopressin therapy was associated with a decrease in catecholamine requirements
      in both groups. Early vasopressin was associated with fewer new onset arrhythmias
      (37.1% vs 62.9%, P<.001). There was no difference in mortality, hospital, or
      intensive care unit length of stay between the early and late group vasopressin
      groups (88.6% vs 88.9%, P=1; 14 vs 10 days, P=.48; 9 vs 7 days, P=.71,
      respectively). CONCLUSIONS: Early initiation of vasopressin therapy in adult
      critically ill patients with septic shock was associated with no difference in
      total catecholamine requirements but decreased incidence of new onset
      arrhythmias.

PMID- 24747037
TI  - Measurement of the glucocorticoid receptor: relevance to the diagnosis of
      critical illness-related corticosteroid insufficiency in children.
AB  - Diagnosis and management of critical illness-related corticosteroid insufficiency
      (CIRCI) in children continues to remain difficult and controversial in that no
      consensus for either exists among pediatric critical care physicians. Critical
      illness-related corticosteroid insufficiency is defined as a corticosteroid
      response that is inadequate for the severity of the illness experienced by the
      patient. Critical illness-related corticosteroid insufficiency manifests as an
      insufficient corticosteroid mediated down-regulation of proinflammatory
      cytokines, due to either corticosteroid tissue resistance and/or inadequate
      circulating levels of cortisol. The tissue resistance is likely due to
      alterations in the functionality of the intracellular receptor for
      corticosteroids, the glucocorticoid receptor (GR). This article details the role
      of the GR during critical illness with a focus upon the measurement of the GR, as
      a potentially important means by which to clinically assess the level of
      corticosteroid tissue-resistant in patients suspected of CIRCI. Measurement of
      the GR may be particularly useful as a means by which to determine the judicious
      administration of steroids, maximizing their therapeutic potential, whereas
      minimizing the morbidity that can be associated with their use. 

PMID- 24747038
TI  - The views of health care professionals about selective decontamination of the
      digestive tract: an international, theoretically informed interview study.
AB  - PURPOSE: Selective decontamination of the digestive tract (SDD) as a prophylactic
      intervention improves hospital-acquired infection and survival rates. Uptake of
      SDD is low and remains controversial. This study applied the theoretical domains
      framework to assess intensive care unit clinicians' views about SDD in regions
      with limited or no adoption of SDD. MATERIALS AND METHODS: Participants were
      health professionals with "decisional authority" for the adoption of SDD.
      Semistructured interviews were conducted as the first round of a Delphi study.
      Views about SDD adoption, delivery, and further SDD research were explored.
      Directed content analysis of interview data identified subthemes, which informed
      item development for subsequent Delphi rounds. Linguistic features of interview
      data were also explored. RESULTS: One hundred forty-one participants provided
      interview data. Fifty-six subthemes were identified; 46 were common across
      regions. Beliefs about consequences were the most widely elaborated theme.
      Linguistic features of how participants discussed SDD included caution expressed
      when discussing the risks and benefits and words such as "worry," "anxiety," and
      "fear" when discussing potential antibiotic resistance associated with SDD.
      CONCLUSIONS: We identified salient beliefs, barriers, and facilitators to SDD
      adoption and delivery. What participants said about SDD and the way in which they
      said it demonstrated the degree of clinical caution, uncertainty, and concern
      that SDD evokes.

PMID- 24747040
TI  - Relationship between gastrointestinal dysbiosis and Clostridium botulinum in
      dairy cows.
AB  - The gastrointestinal tract is a balanced ecosystem that can get out of balance
      and predisposed to clostridial diseases or other pathological conditions. The
      objective of the present study was to evaluate the gut microbiota in dairy cows
      suffering from chronic botulism. Cows were investigated for Clostridium (C.)
      botulinum in faeces and rumen fluids. In order to study the relationship between
      botulism and gastrointestinal microbiota, faeces and rumen fluid were tested for
      bacterial composition using conventional microbiological culture techniques and
      fluorescence in situ hybridization (FISH). Protozoa were analyzed in rumen fluid
      microscopically. The presence of C. botulinum was associated with specific
      changes in the faecal microbiota, especially a significant reduction of total
      aerobic bacteria, total anaerobic bacteria, enterococci, Clostridium perfringens
      and yeast and fungi. Also C. botulinum positive rumen fluid had significantly
      more Bacteroides spp., C. histolyticum group, Alfa- proteobacteria,
      Gammaproteobacteria, and sulfate-reducing bacteria; as well as significantly
      fewer Euryaracheota, and the protozoa Epidinium spp. Dasytricha spp.,
      Diplodiniinae spp. and Ophryoscolex spp. In conclusion, C. botulinum is common in
      dairy cows in Germany but the incidence of botulism is associated with microbial
      changes and composition in the gastrointestinal tract. Bacteria, yeast and
      protozoa appear to be crucial in the colonization process; however, the
      chronology of these events and role of each microbial group needs further
      evaluation. 

PMID- 24747039
TI  - Membrane protein structure from rotational diffusion.
AB  - The motional averaging of powder pattern line shapes is one of the most
      fundamental aspects of sold-state NMR. Since membrane proteins in liquid
      crystalline phospholipid bilayers undergo fast rotational diffusion, all of the
      signals reflect the angles of the principal axes of their dipole-dipole and
      chemical shift tensors with respect to the axis defined by the bilayer normal.
      The frequency span and sign of the axially symmetric powder patterns that result
      from motional averaging about a common axis provide sufficient structural
      restraints for the calculation of the three-dimensional structure of a membrane
      protein in a phospholipid bilayer environment. The method is referred to as
      rotationally aligned (RA) solid-state NMR and demonstrated with results on full
      length, unmodified membrane proteins with one, two, and seven trans-membrane
      helices. RA solid-state NMR is complementary to other solid-state NMR methods, in
      particular oriented sample (OS) solid-state NMR of stationary, aligned samples.
      Structural distortions of membrane proteins from the truncations of terminal
      residues and other sequence modifications, and the use of detergent micelles
      instead of phospholipid bilayers have also been demonstrated. Thus, it is highly
      advantageous to determine the structures of unmodified membrane proteins in
      liquid crystalline phospholipid bilayers under physiological conditions. RA solid
      state NMR provides a general method for obtaining accurate and precise structures
      of membrane proteins under near-native conditions.

PMID- 24747041
TI  - Function in patients with cervical radiculopathy or chronic whiplash-associated
      disorders compared with healthy volunteers.
AB  - OBJECTIVE: The purposes of this study were to examine whether any differences in
      function and health exist between patients with cervical radiculopathy (CR) due
      to disk disease scheduled for surgery and patients with chronic whiplash
      associated disorders (WADs) and to compare measures of patients' physical
      function with those obtained from healthy volunteers. METHODS: This is a cross
      sectional study of patients with CR (n = 198) and patients with chronic WAD (n =
      215). Patient data were compared with raw data previously obtained from healthy
      people. Physical measures included cervical active range of motion, neck muscle
      endurance, and hand grip strength. Self-rated measures included pain intensity
      (visual analog scale), neck disability (Neck Disability Index), self-efficacy
      (Self-Efficacy Scale), and health-related quality of life (EuroQol 5-dimensional
      self-classifier). RESULTS: Patient groups exhibited significantly lower
      performance than the healthy group in all physical measures (P < .0005) except
      for neck muscle endurance in flexion for women (P > .09). There was a general
      trend toward worse results in the CR group than the WAD group, with significant
      differences in neck active range of motion, left hand strength for women, pain
      intensity, Neck Disability Index, EuroQol 5-dimensional self-classifier, and Self
      Efficacy Scale (P < .0001). CONCLUSIONS: Patients had worse values than healthy
      individuals in almost all physical measures. There was a trend toward worse
      results for CR than WAD patients.

PMID- 24747042
TI  - Single nucleotide polymorphisms of thymidine kinase and DNA polymerase genes in
      clinical herpes simplex virus type 1 isolates associated with different
      resistance phenotypes.
AB  - The role of mutations in the thymidine kinase (TK, UL23) and DNA polymerase (pol,
      UL30) genes of herpes simplex virus (HSV) for development of different resistance
      phenotypes has to be exactly determined before genotypic resistance testing can
      be implemented in patient's care. Furthermore, the occurrence of cross-resistance
      is of utmost clinical importance. In this study, clinical HSV-1 isolates obtained
      between 2004 and 2011 from 26 patients after stem cell transplantation were
      examined in parallel by phenotypic and genotypic resistance testing. Thirteen
      isolates, which were phenotypically cross-resistant to acyclovir (ACV),
      penciclovir (PCV) and brivudin (BVDU), exhibited consistently frameshift or non
      synonymous mutations in the TK gene known to confer resistance. One of these
      mutations (insertion of C at the nucleotide positions 1061-1065) has not been
      described before. Seven strains, phenotypically resistant to ACV and PCV and,
      except one each, sensitive to BVDU and resistant to foscarnet (FOS), carried
      uniformly resistance-related substitutions in the DNA pol gene. Finally, 3
      isolates, resistant to ACV, PCV and 2 out of these also resistant to BVDU, had
      known but also unclear substitutions in the TK and DNA pol genes, and 3 isolates
      were completely sensitive. In conclusion, clinical ACV-resistant HSV-1 isolates,
      carrying resistance-associated mutations in the TK gene, can be regarded as cross
      resistant to other nucleoside analogs such as BVDU. In contrast, clinical FOS
      resistant HSV-1 strains which are cross-resistant to ACV may be sensitive to
      BVDU. This has to be considered for drug changes in antiviral treatment in case
      of ACV resistance. 

PMID- 24747043
TI  - Plasma acylcarnitines inadequately reflect tissue acylcarnitine metabolism.
AB  - Acylcarnitines have been linked to obesity-induced insulin resistance. However
      the majority of these studies have focused on acylcarnitines in plasma. It is
      currently unclear to what extent plasma levels of acylcarnitines reflect tissue
      acylcarnitine metabolism. We investigated the correlation of plasma acylcarnitine
      levels with selected tissue acylcarnitines as measured with tandem mass
      spectrometry, in both fed and fasted BALB/cJ (BALB) and C57BL/6N (Bl6) mice.
      Fasting affected acylcarnitine levels in all tissues. These changes varied
      substantially between the different tissue compartments. No significant
      correlations were found between plasma acylcarnitine species and their tissue
      counterparts in both mouse strains, with the exception of plasma C4OH-carnitine
      in BALB mice. We suggest that this lack of correlation is due to differences in
      acylcarnitine turnover rates between plasma and tissue compartments and the fact
      that the plasma acylcarnitine profile is a composition of acylcarnitines derived
      from different compartments. Therefore, plasma acylcarnitine levels do not
      reflect tissue levels and should be interpreted with caution. A focus on tissue
      acylcarnitine levels is warranted in metabolic studies. 

PMID- 24747044
TI  - Student receptivity to new school meal offerings: assessing fruit and vegetable
      waste among middle school students in the Los Angeles Unified School District.
AB  - OBJECTIVE: We sought to characterize student receptivity to new menu offerings in
      the Los Angeles Unified School District by measuring the levels of fruit and
      vegetable waste after implementation of changes to the school lunch menu in fall
      2011. METHODS: We measured waste at four randomly selected middle schools in the
      school district, using two sources: a) food prepared and left over after service
      (production waste); and b) food that was selected but not eaten by students
      (plate waste). RESULTS: 10.2% of fruit and 28.7% of vegetable items prepared at
      the four schools were left over after service. Plate waste data, collected from
      2228 students, suggest that many of them did not select fruit (31.5%) or
      vegetable (39.6%) items. Among students who did, many threw fruit and vegetable
      items away without eating a single bite. CONCLUSIONS: Our findings suggest that
      fruit and vegetable waste was substantial and that additional work may be needed
      to increase student selection and consumption of fruit and vegetable offerings.
      Complementary interventions to increase the appeal of fruit and vegetable options
      may be needed to encourage student receptivity to these healthier items in the
      school meal program.

PMID- 24747045
TI  - Kinetic models in industrial biotechnology - Improving cell factory performance.
AB  - An increasing number of industrial bioprocesses capitalize on living cells by
      using them as cell factories that convert sugars into chemicals. These processes
      range from the production of bulk chemicals in yeasts and bacteria to the
      synthesis of therapeutic proteins in mammalian cell lines. One of the tools in
      the continuous search for improved performance of such production systems is the
      development and application of mathematical models. To be of value for industrial
      biotechnology, mathematical models should be able to assist in the rational
      design of cell factory properties or in the production processes in which they
      are utilized. Kinetic models are particularly suitable towards this end because
      they are capable of representing the complex biochemistry of cells in a more
      complete way compared to most other types of models. They can, at least in
      principle, be used to in detail understand, predict, and evaluate the effects of
      adding, removing, or modifying molecular components of a cell factory and for
      supporting the design of the bioreactor or fermentation process. However, several
      challenges still remain before kinetic modeling will reach the degree of maturity
      required for routine application in industry. Here we review the current status
      of kinetic cell factory modeling. Emphasis is on modeling methodology concepts,
      including model network structure, kinetic rate expressions, parameter
      estimation, optimization methods, identifiability analysis, model reduction, and
      model validation, but several applications of kinetic models for the improvement
      of cell factories are also discussed. 

PMID- 24747046
TI  - Production of the sesquiterpenoid (+)-nootkatone by metabolic engineering of
      Pichia pastoris.
AB  - The sesquiterpenoid (+)-nootkatone is a highly demanded and highly valued aroma
      compound naturally found in grapefruit, pummelo or Nootka cypress tree.
      Extraction of (+)-nootkatone from plant material or its production by chemical
      synthesis suffers from low yields and the use of environmentally harmful methods,
      respectively. Lately, major attention has been paid to biotechnological
      approaches, using cell extracts or whole-cell systems for the production of (+)
      nootkatone. In our study, the yeast Pichia pastoris initially was applied as
      whole-cell biocatalyst for the production of (+)-nootkatone from (+)-valencene,
      the abundant aroma compound of oranges. Therefore, we generated a strain co
      expressing the premnaspirodiene oxygenase of Hyoscyamus muticus (HPO) and the
      Arabidopsis thaliana cytochrome P450 reductase (CPR) that hydroxylated
      extracellularly added (+)-valencene. Intracellular production of (+)-valencene by
      co-expression of valencene synthase from Callitropsis nootkatensis resolved the
      phase-transfer issues of (+)-valencene. Bi-phasic cultivations of P. pastoris
      resulted in the production of trans-nootkatol, which was oxidized to (+)
      nootkatone by an intrinsic P. pastoris activity. Additional overexpression of a
      P. pastoris alcohol dehydrogenase and truncated hydroxy-methylglutaryl-CoA
      reductase (tHmg1p) significantly enhanced the (+)-nootkatone yield to 208mg L(-1)
      cell culture in bioreactor cultivations. Thus, metabolically engineered yeast P.
      pastoris represents a valuable, whole-cell system for high-level production of
      (+)-nootkatone from simple carbon sources.

PMID- 24747048
TI  - Beyond DnaA: the role of DNA topology and DNA methylation in bacterial
      replication initiation.
AB  - The replication of chromosomal DNA is a fundamental event in the life cycle of
      every cell. The first step of replication, initiation, is controlled by multiple
      factors to ensure only one round of replication per cell cycle. The process of
      initiation has been described most thoroughly for bacteria, especially
      Escherichia coli, and involves many regulatory proteins that vary considerably
      between different species. These proteins control the activity of the two key
      players of initiation in bacteria: the initiator protein DnaA and the origin of
      chromosome replication (oriC). Factors involved in the control of the
      availability, activity, or oligomerization of DnaA during initiation are
      generally regarded as the most important and thus have been thoroughly
      characterized. Other aspects of the initiation process, such as origin
      accessibility and susceptibility to unwinding, have been less explored. However,
      recent findings indicate that these factors have a significant role. This review
      focuses on DNA topology, conformation, and methylation as important factors that
      regulate the initiation process in bacteria. We present a comprehensive summary
      of the factors involved in the modulation of DNA topology, both locally at oriC
      and more globally at the level of the entire chromosome. We show clearly that the
      conformation of oriC dynamically changes, and control of this conformation
      constitutes another, important factor in the regulation of bacterial replication
      initiation. Furthermore, the process of initiation appears to be associated with
      the dynamics of the entire chromosome and this association is an important but
      largely unexplored phenomenon. 

PMID- 24747047
TI  - Binding polarity of RPA to telomeric sequences and influence of G-quadruplex
      stability.
AB  - Replication protein A (RPA) is a single-stranded DNA binding protein that plays
      an essential role in telomere maintenance. RPA binds to and unfolds G-quadruplex
      (G4) structures formed in telomeric DNA, thus facilitating lagging strand DNA
      replication and telomerase activity. To investigate the effect of G4 stability on
      the interactions with human RPA (hRPA), we used a combination of biochemical and
      biophysical approaches. Our data revealed an inverse relationship between G4
      stability and ability of hRPA to bind to telomeric DNA; notably small G4 ligands
      that enhance G4 stability strongly impaired G4 unfolding by hRPA. To gain more
      insight into the mechanism of binding and unfolding of telomeric G4 structures by
      RPA, we carried out photo-crosslinking experiments to elucidate the spatial
      arrangement of the RPA subunits along the DNA strands. Our results showed that
      RPA1 and RPA2 are arranged from 5' to 3' along the unfolded telomeric G4, as
      already described for unstructured single-stranded DNA, while no contact is
      possible with RPA3 on this short oligonucleotide. In addition, these data are
      compatible with a 5' to 3' directionality in G4 unfolding by hRPA. 

PMID- 24747049
TI  - Gene-specific methylation control of H3K9 and H3K36 on neurotrophic BDNF versus
      astroglial GFAP genes by KDM4A/C regulates neural stem cell differentiation.
AB  - Neural stem cell (NSC) state and fate depend on spatially and temporally
      synchronized transcriptional and epigenetic regulation of the expression of
      extrinsic signaling factors and intrinsic cell-specific genes, but the functional
      roles for chromatin-modifying enzymes in neural differentiation remain poorly
      understood. Here we show that the histone demethylases KDM4A (JMJD2A) and KDM4C
      (JMJD2C) are essential for proper differentiation of NSCs in vitro and in vivo.
      KDM4A/C were required for neuronal differentiation, survival and expression of
      the neurotrophic signaling factor BDNF in association with promoter H3K9
      demethylation and RNA polymerase II recruitment. Unexpectedly, KDM4A/C were
      essential for selective H3K36 demethylation and loss of RNA polymerase II
      recruitment in transcribed regions of the astrocyte-characteristic gene GFAP,
      thereby in parallel repressing astrocytic differentiation by control of
      elongation. We propose that gene- and lysine-specific KDM4A/C-mediated control of
      histone methylation and thereby regulation of intrinsic factors and signaling
      factors such as BDNF provide a novel control mechanism of lineage decision.

PMID- 24747050
TI  - Alanine scanning mutagenesis identifies an asparagine-arginine-lysine triad
      essential to assembly of the shell of the Pdu microcompartment.
AB  - Bacterial microcompartments (MCPs) are the simplest organelles known. They
      function to enhance metabolic pathways by confining several related enzymes
      inside an all-protein envelope called the shell. In this study, we investigated
      the factors that govern MCP assembly by performing scanning mutagenesis on the
      surface residues of PduA, a major shell protein of the MCP used for 1,2
      propanediol degradation. Biochemical, genetic, and structural analysis of 20
      mutants allowed us to determine that PduA K26, N29, and R79 are crucial residues
      that stabilize the shell of the 1,2-propanediol MCP. In addition, we identify two
      PduA mutants (K37A and K55A) that impair MCP function most likely by altering the
      permeability of its protein shell. These are the first studies to examine the
      phenotypic effects of shell protein structural mutations in an MCP system. The
      findings reported here may be applicable to engineering protein containers with
      improved stability for biotechnology applications. 

PMID- 24747051
TI  - Folding pathways of the Tetrahymena ribozyme.
AB  - Like many structured RNAs, the Tetrahymena group I intron ribozyme folds through
      multiple pathways and intermediates. Under standard conditions in vitro, a small
      fraction reaches the native state (N) with kobs ~ 0.6 min(-1), while the
      remainder forms a long-lived misfolded conformation (M) thought to differ in
      topology. These alternative outcomes reflect a pathway that branches late in
      folding, after disruption of a trapped intermediate (Itrap). Here we use
      catalytic activity to probe the folding transitions from Itrap to the native and
      misfolded states. We show that mutations predicted to weaken the core helix P3 do
      not increase the rate of folding from Itrap but they increase the fraction that
      reaches the native state rather than forming the misfolded state. Thus, P3 is
      disrupted during folding to the native state but not to the misfolded state, and
      P3 disruption occurs after the rate-limiting step. Interestingly, P3
      strengthening mutants also increase native folding. Additional experiments show
      that these mutants are rapidly committed to folding to the native state, although
      they reach the native state with approximately the same rate constant as the wild
      type ribozyme (~1 min(-1)). Thus, the P3-strengthening mutants populate a
      distinct pathway that includes at least one intermediate but avoids the M state,
      most likely because P3 and the correct topology are formed early. Our results
      highlight multiple pathways in RNA folding and illustrate how kinetic
      competitions between rapid events can have long-lasting effects because the
      "choice" is enforced by energy barriers that grow larger as folding progresses.

PMID- 24747052
TI  - Co-crystallization with conformation-specific designed ankyrin repeat proteins
      explains the conformational flexibility of BCL-W.
AB  - BCL-W is a member of the BCL-2 family of anti-apoptotic proteins. A key event in
      the regulation of apoptosis is the heterodimerization between anti-apoptotic and
      pro-apoptotic family members, which involves a conserved surface-exposed groove
      on the anti-apoptotic proteins. Crystal structures of the ligand binding
      competent conformation exist for all anti-apoptotic family members, with the
      exception of BCL-W, due to the flexibility of the BCL-W groove region. Existing
      structures had suggested major deviations of the BCL-W groove region from the
      otherwise structurally highly related remaining anti-apoptotic family members. To
      capture its ligand binding-competent conformation by counteracting the
      conformational flexibility of the BCL-W groove, we had selected high-affinity
      groove-binding designed ankyrin repeat proteins (DARPins) using ribosome display.
      We now determined two high-resolution crystal structures of human BCL-W in
      complex with different DARPins at resolutions 1.5 and 1.85A, in which the
      structure of BCL-W is virtually identical, and BCL-W adopts a conformation
      extremely similar to the ligand-free conformation of its closest relative BCL-XL
      in both structures. However, distinct differences to all previous BCL-W
      structures are evident, notably in the ligand-binding region. We provide the
      first structural explanation for the conformational flexibility of the BCL-W
      groove region in comparison to other BCL-2 family members. Due to the importance
      of the anti-apoptotic BCL-2 family as drug targets, the presented crystal
      structure of ligand binding-competent BCL-W may serve as a valuable basis for
      structure-based drug design in the future and provides a missing piece for the
      structural characterization of this protein family. 

PMID- 24747053
TI  - Carapanolides C-I from the seeds of andiroba (Carapa guianensis, Meliaceae).
AB  - Five new mexicanolide-type limonoids, carapanolides C-G (1-5), together with two
      new phragmalin-type limonoids, carapanolides H-I (6, 7), were isolated from the
      oil of Carapa guianasis AUBLET (Meliaceae) seeds. Their structures were
      elucidated on the basis of spectroscopic analyses using 1D and 2D NMR spectra and
      FABMS. Carapanolides C (1), E (3), and I (7) exhibited moderate activity in the
      P388 (IC50 17.9 MUM in 1, 15.8 MUM in 3) and L1210 cell lines (IC50 13.3 MUM in
      1, 18.1 MUM in 3, 16.9 MUM in 7). On the other hand, Carapanolide D (2) exhibited
      a strong inhibitory effect in the HL-60 cell line (IC50 11.0 MUM), Carapanolides
      F (4) showed inhibitory activity in the L1210 cell line (IC50 15.9 MUM), and the
      cytotoxic activity of Carapanolides I (7) was moderate in all cell lines.

PMID- 24747054
TI  - TAK1-binding proteins (TAB1 and TAB2) in grass carp (Ctenopharyngodon idella):
      identification, characterization, and expression analysis after infection with
      Ichthyophthirius multifiliis.
AB  - Transforming growth factor-beta activated kinase-1 (TAK1) is a key regulatory
      molecule in toll-like receptor (TLR), interleukin-1 (IL-1), and tumor necrosis
      factor (TNF) signaling pathways. The activation of TAK1 is specifically regulated
      by two TAK1-binding proteins, TAB1 and TAB2. However, the roles of TAB1 and TAB2
      in fish have not been reported to date. In the present study, TAB1 (CiTAB1) and
      TAB2 (CiTAB2) in grass carp (Ctenopharyngodon idella) were identified and
      characterized, and their expression profiles were analyzed after fish were
      infected with the pathogenic ciliate Ichthyophthirius multifiliis. The full
      length CiTAB1 cDNA is 1949 bp long with an open reading frame (ORF) of 1497 bp
      that encodes a putative protein of 498 amino acids containing a typical PP2Cc
      domain. The full-length CiTAB2 cDNA is 2967 bp long and contains an ORF of 2178
      bp encoding a putative protein of 725 amino acids. Protein structure analysis
      revealed that CiTAB2 consists of three main structural domains: an N-terminal CUE
      domain, a coiled-coil domain, and a C-terminal ZnF domain. Multiple sequence
      alignment showed that CiTAB1 and CiTAB2 share high sequence identity with other
      known TAB1 and TAB2 proteins, and several conserved phosphorylation sites and an
      O-GlcNAc site were deduced in CiTAB1. Phylogenetic tree analysis demonstrated
      that CiTAB1 and CiTAB2 have the closest evolutionary relationship with TAB1 and
      TAB2 of Danio rerio, respectively. CiTAB1 and CiTAB2 were both widely expressed
      in all examined tissues with the highest levels in the heart and liver,
      respectively. After infection with I. multifiliis, the expressions of CiTAB1 and
      CiTAB2 were both significantly up-regulated in all tested tissues at most time
      points, which indicates that these proteins may be involved in the host immune
      response against I. multifiliis infection. 

PMID- 24747055
TI  - Identification and characterization of miR-92a and its targets modulating Vibrio
      splendidus challenged Apostichopus japonicus.
AB  - miR-92a is a kind of disease related fine-tuning regulator which is not only
      related with tumorigenesis and tumor development but also participates in host
      pathogen interaction in vertebrates. In present study, the potential targets of
      miR-92a in Apostichopus japonicus coelomocytes were screened by high-throughout
      sequencing and PCR approaches. Total of 10 annotated candidates were identified
      by hybrid PCR, and 23 were verified from RNA-seq, in which SMURF, PCBP and MEGF
      were found in both methods. The expression patterns of miR-92a and some putative
      targets were further characterized by qPCR at cell and individual levels. Vibrio
      splendidus and LPS exposure could significantly increase the expression level of
      sea cucumber miR-92a at all examined time points. Accordingly, strictly negative
      correlation expression profiles were detected in two candidates genes of MEGF and
      SMURF, suggesting that these two genes showed higher possibilities to be the
      targets of miR-92a in sea cucumber. Overall, the present work will enhance our
      understanding in the context of miR-92a modulating the interaction of sea
      cucumber upon pathogen challenged. 

PMID- 24747056
TI  - Hepatic encephalopathy is associated with slowed and delayed stimulus-associated
      somatosensory alpha activity.
AB  - OBJECTIVE: Hepatic encephalopathy (HE) is associated with motor symptoms and
      attentional deficits, which are related to pathologically slowed oscillatory
      brain activity. Here, potential alterations of oscillatory activity in the
      somatosensory system were investigated. METHODS: 21 patients with liver cirrhosis
      and varying HE severity and 7 control subjects received electrical stimulation of
      the right median nerve while brain activity was recorded using
      magnetoencephalography (MEG). Oscillatory activity within the contralateral
      primary somatosensory cortex (S1) and its stimulus-induced modulation were
      analyzed as a function of disease severity. RESULTS: Median nerve stimuli evoked
      an early broadband power increase followed by suppression and then rebound of S1
      alpha and beta activity. Increasing HE severity as quantified by the critical
      flicker frequency (CFF) was associated with a slowing of the alpha peak frequency
      and a delay of the alpha rebound. CONCLUSION: The present results provide the
      first evidence for a slowing of oscillatory activity in the somatosensory system
      in HE in combination with a previously unknown deficit of S1 in adjusting
      activation levels back to baseline. SIGNIFICANCE: These findings advance the
      understanding of the manifold symptoms of HE by strengthening the theory that
      disease related slowing of oscillatory brain activity also affects the
      somatosensory system.

PMID- 24747057
TI  - Activation deficit correlates with weakness in chronic stroke: evidence from
      evoked and voluntary EMG recordings.
AB  - OBJECTIVE: To use evoked (M-wave) and voluntary (during maximal voluntary
      contraction (MVC)) EMG recordings to estimate the voluntary activation level in
      chronic stroke. METHODS: Nine chronic hemiparetic stroke subjects participated in
      the experiment. M-wave (EMGM-wave) and MVC (EMGMVC) EMG values of the biceps
      brachii muscles were recorded. RESULTS: Peak torque was significantly smaller on
      the impaired than non-impaired side. EMGM-wave was also significantly smaller on
      the impaired than non-impaired side. However, the normalized EMGM-wave/TorqueMVC
      ratio was not significantly different between two sides. In contrast, both
      absolute EMGMVC and normalized EMGMVC/TorqueMVC were smaller on the impaired than
      non-impaired side. The voluntary activation level, EMGMVC/M-wave, was also
      smaller on the impaired than non-impaired side. The voluntary activation level on
      the impaired side was highly correlated with weakness (R=0.72), but very low
      (R=0.32) on the non-impaired side. CONCLUSION: Collectively, our findings suggest
      that both peripheral and central factors contribute to post-stroke weakness, but
      activation deficit correlates most closely with weakness as estimated from
      maximum voluntary torque generation. SIGNIFICANCE: These findings serve to
      highlight the potential benefit from high-intensity exercises to enhance central
      activation for facilitation of motor recovery.

PMID- 24747058
TI  - Autoimmune diseases in HIV-infected patients: 52 cases and literature review.
AB  - OBJECTIVES: 1) To describe autoimmune diseases (AD) in HIV-infected people; and
      2) to perform a literature review concerning this issue. DESIGN: 52 HIV-infected
      patients that presented an AD in 14 medical departments in Paris and Ile-de
      France area were retrospectively included in this study. RESULTS: The ADs were
      vasculitis (11), immune cytopenias (8), rheumatic diseases (8), lupus (7),
      sarcoidosis (7), thyroid diseases (6), hepatic diseases (5), and antiphospholipid
      syndrome (4). Four patients presented 2 ADs. In 5 patients the AD preceded HIV
      infection, in 14 HIV infection was diagnosed at the same time as the AD and 34
      were HIV-infected when they developed an AD. 40 ADs (80%) occurred in patients
      with a CD4 T lymphocyte count of more than 200/mm(3). Cases of autoimmune
      hemolytic anemia occurred only in patients severely immunodepressed. In five
      patients (a vasculitis case, a sarcoidosis case, three thyroid disease cases) the
      AD presented as a form of immune restoration inflammatory syndrome (IRIS). Some
      ADs allowed HIV-infection diagnosis at a stage of moderate immune deficiency
      (vasculitis, antiphospholipid syndrome, immune thrombocytopenia). 37 patients
      received immunosuppressant treatments with good tolerance. These results confirm
      in a large series of patients previous data concerning autoimmune diseases
      occurrence in HIV-infected people. CONCLUSION: In the HAART era, when HIV
      infected people are treated more and more early, autoimmune diseases can occur,
      mainly at the phase of immunological recovery. HIV infection should not limit
      immunosuppressant treatment use.

PMID- 24747059
TI  - Bariatric surgery and diet-induced long-term caloric restriction protect
      subcutaneous adipose-derived stromal/progenitor cells and prolong their life span
      in formerly obese humans.
AB  - A key effect of prolonged reducing diets and bariatric surgeries in formerly
      obese people is long-term caloric restriction (CR). The analysis of the impact of
      these interventions on specific tissues will contribute to a better understanding
      of their mechanisms of action. The physiological functions of subcutaneous white
      adipose tissues are mainly fulfilled by adipocytes arising out of adipose-derived
      stromal/progenitor cells (ASCs), which are crucial for adipose tissue
      homeostasis. In the present study we analyzed ASC from age-matched long-term
      calorically restricted formerly obese (CRD), obese (OD) and normal weight donors
      (NWDs). We demonstrate that ASC derived from CRD has a significant longer
      replicative lifespan than ASC isolated from OD and NWD. This correlated with
      strongly reduced DNA-damage and improved survival of the CRD ASC, both are
      hallmarks of CR. The adipogenic capacity was significantly lower in ASC derived
      from CRD than that from OD, as shown by reduced expression of the adipogenic key
      regulator PPARgamma2 and the differentiation marker FABP4. The adipogenic
      capacity of ASCs from CRD and NWD differed only slightly. In conclusion, we
      provide evidence that bariatric surgery and diet-induced long-term CR
      substantially reprogram ASCs in formerly obese humans, comprising reduced DNA
      damage, improved viability, extended replicative lifespan and reduced adipogenic
      differentiation potential. 

PMID- 24747060
TI  - Partial pericardial defect with left auricular herniation in a dog with syncope.
AB  - Pericardial defects are rare in both people and dogs. They may be congenital or
      acquired in origin, and partial or total in extent. Commonly, pericardial defects
      are incidental findings at autopsy; however, diagnostic methods such as thoracic
      radiography and echocardiography can be useful in the ante mortem diagnosis of
      pericardial defects. This report describes the first case of a dog with syncope,
      supraventricular tachycardia, and a partial left pericardial defect with
      herniation of the left auricle for which extensive ante mortem diagnostic
      information was available. Partial absence of the pericardium should be
      considered in dogs with disproportionate enlargement of cardiac chambers for
      which other congenital and acquired heart diseases are ruled out. 

PMID- 24747061
TI  - Double-outlet right atrium in a 9 year-old cat.
AB  - Double-outlet right atrium (DORA) is a type of atrioventricular septal defect
      that is described as an extreme leftward deviation of the lower portion of the
      interatrial septum, resulting in insertion into the atrial wall left and
      posterior to the mitral orifice. This rare anomaly, which has been reported in
      humans and only just recently in cats, was identified by transthoracic
      echocardiography in a 9 year-old cat that was presented for further evaluation of
      a tachyarrhythmia and cardiomegaly. This case report describes the diagnostic
      findings in this cat and summarizes the anatomy, classification and clinical
      consequences of this rare congenital heart defect. 

PMID- 24747062
TI  - A case of multifocal spinal tuberculosis from Medieval Rhodes.

PMID- 24747063
TI  - Synthesis of novel spiropyrazoline oxindoles and evaluation of cytotoxicity in
      cancer cell lines.
AB  - A series of novel spiropyrazoline oxindole derivatives was synthesized by 1,3
      dipolar cycloaddition reaction. The compounds were screened for their in vitro
      cytotoxic activity against MCF-7 breast cancer cell line (estrogen receptor
      positive (ER+) and human epidermal growth factor receptor 2 negative (HER2-)). Of
      the nineteen spiropyrazoline oxindoles tested, six compounds have a GI50 below 12
      MUM The most potent compounds in this series were also evaluated against MDA-MB
      231 breast cancer cell line (ER- and HER2-). Two spiropyrazoline oxindoles were
      highly selective between MCF-7 tumor cells and MDA-MB-231 tumor cells. More
      importantly, they were noncytotoxic against HEK 293T non tumor derived cell
      lines. 

PMID- 24747064
TI  - Targeting triple-negative breast cancer cells with 6,7-bis(hydroxymethyl)-1H,3H
      pyrrolo[1,2-c]thiazoles.
AB  - Further studies on 6,7-bis(hydroxymethyl)-1H,3H-pyrrolo[1,2-c]thiazoles as
      anticancer agents against breast cancer are reported, allowing to demonstrate the
      potential of these compounds for the therapy of the triple-negative breast
      cancer, the most challenging tumors in clinical practice. These compounds were
      assayed for their in vitro cytotoxicity on several human breast cancer cell lines
      (MCF7, HCC1954 and HCC1806 cell lines). Particularly interesting were the results
      obtained for 4-hydroxyphenyl substituted derivative, which proved to be the most
      promising compound regarding HCC1806 cell line, a triple-negative breast cancer.
      The effects of the two most active compounds on cell survival, viability, cell
      cycle, DNA damage and expression of proteins related to cell death pathways were
      studied. The reported results consolidate the potential of 6,7-bis(hydroxymethyl)
      1H,3H-pyrrolo[1,2-c]thiazoles for the therapy of breast cancer, particularly the
      triple-negative. 

PMID- 24747065
TI  - Synthesis and biological activity of 4-aryl-3-benzoyl-5-phenylspiro[pyrrolidine
      2.3'-indolin]-2'-one derivatives as novel potent inhibitors of advanced glycation
      end product.
AB  - Diabetic complications and their detrimental effects caused by sugar derived
      substances, have been the serious issue for the last few years and have yet not
      been fully combated. The key point of the present study is to synthesize some
      newer chemical entities which can eradicate such ailments to the maximum possible
      extent. So with this aim synthesis of some biologically interesting spiro
      indolone-pyrrolidine derivatives was accomplished by 1,3-dipolar cycloaddition
      reaction of azomethine ylide 6 generated in situ from isatin and benzyl amine
      with the substituted alpha,beta-unsaturated carbonyl compounds 3 as
      dipolarophile, leading to the formation of new 4-aryl-3-benzoyl-5
      phenylspiro[pyrrolidine-2.3'-indolin]-2'-one derivatives 7 stereoselectively in
      excellent yields. The synthesized compounds have been screened for their advanced
      glycation end (AGE) product formation inhibitory activity on the basis of their
      ability to inhibit the formation of AGEs in the bovine serum albumin (BSA)
      glucose assay and have been found to exhibit significant activity against AGE
      formation. 

PMID- 24747067
TI  - Familiarity is more important than phenotypic similarity in shaping social
      relationships in a facultative female dispersed primate, Colobus vellerosus.
AB  - Animals often bias affiliative behaviors toward kin, but it is unclear what
      mechanism most species use to discriminate kin. We investigated if facultative
      dispersed female primates use phenotype matching and/or familiarity to
      discriminate female kin. We studied 38 adult female Colobus vellerosus at Boabeng
      Fiema, Ghana. We determined dyadic co-residency status and age proximity using
      long-term demographic data, R-values from 17 short tandem repeat loci, and
      interaction rates using focal samples collected during one year. Approach rates
      were not strongly affected by how long females had resided together, which
      contrasts to the familiarity hypothesis. Females approached and groomed maternal
      kin more than other females, which supports the mother-mediated familiarity
      hypothesis. Females did not discriminate paternal half siblings from non-kin, and
      they did not prefer to interact with females of similar age. Short-term co
      resident kin did not bias affiliation toward each other, indicating that female
      colobus cannot consistently recognize less familiar kin via phenotype matching or
      that biasing behaviors toward less familiar kin is not beneficial. Despite
      showing facultative dispersal that may reduce the accuracy of using familiarity
      as a kin recognition mechanism, female choice of social partners was based on
      familiarity, which conforms to the pattern observed in many female philopatric
      primates. 

PMID- 24747066
TI  - Brominated polyunsaturated lipids from the Chinese sponge Xestospongia
      testudinaria as a new class of pancreatic lipase inhibitors.
AB  - Chemical analysis of the Chinese marine sponge Xestospongia testudinaria afforded
      a library of brominated polyunsaturated lipids including eight new compounds,
      named xestonarienes A-H (3-10) and thirteen known analogues (11-23). The
      structures of the new compounds were elucidated by detailed spectroscopic
      analysis and by comparison with literature data. The isolated lipids were
      evaluated for their inhibitory activity against pancreatic lipase (PL), an
      essential enzyme for efficient fat digestion and the major metabolite, 14,
      exhibited a marked inhibitory activity (IC50 = 3.11 MUM), similar to that of the
      positive control Orlistat (IC50 = 0.78 MUM). The preliminary structure-activity
      relationships on the series of compounds clearly evidenced that a terminal (E)
      enyne functionality, a diyne within the chain, and methyl ester group are all key
      functional groups for the activity of this class of PL inhibitors. Further
      biological investigation on compound 14 revealed a significant decrease in the
      plasma triglyceride level following an oral lipid challenge in C57BLKS/J male
      mice. Acute toxicology study demonstrated that compound 14 was non-toxic up to
      1600 mg/kg p.o in mice. This is the first report of the PL inhibitory activity
      for brominated polyunsaturated lipids and the obtained results qualify compound
      14 as a potent and bioavailable drug candidate for a mild and safe treatment to
      prevent and reduce obesity. 

PMID- 24747068
TI  - Ovarian development in a primitively eusocial wasp: social interactions affect
      behaviorally dominant and subordinate wasps in opposite directions relative to
      solitary females.
AB  - In many primitively eusocial wasp species new nests are founded either by a
      single female or by a small group of females. In the single foundress nests, the
      lone female develops her ovaries, lays eggs as well as tends her brood. In
      multiple foundress nests social interactions, especially dominance-subordinate
      interactions, result in only one 'dominant' female developing her ovaries and
      laying eggs. Ovaries of the remaining 'subordinate' cofoundresses remain
      suppressed and these individuals function as workers and tend the dominant's
      brood. Using the tropical, primitively eusocial polistine wasp Ropalidia
      marginata and by comparing wasps held in isolation and those kept as pairs in the
      laboratory, we demonstrate that social interactions affect ovarian development of
      dominant and subordinate wasps among the pairs in opposite directions,
      suppressing the ovaries of the subordinate member of the pair below that of
      solitary wasps and boosting the ovaries of dominant member of the pair above that
      of solitary females. In addition to being of physiological interest, such mirror
      image effects of aggression on the ovaries of the aggressors and their victims,
      suggest yet another mechanism by which subordinates can enhance their indirect
      fitness and facilitate the evolution of worker behavior by kin selection. 

PMID- 24747069
TI  - Evidence that histidine forms a coordination bond to the A(0A) and A(0B)
      chlorophylls and a second H-bond to the A(1A) and A(1B) phylloquinones in
      M688H(PsaA) and M668H(PsaB) variants of Synechocystis sp. PCC 6803.
AB  - The axial ligands of the acceptor chlorophylls, A(0A) and A(0B), in Photosystem I
      are the Met sulfur atoms of M688(PsaA) and M668(PsaB). To determine the role of
      the Met, His variants were generated in Synechocystis sp. PCC 6803. Molecular
      dynamics simulations on M688H(PsaA) show that there exist low energy
      conformations with the His coordinated to A(0A) and possibly H-bonded to A(1A).
      Transient EPR studies on M688H(PsaA) indicate a more symmetrical electron spin
      distribution in the A(1A) phyllosemiquinone ring consistent with the presence of
      an H-bond to the C1 carbonyl. Ultrafast optical studies on the variants show that
      the 150fs charge separation between P700 and A(0) remains unaffected. Studies on
      the ns timescale show that 57% of the electrons are transferred from A(0A)(-) to
      A(1A) in M688H(PsaA) and 48% from A(0B)(-) to A(1B) in M668H(PsaB); the remainder
      recombine with P700(+) with 1/e times of 25ns and 37ns, respectively. Those
      electrons that reach A(1A) and A(1B) in the branch carrying the mutation are not
      transferred to FX, but recombine with P700(+) with 1/e times of ~15MUs and ~5MUs,
      respectively. Hence, the His is coordinated to A0 in all populations, but in a
      second population, the His may be additionally H-bonded to A(1). Electron
      transfer from A(0) to A(1) occurs only in the latter, but the higher redox
      potentials of A(0) and A(1) as a result of the stronger coordination bond to A(0)
      and the proposed second H-bond to A(1) preclude electron transfer to the Fe/S
      clusters.

PMID- 24747070
TI  - Transcriptome profiling to identify genes involved in pathogenicity of Valsa mali
      on apple tree.
AB  - Apple Valsa canker, caused by the fungus Valsa mali (Vm), is one of the most
      destructive diseases of apple in China. A better understanding of this host
      pathogen interaction is urgently needed to improve management strategies. In the
      current study we sequenced the transcriptomes of Vm during infection of apple
      bark and mycelium grown in axenic culture using Illumina RNA-Seq technology. We
      identified 437 genes that were differentially expressed during fungal infection
      compared to fungal mycelium grown in axenic culture. One hundred and thirty nine
      of these 437 genes showed more than two fold higher transcript abundance during
      infection. GO and KEGG enrichment analyses of the up-regulated genes suggest
      prevalence of genes associated with pectin catabolic, hydrolase activity and
      secondary metabolite biosynthesis during fungal infection. Some of the up
      regulated genes associated with loss of pathogenicity and reduced virulence
      annotated by host-pathogen interaction databases may also be involved in cell
      wall hydrolysis and secondary metabolite transport, including a glycoside
      hydrolase family 28 protein, a peptidase and two major facilitator superfamily
      proteins. This highlights the importance of secondary metabolites and cell wall
      hydrolases during establishment of apple Valsa canker. Functional verification of
      the genes involved in pathogenicity of Vm will allow us to better understand how
      the fungus interferes with the host machinery and assists in apple canker
      establishment.

PMID- 24747071
TI  - Association of single-nucleotide polymorphisms in TLR7 (Gln11Leu) and TLR9
      (1635A/G) with a higher CD4T cell count during HIV infection.
AB  - BACKGROUND: Toll-like receptors (TLRs) are essential elements of the innate
      immune response to different infections including HIV-1 infection. The single
      nucleotide polymorphisms (SNPs) in TLRs have been associated with CD4T cell count
      and HIV disease progression. The TLR7 (Gln11Leu) SNP was shown to be associated
      with a rapid decline of CD4T cell count. A relation between TLR9 (1635A/G) SNP
      and CD4T cells count in HIV-infected patients is suggested, although the outcome
      associated with this SNP is still controversial. OBJECTIVES: To determine the
      relation of the TLR7 (Gln11Leu) and TLR9 (1635A/G) SNPs with the damage to the
      immune system during HIV infection as reflected by the average CD4T cell count.
      METHODS: A total of 63 HIV-infected patients and 100 healthy individuals
      (controls) were enrolled in this study. The above named SNPs were analyzed after
      amplification of the regions that potentially contain the SNPs by polymerase
      chain reaction (PCR) and sequencing of the PCR products. The frequency of these
      SNPs and their relation with the CD4T cell count were investigated. RESULTS: The
      TLR7 (AA) genotype 'Gln' had a trend toward being associated with a CD4T cell
      count >400cells/MUl after controlling viremia via HAART. Additionally, the TLR9
      1635 (GG) genotype was associated with a low average CD4T cell count and the TLR9
      1635 (AG) genotype was significantly related to a higher average CD4T cell count
      during the viremic period in HIV-infected patients. CONCLUSION: The results of
      this longitudinal study supports the presence of an association between the TLR9
      (1635A/G) genotype and the CD4T cell count, which helps clarifying the
      controversial results regarding this association. It also suggests that the CD4T
      cell count during the viremic period might be linked to the combination of both
      TLR7 (Gln11Leu) and TLR9 (1635A/G) genotypes. These results may help predicting
      the damage to the immune system, and thus impacting the planning for novel anti
      HIV strategies.

PMID- 24747072
TI  - CD26-mediated regulation of periostin expression contributes to migration and
      invasion of malignant pleural mesothelioma cells.
AB  - Malignant pleural mesothelioma (MPM) is an aggressive malignancy arising from
      mesothelial lining of pleura. It is generally associated with a history of
      asbestos exposure and has a very poor prognosis, partly due to the lack of a
      precise understanding of the molecular mechanisms associated with its malignant
      behavior. In the present study, we expanded on our previous studies on the
      enhanced motility and increased CD26 expression in MPM cells, with a particular
      focus on integrin adhesion molecules. We found that expression of CD26
      upregulates periostin secretion by MPM cells, leading to enhanced MPM cell
      migratory and invasive activity. Moreover, we showed that upregulation of
      periostin expression results from the nuclear translocation of the basic helix
      loop-helix transcription factor Twist1, a process that is mediated by CD26
      associated activation of Src phosphorylation. While providing new and profound
      insights into the molecular mechanisms involved in MPM biology, these findings
      may also lead to the development of novel therapeutic strategies for MPM. 

PMID- 24747073
TI  - A novel role for IQGAP1 protein in cell motility through cell retraction.
AB  - IQGAP1 has emerged as a key component in the regulation of cytoskeleton dynamics
      during cell migration, maintenance of adherens junctions, microbial pathogenesis
      and intracellular trafficking. IQGAP1 is known to localize to the protruding edge
      of lamellipodia in a variety of cell types and interact with regulators of actin
      dynamics. Here, we provide evidence suggesting a novel role of IQGAP1 in cell
      motility through cell edge retraction. In some of the cell lines examined, IQGAP1
      was markedly separated from WAVE localization suggesting IQGAP1 may localize to
      retracting edges. B16F10 mouse melanoma cells exhibited the most restricted
      separation in which the appearance of GFP-IQGAP1 correlated with cell edge
      retraction velocity and the disappearance of mCherry-Arp3. These results
      demonstrate that in some cell types IQGAP1 may function to promote cell
      retraction not lamellipodium edge protrusion. In addition, we examined co
      localization of IQGAP1 with adhesion site markers, myosin IIA, calmodulin and
      IQGAP2. In areas rich in IQGAP1 there was decreased immunofluorescence staining
      of vinculin, paxillin and phosphorylated-tyrosine indicating adhesion site
      disassembly. Interestingly, calmodulin, but not myosin IIA or IQGAP2, co
      localized with IQGAP1 in areas of cell retraction. Overall these results suggest
      a new role of IQGAP1, distinct form IQGAP2, in cell migration through up
      regulation of contractility and downregulation of adhesion sites potentially
      through calmodulin interaction.

PMID- 24747074
TI  - Luteolin inhibits the Nrf2 signaling pathway and tumor growth in vivo.
AB  - Nuclear factor erythroid 2-related factor 2 (Nrf2) is over-expressed in many
      types of tumor, promotes tumor growth, and confers resistance to anticancer
      therapy. Hence, Nrf2 is regarded as a novel therapeutic target in cancer.
      Previously, we reported that luteolin is a strong inhibitor of Nrf2 in vitro.
      Here, we showed that luteolin reduced the constitutive expression of NAD(P)H
      quinone oxidoreductase 1 in mouse liver in a time- and dose-dependent manner.
      Further, luteolin inhibited the expression of antioxidant enzymes and glutathione
      transferases, decreasing the reduced glutathione in the liver of wild-type mice
      under both constitutive and butylated hydroxyanisole-induced conditions. In
      contrast, such distinct responses were not detected in Nrf2(-/-) mice. In
      addition, oral administration of luteolin, either alone or combined with
      intraperitoneal injection of the cytotoxic drug cisplatin, greatly inhibited the
      growth of xenograft tumors from non-small-cell lung cancer (NSCLC) cell line A549
      cells grown subcutaneously in athymic nude mice. Cell proliferation, the
      expression of Nrf2, and antioxidant enzymes were all reduced in tumor xenograft
      tissues. Furthermore, luteolin enhanced the anti-cancer effect of cisplatin.
      Together, our findings demonstrated that luteolin inhibits the Nrf2 pathway in
      vivo and can serve as an adjuvant in the chemotherapy of NSCLC. 

PMID- 24747075
TI  - The fungal chimerolectin MOA inhibits protein and DNA synthesis in NIH/3T3 cells
      and may induce BAX-mediated apoptosis.
AB  - The Marasmius oreades mushroom agglutinin (MOA) is a blood group B-specific
      lectin carrying an active proteolytic domain. Its enzymatic activity has recently
      been shown to be critical for toxicity of MOA toward the fungivorous soil
      nematode Caenorhabditis elegans. Here we present evidence that MOA also induces
      cytotoxicity in a cellular model system (murine NIH/3T3 cells), by inhibiting
      protein synthesis, and that cytotoxicity correlates, at least in part, with
      proteolytic activity. A peptide-array screen identified the apoptosis mediator
      BAX as a potential proteolytic substrate and further suggests a variety of
      bacterial and fungal peptides as potential substrates. These findings are in line
      with the suggestion that MOA and related proteases may play a role for host
      defense. 

PMID- 24747076
TI  - Novel fluorescent protein from Hydnophora rigida possesses green emission.
AB  - Fluorescent proteins are a family of proteins capable of producing fluorescence
      at various specific wavelengths of ultra violet light. We have previously
      reported the identification and characterization of a novel cyan fluorescent
      protein (HriCFP) from a reef coral species, Hydnophora rigida. In search of new
      members of the diverse family of fluorescent proteins, here we report a new green
      fluorescent protein (HriGFP) from H. rigida. HriGFP was identified, cloned,
      expressed in Escherichia coli and purified to homogeneity by metal affinity and
      size exclusion chromatography. The dynamic light scattering and gel filtration
      experiments suggested the presence of monomers in solution. The peptide mass
      fingerprint on the purified protein established the identity of HriGFP. HriGFP
      had excitation peak at 507 nm and emission peak at 527 nm. HriGFP was similar to
      HriCFP except the last 16 amino acid sequence at the C-terminal; however, they
      have shown least similarity with other known fluorescent proteins. Moreover the
      computational model suggests that HriGFP is a globular protein which consists of
      6 alpha-helices and 3 beta-sheets. Taken together our results suggested that
      HriGFP is a novel naturally occurring fluorescent protein that exists as a
      monomer in solution.

PMID- 24747077
TI  - P-glycoprotein mediates the collateral sensitivity of multidrug resistant cells
      to steroid hormones.
AB  - The overexpression of P-glycoprotein (P-gp, ABCB1) in cancer cells often leads to
      multidrug resistance (MDR) through reduced drug accumulation. However, certain P
      gp-positive cells display hypersensitivity, or collateral sensitivity, to certain
      compounds that are believed to induce Pgp-dependent oxidative stress. We have
      previously reported that MDR P-gp-positive CHO cells are collaterally sensitive
      to verapamil (VRP; Laberge et al. (2009) [1]). In this report we extend our
      previous findings and show that drug resistant CHO cells are also collaterally
      sensitive to physiologic levels of progesterone (PRO) and deoxycorticosterone
      (DOC). Both PRO and DOC collateral sensitivities in CH(R)C5 cells are dependent
      on P-gp-expression and ATPase, as knockdown of P-gp expression with siRNA or
      inhibition of P-gp-ATPase with PSC833 reverses PRO- and DOC-induced collateral
      sensitivity. Moreover, the mitochondrial complexes I and III inhibitors
      (antimycin-A and rotenone, respectively) synergize with PRO and DOC-induced
      collateral sensitivity. We also show that VRP inhibits PRO and DOC collateral
      sensitivity, consistent with earlier findings relating to the VRP's modulation of
      PRO and DOC-stimulation of P-gp ATPase. The findings of this study demonstrate a
      P-gp-dependent collateral sensitivity of MDR cells in the presence of
      physiologically achievable concentrations of progesterone and
      deoxycorticosterone. 

PMID- 24747078
TI  - The functional expression and motile properties of recombinant outer arm dynein
      from Tetrahymena.
AB  - Cilia and flagella are motile organelles that play various roles in eukaryotic
      cells. Ciliary movement is driven by axonemal dyneins (outer arm and inner arm
      dyneins) that bind to peripheral microtubule doublets. Elucidating the molecular
      mechanism of ciliary movement requires the genetic engineering of axonemal
      dyneins; however, no expression system for axonemal dyneins has been previously
      established. This study is the first to purify recombinant axonemal dynein with
      motile activity. In the ciliated protozoan Tetrahymena, recombinant outer arm
      dynein purified from ciliary extract was able to slide microtubules in a gliding
      assay. Furthermore, the recombinant dynein moved processively along microtubules
      in a single-molecule motility assay. This expression system will be useful for
      investigating the unique properties of diverse axonemal dyneins and will enable
      future molecular studies on ciliary movement. 

PMID- 24747079
TI  - Potent gamma-secretase inhibitors/modulators interact with amyloid-beta fibrils
      but do not inhibit fibrillation: a high-resolution NMR study.
AB  - Recently, gamma-secretase modulators (GSM) have been shown to interact directly
      with the amyloid precursor protein (APP) and simultaneously inhibit the activity
      of the Presenilin domain of gamma-secretase. A clear understanding of the
      molecular recognition pathways by which GSM can target both gamma-secretase and
      Abeta precursor protein can lead to the development of more effective inhibitors.
      To examine whether this direct interaction with APP affects the downstream Abeta
      fibril formation, we chose to investigate three different molecules in this
      study: Sulindac sulfide, Semagacestat and E2012 from the class of generation I
      GSMs, gamma-secretase inhibitors (GSI), and generation II GSM molecules,
      respectively. Firstly, through NMR based ligand titration, we identified that
      Sulindac sulfide and Semagacestat interact strongly with Abeta40 monomers,
      whereas E2012 does not. Secondly, using saturation transfer difference (STD) NMR
      experiments, we found that all three molecules bind equally well with Abeta40
      fibrils. To determine if these interactions with the monomer/fibril lead to a
      viable inhibition of the fibrillation process, we designed an NMR based time
      dependent assay and accurately distinguished the inhibitors from the non
      inhibitors within a short period of 12h. Based on this pre-seeded fibril assay,
      we conclude that none of these molecules inhibit the ongoing fibrillation, rather
      ligands such as Semagacestat and E2012 accelerated the rate of aggregation. 

PMID- 24747080
TI  - PDGFRbeta and FGFR2 mediate endothelial cell differentiation capability of triple
      negative breast carcinoma cells.
AB  - Triple negative breast cancer (TNBC) is a very aggressive subgroup of breast
      carcinoma, still lacking specific markers for an effective targeted therapy and
      with a poorer prognosis compared to other breast cancer subtypes. In this study
      we investigated the possibility that TNBC cells contribute to the establishment
      of tumor vascular network by the process known as vasculogenic mimicry, through
      endothelial cell differentiation. Vascular-like functional properties of breast
      cancer cell lines were investigated in vitro by tube formation assay and in vivo
      by confocal microscopy, immunofluorescence or immunohistochemistry on frozen
      tumor sections. TNBCs express endothelial markers and acquire the ability to form
      vascular-like channels in vitro and in vivo, both in xenograft models and in
      human specimens, generating blood lacunae surrounded by tumor cells. Notably this
      feature is significantly associated with reduced disease free survival. The
      impairment of the main pathways involved in vessel formation, by treatment with
      inhibitors (i.e. Sunitinib and Bevacizumab) or by siRNA-mediating silencing,
      allowed the identification of PDGFRbeta and FGFR2 as relevant players in this
      phenomenon. Inhibition of these tyrosine kinase receptors negatively affects
      vascular lacunae formation and significantly inhibits TNBC growth in vivo. In
      summary, we demonstrated that TNBCs have the ability to form vascular-like
      channels in vitro and to generate blood lacunae lined by tumor cells in vivo.
      Moreover, this feature is associated with poor outcome, probably contributing to
      the aggressiveness of this breast cancer subgroup. Finally, PDGFRbeta and FGFR2
      mediated pathways, identified as relevant in mediating this characteristic,
      potentially represent valid targets for a specific therapy of this breast cancer
      subgroup.

PMID- 24747081
TI  - Impact of grafting on the design of new membrane adsorbers for adenovirus
      purification.
AB  - The impacts of quaternary amine ligand density and matrix structure, namely
      hydrogel grafted and directly grafted, on state-of-the-art chromatographic
      membranes operated in bind-and-elute mode were evaluated for the purification of
      adenovirus serotype 5. The experiments were performed on a 96-well plate membrane
      holder, which is a convenient high-throughput screening tool for obtaining the
      best operating conditions for a process yield optimization. The results show that
      the hydrogel-grafted membranes are more suitable for virus purification than the
      directly grafted ones. By reducing the number of grafted ligands to low
      (1.7MUmol/cm(2)) or medium (2.4MUmol/cm(2)) density, it is possible to increase
      the recovery of purified virus by 60% compared to a highly charged membrane
      (3.3MUmol/cm(2)) that yielded a recovery rate lower than 30%. In the reported
      experiments, Sartobind((r)) Q, chosen as benchmark comparison, provides a better
      compromise between high recovery and large dynamic binding capacity. Overall,
      this work contributes to the understanding and development of new membrane
      adsorbers specifically designed for virus purification. 

PMID- 24747082
TI  - Lead toxicity on non-specific immune mechanisms of freshwater fish Channa
      punctatus.
AB  - Lead has no known role in the body that is physiologically relevant, and its
      harmful effects are myriad. Lead from the atmosphere and soil ends up in water
      bodies thus affecting the aquatic organisms. This situation has thus prompted
      numerous investigations on the effects of this metal on the biological functions
      of aquatic organisms, particularly on immune mechanisms in fish. This paper
      addresses the immunotoxicologic effects of lead acetate in intestinal macrophages
      of freshwater fish Channa punctatus. Fish were exposed to lead acetate (9.43mg/l)
      for 4 days. When checked for its effects on macrophages, it was noted that lead
      interfered with bacterial phagocytosis, intracellular killing capacity and cell
      adhesion as well as inhibited release of antimicrobial substances like nitric
      oxide (NO) and myeloperoxidase (MPO). On giving bacterial challenge with
      Staphylococcus aureus to intestinal macrophages of both control and lead treated
      groups, the macrophages showed significantly higher concentration of viable
      bacteria in the intracellular milieu in lead treated group as compared to
      control. We also report that in vivo exposure to lead acetate inhibits
      phagocytosis, which is evident from a reduced phagocytic index of treated group
      from that of the control. The amount of MPO and NO released by the control cells
      was also reduced significantly upon in vivo lead treatment. The property of
      antigenic adherence to the macrophage cell membrane, a vital process in
      phagocytosis, was significantly decreased in the treated group as compared to
      control. Severe damage in intestinal epithelium, disarrangement and fragmentation
      of mucosal foldings was observed in lead treated group when compared with the
      untreated group. The present results also showed decreased tumor necrosis factor
      alpha (TNF-alpha) level upon metal exposure in sera as well as cell lysate of
      lead exposed fish thus, implicating both MAPK signaling pathways as well as
      NFkappabeta signaling. We thus conclude that lead affects the general immune
      status of C. punctatus and renders the fish immunocompromised and susceptible to
      pathogens. 

PMID- 24747083
TI  - Modulation of estrogen causes disruption of craniofacial chondrogenesis in Danio
      rerio.
AB  - Estrogen is a steroid hormone that is ubiquitous in vertebrates, but its role in
      cartilage formation has not been extensively studied. Abnormalities of
      craniofacial cartilage and bone account for a large portion of birth defects in
      the United States. Zebrafish (Danio rerio) have been used as models of human
      disease, and their transparency in the embryonic period affords additional
      advantages in studying craniofacial development. In this study, zebrafish embryos
      were treated with 17-beta estradiol (E2) or with an aromatase inhibitor and
      observed for defects in craniofacial cartilage. Concentrations of E2 greater than
      2MUM caused major disruptions in cartilage formation. Concentrations below 2MUM
      caused subtle changed in cartilage morphology that were only revealed by
      measurement. The angles formed by cartilage elements in fish treated with 1.5 and
      2MUM E2 were increasingly wide, while the length of the primary anterior
      posterior cartilage element in these fish decreased significantly from controls.
      These treatments resulted in fish with shorter, flatter faces as estrogen
      concentration increased. Inhibition of aromatase activity also resulted in
      similar craniofacial disruption indicating that careful control of estrogen
      signaling is required for appropriate development. Further investigation of the
      phenomena described in this study could lead to a better understanding of the
      etiology of craniofacial birth defects and endocrine disruption of cartilage
      formation. 

PMID- 24747084
TI  - Influence of agglomeration of cerium oxide nanoparticles and speciation of
      cerium(III) on short term effects to the green algae Chlamydomonas reinhardtii.
AB  - Cerium oxide nanoparticles (CeO2 NP) are increasingly used in industrial
      applications and may be released to the aquatic environment. The fate of CeO2 NP
      and effects on algae are largely unknown. In this study, the short term effects
      of CeO2 NP in two different agglomeration states on the green algae Chlamydomonas
      reinhardtii were examined. The role of dissolved cerium(III) on toxicity, its
      speciation and the dissolution of CeO2 NP were considered. The role of cell wall
      of C. reinhardtii as a barrier and its influence on the sensitivity to CeO2 NP
      and cerium(III) was evaluated by testing both, the wild type and the cell wall
      free mutant of C. reinhardtii. Characterization showed that CeO2 NP had a surface
      charge of ~0mV at physiological pH and agglomerated in exposure media. Phosphate
      stabilized CeO2 NP at pH 7.5 over 24h. This effect was exploited to test CeO2 NP
      dispersed in phosphate with a mean size of 140nm and agglomerated in absence of
      phosphate with a mean size of 2000nm. The level of dissolved cerium(III) in CeO2
      NP suspensions was very low and between 0.1 and 27nM in all tested media.
      Exposure of C. reinhardtii to Ce(NO3)3 decreased the photosynthetic yield in a
      concentration dependent manner with EC50 of 7.5+/-0.84MUM for wild type and EC50
      of 6.3+/-0.53MUM for the cell wall free mutant. The intracellular level of
      reactive oxygen species (ROS) increased upon exposure to Ce(NO3)3 with effective
      concentrations similar to those inhibiting photosynthesis. The agglomerated CeO2
      NP caused a slight decrease of photosynthetic yield at the highest concentrations
      (100MUM), while no effect was observed for dispersed CeO2 NP. The low toxicity of
      agglomerated CeO2 NP was attributed quantitatively to Ce(3+) ions co-occurring in
      the nanoparticle suspension whereas for dispersed CeO2 NP, dissolved Ce(3+) was
      precipitated with phosphate and not bioavailable. Furthermore CeO2 NP did not
      affect the intracellular ROS level. The cell wall free mutant and wild type of C.
      reinhardtii showed the same sensitivity to CeO2 NP and Ce(NO3)3, indicating a
      minor role of the cell wall on toxicity. For both algae strains, a flocculation
      of cells was observed upon exposure to agglomerated CeO2 NP and Ce(NO3)3, only
      algae exposed to agglomerated CeO2 NP were tightly packed in exopolymeric
      substances. 

PMID- 24747085
TI  - MicroRNA miR-513a-3p acts as a co-regulator of luteinizing hormone/chorionic
      gonadotropin receptor gene expression in human granulosa cells.
AB  - The luteinizing hormone/chorionic gonadotropin receptor (LHCGR) is essential for
      normal male and female reproductive processes. The spatial and temporal LHCGR
      gene expression is controlled by a complex system of regulatory mechanisms which
      are crucial for normal physiological function, especially during the female
      cycle. In this study, we aimed to elucidate whether microRNAs are involved in
      this network and play a role in regulating LHCGR expression. Computational
      analysis predicted that miR-513a-3p interacts with the LHCGR mRNA via three
      binding sites located in the 3'UTR region, enabling a synergistic action.
      Moreover, using a luciferase-based reporter assay we found that miR-513a-3p
      targets the LHCGR, resulting in a significant down-regulation of its expression.
      In human primary granulosa cell cultures we detected a dynamic, inversely
      associated expression pattern of miR-513a-3p and the LHCGR. In addition,
      transfection with miR-513a-3p or its specific inhibitor led to a down- or up
      regulation at the LHCGR mRNA level, respectively. An increased amount of miR-513a
      3p resulted in the down-regulation of the LHCGR mRNA, reflected by the
      attenuation of cAMP synthesis after hormonal stimulation. In conclusion, these
      data demonstrate that miR-513a-3p is involved in the control of the LHCGR
      expression by an inversely regulated mechanism at the post-transcriptional level
      and show for the first time that this kind of post-transcriptional process
      contributes to the multifaceted system of the human LHCGR regulation.

PMID- 24747086
TI  - pH- and thermosensitive thin lipid layer coated mesoporous magnetic
      nanoassemblies as a dual drug delivery system towards thermochemotherapy of
      cancer.
AB  - A new pH-sensitive and thermosensitive dual drug delivery system consisting of
      thin lipid layer encapsulated mesoporous magnetite nanoassemblies (MMNA) has been
      developed which can deliver two anticancer drugs simultaneously. The formulation
      of lipid layer used is 5:2:2:2 w/w, DPPC:cholesterol:DSPE-PEG2000:MMNA. The
      structure, morphology and magnetic properties of MMNA and lipid coated MMNA
      (LMMNA) were thoroughly characterized. This hybrid system was investigated for
      its ability to carry two anticancer drugs as well as its ability to provide heat
      under an alternating current magnetic field (ACMF). A very high loading
      efficiency of up to ~81% of doxorubicin hydrochloride (DOX) with an ~0.02 mg mg(
      1) loading capacity and ~60% of paclitaxel (TXL) with an ~0.03 mg mg(-1) loading
      capacity are obtained with LMMNA. A sustained release of drug is observed over a
      period of 172 h, with better release, of ~88:53% (DOX:TXL), at pH 4.3 compared to
      the ~28:26% (DOX:TXL) in physiological conditions (pH 7.4). An enhanced release
      of ~72 and ~68% is recorded for DOX and TXL, respectively, during the first hour
      with the application of an ACMF (~43 degrees C). A greater in vitro cytotoxic
      effect is observed with the two drugs compared to them individually in HeLa, MCF
      7 and HepG2 cancer cells. With the application of an ACMF for 10 min, the cell
      killing efficiency is improved substantially due to simultaneous thermo- and
      chemotherapy. Confocal microscopy confirms the internalization of drug loaded
      MMNA and LMMNA by cells and their morphological changes during
      thermochemotherapy.

PMID- 24747087
TI  - A statistically motivated framework for simulation of stochastic data fusion
      models applied to multimodal neuroimaging.
AB  - Multimodal fusion is becoming more common as it proves to be a powerful approach
      to identify complementary information from multimodal datasets. However,
      simulation of joint information is not straightforward. Published approaches
      mostly employ limited, provisional designs that often break the link between the
      model assumptions and the data for the sake of demonstrating properties of fusion
      techniques. This work introduces a new approach to synthetic data generation
      which allows full-compliance between data and model while still representing
      realistic spatiotemporal features in accordance with the current neuroimaging
      literature. The focus is on the simulation of joint information for the
      verification of stochastic linear models, particularly those used in multimodal
      data fusion of brain imaging data. Our first goal is to obtain a benchmark ground
      truth in which estimation errors due to model mismatch are minimal or none. Then
      we move on to assess how estimation is affected by gradually increasing model
      discrepancies toward a more realistic dataset. The key aspect of our approach is
      that it permits complete control over the type and level of model mismatch,
      allowing for more educated inferences about the limitations and caveats of select
      stochastic linear models. As a result, impartial comparison of models is possible
      based on their performance in multiple different scenarios. Our proposed method
      uses the commonly overlooked theory of copulas to enable full control of the type
      and level of dependence/association between modalities, with no occurrence of
      spurious multimodal associations. Moreover, our approach allows for arbitrary
      single-modality marginal distributions for any fixed choice of
      dependence/association between multimodal features. Using our simulation
      framework, we can rigorously challenge the assumptions of several existing
      multimodal fusion approaches. Our study brings a new perspective to the problem
      of simulating multimodal data that can be used for ground-truth verification of
      various stochastic multimodal models available in the literature, and reveals
      some important aspects that are not captured or are overlooked by ad hoc
      simulations that lack a firm statistical motivation. 

PMID- 24747088
TI  - An outbreak of aseptic meningitis caused by a distinct lineage of coxsackievirus
      B5 in China.
AB  - In 2009, an outbreak of aseptic meningitis caused by coxsackievirus B5 (CVB5)
      occurred in China. Epidemiological investigations of this outbreak revealed that
      the proportion of severe cases (14/43, 33%) was higher than in other outbreaks
      associated with CVB5 in China. Phylogenetic analysis of the entire VP1 sequences
      demonstrated that the CVB5 isolates from the severe cases form a distinct lineage
      belonging to genogroup E with the Shandong isolates of 2009. A substitution of
      serine (S) to asparagine (N) at amino acid 95 in the VP1 region may be a major
      virulence determinant for the virus. Our findings suggest that this new lineage
      of CVB5 is circulating in China. Further genetic studies are needed in order to
      gain a better insight into the genetic variability of CVB5 isolates and the
      relationship with pathogenicity. 

PMID- 24747089
TI  - World review of laparoscopic treatment of liver cystic echinococcosis--914
      patients.
AB  - OBJECTIVE: The aim of this study was to provide a review of the world literature
      on the laparoscopic treatment of liver hydatid cyst. METHODS: We conducted a
      literature search using PubMed, screening all English language publications on
      the laparoscopic treatment of liver hydatid cysts. Operative characteristics,
      perioperative morbidity, and clinical outcomes were tabulated. RESULTS: A total
      of 57 published articles including 914 patients with 1116 hydatid cysts were
      identified. Of the resections done in the 914 patients, 89.17% were performed
      totally laparoscopically and 5.58% were gasless. The most common procedure was
      cystectomy (60.39%), followed by partial pericystectomy (14.77%) and
      pericystectomy (8.21%); the rest were segmentectomies. Conversion to open
      laparotomy occurred in 4.92% of reported cases (45/914). The common cause of
      conversion was anatomical limitations/inaccessible locations (16/45). The overall
      mortality was 0.22% (2/914 patients) and morbidity was 15.07%, with no
      intraoperative deaths reported. The most common complication was bile leakage
      (57/914). The postoperative recurrence was 1.09% (10/914 patients). CONCLUSIONS:
      The laparoscopic approach is safe with acceptable mortality and morbidity for
      both conservative and radical resections in selected patients. Clinical outcomes
      are comparable to open surgery, albeit in a selected group of patients.

PMID- 24747090
TI  - Is there a role for body mass index in the assessment of prostate cancer risk on
      biopsy?
AB  - PURPOSE: We examine the role of body mass index in the assessment of prostate
      cancer risk. MATERIALS AND METHODS: A total of 3,258 participants who underwent
      biopsy (including 1,902 men with a diagnosis of prostate cancer) were identified
      from the Selenium and Vitamin E Cancer Prevention Trial. The associations of body
      mass index with prostate cancer and high grade prostate cancer were examined
      using logistic regression, adjusting for age, race, body mass index adjusted
      prostate specific antigen, digital rectal examination, family history of prostate
      cancer, biopsy history, prostate specific antigen velocity, and time between
      study entry and the last biopsy. The prediction models were compared with our
      previously developed body mass index adjusted Prostate Cancer Prevention Trial
      prostate cancer risk calculator. RESULTS: Of the study subjects 49.1% were
      overweight and 29.3% were obese. After adjustment, among men without a known
      family history of prostate cancer, increased body mass index was not associated
      with a higher risk of prostate cancer (per one-unit increase in logBMI OR 0.83,
      p=0.54) but was significantly associated with a higher risk of high grade
      prostate cancer (ie Gleason score 7 or greater prostate cancer) (OR 2.31,
      p=0.03). For men with a known family history of prostate cancer the risks of
      prostate cancer and high grade prostate cancer increased rapidly as body mass
      index increased (prostate cancer OR 3.73, p=0.02; high grade prostate cancer OR
      7.95, p=0.002). The previously developed risk calculator generally underestimated
      the risks of prostate cancer and high grade prostate cancer. CONCLUSIONS: Body
      mass index provided independently predictive information regarding the risks of
      prostate cancer and high grade prostate cancer after adjusting for other risk
      factors. Body mass index, especially in men with a known family history of
      prostate cancer, should be considered for inclusion in any clinical assessment of
      prostate cancer risk and recommendations regarding prostate biopsy.

PMID- 24747092
TI  - Quality of life for patients treated for penile cancer.
AB  - PURPOSE: We assessed the impact of primary surgery, including penile sparing
      surgery vs (partial) penectomy and lymphadenectomy, on sexuality and health
      related quality of life. MATERIALS AND METHODS: We invited 147 patients
      surgically treated for penile cancer at our institution between 2003 and 2008 to
      complete the IIEF-15, SF-36(r), IOC (version 2) and questions on urinary
      function. We evaluated the impact of primary surgery type and lymphadenectomy on
      these outcomes. We also compared patient SF-36 scores with those of an age and
      gender matched normative sample from the general Dutch population. RESULTS: A
      total of 90 patients (62%) returned a completed questionnaire. Surgery type and
      extent were not associated significantly with most of the study outcomes
      assessed. However, men who underwent (partial) penectomy reported significantly
      more problems than those treated with penile sparing surgery, including orgasm
      (effect size 0.54, p = 0.031), appearance concerns (effect size 0.61, p = 0.008),
      life interference (effect size 0.49, p = 0.032) and urinary function (83% vs 43%,
      p <0.0001). Men who underwent lymphadenectomy reported significantly more life
      interference (effect size 0.50, p = 0.037). The patient sample scored
      significantly better than the normative sample on the SF-36 physical component (p
      = 0.044) and the bodily pain subscale (p <0.001). CONCLUSIONS: Few differences
      were observed in sexuality and health related quality of life as a function of
      primary surgery and lymphadenectomy. However, (partial) penectomy and
      lymphadenectomy were associated with more problems with orgasm, body image, life
      interference and urination. Additional longitudinal studies are warranted to
      evaluate individual changes with time in these outcomes.

PMID- 24747091
TI  - High prevalence of screen detected prostate cancer in West Africans: implications
      for racial disparity of prostate cancer.
AB  - PURPOSE: To our knowledge the reasons for the high rates of prostate cancer in
      black American men are unknown. Genetic and lifestyle factors have been
      implicated. Better understanding of prostate cancer rates in West African men
      would help clarify why black American men have such high rates since the groups
      share genetic ancestry and yet have different lifestyles and screening practices.
      To estimate the prostate cancer burden in West African men we performed a
      population based screening study with biopsy confirmation in Ghana. MATERIALS AND
      METHODS: We randomly selected 1,037 healthy men 50 to 74 years old from Accra,
      Ghana for prostate cancer screening with prostate specific antigen testing and
      digital rectal examination. Men with a positive screen result (positive digital
      rectal examination or prostate specific antigen greater than 2.5 ng/ml) underwent
      transrectal ultrasound guided biopsies. RESULTS: Of the 1,037 men 154 (14.9%) had
      a positive digital rectal examination and 272 (26.2%) had prostate specific
      antigen greater than 2.5 ng/ml, including 166 with prostate specific antigen
      greater than 4.0 ng/ml. A total of 352 men (33.9%) had a positive screen by
      prostate specific antigen or digital rectal examination and 307 (87%) underwent
      biopsy. Of these men 73 were confirmed to have prostate cancer, yielding a 7.0%
      screen detected prostate cancer prevalence (65 patients), including 5.8% with
      prostate specific antigen greater than 4.0 ng/ml. CONCLUSIONS: In this relatively
      unscreened population in Africa the screen detected prostate cancer prevalence is
      high, suggesting a possible role of genetics in prostate cancer etiology and the
      disparity in prostate cancer risk between black and white American men. Further
      studies are needed to confirm the high prostate cancer burden in African men and
      the role of genetics in prostate cancer etiology.

PMID- 24747093
TI  - Mortality risk after stent post-dilation.

PMID- 24747094
TI  - Daphnetin attenuates microglial activation and proinflammatory factor production
      via multiple signaling pathways.
AB  - Daphnetin, a natural coumarin derivative, is known to display anti-inflammatory
      properties and has been used to treat inflammatory diseases. A novel finding
      suggested that daphnetin might have a neuroprotective effect in stressed mice,
      leading us to explore its role in the microglial inflammatory response, as well
      as its underlying mechanism of action. We found that the production of pro
      inflammatory mediators, including interleukin-1beta (IL-1beta) and tumor necrosis
      factor-alpha (TNF-alpha), induced by lipopolysaccharide (LPS) or beta-amyloid
      (Abeta) was significantly suppressed by daphnetin in a dose-dependent manner in
      BV2 microglia. Also, daphnetin inhibited LPS-induced nitric oxide synthase (iNOS)
      and cyclooxygenase-2 (COX-2) expression and NO formation by microglia.
      Mechanistically, daphnetin blunted the transcriptional activity of nuclear factor
      kappa B (NF-kappaB), which was associated with the down-regulation of the
      phosphorylation and nuclear translocation of RelA/p65. Inhibitors of kappa B
      (IkappaB) phosphorylation and degradation were also affected by daphnetin, which
      was likely due to the reduced activation of IkappaB kinase (IKK). Additionally,
      LPS-induced activation of mitogen-activated protein kinases (MAPKs), such as
      extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK) and
      p38 MAPK, were, to a varying extent, altered by daphnetin. Finally, daphnetin
      blocked phosphatidylinositol-3 kinase (PI-3K)/protein kinase B (Akt) signaling in
      LPS-activated microglia, which appeared to at least partially account for the
      reduction in NF-kappaB transcriptional activity. Thus, daphnetin inhibited
      microglial activation and proinflammatory responses by modulating a series of
      intracellular signaling pathways, including IKK/IkappaB, MAPKs and PI-3K/Akt. 

PMID- 24747095
TI  - Effects of high-dose intravenous immunoglobulin on lipopolysaccharide-induced
      acute lung injury.
AB  - PURPOSE: Intravenous immunoglobulin (IVIG) therapy is used in inflammatory
      diseases but the use of immunoglobulin as a treatment for acute lung injury (ALI)
      has not been previously studied. Transforming growth factor beta (TGF-beta) plays
      a critical role in the pathogenesis of of ALI. Therefore we examined the levels
      of TGF-beta and lung inflammation scores in IVIG treated ALI models. METHODS:
      Intratracheal lipopolysacccharide was given to rats. Groups 1 and 3 received
      saline, whereas group 2 received IVIG. 24h later saline was given to groups 1 and
      2 and IVIG to group 3. Blood samples and bronchoalveolar lavage (BAL) fluids were
      obtained from each group and sacrificed for pathological evaluation. RESULTS: BAL
      TGF-beta levels of groups 2 and 3 on day 30, were lower compared to their levels
      of day 2 (p=0.01, p=0.01). BAL TGF-beta levels of groups 2 and 3 were lower than
      the levels of group 1 on day 30 (p=0.002, p=0.001). Pathological examination
      revealed that the inflammation scores of groups 2 and 3 on day 30, were lower
      than the scores of day 2 (p=0.02, p=0.01). Inflammation scores of group 2 were
      lower than group 1 on day 30 (p=0.02). Moderate fibrosis was seen in half of the
      rats from group 1 and one rat from group 2. CONCLUSION: High-dose IVIG decreased
      lung inflammation scores and BAL TGF-beta1 levels and this therapy would give
      even better results if it is given earlier.

PMID- 24747096
TI  - Resin composite characterizations following a simplified protocol of accelerated
      aging as a function of the expiration date.
AB  - This study evaluated the mechanical, thermal, and morphological characteristics
      of different classifications of dental composites as a function of the material
      condition (new, aged and expired). Specimens were obtained according to these
      factors: Composites: Filtek P60, Filtek Z250, Filtek Z350XT, and Filtek Silorane;
      and Material conditions: new, aged, and expired. The syringe composites underwent
      an accelerated aging protocol (Arrhenius model). The flexural strength (FS) and
      flexural modulus (E) were obtained. The thermogravimetric analysis (TGA) and
      differential thermal analysis (DTA) were also performed and the glass transition
      temperature (Tg) and the weight loss calculated. Topographic analysis of the
      composites was performed under SEM. The material conditions influenced the
      mechanical properties of the composites. The silorane composite exhibited a
      characteristic thermal behavior different from that of the methacrylates. In
      general, the Tg increased after the accelerated aging protocol and decreased for
      expired ones, compared to the new composites. A significant increase in FS of
      Filtek Z350XT after aging was accompanied by an increase in the Tg. The filler
      packings were in accordance with the manufacture's information. The topographic
      aspects of the composites were modified as a function of the material condition.
      The mechanical properties of the composites following a simplified protocol of
      accelerated aging varied as a function of the expiration date. The silorane
      composite presented a characteristic thermal behavior. Although the dental
      manufacturers may not be able to control variables as storage temperature and
      transportation conditions, these effects on the composite clinical performance
      can be minimized if properly considered. 

PMID- 24747097
TI  - Preparation and evaluation of cerium oxide-bovine hydroxyapatite composites for
      biomedical engineering applications.
AB  - The fabrication and characterization of bovine hydroxyapatite (BHA) and cerium
      oxide (CeO2) composites are presented. CeO2 (at varying concentrations 1, 5 and
      10wt%) were added to calcinated BHA powder. The resulting mixtures were shaped
      into green cylindrical samples by powder pressing (350MPa) followed by sintering
      in air (1000-1300 degrees C for 4h). Density, Vickers microhardness (HV),
      compression strength, scanning electron microscopy (SEM) and X-ray diffraction
      (XRD) studies were performed on the products. The sintering behavior,
      microstructural characteristics and mechanical properties were evaluated.
      Differences in the sintering temperature (for 1wt% CeO2 composites) between 1200
      and 1300 degrees C, show a 3.3% increase in the microhardness (564 and 582.75HV,
      respectively). Composites prepared at 1300 degrees C demonstrate the greatest
      compression strength with comparable results for 5 and 10wt% CeO2 content (106
      and 107MPa) which are significantly better than those for 1wt% and those that do
      not include any CeO2 (90 and below 60MPa, respectively). The results obtained
      suggest optimal parameters to be used in preparation of BHA and CeO2 composites,
      while also highlighting the potential of such materials in several biomedical
      engineering applications. 

PMID- 24747098
TI  - Failure modes and fracture toughness in partially torn ligaments and tendons.
AB  - Ligaments and tendons are commonly torn during injury, yet the likelihood that
      untreated initial tears could lead to further tearing or even full rupture has
      proven challenging to predict. In this work, porcine Achilles tendon and human
      anterior longitudinal ligament samples were tested using both standard fracture
      toughness methods and complex loading conditions. Failure modes for each of 14
      distinct testing cases were evaluated using a total of 131 soft tissue tests.
      Results showed that these soft tissues were able to completely resist any further
      crack propagation of an initial tear, regardless of fiber orientation or applied
      loading condition. Consequently, the major concern for patients with tendon or
      ligament tears is likely not reduction in ultimate tissue strength due to stress
      risers at the tip of the tear, but rather a question of whether or not the
      remaining cross-section is large enough to support the anticipated loading. 

PMID- 24747099
TI  - A novel implantation technique for pudendal nerve stimulation for treatment of
      overactive bladder and urgency incontinence.
AB  - Herein is described laparoscopic implantation of a neuroprosthesis to the
      pudendal nerve for treatment of non-neurogenic bladder overactivity. This case
      series study was performed at a tertiary referral unit that specializes in
      advanced gynecologic surgery and neuropelveology. Fourteen consecutive male and
      female patients underwent laparoscopic implantation of an electrode to the
      endopelvic portion of the pudendal nerve for pudendal neuromodulation. All
      procedures were performed successfully via laparoscopy, without any
      complications. The mean operative time for the entire procedure was 18 minutes.
      After a successful test phase of external stimulation, 11 patients (78.57%)
      underwent implantation of a permanent generator. These patients demonstrated a
      mean (SD) decreased micturition frequency, from 25 (11.7; range, 13-50) per day
      on average to 10.18 (2.7; range, 7-15) at final evaluation (mean follow-up, 18
      months; range 9-49 months). Nocturia decreased from 5.82 (4.2; range, 3-18) to
      2.18 (1.08; range, 1-5) micturitions per night. Cystometric bladder capacities
      increased from 159 mL (53; range, 80-230 mL) to 312 mL (104.9;160-500 mL). Mean
      incontinence episodes at the initial evaluation, based on a 3-day voiding diary,
      were 8.1. At final evaluation, 6 patients were completely dry. Number of pads
      used per day decreased from 7.3 (4.2) to 1.6 (2.3). No lead dislocation or
      migration occurred. It was concluded that laparoscopic implantation of a
      neuroprosthesis to the pudendal nerve is an effective, safe, and reproducible day
      procedure for treatment of intractable non-neurogenic overactive bladder with
      urinary urgency incontinence.

PMID- 24747100
TI  - Unexpected deviation in circadian variation of ventricular arrhythmias: the SCD
      HeFT (Sudden Cardiac Death in Heart Failure Trial).
AB  - OBJECTIVES: This study sought to determine whether circadian patterns in
      ventricular arrhythmias (VAs) occur in a current primary prevention defibrillator
      (implantable cardioverter-defibrillator [ICD]) population. BACKGROUND:
      Cardiovascular events, including VAs, demonstrate biorhythmic periodicity.
      METHODS: We tested for deviation from the previously described occurrences of a
      morning peak, early morning nadir, and peak on Mondays in ICD therapies using
      generalized estimating equations and Student t tests. All hypothesis tests were
      performed in the entire cohort of patients with VAs as well as pre-specified
      subgroups. RESULTS: Of 811 patients with an ICD, 186 subjects experienced 714 ICD
      therapy episodes for life-threatening VA. There was no morning (6 am to 12 pm)
      peak in therapies for the entire cohort or any subgroups. The overall cohort and
      several subgroups had a typical early morning (12 am to 6 am) nadir in therapies,
      with significantly less than 25% of therapies occurring during this 6-h block
      (all p < 0.05). A significant peak in therapies on Mondays occurred only in
      patients not on beta-blocker therapy (22% of events for the week, p = 0.029).
      CONCLUSIONS: In the SCD-HeFT (Sudden Cardiac Death in Heart Failure Trial)
      population, the distribution of life-threatening VA failed to show a typical
      early morning peak or increased VA events on Mondays. A typical early morning
      nadir was seen in the entire cohort. An increased rate of events on Mondays was
      found in the subgroup of subjects not on beta-blocker therapy. These findings may
      indicate suppression of the neurohormonal triggers for VA by current heart
      failure therapy, particularly the use of beta-blockers in heart failure.

PMID- 24747101
TI  - Impact of sex on morbidity and mortality rates after lower extremity
      interventions for peripheral arterial disease: observations from the Blue Cross
      Blue Shield of Michigan Cardiovascular Consortium.
AB  - OBJECTIVES: This study sought to examine sex-related differences in outcomes
      related to peripheral vascular intervention (PVI) procedures. BACKGROUND:
      Percutaneous PVI is frequently performed for the treatment of peripheral arterial
      disease (PAD). However, little is known about sex-related differences related to
      PVI procedures. METHODS: We assessed the impact of sex among 12,379 patients (41%
      female) who underwent lower extremity (LE)-PVI from 2004 to 2009 at 16 hospitals
      participating in the Blue Cross Blue Shield of Michigan Cardiovascular Consortium
      PVI registry. Multivariate propensity-matched analyses were performed to adjust
      for differences in baseline characteristics, procedural indications, and
      comorbidities on the basis of sex. RESULTS: Compared with men, women were older
      and have multilevel disease and critical limb ischemia. In a propensity-matched
      analysis, female sex was associated with a higher rate of vascular complications,
      transfusions, and embolism. No differences were observed for in-hospital death,
      myocardial infarction, or stroke or transient ischemic attack. Technical success
      was more commonly achieved in women (91.2% vs. 89.1%, p = 0.014), but because of
      a higher complication rate, the overall procedural success rates were similar in
      men and women (79.7% vs. 81.6%, p = 0.08). CONCLUSIONS: Women represent a
      significant proportion of patients undergoing LE-PVI, have a more severe and
      complex disease process, and are at increased risk for adverse outcomes. Despite
      higher complications rates, women had similar procedural success compared with
      men, making PVI an effective treatment strategy among women with LE-PAD.

PMID- 24747102
TI  - Elevation of cardiac troponin T, but not cardiac troponin I, in patients with
      neuromuscular diseases: implications for the diagnosis of myocardial infarction.
AB  - OBJECTIVES: This study sought to determine the clinical and biological
      significance of elevated cardiac troponin T (cTnT) in patients with neuromuscular
      diseases. BACKGROUND: Practice guidelines regard cTnT and cardiac troponin I
      (cTnI) as equally sensitive and specific for the diagnosis of myocardial injury.
      Although cTnI is unique to myocardium, cTnT can be re-expressed in skeletal
      muscle in response to injury. The commercial cTnT assay is claimed to be cardiac
      specific. METHODS: Fifty-two patients with 20 different types of acquired and
      inherited neuromuscular diseases underwent full clinical assessment, cardiac
      investigations, and measurements of serum cTnT, cTnI, creatine kinase (CK),
      creatine kinase myocardial band (CK-MB), and N-terminal pro-B-type natriuretic
      peptide (NT-proBNP). RESULTS: Serial measurements (265 samples) in 25 initially
      hospitalized patients taken during a mean of 2.4 years showed persistent
      elevation of cTnT (median: 0.08 MUg/l; interquartile range: 0.06 to 0.14 MUg/l),
      CK (582 U/l; 303 to 3,662 U/l), and CK-MB (24 MUg/l; 8 to 34 MUg/l). In contrast,
      cTnI, measured using 2 sensitive assays, was persistently normal throughout the
      study in 22 patients. Electrocardiograms (ECGs) and echocardiograms were normal
      in 16 and 17 patients, respectively, and no serial changes were observed.
      Therapeutic interventions in patients with reversible myopathies normalized cTnT,
      CK, and CK-MB in unison. Single measurements in 27 ambulatory patients showed
      elevated CK (953 U/l; 562 to 1,320 U/l), CK-MB (18 MUg/l; 11 to 28 MUg/l), and
      cTnT (0.03 MUg/l; 0.02 to 0.05 MUg/l) in 21, 22, and 18 patients respectively.
      cTnI was abnormal in only 1 patient. NT-proBNP (41 pg/ml; 35 to 97 pg/ml) was
      normal in all but 2 patients. ECGs were normal in 15 patients. No patients with
      elevated cTnT, but with normal cTnI, had any cardiovascular events in either
      group during follow-up. CONCLUSIONS: Patients with a wide spectrum of
      neuromuscular diseases commonly have persistent elevation of cTnT and CK-MB in
      the absence of clinical and cTnI evidence of myocardial injury. Re-expressed cTnT
      in diseased skeletal muscle appears to be the source of the elevated cTnT
      detected in the circulation of these patients.

PMID- 24747103
TI  - Biological clocks and ventricular tachyarrhythmias.

PMID- 24747104
TI  - Allometric relationships to liver tissue concentrations of cyclic volatile methyl
      siloxanes in Atlantic cod.
AB  - Spatial distribution and relationship of allometric measurements (length, weight
      and age) to liver concentrations of cyclic volatile methyl siloxanes (cVMS)
      including octamethylcyclotetrasiloxane (D4), decamethylcyclopentasiloxane (D5)
      and dodecamethylcyclosiloxane (D6) in Atlantic cod (Gadus morhua) collected near
      the community of Tromso in Northern Norway were assessed. These congeners were
      benchmarked against known persistent polychlorinated biphenyls (PCBs 153 and 180)
      to assess accumulation behavior of cVMS. D5 was the dominate cVMS detected in all
      fish livers with lipid normalized concentrations up to 10 times or greater than
      those observed for PCB 153 and 180. D4 and D6 concentration were negatively
      correlated with fish length and weight, indicating a greater elimination capacity
      compared to uptake processes with increasing fish size for these chemicals. These
      results indicate relationships between allometric measurements and cVMS
      concentrations may account for concentration variations observed within fish and
      should be assessed in future studies evaluating cVMS bioaccumulation potential. 

PMID- 24747105
TI  - Occurrence and transport of 17 perfluoroalkyl acids in 12 coastal rivers in south
      Bohai coastal region of China with concentrated fluoropolymer facilities.
AB  - Perfluoroalkyl acids (PFAAs) are emerging contaminants that have raised great
      concern in recent years. While PFAAs manufacturing becomes regulated in developed
      countries, production has been partly shifted to China. Eight fluoropolymer
      manufacturing facilities located in the South Bohai coastal region, one of the
      most populated areas of China, have been used to manufacture PFAA-related
      substances since 2001. The environmental consequence of the intensive production
      of PFAAs in this region remains largely unknown. We analyzed 17 PFAAs in twelve
      coastal rivers of this region, and found staggeringly high concentrations of
      perfluorooctanoic acid (PFOA) ranging from 0.96 to 4534.41 ng/L. The highest
      concentration was observed in the Xiaoqing River which received effluents from
      certain fluoropolymer facilities. Principal component analysis indicated similar
      sources of several perfluoroalkyl carboxylic acids (PFCAs) in all rivers, which
      indicated that atmospheric transport, wastewater treatment and surface runoff
      also acted as important supplements to direct discharge to surface water. 

PMID- 24747106
TI  - Toxicokinetics of metals in the earthworm Lumbricus rubellus exposed to natural
      polluted soils--relevance of laboratory tests to the field situation.
AB  - The aim of this study was to estimate the bioavailability of essential (Zn, Cu)
      and non-essential metals (Cd, Pb) to the earthworm Lumbricus rubellus exposed to
      soils originating from a gradient of metal pollution in Southern Poland. Metal
      uptake and elimination kinetics were determined and related to soils properties.
      Experimental results were compared with tissue metal concentrations observed in
      earthworms from the studied transect. Cd and Pb were intensively accumulated by
      the earthworms, with very slow or no elimination. Their uptake rate constants,
      based on 0.01 M CaCl2-extractable concentrations in the soils, increased with
      soil pH. Internal concentrations of Cu and Zn were maintained by the earthworms
      at a stable level, suggesting efficient regulation of these metals by the
      animals. The estimated uptake and elimination kinetics parameters enabled fairly
      accurate prediction of metal concentrations reached within a life span of L.
      rubellus in nature. 

PMID- 24747107
TI  - Clinical implications of elevated HIV-1 viral load results obtained from samples
      stored frozen in vacutainer plasma preparation tubes.
AB  - Studies have demonstrated that plasma samples collected and stored frozen using
      vacutainer plasma preparation tubes (PPT) may result in falsely elevated viral
      load (VL) values with the Roche COBAS TaqMan HIV-1 v1.0 test. At the University
      of Connecticut Health Center, a total of 349 samples from HIV-1-infected patients
      on HAART were collected and stored frozen in PPT. Viral load (VL) results were
      obtained using the Roche COBAS TaqMan HIV-1 v2.0 test (CTM v2.0) and Abbott
      RealTime HIV-1 assay (RealTime HIV-1). Of the 349 samples, 260 (74.5%) had VL
      values that differed by >0.5log10copies/mL; 64 of these were quantified by both
      assays. The remaining 196 samples were detected by CTM v2.0 but not detected in
      RealTime HIV-1: 62 of the most discordant samples in this category (CTM v2.0
      detected/RealTime HIV-1 not detected) were further analyzed using two nested RT
      PCR assays targeting pol integrase: full-length (864nt) and a highly conserved
      subregion (134nt). No HIV-1 RNA was detected in the discordant samples,
      confirming RealTime HIV-1 results. The increase in VL reactivity with the CTM
      v2.0 assay was presumably due to proviral DNA captured by the CTM total nucleic
      acid extraction chemistry but not the RNA-specific extraction procedure used in
      RealTime HIV-1. These results suggest that using CTM v2.0 with samples frozen in
      PPT could have significant clinical implications for HIV-1 patient management. 

PMID- 24747108
TI  - Nitric oxide is required for determining root architecture and lignin composition
      in sunflower. Supporting evidence from microarray analyses.
AB  - Nitric oxide (NO) is a signal molecule involved in several physiological
      processes in plants, including root development. Despite the importance of NO as
      a root growth regulator, the knowledge about the genes and metabolic pathways
      modulated by NO in this process is still limited. A constraint to unravel these
      pathways has been the use of exogenous applications of NO donors that may produce
      toxic effects. We have analyzed the role of NO in root architecture through the
      depletion of endogenous NO using the scavenger cPTIO. Sunflower seedlings growing
      in liquid medium supplemented with cPTIO showed unaltered primary root length
      while the number of lateral roots was deeply reduced; indicating that endogenous
      NO participates in determining root branching in sunflower. The transcriptional
      changes induced by NO depletion have been analyzed using a large-scale approach.
      A microarray analysis showed 330 genes regulated in the roots (p<=0.001) upon
      endogenous NO depletion. A general cPTIO-induced up-regulation of genes involved
      in the lignin biosynthetic pathway was observed. Even if no detectable changes in
      total lignin content could be detected, cell walls analyses revealed that the
      ratio G/S lignin increased in roots treated with cPTIO. This means that
      endogenous NO may control lignin composition in planta. Our results suggest that
      a fine tuning regulation of NO levels could be used by plants to regulate root
      architecture and lignin composition. The functional implications of these
      findings are discussed.

PMID- 24747109
TI  - Reprint of "Influence of analytical bias and imprecision on the number of false
      positive results using Guideline-Driven Medical Decision Limits".
AB  - BACKGROUND: Diagnostic decisions based on decision limits according to medical
      guidelines are different from the majority of clinical decisions due to the
      strict dichotomization of patients into diseased and non-diseased. Consequently,
      the influence of analytical performance is more critical than for other
      diagnostic decisions where much other information is included. The aim of this
      opinion paper is to investigate consequences of analytical quality and other
      circumstances for the outcome of "Guideline-Driven Medical Decision Limits".
      TERMS: Effects of analytical bias and imprecision should be investigated
      separately and analytical quality specifications should be estimated accordingly.
      BIOLOGICAL VARIATION AND ANALYTICAL PERFORMANCE: Use of sharp decision limits
      doesn't consider biological variation and effects of this variation are closely
      connected with the effects of analytical performance. Such relationships are
      investigated for the guidelines for HbA1c in diagnosis of diabetes and in risk of
      coronary heart disease based on serum cholesterol. The effects of a second
      sampling in diagnosis give dramatic reduction in the effects of analytical
      quality showing minimal influence of imprecision up to 3 to 5% for two
      independent samplings, whereas the reduction in bias is more moderate and a 2%
      increase in concentration doubles the percentage of false positive diagnoses,
      both for HbA1c and cholesterol. FREQUENCY OF FOLLOW-UP LABORATORY TESTS: An
      alternative approach comes from the current application of guidelines for follow
      up laboratory tests according to clinical procedure orders, e.g. frequency of
      parathyroid hormone requests as a function of serum calcium concentrations. Here,
      the specifications for bias can be evaluated from the functional increase in
      requests for increasing serum calcium concentrations. PROBABILITY FUNCTION FOR
      DIAGNOSES: In consequence of the difficulties with biological variation and the
      practical utilization of concentration dependence of frequency of follow-up
      laboratory tests already in use, a kind of probability function for diagnosis as
      function of the key-analyte is proposed.

PMID- 24747110
TI  - Calculation of LDL apoB.
AB  - OBJECTIVES: This study tests the validity of the Hattori formula to calculate LDL
      apoB based on plasma lipids and total apoB. METHODS: In 2178 patients in a
      tertiary care lipid clinic, LDL apoB calculated as suggested by Hattori et al.
      was compared to directly measured LDL apoB isolated by ultracentrifugation.
      RESULTS: In subjects with plasma triglycerides >= 3.0 mmol/L, there was
      considerable discordance between calculated and measured LDL apoB. In all others,
      the relation between measured LDL apoB and calculated LDL apoB could be expressed
      as LDL apoB = 0.86 [total apoB - 0.9 TC (mg/dL) + 0.09 HDL-C (mg/dL) - 0.08 TG
      (mg/dL)] - 7.0 (r > 0.91; P < 0.0001). CONCLUSIONS: Our results indicate that LDL
      apoB can be calculated with reasonable accuracy when triglycerides are <3.0
      mmol/L. However, the calculation suggested by Hattori et al. should be corrected
      based on the regression demonstrated between calculated and measured LDL apoB in
      subjects with a plasma triglyceride <3.0 mmol/L.

PMID- 24747111
TI  - Group 1B phospholipase A2 inactivation suppresses atherosclerosis and metabolic
      diseases in LDL receptor-deficient mice.
AB  - OBJECTIVE: Previous studies have shown that inactivation of the group 1B
      phospholipase A2 (Pla2g1b) suppresses diet-induced obesity, hyperglycemia,
      insulin resistance, and hyperlipidemia in C57BL/6 mice. A possible influence of
      Pla2g1b inactivation on atherosclerosis has not been addressed previously. The
      current study utilized LDL receptor-deficient (Ldlr(-/-)) mice with plasma lipid
      levels and distribution similar to hyperlipidemic human subjects as a preclinical
      animal model to test the effectiveness of Pla2g1b inactivation on
      atherosclerosis. METHODS AND RESULTS: The Pla2g1b(+/+)Ldlr(-/-) and Pla2g1b(-/
      )Ldlr(-/-) mice were fed a low fat chow diet or a hypercaloric diet with 58.5
      kcal% fat and 25 kcal% sucrose for 10 weeks. Minimal differences were observed
      between Pla2g1b(+/+)Ldlr(-/-) and Pla2g1b(-/-)Ldlr(-/-) mice when the animals
      were maintained on the low fat chow diet. However, when the animals were
      maintained on the hypercaloric diet, the Pla2g1(+/+)Ldlr(-/-) mice showed the
      expected body weight gain but the Pla2g1b(-/-)Ldlr(-/-) mice were resistant to
      diet-induced body weight gain. The Pla2g1b(-/-)Ldlr(-/-) mice also displayed
      lower fasting glucose, insulin, and plasma lipid levels compared to the
      Pla2g1b(+/+)Ldlr(-/-) mice, which displayed robust hyperglycemia,
      hyperinsulinemia, and hyperlipidemia in response to the hypercaloric diet.
      Importantly, atherosclerotic lesions in the aortic roots were also reduced 7-fold
      in the Pla2g1b(-/-)Ldlr(-/-) mice. CONCLUSION: The effectiveness of Pla2g1b
      inactivation to suppress diet-induced body weight gain and reduce diabetes and
      atherosclerosis in LDL receptor-deficient mice suggests that pharmacological
      inhibition of Pla2g1b may be a viable strategy to decrease diet-induced obesity
      and the risk of diabetes and atherosclerosis in humans.

PMID- 24747112
TI  - Statins and periodontal inflammation: a pleiotropic effect of statins or a
      pleiotropic effect of LDL-cholesterol lowering?

PMID- 24747113
TI  - Cigarette smoke condensate affects monocyte interaction with endothelium.
AB  - OBJECTIVE: Circulating monocytes adhere to the endothelium and migrate into the
      intima contributing to atherosclerotic plaque growth. Cigarette smoke is a risk
      factor for atherosclerosis, but it is not completely known how it affects
      monocyte behavior in atherogenesis. METHODS: We studied the effects of cigarette
      smoke condensate (CSC) on human monocytes (HM) chemotaxis and transmigration
      through an endothelial cell (EC) monolayer. RESULTS: Pre-treatment with CSC
      caused a decrease in HM chemotaxis and transmigration (-55% and -18% vs control,
      p < 0.05, respectively), paralleled by a reduced expression of Rac 1 GTPase. On
      the contrary, direct exposure of both HM and EC to CSC increased (+23% vs
      control, p < 0.05) HM transmigration, paralleled by a strong stimulation of VCAM1
      and ICAM1 expression by ECs, and by a slight increase in monocyte integrin
      expression. An enhancement of monocyte transmigration was obtained after the
      exposure of both HM and EC to medium conditioned by HM previously incubated with
      CSC (+265% vs control, p < 0.001). CSC showed a stimulatory effect on the
      expression by HM of TLR4, MCP1, IL8, IL1beta, and TNFalfa, which was ablated by
      pre treatment with PDTC. Incubation with neutralizing antibodies against both
      MCP1 or IL8 completely abolished the CSC-conditioned medium induced HM
      transmigration. CONCLUSIONS: CSC induces HM to release chemotactic factor(s),
      which amplify the recruitment and transmigration of inflammatory cells through
      EC, but CSC may also reduce HM migratory capacity. Therefore, exposure to CSC
      affects monocyte behavior and interaction with the endothelium, thus potentially
      facilitating and/or further aggravating the atherogenic process.

PMID- 24747114
TI  - Downregulation of the glucocorticoid-induced leucine zipper (GILZ) promotes
      vascular inflammation.
AB  - OBJECTIVE: Glucocorticoid-induced leucine zipper (GILZ) represents an anti
      inflammatory mediator, whose downregulation has been described in various
      inflammatory processes. Aim of our study was to decipher the regulation of GILZ
      in vascular inflammation. APPROACH AND RESULTS: Degenerated aortocoronary
      saphenous vein bypass grafts (n = 15), which exhibited inflammatory cell
      activation as determined by enhanced monocyte chemoattractrant protein 1 (MCP-1,
      CCL2) and Toll-like receptor 2 (TLR2) expression, showed significantly diminished
      GILZ protein and mRNA levels compared to healthy veins (n = 23). GILZ was also
      downregulated in human umbilical vein endothelial cells (HUVEC) and macrophages
      upon treatment with the inflammatory cytokine TNF-alpha in a tristetraprolin
      (ZFP36, TTP)- and p38 MAPK-dependent manner. To assess the functional
      implications of decreased GILZ expression, we determined NF-kappaB activation
      after GILZ knockdown by siRNA and found that NF-kappaB activity and inflammatory
      gene expression were significantly enhanced. Importantly, ZFP36 is induced in TNF
      alpha-activated HUVEC as well as in degenerated vein bypasses. When
      atheroprotective laminar shear stress was employed, GILZ levels in HUVEC
      increased on mRNA and protein level. Laminar flow also counteracted TNF-alpha
      induced ZFP36 expression and GILZ downregulation. MAP kinase phosphatase 1 (MKP
      1, DUSP1), a negative regulator of ZFP36 expression, was distinctly upregulated
      under laminar shear stress conditions and downregulated in degenerated vein
      bypasses. CONCLUSION: Our data show a diminished expression of the anti
      inflammatory mediator GILZ in the inflamed vasculature and indicate that GILZ
      downregulation requires the mRNA binding protein ZFP36. We suggest that reduced
      GILZ levels play a role in cardiovascular disease.

PMID- 24747116
TI  - Mechanistic studies on formation of the dinitrosyl iron complex of the [2Fe-2S]
      cluster of SoxR protein.
AB  - The transcriptional activation of SoxR in Escherichia coli occurs through direct
      modification of the [2Fe-2S] by nitric oxide (NO) to form a dinitrosyl iron
      complex (DNIC). Here, we investigated the reactions of NO with [2Fe-2S] clusters
      of SoxR; the results were compared with those obtained for spinach ferredoxin
      (Fd). UV-visible absorption and ESR spectra of SoxR upon treatment with an NO
      donor showed the formation of DNIC of SoxR efficiently, whereas those of Fd
      exhibited small changes. Upon pulse radiolysis of a deaerated solution of SoxR in
      the presence of sodium nitrite, a biphasic change in absorption, consisting of a
      faster phase and a slower phase, was observed. The slower phase fraction was
      increased with increases in the [NO]/[SoxR] molar ratio, reaching a plateau at ~2
      equivalents of NO. On the basis of these results, we propose that the faster
      phase corresponds to the reaction of the first NO molecule with [2Fe-2S] of SoxR,
      followed by the reaction of the second NO molecule. In the reaction of NO with
      Fd, no slower phase was observed. These results suggest that the reaction of the
      second equivalent of NO is an important process for the formation of DNIC. 

PMID- 24747115
TI  - Incremental replacement of saturated fats by n-3 fatty acids in high-fat, high
      cholesterol diets reduces elevated plasma lipid levels and arterial lipoprotein
      lipase, macrophages and atherosclerosis in LDLR-/- mice.
AB  - OBJECTIVE: Effects of progressive substitution of dietary n-3 fatty acids (FA)
      for saturated FA (SAT) on modulating risk factors for atherosclerosis have not
      been fully defined. Our previous reports demonstrate that SAT increased, but n-3
      FA decreased, arterial lipoprotein lipase (LpL) levels and arterial LDL
      cholesterol deposition early in atherogenesis. We now questioned whether
      incremental increases in dietary n-3 FA can counteract SAT-induced pro
      atherogenic effects in atherosclerosis-prone LDL-receptor knockout (LDLR-/-) mice
      and have identified contributing mechanisms. METHODS AND RESULTS: Mice were fed
      chow or high-fat diets enriched in SAT, n-3, or a combination of both SAT and n-3
      in ratios of 3:1 (S:n-3 3:1) or 1:1 (S:n-3 1:1). Each diet resulted in the
      expected changes in fatty acid composition in blood and aorta for each feeding
      group. SAT-fed mice became hyperlipidemic. By contrast, n-3 inclusion decreased
      plasma lipid levels, especially cholesterol. Arterial LpL and macrophage levels
      were increased over 2-fold in SAT-fed mice but these were decreased with
      incremental replacement with n-3 FA. n-3 FA partial inclusion markedly decreased
      expression of pro-inflammatory markers (CD68, IL-6, and VCAM-1) in aorta. SAT
      diets accelerated advanced atherosclerotic lesion development, whereas all n-3 FA
      containing diets markedly slowed atherosclerotic progression. CONCLUSION:
      Mechanisms whereby dietary n-3 FA may improve adverse cardiovascular effects of
      high-SAT, high-fat diets include improving plasma lipid profiles, increasing
      amounts of n-3 FA in plasma and the arterial wall. Even low levels of replacement
      of SAT by n-3 FA effectively reduce arterial lipid deposition by decreasing
      aortic LpL, macrophages and pro-inflammatory markers.

PMID- 24747118
TI  - Evolutionary Tradeoffs.

PMID- 24747117
TI  - The nature of replication of tick-borne encephalitis virus strains isolated from
      residents of the Russian Far East with inapparent and clinical forms of
      infection.
AB  - We describe the biological properties and molecular characteristics of complete
      genomes of 33 tick-borne encephalitis virus (TBEV) strains that induced different
      forms of infection, from inapparent to severe focal ones resulting in fatal
      outcome. Hemagglutinating activity of Oshima-like strains was higher at pH 5.8,
      while activity of Sofjin- and Senhzang-like strains were higher at pH 6.2 and
      6.8, respectively. We determined susceptibility of porcine kidney (PK) cell
      cultures to these TBEV strains by cytopathic effect (CPE), plaque formation, and
      size of plaques. The clinical TBEV strains had higher virus titers both in tissue
      culture infectious dose 50(TCID50) and in plaque-forming unit (PFU) titers and
      larger plaques than the inapparent strains. A comparison of virus multiplication
      kinetics by PFU in culture fluid with kinetics of ELISA antigen and hemagglutinin
      accumulation suggested a different mechanism of interaction between these virus
      strains and PK cells at the initial stage of cell infection. 

PMID- 24747119
TI  - Inflammatory Bowel Disease.

PMID- 24747120
TI  - Investigating the effectiveness of pictorial health warnings in Mauritius:
      findings from the ITC Mauritius survey.
AB  - INTRODUCTION: Health warnings on tobacco packages are an effective strategy for
      informing the public about the harms associated with tobacco use. Most studies
      investigating the effectiveness of pictorial health warnings (PHWs) on cigarette
      packages are from high-income countries. This study evaluated the impact of PHWs
      on smokers' perceptions and behavior in Mauritius, the first country in the World
      Health Organization African region to implement PHWs. METHODS: Data were drawn
      from 3 waves of a nationally representative cohort of adult smokers from the
      International Tobacco Control (ITC) Mauritius Survey (n = 668). Wave 1 was
      conducted in 2009, 6 months prior to the implementation of PHWs. Waves 2 and 3
      were conducted 10-12 months and 20-21 months, respectively, postimplementation.
      Six established indicators of warning effectiveness were used to evaluate the
      effect of PHWs on smokers' perceptions and behavior. RESULTS: All indicators of
      warning effectiveness (salience, cognitive, and behavioral reactions) and the
      Label Impact Index, a weighted combination of 4 indicators, increased
      significantly between Waves 1 and 2. However, between Waves 2 and 3, there was a
      significant decline in the proportion of smokers who reported "avoiding looking"
      at labels. CONCLUSIONS: This study found that implementation of PHWs in Mauritius
      significantly enhanced the effectiveness of warnings, illustrating their value
      for other countries, particularly in Africa, at an early stage in tobacco
      control. The study also demonstrates the importance of revising PHWs to
      counteract wearout. The introduction of PHWs in Mauritius clearly demonstrates
      the benefits of employing an evidence-based approach to strengthen tobacco
      control policies.

PMID- 24747121
TI  - Sulforaphane inhibits phorbol ester-stimulated IKK-NF-kappaB signaling and COX-2
      expression in human mammary epithelial cells by targeting NF-kappaB activating
      kinase and ERK.
AB  - Sulforaphane, an isothiocyanate present in cruciferous vegetables, has been
      reported to possess anti-inflammatory and cancer chemopreventive properties.
      However, the molecular mechanisms by which sulforaphane suppresses inflammation
      and carcinogenesis are yet to be fully elucidated. Since the aberrant expression
      of cyclooxygenase-2 (COX-2) links inflammation and cancer, the present study was
      aimed to elucidate the mechanisms by which sulforaphane modulates COX-2
      overexpression in human mammary epithelial (MCF-10A) cells stimulated with a
      prototypic tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA). Treatment
      of MCF-10A cells with sulforaphane significantly inhibited TPA-induced expression
      of COX-2 protein and its mRNA transcript. Transient transfection of cells with
      deletion mutant constructs of COX-2 promoter revealed that the transcription
      factor nuclear factor-kappaB (NF-kappaB) plays a key role in TPA-induced COX-2
      expression in MCF-10A cells. Pretreatment with sulforaphane significantly
      attenuated nuclear localization, DNA binding and the transcriptional activity of
      NF-kappaB through inhibition of phosphorylation and subsequent degradation of
      IkappaBalpha in MCF-10A cells stimulated with TPA. Sulforaphane also attenuated
      TPA-induced activation of IkappaB kinases (IKK), NF-kappaB-activating kinase
      (NAK) and extracellular signal-regulated kinase-1/2 (ERK1/2). Pharmacological
      inhibition of IKK or transient transfection of cells with dominant-negative
      mutant forms of this kinase abrogated TPA-induced NF-kappaB activation and COX-2
      expression. In addition, the blockade of ERK1/2 activation negated the catalytic
      activity of IKKalpha, but not that of IKKbeta, whereas silencing NAK by specific
      siRNA abrogated the IKKbeta activity in TPA-treated cells. Taken together,
      sulforaphane inhibits TPA-induced NF-kappaB activation and COX-2 expression in
      MCF-10A cells by blocking two distinct signaling pathways mediated by ERK1/2
      IKKalpha and NAK-IKKbeta.

PMID- 24747122
TI  - AST1306, a potent EGFR inhibitor, antagonizes ATP-binding cassette subfamily G
      member 2-mediated multidrug resistance.
AB  - AST1306, an inhibitor of EGFR and ErbB2, is currently in phase I of clinical
      trials. We evaluated the effect of AST306 on the reversal of multidrug resistance
      (MDR) induced by ATP-binding cassette (ABC) transporters. We found that AST1306
      significantly sensitized the ABC subfamily G member 2 (ABCG2)-overexpressing
      cells to ABCG2 substrate chemotherapeutics. AST1306 significantly increased
      intracellular accumulation of [(3)H]-mitoxantrone in ABCG2-overexpressing cells
      by blocking ABCG2 efflux function. Moreover, AST1306 stimulated the ATPase
      activity of ABCG2. Homology modeling predicted the binding conformation of
      AST1306 to be within the transmembrane region of ABCG2. In conclusion, AST1306
      could notably reverse ABCG2-mediated MDR. 

PMID- 24747123
TI  - Fulvestrant treatment alters MDM2 protein turnover and sensitivity of human
      breast carcinoma cells to chemotherapeutic drugs.
AB  - The human homologue of mouse double minute 2 (MDM2) is overexpressed in tumors
      and contributes to tumorigenesis through inhibition of p53 activity. We
      investigated the effect of the anti-estrogen fulvestrant on MDM2 expression and
      sensitivity of estrogen receptor positive human breast cancer cell lines to
      chemotherapeutics. Fulvestrant down-regulated MDM2 through increased protein
      turnover. Fulvestrant blocked estrogen-dependent up-regulation of MDM2 and
      decreased basal expression of MDM2 in the absence of estradiol. As combinations
      of fulvestrant with doxorubicin, etoposide or paclitaxel were synergistic,
      altering cell cycle distribution and increasing cell death, this provides
      rationale for testing combinatorial chemotherapy with fulvestrant as a novel
      therapeutic strategy for patients with advanced breast cancer. 

PMID- 24747124
TI  - Jellyfish venomics and venom gland transcriptomics analysis of Stomolophus
      meleagris to reveal the toxins associated with sting.
AB  - Jellyfish Stomolophus meleagris is a very dangerous animal because of its strong
      toxicity. However, the composition of the venom is still unclear. Both proteomics
      and transcriptomics approaches were applied in present study to investigate the
      major components and their possible relationships to the sting. The proteomics of
      the venom from S. meleagris was conducted by tryptic digestion of the crude venom
      followed by RP-HPLC separation and MS/MS analysis of the tryptic peptides. The
      venom gland transcriptome was analyzed using a high-throughput Illumina
      sequencing platform HiSeq 2000 with de novo assembly. A total of 218 toxins were
      identified including C-type lectin, phospholipase A2 (PLA2), potassium channel
      inhibitor, protease inhibitor, metalloprotease, hemolysin and other toxins, most
      of which should be responsible for the sting. Among them, serine protease
      inhibitor, PLA2, potassium channel inhibitor and metalloprotease are predominant,
      representing 28.44%, 21.56%, 16.06% and 15.14% of the identified venom proteins,
      respectively. Overall, our combined proteomics and transcriptomics approach
      provides a systematic overview of the toxins in the venom of jellyfish S.
      meleagris and it will be significant to understand the mechanism of the sting.
      BIOLOGICAL SIGNIFICANCE: Jellyfish Stomolophus meleagris is a very dangerous
      animal because of its strong toxicity. It often bloomed in the coast of China in
      recent years and caused thousands of people stung and even deaths every year.
      However, the components which caused sting are still unknown yet. In addition, no
      study about the venomics of jellyfish S. meleagris has been reported. In the
      present study, both proteomics and transcriptomics approaches were applied to
      investigate the major components related to the sting. The result showed that
      major component included C-type lectin, phospholipase A2, potassium channel
      inhibitor, protease inhibitor, metalloprotease, hemolysin and other toxins, which
      should be responsible for the effect of sting. This is the first research about
      the venomics of jellyfish S. meleagris. It will be significant to understand the
      mechanism of the biological effects and helpful to develop ways to deal with the
      sting.

PMID- 24747125
TI  - The human HDL proteome displays high inter-individual variability and is altered
      dynamically in response to angioplasty-induced atheroma plaque rupture.
AB  - Recent findings support potential roles for HDL in cardiovascular pathophysiology
      not related to lipid metabolism. We address whether HDL proteome is dynamically
      altered in atheroma plaque rupture. We used immunoaffinity purification of HDL
      samples from coronary artery disease patients before and after percutaneous
      transluminal coronary angioplasty (PTCA), a model of atheroma plaque disruption.
      Samples were analyzed by quantitative proteomics using stable isotope labeling
      and results were subjected to statistical analysis of protein variance using a
      novel algorithm. We observed high protein variability in HDL composition between
      individuals, indicating that HDL protein composition is highly patient-specific.
      However, intra-individual protein variances remained at low levels, confirming
      the reproducibility of the method used for HDL isolation and protein
      quantification. A systems biology analysis of HDL protein alterations induced by
      PTCA revealed an increase in two protein clusters that included several
      apolipoproteins, fibrinogen-like protein 1 and other intracellular proteins, and
      a decrease in antithrombin-III, annexin A1 and several immunoglobulins. Our
      results support the concept of HDL as dynamic platforms that donate and receive a
      variety of molecules and provide an improved methodology to use HDL proteome for
      the systematic analysis of differences among individuals and the search for
      cardiovascular biomarkers. Biological significance The HDL proteome is an
      interesting model of clinical relevance and has been previously described to be
      dynamically altered in response to pathophysiological conditions and
      cardiovascular diseases. Our study suggests that interindividual variability of
      HDL proteome is higher than previously thought and provided the detection of a
      set of proteins that changed their abundance in response to plaque rupture,
      supporting the concept of HDL as dynamic platforms that donate and receive a
      variety of molecules. 

PMID- 24747126
TI  - Biogeographic history of Pistacia (Anacardiaceae), emphasizing the evolution of
      the Madrean-Tethyan and the eastern Asian-Tethyan disjunctions.
AB  - Pistacia L. exhibits a disjunct distribution in Mediterranean Eurasia and
      adjacent North Africa, eastern Asia, and North to Central America. The spatio
      temporal diversification history of Pistacia was assessed to test hypotheses on
      the Madrean-Tethyan and the Eurasian Tethyan disjunctions through phylogenetic
      and biogeographic analyses. Maximum parsimony and Bayesian methods were employed
      to analyze sequences of multiple nuclear and plastid loci of Pistacia species.
      Bayesian dating analysis was conducted to estimate the divergence times of
      clades. The likelihood method LAGRANGE was used to infer ancestral areas. The New
      World species of Pistacia formed a clade sister to the Old World clade in all
      phylogenetic analyses. The eastern Asian Pistacia weinmannifolia-P.
      cucphuongensis clade was sister to a clade of the remaining Old World species,
      which were further resolved into three subclades. Pistacia was estimated to have
      originated at 37.60 mya (with 95% highest posterior density interval (HPD): 25.42
      48.51 mya). A vicariance event in the early Miocene (19.79 mya with 95% HPD:
      10.88-30.36 mya) was inferred to account for the intercontinental disjunction
      between the New World and the Old World species, which is consistent with the
      Madrean-Tethyan hypothesis. The two Old World eastern Asian-Tethyan disjunctions
      are best explained by one vicariance event in the early Miocene (15.87 mya with
      95% HPD: 8.36-24.36 mya) and one dispersal event in late Miocene (5.89 mya with
      95% HPD: 2.68-9.16 mya). The diversification of the Old World Pistacia species
      was significantly affected by extensive geological and climatic changes in the
      Qinghai-Tibetan plateau (QTP) and in the Mediterranean region.

PMID- 24747127
TI  - Mosaic origins of Bradyrhizobium legume symbionts on the Caribbean island of
      Guadeloupe.
AB  - To analyze geographic affinities of Bradyrhizobium sp. symbionts associated with
      the diverse legume flora on the Caribbean island of Guadeloupe, 39 isolates from
      18 legume genera were compared to a reference set of 269 Bradyrhizobium strains
      from North America, Central America, Puerto Rico and the Philippines. A
      multilocus sequence analysis (4192 bp) showed that nucleotide diversity in
      Guadeloupe equaled or exceeded that found in all other regional Bradyrhizobium
      populations examined. Bayesian phylogenetic tree analysis grouped the Guadeloupe
      Bradyrhizobium strains into clades with at least 20 distinct sets of non
      Guadeloupe relatives, implying that the island was colonized numerous times from
      multiple source regions. However, for 18% of the Guadeloupe isolates, inferred
      geographic affinities for the nifD locus, in the symbiosis island region of the
      Bradyrhizobium chromosome, conflicted with the source region deduced from a tree
      based on six concatenated housekeeping genes. Geographic mosaic ancestry was
      therefore evident among Guadeloupe bradyrhizobia. Horizontal gene transfer
      subsequent to island colonization appears to have generated strains that carry
      combinations of genes from disparate source regions.

PMID- 24747128
TI  - A new phylogenetic analysis sheds new light on the relationships in the Calanthe
      alliance (Orchidaceae) in China.
AB  - The taxonomy of the Calanthe alliance (Epidendroideae, Orchidaceae), consisting
      of Calanthe, Cephalantheropsis, and Phaius, has been difficult for orchidologists
      to understand because of the presence of common morphological features. In this
      study, in addition to morphological and geographical analyses, maximum parsimony
      and Bayesian inference analyses were performed based on nucleotide sequences of
      the nuclear internal transcribed spacer and cpDNA genes of 88 taxa representing
      the major clades of the Calanthe alliance in China. The results indicated that
      Cephalantheropsis is monophyletic, while both Phaius and Calanthe are
      polyphyletic. In Phaius, a total of three species, P. flavus, P. columnaris, and
      P. takeoi, were segregated to form a new genus, Paraphaius. In Calanthe, subgenus
      Preptanthe and sect. Styloglossum were both categorized as distinct genera from
      Calanthe. Our results also confirm that Calanthe delavayi and C. calanthoides are
      members of Calanthe. Previous studies assigned C. delavayi to Phaius and C.
      calanthoides to Ghiesbrechtia. Five sections, namely, Alpinocalanthe, Puberula,
      Ghiesbrechtia, Tricarinata, and Calanthe, three of which are new taxa, were
      recognized in Calanthe. Therefore, we propose that the Calanthe alliance is
      composed of six genera: Calanthe, Cephalantheropsis, Paraphaius, Phaius,
      Preptanthe and Styloglossum.

PMID- 24747129
TI  - Using multiple relaxed-clock models to estimate evolutionary timescales from DNA
      sequence data.
AB  - Molecular data sets comprising DNA sequences from multiple genes are now
      commonplace in phylogenetic studies. These data sets should be analysed using
      methods that can account for heterogeneity in the molecular evolutionary process
      among genes. A common problem is determining how many evolutionary models should
      be applied to subsets of the data. Different genes can exhibit differing patterns
      of rate variation among lineages, making it appropriate to assign a separate
      molecular-clock model to each subset of the data (i.e., a 'partitioned' clock
      model). The impact of clock-partitioning on estimates of evolutionary rates and
      timescales is largely unknown. In this study, we use a recently developed method,
      ClockstaR, to evaluate the effect of using different clock-partitioning schemes.
      We conduct Bayesian phylogenetic analyses of simulated and empirical multigene
      data sets. Our analyses show strong statistical support for the clock
      partitioning scheme chosen by ClockstaR. In addition, we find that the optimal
      clock-partitioning scheme produces more reliable estimates of node ages than
      other schemes. 

PMID- 24747131
TI  - NBT-II cell locomotion is modulated by restricting the size of focal contacts and
      is improved through EGF and ROCK signaling.
AB  - Focal contacts, large macromolecular complexes that link the extracellular matrix
      and the internal cell cytoskeleton, are thought to govern cell locomotion.
      However, the maturation process through which focal contacts control the cellular
      migratory machinery by changes in size and molecular composition remain unclear.
      Here, we fabricated cell growth substrates that contained linear ECM strips of
      micron- or submicron-width in order to limit the enlargement of focal contacts.
      We found that NBT-II cells plated on the submicron substrate possessed smaller
      focal complexes that exhibited a highly dynamic turnover. These cells possessed
      various leading edges at multiple sites of the cell periphery, which prevented
      the cell from advancing. In contrast, cells grown on the micron-width substrate
      possessed large and stable focal adhesions. Most of these cells were elongated
      bipolar cells that were tethered at both ends and were immobile. Further, EGF and
      ROCK signaling pathways can modulate the cellular migratory responses according
      to the substrate guidance. On the submicron-width substrate, EGF treatment
      increased the focal contact size and the contractile force, causing these cells
      to develop one leading edge and migrate along the submicron-sized ECM paths. In
      contrast, inhibition of ROCK signaling decreased the focal contact size for cells
      plated on the micron substrate. These cells became less tethered and were able to
      migrate along or even across the micron-sized ECM paths. Our results indicate
      that formation and maturation of focal contacts is controlled by both ECM cues
      and intracellular signaling and they play a central role in directed cell motion.

PMID- 24747130
TI  - A multigene phylogenetic synthesis for the class Lecanoromycetes (Ascomycota):
      1307 fungi representing 1139 infrageneric taxa, 317 genera and 66 families.
AB  - The Lecanoromycetes is the largest class of lichenized Fungi, and one of the most
      species-rich classes in the kingdom. Here we provide a multigene phylogenetic
      synthesis (using three ribosomal RNA-coding and two protein-coding genes) of the
      Lecanoromycetes based on 642 newly generated and 3329 publicly available
      sequences representing 1139 taxa, 317 genera, 66 families, 17 orders and five
      subclasses (four currently recognized: Acarosporomycetidae, Lecanoromycetidae,
      Ostropomycetidae, Umbilicariomycetidae; and one provisionarily recognized,
      'Candelariomycetidae'). Maximum likelihood phylogenetic analyses on four
      multigene datasets assembled using a cumulative supermatrix approach with a
      progressively higher number of species and missing data (5-gene, 5+4-gene, 5+4+3
      gene and 5+4+3+2-gene datasets) show that the current classification includes non
      monophyletic taxa at various ranks, which need to be recircumscribed and require
      revisionary treatments based on denser taxon sampling and more loci. Two newly
      circumscribed orders (Arctomiales and Hymeneliales in the Ostropomycetidae) and
      three families (Ramboldiaceae and Psilolechiaceae in the Lecanorales, and
      Strangosporaceae in the Lecanoromycetes inc. sed.) are introduced. The potential
      resurrection of the families Eigleraceae and Lopadiaceae is considered here to
      alleviate phylogenetic and classification disparities. An overview of the
      photobionts associated with the main fungal lineages in the Lecanoromycetes based
      on available published records is provided. A revised schematic classification at
      the family level in the phylogenetic context of widely accepted and newly
      revealed relationships across Lecanoromycetes is included. The cumulative
      addition of taxa with an increasing amount of missing data (i.e., a cumulative
      supermatrix approach, starting with taxa for which sequences were available for
      all five targeted genes and ending with the addition of taxa for which only two
      genes have been sequenced) revealed relatively stable relationships for many
      families and orders. However, the increasing number of taxa without the addition
      of more loci also resulted in an expected substantial loss of phylogenetic
      resolving power and support (especially for deep phylogenetic relationships),
      potentially including the misplacements of several taxa. Future phylogenetic
      analyses should include additional single copy protein-coding markers in order to
      improve the tree of the Lecanoromycetes. As part of this study, a new module
      ("Hypha") of the freely available Mesquite software was developed to compare and
      display the internodal support values derived from this cumulative supermatrix
      approach. 

PMID- 24747132
TI  - Involvement of the AMPK-PTEN pathway in insulin resistance induced by high
      glucose in cultured rat podocytes.
AB  - As part of the filtration barrier, podocytes play an important role in the
      development of diabetic nephropathy. Disturbances in insulin signaling
      accompanied by insulin resistance can lead to various intracellular events. We
      hypothesized that high glucose concentrations would lead to disturbances in
      interactions between AMPK and PTEN proteins in podocytes. Experiments were
      performed in primary rat podocytes cultured with normal (5.6mM) or high (30mM)
      glucose concentrations for 5d. Immunodetection methods were used to detect AMPK,
      PTEN, insulin receptor, and Akt proteins, and their phosphorylated forms. Insulin
      stimulated changes in glucose uptake were used to detect insulin resistance.
      Isoforms of AMPK were detected by RT-PCR. AMPK and PTEN activities were modified
      by metformin, Compound C, siRNA for AMPK isoforms alpha1 and alpha2 and siRNA for
      PTEN, respectively. We found that impairment of insulin induction of glucose
      uptake into podocytes cultivated in the presence of high glucose concentrations
      for long periods of time is associated with increased PTEN levels in an AMPK
      dependent manner. 

PMID- 24747133
TI  - Association of endothelin-1 gene polymorphisms with the clinical phenotype in
      primary nephrotic syndrome of children.
AB  - AIMS: This study aims to investigate the relationship between plasma endothelin-1
      (ET-1) concentrations, ET-1 gene polymorphisms in loci rs5370, rs1630736, 3A/4A
      and clinical features of primary nephrotic syndrome (NS) in children. MATERIALS
      AND METHODS: Thirty-six children with primary NS were selected as case group, and
      94 healthy children were selected as control group. All subjects were genotyped
      for three single nucleotide polymorphisms (SNPs) (rs5370, rs10478694 [3A4A] and
      rs 1630736) in the ET-1 gene by gene sequencing. The plasma ET-1 concentrations
      were measured using a radio-immunoassay. KEY FINDINGS: Plasma ET-1 concentrations
      were higher in NS patients (P=0.007) as compared to healthy children. The allele
      frequencies between control and NS patients were significantly different only
      with respect to the rs10478694 SNP of the ET-1 gene. The allele frequencies
      between control and NS patients for the rs5370 SNP showed a trend towards
      difference (P=0.057). Plasma cholesterol in NS patients is associated with both:
      the GT genotype in locus rs5370 and the 3A4A genotype in locus rs10478694 (P<0.05
      in both cases). SIGNIFICANCE: The ET systems might play a disease modifying role
      in pediatric NS. Plasma cholesterol, a hallmark of NS, seems to be associated
      with genetic variations within the human ET-1 gene.

PMID- 24747134
TI  - Chk1 is required for the metaphase-anaphase transition via regulating the
      expression and localization of Cdc20 and Mad2.
AB  - AIMS: The checkpoint kinase 1 (Chk1) functions not only in genotoxic stresses but
      also in normal cell cycle progression, particularly in the initiation,
      progression and fidelity of unperturbed mitosis. In this study, we investigated
      the role of Chk1 in regulating the metaphase-anaphase transition in mammalian
      cells. MAIN METHODS: The mitotic progression was monitored by flow cytometry
      analysis. The levels of cyclin B1, Cdc20 and Mad2 were measured by Western
      blotting. Metaphase chromosome alignment and the subcellular localization of
      Cdc20 and Mad2 were analyzed by immunofluorescence and confocal microscopy. KEY
      FINDINGS: Cyclin B1 degradation and the metaphase-anaphase transition were
      severely blocked by Chk1 siRNA. Depletion of Chk1 induced chromosome alignment
      defect in metaphase cells. The kinetochore localization of Cdc20, Mad2 was
      disrupted in Chk1 depleted cells. Chk1 abrogation also dramatically reduced the
      protein expression levels of Cdc20 and Mad2. SIGNIFICANCE: These results strongly
      suggest that Chk1 is required for the metaphase-anaphase transition via
      regulating the subcellular localization and the expression of Cdc20 and Mad2.

PMID- 24747135
TI  - Sedum sarmentosum Bunge extract exerts renal anti-fibrotic effects in vivo and in
      vitro.
AB  - AIMS: Sedum sarmentosum Bunge, a traditional Chinese herbal medicine, has a wide
      range of clinical effects, including anti-oxidation, anti-inflammation, and anti
      cancer properties. In this study, we determined whether S. sarmentosum Bunge
      Extract (SSBE) has anti-fibrotic effects on renal tissues. MAIN METHODS: We
      investigated the effects of SSBE on aristolochic acid (AA)-induced injury to
      renal tubular epithelial cells (RTECs) in vitro and unilateral ureteral
      obstruction (UUO)-induced renal fibrosis in vivo by evaluating epithelial-to
      mesenchymal transition (EMT) and the accumulation of extracellular matrix (ECM)
      components. Furthermore, we examined the expression levels of TGF-beta1 and its
      receptor. KEY FINDINGS: In cultured RTECs (NRK-52E), AA promoted renal EMT and
      ECM accumulation by up-regulating the expression of mesenchymal markers and ECM
      components and by down-regulating the expression of epithelial markers. In
      addition, AA induced an imbalance between MMP-2 and TIMP-2 and enhanced
      expression of TGF-beta1 and its receptor. SSBE treatment significantly inhibited
      AA-induced TGF-beta1 expression and prevented the induction of EMT and deposition
      of ECM. In the UUO rats, tubular injury and interstitial fibrosis were obviously
      increased. SSBE administration protected renal function, as indicated by reduced
      serum creatinine levels, and alleviated renal interstitial fibrosis. These anti
      fibrotic effects were associated with a reduction in TGF-beta1 expression and
      inhibition of EMT and ECM accumulation. SIGNIFICANCE: These findings suggest that
      SSBE may have therapeutic potential for fibrotic kidney diseases.

PMID- 24747136
TI  - End o' the line revisited: moving on from nitric oxide to CGRP.
AB  - When endothelin-1(ET-1) was discovered it was hailed as the prototypical
      endothelium-derived contracting factor (EDCF). However, over the years little
      evidence emerged convincingly demonstrating that the peptide actually contributes
      to moment-to-moment changes in vascular tone elicited by endothelial cells. This
      has been attributed to the profound inhibitory effect of nitric oxide (NO) on
      both the production (by the endothelium) and the action (on vascular smooth
      muscle) of ET-1. Hence, the peptide is likely to initiate acute changes in
      vascular diameter only under extreme conditions of endothelial dysfunction when
      the NO bioavailability is considerably reduced if not absent. The present essay
      discusses whether or not this concept should be revised, in particular in view of
      the potent inhibitory effect exerted by calcitonin gene related peptide (CGRP)
      released from sensorimotor nerves on vasoconstrictor responses to ET-1. 

PMID- 24747137
TI  - The detrimental effects of acute hyperglycemia on myocardial glucose uptake.
AB  - AIMS: Although acute hyperglycemic (AHG) episodes are linked to lower glucose
      uptake, underlying mechanisms remain unclear. We hypothesized that AHG triggers
      reactive oxygen species (ROS) production and increases non-oxidative glucose
      pathway (NOGP) activation, i.e. stimulation of advanced glycation end products
      (AGE), polyol pathway (PP), hexosamine biosynthetic pathway (HBP), PKC; thereby
      decreasing cardiac glucose uptake. MAIN METHODS: H9c2 cardiomyoblasts were
      exposed to 25 mM glucose for 24h vs. 5.5mM controls +/- modulating agents during
      the last hour of glucose exposure: a) antioxidant #1 for mitochondrial ROS (250
      MUM 4-OHCA), b) antioxidant #2 for NADPH oxidase-generated ROS (100 MUM DPI), c)
      NOGP inhibitors - 100 MUM aminoguanidine (AGE), 5 MUM chelerythrine (PKC); 40 MUM
      DON (HBP); and 10 MUM zopolrestat (PP). ROS levels (mitochondrial, intracellular)
      and glucose uptake were evaluated by flow cytometry. KEY FINDINGS: AHG elevated
      ROS, activated NOGPs and blunted glucose uptake. Transketolase activity (pentose
      phosphate pathway [PPP] marker) did not change. Respective 4-OHCA and DPI
      treatment blunted ROS production, diminished NOGP activation and normalized
      glucose uptake. NOGP inhibitory studies identified PKCbetaII as a key downstream
      player in lowering insulin-mediated glucose uptake. When we employed an agent
      (benfotiamine) known to shunt flux away from NOGPs (into PPP), it decreased ROS
      generation and NOGP activation, and restored glucose uptake under AHG conditions.
      SIGNIFICANCE: This study demonstrates that AHG elicits maladaptive events that
      function in tandem to reduce glucose uptake, and that antioxidant treatment
      and/or attenuation of NOGP activation (PKC, polyol pathway) may limit the onset
      of insulin resistance.

PMID- 24747138
TI  - Biotransformation of phytosterols under aerobic conditions.
AB  - Phytosterols are plant-derived sterols present in pulp and paper wastewater and
      have been implicated in the endocrine disruption of aquatic species. Bioassays
      were performed to assess the effect of an additional carbon source and/or
      solubilizing agent on the aerobic biotransformation of a mixture of three common
      phytosterols (beta-sitosterol, stigmasterol and campesterol). The aerobic
      biotransformation of the phytosterol mixture by a mixed culture developed from a
      pulp and paper wastewater treatment system was examined under three separate
      conditions: with phytosterols as the sole added carbon source, with phytosterols
      and dextrin as an additional carbon source, and with phytosterols added with
      ethanol as an additional carbon source and solubilizing agent. Significant
      phytosterol removal was not observed in assays set up with phytosterol powder,
      either with or without an additional carbon source. In contrast, all three
      phytosterols were aerobically degraded when added as a dissolved solution in
      ethanol. Thus, under the experimental conditions of this study, the
      bioavailability of phytosterols was limited without the presence of a
      solubilizing agent. The total phytosterol removal rate was linear for the first
      six days before re-spiking, with a rate of 0.47 mg/L-d (R(2) = 0.998). After the
      second spiking, the total phytosterol removal rate was linear for seven days,
      with a rate of 0.32 mg/L-d (R(2) = 0.968). Following the 7th day, the phytosterol
      removal rate markedly accelerated, suggesting two different mechanisms are
      involved in phytosterol biotransformation, more likely related to the production
      of enzyme(s) involved in phytosterol degradation, induced under different cell
      growth conditions. beta-sitosterol was preferentially degraded, as compared to
      stigmasterol and campesterol, although all three phytosterols fell below
      detection limits by the 24th day of incubation. 

PMID- 24747139
TI  - Improving nitrogen removal in an ANAMMOX reactor using a permeable reactive
      biobarrier.
AB  - A novel ANAMMOX biofilm reactor that combines the advantages of conventional
      biofilm reactors and membrane bioreactors (MBRs) was developed in an attempt to
      decrease the levels of nitrogen in the reactor filtrate. In this reactor,
      nonwoven fabric modules served as both biofilm carriers and membrane-like
      separators, and the biofilm acted as a permeable reactive barrier for the removal
      of nitrogen species from the bulk liquid. Long-term monitoring suggests that the
      nitrogen removal rates (NRR) of the reactor reached ca. 1.6 kg-N/(m(3) d).
      Interestingly, large fractions of the ammonium (ca. 27%) and nitrite (ca. 48%)
      remaining in the bulk liquid were removed during their transport through the
      biofilm; thus, the reactive barrier process of the biofilm contributed ca. 11% to
      the total NRR. With an increase in the imposed flux, the contribution of the
      reactive barrier process to the removal of nitrogen from the reactor bulk liquid
      increased significantly, e.g., it contributed 26% to the NRR at 17.4 L/(m(2) h).
      Additionally, the nonwoven modules could retain free bacteria effectively; they
      maintained a non-fouling state during the entire operation period of
      approximately 400 days. Sequence analysis shows that Candidatus Kuenenia-like
      species dominated the ANAMMOX bacteria in the reactor. These results clearly
      demonstrate that this innovative reactor holds great promise for improving the
      ANAMMOX process, thus decreasing nitrogen levels in the effluent. 

PMID- 24747140
TI  - Greywater use in Israel and worldwide: standards and prospects.
AB  - Water shortage around the world enhanced the search for alternative sources.
      Greywater (GW) can serve as a solution for water demands especially in arid and
      semi-arid zones. However, issues considered which include acceptability of GW
      segregation as a separate water treated stream, allowing its use onsite.
      Consequently, it is the one of next forthcoming water resources that will be
      used, primarily in the growing mega-cities. It will be even more rentable when
      combined with the roof runoff water harvesting and condensing water from air
      conditioning systems. Reuse of GW is as well beneficial in the mega-cities
      subject to the high expenses associated with wastewater and fresh water
      conveyance in the opposite direction. The main problem associated with GW reuse
      is the quality of the water and the targeted reuse options. At least two main
      options can be identified: the public sector that is ready to reuse the GW and
      the private sector which raises extra issues related to the reuse risks. These
      risk stems from the on yard use of GW, relatively close to the household
      location. The main focus of the Israeli guidelines for GW use is on the private
      and single house. The problem is less rigorous in public facilities, where the
      amounts are relatively large and the raw GW is relatively diluted. The two main
      principles adopted for reuse are: (i) greywater can be minimally treated since it
      differs from the black wastes, and; (ii) no contact exists with the resident
      around. The aggravated standards are an indication of the sensitivity issues
      related to the problem. 

PMID- 24747141
TI  - Spatial and temporal evolution of organic foulant layers on reverse osmosis
      membranes in wastewater reuse applications.
AB  - Advanced treatment to remove trace constituents and emerging contaminants is an
      important consideration for wastewater treatment for potable reuse, and reverse
      osmosis (RO) can be a suitable technology to provide the necessary level of
      treatment. However, membrane fouling by biological and organic matter is a
      concern. This research examined the development of the RO membrane fouling layer
      using a bench-scale membrane bioreactor operating at different solids retention
      times (SRTs), followed by a custom-designed RO test cell. The RO test cell
      contained stacked plates that sandwich five sheets of RO membrane material, which
      can be extracted for autopsy at separate times over the course of an experiment
      without disturbing the remaining membranes. The MBR-RO system was run
      continuously for 2 weeks at each SRT. The RO membranes were stained for live and
      dead cells, protein, and carbohydrate-like materials, and visualized using
      confocal laser scanning microscopy. Images of the stained foulant layers were
      obtained at different depths within the foulant layer at each time point for all
      SRT conditions. As the RO foulant layer developed, changes occurred in the
      distribution and morphology of the live cells and carbohydrates, but not the
      proteins. These trends were similar for all three SRT conditions tested. RO
      membrane fouling increased with increased MBR SRT, and the highest SRT had the
      highest ratios of live to dead cells and carbohydrate-like material to dead
      cells. The autopsied membranes were also analyzed for protein and carbohydrate
      content, and it was found that the carbohydrate concentration on the membranes
      after 14 days increased as the SRT increased. 

PMID- 24747142
TI  - Oxygen mass transfer and hydrodynamic behaviour in wastewater: determination of
      local impact of surfactants by visualization techniques.
AB  - Powerful techniques, based on the Planar Laser Induced Fluorescence (PLIF)
      technique, are deployed to locally visualize and quantify the impact of
      surfactants in wastewaters on hydrodynamics and oxygen mass transfer. Bubble
      diameter, aspect ratio, rise velocity, contamination angle, as well as flux, flux
      density, liquid side mass transfer and diffusion coefficients of transferred
      oxygen are determined based on these techniques applied in the wake of rising
      bubbles of diameter 1 mm and through planar gas/liquid interfaces. The initial
      experiments were performed in demineralized water containing small amounts of
      surfactant. Different concentrations of surfactant were added to finally reach
      the Critical Micelle Concentration (CMC). Bubbles have classically been found to
      be more spherical with a reduced rise velocity in the presence of surfactants up
      to the CMC. Above the CMC, these hydrodynamic characteristics were found to be
      almost constant, although the oxygen mass transfer decreased due to the presence
      of surfactants. Experimental results were markedly lower than predicted by the
      well-known Frossling equation with rigid surfaces. This is believed to be caused
      by a barrier of surfactants hindering the oxygen mass transfer at the interface.
      Similar hindrance of oxygen mass transfer applies to waters from sewage plants
      (filtered raw water and treated water), making accurate design of aeration tanks
      difficult. 

PMID- 24747143
TI  - Surveillance of enteric viruses and coliphages in a tropical urban catchment.
AB  - An assessment of the occurrence and concentration of enteric viruses and
      coliphages was carried out in highly urbanized catchment waters in the tropical
      city-state of Singapore. Target enteric viruses in this study were noroviruses,
      adenoviruses, astroviruses and rotaviruses. In total, 65 water samples were
      collected from canals and the reservoir of the Marina catchment on a monthly
      basis over a period of a year. Quantitative PCR (qPCR) and single agar layer
      plaque assay (SAL) were used to enumerate target enteric viruses and coliphages
      in water samples, respectively. The most prevalent pathogen were noroviruses,
      detected in 37 samples (57%), particularly norovirus genogroup II (48%), with a
      mean concentration of 3.7 * 10(2) gene copies per liter. Rotavirus was the second
      most prevalent virus (40%) with a mean concentration of 2.5 * 10(2) GC/L. The
      mean concentrations of somatic and male-specific coliphages were 2.2 * 10(2) and
      1.1 * 10(2) PFU/100 ml, respectively. The occurrence and concentration of each
      target virus and the ratio of somatic to male-specific coliphages varied at
      different sampling sites in the catchment. For sampling sites with higher
      frequency of occurrence and concentration of viruses, the ratio of somatic to
      male-specific coliphages was generally much lower than other sampling sites with
      lower incidences of enteric viruses. Overall, higher statistical correlation was
      observed between target enteric viruses than between enteric viruses and
      coliphages. However, male-specific coliphages were positively correlated with
      norovirus concentrations. A multi-level integrated surveillance system, which
      comprises the monitoring of bacterial indicators, coliphages and selected enteric
      viruses, could help to meet recreational and surface water quality criteria in a
      complex urbanized catchment.

PMID- 24747144
TI  - Sexually dimorphic effects of prenatal exposure to propionic acid and
      lipopolysaccharide on social behavior in neonatal, adolescent, and adult rats:
      implications for autism spectrum disorders.
AB  - Emerging evidence suggests that the gut microbiome plays an important role in
      immune functioning, behavioral regulation and neurodevelopment. Altered
      microbiome composition, including altered short chain fatty acids, and/or immune
      system dysfunction, may contribute to neurodevelopmental disorders such as autism
      spectrum disorders (ASD), with some children with ASD exhibiting both abnormal
      gut bacterial metabolite composition and immune system dysfunction. This study
      describes the effects of prenatal propionic acid (PPA), a short chain fatty acid
      and metabolic product of many antibiotic resistant enteric bacteria, and of
      prenatal lipopolysaccharide (LPS), a bacterial mimetic and microbiome component,
      on social behavior in male and female neonatal, adolescent and adult rats.
      Pregnant Long-Evans rats were injected once a day with either a low level of PPA
      (500 mg/kg SC) on gestation days G12-16, LPS (50 MUg/kg SC) on G12, or vehicle
      control on G12 or G12-16. Sex- and age-specific, subtle effects on behavior were
      observed. Both male and female PPA treated pups were impaired in a test of their
      nest seeking response, suggesting impairment in olfactory-mediated neonatal
      social recognition. As well, adolescent males, born to PPA treated dams,
      approached a novel object more than control animals and showed increased levels
      of locomotor activity compared to prenatal PPA females. Prenatal LPS produced
      subtle impairments in social behavior in adult male and female rats. These
      findings raise the possibility that brief prenatal exposure to elevated levels of
      microbiome products, such as PPA or LPS, can subtly influence neonatal,
      adolescent and adult social behavior.

PMID- 24747145
TI  - Cerebral microdialysis in glioma studies, from theory to application.
AB  - Despite recent advances in the treatment of solid tumors, there are few effective
      treatments for malignant gliomas due to the infiltrative nature, and the
      protective shield of blood-brain barrier or blood-tumor barriers that restrict
      the passage of chemotherapy drugs into the brain. Imaging techniques, such as PET
      and MRI, have allowed the assessment of tumor function in vivo, but they are
      indirect measures of activity and do not easily allow continuous repeated
      evaluations. Because the biology of glioma on a cellular and molecular level is
      fairly unknown, especially in relation to various treatments, the development of
      novel therapeutic approaches to this devastating condition requires a strong need
      for a deeper understanding of the tumor's pathophysiology and biochemistry.
      Cerebral microdialysis, a probe-based sampling technique, allows a discrete
      volume of the brain to be sampled for neurochemical analysis of
      neurotransmitters, metabolites, biomarkers, and chemotherapy drugs, which has
      been employed in studying brain tumors, and is significant for improving the
      treatment of glioma. In this review, the current concepts of cerebral
      microdialysis for glioma are elucidated, with a special emphasis on its
      application to neurochemistry and pharmacokinetic studies. 

PMID- 24747146
TI  - Development of a surface display ELISA to detect anti-IgG antibodies against
      bovine alphaS1-casein in human sera.
AB  - The aim of the present study was to develop a surface display ELISA (SD-ELISA)
      for IgG-serum reaction against bovine casein alphaS1 (CSN1S1). In a SD-ELISA, the
      antigen is displayed on the surface of Escherichia coli using the autodisplay
      technology and whole cells of E. coli are used to coat the microplates for serum
      testing. After establishing the setup of the SD-ELISA with polyclonal rabbit
      antiserum against bovine CSN1S1, the SD-ELISA was validated with 20 human sera,
      of which 10 sera were proven to have an IgG-mediated reaction against bovine
      CSN1S1 and 10 sera were shown to be negative for this reaction. Receiver
      operating characteristics (ROC) analysis revealed sensitivity of 100% and a
      specificity of 100% at a cut-off value of 0.133. Furthermore, human serum of 48
      patients with known reactivity against human CSN1S1 (31 positive and 17 negative)
      was examined by the newly developed SD-ELISA to exclude cross-reactivity. Twenty
      human sera showed an IgG-mediated reaction against bovine CSN1S1. Eleven of these
      sera were positive for the reactivity against human CSN1S1, and nine were
      negative. In conclusion it was demonstrated that the performance of SD-ELISA is
      comparable to established ELISA without loss in sensitivity or specificity. Based
      on the advantages of this method - in particular no need for time-consuming and
      expensive antigen production and purification - the SD-ELISA is a potent
      alternative to convenient methods for identification and especially high
      throughput screening of new antigens in the field of food allergies. 

PMID- 24747147
TI  - Determination of a novel carbamate AChE inhibitor meserine in mouse plasma, brain
      and rat plasma by LC-MS/MS: application to pharmacokinetic study after
      intravenous and subcutaneous administration.
AB  - In this paper a simple and sensitive method for determination of a novel
      phenylcarbamate AChE inhibitor, meserine, in mouse plasma, brain and rat plasma
      was evaluated using high-performance liquid chromatography-tandem mass
      spectrometry (LC-MS/MS). Separation was achieved on an Alltech Alltima-C18 column
      (150mm*2.1mm, 3MUm, Deerfield, IL, USA) with isocratic elution at a flow rate of
      0.35ml/min. Detection was performed under the multiple reaction monitoring (MRM)
      mode using an electrospray ionization (ESI) in the positive ion mode. The protein
      precipitation and liquid-liquid extraction methods were used for the pretreatment
      of plasma and brain homogenates, respectively. The calibration curves of meserine
      showed good linearity over the concentration range of 0.5-1000ng/ml for mouse and
      rat plasma and 0.5-500ng/ml for mouse brain. The intra- and inter-day precision
      were less than 9.34% and the accuracy was from 95.34% to 107.78% for QC samples.
      The validated method was successfully applied to a preclinical pharmacokinetic
      study of meserine in mice and rats after intravenous and subcutaneous
      administration. The results showed that this novel drug could easily cross the
      blood-brain barrier to reach the site of drug action. Meserine was rapidly
      absorbed with a high subcutaneous absolute bioavailability (>90%). 

PMID- 24747148
TI  - Characterization of Sildenafil analogs by MS/MS and NMR: a guidance for detection
      and structure elucidation of phosphodiesterase-5 inhibitors.
AB  - Novel synthetic analogs of Sildenafil are constantly detected as adulterants in
      counterfeit drugs and dietary supplements. Their intake constitutes a serious
      health hazard as side effects are unknown. In this paper an investigation is
      carried out on NMR and MS/MS spectra of Sildenafil, Thiosildenafil, Acetildenafil
      and thirteen of their analogs: a list of key signals is reported and discussed
      with the intent to provide a tool that can help in detecting adulteration and in
      elucidating the structure of novel analogs. In this view extensive spectral data
      were reported, discussed and summarized in tables. A discussion on mass
      fragmentation and NMR chemical shifts is also provided to rationalize
      assignation. Moreover, a comprehensive information on the route of synthesis is
      provided for the benefit of those medicines control laboratories that need to
      synthesize analogs reference standards in-house. 

PMID- 24747149
TI  - PURE ribosome display and its application in antibody technology.
AB  - Ribosome display utilizes formation of the mRNA-ribosome-polypeptide ternary
      complex in a cell-free protein synthesis system to link genotype (mRNA) to
      phenotype (polypeptide). However, the presence of intrinsic components, such as
      nucleases in the cell-extract-based cell-free protein synthesis system, reduces
      the stability of the ternary complex, which would prevent attainment of reliable
      results. We have developed an efficient and highly controllable ribosome display
      system using the PURE (Protein synthesis Using Recombinant Elements) system. The
      mRNA-ribosome-polypeptide ternary complex is highly stable in the PURE system,
      and the selected mRNA can be easily recovered because activities of nucleases and
      other inhibitory factors are very low in the PURE system. We have applied the
      PURE ribosome display to antibody engineering approaches, such as epitope mapping
      and affinity maturation of antibodies, and obtained results showing that the PURE
      ribosome display is more efficient than the conventional method. We believe that
      the PURE ribosome display can contribute to the development of useful antibodies.
      This article is part of a Special Issue entitled: Recent advances in molecular
      engineering of antibody.

PMID- 24747150
TI  - Molecular recognition of Cullin3 by KCTDs: insights from experimental and
      computational investigations.
AB  - Recent investigations have highlighted a key role of the proteins of the KCTD (K
      potassium channel tetramerization domain containing proteins) family in several
      fundamental biological processes. Despite the growing importance of KCTDs, our
      current understanding of their biophysical and structural properties is very
      limited. Biochemical characterizations of these proteins have shown that most of
      them act as substrate adaptor in E3 ligases during protein ubiquitination. Here
      we present a characterization of the KCTD5-Cullin3 interactions which are
      mediated by the KCTD5 BTB domain. Isothermal titration calorimetry experiments
      reveal that KCTD5 avidly binds the Cullin3 (Cul3). The complex presents a 5:5
      stoichiometry and a dissociation constant of 59 nM. Molecular modeling and
      molecular dynamics simulations clearly indicate that the two proteins form a
      stable (KCTD5-Cul3)(5) pinwheel-shaped heterodecamer in which two distinct KCTD5
      subunits cooperate in the binding of each cullin chain. Molecular dynamics
      simulations indicate that different types of interactions contribute to the
      stability of the assembly. Interestingly, residues involved in Cul3 recognitions
      are conserved in the KCTD5 orthologs and paralogs implicated in important
      biological processes. These residues are also rather well preserved in most of
      the other KCTD proteins. By using molecular modeling techniques, the entire
      ubiquitination system including the E3 ligase, the E2 conjugating enzyme and
      ubiquitin was generated. The analysis of the molecular architecture of this
      complex machinery provides insights into the ubiquitination processes which
      involve E3 ligases with a high structural complexity.

PMID- 24747151
TI  - Development of a cell-based assay system considering drug metabolism and immune-
      and inflammatory-related factors for the risk assessment of drug-induced liver
      injury.
AB  - Drug-induced liver injury (DILI) is a major safety concern in drug development
      and clinical pharmacotherapy. However, prediction of DILI is difficult because
      the underlying mechanisms are not fully understood. To establish a novel cell
      based screening system to suggest drugs with hepatotoxic potential in preclinical
      drug development, comprehensive gene expression analyses during in vivo DILI are
      necessary. Using in vivo mouse DILI models and 4 sets of hepatotoxic positive and
      non-hepatotoxic drugs, we found that the hepatic mRNA levels of S100A8; S100A9;
      "NATCH, LRR, and pyrin domain-containing protein 3" (NALP3); interleukin (IL)
      1beta; and the receptor for advanced glycation endproducts (RAGE) were commonly
      increased in hepatotoxic drug-administered mice compared to non-hepatotoxic drug
      administered mice. To clarify whether these 5 in vivo biomarkers can be applied
      to a cell-based screening system, we adapted human liver microsomes (HLM) in the
      presence of NADPH to assess the metabolic activation reaction, and we also
      adapted human monocytic leukemia cells HL-60, K562, KG-1 and THP-1 to assess the
      effects on mRNA expression of immune- and inflammatory-related factors. We
      investigated 30 clinical drugs with different safety profiles with regard to DILI
      and found that the total sum score of gene expression levels of S100A8, S100A9,
      RAGE, NALP3 and IL-1beta mRNA in HL-60 or K562 cells incubated with HLM, could
      identify drugs at high risk for hepatotoxicity. We proposed the use of the total
      sum score of gene expression level for assessing metabolic activation by drug
      metabolizing enzymes and immune- and inflammatory-related factors for the risk
      assessment of DILI in preclinical drug development. 

PMID- 24747152
TI  - Procalcitonin use in a pediatric intensive care unit.
AB  - We evaluated whether procalcitonin (PCT) might aid diagnosing serious bacterial
      infections in a general pediatric intensive care unit population. Two-hundred and
      one patients accounted for 332 PCT samples. A PCT >=1.45 ng/mL had a positive
      predictive value of 30%, a negative predictive value of 93% and a sensitivity of
      72% and a specificity of 75%. These data suggest PCT can assist in identifying
      patients without serious bacterial infections and limit antimicrobial use. 

PMID- 24747153
TI  - Once-daily antiretroviral therapy in a cohort of HIV-infected children and
      adolescents.
AB  - We evaluated the evolution over time of once-daily antiretroviral therapy in HIV
      infected children and its relationship with adherence. An increase on the
      prevalence of once-daily antiretroviral therapy was observed over time (from 0.9%
      in 2002 to 44.2% in 2011). There was no difference in adherence regarding once
      daily or BID regimens in 2011. Adherence was related to age and pill burden. 

PMID- 24747154
TI  - Does desire for hastened death change in terminally ill cancer patients?
AB  - Understanding why some terminally ill patients may seek a hastened death (a
      construct referred to as "desire for hastened death" or DHD) is critical to
      understanding how to optimize quality of life during an individual's final weeks,
      months or even years of life. Although a number of predictor variables have
      emerged in past DHD research, there is a dearth of longitudinal research on how
      DHD changes over time and what factors might explain such changes. This study
      examined DHD over time in a sample of terminally ill cancer patients admitted to
      a palliative care hospital. A random sample of 128 patients completed the
      Schedule of Attitudes toward Hastened Death (SAHD) at two time points
      approximately 2-4 weeks apart participated. Patients were categorized into one of
      four trajectories based on their SAHD scores at both time points: low (low DHD at
      T1 and T2), rising (low DHD at T1 and high DHD at T2), falling (high DHD at T1
      and low DHD at T2) and high (high DHD at T1 and T2). Among patients who were low
      at T1, several variables distinguished between those who developed DHD and those
      who did not: physical symptom distress, depression symptom severity,
      hopelessness, spiritual well-being, baseline DHD, and a history of mental health
      treatment. However, these same medical and clinical variables did not distinguish
      between the falling and high trajectories. Overall, there appears to be a
      relatively high frequency of change in DHD, even in the last weeks of life.
      Interventions designed to target patients who are exhibiting subthreshold DHD and
      feelings of hopelessness may reduce the occurrence of DHD emerging in this
      population.

PMID- 24747155
TI  - Comment on the 2013 ACC/AHA guidelines on Lifestyle Management to Reduce
      Cardiovascular Risk by the JAS Guidelines Committee.

PMID- 24747156
TI  - An affordable HIV-1 drug resistance monitoring method for resource limited
      settings.
AB  - HIV-1 drug resistance has the potential to seriously compromise the effectiveness
      and impact of antiretroviral therapy (ART). As ART programs in sub-Saharan Africa
      continue to expand, individuals on ART should be closely monitored for the
      emergence of drug resistance. Surveillance of transmitted drug resistance to
      track transmission of viral strains already resistant to ART is also critical.
      Unfortunately, drug resistance testing is still not readily accessible in
      resource limited settings, because genotyping is expensive and requires
      sophisticated laboratory and data management infrastructure. An open access
      genotypic drug resistance monitoring method to manage individuals and assess
      transmitted drug resistance is described. The method uses free open source
      software for the interpretation of drug resistance patterns and the generation of
      individual patient reports. The genotyping protocol has an amplification rate of
      greater than 95% for plasma samples with a viral load >1,000 HIV-1 RNA copies/ml.
      The sensitivity decreases significantly for viral loads <1,000 HIV-1 RNA
      copies/ml. The method described here was validated against a method of HIV-1 drug
      resistance testing approved by the United States Food and Drug Administration
      (FDA), the Viroseq genotyping method. Limitations of the method described here
      include the fact that it is not automated and that it also failed to amplify the
      circulating recombinant form CRF02_AG from a validation panel of samples,
      although it amplified subtypes A and B from the same panel. 

PMID- 24747157
TI  - The effects of information type (features vs. configuration) and location (eyes
      vs. mouth) on the development of face perception.
AB  - The goal of the current study was to investigate the development of face
      processing strategies in a perceptual discrimination task. Children (7-12 years
      of age) and young adults were administered the Face Dimensions Task. In the Face
      Dimensions Task, participants were asked to judge whether two simultaneously
      presented faces were the "same" or "different". For the "same" trials, the two
      faces were identical. For the "different" trials, the faces differed in either
      the spacing between the eyes, the spacing between the nose and the mouth, the
      size of the eyes, or the size of the mouth. The main finding was that 7- to 10
      year-old children showed no difference in their ability to discriminate
      differences in eye size and eye spacing but showed a poor ability to discriminate
      differences in nose and mouth spacing and, to a lesser extent, mouth size. The
      developmental lag between nose-mouth discriminations and the other featural and
      configural discriminations was reduced in older children and eliminated by young
      adulthood. These results indicate that the type of face information (i.e.,
      configural vs. featural) and its location (i.e., eye vs. mouth) jointly
      contribute to the development of face perception abilities.

PMID- 24747158
TI  - Development, validation and clinical application of a HPLC-FL method for CYP2D6
      phenotyping in South Brazilian breast cancer patients.
AB  - OBJECTIVE: To develop and validate a method for determination of dextromethorphan
      (DMT) and dextrorphan (DTP) in plasma samples using HPLC-FL and to apply it to
      CYP2D6 phenotyping of a population from the South of Brazil. METHODS: Samples
      were prepared by hydrolysis and liquid-liquid extraction. Analysis was conducted
      in a reversed phase column, with isocratic elution and fluorescence detection.
      One hundred and forty patients being treated with tamoxifen were given 30 mg of
      dextromethorphan and their CYP2D6 phenotypes were determined on the basis of
      [DMT]/[DTP] metabolic ratios in plasma samples collected after 3h. RESULTS: Total
      chromatography running time was 12 min. Precision (CV%) was below 9.7% and
      accuracy was between 92.1 and 106.9%. The lower limits of quantification were 1
      ng mL(-1) for DMT and 10 ng mL(-1) for DTP. Mean extraction yield of analytes was
      86.6%. Mean age of patients was 55.7 years. Phenotype frequencies were as
      follows: 7.1% poor metabolizers, 13.6% intermediate metabolizers, 77.1% extensive
      metabolizers and 2.1 ultra-rapid metabolizers. Metabolic ratios for patients on
      strong (n=11) and weak (n=16) CYP2D6 activity inhibitors were different from each
      other and also different from ratios for patients not taking enzyme inhibitors
      (n=113). CONCLUSIONS: A sensitive method for determination of dextromethorphan
      and its metabolite in plasma samples was developed and successfully applied,
      providing evidence of the impact that CYP2D6 inhibitors have on the enzyme's
      metabolic capacity.

PMID- 24747159
TI  - Interleukin-1beta genotype and circulating levels in cancer patients: metastatic
      status and pain perception.
AB  - OBJECTIVES: Proinflammatory cytokines released during inflammation can cause
      hyperexcitability in pain transmission neurons, leading to hyperalgesia and
      allodynia. Polymorphisms in interleukin 1 (IL-1) family of genes (IL1A, IL1B) and
      in IL-1 receptor antagonist (IL-1Ra, coded by IL1RN) may therefore induce
      alterations in cytokine levels/effects and pain related response. Our purpose was
      to investigate the influence of polymorphisms in IL1A/B/RN on cytokine serum
      levels and its correlation with pain intensity, performance status, adverse
      effects, metastases and breakthrough pain in Caucasian cancer patients. DESIGN
      AND METHODS: Serum IL-1alpha/beta levels of 74 cancer patients were measured by
      competitive enzyme immunosorbent assay. All patients were also genotyped for the
      polymorphisms in IL1A (rs17561), IL1B (rs1143634) and IL1RN (rs419598) with Real
      Time PCR. Results were then correlated to the appearance of bone or CNS
      metastases and several pain-related parameters. RESULTS: IL-1beta rs1143634
      homozygous for T allele were associated with lower levels of IL1-beta (p=0.032,
      Mann-Whitney test) and presented a trend for lower levels of pain (p=0.06,
      Fisher's Exact Test). Also, IL1-beta levels were related with cancer onset
      status, since a four-fold increase probability of metastatic disease was observed
      in high IL-1beta individuals (OR=4.074, p=0.010, Pearson chi(2) test). Among the
      female patients presenting metastatic disease and carriers of the TT genotype we
      observed a trend to lower levels of IL1-beta (p=0.053, Pearson chi(2) test).
      CONCLUSIONS: Our results indicate that genetic variation at IL1-beta gene may
      influence serum levels of IL1-beta, with proportional consequences in cancer
      related pain.

PMID- 24747160
TI  - An overview of clinical and commercial impact of drug delivery systems.
AB  - Drug delivery systems are widely researched and developed to improve the delivery
      of pharmaceutical compounds and molecules. The last few decades have seen a
      marked growth of the field fueled by increased number of researchers, research
      funding, venture capital and the number of start-ups. Collectively, the growth
      has led to novel systems that make use of micro/nano-particles, transdermal
      patches, inhalers, drug reservoir implants and antibody-drug conjugates. While
      the increased research activity is clearly an indication of proliferation of the
      field, clinical and commercial translation of early-stage research ideas is
      critically important for future growth and interest in the field. Here, we will
      highlight some of the examples of novel drug delivery systems that have undergone
      such translation. Specifically, we will discuss the developments, advantages,
      limitations and lessons learned from: (i) microparticle-based depot formulations,
      (ii) nanoparticle-based cancer drugs, (iii) transdermal systems, (iv) oral drug
      delivery systems, (v) pulmonary drug delivery, (vi) implants and (vii) antibody
      drug conjugates. These systems have impacted treatment of many prevalent diseases
      including diabetes, cancer and cardiovascular diseases, among others. At the same
      time, these systems are integral and enabling components of products that
      collectively generate annual revenues exceeding US $100 billion. These examples
      provide strong evidence of the clinical and commercial impact of drug delivery
      systems.

PMID- 24747161
TI  - Cell-mediated delivery of nanoparticles: taking advantage of circulatory cells to
      target nanoparticles.
AB  - Cellular hitchhiking leverages the use of circulatory cells to enhance the
      biological outcome of nanoparticle drug delivery systems, which often suffer from
      poor circulation time and limited targeting. Cellular hitchhiking utilizes the
      natural abilities of circulatory cells to: (i) navigate the vasculature while
      avoiding immune system clearance, (ii) remain relatively inert until needed and
      (iii) perform specific functions, including nutrient delivery to tissues,
      clearance of pathogens, and immune system surveillance. A variety of synthetic
      nanoparticles attempt to mimic these functional attributes of circulatory cells
      for drug delivery purposes. By combining the advantages of circulatory cells and
      synthetic nanoparticles, many advanced drug delivery systems have been developed
      that adopt the concept of cellular hitchhiking. Here, we review the development
      and specific applications of cellular hitchhiking-based drug delivery systems. 

PMID- 24747163
TI  - Vam3, a resveratrol dimer, inhibits cigarette smoke-induced cell apoptosis in
      lungs by improving mitochondrial function.
AB  - AIM: To investigate the effects of Vam3 (a resveratrol dimer extracted from Vitis
      amurensis Rupr) on cigarette smoke (CS)-induced cell apoptosis in lungs in vitro
      and in vivo and the underlying mechanisms of action. METHODS: Human bronchial
      epithelial cell line BEAS-2B was exposed to cigarette smoke condensate (CSC, 300
      mg/L), and cell apoptosis was determined using flow cytometry and Hoechst
      staining. Mitochondrial membrane potential was examined with TMRE staining. ROS
      and ceramide levels were detected with DCFH-DA fluorescence and HPLC-MS/MS,
      respectively. Cytochrome c release was detected using immunofluorescence. Caspase
      9 and neutral sphingomyelinase 2 expression was measured with Western blotting.
      The breast carcinoma cell line MCF7 stably expressing GFP-tagged Bax was used to
      elucidate the role of mitochondria in CS-induced apoptosis. For in vivo study,
      male mice were exposed to CS for 5 min twice a day for 4 weeks. The mice were
      orally administered Vam3 (50 mg.kg(-1).d(-1)) or resveratrol (30 mg.kg(-1).d(-1))
      each day 1 h before the first CS exposure. RESULTS: Pretreatment of BEAS-2B cells
      with Vam3 (5 MUmol/L) or resveratrol (5 MUmol/L) significantly suppressed CSC
      induced apoptosis, and prevented CSC-induced Bax level increase in the
      mitochondria, mitochondrial membrane potential loss, cytochrome c release and
      caspase-9 activation. Furthermore, pretreatment of BEAS-2B cells with Vam3 or
      resveratrol significantly suppressed CSC-stimulated intracellular ceramide
      production, and CSC-induced upregulation of neutral sphingomyelinase 2, the
      enzyme responsible for ceramide production in bronchial epithelial cells. Similar
      results were obtained in C6-pyridinium ceramide-induced apoptosis of GFP-Bax
      stable MCF7 cells in vitro, and in the lungs of CS-exposed mice that were treated
      with oral administration of Vam3 or resveratrol. CONCLUSION: Vam3 protects
      bronchial epithelial cells from CS-induced apoptosis in vitro and in vivo by
      preventing mitochondrial dysfunction.

PMID- 24747162
TI  - Macromolecular therapeutics.
AB  - This review covers water-soluble polymer-drug conjugates and macromolecules that
      possess biological activity without attached low molecular weight drugs. The main
      design principles of traditional and backbone degradable polymer-drug conjugates
      as well as the development of a new paradigm in nanomedicines - (low molecular
      weight) drug-free macromolecular therapeutics are discussed. To address the
      biological features of cancer, macromolecular therapeutics directed to
      stem/progenitor cells and the tumor microenvironment are deliberated. Finally,
      the future perspectives of the field are briefly debated. 

PMID- 24747164
TI  - Cyclovirobuxinum D suppresses lipopolysaccharide-induced inflammatory responses
      in murine macrophages in vitro by blocking JAK-STAT signaling pathway.
AB  - AIM: Cyclovirobuxinum D (CVB-D), an alkaloid isolated from the Chinese medicinal
      plant Buxus microphylla, has been found to be effective to treat cardiac
      insufficiency, arrhythmias and coronary heart disease. In the present study, we
      investigated the effects of CVB-D on the inflammatory responses in
      lipopolysaccharide (LPS)-stimulated murine macrophages in vitro and the
      underlying mechanisms. METHODS: Murine macrophage cell line RAW264.7 cells were
      incubated in the presence of LPS (0.1 MUg/mL) for 24 h. The cell viability was
      measured using MTT assay. The release of NO and cytokines were detected using the
      Griess test and ELISA, respectively. The mRNA and protein levels were determined
      using RT-PCR and Western blot, respectively. Reporter gene assays were used to
      analyze the transcriptional activity of NF-kappaB. RESULTS: Treatment of RAW264.7
      cells with CVB-D (25-300 MUmol/L) did not affect the cell viability. Pretreatment
      with CVB-D (50, 100 and 200 MUmol/L) concentration-dependently decreased NO
      release and iNOS expression in LPS-treated RAW264.7 cells (its IC50 value in
      inhibition of NO production was 144 MUmol/L). CVB-D also concentration
      dependently inhibited the secretion and mRNA expression of IL-1beta and IL-6 in
      LPS-treated RAW264.7 cells. Furthermore, CVB-D remarkably inhibited the
      phosphorylation of STAT1 and STAT3, as well as JAK2 in LPS-treated RAW264.7
      cells, but did not affect the activation of NF-kappaB and MAPKs pathways.
      Pretreatment with the JAK2 specific inhibitor AG490 (30 MUmol/L) produced similar
      effects on NO release and iNOS expression in LPS-treated RAW264.7 cells.
      CONCLUSION: CVB-D exerts anti-inflammatory effects in LPS-stimulated murine
      macrophages in vitro at least in part by blocking the JAK-STAT signaling pathway.
      The anti-inflammatory actions of CVB-D may contribute to its cardioprotection.

PMID- 24747166
TI  - In vivo electrophysiological measurements on mouse sciatic nerves.
AB  - Electrophysiological studies allow a rational classification of various
      neuromuscular diseases and are of help, together with neuropathological
      techniques, in the understanding of the underlying pathophysiology(1). Here we
      describe a method to perform electrophysiological studies on mouse sciatic nerves
      in vivo. The animals are anesthetized with isoflurane in order to ensure
      analgesia for the tested mice and undisturbed working environment during the
      measurements that take about 30 min/animal. A constant body temperature of 37 
      degrees C is maintained by a heating plate and continuously measured by a rectal
      thermo probe(2). Additionally, an electrocardiogram (ECG) is routinely recorded
      during the measurements in order to continuously monitor the physiological state
      of the investigated animals. Electrophysiological recordings are performed on the
      sciatic nerve, the largest nerve of the peripheral nervous system (PNS),
      supplying the mouse hind limb with both motoric and sensory fiber tracts. In our
      protocol, sciatic nerves remain in situ and therefore do not have to be extracted
      or exposed, allowing measurements without any adverse nerve irritations along
      with actual recordings. Using appropriate needle electrodes(3) we perform both
      proximal and distal nerve stimulations, registering the transmitted potentials
      with sensing electrodes at gastrocnemius muscles. After data processing, reliable
      and highly consistent values for the nerve conduction velocity (NCV) and the
      compound motor action potential (CMAP), the key parameters for quantification of
      gross peripheral nerve functioning, can be achieved. 

PMID- 24747165
TI  - Hydrogen sulfide inhibits homocysteine-induced endoplasmic reticulum stress and
      neuronal apoptosis in rat hippocampus via upregulation of the BDNF-TrkB pathway.
AB  - AIM: Homocysteine (Hcy) can elicit neuronal cell death, and hyperhomocysteinemia
      is a strong independent risk factor for Alzheimer's disease. The aim of this
      study was to examine the effects of hydrogen sulfide (H2S) on Hcy-induced
      endoplasmic reticulum (ER) stress and neuronal apoptosis in rat hippocampus.
      METHODS: Adult male SD rats were intracerebroventricularly (icv) injected with
      Hcy (0.6 MUmol/d) for 7 d. Before Hcy injection, the rats were treated with NaHS
      (30 or 100 MUmol.kg(-1).d(-1), ip) and/or k252a (1 MUg/d, icv) for 2 d. The
      apoptotic neurons were detected in hippocampal coronal slices with TUNEL
      staining. The expression of glucose regulated protein 78 (GRP78), C/EBP
      homologous protein (CHOP), cleaved caspase-12, and BDNF in the hippocampus were
      examined using Western blotting assays. The generation of H2S in the hippocampus
      was measured with the NNDPD method. RESULTS: Hcy markedly inhibited the
      production of endogenous H2S and increased apoptotic neurons in the hippocampus.
      Furthermore, Hcy induced ER stress responses in the hippocampus, as indicated by
      the upregulation of GRP78, CHOP, and cleaved caspase-12. Treatment with the H2S
      donor NaHS increased the endogenous H2S production and BDNF expression in a dose
      dependent manner, and significantly reduced Hcy-induced neuronal apoptosis and ER
      stress responses in the hippocampus. Treatment with k252a, a specific inhibitor
      of TrkB (the receptor of BDNF), abolished the protective effects of NaHS against
      Hcy-induced ER stress in the hippocampus. CONCLUSION: H2S attenuates ER stress
      and neuronal apoptosis in the hippocampus of Hcy-treated rats via upregulating
      the BDNF-TrkB pathway.

PMID- 24747167
TI  - Don't believe what you read (only once): comprehension is supported by
      regressions during reading.
AB  - Recent Web apps have spurred excitement around the prospect of achieving speed
      reading by eliminating eye movements (i.e., with rapid serial visual
      presentation, or RSVP, in which words are presented briefly one at a time and
      sequentially). Our experiment using a novel trailing-mask paradigm contradicts
      these claims. Subjects read normally or while the display of text was manipulated
      such that each word was masked once the reader's eyes moved past it. This
      manipulation created a scenario similar to RSVP: The reader could read each word
      only once; regressions (i.e., rereadings of words), which are a natural part of
      the reading process, were functionally eliminated. Crucially, the inability to
      regress affected comprehension negatively. Furthermore, this effect was not
      confined to ambiguous sentences. These data suggest that regressions contribute
      to the ability to understand what one has read and call into question the
      viability of speed-reading apps that eliminate eye movements (e.g., those that
      use RSVP). 

PMID- 24747168
TI  - The dopamine D4 receptor gene (DRD4) moderates cultural difference in independent
      versus interdependent social orientation.
AB  - Prior research suggests that cultural groups vary on an overarching dimension of
      independent versus interdependent social orientation, with European Americans
      being more independent, or less interdependent, than Asians. Drawing on recent
      evidence suggesting that the dopamine D4 receptor gene (DRD4) plays a role in
      modulating cultural learning, we predicted that carriers of DRD4 polymorphisms
      linked to increased dopamine signaling (7- or 2-repeat alleles) would show higher
      levels of culturally dominant social orientations, compared with noncarriers.
      European Americans and Asian-born Asians (total N = 398) reported their social
      orientation on multiple scales. They were also genotyped for DRD4. As in earlier
      work, European Americans were more independent, and Asian-born Asians more
      interdependent. This cultural difference was significantly more pronounced for
      carriers of the 7- or 2-repeat alleles than for noncarriers. Indeed, no cultural
      difference was apparent among the noncarriers. Implications for potential
      coevolution of genes and culture are discussed. 

PMID- 24747169
TI  - Justifying atrocities: the effect of moral-disengagement strategies on socially
      shared retrieval-induced forgetting.
AB  - A burgeoning literature has established that exposure to atrocities committed by
      in-group members triggers moral-disengagement strategies. There is little
      research, however, on how such moral disengagement affects the degree to which
      conversations shape people's memories of the atrocities and subsequent
      justifications for those atrocities. We built on the finding that a speaker's
      selective recounting of past events can result in retrieval-induced forgetting of
      related, unretrieved memories for both the speaker and the listener. In the
      present study, we investigated whether American participants listening to the
      selective remembering of atrocities committed by American soldiers (in-group
      condition) or Afghan soldiers (out-group condition) resulted in the retrieval
      induced forgetting of unmentioned justifications. Consistent with a motivated
      recall account, results showed that the way people's memories are shaped by
      selective discussions of atrocities depends on group-membership status. 

PMID- 24747170
TI  - The regulation of mitochondrial dynamics.
AB  - The structure of mitochondria is highly dynamic. Mitochondrial shape is cell-type
      specific and can be modified to meet changing requirements in energy production,
      calcium homeostasis, lipid biogenesis, fatty acid synthesis and other
      mitochondrial activities. This is achieved by modulating the dynamic properties
      of mitochondria including fusion, division, movement and positional tethering. It
      has become increasingly evident that mitochondrial dynamics also play an intimate
      role in several cellular signaling pathways and as such, many mechanisms have
      evolved to modulate mitochondrial structure. These regulatory mechanisms turn out
      to be important for modulation of mitochondrial-specific processes as well as
      cell, tissue and organism responses to developmental or environmental cues. 

PMID- 24747172
TI  - Personalized busulfan and treosulfan conditioning for pediatric stem cell
      transplantation: the role of pharmacogenetics and pharmacokinetics.
AB  - Busulfan- and treosulfan-based conditionings are the cornerstone of pediatric
      allogeneic hematopoietic stem cell transplantation (HSCT). Although both drugs
      are alkylating agents, their mechanisms of action, pharmacokinetics (PK) and
      toxicity profiles are different. Experience with busulfan in pediatric HSCT is
      broad and the knowledge on the pharmacodynamics (PD), PK and, to a lesser extent,
      pharmacogenetics (PG) has resulted in a more effective therapy. Treosulfan has
      only recently been introduced in pediatric HSCT and is considered a promising new
      therapy because of its beneficial toxicity profile. However, knowledge of the PK
      and PG of treosulfan is limited. In this review, we describe the pharmacology of
      both agents and discuss factors causing variability in PK in relation to
      therapeutic outcome in HSCT. 

PMID- 24747171
TI  - Mechanisms shaping cell membranes.
AB  - Membranes of intracellular organelles are characterized by large curvatures with
      radii of the order of 10-30nm. While, generally, membrane curvature can be a
      consequence of any asymmetry between the membrane monolayers, generation of large
      curvatures requires the action of mechanisms based on specialized proteins. Here
      we discuss the three most relevant classes of such mechanisms with emphasis on
      the physical requirements for proteins to be effective in generation of membrane
      curvature. We provide new quantitative estimates of membrane bending by shallow
      hydrophobic insertions and compare the efficiency of the insertion mechanism with
      those of the protein scaffolding and crowding mechanisms. 

PMID- 24747173
TI  - The role of ANK interactions with MYBBP1a and SPHK1 in catabolic events of
      articular chondrocytes.
AB  - OBJECTIVE: To determine the role of progressive ankylosis protein (ANK)/Myb
      binding protein 1a (MYBBP1a) and sphingosine kinase 1 (SPHK1) interactions in
      catabolic events of articular chondrocytes. METHOD: ANK/MYBBP1a and SPHK1
      interactions were identified using yeast two-hybrid screening and co
      immunoprecipitation. To determine the role of these interactions in catabolic
      events of articular chondrocytes, ank/ank and wild type (WT) mouse chondrocytes
      transfected with full-length or mutant ank expression vectors (EVs) or femoral
      heads were treated with interleukin-1beta (IL-1beta) in the absence or presence
      of SPHK inhibitor. Catabolic marker mRNA levels were analyzed by real time PCR;
      proteoglycan loss using safranin O staining and MMP-13 immunostaining were
      determined in femoral head explants; NF-kappaB activity was determined by
      transfecting chondrocytes with an NF-kappaB-specific luciferase reporter and
      analyzing nuclear translocation of p65 by immunoblotting; MYBBP1a nuclear or
      cytoplasmic amounts were determined by immunohistochemistry and immunoblotting.
      RESULTS: The ANK N-terminal region interacted with SPHK1, whereas a cytoplasmic C
      terminal loop interacted with MYBBP1a. Lack of ANK/MYBBP1a and SPHK1 interactions
      in ank/ank chondrocytes resulted in increased MYBBP1a nuclear amounts and
      decreased SPHK1 activity, and consequently decreased NF-kappaB activity,
      catabolic marker mRNA levels, proteoglycan loss, and MMP-13 immunostaining in IL
      1beta-treated articular chondrocytes or femoral heads. Transfection with full
      length ank EV reduced nuclear MYBBP1a amounts and fully restored SPHK and NF
      kappaB activities in IL-1beta-treated ank/ank chondrocytes, whereas transfection
      with P5L or F376del mutant ank reduced nuclear MYBBP1a or increased SPHK
      activity, respectively, and consequently either transfection only partially
      restored NF-kappaB activity. CONCLUSION: ANK/MYBBP1a and SPHK1 interactions
      stimulate catabolic events in IL-1beta-mediated cartilage degradation.

PMID- 24747174
TI  - In vivo imaging of MMP-13 activity in the murine destabilised medial meniscus
      surgical model of osteoarthritis.
AB  - OBJECTIVE: To detect and determine disease severity of osteoarthritis (OA) using
      a probe activated by matrix metalloproteinase-13 (MMP-13) in vivo in the murine
      destabilised medial meniscus (DMM) surgical model of OA. DESIGN: We have
      previously described MMP12ap and MMP13ap, internally quenched fluorescent peptide
      substrate probes that are activated respectively by MMP-12 and MMP-13. Here we
      used these probes to follow enzyme activity in vivo in mice knees 4, 6 and 8
      weeks following DMM surgery. After in vivo optical imaging, disease severity was
      determined through traditional histological analysis. The amount of probe
      activation was analysed for discrimination between DMM, contralateral and sham
      operated knees, as well as for congruence between activity and histological
      damage. RESULTS: There was no specific activation of MMP12ap at the time points
      observed between sham operated and DMM operated, or their respective
      contralateral joints. The activation of the MMP13ap in the DMM model was highest
      6 weeks after surgery, but was only specific compared against sham surgery 8
      weeks after surgery (1.5-fold increase). The activation of MMP13ap correlated
      with histological damage 6 and 8 weeks after surgery, with correlations of 0.484
      (P = 0.0032) and 0.478 respectively (P = 0.0049). This correlation dropped to
      0.218 (P = 0.011) if all data were considered. CONCLUSION: The current MMP-13
      activity probe is suitable for the discrimination between DMM and sham or
      contralateral knees 8 weeks after surgery, when cartilage loss is typified by the
      appearance of small fissures up to the tidemark, but not earlier. This activity
      correlates with the histological damage observed.

PMID- 24747175
TI  - Sensing core histone phosphorylation - a matter of perfect timing.
AB  - Systematic analysis of histone modifications has revealed a plethora of
      posttranslational modifications that mediate changes in chromatin structure and
      gene expression. Histone phosphorylation is a transient histone modification that
      becomes induced by extracellular signals, DNA damage or entry into mitosis.
      Importantly, phosphorylation of histone proteins does lead not only to the
      binding of specific reader proteins but also to changes in the affinity for
      readers or writers of other histone modifications. This induces a cross-talk
      between different chromatin modifications that allows the spatio-temporal control
      of chromatin-associated events. In this review we will summarize the progress in
      our current knowledge of factors sensing reversible histone phosphorylation in
      different biological scenarios. This article is part of a Special Issue entitled:
      Molecular mechanisms of histone modification function. 

PMID- 24747176
TI  - Transcriptional regulation of the human thromboxane A2 receptor gene by Wilms'
      tumor (WT)1 and hypermethylated in cancer (HIC) 1 in prostate and breast cancers.
AB  - The prostanoid thromboxane (TX) A(2) plays a central role in hemostasis and is
      increasingly implicated in neoplastic disease, including prostate and breast
      cancers. In humans, TXA(2) signals through the TPalpha and TPbeta isoforms of the
      T prostanoid receptor, two structurally related receptors transcriptionally
      regulated by distinct promoters, Prm1 and Prm3, respectively, within the TP gene.
      Focusing on TPalpha, the current study investigated its expression and
      transcriptional regulation through Prm1 in prostate and breast cancers.
      Expression of TPalpha correlated with increasing prostate and breast tissue tumor
      grade while the TXA(2) mimetic U46619 promoted both proliferation and migration
      of the respective prostate (PC3) and breast (MCF-7 and MDA-MD-231) derived
      carcinoma cell lines. Through 5' deletional and genetic reporter analyses,
      several functional upstream repressor regions (URRs) were identified within Prm1
      in PC3, MCF-7 and MDA-MB-231 cells while site-directed mutagenesis identified the
      tumor suppressors Wilms' tumor (WT)1 and hypermethylated in cancer (HIC) 1 as the
      trans-acting factors regulating those repressor regions. Chromatin
      immunoprecipitation (ChIP) studies confirmed that WT1 binds in vivo to multiple
      GC-enriched WT1 cis-elements within the URRs of Prm1 in PC3, MCF-7 and MDA-MB-231
      cells. Furthermore, ChIP analyses established that HIC1 binds in vivo to the
      HIC1((b))cis-element within Prm1 in PC3 and MCF-7 cells but not in the MDA-MB-231
      carcinoma line. Collectively, these data establish that WT1 and HIC1, both tumor
      suppressors implicated in prostate and breast cancers, transcriptionally repress
      TPalpha expression and thereby provide a strong genetic basis for understanding
      the role of TXA2 in the progression of certain human cancers.

PMID- 24747178
TI  - A comprehensive overview of exosomes as drug delivery vehicles - endogenous
      nanocarriers for targeted cancer therapy.
AB  - Exosomes denote a class of secreted nanoparticles defined by size, surface
      protein and lipid composition, and the ability to carry RNA and proteins. They
      are important mediators of intercellular communication and regulators of the
      cellular niche, and their altered characteristics in many diseases, such as
      cancer, suggest them to be important both for diagnostic and therapeutic
      purposes, prompting the idea of using exosomes as drug delivery vehicles,
      especially for gene therapy. This review covers the current status of evidence
      presented in the field of exosome-based drug delivery systems. Components for
      successful exosome-based drug delivery, such as choice of donor cell, therapeutic
      cargo, use of targeting peptide, loading method and administration route are
      highlighted and discussed with a general focus pertaining to the results obtained
      in models of different cancer types. In addition, completed and on-going clinical
      trials are described, evaluating exosome-based therapies for the treatment of
      different cancer types. Due to their endogenous origin, exosome-based drug
      delivery systems may have advantages in the treatment of cancer, but their design
      needs further refinement to justify their usage on the clinical scale. 

PMID- 24747177
TI  - Structural biology-based insights into combinatorial readout and crosstalk among
      epigenetic marks.
AB  - Epigenetic mechanisms control gene regulation by writing, reading and erasing
      specific epigenetic marks. Within the context of multi-disciplinary approaches
      applied to investigate epigenetic regulation in diverse systems, structural
      biology techniques have provided insights at the molecular level of key
      interactions between upstream regulators and downstream effectors. The early
      structural efforts focused on studies at the single domain-single mark level have
      been rapidly extended to research at the multiple domain-multiple mark level,
      thereby providing additional insights into connections within the complicated
      epigenetic regulatory network. This review focuses on recent results from
      structural studies on combinatorial readout and crosstalk among epigenetic marks.
      It starts with an overview of multiple readout of histone marks associated with
      both single and dual histone tails, as well as the potential crosstalk between
      them. Next, this review further expands on the simultaneous readout by epigenetic
      modules of histone and DNA marks, thereby establishing connections between
      histone lysine methylation and DNA methylation at the nucleosomal level. Finally,
      the review discusses the role of pre-existing epigenetic marks in directing the
      writing/erasing of certain epigenetic marks. This article is part of a Special
      Issue entitled: Molecular mechanisms of histone modification function. 

PMID- 24747179
TI  - Transient inactivation of the ventral hippocampus in neonatal rats impairs the
      mesolimbic regulation of prefrontal glutamate release in adulthood.
AB  - Cognitive deficits in schizophrenia (SZ) reflect maturational disruptions within
      a neural system that includes the ventral hippocampus (VH), nucleus accumbens
      (NAc), basal forebrain, and prefrontal cortex (PFC). A better understanding of
      these changes may reveal drug targets for more efficacious cognition enhancers.
      We have utilized an animal model in which the above distributed system is
      altered, during a sensitive period of development, by transiently inactivating
      the VH and its efferent projections. We determined the ability of NAc shell
      activation to evoke prefrontal glutamate release in adult male Wistar rats that
      had received saline (Sal) or tetrodotoxin (TTX) as neonates (PD7) or as
      adolescents (PD32). The nucleus accumbens shell (NAcSh) was activated by NMDA
      infusions (0.05-0.30 MUg/0.5 MUL). Basal and evoked glutamate levels were
      measured amperometrically using a glutamate-sensitive microelectrode. There were
      no differences in basal glutamate levels among the groups tested (overall 1.41 +/
      0.26 uM). However, the dose-related stimulation of prefrontal glutamate levels
      seen in control rats treated with saline on PD7 (4.31 +/- 0.22 MUM after 0.15
      MUg) was markedly attenuated in rats treated with TTX on PD7 (0.45 +/- 0.12 MUM
      after 0.15 MUg). This effect was age-dependent as infusions of TTX on PD32 did
      not alter the NMDA-induced increases in glutamate release (4.10 +/- 0.37 MUM
      after 0.15 MUg). Collectively, these findings reveal that transient inactivation
      of VH transmission, during a sensitive period of development, leads to a
      functional mesolimbic-cortical disconnection that produces neurochemical and
      ultimately cognitive impairments resembling those seen in SZ. 

PMID- 24747180
TI  - Impact of in vivo chronic blockade of adenosine A2A receptors on the BDNF
      mediated facilitation of LTP.
AB  - Brain-derived neurotrophic factor (BDNF) through the activation of its receptor
      (TrkB-FL) exert well-described neuroprotective effects playing a major role in
      hippocampal synaptic transmission and plasticity such as long-term potentiation
      (LTP), a molecular surrogate for learning and memory. Impairments in BDNF
      signalling have been associated to several neurodegenerative disorders such as
      Alzheimer's disease (AD). Therefore, the reestablishment of BDNF actions is
      considered a promising strategy for AD treatment. While, most of BDNF synaptic
      actions, namely on LTP, require the activation of adenosine A2A receptor (A2AR),
      the antagonists of A2AR have been proven to prevent AD induced deficits in
      different animal models. Therefore in this work we aimed to evaluate the impact
      of a chronic in vivo oral administration of an A2AR antagonist (KW-6002) in the
      BDNF actions upon hippocampal CA1 LTP. The results showed that chronic blockade
      of A2AR in male Wistar rats inhibits the facilitatory action of BDNF upon LTP on
      hippocampal CA1 area and decreases both mRNA and protein levels of the TrkB-FL
      receptor in hippocampus. These findings imply that BDNF signalling may be
      affected in chronic A2AR blocking conditions. 

PMID- 24747181
TI  - Geniposide and its iridoid analogs exhibit antinociception by acting at the
      spinal GLP-1 receptors.
AB  - We recently discovered that the activation of the spinal glucagon-like peptide-1
      receptors (GLP-1Rs) by the peptidic agonist exenatide produced antinociception in
      chronic pain. We suggested that the spinal GLP-1Rs are a potential target
      molecule for the management of chronic pain. This study evaluated the
      antinociceptive activities of geniposide, a presumed small molecule GLP-1R
      agonist. Geniposide produced concentration-dependent, complete protection against
      hydrogen peroxide-induced oxidative damage in PC12 and HEK293 cells expressing
      rat and human GLP-1Rs, but not in HEK293T cells that do not express GLP-1Rs. The
      orthosteric GLP-1R antagonist exendin(9-39) right-shifted the concentration
      response curve of geniposide without changing the maximal protection, with
      identical pA2 values in both cell lines. Subcutaneous and oral geniposide dose
      dependently blocked the formalin-induced tonic response but not the acute
      flinching response. Subcutaneous and oral geniposide had maximum inhibition of
      72% and 68%, and ED50s of 13.1 and 52.7 mg/kg, respectively. Seven days of
      multidaily subcutaneous geniposide and exenatide injections did not induce
      antinociceptive tolerance. Intrathecal geniposide induced dose-dependent
      antinociception, which was completely prevented by spinal exendin(9-39),
      siRNA/GLP-1R and cyclic AMP/PKA pathway inhibitors. The geniposide iridoid
      analogs geniposidic acid, genipin methyl ether, 1,10-anhydrogenipin, loganin and
      catalpol effectively inhibited hydrogen peroxide-induced oxidative damage and
      formalin pain in an exendin(9-39)-reversible manner. Our results suggest that
      geniposide and its iridoid analogs produce antinociception during persistent pain
      by activating the spinal GLP-1Rs and that the iridoids represented by geniposide
      are orthosteric agonists of GLP-1Rs that function similarly in humans and rats
      and presumably act at the same binding site as exendin(9-39). 

PMID- 24747183
TI  - LoCIM-tool: An expert's assistant for inferring the major contributor's alleles
      in mixed consensus DNA profiles.
AB  - When dealing with mixed DNA profiles where contributors have donated DNA in
      unequal amounts, it is often useful to deduce the genotype of the major
      contributor. Inference of a major contributor's genotype empowers storage of the
      DNA profile in a DNA database (DDB), which is especially of interest in cases
      without a suspect. When a major contributor's genotype cannot be inferred
      straightforwardly, for instance because low level components are present,
      replicate analyses can be prepared and combined into a consensus profile. Here we
      describe an automated and freely available tool to deduce the major component's
      alleles in mixed consensus DNA profiles. In these consensus profiles, theoretical
      peak heights (PHs) are assigned to the alleles using the sum of the PHs in the
      individual amplifications. The LoCIM-tool (Locus Classification & Inference of
      the Major-tool) uses these PHs plus parameters on the stochastic threshold,
      heterozygote balance (HB) and major to minor(s) ratio to classify every locus as
      a type 1, type 2 or type 3 locus, which represent classes of increasing
      complexity. Based on the type of locus, the LoCIM-tool applies an inclusion
      percentage to deduce the alleles for the major contributor. Using the LoCIM-tool,
      99.9% of all type 1 loci and 96.7% of all type 2 loci were inferred correctly
      from a large set of consensus DNA profiles that were generated from mixtures
      varying for the mixture ratio, amount of DNA per contributor, number of
      contributors, quality of DNA, and allele sharing among the contributors. For type
      3 loci, we aimed at inferring the major contributor's alleles and possibly extra
      alleles, which occurred for 87.2% of all type 3 loci analysed using the LoCIM
      tool. When compared to the overall results of manual inference by a group of
      forensic scientists, the LoCIM-tool obtains a higher percentage of correctly
      inferred loci. From our results, we conclude that the LoCIM-tool presents an
      objective, uniform and fast method to reliably deduce alleles of a major
      component.

PMID- 24747182
TI  - Contrasting changes in extracellular dopamine and glutamate along the
      rostrocaudal axis of the anterior cingulate cortex of the rat following an acute
      d-amphetamine or dopamine challenge.
AB  - There is evidence for functional specificity of subregions along the rostrocaudal
      axis of the anterior cingulate cortex (ACC). The subregion-specific distribution
      of dopaminergic afferents and glutamatergic efferents along the ACC make these
      obvious candidates for coding such regional responses. We investigated this
      possibility using microdialysis in freely-moving rats to compare changes in
      extracellular dopamine and glutamate in the rostral ('rACC': Cg1 and Cg3
      (prelimbic area)) and caudal ('cACC': Cg1 and Cg2) ACC induced by systemic or
      local administration of d-amphetamine. Systemic administration of d-amphetamine
      (3 mg/kg, i.p.) caused a transient increase in extracellular dopamine in the
      rACC, but an apparent increase in the cACC of the same animals was less clearly
      defined. Local infusion of d-amphetamine increased dopamine efflux in the rACC,
      only. Glutamate efflux in the rACC was increased by local infusion of dopamine (5
      50 MUM), which had negligible effect in the cACC, but only systemic
      administration of d-amphetamine increased glutamate efflux and only in the cACC.
      The asymmetry in the neurochemical responses within the rACC and cACC, to the
      same experimental challenges, could help explain why different subregions are
      recruited in the response to specific environmental and somatosensory stimuli and
      should be taken into account when studying the regulation of neurotransmission in
      the ACC. This article is part of the Special Issue entitled 'CNS Stimulants'.

PMID- 24747184
TI  - Development of a SNP set for human identification: A set with high powers of
      discrimination which yields high genetic information from naturally degraded DNA
      samples in the Thai population.
AB  - This study describes the development of a SNP typing system for human
      identification in the Thai population, in particular for extremely degraded DNA
      samples. A highly informative SNP marker set for forensic identification was
      identified, and a multiplex PCR-based Invader assay was developed. Fifty-one
      highly informative autosomal SNP markers and three sex determination SNP markers
      were amplified in two multiplex PCR reactions and then detected using Invader
      assay reactions. The average PCR product size was 71 base pairs. The match
      probability of the 54-SNP marker set in 124 Thai individuals was 1.48*10(-21),
      higher than that of STR typing, suggesting that this 54-SNP marker set is
      beneficial for forensic identification in the Thai population. The selected SNP
      marker set was also evaluated in 90 artificially degraded samples, and in 128
      naturally degraded DNA samples from real forensic casework which had shown no
      profiles or incomplete profiles when examined using a commercial STR typing
      system. A total of 56 degraded samples (44%) achieved the matching probability
      (PM) equivalent to STR gold standard analysis (successful genotyping of 44 SNP
      markers) for human identification. These data indicated that our novel 54-SNP
      marker set provides a very useful and valuable approach for forensic
      identification in the Thai population, especially in the case of highly to
      extremely degraded DNA. In summary, we have developed a set of 54 Thai-specific
      SNPs for human identification which have higher discrimination power than STR
      genotyping. The PCRs for these 54 SNP markers were successfully combined into two
      multiplex reactions and detected with an Invader assay. This novel SNP genotyping
      system also yields high levels of genetic information from naturally degraded
      samples, even though there are much more difficult to recover than artificially
      degraded samples. 

PMID- 24747187
TI  - Synthesis, characterization, theoretical, anti-bacterial and molecular docking
      studies of quinoline based chalcones as a DNA gyrase inhibitor.
AB  - A series of fourteen (A1-A14) new qunioline based chalcones were synthesized by
      condensing 2,7-dichloro-8-methyl-3-formyl quinoline with acetophenone and
      acetylthiophenes, and subsequently characterized by IR, NMR and Mass
      spectroscopy. All the compounds were screened for antibacterial activities and
      found potentially active antibacterial agents. Bioassay, theoretical and dockings
      studies with DNA gyrase (the enzyme required for super coiling of DNA of
      bacteria) results showed that the type and positions of the substituents seemed
      to be critical for their antibacterial activities. The bromo and chloro
      substituted chalcone displayed high anti-bacterial activity. The A4 and A6 showed
      high interaction with DNA gyrase, contributing high free binding energy (DeltaG 
      8.18 and -8.88 kcal).

PMID- 24747185
TI  - Transport proteins promoting Escherichia coli pathogenesis.
AB  - Escherichia coli is a genetically diverse species infecting hundreds of millions
      of people worldwide annually. We examined seven well-characterized E. coli
      pathogens causing urinary tract infections, gastroenteritis, pyelonephritis and
      haemorrhagic colitis. Their transport proteins were identified and compared with
      each other and a non-pathogenic E. coli K12 strain to identify transport proteins
      related to pathogenesis. Each pathogen possesses a unique set of protein
      secretion systems for export to the cell surface or for injecting effector
      proteins into host cells. Pathogens have increased numbers of iron siderophore
      receptors and ABC iron uptake transporters, but the numbers and types of low
      affinity secondary iron carriers were uniform in all strains. The presence of
      outer membrane iron complex receptors and high-affinity ABC iron uptake systems
      correlated, suggesting co-evolution. Each pathovar encodes a different set of
      pore-forming toxins and virulence-related outer membrane proteins lacking in K12.
      Intracellular pathogens proved to have a characteristically distinctive set of
      nutrient uptake porters, different from those of extracellular pathogens. The
      results presented in this report provide information about transport systems
      relevant to various types of E. coli pathogenesis that can be exploited in future
      basic and applied studies. 

PMID- 24747188
TI  - Synthesis and evaluation of novel isoxazolyl chalcones as potential anticancer
      agents.
AB  - A series of novel isoxazolyl chalcones were synthesized and evaluated for their
      activities in vitro against four types of human non-small cell lung cancer cells,
      including H1792, H157, A549 and Calu-1 cells. The preliminary biological
      screening showed that compounds 5d and 5f-i exhibited significant cytotoxicity,
      particularly, compounds 5f and 5h were identified as the most potent anticancer
      agents with IC50 values 1.35-2.07 MUM and 7.27-11.07 MUM against H175, A549 and
      Calu-1 cell lines, respectively. Compounds 5f-i could induce apoptosis in A549
      cells by death receptor 5 (DR5) mediated extrinsicpathways. The preliminary
      structure-activity relationship study showed that compounds bearing electron
      withdrawing groups (EWG) at the 2-position of the phenyl ring in Ar group were
      more effective than those with EWG at 4-position. These results further
      demonstrated that the scaffolds designed in this work might lead to the discovery
      of novel anti-lung cancer agents.

PMID- 24747189
TI  - Mining the 3'UTR of autism-implicated genes for SNPs perturbing microRNA
      regulation.
AB  - Autism spectrum disorder (ASD) refers to a group of childhood neurodevelopmental
      disorders with polygenic etiology. The expression of many genes implicated in ASD
      is tightly regulated by various factors including microRNAs (miRNAs), a class of
      noncoding RNAs ~22 nucleotides in length that function to suppress translation by
      pairing with 'miRNA recognition elements' (MREs) present in the 3'untranslated
      region (3'UTR) of target mRNAs. This emphasizes the role played by miRNAs in
      regulating neurogenesis, brain development and differentiation and hence any
      perturbations in this regulatory mechanism might affect these processes as well.
      Recently, single nucleotide polymorphisms (SNPs) present within 3'UTRs of mRNAs
      have been shown to modulate existing MREs or even create new MREs. Therefore, we
      hypothesized that SNPs perturbing miRNA-mediated gene regulation might lead to
      aberrant expression of autism-implicated genes, thus resulting in disease
      predisposition or pathogenesis in at least a subpopulation of ASD individuals. We
      developed a systematic computational pipeline that integrates data from well
      established databases. By following a stringent selection criterion, we
      identified 9 MRE-modulating SNPs and another 12 MRE-creating SNPs in the 3'UTR of
      autism-implicated genes. These high-confidence candidate SNPs may play roles in
      ASD and hence would be valuable for further functional validation.

PMID- 24747190
TI  - PrimerSeq: Design and visualization of RT-PCR primers for alternative splicing
      using RNA-seq data.
AB  - The vast majority of multi-exon genes in higher eukaryotes are alternatively
      spliced and changes in alternative splicing (AS) can impact gene function or
      cause disease. High-throughput RNA sequencing (RNA-seq) has become a powerful
      technology for transcriptome-wide analysis of AS, but RT-PCR still remains the
      gold-standard approach for quantifying and validating exon splicing levels. We
      have developed PrimerSeq, a user-friendly software for systematic design and
      visualization of RT-PCR primers using RNA-seq data. PrimerSeq incorporates user
      provided transcriptome profiles (i.e., RNA-seq data) in the design process, and
      is particularly useful for large-scale quantitative analysis of AS events
      discovered from RNA-seq experiments. PrimerSeq features a graphical user
      interface (GUI) that displays the RNA-seq data juxtaposed with the expected RT
      PCR results. To enable primer design and visualization on user-provided RNA-seq
      data and transcript annotations, we have developed PrimerSeq as a stand-alone
      software that runs on local computers. PrimerSeq is freely available for Windows
      and Mac OS X along with source code at http://primerseq.sourceforge.net/. With
      the growing popularity of RNA-seq for transcriptome studies, we expect PrimerSeq
      to help bridge the gap between high-throughput RNA-seq discovery of AS events and
      molecular analysis of candidate events by RT-PCR.

PMID- 24747191
TI  - Genome-wide mapping of cellular protein-RNA interactions enabled by chemical
      crosslinking.
AB  - RNA-protein interactions influence many biological processes. Identifying the
      binding sites of RNA-binding proteins (RBPs) remains one of the most fundamental
      and important challenges to the studies of such interactions. Capturing RNA and
      RBPs via chemical crosslinking allows stringent purification procedures that
      significantly remove the non-specific RNA and protein interactions. Two major
      types of chemical crosslinking strategies have been developed to date, i.e., UV
      enabled crosslinking and enzymatic mechanism-based covalent capture. In this
      review, we compare such strategies and their current applications, with an
      emphasis on the technologies themselves rather than the biology that has been
      revealed. We hope such methods could benefit broader audience and also urge for
      the development of new methods to study RNA-RBP interactions.

PMID- 24747192
TI  - The long term impact of cataract surgery on quality of life, activities and
      poverty: results from a six year longitudinal study in Bangladesh and the
      Philippines.
AB  - BACKGROUND: Cataract surgery has been shown to improve quality of life and
      household economy in the short term. However, it is unclear whether these
      benefits are sustained over time. This study aims to assess the six year impact
      of cataract surgery on health related quality of life (HRQoL), daily activities
      and economic poverty in Bangladesh and The Philippines. METHODS AND FINDINGS:
      This was a longitudinal study. At baseline people aged >=50 years with visual
      impairment due to cataract ('cases') and age-, sex-matched controls without
      visual impairment were interviewed about vision specific and generic HRQoL, daily
      activities and economic indicators (household per capita expenditure, assets and
      self-rated wealth). Cases were offered free or subsidised cataract surgery. Cases
      and controls were re-interviewed approximately one and six years later. At
      baseline across the two countries there were 455 cases and 443 controls. Fifty
      percent of cases attended for surgery. Response rates at six years were 47% for
      operated cases and 53% for controls. At baseline cases had poorer health and
      vision related QoL, were less likely to undertake productive activities, more
      likely to receive assistance with activities and were poorer compared to controls
      (p<0.05). One year after surgery there were significant increases in HRQoL,
      participation and time spent in productive activities and per capita expenditure
      and reduction in assistance with activities so that the operated cases were
      similar to controls. These increases were still evident after six years with the
      exception that time spent on productive activities decreased among both cases and
      controls. CONCLUSION: Cataract causing visual loss is associated with reduced
      HRQoL and economic poverty among older adults in low-income countries. Cataract
      surgery improves the HRQoL of the individual and economy of the household. The
      findings of this study suggest these benefits are sustained in the long term.

PMID- 24747193
TI  - Monoarthritis-induced emotional and cognitive impairments in rats are sensitive
      to low systemic doses or intra-amygdala injections of morphine.
AB  - Chronic pain is a multidimensional experience that not only includes changes in
      nociception but also impairments in emotional and cognitive functions, not often
      taken into account in preclinical research. The present study investigated
      emotional and cognitive impairments in an animal model of persistent inflammatory
      pain as well as the involvement of the basolateral complex (BLC) of the amygdala
      in these components. Monoarthritis was induced by intra-articular injection of
      complete Freund's adjuvant. Mechanical hypersensitivity, anxiety and depressive
      like behaviours as well as cognitive capacities were assessed using several
      tests, such as von Frey, social interaction, open field, saccharin preference,
      spatial and social recognition memory tests. The effects of morphine administered
      systemically or into the BLC of the amygdala were also studied. Monoarthritic
      rats exhibited mechanical hypersensitivity, anxiety and depressive-like
      behaviours as well as cognitive impairments. Whereas low systemic doses and intra
      BLC infusion of morphine failed to reduce mechanical hypersensitivity, they
      reversed monoarthritis-induced anxiety-like behaviours and cognitive impairments.
      Our findings further support a crucial role of amygdala in the effect of morphine
      on emotional/cognitive components of pain and not on mechanical hypersensitivity.
      Finally, our study highlights the interest of a multi-behavioural approach in the
      assessment of pain and the analgesic effect of drugs. 

PMID- 24747194
TI  - Assaying proteasomal degradation in a cell-free system in plants.
AB  - The ubiquitin-proteasome pathway for protein degradation has emerged as one of
      the most important mechanisms for regulation of a wide spectrum of cellular
      functions in virtually all eukaryotic organisms. Specifically, in plants, the
      ubiquitin/26S proteasome system (UPS) regulates protein degradation and
      contributes significantly to development of a wide range of processes, including
      immune response, development and programmed cell death. Moreover, increasing
      evidence suggests that numerous plant pathogens, such as Agrobacterium, exploit
      the host UPS for efficient infection, emphasizing the importance of UPS in plant
      pathogen interactions. The substrate specificity of UPS is achieved by the E3
      ubiquitin ligase that acts in concert with the E1 and E2 ligases to recognize and
      mark specific protein molecules destined for degradation by attaching to them
      chains of ubiquitin molecules. One class of the E3 ligases is the SCF
      (Skp1/Cullin/F-box protein) complex, which specifically recognizes the UPS
      substrates and targets them for ubiquitination via its F-box protein component.
      To investigate a potential role of UPS in a biological process of interest, it is
      important to devise a simple and reliable assay for UPS-mediated protein
      degradation. Here, we describe one such assay using a plant cell-free system.
      This assay can be adapted for studies of the roles of regulated protein
      degradation in diverse cellular processes, with a special focus on the F-box
      protein-substrate interactions. 

PMID- 24747195
TI  - Spatial variability in HIV prevalence declines in several countries in sub
      Saharan Africa.
AB  - Evidence suggests substantial declines in HIV prevalence in parts of sub-Saharan
      Africa. However, the observed aggregate declines at the national level may
      obscure local variations in the temporal dynamics of the infection. Using spatial
      scan statistics, we identified marked spatial variability in the within-country
      declines in HIV prevalence in Tanzania, Malawi, Kenya, and Zimbabwe. Our study
      suggests that the declines in the national HIV prevalence in some of the SSA
      countries may not be representative of downward trends in prevalence in areas of
      high HIV prevalence, as much as the result of sharp declines in prevalence in
      areas of already low HIV prevalence. Our findings provide insights for resource
      allocation and HIV prevention interventions in these countries. 

PMID- 24747196
TI  - The ChroP approach combines ChIP and mass spectrometry to dissect locus-specific
      proteomic landscapes of chromatin.
AB  - Chromatin is a highly dynamic nucleoprotein complex made of DNA and proteins that
      controls various DNA-dependent processes. Chromatin structure and function at
      specific regions is regulated by the local enrichment of histone post
      translational modifications (hPTMs) and variants, chromatin-binding proteins,
      including transcription factors, and DNA methylation. The proteomic
      characterization of chromatin composition at distinct functional regions has been
      so far hampered by the lack of efficient protocols to enrich such domains at the
      appropriate purity and amount for the subsequent in-depth analysis by Mass
      Spectrometry (MS). We describe here a newly designed chromatin proteomics
      strategy, named ChroP (Chromatin Proteomics), whereby a preparative chromatin
      immunoprecipitation is used to isolate distinct chromatin regions whose features,
      in terms of hPTMs, variants and co-associated non-histonic proteins, are analyzed
      by MS. We illustrate here the setting up of ChroP for the enrichment and analysis
      of transcriptionally silent heterochromatic regions, marked by the presence of
      tri-methylation of lysine 9 on histone H3. The results achieved demonstrate the
      potential of ChroP in thoroughly characterizing the heterochromatin proteome and
      prove it as a powerful analytical strategy for understanding how the distinct
      protein determinants of chromatin interact and synergize to establish locus
      specific structural and functional configurations. 

PMID- 24747197
TI  - Association of mechanical ventilation and flue use in heaters with asthma
      symptoms in Japanese schoolchildren: a cross-sectional study in Sapporo, Japan.
AB  - BACKGROUND: Use of fuel heaters is associated with childhood asthma. However, no
      studies have evaluated the associations of flue use and mechanical ventilation
      (ventilation) with asthma symptoms in schoolchildren. METHODS: This cross
      sectional study investigated schoolchildren in grades 1 through 6 (age 6-12
      years) in Sapporo, Japan. From November 2008 through January 2009, parents
      completed questionnaires regarding their home environment and their children's
      asthma symptoms. RESULTS: In total, 4445 (69.5%) parents of 6393 children
      returned the questionnaire. After excluding incomplete responses, data on 3874
      children (60.6%) were analyzed. The prevalence of current asthma symptoms and
      ever asthma symptoms were 12.8% and 30.9%, respectively. As compared with
      electric heaters, current asthma symptoms was associated with use of flued
      heaters without ventilation (OR = 1.62; 95% CI, 1.03-2.64) and unflued heaters
      with ventilation (OR = 1.77; 95% CI, 1.09-2.95) or without ventilation (OR =
      2.23; 95% CI, 1.31-3.85). Regardless of dampness, unflued heaters were
      significantly associated with current asthma symptoms in the presence and absence
      of ventilation. CONCLUSIONS: Use of unflued heaters was associated with current
      asthma symptoms, regardless of dampness. In particular, the prevalence of current
      asthma symptoms was higher in the absence of ventilation than in the presence of
      ventilation. Ever asthma symptoms was only associated with use of unflued heaters
      without ventilation. Consequently, use of fuel heaters, especially those that
      have no flue or ventilation, deserves attention, as their use might be associated
      with childhood asthma symptoms.

PMID- 24747198
TI  - Validation of methods to control for immortal time bias in a
      pharmacoepidemiologic analysis of renin-angiotensin system inhibitors in type 2
      diabetes.
AB  - BACKGROUND: Pharmacoepidemiologic analysis can confirm whether drug efficacy in a
      randomized controlled trial (RCT) translates to effectiveness in real settings.
      We examined methods used to control for immortal time bias in an analysis of
      renin-angiotensin system (RAS) inhibitors as the reference cardioprotective drug.
      METHODS: We analyzed data from 3928 patients with type 2 diabetes who were
      recruited into the Hong Kong Diabetes Registry between 1996 and 2005 and followed
      up to July 30, 2005. Different Cox models were used to obtain hazard ratios (HRs)
      for cardiovascular disease (CVD) associated with RAS inhibitors. These HRs were
      then compared to the HR of 0.92 reported in a recent meta-analysis of RCTs.
      RESULTS: During a median follow-up period of 5.45 years, 7.23% (n = 284) patients
      developed CVD and 38.7% (n = 1519) were started on RAS inhibitors, with 39.1% of
      immortal time among the users. In multivariable analysis, time-dependent drug
      exposure Cox models and Cox models that moved immortal time from users to
      nonusers both severely inflated the HR, and time-fixed models that included
      immortal time deflated the HR. Use of time-fixed Cox models that excluded
      immortal time resulted in a HR of only 0.89 (95% CI, 0.68-1.17) for CVD
      associated with RAS inhibitors, which is closer to the values reported in RCTs.
      CONCLUSIONS: In pharmacoepidemiologic analysis, time-dependent drug exposure
      models and models that move immortal time from users to nonusers may introduce
      substantial bias in investigations of the effects of RAS inhibitors on CVD in
      type 2 diabetes.

PMID- 24747199
TI  - Effects of various squalene epoxides on coenzyme Q and cholesterol synthesis.
AB  - 2,3-Oxidosqualene is an intermediate in cholesterol biosynthesis and 2,3:22,23
      dioxidosqualene act as the substrate for an alternative pathway that produces
      24(S),25-epoxycholesterol which effects cholesterol homeostasis. In light of our
      previous findings concerning the biological effects of certain epoxidated all
      trans-polyisoprenes, the effects of squalene carrying epoxy moieties on the
      second and third isoprene residues were investigated here. In cultures of HepG2
      cells both monoepoxides of squalene and one of their hydrolytic products
      inhibited cholesterol synthesis and stimulated the synthesis of coenzyme Q (CoQ).
      Upon prolonged treatment the cholesterol content of these cells and its labeling
      with [(3)H]mevalonate were reduced, while the amount and labeling of CoQ
      increased. Injection of the squalene monoepoxides into mice once daily for 6days
      elevated the level of CoQ in their blood, but did not change the cholesterol
      level. The same effects were observed upon treatment of apoE-deficient mice and
      diabetic GK-rats. This treatment increased the hepatic level of CoQ10 in mice,
      but the amount of CoQ9, which is the major form, was unaffected. The presence of
      the active compounds in the blood was supported by the finding that cholesterol
      synthesis in the white blood cells was inhibited. Since the ratio of CoQ9/CoQ10
      varies depending on the experimental conditions, the cells were titrated with
      substrate and inhibitors, leading to the conclusion that the intracellular
      isopentenyl-PP pool is a regulator of this ratio. Our present findings indicate
      that oxidosqualenes may be useful for stimulating both the synthesis and level of
      CoQ both in vitro and in vivo. 

PMID- 24747200
TI  - SIBLING family genes and bone mineral density: association and allele-specific
      expression in humans.
AB  - Osteoporosis is a common complex disorder with reduced bone mineral density (BMD)
      and increased susceptibility to fracture. Peak BMD is one of the primary
      determinants of osteoporotic fracture risk, and is under substantial genetic
      control. Extracellular matrix, a major component of the bone, influences BMD by
      regulating mineral deposition and maintaining cellular activity. It contains
      several SIBLING family proteins, null mutations of which cause mineralization
      defects in humans. In this study, we tested 59 single-nucleotide polymorphisms
      (SNPs) located in the 5 SIBLING family genes (DSPP, DMP1, IBSP, MEPE and SPP1)
      for association with normal variation in peak BMD in healthy men and women. We
      measured femoral neck (FN) and lumbar spine (LS) areal BMD by dual energy x-ray
      absorptiometry (DXA) in 1692 premenopausal European-American women, 512
      premenopausal African-American women and 715 European-American men. SNPs were
      tested for association with FN and LS-BMD in the 3 subsamples. In the European
      American women, we observed association (p<=0.005) with LS-BMD for SNPs in DSPP,
      IBSP and MEPE, and for FN-BMD with SNPs in DMP1 and IBSP. Allele-specific
      regulation of gene expression (ASE) is an important mechanism in which an allele
      giving rise to modest influence in transcript abundance might result in a
      predisposition to disease. To identify whether there was ASE of SIBLING family
      genes at these SNPs, we examined 52 human bone samples obtained from the femoral
      neck during surgical hip replacement (27 female, 25 male; 44 European-American
      and 8 African-American). We observed unidirectional ASE for the IBSP gene, with
      lower expression of the G allele compared to the A allele for SNP rs17013181. Our
      data suggest that SNPs within the SIBLING genes may contribute to normal
      variation of peak BMD. Further studies are necessary to identify the functional
      variants and to determine the mechanisms underlying the differences in ASE and
      how these differences relate to the pathophysiology of osteoporosis. 

PMID- 24747201
TI  - Can medications be safely withdrawn in patients with stable chronic heart
      failure? systematic review and meta-analysis.
AB  - BACKGROUND: Heart failure (HF) therapy involves use of multiple medications.
      There is little guidance on the safety and impact on clinical outcomes of
      stopping HF medications. METHODS AND RESULTS: A comprehensive systematic search
      for studies of drug therapy withdrawal in HF was performed. Meta-analysis of the
      risk ratio (RR) was performed with the use of the Mantel-Haenszel random effects
      model for all-cause mortality and cardiovascular outcomes. Twenty-six studies met
      the inclusion criteria. Studies on withdrawal of renin-angiotensin-aldosterone
      system (RAAS) inhibitors and beta-blockers in HF are scarce and small, yet show
      relatively convincingly that such withdrawals have untoward effects on cardiac
      structure, symptoms, and major outcomes. Meta-analysis of 7 studies of digoxin
      withdrawal (2,987 participants) without background beta-blocker showed increased
      HF hospitalizations (RR 1.30, 95% confidence interval [CI] 1.16-1.46; P < .0001),
      but no impact on all-cause mortality (RR 1.00, 95% CI 0.90-1.12; P = .06) nor
      reduction in all-cause hospitalization (RR 1.03, 95% CI 0.98-1.09; P = .27).
      Diuretic withdrawal trials demonstrated an ongoing need for these agents in
      chronic HF. Studies in peripartum cardiomyopathy showed that medications could be
      successfully withdrawn after recovery. CONCLUSION: Current evidence discourages
      any attempt to discontinue RAAS inhibitors or beta-blockers in patients with
      stable HF, regardless of clinical and/or echocardiographic status. Formal
      withdrawal trials of other classes are needed.

PMID- 24747202
TI  - Impedimetric DNA-biosensor for the study of anti-cancer action of mitomycin C:
      comparison between acid and electroreductive activation.
AB  - An electrochemical protocol is described for direct monitoring of anti-cancer
      properties of MMC. Using electrochemical impedance spectroscopy, a pretreated
      pencil graphite electrode (PGE) modified with multiwall carbon nanotubes (MWCNTs)
      and poly(diallyldimethylmmonium chloride), PDDA, decorated with ds-DNA was
      employed in this study to identify DNA damages induced by MMC. The change in
      charge transfer resistance after incubation of the DNA-biosensor in MMC solution
      for a known time was used as indication of DNA damage. It was found that MMC did
      not interact with DNA. As MMC does not inherently possess any anti-cancer
      activity, it is, therefore, necessary to activate it by either of two ways:
      activation in acidic media or electrochemical activation. Incubation of DNA
      modified electrode in activated MMC led to alterations in DNA and changes in its
      electrochemical properties (which forms the theme of the present study). Acid and
      electroreductive MMC activations were compared and different adducts were
      subsequently generated, suggesting that the drug can bind to DNA in more than one
      way. Impedance spectroscopy was used for the first time as a novel technique for
      detecting DNA-drug adducts. 

PMID- 24747203
TI  - A fluorometric biosensor based on H2O2-sensitive nanoclusters for the detection
      of acetylcholine.
AB  - We have constructed a simple, cost-effective, label-free, selective and sensitive
      biosensor based on the fluorescence quenching of protein-stabilized nanoclusters
      (NCs) for the detection of acetylcholine (ACh). In this assay,
      acetylcholineaterase (AChE) catalyzes the hydrolysis of ACh to form choline,
      which in turn is oxidized by choline oxidase (ChOx) to generate H2O2 which
      induces the fluorescence quenching of NCs. By virtue of this specific response,
      the detection limit of a fluorescent biosensor for determination of ACh was 5 pM
      (signal/noise=3), and the linear range was 0.1-20 nM. In addition, we use the
      proposed method to detect ACh in human blood, in which the concentration of ACh
      is ca. 6.83 nM, and the recoveries of the spiked sample range from 93% to 102%.
      The result agree with a commercial assay kit, suggesting that the excellent
      biosensor can be used in the practice detection of ACh.

PMID- 24747204
TI  - Highly sensitive and selective glucose sensor based on ultraviolet-treated
      nematic liquid crystals.
AB  - Glucose is an extremely important biomolecule, and the ability to sense it has
      played a significant role in facilitating the understanding of many biological
      processes. Here, we report a novel glucose sensor based on ultraviolet (UV)
      treated nematic liquid crystals. Submerging UV-treated 4-cyano-4'-pentylbiphenyl
      (5CB) in a glucose solution (while carefully adjusting its pH to 7.5 with NaOH
      and HCl) triggered an optical response, from dark to bright, observed with a
      polarized microscope. Notably, 5CB was located inside a glucose oxidase (GOx)
      modified gold grid. We exploited this pH-driven phenomenon to design a new
      glucose sensor. This device could detect as little as 1 pM analyte, which is 3
      orders of magnitude lower than the detection limit of the most sensitive glucose
      sensor currently available. It also exhibits high selectivity due to GOx
      modification. Thus, this is a promising technique for glucose detection, not only
      for clinical diagnostics, but also for sensing low levels of glucose in a
      biological environment (e.g., single cells and bacterial cultures).

PMID- 24747205
TI  - Phosphorescent quantum dots/doxorubicin nanohybrids based on photoinduced
      electron transfer for detection of DNA.
AB  - MPA-capped Mn-doped ZnS QDs/DXR nanohybrids (MPA: 3-mercaptopropionic acid; QDs:
      quantum dots; DXR: cetyltrimethyl ammonium bromide) were constructed via
      photoinduced electron transfer (PIET) and then used as a room-temperature
      phosphorescence (RTP) probe for detection of DNA. DXR as a quencher will quench
      the RTP of Mn-doped ZnS QDs via PIET, thereby forming Mn-doped ZnS QDs/DXR
      nanohybrids and storing RTP. With the addition of DNA, it will be inserted into
      DXR and thus DXR will be competitively desorbed from the surface of Mn-doped ZnS
      QDs, thereby releasing the RTP of Mn-doped ZnS QDs. Based on this, a new method
      for DNA detection was built. The sensor for DNA has a detection limit of 0.039 mg
      L(-1) and a linear range from 0.1 to 14 mg L(-1). The present QDs-based RTP
      method does not need deoxidants or other inducers as required by conventional RTP
      detection methods, and avoids interference from autofluorescence and the
      scattering light of the matrix that are encountered in spectrofluorometry.
      Therefore, this method can be used to detect the DNA content in body fluid.

PMID- 24747206
TI  - Graphene functionalized porous Au-paper based electrochemiluminescence device for
      detection of DNA using luminescent silver nanoparticles coated calcium
      carbonate/carboxymethyl chitosan hybrid microspheres as labels.
AB  - In the paper, a simple and sensitive electrochemiluminescence (ECL) DNA sensor
      based on graphene-modified porous Au-paper working electrode (GR/Au-PWE) and
      calcium carbonate/carboxymethyl chitosan (CaCO3/CMC) hybrid microspheres @
      luminescent silver nanoparticles (AgNPs) composites was developed. The GR/Au-PWE
      with excellent conductivity was successfully prepared for the immobilization of
      capture probe. The CaCO3/CMC hybrid microspheres were prepared by the
      precipitation of calcium carbonate in an aqueous solution containing CMC. The
      AgNPs was synthesized by thermal reduction of silver ions in glycine matrix,
      taking advantage of the solid-state matrix to control the nucleation and
      migration of reduced silver atoms. The CaCO3/CMC@AgNPs composites exhibited 3.6
      times higher ECL intensity than the pure AgNPs-labeled reporter DNA. Taking
      advantage of dual-amplification effects, the paper-based DNA sensor could detect
      the target DNA quantitatively, in the range of 4.0*10(-17)-5.0*10(-11) M, with a
      limit of detection as low as 8.5*10(-18) M, and perform excellent selectivity.
      The simple, low-cost, sensitive device could be easily applied for point-of-care
      testing, public health and environmental monitoring in remote regions, developing
      or developed countries.

PMID- 24747207
TI  - Loss of p16(INK4a) is associated with reduced patient survival in soft tissue
      tumours, and indicates a senescence barrier.
AB  - AIMS: p16(INK4a) is an important factor in carcinogenesis, and its expression is
      linked to oncogene-induced senescence. Very recently it was shown that
      upregulation and downregulation of p16 indicates a senescence barrier in the
      serrated route of colorectal cancer. However, in soft tissue sarcoma (STS), the
      senescence mechanism is still not understood. In this study, we analysed a well
      characterised cohort of STS for p16(INK4a) expression and correlated the results
      with clinicopathological parameters including survival. METHODS: Tissue
      microarrays (TMA) of 183 soft tissue and bone tumours were analysed
      immunohistochemically. Furthermore, mRNA expression of p16(INK4a) was evaluated
      in four sarcoma cell lines, and a demethylation test was performed by treatment
      with 5-aza-2'-deoxycytide. RESULTS: On protein level, expression of p16(INK4a)
      was observed in undifferentiated pleomorphic sarcoma (UPS) in 69.1%,
      leiomyosarcoma in 85.7%, synovial sarcoma in 77.8%, liposarcoma in 88.9%,
      angiosarcoma in 60.9% and MPNST in 22.2%. Loss of p16(INK4a) was observed in high
      grade sarcomas and showed a significant correlation with reduced patient survival
      (p=0.032). On DNA level, one out of four sarcoma cell lines exhibited a
      methylated p16(INK4a) promoter analysed by methylation-specific PCR. p16(INK4a)
      mRNA and protein expression was restored after demethylation using 5-aza-2'
      deoxycytide. CONCLUSIONS: Upregulation of p16(INK4a) might be associated with the
      induction of senescence and indicates a senescence barrier. Downregulation of
      p16(INK4a) is found in malignant progression, and is significantly correlated
      with reduced patient survival. Downregulation of p16(INK4a) may be explained by
      DNA-hypermethylation in sarcoma cells.

PMID- 24747208
TI  - m.3635G>A mutation as a cause of Leber hereditary optic neuropathy.
AB  - Over 90% of Leber's hereditary optic neuropathy (LHON) is caused by one of three
      mtDNA mutations (m.11778A>G, m.3460G>A, m.14484T>C). The remaining cases are due
      to rare mutations in different genes encoding subunits of the respiratory chain.
      The proband is a 17-year-old male with symptoms of optic nerve atrophy. No common
      LHON mutations were found, but detailed sequencing identified a rare, homoplasmic
      mutation m.3635G>A in the ND1 gene. 

PMID- 24747209
TI  - Very mild Alzheimer's disease is characterized by increased sensitivity to
      mnemonic interference.
AB  - Early pathology and tissue loss in Alzheimer's disease (AD) occurs in the
      hippocampus, a brain region that has recently been implicated in relational
      processing irrespective of delay. Thus, tasks that involve relational processing
      will especially tax the hippocampal memory system, and should be sensitive to
      even mild dysfunction typical of early AD. Here we used a short-lag, short-delay
      memory task previously shown to be sensitive to hippocampal integrity in an
      effort to discriminate cognitive changes due to healthy aging from those
      associated with very mild AD. Young adults, healthy older adults, and individuals
      with very mild AD (N=30 for each group) participated in our investigation, which
      entailed attempting to find an exact match to a previously presented target among
      a series of stimuli that varied in perceptual similarity to the target stimulus.
      Older adults with very mild AD were less accurate than healthy older adults, who,
      in turn, were impaired relative to young adults. Older adults with very mild AD
      were also particularly susceptible to interference from intervening lure stimuli.
      A measure based on this finding was able to explain additional variance in
      differentiating those in the very mild stage of AD from healthy older adults
      after accounting for episodic memory and global cognition composite scores in
      logistic regression models. Our findings suggest that cognitive changes in early
      stage AD reflect aging along with an additional factor potentially centered on
      sensitivity to interference, thereby supporting multifactorial models of aging. 

PMID- 24747210
TI  - A close look into the near/far space division: a real-distance ERP study.
AB  - For the first time this study measures the electric brain activation in a semi
      real scenario to investigate the representation of objects in the near/far space.
      We recorded electrical brain activity from a group of 22 participants who had to
      indicate whether or not they could reach or not several objects that appeared
      along a 52" touchscreen display. We replicated previous results showing that
      reaction time to objects located in the near space was significantly faster than
      to objects located in far space. The effects of object location found here were
      significant even when their hand was not visible to them and retracted from the
      objects. ERP analysis showed a consistent N1 visual component with faster
      latencies and greater amplitudes for objects in near space. Importantly, this
      latency difference was not linked only to the physical distance but to a
      psychological division between near and far space based on their interactive
      potential (e.g. reachable vs. not reachable). At later stages LPP results showed
      significant effects of arousal at occipital electrode sites while parietal scalp
      locations were sensitive to spatial location supporting a ventral/dorsal
      dissociation of neuropsychological space. 

PMID- 24747211
TI  - Clues to maintaining calorie restriction? Psychosocial profiles of successful
      long-term restrictors.
AB  - To combat the obesity epidemic, interventions and treatments often recommend low
      calorie dieting. Calorie restriction (CR) as a weight intervention, however, is
      often unsuccessful, as most people cannot sustain the behavior. Yet one small
      group has maintained extreme CR over years - members of the CR Society and
      followers of The CR Way. This study examined stable psychosocial characteristics
      of these individuals to identify traits that may promote success at long-term CR.
      In 65 participants, we measured diet, eating behaviors, and personality traits
      comparing calorie restrictors with two age-, gender-, ethnicity-, and education
      matched comparison groups (normal weight and overweight/obese). We first tested
      whether the CR group restricted calories without indications of eating disorder
      pathology, and second, what crystallized psychosocial characteristics set them
      apart from their nonrestricting comparisons. Results indicated the CR group
      averaged 10 years of CR but scored lower than comparison groups on measures of
      disordered eating (p < .001) and psychopathology (p < .001). Particularly against
      overweight/obese participants, CR participants scored lower on neuroticism (p <
      .04) and hostility (p < .01), and were stronger in future time orientation (p <
      .05). Overall, CR profiles reflected high self-control and well being, except for
      having few close relationships. This study suggests a potential predisposition
      for successful long-term CR without disordered eating. Since modifying trait
      factors may be unrealistic, there may be psychosocial boundaries to the capacity
      for sustaining CR. Paralleling a movement toward personalized medicine, this
      study points toward a personalized behavioral medicine model in behavioral
      nutrition and treatment of overweight/obesity.

PMID- 24747212
TI  - Dietary sodium, added salt, and serum sodium associations with growth and
      depression in the U.S. general population.
AB  - It is not known why salt is so attractive to humans. Here, guided by hypotheses
      suggesting that the attraction of salt is conditioned by postingestive benefits,
      we sought to establish whether there are such benefits in a population by
      analyzing the National Health and Nutrition Examination Survey (NHANES) 2007-2008
      database (n = ~ 10,000). We focus on two potential benefits supported by the
      literature, growth and moderation of depression, and examine their relationship
      to sodium, dietary, added at table, and serum. We find that during growth (<18
      years), there is a specific increase in adjusted dietary sodium intake,
      independent of caloric or other electrolyte intakes. We find that adding salt and
      depression are related. In contrast, and in women only, dietary sodium and
      depression are inversely related. The relationships are correlational, but we
      speculate that this constellation may reflect self-medication for depression by
      adding salt, and that men may be protected by their higher dietary sodium intake.
      Additional findings are that women add more salt than men below age ~30, after
      which men add more, and below 40 years of age, serum sodium is lower in women
      than in men. It remains possible that small but beneficial effects of sodium
      could condition salt preference and thus contribute to population-wide sodium
      intake.

PMID- 24747213
TI  - Trypanosoma cruzi bromodomain factor 3 binds acetylated alpha-tubulin and
      concentrates in the flagellum during metacyclogenesis.
AB  - Bromodomains are highly conserved acetyl-lysine binding domains found mainly in
      proteins associated with chromatin and nuclear acetyltransferases. The
      Trypanosoma cruzi genome encodes at least four bromodomain factors (TcBDFs). We
      describe here bromodomain factor 3 (TcBDF3), a bromodomain-containing protein
      localized in the cytoplasm. TcBDF3 cytolocalization was determined, using
      purified antibodies, by Western blot and immunofluorescence analyses in all life
      cycle stages of T. cruzi. In epimastigotes and amastigotes, it was detected in
      the cytoplasm, the flagellum, and the flagellar pocket, and in trypomastigotes
      only in the flagellum. Subcellular localization of TcBDF3 was also determined by
      digitonin extraction, ultrastructural immunocytochemistry, and expression of
      TcBDF3 fused to cyan fluorescent protein (CFP). Tubulin can acquire different
      posttranslational modifications, which modulate microtubule functions. Acetylated
      alpha-tubulin has been found in the axonemes of flagella and cilia, as well as in
      the subpellicular microtubules of trypanosomatids. TcBDF3 and acetylated alpha
      tubulin partially colocalized in isolated cytoskeletons and flagella from T.
      cruzi epimastigotes and trypomastigotes. Interaction between the two proteins was
      confirmed by coimmunoprecipitation and far-Western blot assays with synthetic
      acetylated alpha-tubulin peptides and recombinant TcBDF3. 

PMID- 24747214
TI  - Cryptococcus neoformans dual GDP-mannose transporters and their role in biology
      and virulence.
AB  - Cryptococcus neoformans is an opportunistic yeast responsible for lethal
      meningoencephalitis in humans. This pathogen elaborates a polysaccharide capsule,
      which is its major virulence factor. Mannose constitutes over one-half of the
      capsule mass and is also extensively utilized in cell wall synthesis and in
      glycosylation of proteins and lipids. The activated mannose donor for most
      biosynthetic reactions, GDP-mannose, is made in the cytosol, although it is
      primarily consumed in secretory organelles. This compartmentalization
      necessitates specific transmembrane transporters to make the donor available for
      glycan synthesis. We previously identified two cryptococcal GDP-mannose
      transporters, Gmt1 and Gmt2. Biochemical studies of each protein expressed in
      Saccharomyces cerevisiae showed that both are functional, with similar kinetics
      and substrate specificities in vitro. We have now examined these proteins in vivo
      and demonstrate that cells lacking Gmt1 show significant phenotypic differences
      from those lacking Gmt2 in terms of growth, colony morphology, protein
      glycosylation, and capsule phenotypes. Some of these observations may be
      explained by differential expression of the two genes, but others suggest that
      the two proteins play overlapping but nonidentical roles in cryptococcal biology.
      Furthermore, gmt1 gmt2 double mutant cells, which are unexpectedly viable,
      exhibit severe defects in capsule synthesis and protein glycosylation and are
      avirulent in mouse models of cryptococcosis. 

PMID- 24747215
TI  - The spatiotemporal dynamics of early attention processes: a high-resolution
      electroencephalographic study of N2 subcomponent sources.
AB  - The N2 subcomponents of event-related potentials are known to reflect early
      attentional processes. The anterior N2 may reflect conflict monitoring, whereas
      the posterior N2 may be involved in target detection. The aim of this study was
      to identify the brain areas involved in the generation of the N2 subcomponents,
      in order to define the spatiotemporal dynamics of these attentional processes. We
      recorded 128-channel electroencephalograms in 15 healthy controls performing a
      three-stimulus visual oddball task and identified standard-, distracter- and
      target-elicited N2 components. Individual N2 sources were localized using
      standardized-weighted-low-resolution-electromagnetic-tomography (swLORETA).
      Comparative analyses were performed with a non-parametric permutation technique.
      Common N2 generators were observed in the Brodmann area (BA) 24 of the anterior
      cingulate cortex (ACC). The posterior cingulate cortex and the central precuneus
      were more involved in distracter processing, whereas the anterior precuneus and
      BA 32 of the ACC were target-specific. In accordance with previous demonstration
      of the frontoparietal cortex's critical role in attentional processes, these new
      data shed light on the ACC's role in conflict monitoring and its interaction with
      other median and frontoparietal structures in early attentional processes. 

PMID- 24747216
TI  - Equilibrium frequency of endosymbionts in multiple infections based on the
      balance between vertical transmission and cytoplasmic incompatibility.
AB  - Cytoplasmic incompatibility (CI)-inducing endosymbiotic bacteria, such as
      Wolbachia and Cardinium, have been well studied through field data and
      validations on the basis of numerical simulations. However, the analytically
      derived equilibrium frequency of multiple infections has not yet been determined,
      although the equilibrium for cases of single infection has been reported. In this
      study, we considered the difference equation for endosymbionts using three
      parameters: the probability of the failure of vertical transmission ([Formula:
      see text]), CI strength ([Formula: see text]), and the level of host inbreeding
      ([Formula: see text]). To analyze this model, we particularly focused on
      [Formula: see text], i.e., the frequency of host individuals completely infected
      with all [Formula: see text]-bacterial strains in the population. [Formula: see
      text], [Formula: see text] at the equilibrium state, was analytically calculated
      in the cases where [Formula: see text] and [Formula: see text] is any arbitrary
      value. We found that [Formula: see text] can be described using two parameters:
      [Formula: see text] and [Formula: see text], which is identical to [Formula: see
      text]. [Formula: see text] has a larger value in a system with a smaller
      [Formula: see text]. In addition, [Formula: see text] determines the maximum
      number of strains that infect a single host. Our results revealed the following:
      i) three parameters can be reduced to a single parameter, i.e., [Formula: see
      text] and ii) the threshold of the maximum number of infections is defined by
      [Formula: see text], which prevents additional invasions by endosymbionts. 

PMID- 24747218
TI  - Pro-angiogenic impact of dental stem cells in vitro and in vivo.
AB  - Within the field of dental tissue engineering, the establishment of adequate
      tissue vascularization is one of the most important burdens to overcome. As
      vascular access within the tooth is restricted by the apical foramen, it is of
      major importance to implement effective vascularization strategies in order to
      recreate viable components of teeth and periodontal tissues. However, while the
      current regenerative approaches focus on the use of dental stem cells (DSCs),
      little is known about these cells and their ability to promote angiogenesis.
      Therefore, the present study aimed to elucidate the paracrine angiogenic
      properties of postnatal DSCs, in particular dental pulp stem cells (DPSCs), stem
      cells from the apical papilla (SCAPs) and dental follicle precursor cells (FSCs).
      An antibody array, together with RT-PCR and ELISA, pointed out the differential
      expression of pro-angiogenic as well as anti-angiogenic factors by cultured DSCs
      and human gingival fibroblasts (HGF-1). Despite the secretion of proliferation
      promoting factors, DSCs caused no notable increase in the proliferation of human
      microvascular endothelial cells (HMEC-1). With regard to other aspects of the
      angiogenic cascade, DPSCs, SCAPs and HGF-1 significantly promoted endothelial
      migration in a transwell migration assay. DPSCs also had a pronounced effect on
      endothelial tubulogenesis, as was shown by an in vitro MatrigelTM assay. In the
      last part of this study, a chorioallantoic membrane assay demonstrated a
      sustained pro-angiogenic impact of DPSCs and SCAPs in an in vivo setting.
      Collectively, these data indicate a predominant pro-angiogenic influence of DPSCs
      and SCAPS in vitro and in vivo in comparison to FSCs, suggesting that both stem
      cell populations could potentially promote the vascularization of regenerated
      dental tissues. 

PMID- 24747219
TI  - DSRC 2--Industry-oriented compression of FASTQ files.
AB  - SUMMARY: Modern sequencing platforms produce huge amounts of data. Archiving them
      raises major problems but is crucial for reproducibility of results, one of the
      most fundamental principles of science. The widely used gzip compressor, used for
      reduction of storage and transfer costs, is not a perfect solution, so a few
      specialized FASTQ compressors were proposed recently. Unfortunately, they are
      often impractical because of slow processing, lack of support for some variants
      of FASTQ files or instability. We propose DSRC 2 that offers compression ratios
      comparable with the best existing solutions, while being a few times faster and
      more flexible. AVAILABILITY AND IMPLEMENTATION: DSRC 2 is freely available at
      http://sun.aei.polsl.pl/dsrc. The package contains command-line compressor, C and
      Python libraries for easy integration with existing software and technical
      documentation with examples of usage. CONTACT: sebastian.deorowicz@polsl.pl
      SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics
      online.

PMID- 24747217
TI  - VGF (TLQP-62)-induced neurogenesis targets early phase neural progenitor cells in
      the adult hippocampus and requires glutamate and BDNF signaling.
AB  - The neuropeptide VGF (non-acronymic), which has antidepressant-like effects,
      enhances adult hippocampal neurogenesis as well as synaptic activity and
      plasticity in the hippocampus, however the interaction between these processes
      and the mechanism underlying this regulation remain unclear. In this study, we
      demonstrate that VGF-derived peptide TLQP-62 specifically enhances the generation
      of early progenitor cells in nestin-GFP mice. Specifically, TLQP-62 significantly
      increases the number of Type 2a neural progenitor cells (NPCs) while reducing the
      number of more differentiated Type 3 cells. The effect of TLQP-62 on
      proliferation rather than differentiation was confirmed using NPCs in vitro; TLQP
      62 but not scrambled peptide PEHN-62 increases proliferation in a cell line as
      well as in primary progenitors from adult hippocampus. Moreover, TLQP-62 but not
      scrambled peptide increases Cyclin D mRNA expression. The proliferation of NPCs
      induced by TLQP-62 requires synaptic activity, in particular through NMDA and
      metabotropic glutamate receptors. The activation of glutamate receptors by TLQP
      62 activation induces phosphorylation of CaMKII through NMDA receptors and
      protein kinase D through metabotropic glutamate receptor 5 (mGluR5). Furthermore,
      pharmacological antagonists to CaMKII and PKD inhibit TLQP-62-induced
      proliferation of NPCs indicating that these signaling molecules downstream of
      glutamate receptors are essential for the actions of TLQP-62 on neurogenesis. We
      also show that TLQP-62 gradually activates Brain-Derived Neurotrophic Factor
      (BDNF)-receptor TrkB in vitro and that Trk signaling is required for TLQP-62
      induced proliferation of NPCs. Understanding the precise molecular mechanism of
      how TLQP-62 influences neurogenesis may reveal mechanisms by which VGF-derived
      peptides act as antidepressant-like agents. 

PMID- 24747220
TI  - Herpesviral helicase-primase subunit UL8 is inactivated B-family polymerase.
AB  - MOTIVATION: Herpesviruses are large DNA viruses causing a variety of diseases in
      humans and animals. To develop effective treatment, it is important to understand
      the mechanisms of their replication. One of the components of the herpesviral DNA
      replication system is a helicase-primase complex, consisting of UL5 (helicase),
      UL52 (primase) and UL8. UL8 is an essential herpesviral protein involved in
      multiple protein-protein interactions. Intriguingly, so far no UL8 homologs
      outside of herpesviruses could be identified. Moreover, nothing is known about
      its structure or domain organization. RESULTS: Here, combining sensitive homology
      detection methods and homology modeling, we found that the UL8 protein family is
      related to B-family polymerases. In the course of evolution, UL8 has lost the
      active site and has undergone a reduction of DNA-binding motifs. The loss of
      active site residues explains the failure to detect any catalytic activity of
      UL8. A structural model of human herpes virus 1 UL8 constructed as part of the
      study is consistent with the mutation data targeting its interaction with primase
      UL52. It also provides a platform for studying multiple interactions that UL8 is
      involved in. The two other components of helicase-primase complex show
      evolutionary links with a newly characterized human primase that also has DNA
      polymerase activity (PrimPol) and the Pif1 helicase, respectively. The role of
      these enzymes in recovering stalled replication forks suggests mechanistic and
      functional similarities with herpesviral proteins. CONTACT: venclovas@ibt.lt
      SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics
      online.

PMID- 24747222
TI  - Symptom incongruence trajectories in lung cancer dyads.
AB  - CONTEXT: There is little known about the pattern of change in patient-family
      member symptom incongruence across the lung cancer trajectory. OBJECTIVES: This
      study examined trajectories of patient-family member incongruence in perceptions
      of patient physical function, pain severity, fatigue, and dyspnea in lung cancer
      dyads and explored the association with family member grief after patient death.
      METHODS: Lung cancer patients and their family members providing care (n = 109
      dyads) rated patient symptoms and physical function five times over 12 months.
      Symptom incongruence trajectories were analyzed using multilevel modeling.
      RESULTS: Patient-family member incongruence did not significantly change over
      time, on average, except in the case of patient physical function where
      incongruence significantly declined. There was significant variability around
      trajectories of incongruence for all symptoms except fatigue. Exploratory
      analysis on a subsample of 22 bereaved family members found that incongruence
      regarding patient fatigue was associated with family member grief two months
      after patient death. CONCLUSION: Findings suggest the importance of modeling
      symptom incongruence over time and taking a dyadic approach to the illness
      context to identify interventions that promote adjustment and quality of life for
      both patient and family member.

PMID- 24747221
TI  - Acrolein-exposed normal human lung fibroblasts in vitro: cellular senescence,
      enhanced telomere erosion, and degradation of Werner's syndrome protein.
AB  - BACKGROUND: Acrolein is a ubiquitous environmental hazard to human health.
      Acrolein has been reported to activate the DNA damage response and induce
      apoptosis. However, little is known about the effects of acrolein on cellular
      senescence. OBJECTIVES: We examined whether acrolein induces cellular senescence
      in cultured normal human lung fibroblasts (NHLF). METHODS: We cultured NHLF in
      the presence or absence of acrolein and determined the effects of acrolein on
      cell proliferative capacity, senescence-associated beta-galactosidase activity,
      the known senescence-inducing pathways (e.g., p53, p21), and telomere length.
      RESULTS: We found that acrolein induced cellular senescence by increasing both
      p53 and p21. The knockdown of p53 mediated by small interfering RNA (siRNA)
      attenuated acrolein-induced cellular senescence. Acrolein decreased Werner's
      syndrome protein (WRN), a member of the RecQ helicase family involved in DNA
      repair and telomere maintenance. Acrolein-induced down-regulation of WRN protein
      was rescued by p53 knockdown or proteasome inhibition. Finally, we found that
      acrolein accelerated p53-mediated telomere shortening. CONCLUSIONS: These results
      suggest that acrolein induces p53-mediated cellular senescence accompanied by
      enhanced telomere attrition and WRN protein down-regulation.

PMID- 24747223
TI  - Improving communication on hope in palliative care. A qualitative study of
      palliative care professionals' metaphors of hope: grip, source, tune, and vision.
AB  - CONTEXT: Hope is important in palliative care. However, palliative care
      professionals' perspectives on hope are not well understood. Metaphors of hope
      are a way of better understanding these perspectives. OBJECTIVES: To describe
      palliative care professionals' perspectives on hope by examining the hope
      metaphors they spontaneously used to describe their own hope and their
      perspectives on the hope of patients and their families. METHODS: Semistructured
      interviews with palliative care professionals were recorded, transcribed, and
      analyzed using a narrative approach. Results were discussed until the researchers
      reached consensus and reinforced by other health-care professionals and by
      observing several palliative care settings. RESULTS: The 64 participants (mean
      (SD) age, 48.42 (9.27) years and 72% female) were physicians (41%), nurses (34%),
      chaplains (20%), or other professionals (5%), working in Canada (19%) or The
      Netherlands (81%). Participants described the hope of patients, their families,
      or themselves as a 1) grip, which implied safety; 2) source, which implied
      strength; 3) tune, which implied harmony; and 4) vision, which implied a positive
      perspective. Compared with Dutch participants, Canadian participants generally
      put more emphasis on spirituality and letting go of their own hope as a grip
      (safety). Compared with other included professionals, physicians used hope as a
      grip (safety) most often, whereas chaplains used hope as a tune (harmony) most
      often. CONCLUSION: Our findings help to increase the understanding of hope and
      contribute to improving communication skills in palliative care professionals.

PMID- 24747224
TI  - Clinical impact of a home-based palliative care program: a hospice-private payer
      partnership.
AB  - CONTEXT: Outpatient programs have been traditionally offered in the U.S. under
      programs such as the Medicare Hospice Benefit. Recommendations now emphasize a
      blended model in which palliative care is offered concurrently with curative
      approaches at the onset of serious or life-limiting disease. The efficacy of
      nonhospice outpatient palliative care programs is not well understood.
      OBJECTIVES: The aim of the study was to evaluate the clinical impact of a home
      based palliative care program, Home Connections, implemented as a partnership
      between a not-for-profit hospice and two private insurers. METHODS: This was a
      prospective, observational, database study of 499 Home Connections participants
      enrolled between July 1, 2008, and May 31, 2013. Measured outcomes were advance
      directive completion, site of death, symptom severity over time, program
      satisfaction, and hospice referral and average length of stay. RESULTS: Seventy
      one percent of participants completed actionable advance directives after
      enrollment, and the site of death was home for 47% of those who died during or
      after participation in the program. Six of eight symptom domains (anxiety,
      appetite, dyspnea, well-being, depression, and nausea) showed improvement.
      Patients, caregivers, and physicians gave high program satisfaction scores (93%
      96%). Home Connections participants who subsequently enrolled in hospice care had
      a longer average length of stay of 77.9 days compared with all other hospice
      referrals (average length of stay 56.5 days). CONCLUSION: A home-based palliative
      care program was developed between two local commercial payers and a not-for
      profit hospice. Not only did this program improve symptom management, advance
      directive completion, and satisfaction, but it also facilitated the transition of
      patients into hospice care, when appropriate.

PMID- 24747225
TI  - Is race/ethnicity related to the presence or severity of pain in colorectal and
      lung cancer?
AB  - CONTEXT: Developing interventions to address racial/ethnic cancer pain
      disparities requires exploration of the role of socioeconomic status, health
      status, and pain severity from the time of diagnosis. OBJECTIVES: To examine
      patterns of disparities in cancer pain by evaluating differences by
      race/ethnicity in the odds of reporting pain and in pain severity, controlling
      for key patient-level covariates. METHODS: This study used data from a nationally
      representative cohort of colorectal and lung cancer patients. Multivariable
      logistic regression was conducted to examine the relationship between
      race/ethnicity and reporting pain. Multivariable linear regression was then
      conducted, among those who reported pain, to determine differences in pain
      severity by race/ethnicity. RESULTS: The cohort included 5761 individuals (14%
      black, 7% Hispanic/Latino, 6% Asian or Pacific Islander, and 3% multiracial),
      among whom 48% reported pain. The adjusted odds of reporting differed only for
      multiracial patients, who were more likely to report pain than whites (odds
      ratio: 1.54; P = 0.036). However, among those with pain, severity was higher for
      black patients (beta = 6.6; P <= 0.001) and multiracial patients (beta = 4.5; P =
      0.036) relative to white patients. Lower educational attainment, depressed
      affect, and lower levels of wealth also were associated with higher pain
      severity. CONCLUSION: Although the odds of experiencing pain differed only for
      multiracial patients, among those reporting pain, both blacks and multiracial
      individuals reported higher pain severity than whites. Sociodemographic status,
      health status, and depression were associated with severity but did not explain
      the disparity. Interventions to address these disparities will need to focus on
      reported severity and patient-level factors.

PMID- 24747226
TI  - Cancer symptom clusters: an exploratory analysis of eight statistical techniques.
AB  - CONTEXT: Statistical methods to identify symptom clusters (SC) have varied
      between studies. The optimal statistical method to identify SC is unknown.
      OBJECTIVES: Our primary objective was to explore whether eight different
      statistical techniques applied to a single data set produced different SC. A
      secondary objective was to investigate whether SC identified by these techniques
      resembled those from our original study. METHODS: We reanalyzed a symptom data
      set of 1000 patients with advanced cancer. Eight separate cluster analyses were
      conducted on both prevalence and severity of 38 symptoms. Hierarchical cluster
      analysis identified clusters at r-values of 0.6, 0.5, and 0.4. For prevalence and
      severity, the Spearman correlation and Kendall tau-b correlation, respectively,
      measured the similarity (distance) between symptom pairs. Sensitivity analysis of
      the prevalence data was done with Cohen kappa coefficient as a similarity
      measure. The K-means clustering method validated clusters. RESULTS: Hierarchical
      cluster analysis identified similar cluster configurations from the 38 symptoms
      using an r-value of 0.6, 0.5, or 0.4. A cutoff point of 0.6 yielded seven
      clusters. Five of them were identical at all three r-values used: (1)
      fatigue/anorexia-cachexia: anorexia, dry mouth, early satiety, fatigue, lack of
      energy, taste changes, weakness, and weight loss (>10%); (2) gastrointestinal:
      belching, bloating, dyspepsia, and hiccough; (3) nausea/vomiting: nausea and
      vomiting; (4) aerodigestive: cough, dysphagia, dyspnea, hoarseness, and wheeze;
      (5) neurologic: confusion, hallucinations, and memory problems. Regardless of the
      threshold, there were always some symptoms (e.g., pain) that did not cluster with
      any others. Seven clusters were validated by K-means analysis. CONCLUSION: Seven
      SC identified from both prevalence and severity data were consistently present
      irrespective of the statistical analysis used. There were only minor variations
      in the number of clusters and their symptom composition between analytical
      techniques. All seven clusters originally identified were confirmed. Four
      consistent SC were found in all analyses: aerodigestive, fatigue/anorexia
      cachexia, nausea/vomiting, and upper GI. Our results support the clinical
      importance of the SC concept.

PMID- 24747228
TI  - Intelligent pharmaceuticals: beyond the tipping point.
AB  - Confluences of key factors can transform apparently isolated or random events
      into trends. The ongoing and growing pressures facing the pharmaceutical industry
      have "tipped" the industry toward a new direction in the choice of which new
      medicines to develop and how to develop them. We examine the factors that are at
      the tipping point. 

PMID- 24747231
TI  - Recent trends and success factors in reducing the lag time to approval of new
      drugs in Japan.
AB  - For many years, approvals of new drugs in Japan have lagged behind those in the
      United States and Europe. As a result of simultaneous global development
      strategies, more widespread inclusion of Japan in multiregional clinical trials,
      and significant reforms and investment in Japan's Pharmaceuticals and Medical
      Devices Agency reviewer capacity and capability, the drug lag appears to be
      diminishing. This is allowing new medicines to be approved sooner in Japan,
      improving the efficiency of drug development and benefiting patients. 

PMID- 24747232
TI  - Promise and challenges with the use of mobile applications to support and improve
      patient care: an industry perspective.
AB  - Mobile applications represent an immense opportunity to support and improve
      patient health care, as the scope and functionality of medical apps are enabling
      physicians and patients to manage care in new, fast, and personalized ways.
      Several challenges exist in medical-app development, including careful attention
      to quality systems, medical-device regulation, and app life span. Despite these
      complexities, we find that development of mobile medical apps is a worthwhile
      undertaking given their potential to improve outcomes for patients. 

PMID- 24747233
TI  - The role of academic medical centers in advancing regulatory science.
AB  - The US Food and Drug Administration (FDA) has oversight of an increasingly
      complex array of therapeutic and scientific advances, as well as an expanded
      mission that now includes enabling innovation. This complex mission necessitates
      access to and understanding of relevant scientific expertise in what is commonly
      called "regulatory science." Academic medical centers have much of this relevant
      expertise, and there is an increasing need and opportunity for the FDA to engage
      with them to shape the regulatory science agenda.

PMID- 24747234
TI  - Itraconazole and clarithromycin as ketoconazole alternatives for clinical CYP3A
      inhibition studies.
AB  - High-dose ketoconazole (400 mg q.d. for >=5 days) has been the gold-standard
      strong cytochrome P450 3A (CYP3A) inhibitor in drug development drug-drug
      interaction (DDI) studies. In 2013, the US Food and Drug Administration (FDA) and
      the European Medicines Agency (EMA) advised against using this ketoconazole
      regimen following review of clinical safety reports. We systematically evaluated
      19 strong CYP3A inhibitors from regulatory guidances and a literature database to
      identify itraconazole (200 mg b.i.d. on day 1, q.d. on days 2-6) and
      clarithromycin (500 mg b.i.d. for 7 days) as acceptable ketoconazole
      alternatives.

PMID- 24747235
TI  - Mobile medical applications: old wine in new bottles?
AB  - In Her, the award-winning motion picture written and directed by Spike Jonze, the
      lead character played by Joaquin Phoenix falls hopelessly in love with an
      operating system deployed on his many devices, including his mobile telephone.
      Although the health-care sector has not yet attained that "magic moment" with
      mobile devices and their applications, there appears to be quite a lot for those
      in the field to like. 

PMID- 24747236
TI  - Physiologically based pharmacokinetic modeling: from regulatory science to
      regulatory policy.
AB  - Assessment of controllable sources of intra- and interpatient variability in drug
      response is of critical importance in the regulatory evaluation of new drugs.(1)
      Although determinants of response variability would ideally be understood and
      accounted for before approval of a new pharmaceutical product, this is rarely the
      case for all; clinical trials in specific populations that definitively test
      optimal dosing in patient management strategies are not routinely performed prior
      to drug approval. 

PMID- 24747237
TI  - Modeling and simulation of biopharmaceutical performance.
AB  - Biopharmaceutical performance refers to the influence of pharmaceutical
      formulation variables on in vivo performance. New drug product success depends on
      formulation design for sufficient bioavailability for clinically desired dosing.
      Regulatory interest in biopharmaceutical performance includes batch-to-batch
      consistency, acceptability of postapproval changes, and evaluation of
      bioequivalence (BE) for generic drug products. This Commentary summarizes
      biopharmaceutical modeling and simulation in the US Food and Drug Administration
      (FDA) Office of Generic Drugs (OGD) for orally administered generic drugs.

PMID- 24747238
TI  - Drug development in serious diseases: the new "breakthrough therapy" designation.
AB  - The US Food and Drug Administration Safety and Innovation Act (FDASIA) was signed
      on 9 July 2012. This law created a new "breakthrough therapy" (BT) designation
      program for investigational drugs and biologics intended to treat a serious
      disease and having "preliminary clinical evidence [that] indicates that the drug
      may demonstrate substantial clinical improvement over existing therapies on one
      or more clinically significant endpoints."(1) Many questions have been posed
      about the impact of this new program on drug development. 

PMID- 24747239
TI  - The FDA's role in the development of medical mobile applications.
AB  - The use of mobile apps is revolutionizing health-care delivery and has the
      potential to transform health care by allowing doctors to diagnose patients with
      potentially life-threatening conditions outside traditional health-care settings,
      as well as helping consumers manage their own health and wellness and gain access
      to useful information when and where they need it. 

PMID- 24747240
TI  - Differential expression of anterior gradient protein 3 in intrahepatic
      cholangiocarcinoma and hepatocellular carcinoma.
AB  - Intrahepatic cholangiocarcinoma (ICC) is the second most common primary liver
      cancer next to hepatocellular carcinoma (HCC). Despite the significant difference
      of the therapeutic strategy for both diseases, their histological appearance may
      be very similar. Thus the correct diagnosis is crucial for treatment choice but
      is often difficult to achieve. The aim of our study was to evaluate anterior
      gradient 3 (AGR3) as a new diagnostic marker helping to distinguish between ICC
      and HCC. AGR3 is a putative transmembrane protein implicated in breast, prostate
      and ovary tumorigenesis and belongs to the family of protein disulfide
      isomerases. Since there is little information on how AGR3 is expressed in normal
      and diseased tissues and what its exact function is, we analyzed its expression
      pattern in normal liver and tumor tissue of ICC and HCC. The immunohistochemical
      analysis in normal tissue revealed specific AGR3 expression in intrahepatic bile
      duct cholangiocytes which was not present in liver hepatocytes. Consequently we
      analyzed AGR3 expression in 74 representative samples of puncture biopsies,
      tissue excisions and resection specimens from which 48 samples were diagnosed as
      HCC and 26 as ICC. Our results showed AGR3 expression negative and weakly
      positive respectively in hepatocellular carcinomas compared to stronger AGR3
      positivity in cholangiocellular carcinomas. AGR3 expression statistically
      significantly correlated to acid mucopolysaccharide expression and negatively
      correlated to glypican-3 expression. We conclude that according to receiver
      operating characteristics (ROC) analysis AGR3 expression is relatively specific
      for ICC and is potentially linked to mucosecretion, which may indicate potential
      implication in treatment resistance. 

PMID- 24747242
TI  - Obesity-mediated association between exposure to brominated trihalomethanes and
      type II diabetes mellitus: an exploratory analysis.
AB  - With the exception of chloroform, the rest of trihalomethanes (THM), the so
      called brominated THM (Br-THM) are composed of bromine-substituted molecules with
      increased lipophilicity and potency to biological tissues. The THM are formed
      within disinfected tap water and their health effects, under research, range from
      cancer to adverse reproductive outcomes. However, the association between human
      exposures to Br-THM and the risk of developing type II diabetes mellitus (T2DM)
      and metabolic co-morbidities, such as obesity and non-alcoholic steatohepatitis
      has never been previously explored. The objective of this exploratory analysis
      was to address obesity-mediated associations between urinary concentrations of
      brominated THM and incidences of T2DM in a Cypriot adult population (n=326).
      First morning urine voids were collected once during summer and another time
      during winter while a detailed questionnaire was administered to participants.
      Creatinine-adjusted urinary Br-THM analyte concentrations were significantly
      (p<0.05) higher in T2DM cases when compared with those in healthy individuals.
      Multivariate logistic regression models adjusted for potential confounders showed
      that participants with >=30 kg m(-2) BMI were at a higher T2DM risk (OR=8.42, 95%
      CI: 1.97, 45.5; p<0.01) when compared with that of normal weight participants
      (<25 kg m(-2)). About 4 times higher risk for developing T2DM was observed for
      individuals in the upper tertile of urinary Br-THM levels (OR=3.99, 95% CI: 1.07,
      19.7; p<0.05) when compared with the lower tertile participants. Among the
      participants with BMI>=25 kg m(-2), urinary Br-THM levels were significantly
      (p<0.001) higher in diabetics than in healthy individuals. Ingestion and non
      ingestion exposures to Br-THM deserve careful consideration in relevant
      epidemiological studies, as a possible environmental risk factor of T2DM.

PMID- 24747241
TI  - M1- and M2-macrophage polarization in rat liver cirrhosis induced by
      thioacetamide (TAA), focusing on Iba1 and galectin-3.
AB  - INTRODUCTION: Resident and exudate macrophages play an important role in the
      development of liver cirrhosis. Ionized calcium binding adaptor molecule 1(+)
      (Iba1(+)) and galectin-3(+) (Gal-3(+)) macrophages regulate liver fibrosis
      probably through pro-inflammatory and pro-fibrotic factors. Macrophages show
      polarized functions in liver fibrosis; however, M1-/M2-polarization of Iba1(+)
      and Gal-3(+) macrophages remains obscured. This study investigated the M1-/M2
      polarized properties of Iba1(+) and Gal-3(+) macrophages in chemical-induced
      liver cirrhosis. MATERIALS AND METHODS: Cirrhosis was induced in F344 rats by
      repeated injections of thioacetamide (100mg/kg BW, twice a week for 25 weeks).
      Liver samples were collected from post-first-injection (PFI) week 5 to 25.
      Macrophage immunophenotypes and myofibroblasts in the fibrous bridges (FBs) and
      pseudolobules (PLs) were analyzed by immunohistochemistry. Expressions of M1- and
      M2-related factors were analyzed with RT-PCR, separately in FBs and PLs. RESULTS:
      Activation of myofibroblasts was most pronounced in livers at week 15. CD68(+)
      (M1), CD204(+) (M2), Iba1(+) and Gal-3(+) macrophages in the FBs increased
      gradually and peaked at week 15, consistent with the upregulation of both M1-(MCP
      1, IFN-gamma, IL-1beta, IL-6, and TNF-alpha) and M2-(TGF-beta1, IL-4, and IL-10)
      related factors. Iba1(+) and Gal-3(+) macrophages showed both M1- and M2
      immunophenotypes. CD163(+) macrophages showed a persistent increase, consistent
      with TGF-beta1 upregulation. MHC class II(+) macrophages increased in the
      developing fibrotic lesions, and then reduced in the advanced stage cirrhosis.
      CONCLUSION: Both M1- and M2-macrophage polarizations occur during development of
      liver cirrhosis. Iba1(+) and Gal-3(+) macrophages participate in liver cirrhosis
      through production of both M1- and M2-related factors.

PMID- 24747244
TI  - Spectroscopic measurements of estuarine dissolved organic matter dynamics during
      a large-scale Mississippi River flood diversion.
AB  - The Mississippi River Flood of 2011 prompted the opening of the Bonnet Carre
      Spillway (BCS) in southeastern Louisiana to protect the City of New Orleans. The
      BCS diverted approximately 21.9 km(3) of river water into the oligohaline Lake
      Pontchartrain Estuary over the course of 43 days. We characterized estuarine
      dissolved organic matter (DOM) dynamics before, during, and after the diversion
      in order to better understand the biogeochemical dynamics associated with these
      immense freshwater inflows. Dissolved organic carbon (DOC) exhibited a large
      degree of variability during and after the period of elevated primary
      productivity that occurred following the diversion. Furthermore, DOC analysis
      provides limited insight into carbon cycling during these dynamic periods. In
      order to overcome the limitations of DOC, spectroscopic methods were used to gain
      insights into chemical composition dynamics. Both ultraviolet visible (A254,
      A350, SUVA254, spectral slope, and normalized UV/Vis) and fluorescence
      spectroscopy (excitation emission matrices and fluorescence and biological
      indices) were used to study the compositional changes of DOM over time.
      Collectively, our results document a perturbation in DOM chemistry in Lake
      Pontchartrain due to the diversion and a subsequent return toward pre-diversion
      conditions. Immediate increases in A350 indicate that BCS freshwater contained
      elevated concentrations of lignin of terrestrial origin. Ensuing declines in
      A350, along with changes in the fluorescence and biological indices, indicate
      that DOM rapidly became more microbial in composition. Our results provide
      insights into estuarine DOM dynamics relevant to systems receiving flood pulses
      of freshwater due to either hydrologic manipulation or precipitation events.

PMID- 24747245
TI  - Urban stormwater inputs to an adapted coastal wetland: role in water treatment
      and impacts on wetland biota.
AB  - The Lake Pertobe wetland system is a semi-natural wetland that has been modified
      primarily for recreational use. However, this lake system receives stormwater
      from much of the central business district of Warrnambool City (Victoria,
      Australia) and serves as a buffer zone between the stormwater system and the
      Merri River and Merri Marine Sanctuary. This work considers the impact of
      stormwater inputs on Lake Pertobe and the effectiveness of the lake in protecting
      the associated marine sanctuary. Sediment contaminants (including heavy metals
      and polycyclic aromatic hydrocarbons (PAHs)) and water quality parameters within
      the lake, groundwater and stormwater system were measured. Water quality
      parameters were highly variable between stormwater drains and rain events.
      Suspended solids rapidly settled along open drains and shortly after entering the
      lake. Groundwater inputs increased both salinity and dissolved nitrogen in some
      stormwater drains. Some evidence of bioaccumulation of metals in the food chain
      was identified and sediment concentrations of several PAHs were very high. The
      lake acted as a sink for PAHs and some metals and reductions in Escherichia coli,
      biological oxygen demand and total phosphorus were observed, affording some
      protection to the associated marine sanctuary. Nutrient retention was inadequate
      overall and it was identified that managing the lake primarily as a recreational
      facility impacted on the effectiveness of stormwater treatment in the system. 

PMID- 24747246
TI  - Effects of Barcelona harbor sediments in biological responses of the polychaete
      Capitella teleta.
AB  - Marine ecosystems are increasingly exposed to a multitude of anthropogenic
      contaminants. Harbor environments are permanently subjected to such contaminants
      and bottom sediments are considered as the final repository. Filter-feeding and
      burrowing organisms, such as some polychaete communities, are among the most
      exposed organisms. This study aimed to assess the toxicity of Barcelona harbor
      sediments to the polychaete Capitella teleta by assessing and linking individual
      level responses such as body weight (growth) and egestion rate (feeding) with
      subcellular-level responses including antioxidant (catalase and superoxide
      dismutase) and neurotransmission related (acetyl cholinesterase) enzyme
      activities. Sediments were collected from three different locations of the
      Barcelona (Spain) harbor with a positive gradient of metallic and organochlorine
      pollution from the mouth of the harbor towards the innermost zone. Sub-cellular
      and individual behavior of C. teleta exposed to Barcelona harbor sediments
      allowed the discrimination of toxic responses across sediments. Behavior
      responses were better correlated to chemical contamination than those of
      biomarkers. Harbor sediments produced neurotoxicity, promoted oxidative stress
      and reduced egestion and growth rates in exposed worms. These results indicate
      that biological responses of C. teleta worm can be used as early-warning tools to
      assess pollution effects on marine soft-bottom macrobenthonic communities. 

PMID- 24747247
TI  - Environmental impact of intensive aquaculture: investigation on the accumulation
      of metals and nutrients in marine sediments of Greece.
AB  - The impact of intensive aquaculture activities on marine sediments along three
      coastal areas in Greece was studied. The content of nine metals/metalloids (Cu,
      Cd, Pb, Hg, Ni, Fe, Mn, Zn, As), and three nutrients (P, N and C), that seem to
      accumulate in marine sediments, was determined under the fish cages (zero
      distance) and away (50 or 100 m) from them. Elevated concentrations for
      phosphorus, nitrogen, copper, zinc and cadmium were recorded in the areas where
      farming establishments are moored. In parallel, the intrinsic differences between
      the aquaculture facilities and their seasonal variations were investigated. The
      individual characteristics of each farm (local water currents, facilities'
      capacity, transferring mechanisms or the geological background) were the
      determinant factors. On the contrary, significant seasonal differences were not
      recorded. Statistical techniques, as the non-parametric Mann-Whitney U and
      Kruskal-Wallis tests and principal components analysis (PCA), factor analysis
      (FA) and discriminant analysis (DA), were used for the evaluation of the results.
      These chemometric tools succeeded to discriminate the sampling points according
      to their distance from the cages or the origin of the sample. Variables'
      significance, correlations and potential accumulation sources were also
      investigated.

PMID- 24747248
TI  - Evaluation of observation-fused regional air quality model results for population
      air pollution exposure estimation.
AB  - In this study, Community Multiscale Air Quality (CMAQ) model was applied to
      predict ambient gaseous and particulate concentrations during 2001 to 2010 in 15
      hospital referral regions (HRRs) using a 36-km horizontal resolution domain. An
      inverse distance weighting based method was applied to produce exposure estimates
      based on observation-fused regional pollutant concentration fields using the
      differences between observations and predictions at grid cells where air quality
      monitors were located. Although the raw CMAQ model is capable of producing
      satisfying results for O3 and PM2.5 based on EPA guidelines, using the
      observation data fusing technique to correct CMAQ predictions leads to
      significant improvement of model performance for all gaseous and particulate
      pollutants. Regional average concentrations were calculated using five different
      methods: 1) inverse distance weighting of observation data alone, 2) raw CMAQ
      results, 3) observation-fused CMAQ results, 4) population-averaged raw CMAQ
      results and 5) population-averaged fused CMAQ results. It shows that while O3 (as
      well as NOx) monitoring networks in the HRRs are dense enough to provide
      consistent regional average exposure estimation based on monitoring data alone,
      PM2.5 observation sites (as well as monitors for CO, SO2, PM10 and PM2.5
      components) are usually sparse and the difference between the average
      concentrations estimated by the inverse distance interpolated observations, raw
      CMAQ and fused CMAQ results can be significantly different. Population-weighted
      average should be used to account for spatial variation in pollutant
      concentration and population density. Using raw CMAQ results or observations
      alone might lead to significant biases in health outcome analyses. 

PMID- 24747249
TI  - The thermal consequences of river-level variations in an urban groundwater body
      highly affected by groundwater heat pumps.
AB  - The extensive implementation of ground source heat pumps in urban aquifers is an
      important issue related to groundwater quality and the future economic
      feasibility of existent geothermal installations. Although many cities are in the
      immediate vicinity of large rivers, little is known about the thermal river
      groundwater interaction at a kilometric-scale. The aim of this work is to
      evaluate the thermal impact of river water recharges induced by flood events into
      an urban alluvial aquifer anthropogenically influenced by geothermal
      exploitations. The present thermal state of an urban aquifer at a regional scale,
      including 27 groundwater heat pump installations, has been evaluated. The thermal
      impacts of these installations in the aquifer together with the thermal impacts
      from "cold" winter floods have also been spatially and temporally evaluated to
      ensure better geothermal management of the aquifer. The results showed a variable
      direct thermal impact from 0 to 6  degrees C depending on the groundwater-surface
      water interaction along the river trajectory. The thermal plumes far away from
      the riverbed also present minor indirect thermal impacts due to hydraulic
      gradient variations.

PMID- 24747243
TI  - 'Core species' in three sources of indoor air belonging to the human micro
      environment to the exclusion of outdoor air.
AB  - Although we spend the majority of our lives indoors, the airborne microbial
      content of enclosed spaces still remains inadequately described. The objective of
      this study was to characterize the bacterial diversity of indoor air in three
      different enclosed spaces with three levels of occupancy, and, in particular, to
      highlight the 'core' species, the opportunistic pathogens and their origins. Our
      findings provide an overall description of bacterial diversity in these indoor
      environments. Data gathered from the three enclosed spaces revealed the presence
      of a common indoor signature (60% of total sequences in common). This work will
      provide a clearer understanding of the dominant groups of bacteria encountered in
      enclosed spaces: Actinobacteria, Proteobacteria, Firmicutes and Bacteroidetes.
      Thus, certain evidence revealed a connection between 'core' species and the human
      micro-environment (20% of phylotypes and 12% of sequences of human origin).
      Overall PCA analysis showed that the indoor environment is influenced mainly by
      the microbial diversity from nose and skin. Among the 'core species' found during
      this study, a large number (72% of all pathogen-related sequences were
      concentrated in 'core species') of genera and species are known to be responsible
      for opportunistic or nosocomial diseases or to include human commensal bacteria
      such as Mycobacterium sp., Acinetobacter baumanii, Aerococcus viridians,
      Thermoactinomyces vulgaris or Clostridium perfringens. 

PMID- 24747250
TI  - Resolution of the mediators of in vitro oxidative reactivity in size-segregated
      fractions that may be masked in the urban PM(10) cocktail.
AB  - PM10 (particulate matter 10 MUm or less in aerodynamic diameter) has consistently
      been linked with adverse human health effects, but the physicochemical properties
      responsible for this effect have not been fully elucidated. The aim of this work
      was to investigate the potential for carbon black (CB) particles and PM to
      generate ROS (Reactive Oxygen Species) and to identify the physicochemical
      properties of the particles responsible for in vitro oxidative reactivity (OR).
      PM10 was collected in 11 size fractions at a traffic site in Swansea, UK, using
      an Electrical Low Pressure Impactor (ELPI). The PM physicochemical properties
      (including size, morphology, type, and transition metals) were tested. The
      plasmid scission assay (PSA) was used for OR testing of all particles. The
      ultrafine and fine PM fractions (N28-2399; 28-2399 nm) caused more DNA damage
      than coarse PM (N2400-10,000), and the increased capacity of the smaller
      particles to exhibit enhanced (OR) was statistically significant (p<0.05). The
      most bioreactive fraction of PM was N94-155 with a toxic dose (TD50; mass dose
      capable of generating 50% plasmid DNA damage) of 69 MUg/ml. The mean TD35 was
      lower for PM than CB particles, indicating enhanced OR for PM. A difference
      between CB and PM in this study was the higher transition metal content of PM. Zn
      was the most abundant transition metal (by weight) in the ultrafine-fine PM
      fractions, and Fe in the fine-coarse PM. Through this comparison, part of the
      observed increased PM OR was attributed to Zn (and Fe). In this study PM-derived
      DNA damage was dependent upon; 1) particle size, 2) surface area, and 2)
      transition metals. This study supports the view that ROS formation by PM10 is
      related to physicochemistry using evidence with an increased particle size
      resolution.

PMID- 24747251
TI  - Effect of eco-remediation using planted floating bed system on nutrients and
      heavy metals in urban river water and sediment: a field study in China.
AB  - To investigate the effect of the eco-remediation on nutrients and heavy metals in
      river water and sediment, a field study was carried out in a site of a 2-year eco
      remediation mainly using planted floating bed system in an urban river in China.
      Before remediation, the tested properties of water and sediment in the will-be
      remediated area were not different from the control area, except higher
      concentrations of chemical oxygen demand (COD) and total nitrogen (TN) in the
      river water. After remediation, the remediation area showed effective removal of
      in-stream nutrients and elevation of dissolved oxygen and transparency. Compared
      to the control area, the remediation area had higher concentration of nitrate and
      lower concentrations of COD, ammonium, Mn and hexavalent Cr in the river water
      after a 2-year remediation. The remediation area also showed higher
      concentrations of organic carbon, TN, nitrate, sulfate, Fe, Cu, Pb and Zn in the
      sediment than in the control area. Accordingly, special attention should be paid
      to the ecological risk of heavy metals in sediments and plants in river eco
      remediation projects especially in rivers polluted by heavy metals, although the
      metals were lower than the level of considerable ecological risk in this study. 

PMID- 24747252
TI  - Variations of trace metals in two estuarine environments with contrasting
      pollution histories.
AB  - In the present study, seasonal variations of metal concentrations were examined
      in two oyster species, Crassostrea hongkongensis and Crassostrea sikamea, and in
      seawater from a heavily contaminated estuary and a reference estuary. Strong
      temporal fluctuations of metal concentration were observed in oyster tissues as
      well as in seawater from both estuaries, especially for the contaminated estuary
      and for C. hongkongensis with higher accumulation ability. A closer inter-element
      correlation was observed for Cu, Zn, Cr and Ni in both the dissolved and
      particulate phases from the contaminated site, indicating that these metals
      originated from the same industrial sources. Seasonal variations of metals in
      oysters were not significantly related to their concentrations in seawater, but
      were related to the variations of condition index. Our results showed that the
      seasonal patterns of metal concentrations in oysters were largely controlled by
      the biological process, while the variation as well as the concentration were
      dependent on the contamination levels and bioaccumulation ability. 

PMID- 24747253
TI  - Natural vegetation restoration is more beneficial to soil surface organic and
      inorganic carbon sequestration than tree plantation on the Loess Plateau of
      China.
AB  - Natural vegetation restoration and tree plantation are the two most important
      measures for ecosystem restoration on the Loess Plateau of China. However, few
      studies have compared the effects of the two contrasting measures on soil organic
      and inorganic carbon (SOC and SIC) sequestration or have further used SOC and SIC
      isotopes to analyze the inherent sequestration mechanism. This study examined a
      pair of neighboring small watersheds with similar topographical and geological
      backgrounds. Since 1954, natural vegetation restoration has been conducted in one
      of these watersheds, and tree plantation has been conducted in the other. The two
      watersheds have now formed completely different landscapes (naturally restored
      grassland and artificial forestland). Differences in soil bulk density, SOC and
      SIC content and storage, and SOC and SIC delta(13)C values were investigated in
      the two ecosystems in the upper 1m of the soil. We found that SOC storage was
      higher in the grassland than in the forestland, with a difference of 14.90 Mg ha(
      1). The vertical changes in the delta(13)CSOC value demonstrated that the two
      ecosystems have different mechanisms of soil surface organic carbon accumulation.
      The SIC storage in the grassland was lower than that in the forestland, with a
      difference of 38.99 Mg ha(-1). The delta(13)CSIC values indicated that the
      grassland generates more secondary carbonate than the forestland and that SIC was
      most likely transported to the rivers from the grassland as dissolved inorganic
      carbon (DIC). The biogeochemical characteristics of the grassland were favorable
      for the formation of bicarbonate. Thus, more DIC derived from the dissolution of
      root and microbial respired CO2 into soil water could have been transported to
      the rivers through flood runoff. It is necessary to study further the
      transportation of DIC from the grassland because this process can produce a large
      potential carbon sink.

PMID- 24747254
TI  - A comparison of the efficacy and ecosystem impact of residual-based and topsoil
      based amendments for restoring historic mine tailings in the Tri-State mining
      district.
AB  - A long-term research and demonstration site was established on Pb and Zn mine
      wastes in southwestern Missouri in 1999. Municipal biosolids and lime and
      composts were mixed into the wastes at different loading rates. The site was
      monitored intensively after establishment and again in 2012. A site restored with
      topsoil was also included in the 2012 sampling. Initial results including plant,
      earthworm and small mammal assays indicate that the bioaccessibility of metals
      had been significantly reduced as a result of amendment addition. The recent
      sampling showed that at higher loading rates, the residual mixtures have
      maintained a vegetative cover and are similar to the topsoil treatment based on
      nutrient availability and cycling and soil physical properties including bulk
      density and water holding capacity. The ecosystem implications of restoration
      with residuals versus mined topsoil were evaluated. Harvesting topsoil from
      nearby farms would require 1875 years to replace based on natural rates of soil
      formation. In contrast, diverting biosolids from combustion facilities (60% of
      biosolids generated in Missouri are incinerated) would result in greenhouse gas
      savings of close to 400 Mg CO2 per ha.

PMID- 24747255
TI  - Pesticide residues in honeybees, honey and bee pollen by LC-MS/MS screening:
      reported death incidents in honeybees.
AB  - The aim of this study was to investigate reported cases of honeybee death
      incidents with regard to the potential interrelation to the exposure to
      pesticides. Thus honeybee, bee pollen and honey samples from different areas of
      Greece were analyzed for the presence of pesticide residues. In this context an
      LC-ESI-MS/MS multiresidue method of total 115 analytes of different chemical
      classes such as neonicotinoids, organophosphates, triazoles, carbamates,
      dicarboximides and dinitroanilines in honeybee bodies, honey and bee pollen was
      developed and validated. The method presents good linearity over the ranges
      assayed with correlation coefficient values r(2)>=0.99, recoveries ranging for
      all matrices from 59 to 117% and precision (RSD%) values ranging from 4 to 27%.
      LOD and LOQ values ranged - for honeybees, honey and bee pollen - from 0.03 to
      23.3 ng/g matrix weight and 0.1 up to 78 ng/g matrix weight, respectively.
      Therefore this method is sufficient to act as a monitoring tool for the
      determination of pesticide residues in cases of suspected honeybee poisoning
      incidents. From the analysis of the samples the presence of 14 active substances
      was observed in all matrices with concentrations ranging for honeybees from 0.3
      to 81.5 ng/g, for bee pollen from 6.1 to 1273 ng/g and for honey one sample was
      positive to carbendazim at 1.6 ng/g. The latter confirmed the presence of such
      type of compounds in honeybee body and apicultural products.

PMID- 24747256
TI  - Water quality laboratories in Colombia: a GIS-based study of urban and rural
      accessibility.
AB  - The objective of this study was to quantify sample transportation times
      associated with mandated microbiological monitoring of drinking-water in
      Colombia. World Health Organization Guidelines for Drinking-Water Quality
      recommend that samples spend no more than 6h between collection and analysis in a
      laboratory. Census data were used to estimate the minimum number of operational
      and surveillance samples required from piped water supplies under national
      regulations. Drive-times were then computed from each supply system to the
      nearest accredited laboratory and translated into sample holding times based on
      likely daily monitoring patterns. Of 62,502 surveillance samples required
      annually, 5694 (9.1%) were found to be more than 6 h from the nearest of 278
      accredited laboratories. 612 samples (1.0%) were more than 24 hours' drive from
      the nearest accredited laboratory, the maximum sample holding time recommended by
      the World Health Organization. An estimated 30% of required rural samples would
      have to be stored for more than 6 h before reaching a laboratory. The analysis
      demonstrates the difficulty of undertaking microbiological monitoring in rural
      areas and small towns from a fixed laboratory network. Our GIS-based approach
      could be adapted to optimise monitoring strategies and support planning of
      testing and transportation infra-structure development. It could also be used to
      estimate sample transport and holding times in other countries.

PMID- 24747257
TI  - Spatial and temporal variability of surface water pollution in the Mekong Delta,
      Vietnam.
AB  - Surface water pollution in the Vietnamese Mekong Delta (MD) could threaten human,
      animal and ecosystem health given the fact that this water source is intensively
      used for drinking, irrigation and domestic services. We therefore determined the
      levels of pollution by organic pollutants, salts, metals and microbial indicators
      by (bi)monthly monitoring of canals between November 2011 and July 2012 at 32
      sampling locations, representing fresh and saline/brackish environments. The
      results were compared with national water quality guidelines, between the studied
      regions and with water quality data from main waterways. Key factors explaining
      the observed levels of pollution in surface water were identified through
      principal component analysis (PCA). Temporal variations due to tidal regime and
      seasonality were also assessed. Based on regression models, the spatial
      variability of five water quality parameters was visualized using GIS based maps.
      Results indicate that pH (max. 8.6), turbidity (max. 461 FTU), maximum
      concentrations of ammonium (14.7 mg L(-1)), arsenic (44.1 MUg L(-1)), barium
      (157.5 MUg L(-1)), chromium (84.7 MUg L(-1)), mercury (45.5 MUg L(-1)), manganese
      (1659.7 MUg L(-1)), aluminum (14.5 mg L(-1)), iron (17.0 mg L(-1)) and the number
      of Escherichia coli (87,000 CFU 100 mL(-1)) and total coliforms (2,500,000 CFU
      100 mL(-1)) in canals exceed the thresholds set by Vietnamese quality guidelines
      for drinking and domestic purposes. The PCA showed that i) urbanization; ii)
      metal leaching from soils; iii) aquaculture; and iv) tidal regime explain 85% of
      the variance of surface water quality attributes. Significant differences in
      water quality were found due to daily tidal regime and as a result of
      seasonality. Surface water quality maps for dissolved oxygen, ammonium, ortho
      phosphate, manganese and total coliforms were developed to highlight hot-spot
      areas of pollution. The results of this study can assist policy makers in
      developing water management strategies and drinking water companies in selecting
      optimum water extraction locations.

PMID- 24747258
TI  - The impact of major earthquakes and subsequent sewage discharges on the microbial
      quality of water and sediments in an urban river.
AB  - A series of large earthquakes struck the city of Christchurch, New Zealand in
      2010-2011. Major damage sustained by the sewerage infrastructure required direct
      discharge of up to 38,000 m(3)/day of raw sewage into the Avon River of
      Christchurch for approximately six months. This allowed evaluation of the
      relationship between concentrations of indicator microorganisms (Escherichia
      coli, Clostridium perfringens and F-RNA phage) and pathogens (Campylobacter,
      Giardia and Cryptosporidium) in recreational water and sediment both during and
      post-cessation of sewage discharges. Giardia was the pathogen found most
      frequently in river water and sediment, although Campylobacter was found at
      higher levels in water samples. E. coli levels in water above 550 CFU/100 mL were
      associated with increased likelihood of detection of Campylobacter, Giardia and
      Cryptosporidium, supporting the use of E. coli as a reliable indicator for public
      health risk. The strength of the correlation of microbial indicators with
      pathogen detection in water decreased in the following order: E. coli>F-RNA
      phage>C. perfringens. All the microorganisms assayed in this study could be
      recovered from sediments. C. perfringens was observed to accumulate in sediments,
      which may have confounded its usefulness as an indicator of fresh sewage
      discharge. F-RNA phage, however, did not appear to accumulate in sediment and in
      conjunction with E. coli, may have potential as an indicator of recent human
      sewage discharge in freshwater. There is evidence to support the low-level
      persistence of Cryptosporidium and Giardia, but not Campylobacter, in river
      sediments after cessation of sewage discharges. In the event of disturbances of
      the sediment, it is highly probable that there could be re-mobilisation of
      microorganisms beyond the sediment-water exchange processes occurring under base
      flow conditions. Re-suspension events do, therefore, increase the potential risk
      to human health for those who participate in recreational and work-related
      activities in the river environment.

PMID- 24747259
TI  - Chemistry and isotopic composition of precipitation and surface waters in Khumbu
      valley (Nepal Himalaya): N dynamics of high elevation basins.
AB  - We monitored the chemical and isotopic compositions of wet depositions, at the
      Pyramid International Laboratory (5050 ma.s.l.), and surrounding surface waters,
      in the Khumbu basin, to understand precipitation chemistry and to obtain insights
      regarding ecosystem responses to atmospheric inputs. The major cations in the
      precipitation were NH4(+) and Ca(2+), whereas the main anion was HCO3(-), which
      constituted approximately 69% of the anions, followed by NO3(-), SO4(2-) and Cl(
      ). Data analysis suggested that Na(+), Cl(-) and K(+) were derived from the long
      range transport of marine aerosols. Ca(2+), Mg(2+) and HCO3(-) were related to
      rock and soil dust contributions and the NO3(-) and SO4(2-) concentrations were
      derived from anthropogenic sources. Furthermore, NH4(+) was derived from gaseous
      NH3 scavenging. The isotopic composition of weekly precipitation ranged from -1.9
      to -23.20/00 in delta(18)O, and from -0.8 to -1740/00 in delta(2)H, with depleted
      values characterizing the central part of the monsoon period. The chemical
      composition of the stream water was dominated by calcite and/or gypsum
      dissolution. However, the isotopic composition of the stream water did not fully
      reflect the composition of the monsoon precipitation, which suggested that other
      water sources contributed to the stream flow. Precipitation contents for all ions
      were the lowest ones among those measured in high elevation sites around the
      world. During the monsoon periods the depositions were not substantially
      influenced by anthropogenic inputs, while in pre- and post-monsoon seasons the
      Himalayas could not represent an effective barrier for airborne pollution. In the
      late monsoon phase, the increase of ionic contents in precipitation could also be
      due to a change in the moisture source. The calculated atmospheric N load (0.30
      kg ha(-1) y(-1)) was considerably lower than the levels that were measured in
      other high-altitude environments. Nevertheless, the NO3(-) concentrations in the
      surface waters (from 2 to 17 MUeq L(-1)) were greater than expected based on the
      low N inputs from wet deposition.

PMID- 24747260
TI  - Differences in counter-movement jump between boys with and without intellectual
      disability.
AB  - The purpose of this study was to describe the performance and biomechanical
      parameters of the counter-movement jump for young people with ID, in comparison
      with age matched individuals without ID. Volunteers with ID (n=13; age=15.3 +/-
      1.6 years; Wisk III intelligence quotient 55.6 +/- 11.2) and without ID (n=13;
      age=15.4 +/- 1.2 years) performed maximal counter-movement jumps, while knee
      kinematics, vertical ground reaction forces and electromyographic activity of the
      vastus lateralis and biceps femoris were captured. Individuals without ID jumped
      higher than their counterparts with ID and had lower take-off velocity, lower
      knee joint power and stiffness, lower knee joint extension angle and angular
      velocity, longer braking and propulsion phase, lower agonist and higher
      antagonist EMG activity. These results give an insight on possible causes for the
      performance deficit in CMJ in persons with ID and give the potential for such
      individuals to improve their ability to jump higher and more efficiently.

PMID- 24747261
TI  - Effect of fatigue loading on structure and functional behaviour of fascicles from
      energy-storing tendons.
AB  - Tendons can broadly be categorized according to their function: those that act
      purely to position the limb and those that have an additional function as energy
      stores. Energy-storing tendons undergo many cycles of large deformations during
      locomotion, and so must be able to extend and recoil efficiently, rapidly and
      repeatedly. Our previous work has shown rotation in response to applied strain in
      fascicles from energy-storing tendons, indicating the presence of helical
      substructures which may provide greater elasticity and recovery. In the current
      study, we assessed how preconditioning and fatigue loading affect the ability of
      fascicles from the energy-storing equine superficial digital flexor tendon to
      extend and recoil. We hypothesized that preconditioned samples would exhibit
      changes in microstructural strain response, but would retain their ability to
      recover. We further hypothesized that fatigue loading would result in sample
      damage, causing further alterations in extension mechanisms and a significant
      reduction in sample recovery. The results broadly support these hypotheses:
      preconditioned samples showed some alterations in microstructural strain
      response, but were able to recover following the removal of load. However,
      fatigue loaded samples showed visual evidence of damage and exhibited further
      alterations in extension mechanisms, characterized by decreased rotation in
      response to applied strain. This was accompanied by increased hysteresis and
      decreased recovery. These results suggest that fatigue loading results in a
      compromised helix substructure, reducing the ability of energy-storing tendons to
      recoil. A decreased ability to recoil may lead to an impaired response to further
      loading, potentially increasing the likelihood of injury. 

PMID- 24747263
TI  - Proper exercise decreases plasma carcinoembryonic antigen levels with the
      improvement of body condition in elderly women.
AB  - Aging increases the risk of chronic diseases including cancers. Physical exercise
      has the beneficial effects for the elderly susceptible to the development of
      cancers, through maintaining a healthy body condition and improving the immune
      system. However, excessive or insufficient exercise might increase the risk for
      cancer. In the present study, we investigated what exercise frequency improves
      cancer-related biomarkers, such as carcinoembryonic antigen (CEA), alpha
      fetoprotein (AFP), red blood cell (RBC), and white blood cell (WBC), and the body
      composition of elderly women. Fifty-four females, aged 70 to 77 years, were
      divided into 4 groups: control, 1-day exercise (1E), 2-3-day exercise (2-3E), and
      5-day exercise (5E) groups. The control group did not participate in any physical
      activity, while the subjects in the exercise groups underwent the exercise
      program for 12 weeks. As results, CEA was significantly decreased in the exercise
      groups, with the lowest values in 2-3E group. In contrast, AFP, RBC and WBC were
      not significantly changed. CEA is an oncofetal glycoprotein that is overexpressed
      in adenocarcinomas. Although the function of CEA has not been fully understood,
      CEA has been suggested to be involved in the release of pro-inflammatory
      cytokines via stimulating monocytes and macrophages. Moreover, body weight and
      body mass index were improved in the exercise groups, with the lowest levels in
      5E group. Thus, we suggest that exercise for 2-3 days per week decreases the
      expression of CEA and improves body condition, without loading fatigue or stress,
      which may contribute to preventing cancer in the elderly women. 

PMID- 24747262
TI  - Body mass index and mortality in Korean intensive care units: a prospective
      multicenter cohort study.
AB  - BACKGROUND: The level of body mass index (BMI) that is associated with the lowest
      mortality in critically ill patients in Asian populations is uncertain. We aimed
      to examine the association of BMI with hospital mortality in critically ill
      patients in Korea. METHODS: We conducted a prospective multicenter cohort study
      of 3,655 critically ill patients in 22 intensive care units (ICUs) in Korea. BMI
      was categorized into five groups: <18.5, 18.5 to 22.9, 23.0 to 24.9 (the
      reference category), 25.0 to 29.9, and >=30.0 kg/m2. RESULTS: The median BMI was
      22.6 (IQR 20.3 to 25.1). The percentages of patients with BMI<18.5, 18.5 to 22.9,
      23.0 to 24.9, 25.0 to 29.9, and >=30.0 were 12, 42.3, 19.9, 22.4, and 3.3%,
      respectively. The Cox-proportional hazard ratios with exact partial likelihood to
      handle tied failures for hospital mortality comparing the BMI categories <18.5,
      18.5 to 22.9, 25.0 to 29.9, and >=30.0 with the reference category were 1.13
      (0.88 to 1.44), 1.03 (0.84 to 1.26), 0.96 (0.76 to 1.22), and 0.68 (0.43 to
      1.08), respectively, with a highly significant test for trend (p = 0.02).
      CONCLUSIONS: A graded inverse association between BMI and hospital mortality with
      a strong significant trend was found in critically ill patients in Korea.

PMID- 24747264
TI  - A simple and effective method for construction of Escherichia coli strains
      proficient for genome engineering.
AB  - Multiplex genome engineering is a standalone recombineering tool for large-scale
      programming and accelerated evolution of cells. However, this advanced genome
      engineering technique has been limited to use in selected bacterial strains. We
      developed a simple and effective strain-independent method for effective genome
      engineering in Escherichia coli. The method involves introducing a suicide
      plasmid carrying the lambda Red recombination system into the mutS gene. The
      suicide plasmid can be excised from the chromosome via selection in the absence
      of antibiotics, thus allowing transient inactivation of the mismatch repair
      system during genome engineering. In addition, we developed another suicide
      plasmid that enables integration of large DNA fragments into the lacZ genomic
      locus. These features enable this system to be applied in the exploitation of the
      benefits of genome engineering in synthetic biology, as well as the metabolic
      engineering of different strains of E. coli. 

PMID- 24747265
TI  - En plaque spinal leptomeningeal carcinomatosis from metastatic melanoma.

PMID- 24747266
TI  - Spontaneous thoracic epidural hematoma mimicking spinal mass.

PMID- 24747267
TI  - Surgical treatment of a sebaceous cyst in the spine region.

PMID- 24747268
TI  - Giant anterior cervical osteophytes leading to dysphagia in a patient with
      diffuse idiopathic skeletal hyperostosis.

PMID- 24747269
TI  - Electric cell-substrate impedance sensing for the quantification of endothelial
      proliferation, barrier function, and motility.
AB  - Electric Cell-substrate Impedance Sensing (ECIS) is an in vitro impedance
      measuring system to quantify the behavior of cells within adherent cell layers.
      To this end, cells are grown in special culture chambers on top of opposing,
      circular gold electrodes. A constant small alternating current is applied between
      the electrodes and the potential across is measured. The insulating properties of
      the cell membrane create a resistance towards the electrical current flow
      resulting in an increased electrical potential between the electrodes. Measuring
      cellular impedance in this manner allows the automated study of cell attachment,
      growth, morphology, function, and motility. Although the ECIS measurement itself
      is straightforward and easy to learn, the underlying theory is complex and
      selection of the right settings and correct analysis and interpretation of the
      data is not self-evident. Yet, a clear protocol describing the individual steps
      from the experimental design to preparation, realization, and analysis of the
      experiment is not available. In this article the basic measurement principle as
      well as possible applications, experimental considerations, advantages and
      limitations of the ECIS system are discussed. A guide is provided for the study
      of cell attachment, spreading and proliferation; quantification of cell behavior
      in a confluent layer, with regard to barrier function, cell motility, quality of
      cell-cell and cell-substrate adhesions; and quantification of wound healing and
      cellular responses to vasoactive stimuli. Representative results are discussed
      based on human microvascular (MVEC) and human umbilical vein endothelial cells
      (HUVEC), but are applicable to all adherent growing cells. 

PMID- 24747270
TI  - Familiarity breeds dissent: Reliability analyses for British-English idioms on
      measures of familiarity, meaning, literality, and decomposability.
AB  - To date, there have been several attempts made to build a database of normative
      data for English idiomatic expressions (e.g., Libben & Titone, 2008; Titone &
      Connine, 1994), however, there has been some discussion in the literature as to
      the validity and reliability of the data obtained, particularly for
      decomposability ratings. Our work aimed to address these issues by looking at
      ratings from native and non-native speakers and to extend the deeper
      investigation and analysis of decomposability to other aspects of idiomatic
      expressions, namely familiarly, meaning and literality. Poor reliability was
      observed on all types of ratings, suggesting that rather than decomposability
      being a special case, individual variability plays a large role in how
      participants rate idiomatic phrases in general. Ratings from native and non
      native speakers were positively correlated and an analysis of covariance found
      that once familiarity with an idiom was accounted for, most of the differences
      between native and non-native ratings were not significant. Overall, the results
      suggest that individual experience with idioms plays an important role in how
      they are perceived and this should be taken into account when selecting stimuli
      for experimental studies. Furthermore, the results are suggestive of the
      inability of speakers to inhibit the figurative meanings for idioms that they are
      highly familiar with. 

PMID- 24747271
TI  - Statistical atlas construction via weighted functional boxplots.
AB  - Atlas-building from population data is widely used in medical imaging. However,
      the emphasis of atlas-building approaches is typically to estimate a spatial
      alignment to compute a mean/median shape or image based on population data. In
      this work, we focus on the statistical characterization of the population data,
      once spatial alignment has been achieved. We introduce and propose the use of the
      weighted functional boxplot. This allows the generalization of concepts such as
      the median, percentiles, or outliers to spaces where the data objects are
      functions, shapes, or images, and allows spatio-temporal atlas-building based on
      kernel regression. In our experiments, we demonstrate the utility of the approach
      to construct statistical atlases for pediatric upper airways and corpora callosa
      revealing their growth patterns. We also define a score system based on the
      pediatric airway atlas to quantitatively measure the severity of subglottic
      stenosis (SGS) in the airway. This scoring allows the classification of pre- and
      post-surgery SGS subjects and radiographically normal controls. Experimental
      results show the utility of atlas information to assess the effect of airway
      surgery in children. 

PMID- 24747272
TI  - Activating molecules, ions, and solid particles with acoustic cavitation.
AB  - The chemical and physical effects of ultrasound arise not from a direct
      interaction of molecules with sound waves, but rather from the acoustic
      cavitation: the nucleation, growth, and implosive collapse of microbubbles in
      liquids submitted to power ultrasound. The violent implosion of bubbles leads to
      the formation of chemically reactive species and to the emission of light, named
      sonoluminescence. In this manuscript, we describe the techniques allowing study
      of extreme intrabubble conditions and chemical reactivity of acoustic cavitation
      in solutions. The analysis of sonoluminescence spectra of water sparged with
      noble gases provides evidence for nonequilibrium plasma formation. The photons
      and the "hot" particles generated by cavitation bubbles enable to excite the non
      volatile species in solutions increasing their chemical reactivity. For example
      the mechanism of ultrabright sonoluminescence of uranyl ions in acidic solutions
      varies with uranium concentration: sonophotoluminescence dominates in diluted
      solutions, and collisional excitation contributes at higher uranium
      concentration. Secondary sonochemical products may arise from chemically active
      species that are formed inside the bubble, but then diffuse into the liquid phase
      and react with solution precursors to form a variety of products. For instance,
      the sonochemical reduction of Pt(IV) in pure water provides an innovative
      synthetic route for monodispersed nanoparticles of metallic platinum without any
      templates or capping agents. Many studies reveal the advantages of ultrasound to
      activate the divided solids. In general, the mechanical effects of ultrasound
      strongly contribute in heterogeneous systems in addition to chemical effects. In
      particular, the sonolysis of PuO2 powder in pure water yields stable colloids of
      plutonium due to both effects. 

PMID- 24747273
TI  - Stress modulation of hippocampal activity--spotlight on the dentate gyrus.
AB  - The effects of stress on learning and memory are diverse, ranging from impairment
      to facilitation. Many studies emphasize the major role of the hippocampus, mainly
      its CA1 and CA3 areas, in the process of memory formation under emotional and
      stressful conditions. In the current review, we summarize work which suggests
      that the dentate gyrus (DG) of the hippocampus is likely to play a pivotal role
      in defining the impact of stress on hippocampal functioning. We describethe
      effects of stress on long term potentiation (LTP) and local circuit activity in
      the DG and the role of the amygdala in mediating these effects. As one of the
      brain regions known to have a high rate of adult neurogenesis, the effects of
      stress on DG neurogenesis will also be reviewed. Finally, we discuss exposure to
      stress during juvenility and its influence on the adult DG. The DG is a dynamic
      structure which is susceptible to stress. Under stressful conditions, its
      response is variable and complex, much like the behavioral outcomes of such
      circumstances. It is likely to significantly contribute to the diverse effects of
      stress on memory formation. 

PMID- 24747274
TI  - Effects of dietary factors on energy regulation: consideration of multiple-
      versus single-dietary-factor models.
AB  - While short-term studies demonstrate consistent effects of dietary protein,
      fiber, glycemic index and energy density on energy intake, long-term
      effectiveness trials typically indicate small or non-significant effects of these
      dietary factors on long-term weight change. In consequence, most lifestyle
      interventions for weight control typically focus on a single dietary factor, such
      as low energy density, to achieve reductions in energy intake. This paper
      proposes a multiple-dietary-factor model for the effects of dietary factors on
      energy intake and the regulation of energy balance that assumes additive effects
      of different dietary factors. The model is consistent with emerging evidence from
      recent studies examining pairs of dietary factors. Randomized clinical trials are
      now needed to determine whether multiple-dietary-factor prescriptions combined
      with standard behavior modification techniques lead to improved sustainability of
      weight loss in lifestyle interventions compared to conventional single-dietary
      factor prescriptions. 

PMID- 24747275
TI  - Inhalation of coriander volatile oil increased anxiolytic-antidepressant-like
      behaviors and decreased oxidative status in beta-amyloid (1-42) rat model of
      Alzheimer's disease.
AB  - The present study analyzed the possible anxiolytic, antidepressant and
      antioxidant proprieties of inhaled coriander volatile oil extracted from
      Coriandrum sativum var. microcarpum in beta-amyloid (1-42) rat model of
      Alzheimer's disease. The anxiolytic- and antidepressant-like effects of inhaled
      coriander volatile oil were studied by means of in vivo (elevated plus-maze and
      forced swimming tests) approaches. Also, the antioxidant activity in the
      hippocampus was assessed using catalase specific activity and the total content
      of the reduced glutathione. The beta-amyloid (1-42)-treated rats exhibited the
      following: decrease of the locomotor activity, the percentage of the time spent
      and the number of entries in the open arm within elevated plus-maze test and
      decrease of swimming and immobility times within forced swimming test. Exposure
      to coriander volatile oil significantly improved these parameters, suggesting
      anxiolytic- and antidepressant-like effects. Moreover, coriander volatile oil
      decreased catalase activity and increased glutathione level in the hippocampus.
      Our results suggest that multiple exposures to coriander volatile oil can be
      useful as a mean to counteract anxiety, depression and oxidative stress in
      Alzheimer's disease conditions. 

PMID- 24747276
TI  - Comparison of depressive behaviors induced by three stress paradigms in rats.
AB  - Depression is a severe psychiatric disorder, which is a huge burden on both the
      individual and society as a whole. Neurobiological studies of depression on
      humans are limited by ethics. Animal models established by stressor stimulation
      are currently effective tools for the neurobiological study of depression. In
      this study, we comparatively analyzed behavioral heterogeneity, gender, and
      individual differences in animal models reflecting early life stress, adverse
      events in adulthood, or combined early life stress and stressful events in
      adulthood. Results demonstrated that these three different stressors induced
      dissimilar depressive behaviors. Maternal deprivation (MD) induced severe
      anhedonia. Chronic unpredictable stress (CUPS) induced the most severe decrease
      in desperation behavior, moderate anhedonia, and moderate loss of interest in
      exploration of the surroundings. Dural stress (DS) exposure caused the most
      severe decline in interest in exploring the surroundings. Male rats all exhibited
      some form of depressive behavior after they were exposed to MD, CUPS and DS. In
      contrast, no depressive performance was observed in female rats after they were
      exposed to MD, and the CUPS only decreased the total distance the rats crawled in
      the open field test. Rats exhibited more obvious individual differences in
      floating time than in the vertical activity, total distance and sucrose
      preference rate when experiencing stress. Our study suggests that different
      stressors may induce different depression subtypes and that the observed
      differences in the prevalence of depression between genders in the clinic may be
      due to effect of psychosocial factors which affects humans more strongly than
      rats. Our study also suggests that individual difference is more obvious in
      desperation behaviors than that in exploratory interest and anhedonia when the
      individual experienced stress. 

PMID- 24747277
TI  - Exercise patterns, ingestive behaviors, and energy balance.
AB  - Ingestive and exercise behaviors are important determinants of whole body energy
      balance and weight control. An acute bout of exercise generates a transient
      energy deficit, which is only partially compensated for by food intake at the
      next eating occasion or within the next day (loose dietary coupling). Such an
      energy deficit, when repeated chronically, leads to moderate weight loss and
      improved body composition. For this narrative review, we assessed the effects of
      exercise patterns on energy intake, energy balance, and weight control in adults
      primarily using results from randomized acute exercise and chronic training
      studies. The patterns assessed were exercise mode (e.g. resistance, aerobic
      exercise), intensity, duration, time of day, and frequency. The body of evidence
      indicates that exercise training frequency and quantity are influential for
      weight loss. Aerobic training is superior to resistance training for weight loss,
      although resistance training helps preserve lean body mass better. Weight loss
      does not differ among different intensities when energy expenditure is matched by
      adjusting duration. Differing patterns of physical activity exhibited by normal
      weight, overweight, and obese people during weekdays and weekend days are
      consistent with their weight status; leaner people are more physically active.
      Collectively, these findings support acute and chronic exercise patterns as
      important modifiable behaviors to improve energy balance and weight control in
      adults while having minor effects on absolute energy intake. 

PMID- 24747278
TI  - Does the inverted-U function disappear in expert athletes? An analysis of the
      attentional behavior under physical exercise of athletes and non-athletes.
AB  - A number of studies document that physical exercise influences cognitive
      performance in a variety of ways. Some of these studies present the relationship
      between the workload of exercise and the activation level of the central nervous
      system as an inverted-U relationship. Among the factors that could be responsible
      for diverging results are the participants' individual fitness level and the
      athletic status. While athletes and non-athletes do not differ in general
      cognitive skills, athletes are better able to maintain these during physical
      exercise especially under high exercise intensities. Hence, we hypothesized that
      the inverted-U function applies for non-athletes but disappears in team sports
      experts. We compared athletes' and non-athletes' cognitive performance on a
      measure of attentional behavior under three different physical exercise
      intensities. Results showed an increase of non-athletes' attentional breadth
      right up to a certain level of maximal aerobic power before decreasing, as
      expected according to an inverted-U curve. In contrast, athletes' attentional
      breadth continued to increase with higher physical exercise intensities. We
      concluded that physical exercise influences participants' attentional behavior
      and that individual fitness acts as a moderator of this relationship. 

PMID- 24747279
TI  - One dose of oral hexarelin protects chronic cardiac function after myocardial
      infarction.
AB  - Both hexarelin and its natural analog ghrelin exert comparable cardioprotective
      activities. A single dose of ghrelin administered at the very acute phase after
      experimental myocardial infarction positively affects cardiac function in chronic
      heart failure. Therefore, this study aimed to determine whether a single dose of
      oral hexarelin has the same effect in the chronic disease phase. Myocardial
      infarction or sham operation was generated by left coronary artery ligation in
      male C57BL/6J mice, which subsequently received one dose of hexarelin or vehicle
      treatment by oral gavage 30 min after operation. Although the mortality within 14
      days after myocardial infarction did not differ between the groups, hexarelin
      treatment protected cardiac function in the chronic phase as evidenced by higher
      ejection fraction and fractional shortening, as well as lower lung weight/body
      weight and lung weight/tibial length ratios, compared with vehicle treatment.
      Hexarelin treatment concurrently lowered plasma epinephrine and dopamine levels,
      and shifted the balance of autonomic nervous activity toward parasympathetic
      nervous activity as evidenced by a smaller low/high-frequency power ratio and
      larger normalized high-frequency power on heart rate variability analysis. The
      results first demonstrate that one dose of oral hexarelin treatment potentially
      protects chronic cardiac function after acute myocardial infarction, and
      implicate that activating growth hormone secretagogue receptor 1a might be
      beneficial for cardioprotection, although other mechanism may also be involved.

PMID- 24747280
TI  - Changes in urine levels of substance P, vasoactive intestinal peptide and
      calcitonin-gene-related peptide in patients with urinary tract infections.
AB  - Urinary tract infections (UTI) are important health problems and predisposing
      causes of UTI are not entirely known. Neuro-immune interactions play an important
      role in human health and disease. Capsaicin-sensitive sensory nerves which in
      nerve bladder extensively regulate immune system through neuropeptides such as
      substance P (SP), calcitonin-gene related peptide (CGRP) and vasoactive
      intestinal peptide (VIP). In addition these neuropeptides also have anti
      bacterial effects. To determine how the levels of these peptides changes during
      UTI, 67 patients (50-90 years-old) diagnosed with UTI in Akdeniz University
      Faculty of Medicine Hospital were compared with 37 healthy people 50 years or
      older as the control group. Additionally, 7 patients with UTI symptoms (dysuria,
      urgency) but with sterile pyuria were also included in the study. Urine samples
      from 15 patients, whose symptoms regressed with control urine cultures being
      sterile, were taken after completion of the treatments. Urine neuropeptide levels
      were determined by ELISA. CGRP levels are significantly higher in patients with
      UTI, but did not associate with pyuria whereas SP and VIP levels were
      significantly lower in patients with sterile pyuria, indicating sensory nerve
      deficiency. Since CGRP exerts immunosuppressive effects, increased levels of the
      peptide may predispose to UTI. Furthermore, the connection between the observed
      sensory nerve deficiency and sterile pyuria warrants further studies. 

PMID- 24747281
TI  - Serum antimicrobial peptides in patients with familial Mediterranean fever.
AB  - Familial Mediterranean fever (FMF) is characterized by recurrent inflammation of
      serosal and synovial membranes. Despite the fact that it is a genetic disease,
      environmental factors, including infections, are shown to be triggering factors
      associated with the precipitation of attacks in FMF. Antimicrobial peptides
      (AMPs) are components of innate immunity which exert antimicrobial activity
      against many microorganisms. Human AMPs; cathelicidin (LL37) and defensins have
      immunomodulatory properties and are involved in the pathogenesis of many
      inflammatory disorders. Hence, we investigated serum AMPs in 23 newly diagnosed
      FMF patients. Blood samples were obtained at baseline, 6 months after initiation
      of colchicine and during an attack. Twenty-four healthy individuals constituted
      the control group. The concentrations of LL37, alpha-1, beta-1 and beta-2
      defensins were determined by ELISA. Serum AMPs did not change during attacks and
      did not correlate with acute phase reactants. However, serum LL37 and defensins
      were found to be remarkably higher in FMF patients compared to healthy
      individuals both at baseline and 6 months after initiation of colchicine therapy
      which suggest that AMPs might have a role in the pathogenesis of FMF. 

PMID- 24747282
TI  - Plasma levels of adrenomedullin in patients with traumatic brain injury:
      potential contribution to prognosis.
AB  - High plasma levels of adrenomedullin have been associated with stroke severity
      and clinical outcomes. This study aimed to analyze plasma levels of
      adrenomedullin in traumatic brain injury and their association with prognosis.
      One hundred and forty-eight acute severe traumatic brain injury and 148 sex- and
      age-matched healthy controls were recruited in this study. Plasma adrenomedullin
      concentration was measured by enzyme-linked immunosorbent assay. Unfavorable
      outcome was defined as Glasgow Outcome Scale score of 1-3. Compared to controls,
      the patients had significantly higher plasma concentrations of adrenomedullin,
      which were also highly associated negatively with Glasgow Coma Scale score.
      Plasma adrenomedullin level was proved to be an independent predictor for 6-month
      mortality and unfavorable outcome of patients in a multivariate analysis. A
      receiver operating characteristic curve was configured to show that a baseline
      plasma adrenomedullin level predicted 6-month mortality and unfavorable outcome
      of patients with high area under curve. The predictive performance of the plasma
      adrenomedullin concentration was also similar to that of Glasgow Coma Scale score
      for the prediction of 6-month mortality and unfavorable outcome of patients. In a
      combined logistic-regression model, adrenomedullin improved the area under curve
      of Glasgow Coma Scale score for the prediction of 6-month mortality and
      unfavorable outcome of patients, but the differences did not appear to be
      statistically significant. Thus, high plasma levels of adrenomedullin are
      associated with head trauma severity, and may independently predict long-term
      clinical outcomes of traumatic brain injury. 

PMID- 24747283
TI  - Decreased saliva/serum irisin concentrations in the acute myocardial infarction
      promising for being a new candidate biomarker for diagnosis of this pathology.
AB  - Irisin is a muscle-secreted protein. Cardiac muscle produces more irisin than
      skeletal muscle in response to acute exercise, and is associated with myocardial
      infarction (MI) in an experimental model induced by isoproterenol in rats. The
      timing and significance of its release in patients with acute myocardial
      infarction (AMI) needs further investigation. We have studied the relationship
      between serum/saliva irisin concentration and AMI in humans. Serum and saliva
      samples were taken within 3 days of admission in 11 patients with AMI and in 14
      matched controls. Salivary gland irisin was detected immunohistochemically, and
      serum and saliva levels were measured by ELISA. The three major paired salivary
      glands (submandibular, sublingual and parotid) produce and release irisin into
      saliva. Troponin-I, CK, CK-MB concentrations in the AMI group gradually increased
      from up to 12h, while saliva and serum irisin gradually decreased from up to 48
      h, compared with the control group (P<0.05). After 12h, troponin-I, CK, CK-MB
      started to decrease, while saliva and serum irisin started to increase at 72 h.
      Serum irisin levels correlated with age, while troponin I, CK-MB, and CK were
      correlated and with saliva irisin in AMI patients. Besides cardiac troponin and
      CK-MB, irisin adds new diagnostic information in AMI patients, and the gradual
      decrease of saliva/serum irisin over 48 h could be a useful biomarker.

PMID- 24747285
TI  - The Impact of Personal Metaphors and Memorable Interpersonal Communication on
      Body Satisfaction.
AB  - Memorable messages about body size can have profound negative psychological and
      emotional effects on body image and personal health. We found that both men and
      women recalled more negative than positive memorable messages about their body
      appearance and size. Participants who reported receiving negative memorable
      messages also revealed stronger current body dissatisfaction and poorer self
      image than participants who reported positive memorable messages. Participants
      who received negative body comments also described their own body using negative
      metaphors. Negative memorable messages often occurred in front of third parties
      who expressed approval for the message, sometimes in the form of laughter. We
      discuss the mental health consequences of negative messages about body size and
      the implications for public health campaigns.

PMID- 24747284
TI  - Opportunities for merging chemical and biological synthesis.
AB  - Organic chemists and metabolic engineers use largely orthogonal technologies to
      access small molecules like pharmaceuticals and commodity chemicals. As the use
      of biological catalysts and engineered organisms for chemical production grows,
      it is becoming increasingly evident that future efforts for chemical manufacture
      will benefit from the integration and unified expansion of these two fields. This
      review will discuss approaches that combine chemical and biological synthesis for
      small molecule production. We highlight recent advances in combining enzymatic
      and non-enzymatic catalysis in vitro, discuss the application of design
      principles from organic chemistry for engineering non-biological reactivity into
      enzymes, and describe the development of biocompatible chemistry that can be
      interfaced with microbial metabolism. 

PMID- 24747286
TI  - The Genetic Testing Experience of BRCA-Positive Women: Deciding Between
      Surveillance and Surgery.
AB  - Little is known about how the breast cancer (BRCA) gene mutation affects women's
      decision-making processes. I use a feminist standpoint lens to explore the
      process by which BRCA-positive women came to socially construct and understand
      their risk for developing breast and/or ovarian cancer and the treatment options
      they elected post-testing. This study included in-depth interviews with 64 BRCA
      positive mutation women, some of whom sought surveillance and others who opted
      for preventive surgical intervention. The in-depth analysis and case study
      approach revealed a complex cancer risk assessment resulting in a "nexus of
      decision making" that does not mirror a statistical medical model of risk
      assessment. The particular configuration of women's nexus of decision making
      impacted their pre- and posttesting BRCA experience as empowering or
      disempowering, regardless of whether they elected surgery or surveillance. I
      discuss the implications for development of clinical strategies that will serve
      to enhance women's pre- and post-BRCA decision making.

PMID- 24747287
TI  - Perilous Uncertainty: Situating Women's Breast-Health Seeking in Northern Peru.
AB  - Breast cancer rates in Peru, as in other low- and middle-income countries,
      continue to rise, and survival rates are poor, in part because many women are
      diagnosed with late-stage disease. As part of a pilot project to improve breast
      cancer screening and diagnostic services in remote regions of Peru, the Program
      for Appropriate Technology in Health (PATH) partnered with Peruvian organizations
      to train community health workers in breast health promotion and providers in
      clinical breast exam (CBE). To inform these strategies, we undertook a
      qualitative study to determine factors that influence Peruvian women's decisions
      to seek CBE. Anthropological approaches incorporating the PRECEDE/PROCEED public
      health model guided our conversations with providers and women living in the
      region of the pilot intervention. Grounded theory analysis helped us uncover a
      central theme of uncertainty, a state of doubt and insecurity that created a
      sense of impotent worry and impeded clinical health-seeking behaviors.

PMID- 24747288
TI  - Prospective therapeutic agents for obesity: molecular modification approaches of
      centrally and peripherally acting selective cannabinoid 1 receptor antagonists.
AB  - Presently, obesity is one of the major health problems in the developed as well
      as developing countries due to lack of physical work and increasing sedentary
      life style. Endocannabinoid system (ECS) and especially cannabinoid 1 (CB1)
      receptor play a key role in energy homeostasis. Food intake and energy storage is
      enhanced due to the stimulation of ECS hence, inhibition of ECS by blocking CB1
      receptors could be a promising approach in the treatment of obesity. Rimonabant,
      a diaryl pyrazole was the first potent and selective CB1 receptor antagonist that
      was introduced into the market in 2006 but was withdrawn in 2008 due to its
      psychiatric side effects. Researchers all over the world are interested to
      develop peripherally acting potent and selective CB1 receptor antagonists having
      a better pharmacokinetic profile and therapeutic index. In this development
      process, pyrazole ring of rimonabant has been replaced by different bioisosteric
      scaffolds like pyrrole, imidazole, triazole, pyrazoline, pyridine etc. Variations
      in substituents around the pyrazole ring have also been done. New strategies were
      also employed for minimizing the psychiatric side effects by making more polar
      and less lipophilic antagonists/inverse agonists along with neutral antagonists
      acting peripherally. It has been observed that some of the peripherally acting
      compounds do not show adverse effects and could be used as potential leads for
      the further design of selective CB1 receptor antagonists. Chemical modification
      strategies used for the development of selective CB1 receptor antagonists are
      discussed here in this review. 

PMID- 24747289
TI  - Discovery, synthesis, and structure-activity relationships of 20(S)
      protopanaxadiol (PPD) derivatives as a novel class of AMPKalpha2beta1gamma1
      activators.
AB  - Adenosine 5'-monophosphate-activated protein kinase (AMPK) has been demonstrated
      as a promising drug target due to its regulatory function in glucose and lipid
      metabolism. 20(S)-protopanoxadiol (PPD) was firstly identified from high
      throughput screening as a small molecule activator of AMPK subtype
      alpha2beta1gamma1. In order to enhance its potency on AMPK, a series of PPD
      derivatives were synthesized and evaluated. Structure-activity relationship study
      showed that the amine derivatives at the 24-position (groups I-VI) can improve
      the potency (EC50: 0.7-2.3 MUM) and efficacy (fold: 2.5-3.8). Among them,
      compounds 12 and 13 exhibited the best potency (EC50: 1.2 and 0.7 MUM) and
      efficacy (fold: 3.7 and 3.8). Further study suggested the mechanism of AMPK
      activation may functioned at the allosteric position, resulting the inhibition of
      the lipid synthesis in HepG2 cell model. 

PMID- 24747290
TI  - Design, economical synthesis and antiplasmodial evaluation of vanillin derived
      allylated chalcones and their marked synergism with artemisinin against
      chloroquine resistant strains of Plasmodium falciparum.
AB  - The in vitro blood stage antiplasmodial activity of a series of allylated
      chalcones based on the licochalcone A as lead molecule was investigated against
      chloroquine (CQ) sensitive Pf3D7 and CQ resistant PfINDO strains of Plasmodium
      falciparum using SYBR Green I assay. Of the forty two chalcones tested, eight
      showed IC50 <= 5 MUM. Structure-activity relationship (SAR) studies revealed 9 {1
      (4-Chlorophenyl)-3-[3-methoxy-4-(prop-2-en-1-yloxy)phenyl]-prop-2-en-1-one} as
      the most potent (IC50: 2.5 MUM) against Pf3D7 with resistance indices of 1.2 and
      6.6 against PfDd2 and PfINDO strains, respectively. Later on, the synergistic
      effects 9 with standard antimalarials {artemisinin (ART) and chloroquine (CQ)}
      were studied in order to provide the basis for the selection of the best partner
      drug. In vitro combinations of 9 with ART showed strong synergy against PfINDO
      (SigmaFIC50: 0.31-0.72) but additive to slight antagonistic effects (SigmaFIC50:
      1.97-2.64) against Pf3D7. SigmaFIC50 0.31 of ART+9 combination corresponded to a
      320 fold and 3 fold reduction in IC50 of 9 and ART, respectively. Similar
      combinations of 9 with CQ showed synergy to additivity to mild antagonism against
      the two strains {SigmaFIC50: 0.668-2.269 (PfINDO); 1.45-2.83 (Pf3D7)}. Drug
      exposure followed by drug withdrawal indicated that 9 taken alone at IC100 killed
      rings, trophozoites and schizonts of P. falciparum. The combination of ART and 9
      (1X SigmaFIC100) selectively inhibited the growth of rings while the 2X
      SigmaFIC100 combination of the same caused killing of rings without affecting
      trophozoites and schizonts. In contrast, the 1X combination of CQ and 9
      (SigmaFIC100: 0.5) killed rings and trophozoites. DNA fragmentation and loss of
      mitochondrial membrane potential (DeltaPsim) in the 9 treated P. falciparum
      culture indicated apoptotic death in malaria parasites. Prediction of ADME
      properties revealed that most of the molecules did not violate Lipinski's
      parameters and have low TPSA value suggesting good absorption. The results
      suggest the promising drug-like properties of 9 against CQ resistant Pf and
      propensity for synergy with classical antimalarial drugs together with easy and
      economical synthesis. 

PMID- 24747291
TI  - The electrical coupling and the hippocampal formation theta rhythm in rats.
AB  - Gap junctions (GJs) were discovered more than five decades ago, and since that
      time enormous strides have been made in understanding their structure and
      function. Despite the voluminous literature concerning the function of GJs, the
      involvement of these membrane structures in the central mechanisms underlying
      oscillations and synchrony in the neuronal network is still a matter of intensive
      debate. This review summarizes what is known concerning the involvement of GJs as
      electrical synapses in mechanisms underlying the generation of theta band
      oscillations. The first part of the chapter discusses the role of GJs in
      mechanisms of oscillations and synchrony. Following this, in vitro, ex vivo, and
      in vivo experiments concerning the involvement of GJs in the generation of
      hippocampal formation theta in rats are reviewed. 

PMID- 24747292
TI  - Brassinin and its derivatives as potential anticancer agents.
AB  - The aim of the study was to investigate the anti-proliferative activity of
      brassinin and its derivatives on human cancer cell lines. We found that among
      twenty-one tested compounds, 1- methoxybrassinin exerted the most potent anti
      proliferative activity in Caco-2 cells with IC50 8.2 (+/-1.2)MUmoll(-1). The flow
      cytometric analysis revealed a 1-methoxybrassinin-induced increase in the sub-G1
      DNA content fraction which is considered to be a marker of apoptotic cell death.
      Apoptosis was also confirmed by DNA fragmentation assay. Moreover, quantitative
      real-time PCR showed that 1-methoxybrassinin upregulated the expression of pro
      apoptotic Bax and downregulated the expression of anti-apoptotic genes Bcl-2 and
      Bcl-xL. The compound also increased activity of caspase-3, -7, cleaved PARP and
      decreased intracellular GSH content. The present study has assessed the in vitro
      anti-proliferative potential of 1-methoxybrassinin. The results generate a
      rationale for in vivo efficacy studies with this compound in preclinical cancer
      models.

PMID- 24747293
TI  - A robotic BG1Luc reporter assay to detect estrogen receptor agonists.
AB  - Endocrine disrupting chemicals with estrogenic activity (EA) have been associated
      with various adverse health effects. US agencies (ICCVAM/NICEATM) tasked to
      assess in vitro transcription activation assays to detect estrogenic receptor
      (ER) agonists for EA have recently validated a BG1Luc assay in manual format, but
      prefer robotic formats. We have developed a robotic BG1Luc EA assay to detect EA
      that demonstrated 100% concordance with ICCVAM meta-analyses and ICCVAM BG1Luc
      results in manual format for 27 ICCVAM test substances, i.e. no false negatives
      or false positives. This robotic assay also consistently assessed other, more
      problematic ICCVAM test substances such as clomiphene citrate, L-thyroxin, and
      tamoxifen. Agonist responses using this robotic BG1Luc assay were consistently
      inhibited by the ER antagonist ICI 182,780, confirming that agonist responses
      were due to binding to ERs rather than to a non-specific agonist response. This
      robotic assay also detected EA in complex mixtures of substances such as extracts
      of personal care products, plastic resins or plastic consumer products. This
      robotic BG1Luc assay had at least as high accuracy and greater sensitivity and
      repeatability when compared to its manual version or to the other ICCVAM/OECD
      validated assays for EA (manual BG1Luc and CERI).

PMID- 24747294
TI  - Cytotoxicity and immunotoxicity of cyclopiazonic acid on human cells.
AB  - In this study, in vitro cytotoxicity and immunotoxicity of the mycotoxin
      cyclopiazonic acid (CPA) was evaluated on human cells. To evaluate cytoxicity,
      several cellular targets were used (CD34+, monocytes, THP-1 and Caco-2).
      Monocytes were more sensitive to CPA than the THP-1 monocytic cell line after 48h
      of incubation in the tested conditions. Half maximal inhibitory concentration
      (IC50) were determined to be 8.5 * 10(-8) and 1.75 * 10(-7)M for monocytes and
      THP1, respectively, while IC50>1.25 * 10(-7)M was observed for Caco-2 and CD34+
      cells. The CPA effect on macrophage differentiation was also examined at non
      cytotoxic concentrations. The monocyte differentiation process was markedly
      disturbed in the presence of CPA. After 6 days of culture, CD71 expression was
      downregulated, while CD14 and CD11a expressions did not change. Moreover,
      activated macrophages showed a raised burst activity and TNF-alpha secretion.
      Overall, the results indicated that CPA exhibited toxicity on various human
      cellular models. Moreover, at non-cytotoxic concentrations, CPA disturbed human
      monocytes differentiation into macrophages. This work contributes to
      understanding the immunosuppressive properties of this food-related toxin.

PMID- 24747295
TI  - Toxicity of the herbicide linuron as assessed by bacterial and mitochondrial
      model systems.
AB  - Linuron is one of the most intensively used herbicides with predictable effects
      on the environment and non-target organisms. In the present study, two in vitro
      biological models (a Bacillus sp. and rat liver mitochondria) were used to
      evaluate linuron toxicity at a cell/subcellular level. Linuron inhibited
      bacterial growth and NADH-supported respiration, similar IC50 values being
      estimated for both toxic responses (74 and 98 MUM, respectively). At
      concentrations up to 120 MUM, linuron perturbed the respiration and
      phosphorylation efficiency of rat liver mitochondria, reflected by an increase of
      state 4 respiration and a decrease of the transmembrane potential, state 3 and
      FCCP-uncoupled respiration, when malate/glutamate or succinate were used as
      respiratory substrates. Consequently, a decrease of the respiratory control and
      ADP/O ratio was observed. This study suggests that linuron membrane interactions
      with adverse repercussions in the activity of membrane enzymatic complexes, such
      as those which constitute the prokaryotic and mitochondrial respiratory systems,
      may underlie the toxic effects exerted by that herbicide on non-target organisms.
      Moreover, this work contributes to the establishment of our bacterial model
      system as a good tool for chemical toxicity screening.

PMID- 24747296
TI  - RyR2 modulates a Ca2+-activated K+ current in mouse cardiac myocytes.
AB  - In cardiomyocytes, Ca2+ entry through voltage-dependent Ca2+ channels (VDCCs)
      binds to and activates RyR2 channels, resulting in subsequent Ca2+ release from
      the sarcoplasmic reticulum (SR) and cardiac contraction. Previous research has
      documented the molecular coupling of small-conductance Ca2+-activated K+ channels
      (SK channels) to VDCCs in mouse cardiac muscle. Little is known regarding the
      role of RyRs-sensitive Ca2+ release in the SK channels in cardiac muscle. In this
      study, using whole-cell patch clamp techniques, we observed that a Ca2+-activated
      K+ current (IK,Ca) recorded from isolated adult C57B/L mouse atrial myocytes was
      significantly decreased by ryanodine, an inhibitor of ryanodine receptor type 2
      (RyR2), or by the co-application of ryanodine and thapsigargin, an inhibitor of
      the sarcoplasmic reticulum calcium ATPase (SERCA) (p<0.05, p<0.01, respectively).
      The activation of RyR2 by caffeine increased the IK,Ca in the cardiac cells
      (p<0.05, p<0.01, respectively). We further analyzed the effect of RyR2 knockdown
      on IK,Ca and Ca2+ in isolated adult mouse cardiomyocytes using a whole-cell patch
      clamp technique and confocal imaging. RyR2 knockdown in mouse atrial cells
      transduced with lentivirus-mediated small hairpin interference RNA (shRNA)
      exhibited a significant decrease in IK,Ca (p<0.05) and [Ca2+]i fluorescence
      intensity (p<0.01). An immunoprecipitated complex of SK2 and RyR2 was identified
      in native cardiac tissue by co-immunoprecipitation assays. Our findings indicate
      that RyR2-mediated Ca2+ release is responsible for the activation and modulation
      of SK channels in cardiac myocytes. 

PMID- 24747297
TI  - Repeated nitrogen dioxide exposures and eosinophilic airway inflammation in
      asthmatics: a randomized crossover study.
AB  - BACKGROUND: Nitrogen dioxide (NO2), a ubiquitous atmospheric pollutant, may
      enhance the asthmatic response to allergens through eosinophilic activation in
      the airways. However, the effect of NO2 on inflammation without allergen exposure
      is poorly studied. OBJECTIVES: We investigated whether repeated peaks of NO2, at
      various realistic concentrations, induce changes in airway inflammation in
      asthmatics. METHODS: Nineteen nonsmokers with asthma were exposed at rest in a
      double-blind, crossover study, in randomized order, to 200 ppb NO2, 600 ppb NO2,
      or clean air once for 30 min on day 1 and twice for 30 min on day 2. The three
      series of exposures were separated by 2 weeks. The inflammatory response in
      sputum was measured 6 hr (day 1), 32 hr (day 2), and 48 hr (day 3) after the
      first exposure, and compared with baseline values measured twice 10-30 days
      before the first exposure. RESULTS: Compared with baseline measurements, the
      percentage of eosinophils in sputum increased by 57% after exposure to 600 ppb
      NO2 (p = 0.003) but did not change significantly after exposure to 200 ppb. The
      slope of the association between the percentage of eosinophils and NO2 exposure
      level was significant (p = 0.04). Eosinophil cationic protein in sputum was
      highly correlated with eosinophil count and increased significantly after
      exposure to 600 ppb NO2 (p = 0.001). Lung function, which was assessed daily, was
      not affected by NO2 exposure. CONCLUSIONS: We observed that repeated peak
      exposures of NO2 performed without allergen exposure were associated with airway
      eosinophilic inflammation in asthmatics in a dose-related manner.

PMID- 24747298
TI  - Precooling and percooling (cooling during exercise) both improve performance in
      the heat: a meta-analytical review.
AB  - BACKGROUND: Exercise increases core body temperature (Tc), which is necessary to
      optimise physiological processes. However, excessive increase in Tc may impair
      performance and places participants at risk for the development of heat-related
      illnesses. Cooling is an effective strategy to attenuate the increase in Tc. This
      meta-analysis compares the effects of cooling before (precooling) and during
      exercise (percooling) on performance and physiological outcomes. METHODS: A
      computerised literature search, citation tracking and hand search were performed
      up to May 2013. 28 studies met the inclusion criteria, which were trials that
      examined the effects of cooling strategies on exercise performance in men, while
      exercise was performed in the heat (>30 degrees C). 20 studies used precooling,
      while 8 studies used percooling. RESULTS: The overall effect of precooling and
      percooling interventions on exercise performance was +6.7+/-0.9% (effect size
      (ES)=0.43). We found a comparable effect (p=0.82) of precooling (+5.7+/-1.0%
      (ES=0.44)) and percooling (+9.9+/-1.9% (ES=0.40)) to improve exercise
      performance. A lower finishing Tc was found in precooling (38.9 degrees C)
      compared with control condition (39.1 degrees C, p=0.03), while Tc was comparable
      between conditions in percooling studies. No correlation between Tc and
      performance was found. We found significant differences between cooling
      strategies, with a combination of multiple techniques being most effective for
      precooling (p<0.01) and ice vest for percooling (p=0.02). CONCLUSIONS: Cooling
      can significantly improve exercise performance in the heat. We found a comparable
      ES for precooling and percooling on exercise performance, while the type of
      cooling technique importantly impacts the effects. Precooling lowered the
      finishing core temperature, while there was no correlation between Tc and
      performance.

PMID- 24747300
TI  - Knowledge, attitudes, and practices of nonpharmaceutical interventions following
      school dismissals during the 2009 Influenza A H1N1 pandemic in Michigan, United
      States.
AB  - BACKGROUND: Many schools throughout the United States reported an increase in
      dismissals due to the 2009 influenza A H1N1 pandemic (pH1N1). During the fall
      months of 2009, more than 567 school dismissals were reported from the state of
      Michigan. In December 2009, the Michigan Department of Community Health, in
      collaboration with the United States Centers for Disease Control and Prevention,
      conducted a survey to describe the knowledge, attitudes, and practices (KAPs) of
      households with school-aged children and classroom teachers regarding the
      recommended use of nonpharmaceutical interventions (NPIs) to slow the spread of
      influenza. METHODS: A random sample of eight elementary schools (kindergarten
      through 5th grade) was selected from each of the eight public health preparedness
      regions in the state. Within each selected school, a single classroom was
      randomly identified from each grade (K-5), and household caregivers of the
      classroom students and their respective teachers were asked to participate in the
      survey. RESULTS: In total, 26% (2,188/8,280) of household caregivers and 45%
      (163/360) of teachers from 48 schools (of the 64 sampled) responded to the
      survey. Of the 48 participating schools, 27% (13) experienced a school dismissal
      during the 2009 fall term. Eighty-seven percent (1,806/2,082) of caregivers and
      80% (122/152) of teachers thought that the 2009 influenza A H1N1 pandemic was
      severe, and >90% of both groups indicated that they told their children/students
      to use NPIs, such as washing hands more often and covering coughs with tissues,
      to prevent infection with influenza. CONCLUSIONS: Knowledge and instruction on
      the use of NPIs appeared to be high among household caregivers and teachers
      responding to the survey. Nevertheless, public health officials should continue
      to explain the public health rationale for NPIs to reduce pandemic influenza.
      Ensuring this information is communicated to household caregivers and teachers
      through trusted sources is essential.

PMID- 24747299
TI  - Hematopoietic overexpression of FOG1 does not affect B-cells but reduces the
      number of circulating eosinophils.
AB  - We have identified expression of the gene encoding the transcriptional
      coactivator FOG-1 (Friend of GATA-1; Zfpm1, Zinc finger protein multitype 1) in B
      lymphocytes. We found that FOG-1 expression is directly or indirectly dependent
      on the B cell-specific coactivator OBF-1 and that it is modulated during B cell
      development: expression is observed in early but not in late stages of B cell
      development. To directly test in vivo the role of FOG-1 in B lymphocytes, we
      developed a novel embryonic stem cell recombination system. For this, we combined
      homologous recombination with the FLP recombinase activity to rapidly generate
      embryonic stem cell lines carrying a Cre-inducible transgene at the Rosa26 locus.
      Using this system, we successfully generated transgenic mice where FOG-1 is
      conditionally overexpressed in mature B-cells or in the entire hematopoietic
      system. While overexpression of FOG-1 in B cells did not significantly affect B
      cell development or function, we found that enforced expression of FOG-1
      throughout all hematopoietic lineages led to a reduction in the number of
      circulating eosinophils, confirming and extending to mammals the known function
      of FOG-1 in this lineage. 

PMID- 24747302
TI  - Introduction to the ECR special odontology issue.

PMID- 24747304
TI  - Nuclear phosphoproteome of developing chickpea seedlings (Cicer arietinum L.) and
      protein-kinase interaction network.
AB  - Nucleus, the control centre of eukaryotic cell, houses most of the genetic
      machineries required for gene expression and their regulation. Post translational
      modifications of proteins, particularly phosphorylation control a wide variety of
      cellular processes but its functional connectivity, in plants, is still elusive.
      This study profiled the nuclear phosphoproteome of a grain legume, chickpea, to
      gain better understanding of such event. Intact nuclei were isolated from 3-week
      old seedlings using two independent methods, and nuclear proteins were resolved
      by 2-DE. In a separate set of experiments, phosphoproteins were enriched using
      IMAC method and resolved by 1-DE. The separated proteins were stained with
      phosphospecific Pro-Q Diamond stain. Proteomic analyses led to the identification
      of 107 putative phosphoproteins, of which 86 were non-redundant. Multiple sites
      of phosphorylation were predicted on several key elements, which included both
      regulatory and functional proteins. The analysis revealed an array of
      phosphoproteins, presumably involved in a variety of cellular functions, viz.,
      protein folding (24%), signalling and gene regulation (22%), DNA replication,
      repair and modification (16%), and metabolism (13%), among others. These results
      represent the first nucleus-specific phosphoproteome map of a non-model legume,
      which would provide insights into the possible function of protein
      phosphorylation in plants. BIOLOGICAL SIGNIFICANCE: Chickpea is grown over 10
      million hectares of land worldwide, and global production hovers around 8.5
      million metric tons annually. Despite its nutritional merits, it is often
      referred to as 'orphan' legume and has remained outside the realm of large-scale
      functional genomics studies. While current chickpea genome initiative has
      primarily focused on sequence information and functional annotation, proteomics
      analyses are limited. It is thus important to study the proteome of the cell
      organelle particularly the nucleus, which harbors most of the genetic information
      and gene expression machinery. Phosphorylation-dependent modulation of gene
      expression plays a vital role but the complex networks of phosphorylation are
      poorly understood. This inventory of nuclear phosphoproteins would provide
      valuable insights into the dynamic regulation of cellular phenotype through
      phosphorylation. This article is part of a Special Issue entitled: Proteomics of
      non-model organisms.

PMID- 24747305
TI  - Determination of disulfide linkages in antimicrobial peptides of the macin family
      by combination of top-down and bottom-up proteomics.
AB  - Macins are a distinct class of antimicrobial peptides (AMPs) produced by leeches
      and Hydra. Their function depends strongly on their three-dimensional structure.
      In order to support structural elucidation of these AMPs, the knowledge and
      proper assignment of disulfide bonds formed in these cysteine-rich peptides is a
      prerequisite. In this report, we outline an analytical strategy, encompassing a
      combination of top-down MS based analytics and sequence-dependent enzyme cleavage
      under native conditions followed by high mass accuracy and high resolution MS/MS
      analysis by LTQ-Orbitrap MS to assign disulfide linkages of three members of the
      macin family, namely neuromacin, theromacin, and hydramacin-1. The results
      revealed that the eight cysteine residues conserved in all three macins form the
      same four disulfide bonds, i.e. [C1:C6], [C2:C5], [C3:C7], and [C4:C8].
      Theromacin, which possess two additional cysteine residues, forms a fifth
      disulfide bond. BIOLOGICAL SIGNIFICANCE: Beside the high biological significance
      which is based on the inherent dependence of biological activity on the
      structural features of antimicrobial peptides (which holds true for entirely
      every protein), the presented analytical strategy will be of wide interest, as it
      widens the available toolbox for the analysis of this important posttranslational
      modification.

PMID- 24747303
TI  - Quantitative proteomic analysis of hepatocyte-secreted extracellular vesicles
      reveals candidate markers for liver toxicity.
AB  - Extracellular vesicles have created great interest as possible source of
      biomarkers for different biological processes and diseases. Although the
      biological function of these vesicles is not fully understood, it is clear that
      they participate in the removal of unnecessary cellular material and act as
      carriers of various macromolecules and signals between the cells. In this report,
      we analyzed the proteome of extracellular vesicles secreted by primary
      hepatocytes. We used one- and two-dimensional liquid chromatography combined with
      data-independent mass spectrometry. Employing label-free quantitative proteomics,
      we detected significant changes in vesicle protein expression levels in this in
      vitro model after exposure to well-known liver toxins (galactosamine and
      Escherichia coli-derived lipopolysaccharide). The results allowed us to identify
      candidate markers for liver injury. We validated a number of these markers in
      vivo, providing the basis for the development of novel methods to evaluate drug
      toxicity. This report strongly supports the application of proteomics in the
      study of extracellular vesicles released by well-controlled in vitro cellular
      systems. Analysis of such systems should help to identify specific markers for
      various biological processes and pathological conditions. BIOLOGICAL
      SIGNIFICANCE: Identification of low invasive candidate marker for hepatotoxicity.
      Support to apply proteomics in the study of extracellular vesicles released by
      well-controlled in vitro cellular systems to identify low invasive markers for
      diseases.

PMID- 24747306
TI  - Cord entanglement.

PMID- 24747307
TI  - A neonate with a 'milky' blood. What can it be?

PMID- 24747308
TI  - Anesthesia and cancer recurrence: is the balance of evidence shifting?

PMID- 24747309
TI  - Paravertebral block for analgesia after pediatric thoracic surgery.

PMID- 24747310
TI  - Epidural removal after perioperative myocardial infarction and coronary stent
      placement.

PMID- 24747311
TI  - Fluoroscopically guided epidural catheter placement in a patient with
      osteoporosis pseudoglioma undergoing bilateral femoral osteotomies.

PMID- 24747312
TI  - Defining adductor canal block.

PMID- 24747313
TI  - Reply to Dr Bendtsen.

PMID- 24747314
TI  - Anesthesia for clavicular fracture and surgery.

PMID- 24747315
TI  - Adductor canal block or midthigh saphenous nerve block: same same but different
      name!

PMID- 24747316
TI  - Reply to dr Andersen and Zaric.

PMID- 24747317
TI  - Anesthesia for clavicular fracture: selective supraclavicular nerve block is the
      key.

PMID- 24747318
TI  - Reply to Drs Valdes-Vilches and Sanchez-del Aguila.

PMID- 24747319
TI  - Sonography of the paraneural sheath of the sciatic nerve in the popliteal fossa:
      more than a bifurcation.

PMID- 24747320
TI  - Reply to Drs Wolf and Gray.

PMID- 24747321
TI  - Anesthetic or analgesic effect of N2O in acute pain model?

PMID- 24747322
TI  - The use of anatomical position for regional block description.

PMID- 24747323
TI  - Reply to Drs Weller and Henshaw.

PMID- 24747324
TI  - Systemic local anesthetic toxicity after local infiltration analgesia following a
      polyethylene tibial insert exchange: a case report.

PMID- 24747325
TI  - Regional anesthesia: business class pain management?

PMID- 24747326
TI  - Exposure of fathead minnows to municipal wastewater effluent affects
      intracellular signaling pathways in the liver.
AB  - Municipal wastewater effluent can impact its receiving environment. In the St.
      Lawrence River, male fish living downstream from Montreal exhibit increased
      hepatic vitellogenin, intersex, delayed spermatogenesis and altered immune
      function. Few studies have examined genome-wide effects associated with municipal
      effluent exposure in fish to decipher the mechanisms of toxicity. The present
      objective was to identify hepatic cellular signaling pathways in fathead minnows
      following exposure to municipal wastewater effluent. Immature minnows were
      exposed for 21 days to either 0% (Control) or 20% municipal effluent, the highest
      concentration in the St. Lawrence River. Hepatic RNA was extracted and used to
      hybridize a fathead minnow oligonucleotide microarray containing approximately
      15k gene sequences. A total of 1300 genes were differentially expressed, of which
      309 genes had more than 2-fold change in expression level between control and
      MWWE-exposed fish. Of those, 118 were up-regulated and 191 were down-regulated.
      Altered genes grouped according to function, indicated effects on various
      signaling pathways, apoptosis, immune responses, and cellular metabolism. Pathway
      analysis software predicted at least 5 signaling pathways that were altered by
      treatment: cell adhesion, inflammation, various kinases, estrogen receptor
      signaling and WNT signaling. Various components of the canonical Wnt pathway were
      dramatically down-regulated, while several other genes involved in the non
      canonical Wnt pathway, such as Wnt4, LRP6, and PPP2R5E, which are known to
      inhibit the canonical Wnt pathway, were increased. These results indicate that
      municipal wastewater effluent from Montreal can target and inhibit various
      signaling including those implicated in hepatic Wnt signaling pathway in fathead
      minnows.

PMID- 24747327
TI  - Perfluoroalkyl acids and the isomers of perfluorooctanesulfonate and
      perfluorooctanoate in the sera of 50 new couples in Tianjin, China.
AB  - A total of 100 serum samples from 50 new couples (none of the females in this
      study has ever been pregnant) in Tianjin, North China, were analyzed for eleven
      perfluoroalkyl acids (PFAAs) with isomer-specific method. Among all samples,
      total perfluorooctanesulfonate (?PFOS, mean 11.3 ng/mL) was predominant followed
      by total perfluorooctanoate (?PFOA, 2.95 ng/mL), perfluorodecanoate (PFDA, 1.17
      ng/mL), perfluorononanoate (PFNA, 0.93 ng/mL) and perfluorohexanesulfonate
      (PFHxS, 0.67 ng/mL). The mean concentrations of ?PFOS and PFHxS in males (14.2
      and 0.89 ng/mL) were significantly higher (p=0.001) than in females (8.36 and
      0.45 ng/mL). No statistical difference between genders was observed for the other
      PFAAs. This suggests that menstruation is one important elimination pathway for
      ?PFOS and PFHxS in females. Linear PFOA was the dominant isomer with mean
      proportion of 99.7%, suggesting that telomeric PFOA (and its precursors), which
      contains almost pure linear isomer, might be the dominant exposure source of PFOA
      in Tianjin. On average, the proportion of linear PFOS (n-PFOS) was 59.2% of
      ?PFOS, which was lower than that in technical PFOS products (ca. 70% linear).
      Except perfluoroisopropyl PFOS, all the other monomethyl branched PFOS isomers
      were enriched in human serum compared to the commercial products, suggesting the
      monomethyl branched PFOS precursors were preferentially biotransformed in humans.

PMID- 24747328
TI  - Assessing the risk of an excess fluoride intake among Swedish children in
      households with private wells--expanding static single-source methods to a
      probabilistic multi-exposure-pathway approach.
AB  - It is often assumed that water consumption is the major route of exposure for
      fluoride and analysis of water fluoride content is the most common approach for
      ensuring that the daily intake is not too high. In the present study, the risk of
      excess intake was characterized for children in households with private wells in
      Kalmar County, Sweden, where the natural geology shows local enrichments in
      fluorine. By comparing water concentrations with the WHO drinking water guideline
      (1.5 mg/L), it was found that 24% of the ca. 4800 sampled wells had a
      concentration above this limit, hence providing a figure for the number of
      children in the households concerned assessed to be at risk using this
      straightforward approach. The risk of an excess intake could, alternatively, also
      be characterized based on a tolerable daily intake (in this case the US EPA RfD
      of 0.06 mg/kg-day). The exposure to be evaluated was calculated using a
      probabilistic approach, where the variability in all exposure factors was
      considered, again for the same study population. The proportion of children
      assessed to be at risk after exposure from drinking water now increased to 48%,
      and when the probabilistic model was adjusted to also include other possible
      exposure pathways; beverages and food, ingestion of toothpaste, oral soil intake
      and dust inhalation, the number increased to 77%. Firstly, these results show how
      the risk characterization is affected by the basis of comparison. In this
      example, both of the reference values used are widely acknowledged. Secondly, it
      illustrates how much of the total exposure may be overlooked when only focusing
      on one exposure pathway, and thirdly, it shows the importance of considering the
      variability in all relevant pathways.

PMID- 24747329
TI  - Novel structure-driven features for accurate prediction of protein structural
      class.
AB  - Prediction of protein structural class plays an important role in inferring
      tertiary structure and function of a protein. Extracting good representation from
      protein sequence is fundamental for this prediction task. In this paper, a novel
      computational method is proposed to predict protein structural class solely from
      the predicted secondary structure information. A total of 27 features rationally
      divided into 3 different groups are extracted to characterize general contents
      and spatial arrangements of the predicted secondary structural elements. Then, a
      multi-class nonlinear support vector machine classifier is used to implement
      prediction. Various prediction accuracies evaluated by the jackknife cross
      validation test are reported on four widely-used low-homology benchmark datasets.
      Comparing with the state-of-the-art in protein structural class prediction, the
      proposed method achieves the highest overall accuracies on all the four datasets.
      The experimental results confirm that the proposed structure-driven features are
      very useful for accurate prediction of protein structural class. 

PMID- 24747330
TI  - Vibrational spectroscopic study and NBO analysis on tranexamic acid using DFT
      method.
AB  - In this work, we reported the vibrational spectra of tranexamic acid (TA) by
      experimental and quantum chemical calculation. The solid phase FT-Raman and FT-IR
      spectra of the title compound were recorded in the region 4000 cm(-1) to 100 cm(
      1) and 4000 cm(-1) to 400 cm(-1) respectively. The molecular geometry, harmonic
      vibrational frequencies and bonding features of TA in the ground state have been
      calculated by using density functional theory (DFT) B3LYP method with standard 6
      31G(d,p) basis set. The scaled theoretical wavenumber showed very good agreement
      with the experimental values. The vibrational assignments were performed on the
      basis of the potential energy distribution (PED) of the vibrational modes.
      Stability of the molecule, arising from hyperconjugative interactions and charge
      delocalization, has been analyzed using Natural Bond Orbital (NBO) analysis. The
      results show that ED in the sigma(*) and pi(*) antibonding orbitals and second
      order delocalization energies E(2) confirm the occurrence of intramolecular
      charge transfer (ICT) within the molecule. The electrostatic potential mapped
      onto an isodensity surface has been obtained. The calculated HOMO and LUMO
      energies show that charge transfer occurs within the molecule. The thermodynamic
      properties (heat capacity, entropy, and enthalpy) of the title compound at
      different temperatures were calculated in gas phase.

PMID- 24747331
TI  - Analysis of structure origin and luminescence properties of Yb(3+)-Er(3+) co
      doped fluorophosphate glass.
AB  - The near infrared luminescence properties of Yb(3+)-Er(3+) co-doped
      fluorophosphate glasses have been investigated. The various effects on structure
      and 1.53 MUm emission were analyzed as a function of Yb(3+) concentration. The
      energy transfer mechanism was proposed. High measured lifetime (10.75 ms), large
      effective full widths at half maximum (73.71 nm) and large gain per unit length
      (62.8 * 10(-)(24)cm(2)s) have been achieved in prepared glass. The present glass
      co-doped with 6mol% YbF3 and 2 mol% ErF3 showed magnificent luminescence
      properties for telecommunication application.

PMID- 24747332
TI  - Synthesis, characterization and quantum chemical investigation of molecular
      structure and vibrational spectra of 2,5-dichloro-3,6-bis-(methylamino)1,4
      benzoquinone.
AB  - 2,5-Dichloro-3,6-bis-methylamino-[1,4]benzoquinone has been synthesized by
      condensing methyl amine hydrochloride with chloranil in presence of condensing
      agent sodium acetate. FT-IR (4000-400 cm(-1)) and FT-Raman (4000-400 cm(-1))
      spectral measurements of dmdb have been done. Ab initio and DFT (B3LYP/6
      311+G(**)) calculations have been performed giving energies, optimized
      structures, harmonic vibrational frequencies, infrared intensities and Raman
      activities. The optimized molecular structure of the compound is found to possess
      C2h point group symmetry. A detailed interpretation of the observed IR and Raman
      spectra of dmdb is reported on the basis of the calculated potential energy
      distribution. Stability of the molecule arising from hyper conjugative
      interactions, charge delocalization has been analyzed using NBO analysis. The
      HOMO and LUMO energy gap reveals that the energy gap reflects the chemical
      activity of the molecule. The thermodynamic functions of the title compound have
      also been computed.

PMID- 24747333
TI  - Distinguishing induced fit from conformational selection.
AB  - The interactions between proteins and ligands often involve a conformational
      change in the protein. This conformational change can occur before
      (conformational selection) or after (induced fit) the association with ligand. It
      is often very difficult to distinguish induced fit from conformational selection
      when hyperbolic binding kinetics are observed. In light of a recent paper in this
      journal (Vogt et al., Biophys. Chem., 186, 2014, 13-21) and the current interest
      in binding mechanisms emerging from observed sampling of distinct conformations
      in protein domains, as well as from the field of intrinsically disordered
      proteins, we here describe a kinetic method that, at least in some cases,
      unequivocally distinguishes induced fit from conformational selection. The method
      relies on measuring the observed rate constant lambda for binding and varying
      both the protein and the ligand in separate experiments. Whereas induced fit
      always yields a hyperbolic dependence of increasing lambda values, the
      conformational selection mechanism gives rise to distinct kinetics when the
      ligand and protein (displaying the conformational change) concentration is varied
      in separate experiments. We provide examples from the literature and discuss the
      limitations of the approach. 

PMID- 24747334
TI  - Superior survival of unmanipulated haploidentical hematopoietic stem cell
      transplantation compared with chemotherapy alone used as post-remission therapy
      in adults with standard-risk acute lymphoblastic leukemia in first complete
      remission.
AB  - We wanted to compare the efficacy of haploidentical hematopoietic stem cell
      transplantation (HSCT) with chemotherapy alone in adults with standard-risk acute
      lymphoblastic leukemia (ALL) in first complete remission (CR1). One hundred
      thirty-eight consecutive adult patients with standard-risk ALL in CR1 were
      retrospectively investigated. Of these patients, 59 received chemotherapy alone
      (group A) and 79 received unmanipulated haploidentical HSCT (group B). Cumulative
      incidence of relapse at 5 years in group A was significantly higher than that in
      group B (66.3% versus 29.9%, P < .0001). Overall and disease-free survival in
      group A were significantly inferior to group B (P < .0001). Moreover,
      multivariate analyses demonstrated that central nervous system leukemia (P =
      .002), T cell immunophenotype (P = .044), expression of E2A-PBX1 (P = .007), and
      positive minimal residual disease after the first cycle of consolidation (P =
      .004) were correlated with relapse. Patients with 1 of 4 risk factors were
      assigned to the high-risk group. Otherwise, patients without risk factors were
      assigned to the low-risk group. In the high-risk group, HSCT had lower relapse
      rates and superior DFS compared with chemotherapy (P < .05), but in the low-risk
      group, there were no differences between HSCT and chemotherapy (P > .05). This
      study is the first to demonstrate that compared with chemotherapy alone,
      haploidentical HSCT is a better postremission therapy in adults with standard
      risk ALL in CR1. Moreover, based on the 4 risk factors, the establishment of risk
      stratification could identify the subgroup of patients with a higher risk of
      relapse in adults with standard-risk ALL in CR1. Furthermore, risk stratification
      directed postremission therapies using haploidentical HSCT or chemotherapy alone
      not only reduce relapse rate but also avoid unnecessary treatment-related
      mortality and improve survival. 

PMID- 24747336
TI  - Total body irradiation and cyclophosphamide plus antithymocyte globulin regimen
      is well tolerated and promotes stable engraftment as a preparative regimen before
      T cell-replete haploidentical transplantation for acute leukemia.
AB  - We compared total body irradiation (TBI, 700 cGy)/cyclophosphamide (Cy, 3.6
      g/m(2))/simustine (250 mg/m(2)) plus antithymocyte globulin (ATG) (TBI/Cy plus
      ATG) with cytarabine (8 g/m(2))/i.v. busulfan (Bu, 9.6 mg/kg)/Cy (3.6
      g/m(2))/simustine (250 mg/m(2)) plus ATG (modified Bu/Cy plus ATG) as preparative
      therapy in T cell-replete haploidentical hematopoietic stem cell transplantation
      (haplo-HSCT) for acute leukemia. From August 2009 to August 2013, 38 consecutive
      patients using TBI/Cy plus ATG regimen for T cell-replete haplo-HSCT (TBI group)
      at our center were eligible, which contained 28 high-risk and 10 standard-risk
      patients. A nested case-control study was designed. Seventy-seven patients using
      modified Bu/Cy plus ATG regimen (Bu group) were randomly selected in a 1 to 3:1
      ratio matching for age, disease and status, year of HSCT (+/-2 years), and length
      of follow-up. Only 1 graft failure occurred in the TBI group. The incidence and
      time of neutrophil and platelet engraftment were comparable between the 2 groups.
      Severe grades III/IV graft-versus-host disease was observed in 13.4% of Bu group
      and only 2.6% of TBI group (P = .083). More toxicity of the liver (37.7% versus
      10.5%; P = .002) and more hemorrhagic cystitis occurred in the Bu group (49.3%
      versus 23.7%, P = .008). Diarrhea was more common in the TBI group (44.7% versus
      22.1%; P = .031). No significant differences were found in the 2-year incidences
      of relapse (26.5% for TBI group versus 32.3% for Bu group, P = .742), 1-year
      transplant-related mortality (12.6% versus 16.2%, P = .862), 2-year overall
      survival (60.2% versus 57.0%, P = .937), and 2-year incidence of disease-free
      survival (57.9% versus 56.6%, P = .845) between the 2 groups. We conclude that
      the TBI/Cy plus ATG regimen seems to be feasible in T cell-replete haplo-HSCT,
      which promotes stable engraftment and a lower incidence of liver toxicity and
      hemorrhagic cystitis. However, longer follow-up is necessary to determine the
      late relapse rate and late toxicity. 

PMID- 24747335
TI  - Sleep disruption in hematopoietic cell transplantation recipients: prevalence,
      severity, and clinical management.
AB  - Sleep disruption is common among hematopoietic cell transplant (HCT) recipients,
      with over 50% of recipients experiencing sleep disruption pre-transplant, with up
      to 82% of patients experiencing moderate to severe sleep disruption during
      hospitalization for transplant and up to 43% after transplant. These rates of
      sleep disruption are substantially higher than what we see in the general
      population. Although sleep disruption can be distressing to patients and
      contribute to diminished quality of life, it is rarely discussed during clinical
      visits. The goal of the current review is to draw attention to sleep disruption
      and disorders (ie, insomnia, obstructive sleep apnea, restless legs syndrome) as
      a clinical problem in HCT in order to facilitate patient education, intervention,
      and research. We identified 35 observational studies published in the past decade
      that examined sleep disruption or disorders in HCT. Most studies utilized a
      single item measure of sleep, had small sample size, and included heterogeneous
      samples of patients. Six studies of the effects of psychosocial and exercise
      interventions on sleep in HCT have reported no significant improvements. These
      results highlight the need for rigorous observational and interventional studies
      of sleep disruption and disorders in HCT recipients.. 

PMID- 24747337
TI  - Brain slice biotinylation: an ex vivo approach to measure region-specific plasma
      membrane protein trafficking in adult neurons.
AB  - Regulated endocytic trafficking is the central mechanism facilitating a variety
      of neuromodulatory events, by dynamically controlling receptor, ion channel, and
      transporter cell surface presentation on a minutes time scale. There is a broad
      diversity of mechanisms that control endocytic trafficking of individual
      proteins. Studies investigating the molecular underpinnings of trafficking have
      primarily relied upon surface biotinylation to quantitatively measure changes in
      membrane protein surface expression in response to exogenous stimuli and gene
      manipulation. However, this approach has been mainly limited to cultured cells,
      which may not faithfully reflect the physiologically relevant mechanisms at play
      in adult neurons. Moreover, cultured cell approaches may underestimate region
      specific differences in trafficking mechanisms. Here, we describe an approach
      that extends cell surface biotinylation to the acute brain slice preparation. We
      demonstrate that this method provides a high-fidelity approach to measure rapid
      changes in membrane protein surface levels in adult neurons. This approach is
      likely to have broad utility in the field of neuronal endocytic trafficking. 

PMID- 24747338
TI  - CC chemokine ligand 18 and IGF-binding protein 6 as potential serum biomarkers
      for prostate cancer.
AB  - Prostate cancer (PCa) is the second leading cause of cancer-related death in men
      globally. However, there are few sensitive biomarkers for PCa, especially those
      which can distinguish PCa and benign prostate hyperplasia (BPH). Antibody
      microarrays allow for high-throughput and high-sensitivity detection of multiple
      proteins simultaneously, providing a powerful tool for biomarker screening. Here,
      we selected 46 patients with PCa and 42 controls with BPH, and compared the serum
      levels of different cytokines in PCa and BPH patients using antibody microarrays.
      The results indicated that serum levels of macrophage colony-stimulating factor
      (M-CSF) and CC chemokine ligand 18 (CCL-18) were remarkably higher in PCa
      patients than those in BPH patients, while serum levels of insulin-like growth
      factor-binding protein 6 (IGFBP-6) and Fas receptor (Fas), also called tumor
      necrosis factor receptor superfamily member 6 (TNFRSF6), were significantly
      lower. M-CSF and Fas/TNFRSF6 have been reported to be associated with PCa
      pathogenesis, and thus were used as positive controls in the present study. CCL
      18 is a chemokine primarily involved in recruitment of the adaptive immune
      system, while IGFBP-6 has been reported to inhibit proliferation of PCa cells.
      Serum levels of these four cytokines could distinguish PCa from BPH with high
      sensitivity and high specificity. Furthermore, the area under the ROC curve (AUC)
      was above 0.925 and 0.835 for CCL-18 and IGFBP-6, respectively, implying their
      high diagnostic value. In conclusion, we have identified CCL-18 and IGFBP-6 as
      new potential serum biomarkers for PCa. 

PMID- 24747339
TI  - Bioenergetics and the oxidative burst: protocols for the isolation and evaluation
      of human leukocytes and platelets.
AB  - Mitochondrial dysfunction is known to play a significant role in a number of
      pathological conditions such as atherosclerosis, diabetes, septic shock, and
      neurodegenerative diseases but assessing changes in bioenergetic function in
      patients is challenging. Although diseases such as diabetes or atherosclerosis
      present clinically with specific organ impairment, the systemic components of the
      pathology, such as hyperglycemia or inflammation, can alter bioenergetic function
      in circulating leukocytes or platelets. This concept has been recognized for some
      time but its widespread application has been constrained by the large number of
      primary cells needed for bioenergetic analysis. This technical limitation has
      been overcome by combining the specificity of the magnetic bead isolation
      techniques, cell adhesion techniques, which allow cells to be attached without
      activation to microplates, and the sensitivity of new technologies designed for
      high throughput microplate respirometry. An example of this equipment is the
      extracellular flux analyzer. Such instrumentation typically uses oxygen and pH
      sensitive probes to measure rates of change in these parameters in adherent
      cells, which can then be related to metabolism. Here we detail the methods for
      the isolation and plating of monocytes, lymphocytes, neutrophils and platelets,
      without activation, from human blood and the analysis of mitochondrial
      bioenergetic function in these cells. In addition, we demonstrate how the
      oxidative burst in monocytes and neutrophils can also be measured in the same
      samples. Since these methods use only 8-20 ml human blood they have potential for
      monitoring reactive oxygen species generation and bioenergetics in a clinical
      setting.

PMID- 24747340
TI  - Endocannabinoid-mediated retrograde modulation of synaptic transmission.
AB  - One of the two major endocannabinoids, 2-arachidonoylglycerol (2-AG), serves as a
      retrograde messenger at various types of synapses throughout the brain. Upon
      postsynaptic activation, 2-AG is released immediately after de novo synthesis,
      activates presynaptic CB1 cannabinoid receptors, and transiently suppresses
      neurotransmitter release. When CB1 receptor activation is combined with some
      other factors such as presynaptic activity, the suppression is converted to a
      long-lasting form. Whereas 2-AG primarily transmits a rapid, transient, point-to
      point retrograde signal, the other major endocannabinoid, anandamide, may
      function as a relatively slow retrograde or non-retrograde signal or as an
      agonist of the vanilloid receptor. The endocannabinoid system can be up- or down
      regulated by a variety of physiological and environmental factors including
      stress, which might be clinically important. 

PMID- 24747341
TI  - Brain-derived neurotrophic factor promotes gephyrin protein expression and GABAA
      receptor clustering in immature cultured hippocampal cells.
AB  - Fast synaptic inhibition in the adult brain is largely mediated by GABAA
      receptors (GABAAR). GABAAR are anchored to synaptic sites by gephyrin, a
      scaffolding protein that appears to be assembled as a hexagonal lattice beneath
      the plasma membrane. Brain derived neurotrophic factor (BDNF) alters the
      clustering and synaptic distribution of GABAAR but mechanisms behind this
      regulation are just starting to emerge. The current study was aimed to examine if
      BDNF alters the protein levels and/or clustering of gephyrin and to investigate
      whether the modulation of gephyrin is accompanied by changes in the distribution
      and/or clustering of GABAAR. Exogenous application of BDNF to immature neuronal
      cultures from rat hippocampus increased the protein levels and clustering of
      gephyrin. BDNF also augmented the association of gephyrin with GABAAR and
      promoted the formation of GABAAR clusters. Together, these observations indicate
      that BDNF might regulate the assembly of GABAergic synapses by promoting the
      association of GABAAR with gephyrin. 

PMID- 24747342
TI  - Bradykinin postconditioning ameliorates focal cerebral ischemia in the rat.
AB  - The goal of this study is to investigate the effects of bradykinin (BR)
      postconditioning on cerebral ischemic injury. Transient focal cerebral ischemia
      was induced in rats by 60min of middle cerebral artery occlusion (MCAO), followed
      by 3days of reperfusion. BR as a postconditioner at a dose of 150MUg/kg was
      applied intraperitoneally 3, 6, 24 and 48h after MCAO. BR postconditioning
      significantly reduced total infarct volumes if applied 3h after MCAO by 95%, 6h
      after MCAO by 80% and 24h after MCAO by 70% in versus vehicle group. Neurological
      functions were amarked improvement in the BR groups compared to the ischemia
      group. The number of degenerated neurons in the hippocampal CA1 region was also
      significantly lower in BR-treated ischemic groups compared to vehicle group. BR
      postconditioning prevented the release of MnSOD from the mitochondria and reduced
      the activity of the total SOD and CAT if it is administrated short time after
      stroke. Our data proves the ischemic tolerance in the brain induced by BR
      postconditioning resulted as effective agent against as strong an attack as 60min
      MCAO even when used many hours after ischemia. 

PMID- 24747344
TI  - Toward an understanding of the gene-specific and global logic of inducible gene
      transcription.
AB  - Virtually all living organisms have evolved mechanisms to adapt to their
      environment by sensing environmental stresses and inducing the transcription of
      appropriate sets of response genes in a coordinated fashion. In the vertebrate
      immune system, the highly selective response to an environmental stimulus, often
      an invading microorganism, plays an especially important role in regulating the
      activities of, and interactions among, the many cell types involved in innate and
      adaptive immunity. It is now widely appreciated that the selective response to a
      stimulus requires the concerted action of signal transduction pathways,
      transcription factors, and chromatin structure. Many proteins and pathways that
      help to regulate a response have been characterized. However, our understanding
      of the gene-specific and global logic through which a highly selective response
      is elicited has only recently begun to emerge. 

PMID- 24747343
TI  - Reproductive neuroendocrine dysfunction in polycystic ovary syndrome: insight
      from animal models.
AB  - Polycystic ovary syndrome (PCOS) is a common endocrinopathy with elusive origins.
      A clinically heterogeneous disorder, PCOS is likely to have multiple etiologies
      comprised of both genetic and environmental factors. Reproductive neuroendocrine
      dysfunction involving increased frequency and amplitude of gonadotropin-releasing
      hormone (GnRH) release, as reflected by pulsatile luteinizing hormone (LH)
      secretion, is an important pathophysiologic component in PCOS. Whether this
      defect is primary or secondary to other changes in PCOS is unclear, but it
      contributes significantly to ongoing reproductive dysfunction. This review
      highlights recent work in animal models, with a particular emphasis on the mouse,
      demonstrating the ability of pre- and postnatal steroidal and metabolic factors
      to drive changes in GnRH/LH pulsatility and GnRH neuron function consistent with
      the observed abnormalities in PCOS. This work has begun to elucidate how a
      complex interplay of ovarian, metabolic, and neuroendocrine factors culminates in
      this syndrome. 

PMID- 24747345
TI  - Short-term exposure to dimethylformamide and the impact on digestive system
      disease: an outdoor study for volatile organic compound.
AB  - Occupational and experimental studies have revealed the organs most affected by
      dimethylformamide (DMF) are liver and gastrointestinal tract. However, few
      studies have focused on the potential effect of outdoor pollution of DMF. This
      study examined the health risk of hospitalization due to digestive system disease
      by time series studies in a case city Longwan, China. The urine metabolite of DMF
      was correlated well with DMF exposure concentration (EC). A 101.0-MUg/m(3)
      (interquartile range) increase in the two-day moving average of DMF EC was
      associated with a 1.10 (1.01 ~ 1.20), 1.22 (1.10 ~ 1.35), and 1.05 (0.90 ~ 1.22)
      increase in hospitalization for total digestive system diseases, liver disease,
      and gastrointestinal tract disease, respectively. The exposure-dose response
      between DMF and the relative risk of liver disease was linear only below 350
      MUg/m(3). These findings highlight a previously unrecognized health problem
      related to VOCs released into the outdoor environment. 

PMID- 24747346
TI  - Urban ecosystem modeling and global change: potential for rational urban
      management and emissions mitigation.
AB  - Urbanization is a strong and extensive driver that causes environmental pollution
      and climate change from local to global scale. Modeling cities as ecosystems has
      been initiated by a wide range of scientists as a key to addressing challenging
      problems concomitant with urbanization. In this paper, 'urban ecosystem modeling
      (UEM)' is defined in an inter-disciplinary context to acquire a broad perception
      of urban ecological properties and their interactions with global change.
      Furthermore, state-of-the-art models of urban ecosystems are reviewed,
      categorized as top-down models (including materials/energy-oriented models and
      structure-oriented models), bottom-up models (including land use-oriented models
      and infrastructure-oriented models), or hybrid models thereof. Based on the
      review of UEM studies, a future framework for explicit UEM is proposed based the
      integration of UEM approaches of different scales, guiding more rational urban
      management and efficient emissions mitigation. 

PMID- 24747347
TI  - Characterizing the influence of highways on springtime NO2 and NH3 concentrations
      in regional forest monitoring plots.
AB  - Highways are major sources of nitrogen dioxide (NO2) and ammonia (NH3). In this
      study, springtime NO2 and NH3 concentrations were measured at 17 Ontario Forest
      Biomonitoring Network (OFBN) plots using passive samplers. Average springtime NO2
      concentrations were between 1.3 MUg m(-3) and 27 MUg m(-3), and NH3
      concentrations were between 0.2 MUg m(-3) and 1.7 MUg m(-3), although
      concentrations measured in May (before leaf out) were typically twice as high as
      values recorded in June. Average NO2 concentrations, and to a lesser extent NH3,
      could be predicted by road density at all radii (around the plot) tested (500 m,
      1000 m, 1500 m). Springtime NO2 concentrations were predicted for a further 50
      OFBN sites. Normalized plant/lichen N concentrations were positively correlated
      with estimated springtime NO2 and NH3 concentrations. Epiphytic foliose lichen
      richness decreased with increasing NO2 and NH3, but vascular plant richness was
      positively related to estimated springtime NO2 and NH3. 

PMID- 24747349
TI  - Polycyclic aromatic hydrocarbons in coastal sediment of klang strait, Malaysia:
      distribution pattern, risk assessment and sources.
AB  - Concentration, source, and ecological risk of polycyclic aromatic hydrocarbons
      (PAHs) were investigated in 22 stations from surface sediments in the areas of
      anthropogenic pollution in the Klang Strait (Malaysia). The total PAH level in
      the Klang Strait sediment was 994.02+/-918.1 ug/kg dw. The highest concentration
      was observed in stations near the coastline and mouth of the Klang River. These
      locations were dominated by high molecular weight PAHs. The results showed both
      pyrogenic and petrogenic sources are main sources of PAHs. Further analyses
      indicated that PAHs primarily originated from pyrogenic sources (coal combustion
      and vehicular emissions), with significant contribution from petroleum inputs.
      Regarding ecological risk estimation, only station 13 was moderately polluted,
      the rest of the stations suffered rare or slight adverse biological effects with
      PAH exposure in surface sediment, suggesting that PAHs are not considered as
      contaminants of concern in the Klang Strait. 

PMID- 24747350
TI  - Production and analysis of perdeuterated lipids from Pichia pastoris cells.
AB  - Probing molecules using perdeuteration (i.e deuteration in which all hydrogen
      atoms are replaced by deuterium) is extremely useful in a wide range of
      biophysical techniques. In the case of lipids, the synthesis of the biologically
      relevant unsaturated perdeuterated lipids is challenging and not usually pursued.
      In this work, perdeuterated phospholipids and sterols from the yeast Pichia
      pastoris grown in deuterated medium are extracted and analyzed as derivatives by
      gas chromatography and mass spectrometry respectively. When yeast cells are grown
      in a deuterated environment, the phospholipid homeostasis is maintained but the
      fatty acid unsaturation level is modified while the ergosterol synthesis is not
      affected by the deuterated culture medium. Our results confirm that the
      production of well defined natural unsaturated perdeuterated lipids is possible
      and gives also new insights about the process of desaturase enzymes. 

PMID- 24747351
TI  - Fabrication, vascularization and osteogenic properties of a novel synthetic
      biomimetic induced membrane for the treatment of large bone defects.
AB  - The induced membrane has been widely used in the treatment of large bone defects
      but continues to be limited by a relatively lengthy healing process and a
      requisite two stage surgical procedure. Here we report the development and
      characterization of a synthetic biomimetic induced membrane (BIM) consisting of
      an inner highly pre-vascularized cell sheet and an outer osteogenic layer using
      cell sheet engineering. The pre-vascularized inner layer was formed by seeding
      human umbilical vein endothelial cells (HUVECs) on a cell sheet comprised of a
      layer of undifferentiated human bone marrow-derived mesenchymal stem cells
      (hMSCs). The outer osteogenic layer was formed by inducing osteogenic
      differentiation of hMSCs. In vitro results indicated that the undifferentiated
      hMSC cell sheet facilitated the alignment of HUVECs and significantly promoted
      the formation of vascular-like networks. Furthermore, seeded HUVECs rearranged
      the extracellular matrix produced by hMSC sheet. After subcutaneous implantation,
      the composite constructs showed rapid vascularization and anastomosis with the
      host vascular system, forming functional blood vessels in vivo. Osteogenic
      potential of the BIM was evidenced by immunohistochemistry staining of
      osteocalcin, tartrate-resistant acid phosphatase (TRAP) staining, and alizarin
      red staining. In summary, the synthetic BIM showed rapid vascularization,
      significant anastomoses, and osteogenic potential in vivo. This synthetic BIM has
      the potential for treatment of large bone defects in the absence of infection. 

PMID- 24747352
TI  - A large amount of microdamages in the cortical bone around fracture site in a
      patient of atypical femoral fracture after long-term bisphosphonate therapy.
AB  - A breast cancer patient developed an atypical femoral fracture after 9 years of
      bisphosphonate therapy for the treatment of multiple bone metastases. We
      histopathologically analyzed the femoral cortical bone at the fracture site and
      the iliac cancellous bone. Four months prior to the fracture, the patient had
      experienced pain in the right femur and underwent plain radiography and bone
      scintigraphy which revealed cortical thickening and radioisotope accumulation at
      each site, respectively. The patient had also experienced a non-traumatic
      fracture at the same site on the contralateral side 2 years earlier. Based on
      these findings, atypical femoral fracture was diagnosed and intramedullary
      nailing performed. A cortical bone specimen taken from near the fracture site
      during surgery showed marked microdamages, and analysis of the iliac cancellous
      bone specimen revealed severely suppressed bone turnover. These findings suggest
      that microdamage and severely suppressed bone turnover are associated with
      atypical femoral fracture reported in this patient with long-term bisphosphonate
      therapy.

PMID- 24747353
TI  - The association of myosin IB with actin waves in dictyostelium requires both the
      plasma membrane-binding site and actin-binding region in the myosin tail.
AB  - F-actin structures and their distribution are important determinants of the
      dynamic shapes and functions of eukaryotic cells. Actin waves are F-actin
      formations that move along the ventral cell membrane driven by actin
      polymerization. Dictyostelium myosin IB is associated with actin waves but its
      role in the wave is unknown. Myosin IB is a monomeric, non-filamentous myosin
      with a globular head that binds to F-actin and has motor activity, and a non
      helical tail comprising a basic region, a glycine-proline-glutamine-rich region
      and an SH3-domain. The basic region binds to acidic phospholipids in the plasma
      membrane through a short basic-hydrophobic site and the Gly-Pro-Gln region binds
      F-actin. In the current work we found that both the basic-hydrophobic site in the
      basic region and the Gly-Pro-Gln region of the tail are required for the
      association of myosin IB with actin waves. This is the first evidence that the
      Gly-Pro-Gln region is required for localization of myosin IB to a specific actin
      structure in situ. The head is not required for myosin IB association with actin
      waves but binding of the head to F-actin strengthens the association of myosin IB
      with waves and stabilizes waves. Neither the SH3-domain nor motor activity is
      required for association of myosin IB with actin waves. We conclude that myosin
      IB contributes to anchoring actin waves to the plasma membranes by binding of the
      basic-hydrophobic site to acidic phospholipids in the plasma membrane and binding
      of the Gly-Pro-Gln region to F-actin in the wave. 

PMID- 24747354
TI  - The use of fault reporting of medical equipment to identify latent design flaws.
AB  - BACKGROUND AND PURPOSE: Poor device design that fails to adequately account for
      user needs, cognition, and behavior is often responsible for use errors resulting
      in adverse events. This poor device design is also often latent, and could be
      responsible for "No Fault Found" (NFF) reporting, in which medical devices sent
      for repair by clinical users are found to be operating as intended. Unresolved
      NFF reports may contribute to incident under reporting, clinical user
      frustration, and biomedical engineering technologist inefficacy. This study uses
      human factors engineering methods to investigate the relationship between NFF
      reporting frequency and device usability. MATERIAL AND METHODS: An analysis of
      medical equipment maintenance data was conducted to identify devices with a high
      NFF reporting frequency. Subsequently, semi-structured interviews and heuristic
      evaluations were performed in order to identify potential usability issues.
      Finally, usability testing was conducted in order to validate that latent
      usability related design faults result in a higher frequency of NFF reporting.
      RESULTS: The analysis of medical equipment maintenance data identified six
      devices with a high NFF reporting frequency. Semi-structured interviews,
      heuristic evaluations and usability testing revealed that usability issues caused
      a significant portion of the NFF reports. Other factors suspected to contribute
      to increased NFF reporting include accessory issues, intermittent faults and
      environmental issues. Usability testing conducted on three of the devices
      revealed 23 latent usability related design faults. CONCLUSIONS: These findings
      demonstrate that latent usability related design faults manifest themselves as an
      increase in NFF reporting and that devices containing usability related design
      faults can be identified through an analysis of medical equipment maintenance
      data.

PMID- 24747355
TI  - Analysis of obstetricians' decision making on CTG recordings.
AB  - Interpretation of cardiotocogram (CTG) is a difficult task since its evaluation
      is complicated by a great inter- and intra-individual variability. Previous
      studies have predominantly analyzed clinicians' agreement on CTG evaluation based
      on quantitative measures (e.g. kappa coefficient) that do not offer any insight
      into clinical decision making. In this paper we aim to examine the agreement on
      evaluation in detail and provide data-driven analysis of clinical evaluation. For
      this study, nine obstetricians provided clinical evaluation of 634 CTG recordings
      (each ca. 60min long). We studied the agreement on evaluation and its dependence
      on the increasing number of clinicians involved in the final decision. We showed
      that despite of large number of clinicians the agreement on CTG evaluations is
      difficult to reach. The main reason is inherent inter- and intra-observer
      variability of CTG evaluation. Latent class model provides better and more
      natural way to aggregate the CTG evaluation than the majority voting especially
      for larger number of clinicians. Significant improvement was reached in
      particular for the pathological evaluation - giving a new insight into the
      process of CTG evaluation. Further, the analysis of latent class model revealed
      that clinicians unconsciously use four classes when evaluating CTG recordings,
      despite the fact that the clinical evaluation was based on FIGO guidelines where
      three classes are defined. 

PMID- 24747357
TI  - Noradrenaline neuron degeneration contributes to motor impairments and
      development of L-DOPA-induced dyskinesia in a rat model of Parkinson's disease.
AB  - Parkinson's disease (PD) is characterized by progressive loss of dopaminergic
      (DA) neurons in the substantia nigra. However, studies of post-mortem PD brains
      have shown that not only DA neurons but also the noradrenergic (NA) neurons in
      the locus coeruleus degenerate, and that the NA neurodegeneration may be as
      profound, and also precede degeneration of the midbrain DA neurons. Previous
      studies in animal models of PD have suggested that loss of forebrain NA will add
      to the development of motor symptoms in animals with lesions of the nigrostriatal
      DA neurons, but the results obtained in rodents have been inconclusive due to the
      shortcomings of the toxin, DSP-4, used to lesion the NA projections. Here, we
      have developed an alternative double-lesion paradigm using injections of 6-OHDA
      into striatum in combination with intraventricular injections of a powerful NA
      immunotoxin, anti-DBH-Saporin, to eliminate the NA neurons in the locus
      coeruleus, and associated pontine nuclei. Animals with combined DA and NA lesions
      were more prone to develop L-DOPA-induced dyskinesia, even at low L-DOPA doses,
      and they performed significantly worse in tests of reflexive and skilled paw use,
      the stepping and staircase tests, compared to DA-only lesioned rats. Post-mortem
      analysis revealed that NA depletion did not affect the degree of DA depletion, or
      the loss of tyrosine hydroxylase-positive innervation in the striatum. Cell loss
      in the substantia nigra was similar in both single and double lesioned animals,
      showing that the worsening effect was not due to increased loss of nigral DA
      neurons. The results show that damage to brainstem NA neurons, contributes to the
      development of motor impairments and the appearance of L-DOPA-induced dyskinesia
      in 6-OHDA lesioned rats, and provide support for the view that the development of
      motor symptoms and dyskinetic side effects in PD patients reflects the combined
      loss of midbrain DA neurons and NA neurons. 

PMID- 24747356
TI  - Visualization and analytics tools for infectious disease epidemiology: a
      systematic review.
AB  - BACKGROUND: A myriad of new tools and algorithms have been developed to help
      public health professionals analyze and visualize the complex data used in
      infectious disease control. To better understand approaches to meet these users'
      information needs, we conducted a systematic literature review focused on the
      landscape of infectious disease visualization tools for public health
      professionals, with a special emphasis on geographic information systems (GIS),
      molecular epidemiology, and social network analysis. The objectives of this
      review are to: (1) identify public health user needs and preferences for
      infectious disease information visualization tools; (2) identify existing
      infectious disease information visualization tools and characterize their
      architecture and features; (3) identify commonalities among approaches applied to
      different data types; and (4) describe tool usability evaluation efforts and
      barriers to the adoption of such tools. METHODS: We identified articles published
      in English from January 1, 1980 to June 30, 2013 from five bibliographic
      databases. Articles with a primary focus on infectious disease visualization
      tools, needs of public health users, or usability of information visualizations
      were included in the review. RESULTS: A total of 88 articles met our inclusion
      criteria. Users were found to have diverse needs, preferences and uses for
      infectious disease visualization tools, and the existing tools are
      correspondingly diverse. The architecture of the tools was inconsistently
      described, and few tools in the review discussed the incorporation of usability
      studies or plans for dissemination. Many studies identified concerns regarding
      data sharing, confidentiality and quality. Existing tools offer a range of
      features and functions that allow users to explore, analyze, and visualize their
      data, but the tools are often for siloed applications. Commonly cited barriers to
      widespread adoption included lack of organizational support, access issues, and
      misconceptions about tool use. DISCUSSION AND CONCLUSION: As the volume and
      complexity of infectious disease data increases, public health professionals must
      synthesize highly disparate data to facilitate communication with the public and
      inform decisions regarding measures to protect the public's health. Our review
      identified several themes: consideration of users' needs, preferences, and
      computer literacy; integration of tools into routine workflow; complications
      associated with understanding and use of visualizations; and the role of user
      trust and organizational support in the adoption of these tools. Interoperability
      also emerged as a prominent theme, highlighting challenges associated with the
      increasingly collaborative and interdisciplinary nature of infectious disease
      control and prevention. Future work should address methods for representing
      uncertainty and missing data to avoid misleading users as well as strategies to
      minimize cognitive overload.

PMID- 24747358
TI  - G-protein coupled receptor 6 deficiency alters striatal dopamine and cAMP
      concentrations and reduces dyskinesia in a mouse model of Parkinson's disease.
AB  - The orphan G-protein coupled receptor 6 (GPR6) is a constitutively active
      receptor which is positively coupled to the formation of cyclic adenosine-3',5'
      monophosphate (cAMP). GPR6 is predominantly expressed in striatopallidal neurons.
      Here, we investigated neurochemical and behavioural effects of Gpr6 deficiency in
      mice. Gpr6 depletion decreased in vivo cAMP tissue concentrations (20%) in the
      striatum. An increase of striatal tissue dopamine concentrations (10%) was found
      in Gpr6(-/-) mice, whereas basal extracellular dopamine levels were not changed
      compared with Gpr6(+/+) mice, as shown by in vivo microdialysis. Western blot
      analyses revealed no alteration in the expression and subcellular localisation of
      the dopamine D2 receptor in the striatum of Gpr6(-/-) mice, and the number of
      tyrosine hydroxylase positive neurons in the substantia nigra was unchanged.
      DARPP-32 (dopamine and cAMP-regulated phosphoprotein of 32kDa) expression in the
      striatum of Gpr6(-/-) mice was not altered, however, a twofold increase in the
      phosphorylation of DARPP-32 at Thr34 was detected in Gpr6(-/-) compared with
      Gpr6(+/+) mice. Gpr6(-/-) mice showed higher locomotor activity in the open
      field, which persisted after treatment with the dopamine D2 receptor antagonist
      haloperidol. They also displayed reduced abnormal involuntary movements after
      apomorphine and quinpirole treatment in the mouse dyskinesia model of Parkinson's
      disease. In conclusion, the depletion of Gpr6 reduces cAMP concentrations in the
      striatum and alters the striatal dopaminergic system. Gpr6 deficiency causes an
      interesting behavioural phenotype in the form of enhanced motor activity combined
      with reduced abnormal involuntary movements. These findings could offer an
      opportunity for the treatment of Parkinson's disease beyond dopamine replacement.

PMID- 24747359
TI  - Sex differences in human epilepsy.
AB  - In the majority of neuropsychiatric conditions, marked gender-based differences
      have been found in the epidemiology, clinical manifestations, and therapy of
      disease. Emerging data suggest that gender differences exist also in the
      epidemiology, and pathophysiology of epilepsy. The present review summarizes the
      current information regarding gender and epilepsy. These differences are regarded
      from the perspective of innate sex differences in cerebral morphology, structural
      and functional connections, and assuming that these differences may render men
      and women differently vulnerable to epileptogenicity. 

PMID- 24747360
TI  - Effects of vanadium (III, IV, V)-chlorodipicolinate on glycolysis and antioxidant
      status in the liver of STZ-induced diabetic rats.
AB  - Vanadium compounds exert various insulin-mimetic and anti-diabetic effects both
      in vitro and in vivo. Vanadium(III, IV, V)-chlorodipicolinate (Vdipic-Cl)
      compounds, including H[V(III)(dipic-Cl)2].5H2O (V3dipic-Cl), V(IV)O(dipic
      Cl)(H2O)2 (V4dipic-Cl) and K[V(V)O2(dipic-Cl)] (V5dipic-Cl), were synthesized
      with the indicated oxidation states. The present study was conducted to
      investigate if chemical valence and anti-oxidation effects of vanadium compounds
      are involved in the anti-diabetic effects observed in streptozotocin (STZ)
      induced diabetic rats treated with these vanadium compounds. V3dipic-Cl, V4dipic
      Cl, V5dipic-Cl, inorganic vanadium salts vanadyl sulfate (VOSO4) or sodium
      metavanadate (NaVO3) were orally administered in drinking water (50 MUgV/ml) to
      STZ-induced diabetic rats for 28 days. The results showed that Vdipic-Cl
      treatment significantly improved hyperglycemia and glucose intolerance, as well
      as increased hepatic glycogen synthesis in diabetic rats. The mRNA levels of key
      glycolytic enzymes in liver, phosphoenolpyruvate carboxykinase (PEPCK),
      glucokinase (GK), and L-pyruvate kinase (L-PK) altered in diabetic animals were
      significantly restored towards normal values by treatment with some of the
      vanadium compounds. Moreover, the diabetes elevated activities of aspartate
      aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase
      (ALP) in serum were significantly decreased after treatment with Vdipic-Cl
      complexes. Furthermore, treatment of diabetic rats with V4dipic-Cl and V5dipic-Cl
      compounds significantly reduced malondialdehyde (MDA) production and increased
      glutathione peroxidase (GSH-Px) and catalase (CAT) activities. These data suggest
      that vanadium compounds with the indicated chemical valence promote glycogen
      synthesis and recover suppressed glycolysis in the liver of diabetic rats due to
      their capacity to reduce oxidative stress by stimulating antioxidant enzymes.

PMID- 24747361
TI  - Effects of Mn-doping on the structure and biological properties of beta
      tricalcium phosphate.
AB  - Doping calcium phosphates with trace elements that exist in bone tissues is
      beneficial in terms of cell-material interactions and in vivo performance of the
      bone grafts made thereof. Manganese (Mn) is an essential element for normal
      growth and metabolism of bone tissues, but studies reporting the effects of Mn
      doping calcium phosphates are scarce. The present study investigated the
      influence of Mn-doping on the structure, morphology and biological properties of
      beta-tricalcium phosphate [beta-Ca3(PO4)2] (beta-TCP). Mn-doped (MnTCP) powders,
      with Mn contents varying from 0 to 10 mol%, were obtained through an aqueous
      precipitation method followed by heat treatment at 800  degrees C. The successful
      incorporation of Mn into beta-TCP structure was proved through quantitative X-ray
      diffraction (XRD) phase analysis coupled with structural Rietveld refinement.
      Increasing Mn concentrations led to decreasing trends of a- and c-axis lattice
      parameters, and Mn-doping also significantly affected the morphology of beta-TCP
      powders. In vitro proliferation and differentiation assays of MC3T3-E1
      osteoblastic-like cells, grown in the presence of the powders, revealed that the
      biological benefits of Mn-doped beta-TCP are limited to lower Mn incorporation
      levels and potentially related to their surface microstructure. The Mn1-betaTCP
      composition revealed the best set of bioactivity properties, potentially a good
      candidate for future applications of beta-TCP materials in osteoregeneration.

PMID- 24747362
TI  - Genome comparison of Candida orthopsilosis clinical strains reveals the existence
      of hybrids between two distinct subspecies.
AB  - The Candida parapsilosis species complex comprises a group of emerging human
      pathogens of varying virulence. This complex was recently subdivided into three
      different species: C. parapsilosis sensu stricto, C. metapsilosis, and C.
      orthopsilosis. Within the latter, at least two clearly distinct subspecies seem
      to be present among clinical isolates (Type 1 and Type 2). To gain insight into
      the genomic differences between these subspecies, we undertook the sequencing of
      a clinical isolate classified as Type 1 and compared it with the available
      sequence of a Type 2 clinical strain. Unexpectedly, the analysis of the newly
      sequenced strain revealed a highly heterozygous genome, which we show to be the
      consequence of a hybridization event between both identified subspecies. This
      implicitly suggests that C. orthopsilosis is able to mate, a so-far unanswered
      question. The resulting hybrid shows a chimeric genome that maintains a similar
      gene dosage from both parental lineages and displays ongoing loss of
      heterozygosity. Several of the differences found between the gene content in both
      strains relate to virulent-related families, with the hybrid strain presenting a
      higher copy number of genes coding for efflux pumps or secreted lipases.
      Remarkably, two clinical strains isolated from distant geographical locations
      (Texas and Singapore) are descendants of the same hybrid line, raising the
      intriguing possibility of a relationship between the hybridization event and the
      global spread of a virulent clone. 

PMID- 24747363
TI  - Are we taking full advantage of the growing number of pharmacological treatment
      options for osteoporosis?
AB  - We are becoming increasingly aware that the manner in which our skeleton ages is
      not uniform within and between populations. Pharmacological treatment options
      with the potential to combat age-related reductions in skeletal strength continue
      to become available on the market, notwithstanding our current inability to fully
      utilize these treatments by accounting for an individual's unique biomechanical
      needs. Revealing new molecular mechanisms that improve the targeted delivery of
      pharmaceuticals is important; however, this only addresses one part of the
      solution for differential age-related bone loss. To improve current treatment
      regimes, we must also consider specific biomechanical mechanisms that define how
      these molecular pathways ultimately impact whole bone fracture resistance. By
      improving our understanding of the relationship between molecular and
      biomechanical mechanisms, clinicians will be better equipped to take full
      advantage of the mounting pharmacological treatments available. Ultimately this
      will enable us to reduce fracture risk among the elderly more strategically, more
      effectively, and more economically. In this interest, the following review
      summarizes the biomechanical basis of current treatment strategies while defining
      how different biomechanical mechanisms lead to reduced fracture resistance. It is
      hoped that this may serve as a template for the identification of new targets for
      pharmacological treatments that will enable clinicians to personalize care so
      that fracture incidence may be globally reduced. 

PMID- 24747365
TI  - An exploration of the estrogen receptor transcription activity of capsaicin
      analogues via an integrated approach based on in silico prediction and in vitro
      assays.
AB  - Capsaicin has been considered as an alternative template of dichlorodiphenyl
      trichloroethane (DDT) in antifouling paint. However, information regarding the
      estrogenic activity of capsaicin analogues is rather limited in comparison to
      that of DDT analogues and their metabolites. We here explore the ER transcription
      activity of selected capsaicin analogues via an integrated approach based on in
      silico prediction and in vitro assays. Molecular simulation and the
      agonist/antagonist differential-docking screening identified 6
      iodonordihydrocapsaicin (6-I-CPS) as a weak ERalpha agonist, while anti
      estrogenicity was expected for N-arachidonoyldopamine, capsazepine,
      dihydrocapsaicin, trichostatin A, and capsaicin. On the contrary, the large
      volume of analogues, such as phorbol 12-phenylacetate 13-acetate 20-homovanillate
      and phorbol 12,13-dinonanoate 20-homovanillate, cannot fit well with the ER
      cavity. The result of MVLN assay was in accord with the in silico prediction. 6-I
      CPS was demonstrated to induce luciferase gene expression, while the other
      analogues of relatively small molecular volume reduced luciferase gene expression
      in MVLN cells, both in the absence and presence of estradiol. This finding
      suggested that the ER transcription activity of capsaicin analogues is generated
      at least partly through the ERalpha-mediated pathway. Moreover, receptor
      polymorphism analysis indicated that capsaicin analogues may exhibit diverse
      species selectivity for human beings and marine species.

PMID- 24747364
TI  - Crosstalk between beta-2-adrenoceptor and muscarinic acetylcholine receptors in
      the airway.
AB  - The M3 and M2 muscarinic acetylcholine receptors (mAChRs) and beta-2
      adrenoceptors (beta2ARs) are important regulators of airway cell function, and
      drugs targeting these receptors are among the first line drugs in the treatment
      of the obstructive lung diseases asthma and chronic obstructive lung disease
      (COPD). Cross-regulation or crosstalk between mAChRs and beta2ARs in airway
      smooth muscle (ASM) helps determine the contractile state of the muscle, thus
      airway diameter and resistance to airflow. In this review we will detail mAChR
      and beta2AR-signaling and crosstalk, focusing on events in the ASM cell but also
      addressing the function of these receptors in other cell types that impact airway
      physiology. We conclude by discussing how recent advances in GPCR pharmacology
      offer a unique opportunity to fine tune mAChR and beta2AR signaling and their
      crosstalk, and thereby produce superior therapeutics for obstructive lung and
      other diseases. 

PMID- 24747366
TI  - Lipid compartmentalization in the endosome system.
AB  - Lipids play an essential role in the structure of the endosomal membranes as well
      as in their dynamic rearrangement during the transport of internalized cargoes
      along the endocytic pathway. In this review, we discuss the function of endosomal
      lipids mainly in mammalian cells, focusing on two well-known components of the
      lipid rafts, sphingomyelin and cholesterol, as well as on three anionic
      phospholipids, phosphatidylserine, polyphosphoinositides and the atypical
      phospholipid, bis(monoacylglycero)phosphate/lysobisphosphatidic acid. We detail
      the structure, metabolism, distribution and role of these lipids in the endosome
      system as well as their importance in pathological conditions where modification
      of the endosomal membrane flow can lead to various diseases such as lipid-storage
      diseases, myopathies and neuropathies. 

PMID- 24747367
TI  - The identity of zona pellucida receptor on spermatozoa: an unresolved issue in
      developmental biology.
AB  - Mammalian oocytes are surrounded by an acellular zona pellucida (ZP).
      Fertilization begins when a capacitated spermatozoon binds to the ZP. Defective
      sperm-ZP interaction is a cause of male infertility and reduced fertilization
      rates in clinical assisted reproduction treatment. Despite the importance of
      spermatozoa-ZP binding, the mechanisms and regulation of the interaction are
      unclear partly due to the failure in the identification of ZP receptor on
      spermatozoa. Most of the previous studies assumed that the sperm ZP receptor is a
      single molecular species, and a number of potential candidates had been
      suggested. Yet none of them can be considered as the sole sperm ZP receptor.
      Accumulated evidence suggested that the sperm ZP receptor is a dynamic multi
      molecular structure requiring coordinated action of different proteins that are
      assembled into a functional complex during post-testicular maturation and
      capacitation. The complex components may include carbohydrate-binding, protein
      binding and acrosomal matrix proteins which work as a suite to mediate
      spermatozoa-ZP interaction. This article aims to review the latest insights in
      the identification of the sperm ZP receptor. Continued investigation of the area
      will provide considerable understanding of the regulation of fertilization that
      will be useful for practical application in human contraception and reproductive
      medicine. 

PMID- 24747368
TI  - Modulation of tolerogenic dendritic cells and autoimmunity.
AB  - A key function of dendritic cells (DCs) is to induce either immune tolerance or
      immune activation. Many new DC subsets are being recognized, and it is now clear
      that each DC subset has a specialized function. For example, different DC subsets
      may express different cell surface molecules and respond differently to
      activation by secretion of a unique cytokine profile. Apart from intrinsic
      differences among DC subsets, various immune modulators in the microenvironment
      may influence DC function; inappropriate DC function is closely related to the
      development of immune disorders. The most exciting recent advance in DC biology
      is appreciation of human DC subsets. In this review, we discuss functionally
      different mouse and human DC subsets both in lymphoid organs and non-lymphoid
      organs, the molecules that regulate DC function, and the emerging understanding
      of the contribution of DCs to autoimmune diseases. 

PMID- 24747369
TI  - Cellular foundations of mammary tubulogenesis.
AB  - The mammary gland is composed of a highly branched network of epithelial tubes,
      embedded within a complex stroma. The mammary epithelium originates during
      embryonic development from an epidermal placode. However, the majority of ductal
      elongation and bifurcation occurs postnatally, in response to steroid hormone and
      growth factor receptor signaling. The process of pubertal branching morphogenesis
      involves both elongation of the primary ducts across the length of the fat pad
      and a wave of secondary branching that elaborates the ductal network. Recent
      studies have revealed that mammary epithelial morphogenesis is accomplished by
      transitions between simple and stratified organization. During active
      morphogenesis, the epithelium is stratified, highly proliferative, has few
      intercellular junctions, and exhibits incomplete apico-basal polarity. In this
      review, we discuss recent advances in our understanding of the relationship
      between epithelial architecture, epithelial polarity, and ductal elongation. 

PMID- 24747370
TI  - Retropinacol/cross-pinacol coupling reactions--a catalytic access to 1,2
      unsymmetrical diols.
AB  - Unsymmetrical 1,2-diols are hardly accessible by reductive pinacol coupling
      processes. A successful execution of such a transformation is bound to a clear
      recognition and strict differentiation of two similar carbonyl compounds
      (aldehydes -> secondary 1,2-diols or ketones -> tertiary 1,2-diols). This fine
      tuning is still a challenge and an unsolved problem for an organic chemist. There
      exist several reports on successful execution of this transformation but they
      cannot be generalized. Herein we describe a catalytic direct pinacol coupling
      process which proceeds via a retropinacol/cross-pinacol coupling sequence. Thus,
      unsymmetrical substituted 1,2-diols can be accessed with almost quantitative
      yields by means of an operationally simple performance under very mild
      conditions. Artificial techniques, such as syringe-pump techniques or delayed
      additions of reactants are not necessary. The procedure we describe provides a
      very rapid access to cross-pinacol products (1,2-diols, vicinal diols). A further
      extension of this new process, e.g. an enantioselective performance could provide
      a very useful tool for the synthesis of unsymmetrical chiral 1,2-diols. 

PMID- 24747371
TI  - Factors affecting job satisfaction and their correlation with educational
      standards among dental assistants.
AB  - A disparity exists in the educational qualifications of dental assistants working
      in various public and private institutions in Riyadh, Saudi Arabia. The aim of
      this study was to assess the influence of professional and personal
      characteristics on job satisfaction among dental assistants. A cross-sectional
      survey was performed among dental assistants using a 24-item self-administered
      questionnaire. Multinomial logistic regression was used to assess the
      relationship between overall job satisfaction and other variables. The overall
      response rate was 72.1%. Factor analysis suggested that five underlying factors
      were related to job satisfaction. The mean score for overall job satisfaction was
      3.86 (satisfied) out of 5. Among the work environment factors, the highest mean
      score, 4.26 (satisfied), was obtained for quality of service, and the lowest mean
      score, 2.78 (neutral), was obtained for the perception of income. The income and
      general prospects of the profession was significantly associated with overall job
      satisfaction. This study suggests that for dental assistants, professional and
      personal life, quality of service, perception of income and prestige and self
      respect are important factors for job satisfaction. Despite differences in
      professional formation standards, in general, the study participants were
      considerably satisfied with their jobs. 

PMID- 24747372
TI  - Assessing functional performance in the mdx mouse model.
AB  - Duchenne muscular dystrophy (DMD) is a severe and progressive muscle wasting
      disorder for which no cure is available. Nevertheless, several potential
      pharmaceutical compounds and gene therapy approaches have progressed into
      clinical trials. With improvement in muscle function being the most important end
      point in these trials, a lot of emphasis has been placed on setting up reliable,
      reproducible, and easy to perform functional tests to pre clinically assess
      muscle function, strength, condition, and coordination in the mdx mouse model for
      DMD. Both invasive and noninvasive tests are available. Tests that do not
      exacerbate the disease can be used to determine the natural history of the
      disease and the effects of therapeutic interventions (e.g. forelimb grip strength
      test, two different hanging tests using either a wire or a grid and rotarod
      running). Alternatively, forced treadmill running can be used to enhance disease
      progression and/or assess protective effects of therapeutic interventions on
      disease pathology. We here describe how to perform these most commonly used
      functional tests in a reliable and reproducible manner. Using these protocols
      based on standard operating procedures enables comparison of data between
      different laboratories. 

PMID- 24747373
TI  - Characterization of salt cake from secondary aluminum production.
AB  - Salt cake is a major waste component generated from the recycling of secondary
      aluminum processing (SAP) waste. Worldwide, the aluminum industry produces nearly
      5 million tons of waste annually and the end-of-life management of these wastes
      is becoming a challenge in the U.S. and elsewhere. In this study, the mineral
      phases, metal content and metal leachability of 39 SAP waste salt cake samples
      collected from 10 different facilities across the U.S. were determined. The
      results showed that aluminum (Al), aluminum oxide, aluminum nitride and its
      oxides, spinel and elpasolite are the dominant aluminum mineral phases in salt
      cake. The average total Al content was 14% (w/w). The overall percentage of the
      total leachable Al in salt cake was 0.6% with approximately 80% of the samples
      leaching at a level less than 1% of the total aluminum content. The extracted
      trace metal concentrations in deionized water were relatively low (MUgL(-1)
      level). The toxicity characteristic leaching procedure (TCLP) was employed to
      further evaluate leachability and the results indicated that the leached
      concentrations of toxic metals from salt cake were much lower than the EPA
      toxicity limit set by USEPA. 

PMID- 24747374
TI  - Copper recovery and gold enrichment from waste printed circuit boards by mediated
      electrochemical oxidation.
AB  - The present study aims to develop an eco-friendly chemical-electrochemical
      process for the simultaneous recovery of copper and separation of a gold rich
      residue from waste printed circuit boards (WPCBs). The process was carried out by
      employing two different types of reactors coupled in series: a leaching reactor
      with a perforated rotating drum, for the dissolution of base metals and a divided
      electrochemical reactor for the regeneration of the leaching solution with the
      parallel electrowinning of copper. The process performances were evaluated on the
      basis of the dissolution efficiency, current efficiency and specific energy
      consumptions. Finally a process scale up was realized taking into consideration
      the optimal values of the operating parameters. The laboratory scale leaching
      plant allowed the recovery of a high purity copper deposit (99.04wt.%) at a
      current efficiency of 63.84% and specific energy consumption of 1.75kWh/kg
      cooper. The gold concentration in the remained solid residue was 25 times higher
      than the gold concentration in the initial WPCB samples. 

PMID- 24747375
TI  - Comparison of chemical washing and physical cell-disruption approaches to assess
      the surface adsorption and internalization of cadmium by Cupriavidus
      metallidurans CH34.
AB  - Bacterial biosorption of heavy metals is often considered as a surface
      complexation process, without considering other retention compartments than cell
      walls. Although this approach gives a good description of the global biosorption
      process, it hardly permits the prediction of the fate of biosorbed metals in the
      environment. This study examines the subcellular distribution of cadmium (Cd) in
      the metal-tolerant bacterium Cupriavidus metallidurans CH34 through the
      comparison of an indirect chemical method (washing cells with EDTA) and a direct
      physical method (physical disruption of cells). The chemical washing approach
      presented strong experimental biases leading to the overestimation of washed
      amount of Cd, supposedly bound to cell membranes. On the contrary, the physical
      disruption approach gave reproducible and robust results of Cd subcellular
      distribution. Unexpectedly, these results showed that over 80% of passively
      biosorbed Cd is internalized in the cytoplasm. In disagreement with the common
      concept of surface complexation of metals onto bacteria the cell wall was poorly
      reactive to Cd. Our results indicate that metal sorption onto bacterial surfaces
      is only a first step in metal management by bacteria and open new perspectives on
      metal biosorption by bacteria in the environment, with implications for soil
      bioremediation or facilitated transport of metals by bacteria. 

PMID- 24747376
TI  - Reproductive toxicity in acrylamide-treated female mice.
AB  - We investigated the reproductive toxicity of acrylamide in female mice. The
      results from immunohistochemistry provided evidence that nitric oxide synthase
      (NOS) signaling was involved in the process of follicular development and
      atresia. Oral administration of acrylamide to female mice led to significantly
      reduced body weights, organ weights and the number of corpora lutea (P<0.05).
      Serum progesterone concentrations were significantly reduced (P<0.05) concomitant
      with the increasing doses of acrylamide; however, 17beta-estradiol (E2)
      concentrations were unchanged with treatment. Measurement of NOS activities
      indicated that total NOS (TNOS), iNOS and eNOS activities were significantly
      increased (P<0.05) with increasing doses of acrylamide. The results from in vitro
      study indicated that acrylamide reduced the viability of mouse granulosa cells in
      a dose-dependent manner. In summary, acrylamide affected bodily growth and
      development, as well as reproductive organs, the number of corpora lutea and
      progesterone production in female mice, possibly acting through the NOS signaling
      pathway. 

PMID- 24747377
TI  - The spillover effect of National Health Insurance on household consumption
      patterns: evidence from a natural experiment in Taiwan.
AB  - While providing financial risk protection was one of the major aims of
      introducing a National Health Insurance (NHI) program in Taiwan in 1995, one may
      also wonder how the households may exploit resources freed up and available to
      them as a result of reduced exposure to risk due to health insurance. This paper
      aims at studying and evaluating the impact of social insurance on these differing
      household consumption patterns. A differences-in-differences estimation model was
      applied to a sample of 17,899 households from the 1993-2000 Taiwan Survey of
      Family Income and Expenditure to assess the NHI's impact. This effect was
      evaluated by the changes in the proportion of the consumption expenditure devoted
      to medical items and non-medical items in the post-NHI period (1996-2000)
      compared to the pre-NHI period (1993-1994). Our study found that spending related
      to the improvement of housing conditions (rental and water bills) had the most
      significant increase, 1.87% (in the share). Furthermore, examining the NHI impact
      across socioeconomic status (SES) strata (in terms of income and education
      levels), our study found that households with the lowest SES experienced the
      largest increase in spending share (2.16%) for rental and water bills, and the
      least drop (0.64%) on education items. Recognizing how households can exploit the
      potential benefits associated with NHI provision could enable the government to
      devise specific policy tools to facilitate better targeting of investment
      decisions with limited resources available for less well-off households. 

PMID- 24747378
TI  - Gold mining on Mayan-Mam territory: social unravelling, discord and distress in
      the Western highlands of Guatemala.
AB  - This article examines the influence of a large-scale mining operation on the
      health of the community of San Miguel Ixtahuacan, Guatemala. An anti-colonial
      narrative approach informed by participatory action research principles was
      employed. Data collection included focus groups and one-on-one interviews from
      August to November of 2011. Over this period, we interviewed 15 Mam Mayan men and
      41 women (n = 56) between the ages of 18 and 64 including health care workers,
      educators, spiritual leaders, agricultural workers and previous mine employees
      from 13 villages within the municipality. Participants' accounts pointed to
      community health experiences of social unravelling characterized by overlapping
      narratives of a climate of fear and discord and embodied expressions of distress.
      These findings reveal the interconnected mechanisms by which local mining
      operations influenced the health of the community, specifically, by introducing
      new threats to the safety and mental wellbeing of local residents.

PMID- 24747379
TI  - Chemical modification of cellulose acetate by N-(phenyl amino) maleimides:
      characterization and properties.
AB  - Cellulose acetate (CA) was modified using N-(phenyl amino) maleimides (R-APhM)
      where, RH or 4-NO2. The structure of the modified polymer was characterized by
      (13)C-NMR. The chemical modification is based on the reaction between the acetyl
      group of the glucopyranose ring in cellulose acetate and the proton of the amino
      group in N-(phenyl amino) maleimide molecule. The thermal gravimetry (TGA) was
      used to investigate the thermal stability of the modified polymeric samples. The
      modified cellulose acetate by 4-nitro (phenyl amino) maleimide (CA/4-NO2APhM)
      exhibits the highest thermal stability as compared to the N-(phenyl amino)
      maleimide (CA/APhM) and the unmodified CA. The crystallinity and morphology of
      the modified polymeric samples were investigated using X-ray diffraction (XRD)
      and emission scanning electron microscope (ESEM), respectively. The presence of N
      (phenyl amino) maleimide moieties in the cellulose acetate matrix improved its
      mechanical property. Also, the organic nature of (R-APhM) moieties inside CA
      matrix reduced its wettability. 

PMID- 24747380
TI  - Preparation and characterization of bionanocomposite films based on potato
      starch/halloysite nanoclay.
AB  - In this research casting method was used to prepare potato starch based bio
      nanocomposite films with halloysite nanoclay as the reinforcing materials. The
      composition included potato starch with 40% (w/w) of a mixture of
      sorbitol/glycerol (weight ratio of 3 to 1as plasticizer) with nanoclay (0-5%
      w/w). The films were dried under controlled conditions. Physicochemical
      properties such as solubility in water, water absorption capacity (WAC), water
      vapour permeability (WVP), oxygen permeability, and mechanical properties of the
      films were measured. Results showed that by increasing the concentration of
      nanoclay, mechanical properties of films were improved. Tensile strength was
      increased from 7.33 to 9.82MPa, and elongation at break decreased from 68.0 to
      44.0%. Solubility in water decreased from 35 to 23%, and heat seal strength
      increased from 375 to 580N/m. Also incorporation of clay nanoparticles in the
      structure of biopolymer decreased permeability of the gaseous molecules. In
      summary, addition of halloysite nanoclay, improve the barrier and mechanical
      properties of potato starch films and this bionanocomposites have high potential
      to be used for food packaging purposes. 

PMID- 24747381
TI  - A study on antifungal activity of water-soluble chitosan against Macrophomina
      phaseolina.
AB  - The objective of this study was to evaluate antifungal effect of water-soluble
      chitosan (s-chitosan) on Macrophomina phaseolina (M. phaseolina) causing jute
      seedling infection and monitor the change in activity of released enzymes during
      infection. The minimum inhibitory concentration (MIC) of s-chitosan for M.
      phaseolina was found at 12.5g/l and s-chitosan exhibited fungistatic mode of
      action against this pathogen. The application of s-chitosan (12.5g/l) during
      infection of jute seedlings by M. phaseolina inhibited fungal infection and
      length of the seedlings was found almost similar to seedlings without infection.
      M. phaseolina infected jute seedlings showed length of 22mm over 10 days of
      incubation and it increased to 58mm in presence of s-chitosan (12.5g/l) during
      incubation for 10 days. TEM study indicated presence of hyphae in the cortical
      and epidermal cells of fungus infected jute seedlings indicating colonization by
      the fungus and it disappeared after treatment with s-chitosan. The changes in
      enzyme profiles of jute seedling during prevention of fungal infection using s
      chitosan helped in proper understanding of mode of action of s-chitosan as
      antifungal agent. The activity of defense related enzymes like chitosanase and
      peroxidase in infected seedlings was observed to be enhanced after treatment with
      s-chitosan. 

PMID- 24747382
TI  - Estimation of optimum specific light intensity per cell on a high-cell-density
      continuous culture of Chlorella zofingiensis not limited by nutrients or CO2.
AB  - To determine the optimum light intensity per cell required for rapid growth
      regardless of cell density, continuous cultures of the microalga Chlorella
      zofingiensis were grown with a sufficient supply of nutrients and CO2 and were
      subjected to different light intensities in the range of 75-1000 MUE m(-2) s(-1).
      The cell density of culture increased over time for all light conditions except
      for the early stage of the high light condition of 1000 MUE m(-2) s(-1). The
      light intensity per cell required for the high specific growth rate of 0.5 day(
      1) was determined to be 28-45 MUE g-ds(-1) s(-1). The specific growth rate was
      significantly correlated to light intensity (y=0.721*x/(66.98+x), r(2)=0.85,
      p<0.05). A high specific growth rate was maintained over a range of light
      intensities (250-1000 MUE m(-2) s(-1)). This range of light intensities suggested
      that effective production of C. zofingiensis can be maintained outdoors under
      strong light by using the optimum specific light intensity.

PMID- 24747383
TI  - Comparison between moving bed-membrane bioreactor (MB-MBR) and membrane
      bioreactor (MBR) systems: influence of wastewater salinity variation.
AB  - Two pilot plant systems were investigated for the treatment of wastewater subject
      to a gradual increase of salinity. In particular, a membrane bioreactor (MBR) and
      a moving bed biofilm membrane bioreactor (MB-MBR) were analyzed. Carbon and
      ammonium removal, kinetic constants and membranes fouling rates have been
      assessed. Both plants showed very high efficiency in terms of carbon and ammonium
      removal and the gradual salinity increase led to a good acclimation of the
      biomass, as confirmed by the respirometric tests. Significant biofilm detachments
      from carriers were experienced, which contributed to increase the irreversible
      superficial cake deposition. However, this aspect prevented the pore fouling
      tendency in the membrane module of MB-MBR system. On the contrary, the MBR pilot,
      even showing a lower irreversible cake deposition, was characterized by a higher
      pore fouling tendency. 

PMID- 24747384
TI  - Algal-bacterial process for the simultaneous detoxification of thiocyanate
      containing wastewater and maximized lipid production under
      photoautotrophic/photoheterotrophic conditions.
AB  - In this work, a cooperative algal-bacterial system that efficiently degrades
      thiocyanate (SCN(-)), a toxic contaminant, and exhibits high lipid productivity,
      was developed. A consortium of mixed bacteria (activated sludge) and microalgae
      was sequentially cultivated under photoautotrophic and photoheterotrophic modes.
      The hydrolysis of SCN(-) to ammonium (NH4(+))-nitrogen and subsequent
      nitrification steps were performed by the initial activated sludge under
      lithoautotrophic conditions. The NH4(+) and oxidized forms of nitrogen, nitrite
      (NO2(-)) and nitrate (NO3(-)), were then assimilated and removed by the
      microalgal cells when light was supplied. After the degradation of SCN(-), the
      cultivation mode was changed to photoheterotrophic conditions in a sequential
      manner. Algal-bacterial cultures containing Chlorella protothecoides and Ettlia
      sp. yielded significantly increased lipid productivity under photoheterotrophic
      conditions compared to photoautotrophic conditions (28.7- and 17.3-fold higher,
      respectively). Statistical methodologies were also used to investigate the
      effects of volatile fatty acids and yeast extract on biomass and lipid
      production. 

PMID- 24747385
TI  - Reducing NO and N2O emission during aerobic denitrification by newly isolated
      Pseudomonas stutzeri PCN-1.
AB  - As two obligatory intermediates of denitrification, both NO and N2O had harmful
      environmental and biological impacts. An aerobic denitrifying bacterial strain
      PCN-1 was newly isolated and identified as Pseudomonas stutzeri, which was
      capable of high efficient nitrogen removal under aerobic condition with maximal
      NO and N2O accumulation as low as 0.003% and 0.33% of removed NO3(-)-N,
      respectively. Further experiment taking nitrite as denitrifying substrate
      indicated similar low NO and N2O emission of 0.006% and 0.29% of reduced NO2(-)
      N, respectively. Reverse transcription-polymerase chain reaction (RT-PCR)
      analysis revealed that the coordinate expression of denitrification gene nirS
      (for cytochrome cd1 nitrite reductase), cnorB (for NO reductase) and nosZ (for
      N2O reductase) was the fundamental reason of low NO and N2O accumulation.
      Activated sludge system bioaugmented by strain PCN-1 demonstrated a significant
      reduction of NO and N2O emission from wastewater during aerobic denitrification,
      implied great potential of PCN-1 in practical applications. 

PMID- 24747386
TI  - Simultaneous saccharification and fermentation and a consolidated bioprocessing
      for Hinoki cypress and Eucalyptus after fibrillation by steam and subsequent wet
      disk milling.
AB  - An advanced pretreatment method that combines steam treatment (ST) with wet disk
      milling (WDM) was evaluated using two different species of woods, viz., Hinoki
      cypress (softwood) and Eucalyptus (hardwood). Bioconversion of the pretreated
      products was performed using enzymatic saccharification via a commercial
      cellulase mixture and two types of fermentation processing, i.e., yeast-based
      simultaneous saccharification and fermentation (SSF) and Clostridium thermocellum
      based consolidated bioprocessing (CBP). A higher yield of glucose was obtained in
      the enzymatic saccharification and fermentation products from SSF and CBP with
      pretreatment consisting of WDM after ST, as compared to either ST or WDM alone.
      Maximum ethanol production via SSF and CBP were 359.3 and 79.4 mg/g-cellulose
      from Hinoki cypress, and 299.5 and 73.1 mg/g-cellulose from Eucalyptus,
      respectively. While the main fermentation product generated in CBP was acetate,
      the total products yield was 319.9 and 262.0 mg/g-cellulose from Hinoki cypress
      and Eucalyptus, respectively.

PMID- 24747387
TI  - A comparative study of bio-oils from pyrolysis of microalgae and oil seed waste
      in a fluidized bed.
AB  - The pyrolysis of Scenedesmus sp. and Jatropha seedshell cake (JSC) was
      investigated under similar operating condition in a fluidized bed reactor for
      comparison of pyrolytic behaviors from different species of lipids-containing
      biomass. Microalgae showed a narrower main peak in differential thermogravimetric
      curve compared to JSC due to different constituents. Pyrolysis liquid yields were
      similar; liquid's oil proportion of microalgae is higher than JSC. Microalgae bio
      oil was characterized by similar carbon and hydrogen contents and higher H/C and
      O/C molar ratios compared to JSC due to compositional difference. The pyrolytic
      oils from microalgae and JSC contained more oxygen and nitrogen and less sulfur
      than petroleum and palm oils. The pyrolytic oils showed high yields of fatty
      oxygenates and nitrogenous compounds. The microalgae bio-oil features in high
      concentrations of aliphatic compounds, fatty acid alkyl ester, alcohols and
      nitriles. Microalgae showed potentials for alternative feedstock for green
      diesel, and commodity and valuable chemicals. 

PMID- 24747388
TI  - Exploring the links between population dynamics of total and active bacteria and
      the variables influencing a full-scale membrane bioreactor (MBR).
AB  - Long-term dynamics of total and active bacterial populations in a full-scale
      membrane bioreactor (MBR) treating urban wastewater were monitored during nine
      months by temperature-gradient gel electrophoresis (TGGE) of partial 16S-rRNA
      genes, amplified from community DNA and RNA templates. The bacterial community,
      dominated by Alphaproteobacteria, displayed the required characteristics for a
      successful and steady contaminant removal under real operating conditions. The
      evolution of population dynamics showed that a fully-stable microbial community
      was not developed even after technical stabilization and steady performance of
      the MBR were achieved. Non-metric multidimensional scaling and BIO-ENV
      demonstrated that the trends of the populations were often mostly explained by
      temperature, followed by the concentration of volatile suspended solids and C/N
      ratio of the influent. These variables were mainly responsible for triggering the
      shifts between functionally redundant populations. These conclusions contribute
      to the prediction of the complex profiles of adaptation and response of bacterial
      populations under changing conditions. 

PMID- 24747389
TI  - Characterization of Chlorococcum pamirum as a potential biodiesel feedstock.
AB  - To evaluate the potential of Chlorococcum pamirum for producing biodiesel, the
      effects of nitrogen, phosphate, initial cell concentrations and NaCl on lipid
      accumulation and growth were studied. The highest specific growth rate (MU(max)),
      biomass productivity and lipid content achieved was 1.888 d(-1), 350.1 mg L(-1)
      day(-1), and 64.9%, respectively. Under nitrogen-deficient condition, the cells
      accumulated lipids faster at low initial cell concentration. Additional NaCl to
      nitrogen-deficient media accelerated the lipid accumulation. When adding 10 g L(
      1) NaCl to nitrogen-deficient media, the lipid content and productivity of cells
      cultured outdoors with high initial cell concentration increased from 38.2% and
      153 mg L(-1) day(-1) to 54.3% and 192 mg L(-1) day(-1) respectively. Moreover,
      NaCl enhanced the saturated fatty acids content from 56.40% to 73.41% of total
      fatty acids. The results show that C. pamirum is a promising organism for biofuel
      production.

PMID- 24747390
TI  - First steps towards a constructal Microbial Fuel Cell.
AB  - In order to reach real operating conditions with consequent organic charge flow,
      a multi-channel reactor for Microbial Fuel Cells is designed. The feed-through
      double chamber reactor is a two-dimensional system with four parallel channels
      and Reticulated Vitreous Carbon as electrodes. Based on thermodynamical
      calculations, the constructal-inspired distributor is optimized with the aim to
      reduce entropy generation along the distributing path. In the case of negligible
      singular pressure drops, the Hess-Murray law links the lengths and the hydraulic
      diameters of the successive reducing ducts leading to one given working channel.
      The determination of generated entropy in the channels of our constructal MFC is
      based on the global hydraulic resistance caused by both regular and singular
      pressure drops. Polarization, power and Electrochemical Impedance Spectroscopy
      show the robustness and the efficiency of the cell, and therefore the potential
      of the constructal approach. Routes towards improvements are suggested in terms
      of design evolutions. 

PMID- 24747391
TI  - Identification and characterization of a freshwater microalga Scenedesmus SDEC-8
      for nutrient removal and biodiesel production.
AB  - The selection of the right strains is of fundamental important to the success of
      the algae-based oil industry. From the six newly isolated microalgae strains
      tested for growth, fatty acid methyl ester (FAME) profiles and biodiesel
      properties, Scenedesmus SDEC-8, with favorable C16:0 fatty acids (73.43%), showed
      the best combined results. Then, morphological and molecular identification were
      examined. From the three wastewaters samples, Scenedesmus SDEC-8 showed good
      ability to yield oil and remove nutrients, which were comparable with other
      reports. In b artificial wastewater (TN 40 mg L(-1), TP 8 mg L(-1)), Scenedesmus
      SDEC-8 achieved the highest value of lipid productivity (53.84 mg L(-1) d(-1)),
      MUFA content (35.35%) and total FAME content (59.57+/-0.02 mg g(-1) DW), besides
      higher removal efficiencies of TN (99.18%) and TP (98.86%) helped effluent
      directly discharge and smaller dilution factor of N, P (3.3 and 9) which was good
      for lessening water utilization.

PMID- 24747392
TI  - Mechanism on microwave-assisted acidic solvolysis of black-liquor lignin.
AB  - Microwave-assisted degradation of black-liquor lignin with formic acid was
      studied, concerning the product yield and distribution of phenolic compounds
      against reaction temperature (110-180 degrees C) and reaction time (5-90 min).
      The liquid product consisting of bio-oil 1 and bio-oil 2, achieved the maxima
      yield of 64.08% at 160 degrees C and 30 min (bio-oil 1: 9.69% and bio-oil 2:
      54.39%). The chemical information of bio-oil 1 and bio-oil 2 were respectively
      identified by means of Gas Chromatography-Mass Spectrometer (GC-MS) and Matrix
      assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF
      MS), while the solid residue was analyzed by Gel Permeation Chromatography (GPC)
      and Fourier Transform Infrared Spectroscopy (FTIR). A possible mechanism was
      proposed for the microwave-assisted acidic solvolysis of lignin, specifying the
      kinetic relationship among the primary cracking of lignin, repolymerization of
      the oligomers and formation of solid residue.

PMID- 24747393
TI  - Bio-based phenols and fuel production from catalytic microwave pyrolysis of
      lignin by activated carbons.
AB  - The aim of this study is to explore catalytic microwave pyrolysis of lignin for
      renewable phenols and fuels using activated carbon (AC) as a catalyst. A central
      composite experimental design (CCD) was used to optimize the reaction condition.
      The effects of reaction temperature and weight hourly space velocity (WHSV, h(
      1)) on product yields were investigated. GC/MS analysis showed that the main
      chemical compounds of bio-oils were phenols, guaiacols, hydrocarbons and esters,
      most of which were ranged from 71% to 87% of the bio-oils depending on different
      reaction conditions. Bio-oils with high concentrations of phenol (45% in the bio
      oil) were obtained. The calorific value analysis revealed that the high heating
      values (HHV) of the lignin-derived biochars were from 20.4 to 24.5 MJ/kg in
      comparison with raw lignin (19 MJ/kg). The reaction mechanism of this process was
      analyzed.

PMID- 24747394
TI  - Investigating the potential for a self-sustaining slow pyrolysis system under
      varying operating conditions.
AB  - This work aimed to investigate the impact of highest treatment temperature (HTT),
      heating rate, carrier gas flow rate and feedstock on the composition and energy
      content of pyrolysis gas to assess whether a self-sustained system could be
      achieved through the combustion of the gas fraction alone, leaving other co
      products available for alternative high-value uses. Calculations based on gas
      composition showed that the pyrolysis process could be sustained by the energy
      contained within the pyrolysis gases alone. The lower energy limit (6% biomass
      higher heating value (HHV)) was surpassed by pyrolysis at ?450 degrees C while
      only a HTT of 650 degrees C consistently met the upper energy limit (15% biomass
      HHV). These findings fill an important gap in literature related to the energy
      balance of the pyrolysis systems for biochar production, and show that, at least
      from an energy balance perspective; self-sustained slow pyrolysis for co
      production of biochar and liquid products is feasible. 

PMID- 24747395
TI  - Statistical optimization of thermal pretreatment conditions for enhanced
      biomethane production from defatted algal biomass.
AB  - The present study analyzes the effect of thermal pretreatment for enhancing the
      biomethane potential of defatted algal biomass of Scenedesmus dimorphus through
      statistically guided experimental design. To this end, defatted microalgal
      biomass at various concentrations (1, 3 and 5 g L(-1)) was pretreated at elevated
      temperatures (100, 120 and 150 degrees C) for 20, 40 and 60 min. The solubilised
      TOC was favourably enhanced up to 71 mg L(-1) after pretreatment at a temperature
      of 150 degrees C for reaction time of 60 min. The methane yield was substantially
      enhanced (up to 60%) and could be correlated with an increase in organic matter
      solubilisation and enhanced biodegradability via thermal pretreatment. The
      optimisation of the integrated thermal pretreatment-biomethanation process
      resulted in up to 1.6-fold increase in methane yield.

PMID- 24747396
TI  - Hydraulic characterization and optimization of total nitrogen removal in an
      aerated vertical subsurface flow treatment wetland.
AB  - In this study, a side-by-side comparison of two pilot-scale vertical subsurface
      flow constructed wetlands (6.2 m(2)*0.85 m, q(i)=95 L/m(2) d, tau(n)=3.5 d)
      handling primary treated domestic sewage was conducted. One system (VA-i) was set
      to intermittent aeration while the other was aerated continuously (VAp-c).
      Intermittent aeration was provided to VA-i in an 8 h on/4 h off pattern. The
      intermittently aerated wetland, VA-i, was observed to have 70% less nitrate
      nitrogen mass outflow than the continuously aerated wetland, VAp-c. Intermittent
      aeration was shown to increase treatment performance for TN while saving 33% of
      running energy cost for aeration. Parallel tracer experiments in the two wetlands
      showed hydraulic characteristics similar to one Continuously Stirred Tank Reactor
      (CSTR). Intermittent aeration did not significantly affect the hydraulic
      functioning of the system. Hydraulic efficiencies were 78% for VAp-c and 76% for
      VA-i.

PMID- 24747397
TI  - Human health risk assessment of nitrosamines and nitramines for potential
      application in CO2 capture.
AB  - Emission and accumulation of carbon dioxide (CO2) in the atmosphere exert an
      environmental and climate change challenge. An attempt to deal with this
      challenge is made at Mongstad by application of amines for CO2 capture and
      storage (CO2 capture Mongstad (CCM) project). As part of the CO2 capture process,
      nitrosamines and nitramines may be emitted. Toxicological testing of nitrosamines
      and nitramines indicate a genotoxic potential of these substances. Here we
      present a risk characterization and assessment for five nitrosamines (N-Nitrosodi
      methylamine (NDMA) N-Nitrosodi-ethylamine (NDEA), N-Nitroso-morpholine (NNM), N
      Nitroso-piperidine (NPIP), and Dinitroso-piperazine (DNP)) and two nitramines (N
      Methyl-nitramine (NTMA), Dimethyl-nitramine (NDTMA)), which are potentially
      emitted from the CO2 capture plant (CCP). Human health risk assessment of
      genotoxic non-threshold substances is a heavily debated topic, and no consensus
      methodology exists internationally. Extrapolation modeling from high-dose animal
      exposures to low-dose human exposures can be crucial for the final risk
      calculation. In the work presented here, different extrapolation models are
      discussed, and suggestions on applications are given. Then, preferred methods for
      calculating derived minimal effect level (DMEL) are presented with the selected
      nitrosamines and nitramines. 

PMID- 24747398
TI  - Carcinogenicity study of CKD-501, a novel dual peroxisome proliferator-activated
      receptors alpha and gamma agonist, following oral administration to Sprague
      Dawley rats for 94-101 weeks.
AB  - CKD-501 is a peroxisome proliferator-activated receptor (PPAR) agonist. The
      current study was conducted in Sprague Dawley (SD) rats for 94-101 weeks to
      investigate the carcinogenic potential of CKD-501. 60 males received 0, 0.03,
      0.12, or 1.0mg/kg/day, which was changed after 66 weeks to 0.24 mg/kg/day due to
      increased mortality, while 60 females received 0, 0.03, 0.06, or 0.12 mg/kg/day
      throughout the study period. After switching the dosage, no significant changes
      in the survival rates were observed. Non-neoplastic lesions such as bladder
      transitional cell hyperplasia and a diminished corpus luteum were observed in
      females administered 0.12 mg/kg/day and the right chamber dilation and left
      ventricular hypertrophy were increased dose dependently in both males and
      females. Non-neoplastic lesions such as bone marrow hypoplasia and fat cell
      proliferation and neoplastic lesions such as lipomas and liposarcomas observed in
      males and/or females were considered expected pharmacological effects for this
      compound. Compared to rosiglitazone, CKD-501 had a 4.4-fold higher margin of
      safety for tumor induction and did not cause bladder carcinoma as was observed
      with pioglitazone.

PMID- 24747399
TI  - Spontaneous transfer of chirality in an atropisomerically enriched two-axis
      system.
AB  - One of the most well-recognized stereogenic elements in a chiral molecule is an
      sp(3)-hybridized carbon atom that is connected to four different substituents.
      Axes of chirality can also exist about bonds with hindered barriers of rotation;
      molecules containing such axes are known as atropisomers. Understanding the
      dynamics of these systems can be useful, for example, in the design of single
      atropisomer drugs or molecular switches and motors. For molecules that exhibit a
      single axis of chirality, rotation about that axis leads to racemization as the
      system reaches equilibrium. Here we report a two-axis system for which an
      enantioselective reaction produces four stereoisomers (two enantiomeric pairs):
      following a catalytic asymmetric transformation, we observe a kinetically
      controlled product distribution that is perturbed from the system's equilibrium
      position. As the system undergoes isomerization, one of the diastereomeric pairs
      drifts spontaneously to a higher enantiomeric ratio. In a compensatory manner,
      the enantiomeric ratio of the other diastereomeric pair decreases. These
      observations are made for a class of unsymmetrical amides that exhibits two
      asymmetric axes--one axis is defined through a benzamide substructure, and the
      other axis is associated with differentially N,N-disubstituted amides. The
      stereodynamics of these substrates provides an opportunity to observe a curious
      interplay of kinetics and thermodynamics intrinsic to a system of stereoisomers
      that is constrained to a situation of partial equilibrium.

PMID- 24747400
TI  - Dichloroacetate prevents restenosis in preclinical animal models of vessel
      injury.
AB  - Despite the introduction of antiproliferative drug-eluting stents, coronary heart
      disease remains the leading cause of death in the United States. In-stent
      restenosis and bypass graft failure are characterized by excessive smooth muscle
      cell (SMC) proliferation and concomitant myointima formation with luminal
      obliteration. Here we show that during the development of myointimal hyperplasia
      in human arteries, SMCs show hyperpolarization of their mitochondrial membrane
      potential (DeltaPsim) and acquire a temporary state with a high proliferative
      rate and resistance to apoptosis. Pyruvate dehydrogenase kinase isoform 2 (PDK2)
      was identified as a key regulatory protein, and its activation proved necessary
      for relevant myointima formation. Pharmacologic PDK2 blockade with
      dichloroacetate or lentiviral PDK2 knockdown prevented DeltaPsim
      hyperpolarization, facilitated apoptosis and reduced myointima formation in
      injured human mammary and coronary arteries, rat aortas, rabbit iliac arteries
      and swine (pig) coronary arteries. In contrast to several commonly used
      antiproliferative drugs, dichloroacetate did not prevent vessel re
      endothelialization. Targeting myointimal DeltaPsim and alleviating apoptosis
      resistance is a novel strategy for the prevention of proliferative vascular
      diseases. 

PMID- 24747402
TI  - [Surgical aspects of intraductal papillary mucinous neoplasm of the pancreas].
AB  - Intraductal papillary mucinous neoplasms (IPMN) have a distinguished role amongst
      the exocrine pancreatic tumours. Although IPMN is less than 1% of all pancreatic
      neoplasms, cystic tumours, which has got in the spotlight recently, belong to
      this histopathological subtype up to 20% to 30%. IPMN originate from the main-
      and accessory pancreatic ducts. Rate of malignancy, prognosis and, therefore, the
      operative indications can be quite different. Although the prognosis of ductal
      carcinoma developed on the basis of IPMN is similar to classic adenocarcinoma -
      10% 5-year survival - the overall prognosis of IPMN is much more favourable with
      over 70% survival rate in case of non-invasive cancers. Hence, it is important
      the timely diagnosis and surgical resection of IPMN to prevent development of
      invasive cancer. 

PMID- 24747401
TI  - Structure of the AcrAB-TolC multidrug efflux pump.
AB  - The capacity of numerous bacterial species to tolerate antibiotics and other
      toxic compounds arises in part from the activity of energy-dependent
      transporters. In Gram-negative bacteria, many of these transporters form
      multicomponent 'pumps' that span both inner and outer membranes and are driven
      energetically by a primary or secondary transporter component. A model system for
      such a pump is the acridine resistance complex of Escherichia coli. This pump
      assembly comprises the outer-membrane channel TolC, the secondary transporter
      AcrB located in the inner membrane, and the periplasmic AcrA, which bridges these
      two integral membrane proteins. The AcrAB-TolC efflux pump is able to transport
      vectorially a diverse array of compounds with little chemical similarity, thus
      conferring resistance to a broad spectrum of antibiotics. Homologous complexes
      are found in many Gram-negative species, including in animal and plant pathogens.
      Crystal structures are available for the individual components of the pump and
      have provided insights into substrate recognition, energy coupling and the
      transduction of conformational changes associated with the transport process.
      However, how the subunits are organized in the pump, their stoichiometry and the
      details of their interactions are not known. Here we present the pseudo-atomic
      structure of a complete multidrug efflux pump in complex with a modulatory
      protein partner from E. coli. The model defines the quaternary organization of
      the pump, identifies key domain interactions, and suggests a cooperative process
      for channel assembly and opening. These findings illuminate the basis for drug
      resistance in numerous pathogenic bacterial species. 

PMID- 24747403
TI  - [The surgical case of a 34-year-old female patient with a metastatizing double
      colon tumor with different histological structure, causing mechanical
      obstruction].
AB  - We would like to present the case of a young woman (age 34) who was admitted to
      our department due to unbearable colicky pain, which started one week prior to
      her hospitalization. Examinations revealed mechanical obstruction, which is very
      unusual in her age without surgical history. During emergency surgery, we found
      descending colon tumour which was invading the abdominal wall with pelvic
      carcinomatosis at the border of the sigmoid colon. Due to extreme colonic
      dilation and impending rupture of the colonic serosa, we performed a subtotal
      colectomy with ileosigmoid anastomosis. In addition, pelvic peritonectomy was
      carried out, too. The histopathological examination of the resected part
      demonstrated adenocarcinoma of the descending-sigmoid colon, as well as another -
      histologically different - tumour (a well-differentiated neuroendocrine carcinoma
      [NEC]), which would not have been discovered, because it was invisible and
      impalpable. However, this latter tumour was responsible for the peritoneal
      metastases. 

PMID- 24747404
TI  - [Evaluation of patients' satisfaction after breast reconstruction with latissimus
      dorsi myocutaneous flap and immediate permanent breast implant].
AB  - Current surgical treatment modalities for breast reconstruction include
      latissimus dorsi mycotaneous flap with immediate permanent breast implant (LDI).
      The aim of the present study was to analyze reconstruction with LDI in terms of
      quality of life, cosmesis and patient satisfaction. A chart analysis was carried
      out with the first ten patients who underwent breast reconstruction with LDI. The
      patients were interviewed and self-assessment quality of life was administered.
      They also underwent assessment of satisfaction and cosmesis. The high
      satisfaction and cosmesis scores in the breast reconstruction group indicate the
      superior results that can be achieved with breast reconstruction. 

PMID- 24747405
TI  - [To the editors: informed consent in surgery].

PMID- 24747406
TI  - [Professor Gabor Petri was born 100 years ago].

PMID- 24747407
TI  - [Rudolf Kos (1915-2014)].

PMID- 24747408
TI  - [2nd Congress of the Hungarian Association of Young Surgeons, Balatonalmadi,
      April 4-6, 2014 - Report and abstracts].

PMID- 24747409
TI  - [Report from the 15th Congress of the Endoscopy Section of the Hungarian Surgery
      Association, Herceghalom, October 10-12, 2013].

PMID- 24747412
TI  - Effectiveness of periodontal treatment on the improvement of inflammatory markers
      in children.
AB  - AIM: It is known that atherosclerosis begins in childhood, a behaviour towards
      oral health care and metabolic control, since an early age, is essential for
      patients with cardiovascular disease. The aim of this research was to evaluate
      the effectiveness of periodontal treatment full-mouth scaling and root planning
      (FMSRP), applied to children without systemic diseases, correlating with
      periodontal clinical and blood parameters (lipid profile and inflammatory
      markers). MATERIALS AND METHODS: The 29 patients were divided into two groups,
      group 1 (14) - scaling and rot planning (SRP), group 2 (15) - FMSRP and the
      follow-up was conducted among 180 days. RESULTS: The results showed a significant
      improvement in clinical periodontal parameters (p<0.05) in both groups. In the
      analyzed blood parameters there was a greater evidence, with a significant
      improvement (p<0.05), in total cholesterol (TC), triglycerides (TGs), fibrinogen
      (FGN), and interleukin-6 (IL-6) CONCLUSIONS: Thus, we suggest that both
      periodontal treatments were effective in children without any systemic diseases.

PMID- 24747413
TI  - Detection of glycoalkaloids using disposable biosensors based on genetically
      modified enzymes.
AB  - In this work we present a rapid, selective, and highly sensitive detection of
      alpha-solanine and alpha-chaconine using cholinesterase-based sensors. The high
      sensitivity of the devices is brought by the use of a genetically modified
      acetylcholinesterase (AChE), combined with a one-step detection method based on
      the measurement of inhibition slope. The selectivity was obtained by using
      butyrylcholinesterase (BChE), an enzyme able to detect these two toxins with
      differential inhibition kinetics. The enzymes were immobilized via entrapment in
      PVA-AWP polymer directly on the working electrode surface. The analysis of the
      resulting inhibition slope was performed employing linear regression function
      included in Matlab. The high toxicity of alpha-chaconine compared to alpha
      solanine due to a better affinity to the active site was proved. The inhibition
      of glycoalkaloids (GAs) mixture was performed over AChE enzyme wild-type AChE and
      BChE biosensors resulting in the detection of synergism effect. The developed
      method allows the detection of (GAs) at 50 ppb in potato matrix.

PMID- 24747414
TI  - Zamilon, a novel virophage with Mimiviridae host specificity.
AB  - Virophages, which are potentially important ecological regulators, have been
      discovered in association with members of the order Megavirales. Sputnik
      virophages target the Mimiviridae, Mavirus was identified with the Cafeteria
      roenbergensis virus, and virophage genomes reconstructed by metagenomic analyses
      may be associated with the Phycodnaviridae. Despite the fact that the Sputnik
      virophages were isolated with viruses belonging to group A of the Mimiviridae,
      they can grow in amoebae infected by Mimiviridae from groups A, B or C. In this
      study we describe Zamilon, the first virophage isolated with a member of group C
      of the Mimiviridae family. By co-culturing amoebae with purified Zamilon, we
      found that the virophage is able to multiply with members of groups B and C of
      the Mimiviridae family but not with viruses from group A. Zamilon has a 17,276 bp
      DNA genome that potentially encodes 20 genes. Most of these genes are closely
      related to genes from the Sputnik virophage, yet two are more related to
      Megavirus chiliensis genes, a group B Mimiviridae, and one to Moumouvirus monve
      transpoviron. 

PMID- 24747415
TI  - A novel highly potent autotaxin/ENPP2 inhibitor produces prolonged decreases in
      plasma lysophosphatidic acid formation in vivo and regulates urethral tension.
AB  - Autotaxin, also known as ectonucleotide pyrophosphatase/phosphodiesterase 2
      (ENPP2), is a secreted enzyme that has lysophospholipase D activity, which
      converts lysophosphatidylcholine to bioactive lysophosphatidic acid.
      Lysophosphatidic acid activates at least six G-protein coupled recpetors, which
      promote cell proliferation, survival, migration and muscle contraction. These
      physiological effects become dysfunctional in the pathology of cancer, fibrosis,
      and pain. To date, several autotaxin/ENPP2 inhibitors have been reported;
      however, none were able to completely and continuously inhibit autotaxin/ENPP2 in
      vivo. In this study, we report the discovery of a highly potent autotaxin/ENPP2
      inhibitor, ONO-8430506, which decreased plasma lysophosphatidic acid formation.
      The IC50 values of ONO-8540506 for lysophospholipase D activity were 6.4-19 nM
      for recombinant autotaxin/ENPP2 proteins and 4.7-11.6 nM for plasma from various
      animal species. Plasma lysophosphatidic acid formation during 1-h incubation was
      almost completely inhibited by the addition of >300 nM of the compound to human
      plasma. In addition, when administered orally to rats at a dose of 30 mg/kg, the
      compound demonstrated good pharmacokinetics in rats and persistently inhibited
      plasma lysophosphatidic acid formation even at 24 h after administration. Smooth
      muscle contraction is a known to be promoted by lysophosphatidic acid. In this
      study, we showed that dosing rats with ONO-8430506 decreased intraurethral
      pressure accompanied by urethral relaxation. These findings demonstrate the
      potential of this autotaxin/ENPP2 inhibitor for the treatment of various diseases
      caused by lysophosphatidic acid, including urethral obstructive disease such as
      benign prostatic hyperplasia. 

PMID- 24747416
TI  - Sequential decisions: a computational comparison of observational and
      reinforcement accounts.
AB  - Right brain damaged patients show impairments in sequential decision making tasks
      for which healthy people do not show any difficulty. We hypothesized that this
      difficulty could be due to the failure of right brain damage patients to develop
      well-matched models of the world. Our motivation is the idea that to navigate
      uncertainty, humans use models of the world to direct the decisions they make
      when interacting with their environment. The better the model is, the better
      their decisions are. To explore the model building and updating process in humans
      and the basis for impairment after brain injury, we used a computational model of
      non-stationary sequence learning. RELPH (Reinforcement and Entropy Learned Pruned
      Hypothesis space) was able to qualitatively and quantitatively reproduce the
      results of left and right brain damaged patient groups and healthy controls
      playing a sequential version of Rock, Paper, Scissors. Our results suggests that,
      in general, humans employ a sub-optimal reinforcement based learning method
      rather than an objectively better statistical learning approach, and that
      differences between right brain damaged and healthy control groups can be
      explained by different exploration policies, rather than qualitatively different
      learning mechanisms. 

PMID- 24747417
TI  - The optimal solution of a non-convex state-dependent LQR problem and its
      applications.
AB  - This paper studies a Non-convex State-dependent Linear Quadratic Regulator
      (NSLQR) problem, in which the control penalty weighting matrix [Formula: see
      text] in the performance index is state-dependent. A necessary and sufficient
      condition for the optimal solution is established with a rigorous proof by Euler
      Lagrange Equation. It is found that the optimal solution of the NSLQR problem can
      be obtained by solving a Pseudo-Differential-Riccati-Equation (PDRE)
      simultaneously with the closed-loop system equation. A Comparison Theorem for the
      PDRE is given to facilitate solution methods for the PDRE. A linear time-variant
      system is employed as an example in simulation to verify the proposed optimal
      solution. As a non-trivial application, a goal pursuit process in psychology is
      modeled as a NSLQR problem and two typical goal pursuit behaviors found in human
      and animals are reproduced using different control weighting [Formula: see text].
      It is found that these two behaviors save control energy and cause less stress
      over Conventional Control Behavior typified by the LQR control with a constant
      control weighting [Formula: see text], in situations where only the goal
      discrepancy at the terminal time is of concern, such as in Marathon races and
      target hitting missions. 

PMID- 24747419
TI  - A three step network based approach (TSNBA) to finding disease molecular
      signature and key regulators: a case study of IL-1 and TNF-alpha stimulated
      inflammation.
AB  - A disease molecular signature is a set of biomolecular features that are
      prognostic of clinical phenotypes and indicative of underlying pathology. It is
      of great importance to develop computational approaches for finding more relevant
      molecular signatures. Based upon the hypothesis that various components in a
      molecular signature are more likely to share similar patterns, we introduced a
      novel three step network based approach (TSNBA) to identify the molecular
      signature and key pathological regulators. Protein-protein interaction (PPI)
      network and ranking algorithm were integrated in the first step to find pathology
      related proteins with high accuracy. It was followed by the second step to
      further screen with co-expression patterns for better pathology enrichment.
      Context likelihood of relatedness (CLR) algorithm was used in the third step to
      infer gene regulatory networks and identify key transcription regulators. We
      applied this approach to study IL-1 (interleukin-1) and TNF-alpha (tumor necrosis
      factor-alpha) stimulated inflammation. TSNBA identified inflammatory signature
      with high accuracy and outperformed 5 competing methods namely fold change,
      degree, interconnectivity, neighborhood score and network propagation based
      approaches. The best molecular signature, with 80% (40/50) confirmed inflammatory
      genes, was used to predict inflammation related genes. As a result, 8 out of 10
      predicted inflammation genes that were not included in the benchmark Entrez Gene
      database were validated by literature evidence. Furthermore, 23 of the 32
      predicted inflammation regulators were validated by literature evidence. The rest
      9 were also validated with TF (transcription factor) binding site analysis. In
      conclusion, we developed an efficient strategy for disease molecular signature
      finding and key pathological regulator identification. 

PMID- 24747420
TI  - Risk of stroke and intracranial hemorrhage in 9727 Chinese with atrial
      fibrillation in Hong Kong.
AB  - BACKGROUND: Current risk schemes to predict ischemic stroke and intracranial
      hemorrhage (ICH) in atrial fibrillation (AF) are derived primarily using a
      Caucasian population. OBJECTIVE: The purpose of this study was to describe the
      risk of ischemic stroke and ICH in a large contemporary "real world" cohort of
      Chinese AF patients in Hong Kong with detailed long-term follow-up. METHODS: This
      observational study used a hospital-based cohort of Chinese patients with
      nonvalvular AF. RESULTS: Among 9727 patients with nonvalvular AF (age 76.9 +/-
      12.5 years, 52.1% female), 3881 patients (39.9%) did not receive antithrombotic
      therapy, 3934 patients (40.4%) were taking aspirin, and 1912 (19.7%) were taking
      warfarin. After mean follow-up of 3.19 years, 847 patients (21.8%) without
      antithrombotic therapy developed ischemic strokes (annual risk 9.28%, 95%
      confidence interval [CI] 8.89%-9.70%). There was a progressively increase in
      annual risk of ischemic stroke with increasing CHADS2 and CHA2DS2VASc scores. The
      c-statistics revealed that CHA2DS2-VASc scores (0.525, 95% CI 0.509-0.541, P =
      .017) was better than CHADS2 scores (0.506, 95% CI 0.490-0.522, P = .584) in
      predicting ischemic stroke. Use of aspirin and of warfarin were associated with
      reduced annual risk of ischemic stroke by 18.7% and 52.7%, respectively (P <.05).
      The annual incidence of ICH in patients taking aspirin and warfarin was 0.77% per
      year and 0.80% per year, respectively. The adjusted net clinical benefit favored
      warfarin over aspirin or no therapy for almost all Chinese AF patients CHA2DS2
      VASc score >=1. CONCLUSION: Chinese AF patients are at high risk for ischemic
      stroke. Analysis of the net clinical benefit favors the use of warfarin over
      aspirin or no therapy for stroke prevention in a broad range of Chinese AF
      patients.

PMID- 24747418
TI  - Microarray analysis of cell cycle gene expression in adult human corneal
      endothelial cells.
AB  - Corneal endothelial cells (ECs) form a monolayer that controls the hydration of
      the cornea and thus its transparency. Their almost nil proliferative status in
      humans is responsible, in several frequent diseases, for cell pool attrition that
      leads to irreversible corneal clouding. To screen for candidate genes involved in
      cell cycle arrest, we studied human ECs subjected to various environments thought
      to induce different proliferative profiles compared to ECs in vivo. Donor corneas
      (a few hours after death), organ-cultured (OC) corneas, in vitro confluent and
      non-confluent primary cultures, and an immortalized EC line were compared to
      healthy ECs retrieved in the first minutes of corneal grafts. Transcriptional
      profiles were compared using a cDNA array of 112 key genes of the cell cycle and
      analysed using Gene Ontology classification; cluster analysis and gene map
      presentation of the cell cycle regulation pathway were performed by GenMAPP.
      Results were validated using qRT-PCR on 11 selected genes. We found several
      transcripts of proteins implicated in cell cycle arrest and not previously
      reported in human ECs. Early G1-phase arrest effectors and multiple DNA damage
      induced cell cycle arrest-associated transcripts were found in vivo and over
      represented in OC and in vitro ECs. Though highly proliferative, immortalized ECs
      also exhibited overexpression of transcripts implicated in cell cycle arrest.
      These new effectors likely explain the stress-induced premature senescence that
      characterizes human adult ECs. They are potential targets for triggering and
      controlling EC proliferation with a view to increasing the cell pool of stored
      corneas or facilitating mass EC culture for bioengineered endothelial grafts. 

PMID- 24747421
TI  - Noninvasive identification of epicardial ventricular tachycardia substrate by
      magnetic resonance-based signal intensity mapping.
AB  - BACKGROUND: Endo-epicardial substrate ablation reduces ventricular tachycardia
      (VT) recurrences; however, not all patients in whom the epicardium is explored
      have a VT substrate. Contrast-enhanced magnetic resonance imaging (ceMRI) is used
      to characterize VT substrate after myocardial infarction. OBJECTIVE: The purpose
      of this study was to determine if epicardial VT substrate can be identified
      noninvasively by ceMRI-based endo-epicardial signal intensity (SI) mapping.
      METHODS: Myocardial infarction was induced in 31 pigs. Four or 16 weeks later,
      ceMRI was obtained, and the averaged subendocardial and subepicardial SIs were
      projected onto 3-dimensional endocardial and epicardial shells in which dense
      scar, heterogeneous tissue (HT), and normal tissue were differentiated. An HT
      channel was defined as a corridor of HT surrounded by dense scar and connected to
      normal tissue. A "patchy" scar pattern was defined as the presence of at least 3
      dense scar islets surrounded by HT forming >=2 HT channels. Electrophysiologic
      study was performed after ceMRI. RESULTS: Thirty-three different sustained
      monomorphic VTs (291 +/- 49 ms) were induced in 25 pigs. Mid-diastolic
      electrograms were recorded in the endocardium (endocardial VT) in 17 and in the
      epicardium (epicardial VT) in 13. Epicardial SI mapping showed that scar area was
      similar in animals with and without epicardial VT (24 +/- 6 cm2 vs. 25 +/- 12
      cm2), but HT covered a higher surface of the epicardial scar in animals with VT
      (76 +/- 6% vs. 61 +/- 10%, P = .03). A patchy scar pattern was observed in all
      animals with epicardial VT but only in 3 animals without VT (P < .001).
      CONCLUSION: CeMRI-based SI mapping allows identification of the epicardial VT
      substrate.

PMID- 24747422
TI  - Force spectroscopy studies on protein-ligand interactions: a single protein
      mechanics perspective.
AB  - Protein-ligand interactions are ubiquitous and play important roles in almost
      every biological process. The direct elucidation of the thermodynamic, structural
      and functional consequences of protein-ligand interactions is thus of critical
      importance to decipher the mechanism underlying these biological processes. A
      toolbox containing a variety of powerful techniques has been developed to
      quantitatively study protein-ligand interactions in vitro as well as in living
      systems. The development of atomic force microscopy-based single molecule force
      spectroscopy techniques has expanded this toolbox and made it possible to
      directly probe the mechanical consequence of ligand binding on proteins. Many
      recent experiments have revealed how ligand binding affects the mechanical
      stability and mechanical unfolding dynamics of proteins, and provided mechanistic
      understanding on these effects. The enhancement effect of mechanical stability by
      ligand binding has been used to help tune the mechanical stability of proteins in
      a rational manner and develop novel functional binding assays for protein-ligand
      interactions. Single molecule force spectroscopy studies have started to shed new
      lights on the structural and functional consequence of ligand binding on proteins
      that bear force under their biological settings. 

PMID- 24747423
TI  - p53 and ribosome biogenesis stress: the essentials.
AB  - Cell proliferation and cell growth are two tightly linked processes, as the
      proliferation program cannot be executed without proper accumulation of cell
      mass, otherwise endangering the fate of the two daughter cells. It is therefore
      not surprising that ribosome biogenesis, a key element in cell growth, is
      regulated by many cell cycle regulators. This regulation is exerted
      transcriptionally and post-transcriptionally, in conjunction with numerous
      intrinsic and extrinsic signals. Those signals eventually converge at the
      nucleolus, the cellular compartment that is not only responsible for executing
      the ribosome biogenesis program, but also serves as a regulatory hub, responsible
      for integrating and transmitting multiple stress signals to the omnipotent cell
      fate gatekeeper, p53. In this review we discuss when, how and why p53 is
      activated upon ribosomal biogenesis stress, and how perturbation of this critical
      regulatory interplay may impact human disease. 

PMID- 24747424
TI  - Pyruvate kinase M2 and cancer: an updated assessment.
AB  - Cancer cells are characterized by high glycolytic rates to support energy
      regeneration and anabolic metabolism, along with the expression of pyruvate
      kinase isoenzyme M2 (PKM2). The latter catalyzes the last step of glycolysis and
      reprograms the glycolytic flux to feed the special metabolic demands of
      proliferating cells. Besides, PKM2 has moonlight functions, such as gene
      transcription, favoring cancer. Accumulating evidence suggests a critical role
      played by the low-activity-dimeric PKM2 in tumor progression, supported by the
      identification of mutations which result in the down-regulation of its activity
      and tumorigenesis in a nude mouse model. This review discusses PKM2 regulation
      and the benefits it confers to cancer cells. Further, conflicting views on PKM2's
      role in cancer, its therapeutic relevance and future directions in the field are
      also discussed. 

PMID- 24747425
TI  - The X-ray crystal structure of Shewanella oneidensis OmcA reveals new insight at
      the microbe-mineral interface.
AB  - The X-ray crystal structure of Shewanella oneidensis OmcA, an extracellular
      decaheme cytochrome involved in mineral reduction, was solved to a resolution of
      2.7 A. The four OmcA molecules in the asymmetric unit are arranged so the minimum
      distance between heme 5 on adjacent OmcA monomers is 9 A, indicative of a
      transient OmcA dimer capable of intermolecular electron transfer. A previously
      identified hematite binding motif was identified near heme 10, forming a
      hydroxylated surface that would bring a heme 10 electron egress site to ~10 A of
      a mineral surface.

PMID- 24747426
TI  - YAP/TAZ as mechanosensors and mechanotransducers in regulating organ size and
      tumor growth.
AB  - Organ size is controlled by the concerted action of biochemical and physical
      processes. Although mechanical forces are known to regulate cell and tissue
      behavior, as well as organogenesis, the precise molecular events that integrate
      mechanical and biochemical signals to control these processes are not fully
      known. The recently delineated Hippo-tumor suppressor network and its two nuclear
      effectors, YAP and TAZ, shed light on these mechanisms. YAP and TAZ are proto
      oncogene proteins that respond to complex physical milieu represented by the
      rigidity of the extracellular matrix, cell geometry, cell density, cell polarity
      and the status of the actin cytoskeleton. Here, we review the current knowledge
      of how YAP and TAZ function as mechanosensors and mechanotransducers. We also
      suggest that by deciphering the mechanical and biochemical signals controlling
      YAP/TAZ function, we will gain insights into new strategies for cancer treatment
      and organ regeneration. 

PMID- 24747427
TI  - Association of serum phosphorus variability with coronary artery calcification
      among hemodialysis patients.
AB  - Coronary artery calcification (CAC) is associated with increased mortality in
      patients on maintenance hemodialysis (MHD), but the pathogenesis of this
      condition is not well understood. We evaluated the relationship of CAC score
      (CACs) and variability in serum phosphorus in MHD patients. Seventy-seven adults
      on MHD at Huashan Hospital (Shanghai) were enrolled in July, 2010. CAC of all the
      patients were measured by computed tomography and CACs was calculated by the
      Agatston method at the entry of enrollment. Patients were divided into three
      categories according to their CACs (0~10, 11~400, and >400). Blood chemistry was
      recorded every 3 months from January 2008 to July 2010. Phosphorus variation was
      defined by the standard deviation (SD) or coefficient of variation (CV) and it
      was calculated from the past records. The ordinal multivariate logistic
      regression analysis was used to analyze the predictors of CAC. The mean patient
      age (+/- SD) was 61.7 years (+/-11.3) and 51% of patients were men. The mean CACs
      was 609.6 (+/-1062.9), the median CACs was 168.5, and 78% of patients had CACs
      more than 0. Multivariate analysis indicated that female gender (OR = 0.20, 95%
      CI = 0.07-0.55), age (OR = 2.31, 95% CI = 1.32-4.04), serum fibroblast growth
      factor 23 (OR = 2.25, 95% CI = 1.31-3.85), SD-phosphorus calculated from the most
      recent 6 measurements (OR = 2.12; 95% CI = 1.23-3.63), and CV-phosphorus
      calculated from the most recent 6 measurements (OR = 1.90, 95% CI = 1.16-3.11)
      were significantly and independently associated with CACs. These associations
      persisted for phosphorus variation calculated from past 7, 8, 9, 10, and 11
      follow-up values. Variability of serum phosphorus may contribute significantly to
      CAC and keeping serum phosphorus stable may decrease coronary calcification and
      associated morbidity and mortality in MHD patients. 

PMID- 24747428
TI  - Various blood glucose parameters that indicate hyperglycemia after intravenous
      thrombolysis in acute ischemic stroke could predict worse outcome.
AB  - BACKGROUND: Hyperglycemia is common after stroke, and it is well known to worsen
      its outcome. However, it is important to consider that blood glucose (BG) levels
      can undergo dynamic changes during the acute stage of ischemic stroke. We sought
      to investigate the clinical significance of various glucose parameters within
      first 24 hours in acute ischemic stroke (AIS). The study focused on hyperacute
      stage patients who underwent IVT and investigated which parameters of glucose
      demonstrated to be helpful for predicting outcome. METHODS: This was a
      retrospective study of consecutive patients with AIS at a single stroke center.
      Patients were consecutively enrolled if they were treated with IV-tPA within 3
      hours of symptom onset. BG was measured immediately upon arrival in ER, after IVT
      and every 6-8 hours during the first 24 hours after IVT. The various parameters
      of BG were the following: BG before IVT, BG after IVT, mean BG (mBG), maximal BG
      (max BG), standard deviation of BG (sdBG), and standard deviation of mean BG
      (sdmBG). RESULTS: 207 patients (127 men and 80 women) were included in this
      study. Seventy seven of 207 patients had favorable outcomes at 3 months. High BG
      after IVT, mBG and max BG were independently associated with mRS>2 at 3 months
      (adjusted by age, NIHSS, and atrial fibrillation). Several parameters of BG were
      also independently associated with early mortality within 3 months (BG after IVT,
      mBG, and max BG). BG after IVT and mBG over 180 mg/dL were independently
      associated with early mortality within 3 months. CONCLUSION: Serial measurements
      of BG might be a better predictor of clinical outcome in patients with AIS
      treated with IVT than single BG measurements before IVT. Therefore, these results
      suggest that variable parameters of BG could be important for the prediction of
      clinical outcome in AIS treated with IVT.

PMID- 24747430
TI  - Granulocytes of the red claw crayfish Cherax quadricarinatus can endocytose
      beads, E. coli and WSSV, but in different ways.
AB  - The hemocytes of the red claw crayfish Cherax quadricarinatus are classified by
      morphologic observation into the following types: hyalinocytes (H), semi
      granulocytes (SG) and granulocytes (G). Density gradient centrifugation with
      Percoll was developed to separate these three subpopulations of hemocytes. Beads,
      Escherichia coli, and FITC labeling WSSV were used to investigate the
      characteristics of granulocytes by using scanning electron microscope,
      transmission electron microscope, and laser scan confocal microscope. Results
      showed that granulocytes could phagocytose beads and E. coli by endocytic
      pathways. WSSV could rely on caveolae-mediated endocytosis to mainly enter into
      granulocytes. These results could elucidate the mechanism of the innate immunity
      function of granulocytes, and it also showed the mechanism by which WSSV invaded
      granulocytes in the red claw crayfish. 

PMID- 24747429
TI  - Prediagnostic serum biomarkers as early detection tools for pancreatic cancer in
      a large prospective cohort study.
AB  - BACKGROUND: The clinical management of pancreatic cancer is severely hampered by
      the absence of effective screening tools. METHODS: Sixty-seven biomarkers were
      evaluated in prediagnostic sera obtained from cases of pancreatic cancer enrolled
      in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO).
      RESULTS: The panel of CA 19-9, OPN, and OPG, identified in a prior retrospective
      study, was not effective. CA 19-9, CEA, NSE, bHCG, CEACAM1 and PRL were
      significantly altered in sera obtained from cases greater than 1 year prior to
      diagnosis. Levels of CA 19-9, CA 125, CEA, PRL, and IL-8 were negatively
      associated with time to diagnosis. A training/validation study using alternate
      halves of the PLCO set failed to identify a biomarker panel with significantly
      improved performance over CA 19-9 alone. When the entire PLCO set was used for
      training at a specificity (SP) of 95%, a panel of CA 19-9, CEA, and Cyfra 21-1
      provided significantly elevated sensitivity (SN) levels of 32.4% and 29.7% in
      samples collected <1 and >1 year prior to diagnosis, respectively, compared to SN
      levels of 25.7% and 17.2% for CA 19-9 alone. CONCLUSIONS: Most biomarkers
      identified in previously conducted case/control studies are ineffective in
      prediagnostic samples, however several biomarkers were identified as
      significantly altered up to 35 months prior to diagnosis. Two newly derived
      biomarker combinations offered advantage over CA 19-9 alone in terms of SN,
      particularly in samples collected >1 year prior to diagnosis. However, the
      efficacy of biomarker-based tools remains limited at present. Several biomarkers
      demonstrated significant velocity related to time to diagnosis, an observation
      which may offer considerable potential for enhancements in early detection.

PMID- 24747431
TI  - Defensin from the ornate sheep tick Dermacentor marginatus and its effect on Lyme
      borreliosis spirochetes.
AB  - Expression of the previously reported defensin of the tick Dermacentor marginatus
      (defDM) was analysed in different organs by RT-PCR. mRNA of the defDM gene was
      detected in the hemolymph, midgut and salivary glands. Moreover defDM was
      isolated from the tick hemolymph using RP-HPLC and its sequence was determined by
      mass spectrometry and Edman degradation. Synthetic peptide was used for
      determining biological activities. The results showed an anti-Gram-positive
      bacterial role for the defensin. As D. marginatus ticks appear not to be vectors
      of the Lyme disease agent of the complex Borrelia burgdorferi sensu lato, we
      tested the influence of defDM on Borrelia afzelii. There is a very clear
      borrelicidal activity of the defensin, which is concentration dependent and
      suggests a possible role in the clearing of Borrelia ingested by D. marginatus
      ticks.

PMID- 24747432
TI  - A new approach to detect congestive heart failure using short-term heart rate
      variability measures.
AB  - Heart rate variability (HRV) analysis has quantified the functioning of the
      autonomic regulation of the heart and heart's ability to respond. However,
      majority of studies on HRV report several differences between patients with
      congestive heart failure (CHF) and healthy subjects, such as time-domain,
      frequency domain and nonlinear HRV measures. In the paper, we mainly presented a
      new approach to detect congestive heart failure (CHF) based on combination
      support vector machine (SVM) and three nonstandard heart rate variability (HRV)
      measures (e.g. SUM_TD, SUM_FD and SUM_IE). The CHF classification model was
      presented by using SVM classifier with the combination SUM_TD and SUM_FD. In the
      analysis performed, we found that the CHF classification algorithm could obtain
      the best performance with the CHF classification accuracy, sensitivity and
      specificity of 100%, 100%, 100%, respectively. 

PMID- 24747433
TI  - Pathological changes in the COPD lung mesenchyme--novel lessons learned from in
      vitro and in vivo studies.
AB  - Chronic obstructive pulmonary disease (COPD) is currently the fourth leading
      cause of death worldwide and, in contrast to the trend for cardiovascular
      diseases, mortality rates still continue to climb. This increase is in part due
      to an aging population, being expanded by the "Baby boomer" generation who grew
      up when smoking rates were at their peak and by people in developing countries
      living longer. Sadly, there has been a disheartening lack of new therapeutic
      approaches to counteract the progressive decline in lung function associated with
      the disease that leads to disability and death. COPD is characterized by
      irreversible chronic airflow limitation that is caused by emphysematous
      destruction of lung elastic tissue and/or obstruction in the small airways due to
      occlusion of their lumen by inflammatory mucus exudates, narrowing and
      obliteration. These lesions are mainly produced by the response of the tissue to
      the repetitive inhalational injury inflicted by noxious gases, including
      cigarette smoke, which involves interaction between infiltrating inflammatory
      immune cells, resident cells (e.g. epithelial cells and fibroblasts) and the
      extra cellular matrix. This interaction leads to tissue destruction and airway
      remodeling with changes in elastin and collagen, such that the epithelial
      mesenchymal trophic unit is dysregulated in both the disease pathologies. This
      review focuses on: 1--novel inflammatory and remodeling factors that are altered
      in COPD; 2--in vitro and in vivo models to understand the mechanism whereby the
      extra cellular matrix environment in altered in COPD; and 3--COPD in the context
      of wound-repair tissue responses, with a focus on the regulation of mesenchymal
      cell fate and phenotype.

PMID- 24747434
TI  - Evaluation of bendamustine in combination with fludarabine in primary chronic
      lymphocytic leukemia cells.
AB  - The fludarabine and cyclophosphamide couplet has become the backbone of the
      chronic lymphocytic leukemia (CLL) standard of care. Although this is an
      effective treatment, it results in untoward toxicity. Bendamustine is a newly
      approved and better-tolerated alkylating agent. We hypothesized that similar to
      cyclophosphamide, bendamustine-induced DNA damage will be inhibited by
      fludarabine, resulting in increased cytotoxicity. To test this hypothesis and the
      role of the stromal microenvironment in this process, we treated CLL lymphocytes
      in vitro with each drug alone and in combination. Simultaneous or prior addition
      of fludarabine to bendamustine resulted in maximum cytotoxicity assayed by 3,3'
      dihexyloxacarbocyanine iodine negativity, annexin positivity, and poly (adenosine
      5'-diphosphate-ribose) polymerase cleavage. Cytotoxicity elicited by combination
      of both agents was similar in these malignant B cells cultured either in
      suspension or on marrow stroma cells. Cell death was associated with DNA damage
      response, which was determined by phosphorylation of H2AX and unscheduled DNA
      synthesis. H2AX activation was maximum with the drug combination, and unscheduled
      DNA synthesis induced by bendamustine was blocked by fludarabine. In parallel,
      ATM, Chk2, and p53 were phosphorylated and PUMA was induced. Cell death was
      caspase independent; however, caspases did decrease levels of Mcl-1 survival
      protein. These data provide a rationale for combining fludarabine with
      bendamustine for patients with CLL. 

PMID- 24747435
TI  - SATB1 overexpression promotes malignant T-cell proliferation in cutaneous CD30+
      lymphoproliferative disease by repressing p21.
AB  - Cutaneous CD30(+) lymphoproliferative disease (CD30(+)LPD), characterized by the
      presence of CD30(+) anaplastic large T cells, comprises the second most common
      group of cutaneous T-cell lymphoma (CTCL). However, little is known about the
      pathobiology of the CD30(+) lymphoma cells, as well as the mechanisms of disease
      progression. Here we report that Special AT-rich region binding protein 1
      (SATB1), a thymocyte specific chromatin organizer, is over-expressed in CD30(+)
      lymphoma cells in most CD30(+)LPDs, and its expression is upregulated during
      disease progression. Our findings show that SATB1 silencing in CD30(+)LPD cells
      leads to G1 cell cycle arrest mediated by p21 activation. Using chromatin
      immunoprecipitation, luciferase assays, and mutational analysis, we demonstrate
      that SATB1 directly regulates the transcription of p21 in a p53-independent
      manner. Moreover, DNA demethylation on a specific CpG-rich region of the SATB1
      promoter is associated with the upregulation of SATB1 during disease progression.
      These experiments define a novel SATB1-p21 pathway in malignant CD30(+) T
      lymphocytes, which provides novel molecular insights into the pathogenesis of
      CD30(+)LPDs and possibly leads to new therapies. 

PMID- 24747436
TI  - Experimental prestorage filtration removes antibodies and decreases lipids in RBC
      supernatants mitigating TRALI in vivo.
AB  - Transfusion-related acute lung injury (TRALI) remains a significant cause of
      transfusion-related mortality with red cell transfusion. We hypothesize that
      prestorage filtration may reduce proinflammatory activity in the red blood cell
      (RBC) supernatant and prevent TRALI. Filters were manufactured for both small
      volumes and RBC units. Plasma containing antibodies to human lymphocyte antigen
      (HLA)-A2 or human neutrophil antigen (HNA)-3a was filtered, and immunoglobulins
      and specific HNA-3a and HLA-2a neutrophil (PMN) priming activity were measured.
      Antibodies to OX27 were added to plasma, and filtration was evaluated in a 2
      event animal model of TRALI. RBC units from 31 donors known to have antibodies
      against HLA antigens and from 16 antibody-negative controls were filtered.
      Furthermore, 4 RBC units were drawn and underwent standard leukoreduction.
      Immunoglobulins, HLA antibodies, PMN priming activity, and the ability to induce
      TRALI in an animal model were measured. Small-volume filtration of plasma removed
      >96% of IgG, antibodies to HLA-A2 and HNA-3a, and their respective priming
      activity, as well as mitigating antibody-mediated in vivo TRALI. In RBC units,
      experimental filtration removed antibodies to HLA antigens and inhibited the
      accumulation of lipid priming activity and lipid-mediated TRALI. We conclude that
      filtration removes proinflammatory activity and the ability to induce TRALI from
      RBCs and may represent a TRALI mitigation step. 

PMID- 24747437
TI  - Structural validity of the tonic immobility scale in a population exposed to
      trauma: evidence from two large Brazilian samples.
AB  - BACKGROUND: Tonic Immobility is a temporary state of motor inhibition in
      situations involving extreme fear. The first scale developed for its assessment
      was the 10-item Tonic Immobility Scale (TIS). However, there are still few
      studies on its structural (dimensional) validity. The objective of this study was
      to reassess the factor structure of the TIS applied to representative samples
      exposed to general trauma of two Brazilian mega-cities. METHODS: The sample
      comprised 3,223 participants reporting at least one traumatic experience. In Sao
      Paulo (n = 2,148), a Confirmatory Factor Analysis (CFA) first tested the
      originally proposed two-dimensional structure. This was followed by sequential
      Exploratory Structural Equation Models to identify the best fitting model, and
      subsequently tested in Rio de Janeiro (n = 1,075) via CFA. Alternative reduced
      versions were further explored using the aggregate sample. Model-based Item
      Response Theory (IRT) location parameters were also investigated. RESULTS: An
      absence of factor-based convergent and discriminant validity rejected the
      original proposition. However, the one-dimensional structure still held several
      residual correlations. Further exploration indicated the sustainability of
      reduced versions with seven (alternative A) and six (alternative B) items. Both
      presented excellent fit and no relevant residual item correlation. According to
      the IRT location parameters, items in alternative B covered a wider range of the
      latent trait. The Loevinger's H scalability coefficients underscored this
      pattern. CONCLUSIONS: The original model did not hold. A one-factor solution was
      the most tenable in both large samples, but with significant item residual
      correlations, indicating that content redundancies persisted. Further reduced and
      simplified versions of the TIS proved promising. Although studies are yet to be
      carried out in other settings, it is the authors' impression that the restricted
      versions of the TIS are already apt for use in epidemiologic studies since the
      pros tend to outweigh the cons (as outlined in the Discussion section).

PMID- 24747438
TI  - Lipidation of the LC3/GABARAP family of autophagy proteins relies on a membrane
      curvature-sensing domain in Atg3.
AB  - The components supporting autophagosome growth on the cup-like isolation membrane
      are likely to be different from those found on closed and maturing
      autophagosomes. The highly curved rim of the cup may serve as a functionally
      required surface for transiently associated components of the early acting
      autophagic machinery. Here we demonstrate that the E2-like enzyme, Atg3,
      facilitates LC3/GABARAP lipidation only on membranes exhibiting local lipid
      packing defects. This activity requires an amino-terminal amphipathic helix
      similar to motifs found on proteins targeting highly curved intracellular
      membranes. By tuning the hydrophobicity of this motif, we can promote or inhibit
      lipidation in vitro and in rescue experiments in Atg3-knockout cells, implying a
      physiologic role for this stress detection. The need for extensive lipid-packing
      defects suggests that Atg3 is designed to work at highly curved membranes,
      perhaps including the limiting edge of the growing phagophore. 

PMID- 24747439
TI  - Cellular origin of bladder neoplasia and tissue dynamics of its progression to
      invasive carcinoma.
AB  - Understanding how malignancies arise within normal tissues requires
      identification of the cancer cell of origin and knowledge of the cellular and
      tissue dynamics of tumour progression. Here we examine bladder cancer in a
      chemical carcinogenesis model that mimics muscle-invasive human bladder cancer.
      With no prior bias regarding genetic pathways or cell types, we prospectively
      mark or ablate cells to show that muscle-invasive bladder carcinomas arise
      exclusively from Sonic hedgehog (Shh)-expressing stem cells in basal urothelium.
      These carcinomas arise clonally from a single cell whose progeny aggressively
      colonize a major portion of the urothelium to generate a lesion with histological
      features identical to human carcinoma in situ. Shh-expressing basal cells within
      this precursor lesion become tumour-initiating cells, although Shh expression is
      lost in subsequent carcinomas. We thus find that invasive carcinoma is initiated
      from basal urothelial stem cells but that tumour cell phenotype can diverge
      significantly from that of the cancer cell of origin. 

PMID- 24747440
TI  - Profilin-1 phosphorylation directs angiocrine expression and glioblastoma
      progression through HIF-1alpha accumulation.
AB  - The tumour vascular microenvironment supports tumorigenesis not only by supplying
      oxygen and diffusible nutrients but also by secreting soluble factors that
      promote tumorigenesis. Here we identify a feedforward mechanism in which
      endothelial cells (ECs), in response to tumour-derived mediators, release
      angiocrines driving aberrant vascularization and glioblastoma multiforme (GBM)
      progression through a hypoxia-independent induction of hypoxia-inducible factor
      (HIF)-1alpha. Phosphorylation of profilin-1 (Pfn-1) at Tyr 129 in ECs induces
      binding to the tumour suppressor protein von Hippel-Lindau (VHL), and prevents
      VHL-mediated degradation of prolyl-hydroxylated HIF-1alpha, culminating in HIF
      1alpha accumulation even in normoxia. Elevated HIF-1alpha induces expression of
      multiple angiogenic factors, leading to vascular abnormality and tumour
      progression. In a genetic model of GBM, mice with an EC-specific defect in Pfn-1
      phosphorylation exhibit reduced tumour angiogenesis, normalized vasculature and
      improved survival. Moreover, EC-specific Pfn-1 phosphorylation is associated with
      tumour aggressiveness in human glioma. These findings suggest that targeting Pfn
      1 phosphorylation may offer a selective strategy for therapeutic intervention of
      malignant solid tumours. 

PMID- 24747442
TI  - Immobilised histidine tagged beta2-adrenoceptor oriented by a diazonium salt
      reaction and its application in exploring drug-protein interaction using
      ephedrine and pseudoephedrine as probes.
AB  - A new oriented method using a diazonium salt reaction was developed for linking
      beta2-adrenoceptor (beta2-AR) on the surface of macroporous silica gel.
      Stationary phase containing the immobilised receptor was used to investigate the
      interaction between beta2-AR and ephedrine plus pseudoephedrine by zonal elution.
      The isotherms of the two drugs best fit the Langmuir model. Only one type of
      binding site was found for ephedrine and pseudoephedrine targeting beta2-AR. At
      37  degrees C, the association constants during the binding were (5.94+/
      0.05)*103/M for ephedrine and (3.80+/-0.02) *103/M for pseudoephedrine, with the
      binding sites of (8.92+/-0.06) *10-4 M. Thermodynamic studies showed that the
      binding of the two compounds to beta2-AR was a spontaneous reaction with
      exothermal processes. The DeltaGtheta, DeltaHtheta and DeltaStheta for the
      interaction between ephedrine and beta2-AR were -(22.33+/-0.04) kJ/mol, -(6.51+/
      0.69) kJ/mol and 50.94+/-0.31 J/mol.K, respectively. For the binding of
      pseudoephedrine to the receptor, these values were -(21.17+/-0.02) kJ/mol, 
      (7.48+/-0.56) kJ/mol and 44.13+/-0.01 J/mol.K. Electrostatic interaction proved
      to be the driving force during the binding of the two drugs to beta2-AR. The
      proposed immobilised method will have great potential for attaching protein to
      solid substrates and realizing the interactions between proteins and drugs. 

PMID- 24747443
TI  - Capreomycin inhalable powders prepared with an innovative spray-drying technique.
AB  - The aim of the work was to produce inhalable capreomycin powders using a novel
      spray-drying technology. A 2(3) factorial design was used to individuate the best
      working conditions. The maximum desirability was identified at the smallest mean
      volume diameter (dv) and span, and the highest yield. Powders were characterized
      for size, morphology, flowability and aerodynamic properties. Mathematical models
      showed a good predictivity with biases lower than 20%. The maximum conformity
      with desirability criteria was obtained spraying a 10mg/mL bacitracin solution at
      111  degrees C with the 4 MUm pore size membrane. By processing capreomycin
      sulfate with the parameters optimized for bacitracin, an inhalable powder was
      obtained (i.e., yield of 82%, dv of 3.83 MUm, and span of 1.04). By further
      optimization, capreomycin sulfate powder characteristics were improved (i.e.,
      yield, ~71%; dv, 3.25 MUm; span, 0.95). After formulation with lactose, emitted
      dose and respirable fraction of 87% and ~27% were obtained, respectively. Two
      capreomycin sulfate powders with suitable properties for inhalation were produced
      using the nano spray-dryer B-90.

PMID- 24747441
TI  - An integrin beta3-KRAS-RalB complex drives tumour stemness and resistance to EGFR
      inhibition.
AB  - Tumour cells, with stem-like properties, are highly aggressive and often show
      drug resistance. Here, we reveal that integrin alpha(v)beta3 serves as a marker
      of breast, lung and pancreatic carcinomas with stem-like properties that are
      highly resistant to receptor tyrosine kinase inhibitors such as erlotinib. This
      was observed in vitro and in mice bearing patient-derived tumour xenografts or in
      clinical specimens from lung cancer patients who had progressed on erlotinib.
      Mechanistically, alpha(v)beta3, in the unliganded state, recruits KRAS and RalB
      to the tumour cell plasma membrane, leading to the activation of TBK1 and NF
      kappaB. In fact, alpha(v)beta3 expression and the resulting KRAS-RalB-NF-kappaB
      pathway were both necessary and sufficient for tumour initiation, anchorage
      independence, self-renewal and erlotinib resistance. Pharmacological targeting of
      this pathway with bortezomib reversed both tumour stemness and erlotinib
      resistance. These findings not only identify alpha(v)beta3 as a marker/driver of
      carcinoma stemness but also reveal a therapeutic strategy to sensitize such
      tumours to RTK inhibition.

PMID- 24747444
TI  - The moral pop-out effect: enhanced perceptual awareness of morally relevant
      stimuli.
AB  - People perceive religious and moral iconography in ambiguous objects, ranging
      from grilled cheese to bird feces. In the current research, we examined whether
      moral concerns can shape awareness of perceptually ambiguous stimuli. In three
      experiments, we presented masked moral and non-moral words around the threshold
      for conscious awareness as part of a lexical decision task. Participants
      correctly identified moral words more frequently than non-moral words-a
      phenomenon we term the moral pop-out effect. The moral pop-out effect was only
      evident when stimuli were presented at durations that made them perceptually
      ambiguous, but not when the stimuli were presented too quickly to perceive or
      slowly enough to easily perceive. The moral pop-out effect was not moderated by
      exposure to harm and cannot be explained by differences in arousal, valence, or
      extremity. Although most models of moral psychology assume the initial perception
      of moral stimuli, our research suggests that moral beliefs and values may shape
      perceptual awareness. 

PMID- 24747445
TI  - Traumatic brain injury causes platelet adenosine diphosphate and arachidonic acid
      receptor inhibition independent of hemorrhagic shock in humans and rats.
AB  - BACKGROUND: Coagulopathy in traumatic brain injury (CTBI) is a well-established
      phenomenon, but its mechanism is poorly understood. Various studies implicate
      protein C activation related to the global insult of hemorrhagic shock or brain
      tissue factor release with resultant platelet dysfunction and depletion of
      coagulation factors. We hypothesized that the platelet dysfunction of CTBI is a
      distinct phenomenon from the coagulopathy following hemorrhagic shock. METHODS:
      We used thrombelastography with platelet mapping as a measure of platelet
      function, assessing the degree of inhibition of the adenosine diphosphate (ADP)
      and arachidonic acid (AA) receptor pathways. First, we studied the early effect
      of TBI on platelet inhibition by performing thrombelastography with platelet
      mapping on rats. We then conducted an analysis of admission blood samples from
      trauma patients with isolated head injury (n = 70). Patients in shock or on
      clopidogrel or aspirin were excluded. RESULTS: In rats, ADP receptor inhibition
      at 15 minutes after injury was 77.6% +/- 6.7% versus 39.0% +/- 5.3% for controls
      (p < 0.0001). Humans with severe TBI (Glasgow Coma Scale [GCS] score <= 8) showed
      an increase in ADP receptor inhibition at 93.1% (interquartile range [IQR], 44.8
      98.3%; n = 29) compared with 56.5% (IQR, 35-79.1%; n = 41) in milder TBI and
      15.5% (IQR, 13.2-29.1%) in controls (p = 0.0014 and p < 0.0001, respectively). No
      patient had significant hypotension or acidosis. Parallel trends were noted in AA
      receptor inhibition. CONCLUSION: Platelet ADP and AA receptor inhibition is a
      prominent early feature of CTBI in humans and rats and is linked to the severity
      of brain injury in patients with isolated head trauma. This phenomenon is
      observed in the absence of hemorrhagic shock or multisystem injury. Thus, TBI
      alone is shown to be sufficient to induce a profound platelet dysfunction.

PMID- 24747446
TI  - Complex penetrating duodenal injuries: less is better.
AB  - BACKGROUND: The traditional management of complex penetrating duodenal trauma
      (PDT) has been the use of elaborate temporizing and complex procedures such as
      the pyloric exclusion and duodenal diverticulization. We sought to determine
      whether a simplified surgical approach to the management of complex PDT injuries
      improves clinical outcome. METHODS: A retrospective review of all consecutive PDT
      from 2003 to 2012 was conducted. Patients were divided into three groups
      according to a simplified surgical algorithm devised following the local
      experience at a regional Level I trauma center. Postoperative duodenal leaks were
      drained externally either via traditional anterior drainage or via posterior
      "retroperitoneal laparostomy" as an alternate option. RESULTS: There were 44
      consecutive patients with PDT, and 41 of them (93.2%) were from gunshot wounds.
      Seven patients were excluded owing to early intraoperative death secondary to
      associated devastating traumatic injuries. Of the remaining 36 patients, 7
      (19.4%) were managed with single-stage primary duodenal repair with definitive
      abdominal wall fascial closure (PDR + NoDC group). Damage-control laparotomy was
      performed in 29 patients, (80.5%) in which primary repair was performed in 15
      (51.7%) (PDR + DC group), and the duodenum was over sewn and left in
      discontinuity in 14 (48.3%). Duodenal reconstruction was performed after primary
      repair in 2 of 15 cases and after left in discontinuity in 13 of 14 cases (DR +
      DC group). The most common complication was the development of a duodenal fistula
      in 12 (33%) of 36 cases. These leaks were managed by traditional anterior
      drainage in 9 (75%) of 12 cases and posterior drainage by retroperitoneal
      laparostomy in 3 (25%) of 12 cases. The duodenal fistula closed spontaneously in
      7 (58.3%) of 12 cases. The duodenum-related mortality rate was 2.8%, and the
      overall mortality rate was 11.1%. CONCLUSION: An application of basic damage
      control techniques for PDT leads to improved survival and an acceptable incidence
      of complications. LEVEL OF EVIDENCE: Therapeutic study, level IV.

PMID- 24747447
TI  - Benchmarking trauma centers on mortality alone does not reflect quality of care:
      implications for pay-for-performance.
AB  - BACKGROUND: Trauma centers are currently benchmarked on mortality outcomes alone.
      However, pay-for-performance measures may financially penalize centers based on
      complications. Our objective was to determine whether the results would be
      similar to the current standard method of mortality-based benchmarking if trauma
      centers were profiled on complications. METHODS: We analyzed data from the
      National Trauma Data Bank from 2007 to 2010. Patients 16 years or older with
      blunt or penetrating injuries and an Injury Severity Score (ISS) of 9 or higher
      were included. Risk-adjusted observed-to-expected (O/E) mortality ratios for each
      center were generated and used to rank each facility as high, average, or low
      performing. We similarly ranked facilities on O/E morbidity ratios defined as
      occurrence of any major complication. Concordance between hospital performance
      rankings was evaluated using a weighted kappa statistic. Correlation between
      morbidity- and mortality-based O/E ratios was assessed using Pearson
      coefficients. Sensitivity analyses were performed to mitigate the competing risk
      of death for the morbidity analyses. RESULTS: A total of 449,743 patients from
      248 facilities were analyzed. The unadjusted morbidity and mortality rates were
      10.0% and 6.9%, respectively. No correlation was found between morbidity- and
      mortality-based O/E ratios (r = -0.01). Only 40% of the centers had similar
      performance rankings for both mortality and morbidity. Of the 31 high performers
      for mortality, only 11 centers were also high performers for morbidity. A total
      of 78 centers were ranked as average, and 11 ranked as low performers on both
      outcomes. Comparison of hospital performance status using mortality and morbidity
      outcomes demonstrated poor concordance (weighted kappa = 0.03, p = 0.22).
      CONCLUSION: Mortality-based external benchmarking does not identify centers with
      high complication rates. This creates a dichotomy between current trauma center
      profiling standards and measures used for pay-for-performance. A benchmarking
      mechanism that reflects all measures of quality is needed. LEVEL OF EVIDENCE:
      Prognostic/epidemiologic study, level III.

PMID- 24747448
TI  - To swab or not to swab? A prospective analysis of 341 SICU VRE screens.
AB  - BACKGROUND: Vancomycin-resistant Enterococcus (VRE) screening is routine practice
      in many intensive care units despite the question of its clinical significance.
      The value of VRE screening at predicting subsequent VRE or other hospital
      acquired infection (HAI) is unknown. The purpose of this investigation was to
      examine the rate of subsequent VRE HAI in patients undergoing VRE screening.
      METHODS: This study was conducted in a 24-bed surgical intensive care unit (SICU)
      at a Level I trauma center. Patients admitted to the SICU between February and
      August 2011 who had rectal swab for VRE screening within 72 hours were followed
      prospectively for the development of VRE and other HAIs. Demographics, clinical
      characteristics, and infection rates were compared between VRE-positive and VRE
      negative patients. Sensitivity, specificity, positive predictive value (PPV), and
      negative predictive value (NPV) of VRE screening for predicting subsequent VRE
      HAI were calculated. RESULTS: A total of 341 patients had VRE screening within 72
      hours of SICU admission, with 32 VRE-positive (9%) and 309 VRE-negative (91%)
      patients. VRE-positive patients had a higher incidence of any HAI (78% vs. 35%, p
      < 0.001). Eight VRE-positive patients (25%) developed VRE HAI compared with only
      3 VRE-negative patients (1%) (p < 0.001). VRE screening had a 73% sensitivity,
      93% specificity, 25% PPV, and 99% NPV for determining subsequent VRE HAI.
      CONCLUSION: VRE colonization was present in 9% of SICU patients at admission.
      Negative VRE screen result had a high specificity and NPV for the development of
      subsequent VRE HAI. Empiric treatment of VRE infection may be unnecessary in VRE
      negative patients. LEVEL OF EVIDENCE: Prognostic/epidemiologic study, level III.
      Therapeutic study, level IV.

PMID- 24747449
TI  - Open extremity fractures: impact of delay in operative debridement and
      irrigation.
AB  - BACKGROUND: Early (<8 hours) operative debridement and irrigation (D&I) of open
      fractures are considered essential to reduce the risk of deep infection. With the
      advent of powerful antimicrobials, this axiom has been challenged. The current
      study evaluates the rates of deep infections of open fractures in relation to the
      time to the first D&I. METHODS: A list of all blunt open fractures during a 6
      year period was obtained from the trauma registry. Patients were evaluated for
      age, Injury Severity Score (ISS), physiologic derangement (systolic blood
      pressure, lactate, Revised Trauma Score [RTS]), and fracture type (Gustilo). Time
      to the first D&I was calculated. All patients received appropriate prophylactic
      antimicrobials. Infection rates were calculated and correlated to the time to the
      first D&I (<8 hours vs. >8 hours). Regression analysis was performed to identify
      independent predictors of infection. RESULTS: During the 72-month study period,
      404 patients met entry criteria, with 415 open extremity fractures (upper, 129;
      lower, 287). Early (<8 hours) and delayed (>8 hours) groups were well matched,
      although the age was lower and ISS was higher in the group with greater than 8
      hours. The rates of infection were 35 (11%) of 328 (<8 hour) and 17 (19%) of 87
      (>8 hours) (p < 0.05). When fractures were subgrouped by extremity, for the lower
      extremity, both a delay of greater than 8 hours and higher Gustilo type
      correlated with the development of infection. In the upper extremity, only higher
      Gustilo type correlated, and a delay to the first D&I did not increase the
      incidence of infection. Regression analysis revealed that higher ISS (odd ratio
      [OR], 1.052; 95% confidence interval [CI], 1.019-1.086), Gustilo grade, and a
      delay of greater than 8 hours (OR, 2.035; 95% CI, 1.022-4.054) were independent
      predictors of infection for the all-extremity model. Separate models for upper
      and lower extremities showed that the same three parameters were independent
      predictors for the lower extremity (ISS: OR, 1.045; 95% CI, 1.004-1.087; Gustilo
      type and >8-hour delay: OR, 3.006; 95% CI, 1.280-7.059), but none for the upper
      extremity. CONCLUSION: Delay of greater than 8 hours to the first D&I for open
      fractures of the lower extremity increases the likelihood of infection but not
      for the upper extremity. Higher Gustilo type open fractures have a higher
      incidence of infection for both upper and lower extremities. The results have
      important implications in an era of decreasing surgeon availability, especially
      in off hours. LEVEL OF EVIDENCE: Therapeutic study, level IV.

PMID- 24747450
TI  - Operation PeaceWorks: a community program with the participation of a Level II
      trauma center to decrease gang-related violence.
AB  - BACKGROUND: Gang-related violence is a major public health problem. A gang
      prevention program (Operation PeaceWorks) was developed in Ventura County,
      California, to help trauma patients who were gang members quit gang lifestyles.
      The purpose of this study was to determine the incidence of gang-related violence
      in the community before and after establishing Operation PeaceWorks. METHODS: In
      Operation PeaceWorks, participating gang members were mentored, counseled,
      offered job training, and provided with opportunities to further their education
      or secure employment. Data about gang-related activity in the community were
      identified and recorded. The number of gang-related assaults (total), assaults
      involving firearms, and homicides were determined and compared before and after
      the start of the program. RESULTS: During the 3 years after starting Operation
      PeaceWorks (2010-2012), the program had 3,430 interventions with 1,464 gang
      members (2.3 interventions per gang member). Three years after starting Operation
      PeaceWorks, there was a significant decrease in mean annual total gang assaults (
      16%, p < 0.001), assaults with firearms (-32%, p < 0.001), and homicides (-47%, p
      = 0.05) compared with the 7 years before Operation PeaceWorks. CONCLUSION: A
      multidisciplinary community gang prevention program, with the participation of
      the trauma center, may be effective in decreasing gang-related trauma. The
      experience with this program may contribute to the development of further
      evidence-based programs to decrease gang-related trauma. LEVEL OF EVIDENCE:
      Epidemiologic study, level III. Therapeutic study, level IV.

PMID- 24747451
TI  - Mesenteric lymph diversion abrogates 5-lipoxygenase activation in the kidney
      following trauma and hemorrhagic shock.
AB  - BACKGROUND: Early acute kidney injury (AKI) following trauma is associated with
      multiorgan failure and mortality. Leukotrienes have been implicated both in AKI
      and in acute lung injury. Activated 5-lipoxygenase (5-LO) colocalizes with 5-LO
      activating protein (FLAP) in the first step of leukotriene production following
      trauma and hemorrhagic shock (T/HS). Diversion of postshock mesenteric lymph,
      which is rich in the 5-LO substrate of arachidonate, attenuates lung injury and
      decreases 5-LO/FLAP associations in the lung after T/HS. We hypothesized that
      mesenteric lymph diversion (MLD) will also attenuate postshock 5-LO-mediated AKI.
      METHODS: Rats underwent T/HS (laparotomy, hemorrhagic shock to a mean arterial
      pressure of 30 mm Hg for 45 minutes, and resuscitation), and MLD was accomplished
      via cannulation of the mesenteric duct. Extent of kidney injury was determined
      via histology score and verified by urinary neutrophil gelatinase-associated
      lipocalin assay. Kidney sections were immunostained for 5-LO and FLAP, and
      colocalization was determined by fluorescence resonance energy transfer signal
      intensity. The end leukotriene products of 5-LO were determined in urine.
      RESULTS: AKI was evident in the T/HS group by derangement in kidney tubule
      architecture and confirmed by neutrophil gelatinase-associated lipocalin assay,
      whereas MLD during T/HS preserved renal tubule morphology at a sham level. MLD
      during T/HS decreased the associations between 5-LO and FLAP demonstrated by
      fluorescence resonance energy transfer microscopy and decreased leukotriene
      production in urine. CONCLUSION: 5-LO and FLAP colocalize in the interstitium of
      the renal medulla following T/HS. MLD attenuates this phenomenon, which coincides
      with pathologic changes seen in tubules during kidney injury and biochemical
      evidence of AKI. These data suggest that gut-derived leukotriene substrate
      predisposes the kidney and the lung to subsequent injury.

PMID- 24747452
TI  - Mitochondrial damage-associated molecular patterns released by abdominal trauma
      suppress pulmonary immune responses.
AB  - BACKGROUND: Historically, fever, pneumonia, and sepsis after trauma are ascribed
      to pain and poor pulmonary toilet. No evidence supports that assertion however,
      and no known biologic mechanisms link injury to infection. Our studies show that
      injured tissues release mitochondria (MT). Mitochondrial damage-associated
      molecular patterns (mtDAMPs) however can mimic bacterial pathogen-associated
      danger molecules and attract neutrophils (PMN). We hypothesized that mtDAMPs from
      traumatized tissue divert neutrophils from the lung, causing susceptibility to
      infection. METHODS: Anesthetized rats (6-10 per group) underwent pulmonary
      contusion (PC) by chest percussion. When modeling traumatic MT release, some rats
      had MT isolated from the liver (equal to 5% liver necrosis) injected
      intraperitoneally (IPMT). Negative controls had PC plus buffer intraperitoneally.
      Positive controls underwent PC plus cecal ligation and puncture. At 16 hours,
      bronchoalveolar and peritoneal lavages were performed. Bronchoalveolar lavage
      fluid (BALF) and peritoneal lavage fluid were assayed for PMN count, albumin,
      interleukin beta, (IL-beta), and CINC-1. Assays were normalized to blood urea
      nitrogen to calculate absolute concentrations. RESULTS: PC caused alveolar IL
      1beta and CINC production and a 34-fold increase in BALF neutrophils. As
      expected, IPMT increased peritoneal IL-1beta and CINC and attracted PMN to the
      abdomen. However, remarkably, IPMT after PC attenuated BALF cytokine accumulation
      and decreased BALF PMN. Cecal ligation and puncture had no direct effect on BALF
      PMNs but, like IPMT, blunted BALF leukocytosis after PC. CONCLUSION: Rather than
      acting as a "second hit" to enhance PMN-mediated lung injury, mtDAMPs from trauma
      and pathogen-associated danger molecules from peritoneal infection diminish PMN
      accumulation in a contused lung. This may make the lung susceptible to pneumonia.
      This paradigm provides a novel mechanistic model of the relationship among blunt
      tissue trauma, systemic inflammation, and pneumonia that can be studied to
      improve trauma outcomes.

PMID- 24747453
TI  - Protective effects of erythropoietin in traumatic spinal cord injury by inducing
      the Nrf2 signaling pathway activation.
AB  - BACKGROUND: Erythropoietin has demonstrated neuroprotective effects against
      traumatic spinal cord injury (SCI), but the underlying mechanisms remain unclear.
      The signaling pathway of an antioxidant transcription factor, nuclear factor
      erythroid 2-related factor 2 (Nrf2), has been shown to play an important role in
      protecting SCI-induced secondary spinal cord damage. This study was undertaken to
      explore the effect of recombinant human erythropoietin (rhEPO) on the activation
      of Nrf2 signaling pathway and secondary spinal cord damage in rats after SCI.
      METHODS: Adult male Sprague-Dawley rats were subjected to laminectomy at T8-T9
      and compression with a vascular clip. Three groups were analyzed: (1) sham group,
      (2) SCI group, and (3) SCI + rhEPO group (n = 16 per group). In the SCI + rhEPO
      group, rhEPO was administered at a dose of 5,000 IU/kg at 30 minutes after SCI.
      Spinal cord samples were extracted at 72 hours after the trauma. RESULTS: As a
      result, we found that the treatment with rhEPO markedly up-regulated the
      messenger RNA expressions and activities of Nrf2 signaling pathway-related
      agents, including Nrf2, NAD(P)H:quinone oxidoreductase 1(NQO1), and glutathione S
      transferase. The administration of rhEPO also significantly ameliorated the
      secondary spinal cord damage, as shown by a decreased severity of locomotion
      deficit, spinal cord edema, and apoptosis. CONCLUSION: Post-SCI rhEPO
      administration induces Nrf2-mediated cytoprotective response in the injured
      spinal cord, and this may be a mechanism whereby rhEPO improves the outcome
      following SCI.

PMID- 24747454
TI  - Recovery of fibrinogen concentrate after intraosseous application is equivalent
      to the intravenous route in a porcine model of hemodilution.
AB  - BACKGROUND: Fibrinogen concentrate is increasingly considered as a hemostatic
      agent for trauma patients experiencing bleeding. Placing a venous access is
      sometimes challenging during severe hemorrhage. Intraosseous access may be
      considered instead. Studies of intraosseous infusion of coagulation factor
      concentrates are limited. We investigated in vivo recovery following intraosseous
      administration of fibrinogen concentrate and compared the results with
      intravenous administration. METHODS: This study was performed on 12 pigs (mean
      [SD] body weight, 34.1 [2.8] kg). Following controlled blood loss (35 mL/kg) and
      fluid replacement with balanced crystalloid solution, intraosseous (n = 6)
      administration of fibrinogen concentrate (80 mg per kilogram of bodyweight) in
      the proximal tibia was compared with intravenous (n = 6) administration of the
      same dose (fibrinogen infusion time approximately 5 minutes in both groups). The
      following laboratory parameters were assessed: blood cell count, prothrombin time
      index, activated partial thromboplastin time, and plasma fibrinogen concentration
      (Clauss assay). Coagulation status was also assessed by thromboelastometry.
      RESULTS: All tested laboratory parameters were comparable between the
      intraosseous and intravenous groups at baseline, hemodilution, and 30 minutes
      after fibrinogen concentrate administration. In vivo recovery of fibrinogen was
      also similar in the two groups (89% [23%] and 91% [22%], respectively). There
      were no significant between-group differences in any of the thromboelastometric
      parameters. Histologic examination indicated no adverse effects on the tissue
      surrounding the intraosseous administration site. CONCLUSION: This study suggests
      that intraosseous administration of fibrinogen concentrate results in a recovery
      of fibrinogen similar to that of intravenous administration. The intraosseous
      route of fibrinogen concentrate could be a valuable alternative in situations
      where intravenous access is not feasible or would be time consuming. LEVEL OF
      EVIDENCE: Prospective, randomized, therapeutic feasibility study in an animal
      model, level V.

PMID- 24747455
TI  - Predicting the need for massive transfusion in trauma patients: the Traumatic
      Bleeding Severity Score.
AB  - BACKGROUND: The ability to easily predict the need for massive transfusion may
      improve the process of care, allowing early mobilization of resources. There are
      currently no clear criteria to activate massive transfusion in severely injured
      trauma patients. The aims of this study were to create a scoring system to
      predict the need for massive transfusion and then to validate this scoring
      system. METHODS: We reviewed the records of 119 severely injured trauma patients
      and identified massive transfusion predictors using statistical methods. Each
      predictor was converted into a simple score based on the odds ratio in a
      multivariate logistic regression analysis. The Traumatic Bleeding Severity Score
      (TBSS) was defined as the sum of the component scores. The predictive value of
      the TBSS for massive transfusion was then validated, using data from 113 severely
      injured trauma patients. Receiver operating characteristic curve analysis was
      performed to compare the results of TBSS with the Trauma-Associated Severe
      Hemorrhage score and the Assessment of Blood Consumption score. RESULTS: In the
      development phase, five predictors of massive transfusion were identified,
      including age, systolic blood pressure, the Focused Assessment with Sonography
      for Trauma scan, severity of pelvic fracture, and lactate level. The maximum TBSS
      is 57 points. In the validation study, the average TBSS in patients who received
      massive transfusion was significantly greater (24.2 [6.7]) than the score of
      patients who did not (6.2 [4.7]) (p < 0.01). The area under the receiver
      operating characteristic curve, sensitivity, and specificity for a TBSS greater
      than 15 points was 0.985 (significantly higher than the other scoring systems
      evaluated at 0.892 and 0.813, respectively), 97.4%, and 96.2%, respectively.
      CONCLUSION: The TBSS is simple to calculate using an available iOS application
      and is accurate in predicting the need for massive transfusion. Additional
      multicenter studies are needed to further validate this scoring system and
      further assess its utility. LEVEL OF EVIDENCE: Prognostic study, level III.

PMID- 24747456
TI  - Defining the optimal time to the operating room may salvage early trauma deaths.
AB  - BACKGROUND: Early trauma deaths have the potential for salvage with immediate
      surgery. We studied time from injury to death in this group to qualify
      characteristics and quantify time to the operating room, yielding the greatest
      opportunity for salvage. METHODS: The Pennsylvania Trauma Outcomes Study (PTOS)
      is a comprehensive registry including all Pennsylvania trauma centers. PTOS was
      queried for adult trauma patients from 1999 to 2010 dying within 4 hours of
      injury. The distribution of time to death (TD) was examined for subgroups
      according to mechanism of injury, hypotension (defined as systolic blood pressure
      <= 90 mm Hg), and operation required. The 5th percentile (TD5) and the 50th
      percentile (TD50) were calculated from the distributions and compared using the
      Mann-Whitney U-test. RESULTS: The PTOS yielded 6,547 deaths within 4 hours of
      injury. The overall TD5 and TD50 were 0:23 (hour:minute) and 0:59, respectively.
      Median penetrating injury times were significantly shorter than blunt injury
      times (TD5/TD50, 0:19/0:43 vs. 0:29/1:10). Median time was significantly shorter
      for hypotensive versus normotensive patients (TD5/TD50, 0:22/0:52 vs. 0:43/2:18).
      Operative subgroups had different TD5/TD50 (abdominal surgery [n = 607],
      1:07/2:26; thoracic surgery [n = 756] 0:25/1:25; vascular surgery [n = 156],
      0:35/2:15; and cranial surgery [n = 18], 1:20/2:42). CONCLUSION: Early trauma
      deaths have the potential for salvage with immediate surgery. We found TD to vary
      based on mechanism of injury, presence of hypotension, and type of surgery
      needed. With the use of TD5 and TD50 benchmarks in these subgroups, a trauma
      system may determine if decreased time to the operating room decreases mortality.
      Trauma systems can use these data to further improve prehospital and initial
      hospital phases of care for this subset of early death trauma patients. LEVEL OF
      EVIDENCE: Epidemiologic study, level III.

PMID- 24747457
TI  - Predicting the need for abdominal hemorrhage control in major pelvic fracture
      patients: the importance of quantifying the amount of free fluid.
AB  - BACKGROUND: In our institution, the computed tomographic (CT) scan has largely
      replaced the ultrasound for the rapid detection of intraperitoneal free fluid
      (FF) and abdominal injuries in severely injured patients.We hypothesized that in
      major pelvic fracture patients, quantifying the size of FF on CT improves the
      predictive value for the need for abdominal hemorrhage control (AHC). METHODS:
      The CT scans of major pelvic fracture (pelvic ring disruption) patients (January
      1, 2004, to June 31, 2012) were reviewed for the presence of FF (small, moderate,
      or large amount) and abdominal injuries. AHC was defined as requiring a surgical
      intervention for active abdominal bleeding or angiographic embolization for an
      abdominal arterial injury.Positive predictive value (PPV) and negative predictive
      value (NPV) (95% confidence interval [CI]) were calculated for all patients and
      in a subgroup of patients with a high risk for significant hemorrhage (base
      deficit >= 6 mEq/L). RESULTS: Overall, 160 patients were included in the study.
      Of the 62 FF patients, 26 required AHC (PPV, 42%, 95% CI, 30-55%). Of the 98
      patients without FF, none required AHC (NPV, 100%; 95% CI, 95-100%). For a
      moderate-to-large amount of FF, the PPV and NPV in all patients were 81% (95% CI,
      60-93%) and 96% (95% CI, 91-99%), respectively.In the subgroup of 49 high-risk
      patients (31%), 17 of 26 FF patients required AHC (PPV, 65%; 95% CI, 44-82%), and
      none of the 23 patients without FF required AHC (NPV, 100%; 95% CI, 82-100%). For
      a moderate-to-large amount, the PPV and NPV in high-risk patients were 93% (95%
      CI, 64-100%) and 89% (95% CI, 72-96%), respectively. CONCLUSION: In major pelvic
      fracture patients, the predictive value of FF on CT for the need for AHC is
      closely related to the amount present. A moderate-to-large amount of FF is highly
      predictive for the presence of abdominal bleeding that requires hemorrhage
      control. LEVEL OF EVIDENCE: Therapeutic study, level IV; prognostic study, level
      III.

PMID- 24747458
TI  - Guiding the management of intubated patients with pneumonia and ventilator
      associated events using serial catheter-directed bronchoalveolar lavage.
AB  - BACKGROUND: We evaluated the role of serial catheter-directed bronchoalveolar
      lavage (CDBAL) in the diagnosis and management of pneumonia in ventilated
      surgical intensive care unit patients. METHODS: Intubated surgical intensive care
      unit patients were prospectively evaluated with serial CDBALs from September 1,
      2012, to May 31, 2013. Initial CDBALs were performed if patients developed the
      following signs of pneumonia: white blood cell count greater than 11 or less than
      4, temperature greater than 38.5 degrees C or less than 36 degrees C, qualitative
      purulent sputum, worsening oxygenation, or new infiltrate on plain chest x-ray.
      Subsequent CDBALs were performed every 4 days. Pneumonia was diagnosed using a
      Clinical Pulmonary Infection Score of greater than 6 and CDBAL cultures with
      greater than or equal to 10 colony-forming units of pathogenic organisms.
      Patients were also evaluated for sustained (>=48 hours) respiratory deterioration
      (increased FIO2 or positive end-expiratory pressure) corresponding to the
      National Healthcare Safety Network definition of ventilator-associated event
      (VAE). RESULTS: A total of 159 patients were intubated for 5 days or longer, of
      whom 80 patients were diagnosed with clinical pneumonia. Of these patients, 67
      had serial CDBALs performed, and 81 ventilator-associated pneumonias (VAPs) were
      diagnosed in these patients. Of the patients with VAP, 16 also met the National
      Healthcare Safety Network criteria for VAE. Patients with VAP that had sustained
      respiratory deterioration demonstrated resolution of their compromise 60 hours
      (interquartile range [IQR], 41-107 hours) after starting antibiotics. Of the
      patients with pneumonia, 66 (81%) had resolution of the pathogenic bacteria in
      subsequent CDBAL cultures or were extubated within 4 days (IQR, 4-5 days) after
      starting antibiotics. The duration of antibiotic therapy in this group was 8 days
      (IQR, 7-9 days). The remaining 15 patients had multiple positive serial CDBAL
      cultures that isolated the same organism despite antibiotic treatment. The
      duration of antibiotic therapy was 14 days (IQR, 10-19 days) in these patients.
      The culture results were used to adjust antibiotic regimens a median of one time
      (IQR, 1-2 times) in 13 (87%) and two or more times in 6 (40%) of these patients.
      CONCLUSION: Serial CDBALs help guide antibiotic treatment duration in patients
      with pneumonia and VAE. Patients with sustained hypoxia or persistent bacterial
      growth may require prolonged therapy. LEVEL OF EVIDENCE: Diagnostic test, level
      III. Therapeutic study, level IV.

PMID- 24747459
TI  - Pulmonary embolism without deep venous thrombosis: De novo or missed deep venous
      thrombosis?
AB  - BACKGROUND: Pulmonary embolus (PE) is thought to arise from a deep venous
      thrombosis (DVT). Recent data suggest that PE can present without DVT, inferring
      that PE can originate de novo (DNPE). We examined the relationship between DVT
      and PE in trauma patients screened for DVT with duplex sonography (DS). We sought
      to validate the incidence of PE without evidence of DVT and to examine the
      clinical significance of this entity. METHODS: We reviewed the medical records of
      all trauma patients from July 2006 to December 2011 with PE who also had serial
      surveillance DS (groin to ankle). Demographics, severity of injury,
      interventions, signs and symptoms of PE, as well as chest computerized tomography
      findings were collected. Patients with no DS evidence of DVT either before or
      within 48 hours of PE diagnosis (DNPE) were compared with those with DVT (PE +
      DVT). RESULTS: Of 11,330 patients evaluated by the trauma service, 2,881 patients
      received at least one DS. PE occurred in 31 of these patients (1.08%): 19 (61%)
      were DNPE, and 12 (39%) were PE + DVT. Compared with patients with PE + DVT,
      patients with DNPE were significantly younger and had more rib fractures,
      pulmonary contusions, infections, pulmonary symptoms, and peripherally located
      PEs on computerized tomography. CONCLUSION: This is the first report of the
      clinical course of DNPE without embolic origin in a population with comprehensive
      duplex surveillance. In our series, DNPE seems to be more prevalent after trauma,
      to be clinically distinct from PE following DVT, and to likely represent a local
      response to injury or inflammation; however, further research is warranted to
      fully understand the pathophysiology of DNPE. LEVEL OF EVIDENCE: Care management
      study, level III.

PMID- 24747460
TI  - Venovenous extracorporeal life support improves survival in adult trauma patients
      with acute hypoxemic respiratory failure: a multicenter retrospective cohort
      study.
AB  - BACKGROUND: Venovenous extracorporeal life support (VV ECLS) has been reported in
      adult trauma patients with severe respiratory failure; however, ECLS is not
      available in many trauma centers, few trauma surgeons have experience initiating
      ECLS and managing ECLS patients, and there is currently little evidence
      supporting its use in severely injured patients. This study seeks to determine if
      VV ECLS improves survival in such patients. METHODS: Data from two American
      College of Surgeons-verified Level 1 trauma centers, which maintain detailed
      records of patients with acute hypoxemic respiratory failure (AHRF), were
      evaluated retrospectively. The study population included trauma patients between
      16 years and 55 years of age treated for AHRF between January 2001 and December
      2009. These patients were divided into two cohorts as follows: patients who
      received VV ECLS after an incomplete or no response to other rescue therapies
      (ECLS) versus patients who were managed with mechanical ventilation (CONV). The
      primary outcome was survival to discharge, and secondary outcomes were intensive
      care unit and hospital length of stay (LOS), total ventilator days, and rate of
      complications requiring intervention. RESULTS: Twenty-six ECLS patients and 76
      CONV patients were compared. Adjusted survival was greater in the ECLS group
      (adjusted odds ratio, 0.193; 95% confidence interval, 0.042-0.884; p = 0.034).
      Ventilator days, intensive care unit LOS, and hospital LOS did not differ between
      the groups. ECLS patients received more blood transfusions and had more bleeding
      complications, while the CONV patients had more pulmonary complications. A cohort
      of 17 ECLS and 17 CONV patients matched for age and lung injury severity also
      demonstrated a significantly greater survival in the ECLS group (adjusted odds
      ratio, 0.038; 95% confidence interval, 0.004-0.407; p = 0.007). CONCLUSION: VV
      ECLS is independently associated with survival in adult trauma patients with
      AHRF. ECLS should be considered in trauma patients with AHRF when conventional
      therapies prove ineffective; if ECLS is not readily available, transfer to an
      ECLS center should be pursued. LEVEL OF EVIDENCE: Therapeutic study, level III.

PMID- 24747461
TI  - External validation of the Blunt Abdominal Trauma in Children (BATiC) score:
      ruling out significant abdominal injury in children.
AB  - BACKGROUND: The aim of this study was to validate the use of the Blunt Abdominal
      Trauma in Children (BATiC) score. The BATiC score uses only readily available
      laboratory parameters, ultrasound results, and results from physical examination
      and does therefore not carry any risk of additional radiation exposure. METHODS:
      Data of pediatric trauma patients admitted to the shock room between 2006 and
      2010 were retrospectively analyzed. Blunt abdominal trauma was defined
      radiologically or surgically. The BATiC score was computed using 10 parameters as
      follows: abnormal abdominal ultrasound finding, abdominal pain, peritoneal
      irritation, hemodynamic instability, aspartate aminotransferase greater than 60
      U/L, alanine aminotransferase greater than 25 U/L, white blood cell count greater
      than 10 * 10/L, lactate dehydrogenase greater than 330 U/L, amylase greater than
      100 U/L, and creatinine greater than 110 MUmol/L. Sensitivity, specificity,
      negative predictive value, and positive predictive value were computed. Missing
      values were replaced using multiple imputation, and BATiC scores were calculated
      based on imputed values. RESULTS: Included were 216 patients, with 144 males, 72
      females, and a median age of 12 years. Eighteen patients (8%) sustained abdominal
      injury. Median BATiC scores of patients with and without intra-abdominal injury
      were 9.2 (range, 6.6-15.4) and 2.2 (range, 0.0-10.6) respectively (p < 0.001).
      When the BATiC score is used with a cutoff point of 6, the test showed a
      sensitivity of 100% and a specificity of 87%. Negative and positive predictive
      values were 100% and 41% respectively. The area under the curve was 0.98.
      CONCLUSION: The BATiC score can be a useful adjunct in the assessment of the
      presence of abdominal trauma in children and can help determine which patients
      might benefit from a computed tomographic scan and/or further treatment and which
      might not. LEVEL OF EVIDENCE: Prognostic study, level II.

PMID- 24747462
TI  - A risk-adapted approach is beneficial in the management of bilateral femoral
      shaft fractures in multiple trauma patients: an analysis based on the trauma
      registry of the German Trauma Society.
AB  - BACKGROUND: Today, there is a trend toward damage-control orthopedics (DCO) in
      the management of multiple trauma patients with long bone fractures. However,
      there is no widely accepted concept. A risk-adapted approach seems to result in
      low acute morbidity and mortality. Multiple trauma patients with bilateral
      femoral shaft fractures (FSFs) are considered to be more severely injured. The
      objective of this study was to validate the risk-adapted approach in the
      management of multiple trauma patients with bilateral FSF. METHODS: Data analysis
      is based on the trauma registry of the German Trauma Society (1993-2008, n =
      42,248). Multiple trauma patients with bilateral FSF were analyzed in subgroups
      according to the type of primary operative strategy. Outcome parameters were
      mortality and major complications as (multiple) organ failure and sepsis.
      RESULTS: A total of 379 patients with bilateral FSF were divided into four groups
      as follows: (1) no operation (8.4%), (2) bilateral temporary external fixation
      (DCO) (50.9%), bilateral primary definitive osteosynthesis (early total care
      [ETC]) (25.1%), and primary definitive osteosynthesis of one FSF and DCO
      contralaterally (mixed) (15.6%). Compared with the ETC group, the DCO group was
      more severely injured. The incidence of (multiple) organ failure and mortality
      rates were higher in the DCO group but without significance. Adjusted for injury
      severity, there was no significant difference of mortality rates between DCO and
      ETC. Injury severity and mortality rates were significantly increased in the no
      operation group. The mixed group was similar to the ETC group regarding injury
      severity and outcome. CONCLUSION: In Germany, both DCO and ETC are practiced in
      multiple trauma patients with bilateral FSF so far. The unstable or potentially
      unstable patient is reasonably treated with DCO. The clearly stable patient is
      reasonably treated with nailing. When in doubt, the patient is probably not
      totally stable, and the safest precaution may be to use DCO as a risk-adapted
      approach. LEVEL OF EVIDENCE: Therapeutic study, level IV. Epidemiologic study,
      level III.

PMID- 24747463
TI  - Retrospective analysis of facial dog bite injuries at a Level I trauma center in
      the Denver metro area.
AB  - BACKGROUND: Facial dog bite injuries pose a significant public health problem.
      METHODS: Seventy-five consecutive patients (45 males, 30 females) treated solely
      by plastic surgery service for facial dog bite injuries at a Level I trauma
      center in the Denver Metro area between 2006 and 2012 were retrospectively
      reviewed. The following information were recorded: breed, relationship of patient
      to dog, location and number of wounds, the duration between injury and surgical
      repair and dog bite incident, type of repair, and antibiotic prophylaxis. Primary
      end points measured were wound infection, the need for revision surgery, and
      patient satisfaction. RESULTS: Ninety-eight wounds in the head and neck region
      were repaired (46 children; mean age, 6.8 years) and (29 adults; mean age, 47.3
      years). Twelve different breeds were identified. There was no significant
      association between the type of dog breed and the number of bite injuries. The
      duration between injury and repair ranged from 4 hours to 72 hours (mean [SD],
      13.7 [10.9] hours). The majority of bite wounds (76 of 98) involved the cheek,
      lip, nose, and chin region. Direct repair was the most common surgical approach
      (60 of 98 wounds) (p < 0.05). There was no statistically significant association
      between wounds needing reconstruction versus direct repair according to dog breed
      (p = 0.25). Ten wounds required grafting. Twenty-five wounds were managed by one
      stage or two-stage flaps. Only three patients (3.06 %) underwent
      replantation/revascularization of amputated partial lip (n = 2) and of cheek (n =
      1). There was one postoperative infection. Data from five-point Likert scale were
      available for fifty-two patients. Forty patients were satisfied (5) with the
      outcome, while five patients were somewhat satisfied (4), and seven were neutral.
      CONCLUSION: Availability of the plastic surgery service at a Level I trauma
      center is vital for the optimal treatment of facial dog bite injuries. Direct
      repair and reconstruction of facial dog bite injuries at the earliest opportunity
      resulted in good outcomes as evidenced by the satisfaction survey data and low
      complication rate. LEVEL OF EVIDENCE: Therapeutic study, level V. Epidemiologic
      study, level III.

PMID- 24747464
TI  - Levothyroxine therapy before brain death declaration increases the number of
      solid organ donations.
AB  - BACKGROUND: Protocols call for the start of hormonal therapy with levothyroxine
      after the declaration of brain death. As the hormonal perturbations occur during
      the process of brain death, the role of the early initiation of levothyroxine
      therapy (LT) to salvage organs is not well defined. The aim of this study was to
      evaluate the impact of early LT (before the declaration of brain death) on the
      number of solid organs procured per donor. METHODS: We performed an 8-year
      retrospective analysis of all trauma patients who progressed to brain death.
      Patients who consented for organ donation, received LT, and donated solid organs
      were included. Patients were dichotomized into two groups: early LT group,
      patients who received LT before the declaration of brain death, and late LT
      group, those who received LT after brain death. The two groups were compared for
      differences in demographics, clinical characteristics, need for vasopressor, and
      number of solid organ donation. RESULTS: A total of 100 solid organ donors were
      identified of which, 41% (n=77) donors who received LT therapy were included. LT
      before the declaration of brain death was initiated in 37 patients compared with
      40 patients who had it started after the declaration of brain death. There was no
      difference in demographics between the two groups except that patients in the
      early LT group were more likely to be hypotensive on presentation (54% vs. 25%, p
      = 0.001). Early LT therapy was associated with an increase in solid organ
      procurement rate (odds ratio, 1.9; 95% confidence interval, 1.4-2.7; p = 0.01).
      Sixty-seven patients donated a total of 291 solid organs. CONCLUSION: The early
      use of LT and aggressive blood product resuscitation was associated with a
      significantly higher number of solid organs donated per donor. Earlier use of LT
      before the declaration of brain death may be considered in potential organ
      donors. LEVEL OF EVIDENCE: Therapeutic/care management study, level IV.

PMID- 24747465
TI  - Preinjury ambulatory status is associated with 1-year mortality following lateral
      compression Type I fractures in the geriatric population older than 80 years.
AB  - BACKGROUND: Lateral compression pelvic Type I fractures in the elderly population
      are most often low-energy osteoporosis related fractures. Previous literature
      comparing pelvic fractures in young versus elderly patients called into question
      the general consideration of these injuries as benign injuries with favorable
      prognoses; however, the geriatric population older than 80 years is often
      underrepresented. This article focuses on the mortality and functional outcomes
      after low-energy pelvic fractures in a population of patients older than 80
      years. METHODS: We prescreened potential subjects in a Level I trauma
      institution's electronic medical record database between January 1, 2002, and
      April 30, 2012, to identify isolated lateral compression Type 1 fractures treated
      nonoperatively in patients older than 80 years. This study was composed of a
      retrospective review of medical records followed by a prospective survey data
      collection to examine mechanisms of injury, length of hospital stay,
      complications, medical comorbidities, ambulatory function, living situation,
      pain, and 1 year mortality rates. RESULTS: We present a large case series of 85
      patients older than 80 years and report a 1-year mortality rate of 20%. We found
      that patients who were household ambulators or nonfunctional ambulators were five
      times more likely (24.4% vs. 6.1%) to die within 1 year after injury.
      Multivariate logistic regression confirmed that the risk of 1-year mortality was
      significantly higher for household-bound patients compared with community
      ambulators, independent of sex, smoking, Charlson comorbidity index, or length of
      hospital stay. CONCLUSION: This is the first study to demonstrate a difference in
      1-year mortality between patients who were community ambulators versus those who
      were household ambulators or nonfunctional ambulators before injury. With our
      aging population, these findings have important implications. Maintenance of
      general conditioning and early mobilization with physical therapy after injury is
      a key part of geriatric orthopedic rehabilitation. LEVEL OF EVIDENCE: Prognostic
      and epidemiologic, level IV.

PMID- 24747466
TI  - Derivation and validation of a quality indicator for 30-day unplanned hospital
      readmission to evaluate trauma care.
AB  - BACKGROUND: Unplanned readmissions represent 20% of all admissions and cost $12
      billion annually in the United States. Despite the burden of injuries for the
      health care system, no quality indicator (QI) based on readmissions is available
      to evaluate trauma care. The objective of this study was to derive and internally
      validate a QI for a 30-day unplanned hospital readmission to evaluate trauma
      care. METHODS: We performed a multicenter retrospective cohort study in a
      Canadian integrated provincial trauma system. We included adults admitted to any
      of the 57 provincial trauma centers between 2005 and 2010 (n = 57,524). Data were
      abstracted from the provincial trauma registry and linked to the hospital
      discharge database. The primary outcome was unplanned readmission to an acute
      care hospital within 30 days of discharge. Candidate risk factors were identified
      by expert consensus and selected for derivation of the risk adjustment model
      using bootstrap resampling. The validity of the QI was evaluated in terms of
      interhospital discrimination, construct validity, and forecasting. RESULTS: The
      risk adjustment model includes patient age, sex, the Injury Severity Score (ISS),
      region of the most severe injury, and 11 comorbid conditions. The QI
      discriminates well across trauma centers (coefficient of variation, 0.02) and is
      correlated with QIs that measure hospital performance in terms of clinical
      processes (r = -0.38), risk-adjusted mortality (r = 0.32), and complication rates
      (r = 0.38). In addition, performance in 2005 to 2007 was predictive of
      performance in 2008 to 2010 (r = 0.59). CONCLUSION: We have developed a QI based
      on risk-adjusted 30-day rates of unplanned readmission, which can be used to
      evaluate trauma care with routinely collected data. The QI is based on a
      comprehensive risk adjustment model with good internal and temporal validity and
      demonstrates good properties in terms of discrimination, construct validity, and
      forecasting. This research represents an essential step toward reducing unplanned
      readmission rates to improve resource use and patient outcomes following injury.
      LEVEL OF EVIDENCE: Prognostic study, level III.

PMID- 24747467
TI  - Randomized controlled trial to evaluate the effectiveness of a video game as a
      child pedestrian educational tool.
AB  - BACKGROUND: Injury is the number one cause of death and disability in children in
      the United States and an increasingly important public health problem globally.
      While prevention of injuries is an important goal, prevention efforts are
      currently fragmented, poorly funded, and rarely studied. Among school-aged
      children, pedestrian crashes are a major mechanism of injury. We hypothesized
      that we could develop a game-based educational tool that would be effective in
      teaching elementary school children the principles of pedestrian safety. METHODS:
      Between November 2011 and June 2013, second- and third-grade children in Los
      Angeles Unified School District were randomly assigned to play a unique
      interactive video game (Ace's Adventure) about pedestrian safety or to a
      traditional didactic session about pedestrian safety. A pretest and posttest were
      administered to the study participants. Afterward, study participants were
      observed for appropriate pedestrian behavior on a simulated street set called
      Street Smarts. All statistical analyses were performed using SAS version 9.2.
      RESULTS: A total of 348 study participants took the pretest and posttest. There
      were 180 who were randomized to the didactic and 168 who were randomized to the
      video game. The didactic group demonstrated a higher mean score increase (1.01, p
      < 0.0001) as compared with the video game group (0.44, p < 0.0001). However,
      observation of study participants revealed that participants who played the video
      game, as compared with the didactic group, more frequently exhibited appropriate
      behavior during the following: exiting a parked car (p = 0.01), signaling to a
      car that was backing up (p = 0.01), signaling to a stopped car (p = 0.0002), and
      crossing the street (p = 0.01). CONCLUSION: Students who played the educational
      video game about pedestrian safety performed similarly to those who attended a
      more traditional and labor-intensive didactic learning. Innovative educational
      methods, such as game playing, could significantly change our approach to injury
      prevention and have the potential to decrease the burden of injury among children
      worldwide.

PMID- 24747468
TI  - The anatomy of an article: title, abstract, and introduction.

PMID- 24747469
TI  - Ultrasound-guided supraclavicular access to the innominate vein for central
      venous cannulation.

PMID- 24747470
TI  - Perioperative supplemental oxygen to reduce surgical site infection: too easy to
      be true.

PMID- 24747471
TI  - Perioperative supplemental oxygen to reduce surgical site infection: too much
      potential to not investigate?

PMID- 24747472
TI  - The trauma safety net hospital under the Affordable Care Act: will it survive?

PMID- 24747473
TI  - Nonoperative management of splenic trauma should be approached with caution in
      the setting of traumatic brain injury.

PMID- 24747474
TI  - Spinal cord injury without radiologic abnormality in children imaged with
      magnetic resonance imaging.

PMID- 24747475
TI  - Driving intoxicated: is hospital admission protective against legal
      ramifications?

PMID- 24747476
TI  - Re: driving intoxicated: is hospital admission protective against legal
      ramifications?

PMID- 24747477
TI  - Early abdominal closure for open abdomens.

PMID- 24747480
TI  - Detection of fluorescent nanoparticle interactions with primary immune cell
      subpopulations by flow cytometry.
AB  - Engineered nanoparticles are endowed with very promising properties for
      therapeutic and diagnostic purposes. This work describes a fast and reliable
      method of analysis by flow cytometry to study nanoparticle interaction with
      immune cells. Primary immune cells can be easily purified from human or mouse
      tissues by antibody-mediated magnetic isolation. In the first instance, the
      different cell populations running in a flow cytometer can be distinguished by
      the forward-scattered light (FSC), which is proportional to cell size, and the
      side-scattered light (SSC), related to cell internal complexity. Furthermore,
      fluorescently labeled antibodies against specific cell surface receptors permit
      the identification of several subpopulations within the same sample. Often, all
      these features vary when cells are boosted by external stimuli that change their
      physiological and morphological state. Here, 50 nm FITC-SiO2 nanoparticles are
      used as a model to identify the internalization of nanostructured materials in
      human blood immune cells. The cell fluorescence and side-scattered light increase
      after incubation with nanoparticles allowed us to define time and concentration
      dependence of nanoparticle-cell interaction. Moreover, such protocol can be
      extended to investigate Rhodamine-SiO2 nanoparticle interaction with primary
      microglia, the central nervous system resident immune cells, isolated from mutant
      mice that specifically express the Green Fluorescent Protein (GFP) in the
      monocyte/macrophage lineage. Finally, flow cytometry data related to nanoparticle
      internalization into the cells have been confirmed by confocal microscopy. 

PMID- 24747482
TI  - Myotropic effects of FMRFamide containing peptides on the heart of the mosquito
      Anopheles gambiae.
AB  - FMRFamide-like peptides (FLPs) are produced by invertebrate and vertebrate
      animals, and regulate diverse physiological processes. In insects, several FLPs
      modulate heart physiology, with some increasing and others decreasing dorsal
      vessel contraction dynamics. Here, we describe the FMRFamide gene structure in
      the mosquito, Anopheles gambiae, quantify the developmental and spatial
      expression of FMRFamide and its putative receptor (FMRFamideR), and show that the
      peptides FMRFamide and SALDKNFMRFamide have complex myotropic properties. RACE
      sequencing showed that the FMRFamide gene encodes eight putative FLPs and is
      alternatively spliced. Of the eight FLPs, only one is shared by A. gambiae, Aedes
      aegypti and Culex quinquefasciatus: SALDKNFMRFamide. Quantitative PCR showed that
      peak expression of FMRFamide and FMRFamideR occurs in second instar larvae and
      around eclosion. In adults, FMRFamide is primarily transcribed in the head and
      thorax, and FMRFamideR is primarily transcribed in the thorax. Intravital video
      imaging of mosquitoes injected FMRFamide and SALDKNFMRFamide revealed that at low
      doses these peptides increase heart contraction rates. At high doses, however,
      these peptides decrease heart contraction rates and alter the proportional
      directionality of heart contractions. Taken altogether, these data describe the
      FMRFamide gene in A. gambiae, and show that FLPs are complex modulators of
      mosquito circulatory physiology. 

PMID- 24747481
TI  - Diffusible gas transmitter signaling in the copepod crustacean Calanus
      finmarchicus: identification of the biosynthetic enzymes of nitric oxide (NO),
      carbon monoxide (CO) and hydrogen sulfide (H2S) using a de novo assembled
      transcriptome.
AB  - Neurochemical signaling is a major component of physiological/behavioral control
      throughout the animal kingdom. Gas transmitters are perhaps the most ancient
      class of molecules used by nervous systems for chemical communication. Three
      gases are generally recognized as being produced by neurons: nitric oxide (NO),
      carbon monoxide (CO) and hydrogen sulfide (H2S). As part of an ongoing effort to
      identify and characterize the neurochemical signaling systems of the copepod
      Calanus finmarchicus, the biomass dominant zooplankton in much of the North
      Atlantic Ocean, we have mined a de novo assembled transcriptome for sequences
      encoding the neuronal biosynthetic enzymes of these gases, i.e. nitric oxide
      synthase (NOS), heme oxygenase (HO) and cystathionine beta-synthase (CBS),
      respectively. Using Drosophila proteins as queries, two NOS-, one HO-, and one
      CBS-encoding transcripts were identified. Reverse BLAST and structural analyses
      of the deduced proteins suggest that each is a true member of its respective
      enzyme family. RNA-Seq data collected from embryos, early nauplii, late nauplii,
      early copepodites, late copepodites and adults revealed the expression of each
      transcript to be stage specific: one NOS restricted primarily to the embryo and
      the other was absent in the embryo but expressed in all other stages, no CBS
      expression in the embryo, but present in all other stages, and HO expressed
      across all developmental stages. Given the importance of gas transmitters in the
      regulatory control of a number of physiological processes, these data open
      opportunities for investigating the roles these proteins play under different
      life-stage and environmental conditions in this ecologically important species. 

PMID- 24747483
TI  - Bioinformatic prediction of Trichoplax adhaerens regulatory peptides.
AB  - Trichoplax adhaerens (phylum Placozoa) is a very simple organism that lacks a
      nervous system. However, its genome contains many genes essential for neuronal
      function and development. I report the results of regulatory peptide predictions
      for this enigmatic animal. Extensive transcriptome, genome, and predicted
      proteome mining allowed us to predict four insulins, at least five short peptide
      precursors, one granulin, one paracrine regulator of cell growth, and one complex
      temptin-attractin pheromone signaling system. The expression of three insulins,
      four short peptide precursors, granulin, and one out of the six temptin genes was
      detected. Five predicted regulatory peptide precursors could potentially release
      over 60 different mature peptides. Some of the predicted peptides are somewhat
      similar to anthozoan RW amides, Aplysia pedal peptide 3, and PRQFV amide. Other
      predicted short peptides could not readily be classified into established
      families. These data provide the foundation for the molecular, biochemical,
      physiological, and behavioral studies of one the most primitive animal
      coordination systems, and give unique insight into the origins and early
      evolution of the nervous system. 

PMID- 24747484
TI  - Salinity and temperature variations reflecting on cellular PCNA, IGF-I and II
      expressions, body growth and muscle cellularity of a freshwater fish larvae.
AB  - The present study assessed the influence of salinity and temperature on body
      growth and on muscle cellularity of Lophiosilurus alexaxdri vitelinic larvae.
      Slightly salted environments negatively influenced body growth of freshwater fish
      larvae and we observed that those conditions notably act as an environmental
      influencer on muscle growth and on local expression of hypertrophia and
      hypeplasia markers (IGFs and PCNA). Furthermore, we could see that salinity
      tolerance for NaCl 4gl(-)(1) diminishes with increasing temperature, evidenced by
      variation in body and muscle growth, and by irregular morphology of the lateral
      skeletal muscle of larvae. We saw that an increase of both PCNA and autocrine IGF
      II are correlated to an increase in fibre numbers and fibre diameter as the
      temperature increases and salinity diminishes. On the other hand, autocrine IGF-I
      follows the opposite way to the other biological parameters assessed, increasing
      as salinity increases and temperature diminishes, showing that this protein did
      not participate in muscle cellularity, but participating in molecular/cellular
      repair. Therefore, slightly salted environments may provide adverse conditions
      that cause some obstacles to somatic growth of this species, suggesting some
      osmotic expenditure with a salinity increment. 

PMID- 24747485
TI  - Nanopodia--thin, fragile membrane projections with roles in cell movement and
      intercellular interactions.
AB  - Adherent cells in culture maintain a polarized state to support movement and
      intercellular interactions. Nanopodia are thin, elongated, largely F-actin
      negative membrane projections in endothelial and cancer cells that can be
      visualized through TM4SF1 (Transmembrane-4-L-six-family-1) immunofluorescence
      staining. TM4SF1 clusters in 100-300 MUm diameter TMED (TM4SF1 enriched
      microdomains) containing 3 to as many as 14 individual TM4SF1 molecules. TMED are
      arranged intermittently along nanopodia at a regular spacing of 1 to 3 TMED per
      MUm and firmly anchor nanopodia to matrix. This enables nanopodia to extend more
      than 100 MUm from the leading front or trailing rear of polarized endothelial or
      tumor cells, and causes membrane residues to be left behind on matrix when the
      cell moves away. TMED and nanopodia have been overlooked because of their extreme
      fragility and sensitivity to temperature. Routine washing and fixation disrupt
      the structure. Nanopodia are preserved by direct fixation in paraformaldehyde
      (PFA) at 37  degrees C, followed by brief exposure to 0.01% Triton X-100 before
      staining. Nanopodia open new vistas in cell biology: they promise to reshape our
      understanding of how cells sense their environment, detect and identify other
      cells at a distance, initiate intercellular interactions at close contact, and of
      the signaling mechanisms involved in movement, proliferation, and cell-cell
      communications. The methods that are developed for studying TM4SF1-derived
      nanopodia may be useful for studies of nanopodia that form in other cell types
      through the agency of classic tetraspanins, notably the ubiquitously expressed
      CD9, CD81, and CD151. 

PMID- 24747486
TI  - Specificity of performance monitoring changes in obsessive-compulsive disorder.
AB  - Obsessive-compulsive disorder (OCD) is characterized by overactivity in frontal
      and striatal brain regions, and event-related potential studies have shown
      increased brain activity during performance monitoring. The error-related
      negativity (ERN) is a component of the event-related potential that is observed
      following incorrect responses, and signals the need for behavioral adjustments.
      ERN enhancements have even been considered as a biomarker or endophenotype of
      OCD. However over the past years, enhanced ERN amplitudes, although less
      reliably, were also found in anxiety and affective disorders. These results
      question the specificity of ERN alterations to OCD. The present review summarizes
      current findings on performance monitoring and feedback processing in OCD and
      their relation to behavioral measures. Further, it discusses possible
      differential mechanisms contributing to amplitude variations in different
      clinical conditions.

PMID- 24747487
TI  - Effects of prenatal stress on fetal and child development: a critical literature
      review.
AB  - Many studies have examined effects of prenatal stress on pregnancy and fetal
      development, especially on prematurity and birthweight, and more recently long
      term effects on child behavioral and emotional development. These studies are
      reviewed and their limitations are discussed with regard to definitions
      (including the concepts of stress and anxiety), stress measurements, samples, and
      control for confounds such as depression. It appears necessary to assess
      individual stress reactivity prospectively and separately at each trimester of
      pregnancy, to discriminate chronic from acute stress, and to take into
      consideration moderator variables such as past life events, sociocultural
      factors, predictability, social support and coping strategies. Furthermore, it
      might be useful to examine simultaneously, during but also after pregnancy,
      stress, anxiety and depression in order to understand better their relationships
      and to evaluate their specific effects on pregnancy and child development.
      Finally, further research could benefit from an integrated psychological and
      biological approach studying together subjective perceived stress and objective
      physiological stress responses in pregnant women, and their effects on fetal and
      child development as well as on mother-infant interactions. 

PMID- 24747488
TI  - Design and methodology of a randomized clinical trial of home-based telemental
      health treatment for U.S. military personnel and veterans with depression.
AB  - Home-based telemental health (TMH) treatments have the potential to address
      current and future health needs of military service members, veterans, and their
      families, especially for those who live in rural or underserved areas. The use of
      home-based TMH treatments to address the behavioral health care needs of U.S.
      military healthcare beneficiaries is not presently considered standard of care in
      the Military Health System. The feasibility, safety, and clinical efficacy of
      home-based TMH treatments must be established before broad dissemination of home
      based treatment programs can be implemented. This paper describes the design,
      methodology, and protocol of a clinical trial that compares in-office to home
      based Behavioral Activation for Depression (BATD) treatment delivered via web
      based video technology for service members and veterans with depression. This
      grant funded three-year randomized clinical trial is being conducted at the
      National Center for Telehealth and Technology at Joint-base Lewis-McChord and at
      the Portland VA Medical Center. Best practice recommendations regarding the
      implementation of in-home telehealth in the military setting as well as the
      cultural and contextual factors of providing in-home care to active duty and
      veteran military populations are also discussed. 

PMID- 24747489
TI  - Mg(2+)- and ATP-dependent inhibition of transient receptor potential melastatin 7
      by oxidative stress.
AB  - Transient receptor potential melastatin 7 (TRPM7) is a Ca(2+)- and Mg(2+)
      permeable nonselective cation channel that contains a unique carboxyl-terminal
      serine/threonine protein kinase domain. It has been reported that reactive oxygen
      species associated with hypoxia or ischemia activate TRPM7 current and then
      induce Ca(2+) overload resulting in neuronal cell death in the brain. In this
      study, we aimed to investigate the molecular mechanisms of TRPM7 regulation by
      hydrogen peroxide (H2O2) using murine TRPM7 expressed in HEK293 cells. Using the
      whole-cell patch-clamp technique, it was revealed that the TRPM7 current was
      inhibited, not activated, by the application of H2O2 to the extracellular
      solution. This inhibition was not reversed after washout or treatment with
      dithiothreitol, suggesting irreversible oxidation of TRPM7 or its regulatory
      factors by H2O2 under whole-cell recording. Application of an electrophile, N
      methylmaleimide (NMM), which covalently modifies cysteine residues in proteins,
      also inhibited TRPM7 current irreversibly. The effects of H2O2 and NMM were
      dependent on free [Mg(2+)]i; the inhibition was stronger when cells were perfused
      with higher free [Mg(2+)]i solutions via pipette. In addition, TRPM7 current was
      not inhibited by H2O2 when millimolar ATP was included in the intracellular
      solution, even in the presence of substantial free [Mg(2+)]i, which is sufficient
      for TRPM7 inhibition by H2O2 in the absence of ATP. Moreover, a kinase-deficient
      mutant of TRPM7 (K1645R) was similarly inhibited by H2O2 just like the wild-type
      TRPM7 in a [Mg(2+)]i- and [ATP]i-dependent manner, indicating no involvement of
      the kinase activity of TRPM7. Thus, these data suggest that oxidative stress
      inhibits TRPM7 current under pathological conditions that accompany intracellular
      ATP depletion and free [Mg(2+)]i elevation. 

PMID- 24747490
TI  - A novel immunomodulatory effect of ugonin U in human neutrophils via stimulation
      of phospholipase C.
AB  - Neutrophils have a crucial role in the immune system and are the first line of
      defense against pathogenic invaders. Neutrophil activation is required for their
      defensive function and can be induced by diverse stimuli, through either binding
      to cell surface receptors or direct intracellular target molecule stimulation. In
      this study, we found that 4"a,5",6",7",8",8"a-hexahydro-5,3',4'-trihydroxy
      5",5",8"a-trimethyl-4H-chromeno [2",3":7,6]flavone (ugonin U), a flavonoid
      isolated from Helminthostachys zeylanica (L) Hook, significantly induced
      superoxide production and release in a time- and concentration-dependent manner.
      A series of experiments was performed to dissect the mechanism of ugonin U
      induced respiratory burst in human neutrophils. Our results demonstrated that
      ugonin U induced a slow increase in intracellular Ca(2+), which was necessary for
      ugonin U-stimulated superoxide release. Use of a formyl peptide receptor (FPR)
      blocker, G protein inhibitor, and protein tyrosine kinase (PTK) inhibitor proved
      that FPR, G proteins, and PTKs were not associated with ugonin U-induced
      respiratory burst. Additionally, immunoblotting results revealed that ugonin U
      did not affect the phosphorylation of mitogen-activated protein kinases and
      protein tyrosine. Nevertheless, a phospholipase C (PLC) inhibitor and an inositol
      triphosphate (IP3) receptor antagonist considerably suppressed ugonin U
      stimulated Ca(2+) mobilization and subsequent superoxide release. Ugonin U also
      induced an increase in intracellular IP3 formation, which could be blocked using
      a PLC inhibitor. In conclusion, our study reveals that ugonin U represents the
      first identified natural flavonoid compound to directly stimulate PLC. Moreover,
      ugonin U induces respiratory burst via the PLC/IP3/Ca(2+) pathway in human
      neutrophils. 

PMID- 24747491
TI  - The role of gerontology in the era of a super-aged society.

PMID- 24747492
TI  - Research perspectives of biomedical gerontology and brain aging research:
      longevity genes in the brain.

PMID- 24747493
TI  - Role of oral health care service in aging society--importance of oral function
      management-.

PMID- 24747494
TI  - Approach to healthy longevity as a target of geriatric medicine.

PMID- 24747496
TI  - Social security reform and the community based integrated care system--what we
      expect for care management-.

PMID- 24747495
TI  - Interdisciplinary approach of studying healthy aging and longevity based on the
      social gerontology.

PMID- 24747497
TI  - Deployment of new gerontological nursing.

PMID- 24747498
TI  - Health care developments to achieve healthy aging and longevity in super-aged
      society.

PMID- 24747499
TI  - The role of health care toward healthy longevity: life style and social
      relationship among community-dwelling elderly people in Japan.

PMID- 24747500
TI  - Progress in gerontechnology for assisting a super-aged society.
AB  - AIM: This paper aims to describe and discuss strategies for the advancement of
      "gerontechnology," a concept that is useful for solving problems in a super-aged
      society. METHODS: The term "gerontechnology" is a combination of "gerontology"
      and "technology" that refers to the fusion of the science of aging and
      engineering. In this paper, a survey of market size, information technology for
      persons with cognitive disabilities, personal mobility technology and universal
      design was conducted. In addition, strategies for advancing gerontechnology are
      discussed. RESULTS: The market for assistive products is approximately 1.2
      trillion yen, while that for universal design products is approximately 3.6
      trillion yen. Information technology improves the capacity for independent living
      among individuals with dementia. There is a project underway to develop a
      communication robot to provide important information to patients. Pill reminders
      and locators are also useful tools based on field tests of Japanese patients.
      Robot technology improves the development of personal mobility devices, which are
      useful for the elderly. The number of universal design products is increasing.
      Assessing the function of the elderly using ergonomics and standardized protocols
      improves these products. CONCLUSIONS: Technology to assist the elderly is
      improving. In order to advance the concept of gerontechnology, the promotion of
      field-based innovation, that is user- and usage field-centered concepts, is
      important.

PMID- 24747501
TI  - Re-building community solidarity in the super aged society.

PMID- 24747502
TI  - Health-related QOL and self-efficacy for activities of daily living in elderly
      residents of mountainous areas with kyphosis: a one-year longitudinal study.
AB  - AIM: The purpose of this study was to investigate changes over one year in the
      prevalence of kyphosis, the ability to perform activities of daily living and
      self-efficacy among elderly residents of mountainous areas. METHODS: The subjects
      included 155 elderly residents of mountainous areas (68 males, 87 females) aged
      65 or older who participated in both our initial and follow-up investigations.
      The investigations were conducted via interviews using questionnaires and the
      index of kyphosis (I/K). The subjects were divided into three groups (non
      kyphosis, kyphosis without changes, kyphosis with worsening) according to the
      change in I/K. RESULTS: The average patient age was 74.9+/-6.2 years. The average
      I/K on the initial investigation was 10.0+/-3.7 (2.4-20.0). On the follow-up
      investigation, the average I/K increased slightly to 10.2+/-3.6 (3.0-22.9). A
      particularly large number of females 65 to 69 years of age exhibited an increase
      in the I/K. The percentage of subjects with an I/K of 13.0 or above was 20.6%.
      The male kyphosis sufferers demonstrated a significant decrease in the health
      related QOL categories of "able to fulfill everyday life roles (physical)" and
      "able to fulfill everyday life roles (mental)." There were no significant
      differences between the females with and without kyphosis. One year later, there
      were significant differences between the three groups in terms of the health
      related QOL categories of "vitality" and "ability to live in society."
      CONCLUSIONS: Female kyphosis sufferers are affected by psychological factors.
      Kyphosis should be detected early and carefully followed up in elderly patients
      in order to prevent the need for nursing care, and appropriately estimating the
      patient's physical condition is required to prevent a decline in the lower limb
      function.

PMID- 24747503
TI  - Factors associated with the level of disability in elderly adults based on the
      Japanese long-term care insurance system.
AB  - AIM: The aim of this study was to identify factors associated with the level of
      disability in elderly adults based on the Japanese long-term care insurance
      system. METHODS: The participants included 3,198 frail elderly subjects (mean
      age: 82.0+/-6.45). The slightly disabled group, with a support level in the long
      term care insurance system, comprised 1,129 elderly adults, and the moderately
      disabled group, with a care level of 1 or 2 in the long-term care insurance
      system, comprised 2,208 elderly adults who received day-care services. The
      following parameters were evaluated: grip strength, chair stand test 5-times
      (CST), one-leg standing with eyes open (OLS), timed "up & go" (TUG), walking
      speed, the mental status questionnaire (MSQ) score and functional independence
      measures (FIM). The participants were categorized into two groups based on the 13
      motor subscales of the FIM (FIM-M): the activity of daily living (ADL)
      independent group, who scored 6 points or higher on all ADL measurements, and the
      ADL care need group, who scored 5 points or under on at least one item in all ADL
      measurements. A multiple logistic regression analysis was used to examine the
      relationships between the long-term care insurance level and the potential
      correlates. RESULTS: The multiple logistic regression model indicated that
      gender, grip strength and the MSQ and FIM-M scores were significantly associated
      with the long-term care insurance level (p<0.05). The FIM-M score exhibited a
      particularly strong correlation with the type of long-term care required (odds
      ratio: 2.47, 95% confidence interval: 1.89-3.24). CONCLUSIONS: The Japanese long
      term care insurance level is associated with physical performance, the cognitive
      function and the ability to perform ADL's. These results suggest that
      comprehensive assessments are useful for understanding the impact of the long
      term care insurance level in elderly adults.

PMID- 24747504
TI  - Tolerability and efficacy of the long-term administration of memantine
      hydrochloride (Memary(r)) in patients with moderate to severe Alzheimer's
      disease.
AB  - AIM: Memantine hydrochloride (Memary(r)), launched in June 2011 in Japan, is used
      in patients with moderate to severe Alzheimer's disease. We performed an
      integrated analysis of data obtained from different clinical studies of memantine
      hydrochloride conducted between 2002 and 2011 in Japan in order to examine the
      long-term tolerability and efficacy of this drug at a dose of 20 mg/day. METHODS:
      Using clinical studies of memantine hydrochloride performed in Japan between 2002
      and 2011, the therapeutic safety and the time course of MMSE scores in 702
      subjects who had received memantine hydrochloride were examined. RESULTS: The
      mean duration of memantine treatment was 798.1 days, with the longest duration of
      3,373 days (approximately nine years and two months). The incidence of adverse
      events every 52 weeks of treatment ranged from 71.0% to 88.9%, and the incidence
      of adverse drug reactions ranged from 5.6% to 32.1%, with no associations between
      the incidence of adverse events and the treatment duration. There were no adverse
      drug reactions specific to the long-term administration of this drug. The
      occurrence of "adverse events" was the primary reason for drug discontinuation.
      During the long-term study observation period, there were many cases of adverse
      events and treatment discontinuation due to the background factors of the
      subjects, including adverse events associated with aging and progression of the
      underlying conditions. In addition, treatment discontinuation was also associated
      with admission to a nursing home or facility due to changes in home nursing care.
      The degree of MMSE score reduction over time was lower in the patients treated
      with memantine than the expected MMSE score reduction observed in the untreated
      patients. CONCLUSIONS: Based on these findings, there are no issues regarding the
      tolerability of memantine hydrochloride administered at a dose of 20 mg/day over
      the long term. Considering changes in the MMSE score, the results indicated that
      memantine hydrochloride may inhibit worsening of the cognitive function for long
      periods of time in patients with Alzheimer's disease.

PMID- 24747505
TI  - Efficacy of intranasal desmopressin for the treatment of nocturnal polyuria in
      the elderly females.
AB  - Older adults often complain of nocturia as one of the most bothersome symptoms of
      lower urinary tract incontinence. Nocturia places such patients at risk of
      falling down and insomnia and increases the care burden. The causes of nocturia
      include various factors, such as neuropathic bladder, prostate hyperplasia and
      pelvic floor muscle weakness. It has also been reported that nocturia is caused
      by an increased renal blood flow while lying down and the loss of diurnal
      variation in vasopressin. The intranasal administration of desmopressin at night
      may improve nocturia. We experienced a case of severe nocturia that could not be
      controlled with fluid restriction, urethral catheterization before sleep or
      anticholinergic drugs. Due to frequent urination during the night, the patient
      was unable to sleep well and required frequent nursing care. Following the
      administration of nasal desmopressin before sleep, the number of episodes of
      nocturia considerably improved. In addition, no adverse events, such as
      hyponatremia, were observed with desmopressin use. Physicians should therefore
      consider using desmopressin in cases with treatment-resistant nocturia.

PMID- 24747506
TI  - Guidance statement on appropriate medical services for the elderly by the study
      group of the Ministry of Health, Labour and Welfare.

PMID- 24747507
TI  - Home end-of-life care for elderly from the point of view of multidisciplinary
      teams.

PMID- 24747511
TI  - Updating emotional content in working memory: a depression-specific deficit?
AB  - BACKGROUND AND OBJECTIVES: Interference from irrelevant negative material might
      be a key mechanism underlying intrusive ruminative thoughts in depression.
      Considering commonalities between depression and social anxiety and the presence
      of similar intrusive thoughts in social anxiety, the current study was designed
      to assess whether interference from irrelevant material in working memory is
      specific to depression or is also present in social anxiety disorder. METHODS: To
      examine the effects of irrelevant emotional material on working memory
      performance, participants memorized two lists of words on each trial and were
      subsequently instructed to ignore one of the lists. Participants were then asked
      to indicate whether a probe word belonged to the relevant list or not. RESULTS:
      Compared to control and social anxiety groups, the depression groups (both pure
      and comorbid with social anxiety disorder) exhibited greater difficulties
      removing irrelevant emotional material from working memory (i.e., greater
      intrusion effects). Greater intrusion effects were also associated with increased
      rumination. LIMITATIONS: Although we included three clinical groups (depression,
      social anxiety, and the comorbid groups), the results are based on a relatively
      small number of participants. CONCLUSIONS: The results indicate that difficulties
      removing irrelevant material from working memory might be unique to depression,
      and the ability to inhibit irrelevant information is relatively preserved in
      social anxiety disorder.

PMID- 24747512
TI  - Plant sterols from foods in inflammation and risk of cardiovascular disease: a
      real threat?
AB  - High dietary intakes of cholesterol together with sedentary habits have been
      identified as major contributors to atherosclerosis. The latter has long been
      considered a cholesterol storage disease; however, today atherosclerosis is
      considered a more complex disease in which both innate and adaptive immune
      inflammatory mechanisms as well as bacteria play a major role, in addition to
      interactions between the arterial wall and blood components. This scenario has
      promoted nutritional recommendations to enrich different type of foods with plant
      sterols (PS) because of their cholesterol-lowering effects. In addition to
      cholesterol, PS can also be oxidized during food processing or storage, and the
      oxidized derivatives, known as phytosterol oxidation products (POPs), can make an
      important contribution to the negative effects of both cholesterol and
      cholesterol oxidation oxides (COPs) in relation to inflammatory disease onset and
      the development of atherosclerosis. Most current research efforts have focused on
      COPs, and evaluations of the particular role and physiopathological implications
      of specific POPs have been only inferential. Appreciation of the inflammatory
      role described for both COPs and POPs derived from foods also provides additional
      reasons for safety studies after long-term consumption of PS. The balance and
      relevance for health of all these effects deserves further studies in humans.
      This review summarizes current knowledge about the presence of sterol oxidation
      products (SOPs) in foods and their potential role in inflammatory process and
      cardiovascular disease. 

PMID- 24747513
TI  - The association between aerobic fitness and language processing in children:
      implications for academic achievement.
AB  - Event-related brain potentials (ERPs) have been instrumental for discerning the
      relationship between children's aerobic fitness and aspects of cognition, yet
      language processing remains unexplored. ERPs linked to the processing of semantic
      information (the N400) and the analysis of language structure (the P600) were
      recorded from higher and lower aerobically fit children as they read normal
      sentences and those containing semantic or syntactic violations. Results revealed
      that higher fit children exhibited greater N400 amplitude and shorter latency
      across all sentence types, and a larger P600 effect for syntactic violations.
      Such findings suggest that higher fitness may be associated with a richer network
      of words and their meanings, and a greater ability to detect and/or repair
      syntactic errors. The current findings extend previous ERP research explicating
      the cognitive benefits associated with greater aerobic fitness in children and
      may have important implications for learning and academic performance. 

PMID- 24747514
TI  - Framing deductive reasoning with emotional content: an fMRI study.
AB  - In the literature concerning the study of emotional effect on cognition, several
      researches highlight the mechanisms of reasoning ability and the influence of
      emotions on this ability. However, up to now, no neuroimaging study was
      specifically devised to directly compare the influence on reasoning performance
      of visual task-unrelated with semantic task-related emotional information. In the
      present functional fMRI study, we devised a novel paradigm in which emotionally
      negative vs. neutral visual stimuli (context) were used as primes, followed by
      syllogisms composed of propositions with emotionally negative vs. neutral
      contents respectively. Participants, in the MR scanner, were asked to assess the
      logical validity of the syllogisms. We have therefore manipulated the emotional
      state and arousal induced by the visual prime as well as the emotional
      interference exerted by the syllogism content. fMRI data indicated a medial
      prefrontal cortex deactivation and lateral/dorsolateral prefrontal cortex
      activation in conditions with negative context. Furthermore, a
      lateral/dorsolateral prefrontal cortex modulation caused by syllogism content was
      observed. Finally, behavioral data confirmed the influence of emotional task
      related stimuli on reasoning ability, since the performance was worse in
      conditions with syllogisms involving negative emotions. Therefore, on the basis
      of these data, we conclude that emotional states can impair the performance in
      reasoning tasks by means of the delayed general reactivity, whereas the emotional
      content of the target may require a larger amount of top-down resources to be
      processed. 

PMID- 24747516
TI  - Digenic/multilocus aetiology of multiple self-healing squamous epithelioma
      (Ferguson-Smith disease): TGFBR1 and a second linked locus.
AB  - Multiple self-healing squamous epithelioma (MSSE) is a rare familial skin cancer
      in which multiple tumours resembling crateriform squamous carcinomas are locally
      invasive but regress spontaneously after several months, leaving deep disfiguring
      facial scars and shallower scars on the limbs. First identified in a number of
      Scottish families, the condition has since been reported more widely. We review
      here the investigations leading to the discovery of loss of function mutations in
      TGFBR1 that are responsible for the disease. Loss of heterozygosity in tumours
      reveals that TGFBR1 acts as a tumour suppressor gene. TGFBR1 was initially
      excluded as the MSSE gene because it lies outside an extensive chromosome 9
      haplotype shared by Scottish families. MSSE can now be regarded as a
      digenic/multilocus disease in view of the evidence of a second linked locus
      necessary for pathogenesis located within the Scottish haplotype. This article is
      part of a Directed Issue entitled: Rare Cancers. 

PMID- 24747515
TI  - Polymerase I and transcript release factor acts as an essential modulator of
      glioblastoma chemoresistance.
AB  - OBJECTIVES: This study is to investigate if polymerase I and transcript release
      factor (PTRF) acts as a modulator in glioblastoma (GBM) chemoresistance. METHODS:
      Multidrug resistant (MDR) GBM cell line U251AR was established by exposing the
      U251 cell line to imatinib. The 2D-DIGE and MALDI-TOF/TOF-MS were performed on
      U251 and U251AR cell lines to screen MDR-related proteins. The expression of PTRF
      was determined by Western blot and quantitative RT-PCR analyses. RESULTS: When
      compared with the parental U251 cells, expression of 21 proteins was
      significantly altered in U251AR cells. Among the 21 differentially expressed
      proteins, the expression of PTRF was up-regulated by 2.14 folds in U251AR cells
      when compared with that in the parental U251 cells. Knockdown of PTRF in GBM cell
      lines significantly increased chemosensitivity of cells to various chemical drugs
      and decreased the expression levels of caveolin1, a major structural component of
      caveolae. Expression levels of PTRF and caveolin1 were significantly up-regulated
      in the relapsed GBM patients. The mRNA level of PTRF and caveolin1 showed a
      positive correlation in the same GBM specimens. CONCLUSIONS: Our results indicate
      that PTRF acts as a modulator in GBM chemoresistance.

PMID- 24747518
TI  - Alternative method for determination of contaminated heparin using chiral
      recognition.
AB  - Since 2008 a significant amount of work has focused on the development of methods
      to analyze contaminated heparin. This work focuses on utilizing heparin's ability
      to serve as a chiral selector as a means for determining contamination.
      Specifically, the effect of contamination on the separation of pheniramine and
      chloroquine enantiomers was explored. Separations were conducted using heparin
      contaminated with chondroitin sulfate at varying levels. For each pair of
      enantiomers, electrophoretic mobility and resolution were calculated. For
      pheniramine enantiomers, an increase in contamination leads to a decrease in the
      electrophoretic mobility and resolution. A linear relationship between
      contamination level and electrophoretic mobility of the pheniramine enantiomers
      was observed for the entire contamination range. A linear relationship was also
      found between contamination level and resolution of the enantiomers between 0 and
      70 percent contamination. For the separation of chloroquine enantiomers, it was
      found that at low levels of contamination, the resolution of enantiomers was
      increased due to the secondary interaction between the chloroquine enantiomers
      and the chondroitin sulfate. Results of this study illustrate the potential of
      using chiral recognition as a means to determine heparin contamination as well as
      the improvement of the chiral resolution of chloroquine with the additional of
      low levels of chondroitin sulfate A. 

PMID- 24747517
TI  - Ghrelin protects against renal damages induced by angiotensin-II via an
      antioxidative stress mechanism in mice.
AB  - We explored the renal protective effects by a gut peptide, Ghrelin. Daily
      peritoneal injection with Ghrelin ameliorated renal damages in continuously
      angiotensin II (AngII)-infused C57BL/6 mice as assessed by urinary excretion of
      protein and renal tubular markers. AngII-induced increase in reactive oxygen
      species (ROS) levels and senescent changes were attenuated by Ghrelin. Ghrelin
      also inhibited AngII-induced upregulations of transforming growth factor-beta
      (TGF-beta) and plasminogen activator inhibitor-1 (PAI-1), ameliorating renal
      fibrotic changes. These effects were accompanied by concomitant increase in
      mitochondria uncoupling protein, UCP2 as well as in a key regulator of
      mitochondria biosynthesis, PGC1alpha. In renal proximal cell line, HK-2 cells,
      Ghrelin reduced mitochondria membrane potential and mitochondria-derived ROS. The
      transfection of UCP2 siRNA abolished the decrease in mitochondria-derived ROS by
      Ghrelin. Ghrelin ameliorated AngII-induced renal tubular cell senescent changes
      and AngII-induced TGF-beta and PAI-1 expressions. Finally, Ghrelin receptor,
      growth hormone secretagogue receptor (GHSR)-null mice exhibited an increase in
      tubular damages, renal ROS levels, renal senescent changes and fibrosis
      complicated with renal dysfunction. GHSR-null mice harbored elongated
      mitochondria in the proximal tubules. In conclusion, Ghrelin suppressed AngII
      induced renal damages through its UCP2 dependent anti-oxidative stress effect and
      mitochondria maintenance. Ghrelin/GHSR pathway played an important role in the
      maintenance of ROS levels in the kidney. 

PMID- 24747519
TI  - Determination of bevantolol in human plasma using liquid chromatography
      electrospray ionization tandem mass spectrometry and its application to a
      bioequivalence study.
AB  - A liquid chromatography-electrospray ionization tandem mass spectrometry method
      was established and validated for the determination of bevantolol in human plasma
      using propranolol as the internal standard. The optimal chromatographic behavior
      of bevantolol and propranolol was achieved on a Welch Ultimate XB-C18 column (5
      MUm, 150 mm * 2.1mm, Maryland, USA) with a mobile phase of acetonitrile-water
      (40:60, v/v) containing 10mM ammonium acetate and 0.1% formic acid. The mass
      spectrometer was operated in selected reaction monitoring mode using the
      transition m/z 346.1>165.1 for bevantolol and m/z 260.3>116.1 for propranolol.
      Sample preparation was carried out through protein precipitation with
      acetonitrile. The calibration curves were linear over the range of 5.00-1,000
      ng/ml. The intra- and inter-day precisions were less than 6.7% and 6.6%,
      respectively. This method was successfully applied to the bioequivalence study of
      two kinds of bevantolol hydrochloride tablets in 24 Chinese male volunteers in
      fasting and postprandial experiment.

PMID- 24747520
TI  - Determination of asperosaponin VI and its active metabolite hederagenin in rat
      tissues by LC-MS/MS: application to a tissue distribution study.
AB  - Two high-performance liquid chromatography (HPLC) coupled with electrospray
      ionization (ESI) mass spectrometry methods were developed and validated for the
      simultaneous determination of asperosaponin VI (A-VI) and hederagenin (HG) in
      rats' various tissues. Biological samples were processed with methanol
      extraction, and glycyrrhetinic acid was chosen as the internal standard (IS). The
      analytes were separated on a C18 column with two gradient elution programs for
      different rat tissue samples. The MS/MS detection was carried out by monitoring
      the transitions of m/z [MH](-) 927.5->603.4 for A-VI, m/z [MH](-) 471.3->471.3
      for HG and m/z [MH](-) 469.4->425.4 for the IS, respectively. The lower limits of
      quantification (LLOQ) for the two analytes in different rat tissues were 2
      6ng/mL, respectively. The methods were successfully applied to a tissue
      distribution study of A-VI and its active metabolite HG in rats. The results of
      the tissue distribution study showed that the highest concentration of A-VI was
      in the gastrointestinal (GI) tract. Besides, A-VI was mainly distributed in lung,
      liver, fat and ovary. HG was almost undetectable in most tissues except for the
      GI tract.

PMID- 24747521
TI  - Development of a dynamic multiple reaction monitoring method for determination of
      digoxin and six active components of Ginkgo biloba leaf extract in rat plasma.
AB  - A new liquid chromatography-tandem mass spectrometry (LC-MS/MS) method by using
      dynamic multiple reaction monitoring (DMRM) has been developed and validated for
      the simultaneous determination of digoxin (DGX) and six main components of Ginkgo
      biloba leaf extract (GBE) in rat plasma. Comparing with the conventional multiple
      reaction monitoring (MRM), DMRM dramatically decreases the number of concurrent
      MRM transitions, and significantly extended the dwell time, which provided much
      higher sensitivity and reproducibility than MRM when complex multi-component
      samples were quantified. The plasma samples were protein precipitated with
      methanol, the detection was accomplished with electro-spray ionization (ESI) as
      the ion source operating in the negative ionization mode, with methanol and water
      as mobile phase, and with an Agilent Zorbax eclipse plus C18 column (4.6 * 100
      mm, 3.5 MUm) as the analytical column. The total run time was 12.0 min. The
      validation of the method was implemented including specificity, linearity,
      accuracy, precision, recovery, matrix effect and stability. This method was
      successfully applied to the herb-drug pharmacokinetic interaction study of DGX
      combined with GBE after oral administration to rats. The result indicated that co
      administration of GBE and DGX significantly influenced the pharmacokinetics of
      DGX when compared to that of single DGX-treated rats.

PMID- 24747522
TI  - Small molecule adduct formation with the components of the mobile phase as a way
      to analyse valproic acid in human serum with liquid chromatography-tandem mass
      spectrometry.
AB  - A valproic acid (VPA) LC-MS/MS analytical method using analyte adduct formation
      was developed and validated in human serum. The fragmentation of the sodium
      acetate adduct (mass transition: 225/143) and acetic acid adduct (mass
      transition: 203/143) were used as the target and qualifier mass transition,
      respectively. A Luna 5 MUm C18 (2) 100 A, 150 mm*2 mm analytical column and a
      mobile phase consisting of A (H2O/methanol=95/5, v/v) and B (H2O/methanol=3/97,
      v/v), both with 10mM ammonium acetate and 0.1% acetic acid (pH=3.2) were used. A
      binary flow pumping mode with a total flow rate of 0.4 mL/min was applied.
      Protein precipitation with 1 mL of the mobile phase B was used as sample
      preparation. The calculated limit of detection/quantification was 0.45/1.0 MUg/mL
      and the inter-/intra-day precision was <6%. The application of a deuterated
      internal standard resulted in a good adduct formation reproducibility. The
      strategy applied made the VPA LC-MS/MS analysis in human serum on the basis of
      two mass transitions possible. Therefore, it is an interesting alternative for
      the VPA pseudo multiple reaction monitoring methods (mass transition 143/143) and
      a proof that the developed strategy is also useful for the analysis of compounds
      which do not produce any stable ion fragments detectable by tandem mass
      spectrometry.

PMID- 24747523
TI  - Dye-attached cryogels for reversible alcohol dehydrogenase immobilization.
AB  - In this work, poly(HEMA-co-GMA) cryogel was synthesized by using
      cryopolymerization technique and this cryogel was functionalized with Cibacron
      Blue F3GA dye. Prepared dye attached cryogel was used for the reversible
      immobilization of alcohol dehydrogenase from its aqueous solution. Cibacron Blue
      F3GA attached poly(HEMA-co-GMA) cryogel was characterized by environmental
      scanning electron microscopy (ESEM), energy dispersive X-ray (EDX) analysis and
      swelling studies. Surface morphology of the cryogel was considerably porous and
      the pore size was found to be around 30-50 MUm. Effects of medium pH, initial
      alcohol dehydrogenase concentration, medium temperature and ionic strength on the
      alcohol dehydrogenase adsorption were also investigated and maximum alcohol
      dehydrogenase adsorption onto the dye-attached cryogel was found to be 8.55 mg/g
      cryogel. Adsorbed alcohol dehydrogenase was desorbed from the cryogel by using 10
      mL of NaCl solution (1.0M; in pH 4.0 acetate buffer). Synthesized cryogel was
      able to reuse for 25 sequential cycles and it was found that, there was no
      negligible decrease in the adsorption capacity of the dye-attached cryogel.

PMID- 24747524
TI  - Metabonomic analysis of the toxic effects of TM208 in rat urine by HPLC-ESI-IT
      TOF/MS.
AB  - 4-Methylpiperazine-1-carbodithiocacid-3-cyano-3,3-diphenylpropyl ester
      hydrochloride (TM208) was a potential antitumor new drug with many preliminary
      studies in pharmacokinetics and pharmacodynamics. This study aims to determine
      whether TM208 elicits toxic effects by metabonomics for the first time. Sprague
      Dawley (SD) rats were exposured to TM208 at a single therapeutic dose
      (100mg/kg/d) for 5 days, metabolites of urine samples from both control and TM208
      treated groups were analyzed using high performance liquid chromatography
      electrospray ionization source in combination with hybrid ion trap and high
      resolution time-of-flight mass spectrometry (HPLC-ESI-IT-TOF/MS). Metabolites
      such as aminoadipic acid, creatine, gluconic acid, cis-aconitic acid, succinic
      acid and pipecolic acid which changed significantly, were identified as potential
      biomarkers. These results suggest that the changes in urinary metabolites of rats
      after exposure to TM208 were mainly related to energy metabolism and amino acid
      metabolism, which may be helpful to further understand the mechanism of TM208
      toxicity in rats and a new drug development.

PMID- 24747525
TI  - Modular analysis of hipposin, a histone-derived antimicrobial peptide consisting
      of membrane translocating and membrane permeabilizing fragments.
AB  - Antimicrobial peptides continue to garner attention as potential alternatives to
      conventional antibiotics. Hipposin is a histone-derived antimicrobial peptide
      (HDAP) previously isolated from Atlantic halibut. Though potent against bacteria,
      its antibacterial mechanism had not been characterized. The mechanism of this
      peptide is particularly interesting to consider since the full hipposin sequence
      contains the sequences of parasin and buforin II (BF2), two other known
      antimicrobial peptides that act via different antibacterial mechanisms. While
      parasin kills bacteria by inducing membrane permeabilization, buforin II enters
      cells without causing significant membrane disruption, harming bacteria through
      interactions with intracellular nucleic acids. In this study, we used a modular
      approach to characterize hipposin and determine the role of the parasin and
      buforin II fragments in the overall hipposin mechanism. Our results show that
      hipposin kills bacteria by inducing membrane permeabilization, and this membrane
      permeabilization is promoted by the presence of the N-terminal domain. Portions
      of hipposin lacking the N-terminal sequence do not cause membrane
      permeabilization and function more similarly to buforin II. We also determined
      that the C-terminal portion of hipposin, HipC, is a cell-penetrating peptide that
      readily enters bacterial cells but has no measurable antimicrobial activity. HipC
      is the first membrane active histone fragment identified that does not kill
      bacterial or eukaryotic cells. Together, these results characterize hipposin and
      provide a useful starting point for considering the activity of chimeric peptides
      made by combining peptides with different antimicrobial mechanisms. This article
      is part of a Special Issue entitled: Interfacially Active Peptides and Proteins.
      Guest Editors: William C. Wimley and Kalina Hristova. 

PMID- 24747526
TI  - How reliable are molecular dynamics simulations of membrane active antimicrobial
      peptides?
AB  - Membrane-active antimicrobial peptides (AMPs) are challenging to study
      experimentally, but relatively easy to investigate using molecular dynamics (MD)
      computer simulations. For this reason, a large number of MD studies of AMPs have
      been reported over recent years. Yet relatively little effort has focused on the
      validity of such simulations. Are these results reliable, and do they agree with
      what is known experimentally? And how much meaningful information can be
      obtained? To answer these questions, we demonstrate here some of the requirements
      and limitations of running MD simulations for several common AMPs: PGLa,
      melittin, maculatin and BP100. The two most important findings are: (a)
      simulation results depend strongly on force field parameters, making experimental
      verification of the simulations obligatory, and (b) slow orientational and
      conformational fluctuations mean that much longer sampling timescales (multi-MUs)
      are needed if quantitative agreement between simulation averages and experimental
      data is to be achieved. This article is part of a Special Issue entitled:
      Interfacially Active Peptides and Proteins. Guest Editors: William C. Wimley and
      Kalina Hristova. 

PMID- 24747527
TI  - Antimicrobial mechanisms: a sponge against fungal infections.
AB  - The finding that the antifungal activity of amphotericin B is primarily due to
      its ability to extract ergosterol from fungal membranes suggests a new rationale
      for drug design, which should lead to advanced treatments, particularly for
      invasive fungal infections.

PMID- 24747528
TI  - Pharmacological chaperones stabilize retromer to limit APP processing.
AB  - Retromer is a multiprotein complex that trafficks cargo out of endosomes. The
      neuronal retromer traffics the amyloid-precursor protein (APP) away from
      endosomes, a site where APP is cleaved into pathogenic fragments in Alzheimer's
      disease. Here we determined whether pharmacological chaperones can enhance
      retromer stability and function. First, we relied on the crystal structures of
      retromer proteins to help identify the 'weak link' of the complex and to complete
      an in silico screen of small molecules predicted to enhance retromer stability.
      Among the hits, an in vitro assay identified one molecule that stabilized
      retromer against thermal denaturation. Second, we turned to cultured hippocampal
      neurons, showing that this small molecule increases the levels of retromer
      proteins, shifts APP away from the endosome, and decreases the pathogenic
      processing of APP. These findings show that pharmacological chaperones can
      enhance the function of a multiprotein complex and may have potential therapeutic
      implications for neurodegenerative diseases. 

PMID- 24747530
TI  - Production of iodine-124 and its applications in nuclear medicine.
AB  - Until recently, iodine-124 was not considered to be an attractive isotope for
      medical applications owing to its complex radioactive decay scheme, which
      includes several high-energy gamma rays. However, its unique chemical properties,
      and convenient half-life of 4.2 days indicated it would be only a matter of time
      for its frequent application to become a reality. The development of new medical
      imaging techniques, especially improvements in the technology of positron
      emission tomography (PET), such as the development of new detectors and signal
      processing electronics, has opened up new prospects for its application. With the
      increasing use of PET in medical oncology, pharmacokinetics, and drug metabolism,
      (124)I-labeled radiopharmaceuticals are now becoming one of the most useful tools
      for PET imaging, and owing to the convenient half-life of I-124, they can be used
      in PET scanners far away from the radionuclide production site. Thus far, the
      limited availability of this radionuclide has been an impediment to its wider
      application in clinical use. For example, sodium [(124)I]-iodide is potentially
      useful for diagnosis and dosimetry in thyroid disease and [(124)I]-M
      iodobenzylguanidine ([(124)I]-MIBG) has enormous potential for use in
      cardiovascular imaging, diagnosis, and dosimetry of malignant diseases such as
      neuroblastoma, paraganglioma, pheochromocytoma, and carcinoids. However, despite
      that potential, both are still not widely used. This is a typical scenario of a
      rising new star among the new PET tracers. 

PMID- 24747529
TI  - C/EBPdelta deficiency sensitizes mice to ionizing radiation-induced hematopoietic
      and intestinal injury.
AB  - Knowledge of the mechanisms involved in the radiation response is critical for
      developing interventions to mitigate radiation-induced injury to normal tissues.
      Exposure to radiation leads to increased oxidative stress, DNA-damage, genomic
      instability and inflammation. The transcription factor CCAAT/enhancer binding
      protein delta (Cebpd; C/EBPdelta is implicated in regulation of these same
      processes, but its role in radiation response is not known. We investigated the
      role of C/EBPdelta in radiation-induced hematopoietic and intestinal injury using
      a Cebpd knockout mouse model. Cebpd-/- mice showed increased lethality at 7.4 and
      8.5 Gy total-body irradiation (TBI), compared to Cebpd+/+ mice. Two weeks after a
      6 Gy dose of TBI, Cebpd-/- mice showed decreased recovery of white blood cells,
      neutrophils, platelets, myeloid cells and bone marrow mononuclear cells,
      decreased colony-forming ability of bone marrow progenitor cells, and increased
      apoptosis of hematopoietic progenitor and stem cells compared to Cebpd+/+
      controls. Cebpd-/- mice exhibited a significant dose-dependent decrease in
      intestinal crypt survival and in plasma citrulline levels compared to Cebpd+/+
      mice after exposure to radiation. This was accompanied by significantly decreased
      expression of gamma-H2AX in Cebpd-/- intestinal crypts and villi at 1 h post-TBI,
      increased mitotic index at 24 h post-TBI, and increase in apoptosis in intestinal
      crypts and stromal cells of Cebpd-/- compared to Cebpd+/+ mice at 4 h post
      irradiation. This study uncovers a novel biological function for C/EBPdelta in
      promoting the response to radiation-induced DNA-damage and in protecting
      hematopoietic and intestinal tissues from radiation-induced injury. 

PMID- 24747531
TI  - Production cross sections of niobium and tantalum isotopes in proton-induced
      reactions on (nat)Zr and (nat)Hf up to 14 MeV.
AB  - Production cross sections of Nb and Ta isotopes in the proton-induced reactions
      on (nat)Zr and (nat)Hf, respectively, were measured up to 14 MeV using a stacked
      foil technique. The observed nuclides in the (nat)Zr(p,x) reactions were
      (90g,91m,92m,95m,95g,96)Nb, (95)Zr, and (87g,88)Y. In the (nat)Hf(p,x) reactions,
      (175,176,177,178,179)Ta and (175)Hf were observed. The obtained cross sections
      for each nuclide were compared with the previously reported data and with the
      theoretical cross sections calculated by the TALYS-1.4 code. Thick-target yields
      of the observed nuclides were deduced from the measured production cross
      sections.

PMID- 24747532
TI  - Loudness perception affected by early age hearing loss.
AB  - Tinnitus and hyperacusis, commonly seen in adults, are also reported in children.
      Although clinical studies found children with tinnitus and hyperacusis often
      suffered from recurrent otitis media, there is no direct study on how temporary
      hearing loss in the early age affects the sound loudness perception. In this
      study, sound loudness changes in rats affected by perforation of the tympanic
      membranes (TM) have been studied using an operant conditioning based behavioral
      task. We detected significant increases of sound loudness and susceptibility to
      audiogenic seizures (AGS) in rats with bilateral TM damage at postnatal 16 days.
      As increase to sound sensitivity is commonly seen in hyperacusis and tinnitus
      patients, these results suggest that early age hearing loss is a high risk factor
      to induce tinnitus and hyperacusis in children. In the TM damaged rats, we also
      detected a reduced expression of GABA receptor delta and alpha6 subunits in the
      inferior colliculus (IC) compared to the controls. Treatment of vigabatrin (60
      mg/kg/day, 7-14 days), an anti-seizure drug that inhibits the catabolism of GABA,
      not only blocked AGS, but also significantly attenuated the loudness response.
      Administration of vigabatrin following the early age TM damage could even prevent
      rats from developing AGS. These results suggest that TM damage at an early age
      may cause a permanent reduction of GABA tonic inhibition which is critical
      towards the maintenance of normal loudness processing of the IC. Increasing GABA
      concentration during the critical period may alleviate the impairment in the
      brain induced by early age hearing loss. 

PMID- 24747533
TI  - Spatial heterogeneity and temporal variations in Echinococcus multilocularis
      infections in wild hosts in a North American urban setting.
AB  - Echinococcus multilocularis, the causative agent of human alveolar
      echinococcosis, has the potential to circulate in urban areas where wild host
      populations and humans coexist. The spatial and temporal distribution of
      infection in wild hosts locally affects the risk of transmission to humans. We
      investigated the spatial and temporal patterns of E. multilocularis infection in
      coyotes and rodent intermediate hosts within the city of Calgary, Canada, and the
      association between spatial variations in coyote infection and the relative
      composition of small mammal assemblages. Infection by E. multilocularis was
      examined in small mammals and coyote faeces collected monthly in five city parks
      from June 2012 to June 2013. Coyote faeces were analysed using a ZnCl(2)
      centrifugation and sedimentation protocol. Infection in intermediate hosts was
      assessed through lethal trapping and post-mortem analysis. Parasite eggs and
      metacestodes were morphologically identified and molecularly confirmed through
      species-specific PCR assays. Of 982 small mammals captured, infection was
      detected in 2/305 (0.66%) deer mice (Peromyscus maniculatus), 2/267 (0.75%)
      meadow voles (Microtus pennsylvanicus), and 1/71 (1.41%) southern red backed
      voles (Myodes gapperi). Overall faecal prevalence in coyotes was 21.42% (n = 385)
      and varied across sites, ranging from 5.34% to 61.48%. Differences in coyote
      faecal prevalence across sites were consistent with local variations in the
      relative abundance of intermediate hosts within the small mammal assemblages.
      Infections peaked in intermediate hosts during autumn (0.68%) and winter (3.33%),
      and in coyotes during spring (43.47%). Peaks of infections in coyote faeces up to
      83.8% in autumn were detected in a hyper-endemic area. To the best of our
      knowledge, our findings represent the first evidence of a sylvatic life-cycle of
      E. multilocularis in a North American urban setting, and provide new insights
      into the complexity of the parasite transmission ecology.

PMID- 24747534
TI  - The Cre/loxP system in Giardia lamblia: genetic manipulations in a binucleate
      tetraploid protozoan.
AB  - The bacteriophage-derived Cre/loxP system is a valuable tool that has
      revolutionised genetic and cell biological research in many organisms. We
      implemented this system in the intestinal parasite Giardia lamblia, an
      evolutionarily diverged protozoan whose binucleate and tetraploid genome
      organisation severely limits the application of reverse genetic approaches. We
      show that Cre-recombinase is functionally expressed in G. lamblia and demonstrate
      "recycling" of selectable markers. Providing the means for more complex and
      versatile genetic modifications, this technique massively increases the scope of
      functional investigations in G. lamblia and other protozoa with similar
      limitations with respect to genetic manipulation. 

PMID- 24747535
TI  - A rapid and specific microplate assay for the determination of intra- and
      extracellular ascorbate in cultured cells.
AB  - Vitamin C (ascorbate) plays numerous important roles in cellular metabolism, many
      of which have only come to light in recent years. For instance, within the brain,
      ascorbate acts in a neuroprotective and neuromodulatory manner that involves
      ascorbate cycling between neurons and vicinal astrocytes--a relationship that
      appears to be crucial for brain ascorbate homeostasis. Additionally, emerging
      evidence strongly suggests that ascorbate has a greatly expanded role in
      regulating cellular and systemic iron metabolism than is classically recognized.
      The increasing recognition of the integral role of ascorbate in normal and
      deregulated cellular and organismal physiology demands a range of medium
      throughput and high-sensitivity analytic techniques that can be executed without
      the need for highly expensive specialist equipment. Here we provide explicit
      instructions for a medium-throughput, specific and relatively inexpensive
      microplate assay for the determination of both intra- and extracellular ascorbate
      in cell culture.

PMID- 24747536
TI  - In vivo performance of a microfabricated catheter for intraparenchymal delivery.
AB  - BACKGROUND: Convection-enhanced delivery (CED) is currently the only effective
      clinical technique to deliver biological therapeutic agents that would otherwise
      not cross the blood-brain barrier. Despite the promise of CED, several technical
      problems have limited its effectiveness. NEW METHOD: Brain infusions into a large
      mammal (pig) were performed with a catheter that was fabricated using micro
      electro-mechanical systems (MEMS) technology (Olbricht et al., 2010). The
      performance of the catheter was evaluated for infusions at increasing infusion
      rates. Magnetic resonance (MR) images were acquired in real time to examine the
      distribution of infused tracers in the parenchyma. RESULTS: Both backflow and the
      distribution of CED of infusates into a variety of cytoarchitectures in porcine
      brain were quantified. Concentration profiles were determined for several MR
      contrast reagents as well as a fluorescent dye that are the sizes of small
      molecules, therapeutic proteins and an adeno-associated virus (AAV). The reagents
      can serve as surrogates for assessing the convective distribution of active
      molecules. Infusion rates up to 20MUL/min were attained without evidence of
      backflow along the catheter. COMPARISON WITH EXISTING METHODS: The device
      performed well in terms of both backflow and infusion, superior to that of many
      studies reported in the literature on other catheters. All infused molecules had
      comparable ratios of distribution to infusion volumes. CONCLUSIONS: The catheter
      described in this report appears able to target tissue structures with precision,
      deliver therapeutics at high infusion rates, and resist backflow that can
      compromise the efficacy of CED therapy. The technology allows development of
      "smart" catheters for future applications.

PMID- 24747537
TI  - Microbial contamination detection in water resources: interest of current optical
      methods, trends and needs in the context of climate change.
AB  - Microbial pollution in aquatic environments is one of the crucial issues with
      regard to the sanitary state of water bodies used for drinking water supply,
      recreational activities and harvesting seafood due to a potential contamination
      by pathogenic bacteria, protozoa or viruses. To address this risk, microbial
      contamination monitoring is usually assessed by turbidity measurements performed
      at drinking water plants. Some recent studies have shown significant correlations
      of microbial contamination with the risk of endemic gastroenteresis. However the
      relevance of turbidimetry may be limited since the presence of colloids in water
      creates interferences with the nephelometric response. Thus there is a need for a
      more relevant, simple and fast indicator for microbial contamination detection in
      water, especially in the perspective of climate change with the increase of heavy
      rainfall events. This review focuses on the one hand on sources, fate and
      behavior of microorganisms in water and factors influencing pathogens' presence,
      transportation and mobilization, and on the second hand, on the existing optical
      methods used for monitoring microbiological risks. Finally, this paper proposes
      new ways of research. 

PMID- 24747538
TI  - Motor vehicle accident eye injuries in northern Israel.
AB  - PURPOSE: To investigate the occurrence and types of motor vehicle accident eye
      trauma in north Israel. METHODS: The records between the years 2007-2011 of the
      Ophthalmology Emergency Room of one medical center were searched. Eye injuries
      due to motor vehicle accidents were classified according to type, severity of
      injury and demographic data of patients. RESULTS: Nearly five percents of ER
      presentations were due to motor vehicle accidents. Most motor vehicle accident
      related eye injuries were mild. CONCLUSION: Efforts should be taken to prevention
      and to minimize the severity of motor vehicle accident-related eye injuries.

PMID- 24747539
TI  - Though not reservoirs, dogs might transmit Leptospira in New Caledonia.
AB  - Leptospira has been a major public health concern in New Caledonia for decades.
      However, few multidisciplinary studies addressing the zoonotic pattern of this
      disease were conducted so far. Here, pig, deer and dog samples were collected.
      Analyses were performed using molecular detection and genotyping. Serological
      analyses were also performed for dogs. Our results suggest that deer are a
      reservoir of L. borgpetersenii Hardjobovis and pigs a reservoir of L. interrogans
      Pomona. Interestingly, 4.4% of dogs were renal carriers of Leptospira. In dog
      populations, MAT results confirmed the circulation of the same Leptospira
      serogroups involved in human cases. Even if not reservoirs, dogs might be of
      significance in human contamination by making an epidemiological link between
      wild or feral reservoirs and humans. Dogs could bring pathogens back home,
      shedding Leptospira via their urine and in turn increasing the risk of human
      contamination. We propose to consider dog as a vector, particularly in rural
      areas where seroprevalence is significantly higher than urban areas. Our results
      highlight the importance of animal health in improving leptospirosis prevention
      in a One Health approach. 

PMID- 24747540
TI  - Behavior of VOCs and carbonyl compounds emission from different types of
      wallpapers in Korea.
AB  - Emissions of volatile organic compounds (VOCs) and carbonyls from three types of
      commercially available wallpapers (i.e., PVC-coated, paper-backed, natural
      material-coated) in Korea were evaluated using a 20 L small chamber. A total of
      332 products were tested for emission factors, frequencies of occurrence and
      composition ratios. Toluene and formaldehyde concentrations were below Korean
      standard values for all products; however, the total VOC (TVOC) concentrations
      exceeded current standards (4.0 mg/m2.h) for 30 products. The TVOC emission
      factor for PVC-coated wallpapers, for which polymer materials are used in the
      manufacturing process, was seven and 16 times higher than those of paper-backed
      and natural material-coated wallpapers, respectively. The detection frequencies
      for toluene and formaldehyde were the highest (82.5%) and fourth highest (79.5%),
      respectively among the 50 target chemical species. The composition ratios for
      BTEX ranged from 0.3% to 5.1% and unidentified VOCs, which were not qualitatively
      analyzed using standard gas methods, ranged from 90.2% to 94.8%. Among six
      carbonyl compounds (acrolein was not detected in any type of wallpaper), acetone
      had the highest concentrations in PVC-coated (44.6%) and paper-backed (66.6%)
      wallpapers. Formaldehyde emissions were highest (64.6%) for natural material
      coated wallpapers, a result of the formaldehyde-based resin used in the
      manufacturing process for these products.

PMID- 24747541
TI  - Occupational exposure to Staphylococcus aureus and Enterococcus spp. among spray
      irrigation workers using reclaimed water.
AB  - As reclaimed water use expands, it is important to evaluate potential
      occupational health risks from exposure to this alternative water source. We
      compared odds of colonization with methicillin-resistant Staphylococcus aureus
      (MRSA), methicillin-susceptible S. aureus (MSSA), vancomycin-resistant
      enterococci (VRE), and vancomycin-susceptible enterococci (VSE) between spray
      irrigation workers using reclaimed water and office worker controls. Nasal and
      dermal swabs from 19 spray irrigation workers and 24 office worker controls were
      collected and analyzed for MRSA, MSSA, VRE, and VSE. Isolates were confirmed
      using standard biochemical tests and polymerase chain reaction assays.
      Antimicrobial susceptibility testing was performed by Sensititre(r) microbroth
      dilution. Data were analyzed by two-sample proportion, chi-square, Fisher's exact
      tests, and logistic regression. No MRSA or VRE were detected in any samples. MSSA
      was detected in 26% and 29% of spray irrigators and controls, respectively. VSE
      was detected in 11% and 0% of spray irrigation workers and controls,
      respectively. The adjusted odds of MSSA, multidrug-resistant MSSA, and either
      MSSA or VSE colonization were greater among spray irrigation workers, however
      results were not statistically significant. Future studies with larger sample
      sizes are needed to further evaluate this relationship. 

PMID- 24747542
TI  - Public Health England's draft report on shale gas extraction.

PMID- 24747543
TI  - Application of ECMO to the treatment of benign double tracheoesophageal fistula:
      report of a case.
AB  - This report presents the extracorporeal membrane oxygenation (ECMO)-assisted
      surgical as a treatment of benign double tracheoesophageal fistula. The patient
      was a 43-year-old woman who presented the airway obstruction for 3 weeks after
      the esophagus metal stent implantation for the tracheoesophageal fistula 1 year
      ago. The airway obstruction was due to the expansion and piercing of the metal
      stent through the upper part of the esophagus into the tracheal cavity. In view
      of the failure of endotracheal intubation, we finally used ECMO-assisted surgery
      to remove the stent. And at the same time, cervical esophagostomy externa,
      exclusion of the thoracic tracheoesophageal fistulas and gastrostomy were
      performed. 

PMID- 24747544
TI  - Can image analysis on high-resolution computed tomography predict non-invasive
      growth in adenocarcinoma of the lung?
AB  - PURPOSE: Preoperative radiological predictions of pathological invasiveness must
      be objective and reproducible in addition to being accurate when considering
      limited surgery for early lung cancer. METHODS: Two cohorts were used for the
      analysis. Two independent observers traced lesion edges and measured areas and
      proportions of solid component on tumor images with the largest diameter by high
      resolution computed tomography images and "Image J" software. RESULTS: The value
      of the intraclass correlation was 0.997 (95% confidence interval [CI], 0.996
      0.998) for the area of solid component and 0.979 (95%CI, 0.958-0.986) for the
      proportion of solid component, suggesting such parameters were reliable in terms
      of reproducibility. Az value was 0.898 (95%CI, 0.842-0.953) for the area of solid
      component and 0.882 (95%CI, 0.816-0.949) for the proportion of solid component,
      demonstrating 2 parameters were both highly predictive of non-invasive
      adenocarcinoma. The optimal prediction of non-invasive adenocarcinoma with a cut
      off value of 7.5 mm(2) for the area of solid component resulted in a sensitivity
      of 85.3% and specificity of 86.2% in Cohort 1 and a sensitivity of 66.7% and
      specificity of 88.5% in Cohort 2. CONCLUSION: Image analysis using "Image J"
      software was promising for predicting non-invasive adenocarcinoma with its
      limited inter-observer variability and high predictive performance.

PMID- 24747545
TI  - Characteristics of cardiac allograft vasculopathy induced by immunomodulation in
      the miniature Swine.
AB  - PURPOSE: We aimed to develop swine cardiac transplantation model for study of
      cardiac allograft vasculopathy (CAV) and to characterize the mechanisms of its
      formation. METHODS: Heterotropic cardiac transplantation was performed in swine
      leukocyte antigen mismatched miniature swine, and CAV was induced by
      immunomodulation by cyclosporine A (CyA). Histology and immunohistochemistry were
      performed to identify cellular components of CAV. Fluorescence in situ
      hybridization (FISH) was developed for detection of 1 and Y-chromosome for
      identification of cell origin in the female donor to the male recipient heart
      transplantation model. RESULTS: CAV was successfully developed by
      immunomodulation of CyA. Severity of CAV revealed more prominent in the distal
      epicardial coronary arteries than proximal coronary arteries. Phenotype of the
      SMCs proliferated in the intimal thickening of CAV were mostly
      embryonal/secretory type. Our new chromosome specific probes for FISH method were
      useful for discrimination of sex of each cell, and proliferated SMCs were
      revealed to be mainly donor origin. CONCLUSION: CAV mimicking human heart
      transplantation can be developed by appropriate immunomodulation in the swine. In
      swine CAV, proliferated SMCs seen in the intimal thickening were demonstrated to
      be from the donor origin.

PMID- 24747546
TI  - Outcomes of lobectomy in 'active' octogenarians with clinical stage I non-small
      cell lung cancer.
AB  - INTRODUCTION: In octogenarians with early stage of lung cancer, sublobar
      resection has been shown to be no inferior survival to lobectomy. However, some
      octogenarians remain physically and mentally active. METHODS: We retrospectively
      studied 65 octogenarians who underwent curative resection for clinical stage I
      NSCLC (excluding adenocarcinoma in situ). All patients were assessed by
      cardiologists and underwent stair-climbing tests (five flights, 18 m) and
      cognitive function tests. Lobectomy was performed in patients who could climb 5
      flights of stairs without stopping or oxygen desaturation of >4%. RESULTS: The
      actuarial survival rate was 68.6% at 5 years, and the median survival time was
      109.2 months. Forty-three patients met the criteria for lobectomy. As compared
      with sublobar resection, lobectomy was associated with significantly higher rates
      of overall survival (78.4% vs. 48.5%; p = 0.02) and disease-specific survival
      (88.4% vs. 61.7%; p = 0.02) at 5 years. On multivariate analysis, male sex
      (hazard ratio, 3.827; 1.382-10.596) and sublobar resection (2.261; 1.054-5.360)
      were independent risk factors for survival. Mental disorders occurred in 6
      patients (9.2%), and their score on preoperative cognitive function tests was
      significantly lower than that of patients without mental disorders (22.7 vs.
      26.0, p <0.01). CONCLUSION: Outcomes of lobectomy are good in physically and
      mentally competent octogenarians.

PMID- 24747547
TI  - The impact of preoperative and postoperative pulmonary hypertension on long-term
      surgical outcome after mitral valve repair for degenerative mitral regurgitation.
AB  - PURPOSE: The aim of this study is to elucidate the impact of preoperative and
      postoperative pulmonary hypertension (PH) on long-term clinical outcomes after
      mitral valve repair for degenerative mitral regurgitation. METHODS: A total of
      654 patients who underwent mitral valve repair for degenerative mitral
      regurgitation between 1991 and 2010 were retrospectively reviewed. Patients were
      divided into PH(+) group (137 patients) and PH(-) group (517 patients). Follow-up
      was complete in 99.0%. The median follow-up duration was 7.5 years. RESULTS:
      Patients in PH(+) group were older, more symptomatic and had higher tricuspid
      regurgitation grade. Thirty-day mortality was not different between 2 groups (p =
      0.975). Long-term survival rate was lower in PH(+) group; 10-year survival rate
      after the operation was 85.2% +/- 4.0% in PH(+) group and 89.7% +/- 1.8% in PH(-)
      group (Log-rank, p = 0.019). The incidence of late cardiac events were not
      different between groups, however, the recurrence of PH was more frequent in
      PH(+) group. The recurrence of PH had an adverse impact on survival rate, late
      cardiac events and symptoms. Univariate analysis showed age and preoperative
      tricuspid regurgitation grade were the predictors of PH recurrence. CONCLUSION:
      Early surgical indication should be advocated for degenerative mitral
      regurgitation before the progression of pulmonary hypertension and tricuspid
      regurgitation.

PMID- 24747548
TI  - Isolated intrapulmonary Castleman's disease: a case report, review of the
      literature.
AB  - Castleman's disease (CD), also known as angiofollicular lymph node hyperplasia,
      is an uncommon, lymphoproliferative disorder of unknown etiology, mostly
      involving the mediastinum. Parenchymal lung involvement of the disease is
      extremely rare. Intrapulmonary CD has been reported in seven cases in the English
      literature. We describe an asymptomatic 28-year-old woman with lesion in the
      chest X-ray. Computed tomography (CT) of the chest confirmed a 5.5 * 5 cm well
      defined, lobulated mass in the hilum of the right upper lobe. She underwent
      surgical resection for diagnosis and treatment. Pathologic examination showed
      hyaline vascular type (Castleman's disease) lymph node hyperplasia. CD rarely
      arises from the intrapulmonary lymph nodes. In these patients, preoperative
      diagnosis is difficult and invasive attempts may be required. 

PMID- 24747549
TI  - Molecular analysis of liquid cytological samples collected by bronchoscopy with
      radial endobronchial ultrasonography and guide sheath.
AB  - A 64-year-old man who underwent sigmoid resection for Stage 4 colon cancer had a
      growing nodule on the left upper lobe during follow-up. Surgical resection
      revealed primary pulmonary adenocarcinoma. Subsequently, a new nodule appeared in
      the contralateral S(1)b, for which endobronchial ultrasonography with a guide
      sheath (EBUS-GS) was performed for diagnosis. However, histopathologic
      examinations were inconclusive. Gene analysis of the liquid samples from this
      lesion revealed KRAS mutation, which on hindsight was not detected in the
      metachronous left upper lobe cancer but was detected in the resected sigmoid
      colon. Hence, the right upper lobe nodule was diagnosed by bronchoscopy as colon
      cancer metastasis, confirmed after wedge resection. For specimen obtained by EBUS
      GS, search for gene mutation in the liquid specimen is useful as an ancillary
      test especially when histological diagnosis is equivocal. Thus, developments on
      diagnostic tools using liquid samples are highly expected in the future. 

PMID- 24747550
TI  - Surgical outcomes of post intubational or post tracheostomy tracheal stenosis:
      report of 18 cases in single institution.
AB  - PURPOSE: Tracheal resection and end-to end anastomosis (TRE) is known as standard
      treatment of tracheal stenosis (TS) and there are various methods to keep
      ventilation during operation. We reviewed ventilation methods and postoperative
      outcomes in patients with postintubational (PI) or posttracheostomy (PT) TS.
      PATIENTS AND METHODS: From May 2006 to May 2013, 18 patients with PI or PTTS
      underwent TRE in our hospital. All patients' records were retrospectively
      reviewed. RESULTS: The mean duration of intubation and tracheostomy were 14.2
      days (range: 2 to 27 days) and 114.9 days (range: 43 to 215 days). The location
      of stenosis was tube cuffs (n = 10), stoma (n = 6) and double stenosis involving
      cuff and stoma (n = 2). The mean diameter of stenotic lesion was 5.4 mm (range: 2
      to 9 mm. ECMO (n = 4) was performed in critical stenosis. Of two cases with
      double stenosis, one underwent preoperative endotracheal balloon dilatation and
      the other underwent TRE with cricoplasty. The overall complication rate was
      11.8%. The mean follow-up duration was 14.0 months (range: 0.9 to 56.3 months).
      CONCLUSION: Comparing with the literatures, TS treated by TRE in our hospital has
      shown satisfactory outcomes. To maintain appropriate ventilation for critical
      stenosis, ECMO could be one of safe methods.

PMID- 24747551
TI  - A calpain-cleaved fragment of beta-catenin promotes BCRABL1+ cell survival evoked
      by autophagy induction in response to imatinib.
AB  - Autophagy protects chronic myeloid leukemia stem cells from tyrosine kinase
      inhibitors hence supporting the disease persistence under therapy. However, the
      signals involved in autophagy regulation relative to BCR-ABL1 are still elusive.
      The autophagic flux proceeding from the inhibition of BCR-ABL1 tyrosine kinase
      represents a regulatory mechanism of beta-catenin stability through events
      encompassing the activation of calpain, which targets beta-catenin for proteasome
      independent degradation. Accordingly, its inactivation may contribute to induce
      autophagy and autophagy induction may, in turn, promote beta-catenin
      autolysosomal degradation to originate a regulatory loop where beta-catenin plays
      a central role in cell decision between life and death. Here we proved that the
      cytoplasmic accumulation of beta-catenin driven by up-regulation of its
      antagonist Chibby1 is a component of autophagy induction in response to imatinib
      in BCR-ABL1+ cells opposing the apoptotic death. It is contingent upon ER stress
      and elevation of free Ca(2+) cytosolic concentration and results in the calpain
      cleavage into a 28kDa fragment implicated in beta-catenin proteasome-independent
      degradation. More important for BCR-ABL1+ cell survival and proliferation
      following IM treatment, might be the calpain-mediated cleavage of beta-catenin
      accumulated within the cytoplasmic compartment into a 75kDa fragment, still
      owning TCF-dependent transcriptional activity. Such a beta-catenin fragment might
      be crucial for BCR-ABL1+ cell survival following the fusion protein TK
      inhibition. 

PMID- 24747552
TI  - Constitutively active NDR1-PIF kinase functions independent of MST1 and hMOB1
      signalling.
AB  - The human MST1/hMOB1/NDR1 tumour suppressor cascade regulates important cellular
      processes, such as centrosome duplication. hMOB1/NDR1 complex formation appears
      to be essential for NDR1 activation by autophosphorylation on Ser281 and
      hydrophobic motif (HM) phosphorylation at Thr444 by MST1. To dissect these
      mechanistic relationships in MST1/hMOB1/NDR signalling, we designed NDR1 variants
      carrying modifications that mimic HM phosphorylation and/or abolish hMOB1/NDR1
      interactions. Significantly, the analyses of these variants revealed that NDR1
      PIF, an NDR1 variant containing the PRK2 hydrophobic motif, remains hyperactive
      independent of hMOB1/NDR1-PIF complex formation. In contrast, as reported for the
      T444A phospho-acceptor mutant, NDR1 versions carrying single phospho-mimicking
      mutations at the HM phosphorylation site, namely T444D or T444E, do not display
      increased kinase activities. Collectively, these observations suggest that in
      cells Thr444 phosphorylation by MST1 depends on the hMOB1/NDR1 association, while
      Ser281 autophosphorylation of NDR1 can occur independently. By testing centrosome
      targeted NDR1 variants in NDR1- or MST1-depleted cells, we further observed that
      centrosome-enriched NDR1-PIF requires neither hMOB1 binding nor MST1 signalling
      to function in centrosome overduplication. Taken together, our biochemical and
      cell biological characterisation of NDR1 versions provides novel unexpected
      insights into the regulatory mechanisms of NDR1 and NDR1's role in centrosome
      duplication. 

PMID- 24747553
TI  - Effects of horizontal vs vertical vaginal cuff closure techniques on vagina
      length after vaginal hysterectomy: a prospective randomized study.
AB  - STUDY OBJECTIVE: To compare the effects of horizontal and vertical vaginal cuff
      closure techniques on vagina length after vaginal hysterectomy. DESIGN:
      Prospective randomized study (Canadian Task Force classification I). SETTING:
      Teaching and research hospital, a tertiary center. PATIENTS: Fifty-two women with
      POP-Q stage 0 or 1 uterine prolapse were randomized into 2 groups using vertical
      (n = 26) or horizontal (n = 26) vaginal cuff closure. INTERVENTIONS: All patients
      underwent vaginal hysterectomy. MEASUREMENTS AND MAIN RESULTS: Vagina length in
      the 2 groups was compared preoperatively, immediately after surgery, and at 6
      weeks postoperatively. Mean (SD) preoperative vagina length in the horizontal and
      vertical groups was similar (7.87 [0.92] cm vs 7.99 [0.78] cm; p = .41).
      Immediately postoperatively, the vagina was significantly shorter in the
      horizontal group than in the vertical group (6.61 [0.89] cm vs 7.51 [0.74] cm; p
      < .001). At 6 weeks postoperatively, the vagina was still significantly shorter
      in the horizontal group (6.55 [0.89] cm vs 7.42 (0.73) cm; p < .001). The mean
      difference in vagina length before and after surgery was also significantly
      higher in the horizontal group than in the vertical group (-1.26 [0.12] cm vs
      0.49 [0.11] cm; p < .001). CONCLUSION: Vertical cuff closure during vaginal
      hysterectomy seems to preserve vagina length better than does horizontal cuff
      closure.

PMID- 24747554
TI  - Exposure to mercury among Spanish preschool children: trend from birth to age
      four.
AB  - The purpose of this study is to describe the total hair mercury concentrations
      and their determinants in preschool Spanish children, as well as to explore the
      trend in mercury exposure from birth to the age four. This evolution has been
      scarcely studied in other birth cohort studies. The study population was 580 four
      year old children participating in the INMA (i.e. Childhood and Environment)
      birth cohort study in Valencia (2008-2009). Total mercury concentration at age
      four was measured in hair samples by atomic absorption spectrometry. Fish
      consumption and other covariates were obtained by questionnaire. Multivariate
      linear regression models were conducted in order to explore the association
      between mercury exposure and fish consumption, socio-demographic characteristics
      and prenatal exposure to mercury. The geometric mean was 1.10 ug/g (95%CI: 1.02,
      1.19). Nineteen percent of children had mercury concentrations above the
      equivalent to the Provisional Tolerable Weekly Intake proposed by WHO. Mercury
      concentration was associated with increasing maternal age, fish consumption and
      cord blood mercury levels, as well as decreasing parity. Children whose mothers
      worked had higher mercury levels than those with non working mothers. Swordfish,
      lean fish and canned fish were the fish categories most associated with hair
      mercury concentrations. We observed a decreasing trend in mercury concentrations
      between birth and age four. In conclusion, the children participating in this
      study had high hair mercury concentrations compared to reported studies on
      children from other European countries and similar to other countries with high
      fish consumption. The INMA study design allows the evaluation of the exposure to
      mercury longitudinally and enables this information to be used for biomonitoring
      purposes and dietary recommendations.

PMID- 24747555
TI  - Combined impact of lead, cadmium, polychlorinated biphenyls and non-chemical risk
      factors on blood pressure in NHANES.
AB  - High blood pressure is associated with exposure to multiple chemical and non
      chemical risk factors, but epidemiological analyses to date have not assessed the
      combined effects of both chemical and non-chemical stressors on human populations
      in the context of cumulative risk assessment. We developed a novel modeling
      approach to evaluate the combined impact of lead, cadmium, polychlorinated
      biphenyls (PCBs), and multiple non-chemical risk factors on four blood pressure
      measures using data for adults aged >= 20 years from the National Health and
      Nutrition Examination Survey (1999-2008). We developed predictive models for
      chemical and other stressors. Structural equation models were applied to account
      for complex associations among predictors of stressors as well as blood pressure.
      Models showed that blood lead, serum PCBs, and established non-chemical stressors
      were significantly associated with blood pressure. Lead was the chemical stressor
      most predictive of diastolic blood pressure and mean arterial pressure, while
      PCBs had a greater influence on systolic blood pressure and pulse pressure, and
      blood cadmium was not a significant predictor of blood pressure. The
      simultaneously fit exposure models explained 34%, 43% and 52% of the variance for
      lead, cadmium and PCBs, respectively. The structural equation models were
      developed using predictors available from public data streams (e.g., U.S.
      Census), which would allow the models to be applied to any U.S. population
      exposed to these multiple stressors in order to identify high risk
      subpopulations, direct intervention strategies, and inform public policy.

PMID- 24747556
TI  - Using an alpha-bungarotoxin binding site tag to study GABA A receptor membrane
      localization and trafficking.
AB  - It is increasingly evident that neurotransmitter receptors, including ionotropic
      GABA A receptors (GABAAR), exhibit highly dynamic trafficking and cell surface
      mobility(1-7). To study receptor cell surface localization and endocytosis, the
      technique described here combines the use of fluorescent alpha-bungarotoxin with
      cells expressing constructs containing an alpha-bungarotoxin (Bgt) binding site
      (BBS). The BBS (WRYYESSLEPYPD) is based on the alpha subunit of the muscle
      nicotinic acetylcholine receptor, which binds Bgt with high affinity(8,9).
      Incorporation of the BBS site allows surface localization and measurements of
      receptor insertion or removal with application of exogenous fluorescent Bgt, as
      previously described in the tracking of GABAA and metabotropic GABAB
      receptors(2,10). In addition to the BBS site, we inserted a pH-sensitive GFP
      (pHGFP(11)) between amino acids 4 and 5 of the mature GABAAR subunit by standard
      molecular biology and PCR cloning strategies (see Figure 1)(12). The BBS is 3' of
      the pH-sensitive GFP reporter, separated by a 13-amino acid alanine/proline
      linker. For trafficking studies described in this publication that are based on
      fixed samples, the pHGFP serves as a reporter of total tagged GABAAR subunit
      protein levels, allowing normalization of the Bgt labeled receptor population to
      total receptor population. This minimizes cell to cell Bgt staining signal
      variability resulting from higher or lower baseline expression of the tagged
      GABAAR subunits. Furthermore the pHGFP tag enables easy identification of
      construct expressing cells for live or fixed imaging experiments. 

PMID- 24747557
TI  - Theoretical insight into the pyrolytic deformylation of levoglucosenone and
      isolevoglucosenone.
AB  - A computational study was conducted to gain insight into the pyrolytic
      deformylations of levoglucosenone and isolevoglucosenone. Present B3LYP/6-31G(*)
      and CBS-QB3 calculations provide valuable evidence to rule out the formation of
      isolevoglucosenone during the pyrolytic degradation of cellulosic materials.
      This, along with the supplementary data herein presented and with other recent
      reports, suggest that levoglucosenone should not be formed directly from
      levoglucosan (as proposed in numerous reports), but rather from another
      intermediate, such as 1,4:3,6-dianhydro-alpha-d-glucopyranose. 

PMID- 24747558
TI  - Effect of zirconia surface treatment on zirconia/veneer interfacial toughness
      evaluated by fracture mechanics method.
AB  - OBJECTIVES: The aim of this study was to evaluate the effect of the airborne
      particle abrasion and liner application on the interfacial toughness between
      veneering porcelain and zirconia core by means of a fracture mechanics test.
      METHODS: Beam-shaped zirconia specimens were sectioned and divided into 4 groups
      according to different surface treatments as follows: Group C (control): no
      treatment; Group L: application of liner; Group A: airborne-particle abrasion
      with Al2O3 (sandblasting); and Group AL: airborne-particle abrasion and
      application of liner. The zirconia surfaces before and after sandblasting were
      observed and analyzed by SEM and white light interferometer. Specimens of each
      pretreated group were veneered with 3 core/veneer thickness ratios of 2:3, 1:1,
      and 3:2, corresponding to 3 phase angles respectively. Fracture mechanics test
      was performed on each specimen, the energy release rate G and phase angle psi
      were calculated to characterize interfacial toughness. The experimental data were
      analyzed statistically using three-way ANOVA and the Tukey's HSD test. The
      surfaces of fractured specimens were examined by SEM and EDX. RESULTS: At each
      phase angle, the interfaces with no treatment had higher mean G values than that
      of other groups. All the specimens showed mixed failure mode with residual veneer
      or liner on the zirconia surfaces. CONCLUSIONS: The toughness of zirconia/veneer
      interface with no treatment is significantly higher than that of interfaces
      subjected to liner application and airborne-particle abrasion. CLINICAL
      SIGNIFICANCE: Liner application and airborne-particle abrasion seem to reduce
      zirconia/veneer interfacial toughness. Therefore, the two surface treatment
      methods should be applied with caution.

PMID- 24747559
TI  - Inflammation in pulmonary hypertension: what we know and what we could logically
      and safely target first.
AB  - Inflammation is important for the initiation and the maintenance of vascular
      remodeling in most of the animal models of pulmonary arterial hypertension (PAH),
      and therapeutic targeting of inflammation in these models blocks PAH development.
      In humans, pulmonary vascular lesions of PAH are the source of cytokine and
      chemokine production, related to inflammatory cell recruitment and lymphoid
      neogenesis. Circulating autoantibodies to endothelial cells and to fibroblasts
      have been reported in 10-40% of patients with idiopathic PAH, suggesting a
      possible role for autoimmunity in the pathogenesis of pulmonary vascular lesions.
      Current specific PAH treatments have immunomodulatory properties, and some
      studies have demonstrated a correlation between levels of circulating
      inflammatory mediators and patient survival. New immunopathological approaches to
      PAH should enable the development of innovative treatments for this severe
      condition. 

PMID- 24747561
TI  - WITHDRAWN: DrugPrinter: print any drug instantly.
AB  - This article has been withdrawn at the request of the author. 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- 24747560
TI  - Thrombosis, platelets, microparticles and PAH: more than a clot.
AB  - Pulmonary arterial hypertension (PAH) is a progressive disease that involves
      pathological remodeling, vasoconstriction and thrombosis. Alterations in
      hemostasis, coagulation and platelet activation are consistently observed in PAH
      patients. Microparticles derived from platelets, inflammatory cells and the
      endothelium are an increasingly well-recognized signal in a variety of
      cardiovascular diseases, including PAH. This review will focus on the roles of
      coagulation, thrombosis, platelet activation and microparticles in the pathology
      and progression of PAH. 

PMID- 24747562
TI  - The rise (and decline?) of biotechnology.
AB  - Since the 1970s, biotechnology has been a key innovator in drug development. An
      analysis of FDA-approved therapeutics demonstrates pharmaceutical companies
      outpace biotechs in terms of new approvals but biotechnology companies are now
      responsible for earlier-stage activities (patents, INDs or clinical development).
      The number of biotechnology organizations that contributed to an FDA approval
      began declining in the 2000s and is at a level not seen since the 1980s. Whereas
      early biotechnology companies had a decade from first approval until acquisition,
      the average acquisition of a biotechnology company now occurs months before their
      first FDA approval. The number of hybrid organizations that arise when
      pharmaceutical companies acquire biotechnology is likewise declining, raising
      questions about the sustainability of biotechnology. 

PMID- 24747563
TI  - Bile acids override steatosis in farnesoid X receptor deficient mice in a model
      of non-alcoholic steatohepatitis.
AB  - Non-alcoholic fatty liver disease (NAFLD) is one of the most common liver
      diseases, and the pathogenesis is still not well known. The farnesoid X receptor
      (FXR) is a member of the nuclear hormone receptor superfamily and plays an
      essential role in maintaining bile acid and lipid homeostasis. In this study, we
      study the role of FXR in the pathogenesis of NFALD. We found that FXR deficient
      (FXR(-/-)) mice fed methionine- and choline-deficient (MCD) diet had higher serum
      ALT and AST activities and lower hepatic triglyceride levels than wild-type (WT)
      mice fed MCD diet. Expression of genes involved in inflammation (VCAM-1) and
      fibrosis (alpha-SMA) was increased in FXR(-/-) mice fed MCD diet (FXR(-/-)/MCD)
      compared to WT mice fed MCD diet (WT/MCD). Although MCD diet significantly
      induced hepatic fibrosis in terms of liver histology, FXR(-/-)/MCD mice showed
      less degree of hepatic steatosis than WT/MCD mice. Moreover, FXR deficiency
      synergistically potentiated the elevation effects of MCD diet on serum and
      hepatic bile acids levels. The super-physiological concentrations of hepatic bile
      acids in FXR(-/-)/MCD mice inhibited the expression of genes involved in fatty
      acid uptake and triglyceride accumulation, which may be an explanation for less
      steatosis in FXR(-/-)/MCD mice in contrast to WT/MCD mice. These results suggest
      that hepatic bile acids accumulation could override simple steatosis in hepatic
      injury during the progression of NAFLD and further emphasize the role of FXR in
      maintaining hepatic bile acid homeostasis in liver disorders and in hepatic
      protection.

PMID- 24747564
TI  - Tetraspanin CD9 modulates human lymphoma cellular proliferation via histone
      deacetylase activity.
AB  - Non-Hodgkin Lymphoma (NHL) is a type of hematological malignancy that affects two
      percent of the overall population in the United States. Tetraspanin CD9 is a cell
      surface protein that has been thoroughly demonstrated to be a molecular
      facilitator of cellular phenotype. CD9 expression varies in two human lymphoma
      cell lines, Raji and BJAB. In this report, we investigated the functional
      relationship between CD9 and cell proliferation regulated by histone deacetylase
      (HDAC) activity in these two cell lines. Introduction of CD9 expression in Raji
      cells resulted in significantly increased cell proliferation and HDAC activity
      compared to Mock transfected Raji cells. The increase in CD9-Raji cell
      proliferation was significantly inhibited by HDAC inhibitor (HDACi) treatment.
      Pretreatment of BJAB cells with HDAC inhibitors resulted in a significant
      decrease in endogenous CD9 mRNA and cell surface expression. BJAB cells also
      displayed decreased cell proliferation after HDACi treatment. These results
      suggest a significant relationship between CD9 expression and cell proliferation
      in human lymphoma cells that may be modulated by HDAC activity. 

PMID- 24747565
TI  - Soni-removal of nucleic acids from inclusion bodies.
AB  - Inclusion bodies (IBs) are commonly formed in Escherichia coli due to over
      expression of recombinant proteins in non-native state. Isolation, denaturation
      and refolding of these IBs is generally performed to obtain functional protein.
      However, during this process IBs tend to form non-specific interactions with
      sheared nucleic acids from the genome, thus getting carried over into downstream
      processes. This may hinder the refolding of IBs into their native state. To
      circumvent this, we demonstrate a methodology termed soni-removal which involves
      disruption of nucleic acid-inclusion body interaction using sonication; followed
      by solvent based separation. As opposed to conventional techniques that use
      enzymes and column-based separations, soni-removal is a cost effective
      alternative for complete elimination of buried and/or strongly bound short
      nucleic acid contaminants from IBs.

PMID- 24747566
TI  - Bortezomib enhances the osteogenic differentiation capacity of human mesenchymal
      stromal cells derived from bone marrow and placental tissues.
AB  - Bortezomib (BZB) is a chemotherapeutic agent approved for treating multiple
      myeloma (MM) patients. In addition, there are several reports showing that
      bortezomib can induce murine mesenchymal stem cells (MSCs) to undergo osteogenic
      differentiation and increase bone formation in vivo. MSCs are the multipotent
      stem cells that have capacity to differentiate into several mesodermal
      derivatives including osteoblasts. Nowadays, MSCs mostly bone marrow derived have
      been considered as a valuable source of cell for tissue replacement therapy. In
      this study, the effect of bortezomib on the osteogenic differentiation of human
      MSCs derived from both bone marrow (BM-MSCs) and postnatal sources such as
      placenta (PL-MSCs) were investigated. The degree of osteogenic differentiation of
      BM-MSCs and PL-MSCs after bortezomib treatment was assessed by alkaline
      phosphatase (ALP) activity, matrix mineralization by Alizarin Red S staining and
      the expression profiles of osteogenic differentiation marker genes, Osterix,
      RUNX2 and BSP. The results showed that 1 nM and 2 nM BZB can induce osteogenic
      differentiation of BM-MSCs and PL-MSCs as demonstrated by increased ALP activity,
      increased matrix mineralization and up-regulation of osteogenic differentiation
      marker genes, Osterix, RUNX2 and BSP as compared to controls. The enhancement of
      osteogenic differentiation of MSCs by bortezomib may lead to the potential
      therapeutic applications in human diseases especially patients with osteopenia.

PMID- 24747567
TI  - Aquaporin 5 increases keratinocyte-derived chemokine expression and NF-kappaB
      activity through ERK activation.
AB  - Aquaporin-5 (AQP5) is a water-selective channel protein that is expressed in
      submucosal glands and alveolar epithelial cells in the lungs. Recent studies have
      revealed that AQPs regulate not only water metabolism, but also some cellular
      functions such as cell growth and migration. Here, we report the role of AQP5 in
      inflammatory responses. In MLE-12 cells, knockdown of AQP5 using siRNA (10-50 nM)
      attenuated TNF-alpha-induced expression of keratinocyte chemoattractant (KC) mRNA
      and protein. Conversely, in NIH-3T3 cells, overexpression of AQP5 increased KC
      expression, NF-kappaB activation, and ERK phosphorylation. The AQP5-induced
      increase of KC expression was diminished by treatment with ERK inhibitors. Taken
      together, we propose a new function of AQP5 as an inflammatory signal
      potentiator, which may be mediated by increased activation of ERK and NF-kappaB.

PMID- 24747568
TI  - A comparison of spatial analysis methods for the construction of topographic maps
      of retinal cell density.
AB  - Topographic maps that illustrate variations in the density of different neuronal
      sub-types across the retina are valuable tools for understanding the adaptive
      significance of retinal specialisations in different species of vertebrates. To
      date, such maps have been created from raw count data that have been subjected to
      only limited analysis (linear interpolation) and, in many cases, have been
      presented as iso-density contour maps with contour lines that have been smoothed
      'by eye'. With the use of stereological approach to count neuronal distribution,
      a more rigorous approach to analysing the count data is warranted and potentially
      provides a more accurate representation of the neuron distribution pattern.
      Moreover, a formal spatial analysis of retinal topography permits a more robust
      comparison of topographic maps within and between species. In this paper, we
      present a new R-script for analysing the topography of retinal neurons and
      compare methods of interpolating and smoothing count data for the construction of
      topographic maps. We compare four methods for spatial analysis of cell count
      data: Akima interpolation, thin plate spline interpolation, thin plate spline
      smoothing and Gaussian kernel smoothing. The use of interpolation 'respects' the
      observed data and simply calculates the intermediate values required to create
      iso-density contour maps. Interpolation preserves more of the data but,
      consequently includes outliers, sampling errors and/or other experimental
      artefacts. In contrast, smoothing the data reduces the 'noise' caused by
      artefacts and permits a clearer representation of the dominant, 'real'
      distribution. This is particularly useful where cell density gradients are
      shallow and small variations in local density may dramatically influence the
      perceived spatial pattern of neuronal topography. The thin plate spline and the
      Gaussian kernel methods both produce similar retinal topography maps but the
      smoothing parameters used may affect the outcome. 

PMID- 24747569
TI  - Label-free picomolar detection of Pb2+ using atypical icosahedra gold
      nanoparticles and rolling circle amplification.
AB  - A novel electrochemical sensing system for Pb(2+) has been developed based on
      atypical icosahedral gold nanoparticle (AI-AuNPs) modification and the improved
      rolling circle amplification (RCA). The newly synthesized AI-AuNPs which were
      applied to modify the gold electrode surface greatly enhanced the sensitivity and
      expanded the detection range due to its large specific surface area and a large
      density of irrational kinks and step atoms on the particle surface. Additionally,
      the improved RCA introduced a manipulated circular template DNA which can be
      hybridized with the primer obtained from the DNAzymes catalysis reaction in the
      presence of Pb(2+) as a cofactor to simplify the RCA procedure, and the largely
      elongated RCA products at the same time efficiently blocked the electron transfer
      at the electrode surface, thus significantly increased the electrochemical
      signal. The design of the label free electrochemical impendence sensing strategy
      was evidenced to be a highly sensitive and selective method for the lead ions
      monitoring compared with the previous reports and the detection range was 1 pM-1
      MUMU with a detection limit of 290 fM (3delta rule). Furthermore, the proposed
      detection system was also environmental-friendly and inexpensive, which can be
      successfully used in real serum sample detection.

PMID- 24747570
TI  - A regeneratable, label-free, localized surface plasmon resonance (LSPR)
      aptasensor for the detection of ochratoxin A.
AB  - Binding of an analyte on the surface of a nanoparticle typically promotes a
      change in the local refractive index, which gives rise to a shift in the
      wavelength of the localized surface plasmon resonance (LSPR) absorption band. The
      magnitude of the LSPR wavelength change is dependent on both the location of the
      analyte relative to the surface of the nanoparticle and the degree of alteration
      of the refractive index. We have employed this phenomenon as the basis for
      designing a new, label-free approach for the detection of the toxic mold
      mycotoxin, ochratoxin A (OTA) that employs a gold nanorod (GNR) and an aptamer
      target binding mechanism. In this system, binding of OTA causes an accumulation
      of OTA and G-quadruplex structure of the aptamer. This process results in a
      longitudinal wavelength shift of the LSPR peak associated with a change in the
      local refractive index near the GNR surface. By using this method, OTA can be
      quantitatively detected at concentrations lower than 1 nM. In addition, the
      results of this effort show that aptamer functionalized GNR substrate is robust
      in that it can be regenerated for reuse over seven times by heating in methanol
      at 70  degrees C to remove OTA. Moreover, the proposed biosensor system exhibits
      high selectivity for OTA over other mycotoxins. Finally, the sensor can be
      employed to detect OTA in ground corn samples with excellent recovery levels.

PMID- 24747571
TI  - Ultrasensitive detection of deltamethrin by immune magnetic nanoparticles
      separation coupled with surface plasmon resonance sensor.
AB  - Small molecules or analytes present in trace level are difficult to be detected
      directly using conventional surface plasmon resonance (SPR) sensor, due to its
      small changes in the refractive index induced by the binding of these analytes on
      the sensor surface. In this paper, a new approach that combines SPR sensor
      technology with Fe3O4 magnetic nanoparticles (MNPs) assays is developed for
      directly detecting of deltamethrin in soybean. The Fe3O4 MNPs conjugated with
      antibodies specific to antigen serves as both labels for enhancing refractive
      index change due to the capture of target analyte, and "vehicles" for the rapid
      delivery of analyte from a sample solution to the sensor surface. Meanwhile, SPR
      direct detection format without Fe3O4 MNPs and gas chromatography (GC) analysis
      were conducted for detection of deltamethrin in soybean to demonstrate the
      amplification effect of Fe3O4 MNPs. A good linear relationship was obtained
      between SPR responses and deltamethrin concentrations over a range of 0.01-1
      ng/mL with the lowest measurable concentration of 0.01 ng/mL. The results reveal
      that the detection sensitivity for deltamethrin was improved by 4 orders of
      magnitude compared with SPR direct detection format. The recovery of 95.5-119.8%
      was obtained in soybean. The excellent selectivity of the present biosensor is
      also confirmed by two kinds of pesticides (fenvalerate and atrazine) as controls.
      This magnetic separation and amplification strategy has great potential for
      detection of other small analytes in trace level concentration, with high
      selectivity and sensitivity by altering the target-analyte-capture agent labeled
      to the carboxyl-coated Fe3O4 MNPs.

PMID- 24747572
TI  - Copper-doped titanium dioxide nanoparticles as dual-functional labels for
      fabrication of electrochemical immunosensors.
AB  - Constructions of versatile electroactive labels are key issues in the development
      of electrochemical immunosensors. In this study, copper-doped titanium dioxide
      nanoparticle (Cu@TiO2) was synthesized and used as labels for fabrication of
      sandwich-type electrochemical immunosensors on glassy carbon electrode (GCE). Due
      to the presence of copper ions, Cu@TiO2 shows a strong response current when
      coupled to an electrode. The prepared nanocomposite also shows high
      electrocatalytic activity towards reduction of hydrogen peroxide (H2O2). The dual
      functionality of Cu@TiO2 enables the fabrication of immunosensor using different
      detection modes, that is, square wave voltammetry (SWV) or chronoamperometry
      (CA). While Cu@TiO2 was used as labels of secondary antibodies (Ab2), carboxyl
      functionalized graphene oxide (CFGO) was used as electrode materials to
      immobilize primary antibodies (Ab1). Using human immunoglobulin G (IgG) as a
      model analyte, the immunosensor shows high sensitivity, acceptable stability and
      good reproducibility for both detection modes. Under optimal conditions, a linear
      range from 0.1 pg/mL to 100 ng/mL with a detection limit of 0.052 pg/mL was
      obtained for SWV analysis. For CA analysis, a wider linear range from 0.01 pg/mL
      to 100 ng/mL and a lower detection limit of 0.0043 pg/mL were obtained. The
      proposed metal ion-based enzyme-free and noble metal-free immunosensor may have
      promising applications in clinical diagnoses and many other fields.

PMID- 24747573
TI  - Automated microfluidically controlled electrochemical biosensor for the rapid and
      highly sensitive detection of Francisella tularensis.
AB  - Tularemia is a highly infectious zoonotic disease caused by a Gram-negative
      coccoid rod bacterium, Francisella tularensis. Tularemia is considered as a life
      threatening potential biological warfare agent due to its high virulence,
      transmission, mortality and simplicity of cultivation. In the work reported here,
      different electrochemical immunosensor formats for the detection of whole F.
      tularensis bacteria were developed and their performance compared. An anti
      Francisella antibody (FB11) was used for the detection that recognises the
      lipopolysaccharide found in the outer membrane of the bacteria. In the first
      approach, gold-supported self-assembled monolayers of a carboxyl terminated
      bipodal alkanethiol were used to covalently cross-link with the FB11 antibody. In
      an alternative second approach F(ab) fragments of the FB11 antibody were
      generated and directly chemisorbed onto the gold electrode surface. The second
      approach resulted in an increased capture efficiency and higher sensitivity.
      Detection limits of 4.5 ng/mL for the lipopolysaccharide antigen and 31
      bacteria/mL for the F. tularensis bacteria were achieved. Having demonstrated the
      functionality of the immunosensor, an electrode array was functionalised with the
      antibody fragment and integrated with microfluidics and housed in a tester set-up
      that facilitated complete automation of the assay. The only end-user intervention
      is sample addition, requiring less than one-minute hands-on time. The use of the
      automated microfluidic set-up not only required much lower reagent volumes but
      also the required incubation time was considerably reduced and a notable increase
      of 3-fold in assay sensitivity was achieved with a total assay time from sample
      addition to read-out of less than 20 min.

PMID- 24747574
TI  - Executive control processes underlying multi-item working memory.
AB  - A dominant view of prefrontal cortex (PFC) function is that it stores task
      relevant information in working memory. To examine this and determine how it
      applies when multiple pieces of information must be stored, we trained two
      subjects to perform a multi-item color change detection task and recorded
      activity of neurons in PFC. Few neurons encoded the color of the items. Instead,
      the predominant encoding was spatial: a static signal reflecting the item's
      position and a dynamic signal reflecting the subject's covert attention. These
      findings challenge the notion that PFC stores task-relevant information. Instead,
      we suggest that the contribution of PFC is in controlling the allocation of
      resources to support working memory. In support of this, we found that increased
      power in the alpha and theta bands of PFC local field potentials, which are
      thought to reflect long-range communication with other brain areas, was
      correlated with more precise color representations. 

PMID- 24747575
TI  - Scaling down of balanced excitation and inhibition by active behavioral states in
      auditory cortex.
AB  - Cortical sensory processing is modulated by behavioral and cognitive states. How
      this modulation is achieved by changing synaptic circuits remains largely
      unknown. In awake mouse auditory cortex, we found that sensory-evoked spike
      responses of layer 2/3 (L2/3) excitatory cells were scaled down with preserved
      sensory tuning when mice transitioned from quiescence to active behaviors,
      including locomotion, whereas L4 and thalamic responses were unchanged. Whole
      cell voltage-clamp recordings revealed that tone-evoked synaptic excitation and
      inhibition exhibited a robust functional balance. The change to active states
      caused scaling down of excitation and inhibition at approximately equal levels in
      L2/3 cells, but resulted in no synaptic changes in L4 cells. This lamina-specific
      gain control could be attributed to an enhancement of L1-mediated inhibitory
      tone, with L2/3 parvalbumin inhibitory neurons also being suppressed. Thus, L2/3
      circuits can adjust the salience of output in accordance with momentary
      behavioral demands while maintaining the sensitivity and quality of sensory
      processing. 

PMID- 24747576
TI  - The age and genomic integrity of neurons after cortical stroke in humans.
AB  - It has been unclear whether ischemic stroke induces neurogenesis or neuronal DNA
      rearrangements in the human neocortex. Using immunohistochemistry; transcriptome,
      genome and ploidy analyses; and determination of nuclear bomb test-derived (14)C
      concentration in neuronal DNA, we found neither to be the case. A large
      proportion of cortical neurons displayed DNA fragmentation and DNA repair a short
      time after stroke, whereas neurons at chronic stages after stroke showed DNA
      integrity, demonstrating the relevance of an intact genome for survival. 

PMID- 24747578
TI  - Quantitative insights for the design of substrate-based SIRT1 inhibitors.
AB  - Sirtuin 1 (SIRT1) is the most studied human sirtuin and it catalyzes the
      deacetylation reaction of acetylated lysine residues of its target proteins, for
      example histones. It is a promising drug target in the treatment of age-related
      diseases, such as neurodegenerative diseases and cancer. In this study, a series
      of known substrate-based sirtuin inhibitors was analyzed with comparative
      molecular field analysis (CoMFA), which is a three-dimensional quantitative
      structure-activity relationships (3D-QSAR) technique. The CoMFA model was
      validated both internally and externally, producing the statistical values
      concordance correlation coefficient (CCC) of 0.88, the mean value r(2)m of 0.66
      and Q(2)F3 of 0.89. Based on the CoMFA interaction contours, 13 new potential
      inhibitors with high predicted activity were designed, and the activities were
      verified by in vitro measurements. This work proposes an effective approach for
      the design and activity prediction of new potential substrate-based SIRT1
      inhibitors. 

PMID- 24747577
TI  - Population code in mouse V1 facilitates readout of natural scenes through
      increased sparseness.
AB  - Neural codes are believed to have adapted to the statistical properties of the
      natural environment. However, the principles that govern the organization of
      ensemble activity in the visual cortex during natural visual input are unknown.
      We recorded populations of up to 500 neurons in the mouse primary visual cortex
      and characterized the structure of their activity, comparing responses to natural
      movies with those to control stimuli. We found that higher order correlations in
      natural scenes induced a sparser code, in which information is encoded by
      reliable activation of a smaller set of neurons and can be read out more easily.
      This computationally advantageous encoding for natural scenes was state-dependent
      and apparent only in anesthetized and active awake animals, but not during quiet
      wakefulness. Our results argue for a functional benefit of sparsification that
      could be a general principle governing the structure of the population activity
      throughout cortical microcircuits. 

PMID- 24747579
TI  - Inhibitory effects of p-aminohippurate and probenecid on the renal clearance of
      adefovir and benzylpenicillin as probe drugs for organic anion transporter (OAT)
      1 and OAT3 in humans.
AB  - Probe substrates for, and inhibitors of, specific transporters are desired to
      evaluate quantitatively the in vivo functions of transporters in humans. Based on
      published data, adefovir and benzylpenicillin were selected as organic anion
      transporter (OAT) 1- and OAT3-selective probe substrates, respectively. In human
      kidney slices, probenecid potently inhibited the uptake of both adefovir and
      benzylpenicillin with inhibition constant (Ki) values of 18.6+/-5.1 and 12.6+/
      4.2MUM, respectively, whereas p-aminohippurate (PAH) preferentially inhibited
      adefovir uptake. A clinical drug-interaction study involving healthy subjects was
      performed to investigate the dose-dependent inhibition potencies of probenecid
      and PAH on the renal clearance of the probe substrates. Adefovir or
      benzylpenicillin was coadministered with different oral doses of probenecid (500,
      750, or 1500mg) or intravenous PAH infusion rates (70, 120, or 210mg/min/person)
      to the same subject using a crossover design. The renal clearance of adefovir was
      reduced by 45% and 46% in the subjects treated with the maximum dose of
      probenecid and PAH, respectively, which was in accordance with the results of in
      vitro inhibition study. On the other hand, renal clearance of benzylpenicillin
      was reduced by 78% in the subjects treated with the maximum dose of probenecid
      (1500mg), which could be explained by its in vitro Ki values. However, PAH
      unexpectedly increased the renal clearance of benzylpenicillin by 47%. These
      results suggest that adefovir and benzylpenicillin can be used as probe drugs for
      OAT1 and OAT3, respectively, and that PAH can be used to investigate the role of
      OAT1 in the urinary excretion of drugs in humans, whereas it may modulate other
      transport processes in the kidney. 

PMID- 24747581
TI  - Elevated levels of pro-inflammatory oxylipins in older subjects are normalized by
      flaxseed consumption.
AB  - BACKGROUND AND AIMS: Oxylipins, including eicosanoids, are highly bioactive
      molecules endogenously produced from polyunsaturated fatty acids. Oxylipins play
      a key role in chronic disease progression. It is possible, but unknown, if
      oxylipin concentrations change with the consumption of functional foods or differ
      with subject age. METHODS: Therefore, in a parallel comparator trial, 20 healthy
      individuals were recruited into a younger (19-28years) or older (45-64years) age
      group (n=10/group). Participants ingested one muffin/day containing 30g of milled
      flaxseed (6g alpha-linolenic acid) for 4weeks. Plasma oxylipins were isolated
      through solid phase extraction, analyzed with HPLC-MS/MS targeted lipidomics, and
      quantified with the stable isotope dilution method. RESULTS: At baseline, the
      older group exhibited 13 oxylipins >=2-fold the concentration of the younger
      group. Specifically, pro-inflammatory oxylipins 5-hydroxyeicosatetraenoic acid,
      9,10,13-trihydroxyoctadecenoic acid, and 9,12,13-trihydroxyoctadecenoic acid were
      significantly greater in the older (1.1+/-0.23nM, 5.6+/-0.84nM, and 4.5+/-0.58nM,
      respectively) versus the younger group (0.34+/-0.12nM, 3.5+/-0.33nM, and 3.0+/
      0.24nM, respectively) (p<0.05). After 4weeks of flaxseed consumption the number
      of oxylipins that were >=2-fold higher in the older versus the younger group was
      reduced to 3. 5-Hydroxyeicosatetraenoic acid, 9,10,13-trihydroxyoctadecenoic
      acid, and 9,12,13-trihydroxyoctadecenoic acid decreased in the older group to
      concentrations equivalent to the younger group after flaxseed consumption.
      CONCLUSION: These data suggest a potential role for oxylipins in the aging
      process and how nutritional interventions like flaxseed can beneficially disrupt
      these biological changes associated with inflammation and aging.

PMID- 24747580
TI  - Phase variation and host immunity against high molecular weight (HMW) adhesins
      shape population dynamics of nontypeable Haemophilus influenzae within human
      hosts.
AB  - Nontypeable Haemophilus influenzae (NTHi) is a bacterium that resides within the
      human pharynx. Because NTHi is human-restricted, its long-term survival is
      dependent upon its ability to successfully colonize new hosts. Adherence to host
      epithelium, mediated by bacterial adhesins, is one of the first steps in NTHi
      colonization. NTHi express several adhesins, including the high molecular weight
      (HMW) adhesins that mediate attachment to the respiratory epithelium where they
      interact with the host immune system to elicit a strong humoral response. hmwA,
      which encodes the HMW adhesin, undergoes phase variation mediated by 7-base pair
      tandem repeats located within its promoter region. Repeat number affects both
      hmwA transcription and HMW-adhesin production such that as the number of repeats
      increases, adhesin production decreases. Cells expressing large amounts of HMW
      adhesins may be critical for the establishment and maintenance of NTHi
      colonization, but they might also incur greater fitness costs when faced with an
      adhesin-specific antibody-mediated immune response. We hypothesized that the
      occurrence of large deletion events within the hmwA repeat region allows NTHi
      cells to maintain adherence in the presence of antibody-mediated immunity. To
      study this, we developed a mathematical model, incorporating hmwA phase variation
      and antibody-mediated immunity, to explore the trade-off between bacterial
      adherence and immune evasion. The model predicts that antibody levels and
      avidity, catastrophic loss rates, and population carrying capacity all
      significantly affected numbers of adherent NTHi cells within a host. These
      results suggest that the occurrence of large, yet rare, deletion events allows
      for stable maintenance of a small population of adherent cells in spite of HMW
      adhesin specific antibody-mediated immunity. These adherent subpopulations may be
      important for sustaining colonization and/or maintaining transmission. 

PMID- 24747583
TI  - Thin-layer chromatographic (TLC) separations and bioassays of plant extracts to
      identify antimicrobial compounds.
AB  - A common screen for plant antimicrobial compounds consists of separating plant
      extracts by paper or thin-layer chromatography (PC or TLC), exposing the
      chromatograms to microbial suspensions (e.g. fungi or bacteria in broth or agar),
      allowing time for the microbes to grow in a humid environment, and visualizing
      zones with no microbial growth. The effectiveness of this screening method, known
      as bioautography, depends on both the quality of the chromatographic separation
      and the care taken with microbial culture conditions. This paper describes
      standard protocols for TLC and contact bioautography with a novel application to
      amino acid-fermenting bacteria. The extract is separated on flexible (aluminum
      backed) silica TLC plates, and bands are visualized under ultraviolet (UV) light.
      Zones are cut out and incubated face down onto agar inoculated with the test
      microorganism. Inhibitory bands are visualized by staining the agar plates with
      tetrazolium red. The method is applied to the separation of red clover (Trifolium
      pratense cv. Kenland) phenolic compounds and their screening for activity against
      Clostridium sticklandii, a hyper ammonia-producing bacterium (HAB) that is native
      to the bovine rumen. The TLC methods apply to many types of plant extracts and
      other bacterial species (aerobic or anaerobic), as well as fungi, can be used as
      test organisms if culture conditions are modified to fit the growth requirements
      of the species.

PMID- 24747582
TI  - The effects of age and muscle contraction on AMPK activity and heterotrimer
      composition.
AB  - Sarcopenia is characterized by increased skeletal muscle atrophy due in part to
      alterations in muscle metabolism. AMP-activated protein kinase (AMPK) is a master
      regulator of skeletal muscle metabolic pathways which regulate many cellular
      processes that are disrupted in old-age. Functional AMPK is a heterotrimer
      composed of alpha, beta and gamma subunits, and each subunit can be represented
      in the heterotrimer by one of two (alpha1/alpha2, beta1/beta2) or three
      (gamma1/gamma2/gamma3) isoforms. Altered isoform composition affects AMPK
      localization and function. Previous work has shown that overall AMPK activation
      with endurance-type exercise is blunted in old vs. young skeletal muscle.
      However, details regarding the activation of the specific isoforms of AMPK, as
      well as the heterotrimeric composition of AMPK in old skeletal muscle, are
      unknown. Our purpose here, therefore, was to determine the effect of old-age on
      1) the activation of the alpha1 and alpha2 catalytic subunits of AMPK in skeletal
      muscle by a continuous contraction bout, and 2) the heterotrimeric composition of
      skeletal muscle AMPK. We studied gastrocnemius (GAST) and tibialis anterior (TA)
      muscles from young adult (YA; 8months old) and old (O; 30months old) male
      Fischer344*Brown Norway F1 hybrid rats after an in situ bout of endurance-type
      contractions produced via electrical stimulation of the sciatic nerve (STIM).
      AMPKalpha phosphorylation and AMPKalpha1 and alpha2 activities were unaffected by
      age at rest. However, AMPKalpha phosphorylation and AMPKalpha2 protein content
      and activity were lower in O vs. YA after STIM. Conversely, AMPKalpha1 content
      was greater in O vs. YA muscle, and alpha1 activity increased with STIM in O but
      not YA muscles. AMPKgamma3 overall concentration and its association with
      AMPKalpha1 and alpha2 were lower in O vs. YA GAST. We conclude that activation of
      AMPKalpha1 is enhanced, while activation of alpha2 is suppressed immediately
      after repeated skeletal muscle contractions in O vs. YA skeletal muscle. These
      changes are associated with changes in the AMPK heterotrimer composition. Given
      the known roles of AMPK alpha1, alpha2 and gamma3, this may contribute to
      sarcopenia and associated muscle metabolic dysfunction. 

PMID- 24747584
TI  - Use of different cell lines for in vitro cultures of bovine respiratory syncytial
      virus.
AB  - This study compared the use of different cell lines for in vitro cultures of
      bovine respiratory syncytial virus (BRSV). The BRSV 375 strain and 3 nasal swabs
      obtained from Simmental calves were used for this study. The culture was
      performed on 3 cell lines: bovine kidney cells (LLC-PK1), bovine tracheal cells
      (TBTR) and primary chicken embryo-related cells (CER). A comparative analysis of
      titres was performed using a microplate agglutination test with human group O
      erythrocytes and bovine erythrocytes. The presence of BRSV in all cell lines was
      confirmed using the reverse transcriptase polymerase chain reaction (RT-PCR)
      method. The first small refractile changes in the LLC-PK1 cells occurred at 48h
      after infection. Syncytial changes were noted 4 days after incubation. Large
      refractile cell changes were observed on day 3 of growth in the TBTR culture.
      Syncytia were observed on the second day after infection in subsequent passages.
      The cytopathic effect in the CER cells occurred 24h after infection, and syncytia
      appeared after 3 passages. Changes in syncytia indicate an adaptation of the
      virus for the infection of cells other than tracheal cells in primary and
      secondary cultures. The highest viral titre was obtained using the TBTR line. The
      titres obtained in the LLC-PK1 and CER cultures averaged 10(1.86)/ml. The low
      virus titres in all culture types suggest the need for research aimed at the
      optimisation of culture conditions. 

PMID- 24747585
TI  - A simple heat dissociation method increases significantly the ELISA detection
      sensitivity of the nonstructural-1 glycoprotein in patients infected with DENV
      type-4.
AB  - The secreted form of the dengue virus (DENV) nonstructural-1 (NS1) glycoprotein
      has been shown to be useful for the diagnosis of DENV infections in patients'
      serum samples. In a number of studies, the sensitivity of the commercially
      available DENV NS1 glycoprotein detection assays was higher against some DENV
      serotypes (DENV-1>DENV-3>DENV-2=DENV-4) than others and were also lower using
      patients' serum samples with secondary versus primary DENV infections. In this
      study, 471 DENV-4 positive acute phase patients' serum samples were selected from
      a large panel collected in Brazil from March 2011 to October 2012 by RT-PCR
      and/or virus isolation followed by serotype determination. The sera from primary
      (n=228) and secondary (n=238) DENV-4 infections were identified using IgM and IgG
      capture ELISAs. The sensitivity of a commercial DENV NS1 glycoprotein detection
      ELISA was then assessed when these serum samples were not pre-treated or pre
      treated by acid or heat dissociation prior to being tested. Acid and heat
      dissociation of patients' serum samples with primary and secondary DENV-4
      infections increased significantly the sensitivity of the DENV NS1 glycoprotein
      detection ELISA from 54.4% to 77.2% (p<0.05) and 82% (p<0.05) and from 39.1% to
      63.9% (p<0.05) and 73.1% (p<0.05), respectively. Treatment of DENV infected
      patients' serum samples using simple and rapid heat dissociation step (100
      degrees C for 5min) was, therefore, shown to be very useful for increasing the
      sensitivity of the DENV NS1 glycoprotein detection ELISA using serum samples from
      either primary or secondary DENV infected patients. 

PMID- 24747586
TI  - Evaluation of an anion exchange resin-based method for concentration of F-RNA
      coliphages (enteric virus indicators) from water samples.
AB  - Enteric viral contaminants in water represent a public health concern, thus
      methods for detecting these viruses or their indicator microorganisms are needed.
      Because enteric viruses and their viral indicators are often found at low
      concentrations in water, their detection requires upfront concentration methods.
      In this study, a strong basic anion exchange resin was evaluated as an adsorbent
      material for the concentration of F-RNA coliphages (MS2, Qbeta, GA, and HB-P22).
      These coliphages are recognized as enteric virus surrogates and fecal indicator
      organisms. Following adsorption of the coliphages from 50ml water samples, direct
      RNA isolation and real time RT-PCR detection were performed. In water samples
      containing 10(5)pfu/ml of the F-RNA coliphages, the anion exchange resin (IRA
      900) adsorbed over 96.7% of the coliphages present, improving real time RT-PCR
      detection by 5-7 cycles compared to direct testing. F-RNA coliphage RNA recovery
      using the integrated method ranged from 12.6% to 77.1%. Resin-based concentration
      of samples with low levels of the F-RNA coliphages allowed for 10(0)pfu/ml (MS2
      and Qbeta) and 10(-1)pfu/ml (GA and HB-P22) to be detected. The resin-based
      method offers considerable advantages in cost, speed, simplicity and field
      adaptability. 

PMID- 24747587
TI  - Development of a Luminex assay for the simultaneous detection of human enteric
      viruses in sewage and river water.
AB  - Real time PCR (qPCR) is increasingly being used for viral detection in aquatic
      environments because it enables high specificity and sensitivity of detection.
      However, the limited number of fluorescent reporter dyes restricts its multiplex
      application. In this study, a multiplex Luminex assay was established for the
      simultaneous detection of human adenovirus (HAdV), human polyomavirus (HPyV),
      enterovirus (EV), rotavirus (RoV), norovirus GI (NoVGI) and norovirus GII
      (NoVGII). Different river water and wastewater samples were tested for the
      viruses using both qPCR and the multiplex Luminex xMAP assay. HAdV and HPyV were
      the most abundant in all environmental samples. HAdV was detected in all river
      water and wastewater samples, and HPyV was detected in 79% of river water and
      95.8% of wastewater samples. The multiplex xMAP assay revealed high specificity
      and no cross-reactivity. Using the multiplex Luminex assay, the viral detection
      rates in river water samples were lower than the rates obtained by qPCR for all
      viruses. Conversely, in wastewater samples, the viral detection rates were the
      same for both methods. In addition, the analytical sensitivity of the monoplex
      Luminex assay was comparable to or lower than qPCR. Results suggest that the
      multiplex Luminex assay could be a reliable method for the simultaneous detection
      of viral pathogens in wastewater. 

PMID- 24747588
TI  - Four DNA extraction methods used in loop-mediated isothermal amplification for
      rapid adenovirus detection.
AB  - Loop-mediated isothermal amplification (LAMP) assays have become powerful tools
      for rapid diagnosis of infectious diseases. A more efficient, convenient and
      cheaper method for template preparation from the pellets or supernatants of
      nasopharyngeal aspirates was sought. Three DNA extraction methods (boiling,
      boiling in 1% Triton X-100, and treating with 0.02M NaOH) were compared with the
      commonly used DNAzol DNA extraction method. DNA preparations were then subjected
      to adenovirus (ADV) detection using LAMP assays and 119 clinical samples. The
      specificities for all three methods were 100% compared with the DNAzol method.
      The sensitivity of the boiling method was greater than that for the other two
      methods. The templates extracted from supernatants of nasopharyngeal aspirates
      using the boiling technique were further evaluated. Higher sensitivity (90.9%)
      and specificity (96.5%) were observed for LAMP assays compared with those from
      quantitative PCR assays. In conclusion, for template preparation, boiling
      supernatants of nasopharyngeal aspirates had comparable sensitivity and
      specificity with the DNAzol method. There were the added advantages that the
      boiling technique was simpler, cheaper, and had a shorter processing time. The
      boiling technique could become a suitable substitute for the DNAzol method when
      LAMP assays are used for ADV detection. 

PMID- 24747589
TI  - Clinical performance evaluation of the BD Veritor System Flu A+B assay.
AB  - Early identification of influenza is important for optimal patient management and
      infection control. Rapid influenza antigen tests have been used routinely in
      clinical settings to confirm clinical suspicion, despite their low sensitivity.
      To improve sensitivity, various influenza point-of-care test reader systems have
      been developed. This study evaluated the clinical performance of a digital
      readout rapid influenza diagnostic test (RIDT), the BD VeritorTM System Flu A+B
      assay (BD). Nasopharyngeal swabs taken from 250 patients (influenza A positive,
      n=75; influenza B positive, n=75; and influenza negative, n=100) were analyzed
      using the BinaxNOW(r) Influenza A/B antigen kit (BN), SD Influenza Ag A/B kit
      (SD), BD, real-time reverse transcriptase polymerase chain reaction (RT-PCR), and
      an influenza virus culture. Compared to RT-PCR, the sensitivities of BN, SD, and
      BD were 56.0, 53.3, and 72.0%, respectively, for influenza A and 57.3, 65.3, and
      69.3%, respectively, for influenza B. No false-positive results were noted with
      the three rapid antigen tests. For influenza A, the average RT-PCR threshold
      cycle (Ct) for specimens that tested positive using BD was higher than that for
      specimens that tested positive using BN and SD. BD is a sensitive and easy method
      for the early detection of influenza A and B.

PMID- 24747590
TI  - Stability of infectious human coronavirus NL63.
AB  - The human coronavirus NL63 was identified in 2004 and subsequent studies showed
      its worldwide distribution. Infection with this pathogen is associated with upper
      and lower respiratory tract diseases of mild to moderate severity. Furthermore,
      HCoV-NL63 is the main cause of croup in children. Within this study an optimal
      protocol for freeze-drying that allows safe and effective preservation of HCoV
      NL63 infectious material was developed. Lyophilized virus preparations can be
      stored either at ambient temperature or at +4 degrees C. In the latter case
      samples may be stored for at least two months. Surprisingly, conducted analysis
      showed that HCoV-NL63 virions are exquisitely stable in liquid media and can be
      stored also without preservatives at ambient temperature for up to 14 days.

PMID- 24747591
TI  - Combined elevation of microRNA-196a and microRNA-196b in sera predicts
      unfavorable prognosis in patients with osteosarcomas.
AB  - AIM: To investigate whether the aberrant expression of microRNA (miR)-196a and
      miR-196b can be used as potential prognostic markers of human osteosarcoma.
      METHODS: Quantitative real-time reverse transcriptase-polymerase chain reaction
      (qRT-PCR) analysis was performed to detect the expression levels of miR-196a and
      miR-196b in osteosarcoma tissues and patients' sera. RESULTS: Expression levels
      of miR-196a and miR-196b in osteosarcoma tissues were both significantly higher
      than those in noncancerous bone tissues (both p<0.001), in line with which, the
      serum levels of the two miRNAs were also markedly upregulated in patients with
      osteosarcomas compared with healthy controls (both p<0.001). Then, the elevation
      of serum miR-196a and miR-196b levels both more frequently occurred in
      osteosarcoma patients with high tumor grade (p=0.008 and 0.01, respectively),
      positive metastasis (p=0.001 and 0.006, respectively) and recurrence (p=0.001 and
      0.006, respectively). Moreover, high serum miR-196a, high serum miR-196b and
      conjoined expression of miR-196a/miR-196b were all independent prognostic factors
      for OS (overall survival) and DFS (disease-free survival) of osteosarcoma
      patients. CONCLUSION: Our present data indicate the involvement of miR-196a and
      miR-196b upregulation in the pathogenesis of osteosarcoma. More importantly, the
      altered levels of circulating miR-196a and miR-196b might have great potential to
      serve as novel and non-invasive prognostic factors for this malignancy.

PMID- 24747592
TI  - Expression of aldo-keto reductase family 1 member b10 in the early stages of
      human hepatocarcinogenesis.
AB  - Aldo-keto reductase family 1, member B10 (AKR1B10), a cancer-related
      oxidoreductase, is expressed in well-differentiated hepatocellular carcinomas
      (HCCs). However, AKR1B10 levels are minimal in normal liver tissues (NLs),
      similar to the 70-kilodalton heat shock protein (HSP70) and glypican-3. Moreover,
      the role of AKR1B10 in chronic hepatitis or cirrhosis, which are considered
      preneoplastic conditions for HCC, has not been fully elucidated. The aim of this
      study was to evaluate the expression of AKR1B10, HSP70, and glypican-3 in 61 HCC
      tissue samples compared to corresponding non-tumorous liver tissues (NTs),
      comprising 42 chronic hepatitis and 19 cirrhosis cases to clarify the
      significance of molecular changes at the preneoplastic stages of HCC.
      Immunohistochemical analysis demonstrated that the median expression levels of
      AKR1B10 were higher in HCCs than in NTs (p<0.001) and higher in NTs than NLs
      (p<0.001) with 54.8%, 2.1%, and 0.3% expression in HCCs, NTs, and NLs,
      respectively. HSP70 and glypican-3 were expressed in HCCs, but minimally in NTs
      and NLs with no significant difference between expression in NTs and NLs.
      Furthermore, a multivariate analysis identified an association between hepatic
      steatosis and AKR1B10 expression in NTs (p=0.020). Of the three protein expressed
      in well-differentiated HCCs, only AKR1B10 was upregulated in preneoplastic
      conditions, and a steatosis-related factor might influence its expression.

PMID- 24747593
TI  - Vitamin D: link between osteoporosis, obesity, and diabetes?
AB  - Vitamin D (1,25(OH)2D3) is a steroid hormone that has a range of physiological
      functions in skeletal and nonskeletal tissues, and can contribute to prevent
      and/or treat osteoporosis, obesity, and Type 2 diabetes mellitus (T2DM). In bone
      metabolism, vitamin D increases the plasma levels of calcium and phosphorus,
      regulates osteoblast and osteoclast the activity, and combats PTH hypersecretion,
      promoting bone formation and preventing/treating osteoporosis. This evidence is
      supported by most clinical studies, especially those that have included calcium
      and assessed the effects of vitamin D doses (>=800 IU/day) on bone mineral
      density. However, annual megadoses should be avoided as they impair bone health.
      Recent findings suggest that low serum vitamin D is the consequence (not the
      cause) of obesity and the results from randomized double-blind clinical trials
      are still scarce and inconclusive to establish the relationship between vitamin
      D, obesity, and T2DM. Nevertheless, there is evidence that vitamin D inhibits fat
      accumulation, increases insulin synthesis and preserves pancreatic islet cells,
      decreases insulin resistance and reduces hunger, favoring obesity and T2DM
      control. To date, there is not enough scientific evidence to support the use of
      vitamin D as a pathway to prevent and/or treat obesity and T2DM. 

PMID- 24747594
TI  - A20 overexpression inhibits lipopolysaccharide-induced NF-kappaB activation,
      TRAF6 and CD40 expression in rat peritoneal mesothelial cells.
AB  - Zinc finger protein A20 is a key negative regulator of inflammation. However,
      whether A20 may affect inflammation during peritoneal dialysis (PD)-associated
      peritonitis is still unclear. This study was aimed to investigate the effect of
      A20 overexpression on lipopolysaccharide (LPS)-induced inflammatory response in
      rat peritoneal mesothelial cells (RPMCs). Isolated and cultured RPMCs in vitro.
      Plasmid pGEM-T easy-A20 was transfected into RPMCs by LipofectamineTM2000. The
      protein expression of A20, phospho-IkappaBalpha, IkappaBalpha, TNF receptor
      associated factor (TRAF) 6 and CD40 were analyzed by Western blot. The mRNA
      expression of TRAF6, CD40, interleukin-6 (IL-6) and tumor necrosis factor-alpha
      (TNF-alpha) were determined by real time-PCR. NF-kappaB p65 DNA binding activity,
      IL-6 and TNF-alpha levels in cells culture supernatant were determined by ELISA.
      Our results revealed that RPMCs overexpression of A20 lead to significant
      decrease of LPS-induced IkappaBalpha phosphorylation and NF-kappaB DNA binding
      activity (all p<0.01). In addition, A20 also attenuated the expression of TRAF6,
      CD40, IL-6 and TNF-alpha as well as levels of IL-6 and TNF-alpha in cells culture
      supernatant (all p<0.05). However, A20 only partly inhibited CD40 expression. Our
      study indicated that A20 overexpression may depress the inflammatory response
      induced by LPS in cultured RPMCs through negatively regulated the relevant
      function of adaptors in LPS signaling pathway.

PMID- 24747595
TI  - Radiation-induced changes in serum lipidome of head and neck cancer patients.
AB  - Cancer radiotherapy (RT) induces response of the whole patient's body that could
      be detected at the blood level. We aimed to identify changes induced in serum
      lipidome during RT and characterize their association with doses and volumes of
      irradiated tissue. Sixty-six patients treated with conformal RT because of head
      and neck cancer were enrolled in the study. Blood samples were collected before,
      during and about one month after the end of RT. Lipid extracts were analyzed
      using MALDI-oa-ToF mass spectrometry in positive ionization mode. The major
      changes were observed when pre-treatment and within-treatment samples were
      compared. Levels of several identified phosphatidylcholines, including (PC34),
      (PC36) and (PC38) variants, and lysophosphatidylcholines, including (LPC16) and
      (LPC18) variants, were first significantly decreased and then increased in post
      treatment samples. Intensities of changes were correlated with doses of radiation
      received by patients. Of note, such correlations were more frequent when low-to
      medium doses of radiation delivered during conformal RT to large volumes of
      normal tissues were analyzed. Additionally, some radiation-induced changes in
      serum lipidome were associated with toxicity of the treatment. Obtained results
      indicated the involvement of choline-related signaling and potential biological
      importance of exposure to clinically low/medium doses of radiation in patient's
      body response to radiation. 

PMID- 24747596
TI  - Melatonin prevents chemical-induced haemopoietic cell death.
AB  - Melatonin (MEL), a methoxyindole synthesized by the pineal gland, is a powerful
      antioxidant in tissues as well as within cells, with a fundamental role in
      ameliorating homeostasis in a number of specific pathologies. It acts both as a
      direct radical scavenger and by stimulating production/activity of intracellular
      antioxidant enzymes. In this work, some chemical triggers, with different
      mechanisms of action, have been chosen to induce cell death in U937 hematopoietic
      cell line. Cells were pre-treated with 100 uM MEL and then exposed to hydrogen
      peroxide or staurosporine. Morphological analyses, TUNEL reaction and Orange/PI
      double staining have been used to recognize ultrastructural apoptotic patterns
      and to evaluate DNA behavior. Chemical damage and potential MEL anti-apoptotic
      effects were quantified by means of Tali(r) Image-Based Cytometer, able to
      monitor cell viability and apoptotic events. After trigger exposure, chromatin
      condensation, micronuclei formation and DNA fragmentation have been observed, all
      suggesting apoptotic cell death. These events underwent a statistically
      significant decrease in samples pre-treated with MEL. After caspase inhibition
      and subsequent assessment of cell viability, we demonstrated that apoptosis
      occurs, at least in part, through the mitochondrial pathway and that MEL
      interacts at this level to rescue U937 cells from death. 

PMID- 24747597
TI  - Relaxation of rat aorta by farrerol correlates with potency to reduce
      intracellular calcium of VSMCs.
AB  - Farrerol, isolated from Rhododendron dauricum L., has been proven to be an
      important multifunctional physiologically active component, but its vasoactive
      mechanism is not clear. The present study was performed to observe the vasoactive
      effects of farrerol on rat aorta and to investigate the possible underlying
      mechanisms. Isolated aortic rings of rat were mounted in an organ bath system and
      the myogenic effects stimulated by farrerol were studied. Intracellular Ca2+
      ([Ca2+]in) was measured by molecular probe fluo-4-AM and the activities of L-type
      voltage-gated Ca2+ channels (LVGC) were studied with whole-cell patch clamp in
      cultured vascular smooth muscle cells (VSMCs). The results showed that farrerol
      significantly induced dose-dependent relaxation on aortic rings, while this
      vasorelaxation was not affected by NG-nitro-l-arginine methylester ester or
      endothelium denudation. In endothelium-denuded aortas, farrerol also reduced Ca2+
      induced contraction on the basis of the stable contraction induced by KCl or
      phenylephrine (PE) in Ca2+-free solution. Moreover, after incubation with
      verapamil, farrerol can induce relaxation in endothelium-denuded aortas
      precontracted by PE, and this effect can be enhanced by ruthenium red, but not by
      heparin. With laser scanning confocal microscopy method, the farrerol-induced
      decline of [Ca2+]in in cultured VSMCs was observed. Furthermore, we found that
      farrerol could suppress Ca2+ influx via LVGC by patch clamp technology. These
      findings suggested that farrerol can regulate the vascular tension and could be
      developed as a practicable vasorelaxation drug. 

PMID- 24747599
TI  - A murine model of myocardial ischemia-reperfusion injury through ligation of the
      left anterior descending artery.
AB  - Acute or chronic myocardial infarction (MI) are cardiovascular events resulting
      in high morbidity and mortality. Establishing the pathological mechanisms at work
      during MI and developing effective therapeutic approaches requires methodology to
      reproducibly simulate the clinical incidence and reflect the pathophysiological
      changes associated with MI. Here, we describe a surgical method to induce MI in
      mouse models that can be used for short-term ischemia-reperfusion (I/R) injury as
      well as permanent ligation. The major advantage of this method is to facilitate
      location of the left anterior descending artery (LAD) to allow for accurate
      ligation of this artery to induce ischemia in the left ventricle of the mouse
      heart. Accurate positioning of the ligature on the LAD increases reproducibility
      of infarct size and thus produces more reliable results. Greater precision in
      placement of the ligature will improve the standard surgical approaches to
      simulate MI in mice, thus reducing the number of experimental animals necessary
      for statistically relevant studies and improving our understanding of the
      mechanisms producing cardiac dysfunction following MI. This mouse model of MI is
      also useful for the preclinical testing of treatments targeting myocardial damage
      following MI. 

PMID- 24747598
TI  - The role of survivin in podocyte injury induced by puromycin aminonucleoside.
AB  - OBJECTIVE: Survivin is a member of the inhibitor of apoptosis protein family,
      which uniquely promotes mitosis and regulates apoptosis in cancer cells. Recent
      studies have demonstrated that survivin also expresses in several normal adult
      cells. In the present study, we aimed to investigate the function of survivin in
      the terminally differentiated epithelial cells, podocytes. METHODS: Survivin
      expression and location were detected by Quantitative Real-Time PCR, western blot
      and fluorescence confocal microscopy methods in normal and injured mouse
      podocytes. Cyto-protection function of survivin was also studied in cultured
      podocyte injured by puromycin aminonucleoside (PAN), transfected with survivin
      siRNA to down-regulate survivin expression, or with survivin plasmid to
      transiently over-express survivin. RESULTS: In podocytes, PAN stimulated
      expressions of survivin and the apoptosis related molecule caspase 3. Knockdown
      of survivin expression by siRNA increased the activation of caspase 3, induced
      podocyte apoptosis and remarkable rearrangement of actin cytoskeleton. Moreover,
      over-expression of survivin inhibited PAN-induced podocyte apoptosis and
      cytoskeleton rearrangement. CONCLUSION: Our data provides the evidence that
      survivin plays an important role in protecting podocytes from apoptosis induced
      by PAN. The mechanism of survivin related anti-apoptosis may, at least partially,
      be through the activation of caspase 3.

PMID- 24747600
TI  - Elongation of mouse prion protein amyloid-like fibrils: effect of temperature and
      denaturant concentration.
AB  - Prion protein is known to have the ability to adopt a pathogenic conformation,
      which seems to be the basis for protein-only infectivity. The infectivity is
      based on self-replication of this pathogenic prion structure. One of possible
      mechanisms for such replication is the elongation of amyloid-like fibrils. We
      measured elongation kinetics and thermodynamics of mouse prion amyloid-like
      fibrils at different guanidine hydrochloride (GuHCl) concentrations. Our data
      show that both increases in temperature and GuHCl concentration help unfold
      monomeric protein and thus accelerate elongation. Once the monomers are unfolded,
      further increases in temperature raise the rate of elongation, whereas the
      addition of GuHCl decreases it. We demonstrated a possible way to determine
      different activation energies of amyloid-like fibril elongation by using folded
      and unfolded protein molecules. This approach separates thermodynamic data for
      fibril-assisted monomer unfolding and for refolding and formation of amyloid-like
      structure. 

PMID- 24747601
TI  - A proton beam therapy system dedicated to spot-scanning increases accuracy with
      moving tumors by real-time imaging and gating and reduces equipment size.
AB  - PURPOSE: A proton beam therapy (PBT) system has been designed which dedicates to
      spot-scanning and has a gating function employing the fluoroscopy-based real-time
      imaging of internal fiducial markers near tumors. The dose distribution and
      treatment time of the newly designed real-time-image gated, spot-scanning proton
      beam therapy (RGPT) were compared with free-breathing spot-scanning proton beam
      therapy (FBPT) in a simulation. MATERIALS AND METHODS: In-house simulation tools
      and treatment planning system VQA (Hitachi, Ltd., Japan) were used for estimating
      the dose distribution and treatment time. Simulations were performed for 48
      motion parameters (including 8 respiratory patterns and 6 initial breathing
      timings) on CT data from two patients, A and B, with hepatocellular carcinoma and
      with clinical target volumes 14.6 cc and 63.1 cc. The respiratory patterns were
      derived from the actual trajectory of internal fiducial markers taken in X-ray
      real-time tumor-tracking radiotherapy (RTRT). RESULTS: With FBPT, 9/48 motion
      parameters achieved the criteria of successful delivery for patient A and 0/48
      for B. With RGPT 48/48 and 42/48 achieved the criteria. Compared with FBPT, the
      mean liver dose was smaller with RGPT with statistical significance (p<0.001); it
      decreased from 27% to 13% and 28% to 23% of the prescribed doses for patients A
      and B, respectively. The relative lengthening of treatment time to administer 3
      Gy (RBE) was estimated to be 1.22 (RGPT/FBPT: 138 s/113 s) and 1.72 (207 s/120 s)
      for patients A and B, respectively. CONCLUSIONS: This simulation study
      demonstrated that the RGPT was able to improve the dose distribution markedly for
      moving tumors without very large treatment time extension. The proton beam
      therapy system dedicated to spot-scanning with a gating function for real-time
      imaging increases accuracy with moving tumors and reduces the physical size, and
      subsequently the cost of the equipment as well as of the building housing the
      equipment.

PMID- 24747602
TI  - MicroRNAs as prognostic markers in ovarian cancer.
AB  - Ovarian cancer (OC) is the most lethal gynecological malignancy among women. Over
      70% of women with OC are diagnosed in advanced stages and most of these cases are
      incurable. Although most patients respond well to primary chemotherapy, tumors
      become resistant to treatment. Mechanisms of chemoresistance in cancer cells may
      be associated with mutational events and/or alterations of gene expression
      through epigenetic events. Although focusing on known genes has already yielded
      new information, previously unknown non-coding RNAs, such as microRNAs (miRNAs),
      also lead insight into the biology of chemoresistance. In this review we
      summarize the current evidence examining the role of miRNAs as biomarkers of
      response and survival to therapy in OC. Beside their clinical implications, we
      also discuss important differences between studies that may have limited their
      use as clinical biomarkers and suggest new approaches. 

PMID- 24747603
TI  - BMAA in shellfish from two Portuguese transitional water bodies suggests the
      marine dinoflagellate Gymnodinium catenatum as a potential BMAA source.
AB  - The neurotoxin beta-N-methylamino-l-alanine (BMAA) and its putative role in
      multiple neurodegenerative diseases have been intensely studied since 2005 when
      the toxin was discovered to be produced by worldwide-distributed cyanobacterial
      species inhabiting terrestrial, marine, brackish, and freshwater ecosystems.
      Recently, BMAA production was also associated with one eukaryotic group, namely,
      diatoms, raising questions about its production by other phytoplanktonic groups.
      To test for BMAA bioavailability in ecosystems where abundant phytoplanktonic
      blooms regularly occur, samples of filter-feeding shellfish were collected in two
      Portuguese transitional water bodies. BMAA content in cockles (Cerastoderma
      edule) collected weekly between September and November 2009 from Ria de Aveiro
      and at least once a month from May to November from Ria Formosa, fluctuated from
      0.079+/-0.055 to 0.354+/-0.066MUg/g DW and from below the limit of detection to
      0.434+/-0.110MUg/g DW, respectively. Simultaneously to BMAA occurrence in
      cockles, paralytic shellfish toxins were detected in shellfish as a result of
      Gymnodinium catenatum blooms indicating a possible link between this marine
      dinoflagellate and BMAA production. Moreover, considerable high BMAA levels,
      0.457+/-0.186MUg/g DW, were then determined in a laboratory grown culture of G.
      catenatum. This work reveals for the first time the presence of BMAA in shellfish
      from Atlantic transitional water bodies and consubstantiate evidences of G.
      catenatum as one of the main sources of BMAA in these ecosystems. 

PMID- 24747604
TI  - Cortical neurogenesis from pluripotent stem cells: complexity emerging from
      simplicity.
AB  - The cerebral cortex contains dozens of neuronal subtypes grouped in specific
      layers and areas. Recent studies have revealed how embryonic and induced
      pluripotent stem cells (PSC) can differentiate into a wide diversity of cortical
      neurons in vitro, while recapitulating many of the temporal and spatial features
      that characterize corticogenesis. PSC-derived neurons can integrate into the
      brain following in vivo transplantation and display patterns of morphology and
      connectivity specific of cortical neurons. PSC-corticogenesis thus emerges as a
      robust model that provides new ways to link cortical development, evolution, and
      disease. 

PMID- 24747605
TI  - Molecular analysis of non structural rotavirus group A enterotoxin gene of bovine
      origin from India.
AB  - The rotavirus enterotoxin NSP4 (nonstructural protein 4), plays a pivotal role in
      viral morphogenesis as well as pathogenesis. In this study, the NSP4 gene of
      rotavirus group A (RVA) isolates of bovine origin isolated in several states of
      India from 2008 to 2011 were characterized. The complete open reading frame of 23
      RVA strains were sequenced and analyzed phylogenetically. Genotype E1 was
      detected for the first time in bovines from India, in addition to the more common
      bovine genotype E2. Sequence similarity analysis of the E1 sequences showed a
      close genetic relatedness to human strains. Six of the bovine E2 genotypes
      strains clustered near bovine and unusual human strains (possible human animal
      reassortant) from Thailand, while the remaining E2 sequences clustered with
      Indian bovine strains. Analysis pointed out one positively selected site (154aa),
      believe to be part of an antigenic region and 123 negatively selected sites.
      Unexpectedly, a pentameric NSP4 structure of the coiled coil domain in the E1
      carrying strains and a monomeric NSP4 in RVA strain P14 (E2) was predicted based
      on homology modeling, potentially affecting the biological properties of NSP4.
      The close relationship between bovine and human rotavirus strains further
      highlights the complex interaction among rotaviruses of different species. 

PMID- 24747606
TI  - Phylogenetic relationships of Leishmania species based on trypanosomatid barcode
      (SSU rDNA) and gGAPDH genes: Taxonomic revision of Leishmania (L.) infantum
      chagasi in South America.
AB  - Phylogenetic studies on trypanosomatid barcode using V7V8 SSU rRNA and gGAPDH
      gene sequences have provided support for redefining some trypanosomatid species
      and positioning new isolates. The genus Leishmania is a slow evolving
      monophyletic group and including important human pathogens. The phylogenetic
      relationships of this genus have been determined by the natural history of its
      vertebrate hosts, vector specificity, clinical manifestations, geographical
      distribution and molecular approaches using different markers. Thus, in an
      attempt to better understand the phylogenetic relationships of Leishmania
      species, we performed phylogenetic analysis on trypanosomatid barcode using V7V8
      SSU rRNA and gGAPDH gene sequences among a large number of Leishmania species and
      also several Brazilian visceral Leishmania infantum chagasi isolates obtained
      from dogs and humans. Our phylogenetic analysis strongly suggested that
      Leishmania hertigi and Leishmania equatoriensis should be taxonomically revised
      so as to include them in the genus Endotrypanum; and supported ancient divergence
      of Leishmania enriettii. This, together with recent data in the literature,
      throws light on the discussion about the evolutionary southern supercontinent
      hypothesis for the origin of Leishmania ssp. and validates L. infantum chagasi
      from Brazil, thus clearly differentiating it from L. infantum, for the first
      time. 

PMID- 24747607
TI  - Stress dependent infection cost of the human malaria agent Plasmodium falciparum
      on its natural vector Anopheles coluzzii.
AB  - Unraveling selective forces that shape vector-parasite interactions has critical
      implications for malaria control. However, it remains unclear whether Plasmodium
      infection induces a fitness cost to their natural mosquito vectors. Moreover,
      environmental conditions are known to affect infection outcome and may impact the
      effect of infection on mosquito fitness. We investigated in the laboratory the
      effects of exposition to and infection by field isolates of Plasmodium falciparum
      on fecundity and survival of a major vector in the field, Anopheles coluzzii
      under different conditions of access to sugar resources after blood feeding. The
      results evidenced fitness costs induced by exposition and infection. When sugar
      was available after blood meal, infected and exposed mosquitoes had either
      reduced or equal to survival to unexposed mosquitoes while fecundity was either
      increased or decreased depending on the blood donor. Under strong nutritional
      stress, survival was reduced for exposed and infected mosquitoes in all assays.
      We therefore provide here evidence of an environmental-dependant reduced survival
      in mosquitoes exposed to infection in a natural and one of the most important
      parasite-mosquito species associations for human malaria transmission. 

PMID- 24747608
TI  - Vibrio cholerae O1 Ogawa El Tor strains with the ctxB7 allele driving cholera
      outbreaks in south-western India in 2012.
AB  - Cholera has been a recurrent epidemic disease in human populations for the past
      200years. We present herein a comparative characterization of clinical Vibrio
      cholerae strains isolated from two consecutive cholera outbreaks in 2012 and
      associated environmental strains from western India. The clinical and toxigenic
      environmental isolates were identified as hybrid V. cholerae O1, serotype Ogawa,
      biotype El Tor carrying the variant ctxB7 allele. Partial sequences of SXT
      integrase from the isolates revealed 100% identity to ICEVchInd5 (Sevagram,
      India, 1994) and VC1786ICE (Haiti, 2013). The full clonal relationship of the
      strains established by RAPD, Box PCR, ERIC PCR and MLST (pyrH, recA and rpoA)
      analyses, and the short time between the two outbreaks, strongly supported that
      both outbreaks were due to a single strain. The study corroborated that faecal
      contamination of the potable water supply was the main reason for the first
      outbreak, which further spread to other areas and resulted in the second
      outbreak. The study concluded that the circulating El Tor variant strains of
      epidemic potential in the region can be a serious concern in the future. 

PMID- 24747609
TI  - MRSA Pediatric clone expressing ermC plus lnuA genes causing nosocomial
      transmission and healthcare workers colonization in a neonatal intensive care
      unit.
AB  - Methicillin-resistant Staphylococcus aureus (MRSA) is a major cause of both
      nosocomial and community-acquired infections. We describe an outbreak caused by
      the MRSA Pediatric clone expressing an unusual lincosamide resistant phenotype.
      Between January and May 2006, an MRSA outbreak was detected at the Neonatal Unit
      of Hospital Interzonal General de Agudos "Evita", Buenos Aires Province,
      Argentina that affected ten patients. Seven isolates from seven patients plus
      five MRSA recovered from health care workers (nasal carriage) were studied. Two
      phenotypes were observed: (i) ELCi (10), resistance to erythromycin and
      lincomycin and inducible resistance to clindamycin; (ii) ELiCi (2), resistance to
      erythromycin and inducible resistance to lincomycin and clindamycin. All 12 MRSA
      were resistant to oxacillin, erythromycin and gentamicin. Isolates expressing the
      ELCi-phenotype showed lincomycin MIC values between 16 and 32mg/L, while the
      remaining 2 isolates with ELiCi-phenotype presented a MIC value of 0.5mg/L. No
      differences were observed between the clindamycin MIC values in both phenotypes,
      ranging 0.25-0.5mg/L. Isolates showing ELCi-phenotype harbored ermC plus lnuA
      genes, and the other two only ermC gene. All 12 isolates were genetically related
      and belonged to the Pediatric clone (ST100) harboring a new variant of SCCmecIV.
      This is the first MRSA outbreak expressing an unusual ELCi phenotype due to a
      combination of ermC plus lnuA genes. 

PMID- 24747610
TI  - GhWRKY40, a multiple stress-responsive cotton WRKY gene, plays an important role
      in the wounding response and enhances susceptibility to ralstonia solanacearum
      infection in transgenic Nicotiana benthamiana.
AB  - WRKY transcription factors form one of the largest transcription factor families
      and function as important components in the complex signaling processes that
      occur during plant stress responses. However, relative to the research progress
      in model plants, far less information is available on the function of WRKY
      proteins in cotton. In the present study, we identified the GhWRKY40 gene in
      cotton (Gossypium hirsutum) and determined that the GhWRKY40 protein is targeted
      to the nucleus and is a stress-inducible transcription factor. The GhWRKY40
      transcript level was increased upon wounding and infection with the bacterial
      pathogen Ralstonia solanacearum. The overexpression of GhWRKY40 down-regulated
      most of the defense-related genes, enhanced the wounding tolerance and increased
      the susceptibility to R. solanacearum. Consistent with a role in multiple stress
      responses, we found that the GhWRKY40 transcript level was increased by the
      stress hormones salicylic acid (SA), methyl jasmonate (MeJA) and ethylene (ET).
      Moreover, GhWRKY40 interacted with the MAPK kinase GhMPK20, as shown using yeast
      two-hybrid and bimolecular fluorescence complementation systems. Collectively,
      these results suggest that GhWRKY40 is regulated by SA, MeJA and ET signaling and
      coordinates responses to wounding and R. solanacearum attack. These findings
      highlight the importance of WRKYs in regulating wounding- and pathogen-induced
      responses. 

PMID- 24747611
TI  - A comparative evaluation of efficacy of chemotherapy, immunotherapy and
      immunochemotherapy in visceral leishmaniasis-an experimental study.
AB  - Visceral leishmaniasis (VL) represents the second most challenging infectious
      disease worldwide, leading to nearly 500,000 new cases and 60,000 deaths
      annually. Ninety per cent of VL cases occur in five countries namely Bangladesh,
      India, Nepal, Sudan and Brazil. No licensed vaccine is available till date
      against any form of leishmaniasis. High toxicity and increasing resistance to the
      current chemotherapeutic regimens have further complicated the situation in VL
      endemic regions of the world. To combat this situation, immunochemotherapy can
      provide a solution. In the present study, an attempt has been made to assess the
      in vivo antileishmanial efficacy of chemotherapy, immunotherapy and
      immunochemotherapy with the use of a first generation antigen Killed Leishmania
      donovani (KLD) along with a standard drug sodium stibogluconate (SSG) and a newly
      tested antileishmanial cisplatin. Inbred BALB/c mice were infected with 10(7)
      promastigotes/0.1 ml of Leishmania donovani. A month after infection, these
      animals were given specific immunotherapy (KLD/KLD+MPL-A) or chemotherapy
      (SSG/cisplatin) or immunochemotherapy (SSG+KLD/SSG+KLD+MPL
      A/cisplatin+KLD/cisplatin+KLD+MPL-A). Animals were sacrificed on 1, 15 and 30(th)
      day post treatment. The efficacy of these combinations was assessed in terms of
      parasite load and by immunological investigations. Infected mice and normal mice
      served as controls. Results showed that combination of drug and KLD significantly
      reduced the parasite burden, enhanced the DTH (Delayed Type Hypersensitivity)
      responses, showed increased levels of IgG2a and decreased levels of IgG1 as
      compared to mice given chemotherapy or immunotherapy alone. Further maximum
      protection was provided by SSG+KLD+MPL-A and it was most effective as depicted by
      98.5% reduction in parasite load, a potent increase in IFN-gamma levels and a
      significant decrease in IL-10 and IL-4 levels thus skewing the immune response
      towards Th1 type. Hence, immunochemotherapy is more effective in control of VL in
      comparison to chemotherapy or immunotherapy.

PMID- 24747612
TI  - PAR2-mediated epigenetic upregulation of alpha-synuclein contributes to the
      pathogenesis of Parkinson's disease.
AB  - Parkinson's disease (PD) is a common neurodegenerative disorder characterized by
      the selective degeneration of projecting dopaminergic neurons in the substantia
      nigra and diminished dopamine levels in the striatum. Accumulating evidences
      demonstrate that the aggregation of extracellular alpha-synuclein contributes to
      the neuroinflammation and neuronal injury in the substantia nigra in the brain of
      patients with PD. Proteinase-activated receptor 2 (PAR2), a G-protein coupled
      receptor, is expressed throughout the peripheral and central nerve system. The
      present study aims to investigate the involvement of PAR2-NF-kappaB signaling in
      the upregulation of alpha-synuclein and motor dysfunction in the rodent model of
      PD. Significantly increased expression of alpha-synuclein was observed in the
      substantia nigra of the rats injected with 1-methyl-4-phenyl-1,2,3,6
      tetrahydropyridine (MPTP). In these rats, significantly increased nigral PAR2 was
      observed, and blockade of PAR2 signaling reduced the alpha-synuclein synthesis in
      substantia nigra and recovered the motor dysfunction in the rats injected with
      MPTP. Furthermore, significantly increased phosphorylation of NF-kappaB subunit
      p65 was detected in these rats, which was abolished by the inhibition of PAR2
      signaling. Blockade of NF-kappaB signaling significantly decreased histone H3
      acetylation in Snca promoter region and alpha-synuclein expression in substantia
      nigra. It also decreased the synthesis of cytokine IL-1beta and TNF-alpha in
      substantia nigra and recovered the motor dysfunction in the rats injected with
      MPTP. These results indicated the critical involvement of PAR2-NF-kappaB
      signaling in the upregulation of alpha-synuclein and motor dysfunction in the
      rodent model of PD, and shed light on the development of novel approaches for the
      treatment of patients with PD. 

PMID- 24747613
TI  - Effects of gypenosides on anxiety disorders in MPTP-lesioned mouse model of
      Parkinson's disease.
AB  - Ethanol extract (GP-EX) of Gynostemma pentaphyllum (GP) ameliorates chronic
      stress-induced anxiety in mice. The present study investigated the effects of
      gypenoside-enriched components (GPS), GP-EX and water extract of GP (GP-WX) on
      MPTP lesion-induced affective disorders in C57BL/6 mice. GPS (50mg/kg) and GP-EX
      (50mg/kg) for 21 day-treatment period improved the symptom of anxiety disorders
      in the MPTP-lesioned mouse model of PD with or without L-DOPA treatment, which
      was examined by the elevated plus-maze and marble burying tests. In these states,
      treatments with GPS (50mg/kg) and GP-EX (50mg/kg) significantly increased the
      brain levels of dopamine and serotonin in the MPTP-lesioned mouse model of PD
      with or without l-DOPA treatment. In addition, treatments with GPS (50mg/kg) and
      GP-EX (50mg/kg) showed protective effects on dopaminergic neurons in MPTP
      lesioned mouse model of PD with or without L-DOPA treatment. In contrast, GPS (30
      mg/kg) and GP-WX (50mg/kg) showed anxiolytic effects in the same animal models,
      but it was not significant. These results suggest that GPS (50mg/kg) and GP-EX
      (50mg/kg) showed anxiolytic effects on affective disorders and protective effects
      on dopaminergic neurons by modulating the brain levels of dopamine and serotonin
      in the MPTP-lesioned mouse model of PD with or without l-DOPA treatment. Clinical
      trials of GPS and GP-EX need to be conducted further so as to develop adjuvant
      therapeutic agents for PD patients.

PMID- 24747614
TI  - Hippocampal place cell responses to distal and proximal cue manipulations in
      dopamine D2 receptor-knockout mice.
AB  - The human hippocampus is critical for learning and memory. In rodents,
      hippocampal pyramidal neurons fire in a location-specific manner and form
      relational representations of environmental cues. The important roles of
      dopaminergic D1 receptors in learning and in hippocampal neural synaptic
      plasticity in novel environments have been previously shown. However, the roles
      of D2 receptors in hippocampal neural plasticity in response to novel and
      familiar spatial stimuli remain unclear. In order to clarify this issue, we
      recorded from hippocampal neurons in dopamine D2 receptor-knockout (D2R-KO) mice
      and their wild-type (WT) littermates during manipulations of distinct spatial
      cues in familiar and novel environments. Here, we report that D2R-KO mice showed
      substantial deficits in place-cell properties (number of place cells, intra-field
      firing rates, spatial tuning, and spatial coherence). Furthermore, although place
      cells in D2R-KO mice responded to manipulations of distal and proximal cues in
      both familiar and novel environments in a manner that was similar to place cells
      in WT mice, place fields were less stable in the D . The axes represent the
      differences between the peak and the valley of each waveform of EL2 and EL3.2R-KO
      mice in the familiar environment, but not in the novel environment. The present
      results suggested that D2 receptors in the hippocampus are important for place
      response stability. The place-cell properties of D2R-KO mice were similar to aged
      animals, suggesting that the alterations of place-cell properties in aged animals
      might be ascribed partly to alterations in the D2R in the HF of aged animals. 

PMID- 24747615
TI  - Effects of systemic administration of sitafloxacin on subgingival microflora and
      antimicrobial susceptibility profile in acute periodontal lesions.
AB  - The aim of this study was to assess the effect(s) of systemic administration of
      sitafloxacin on subgingival microbial profiles of acute periodontal lesions.
      Antimicrobial susceptibility of clinical isolates was also investigated. Patients
      with acute phases of chronic periodontitis were subjected to clinical examination
      and microbiological assessment of their subgingival plaque samples by culture
      technique. Sitafloxacin was then administered (100 mg/day for 5 days)
      systemically. The clinical and microbiological examinations were repeated 6-8
      days after administration. Susceptibilities of clinical isolates to various
      antimicrobials were determined using the broth and agar dilution methods. From
      the sampled sites in 30 participants, a total of 355 clinical isolates (34
      different bacterial species) were isolated and identified. Parvimonas micra,
      Prevotella intermedia and Streptococcus mitis were the most prevalent cultivable
      bacteria in acute sites. Systemic administration of sitafloxacin yielded a
      significant improvement in clinical and microbiological parameters. Among the
      antimicrobials tested, sitafloxacin was the most potent against the clinical
      isolates with an MIC90 of 0.12 MUg/ml at baseline. After administration, most
      clinical isolates were still highly susceptible to sitafloxacin although some
      increase in MICs was observed. The results suggest that systemic administration
      of sitafloxacin is effective against subgingival bacteria isolated from acute
      periodontal lesions. 

PMID- 24747616
TI  - Effect of body mass index on functional recovery after total knee arthroplasty in
      ambulatory overweight or obese women with osteoarthritis.
AB  - OBJECTIVE: The aim of this study was to evaluate the relationship between body
      mass index (BMI) and functional status after total knee arthroplasty (TKA) in
      ambulatory overweight or obese women with knee osteoarthritis (OA). METHODS: The
      study included 78 women who underwent elective primary TKA for osteoarthritis.
      Age, height, body weight and BMI were recorded. Functional status was evaluated
      using the Turkish version of the Knee Injury and Osteoarthritis Outcome Score
      (KOOS). The Timed Up and Go (TUG) test was used to evaluate performance-based
      functional assessment. RESULTS: Mean age of the patients was 66.5 +/- 5.8 (range:
      56 to 79) years and mean duration of symptoms was 9.56 +/- 7.1 years. Body mass
      index was 30 or higher in 47 patients (60%) and between 25 and 29 in 31 (40%).
      Body mass index did not correlate with the KOOS or TUG test. Postoperative KOOS
      scores showed a statistically significant increase (p<0.01). Postoperative TUG
      test values showed significant improvement (p<0.01). CONCLUSION: Body mass index
      had no negative effect on functional recovery and mobility in the ambulatory
      overweight or obese women undergoing TKA. Physical function improved
      significantly after knee arthroplasty.

PMID- 24747617
TI  - Mid-term results of Oxford Phase 3 unicompartmental knee arthroplasty in obese
      patients.
AB  - OBJECTIVE: The aim of this study was to evaluate the mid-term outcomes of Oxford
      Phase 3 unicompartmental knee arthroplasty (UKA) in obese patients in terms of
      prosthesis survival, progression of lateral compartment arthrosis and functional
      outcomes. METHODS: The study included 67 patients, with a body mass index over
      30, treated with mobile bearing Oxford Phase 3 UKA for isolated medial
      osteoarthritis between January 2005 and December 2010. Preoperative and
      postoperative knee range of motion (ROM) and knee scores (Hospital for Special
      Surgery, HSS and Oxford knee scores) were compared. Additionally, prostheses were
      evaluated using Oxford radiographic evaluation criteria at the final follow-up.
      RESULTS: Mean age was 61 years and mean follow-up was 67.5 months. Insert
      dislocation occurred in 3 patients (4.5%). Postoperative knee ROM, HSS and Oxford
      knee scores were significantly improved (p<0.05). There was no sign of prosthesis
      failure or lateral compartment arthrosis in radiographic evaluation at the final
      follow-up. CONCLUSION: Oxford Phase 3 UKA with mobile bearing has good mid-term
      results in obese patients over 60 years of age.

PMID- 24747618
TI  - Comparison of simultaneous bilateral with unilateral total knee arthroplasty.
AB  - OBJECTIVE: The aim of this study was to compare simultaneous bilateral total knee
      arthroplasty (BTKA) and unilateral total knee arthroplasty (UTKA) in terms of
      morbidity, clinical and radiological findings and quality of life. METHODS: The
      study included 48 simultaneous BTKAs (46 females, 2 males; mean age: 64.00 +/-
      8.31 years) and 53 UTKAs (46 females, 7 males; mean age: 64.40 +/- 7.45 years)
      performed between November 2007 and June 2012. Groups were compared with respect
      to comorbidity, complications, blood transfusion, hospital stay, clinical and
      radiological (American Knee Society Score) findings and quality of life (SF-36).
      RESULTS: Three patients in the BTKA group and 1 in the UTKA group required
      intensive care admission due to pulmonary embolism; 2 cases occurred within the
      first postoperative 30 days. One BTKA patient died in the early postoperative
      period and 1 patient from the BTKA and 1 from the UTKA group died within 1 year.
      Hospital stay, perioperative blood transfusion parameters and mortality rates
      were significantly different in favor of UTKA and revision operation rates in
      favor of BTKA (p<0.05). All patients had improved knee and function scores and SF
      36 scores. However, there was no significant difference between the groups
      (p>0.05). CONCLUSION: Simultaneous BTKA should be considered in selected patients
      under 70 years of age with good compliance and no comorbid disease.

PMID- 24747619
TI  - Giant cell tumors of bone: nonsurgical factors associated with local recurrence.
AB  - OBJECTIVE: To determine the rate of giant cell tumor (GCT) recurrence and
      evaluate the factors associated with its recurrence in patients who underwent
      surgery and submitted to only one adjuvant method. METHODS: Forty-one patients
      (22 female, 19 male; mean age: 34.22 +/- 9.70 years) with GCT, who underwent
      surgical and one adjuvant treatment, were evaluated after a mean follow-up period
      of 40.17 +/- 22.08 months. The average tumor size was 8.51 +/- 3.69 cm. The
      tumors in 18 patients (43.9%) were grade II and in 23 patients (56.1%) grade III,
      according to the system developed by Campanacci et al. The surgical margin was
      intralesional resection and curettage in 60.9% of the patients, and marginal or
      wide resection in 39.1%. RESULTS: Nine (22%) of the 41 patients had recurrence.
      None of the gender (p=0.436), age (p=0.310), site of the tumor (p=0.940),
      surgical margins (p=0.400) and the type of the filling material (PMMA or
      autograft) (p=0.680) had an association with recurrence. However, Campanacci
      grade III (p=0.028) and the size of the tumor (p=0.034) was associated with the
      recurrence. CONCLUSION: Tumor size and tumor grade III according to the
      Campanacci system appear to be risk factors for local recurrence after the local
      resection of GCT.

PMID- 24747620
TI  - Red cell distribution width and mortality in patients with hip fracture treated
      with partial prosthesis.
AB  - OBJECTIVE: This study aimed to determine the relationship between red cell
      distribution width (RDW) and mortality in patients that received a partial hip
      prosthesis. METHODS: The study included 316 patients (183 female and 133 male)
      that underwent surgery due to hip fracture and were followed up for >=1 year.
      Mean age of the male and female patients was 77.50 years (range; 65-95) and 78.23
      years (range; 65-100), respectively. The relationship between the RDW level at
      the time of presentation and mortality was evaluated. RESULTS: There was a
      significant relationship between mortality, and age (median age for man 77.50 and
      for woman 78.23) trochanteric fracture, and a high RDW level (>14.5%). In
      patients with these 3 characteristics the mortality rate was 2.8-fold higher than
      in the other patients. CONCLUSION: RDW is a parameter measured via routine blood
      testing. We think that RDW measurement should be used in the planning of the
      treatment of hip fractures and in scoring systems used to estimate post-operative
      mortality.

PMID- 24747621
TI  - Morphometry of the medial tibial plateau in Turkish knees: correlation to the
      current tibial components of unicompartmental knee arthroplasty.
AB  - OBJECTIVE: The objective of this study was to measure the resected surfaces of
      the tibia in knees of Turkish patients and to compare these measurements with the
      dimensions of tibial implants in current use. METHODS: We made measurements of
      seven different dimensions of the medial tibial plateau at the virtual resection
      level for unicompartmental knee arthroplasty (UKA) on MRIs of 260 patients and
      the most commonly used four UKA implants in Turkey. Statistical analysis was
      performed by using Student's t-test, analysis of variance (ANOVA), chi-square
      test and Pearson's correlation coefficient by using SPSS software. RESULTS: The
      anteroposterior and widest mediolateral dimensions of the tibial plateau of
      Turkish knees were found relatively more approximate to the dimensions of Oxford
      and Zuk prostheses compared to that of Accuris and Mitus (p<0.001). The distance
      between the central mediolateral dimension and the widest mediolateral dimension
      was 2.4 (range: 0-6.3) mm in males and 2.6 (range: 0-6.2) mm in females. The
      maximum mediolateral dimension was found posterior to the central mediolateral
      dimension in the majority (202 out of 260) of cases. These findings point towards
      the asymmetry in the AP halves of the resected medial tibial condyle. CONCLUSION:
      Tibial components designed according to anthropometric measurements based on both
      Western and Asian populations do not perfectly meet the requirements of Turkish
      population. Designing different UKA prostheses for different populations are
      required for best fit.

PMID- 24747622
TI  - [Treatment of thoracolumbar burst fractures using combined pedicle screw-laminar
      hook fixation].
AB  - OBJECTIVE: The aim of this study was to evaluate the mid-term outcome of pedicle
      screw-laminar hook (PS-LH) fixation in the surgical treatment of thoracolumbar
      burst fractures. METHODS: Nineteen patients (12 male, 7 female; mean age: 34.4
      years, range: 19 to 57 years) with thoracolumbar burst fractures treated using PS
      LH between 1996 and 2006 were evaluated. The 17 patients (11 male, 6 female) who
      had a minimum of 2 years follow-up were included in the study. Radiographic
      outcome was evaluated by measuring the local kyphosis angle (LKA) and anterior
      vertebral height (AVH). Mean follow-up was 81 (range: 38 to 122) months and 15
      patients completed more than 5 years of follow-up. RESULTS: Preoperative
      vertebral height loss and LKA of 41.2% (range: 29% to 64%) and 16.8 degrees 
      (range: 5 degrees  to 36 degrees ), respectively, were corrected to 16.3% (range:
      0% to 44%) and -1.2 degrees  (range: -17 degrees  to 10 degrees ), respectively,
      after the operation. Mean losses of correction for vertebral height and local
      kyphosis were 1.8 +/- 7.9% and 4.3 +/- 7.1 degrees, respectively, at the 2-year
      follow-up and -1.8 +/- 4.5% and 0.5 +/- 1.5 degrees, respectively, between 2
      years and 5 years. Loss of correction was significant for the LKA (p=0.023) but
      not for vertebral height (p=0.360). Five patients had losses of correction of
      more than 5 degrees. Changes between 2 and 5 years were not significant for
      vertebral height loss and local kyphosis (p=0.147 and p=0.205, respectively) and
      remained improved when compared with the preoperative values (p<0.001). Average
      SF-36 scores of the 15 patients evaluated at the final follow-up were comparable
      with the general Turkish population. CONCLUSION: The PS-LH construct provided a
      significant correction of the local kyphotic deformity. Augmentation of the upper
      and lower pedicle screw by the sublaminar hook did not completely prevent
      correction loss but was found to stabilize at the 5th year of follow-up without
      any clinical problems.

PMID- 24747623
TI  - Simultaneous bilateral lengthening of femora and tibiae in achondroplastic
      patients.
AB  - OBJECTIVE: The aim of this study was to analyze the results and complications of
      simultaneous bilateral femoral and tibial lengthening in achondroplastic
      patients. METHODS: The study included the 44 femora and 44 tibiae of 22
      achondroplastic patients (16 females, 6 males; mean age: 6.36 years, range: 3 to
      11 years) that underwent simultaneous lengthening. Orthofix LRS monolateral
      fixators were used for femoral lengthening and either Ilizarov-type or hexapod
      type circular external fixators for tibial lengthening. Tenotomies of the hip
      flexors and the Achilles tendon were performed to prevent injury to the growth
      plates and to prevent joint contractures. Results and complications were
      evaluated according to Paley's scoring and complication systems. RESULTS: Average
      follow-up time was 35 (range: 26 to 76) months. The femora were lengthened by an
      average of 7.07 cm (46.1%), and the tibiae by an average of 6.64 cm (52.9%).
      Patients gained an average of 16.9 cm in height, including physiological growth.
      The mean bone-healing index (BHI) was 31.2 days/cm for the femora (range: 17.4 to
      43.3 days/cm) and 34.3 days/cm for the tibiae (range: 19.5 to 60.0 days/cm).
      Complications included 3 delayed maturations, 3 pin track infections, 5 transient
      fibular paralyses, 5 regenerate fractures, 1 late varus deformity, 1 knee
      contracture and 1 knee contracture secondary to knee dislocation. Functional
      scores were excellent in 78 segments, good in 8, fair in 1 and poor in one. There
      was no growth inhibition related to the lengthening. CONCLUSION: Bilateral
      simultaneous lengthening of the femora and tibiae in achondroplastic patients
      provided a reduction in total treatment and external fixation time, with a low
      rate of complications.

PMID- 24747624
TI  - Flexion-adduction-external rotation method for shoulder dislocations.
AB  - OBJECTIVE: The aim of this prospective study was to assess the effectiveness of
      the flexion-adduction-external rotation method in the reduction of acute anterior
      shoulder dislocations. METHODS: The study included 128 patients (98 male, 30
      female; mean age: 33, range: 19 to 81) with a history of acute anterior shoulder
      dislocation treated with the flexion-adduction-external rotation method.
      Neurovascular examination was performed before and after reduction. Reduction
      duration and patient responses regarding the reduction method were recorded.
      RESULTS: First-time dislocation occurred in 92 patients and recurrent dislocation
      in 36. 111 patients had subcoracoid dislocations and 17 subglenoid dislocations.
      Fracture of the greater tubercle was present in 13 patients. Reduction was
      achieved in the first attempt in 104 patients and in the second in 12 patients.
      Mean reduction time was under 1.5 (range: 0 to 5) minutes. Reduction was
      unsuccessful in 12 patients and reduction under general anesthesia was performed.
      No patients experienced neurovascular injury after reduction. CONCLUSION: The
      forward flexion-adduction-external rotation method is an effective and
      comfortable reduction method for the treatment of shoulder dislocation or
      fracture-dislocation.

PMID- 24747625
TI  - Clinical evaluation of the anterior translation of glenohumeral joint using
      ultrasonography: an intra- and inter-rater reliability study.
AB  - OBJECTIVE: The aim of this study was to investigate the intra- and inter-rater
      reliability of ultrasonography (US) to measure anterior translation of the
      humeral head (ATHH) among healthy subjects and patients with sacroiliac joint
      dysfunction. METHODS: The study included a total of 22 shoulder joints from 11
      subjects. Six subjects were healthy and 5 had sacroiliac joint dysfunction.
      Anterior translation of the humeral head was measured twice using US by two
      different investigators. Intraclass correlation coefficient (ICC3,1), standard
      error of measurements (SEMs), coefficient of variations (CVs) and Bland-Altman
      plot were used as analytical tests to investigate intra- and inter-rater
      reliability, amount of error and agreeability of the measurements between
      investigators. RESULTS: Intraclass correlation coefficient was 0.94, showing a
      high level of intra-rater reliability of the first investigator with SEMs (0.01
      cm) and CV (5.1%) in measuring ATHH. Intra-rater reliability of the second
      investigator was 0.84 with SEMs (0.03 cms) and CV (9.6%), indicating a high level
      of reliability. Inter-rater reliability was high, with an ICC value of 0.92 with
      SEMs (0.02 cms) and CV (5.9%). CONCLUSION: The use of US as a measurement of ATHH
      has good levels of intra- and inter-rater reliability in clinical practice.

PMID- 24747626
TI  - Management of tennis elbow with topical glyceryl trinitrate.
AB  - OBJECTIVE: The aim of this study was to evaluate the treatment results of the
      application of nitric oxide (NO) in the form of topical glyceryl trinitrate (GTN)
      for the treatment of lateral epicondylitis (LE). METHODS: The study included 40
      patients with LE randomized into 2 equal groups. Selection criteria included the
      presence of pain, tenderness, and positive pain stimulating maneuvers. Glyceryl
      trinitrate patches were applied to the area of maximal tenderness once a day in
      the treatment group and placebo patches in the control group. Outcomes in terms
      of pain relief was assessed using the visual analog scale (VAS) and were
      evaluated according to the criteria of Verhaar et al. Excellent or good results
      were considered successful. Differences in VAS scores between the two groups were
      calculated using the Mann-Whitney U-test and the chi-square test was used to
      investigate distributions of categorical variables (sex, affected side) and good
      and excellent results among groups. RESULTS: There were no significant
      differences in any of the baseline clinical parameters between groups. At the 3rd
      week follow-up, there were statistically significant differences in the pain
      measured using VAS between groups (mean VAS score of the control and treatment
      groups were 6.45 and 3.15, respectively) (p=0.001). Patients in the GTN group and
      control group had lower VAS pain scores and reduced elbow pain at 3 weeks (3.15
      vs 8.05 in the GTN and 6.45 vs 8.80 in the control group). In the control group,
      no patient had excellent or good results while 18 (90%) patients in treatment
      group reported successful treatment. There was statistically significant
      difference in the VAS measured at 6 months between groups (mean VAS score of the
      control and treatment groups were 4.85 and 0.70, respectively) (p=0.001).
      CONCLUSION: The administration of NO directly over an area of tendinopathy
      through a GTN patch reduces pain and other symptoms in chronic LE.

PMID- 24747627
TI  - Surgical reconstruction in Wassel type IV thumb duplication.
AB  - OBJECTIVE: The aim of this study was to review the results of patients with
      Wassel type IV thumb duplication, treated with a single reconstructive procedure.
      METHODS: The mean follow-up period was 76.9 months. Objective assessments were
      carried out using Horii modification of Tada scoring system and ALURRA scoring
      system. Thumb length, thumb girth, range of motion of metacarpophalangeal (MCP)
      and interphalangeal (IP) joints and angular deformities at MCP and IP joints were
      evaluated. RESULTS: The mean ALURRA score was 21 (range; 16-24) and Tada Score
      5.25 (range; 2-7). The length of the operated thumb was approximately 95%, the
      girth 89% and nail width 80% of the non-operated side. The mean range of motion
      was 75.1% of the unaffected thumb in interphalangeal joint and 80.1% in
      metacarpophalangeal joint. Metacarpophalangeal joint malalignment had shown
      statistically significant negative correlation with the scores of Tada, ALURRA
      and VAS. CONCLUSION: Surgical reconstruction may provide a functional and stable
      thumb in Wassel type IV thumb duplications. The satisfaction of patients is
      affected by angular deformity of thumbs and cosmetic outlook.

PMID- 24747628
TI  - Mesenchymal stem cell application improves tendon healing via anti-apoptotic
      effect (Animal study).
AB  - OBJECTIVE: The aim of this study was to determine the effects of mesenchymal stem
      cell (MSC) application and the possible pathways of MSC's effects on tendon
      strength and healing after tendon repair. METHODS: The study included 40 Wistar
      albino rats. Mesenchymal stem cells were obtained from the femurs and tibias of 6
      rats. Achilles tendons of the remaining 34 rats were cut and repaired with open
      surgical procedures. Rats were divided into 2 groups. Percutaneous MSCs were
      applied to the study group (n=17) and physiological serum only was applied to the
      control group (n=17) at the 4th week. Rats were sacrificed using the cervical
      dislocation method under ether anesthesia at the 12th week and samples were
      analyzed by histological and immunohistochemical methods. For biomechanical
      analysis, a traction force was applied at 10 mm/min and load to failure was
      recorded for each specimen in Newtons. RESULTS: Histologically, there was no
      significant difference between groups (p>0.05). In the immunohistochemical
      studies, MSCs were located more intensively at the repair zone. Apoptosis was
      minimally present in the study group and was clearly increased in the control
      group. Increase in tendon strength was significantly higher in the study group
      than in the control group at the 12th week (p<0.05). CONCLUSION: The application
      of MSCs to decrease re-ruptures has a positive effect on tendon strength,
      probably due to their anti-apoptotic effects. Mesenchymal stem cell application
      can be used percutaneously and is effective in clinical practice in the late
      stages of tendon healing.

PMID- 24747629
TI  - Biomechanical comparison of antirotator compression hip screw and cannulated
      screw fixations in the femoral neck fractures.
AB  - OBJECTIVE: The aim of this study was to compare the biomechanical properties of
      minimal invasive sliding antirotator compressive hip screw (MIS-A-CHS), and
      multiple cannulated screws (CS) on a Pauwels type 3 femoral neck fracture model.
      METHODS: A Pauwels type 3 vertical femoral neck fractures was created on 12 third
      generation proximal femur models which were divided into two equal groups. The
      fracture was fixed with three CS in the first group, and MIS-A-CHS in the second
      group. The axial and rotational stiffness and maximum compression effect were
      compared between the groups. RESULTS: The axial and rotational stiffness and
      maximum compression were significantly higher in MIS-A-CHS group (912.5 N, 540 N
      and 10.2 N/m, respectively) than the CS group (627.5 N, 380 N, and 3.9 N/m,
      respectively). CONCLUSION: MIS-A-CHS appears to be a more secure fixation method
      in Pauwels type 3 femoral neck fractures than the CS.

PMID- 24747630
TI  - Restoration of pull-out strength of the failed pedicle screw: biomechanical
      comparison of calcium sulfate vs polymethylmethacrylate augmentation.
AB  - OBJECTIVE: The aim of the present study was to compare calcium sulfate (CAS) and
      polymethylmethacrylate (PMMA) bone cements used for the augmentation of a failed
      pedicle screw with biomechanical pull-out strength (POS) testing. METHODS: Thirty
      lumbar vertebrae were harvested from 6 calves and bone mineral densities (BMD)
      were measured. Primary polyaxial pedicle screws were randomly inserted and pulled
      out and the POSs of the specimen were recorded. For revision, specimens were
      randomly assigned to the CAS-augmented pedicle screws group (Group 1) or PMMA
      augmented pedicle screw group (Group 2). Pull-out tests were repeated to compare
      both groups. RESULTS: Mean BMD of the specimens was 1.006 +/- 0.116 g/cm(2).
      There were no statistically significant differences between BMD results of the
      two groups (p=0.116). For Group 1, mean POS of primary screws was 2,441.3 +/-
      936.4 N and was 2,499.5 +/- 1,425.1 N after CAS augmentation, demonstrating no
      statistically significant difference (p=0.865). In Group 2, mean POS of the
      primary screws was 2,876.6 +/- 926.6 N and significantly increased to 3,745.5 +/-
      1,299.2 N after PMMA augmentation (p=0.047). There was also a significant
      difference in mean POS between the CAS and PMMA groups (p=0.026). CONCLUSION:
      Although CAS augmentation facilitates a revision screw POS as strong as that of
      primary screws, it is not as strong as PMMA augmentation.

PMID- 24747631
TI  - Robotic hip arthroscopy: a cadaveric feasibility study.
AB  - OBJECTIVE: The aim of this study was to test if robotic surgery can be used while
      performing hip arthroscopy. METHODS: Hip arthroscopy was performed on two hip
      joints of a fresh-frozen male human cadaver. The arthroscopic control of the
      femoral head and neck and acetabular labrum were evaluated using the da Vinci
      Surgical System. RESULTS: Docking of the robotic system and manipulation of the
      instruments were successful. Although most regions reached in standard
      arthroscopy were also reached with this robotic setting, the 5-mm instrument was
      limited in movement due to its long articulation section. The 8-mm instrument had
      shorter articulation section and exhibited a full range of motion inside the
      joints. The posterior part of the femoral head and the posteroinferior portion of
      the acetabular labrum could not be observed because of the rigidity of the
      equipment. CONCLUSION: Robotic hip arthroscopy appears feasible in a cadaveric
      model but has some significant limitations. With the development of special
      instrumentations, arthroscopy of the large or small joints may be possible with
      robotic surgery. Robotic surgery may also enable surgeons to perform more complex
      and precise tasks in restricted spaces.

PMID- 24747632
TI  - Effects of enoxaparin and rivaroxaban on tissue survival in skin degloving
      injury: an experimental study.
AB  - OBJECTIVE: The aim of this study was to evaluate the effects of the
      antithrombotic agents enoxaparin and rivaroxaban on tissue survival following
      skin degloving injury in an experimental rat tail model. METHODS: The study
      included 24 rats divided into three equal groups of 8; the enoxaparin group
      (Group 1), the rivaroxaban group (Group 2) and the saline control group (Group
      3). A degloving injury was created by making a circular incision 5 cm distal to
      the base of the tail; manual traction was applied to the tail skin distal to the
      incision. After 15 minutes, the ends of the incision were sutured back in place.
      Antithrombotic agents were administered immediately after suturing and repeated
      once a day for 15 days. At the end of Day 15, the experiment was terminated.
      Gross morphological tissue survival and histopathology were evaluated. RESULTS:
      Histopathological examination of the enoxaparin and rivaroxaban groups revealed
      that the skin was mostly normal or intact with minimal inflammation. The mean
      length of necrotic area was significantly higher in the saline group compared to
      the enoxaparin and rivaroxaban groups (p<0.05). No statistically significant
      differences were noted between the rivaroxaban and enoxaparin groups (p=0.451).
      The mean extent of skin necrosis was significantly higher in the control group
      than the study groups (p<0.05), while there was no significant difference in the
      length of necrotic area between Group 1 and 2 (p=0.722). CONCLUSION: Rivaroxaban
      and enoxaparin improved tissue survival in skin degloving injuries in terms of
      gross morphological and histopathological findings in a rat tail model.

PMID- 24747633
TI  - Preventive effects of coenzyme Q10 (CoQ10) on steroid-induced osteonecrosis in
      rats.
AB  - OBJECTIVE: The aim of this study was to examine the role of coenzyme Q10 (CoQ10)
      in the prevention of steroid-induced osteonecrosis of the femoral head (ONFH) in
      rats. METHODS: The study included 20 Sprague-Dawley rats injected once with 20
      mg/kg of methylprednisolone acetate into the right gluteus medius muscle to
      induce osteonecrosis. Animals were divided into two equal groups; Group 1
      received no prophylaxis (control group) and the Group 2 received CoQ10.
      Hematological examinations were performed before steroid injection (0 weeks) and
      at 4 weeks after steroid injection. Femoral heads were examined histologically to
      evaluate osteonecrosis. RESULTS: Changes in blood glutathione (GSH) and
      malondialdehyde (MDA) concentrations were less significant in the CoQ10 group.
      The incidence of histologic changes consistent with early osteonecrosis was lower
      in the CoQ10 group (2 of 10; 20%) than the control group (7 of 10; 70%).
      CONCLUSION: Coenzyme Q10 may be useful as a preventing agent in steroid-induced
      ONFH. Inhibited oxidative stress is a possible mechanism for this effect.

PMID- 24747634
TI  - A novel method for the removal of distal part of broken intramedullary femoral
      nail.
AB  - We describe a new technique for the removal of the distal part of a broken
      intramedullary interlocking femoral nail. The distal part of the nail is pushed
      outward with the help of a antegradely driven new nail. This method is simple,
      less time consuming and requires only a Kuntscher's nail and a guidewire which
      are easily available in the operating rooms.

PMID- 24747635
TI  - Traumatic hemipelvectomy: case presentation.
AB  - Traumatic hemipelvectomy is a severe, life-threatening injury, mainly occurring
      due to machinery injury or traffic accident. Few cases have been published in the
      literature. Treatment requires a rapid, multidisciplinary team approach which
      will result in the saving of the patient's life. We present the outcome of a male
      patient with traumatic hemipelvectomy.

PMID- 24747636
TI  - Neglected patellar tendon rupture with anterior cruciate ligament rupture and
      medial collateral ligament partial rupture.
AB  - Anterior cruciate ligament injuries are common, mostly occurring during sports
      trauma. Conversely, patellar tendon ruptures are uncommon injuries secondary to
      forceful contractions of the extensor mechanism. It is important to consider the
      possibility of combined injuries around the knee. We present a case of neglected
      patellar tendon rupture with anterior cruciate ligament and medial collateral
      ligament rupture treated with arthroscopic anterior cruciate ligament
      reconstruction combined with patellar tendon reconstruction.

PMID- 24747637
TI  - Osteochondroma of the talus: an unusual location.
AB  - Osteochondroma rarely affects talus although it is the most common primary bone
      tumor. We report a case of talar osteochondroma in a 6 year-old boy. There was no
      recurrence two years after the local resection of the lesion. 

PMID- 24747638
TI  - Imaging plasma membrane deformations with pTIRFM.
AB  - To gain novel insights into the dynamics of exocytosis, our group focuses on the
      changes in lipid bilayer shape that must be precisely regulated during the fusion
      of vesicle and plasma membranes. These rapid and localized changes are achieved
      by dynamic interactions between lipids and specialized proteins that control
      membrane curvature. The absence of such interactions would not only have
      devastating consequences for vesicle fusion, but a host of other cellular
      functions that involve control of membrane shape. In recent years, the identity
      of a number of proteins with membrane-shaping properties has been determined.
      What remains missing is a roadmap of when, where, and how they act as fusion and
      content release progress. Our understanding of the molecular events that enable
      membrane remodeling has historically been limited by a lack of analytical methods
      that are sensitive to membrane curvature or have the temporal resolution to track
      rapid changes. PTIRFM satisfies both of these criteria. We discuss how pTIRFM is
      implemented to visualize and interpret rapid, submicron changes in the
      orientation of chromaffin cell membranes during dense core vesicle (DCV) fusion.
      The chromaffin cells we use are isolated from bovine adrenal glands. The membrane
      is stained with a lipophilic carbocyanine dye,1,1'-dioctadecyl-3,3,3',3'
      tetramethylindodicarbocyanine, 4-chlorobenzenesulfonate, or diD. DiD intercalates
      in the membrane plane with a "fixed" orientation and is therefore sensitive to
      the polarization of the evanescent field. The diD-stained cell membrane is
      sequentially excited with orthogonal polarizations of a 561 nm laser (p-pol, s
      pol). A 488 nm laser is used to visualize vesicle constituents and time the
      moment of fusion. Exocytosis is triggered by locally perfusing cells with a
      depolarizing KCl solution. Analysis is performed offline using custom-written
      software to understand how diD emission intensity changes relate to fusion pore
      dilation. 

PMID- 24747639
TI  - Mutations in CCNO result in congenital mucociliary clearance disorder with
      reduced generation of multiple motile cilia.
AB  - Using a whole-exome sequencing strategy, we identified recessive CCNO (encoding
      cyclin O) mutations in 16 individuals suffering from chronic destructive lung
      disease due to insufficient airway clearance. Respiratory epithelial cells showed
      a marked reduction in the number of multiple motile cilia (MMC) covering the cell
      surface. The few residual cilia that correctly expressed axonemal motor proteins
      were motile and did not exhibit obvious beating defects. Careful subcellular
      analyses as well as in vitro ciliogenesis experiments in CCNO-mutant cells showed
      defective mother centriole generation and placement. Morpholino-based knockdown
      of the Xenopus ortholog of CCNO also resulted in reduced MMC and centriole
      numbers in embryonic epidermal cells. CCNO is expressed in the apical cytoplasm
      of multiciliated cells and acts downstream of multicilin, which governs the
      generation of multiciliated cells. To our knowledge, CCNO is the first reported
      gene linking an inherited human disease to reduced MMC generation due to a defect
      in centriole amplification and migration.

PMID- 24747640
TI  - Triplication of a 21q22 region contributes to B cell transformation through HMGN1
      overexpression and loss of histone H3 Lys27 trimethylation.
AB  - Down syndrome confers a 20-fold increased risk of B cell acute lymphoblastic
      leukemia (B-ALL), and polysomy 21 is the most frequent somatic aneuploidy among
      all B-ALLs. Yet the mechanistic links between chromosome 21 triplication and B
      ALL remain undefined. Here we show that germline triplication of only 31 genes
      orthologous to human chromosome 21q22 confers mouse progenitor B cell self
      renewal in vitro, maturation defects in vivo and B-ALL with either the BCR-ABL
      fusion protein or CRLF2 with activated JAK2. Chromosome 21q22 triplication
      suppresses histone H3 Lys27 trimethylation (H3K27me3) in progenitor B cells and B
      ALLs, and 'bivalent' genes with both H3K27me3 and H3K4me3 at their promoters in
      wild-type progenitor B cells are preferentially overexpressed in triplicated
      cells. Human B-ALLs with polysomy 21 are distinguished by their overexpression of
      genes marked with H3K27me3 in multiple cell types. Overexpression of HMGN1, a
      nucleosome remodeling protein encoded on chromosome 21q22 (refs. 3,4,5),
      suppresses H3K27me3 and promotes both B cell proliferation in vitro and B-ALL in
      vivo.

PMID- 24747644
TI  - Structural modeling of djenkolic acid with sulfur replaced by selenium and
      tellurium.
AB  - The comparative structural modeling of djenkolic acid and its derivatives
      containing selenium and tellurium in chalcogen sites (Ch=Se, Te) has provided
      detailed information about the bond lengths and bond angles, filling the gap in
      what we know about the structural characteristics of these aminoacids. The
      investigation using the molecular mechanics technique with good approximation
      confirmed the available information on X-ray refinements for the related
      compounds methionine and selenomethionine, as well as for an estimate made
      earlier for telluromethionine. It was shown that the Ch-C(3) and Ch-C(4) bond
      lengths grow in parallel with the increasing anionic radii. Although the
      distances C-C, C-O, and C-N are very similar, the geometry of conformers is quite
      different owing to the possibility of rotation about four carbon atoms, hence the
      remarkable variability observed in dihedral angles. It was shown that the
      compounds contain a rigid block with two Ch atoms connected through a methylene
      group. The standard program Gaussian 03 with graphical interface Gaussview 4.1.2
      has proved to be satisfactory tool for the structural description of less-common
      bioactive compositions when direct X-ray results are absent.

PMID- 24747641
TI  - De novo mutations in HCN1 cause early infantile epileptic encephalopathy.
AB  - Hyperpolarization-activated, cyclic nucleotide-gated (HCN) channels contribute to
      cationic Ih current in neurons and regulate the excitability of neuronal
      networks. Studies in rat models have shown that the Hcn1 gene has a key role in
      epilepsy, but clinical evidence implicating HCN1 mutations in human epilepsy is
      lacking. We carried out exome sequencing for parent-offspring trios with fever
      sensitive, intractable epileptic encephalopathy, leading to the discovery of two
      de novo missense HCN1 mutations. Screening of follow-up cohorts comprising 157
      cases in total identified 4 additional amino acid substitutions. Patch-clamp
      recordings of Ih currents in cells expressing wild-type or mutant human HCN1
      channels showed that the mutations had striking but divergent effects on
      homomeric channels. Individuals with mutations had clinical features resembling
      those of Dravet syndrome with progression toward atypical absences, intellectual
      disability and autistic traits. These findings provide clear evidence that de
      novo HCN1 point mutations cause a recognizable early-onset epileptic
      encephalopathy in humans.

PMID- 24747643
TI  - Recurrent activating mutation in PRKACA in cortisol-producing adrenal tumors.
AB  - Adrenal tumors autonomously producing cortisol cause Cushing's syndrome. We
      performed exome sequencing of 25 tumor-normal pairs and identified 2 subgroups.
      Eight tumors (including three carcinomas) had many somatic copy number variants
      (CNVs) with frequent deletion of CDC42 and CDKN2A, amplification of 5q31.2 and
      protein-altering mutations in TP53 and RB1. Seventeen tumors (all adenomas) had
      no somatic CNVs or TP53 or RB1 mutations. Six of these had known gain-of-function
      mutations in CTNNB1 (beta-catenin) or GNAS (Galphas). Six others had somatic
      mutations in PRKACA (protein kinase A (PKA) catalytic subunit) resulting in a
      p.Leu206Arg substitution. Further sequencing identified this mutation in 13 of 63
      tumors (35% of adenomas with overt Cushing's syndrome). PRKACA, GNAS and CTNNB1
      mutations were mutually exclusive. Leu206 directly interacts with the regulatory
      subunit of PKA, PRKAR1A. Leu206Arg PRKACA loses PRKAR1A binding, increasing the
      phosphorylation of downstream targets. PKA activity induces cortisol production
      and cell proliferation, providing a mechanism for tumor development. These
      findings define distinct mechanisms underlying adrenal cortisol-producing tumors.

PMID- 24747642
TI  - Integrated genomic characterization of adrenocortical carcinoma.
AB  - Adrenocortical carcinomas (ACCs) are aggressive cancers originating in the cortex
      of the adrenal gland. Despite overall poor prognosis, ACC outcome is
      heterogeneous. We performed exome sequencing and SNP array analysis of 45 ACCs
      and identified recurrent alterations in known driver genes (CTNNB1, TP53, CDKN2A,
      RB1 and MEN1) and in genes not previously reported in ACC (ZNRF3, DAXX, TERT and
      MED12), which we validated in an independent cohort of 77 ACCs. ZNRF3, encoding a
      cell surface E3 ubiquitin ligase, was the most frequently altered gene (21%) and
      is a potential new tumor suppressor gene related to the beta-catenin pathway. Our
      integrated genomic analyses further identified two distinct molecular subgroups
      with opposite outcome. The C1A group of ACCs with poor outcome displayed numerous
      mutations and DNA methylation alterations, whereas the C1B group of ACCs with
      good prognosis displayed specific deregulation of two microRNA clusters. Thus,
      aggressive and indolent ACCs correspond to two distinct molecular entities driven
      by different oncogenic alterations.

PMID- 24747645
TI  - Identification of absorbed constituents in the rabbit plasma and cerebrospinal
      fluid after intranasal administration of Asari Radix et Rhizoma by HS-SPME-GC-MS
      and HPLC-APCI-IT-TOF-MSn.
AB  - Traditional Chinese Medicine (TCM) nasal therapy has been utilized to treat
      numerous diseases for over two millennia. It has many advantages compared with
      other routes. In this article, headspace-solid phase microextraction-gas
      chromatography-mass spectrometry and high performance liquid chromatography
      atmospheric pressure chemical ionization-ion trap-time of flight-multistage mass
      spectrometry were applied for the first time to analyze the absorbed constituents
      in rabbit plasma and cerebrospinal fluid (CSF) after intranasal administration of
      Asari Radix et Rhizoma (AR). In total, 47 absorbed AR constituents including 14
      monoterpenes, 10 phenylpropanoids, four benzene derivatives, two alkanes, nine N
      alkylamides and eight lignans were tentatively identified in the rabbit plasma
      and CSF. Thirty-three absorbed constituents are found to have different
      bioactivities related to the pharmacological actions of AR through bibliography
      data retrieval. These indicated that many types of constituents of TCM can be
      absorbed at the nasal cavity into both rabbit blood and CSF. This is the first
      study to explore the absorption of AR, and comprehensively analyze the absorbed
      constituents after intranasal administration of TCM. These findings extend our
      understanding of the effective substances of AR, and inspire us to make a
      hypothesis on the mechanism of additive effect of multiple constituents of TCMs,
      which is very worthy of further investigation. 

PMID- 24747646
TI  - Kinetics of glycoxidation of bovine serum albumin by methylglyoxal and glyoxal
      and its prevention by various compounds.
AB  - The aim of this study was to compare several methods for measurement of bovine
      serum albumin (BSA) modification by glycoxidation with reactive dicarbonyl
      compounds (methylglyoxal--MGO and glyoxal--GO), for studies of the kinetics of
      this process and to compare the effects of 19 selected compounds on BSA glycation
      by the aldehydes. The results confirm the higher reactivity of MGO with respect
      to GO and point to the usefulness of AGE, dityrosine and N'-formylkynurenine
      fluorescence for monitoring glycation and evaluation of protection against
      glycation. Different extent of protection against glycation induced by MGO and GO
      was found for many compounds, probably reflecting effects on various stages of
      the glycation process. Polyphenols (genistein, naringin and ellagic acid) were
      found to protect against aldehyde-induced glycation; 1-cyano-4-hydroxycinnamic
      acid was also an effective protector.

PMID- 24747647
TI  - Three new ring-A modified ursane triterpenes from Davidia involucrata.
AB  - Three new ursane triterpenes, 3alpha,19alpha-dihydroxy-2-nor-urs-12-en-23,28
      dioic acid-23-methyl ester (1), 19alpha,23-dihydroxy-3-oxo-2-nor-urs-12-en-28-oic
      acid (2), and 2,3-seco-3-methoxy-3,19alpha,23-trihydroxy-urs-12-en-2-al-28-oic
      acid (3), were isolated from the MeOH extract of the branch barks of Davidia
      involucrata, together with six known compounds. Their structures were elucidated
      by means of various spectroscopic analyses. The isolated triterpenes provide
      important evolutionary and chemotaxonomic knowledge about the monotypic genus
      Davidia. Five of the identified compounds showed moderate cytotoxicities against
      the cell proliferation of SGC-7901, MCF-7, and BEL-7404 with IC50 range from 7.26
      to 47.41 MUM. 

PMID- 24747648
TI  - Enantioselective separation of mirtazapine and its metabolites by capillary
      electrophoresis with acetonitrile field-amplified sample stacking and its
      application.
AB  - A simple, rapid and sensitive chiral capillary zone electrophoresis coupled with
      acetonitrile-field-amplified sample stacking method was developed that allows the
      simultaneous enantioselective separation of the mirtazapine, N
      demethylmirtazapine, 8-hydroxymirtazapine and mirtazapine-N-oxide. The separation
      was achieved on an uncoated 40.2 cm*75 MUM fused silica capillary with an applied
      voltage of 16 kV. The electrophoretic analyses were carried out in 6.25 mM borate
      25 mM phosphate solution at pH 2.8 containing 5.5 mg/mL carboxymethyl-beta
      cyclodextrin. The detection wavelength was 200 nm. Under these optimized
      conditions, satisfactory chiral separations of four pair enantiomers were
      achieved in less than 7 min in vitro. After one step clean-up liquid-liquid
      extraction using 96-well format, sample was introduced capillary zone
      electrophoresis with acetonitrile-field-amplified sample stacking to enhance the
      sensitivity of enantiomers. The method was validated with respect to specificity,
      linearity, lower limit of quantitation, accuracy, precision, extraction recovery
      and stability. The lower limit of quantification was 0.5 ng/mL with linear
      response over the 0.5-50 ng/mL concentration range for each mirtazapine, N
      demethylmirtazapine and 8-hydroxymirtazapine enantiomer. The developed and
      validated method has been successfully applied to the enantioselective
      pharmacokinetic studies in 12 healthy volunteers after oral administration of rac
      mirtazapine.

PMID- 24747649
TI  - The synergistic biologic activity of oleanolic and ursolic acids in complex with
      hydroxypropyl-gamma-cyclodextrin.
AB  - Oleanolic and ursolic acids are natural triterpenic compounds with pentacyclic
      cholesterol-like structures which gives them very low water solubility, a
      significant disadvantage in terms of bioavailability. We previously reported the
      synthesis of inclusion complexes between these acids and cyclodextrins, as well
      as their in vivo evaluation on chemically induced skin cancer experimental
      models. In this study the synergistic activity of the acid mixture included
      inside hydroxypropyl-gamma-cyclodextrin (HPGCD) was monitored using in vitro
      tests and in vivo skin cancer models. The coefficient of drug interaction (CDI)
      was used to characterize the interactions as synergism, additivity or antagonism.
      Our results revealed an increased antitumor activity for the mixture of the two
      triterpenic acids, both single and in complex with cyclodextrin, thus proving
      their complementary biologic activities. 

PMID- 24747650
TI  - Anti-proliferative and apoptosis-inducing effects of camptothecin-20(s)-O-(2
      pyrazolyl-1)acetic ester in human breast tumor MCF-7 cells.
AB  - Camptothecin-20(s)-O-(2-pyrazolyl-1)acetic ester (CPT6) is a novel semi-synthetic
      analog of camptothecin. In a previous report, CPT6 possessed higher cytotoxic
      activity in vitro towards human breast tumor MCF-7 cells than topotecan. In this
      study, the antitumor activity of CPT6 on the human breast tumor MCF-7 cell line
      was analyzed using the MTT method. The underlying mechanism of CPT6 action was
      investigated by analyzing the cell cycle distribution, apoptotic proportion,
      changes in mitochondrial membrane potential, and intracellular Ca2+ concentration
      using flow cytometry. Nuclear and mitochondrial morphologies were also observed
      by laser scanning confocal and transmission electron microscopy. DNA damage was
      observed in MCF-7 cells treated with CPT6. Low-dose CPT6 had a significant
      cytotoxic effect and could inhibit proliferation and induce apoptosis in MCF-7
      cells, possibly through cell nucleus fragmentation and DNA damage. CPT6 thus
      appears to display potent antitumor activity against human breast tumor MCF-7
      cells via the induction of apoptosis, and may be a useful alternative drug for
      breast cancer therapy. 

PMID- 24747651
TI  - Characterization of natural aryl hydrocarbon receptor agonists from cassia seed
      and rosemary.
AB  - Many recent studies have suggested that activation of the aryl hydrocarbon
      receptor (AhR) reduces immune responses, thus suppressing allergies and
      autoimmune diseases. In our continuing study on natural AhR agonists in foods, we
      examined the influence of 37 health food materials on the AhR using a reporter
      gene assay, and found that aqueous ethanol extracts of cassia seed and rosemary
      had particularly high AhR activity. To characterize the AhR-activating substances
      in these samples, the chemical constituents of the respective extracts were
      identified. From an active ethyl acetate fraction of the cassia seed extract,
      eight aromatic compounds were isolated. Among these compounds, aurantio-obtusin,
      an anthraquinone, elicited marked AhR activation. Chromatographic separation of
      an active ethyl acetate fraction of the rosemary extract gave nine compounds.
      Among these compounds, cirsimaritin induced AhR activity at 10-102 MUM, and
      nepitrin and homoplantagenin, which are flavone glucosides, showed marked AhR
      activation at 10-103 MUM.

PMID- 24747652
TI  - Does robotic assistance confer an economic benefit during laparoscopic radical
      nephrectomy?
AB  - PURPOSE: While robotic assisted radical nephrectomy is safe with outcomes and
      complication rates comparable to those of the pure laparoscopic approach, there
      is little evidence of an economic or clinical benefit. MATERIALS AND METHODS:
      From the 2009 to 2011 Nationwide Inpatient Sample database we identified patients
      18 years old or older who underwent radical nephrectomy for primary renal
      malignancy. Robotic assisted and laparoscopic techniques were noted. Patients
      treated with the open technique and those with evidence of metastatic disease
      were excluded from analysis. Descriptive statistics were performed using the chi
      square and Mann-Whitney tests, and the Student t-test. Multiple linear regression
      was done to examine factors associated with increased hospital costs and charges.
      RESULTS: We identified 24,312 radical nephrectomy cases for study inclusion, of
      which 7,787 (32%) were performed robotically. There was no demographic difference
      between robotic assisted and pure laparoscopic radical nephrectomy cases. Median
      total charges were $47,036 vs $38,068 for robotic assisted vs laparoscopic
      surgery (p <0.001). Median total hospital costs for robotic assisted surgery were
      $15,149 compared to $11,735 for laparoscopic surgery (p <0.001). There was no
      difference in perioperative complications or the incidence of death. Compared to
      the laparoscopic approach robotic assistance conferred an estimated $4,565 and
      $11,267 increase in hospital costs and charges, respectively, when adjusted for
      adapted Charlson comorbidity index score, perioperative complications and length
      of stay (p <0.001). CONCLUSIONS: Robotic assisted radical nephrectomy results in
      increased medical expense without improving patient morbidity. Assuming surgeon
      proficiency with pure laparoscopy, robotic technology should be reserved
      primarily for complex surgeries requiring reconstruction. Traditional
      laparoscopic techniques should continue to be used for routine radical
      nephrectomy.

PMID- 24747653
TI  - Primary small cell carcinoma arising from a bladder diverticulum.

PMID- 24747654
TI  - Leaning in to understand hospital readmission.

PMID- 24747655
TI  - Chronic kidney disease due to surgical removal of nephrons: relative rates of
      progression and survival.
AB  - PURPOSE: Chronic kidney disease is associated with a higher likelihood of
      progression to end stage renal disease and increased mortality rates. However,
      the etiology of nephron loss may modify the rate of chronic kidney disease
      progression and overall survival. MATERIALS AND METHODS: Patients with suspected
      renal malignancy who had a new baseline glomerular filtration rate of less than
      60 ml/minute/1.73 m(2) 6 weeks after surgery were divided into the 2 groups of
      surgically induced chronic kidney disease (preoperative glomerular filtration
      rate greater than 60 ml/minute/1.73 m(2)) and preexisting chronic kidney disease
      due to medical causes followed by surgery. An independent cohort of subjects with
      chronic kidney disease entirely due to medical causes served as a comparator.
      RESULTS: Renal cancer surgery yielded cohorts with surgically induced chronic
      kidney disease (1,097) and chronic kidney disease due to medical causes followed
      by surgery (1,053), whereas the group with chronic kidney disease due to medical
      causes consisted of 42,658 subjects. The patients with chronic kidney disease due
      to medical causes and chronic kidney disease from medical causes followed by
      surgery were older compared to those with surgically induced chronic kidney
      disease, had more medical comorbidities and had a lower baseline glomerular
      filtration rate (all p <0.001). The group with chronic kidney disease due to
      medical causes followed by surgery had a lower mean (+/-SD) new baseline
      glomerular filtration rate (37+/-10) compared to the surgically induced chronic
      kidney disease (48+/-9) and chronic kidney disease due to medical comorbidities
      (47+/-10) groups (p <0.001). The probability of progressive decline in renal
      function (50% decrease in glomerular filtration rate or need for dialysis) at 3
      years was lowest for surgically induced chronic kidney disease, intermediate for
      chronic kidney disease from medical causes followed by surgery and highest for
      chronic kidney disease from medical causes when age, gender, race, comorbidities
      and new baseline glomerular filtration rate were considered (p <0.001). Nonrenal
      cancer related mortality was substantially lower for those with surgically
      induced chronic kidney disease compared to the other groups (p <0.001).
      CONCLUSIONS: Our data suggest that surgically induced chronic kidney disease has
      a lower rate of functional decline and less impact on survival than chronic
      kidney disease due to medical causes. These data have potential implications with
      respect to chronic kidney disease classification and patient counseling for
      surgical management of various renal disorders including renal cancer.

PMID- 24747656
TI  - Computerized tomography staging of renal tumors-does it make the surgeon
      obsolete?

PMID- 24747657
TI  - Clinical validation of an epigenetic assay to predict negative histopathological
      results in repeat prostate biopsies.
AB  - PURPOSE: The DOCUMENT multicenter trial in the United States validated the
      performance of an epigenetic test as an independent predictor of prostate cancer
      risk to guide decision making for repeat biopsy. Confirming an increased negative
      predictive value could help avoid unnecessary repeat biopsies. MATERIALS AND
      METHODS: We evaluated the archived, cancer negative prostate biopsy core tissue
      samples of 350 subjects from a total of 5 urological centers in the United
      States. All subjects underwent repeat biopsy within 24 months with a negative
      (controls) or positive (cases) histopathological result. Centralized blinded
      pathology evaluation of the 2 biopsy series was performed in all available
      subjects from each site. Biopsies were epigenetically profiled for GSTP1, APC and
      RASSF1 relative to the ACTB reference gene using quantitative methylation
      specific polymerase chain reaction. Predetermined analytical marker cutoffs were
      used to determine assay performance. Multivariate logistic regression was used to
      evaluate all risk factors. RESULTS: The epigenetic assay resulted in a negative
      predictive value of 88% (95% CI 85-91). In multivariate models correcting for
      age, prostate specific antigen, digital rectal examination, first biopsy
      histopathological characteristics and race the test proved to be the most
      significant independent predictor of patient outcome (OR 2.69, 95% CI 1.60-4.51).
      CONCLUSIONS: The DOCUMENT study validated that the epigenetic assay was a
      significant, independent predictor of prostate cancer detection in a repeat
      biopsy collected an average of 13 months after an initial negative result. Due to
      its 88% negative predictive value adding this epigenetic assay to other known
      risk factors may help decrease unnecessary repeat prostate biopsies.

PMID- 24747658
TI  - Modeling combined schizophrenia-related behavioral and metabolic phenotypes in
      rodents.
AB  - Schizophrenia is a chronic, debilitating disorder with a complex behavioral and
      cognitive phenotype underlined by a similarly complex etiology involving an
      interaction between susceptibility genes and environmental factors during early
      development. Limited progress has been made in developing novel pharmacotherapy,
      partly due to a lack of valid animal models. The recent recognition of the
      potentially causal role of central and peripheral energy metabolism in the
      pathophysiology of schizophrenia raises the need of research on animal models
      that combine both behavioral and metabolic phenotypic domains, similar to what
      have been identified in humans. In this review we focus on selected genetic
      (DBA/2J mice, leptin receptor mutants, and PSD-93 knockout mice), early
      neurodevelopmental (maternal protein deprivation) and pharmacological (acute
      phencyclidine) animal models that capture the combined behavioral and metabolic
      abnormalities shown by schizophrenic patients. In reviewing behavioral phenotypes
      relevant to schizophrenia we apply the principles established by the Research
      Domain Criteria (RDoC) for better translation. We demonstrate that etiologically
      diverse manipulations such as specific breeding, deletion of genes that are
      primarily involved in metabolic regulation and in synaptic plasticity, as well as
      early metabolic deprivation and adult pharmacological challenge of the glutamate
      system can lead to schizophrenia-related behavioral and metabolic phenotypes,
      which suggest that these pathways might be interlinked. We propose that using
      animal models that combine different domains of schizophrenia can be used as a
      translationally valid approach to capture the system-level complex interplay
      between peripheral and central processes in the development of psychopathology. 

PMID- 24747660
TI  - Novel ethological endophenotypes in a transgenic mouse model of Huntington's
      disease.
AB  - Huntington's disease (HD) is an autosomal dominant, neurodegenerative disorder
      with a characteristic triad of cognitive, affective and motor symptoms.
      Transgenic HD mice show excellent construct and face validity for many of these
      symptoms, however the decline in some facets of every day activity in humans is
      difficult to model. One approach is the assessment of species-relevant behaviors.
      Here we described three ethologically appropriate tests in the mouse-olfactory
      sensitivity, nest-building and sexually-motivated vocalizations. In R6/1 HD mice,
      olfactory and nest-building tests were sensitive to early dysfunctions induced by
      the HD mutation. Male vocalization testing revealed a late-stage sexual
      disinterest in R6/1 HD mice compared to WT littermates. We show that essential,
      species-relevant functions are disrupted by the HD mutation. The development of
      integrative behavioral assays which more closely model 'activities of daily
      living' (ADL) will facilitate the testing of novel therapeutic interventions in
      animal models as well as their clinical translation. 

PMID- 24747659
TI  - Sign-tracking to an appetitive cue predicts incubation of conditioned fear in
      rats.
AB  - Although post-traumatic stress disorder (PTSD) and addiction are very different
      disorders, both are characterized by hyperreactivity to trauma- or drug-related
      cues, respectively. We investigated whether an appetitive conditioning task,
      Pavlovian conditioned approach, which predicts vulnerability to reinstatement of
      cocaine-seeking, also predicts fear incubation, which may be a marker for
      vulnerability to PTSD. We classified rats based on whether they learned to
      approach and interact with a food predictive cue (sign-trackers), or, whether
      upon cue presentation they went to the location of impending food delivery (goal
      trackers). Rats were then exposed to extensive Pavlovian tone-shock pairings,
      which causes the fear response to increase or "incubate" over time. We found that
      the fear incubation effect was only present in sign-trackers. The behavior of
      goal-trackers was more consistent with a normal fear response-it was most robust
      immediately after training and decayed slowly over time. Sign-trackers also had
      lower levels of brain-derived neurotrophic factor (BDNF) protein in the
      prefrontal cortex than goal-trackers. These results indicate that, while many
      factors likely contribute to the disproportionate co-occurrence of PTSD and
      substance abuse, one such factor may be a core psychological trait that biases
      some individuals to attribute excessive motivational significance to predictive
      cues, regardless of the emotional valence of those cues. High levels of BDNF in
      the prefrontal cortex may be protective against developing excessive emotional
      and motivational responses to salient cues. 

PMID- 24747661
TI  - Conserved role of Drosophila melanogaster FoxP in motor coordination and
      courtship song.
AB  - FoxP2 is a highly conserved vertebrate transcription factor known for its
      importance in human speech and language production. Disruption of FoxP2 in
      several vertebrate models indicates a conserved functional role for this gene in
      both sound production and motor coordination. Although FoxP2 is known to be
      strongly expressed in brain regions important for motor coordination, little is
      known about FoxP2's role in the nervous system. The recent discovery of the well
      conserved Drosophila melanogaster homolog, FoxP, provides an opportunity to study
      the role of this crucial gene in an invertebrate model. We hypothesized that,
      like FoxP2, Drosophila FoxP is important for behaviors requiring fine motor
      coordination. We used targeted RNA interference to reduce expression of FoxP and
      assayed the effects on a variety of adult behaviors. Male flies with reduced FoxP
      expression exhibit decreased levels of courtship behavior, altered pulse-song
      structure, and sex-specific motor impairments in walking and flight. Acute
      disruption of synaptic activity in FoxP expressing neurons using a temperature
      sensitive shibire allele dramatically impaired motor coordination. Utilizing a
      GFP reporter to visualize FoxP in the fly brain reveals expression in relatively
      few neurons in distributed clusters within the larval and adult CNS, including
      distinct labeling of the adult protocerebral bridge - a section of the insect
      central complex known to be important for motor coordination and thought to be
      homologous to areas of the vertebrate basal ganglia. Our results establish the
      necessity of this gene in motor coordination in an invertebrate model and suggest
      a functional homology with vertebrate FoxP2. 

PMID- 24747663
TI  - New players in the fatty acyl ethanolamide metabolism.
AB  - Fatty acyl ethanolamides represent a class of endogenous bioactive lipid
      molecules and are generally referred to as N-acylethanolamines (NAEs). NAEs
      include palmitoylethanolamide (anti-inflammatory and analgesic substance),
      oleoylethanolamide (anorexic substance), and anandamide (endocannabinoid). The
      endogenous levels of NAEs are mainly regulated by enzymes responsible for their
      biosynthesis and degradation. In mammalian tissues, the major biosynthetic
      pathway starts from glycerophospholipids and is composed of two enzyme reactions.
      The first step is N-acylation of ethanolamine phospholipids catalyzed by Ca(2+)
      dependent N-acyltransferase and the second step is the release of NAEs from N
      acylated ethanolamine phospholipids by N-acylphosphatidylethanolamine (NAPE)
      hydrolyzing phospholipase D (NAPE-PLD). As for the degradation of NAEs, fatty
      acid amide hydrolase plays the central role. However, recent studies strongly
      suggest the involvement of other enzymes in the NAE metabolism. These enzymes
      include members of the HRAS-like suppressor family (also called phospholipase
      A/acyltransferase family), which were originally discovered as tumor suppressors
      but can function as Ca(2+)-independent NAPE-forming N-acyltransferases; multiple
      enzymes involved in the NAPE-PLD-independent multi-step pathways to generate NAE
      from NAPE, which came to light by the analysis of NAPE-PLD-deficient mice; and a
      lysosomal NAE-hydrolyzing acid amidase as a second NAE hydrolase. These newly
      recognized enzymes may become the targets for the development of new therapeutic
      drugs. Here, we focus on recent enzymological findings in this area. 

PMID- 24747662
TI  - Using pharmacological chaperones to restore proteostasis.
AB  - Normal organismal physiology depends on the maintenance of proteostasis in each
      cellular compartment to achieve a delicate balance between protein synthesis,
      folding, trafficking, and degradation while minimizing misfolding and
      aggregation. Defective proteostasis leads to numerous protein misfolding
      diseases. Pharmacological chaperones are cell-permeant small molecules that
      promote the proper folding and trafficking of a protein via direct binding to
      that protein. They stabilize their target protein in a protein-pharmacological
      chaperone state, increasing the natively folded protein population that can
      effectively engage trafficking machinery for transport to the final destination
      for function. Here, as regards the application of pharmacological chaperones, we
      focus on their capability to promote the folding and trafficking of lysosomal
      enzymes, G protein coupled receptors (GPCRs), and ion channels, each of which is
      presently an important drug target. Pharmacological chaperones hold great promise
      as potential therapeutics to ameliorate a variety of protein misfolding diseases.

PMID- 24747664
TI  - Measuring spinal presynaptic inhibition in mice by dorsal root potential
      recording in vivo.
AB  - Presynaptic inhibition is one of the most powerful inhibitory mechanisms in the
      spinal cord. The underlying physiological mechanism is a depolarization of
      primary afferent fibers mediated by GABAergic axo-axonal synapses (primary
      afferent depolarization). The strength of primary afferent depolarization can be
      measured by recording of volume-conducted potentials at the dorsal root (dorsal
      root potentials, DRP). Pathological changes of presynaptic inhibition are crucial
      in the abnormal central processing of certain pain conditions and in some
      disorders of motor hyperexcitability. Here, we describe a method of recording DRP
      in vivo in mice. The preparation of spinal cord dorsal roots in the anesthetized
      animal and the recording procedure using suction electrodes are explained. This
      method allows measuring GABAergic DRP and thereby estimating spinal presynaptic
      inhibition in the living mouse. In combination with transgenic mouse models, DRP
      recording may serve as a powerful tool to investigate disease-associated spinal
      pathophysiology. In vivo recording has several advantages compared to ex vivo
      isolated spinal cord preparations, e.g. the possibility of simultaneous recording
      or manipulation of supraspinal networks and induction of DRP by stimulation of
      peripheral nerves. 

PMID- 24747665
TI  - FOXO3 and related transcription factors in development, aging, and exceptional
      longevity.
AB  - In June 2013, a workshop was convened in San Francisco to explore, in depth, the
      role of the Forkhead transcription factor FOXO3 (and related FOXOs) in
      development, aging, and, in particular, exceptional longevity. The presentations
      covered results derived from model systems, computational analysis and
      bioinformatics, and genomics and genome-wide association studies of a number of
      cohorts. Although the data collectively strongly reinforce FOXO3 and the
      FOXO/FOXO3 pathway as very important determinants in aging and life span, much of
      the detail of how the latter is achieved still remains unknown, in part, because
      of the very large number of genes (~2,200 in Caenorhabditis elegans) the
      transcription factor is involved in helping regulate. Particularly challenging at
      the present time is understanding the association of apparently nonfunctional
      specific variants (single nucleotide polymorphisms) of FOXO3 and exceptional
      longevity in humans, a finding replicated in a number of studies. Nonetheless, as
      summarized in this report, valuable information and insights were presented at
      the workshop on the transcription factor including but not limited to its role in
      determining longevity in C elegans and Drosophila (in flies, eg, an important
      interaction in aging occurs between dFOXO and the transforming growth factor
      beta/activin pathway), stem cell function and aging (notably in hematopoiesis),
      downstream regulatory activity (eg, by binding near sites of RNAse occupancy and
      altering chromatin structure), and as a potential target for the development a
      healthy aging drug (in this example, using compounds developed and screened to
      effect FOXO function in cancer cells). 

PMID- 24747666
TI  - Targeting of DNA Damage Signaling Pathway Induced Senescence and Reduced
      Migration of Cancer cells.
AB  - The heat shock 70 family protein, mortalin, has pancytoplasmic distribution
      pattern in normal and perinuclear in cancer human cells. Cancer cells when
      induced to senesce by either chemicals or stress showed shift in mortalin
      staining pattern from perinuclear to pancytoplasmic type. Using such shift in
      mortalin staining as a reporter, we screened human shRNA library and identified
      nine senescence-inducing siRNA candidates. An independent Comparative Genomic
      Hybridization analysis of 35 breast cancer cell lines revealed that five (NBS1,
      BRCA1, TIN2, MRE11A, and KPNA2) of the nine genes located on chromosome regions
      identified as the gain of locus in more than 80% cell lines. By gene-specific
      PCR, these five genes were found to be frequently amplified in cancer cell lines.
      Bioinformatics revealed that the identified targets were connected to MRN (MRE11
      RAD50-NBS1) complex, the DNA damage-sensing complex. We demonstrate that the
      identified shRNAs triggered DNA damage response and induced the expression of
      tumor suppressor protein p16(INK4A) causing growth arrest of cancer cells.
      Furthermore, cells showed decreased migration, mediated by decrease in matrix
      metalloproteases. Taken together, we demonstrate that the MRN complex is a
      potential target of cancer cell proliferation and migration, and staining pattern
      of mortalin could serve as an assay to identify senescence-inducing/anticancer
      reagents. 

PMID- 24747667
TI  - Codeine-related deaths: The role of pharmacogenetics and drug interactions.
AB  - The objective of this study was to assess the relationship between genetic
      polymorphisms and drug interactions on codeine and morphine concentrations in
      codeine-related deaths (CRD). All CRD in Ontario, Canada between 2006 and 2008
      were identified. Post-mortem blood was analyzed for 22 polymorphisms in 5 genes
      involved in codeine metabolism and response. Sixty-eight CRD were included in
      this study. The morphine-to-codeine ratio was significantly correlated with the
      presence of a CYP2D6 inhibitor at varying potencies (p=0.0011). The presence of
      other central nervous system (CNS) depressants (i.e. benzodiazepines, hypnotics,
      and/or alcohol) was significantly associated with lower codeine concentration as
      compared to CRD in which other CNS depressants were not detected (p=0.0002).
      Individuals who carried the ABCB1 1236T variant had significantly lower morphine
      concentrations (p=0.004). In this population of individuals whose cause of death
      was related to codeine, drug interactions and genetic polymorphisms were
      significantly associated with post-mortem codeine and morphine concentrations. 

PMID- 24747668
TI  - Comparison of breath-alcohol screening test results with venous blood alcohol
      concentration in suspected drunken drivers.
AB  - Hand-held electronic breath-alcohol analyzers are widely used by police
      authorities in their efforts to detect drunken drivers and to improve road
      traffic safety. Over a three month period, the results of roadside breath-alcohol
      tests of drivers apprehended in Finland were compared with venous blood alcohol
      concentration (BAC). The mean (median) time between sampling blood and breath was
      0.71h (0.58h) with a range from 0 to 6h. Some hand-held instruments gave results
      as the concentration of alcohol in breath and were converted into BAC assuming a
      blood-breath alcohol ratio (BBR) of 2260. The mean venous BAC (1.82g/kg) in
      traffic offenders was higher than the result predicted by the hand-held breath
      analyzers (1.72g/kg). In 1875 roadside tests, the relationship between venous BAC
      (x) and BrAC (y) was defined by the regression equation y=0.18+0.85x. The
      coefficients show both a constant bias (y-intercept 0.18g/kg) and a proportional
      bias (slope=0.85). The residual standard deviation (SD), an indicator of random
      variation, was +/-0.40g/kg. After BAC results were corrected for the time elapsed
      between sampling blood and breath, the y-intercept decreased to 0.10g/kg and
      0.004g/kg, respectively, when low (0.1g/kg/h) and high (0.25g/kg/h) rates of
      alcohol elimination were used. The proportional bias of 0.85 shows that the
      breath-alcohol test result reads lower than the actual BAC by 15% on average.
      This suggests that the BBR of 2260 used for calibration should be increased by
      about 15% to give closer agreement between BAC and BrAC. Because of the large
      random variation (SD+/-0.40g/kg), there is considerable uncertainty if and when
      results from the roadside screening test are used to estimate venous BAC. The
      roadside breath-alcohol screening instruments worked well for the purpose of
      selecting drivers above the statutory limit of 0.50g/kg. 

PMID- 24747669
TI  - Factors affecting accessibility to blowflies of bodies disposed in suitcases.
AB  - Criminals have been known to dispose of bodies in zipped suitcases in an attempt
      to conceal murder. In order to investigate the forensic implications of this mode
      of disposal on calculating time of death, it is necessary to study the
      accessibility of bodies in suitcases to blowflies (Diptera: Calliphoridae) and
      the possibility of oviposition and infestation under these circumstances. An
      experimental apparatus was designed that incorporated different zips (toothed and
      coil) of various gauges (4-6 mm) above a chicken liver bait. Gravid Calliphora
      vomitoria and Calliphora vicina females were attracted to and oviposited on and
      through these zips, both under laboratory and field conditions. Egg laying was
      significantly more frequent and with greater numbers of eggs when zips were in
      contact with the bait than when they were placed approximately 6cm above the
      bait. In the absence of bait, adult females could be stimulated to lay eggs on
      moistened zips, although the presence of blood accelerated egg laying compared to
      water alone. No eggs were laid on dry zips in the absence of bait. Of the first
      instar larvae tested, 89% were able to colonise the bait below the zips by
      passing through gaps between the teeth. Preliminary field studies using suitcases
      baited with a pig's head indicated that there was a delay of 1-3 days in
      oviposition when compared to laboratory conditions. This information has
      practical value in explaining the presence of larvae on enclosed bodies in
      suitcases and will help forensic entomologists estimate a more accurate minimum
      time since death. 

PMID- 24747670
TI  - Experimental investigation of the mechanical properties of brain simulants used
      for cranial gunshot simulation.
AB  - The mechanical properties of the human brain at high strain rate were
      investigated to analyse the mechanisms that cause backspatter when a cranial
      gunshot wound occurs. Different concentrations of gelatine and a new material
      (M1) developed in this work were tested and compared to bovine brain samples.
      Kinetic energy absorption and expansion rate of the samples caused by the impact
      of a bullet from .22 air rifle (AR) (average velocity (uav) of 290m/s) and .22
      long rifle (LR) (average velocity (uav) of 330m/s) were analysed using a high
      speed camera (24,000fps). The AR projectile had, in the region of interest, an
      average kinetic energy (Ek) of 42+/-1.3J. On average, the bovine brain absorbed
      50+/-5% of Ek, and the simulants 46-58+/-5%. The Ek of the .22 LR was 141+/-3.7J.
      The bovine brain absorbed 27% of the .22LR Ek and the simulants 15-29%. The
      expansion of the sample, after penetration, was measured. The bovine brain
      experienced significant plastic deformation whereas the gelatine solution
      exhibited a principally elastic response. The permanent damage patterns in the M1
      material were much closer to those in brain tissue, than were the damage patterns
      in the gelatine. The results provide a first step to developing a realistic
      experimental simulant for the human brain which can produce the same blood
      backspatter patterns as a human brain during a cranial gunshot. These results can
      also be used to improve the 3D models of human heads used in car crash and blast
      trauma injury research. 

PMID- 24747671
TI  - Recent non-chemical approaches to estimate the shooting distance.
AB  - Shooting distance estimation offers useful information for the reconstruction of
      firearm related incidents. The muzzle to target distance is usually estimated by
      examining the bullet entrance hole and the gunshot residue pattern. To visualize
      the pattern the forensic analyst usually uses presumptive tests based on color
      chemical reactions that are applied using long and tedious proceedings. Due to
      the drawbacks of the chemical tests recent developments for shooting distance
      estimation not based on color chemical tests were described in the literature.
      The present review covers the approaches for shooting distance estimation
      published in the last 10 years considering two types of target, clothing and
      skin. 

PMID- 24747672
TI  - Steam explosion of oilseed rape straw: establishing key determinants of
      saccharification efficiency.
AB  - Oilseed rape straw was steam exploded into hot water at a range of severities.
      The residues were fractionated into solid and liquid phases and chemically
      characterised. The effect of steam explosion on enzymatic hydrolysis of the water
      insoluble fractions was investigated by studying initial cellulase binding and
      hydrolysis yields for different cellulase doses. Time-course data was modelled to
      establish rate-dependent differences in saccharification as a function of
      pretreatment severity and associated chemical composition. The study concluded:
      (1) the initial hydrolysis rate was limited by the amount of (pectic) uronic acid
      remaining in the substrate; (2) the proportion of rapidly hydrolysable
      carbohydrate was most closely and positively related to lignin abundance and (3)
      the final sugar yield most closely related to xylan removal from the substrate.
      Comparisons between milled and un-milled steam exploded straw highlighted the
      influence that physical structure has on hydrolysis rates and yields,
      particularly at low severities. 

PMID- 24747673
TI  - Preparation and application of a novel bioflocculant by two strains of Rhizopus
      sp. using potato starch wastewater as nutrilite.
AB  - A complex bioflocculant MBF917 was prepared by Rhizopus sp. M9 and M17 using
      potato starch wastewater (PSW) as nutrilite, and its flocculation characteristics
      of treating PSW were studied. Culture conditions of the two strains were
      optimized, and flocculating conditions of the bioflocculant for treating PSW were
      also investigated. The optimal and economical culture conditions were determined
      as COD of about 1600 mg/L, 0.3 g/L urea and 0.04 g/L potassium dihydrogen
      phosphate, with no need of adding carbon sources or adjusting pH. When the
      bioflocculant was used to flocculate PSW, the optimal dosage was 0.1 mL/L with
      addition of 5 mL/L 10% CaCl2 as coagulant aid, and there was no need to adjust
      pH. After flocculation, COD and turbidity removal rates of the PSW could reach
      54.09% and 92.11%, respectively, and 1.1g/L proteic substance was recycled from
      the PSW as a byproduct that could be used for animal feed.

PMID- 24747674
TI  - Acidic processing of hemicellulosic saccharides from pine wood: product
      distribution and kinetic modeling.
AB  - Water soluble compounds were removed from Pinus pinaster wood by a mild aqueous
      extraction, and the treated wood was subjected to hydrothermal processing to
      convert most hemicelluloses into soluble saccharides (including low molecular
      weight polymers, oligomers and monosaccharides). The liquid phase containing
      hemicellulose-derived saccharides was acidified with sulfuric acid and heated up
      to 130-250 degrees C to obtain furans and levulinic acid as major products. The
      concentration profiles of the major compounds participating in the reactions were
      interpreted by a kinetic model. A maximum conversion of pentoses into furfural
      near 80% was predicted at high temperature and short time, conditions leading to
      24% conversion of hexoses into HMF. Production of levulinic acid was favored at
      low temperatures. Maximum molar conversion of hexoses into levulinic acid (66.7%
      at 130 degrees C) needed a long reaction time (235 h). A value of 53.0% can be
      achieved at 170 degrees C after 5 h.

PMID- 24747675
TI  - Synchrotron based infrared imaging and spectroscopy via focal plane array on live
      fibroblasts in D2O enriched medium.
AB  - We successfully tested the viability of using synchrotron-based full-field
      infrared imaging to study biochemical processes inside living cells. As a model
      system, we studied fibroblast cells exposed to a medium highly enriched with D2O.
      We could show that the experimental technique allows us to reproduce at the
      cellular level measurements that are normally performed on purified biological
      molecules. We can obtain information about lipid conformation and distribution,
      kinetics of hydrogen/deuterium exchange, and the formation of concentration
      gradients of H and O isotopes in water that are associated with cell metabolism.
      The implementation of the full field technique in a sequential imaging format
      gives a description of cellular biochemistry and biophysics that contains both
      spatial and temporal information. 

PMID- 24747676
TI  - Structural controllability and controlling centrality of temporal networks.
AB  - Temporal networks are such networks where nodes and interactions may appear and
      disappear at various time scales. With the evidence of ubiquity of temporal
      networks in our economy, nature and society, it's urgent and significant to focus
      on its structural controllability as well as the corresponding characteristics,
      which nowadays is still an untouched topic. We develop graphic tools to study the
      structural controllability as well as its characteristics, identifying the
      intrinsic mechanism of the ability of individuals in controlling a dynamic and
      large-scale temporal network. Classifying temporal trees of a temporal network
      into different types, we give (both upper and lower) analytical bounds of the
      controlling centrality, which are verified by numerical simulations of both
      artificial and empirical temporal networks. We find that the positive
      relationship between aggregated degree and controlling centrality as well as the
      scale-free distribution of node's controlling centrality are virtually
      independent of the time scale and types of datasets, meaning the inherent
      robustness and heterogeneity of the controlling centrality of nodes within
      temporal networks. 

PMID- 24747677
TI  - Activity of the mitochondrial pyruvate dehydrogenase complex in plants is
      stimulated in the presence of malate.
AB  - The effect of malate on the steady-state activity of the pea (Pisum sativum L.)
      and barley (Hordeum vulgare L.) leaf pyruvate dehydrogenase complex (PDC) has
      been studied in isolated mitochondria. The addition of malate was found to be
      stimulatory for the mitochondrial PDC, however there was no stimulation of
      chloroplast PDC. The stimulation was saturated below 1mM malate and was
      apparently related to a partially activated complex, which activity increased in
      the presence of malate by about twofold. Malate also reversed the reduction of
      PDC activity in the presence of glycine. Based on the obtained kinetic data, we
      suggest that the effect of malate is rather not a direct activation of PDC but
      involves the establishment of NAD-malate dehydrogenase equilibrium, decreasing
      concentration of NADH and relieving its inhibitory effect of PDC. 

PMID- 24747678
TI  - The transcription factor Zbtb32 controls the proliferative burst of virus
      specific natural killer cells responding to infection.
AB  - Natural killer (NK) cells are innate lymphocytes that exhibit many features of
      adaptive immunity, including clonal proliferation and long-lived memory. Here we
      demonstrate that the BTB-ZF transcription factor Zbtb32 (also known as ROG, FAZF,
      TZFP and PLZP) was essential for the proliferative burst and protective capacity
      of virus-specific NK cells. Signals from proinflammatory cytokines were both
      necessary and sufficient to induce high expression of Zbtb32 in NK cells. Zbtb32
      facilitated NK cell proliferation during infection by antagonizing the anti
      proliferative factor Blimp-1 (Prdm1). Our data support a model in which Zbtb32
      acts as a cellular 'hub' through which proinflammatory signals instruct a
      'proliferation-permissive' state in NK cells, thereby allowing their prolific
      expansion in response to viral infection. 

PMID- 24747679
TI  - Erlotinib or gefitinib as first-choice therapy for bronchorrhea in
      bronchioloalveolar carcinoma.

PMID- 24747680
TI  - Structural similarities in DNA packaging and delivery apparatuses in Herpesvirus
      and dsDNA bacteriophages.
AB  - Structural information can inform our understanding of virus origins and
      evolution. The herpesviruses and tailed bacteriophages constitute two large
      families of dsDNA viruses which infect vertebrates and prokaryotes respectively.
      A relationship between these disparate groups was initially suggested by
      similarities in their capsid assembly and DNA packaging strategies. This
      relationship has now been confirmed by a range of studies that have revealed
      common structural features in their capsid proteins, and similar organizations
      and sequence conservation in their DNA packaging machinery and maturational
      proteases. This concentration of conserved traits in proteins involved in
      essential and primordial capsid/packaging functions is evidence that these
      structures are derived from an ancient, common ancestor and is in sharp contrast
      to the lack of such evidence for other virus functions. 

PMID- 24747681
TI  - A comprehensive texture segmentation framework for segmentation of capillary non
      perfusion regions in fundus fluorescein angiograms.
AB  - Capillary non-perfusion (CNP) in the retina is a characteristic feature used in
      the management of a wide range of retinal diseases. There is no well-established
      computation tool for assessing the extent of CNP. We propose a novel texture
      segmentation framework to address this problem. This framework comprises three
      major steps: pre-processing, unsupervised total variation texture segmentation,
      and supervised segmentation. It employs a state-of-the-art multiphase total
      variation texture segmentation model which is enhanced by new kernel based region
      terms. The model can be applied to texture and intensity-based multiphase
      problems. A supervised segmentation step allows the framework to take expert
      knowledge into account, an AdaBoost classifier with weighted cost coefficient is
      chosen to tackle imbalanced data classification problems. To demonstrate its
      effectiveness, we applied this framework to 48 images from malarial retinopathy
      and 10 images from ischemic diabetic maculopathy. The performance of segmentation
      is satisfactory when compared to a reference standard of manual delineations:
      accuracy, sensitivity and specificity are 89.0%, 73.0%, and 90.8% respectively
      for the malarial retinopathy dataset and 80.8%, 70.6%, and 82.1% respectively for
      the diabetic maculopathy dataset. In terms of region-wise analysis, this method
      achieved an accuracy of 76.3% (45 out of 59 regions) for the malarial retinopathy
      dataset and 73.9% (17 out of 26 regions) for the diabetic maculopathy dataset.
      This comprehensive segmentation framework can quantify capillary non-perfusion in
      retinopathy from two distinct etiologies, and has the potential to be adopted for
      wider applications. 

PMID- 24747683
TI  - What tau distribution maximizes fast axonal transport toward the axonal synapse?
AB  - This theoretical research is aimed at investigating the question of why tau
      protein concentration exhibits a proximal-distal increase in healthy axons and a
      proximal-distal decrease in degenerating axons in Alzheimer's disease. We
      developed a model of fast axonal transport toward the axon synapse. The model is
      based on recently published experimental results by Dixit et al. (2008) [1] who
      reported that the attachment rate of kinesin-1 to MTs is reduced by tau.
      Cytoplasmic dynein is affected less by tau (dynein is affected at much higher tau
      concentrations than those that affect kinesin-1). We used the model to
      investigate the effect of various tau distributions along the axon length on
      organelle flux toward the axon synapse. We found that a proximal-distal increase
      in tau concentration leads to a higher organelle flux while a proximal-distal
      decrease in tau concentration leads to a smaller organelle flux than a uniform
      tau concentration. We also computed what tau distribution would give the largest
      organelle flux toward the synapse. We found that in order to maximize organelle
      flux, the tau concentration has to be at its minimum level in the proximal axon
      and its maximum level at the distal axon, which is in agreement with the bang
      bang principle in optimal control theory. 

PMID- 24747682
TI  - Impact of the loss of caveolin-1 on lung mass and cholesterol metabolism in mice
      with and without the lysosomal cholesterol transporter, Niemann-Pick type C1.
AB  - Caveolin-1 (Cav-1) is a major structural protein in caveolae in the plasma
      membranes of many cell types, particularly endothelial cells and adipocytes. Loss
      of Cav-1 function has been implicated in multiple diseases affecting the
      cardiopulmonary and central nervous systems, as well as in specific aspects of
      sterol and lipid metabolism in the liver and intestine. Lungs contain an
      exceptionally high level of Cav-1. Parameters of cholesterol metabolism in the
      lung were measured, initially in Cav-1-deficient mice (Cav-1(-/-)), and
      subsequently in Cav-1(-/-) mice that also lacked the lysosomal cholesterol
      transporter Niemann-Pick C1 (Npc1) (Cav-1(-/-):Npc1(-/-)). In 50-day-old Cav-1(-/
      ) mice fed a low- or high-cholesterol chow diet, the total cholesterol
      concentration (mg/g) in the lungs was marginally lower than in the Cav-1(+/+)
      controls, but due to an expansion in their lung mass exceeding 30%, whole-lung
      cholesterol content (mg/organ) was moderately elevated. Lung mass (g) in the Cav
      1(-/-):Npc1(-/-) mice (0.356+/-0.022) markedly exceeded that in their Cav
      1(+/+):Npc1(+/+) controls (0.137+/-0.009), as well as in their Cav-1(-/
      ):Npc1(+/+) (0.191+/-0.013) and Cav-1(+/+):Npc1(-/-) (0.213+/-0.022) littermates.
      The corresponding lung total cholesterol contents (mg/organ) in mice of these
      genotypes were 6.74+/-0.17, 0.71+/-0.05, 0.96+/-0.05 and 3.12+/-0.43,
      respectively, with the extra cholesterol in the Cav-1(-/-):Npc1(-/-) and Cav
      1(+/+):Npc1(-/-) mice being nearly all unesterified (UC). The exacerbation of the
      Npc1 lung phenotype and increase in the UC level in the Cav-1(-/-):Npc1(-/-) mice
      imply a regulatory role of Cav-1 in pulmonary cholesterol metabolism when
      lysosomal sterol transport is disrupted. 

PMID- 24747684
TI  - A novel behavioral strategy, continuous biased running, during chemotaxis in
      Drosophila larvae.
AB  - Animals collect and integrate information from their environment, and select an
      appropriate strategy to elicit a behavioral response. Here, we investigate the
      behavioral strategy employed by Drosophila larvae during chemotaxis toward a food
      source functioning as an attractive odor source. In larvae, sharp turns have been
      identified as the main strategy during locomotion to odorant sources, but the
      existence of runs orienting toward the direction of higher odor concentrations
      has not been described. In this study, we show the existence of such a successive
      orientation toward an odor source, which we term as biased running. Our
      behavioral analysis, which examines the relationship between larval rotational
      velocities and larval positions relative to an attractive odor source, brings out
      this newly found behavioral strategy. Additionally, theoretically estimated
      concentration gradients of chemoattractants between left and right olfactory
      organs were statistically correlated with rotational velocities during biased
      running. Finally, computer simulations demonstrated that biased running enhances
      navigation accuracy. Taken together, biased running is an effective behavioral
      strategy during chemotaxis, and this notion may provide a new insight on how
      animals can efficiently approach the odor source. 

PMID- 24747685
TI  - Descending effect on spinal nociception by amygdaloid glutamate varies with the
      submodality of noxious test stimulation.
AB  - Amygdala has an important role in the processing of primary emotions, such as
      fear. Additionally, amygdala is involved in processing and modulation of pain.
      While the amygdala, particularly its central nucleus (CeA), has been shown to
      contribute to pain control, the descending pain regulation by the CeA is still
      only partly characterized. Here heat and mechanical nociception was tested in
      both hind limbs of healthy rats with a chronic guide cannula for microinjection
      of glutamate into the CeA of the left or right hemisphere. The aim was to assess
      whether the descending pain regulatory effect by glutamate in the amygdala varies
      with the submodality or the body side of nociceptive testing, brain hemisphere or
      the amygdaloid glutamate receptor. Motor performance was assessed with the
      Rotarod test. Amygdaloid glutamate, independent of the treated hemisphere,
      produced a dose-related heat and mechanical antinociception that varied with the
      submodality of testing. Heat antinociception was short lasting (minutes),
      bilateral and not reversed by blocking the amygdaloid NMDA receptor with MK-801.
      In contrast, mechanical antinociception lasted longer (>20 min), was
      predominantly contralateral and reversed by blocking the amygdaloid NMDA
      receptor. At an antinociceptive dose, amygdaloid glutamate failed to influence
      motor performance. The results indicate that independent of the brain hemisphere,
      the spatial extent and duration of the descending antinociceptive effect induced
      by amygdaloid glutamate varies with the amygdaloid glutamate receptor and the
      submodality of pain.

PMID- 24747686
TI  - Possible effects of nitric oxide synthases on odor-induced behavioral changes in
      mice.
AB  - Although exposure to olfactory stimulants can induce neurobehavioral changes,
      there is a lack of data regarding specific effects on neurotransduction,
      especially nitric oxide (NO)-mediated neurotransduction. We investigated the
      relationship between altered behavioral performance and changes in the expression
      of nitric oxide synthase (NOS), nNOS, iNOS, and eNOS, in 2-methylbutyric (2MB)
      acid-exposed mice. Mice were exposed to 2MB acid by inhalation and olfactory
      preference/avoidance and motor coordination were measured. Additionally, we
      examined NOS expression in the olfactory bulb of the mouse brain. Mice exposed to
      2MB acid showed significant changes in olfactory preference and rotarod activity
      as compared with controls. Although there was no change in nNOS and iNOS
      expressions in the olfactory bulb of 2MB acid-exposed mice, eNOS expression
      increased significantly in the olfactory bulb of 9.0M 2MB acid-exposed mice.
      These data indicate that altered eNOS expression in the olfactory bulb may
      contribute to 2MB acid-induced behavioral changes. 

PMID- 24747687
TI  - Yulangsan polysaccharide attenuates withdrawal symptoms and regulates the NO
      pathway in morphine-dependent rats.
AB  - Yulangsan polysaccharide (YLSP) has been utilized as a phytomedicine to managing
      nervous dysfunction in China. Thus, this study aimed to evaluate the potential
      YLSP-mediated detoxification role against morphine dependence in rats. The
      results indicated that the morphine dependence model significantly increased
      withdrawal symptoms, levels of NO and NOS (P<0.05). Furthermore, monoaminergic
      neurotransmitters, including DA and NE, were detected at elevated levels in the
      ventral tegmental area (VTA), hippocampus (HIP) and prefrontal cortex (PFC),
      respectively, while the level of DA was decreased and NE was increased in the
      nucleus accumbens (NAc). Conversely, YLSP administration significantly reversed
      naloxone-induced withdrawal symptoms, expression of brain NO and NOS, and
      monoaminergic neurotransmitters (P<0.05). Interestingly, YLSP shows an even more
      effective trend in attenuating withdrawal symptoms than does clonidine, although
      without a significant difference. These findings indicate that YLSP attenuation
      of the naloxone-induced withdrawal symptoms of morphine dependence may be
      mediated by regulation of the NO pathway and modulation of monoaminergic
      neurotransmitters.

PMID- 24747688
TI  - Delayed treatments with pharmacological modulators of pre- and postsynaptic mGlu
      receptors rescue the hippocampus from kainate-induced neurodegeneration.
AB  - Gene expression of mGluR2, mGluR3 and mGluR5 was evaluated in the hippocampus and
      frontal cortex in Wistar rats in 1 and 4 weeks after bilateral microinjection of
      kainic acid into the dorsal hippocampus. The time-course of the receptors'
      expression suggested their adaptive role in response on the induction of
      excitotoxicity. It was assumed that the decrease of kainate-induced
      neurodegeneration could be achieved through simultaneous activation of
      presynaptic mGluRs and inhibition of mGlu postsynaptic receptors. Both negative
      allosteric modulator of mGluR5, MPEP, and agonist of mGluR2, LY354740, were
      administered intraperitoneally 5 days after microinjection of kainic acid. As
      shown by histochemical studies with cresyl violet and Fluoro-Jade, kainate
      induced significant damage of hippocampal neurons in the CA3 and CA1 fields.
      Pharmacological treatment with the negative modulator of mGlu5 receptors in
      common with the agonist of mGluR2 decreased kainate-induced neurodegeneration in
      dorsal hippocampus.

PMID- 24747689
TI  - Relationship between mitochondrial DNA copy number and SIRT1 expression in
      porcine oocytes.
AB  - The present study assessed the effect of resveratrol on the expression of SIRT1
      and mitochondrial quality and quantity in porcine oocytes. Supplementing the
      maturation medium with 20 uM resveratrol increased the expression of SIRT1, and
      enhanced mitochondrial functions, as observed from the increased ATP content and
      mitochondrial membrane potential. Addition of resveratrol also improved the
      ability of oocytes to develop into the blastocyst stage following activation. The
      effects of resveratrol on mitochondrial number were examined by comparing the
      mitochondrial DNA copy number (Mt number) between group of oocytes collected from
      the same donor gilt ovaries. Supplementing the maturation medium with only
      resveratrol did not affect the Mt number in the oocytes. However, supplementing
      the maturation medium with 10 uM MG132, a proteasome inhibitor, significantly
      increased the amount of ubiquitinated proteins and Mt number by 12 and 14%,
      respectively. In addition, when resveratrol was added to the medium containing
      MG132, the Mt number increased significantly by 39%, this effect was diminished
      by the addition of the SIRT1 inhibitor EX527. Furthermore, supplementing the
      medium with MG132 and EX527 did not affect Mt number. The mean SIRT1 expression
      in 20 oocytes was significantly and positively correlated with the Mt number in
      oocytes collected from the same donor. This study suggests that the expression of
      SIRT1 is associated with the Mt number in oocytes. In addition, activation of
      SIRT1 by resveratrol enhances the biosynthesis and degradation of mitochondria in
      oocytes, thereby replenishing and improving mitochondrial function and the
      developmental ability of oocytes. 

PMID- 24747691
TI  - Molecular monitoring of epithelial-to-mesenchymal transition in breast cancer
      cells by means of Raman spectroscopy.
AB  - In breast cancer the presence of cells undergoing the epithelial-to-mesenchymal
      transition is indicative of metastasis progression. Since metabolic features of
      breast tumour cells are critical in cancer progression and drug resistance, we
      hypothesized that the lipid content of malignant cells might be a useful indirect
      measure of cancer progression. In this study Multivariate Curve Resolution was
      applied to cellular Raman spectra to assess the metabolic composition of breast
      cancer cells undergoing the epithelial to mesenchymal transition. Multivariate
      Curve Resolution analysis led to the conclusion that this transition affects the
      lipid profile of cells, increasing tryptophan but maintaining a low fatty acid
      content in comparison with highly metastatic cells. Supporting those results, a
      Partial Least Square-Discriminant analysis was performed to test the ability of
      Raman spectroscopy to discriminate the initial steps of epithelial to mesenchymal
      transition in breast cancer cells. We achieved a high level of sensitivity and
      specificity, 94% and 100%, respectively. In conclusion, Raman microspectroscopy
      coupled with Multivariate Curve Resolution enables deconvolution and tracking of
      the molecular content of cancer cells during a biochemical process, being a
      powerful, rapid, reagent-free and non-invasive tool for identifying metabolic
      features of breast cancer cell aggressiveness at first stages of malignancy. 

PMID- 24747690
TI  - Cell migration to CXCL12 requires simultaneous IKKalpha and IKKbeta-dependent NF
      kappaB signaling.
AB  - CXCL12 and its unique receptor CXCR4, is critical for the homing of a variety of
      cell lineages during both development and tissue repair. CXCL12 is particularly
      important for the recruitment of hemato/lymphopoietic cells to their target
      organs. In conjunction with the damage-associated alarmin molecule HMGB1, CXCL12
      mediates immune effector and stem/progenitor cell migration towards damaged
      tissues for subsequent repair. Previously, we showed that cell migration to HMGB1
      simultaneously requires both IKKbeta and IKKalpha-dependent NF-kappaB activation.
      IKKbeta-mediated activation maintains sufficient expression of HMGB1's receptor
      RAGE, while IKKalpha-dependent NF-kappaB activation ensures continuous production
      of CXCL12, which complexes with HMGB1 to engage CXCR4. Here using fibroblasts and
      primary mature macrophages, we show that IKKbeta and IKKalpha are simultaneously
      essential for cell migration in response to CXCL12 alone. Non-canonical NF-kappaB
      pathway subunits RelB and p52 are also both essential for cell migration towards
      CXCL12, suggesting that IKKalpha is required to drive non-canonical NF-kappaB
      signaling. Flow cytometric analyses of CXCR4 expression show that IKKbeta, but
      not IKKalpha, is required to maintain a critical threshold level of this CXCL12
      receptor. Time-lapse video microscopy experiments in primary MEFs reveal that
      IKKalpha is required both for polarization of cells towards a CXCL12 gradient and
      to establish a basal level of velocity towards CXCL12. In addition, CXCL12
      modestly up-regulates IKKalpha-dependent p52 nuclear translocation and IKKalpha
      dependent expression of the CXCL12 gene. On the basis of our collective results
      we posit that IKKalpha is needed to maintain the basal expression of a critical
      protein co-factor required for cell migration to CXCL12. 

PMID- 24747692
TI  - Flotillin depletion affects ErbB protein levels in different human breast cancer
      cells.
AB  - The ErbB3 receptor is an important regulator of cell growth and carcinogenesis.
      Among breast cancer patients, up to 50-70% have ErbB3 overexpression and 20-30%
      show overexpressed or amplified ErbB2. ErbB3 has also been implicated in the
      development of resistance to several drugs used against cancers driven by ErbB1
      or ErbB2. One of the main challenges in ErbB-targeting therapy is to inactivate
      signaling mediated by ErbB2-ErbB3 oncogenic receptor complexes. We analyzed the
      regulatory role of flotillins on ErbB3 levels and ErbB2-ErbB3 complexes in SKBR3,
      MCF7 and MDA-MB-134-VI human breast cancer cells. Recently, we described a
      mechanism for interfering with ErbB2 signaling in breast cancer and demonstrated
      a molecular complex of flotillin scaffolding proteins with ErbB2 and Hsp90. In
      the present study, flotillins were found to be in a molecular complex with ErbB3,
      even in cells without the presence of ErbB2 or other ErbB receptors. Depletion of
      either flotillin-1 or flotillin-2 resulted in downregulation of ErbB3 and a
      selective reduction of ErbB2-ErbB3 receptor complexes. Moreover, flotillin-2
      depletion resulted in reduced activation of Akt and MAPK signaling cascades, and
      as a functional consequence of flotillin depletion, breast cancer cells showed an
      impaired cell migration. Altogether, we provide data demonstrating a novel and
      functional role of flotillins in the regulation of ErbB protein levels and
      stabilization of ErbB2-ErbB3 receptor complexes. Thus, flotillins are crucial
      regulators for oncogenic ErbB function and potential targets for cancer
      treatment. 

PMID- 24747693
TI  - The association of red cell distribution width and morbid obesity.

PMID- 24747694
TI  - Associations between infant feeding practice prior to six months and body mass
      index at six years of age.
AB  - Rapid growth during infancy is associated with increased risk of overweight and
      obesity and differences in weight gain are at least partly explained by means of
      infant feeding. The aim was to assess the associations between infant feeding
      practice in early infancy and body mass index (BMI) at 6 years of age. Icelandic
      infants (n = 154) were prospectively followed from birth to 12 months and again
      at age 6 years. Birth weight and length were gathered from maternity wards, and
      healthcare centers provided the measurements made during infancy up to 18 months
      of age. Information on breastfeeding practices was documented 0-12 months and a
      24-h dietary record was collected at 5 months. Changes in infant weight gain were
      calculated from birth to 18 months. Linear regression analyses were performed to
      examine associations between infant feeding practice at 5 months and body mass
      index (BMI) at 6 years. Infants who were formula-fed at 5 months of age grew
      faster, particularly between 2 and 6 months, compared to exclusively breastfed
      infants. At age 6 years, BMI was on average 1.1 kg/m2 (95% CI 0.2, 2.0) higher
      among infants who were formula fed and also receiving solid foods at 5 months of
      age compared to those exclusively breastfed. In a high-income country such as
      Iceland, early introduction of solid foods seems to further increase the risk of
      high childhood BMI among formula fed infants compared with exclusively breastfed
      infants, although further studies with greater power are needed. 

PMID- 24747695
TI  - Endotracheal intubation in mice via direct laryngoscopy using an otoscope.
AB  - Mice, both wildtype and transgenic, are the principal mammalian model in
      biomedical research currently. Intubation and mechanical ventilation are
      necessary for whole animal experiments that require surgery under deep anesthesia
      or measurements of lung function. Tracheostomy has been the standard for
      intubating the airway in these mice to allow mechanical ventilation. Orotracheal
      intubation has been reported but has not been successfully used in many studies
      because of the substantial technical difficulty or a requirement for highly
      specialized and expensive equipment. Here we report a technique of direct
      laryngoscopy using an otoscope fitted with a 2.0 mm speculum and using a 20 G
      intravenous catheter as an endotracheal tube. We have used this technique
      extensively and reliably to intubate and conduct accurate assessments of lung
      function in mice. This technique has proven safe, with essentially no animal loss
      in experienced hands. Moreover, this technique can be used for repeated studies
      of mice in chronic models. 

PMID- 24747696
TI  - Predictive genomics: a cancer hallmark network framework for predicting tumor
      clinical phenotypes using genome sequencing data.
AB  - Tumor genome sequencing leads to documenting thousands of DNA mutations and other
      genomic alterations. At present, these data cannot be analyzed adequately to aid
      in the understanding of tumorigenesis and its evolution. Moreover, we have little
      insight into how to use these data to predict clinical phenotypes and tumor
      progression to better design patient treatment. To meet these challenges, we
      discuss a cancer hallmark network framework for modeling genome sequencing data
      to predict cancer clonal evolution and associated clinical phenotypes. The
      framework includes: (1) cancer hallmarks that can be represented by a few
      molecular/signaling networks. 'Network operational signatures' which represent
      gene regulatory logics/strengths enable to quantify state transitions and
      measures of hallmark traits. Thus, sets of genomic alterations which are
      associated with network operational signatures could be linked to the
      state/measure of hallmark traits. The network operational signature transforms
      genotypic data (i.e., genomic alterations) to regulatory phenotypic profiles
      (i.e., regulatory logics/strengths), to cellular phenotypic profiles (i.e.,
      hallmark traits) which lead to clinical phenotypic profiles (i.e., a collection
      of hallmark traits). Furthermore, the framework considers regulatory logics of
      the hallmark networks under tumor evolutionary dynamics and therefore also
      includes: (2) a self-promoting positive feedback loop that is dominated by a
      genomic instability network and a cell survival/proliferation network is the main
      driver of tumor clonal evolution. Surrounding tumor stroma and its host immune
      systems shape the evolutionary paths; (3) cell motility initiating metastasis is
      a byproduct of the above self-promoting loop activity during tumorigenesis; (4)
      an emerging hallmark network which triggers genome duplication dominates a feed
      forward loop which in turn could act as a rate-limiting step for tumor formation;
      (5) mutations and other genomic alterations have specific patterns and tissue
      specificity, which are driven by aging and other cancer-inducing agents. This
      framework represents the logics of complex cancer biology as a myriad of
      phenotypic complexities governed by a limited set of underlying organizing
      principles. It therefore adds to our understanding of tumor evolution and
      tumorigenesis, and moreover, potential usefulness of predicting tumors'
      evolutionary paths and clinical phenotypes. Strategies of using this framework in
      conjunction with genome sequencing data in an attempt to predict personalized
      drug targets, drug resistance, and metastasis for cancer patients, as well as
      cancer risks for healthy individuals are discussed. Accurate prediction of cancer
      clonal evolution and clinical phenotypes will have substantial impact on timely
      diagnosis, personalized treatment and personalized prevention of cancer. 

PMID- 24747697
TI  - Modeling metabolism: a window toward a comprehensive interpretation of networks
      in cancer.
AB  - Given the multi-factorial nature of cancer, uncovering its metabolic alterations
      and evaluating their implications is a major challenge in biomedical sciences
      that will help in the optimal design of personalized treatments. The advance of
      high-throughput technologies opens an invaluable opportunity to monitor the
      activity at diverse biological levels and elucidate how cancer originates,
      evolves and responds under drug treatments. To this end, researchers are
      confronted with two fundamental questions: how to interpret high-throughput data
      and how this information can contribute to the development of personalized
      treatment in patients. A variety of schemes in systems biology have been
      suggested to characterize the phenotypic states associated with cancer by
      utilizing computational modeling and high-throughput data. These theoretical
      schemes are distinguished by the level of complexity of the biological mechanisms
      that they represent and by the computational approaches used to simulate them.
      Notably, these theoretical approaches have provided a proper framework to explore
      some distinctive metabolic mechanisms observed in cancer cells such as the
      Warburg effect. In this review, we focus on presenting a general view of some of
      these approaches whose application and integration will be crucial in the
      transition from local to global conclusions in cancer studies. We are convinced
      that multidisciplinary approaches are required to construct the bases of an
      integrative and personalized medicine, which has been and remains a fundamental
      task in the medicine of this century. 

PMID- 24747698
TI  - Stable copper-zeolite filter media for bacteria removal in stormwater.
AB  - Cu(2+)-exchanged zeolite (ZCu) as antibacterial media shows great potential for
      bacteria removal from stormwater, but its stability in high salinity water needs
      attention. In this study, stable antibacterial media were developed by modifying
      ZCu through calcination and in situ Cu(OH)2 coating. Their stability and
      Escherichia coli removal efficiency along with impact of salinity were examined
      in gravity-fed columns. While copper leaching from ZCu was 20mg/L in test water
      of salinity 250MUS/cm, it was reduced by over 97% through Cu(OH)2 coating and/or
      calcination. ZCu coated with Cu(OH)2 followed by heat treatment at 180 degrees C
      (ZCuCuO180) exhibited more consistent E. coli removal (1.7-2.7 log) than ZCu (1.2
      3.3 log) in test water of varied salinity but constant contact time 22min. ZCu
      calcined at 400 degrees C (ZCu400) effectively inactivated removed bacteria
      during 24h drying period. In the presence of native microbial communities, new
      sand filters, particularly those having ZCu400 at the top to inactivate bacteria
      during drying periods and ZCuCuO180 midway to capture and inactivate microbes
      during wet events, provided the best bacterial removal (1.7 log, contact time
      9min). Copper leaching from this design was 9MUg/L, well below long-term
      irrigation standard of 200MUg/L. 

PMID- 24747699
TI  - Extracellular wire tetrode recording in brain of freely walking insects.
AB  - Increasing interest in the role of brain activity in insect motor control
      requires that we be able to monitor neural activity while insects perform natural
      behavior. We previously developed a technique for implanting tetrode wires into
      the central complex of cockroach brains that allowed us to record activity from
      multiple neurons simultaneously while a tethered cockroach turned or altered
      walking speed. While a major advance, tethered preparations provide access to
      limited behaviors and often lack feedback processes that occur in freely moving
      animals. We now present a modified version of that technique that allows us to
      record from the central complex of freely moving cockroaches as they walk in an
      arena and deal with barriers by turning, climbing or tunneling. Coupled with high
      speed video and cluster cutting, we can now relate brain activity to various
      parameters of the movement of freely behaving insects.

PMID- 24747700
TI  - Common variable immunodeficiency and autoimmunity--an inconvenient truth.
AB  - Coexisting morbidities in CVID include bronchiectasis, autoimmunity and
      malignancies. The incidence of autoimmune disease in CVID patients may approach
      20% of cases. The most common autoimmune disease found in CVID patients is
      autoimmune cytopenia, but rheumatoid arthritis, lupus, and now primary biliary
      cirrhosis have also been reported. The coexistence of immunodeficiency and
      autoimmunity appears paradoxical, since one represents a hypoimmune state and the
      other a hyperimmune state. However, this paradox may not actually be all that
      implausible due to the complex nature of immune cells, signaling pathways and
      their interactions. The cellular alterations in combined variable
      immunodeficiency include a range of T and B cell abnormalities. Selective immune
      derangements found in CVID include a downregulation of regulatory T cells (Treg
      cells), accelerated T cell apoptosis, abnormal cytokine production secondary to
      cytokine gene polymorphisms and increased autoreactive B cell production. The
      impact of these abnormalities on T and B cell interaction may not only explain
      the immunodeficiency but also the development of autoimmunity in select groups of
      patients with CVID. The variability in the clinical manifestations of CVID as a
      result of this immune interaction suggests that CVID is not one disease but many.
      This is important because it follows that the treatment of CVID may not always be
      the same, but may need to be directed specifically towards each individual
      patient. 

PMID- 24747701
TI  - Vaccines against tropical parasitic diseases: a persisting answer to a persisting
      problem.

PMID- 24747702
TI  - TACTILE becomes tangible: CD96 discloses its inhibitory peculiarities.

PMID- 24747703
TI  - New inhibitory signaling by CTLA-4.

PMID- 24747704
TI  - Countering inflammatory signals in obesity.

PMID- 24747705
TI  - SGK1: master and commander of the fate of helper T cells.

PMID- 24747712
TI  - The enemy within: endogenous retroelements and autoimmune disease.
AB  - Inappropriate or chronic detection of self nucleic acids by the innate immune
      system underlies many human autoimmune diseases. We discuss here an unexpected
      source of endogenous immunostimulatory nucleic acids: the reverse-transcribed
      cDNA of endogenous retroelements. The interplay between innate immune sensing and
      clearance of retroelement cDNA has important implications for the understanding
      of immune responses to infectious retroviruses such as human immunodeficiency
      virus (HIV). Furthermore, the detection of cDNA by the innate immune system
      reveals an evolutionary tradeoff: selection for a vigorous, sensitive response to
      infectious retroviruses may predispose the inappropriate detection of endogenous
      retroelements. We propose that this tradeoff has placed unique constraints on the
      sensitivity of the DNA-activated antiviral response, with implications for the
      interactions of DNA viruses and retroviruses with their hosts. Finally, we
      discuss how better understanding of the intersection of retroelement biology and
      innate immunity can guide the way to novel therapies for specific autoimmune
      diseases. 

PMID- 24747713
TI  - Critical perspectives on successful aging: does it "appeal more than it
      illuminates"?
AB  - "Successful aging" is one of gerontology's most successful ideas. Applied as a
      model, a concept, an approach, an experience, and an outcome, it has inspired
      researchers to create affiliated terms such as "healthy," "positive," "active,"
      "productive," and "effective" aging. Although embraced as an optimistic approach
      to measuring life satisfaction and as a challenge to ageist traditions based on
      decline, successful aging as defined by John Rowe and Robert Kahn has also
      invited considerable critical responses. This article takes a critical
      gerontological perspective to explore such responses to the Rowe-Kahn successful
      aging paradigm by summarizing its empirical and methodological limitations,
      theoretical assumptions around ideas of individual choice and lifestyle, and
      inattention to intersecting issues of social inequality, health disparities, and
      age relations. The latter point is elaborated with an examination of income,
      gender, racial, ethnic, and age differences in the United States. Conclusions
      raise questions of social exclusion and the future of successful aging research. 

PMID- 24747714
TI  - Characterisation of mixing in the proximal duodenum of the rat during
      longitudinal contractions and comparison with a fluid mechanical model based on
      spatiotemporal motility data.
AB  - The understanding of mixing and mass transfers of nutrients and drugs in the
      small intestine is of prime importance in creating formulations that manipulate
      absorption and digestibility. We characterised mixing using a dye tracer
      methodology during spontaneous longitudinal contractions, i.e. pendular activity,
      in 10 cm segments of living proximal duodenum of the rat maintained ex-vivo. The
      residence time distribution (RTD) of the tracer was equivalent to that generated
      by a small number (8) of continuous stirred tank reactors in series. Fluid
      mechanical modelling, that was based on real sequences of longitudinal
      contractions, predicted that dispersion should occur mainly in the periphery of
      the lumen. Comparison with the experimental RTD showed that centriluminal
      dispersion was accurately simulated whilst peripheral dispersion was
      underestimated. The results therefore highlighted the potential importance of
      micro-phenomena such as microfolding of the intestinal mucosa in peripheral
      mixing. We conclude that macro-scale modeling of intestinal flow is useful in
      simulating centriluminal mixing, whereas multi-scales strategies must be
      developed to accurately model mixing and mass transfers at the periphery of the
      lumen. 

PMID- 24747715
TI  - Characterization of dietary patterns in the Danish national birth cohort in
      relation to preterm birth.
AB  - BACKGROUND: Dietary patterns better reflect eating habits as opposed to single
      dietary components. However, the use of dietary pattern analysis in nutritional
      epidemiology has been hampered by the complexity of interpreting and presenting
      multidimensional dietary data. METHODS: This study extracts and visualizes
      dietary patterns from self-reported dietary data collected in mid-pregnancy (25th
      week of gestation) from nearly 60,000 mother-child pairs part of a prospective,
      longitudinal cohort (Danish National Birth Cohort) and further examines their
      associations with spontaneous and induced preterm birth (gestational age<259 days
      (<37 weeks)). RESULTS: A total of seven dietary patterns were extracted by
      principal component analysis, characterized and visualized by color-coded spider
      plots, and referred to as: Vegetables/Prudent, Alcohol, Western, Nordic, Seafood,
      Candy and Rice/Pasta/Poultry. A consistent dose-response association with preterm
      birth was only observed for Western diet with an odds ratio of 1.30 (95% CI:
      1.13, 1.49) comparing the highest to the lowest quintile. This association was
      primarily driven by induced preterm deliveries (odds ratio = 1.66, 95% CI: 1.30,
      2.11, comparing the highest to the lowest quintile) while the corresponding odds
      ratio for spontaneous preterm deliveries was more modest (odds ratio = 1.18, 95%
      CI: 0.99, 1.39). All based on adjusted analyses. CONCLUSIONS: In conclusion, this
      study presented a simple and novel framework for visualizing correlation
      structures between overall consumption of foods group and their relation to
      nutrient intake and maternal characteristics. Our results suggest that Western
      type diet, high in meat and fats and low in fruits and vegetables, is associated
      with increased odds of induced preterm birth.

PMID- 24747716
TI  - Identification of Bacillus species occurring in Kantong, an acid fermented seed
      condiment produced in Ghana.
AB  - Kantong is a condiment produced in Ghana by the spontaneous fermentation of kapok
      tree (Ceiba pentandra) seeds with cassava flour as an additive. Fermentation is
      over a 48h period followed by a drying and a kneading process. Although lactic
      acid bacteria (LAB) have previously been identified other micro-organisms may
      also be involved in the fermentation process. In this study we examined the
      occurrence of aerobic endospore-forming bacteria (AEB) in raw materials, during
      fermentation and in the final product at 2 production sites in Northern Ghana.
      Total aerobic mesophilic bacterial counts increased from 5.4+/-0.1log10CFU/g in
      the raw materials to 8.9+/-0.1log10CFU/g in the final products, with the AEB
      accounting for between 23% and 80% of the total aerobic mesophilic (TAM) counts.
      A total of 196 AEB were identified at a species/subspecies level by the use of
      phenotypic tests and genotypic methods including M13-PCR typing, 16S rRNA and
      gyrA gene sequencing. Bacillus subtilis subsp. subtilis (63% of the AEB),
      Bacillus safensis (26% of the AEB) and Bacillus amyloliquefaciens subsp.
      plantarum/Bacillus methylotrophicus (9% of the AEB) were the predominant Bacillus
      species during fermentation and in the final products. B. amyloliquefaciens/B.
      methylotrophicus originated from cassava flour, B. safensis from seeds and
      cassava flour, while the origin of B. subtilis was less clear. Brevibacillus agri
      and Peanibacillus spp. occurred sporadically. Further investigations are required
      to elucidate the role of AEB occurring in high numbers, in the fermentation of
      Kantong. 

PMID- 24747717
TI  - Genome-wide comparative analysis of 20 miniature inverted-repeat transposable
      element families in Brassica rapa and B. oleracea.
AB  - Miniature inverted-repeat transposable elements (MITEs) are ubiquitous, non
      autonomous class II transposable elements. Here, we conducted genome-wide
      comparative analysis of 20 MITE families in B. rapa, B. oleracea, and Arabidopsis
      thaliana. A total of 5894 and 6026 MITE members belonging to the 20 families were
      found in the whole genome pseudo-chromosome sequences of B. rapa and B. oleracea,
      respectively. Meanwhile, only four of the 20 families, comprising 573 members,
      were identified in the Arabidopsis genome, indicating that most of the families
      were activated in the Brassica genus after divergence from Arabidopsis. Copy
      numbers varied from 4 to 1459 for each MITE family, and there was up to 6-fold
      variation between B. rapa and B. oleracea. In particular, analysis of intact
      members showed that whereas eleven families were present in similar copy numbers
      in B. rapa and B. oleracea, nine families showed copy number variation ranging
      from 2- to 16-fold. Four of those families (BraSto-3, BraTo-3, 4, 5) were more
      abundant in B. rapa, and the other five (BraSto-1, BraSto-4, BraTo-1, 7 and
      BraHAT-1) were more abundant in B. oleracea. Overall, 54% and 51% of the MITEs
      resided in or within 2 kb of a gene in the B. rapa and B. oleracea genomes,
      respectively. Notably, 92 MITEs were found within the CDS of annotated genes,
      suggesting that MITEs might play roles in diversification of genes in the
      recently triplicated Brassica genome. MITE insertion polymorphism (MIP) analysis
      of 289 MITE members showed that 52% and 23% were polymorphic at the inter- and
      intra-species levels, respectively, indicating that there has been recent MITE
      activity in the Brassica genome. These recently activated MITE families with
      abundant MIP will provide useful resources for molecular breeding and
      identification of novel functional genes arising from MITE insertion. 

PMID- 24747718
TI  - Polyomavirus miRNAs: the beginning.
AB  - Polyomaviruses are small, double stranded DNA viruses that replicate in the
      nucleus of the infected cell. Since 2005, clear evidence for miRNAs has been
      presented for a subset of the members of this viral family, each of which express
      a single miRNA. All the miRNAs share in common the ability to regulate expression
      of the major viral regulatory protein, large T antigen. Growing evidence suggests
      that the major role of the miRNA is to control viral replication. In vitro
      studies suggesting an immmunomodulatory role for the miRNA have not been
      supported by in vivo infections. Very little is known about cellular targets of
      the viral miRNAs, however. Thus, much remains to be learned about these
      interesting non-coding RNAs. 

PMID- 24747719
TI  - Mechanism of an indirect effect of aqueous cigarette smoke extract on the
      adhesion of monocytic cells to endothelial cells in an in vitro assay revealed by
      transcriptomics analysis.
AB  - The adhesion of monocytic cells to the "dysfunctional" endothelium constitutes a
      critical step in the initiation of atherosclerosis. Cigarette smoke (CS) has been
      shown to contribute to this process, the complex mechanism of which still needs
      to be unraveled. We developed an in vitro adhesion assay to investigate the CS
      induced adhesion of monocytic MM6 cells to human umbilical vein endothelial cells
      (HUVECs) following exposure to an aqueous CS extract (smoke-bubbled phosphate
      buffered saline: sbPBS), reasoning that in vivo monocytes and endothelial cells
      are exposed primarily to soluble constituents from inhaled CS absorbed through
      the lung alveolar wall. MM6 cell adhesion was increased exclusively by the
      conditioned medium from sbPBS-exposed MM6 cells, not by direct sbPBS exposure of
      the HUVECs within a range of sbPBS doses. Using a transcriptomics approach
      followed by confirmation experiments, we identified different exposure effects on
      both cell types and a key mechanism by which sbPBS promoted the adhesion of MM6
      cells to HUVECs. While sbPBS provoked a strong oxidative stress response in both
      cell types, the expression of E-selectin, VCAM-1 and ICAM-1, responsible for the
      adhesion of MM6 cells to HUVECs, was induced in the latter through a
      proinflammatory paracrine effect. We confirmed that this effect was driven mainly
      by TNFalpha produced by MM6 cells exposed to sbPBS. In conclusion, we have
      elucidated an indirect mechanism by which sbPBS increases the adhesion of
      monocytic cells to endothelial cells in this in vitro assay that was designed for
      tobacco product risk assessment while mimicking the in vivo exposure conditions
      as closely as possible. 

PMID- 24747720
TI  - Adverse effect of cake collapse on the functional integrity of freeze-dried bull
      spermatozoa.
AB  - Under optimal freeze-drying conditions, solutions exhibit a cake-like porous
      structure. However, if the solution temperature is higher than the glass
      transition temperature of the maximally freeze-concentrated phase (Tg') during
      drying phase, the glassy matrix undergoes viscous flow, resulting in cake
      collapse. The purpose of the present study was to investigate the effect of cake
      collapse on the integrity of freeze-dried bull spermatozoa. In a preliminary
      experiment, factors affecting the Tg' of conventional EGTA buffer (consisting of
      Tris-HCl, EGTA and NaCl) were investigated in order to establish the main
      experimental protocol because EGTA buffer Tg' was too low (-45.0 degrees C) to
      suppress collapse. Modification of the EGTA buffer composition by complete
      removal of NaCl and addition of trehalose (mEGTA buffer) resulted in an increase
      of Tg' up to -27.7 degrees C. In the main experiment, blastocyst yields after
      ooplasmic injection of freeze-dried sperm preserved in collapsed cakes (drying
      temperature: 0 or -15 degrees C) were significantly lower than those of sperm
      preserved in non-collapsed cake (drying temperature: -30 degrees C). In
      conclusion, freeze-dried cake collapse may be undesirable for maintaining sperm
      functions to support embryonic development, and can be inhibited by controlling
      both Tg' of freeze-drying buffer and temperature during the drying phase.

PMID- 24747721
TI  - Classification of fricative consonants for speech enhancement in hearing devices.
AB  - OBJECTIVE: To investigate a set of acoustic features and classification methods
      for the classification of three groups of fricative consonants differing in place
      of articulation. METHOD: A support vector machine (SVM) algorithm was used to
      classify the fricatives extracted from the TIMIT database in quiet and also in
      speech babble noise at various signal-to-noise ratios (SNRs). Spectral features
      including four spectral moments, peak, slope, Mel-frequency cepstral coefficients
      (MFCC), Gammatone filters outputs, and magnitudes of fast Fourier Transform (FFT)
      spectrum were used for the classification. The analysis frame was restricted to
      only 8 msec. In addition, commonly-used linear and nonlinear principal component
      analysis dimensionality reduction techniques that project a high-dimensional
      feature vector onto a lower dimensional space were examined. RESULTS: With 13
      MFCC coefficients, 14 or 24 Gammatone filter outputs, classification performance
      was greater than or equal to 85% in quiet and at +10 dB SNR. Using 14 Gammatone
      filter outputs above 1 kHz, classification accuracy remained high (greater than
      80%) for a wide range of SNRs from +20 to +5 dB SNR. CONCLUSIONS: High levels of
      classification accuracy for fricative consonants in quiet and in noise could be
      achieved using only spectral features extracted from a short time window. Results
      of this work have a direct impact on the development of speech enhancement
      algorithms for hearing devices.

PMID- 24747722
TI  - Isolation, culture, and transplantation of muscle satellite cells.
AB  - Muscle satellite cells are a stem cell population required for postnatal skeletal
      muscle development and regeneration, accounting for 2-5% of sublaminal nuclei in
      muscle fibers. In adult muscle, satellite cells are normally mitotically
      quiescent. Following injury, however, satellite cells initiate cellular
      proliferation to produce myoblasts, their progenies, to mediate the regeneration
      of muscle. Transplantation of satellite cell-derived myoblasts has been widely
      studied as a possible therapy for several regenerative diseases including
      muscular dystrophy, heart failure, and urological dysfunction. Myoblast
      transplantation into dystrophic skeletal muscle, infarcted heart, and
      dysfunctioning urinary ducts has shown that engrafted myoblasts can differentiate
      into muscle fibers in the host tissues and display partial functional improvement
      in these diseases. Therefore, the development of efficient purification methods
      of quiescent satellite cells from skeletal muscle, as well as the establishment
      of satellite cell-derived myoblast cultures and transplantation methods for
      myoblasts, are essential for understanding the molecular mechanisms behind
      satellite cell self-renewal, activation, and differentiation. Additionally, the
      development of cell-based therapies for muscular dystrophy and other regenerative
      diseases are also dependent upon these factors. However, current prospective
      purification methods of quiescent satellite cells require the use of expensive
      fluorescence-activated cell sorting (FACS) machines. Here, we present a new
      method for the rapid, economical, and reliable purification of quiescent
      satellite cells from adult mouse skeletal muscle by enzymatic dissociation
      followed by magnetic-activated cell sorting (MACS). Following isolation of pure
      quiescent satellite cells, these cells can be cultured to obtain large numbers of
      myoblasts after several passages. These freshly isolated quiescent satellite
      cells or ex vivo expanded myoblasts can be transplanted into cardiotoxin (CTX)
      induced regenerating mouse skeletal muscle to examine the contribution of donor
      derived cells to regenerating muscle fibers, as well as to satellite cell
      compartments for the examination of self-renewal activities. 

PMID- 24747723
TI  - Radiologic and clinical bronchiectasis associated with autosomal dominant
      polycystic kidney disease.
AB  - BACKGROUND: Polycystin 1 and 2, the protein abnormalities associated with
      autosomal dominant polycystic kidney disease (ADPKD), are also found in airway
      cilia and smooth muscle cells. There is evidence of increased radiologic
      bronchiectasis associated with ADPKD, though the clinical and functional
      implications of this association are unknown. We hypothesized an increased
      prevalence of both radiologic and clinical bronchiectasis is associated with
      APDKD as compared to non-ADPKD chronic kidney disease (CKD) controls. MATERIALS
      AND METHODS: A retrospective case-control study was performed at our institution
      involving consecutive ADPKD and non-ADPKD chronic kidney disease (CKD) patients
      seen over a 13 year period with both chest CT and PFT. CTs were independently
      reviewed by two blinded thoracic radiologists. Manually collected clinical data
      included symptoms, smoker status, transplant history, and PFT findings. RESULTS:
      Ninety-two ADPKD and 95 non-ADPKD CKD control patients were compared. Increased
      prevalence of radiologic bronchiectasis, predominantly mild lower lobe disease,
      was found in ADPKD patients compared to CKD control (19 vs. 9%, P = 0.032, OR
      2.49 (CI 1.1-5.8)). After adjustment for covariates, ADPKD was associated with
      increased risk of radiologic bronchiectasis (OR 2.78 (CI 1.16-7.12)). Symptomatic
      bronchiectasis occurred in approximately a third of ADPKD patients with
      radiologic disease. Smoking was associated with increased radiologic
      bronchiectasis in ADPKD patients (OR 3.59, CI 1.23-12.1). CONCLUSIONS:
      Radiological bronchiectasis is increased in patients with ADPKD particularly
      those with smoking history as compared to non-ADPKD CKD controls. A third of such
      patients have symptomatic disease. Bronchiectasis should be considered in the
      differential in ADPKD patients with respiratory symptoms and smoking history.

PMID- 24747724
TI  - Influence of crop load on the expression patterns of starch metabolism genes in
      alternate-bearing citrus trees.
AB  - The fruit is the main sink organ in Citrus and captures almost all available
      photoassimilates during its development. Consequently, carbohydrate partitioning
      and starch content depend on the crop load of Citrus trees. Nevertheless, little
      is known about the mechanisms controlling the starch metabolism at the tree level
      in relation to presence of fruit. The aim of this study was to find the relation
      between the seasonal variation of expression and activity of the genes involved
      in carbon metabolism and the partition and allocation of carbohydrates in
      'Salustiana' sweet orange trees with different crop loads. Metabolisable
      carbohydrates, and the expression and activity of the enzymes involved in sucrose
      and starch metabolism, including sucrose transport, were determined during the
      year in the roots and leaves of 40-year-old trees bearing heavy crop loads ('on'
      trees) and trees with almost no fruits ('off' trees). Fruit altered
      photoassimilate partitioning in trees. Sucrose content tended to be constant in
      roots and leaves, and surplus fixed carbon is channeled to starch production.
      Differences between 'on' and 'off' trees in starch content can be explained by
      differences in ADP-glucose pyrophosphorylase (AGPP) expression/activity and alpha
      amylase activity which varies depending on crop load. The observed relation of
      AGPP and UGPP (UDP-glucose pyrophosphorylase) is noteworthy and indicates a
      direct link between sucrose and starch synthesis. Furthermore, different roles
      for sucrose transporter SUT1 and SUT2 have been proposed. Variation in soluble
      sugars content cannot explain the differences in gene expression between the 'on'
      and 'off' trees. A still unknown signal from fruit should be responsible for this
      control.

PMID- 24747726
TI  - The comparative morphology of epidermal glands in Pentatomoidea (Heteroptera).
AB  - The Heteroptera show a diversity of glands associated with the epidermis. They
      have multiple roles including the production of noxious scents. Here, we examine
      the cellular arrangement and cytoskeletal components of the scent glands of
      pentatomoid Heteroptera in three families, Pentatomidae (stink bugs),
      Tessaratomidae, and Scutelleridae (shield-backed bugs or jewel bugs). The glands
      are; (1) the dorsal abdominal glands, (2) the tubular glands of the composite
      metathoracic gland, and (3) the accessory gland component of the composite
      metathoracic gland. The dorsal abdominal glands are at their largest in nymphs
      and decrease in size in adults. The metathoracic gland is an adult-specific gland
      unit with a reservoir and multiple types of gland cells. The accessory gland is
      composed of many unicellular glands concentrated in a sinuous line across the
      reservoir wall. The lateral tubular gland is composed of two-cell units. The
      dorsal abdominal glands of nymphs are composed of three-cell units with a
      prominent cuticular component derived from the saccule cell sitting between the
      duct and receiving canal. The cuticular components that channel secretion from
      the microvilli of the secretory cell to the exterior differ in the three gland
      types. The significance of the numbers of cells comprising gland units is related
      to the role of cells in regenerating the cuticular components of the glands at
      moulting in nymphs.

PMID- 24747725
TI  - Proliferation potential of Muller glia after retinal damage varies between mouse
      strains.
AB  - Retinal Muller glia can serve as a source for regeneration of damaged retinal
      neurons in fish, birds and mammals. However, the proliferation rate of Muller
      glia has been reported to be low in the mammalian retina. To overcome this
      problem, growth factors and morphogens have been studied as potent promoters of
      Muller glial proliferation, but the molecular mechanisms that limit the
      proliferation of Muller glia in the mammalian retina remain unknown. In the
      present study, we found that the degree of damage-induced Muller glia
      proliferation varies across mouse strains. In mouse line 129*1/SvJ (129), there
      was a significantly larger proliferative response compared with that observed in
      C57BL/6 (B6) after photoreceptor cell death. Treatment with a Glycogen synthase
      kinase 3 (GSK3) inhibitor enhanced the proliferation of Muller glia in 129 but
      not in B6 mouse retinas. We therefore focused on the different gene expression
      patterns during retinal degeneration between B6 and 129. Expression levels of
      Cyclin D1 and Nestin correlated with the degree of Muller glial proliferation. A
      comparison of genome-wide gene expression between B6 and 129 showed that distinct
      sets of genes were upregulated in the retinas after damage, including immune
      response genes and chromatin remodeling factors. 

PMID- 24747727
TI  - Reduced respiratory sinus arrhythmia in adults born at extremely low birth
      weight: evidence of premature parasympathetic decline?
AB  - Individuals born at extremely low birth weight (ELBW; <1000 g) are exposed to
      early adversity in multiple forms. Given that substantial development of the
      autonomic nervous system (ANS) occurs during the third trimester of gestation,
      ANS functioning may be altered in adults who were born before reaching 28 weeks
      of gestational age. The aims of the study were to: (1) determine whether two
      indices of ANS functioning [resting heart period (HP) and respiratory sinus
      arrhythmia (RSA)], differed between adult ELBW survivors and normal birth weight
      (NBW) controls, and (2) ascertain whether ANS functioning was differentially
      vulnerable to age-related decline in the ELBW participants. Resting HP and RSA
      (reflecting cardiac efficiency and responsive cardiac control, respectively) were
      assessed in 30 non-impaired ELBW survivors and 47 NBW controls at ages 22-26 and
      again at 30-35 years. At each assessment, resting RSA was significantly lower in
      the ELBW group than in the NBW comparison group. In addition, individual
      differences in RSA within the ELBW group were poorly preserved over time. These
      findings are suggestive of a premature decline in parasympathetic functioning in
      some adult ELBW survivors.

PMID- 24747728
TI  - Astroglial d-serine is the endogenous co-agonist at the presynaptic NMDA receptor
      in rat entorhinal cortex.
AB  - Presynaptic NMDA receptors facilitate the release of glutamate at excitatory
      cortical synapses and are involved in regulation of synaptic dynamics and
      plasticity. At synapses in the entorhinal cortex these receptors are tonically
      activated and provide a positive feedback modulation of the level of background
      excitation. NMDA receptor activation requires obligatory occupation of a co
      agonist binding site, and in the present investigation we have examined whether
      this site on the presynaptic receptor is activated by endogenous glycine or d
      serine. We used whole-cell patch clamp recordings of spontaneous AMPA receptor
      mediated synaptic currents from rat entorhinal cortex neurones in vitro as a
      monitor of presynaptic glutamate release. Addition of exogenous glycine or d
      serine had minimal effects on spontaneous release, suggesting that the co-agonist
      site was endogenously activated and likely to be saturated in our slices. This
      was supported by the observation that a co-agonist site antagonist reduced the
      frequency of spontaneous currents. Depletion of endogenous glycine by enzymatic
      breakdown with a bacterial glycine oxidase had little effect on glutamate
      release, whereas d-serine depletion with a yeast d-amino acid oxidase
      significantly reduced glutamate release, suggesting that d-serine is the
      endogenous agonist. Finally, the effects of d-serine depletion were mimicked by
      compromising astroglial cell function, and this was rescued by exogenous d
      serine, indicating that astroglial cells are the provider of the d-serine that
      tonically activates the presynaptic NMDA receptor. We discuss the significance of
      these observations for the aetiology of epilepsy and possible targeting of the
      presynaptic NMDA receptor in anticonvulsant therapy. 

PMID- 24747729
TI  - Deficient gaze pattern during virtual multiparty conversation in patients with
      schizophrenia.
AB  - Virtual reality has been used to measure abnormal social characteristics,
      particularly in one-to-one situations. In real life, however, conversations with
      multiple companions are common and more complicated than two-party conversations.
      In this study, we explored the features of social behaviors in patients with
      schizophrenia during virtual multiparty conversations. Twenty-three patients with
      schizophrenia and 22 healthy controls performed the virtual three-party
      conversation task, which included leading and aiding avatars, positive- and
      negative-emotion-laden situations, and listening and speaking phases. Patients
      showed a significant negative correlation in the listening phase between the
      amount of gaze on the between-avatar space and reasoning ability, and
      demonstrated increased gaze on the between-avatar space in the speaking phase
      that was uncorrelated with attentional ability. These results suggest that
      patients with schizophrenia have active avoidance of eye contact during three
      party conversations. Virtual reality may provide a useful way to measure abnormal
      social characteristics during multiparty conversations in schizophrenia. 

PMID- 24747730
TI  - An optimized Nash nonlinear grey Bernoulli model based on particle swarm
      optimization and its application in prediction for the incidence of Hepatitis B
      in Xinjiang, China.
AB  - In this paper, by using a particle swarm optimization algorithm to solve the
      optimal parameter estimation problem, an improved Nash nonlinear grey Bernoulli
      model termed PSO-NNGBM(1,1) is proposed. To test the forecasting performance, the
      optimized model is applied for forecasting the incidence of hepatitis B in
      Xinjiang, China. Four models, traditional GM(1,1), grey Verhulst model (GVM),
      original nonlinear grey Bernoulli model (NGBM(1,1)) and Holt-Winters exponential
      smoothing method, are also established for comparison with the proposed model
      under the criteria of mean absolute percentage error and root mean square percent
      error. The prediction results show that the optimized NNGBM(1,1) model is more
      accurate and performs better than the traditional GM(1,1), GVM, NGBM(1,1) and
      Holt-Winters exponential smoothing method. 

PMID- 24747731
TI  - Knocking down 10-Formyltetrahydrofolate dehydrogenase increased oxidative stress
      and impeded zebrafish embryogenesis by obstructing morphogenetic movement.
AB  - BACKGROUND: Folate is an essential nutrient for cell survival and embryogenesis.
      10-Formyltetrahydrofolate dehydrogenase (FDH) is the most abundant folate enzyme
      in folate-mediated one-carbon metabolism. 10-Formyltetrahydrofolate dehydrogenase
      converts 10-formyltetrahydrofolate to tetrahydrofolate and CO2, the only pathway
      responsible for formate oxidation in methanol intoxication. 10
      Formyltetrahydrofolate dehydrogenase has been considered a potential
      chemotherapeutic target because it was down-regulated in cancer cells. However,
      the normal physiological significance of 10-Formyltetrahydrofolate dehydrogenase
      is not completely understood, hampering the development of therapeutic
      drug/regimen targeting 10-Formyltetrahydrofolate dehydrogenase. METHODS: 10
      Formyltetrahydrofolate dehydrogenase expression in zebrafish embryos was knocked
      down using morpholino oligonucleotides. The morphological and biochemical
      characteristics of fdh morphants were examined using specific dye staining and
      whole-mount in-situ hybridization. Embryonic folate contents were determined by
      HPLC. RESULTS: The expression of 10-formyltetrahydrofolate dehydrogenase was
      consistent in whole embryos during early embryogenesis and became tissue-specific
      in later stages. Knocking-down fdh impeded morphogenetic movement and caused
      incorrect cardiac positioning, defective hematopoiesis, notochordmalformation and
      ultimate death of morphants. Obstructed F-actin polymerization and delayed
      epiboly were observed in fdh morphants. These abnormalities were reversed either
      by adding tetrahydrofolate or antioxidant or by co-injecting the mRNA encoding 10
      formyltetrahydrofolate dehydrogenase N-terminal domain, supporting the anti
      oxidative activity of 10-formyltetrahydrofolate dehydrogenase and the in vivo
      function of tetrahydrofolate conservation for 10-formyltetrahydrofolate
      dehydrogenase N-terminal domain. CONCLUSIONS: 10-Formyltetrahydrofolate
      dehydrogenase functioned in conserving the unstable tetrahydrofolate and
      contributing to the intracellular anti-oxidative capacity of embryos, which was
      crucial in promoting proper cell migration during embryogenesis. GENERAL
      SIGNIFICANCE: These newly reported tetrahydrofolate conserving and anti-oxidative
      activities of 10-formyltetrahydrofolate dehydrogenase shall be important for
      unraveling 10-formyltetrahydrofolate dehydrogenase biological significance and
      the drug development targeting 10-formyltetrahydrofolate dehydrogenase.

PMID- 24747732
TI  - Heparanase expression and localization in different types of human lung cancer.
AB  - BACKGROUND: Heparanase is the only known mammalian glycosidase capable of
      cleaving heparan sulfate chains. The expression of this enzyme has been
      associated with tumor development because of its ability to degrade extracellular
      matrix and promote cell invasion. METHODS: We analyzed heparanase expression in
      lung cancer samples to understand lung tumor progression and malignancy. Of the
      samples from 37 patients, there were 14 adenocarcinomas, 13 squamous cell
      carcinomas, 5 large cell carcinomas, and 5 small cell carcinomas.
      Immunohistochemistry was performed to ascertain the expression and localization
      of heparanase. RESULTS: All of the tumor types expressed heparanase, which was
      predominantly localized within the cytoplasm and nucleus. Significant enzyme
      expression was also observed in cells within the tumor microenvironment, such as
      fibroblasts, epithelial cells, and inflammatory cells. Adenocarcinomas exhibited
      the strongest heparanase staining intensity and the most widespread heparanase
      distribution. Squamous cell carcinomas, large cell carcinomas, and small cell
      carcinomas had a similar subcellular distribution of heparanase to
      adenocarcinomas but the distribution was less widespread. Heparanase expression
      tended to correlate with tumor node metastasis (TNM) staging in non-small cell
      lung carcinoma. CONCLUSION: In this study, we showed that heparanase was
      localized to the cytoplasm and nucleus of tumor cells and to cells within the
      microenvironment in different types of lung cancer. This enzyme exhibited a
      differential distribution based on the type of lung tumor. General significance
      Elucidating the heparanase expression patterns in different types of lung cancer
      increased our understanding of the crucial role of heparanase in lung cancer
      biology. This article is part of a Special Issue entitled Matrix-mediated cell
      behaviour and properties.

PMID- 24747733
TI  - Novel piezoelectric effect and surface plasmon resonance-based elements for MEMS
      applications.
AB  - This paper covers research on novel thin films with periodical microstructure-
      optical elements, exhibiting a combination of piezoelectric and surface plasmon
      resonance effects. The research results showed that incorporation of Ag
      nanoparticles in novel piezoelectric--plasmonic elements shift a dominating peak
      in the visible light spectrum. This optical window is essential in the design of
      optical elements for sensing systems. Novel optical elements can be tunable under
      defined bias and change its main grating parameters (depth and width) influencing
      the response of diffraction efficiencies. These elements allow opening new
      avenues in the design of more sensitive and multifunctional microdevices.

PMID- 24747734
TI  - An enhanced sensing application based on a flexible projected capacitive-sensing
      mattress.
AB  - This paper presents a cost-effective sensor system for mattresses that can
      classify the sleeping posture of an individual and prevent pressure ulcers. This
      system applies projected capacitive sensing to the field of health care. The
      charge time (CT) method was used to sensitively and accurately measure the
      capacitance of the projected electrodes. The required characteristics of the
      projected capacitor were identified to develop large-area applications for
      sensory mattresses. The area of the electrodes, the use of shielding, and the
      increased length of the transmission line were calibrated to more accurately
      measure the capacitance of the electrodes in large-size applications. To offer
      the users comfort in the prone position, a flexible substrate was selected and
      covered with 16 * 20 electrodes. Compared with the static charge sensitive bed
      (SCSB), our proposed system-flexible projected capacitive-sensing mattress
      (FPCSM) comes with more electrodes to increase the resolution of posture
      identification. As for the body pressure system (BPS), the FPCSM has advantages
      such as lower cost, higher aging-resistance capability, and the ability to sense
      the capacitance of the covered regions without physical contact. The proposed
      guard ring design effectively absorbs the noise and interrupts leakage paths. The
      projected capacitive electrode is suitable for proximity-sensing applications and
      succeeds at quickly recognizing the sleeping pattern of the user. 

PMID- 24747735
TI  - A discriminant distance based composite vector selection method for odor
      classification.
AB  - We present a composite vector selection method for an effective electronic nose
      system that performs well even in noisy environments. Each composite vector
      generated from a electronic nose data sample is evaluated by computing the
      discriminant distance. By quantitatively measuring the amount of discriminative
      information in each composite vector, composite vectors containing informative
      variables can be distinguished and the final composite features for odor
      classification are extracted using the selected composite vectors. Using the only
      informative composite vectors can be also helpful to extract better composite
      features instead of using all the generated composite vectors. Experimental
      results with different volatile organic compound data show that the proposed
      system has good classification performance even in a noisy environment compared
      to other methods. 

PMID- 24747736
TI  - Alpha and theta brain oscillations index dissociable processes in spoken word
      recognition.
AB  - Slow neural oscillations (~1-15 Hz) are thought to orchestrate the neural
      processes of spoken language comprehension. However, functional subdivisions
      within this broad range of frequencies are disputed, with most studies
      hypothesizing only about single frequency bands. The present study utilizes an
      established paradigm of spoken word recognition (lexical decision) to test the
      hypothesis that within the slow neural oscillatory frequency range, distinct
      functional signatures and cortical networks can be identified at least for theta-
      (~3-7 Hz) and alpha-frequencies (~8-12 Hz). Listeners performed an auditory
      lexical decision task on a set of items that formed a word-pseudoword continuum:
      ranging from (1) real words over (2) ambiguous pseudowords (deviating from real
      words only in one vowel; comparable to natural mispronunciations in speech) to
      (3) pseudowords (clearly deviating from real words by randomized syllables). By
      means of time-frequency analysis and spatial filtering, we observed a
      dissociation into distinct but simultaneous patterns of alpha power suppression
      and theta power enhancement. Alpha exhibited a parametric suppression as items
      increasingly matched real words, in line with lowered functional inhibition in a
      left-dominant lexical processing network for more word-like input.
      Simultaneously, theta power in a bilateral fronto-temporal network was
      selectively enhanced for ambiguous pseudowords only. Thus, enhanced alpha power
      can neurally 'gate' lexical integration, while enhanced theta power might index
      functionally more specific ambiguity-resolution processes. To this end, a joint
      analysis of both frequency bands provides neural evidence for parallel processes
      in achieving spoken word recognition.

PMID- 24747737
TI  - Optimizing full-brain coverage in human brain MRI through population
      distributions of brain size.
AB  - When defining an MRI protocol, brain researchers need to set multiple
      interdependent parameters that define repetition time (TR), voxel size, field-of
      view (FOV), etc. Typically, researchers aim to image the full brain, making the
      expected FOV an important parameter to consider. Especially in 2D-EPI sequences,
      non-wasteful FOV settings are important to achieve the best temporal and spatial
      resolution. In practice, however, imperfect FOV size estimation often results in
      partial brain coverage for a significant number of participants per study, or,
      alternatively, an unnecessarily large voxel-size or number of slices to guarantee
      full brain coverage. To provide normative FOV guidelines we estimated population
      distributions of brain size in the x-, y-, and z-direction using data from 14,781
      individuals. Our results indicated that 11mm in the z-direction differentiate
      between obtaining full brain coverage for 90% vs. 99.9% of participants.
      Importantly, we observed that rotating the FOV to optimally cover the brain, and
      thus minimize the number of slices needed, effectively reduces the required
      inferior-superior FOV size by ~5%. For a typical adult imaging study, 99.9% of
      the population can be imaged with full brain coverage when using an inferior
      superior FOV of 142mm, assuming optimal slice orientation and minimal within-scan
      head motion. By providing population distributions for brain size in the x-, y-,
      and z-direction we improve the potential for obtaining full brain coverage,
      especially in 2D-EPI sequences used in most functional and diffusion MRI studies.
      We further enable optimization of related imaging parameters including the number
      of slices, TR and total acquisition time. 

PMID- 24747738
TI  - Automatic clustering and population analysis of white matter tracts using maximum
      density paths.
AB  - We introduce a framework for population analysis of white matter tracts based on
      diffusion-weighted images of the brain. The framework enables extraction of
      fibers from high angular resolution diffusion images (HARDI); clustering of the
      fibers based partly on prior knowledge from an atlas; representation of the fiber
      bundles compactly using a path following points of highest density (maximum
      density path; MDP); and registration of these paths together using geodesic curve
      matching to find local correspondences across a population. We demonstrate our
      method on 4-Tesla HARDI scans from 565 young adults to compute localized
      statistics across 50 white matter tracts based on fractional anisotropy (FA).
      Experimental results show increased sensitivity in the determination of genetic
      influences on principal fiber tracts compared to the tract-based spatial
      statistics (TBSS) method. Our results show that the MDP representation reveals
      important parts of the white matter structure and considerably reduces the
      dimensionality over comparable fiber matching approaches. 

PMID- 24747739
TI  - Brain regions involved in processing facial identity and expression are
      differentially selective for surface and edge information.
AB  - Although different brain regions are widely considered to be involved in the
      recognition of facial identity and expression, it remains unclear how these
      regions process different properties of the visual image. Here, we ask how
      surface-based reflectance information and edge-based shape cues contribute to the
      perception and neural representation of facial identity and expression. Contrast
      reversal was used to generate images in which normal contrast relationships
      across the surface of the image were disrupted, but edge information was
      preserved. In a behavioural experiment, contrast-reversal significantly
      attenuated judgements of facial identity, but only had a marginal effect on
      judgements of expression. An fMR-adaptation paradigm was then used to ask how
      brain regions involved in the processing of identity and expression responded to
      blocks comprising all normal, all contrast-reversed, or a mixture of normal and
      contrast-reversed faces. Adaptation in the posterior superior temporal sulcus--a
      region directly linked with processing facial expression--was relatively
      unaffected by mixing normal with contrast-reversed faces. In contrast, the
      response of the fusiform face area--a region linked with processing facial
      identity--was significantly affected by contrast-reversal. These results offer a
      new perspective on the reasons underlying the neural segregation of facial
      identity and expression in which brain regions involved in processing invariant
      aspects of faces, such as identity, are very sensitive to surface-based cues,
      whereas regions involved in processing changes in faces, such as expression, are
      relatively dependent on edge-based cues.

PMID- 24747740
TI  - Insulin therapy modulates mitochondrial dynamics and biogenesis, autophagy and
      tau protein phosphorylation in the brain of type 1 diabetic rats.
AB  - The main purpose of this study was to examine whether streptozotocin (STZ)
      induced type 1 diabetes (T1D) and insulin (INS) treatment affect mitochondrial
      function, fission/fusion and biogenesis, autophagy and tau protein
      phosphorylation in cerebral cortex from diabetic rats treated or not with INS. No
      significant alterations were observed in mitochondrial function as well as
      pyruvate levels, despite the significant increase in glucose levels observed in
      INS-treated diabetic rats. A significant increase in DRP1 protein phosphorylated
      at Ser616 residue was observed in the brain cortex of STZ rats. Also an increase
      in NRF2 protein levels and in the number of copies of mtDNA were observed in STZ
      diabetic rats, these alterations being normalized by INS. A slight decrease in
      LC3-II levels was observed in INS-treated rats when compared to STZ diabetic
      animals. An increase in tau protein phosphorylation at Ser396 residue was
      observed in STZ diabetic rats while INS treatment partially reversed that effect.
      Accordingly, a modest reduction in the activation of GSK3beta and a significant
      increase in the activity of phosphatase 2A were found in INS-treated rats when
      compared to STZ diabetic animals. No significant alterations were observed in
      caspases 9 and 3 activity and synaptophysin and PSD95 levels. Altogether our
      results show that mitochondrial alterations induced by T1D seem to involve
      compensation mechanisms since no significant changes in mitochondrial function
      and synaptic integrity were observed in diabetic animals. In addition, INS
      treatment is able to normalize the alterations induced by T1D supporting the
      importance of INS signaling in the brain. 

PMID- 24747742
TI  - A practical implicit solvent potential for NMR structure calculation.
AB  - The benefits of protein structure refinement in water are well documented.
      However, performing structure refinement with explicit atomic representation of
      the solvent molecules is computationally expensive and impractical for NMR
      restrained structure calculations that start from completely extended polypeptide
      templates. Here we describe a new implicit solvation potential, EEFx (Effective
      Energy Function for XPLOR-NIH), for NMR-restrained structure calculations of
      proteins in XPLOR-NIH. The key components of EEFx are an energy term for
      solvation energy that works together with other nonbonded energy functions, and a
      dedicated force field for conformational and nonbonded protein interaction
      parameters. The initial results obtained with EEFx show that significant
      improvements in structural quality can be obtained. EEFx is computationally
      efficient and can be used both to fold and refine structures. Overall, EEFx
      improves the quality of protein conformation and nonbonded atomic interactions.
      Moreover, such benefits are accompanied by enhanced structural precision and
      enhanced structural accuracy, reflected in improved agreement with the cross
      validated dipolar coupling data. Finally, implementation of EEFx calculations is
      straightforward and computationally efficient. Overall, EEFx provides a useful
      method for the practical calculation of experimental protein structures in a
      physically realistic environment. 

PMID- 24747741
TI  - Is Alzheimer's disease a systemic disease?
AB  - Although Alzheimer's disease (AD) is the most common neurodegenerative disease,
      the etiology of AD is not well understood. In some cases, genetic factors explain
      AD risk, but a high percentage of late-onset AD is unexplained. The fact that AD
      is associated with a number of physical and systemic manifestations suggests that
      AD is a multifactorial disease that affects both the CNS and periphery.
      Interestingly, a common feature of many systemic processes linked to AD is
      involvement in energy metabolism. The goals of this review are to 1) explore the
      evidence that peripheral processes contribute to AD risk, 2) explore ways that AD
      modulates whole-body changes, and 3) discuss the role of genetics, mitochondria,
      and vascular mechanisms as underlying factors that could mediate both central and
      peripheral manifestations of AD. Despite efforts to strictly define AD as a
      homogeneous CNS disease, there may be no single etiologic pathway leading to the
      syndrome of AD dementia. Rather, the neurodegenerative process may involve some
      degree of baseline genetic risk that is modified by external risk factors.
      Continued research into the diverse but related processes linked to AD risk is
      necessary for successful development of disease-modifying therapies. 

PMID- 24747743
TI  - Consensus brain-derived protein, extraction protocol for the study of human and
      murine brain proteome using both 2D-DIGE and mini 2DE immunoblotting.
AB  - Two-dimensional gel electrophoresis (2DE) is a powerful tool to uncover proteome
      modifications potentially related to different physiological or pathological
      conditions. Basically, this technique is based on the separation of proteins
      according to their isoelectric point in a first step, and secondly according to
      their molecular weights by SDS polyacrylamide gel electrophoresis (SDS-PAGE). In
      this report an optimized sample preparation protocol for little amount of human
      post-mortem and mouse brain tissue is described. This method enables to perform
      both two-dimensional fluorescence difference gel electrophoresis (2D-DIGE) and
      mini 2DE immunoblotting. The combination of these approaches allows one to not
      only find new proteins and/or protein modifications in their expression thanks to
      its compatibility with mass spectrometry detection, but also a new insight into
      markers validation. Thus, mini-2DE coupled to western blotting permits to
      identify and validate post-translational modifications, proteins catabolism and
      provides a qualitative comparison among different conditions and/or treatments.
      Herein, we provide a method to study components of protein aggregates found in AD
      and Lewy body dementia such as the amyloid-beta peptide and the alpha-synuclein.
      Our method can thus be adapted for the analysis of the proteome and insoluble
      proteins extract from human brain tissue and mice models too. In parallel, it may
      provide useful information for the study of molecular and cellular pathways
      involved in neurodegenerative diseases as well as potential novel biomarkers and
      therapeutic targets. 

PMID- 24747744
TI  - The microbiota regulates neutrophil homeostasis and host resistance to
      Escherichia coli K1 sepsis in neonatal mice.
AB  - Neonatal colonization by microbes, which begins immediately after birth, is
      influenced by gestational age and the mother's microbiota and is modified by
      exposure to antibiotics. In neonates, prolonged duration of antibiotic therapy is
      associated with increased risk of late-onset sepsis (LOS), a disorder controlled
      by neutrophils. A role for the microbiota in regulating neutrophil development
      and susceptibility to sepsis in the neonate remains unclear. We exposed pregnant
      mouse dams to antibiotics in drinking water to limit transfer of maternal
      microbes to the neonates. Antibiotic exposure of dams decreased the total number
      and composition of microbes in the intestine of the neonates. This was associated
      with decreased numbers of circulating and bone marrow neutrophils and
      granulocyte/macrophage-restricted progenitor cells in the bone marrow of
      antibiotic-treated and germ-free neonates. Antibiotic exposure of dams reduced
      the number of interleukin-17 (IL-17)-producing cells in the intestine and
      production of granulocyte colony-stimulating factor (G-CSF). Granulocytopenia was
      associated with impaired host defense and increased susceptibility to Escherichia
      coli K1 and Klebsiella pneumoniae sepsis in antibiotic-treated neonates, which
      could be partially reversed by administration of G-CSF. Transfer of a normal
      microbiota into antibiotic-treated neonates induced IL-17 production by group 3
      innate lymphoid cells (ILCs) in the intestine, increasing plasma G-CSF levels and
      neutrophil numbers in a Toll-like receptor 4 (TLR4)- and myeloid differentiation
      factor 88 (MyD88)-dependent manner and restored IL-17-dependent resistance to
      sepsis. Specific depletion of ILCs prevented IL-17- and G-CSF-dependent
      granulocytosis and resistance to sepsis. These data support a role for the
      intestinal microbiota in regulation of granulocytosis, neutrophil homeostasis and
      host resistance to sepsis in neonates. 

PMID- 24747745
TI  - Essential role for autophagy in the maintenance of immunological memory against
      influenza infection.
AB  - Vaccination has been the most widely used strategy to protect against viral
      infections for centuries. However, the molecular mechanisms governing the long
      term persistence of immunological memory in response to vaccines remain unclear.
      Here we show that autophagy has a critical role in the maintenance of memory B
      cells that protect against influenza virus infection. Memory B cells displayed
      elevated levels of basal autophagy with increased expression of genes that
      regulate autophagy initiation or autophagosome maturation. Mice with B cell
      specific deletion of Atg7 (B/Atg7(-/-) mice) showed normal primary antibody
      responses after immunization against influenza but failed to generate protective
      secondary antibody responses when challenged with influenza viruses, resulting in
      high viral loads, widespread lung destruction and increased fatality. Our results
      suggest that autophagy is essential for the survival of virus-specific memory B
      cells in mice and the maintenance of protective antibody responses required to
      combat infections. 

PMID- 24747746
TI  - Pten deletion in RIP-Cre neurons protects against type 2 diabetes by activating
      the anti-inflammatory reflex.
AB  - Inflammation has a critical role in the development of insulin resistance. Recent
      evidence points to a contribution by the central nervous system in the modulation
      of peripheral inflammation through the anti-inflammatory reflex. However, the
      importance of this phenomenon remains elusive in type 2 diabetes pathogenesis.
      Here we show that rat insulin-2 promoter (Rip)-mediated deletion of Pten, a gene
      encoding a negative regulator of PI3K signaling, led to activation of the
      cholinergic anti-inflammatory pathway that is mediated by M2 activated
      macrophages in peripheral tissues. As such, Rip-cre(+) Pten(flox/flox) mice
      showed lower systemic inflammation and greater insulin sensitivity under basal
      conditions compared to littermate controls, which were abolished when the mice
      were treated with an acetylcholine receptor antagonist or when macrophages were
      depleted. After feeding with a high-fat diet, the Pten-deleted mice remained
      markedly insulin sensitive, which correlated with massive subcutaneous fat
      expansion. They also exhibited more adipogenesis with M2 macrophage infiltration,
      both of which were abolished after disruption of the anti-inflammatory efferent
      pathway by left vagotomy. In summary, we show that Pten expression in Rip(+)
      neurons has a critical role in diabetes pathogenesis through mediating the anti
      inflammatory reflex. 

PMID- 24747748
TI  - Inhibition of tumor cell growth and angiogenesis by 7-aminoalkoxy-4-aryloxy
      quinazoline ureas, a novel series of multi-tyrosine kinase inhibitors.
AB  - Several regulatory and signaling molecules governing angiogenesis are targets of
      interest for the development of drugs in the cancer, including growth factors
      such as Vascular Endothelial Growth Factor (VEGF) and Platelet-Derived Growth
      Factor (PDGF). A series of 4-aryloxy-6,7-dimethoxyquinazolines, previously
      synthesized in our laboratory, has shown a nanomolar inhibition of kinase
      enzymatic activity of VEGFR, PDGFR and c-Kit. We have therefore studied the
      impact of the variation in the 7-position substitution of the quinazoline core.
      Substitution by aminoalkoxy chains led to new highly potent ATP-competitive
      inhibitors of VEGFR, PDGFR and c-Kit enzyme with IC50 values in the nanomolar
      range and this substitution has increased greatly antiproliferative activity on
      cancer cell lines (PC3, MCF7, HT29) and HUVEC (human umbilical vein endothelial
      cells). One of the most promising compounds (36) was assessed for its ability to
      limit the induction of web like network of capillary tubes by the human umbilical
      vascular endothelial cells (HUVEC) and for its ability to inhibit invasion. 

PMID- 24747747
TI  - Multiparametric optical analysis of mitochondrial redox signals during neuronal
      physiology and pathology in vivo.
AB  - Mitochondrial redox signals have a central role in neuronal physiology and
      disease. Here we describe a new optical approach to measure fast redox signals
      with single-organelle resolution in living mice that express genetically encoded
      redox biosensors in their neuronal mitochondria. Moreover, we demonstrate how
      parallel measurements with several biosensors can integrate these redox signals
      into a comprehensive characterization of mitochondrial function. This approach
      revealed that axonal mitochondria undergo spontaneous 'contractions' that are
      accompanied by reversible redox changes. These contractions are amplified by
      neuronal activity and acute or chronic neuronal insults. Multiparametric imaging
      reveals that contractions constitute respiratory chain-dependent episodes of
      depolarization coinciding with matrix alkalinization, followed by uncoupling. In
      contrast, permanent mitochondrial damage after spinal cord injury depends on
      calcium influx and mitochondrial permeability transition. Thus, our approach
      allows us to identify heterogeneity among physiological and pathological redox
      signals, correlate such signals to functional and structural organelle dynamics
      and dissect the underlying mechanisms. 

PMID- 24747749
TI  - Substituted E-3-(3-indolylmethylene)1,3-dihydroindol-2-ones with
      antiproliferative activity. Study of the effects on HL-60 leukemia cells.
AB  - The synthesis of new substituted E-3-(3-indolylmethylene)1,3-dihydroindol-2-ones
      is reported. The antiproliferative activity was evaluated according to protocols
      available at the National Cancer Institute (NCI), Bethesda, MD. The action of the
      most active compound 10 was further investigated in HL-60 leukemia cells. Results
      obtained show that it causes a block in cell cycle progression, with cell arrest
      in the G2/M phase, associated with activation of apoptosis accompanied with
      increased oxidative stress and deregulation of the homeostasis of divalent
      cations, with significant increase in the cellular concentrations of free Ca(2+)
      and Mg(2+). 

PMID- 24747750
TI  - Synthesis, characterization and anti-proliferative activity of heterocyclic
      hypervalent organoantimony compounds.
AB  - Three heterocyclic hypervalent organoantimony chlorides RN(CH2C6H4)2SbCl (2a R =
      t-Bu, 2b R = Cy, 2c R = Ph) and their chalcogenide derivatives [RN(CH2C6H4)2Sb]2O
      (3a R = t-Bu, 3b R = Cy, 3c R = Ph) were synthesized and characterized by
      techniques such as (1)H NMR, (13)C NMR, X-ray diffraction, and elemental
      analysis. It is found that the anti-proliferative activity detected over these
      compounds can be attributed to the coordination bond between the antimony and
      nitrogen atoms of these compounds. Moreover, a preliminary study on mechanistic
      action suggests that the inhibition effect is ascribable to cell cycle arrest and
      cell apoptosis. 

PMID- 24747751
TI  - Pharmacologic profiles of investigational kisspeptin/metastin analogues, TAK-448
      and TAK-683, in adult male rats in comparison to the GnRH analogue leuprolide.
AB  - Kisspeptin/metastin, a hypothalamic peptide, plays a pivotal role in controlling
      gonadotropin-releasing hormone (GnRH) neurons, and we have shown that continuous
      subcutaneous administration of kisspeptin analogues suppresses plasma
      testosterone in male rats. This study examined pharmacologic profiles of
      investigational kisspeptin analogues, TAK-448 and TAK-683, in male rats. Both
      analogues showed high receptor-binding affinity and potent and full agonistic
      activity for rat KISS1R, which were comparable to natural peptide Kp-10. A daily
      subcutaneous injection of TAK-448 and TAK-683 (0.008-8MUmol/kg) for consecutive 7
      days initially induced an increase in plasma luteinizing hormone and testosterone
      levels; however, after day 7, plasma hormone levels and genital organ weights
      were reduced. Continuous subcutaneous administrations of TAK-448 (>=10pmol/h, ca.
      0.7nmol/kg/day) and TAK-683 (>=30pmol/h, ca. 2.1nmol/kg/day) induced a transient
      increase in plasma testosterone, followed by abrupt reduction of plasma
      testosterone to castrate levels within 3-7 days. This profound testosterone
      lowering effect was sustained throughout 4-week dosing periods. At those dose
      levels, the weights of the prostate and seminal vesicles were reduced to castrate
      levels. These suppressive effects of kisspeptin analogues were more rapid and
      profound than those induced by the GnRH agonist analogue leuprolide treatment. In
      addition, TAK-683 reduced plasma prostate specific antigen (PSA) in the JDCaP
      androgen-dependent prostate cancer rat model. Thus, chronic administration of
      kisspeptin analogues may hold promise as a novel therapeutic approach for
      suppressing reproductive functions and hormone-related diseases such as prostate
      cancer. Further studies are warranted to elucidate clinical significance of TAK
      448 and TAK-683. 

PMID- 24747752
TI  - Stimulation of large-conductance calcium-activated potassium channels inhibits
      neurogenic contraction of human bladder from patients with urinary symptoms and
      reverses acetic acid-induced bladder hyperactivity in rats.
AB  - We have analysed the effects of large-conductance calcium-activated potassium
      channel (BK) stimulation on neurogenic and myogenic contraction of human bladder
      from healthy subjects and patients with urinary symptoms and evaluated the
      efficacy of activating BK to relief bladder hyperactivity in rats. Bladder
      specimens were obtained from organ donors and from men with benign prostatic
      hyperplasia (BPH). Contractions elicited by electrical field stimulation (EFS)
      and carbachol (CCh) were evaluated in isolated bladder strips. in vivo
      cystometric recordings were obtained in anesthetized rats under control and
      acetic acid-induced hyperactive conditions. Neurogenic contractions of human
      bladder were potentiated by blockade of BK and small-conductance calcium
      activated potassium channels (SK) but were unaffected by the blockade of
      intermediate calcium-activated potassium channels (IK). EFS-induced contractions
      were inhibited by BK stimulation with NS-8 or NS1619 or by SK/IK stimulation with
      NS309 (3uM). CCh-induced contractions were not modified by blockade or
      stimulation of BK, IK or SK. The anti-cholinergic agent, oxybutynin (0.3uM)
      inhibited either neurogenic or CCh-induced contractions. Neurogenic contractions
      of bladders from BPH patients were less sensitive to BK inhibition and more
      sensitive to BK activation than healthy bladders. The BK activator, NS-8 (5mg/kg;
      i.v.), reversed bladder hyperactivity induced by acetic acid in rats, while
      oxybutynin was ineffective. NS-8 did not significantly impact blood pressure or
      heart rate. BK stimulation specifically inhibits neurogenic contractions in
      patients with urinary symptoms and relieves bladder hyperactivity in vivo without
      compromising bladder contractile capacity or cardiovascular safety, supporting
      its potential therapeutic use for relieving bladder overactivity. 

PMID- 24747753
TI  - Antidepressant and anti-anxiety like effects of 4i (N-(3-chloro-2-methylphenyl)
      quinoxalin-2-carboxamide), a novel 5-HT3 receptor antagonist in acute and chronic
      neurobehavioral rodent models.
AB  - Depression and anxiety are the most debilitating mood disorders with poor
      therapeutic recovery rates. In the last decades, 5-HT3 receptor antagonists have
      been identified as potential agents for mood disorders. The current investigation
      focuses on evaluating the, antidepressant and anti-anxiety like effects of a
      novel 5-HT3 antagonist, 4i (N-(3-chloro-2-methylphenyl) quinoxalin-2
      carboxamide). Preliminary, in vitro 5-HT3 receptor binding affinity was performed
      in isolated longitudinal muscle-myenteric plexus from the guinea pig ileum.
      Consequently, neurobehavioral effects of 4i in acute and chronic rodent models
      were evaluated. In addition, involvement of serotonergic system in the postulated
      effects of the compound was analyzed by in vivo assay. in vitro, 4i demonstrated
      high 5-HT3 receptor antagonistic activity (pA2, 7.6). in vivo acute study, 4i
      exhibited decreased duration of immobility in forced swim and tail suspension
      tests, and increased exploratory parameters as number and duration of nose-poking
      in hole board test and latency and time spent in aversive brightly illuminated
      light chamber in light-dark model. Moreover, in chronic model of depression,
      i.e., olfactory bulbectomy with behavioral deficits, 4i reversed depressive
      anhedonia in sucrose preference test and anxious hyperactive behavior in open
      field test in rats. Furthermore, synergistic effect of 4i with fluoxetine (a
      selective serotonin reuptake inhibitor) and inhibitory effect of 1-(m
      chlorophenyl)-biguanide (a 5-HT3 receptor agonist) revealed serotonergic
      modulation by 4i mediated 5-HT3 receptor antagonism, which was further confirmed
      by potentiation of 5-hydroxytryptophan (a serotonin synthesis precursor) induced
      head twitch response. These findings suggest the potential antidepressant and
      anti-anxiety like effects of 4i, which may be related to the modulation of
      serotonergic system. 

PMID- 24747754
TI  - Diaphragmatic neuromechanical coupling and mechanisms of hypercapnia during
      inspiratory loading.
AB  - We hypothesized that improved diaphragmatic neuromechanical coupling during
      inspiratory loading is not sufficient to prevent alveolar hypoventilation and
      task failure, and that the latter results primarily from central-output
      inhibition of the diaphragm and air hunger rather than contractile fatigue.
      Eighteen subjects underwent progressive inspiratory loading. By task failure all
      developed hypercapnia. Tidal transdiaphragmatic pressure (DeltaPdi) and
      diaphragmatic electrical activity (DeltaEAdi) increased during loading - the
      former more than the latter; thus, neuromechanical coupling (DeltaPdi/DeltaEAdi)
      increased during loading. Progressive increase in extra-diaphragmatic muscle
      contribution to tidal breathing, expiratory muscle recruitment, and decreased end
      expiratory lung volume contributed to improved neuromechanical coupling. At task
      failure, subjects experienced intolerable breathing discomfort, at which point
      mean DeltaEAdi was 74.9+/-4.9% of maximum, indicating that the primary mechanism
      of hypercapnia was submaximal diaphragmatic recruitment. Contractile fatigue was
      an inconsistent finding. In conclusion, hypercapnia during acute loading
      primarily resulted from central-output inhibition of the diaphragm suggesting
      that acute loading responses are controlled by the cortex rather than
      bulbopontine centers. 

PMID- 24747755
TI  - Antral hyperplastic polyp: A rare cause of gastric outlet obstruction.
AB  - INTRODUCTION: Gastric polyps are usually found incidentally during upper
      gastrointestinal endoscopic examinations. These polyps are generally benign, with
      hyperplasia being the most common. While gastric polyps are often asymptomatic,
      they can cause gastric outlet obstruction. PRESENTATION OF CASE: A 64 years-old
      female patient presented to our polyclinic with a history of approximately 2
      months of weakness, occasional early nausea, vomiting after meals and epigastric
      pain. A polypoid lesion of approximately 25mm in diameter was detected in the
      antral area of the stomach, which prolapsed through the pylorus into the duodenal
      bulbus, and subsequently caused gastric outlet obstruction, as revealed by upper
      gastrointestinal endoscopy of the patient. The polyp was retrieved from the
      pyloric canal into the stomach with the aid of a tripod, and snare polypectomy
      was performed. DISCUSSION: Currently, widespread use of endoscopy has led to an
      increase in the frequency of detecting hyperplastic polyps. While most gastric
      polyps are asymptomatic, they can cause iron deficiency anemia, acute
      pancreatitis and more commonly, gastric outlet obstruction because of their
      antral location. Although there are no precise principles in the treatment of
      asymptomatic polyps, polyps >5mm should be removed due to the possibility of
      malignant transformation. CONCLUSION: According to the medical evidence,
      polypectomy is required for gastric hyperplastic polyps because of the risks of
      complication and malignancy. These cases can be successfully treated
      endoscopically.

PMID- 24747756
TI  - Phyllodes tumor metastasis to the tonsil with synchronous undifferentiated
      carcinoma.
AB  - INTRODUCTION: Breast tumor metastasis to the tonsil is extremely rare.
      PRESENTATION OF CASE: A 54-year-old woman underwent resection of a breast
      malignant phyllodes tumor and later presented with metastasis to the lung and the
      left tonsil. She underwent left lower lobectomy and resection of the left
      tonsillar tumor. She subsequently developed undifferentiated carcinoma of the
      right tonsil. She underwent resection of the right tonsillar tumor and
      chemotherapy was started. The central venous catheter became infected with
      methicillin-resistant Staphylococcus aureus. Finally, she died. DISCUSSION: To
      the best of our knowledge, this is the first reported case of a phyllodes tumor
      metastasizing to the tonsil. Furthermore, morphological and immunohistochemical
      study revealed that the right tonsillar tumor was irrelevant to the phyllodes
      tumors. CONCLUSION: We report a case of phyllodes tumor metastasis to the left
      tonsil which developed undifferentiated carcinoma in the other side of tonsil
      later. Breast tumor metastasis to the tonsil is rare but it should be considered
      as a possible diagnosis.

PMID- 24747757
TI  - Mouse genome engineering using designer nucleases.
AB  - Transgenic mice carrying site-specific genome modifications (knockout, knock-in)
      are of vital importance for dissecting complex biological systems as well as for
      modeling human diseases and testing therapeutic strategies. Recent advances in
      the use of designer nucleases such as zinc finger nucleases (ZFNs), transcription
      activator-like effector nucleases (TALENs), and the clustered regularly
      interspaced short palindromic repeats (CRISPR)/CRISPR-associated (Cas) 9 system
      for site-specific genome engineering open the possibility to perform rapid
      targeted genome modification in virtually any laboratory species without the need
      to rely on embryonic stem (ES) cell technology. A genome editing experiment
      typically starts with identification of designer nuclease target sites within a
      gene of interest followed by construction of custom DNA-binding domains to direct
      nuclease activity to the investigator-defined genomic locus. Designer nuclease
      plasmids are in vitro transcribed to generate mRNA for microinjection of
      fertilized mouse oocytes. Here, we provide a protocol for achieving targeted
      genome modification by direct injection of TALEN mRNA into fertilized mouse
      oocytes. 

PMID- 24747758
TI  - The N-terminal domain of the repressor of Staphylococcus aureus phage Phi11
      possesses an unusual dimerization ability and DNA binding affinity.
AB  - Bacteriophage Phi11 uses Staphylococcus aureus as its host and, like lambdoid
      phages, harbors three homologous operators in between its two divergently
      oriented repressor genes. None of the repressors of Phi11, however, showed
      binding to all three operators, even at high concentrations. To understand why
      the DNA binding mechanism of Phi11 repressors does not match that of lambdoid
      phage repressors, we studied the N-terminal domain of the Phi11 lysogenic
      repressor, as it harbors a putative helix-turn-helix motif. Our data revealed
      that the secondary and tertiary structures of the N-terminal domain were
      different from those of the full-length repressor. Nonetheless, the N-terminal
      domain was able to dimerize and bind to the operators similar to the intact
      repressor. In addition, the operator base specificity, binding stoichiometry, and
      binding mechanism of this domain were nearly identical to those of the whole
      repressor. The binding affinities of the repressor and its N-terminal domain were
      reduced to a similar extent when the temperature was increased to 42 degrees C.
      Both proteins also adequately dislodged a RNA polymerase from a Phi11 DNA
      fragment carrying two operators and a promoter. Unlike the intact repressor, the
      binding of the N-terminal domain to two adjacent operator sites was not
      cooperative in nature. Taken together, we suggest that the dimerization and DNA
      binding abilities of the N-terminal domain of the Phi11 repressor are distinct
      from those of the DNA binding domains of other phage repressors. 

PMID- 24747759
TI  - Efficient molecular marker design using the MaizeGDB Mo17 SNPs and Indels track.
AB  - Positional cloning in maize (Zea mays) requires development of markers in the
      region of interest. We found that primers designed to amplify annotated insertion
      deletion polymorphisms of seven base pairs or greater between B73 and Mo17
      produce polymorphic markers at a 97% frequency with 49% of the products showing
      co-dominant fragment length polymorphisms. When the same polymorphisms are used
      to develop markers for B73 and W22 or Mo17 and W22 mapping populations, 22% and
      31% of markers are co-dominant, respectively. There are 38,223 Indel
      polymorphisms that can be converted to markers providing high-density coverage
      throughout the maize genome. This strategy significantly increases the efficiency
      of marker development for fine-mapping in maize. 

PMID- 24747760
TI  - A strategy to identify dominant point mutant modifiers of a quantitative trait.
AB  - A central goal in the analysis of complex traits is to identify genes that modify
      a phenotype. Modifiers of a cancer phenotype may act either intrinsically or
      extrinsically on the salient cell lineage. Germline point mutagenesis by
      ethylnitrosourea can provide alleles for a gene of interest that include loss-,
      gain-, or alteration-of-function. Unlike strain polymorphisms, point mutations
      with heterozygous quantitative phenotypes are detectable in both essential and
      nonessential genes and are unlinked from other variants that might confound their
      identification and analysis. This report analyzes strategies seeking quantitative
      mutational modifiers of Apc(Min) in the mouse. To identify a quantitative
      modifier of a phenotype of interest, a cluster of test progeny is needed. The
      cluster size can be increased as necessary for statistical significance if the
      founder is a male whose sperm is cryopreserved. A second critical element in this
      identification is a mapping panel free of polymorphic modifiers of the phenotype,
      to enable low-resolution mapping followed by targeted resequencing to identify
      the causative mutation. Here, we describe the development of a panel of six
      "isogenic mapping partner lines" for C57BL/6J, carrying single-nucleotide markers
      introduced by mutagenesis. One such derivative, B6.SNVg, shown to be
      phenotypically neutral in combination with Apc(Min), is an appropriate mapping
      partner to locate induced mutant modifiers of the Apc(Min) phenotype. The evolved
      strategy can complement four current major initiatives in the genetic analysis of
      complex systems: the Genome-wide Association Study; the Collaborative Cross; the
      Knockout Mouse Project; and The Cancer Genome Atlas. 

PMID- 24747762
TI  - Macrophage-targeted delivery systems for nucleic acid therapy of inflammatory
      diseases.
AB  - Inflammation is an immune response that marks several pathophysiological
      conditions in our body. Though adaptive immune cells play a major role in the
      progression of the disease, components of innate immune system, mainly monocytes
      and macrophages play the central role in onset of inflammation. Tissue-associated
      macrophages are widely distributed in the body showing tremendous anatomical and
      functional diversity and are actively involved in maintaining the homeostasis.
      They exhibit different phenotypes depending on their residing tissue
      microenvironment and the two major functional phenotypes are classically
      activated M1 phenotype showing pro-inflammatory characteristics and alternatively
      activated M2 phenotype demonstrating anti-inflammatory nature. Several cytokines,
      chemokines and other regulatory mediators delicately govern the balance of the
      two phenotypes in a tissue. This balance, however, is subverted during infection,
      injury or autoimmune response leading to increased population of M1 phenotype and
      subsequent chronic inflammatory disease states. This review underlines the role
      of macrophages in inflammatory diseases with an insight into potential molecular
      targets for nucleic acid therapy. Finally, some recent nanotechnology-based
      approaches to devise macrophage-specific targeted therapy have been highlighted. 

PMID- 24747763
TI  - WITHDRAWN: A clinical update of using albumin as a drug vehicle - A commentary.
AB  - The Publisher regrets that this article is an accidental duplication of an
      article that has already been published,
      http://dx.doi.org/10.1016/j.jconrel.2014.03.013. The duplicate article has
      therefore been withdrawn.

PMID- 24747761
TI  - Hydrodynamic delivery of FGF21 gene alleviates obesity and fatty liver in mice
      fed a high-fat diet.
AB  - FGF21 is a secreted protein that plays critical roles in regulating glucose and
      lipid metabolism. In this study, we evaluated the effects of FGF21 gene transfer
      on C57BL/6 mice fed a high fat diet (HFD). We demonstrate that transfer of the
      FGF21 gene using a hydrodynamics-based procedure increased mRNA levels of FGF21
      exclusively in the liver, consequently generating a sustained high level of FGF21
      protein in blood that peaked at 500 ng/ml 1 day after injection, leading to a
      variety of beneficial effects including blockade of HFD-induced obesity,
      alleviation of fatty liver and improvement in glucose homeostasis. These effects
      were associated with altered expression of Ucp1, Dio2, Pgc1alpha, Ppargamma2,
      Mgat1, F4/80, Mcp1 and Tnfalpha, which are involved in thermogenesis, lipogenesis
      and chronic inflammation in the liver and adipose tissues. Transfer of the FGF21
      gene in HFD-induced obese mice greatly increased the expression of thermogenic
      genes in adipose tissue, resulting in similar improvements in systemic metabolism
      including reduction of adiposity, alleviation of fatty liver and attenuation of
      insulin resistance. Mechanistic studies on the effects of FGF21 gene transfer in
      lean mice revealed that mice transferred with FGF21 gene displayed suppressed
      lipogenesis in the liver and enhanced thermogenesis in brown adipose tissue which
      was coincident with a significant improvement in glucose tolerance. Collectively,
      our results suggest that transfer of the FGF21 gene could be considered a
      promising approach for treating obesity and its complications.

PMID- 24747764
TI  - WITHDRAWN: Vision, launch and early days of Journal of Controlled Release.
AB  - The Publisher regrets that this article is an accidental duplication of an
      article that has already been published,
      http://dx.doi.org/10.1016/j.jconrel.2014.03.010. The duplicate article has
      therefore been withdrawn.

PMID- 24747765
TI  - Nano-niosomes as nanoscale drug delivery systems: an illustrated review.
AB  - The field of nanochemistry research has shown a great progress in the developing
      of novel nanocarriers as potential drug delivery systems. Niosome is a class of
      molecular cluster formed by self-association of non-ionic surfactants in an
      aqueous phase. The unique structure of niosome presents an effective novel drug
      delivery system (NDDS) with ability of loading both hydrophilic and lipophilic
      drugs. Numerous research articles have been published in scientific journals,
      reporting valuable results of individual case studies in this context. However,
      surveying and discussing the recent, rapidly growing reported studies along with
      their theoretical principals is required for the fully understanding and
      exploring the great potential of this approach. To this aim, we have provided an
      illustrated and comprehensive study from the view of a supramolecular chemist,
      interested in the synthesizing and studying chemical aggregates on the nanoscale
      for the development of nanotechnological clusters including niosomes. First, a
      connectional review of the molecular structure and physicochemical properties of
      niosome forming non-ionic surfactants and additive agents have been discussed.
      Second, a systematic survey of niosome preparation and loading methods,
      administration routes, characterization of niosomes, their toxicity studies and
      mechanism of drug release; used in recent articles have been performed. 

PMID- 24747766
TI  - A longitudinal linear model of patient characteristics to predict failure to
      attend an inner-city chronic pain clinic.
AB  - Patients often fail to attend appointments in chronic pain clinics for unknown
      reasons. We hypothesized that certain patient characteristics predict failure to
      attend scheduled appointments, pointing to systematic barriers to accessing
      chronic pain services for certain underserved populations. We collected
      retrospective data from a longitudinal observational cohort of patients at an
      academic pain clinic in Newark, New Jersey. To examine the effect of demographic
      factors on appointment status, we fit a marginal logistic regression using
      generalized estimating equations with exchangeable correlation. A total of 1,394
      patients with 3,488 total encounters between January 1, 2006, and December 31,
      2009, were included. Spanish spoken as a primary language (alternatively Hispanic
      or other race) and living between 5 and 10 miles from the clinic were associated
      with reduced odds of arriving for an appointment; making an appointment for a
      particular complaint such as cancer pain or back pain, an interventional pain
      procedure scheduled in connection with the appointment, unemployed status, and
      continuity of care (as measured by office visit number) were associated with
      increased odds of arriving. Spanish spoken as a primary language and distance to
      the pain clinic predicted failure to attend a scheduled appointment in our
      cohort. If these constitute systematic barriers to access, they may be amenable
      to targeted interventions. PERSPECTIVE: We identified certain patient
      characteristics, specifically Spanish spoken as a primary language and geographic
      distance from the clinic, that predict failure to attend an inner-city chronic
      pain clinic. These identified barriers to accessing chronic pain services may be
      modifiable by simple cost-effective interventions.

PMID- 24747767
TI  - Population structure among mycobacterium tuberculosis isolates from pulmonary
      tuberculosis patients in Colombia.
AB  - BACKGROUND: Phylogeographic composition of M. tuberculosis populations reveals
      associations between lineages and human populations that might have implications
      for the development of strategies to control the disease. In Latin America,
      lineage 4 or the Euro-American, is predominant with considerable variations among
      and within countries. In Colombia, although few studies from specific localities
      have revealed differences in M. tuberculosis populations, there are still areas
      of the country where this information is lacking, as is a comparison of Colombian
      isolates with those from the rest of the world. PRINCIPAL FINDINGS: A total of
      414 M. tuberculosis isolates from adult pulmonary tuberculosis cases from three
      Colombian states were studied. Isolates were genotyped using IS6110-restriction
      fragment length polymorphism (RFLP), spoligotyping, and 24-locus Mycobacterial
      interspersed repetitive units variable number tandem repeats (MIRU-VNTRs). SIT42
      (LAM9) and SIT62 (H1) represented 53.3% of isolates, followed by 8.21% SIT50
      (H3), 5.07% SIT53 (T1), and 3.14% SIT727 (H1). Composite spoligotyping and 24
      locus MIRU- VNTR minimum spanning tree analysis suggest a recent expansion of
      SIT42 and SIT62 evolved originally from SIT53 (T1). The proportion of Haarlem
      sublineage (44.3%) was significantly higher than that in neighboring countries.
      Associations were found between M. tuberculosis MDR and SIT45 (H1), as well as
      HIV-positive serology with SIT727 (H1) and SIT53 (T1). CONCLUSIONS: This study
      showed the population structure of M. tuberculosis in several regions from
      Colombia with a dominance of the LAM and Haarlem sublineages, particularly in two
      major urban settings (Medellin and Cali). Dominant spoligotypes were LAM9 (SIT
      42) and Haarlem (SIT62). The proportion of the Haarlem sublineage was higher in
      Colombia compared to that in neighboring countries, suggesting particular
      conditions of co-evolution with the corresponding human population that favor the
      success of this sublineage.

PMID- 24747768
TI  - Glutamate as chemotactic fuel for diffuse glioma cells: are they glutamate
      suckers?
AB  - Diffuse gliomas comprise a group of primary brain tumors that originate from
      glial (precursor) cells and present as a variety of malignancy grades which have
      in common that they grow by diffuse infiltration. This phenotype complicates
      treatment enormously as it precludes curative surgery and radiotherapy.
      Furthermore, diffusely infiltrating glioma cells often hide behind a functional
      blood-brain barrier, hampering delivery of systemically administered therapeutic
      and diagnostic compounds to the tumor cells. The present review addresses the
      biological mechanisms that underlie the diffuse infiltrative phenotype, knowledge
      of which may improve treatment strategies for this disastrous tumor type. The
      invasive phenotype is specific for glioma: most other brain tumor types, both
      primary and metastatic, grow as delineated lesions. Differences between the
      genetic make-up of glioma and that of other tumor types may therefore help to
      unravel molecular pathways, involved in diffuse infiltrative growth. One such
      difference concerns mutations in the NADP(+)-dependent isocitrate dehydrogenase
      (IDH1 and IDH2) genes, which occur in >80% of cases of low grade glioma and
      secondary glioblastoma. In this review we present a novel hypothesis which links
      IDH1 and IDH2 mutations to glutamate metabolism, possibly explaining the specific
      biological behavior of diffuse glioma. 

PMID- 24747770
TI  - Effects of representative glucocorticoids on TNFalpha- and CD40L-induced NF
      kappaB activation in sensor cells.
AB  - Glucocorticoids are an important class of anti-inflammatory/immunosuppressive
      drugs. A crucial part of their anti-inflammatory action results from their
      ability to repress proinflammatory transcription factors such as nuclear factor
      kappaB (NF-kappaB) and activator protein-1 (AP-1) upon binding to the
      glucocorticoid receptor (GR). Accordingly, sensor cells quantifying their effect
      on inflammatory signal-induced NF-kappaB activation can provide useful
      information regarding their potencies as well as their transrepression abilities.
      Here, we report results obtained on their effect in suppressing both the TNFalpha
      and the CD40L-induced activation of NF-kappaB in sensor cells that contain an NF
      kappaB-inducible SEAP construct. In these cells, we confirmed concentration
      dependent NF-kappaB activation for both TNFalpha and CD40L at low nanomolar
      concentrations (EC50). Glucocorticoids tested included hydrocortisone,
      prednisolone, dexamethasone, loteprednol etabonate, triamcinolone acetonide,
      beclomethasone dipropionate, and clobetasol propionate. They all caused
      significant, but only partial inhibition of these activations in concentration
      dependent manners that could be well described by sigmoid response-functions.
      Despite the limitations of only partial maximum inhibitions, this cell-based
      assay could be used to quantitate the suppressing ability of glucocorticoids
      (transrepression potency) on the expression of proinflammatory transcription
      factors caused by two different cytokines in parallel both in a detailed, full
      dose-response format as well as in a simpler single-dose format. Whereas
      inhibitory potencies obtained in the TNF assay correlated well with consensus
      glucocorticoid potencies (receptor-binding affinities, Kd, RBA, at the GR) for
      all compounds, the non-halogenated steroids (hydrocortisone, prednisolone, and
      loteprednol etabonate) were about an order of magnitude more potent than expected
      in the CD40 assay in this system. 

PMID- 24747771
TI  - 1alpha,25-dihydroxyvitamin D3 inhibits cell growth and NFkappaB signaling in
      tamoxifen-resistant breast cancer cells.
AB  - Resistance to antiestrogens is a major clinical problem in current breast cancer
      treatment and development of new treatment strategies for these tumors is highly
      prioritized. In this study, we have investigated the effects of 1alpha,25
      dihydroxyvitamin D3 on the proliferation of tamoxifen-resistant cells. Further,
      we have investigated on a molecular level the effects of vitamin D on NFkB
      signaling in tamoxifen-resistant breast cancer cells. Parental human breast
      cancer MCF-7 cells and four tamoxifen-resistant sublines have been used to
      investigate the effects of 1alpha,25-dihydroxyvitamin D3 on cell proliferation
      using a colorimetric method, gene expression using quantitative PCR, protein
      phosphorylation using Western blot analysis and cellular localization of proteins
      using immunofluorescence microscopy. We found that 1alpha,25-dihydroxyvitamin D3
      is able to strongly decrease the growth of both tamoxifen-sensitive and 
      resistant breast cancer cells and that this antiproliferative effect of 1alpha,25
      dihydroxyvitamin D3 might be mediated via inhibition of the NFkappaB pathway. We
      found that 1alpha,25-dihydroxyvitamin D3 stimulates the gene expression of IkB,
      an NFkappaB-inhibiting protein, and that cells pretreated with 1alpha,25
      dihydroxyvitamin D3 have a decreased sensitivity to TNFalpha stimulation.
      Further, we show that 1alpha,25-dihydroxyvitamin D3 treatment strongly decreases
      the TNFalpha-induced translocation of p65 into the nucleus. This manuscript
      reports novel findings regarding the effects of 1alpha,25-dihydroxyvitamin D3 on
      NFkappaB signaling in tamoxifen-resistant breast cancer cells and suggests that
      vitamin D might be interesting for further evaluation as a new strategy to treat
      antiestrogen-resistant breast cancers. 

PMID- 24747769
TI  - Cellular prostatic acid phosphatase, a PTEN-functional homologue in prostate
      epithelia, functions as a prostate-specific tumor suppressor.
AB  - The inactivation of tumor suppressor genes (TSGs) plays a vital role in the
      progression of human cancers. Nevertheless, those ubiquitous TSGs have been shown
      with limited roles in various stages of diverse carcinogenesis. Investigation on
      identifying unique TSG, especially for early stage of carcinogenesis, is
      imperative. As such, the search for organ-specific TSGs has emerged as a major
      strategy in cancer research. Prostate cancer (PCa) has the highest incidence in
      solid tumors in US males. Cellular prostatic acid phosphatase (cPAcP) is a
      prostate-specific differentiation antigen. Despite intensive studies over the
      past several decades on PAcP as a PCa biomarker, the role of cPAcP as a PCa
      specific tumor suppressor has only recently been emerged and validated. The
      mechanism underlying the pivotal role of cPAcP as a prostate-specific TSG is, in
      part, due to its function as a protein tyrosine phosphatase (PTP) as well as a
      phosphoinositide phosphatase (PIP), an apparent functional homologue to
      phosphatase and tensin homolog (PTEN) in PCa cells. This review is focused on
      discussing the function of this authentic prostate-specific tumor suppressor and
      the mechanism behind the loss of cPAcP expression leading to prostate
      carcinogenesis. We review other phosphatases' roles as TSGs which regulate
      oncogenic PI3K signaling in PCa and discuss the functional similarity between
      cPAcP and PTEN in prostate carcinogenesis. 

PMID- 24747772
TI  - Mucor hiemalis mediated 14alpha-hydroxylation on steroids: in vivo and in vitro
      investigations of 14alpha-hydroxylase activity.
AB  - Transformation of testosterone and progesterone into synthetically challenging
      14alpha-hydroxy derivatives was achieved by using fungal strain Mucor hiemalis.
      Prolonged incubation led to the formation of corresponding 6beta/7alpha,14alpha
      dihydroxy metabolites. The position and stereochemistry of newly introduced
      hydroxyl group was determined by detailed spectroscopic analyses. The time course
      experiment indicated that fungal strain initiated transformation by hydroxylation
      at 14alpha-position followed by at 6beta- or 7alpha-positions. Studies using cell
      free extracts suggest that the 14alpha-hydroxylase activity is NADPH dependent
      and belongs to the cytochrome P450 family. 

PMID- 24747774
TI  - Waiting and liminality: a phenomenon of spousal caregiving?
AB  - BACKGROUND: Waiting is an inevitable reality for cancer patients and their
      families. To date, a paucity of research has explored the meaning given to the
      emotional experience of waiting by spouses who provide care for cancer patients.
      OBJECTIVE: The purpose of this discussion article is to introduce readers to the
      concept of liminality as a mechanism to enhance understanding of the experience
      of waiting. Liminality may be thought of as the space betwixt and between.
      METHODS: The findings from a mixed-methods exploratory study that explored the
      experience of caregiving among spouses of hematopoietic stem cell transplant
      recipients are used to illustrate the experience of waiting. RESULTS: Waiting is
      discussed from the perspective of disembodied (clock/calendar time) and embodied
      (how waiting is lived) time. Liminality is introduced as a transitional and
      transformational phase where individuals create meaning out of the experience of
      waiting. CONCLUSION: Although waiting may be a universal experience, our
      understanding of the experience within the context of cancer remains a poorly
      understood phenomenon. Lost in disembodied time are the myriad and complex
      nuances of the individual experience. Conceptualizing waiting as embodied and
      liminal may offer an alternative perspective that may enhance our understanding
      of the experience particularly as it applies to caregivers of cancer patients.
      IMPLICATIONS FOR PRACTICE: By enhancing our understanding of the experience of
      spousal caregiving, in particular waiting, effective interventions may be
      developed to better support spousal caregivers across the cancer care continuum
      to reduce psychosocial distress.

PMID- 24747775
TI  - Prospects of genetic engineering for robust insect resistance.
AB  - Secondary plant metabolites are potentially of great value for providing robust
      resistance in plants against insect pests. Such metabolites often comprise small
      lipophilic molecules (SLMs), and can be similar also in terms of activity to
      currently used insecticides, for example, the pyrethroids, neonicotinoids and
      butenolides, which provide more effective pest management than the resistance
      traits exploited by breeding. Crop plants mostly lack the SLMs that provide their
      wild ancestors with resistance to pests. However, resistance traits based on the
      biosynthesis of SLMs present promising new opportunities for crop resistance to
      pests. Advances in genetic engineering of secondary metabolite pathways that
      produce insecticidal compounds and, more recently, SLMs involved in plant
      colonisation and development, for example, insect pheromones, offer specific new
      approaches but which are more demanding than the genetic engineering approaches
      adopted so far. In addition, nature also offers various opportunities for
      exploiting induction or priming for resistance metabolite generation. Thus, use
      of non-constitutively expressed resistance traits delivered via the seed is a
      more sustainable approach than previously achieved, and could underpin
      development of perennial arable crops protected by sentinel plant technologies. 

PMID- 24747773
TI  - Filoviruses in bats: current knowledge and future directions.
AB  - Filoviruses, including Ebolavirus and Marburgvirus, pose significant threats to
      public health and species conservation by causing hemorrhagic fever outbreaks
      with high mortality rates. Since the first outbreak in 1967, their origins,
      natural history, and ecology remained elusive until recent studies linked them
      through molecular, serological, and virological studies to bats. We review the
      ecology, epidemiology, and natural history of these systems, drawing on examples
      from other bat-borne zoonoses, and highlight key areas for future research. We
      compare and contrast results from ecological and virological studies of bats and
      filoviruses with those of other systems. We also highlight how advanced methods,
      such as more recent serological assays, can be interlinked with flexible
      statistical methods and experimental studies to inform the field studies
      necessary to understand filovirus persistence in wildlife populations and cross
      species transmission leading to outbreaks. We highlight the need for a more
      unified, global surveillance strategy for filoviruses in wildlife, and advocate
      for more integrated, multi-disciplinary approaches to understand dynamics in bat
      populations to ultimately mitigate or prevent potentially devastating disease
      outbreaks. 

PMID- 24747776
TI  - Characterization of reward and effort mechanisms in apathy.
AB  - Apathy is a common but poorly understood condition with a wide societal impact
      observed in several brain disorders as well as, to some extent, in the normal
      population. Hence the need for better characterization of the underlying
      mechanisms. The processes by which individuals decide to attribute physical
      effort to obtain rewards might be particularly relevant to relate to apathy
      traits. Here, we designed two paradigms to assess individual differences in
      physical effort production and effort-based decision-making and their relation to
      apathy in healthy people. Apathy scores were measured using a modified version of
      the Lille Apathy Rating Scale, suitable for use in a non-clinical population. In
      the first study, apathy scores were correlated with the degree to which stake
      (reward on offer) and difficulty level impacts on physical effort production.
      Individuals with relatively high apathy traits showed an increased modulation of
      effort while more motivated individuals generally exerted greater force across
      different levels of stake. To clarify the underlying mechanisms for this
      behavior, we designed a second task that allows independent titration of stake
      and effort levels for which subjects are willing to engage in an effortful
      response to obtain a reward. Our results suggest that apathy traits in the normal
      population are related to the way reward subjectively affects the estimation of
      effort costs, and more particularly manifest as decreased willingness to exert
      effort when rewards are small, or below threshold. The tasks we introduce here
      may provide useful tools to further investigate apathy in clinical populations.

PMID- 24747777
TI  - Variation in the degree of pectin methylesterification during the development of
      Baccharis dracunculifolia kidney-shaped gall.
AB  - Insect galls may be study models to test the distribution of pectins and
      arabinogalactan-proteins (AGPs) and their related functions during plant cell
      cycles. These molecules are herein histochemically and immunocitochemically
      investigated in the kidney-shaped gall induced by Baccharopelma dracunculifoliae
      (Psyllidae) on leaves of Baccharis dracunculifolia DC. (Asteraceae) on
      developmental basis. The homogalacturonans (HGAs) (labeled by JIM5) and the
      arabinans (labeled by LM6) were detected either in non-galled leaves or in young
      galls, and indicated stiffening of epidermal cell walls, which is an important
      step for cell redifferentiation. The labeling of HGAs by JIM7 changed from young
      to senescent stage, with an increase in the rigidity of cell walls, which is
      important for the acquaintance of the final gall shape and for the mechanical
      opening of the gall. The variation on the degree of HGAs during gall development
      indicated differential PMEs activity during gall development. The epitopes
      recognized by LM2 (AGP glycan) and LM5 (1-4-beta-D-galactans) had poor
      alterations from non-galled leaves towards gall maturation and senescence.
      Moreover, the dynamics of pectin and AGPs on two comparable mature kidney-shaped
      galls on B. dracunculifolia and on B. reticularia revealed specific
      peculiarities. Our results indicate that similar gall morphotypes in cogeneric
      host species may present distinct cell responses in the subcelular level, and
      also corroborate the functions proposed in literature for HGAs. 

PMID- 24747778
TI  - An assay for lateral line regeneration in adult zebrafish.
AB  - Due to the clinical importance of hearing and balance disorders in man, model
      organisms such as the zebrafish have been used to study lateral line development
      and regeneration. The zebrafish is particularly attractive for such studies
      because of its rapid development time and its high regenerative capacity. To
      date, zebrafish studies of lateral line regeneration have mainly utilized fish of
      the embryonic and larval stages because of the lower number of neuromasts at
      these stages. This has made quantitative analysis of lateral line
      regeneration/and or development easier in the earlier developmental stages.
      Because many zebrafish models of neurological and non-neurological diseases are
      studied in the adult fish and not in the embryo/larvae, we focused on developing
      a quantitative lateral line regenerative assay in adult zebrafish so that an
      assay was available that could be applied to current adult zebrafish disease
      models. Building on previous studies by Van Trump et al. that described
      procedures for ablation of hair cells in adult Mexican blind cave fish and
      zebrafish (Danio rerio), our assay was designed to allow quantitative comparison
      between control and experimental groups. This was accomplished by developing a
      regenerative neuromast standard curve based on the percent of neuromast
      reappearance over a 24 hr time period following gentamicin-induced necrosis of
      hair cells in a defined region of the lateral line. The assay was also designed
      to allow extension of the analysis to the individual hair cell level when a
      higher level of resolution is required.

PMID- 24747779
TI  - Layered materials: scaling up exfoliation.

PMID- 24747781
TI  - Optical Fano resonance of an individual semiconductor nanostructure.
AB  - Fano resonances with a characteristic asymmetric line shape can be observed in
      light scattering, transmission and reflection spectra of resonant optical
      systems. They result from interference between direct and indirect, resonance
      assisted pathways. In the nanophotonics field, Fano effects have been observed in
      a wide variety of systems, including metallic nanoparticle assemblies,
      metamaterials and photonic crystals. Their unique properties find extensive use
      in applications, including optical filtering, polarization selectors, sensing,
      lasers, modulators and nonlinear optics. We report on the observation of a Fano
      resonance in a single semiconductor nanostructure, opening up opportunities for
      their use in active photonic devices. We also show that Fano-resonant
      semiconductor nanostructures afford the intriguing opportunity to simultaneously
      measure the far-field scattering response and the near-field energy storage by
      extracting photogenerated charge. Together they can provide a complete
      experimental characterization of this type of resonance. 

PMID- 24747780
TI  - Scalable production of large quantities of defect-free few-layer graphene by
      shear exfoliation in liquids.
AB  - To progress from the laboratory to commercial applications, it will be necessary
      to develop industrially scalable methods to produce large quantities of defect
      free graphene. Here we show that high-shear mixing of graphite in suitable
      stabilizing liquids results in large-scale exfoliation to give dispersions of
      graphene nanosheets. X-ray photoelectron spectroscopy and Raman spectroscopy show
      the exfoliated flakes to be unoxidized and free of basal-plane defects. We have
      developed a simple model that shows exfoliation to occur once the local shear
      rate exceeds 10(4) s(-1). By fully characterizing the scaling behaviour of the
      graphene production rate, we show that exfoliation can be achieved in liquid
      volumes from hundreds of millilitres up to hundreds of litres and beyond. The
      graphene produced by this method performs well in applications from composites to
      conductive coatings. This method can be applied to exfoliate BN, MoS2 and a range
      of other layered crystals. 

PMID- 24747782
TI  - Auxetic nuclei in embryonic stem cells exiting pluripotency.
AB  - Embryonic stem cells (ESCs) self-renew in a state of naive pluripotency in which
      they are competent to generate all somatic cells. It has been hypothesized that,
      before irreversibly committing, ESCs pass through at least one metastable
      transition state. This transition would represent a gateway for differentiation
      and reprogramming of somatic cells. Here, we show that during the transition, the
      nuclei of ESCs are auxetic: they exhibit a cross-sectional expansion when
      stretched and a cross-sectional contraction when compressed, and their stiffness
      increases under compression. We also show that the auxetic phenotype of
      transition ESC nuclei is driven at least in part by global chromatin
      decondensation. Through the regulation of molecular turnover in the
      differentiating nucleus by external forces, auxeticity could be a key element in
      mechanotransduction. Our findings highlight the importance of nuclear structure
      in the regulation of differentiation and reprogramming. 

PMID- 24747783
TI  - Isolation of cellular lipid droplets: two purification techniques starting from
      yeast cells and human placentas.
AB  - Lipid droplets are dynamic organelles that can be found in most eukaryotic and
      certain prokaryotic cells. Structurally, the droplets consist of a core of
      neutral lipids surrounded by a phospholipid monolayer. One of the most useful
      techniques in determining the cellular roles of droplets has been proteomic
      identification of bound proteins, which can be isolated along with the droplets.
      Here, two methods are described to isolate lipid droplets and their bound
      proteins from two wide-ranging eukaryotes: fission yeast and human placental
      villous cells. Although both techniques have differences, the main method--
      density gradient centrifugation--is shared by both preparations. This shows the
      wide applicability of the presented droplet isolation techniques. In the first
      protocol, yeast cells are converted into spheroplasts by enzymatic digestion of
      their cell walls. The resulting spheroplasts are then gently lysed in a loose
      fitting homogenizer. Ficoll is added to the lysate to provide a density gradient,
      and the mixture is centrifuged three times. After the first spin, the lipid
      droplets are localized to the white-colored floating layer of the centrifuge
      tubes along with the endoplasmic reticulum (ER), the plasma membrane, and
      vacuoles. Two subsequent spins are used to remove these other three organelles.
      The result is a layer that has only droplets and bound proteins. In the second
      protocol, placental villous cells are isolated from human term placentas by
      enzymatic digestion with trypsin and DNase I. The cells are homogenized in a
      loose-fitting homogenizer. Low-speed and medium-speed centrifugation steps are
      used to remove unbroken cells, cellular debris, nuclei, and mitochondria. Sucrose
      is added to the homogenate to provide a density gradient and the mixture is
      centrifuged to separate the lipid droplets from the other cellular fractions. The
      purity of the lipid droplets in both protocols is confirmed by Western Blot
      analysis. The droplet fractions from both preps are suitable for subsequent
      proteomic and lipidomic analysis.

PMID- 24747784
TI  - Reversible protection of Cys-93(beta) by PEG alters the structural and functional
      properties of the PEGylated hemoglobin.
AB  - As a potential hemoglobin (Hb)-based oxygen carrier (HBOC), the PEGylated Hb has
      received much attention for its non-nephrotoxicity. However, PEGylation can
      adversely alter the structural and functional properties of Hb. The site of
      PEGylation is an important factor to determine the structure and function of the
      PEGylated Hb. Thus, protection of some sensitive residues of Hb from PEGylation
      is of great significance to develop the PEGylated Hb as HBOC. Here, Cys-93(beta)
      of Hb was conjugated with 20 kDa polyethylene glycol (PEG20K) through hydrazone
      and disulfide bonds. Then, the conjugate was modified with PEG5K succinimidyl
      carbonate (PEG5K-SC) using acylation chemistry, followed by removal of PEG20K Hb
      with hydrazone hydrolysis and disulfide reduction. Reversible conjugation of
      PEG20K at Cys-93(beta) can protect Lys-95(beta), Val-1(alpha) and Lys-16(alpha)
      of Hb from PEGylation with PEG5K-SC. The autoxidation rate, oxygen affinity,
      structural perturbation and tetramer instability of the PEGylated Hb were
      significantly decreased upon protection with PEG20K. The present study is
      expected to improve the efficacy of the PEGylated Hb as an oxygen therapeutic.

PMID- 24747785
TI  - Reply to "heart failure and breast cancer: emerging controversies regarding some
      cardioprotective strategies".

PMID- 24747786
TI  - Heart failure and breast cancer: emerging controversies regarding some
      cardioprotective strategies.

PMID- 24747787
TI  - Efficient and precise calculation of the b-matrix elements in diffusion-weighted
      imaging pulse sequences.
AB  - Precise NMR diffusion measurements require detailed knowledge of the cumulative
      dephasing effect caused by the numerous gradient pulses present in most NMR pulse
      sequences. This effect, which ultimately manifests itself as the diffusion
      related NMR signal attenuation, is usually described by the b-value or the b
      matrix in the case of multidirectional diffusion weighting, the latter being
      common in diffusion-weighted NMR imaging. Neglecting some of the gradient pulses
      introduces an error in the calculated diffusion coefficient reaching in some
      cases 100% of the expected value. Therefore, ensuring the b-matrix calculation
      includes all the known gradient pulses leads to significant error reduction.
      Calculation of the b-matrix for simple gradient waveforms is rather
      straightforward, yet it grows cumbersome when complexly shaped and/or numerous
      gradient pulses are introduced. Making three broad assumptions about the gradient
      pulse arrangement in a sequence results in an efficient framework for calculation
      of b-matrices as well providing some insight into optimal gradient pulse
      placement. The framework allows accounting for the diffusion-sensitising effect
      of complexly shaped gradient waveforms with modest computational time and power.
      This is achieved by using the b-matrix elements of the simple unmodified pulse
      sequence and minimising the integration of the complexly shaped gradient waveform
      in the modified sequence. Such re-evaluation of the b-matrix elements retains all
      the analytical relevance of the straightforward approach, yet at least halves the
      amount of symbolic integration required. The application of the framework is
      demonstrated with the evaluation of the expression describing the diffusion
      sensitizing effect, caused by different bipolar gradient pulse modules. 

PMID- 24747788
TI  - Suppression of spectral anomalies in SSFP-NMR signal by the Krylov Basis
      Diagonalization Method.
AB  - Krylov Basis Diagonalization Method (KBDM) is a numerical procedure used to fit
      time domain signals as a sum of exponentially damped sinusoids. In this work KBDM
      is used as an alternative spectral analysis tool, complimentary to Fourier
      transform. We report results obtained from (13)C Nuclear Magnetic Resonance (NMR)
      by Steady State Free Precession (SSFP) measurements in brucine, C23H26N2O4.
      Results lead to the conclusion that the KBDM can be successfully applied, mainly
      because it is not influenced by truncation or phase anomalies, as observed in the
      Fourier transform spectra. 

PMID- 24747789
TI  - Evolution of the hip fracture population: time to consider the future? A
      retrospective observational analysis.
AB  - OBJECTIVE: To examine how the population with fractured neck of femur has changed
      over the last decade and determine whether they have evolved to become a more
      physically and socially dependent cohort. DESIGN: Retrospective cohort study of
      prospectively collected Standardised Audit of Hip Fractures of Europe data
      entered on to an institutional hip fracture registry. PARTICIPANTS: 10 044
      consecutive hip fracture admissions (2000-2012). SETTING: A major trauma centre
      in the UK. RESULTS: There was a generalised increase in the number of admissions
      between 2000 (n=740) and 2012 (n=810). This increase was non-linear and best
      described by a quadratic curve. Assuming no change in the prevalence of hip
      fracture over the next 20 years, our hospital is projected to treat 871 cases in
      2020 and 925 in 2030. This represents an approximate year-on-year increase of
      just over 1%. There was an increase in the proportion of male admissions over the
      study period (2000: 174 of 740 admissions (23.5%); 2012: 249 of 810 admissions
      (30.7%)). This mirrored national census changes within the geographical area
      during the same period. During the study period there were significant increases
      in the numbers of patients admitted from their own home, the proportion of
      patients requiring assistance to mobilise, and the proportion of patients
      requiring help with basic activities of daily living (all p<0.001). There was
      also a twofold to fourfold increase in the proportion of patients admitted with a
      diagnosis of cardiovascular disease, renal disease, diabetes and polypharmacy
      (use of >4 prescribed medications; all p<0.001). CONCLUSIONS: The expanding hip
      fracture population has increasingly complex medical, social and rehabilitation
      care needs. This needs to be recognised so that appropriate healthcare strategies
      and service planning can be implemented. This epidemiological analysis allows
      projections of future service need in terms of patient numbers and dependency.

PMID- 24747790
TI  - Dietary fatty acids in the secondary prevention of coronary heart disease: a
      systematic review, meta-analysis and meta-regression.
AB  - OBJECTIVE: Previous systematic reviews were not restricted to either primary or
      secondary prevention trials, this study aimed to investigate the effects of
      reduced and/or modified fat diets and dietary fatty acids on all-cause mortality,
      cardiovascular mortality and cardiovascular events in participants with
      established coronary heart disease. DESIGN: Systematic review, meta-analysis and
      univariate/multivariate meta-regression. ELIGIBILITY AND CRITERIA FOR SELECTING
      STUDIES: Electronic searches for randomised controlled trials comparing
      reduced/modified fat diets versus control diets were performed in MEDLINE, EMBASE
      and the Cochrane Library. DATA EXTRACTION: Pooled effects were calculated using
      an inverse-variance random effect meta-analysis. Random effects univariate and
      multivariate meta-regressions were performed including changes in all types of
      dietary fatty acids. RESULTS: Overall, 12 studies enrolling 7150 participants
      were included in the present systematic review. No significant risk reduction
      could be observed considering all-cause mortality (relative risk (RR) 0.92,
      p=0.60; I(2)=59%) and cardiovascular mortality (RR 0.96, p=0.84; I(2)=69%),
      combined cardiovascular events (RR 0.85, p=0.30; I(2)=75%) and myocardial
      infarction (RR 0.76, p=0.13; I(2)=55%) comparing modified fat diets versus
      control diets. This results could be confirmed for the reduced fat versus control
      diets (RR 0.79, p=0.47; I(2)=0%), (RR 0.93, p=0.66; I(2)=0%), (RR 0.93, p=0.71;
      I(2)=57%) and (RR 1.18, p=0.26; I(2)=18%). The multivariate and univariate model
      showed no significant associations between the independent variables and the
      changes from saturated fat, monounsaturated fat, polyunsaturated fat and linoleic
      acid. Sensitivity analyses did not reveal a significant risk reduction for any
      outcome parameter when polyunsaturated fat was increased in exchange for
      saturated fat. CONCLUSIONS: The present systematic review provides no evidence
      (moderate quality evidence) for the beneficial effects of reduced/modified fat
      diets in the secondary prevention of coronary heart disease. Recommending higher
      intakes of polyunsaturated fatty acids in replacement of saturated fatty acids
      was not associated with risk reduction.

PMID- 24747791
TI  - Controlling methicillin-resistant Staphylococcus aureus (MRSA) in a hospital and
      the role of hydrogen peroxide decontamination: an interrupted time series
      analysis.
AB  - OBJECTIVES: The impact of surface disinfection versus detergent cleaning on
      healthcare associated infection rates remains unresolved. We aimed to evaluate
      the efficacy of hydrogen peroxide (HP) decontamination against methicillin
      resistant Staphylococcus aureus (MRSA). DESIGN: Single centred retrospective
      before and after study design. SETTING: Launceston General Hospital, Tasmania,
      Australia. PARTICIPANTS: Patients with MRSA infection or colonisation.
      INTERVENTIONS: Rooms occupied by patients with MRSA infection or colonisation
      were cleaned following discharge with either detergent or HP. MAIN OUTCOME
      MEASURES: MRSA room contamination following cleaning; new MRSA acquisition in
      patients. RESULTS: Over 3600 discharge cleans were completed, with more than 32
      600 environmental swabs processed. MRSA was isolated from 24.7% rooms following
      detergent cleaning and from 18.8% of rooms after HP (p<0.001). The incidence of
      MRSA acquisition reduced from 9.0 to 5.3 per 10 000 patient days in detergent and
      disinfectant arms, respectively (p<0.001). CONCLUSIONS: Use of HP disinfection
      led to a decrease in residual MRSA contamination in patient rooms compared with
      detergent. It may also have encouraged the reduction in patient MRSA acquisition
      despite several confounders including staff feedback on terminal cleaning,
      additional MRSA screening and quicker laboratory methods. Infection control is
      best served by concurrent interventions targeting both the patient and healthcare
      environment.

PMID- 24747792
TI  - Key health outcomes for children and young people with neurodisability:
      qualitative research with young people and parents.
AB  - OBJECTIVES: To identify key health outcomes, beyond morbidity and mortality,
      regarded as important in children and young people with neurodisability, and
      their parents. DESIGN: Qualitative research incorporating a thematic analysis of
      the data supported by the Framework Approach; the International Classification of
      Functioning, Disability and Health (ICF) provided a theoretical foundation.
      SETTING: The study was conducted in community settings. PARTICIPANTS:
      Participants were 54 children and young people with neurodisability: 50
      participated in focus groups, and 4 in interviews; 53 parents participated: 47 in
      focus groups and 6 in interviews. Children/young people and parents were
      recruited through different networks, and were not related. RESULTS:
      Children/young people and parents viewed health outcomes as inter-related.
      Achievement in some outcomes appeared valued to the extent that it enabled or
      supported more valued domains of health. Health outcomes prioritised by both
      young people and parents were: communication, mobility, pain, self-care,
      temperament, interpersonal relationships and interactions, community and social
      life, emotional well-being and gaining independence/future aspirations. Parents
      also highlighted their child's sleep, behaviour and/or safety. CONCLUSIONS: Those
      responsible for health services for children/young people with neurodisability
      should take account of the aspects of health identified by families. The aspects
      of health identified in this study provide a basis for selecting appropriate
      health indicators and outcome measures.

PMID- 24747793
TI  - The potential role of NT-proBNP in screening for and predicting prognosis in
      heart failure: a survival analysis.
AB  - OBJECTIVE: To determine the potential role of N-terminal pro-B-type natriuretic
      peptide (NT-proBNP) in screening for and predicting prognosis in heart failure by
      examining diagnosis and survival of patients with a raised NT-proBNP at
      screening. DESIGN: Survival analysis. SETTING: Prospective substudy of the
      Echocardiographic Heart of England Screening study (ECHOES) to investigate 10
      year survival in participants with an NT-proBNP level at baseline. PARTICIPANTS:
      594 participants took part in the substudy. Records of all participants in the
      ECHOES cohort were flagged during the screening phase which ended on 25 February
      1999. All deaths until 25 February 2009 were coded. OUTCOME MEASURES: Logistic
      regression was used to examine whether NT-proBNP is useful in predicting heart
      failure at screening after adjustment for age, sex and cohort. Kaplan-Meier
      curves and log rank tests were used to compare survival times of participants
      according to NT-proBNP level. Cox regression was carried out to assess the
      prognostic effect of NT-proBNP after allowing for significant covariates and
      receiver operator curves were used to determine test reliability. RESULTS: The
      risk of heart failure increased almost 18-fold when NT-proBNP was 150 pg/mL or
      above (adjusted OR=17.7, 95% CI 4.9 to 63.5). 10-year survival in the general
      population cohort was 61% (95% CI 48% to 71%) for those with NT-proBNP >=150
      pg/mL and 89% (95% CI 84% to 92%) for those below the cut-off at the time of the
      initial study. After adjustment for age, sex and risk factors for heart failure,
      NT-proBNP level >=150 pg/mL was associated with a 58% increase in the risk of
      death within 10 years (adjusted HR=1.58, 95% CI 1.09 to 2.30). CONCLUSIONS:
      Raised NT-proBNP levels, when screening the general population, are predictive of
      a diagnosis of heart failure (at a lower threshold than guidelines for diagnosing
      symptomatic patients) and also predicted reduced survival at 10 years.

PMID- 24747794
TI  - Awareness and enforcement of guidelines for publishing industry-sponsored medical
      research among publication professionals: the Global Publication Survey.
AB  - OBJECTIVE: To gather information about current practices and implementation of
      publication guidelines among publication professionals working in or for the
      pharmaceutical industry. DESIGN/SETTING: Web-based survey publicised via email
      and social media to members of the International Society for Medical Publication
      Professionals (ISMPP) and other organisations from November 2012 to February
      2013. PARTICIPANTS: 469 individuals involved in publishing industry-sponsored
      research in peer-reviewed journals, mainly working in pharmaceutical or device
      companies ('industry', n=144), communication agencies ('agency', n=238), contract
      research organisations (CRO, n=15) or as freelancers (n=34). Most respondents
      (78%) had worked on medical publications for >=5 years and 62% had a PhD/MD.
      RESULTS: Over 90% of industry, agency and CRO respondents routinely refer to Good
      Publication Practice (GPP2) and the International Committee of Medical Journal
      Editors' Uniform Requirements. Most respondents (78% industry, 79% agency)
      received mandatory training on ethical publication practices. Over 90% of
      respondents' companies had publication guidelines or policies and required
      medical writing support to be acknowledged in publications (96% industry, 99%
      agency). Many industry respondents used publication management tools to monitor
      compliance with company guidelines and about half (46%) stated that their company
      had formal publication audits. Fewer agencies audited adherence to guidelines but
      20% of agency respondents reported audits of employees and 6% audits of
      freelancers. Of concern, 37% of agency respondents reported requests from authors
      or sponsors that they believed were unethical, although 93% of these requests
      were withdrawn after respondents explained the need for compliance with
      guidelines. Most respondents' departments (63% industry, 58% agency, 60% CRO) had
      been involved in publishing studies with negative or inconclusive results.
      CONCLUSIONS: Within this sample, most publication professionals working in or for
      industry were aware of, and applying, major publication guidelines. However, the
      survey also identified specific areas where education and promotion of guidelines
      are needed to ensure ethical publication practices.

PMID- 24747795
TI  - Simulating the impact of changing trends in smoking and obesity on productivity
      of an industrial population: an observational study.
AB  - OBJECTIVE: To estimate the impact of trends in smoking and obesity prevalence on
      productivity loss among petrochemical employees from 1980 to 2009. METHODS:
      Smoking and obesity informations were collected during company physical
      examinations. Productivity loss was calculated as differential workdays lost
      between smokers and non-smokers, and obese and normal-weight employees. RESULTS:
      During 1980-2009, smoking prevalence decreased from 32% to 17%, while obesity
      prevalence increased from 14% to 42%. In 1982, lost productivity from obesity was
      an estimated 43 days/100 employees, and for smoking, 65 days/100 employees, but
      by 1987, workdays lost due to obesity exceeded that attributable to smoking. In
      2007, workdays lost from obesity were 3.7 times higher than for smoking.
      CONCLUSIONS: Owing to the increasing trend in obesity, the productivity impact on
      employers from obesity will continue to rise without effective measures
      supporting employee efforts to achieve healthy weight through sustainable
      lifestyle changes.

PMID- 24747796
TI  - Critical role of smoking and household dampness during childhood for adult phlegm
      and cough: a research example from a prospective cohort study in Great Britain.
AB  - OBJECTIVE: To examine independent associations between childhood exposures to
      smoking and household dampness, and phlegm and cough in adulthood. DESIGN: A
      prospective cohort study. PARTICIPANTS: 7320 of the British cohort who were born
      during 1 week in 1970 and had complete data for childhood and adult information.
      MAIN OUTCOME MEASURES: Experiences of phlegm and coughing over the previous 3
      months were assessed using questions from the Medical Research Council (MRC)
      Questionnaire on respiratory symptoms when the cohort participants were 29 years
      of age. 4 response patterns (no symptoms, phlegm only, cough only, both symptoms
      present) were created based on the responses to these questions. RESULTS:
      Childhood smoking and exposure to marked household dampness at age 10 were
      associated with phlegm (childhood smoking: relative risk ratio (RRR)=1.45, 95% CI
      1.02 to 2.05; dampness: RRR=2.05, 95% CI 1.07 to 3.91) and co-occurring cough and
      phlegm (childhood smoking: RRR=1.35. 95% CI 1.08 to 1.67; dampness: RRR=2.73, 95%
      CI 1.88 to 3.99), while exposure to two or more adult smokers in the household
      was associated with cough-related symptoms (cough only: RRR=1.28, 95% CI 1.04 to
      1.58; phlegm and cough: RRR=1.32, 95% CI 1.06 to 1.64). These associations were
      independent from adult smoking, childhood phlegm and cough, early social
      background and sex. Current smoking at age 29 contributed to all symptom
      patterns; however, a substantial association between household dampness and co
      occurring phlegm and cough suggest long-term detrimental effects of childhood
      environmental exposures. CONCLUSIONS: Our findings give support to current public
      health interventions for adult smoking and raise concerns about the long-term
      effects of a damp home environment on the respiratory health of children.

PMID- 24747797
TI  - Clinical features of isolated gestational proteinuria progressing to pre
      eclampsia: retrospective observational study.
AB  - OBJECTIVES: Some women with isolated gestational proteinuria (IGP) later develop
      hypertension and are diagnosed with pre-eclampsia (PE). This study was performed
      to determine whether clinical features of such proteinuria preceding PE (P-PE)
      differ from those of other PE (O-PE). DESIGN: Retrospective observational study
      after approval of the institutional review board of ethics. SETTING: A single
      university hospital. Proteinuria was defined as a protein-to-creatinine ratio
      (mg/mg; P/Cr) of >=0.27 in the spot urine specimen. IGP was defined as
      proteinuria in the absence of hypertension. P-PE was defined as PE in which
      proteinuria preceded hypertension by more than 2 days. PARTICIPANTS: All of 10
      and 18 consecutive women with P-PE and O-PE, respectively, who gave birth between
      January 2008 and August 2013. RESULTS: Proteinuria appeared earlier (at 30.2+/
      3.0 vs 35.3+/-4.3 weeks, p=0.001), the P/Cr level was greater at birth (7.28+/
      2.14 vs 3.19+/-2.49, p<0.001), net maternal weight gain during the last antenatal
      1 week was greater (3.1+/-1.8 vs 1.3+/-1.7 kg, p=0.023) and length of pregnancy
      was shorter (32.5+/-1.9 vs 36.1+/-3.6 weeks, p=0.001) in women with P-PE than in
      O-PE. The duration of IGP was 10.0+/-5.9 days (range 3-20), and the time interval
      until delivery after diagnosis of PE was 6.1+/-8.2 days (range 0-23) in 10 women
      with P-PE. The P/Cr levels at birth were significantly inversely correlated with
      the antenatal lowest antithrombin activity and fibrinogen levels among the 28
      women with PE. CONCLUSIONS: Women with P-PE were likely to exhibit greater
      proteinuria in the urine, greater water retention in the interstitial space and
      more enhanced coagulation-fibrinolysis, thus suggesting that they may constitute
      a more severe form of PE than women with O-PE do.

PMID- 24747798
TI  - Safety and efficacy of boceprevir/peginterferon/ribavirin for HCV G1 compensated
      cirrhotics: meta-analysis of 5 trials.
AB  - BACKGROUND & AIMS: HCV-infected cirrhotics may urgently need therapy but are
      often under-represented in clinical trials resulting in limited data to guide
      their management. We performed a meta-analysis of well-compensated cirrhotic
      patients from five Phase 3 trials. METHODS: Patients received P/R
      (peginterferon/ribavirin; 4 weeks) followed by BOC (boceprevir)/P/R or P/R for
      24, 32, or 44 weeks. Sustained virologic response (SVR) rates were calculated by
      Metavir score. Multivariate logistic regression (MLR) models identified baseline
      and on-treatment predictors of SVR. Safety was evaluated by adverse-event (AE)
      reporting and laboratory monitoring. RESULTS: Pooled meta-estimates for SVR rates
      (95% confidence interval) in 212 F4 (cirrhotic) patients were 55% (43, 66) with
      BOC/P/R vs.17% (0, 41) with P/R. MLR identified 4 predictors of SVR in F3/F4
      patients: undetectable HCV-RNA at treatment week (TW) 8; ? 1 log10 decline in HCV
      RNA from baseline at TW4; male; and baseline HCV-RNA ? 800,000 IU/ml. SVR rate
      was 89% (65/73) in F4 patients who were HCV-RNA undetectable at TW8. No F3 (0/5)
      or F4 (0/17) patients with <3 log10 decline and detectable HCV-RNA at TW8
      achieved SVR. Anemia and diarrhea occurred more frequently in cirrhotic than non
      cirrhotic patients. Serious AEs, discontinuations due to an AE, interventions to
      manage anemia, infections, and thrombocytopenia occurred more frequently in
      cirrhotics with BOC/P/R than P/R. Potential hepatic decompensation and/or sepsis
      were identified in 2 P/R and 3 BOC/P/R recipients. CONCLUSIONS: BOC/P/R appears
      to have a generally favorable benefit-risk profile in compensated cirrhotic
      patients. SVR rates were particularly high in cirrhotic patients with
      undetectable HCV-RNA at TW8.

PMID- 24747799
TI  - The anabolic effect of plasma-mediated ablation on the intervertebral disc:
      stimulation of proteoglycan and interleukin-8 production.
AB  - BACKGROUND CONTEXT: Plasma-mediated radiofrequency-based ablation (coblation) is
      an electrosurgical technique currently used for tissue removal in a wide range of
      surgical applications, including lumbar microdiscectomy. In vitro and in vivo
      studies have shown the technique to alter the expression of inflammatory
      cytokines in the disc, increasing the levels of interleukin-8 (IL-8), which may
      promote maturation and remodeling of the disc matrix. PURPOSE: To better
      understand the effect of coblation treatment, this study characterizes the
      temporal and spatial pattern of healing after stab injury to the rabbit
      intervertebral disc, with and without plasma-mediated radiofrequency treatment.
      PATIENT SAMPLE: A total of 23 New Zealand white rabbits. STUDY DESIGN: Annular
      and nuclear stab injuries. OUTCOME MEASURES: Sandwich enzyme-linked immunosorbent
      assay evaluated the concentrations of cytokines tumor necrosis factor-alpha, IL
      1beta, and IL-8. Histopathologic evaluations were performed on whole discs and
      end plates. Tissue sections were stained with Safranin-O to evaluate nucleus
      pulposus and annulus fibrosus proteoglycan content and with Alcian blue for
      extracellular proteoglycan content. Intradiscal leakage pressure was evaluated by
      injecting methylene blue dye into the nucleus. METHODS: Animals underwent annular
      and nuclear stab injuries on three consecutive lumbar discs (L2-L3 to L4-L5). The
      three levels were randomly assigned into one of the three groups for treatment
      with a plasma-mediated radiofrequency ablation device (TOPAZ; ArthroCare Corp.,
      Austin, TX, USA): active treatment of the nucleus only (SN); active treatment of
      both nucleus and annulus (SNA); sham treatment. Unstabbed/untreated discs from L5
      L6 (n=5) served as normal controls. Animals were euthanized at 4, 8, and 28 days
      postsurgery. RESULTS: Tumor necrosis factor-alpha was detected in sham discs at 4
      and 8 days, but not in coblation groups (SN or SNA); IL-1beta was below detection
      in all three treatment groups. Interleukin-8 levels increased in all treatment
      groups at 4 and 8 days compared with normal control, peaking at 4th day for sham
      and SN groups and 8th day (p>.3) for the SNA group (a 2.5-fold increase).
      Pressure measurements revealed higher leakage in the SN group, but no
      statistically significant differences. Histopathology showed higher proteoglycan
      production by 28 days in the SNA and SN groups compared with sham. All three
      treatment groups showed ruptured annular fibers from the stab injury, but
      maintained the overall architecture. Remnants of notochordal tissue within the
      nucleus were evident in all treatment groups at 4 and 8 days, but were only found
      in sham group by 28 days. At this time, unlike the normal or sham controls, the
      nucleus of SN and SNA discs had fibrocartilaginous tissue with chondrocyte-like
      cells. Significant differences in the disc architecture grade were only noted
      when comparing normal controls with other groups by 28 days (p<.001).
      CONCLUSIONS: Plasma-mediated radiofrequency ablation appears to have an anabolic
      effect on disc cells, stimulating proteoglycan and IL-8 production and
      maintaining annulus architecture. Coblation treatment appears to reduce cellular
      response to proinflammatory stimuli and restore overall disc architecture that
      may prove beneficial in a number of degenerative disc paradigms. Further studies
      are encouraged to investigate the therapeutic effect of the technique.

PMID- 24747800
TI  - Immediate differentiation of neuronal cells from stem/progenitor-like cells in
      the avian iris tissues.
AB  - A simple culture method that was recently developed in our laboratory was applied
      to the chick iris tissues to characterize neural stem/progenitor-like cells. Iris
      tissue is a non-neuronal tissue and does not contain any neuronal cells. In the
      present study we isolated iris tissues from chick embryos just prior to hatching.
      The isolated iris pigmented epithelium (IPE) or the stroma was embedded in
      Matrigel and cultured in Dulbecco's MEM supplemented with either fetal bovine
      serum or the synthetic serum replacement solution B27. Within 24 h of culture,
      elongated cells with long processes extended out from the explants of both
      tissues and were positively stained for various neuronal markers such as
      transitin, Tuj-1 and acetylated tubulin. After a longer culture period, cells
      positive for photoreceptor markers like rhodopsin, iodopsin and visinin were
      found, suggesting that the iris tissues contain retinal stem/progenitor-like
      cells. Several growth factors were examined to determine their effects on
      neuronal differentiation. EGF was shown to dramatically enhance neuronal cell
      differentiation, particularly the elongation of neuronal fibers. The addition of
      exogenous FGF2, however, did not show any positive effects on neuronal
      differentiation, although FGF signaling inhibitor, SU5402, suppressed neuronal
      differentiation. The results show that neuronal stem/progenitor-like cells can
      differentiate into neuronal cells immediately after they are transferred into an
      appropriate environment. This process did not require any exogenous factors,
      suggesting that neural stem/progenitor-like cells are simply suppressed from
      neuronal differentiation within the tissue, and isolation from the tissue
      releases the cells from the suppression mechanism.

PMID- 24747801
TI  - Reaction time and incident cancer: 25 years of follow-up of study members in the
      UK Health and Lifestyle Survey.
AB  - OBJECTIVES: To investigate the association of reaction time with cancer
      incidence. METHODS: 6900 individuals aged 18 to 94 years who participated in the
      UK Health and Lifestyle Survey in 1984/1985 and were followed for a cancer
      registration for 25 years. RESULTS: Disease surveillance gave rise to 1015 cancer
      events from all sites. In general, there was essentially no clear pattern of
      association for either simple or choice reaction time with cancer of all sites
      combined, nor specific malignancies. However, selected associations were found
      for lung cancer, colorectal cancer and skin cancer. CONCLUSIONS: In the present
      study, reaction time and its components were not generally related to cancer
      risk.

PMID- 24747802
TI  - Increased p16 DNA methylation in mouse thymic lymphoma induced by irradiation.
AB  - DNA methylation is an important part of epigenetics. In this study, we examined
      the methylation state of two CpG islands in the promoter of the p16 gene in
      radiation-induced thymic lymphoma samples. The mRNA and protein levels of P16
      were significantly reduced in radiation-induced thymic lymphoma tissue samples.
      Twenty-three CpG sites of the CpG islands in the p16 promoter region were
      detected, and the methylation percentages of -71, -63, -239, -29, -38, -40, -23,
      46 CpG sites were significantly higher in radiation-induced thymic lymphoma
      tissue samples than those in matched non-irradiated thymus tissue samples. This
      study provides new evidence for the methylation state of p16 in the radiation
      induced thymic lymphoma samples, which suggests that the methylation of these CpG
      sites in the p16 promoter may reduce its expression in the thymic lymphoma after
      irradiation. 

PMID- 24747803
TI  - Neuroglobin - a potential biological marker of retinal damage induced by LED
      light.
AB  - Neuroglobin (NGB), a protein highly expressed in the retina, has been shown to be
      up-regulated to protect neurons from hypoxic and ischemic injuries. It exhibits
      neuroprotective functions and plays an important role in the survival of neurons.
      Recent studies show that light-emitting diode (LED) white light emitted
      significant amounts of blue light (short-wavelength), which may be harmful to
      retinal cells, but the studies about biomarkers for evaluating the damage from
      LED white light are still insufficient. In our study, we found that NGB levels in
      the retina showed a twofold increase and peaked at 1h after a 1-h exposure to
      blue light (453 nm) which did not cause damage to the retina. However, retinal
      damage was observed after 2h of blue-light irradiation, which induced an
      approximate sevenfold increase of NGB levels as confirmed by Western blot and RT
      PCR analysis. Immunofluorescence study demonstrated that NGB was predominantly up
      regulated in the ganglion cell layer (GCL), plexiform layer (PL) and
      photoreceptor layer (PRL). We also examined Ngb mRNA and protein expression in
      the damaged retina induced by light of other wavelengths given equal photon
      fluxes. The LED red light (625 nm), green light (527 nm) and blue light (453 nm)
      increased the expression of NGB and caused TdT-mediated dUTP nick-end labeling
      positive cells, especially in the blue-light group. In addition, a negative
      correlation between NGB and rhodopsin was observed. These findings suggested that
      there was a correlation between NGB expression and the severity of the retinal
      damage, indicating NGB's potential function as a biological marker of retinal
      damage induced by LED light.

PMID- 24747804
TI  - Generation and characterization of gsualpha:EGFP transgenic zebrafish for
      evaluating endocrine-disrupting effects.
AB  - The glycoprotein subunit alpha (gsualpha) gene encodes the shared alpha subunit
      of the three pituitary heterodimeric glycoprotein hormones: follicle-stimulating
      hormone beta (Fshbeta), luteinizing hormone beta (Lhbeta) and thyroid stimulating
      hormone beta (Tshbeta). In our current study, we identified and characterized the
      promoter region of zebrafish gsualpha and generated a stable gsualpha:EGFP
      transgenic line, which recapitulated the endogenous gsualpha expression in the
      early developing pituitary gland. A relatively conserved regulatory element set
      is presented in the promoter regions of zebrafish and three other known mammalian
      gsualpha promoters. Our results also demonstrated that the expression patterns of
      the gsualpha:EGFP transgene were all identical to those expression patterns of
      the endogenous gsualpha expression in the pituitary tissue when our transgenic
      fish were treated with various endocrine chemicals, including forskolin (FSK),
      SP600125, trichostatin A (TSA), KClO4, dexamethasone (Dex), beta-estradiol and
      progesterone. Thus, this gsualpha:EGFP transgenic fish reporter line provides
      another valuable tool for investigating the lineage development of gsualpha
      expressing gonadotrophins and the coordinated regulation of various glycoprotein
      hormone subunit genes. These reporter fish can serve as a novel platform to
      perform screenings of endocrine-disrupting chemicals (EDCs) in vivo as well. 

PMID- 24747805
TI  - Pulmonary function responses to ozone in smokers with a limited smoking history.
AB  - In non-smokers, ozone (O3) inhalation causes decreases in forced expiratory
      volume (FEV1) and dead space (VD) and increases the slope of the alveolar plateau
      (SN). We previously described a population of smokers with a limited smoking
      history that had enhanced responsiveness to brief O3 boluses and aimed to
      determine if responsiveness to continuous exposure was also enhanced. Thirty
      smokers (19M, 11F, 24+/-4 years, 6+/-4 total years smoking,4+/-2 packs/week) and
      30 non-smokers (17M, 13F, 25+/-6 years) exercised for 1h on a cycle ergometer
      while breathing 0.30ppm O3. Smokers and non-smokers were equally responsive in
      terms of FEV1 (-9.5+/-1.8% vs -8.7+/-1.9%). Smokers alone were responsive in
      terms of VD (-6.1+/-1.2%) and SN (9.1+/-3.4%). There was no difference in total
      delivered dose. Dead space ventilation (VD/VT) was not initially different
      between the two groups, but increased in the non-smokers (16.4+/-2.8%) during the
      exposure, suggesting that the inhaled dose may be distributed more peripherally
      in smokers. We also conclude that these cigarette smokers retain their airway
      responsiveness to O3 and, uniquely, experience changes in VD that lead to
      heterogeneity in airway morphometry and an increase in SN.

PMID- 24747806
TI  - Efficacy of detergent and water versus bleach for disinfection of direct contact
      ophthalmic lenses.
AB  - PURPOSE: Although manufacturers recommend cleaning ophthalmic lenses with
      detergent and water and then with a specific disinfectant, disinfectants are
      rarely used in ophthalmic practices. The aim of this pilot study was to evaluate
      the efficacy of detergent and water versus that of bleach, a recommended
      disinfectant, to eliminate common ocular bacteria and viruses from ophthalmic
      lenses. METHODS: Three bacterial strains (Staphylococcus epidermidis,
      Corynebacterium straitum, and methicillin-resistant Staphylococcus aureus and 2
      viral strains (adenovirus and herpes simplex virus [HSV] type-1) were
      individually inoculated onto 20 gonioscopy and laser lenses. The lenses were
      washed with detergent and water and then disinfected with 10% bleach. All the
      lenses were cultured after inoculation, after washing with detergent and water,
      and after disinfecting with the bleach. Bacterial cultures in thioglycollate
      broth were observed for 3 weeks, and viral cultures were observed for 2 weeks.
      The presence of viruses was also detected by multiplex polymerase chain reaction
      (PCR). RESULTS: All 20 lenses inoculated with S. epidermidis, C. straitum,
      adenovirus, and HSV-1 showed growth after inoculation but no growth after washing
      with detergent/water and after disinfecting with the bleach. All lenses showed
      positive HSV and adenovirus PCR results after inoculation and negative PCR
      results after washing with detergent/water and after disinfecting with bleach.
      All methicillin-resistant S. aureus-contaminated lenses showed growth after
      inoculation and no growth after washing with detergent and water. However, 1 lens
      showed positive growth after disinfecting with bleach. CONCLUSIONS: Cleaning with
      detergent and water seemed to effectively eliminate bacteria and viruses from the
      surface of contaminated ophthalmic lenses. Further studies are warranted to
      design practical disinfection protocols that minimize lens damage.

PMID- 24747807
TI  - Time perspective as a determinant of smoking cessation in four countries: Direct
      and mediated effects from the International Tobacco Control (ITC) 4-Country
      Surveys.
AB  - BACKGROUND: Future oriented time perspective predicts a number of important
      health behaviors and outcomes, including smoking cessation. However, it is not
      known how future orientation exerts its effects on such outcomes, and no large
      scale cross-national studies have examined the question prospectively. The aim of
      the current investigation was to examine the relationship between time
      perspective and success in smoking cessation, and social cognitive mediators of
      the association. METHODS: The ITC-4 is a multi-wave, four country survey
      (Australia, Canada, United States, United Kingdom) of current smokers (N=9772);
      the survey includes baseline measurements of time perspective, intentions, quit
      attempts, and self-reported quit status at follow-up over 8 years. We examined
      the predictive power of time perspective for smoking cessation, as mediated
      through strength of quit intentions and prior history of quit attempts. RESULTS:
      Findings indicated that those smokers with a stronger future orientation at
      baseline were more likely to have successfully quit at follow-up. This effect was
      partially explained by intention-mediated effects of future orientation on quit
      attempts. CONCLUSIONS: Future orientation predicts smoking cessation across four
      English-speaking countries; the cessation-facilitating effects of future
      orientation may be primarily due to future oriented individuals' motivated and
      sustained involvement in the quit cycle over time.

PMID- 24747808
TI  - Practical animal breeding as the key to an integrated view of genetics, eugenics
      and evolutionary theory: Arend L. Hagedoorn (1885-1953).
AB  - In the history of genetics Arend Hagedoorn (1885-1953) is mainly known for the
      'Hagedoorn effect', which states that part of the changes in variability that
      populations undergo over time are due to chance effects. Leaving this
      contribution aside, Hagedoorn's work has received scarcely any attention from
      historians. This is mainly due to the fact that Hagedoorn was an expert in animal
      breeding, a field that historians have only recently begun to explore. His work
      provides an example of how a prominent geneticist envisaged animal breeding to be
      reformed by the new science of heredity. Hagedoorn, a pupil of Hugo de Vries,
      tried to integrate his insights as a Mendelian geneticist and an animal breeding
      expert in a unified view of heredity, eugenics and evolution. In this paper I aim
      to elucidate how these fields were connected in Hagedoorn's work.

PMID- 24747809
TI  - Efficacy of multi-functional liposomes containing daunorubicin and emetine for
      treatment of acute myeloid leukaemia.
AB  - Despite recent advances in chemotherapy against acute myeloid leukaemia (AML),
      the disease still has high mortality, particularly for patients who tolerate
      extensive chemotherapy poorly. Nano-formulations have potential to minimise the
      adverse effects of chemotherapy. We present here a liposomal formulation
      encapsulating both the anthracycline daunorubicin (DNR) and emetine (Eme) for
      enhanced cytotoxic effect against AML cells. Eme could be loaded into the
      PEGylated liposomes together with DNR by the acid precipitation principle, with a
      loading efficiency of Eme at about 50% of that of DNR. The liposome surface was
      modified with folate to enhance drug loading into cells, giving higher cytotoxic
      activity. Both intracellular drug loading and cytotoxic activity could be further
      increased by anti-folate treatment of AML cells with methotrexate (MTX). The
      combination of DNR and Eme also increased drug loading in MTX-treated cells
      compared to DNR alone. Liposomes with both DNR and Eme were particularly
      efficient against AMLs with deficient p53. In conclusion, we have produced a
      multi-functional liposomal anti-leukaemic drug formulation designed to overcome
      some of the problems in anthracycline chemotherapy: (1) Combination of DNR and
      Eme to diminish drug resistance. (2) Using PEGylated stealth liposomes to
      minimise adverse side-effects. (3) Molecules on the liposomal surface target
      proteins on AML-cells ensure selectivity, which was enhanced by priming the
      leukaemia cells with MTX. 

PMID- 24747810
TI  - Characterization of protein-adjuvant coencapsulation in microparticles for
      vaccine delivery.
AB  - Protein antigens encapsulated as vaccines in poly[(rac-lactide)-co-glycolide]
      (PLGA) microparticle carriers can induce immune responses. The intensity and
      directions of this response can be controlled by coloading the microparticles
      with immunomodulatory adjuvants, e.g., muramyl dipeptide (MDP) as adjuvant
      combined with ovalbumin (Ova) as protein antigen. In this study, methodologies
      for an individual quantification of both encapsulated substances should be
      reported, which comprise (i) a separation process to isolate and determine MDP as
      intact molecule and (ii) a simultaneous degradation of both analytes with
      subsequent specific quantification of Ova fragments. It was shown that coloading
      of both substances resulted in a substantially reduced encapsulation efficiency
      of MDP. This illustrates that correct conclusions on dose-response relationships
      in future vaccination studies can only be drawn, if a selective method for
      adjuvant and protein quantification will be applied. 

PMID- 24747811
TI  - Nucleoside triphosphates--from synthesis to biochemical characterization.
AB  - The traditional strategy for the introduction of chemical functionalities is the
      use of solid-phase synthesis by appending suitably modified phosphoramidite
      precursors to the nascent chain. However, the conditions used during the
      synthesis and the restriction to rather short sequences hamper the applicability
      of this methodology. On the other hand, modified nucleoside triphosphates are
      activated building blocks that have been employed for the mild introduction of
      numerous functional groups into nucleic acids, a strategy that paves the way for
      the use of modified nucleic acids in a wide-ranging palette of practical
      applications such as functional tagging and generation of ribozymes and DNAzymes.
      One of the major challenges resides in the intricacy of the methodology leading
      to the isolation and characterization of these nucleoside analogues. In this
      video article, we present a detailed protocol for the synthesis of these modified
      analogues using phosphorous(III)-based reagents. In addition, the procedure for
      their biochemical characterization is divulged, with a special emphasis on primer
      extension reactions and TdT tailing polymerization. This detailed protocol will
      be of use for the crafting of modified dNTPs and their further use in chemical
      biology. 

PMID- 24747812
TI  - Efficient Bayesian-based multiview deconvolution.
AB  - Light-sheet fluorescence microscopy is able to image large specimens with high
      resolution by capturing the samples from multiple angles. Multiview deconvolution
      can substantially improve the resolution and contrast of the images, but its
      application has been limited owing to the large size of the data sets. Here we
      present a Bayesian-based derivation of multiview deconvolution that drastically
      improves the convergence time, and we provide a fast implementation using
      graphics hardware. 

PMID- 24747813
TI  - Controlling protein adsorption on graphene for cryo-EM using low-energy hydrogen
      plasmas.
AB  - Despite its many favorable properties as a sample support for biological electron
      microscopy, graphene is not widely used because its hydrophobicity precludes
      reliable protein deposition. We describe a method to modify graphene with a low
      energy hydrogen plasma, which reduces hydrophobicity without degrading the
      graphene lattice. Use of plasma-treated graphene enables better control of
      protein distribution in ice for electron cryo-microscopy and improves image
      quality by reducing radiation-induced sample motion. 

PMID- 24747814
TI  - Validation of noise models for single-cell transcriptomics.
AB  - Single-cell transcriptomics has recently emerged as a powerful technology to
      explore gene expression heterogeneity among single cells. Here we identify two
      major sources of technical variability: sampling noise and global cell-to-cell
      variation in sequencing efficiency. We propose noise models to correct for this,
      which we validate using single-molecule FISH. We demonstrate that gene expression
      variability in mouse embryonic stem cells depends on the culture condition. 

PMID- 24747815
TI  - An infrared reporter to detect spatiotemporal dynamics of protein-protein
      interactions.
AB  - We report a protein-fragment complementation assay (PCA) based on the engineered
      Deinococcus radiodurans infrared fluorescent protein IFP1.4. Unlike previous
      fluorescent protein PCAs, the IFP PCA is reversible, allowing analysis of
      spatiotemporal dynamics of hormone-induced signaling complexes in living yeast
      and mammalian cells at nanometer resolution. The inherently low background of
      infrared fluorescence permitted detection of subcellular reorganization of a
      signaling complex expressed at low abundance. 

PMID- 24747816
TI  - The role of 1.5 tesla MRI and anesthetic regimen concerning cardiac analysis in
      mice with cardiomyopathy.
AB  - Accurate assessment of left ventricular function in rodent models is essential
      for the evaluation of new therapeutic approaches for cardiac diseases. In our
      study, we provide new insights regarding the role of a 1.5 Tesla (T) magnetic
      resonance imaging (MRI) device and different anesthetic regimens on data
      validity. As dedicated small animal MRI and echocardiographic devices are not
      broadly available, we evaluated whether monitoring cardiac function in small
      rodents with a clinical 1.5 T MRI device is feasible. On a clinical
      electrocardiogram (ECG) synchronized 1.5 T MRI scanner we therefore studied
      cardiac function parameters of mice with chronic virus-induced cardiomyopathy.
      Thus, reduced left ventricular ejection fraction (LVEF) could be verified
      compared to healthy controls. However, our results showed a high variability.
      First, anesthesia with medetomidine, midazolam and fentanyl (MMF) led to
      depressed cardiac function parameters and more variability than isoflurane gas
      inhalation anesthesia, especially at high concentrations. Furthermore,
      calculation of an average ejection fraction value from sequenced scans
      significantly reduced the variance of the results. To sum up, we introduce the
      clinical 1.5 T MRI device as a new tool for effective analysis of left
      ventricular function in mice with cardiomyopathy. Besides, we suggest isoflurane
      gas inhalation anesthesia at high concentrations for variance reduction and
      recommend calculation of an average ejection fraction value from multiple
      sequenced MRI scans to provide valid data and a solid basis for further clinical
      testing. 

PMID- 24747818
TI  - Quantitative optical microscopy: measurement of cellular biophysical features
      with a standard optical microscope.
AB  - We describe the use of a standard optical microscope to perform quantitative
      measurements of mass, volume, and density on cellular specimens through a
      combination of bright field and differential interference contrast imagery. Two
      primary approaches are presented: noninterferometric quantitative phase
      microscopy (NIQPM), to perform measurements of total cell mass and subcellular
      density distribution, and Hilbert transform differential interference contrast
      microscopy (HTDIC) to determine volume. NIQPM is based on a simplified model of
      wave propagation, termed the paraxial approximation, with three underlying
      assumptions: low numerical aperture (NA) illumination, weak scattering, and weak
      absorption of light by the specimen. Fortunately, unstained cellular specimens
      satisfy these assumptions and low NA illumination is easily achieved on
      commercial microscopes. HTDIC is used to obtain volumetric information from
      through-focus DIC imagery under high NA illumination conditions. High NA
      illumination enables enhanced sectioning of the specimen along the optical axis.
      Hilbert transform processing on the DIC image stacks greatly enhances edge
      detection algorithms for localization of the specimen borders in three dimensions
      by separating the gray values of the specimen intensity from those of the
      background. The primary advantages of NIQPM and HTDIC lay in their technological
      accessibility using "off-the-shelf" microscopes. There are two basic limitations
      of these methods: slow z-stack acquisition time on commercial scopes currently
      abrogates the investigation of phenomena faster than 1 frame/minute, and
      secondly, diffraction effects restrict the utility of NIQPM and HTDIC to objects
      from 0.2 up to 10 (NIQPM) and 20 (HTDIC) MUm in diameter, respectively. Hence,
      the specimen and its associated time dynamics of interest must meet certain size
      and temporal constraints to enable the use of these methods. Excitingly, most
      fixed cellular specimens are readily investigated with these methods. 

PMID- 24747819
TI  - Process diagnosis using methanogenic Archaea in maize-fed, trace element depleted
      fermenters.
AB  - A mesophilic maize-fed pilot-scale fermenter was severely acidified due to trace
      element (TE) deficiency. Mainly cobalt (0.07 mg * kg(-1) fresh mass (FM)),
      selenium (0.007 mg * kg(-1) FM) and sodium (13 mg * kg(-1) FM) were depleted.
      From this inoculum, three lab-scale flow-through fermenters were operated to
      analyse micronutrient deficiencies and population dynamics in more detail. One
      fermenter was supplemented with selenium, one with cobalt, and one served as
      control. After starvation and recovery of the fermenters, the organic loading
      rate (OLR) was increased. In parallel, the concentration (Real-Time PCR) of
      methanogens and their population composition (amplicon sequencing) was determined
      at the DNA and mRNA level. The parameters Metabolic Quotient (MQ) and cDNA/DNA
      were calculated to assess the activity of the methanogens. The control without TE
      supplementation acidified first at an OLR of 4.0 kg volatile solids (VS) * m(-3)
      * d(-1) while the singular addition of selenium and of cobalt positively
      influenced the fermenter stability up to an OLR of 4.5 or 5.0 kg VS * m(-3) * d(
      1), respectively. In the stable process, the methanogenic populations were
      dominated by probably residual hydrogenotrophic Methanoculleus sp. (DNA-level),
      but representatives of versatile Methanosarcina sp. were most active (cDNA
      level). When the TE supplemented fermenters began to acidify, Methanosarcina spp.
      were dominant in the whole (DNA-level) and the active (cDNA-level) community. The
      acidified control fermenter was dominated by Methanobacteriaceae genus IV. Until
      acidification, the concentration of methanogens increased with higher OLRs. The
      MQ indicated stress metabolism approximately one month before the TVA/TIC ratio
      reached a critical level of 0.7, demonstrating its suitability as early warning
      parameter of process acidification. The development of the cDNA/DNA ratio also
      reflected the increasing methanogenic activity with higher OLRs. Highest cDNA/DNA
      values (ca. 2) were obtained at metabolic strain of the methanogens, at the onset
      of acidification. 

PMID- 24747820
TI  - The role of environmental biotechnology in exploring, exploiting, monitoring,
      preserving, protecting and decontaminating the marine environment.
AB  - In light of the Marine Strategy Framework Directive (MSFD) and the EU Thematic
      Strategy on the Sustainable Use of Natural Resources, environmental biotechnology
      could make significant contributions in the exploitation of marine resources and
      addressing key marine environmental problems. In this paper 14 propositions are
      presented focusing on (i) the contamination of the marine environment, and more
      particularly how to optimize the use of biotechnology-related tools and
      strategies for predicting and monitoring contamination and developing mitigation
      measures; (ii) the exploitation of the marine biological and genetic resources to
      progress with the sustainable, eco-compatible use of the maritime space (issues
      are very diversified and include, for example, waste treatment and recycling,
      anti-biofouling agents; bio-plastics); (iii) environmental/marine biotechnology
      as a driver for a sustainable economic growth. 

PMID- 24747824
TI  - ANRIL inhibits p15(INK4b) through the TGFbeta1 signaling pathway in human
      esophageal squamous cell carcinoma.
AB  - The INK4b-ARF-INK4a gene cluster encodes three tumor suppressors: p15(INK4b),
      p14(ARF), and p16(INK4a). Antisense non-coding RNA in the INK4 locus (ANRIL) is
      transcribed in the opposite direction from this gene cluster. Recent studies
      suggest that ANRIL represses the expression of p15(INK4b), p14(ARF), and
      p16(INK4a); however, the underlying mechanism is unclear. In this study, the
      expressions of ANRIL in human esophageal squamous cell carcinoma (ESCC) tissues
      and matched adjacent non-tumor tissues were examined by quantitative real-time
      polymerase chain reaction. Compared with matched adjacent non-tumor tissues, the
      expression levels of ANRIL in ESCC tissues were significantly increased.
      Furthermore, inhibition of ANRIL was found to increase the expression of
      p15(INK4b) and transforming growth factor beta1 (TGFbeta1) and depletion of ANRIL
      in ESCC cell lines may inhibit cellular proliferation. Thus, our findings suggest
      a significant role of ANRIL in the occurrence and development of ESCC through
      TGFbeta1 signaling pathways. 

PMID- 24747825
TI  - TR alpha 2 exerts dominant negative effects on hypothalamic Trh transcription in
      vivo.
AB  - Mammalian thyroid hormone receptors (TRs) have multiple isoforms, including the
      bona fide receptors that bind T3 (TRalpha1, TRbeta1 and TRbeta2) and a non
      hormone-binding variant, TRalpha2. Intriguingly, TRalpha2 is strongly expressed
      in the brain, where its mRNA levels exceed those of functional TRs. Ablation of
      TRalpha2 in mice results in over-expression of TRalpha1, and a complex phenotype
      with low levels of free T3 and T4, without elevated TSH levels, suggesting an
      alteration in the negative feedback at the hypothalamic-pituitary level. As the
      hypothesis of a potential TRH response defect has never been tested, we explored
      the functional role of TRalpha2 in negative feedback on transcription of
      hypothalamic thyrotropin, Trh. The in vivo transcriptional effects of TRalpha2 on
      hypothalamic Trh were analysed using an in vivo reporter gene approach. Effects
      on Trh-luc expression were examined to that of two, T3 positively regulated genes
      used as controls. Applying in vivo gene transfer showed that TRalpha2 over
      expression in the mouse hypothalphalamus abrogates T3-dependent repression of Trh
      and T3 activation of positively regulated promoters, blocking their physiological
      regulation. Surprisingly, loss of function studies carried out by introducing a
      shTRalpha2 construct in the hypothalamus also blocked physiological T3 dependent
      regulation. Thus, modulating hypothalamic TRalpha2 expression by either gain or
      loss of function abrogated T3 dependent regulation of Trh transcription,
      producing constant transcriptional levels insensitive to feedback. This loss of
      physiological regulation was reflected at the level of the endogenous Trh gene,
      were gain or loss of function held mRNA levels constant. These results reveal the
      as yet undescribed dominant negative role of TRalpha2 over TRalpha1 effect on
      hypothalamic Trh transcription. 

PMID- 24747826
TI  - Adherence of French GPs to chronic neuropathic pain clinical guidelines: results
      of a cross-sectional, randomized, "e" case-vignette survey.
AB  - BACKGROUND AND AIMS: The French Pain Society published guidelines for neuropathic
      pain management in 2010. Our aim was to evaluate the compliance of GPs with these
      guidelines three years later. METHODS: We used "e" case vignette methodology for
      this non interventional study. A national panel of randomly selected GPs was
      included. We used eight "e" case-vignettes relating to chronic pain, differing in
      terms of the type of pain (neuropathic/non neuropathic), etiology (cancer,
      postoperative pain, low back pain with or without radicular pain, diabetes) and
      symptoms. GPs received two randomly selected consecutive "e" case vignettes
      (with/without neuropathic pain). We analyzed their ability to recognize
      neuropathic pain and to prescribe appropriate first-line treatment. RESULTS: From
      the 1265 GPs in the database, we recruited 443 (35.0%), 334 of whom logged onto
      the web site (26.4%) and 319 (25.2%) of whom completed the survey. Among these
      GPs, 170 (53.3%) were aware of the guidelines, 136 (42.6%) were able to follow
      them, and 110 (34.5%) used the DN4 diagnostic tool. Sensitivity for neuropathic
      pain recognition was 87.8% (CI: 84.2%; 91.4%). However, postoperative neuropathic
      pain was less well diagnosed (77.9%; CI: 69.6%; 86.2%) than diabetic pain (95.2%;
      CI: 90.0%; 100.0%), cancer pain (90.6%; CI: 83.5%; 97.8%) and typical radicular
      pain (90.7%; CI: 84.9%; 96.5%). When neuropathic pain was correctly recognized,
      the likelihood of appropriate first-line treatment prescription was 90.6% (CI:
      87.4%; 93.8%). The treatments proposed were pregabaline (71.8%), gabapentine
      (43.9%), amiptriptylline (23.2%) and duloxetine (18.2%). However, ibuprofen
      (11%), acetaminophen-codeine (29.5%) and clonazepam (10%) were still prescribed.
      CONCLUSIONS: The compliance of GPs with clinical practice guidelines appeared to
      be satisfactory, but differed between etiologies.

PMID- 24747827
TI  - A re-assessment of long distance growth and connectivity of neural stem cells
      after severe spinal cord injury.
AB  - As part of the NIH "Facilities of Research Excellence-Spinal Cord Injury" project
      to support independent replication, we repeated key parts of a study reporting
      robust engraftment of neural stem cells (NSCs) treated with growth factors after
      complete spinal cord transection in rats. Rats (n=20) received complete
      transections at thoracic level 3 (T3) and 2weeks later received NSC transplants
      in a fibrin matrix with a growth factor cocktail using 2 different
      transplantation methods (with and without removal of scar tissue). Control rats
      (n=9) received transections only. Hindlimb locomotor function was assessed with
      the BBB scale. Nine weeks post injury, reticulospinal tract axons were traced in
      6 rats by injecting BDA into the reticular formation. Transplants grew to fill
      the lesion cavity in most rats although grafts made with scar tissue removal had
      large central cavities. Grafts blended extensively with host tissue obliterating
      the astroglial boundary at the cut ends, but in most cases there was a well
      defined partition within the graft that separated rostral and caudal parts of the
      graft. In some cases, the partition contained non-neuronal scar tissue. There was
      extensive outgrowth of GFP labeled axons from the graft, but there was minimal
      ingrowth of host axons into the graft revealed by tract tracing and
      immunocytochemistry for 5HT. There were no statistically significant differences
      between transplant and control groups in the degree of locomotor recovery. Our
      results confirm the previous report that NSC transplants can fill lesion cavities
      and robustly extend axons, but reveal that most grafts do not create a continuous
      bridge of neural tissue between rostral and caudal segments. 

PMID- 24747828
TI  - Short-term treatment of adult male zebrafish (Danio Rerio) with 17alpha-ethinyl
      estradiol affects the transcription of genes involved in development and male sex
      differentiation.
AB  - The synthetic estrogen 17alpha-ethinyl estradiol (EE2) disturbs reproduction and
      causes gonadal malformation in fish. Effects on the transcription of genes
      involved in gonad development and function that could serve as sensitive
      biomarkers of reproductive effects in the field is, however, not well known. We
      have studied mRNA expression in testes and liver of adult zebrafish (Danio rerio)
      males treated with 0, 5 or 25 ng/L EE2for 14 days. qPCR analysis showed that the
      mRNA expression of four genes linked to zebrafish male sex determination and
      differentiation, Anti-Mullerian Hormone, Double sex and mab-related protein, Sry
      related HMG box-9a and Nuclear receptor subfamily 5 group number 1b were
      significantly decreased by 25 ng/L, but not 5 ng/L EE2 compared with the levels
      in untreated fish. The decreased transcription was correlated with a previously
      shown spawning failure in these males (Reyhanian et al., 2011. Aquat Toxicol 105,
      41-48), suggesting that decreased mRNA expression of genes regulating male sexual
      function could be involved in the functional sterility. The mRNA level of
      Cytochrome P-45019a, involved in female reproductive development, was unaffected
      by hormone treatment. The transcription of the female-specific Vitellogenin was
      significantly induced in testes. While testicular Androgen Receptor and the
      Estrogen Receptor-alpha mRNA levels were unchanged, Estrogen receptor-beta was
      significantly decreased by 25 ng/L EE2. Hepatic Estrogen Receptor-alpha mRNA was
      significantly increased by both exposure concentrations, while Estrogen Receptor
      beta transcription was unaltered. The decreased transcription of male-predominant
      genes supports a demasculinization of testes by EE2 and might reflect
      reproductive disturbances in the environment.

PMID- 24747829
TI  - DNA damage and oxidative stress induced by acetylsalicylic acid in Daphnia magna.
AB  - Acetylsalicylic acid is a nonsteroidal anti-inflammatory widely used due to its
      low cost and high effectiveness. This compound has been found in water bodies
      worldwide and is toxic to aquatic organisms; nevertheless its capacity to induce
      oxidative stress in bioindicators like Daphnia magna remains unknown. This study
      aimed to evaluate toxicity in D. magna induced by acetylsalicylic acid in water,
      using oxidative stress and DNA damage biomarkers. An acute toxicity test was
      conducted in order to determine the median lethal concentration (48-h LC50) and
      the concentrations to be used in the subsequent subacute toxicity test in which
      the following biomarkers were evaluated: lipid peroxidation, oxidized protein
      content, activity of the antioxidant enzymes superoxide dismutase, catalase, and
      glutathione peroxidase, and level of DNA damage. Lipid peroxidation level and
      oxidized protein content were significantly increased (p<0.05), and antioxidant
      enzymes significantly altered with respect to controls; while the DNA damage were
      significantly increased (p<0.05) too. In conclusion, acetylsalicylic acid induces
      oxidative stress and DNA damage in D. magna. 

PMID- 24747830
TI  - Oculomotor capture by supraliminal and subliminal onset singletons: the role of
      contrast polarity.
AB  - According to a top-down explanation of subliminal oculomotor capture, only
      subliminal distractors with a contrast polarity matching that of the searched-for
      targets should capture attention. For instance, when looking for white targets
      only subliminal white but not black distractors should capture attention. In
      contrast, according to a bottom-up explanation of such capture effects,
      subliminal distractors with a contrast polarity different to that of the searched
      for targets should also capture attention. For instance, even when looking for
      white targets, subliminal black distractors should capture attention. Here, we
      used subliminal singleton-onset distractors in the same vertical hemifield as the
      target versus singleton-onset distractors in the opposite vertical field to the
      target, and tested whether oculomotor capture by these distractors depended on a
      match between the searched-for target contrasts and the distractor contrasts, by
      measuring saccade latency, saccade trajectory deviation, and saccade endpoint
      deviation. We found evidence for oculomotor capture: subliminal distractors in
      the opposite field delayed saccade execution towards the target. This delay was
      found in comparison to subliminal distractors in the same hemifield as the
      target. In line with a bottom-up explanation, this delay was independent of the
      similarity between the distractor contrast polarity and the searched-for target
      contrast polarity. Together with the subliminality of the distractors, the
      experiment confirmed bottom-up oculomotor capture by subliminal singleton-onsets.

PMID- 24747832
TI  - Ionic channels underlying the ventricular action potential in zebrafish embryo.
AB  - Over the last years zebrafish has become a popular model in the study of cardiac
      physiology, pathology and pharmacology. Recently, the application of the 3Rs
      regulation and the characteristics of the embryo have reduced the use of adult
      zebrafish use in many studies. However, the zebrafish embryo cardiac physiology
      is poorly characterized since most works have used indirect techniques and direct
      recordings of cardiac action potential and ionic currents are scarce. In order to
      optimize the zebrafish embryo model, we used electrophysiological,
      pharmacological and immunofluorescence tools to identify the characteristics and
      the ionic channels involved in the ventricular action potentials of zebrafish
      embryos. The application of Na(+) or T-type Ca(+2) channel blockers eliminated
      the cardiac electrical activity, indicating that the action potential upstroke
      depends on Na(+) and T-type Ca(+2) currents. The plateau phase depends on L-type
      Ca(+2) channels since it is abolished by specific blockade. The direct channel
      blockade indicates that the action potential repolarization and diastolic
      potential depends on ERG K(+) channels. The presence in the embryonic heart of
      the Nav1.5, Cav1.2, Cav3.2 and ERG channels was also confirmed by
      immunofluorescence, while the absence of effect of specific blockers and
      immunostaining indicate that two K(+) repolarizing currents present in human
      heart, Ito and IKs, are absent in the embryonic zebrafish heart. Our results
      describe the ionic channels present and its role in the zebrafish embryo heart
      and support the use of zebrafish embryos to study human diseases and their use
      for drug testing. 

PMID- 24747833
TI  - Effects of electroconvulsive therapy on serum levels of brain-derived
      neurotrophic factor and nerve growth factor in treatment resistant major
      depression.
AB  - OBJECTIVES: This study aimed to investigate the effects of electroconvulsive
      treatment on serum BDNF and NGF levels in patients with treatment-resistant major
      depression. METHODS: Thirty patients with treatment-resistant major depression
      and 30 healthy controls were included in the study. The patients' serum BDNF and
      NGF levels were measured three times; before treatment (T0), when the clinical
      response occurred (T1) and at the end of treatment (T2). RESULTS: The reduction
      detected in the HAM-D scores with ECT during the T0-T1, T1-T2 and T0-T2 periods
      was found to be statistically significant. In the patient group, increase in the
      mean BDNF levels after ECT treatment was found to be statistically significant
      (p<0.05). Significant increases in serum BDNF levels with ECT were lower than in
      the control group, and the serum NGF levels did not increase significantly. There
      was no relationship between the severity of the depression and serum BDNF and NGF
      levels (p>0.05). CONCLUSIONS: This study evaluated the role of neurotrophic
      factors in the etiopathogenesis of major depression. Future studies should
      investigate the relationship between neurotrophic factors with neuroendocrine and
      genetic processes to elucidate the psychobiology and treatment of mental
      disorders.

PMID- 24747831
TI  - Calreticulin contributes to C1q-dependent recruitment of microglia in the leech
      Hirudo medicinalis following a CNS injury.
AB  - BACKGROUND: The medicinal leech is considered as a complementary and appropriate
      model to study immune functions in the central nervous system (CNS). In a context
      in which an injured leech's CNS can naturally restore normal synaptic
      connections, the accumulation of microglia (immune cells of the CNS that are
      exclusively resident in leeches) has been shown to be essential at the lesion to
      engage the axonal sprouting. HmC1q (Hm for Hirudo medicinalis) possesses
      chemotactic properties that are important in the microglial cell recruitment by
      recognizing at least a C1q binding protein (HmC1qBP alias gC1qR). MATERIAL AND
      METHODS: Recombinant forms of C1q were used in affinity purification and in vitro
      chemotaxis assays. Anti-calreticulin antibodies were used to neutralize C1q
      mediated chemotaxis and locate the production of calreticulin in leech CNS.
      RESULTS: A newly characterized leech calreticulin (HmCalR) has been shown to
      interact with C1q and participate to the HmC1q-dependent microglia accumulation.
      HmCalR, which has been detected in only some microglial cells, is consequently a
      second binding protein for HmC1q, allowing the chemoattraction of resident
      microglia in the nerve repair process. CONCLUSIONS: These data give new insight
      into calreticulin/C1q interaction in an immune function of neuroprotection,
      suggesting another molecular target to use in investigation of microglia
      reactivity in a model of CNS injury.

PMID- 24747834
TI  - Brain glucose metabolism in adults with ataxia-telangiectasia and their
      asymptomatic relatives.
AB  - Ataxia-telangiectasia is a recessive genetic disorder (ATM is the mutated gene)
      of childhood with severe motor impairments and whereas homozygotes manifest the
      disorder, heterozygotes are asymptomatic. Structural brain imaging and post
      mortem studies in individuals with ataxia-telangiectasia have reported cerebellar
      atrophy; but abnormalities of motor control characteristic of extrapyramidal
      dysfunction suggest impairment of broader motor networks. Here, we investigated
      possible dysfunction in other brain areas in individuals with ataxia
      telangiectasia and tested for brain changes in asymptomatic relatives to assess
      if heterozygocity affects brain function. We used positron emission tomography
      and (18)F-fluorodeoxyglucose to measure brain glucose metabolism (quantified as
      umol/100 g/min), which serves as a marker of brain function, in 10 adults with
      ataxia-telangiectasia, 19 non-affected adult relatives (12 siblings, seven
      parents) and 29 age-matched healthy controls. Statistical parametric mapping and
      region of interest analyses were used to compare individuals with ataxia
      telangiectasia, asymptomatic relatives, and unrelated controls. We found that
      participants with ataxia-telangiectasia had lower metabolism in cerebellar
      hemispheres (14%, P < 0.001), anterior vermis (40%, P < 0.001) and fusiform gyrus
      (20%, P < 0.001) compared with controls or siblings, and lower metabolism in
      hippocampus (12%, P = 0.05) compared with controls, and showed significant
      intersubject variability (decreases in vermis ranged from 18% to 60%).
      Participants with ataxia-telangiectasia also had higher metabolism in globus
      pallidus (16%, P = 0.05), which correlated negatively with motor performance.
      Asymptomatic relatives had lower metabolism in anterior vermis (12%; P = 0.01)
      and hippocampus (19%; P = 0.002) than controls. Our results indicate that, in
      addition to the expected decrease in cerebellar metabolism, participants with
      ataxia-telangiectasia had widespread changes in metabolic rates including
      hyperactivity in globus pallidus indicative of basal ganglia involvement. Changes
      in basal ganglia metabolism offer potential insight into targeting strategies for
      therapeutic deep brain stimulation. Our finding of decreased metabolism in vermis
      and hippocampus of asymptomatic relatives suggests that heterozygocity influences
      the function of these brain regions. 

PMID- 24747835
TI  - Reduced dendritic arborization and hyperexcitability of pyramidal neurons in a
      Scn1b-based model of Dravet syndrome.
AB  - Epileptic encephalopathies, including Dravet syndrome, are severe treatment
      resistant epilepsies with developmental regression. We examined a mouse model
      based on a human beta1 sodium channel subunit (Scn1b) mutation. Homozygous mutant
      mice shared phenotypic features and pharmaco-sensitivity with Dravet syndrome.
      Patch-clamp analysis showed that mutant subicular and layer 2/3 pyramidal neurons
      had increased action potential firing rates, presumably as a consequence of their
      increased input resistance. These changes were not seen in L5 or CA1 pyramidal
      neurons. This raised the concept of a regional seizure mechanism that was
      supported by data showing increased spontaneous synaptic activity in the
      subiculum but not CA1. Importantly, no changes in firing or synaptic properties
      of gamma-aminobutyric acidergic interneurons from mutant mice were observed,
      which is in contrast with Scn1a-based models of Dravet syndrome. Morphological
      analysis of subicular pyramidal neurons revealed reduced dendritic arborization.
      The antiepileptic drug retigabine, a K+ channel opener that reduces input
      resistance, dampened action potential firing and protected mutant mice from
      thermal seizures. These results suggest a novel mechanism of disease genesis in
      genetic epilepsy and demonstrate an effective mechanism-based treatment of the
      disease.

PMID- 24747836
TI  - The utilization of oropharyngeal intratracheal PAMP administration and
      bronchoalveolar lavage to evaluate the host immune response in mice.
AB  - The host immune response to pathogens is a complex biological process. The
      majority of in vivo studies classically employed to characterize host-pathogen
      interactions take advantage of intraperitoneal injections of select bacteria or
      pathogen associated molecular patterns (PAMPs) in mice. While these techniques
      have yielded tremendous data associated with infectious disease pathobiology,
      intraperitoneal injection models are not always appropriate for host-pathogen
      interaction studies in the lung. Utilizing an acute lung inflammation model in
      mice, it is possible to conduct a high resolution analysis of the host innate
      immune response utilizing lipopolysaccharide (LPS). Here, we describe the methods
      to administer LPS using nonsurgical oropharyngeal intratracheal administration,
      monitor clinical parameters associated with disease pathogenesis, and utilize
      bronchoalveolar lavage fluid to evaluate the host immune response. The techniques
      that are described are widely applicable for studying the host innate immune
      response to a diverse range of PAMPs and pathogens. Likewise, with minor
      modifications, these techniques can also be applied in studies evaluating
      allergic airway inflammation and in pharmacological applications. 

PMID- 24747837
TI  - Selective molecular recognition by nanoscale environments in a supported iridium
      cluster catalyst.
AB  - The active sites of enzymes are contained within nanoscale environments that
      exhibit exquisite levels of specificity to particular molecules. The development
      of such nanoscale environments on synthetic surfaces, which would be capable of
      discriminating between molecules that would nominally bind in a similar way to
      the surface, could be of use in nanosensing, selective catalysis and gas
      separation. However, mimicking such subtle behaviour, even crudely, with a
      synthetic system remains a significant challenge. Here, we show that the reactive
      sites on the surface of a tetrairidium cluster can be controlled by using three
      calixarene-phosphine ligands to create a selective nanoscale environment at the
      metal surface. Each ligand is 1.4 nm in length and envelopes the cluster core in
      a manner that discriminates between the reactivities of the basal-plane and
      apical iridium atoms. CO ligands are initially present on the clusters and can be
      selectively removed from the basal-plane sites by thermal dissociation and from
      the apical sites by reactive decarbonylation with the bulky reactant
      trimethylamine-N-oxide. Both steps lead to the creation of metal sites that can
      bind CO molecules, but only the reactive decarbonylation step creates vacancies
      that are also able to bond to ethylene, and catalyse its hydrogenation.

PMID- 24747838
TI  - Quantitative imaging of single mRNA splice variants in living cells.
AB  - Alternative messenger RNA (mRNA) splicing is a fundamental process of gene
      regulation, and errors in RNA splicing are known to be associated with a variety
      of different diseases. However, there is currently a lack of quantitative
      technologies for monitoring mRNA splice variants in cells. Here, we show that a
      combination of plasmonic dimer probes and hyperspectral imaging can be used to
      detect and quantify mRNA splice variants in living cells. The probes are made
      from gold nanoparticles functionalized with oligonucleotides and can hybridize to
      specific mRNA sequences, forming nanoparticle dimers that exhibit distinct
      spectral shifts due to plasmonic coupling. With this approach, we show that the
      spatial and temporal distribution of three selected splice variants of the breast
      cancer susceptibility gene, BRCA1, can be monitored at single-copy resolution by
      measuring the hybridization dynamics of the nanoplasmonic dimers. Our study
      provides insights into RNA and its transport in living cells, which could improve
      our understanding of cellular protein complexes, pharmacogenomics, genetic
      diagnosis and gene therapies. 

PMID- 24747839
TI  - Electron microscopy: a phase transition glides into view.

PMID- 24747840
TI  - Subnanosecond incubation times for electric-field-induced metallization of a
      correlated electron oxide.
AB  - Strong interactions, or correlations, between the d or f electrons in transition
      metal oxides lead to various types of metal-insulator transitions that can be
      triggered by external parameters such as temperature, pressure, doping, magnetic
      fields and electric fields. Electric-field-induced metallization of such
      materials from their insulating states could enable a new class of ultrafast
      electronic switches and latches. However, significant questions remain about the
      detailed nature of the switching process. Here, we show, in the canonical metal
      to-insulator transition system V2O3, that ultrafast voltage pulses result in its
      metallization only after an incubation time that ranges from ~150 ps to many
      nanoseconds, depending on the electric field strength. We show that these
      incubation times can be accounted for by purely thermal effects and that
      intrinsic electronic-switching mechanisms may only be revealed using larger
      electric fields at even shorter timescales.

PMID- 24747841
TI  - Atomic mechanism of the semiconducting-to-metallic phase transition in single
      layered MoS2.
AB  - Phase transitions can be used to alter the properties of a material without
      adding any additional atoms and are therefore of significant technological value.
      In a solid, phase transitions involve collective atomic displacements, but such
      atomic processes have so far only been investigated using macroscopic approaches.
      Here, we show that in situ scanning transmission electron microscopy can be used
      to follow the structural transformation between semiconducting (2H) and metallic
      (1T) phases in single-layered MoS2, with atomic resolution. The 2H/1T phase
      transition involves gliding atomic planes of sulphur and/or molybdenum and
      requires an intermediate phase (alpha-phase) as a precursor. The migration of two
      kinds of boundaries (beta- and gamma-boundaries) is also found to be responsible
      for the growth of the second phase. Furthermore, we show that areas of the 1T
      phase can be controllably grown in a layer of the 2H phase using an electron
      beam. 

PMID- 24747842
TI  - Shock wave application to cell cultures.
AB  - Shock waves nowadays are well known for their regenerative effects. Basic
      research findings showed that shock waves do cause a biological stimulus to
      target cells or tissue without any subsequent damage. Therefore, in vitro
      experiments are of increasing interest. Various methods of applying shock waves
      onto cell cultures have been described. In general, all existing models focus on
      how to best apply shock waves onto cells. However, this question remains: What
      happens to the waves after passing the cell culture? The difference of the
      acoustic impedance of the cell culture medium and the ambient air is that high,
      that more than 99% of shock waves get reflected! We therefore developed a model
      that mainly consists of a Plexiglas built container that allows the waves to
      propagate in water after passing the cell culture. This avoids cavitation effects
      as well as reflection of the waves that would otherwise disturb upcoming ones.
      With this model we are able to mimic in vivo conditions and thereby gain more and
      more knowledge about how the physical stimulus of shock waves gets translated
      into a biological cell signal ("mechanotransduction"). 

PMID- 24747844
TI  - Pulse train induced rotational excitation and orientation of a polar molecule.
AB  - We investigate theoretically the rotational excitation and field free molecular
      orientation of polar HBr molecule, interacting with train of ultrashort laser
      pulses. By adjusting the number of pulses, pulse period and the intensity of the
      pulse, one can suppress a population while simultaneously enhancing the desired
      population in particular rotational state. We have used train of laser pulses of
      different shaped pulse envelopes. The dynamics and orientation of molecules in
      the presence of pulse train of different shapes is studied and explained. 

PMID- 24747843
TI  - Molecular characterization and expression profiling of the protein disulfide
      isomerase gene family in Brachypodium distachyon L.
AB  - Protein disulfide isomerases (PDI) are involved in catalyzing protein disulfide
      bonding and isomerization in the endoplasmic reticulum and functions as a
      chaperone to inhibit the aggregation of misfolded proteins. Brachypodium
      distachyon is a widely used model plant for temperate grass species such as wheat
      and barley. In this work, we report the first molecular characterization,
      phylogenies, and expression profiles of PDI and PDI-like (PDIL) genes in B.
      distachyon in different tissues under various abiotic stresses. Eleven PDI and
      PDIL genes in the B. distachyon genome by in silico identification were evenly
      distributed across all five chromosomes. The plant PDI family has three conserved
      motifs that are involved in catalyzing protein disulfide bonding and
      isomerization, but a different exon/intron structural organization showed a high
      degree of structural differentiation. Two pairs of genes (BdPDIL4-1 and BdPDIL4
      2; BdPDIL7-1 and BdPDIL7-2) contained segmental duplications, indicating each
      pair originated from one progenitor. Promoter analysis showed that Brachypodium
      PDI family members contained important cis-acting regulatory elements involved in
      seed storage protein synthesis and diverse stress response. All Brachypodium PDI
      genes investigated were ubiquitously expressed in different organs, but
      differentiation in expression levels among different genes and organs was clear.
      BdPDIL1-1 and BdPDIL5-1 were expressed abundantly in developing grains,
      suggesting that they have important roles in synthesis and accumulation of seed
      storage proteins. Diverse treatments (drought, salt, ABA, and H2O2) induced up-
      and down-regulated expression of Brachypodium PDI genes in seedling leaves.
      Interestingly, BdPDIL1-1 displayed significantly up-regulated expression
      following all abiotic stress treatments, indicating that it could be involved in
      multiple stress responses. Our results provide new insights into the structural
      and functional characteristics of the plant PDI gene family. 

PMID- 24747845
TI  - Biosynthesis and characterization of Acalypha indica mediated copper oxide
      nanoparticles and evaluation of its antimicrobial and anticancer activity.
AB  - Copper oxide nanoparticles were synthesized by biological method using aqueous
      extract of Acalypha indica leaf and characterized by UV-visible spectroscopy,
      XRD, FT-IR, SEM TEM and EDX analysis. The synthesised particles were highly
      stable, spherical and particle size was in the range of 26-30 nm. The
      antimicrobial activity of A.indica mediated copper oxide nanoparticles was tested
      against selected pathogens. Copper oxide nanoparticles showed efficient
      antibacterial and antifungal effect against Escherichia coli, Pseudomonas
      fluorescens and Candida albicans. The cytotoxicity activity of A.indica mediated
      copper nanoparticles was evaluated by MTT assay against MCF-7 breast cancer cell
      lines and confirmed that copper oxide nanoparticles have cytotoxicity activity.

PMID- 24747846
TI  - Applicability of a Diffuse Reflectance Infrared Fourier Transform handheld
      spectrometer to perform in situ analyses on Cultural Heritage materials.
AB  - This work studies the applicability of a Diffuse Reflectance Infrared Fourier
      Transform handheld device to perform in situ analyses on Cultural Heritage
      assets. This portable diffuse reflectance spectrometer has been used to
      characterise and diagnose the conservation state of (a) building materials of the
      Guevara Palace (15th century, Segura, Basque Country, Spain) and (b) different
      19th century wallpapers manufactured by the Santa Isabel factory (Vitoria
      Gasteiz, Basque Country, Spain) and by the well known Dufour and Leroy
      manufacturers (Paris, France), all of them belonging to the Torre de los Varona
      Castle (Villanane, Basque Country, Spain). In all cases, in situ measurements
      were carried out and also a few samples were collected and measured in the
      laboratory by diffuse reflectance spectroscopy (DRIFT) in order to validate the
      information obtained by the handheld instrument. In the analyses performed in
      situ, distortions in the diffuse reflectance spectra can be observed due to the
      presence of specular reflection, showing the inverted bands caused by the
      Reststrahlen effect, in particular on those IR bands with the highest absorption
      coefficients. This paper concludes that the results obtained in situ by a diffuse
      reflectance handheld device are comparable to those obtained with laboratory
      diffuse reflectance spectroscopy equipment and proposes a few guidelines to
      acquire good spectra in the field, minimising the influence caused by the
      specular reflection. 

PMID- 24747847
TI  - Controlling of dielectrical properties of hydroxyapatite by ethylenediamine
      tetraacetic acid (EDTA) for bone healing applications.
AB  - The hydroxyapatite (HAp) samples in the presence of various amounts of
      ethylenediamine tetraacetic acid (EDTA) were prepared by sol-gel method. The
      effects of EDTA on the crystallinity, phase structure, chemical, micro-structural
      and dielectric properties of HAp samples were investigated. With the addition of
      EDTA, the average crystallite size of the HAp samples is gradually decreased from
      30 to 22 nm and the crystallinity is in the range of 65-71%. The values of the
      lattice parameters (a and c) and volume of the unit cell are decreased by stages
      with the addition of EDTA. The dielectric parameters such as relative
      permittivity, dielectric loss and relaxation time are affected by the adding of
      EDTA. The alternating current conductivity of the as-synthesized hydroxyapatites
      increases with the increasing frequency and obeys the universal power law
      behavior. The HAp samples exhibit a non-Debye relaxation mechanism. The obtained
      results that the dielectrical parameters of the HAp sample can be controlled by
      EDTA.

PMID- 24747848
TI  - Synthesis, structural and luminescence properties of Mn doped ZnO/Zn2SiO4
      composite microphosphor.
AB  - Manganese doped ZnO/Zn2SiO4 (MZS) composite phosphors were successfully prepared
      by conventional solid state reaction method. The structural and optical
      properties of as-prepared samples were analysed by means of XRD, SEM, PLE and PL.
      The result shows that the samples consist of both ZnO and ZnSiO4 phases which
      confirms the composite phosphor. The strain acting on the phosphor is found to be
      in the range of 0.0040-0.0058 for different concentration of Mn(2+) doping. The
      doping of Mn(2+) significantly influences the optical properties of phosphor.
      Under 266 nm laser excitation samples show green emission (~530 nm) and with 355
      nm laser excitation blue emission (~441 nm) is shown. The enhancement of
      luminescence intensity is achieved with Mn(2+) doping up to an optimum
      concentration (10 at.%) and then decreases. On 266 nm excitation, blue emission
      intensity decreases with Mn(2+) doping. This composite phosphor shows both blue
      and green emission under different excitations.

PMID- 24747849
TI  - Time-dependent density functional theory study on the excited-state
      intramolecular proton transfer in salicylaldehyde.
AB  - Time-dependent density functional theory method was performed to investigate the
      excited state intramolecular hydrogen bond dynamics of salicylaldehyde (SA). The
      geometric structures and IR spectra in the ground state S0 state and the excited
      state S1 state of SA are calculated using the density functional theory (DFT) and
      the time-dependent density functional theory (TDDFT) methods, respectively. In
      addition, the absorption and fluorescence peaks are also calculated using TDDFT
      methods. It is noted that the calculated large Stokes shift is in good agreement
      with the experimental results. Furthermore, our results have demonstrated that
      the excited state intramolecular proton transfer (ESIPT) process happens upon
      photoexcitation, which are distinct monitored by the formation and disappearance
      of the characteristic peaks of IR spectra involved in the formation of hydrogen
      bonds in different states and in the potential energy curves. We find that the
      hydrogen bonded quasi-aromatic chelating ring in the excited state becomes
      smaller which can facilitate the ESIPT process. The results presented here
      suggest that the ESIPT process of the SA molecule in the excited state can be
      attributed to the electronegativity change of O1 induced by excitation. 

PMID- 24747850
TI  - Synthesis, spectral (IR, UV-Vis and variable temperature NMR) characterization
      and crystal structure of (N-benzyl-N-furfuryldithicarbamato-S,S')(thiocyanato
      N)(triphenylphosphine)nickel(II).
AB  - Planar (N-benzyl-N-furfuryldithiocarbamato-S,S')(thiocyanato
      N)(triphenylphospine)nickel(II), [Ni(bfdtc)(NCS)(PPh3)], (1) was prepared from
      bis(N-benzyl-N-furfuryldithiocarbamato-S,S')nickel(II), [Ni(bfdtc)2], (2) and
      characterized by elemental analysis, cyclic voltammetry, electronic, IR and
      variable temperature (1)H and (13)C NMR spectra. For complex 1, the thioureide
      vCN value is shifted to higher wavenumber compared to 2 and N(13)CS2 carbon
      signal observed for 1 is additionally shielded compared to the parent complex 2,
      suggesting increased strength of the thioureide bond due to the presence of the
      pi-accepting phosphine. In the room temperature (13)C NMR spectrum of 1, two
      pseudo doublets are observed in the aliphatic region. Variable temperature (13)C
      NMR spectral studies suggest that the fast thiocyanate exchange appears to be
      responsible for the appearance of pseudo doublets. Single crystal X-ray
      structural analysis of 1 and 2 confirm the presence of four coordinated nickel in
      a distorted square planar arrangement with the NiS2PN and NiS4 chromophores,
      respectively. The NiS bonds are symmetric in 2 (2.1914(14) and 2.2073(13)A). But
      significant asymmetry in NiS bond distances was observed in 1 (2.2202(8)A and
      2.1841A). This observation clearly supports the less effective trans effect of
      SCN(-) over PPh3. Cyclic voltammetric studies revealed easier reduction of
      nickel(II) to nickel(I) in complex 1 compared to 2. 

PMID- 24747851
TI  - Complexes of cis-dioxomolybdenum(VI) and oxovanadium(IV) with a tridentate ONS
      donor ligand: synthesis, spectroscopic properties, X-ray crystal structure and
      catalytic activity.
AB  - New cis-dioxomolybdenum(VI) and oxovanadium(IV) complexes of the Schiff base,
      derived from S-methyl dithiocarbazate and 2,3-dihydroxybenzaldehyde (H2dhsm),
      have been synthesized. The complexes of the type cis-[MoO2(dhsm)] (1a), cis
      [MoO2(dhsm)(D)] (1b-1d) [D=neutral monodentate ligand; EtOH, pyridine (py) or
      imidazole (imz)], [VO(dhsm)(NN)] (2a, 2b) [NN=2,2'-bipyridine (bipy) or 1,10
      phenanthroline (phen)] and [VO(dhsm)] (2c) have been isolated, characterized by
      (1)H NMR, IR, UV-Vis and EPR spectral studies and investigated by cyclic
      voltammetry. The X-ray crystal structure of cis-[MoO2(dhsm)(EtOH)] (1b) has been
      determined and shows that the complex has a distorted octahedral geometry in
      which the H2dhsm behaves as a dianionic ONS tridentate ligand coordinating via
      phenoxide oxygen, hydrazinic nitrogen and thiolate sulfur. The oxomolybdenum(IV)
      complex [MoO(dhsm)] (1e) has obtained from dioxomolybdenum(VI) complex (1b) by
      oxo abstraction with PPh3. The reactivity of the complexes toward catalytic
      oxidation of alcohols in the presence of H2O2 and t-BuOOH as co-oxidants under
      solvent free conditions is reported. 

PMID- 24747852
TI  - Spectral characterization of some second harmonic generation materials from the
      amino acid family: L-Threonine and L-prolinium tartrate.
AB  - Single crystals of the organic non-linear optical materials L-threonine (I) and L
      prolinium tartrate (II) were grown using a home-made crystal growth setup (MKN
      setup). The grown crystals were characterized using X-ray diffraction, Infrared
      (IR), UV-vis-NIR and Circular dichroism (CD) spectroscopy. Measurements of
      Vicker's microhardness, laser damage threshold (LDT) values and second harmonic
      generation (SHG) efficiencies are reported. Thermal and dielectric studies were
      also carried out.

PMID- 24747853
TI  - Spectroscopic and structural study of some 2,5-hexanedione
      bis(salicyloylhydrazone) complexes: crystal structures of its Ni(II) and Cu(II)
      complexes and N-(2,5-dimethyl-1H-pyrrol-1-yl)-2-hydroxy-benzamide.
AB  - The reaction between 2,5-hexanedione and salicylic acid hydrazide produced two
      compounds: 2,5-hexanedione bis(salicyloylhydrazone) [HDSH] (ethanol insoluble)
      and N-(2,5-dimethyl-1H-pyrrol-1-yl)-2-hydroxybenzamide [DPH] (ethanol soluble).
      HDSH formed complexes with Co(II), Ni(II), Cu(II), Zn(II), Cd(II), Hg(II) and
      Pd(II) which are characterized by elemental analyses, spectra (IR, (1)H NMR, ESR
      and MS), thermal and magnetic measurements. The crystals of [Ni(HDSH
      2H)(EtOH)(H2O)] and [Cu(HDSH-2H)] were solved having octahedral and square-planar
      geometries, respectively. The other complexes have the formulae [Co(HDSH
      2H)(H2O)2], [Cu(HDSH-H)2], [Zn(HDSH-2H)(H2O)2], [Cd2(HDSH-4H)(H2O)4], [Cd2(HDSH
      2H)(H2O)4Cl2]; [Hg(HDSH-2H)] and [Pd2(HDSH-4H)(H2O)4]. The obtained complexes are
      stable in air and non-hygroscopic. The magnetic moments and electronic spectra of
      the complexes provide different geometries. The ESR spectra support the
      mononuclear geometry for [Cu(HDSH-2H)] and [Cu(HDSH-H)2]. The thermal
      decomposition of the complexes revealed the coordinated waters as well as the end
      product which is in most cases the metal oxide. The crystal structure of N-(2,5
      dimethyl-1H-pyrrol-1-yl)-2-hydroxybenzamide is solved by X-ray technique. 

PMID- 24747854
TI  - Interaction between pirenoxine and bovine serum albumin in aqueous solution.
AB  - This work concerns the interaction of prenoxine sodium (PRX) and bovine serum
      albumin (BSA), which was conducted by spectroscopic means: fluorescence spectra,
      ultraviolet-visible spectra (UV-vis) and circular dichroism spectra (CD spectra)
      in physiological conditions. The results revealed the PRX can quench the
      fluorescence of BSA remarkably in aqueous solution. The quench mechanism has been
      obtained after corrected the fluorescence intensities for inner filter effects.
      The binding constants (Ka) were calculated according to the relevant fluorescence
      data at different temperatures. Moreover, from a series of analyses, we have
      obtained the binding sites, the binding distance and binding force. The effect of
      PRX on the conformation of BSA has been analyzed using synchronous fluorescence
      under experimental conditions. In addition, the CD spectra proved that the
      secondary structure of BSA changed in the presence of PRX in aqueous solution. 

PMID- 24747855
TI  - Fluorescence properties of 3-amino phenylboronic acid and its interaction with
      glucose and ZnS:Cu quantum dots.
AB  - Preliminary results of a study of the interaction between 3-amino phenylboronic
      acid and glucose or ZnS:Cu quantum dots are presented in this paper. ZnS:Cu
      quantum dots with mercaptopropionic acid as a capping agent were obtained and
      characterized. Quenching of 3-amino phenylboronic acid fluorescence was studied
      by steady-state and timeresolved measurements. For fluorescence quenching with
      glucose the results of steady-state measurements fulfill Stern-Volmer equation.
      The quenching constants are increasing with growing pH. The decay of fluorescence
      is monoexponential with lifetime about 8.4 ns, which does not depend on pH and
      glucose concentration indicating static quenching. The quenching constant can be
      interpreted as apparent equilibrium constant of estrification of boronic group
      with diol. Quantum dots are also quenching 3-amino phenylboronic acid
      fluorescence. Fluorescence lifetime, in this case, is slightly decreasing with
      increasing concentration of quantum dots. The quenching constants are increasing
      slightly with pH's growth. Quenching mechanism of 3-amino phenylboronic acid
      fluorescence by quantum dots needs further experiments to be fully explained.

PMID- 24747856
TI  - Protonation effects on the UV/Vis absorption spectra of imatinib: a theoretical
      and experimental study.
AB  - An experimental and theoretical investigation of protonation effects on the
      UV/Vis absorption spectra of imatinib showed systematic changes of absorption
      depending on the pH, and a new absorption band appeared below pH 2. These changes
      in the UV/Vis absorption spectra were interpreted using quantum chemical
      calculations. The geometry of various imatinib cations in the gas phase and in
      ethanol solution was optimized with the DFT/B3LYP method. The resultant
      geometries were compared to the experimentally determined crystal structures of
      imatinib salts. The semi-empirical ZINDO-CI method was employed to calculate the
      absorption lines and electronic transitions. Our study suggests that the
      formation of the extra near-UV absorption band resulted from an increase of
      imatinib trication concentration in the solution, while the rapid increase of the
      first absorption maximum could be attributed to both the formation of imatinib
      trication and tetracation. 

PMID- 24747857
TI  - Synthesis, spectroscopic, anticancer and antibacterial studies of Ni(II) and
      Cu(II) complexes with 2-carboxybenzaldehyde thiosemicarbazone.
AB  - Ni(II) and Cu(II) complexes of 2-carboxybenzaldehyde thiosemicarbazone (L) were
      synthesized and investigated by their spectral and analytical data. These newly
      synthesized complexes have a composition of M(L)X(H2O)2 (where M=Ni(II), Cu(II)
      and X=Cl(-), NO3(-), CH3COO(-)) and (L) is the tridentate Schiff base ligand. The
      ligand and its complexes have been characterized on the basis of analytical,
      molar conductivity, magnetic susceptibility measurements, FT-IR, ESR, (1)H NMR
      and electronic spectral analysis. All the compounds were non-electrolytic in
      nature. On the basis of spectral studies an octahedral geometry has been assigned
      for Ni(II) and a tetragonal geometry for Cu(II) complexes. The ligand and its
      metal complexes were screened for their anticancer studies against human breast
      cancer cell lines MCF-7 and calculated minimum inhibitory concentration and also
      for antibacterial activity using Kirby-Bauer single disk susceptibility test. 

PMID- 24747858
TI  - Polarized fluorescence microscopy analysis of patterned, polymerized
      perfluorotetradecanoic acid-pentacosadiynoic acid thin films.
AB  - Photoillumination of mixed films comprised of the photopolymerizable fatty acid
      10,12 pentacosadiynoic acid and perfluorotetradecanoic acid deposited onto glass
      substrates gives rise to the formation of oriented polydiacetylene photopolymer
      fibers. The degree of polymer fiber orientation was investigated using dual-view,
      polarized fluorescence microscopy of the polydiacetylene, which allowed for
      characterization of individual fluorescent polymer fibers after
      photopolymerization, as well as comparison of the orientation of different fibers
      within the same sample. Measurements indicated that individual fibers consisted
      of multiple photopolymer strands with various orientations, and that there was a
      preferred orientation for fibers in the film as a whole. The fibers were
      preferentially oriented at an angle of approximately 60 degrees  to the direction
      of film compression during deposition from a Langmuir trough, with orientation
      being the result of mechanical stress exerted by the compression barriers coupled
      with rotation of the polymer fibers during film draining. These measurements were
      complemented with conventional "bulk" fluorescence polarization experiments, and
      compared with mixed film structures described previously for these systems at the
      air-water interface using Brewster angle microscopy. 

PMID- 24747859
TI  - Quantum-mechanical DFT calculation supported Raman spectroscopic study of some
      amino acids in bovine insulin.
AB  - In this article Quantum mechanical (QM) calculations by Density Functional Theory
      (DFT) have been performed of all amino acids present in bovine insulin. Simulated
      Raman spectra of those amino acids are compared with their experimental spectra
      and the major bands are assigned. The results are in good agreement with
      experiment. We have also verified the DFT results with Quantum mechanical
      molecular mechanics (QM/MM) results for some amino acids. QM/MM results are very
      similar with the DFT results. Although the theoretical calculation of individual
      amino acids are feasible, but the calculated Raman spectrum of whole protein
      molecule is difficult or even quite impossible task, since it relies on lengthy
      and costly quantum-chemical computation. However, we have tried to simulate the
      Raman spectrum of whole protein by adding the proportionate contribution of the
      Raman spectra of each amino acid present in this protein. In DFT calculations,
      only the contributions of disulphide bonds between cysteines are included but the
      contribution of the peptide and hydrogen bonds have not been considered. We have
      recorded the Raman spectra of bovine insulin using micro-Raman set up. The
      experimental spectrum is found to be very similar with the resultant simulated
      Raman spectrum with some exceptions. 

PMID- 24747860
TI  - New ruthenium(II) carbonyl complexes bearing disulfide Schiff base ligands and
      their applications as catalyst for some organic transformations.
AB  - Schiff base disulfide ligands (H2L(1-6)) were synthesized from the condensation
      of cystamine with salicylaldehyde(H2L(1)), 5-chlorosalicylaldehyde(H2L(2)), o
      vanillin(H2L(3)), 2-hydroxyacetophenone(H2L(4)), 3-methyl-2
      hydroxyacetophenone(H2L(5)), and 2-hydroxy-1-naphthaldehyde(H2L(6)). H2L(1-6)
      reacts with the ruthenium precursor complex [RuHCl(CO)(PPh3)3] in benzene giving
      rise to six new ruthenium(II) complexes of general formula [Ru(CO)L(1-6)].
      Characterization of the new complexes was carried out by using elemental and
      spectral (IR, UV-Vis, NMR ((1)H and (13)C) and Mass) techniques. An octahedral
      geometry was assigned for all the complexes based on the spectral data obtained.
      The catalytic efficiency of the new complexes in aldehyde to amide conversion in
      the presence of NaHCO3, N-alkylation of aniline in the presence of t-BuOK, and
      transfer hydrogenation of ketones in the presence of iPrOH/KOH reactions were
      studied. Furthermore, the effect of solvents and catalyst/substrate ratio on the
      catalytic aldehyde to amide conversion were also discussed. 

PMID- 24747861
TI  - SEIRA studies of uracil adsorbed on wet-chemically prepared gold nanoparticles
      film on glass substrate - effect of morphology of film.
AB  - Surface-enhanced infrared absorption (SEIRA) studies of uracil adsorbed on wet
      chemically prepared gold nanoparticles (AuNp) immobilized on silanised glass
      substrate were carried out using attenuated total reflectance-Fourier transform
      infrared (ATR-FTIR) spectroscopy. The deposition time dependent evolution of
      morphological changes in AuNp films and its influence on the SEIRA spectra of
      uracil were investigated. The morphological changes were examined by atomic force
      microscopy (AFM). The spectrum of uracil adsorbed on AuNp film obtained with 1/2
      an hour deposition time showed a clear enhancement than 2 and 4h deposition
      times. The small shift seen in SEIRA spectra indicates weak interaction of the
      molecules with AuNp film.

PMID- 24747862
TI  - Experimental and theoretical approach of photophysical properties of
      lanthanum(III) and erbium(III) complexes of tris(methoxymethyl)-5-oxine podant.
AB  - With the aim of evaluating the coordination behavior of a novel polydentate
      tripodal ligand, 5-[[3-[(8-hydroxy-5-quinolyl)methoxy]-2-[(8-hydroxy-5
      quinolyl)methoxymethyl]-2-methyl propoxy]methyl]quinolin-8-ol (TMOM5OX), towards
      La(III) and Er(III) metal ions, the detailed investigations of photophysical
      properties by theoritical and experimental (potentiometric, UV-visible and
      fluorescence spectrophotometry) methods were carried out. TMOM5OX has been found
      to form protonated complex [Ln(H4L)](4+) (Ln=La or Er) below pH 3.8, which
      consecutively deprotonates through one-proton processes with rise of pH. The
      formation constants (logbeta) of neutral complexes have been determined to be
      36.42 (LaL) and 35.76, 37.62 (for ErL and ErL2, respectively) and the pLn (pLn=
      log[Ln(3+)]) values of 24.6 and 27.1 for La(III) and Er(III) ions, respectively,
      calculated at pH 7.4, indicating TMOM5OX is a good lanthanide synthetic chelator.
      The absorption spectroscopy of these complexes show marked spectral variations
      due to characteristic lanthanide transitions, which support the use of TMOM5OX as
      a sensitive optical pH based sensor to detect Ln(III) metal ions in biological
      systems. In addition, these complexes have also been shown to exhibit strong
      green fluorescence allowing simultaneous sensing within the visible region under
      physiological pH in competitive medium for both La(III) and Er(III) ions. The
      intense fluorescence from these compounds were revealed to intermittently get
      quenched under acidic and basic conditions due to the photoinduced intramolecular
      electron transfer from excited 8-hydroxyquinoline (8-HQ) moiety to metal ion,
      just an opposite process. This renders these compounds the OFF-ON-OFF type of pH
      dependent fluorescent sensors. The complexes coordination geometries were
      optimized using the sparkle/PM6 model and the theoretical spectrophotometric
      studies were carried out in order to validate the experimental findings, based on
      ZINDO/S methodology at configuration interaction with single excitations (CIS)
      level. These results clearly attest for the efficacy of the theoretical models
      employed in all calculations and create new interesting possibilities for the
      design in-silico of novel and highly efficient lanthanide-organic frameworks. 

PMID- 24747863
TI  - Synthesis, characterization and spectroscopic investigations of novel nano multi
      metal oxide Co3O4.CeO2.ZnO.
AB  - A novel multi-metal nanocomposite, Co3O4.CeO2.ZnO has been prepared by co
      precipitation of their carbonates from aqueous solutions of the metal nitrates
      following calcining and annealing 5h at 450 degrees C and 10h at 950 degrees C.
      Co3O4.CeO2.ZnO has been characterized by XRD, SEM, EDS, IR and PL spectra. The
      crystallite size of the as-synthesized sample varies in the range of 9-33nm and
      those of the annealed sample in the range of 19-42nm. Emissions of Co3O4.CeO2.ZnO
      were observed in UV and visible region at different excitations. Excitation
      wavelength dependent PL behavior of Co3O4.CeO2.ZnO has been observed in acetone.
      This PL property is contrary to the well-known Kasha's rule of excitation
      wavelength dependence of emission spectrum. 

PMID- 24747864
TI  - Some new nano-structure zinc(II) coordination compounds of an imidazolidine
      Schiff base: spectral, thermal, antimicrobial properties and DNA interaction.
AB  - Some novel nano-sized structure zinc complexes of a new Schiff base ligand
      entitled as (3-nitro-benzylidene)-{2-[2-(3-nitro-phenyl)-imidazolidine-1-yl]
      ethyl}-amine(L) with general formula of ZnLX2 wherein X=Cl(-), Br(-), I(-), SCN(
      ) and N3(-) have been synthesized under ultrasonic conditions. The ligand and its
      complexes have been characterized by elemental analysis, molar conductance
      measurements, FT-IR, (1)H and (13)C NMR and UV-Visible spectroscopy. The
      resulting data from spectral investigation especially (1)H and (13)C NMR well
      confirmed formation of an imidazolidine ring in the ligand structure.
      Transmission electron microscopy (TEM) showed nano-size structures with average
      particle sizes of 21.80-78.10nm for the zinc(II) Schiff base complexes. The free
      Schiff base and its Zn(II) complexes have been screened in vitro both for
      antibacterial activity against some gram-positive and gram-negative bacteria and
      also for antifungal activity. The metal complexes were found to be more active
      than the free Schiff base ligand. The results showed that ZnL(N3)2 is the most
      effective inhibitor against Escherichia coli, Pseudomonas aereuguinosa,
      Staphylococcus aureus and Candida albicans while ZnLBr2 was found to be more
      effective against Bacillus subtillis than other compounds. Moreover, DNA cleavage
      potential of all compounds with plasmid DNA was investigated. The results showed
      that the ligand and ZnLCl2 complex cleave DNA more efficiently than others. In
      final, thermal analysis of ligand and its complexes revealed that they are
      decomposed via 2-3 thermal steps in the range of room temperature to 1000 degrees
      C. Furthermore some activation kinetic parameters such as A, E(*), DeltaH(*),
      DeltaS(*) and DeltaG(*) were calculated based on TG/DTA plots by use of coats -
      Redfern relation. Positive values of activation energy evaluated for the
      compounds confirmed the thermal stability of them. In addition to, the positive
      DeltaH(*), and DeltaG(*) values suggested endothermic character for the thermal
      decomposition steps. 

PMID- 24747865
TI  - Synthesis, crystal structure, photoluminescence, and DFT studies of bis(1,10
      phenanthroline)di(kappa(2)OO' nitrato)cadmium(II) [Cd(phen)2(NO3)2].
AB  - A cadmium 1,10-phenanthroline complex, [Cd(phen)2(NO3)2] has been synthesized by
      and its crystal structure determined. The compound is monoclinic, C2/c,
      a=11.5008(2), b=15.3523(2), c=13.2767(2)A, beta=103.610(2), Z=4. The compound is
      monomeric with a octacoordinate cadmium ion bonded to two bidentate 1,10
      phenanthroline molecules and two bidentate nitrate units. The metal ion is bis
      chelated by two N-heterocycles as well as by two nitrate ions in a distorted
      dodecahedral CdN4O4 coordination environment. The complex is thermally stable up
      to 110 degrees C. Photophysical investigation reveals that complex is luminescent
      in the solid state. The molecular geometry, harmonic vibrational frequencies and
      bonding features of complex [Cd(phen)2(NO3)2] in the ground-state have been
      calculated by using the density functional B3LYP method with 3-21G (d, p) as
      higher basis set. The calculated HOMO and LUMO energies show that charge transfer
      occurs within the molecule. Finally the calculation results were applied to
      simulate infrared spectrum of the title compound which show good agreement with
      observed spectrum. 

PMID- 24747866
TI  - Antibacterial, DNA interaction and cytotoxic activities of pendant-armed
      polyamine macrocyclic dinuclear nickel(II) and copper(II) complexes.
AB  - A series of dinuclear nickel(II) and copper(II) complexes (1-6) of hexaaza
      macrocycles of 2,6-diformyl-4-methylphenol with three different benzoyl pendant
      arms, 2,2'-benzoyliminodi(ethylamine) trihydrochloride (L), 2,2'-4
      nitrobenzoyliminodi(ethylamine) trihydrochloride (L') and 2,2'-3,5
      dinitrobenzoyliminodi(ethylamine) trihydrochloride (L") have been synthesized and
      characterized by spectral methods. The electrochemical studies of these complexes
      depict two irreversible one electron reduction processes around E(1)pc=-0.62 to 
      0.76 V and E(2)pc=-1.21 to -1.31, and nickel(II) complexes (1-3) exhibit two
      irreversible one electron oxidation processes around E(1)pa=1.08 to 1.14 V and
      E(2)pa=1.71 to 1.74 V. The room temperature magnetic moment values (MUeff, 1.52
      1.54 BM) indicate the presence of an antiferromagnetic interaction in the
      binuclear copper(II) complexes (4-6) which is also observed from the broad ESR
      spectra with a g value of 2.14-2.15. The synthesized complexes (1-6) were
      screened for their antibacterial activity. The results of DNA interaction studies
      indicate that the dinuclear complexes can bind to calf thymus DNA by
      intercalative mode and display efficient cleavage of plasmid DNA. Further, the
      cytotoxic activity of complexes 2, 5 and 6 on human liver adenocarcinoma (HepG2)
      cell line has been examined. Nuclear-chromatin cleavage has also been observed
      with PI staining and comet assays.

PMID- 24747867
TI  - Peginterferon alfa-2a with or without low-dose ribavirin for treatment-naive
      patients with hepatitis C virus genotype 2 receiving haemodialysis: a randomised
      trial.
AB  - OBJECTIVE: Data comparing the efficacy and safety of combination therapy with
      peginterferon plus low-dose ribavirin and peginterferon monotherapy in treatment
      naive haemodialysis patients with hepatitis C virus genotype 2 (HCV-2) infection
      are limited. DESIGN: In this randomised trial, 172 patients received 24 weeks of
      peginterferon alfa-2a 135 MUg/week plus ribavirin 200 mg/day (n=86) or
      peginterferon alfa-2a 135 MUg/week (n=86). The efficacy and safety endpoints were
      sustained virological response (SVR) rate and adverse event (AE)-related
      withdrawal rate. RESULTS: Compared with monotherapy, combination therapy had a
      greater SVR rate (74% vs 44%, relative risk (RR): 1.68 [95% CI 1.29 to 2.20];
      p<0.001). The beneficial effect of combination therapy was more pronounced in
      patients with baseline viral load >=800,000 IU/mL than those with baseline viral
      load <800,000 IU/mL (RR: 3.08 [95% CI 1.80 to 5.29] vs. RR: 1.11 [95% CI 0.83 to
      1.45]; interaction p=0.001). Patients receiving combination therapy were more
      likely to have a haemoglobin level of <8.5 g/dL (70% vs. 8%, risk difference
      (RD): 62% [95% CI 50% to 73%]; p<0.001) and required a higher dosage [mean:
      13,417 vs. 6667 IU/week, p=0.027] of epoetin beta to manage anaemia than those
      receiving monotherapy. The AE-related withdrawal rates were 6% and 3% in
      combination therapy and monotherapy groups, respectively (RD: 2% [95% CI -4% to
      9%]). CONCLUSIONS: In treatment-naive haemodialysis patients with HCV-2
      infection, combination therapy with peginterferon plus low-dose ribavirin
      achieved a greater SVR rate than peginterferon monotherapy. Most haemodialysis
      patients can tolerate combination therapy. TRIAL REGISTRATION NUMBER:
      ClinicalTrial.gov number, NCT00491244.

PMID- 24747868
TI  - Exhaled nitric oxide concentration and decompression-induced bubble formation: An
      index of decompression severity in humans?
AB  - INTRODUCTION: Previous studies have highlighted a decreased exhaled nitric oxide
      concentration (FE NO) in divers after hyperbaric exposure in a dry chamber or
      following a wet dive. The underlying mechanisms of this decrease remain however
      unknown. The aim of this study was to quantify the separate effects of
      submersion, hyperbaric hyperoxia exposure and decompression-induced bubble
      formation on FE NO after a wet dive. METHODS: Healthy experienced divers (n=31)
      were assigned to either (i) a group making a scuba-air dive (Air dive), (ii) a
      group with a shallow oxygen dive protocol (Oxygen dive) or (iii) a group making a
      deep dive breathing a trimix gas mixture (deep-dive). Bubble signals were graded
      with the KISS score. Before and after each dive FE NO values were measured using
      a hand-held electrochemical analyzer. RESULTS: There was no change in post-dive
      values of FE NO values (expressed in ppb=parts per billion) in the Air dive group
      (15.1 +/- 3.6 ppb vs. 14.3 +/- 4.7 ppb, n=9, p=0.32). There was a significant
      decrease in post-dive values of FE NO in the Oxygen dive group (15.6 +/- 6 ppb
      vs. 11.7 +/- 4.7 ppb, n=9, p=0.009). There was an even more pronounced decrease
      in the deep dive group (16.4 +/- 6.6 ppb vs. 9.4 +/- 3.5 ppb, n=13, p<0.001) and
      a significant correlation between KISS bubble score >0 (n=13) and percentage
      decrease in post-dive FE NO values (r=-0.53, p=0.03). DISCUSSION: Submersion and
      hyperbaric hyperoxia exposure cannot account entirely for these results
      suggesting the possibility that, in combination, one effect magnifies the other.
      A main finding of the present study is a significant relationship between
      reduction in exhaled NO concentration and dive-induced bubble formation. We
      postulate that exhaled NO concentration could be a useful index of decompression
      severity in healthy human divers.

PMID- 24747869
TI  - Enhanced chemopreventive effects of a hydrogen sulfide-releasing anti
      inflammatory drug (ATB-346) in experimental colorectal cancer.
AB  - Regular use of nonsteroidal anti-inflammatory drugs is associated with a
      significantly lower incidence of several types of cancer, particularly those
      affecting the gastrointestinal tract. However, the propensity of these drugs to
      cause ulcers and bleeding in the stomach and small intestine limits their utility
      for chemoprevention of cancer. In the present study, we evaluated the
      effectiveness of a novel hydrogen sulfide-releasing derivative of naproxen in
      reducing the incidence of pre-cancerous lesions (aberrant crypt foci) in mice
      treated with the carcinogen azoxymethane. Weekly administration of azoxymethane
      over a 4-week period resulted in formation of an average of ~50 aberrant crypt
      foci in the colon. Twice-daily treatment with naproxen at high doses
      significantly reduced the number of aberrant crypt foci. However, a significantly
      greater effect was observed with ATB-346 (H2S-releasing naproxen) and it was also
      effective at much lower doses, where naproxen was ineffective. The H2S-releasing
      moiety of ATB-346 did not significantly affect the number of aberrant crypt foci,
      suggesting that both the inhibition of cyclooxygenase activity and release of H2S
      were necessary for the enhanced chemopreventative effect. ATB-346 suppressed
      colonic prostaglandin synthesis and whole blood thromboxane synthesis as
      effectively as naproxen, but did not induce any gastrointestinal injury. These
      results demonstrate that ATB-346 exerts superior chemopreventive effects to those
      of naproxen, while sparing the gastrointestinal tract of the injury normally
      associated with use of the parent drug. ATB-346 may therefore be an attractive
      agent for chemoprevention of colon cancer, and possibly of cancers in other
      tissues. 

PMID- 24747870
TI  - GABAA receptor subunit composition and competition at synapses are tuned by GABAB
      receptor activity.
AB  - GABABRs have a well-established role in controlling neuronal excitability and
      presynaptic neurotransmitter release. We examined the role of GABABR activity in
      modulating the number and lateral diffusion of GABAARs at inhibitory synapses.
      Changes in diffusion of GABAARs at synapses were observed when subunit
      heterogeneity was taken into account. While alpha1-GABAARs were unaffected,
      alpha2- and alpha5-GABAARs showed inverse changes in enrichment and diffusion.
      The intracellular TM3-4 loop of alpha2 was sufficient to observe the changes in
      diffusion by GABABR activity, whereas the loop of alpha5 was not. The opposing
      effect on alpha2- and alpha5-GABAARs was caused by a competition between GABAARs
      for binding slots at synapses. Receptor immobilization by cross-linking revealed
      that alpha5-GABAAR trapping at synapses is regulated by modulation of alpha2
      GABAAR mobility. Finally, PKC activity was determined to be part of the signaling
      pathway through which GABABR activity modulates alpha2-GABAAR diffusion at
      synapses. These results outline a novel mechanism for tuning inhibitory
      transmission in a subunit-specific manner, and for the first time describe
      competition between GABAARs with different subunit compositions for binding slots
      at synapses. 

PMID- 24747871
TI  - Anandamide attenuates haloperidol-induced vacuous chewing movements in rats.
AB  - Antipsychotics may cause tardive dyskinesia in humans and orofacial dyskinesia in
      rodents. Although the dopaminergic system has been implicated in these movement
      disorders, which involve the basal ganglia, their underlying pathomechanisms
      remain unclear. CB1 cannabinoid receptors are highly expressed in the basal
      ganglia, and a potential role for endocannabinoids in the control of basal
      ganglia-related movement disorders has been proposed. Therefore, this study
      investigated whether CB1 receptors are involved in haloperidol-induced orofacial
      dyskinesia in rats. Adult male rats were treated for four weeks with haloperidol
      decanoate (38mg/kg, intramuscularly - i.m.). The effect of anandamide (6nmol,
      intracerebroventricularly - i.c.v.) and/or the CB1 receptor antagonist SR141716A
      (30MUg, i.c.v.) on haloperidol-induced vacuous chewing movements (VCMs) was
      assessed 28days after the start of the haloperidol treatment. Anandamide reversed
      haloperidol-induced VCMs; SR141716A (30MUg, i.c.v.) did not alter haloperidol
      induced VCM per se but prevented the effect of anandamide on VCM in rats. These
      results suggest that CB1 receptors may prevent haloperidol-induced VCMs in rats,
      implicating CB1 receptor-mediated cannabinoid signaling in orofacial dyskinesia. 

PMID- 24747872
TI  - The association of Restless Legs Syndrome with hypertension and cardiovascular
      disease.
AB  - Restless Legs Syndrome (RLS), is a sensory-motor neurological disorder that
      appears to be surprisingly common in the community. Periodic limb movements in
      sleep are typically encountered in more than 80% of RLS patients and comprise
      involuntary muscular jerks in the lower limbs, such as flexion of the knees or
      ankles.  Iron deficiency and dopaminergic neuronal dysfunction in the central
      nervous system are currently thought to be the likely pathophysiological
      culprits. There is evidence linking RLS to hypertension and cardiovascular
      disease. This short review will first present a synopsis of epidemiological,
      clinical and pathophysiological data concerning the syndrome, and then
      information on the possible links between RLS and cardiovascular disorders. 

PMID- 24747873
TI  - Who is talking in backward crosstalk? Disentangling response- from goal-conflict
      in dual-task performance.
AB  - Responses in the second of two subsequently performed tasks can speed up
      compatible responses in the temporally preceding first task. Such backward
      crosstalk effects (BCEs) represent a challenge to the assumption of serial
      processing in stage models of human information processing, because they indicate
      that certain features of the second response have to be represented before the
      first response is emitted. Which of these features are actually relevant for BCEs
      is an open question, even though identifying these features is important for
      understanding the nature of parallel and serial response selection processes in
      dual-task performance. Motivated by effect-based models of action control, we
      show in three experiments that the BCE to a considerable degree reflects features
      of intended action effects, although features of the response proper (or response
      associated kinesthetic feedback) also seem to play a role. These findings suggest
      that the codes of action effects (or action goals) can become activated
      simultaneously rather than serially, thereby creating BCEs. 

PMID- 24747874
TI  - Reliable and durable Golgi staining of brain tissue from human autopsies and
      experimental animals.
AB  - BACKGROUND: Golgi stains are notoriously capricious, particularly when applied to
      human brain. The well-known difficulties, which include complete failure of
      impregnation, patchy staining, unstable staining, and extensive crystalline
      deposits in superficial sections, have discouraged many from attempting to use
      these techniques. A reliable method that produces uniform impregnation in tissue
      from human autopsies and experimental animals is needed. NEW METHOD: The method
      described, "NeoGolgi", modifies previous Golgi-Cox protocols (Glaser and Van der
      Loos, 1981). Changes include: much longer time (>10 weeks) in Golgi solution,
      agitation on a slowly rocking platform, more gradual infiltration with Parlodion,
      more thorough removal of excess staining solution during embedding, and shorter
      exposure to ammonia after infiltration. RESULTS: The procedure has successfully
      stained over 220 consecutive frontal or hippocampal blocks from more than 175
      consecutive human autopsy cases. Dendritic spines are easily recognized, and
      background is clear, allowing examination of very thick (200 MUm) sections.
      Stained neurons are evenly distributed within cortical regions. The stain is
      stable for at least eight years. Most importantly, all stained neurons are
      apparently well-impregnated, eliminating ambiguity between pathology and poor
      impregnation that is inherent to other methods. COMPARISON WITH EXISTING METHODS:
      Most methods of Golgi staining are poorly predictable. They often fail
      completely, staining is patchy, and abnormal morphology is often
      indistinguishable from poor impregnation. "NeoGolgi" overcomes these problems.
      CONCLUSION: Starting with unfixed tissue, it is possible to obtain Golgi staining
      of predictably high quality in brains from human autopsies and experimental
      animals.

PMID- 24747875
TI  - Validation of a neuropathology score using quantitative methods to evaluate brain
      injury in a pig model of hypoxia ischaemia.
AB  - BACKGROUND: Neuropathological examination is the classic outcome measure in
      experimental studies of newborn brain injury to evaluate novel therapies. We have
      used a graded neuropathology score in an established global model of perinatal
      hypoxic-ischaemic (HI) injury. We wished to validate the score using cell
      counting in our model. NEW METHOD: 32 newborn pigs underwent a 45 min global HI
      insult then maintained at normothermia (NT, rectal temperature, Trectal 38.5 
      degrees C) for 72 h or mild total body hypothermia (HT, Trectal 37.0  degrees C)
      combined with selective head cooling for 48 h and subsequently maintained at NT
      for 24h before brain perfusion fixation. A perinatal pathologist scored
      haematoxylin and eosin stained 6 MUm histological sections for injury in the
      hippocampus and basal ganglia on a 9-step scale (0.0=no injury, 4.0=>75% injury).
      We counted the number of healthy neurons in the hippocampus CA1 region and
      putamen using morphological criteria in eight random, non-overlapping fields from
      representative sections. RESULTS: Healthy neuronal cell density correlated with
      neuropathology score in the hippocampus CA1 (r = -0.74) and in the putamen (r = 
      0.75) and both measures detected a difference between groups. The correlation
      coefficients were better for the NT compared to the HT group in both the
      hippocampus (r = -0.87 vs. -0.53) and putamen (r = -0.77 vs. -0.54). COMPARISON
      WITH EXISTING METHOD: We have validated a histological neuropathological scoring
      system in our model of perinatal HI by showing correlation between neuronal cell
      count and estimated injury. CONCLUSIONS: Our neuropathology score is a valid
      method to assess brain injury with good reproducibility and sensitivity.

PMID- 24747876
TI  - Improving reproducibility in toxicology.

PMID- 24747877
TI  - The cytoplasmic side of p53's oncosuppressive activities.
AB  - The tumor suppressor p53 is a transcription factor that in response to a plethora
      of stress stimuli activates a complex and context-dependent cellular response
      ultimately protecting genome integrity. In the last two decades, the discovery of
      cytoplasmic p53 localization has driven an intense research on its extra-nuclear
      functions. The ability to induce apoptosis acting directly at mitochondria and
      the related mechanisms of p53 localization and translocation in the cytoplasm and
      mitochondria have been dissected. However, recent works indicate the involvement
      of cytoplasmic p53 also in biological processes such as autophagy, metabolism,
      oxidative stress and drug response. This review will focus on the mechanisms of
      cytoplasmic p53 activation and the pathophysiological role of p53's transcription
      independent functions, highlighting possible therapeutic implications. 

PMID- 24747878
TI  - Parental perceptions of the impacts the built environment has on young children's
      health: a qualitative examination and lay assessment amongst residents in four
      Scottish communities.
AB  - The built environment is important for children's health and development.
      Qualitative research in four communities in Scotland explored with groups of
      parents of young children their lay perceptions of their local environment with
      specific reference to its impact upon their children's health. Valuing most
      strong supportive communities; good quality public spaces and social housing,
      parents' key concerns included anti-social behaviour, incivility and a range of
      locally-specific concerns. As knowledgeable key gatekeepers to children's use of
      home environments and public spaces, parent's qualitative lay input is important
      for the development of children's effective use of outdoor spaces and the built
      environment over the long term. 

PMID- 24747879
TI  - The need for harmonized structured documentation and chances of secondary use -
      results of a systematic analysis with automated form comparison for prostate and
      breast cancer.
AB  - INTRODUCTION: Medical documentation is a time-consuming task and there is a
      growing number of documentation requirements. In order to improve documentation,
      harmonization and standardization based on existing forms and medical concepts
      are needed. Systematic analysis of forms can contribute to standardization
      building upon new methods for automated comparison of forms. Objectives of this
      research are quantification and comparison of data elements for breast and
      prostate cancer to discover similarities, differences and reuse potential between
      documentation sets. In addition, common data elements for each entity should be
      identified by automated comparison of forms. MATERIALS AND METHODS: A collection
      of 57 forms regarding prostate and breast cancer from quality management,
      registries, clinical documentation of two university hospitals (Erlangen,
      Munster), research datasets, certification requirements and trial documentation
      were transformed into the Operational Data Model (ODM). These ODM-files were
      semantically enriched with concept codes and analyzed with the compareODM
      algorithm. Comparison results were aggregated and lists of common concepts were
      generated. Grid images, dendrograms and spider charts were used for illustration.
      RESULTS: Overall, 1008 data elements for prostate cancer and 1232 data elements
      for breast cancer were analyzed. Average routine documentation consists of 390
      data elements per disease entity and site. Comparisons of forms identified up to
      20 comparable data elements in cancer conference forms from both hospitals.
      Urology forms contain up to 53 comparable data elements with quality management
      and up to 21 with registry forms. Urology documentation of both hospitals
      contains up to 34 comparable items with international common data elements.
      Clinical documentation sets share up to 24 comparable data elements with trial
      documentation. Within clinical documentation administrative items are most common
      comparable items. Selected common medical concepts are contained in up to 16
      forms. DISCUSSION: The amount of documentation for cancer patients is enormous.
      There is an urgent need for standardized structured single source documentation.
      Semantic annotation is time-consuming, but enables automated comparison between
      different form types, hospital sites and even languages. This approach can help
      to identify common data elements in medical documentation. Standardization of
      forms and building up forms on the basis of coding systems is desirable. Several
      comparable data elements within the analyzed forms demonstrate the harmonization
      potential, which would enable better data reuse. CONCLUSION: Identifying common
      data elements in medical forms from different settings with systematic and
      automated form comparison is feasible.

PMID- 24747881
TI  - Effects of cis- and trans-unsaturated lipids on an interdigitated membrane.
AB  - The effects of adding cis- and trans-unsaturated lipid to a fully interdigitated
      membrane were examined using differential scanning calorimetry (DSC) and X-ray
      diffraction. A monofluorinated analog of 1,2-dipalmitoyl-sn-glycero-3
      phosphocholine (DPPC) was used as the interdigitated lipid. The single fluorine
      atom on the end of the sn-2 chain allows 1-palmitoyl-2-(16-fluoropalmitoyl)sn
      glycero-3-phosphocholine (F-DPPC) to spontaneously form the interdigitated gel
      phase (LbetaI) below the main transition temperature (Tm). The cis 1,2-dioleoyl
      sn-glycero-3-phosphocholine (DOPC) and equivalent trans lipid 1,2-dielaidoyl-sn
      glycero-3-phosphocholine (DEPC) are strongly disfavored to form the LbetaI phase.
      Wide-angle X-ray scattering (WAXS) data demonstrate that the unsaturated lipids
      progressively disrupt the intermolecular packing at higher concentrations. Small
      angle X-ray scattering (SAXS) data show that as the ratio of unsaturated lipid
      increases, the amount of interdigitated lipid decreases. The cis isomer is more
      disruptive and inhibits interdigitation more effectively than the trans isomer. 

PMID- 24747880
TI  - Rapid screening of HIV reverse transcriptase and integrase inhibitors.
AB  - Although a number of anti HIV drugs have been approved, there are still problems
      with toxicity and drug resistance. This demonstrates a need to identify new
      compounds that can inhibit infection by the common drug resistant HIV-1 strains
      with minimal toxicity. Here we describe an efficient assay that can be used to
      rapidly determine the cellular cytotoxicity and efficacy of a compound against WT
      and mutant viral strains. The desired target cell line is seeded in a 96-well
      plate and, after a 24 hr incubation, serially dilutions of the compounds to be
      tested are added. No further manipulations are necessary for cellular
      cytotoxicity assays; for anti HIV assays a predetermined amount of either a WT or
      drug resistant HIV-1 vector that expresses luciferase is added to the cells.
      Cytotoxicity is measured by using an ATP dependent luminescence assay and the
      impact of the compounds on infectivity is measured by determining the amount of
      luciferase in the presence or the absence of the putative inhibitors. This
      screening assay takes 4 days to complete and multiple compounds can be screened
      in parallel. Compounds are screened in triplicate and the data are normalized to
      the infectivity/ATP levels in absence of target compounds. This technique
      provides a quick and accurate measurement of the efficacy and toxicity of
      potential anti HIV compounds. 

PMID- 24747882
TI  - SNARE zippering and synaptic strength.
AB  - Synapses vary widely in the probability of neurotransmitter release. We tested
      the hypothesis that the zippered state of the trans-SNARE (Soluble N
      ethylmaleimide-sensitive factor Attachment protein REceptor) complex determines
      initial release probability. We tested this hypothesis at phasic and tonic
      synapses which differ by 100-1000-fold in neurotransmitter release probability.
      We injected, presynaptically, three Clostridial neurotoxins which bind and cleave
      at different sites on VAMP to determine whether these sites were occluded by the
      zippering of the SNARE complex or open to proteolytic attack. Under low
      stimulation conditions, the catalytic light-chain fragment of botulinum B (BoNT/B
      LC) inhibited evoked release at both phasic and tonic synapses and cleaved VAMP;
      however, neither BoNT/D-LC nor tetanus neurotoxin (TeNT-LC) were effective in
      these conditions. The susceptibility of VAMP to only BoNT/B-LC indicated that
      SNARE complexes at both phasic and tonic synapses were partially zippered only at
      the N-terminal end to approximately the zero-layer with the C-terminal end
      exposed under resting state. Therefore, the existence of the same partially
      zippered state of the trans-SNARE complex at both phasic and tonic synapses
      indicates that release probability is not determined solely by the zippered state
      of the trans-SNARE complex at least to the zero-layer. 

PMID- 24747883
TI  - Context-dependent responses to neighbours and strangers in wild European rabbits
      (Oryctolagus cuniculus).
AB  - Territorial animals defend their territories against intruders. The level of
      aggression directed to intruders depends on the familiarity and/or the relative
      threat they pose, and it could be modified by the context of the interaction. We
      explored in a wild social mammal, the European rabbit (Oryctolagus cuniculus),
      whether residents responded more aggressively to strangers or to neighbours (dear
      enemy or nasty neighbour effects, respectively). We simulated the intrusion of
      neighbours or strangers in different parts of the territory of wild European
      rabbits in a suburban area in central Spain. For that, we placed faecal pellets
      of neighbouring or stranger rabbits in the territory of 5 rabbit colonies.
      Resident rabbits counter-marked preferably the odour stations with stranger
      odour, compared to the ones with neighbour odour, and they did not make a
      difference between neighbour and a non-odour control stimuli. The results suggest
      that rabbits show a dear enemy effect. However, repeated intrusions escalated the
      responses of rabbits towards neighbours. The location within the territory or the
      sex of the stranger did not affect the level of response. We conclude that in
      rabbits the relative threat posed by the intruder triggers the intensity of the
      interaction. 

PMID- 24747884
TI  - Concerns regarding a lack of nutrient deficiency assessment in early development.

PMID- 24747886
TI  - A method to study the impact of chemically-induced ovarian failure on exercise
      capacity and cardiac adaptation in mice.
AB  - The risk of cardiovascular disease (CVD) increases in post-menopausal women, yet,
      the role of exercise, as a preventative measure for CVD risk in post-menopausal
      women has not been adequately studied. Accordingly, we investigated the impact of
      voluntary cage-wheel exercise and forced treadmill exercise on cardiac adaptation
      in menopausal mice. The most commonly used inducible model for mimicking
      menopause in women is the ovariectomized (OVX) rodent. However, the OVX model has
      a few dissimilarities from menopause in humans. In this study, we administered 4
      vinylcyclohexene diepoxide (VCD) to female mice, which accelerates ovarian
      failure as an alternative menopause model to study the impact of exercise in
      menopausal mice. VCD selectively accelerates the loss of primary and primordial
      follicles resulting in an endocrine state that closely mimics the natural
      progression from pre- to peri- to post-menopause in humans. To determine the
      impact of exercise on exercise capacity and cardiac adaptation in VCD-treated
      female mice, two methods were used. First, we exposed a group of VCD-treated and
      untreated mice to a voluntary cage wheel. Second, we used forced treadmill
      exercise to determine exercise capacity in a separate group VCD-treated and
      untreated mice measured as a tolerance to exercise intensity and endurance. 

PMID- 24747887
TI  - Infection of keratinocytes with Trichophytum rubrum induces epidermal growth
      factor-dependent RNase 7 and human beta-defensin-3 expression.
AB  - Human keratinocytes are able to express various antimicrobial peptides (AMP) to
      protect the skin from exaggerated microbial colonization and infection. Recently,
      in vitro growth-inhibiting activity of the skin-derived AMP psoriasin, RNase 7
      and human beta-defensin (hBD)-2 against dermatophytes such as Trichophyton (T.)
      rubrum have been reported. To evaluate whether keratinocytes are able to respond
      to T. rubrum infection by an induced expression of AMP we exposed primary
      keratinocytes to living conidia of T. rubrum. This led to conidia germination and
      mycelial growth which was paralleled by a strong gene induction of the skin
      derived AMP RNase 7 and hBD-3. Gene expression of the AMP psoriasin (S100A7) and
      hBD-2 were only slightly induced. The T. rubrum-mediated RNase 7 gene induction
      was accompanied by increased secretion of RNase 7. Parallel treatment of the
      keratinocytes with T. rubrum and the cytokine combination IL-17A/IFN-gamma
      resulted in synergistic induction of RNase 7 and hBD-3 expression. Since patients
      receiving therapy by inhibition of the epidermal growth factor receptor (EGFR)
      more often suffer from dermatophytoses we investigated whether EGFR may be
      involved in the T. rubrum-mediated RNase 7 and hBD-3 induction. Primary
      keratinocytes incubated with an EGFR blocking antibody as well as with the EGFR
      antagonist AG1478 showed a significantly diminished RNase 7 and hBD-3 induction
      upon exposure of the keratinocytes to T. rubrum indicating that EGFR is involved
      in the T. rubrum-mediated induction of RNase 7 and hBD-3. The growth of T. rubrum
      in vitro was inhibited by hBD-3 in a dose-dependent manner suggesting that hBD-3
      may contribute to cutaneous innate defense against T. rubrum. Taken together our
      data indicate that keratinocytes are able to initiate a fast defense response
      towards T. rubrum by the increased expression of AMP active against T. rubrum. A
      dysregulation of AMP may contribute to chronic and recurring dermatophytoses. 

PMID- 24747888
TI  - In situ evaluation of Paenibacillus alvei in reducing carriage of Salmonella
      enterica serovar Newport on whole tomato plants.
AB  - Recently, tomatoes have been implicated as a primary vehicle in food-borne
      outbreaks of Salmonella enterica serovar Newport and other Salmonella serovars.
      Long-term intervention measures to reduce Salmonella prevalence on tomatoes
      remain elusive for growing and postharvest environments. A naturally occurring
      bacterium identified by 16S rRNA gene sequencing as Paenibacillus alvei was
      isolated epiphytically from plants native to the Virginia Eastern Shore tomato
      growing region. After initial antimicrobial activity screening against Salmonella
      and 10 other bacterial pathogens associated with the human food supply, strain TS
      15 was further used to challenge an attenuated strain of S. Newport on inoculated
      fruits, leaves, and blossoms of tomato plants in an insect-screened high tunnel
      with a split-plot design. Survival of Salmonella after inoculation was measured
      for groups with and those without the antagonist at days 0, 1, 2, and 3 and
      either day 5 for blossoms or day 6 for fruits and leaves. Strain TS-15 exhibited
      broad-range antimicrobial activity against both major food-borne pathogens and
      major bacterial phytopathogens of tomato. After P. alvei strain TS-15 was applied
      onto the fruits, leaves, and blossoms of tomato plants, the concentration of S.
      Newport declined significantly (P <= 0.05) compared with controls. Astonishingly,
      >90% of the plants had no detectable levels of Salmonella by day 5 for blossoms.
      The naturally occurring antagonist strain TS-15 is highly effective in reducing
      the carriage of Salmonella Newport on whole tomato plants. The application of P.
      alvei strain TS-15 is a promising approach for reducing the risk of Salmonella
      contamination during tomato production. 

PMID- 24747889
TI  - High-efficiency scarless genetic modification in Escherichia coli by using lambda
      red recombination and I-SceI cleavage.
AB  - Genetic modifications of bacterial chromosomes are important for both fundamental
      and applied research. In this study, we developed an efficient, easy-to-use
      system for genetic modification of the Escherichia coli chromosome, a two-plasmid
      method involving lambda Red (lambda-Red) recombination and I-SceI cleavage. An
      intermediate strain is generated by integration of a resistance marker gene(s)
      and I-SceI recognition sites in or near the target gene locus, using lambda-Red
      PCR targeting. The intermediate strain is transformed with a donor plasmid
      carrying the target gene fragment with the desired modification flanked by I-SceI
      recognition sites, together with a bifunctional helper plasmid for lambda-Red
      recombination and I-SceI endonuclease. I-SceI cleavage of the chromosome and the
      donor plasmid allows lambda-Red recombination between chromosomal breaks and
      linear double-stranded DNA from the donor plasmid. Genetic modifications are
      introduced into the chromosome, and the placement of the I-SceI sites determines
      the nature of the recombination and the modification. This method was
      successfully used for cadA knockout, gdhA knock-in, seamless deletion of pepD,
      site-directed mutagenesis of the essential metK gene, and replacement of metK
      with the Rickettsia S-adenosylmethionine transporter gene. This effective method
      can be used with both essential and nonessential gene modifications and will
      benefit basic and applied genetic research. 

PMID- 24747890
TI  - Genomic features of a bumble bee symbiont reflect its host environment.
AB  - Here, we report the genome of one gammaproteobacterial member of the gut
      microbiota, for which we propose the name "Candidatus Schmidhempelia bombi," that
      was inadvertently sequenced alongside the genome of its host, the bumble bee,
      Bombus impatiens. This symbiont is a member of the recently described bacterial
      order Orbales, which has been collected from the guts of diverse insect species;
      however, "Ca. Schmidhempelia" has been identified exclusively with bumble bees.
      Metabolic reconstruction reveals that "Ca. Schmidhempelia" lacks many genes for a
      functioning NADH dehydrogenase I, all genes for the high-oxygen cytochrome o, and
      most genes in the tricarboxylic acid (TCA) cycle. "Ca. Schmidhempelia" has
      retained NADH dehydrogenase II, the low-oxygen specific cytochrome bd, anaerobic
      nitrate respiration, mixed-acid fermentation pathways, and citrate fermentation,
      which may be important for survival in low-oxygen or anaerobic environments found
      in the bee hindgut. Additionally, a type 6 secretion system, a Flp pilus, and
      many antibiotic/multidrug transporters suggest complex interactions with its host
      and other gut commensals or pathogens. This genome has signatures of reduction
      (2.0 megabase pairs) and rearrangement, as previously observed for genomes of
      host-associated bacteria. A survey of wild and laboratory B. impatiens revealed
      that "Ca. Schmidhempelia" is present in 90% of individuals and, therefore, may
      provide benefits to its host. 

PMID- 24747891
TI  - A novel angular dioxygenase gene cluster encoding 3-phenoxybenzoate 1',2'
      dioxygenase in Sphingobium wenxiniae JZ-1.
AB  - Sphingobium wenxiniae JZ-1 utilizes a wide range of pyrethroids and their
      metabolic product, 3-phenoxybenzoate, as sources of carbon and energy. A mutant
      JZ-1 strain, MJZ-1, defective in the degradation of 3-phenoxybenzoate was
      obtained by successive streaking on LB agar. Comparison of the draft genomes of
      strains JZ-1 and MJZ-1 revealed that a 29,366-bp DNA fragment containing a
      putative angular dioxygenase gene cluster (pbaA1A2B) is missing in strain MJZ-1.
      PbaA1, PbaA2, and PbaB share 65%, 52%, and 10% identity with the corresponding
      alpha and beta subunits and the ferredoxin component of dioxin dioxygenase from
      Sphingomonas wittichii RW1, respectively. Complementation of pbaA1A2B in strain
      MJZ-1 resulted in the active 3-phenoxybenzoate 1',2'-dioxygenase, but the enzyme
      activity in Escherichia coli was achieved only through the coexpression of
      pbaA1A2B and a glutathione reductase (GR)-type reductase gene, pbaC, indicating
      that the 3-phenoxybenzoate 1',2'-dioxygenase belongs to a type IV Rieske non-heme
      iron aromatic ring-hydroxylating oxygenase system consisting of a hetero
      oligomeric oxygenase, a [2Fe-2S]-type ferredoxin, and a GR-type reductase. The
      pbaC gene is not located in the immediate vicinity of pbaA1A2B. 3-Phenoxybenzoate
      1',2'-dioxygenase catalyzes the hydroxylation in the 1' and 2' positions of the
      benzene moiety of 3-phenoxybenzoate, yielding 3-hydroxybenzoate and catechol.
      Transcription of pbaA1A2B and pbaC was induced by 3-phenoxybenzoate, but the
      transcriptional level of pbaC was far less than that of pbaA1A2B, implying the
      possibility that PbaC may not be the only reductase that can physiologically
      transfer electrons to PbaA1A2B in strain JZ-1. Some GR-type reductases from other
      sphingomonad strains could also transfer electrons to PbaA1A2B, suggesting that
      PbaA1A2B has a low specificity for reductase. 

PMID- 24747892
TI  - Differing populations of endemic bacteriophages in cattle shedding high and low
      numbers of Escherichia coli O157:H7 bacteria in feces.
AB  - The objectives of this study were to identify endemic bacteriophages (phages) in
      the feedlot environment and determine relationships of these phages to
      Escherichia coli O157:H7 from cattle shedding high and low numbers of naturally
      occurring E. coli O157:H7. Angus crossbred steers were purchased from a southern
      Alberta (Canada) feedlot where cattle excreting >= 10(4) CFU . g(-1) of E. coli
      O157:H7 in feces at a single time point were identified as supershedders (SS; n =
      6), and cattle excreting <10(4) CFU . g(-1) of feces were identified as low
      shedders (LS; n = 5). Fecal pats or fecal grabs were collected daily from
      individual cattle for 5 weeks. E. coli O157:H7 in feces was detected by
      immunomagnetic separation and enumerated by direct plating, and phages were
      isolated using short- and overnight-enrichment methods. The total prevalence of
      E. coli O157:H7 isolated from feces was 14.4% and did not differ between LS and
      SS (P = 0.972). The total prevalence of phages was higher in the LS group (20.9%)
      than in the SS group (8.3%; P = 0.01). Based on genome size estimated by pulsed
      field gel electrophoresis and morphology determined by transmission electron
      microscopy, T4- and O1-like phages of Myoviridae and T1-like phage of
      Siphoviridae were isolated. Compared to T1- and O1-like phages, T4-like phages
      exhibited a broad host range and strong lytic capability when targeting E. coli
      O157:H7. Moreover, the T4-like phages were more frequently isolated from feces of
      LS than SS, suggesting that endemic phages may impact the shedding dynamics of E.
      coli O157:H7 in cattle.

PMID- 24747893
TI  - Stress response and adaptation of Listeria monocytogenes 08-5923 exposed to a
      sublethal dose of carnocyclin A.
AB  - Carnocyclin A (CCLA) is an antimicrobial peptide produced by Carnobacterium
      maltaromaticum ATCC PTA-5313, which can be used to control the growth of Listeria
      monocytogenes in ready-to-eat meat products. The aim of this research was to
      elucidate the cellular responses of L. monocytogenes 08-5923 exposed to a
      sublethal dose of CCLA. Microarray, quantitative reverse transcription-PCR,
      tandem mass spectrometry, and electron microscopy were used to investigate the
      alteration in gene expression, protein production, and morphological changes in
      cells of Listeria following treatment with CCLA. The genes involved in metabolism
      (baiE, trn, and pykA), cell wall synthesis (murZ and dacB2), and cell division
      (clpE and divIVA) were upregulated following a 15-min exposure to CCLA as a
      result of stress responses. Genes involved in cell division, cell wall synthesis,
      flagellar synthesis, and metabolism were downregulated after 4 h as a result of
      adaptation. Analysis of total soluble proteins confirmed the downregulation of
      pykA and gnd after 4 h of exposure to CCLA. The absence of flagella was observed
      in L. monocytogenes following 30 h of exposure to CCLA. A sublethal dose of CCLA
      induced adaptation in L. monocytogenes 08-5923 by inhibition of expression of
      genes and proteins critical for synthesis of cell wall structures and maintaining
      metabolic functions. Both the mannose- and cellobiose-specific phosphotransferase
      systems could be targets for CCLA. 

PMID- 24747894
TI  - From metagenomics to pure culture: isolation and characterization of the
      moderately halophilic bacterium Spiribacter salinus gen. nov., sp. nov.
AB  - Recent metagenomic studies on saltern ponds with intermediate salinities have
      determined that their microbial communities are dominated by both Euryarchaeota
      and halophilic bacteria, with a gammaproteobacterium closely related to the
      genera Alkalilimnicola and Arhodomonas being one of the most predominant
      microorganisms, making up to 15% of the total prokaryotic population. Here we
      used several strategies and culture media in order to isolate this organism in
      pure culture. We report the isolation and taxonomic characterization of this new,
      never before cultured microorganism, designated M19-40(T), isolated from a
      saltern located in Isla Cristina, Spain, using a medium with a mixture of 15%
      salts, yeast extract, and pyruvic acid as the carbon source. Morphologically
      small curved cells (young cultures) with a tendency to form long spiral cells in
      older cultures were observed in pure cultures. The organism is a Gram-negative,
      nonmotile bacterium that is strictly aerobic, non-endospore forming,
      heterotrophic, and moderately halophilic, and it is able to grow at 10 to 25%
      (wt/vol) NaCl, with optimal growth occurring at 15% (wt/vol) NaCl. Phylogenetic
      analysis based on 16S rRNA gene sequence comparison showed that strain M19-40(T)
      has a low similarity with other previously described bacteria and shows the
      closest phylogenetic similarity with species of the genera Alkalilimnicola (94.9
      to 94.5%), Alkalispirillum (94.3%), and Arhodomonas (93.9%) within the family
      Ectothiorhodospiraceae. The phenotypic, genotypic, and chemotaxonomic features of
      this new bacterium showed that it constitutes a new genus and species, for which
      the name Spiribacter salinus gen. nov., sp. nov., is proposed, with strain M19
      40(T) (= CECT 8282(T) = IBRC-M 10768(T) = LMG 27464(T)) being the type strain. 

PMID- 24747895
TI  - Use of silicate minerals for pH control during reductive dechlorination of
      chloroethenes in batch cultures of different microbial consortia.
AB  - In chloroethene-contaminated sites undergoing in situ bioremediation, groundwater
      acidification is a frequent problem in the source zone, and buffering strategies
      have to be implemented to maintain the pH in the neutral range. An alternative to
      conventional soluble buffers is silicate mineral particles as a long-term source
      of alkalinity. In previous studies, the buffering potentials of these minerals
      have been evaluated based on abiotic dissolution tests and geochemical modeling.
      In the present study, the buffering potentials of four silicate minerals
      (andradite, diopside, fayalite, and forsterite) were tested in batch cultures
      amended with tetrachloroethene (PCE) and inoculated with different organohalide
      respiring consortia. Another objective of this study was to determine the
      influence of pH on the different steps of PCE dechlorination. The consortia
      showed significant differences in sensitivities toward acidic pH for the
      different dechlorination steps. Molecular analysis indicated that Dehalococcoides
      spp. that were present in all consortia were the most pH-sensitive organohalide
      respiring guild members compared to Sulfurospirillum spp. and Dehalobacter spp.
      In batch cultures with silicate mineral particles as pH-buffering agents, all
      four minerals tested were able to maintain the pH in the appropriate range for
      reductive dechlorination of chloroethenes. However, complete dechlorination to
      ethene was observed only with forsterite, diopside, and fayalite. Dissolution of
      andradite increased the redox potential and did not allow dechlorination. With
      forsterite, diopside, and fayalite, dechlorination to ethene was observed but at
      much lower rates for the last two dechlorination steps than with the positive
      control. This indicated an inhibition effect of silicate minerals and/or their
      dissolution products on reductive dechlorination of cis-dichloroethene and vinyl
      chloride. Hence, despite the proven pH-buffering potential of silicate minerals,
      compatibility with the bacterial community involved in in situ bioremediation has
      to be carefully evaluated prior to their use for pH control at a specific site. 

PMID- 24747896
TI  - Microscopy, culture, and quantitative real-time PCR examination confirm
      internalization of mycobacteria in plants.
AB  - The environment is a reservoir of nontuberculous mycobacteria and is considered a
      source of infection for animals and humans. Mycobacteria can persist in different
      types of environments for a relatively long time. We have studied their possible
      internalization into plant tissue through intact, as well as damaged, root
      systems of different types of plants grown in vitro and under field conditions.
      The substrate into which plants were seeded was previously contaminated with
      different strains of Mycobacterium avium (10(8) to 10(10) cells/g of soil) and
      feces from animals with paratuberculosis. We detected M. avium subsp. avium,
      hominissuis, and paratuberculosis in the stems and leaves of the plants by both
      culture and real-time quantitative PCR. The presence of mycobacteria in the plant
      tissues was confirmed by microscopy. The concentration of mycobacteria found
      inside plant tissue was several orders of magnitude lower (up to 10(4) cells/g of
      tissue) than the initial concentration of mycobacteria present in the culture
      medium or substrate. These findings led us to the hypothesis that plants may play
      a role in the spread and transmission of mycobacteria to other organisms in the
      environment. 

PMID- 24747897
TI  - The pattern of change in the abundances of specific bacterioplankton groups is
      consistent across different nutrient-enriched habitats in Crete.
AB  - A common source of disturbance for coastal aquatic habitats is nutrient
      enrichment through anthropogenic activities. Although the water column
      bacterioplankton communities in these environments have been characterized in
      some cases, changes in alpha-diversity and/or the abundances of specific
      taxonomic groups across enriched habitats remain unclear. Here, we investigated
      the bacterial community changes at three different nutrient-enriched and adjacent
      undisturbed habitats along the north coast of Crete, Greece: a fish farm, a
      closed bay within a town with low water renewal rates, and a city port where the
      level of nutrient enrichment and the trophic status of the habitat were
      different. Even though changes in alpha-diversity were different at each site, we
      observed across the sites a common change pattern accounting for most of the
      community variation for five of the most abundant bacterial groups: a decrease in
      the abundance of the Pelagibacteraceae and SAR86 and an increase in the abundance
      of the Alteromonadaceae, Rhodobacteraceae, and Cryomorphaceae in the impacted
      sites. The abundances of the groups that increased and decreased in the impacted
      sites were significantly correlated (positively and negatively, respectively)
      with the total heterotrophic bacterial counts and the concentrations of dissolved
      organic carbon and/or dissolved nitrogen and chlorophyll alpha, indicating that
      the common change pattern was associated with nutrient enrichment. Our results
      provide an in situ indication concerning the association of specific
      bacterioplankton groups with nutrient enrichment. These groups could potentially
      be used as indicators for nutrient enrichment if the pattern is confirmed over a
      broader spatial and temporal scale by future studies. 

PMID- 24747898
TI  - Deciphering the effect of the different N-glycosylation sites on the secretion,
      activity, and stability of cellobiohydrolase I from Trichoderma reesei.
AB  - N-linked glycosylation modulates and diversifies the structures and functions of
      the eukaryotic proteome through both intrinsic and extrinsic effects on proteins.
      We investigated the significance of the three N-linked glycans on the catalytic
      domain of cellobiohydrolase I (CBH1) from the filamentous fungus Trichoderma
      reesei in its secretion and activity. While the removal of one or two N
      glycosylation sites hardly affected the extracellular secretion of CBH1,
      eliminating all of the glycosylation sites did induce expression of the unfolded
      protein response (UPR) target genes, and secretion of this CBH1 variant was
      severely compromised in a calnexin gene deletion strain. Further characterization
      of the purified CBH1 variants showed that, compared to Asn270, the thermal
      reactivity of CBH1 was significantly decreased by removal of either Asn45 or
      Asn384 glycosylation site during the catalyzed hydrolysis of soluble substrate.
      Combinatorial loss of these two N-linked glycans further exacerbated the
      temperature-dependent inactivation. In contrast, this thermal labile property was
      less severe when hydrolyzing insoluble cellulose. Analysis of the structural
      integrity of CBH1 variants revealed that removal of N-glycosylation at Asn384 had
      a more pronounced effect on the integrity of regular secondary structure compared
      to the loss of Asn45 or Asn270. These data implicate differential roles of N
      glycosylation modifications in contributing to the stability of specific
      functional regions of CBH1 and highlight the potential of improving the
      thermostability of CBH1 by tuning proper interactions between glycans and
      functional residues. 

PMID- 24747899
TI  - Triggering respirofermentative metabolism in the crabtree-negative yeast Pichia
      guilliermondii by disrupting the CAT8 gene.
AB  - Pichia guilliermondii is a Crabtree-negative yeast that does not normally exhibit
      respirofermentative metabolism under aerobic conditions, and methods to trigger
      this metabolism may have applications for physiological study and industrial
      applications. In the present study, CAT8, which encodes a putative global
      transcriptional activator, was disrupted in P. guilliermondii. This yeast's
      ethanol titer increased by >20-fold compared to the wild type (WT) during aerobic
      fermentation using glucose. A comparative transcriptional analysis indicated that
      the expression of genes in the tricarboxylic acid cycle and respiratory chain was
      repressed in the CAT8-disrupted (DeltaCAT8) strain, while the fermentative
      pathway genes were significantly upregulated. The respiratory activities in the
      DeltaCAT8 strain, indicated by the specific oxygen uptake rate and respiratory
      state value, decreased to one-half and one-third of the WT values, respectively.
      In addition, the expression of HAP4, a transcriptional respiratory activator, was
      significantly repressed in the DeltaCAT8 strain. Through disruption of HAP4, the
      ethanol production of P. guilliermondii was also increased, but the yield and
      titer were lower than that in the DeltaCAT8 strain. A further transcriptional
      comparison between DeltaCAT8 and DeltaHAP4 strains suggested a more comprehensive
      reprogramming function of Cat8 in the central metabolic pathways. These results
      indicated the important role of CAT8 in regulating the glucose metabolism of P.
      guilliermondii and that the regulation was partially mediated by repressing HAP4.
      The strategy proposed here might be applicable to improve the aerobic
      fermentation capacity of other Crabtree-negative yeasts. 

PMID- 24747900
TI  - Promotion of endodontic lesions in rats by a novel extraradicular biofilm model
      using obturation materials.
AB  - Although extraradicular biofilm formation is related to refractory periapical
      periodontitis, the mechanism of extraradicular biofilm development, as well as
      its effect on periapical lesions, is unknown. Therefore, we aimed to develop an
      in vivo extraradicular biofilm model in rats and to identify and quantify
      extraradicular biofilm-forming bacteria while investigating the effect of
      extraradicular biofilms on periapical lesions. Periapical lesions were induced by
      exposing the pulpal tissue of the mandibular first molars of male Wistar rats to
      their oral environment. Four weeks later, gutta-percha points were excessively
      inserted into the mesial root canals of the right first molars (experimental
      sites) but not the left first molars (control sites). After 6 and 8 weeks of pulp
      exposure, the presence of extraradicular biofilms was confirmed
      histomorphologically, and biofilm-forming bacteria were identified by using
      classical culture methods. The biofilms were observed in the extraradicular area
      of the experimental sites. Similar species were detected both inside and outside
      the root canals. The bacterial count, quantified by real-time PCR assays, in the
      extraradicular area gradually increased in the experimental sites until 20 weeks
      after pulp exposure. After 8 weeks of pulp exposure, the periapical lesion volume
      that was measured by micro-computed tomography was significantly larger in the
      experimental sites than in the control sites (P < 0.05 by Welch's t test). These
      results suggest that we developed an extraradicular biofilm model in rats and
      that extraradicular biofilms affect developing periapical lesions. 

PMID- 24747901
TI  - High genetic diversity among strains of the unindustrialized lactic acid
      bacterium Carnobacterium maltaromaticum in dairy products as revealed by
      multilocus sequence typing.
AB  - Dairy products are colonized with three main classes of lactic acid bacteria
      (LAB): opportunistic bacteria, traditional starters, and industrial starters.
      Most of the population structure studies were previously performed with LAB
      species belonging to these three classes and give interesting knowledge about the
      population structure of LAB at the stage where they are already industrialized.
      However, these studies give little information about the population structure of
      LAB prior their use as an industrial starter. Carnobacterium maltaromaticum is a
      LAB colonizing diverse environments, including dairy products. Since this
      bacterium was discovered relatively recently, it is not yet commercialized as an
      industrial starter, which makes C. maltaromaticum an interesting model for the
      study of unindustrialized LAB population structure in dairy products. A
      multilocus sequence typing scheme based on an analysis of fragments of the genes
      dapE, ddlA, glpQ, ilvE, pyc, pyrE, and leuS was applied to a collection of 47
      strains, including 28 strains isolated from dairy products. The scheme allowed
      detecting 36 sequence types with a discriminatory index of 0.98. The whole
      population was clustered in four deeply branched lineages, in which the dairy
      strains were spread. Moreover, the dairy strains could exhibit a high diversity
      within these lineages, leading to an overall dairy population with a diversity
      level as high as that of the nondairy population. These results are in agreement
      with the hypothesis according to which the industrialization of LAB leads to a
      diversity reduction in dairy products. 

PMID- 24747902
TI  - Biotic interactions and sunlight affect persistence of fecal indicator bacteria
      and microbial source tracking genetic markers in the upper Mississippi river.
AB  - The sanitary quality of recreational waters that may be impacted by sewage is
      assessed by enumerating fecal indicator bacteria (FIB) (Escherichia coli and
      enterococci); these organisms are found in the gastrointestinal tracts of humans
      and many other animals, and hence their presence provides no information about
      the pollution source. Microbial source tracking (MST) methods can discriminate
      between different pollution sources, providing critical information to water
      quality managers, but relatively little is known about factors influencing the
      decay of FIB and MST genetic markers following release into aquatic environments.
      An in situ mesocosm was deployed at a temperate recreational beach in the
      Mississippi River to evaluate the effects of ambient sunlight and biotic
      interactions (predation, competition, and viral lysis) on the decay of culture
      based FIB, as well as molecularly based FIB (Entero1a and GenBac3) and human
      associated MST genetic markers (HF183 and HumM2) measured by quantitative real
      time PCR (qPCR). In general, culturable FIB decayed the fastest, while
      molecularly based FIB and human-associated genetic markers decayed more slowly.
      There was a strong correlation between the decay of molecularly based FIB and
      that of human-associated genetic markers (r(2), 0.96 to 0.98; P < 0.0001) but not
      between culturable FIB and any qPCR measurement. Overall, exposure to ambient
      sunlight may be an important factor in the early-stage decay dynamics but
      generally was not after continued exposure (i.e., after 120 h), when biotic
      interactions tended to be the only/major influential determinant of persistence. 

PMID- 24747903
TI  - Variables influencing extraction of nucleic acids from microbial plankton
      (viruses, bacteria, and protists) collected on nanoporous aluminum oxide filters.
AB  - Anodic aluminum oxide (AAO) filters have high porosity and can be manufactured
      with a pore size that is small enough to quantitatively capture viruses. These
      properties make the filters potentially useful for harvesting total microbial
      communities from water samples for molecular analyses, but their performance for
      nucleic acid extraction has not been systematically or quantitatively evaluated.
      In this study, we characterized the flux of water through commercially produced
      nanoporous (0.02 MUm) AAO filters (Anotop; Whatman) and used isolates (a virus, a
      bacterium, and a protist) and natural seawater samples to test variables that we
      expected would influence the efficiency with which nucleic acids are recovered
      from the filters. Extraction chemistry had a significant effect on DNA yield, and
      back flushing the filters during extraction was found to improve yields of high
      molecular-weight DNA. Using the back-flush protocol, the mass of DNA recovered
      from microorganisms collected on AAO filters was >= 100% of that extracted from
      pellets of cells and viruses and 94% +/- 9% of that obtained by direct extraction
      of a liquid bacterial culture. The latter is a minimum estimate of the relative
      recovery of microbial DNA, since liquid cultures include dissolved nucleic acids
      that are retained inefficiently by the filter. In conclusion, we demonstrate that
      nucleic acids can be extracted from microorganisms on AAO filters with an
      efficiency similar to that achievable by direct extraction of microbes in
      suspension or in pellets. These filters are therefore a convenient means by which
      to harvest total microbial communities from multiple aqueous samples in parallel
      for subsequent molecular analyses.

PMID- 24747904
TI  - Reconstruction of mreB expression in Staphylococcus aureus via a collection of
      new integrative plasmids.
AB  - Protein localization has been traditionally explored in unicellular organisms,
      whose ease of genetic manipulation facilitates molecular characterization. The
      two rod-shaped bacterial models Escherichia coli and Bacillus subtilis have been
      prominently used for this purpose and have displaced other bacteria whose
      challenges for genetic manipulation have complicated any study of cell biology.
      Among these bacteria is the spherical pathogenic bacterium Staphylococcus aureus.
      In this report, we present a new molecular toolbox that facilitates gene deletion
      in staphylococci in a 1-step recombination process and additional vectors that
      facilitate the insertion of diverse reporter fusions into newly identified
      neutral loci of the S. aureus chromosome. Insertion of the reporters does not add
      any antibiotic resistance genes to the chromosomes of the resultant strains,
      thereby making them amenable for further genetic manipulations. We used this
      toolbox to reconstitute the expression of mreB in S. aureus, a gene that encodes
      an actin-like cytoskeletal protein which is absent in coccal cells and is
      presumably lost during the course of speciation. We observed that in S. aureus,
      MreB is organized in discrete structures in association with the membrane,
      leading to an unusual redistribution of the cell wall material. The production of
      MreB also caused cell enlargement, but it did not revert staphylococcal shape. We
      present interactions of MreB with key staphylococcal cell wall-related proteins.
      This work facilitates the use S. aureus as a model system in exploring diverse
      aspects of cellular microbiology. 

PMID- 24747905
TI  - Insights into the microbial degradation of rubber and gutta-percha by analysis of
      the complete genome of Nocardia nova SH22a.
AB  - The complete genome sequence of Nocardia nova SH22a was determined in light of
      the remarkable ability of rubber and gutta-percha (GP) degradation of this
      strain. The genome consists of a circular chromosome of 8,348,532 bp with a G+C
      content of 67.77% and 7,583 predicted protein-encoding genes. Functions were
      assigned to 72.45% of the coding sequences. Among them, a large number of genes
      probably involved in the metabolism of xenobiotics and hardly degradable
      compounds, as well as genes that participate in the synthesis of polyketide-
      and/or nonribosomal peptide-type secondary metabolites, were detected. Based on
      in silico analyses and experimental studies, such as transposon mutagenesis and
      directed gene deletion studies, the pathways of rubber and GP degradation were
      proposed and the relationship between both pathways was unraveled. The genes
      involved include, inter alia, genes participating in cell envelope synthesis
      (long-chain-fatty-acid-AMP ligase and arabinofuranosyltransferase), beta
      oxidation (alpha-methylacyl-coenzyme A [alpha-methylacyl-CoA] racemase),
      propionate catabolism (acyl-CoA carboxylase), gluconeogenesis
      (phosphoenolpyruvate carboxykinase), and transmembrane substrate uptake (Mce
      [mammalian cell entry] transporter). This study not only improves our insights
      into the mechanism of microbial degradation of rubber and GP but also expands our
      knowledge of the genus Nocardia regarding metabolic diversity. 

PMID- 24747906
TI  - Diversity and transport of microorganisms in intertidal sands of the California
      coast.
AB  - Forced by tides and waves, large volumes of seawater are flushed through the
      beach daily. Organic material and nutrients in seawater are remineralized and
      cycled as they pass through the beach. Microorganisms are responsible for most of
      the biogeochemical cycling in the beach; however, few studies have characterized
      their diversity in intertidal sands, and little work has characterized the extent
      to which microbes are transported between different compartments of the beach.
      The present study uses next-generation massively parallel sequencing to
      characterize the microbial community present at 49 beaches along the coast of
      California. In addition, we characterize the transport of microorganisms within
      intertidal sands using laboratory column experiments. We identified extensive
      diversity in the beach sands. Nearly 1,000 unique taxa were identified in sands
      from 10 or more unique beaches, suggesting the existence of a group of
      "cosmopolitan" sand microorganisms. A biogeographical analysis identified a taxon
      distance relationship among the beaches. In addition, sands with similar grain
      size, organic carbon content, exposed to a similar wave climate, and having the
      same degree of anthropogenic influence tended to have similar microbial
      communities. Column experiments identified microbes readily mobilized by seawater
      infiltrating through unsaturated intertidal sands. The ease with which microbes
      were mobilized suggests that intertidal sands may represent a reservoir of
      bacteria that seed the beach aquifer where they may partake in biogeochemical
      cycling. 

PMID- 24747907
TI  - Posttranscriptional regulation of 2,4-diacetylphloroglucinol production by GidA
      and TrmE in Pseudomonas fluorescens 2P24.
AB  - Pseudomonas fluorescens 2P24 is a soilborne bacterium that synthesizes and
      excretes multiple antimicrobial metabolites. The polyketide compound 2,4
      diacetylphloroglucinol (2,4-DAPG), synthesized by the phlACBD locus, is its major
      biocontrol determinant. This study investigated two mutants defective in
      antagonistic activity against Rhizoctonia solani. Deletion of the gidA (PM701) or
      trmE (PM702) gene from strain 2P24 completely inhibited the production of 2,4
      DAPG and its precursors, monoacetylphloroglucinol (MAPG) and phloroglucinol (PG).
      The transcription of the phlA gene was not affected, but the translation of the
      phlA and phlD genes was reduced significantly. Two components of the Gac/Rsm
      pathway, RsmA and RsmE, were found to be regulated by gidA and trmE, whereas the
      other components, RsmX, RsmY, and RsmZ, were not. The regulation of 2,4-DAPG
      production by gidA and trmE, however, was independent of the Gac/Rsm pathway.
      Both the gidA and trmE mutants were unable to produce PG but could convert PG to
      MAPG and MAPG to 2,4-DAPG. Overexpression of PhlD in the gidA and trmE mutants
      could restore the production of PG and 2,4-DAPG. Taken together, these findings
      suggest that GidA and TrmE are positive regulatory elements that influence the
      biosynthesis of 2,4-DAPG posttranscriptionally. 

PMID- 24747908
TI  - Distributions of Salmonella subtypes differ between two U.S. produce-growing
      regions.
AB  - Salmonella accounts for approximately 50% of produce-associated outbreaks in the
      United States, several of which have been traced back to contamination in the
      produce production environment. To quantify Salmonella diversity and aid in
      identification of Salmonella contamination sources, we characterized Salmonella
      isolates from two geographically diverse produce-growing regions in the United
      States. Initially, we characterized the Salmonella serotype and subtype diversity
      associated with 1,677 samples collected from 33 produce farms in New York State
      (NYS). Among these 1,677 samples, 74 were Salmonella positive, yielding 80 unique
      isolates (from 147 total isolates), which represented 14 serovars and 23
      different pulsed-field gel electrophoresis (PFGE) types. To explore regional
      Salmonella diversity associated with production environments, we collected a
      smaller set of samples (n = 65) from South Florida (SFL) production environments
      and compared the Salmonella diversity associated with these samples with the
      diversity found among NYS production environments. Among these 65 samples, 23
      were Salmonella positive, yielding 32 unique isolates (from 81 total isolates),
      which represented 11 serovars and 17 different PFGE types. The most common
      serovars isolated in NYS were Salmonella enterica serovars Newport, Cerro, and
      Thompson, while common serovars isolated in SFL were Salmonella serovars Saphra
      and Newport and S. enterica subsp. diarizonae serovar 50:r:z. High PFGE type
      diversity (Simpson's diversity index, 0.90 +/- 0.02) was observed among
      Salmonella isolates across both regions; only three PFGE types were shared
      between the two regions. The probability of three or fewer shared PFGE types was
      <0.000001; therefore, Salmonella isolates were considerably different between the
      two sampled regions. These findings suggest the potential for PFGE-based source
      tracking of Salmonella in production environments. 

PMID- 24747909
TI  - HrcT is a key component of the type III secretion system in Xanthomonas spp. and
      also regulates the expression of the key hrp transcriptional activator HrpX.
AB  - The type III secretion system (T3SS), encoded by hrp (hypersensitive response and
      pathogenicity) genes in Gram-negative phytopathogenic bacteria, delivers
      repertoires of T3SS effectors (T3SEs) into plant cells to trigger the
      hypersensitive response (HR) in nonhost or resistant-host plants and promote
      pathogenicity in susceptible plants. The expression of hrp genes in Xanthomonas
      is regulated by two key regulatory proteins, HrpG and HrpX. However, the
      interactions between hrp gene products in directing T3SE secretion are largely
      unknown. Here we demonstrated that HrcT of X. oryzae pv. oryzicola functions as a
      T3SS component and positively regulates the expression of hrpX. Transcription of
      hrcT occurs via two distinct promoters; one (T1) is with the hrpB operon and the
      second (T3) within hrpB7 Via either promoter T1 or T3, the defect in Hrp
      phenotype by hrcT deletion was corrected in the presence of hrcT only from
      Xanthomonas species but not from other phytopathogenic bacteria. An N-terminally
      truncated HrcT was able to bind the hrpX promoter and activate the expression of
      hrpX, supporting that HrcT is a positive regulator of hrpX. A revised model
      showing the regulatory interactions between HrcT, HrpX, and HrpG is proposed. 

PMID- 24747910
TI  - Structure-based mutational studies of substrate inhibition of betaine aldehyde
      dehydrogenase BetB from Staphylococcus aureus.
AB  - Inhibition of enzyme activity by high concentrations of substrate and/or cofactor
      is a general phenomenon demonstrated in many enzymes, including aldehyde
      dehydrogenases. Here we show that the uncharacterized protein BetB (SA2613) from
      Staphylococcus aureus is a highly specific betaine aldehyde dehydrogenase, which
      exhibits substrate inhibition at concentrations of betaine aldehyde as low as
      0.15 mM. In contrast, the aldehyde dehydrogenase YdcW from Escherichia coli,
      which is also active against betaine aldehyde, shows no inhibition by this
      substrate. Using the crystal structures of BetB and YdcW, we performed a
      structure-based mutational analysis of BetB and introduced the YdcW residues into
      the BetB active site. From a total of 32 mutations, those in five residues
      located in the substrate binding pocket (Val288, Ser290, His448, Tyr450, and
      Trp456) greatly reduced the substrate inhibition of BetB, whereas the double
      mutant protein H448F/Y450L demonstrated a complete loss of substrate inhibition.
      Substrate inhibition was also reduced by mutations of the semiconserved Gly234
      (to Ser, Thr, or Ala) located in the BetB NAD(+) binding site, suggesting some
      cooperativity between the cofactor and substrate binding sites. Substrate docking
      analysis of the BetB and YdcW active sites revealed that the wild-type BetB can
      bind betaine aldehyde in both productive and nonproductive conformations, whereas
      only the productive binding mode can be modeled in the active sites of YdcW and
      the BetB mutant proteins with reduced substrate inhibition. Thus, our results
      suggest that the molecular mechanism of substrate inhibition of BetB is
      associated with the nonproductive binding of betaine aldehyde. 

PMID- 24747911
TI  - Inhibiting Tankyrases sensitizes KRAS-mutant cancer cells to MEK inhibitors via
      FGFR2 feedback signaling.
AB  - Tankyrases (TNKS) play roles in Wnt signaling, telomere homeostasis, and mitosis,
      offering attractive targets for anticancer treatment. Using unbiased combination
      screening in a large panel of cancer cell lines, we have identified a strong
      synergy between TNKS and MEK inhibitors (MEKi) in KRAS-mutant cancer cells. Our
      study uncovers a novel function of TNKS in the relief of a feedback loop induced
      by MEK inhibition on FGFR2 signaling pathway. Moreover, dual inhibition of TNKS
      and MEK leads to more robust apoptosis and antitumor activity both in vitro and
      in vivo than effects observed by previously reported MEKi combinations.
      Altogether, our results show how a novel combination of TNKS and MEK inhibitors
      can be highly effective in targeting KRAS-mutant cancers by suppressing a newly
      discovered resistance mechanism.

PMID- 24747912
TI  - Enhancement of the T-cell armamentarium as a cell-based therapy for prostate
      cancer.
AB  - Prostate cancer is frequently characterized by a large inflammatory infiltrate
      that includes T cells. Although T cells traffic to cancer lesions in large
      numbers, they are unable to generate a therapeutic response because of the
      immunosuppressive microenvironment. Therefore, arming T cells with a cytotoxic
      agent that is capable of killing cancer cells independent of these
      immunosuppressive signals is a rational approach to enhance their potency.
      Essentially, the T cells would serve as a cell-based vector, or "Trojan Horse,"
      to selectively deliver a protoxin to disseminated prostate cancer lesions. The
      selective delivery of a protoxin using T cells represents an ideal method to
      maximize their therapeutic potency through a "field effect." Because systemically
      infused T cells are expected to traffic to sites of inflammation other than
      cancer, an additional level of specificity may be needed to prevent toxicity to
      nontarget tissues. Toward this goal, genetic engineering can be used to make
      protoxin expression dependent upon T-cell recognition of the prostate-specific
      membrane antigen by a chimeric antigen receptor. Furthermore, selective
      activation of the protoxin using a tissue- or tumor-specific protease, such as
      PSA, can promote further specificity. Thus, T-cell potency can be enhanced by
      targeted protoxin secretion and greater specificity achieved using combinatorial
      antigen recognition and protoxin activation.

PMID- 24747913
TI  - Alteration of light-dependent gene regulation by the absence of the RCO-1/RCM-1
      repressor complex in the fungus Neurospora crassa.
AB  - The activation of transcription by light in the fungus Neurospora crassa requires
      the White Collar Complex (WCC), a photoreceptor and transcription factor complex.
      After light reception two WCCs interact and bind the promoters of light-regulated
      genes to activate transcription. This process is regulated by VVD, a small
      photoreceptor that disrupts the interaction between WCCs and leads to a reduction
      in transcription after long exposures to light. The N. crassa RCO-1/RCM-1
      repressor complex is the homolog of the Tup1-Ssn6 repressor complex in yeast, and
      its absence modifies photoadaptation. We show that the absence of the RCO-1/RCM-1
      repressor complex leads to several alterations in transcription that are gene
      specific: an increase in the accumulation of mRNAs in the dark, a repression of
      transcription, and a derepression of transcription after long exposures to light.
      The absence of the RCO-1/RCM-1 repressor complex leads to lower VVD levels that
      are available for the regulation of the activity of the WCC. The reduction in the
      amount of VVD results in increased WCC binding to the promoters of light
      regulated genes in the dark and after long exposures to light, leading to the
      modification of photoadaptation that has been observed in rco-1 and rcm-1
      mutants. Our results show that the photoadaptation phenotype of mutants in the
      RCO-1/RCM-1 repressor complex is, at least in part, an indirect consequence of
      the reduction of vvd transcription, and the resulting modification in the
      regulation of transcription by the WCC. 

PMID- 24747914
TI  - Optimization of multimodal imaging of mesenchymal stem cells using the human
      sodium iodide symporter for PET and Cerenkov luminescence imaging.
AB  - PURPOSE: The use of stably integrated reporter gene imaging provides a manner to
      monitor the in vivo fate of engrafted cells over time in a non-invasive manner.
      Here, we optimized multimodal imaging (small-animal PET, Cerenkov luminescence
      imaging (CLI) and bioluminescence imaging (BLI)) of mesenchymal stem cells
      (MSCs), by means of the human sodium iodide symporter (hNIS) and firefly
      luciferase (Fluc) as reporters. METHODS: First, two multicistronic lentiviral
      vectors (LV) were generated for multimodal imaging: BLI, 124I PET/SPECT and CLI.
      Expression of the imaging reporter genes was validated in vitro using 99mTcO4-
      radioligand uptake experiments and BLI. Uptake kinetics, specificity and tracer
      elution were determined as well as the effect of the transduction process on the
      cell's differentiation capacity. MSCs expressing the LV were injected
      intravenously or subcutaneously and imaged using small-animal PET, CLI and BLI.
      RESULTS: The expression of both imaging reporter genes was functional and
      specific. An elution of 99mTcO4- from the cells was observed, with 31% retention
      after 3 h. After labeling cells with 124I in vitro, a significantly higher CLI
      signal was noted in hNIS expressing murine MSCs. Furthermore, it was possible to
      visualize cells injected intravenously using BLI or subcutaneously in mice, using
      124I small-animal PET, CLI and BLI. CONCLUSIONS: This study identifies hNIS as a
      suitable reporter gene for molecular imaging with PET and CLI, as confirmed with
      BLI through the expression of Fluc. It supports the potential for a wider
      application of hNIS reporter gene imaging and future clinical applications.

PMID- 24747915
TI  - Evidence for polyphyly of the genus Scrupocellaria (Bryozoa: Candidae) based on a
      phylogenetic analysis of morphological characters.
AB  - The bryozoan genus Scrupocellaria comprises about 80 species in the family
      Candidae. We propose a hypothesis for the phylogenetic relationships among
      species assigned to Scrupocellaria to serve as framework for a phylogenetic
      classification using 35 morphological characters. Our results suggest that the
      genus Scrupocellaria is polyphyletic. Scrupocellaria s. str. is redefined
      according to four morphological features: vibracular chamber with a curved setal
      groove, ooecium with a single ectooecial fenestra, two axillary vibracula, and a
      membranous operculum with a distinct distal rim. Thus, the genus includes only 11
      species: Scrupocellaria aegeensis, Scrupocellaria delilii, Scrupocellaria
      harmeri, Scrupocellaria incurvata, Scrupocellaria inermis, Scrupocellaria
      intermedia, Scrupocellaria jullieni, Scrupocellaria minuta, Scrupocellaria
      puelcha, Scrupocellaria scrupea, and Scrupocellaria scruposa. The monophyly of
      Cradoscrupocellaria is supported and five new genera are erected: Aquiloniella n.
      gen., Aspiscellaria n. gen., Paralicornia n. gen., Pomocellaria n. gen. and
      Scrupocaberea n. gen. Two other new genera, Bathycellaria n. gen. and
      Sinocellaria n. gen., are erected to accommodate two poorly known species,
      Scrupocellaria profundis Osburn and Scrupocellaria uniseriata Liu, respectively.
      Scrupocellaria congesta is tentatively assigned to Tricellaria. Fifteen species
      are reassigned to Licornia: Licornia cookie n. comb., Licornia micheli n. comb.,
      Licornia milneri n. comb., Licornia curvata n. comb., Licornia diegensis n.
      comb., Licornia drachi n. comb., Licornia mexicana n. comb., Licornia pugnax n.
      comb., Licornia raigadensis n. comb., Licornia regularis n. comb., Licornia
      resseri n. comb., Licornia securifera n. comb., Licornia spinigera n. comb.,
      Licornia tridentata n. comb., and Licornia wasinensis n. comb. Notoplites
      americanus n. name is proposed as a replacement name for Scrupocellaria clausa
      Canu & Bassler. Three fossil species are reassigned to Canda: Canda rathbuni n.
      comb., Canda triangulata n. comb. and Canda williardi n. comb. A species is
      reassigned to Notoplites, Notoplites elegantissima n. comb. The generic
      assignment of eleven species of Scrupocellaria, including Scrupocellaria
      macandrei, remains uncertain. 

PMID- 24747916
TI  - Imbalance of Wnt/Dkk negative feedback promotes persistent activation of
      pancreatic stellate cells in chronic pancreatitis.
AB  - The role of persistent activation of pancreatic stellate cells (PSCs) in the
      fibrosis associated with chronic pancreatitis (CP) is increasingly being
      recognized. Recent studies have shown that Wnt signaling is involved in the
      development of fibrosis in multiple organs, however, the role of specific Wnts in
      pancreatic fibrosis remains unknown. We investigated the role of Wnt signaling
      during PSC activation in CP and the effect of beta-catenin inhibition and
      Dickkopf-related protein 1 (Dkk1) restoration on the phenotype of PSCs. CP was
      induced in mice by repetitive caerulein injection and mouse PSCs were isolated
      and activated in vitro. The expression of Wnts, beta-catenin, secreted frizzled
      related proteins (sFRPs) and Dkks was analyzed by quantitative RT-PCR and western
      blotting. The canonical Wnt signaling pathway was examined by immunofluorescence
      and western blot detection of nuclear beta-catenin expression. The effect of
      recombinant mouse Dkk-1 (rmDkk-1) on cell proliferation and apoptosis was
      assessed by flow cytometry, immunofluorescence, immunocytochemistry and Cell
      Counting Kit-8 (CCK-8) analysis. The expression of beta-catenin, collagen1alpha1,
      TGFbetaRII, PDGFRbeta and alpha-SMA in PSCs treated with different concentrations
      of rmDkk-1 or siRNA against beta-catenin was determined by quantitative RT-PCR
      and western blotting. Wnt2 was the only Wnt whose expression was significantly
      upregulated in response to PSC activation, and Wnt2 and beta-catenin protein
      levels were significantly increased in the pancreas of CP mice, whereas Dkk-1
      expression was evidently decreased. Nuclear beta-catenin levels were markedly
      increased in activated PSCs, and rmDkk-1 suppressed the nuclear translocation of
      beta-catenin and the proliferation and extracellular matrix production of PSCs
      through the downregulation of PDGFRbeta and TGFbetaRII. Upregulation of Dkk-1
      expression increased apoptosis in cultured PSCs. These results indicate that Wnt
      signaling may mediate the profibrotic effect of PSC activation, and Wnt2/Dkk-1
      could be potential therapeutic targets for CP. 

PMID- 24747917
TI  - EEG mu rhythm in typical and atypical development.
AB  - Electroencephalography (EEG) is an effective, efficient, and noninvasive method
      of assessing and recording brain activity. Given the excellent temporal
      resolution, EEG can be used to examine the neural response related to specific
      behaviors, states, or external stimuli. An example of this utility is the
      assessment of the mirror neuron system (MNS) in humans through the examination of
      the EEG mu rhythm. The EEG mu rhythm, oscillatory activity in the 8-12 Hz
      frequency range recorded from centrally located electrodes, is suppressed when an
      individual executes, or simply observes, goal directed actions. As such, it has
      been proposed to reflect activity of the MNS. It has been theorized that
      dysfunction in the mirror neuron system (MNS) plays a contributing role in the
      social deficits of autism spectrum disorder (ASD). The MNS can then be
      noninvasively examined in clinical populations by using EEG mu rhythm attenuation
      as an index for its activity. The described protocol provides an avenue to
      examine social cognitive functions theoretically linked to the MNS in individuals
      with typical and atypical development, such as ASD.  

PMID- 24747918
TI  - Immunotherapeutic interventions in chronic hepatitis B virus infection: a review.
AB  - Chronic hepatitis B virus (HBV) infection is a public health challenge worldwide.
      Antiviral agents (nucleos(t)ide analogues, NAs) and immune-based therapies (IFN
      alpha or Pegylated-IFN-alpha) are two therapeutic approaches available currently
      against chronic hepatitis B (CHB). However, these approaches are associated with
      the development of acquired drug resistance or poor response rates and are
      accompanied by numerous side effects. Furthermore, due to defective innate and
      adaptive immune responses, HBV cannot be effectively controlled or completely
      eliminated, which may ultimately result in liver decompensation and hepatocelluar
      carcinoma. The imperative for development of new approaches targeting CHB cannot
      be overstated. Various immunotherapeutic interventions have been tried as
      adjuvants to inhibit HBV replication. In this paper, we will review
      immunotherapeutic interventions in the treatment of CHB. 

PMID- 24747919
TI  - Conclusiveness of toxicity data and double standards.

PMID- 24747920
TI  - A tale of two cities? The heterogeneous impact of Medicaid managed care.
AB  - Evaluating Accountable Care Organizations is difficult because there is a great
      deal of heterogeneity in terms of their reimbursement incentives and other
      programmatic features. We examine how variation in reimbursement incentives and
      administration among two Medicaid managed care plans impacts utilization and
      spending. We use a quasi-experimental approach exploiting the timing and county
      specific implementation of Medicaid managed care mandates in two contiguous
      regions of Kentucky. We find large differences in the relative success of each
      plan in reducing utilization and spending that are likely driven by important
      differences in plan design. The plan that capitated primary care physicians and
      contracted out many administrative responsibilities to an experienced managed
      care organization achieved significant reductions in outpatient and professional
      utilization. The plan that opted for a fee-for-service reimbursement scheme with
      a group withhold and handled administration internally saw a much more modest
      reduction in outpatient utilization and an increase in professional utilization. 

PMID- 24747921
TI  - Extending the Failure-to-Engage theory of task switch costs.
AB  - Failure-to-Engage (FTE, De Jong, 2000) theory explains slowed response time after
      switching tasks as in part due to participants sometimes failing to prepare.
      Brown et al. (2006) rejected FTE because, in an alternating-runs paradigm, they
      did not observe fixed crossing point between response-time distributions that it
      predicts. We replicated these findings in a cued-task paradigm that allowed us to
      separately examine the effects of response-to-target interval and cue-to-target
      interval. These results guided an extension of FTE that was tested in a further
      experiment and shown to be able to accommodate the effects of the interval
      manipulations as well as both task and cue switching. We then apply a new
      modeling approach to obtain direct estimates of the probability of preparation
      and conclude that De Jong's insights about preparation failure provide a
      tractable framework that can explain aspects of all of the four major task
      switching phenomena identified by Monsell (2003). 

PMID- 24747922
TI  - Methods for targeted mutagenesis in zebrafish using TALENs.
AB  - The transcription activator-like effector (TALE) nucleases, or TALENs, are
      customizable restriction enzymes that may be used to induce mutations at nearly
      any investigator-specified DNA sequence in zebrafish. The DNA-binding
      specificities of TALENs are determined by a protein array comprised of four types
      of TALE repeats, where each repeat recognizes a different DNA base. Here, we
      describe methods for constructing TALEN vectors that have been shown to achieve
      high success rates and mutation efficiencies in zebrafish. In addition, we
      discuss simple techniques and protocols that can be used to detect TALEN-induced
      mutations at almost any genomic locus. These methods should enable zebrafish
      researchers to quickly generate targeted mutations at their genes-of-interest. 

PMID- 24747923
TI  - Developments in in situ hybridisation.
AB  - In situ hybridisation (ISH) is an established family of closely related methods
      for the detection and visualisation of specific nucleic acid sequences (DNA, RNA)
      in tissue sections, cytological preparations and whole organisms. The technique
      has a history of refinements and applications going back over several decades and
      is routinely employed in laboratories where visualisation of gene expression
      directly within the tissue of interest is necessary. This article will focus on
      ISH methods for the demonstration of messenger RNA (mRNA) and micro RNA (miRNA)
      in formalin-fixed paraffin-embedded (FFPE) tissues with emphasis on non
      radioactive signal detection strategies currently available. 

PMID- 24747924
TI  - Surrogates of peripheral microcirculation to predict weaning failure, yet another
      piece of the puzzle.

PMID- 24747925
TI  - From intraoperative to perioperative pulse oximetry - can we add value for our
      patients?

PMID- 24747926
TI  - Toxicity of sediments from a mangrove forest patch in an urban area in Pernambuco
      (Brazil).
AB  - Industrial and urban residues are discharged every day to the rivers and may
      arrive at the mangrove forest and prejudice the quality of the environment and
      the organisms present there. The mangrove forest patch studied is encircled by an
      urban area of the city of Recife (Brazil) that has approximate 1.5 million
      inhabitants and is one of the most industrialized centers in Northeast Brazil.
      The aim of this study was to assess the quality of the sediments of this mangrove
      patch in terms of metal contamination and ecotoxicology. Samples of surface
      sediment were collected in six stations for toxicological tests and trace metal
      determination (Cr, Zn, Mn, Fe, Cu, Pb, Co and Ni), in July and August, 2006
      (rainy season); and in January and February 2007 (dry season). Toxicity tests
      with solid-phase sediments were carried out with the copepod Tisbe biminiensis in
      order to observe lethal and sub-lethal endpoints and correlate them with chemical
      data. In June, there were no observed lethal effect, but two stations presented
      sub-lethal effects. In January, lethal effect occurred in three stations and sub
      lethal in one station. The levels for Zn and Cr were at higher levels than
      international proposed guidelines (NOAA). There was a negative significant
      correlation between the copepods' fecundity, and Zn and Cr concentrations.
      Therefore, the studied sediments can be considered to have potential toxic to
      benthos due to the high content of Zn and Cr. 

PMID- 24747927
TI  - Uptake and acute toxicity of cerium in the lichen Xanthoria parietina.
AB  - Environmental cerium (Ce) levels are likely to increase in the near future and
      monitoring of its biological effects will therefore be necessary. The aim of this
      study was to test if treatment of the lichen Xanthoria parietina with Ce
      containing solutions (0.1mM, 1mM, 10mM and 100mM) causes Ce bioaccumulation (both
      extra- and intra-cellularly) as well as physiological (sample viability, membrane
      lipids peroxidation, photosynthetic performance, water-soluble proteins content)
      and ultrastructural alterations. The results showed that treatment with Ce
      solutions induces Ce bioaccumulation, both extra-cellularly and intra-cellularly,
      which in turn causes an acute toxicity, evident as decreased sample viability,
      marked decrease in the photosynthetic performance and important changes in the
      ultrastructure. 

PMID- 24747928
TI  - Solid state synthesis and spectral investigations of nanostructure SnS2.
AB  - Nanometer sized SnS2 particles were synthesised by solid state reaction between
      tin chloride and thiourea in air at 150-350 degrees C. The structural,
      morphological and optical properties were characterized by using X-ray
      diffraction (XRD), FT-IR, FT-Raman, scanning electron microscopy (SEM), energy
      dispersive spectroscopy (EDS), field emission scanning electron microscopy (FE
      SEM), photoluminescence (PL) and UV-Vis spectra. The X-ray diffraction (XRD)
      pattern of the product was indexed to the hexagonal phase of SnS2. Crystallite
      size, microstrain and dislocation density were evaluated from the XRD data. EDS
      analysis indicated that the elemental ratio was similar to tin disulphide (SnS2).
      The blue shift in the absorption edge was observed from the UV-Vis spectrum. The
      photoluminescence spectra showed two emission peaks corresponding to blue and red
      emission. 

PMID- 24747929
TI  - Ab initio/DFT calculations of butyl ammonium salt of O,O'-dibornyl
      dithiophosphate.
AB  - O,O'-dibornyl dithiophosphete has been synthesized by the reaction of P2S5 and
      borneol in toluene. Fourier Transform Infrared spectra (FT-IR) of the title
      compound are measured. The molecular geometry, vibrational frequencies, infrared
      intensities and NMR spectrum of the title compound in the ground state have been
      calculated by using the density functional theory (DFT) and ab initio Hartree
      Fock (HF) methods with the basis set of 6-31G(d). The computed bond lengths and
      bond angles show the good agreement with the experimental data. Moreover, the
      vibrational frequencies are calculated and the scaled values have been compared
      with experimental FT-IR spectra. Assignments of the vibrational modes are made on
      the basis of total energy distribution (TED) calculated with scaled quantum
      mechanical (SQM) method. The observed and calculated FT-IR and NMR spectra are in
      good agreement with each other. 

PMID- 24747930
TI  - Synthesis, characterization, crystal structure and theoretical study of a
      compound with benzodiazole ring: antimicrobial activity and DNA binding.
AB  - 2-(Thiophen-2-yl)-1-((thiophen-2-yl)methyl)-1H-1,3-benzodiazole (HL) is
      synthesized and characterized by elemental analysis, UV-Vis, FT-IR, (1)H, (13)C
      NMR, mass spectra, scanning electron microscope (SEM) and single crystal X-ray
      diffraction. The crystal structure is stabilized by intermolecular CH?N and CH?pi
      interactions. The molecular structure is also optimized at the B3LYP/6-31G level
      using density functional theory (DFT). The structural parameters from the theory
      are nearer to those of crystal, the calculated total energy of coordination is 
      1522.814a.u. The energy of HOMO-LUMO and the energy gap are -0.20718, -0.04314,
      0.16404a.u, respectively. All data obtained from the spectral studies support the
      structural properties of the compound HL. The benzimidazole ring is essentially
      planar. The in vitro biological screening effects of the synthesized compound is
      tested against four bacterial and four fungal strains by well diffusion method.
      Antioxidant property and DNA binding behaviour of the compound has been
      investigated using spectrophotometric method. 

PMID- 24747931
TI  - Spectroscopic (FT-IR, FT-Raman) investigations and quantum chemical calculations
      of 1,7,8,9-tetrachloro-10,10-dimethoxy-4-{3-[4-(3-methoxyphenyl)piperazin-1
      yl]propyl}-4-azatricyclo[5.2.1.0(2,6)]dec-8-ene-3,5-dione.
AB  - The optimized molecular structure, vibrational frequencies, corresponding
      vibrational assignments of 1,7,8,9-tetrachloro-10,10-dimethoxy-4-{3-[4-(3
      methoxyphenyl) piperazin-1-yl]propyl}-4-azatricyclo[5.2.1.0(2,6)]dec-8-ene-3,5
      dione have been investigated experimentally and theoretically using Gaussian09
      software package. The stability of the molecule arising from hyper-conjugative
      interaction and charge delocalization has been analyzed using NBO analysis. Gauge
      including atomic orbital (1)H NMR chemical shifts calculations were carried out
      and compared with experimental data. The HOMO and LUMO analysis is used to
      determine the charge transfer within the molecule. Molecular Electrostatic
      Potential was performed by the DFT method and the infrared and Raman intensities
      have also been reported. First hyperpolarizability is calculated in order to find
      its role in non-liner optics. The calculated geometrical parameters (SDD) are in
      agreement with that of similar derivatives. Mulliken's net charges have been
      calculated and compared with the atomic natural charges. 

PMID- 24747933
TI  - Isolation of estrogen receptor subtypes and vitellogenin genes: expression in
      female Chalcalburnus tarichi.
AB  - Reproductively arrested gonadal development has been previously described in the
      teleost pearl mullet (Chalcalburnus tarichi, Cyprinidae) from Van Edremit Gulf of
      Lake Van, Turkey. Oocyte development in some females was arrested at the
      previtellogenic stage, while gonadosomatic index (GSI) and plasma 17beta
      estradiol (E2) level were low. A subset of the females was found to have normal
      ovaries and relatively higher plasma E2 and GSI. These two groups were termed
      reproductively arrested (RA) and reproductively non-arrested (RN) females. In
      this study, we cloned estrogen receptor (ER) isoforms (ERalpha, ERbeta1 and
      ERbeta2) and vitellogenin (Vtg), and their mRNA levels were measured in RA and RN
      fish tissues. C. tarichi ERs fell in the same clade with other fish ERs and
      ERalpha and ERbeta1 had 97% and 98% identity with the roach (Rutilus rutilus)
      ERs, respectively. Both Vtg and ER isoforms' mRNA abundance were higher in the
      liver than in the ovary and hypothalamus (liver>ovary>hypothalamus). The level of
      ERalpha mRNA was significantly lower in the liver, ovary and brain of RA fish
      than in the RN fish tissues. ERbeta1 mRNA levels were not different in the liver
      and ovary from RA and RN fish while ERbeta2 expression significantly increased in
      the liver and ovary from RA fish. All ER subtype expression was found to be lower
      in the brain from RA fish than RN fish. The level of Vtg mRNA was significantly
      lower in the liver and ovary from RA fish than RN fish tissue. These results
      suggest that ER subtypes are differentially regulated by E2, and their functions
      are also different in vitellogenesis. Analysis of organic contaminants in
      sediments revealed that C. tarichi living in Van Edremit Gulf of Lake Van are
      exposed to the contaminants bis(2-ethylhexyl) phthalate and 4,4(') DDT. We
      suggest that the RA fish represent a segment of the population that is more
      sensitive to exposure to endocrine disrupting compounds. 

PMID- 24747934
TI  - Permeable Adsorptive Barrier (PAB) for the remediation of groundwater
      simultaneously contaminated by some chlorinated organic compounds.
AB  - In this paper, a Permeable Reactive Barrier (PRB) made with activated carbon,
      namely a Permeable Adsorptive Barrier (PAB), is put forward as an effective
      technique for the remediation of aquifers simultaneously contaminated by some
      chlorinated organic compounds. A design procedure, based on a computer code and
      including different routines, is presented as a tool to accurately describe mass
      transport within the aquifer and adsorption/desorption phenomena occurring inside
      the barrier. The remediation of a contaminated aquifer near a solid waste
      landfill in the district of Napoli (Italy), where Tetrachloroethylene (PCE) and
      Trichloroethylene (TCE) are simultaneously present, is considered as a case
      study. A complete hydrological and geotechnical site characterization, as well as
      a number of dedicated adsorption laboratory tests for the determination of
      activated carbon PCE/TCE adsorption capacity in binary systems, are carried out
      to support the barrier design. By means of a series of numerical simulations it
      is possible to determine the optimal barrier location, orientation and
      dimensions. PABs appear to be an effective remediation tool for the in-situ
      treatment of an aquifer contaminated by PCE and TCE simultaneously, as the
      concentration of both compounds flowing out of the barrier is everywhere lower
      than the regulatory limits on groundwater quality. 

PMID- 24747932
TI  - Design of the Violence and Stress Assessment (ViStA) study: a randomized
      controlled trial of care management for PTSD among predominantly Latino patients
      in safety net health centers.
AB  - Posttraumatic stress disorder (PTSD) is a common problem in primary care.
      Although effective treatments are available, little is known about whether such
      treatments are effective within the context of Federally Qualified Health Centers
      (FQHCs) that serve as national "safety nets" for providing primary care for low
      income and underinsured patients. The Violence and Stress Assessment (ViStA)
      study is the first randomized controlled trial (RCT) to test the impact of a care
      management intervention for treating PTSD in FQHCs. To develop a PTSD management
      intervention appropriate for lower resource FQHCs and the predominantly Latino
      patients they serve, formative work was conducted through a collaborative effort
      between researchers and an FQHC practice-based research network. This article
      describes how FQHC stakeholders were convened to review, assess, and prioritize
      evidence-based strategies for addressing patient, clinician, and system-level
      barriers to care. This multi-component care management intervention incorporates
      diagnosis with feedback, patient education and activation; navigation and linkage
      to community resources; clinician education and medication guidance; and
      structured cross-disciplinary communication and continuity of care, all
      facilitated by care managers with FQHC experience. We also describe the
      evaluation design of this five-year RCT and the characteristics of the 404
      English or Spanish speaking patients enrolled in the study and randomized to
      either the intervention or to usual care. Patients are assessed at baseline, six
      months, and 12 months to examine intervention effectiveness on PTSD, other mental
      health symptoms, health-related quality-of-life, health care service use; and
      perceived barriers to care and satisfaction with care.

PMID- 24747936
TI  - Evaluation of metal partitioning and mobility in a sulfidic mine tailing pile
      under oxic and anoxic conditions.
AB  - Mining-influenced water emanating from mine tailings and potentially
      contaminating surface water and groundwater is one of the most important
      environmental issues linked to the mining industry. In this study, two subsets of
      Callahan Mine tailings (mainly comprised of silicates, sulfides, and carbonates)
      were collected using sealed containers, which allowed keeping the samples under
      anoxic conditions during transportation and storage. Among the potential
      contaminants, in spite of high concentrations of Cu, Mn, Pb, and Zn present in
      the solid mine tailings, only small amounts of Mn and Zn were found in the
      overlying pore water. The samples were subjected to leaching tests at different
      reduction-oxidation (redox) conditions to compare metal and S mobilization under
      oxic and anoxic conditions. It was observed that Cd, Cu, Mn, Pb, S, and Zn were
      mobilized at higher rates under oxic conditions, while Fe was mobilized at a
      higher rate under anoxic conditions in comparable constant pH experiments. These
      results suggest that metal mobilization is significantly impacted by redox
      conditions. When anoxic metal mobilization assessment is required, it is
      recommended to always maintain anoxic conditions because oxygen exposure may
      affect metal mobilization. A sequential extraction performed under oxic
      conditions revealed that most of the metals in the samples were associated with
      the sulfidic fraction and that the labile fraction was associated with Mn and
      moderate amounts of Pb and Zn. 

PMID- 24747935
TI  - Assessing agro-environmental performance of dairy farms in northwest Italy based
      on aggregated results from indicators.
AB  - Dairy farms control an important share of the agricultural area of Northern
      Italy. Zero grazing, large maize-cropped areas, high stocking densities, and high
      milk production make them intensive and prone to impact the environment.
      Currently, few published studies have proposed indicator sets able to describe
      the entire dairy farm system and their internal components. This work had four
      aims: i) to propose a list of agro-environmental indicators to assess dairy
      farms; ii) to understand which indicators classify farms best; iii) to evaluate
      the dairy farms based on the proposed indicator list; iv) to link farmer
      decisions to the consequent environmental pressures. Forty agro-environmental
      indicators selected for this study are described. Northern Italy dairy systems
      were analysed considering both farmer decision indicators (farm management) and
      the resulting pressure indicators that demonstrate environmental stress on the
      entire farming system, and its components: cropping system, livestock system, and
      milk production. The correlations among single indicators identified redundant
      indicators. Principal Components Analysis distinguished which indicators provided
      meaningful information about each pressure indicator group. Analysis of the
      communalities and the correlations among indicators identified those that best
      represented farm variability: Farm Gate N Balance, Greenhouse Gas Emission, and
      Net Energy of the farm system; Net Energy and Gross P Balance of the cropping
      system component; Energy Use Efficiency and Purchased Feed N Input of the
      livestock system component; N Eco-Efficiency of the milk production component.
      Farm evaluation, based on the complete list of selected indicators demonstrated
      organic farming resulted in uniformly high values, while farms with low milk
      producing herds resulted in uniformly low values. Yet on other farms, the
      environmental quality varied greatly when different groups of pressure indicators
      were considered, which highlighted the importance of expanding environmental
      analysis to effects within the farm. Statistical analysis demonstrated positive
      correlations between all farmer decision and pressure group indicators.
      Consumption of mineral fertiliser and pesticide negatively influenced the
      cropping system. Furthermore, stocking rate was found to correlate positively
      with the milk production component and negatively with the farm system. This
      study provides baseline references for ex ante policy evaluation, and monitoring
      tools for analysis both in itinere and ex post environment policy implementation.

PMID- 24747937
TI  - Activated carbons obtained from sewage sludge by chemical activation: gas-phase
      environmental applications.
AB  - The objective of this study was to evaluate the adsorption capacity for toluene
      and SO2 of low cost activated carbons prepared from sewage sludge by chemical
      activation at different impregnation ratios. Samples were characterized by
      proximate and ultimate analyses, thermogravimetry, infrared spectroscopy and N2
      adsorption. Because of the low carbon content of the raw material, the
      development of porosity in the activated carbons was mainly of a mesoporous
      nature, with surface areas lower than 300 m(2)/g. The study of gas-phase
      applications for activated carbons from sewage sludge was carried out using both
      an organic and an inorganic compound in order to screen for possible
      applications. Toluene adsorption capacity at saturation was around 280 mg/g,
      which is a good level of performance given the high ash content of the activated
      carbons. However, dynamic experiments at low toluene concentration presented
      diffusion problems resulting from low porosity development. SO2 adsorption
      capacity is associated with average micropore size, which can be controlled by
      the impregnation ratio used to prepare the activated carbons.

PMID- 24747938
TI  - Effect of climate change on soil temperature in Swedish boreal forests.
AB  - Complex non-linear relationships exist between air and soil temperature responses
      to climate change. Despite its influence on hydrological and biogeochemical
      processes, soil temperature has received less attention in climate impact
      studies. Here we present and apply an empirical soil temperature model to four
      forest sites along a climatic gradient of Sweden. Future air and soil temperature
      were projected using an ensemble of regional climate models. Annual average air
      and soil temperatures were projected to increase, but complex dynamics were
      projected on a seasonal scale. Future changes in winter soil temperature were
      strongly dependent on projected snow cover. At the northernmost site, winter soil
      temperatures changed very little due to insulating effects of snow cover but
      southern sites with little or no snow cover showed the largest projected winter
      soil warming. Projected soil warming was greatest in the spring (up to 4 degrees
      C) in the north, suggesting earlier snowmelt, extension of growing season length
      and possible northward shifts in the boreal biome. This showed that the projected
      effects of climate change on soil temperature in snow dominated regions are
      complex and general assumptions of future soil temperature responses to climate
      change based on air temperature alone are inadequate and should be avoided in
      boreal regions. 

PMID- 24747939
TI  - Conformational dynamics of ligand-dependent alternating access in LeuT.
AB  - The leucine transporter (LeuT) from Aquifex aeolicus is a bacterial homolog of
      neurotransmitter/sodium symporters (NSSs) that catalyze reuptake of
      neurotransmitters at the synapse. Crystal structures of wild-type and mutants of
      LeuT have been interpreted as conformational states in the coupled transport
      cycle. However, the mechanistic identities inferred from these structures have
      not been validated, and the ligand-dependent conformational equilibrium of LeuT
      has not been defined. Here, we used distance measurements between spin-label
      pairs to elucidate Na(+)- and leucine-dependent conformational changes on the
      intracellular and extracellular sides of the transporter. The results identify
      structural motifs that underlie the isomerization of LeuT between outward-facing,
      inward-facing and occluded states. The conformational changes reported here
      present a dynamic picture of the alternating-access mechanism of LeuT and NSSs
      that is different from the inferences reached from currently available structural
      models.

PMID- 24747940
TI  - Evidence for a group II intron-like catalytic triplex in the spliceosome.
AB  - To catalyze pre-mRNA splicing, U6 small nuclear RNA positions two metals that
      interact directly with the scissile phosphates. U6 metal ligands correspond
      stereospecifically to metal ligands within the catalytic domain V of a group II
      self-splicing intron. Domain V ligands are organized by base-triple interactions,
      which also juxtapose the 3' splice site with the catalytic metals. However, in
      the spliceosome, the mechanism for organizing catalytic metals and recruiting the
      substrate has remained unclear. Here we show by genetics, cross-linking and
      biochemistry in yeast that analogous triples form in U6 and promote catalytic
      metal binding and both chemical steps of splicing. Because the triples include an
      element that defines the 5' splice site, they also provide a mechanism for
      juxtaposing the pre-mRNA substrate with the catalytic metals. Our data indicate
      that U6 adopts a group II intron-like tertiary conformation to catalyze splicing.

PMID- 24747942
TI  - Sample drift correction following 4D confocal time-lapse imaging.
AB  - The generation of four-dimensional (4D) confocal datasets; consisting of 3D image
      sequences over time; provides an excellent methodology to capture cellular
      behaviors involved in developmental processes.  The ability to track and follow
      cell movements is limited by sample movements that occur due to drift of the
      sample or, in some cases, growth during image acquisition. Tracking cells in
      datasets affected by drift and/or growth will incorporate these movements into
      any analysis of cell position. This may result in the apparent movement of static
      structures within the sample. Therefore prior to cell tracking, any sample drift
      should be corrected. Using the open source Fiji distribution (1)  of ImageJ (2,3)
      and the incorporated LOCI tools (4), we developed the Correct 3D drift plug-in to
      remove erroneous sample movement in confocal datasets. This protocol effectively
      compensates for sample translation or alterations in focal position by utilizing
      phase correlation to register each time-point of a four-dimensional confocal
      datasets while maintaining the ability to visualize and measure cell movements
      over extended time-lapse experiments. 

PMID- 24747941
TI  - Conformational changes required for H(+)/Cl(-) exchange mediated by a CLC
      transporter.
AB  - CLC-type exchangers mediate transmembrane Cl(-) transport. Mutations altering
      their gating properties cause numerous genetic disorders. However, their
      transport mechanism remains poorly understood. In conventional models, two gates
      alternatively expose substrates to the intra- or extracellular solutions. A
      glutamate was identified as the only gate in the CLCs, suggesting that CLCs
      function by a nonconventional mechanism. Here we show that transport in CLC-ec1,
      a prokaryotic homolog, is inhibited by cross-links constraining movement of helix
      O far from the transport pathway. Cross-linked CLC-ec1 adopts a wild-type-like
      structure, indicating stabilization of a native conformation. Movements of helix
      O are transduced to the ion pathway via a direct contact between its C terminus
      and a tyrosine that is a constitutive element of the second gate of CLC
      transporters. Therefore, the CLC exchangers have two gates that are coupled
      through conformational rearrangements outside the ion pathway.

PMID- 24747943
TI  - Urotensin II promotes atherosclerosis in cholesterol-fed rabbits.
AB  - Urotensin II (UII) is a vasoactive peptide composed of 11 amino acids that has
      been implicated to contribute to the development of cardiovascular disease. The
      purpose of this study was to investigate whether UII affects the development of
      atherosclerosis in cholesterol-fed rabbits. UII was infused for 16 weeks through
      an osmotic mini-pump into male Japanese White rabbits fed on a high-cholesterol
      diet. Plasma lipids and body weight were measured every 4 weeks. Aortic
      atherosclerotic lesions along with cellular components, collagen fibers, matrix
      metalloproteinase-1 and -9 were examined. Moreover, vulnerability index of
      atherosclerotic plaques was evaluated. UII infusion significantly increased
      atherosclerotic lesions within the entire aorta by 21% over the control (P =
      0.013). Atherosclerotic lesions were increased by 24% in the aortic arch (P =
      0.005), 11% in the thoracic aorta (P = 0.054) and 18% in the abdominal aorta (P =
      0.035). These increases occurred without changes in plasma levels of total
      cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein
      cholesterol, triglycerides or body weight. Immunohistochemical staining revealed
      that macrophages and matrix metalloproteinase-9 were significantly enhanced by
      2.2-fold and 1.6-fold in UII group. In vitro studies demonstrated that UII up
      regulated the expression of vascular cell adhesion protein-1 and intercellular
      adhesion molecule-1 in human umbilical vein endothelial cells, which was
      inhibited by the UII receptor antagonist urantide. In conclusion, our results
      showed that UII promotes the development of atherosclerotic lesions and
      destabilizes atherosclerotic plaques in cholesterol-fed rabbits. 

PMID- 24747944
TI  - Correlated miR-mRNA expression signatures of mouse hematopoietic stem and
      progenitor cell subsets predict "Stemness" and "Myeloid" interaction networks.
AB  - Several individual miRNAs (miRs) have been implicated as potent regulators of
      important processes during normal and malignant hematopoiesis. In addition, many
      miRs have been shown to fine-tune intricate molecular networks, in concert with
      other regulatory elements. In order to study hematopoietic networks as a whole,
      we first created a map of global miR expression during early murine
      hematopoiesis. Next, we determined the copy number per cell for each miR in each
      of the examined stem and progenitor cell types. As data is emerging indicating
      that miRs function robustly mainly when they are expressed above a certain
      threshold (~100 copies per cell), our database provides a resource for
      determining which miRs are expressed at a potentially functional level in each
      cell type. Finally, we combine our miR expression map with matched mRNA
      expression data and external prediction algorithms, using a Bayesian modeling
      approach to create a global landscape of predicted miR-mRNA interactions within
      each of these hematopoietic stem and progenitor cell subsets. This approach
      implicates several interaction networks comprising a "stemness" signature in the
      most primitive hematopoietic stem cell (HSC) populations, as well as "myeloid"
      patterns associated with two branches of myeloid development. 

PMID- 24747945
TI  - Nrf2 enhances myocardial clearance of toxic ubiquitinated proteins.
AB  - Nuclear factor erythroid-2 related factor 2 (Nrf2) is a master transcription
      factor that controls the basal and inducible expression of a battery of
      antioxidant genes and other cytoprotective phase II detoxifying enzymes. While
      knockout of Nrf2 exaggerates cardiac pathological remodeling and dysfunction in
      diverse pathological settings, pharmacological activation of Nrf2 protects
      against cardiomyocyte injury and cardiac dysfunction. In contrast, there is also
      a concern that the chronic activation of Nrf2 secondary to oxidative stress is a
      contributing mechanism for the reductive stress-mediated heart failure. However,
      a direct link between cardiac specific activation of Nrf2 and cardiac protection
      or dysfunction in vivo remains to be established. Therefore, we investigated the
      effect of cardiomyocyte-specific transgenic activation of Nrf2 (Nrf2(ctg)) on
      cardiac pathological remodeling and dysfunction. We found that the cardiomyocyte
      specific activation of Nrf2 suppressed myocardial oxidative stress as well as
      cardiac apoptosis, fibrosis, hypertrophy, and dysfunction in a setting of
      sustained pressure overload induced by transverse aortic arch constriction (TAC)
      in mice. Notably, the constitutive activation of Nrf2 increased the steady level
      of autophagosomes while decreasing the ubiquitinated protein aggregates in the
      heart after TAC. Nrf2 gene gain- and loss-of-function approaches revealed that
      Nrf2 enhances autophagosome formation and autophagic flux in cardiomyocytes.
      Unexpectedly, while Nrf2 minimally regulated apoptosis, it suppressed
      significantly the proteotoxic necrosis in cardiomyocytes. In addition, Nrf2
      attenuated the proteocytotoxicity presumably via enhancing autophagy-mediated
      clearance of ubiquitinated protein aggregates in cardiomyocytes. Taken together,
      we demonstrated for the first time that cardiac specific activation of Nrf2
      suppresses cardiac maladaptive remodeling and dysfunction most likely by
      enhancing autophagic clearance of toxic protein aggregates in the heart. 

PMID- 24747946
TI  - Normal appearing and diffusely abnormal white matter in patients with multiple
      sclerosis assessed with quantitative MR.
AB  - INTRODUCTION: Magnetic Resonance Imaging is a sensitive technique for detecting
      white matter (WM) MS lesions, but the relation with clinical disability is low.
      Because of this, changes in both 'normal appearing white matter' (NAWM) and
      'diffusely abnormal white matter' (DAWM) have been of interest in recent years.
      MR techniques, including quantitative magnetic resonance imaging (qMRI) and
      quantitative magnetic resonance spectroscopy (qMRS), have been developed in order
      to detect and quantify such changes. In this study, qMRI and qMRS were used to
      investigate NAWM and DAWM in typical MS patients and in MS patients with low
      number of WM lesions. Patient data were compared to 'normal white matter' (NWM)
      in healthy controls. METHODS: QMRI and qMRS measurements were performed on a 1.5
      T Philips MR-scanner. 35 patients with clinically definite MS and 20 healthy
      controls were included. Twenty of the patients fulfilled the 'Barkhof-Tintore
      criteria' for MS, ('MRIpos'), whereas 15 showed radiologically atypical findings
      with few WM lesions ('MRIneg'). QMRI properties were determined in ROIs of NAWM,
      DAWM and lesions in the MS groups and of NWM in controls. Descriptive statistical
      analysis and comparisons were performed. Correlations were calculated between
      qMRI measurements and (1) clinical parameters and (2) WM metabolite
      concentrations. Regression analyses were performed with brain parenchyma fraction
      and MSSS. RESULTS: NAWM in the MRIneg group was significantly different from NAWM
      in the MRIpos group and NWM. In addition, R1 and R2 of NAWM in the MRIpos group
      correlated negatively with EDSS and MSSS. DAWM was significantly different from
      NWM, but similar in the MS groups. N-acetyl aspartate correlated negatively with
      R1 and R2 in MRIneg. R2 of DAWM was associated with BPF. CONCLUSIONS: Changes in
      NAWM and DAWM are independent pathological entities in the disease. The
      correlation between qMRI and clinical status may shed new light on the
      clinicoradiological paradox.

PMID- 24747947
TI  - Induction of A. fumigatus-specific CD4-positive T cells in patients recovering
      from invasive aspergillosis.
AB  - After allogeneic stem cell transplantation patients are at risk of invasive
      aspergillosis, especially during the period of neutropenia. Recent data suggest
      that impaired T-cell immune reconstitution after transplantation plays an
      important role in this increased risk. In this study we investigated whether
      Aspergillus-specific T cells are involved in the recovery from invasive
      aspergillosis by analyzing the Aspergillus-specific T-cell response in patients
      with invasive aspergillosis. In nine patients whose Aspergillus infection
      improved, we identified Crf1- or Catalase1-specific T cells on the basis of CD154
      expression and interferon-gamma production following stimulation with overlapping
      peptides of the A. fumigatus proteins Crf1 and Catalase1. These Aspergillus
      specific T cells were induced at the moment of regression of the aspergillus
      lesions. Crf1- and Catalase1-specific T cells, sorted on the basis of CD154
      expression at the peak of the immune response, had a T helper-1 phenotype and
      recognized a variety of T-cell epitopes. In contrast, in two patients with
      progressive invasive aspergillosis, no Crf1- or Catalase1-specific T cells were
      identified. These data indicate that the presence of Aspergillus-specific T cells
      with a T helper-1 phenotype correlates with the clearance of aspergillus
      infection. 

PMID- 24747948
TI  - Clinical diagnosis and typing of systemic amyloidosis in subcutaneous fat
      aspirates by mass spectrometry-based proteomics.
AB  - Examination of abdominal subcutaneous fat aspirates is a practical, sensitive and
      specific method for the diagnosis of systemic amyloidosis. Here we describe the
      development and implementation of a clinical assay using mass spectrometry-based
      proteomics to type amyloidosis in subcutaneous fat aspirates. First, we validated
      the assay comparing amyloid-positive (n=43) and -negative (n=26) subcutaneous fat
      aspirates. The assay classified amyloidosis with 88% sensitivity and 96%
      specificity. We then implemented the assay as a clinical test, and analyzed 366
      amyloid-positive subcutaneous fat aspirates in a 4-year period as part of routine
      clinical care. The assay had a sensitivity of 90%, and diverse amyloid types,
      including immunoglobulin light chain (74%), transthyretin (13%), serum amyloid A
      (%1), gelsolin (1%), and lysozyme (1%), were identified. Using bioinformatics, we
      identified a universal amyloid proteome signature, which has high sensitivity and
      specificity for amyloidosis similar to that of Congo red staining. We curated
      proteome databases which included variant proteins associated with systemic
      amyloidosis, and identified clonotypic immunoglobulin variable gene usage in
      immunoglobulin light chain amyloidosis, and the variant peptides in hereditary
      transthyretin amyloidosis. In conclusion, mass spectrometry-based proteomic
      analysis of subcutaneous fat aspirates offers a powerful tool for the diagnosis
      and typing of systemic amyloidosis. The assay reveals the underlying pathogenesis
      by identifying variable gene usage in immunoglobulin light chains and the variant
      peptides in hereditary amyloidosis. 

PMID- 24747949
TI  - Rituximab and three dexamethasone cycles provide responses similar to splenectomy
      in women and those with immune thrombocytopenia of less than two years duration.
AB  - Adults with newly diagnosed or persistent immunothrombocytopenia frequently
      relapse upon tapering steroids; adults and children with chronic disease have an
      even lower likelihood of lasting response. In adults with newly-diagnosed
      immunothrombocytopenia, two studies showed that dexamethasone 40 mg/day * four
      days and 4 rituximab infusions were superior to dexamethasone alone. Studies have
      also shown three cycles of dexamethasone are better than one and patients with
      persistent/chronic immunothrombocytopenia respond less well to either
      dexamethasone or rituximab. Therefore, 375 mg/m(2) * 4 rituximab was combined
      with three 4-day cycles of 28 mg/m(2) (max. 40 mg) dexamethasone at 2-week
      intervals and explored in 67 ITP patients. Best long-term response was assessed
      as complete (platelet count >= 100 * 10(9)/L) or partial (50-99 * 10(9)/L). Only
      5 patients had not been previously treated. Fifty achieved complete (n=43, 64%)
      or partial (n=7, 10%) responses. Thirty-five of 50 responders maintained
      treatment-free platelet counts over 50 * 10(9)/L at a median 17 months (range 4
      67) projecting 44% event-free survival. Duration of immunothrombocytopenia less
      than 24 months, achieving complete responses, and being female were associated
      with better long-term response (P<0.01). Adverse events were generally mild
      moderate, but 3 patients developed serum sickness and 2 colitis; there were no
      sequelae. Dexamethasone could be difficult to tolerate. Fourteen patients became
      hypogammaglobulinemic and half had increased frequency of minor infections; 9 of
      12 evaluable patients recovered their IgG levels. Rituximab combined with three
      cycles of dexamethasone provides apparently better results to reported findings
      with rituximab alone, dexamethasone alone, or the combination with one cycle of
      dexamethasone. The results suggest medical cure may be achievable in
      immunothrombocytopenia, especially in women and in patients within two years of
      diagnosis. (clinicaltrials.gov identifier:02050581).

PMID- 24747950
TI  - Targeted shRNA screening identified critical roles of pleckstrin-2 in
      erythropoiesis.
AB  - Differentiation of erythroblasts to mature red blood cells involves dynamic
      changes of the membrane and cytoskeleton networks that are not fully
      characterized. Using a mouse fetal liver erythroblast culture system and a
      targeted shRNA functional screening strategy, we identified a critical role of
      pleckstrin-2 in actin dynamics and protection of early stage terminal
      erythroblasts from oxidative damage. Knockdown of pleckstrin-2 in the early stage
      of terminal erythropoiesis disrupted the actin cytoskeleton and led to
      differentiation inhibition and apoptosis. This pro-survival and differentiation
      function of pleckstrin-2 was mediated through its interaction with cofilin, by
      preventing cofilin's mitochondrial entry when the intracellular level of reactive
      oxygen species was higher in the early stage of terminal erythropoiesis.
      Treatment of the cells with a scavenger of reactive oxygen species rescued
      cofilin's mitochondrial entry and differentiation inhibition induced by
      pleckstrin-2 knockdown. In contrast, pleckstrin-2 knockdown in late stage
      terminal erythroblasts had no effect on survival or differentiation but blocked
      enucleation due to disorganized actin cytoskeleton. Thus, our study identified a
      dual function of pleckstrin-2 in the early and late stages of terminal
      erythropoiesis through its regulations of actin dynamics and cofilin's
      mitochondrial localization, which reflects intracellular level of reactive oxygen
      species in different developmental stages. 

PMID- 24747951
TI  - Predictors of extra-marital partnerships among women married to fishermen along
      Lake Victoria in Kisumu County, Kenya.
AB  - BACKGROUND: The vulnerability of women to HIV infection makes establishing
      predictors of women's involvement in extra-marital partnerships critical. We
      investigated the predictors of extra-marital partnerships among women married to
      fishermen. METHODS: The current analyses are part of a mixed methods cross
      sectional survey of 1090 gender-matched interviews with 545 couples and 12 focus
      group discussions (FGDs) with 59 couples. Using a proportional to size simple
      random sample of fishermen as our index participants, we asked them to enrol in
      the study with their spouses. The consenting couples were interviewed
      simultaneously in separate private rooms. In addition to socio-economic and
      demographic data, we collected information on sexual behaviour including extra
      marital sexual partnerships. We analysed these data using descriptive statistics
      and multivariate logistic regression. For FGDs, couples willing to participate
      were invited, consented and separated for simultaneous FGDs by gender-matched
      moderators. The resultant audiofiles were transcribed verbatim and translated
      into English for coding and thematic content analysis using NVivo 9. RESULTS: The
      prevalence of extra-marital partnerships among women was 6.2% within a reference
      time of six months. Factors that were independently associated with increased
      likelihood of extra-marital partnerships were domestic violence (aOR, 1.45; 95%
      CI 1.09-1.92), women reporting being denied a preferred sex position (aOR, 3.34;
      95% CI 1.26-8.84) and spouse longer erect penis (aOR, 1.34; 95% CI 1.00-1.78).
      Conversely, women's age--more than 24 years (aOR, 0.33; 95% CI 0.14-0.78) and
      women's increased sexual satisfaction (aOR, 0.92; 95% CI 0.87-0.96) were
      associated with reduced likelihood of extra-marital partnerships. CONCLUSION:
      Domestic violence, denial of a preferred sex positions, longer erect penis,
      younger age and increased sexual satisfaction were the main predictors of women's
      involvement in extra-marital partnerships. Integration of sex education,
      counselling and life skills training in couple HIV prevention programs might help
      in risk reduction.

PMID- 24747952
TI  - The rice endosperm ADP-glucose pyrophosphorylase large subunit is essential for
      optimal catalysis and allosteric regulation of the heterotetrameric enzyme.
AB  - Although an alternative pathway has been suggested, the prevailing view is that
      starch synthesis in cereal endosperm is controlled by the activity of the
      cytosolic isoform of ADPglucose pyrophosphorylase (AGPase). In rice, the
      cytosolic AGPase isoform is encoded by the OsAGPS2b and OsAGPL2 genes, which code
      for the small (S2b) and large (L2) subunits of the heterotetrameric enzyme,
      respectively. In this study, we isolated several allelic missense and nonsense
      OsAGPL2 mutants by N-methyl-N-nitrosourea (MNU) treatment of fertilized egg cells
      and by TILLING (Targeting Induced Local Lesions in Genomes). Interestingly, seeds
      from three of the missense mutants (two containing T139I and A171V) were severely
      shriveled and had seed weight and starch content comparable with the shriveled
      seeds from OsAGPL2 null mutants. Results from kinetic analysis of the purified
      recombinant enzymes revealed that the catalytic and allosteric regulatory
      properties of these mutant enzymes were significantly impaired. The missense
      heterotetramer enzymes and the S2b homotetramer had lower specific (catalytic)
      activities and affinities for the activator 3-phosphoglycerate (3-PGA). The
      missense heterotetramer enzymes showed more sensitivity to inhibition by the
      inhibitor inorganic phosphate (Pi) than the wild-type AGPase, while the S2b
      homotetramer was profoundly tolerant to Pi inhibition. Thus, our results provide
      definitive evidence that starch biosynthesis during rice endosperm development is
      controlled predominantly by the catalytic activity of the cytoplasmic AGPase and
      its allosteric regulation by the effectors. Moreover, our results show that the
      L2 subunit is essential for both catalysis and allosteric regulatory properties
      of the heterotetramer enzyme. 

PMID- 24747953
TI  - A microautoradiographic method for fresh-frozen sections to reveal the
      distribution of radionuclides at the cellular level in plants.
AB  - Microautoradiography (MAR) is a conventional imaging method based on the
      daguerreotype. The technique is used to visualize the distribution of
      radionuclide-labeled compounds within a tissue section. However, application of
      the classical MAR method to plant tissue sections is associated with several
      difficulties. In this study, we report an MAR method applicable to fresh-frozen
      plant sections. Our method had two features: (i) the sample was kept frozen from
      plant tissue collection to radioisotope detection, making it possible to fix
      solutes without solvent exchange; and (ii) 1.2 um thick polyphenylene sulfide
      film was inserted between the fresh-frozen plant section and the photosensitive
      nuclear emulsion to separate the section from the emulsion before autoradiography
      was conducted, which significantly improved the quality of the section until
      microscopic detection, the quality of the MAR image and the success rate. Then,
      the passage of cadmium (Cd) through vegetative rice stem tissue after 24 h of
      (109)Cd absorption was described for the first time using the MAR method. MAR
      clearly revealed the distribution of (109)Cd at the tissue level with high
      resolution. The (109)Cd concentration in phloem cells was found to be
      particularly high, whereas the xylem cells contained only small amounts of
      (109)Cd. The MAR method was also applicable for detecting (109)Cd and
      [(33)P]phosphate in roots. The MAR method developed here is expected to provide
      distribution images for a variety of compounds and ions in plant tissue. 

PMID- 24747954
TI  - Glucitol dehydrogenase from peach (Prunus persica) fruits is regulated by
      thioredoxin h.
AB  - Glucitol (Gol) is a major photosynthetic product in plants from the Rosaceae
      family. Herein we report the molecular cloning, heterologous expression and
      characterization of Gol dehydrogenase (GolDHase, EC 1.1.1.14) from peach (Prunus
      persica) fruits. The recombinant enzyme showed kinetic parameters similar to
      those reported for orthologous enzymes purified from apple and pear fruits. The
      activity of recombinant GolDHase was strongly inhibited by Cu(2+) and Hg(2+),
      suggesting that it might have cysteine residues critical for functionality.
      Oxidizing compounds (such as diamide, hydrogen peroxide and oxidized glutathione)
      inactivated the enzyme, whereas its activity was restored after incubation with
      reduced glutathione and thioredoxin from Escherichia coli. Recombinant
      thioredoxin h from peach fruits also recovered the activity of oxidized GolDHase.
      Our results suggest that peach fruit GolDHase could be redox regulated in vivo
      and this would be of relevance to determine carbon assimilation and partitioning
      in plants accumulating sugar alcohols. 

PMID- 24747955
TI  - Determination of the spontaneous locomotor activity in Drosophila melanogaster.
AB  - Drosophila melanogaster has been used as an excellent model organism to study
      environmental and genetic manipulations that affect behavior. One such behavior
      is spontaneous locomotor activity. Here we describe our protocol that utilizes
      Drosophila population monitors and a tracking system that allows continuous
      monitoring of the spontaneous locomotor activity of flies for several days at a
      time. This method is simple, reliable, and objective and can be used to examine
      the effects of aging, sex, changes in caloric content of food, addition of drugs,
      or genetic manipulations that mimic human diseases. 

PMID- 24747956
TI  - Improvement of sensitivity in sentinel lymph node procedure in melanoma patients.

PMID- 24747957
TI  - Reproducibility of in-vivo OCT measured three-dimensional human lamina cribrosa
      microarchitecture.
AB  - PURPOSE: To determine the reproducibility of automated segmentation of the three
      dimensional (3D) lamina cribrosa (LC) microarchitecture scanned in-vivo using
      optical coherence tomography (OCT). METHODS: Thirty-nine eyes (8 healthy, 19
      glaucoma suspects and 12 glaucoma) from 49 subjects were scanned twice using
      swept-source (SS-) OCT in a 3.5*3.5*3.64 mm (400*400*896 pixels) volume centered
      on the optic nerve head, with the focus readjusted after each scan. The LC was
      automatically segmented and analyzed for microarchitectural parameters, including
      pore diameter, pore diameter standard deviation (SD), pore aspect ratio, pore
      area, beam thickness, beam thickness SD, and beam thickness to pore diameter
      ratio. Reproducibility of the parameters was assessed by computing the
      imprecision of the parameters between the scans. RESULTS: The automated
      segmentation demonstrated excellent reproducibility. All LC microarchitecture
      parameters had an imprecision of less or equal to 4.2%. There was little
      variability in imprecision with respect to diagnostic category, although the
      method tends to show higher imprecision amongst healthy subjects. CONCLUSION: The
      proposed automated segmentation of the LC demonstrated high reproducibility for
      3D LC parameters. This segmentation analysis tool will be useful for in-vivo
      studies of the LC.

PMID- 24747958
TI  - Expression and recruitment of uracil-DNA glycosylase are regulated by E2A during
      antibody diversification.
AB  - B-lymphocytes can modify their immunoglobulin (Ig) genes to generate specific
      antibodies with a new isotype and enhanced affinity against an antigen.
      Activation-induced cytidine deaminase (AID), which is positively regulated by the
      transcription factor E2A, is the key enzyme that initiates these processes by
      deaminating cytosine to uracil in Ig genes. Nuclear uracil-DNA glycosylase (UNG2)
      is subsequently required for uracil processing in the generation of high affinity
      antibodies of different isotypes. Here we show that the transcription factor E2A
      binds to the UNG2 promoter and represses UNG2 expression. Inhibition of E2A by
      binding of Ca(2+)-activated calmodulin alleviates this repression. Furthermore,
      we demonstrate that UNG2 preferentially accumulates in regions of the Ig heavy
      chain (IgH) gene containing AID hotspots. Calmodulin inhibition of E2A strongly
      enhances this UNG2 accumulation, indicating that it is negatively regulated by
      E2A as well. We show also that over-expression of E2A can suppress class switch
      recombination. The results suggest that E2A is a key factor in regulating the
      balance between AID and UNG2, both at expression and Ig targeting levels, to
      stimulate Ig diversification and suppress normal DNA repair processes.

PMID- 24747959
TI  - Liver X receptor regulates mouse GM-CSF-derived dendritic cell differentiation in
      vitro.
AB  - Liver X receptors (LXRs) are nuclear receptors that play an essential role in
      lipid and cholesterol metabolism. Emerging studies indicate a potential function
      for LXRs in regulating dendritic cell (DC)-dependent immune responses; however,
      the role of LXRs in DC differentiation is largely unknown. Here, we report that
      LXRalpha regulates the differentiation of mouse GM-CSF-derived DCs. Activation or
      overexpression of LXRalpha significantly enhanced myeloid DC differentiation from
      mouse bone marrow (BM) cells, while siRNA-mediated knockdown of LXRalpha
      suppressed DC differentiation. In addition, we demonstrated that LXR agonist
      programmed DCs showed an increased capacity for stimulating T-cell proliferation.
      Mechanistic studies showed that activation of LXR could inhibit the
      phosphorylation of STAT3 and downregulate the expression of its target, S100A9,
      an important negative regulator of myeloid DC differentiation. We also found that
      Histone deacetylase (HDAC) inhibition interfered with the effect of LXR on STAT3
      signaling via acetylation of STAT3. Chromatin immunoprecipitation assays
      confirmed that LXR activation and HDAC inhibition balanced the recruitment of
      STAT3 to the S100A9 promoter, which involved distinct post-translational
      modifications of STAT3. In conclusion, our observations demonstrated a novel role
      for LXRalpha in GM-CSF-derived DC differentiation and revealed the underlying
      mechanism.

PMID- 24747960
TI  - Divergent roles of histone deacetylase 6 (HDAC6) and histone deacetylase 11
      (HDAC11) on the transcriptional regulation of IL10 in antigen presenting cells.
AB  - The anti-inflammatory cytokine IL-10 is a key modulator of immune responses. A
      better understanding of the regulation of this cytokine offers the possibility of
      tipping the balance of the immune response toward either tolerance, or enhanced
      immune responses. Histone deacetylases (HDACs) have been widely described as
      negative regulators of transcriptional regulation, and in this context, the
      primarily nuclear protein HDAC11 was shown to repress il-10 gene transcriptional
      activity in antigen-presenting cells (APCs). Here we report that another HDAC,
      HDAC6, primarily a cytoplasmic protein, associates with HDAC11 and modulates the
      expression of IL-10 as a transcriptional activator. To our knowledge, this is the
      first demonstration of two different HDACs being recruited to the same gene
      promoter to dictate divergent transcriptional responses. This dynamic interaction
      results in dynamic changes in the expression of IL-10 and might help to explain
      the intrinsic plasticity of the APC to determine T-cell activation versus T-cell
      tolerance.

PMID- 24747962
TI  - Uptake and transfer of a Bt toxin by a Lepidoptera to its eggs and effects on its
      offspring.
AB  - Research on non-target effects of transgenic crop plants has focused primarily on
      bitrophic, tritrophic and indirect effects of entomotoxins from Bacillus
      thuringiensis, but little work has considered intergenerational transfer of Cry
      proteins. This work reports a lepidopteran (Chlosyne lacinia) taking up a Bt
      entomotoxin when exposed to sublethal or low concentrations, transferring the
      entomotoxin to eggs, and having adverse effects on the first filial generation
      (F1) offspring. Two bioassays were conducted using a sublethal concentration of
      toxin (100.0 ng/ul Cry1Ac) for adults and a concentration equal to the LC10 (2.0
      ng/ul Cry1Ac) for larvae. Cry1Ac is the most common entomotoxin expressed in Bt
      cotton in Brazil. In the adult diet bioassay there was no adverse effect on the
      parental generation (P0) adults, but the F1 larvae had higher mortality and
      longer development time compared to F1 larvae of parents that did not ingest
      Cry1Ac. For the 3rd instar larvae, there was no measurable effect on the P0
      larvae, pupae and adults, but the F1 larvae had higher mortality and longer
      development time. Using chemiluminescent Western Blot, Cry1Ac was detected in F1
      eggs laid by P0 butterflies from both bioassays. Our study indicates that, at
      least for this species and these experimental conditions, a ~65 kDa insecticidal
      protein can be taken up and transferred to descendants where it can increase
      mortality and development time. 

PMID- 24747961
TI  - An expanding universe of the non-coding genome in cancer biology.
AB  - Neoplastic transformation is caused by accumulation of genetic and epigenetic
      alterations that ultimately convert normal cells into tumor cells with
      uncontrolled proliferation and survival, unlimited replicative potential and
      invasive growth [Hanahan,D. et al. (2011) Hallmarks of cancer: the next
      generation. Cell, 144, 646-674]. Although the majority of the cancer studies have
      focused on the functions of protein-coding genes, emerging evidence has started
      to reveal the importance of the vast non-coding genome, which constitutes more
      than 98% of the human genome. A number of non-coding RNAs (ncRNAs) derived from
      the 'dark matter' of the human genome exhibit cancer-specific differential
      expression and/or genomic alterations, and it is increasingly clear that ncRNAs,
      including small ncRNAs and long ncRNAs (lncRNAs), play an important role in
      cancer development by regulating protein-coding gene expression through diverse
      mechanisms. In addition to ncRNAs, nearly half of the mammalian genomes consist
      of transposable elements, particularly retrotransposons. Once depicted as selfish
      genomic parasites that propagate at the expense of host fitness, retrotransposon
      elements could also confer regulatory complexity to the host genomes during
      development and disease. Reactivation of retrotransposons in cancer, while
      capable of causing insertional mutagenesis and genome rearrangements to promote
      oncogenesis, could also alter host gene expression networks to favor tumor
      development. Taken together, the functional significance of non-coding genome in
      tumorigenesis has been previously underestimated, and diverse transcripts derived
      from the non-coding genome could act as integral functional components of the
      oncogene and tumor suppressor network.

PMID- 24747963
TI  - Identification and control of a Pseudomonas spp (P. fulva and P. putida)
      bloodstream infection outbreak in a teaching hospital in Beijing, China.
AB  - OBJECTIVES: An outbreak of bacteremia caused by Pseudomonas spp (P. fulva and P.
      putida) was first identified in our hospital in the summer of 2010 and reoccurred
      in the following year. Based on the epidemiological data collected in these 2
      years, we initiated an investigation on the source of the outbreak. The aim of
      this study was to report the results of the investigation, as well as the
      intervention strategies that resulted in successful control of the outbreak.
      METHODS: An infection control team was set up consisting of infectious disease
      specialists, microbiologists, infection control practitioners, and head nurses.
      The microbiology and medical records of case-patients with P. fulva or P. putida
      bloodstream infections were reviewed. Environmental samples and intravenous (IV)
      solutions from the wards and the pharmacy center were collected for culturing.
      The molecular characteristics of the bacterial isolates were studied by pulsed
      field gel electrophoresis (PFGE). Strict infection control strategies were
      implemented. RESULTS: A total of 20 case-patients from five inpatient wards were
      identified during three summer seasons from 2010 to 2012. Nineteen of them
      recovered with proper antibiotics. Unfortunately one died from complications of
      heart failure. A total of 19 isolates of P. fulva and four of P. putida were
      identified, of which 20 were from blood, two from environmental surface samples
      from the hospital pharmacy, and one from an in-use compounded solution from a
      case-patient in the cardiology ward. Molecular analysis revealed that the P.
      fulva isolated from the in-use compounded solution (5% glucose solution
      containing insulin, isosorbide dinitrate, and potassium magnesium aspartate) and
      the environmental samples had the same PFGE type as the clinical isolates.
      CONCLUSIONS: The investigation identified that contaminated IV solution was the
      source of the P. fulva bacteremia, which prompted us to implement intensified
      control measures that resulted in successful control of the outbreak.

PMID- 24747964
TI  - Vaccination influences the evolution of classical swine fever virus.
AB  - Classical swine fever is a serious, economically damaging disease caused by
      classical swine fever virus (CSFV). The CSFV is composed of two clades, according
      to phylogenetic estimates. Attenuated live vaccine such as HCLV, has been widely
      used to protect pigs from CSFV, but the influence of vaccination on the evolution
      of CSFV has not been studied. We conducted a systemic analysis of the impact of
      vaccination on the evolution of CSFV by comparing vaccine-related and non-vaccine
      related CSFV groups. We found that vaccination may affect strain diversity and
      immune escape through recombination and point mutation. We also found that
      vaccination may influence the population dynamics, evolutionary rate and adaptive
      evolution of classical swine fever virus. Our evidence suggests that the
      vaccination might also change host adaptation through influencing codon usage of
      the virus in swine. These findings suggest that it is necessary to avoid
      excessive use of CSFV attenuated vaccines. 

PMID- 24747965
TI  - Distinct evolutionary origins of G12P[8] and G12P[9] group A rotavirus strains
      circulating in Brazil.
AB  - G12 group A rotavirus (RVA) are currently recognized as a globally emerging
      genotype and have been described in combination with several P-types. In Brazil,
      G12 RVA strains have been described in the Southern (2003) and Northern (2008
      2010) regions, in combination with the P[9] and P[6] genotype, respectively. To
      date, few complete genomes of G12 RVA strains have been described (none from
      Brazilian strains), considering G12P[9] genotype just one strain, RVA/Human
      tc/THA/T152/1998/G12P[9], has their 11 gene segments characterized. This study
      aims to determine the genomic constellation of G12P[9] and G12P[8] RVA strains
      detected in Brazil between 2006 and 2011. Therefore, the eleven gene segments of
      five Brazilian G12 RVA strains were amplified and sequenced, and the genotype of
      each gene segment was assigned using phylogenetic analysis. Complete genome
      analyses of G12 RVA strain circulating between 2006 and 2011 in Brazil revealed a
      conserved Wa-like genomic constellation for three G12P[8] RVA strains; whereas
      the two G12P[9] strains possessed distinct reassorted AU-1-like genomic
      constellations, closely related to the reference strain RVA/Human
      tc/THA/T152/1998/G12P[9] in most genes. The results obtained in the current study
      suggest that G12P[9] (AU-1-like) and G12P[8] (Wa-like) strains detected in
      different regions of Brazil do not share a common origin. Moreover, while
      Brazilian G12P[8] RVA strains showed a complete Wa-like human constellation, both
      G12P[9] strains possessed an NSP1 gene of bovine origin (NSP1), and RVA/Human
      wt/BRA/PE18974/2010/G12P[9] also possessed a VP3 gene of canine/feline origin. 

PMID- 24747966
TI  - Glioma-specific Domain IV EGFR cysteine mutations promote ligand-induced covalent
      receptor dimerization and display enhanced sensitivity to dacomitinib in vivo.
AB  - A feature of many gliomas is the amplification of the epidermal growth factor
      receptor (EGFR), resulting in its overexpression. Missense mutations or deletions
      within the extracellular domain are associated with this amplification and can
      lead to constitutive activation of the receptor, with the Domain I/II deletion,
      EGFRvIII, being the most common. These changes have also been associated with
      increased sensitivity to EGFR inhibition using small molecule inhibitors. We have
      expressed, in human glioma cells, EGFR containing four glioma-specific EGFR
      missense mutations within Domain IV (C620Y, C624F, C628Y and C636Y) to analyze
      their biological properties and sensitivity to EGFR inhibition. One of these
      mutants, C620Y, exhibited an enhanced basal phosphorylation, which was partially
      dependent on an EGFR-ligand autocrine loop. All Domain IV mutants responded
      equally as well as wildtype EGFR (wtEGFR) to ligand stimulation. Biochemical
      analysis revealed that a pre-formed, disulfide-bonded dimer associated with these
      mutations was underglycosylated, inactive and cytoplasmically retained. Ligand
      stimulation resulted in the formation of a tyrosine-phosphorylated, disulfide
      bonded dimer for all Domain IV mutants but not for wtEGFR. Following treatment
      with the next-generation, irreversible pan-ErbB inhibitor dacomitinib, the C620Y,
      C624F and EGFRvIII mutants were inactivated, covalently dimerized and were
      retained in the cytoplasm, resulting in cell-surface receptor loss and, for C620Y
      and C624F, decreased binding of EGF. Dacomitinib treatment significantly reduced
      the in vivo growth of human glioma xenografts bearing C620Y, but not wtEGFR.
      Collectively, these data indicate that the unique biochemical traits of Domain IV
      EGFR cysteine mutants can be exploited for enhanced sensitivity to EGFR small
      molecule inhibitors, with potential clinical applications. 

PMID- 24747967
TI  - IL-13Ralpha2 mediates PNR-induced migration and metastasis in ERalpha-negative
      breast cancer.
AB  - Emerging evidence has linked photoreceptor cell-specific nuclear receptor
      (PNR/NR2E3), an orphan nuclear hormone receptor, to human breast cancer. PNR was
      shown to be a transcriptional activator of estrogen receptor-alpha (ERalpha) in
      ERalpha-positive breast cancer cell lines and high-level expression of PNR
      correlates with favorable response of ERalpha-positive breast cancer patients to
      tamoxifen. Interestingly, gene expression microarray study shows that PNR
      regulates distinct genes from those regulated by ERalpha, suggesting that PNR
      could have ERalpha-independent functions. Herein, we investigated the function of
      PNR in ERalpha-negative breast cancer cells. Our results showed that PNR-induced
      cell migration and metastasis of ERalpha-negative breast cancer cells both in
      vitro and in vivo, and the effect was attributed to the upregulation of
      interleukin (IL)-13Ralpha2, a high-affinity receptor for IL-13 that regulates
      tumor growth, invasion and metastasis of various human cancers. Mechanistically,
      PNR activated transcription of IL-13Ralpha2 through direct recruitment to IL
      13Ralpha2 promoter. Upon stimulation with IL-13, IL-13Ralpha2 increased the
      extracellular signal-regulated kinases 1 and 2 phosphorylation, which led to
      breast cancer migration and metastasis. The IL-13 triggered signal cascade was
      specific to IL-13Ralpha2, as the closely related IL-13Ralpha1 was not regulated
      by PNR. IL-13Ralpha2 is a novel tumor antigen that is overexpressed in a variety
      of solid tumor types. This study presents the first evidence that PNR could
      promote ERalpha-negative breast cancer metastasis through activation of IL
      13Ralpha2-mediated signaling pathway. 

PMID- 24747968
TI  - Two mature products of MIR-491 coordinate to suppress key cancer hallmarks in
      glioblastoma.
AB  - MIR-491 is commonly co-deleted with its adjacent CDKN2A on chromosome 9p21.3 in
      glioblastoma multiforme (GBM). However, it is not known whether deletion of MIR
      491 is only a passenger event or has an important role. Small-RNA sequencing of
      samples from GBM patients demonstrated that both mature products of MIR-491 (miR
      491-5p and -3p) are downregulated in tumors compared with the normal brain. The
      integration of GBM data from The Cancer Genome Atlas (TCGA), miRNA target
      prediction and reporter assays showed that miR-491-5p directly targets EGFR, CDK6
      and Bcl-xL, whereas miR-491-3p targets IGFBP2 and CDK6. Functionally, miR-491-3p
      inhibited glioma cell invasion; overexpression of both miR-491-5p and -3p
      inhibited proliferation of glioma cell lines and impaired the propagation of
      glioma stem cells (GSCs), thereby prolonging survival of xenograft mice.
      Moreover, knockdown of miR-491-5p in primary Ink4a-Arf-null mouse glial
      progenitor cells exacerbated cell proliferation and invasion. Therefore, MIR-491
      is a tumor suppressor gene that, by utilizing both mature forms, coordinately
      controls the key cancer hallmarks: proliferation, invasion and stem cell
      propagation. 

PMID- 24747969
TI  - MUC4 regulates cellular senescence in head and neck squamous cell carcinoma
      through p16/Rb pathway.
AB  - The limited effectiveness of therapy for patients with advanced stage head and
      neck squamous cell carcinoma (HNSCC) or recurrent disease is a reflection of an
      incomplete understanding of the molecular basis of HNSCC pathogenesis. MUC4, a
      high molecular weight glycoprotein, is differentially overexpressed in many human
      cancers and implicated in cancer progression and resistance to several
      chemotherapies. However, its clinical relevance and the molecular mechanisms
      through which it mediates HNSCC progression are not well understood. This study
      revealed a significant upregulation of MUC4 in 78% (68/87) of HNSCC tissues
      compared with 10% positivity (1/10) in benign samples (P=0.006, odds ratio (95%
      confidence interval)=10.74 (2.0-57.56). MUC4 knockdown (KD) in SCC1 and SCC10B
      HNSCC cell lines resulted in significant inhibition of growth in vitro and in
      vivo, increased senescence as indicated by an increase in the number of flat,
      enlarged and senescence-associated beta-galactosidase (SA-beta-Gal)-positive
      cells. Decreased cellular proliferation was associated with G0/G1 cell cycle
      arrest and decrease expression of cell cycle regulatory proteins like cyclin E,
      cyclin D1 and decrease in BrdU incorporation. Mechanistic studies revealed
      upregulation of p16, pRb dephosphorylation and its interaction with histone
      deacetylase 1/2. This resulted in decreased histone acetylation (H3K9) at cyclin
      E promoter leading to its downregulation. Orthotopic implantation of MUC4 KD SCC1
      cells into the floor of the mouth in nude mice resulted in the formation of
      significantly smaller tumors (170+/-18.30 mg) compared to those (375+/-17.29 mg)
      formed by control cells (P=0.00007). In conclusion, our findings showed that MUC4
      overexpression has a critical role by regulating proliferation and cellular
      senescence of HNSCC cells. Downregulation of MUC4 may be a promising therapeutic
      approach for treating HNSCC patients.

PMID- 24747970
TI  - Ubiquilin1 represses migration and epithelial-to-mesenchymal transition of human
      non-small cell lung cancer cells.
AB  - Ubiquilin1 (UBQLN1) is a ubiquitin-like domain and a ubiquitin-associated domain
      containing protein that has been reported to be involved in shuttling proteins to
      the proteasome, especially during endoplasmic reticulum-associated protein
      degradation. Thus, UBQLN1 function has been shown to be critical for combating a
      number of neurological disorders caused by protein aggregation, such as
      amyotrophic lateral sclerosis, Alzheimer's disease and Huntington's disease. A
      role for UBQLN1 in regulating processes involved in tumorigenesis has not been
      demonstrated. Herein, we show that loss of UBQLN1 causes increased cell migration
      and invasion, actin cytoskeleton reorganization and induction of epithelial-to
      mesenchymal transition (EMT). Loss of UBQLN1 results in a significant decrease in
      the expression of epithelial markers including E-cadherin and claudin1, whereas
      expression of mesenchymal markers including Vimentin, Snail and ZEB1 are
      significantly elevated. Interestingly, we found that ZEB1 is required for
      induction of mesenchymal-like properties following loss of UBQLN1 and ZEB1 is
      capable of repressing expression of UBQLN1, suggesting a physiological,
      reciprocal regulation of EMT by UBQLN1 and ZEB1. Further, we find evidence for a
      role for UBQLN2 in also regulating EMT and cell migration. These observations
      have potential clinical relevance because the UBQLN1 gene is lost and
      underexpressed in a large percentage of human cancer cell lines, and primary
      human lung cancer samples and recurrent mutations in all five UBQLN family
      members have been identified in human lung cancers. Taken together, our results
      suggest for the first time a role for UBQLN family members in cancer biology.

PMID- 24747971
TI  - Cross talk between the bombesin neuropeptide receptor and Sonic hedgehog pathways
      in small cell lung carcinoma.
AB  - Small cell lung carcinoma (SCLC) often features the upregulation of the Sonic
      hedgehog (Shh) pathway leading to activation of Gli transcription factors. SCLC
      cells secrete bombesin (BBS)-like neuropeptides that act as autocrine growth
      factors. Here, we show that SCLC tumor samples feature co-expression of Shh and
      BBS-cognate receptor (gastrin-releasing peptide receptor (GRPR)). We also
      demonstrate that BBS activates Gli in SCLC cells, which is crucial for BBS
      mediated SCLC proliferation, because cyclopamine, an inhibitor of the Shh
      pathway, hampered the BBS-mediated effects. BBS binding to GRPR stimulated Gli
      through its downstream Galphaq and Galpha12/13 GTPases, and consistently, other
      Galphaq and Galpha13 coupled receptors (such as muscarinic receptor, m1, and
      thrombin receptor, PAR-1) and constitutively active GalphaqQL and Galpha12/13QL
      mutants stimulated Gli. By using cells null for Galphaq and Galpha12/13, we
      demonstrate that these G proteins are strictly necessary for Gli activation by
      BBS. Moreover, by using constitutively active Rho small G-protein (Rho QL) as
      well as its inhibitor, C3 toxin, we show that Rho mediates G-protein-coupled
      receptor (GPCR)-, Galphaq- and Galpha12/13-dependent Gli stimulation. At the
      molecular level, BBS caused a significant increase in Shh gene transcription and
      protein secretion that was dependent on BBS-induced GPCR/Galphaq-12/13/Rho
      mediated activation of nuclear factor kappaB (NFkappaB), which can stimulate a NF
      kappaB response element in the Shh gene promoter. Our data identify a novel
      molecular network acting in SCLC linking autocrine BBS and Shh circuitries and
      suggest Shh inhibitors as novel therapeutic strategies against this aggressive
      cancer type.

PMID- 24747972
TI  - Evi1 defines leukemia-initiating capacity and tyrosine kinase inhibitor
      resistance in chronic myeloid leukemia.
AB  - Relapse of chronic myeloid leukemia (CML) is triggered by stem cells with a
      reconstituting capacity similar to that of hematopoietic stem cells (HSCs) and
      CML stem cells are a source of resistance in drug therapy with tyrosine kinase
      inhibitors (TKIs). Ecotropic viral integration site 1 (EVI1), a key transcription
      factor in HSC regulation, is known to predict poor outcomes in myeloid
      malignancies, however, incapability of prospective isolation of EVI1-high
      leukemic cells precludes the functional evaluation of intraindividual EVI1-high
      cells. Introduction of CML into Evi1-internal ribosomal entry site (IRES)-green
      fluorescent protein (GFP) knock-in mice, a versatile HSC-reporter strain, enables
      us to separate Evi1-high CML cells from the individual. Evi1-IRES-GFP allele
      models of CML in chronic phase (CML-CP), by retroviral overexpression of BCR-ABL
      and by crossing BCR-ABL transgenic mice, revealed that Evi1 is predominantly
      enriched in the stem cell fraction and associated with an enhanced proliferative
      as well as a leukemia-initiating capacity and that Evi1-high CML-CP cells exhibit
      resistance to TKIs. Overexpressing BCR-ABL and NUP98-HOXA9 in Evi1-IRES-GFP knock
      in mice to model CML in blast crisis (CML-BC), in which Evi1-high cells turned to
      be a major population as opposed to a minor population in CML-CP models, showed
      that Evi1-high CML-BC cells have a greater potential to recapitulate the disease
      and appear resistant to TKIs. Furthermore, given that Evi1 heterozygosity
      ameliorates CML-CP and CML-BC development and that the combination of Evi1 and
      BCR-ABL causes acute myeloid leukemia resembling CML-BC, Evi1 could regulate CML
      development as a potent driver. In addition, in human CML-CP cases, we show that
      EVI1 is highly expressed in stem cell-enriched CD34+CD38-CD90+ fraction at single
      cell level. This is the first report to clarify directly that Evi1-high leukemic
      cells themselves possess the superior potential to Evi1-low cells in oncogenic
      self-renewal, which highlights the role of Evi1 as a valuable and a functional
      marker of CML stem cells.

PMID- 24747973
TI  - Orthotopic models of pediatric brain tumors in zebrafish.
AB  - High-throughput screens (HTS) of compound toxicity against cancer cells can
      identify thousands of potential new drug-leads. But only limited numbers of these
      compounds can progress to expensive and labor-intensive efficacy studies in mice,
      creating a 'bottle neck' in the drug development pipeline. Approaches that triage
      drug-leads for further study are greatly needed. Here we provide an intermediary
      platform between HTS and mice by adapting mouse models of pediatric brain tumors
      to grow as orthotopic xenografts in the brains of zebrafish. Freshly isolated
      mouse ependymoma, glioma and choroid plexus carcinoma cells expressing red
      fluorescence protein were conditioned to grow at 34  degrees C. Conditioned tumor
      cells were then transplanted orthotopically into the brains of zebrafish
      acclimatized to ambient temperatures of 34  degrees C. Live in vivo fluorescence
      imaging identified robust, quantifiable and reproducible brain tumor growth as
      well as spinal metastasis in zebrafish. All tumor xenografts in zebrafish
      retained the histological characteristics of the corresponding parent mouse tumor
      and efficiently recruited fish endothelial cells to form a tumor vasculature.
      Finally, by treating zebrafish harboring ERBB2-driven gliomas with an appropriate
      cytotoxic chemotherapy (5-fluorouracil) or tyrosine kinase inhibitor (erlotinib),
      we show that these models can effectively assess drug efficacy. Our data
      demonstrate, for the first time, that mouse brain tumors can grow orthotopically
      in fish and serve as a platform to study drug efficacy. As large cohorts of brain
      tumor-bearing zebrafish can be generated rapidly and inexpensively, these models
      may serve as a powerful tool to triage drug-leads from HTS for formal efficacy
      testing in mice. 

PMID- 24747974
TI  - Targeting NAD+ metabolism in the human malaria parasite Plasmodium falciparum.
AB  - Nicotinamide adenine dinucleotide (NAD+) is an essential metabolite utilized as a
      redox cofactor and enzyme substrate in numerous cellular processes. Elevated NAD+
      levels have been observed in red blood cells infected with the malaria parasite
      Plasmodium falciparum, but little is known regarding how the parasite generates
      NAD+. Here, we employed a mass spectrometry-based metabolomic approach to confirm
      that P. falciparum lacks the ability to synthesize NAD+ de novo and is reliant on
      the uptake of exogenous niacin. We characterized several enzymes in the NAD+
      pathway and demonstrate cytoplasmic localization for all except the parasite
      nicotinamidase, which concentrates in the nucleus. One of these enzymes, the P.
      falciparum nicotinate mononucleotide adenylyltransferase (PfNMNAT), is essential
      for NAD+ metabolism and is highly diverged from the human homolog, but
      genetically similar to bacterial NMNATs. Our results demonstrate the enzymatic
      activity of PfNMNAT in vitro and demonstrate its ability to genetically
      complement the closely related Escherichia coli NMNAT. Due to the similarity of
      PfNMNAT to the bacterial enzyme, we tested a panel of previously identified
      bacterial NMNAT inhibitors and synthesized and screened twenty new derivatives,
      which demonstrate a range of potency against live parasite culture. These results
      highlight the importance of the parasite NAD+ metabolic pathway and provide both
      novel therapeutic targets and promising lead antimalarial compounds. 

PMID- 24747976
TI  - Humanized mouse model to study bacterial infections targeting the
      microvasculature.
AB  - Neisseria meningitidis causes a severe, frequently fatal sepsis when it enters
      the human blood stream. Infection leads to extensive damage of the blood vessels
      resulting in vascular leak, the development of purpuric rashes and eventual
      tissue necrosis. Studying the pathogenesis of this infection was previously
      limited by the human specificity of the bacteria, which makes in vivo models
      difficult. In this protocol, we describe a humanized model for this infection in
      which human skin, containing dermal microvessels, is grafted onto
      immunocompromised mice. These vessels anastomose with the mouse circulation while
      maintaining their human characteristics. Once introduced into this model, N.
      meningitidis adhere exclusively to the human vessels, resulting in extensive
      vascular damage, inflammation and in some cases the development of purpuric rash.
      This protocol describes the grafting, infection and evaluation steps of this
      model in the context of N. meningitidis infection. The technique may be applied
      to numerous human specific pathogens that infect the blood stream. 

PMID- 24747975
TI  - Evaluating the association between p53 codon 72 Arg>pro polymorphism and risk of
      ovary cancer: a meta-analysis.
AB  - AIM: Allelic polymorphism in codon 72 of the p53 tumor suppressor gene causes
      imbalance of p53 protein expression. Earlier studies have shown association
      between allelic polymorphism in codon 72 of the p53 gene with risk of ovary
      cancer (OC); however the results are inconclusive and conflicting. Therefore, we
      performed this meta-analysis to investigate the relation between p53 codon 72
      Arg>Pro polymorphism and overall OC susceptibility. METHODS: We searched all
      eligible published studies based on the association between codon 72 of the p53
      Arg>Pro polymorphism and risk of OC. Data were pooled together from individual
      studies and meta-analysis was performed. Pooled odds ratios (ORs) and 95% CI were
      calculated for allele contrast, homozygous, heterozygous, dominant and recessive
      genetic models. RESULTS: A total of twelve studies comprising of 993 OC cases and
      1264 healthy controls were included in this meta-analysis. Overall, no
      significant association was detected for Pro allele carrier (Pro vs. Arg: p =
      0.916; OR = 0.980, 95% CI = 0.677 to 1.419), homozygous (Pro/Pro vs. Arg/Arg: p =
      0.419; OR = 0.731, 95% CI = 0.341 to 1.564), heterozygous (Arg/Pro vs. Arg/Arg: p
      = 0.248; OR = 1.237, 95% CI = 0.862 to 1.773), dominant (Pro/Pro+Arg/Pro
      vsArg/Arg: p = 0.699; OR = 1.089, 95% CI = 0.706 to 1.681), and recessive
      (Pro/Pro vs Arg/Arg+Arg/Pro: p = 0.329; OR = 0.754, 95% CI = 0.428 to 1.329)
      genetic models, respectively. Also, in the stratified analysis by ethnicity, no
      significant association of this polymorphism with risk of OC was found in the
      Caucasian population. CONCLUSIONS: This meta-analysis suggested that codon 72 of
      the p53 Arg>Pro polymorphism may not significantly contribute in ovary cancer
      susceptibility. However, future large studies with gene-gene and gene-environment
      interactions are needed to validate these findings.

PMID- 24747977
TI  - The asparaginyl endopeptidase legumain is essential for functional recovery after
      spinal cord injury in adult zebrafish.
AB  - Unlike mammals, adult zebrafish are capable of regenerating severed axons and
      regaining locomotor function after spinal cord injury. A key factor for this
      regenerative capacity is the innate ability of neurons to re-express growth
      associated genes and regrow their axons after injury in a permissive environment.
      By microarray analysis, we have previously shown that the expression of legumain
      (also known as asparaginyl endopeptidase) is upregulated after complete
      transection of the spinal cord. In situ hybridization showed upregulation of
      legumain expression in neurons of regenerative nuclei during the phase of axon
      regrowth/sprouting after spinal cord injury. Upregulation of Legumain protein
      expression was confirmed by immunohistochemistry. Interestingly, upregulation of
      legumain expression was also observed in macrophages/microglia and neurons in the
      spinal cord caudal to the lesion site after injury. The role of legumain in
      locomotor function after spinal cord injury was tested by reducing Legumain
      expression by application of anti-sense morpholino oligonucleotides. Using two
      independent anti-sense morpholinos, locomotor recovery and axonal regrowth were
      impaired when compared with a standard control morpholino. We conclude that
      upregulation of legumain expression after spinal cord injury in the adult
      zebrafish is an essential component of the capacity of injured neurons to regrow
      their axons. Another feature contributing to functional recovery implicates
      upregulation of legumain expression in the spinal cord caudal to the injury site.
      In conclusion, we established for the first time a function for an unusual
      protease, the asparaginyl endopeptidase, in the nervous system. This study is
      also the first to demonstrate the importance of legumain for repair of an injured
      adult central nervous system of a spontaneously regenerating vertebrate and is
      expected to yield insights into its potential in nervous system regeneration in
      mammals. 

PMID- 24747978
TI  - The effects of quetiapine on sleep in recovering alcohol-dependent subjects: a
      pilot study.
AB  - OBJECTIVE: The aim of this hypothesis-generating pilot study was to assess
      prospectively the objective and subjective effects of treatment with quetiapine
      XR on sleep during early recovery from alcohol dependence (AD). METHODS:
      Recovering subjects with AD and sleep disturbance complaints were treated with
      quetiapine XR (n = 10) or matching placebo pills (n = 10) for 8 weeks.
      Polysomnography was used to assess sleep objectively, and the Insomnia Severity
      Index and Pittsburgh Sleep Quality Index were used to measure subjective
      insomnia. Other assessment measures included the 10-minute psychomotor vigilance
      task (for neurobehavioral functioning), the time-line follow-back measure (for
      alcohol consumption), the Penn Alcohol Craving Scale (for alcohol craving), the
      Patient Health Questionnaire-9 item scale (for depressive symptoms), and the Beck
      Anxiety Inventory (for anxiety symptoms). RESULTS: Although there was no effect
      of quetiapine XR on sleep efficiency (time spent asleep/total recording time),
      there was a pre-to-post reduction in wake after sleep onset time (P = 0.03) and
      nonsignificant trends for increases in sleep onset latency (SOL) and stage 2
      sleep time. A time * drug interaction was seen for the subjective insomnia, such
      that quetiapine XR-treated subjects reported greater initial improvement in their
      subjective insomnia, but the difference was not sustained. There were no
      differences between treatment groups on other measures or medication compliance.
      CONCLUSION: Quetiapine XR improves objective sleep continuity and transiently
      improves subjective insomnia early in recovery from AD.

PMID- 24747979
TI  - Therapeutic satisfaction and subjective effects of different strains of
      pharmaceutical-grade cannabis.
AB  - In The Netherlands, pharmaceutical-grade cultivated cannabis is distributed for
      medicinal purposes as commissioned by the Ministry of Health. Few studies have
      thus far described its therapeutic efficacy or subjective (adverse) effects in
      patients. The aims of this study are to assess the therapeutic satisfaction
      within a group of patients using prescribed pharmaceutical-grade cannabis and to
      compare the subjective effects among the available strains with special focus on
      their delta-9-tetrahydrocannabinol and cannabidiol content. In a cross-sectional
      and natural design, users of pharmaceutical-grade cannabis were investigated with
      questionnaires. Medical background of the patients was asked as well as
      experienced therapeutic effects and characteristics of cannabis use. Subjective
      effects were measured with psychometric scales and used to compare among the
      strains of cannabis used across this group of patients. One hundred two patients
      were included; their average age was 53 years and 76% used it for more than a
      year preceding this study. Chronic pain (53%; n = 54) was the most common medical
      indication for using cannabis followed by multiple sclerosis (23%; n = 23), and
      86% (n = 88) of patients (almost) always experienced therapeutic satisfaction
      when using pharmaceutical cannabis. Dejection, anxiety, and appetite stimulation
      were found to differ among the 3 strains of cannabis. These results show that
      patients report therapeutic satisfaction with pharmaceutical cannabis, mainly
      pain alleviation. Some subjective effects were found to differ among the
      available strains of cannabis, which is discussed in relation to their different
      tetrahydrocannabinol/cannabidiol content. These results may aid in further
      research and critical appraisal for medicinally prescribed cannabis products. 

PMID- 24747981
TI  - Obtaining patient feedback in an outpatient lithotripsy service is facilitated by
      use of a touch-screen tablet (iPadTM) survey.
AB  - There is now a requirement for every doctor in the UK to obtain patient feedback
      for revalidation. This can be an onerous and time-consuming task. The objective
      of this study was to evaluate a novel electronic patient feedback method in an
      outpatient lithotripsy service setting. Between September 2013 and January 2014,
      100 patients attending an outpatient lithotripsy service in Oxford were asked to
      complete a selection of pre-approved NHS questions about the service they had
      received. Questions were presented on a tablet device (iPadTM) and answered using
      the touch screen. Departmental staff were unaware of the questions in the survey.
      Patients were asked to complete the survey by an independent research nurse.
      Questions were created online in a free-to-use web-based survey application and
      presented on the tablet device in a user-friendly format via an application. Data
      were uploaded via wifiTM to the online system. Data were viewed, automatically
      analysed and displayed graphically. The age range of the patients surveyed was 20
      80 years of age. All 100 patients completed the survey without difficulty. All
      patients answered every question. Data could be automatically viewed, analysed
      and presented graphically. This method of collecting patient feedback proved to
      be rapid and efficient. The feedback highlighted a high patient satisfaction with
      the lithotripsy service. A touch screen tablet device is an efficient and
      effective method of collecting truly objective patient feedback. This method of
      patient feedback could be employed in other clinical environments to collect data
      for revalidation purposes.

PMID- 24747980
TI  - Benzo[a]pyrene effects on reproductive endpoints in Fundulus heteroclitus.
AB  - Benzo[a]pyrene (BaP) is a polycyclic aromatic hydrocarbon (PAH) that has been
      implicated in modulating aromatase enzyme function with the potential to
      interrupt normal reproductive function. The aim of this study was to use a fish
      model, Fundulus heteroclitus, to assess whether BaP exposure adversely impacts
      reproduction. Adult fish were exposed to waterborne BaP nominal concentrations of
      (0, 1, or 10 MUg/l) for 28 days. Males and females were combined for the second
      half of the exposure (days 14-28) in order to quantitate egg production and
      fertilization success. Egg fertilization and subsequent hatching success of F1
      embryos was significantly decreased by the high dose of BaP. In males, both gonad
      weight and plasma testosterone concentrations were significantly reduced compared
      to controls by 10 MUg/l BaP. Histopathological examination of testes including
      spermatogonia, spermatocyte and spermatid cyst areas, percentage of cysts per
      phase, and area of spermatozoa per seminiferous tubule were not significantly
      affected. Other biomarkers, including male liver weight, liver vitellogenin (vtg)
      mRNA expression and sperm concentrations, were also not affected. In females,
      estradiol concentrations were significantly reduced after BaP exposure, but egg
      production, gonad weight, liver weight, vtg expression and oocyte maturation were
      not altered. Steroid concentrations in Fundulus larvae from exposed parents at 1
      and 3 weeks posthatch were not significantly changed. BaP exposure at these
      environmentally relevant concentrations caused negative alterations particularly
      in male fish to both biochemical and phenotypic biomarkers associated with
      reproduction and multigenerational embryo survival. 

PMID- 24747982
TI  - Phthalic acid esters in soils from vegetable greenhouses in Shandong Peninsula,
      East China.
AB  - Soils at depths of 0 cm to 10 cm, 10 cm to 20 cm, and 20 cm to 40 cm from 37
      vegetable greenhouses in Shandong Peninsula, East China, were collected, and 16
      phthalic acid esters (PAEs) were detected using gas chromatography-mass
      spectrometry (GC-MS). All 16 PAEs could be detected in soils from vegetable
      greenhouses. The total of 16 PAEs (Sigma16PAEs) ranged from 1.939 mg/kg to 35.442
      mg/kg, with an average of 6.748 mg/kg. Among four areas, including Qingdao,
      Weihai, Weifang, and Yantai, the average and maximum concentrations of
      Sigma16PAEs in soils at depths of 0 cm to 10 cm appeared in Weifang, which has a
      long history of vegetable production and is famous for extensive greenhouse
      cultivation. Despite the different concentrations of Sigma16PAEs, the PAE
      compositions were comparable. Among the 16 PAEs, di(2-ethylhexyl) phthalate
      (DEHP), di-n-octyl phthalate (DnOP), di-n-butyl phthalate (DnBP), and diisobutyl
      phthalate (DiBP) were the most abundant. Compared with the results on
      agricultural soils in China, soils that are being used or were used for vegetable
      greenhouses had higher PAE concentrations. Among PAEs, dimethyl phthalate (DMP),
      diethyl phthalate (DEP) and DnBP exceeded soil allowable concentrations (in US)
      in more than 90% of the samples, and DnOP in more than 20%. Shandong Peninsula
      has the highest PAE contents, which suggests that this area is severely
      contaminated by PAEs. 

PMID- 24747983
TI  - Examination of synaptic vesicle recycling using FM dyes during evoked,
      spontaneous, and miniature synaptic activities.
AB  - Synaptic vesicles in functional nerve terminals undergo exocytosis and
      endocytosis. This synaptic vesicle recycling can be effectively analyzed using
      styryl FM dyes, which reveal membrane turnover. Conventional protocols for the
      use of FM dyes were designed for analyzing neurons following stimulated (evoked)
      synaptic activity. Recently, protocols have become available for analyzing the FM
      signals that accompany weaker synaptic activities, such as spontaneous or
      miniature synaptic events. Analysis of these small changes in FM signals requires
      that the imaging system is sufficiently sensitive to detect small changes in
      intensity, yet that artifactual changes of large amplitude are suppressed. Here
      we describe a protocol that can be applied to evoked, spontaneous, and miniature
      synaptic activities, and use cultured hippocampal neurons as an example. This
      protocol also incorporates a means of assessing the rate of photobleaching of FM
      dyes, as this is a significant source of artifacts when imaging small changes in
      intensity. 

PMID- 24747984
TI  - Growth inhibitory, bactericidal, and morphostructural effects of dehydrocostus
      lactone from Magnolia sieboldii Leaves on antibiotic-susceptible and -resistant
      strains of Helicobacter pylori.
AB  - Helicobacter pylori is associated with various diseases of the upper
      gastrointestinal tract, such as gastric inflammation and duodenal and gastric
      ulcers. The aim of the study was to assess anti-H. pylori effects of the
      sesquiterpene lactone dehydrocostus lactone (DCL) from Magnolia sieboldii leaves,
      compared to commercial pure DCL, two previously known sesquiterpene lactones
      (costunolide and parthenolide), (-)-epigallocatechin gallate, and four
      antibiotics. The antibacterial activity of natural DCL toward antibiotic
      susceptible H. pylori ATCC 700392 and H. pylori ATCC 700824 strains (MIC, 4.9 and
      4.4 mg/L) was similar to that of commercial DCL and was more effective than
      costunolide, parthenolide, and EGCG. The activity of DCL was slightly lower than
      that of metronidazole (MIC, 1.10 and 1.07 mg/L). The antibacterial activity of
      DCL was virtually identical toward susceptible and resistant strains, even though
      resistance to amoxicillin (MIC, 11.1 mg/L for PED 503G strain), clarithromycin
      (49.8 mg/L for PED 3582GA strain), metronidazole (21.6 mg/L for H. pylori ATCC
      43504 strain; 71.1 mg/L for 221 strain), or tetracycline (14.2 mg/L for B strain)
      was observed. This finding indicates that DCL and the antibiotics do not share a
      common mode of action. The bactericidal activity of DCL toward H. pylori ATCC
      43504 was not affected by pH values examined (4.0-7.0). DCL caused considerable
      conversion to coccoid form (94 versus 49% at 8 and 4 mg/L of DCL for 48 h). The
      Western blot analysis revealed that urease subunits (UreA and UreB) of H. pylori
      ATCC 43504 were not affected by 10 mM of DCL, whereas UreA monomer band
      completely disappeared at 0.1 mM of (-)-epigallocatechin gallate. Global efforts
      to reduce the level of antibiotics justify further studies on M. sieboldii leaf
      derived materials containing DCL as potential antibacterial products or a lead
      molecule for the prevention or eradication of drug-resistant H. pylori. 

PMID- 24747985
TI  - Expression of the ABC transport proteins MDR1 (ABCB1) and BCRP (ABCG2) in bovine
      rumen.
AB  - Rumen fermentation of plant-based forage in bovines is the major site for
      generation and absorption of short-chain fatty acids. Consequentially, the rumen
      is also the site for initial exposure to toxins released from diet. Accordingly,
      we have investigated the expression of bovine ABC transporters in the rumen
      associated with cytoprotection against xenobiotic exposure, namely MDR1 (ABCB1),
      MRP2 (ABCC2) and BCRP (ABCG2). Bovine rumen samples from the ventral sac were
      obtained post-mortem from a commercial slaughterhouse after humane killing. Rumen
      papilla samples were then prepared for total RNA isolation for RT-PCR, SDS
      PAGE/Western blotting and immunohistochemistry. PCR products of the predicted
      size were observed for both MDR1 and BCRP, but not for MRP2 using bovine-specific
      primers. beta-actin was used as a control transcript. Western blot analysis using
      C219 primary monoclonal antibody revealed MDR1 protein expression in bovine rumen
      (Mapp, of ~170-180 kD). Immunolocalisation of MDR1 using UIC2 monoclonal antibody
      within cryosections of bovine rumen showed extensive membrane staining in the
      cells of the stratum granulosum, stratum spinosum and stratum basale. MDR1
      expression was absent from outer stratum corneum. Protein expression and
      immunolocalisation were also confirmed for BCRP, with prevalent staining in the
      stratum basale, becoming weaker in the stratum spinosum and stratum granulosum. 

PMID- 24747987
TI  - Transcriptome analysis of the gill of Takifugu rubripes using Illumina sequencing
      for discovery of SNPs.
AB  - Single nucleotide polymorphisms (SNPs) have become the marker of choice for
      genome-wide association studies in many species. High-throughput sequencing of
      RNA was developed primarily to analyze global gene expression, while it is an
      efficient way to discover SNPs from the expressed genes. In this study, we
      conducted transcriptome sequencing of the gill samples of Takifugu rubripes
      analyzed by using Illumina HiSeq 2000 platform to identify gene-associated SNPs
      from the transcriptome of T. rubripes gill. A total of 27,085,235 unique-mapped
      reads from 55,061,524 raw data reads were generated. A total of 56,972 putative
      SNPs were discovered, which were located in 11,327 genes. 35,839 SNPs were
      transitions (Ts), 21,074 SNPs were transversions (Tv) and 88.1% of 56,972 SNPs
      were assigned to the 22 chromosomes. The average minor allele frequency (MAF) of
      the SNPs was 0.26. GO and KEGG pathway analyses were conducted to analyze the
      genes containing SNPs. Validation of selected SNPs revealed that 63.4% of SNPs
      (34/52) were true SNPs. RNA-Seq is a cost-effective way to discover gene
      associated SNPs. In this study, a large number of SNPs were identified and these
      data will be useful resources for population genetic study, evolution analysis,
      resource assessment, genetic linkage analysis and genome-wide association
      studies. The results of our study can also offer some useful information as
      molecular makers to help select and cultivate T. rubripes. 

PMID- 24747988
TI  - Outcomes and predictive factors of prostate cancer patients with extremely high
      prostate-specific antigen level.
AB  - PURPOSE: Prostate-specific antigen (PSA) is a useful biomarker of prostate cancer
      (PCa). High-risk localized PCa is defined using T stage, Gleason score (GS), and
      PSA. However, PSA level defining high-risk PCa is at most 20 ng/mL. In PCa
      patients with high PSA, it is unclear whether PSA itself can be a prognostic
      factor. METHODS: Of 642 patients who were diagnosed as PCa, 90 patients with PSA
      > 100 ng/mL were retrospectively analyzed. Patients were divided into three
      groups according to PSA level: very high (>1,000 ng/mL), moderately high (200
      1,000 ng/mL), and slightly high (100-200 ng/mL). RESULTS: There were no
      significant differences in overall survival or PCa-specific survival (PCaSS)
      among the three groups. Regardless of PSA level, high M stage and GS
      significantly reduced PCaSS. When the risk classification was made using M stage
      and GS (high risk = M1 and GS >= 9, low risk = M0 and GS < 9, and intermediate
      risk = others), PCaSS was significantly different among high-, intermediate-, and
      low-risk groups with 5-year survival rates of 58.2, 80.6, and 100 %,
      respectively. Although there were no differences in treatment performed during
      the castration-resistant stage, patients undergoing alternative anti-androgen and
      zoledronic acid treatment had better PCaSS after being castration-resistant.
      CONCLUSIONS: As PSA could not be a prognostic factor in PCa patients with high
      PSA > 100 ng/mL, the novel risk classification using M stage and GS may help
      clinicians to predict PCaSS and to plan follow-up schedules after diagnosis.

PMID- 24747989
TI  - Thermopressurized diluted phosphoric acid pretreatment of ligno(hemi)cellulose to
      make free sugars and nutraceutical oligosaccharides.
AB  - Ligno(hemi)cellulosics (L(h)Cs) as sugarcane bagasse and loblolly pine sawdust
      are currently being used to produce biofuels such as bioethanol and biobutanol
      through fermentation of free sugars that are often obtained enzymatically.
      However, this bioconversion requires a pretreatment to solubilize the
      hemicellulose fractions, thus facilitating the action of the cellulolytic
      enzymes. Instead of the main free monosaccharides used in these current models,
      the modulation of thermopressurized orthophosphoric acid as a pretreatment, in
      the ranges of 3-12 atm and pH 1.5-2.5, can produce nondigestible oligosaccharides
      (NDOS) such as xylo-oligosaccharides (XOS) because heteroxylan is present in both
      types of hardwood and softwood hemicelluloses. A comparative thin-layer
      chromatographic analysis of the hydrolytic products showed the best conditions
      for NDOS production to be 7 atm/water, pH 2.25 and 2.50, and 8.5 atm/water for
      both sources. Particular hydrolysates from 7 atm (171  degrees C) at pHs 2.25 and
      2.50 both for cane bagasse and pine sawdust, with respective oligosaccharide
      contents of 57 and 59 %, once mixed in a proportion of 1:1 for each plant source,
      were used in vitro as carbon sources for Bifidobacterium or Lactobacillus. Once
      both bacteria attained the stationary phase of growth, an unforeseen feature
      emerged: the preference of B. animalis for bagasse hydrolysates and, conversely,
      the preference of L. casei for pine hydrolysates. Considering the fact that
      nutraceutical oligosaccharides from both hemicelluloses correspond to higher
      value-added byproducts, the technology using a much diluted thermopressurized
      orthophosphoric acid pretreatment becomes an attractive choice for L(h)Cs.

PMID- 24747990
TI  - Hot biological catalysis: isothermal titration calorimetry to characterize
      enzymatic reactions.
AB  - Isothermal titration calorimetry (ITC) is a well-described technique that
      measures the heat released or absorbed during a chemical reaction, using it as an
      intrinsic probe to characterize virtually every chemical process. Nowadays, this
      technique is extensively applied to determine thermodynamic parameters of
      biomolecular binding equilibria. In addition, ITC has been demonstrated to be
      able of directly measuring kinetics and thermodynamic parameters (kcat, KM,
      DeltaH) of enzymatic reactions, even though this application is still
      underexploited. As heat changes spontaneously occur during enzymatic catalysis,
      ITC does not require any modification or labeling of the system under analysis
      and can be performed in solution. Moreover, the method needs little amount of
      material. These properties make ITC an invaluable, powerful and unique tool to
      study enzyme kinetics in several applications, such as, for example, drug
      discovery. In this work an experimental ITC-based method to quantify kinetics and
      thermodynamics of enzymatic reactions is thoroughly described. This method is
      applied to determine kcat and KM of the enzymatic hydrolysis of urea by Canavalia
      ensiformis (jack bean) urease. Calculation of intrinsic molar enthalpy
      (DeltaHint) of the reaction is performed. The values thus obtained are consistent
      with previous data reported in literature, demonstrating the reliability of the
      methodology. 

PMID- 24747991
TI  - Reactive oxygen species regulate the quiescence of CD34-positive cells derived
      from human embryonic stem cells.
AB  - AIMS: Reactive oxygen species (ROS) are involved in a wide range of cellular
      processes. However, few studies have examined the generation and function of ROS
      in human embryonic vascular development. In this study, the sources of ROS and
      their roles in the vascular differentiation of human embryonic stem cells (hESCs)
      were investigated. METHODS AND RESULTS: During vascular differentiation of hESCs,
      CD34(+) cells had quiescence-related gene expression profiles and a large
      fraction of these cells were in G0 phase. In addition, levels of ROS, which were
      primarily generated through NOX4, were substantially higher in hESC-derived
      CD34(+) cells than in hESC-derived CD34(-) cells. To determine whether excess
      levels of ROS induce quiescence of hESC-derived CD34(+) cells, ROS levels were
      moderately reduced using selenium to enhance antioxidant activities of
      thioredoxin reductase and glutathione peroxidase. In comparison to untreated
      CD34(+) cells, selenium-treated CD34(+) cells exhibited changes in gene
      expression that favoured cell cycle progression, and had a greater proliferation
      and a smaller fraction of cells in G0 phase. Thus, selenium treatment increased
      the number of hESC-derived CD34(+) cells, thereby enhancing the efficiency with
      which hESCs differentiated into vascular endothelial and smooth muscle cells.
      CONCLUSION: This study reveals that NOX4 produces ROS in CD34(+) cells during
      vascular differentiation of hESCs, and shows that modulation of ROS levels using
      antioxidants such as selenium may be a novel approach to increase the vascular
      differentiation efficiency of hESCs.

PMID- 24747992
TI  - Jumping to Conclusions bias, BADE and Feedback Sensitivity in schizophrenia and
      schizotypy.
AB  - Several studies about schizophrenia have shown a cognitive bias named "Jumping to
      Conclusions" (JTC), defined as a decision made quickly on the basis of little
      evidence that occurs in these patients when performing probabilistic reasoning
      paradigms. The main objective of this study is to compare JTC bias and BADE (Bias
      Against Disconfirmatory Evidence) in patients with schizophrenia vs. participants
      with high/low schizotypy to understand the underlying mechanism of these
      cognitive biases. Probabilistic reasoning was assessed using a modified version
      of Drawing to Decision task. In addition to the traditional parameters of this
      task (Plausibility Rating (PR), Draws to Decision (DTD), BADE) we also calculated
      new parameters, overall accuracy and one named Feedback Sensitivity (FS) which
      lower scores shows greater use of feedback. The results of the study suggest a
      context effect: in the cued condition, there were not main differences between
      groups. In the uncued condition, we found higher JTC bias at stage 1 for
      patients. At the same time, PR at first stages related positively with Feedback
      Sensitivity and negatively with accuracy for patients and high schizotypy
      participants (high confidence is associated with worse performance and lower
      feedback use). BADE seems unrelated to JTC bias and FS. The results are discussed
      in terms of JTC like as a clinical bias and whether patients with schizophrenia
      are less able to use feedback. 

PMID- 24747986
TI  - Amoebal endosymbiont Neochlamydia genome sequence illuminates the bacterial role
      in the defense of the host amoebae against Legionella pneumophila.
AB  - Previous work has shown that the obligate intracellular amoebal endosymbiont
      Neochlamydia S13, an environmental chlamydia strain, has an amoebal infection
      rate of 100%, but does not cause amoebal lysis and lacks transferability to other
      host amoebae. The underlying mechanism for these observations remains unknown. In
      this study, we found that the host amoeba could completely evade Legionella
      infection. The draft genome sequence of Neochlamydia S13 revealed several defects
      in essential metabolic pathways, as well as unique molecules with leucine-rich
      repeats (LRRs) and ankyrin domains, responsible for protein-protein interaction.
      Neochlamydia S13 lacked an intact tricarboxylic acid cycle and had an incomplete
      respiratory chain. ADP/ATP translocases, ATP-binding cassette transporters, and
      secretion systems (types II and III) were well conserved, but no type IV
      secretion system was found. The number of outer membrane proteins (OmcB, PomS, 76
      kDa protein, and OmpW) was limited. Interestingly, genes predicting unique
      proteins with LRRs (30 genes) or ankyrin domains (one gene) were identified.
      Furthermore, 33 transposases were found, possibly explaining the drastic genome
      modification. Taken together, the genomic features of Neochlamydia S13 explain
      the intimate interaction with the host amoeba to compensate for bacterial
      metabolic defects, and illuminate the role of the endosymbiont in the defense of
      the host amoebae against Legionella infection. 

PMID- 24747993
TI  - Implicit visual learning: how the task set modulates learning by determining the
      stimulus-response binding.
AB  - Implicit learning is one of the most fundamental learning mechanisms that enables
      humans to adapt to regularities inherent in the environment. Despite its high
      flexibility, it depends on constraints, such as selective attention. Here, we
      focused on the stimulus-to-response binding which defines the dimensions of the
      stimuli and the responses participants attend to. In a serial reaction time task
      with a visual sequence, we investigated whether this stimulus-response binding
      influences the amount of sequence learning. The results of Experiments 1 and 2
      showed that visual sequence learning is reduced when participants do not attend
      to the relevant response dimension. Furthermore, the findings of Experiment 3
      suggest that attention to the relevant response dimension increased the
      development of explicit knowledge without affecting implicit knowledge. This
      latter finding is difficult to reconcile with the assumption that explicit
      learning results from the gradual strengthening of sequence representations. 

PMID- 24747994
TI  - Diabetes, incretin hormones and cardioprotection.

PMID- 24747995
TI  - The safety of high-field MRI?

PMID- 24747996
TI  - The effect of three ergonomics training programs on the prevalence of low-back
      pain among workers of an Iranian automobile factory: a randomized clinical trial.
AB  - BACKGROUND: Many workers suffer from low-back pain. Type and severity of spinal
      complaints have relationship with work load. Lack of adherence to ergonomics
      recommendations among the important causes of low-back pain. OBJECTIVE: To assess
      the effect of 3 ergonomics training programs on the prevalence of lowback pain
      among workers of an Iranian automobile factory. METHODS: In a parallel-design 4
      arm randomized clinical trial, 760 active workers of an automobile factory were
      studied. 503 workers were found eligible and randomized into 3 intervention
      groups (n=252), and a control group (n=251). The intervention groups consisted of
      3 arms: 84 workers were educated by pamphlet, 84 by lectures, and 84 by workshop.
      Nordic questionnaire was used to determine the prevalence of spinal complaint
      before and 1-year after the interventions. The trial is registered with the
      Iranian Randomized Clinical Trial Registry, number IRCT2013061213182N2. RESULTS:
      Out of 503 workers, 52 lost to follow-up leaving 451 workers for analyses. The
      prevalence of low-back pain at the baseline was not significantly different among
      the studied arms. 1-year after the interventions, the prevalence did not change
      significantly from the baseline values for the lecture and pamphlet group.
      However, the prevalence of LBP experienced during the last year significantly
      (p=0.036) decreased from 42% to 23% in participant took part in the workshop.
      CONCLUSION: Training of automobile factory workers in ergonomics is more
      effective by running workshop than giving lecture or disseminating pamphlet.

PMID- 24747997
TI  - Does the perception of psychosocial factors increase the risk of pesticide
      exposure among seasonal Hispanic farmworkers?
AB  - BACKGROUND: Migrant farmworkers are prone to several psychosocial stressors.
      OBJECTIVE: To investigate the effect of perceived psychosocial factors on
      pesticide exposure among seasonal migrant Hispanic farmworkers in North Carolina,
      USA. METHODS: A cross-sectional interview survey of 187 seasonal migrant
      farmworkers of Mexican descent, identified from labor camps located in rural
      counties in North Carolina, was conducted using nonprobability purposive sampling
      approach. Multivariable ordinal logistic regression analysis was used to
      determine the relationship between perceived control over the harmful effects of
      pesticide exposure, lack of social support, and the impact of anxiety on
      perception of pesticide exposure. RESULTS: More than 20% (n=39) of farmworkers
      reported frequent or constant contact with pesticides while working in the
      fields. More than 68% of farmworkers reported they believe they have control over
      avoiding harmful effects of pesticide exposure; the odds of pesticide exposure
      were 55% lower in this group (adjusted OR: 0.45; 95% CI: 0.22-0.91). No
      significant relationship was observed between farmworkers perception of lack of
      social support and presence of anxiety with odds of on-field pesticide exposure.
      CONCLUSION: The study results suggest that perception of control is an important
      predictor of reduced pesticide exposure among seasonal migrant farmworkers.

PMID- 24747998
TI  - Psychomotor effects of mixed organic solvents on rubber workers.
AB  - BACKGROUND: Exposure to organic solvents is common among workers. OBJECTIVE: To
      assess neurobehavioral effects of long-term exposure to organic solvents among
      rubber workers in Tehran, Iran. METHODS: Across-sectional study was conducted on
      223 employees of a rubber industry. The participants completed a data collection
      sheet on their occupational and medical history, and demographic characteristics
      including age, work experience, education level; they performed 6 psychiatric
      tests on the neurobehavioral core test battery (NCTB) that measure simple
      reaction time, short-term memory (digit span, Benton), eye-hand coordination
      (Purdue pegboard, pursuit aiming), and perceptual speed (digit symbol). RESULTS:
      Workers exposed and not exposed to organic solvents had similar age and education
      distribution. The mean work experience of the exposed and non-exposed workers was
      5.9 and 4.4 years, respectively. The exposed workers had a lower performance
      compared to non-exposed workers in all psychomotor tests. After controlling for
      the confounders by logistic regression analysis, it was found that exposure to
      organic solvents had a significant effect on the results of digit symbols, digit
      span, Benton, aiming, and simple reaction time tests. No significant effect was
      observed in pegboard test. CONCLUSION: Occupational exposure to organic solvent
      can induce subtle neurobehavioral changes among workers exposed to organic
      solvents; therefore, periodical evaluation of the central nervous system by
      objective psychomotor tests is recommended among those who are chronically
      exposed to organic solvents.

PMID- 24747999
TI  - Determinants of occupational injury in Kombolcha textile factory, North-East
      Ethiopia.
AB  - BACKGROUND: Textile factory is among the most common manufacturing industries
      that has higher rate of work-related injuries. Knowing the associated factors of
      work-related injuries can be a critical step for improving the working condition
      of workers in the sector. OBJECTIVE: To assess the major determinants of
      occupational injury among workers in Kombolcha textile factory, North-East
      Ethiopia. METHODS: An institution-based cross-sectional study was conducted from
      April 1 to 15, 2013 on 455 randomly selected workers after stratification by
      working departments. The data was collected using a structured questionnaire
      through face-to-face interview by data collectors of 6 occupational health
      experts and 6 nurses. RESULTS: Working >48 hrs/wk (aOR: 2.71, 95% CI: 1.18-6.24),
      handling objects >20 kg (aOR: 2.35, 95% CI: 1.24-4.45), visual concentration
      (aOR: 3.10, 95% CI: 1.42-6.75), timely maintenance of machine (aOR: 1.80, 95% CI:
      1.11-2.93), and sleep disorder (aOR: 2.95, 95% CI: 1.47-5.92) were significant
      factors for the occurrence of occupational injuries. CONCLUSION: Many factors
      including working for a long time with accurate instruments and sleep disorders
      can cause occupational injury in textile industries.

PMID- 24748000
TI  - Prevalence and risk factors of hypertension among bank employees in urban
      Puducherry, India.
AB  - BACKGROUND: There is paucity of information on the prevalence of hypertension and
      its risk factors among bank employees at global level. OBJECTIVE: To assess the
      prevalence and risk factors of hypertension among bank employees in Puducherry,
      India. METHODS: A cross-sectional study was conducted on 192 (128 male and 64
      female) bank employees from 12 nationalized banks in urban Puducherry, India.
      Blood pressure was measured and classified according to the Joint National
      Committee (JNC) VII criteria. Data on risk factors of hypertension, including
      consumption of extra salt while dining, eating high-salt food, junk food,
      servings of fruits and vegetables, smoking, alcohol use, physical activity, and
      body mass index, were obtained for each participant using a standard
      questionnaire. Stress level was assessed by Cohen's Perceived Stress scale. Data
      was analyzed by Chi-square test and multiple logistic regression analysis.
      RESULTS: The mean+/-SD age of the participants was 39.5+/-10.6 years. The
      prevalence of hypertension and pre-hypertension was 44.3% (95% CI: 37.2%-51.3%)
      and 41.1% (95% CI: 34.1%-48.1%), respectively. Of 85 participants with
      hypertension, 47 (55%) was known case and 38 (45%) were newly diagnosed. Multiple
      logistic regression analysis revealed that living in the 4th (OR: 3.13) or 6th
      (OR: 3.11) decade of life, consumption of extra salt (OR: 2.49), and physical
      activity >=2 hours per day (OR: 0.21) were associated with hypertension among
      bank employees. CONCLUSION: Prevalence of hypertension is high among bank
      employees. There is a need for strengthening adoption of certain interventional
      measures in lifestyle such as reducing salt intake and promoting physical
      activity among this vulnerable group.

PMID- 24748001
TI  - High-field MRI and mercury release from dental amalgam fillings.
AB  - Mercury is among the most toxic nonradioactive elements which may cause toxicity
      even at low doses. Some studies showed release of mercury from dental amalgam
      fillings in individuals who used mobile phone. This study was conducted to assess
      the effect of high-field MRI on mercury release from dental amalgam filling. We
      studied two groups of students with identical tooth decays requiring a similar
      pattern of restorative dentistry. They were exposed to a magnetic flux density of
      1.5 T produced by a MRI machine. 16 otherwise healthy students with identical
      dental decay participated in this study. They underwent similar restorative
      dentistry procedures and randomly divided into two groups of MRI-exposed and
      control arms. Urinary concentrations of mercury in the control subjects were
      measured before (hour 0) and 48 and 72 hrs after amalgam restoration, using cold
      vapor atomic absorption spectrometry. Urinary concentrations of mercury in
      exposed individuals were determined before (hour 0), and 24, 48, 72 and 96 hrs
      after amalgam restoration. Unlike control subjects, they underwent conventional
      brain MRI (15 min, 99 slices), 24 hrs after amalgam restoration. The mean+/-SD
      urinary mercury levels in MRI-exposed individuals increased linearly from a
      baseline value of 20.70+/-17.96 to 24.83+/-22.91 MUg/L 72 hrs after MRI. In the
      control group, the concentration decreased linearly from 20.70+/-19.77 to 16.14+/
      20.05 MUg/L. The difference between urinary mercury in the exposed and control
      group, 72 hrs after MRI (96 h after restoration),was significant (p=0.046). These
      findings provide further support for the noxious effect of MRI (exposure to
      strong magnetic field)and release of mercury from dental amalgam fillings. 

PMID- 24748002
TI  - Acute inhalation exposure to titanium ethanolate as a possible cause of metal
      fume fever.
AB  - Occupational inhalation exposure to noxious agents is not uncommon. Herein, we
      present a 26-year-old male student who had accidental acute inhalation exposure
      to a large quantity of titanium ethanolate and hydrogen chloride in chemistry
      lab. He was referred to the emergency department of our hospital with low-grade
      fever, dyspnea, headache, fatigue and myalgia. After 24 hrs of symptomatic
      treatment (oxygen therapy and acetaminophen), the fever was subsided and the
      patient discharged home in a good clinical condition. The presented symptoms
      could be interpreted as a form of metal fume fever. It can therefore be concluded
      that organo-metallic compound of titanium metal may have the potential to produce
      metal fume fever in human. 

PMID- 24748003
TI  - Qat consumption among women living in Yemen.

PMID- 24748004
TI  - Uranium concentration in groundwater in Hisar city, India.

PMID- 24748005
TI  - Sequence heterogeneity in human immunodeficiency virus type 1 nef in patients
      presenting with rapid progression and delayed progression to AIDS.
AB  - Genetic heterogeneity in the nef genes from human immunodeficiency virus type 1
      (HIV-1)-infected rapid progressors (RPs) and long-term nonprogressors (LTNPs) was
      analyzed to identify various amino acid substitutions responsible for the
      discernible difference in disease progression. It was found that the majority of
      the strains characterized belonged to subtype C, followed by several BC
      recombinants and subtype A1. Complete nef subtype C sequences from 33 RPs and
      seven LTNPs were compared, and it was observed that, in the majority of the
      sequences from both groups, highly conserved functional motifs showed subtle
      changes. However, drastic changes were observed in two isolates from LTNPs where
      the arginine cluster was deleted, while in one of them, additionally, acidic
      residues were replaced by basic residues (EEEEE->RK(R)KKE). The deletion of the
      arginine cluster and the mutation of acidic residues to basic residues are
      predicted to delay disease development by abolishing CD4 downmodulation and
      causing diminution of major histocompatibility complex class I (MHC-I)
      downregulation, respectively. Nonetheless, this is an exclusive finding in these
      LTNPs, which necessitates their analysis at the functional level. The synonymous
      to-nonsynonymous substitution ratio was greater than one in both of the groups,
      suggesting amino acid sequence conservation and functional robustness.
      Interpatient nucleotide distance within the group and between the two groups
      showed very little variation, confirming genetic relatedness among isolates.

PMID- 24748006
TI  - Genomic characterization and taxonomic position of a rhabdovirus from a hybrid
      snakehead.
AB  - A new rhabdovirus, tentatively designated as hybrid snakehead rhabdovirus C1207
      (HSHRV-C1207), was first isolated from a moribund hybrid snakehead (Channa
      maculata*Channa argus) in China. We present the complete genome sequence of HSHRV
      C1207 and a comprehensive sequence comparison between HSHRV-C1207 and other
      rhabdoviruses. Sequence alignment and phylogenetic analysis revealed that HSHRV
      C1207 shared the highest degree of homology with Monopterus albus rhabdovirus and
      Siniperca chuatsi rhabdovirus. All three viruses clustered into a single group
      that was distinct from the recognized genera in the family Rhabdoviridae. Our
      analysis suggests that HSHRV-C1207, as well as MARV and SCRV, should be assigned
      to a new rhabdovirus genus.

PMID- 24748007
TI  - Highly resolved intravital striped-illumination microscopy of germinal centers.
AB  - Monitoring cellular communication by intravital deep-tissue multi-photon
      microscopy is the key for understanding the fate of immune cells within thick
      tissue samples and organs in health and disease. By controlling the scanning
      pattern in multi-photon microscopy and applying appropriate numerical algorithms,
      we developed a striped-illumination approach, which enabled us to achieve 3-fold
      better axial resolution and improved signal-to-noise ratio, i.e. contrast, in
      more than 100 um tissue depth within highly scattering tissue of lymphoid organs
      as compared to standard multi-photon microscopy. The acquisition speed as well as
      photobleaching and photodamage effects were similar to standard photo-multiplier
      based technique, whereas the imaging depth was slightly lower due to the use of
      field detectors. By using the striped-illumination approach, we are able to
      observe the dynamics of immune complex deposits on secondary follicular dendritic
      cells - on the level of a few protein molecules in germinal centers. 

PMID- 24748008
TI  - Methods to promote germination of dormant Setaria viridis seeds.
AB  - Setaria viridis has recently emerged as a promising genetic model system to study
      diverse aspects of monocot biology. While the post-germination life cycle of S.
      viridis is approximately 8 weeks long, the prolonged dormancy of freshly
      harvested seeds can more than double the total time required between successive
      generations. Here we describe methods that promote seed germination in S.
      viridis. Our results demonstrate that treating S. viridis seeds with liquid smoke
      or a GA3 and KNO3 solution improves germination rates to 90% or higher even in
      seeds that are 6 days post-harvest with similar results obtained whether seeds
      are planted in soil or on gel-based media. Importantly, we show that these
      treatments have no significant effect on the growth of the adult plant. We have
      tested these treatments on diverse S. viridis accessions and show variation in
      their response. The methods described here will help advance research using this
      model grass species by increasing the pace at which successive generations of
      plants can be analyzed. 

PMID- 24748009
TI  - Risk factors for periprosthetic joint infection after total hip arthroplasty and
      total knee arthroplasty in Chinese patients.
AB  - PURPOSE: The purpose of this hospital-based case-control study was to evaluate
      the risk factors for periprosthetic joint infection (PJI) of total hip
      arthroplasty (THA) and total knee arthroplasty (TKA) in Chinese patients. METHOD:
      From January 2000 to December 2012, 45 patients undergoing THA and TKA who
      developed PJI were recruited for case subjects; controls were 252 without PJI,
      matched by year of index for surgery and type of surgery. Conditional logistic
      regressions were run to compute odds ratios (ORs) and 95% confidence intervals
      (CIs). RESULTS: Demographic factors and comorbid conditions associated with an
      increased adjusted risk of PJI (in decreasing order of significance) were
      diabetes (OR = 5.47, 95% CI: 1.77-16.97; p = 0.003), age (65-75 vs. 45-65 years)
      (OR = 3.36, 95% CI: 1.30-8.69; p = 0.013), BMI (>=28 vs. 18.5-28 kg/m2) (OR =
      2.77, 95% CI: 1.20-6.40; p = 0.017), place of residence (rural) (OR = 2.63, 95%
      CI: 1.13-6.10; p = 0.025) and alcohol abuse (OR = 2.95, 95% CI: 1.06-8.23; p =
      0.039). CONCLUSION: Patients with diabetes, older age, BMI of >=28 kg/m2 and
      alcohol abuse or living in rural areas, had increased PJI risk. Additional
      systematic large-scale studies are needed to verify these results.

PMID- 24748010
TI  - Maternal behaviors promoting language acquisition in slow-to-talk toddlers:
      prospective community-based study.
AB  - OBJECTIVE: To determine, in a community-based sample of slow-to-talk toddlers,
      the extent to which specific maternal responsive behaviors at 24 months predict
      child language at 24 and 36 months. METHODS: Mother-child dyads were recruited
      for this prospective longitudinal study from 3 local government areas spanning
      low, middle, and high socioeconomic status in Melbourne, Australia. At child age
      18 months, 1138 parents completed a 100-word expressive vocabulary checklist; the
      251 (22.1%) children scoring <=20th percentile were then followed up to comprise
      this study. PREDICTORS: Six maternal responsive behaviors (imitations,
      interpretations, labels, expansions, supportive directives and responsive
      questions) were derived from mother-child free-play videos collected at 24 months
      of age and coded using the Observer XT system. OUTCOMES: Expressive and receptive
      language measured at 24 and 36 months of age (Preschool Language Scale-4), blind
      to maternal responsiveness ratings. RESULTS: Two hundred and twenty-six of the
      251 (90.0%) mother-child dyads were followed up at 36 months. In confounder
      adjusted linear regression analyses, expansions, imitations, and responsive
      questions were strongly associated with better receptive and expressive language
      at 24 and 36 months. Labels unexpectedly predicted poorer expressive language at
      36 months. Expansions were the only maternal behavior that predicted improvement
      in language between 24 and 36 months. CONCLUSIONS: Maternal responsive behaviors,
      particularly expansions, offer promise in enhancing early language learning in
      slow-to-talk toddlers. Parent-child interactions characterized by frequent use of
      maternal labels at 24 months could also be a predictive marker of those slow-to
      talk toddlers at greater risk of persistent language problems.

PMID- 24748011
TI  - An 8-year-old biological female who identifies herself as a boy: perspectives in
      primary care and from a parent.
AB  - CASE: An 8-year 8-month-old biological female who self-identifies as a boy,
      Ricardo is brought by his mother for a well-child check to his new pediatrician.
      Ricardo and his mother report that he is doing well, but have concerns about the
      upcoming changes associated with puberty. Ricardo states that he is particularly
      afraid of developing breasts. His mother asks about obtaining a referral to a
      specialist who can provide "hormone therapy" to delay puberty.Ricardo was adopted
      from Costa Rica at the age of 2 as a healthy girl named "Angela." From the age of
      3, he displayed clear preference for male gender-associated clothes, toys, and
      games. At age 5, his mother sought care for hyperactivity and sleep problems. He
      was diagnosed with attention-deficit hyperactivity disorder and sleep onset
      disorder at age 6, and his symptoms have been well controlled with Adderall and
      melatonin.Ricardo lives with his parents who are accepting and supportive of his
      gender preference. He sees a therapist who has experience with gender dysphoria.
      For the past years, he has attended school as male, with the confidential support
      of administrators at his elementary school.

PMID- 24748012
TI  - Clinical models and biochemical predictors of VTE in lung cancer.
AB  - Venous thromboembolism (VTE) is a frequent complication of lung cancer and its
      treatment, especially in the advanced stages of disease. The risk of a pro
      thrombotic state might increase through the activation of hemostasis, occurring
      both via the induction of a pro-coagulant activity and with platelet involvement,
      ultimately leading to the development of metastases. Despite the acknowledgement
      of an increased thrombophilic condition in cancer patients, and the experimental
      evidence that heparin compounds may have direct anticancer benefits, there is no
      univocal consent regarding VTE prevention in cancer outpatients receiving
      therapy. Thus, many authors highlighted the need for the development of
      stratification techniques to identify at-risk patients who might benefit from
      thromboprophylaxis. Clinical risk models were developed and validated, in order
      to assign high-risk patients to a proper thromboprophylaxis regimen that,
      however, might not be justified in all clusters. Besides, efforts have been
      devoted to identify candidate biomarkers that may be used in VTE risk assessment,
      although none has been recognized, so far, as a predictor for VTE in lung cancer
      patients. In this review, we will summarize the latest information concerning
      this very controversial topic, with focus on some of the proposed strategies to
      select the appropriate patients for prophylaxis. 

PMID- 24748013
TI  - Soft tissue artefacts of the human back: comparison of the sagittal curvature of
      the spine measured using skin markers and an open upright MRI.
AB  - Soft tissue artefact affects the determination of skeletal kinematics. Thus, it
      is important to know the accuracy and limitations of kinematic parameters
      determined and modelled based on skin marker data. Here, the curvature angles, as
      well as the rotations of the lumbar and thoracic segments, of seven healthy
      subjects were determined in the sagittal plane using a skin marker set and
      compared to measurements taken in an open upright MRI scanner in order to
      understand the influence of soft tissue artefact at the back. The mean STA in the
      flexed compared to the extended positions were 10.2+/-6.1 mm (lumbar)/9.3+/-4.2
      mm (thoracic) and 10.7+/-4.8 mm (lumbar)/9.2+/-4.9 mm (thoracic) respectively. A
      linear regression of the lumbar and thoracic curvatures between the marker-based
      measurements and MRI-based measurements resulted in coefficients of
      determination, R2, of 0.552 and 0.385 respectively. Skin marker measurements
      therefore allow for the assessment of changes in the lumbar and thoracic
      curvature angles, but the absolute values suffer from uncertainty. Nevertheless,
      this marker set appears to be suitable for quantifying lumbar and thoracic spinal
      changes between quasi-static whole body postural changes. 

PMID- 24748014
TI  - Abstinence versus Moderation Goals in Brief Motivational Treatment for
      Pathological Gambling.
AB  - The present study examined the nature and impact of participant goal selection
      (abstinence versus moderation) in brief motivational treatment for pathological
      gambling via secondary analyses from a randomized controlled trial. The results
      demonstrated that the pattern of goal selection over time could be characterized
      by both fluidity and stability, whereby almost half of participants switched
      their goal at least one time, over 25% of participants selected an unchanging
      goal of 'quit most problematic type of gambling', almost 20% selected an
      unchanging goal of 'quit all types of gambling', and approximately 10% selected
      an unchanging goal of 'gamble in a controlled manner.' The results also
      demonstrated that pretreatment goal selection was uniquely associated with three
      variables, whereby compared to participants who selected the goal to 'cut back on
      problem gambling', those who selected the goal to 'quit problem gambling' were
      more likely to have greater gambling problem severity, to have identified video
      lottery terminal play as problematic, and to have greater motivation to overcome
      their gambling problem. Finally, the results demonstrated that goal selection
      over time had an impact on the average number of days gambled over the course of
      treatment, whereby those with abstinence-based goals gambled significantly fewer
      days than those with moderation-based goals. Nevertheless, goal selection over
      time was not related to dollars gambled, dollars per day gambled, or perceived
      goal achievement. The findings do not support the contention that abstinence
      based goals are more advantageous than moderation goals and are discussed in
      relation to the broader alcohol treatment literature.

PMID- 24748015
TI  - Clinical efficacy and safety of nerve-sparing radical hysterectomy for cervical
      cancer: a systematic review and meta-analysis.
AB  - BACKGROUD AND OBJECTIVE: Nerve-sparing radical hysterectomy (NSRH) may be
      associated with lower postoperative morbidity than radical hysterectomy (RH). We
      aimed to compare the clinical efficacy and safety of abdominal or laparoscopic
      NSRH and RH for treating cervical cancer through systematic review and meta
      analysis. METHODS: PubMed, EMBASE, The Cochrane Library and the Chinese National
      Knowledge Infrastructure databases were systematically searched for all relevant
      studies. Data were abstracted independently by two reviewers. A meta-analysis was
      performed to compare intra- and postoperative outcomes for the two techniques.
      RESULTS: A total of 17 clinical trials were identified. Meta-analysis showed that
      although operating time was significantly longer for abdominal or laparoscopic
      NSRH than for RH, NSRH based on laparotomy or laparoscopy proved more effective
      for postoperative recovery of bladder function. NSRH was also associated with
      lower bladder dysfunction morbidity and fewer postoperative complications. Two
      abdominal trials and one laparoscopic study further suggested that NSRH was
      associated with shorter time to recovery of anal/rectal function. In contrast, RH
      and NSRH based on laparotomy or laparoscopy were similar in terms of extent of
      resection, recurrence rate, survival rate, blood loss and frequency of
      intraoperative complications. The meta-analysis showed that abdominal NSRH was
      not significantly different from RH in length of hospital stay, while one trial
      suggested that length of hospital stay was shorter after laparoscopic NSRH than
      after the corresponding RH. CONCLUSION: NSRH may be a reliable technique for
      treating early cervical cancer. Available evidence suggests that it is better
      than RH for postoperative recovery of pelvic organ function and postoperative
      morbidity, while the two techniques involve similar clinical safety and extent of
      resection. These results should be considered preliminary since they are based on
      a relatively small number of controlled trials, most of which were non
      randomized. The findings should be verified in larger, well-designed studies.

PMID- 24748016
TI  - Response of specific immunoglobulin E to foods in children with atopic
      dermatitis.
AB  - Food allergy is a common condition that plays an important role in the
      pathogenicity and maintenance of atopic dermatitis (AD), however, must be
      carefully investigated before imposing a restrictive diet. The aim of this study
      was to evaluate the sensitivity to foods in patients with AD, correlating it with
      the severity of the disease and other possible associated factors. One hundred
      and eleven children (6-180 months of age) with AD were evaluated and later
      followed up at the Allergy and Clinical Immunology Division, Department of
      Pediatrics at FMABC. The serum concentrations of specific IgE to cow's milk (CM),
      egg, soy, wheat, corn, peanut and fish were measured using an enzymatic
      fluorescence method (ImmunoCAPTM). In order to identify the clinical reactivity,
      the open oral provocation test was performed when specific IgE was positive to
      CM, egg and wheat and in all those who related symptoms after the intake of such
      foods regardless of the presence or absence of sensitization. In total, 40.5 % of
      the studied population was sensitized to at least one food allergen, especially
      those between 73 and 180 months of age. There was a higher prevalence of
      sensitization in children with more severe AD, and foods like CM, egg and wheat
      were the most involved, but with low clinical reactivity. We observed increased
      severity of AD in cases that initiated symptoms earlier and who had shorter
      duration of exclusive breastfeeding as well as a linear increase in sensitization
      in the most serious cases. Serum-specific immunoglobulin E was the only factor
      associated with the relationship that showed sensitization. The occurrence of
      sensitization to foods was frequent, mainly in the age group of 6-9 years and in
      patients with severe AD; however, the validation of the clinical reactivity was
      negative in most of the provocations performed, which agrees with the need to
      prove the same before the imposition of restrictive diets, often unnecessary and
      complex. 

PMID- 24748017
TI  - Psychometric properties of a brief, clinically relevant measure of pain in
      patients with hepatocellular carcinoma.
AB  - PURPOSE: Due to diagnosis at advanced stages, comorbidities, and the impact of
      treatment, patients with hepatocellular carcinoma (HCC) may experience pain. The
      purpose of this study was to evaluate the psychometric properties of a brief,
      clinically relevant measure of pain in HCC. METHODS: We conducted a secondary
      data analysis from four longitudinal studies of patients with HCC (total n =
      304). All patients completed the FACT-Hepatobiliary (FACT-Hep) questionnaire, and
      49 patients completed the Brief Pain Inventory (BPI) Interference scale. We
      conducted confirmatory factor analysis (CFA), Rasch modeling, and correlational
      analysis to assess the psychometrics of the three items on the FACT-Hep that
      assess HCC-relevant pain scale. RESULTS: Patients had an average age of 63.5 (+/
      12.2) and were mostly male (76 %). The mean three-item pain subscale score was
      8.5 +/- 3.0. Seventy-four (24.3 %) patients reported no pain (score = 12).
      Results of a one-factor CFA supported unidimensionality of the items, and all
      items fit the Rasch model. An item-person map demonstrated that the three items
      covered all patients with non-extreme scores. Pain scores were significantly
      associated with baseline general health-related quality of life (FACT-General, r
      = 0.60, p < 0.001) and pain interference (BPI, r = -0.63, p < 0.001).
      CONCLUSIONS: The three FACT-Hep pain items are unidimensional, cover the range of
      pain experienced by most patients with HCC, and demonstrate convergent validity.
      This pain subscale is, if future research demonstrates its sensitivity to change,
      potentially useful for HCC clinical trials.

PMID- 24748018
TI  - Anthracycline-induced cardiotoxicity: a review of pathophysiology, diagnosis, and
      treatment.
AB  - OPINION STATEMENT: Anthracyclines have been widely used in children and adults to
      treat hematologic malignancies, soft-tissue sarcomas, and solid tumors. However,
      anthracyclines come with both short- and long-term cardiotoxic effects, ranging
      from occult changes in myocardial structure and function to severe cardiomyopathy
      and heart failure that may result in cardiac transplantation or death. Here, we
      review the progress made over the past two decades in understanding the molecular
      and genetic basis of anthracycline-induced cardiotoxicity; detecting and
      monitoring myocardial dysfunction; using adjunct cardioprotectant therapies, such
      as dexrazoxane; and improving cardioprotection with agents such as liposomal and
      pegylated doxorubicin. Despite this increased understanding, preventing drug
      induced cardiotoxicity while maintaining oncologic efficacy to achieve the
      highest quality of life over a lifespan remain cornerstones of successful
      anthracycline chemotherapy during childhood.

PMID- 24748019
TI  - Role of magnetic resonance imaging in atrial fibrillation ablation.
AB  - OPINION STATEMENT: Ablation therapy is widely used for treatment of drug
      resistant atrial fibrillation (AF). Ablation success for AF, however, is
      relatively low, often requiring repeated procedures for long-term suppression of
      the arrhythmia. Utilization of imaging techniques that visualize cardiac anatomy,
      function, and tissue characteristics may improve ablation results. Compared to
      other imaging modalities, cardiac magnetic resonance (CMR) has several
      advantages, including the lack of ionizing radiation and unsurpassed soft tissue
      resolution. Chamber morphology images can be registered onto electroanatomic maps
      acquired during the procedure, thus improving procedural safety and efficacy. In
      addition, the ability of CMR to characterize myocardial tissues may optimize
      patient selection for ablation and thromboembolic risk stratification. Post
      procedure CMR can be used to detect potential complications, and with improved
      resolution, it has the potential to assess the integrity of ablation lesions. In
      this paper we will review the role of CMR in the pre-ablation diagnostic workup
      of AF patients as well as during and after catheter ablation.

PMID- 24748020
TI  - Facial transplants in Xenopus laevis embryos.
AB  - Craniofacial birth defects occur in 1 out of every 700 live births, but etiology
      is rarely known due to limited understanding of craniofacial development. To
      identify where signaling pathways and tissues act during patterning of the
      developing face, a 'face transplant' technique has been developed in embryos of
      the frog Xenopus laevis. A region of presumptive facial tissue (the "Extreme
      Anterior Domain" (EAD)) is removed from a donor embryo at tailbud stage, and
      transplanted to a host embryo of the same stage, from which the equivalent region
      has been removed. This can be used to generate a chimeric face where the host or
      donor tissue has a loss or gain of function in a gene, and/or includes a lineage
      label. After healing, the outcome of development is monitored, and indicates
      roles of the signaling pathway within the donor or surrounding host tissues.
      Xenopus is a valuable model for face development, as the facial region is large
      and readily accessible for micromanipulation. Many embryos can be assayed, over a
      short time period since development occurs rapidly. Findings in the frog are
      relevant to human development, since craniofacial processes appear conserved
      between Xenopus and mammals. 

PMID- 24748021
TI  - Developmental and evolutionary history affect survival in stressful environments.
AB  - The world is increasingly impacted by a variety of stressors that have the
      potential to differentially influence life history stages of organisms. Organisms
      have evolved to cope with some stressors, while with others they have little
      capacity. It is thus important to understand the effects of both developmental
      and evolutionary history on survival in stressful environments. We present
      evidence of the effects of both developmental and evolutionary history on
      survival of a freshwater vertebrate, the rough-skinned newt (Taricha granulosa)
      in an osmotically stressful environment. We compared the survival of larvae in
      either NaCl or MgCl2 that were exposed to salinity either as larvae only or as
      embryos as well. Embryonic exposure to salinity led to greater mortality of newt
      larvae than larval exposure alone, and this reduced survival probability was
      strongly linked to the carry-over effect of stunted embryonic growth in salts.
      Larval survival was also dependent on the type of salt (NaCl or MgCl2) the larvae
      were exposed to, and was lowest in MgCl2, a widely-used chemical deicer that,
      unlike NaCl, amphibian larvae do not have an evolutionary history of regulating
      at high levels. Both developmental and evolutionary history are critical factors
      in determining survival in this stressful environment, a pattern that may have
      widespread implications for the survival of animals increasingly impacted by
      substances with which they have little evolutionary history. 

PMID- 24748022
TI  - Different relationships between temporal phylogenetic turnover and phylogenetic
      similarity and in two forests were detected by a new null model.
AB  - BACKGROUND: Ecologists have been monitoring community dynamics with the purpose
      of understanding the rates and causes of community change. However, there is a
      lack of monitoring of community dynamics from the perspective of phylogeny.
      METHODS/PRINCIPLE FINDINGS: We attempted to understand temporal phylogenetic
      turnover in a 50 ha tropical forest (Barro Colorado Island, BCI) and a 20 ha
      subtropical forest (Dinghushan in southern China, DHS). To obtain temporal
      phylogenetic turnover under random conditions, two null models were used. The
      first shuffled names of species that are widely used in community phylogenetic
      analyses. The second simulated demographic processes with careful consideration
      on the variation in dispersal ability among species and the variations in
      mortality both among species and among size classes. With the two models, we
      tested the relationships between temporal phylogenetic turnover and phylogenetic
      similarity at different spatial scales in the two forests. Results were more
      consistent with previous findings using the second null model suggesting that the
      second null model is more appropriate for our purposes. With the second null
      model, a significantly positive relationship was detected between phylogenetic
      turnover and phylogenetic similarity in BCI at a 10 m*10 m scale, potentially
      indicating phylogenetic density dependence. This relationship in DHS was
      significantly negative at three of five spatial scales. This could indicate
      abiotic filtering processes for community assembly. Using variation partitioning,
      we found phylogenetic similarity contributed to variation in temporal
      phylogenetic turnover in the DHS plot but not in BCI plot.
      CONCLUSIONS/SIGNIFICANCE: The mechanisms for community assembly in BCI and DHS
      vary from phylogenetic perspective. Only the second null model detected this
      difference indicating the importance of choosing a proper null model.

PMID- 24748023
TI  - Secondary progressive and relapsing remitting multiple sclerosis leads to motor
      related decreased anatomical connectivity.
AB  - Multiple sclerosis (MS) damages central white matter pathways which has
      considerable impact on disease-related disability. To identify disease-related
      alterations in anatomical connectivity, 34 patients (19 with relapsing remitting
      MS (RR-MS), 15 with secondary progressive MS (SP-MS) and 20 healthy subjects
      underwent diffusion magnetic resonance imaging (dMRI) of the brain. Based on the
      dMRI, anatomical connectivity mapping (ACM) yielded a voxel-based metric
      reflecting the connectivity shared between each individual voxel and all other
      brain voxels. To avoid biases caused by inter-individual brain-shape differences,
      they were estimated in a spatially normalized space. Voxel-based statistical
      analyses using ACM were compared with analyses based on the localized
      microstructural indices of fractional anisotropy (FA). In both RR-MS and SP-MS
      patients, considerable portions of the motor-related white matter revealed
      decreases in ACM and FA when compared with healthy subjects. Patients with SP-MS
      exhibited reduced ACM values relative to RR-MS in the motor-related tracts,
      whereas there were no consistent decreases in FA between SP-MS and RR-MS
      patients. Regional ACM statistics exhibited moderate correlation with clinical
      disability as reflected by the expanded disability status scale (EDSS). The
      correlation between these statistics and EDSS was either similar to or stronger
      than the correlation between FA statistics and the EDSS. Together, the results
      reveal an improved relationship between ACM, the clinical phenotype, and
      impairment. This highlights the potential of the ACM connectivity indices to be
      used as a marker which can identify disease related-alterations due to MS which
      may not be seen using localized microstructural indices. 

PMID- 24748024
TI  - Acute brain trauma in mice followed by longitudinal two-photon imaging.
AB  - Although acute brain trauma often results from head damage in different accidents
      and affects a substantial fraction of the population, there is no effective
      treatment for it yet. Limitations of currently used animal models impede
      understanding of the pathology mechanism. Multiphoton microscopy allows studying
      cells and tissues within intact animal brains longitudinally under physiological
      and pathological conditions. Here, we describe two models of acute brain injury
      studied by means of two-photon imaging of brain cell behavior under posttraumatic
      conditions. A selected brain region is injured with a sharp needle to produce a
      trauma of a controlled width and depth in the brain parenchyma. Our method uses
      stereotaxic prick with a syringe needle, which can be combined with simultaneous
      drug application. We propose that this method can be used as an advanced tool to
      study cellular mechanisms of pathophysiological consequences of acute trauma in
      mammalian brain in vivo. In this video, we combine acute brain injury with two
      preparations: cranial window and skull thinning. We also discuss advantages and
      limitations of both preparations for multisession imaging of brain regeneration
      after trauma. 

PMID- 24748025
TI  - Fecal microbiota transplantation for management of Clostridium difficile
      infection.
AB  - The widespread use of antibiotics has led Clostridium difficile infection (CDI)
      to become a common problem with pronounced medical and economic effects. The
      recurrence of CDI after treatment with standard antibiotics is becoming more
      common with the emergence of more resistant strains of C. difficile. As CDI is an
      antibiotic-associated disease, further treatment with antibiotic is best avoided.
      As the gut flora is severely disturbed in CDI, approaches that restore the gut
      microbiota may become good alternative modes of CDI therapies. Fecal microbiota
      transplantation (FMT) is the procedure of transplantation of fecal bacteria from
      a healthy donor individual into a patient for restoration of the normal colonic
      flora. Thus, FMT helps in the eradication of C. difficile and resolution of
      clinical symptoms such as diarrhea, cramping, and urgency. Though this approach
      to treatment is not new, presently, it has become an alternative and promising
      way of combating infections. The procedure is not in regular use because of the
      time required to identify a suitable donor, the risk of introducing opportunistic
      pathogens, and a general patient aversion to the transplant. However, FMT is
      gaining popularity because of its success rate as a panacea for recurrent attacks
      of CDI and is being increasingly used in clinical practice. This review describes
      the rationale, the indications, the results, the techniques, the potential
      donors, the benefits as well as the complications of fecal microbiota
      instillation to CDI patients in order to restore the normal gut flora. 

PMID- 24748026
TI  - The transport behaviour of elemental mercury DNAPL in saturated porous media:
      analysis of field observations and two-phase flow modelling.
AB  - Mercury is a contaminant of global concern. The use of elemental mercury in
      various (former) industrial processes, such as chlorine production at chlor
      alkali plants, is known to have resulted in soil and groundwater contaminations
      worldwide. However, the subsurface transport behaviour of elemental mercury as an
      immiscible dense non-aqueous phase liquid (DNAPL) in porous media has received
      minimal attention to date. Even though, such insight would aid in the remediation
      effort of mercury contaminated sites. Therefore, in this study a detailed field
      characterization of elemental mercury DNAPL distribution with depth was performed
      together with two-phase flow modelling, using STOMP. This is to evaluate the
      dynamics of mercury DNAPL migration and the controls on its distribution in
      saturated porous media. Using a CPT-probe mounted with a digital camera, in-situ
      mercury DNAPL depth distribution was obtained at a former chlor-alkali-plant,
      down to 9 m below ground surface. Images revealing the presence of silvery
      mercury DNAPL droplets were used to quantify its distribution, characteristics
      and saturation, using an image analysis method. These field-observations with
      depth were compared with results from a one-dimensional two-phase flow model
      simulation for the same transect. Considering the limitations of this approach,
      simulations reasonably reflected the variability and range of the mercury DNAPL
      distribution. To further explore the impact of mercury's physical properties in
      comparison with more common DNAPLs, the migration of mercury and PCE DNAPL in
      several typical hydrological scenarios was simulated. Comparison of the
      simulations suggest that mercury's higher density is the overall controlling
      factor in controlling its penetration in saturated porous media, despite its
      higher resistance to flow due to its higher viscosity. Based on these results the
      hazard of spilled mercury DNAPL to cause deep contamination of groundwater
      systems seems larger than for any other DNAPL.

PMID- 24748027
TI  - Leaching potential of pervious concrete and immobilization of Cu, Pb and Zn using
      pervious concrete.
AB  - This paper investigates the leaching potential of pervious concrete and its
      capacity for immobilizing Cu, Pb and Zn, which are common contaminants in urban
      runoff. Batch experiments showed that the leachability of Cu, Pb and Zn increased
      when pH<8. According to PHREEQC equilibrium modeling, the leaching of major ions
      and trace metals was mainly controlled by the dissolution/precipitation and
      surface complexation reactions, respectively. A 1-D reactive transport experiment
      was undertaken to better understand how pervious concrete might function to
      attenuate contaminant migration. A porous concrete block was sprayed with low pH
      water (pH=4.3+/-0.1) for 190 h. The effluent was highly alkaline (pH~10 to 12).
      In the first 50 h, specific conductance and trace-metal were high but declined
      towards steady state values. PHREEQC modeling showed that mixing of interstitial
      alkaline matrix waters with capillary pore water was required in order to produce
      the observed water chemistry. The interstitial pore solutions seem responsible
      for the high pH values and relatively high concentrations of trace metals and
      major cations in the early stages of the experiment. Finally, pervious concrete
      was sprayed with a synthetic contaminated urban runoff (10 ppb Cu, Pb and Zn)
      with a pH of 4.3+/-0.1 for 135 h. It was found that Pb immobilization was greater
      than either Cu or Zn. Zn is the most mobile among three and also has the highest
      variation in the observed degree of immobilization.

PMID- 24748028
TI  - Wavefront error correction with adaptive optics in diabetic retinopathy.
AB  - PURPOSE: To determine the effects of diabetic retinopathy (DR), increased foveal
      thickness (FT), and adaptive optics (AO) on wavefront aberrations and Shack
      Hartmann (SH) image quality. METHODS: Shack-Hartmann aberrometry and wavefront
      error correction were performed with a bench-top AO retinal imaging system in 10
      healthy control and 19 DR subjects. Spectral domain optical coherence tomography
      was performed and central FT was measured. Based on the FT data in the control
      group, subjects in the DR group were categorized into two subgroups: those with
      normal FT and those with increased FT. Shack-Hartmann image quality was assessed
      based on spot areas, and high-order (HO) root mean square (RMS) and total RMS
      were calculated. RESULTS: There was a significant effect of DR on HO and total
      RMS (p = 0.01), and RMS decreased significantly after AO correction (p < 0.001).
      Shack-Hartmann spot area was significantly affected by DR (p < 0.001), but it did
      not change after AO correction (p = 0.6). High-order RMS, total RMS, and SH spot
      area were higher in DR subjects both before and after AO correction. In DR
      subgroups, HO and total RMS decreased significantly after AO correction (p <
      0.001), whereas the effect of increased FT on HO and total RMS was not
      significant (p >= 0.7). There were no significant effects of increased FT and AO
      on SH spot area (p = 0.9). CONCLUSIONS: Diabetic retinopathy subjects had higher
      wavefront aberrations and less compact SH spots, likely attributable to
      pathological changes in the ocular optics. Wavefront aberrations were
      significantly reduced by AO, although AO performance was suboptimal in DR
      subjects as compared with control subjects.

PMID- 24748029
TI  - Color vision deficits in intermediate age-related macular degeneration.
AB  - PURPOSE: To assess the effect of intermediate age-related macular degeneration
      (AMD) on foveal cone-contrast thresholds. METHODS: We measured L-M and S-cone
      contrast thresholds in subjects with intermediate AMD (n = 10) and age-matched
      control subjects (n = 10). Monocular, foveal 3-degree Gaussian blobs (600
      millisecond raised cosine) were presented at 16 cone ratios throughout L-, M-,
      and S-cone space, and threshold contours were modeled with probability summation
      between two independent detection mechanisms. The role that preretinal absorption
      plays in aging was also evaluated by simulation with FG15 and neutral-density
      filters. RESULTS: Aging results in loss of neural sensitivity, not explained by
      lens changes. On average, intermediate AMD was associated with reduced
      sensitivity in both color and luminance channels (p < 0.05) that appeared to
      indicate greater involvement of S-cones. When data were normalized to age
      expected values, the changes to cone sensitivity were shown to be consistent
      (~200% loss) across L-M, M-L, and S-cone mechanisms. In comparison, the luminance
      (L + M) mechanism showed relative sparing (155% loss, p < 0.05). CONCLUSIONS:
      Eyes with the same phenotype of intermediate AMD can have varying degrees of
      color threshold loss. Functional markers enhance the clinical definition of
      disease expression in AMD.

PMID- 24748030
TI  - A new slit lamp-based technique for anterior chamber angle estimation.
AB  - PURPOSE: To design and test a new noninvasive method for anterior chamber angle
      (ACA) estimation based on the slit lamp that is accessible to all eye-care
      professionals. METHODS: A new technique (slit lamp anterior chamber estimation
      [SLACE]) that aims to overcome some of the limitations of the van Herick
      procedure was designed. The technique, which only requires a slit lamp, was
      applied to estimate the ACA of 50 participants (100 eyes) using two different
      slit lamp models, and results were compared with gonioscopy as the clinical
      standard. RESULTS: The Spearman nonparametric correlation between ACA values as
      determined by gonioscopy and SLACE were 0.81 (p < 0.001) and 0.79 (p < 0.001) for
      each slit lamp. Sensitivity values of 100 and 87.5% and specificity values of 75
      and 81.2%, depending on the slit lamp used, were obtained for the SLACE technique
      as compared with gonioscopy (Spaeth classification). CONCLUSIONS: The SLACE
      technique, when compared with gonioscopy, displayed good accuracy in the
      detection of narrow angles, and it may be useful for eye-care clinicians without
      access to expensive alternative equipment or those who cannot perform gonioscopy
      because of legal constraints regarding the use of diagnostic drugs.

PMID- 24748031
TI  - Differences in neuroretinal function between adult males and females.
AB  - PURPOSE: To determine whether neuroretinal function differs in healthy adult
      males and females younger and older than 50 years. METHODS: This study included
      one eye from each of 50 normal subjects (29 females and 21 males). Neuroretinal
      function was assessed using first-order P1 implicit times (ITs) and N1-P1
      amplitudes (AMPs) obtained from photopic multifocal electroretinograms. To assess
      local differences, retinal maps of local IT and (separately) AMP averages were
      constructed for each subject group. To examine global differences, each subject's
      103 ITs and (separately) AMPs were also averaged to create whole-eye averages.
      Subsequently, retinal maps and whole-eye averages of one subject group were
      compared with those of another. RESULTS: In subjects younger than 50 years,
      neuroretinal function differed significantly between the males and females: local
      ITs were significantly shorter at 83 of 103 tested retinal locations, and whole
      eye IT averages were shorter (p = 0.015) in the males compared with the females.
      In contrast, no analysis indicated that the males and females older than 50 years
      were significantly different. A subanalysis showed that the females who reported
      a hysterectomy (n = 5) had the longest whole-eye ITs of all subject groups (p <=
      0.0013). In the females who did not report a hysterectomy, neuroretinal function
      was worse in the females older than 50 years compared with the females younger
      than 50 years: local ITs were significantly longer at 62 of 103 retinal locations
      tested, and whole-eye IT averages tended to be greater (p = 0.04). Conversely,
      ITs were not statistically different between the younger and older males. N1-P1
      amplitudes did not differ between the sexes. CONCLUSIONS: Multifocal
      electroretinogram IT differs between males and females, depending on the age
      group and hysterectomy status.

PMID- 24748032
TI  - An alkali-burn injury model of corneal neovascularization in the mouse.
AB  - Under normal conditions, the cornea is avascular, and this transparency is
      essential for maintaining good visual acuity. Neovascularization (NV) of the
      cornea, which can be caused by trauma, keratoplasty or infectious disease, breaks
      down the so called 'angiogenic privilege' of the cornea and forms the basis of
      multiple visual pathologies that may even lead to blindness. Although there are
      several treatment options available, the fundamental medical need presented by
      corneal neovascular pathologies remains unmet. In order to develop safe,
      effective, and targeted therapies, a reliable model of corneal NV and
      pharmacological intervention is required. Here, we describe an alkali-burn injury
      corneal neovascularization model in the mouse. This protocol provides a method
      for the application of a controlled alkali-burn injury to the cornea,
      administration of a pharmacological compound of interest, and visualization of
      the result. This method could prove instrumental for studying the mechanisms and
      opportunities for intervention in corneal NV and other neovascular disorders. 

PMID- 24748035
TI  - Trypanosoma cruzi: gene expression surveyed by proteomic analysis reveals
      interaction between different genotypes in mixed in vitro cultures.
AB  - We have analyzed the comportment in in vitro culture of 2 different genotypes of
      Trypanosoma cruzi, the agent of Chagas disease, pertaining to 2 major genetic
      subdivisions (near-clades) of this parasite. One of the stocks was a fast-growing
      one, highly virulent in mice, while the other one was slow-growing, mildly
      virulent in mice. The working hypothesis was that mixtures of genotypes interact,
      a pattern that has been observed by us in empirical experimental studies.
      Genotype mixtures were followed every 7 days and characterized by the DIGE
      technology of proteomic analysis. Proteic spots of interest were characterized by
      the SAMESPOT software. Patterns were compared to those of pure genotypes that
      were also evaluated every 7 days. One hundred and three spots exhibited changes
      in time by comparison with T = 0. The major part of these spots (58%) exhibited
      an under-expression pattern by comparison with the pure genotypes. 32% of the
      spots were over-expressed; 10% of spots were not different from those of pure
      genotypes. Interestingly, interaction started a few minutes after the mixtures
      were performed. We have retained 43 different proteins that clearly exhibited
      either under- or over-expression. Proteins showing interaction were characterized
      by mass spectrometry (MALDI-TOF). Close to 50% of them were either tubulins or
      heat shock proteins. This study confirms that mixed genotypes of T. cruzi
      interact at the molecular level. This is of great interest because mixtures of
      genotypes are very frequent in Chagas natural cycles, both in insect vectors and
      in mammalian hosts, and may play an important role in the transmission and
      severity of Chagas disease. The methodology proposed here is potentially
      applicable to any micropathogen, including fungi, bacteria and viruses. It should
      be of great interest in the case of bacteria, for which the epidemiological and
      clinical consequences of mixed infections could be underestimated.

PMID- 24748036
TI  - Cardiac mechanics in patients with human immunodeficiency virus: a study of
      systolic myocardial deformation in children and young adults.
AB  - Human immunodeficiency virus (HIV) infection causes dysfunction of different
      organ systems. Myocardial diastolic dysfunction has been reported previously in
      an adult HIV population. Our aim was to study myocardial strain in children and
      young adults infected by HIV who have apparently normal ejection fraction. Forty
      HIV-infected patients (mean age 20.6 +/- 1.5 years) with normal ejection fraction
      and 55 matched normal controls (mean age 17 +/- 1.5 years) were studied by two
      dimensional echocardiogram. The images were stored then exported to velocity
      vector imaging software for analysis. Measures considered were left-ventricular
      peak global systolic strain (LV S) and strain rate (LV SR) as well as right
      ventricular peak global systolic strain (RV S) and strain rate (RV SR).
      Circumferential measures of the left ventricle included the following: LV
      circumferential peak global systolic strain (LV circ S), strain rate (LV circ
      SR), radial velocity (LV rad vel), and rotational velocity (LV rot vel) at the
      level of the mitral valve. Statistical significance was set at p < 0.05. The
      means of all longitudinal deformation parameters were significantly lower in HIV
      patients compared with normal controls: LV S (-14.15 vs. -19.31), LV SR (-0.88
      vs. -1.30), RV S (-19.58 vs. -25.09), and RV SR (-1.34 vs. -2.13), respectively
      (p < 0.05). LV rot vel was lower in patients compared with controls (43.23 vs.
      51.71, p = 0.025). LV circ S, LV circ SR, and LV rad vel showed no significant
      difference between the two groups (p >= 0.05). HIV infection affects longitudinal
      systolic cardiac strain and strain rate in children and young adults. Normal
      ejection fraction might be attributed to preserved circumferential myocardial
      deformation. Strain and strain rate may help identify HIV patients at high risk
      for cardiac dysfunction and allow early detection of silent myocardial
      depression.

PMID- 24748033
TI  - Stability of the associations between early life risk indicators and adolescent
      overweight over the evolving obesity epidemic.
AB  - BACKGROUND: Pre- and perinatal factors and preschool body size may help identify
      children developing overweight, but these factors might have changed during the
      development of the obesity epidemic. OBJECTIVE: We aimed to assess the
      associations between early life risk indicators and overweight at the age of 9
      and 15 years at different stages of the obesity epidemic. METHODS: We used two
      population-based Northern Finland Birth Cohorts including 4111 children born in
      1966 (NFBC1966) and 5414 children born in 1985-1986 (NFBC1986). In both cohorts,
      we used the same a priori defined prenatal factors, maternal body mass index
      (BMI), birth weight, infant weight (age 5 months and 1 year), and preschool BMI
      (age 2-5 years). We used internal references in early childhood to define
      percentiles of body size (<50, 50-75, 75-90 and >90) and generalized linear
      models to study the association with overweight, according to the International
      Obesity Taskforce (IOTF) definitions, at the ages of 9 and 15 years. RESULTS: The
      prevalence of overweight at the age of 15 was 9% for children born in 1966 and
      16% for children born in 1986. However, medians of infant weight and preschool
      BMI changed little between the cohorts, and we found similar associations between
      maternal BMI, infant weight, preschool BMI, and later overweight in the two
      cohorts. At 5 years, children above the 90th percentile had approximately a 12
      times higher risk of being overweight at the age of 15 years compared to children
      below the 50th percentile in both cohorts. CONCLUSIONS: The associations between
      early body size and adolescent overweight showed remarkable stability, despite
      the increase in prevalence of overweight over the 20 years between the cohorts.
      Using consequently defined internal percentiles may be a valuable tool in
      clinical practice.

PMID- 24748037
TI  - Transesophageal echocardiography of intracardiac thrombus in congenital heart
      disease and atrial flutter: the importance of thorough examination of the Fontan.
AB  - Transesophageal echocardiography (TEE) is used in atrial flutter or fibrillation
      (AFF) before electric cardioversion to detect intracardiac thrombi. Previous
      studies have described the use of TEE to diagnose intracardiac thrombi in the
      left atrium and left atrial appendage, which has an incidence of 8 % among
      patients without congenital heart disease (CHD). In their practice the authors
      have noted a significant incidence of intracardiac thrombi in other structures of
      patients with CHD and AFF. This study aimed to determine the incidence and
      location of intracardiac thrombi using TEE in patients with CHD requiring
      electric cardioversion of AFF and to compare the use of TEE and transthoracic
      echo (TTE) to detect intracardiac thrombus in this population. A retrospective
      chart review of TEE and TTE findings for all patients with CHD who had electric
      cardioversion of AFF at our institution from 2005 to 2013 was conducted. The
      diagnosis, presence, and location of intracardiac thrombus were determined. The
      TEE and TTE results were compared. The study identified 27 patients with CHD who
      met the study entry criteria at our institution between 2005 and 2013. Seven of
      these patients had a single ventricle with Fontan palliation. All the patients
      presented with AFF and had TEE before electric cardioversion. No patients were
      excluded from the study. The patients ranged in age from 2 to 72 years (median,
      21 years) and weighed 17-100 kg (median, 65 kg). The duration of AFF before TEE
      and attempted cardioversion ranged from 1 day to 3 weeks (median, 3.5 days).
      Intracardiac thrombus was present in 18 % (5/27) of the patients and in 57 %
      (4/7) of the Fontan patients with AFF. No embolic events were reported acutely or
      during a 6-month follow-up period. Among patients with CHD who present with AFF,
      a particularly high incidence of intracardiac thrombi is present in the Fontan
      patients that may be difficult to detect by TTE. Thorough TEE examination of the
      Fontan and related structures is indicated before electric cardioversion of AFF.
      The incidence of intracardiac thrombus in CHD patients is more than double that
      reported in non-CHD patients.

PMID- 24748038
TI  - Percutaneous angioplasty used to manage native and recurrent coarctation of the
      aorta in infants younger than 1 year: immediate and midterm results.
AB  - Balloon angioplasty (BAP) used to manage native coarctation of the aorta (CoAo)
      in infants remains controversial. This study aimed to compare short- and midterm
      results of BAP between native CoAo (NaCo) and postsurgical recoarctations (ReCo)
      in infants younger than 1 year. This retrospective study compared the clinical,
      echocardiographic, hemodynamic, and angiographic data for infants who underwent
      BAP between July 2003 and September 2012. The 12 NaCo and 13 ReCo patients in
      this study underwent BAP at 4.61 +/- 3.69 and 4.88 +/- 3.07 months (p = 0.84) and
      weighed 5.49 +/- 2.57 and 6.10 +/- 2.11 kg (p = 0.52), respectively. Their
      respective heights were 60.58 +/- 10.58 and 61.15 +/- 6.74 cm (p = 0.87). All the
      ReCo patients had their initial surgery before the age of 3 months. The minimal
      CoAo diameter was 2.81 +/- 0.96 mm in the NaCo group and 2.86 +/- 1.0 mm in the
      ReCo group (p = 0.90). The relative gradient reduction was 62.79 +/- 32.43 % in
      the NaCo group and 73.37 +/- 20.78 % in the ReCo group (p = 0.33). The in situ
      complication rate (pseudoaneurysm) was 8.33 % in the NaCo group and 7.69 % in the
      ReCo group (p = 0.74). During the early follow-up evaluation, five NaCo patients
      (41.66 %) presented with recoarctation requiring BAP reintervention within 1.75
      +/- 1.41 months (all had their initial BAP before 3 months of age) compared with
      1 ReCo patient (7.69 %) (p = 0.165). The mean follow-up period was 3.09 +/- 2.69
      years for the NaCo patients and 3.6 +/- 3.18 years for the ReCo patients (p =
      0.69), during which the blood pressure gradient was 12.33 +/- 9.67 for the NaCo
      patients and 7.80 +/- 8.78 for the ReCo patients (p = 0.17), with corresponding
      Doppler peak instantaneous gradients of 21.29 +/- 11.19 and 16.20 +/- 10.23 (p =
      0.24). The resultant diameter ratio between the minimal isthmus diameter and the
      aortic diameter at the diaphragmatic level was 0.81 +/- 0.15 in the NaCo group
      and 0.85 +/- 0.12 in the ReCo group (p = 0.53). The immediate and midterm results
      of BAP for the NaCo and ReCo infants were comparable. Accordingly, BAP seems to
      be an acceptable alternative to surgery for infants older than 3 months.

PMID- 24748039
TI  - Blind manuscript submission to reduce rejection bias?

PMID- 24748040
TI  - Nitrogen-Sparing Mechanisms in Chlamydomonas: Reduce, Reuse, Recycle, and
      Reallocate.

PMID- 24748041
TI  - The Cyanobacterial Photoactive Orange Carotenoid Protein Is an Excellent Singlet
      Oxygen Quencher.
AB  - Cyanobacteria have developed a photoprotective mechanism that decreases the
      energy arriving at the photosynthetic reaction centers under high-light
      conditions. The photoactive orange carotenoid protein (OCP) is essential in this
      mechanism as a light sensor and energy quencher. When OCP is photoactivated by
      strong blue-green light, it is able to dissipate excess energy as heat by
      interacting with phycobilisomes. As a consequence, charge separation and
      recombination leading to the formation of singlet oxygen diminishes. Here, we
      demonstrate that OCP has another essential role. We observed that OCP also
      protects Synechocystis cells from strong orange-red light, a condition in which
      OCP is not photoactivated. We first showed that this photoprotection is related
      to a decrease of singlet oxygen concentration due to OCP action. Then, we
      demonstrated that, in vitro, OCP is a very good singlet oxygen quencher. By
      contrast, another carotenoid protein having a high similarity with the N-terminal
      domain of OCP is not more efficient as a singlet oxygen quencher than a protein
      without carotenoid. Although OCP is a soluble protein, it is able to quench the
      singlet oxygen generated in the thylakoid membranes. Thus, OCP has dual and
      complementary photoprotective functions as an energy quencher and a singlet
      oxygen quencher.

PMID- 24748042
TI  - The Enzyme-Like Domain of Arabidopsis Nuclear beta-Amylases Is Critical for DNA
      Sequence Recognition and Transcriptional Activation.
AB  - Plant BZR1-BAM transcription factors contain a beta-amylase (BAM)-like domain,
      characteristic of proteins involved in starch breakdown. The enzyme-derived
      domains appear to be noncatalytic, but they determine the function of the two
      Arabidopsis thaliana BZR1-BAM isoforms (BAM7 and BAM8) during transcriptional
      initiation. Removal or swapping of the BAM domains demonstrates that the BAM7 BAM
      domain restricts DNA binding and transcriptional activation, while the BAM8 BAM
      domain allows both activities. Furthermore, we demonstrate that BAM7 and BAM8
      interact on the protein level and cooperate during transcriptional regulation.
      Site-directed mutagenesis of residues in the BAM domain of BAM8 shows that its
      function as a transcriptional activator is independent of catalysis but requires
      an intact substrate binding site, suggesting it may bind a ligand. Microarray
      experiments with plants overexpressing truncated versions lacking the BAM domain
      indicate that the pseudo-enzymatic domain increases selectivity for the preferred
      cis-regulatory element BBRE (BZR1-BAM Responsive Element). Side specificity
      toward the G-box may allow crosstalk to other signaling networks. This work
      highlights the importance of the enzyme-derived domain of BZR1-BAMs, supporting
      their potential role as metabolic sensors.

PMID- 24748043
TI  - The ARC1 E3 Ligase Promotes Two Different Self-Pollen Avoidance Traits in
      Arabidopsis.
AB  - Flowering plants have evolved various strategies for avoiding self-pollen to
      drive genetic diversity. These strategies include spatially separated sexual
      organs (herkogamy), timing differences between male pollen release and female
      pistil receptivity (dichogamy), and self-pollen rejection. Within the
      Brassicaceae, these outcrossing systems are the evolutionary default state, and
      many species display these traits, including Arabidopsis lyrata. In contrast to
      A. lyrata, closely related Arabidopsis thaliana has lost these self-pollen traits
      and thus represents an excellent system to test genes for reconstructing these
      evolutionary traits. We previously demonstrated that the ARC1 E3 ligase is
      required for self-incompatibility in two diverse Brassicaceae species, Brassica
      napus and A. lyrata, and is frequently deleted in self-compatible species,
      including A. thaliana. In this study, we examined ARC1's requirement for
      reconstituting self-incompatibility in A. thaliana and uncovered an important
      role for ARC1 in promoting a strong and stable pollen rejection response when
      expressed with two other A. lyrata self-incompatibility factors. Furthermore, we
      discovered that ARC1 promoted an approach herkogamous phenotype in A. thaliana
      flowers. Thus, ARC1's expression resulted in two different A. lyrata traits for
      self-pollen avoidance and highlights the key role that ARC1 plays in the
      evolution and retention of outcrossing systems.

PMID- 24748045
TI  - Expression of leukocyte adhesion-related glycosyltransferase genes in acute
      coronary syndrome patients.
AB  - INTRODUCTION: Acute coronary syndrome (ACS) is caused by destabilization and
      rupture of atherosclerotic plaque in the coronary artery via mechanisms affecting
      leukocyte signaling, rolling, adhesion, extravasation and inflammation-promoting
      factors. The majority of cellular communication takes place on the membrane
      surface that is covered with glycoproteins and glycolipids synthesized by
      glycosyltransferases. The aim of this study was to determine the mRNA expression
      of leukocyte adhesion-related glycosyltransferases in patients during the onset
      and the chronic phase of ACS and to compare the expression with matching subjects
      without coronary disease. SUBJECTS AND METHODS: The study included 26 ACS
      patients and 26 ACS-free matched-pair controls. Blood samples were collected at
      the time of hospital admittance and 8 days later. Expression analysis of six
      fucosyltransferases and six sialyltransferases was performed by a real-time
      polymerase chain reaction. RESULTS: At the time of admittance ACS subjects had
      lower expression levels of FUT4, ST6GalNac4, ST6Gal1 and GM3 synthase (p < 0.05)
      than the control subjects, and moreover, after 8 days down-regulation of FUT7 and
      ST6GalNac3 was also observed (p < 0.05). When compared to the initial gene
      expression, after treatment and stabilization of ACS subjects, FUT7, ST6GalNac2
      and ST6GalNac3 were down-regulated, whereas ST6GalNac1 was up-regulated.
      Expression levels of FUT7, ST6GalNac1, ST6GalNac2 and ST6GalNac3 were predicted
      by several drugs and medical history. CONCLUSION: Expression of
      glycosyltransferase genes differs in ACS and control subjects. During the course
      of the ACS study we established further changes in gene expression levels.
      Medical history was predictive of gene expression levels while drugs were shown
      to modulate expression levels.

PMID- 24748044
TI  - Nitrogen-Sparing Mechanisms in Chlamydomonas Affect the Transcriptome, the
      Proteome, and Photosynthetic Metabolism.
AB  - Nitrogen (N) is a key nutrient that limits global primary productivity; hence, N
      use efficiency is of compelling interest in agriculture and aquaculture. We used
      Chlamydomonas reinhardtii as a reference organism for a multicomponent analysis
      of the N starvation response. In the presence of acetate, respiratory metabolism
      is prioritized over photosynthesis; consequently, the N-sparing response targets
      proteins, pigments, and RNAs involved in photosynthesis and chloroplast function
      over those involved in respiration. Transcripts and proteins of the Calvin-Benson
      cycle are reduced in N-deficient cells, resulting in the accumulation of cycle
      metabolic intermediates. Both cytosolic and chloroplast ribosomes are reduced,
      but via different mechanisms, reflected by rapid changes in abundance of RNAs
      encoding chloroplast ribosomal proteins but not cytosolic ones. RNAs encoding
      transporters and enzymes for metabolizing alternative N sources increase in
      abundance, as is appropriate for the soil environmental niche of C. reinhardtii.
      Comparison of the N-replete versus N-deplete proteome indicated that abundant
      proteins with a high N content are reduced in N-starved cells, while the proteins
      that are increased have lower than average N contents. This sparing mechanism
      contributes to a lower cellular N/C ratio and suggests an approach for
      engineering increased N-use efficiency.

PMID- 24748046
TI  - Physcomitrella patens has kinase-LRR R gene homologs and interacting proteins.
AB  - Plant disease resistance gene (R gene)-like sequences were screened from the
      Physcomitrella patens genome. We found 603 kinase-like, 475 Nucleotide Binding
      Site (NBS)-like and 8594 Leucine Rich Repeat (LRR)-like sequences by homology
      searching using the respective domains of PpC24 (Accession No. BAD38895), which
      is a candidate kinase-NBS-LRR (kinase-NL) type R-like gene, as a reference. The
      positions of these domains in the genome were compared and 17 kinase-NLs were
      predicted. We also found four TIR-NBS-LRR (TIR-NL) sequences with homology to
      Arabidopsis TIR-NL (NM_001125847), but three out of the four TIR-NLs had
      tetratricopeptide repeats or a zinc finger domain in their predicted C-terminus.
      We also searched for kinase-LRR (KLR) type sequences by homology with rice OsXa21
      and Arabidopsis thaliana FLS2. As a result, 16 KLRs with similarity to OsXa21
      were found. In phylogenetic analysis of these 16 KLRs, PpKLR36, PpKLR39, PpKLR40,
      and PpKLR43 formed a cluster with OsXa21. These four PpKLRs had deduced
      transmembrane domain sequences and expression of all four was confirmed. We also
      found 14 homologs of rice OsXB3, which is known to interact with OsXa21 and is
      involved in signal transduction. Protein-protein interaction was observed between
      the four PpKLRs and at least two of the XB3 homologs in Y2H analysis. 

PMID- 24748047
TI  - Feasibility and safety of intracoronary nicorandil infusion as a novel hyperemic
      agent for fractional flow reserve measurements.
AB  - Fractional flow reserve (FFR) is a useful modality to assess the functional
      significance of coronary stenoses. Although adenosine triphosphate (ATP) is
      generally used as the hyperemic stimulus, we sometimes encounter adverse events
      like hypotension during FFR measurement. Nicorandil, an ATP-sensitive potassium
      channel opener, recognized as an epicardial and resistance vessel dilator, has
      not been fully evaluated as a possible alternative hyperemic agent. The aim of
      this study was to evaluate the feasibility and safety of intracoronary nicorandil
      infusion compared to intravenous ATP for FFR measurement in patients with
      coronary artery disease. A total of 102 patients with 124 intermediate lesions
      (diameter stenosis >40 and <70% by visual assessment) were enrolled. All vessels
      underwent FFR measurements with both ATP (150 MUg/kg/min) and nicorandil (2.0 mg)
      stimulus. FFR, hemodynamic values, and periprocedural adverse events between the
      two groups were evaluated. A strong correlation was observed between FFR with ATP
      and FFR with nicorandil (r = 0.954, p < 0.001). The agreement between the two
      sets of measurements was also high, with a mean difference of 0.01 +/- 0.03. The
      mean aortic pressure drop during pharmacological stimulus was significantly
      larger with ATP compared to nicorandil (9.6 +/- 9.6 vs. 5.5 +/- 5.8 mmHg, p <
      0.001). During FFR measurement, transient atrioventricular block was frequently
      observed with ATP compared to nicorandil (4.0 vs. 0%, p = 0.024). This study
      suggests that intracoronary nicorandil infusion is associated with clinical
      utility and safety compared to ATP as an alternative hyperemic agent for FFR
      measurement.

PMID- 24748048
TI  - Bradyarrhythmias may induce central sleep apnea in a patient with obstructive
      sleep apnea.
AB  - The relationship between central sleep apnea (CSA) and bradyarrhythmia remains
      unclear. We report the case of a 70-year-old man with severe obstructive sleep
      apnea and bradyarrhythmia due to sick sinus syndrome in whom concomitant CSA was
      alleviated after pacemaker implantation. 

PMID- 24748049
TI  - Seroprevalence of Japanese encephalitis virus infection in captive Japanese
      macaques (Macaca fuscata).
AB  - Japanese encephalitis virus (JEV), which is transmitted by mosquitoes, infects
      many animal species and causes serious acute encephalitis in humans and horses.
      In this study, a serosurvey of JEV in Japanese macaques (Macaca fuscata) reared
      in Aichi Prefecture was conducted using purified JEV as an antigen for ELISA. The
      results revealed that 146 of 332 monkeys (44 %) were seropositive for JEV. In
      addition, 35 of 131 monkeys (27 %) born in the facility were seropositive, and
      the annual infection rate in the facility was estimated as 13 %. Our results
      provide evidence of the frequent exposure of many Japanese macaques to JEV,
      suggesting that there is a risk of JEV transmission to humans by mosquitoes. 

PMID- 24748050
TI  - Direct penetrating and indirect neck trauma as a cause of internal carotid artery
      thrombosis and secondary ischemic stroke.
AB  - The following manuscript presents two cases of ischemic stroke secondary to
      traumatic internal carotid artery thrombosis with concomitant middle cerebral
      artery thrombosis occurring very rarely in the medico-legal practice. Penetrating
      neck trauma due to an occupational accident and multiple head and neck trauma
      secondary to battery were described. The autopsy and histopathological
      examination as well as the analysis of available medical records, including
      radiological examinations, and records of investigation indicated the sustained
      trauma to be the cause of the thrombosis. 

PMID- 24748051
TI  - Initiation of metastatic breast carcinoma by targeting of the ductal epithelium
      with adenovirus-cre: a novel transgenic mouse model of breast cancer.
AB  - Breast cancer is a heterogeneous disease involving complex cellular interactions
      between the developing tumor and immune system, eventually resulting in
      exponential tumor growth and metastasis to distal tissues and the collapse of
      anti-tumor immunity. Many useful animal models exist to study breast cancer, but
      none completely recapitulate the disease progression that occurs in humans. In
      order to gain a better understanding of the cellular interactions that result in
      the formation of latent metastasis and decreased survival, we have generated an
      inducible transgenic mouse model of YFP-expressing ductal carcinoma that develops
      after sexual maturity in immune-competent mice and is driven by consistent,
      endocrine-independent oncogene expression. Activation of YFP, ablation of p53,
      and expression of an oncogenic form of K-ras was achieved by the delivery of an
      adenovirus expressing Cre-recombinase into the mammary duct of sexually mature,
      virgin female mice. Tumors begin to appear 6 weeks after the initiation of
      oncogenic events. After tumors become apparent, they progress slowly for
      approximately two weeks before they begin to grow exponentially. After 7-8 weeks
      post-adenovirus injection, vasculature is observed connecting the tumor mass to
      distal lymph nodes, with eventual lymphovascular invasion of YFP+ tumor cells to
      the distal axillary lymph nodes. Infiltrating leukocyte populations are similar
      to those found in human breast carcinomas, including the presence of alphabeta
      and gammadelta T cells, macrophages and MDSCs. This unique model will facilitate
      the study of cellular and immunological mechanisms involved in latent metastasis
      and dormancy in addition to being useful for designing novel immunotherapeutic
      interventions to treat invasive breast cancer. 

PMID- 24748052
TI  - Continuing evolution of equine influenza virus in Central Asia, 2007-2012.
AB  - Equine influenza (EI) continues to be an important respiratory pathogen of horses
      worldwide. Since 2007 several outbreaks of EI have occurred in Central Asian
      countries, including Kazakhstan, western Mongolia, India and western China.
      Phylogenetic analysis showed that two H3N8 equine influenza virus (EIV) isolates
      from Kazakhstan, A/equine/Almaty/26/2007 and A/equine/South Kazakhstan/236/12,
      were related to Florida sublineage 2, with high similarity to EIVs circulating in
      the same period in neighbouring countries. New outbreaks of EI during 2011 and
      2012 in Kazakhstan and other Central Asian countries were caused by viruses of
      the same lineage. Genetic characterization of the viruses showed formation of a
      small EIV cluster with specific genetic signatures and continued evolution of
      this lineage in Central Asia between 2007 and 2012. The main genetic changes were
      observed in hemagglutinin gene without any antigenic drift. Although no
      vaccination policy was carried out in Kazakhstan, application of Florida clade 2
      based vaccines is recommended. 

PMID- 24748053
TI  - Transcriptome-wide identification of bread wheat WRKY transcription factors in
      response to drought stress.
AB  - The WRKY superfamily of transcription factors was shown to be involved in biotic
      and abiotic stress responses in plants such as wheat (Triticum aestivum L.), one
      of the major crops largely cultivated and consumed all over the world. Drought is
      an important abiotic stress resulting in a considerable amount of loss in
      agronomical yield. Therefore, identification of drought responsive WRKY members
      in wheat has a profound significance. Here, a total of 160 TaWRKY proteins were
      characterized according to sequence similarity, motif varieties, and their
      phylogenetic relationships. The conserved sequences of the TaWRKYs were aligned
      and classified into three main groups and five subgroups. A novel motif in wheat,
      WRKYGQR, was identified. To putatively determine the drought responsive TaWRKY
      members, publicly available RNA-Seq data were analyzed for the first time in this
      study. Through in silico searches, 35 transcripts were detected having an
      identity to ten known TaWRKY genes. Furthermore, relative expression levels of
      TaWRKY16/TaWRKY16-A, TaWRKY17, TaWRKY19-C, TaWRKY24, TaWRKY59, TaWRKY61, and
      TaWRKY82 were measured in root and leaf tissues of drought-tolerant Sivas 111/33
      and susceptible Atay 85 cultivars. All of the quantified TaWRKY transcripts were
      found to be up-regulated in root tissue of Sivas 111/33. Differential expression
      of TaWRKY16, TaWRKY24, TaWRKY59, TaWRKY61 and TaWRKY82 genes was discovered for
      the first time upon drought stress in wheat. These comprehensive analyses bestow
      a better understanding about the WRKY TFs in bread wheat under water deficit, and
      increased number of drought responsive WRKYs would contribute to the molecular
      breeding of tolerant wheat cultivars. 

PMID- 24748054
TI  - Factors associated with access to sexual health services among teens in toronto:
      does immigration matter?
AB  - This manuscript explores predictors of access to sexual health services among
      urban immigrant adolescents who live in Toronto, Canada. Surveys (n = 1216) were
      collected from pre-existing youth groups in community settings. A binary logistic
      multivariate model was developed to examine associations between access to sexual
      health services and a series of individual, interpersonal, and structural
      variables. Sexual activity, age, race, and social resources each had significant
      partial impact on access to sexual health services. Among young women, those with
      more social resources had significantly accessed services more often than those
      with fewer resources, but among men there was no difference as a function of
      social resources. Although immigration predicted access to sexual health services
      on its own, it was not statistically significant in this model when other
      variables were included. Immigration status, in and of itself, was not a
      predictor of youth's access to sexual health services. The impact of immigration
      status appears to occur because of its association with other variables, such as
      race. Implications for practice are discussed.

PMID- 24748055
TI  - Viability and gene expression responses to polymeric nanoparticles in human and
      rat cells.
AB  - Applications of polymeric nanoparticles (NP) in medical fields are rapidly
      expanding. However, the influence of polymeric NP on cell growth and functions is
      widely underestimated. Therefore, we have studied cell and polymeric NP
      interactions by addressing two cell types with two endpoints (viability and gene
      expressions). Rat NR8383 and human THP-1 monocytic cell lines were exposed to 6
      to 200 MUg/mL of Eudragit((r)) RL NP for 24 h, and cellular viability was
      estimated using MTT, WST-1, and trypan blue tests. A decrease of viability was
      observed with NR8383 cells (down to 70% for 200 MUg/mL), and on the contrary, an
      increase with THP-1 cells (up to 140% for 200 MUg/mL). Differential expression of
      genes involved in oxidative damage (NCF1), inflammation (NFKB, TNFA, IL6, IL1B),
      autophagy (ATG16L), and apoptotic balance (PDCD4, BCL2, CASP8) was analyzed.
      ATG16L, BCL2, and TNFA were up-regulated in NR8383 cells, which are consistent
      with an induction of autophagy and inflammation. On the other hand, NCF1, NFKB,
      and IL1B were down-regulated in THP-1 cells, which may contribute to explain the
      increase of cellular viability. Our results show that (1) the toxic potency of NP
      is dependent on the cellular model used and (2) mechanistic toxicology should be
      the corner stone for the evaluation of NP hazard.

PMID- 24748056
TI  - Development of an umami taste sensitivity test and its clinical use.
AB  - There is a close relationship between perception of umami, which has become
      recognized as the fifth taste, and the human physical condition. We have
      developed a clinical test for umami taste sensitivity using a filter paper disc
      with a range of six monosodium glutamate (MSG) concentrations. We recruited 28
      patients with taste disorders (45-78 years) and 184 controls with no taste
      disorders (102 young [18-25 years] and 82 older [65-89 years] participants).
      Filter paper discs (5 mm dia.) were soaked in aqueous MSG solutions (1, 5, 10,
      50, 100 and 200 mM), then placed on three oral sites innervated by different
      taste nerves. The lowest concentration participants correctly identified was
      defined as the recognition threshold (RT) for MSG. This test showed good
      reproducibility for inter- and intra-observer variability. We concluded that: (1)
      The RT of healthy controls differed at measurement sites innervated by different
      taste nerves; that is, the RT of the anterior tongue was higher than that of
      either the posterior tongue or the soft palate in both young and older
      individuals. (2) No significant difference in RT was found between young adults
      and older individuals at any measurement site. (3) The RT of patients with taste
      disorders was higher before treatment than that of the healthy controls at any
      measurement site. (4) The RT after treatment in these patients improved to the
      same level as that of the healthy controls. (5) The cutoff values of RT, showing
      the highest diagnostic accuracy (true positives + true negatives), were 200 mM
      MSG for AT and 50 mM MSG for PT and SP. The diagnostic accuracy at these cutoff
      values was 0.92, 0.87 and 0.86 for AT, PT and SP, respectively. Consequently,
      this umami taste sensitivity test is useful for discriminating between normal and
      abnormal umami taste sensations. 

PMID- 24748057
TI  - Inferring cell-scale signalling networks via compressive sensing.
AB  - Signalling network inference is a central problem in system biology. Previous
      studies investigate this problem by independently inferring local signalling
      networks and then linking them together via crosstalk. Since a cellular
      signalling system is in fact indivisible, this reductionistic approach may have
      an impact on the accuracy of the inference results. Preferably, a cell-scale
      signalling network should be inferred as a whole. However, the holistic approach
      suffers from three practical issues: scalability, measurement and overfitting.
      Here we make this approach feasible based on two key observations: 1) variations
      of concentrations are sparse due to separations of timescales; 2) several species
      can be measured together using cross-reactivity. We propose a method, CCELL, for
      cell-scale signalling network inference from time series generated by
      immunoprecipitation using Bayesian compressive sensing. A set of benchmark
      networks with varying numbers of time-variant species is used to demonstrate the
      effectiveness of our method. Instead of exhaustively measuring all individual
      species, high accuracy is achieved from relatively few measurements. 

PMID- 24748058
TI  - Evolution of bacterial consortia in spontaneously started rye sourdoughs during
      two months of daily propagation.
AB  - The evolution of bacterial consortia was studied in six semi-solid rye sourdoughs
      during long-term backslopping at different temperatures. Each rye sourdough was
      started spontaneously in a laboratory (dough yield 200), propagated at either 20
      degrees C or 30 degrees C, and renewed daily at an inoculation rate of 1?10 for
      56 days. The changes in bacterial diversity over time were followed by both DGGE
      coupled with partial 16S rRNA gene sequencing and pyrosequencing of bar-coded 16S
      rRNA gene amplicons. Four species from the genus Lactobacillus (brevis,
      crustorum, plantarum, and paralimentarius) were detected in different
      combinations in all sourdoughs after 56 propagation cycles. Facultative
      heterofermentative lactic acid bacteria dominated in sourdoughs fermented at 30
      degrees C, while both obligate and facultative heterofermentative LAB were found
      to dominate in sourdoughs fermented at 20 degrees C. After 56 propagation cycles,
      Kazachstania unispora (formerly Saccharomyces unisporus) was identified as the
      only yeast species that dominated in sourdoughs fermented at 20 degrees C, while
      different combinations of strains from four yeast species (Kazachstania unispora,
      Saccharomyces cerevisiae, Candida krusei and Candida glabrata) were detected in
      sourdoughs propagated at 30 degrees C. The evolution of bacterial communities in
      sourdoughs fermented at the same temperature did not follow the same time course
      and changes in the composition of dominant and subdominant bacterial communities
      occurred even after six weeks of backslopping. 

PMID- 24748059
TI  - Comparative transcriptome analysis of short fiber mutants Ligon-lintless 1 and 2
      reveals common mechanisms pertinent to fiber elongation in cotton (Gossypium
      hirsutum L.).
AB  - Understanding the molecular processes affecting cotton (Gossypium hirsutum) fiber
      development is important for developing tools aimed at improving fiber quality.
      Short fiber cotton mutants Ligon-lintless 1 (Li1) and Ligon-lintless 2 (Li2) are
      naturally occurring, monogenic mutations residing on different chromosomes. Both
      mutations cause early cessation in fiber elongation. These two mutants serve as
      excellent model systems to elucidate molecular mechanisms relevant to fiber
      length development. Previous studies of these mutants using transcriptome
      analysis by our laboratory and others had been limited by the fact that very
      large numbers of genes showed altered expression patterns in the mutants, making
      a targeted analysis difficult or impossible. In this research, a comparative
      microarray analysis was conducted using these two short fiber mutants and their
      near isogenic wild type (WT) grown under both field and greenhouse environments
      in order to identify key genes or metabolic pathways common to fiber elongation.
      Analyses of three transcriptome profiles obtained from different growth
      conditions and mutant types showed that most differentially expressed genes
      (DEGs) were affected by growth conditions. Under field conditions, short fiber
      mutants commanded higher expression of genes related to energy production,
      manifested by the increasing of mitochondrial electron transport activity or
      responding to reactive oxygen species when compared to the WT. Eighty-eight DEGs
      were identified to have altered expression patterns common to both short fiber
      mutants regardless of growth conditions. Enrichment, pathway and expression
      analyses suggested that these 88 genes were likely involved in fiber elongation
      without being affected by growth conditions. 

PMID- 24748060
TI  - Extending cancer prevention to improve fruit and vegetable consumption.
AB  - Consuming a diet that is rich in fruits and vegetables is critical for preventing
      cancer and cancer-related disparities. Food systems approaches that increase
      spatial-temporal, economic, and social access to fruits and vegetables may
      ultimately result in improved consumption patterns among Americans. Engaging the
      triad of Cooperative Extension Services, public health systems, and community
      health centers may yield maximal public health benefits from food systems
      interventions. These entities have a mutual interest in promoting health equity
      and community and economic vitality that provides common ground to (a) implement
      solutions through the dissemination of evidence-based programs and (b) share
      resources to foster grassroots support for sustained change. Working together,
      these systems have an unprecedented opportunity to build on their common ground
      to implement, evaluate, and disseminate evidence-based food systems interventions
      in communities and with populations experiencing disparate risk for cancer and
      cancer-related diseases. 

PMID- 24748061
TI  - A protocol for conducting rainfall simulation to study soil runoff.
AB  - Rainfall is a driving force for the transport of environmental contaminants from
      agricultural soils to surficial water bodies via surface runoff. The objective of
      this study was to characterize the effects of antecedent soil moisture content on
      the fate and transport of surface applied commercial urea, a common form of
      nitrogen (N) fertilizer, following a rainfall event that occurs within 24 hr
      after fertilizer application. Although urea is assumed to be readily hydrolyzed
      to ammonium and therefore not often available for transport, recent studies
      suggest that urea can be transported from agricultural soils to coastal waters
      where it is implicated in harmful algal blooms. A rainfall simulator was used to
      apply a consistent rate of uniform rainfall across packed soil boxes that had
      been prewetted to different soil moisture contents. By controlling rainfall and
      soil physical characteristics, the effects of antecedent soil moisture on urea
      loss were isolated. Wetter soils exhibited shorter time from rainfall initiation
      to runoff initiation, greater total volume of runoff, higher urea concentrations
      in runoff, and greater mass loadings of urea in runoff. These results also
      demonstrate the importance of controlling for antecedent soil moisture content in
      studies designed to isolate other variables, such as soil physical or chemical
      characteristics, slope, soil cover, management, or rainfall characteristics.
      Because rainfall simulators are designed to deliver raindrops of similar size and
      velocity as natural rainfall, studies conducted under a standardized protocol can
      yield valuable data that, in turn, can be used to develop models for predicting
      the fate and transport of pollutants in runoff. 

PMID- 24748062
TI  - Patient self-management of oral anticoagulation with vitamin K antagonists in
      everyday practice: efficacy and safety in a nationwide long-term prospective
      cohort study.
AB  - Patient self-management (PSM) of oral anticoagulation is under discussion,
      because evidence from real-life settings is missing. Using data from a
      nationwide, prospective cohort study in Switzerland, we assessed overall long
      term efficacy and safety of PSM and examined subgroups. Data of 1140 patients
      (5818.9 patient-years) were analysed and no patient were lost to follow-up.
      Median follow-up was 4.3 years (range 0.2-12.8 years). Median age at the time of
      training was 54.2 years (range 18.2-85.2) and 34.6% were women. All-cause
      mortality was 1.4 per 100 patient-years (95% CI 1.1-1.7) with a higher rate in
      patients with atrial fibrillation (2.5; 1.6-3.7; p<0.001), patients>50 years of
      age (2.0; 1.6-2.6; p<0.001), and men (1.6; 1.2-2.1; p = 0.036). The rate of
      thromboembolic events was 0.4 (0.2-0.6) and independent from indications, sex and
      age. Major bleeding were observed in 1.1 (0.9-1.5) per 100 patient-years.
      Efficacy was comparable to standard care and new oral anticoagulants in a network
      meta-analysis. PSM of properly trained patients is effective and safe in a long
      term real-life setting and robust across clinical subgroups. Adoption in various
      clinical settings, including those with limited access to medical care or rural
      areas is warranted. 

PMID- 24748063
TI  - Pai syndrome: challenging prenatal diagnosis and management.
AB  - Pai syndrome is a rare disorder that includes midline cleft lip, pericallosal
      lipoma and cutaneous polyp of the face. We report a case of prenatal diagnosis
      using sonography and MRI. We emphasize the importance of facial examination with
      prenatal association of midline cleft lip and pericallosal lipoma in making the
      diagnosis of Pai syndrome. 

PMID- 24748064
TI  - Intraoperative blood loss during decompressive craniectomy for intractable
      intracranial hypertension after severe traumatic brain injury in children.
AB  - PURPOSE: There are no data available on the risk of intraoperative bleeding
      during decompressive craniectomy (DC) after traumatic brain injury (TBI) in
      children. The objectives of this study were to assess the risk of intraoperative
      bleeding during DC for intractable intracranial hypertension after TBI, to
      identify potential factors associated with the risk of bleeding during DC, and to
      assess the impact of DC on systemic and cerebral hemodynamics and on coagulation.
      METHODS: Twelve children were identified as having undergone DC after TBI from
      April 2009 to June 2013 in our center. Subjects were allocated into two groups
      according to the percentage of blood loss (IBL) during the intraoperative period
      (<or >=50 % of the estimated blood volume (EBV)). RESULTS: The median IBL during
      DC was 49 [17-349] % of the EBV. Children with an IBL >= 50 % of EBV had higher
      preoperative intracranial pressure (ICP) (p = 0.03) and international normalized
      ratio (INR) (p = 0.02) than those with an IBL < 50 % of EBV. DC induced
      significant decreases in ICP (p = 0.0005), mean arterial pressure (p = 0.01), and
      a significant increase in norepinephrine flow rate (p = 0.04) between the
      immediate pre- and postoperative periods. CONCLUSIONS: DC allows a significant
      decrease in ICP after severe pediatric TBI but is a surgical procedure at a high
      risk of bleeding. High ICP and INR during the immediate preoperative period are
      the main factors associated with increased IBL during DC. Further studies are
      needed to confirm our results and to assess the impact of the amount of IBL on
      the postoperative survival and functional outcome.

PMID- 24748065
TI  - Role of the VEGF 936 gene polymorphism and VEGF-A levels in the late-term
      arteriovenous fistula thrombosis in patients undergoing hemodialysis.
AB  - PURPOSE: Vascular access is vital for hemodialysis patients. A major factor that
      facilitates arteriovenous (AV) fistula failure is stenosis and thrombosis due to
      intimal hyperplasia developing in the venous segment of AV fistula. It has been
      reported that VEGF accelerated re-endothelialization, reduction in intimal
      thickening, and/or mural thrombus formed in the injured vascular structures. In
      this study, we aimed to identify the effect of the VEGF 936 gene polymorphism and
      vascular endothelial growth factor-A (VEGF-A) levels in the late period of AV
      fistula loss in hemodialysis patients. METHODS: The study was carried out with a
      patient group of 42 individuals who experienced two or more fistula thrombosis in
      the late period after the AV fistula operation and also a control group of 38
      patients who have not had any AV fistula thrombosis history for 3 years or more.
      All participants were assessed for VEGF-936C/T gene polymorphism and VEGF-A
      levels. RESULTS: VEGF-936C/T genotypes were determined in the large proportion in
      the control group (31.6 %), while VEGF-936C/C genotypes were determined in a
      large proportion in the patient group (90.5 %). Individuals carrying the VEGF
      936C/C genotype had an increased risk of 5.54 for getting AV fistula thrombosis.
      The VEGF-A levels of patient group (27.3 +/- 43.5 pg/ml) were significantly lower
      than those of the control group (70.7 +/- 53.1 pg/ml). CONCLUSION: There is an
      increased risk of AV fistula thrombosis in individuals carrying the VEGF-936C/C
      genotype. The other renal replacement modalities should be considered in patients
      with this genotype. As a result, it will be possible to prevent the morbidity and
      mortality due to fistula failure.

PMID- 24748066
TI  - Expression response of duplicated metallothionein 3 gene to copper stress in
      Silene vulgaris ecotypes.
AB  - Metallothioneins (MTs) were identified as important players in metal metabolism.
      MT3 gene presents a key metallothionein controlling copper homeostasis in plants.
      We have selected one cupricolous and one non-cupricolous ecotype to isolate and
      analyse the MT3 gene in Silene vulgaris. For expression data comparison, we have
      also included other metal-tolerant ecotypes. Based on a S. vulgaris BAC library
      screening, we have identified and sequenced a genomic clone containing MT3 gene
      (SvMT3). We found that SvMT3 gene has been locally duplicated in a tandem
      arrangement. Expression analysis and complementation studies using yeast mutants
      showed that both copies of the SvMT3 gene were functional. Moreover, we examined
      the expression of MT3 gene(s) in selected ecotypes under different copper
      treatments to show the tissue-specific expression response to copper stress. We
      demonstrated that higher copper concentrations specifically affected MT3
      expression among ecotypes. Our analysis shows that MT3a has similar expression
      pattern in cupricolous ecotypes while MT3b has common expression features shared
      by all metallophyte S. vulgaris ecotypes. Our data indicate that down-regulation
      of MT3b root expression in higher copper concentrations is associated with copper
      stress. We propose that there might be a specific regulation of SvMT3s
      transcription depending on the type of heavy metal tolerance.

PMID- 24748068
TI  - Patient safety in the era of healthcare reform.

PMID- 24748069
TI  - Minimally invasive versus open posterior lumbar interbody fusion: a systematic
      review.
AB  - BACKGROUND: Although conventional open posterior lumbar interbody fusion (open
      PLIF) is efficacious in management of lumbar spinal instability, concerns exist
      regarding lengthy hospital stays, blood loss, and postoperative complications.
      Minimally invasive posterior lumbar interbody fusion (MIS PLIF) may be able to
      address these concerns, but the research on this topic has not been
      systematically reviewed. QUESTIONS/PURPOSES: We performed a systematic review to
      determine whether MIS PLIF or open PLIF results in (1) better perioperative
      parameters, including blood loss, operative times, and length of hospital stay;
      (2) improved patient-reported outcome scores; and (3) improved disc distraction
      and (4) frequency of reoperation and complications when compared with open PLIF
      procedures. METHODS: A literature search of the MEDLINE database identified seven
      studies that met our inclusion criteria. A total of seven articles were included;
      quality was assessed using the Methodological Index for Non-Randomised Studies
      (MINORS) scale. Descriptive statistics were used to describe the included
      articles. RESULTS: In most studies, MIS PLIF was associated with decreased blood
      loss and shorter hospital stay but longer operative times. MIS PLIF resulted in
      better patient-related outcomes when compared with open PLIF in two studies in
      the short term, but most of the studies in this review found no short-term
      differences, and there was no difference at long-term followup in any studies.
      There was no significant difference in disc distraction. Both techniques appeared
      to have similar complication rates and reoperation rates. CONCLUSIONS: Based on
      the available evidence, which we restricted to prospective and retrospective
      studies with control groups, but did not include any well-designed randomized
      trials, MIS PLIF might lead to better perioperative parameters, but there was
      little evidence for improved patient-reported outcomes in the MIS groups.
      Randomized controlled trials are needed to compare these two surgical techniques.

PMID- 24748070
TI  - Do patients with ewing's sarcoma continue with sports activities after limb
      salvage surgery of the lower extremity?
AB  - BACKGROUND: Limb salvage surgery has evolved to become the standard method of
      treating sarcomas of the extremities with acceptable oncologic results. However,
      little information exists relative to the activity level or ability to
      participate in sports after tumor reconstructions. QUESTIONS/PURPOSES: The aims
      of the study were to answer the following questions: (1) Which sports activity
      levels and what types of sports can be expected in the long term after tumor
      reconstruction? (2) Which frequency durations are patients with Ewing's sarcoma
      able to perform in long-term followup after local control? (3) Do surgical
      complications affect sports activity level? METHODS: Thirty patients (13 females,
      17 males; mean age, 18 +/- 8 years; range, 2-36 years at diagnosis; mean followup
      16 +/- 6 years [minimum, 5 years]) were included. Tumors were located in the
      pelvis, femur, tibia, and fibula. Surgical procedures included surgical
      resections alone (n = 8), surgical resection with biological reconstruction (n =
      9), or endoprosthetic reconstruction (n = 13). We assessed UCLA sports activity
      levels, kinds of sports as well as the frequency per week and the duration of
      each training unit at long term (minimum followup, 5 years). RESULTS: In long
      term followup 83% patients (25 of 30) were performing athletic activity
      regularly. The hours/week of sports depended on type of surgery and were highest
      after resections in the pelvis and femur (5.8) and were lowest after
      megaprosthetic reconstruction of the pelvis (1.0). Patients undergoing biologic
      reconstructions were able to perform high-impact sports. UCLA sports activity
      levels were high after joint-preserving vascularized fibula for tibia
      reconstruction (7.4) and after megaprosthetic reconstruction of the lower
      extremity (6.3-6.4) and were low after tumors located in the fibula (4.2).
      Complications during followup did not significantly influence sports activity in
      long-term survivors. CONCLUSIONS: Long-term survivors can achieve high levels of
      sports activity in many instances. Tumor sites are associated with the
      postoperative sports activity levels. This information can help surgeons counsel
      patients in terms of athletic expectations after limb salvage reconstruction for
      patients with Ewing's sarcoma. LEVEL OF EVIDENCE: Level III, therapeutic study.
      See Guidelines for Authors for a complete description of levels of evidence.

PMID- 24748071
TI  - Editor's spotlight/take 5: diagnosing periprosthetic joint infection: has the era
      of the biomarker arrived?

PMID- 24748073
TI  - A surgical approach algorithm for transverse posterior wall fractures aids in
      reduction quality.
AB  - BACKGROUND: Transverse posterior wall fractures are difficult to treat and
      historically have been associated with stiffness, posttraumatic arthritis, and
      pain, which correlate with the reduction. The Kocher-Langenbeck approach is used
      most often, whereas the extended iliofemoral approach has been reserved for more
      complex injury patterns. The latter approach has substantially more risks. No
      data to our knowledge exist on the use of sequential anterior and posterior
      approaches for this pattern. QUESTIONS/PURPOSES: The purpose of this study is to
      evaluate an algorithmic method to determine the choice of surgical approach(es)
      for transverse posterior wall fractures. The main question is: will this approach
      based algorithm allow for adequate reduction and stabilization to union? Our
      secondary endpoints were Merle d'Aubigne scores, reoperations, and radiographic
      sequelae including arthritis, avascular necrosis, and heterotopic ossification.
      METHODS: A retrospective study was conducted in which patients were drawn from an
      existing database. The inclusion criterion was transverse posterior wall
      fractures with adequate imaging treated by one surgeon. All but one patient were
      treated within 2 weeks of injury. Mean followup was 23 months (range, 3 months to
      11 years). Between November 5, 1999, and August 22, 2012, 74 patients were
      treated with open reduction internal fixation for this injury; nine were excluded
      as a result of percutaneous treatment or inadequate preoperative imaging. The
      remaining 65 patients (88%) comprised the study group. All patients were treated
      by the senior surgeon with an algorithm that consisted of either a Kocher
      Langenbeck or sequential approach based on the location, magnitude, and direction
      of displacement of the ischiopubic segment. Indomethacin was prescribed to all
      patients for heterotopic ossification prophylaxis for a total of 6 weeks
      postoperatively. Based on the algorithm, 82% (53 patients) were treated with
      Kocher-Langenbeck and 18% (12 patients) with the sequential approach. Adequacy of
      reduction was measured using AP and Judet views of the pelvis; union was
      determined empirically by pain-free weightbearing and lack of displacement over
      time. Outcomes were the Merle d'Aubigne score and radiographic findings of
      avascular necrosis or arthrosis. RESULTS: The algorithm resulted in 100%
      reduction within 1 mm on plain radiographs. Initial displacement was greater in
      the patients undergoing the sequential approach (p=0.01, 7.7 versus 12.4 mm). The
      average d'Aubigne score was 15.3. Radiographic arthritis scores were 68%
      excellent/good. Avascular necrosis developed in five patients (8%). Five patients
      (8%) went on to THA, and four patients (6%) developed superficial or deep
      infection. Only one patient developed Brooker III heterotopic ossification and
      this was not symptomatic. CONCLUSIONS: This algorithm helps guide appropriate
      selection of the surgical approach and results in accurate reduction with
      functional and radiographic results that are comparable with existing series
      while avoiding extended approaches. However, like any operative decision, the
      choice of approach should not depend entirely on an algorithm; rather, the
      algorithm is best used as a guide to understand the factors involved in treating
      these rare and complex injuries and to help make an appropriate choice for an
      individual patient. LEVEL OF EVIDENCE: Level IV, case series. See the Guidelines
      for Authors for a complete description of levels of evidence.

PMID- 24748074
TI  - Cancellation of cellular responses to nanoelectroporation by reversing the
      stimulus polarity.
AB  - Nanoelectroporation of biomembranes is an effect of high-voltage, nanosecond
      duration electric pulses (nsEP). It occurs both in the plasma membrane and inside
      the cell, and nanoporated membranes are distinguished by ion-selective and
      potential-sensitive permeability. Here we report a novel phenomenon of bioeffects
      cancellation that puts nsEP cardinally apart from the conventional
      electroporation and electrostimulation by milli- and microsecond pulses. We
      compared the effects of 60- and 300-ns monopolar, nearly rectangular nsEP on
      intracellular Ca(2+) mobilization and cell survival with those of bipolar 60 + 60
      and 300 + 300 ns pulses. For diverse endpoints, exposure conditions, pulse
      numbers (1-60), and amplitudes (15-60 kV/cm), the addition of the second phase
      cancelled the effects of the first phase. The overall effect of bipolar pulses
      was profoundly reduced, despite delivering twofold more energy. Cancellation also
      took place when two phases were separated into two independent nsEP of opposite
      polarities; it gradually tapered out as the interval between two nsEP increased,
      but was still present even at a 10-us interval. The phenomenon of cancellation is
      unique for nsEP and has not been predicted by the equivalent circuit, transport
      lattice, and molecular dynamics models of electroporation. The existing paradigms
      of membrane permeabilization by nsEP will need to be modified. Here we discuss
      the possible involvement of the assisted membrane discharge, two-step oxidation
      of membrane phospholipids, and reverse transmembrane ion transport mechanisms.
      Cancellation impacts nsEP applications in cancer therapy, electrostimulation, and
      biotechnology, and provides new insights into effects of more complex waveforms,
      including pulsed electromagnetic emissions. 

PMID- 24748075
TI  - Cloning and expression analyses of the anthocyanin biosynthetic genes in mulberry
      plants.
AB  - Anthocyanins are natural food colorants produced by plants that play important
      roles in their growth and development. Mulberry fruits are rich in anthocyanins,
      which are the most important active components of mulberry and have many
      potentially beneficial effects on human health. The study of anthocyanin
      biosynthesis will bring benefits for quality improvement and industrial
      exploration of mulberry fruits. In the present study, nine putative genes
      involved in anthocyanin biosynthesis in mulberry plants were identified and
      cloned. Sequence analysis revealed that the mulberry anthocyanin biosynthetic
      genes were conserved and had counterparts in other plants. Spatial
      transcriptional analysis showed detectable expression of eight of these genes in
      different tissues. The results of expression and UPLC analyses in two mulberry
      cultivars with differently colored fruit indicated that anthocyanin
      concentrations correlated with the expression levels of genes associated with
      anthocyanin biosynthesis including CHS1, CHI, F3H1, F3'H1, and ANS during the
      fruit ripening process. The present studies provide insight into anthocyanin
      biosynthesis in mulberry plants and may facilitate genetic engineering for
      improvement of the anthocyanin content in mulberry fruit. 

PMID- 24748076
TI  - Prostate Cancer Prognostic Factors Among Asian Patients Born in the US Compared
      to Those Born Abroad.
AB  - US surveillance data indicate that incidence of prostate cancer differs by place
      of birth among Asian men. However, it is less clear if the prognostic factors for
      prostate cancer also differ by place of birth. The study included 7,824 Asian
      prostate cancer patients diagnosed between 2004 and 2009 and reported to the
      Surveillance Epidemiology and End Results (SEER) program. Logistic regression
      models were used to evaluate the relation of place of birth (foreign born vs. US
      born) to three outcomes: prostate specific antigen (PSA) level, Gleason score,
      and T classification, adjusting for age, marital status, Rural-Urban Continuum
      Code, and SEER registry. All outcome variables were binary using different
      cutoffs: >= 4, >= 10 and >= 20 ng/ml for PSA; >= 7 and >= 8 for Gleason score;
      and >= T2 and >= T3 for T classification. Elevated PSA was more common among
      foreign born Asian men regardless of the cut point used. In the analysis
      comparing foreign born versus US born patients by ethnic group, the association
      with PSA was most pronounced at cut point of >= 20 ng/ml for Chinese men (OR
      1.68, 95% CI 1.02-2.75), and at cut point of >= 4 ng/ml for Japanese men (OR
      2.73, 95% CI 1.20-6.21). A statistically significant association with Gleason
      score was only found for Japanese men and only for the cutoff >= 7 (OR 1.71, 95%
      CI 1.12-2.61). There was no difference in clinical T classification between
      foreign-born and US-born Asian men. Inclusion of cases with missing place of
      birth or restriction of data to those who underwent radical prostatectomy did not
      substantially change the results. The data suggest that foreign-born Asian
      prostate cancer patients may have moderately elevated PSA levels at diagnosis
      compared with their US born counterparts. For the other prognostic markers, the
      associations were less consistent and did not form a discernible pattern.

PMID- 24748077
TI  - Callous-unemotional traits and the treatment of conduct problems in childhood and
      adolescence: a comprehensive review.
AB  - The treatment of conduct problems among children and adolescents with callous
      unemotional (CU) traits has been subject to much speculation; however, treatment
      outcome research has been surprisingly limited and findings have been mixed. This
      review examines the research to date in this field as it pertains to two key
      questions. First, are CU traits associated with clinical outcomes and processes
      in the family based treatment of child and adolescent conduct problems? Second,
      can family based intervention produce change in CU traits? Using a systematic
      search strategy, we identified 16 treatment outcomes studies that can be brought
      to bear on these questions. These studies provide strong evidence of unique
      associations between CU traits and risk for poor treatment outcomes, while at the
      same time indicating that social-learning-based parent training is capable of
      producing lasting improvement in CU traits, particularly when delivered early in
      childhood. We discuss the potential for this emerging evidence base to inform the
      planning and delivery of treatments for clinic-referred children with CU traits,
      and detail an ongoing program of translational research into the development of
      novel interventions for this high-risk subgroup. 

PMID- 24748079
TI  - [Recent progress in studies of the somatosensory cortex].
AB  - I reviewed recent studies on the somatosensory cortices, both neurophysiological
      studies in animals and studies on humans using neuroimaging techniques. The
      topics reviewed include 1) hierarchical information processing in the digit
      region of the somatosensory cortex, 2) integration of information from both sides
      of the body, 3) influence of vision on somatosensory activity, and 4) pain and
      somatosensory cortex. Functional implications of new findings were discussed.

PMID- 24748078
TI  - Impact of miRNA sequence on miRNA expression and correlation between miRNA
      expression and cell cycle regulation in breast cancer cells.
AB  - The miRNAs regulate cell functions by inhibiting expression of proteins. Research
      on miRNAs had usually focused on identifying targets by base pairing between
      miRNAs and their targets. Instead of identifying targets, this paper proposed an
      innovative approach, namely impact significance analysis, to study the
      correlation between mature sequence, expression across patient samples or time
      and global function on cell cycle signaling of miRNAs. With three distinct types
      of data: The Cancer Genome Atlas miRNA expression data for 354 human breast
      cancer specimens, microarray of 266 miRNAs in mouse Embryonic Stem cells (ESCs),
      and Reverse Phase Protein Array (RPPA) transfected by 776 miRNAs in MDA-MB-231
      cell line, we linked the expression and function of miRNAs by their mature
      sequence and discovered systematically that the similarity of miRNA expression
      enhances the similarity of miRNA function, which indicates the miRNA expression
      can be used as a supplementary factor to predict miRNA function. The results also
      show that both seed region and 3' portion are associated with miRNA expression
      levels across human breast cancer specimens and in ESCs; miRNAs with similar seed
      tend to have similar 3' portion. And we discussed that the impact of 3' portion,
      including nucleotides 13-16, is not significant for miRNA function. These results
      provide novel insights to understand the correlation between miRNA sequence,
      expression and function. They can be applied to improve the prediction algorithm
      and the impact significance analysis can also be implemented to similar analysis
      for other small RNAs such as siRNAs.

PMID- 24748080
TI  - [Temporal and spatial representations of tactile sensation].
AB  - How does the brain encode "when" and "where" events that have occurred during
      tactile sensory processing? The simplest protocol to address this question would
      be asking participants to judge the temporal order of tactile stimuli delivered
      to both hands while varying their spatial relationship. In this review, I will
      focus on the illusion that the subjective temporal order of two tactile stimuli
      (one delivered to each hand) is reversed when the arms are crossed. By
      introducing recent findings related to this illusion, I will discuss how the
      temporal and spatial representations of tactile sensation interact with each
      other, and propose neural mechanisms potentially underlying this interaction.

PMID- 24748081
TI  - [Corpus callosum and somesthetic transfer].
AB  - Here we describe somesthetic disconnection in 3 patients with callosal lesions.
      The results suggest the importance of the anterior and/or dorsal part of the
      posterior truncus of the corpus callosum for interhemispheric transfer of
      discriminative sensations and integrated somesthetic information necessary to
      tactile naming and somesthetic reading. We provide a hypothesis for the neural
      mechanisms underlying somesthetic communication.

PMID- 24748082
TI  - [Disorders of body schema].
AB  - A variety of disorders have been associated with the concept of body schema.
      However, this concept has been interpreted in many ways, and there is no
      consensus on the nature and cognitive mechanisms of body schema. Historically,
      two major issues have been discussed. One was the body-specificity of the body
      schema, and the other was the relationship between input and output modality.
      Autotopagnosia, an inability to localize and orient different parts of the body,
      has been a focus of attention because it is thought to provide insight into the
      function of body schema. Although there have not been many cases of pure
      autotopagnosia, a double dissociation indicating the independence of body
      specific system. There are a few working hypotheses for cognitive models of body
      schema, which can explain the different types of autotopagnosia. One model
      includes multiple representation subsystems for body processing, while another
      assumes the use of intrinsic and extrinsic egocentric coordinates to maintain on
      line processing for body state. The consistency of these accounts should be
      examined in light of extensive neuroimaging and psychological data, to construct
      a plausible model for body schema.

PMID- 24748083
TI  - [Aberrant bodily self in schizophrenia].
AB  - Patients with schizophrenia often experience aberrant bodily self including
      depersonalization and cenesthopathy, especially in its prodromal and early stage.
      These symptoms are regarded as the beginning of self-disturbances (i.e. the core
      psychopathology of the illness). Thus, an understanding of schizophrenic bodily
      experiences could provide insight into the pathophysiology of schizophrenia.
      Recently, in the field of cognitive neuroscience, research on self-awareness
      during intentional actions has focused on examining sense of body ownership (SoO)
      and sense of agency (SoA). The most critical factor for the emergence of those
      higher-order senses of self is subject's intention for actions. Intentional
      signals could integrate multiple bodily sensory feedbacks during actions, and
      lead to develop a coherent sense of self. Empirical studies using behavioral and
      neuroimaging experiments have demonstrated that schizophrenic patients exhibit
      specific patterns of abnormal SoO and SoA. Thus, from a clinical standpoint, the
      detection of specific nature of schizophrenic bodily experiences could provide
      evidence for early diagnosis and intervention for schizophrenia.

PMID- 24748084
TI  - [Neural representation of human body schema and corporeal self-consciousness].
AB  - The human brain processes every sensation evoked by altered posture and builds up
      a constantly changing postural model of the body. This is called a body schema,
      and somatic signals originating from skeletal muscles and joints, i.e.
      proprioceptive signals, largely contribute its formation. Recent neuroimaging
      techniques have revealed neuronal substrates for human body schema. A dynamic
      limb position model seems to be computed in the central motor network
      (represented by the primary motor cortex). Here, proprioceptive (kinesthetic)
      signals from muscle spindles are transformed into motor commands, which may
      underlie somatic perception of limb movement and facilitate its efficient motor
      control. Somatic signals originating from different body parts are integrated in
      the course of hierarchical somatosensory processing, and activity in higher-order
      somatosensory parietal cortices is capable of representing a postural model of
      the entire body. The left fronto-parietal network associates internal motor
      representation with external object representation, allowing the embodiment of
      external objects. In contrast, the right fronto-parietal regions connected by the
      most inferior branch of superior longitudinal fasciculus fibers seem to have the
      functions of monitoring bodily states and updating body schema. We hypothesize
      that activity in these right-sided fronto-parietal regions is deeply involved in
      corporeal self-consciousness.

PMID- 24748085
TI  - [Vision].
AB  - The existence of two visual information pathways has gained acceptance, and the
      entire scheme of visual information processing has been understood. The visual
      cortex has been subdivided into areas, whose neurophysiological properties have
      been examined in the monkey. Our understanding of the visual processing system
      has been built by information earned in parts. However, despite knowledge about
      the complete process, the associations between the individual components remain
      to be understood. In addition, elucidating the neural basis of perception
      experienced in daily living would be a challenge in the future.

PMID- 24748086
TI  - [Visual attention and its control mechanisms].
AB  - Given the vast amount of visual information in visual scenes, the capacity of our
      brain to processes such scenes is severely limited. The core mechanism of
      selection is referred to as visual attention, and it has been the topic of
      intense investigation for over 25 years in experimental psychology and cognitive
      neuroscience. Visual attention is not a single, unitary mechanism, but consists
      of multiple subcomponents. Attention can be directed to various aspects of visual
      information, such as spatial location, features, or objects. Additionally,
      attention is guided by external factors such as the salience of stimuli, or
      whether we are able to move our attention volitionally. The purpose of this
      article is to review the status of these components of attentional guidance and
      how they interact with each other, with an emphasis on psychophysical studies.

PMID- 24748087
TI  - [Prosopagnosia and facial expression recognition].
AB  - This paper reviews clinical neuropsychological studies that have indicated that
      the recognition of a person's identity and the recognition of facial expressions
      are processed by different cortical and subcortical areas of the brain. The
      fusiform gyrus, especially the right fusiform gyrus, plays an important role in
      the recognition of identity. The superior temporal sulcus, amygdala, and medial
      frontal cortex play important roles in facial-expression recognition. Both facial
      recognition and facial-expression recognition are highly intellectual processes
      that involve several regions of the brain.

PMID- 24748088
TI  - [Congenital prosopagnosia: symptoms, cognition, and neural correlates].
AB  - Congenital prosopagnosia (CP) refers to lifelong and severe impairment of face
      processing, which is apparent from birth, despite intact visual and intellectual
      abilities. Usually, individuals with CP do not exhibit brain lesions or
      neurological disorders that account for their specific impairment. An
      epidemiological survey revealed that the prevalence rate of CP was approximately
      2.5% in a young Caucasian population. CP frequently runs in families, suggesting
      a genetic component in this disturbance. Detailed neuropsychological
      investigations demonstrated that individuals with CP show reduced performance in
      face tasks including famous face recognition, face matching, and
      encoding/retrieval of novel faces. In contrast, they can judge facial expression
      and eye gaze almost as well as healthy controls. These results suggest an
      impairment of holistic processing of faces in individuals with CP.
      Neurophysiological investigation using ERP showed that individuals with CP, as a
      group, had reduced voltage of the N170 component, which is a hallmark of face
      processing in the temporal lobe. However, there were large variations in the
      results of N170 among individuals with CP. Structural MRI showed that the
      impairments could be due to reduced volume of grey matter and microstructure of
      white matter in a part of the temporal lobe. Studies using fMRI and face tasks
      revealed mixed results with regard to face-selective activation in the fusiform
      gyrus. These findings indicate the heterogeneity of CP, and further investigation
      is needed to clarify neurodevelopmental substrates of face processing. Results
      from normative data obtained using the Japanese version of a questionnaire for
      screening of hereditary prosopagnosia is presented.

PMID- 24748089
TI  - [Action].
AB  - In recent years, the mechanisms related to decision-making in the brain have been
      proposed and studied. The neural mechanisms involved in the selection of an
      action prior to its execution are becoming evident, particularly in relation to
      the frontal lobe. Nevertheless, the fundamental neural mechanisms of movement
      remain unknown, although it is generally accepted that these actions are
      controlled by higher-order motor areas in the brain. Movement is the result of a
      series of timed contractions of various muscle groups; however, elucidating the
      underlying neural basis of this temporal control would be a challenge in the
      future.

PMID- 24748090
TI  - [Functions of the insula and sense of self].
AB  - As symbolically represented by the rubber hand illusion, the sense of body
      ownership is constructed by the integration of multisensory signals. Due to its
      strategic location as an interface between the brain and body, the insula, as
      well as the temporal-parietal junction and premotor area, have been thought to
      play an important role in multisensory integration. The insula, especially its
      most anterior portion, is also a site for representation and awareness of
      interoception: sensing the internal physiological states of the body. Recent
      studies have showed that interoception can be integrated with exteroception, such
      as vision and touch, and can thus contribute to the sense of body-ownership.
      Here, recent empirical findings and a hypothetical model about functions of the
      insula for the sense of body-ownership are introduced. Furthermore, I will try to
      expand the model to explain the significance of interoception in decision-making.

PMID- 24748091
TI  - [Motor memories formed by redundant neural representation].
AB  - Previous studies have tried to elucidate how kinematics of movement is uniquely
      represented in the brain. Considering the large number of neurons in the brain,
      however, it is possible that an identical movement is represented by distinct
      patterns of neural activity in the brain. Here, I first discuss the possible
      relationship between the neural representation and motor memory. Subsequently, I
      introduce several experimental examples from my laboratory showing that the
      redundancy of neural representations of movements might be reflected in the
      ability of the brain to switch flexibly between distinct motor memories (or
      internal models) for a physically identical movement depending on different
      behavioral contexts. I also demonstrate that the ability for forming and
      retrieving different sets of motor memories plays a functional role in motor
      control.

PMID- 24748092
TI  - [Neural mechanisms underlying visually guided action].
AB  - Visually guided action is generated via multiple modes of information processing.
      Here, we discuss three modes of neural processing underlying visually guided
      action. The first mode involves direct visuo-action association. In this mode, an
      action is planned to reach and grasp a target based on information about the
      target position (for reaching) and shape (for grasping). The network connecting
      the premotor and parietal cortices plays a central role in this mode. The second
      mode involves conditional visuo-action association. In this mode, a particular
      action is selected based on a rule associating a visual feature with an action.
      The third mode involves conditional visuo-goal association. In this mode, a
      visual signal is associated with a behavioral goal, but not with an action. A
      particular action is subsequently selected to meet this goal. Areas on the route
      from the inferotemporal cortex to the dorsal premotor cortex, such as the
      prefrontal cortex and basal ganglia, play a role in achieving conditional visuo
      action and conditional visuo-goal associations. In summary, our analysis suggests
      the involvement of multiple brain networks converging on the premotor cortex in
      the three modes of neural processing utilized for generating visually guided
      action.

PMID- 24748093
TI  - [Functional coupling of the frontal and parietal lobes in action].
AB  - Apraxia is the inability to perform actions or move different parts of the body
      in the intended manner, despite normal physical capability of movement. Based on
      his studies, Liepmann divided apraxia into three types: ideational apraxia,
      ideomotor apraxia, and limb-kinetic apraxia. Clinical findings such as ideomotor
      apraxia in Broca's area and apraxia in patients with Parkinson's disease (PD) and
      parietal ataxia suggest sensorimotor integration and action control in the
      parietofrontal circuits. Based on studies of the mirror neuron system, disorders
      in gesture production could be associated with disorders of gesture
      understanding. We recently reported ideomotor apraxia in association with lesions
      in Broca's area. Broca's area is the center of speech production, and also
      mediates action production. Although apraxia is not a typical clinical feature of
      PD, varying degrees of apraxia have been reported. The dysfunction of the motor
      and premotor areas, which send projections to the basal ganglia, causes this
      apraxia. Parietal ataxia is caused by lesions in the parietal lobe, which are
      thought to be caused by disconnection between the cerebellum and Brodmann area 5
      in the parietal lobe.

PMID- 24748094
TI  - [Exploring dream contents by neuroimaging].
AB  - Dreaming is a subjective experience during sleep that is often accompanied by
      vivid perceptual and emotional contents. Because of its fundamentally subjective
      nature, the objective study of dream contents has been challenging. However,
      since the discovery of rapid eye movements during sleep, scientific knowledge on
      the relationship between dreaming and physiological measures including brain
      activity has accumulated. Recent advances in neuroimaging analysis methods have
      made it possible to uncover direct links between specific dream contents and
      brain activity patterns. In this review, we first give a historical overview on
      dream researches with a focus on the neurophysiological and behavioral signatures
      of dreaming. We then discuss our recent study in which visual dream contents were
      predicted, or decoded, from brain activity during sleep onset periods using
      machine learning-based pattern recognition of functional MRI data. We suggest
      that advanced analytical tools combined with neural and behavioral databases will
      reveal the relevance of spontaneous brain activity during sleep to waking
      experiences.

PMID- 24748095
TI  - [The significance of oxidized DJ-1 protein (oxDJ-1) as a biomarker for
      Parkinson's disease].
AB  - The search for biomarkers of Parkinson's disease (PD) typically focuses on
      cerebrospinal fluid components, with very few reports on simple biomarkers
      identifiable by blood analysis. In this report, we determined the level of
      oxidized DJ-1 protein (oxDJ-1) in red blood cells by ELISA and examined the
      association with MIBG myocardial scintigraphy. Levels of oxDJ-1 were higher in
      unmedicated patients with PD (142.2 +/- 21.8 ng oxDJ-1/mg protein; n = 13)
      compared to the L-DOPA-treated group (85.6 +/- 10.1 ng oxDJ-1/mg protein; n = 10)
      and controls (56.0 +/- 6.2 ng oxDJ-1/mg protein; n = 17), thereby showing
      significant intergroup differences. Intervention with L-DOPA showed a tendency to
      decrease oxDJ-1 levels in patients. The diagnostic sensitivity of oxDJ-1
      measurement was 87% and that of simultaneously conducted MIBG scintigraphy was
      89%; this showed that the diagnostic sensitivity was comparable. Our results
      showed that measurement of oxDJ-1 levels in red blood cells can be useful and
      oxDJ-1 can be used as a biomarker for the early diagnosis of PD. (Receieved July
      31, 2013; Accepted October 16, 2013; Published April 1, 2014).

PMID- 24748096
TI  - Communication about symptoms and quality of life issues in patients with cancer:
      provider perceptions.
AB  - This study used qualitative data collection and analysis methods to describe
      provider perceptions of addressing patient-initiated communication about common
      or sensitive symptom and quality of life issues (SQIs) in oncology. Eligible
      participants were health care providers who had participated in a larger trial
      testing a patient-centered technology to assess cancer SQIs and support self
      care. Audio-recorded vignettes were simulated based on recorded clinic visits
      from the larger trial and presented during semi-structured cognitive interviews
      with each participant. Transcripts of the interviews were content analyzed.
      Twelve providers participated. Participants' responses included four themes: the
      institutional and clinical context, the complexity of addressing SQIs, strategies
      used to understand SQIs, and creating a plan to address SQIs. Participants felt
      that approaching SQIs inside and outside of the clinic required ongoing
      communication within a multidisciplinary team both to gather information and
      manage the SQI. Forming a relationship with the patient was one strategy to
      facilitate assessing SQIs. Most participants expressed a need for guidance about
      effective SQI communication. Providers perceived approaching SQIs as a routine
      part of interdisciplinary clinical care. The specific symptom and the complexity
      of its management influenced the process of assessing and managing SQIs. Findings
      have implications for institutional processes, training, evaluation, and program
      development. 

PMID- 24748097
TI  - Understanding the patient-provider communication needs and experiences of Latina
      and non-Latina White women following an abnormal mammogram.
AB  - Latinas are more likely to delay recommended follow-up care than non-Latina White
      (NLW) women after an abnormal mammogram result. Ethnic differences in
      communication needs and experiences with health-care staff and providers may
      contribute to these delays as well as satisfaction with care. Nonetheless, little
      research has explored the aspects of communication that may contribute to patient
      comprehension, adherence to follow-up care, and satisfaction across ethnicity.
      The purpose of this exploratory, qualitative study was to identify patients'
      communication needs and experiences with follow-up care among Latina and NLW
      women who received an abnormal mammogram. We conducted 41 semi-structured
      interviews with 19 Latina and 22 NLW women between the ages of 40 and 74 who had
      received an abnormal mammogram. Communication themes indicated that women's needs
      and experiences concerning abnormal mammograms and follow-up care varied across
      ethnicity. Latinas and NLW women appeared to differ in their comprehension of
      abnormal results and follow-up care as a result of language barriers and health
      literacy. Both groups of women identified clear, empathic communication as being
      important in patient-provider communication; however, Latinas underscored the
      need for warm communicative styles, and NLW women emphasized the importance of
      providing more information. Women with high levels of satisfaction with patient
      provider interactions appeared to have positive perspectives of subsequent
      screening and cancer treatment. To improve patient satisfaction and adherence to
      follow-up care among Latinas, educational programs are necessary to counsel
      health-care professionals with regard to language, health literacy, and empathic
      communication needs in health-care service delivery. 

PMID- 24748098
TI  - An isotope-dilution, GC-MS assay for formate and its application to human and
      animal metabolism.
AB  - Formate, a crucial component of one-carbon metabolism, is increasingly recognized
      as an important intermediate in production and transport of one-carbon units.
      Unlike tetrahydrofolate-linked intermediates, it is not restricted to the
      intracellular milieu so that circulating levels of formate can provide insight
      into cellular events. We report a novel isotope-dilution, GC-MS assay employing
      derivatization by 2,3,4,5,6-pentafluorobenzyl bromide for the determination of
      formate in biological samples. This assay is robust and sensitive; it may be
      applied to the measurement of formate in serum, plasma and urine. We demonstrate
      how this method may be applied by providing the first characterization of formate
      levels in a human population; formate levels were higher in males than in
      females. We also show how this procedure may be applied for the measurement of in
      vivo kinetics of endogenous formate production in experimental animals. 

PMID- 24748099
TI  - Biological and surface-active properties of double-chain cationic amino acid
      based surfactants.
AB  - Cationic amino acid-based surfactants were synthesized via solid phase peptide
      synthesis and terminal acylation of their alpha and epsilon positions with
      saturated fatty acids. Five new lipopeptides, N-alpha-acyl-N-epsilon-acyl lysine
      analogues, were obtained. Minimum inhibitory concentration and minimum
      bactericidal (fungicidal) concentration were determined on reference strains of
      bacteria and fungi to evaluate the antimicrobial activity of the lipopeptides.
      Toxicity to eukaryotic cells was examined via determination of the haemolytic
      activities. The surface-active properties of these compounds were evaluated by
      measuring the surface tension and formation of micelles as a function of
      concentration in aqueous solution. The cationic surfactants demonstrated diverse
      antibacterial activities dependent on the length of the fatty acid chain. Gram
      negative bacteria and fungi showed a higher resistance than Gram-positive
      bacterial strains. It was found that the haemolytic activities were also chain
      length-dependent values. The surface-active properties showed a linear
      correlation between the alkyl chain length and the critical micelle
      concentration. 

PMID- 24748100
TI  - Abstracts from the American College of Pediatric Radiology Annual Meeting, May 14
      17, 2014, Washington DC.

PMID- 24748101
TI  - Histone acetylation and CREB binding protein are required for neuronal resistance
      against ischemic injury.
AB  - Epigenetic transcriptional regulation by histone acetylation depends on the
      balance between histone acetyltransferase (HAT) and deacetylase activities
      (HDAC). Inhibition of HDAC activity provides neuroprotection, indicating that the
      outcome of cerebral ischemia depends crucially on the acetylation status of
      histones. In the present study, we characterized the changes in histone
      acetylation levels in ischemia models of focal cerebral ischemia and identified
      cAMP-response element binding protein (CREB)-binding protein (CBP) as a crucial
      factor in the susceptibility of neurons to ischemic stress. Both neuron-specific
      RNA interference and neurons derived from CBP heterozygous knockout mice showed
      increased damage after oxygen-glucose deprivation (OGD) in vitro. Furthermore, we
      demonstrated that ischemic preconditioning by a short (5 min) subthreshold
      occlusion of the middle cerebral artery (MCA), followed 24 h afterwards by a 30
      min occlusion of the MCA, increased histone acetylation levels in vivo. Ischemic
      preconditioning enhanced CBP recruitment and histone acetylation at the promoter
      of the neuroprotective gene gelsolin leading to increased gelsolin expression in
      neurons. Inhibition of CBP's HAT activity attenuated neuronal ischemic
      preconditioning. Taken together, our findings suggest that the levels of CBP and
      histone acetylation determine stroke outcome and are crucially associated with
      the induction of an ischemia-resistant state in neurons. 

PMID- 24748102
TI  - Analysis of volatile compounds in exhaled breath condensate in patients with
      severe pulmonary arterial hypertension.
AB  - BACKGROUND: An important challenge to pulmonary arterial hypertension (PAH)
      diagnosis and treatment is early detection of occult pulmonary vascular
      pathology. Symptoms are frequently confused with other disease entities that lead
      to inappropriate interventions and allow for progression to advanced states of
      disease. There is a significant need to develop new markers for early disease
      detection and management of PAH. METHODOLGY AND FINDINGS: Exhaled breath
      condensate (EBC) samples were compared from 30 age-matched normal healthy
      individuals and 27 New York Heart Association functional class III and IV
      idiopathic pulmonary arterial hypertenion (IPAH) patients, a subgroup of PAH.
      Volatile organic compounds (VOC) in EBC samples were analyzed using gas
      chromatography/mass spectrometry (GC/MS). Individual peaks in GC profiles were
      identified in both groups and correlated with pulmonary hemodynamic and clinical
      endpoints in the IPAH group. Additionally, GC/MS data were analyzed using
      autoregression followed by partial least squares regression (AR/PLSR) analysis to
      discriminate between the IPAH and control groups. After correcting for
      medicaitons, there were 62 unique compounds in the control group, 32 unique
      compounds in the IPAH group, and 14 in-common compounds between groups. Peak-by
      peak analysis of GC profiles of IPAH group EBC samples identified 6 compounds
      significantly correlated with pulmonary hemodynamic variables important in IPAH
      diagnosis. AR/PLSR analysis of GC/MS data resulted in a distinct and identifiable
      metabolic signature for IPAH patients. CONCLUSIONS: These findings indicate the
      utility of EBC VOC analysis to discriminate between severe IPAH and a healthy
      population; additionally, we identified potential novel biomarkers that
      correlated with IPAH pulmonary hemodynamic variables that may be important in
      screening for less severe forms IPAH.

PMID- 24748103
TI  - Individuals with autism spectrum disorders do not use social stereotypes in irony
      comprehension.
AB  - Social and communication impairments are part of the essential diagnostic
      criteria used to define Autism Spectrum Disorders (ASDs). Difficulties in
      appreciating non-literal speech, such as irony in ASDs have been explained as due
      to impairments in social understanding and in recognizing the speaker's
      communicative intention. It has been shown that social-interactional factors,
      such as a listener's beliefs about the speaker's attitudinal propensities (e.g.,
      a tendency to use sarcasm, to be mocking, less sincere and more prone to
      criticism), as conveyed by an occupational stereotype, do influence a listener's
      interpretation of potentially ironic remarks. We investigate the effect of
      occupational stereotype on irony detection in adults with High Functioning Autism
      or Asperger Syndrome (HFA/AS) and a comparison group of typically developed
      adults. We used a series of verbally presented stories containing ironic or
      literal utterances produced by a speaker having either a "sarcastic" or a "non
      sarcastic" occupation. Although individuals with HFA/AS were able to recognize
      ironic intent and occupational stereotypes when the latter are made salient,
      stereotype information enhanced irony detection and modulated its social meaning
      (i.e., mockery and politeness) only in comparison participants. We concluded that
      when stereotype knowledge is not made salient, it does not automatically affect
      pragmatic communicative processes in individuals with HFA/AS. 

PMID- 24748104
TI  - Genome-wide analysis of loss of heterozygosity in breast infiltrating ductal
      carcinoma distant normal tissue highlights arm specific enrichment and expansion
      across tumor stages.
AB  - Studies have shown concurrent loss of heterozygosity (LOH) in breast infiltrating
      ductal carcinoma (IDC) and adjacent or distant normal tissue. However, the
      overall extent of LOH in normal tissue and their significance to tumorigenesis
      remain unknown, as existing studies are largely based on selected microsatellite
      markers. Here we present the first autosome-wide study of LOH in IDC and distant
      normal tissue using informative loci deduced from SNP array-based and sequencing
      based techniques. We show a consistently high LOH concurrence rate in IDC (mean =
      24%) and distant normal tissue (m = 54%), suggesting for most patients (31/33)
      histologically normal tissue contains genomic instability that can be a potential
      marker of increased IDC risk. Concurrent LOH is more frequent in fragile site
      related genes like WWOX (9/31), NTRK2 (10/31), and FHIT (7/31) than traditional
      genetic markers like BRCA1 (0/23), BRCA2 (2/29) and TP53 (1/13). Analysis at arm
      level shows distant normal tissue has low level but non-random enrichment of LOH
      (topped by 8p and 16q) significantly correlated with matched IDC (Pearson r =
      0.66, p = 3.5E-6) (topped by 8p, 11q, 13q, 16q, 17p, and 17q). The arm-specific
      LOH enrichment was independently observed in tumor samples from 548 IDC patients
      when stratified by tumor size based T stages. Fine LOH structure from sequencing
      data indicates LOH in low order tissues non-randomly overlap (~67%) with LOH that
      usually has longer tract length (the length of genomic region affected by LOH) in
      high order tissues. The consistent observations from multiple datasets suggest
      progressive LOH in the development of IDC potentially through arm-specific pile
      up effect with discernible signature in normal tissue. Our finding also suggests
      that LOH detected in IDC by comparing to paired adjacent or distant normal tissue
      are more likely underestimated. 

PMID- 24748107
TI  - DALY calculation in practice: a stepwise approach.

PMID- 24748105
TI  - Mutations in CENPE define a novel kinetochore-centromeric mechanism for
      microcephalic primordial dwarfism.
AB  - Defects in centrosome, centrosomal-associated and spindle-associated proteins are
      the most frequent cause of primary microcephaly (PM) and microcephalic primordial
      dwarfism (MPD) syndromes in humans. Mitotic progression and segregation defects,
      microtubule spindle abnormalities and impaired DNA damage-induced G2-M cell cycle
      checkpoint proficiency have been documented in cell lines from these patients.
      This suggests that impaired mitotic entry, progression and exit strongly
      contribute to PM and MPD. Considering the vast protein networks involved in
      coordinating this cell cycle stage, the list of potential target genes that could
      underlie novel developmental disorders is large. One such complex network, with a
      direct microtubule-mediated physical connection to the centrosome, is the
      kinetochore. This centromeric-associated structure nucleates microtubule
      attachments onto mitotic chromosomes. Here, we described novel compound
      heterozygous variants in CENPE in two siblings who exhibit a profound MPD
      associated with developmental delay, simplified gyri and other isolated
      abnormalities. CENPE encodes centromere-associated protein E (CENP-E), a core
      kinetochore component functioning to mediate chromosome congression initially of
      misaligned chromosomes and in subsequent spindle microtubule capture during
      mitosis. Firstly, we present a comprehensive clinical description of these
      patients. Then, using patient cells we document abnormalities in spindle
      microtubule organization, mitotic progression and segregation, before modeling
      the cellular pathogenicity of these variants in an independent cell system. Our
      cellular analysis shows that a pathogenic defect in CENP-E, a kinetochore-core
      protein, largely phenocopies PCNT-mutated microcephalic osteodysplastic
      primordial dwarfism-type II patient cells. PCNT encodes a centrosome-associated
      protein. These results highlight a common underlying pathomechanism. Our findings
      provide the first evidence for a kinetochore-based route to MPD in humans. 

PMID- 24748108
TI  - Technical tips and advancements in pediatric minimally invasive surgical training
      on porcine based simulations.
AB  - BACKGROUND: Minimal access techniques have transformed the way pediatric surgery
      is practiced. Due to various constraints, surgical residency programs have not
      been able to tutor adequate training skills in the routine setting. The advent of
      new technology and methods in minimally invasive surgery (MIS), has similarly
      contributed to the need for systematic skills' training in a safe, simulated
      environment. To enable the training of the proper technique among pediatric
      surgery trainees, we have advanced a porcine non-survival model for endoscopic
      surgery. MATERIALS AND METHODS: The technical advancements over the past 3 years
      and a subjective validation of the porcine model from 114 participating trainees
      using a standard questionnaire and a 5-point Likert scale have been described
      here. Mean attitude scores and analysis of variance (ANOVA) were used for
      statistical analysis of the data. RESULTS: Almost all trainees agreed or strongly
      agreed that the animal-based model was appropriate (98.35%) and also acknowledged
      that such workshops provided adequate practical experience before attempting on
      human subjects (96.6%). Mean attitude score for respondents was 19.08 (SD 3.4,
      range 4-20). Attitude scores showed no statistical association with years of
      experience or the level of seniority, indicating a positive attitude among all
      groups of respondents. CONCLUSIONS: Structured porcine-based MIS training should
      be an integral part of skill acquisition for pediatric surgery trainees and the
      experience gained can be transferred into clinical practice. We advocate that
      laparoscopic training should begin in a controlled workshop setting before
      procedures are attempted on human patients.

PMID- 24748106
TI  - Molecular characterization and phylogenetic analysis of H3 subtype avian
      influenza viruses isolated from domestic ducks in Zhejiang Province in China.
AB  - In 2013, 15 avian influenza viruses (AIVs), H3N2 (n = 7), H3N3 (n = 3), H3N6 (n =
      3), and H3N8 (n = 2), were isolated from domestic ducks in Zhejiang Province in
      China. These strains were characterized by whole genome sequencing with
      subsequent phylogenetic analysis and genetic comparison. Phylogenetic analysis of
      all eight viral genes showed that these strains clustered in the AIV Eurasian
      lineage. Analysis of the neuraminidase (NA) gene indicates that a re-assortment
      event between H3 and H9N2 AIV occurred in these ducks. The molecular markers
      analyzed over the genome of all viruses indicated that these strains were low
      pathogenic AIVs. Although there was no evidence of re-assortment in subtype H3
      AIVs among the avian species' and mammalian hosts in this study, continued
      surveillance is needed considering the important role of domestic ducks in AIV re
      assortment.

PMID- 24748109
TI  - Afterword: elaborating health and medicine's publics.
AB  - This essay argues that medical and health humanists interested in the rhetorical
      work of publics can extend their research by attending to embodiment and
      infrastructure. In addition to discussing how such strategies are illustrated in
      the essays appearing in this special issue, I relate them to the rhetorical study
      of personal health records (PHRs) as described in consumer-directed arguments. I
      conclude by posing two questions to health and medical humanists: "How do
      discursive constructions of publics and more specific instantiations of embodied
      experiences mutually shape each other?" and "What do the infrastructures of
      health and medical users look like and involve in their enactment?" 

PMID- 24748110
TI  - Stoichiometry and specific assembly of Best ion channels.
AB  - Human Bestrophin 1 (hBest1) is a calcium-activated chloride channel that
      regulates neuronal excitability, synaptic activity, and retinal homeostasis.
      Mutations in hBest1 cause the autosomal-dominant Best macular dystrophy (BMD).
      Because hBest1 mutations cause BMD, but a knockout does not, we wondered if
      hBest1 mutants exert a dominant negative effect through interaction with other
      calcium-activated chloride channels, such as hBest2, 3, or 4, or transmembrane
      member 16A (TMEM16A), a member of another channel family. The subunit
      architecture of Best channels is debated, and their ability to form heteromeric
      channel assemblies is unclear. Using single-molecule subunit analysis, we find
      that each of hBest1, 2, 3, and 4 forms a homotetrameric channel. Despite
      considerable conservation among hBests, hBest1 has little or no interaction with
      other hBests or mTMEM16A. We identify the domain responsible for assembly
      specificity. This domain also plays a role in channel function. Our results
      indicate that Best channels preferentially self-assemble into homotetramers. 

PMID- 24748111
TI  - CasA mediates Cas3-catalyzed target degradation during CRISPR RNA-guided
      interference.
AB  - In bacteria, the clustered regularly interspaced short palindromic repeats
      (CRISPR)-associated (Cas) DNA-targeting complex Cascade (CRISPR-associated
      complex for antiviral defense) uses CRISPR RNA (crRNA) guides to bind
      complementary DNA targets at sites adjacent to a trinucleotide signature sequence
      called the protospacer adjacent motif (PAM). The Cascade complex then recruits
      Cas3, a nuclease-helicase that catalyzes unwinding and cleavage of foreign double
      stranded DNA (dsDNA) bearing a sequence matching that of the crRNA. Cascade
      comprises the CasA-E proteins and one crRNA, forming a structure that binds and
      unwinds dsDNA to form an R loop in which the target strand of the DNA base pairs
      with the 32-nt RNA guide sequence. Single-particle electron microscopy
      reconstructions of dsDNA-bound Cascade with and without Cas3 reveal that Cascade
      positions the PAM-proximal end of the DNA duplex at the CasA subunit and near the
      site of Cas3 association. The finding that the DNA target and Cas3 colocalize
      with CasA implicates this subunit in a key target-validation step during DNA
      interference. We show biochemically that base pairing of the PAM region is
      unnecessary for target binding but critical for Cas3-mediated degradation. In
      addition, the L1 loop of CasA, previously implicated in PAM recognition, is
      essential for Cas3 activation following target binding by Cascade. Together,
      these data show that the CasA subunit of Cascade functions as an essential
      partner of Cas3 by recognizing DNA target sites and positioning Cas3 adjacent to
      the PAM to ensure cleavage. 

PMID- 24748112
TI  - Cortical control of adaptation and sensory relay mode in the thalamus.
AB  - A major synaptic input to the thalamus originates from neurons in cortical layer
      6 (L6); however, the function of this cortico-thalamic pathway during sensory
      processing is not well understood. In the mouse whisker system, we found that
      optogenetic stimulation of L6 in vivo results in a mixture of hyperpolarization
      and depolarization in the thalamic target neurons. The hyperpolarization was
      transient, and for longer L6 activation (>200 ms), thalamic neurons reached a
      depolarized resting membrane potential which affected key features of thalamic
      sensory processing. Most importantly, L6 stimulation reduced the adaptation of
      thalamic responses to repetitive whisker stimulation, thereby allowing thalamic
      neurons to relay higher frequencies of sensory input. Furthermore, L6 controlled
      the thalamic response mode by shifting thalamo-cortical transmission from
      bursting to single spiking. Analysis of intracellular sensory responses suggests
      that L6 impacts these thalamic properties by controlling the resting membrane
      potential and the availability of the transient calcium current IT, a hallmark of
      thalamic excitability. In summary, L6 input to the thalamus can shape both the
      overall gain and the temporal dynamics of sensory responses that reach the
      cortex. 

PMID- 24748113
TI  - Long-range repulsion of colloids driven by ion exchange and diffusiophoresis.
AB  - Interactions between surfaces and particles in aqueous suspension are usually
      limited to distances smaller than 1 MUm. However, in a range of studies from
      different disciplines, repulsion of particles has been observed over distances of
      up to hundreds of micrometers, in the absence of any additional external fields.
      Although a range of hypotheses have been suggested to account for such behavior,
      the physical mechanisms responsible for the phenomenon still remain unclear. To
      identify and isolate these mechanisms, we perform detailed experiments on a well
      defined experimental system, using a setup that minimizes the effects of gravity
      and convection. Our experiments clearly indicate that the observed long-range
      repulsion is driven by a combination of ion exchange, ion diffusion, and
      diffusiophoresis. We develop a simple model that accounts for our data; this
      description is expected to be directly applicable to a wide range of systems
      exhibiting similar long-range forces. 

PMID- 24748114
TI  - Iron oxide nanoparticles induce oxidative stress, DNA damage, and caspase
      activation in the human breast cancer cell line.
AB  - Broad applications of iron oxide nanoparticles require an improved understanding
      of their potential effects on human health. In the present study, we explored the
      underlying mechanism through which iron oxide nanoparticles induce toxicity in
      human breast cancer cells (MCF-7). MTT (3-(4, 5-dimethylthiazol-2-yl)-2, 5
      diphenyltetrazolium bromide) and lactate dehydrogenase assays were used to
      examine mechanisms of cytotoxicity. Concentration- and time-dependent
      cytotoxicity was observed in MCF-7 cells. Iron oxide nanoparticles were found to
      induce oxidative stress evidenced by the elevation of reactive oxygen species
      generation, lipid peroxidation, and depletion of superoxide dismutase,
      glutathione, and catalase activities in MCF-7 cells. Nuclear staining was
      performed using 4', 6-diamidino-2-phenylindole (DAPI), and cells were analyzed
      with a fluorescence microscope. Iron oxide nanoparticles (60 MUg/ml) induced
      substantial apoptosis that was identified by morphology, condensation, and
      fragmentation of the nuclei of the MCF-7 cells. It was also observed that the
      iron oxide NPs induced caspase-3 activity. DNA strand breakage was detected by
      comet assay, and it occurred in a concentration- and time-dependent manner. Thus,
      the data indicate that iron oxide nanoparticles induced cytotoxicity and
      genotoxicity in MCF-7 cells via oxidative stress. This study warrants more
      careful assessment of iron oxide nanoparticles before their industrial
      applications. 

PMID- 24748115
TI  - Pharmacological characterization of cultivated neuronal networks: relevance to
      synaptogenesis and synaptic connectivity.
AB  - Mental disorders, such as schizophrenia or Alzheimer's disease, are associated
      with impaired synaptogenesis and/or synaptic communication. During development,
      neurons assemble into neuronal networks, the primary supracellular mediators of
      information processing. In addition to the orchestrated activation of genetic
      programs, spontaneous electrical activity and associated calcium signaling have
      been shown to be critically involved in the maturation of such neuronal networks.
      We established an in vitro model that recapitulates the maturation of neuronal
      networks, including spontaneous electrical activity. Upon plating, mouse primary
      hippocampal neurons grow neurites and interconnect via synapses to form a dish
      wide neuronal network. Via live cell calcium imaging, we identified a limited
      period of time in which the spontaneous activity synchronizes across neurons,
      indicative of the formation of a functional network. After establishment of
      network activity, the neurons grow dendritic spines, the density of which was
      used as a morphological readout for neuronal maturity and connectivity. Hence,
      quantification of neurite outgrowth, synapse density, spontaneous neuronal
      activity, and dendritic spine density allowed to study neuronal network
      maturation from the day of plating until the presence of mature neuronal
      networks. Via acute pharmacological intervention, we show that synchronized
      network activity is mediated by the NMDA-R. The balance between kynurenic and
      quinolinic acid, both neuro-active intermediates in the tryptophan/kynurenine
      pathway, was shown to be decisive for the maintenance of network activity.
      Chronic modulation of the neurotrophic support influenced the network formation
      and revealed the extreme sensitivity of calcium imaging to detect subtle
      alterations in neuronal physiology. Given the reproducible cultivation in a 96
      well setup in combination with fully automated analysis of the calcium
      recordings, this approach can be used to build a high-content screening assay
      usable for neurotoxicity screening, target identification/validation, or
      phenotypic drug screening.

PMID- 24748117
TI  - Is memantine + acetylcholinesterase inhibitor treatment superior to either
      therapy alone in Alzheimer's disease?
AB  - Alzheimer's disease is the most common form of dementia in the elderly.
      Currently, there is no established standard treatment for this disease;
      therefore, the treatment of Alzheimer's disease will be a major challenge for
      physicians in the next decade in order to ameliorate quality of life of patients
      and reduce the costs for the communities. 

PMID- 24748116
TI  - End-binding protein 1 stimulates paclitaxel sensitivity in breast cancer by
      promoting its actions toward microtubule assembly and stability.
AB  - Paclitaxel is a microtubule-targeting agent widely used for the treatment of many
      solid tumors. However, patients show variable sensitivity to this drug, and
      effective diagnostic tests predicting drug sensitivity remain to be investigated.
      Herein, we show that the expression of end-binding protein 1 (EB1), a regulator
      of microtubule dynamics involved in multiple cellular activities, in breast tumor
      tissues correlates with the pathological response of tumors to paclitaxel-based
      chemotherapy. In vitro cell proliferation assays reveal that EB1 stimulates
      paclitaxel sensitivity in breast cancer cell lines. Our data further demonstrate
      that EB1 increases the activity of paclitaxel to cause mitotic arrest and
      apoptosis in cancer cells. In addition, microtubule binding affinity analysis and
      polymerization/depolymerization assays show that EB1 enhances paclitaxel binding
      to microtubules and stimulates the ability of paclitaxel to promote microtubule
      assembly and stabilization. These findings thus reveal EB1 as a critical
      regulator of paclitaxel sensitivity and have important implications in breast
      cancer chemotherapy. 

PMID- 24748118
TI  - Ventricular and lumbar cerebrospinal fluid concentrations of Alzheimer's disease
      biomarkers in patients with normal pressure hydrocephalus and posttraumatic
      hydrocephalus.
AB  - BACKGROUND: Little information is available on the rostro-caudal concentration
      gradient of Alzheimer's disease (AD) biomarkers. OBJECTIVE: We studied the
      concentrations of amyloid-beta (Abeta) peptides 1-42 and 1-40 as well as the Tau
      and pTau proteins in simultaneously collected ventricular and lumbar
      cerebrospinal fluid (CSF) samples. METHODS: The samples were simultaneously
      collected from the ventricle and the lumbar spinal canal in two groups of
      patients: 10 subjects being treated for normal pressure hydrocephalus (NPH) by
      the placement of a ventriculo-peritoneal shunt and 5 patients treated
      simultaneously with an external ventricular drain and a lumbar CSF drain due to
      posttraumatic hydrocephalus (PTH). RESULTS: The ventricular-lumbar (V/L)
      concentration ratio for Abeta1-40 was 0.81 in NPH patients and 0.71 in PTH
      patients. The V/L-ratio for Abeta1-42 was 0.84 in NPH, reflecting significantly
      higher concentrations in lumbar CSF than in ventricular CSF, and 1.02 in PTH
      patients. The V/L-ratios for Tau and pTau differed significantly depending on the
      diagnostic group: the median V/L-ratio for Tau was 6.83 in NPH patients but only
      0.97 in PTH patients. The median V/L-ratio for pTau was 2.36 in NPH patients and
      0.91 in PTH patients. CONCLUSIONS: We conclude that the rostro-caudal
      concentration gradient for brain-derived proteins (Tau and pTau in this study)
      depends on the diagnosis and clinical status of the patient, which were largely
      neglected in the previously postulated models.

PMID- 24748119
TI  - Regulation of neuronal cytoskeletal protein phosphorylation in neurodegenerative
      diseases.
AB  - Neuronal cytoskeletal proteins such as neurofilaments (NFs) and tau are
      aberrantly and hyperphosphorylated in neurodegeneration. Under normal
      physiological conditions, NFs are synthesized in the cell bodies and
      phosphorylated and transported in the axonal compartment. However, under
      neurodegenerative disorders such as Alzheimer's disease (AD), spinal cord motor
      neuron inclusions of amyotrophic lateral sclerosis, Lewy bodies of Parkinson's
      disease, Pick's disease, Charcot-Marie-Tooth disease, and diabetic neuropathy,
      NFs are aberrantly and hyperphosphorylated in cell bodies. The proline directed
      protein kinases, such as cyclin-dependent protein kinase 5, mitogen activated
      protein kinase, and glycogen synthase kinase 3beta, and the non proline-directed
      kinases, such as casein kinase 1, are deregulated in AD. Moreover, the reversible
      phosphorylation by protein phosphatase, PP2A, which mainly carries out the
      dephosphorylation of tau and NFs, is down regulated in AD brain. The aberrant
      phosphorylation of cytoskeletal proteins such as tau and NFs results in the
      axonal transport defects in neurodegeneration. The peptidyl-prolyl isomerase Pin1
      plays a regulatory role in the post-phosphorylation mechanism of neuronal
      cytoskeletal proteins in AD brain. Possible therapeutic interventions for
      neurodegenerative disorders are (1) inhibition of proline-directed kinases, (2)
      activation of protein phosphatases such as PP2A, and (3) modulation of peptidyl
      prolyl isomerases such as Pin1. Here, I discuss the regulation of neuronal
      cytoskeletal proteins under physiology and pathology.

PMID- 24748120
TI  - Lipidated peptides via post-synthetic thioalkylation promoted by molecular
      sieves.
AB  - A thioalkylation procedure, which uses molecular sieves to promote the reaction,
      was exploited to provide peptides with useful functional groups (lipidic
      moieties), naturally occurring on proteins as post-translational modifications.
      The procedure was further implemented to synthesize tailor-made lipidated
      peptides, interesting tools to investigate biological processes involving their
      Ras parent proteins. Moreover, the one-pot preparation of multi-alkylated
      peptides confirms the versatility and flexibility of the employed methodology. 

PMID- 24748121
TI  - A new lncRNA, APTR, associates with and represses the CDKN1A/p21 promoter by
      recruiting polycomb proteins.
AB  - Long noncoding RNAs (lncRNAs) have emerged as a major regulator of cell
      physiology, but many of which have no known function. CDKN1A/p21 is an important
      inhibitor of the cell-cycle, regulator of the DNA damage response and effector of
      the tumor suppressor p53, playing a crucial role in tumor development and
      prevention. In order to identify a regulator for tumor progression, we performed
      an siRNA screen of human lncRNAs required for cell proliferation, and identified
      a novel lncRNA, APTR, that acts in trans to repress the CDKN1A/p21 promoter
      independent of p53 to promote cell proliferation. APTR associates with the
      promoter of CDKN1A/p21 and this association requires a complementary-Alu sequence
      encoded in APTR. A different module of APTR associates with and recruits the
      Polycomb repressive complex 2 (PRC2) to epigenetically repress the p21 promoter.
      A decrease in APTR is necessary for the induction of p21 after heat stress and
      DNA damage by doxorubicin, and the levels of APTR and p21 are anti-correlated in
      human glioblastomas. Our data identify a new regulator of the cell-cycle
      inhibitor CDKN1A/p21 that acts as a proliferative factor in cancer cell lines and
      in glioblastomas and demonstrate that Alu elements present in lncRNAs can
      contribute to targeting regulatory lncRNAs to promoters. 

PMID- 24748122
TI  - Interceptor effect of C60 fullerene on the in vitro action of aromatic drug
      molecules.
AB  - C60 fullerenes are spherical molecules composed purely of carbon atoms. They
      inspire a particularly strong scientific interest because of their specific
      physico-chemical properties and potential medical and nanotechnological
      applications. In this work we are focusing on studying the influence of the
      pristine C60 fullerene on biological activity of some aromatic drug molecules in
      human buccal epithelial cells. Assessment of the heterochromatin structure in the
      cell nucleus as well as the barrier function of the cell membrane was performed.
      The methods of cell microelectrophoresis and atomic force microscopy were also
      applied. A concentration-dependent restoration of the functional activity of the
      cellular nucleus after exposure to DNA-binding drugs (doxorubicin, proflavine and
      ethidium bromide) has been observed in human buccal epithelial cells upon
      addition of C60 fullerene at a concentration of ~10(-5 )M. The results were shown
      to follow the framework of interceptor/protector action theory, assuming that non
      covalent complexation between C60 fullerene and the drugs (i.e., hetero
      association) is the major process responsible for the observed biological
      effects. An independent confirmation of this hypothesis was obtained via
      investigation of the cellular response of buccal epithelium to the
      coadministration of the aromatic drugs and caffeine, and it is based on the well
      established role of hetero-association in drug-caffeine systems. The results
      indicate that C60 fullerene may reverse the effects caused by the aromatic drugs,
      thereby pointing out the potential possibility of the use of aromatic drugs in
      combination with C60 fullerene for regulation of their medico-biological action.

PMID- 24748123
TI  - Wild-type measles viruses with non-standard genome lengths.
AB  - The length of the single stranded, negative sense RNA genome of measles virus
      (MeV) is highly conserved at 15,894 nucleotides (nt). MeVs can be grouped into 24
      genotypes based on the highly variable 450 nucleotides coding for the carboxyl
      terminus of the nucleocapsid protein (N-450). Here, we report the genomic
      sequences of 2 wild-type viral isolates of genotype D4 with genome lengths of
      15,900 nt. Both genomes had a 7 nt insertion in the 3' untranslated region (UTR)
      of the matrix (M) gene and a 1 nt deletion in the 5' UTR of the fusion (F) gene.
      The net gain of 6 nt complies with the rule-of-six required for replication
      competency of the genomes of morbilliviruses. The insertions and deletion
      (indels) were confirmed in a patient sample that was the source of one of the
      viral isolates. The positions of the indels were identical in both viral
      isolates, even though epidemiological data and the 3 nt differences in N-450
      between the two genomes suggested that the viruses represented separate chains of
      transmission. Identical indels were found in the M-F intergenic regions of 14
      additional genotype D4 viral isolates that were imported into the US during 2007
      2010. Viral isolates with and without indels produced plaques of similar size and
      replicated efficiently in A549/hSLAM and Vero/hSLAM cells. This is the first
      report of wild-type MeVs with genome lengths other than 15,894 nt and
      demonstrates that the length of the M-F UTR of wild-type MeVs is flexible. 

PMID- 24748124
TI  - Acylated phenylethanoid glycosides, echinacoside and acteoside from Cistanche
      tubulosa, improve glucose tolerance in mice.
AB  - Acylated phenylethanoid glycosides, echinacoside (1) and acteoside (2), principal
      constituents in stems of Cistanche tubulosa (Orobanchaceae), inhibited the
      increase in postprandial blood glucose levels in starch-loaded mice at doses of
      250-500 mg/kg p.o. These compounds (1 and 2) also significantly improved glucose
      tolerance in starch-loaded mice after 2 weeks of continuous administration at
      doses of 125 and/or 250 mg/kg/day p.o. without producing significant changes in
      body weight or food intake. In addition, several constituents from C. tubulosa,
      including 1 (IC50 = 3.1 MUM), 2 (1.2 MUM), isoacteoside (3, 4.6 MUM), 2'
      acetylacteoside (4, 0.071 MUM), tubulosides A (5, 8.8 MUM) and B (9, 4.0 MUM),
      syringalide A 3-O-alpha-L-rhamnopyranoside (10, 1.1 MUM), campneoside I (13, 0.53
      MUM), and kankanoside J1 (14, 9.3 MUM), demonstrated potent rat lens aldose
      reductase inhibitory activity. In particular, the potency of compound 4 was
      similar to that of epalrestat (0.072 MUM), a clinical aldose reductase inhibitor.

PMID- 24748125
TI  - Comparative QTL analysis of root lesion nematode resistance in barley.
AB  - KEY MESSAGE: This study demonstrates for the first time that resistance to
      different root lesion nematodes ( P. neglectus and P. penetrans ) is controlled
      by a common QTL. A major resistance QTL ( Rlnnp6H ) has been mapped to chromosome
      6H using two independent barley populations. Root lesion nematodes (Pratylenchus
      spp.) are important pests in cereal production worldwide. We selected two doubled
      haploid populations of barley (Igri * Franka and Uschi * HHOR 3073) and infected
      them with Pratylenchus penetrans and Pratylenchus neglectus. Nematode
      multiplication rates were measured 7 or 10 weeks after infection. In both
      populations, continuous phenotypic variations for nematode multiplication rates
      were detected indicating a quantitative inheritance of resistance. In the Igri *
      Franka population, four P. penetrans resistance QTLs were mapped with 857
      molecular markers on four linkage groups (2H, 5H, 6H and 7H). In the Uschi * HHOR
      3073 population, eleven resistance QTLs (P. penetrans and P. neglectus) were
      mapped with 646 molecular markers on linkage groups 1H, 3H, 4H, 5H, 6H and 7H. A
      major resistance QTL named Rlnnp6H (LOD score 6.42-11.19) with a large phenotypic
      effect (27.5-36.6 %) for both pests was mapped in both populations to chromosome
      6H. Another resistance QTL for both pests was mapped on linkage group 5H (Igri *
      Franka population). These data provide first evidence for common resistance
      mechanisms against different root lesion nematode species. The molecular markers
      are a powerful tool for the selection of resistant barley lines among segregating
      populations because resistance tests are time consuming and laborious.

PMID- 24748126
TI  - QTL for resistance to root lesion nematode (Pratylenchus thornei) from a
      synthetic hexaploid wheat source.
AB  - KEY MESSAGE: A whole genome average interval mapping approach identified eight
      QTL associated with P. thornei resistance in a DH population from a cross between
      the synthetic-derived wheat Sokoll and cultivar Krichauff. Pratylenchus thornei
      are migratory nematodes that feed and reproduce within the wheat root cortex,
      causing cell death (lesions) resulting in severe yield reductions globally.
      Genotypic selection using molecular markers closely linked to Pratylenchus
      resistance genes will accelerate the development of new resistant cultivars by
      reducing the need for laborious and expensive resistance phenotyping. A doubled
      haploid wheat population (150 lines) from a cross between the synthetic-derived
      cultivar Sokoll (P. thornei resistant) and cultivar Krichauff (P. thornei
      moderately susceptible) was used to identify quantitative trait loci (QTL)
      associated with P. thornei resistance. The resistance identified in the
      glasshouse was validated in a field trial. A genetic map was constructed using
      Diversity Array Technology and the QTL regions identified were further targeted
      with simple sequence repeat (SSR) and single-nucleotide polymorphism (SNP)
      markers. Six significant and two suggestive P. thornei resistance QTL were
      detected using a whole genome average interval mapping approach. Three QTL were
      identified on chromosome 2B, two on chromosome 6D, and a single QTL on each of
      chromosomes 2A, 2D and 5D. The QTL on chromosomes 2BS and 6DS mapped to locations
      previously identified to be associated with Pratylenchus resistance. Together,
      the QTL on 2B (QRlnt.sk-2B.1-2B.3) and 6D (QRlnt.sk-6D.1 and 6D.2) explained 30
      and 48 % of the genotypic variation, respectively. Flanking PCR-based markers
      based on SSRs and SNPs were developed for the major QTL on 2B and 6D and provide
      a cost-effective high-throughput tool for marker-assisted breeding of wheat with
      improved P. thornei resistance.

PMID- 24748127
TI  - Micro RNA-373 is down-regulated in pancreatic cancer and inhibits cancer cell
      invasion.
AB  - BACKGROUND: Micro RNAs (miRNAs) are small noncoding RNAs that have gained
      attention as key molecules in the malignant characteristics of cancers, and
      several recent investigations also have identified some miRNAs as potential key
      regulators to inhibit the malignant characteristics of tumors. MiRNA-373 (miR
      373) has recently been reported to induce E-cadherin, which is a key regulator of
      epithelial-mesenchymal transition (EMT). However, the role of miR-373 in the
      characteristics of cancer cells is not still well known. METHODS: We investigated
      the expression levels of miR-373 in pancreatic cancer cell lines and its effect
      on the invasiveness of pancreatic cancer by using in vitro and in vivo models. We
      also analyzed the expression of miR-373 using formalin-fixed paraffin-embedded (n
      = 152) and microdissected frozen (n = 57) samples from pancreatic tissues.
      RESULTS: The levels of miR-373 expression were low in pancreatic cancer cell
      lines. In formalin-fixed paraffin-embedded and microdissected frozen samples, miR
      373 expression was significantly down-regulated in pancreatic cancer compared
      with that in healthy pancreas (P < 0.001 and P = 0.005, respectively). We also
      found that reexpression of miR-373 repressed transforming growth factor-beta
      induced EMT, leading to inhibition of invasiveness of cancer cells. Furthermore,
      reexpression of miR-373 significantly inhibited peritoneal dissemination in vivo
      (P < 0.001). CONCLUSIONS: MiR-373 is down-regulated in pancreatic cancer, and its
      reexpression represses the invasiveness of pancreatic cancer cells.

PMID- 24748128
TI  - Pathology review significantly affects diagnosis and treatment of melanoma
      patients: an analysis of 5011 patients treated at a melanoma treatment center.
AB  - BACKGROUND: Pathologists sometimes disagree on the diagnosis of melanoma or its
      histopathologic staging, which may have implications for treatment and follow-up.
      For this reason, melanoma patients referred to Melanoma Institute Australia (MIA)
      for further treatment routinely have their pathology slides reviewed by MIA
      pathologists. This study sought to determine whether diagnosis, staging, and
      treatment of melanoma patients changed significantly after central pathology
      review. METHODS: A total of 5,011 pairs of non-MIA and MIA pathology reports on
      the same primary melanoma specimen were reviewed. Differences in diagnosis,
      American Joint Committee on Cancer (AJCC) T classification, and treatment
      recommendations based on the non-MIA and MIA pathology reports were determined.
      RESULTS: A melanoma diagnosis changed in 5.1 % of cases after review. Where both
      pathologists agreed on a diagnosis of melanoma, AJCC T classification changed in
      22.1 % after review. After MIA review, planned surgical excision margins changed
      in 11.2 % of cases, and a recommendation for sentinel lymph node biopsy (SLNB)
      changed in 8.6 %. Non-MIA reports less frequently contained criteria to define
      AJCC T classification (86.6 vs. 97.6 %), select appropriate surgical excision
      margins (95.2 vs. 99.6 %) and make a recommendation for SLNB (94.5 vs. 99.4 %),
      (each p < 0.001). On multivariate analysis, partial biopsies were independently
      associated with more frequent changes in AJCC T classification (p < 0.001),
      planned surgical excision margins (p < 0.001), and SLNB recommendations (p <
      0.001) on the basis of MIA pathology review. CONCLUSIONS: Diagnosis, AJCC T
      classification, and treatment recommendations often change after pathology review
      by specialist melanoma pathologists. We recommend pathology review be considered
      for all patients attending specialist melanoma treatment centers.

PMID- 24748129
TI  - Significance of allelic percentage of BRAF c.1799T > A (V600E) mutation in
      papillary thyroid carcinoma.
AB  - BACKGROUND: Somatic BRAF mutation is frequently observed in papillary thyroid
      carcinoma (PTC). Recent evidence suggests that PTCs are heterogeneous tumors
      containing a subclonal or oligoclonal occurrence of BRAF mutation. Conflicting
      results have been reported concerning the prognostic significance of the mutant
      allele frequency. Our present aim was to investigate the association between the
      percentage of BRAF c.1799T > A (p.Val600Glu) alleles and clinicopathological
      parameters in PTC. METHODS: Genomic DNA was extracted from fresh-frozen specimens
      obtained from 50 PTC patients undergoing total thyroidectomy. The BRAF mutation
      status was determined by Sanger sequencing. The percentage of mutant BRAF alleles
      was quantified by mass spectrometric genotyping, pyrosequencing, and competitive
      allele-specific TaqMan PCR (castPCR). RESULTS: Positive rate of BRAF mutation was
      72 % by Sanger sequencing, 82 % by mass spectrometric genotying, and 84 % by
      pyrosequencing or castPCR. The average percentage of mutant BRAF alleles was
      22.5, 31, and 30.7 %, respectively. There was a good correlation among three
      quantification methods (Spearman's rho = 0.87-0.97; p < 0.0001). The mutant
      allele frequency was significantly correlated with tumor size (rho = 0.47-0.52; p
      < 0.01) and extrathyroidal invasion. The frequency showed no difference in
      pathological lymph node metastasis. CONCLUSIONS: The percentage of mutant BRAF
      alleles is positively associated with tumor burden and extrathyroidal invasion in
      PTC. Relatively good correlations exist among mass spectrometric genotyping,
      pyrosequencing, and castPCR in quantification of mutant BRAF allele frequency.

PMID- 24748130
TI  - How Spirituality Helps Cancer Patients with the Adjustment to their Disease.
AB  - It has been suggested that spirituality is associated with higher well-being,
      because it offers social support, improves the relationship with the partner,
      provides meaning, and reduces self-focus and worry. We performed a qualitative
      study among ten people with cancer, using the Consensual Qualitative Research
      method for the analysis of semi-structured interviews. Support was found for the
      mechanisms of meaning provision and of reduction of self-focus and worries.
      Participants also mentioned emotion-focused roles of spirituality: Feeling
      supported by a transcendental confidant, the expression of negative emotions (in
      prayer), acceptance, allowing feelings of misery, and viewing problems from a
      distance. There was no mention of a contribution of spirituality to adjustment
      through improved social support per se or a higher quality of the relationship
      with the partner. The results of the present study indicate that the role of
      spirituality in emotion regulation deserves attention in understanding how
      spirituality helps cancer patients to adjust to their disease. 

PMID- 24748131
TI  - Feasibility of sheathless transfemoral aortic valve implantation in patients with
      small access vessel diameters.
AB  - OBJECTIVES: We intended to show feasibility of sheathless transfemoral aortic
      valve implantation in patients with small access vessel diameters. BACKGROUND:
      Transcatheter aortic valve implantation (TAVI) has emerged as a valid treatment
      option in patients with aortic valve stenosis who are poor candidates for
      surgical aortic valve replacement. Few patients, who cannot undergo transfemoral
      or transsubclavian aortic valve implantation due to small access vessel
      diameters, are not suitable for transapical or direct aortic valve implantation,
      either. METHODS: In more than 700 transcatheter aortic valve implantations since
      2008 we identified 17 patients who had to be excluded from transfemoral valve
      implantation due to vessel diameters <6 mm and who were no candidates for
      transapical or direct aortic implantation. We performed CoreValveTM implantations
      in these patients without the required 18F sheath to cross the vessels despite
      their small size (4.6-5.9 mm). RESULTS: Sixteen sheathless implantations were
      successful. In all 17 patients, bleeding during the procedure due to the smaller
      delivery catheter was minimal. Sixteen patients had a successful access site
      closure at the end of the procedure. CONCLUSIONS: Sheathless implantation of a
      self-expanding aortic valve can be safely considered in selected patients with
      access vessel diameters below 6 mm, if transapical or direct aortic implantation
      is not suitable.

PMID- 24748132
TI  - The updated phylogenies of the phasianidae based on combined data of nuclear and
      mitochondrial DNA.
AB  - The phylogenetic relationships of species in the Phasianidae, Order Galliformes,
      are the object of intensive study. However, convergent morphological evolution
      and rapid species radiation result in much ambiguity in the group. Further,
      matrilineal (mtDNA) genealogies conflict with trees based on nuclear DNA
      retrotransposable elements. Herein, we analyze 39 nearly complete mitochondrial
      genomes (three new) and up to seven nuclear DNA segments. We combine these
      multiple unlinked, more informative genetic markers to infer historical
      relationships of the major groups of phasianids. The nuclear DNA tree is largely
      congruent with the tree derived from mt genomes. However, branching orders of
      mt/nuclear trees largely conflict with those based on retrotransposons. For
      example, Gallus/Bambusicola/Francolinus forms the sister-group of
      Coturnix/Alectoris in the nuclear/mtDNA trees, yet the tree based on
      retrotransposable elements roots the former at the base of the tree and not with
      the latter. Further, while peafowls cluster with Gallus/Coturnix in the mt tree,
      they root at the base of the phasianids following Gallus in the tree based on
      retrotransposable elements. The conflicting branch orders in nuclear/mtDNA and
      retrotransposons-based trees in our study reveal the complex topology of the
      Phasianidae. 

PMID- 24748133
TI  - In vitro calcite crystal morphology is modulated by otoconial proteins otolin-1
      and otoconin-90.
AB  - Otoconia are formed embryonically and are instrumental in detecting linear
      acceleration and gravity. Degeneration and fragmentation of otoconia in elderly
      patients leads to imbalance resulting in higher frequency of falls that are
      positively correlated with the incidence of bone fractures and death. In this
      work we investigate the roles otoconial proteins Otolin-1 and Otoconin 90 (OC90)
      perform in the formation of otoconia. We demonstrate by rotary shadowing and
      atomic force microscopy (AFM) experiments that Otolin-1 forms homomeric protein
      complexes and self-assembled networks supporting the hypothesis that Otolin-1
      serves as a scaffold protein of otoconia. Our calcium carbonate crystal growth
      data demonstrate that Otolin-1 and OC90 modulate in vitro calcite crystal
      morphology but neither protein is sufficient to produce the shape of otoconia.
      Coadministration of these proteins produces synergistic effects on crystal
      morphology that contribute to morphology resembling otoconia. 

PMID- 24748134
TI  - Panax ginseng extract modulates oxidative stress, DNA fragmentation and up
      regulate gene expression in rats sub chronically treated with aflatoxin B1 and
      fumonisin B 1.
AB  - Aflatoxins and fumonisins are important food-borne mycotoxins implicated in human
      health and have cytotoxic effects. The aims of the current study were to evaluate
      the protective role of Panax ginseng extract (PGE) against the synergistic effect
      of subchronic administration of aflatoxin B1 (AFB1) and fumonisin B1 (FB1) on DNA
      and gene expression in rat. Female Sprague-Dawley rats were divided into eight
      groups (ten rats/group) and treated for 12 weeks including the control group, the
      group having received AFB1 (80 ug/kg bw), the group having received FB1 (100
      ug/kg bw), the group having received AFB1 plus FB1 and the groups having received
      PGE (20 mg/kg bw) alone or with AFB1 and/or FB1. At the end of experiment, liver
      and kidney were collected for the determination of DNA fragmentation, lipid
      peroxidation (LP), glutathione (GSH) contents and alterations in gene expression.
      The results indicated that these mycotoxins increased DNA fragmentation, LP and
      decreased GSH content in liver and kidney and down-regulated gene expression of
      antioxidants enzymes. The combined treatments with AFB1 and/or FB1 plus PGE
      suppressed DNA fragmentation only in the liver, normalized LP and increased GSH
      in the liver and kidney as well as up-regulated the expression of GPx, SOD1 and
      CAT mRNA. It could be concluded that AFB1 and FB1 have synergistic genotoxic
      effects. PGE induced protective effects against their oxidative stress and
      genotoxicity through its antioxidant properties. 

PMID- 24748135
TI  - Tenosynovitis of the peroneal tendons associated with a hypertrophic peroneal
      tubercle: radiography and MRI findings.
AB  - An enlarged peroneal tubercle can cause a peroneal tendon tear and/or
      tenosynovitis due to chronic friction. We present the case of a 45-year-old man
      with tenosynovitis in the peroneus longus and brevis tendons associated with a
      hypertrophic peroneal tubercle. On admission to our facility, the patient
      presented with pain while walking and had a fixed mass on the lateral aspect of
      his right foot. In addition, an osseous prominence corresponding to a
      hypertrophic peroneal tubercle was seen on the lateral side of the right
      calcaneus on radiography. MRI confirmed the hypertrophic peroneal tubercle and
      revealed high-signal intensity within the peroneus longus and brevis tendons
      along with fluid in their sheaths. 

PMID- 24748136
TI  - Scalp fibroma: a rare cutaneous manifestation of tuberous sclerosis.
AB  - We report a case of a 23-year-old woman with a history of generalised tonic
      clonic seizures, reddish brown maculopapular swelling over the face and an
      enlarging swelling over the scalp. Physical examinations revealed angiofibroma of
      the face and other typical cutaneous lesions of tuberous sclerosis, for example,
      shagreen patch and periungual fibroma. Scalp swelling was labelled as fibroma by
      dermatologists, which was further supported by the histopathological findings.
      Fibroma of the face is one of the commonest lesions, however, fibroma of the
      scalp is a rarely described entity. 

PMID- 24748138
TI  - An unusual presentation of miliary tuberculosis.
AB  - A young Bangladeshi woman presented to the emergency department with vaginal
      discharge on a history of fevers and rigours. Although initially treated for
      pelvic inflammatory disease, the patient rapidly developed respiratory failure
      with acute respiratory distress syndrome. An axillary biopsy and a high
      resolution CT of the chest confirmed miliary tuberculosis (TB). She was initiated
      on anti-TB medication and made a rapid recovery. 

PMID- 24748137
TI  - The great masquerader: Behcet's disease.
AB  - This report describes the case of a 44-year-old Caucasian woman of Northern
      European descent with a medical history of pyoderma gangrenosum, chronic
      abdominal pain and erythema nodosum which required intermittent use of high-dose
      steroids that failed to improve her symptoms. The patient was initially diagnosed
      with Crohn's disease and most recently with sclerosing mesenteritis. She
      presented to the hospital with worsening abdominal pain. She was found to have
      recurrent painful aphthous oral, genital and perianal ulcers and a clinical
      diagnosis of Behcet's disease was made. Her hospitalisation was complicated by
      haemoptysis, and bronchoscopy revealed alveolar haemorrhage. Treatment was
      initiated with three days of pulse intravenous solumedrol 1 g/day and
      cyclophosphamide at 700 mg/m(2). The case had a favourable outcome despite the
      initial diagnostic challenges. This report emphasises that systemic diseases,
      including Behcet's disease, can have variable presentations and can be frequently
      misdiagnosed. 

PMID- 24748139
TI  - A case of recurrent gallstone ileus: the fate of the residual gallstone remains
      unknown.
AB  - Gallstone ileus is a serious complication of cholelithiasis where mechanical
      small bowel obstruction occurs. The recurrence of gallstone ileus is rare. The 67
      year-old woman in this case report had three known gallstones transit her small
      bowel with two causing obstruction and the third causing a 'tumbling phenomenon'.
      As we have an ageing population, and gallstone ileus has a higher incidence in
      the over 65 age group, associated with increased comorbidities and hence greater
      mortality rates, it is imperative to establish the best surgical intervention for
      it. This case report highlights the difference CT of the abdomen has made to the
      diagnosis of gallstone ileus and the pros and cons of the surgical management
      options. 

PMID- 24748140
TI  - Severe depression masquerading as Creutzfeldt-Jakob disease.
AB  - We report a case of melancholic depression with catatonic features presenting as
      a rapidly progressive organic brain syndrome, initially thought to be probable
      Creutzfeldt-Jakob disease. The case highlights the fundamental importance of
      thorough exclusion of treatable pathology masquerading as an irreversible
      syndrome. 

PMID- 24748141
TI  - Rare presentation of intracranial vascular blowout after tumor resection and
      radiation therapy.
AB  - A middle-aged patient presented with a rapidly growing right dural-based extra
      axial posterior clinoid mass extending to the right cavernous sinus that was
      surgically resected. Histological examination showed solid growth of primitive
      neuroectodermal tumor arising from the third nerve. Following surgical resection,
      the patient was further managed by radiation and chemotherapy. Two years later
      the patient developed new intracranial hemorrhage in the area adjacent to the
      previous surgical cavity. A cerebral angiogram showed contrast extravasation at
      the junction of the posterior communicating artery (Pcom) and the right posterior
      cerebral artery (PCA), with an expanding pseudoaneurysm. This was managed with N
      butyl cyanoacrylate embolization. Autopsy showed microscopic recurrence of tumor
      into the PCA/PCom region with invasion of the wall of the Pcom. This case report
      illustrates the concept of vascular blowout in intracranial cerebral vasculature.
      It appears that, in the presence of risk factors that contribute to weakening of
      vessel walls (surgery, radiation, tumor recurrence), a blowout can occur
      intracranially. 

PMID- 24748142
TI  - Breast cancer, DPYD mutations and capecitabine-related ileitis: description of
      two cases and a review of the literature.
AB  - Despite many treatment advances, metastatic breast cancer remains an incurable
      disease and is the third leading cause of cancer-related deaths in Europe.
      Capecitabine has become a standard treatment option for metastatic breast cancer,
      as a single agent or in combination. Hand-foot syndrome and diarrhoea are the
      most frequently reported side effects, while capecitabine-related ileitis is very
      rare. Deficiency of dihydropyrimidine dehydrogenase activity leads to severe
      toxicities after administration of 5-fluorouracil or its prodrugs. We report two
      cases of patients with metastatic breast cancer who developed ileitis after
      treatment with capecitabine. One patient had a DPYD gene abnormality. 

PMID- 24748143
TI  - Hyperbilirubinaemia and haemolytic anaemia in acute alcoholic hepatitis: there's
      oil in them thar veins.
AB  - A Caucasian woman in her late 30s was evaluated after a period of binge drinking
      and found to have hyperbilirubinaemia for which she was referred for
      consideration of cholecystectomy. After exclusion of other possibilities, Zieve's
      syndrome was diagnosed. This is a condition of hyperbilirubinaemia, Coombs'
      negative haemolytic anaemia and hyperlipidaemia associated with alcoholism.
      Abstinence from alcohol remains the only known effective treatment, and
      appreciation of the entity can prevent unnecessary biliary procedures. The
      patient improved with supportive measures and was discharged in stable condition.

PMID- 24748144
TI  - Quadricuspid aortic valve: a rare congenital cardiac anomaly.

PMID- 24748145
TI  - Effect of BRMS1 on tumorigenicity and metastasis of human rectal cancer.
AB  - Breast cancer metastasis suppressor gene-1 (BRMS1) is newly discovered tumor
      metastasis gene, which has been reported to play an important role in the
      progression of human tumor. However, its role in rectal cancer has never been
      investigated. In this present study, we evaluated the associated of BRMS1 with
      colorectal cancer, its value in prognosis, and its role in metastasis of rectal
      cancer. BRMS1 expression examined in 80 patients and the role of BRMS1 in
      metastasis was studied using mice model. Our results showed that BRMS1 expression
      was significantly associated with clinicopathological parameters in rectal cancer
      patients and overexpression of BRMS1 in rectal cancer xenograft led to decreased
      growth, invasiveness and metastasis. Our findings indicate that high expression
      of BRSM1 in rectal cancer plays an essential role in tumor progression. 

PMID- 24748146
TI  - Myocardial dysfunction in early diabetes patients with microalbuminuria: a 2
      dimensional speckle tracking strain study.
AB  - The aim of this study was to assess myocardial dysfunction in primary diabetes
      patients with microalbuminuria by 2-dimensional speckle tracking strain. Sixty
      two patients with diabetes with or without hypertension and 37 matched
      hypertension controls were consecutively recruited from January 2011 to 2013.
      Routine physical examinations, laboratory tests, and echocardiography were
      performed in all patients. Subjects enrolled were divided into three groups
      according to history and urine albumin/creatinine ratio (ACR): group I: patients
      with only hypertension and normoalbuminuria (ACR < 30 mg/g), group II: patients
      with both hypertension and diabetes and normoalbuminuria (ACR < 30 mg/g), and
      group III: patients with both hypertension and diabetes and microalbuminuria (ACR
      30-300 mg/g). Echocardiographic images of three cardiac cycles were acquired for
      off-line analysis using the GE EchoPAC software. Indices of cardiac function,
      including longitudinal, radial and circumferential strains, torsion, and left
      ventricular ejection fraction (LVEF) were assessed. Statistical analysis was
      performed using SPSS 13.0. Finally, 56 subjects and 32 controls were included in
      the analyses. There was no significant difference in age, gender, heart rate,
      BMI, and LVEF among groups, except for the blood pressure, ACR, and HbA1c. E
      wave, A wave, EDT, E m, and E/E m in group III were different with those in group
      I. Mean longitudinal strain (mSL), average SL of six segments in 4-chamber apical
      view (SL4) decreased obviously. The peak circumferential strain decreased in
      group III, while the torsion was compensatively increased. ACR was negatively
      related to mSL, SL4, E/E m, and positively related to torsion. We deduced that
      ACR maybe a predictor for myocardial damage in primary diabetes.

PMID- 24748147
TI  - Shotgun pyrosequencing metagenomic analyses of dusts from swine confinement and
      grain facilities.
AB  - Inhalation of agricultural dusts causes inflammatory reactions and symptoms such
      as headache, fever, and malaise, which can progress to chronic airway
      inflammation and associated diseases, e.g. asthma, chronic bronchitis, chronic
      obstructive pulmonary disease, and hypersensitivity pneumonitis. Although in many
      agricultural environments feed particles are the major constituent of these
      dusts, the inflammatory responses that they provoke are likely attributable to
      particle-associated bacteria, archaebacteria, fungi, and viruses. In this study,
      we performed shotgun pyrosequencing metagenomic analyses of DNA from dusts from
      swine confinement facilities or grain elevators, with comparisons to dusts from
      pet-free households. DNA sequence alignment showed that 19% or 62% of shotgun
      pyrosequencing metagenomic DNA sequence reads from swine facility or household
      dusts, respectively, were of swine or human origin, respectively. In contrast
      only 2% of such reads from grain elevator dust were of mammalian origin. These
      metagenomic shotgun reads of mammalian origin were excluded from our analyses of
      agricultural dust microbiota. The ten most prevalent bacterial taxa identified in
      swine facility compared to grain elevator or household dust were comprised of
      75%, 16%, and 42% gram-positive organisms, respectively. Four of the top five
      swine facility dust genera were assignable (Clostridium, Lactobacillus,
      Ruminococcus, and Eubacterium, ranging from 4% to 19% relative abundance). The
      relative abundances of these four genera were lower in dust from grain elevators
      or pet-free households. These analyses also highlighted the predominance in swine
      facility dust of Firmicutes (70%) at the phylum level, Clostridia (44%) at the
      Class level, and Clostridiales at the Order level (41%). In summary, shotgun
      pyrosequencing metagenomic analyses of agricultural dusts show that they differ
      qualitatively and quantitatively at the level of microbial taxa present, and that
      the bioinformatic analyses used for such studies must be carefully designed to
      avoid the potential contribution of non-microbial DNA, e.g. from resident
      mammals. 

PMID- 24748148
TI  - Diagnostic value of osteoporosis self-assessment tool for Asians (OSTA) and
      quantitative bone ultrasound (QUS) in detecting high-risk populations for
      osteoporosis among elderly Chinese men.
AB  - This study aims to evaluate an osteoporosis self-assessment tool for Asians
      (OSTA) and quantitative bone ultrasound (QUS) and their combination in detecting
      populations at high risk for osteoporosis, and to determine the best cutoff value
      for the diagnosis of osteoporosis among elderly Chinese men. A group of Chinese
      men, aged >= 60 years, recruited from the health checkup population of Zhongshan
      Hospital, Fudan University, were included. The OSTA index was calculated from age
      and weight. Bone mineral density (BMD) at left hip (femoral neck, internal, and
      total hip) and lumbar spine (L1-L4, L-Total) was measured with dual-energy X-ray
      absorptiometry (DXA), and calcaneal BMD was measured with QUS. Receiver operating
      characteristic analysis was used to determine the best cutoff values,
      sensitivity, and specificity. The area under the curve (AUC) between the
      different screening tools was compared. Our study included 472 men with mean age
      of 78.0 years. The prevalence of osteoporosis was 27.7%.The best cutoff for OSTA
      was -3.5 for predicting men with osteoporosis at any site; this yielded a
      sensitivity and specificity of 47.3% and 76.8%, respectively. The AUC for OSTA
      was 0.676. The optimal cutoff for QUS-T score was -1.25, with a sensitivity of
      80.4% and specificity of 59.7%. The AUC for QUS-T score was 0.762. Combining QUS
      with OSTA improved the specificity to 92.9% but reduced sensitivity to 36.1%. A
      new variable derived from a combination of OSTA and the QUS-T score gave a better
      performance, with sensitivity of 70.1% and specificity of 72.1%; the AUC for this
      variable was 0.771, which was greater than OSTA but not different from QUS alone.
      In conclusion, OSTA and QUS, respectively, and their combination may help find
      populations at high risk for osteoporosis, which could be an alternative method
      for diagnosing osteoporosis, especially in areas where DXA measurement is not
      accessible.

PMID- 24748149
TI  - Decitabine of reduced dosage in Chinese patients with myelodysplastic syndrome: a
      retrospective analysis.
AB  - Decitabine has been approved for the treatment of all subtypes of myelodysplastic
      syndrome (MDS). However, the optimal regimen for decitabine treatment is not well
      established. In this study, an observational, retrospective and multi-center
      analysis was performed to explore the decitabine schedule for the treatment of
      MDS. A total of 79 patients received reduced dosage decitabine treatment (15
      mg/M2/day intravenously for five consecutive days every four weeks). Fifty-three
      out of the 79 patients were defined as intermediate-2/high risk by international
      prognostic scoring system (IPSS) risk category. 67.1% of MDS patients achieved
      treatment response including complete response (CR) (n = 23), Partial response (n
      = 1), marrow CR (mCR) with hematological improvement (HI) (n = 11), mCR without
      HI (n = 11) and HI alone (n = 7) with a median of 4 courses (range 1-11). The
      median overall survival (OS) was 18.0 months. The median OS was 22.0, 17.0 and
      12.0 months in the patients with CR, those with other response, and those without
      response, respectively. In addition, this regimen contributed to zero therapy
      related death and punctual course delivery, although III or IV grade of cytopenia
      was frequently observed. In conclusion, the 15 mg/M2/d*5 day decitabine regimen
      was effective and safe for Chinese MDS patients with IPSS score of 0.5 or higher.

PMID- 24748150
TI  - The influence of body position on cerebrospinal fluid pressure gradient and
      movement in cats with normal and impaired craniospinal communication.
AB  - Intracranial hypertension is a severe therapeutic problem, as there is
      insufficient knowledge about the physiology of cerebrospinal fluid (CSF)
      pressure. In this paper a new CSF pressure regulation hypothesis is proposed.
      According to this hypothesis, the CSF pressure depends on the laws of fluid
      mechanics and on the anatomical characteristics inside the cranial and spinal
      space, and not, as is today generally believed, on CSF secretion, circulation and
      absorption. The volume and pressure changes in the newly developed CSF model,
      which by its anatomical dimensions and basic biophysical features imitates the
      craniospinal system in cats, are compared to those obtained on cats with and
      without the blockade of craniospinal communication in different body positions.
      During verticalization, a long-lasting occurrence of negative CSF pressure inside
      the cranium in animals with normal cranio-spinal communication was observed. CSF
      pressure gradients change depending on the body position, but those gradients do
      not enable unidirectional CSF circulation from the hypothetical site of secretion
      to the site of absorption in any of them. Thus, our results indicate the
      existence of new physiological/pathophysiological correlations between
      intracranial fluids, which opens up the possibility of new therapeutic approaches
      to intracranial hypertension. 

PMID- 24748151
TI  - Field assessment of the predation risk-food availability trade-off in crab
      megalopae settlement.
AB  - Settlement is a key process for meroplanktonic organisms as it determines
      distribution of adult populations. Starvation and predation are two of the main
      mortality causes during this period; therefore, settlement tends to be optimized
      in microhabitats with high food availability and low predator density.
      Furthermore, brachyuran megalopae actively select favorable habitats for
      settlement, via chemical, visual and/or tactile cues. The main objective in this
      study was to assess the settlement of Metacarcinus edwardsii and Cancer plebejus
      under different combinations of food availability levels and predator presence.
      We determined, in the field, which factor is of greater relative importance when
      choosing a suitable microhabitat for settling. Passive larval collectors were
      deployed, crossing different scenarios of food availability and predator
      presence. We also explore if megalopae actively choose predator-free substrates
      in response to visual and/or chemical cues. We tested the response to combined
      visual and chemical cues and to each individually. Data was tested using a two
      way factorial design ANOVA. In both species, food did not cause significant
      effect on settlement success, but predator presence did, therefore there was not
      trade-off in this case and megalopae respond strongly to predation risk by active
      aversion. Larvae of M. edwardsii responded to chemical and visual cues
      simultaneously, but there was no response to either cue by itself. Statistically,
      C. plebejus did not exhibit a differential response to cues, but reacted with a
      strong similar tendency as M. edwardsii. We concluded that crab megalopae
      actively select predator-free microhabitat, independently of food availability,
      using chemical and visual cues combined. The findings in this study highlight the
      great relevance of predation on the settlement process and recruitment of marine
      invertebrates with complex life cycles. 

PMID- 24748152
TI  - Fission yeast Rad52 phosphorylation restrains error prone recombination pathways.
AB  - Rad52 is a key protein in homologous recombination (HR), a DNA repair pathway
      dedicated to double strand breaks and recovery of blocked or collapsed
      replication forks. Rad52 allows Rad51 loading on single strand DNA, an event
      required for strand invasion and D-loop formation. In addition, Rad52 functions
      also in Rad51 independent pathways because of its ability to promote single
      strand annealing (SSA) that leads to loss of genetic material and to promote D
      loops formation that are cleaved by Mus81 endonuclease. We have previously
      reported that fission yeast Rad52 is phosphorylated in a Sty1 dependent manner
      upon oxidative stress and in cells where the early step of HR is impaired because
      of lack of Rad51. Here we show that Rad52 is also constitutively phosphorylated
      in mus81 null cells and that Sty1 partially impinges on such phosphorylation. As
      upon oxidative stress, the Rad52 phosphorylation in rad51 and mus81 null cells
      appears to be independent of Tel1, Rad3 and Cdc2. Most importantly, we show that
      mutating serine 365 to glycine (S365G) in Rad52 leads to loss of the constitutive
      Rad52 phosphorylation observed in cells lacking Rad51 and to partial loss of
      Rad52 phosphorylation in cells lacking Mus81. Contrariwise, phosphorylation of
      Rad52-S365G protein is not affected upon oxidative stress. These results indicate
      that different Rad52 residues are phosphorylated in a Sty1 dependent manner in
      response to these distinct situations. Analysis of spontaneous HR at direct
      repeats shows that mutating serine 365 leads to an increase in spontaneous
      deletion-type recombinants issued from mitotic recombination that are Mus81
      dependent. In addition, the recombination rate in the rad52-S365G mutant is
      further increased by hydroxyurea, a drug to which mutant cells are sensitive. 

PMID- 24748153
TI  - Is exenatide the next big thing in Parkinson's disease?
AB  - A recent study by Aviles-Olmos and colleagues suggests that 12 months of
      treatment with the glucagon-like peptide-1 receptor agonist exenatide improves
      motor and cognitive symptoms in Parkinson's disease (PD), and that the effect
      persists as long as 12 months after termination of the treatment. Due to the lack
      of a placebo control, one cannot exclude that the observed differences between
      patients receiving daily injections of exenatide and non-treated controls are due
      to a placebo effect. We discuss that large group differences in two independent
      functional measures remain for at least 12 months following the cessation of
      exenatide treatment and that this warrants a double-blind placebo-controlled
      trial with exenatide in PD. 

PMID- 24748155
TI  - Ground layer plant species turnover and beta diversity in southern-European old
      growth forests.
AB  - Different assembly processes may simultaneously affect local-scale variation of
      species composition in temperate old-growth forests. Ground layer species
      diversity reflects chance colonization and persistence of low-dispersal species,
      as well as fine-scale environmental heterogeneity. The latter depends on both
      purely abiotic factors, such as soil properties and topography, and factors
      primarily determined by overstorey structure, such as light availability.
      Understanding the degree to which plant diversity in old-growth forests is
      associated with structural heterogeneity and/or to dispersal limitation will help
      assessing the effectiveness of silvicultural practices that recreate old-growth
      patterns and structures for the conservation or restoration of plant diversity.
      We used a nested sampling design to assess fine-scale species turnover, i.e. the
      proportion of species composition that changes among sampling units, across 11
      beech-dominated old-growth forests in Southern Europe. For each stand, we also
      measured a wide range of environmental and structural variables that might
      explain ground layer species turnover. Our aim was to quantify the relative
      importance of dispersal limitation in comparison to that of stand structural
      heterogeneity while controlling for other sources of environmental heterogeneity.
      For this purpose, we used multiple regression on distance matrices at the within
      stand extent, and mixed effect models at the extent of the whole dataset. Species
      turnover was best predicted by structural and environmental heterogeneity,
      especially by differences in light availability and in topsoil nutrient
      concentration and texture. Spatial distances were significant only in four out of
      eleven stands with a relatively low explanatory power. This suggests that
      structural heterogeneity is a more important driver of local-scale ground layer
      species turnover than dispersal limitation in southern European old-growth beech
      forests. 

PMID- 24748156
TI  - Similar metabolic changes induced by HIPVs exposure as herbivore in
      Ammopiptanthus mongolicus.
AB  - Herbivore-induced plant volatiles (HIPVs) are important compounds to prim
      neighboring undamaged plants; however, the mechanism for this priming process
      remains unclear. To reveal metabolic changes in plants exposed to HIPVs,
      metabolism of leaves and roots of Ammopiptanthus mongolicus seedlings exposed to
      HIPVs released from conspecific plants infested with larvae of Orgyia ericae were
      analyzed together with control and infested seedlings using nuclear magnetic
      resonance (NMR)-based metabolic technology and multi variate data analysis.
      Results presented showed that HIPVs exposure led to similar but specific
      metabolic changes compared with those induced by infestation in both leaves and
      roots. Furthermore, both HIPVs exposure and herbivore attack resulted in
      metabolic changes involving a series of primary and secondary metabolites in both
      leaves and roots. Taken together, these results suggested that priming of yet
      damaged plants may be achieved by reconfiguring metabolic pathways in leaves and
      roots to make similar concentrations for all metabolites as those in seedlings
      infested. Therefore, we propose that improved readiness of defense induction of
      primed plants toward subsequent herbivore attack may be based on the similar
      metabolic profiling induced by HIPVs exposure as those caused by herbivore. 

PMID- 24748157
TI  - Are fire, soil fertility and toxicity, water availability, plant functional
      diversity, and litter decomposition related in a Neotropical savanna?
AB  - Understanding how biodiversity and ecosystem functioning respond to changes in
      the environment is fundamental to the maintenance of ecosystem function. In
      realistic scenarios, the biodiversity-ecosystem functioning path may account for
      only a small share of all factors determining ecosystem function. Here, we
      investigated the strength to which variations in environmental characteristics in
      a Neotropical savanna affected functional diversity and decomposition. We sought
      an integrative approach, testing a number of pairwise hypotheses about how the
      environment, biodiversity, and functioning were linked. We used structural
      equation modelling to connect fire frequency, soil fertility, exchangeable Al,
      water availability, functional diversity of woody plants, tree density, tree
      height, and litter decomposition rates in a causal chain. We found significant
      effects of soil nutrients, water availability, and Al on functional diversity and
      litter decomposition. Fire did not have a significant direct effect on functional
      diversity or litter decomposition. However, fire was connected to both variables
      through soil fertility. Functional diversity did not influence rates of litter
      decomposition. The mediated effects that emerged from pairwise interactions are
      encouraging not only for predicting the functional consequences of changes in
      environmental variables and biodiversity, but also to caution against predictions
      based on only environmental or only biodiversity change. 

PMID- 24748158
TI  - The utility of secretin-enhanced MRCP in diagnosing congenital anomalies.
AB  - PURPOSE: To assess the additional value of secretin-enhanced MRCP (SMRCP) over
      conventional MRCP in diagnosing divisum. METHODS: Retrospective HIPAA-compliant
      and IRB-approved review found 140 patients with SMRCP and ERCP correlation within
      6 months of each other. All studies were anonymized and the SMRCP images (SMRCP
      image set) were separated from 2D and 3D MRCP and axial and coronal T2-weighted
      images (conventional MRI image set). Each image set on each patient was assigned
      different and randomized case numbers. Two reviewers (R1 and R2) independently
      reviewed the image sets for divisum vs. no divisum, complete divisum vs.
      incomplete divisum, and the certainty of diagnosis (1 = definitely certain, 2 =
      moderately certain, and 3 = unsure). ERCP findings were taken as gold standard.
      RESULTS: There was no difference in age and gender between the divisum (n = 97,
      with 13 incomplete divisum) and no divisum (n = 43) groups. In diagnosing divisum
      anatomy, the sensitivity was higher for SMRCP compared to conventional MRI for R1
      (84.5 vs. 72.2, p = 0.02) but not R2 (89.7 vs. 84.4, p = 0.25). The specificity
      was higher in SMRCP image set compared to conventional MRI (R1: 88.1 vs. 76.2, p
      = 0.01; R2: 81.4 vs. 65.1, p < 0.001). The mean area under ROC curve was higher
      for SMRCP image set (R1: 0.86 vs. 0.74, p = 0.01; R2: 0.87 vs. 0.74, p = 0.01).
      The certainty of diagnosis was higher in SMRCP image set compared to conventional
      MRI (p = 0.02 for both reviewers). SMRCP was not found to be superior in
      distinguishing incomplete from complete divisum. The main reasons for erroneous
      SMRCP diagnosis were the presence of an ansa loop in the main duct and ductal
      strictures due to chronic pancreatitis. CONCLUSION: Even though the reviewers had
      more sequences (axial and coronal) to evaluate in the non-secretin image set,
      there was some improvement in diagnosing divisum with SMRCP.

PMID- 24748159
TI  - Men traveling away from home are more likely to bring malaria into high altitude
      villages, northwest Ethiopia.
AB  - BACKGROUND: Information about malaria risk factors at high altitudes is scanty.
      Understanding the risk factors that determine the risk of malaria transmission at
      high altitude villages is important to facilitate implementing sustainable
      malaria control and prevention programs. METHODS: An unmatched case control study
      was conducted among patients seeking treatment at health centers in high altitude
      areas. Either microscopy or rapid diagnostic tests were used to confirm the
      presence of plasmodium species. A generalized linear model was used to identify
      the predictors of malaria transmission in high altitude villages. RESULTS: Males
      (AOR = 3.11, 95%CI: 2.28, 4.23), and those who traveled away from the home in the
      previous month (AOR = 2.01, 95% CI: 1.56, 2.58) were strongly associated with
      presence of malaria in high altitude villages. Other significant factors,
      including agriculture in occupation (AOR = 1.41, 95% CI: 1.05, 1.93), plants used
      for fencing (AOR = 1.70, 95% CI: 1.18, 2.52) and forests near the house (AOR =
      1.60, 95% CI: 1.15, 2.47), were found predictors for malaria in high altitude
      villages. CONCLUSION: Travel outside of their home was an important risk of
      malaria infections acquisition. Targeting males who frequently travel to
      malarious areas can reduce malaria transmission risks in high altitude areas.

PMID- 24748154
TI  - The cost-effectiveness of wound-edge protection devices compared to standard care
      in reducing surgical site infection after laparotomy: an economic evaluation
      alongside the ROSSINI trial.
AB  - BACKGROUND: Wound-edge protection devices (WEPDs) have been used in surgery for
      more than 40 years to reduce surgical site infection (SSI). No economic
      evaluation of WEPDs against any comparator has ever been conducted. The aim of
      the paper was to assess whether WEPDs are cost-effective in reducing SSI compared
      to standard care alone in the United Kingdom. METHODS AND FINDINGS: An economic
      evaluation was conducted alongside the ROSSINI trial. The study perspective was
      that of the UK National Health Service and the time horizon was 30 days post
      operatively. The study was conducted in 21 UK hospitals. 760 patients undergoing
      laparotomy were randomised to either WEPD or standard care and 735 were included
      in the primary analysis. The main economic outcome was cost-effectiveness based
      on incremental cost (L) per quality adjusted life year (QALY) gained. Patients in
      the WEPD arm accessed health care worth L5,420 on average and gained 0.02131
      QALYs, compared to L5,130 and 0.02133 QALYs gained in the standard care arm. The
      WEPD strategy was more costly and equally effective compared to standard care,
      but there was significant uncertainty around incremental costs and QALYs. The
      findings were robust to a range of sensitivity analyses. CONCLUSIONS: There is no
      evidence to suggest that WEPDs can be considered a cost effective device to
      reduce SSI. Their continued use is a waste of limited health care resources.

PMID- 24748161
TI  - Hospital and geographic variability in two colorectal cancer surgery outcomes:
      complications and mortality after complications.
AB  - BACKGROUND: The purpose of this study was to describe hospital and geographic
      variation in 30-day risk of surgical complications and death among colorectal
      cancer (CRC) patients and the extent to which patient-, hospital-, and census
      tract-level characteristics increased risk of these outcomes. METHODS: We
      included patients at least 66 years old with first primary stage I-III CRC from
      the 2000-2005 National Cancer Institute's Surveillance, Epidemiology, and End
      Results data linked with 1999-2005 Medicare claims. A multilevel, cross
      classified logistic model was used to account for nesting of patients within
      hospitals and within residential census tracts. Outcomes were risk of
      complications and death after a complication within 30 days of surgery. RESULTS:
      Data were analyzed for 35,946 patients undergoing surgery at 1,222 hospitals and
      residing in 12,187 census tracts; 27.2 % of patients developed complications, and
      of these 13.4 % died. Risk-adjusted variability in complications across hospitals
      and census tracts was similar. Variability in mortality was larger than
      variability in complications, across hospitals and across census tracts. Specific
      characteristics increased risk of complications (e.g., census-tract-poverty rate,
      emergency surgery, and being African-American). No hospital characteristics
      increased complication risk. Specific characteristics increased risk of death
      (e.g. census-tract-poverty rate, being diagnosed with colon (versus rectal)
      cancer, and emergency surgery), while hospitals with at least 500 beds showed
      reduced death risk. CONCLUSIONS: Large, unexplained variations exist in mortality
      after surgical complications in CRC across hospitals and geographic areas. The
      potential exists for quality improvement efforts targeted at the hospital and/or
      census-tract levels to prevent complications and augment hospitals' ability to
      reduce mortality risk.

PMID- 24748162
TI  - Quality of colorectal cancer care among veterans: a 10-year retrospective cohort.
AB  - BACKGROUND: Nearly 5,000 patients within Veterans Health Administration (VHA) are
      diagnosed with colorectal cancer (CRC) annually. However, the link between
      performance on CRC practice guidelines and outcomes is unclear. The purpose of
      this study was to evaluate quality of CRC care by assessing adherence to National
      Comprehensive Cancer Network (NCCN) guidelines and to determine if receipt of
      these metrics was associated with improvement in mortality. METHODS: We performed
      a retrospective cohort study of all patients who underwent resection for
      nonmetastatic CRC at VHA Tennessee Valley Healthcare System from 2001 to 2010. We
      defined "excellent" care as receipt of at least 75 % of eligible NCCN metrics. We
      also examined time to treatment and the relationship between excellent care and
      mortality. RESULTS: A total of 331 patients underwent resection for CRC within
      the study period. Only 47 % of patients received excellent care, and 9 % received
      100 % of eligible metrics. The median time from diagnosis to definitive treatment
      was 22 days [interquartile range (IQR) 12, 41] and 37 days (IQR 24, 56) among
      colon and rectal cancer patients, respectively. The likelihood of receiving
      excellent care increased significantly over time. However, there was no
      association between receipt of excellent care and 5-year all-cause mortality
      [hazard ratio (HR) 0.85; 95 % CI 0.53-1.36]. CONCLUSIONS: Although patients
      received timely care overall, fewer than half of CRC patients received at least
      75 % of eligible NCCN metrics. Although receipt of excellent care was not
      associated with reduction in all-cause mortality, further research is necessary
      to identify quality metrics likely to influence patient outcomes.

PMID- 24748163
TI  - Laparotomy conversion rate of laparoscopic radical hysterectomy for early-stage
      cervical cancer in a consecutive series without case selection.
AB  - PURPOSE: To estimate the feasibility and conversion rate of laparoscopic radical
      hysterectomy (LRH) in early-stage cervical cancer. METHODS: Data were collected
      from the medical records of 260 consecutive patients with stage IA2 to IIA2
      cervical cancer who had undergone LRH, regardless of age, body mass index, prior
      abdominal surgery, uterus size, or tumor size. RESULTS: The median patient age
      was 48 years (range, 26-78 years), 11.9 % of whom were elderly (>=65 years), 11.2
      % were obese (>=30 kg/m(2)), 15.4 % had undergone previous abdominal surgery, and
      13.1 % had a tumor larger than 4 cm. Negative-margin resection was feasible in
      all patients except one. The median operative time and estimated blood loss were
      253 min (range, 111-438 min) and 300 mL (range, 80-2000 mL), respectively.
      Intraoperative and postoperative complications occurred in seven (2.7 %) and 10
      patients (3.8 %), respectively. Four patients (1.5 %) required intraoperative
      conversion to laparotomy, three of which were due to conglomerated metastatic
      lymph nodes surrounding the aorta (n = 2), the left external iliac vein (n = 1)
      or the left ureter (n = 1). LRH was still completed in the four conversion
      patients, and a laparotomy was required for the removal of the conglomerated
      metastatic lymph nodes and the repair of the injured vessels. CONCLUSIONS: The
      conversion rate to laparotomy among patients undergoing LRH for early-stage
      cervical cancer was 1.5 % when performed exclusively in consecutive patients. LRH
      showed comparable feasibility and effectiveness to open radical hysterectomy in
      the treatment of early-stage cervical cancer.

PMID- 24748164
TI  - gamma-Glutamyltranspeptidase is a prognostic marker of survival and recurrence in
      radiofrequency-ablation treatment of hepatocellular carcinoma.
AB  - PURPOSE: Serum gamma-glutamyltranspeptidase (GGT) level, which is often elevated
      in hepatocellular carcinoma (HCC), has now been found to be an oxidative stress
      marker which correlates with inflammation in the extracellular hepatic
      microenvironment. The aim of this study was to investigate the prognostic
      significance of GGT serum levels in patients undergoing radiofrequency ablation
      (RFA) therapy for the treatment of HCC. METHODS: This retrospective study
      included 254 patients with small liver cancer (tumor of <=5 cm in diameter and
      nodule of <=3 cm) who had been treated with RFA. Baseline serum GGT was examined
      before therapy, and overall survival (OS) and recurrence-free survival were
      evaluated by the Kaplan-Meier method. Univariate and multivariate analyses were
      used to analyze the significance of GGT and other serum markers as prognostic
      factors. RESULTS: After a median follow-up of 27 months, 51 patients had died and
      123 had hepatic recurrence. After treatment with RFA, HCC patients with elevated
      GGT had a shorter OS versus those with normal GGT level (p = 0.001); they also
      had higher recurrence (p = 0.001). On multivariate analysis, albumin (p = 0.003),
      GGT (p = 0.035), and tumor size (p = 0.027) were independent risk factors for
      survival, and GGT (p = 0.010) and tumor size (p = 0.026) were significant risk
      factors for recurrence. CONCLUSIONS: Serum GGT is a convenient prognostic
      biomarker related to OS and recurrence in HCC patients undergoing RFA treatment.

PMID- 24748165
TI  - Bisphosphonates in the management of thalassemia-associated osteoporosis: a
      systematic review of randomised controlled trials.
AB  - Bisphosphonates are potent inhibitors of bone resorption, widely used for the
      management of osteoporosis and fracture prevention. Recent evidence suggests that
      bisphosphonates may have beneficial effects in the treatment of thalassemia
      associated osteoporosis, a complex and multifactorial condition. Here we
      summarise available data about the efficacy and tolerability of bisphosphonates
      in beta--thalassemic patients. Randomised controlled trials (RCTs) of
      bisphosphonates in beta-thalassemia were identified searching PubMed. Studies
      were reviewed to retrieve relevant clinical information. The following variables
      were considered to assess the safety and efficacy of bisphosphonates-bone mineral
      density (BMD), markers of bone turnover, incidence of fragility fracture, bone
      pain, back pain, and clinical adverse events. Five RCTs were identified,
      investigating alendronate, clodronate, zoledronic acid and neridronate. All
      bisphosphonates produced a significant decrease of the markers of bone turnover.
      Alendronate, neridronate, and zoledronic acid significantly improved BMD at the
      lumbar spine, femoral neck and total hip. Zoledronic acid and neridronate were
      also shown to reduce bone and back pain. Probably due to the small sample sizes
      and to the short duration of the trials, it was not possible to establish the
      anti-fracture efficacy of bisphosphonates; however, they were well tolerated and
      adverse events were rare but expected on the basis of previous studies.
      Sufficient evidence exists to support the use of bisphosphonates in the
      management of thalassemia-associated osteoporosis (to prevent bone loss and
      improve the BMD). Further research is warranted to establish their anti-fracture
      efficacy and long-term safety.

PMID- 24748166
TI  - Acetobixan, an inhibitor of cellulose synthesis identified by microbial
      bioprospecting.
AB  - In plants, cellulose biosynthesis is an essential process for anisotropic growth
      and therefore is an ideal target for inhibition. Based on the documented utility
      of small-molecule inhibitors to dissect complex cellular processes we identified
      a cellulose biosynthesis inhibitor (CBI), named acetobixan, by bio-prospecting
      among compounds secreted by endophytic microorganisms. Acetobixan was identified
      using a drug-gene interaction screen to sift through hundreds of endophytic
      microbial secretions for one that caused synergistic reduction in root expansion
      of the leaky AtcesA6prc1-1 mutant. We then mined this microbial secretion for
      compounds that were differentially abundant compared with Bacilli that failed to
      mimic CBI action to isolate a lead pharmacophore. Analogs of this lead compound
      were screened for CBI activity, and the most potent analog was named acetobixan.
      In living Arabidopsis cells visualized by confocal microscopy, acetobixan
      treatment caused CESA particles localized at the plasma membrane (PM) to rapidly
      re-localize to cytoplasmic vesicles. Acetobixan inhibited 14C-Glc uptake into
      crystalline cellulose. Moreover, cortical microtubule dynamics were not disrupted
      by acetobixan, suggesting specific activity towards cellulose synthesis. Previous
      CBI resistant mutants such as ixr1-2, ixr2-1 or aegeus were not cross resistant
      to acetobixan indicating that acetobixan targets a different aspect of cellulose
      biosynthesis. 

PMID- 24748167
TI  - Short-term effect of antibiotics on human gut microbiota.
AB  - From birth onwards, the human gut microbiota rapidly increases in diversity and
      reaches an adult-like stage at three years of age. After this age, the
      composition may fluctuate in response to external factors such as antibiotics.
      Previous studies have shown that resilience is not complete months after
      cessation of the antibiotic intake. However, little is known about the short-term
      effects of antibiotic intake on the gut microbial community. Here we examined the
      load and composition of the fecal microbiota immediately after treatment in 21
      patients, who received broad-spectrum antibiotics such as fluoroquinolones and
      beta-lactams. A fecal sample was collected from all participants before treatment
      and one week after for microbial load and community composition analyses by
      quantitative PCR and pyrosequencing of the 16S rRNA gene, respectively.
      Fluoroquinolones and beta-lactams significantly decreased microbial diversity by
      25% and reduced the core phylogenetic microbiota from 29 to 12 taxa. However, at
      the phylum level, these antibiotics increased the Bacteroidetes/Firmicutes ratio
      (p = 0.0007, FDR = 0.002). At the species level, our findings unexpectedly
      revealed that both antibiotic types increased the proportion of several unknown
      taxa belonging to the Bacteroides genus, a Gram-negative group of bacteria (p =
      0.0003, FDR<0.016). Furthermore, the average microbial load was affected by the
      treatment. Indeed, the beta-lactams increased it significantly by two-fold (p =
      0.04). The maintenance of or possible increase detected in microbial load and the
      selection of Gram-negative over Gram-positive bacteria breaks the idea generally
      held about the effect of broad-spectrum antibiotics on gut microbiota. 

PMID- 24748168
TI  - Phylogenetic analysis of the endoribonuclease Dicer family.
AB  - Dicers are proteins of the ribonuclease III family with the ability to process
      dsRNA, involved in regulation of gene expression at the post-transcriptional
      level. Dicers are conserved from basal metazoans to higher metazoans and contain
      a number of functional domains that interact with dsRNA. The completed genome
      sequences of over 34 invertebrate species allowed us to systematically
      investigate Dicer genes over a diverse range of phyla. The majority of
      invertebrate Dicers clearly fell into the Dicer1 or Dicer2 subfamilies. Most
      nematodes possessed only one Dicer gene, a member of the Dicer1 subfamily,
      whereas two Dicer genes (Dicer1 and Dicer2) were present in all platyhelminths
      surveyed. Analysis of the key domains showed that a 5' pocket was conserved
      across members of the Dicer1 subfamily, with the exception of the nematode
      Bursaphelenchus xylophilus. Interestingly, Nematostella vectensis DicerB grouped
      into Dicer2 subfamily harbored a 5' pocket, which is commonly present in Dicer1.
      Similarly, the 3' pocket was also found to be conserved in all Dicer proteins
      with the exceptions of Schmidtea mediterranea Dicer2 and Trichoplax adherens
      Dicer A. The loss of catalytic residues in the RNase III domain was noted in
      platyhelminths and cnidarians, and the 'ball' and 'socket' junction between two
      RNase III domains in platyhelminth Dicers was different from the canonical
      junction, suggesting the possibility of different conformations. The present data
      suggest that Dicers might have duplicated and diversified independently, and have
      evolved for various functions in invertebrates. 

PMID- 24748170
TI  - Capsaicin treatment attenuates cholangiocarcinoma carcinogenesis.
AB  - Capsaicin, the most abundant pungent molecule produced by pepper plants,
      represents an important ingredient in spicy foods consumed throughout the world.
      Studies have shown that capsaicin can relieve inflammation and has anti
      proliferative effects on various human malignancies. Cholangiocarcinoma (CC) is a
      cancer disease with rising incidence. The prognosis remains dismal with little
      advance in treatment. The aim of the present study is to explore the anti-tumor
      activity of capsaicin in cultured human CC cell lines. Capsaicin effectively
      impaired cell proliferation, migration, invasion, epithelial to mesenchymal
      transition and growth of softagar colonies. Further, we show that capsaicin
      treatment of CC cells regulates the Hedgehog signaling pathway. CONCLUSION: Our
      results provide a basis for capsaicin to improve the prognosis of CCs in vivo and
      present new insights into the effectiveness and mode of action of capsaicin.

PMID- 24748171
TI  - Towards an integrative structural biology approach: combining Cryo-TEM, X-ray
      crystallography, and NMR.
AB  - Cryo-transmission electron microscopy (Cryo-TEM) and particularly single particle
      analysis is rapidly becoming the premier method for determining the three
      dimensional structure of protein complexes, and viruses. In the last several
      years there have been dramatic technological improvements in Cryo-TEM, such as
      advancements in automation and use of improved detectors, as well as improved
      image processing techniques. While Cryo-TEM was once thought of as a low
      resolution structural technique, the method is currently capable of generating
      nearly atomic resolution structures on a routine basis. Moreover, the combination
      of Cryo-TEM and other methods such as X-ray crystallography, nuclear magnetic
      resonance spectroscopy, and molecular dynamics modeling are allowing researchers
      to address scientific questions previously thought intractable. Future
      technological developments are widely believed to further enhance the method and
      it is not inconceivable that Cryo-TEM could become as routine as X-ray
      crystallography for protein structure determination. 

PMID- 24748172
TI  - Orexin-A promotes cell migration in cultured rat astrocytes via Ca2+-dependent
      PKCalpha and ERK1/2 signals.
AB  - Orexin-A is an important neuropeptide involved in the regulation of feeding,
      arousal, energy consuming, and reward seeking in the body. The effects of orexin
      A have widely studied in neurons but not in astrocytes. Here, we report that OX1R
      and OX2R are expressed in cultured rat astrocytes. Orexin-A stimulated the
      phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2), and then
      induced the migration of astrocytes via its receptor OX1R but not OX2R. Orexin-A
      induced ERK1/2 phosphorylation and astrocytes migration are Ca2+-dependent, since
      they could be inhibited by either chelating the extracellular Ca2+ or blocking
      the pathway of store-operated calcium entry (SOCE). Furthermore, both non
      selective protein kinase C (PKC) inhibitor and PKCalpha selective inhibitor, but
      not PKCdelta inhibitor, prevented the increase in ERK1/2 phosphorylation and the
      migration of astrocytes, indicating that the Ca2+-dependent PKCalpha acts as the
      downstream of the OX1R activation and mediates the orexin-A-induced increase in
      ERK1/2 phosphorylation and cell migration. In conclusion, these results suggest
      that orexin-A can stimulate ERK1/2 phosphorylation and then facilitate the
      migration of astrocytes via PLC-PKCalpha signal pathway, providing new knowledge
      about the functions of the OX1R in astrocytes. 

PMID- 24748173
TI  - Global gene expression analysis of canine cutaneous mast cell tumor: could
      molecular profiling be useful for subtype classification and prognostication?
AB  - Prognosis and therapeutic management of dogs with cutaneous mast cell tumors
      (MCTs) depend on clinical stage and histological grade. However, the prognostic
      value of this latter is still questionable. In the present study, MCT
      transcriptome was analyzed to identify a set of candidate genes potentially
      useful for predicting the biological behavior of MCTs. Fifty-one canine MCT
      biopsies were analyzed. Isolated and purified total RNAs were individually
      hybridized to the Agilent Canine V2 4x44k DNA microarray. The comparison of
      reference differentiated and undifferentiated MCT transcriptome revealed a total
      of 597 differentially expressed genes (147 down-regulated and 450 up-regulated).
      The functional analysis of this set of genes provided evidence that they were
      mainly involved in cell cycle, DNA replication, p53 signaling pathway, nucleotide
      excision repair and pyrimidine metabolism. Class prediction analysis identified
      13 transcripts providing the greatest accuracy of class prediction and divided
      samples into two categories (differentiated and undifferentiated), harboring a
      different prognosis. The Principal Component Analysis of all samples, made by
      using the selected 13 markers, confirmed MCT classification. The first three
      components accounted for 99.924% of the total variance. This molecular
      classification significantly correlated with survival time (p = 0.0026).
      Furthermore, among all marker genes, a significant association was found between
      mRNA expression and MCT-related mortality for FOXM1, GSN, FEN1 and KPNA2
      (p<0.05). Finally, marker genes mRNA expression was evaluated in a cohort of 22
      independent samples. Data obtained enabled to identify MCT cases with different
      prognosis. Overall, the molecular characterization of canine MCT transcriptome
      allowed the identification of a set of 13 transcripts that clearly separated
      differentiated from undifferentiated MCTs, thus predicting outcome regardless of
      the histological grade. These results may have clinical relevance and warrant
      future validation in a prospective study. 

PMID- 24748174
TI  - HIV-1 Nef inhibits Protease activity and its absence alters protein content of
      mature viral particles.
AB  - Nef is an important player for viral infectivity and AIDS progression, but the
      mechanisms involved are not completely understood. It was previously demonstrated
      that Nef interacts with GagPol through p6*-Protease region. Because p6* and
      Protease are involved in processing, we explored the effect of Nef on viral
      Protease activity and virion assembly. Using in vitro assays, we observed that
      Nef is highly capable of inhibiting Protease activity. The IC50 for nef-deficient
      viruses in drug susceptibility assays were 1.7- to 3.5-fold higher than the wild
      type counterpart varying with the type of the Protease inhibitor used. Indicating
      that, in the absence of Nef, Protease is less sensitive to Protease inhibitors.
      We compared the protein content between wild-type and nef-deficient mature viral
      particles by gradient sedimentation and observed up to 2.7-fold reduction in the
      Integrase levels in nef-deficient mature particles. This difference in levels of
      Integrase correlated with the difference in infectivity levels of wild type and
      nef-deficient viral progeny. In addition, an overall decrease in the production
      of mature particles was detected in nef-deficient viruses. Collectively, our data
      support the hypothesis that the decreased infectivity typical of nef-deficient
      viruses is due to an abnormal function of the viral Protease, which is in turn
      associated with less mature particles being produced and the loss of Integrase
      content in these particles, and these results may characterize Nef as a regulator
      of viral Protease activity. 

PMID- 24748176
TI  - Effects of adaptive support ventilation and synchronized intermittent mandatory
      ventilation on peripheral circulation and blood gas markers of COPD patients with
      respiratory failure.
AB  - The objective of the study was to investigate the effects of adaptive support
      ventilation (ASV) and synchronized intermittent mandatory ventilation (SIMV) on
      peripheral circulation of chronic obstructive pulmonary disease (COPD) patients
      with respiratory failure. 86 COPD patients with respiratory failure were
      recruited in this study. Self-control method was used to compare the effect of
      ASV and SIMV on the parameters of ventilation machine, heart rate, blood
      pressure, central venous pressure (CVP), and blood gas markers. When the patients
      in ASV and SIMV groups were compared, respiratory rate, tidal volume, and peak
      airway pressure (PIP) showed significant difference. When minute ventilation (MV)
      was compared, no significant difference was shown. When peripheral circulation
      parameters were compared, peripheral circulation heart rate, SBP, DBP, and CVP
      showed significant difference. Compared with SIMV group, PaO2, pH, and SaO2
      values were remarkably increased (P < 0.01) while no significant difference was
      found for partial pressure of carbon dioxide (pCO2) when two groups were
      compared. In conclusion, when mechanical ventilation was used in COPD patients
      with respiratory failure, ASV can significantly improve clinical outcomes.

PMID- 24748175
TI  - Highly specific contractions of a single CAG/CTG trinucleotide repeat by TALEN in
      yeast.
AB  - Trinucleotide repeat expansions are responsible for more than two dozens severe
      neurological disorders in humans. A double-strand break between two short CAG/CTG
      trinucleotide repeats was formerly shown to induce a high frequency of repeat
      contractions in yeast. Here, using a dedicated TALEN, we show that induction of a
      double-strand break into a CAG/CTG trinucleotide repeat in heterozygous yeast
      diploid cells results in gene conversion of the repeat tract with near 100%
      efficacy, deleting the repeat tract. Induction of the same TALEN in homozygous
      yeast diploids leads to contractions of both repeats to a final length of 3-13
      triplets, with 100% efficacy in cells that survived the double-strand breaks.
      Whole-genome sequencing of surviving yeast cells shows that the TALEN does not
      increase mutation rate. No other CAG/CTG repeat of the yeast genome showed any
      length alteration or mutation. No large genomic rearrangement such as aneuploidy,
      segmental duplication or translocation was detected. It is the first
      demonstration that induction of a TALEN in an eukaryotic cell leads to shortening
      of trinucleotide repeat tracts to lengths below pathological thresholds in
      humans, with 100% efficacy and very high specificity. 

PMID- 24748177
TI  - Comparative effects of hispidulin, genistein, and icariin with estrogen on bone
      tissue in ovariectomized rats.
AB  - Icariin, Genistein, and Hispidulin have been proven to have estrogen-like and
      antiosteoporotic activity and can be potentially used for the treatment of
      osteoporosis. The present study found that Icariin, Genistein, and Hispidulin
      treatments, emulating estrogen, significantly contributed to bone density.
      Comparative effects of Icariin, Genistein, and Hispidulin with estrogen on in
      ovariectomized rats were investigated. Our results showed that genistein was
      found to have superior bone protective effects against osteoporosis among
      genistein, Icariin, and Hispidulin. 

PMID- 24748178
TI  - Negative-pressure wound therapy enhances local inflammatory responses in acute
      infected soft-tissue wound.
AB  - Clinical studies found that negative-pressure wound therapy (NPWT) displayed
      significant clinical benefits in the healing of infected wounds. However, the
      effect of NPWT on local inflammatory responses in acute infected soft-tissue
      wound has not been investigated thoroughly. The purpose of this study was to test
      the impact of NPWT on local expression of proinflammatory cytokines, amount of
      neutrophils, and bacterial bioburden in wound from acute infected soft-tissue
      wounds. Full-thickness wounds were created on the back of rabbits, and were
      inoculated with Staphylococcus aureus strain ATCC29213. The wounds were treated
      with sterile saline-moistened gauze dressings and NPWT with continuous negative
      pressure (-125 mmHg). Wound samples were harvested on days 0 (6 h after bacterial
      inoculation), 2, 4, 6, and 8 at the center of wound beds before irrigation for
      real-time PCR analysis of gene expression of IL-1beta, IL-8, and TNF-alpha. Wound
      biopsies were examined histologically for neutrophil quantification in different
      layers of tissue. Quantitative bacterial cultures at the same time point were
      analyzed for bacterial clearance. Application of NPWT to acute infected wounds in
      rabbits was compared with treatment with sterile saline-moistened gauze, over an
      8-day period. NPWT-treated wounds exhibited earlier and greater peaking of IL
      1beta and IL-8 expression and decrease in TNF-alpha expression over the early 4
      days (P < 0.05). Furthermore, histologic examination revealed that significantly
      increased neutrophil count was observed in the shallow layer in wound biopsies of
      NPWT treatment at day 2 (P < 0.001). In addition, there was a statistically
      significant decrease of bacteria load from baseline (day 0) at days 2 and 8 in
      NPWT group (P < 0.05). In conclusion, this study demonstrates that NPWT of acute
      infected soft-tissue wounds leads to increased local IL-1beta and IL-8 expression
      in early phase of inflammation, which may trigger accumulation of neutrophils and
      thus accelerate bacterial clearance. Meanwhile, the success of NPWT in the
      treatment of acute wounds can attenuate the expression of TNF-alpha, and the
      result may partly explain how NPWT can avoid significantly impairing wound
      healing.

PMID- 24748179
TI  - Randomized clinical trial comparing ultrasound-guided procedure with the
      Seldinger's technique for placement of implantable venous ports.
AB  - The aim of this randomized controlled study was to compare ultrasound-guided
      procedure with the Seldinger's technique for placement of implantable venous
      ports. A total of 214 patients were randomized to receive TIAP placement by
      either ultrasound-guided procedure or the Seldinger's technique. Complications
      and pain perception were compared between these two groups. No severe
      perioperative or periinterventional complication occurred. Significantly (P <
      0.05) lower pain perception was observed in the ultrasound-guided group.
      Seldinger's technique group showed higher rate in incidence of early and late
      complications including catheter dislocation, catheter occlusion, venous
      thrombosis, fever of unknown origin, skin necrosis, and sepsis. In conclusion,
      both techniques, the TIAP implantation via ultrasound-guided jugular vein
      puncture and via Seldinger's technique subclavian vein puncture, are feasible and
      safe. Regarding intrainterventional pain perception and implantation-related
      complications, the jugular vein puncture under ultrasound guidance seems to be
      advantageous.

PMID- 24748180
TI  - Ecto-mesenchymal stem cells from facial process: potential for muscle
      regeneration.
AB  - Ecto-mesenchymal stem cells (EMSCs) originate from the cranial neural crest and
      participate in the formation of tooth, salivary, and muscle in early development
      stage. The transplantation of EMSCs, a potential source of myoblast stem cell,
      might improve muscle regeneration. The purpose of this study was to explore
      whether EMSCs have the potential to differentiate and display a myogenic
      phenotype in vitro the in vitro. Here, we characterized the EMSCs isolated from
      the facial process, and p75 + EMSCs were collected by a FACS calibur flow
      cytometer. In vitro, p75 + EMSCs induced by DMSO can accumulate and fuse into
      multinucleated myotubes and further differentiate into the skeletal muscle cells
      in form of cell sheet. Functional myoblast phenotypes of p75 + EMSCs were found
      in vivo model of muscle injury. The remarkable ability of stem cells to
      regenerate skeletal muscle indicated their potential role in the cell therapy and
      tissue engineering of the skeletal muscle.

PMID- 24748181
TI  - Retraction: improvement of landfill leachate biodegradability with ultrasonic
      process.

PMID- 24748182
TI  - Efficacy of transjugular intrahepatic portosystemic shunt with adjunctive
      embolotherapy with cyanoacrylate for esophageal variceal bleeding.
AB  - BACKGROUND: Transjugular intrahepatic portosystemic shunt (TIPS) with adjunctive
      embolotherapy has recently been reported to be effective in the prevention of
      variceal hemorrhage of cirrhotic patients. However, further investigation of its
      long-term efficacy is still needed. AIM: To examine the rebleeding, survival, and
      hepatic encephalopathy (HE) after treatment with TIPS alone and TIPS with
      adjunctive embolotherapy using cyanoacrylate for esophageal variceal bleeding.
      METHODS: Patients with refractory to endoscopic therapy for esophageal variceal
      bleeding were enrolled. TIPS was performed in 101 patients with adjunctive
      embolotherapy (n = 53) or alone (n = 48) between January 2006 and December 2011.
      Chart reviews were performed to determine rebleeding, survival rates, and the
      incidence of HE. RESULTS: Recurrent hemorrhage occurred in 12 (11.9 %) patients
      during the mean follow-up periods of 35.8 months. Rebleeding was observed in 9/48
      (18.8 %) patients in TIPS alone group and 3/53 (5.7 %) patients in TIPS with
      adjunctive embolotherapy group (p = 0.042). Death occurred in 30 patients during
      follow-up (TIPS alone: n = 16, TIPS with adjunctive embolotherapy: n = 14, p =
      0.447). Twenty-six episodes of HE occurred in 18 patients in TIPS alone group and
      16 episodes occurred in 10 patients in TIPS with embolotherapy group. The
      probability of HE was significantly higher in TIPS alone group than in TIPS with
      embolotherapy group (p = 0.019). CONCLUSIONS: TIPS with adjunctive embolotherapy
      with cyanoacrylate is relatively safe and effective, with a lower rebleeding and
      HE incidence in comparison of TIPS alone.

PMID- 24748183
TI  - Cholangiocarcinoma and high-grade dysplasia in young patients with primary
      sclerosing cholangitis.
AB  - INTRODUCTION: Cholangiocarcinoma (CCA) is very often an adulthood disease with
      primary sclerosing cholangitis (PSC) as one of the risk factors. It is rarely
      seen in the pediatric population, and when it is diagnosed before adulthood, it
      can be associated with PSC as well as HIV infection, biliary atresia, radiation
      therapy, and choledochal cyst. Although there have been some case reports of
      pediatric CCA, cases of childhood CCA associated with PSC are still relatively
      rare. AIM: To describe the clinical and pathologic features of CCA in pediatric
      patients with previously diagnosed PSC. METHODS: Retrospective study RESULTS:
      Four patients with PSC (age range 15-18, mean 17 years) were included in this
      study. All patients underwent ERCP for diagnosis. Tissue samples obtained
      included routine cytology and FISH. ERCP was used to target sites for tissue
      acquisition in all patients. 3/4 of patients have inflammatory bowel disease (two
      Crohn's disease and one ulcerative colitis). Alkaline phosphatase was elevated in
      3/4 patients, aspartate aminotransferase/alanine aminotransferase were elevated
      in 2/4 patients, and total bilirubin/direct bilirubin were elevated in 2/4
      patients. 4/4 patients had positive FISH studies, and 3/4 patients had brush
      cytology concerning for CCA. 2/4 patients received chemotherapy, one patient
      underwent orthotopic liver transplant, and one patient underwent Whipple
      procedure. Two patients died soon after being diagnosed. CONCLUSIONS: Young
      patients with PSC can develop CCA. This finding has implications for both
      screening and surveillance for cancer in pediatric patients with PSC.

PMID- 24748184
TI  - MicroRNA-194 inhibits the epithelial-mesenchymal transition in gastric cancer
      cells by targeting FoxM1.
AB  - AIM: We hypothesized that miR-194 may control Forkhead box protein M1 (FoxM1)
      expression in gastric cancer cells and therefore may have therapeutic potential
      in gastric cancer. METHODS: The expression level of miR-194 was examined using
      real-time PCR in human gastric cancer and noncancerous gastric tissues, gastric
      cancer cell and normal gastric mucosal epithelial cell. We examined whether the
      miR-194 regulates cell migration and invasion, and the epithelial-mesenchymal
      transition Phenotype by inhibiting FoxM1 in gastric cancer cells. RESULTS: The
      expression of miR-194 was significantly lower in gastric cancer compared with non
      cancerous gastric tissues and cells. Exogenous expression of miR-194 inhibited
      cell migration, invasion, and the epithelial-mesenchymal transition phenotype in
      gastric cancer cells. Moreover, we discovered a novel post-transcriptional
      regulatory mechanism of FoxM1 expression that is mediated by miR-194. CONCLUSION:
      Our study clearly demonstrates that miR-194 inhibits the acquisition of the EMT
      phenotype in gastric cancer cells by downregulating FoxM1, thereby inhibiting
      cell migration and invasion during cancer progression.

PMID- 24748185
TI  - [Ac-hE-18A-NH2 inhibits the inflammatory response induced by ox-LDL via
      inhibiting NF-kappaB activation in RAW264.7 macrophages].
AB  - OBJECTIVE: To evaluate the effect of Ac-hE-18A-NH2 on TNF-alpha secretion and
      mRNA expression in ox-LDL-stimulated RAW264.7 macrophages and to elucidate the
      possible mechanisms. METHODS: Macrophages were incubated in the medium containing
      various concentrations of Ac-hE18A-NH2 (1-50 MUg/mL) with ox-LDL (50 MUg/mL)
      stimulated. The TNF-alpha level and intracellular cholesterol content were
      measured by commercially available quantitation kits following the manufacturer's
      instructions. TNF-alpha and ATP-binding cassette transporter A1 (ABCA1) mRNA
      expression were detected by real-time PCR. ABCA1 and IkappaB protein -expression
      in the macrophages were determined by Western blot. NF-kappaB activity was
      evaluated by electrophoretic mobility shift assay (EMSA). RESULTS: Ox-LDL
      stimulation induced a significant increase in TNF-alpha secretion, mRNA
      expression, cholesterol accumulation and nuclear factor-kappaB (NF-kappaB)
      activity in RAW264.7 macrophages. Ac-hE-18A-NH2 reduced TNF-alpha secretion and
      mRNA expression, up-regulated the ABCA1 mRNA and protein expression, reduced the
      intracellular cholesterol content, and inhibited NF- kappaB activation in a dose
      dependent manner. Under the same condition and the same concentration, Ac-hE-18A
      NH2 was more efficient than D-4F (apoA-I mimetic peptide) in inhibiting the
      inflammatory response induced by ox-LDL in the macrophages. CONCLUSION: Ac-hE-18A
      NH2 may suppress TNF-alpha secretion and mRNA expression in ox-LDL stimulated
      RAW264.7 macrophages via IkappaB-NF-kappaB signaling pathway. The anti
      inflammatory effect of Ac-hE-18A-NH2 is better than that of apoA-I mimic peptide
      D-4F.

PMID- 24748186
TI  - [Effect of PFT-alpha on apoptosis of spermatogenic cells caused by enorchia].
AB  - OBJECTIVE: To determine the molecular mechanism of germ cell apoptosis via
      investigating the effect of PFT-alpha on the expression of p53 and bcl-2/bax
      during experimental cryptorchid cell apoptosis. METHODS: Male Sprague-Dawley rats
      were assigned into 4 groups: a sham-operated group, a cryptorchid group, a
      cryptorchid+p53 inhibitor (p53 inhibitor-alpha, PFT-alpha) group, and a
      cryptorchid+dissolvent of PFT-alpha [dimethyl sulphoxide (DMSO)] group.
      Unilateral cryptorchidism was surgically induced in the rats of the cryptorchid
      group, PFT-alpha group, and cryptorchid+dissolvent of PFT-alpha group. The rats
      in the PFT-alpha group and cryptorchid+dissolvent of PFT-alpha group were intra
      peritoneally injected PFT-alpha and dissolvent of PFT-alpha, respectively, once a
      day. The rats were killed on the 7th day after the surgery. The morphology of
      spermatogenic epithelium at the side of surgery in the rats was observed under
      light microscope. The apoptosis of spermatogenic cells in the unilateral
      cryptorchidism was evaluated by TUNEL and flow cytometry (FCM). The protein
      expression levels of p53, bcl-2, and Bax were detected by Western blot and
      immunohistochemical assay in turn. RESULTS: Compared with the cryptorchid groups
      and the cryptorchid+dissolvent of PFT-alpha group, the seminiferous epithelium of
      the cryptorchid+p53 inhibitor group appeared orderly, with thicker cell layers
      and lower apoptosis index, weak protein expression level of p53/Bax and strong
      protein expression level of bcl-2. CONCLUSION: PFT-alpha inhibits the germ cell
      apoptosis caused by the experimental cryptorchidism via increasing the expression
      of bcl-2 and decreasing the expression of p53 and bax.

PMID- 24748187
TI  - Meta-analysis of myeloperoxidase gene polymorphism and coronary artery disease
      susceptibility.
AB  - OBJECTIVE: To assess the association between myeloperoxidase (MPO) gene
      polymorphism and coronary artery disease (CAD). METHODS: Several databases were
      used to retrieve relevant literature up to March 2013 by keywords. A Meta
      analysis was performed by Stata12.0 software to estimate the pooled odds ratio
      (OR) and the 95% confidence interval (CI). Heterogeneity among studies was tested
      and sensitivity analysis was applied. Publication bias was examined using Begg's
      funnel plot and Egger's linear regression test. RESULTS: A total of 17 studies
      were included in this Meta-analysis. For MPO -463 G/A polymorphism, the pooled OR
      of A allele vs G allele was 0.58 [95% CI (0.47-0.72)] and the pooled OR of
      genotypes AA+AG vs GG was 0.58 [95% CI (0.46-0.72)]. In subgroup analysis of
      study population, AA and AG genotypes were significantly associated with CAD in
      Asians but not in Europeans. The MPO -463 G/A polymorphism in the stable angina
      pectoris subgroup was evaluated in 3 studies and the pooled OR of A allele vs G
      allele and genotypes AA+AG vs GG for proven CAD was 0.45 [95% CI (0.15-1.37)] and
      0.57 [95% CI (0.19- 1.65)]. For MPO -129 A/G gene polymorphism, the pooled OR of
      genotype GG vs AA+AG was 0.91 [95% CI (0.74-1.10)]. CONCLUSION: A allele of MPO 
      463 G/A gene is associated with decreased risk of CAD except in the Europeans.
      There is no association between MPO -129 A/G gene polymorphisms and CAD risk.

PMID- 24748188
TI  - [Postpartum change of blood pressure and its risk factors in patients with
      hypertensive disorders in pregnancy].
AB  - OBJECTIVE: To investigate the change of blood pressure in patients with
      hypertensive disorders in pregnancy after delivery and the risk factors. METHODS:
      In a retrospective cohort study, we collected subjects from villages and towns in
      Liuyang by cluster sampling method. Before enrolling in this cohort, all had
      established health records from January 2010 to December 2011. We collected the
      medical records and maternal health care manuals of this cohort as our data
      materials, focusing on the blood pressure records as well as related features. We
      compared the differences of recovery rate of postpartum blood pressure in
      different kinds of antenatal blood pressure groups with chi2 test. In order to
      explore the main factors influencing the recovery rate of blood pressure of
      patients with hypertensive disorders in pregnancy, we conducted univariate and
      multivariate analysis by chi2 test and unconditional logistic regression
      analysis. RESULTS: Among the 460 women with hypertensive disorders in pregnancy
      in our analysis, the recovery rate of postpartum blood pressure reached 88.7%.
      Multivariate analysis showed that the risk factors influencing the recovery rate
      of postpartum blood pressure included advanced age (OR=0.436), higher degree of
      hypertensive disorders in pregnancy (OR=0.436), and hypertension with
      simultaneously high systolic and diastolic blood pressures (OR=0.192).
      CONCLUSION: For most patients with hypertensive disorders in pregnancy, the blood
      pressure may decrease to normal level 42 days after delivery. Women with advanced
      age, higher degree of hypertensive disorders in pregnancy and hypertension with
      simultaneously high systolic and diastolic blood pressures should be given more
      attention.

PMID- 24748189
TI  - [Glycyrrhizin inhibits human neutrophil elastase-induced mucin 5AC overproduction
      in human bronchial epithelial cells].
AB  - OBJECTIVE: To investigate the effect of glycyrrhizin (Gly) on human neutrophil
      elastase (HNE)- induced mucin (MUC) 5AC overproduction in human bronchial
      epithelial cells (16HBE), and the potential signaling pathway involved in this
      process. METHODS: The cultured cells were divided into 3 groups: a control group,
      cultured in serum-free DMEM medium; an HNE group, pretreated with HNE alone; and
      a Gly group, incubated with HNE and Gly. After stimulation with a variety of Gly
      concentrations, the cytotoxicity was assessed by methyl thiazolyl tetrazolium
      method. The mRNA expressions of p38, nuclear factor kappaB (NF-kappaB) p65,
      inhibitory kappaBalpha (IkappaBalpha) and MUC5AC were detected by real-time PCR.
      The phosphorylation levels of p38 (p-p38), NF-kappaB p65 (p-NF-kappaB p65) and
      IkappaBalpha (p-IkappaBalpha) were measured by Western blot while the levels of
      MUC5AC protein were analyzed by emzyme-linked immunosorbent assay and
      immunofluorescence. RESULTS: Compared with the control group, the expression
      levels of MUC5AC mRNA and protein in the HNE group were both significantly
      increased. There was a significant increase in p-p38 and p-NF-kappaB p65, while
      the production of IkappaBalpha was much lower than that in the control group. Gly
      significantly inhibited the increase of MUC5AC, p38 and NF-kappaB p65, but
      increased the activity of IkappaBalpha. CONCLUSION: Glycyrrhizin can inhibit
      MUC5AC overproduction via p38-NF-kappaB p65/IkappaBalpha signaling pathway.

PMID- 24748190
TI  - [Therapeutic effect of BMSCs with over-expressed MMP1 on liver fibrosis].
AB  - OBJECTIVE: To investigate the function of bone marrow mesenchymal stem cells
      (BMSCs) with over-expressed matrix metalloproteinase 1 (MMP1) on liver fibrosis.
      METHODS: Fifty SD male rats were randomly divided into 4 groups: recombinant
      adenovirus Adhuman MMP-1(hMMP-1)-enhanced green fluorescent protein (EGFP)
      transfected BMSCs group (Group A, n=10), Ad-EGFP transfected BMSCs group (Group
      B, n=10), liver fibrosis group (Group C, n=15), and a normal group (Group D,
      n=15). The liver fibrosis model was formed by subcutaneous injection of the mixed
      liquor of carbon tetrachloride (CCL4) and vegetable oil. After 10 weeks, the
      model of liver fibrosis was formed. Group A and B were administered the
      transfected BMSCs via the tail veins, while Group C and D were administered
      normal saline. After 3 weeks, the rats were sacrificed. The body weight, liver
      weight, liver function, liver fibrosis indexes and liver pathological changes
      were tested. RESULTS: Compared with the control group, the rats administered
      BMSCs with over-expressed MMP1 showed a significant improvement in the body
      weight, liver weight and plasma albumin (ALB) (P<0.05), and a significant
      reduction in the plasma alanine aminotransferase, total bilirubin, hyaluronic
      acid, laminin and procollagen III (P<0.05). Hematoxylin-eosin staining confirmed
      that the degree of liver fibrosis was significantly ameliorated under average
      visual fields (P<0.05). CONCLUSION: The repair ability of BMSCs on liver fibrosis
      can be enhanced by over-expression of hMMP-1.

PMID- 24748191
TI  - [Helicobacter pylori infection and gastric mucosa change and blood-lipid in
      people undergoing the physical examination in Changsha].
AB  - OBJECTIVE: To explore the relationship between the Helicobacter pylori (H.pylori)
      infection and gastric mucosa change and blood-lipid in people undergoing the
      physical examination in Changsha. METHODS: A total of 2 264 people undergoing
      physical examination were divided into an H. pyloripositive group (n=1 068) and
      an H. pylori-negative group (n=1 196). Gastric mucosa change was diagnosed by
      gastroscopy, blood-lipid and blood sugar were detected, and the statistical
      analysis was performed. RESULTS: The incidence rate of H.pylori infection was
      47.2%. The incidence rate of gastric mucosal erosion, gastric ulcer, duodenal
      ulcer, gastric mucosal atrophy, gastric polyp, dyslipidemia, increase of
      triglyceride were (TG) and decrease of the high density lipoprotein cholesterol
      (HDL-C) in the H.pylori-positive group were all higher than those in the H.pylori
      negative group (P<0.01 or P<0.05). In the H. pylori-positive group, the level of
      TG in people with gastric mucosal erosion, gastric ulcer and duodenal ulcer was
      higher than that in people with normal gastric mucosa or mild gastritis, and HDL
      C was lower than that in people with normal gastric mucosa or mild gastritis.
      CONCLUSION: H. pylori infection can induce the gastric mucosa injury and
      dyslipidemia, which may result in the occurrence and development of coronary
      heart disease by increasing TG and decreasing HDL-C, thus increasing the risk of
      atherosclerosis.

PMID- 24748192
TI  - [Expression of serum GDF15 and its clinical significance in multiple myeloma
      patients].
AB  - OBJECTIVE: To determine the serum level of the growth differentiation factor 15
      (GDF15) in multiple myeloma (MM) patients and analyze its level with other
      clinical parameters, and to investigate its significance in the formation,
      development and prognosis assessment of MM. METHODS: We used enzyme-linked
      immunosorbent assay (ELISA) to measure the serum level of GDF15 in an MM group
      (24 pre-treatment patients) and in 20 healthy controls. All patients' clinical
      data were collected. RESULTS: The serum GDF15 level was significantly higher in
      the MM group [(1.37+/-0.64) ng/mL] than in the normal control group [(0.14+/
      0.06) ng/mL, P<0.01]. The mean serum GDF15 level in the MM patients in ISS stage
      III was (1.57+/-0.48) ng/mL, significantly higher than that of ISS stage (I+II)
      [(0.77+/-0.34) ng/mL, P<0.05]. There was no significant positive correlation
      between the serum GDF15 level and serum monoclonal proteins (M protein) level,
      beta2-microglobulin and creatinemia (P<0.05), but significant inverse correlation
      was found between the GDF15 level with hemoglobin concentration and platelet
      count respectively (P<0.05). Serum GDF15 level was not associated with patients'
      age, albumin, lactic dehydrogenase (LDH), C-reactive protein (CRP), calcemia or
      leukocyte count (P>0.05). After 3 cycles of chemotherapy, patients with a>50%
      reduction of M protein had a significant reduction of GDF15, while for the
      patients whose M protein did not decrease obviously, their corresponding serum
      GDF15 level increased. CONCLUSION: The serum GDF15 level may reflect the tumor
      burden in the MM patients, which increases obviously, is related with ISS,
      positively correlated with serum M protein level, beta2- microglobulin level,
      serum creatinine and negatively with hemoglobin concentration and platelet count.
      The change of serum GDF15 level has some relation with the extent of M protein
      reduction, suggesting it may be used as a marker for therapy response.

PMID- 24748193
TI  - [Effect of alendronate-loaded bone cement on osteoblast].
AB  - OBJECTIVE: To determine the effect of bone cement, with different amounts of
      alendronate on osteoblast, and determine the cytotoxicity of alendronate
      integrated bone cement from the viewpoint of cell biology. METHODS: According to
      different additions (0, 10, 50, 100, 500, 1 000 mg) of alendronate in 50 g
      Cemex(r)XL bone cement powder, the experiments were divided into 6 groups, namely
      G0-G5 groups. In all groups, the adhesive capacity of osteoblast-like cells MG-63
      was evaluated by electron microscope, the optical density (OD) value of cells by
      MTT colorimetry method, the alkaline phosphatase activity (AKP) by AKP assay kit,
      the apoptosis rates by Annexin-V-FITC apoptosis detection kit, and the bone
      mineralization potentiality by phase contrast microscope. RESULTS: The adhesive
      capacity of MG-63 was good in all groups. Compared with the G0 group, the cell
      apoptosis was inhibited in G1-G4 groups while in G5 group the cell apoptosis was
      promoted and cell proliferation was inhibited (P<0.05). In all groups, no
      significant difference was found in alkaline phosphatase activity and bone
      mineralization potentiality (P>0.05). CONCLUSION: Less than 500 mg alendronate
      added in Cemex(r)XL 50 g bone cement powder has no cytotoxicity on osteoblasts.

PMID- 24748194
TI  - [Foot tapping test for lower extremity motor function of cervical spondylotic
      myelopathy].
AB  - OBJECTIVE: To investigate the standard value of foot tapping test (FTT) in
      healthy population and FTT for lower extremity motor function in patients with
      cervical compressive myelopathy. METHODS: Totally 124 patients [68 males,
      (58.49+/-14.60) years old; 56 females, (57.55+/-18.27) years old] diagnosed of
      cervical myelopathy and 160 healthy volunteers [80 males, (45.43+/-17.98) years
      old; 80 females, (45.2+/-17.47) years old] participated in our study. The
      patients who underwent surgery were evaluated both before and 1 year after the
      surgery. We performed FTT and Grip and Release Test and evaluated with the
      modified Japanese Orthopaedic Association (JOA) score for cervical myelopathy.
      RESULTS: The value of FTT was (22.23+/-2.53) in myelopathic patients,
      significantly lower than (33.23 +/-3.17) in the healthy group (decreasing with
      age) (P<0.05). The value of FTT was positively correlated with the lower
      extremity motor function of modified JOA score and the value of Grip and Release
      Test. In the patients who underwent surgery, the value of FTT was (22.23+/-2.53)
      preoperatively and was improved to (28.48+/-1.99) at one year postoperatively
      (P<0.05). CONCLUSION: The FTT score has been improved by surgery. The FTT is an
      easy and useful quantitative assessment for lower extremity motor function in
      patients with cervical myelopathy, especially those who cannot walk.

PMID- 24748195
TI  - [Epidemiological investigation of pelvic fracture in 9 third-tier hospitals in 5
      cities in Hunan].
AB  - OBJECTIVE: To analyze the epidemiological characteristics and treatment situation
      of pelvic fractures in 5 cities in Hunan, improve the treatment and provide
      epidemiological data for policymakers. METHODS: The clinical data of 65 patients
      with pelvic fractures were collected from 9 third-tier hospitals in Hunan from
      October 2012 to March 2013. The gender, age, cause, volume of blood transfusion,
      and prognosis were analyzed with SPSS 13.0. RESULTS: There were 44 male and 21
      female patients (2.10:1.00). The age ranged from11 to 86 years and 74.6% of the
      patients were between 20 and 59. The main cause was traffic injury (30 cases,
      46.2%) and fall injury (22 cases, 33.8%). About 73.8% patients suffered
      associated injuries all over the body. By Tile's classification of pelvic
      fractures, the average blood transfusion of type A was 483.33 mL, that of type B
      was 1 026.92 mL and type C was 1 905.56 mL. Compared with type A, the treatment
      outcome of type C patients was worse. CONCLUSION: Pelvic fractures are mostly
      caused in young and middle-aged males by high-energy. Tile C pelvic fractures
      need more blood transfusion and have poor prognosis. Patients had better be taken
      straight to municipal hospitals by expertise. Safety education for high-risk
      groups should be enhanced to reduce the incidence of pelvic fractures.

PMID- 24748196
TI  - [Early recognition of deteriorating patient program in department of cardiac
      surgery].
AB  - OBJECTIVE: To explore the application and the effect of early recognition of
      deteriorating patient program in department of cardiac surgery. METHODS: We used
      the early recognition of deteriorating patient program in the cardiac surgery
      groups, including cardiac surgeons, nurses in ward, ICU and operation rooms of
      the cardiac surgery department, and compared the satisfaction of nurses and
      doctors, handover time, handover score of critical patients, and rate of
      unplanned ICU admission before and after the intervention. RESULTS: After using
      the early recognition of deteriorating patient program, the satisfaction of
      doctors and nurses was increased, the handover time was lowered 0.56 min/time
      (t=2.22, P<0.05), the handover score of critical patients enhanced by 19.59
      points (t=30.57, P<0.001), the rate of unplanned ICU readmission after the
      operation reduced by 4.8% (chi2=4.14, P<0.05). CONCLUSION: Early recognition of
      deteriorating patient program can improve the safety of cardiac patients, enhance
      the self-confidence of nurses and work efficiency.

PMID- 24748197
TI  - [Nucleic acid aptamers in diagnosis of diseases].
AB  - Aptamers are single-stranded oligonucleotide ligands selected from a random pool
      of oligonucleotide sequences by systematic evolution of ligands by exponential
      enrichment. With the advantages of binding to targets with high specificity and
      affinity, aptamers have been used in the diagnosis widely, such as biochemistry
      detection, discovery of new tumor markers, molecular imaging, pathogenic and
      microorganism detection, showing a good application prospect. 

PMID- 24748198
TI  - [Changes of blood pressure and S-100B, neuron specific enolase protein in
      hypertensive dogs after renal sympathetic denervation].
AB  - OBJECTIVE: To observe the changes of blood pressure and S-100B, neuron specific
      enolase (NSE) protein in hypertensive dogs with high fat diet after catheter
      based renal sympathetic denervation. METHODS: Twelve Beagles were divided into an
      interventional group (n=6) and a sham-operation group (n=6). After baseline
      measurements, the Beagles were fed with lard oil for 3 months. After 3 months,
      the interventional group had renal sympathetic denervation by percutaneous
      catheter based radiofrequency ablation and the control group had renal
      angiography. The blood pressure, plasma S-100B, and NSE before the operation and
      3 days, 1 week, 2 weeks, 1 month, 2 months and 3 months after the operation were
      measured. RESULTS: The dogs had significantly higher levels of systolic blood
      pressure (SBP), diastolic blood pressure (DBP) and mean arterial pressure (MBP)
      compared to its baselines (P<0.05). The SBP, DBP and MBP in the interventional
      group were significantly lower than those in the control group 1 month and 3
      months after the operation (P<0.05). Three months after the operation, renal
      angiography in all dogs revealed no sign of renal artery stenosis. Plasma S-100B
      and NSE expression in the interventional group were higher than those in the
      control group 3 days, 1 week and 2 weeks after the operation (P<0.05).
      CONCLUSION: Renal sympathetic denervation can significantly reduce the SBP, DBP
      and MBP in hypertensive dogs. The plasma S-100B and NSE may be used as indicators
      for assessment of renal nerve injury after renal sympathetic denervation.

PMID- 24748199
TI  - [Methodology of BMSCs in repairing ureteral injury in mice via renal artery
      transplantation].
AB  - OBJECTIVE: To investigate the effect of bone marrow mesenchymal stem cells
      (BMSCs) on ureteral injury repair via renal artery transplantation. METHODS: The
      left ureteral obstruction model was set up in 49 Balb/c mice by micro vascular
      clamp. The microscopic vascular clamp was taken out to lift the left ureteral
      obstruction after 10 days. The mice were randomly divided into an experimental
      group (n=25) and a control group (n=24). Balb/c mice BMSCs transfected by
      luciferase (Luc) were transplanted immediately through the renal artery after
      removing the microscopic vascular clamp from the experimental group; while mice
      in the control group was closed the incision after the microscopic vascular clamp
      was removed immediately and without BMSCs transplant. Magnetic resonance imaging
      (MRI) was used to scan the experimental mice. By measuring the left renal pelvis
      volume of the experimental mice at different time points and comparing the left
      ureter recanalization rate after removing left ureteral obstruction of the
      experimental group and the control group, we evaluated the repair effect of BMSCs
      on ureteral injury. RESULTS: The volume of the left renal pelvis in experimental
      mice became bigger obviously after the left ureter was obstructed (P<0.01). The
      left renal pelvis volume of the experimental group and the control group had no
      statistical significance 10 days after the left ureteral obstruction was set up
      (P=0.693). In the experimental group, the left ureter recanalization rate was
      higher than that in the control group, after removing the left ureteral
      obstruction (P=0.012). CONCLUSION: Transplantation through the renal artery can
      promote the restoration of ureteral injury in mice.

PMID- 24748200
TI  - [Effect of nutrition and food safety education among middle school students in a
      poverty-stricken county in west China].
AB  - OBJECTIVE: To evaluate the effect of nutrition and food safety education among
      middle school students in a poverty-stricken county in west China, and to explore
      the better education model for further education. METHODS: Students of grade 7 to
      9 were selected from 4 middle schools in the country through multi-stage cluster
      sampling for the questionnaire, and the schools were assigned into an
      intervention group or a control group. After students in the intervention schools
      completed one year nutrition and food safety education with the textbooks,
      students were chosen from the same 4 schools to finish the same questionnaire
      again. RESULTS: A total of 410 students from grade 7 to 9 were selected at the
      baseline study, and 474 students in the final study. The essential
      characteristics of the 2 groups were not statistically significant (P>0.05). In
      the baseline investigation, the differences in the scores on nutrition and food
      safety knowledge, attitude and practice between the 2 groups were not significant
      (P>0.05). In the final study, the scores on the knowledge, attitude of nutrition
      knowledge learning, and dietary habits among students in the intervention group
      were significantly higher than those in the control group (P<0.05). School
      students mixed model demonstrated that the intervention was protective factor on
      scores of knowledge, in particular with nutrition related diseases and reasonable
      diet (P<0.05). But the intervention didn't affect the scores on attitude in both
      ways (P>0.05). CONCLUSION: Nutrition and food safety education can improve the
      nutrition and food safety knowledge effectively. The curriculum should be further
      standardized and different emphases should be set up to different grades to
      cultivate healthy diet behaviors.

PMID- 24748201
TI  - Diagnostic testing of pediatric fevers: meta-analysis of 13 national surveys
      assessing influences of malaria endemicity and source of care on test uptake for
      febrile children under five years.
AB  - BACKGROUND: In 2010, the World Health Organization revised guidelines to
      recommend diagnosis of all suspected malaria cases prior to treatment. There has
      been no systematic assessment of malaria test uptake for pediatric fevers at the
      population level as countries start implementing guidelines. We examined test use
      for pediatric fevers in relation to malaria endemicity and treatment-seeking
      behavior in multiple sub-Saharan African countries in initial years of
      implementation. METHODS AND FINDINGS: We compiled data from national population
      based surveys reporting fever prevalence, care-seeking and diagnostic use for
      children under five years in 13 sub-Saharan African countries in 2009-2011/12 (n
      = 105,791). Mixed-effects logistic regression models quantified the influence of
      source of care and malaria endemicity on test use after adjusting for
      socioeconomic covariates. Results were stratified by malaria endemicity
      categories: low (PfPR2-10<5%), moderate (PfPR2-10 5-40%), high (PfPR2-10>40%).
      Among febrile under-fives surveyed, 16.9% (95% CI: 11.8%-21.9%) were tested.
      Compared to hospitals, febrile children attending non-hospital sources (OR: 0.62,
      95% CI: 0.56-0.69) and community health workers (OR: 0.31, 95% CI: 0.23-0.43)
      were less often tested. Febrile children in high-risk areas had reduced odds of
      testing compared to low-risk settings (OR: 0.51, 95% CI: 0.42-0.62). Febrile
      children in least poor households were more often tested than in poorest (OR:
      1.63, 95% CI: 1.39-1.91), as were children with better-educated mothers compared
      to least educated (OR: 1.33, 95% CI: 1.16-1.54). CONCLUSIONS: Diagnostic testing
      of pediatric fevers was low and inequitable at the outset of new guidelines.
      Greater testing is needed at lower or less formal sources where pediatric fevers
      are commonly managed, particularly to reach the poorest. Lower test uptake in
      high-risk settings merits further investigation given potential implications for
      diagnostic scale-up in these areas. Findings could inform continued
      implementation of new guidelines to improve access to and equity in point-of-care
      diagnostics use for pediatric fevers.

PMID- 24748202
TI  - The effects of propionate and valerate on insulin responsiveness for glucose
      uptake in 3T3-L1 adipocytes and C2C12 myotubes via G protein-coupled receptor 41.
AB  - Since insulin resistance can lead to hyperglycemia, improving glucose uptake into
      target tissues is critical for regulating blood glucose levels. Among the free
      fatty acid receptor (FFAR) family of G protein-coupled receptors, GPR41 is known
      to be the Galphai/o-coupled receptor for short-chain fatty acids (SCFAs) such as
      propionic acid (C3) and valeric acid (C5). This study aimed to investigate the
      role of GPR41 in modulating basal and insulin-stimulated glucose uptake in
      insulin-sensitive cells including adipocytes and skeletal muscle cells.
      Expression of GPR41 mRNA and protein was increased with maximal expression at
      differentiation day 8 for 3T3-L1 adipocytes and day 6 for C2C12 myotubes. GPR41
      protein was also expressed in adipose tissues and skeletal muscle. After
      analyzing dose-response relationship, 300 uM propionic acid or 500 uM valeric
      acid for 30 min incubation was used for the measurement of glucose uptake. Both
      propionic acid and valeric acid increased insulin-stimulated glucose uptake in
      3T3-L1 adipocyte, which did not occur in cells transfected with siRNA for GPR41
      (siGPR41). In C2C12 myotubes, these SCFAs increased basal glucose uptake, but did
      not potentiate insulin-stimulated glucose uptake, and siGPR41 treatment reduced
      valerate-stimulated basal glucose uptake. Therefore, these findings indicate that
      GPR41 plays a role in insulin responsiveness enhanced by both propionic and
      valeric acids on glucose uptake in 3T3-L1 adipocytes and C2C12 myotubes, and in
      valerate-induced increase in basal glucose uptake in C2C12 myotubes. 

PMID- 24748203
TI  - Potassium enrichment stimulates the growth and reproduction of a clone of Daphnia
      dentifera.
AB  - Nutrient limitation commonly constrains organisms in natural ecosystems.
      Typically, ecologists focus on limitation by N and P. However, other nutrients
      can limit growth or reproduction. Here we focus on K limitation of invertebrate
      consumers (Daphnia dentifera) and phytoplankton in freshwater lakes. All
      organisms require K for several metabolic processes. In freshwater, K could limit
      growth because low external concentrations can increase the energetic costs of
      accumulating K. Furthermore, in a study linking K to disease, we previously found
      that K enrichment of water from one low-K lake stimulated the growth and
      reproduction of Daphnia. Here we test whether K could limit the production of
      Daphnia and phytoplankton across lakes and years. We repeated a life table
      experiment using water collected from a low-K lake during a different year. K
      again stimulated Daphnia reproduction. We also enriched water from 12 lakes with
      K or P and measured short-term growth of Daphnia and the resident algal
      community. Both nutrients increased Daphnia growth in five lakes. However, only P
      enhanced algal production. P stimulation of Daphnia positively correlated with
      algal quantity and the ratio of C to P in seston. However, K stimulation of
      Daphnia was not correlated with these factors or the background concentration of
      K. Thus, this study shows repeatable K-limited animal physiology in nature.
      Further, we can exclude the hypothesis that K stimulates Daphnia indirectly by
      enhancing algal production. These patterns call for future physiological studies
      to uncover the mechanistic basis of K limitation in natural systems. 

PMID- 24748204
TI  - Grazer removal and nutrient enrichment as recovery enhancers for overexploited
      rocky subtidal habitats.
AB  - Increasing anthropogenic pressures are causing long-lasting regime shifts from
      high-diversity ecosystems to low-diversity degraded ones. Understanding the
      effects of multiple threats on ecosystems, and identifying processes allowing for
      the recovery of biodiversity, are the current major challenges in ecology. In
      several temperate marine areas, large parts of rocky subtidal habitats
      characterised by high diversity have been completely degraded to barren grounds
      by overfishing, including illegal date mussel fishing. Bare areas are
      characterized by the dominance of sea urchins whose grazing perpetuates the
      impact of overfishing. We investigated experimentally the separate and combined
      effects of nutrient enrichment and sea urchin exclusion on the recovery of barren
      grounds. Our results indicate that the two factors have a synergistic effect
      leading to the re-establishment of erect macroalgal canopies, enhancing the
      structural complexity of subtidal assemblages. In particular, in the overfished
      system considered here, the recovery of disturbed assemblages could occur only if
      sea urchins are removed. However, the recolonization of barren grounds by erect
      macroalgae is further enhanced under enriched conditions. This study demonstrates
      that the recovery of dramatically depleted marine habitats is possible, and
      provides useful indications for specific management actions, which at present are
      totally lacking, to achieve the restoration of barren grounds caused by human
      activity. 

PMID- 24748205
TI  - Demographic characteristics of Ghanaian optometry students and factors
      influencing their career choice and institution of learning.
AB  - Optometry is only provided at tertiary level in two institutions in Ghana, with
      an average of 50 students graduating each year for a population of approximately
      24.6 million. No information on the demography of optometry students and factors
      that influence their choice of optometry as a career and institution of learning
      is available. This information is important as it will assist optometry
      institutions to formulate effective student recruitment strategies. To assess the
      demographic characteristics of Ghanaian optometry students, the factors that
      influence their selection of optometry as a career and institution of learning.
      We conducted a cross sectional study among Ghanaian optometry students using a
      structured questionnaire to collect data on the demographic characteristics and
      factors that might influence their choice of optometry as a career as well as
      choice of institution of learning. Two hundred and eighty students from the two
      optometry training institutions in Ghana; University of Cape Coast (48.2%) and
      Kwame Nkrumah University of Science and Technology (51.8%) responded to the
      questionnaire. Their ages ranged from 17 to 28 years with most being males
      (72.5%), and the majority (79%) being from urban areas. The main factors that
      influenced their career choice were job availability after graduation (90%) and
      desire to help other people (89.2%). Factors that influenced their institution
      choice were preference for an institution (36.8%) and proximity to home (24.4%).
      In the absence of adequate optometry jobs in the public health sector, women will
      remain marginalised specifically those in rural areas. This marginalisation is
      however, a reflection of a broader societal disadvantage for women. Greater
      effort needs to be made to recruit high school students from rural areas to study
      optometry and more institutions need to provide optometry instruction throughout
      the country.

PMID- 24748206
TI  - Increased expression of HSP27 inhibits invasion and metastasis in human
      esophageal squamous cell carcinoma.
AB  - Previous studies have indicated that heat shock protein 27 (HSP27) had high
      correlation with the development and progression in several tumors. However, the
      roles of HSP27 in esophageal squamous cell carcinoma (ESCC) were uncertain. The
      aim in this study is to investigate the potential roles of HSP27 in the
      metastasis of ESCC. The expression of HSP27 in ESCC tissues and four human
      esophageal cancer cell lines were examined by immunohistochemistry and Western
      blotting, respectively. Wound healing assays, transwell assays, and in vivo
      assays were used to identify the differences of metastasis potential between
      normal and HSP27 overexpressed cells. HSP27 expression was downregulated in
      cancer tissue compared to the matched normal tissue. And the positive staining
      was mainly located in the cytoplasm. Statistical analyses showed that the
      expression of HSP27 in ESCC was significantly correlated with the tumor
      differentiation (P = 0.023), the patient's TNM stage (P = 0.013), lymph
      metastasis (P = 0.020), and distant metastasis (P = 0.017). HSP27 expression was
      significantly lower in highly metastatic cells than the less ones. The metastatic
      potentials of EC9706-H and EC109-H cells were higher than EC9706-L and EC109-L
      cells. In vitro and in vivo assays showed that overexpression of HSP27 in highly
      metastatic cells dramatically decreased their metastatic capacity. This study
      indicated that the expression level of HSP27 may be inversely correlated with the
      metastasis behavior of ESCC, and HSP27 may play an important role in this
      progression. HSP27 may be a potential molecular target for the therapy and
      prognosis of patients with ESCC.

PMID- 24748207
TI  - Capturing large shape variations of liver using population-based statistical
      shape models.
AB  - PURPOSE: Statistical shape models (SSMs) represent morphological variations of a
      specific object. When there are large shape variations, the shape parameters
      constitute a large space that may include incorrect parameters. The human liver
      is a non-rigid organ subject to large deformations due to external forces or body
      position changes during scanning procedures. We developed and tested a population
      based model to represent the shape of liver. METHODS: Upper abdominal CT-scan
      input images are represented by a conventional shape model. The shape parameters
      of individual livers extracted from the CT scans are employed to classify them
      into different populations. Corresponding to each population, an SSM model is
      built. The liver surface parameter space is divided into several subspaces which
      are more compact than the original space. The proposed model was tested using 29
      CT-scan liver image data sets. The method was evaluated by model compactness,
      reconstruction error, generality and specificity measures. RESULTS: The proposed
      model is implemented and tested using CT scans that included liver shapes with
      large shape variations. The method was compared with conventional and recently
      developed shape modeling methods. The accuracy of the proposed model was nearly
      twice that achieved with the conventional model. The proposed population-based
      model was more general compared with the conventional model. The mean
      reconstruction error of the proposed model was 0.029 mm while that of the
      conventional model was 0.052 mm. CONCLUSION: A population-based model to
      represent the shape of liver was developed and tested with favorable results.
      Using this approach, the liver shapes from CT scans were modeled by a more
      compact, more general, and more accurate model.

PMID- 24748208
TI  - Variable dose interplay effects across radiosurgical apparatus in treating
      multiple brain metastases.
AB  - PURPOSE: Normal brain tissue doses have been shown to be strongly apparatus
      dependent for multi-target stereotactic radiosurgery. In this study, we
      investigated whether inter-target dose interplay effects across contemporary
      radiosurgical treatment platforms are responsible for such an observation.
      METHODS: For the study, subsets ([Formula: see text] and 12) of a total of 12
      targets were planned at six institutions. Treatment platforms included the (1)
      Gamma Knife Perfexion (PFX), (2) CyberKnife, (3) Novalis linear accelerator
      equipped with a 3.0-mm multi-leaf collimator (MLC), and the (4) Varian Truebeam
      flattening-filter-free (FFF) linear accelerator also equipped with a 2.5 mm MLC.
      Identical dose-volume constraints for the targets and critical structures were
      applied for each apparatus. All treatment plans were developed at individual
      centers, and the results were centrally analyzed. RESULTS: We found that dose
      volume constraints were satisfied by each apparatus with some differences noted
      in certain structures such as the lens. The peripheral normal brain tissue doses
      were lowest for the PFX and highest for TrueBeam FFF and CyberKnife treatment
      plans. Comparing the volumes of normal brain receiving 12 Gy, TrueBeam FFF,
      Novalis, and CyberKnife were 180-290% higher than PFX. The mean volume of normal
      brain-per target receiving 4-Gy increased by approximately 3.0 cc per target for
      TrueBeam, 2.7 cc per target for CyberKnife, 2.0 cc per target for Novalis, and
      0.82 cc per target for PFX. The beam-on time was shortest with the TrueBeam FFF
      (e.g., 6-9 min at a machine output rate of 1,200 MU/min) and longest for the PFX
      (e.g., 50-150 mins at a machine output rate of 350 cGy/min). CONCLUSION: The
      volumes of normal brain receiving 4 and 12 Gy were higher, and increased more
      swiftly per target, for Linac-based SRS platforms than for PFX. Treatment times
      were shortest with TrueBeam FFF.

PMID- 24748209
TI  - Wavelet denoising for quantum noise removal in chest digital tomosynthesis.
AB  - PURPOSE: Quantum noise impairs image quality in chest digital tomosynthesis (DT).
      A wavelet denoising processing algorithm for selectively removing quantum noise
      was developed and tested. METHODS: A wavelet denoising technique was implemented
      on a DT system and experimentally evaluated using chest phantom measurements
      including spatial resolution. Comparison was made with an existing post
      reconstruction wavelet denoising processing algorithm reported by Badea et al.
      (Comput Med Imaging Graph 22:309-315, 1998). The potential DT quantum noise
      decrease was evaluated using different exposures with our technique (pre
      reconstruction and post-reconstruction wavelet denoising processing via the
      balance sparsity-norm method) and the existing wavelet denoising processing
      algorithm. Wavelet denoising processing algorithms such as the contrast-to-noise
      ratio (CNR), root mean square error (RMSE) were compared with and without wavelet
      denoising processing. Modulation transfer functions (MTF) were evaluated for the
      in-focus plane. We performed a statistical analysis (multi-way analysis of
      variance) using the CNR and RMSE values. RESULTS: Our wavelet denoising
      processing algorithm significantly decreased the quantum noise and improved the
      contrast resolution in the reconstructed images (CNR and RMSE: pre-balance
      sparsity-norm wavelet denoising processing versus existing wavelet denoising
      processing, P<0.05; post-balance sparsity-norm wavelet denoising processing
      versus existing wavelet denoising processing, P<0.05; CNR: with versus without
      wavelet denoising processing, P<0.05). The results showed that although MTF did
      not vary (thus preserving spatial resolution), the existing wavelet denoising
      processing algorithm caused MTF deterioration. CONCLUSIONS: A balance sparsity
      norm wavelet denoising processing algorithm for removing quantum noise in DT was
      demonstrated to be effective for certain classes of structures with high
      frequency component features. This denoising approach may be useful for a variety
      of clinical applications for chest digital tomosynthesis when quantum noise is
      present.

PMID- 24748211
TI  - The clinical impact of subspecialized radiologist reinterpretation of abdominal
      imaging studies, with analysis of the types and relative frequency of
      interpretation discrepancies.
AB  - PURPOSE: The primary objective of this study was to determine the clinical impact
      and value of abdominal imaging reinterpretations by subspecialized abdominal
      imagers. METHODS: Secondary interpretations for computed tomography (CT),
      magnetic resonance (MR), and ultrasound (US) abdominal studies performed outside
      our institution over a 7-month period were retrospectively compared to the
      primary (outside) interpretation, with interpretive differences recorded.
      Clinical notes, pathology and subsequent imaging determined ground truth
      diagnosis and the clinical impact of any interpretive discrepancies were graded
      as having high, medium, or little/no clinical impact. Interpretive comparisons
      were scored into categories: (1) no difference; (2) incidental findings of no
      clinical impact; (3) finding not reported; (4) significance of finding
      undercalled; (5) significance of finding overcalled; (6) finding misinterpreted;
      and (7) multiple discrepancy types in one report. RESULTS: 398 report comparisons
      were reviewed on 380 patients. There were 300 CT, 60 MR, and 38 US examinations.
      The primary report had 5.0% (20/398) high clinical impact interpretive
      discrepancies and 7.5% (30/398) medium clinical impact discrepancies. The
      subspecialized secondary report had no high clinical impact discrepancies and
      8/398 (2.0%) medium clinical impact discrepancies. In order of frequency, high
      and medium impact discrepancies in the primary report consisted of 50% overcalls,
      26% unreported findings, 18% undercalls, 4% misinterpretations, and 2% multiple
      discrepancies. CONCLUSIONS: Subspecialty review of abdominal imaging exams can
      provide clinical benefit. Half of the discrepancies in this series of abdominal
      reinterpretations were due to overcalls.

PMID- 24748210
TI  - Multi-trajectories automatic planner for StereoElectroEncephaloGraphy (SEEG).
AB  - PURPOSE: StereoElectroEncephaloGraphy (SEEG) is done to identify the
      epileptogenic zone of the brain using several multi-lead electrodes whose
      positions in the brain are pre-operatively defined. Intracranial hemorrhages due
      to disruption of blood vessels can cause major complications of this procedure
      ([Formula: see text]1%). In order to increase the intervention safety, we
      developed and tested planning tools to assist neurosurgeons in choosing the best
      trajectory configuration. METHODS: An automated planning method was developed
      that maximizes the distance of the electrode from the vessels and avoids the
      sulci as entry points. The angle of the guiding screws is optimized to reduce
      positioning error. The planner was quantitatively and qualitatively compared with
      manually computed trajectories on 26 electrodes planned for three patients
      undergoing SEEG by four neurosurgeons. Quantitative comparison was performed
      computing for each trajectory using (a) the Euclidean distance from the closest
      vessel and (b) the incidence angle. RESULTS: Quantitative evaluation shows that
      automatic planned trajectories are safer in terms of distance from the closest
      vessel with respect to manually planned trajectories. Qualitative evaluation
      performed by four neurosurgeons showed that the automatically computed
      trajectories would have been preferred to manually computed ones in 30% of the
      cases and were judged good or acceptable in about 86% of the cases. A significant
      reduction in time required for planning was observed with the automated system
      (approximately 1/10). CONCLUSION: The automatic SEEG electrode planner satisfied
      the essential clinical requirements, by providing safe trajectories in an
      efficient timeframe.

PMID- 24748212
TI  - Preconception health promotion among Maryland women.
AB  - Despite current guidelines that all reproductive age women receive preconception
      care (PCC), most US women do not, especially women with a prior birth. The
      objective of our study was to identify factors associated with receipt of PCC
      health promotion counseling among Maryland women and to assess whether prior
      birth outcome affects receipt of counseling. We analyzed Maryland pregnancy risk
      assessment monitoring system data for a stratified random sample of women with a
      live birth in 2009-2010; 3,043 women with PCC data were included in the analysis.
      The dependent variable was receipt of any PCC counseling, and the primary
      independent variable, prior pregnancy outcome (no prior live birth, term,
      preterm). 33.1 % of the weighted sample received PCC. Odds of PCC were similar
      for women with a history of prior prior preterm birth (aOR 1.00, 95 % CI 0.57
      1.78) and no prior live birth, but decreased for women with a prior full term
      delivery (aOR 0.69, 95 % CI 0.51-0.94). They were decreased for women with
      unintended births (aOR 0.36, 95 % CI 0.26-0.51) and increased for women with a
      diagnosis of asthma (aOR 1.74, 95 % CI 1.05-2.89) or diabetes (aOR 2.79, 95 % CI
      1.20-6.45), who used multivitamins (aOR 2.58, 95 % CI 1.92-3.47), and had dental
      cleanings (aOR 1.60, 95 % CI 1.16-2.18). Although selected preventive health
      behaviors and high-risk conditions were associated with PCC, most women did not
      receive PCC. Characterization of women who do not receive PCC health promotion
      counseling in Maryland may assist in efforts to enhance service delivery.

PMID- 24748213
TI  - Nutrition advice during pregnancy: do women receive it and can health
      professionals provide it?
AB  - A healthy diet during pregnancy is essential for normal growth and development of
      the foetus. Pregnant women may obtain nutrition information from a number of
      sources but evidence regarding the adequacy and extent of this information is
      sparse. A systematic literature review was conducted to identify sources of
      nutrition information accessed by pregnant women, their perceived needs for
      nutrition education, the perceptions of healthcare providers about nutrition
      education in pregnancy, and to assess the effectiveness of public health programs
      that aim to improve nutritional practices. The Scopus data base was searched
      during January, 2013 and in February 2014 to access both qualitative and
      quantitative studies published between 2002 and 2014 which focused on healthy
      pregnant women and their healthcare providers in developed countries. Articles
      were excluded if they focused on the needs of women with medical conditions,
      including obesity, gestational diabetes or malnutrition. Of 506 articles
      identified by the search terms, 25 articles were deemed to be eligible for
      inclusion. Generally, women were not receiving adequate nutrition education
      during pregnancy. Although healthcare practitioners perceived nutrition education
      to be important, barriers to providing education to clients included lack of
      time, lack of resources and lack of relevant training. Further well designed
      studies are needed to identify the most effective nutrition education strategies
      to improve nutrition knowledge and dietary behaviours for women during antenatal
      care.

PMID- 24748214
TI  - Breastfeeding practices in relation to country of origin among women living in
      Denmark: a population-based study.
AB  - The objective of this study was to describe breastfeeding practices and to
      compare the risk of suboptimal breastfeeding of women living in Denmark according
      to country of origin, and further to examine how socio-economic position and
      duration of stay in the country affected this risk. Information on breastfeeding
      of 42,420 infants born 2002-2009 and living in eighteen selected Danish
      municipalities was collected from the Danish Health Visitor's Child Health
      Database. The data was linked with data on maternal socio-demographic information
      from Danish population-covering registries. Suboptimal breastfeeding was defined
      as <4 months of full breastfeeding as described by the Danish Health and
      Medicines Authority. We used logistic regression to model the crude associations
      between suboptimal breastfeeding and country of origin, and taking maternal age
      and parity, and a variety of parental socio-economic measures into account.
      Suboptimal breastfeeding was more frequent among non-Western migrant women than
      among women of Danish origin. Women who were descendants of Turkish and Pakistani
      immigrants had a higher risk of suboptimal breastfeeding as compared to the group
      of women who had migrated from the same countries, suggesting that acculturation
      did not favor breastfeeding. For all but the group of women who had migrated from
      Pakistan, adjustment for socio-demographic indicators (age, parity, education,
      attachment to labour market, and income) eliminated the increased risk of
      suboptimal breastfeeding. There was no evidence for differences in the
      breastfeeding support provided at hospital level according to migrant status.
      Suboptimal breastfeeding was more frequent among women who were non-Nordic
      migrants and descendants of migrants than among women with Danish origin.

PMID- 24748215
TI  - Racial and ethnic disparities in educational achievement and aspirations:
      findings from a statewide survey from 1998 to 2010.
AB  - Educational achievement and attainment are associated with health outcomes across
      the entire life span. The objective of this study was to determine whether
      racial/ethnic disparities in academic achievement and educational aspirations
      have changed over time. The study used data from the Minnesota Student Survey
      (MSS) from 1998, 2001, 2004, 2007, and 2010. The MSS is administered to
      adolescents in public secondary schools, charter schools, and tribal schools.
      Measures of academic achievement and educational aspirations were examined by
      race/ethnicity, poverty status, and family structure. Chi square tests evaluated
      differences in the above proportions. The analytic sample included 351,510
      adolescents (1998, N = 67,239; 2001, N = 69,177; 2004, N = 71,084; 2007, N =
      72,312; and 2010, N = 71,698). Study participants ranged in age from 13 to 19
      years (mean = 15.9, SD = 1.6). Most were white (81.7 %), followed by 5.4 % Asian
      American/Pacific Islander, 4.3 % Black/African American, 2.7 % Hispanic/Latino, 1
      % American Indian, and 4.9 % mixed race. Results showed that academic achievement
      fluctuated amongst all the racial/ethnic groups, but there were significant
      race/ethnic disparities at every time point. Overall, academic aspirations
      increased over time among the adolescents. Poverty was associated with poorer
      academic indicators for white youth, but not consistently for other racial/ethnic
      groups of youth. Family structure, however, was significantly associated with the
      educational indicators across all racial and ethnic groups. Despite many efforts
      to improve educational outcomes, there remain significant disparities in
      educational achievement and aspirations related to race-ethnicity and social
      status. Findings have implications for efforts to improve adolescent health at
      both individual and community levels.

PMID- 24748216
TI  - Maternal-fetal impact of vitamin D deficiency: a critical review.
AB  - Research into the extra-skeletal functions of vitamin D has been expanding in
      recent years. During pregnancy, maternal vitamin D status may be of concern
      because of the key role of this vitamin in fetal skeletal development and due to
      the association between hypovitaminosis D and adverse maternal-fetal outcomes.
      Therefore, the objective of this manuscript was to review the maternal-fetal
      impact of gestational vitamin D deficiency and the benefits of vitamin D
      supplementation during pregnancy. A literature search was performed in PubMed and
      Embase employing the following keywords: vitamin D deficiency, pregnancy, 25
      hydroxyvitamin D, and hypovitaminosis D. All relevant articles in English
      language published since 1980 were analysed by the two authors. Neonatal
      complications derived from vitamin D deficiency include low birth weight, growth
      restriction, and respiratory tract infection. In the mother, vitamin D deficiency
      has been associated with altered glucose homeostasis and increased incidence of
      gestational diabetes mellitus, pre-eclampsia, and bacterial vaginosis. However,
      the current state of the evidence is controversial for some other endpoints and
      the actual benefit of vitamin D supplementation in pregnancy remains unclear.
      Additional longitudinal studies may clarify the actual impact of vitamin D
      deficiency during pregnancy, and randomised trials are required to define the
      benefits of vitamin D supplementation in reducing the incidence of adverse
      outcomes in the mother and infant. 

PMID- 24748217
TI  - Interpreting frequency responses to dose-conserved pulsatile input signals in
      simple cell signaling motifs.
AB  - Many hormones are released in pulsatile patterns. This pattern can be modified,
      for instance by changing pulse frequency, to encode relevant physiological
      information. Often other properties of the pulse pattern will also change with
      frequency. How do signaling pathways of cells targeted by these hormones respond
      to different input patterns? In this study, we examine how a given dose of
      hormone can induce different outputs from the target system, depending on how
      this dose is distributed in time. We use simple mathematical models of
      feedforward signaling motifs to understand how the properties of the target
      system give rise to preferences in input pulse pattern. We frame these problems
      in terms of frequency responses to pulsatile inputs, where the amplitude or
      duration of the pulses is varied along with frequency to conserve input dose. We
      find that the form of the nonlinearity in the steady state input-output function
      of the system predicts the optimal input pattern. It does so by selecting an
      optimal input signal amplitude. Our results predict the behavior of common
      signaling motifs such as receptor binding with dimerization, and protein
      phosphorylation. The findings have implications for experiments aimed at studying
      the frequency response to pulsatile inputs, as well as for understanding how
      pulsatile patterns drive biological responses via feedforward signaling pathways.

PMID- 24748218
TI  - Chronic inflammation in benign prostate tissue is associated with high-grade
      prostate cancer in the placebo arm of the prostate cancer prevention trial.
AB  - BACKGROUND: Chronic inflammation is hypothesized to influence prostate cancer
      development, although a definitive link has not been established. METHODS:
      Prostate cancer cases (N = 191) detected on a for-cause (clinically indicated) or
      end-of-study (protocol directed) biopsy, and frequency-matched controls (N =
      209), defined as negative for cancer on an end-of-study biopsy, were sampled from
      the placebo arm of the Prostate Cancer Prevention Trial. Inflammation prevalence
      and extent in benign areas of biopsy cores were visually assessed using digital
      images of hematoxylin and eosin-stained sections. Logistic regression was used to
      estimate associations. RESULTS: Of note, 86.2% of cases and 78.2% of controls had
      at least one biopsy core (of three assessed) with inflammation in benign areas,
      most of which was chronic. Men who had at least one biopsy core with inflammation
      had 1.78 [95% confidence interval (CI), 1.04-3.06] times the odds of prostate
      cancer compared with men who had zero cores with inflammation. The association
      was stronger for high-grade disease (Gleason sum 7-10, N = 94; OR, 2.24; 95% CI,
      1.06-4.71). These patterns were present when restricting to cases and controls in
      whom intraprostatic inflammation was the least likely to have influenced biopsy
      recommendation because their prostate-specific antigen (PSA) was low (<2 ng/mL at
      biopsy). CONCLUSION: Inflammation, most of which was chronic, was common in
      benign prostate tissue, and was positively associated with prostate cancer,
      especially high grade. The association did not seem to be due to detection bias.
      IMPACT: This study supports an etiologic link between inflammation and prostate
      carcinogenesis, and suggests an avenue for prevention by mitigating
      intraprostatic inflammation.

PMID- 24748219
TI  - A tiered analytical approach for investigating poor quality emergency
      contraceptives.
AB  - Reproductive health has been deleteriously affected by poor quality medicines.
      Emergency contraceptive pills (ECPs) are an important birth control method that
      women can use after unprotected coitus for reducing the risk of pregnancy. In
      response to the detection of poor quality ECPs commercially available in the
      Peruvian market we developed a tiered multi-platform analytical strategy. In a
      survey to assess ECP medicine quality in Peru, 7 out of 25 different batches
      showed inadequate release of levonorgestrel by dissolution testing or improper
      amounts of active ingredient. One batch was found to contain a wrong active
      ingredient, with no detectable levonorgestrel. By combining ultrahigh performance
      liquid chromatography-ion mobility spectrometry-mass spectrometry (UHPLC-IMS-MS)
      and direct analysis in real time MS (DART-MS) the unknown compound was identified
      as the antibiotic sulfamethoxazole. Quantitation by UHPLC-triple quadrupole
      tandem MS (QqQ-MS/MS) indicated that the wrong ingredient was present in the ECP
      sample at levels which could have significant physiological effects. Further
      chemical characterization of the poor quality ECP samples included the
      identification of the excipients by 2D Diffusion-Ordered Nuclear Magnetic
      Resonance Spectroscopy (DOSY 1H NMR) indicating the presence of lactose and
      magnesium stearate. 

PMID- 24748220
TI  - The life-table demographic response of freshwater rotifer Brachionus calyciflorus
      to multi-metal (Cu, Zn, Cd, Cr, and Mn) mixture interaction.
AB  - The effects of multi-metal mixtures on the life-table demography of rotifers are
      not well known. In this study, the freshwater rotifer Brachionus calyciflorus was
      exposed to mixture of Cu, Zn, Cd, Cr, and Mn, and the life-table demographic
      parameters including net reproductive rate, generation time, life expectancy at
      hatching, and intrinsic rate of population increase were calculated. The results
      showed that interactions between a given element concentration, except Mn, and
      the other four elements mixture concentration affected the intrinsic rate of
      population increase (p < 0.01). Interactions between Zn concentration, as well as
      Mn, and the other four elements mixture concentration affected the net
      reproductive rate and the life expectancy at hatching, respectively (p < 0.05).
      The variation of parameters with the rise of the other four elements mixture
      concentrations from 0 to high was mainly attributed to the difference of
      interaction among the five metals mixture with different ratio of concentrations.

PMID- 24748221
TI  - Historical and biochemical aspects of a seventeenth century gold-based aurum
      vitae recipe.
AB  - The medicinal chemistry and biomedical applications of gold complexes have been
      intensively studied over the last decades. Some complexes have been used for the
      treatment of rheumatoid arthritis, and a considerable number of new metallodrug
      candidates have been developed as new anticancer drugs and anti-infectives.
      However, the therapeutic use of gold and its complexes goes back to ancient times
      and was also of great importance for alchemists until the modern age. In this
      report, we give an overview of the alchemic medicine between the sixteenth and
      the early eighteenth century and describe the cytotoxicity and thioredoxin
      reductase (TrxR) inhibition of a typical "aurum vitae" medicine, which was
      prepared according to a recipe by Bartholomaus Kretschmar from the seventeenth
      century. "Aurum vitae" consists of a mixture of gold, mercury and antimony
      complexes and shows the expected cytotoxic and TrxR inhibitory properties
      providing some rationale for therapeutic effects of this kind of historical
      medicinal preparation. 

PMID- 24748222
TI  - Mechanisms of iron mineralization in ferritins: one size does not fit all.
AB  - Significant progress has been made in recent years toward understanding the
      processes by which an iron mineral is deposited within members of the ferritin
      family of 24mer iron storage proteins, enabled by high-resolution structures
      together with spectroscopic and kinetic studies. These suggest common
      characteristics that are shared between ferritins, namely, a highly symmetric
      arrangement of subunits that provides a protein coat around a central cavity in
      which the mineral is formed, channels through the coat that facilitate ingress
      and egress of ions, and catalytic sites, called ferroxidase centers, that drive
      Fe(2+) oxidation. They also reveal significant variations in both structure and
      mechanism amongst ferritins. Here, we describe three general types of
      structurally distinct ferroxidase center and the mechanisms of mineralization
      that they are associated with. The highlighted variation leads us to conclude
      that there is no universal mechanism by which ferritins function, but instead
      there exists several distinct mechanisms of ferritin iron mineralization.

PMID- 24748224
TI  - The cholinergic system of the preoptic-anterior hypothalamic areas regulates the
      ovarian follicular population in an asymmetric way.
AB  - Atropine implants in the preoptic-anterior hypothalamic areas (POA-AHA) block
      ovulation. The blocking effects depend on the side of POA-AHA and the day of the
      estrous cycle in which the implants are inserted. Since ovulation is the result
      of the growth and differentiation of ovarian follicles, the purpose of this study
      was to analyze the changes in follicular and atresia population in the ovaries of
      non-ovulating rats resulting from the unilateral atropine implants in the POA
      AHA. Groups of cyclic rats were implanted with atropine or cholesterol (sham
      treatment group) in the left (diestrus-1, diestrus-2) or the right side (estrus,
      diestrus-1) of the POA-AHA. The animals were sacrificed on the expected proestrus
      or estrus day, and the follicular population was counted and the follicles
      measured in both ovaries. Atropine implants inserted in the left POA-AHA on
      diestrus-2 resulted in lower follicular growth and atresia in the ipsilateral
      ovary (left one). No apparent effects were observed in the right ovary. Atropine
      implants inserted in the right POA-AHA on estrus day resulted in fewer numbers of
      small follicles in the ipsilateral ovary (right) and a greater number of pre
      ovulatory ones. Present results suggest that acetylcholine, via muscarinic
      receptors of the POA-AHA, regulates ovarian follicular fate in an asymmetric way,
      and that its actions fluctuate during the estrous cycle. In addition, each ovary
      seems to respond differently to the POA-AHA's muscarinic signal surge on estrus
      and diestrus-2 days.

PMID- 24748223
TI  - Biological consequences of zinc deficiency in the pathomechanisms of selected
      diseases.
AB  - From many points of view, zinc is one of the most important trace elements in
      biological systems. Many articles describe the well-known role of this metal in
      human physiology and pathophysiology, but in the related literature, there is a
      lack of current and reliable reviews of the role of zinc deficiency in many
      diseases. In this article, we describe the role of zinc deficiency in the
      oxidative stress control, immune response, proliferation, and pathogenesis and
      pathophysiology of selected diseases such as depression, cardiovascular diseases,
      diabetes mellitus, Alzheimer's disease, and Wilson's disease. 

PMID- 24748226
TI  - Identification of novel and conserved microRNAs related to drought stress in
      potato by deep sequencing.
AB  - MicroRNAs (miRNAs) are a group of small, non-coding RNAs that play important
      roles in plant growth, development and stress response. There have been an
      increasing number of investigations aimed at discovering miRNAs and analyzing
      their functions in model plants (such as Arabidopsis thaliana and rice). In this
      research, we constructed small RNA libraries from both polyethylene glycol (PEG
      6,000) treated and control potato samples, and a large number of known and novel
      miRNAs were identified. Differential expression analysis showed that 100 of the
      known miRNAs were down-regulated and 99 were up-regulated as a result of PEG
      stress, while 119 of the novel miRNAs were up-regulated and 151 were down
      regulated. Based on target prediction, annotation and expression analysis of the
      miRNAs and their putative target genes, 4 miRNAs were identified as regulating
      drought-related genes (miR811, miR814, miR835, miR4398). Their target genes were
      MYB transcription factor (CV431094), hydroxyproline-rich glycoprotein (TC225721),
      quaporin (TC223412) and WRKY transcription factor (TC199112), respectively.
      Relative expression trends of those miRNAs were the same as that predicted by
      Solexa sequencing and they showed a negative correlation with the expression of
      the target genes. The results provide molecular evidence for the possible
      involvement of miRNAs in the process of drought response and/or tolerance in the
      potato plant. 

PMID- 24748227
TI  - Evaluation of endoscopic transpapillary brushing cytology for the diagnosis of
      bile duct cancer based on the histopathologic findings.
AB  - BACKGROUND AND AIM: Diagnosis of the bile duct cancer still needs more accuracy.
      Studies on endoscopic retrograde cholangiopancreatography (ERCP)-guided brushing
      cytology were carried to evaluate the role of the endoscopic transpapillary
      brushing cytology for the diagnosis of bile duct cancer. PATIENTS AND METHOD: The
      study involved 76 consecutive patients who underwent ERCP-guided bile duct
      cytology for the diagnosis of bile duct cancer from 2008 to August 2012. Three
      types of cytological specimens were obtained using different sampling methods,
      i.e., bile aspiration cytology (BAC), brush tip cytology (BTC), and post brushing
      bile cytology (PBC), to investigate their diagnostic abilities, and comparatively
      studied with each macroscopic type of the surgically resected specimens. RESULTS:
      The cancer-positive rate was 67.1 % (BAC alone: 41.9 %), and the use of BTC and
      PBC in addition to BAC yielded a statistically significant increase of the cancer
      positive rate (p = 0.0031). In 34 resected cases, the cancer-positive rate in
      relation to the macroscopic type was improved by the addition of BTC and PBC to
      BAC alone for the papillary (87.5 vs. 40.0 %, p = 0.071) and nodular (100 vs.
      70.0 %, p = 0.0603) types, but not for the flat type (62.5 vs. 57.1 %; p =
      0.7651). CONCLUSION: The diagnostic ability of ERCP-guided brushing cytology
      could be improved by the addition of PBC. However, the cancer-positive rate was
      the lowest for the flat type of bile duct cancer.

PMID- 24748228
TI  - Rescue bowel preparation: same day 2 L polyethylene glycol addition, not superior
      to bisacodyl addition 7 days later.
AB  - BACKGROUND: The optimal colon-cleansing method after failure of bowel preparation
      (BP) for colonoscopy has not been established. AIMS: We aimed to compare BP
      rescue methods after failed initial BP and to identify risk factors for rescue BP
      failure. METHODS: Eighty-five patients with BP failure after 4 L polyethylene
      glycol (PEG) ingestion were prospectively enrolled from March 2008 to March 2012.
      A second colonoscopy was performed either on the same day after ingestion of
      another 2 L PEG (group A) or 1 week later after ingestion of 4 L PEG plus 20 mg
      oral bisacodyl (group B). Differences between groups in terms of BP quality and
      risk factors for a poor BP on the second colonoscopy were investigated. RESULTS:
      Median patient age was 59 years, 45 were male (52.9 %), and 17 (20 %) had poor BP
      on the second colonoscopy. For group B, the multivariable-adjusted odds ratio
      (OR) for poor BP on the second colonoscopy relative to group A was 0.68 (95 %
      confidence interval [CI], 0.16-2.95). Adequately ingested PEG during the initial
      colonoscopy was associated with poor BP on the second colonoscopy (OR 4.05; 95 %
      CI 1.04-15.75). The two groups had similar patient discomfort rates during the
      second BP. CONCLUSIONS: The two groups did not differ in rescue BP failure rate.
      Initial BP failure after adequate consumption of 4 L PEG may be a risk factor for
      rescue BP failure. A stricter BP regimen should be considered for these patients.

PMID- 24748229
TI  - Getting the dead out: modern treatment strategies for necrotizing pancreatitis.

PMID- 24748230
TI  - Gastrointestinal manifestations of breast cancer metastasis.

PMID- 24748231
TI  - The use of double lasso, fully covered self-expandable metal stents with new
      "anchoring flap" system in the treatment of benign biliary diseases.
AB  - BACKGROUND: Many benign biliary diseases (BBD) can be treated with fully covered,
      self-expandable metal stents (FCSEMS) but stent migration occurs in up to 35.7 %.
      The aim of this study was to prospectively assess the rate of, safety and
      effectiveness and stent migration of a new biliary FCSEMS with an anti-migration
      flap (FCSEMS-AF) in patients with BBD. PATIENTS AND METHODS: This was a
      prospective study from four Italian referral endoscopy centers of 32 consecutive
      patients (10 females and 22 males; mean age: 60.1 +/- 14.8 years; range: 32-84
      years) with BBD who were offered endoscopic placement of a FCSEMS-AF as first
      line therapy. RESULTS: Were 24 strictures and 8 leaks. Stent placement was
      technically successful in 32/32 patients (100 %). Immediate clinical improvement
      was seen in all 32 patients (100 %). One late stent migration occurred (3.3 %).
      FCSEMS-AF were removed from 30 of the 32 patients (93.7 %) at a mean (+/- SD) of
      124.4 +/- 84.2 days (range: 10-386 days) after placement. All patients remained
      clinically and biochemically well at 1- and 3-month follow-up. One patient (3.3
      %) with a post-laparoscopic cholecystectomy stricture developed distal stent
      migration at 125 days. CONCLUSION: This new FCSEMS with anti-migration flap seems
      to be a safe and effective first-line treatment option for patients with BBD.

PMID- 24748232
TI  - Translation and validation of the German version of the foot and ankle outcome
      score.
AB  - PURPOSE: Outcome assessment is critical in evaluating the efficacy of orthopaedic
      procedures. The Foot and Ankle Outcome Score (FAOS) is a 42-item questionnaire
      divided into five subscales, which has been validated in several languages.
      Germany has no validated outcome score for general foot and ankle pathology. The
      aim of this study was to develop a German version of the FAOS and to investigate
      its psychometric properties. MATERIALS AND METHODS: Forward and backward
      translation was executed according to official guidelines. The final version of
      the FAOS was investigated in 150 patients with various foot and ankle disorders.
      All patients completed the FAOS, Short Form-36, numeric rating scales for pain
      and disability, and the Hannover questionnaire. The FAOS was re-administered
      after 1 week. Test-retest reliability, internal consistency, minimal detectable
      change, construct validity, and floor and ceiling effects were analyzed. RESULTS:
      Test-retest reliability and internal consistency of each subscale were excellent
      (intraclass correlation coefficient, 0.88-0.95; Cronbach's alpha, 0.94-0.98). The
      minimal detectable changes of each subscale were 17.1-20.8 at the individual
      level and 2.0-2.4 at group level. There were moderate to strong correlations
      between FAOS subscales and physical outcomes and low to moderate correlations
      between FAOS subscales and mental outcomes. Floor and ceiling effects were not
      present. CONCLUSION: The German version of the FAOS is a reliable and valid
      instrument for use in foot and ankle patients.

PMID- 24748233
TI  - The influence of between-farm distance and farm size on the spread of classical
      swine fever during the 1997-1998 epidemic in The Netherlands.
AB  - As the size of livestock farms in The Netherlands is on the increase for economic
      reasons, an important question is how disease introduction risks and risks of
      onward transmission scale with farm size (i.e. with the number of animals on the
      farm). Here we use the epidemic data of the 1997-1998 epidemic of Classical Swine
      Fever (CSF) Virus in The Netherlands to address this question for CSF risks. This
      dataset is one of the most powerful ones statistically as in this epidemic a
      total of 428 pig farms where infected, with the majority of farm sizes ranging
      between 27 and 1750 pigs, including piglets. We have extended the earlier models
      for the transmission risk as a function of between-farm distance, by adding two
      factors. These factors describe the effect of farm size on the susceptibility of
      a 'receiving' farm and on the infectivity of a 'sending' farm (or 'source' farm),
      respectively. Using the best-fitting model, we show that the size of a farm has a
      significant influence on both farm-level susceptibility and infectivity for CSF.
      Although larger farms are both more susceptible to CSF and, when infected, more
      infectious to other farms than smaller farms, the increase is less than linear.
      The higher the farm size, the smaller the effect of increments of farm size on
      the susceptibility and infectivity of a farm. Because of changes in the Dutch pig
      farming characteristics, a straightforward extrapolation of the observed farm
      size dependencies from 1997/1998 to present times would not be justified.
      However, based on our results one may expect that also for the current pig
      farming characteristics in The Netherlands, farm susceptibility and infectivity
      depend non-linearly on farm size, with some saturation effect for relatively
      large farm sizes. 

PMID- 24748234
TI  - Ameliorative effects of melatonin administration and photoperiods on diurnal
      fluctuations in cloacal temperature of Marshall broiler chickens during the hot
      dry season.
AB  - Experiments were performed with the aim of determining the effect of melatonin
      administration on diurnal fluctuations in cloacal temperature (CT) of Marshall
      broiler chickens during the hot dry season. Birds in group I (12L:12D cycle) were
      raised under natural photoperiod of 12-h light and 12-h darkness, without
      melatonin supplementation, while those in group II (LL) were kept under 24-h
      continuous lighting, without melatonin administration. Broiler chickens in group
      III (LL + melatonin) were raised under 24-h continuous lighting, with melatonin
      supplementation at 0.5 mg/kg per os. The cloacal temperatures of 15 labeled
      broiler chickens from each group were measured at 6:00, 13:00, and 19:00 h, 7
      days apart, from days 14-42. Temperature-humidity index was highest at day 14 of
      the study, with the value of 36.72 +/- 0.82  degrees C but lowest at day 28 with
      the value of 30.91 +/- 0.80  degrees C (P < 0.0001). The overall mean hourly
      cloacal temperature value of 41.51 +/- 0.03  degrees C obtained in the 12L:12D
      cycle birds was significantly higher (P < 0.001) than the value of 41.16 +/- 0.03
      degrees C recorded in the melatonin-treated group but lower than that of 41.65
      +/- 0.03  degrees C obtained in the LL birds. Mortality due to hyperthermia
      commenced at day 28 in both 12L:12D cycle and LL broiler chickens but was delayed
      till day 42 in LL + MEL broiler chickens. In conclusion, melatonin administration
      alleviated the deleterious effects of heat stress on broiler chickens by
      maintaining their cloacal temperature at relatively low values.

PMID- 24748235
TI  - Can HE4 predict platinum response during first-line chemotherapy in ovarian
      cancer?
AB  - Actually, in literature there are not valid tools able to predict the
      chemotherapy response during first-line ovarian cancer treatment. CA125 and human
      epididymis protein 4 (HE4) levels of consecutive single-institution patients with
      epithelial ovarian cancer (EOC) were measured during first-line chemotherapy and
      until 6 months follow-up. First, patients were divided into two groups according
      to a temporal criterion: patients treated during 2009 (group A: training group)
      and patients treated during 2010 (group B: verification group). At sixth months
      follow-up, patients were sub-classified, within both groups, as platinum
      resistant or platinum sensitive/intermediate, according to Response Evaluation
      Criteria in Solid Tumors criteria, and the serum marker courses were further
      analyzed in each subgroup. Moreover, we performed a logistic regression analysis
      to choose CA125 and HE4 levels that are best fitted to predict chemoresponse. A
      total of 76 patients were divided into two groups: group A (n = 42) and group B
      (n = 34). After 6 months of follow-up, 40 patients were classified as platinum
      sensitive/intermediate and 36 as platinum resistant. At third chemotherapy cycle,
      in platinum-resistant patients, HE4 levels were >70 pmol/L in 36 of 36 cases,
      although in platinum-sensitive/intermediate patients, HE4 levels were >70 pmol/L
      only in six of 40 cases (sensitivity 100 %, specificity 85 %). Moreover, HE4
      reduction of almost 47 % at third chemotherapy cycle reached the sensitivity of
      83 % with a specificity of 87 % (positive predictive value = 0.86, negative
      predictive value = 0.85) in predicting chemoresponse. On the contrary, CA125
      values during chemotherapy did not result statistically significant in predicting
      platinum response. Our findings suggest that HE4 values during first-line
      chemotherapy could predict chemotherapy response in EOC patients.

PMID- 24748236
TI  - Inhibition of EGFR-induced glucose metabolism sensitizes chondrosarcoma cells to
      cisplatin.
AB  - Chondrosarcomas are malignant cartilage-forming tumors which are resistant to
      conventional chemotherapy and radiotherapy. By searching in Oncomine which is a
      cancer microarray database and web-based data mining platform, we found Glut1 and
      LDHA were upregulated in human chondrosarcoma patient samples. In this study, we
      reported total epidermal growth factor receptor (EGFR) expression and
      phosphorylated EGFR were highly activated in human chondrosarcoma cell lines. In
      addition, overexpression of EGFR contributed to cisplatin resistance. EGFR
      promoted glucose metabolism of chondrosarcoma cells through the upregulation of
      glycolysis key enzymes. Interestingly, cisplatin-resistant chondrosarcoma cells
      showed upregulated glucose metabolism and EGFR signaling pathway. Finally, we
      demonstrated that the combination of either EGFR inhibitor or anaerobic
      glycolysis inhibitor with cisplatin showed synergistically inhibitory effects on
      cisplatin-resistant chondrosarcoma cells through the inducements of apoptosis and
      cell cycle arrest. Our project proposed a novel function of EGFR in the
      regulation of glucose metabolism in chondrosarcoma cells and contributed to the
      development of therapeutic strategies for the clinical treatment of
      chondrosarcoma patient. 

PMID- 24748237
TI  - Differential assessment of designations of wetland status using two delineation
      methods.
AB  - Two different methods are commonly used to delineate and characterize wetlands.
      The U.S. Army Corps of Engineers (ACOE) delineation method uses field observation
      of hydrology, soils, and vegetation. The U.S. Fish and Wildlife Service's
      National Wetland Inventory Program (NWI) relies on remote sensing and
      photointerpretation. This study compared designations of wetland status at
      selected study sites using both methods. Twenty wetlands from the Wetland
      Boundaries Map of the Ausable-Boquet River Basin (created using the revised NWI
      method) in the Ausable River watershed in Essex and Clinton Counties, NY, were
      selected for this study. Sampling sites within and beyond the NWI wetland
      boundaries were selected. During the summers of 2008 and 2009, wetland hydrology,
      soils, and vegetation were examined for wetland indicators following the methods
      described in the ACOE delineation manual. The study shows that the two methods
      agree at 78 % of the sampling sites and disagree at 22 % of the sites. Ninety
      percent of the sampling locations within the wetland boundaries on the NWI maps
      were categorized as ACOE wetlands with all three ACOE wetland indicators present.
      A binary linear logistic regression model analyzed the relationship between the
      designations of the two methods. The outcome of the model indicates that 83 % of
      the time, the two wetland designation methods agree. When discrepancies are
      found, it is the presence or absence of wetland hydrology and vegetation that
      causes the differences in delineation. 

PMID- 24748238
TI  - Evaluation criteria for participatory research: insights from coastal Uruguay.
AB  - Participatory research in which experts and non-experts are co-researchers in
      addressing local concerns (also known as participatory action research or
      community-based research) can be a valuable approach for dealing with the
      uncertainty of social-ecological systems because it fosters learning among
      stakeholders and co-production of knowledge. Despite its increased application in
      the context of natural resources and environmental management, evaluation of
      participatory research has received little attention. The objectives of this
      research were to define criteria to evaluate participatory research processes and
      outcomes, from the literature on participation evaluation, and to apply them in a
      case study in an artisanal fishery in coastal Uruguay. Process evaluation
      criteria (e.g., problem to be addressed of key interest to local and additional
      stakeholders; involvement of interested stakeholder groups in every research
      stage; collective decision making through deliberation; and adaptability through
      iterative cycles) should be considered as conditions to promote empowering
      participatory research. Our research contributes to knowledge on evaluation of
      participatory research, while also providing evidence of the positive outcomes of
      this approach, such as co-production of knowledge, learning, strengthened social
      networks, and conflict resolution. 

PMID- 24748240
TI  - Four types of barriers to adherence of antiretroviral therapy are associated with
      decreased adherence over time.
AB  - The objectives of this study were to understand how different types of barriers
      to adherence to antiretroviral therapy (ART) were related and their differential
      impact on objectively measured adherence over time. Data from 151 patients taking
      ART were used to describe four sub-types of self-reported adherence barriers:
      medication and health concerns (MHC), stigma (S), family responsibilities (FR),
      and problems with schedule and routine (PSR). Generalized linear models with
      generalized estimating equations (GEE) were used to examine the impact of
      barriers on adherence over time. The sample was 23 % female, mean age 42 years,
      with 26 % African-American and 20 % Hispanic. The overall average adherence was
      73 %. Patients reported at least one PSR barrier in 66 % of study visits, MHC in
      40 %, S in 17 %, and FR in 6 %. In 40 % of visits, patients reported two or more
      barrier sub-types. There were statistically significant (p <= 0.05) decreases of
      3.9, 2.5, and 2.4 in percent adherence, for MHC, PSR, and S, respectively, per
      unit increase in barrier score. Interventions to address different types of
      patient-identified barriers to ART adherence using targeted approaches are
      needed.

PMID- 24748242
TI  - Confronting pediatric brain tumors: parent stories.
AB  - This narrative symposium brings to light the extreme difficulties faced by
      parents of children diagnosed with brain tumors. NIB editorial staff and
      narrative symposium editors, Gigi McMillan and Christy A. Rentmeester, developed
      a call for stories that was distributed on several list serves and posted on
      Narrative Inquiry in Bioethics' website. The call asks parents to share their
      personal experience of diagnosis, treatment, long-term effects of treatment,
      social issues and the doctor-patient-parent dynamic that develops during this
      process. Thirteen stories are found in the print version of the journal and an
      additional six supplemental stories are published online only through Project
      MUSE. One change readers may notice is that the story authors are not listed in
      alphabetical order. The symposium editors had a vision for this issue that
      included leading readers through the timeline of this topic: diagnosis-treatment
      acute recovery-recurrence-treatment (again)-acute recovery (again)-long-term
      quality of life-(possibly) end of life. Stories are arranged to help lead the
      reader through this timeline.Gigi McMillan is a patient and research subject
      advocate, co-founder of We Can, Pediatric Brain Tumor Network, as well as, the
      mother of a child who suffered from a pediatric brain tumor. She also authored
      the introduction for this symposium. Christy Rentmeester is an Associate
      Professor of Health Policy and Ethics in the Creighton University School of
      Medicine. She served as a commentator for this issue. Other commentators for this
      issue are Michael Barraza, a clinical psychologist and board member of We Can,
      Pediatric Brain Tumor Network; Lisa Stern, a pediatrician who has diagnosed six
      children with brain tumors in her 20 years of practice; and Katie Rose, a
      pediatric brain tumor patient who shares her special insights about this world. 

PMID- 24748243
TI  - A bittersweet score: a father's account of his family's 20-year journey after a
      pediatric brain tumor diagnosis.

PMID- 24748241
TI  - Perinatal distress in women in low- and middle-income countries: allostatic load
      as a framework to examine the effect of perinatal distress on preterm birth and
      infant health.
AB  - In low- and middle-income countries (LMIC), determinants of women's and
      children's health are complex and differential vulnerability may exist to risk
      factors of perinatal distress and preterm birth. We examined the contribution of
      maternal perinatal distress on preterm birth and infant health in terms of infant
      survival and mother-infant interaction. A critical narrative and interpretive
      literature review was conducted. Peer-reviewed electronic databases (MEDLINE,
      Embase, Global Health, CINHAL), grey literature, and reference lists were
      searched, followed by a consultation exercise. The literature was predominantly
      from high-income countries. We identify determinants of perinatal distress and
      explicate changes in the hypothalamic-pituitary-adrenal axis, sympathetic, immune
      and cardiovascular systems, and behavioral responses resulting in
      pathophysiological effects. We suggest cultural-neutral composite measures of
      allostatic mediators (i.e., several biomarkers) of maternal perinatal distress as
      objective indicators of dysregulation in body systems in pregnant women in LMIC.
      Understanding causal links of maternal perinatal distress to preterm birth in
      women in LMIC should be a priority. The roles of allostasis and allostatic load
      are considered within the context of the health of pregnant women and
      fetuses/newborns in LMIC with emphasis on identifying objective indicators of the
      level of perinatal distress and protective factors or processes contributing to
      resilience while facing toxic stress. We propose a prospective study design with
      multiple measures across pregnancy and postpartum requiring complex statistical
      modeling. Building research capacity through partnering researchers in high
      income countries and LMIC and reflecting on unique ethical challenges will be
      important to generating new knowledge in LMIC.

PMID- 24748244
TI  - From normal to nightmare.

PMID- 24748245
TI  - Second guessing.

PMID- 24748246
TI  - Things are NOT okay.

PMID- 24748247
TI  - Advocates, not problem parents.

PMID- 24748248
TI  - What now?

PMID- 24748249
TI  - Down the medical rabbit hole.

PMID- 24748250
TI  - The road to understanding and acceptance of the late effects of pediatric brain
      tumors and treatment.

PMID- 24748251
TI  - Family, friends, and cancer: the overwhelming effects of brain cancer on a
      child's life.

PMID- 24748252
TI  - Over the years.

PMID- 24748253
TI  - Prepping for the day you hope never arrives: facing recurrence.

PMID- 24748254
TI  - Not the end we planned for.

PMID- 24748255
TI  - Ice cream for breakfast.

PMID- 24748256
TI  - Cartography of endurance.
AB  - This commentary canvasses a few prominent themes of ethical relevance drawn from
      the stories in this issue. I develop the metaphor of cartography to illuminate
      critical experiences in the moral lives of parents of children with brain tumors.
      Relationship transformation within families along the timeline of a child's
      illness and recovery is one such set of experiences. Points for consideration in
      health professions education are also featured: clinical humility regarding
      "second opinions," cultivating therapeutic efficacy from the clinician-parent
      relationship, error, and medical care itself as a source of trauma. 

PMID- 24748257
TI  - The right thing.
AB  - In my hospital experience working with families of seriously ill children,
      parents describe being stripped of confidence and having their functioning so
      compromised that they are unable to process facts or initiate action in a
      meaningful way. These narratives offer a glimpse into the minds of these parents
      and two things are clear: they love their children and they want to do the right
      thing. Treatment for pediatric brain tumors can last for long periods of time
      (months, even years) and cause significant damage even while seeking to save the
      child's life. Over the course of time, the family dynamic changes. Several
      important themes emerge from these stories and are explored in this commentary.
      An overarching theme is the agony that these parents go through as they struggle
      to make life and death decisions on behalf of their children. 

PMID- 24748258
TI  - "Grey matters".
AB  - It's common in this world, for diagnoses to be confused. This grey, oblique world
      is the "World of Brain Tumors" from which these narratives are written, a world I
      entered when a tangerine-sized tumor was found on my temporal lobe. Each
      narrative illustrates this world in which everything is covered in a thick film
      rendering things once obvious, now unknown. Parents are asked to choose treatment
      plans for their children, plans that will inevitably alter their child's quality
      of life but in ways they cannot determine or even imagine. Parents are asked to
      play God. Most of the parents who share their stories in this collection, parents
      of PBT (pediatric brain tumor) patients have to walk the line of trying to not
      disrupt their relationships with their physicians, wanting the best for their
      child, and facing the decision to follow their gut or go with advised treatment
      plans. 

PMID- 24748259
TI  - Reflecting on parental concerns in the treatment of pediatric brain tumors:
      observations from a general pediatrician.
AB  - This issue of Narrative Inquiry in Bioethics explores the concerns and point of
      view of parents who have had to confront the devastating diagnosis of a pediatric
      brain tumor. This commentary, written by a general pediatrician, is a synthesis
      of several narrative themes which touch on a range of topics from relapse to long
      term sequelae and other issues that effect a growing population of pediatric
      brain tumor patients. It offers a glimpse into the problems that need to be
      addressed by health professionals, educators and support teams who provide short
      and long term care to these patients and their families. 

PMID- 24748260
TI  - Who are you going to call? Primary care patients' disclosure decisions regarding
      direct-to-consumer genetic testing.
AB  - BACKGROUND: Direct-to-consumer genetic testing (DTCGT) offers risk estimates for
      a variety of complex diseases and conditions, yet little is known about its
      impact on actual users, including their decisions about sharing the information
      gleaned from testing. Ethical considerations include the impact of unsolicited
      genetic information with variable validity and clinical utility on relatives, and
      the possible burden to the health care system if revealed to physicians. AIMS:
      The qualitative study explored primary care patients' views, attitudes, and
      decision making considerations regarding DTCGT. This article focuses on the
      disclosure decisions participants made regarding participation, testing, and
      results of DTCGT, a topic which arose as a secondary aim of the study. METHODS:
      Through four longitudinal interviews (pre-test, results, 3 and 12 months post
      test) we examined twenty primary care patients' decisions, expressed intentions,
      and actions regarding disclosure to immediate and extended family, friends and
      coworkers, and physicians about participation in and results of DTCGT. Individual
      interviews were analyzed using qualitative content analysis and a summative
      approach to describe the global themes. RESULTS: Most participants disclosed to
      some immediate family; less than half disclosed to extended family; approximately
      half talked to friends. Most participants stated they would or might disclose to
      physicians about DTCGT and a few did. Conceptual themes that emerged from the
      data analysis include ambivalence about disclosure, consistency between intention
      and actual disclosure behavior and decisions, and conditional information
      sharing. CONCLUSIONS: Participants' intentional and actual disclosure patterns
      offer insight into how they view DTCGT, weigh results, and the potential impact
      of DTCGT.

PMID- 24748261
TI  - I don't know why I called you.
AB  - This case study details a request from a patient family member who calls our
      service without an articulated ethical dilemma. The issue that arose involved the
      conflict between continuing further medical interventions versus transitioning to
      supportive or palliative care and transferring the patient home. Beyond the
      resolution of the ethical dilemma, this narrative illustrates an approach to
      ethics consultation that seeks practical resolution of ethical dilemmas in
      alignment with patient goals and values. Importantly, the family's suffering is
      addressed through a relationship driven, humanistic approach that incorporates
      elements of compassion, empathy and dialog. 

PMID- 24748262
TI  - Responding to the refusal of care in the emergency department.
AB  - The emergency department (ED) serves as the primary gateway for acute care and
      the source of health care of last resort. Emergency physicians are commonly
      expected to rapidly assess and treat patients with a variety of life-threatening
      conditions. However, patients do refuse recommended therapy, even when the
      consequences are significant morbidity and even mortality. This raises the
      ethical dilemma of how emergency physicians and ED staff can rapidly determine
      whether patient refusal of treatment recommendations is based on intact decision
      making capacity and how to respond in an appropriate manner when the declining of
      necessary care by the patient is lacking a basis in informed judgment. This
      article presents a case that illustrates the ethical tensions raised by the
      refusal of life-sustaining care in the ED and how such situations can be
      approached in an ethically appropriate manner. 

PMID- 24748263
TI  - Ethan's gift.

PMID- 24748264
TI  - How I hate you, cancer.

PMID- 24748265
TI  - Life in limbo.

PMID- 24748266
TI  - My lost survivor.

PMID- 24748267
TI  - An encounter with the art and science of medicine.

PMID- 24748268
TI  - Roadmap needed: how to help parents navigate the worst day of their lives.

PMID- 24748269
TI  - Editors' note.

PMID- 24748270
TI  - Transcultural adaptation of the Korean version of the Hip Outcome Score.
AB  - PURPOSE: The Hip Outcome Score (HOS) is a questionnaire commonly used to assess
      the clinical outcome of patients after hip arthroscopy. However, a Korean version
      of the HOS is not available. The aim of this study was to translate and adapt the
      HOS questionnaire into the Korean language and then assess the psychometric
      properties of this instrument. METHODS: Translation and transcultural adaptation
      of the HOS into Korean (HOS-K) was performed in accordance with the international
      recommendations. Sixty patients (mean age 38.4 years) planning hip arthroscopy
      participated in evaluating the psychometric properties of the HOS-K. Psychometric
      analyses consisted of assessing for the following: (1) floor/ceiling effects, (2)
      internal consistency using Cronbach's alpha, (3) test-retest reliability over 2-3
      weeks with intraclass correlation coefficient (ICC), (4) convergent validity by
      correlation with the SF-36 and Hip disability and Osteoarthritis Outcome Score
      (HOOS), (5) construct validity by assessing for a difference in HOS-K scores
      based on a rating of hip function, and (6) responsiveness with a change in score
      over a 6-month period. RESULTS: The English version of the HOS was translated and
      adapted to Korean without notable discrepancies. The HOS-K scores were reliable
      with ICC of 0.946 for the activities of daily living (ADL) subscale and 0.929 for
      the sports subscale. Internal consistency was confirmed by Cronbach's alpha >0.90
      for both subscales. Both subscales had a strong correlation to the five subscales
      of SF-36, except the general health subscale. The ADL subscale showed strong
      correlations with all the subscales of the HOOS, and sports subscale showed
      strong correlations with all subscales of the HOOS, except the symptom subscales
      of HOOS. The HOS-K also demonstrated evidence for responsiveness without floor
      and ceiling effects. CONCLUSION: The HOS-K can be recommended as an outcome
      instrument in hip arthroscopy for Korean-speaking individuals. Surgeons can use
      the HOS-K to evaluate the outcome of hip arthroscopy in Korea. LEVEL OF EVIDENCE:
      Therapeutic case series with no comparison group, Level IV.

PMID- 24748271
TI  - Results of surgical treatment of calcaneus insertional tendinopathy in middle-
      and long-distance runners.
AB  - PURPOSE: Calcaneus insertional tendinopathy in runners is common and involves
      important therapeutic controversies. The object of this study was to determine
      the delay and level of return to sport after insertional surgery in runners, with
      and without tendon damage. METHODS: Eighteen runners underwent surgery for
      insertional calcaneus tendinopathy. Nine required an exostosectomy/bursectomy,
      and nine others required a tendon reinsertion/autograft. All patients were
      clinically assessed pre- and post-operatively with AOFAS scores and post
      operatively with ATRS. This series included analysis of "pure conflicts" and
      "severe insertional lesion" scores. If the insertional tendon was free or the
      lesion was smaller than 50 %, the group was classified as "pure conflict/minor
      tendon damage". In the situation in which a loss of tendon occurred or the tendon
      lesion was greater than 50 %, the group was classified as "major tendon damage".
      Pre-operatively, the AOFAS "overall", "pure conflicts/minor tendon damage" and
      "major tendon damage" groups' scores were 58.5 +/- 15, 68.2 +/- 8.8 and 48.9 +/-
      13.9/100, respectively. RESULTS: Post-operatively, the AOFAS "overall", "pure
      conflicts/minor tendon" and "major tendon damage" groups' scores were 93.7 +/-
      8.2, 93.2 +/- 10.2 and 95.2 +/- 5.7/100, respectively. The AOFAS score gain for
      each group was, respectively, 35.2 +/- 19, 24 +/- 17 and 46.3 +/- 14.1. The ATRS
      "overall", "pure conflicts/minor tendon damage" and "major tendon damage" groups'
      scores were 81.5 +/- 14.9, 78.3 +/- 20.1 and 84.7 +/- 6.7/100, respectively. The
      global sport recovery delay was 9.3 +/- 4.1 months; it was 6 +/- 3.3 months for
      the pure conflict/minor tendon damage subgroup and 10 +/- 4.6 months for the
      severe tendon damages subgroup. CONCLUSION: Achilles insertional tendinopathy
      surgery on this population results in few complications with good functional
      results if the surgical technique is adapted to the type of tendon injury. The
      clinical relevance of this study is that it highlights the various forms of
      calcaneus insertional tendinopathy and various treatment options. The authors
      show that in the case of major tendon damage, time to return to sport is longer.

PMID- 24748272
TI  - The role of backbone hydrogen bonds in the transition state for protein folding
      of a PDZ domain.
AB  - Backbone hydrogen bonds are important for the structure and stability of
      proteins. However, since conventional site-directed mutagenesis cannot be applied
      to perturb the backbone, the contribution of these hydrogen bonds in protein
      folding and stability has been assessed only for a very limited set of small
      proteins. We have here investigated effects of five amide-to-ester mutations in
      the backbone of a PDZ domain, a 90-residue globular protein domain, to probe the
      influence of hydrogen bonds in a beta-sheet for folding and stability. The amide
      to-ester mutation removes NH-mediated hydrogen bonds and destabilizes hydrogen
      bonds formed by the carbonyl oxygen. The overall stability of the PDZ domain
      generally decreased for all amide-to-ester mutants due to an increase in the
      unfolding rate constant. For this particular region of the PDZ domain, it is
      therefore clear that native hydrogen bonds are formed after crossing of the rate
      limiting barrier for folding. Moreover, three of the five amide-to-ester mutants
      displayed an increase in the folding rate constant suggesting that the hydrogen
      bonds are involved in non-native interactions in the transition state for
      folding. 

PMID- 24748273
TI  - Pathological features of the sessile serrated adenoma/polyp with special
      references of its carcinogenesis.
AB  - The sessile serrated adenoma/polyp (SSA/P) has been thought as the relatively new
      precursor for the colorectal cancer. In the current review, the well-known
      pathological features including the histological definition of the SSA/P are
      described using the previous reports. Although the SSA/P is thought one of pre
      cancerous lesions of the colorectal carcinoma, the decisive or documentary lesion
      like "carcinoma in adenoma" is very rare. In this review, the strict case of the
      carcinoma derived from the SSA/P is demonstrated using our cases. Although the
      genetic investigations of the SSA/P have shown the new pathway of colorectal
      carcinogenesis and these concepts are thought to be almost right, the
      verification for them should be performed using "the carcinoma in SSA/P" like the
      present case. 

PMID- 24748274
TI  - Human immunodeficiency virus type 1 (HIV-1) subtype B epidemic in Panama is
      mainly driven by dissemination of country-specific clades.
AB  - The Human immunodeficiency virus type-1 (HIV-1) subtype B is the most predominant
      clade in Central America; but information about the evolutionary history of this
      virus in this geographic region is scarce. In this study, we reconstructed the
      spatiotemporal and population dynamics of the HIV-1 subtype B epidemic in Panama.
      A total of 761 HIV-1 subtype B pol sequences obtained in Panama between 2004 and
      2013 were combined with subtype B pol sequences from the Americas and Europe.
      Maximum Likelihood phylogenetic analyses revealed that HIV-1 subtype B infections
      in Panama derived from the dissemination of multiple founder viruses. Most
      Panamanian subtype B viruses (94.5%) belong to the pandemic viral strain proposed
      as originated in the US, whereas others (5.5%) were intermixed among non-pandemic
      Caribbean strains. The bulk (76.6%) of subtype B sequences from Panama grouped
      within 12 country-specific clades that were not detected in other Central
      American countries. Bayesian coalescent-based analyses suggest that most
      Panamanian clades probably originated between the early 1970s and the early
      1980s. The root location of major Panamanian clades was traced to the most
      densely populated districts of Panama province. Major Panamanian clades appear to
      have experienced one or two periods of exponential growth of variable duration
      between the 1970s and the 2000s, with median growth rates from 0.2 to 0.4 year(
      1). Thus, the HIV-1 subtype B epidemic in Panama is driven by the expansion of
      local viral strains that were introduced from the Caribbean and other American
      countries at an early stage of the AIDS pandemic.

PMID- 24748275
TI  - Stroke risk factors in an incident population in urban  and rural Tanzania: a
      prospective, community-based,  case-control study.
AB  - BACKGROUND: The burden of stroke on health systems in low-income and middle
      income countries is increasing. However, high-quality data for modifiable stroke
      risk factors in sub-Saharan Africa are scarce, with no community based, case
      control studies previously published. We aimed to identify risk factors for
      stroke in an incident population from rural and urban Tanzania. METHODS: Stroke
      cases from urban Dar-es-Salaam and the rural Hai district were recruited in a
      wider study of stroke incidence between June 15, 2003, and June 15, 2006. We
      included cases with fi rst-ever and recurrent stroke. Community-acquired controls
      recruited from the background census populations of the two study regions were
      matched with cases for age and sex and were interviewed and assessed. Data
      relating to medical and social history were recorded and blood samples taken.
      FINDINGS: We included 200 stroke cases (69 from Dar-es-Salaam and 131 from Hai)
      and 398 controls (138 from Dar-es-Salaam and 260 from Hai). Risk factors were
      similar at both sites, with previous cardiac event (odds ratio [OR] 7.39, 95% CI
      2.42-22.53; p<0.0001), HIV infection (5.61, 2.41-13.09; p<0.0001), a high ratio
      of total cholesterol to HDL cholesterol (4.54, 2.49-8.28; p<0.0001), smoking
      (2.72, 1.49-4.96; p=0.001), and hypertension (2.14, 1.09-4.17; p=0.026)
      identified as significant independent risk factors for stroke. In Hai, additional
      risk factors of diabetes (4.04, 1.29-12.64) and low HDL cholesterol (9.84, 4.06
      23.84) were also significant. INTERPRETATION: We have identified many of the risk
      factors for stroke already reported for other world regions. HIV status was an
      independent risk factor for stroke within an antiretroviral-naive population.
      Clinicians should be aware of the increased risk of stroke in people with HIV,
      even in the absence of antiretroviral treatment.

PMID- 24748276
TI  - Targeting c-Met receptor overcomes TRAIL-resistance in brain tumors.
AB  - Tumor necrosis factor related apoptosis-inducing ligand (TRAIL) induced apoptosis
      specifically in tumor cells. However, with approximately half of all known tumor
      lines being resistant to TRAIL, the identification of TRAIL sensitizers and their
      mechanism of action become critical to broadly use TRAIL as a therapeutic agent.
      In this study, we explored whether c-Met protein contributes to TRAIL
      sensitivity. We found a direct correlation between the c-Met expression level and
      TRAIL resistance. We show that the knock down c-Met protein, but not inhibition,
      sensitized brain tumor cells to TRAIL-mediated apoptosis by interrupting the
      interaction between c-Met and TRAIL cognate death receptor (DR) 5. This
      interruption greatly induces the formation of death-inducing signaling complex
      (DISC) and subsequent downstream apoptosis signaling. Using intracranially
      implanted brain tumor cells and stem cell (SC) lines engineered with different
      combinations of fluorescent and bioluminescent proteins, we show that SC
      expressing a potent and secretable TRAIL (S-TRAIL) have a significant anti-tumor
      effect in mice bearing c-Met knock down of TRAIL-resistant brain tumors. To our
      best knowledge, this is the first study that demonstrates c-Met contributes to
      TRAIL sensitivity of brain tumor cells and has implications for developing
      effective therapies for brain tumor patients. 

PMID- 24748277
TI  - Maori heads (mokomokai): the usefulness of a complete forensic analysis
      procedure.
AB  - Based on an analysis of 19 mummified Maori heads (mokomokai) referred to our
      forensic laboratory for anthropological analysis prior to their official
      repatriation from France to New Zealand, and data from the anthropological and
      medical literature, we propose a complete forensic procedure for the analysis of
      such pieces. A list of 12 original morphological criteria was developed. Items
      included the sex, age at death, destruction of the skull base, the presence of
      argil deposits in the inner part of the skull, nostrils closed with exogenous
      material, sewing of eyelids and lips, pierced earlobes, ante-mortem and/or post
      mortem tattoos, the presence of vegetal fibers within nasal cavities, and other
      pathological or anthropological anomalies. These criteria were tested for all 19
      mokomokai repatriated to New Zealand by the French authorities. Further
      complementary analyses were limited to fiberscopic examination of the
      intracranial cavities because of the taboo on any sampling requested by the Maori
      authorities. In the context of global repatriation of human artifacts to native
      communities, this type of anthropological expertise is increasingly frequently
      requested of forensic anthropologists and other practitioners. We discuss the
      reasons for and against repatriating non-authentic artifacts to such communities
      and the role played by forensic anthropologists during the authentication
      process. 

PMID- 24748278
TI  - Comparative study on pharmacokinetics of a series of anticholinergics, atropine,
      anisodamine, anisodine, scopolamine and tiotropium in rats.
AB  - The compound series of traditional anticholinergics [atropine (Atr), anisodamine
      (Ani), anisodine (AT3), and scopolamine (Sco)], naturally occurring belladonna
      alkaloid, have been approved for numerous therapeutic uses since 1970s.
      Tiotropium, a novel M receptor antagonist for the treatment of chronic
      obstructive pulmonary disease, was structurally modified based on atropine-like
      drugs. Clinical phenomena suggested that the changes of substituent group were
      related to the pharmacokinetic and pharmacodynamic characteristics of the agents.
      In an attempt to compare the pharmacokinetics of the series of anticholinergics
      and investigate the subsets motivating selective anticholinergic potencies, a
      sensitive LC-MS/MS method was established to analyze the differences of
      pharmacokinetic parameters. In this paper, we determined the pharmacokinetics of
      atropine, anisodamine, anisodine, scopolamine, and tiotropium after i.v. and i.g.
      single dose administration. After i.v. administration, the maximum drug plasma
      concentrations (C max) of Atr, Ani, AT3, and Sco were 274.25 +/- 53.66, 267.50 +/
      33.16, 340.50 +/- 44.52, and 483.75 +/- 78.13 ng/mL. Tiotropium had a slightly
      higher area under the curve with a significant increase of C max value. Because
      of their partial solubility, Atr, Ani, AT3, and Sco had different bioavailability
      in rats of 21.62, 10.78, 80.45 and 2.52 %, respectively. Following i.g.
      administration of tiotropium, the C max value below 20 ng/mL revealed the very
      low oral absorption. The urinary excretion rates of Atr, Ani, AT3, Sco and
      tiotropium were 11.33, 54.86, 32.67, 8.69 and 73.91 %. This work provided
      relatively comprehensive preclinical data on the series of anticholinergics,
      which may be used to explain the clinical adverse effects and applications. 

PMID- 24748279
TI  - Decreased resting functional connectivity after traumatic brain injury in the
      rat.
AB  - Traumatic brain injury (TBI) contributes to about 10% of acquired epilepsy. Even
      though the mechanisms of post-traumatic epileptogenesis are poorly known, a
      disruption of neuronal networks predisposing to altered neuronal synchrony
      remains a viable candidate mechanism. We tested a hypothesis that resting state
      BOLD-fMRI functional connectivity can reveal network abnormalities in brain
      regions that are connected to the lesioned cortex, and that these changes
      associate with functional impairment, particularly epileptogenesis. TBI was
      induced using lateral fluid-percussion injury in seven adult male Sprague-Dawley
      rats followed by functional imaging at 9.4T 4 months later. As controls we used
      six sham-operated animals that underwent all surgical operations but were not
      injured. Electroencephalogram (EEG)-functional magnetic resonance imaging (fMRI)
      was performed to measure resting functional connectivity. A week after functional
      imaging, rats were implanted with bipolar skull electrodes. After recovery, rats
      underwent pentyleneterazol (PTZ) seizure-susceptibility test under EEG. For image
      analysis, four pairs of regions of interests were analyzed in each hemisphere:
      ipsilateral and contralateral frontal and parietal cortex, hippocampus, and
      thalamus. High-pass and low-pass filters were applied to functional imaging data.
      Group statistics comparing injured and sham-operated rats and correlations over
      time between each region were calculated. In the end, rats were perfused for
      histology. None of the rats had epileptiform discharges during functional
      imaging. PTZ-test, however revealed increased seizure susceptibility in injured
      rats as compared to controls. Group statistics revealed decreased connectivity
      between the ipsilateral and contralateral parietal cortex and between the
      parietal cortex and hippocampus on the side of injury as compared to sham
      operated animals. Injured animals also had abnormal negative connectivity between
      the ipsilateral and contralateral parietal cortex and other regions. Our data
      provide the first evidence on abnormal functional connectivity after experimental
      TBI assessed with resting state BOLD-fMRI. 

PMID- 24748280
TI  - Depressive symptomatology and quality of life assessment among women using the
      levonorgestrel-releasing intrauterine system: an observational study.
AB  - OBJECTIVE: The aim of our study was to examine the effect of the levonorgestrel
      releasing intrauterine system (LNG-IUS) treatment on depressive symptoms, changes
      in bleeding patterns, and quality of life (QoL) among premenopausal women in our
      clinic. MATERIALS AND METHODS: We recruited 120 premenopausal women, aged 18-50
      years, who had sought care in the previous year for menorrhagia. LNG-IUS was
      inserted into eligible patients after the relevant evaluations. Both
      questionnaires were administered at time of the initial screening before and 6
      months after insertion of the LNG-IUS. All patients completed the 36-item Short
      Form Health Survey (SF-36) for QoL and Beck's Depression Inventory for depressive
      symptoms. RESULTS: At the 6-month follow-up visit, the pictorial blood assessment
      chart score (PBAC) considerably decreased (p < 0.001). For SF-36 scores, physical
      functioning, physical role limitations, emotional role limitations, bodily pain,
      vitality, and mental health scores improved significantly after treatment (p <
      0.001). Depression scores showed no significant difference from baseline to 6
      months (p = 0.375). CONCLUSION: The LNG-IUS for the treatment of menorrhagia
      increases the QoL, and depression scores did not increase significantly in 6
      months.

PMID- 24748281
TI  - Transient intrauterine fluid accumulation not due to hydrosalpinx or any
      identifiable pelvic pathology is not detrimental to IVF outcome.
AB  - PURPOSE: This study is to assess whether transient intrauterine fluid
      accumulation (IUFA) first noted during controlled ovarian hyperstimulation that
      does not persist on the day of embryo transfer not due to any identifiable pelvic
      pathology has any detrimental effect on in vitro fertilization (IVF) outcome.
      METHODS: From a database of 16,900 cycles, 144 patients with transient
      "physiological" IUFA were recruited. Four hundred fifty-one consecutive patients
      who had male factor infertility served as the control group. The amount of IUFA
      classified as largest dimension in the antero-posterior (AP) plane; <=2, 3-5 or
      >5 mm. RESULTS: The mean female age, the mean number of embryos transferred and
      endometrial thickness on the day of hCG administration were comparable among the
      study and control groups. Similarly, clinical pregnancy, ongoing pregnancy and
      implantation rates were comparable among the study and control groups. Female age
      was noted to be the only significant independent predictor of ongoing pregnancy.
      The AP dimension of IUFA did not have any impact on pregnancy and implantation
      rates. CONCLUSIONS: Transient IUFA not due to hydrosalpinx or any identifiable
      pelvic pathology has no detrimental effect on IVF pregnancy rates. Hence, cycle
      cancellation should be avoided in such cycles.

PMID- 24748282
TI  - Increased adhesion formation after gelatin-thrombin matrix application in a rat
      model.
AB  - PURPOSE: To evaluate the effects of gelatin matrix and thrombin-based hemostatic
      sealant agents (gelatin-thrombin matrix) on postoperative adhesion formation in
      the rat uterine horn model. METHODS: A total of fourteen female Wistar-Albino
      rats were used in our postoperative adhesion formation model. Both uterine horns
      were exposed by midline incision with sterile technique and each uterine horn was
      traumatized by bipolar electrocautery. Before closure of the abdomen, 0.9 % NaCl
      solution was administered intraperitoneally in the control group and the gelatin
      thrombin matrix was applied on the traumatized areas on the uterine horns of the
      rats in the study group. At day 21 after the first surgery, the intraperitoneal
      macroscopic adhesion scores and the extent of fibrosis, inflammation scores,
      inflammatory cell activities, inflammation types of adhesion tissues, and the
      level of free oxygen radicals [malondialdehyde (MDA)] and antioxidant enzyme
      activity [superoxide dismutase (SOD) and glutathione S-transferase (GST)] in the
      uterine horn tissue were measured. RESULTS: There was no statistically
      significant difference between the two groups in terms of macroscopic adhesion
      scores (p = 0.064), MDA levels (p = 0.121), and GST activity (p = 0.360).
      However, there was statistically significant difference between the two groups in
      terms of the extent of fibrosis (p < 0.001), inflammation score (p = 0.001),
      inflammatory cell activity (p = 0.002), and SOD activity (p < 0.001).
      CONCLUSIONS: Gelatin-thrombin matrix was found to have increased the extent of
      fibrosis, inflammatory cell activity, and inflammation score, and reduced the
      activity of SOD, which acts to prevent cell damage.

PMID- 24748283
TI  - Collaborative measurement development as a tool in CBPR: measurement development
      and adaptation within the cultures of communities.
AB  - This paper describes the processes we engaged into develop a measurement protocol
      used to assess the outcomes in a community based suicide and alcohol abuse
      prevention project with two Alaska Native communities. While the literature on
      community-based participatory research (CBPR) is substantial regarding the
      importance of collaborations, few studies have reported on this collaboration in
      the process of developing measures to assess CBPR projects. We first tell a story
      of the processes around the standard issues of doing cross-cultural work on
      measurement development related to areas of equivalence. A second story is
      provided that highlights how community differences within the same cultural group
      can affect both the process and content of culturally relevant measurement
      selection, adaptation, and development. 

PMID- 24748284
TI  - Miami thrives: weaving a poverty reduction coalition.
AB  - In an environment where community based organizations are asked to do
      increasingly more to alleviate the effects of complex social problems, networks
      and coalitions are becoming the answer for increasing scale, efficiency,
      coordination, and most importantly, social impact. This paper highlights the
      formation of a poverty reduction coalition in south Florida. Our case study
      approach chronicles a developing coalition in Miami-Dade County and the role of
      one organization acting as lead to the initiative. Drawing on interviews with
      lead organization staff, participant observation field notes, network mapping and
      analysis of documents and artifacts from the initiative, we analyze the local
      organizational context and illuminate important processes associated with
      supporting a developing coalition. Findings offer a picture of the
      interorganizational relationships in the community using social network analysis
      and identify the organizational capacity factors that contribute to and inhibit
      the formation of a cohesive and effective coalition in this context. This study
      also highlights the utility of an action research approach to organizational
      learning about coalition-building in such a way that informs decision making. 

PMID- 24748285
TI  - Atypical hip pain: coexistence of femoroacetabular impingement (FAI) and osteoid
      osteoma.
AB  - The objective of this article was to emphasize the importance of including less
      common causes of hip pain in a differential diagnosis, particularly when clinical
      and radiographic variables are atypical. This article presents the case of a 52
      year-old patient with a history of progressive hip pain resulting from the
      coexistence of both a femoroacetabular impingement (FAI) and an intraarticular
      osteoid osteoma. The intraarticular osteoid osteoma was initially overlooked due
      to its unremarkable features on radiographic and resonance imaging. Consequently,
      the patient was surgically treated for FAI with only partial relief. An
      osteolytic nidus characteristic of osteoid osteoma was discovered only 1.5 years
      following surgery. The patient was subsequently treated for osteoid osteoma with
      anti-inflammatories, after which his pain began to resolve. The patient was
      completely pain free after 7 months. Level of evidence V.

PMID- 24748286
TI  - The effects of repeated intra-articular PRP injections on clinical outcomes of
      early osteoarthritis of the knee.
AB  - PURPOSE: To assess the outcome of intra-articular platelet-rich plasma (PRP)
      injections into the knee in patients with early stages of osteoarthritis (OA) and
      to determine whether cyclical dosing would affect the end result. METHODS: This
      is a prospective, randomized study in which 93 patients (119 knees) were followed
      up for a minimum of 2 years. Fifty knees were randomly selected prior to the
      first injection, to receive a second cycle at the completion of 1 year. A cycle
      consisted of three injections, each given at a monthly interval. The outcome was
      assessed using Knee Injury and Osteoarthritis Outcome Score (KOOS), Visual
      Analogue Scale (VAS), Tegner and Marx scoring systems, recorded prior to the
      first injection and then at 12, 18 and 24 months. RESULTS: There was a
      significant improvement in all scores over time compared to the pre-treatment
      value (p < 0.001). At 12 months, both groups showed similar and significant
      improvement. At 18 months, except for KOOS (Symptoms) and Tegner score, all other
      parameters showed a significant difference between the two groups in favour of
      the patients who had received the second cycle (p < 0.001). At 2 years, the
      scores declined in both groups but remained above the pre-treatment value with no
      significant difference between the groups despite the patients with two cycles
      showing higher mean values for all the scores. CONCLUSION: Intra-articular PRP
      injections into the knee for symptomatic early stages of OA are a valid treatment
      option. There is a significant reduction in pain and improvement in function
      after 12 months, which can be further improved at 18 months by annual repetition
      of the treatment. Although the beneficial effects are ill sustained at 2 years,
      the results are encouraging when compared to the pre-treatment function. LEVEL OF
      EVIDENCE: II.

PMID- 24748288
TI  - How to use fluoride effectively for dental caries prevention?

PMID- 24748287
TI  - Biplanar supracondylar femoral derotation osteotomy for patellofemoral
      malalignment: the anterior closed-wedge technique.
AB  - Patellofemoral malalignment can be caused by several factors including increased
      internal torsion of the femur. As a causative treatment method, supracondylar
      femoral derotation osteotomies have been proposed. For valgus- and varus
      producing supracondylar femoral osteotomies, a biplanar osteotomy has been
      introduced in order to enhance primary fixation stability and osseous
      consolidation by increased bone-to-bone contact. In this article, a modification
      of this technique is described, which allows for a biplanar supracondylar femoral
      derotation osteotomy. LEVEL OF EVIDENCE: V.

PMID- 24748289
TI  - Dental research--looking for funding and beyond.

PMID- 24748290
TI  - Dental bleaching with a 10% hydrogen peroxide product: a six-month clinical
      observation.
AB  - CONTEXT: The possibility of bleaching vital teeth with peroxide-based products
      considerably revolutionized esthetic dentistry. AIM: The aim of this clinical
      study was to evaluate tooth color change and dental sensitivity after exposure to
      preloaded film containing a 10% hydrogen peroxide whitening system (Opalescence
      Trthetaswhite Supreme). MATERIALS AND METHODS: A total of 13 volunteers, aged 18
      to 25 years, participated in this study. The patients used the whitening system
      once a day for 60 minutes during the 8-day study. For maxillary incisors and
      canines, the color change was visually evaluated with the Vita color scale
      before, immediately, and six months after the treatment. Tooth sensitivity was
      evaluated during the daily gel applications. All whitening applications were done
      in office and under the supervision of a dental professional. STATISTICAL
      ANALYSIS USED: The results were analyzed using the Friedman Test (nonparametric
      repeated measures ANOVA) at a level of 5%, and Dunn's Multiple Comparison Test at
      the level of 5%. RESULTS: It was verified that the original mean color values
      observed at the baseline analysis differed significantly from those observed
      immediately after bleaching, as well as from those seen in the analysis at six
      months ( P = 0.001). There was no significant difference between the mean color
      values observed in the immediate time and in the analysis at six months ( P =
      0.474). No tooth sensitivity was observed in any patients. CONCLUSION: It was
      concluded that the bleaching technique using the 10% hydrogen peroxide system was
      effective in a short period of time without tooth sensitivity during
      applications.

PMID- 24748291
TI  - Association between respiratory problems and dental caries in children with
      bruxism.
AB  - CONTEXT: Bruxism is the habit of clenching or grinding one's teeth in non
      functional activities and affects both children and adults alike. Respiratory
      problems, such as asthma and upper airway infections, are reported to be the
      etiological factors of bruxism. AIMS: The aim of the present study was to
      determine whether there is an association between respiratory problems and dental
      caries in children who exhibit the habit of bruxism. SETTING AND DESIGN: An
      observational cross-sectional study was carried out. MATERIALS AND METHODS:
      Patient histories were taken and clinical exams were performed on 90 children for
      selection and allocation to one of two groups. For the determination of bruxism,
      a questionnaire was administered to parents/guardians and an oral clinical exam
      was performed based on the criteria of the American Academy of Sleep Medicine.
      Thirty-three male and female children between 4 and 7 years of age participated
      in the study - 14 children with bruxism and 19 children without bruxism.
      STATISTICAL ANALYSIS: The data were statistically analyzed using the chi-square
      test, with level of significance set at 5% (P < 0.05). RESULTS: Mean age of the
      participants was 5.73 years. The male gender accounted for 45.5% (n = 15) of the
      sample and the female gender accounted for 54.5% (n = 18). A statistically
      significant association was found between respiratory problems and dental caries
      among the children with bruxism. Seventy-seven percent of the children with
      bruxism had caries and 62.5% the children with respiratory problems exhibited the
      habit of bruxism. CONCLUSIONS: There seems to be an association between bruxism,
      respiratory problems, and dental caries in children.

PMID- 24748292
TI  - Characterization of stem cells from the pulp of unerupted third molar tooth.
AB  - CONTEXT: Dental pulp stem cells (DPSCs) are the most diagnosed type of stem cells
      isolated from dental tissues. Previous studies demonstrate that tissues in
      earlier stages of development could be better stem cell resources for tissue
      engineering. AIMS: In this study, aiming at finding younger stem cell resources,
      we chose the pulp of human unerupted third molar teeth when the crown was
      completely formed and the roots had not begun their development, Nolla's 6 th
      developmental stage (N6 th ). MATERIALS AND METHODS: Surgical removal of the
      third molar was performed by aseptic technique with minimal trauma. The tissues
      were digested enzymatically and the resulted single cells were cultured.
      Immunophenotypic characterization of the cells was done via immunocytochemistry,
      immunofluorescence, and flow cytometry assays. Adipogenic and osteogenic
      differentiation potential of these cells was examined and confirmed by
      histochemical staining and reverse transcription-polymerase chain reaction
      analysis. STATISTICAL ANALYSIS USED: This study is descriptive. RESULTS: N6 th 
      unerupted dental pulp cultured cells expressed DPSC markers: Vimentin, CD73,
      CD90, CD105, CD166, CD44, CD146, and STRO-1, but did not express hematopoietic
      cell markers: CD14, CD34, CD45, HLA-DR and were also negative for dentin
      sialoprotein negative showing an undifferentiated preodontogenic state.
      Adipocytes differentiated from N6 th -DPSCs were positively stained with Oil-Red
      O and expressed both early and late adipocyte specific genes. Formation of
      Alizarin-red positive condensed calcium-phosphate nodules accompanied by strong
      expression of two osteogenic mRNAs, exhibited osteogenic differentiation.
      CONCLUSION: Based on the results of this study, we suggest that N6 th -DMSCs are
      a viable choice for cryo-banking and future usage in regenerative therapies;
      however, more investigations are necessary before clinical application can
      commence.

PMID- 24748293
TI  - Periapical tissue reaction to calcium phosphate root canal sealer in porcine
      model.
AB  - BACKGROUND: Calcium phosphate cements (CPC) are a group of biomaterials
      possessing wide scope of use in various branches of medical science. These
      materials have been proposed to be highly biocompatible and osteoconductive. This
      study is based on a newly developed CPC formulation (Chitra-CPC) and is aimed at
      the evaluation of its biocompatibility through an Endodontic Usage Test in a
      porcine study model. OBJECTIVE: To evaluate the periapical tissue reaction to
      Chitra-CPC when used as a root canal sealer/filler material in comparison with a
      resin sealer, AH Plus (Dentsply). MATERIALS AND METHODS: The procedure was done
      on porcine animal model following the ISO 7405 criteria. The material was
      implanted intentionally into the periapical area of 36 teeth through a root canal
      procedure carried out in six animals which were divided equally among 1-month and
      3-month time periods. Results were based on the histological evaluation of the
      autopsied specimens after the prescribed time periods. RESULTS: Mild to moderate
      periapical tissue reaction was found in Chitra-CPC samples belonging to the 1
      month time period, whereas majority of the 3-month CPC samples showed an absence
      of inflammation. Samples of AH Plus in 1-month period showed severe to moderate
      inflammation, whereas 3-month AH Plus samples had a mild to moderate
      inflammation. CONCLUSIONS: Chitra-CPC is a biocompatible material.

PMID- 24748294
TI  - Degree of chronic orofacial pain associated to the practice of musical
      instruments in orchestra's participants.
AB  - OBJECTIVE: The practice of playing musical instruments can affect structures of
      the head, neck, mouth, and the masticatory system. The aim of this study was to
      obtain information regarding the prevalence of orofacial pain in musicians
      according to the type of instrument they play, by applying a specific
      questionnaire. MATERIALS AND METHODS: One hundred and seventeen musicians of Sao
      Paulo state's orchestras participated in this study. They answered an anamnesis
      questionnaire with 20 questions regarding their personal data, type of instrument
      played, hours of daily practice, and presence or absence of orofacial pain
      according to the Chronic Pain Grade Classification (CPGC). Musicians were divided
      into two groups in accordance with the risk of affecting TMJ: RG (risk group,
      including violin, viola, vocalist, trombone, tuba, clarinet and saxophone); CG
      (control group, other instruments). They received an informative brochure about
      the subject. Data obtained from the questionnaire were submitted to descriptive
      statistics, Pearson's correlation analysis and Z-test for difference between two
      proportions. RESULTS: The participants were from 15 to 62 years old. Pain degree
      showed positive correlation for reported symptoms (P = 0.002) and hour/day
      practice (P = 0.030). Regarding the prevalence of pain degree, data were, for RG:
      Grade 0 (54.5%), Grade 1 (30.3%), and Grade >=2 (15.1%). For CG, Grade 0 (84.4%),
      Grade 1 (8.9%), and Grade >=2 (6.6%). Z-test showed positive difference between
      groups (P = 0.0001). CONCLUSION: It was concluded that the musicians of risk
      group presented higher prevalence of orofacial pain than control (non-risk)
      group.

PMID- 24748295
TI  - Analysis of the surface deformation of dental implants submitted to pullout and
      insertion test.
AB  - OBJECTIVE: The aim of the present study was to evaluate the possible deformations
      in the surface of dental implants submitted to pullout and insertion test in
      polyurethane synthetic bone, using scanning electron microscopy. MATERIAL AND
      METHODS: Four different types of implants were used: Master Screw, Master Porous,
      Master Conect AR and Master Conect Conical (n = 8). These implants were into the
      femoral head synthetic bone (Synbone) and removed through the pullout test,
      performed with a universal testing machine (EMIC MEM 2000). All the screws,
      before and after the mechanical tests, were micro structurally analyzed in a
      Scanning Electron Microscope (SEM - Zeiss EVO50), utilizing a magnification of 35
      times. The results were subjected to ANOVA and Tukey tests (alpha =0.05).
      RESULTS: Only the Master Conect Conical and Master Porous implants presented
      statistically significant difference to pullout and maximum deformation (P =
      0.014 and P = 0.009, respectively). The SEM images did not show morphological
      changes of the implants when compared before and after the mechanical tests.
      CONCLUSION: We concluded that Master Porous presented higher pullout resistance,
      suggesting a greater primary stability.

PMID- 24748296
TI  - Reliability of digital panoramic radiographs in detecting calcified carotid
      artery atheromatous plaques: a clinical study.
AB  - OBJECTIVES: The objective of this study was to determine whether digital
      panoramic radiography is a reliable method to detect calcified carotid artery
      atheromatous plaques (CCAAP) as compared with ultrasonography. STUDY DESIGN:
      Digital panoramic radiographs were obtained from 50 patients who also underwent
      carotid ultrasound examination. The images were interpreted by trained
      maxillofacial radiologist for the presence or absence of calcified atheromatous
      plaques. The extent of carotid calcification on carotid ultrasonography was
      determined by a trained Sonologist, which was considered as the gold standard
      assessment. RESULTS: Digital panoramic radiographs had a sensitivity of 76% and
      specificity of 98.66% in determining CCAAP. There was a high level of agreement
      between diagnoses, with a kappa value of 0.8. CONCLUSION: To conclude, digital
      panoramic radiographs had good sensitivity and high specificity in detecting
      CCAAP. If properly trained, dentists can detect such plaques and can refer
      patients to physician for timely medical treatment.

PMID- 24748297
TI  - Analysis of serum and salivary immunoglobulin M in patients with orofacial
      epithelial cancers.
AB  - CONTEXT: The physiological changes in the humoral immune system of patients with
      orofacial epithelial cancers (OECs) are considered key factors in the
      pathogenesis, prognosis, and management of these individuals. AIM: This study
      assessed the serum and salivary immunoglobulin M (IgM) levels in patients with
      OECs. SETTINGS AND DESIGNS: This is a cross-sectional study of the serum and
      salivary IgM profile among patients with OEC and healthy controls. MATERIALS AND
      METHODS: There were 78 subjects comprising 30 patients with untreated OEC, 18
      patients with OEC receiving treatment and 30 healthy, age and gender matched
      individuals. The serum and salivary samples from the participants were analyzed
      for IgM using the enzyme linked immunosorbent assay technique. RESULTS: The mean
      value of serum IgM in OEC patients receiving treatment was significantly lower
      compared to untreated OEC patients and healthy controls (P = 0.01). However, the
      mean serum IgM among untreated OEC patients was not significantly different
      compared with healthy controls. In contrast, the salivary IgM level did not show
      any significant difference among the three groups (P = 0.06). Furthermore, there
      was no correlation between the serum and salivary levels of IgM among the
      subjects. CONCLUSION: The findings from this study suggest that serum IgM levels
      in OEC patients receiving treatment might be good biomarker while salivary IgM
      may not be reliable as a marker in these individuals.

PMID- 24748298
TI  - MSX 1 gene variant and non-syndromic clefting: association or rejection?
AB  - CONTEXT: Non-syndromic cleft lip/palate (NSCL/P) is a congenital anomaly with
      significant medical, psychological and social ramifications. There is sufficient
      evidence to hypothesize that locus for this condition can be identified by
      candidate genes. AIMS: The aim of this study is to amplify the chosen region (799
      G >T) of MSX 1 gene, investigate the degree of association and perform a mutation
      research from Raichur cleft lip and palate patient sample. SETTINGS AND DESIGN:
      Case history and clinical examination of the patient were recorded to rule.
      Written consent was obtained from patients and controls for in vivo study. STUDY
      WAS DESIGNED IN FOUR STEPS AS FOLLOWS: a. Collection of a blood sample; b.
      Genomic deoxyribonucleic acid (DNA) extraction; c. Polymerase chain reaction
      (PCR); d. Restriction fragment length polymorphism (RFLP). MATERIALS AND METHODS:
      Blood samples were collected from 50 subjects having NSCL/P and 50 controls.
      Genomic DNA was extracted, PCR and RFLP was performed for digestion products that
      were evaluated. STATISTICAL ANALYSIS: Chi-square test with P value at 95%
      confidence intervals. RESULTS: The results showed a positive correlation between
      MSX 1 799 G >T gene variant and NSCL/P patients in Raichur patients. CONCLUSIONS:
      From a genetically diverse etiology MSX 1 799 G >T gene variant may be a good
      screening marker for NSCL/P in Raichur patients.

PMID- 24748299
TI  - Periodontal status in infertile women attending in vitro fertilization clinics.
AB  - BACKGROUND AND AIM: Throughout a woman's life, hormonal influences affect
      therapeutic decision making in periodontics. A woman undergoing infertility
      treatment is given drugs to stimulate the ovaries, which lead to sustained higher
      levels of female sex hormones. The differing levels of these hormones, either in
      infertile women or in women undergoing therapy for infertility or in women who
      have conceived and delivered naturally could suggest a differing periodontal
      status amongst these three groups. Hence, this cross-sectional study was
      undertaken to assess and compare the periodontal status in the above three
      groups. MATERIALS AND METHODS: 180 women including 60 women undergoing treatment
      for infertility (Group I), 60 women in whom infertility treatment had not yet
      been initiated (Group II) and 60 women who had conceived and delivered naturally
      (Group III-control group), of age range 25-35 years, were included. Clinical
      parameters including oral hygiene index simplified (OHI-S), gingival index,
      sulcus bleeding index (SBI) and clinical attachment loss (CAL) were assessed by a
      single examiner. RESULTS: Despite similar OHI-S scores (P > 0.05) in all groups,
      women of Group I had significantly higher gingival inflammation and SBI (P <
      0.05) as compared to women of Group II and Group III. Furthermore, the women in
      Group I and Group II had statistically higher CAL (P < 0.05) as compared with the
      control group. CONCLUSION: Within the limits of this study, it can be concluded
      that altered hormonal levels in infertile women undergoing assisted reproductive
      therapy and infertile women not undergoing this treatment can lead to increased
      attachment loss, suggesting that these women may require constant periodontal
      monitoring.

PMID- 24748300
TI  - Ultrasound imaging versus conventional histopathology in diagnosis of periapical
      lesions of endodontic origin: a comparative evaluation.
AB  - CONTEXT: Accurate assessment of periapical status is critical in diagnosis,
      treatment planning, and evaluation of healing. Novel imaging modalities like
      sonography offer promising results with reduced radiation risks. AIMS: To
      evaluate the potential of ultrasound imaging technique together with the
      application of color Doppler to differentiate between periapical lesions of
      endodontic origin. MATERIALS AND METHODS: Twenty patients with periapical lesions
      of endodontic origin who were already scheduled for undergoing endodontic surgery
      were examined further using sonography. Color Doppler was performed to assess
      blood flow. Information on the size of the lesion, its content, and vascular
      supply was gained and recorded by means of ultrasound images. The sonographic
      images were analyzed and discussed with an expert sonologist, and a tentative
      diagnosis between a periapical cyst and periapical granuloma was made. Endodontic
      surgery and histopathological examination was done for each case and the results
      were compared. RESULTS: The sonograms revealed the lesions within the bone in
      three dimensions and their contents, that is, fluids or tissues or blood vessels.
      Measurements of the periapical lesions in three dimensions were also obtained. Of
      the twenty cases studied, ultrasound could detect periapical granulomas in all 9
      cases and radicular cysts in all 11 cases. CONCLUSION: Ultrasound imaging had the
      potential to be used for the evaluation of periapical lesions of endodontic
      origin. However, further studies are required to establish a definite
      correlation.

PMID- 24748301
TI  - Randomized clinical study comparing metallic and glass fiber post in restoration
      of endodontically treated teeth.
AB  - BACKGROUND: Post-retained crowns are indicated for endodontically treated teeth
      (ETT) with severely damaged coronal tissue. Metallic custom and prefabricated
      posts have been used over the years, however, due to unacceptable color, extreme
      rigidity and corrosion, fiber posts, which are flexible, aesthetically pleasing
      and have modulus of elasticity comparable with dentin were introduced. AIM: To
      compare clinical performance of metallic and glass fiber posts in restoration of
      ETT. MATERIALS AND METHODS: 40 ETT requiring post retained restorations were
      included. These teeth were randomly allocated into 2 groups. Twenty teeth were
      restored using a glass fiber-reinforced post (FRP) and 20 others received
      stainless steel parapost (PP), each in combination with composite core buildups.
      Patients were observed at 1 and 6 months after post placement and cementation of
      porcelain fused to metal (PFM) crown. Marginal gap consideration, post retention,
      post fracture, root fracture, crown fracture, crown decementation and loss of
      restoration were part of the data recorded. All teeth were assessed clinically
      and radiographically. Fisher's exact test was used for categorical values while
      log-rank test was used for descriptive statistical analysis. RESULTS: One tooth
      in the PP group failed, secondary to decementation of the PFM crown giving a 2.5%
      overall failure while none in the FRP group failed. The survival rate of FRP was
      thus 100% while it was 97.5% in the PP group. This however was not statistically
      significant (log-rank test, P = 0.32). CONCLUSION: Glass FRPs performed better
      than the metallic post based on short-term clinical performance.

PMID- 24748302
TI  - In vitro assessment of antimicrobial activity of Pothomorphe umbellata extracts
      against Enterococcus faecalis.
AB  - BACKGROUND: Due to the complex anatomy of the root canal system, biomechanical
      preparation is not able to completely eliminate all microorganisms present in the
      endodontic infections, making it necessary the use of an intracanal medication.
      AIM: The aim of this study was to assess the antimicrobial activity of an
      intracanal medication containing the ethyl-acetate fraction of Pothomorphe
      umbellata against Enterococcus faecalis. MATERIALS AND METHODS: Fifty seven human
      maxillary canine teeth were used, of which 54 were infected with E. faecalis
      every 72 h, for 28 days, and cultured for 24 h. Contaminated teeth were randomly
      separated into three groups (n = 18) and treated as follows: Group I - calcium
      hydroxide-based medication; Group II - P. umbellata-based medication; Group III -
      contaminated teeth without medication. Three teeth were used as negative control.
      After 7, 14 and 28 days of treatment, six teeth from each group were assessed for
      the level of microbial growth after each period of treatment. RESULTS: The
      intracanal medication containing P. umbellata was effective against E. faecalis
      after 7, 14, and 28 days of treatment without statistically significant
      difference in comparison to calcium hydroxide treatment (Kruskal-Wallis test, P >
      0.05). CONCLUSION: Ethyl-acetate fraction of P. umbellate was efficient against
      E. faecalis, making this phytotherapy a viable option for endodontic treatment.

PMID- 24748303
TI  - In vitro evaluation of two methods of ultrasonic irrigation on marginal
      adaptation of MTA plugs in open apex teeth: a SEM analysis.
AB  - CONTEXT: Different factors can affect the marginal adaptation of MTA. AIMS: The
      present study was designed to investigate the effect of two ultrasonic irrigation
      methods on the marginal adaptation of MTA plug in open apex teeth by scanning
      electron microscope. SETTINGS AND DESIGN: Thirty single mature teeth were
      included in this in vitro experimental prospective study. MATERIALS AND METHODS:
      A total of 5 mm thickness of MTA plug was inserted at the end of the canals and
      after 24 h an ultrasonic file was used to irrigate the canals and remove the MTA
      remnants. Teeth were randomly divided into three groups: In the first and second
      groups, the canals were irrigated for 1 min by 2.5% sodium hypochlorite as #25
      ultrasonic file was in direct contact and 1 mm away from MTA plug, respectively.
      The third group was not irrigated and left as control. A total of 1 mm transverse
      sections were prepared through the coronal and the apical parts of MTA plug and
      specimens were prepared for SEM analysis. The extent of gap was measured linearly
      under SEM device. STATISTICAL ANALYSIS USED: Statistical analysis of the results
      was performed using the kruskal-Wallis test by SPSS software ver.18(a = 0.05).
      RESULTS: There was no significant difference between groups regarding the
      marginal gap size in apical (P: 0.17) and coronal sections (P: 0.33). However,
      the mean marginal gap size was higher in apical section compared to coronal
      section. CONCLUSIONS: It can be concluded that ultrasonic irrigation dose not
      adversely affect the marginal adaptation of MTA plugs.

PMID- 24748304
TI  - A comparative evaluation of compressive strength of Portland cement with zinc
      oxide eugenol and Polymer-reinforced cement: an in vitro analysis.
AB  - OBJECTIVE: The purpose of this study is to evaluate the ultimate compressive
      strength of 50% and 25% Portland cement mixed with Polymer-reinforced zinc oxide
      eugenol and zinc oxide eugenol cement after 1 hour, 24 hours, and 7 days.
      MATERIALS AND METHODS: One hundred and eighty samples were selected. The samples
      were made cylindrical of size 6 * 8 mm and were divided into six groups as
      follows with each group consisting of 10 samples. Group 1: Polymer-reinforced
      zinc oxide eugenol with 50% Portland cement (PMZNPC 50%) Group 2: Polymer
      reinforced zinc oxide eugenol with 25% Portland cement (PMZNPC 25%) Group 3:
      Polymer-reinforced zinc oxide eugenol with 0% Portland cement (PMZNPC 0%) Group
      4: Zinc oxide eugenol with 50% Portland cement (ZNPC 50%) Group 5: Zinc oxide
      eugenol with 25% Portland cement (ZNPC 25%) Group 6: Zinc oxide eugenol with 0%
      Portland cement (ZNPC 0%) These samples were further subdivided based on time
      interval and were tested at 1 hour, 24 hours and at 7 th day. After each period
      of time all the specimens were tested by vertical CVR loaded frame with capacity
      of 5 tones/0473-10kan National Physical laboratory, New Delhi and the results
      were statistically analyzed using ANOVA and Scheffe test. RESULTS: Polymer
      reinforced cement with 50% Portland cement, Zinc oxide with 50% Portland cement,
      Polymer-reinforced cement with 25% Portland cement and Zinc oxide with 25%
      Portland cement exhibited higher compressive strength when compared to Zinc oxide
      with 0% Portland cement and Polymer-reinforced cement with 0% Portland cement, at
      different periods of time. The difference between these two groups were
      statistically significant (P < 0.05) and it is suggested that mixture of 50% and
      25% Portland cement in Zinc oxide eugenol and Polymer-modified zinc oxide cement
      can be used as core build up material and permanent filling material. CONCLUSION:
      It is concluded that 50% and 25% Portland cement in zinc oxide eugenol and
      polymer-modified zinc oxide eugenol results in higher compressive strength and
      hence can be used as permanent filling material and core built-up material.

PMID- 24748305
TI  - Diode lasers: a magical wand to an orthodontic practice.
AB  - LASER (Light Amplification by Stimulated Emission of Radiation) is a powerful
      source of light, which has innumerable applications in all the fields of science
      including medicine and dentistry. It is one such technology that has become a
      desirable and an inseparable alternative to many traditional surgical procedures
      being held in the field of dentistry, and orthodontics is no exception. The
      current article describes the uses of a diode laser as an indispensable tool in
      an orthodontic office. 

PMID- 24748306
TI  - Radiosensitizers, radioprotectors, and radiation mitigators.
AB  - Radiotherapy is regarded as one of the most important therapeutic modality for
      the treatment of malignant lesions. This field is undergoing rapid advancements
      in the recent times. With the use of radiosensitizers and radioprotective agents,
      the course of radiotherapy has improved the sensitization of tumor cells and
      protection of normal cells, respectively. The aim of this paper was to critically
      review and analyze the available compounds used as radiosensitizers,
      radioprotectors, and radiation mitigators. For reviewing, the author used the
      electronic search for the keywords 'Radiosensitizers', 'Radioprotectors',
      'Radiation mitigators' on PubMed for inclusion of previously published articles
      and further search of reference papers on individual radiosensitizing and
      radioprotecting agents was done. Radiosensitizers are agents that sensitize the
      tumor cells to radiation. These compounds apparently promote fixation of the free
      radicals produced by radiation damage at the molecular level. The mechanism of
      action is similar to the oxygen effect, in which biochemical reactions in the
      damaged molecules prevent repair of the cellular radiation damage. Free radicals
      such as OH + are captured by the electron affinity of the radiosensitizers,
      rendering the molecules incapable of repair. Radioprotectors are compounds that
      are designed to reduce the damage in normal tissues caused by radiation. These
      compounds are often antioxidants and must be present before or at the time of
      radiation for effectiveness. Other agents, termed mitigators, may be used to
      minimize toxicity even after radiation has been delivered. This article tries to
      discuss the various aspects of radiosensitizers, radioprotectors, and radiation
      mitigators including the newer agents. 

PMID- 24748307
TI  - Procedures to view aberrations--a travel from protein to gene: literature review.
AB  - The diagnosis of any pathology is fundamentally based on the microscopic
      structure of cells and tissues and this remains as the standard by which all
      other diagnostic tests are measured. In this era, the pathologists are relying on
      the examination of tissue section stained by histochemical means and it is
      supported by the advanced immunological, biochemical and molecular techniques.
      This review will provide the information about one of the way that can be
      followed to unravel the molecular mechanism in spotting the disease process.
      Technologies used to study the cellular process are same for the normal and the
      abnormal cell. Experimental strategy briefed here is also applicable for both.
      The cellular process can be studied either from protein to gene or from gene to
      protein. Earlier days biochemical analysis (isolation of protein, protein
      sequencing) was separate and genetic analysis (genomic mapping) was separate. But
      now with advent of recombinant DNA technology it is possible to have a link
      between the biochemical and genetic analysis. Intermediary step of development of
      oligonucleotide synthesis, complementary DNA probe and cloning has revolutionized
      the research process. Identified gene can be compared with the normal gene by
      comparative genomics or expressed proteins by expression proteomics. 

PMID- 24748308
TI  - A novel approach in treating horizontally fractured canine using RIBBOND splint
      and MTA as an obturating material and intra-radicular splint: a case report.
AB  - Radicular fractures in permanent teeth are uncommon injuries among dental
      traumas, being only 0.5-7% of the cases. Management of horizontal root fractures
      presents a formidable challenge for clinicians because of the difficulty of
      achieving a stable reunion of fracture fragments. This case report presents the
      management of horizontally fractured canine by approximation of fracture
      fragments, fiber splinting, and use of MTA - both as an obturating material and
      intra-radicular splint. Short-term follow-up of the case showed promising results
      both clinically and radiographically. 

PMID- 24748309
TI  - Cone beam computed tomography: a tool for the diagnosis of confusing periapical
      lesions in conventional radiographs.
AB  - We report two cases in which cone beam computed tomography (CBCT) was essential
      for the establishment of the diagnosis of periapical lesions. CBCT allows a three
      dimensional assessment of a specific region with no superimposition of
      structures. Therefore, its use is recommended when radiographic images are not
      sufficient for the diagnosis. 

PMID- 24748310
TI  - Unilateral segmental odontomaxillary dysplasia: a rare entity of 3 cases and
      review.
AB  - Segmental odontomaxillary dysplasia (SOD) is an uncommon, nonhereditary, rare
      developmental disorder primarily involving the posterior part of the maxilla and
      related dental components. It is a rare condition of uncertain etiology that
      results in painless unilateral expansion of the posterior dentoalveolar complex,
      gingival hyperplasia, lack of one or both premolars in the affected area, delayed
      eruption of adjacent teeth and malformations of the primary molars.
      Radiographically, the affected bone is thickened and irregular in outline, with a
      coarse trabecular pattern that is vertically oriented resulting in a relatively
      radioopaque granular appearance. The treatment is focused on extraction of the
      involved teeth, while in some milder cases the teeth may be retained for a long
      period. The treatment plan should be based on the degree of involvement as well
      as the functional and esthetic needs in each case. Considering the rarity of the
      condition, we report three cases of SOD with variable presentations in a 45-year
      old, 24-year-old and 23-year-old individual. 

PMID- 24748311
TI  - A novel technique for removal of broken instrument from root canal in mandibular
      second molar.
AB  - The fracture of an endodontic instrument is an obstacle in completion of a
      routine successful pulp space therapy. Ni-Ti instruments corrode when in contact
      with sodium hypochlorite which leads to their deterioration and ultimately
      fracture during use. Removal of separated instrument from root canal is often a
      very difficult procedure. This procedure is more complicated when the instrument
      separated is closer to the mandibular canal. A case is presented in which a
      separated hand instrument was retrieved from the mesio buccal of a second molar
      approximating the mandibular canal root by replantation. 

PMID- 24748312
TI  - A 'pen' in the neck: an unusual foreign body and an unusual path of entry.
AB  - Penetrating injuries to head and neck region with varying objects have been
      reported in the literature. Majority of these injuries occur in interpersonal
      violence or bomb blasts or road traffic accidents. Despite the improvement in
      imaging technologies and surgical methods, penetrating injuries to head and neck
      with impacted foreign bodies are very challenging due to the proximity to vital
      structures and/or difficulties in accessing them for the removal. Following
      injury the normal anatomy could be altered because of edema or tissue
      destruction, which makes the diagnosis or retrieval more difficult.
      Parapharyngeal or prevertebral space is an unusual place for lodgment of foreign
      bodies and in these cases the usual point of entry is the oral cavity, cheek or
      neck. Here, we report a case of a ball point pen extending to the prevertebral
      region at the level of C1-C2 vertebrae from point of entry at the suprazygomatic
      region in the temporal fossa.

PMID- 24748313
TI  - Benign fibrous histiocytoma of the maxilla: a case report and review of
      literature.
AB  - Benign fibrous histiocytoma (BFH) is a mesenchymal tumor which commonly affects
      the skin of extremities. Histologically, BFH of soft tissues and bone shows
      similar features, but BFH of the bone is rare with less than 100 cases reported
      worldwide and usually it involves tibia, femur, and pelvic bone. As far as the
      oral cavity is concerned, majority of the BFHs are found in the soft tissues of
      the buccal mucosa, gingiva, lower and upper lips, soft palate, and floor of the
      mouth. Occurrence of this tumor in the jaw bones is extremely rare as only one
      case of the maxilla and six cases of the mandible have been reported so far .
      Hence, the purpose of this article is to report the second case of BFH of the
      maxilla in a 23-year-old female patient and to review the literature of this
      entity affecting the jaws. 

PMID- 24748314
TI  - The coexistence of paroxysmal hemicrania and temporomandibular disorder:
      importance of multidisciplinary approach.
AB  - Paroxysmal hemicrania (PH) is a trigeminal autonomic cephalalgia, a rare primary
      headache characterized by unilateral periorbital and/or temporal attacks of
      severe intensity and short duration. In this situation, the determination of a
      correct diagnosis is crucial for the establishment of a proper management
      strategy. In the case of head and facial pain, this step is usually a big
      challenge since many conditions share the same features, as some primary
      headaches and temporomandibular disorders (TMD). The relationship between PH and
      TMD has not been determined. This paper describes a case of a female patient
      diagnosed with TMD and presenting concomitant headache attacks fulfilling the
      International Headache Society's criteria for PH. It is also emphasized the
      importance of dentist in this scenario, for many times responsible for the
      initial diagnosis of facial/head pain. Moreover, it is presented an integrated
      and simultaneously approach of both conditions, PH and TMD. 

PMID- 24748315
TI  - Pleomorphic adenoma of cheek: a rare case report and review of literature.
AB  - Pleomorphic adenoma (PA) is the most common tumor of the salivary glands. About
      90% of these tumors occur in the parotid gland and 10% in the minor salivary
      glands. The most common sites of PA of the minor salivary glands are the palate,
      followed by lips and cheeks. Throat, floor of the mouth, tongue, tonsil, pharynx,
      retromolar area and nasal cavity are rarely involved. Here, we report a case of
      PA of the cheek in a 42-year-old female. The mass was excised and the patient was
      followed for 3 years post operatively with no recurrence. 

PMID- 24748316
TI  - Four impacted canines in an adult patient: a challenge in orthodontics.
AB  - This case report illustrates the management of four impacted canines in an adult
      patient associated with prolonged retention of the four deciduous teeth. The
      treatment plan was formulated to extract the lower deciduous teeth, application
      of the forced eruption with the permanent canines, and extract the upper
      permanent canines and maintenance of the maxillary deciduous canines. No
      reshaping of the maxillary deciduous teeth was performed because the patient was
      satisfied with the results. 

PMID- 24748317
TI  - Modern trends in modeling of extra-oral defects.
AB  - Maxillofacial prostheses are usually fabricated on the basis of conventional
      impressions and techniques. The extent to which the prosthesis reproduces normal
      facial morphology depends on the clinical judgment and skill of the individual
      fabricating the prosthesis. Recently, as a result of advances in technology,
      various computer-aided design and manufacturing techniques have been successfully
      introduced for the automated fabrication of maxillofacial prostheses. These
      systems are able to provide more consistently accurate reproduction of facial
      morphology. 

PMID- 24748318
TI  - Indian scenario: genetic polymorphisms in periodontal diseases.

PMID- 24748319
TI  - ALPPS offers a better chance of complete resection in patients with primarily
      unresectable liver tumors compared with conventional-staged hepatectomies:
      results of a multicenter analysis.
AB  - BACKGROUND: Portal vein occlusion to increase the size of the future liver
      remnant (FLR) is well established, using portal vein ligation (PVL) or
      embolization (PVE) followed by resection 4-8 weeks later. Associating liver
      partition with portal vein ligation for staged hepatectomy (ALPPS) combines PVL
      and complete parenchymal transection, followed by hepatectomy within 1-2 weeks.
      ALPPS has been recently introduced but remains controversial. We compare the
      ability of ALPPS versus PVE or PVL for complete tumor resection. METHODS: A
      retrospective review of all patients undergoing ALPPS or conventional staged
      hepatectomies using PVL or PVE at four high-volume HPB centres between 2003 and
      2012 was performed. Patients with primary liver tumors and liver metastases were
      included. Primary endpoint was complete tumor resection. Secondary endpoints
      include 90-day mortality, complications, FLR increase, time to resection, and
      tumor recurrence. RESULTS: Forty-eight patients with ALPPS were compared with 83
      patients with conventional-staged hepatectomies. Eighty-three percent (40/48
      patients) of ALPPS patients achieved complete resection compared with 66 % (55/83
      patients) in PVE/PVL (odds ratio 3.34, p = 0.027). Ninety-day mortality in ALPPS
      and PVE/PVL was 15 and 6 %, respectively (p = 0.2). Extrapolated growth rate was
      11 times higher in ALPPS (34.8 cc/day; interquartile range (IQR) 26-49) compared
      with PVE/PVL (3 cc/day; IQR2-6; p = 0.001). Tumor recurrence at 1 year was 54
      versus 52 % for ALPPS and PVE/PVL, respectively (p = 0.7). CONCLUSIONS: This
      study provides evidence that ALPPS offers a better chance of complete resection
      in patients with primarily unresectable liver tumors at the cost of a high
      mortality. The technique is promising but should currently not be used outside of
      studies and registries.

PMID- 24748320
TI  - Unplanned extubation and mortality in surgical critically patients: an accidental
      association or cause?

PMID- 24748321
TI  - Can virtual non-enhanced CT be used to replace true non-enhanced CT for the
      detection of palpable cervical lymph nodes? A preliminary study.
AB  - PURPOSE: To investigate the potential of virtual non-contrast CT (VNCT) from dual
      energy CT to replace true nonenhanced CT (TNCT) for the detection of enlarged
      cervical lymph nodes. MATERIALS AND METHODS: Thirty-nine patients with 94
      histopathologically proven cervical lymph nodes were imaged with the dual-energy
      CT technique. VNCT images from the arterial [VNCT-A] and venous phases [VNCT-V]
      were obtained with the liver VNC application. The mean CT number and signal-to
      noise ratio (SNR) were compared. Image quality was evaluated with a score scale
      of 1-5. Effective dose (ED) was calculated and compared. RESULTS: Mean CT numbers
      of cervical lymph nodes were higher on VNCT than on TNCT (P = 0.034). There was
      no difference in the SNR among three sets of non-enhanced CT images, but the CNR
      of VNCT images was higher than that of TNCT images (P < 0.001). Image quality of
      VNCT from two phases was comparable to that of TNCT (P = 0.070). There was no
      difference in image quality of three sets of non-enhanced CT images (P > 0.05).
      ED from dual-phase dual-energy CT was lower than that from tri-phase CT scans (P
      < 0.001). CONCLUSION: VNCT images from dual-energy CT of the neck had diagnostic
      image quality; they have the potential to replace TNCT, thus reducing the
      radiation dose.

PMID- 24748322
TI  - Microenvironmentally controlled secondary structure motifs of apolipoprotein A-I
      derived peptides.
AB  - The structure of apolipoprotein A-I (apoA-I), the major protein of HDL, has been
      extensively studied in past years. Nevertheless, its corresponding three
      dimensional structure has been difficult to obtain due to the frequent
      conformational changes observed depending on the microenvironment. Although the
      function of each helical segment of this protein remains unclear, it has been
      observed that the apoA-I amino (N) and carboxy-end (C) domains are directly
      involved in receptor-recognition, processes that determine the diameter for HDL
      particles. In addition, it has been observed that the high structural plasticity
      of these segments might be related to several amyloidogenic processes. In this
      work, we studied a series of peptides derived from the N- and C-terminal domains
      representing the most hydrophobic segments of apoA-I. Measurements carried out
      using circular dichroism in all tested peptides evidenced that the lipid
      environment promotes the formation of alpha-helical structures, whereas an
      aqueous environment facilitates a strong tendency to adopt beta-sheet/disordered
      conformations. Electron microscopy observations showed the formation of amyloid
      like structures similar to those found in other well-defined amyloidogenic
      proteins. Interestingly, when the apoA-I peptides were incubated under conditions
      that promote stable globular structures, two of the peptides studied were
      cytotoxic to microglia and mouse macrophage cells. Our findings provide an
      insight into the physicochemical properties of key segments contained in apoA-I
      which may be implicated in disorder-to-order transitions that in turn maintain
      the delicate equilibrium between both, native and abnormal conformations, and
      therefore control its propensity to become involved in pathological processes. 

PMID- 24748323
TI  - Enhanced proliferation of bone marrow mesenchymal stem cells by co-culture with
      TM4 mouse Sertoli cells: involvement of the EGF/PI3K/AKT pathway.
AB  - Bone marrow mesenchymal stem cells (BM-MSCs) are considered as a promising option
      in the field of regenerative medicine and tissue engineering. However, little is
      known about how TM4 mouse Sertoli cells, which are known to enhance stem cells
      proliferation in co-culture, may influence the proliferation of BM-MSCs and which
      signaling pathways are involved in. To address these questions, an in vitro
      transwell system was used. We found that TM4 cells could produce soluble factors
      which enhanced the growth of BM-MSCs without inhibiting the multipotency.
      Furthermore, cell cycle analysis showed that co-culture with the TM4 cells
      accelerated the progress of BM-MSCs from the G1 to the S phase. The expression of
      the phospho-akt, mdm2, as well as pho-CDC2, and cyclin D1 were markedly
      upregulated in co-cultured BM-MSCs. The observed promoting effect was
      significantly inhibited by the administration of the PI3K/AKT inhibitor,
      LY294002. Among the various growth factors produced by TM4 cells, the epithelial
      growth factor (EGF) stimulated the proliferation of the BM-MSCs more
      significantly compared with the other growth factors examined in this study.
      Neutralization of EGF via a blocking antibody significantly limited the promoting
      growth effect in BM-MSCs. These results suggest that TM4 cells provide a
      favorable in vitro environment for BM-MSCs growth and imply the involvement of
      the EGF/PI3K/AKT pathway. 

PMID- 24748324
TI  - Purinergic signaling on leukocytes infiltrating the LPS-injured lung.
AB  - Extracellular nucleotides and nucleosides have been implicated as important
      signaling molecules in the pathogenesis of acute lung injury (ALI). While
      adenosine is known to inhibit T cell activation, little information is available
      as to ATP and NAD degrading enzymes, the expression of ATP and adenosine
      receptors/transporters in different T cell subsets. ALI was induced by
      challenging mice with intra-tracheal instillation of 60 ul (3 ug/g) LPS. After 3
      d and 7 d blood, lung tissue and bronchoalveolar lavage was collected and immune
      cells were analyzed using flow cytometry. The transcriptional phenotype of T
      helper cells, cytotoxic and regulatory T cells sorted by FACS was assessed by
      measuring the expression profile of 28 genes related to purinergic signaling
      using TaqMan Array Micro Fluidic Cards. Catabolism of ATP, NAD and cAMP by
      activated CD4+ T cells was evaluated by HPLC. CD73 was found to be highly
      abundant on lymphoid cells with little abundance on myeloid cells, while the
      opposite was true for CD39. After ALI, the abundance of CD39 and CD73
      significantly increased on all T cell subsets derived from lung tissue and
      bronchoalveolar space. Expression analysis in T cell subsets of the lung revealed
      ATP (Cd39, Cd73) and NAD (Cd38, Cd157, Cd296, Pc-1) degrading enzymes. However,
      only transcription of Cd38, Cd39, Cd73, Ent1 and A2a receptor was significantly
      upregulated after ALI in T helper cells. CD4+ T cells from injured lung rapidly
      metabolized extracellular ATP to AMP and adenosine but not NAD or cAMP. These
      findings show that lung T cells--the dominant cell fraction in the later phase of
      ALI--exhibit a unique expression pattern of purinergic signaling molecules.
      Adenosine is formed by T cells at an enhanced rate from ATP but not from NAD and
      together with upregulated A2a receptor is likely to modulate the healing process
      after acute lung injury.

PMID- 24748325
TI  - Viral CNS infections in children from a malaria-endemic area  of Malawi: a
      prospective cohort study.
AB  - BACKGROUND: Fever with reduced consciousness is an important cause of hospital
      admission of children in sub-Saharan Africa, with high mortality. Cerebral
      malaria, diagnosed when acute Plasmodium falciparum infection and coma are
      recorded with no other apparent reason, is one important cause. We investigated
      whether viruses could also be an important cause of CNS infection in such
      patients, and examined the relative contribution of viral pathogens and malaria
      parasitaemia. METHODS: We did a prospective cohort study in Blantyre, Malawi.
      From March 1, 2002, to Aug 31, 2004, we enrolled children aged between 2 months
      and 15 years who were admitted to hospital with suspected non-bacterial CNS
      infections. Children with a cerebrospinal fluid (CSF) white cell count of less
      than 1000 cells per MUL and negative bacterial microscopy and culture were deemed
      to have suspected viral CNS infection. Blood was examined for asexual forms of P
      falciparum. PCR was done on CSF or on post-mortem brain biopsy specimens to
      detect 15 viruses known to cause CNS infection. FINDINGS: Full outcome data were
      available for 513 children with suspected viral CNS infection, of whom 94 (18%)
      died. 163 children (32%) had P falciparum parasitaemia, of whom 34 (21%) died. At
      least one virus was detected in the CNS in 133 children (26%), of whom 43 (33%)
      died. 12 different viruses were detected; adenovirus was the most common,
      affecting 42 children; mumps, human herpes virus 6, rabies, cytomegalovirus,
      herpes simplex virus 1, and enterovirus were also important. 45 (9%) of the 513
      children had both parasitaemia and viral infection, including 27 (35%) of 78
      diagnosed clinically with cerebral malaria. Children with dual infection were
      more likely to have seizures than were those with parasitaemia alone, viral
      infection only, or neither (p<0.0001). 17 (38%) of the 45 children with dual
      infection died, compared with 26 (30%) of 88 with viral infection only, 17 (14%)
      of 118 with parasitaemia only, and 34 (13%) of 262 with neither (p<0.0001).
      Logistic regression showed children with a viral CNS infection had a
      significantly higher mortality than did those who did not have a viral CNS
      infection (p=0.001). INTERPRETATION: Viral CNS infections are an important cause
      of hospital admission and death in children in Malawi, including in children
      whose coma might be attributed solely to cerebral malaria. Interaction between
      viral infection and parasitaemia could increase disease severity. FUNDING:
      Wellcome Trust, US National Institutes of Health, and UK Medical Research
      Council.

PMID- 24748326
TI  - Investigation of antimicrobial resistance in Escherichia coli and enterococci
      isolated from Tibetan pigs.
AB  - OBJECTIVES: This study investigated the antimicrobial resistance of Escherichia
      coli and enterococci isolated from free-ranging Tibetan pigs in Tibet, China, and
      analyzed the influence of free-ranging husbandry on antimicrobial resistance.
      METHODS: A total of 232 fecal samples were collected from Tibetan pigs, and the
      disk diffusion method was used to examine their antimicrobial resistance. Broth
      microdilution and agar dilution methods were used to determine minimum inhibitory
      concentrations for antimicrobial agents for which disks were not commercially
      available. RESULTS: A total of 129 E. coli isolates and 84 Enterococcus isolates
      were recovered from the fecal samples. All E. coli isolates were susceptible to
      amoxicillin/clavulanic acid, and 40.4% were resistant to tetracycline. A small
      number of isolates were resistant to florfenicol (27.9%), ampicillin (27.9%),
      sulfamethoxazole/trimethoprim (19.4%), nalidixic acid (19.4%), streptomycin
      (16.2%) and ceftiofur (10.9%), and very low resistance rates to ciprofloxacin
      (7.8%), gentamicin (6.9%), and spectinomycin (2.3%) were observed in E. coli. All
      Enterococcus isolates, including E. faecium, E. faecalis, E. hirae, and E.
      mundtii, were susceptible to amoxicillin/clavulanic acid and vancomycin, but
      showed high frequencies of resistance to oxacillin (92.8%), clindamycin (82.1%),
      tetracycline (64.3%), and erythromycin (48.8%). Resistance rates to florfenicol
      (17.9%), penicillin (6.0%), ciprofloxacin (3.6%), levofloxacin (1.2%), and
      ampicillin (1.2%) were low. Only one high-level streptomycin resistant E. faecium
      isolate and one high-level gentamicin resistant E. faecium isolate were observed.
      Approximately 20% and 70% of E. coli and Enterococcus isolates, respectively,
      were defined as multidrug-resistant. CONCLUSIONS: In this study, E. coli and
      Enterococcus isolated from free-ranging Tibetan pigs showed relatively lower
      resistance rates than those in other areas of China, where more intensive farming
      practices are used. These results also revealed that free-range husbandry and
      absence of antibiotic use could decrease the occurrence of antimicrobial
      resistance to some extent.

PMID- 24748327
TI  - MicroRNAs: Novel Mechanism Involved in the Pathogenesis of Microwave Exposure on
      Rats' Hippocampus.
AB  - Microwave-induced adverse health outcomes have been gaining much attention in
      recent years. The hippocampus is sensitive and vulnerable to microwave exposure.
      Studies from our group and others showed that microwave-induced structural and
      functional injury of hippocampus, accompanied with alteration of gene and protein
      expression. It has been demonstrated that microRNAs (miRNAs) were involved in the
      physiological and pathological processes of brain. In this study, the miRNAs
      expression profiles of microwave-exposed hippocampus were detected by microarray
      analysis and verified by real-time polymerase chain reaction (PCR). At 7 days
      after 30 mW/cm(2) microwave exposure, the expression of 12 miRNAs increased,
      while other 70 miRNAs decreased in rats' hippocampus. However, most of miRNAs
      restored to normal levels at 14 days after exposure, only two upregulated miRNAs
      and 14 downregulated miRNAs were detected. Gene transcription, neuroprotection
      and receptors function related target genes were predicated by miRDB, miRbase and
      miRanda. Moreover, these differentially expressed miRNAs were involved in brain
      related signaling pathways, such as synaptic vesicle cycle, long-term depression,
      calcium signaling and neurotrophin signaling pathways. In conclusion, we
      successfully characterized the miRNA profiles in microwave-exposed hippocampus,
      and that will be helpful to clarify the molecular mechanism and provide potential
      therapeutic targets. 

PMID- 24748328
TI  - Spectrum of JAG1 gene mutations in Polish patients with Alagille syndrome.
AB  - Alagille syndrome (ALGS) is an autosomal dominant disorder characterized by
      developmental abnormalities in several organs including the liver, heart, eyes,
      vertebrae, kidneys, and face. The majority (90-94%) of ALGS cases are caused by
      mutations in the JAG1 (JAGGED1) gene, and in a small percent of patients (~1%)
      mutations in the NOTCH2 gene have been described. Both genes are involved in the
      Notch signaling pathway. To date, over 440 different JAG1 gene mutations and ten
      NOTCH2 mutations have been identified in ALGS patients. The present study was
      conducted on a group of 35 Polish ALGS patients and revealed JAG1 gene mutations
      in 26 of them. Twenty-three different mutations were detected including 13 novel
      point mutations and six large deletions affecting the JAG1 gene. Review of all
      mutations identified to date in individuals from Poland allowed us to propose an
      effective diagnostic strategy based on the mutations identified in the reported
      patients of Polish descent. However, the distribution of mutations seen in this
      cohort was not substantively different than the mutation distribution in other
      reported populations.

PMID- 24748329
TI  - Comparison of stem/progenitor cell number and transcriptomic profile in the
      mammary tissue of dairy and beef breed heifers.
AB  - Bovine mammary stem cells (MaSC) are a source of ductal and lobulo-alveolar
      tissue during the development of the mammary gland and its remodeling in
      repeating lactation cycles. We hypothesize that the number of MaSC, their
      molecular properties, and interactions with their niche may be essential in order
      to determine the mammogenic potential in heifers. To verify this hypothesis, we
      compared the number of MaSC and the transcriptomic profile in the mammary tissue
      of 20-month-old, non-pregnant dairy (Holstein-Friesian, HF) and beef (Limousin,
      LM) heifers. For the identification and quantification of putative
      stem/progenitor cells in mammary tissue sections, scanning cytometry was used
      with a combination of MaSC molecular markers: stem cell antigen-1 (Sca-1) and
      fibronectin type III domain containing 3B (FNDC3B) protein. Cytometric analysis
      revealed a significantly higher number of Sca-1(pos)FNDC3B(pos) cells in HF (2.94
      +/- 0.35%) than in LM (1.72 +/- 0.20%) heifers. In HF heifers, a higher
      expression of intramammary hormones, growth factors, cytokines, chemokines, and
      transcription regulators was observed. The model of mammary microenvironment
      favorable for MaSC was associated with the regulation of genes involved in MaSC
      maintenance, self-renewal, proliferation, migration, differentiation, mammary
      tissue remodeling, angiogenesis, regulation of adipocyte differentiation, lipid
      metabolism, and steroid and insulin signaling. In conclusion, the mammogenic
      potential in postpubertal dairy heifers is facilitated by a higher number of MaSC
      and up-regulation of mammary auto- and paracrine factors representing the MaSC
      niche.

PMID- 24748331
TI  - Sensitivity of global and regional terrestrial carbon storage to the direct CO2
      effect and climate change based on the CMIP5 model intercomparison.
AB  - Global and regional land carbon storage has been significantly affected by
      increasing atmospheric CO2 concentration and climate change. Based on fully
      coupled climate-carbon-cycle simulations from the Coupled Model Intercomparison
      Project Phase 5 (CMIP5), we investigate sensitivities of land carbon storage to
      rising atmospheric CO2 concentration and climate change over the world and 21
      regions during the 130 years. Overall, the simulations suggest that consistently
      spatial positive effects of the increasing CO2 concentrations on land carbon
      storage are expressed with a multi-model averaged value of 1.04 PgC per ppm. The
      stronger positive values are mainly located in the broad areas of temperate and
      tropical forest, especially in Amazon basin and western Africa. However, large
      heterogeneity distributed for sensitivities of land carbon storage to climate
      change. Climate change causes decrease in land carbon storage in most tropics and
      the Southern Hemisphere. In these regions, decrease in soil moisture (MRSO) and
      enhanced drought somewhat contribute to such a decrease accompanied with rising
      temperature. Conversely, an increase in land carbon storage has been observed in
      high latitude and altitude regions (e.g., northern Asia and Tibet). The model
      simulations also suggest that global negative impacts of climate change on land
      carbon storage are predominantly attributed to decrease in land carbon storage in
      tropics. Although current warming can lead to an increase in land storage of high
      latitudes of Northern Hemisphere due to elevated vegetation growth, a risk of
      exacerbated future climate change may be induced due to release of carbon from
      tropics.

PMID- 24748330
TI  - Increased response to glutamate in small diameter dorsal root ganglion neurons
      after sciatic nerve injury.
AB  - Glutamate in the peripheral nervous system is involved in neuropathic pain, yet
      we know little how nerve injury alters responses to this neurotransmitter in
      primary sensory neurons. We recorded neuronal responses from the ex-vivo
      preparations of the dorsal root ganglia (DRG) one week following a chronic
      constriction injury (CCI) of the sciatic nerve in adult rats. We found that small
      diameter DRG neurons (<30 um) exhibited increased excitability that was
      associated with decreased membrane threshold and rheobase, whereas responses in
      large diameter neurons (>30 um) were unaffected. Puff application of either
      glutamate, or the selective ionotropic glutamate receptor agonists alpha-amino-3
      hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and kainic acid (KA), or the
      group I metabotropic receptor (mGluR) agonist (S)-3,5-dihydroxyphenylglycine
      (DHPG), induced larger inward currents in CCI DRGs compared to those from
      uninjured rats. N-methyl-D-aspartate (NMDA)-induced currents were unchanged. In
      addition to larger inward currents following CCI, a greater number of neurons
      responded to glutamate, AMPA, NMDA, and DHPG, but not to KA. Western blot
      analysis of the DRGs revealed that CCI resulted in a 35% increase in GluA1 and a
      60% decrease in GluA2, the AMPA receptor subunits, compared to uninjured
      controls. mGluR1 receptor expression increased by 60% in the membrane fraction,
      whereas mGluR5 receptor subunit expression remained unchanged after CCI. These
      results show that following nerve injury, small diameter DRG neurons, many of
      which are nociceptive, have increased excitability and an increased response to
      glutamate that is associated with changes in receptor expression at the neuronal
      membrane. Our findings provide further evidence that glutamatergic transmission
      in the periphery plays a role in nociception. 

PMID- 24748333
TI  - On the reclassification of species assigned to Candida and other anamorphic
      ascomycetous yeast genera based on phylogenetic circumscription.
AB  - Multigene phylogenies have been instrumental in revising the classification of
      ascosporic (teleomorph) yeasts in a natural system based on lines of descent.
      Although many taxonomic changes have already been implemented for teleomorph
      taxa, this is not yet the case for the large genus Candida and smaller
      anascosporic (anamorph) genera. In view of the recently introduced requirement
      that a fungal species or higher taxon be assigned only a single valid name under
      the new International Code of Nomenclature for algae, fungi, and plants
      (Melbourne Code), the current species of Candida and other anamorph yeast genera
      must undergo revision to make genus membership consistent with phylogenetic
      affinities. A review of existing data and analyses shows that certain Candida
      species may be assigned to teleomorph genera with high confidence using multigene
      phylogenies. Candida species that form well-circumscribed phylogenetic clades
      without any teleomorph member justify the creation of new genera. However, a
      considerable number of Candida species sit at the end of isolated and often long
      branches, and hence cannot be assigned to larger species groups. They should be
      maintained in Candida sensu lato until studied by multigene analyses in datasets
      with comprehensive taxon sampling. The principle of name stability has to be
      honoured to the largest extent compatible with a natural classification of
      Candida species. 

PMID- 24748332
TI  - Significance of exercise in nonalcoholic fatty liver disease in men: a community
      based large cross-sectional study.
AB  - BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is a risk factor for
      diabetes and cardiovascular disease that could progress to nonalcoholic
      steatohepatitis, cirrhosis, and liver failure. We aimed to assess the
      relationship between NAFLD and lifestyle habits. METHODS: Using a community
      based, cross-sectional design, the records of 11,094 Japanese subjects who had
      undergone at least 1 annual health checkup were reviewed. RESULTS: Of the 6,370
      subjects who qualified for enrolment, 1,346 met the diagnostic criteria for
      NAFLD. The prevalence rate (PR) of NAFLD increased significantly to 36.6, 41.5,
      and 41.1 % with no snacking, snacking less than once/day, and snacking >=2
      times/day, respectively, in men (P = 0.0495) and to 10.8, 11.7, and 15.3 %,
      respectively, in women (P = 0.002). In men, the NAFLD PR decreased significantly
      to 48.8, 36.9, and 29.9 % with no exercise, exercise consciousness, and
      periodical exercise, respectively (P < 0.001). In women, the NAFLD PR decreased
      significantly to 19.3, 13.5, 11, and 8 % with sleep durations of <=4, 5-6, 7-8,
      and >=9 h, respectively (P = 0.003). Periodical exercise was identified as an
      independent factor associated with NAFLD in men (odds ratio 0.707, 95 %
      confidence interval 0.546-0.914; P = 0.008). CONCLUSIONS: Performing regular
      exercise was associated with a reduced risk for NAFLD in men. Men with a high
      risk for NAFLD can be identified using questionnaires on exercise in an
      outpatient setting. Disease progression and further complications may be
      prevented by educating high-risk NAFLD patients about the importance of exercise.

PMID- 24748334
TI  - Identification and characterisation of xylanolytic yeasts isolated from decaying
      wood and sugarcane bagasse in Brazil.
AB  - In this study, yeasts associated with lignocellulosic materials in Brazil,
      including decaying wood and sugarcane bagasse, were isolated, and their ability
      to produce xylanolytic enzymes was investigated. A total of 358 yeast isolates
      were obtained, with 198 strains isolated from decaying wood and 160 strains
      isolated from decaying sugarcane bagasse samples. Seventy-five isolates possessed
      xylanase activity in solid medium and were identified as belonging to nine
      species: Candida intermedia, C. tropicalis, Meyerozyma guilliermondii,
      Scheffersomyces shehatae, Sugiyamaella smithiae, Cryptococcus diffluens, Cr.
      heveanensis, Cr. laurentii and Trichosporon mycotoxinivorans. Twenty-one isolates
      were further screened for total xylanase activity in liquid medium with xylan,
      and five xylanolytic yeasts were selected for further characterization, which
      included quantitative analysis of growth in xylan and xylose and xylanase and
      beta-D-xylosidase activities. The yeasts showing the highest growth rate and cell
      density in xylan, Cr. laurentii UFMG-HB-48, Su. smithiae UFMG-HM-80.1 and Sc.
      shehatae UFMG-HM-9.1a, were, simultaneously, those exhibiting higher xylanase
      activity. Xylan induced the highest level of (extracellular) xylanase activity in
      Cr. laurentii UFMG-HB-48 and the highest level of (intracellular, extracellular
      and membrane-associated) beta-D-xylosidase activity in Su. smithiae UFMG-HM-80.1.
      Also, significant beta-D-xylosidase levels were detected in xylan-induced
      cultures of Cr. laurentii UFMG-HB-48 and Sc. shehatae UFMG-HM-9.1a, mainly in
      extracellular and intracellular spaces, respectively. Under xylose induction, Cr.
      laurentii UFMG-HB-48 showed the highest intracellular beta-D-xylosidase activity
      among all the yeast tested. C. tropicalis UFMG-HB 93a showed its higher
      (intracellular) beta-D-xylosidase activity under xylose induction and higher at
      30  degrees C than at 50  degrees C. This study revealed different xylanolytic
      abilities and strategies in yeasts to metabolise xylan and/or its hydrolysis
      products (xylo-oligosaccharides and xylose). Xylanolytic yeasts are able to
      secrete xylanolytic enzymes mainly when induced by xylan and present different
      strategies (intra- and/or extracellular hydrolysis) for the metabolism of xylo
      oligosaccharides. Some of the unique xylanolytic traits identified here should be
      further explored for their applicability in specific biotechnological processes. 

PMID- 24748335
TI  - Gemcitabine and oxaliplatin chemotherapy for advanced hepatocellular carcinoma
      after failure of anti-angiogenic therapies.
AB  - BACKGROUND: Sorafenib is the only systemic treatment that has shown a significant
      benefit in overall survival (OS) and in progression-free survival (PFS) in
      advanced hepatocellular carcinoma (HCC) patients. No standard of care currently
      exists for second-line treatment. The association of Gemcitabine-Oxaliplatine
      (GEMOX) has shown efficacy in the first-line setting. The aim of this study was
      to evaluate the efficacy of GEMOX after failure of at least one line of anti
      angiogenic (AA) therapy. PATIENT AND METHODS: We performed a multicenter
      retrospective analysis of advanced HCC patients that received GEMOX chemotherapy
      after progression on at least one line of AA therapy. RESULTS: We analyzed a
      total of 40 patients that received a median of 7 cycles of GEMOX over a 6-year
      period. Grade 3/4 toxicity was observed in 25 % of patients, mainly
      neurotoxicity, thrombocytopenia and neutropenia in 12.5 %, 5 % and 5 % of
      patients respectively. Grade <3 toxicity was mainly hematological and
      neurotoxicity. In the sub-cohort of 35 patients evaluable for response, partial
      response was observed in 20 % of patients, while 46 % had stable disease. Median
      OS was 8.3 months, with a 6-month OS rate of 59 %. Median PFS was 3.1 months.
      Prognostic factors for OS in univariable analysis were the performance status and
      AFP levels at GEMOX start, and the BCLC score at diagnosis. None of these factors
      were prognostic for PFS or tumor response. CONCLUSION: The GEMOX schedule seems
      to show clinical activity and an acceptable toxicity profile in advanced HCC
      patients who progressed after anti-angiogenic treatment. The observed median OS
      of over 8 months is encouraging in this population of heavily pretreated
      patients. These results would merit confirmation in a prospective randomized
      study.

PMID- 24748336
TI  - The ability of molecular docking to unravel the controversy and challenges
      related to P-glycoprotein--a well-known, yet poorly understood drug transporter.
AB  - P-glycoprotein is the most crucial membrane transporter implicated in tumor
      resistance. Intensive efforts were paid to elucidate the complex mechanism of
      transport and to identify modulators of this transporter. However, the borderline
      between substrates and modulators is very thin and identification of the binding
      sites within P-glycoprotein is complex. Herein, we provide an intensive review of
      those issues and use molecular docking to assess its ability: first, to
      differentiate between three groups (substrates, modulators and non-substrates)
      and second to identify the binding sites. After thorough statistical analysis, we
      conclude despite the various challenges that molecular docking should not be
      underestimated as differences between the distinct groups were significant.
      However, when it comes to defining the binding site, care must be taken, since
      consensus throughout literature could not be reached. 

PMID- 24748337
TI  - Overexpression of long noncoding RNA HOTAIR predicts a poor prognosis in patients
      with cervical cancer.
AB  - PURPOSE: The long noncoding RNA HOTAIR has been reported to be a good biomarker
      for poor prognosis in a variety of human cancers. However, whether HOTAIR could
      serve as novel biomarker to predict prognosis in cervical cancer or not is
      unknown. The aim of the present study was to examine the expression of HOTAIR in
      cervical cancers and to investigate the relationship between this lncRNA
      expression levels and existing clinicopathological factors and patient survival.
      METHODS: We examined the expression of HOTAIR in 218 cervical cancer tissues and
      matched 218 adjacent normal tissues using quantitative real-time RT-PCR and
      analyzed its correlation with the clinical parameters. RESULTS: The results
      showed that HOTAIR expression in cervical cancer tissues was significantly
      upregulated compared with the matched nontumorous tissues (P < 0.0001). Increased
      HOTAIR expression was significantly correlated with FIGO stage (P < 0.0001),
      lymph node metastasis (P < 0.0001), depth of cervical invasion (P < 0.0001),
      tumor size (P = 0.006) and age (P = 0.020), but not other clinical
      characteristics. Moreover, cervical cancer patients with HOTAIR higher expression
      have shown significantly poorer overall survival (P < 0.0001) and disease-free
      survival (P < 0.0001) than those with lower HOTAIR expression. Univariate (P <
      0.0001, HR = 4.566, 95 % CI 2.122-9.825) and multivariate (P = 0.012, HR = 2.863,
      95 % CI 1.263-76.490). Cox regression analyses showed that HOTAIR expression
      served as an independent predictor for overall survival. CONCLUSIONS: our data
      indicate that high expression of HOTAIR is involved in cervical cancer
      progression and could be a potential target for diagnosis and gene therapy.

PMID- 24748339
TI  - Difference of endothelial function during pregnancies as a method to predict
      preeclampsia.
AB  - BACKGROUND: Systemic endothelial dysfunction has been identified as one of the
      main events in preeclampsia (PE). A nonhealthy vascular endothelium can be
      pointed out as the pathophysiological explanation of the clinical manifestations
      and complications of PE. Once normal pregnancy is characterized by a constant
      increase in endothelial function, a follow-up of this physiological event could
      be used as an early marker or a prediction tool to predict PE. OBJECTIVES: To
      perform a longitudinal assessment of endothelial function, using an ultrasound
      study of brachial artery flow Flow-mediated dilation (FMD), in normotensive and
      preeclamptic pregnancies, to evaluate the difference of FMD values along the
      second trimester of pregnancy to predict PE. PATIENTS AND METHODS: In a
      prospective cohort study, 91 pregnant women with a high risk of developing PE
      were subjected to FMD of the brachial artery. The difference in the FMD values,
      between 16(+0) and 19(+6) and 24(+0) and 27(+6) weeks of gestation were compared,
      taking PE development into consideration. Receiver operator characteristics (ROC)
      curves were created to determine the sensibility and specificity of FMD
      difference to predict PE. RESULTS: A total of 19 patients developed PE and the
      other 72 women remained normotensive until 1 week after delivery. When
      considering a cut off of +2.50 %, FMD difference, between the two evaluations,
      sensitivity for PE prediction was 87.5 % for early onset PE and 95.5 % for late
      PE. CONCLUSION: The difference of FMD values between the second trimester of
      pregnancy can be used for PE prediction for both, early and late forms of PE.

PMID- 24748338
TI  - Does cabergoline help in decreasing endometrioma size compared to LHRH agonist? A
      prospective randomized study.
AB  - AIM: The aim of this study was to compare the efficiency of dopamine agonist,
      Cabergoline, in decreasing the size of endometrioma, with that of luteinizing
      hormone releasing hormone (LHRH) agonist, triptorelin acetate. STUDY: This was a
      prospective, randomized study. SETTING: The setting was in two private medical
      centers in the UAE, from January 2011 to February 2012. PATIENTS AND METHODS: One
      hundred and forty patients complaining of endometrioma, and fulfilling the
      eligibility criteria, were chosen and divided into two groups as follows: Group I
      comprised 71 patients; all of them received Cabergoline tablets, 0.5 mg tablets,
      twice per week for 12 weeks. Group II comprised 69 patients; all of them received
      LHRH agonist, decapeptyl, 3.75 mg subcutaneous, single injection, once a month
      for 3 months. All patients underwent vaginal ultrasound before and after the
      treatment period to compare the change in the size of endometrioma by the same
      sonography team in each hospital that was blind to the treatment groups. OUTCOME:
      The outcome was measured by the changes in the endometrioma size by vaginal
      ultrasound after completion of the 3 months' treatment period. The management
      line was considered to be significantly effective if the endometrioma size was
      reduced by more than 25 % of its original pretreatment size. RESULTS: Group I: 46
      out of the 71 patients (64.7 %) had significant decrease in endometrioma size.
      Group II: 15 out of 69 patients (21.7 %) had significant decrease in endometrioma
      size. Paired t test to compare the means of the two groups was highly significant
      (p < 0.05) CONCLUSION: Cabergoline (dostinex) yields better results in decreasing
      the size of endometrioma, compared to LHRH-agonist by exerting antiangiogenic
      effects through vascular endothelial growth factor receptor-2 (VEGFR-2)
      inactivation. It has no major side effects, easier to administer, and cheaper
      than LHRH agonists.

PMID- 24748340
TI  - Hand and wrist complaints in pregnancy.
AB  - PURPOSE: Hand and wrist complaints can decrease the quality of life of pregnant
      women, which can occur or aggravate during pregnancy and advance to chronic state
      if left untreated. The purpose of this study was to describe hand and wrist
      complaints in relation to pregnancy and assess their significance in pregnancy.
      METHODS: In a prospective cross-sectional study, 383 participants were randomly
      selected from among pregnant women on or over 28 weeks of gestation, attending
      the primary care maternal health clinic in a university hospital. The prevalence
      and severity of hand and wrist complaints were assessed using the Boston Carpal
      Tunnel Questionnaire (BCTQ). The symptomatic pregnant women were consulted by an
      orthopedist. The specific diagnoses of the patients were made based on patient
      history and physical examination. RESULTS: According to BCTQ scoring 258 (67.4 %)
      pregnant women were symptomatic. The diagnoses were as follows: asymptomatic 125
      (32.6 %), nonspecific symptoms 138 (36 %), tendinitis 80 (20.9 %), carpal tunnel
      syndrome (CTS) 39 (10.2 %) and cubital syndrome 1 (0.3 %). There was no
      association noted between the diagnoses and numbers of pregnancies, occupational
      status, age, gestational weeks, weight gain or body mass index (BMI) (p > 0.05).
      CONCLUSION: The prevalence of hand and wrist complaints is high in pregnant
      women. All pregnant women should be investigated for hand and wrist complaints in
      routine antenatal checks to ensure good life quality during pregnancy and for
      avoiding these complaints advancing to chronic state. Further studies are needed
      to evaluate the effect of musculoskeletal systems disorders in pregnancy.

PMID- 24748341
TI  - Analysis of microscopic tumor spread patterns according to gross morphologies and
      suggestions for optimal resection margins in bile duct cancer.
AB  - BACKGROUND/PURPOSE: Surgical resection is the only curative treatment for
      extrahepatic bile duct (EHBD) cancer, but guidelines for optimal resection
      margins have not yet been established. Therefore, the purpose of this study is to
      analyze the patterns of microscopic tumor spreads and their lengths according to
      gross morphology and to suggest optimal resection margins for EHBD cancer.
      METHODS: A total of 79 patients with EHBD cancers who underwent curative
      resection at Seoul National University Hospital between 2007 and 2010 were
      reviewed. Pathologic findings were reviewed by a single specialized pathologist.
      RESULTS: Mucosal and mural/perimural spreads were seen in 37.3 and 62.3 %,
      respectively. The mean length of tumor spreads in the papillary (n = 13),
      nodular/nodular infiltrative (n = 43), and sclerosing types (n = 23) were 4.5 +/-
      6.3, 1.8 +/- 6.4, and 6.4 +/- 6.7 mm, respectively. Spread patterns correlated
      with gross morphologies (P < 0.001). The lengths of tumor spreads at the 90th
      percentile were 15.6, 10.0, and 15.6 mm, respectively. CONCLUSIONS: The patterns
      of tumor spreads correlated with gross morphologies. Optimal resection margins in
      EHBD cancers should be 16 mm in the papillary and sclerosing types and 10 mm in
      the nodular/nodular infiltrative type.

PMID- 24748342
TI  - Will there be a good general surgeon when you need one? (Part II) Solutions and
      taking back general surgery.
AB  - INTRODUCTION: Multiple reports have cited the looming shortage of physicians over
      the next decades related to increasing demand, an aging of the population, and a
      stagnant level in the production of new physicians. General surgery shares in
      this problem, and the specialty is "stressed" by a declining workforce related to
      increasing specialization that leaves gaps in emergency, trauma, and rural
      surgical care. SUMMARY: The Society of Surgery of the Alimentary Tract (SSAT)
      Public Policy and Advocacy Committee sponsored panel discussions regarding the
      general surgery workforce shortage at the Digestive Disease Week 2012 and 2013
      meetings. The 2012 panel focused on defining the problem. This is the summation
      of the series with the solutions to the general surgery workforce shortage as
      offered by the 2013 panel.

PMID- 24748343
TI  - Modified nucleobases.
AB  - Various molecules which are similar to the natural nucleobases exist in nature or
      have been synthetically developed. In this chapter we review work on the
      photophysical properties of several modified nucleobases, focusing particularly
      on how these properties differ from those of the natural nucleobases. We discuss
      studies that give physical insight into how the molecular structure can be
      related to photophysical properties with many of these studies being theoretical.
      One useful photophysical property is the ability to fluoresce with high quantum
      yields. Natural bases practically do not fluoresce, so being able to design
      molecules that fluoresce is a goal of practical importance. Many of the modified
      nucleobases discussed in this review are fluorescent analogues, analogues that
      have very different fluorescent properties from the natural bases. The studies
      reviewed here may provide ways to design other analogues with a set of desired
      properties. 

PMID- 24748345
TI  - Surgical Ethics Symposium "Ethical dilemmas in surgical practice".

PMID- 24748344
TI  - The microbial diversity of traditional spontaneously fermented lambic beer.
AB  - Lambic sour beers are the products of a spontaneous fermentation that lasts for
      one to three years before bottling. The present study determined the microbiota
      involved in the fermentation of lambic beers by sampling two fermentation batches
      during two years in the most traditional lambic brewery of Belgium, using culture
      dependent and culture-independent methods. From 14 samples per fermentation, over
      2000 bacterial and yeast isolates were obtained and identified. Although minor
      variations in the microbiota between casks and batches and a considerable species
      diversity were found, a characteristic microbial succession was identified. This
      succession started with a dominance of Enterobacteriaceae in the first month,
      which were replaced at 2 months by Pediococcus damnosus and Saccharomyces spp.,
      the latter being replaced by Dekkera bruxellensis at 6 months fermentation
      duration. 

PMID- 24748346
TI  - Colon interposition graft for corrosive esophageal stricture: midterm functional
      outcome.
AB  - BACKGROUND: Corrosive esophageal stricture is a major cause of morbidity among
      Nigerians. In most cases, this follows accidental or parasuicidal ingestion of
      caustic sodium hydroxide solution (NaOH) often used in the local production of
      soaps. Various treatment modalities have been advocated for the treatment of
      esophageal stricture. In this study, we review the results of our adopted
      technique in the past 10 years for pedicled colonic interposition. METHODS: This
      is a retrospective study of 21 patients who underwent substernal isoperistaltic
      pedicled colonic interposition graft for management of corrosive esophageal
      stricture. The right colon was pulled up into the neck in all the patients
      without resecting the strictured esophagus. RESULTS: Long segment strictures and
      multiple strictures were the main indications for the procedure. The mean
      duration of the procedure was 339.6 +/- 71.1 min. The average intraoperative
      blood loss was 673.1 +/- 398.1 mL. There were two (9.5 %) hospital mortalities.
      Graft infarction (9.5 %), cervical fistulae (19.0 %), and reflux neo-esophagitis
      (14.3 %) were the main non-fatal complications. In the mid-term, dysphagia was
      completely relieved in a little over 84 % (16/19) of patients, while one patient
      (4.8 %) still experienced reflux neo-esophagitis requiring treatment. There was
      no case of gross regurgitation or nocturnal aspiration in the mid-term.
      CONCLUSIONS: Although the use of pedicled colonic interposition graft offers a
      good mid-term functional outcome with relief of dysphagia, early postoperative
      morbidity is high. Graft infarction is the single most important factor for poor
      functional outcome and every effort must be made to prevent its occurrence.

PMID- 24748347
TI  - Audit on preoperative fasting of elective surgical patients in an African
      academic medical center.
AB  - BACKGROUND: Preoperative fasting is a requisite before anesthesia. The main
      reason for preoperative fasting is to reduce gastric volume and acidity and thus
      decrease the risk of pulmonary aspiration. However, preoperative fasting is
      usually prolonged beyond the recommended time for various reasons. Despite the
      many adverse effects of prolonged fasting, patients sometimes fasted for a
      prolonged time when surgery was delayed for different reasons at the University
      of Gondar Hospital. The aim of this study was to assess the duration of
      preoperative fasting for elective surgery. METHODS: A cross-sectional study was
      conducted from March 10 to April 10, 2013. Patients were interviewed 24 h after
      surgery. All 43 patients who were under anesthesia while operated on during the
      study period were included. RESULT: Of the 43 patients included in the study, 35
      were adults and 8 were children. The minimum, maximum, and mean fasting hours for
      food were 5, 96, and 19.60, respectively, and more than 50 % of the patients
      fasted from food twice as long as recommended. The minimum, maximum, and mean
      fasting hours for fluid were 5, 19, and 12.72, respectively. More than 95 % of
      the patients fasted from fluid longer than recommended. CONCLUSION: Most patients
      fasted from both food (92 %) and fluid (95 %) longer than the fasting time
      recommended by the AAGBI, ASA, RCOA, and RCN fasting guidelines. Anesthetists,
      surgeons, and nurses need to revise operation lists every day in the operating
      theatres and resuscitate the patients when surgery is delayed for various
      reasons. A preoperative fasting guideline should be developed and implemented in
      the University of Gondar Hospital.

PMID- 24748348
TI  - Does working memory training promote the use of strategies on untrained working
      memory tasks?
AB  - Adaptive computerized training has been associated with significant enhancements
      in untrained working memory tasks, but the nature of the cognitive changes that
      underpin these improvements are not yet fully understood. Here, we investigate
      the possibility that training stimulates the use of memory-related strategies. In
      a randomized controlled trial, participants completed four tests of working
      memory before receiving adaptive working memory training, nonadaptive working
      memory training with low memory loads, or no training. Open-ended interviews
      about strategy use were conducted after the administration of untrained working
      memory tasks at two time points. Those in the adaptive and nonadaptive groups
      completed the assessments before (T1) and after (T2) 10 training sessions. The no
      training group completed the same set of tasks at T1 and T2, without any training
      between assessment points. Adaptive training was associated with selective
      improvements in untrained tests of working memory, accompanied by a significant
      increase in the use of a grouping strategy for visuospatial short-term memory and
      verbal working memory tasks. These results indicate that training-related
      improvements in working memory may be mediated by implicit and spontaneous
      changes in the use of strategies to subsegment sequences of information into
      groups for recall when the tasks used at test overlap with those used during
      training.

PMID- 24748349
TI  - Reforms in medical education: optimizing quantity and quality.

PMID- 24748350
TI  - Breast and cervical cancer risk in India: an update.
AB  - BACKGROUND: Breast and cervical cancers are two major cancers among Indian women.
      Analysis of trends would help in planning and organization of programs for
      control of these cancers. OBJECTIVE: The objective of the following study is to
      compute risk of breast and cervical cancers using updated data from different
      cancer registries of India and study of its trends. MATERIALS AND METHODS: Data
      on incidence rates of breast and cervical cancers were obtained from six major
      cancer registries of India for the years 1982-2008 and from the recently
      initiated cancer registries, North Eastern Registries of India with a total of 21
      registries. Annual percent change in incidence and risk in terms of one in number
      of women likely to develop cancer was estimated for both the cancers in various
      registries. RESULTS: The annual percentage change in incidence ranged from 0.46
      to 2.56 and -1.14 to -3.4 for breast and cervical cancers respectively. Trends
      were significant for both cancers in the registries of Chennai, Bangalore, Mumbai
      and Delhi except Barshi and Bhopal. North East region showed decrease in risk for
      breast and cervical cancers whereas increasing trend was observed in Imphal
      (West) and for cervical cancer in Silchar. CONCLUSION: North Eastern region
      recorded decline in the incidence of breast cancer which is contrary to the
      observation in other registries, which showed increase in breast cancer and
      decline in cervical cancer incidences.

PMID- 24748351
TI  - Functional disability among elderly persons in a rural area of Haryana.
AB  - BACKGROUND: The number and proportion of elderly persons is increasing, in India,
      as well as the world. Disability is an important indicator to measure disease
      burden in this group. While some chronic conditions may not be amenable to
      complete cure, their functional disabilities can be improved with timely and
      appropriate management. OBJECTIVES: The objective of the following study is to
      estimate the prevalence of functional disability and study its association with
      socio-demographic variables and self-reported chronic conditions among elderly
      persons in a rural area of Haryana. MATERIALS AND METHODS: All persons aged 60
      years and above in the randomly selected six clusters were included in this
      community-based cross-sectional study. Information was collected on socio
      demographic variables and self-reported chronic conditions. Functional disability
      was defined as having disability in activities of daily living, or blindness or
      hearing impairment, or a combination of these. In multivariate analysis, backward
      stepwise logistic regression was carried out to study the association between the
      independent and dependent variables, after adjusting for confounding variables.
      RESULTS: Among the 836 participants studied, the prevalence of functional
      disability was estimated to be 37.4% (95% confidence interval: 34.2, 40.7). The
      prevalence was less among men (35.9%) than women (38.8%). The prevalence
      increased with age, was more common among persons who were not currently married,
      had diabetes and chronic obstructive pulmonary disease. CONCLUSION: Functional
      disability is common among elderly persons in the rural area. Community-based
      interventions are needed to address them. Management of chronic conditions should
      include prevention and control of associated disability.

PMID- 24748352
TI  - Epidemiological profile of snake bite in south 24 Parganas district of West
      Bengal with focus on underreporting of snake bite deaths.
AB  - BACKGROUND: Snake bite is a neglected public health problem in India. Very few
      community based epidemiological studies in India have been published so far on
      this issue. Most of the studies were carried out on hospital data. Previous
      community-based survey in the state revealed that only 22% snake bite victims
      attended hospitals. OBJECTIVES: The objective of the present study is to find out
      the epidemiological profile of snake bite in eight blocks of the South 24
      Paraganas district of West Bengal and to explore the under reporting of snake
      bite deaths in health facilities in that area during the study period. MATERIALS
      AND METHODS: A retrospective analysis of snake bite data was carried out from a
      community-based epidemiological survey on 1.9 million populations. This survey
      was done door-to-door from January 2009 to October 2010 to get epidemiological
      profile of snake bite of the previous 2 years. The data of direct survey was
      compared with the official report of the same area to evaluate the hospital-based
      data with focus on underreporting of snakebite deaths. RESULTS: A total number of
      snake bite cases as found in the survey in the study area was 4871. There was a
      huge gap between the two data (direct survey and official data). Only 7.23% snake
      bite deaths were officially reported. Only 22.19% of the snake bite victims
      attended the hospitals. Nearly 65.7% of the snake bite deaths were due to common
      krait bite, most of them occurring in the months of June to September.
      CONCLUSIONS: Official reporting system is still having a huge deficiency in
      India. Snake bite needs to get more attention from the health authority.

PMID- 24748353
TI  - Effect of very early skin to skin contact on success at breastfeeding and
      preventing early hypothermia in neonates.
AB  - CONTEXT: Birth and immediate postpartum period pose many challenges for the
      newborn. The neonatal mortality rates are high in India, whereas the
      breastfeeding rates are still low. Hence, need exists for a simple and easily
      applicable intervention, which may counter these challenges. AIMS: The present
      study was undertaken to evaluate the effects of very early skin-to-skin contact
      (SSC), in term babies with their mothers, on success of breastfeeding and
      neonatal well-being. SETTINGS AND DESIGN: Randomized control trial conducted over
      2 years' period in a tertiary care hospital. MATERIALS AND METHODS: Healthy
      babies delivered normally were included. Very early SSC between mothers and their
      newborns was initiated in the study group. We studied effective suckling (using
      modified infant breastfeeding assessment tool [IBFAT]), breastfeeding status at 6
      weeks, maternal satisfaction, thermal regulation, baby's weight and morbidity.
      STATISTICAL ANALYSIS: T-test, Pearson Chi-square test and non-parametric Mann
      Whitney test were used through relevant Windows SPSS software version 16.0.
      RESULTS: We observed that SSC contributed to better suckling competence as
      measured by IBFAT score (P < 0.0001). More babies in the SSC group were
      exclusively breastfed at first follow-up visit (P = 0.002) and at 6 weeks (P <
      0.0001). SSC led to higher maternal satisfaction rates, better temperature gain
      in immediate post-partum period, lesser weight loss was at discharge and at first
      follow-up (all P < 0.0001) and lesser morbidity than the study group (P = 0.006).
      CONCLUSION: Very early SSC is an effective intervention that improves baby's
      suckling competence, maternal satisfaction, breastfeeding rates and temperature
      control and weight patterns.

PMID- 24748354
TI  - Utilization of maternal and child health services in western rural Nepal: a cross
      sectional community-based study.
AB  - BACKGROUND: Considering the commitment and investment of Nepal to reduce maternal
      and child mortality, understanding service utilization and factors associated
      with a child and maternal health services is important. OBJECTIVES: This study
      was examined the factors associated with utilization of maternal and child health
      services in Kapilvastu District of Nepal. MATERIALS AND METHODS: A cross
      sectional study was conducted in 2010 by interviewing 190 mothers having children
      of aged 12-23 months using the standardized questionnaire. RESULTS: Immunization
      status (97.4%) and vitamin A supplementation (98.4%) was high. However,
      initiation of breastfeeding within an hour of birth was low (45.3%) and 63.2% had
      practiced exclusive breastfeeding. Majority (69.5%) of respondents delivered
      their child at home and 39.5% sought assistance from health workers. The mothers
      who did not have any education, mothers from Dalit/Janjati and the Terai origin
      were less likely to deliver at the health facility and to seek the assistance of
      health workers during childbirth. CONCLUSION: The immunization program coverage
      was high, whereas maternal health service utilization remained poor.
      Interventions that focus on mothers from Dalit/Janjati group and with lower
      education are likely to increase utilization of maternal health services.

PMID- 24748355
TI  - Engagement of National Board of Examinations in strengthening public health
      education in India: present landscape, opportunities and future directions.
AB  - A trained and adequate heath workforce forms the crux in designing, implementing
      and monitoring health programs and delivering quality health services. Education
      is recognized as a critical instrument for creating such trained health
      professionals who can effectively address the 21 st century health challenges. At
      present, the Public Health Education in India is offered through medical colleges
      and also outside the corridors of medical colleges which was not the scenario
      earlier. Traditionally, Public Health Education has been a domain of medical
      colleges and was open for medical graduates only. In order to standardize the
      Postgraduate Medical Education in India, the National Board of Examinations (NBE)
      was set up as an independent autonomous body of its kind in the country in the
      field of medical sciences with the prime objective of improving the quality of
      the medical education. NBE has also played a significant role in enhancing Public
      Health Education in India through its Diplomat of National Board (DNB) Programs
      in Social and Preventive Medicine, Health and Hospital Administration, Maternal
      and Child Health, Family Medicine and Field Epidemiology. It envisions creating a
      cadre of skilled and motivated public health professionals and also developing a
      roadmap for postgraduate career pathways. However, there still exists gamut of
      opportunities for it to engage in expanding the scope of Public Health Education.
      It can play a key role in accreditation of public health programs and
      institutions which can transform the present landscape of education of health
      professionals. It also needs to revisit and re-initiate programs like DNB in
      Tropical Medicine and Occupational Health which were discontinued. The time is
      imperative for NBE to seize these opportunities and take necessary actions in
      strengthening and expanding the scope of Public Health Education in India. 

PMID- 24748356
TI  - Non-adherence to life-style modification and its factors among type 2 diabetic
      patients.
AB  - Non-adherence to preventive and therapeutic life-style recommendations among
      patients with diabetes is special challenge in the management of these patients.
      This study aimed to measure the proportion of non-adherence to life-style
      modification and factors associated with these among a group of Bangladeshi type
      2 diabetic patients. Under an analytical cross-sectional design 374 type 2
      diabetic patients (age >20 years), diagnosed for at least 1 year, were selected
      from different health care centers operated by the Diabetic Association of
      Bangladesh. Non-adherence rate were assessed for: Diet (88%), exercise (25%),
      routine blood glucose testing (32%), foot care (70%), smoking (6%) and betel quid
      chewing habit (25%). Binary logistic regression suggests that higher education
      group (P = 0.013), rural area (P = 0.013) and attendance to diabetes education
      classes (P = 0.043) showed good adherence to diet and non-attendance to diabetes
      education class (P = 0.014), older age (P = 0.037) are associated to non
      adherence to exercise. Unemployed patients showed more non-adherence to blood
      glucose testing (P = 0.045) than others. Non-attendance to diabetes education
      class (P = 0.037) and business occupation group (P = 0.039) showed significant
      association to smoking and betel quid intake habit respectively. 

PMID- 24748357
TI  - Prevalence of chronic obstructive pulmonary disease and its association with
      tobacco smoking and environmental tobacco smoke exposure among rural population.
AB  - A field survey was conducted for chronic obstructive pulmonary disease (COPD)
      epidemiology in the rural field practice area of Kempegowda Institute of Medical
      Sciences, Bangalore, India, which covers a population of 44,387 to find out the
      prevalence of COPD in adult subjects of 35 years and above using cluster sampling
      technique and to determine the association of tobacco smoking, environmental
      tobacco smoking (ETS) exposure and type of cooking fuel used with COPD. The
      overall prevalence of COPD was 4.36%. The prevalence among males and females were
      5.32% and 3.41% respectively. The prevalence was found to be increasing with an
      increase in age. The tobacco smoke and exposure to ETS was significantly
      associated with higher odds of COPD with adjusted odds ratio 2.97 and 2.67
      respectively. Thus, there was a significant association between tobacco smoking
      and ETS exposure with COPD. 

PMID- 24748358
TI  - A study on smoking and associated psychosocial factors among adolescent students
      in Kolkata, India.
AB  - Tobacco use among school children and adolescents is an increasing problem world
      wide, particularly in the developing countries. A cross-sectional observational
      study was carried out in six co-educational high schools in Kolkata, West Bengal
      among 526 students of 15-19 years to determine the prevalence of smoking and to
      find out any difference among the smokers and non-smokers regarding factors
      related to family relations, peer group and personal characteristics. The overall
      rate of smoking was found to be 29.6%, mean age of initiation of smoking was
      earlier in males. Among smokers 75% students started smoking by 15 years. Smoking
      of father and peer group, family conflict and pornography addiction were found to
      have significant association with smoking of students. Early school health based
      interventions addressing these factors might help in effectively tackling this
      problem. 

PMID- 24748359
TI  - Gross congenital malformation at birth in a government hospital.
AB  - A hospital-based cross-sectional study was undertaken to determine proportion of
      gross congenital malformation (GCMF) occurring at intramural births. Rate of GCMF
      was found to be 16.4/1000 consecutive singleton births (>28 weeks) with three
      leading malformation as anencephaly (44.68%), talipes equinovarus (17.02%) and
      meningomyelocele (10.63%). Higher risk of malformed births were noticed amongst
      un-booked (2.07%) in-comparison to booked (1.01%) mothers; women with low level
      of education (up to 8 years [2.14%] vs. at least 9 years of schooling [0.82%]);
      gravida status of at least 3 (2.69%) followed by 1 (1.43%) and 2 (1.0%)
      respectively; pre-term (5.13%) vs. term (0.66%); cesarean section (4.36%) versus
      vaginal delivery (0.62%). Mortality was significantly higher among congenitally
      malformed (17.35%) than normal (0.34%) newborns. With-in study limitation,
      emergence of neural tube defect as the single largest category of congenital
      malformation indicates maternal malnutrition (especially folic acid) that needs
      appropriate attention and management. 

PMID- 24748360
TI  - Morbidity among iron ore mine workers in Goa.
AB  - This study was carried out among workers from an open-cast iron ore mine in South
      Goa with an objective to assess morbidity among these workers. Investigations
      were carried out at the Occupational Health Service Clinic of the mining company.
      Nearly 0.6% workers had pneumoconiosis, 3.2% had abnormal spirometry findings,
      38.16% had hearing loss and 27.7% had defective vision respectively. The
      prevalence of other chronic diseases were as follows: diabetes 5.1%, hypertension
      8.3%, dyslipidemia 37.5% and polycythemia 12.7% respectively. Since the findings
      were not compared with the pre-placement records and as most of the workers are
      young with duration of exposures <10 years, relationship cannot be definitely
      determined. The study findings are suggesting an association between the
      occupation in mining with pneumoconiosis, compromised lung function and hearing
      loss. However for the other finding further analytical studies are required to
      see for any association. Airborne respirable dust survey and noise monitoring
      studies also need to be carried out. 

PMID- 24748361
TI  - Seroprevalence of transfusion transmissible infections among blood donors at the
      blood bank of a Medical College of Kolkata.
AB  - Seroprevalence of transfusion transmissible infections (TTIs) among blood donors
      can be used to monitor the prevalence among apparently healthy adult population.
      The present study was conducted to determine the profile of blood donors and
      seroprevalence of TTI among them. Retrospective analysis of the donors of a blood
      bank attached with a tertiary care hospital of Kolkata in 2011 was carried out.
      Data were analyzed with SPSS version 17. Majority (85%) of the donors were male,
      two-third in the age group of 21-40 years. Among the donors 2.79% were positive
      for any of the screened TTIs. Seroprevalence was highest for hepatitis B (1.41%)
      followed by human immunodeficiency virus (0.60%) and hepatitis C (0.59%) and
      least for syphilis (0.23%). Seropositivity increased with age up to 50 years.
      There was no significant difference in seropositivity between male and female.
      Highly sensitive donor screening and public awareness program can make
      transfusion of blood products safe. 

PMID- 24748362
TI  - Community based monitoring under national rural health mission in Maharashtra:
      status at primary health centers.
AB  - This study compares the implementation of community-based monitoring (CBM) in 45
      primary health centers (PHCs) in the pilot phase in Maharashtra with the equal
      number of randomly selected PHCs not implementing CBM (non-CBM) from the same
      districts. Information was collected by teams from Community Medicine Departments
      by visiting selected PHCs. Establishment of monitoring committees and training of
      medical officers (MOs) had been completed as required but only 36.36% MOs were
      trained. Only 43.18% MOs received the facility report card. Most of the MOs
      (90.90%) attended Jansunwai and opined that it had increased community awareness
      and the barriers between the people and PHC staff were broken. There was no
      difference in fund utilization and meetings of Rugna Kalyan Samittees. Percentage
      of Institutional deliveries and women receiving Janani Suraksha Yojana benefits
      among home deliveries was more in the non-CBM group of PHCs. 

PMID- 24748363
TI  - Low birth weight among newborns and maternal poor periodontal status.

PMID- 24748364
TI  - Interactions of endoplasmic reticulum and mitochondria Ca(2+) stores with
      capacitative calcium entry.
AB  - Thiamine dependent enzymes are diminished in Alzheimer's disease (AD). Thiamine
      deficiency in vitro and in rodents is a useful model of this reduction. Thiamine
      interacts with cellular calcium stores. To directly test the relevance of the
      thiamine dependent changes to dynamic processes in AD, the interactions must be
      studied in cells from patients with AD. These studies employed fibroblasts.
      Mitochondrial dysfunction including reductions in thiamine dependent enzymes and
      abnormalities in calcium homeostasis and oxidative processes occur in fibroblasts
      from Alzheimer's Disease (AD) patients. Bombesin-releasable calcium stores (BRCS)
      from the endoplasmic reticulum (ER) are exaggerated in fibroblasts from patients
      with AD bearing a presenilin-1 (PS-1) mutation and in control fibroblasts treated
      with oxidants. ER calcium regulates calcium entry into the cell through
      capacitative calcium entry (CCE), which is reduced in fibroblasts and neurons
      from mice bearing PS-1 mutations. Under physiological conditions, mitochondria
      and ER play important and interactive roles in the regulation of Ca(2+)
      homeostasis. Thus, the interactions of mitochondria and oxidants with CCE were
      tested. Inhibition of ER Ca(2+)-ATPase by cyclopiazonic acid (CPA) stimulates
      CCE. CPA-induced CCE was diminished by inhibition of mitochondrial Ca(2+) export
      (-60%) or import (-40%). Different aspects of mitochondrial Ca(2+) coupled to CPA
      induced-CCE were sensitive to select oxidants. The effects were very different
      when CCE was examined in the presence of InsP3, a physiological regulator of ER
      calcium release, and subsequent CCE. CCE under these conditions was only mildly
      reduced (20-25%) by inhibition of mitochondrial Ca(2+) export, and inhibition of
      mitochondrial Ca(2+) uptake exaggerated CCE (+53%). However, t-BHP reversed both
      abnormalities. The results suggest that in the presence of InsP3, mitochondria
      buffer the local Ca(2+) released from ER following rapid activation of InsP3R and
      serve as a negative feedback to the CCE. The results suggest that mitochondrial
      Ca(2+) modifies the depletion and refilling mechanism of ER Ca(2+) stores.

PMID- 24748365
TI  - Role of social factors on cell death, cerebral plasticity and recovery after
      stroke.
AB  - Stroke is a serious global health care problem. It is now is the fourth leading
      cause of death and the primary cause of adult disability in the United States.
      Substantial evidence from both experimental and clinical studies has demonstrated
      that social isolation (SI) can increase stroke incidence and impair recovery.
      Epidemiological studies demonstrate that an increasing number of patients are
      living alone, and as the aging population increases, loneliness will only
      increase in prevalence. SI is increasingly identified as an independent risk
      factor for all-cause mortality. In contrast, individuals with high levels of
      social support exhibit more rapid and extensive functional and cognitive recovery
      after a wide variety of pathological insults, including stroke. Clinical data
      suggests that SI is an important risk factor for increased mortality and delayed
      functional recovery following ischemic stroke. Attesting to the importance of
      mortality and behavioral factors in stroke outcome is that these same effects can
      be reproduced in animal models of experimental stroke. This has allowed
      researchers to identify several mechanistic changes that occur with affiliative
      interactions. These include decreased systemic inflammation, elaboration of
      growth factors including brain derived neurotropic factor (BDNF), enhanced
      neurogenesis, and improved neuroimmune responsiveness in group housed animals.
      These may mediate the beneficial effects of social interaction on improving
      stroke recovery and reducing neuronal death. In this review we provide an
      overview of the effects of SI on ischemic injury and recovery and discuss their
      clinical and therapeutic implications. 

PMID- 24748366
TI  - Unmet needs in squamous cell carcinoma of the lung: potential role for
      immunotherapy.
AB  - Squamous cell carcinoma of the lung accounts for 20-30% of non-small cell lung
      cancers (NSCLC). Despite the differences in disease characteristics between
      squamous and non-squamous NSCLC, both have historically been treated similarly in
      the clinic. Recently approved drugs have revealed differences in activity and
      safety profiles across histologic subtypes and have applicability in treating non
      squamous, but not typically squamous, NSCLC. Exploration of immune checkpoints-
      co-inhibitory molecules used to regulate immune responses--has resulted in novel
      immunotherapies designed to interrupt signaling through the cytotoxic T
      lymphocyte-associated antigen-4 or programmed cell death protein-1 pathways on
      lymphocytes. Modulation of these pathways can lead to restored antitumor immune
      responses, and preliminary evidence shows that agents targeting these pathways
      have activity in lung cancer, including squamous NSCLC.

PMID- 24748367
TI  - Chronic exposure to low doses of HgCl2 avoids calcium handling impairment in the
      right ventricle after myocardial infarction in rats.
AB  - Right ventricle systolic dysfunction is a major risk factor for death and heart
      failure after myocardial infarction (MI). Heavy metal exposure has been
      associated with the development of several cardiovascular diseases, such as MI.
      The aim of this study was to investigate whether chronic exposure to low doses of
      mercury chloride (HgCl2) enhances the functional deterioration of right ventricle
      strips after MI. Male Wistar rats were divided into four groups: Control
      (vehicle); HgCl2 (exposure during 4 weeks- 1st dose 4.6 ug/kg, subsequent dose
      0.07 ug/kg/day, i.m. to cover daily loss); MI surgery induced and HgCl2-MI
      groups. One week after MI, the morphological and hemodynamic measurements and
      isometric tension of right ventricle strips were investigated. The chronic HgCl2
      exposure did not worsen the injury compared with MI alone in the morphological or
      hemodynamic parameters evaluated. At basal conditions, despite similar maximum
      isometric force at L-max, relaxation time was increased in the MI group but
      unaffected in the HgCl2-MI compared to the Control group. Impairment of the
      sarcoplasmic reticulum (SR) function and reduction in the sarcolemmal calcium
      influx were observed in MI group associated with SERCA2a reduction and increased
      PLB protein expression. Induction of MI in chronic HgCl2 exposed rats did not
      cause any alteration in the developed force at L-max, lusitropic function or 
      dF/dt except for a tendency of a reduction SR function. These findings could be
      partially explained by the normalization in the sarcolemmal calcium influx and
      the increase in NCX protein expression observed only in this group. These results
      suggest that chronic exposure to low doses of HgCl2 prevents the impaired SR
      function and the reduced sarcolemmal calcium influx observed in MI likely by
      acting on NCX, PLB and SERCA2a protein expression. 

PMID- 24748370
TI  - Response to: The interpretability of doctor identification badges in UK
      hospitals: a survey of nurses and patients' by Hickerton et al.

PMID- 24748369
TI  - Distribution, potential source and ecotoxicological risk of polychlorinated
      biphenyls and polybrominated diphenyl ethers in the surface water of the Three
      Gorges Dam region of the Yangtze River, China.
AB  - Distributions, potential sources and ecotoxicological risks of PCBs and PBDEs in
      surface water of the Three Gorges Dam (TGD) region (Yangtze River, China) were
      investigated. Samples were collected from 18 sites from upstream (UTGD) and
      downstream (DTGD) of the TGD. Thirty-two PCBs and ten PBDEs were analyzed.
      SigmaPCBs from the UTGD and DTGD ranged from 10.6 to 26.1 and 1.7 to 29.8 ng L(
      1), respectively. SigmaPBDEs from the UTGD and DTGD ranged from 2.0 to 17.6 and
      0.8 to 11.1 ng L(-1), respectively. The total concentrations of PCBs and PBDEs
      showed a declining trend from the UTGD to DTGD. Independent-samples t test
      analysis showed no statistical significance of SigmaPCBs and SigmaPBDEs between
      the UTGD and DTGD samples. Principal component analysis indicated the difference
      of potential sources and levels of PCBs and PBDEs in the study area. The
      potential eco-toxicological risk of PCBs in surface water of the TGD region is
      very low, whereas special attention needs to be paid to PBDEs in the study area.

PMID- 24748368
TI  - Causes of non-malarial fever in Laos: a prospective study.
AB  - BACKGROUND: Because of reductions in the incidence of Plasmodium falciparum
      malaria in Laos, identification of the causes of fever in people without malaria,
      and discussion of the best empirical treatment options, are urgently needed. We
      aimed to identify the causes of non-malarial acute fever in patients in rural
      Laos. METHODS: For this prospective study, we recruited 1938 febrile patients,
      between May, 2008, and December, 2010, at Luang Namtha provincial hospital in
      northwest Laos (n=1390), and between September, 2008, and December, 2010, at
      Salavan provincial hospital in southern Laos (n=548). Eligible participants were
      aged 5-49 years with fever (>=38 degrees C) lasting 8 days or less and were
      eligible for malaria testing by national guidelines. FINDINGS: With conservative
      definitions of cause, we assigned 799 (41%) patients a diagnosis. With exclusion
      of influenza, the top five diagnoses when only one aetiological agent per patient
      was identified were dengue (156 [8%] of 1927 patients), scrub typhus (122 [7%] of
      1871), Japanese encephalitis virus (112 [6%] of 1924), leptospirosis (109 [6%] of
      1934), and bacteraemia (43 [2%] of 1938). 115 (32%) of 358 patients at Luang
      Namtha hospital tested influenza PCR-positive between June and December, 2010, of
      which influenza B was the most frequently detected strain (n=121 [87%]). Disease
      frequency differed significantly between the two sites: Japanese encephalitis
      virus infection (p=0.04), typhoid (p=0.006), and leptospirosis (p=0.001) were
      more common at Luang Namtha, whereas dengue and malaria were more common at
      Salavan (all p<0.0001). With use of evidence from southeast Asia when possible,
      we estimated that azithromycin, doxycycline, ceftriaxone, and ofloxacin would
      have had significant efficacy for 258 (13%), 240 (12%), 154 (8%), and 41 (2%) of
      patients, respectively. INTERPRETATION: Our findings suggest that a wide range of
      treatable or preventable pathogens are implicated in non-malarial febrile illness
      in Laos. Empirical treatment with doxycycline for patients with undifferentiated
      fever and negative rapid diagnostic tests for malaria and dengue could be an
      appropriate strategy for rural health workers in Laos. FUNDING: Wellcome Trust,
      WHO-Western Pacific Region, Foundation for Innovative New Diagnostics, US Centers
      for Disease Control and Prevention

PMID- 24748371
TI  - The use of report cards and outcome measurements to improve the safety of
      surgical care: the American College of Surgeons National Surgical Quality
      Improvement Program.
AB  - Postoperative adverse events occur all too commonly and contribute greatly to our
      large and increasing healthcare costs. Surgeons, as well as hospitals, need to
      know their own outcomes in order to recognise areas that need improvement before
      they can work towards reducing complications. In the USA, the American College of
      Surgeons National Surgical Quality Improvement Project (ACS NSQIP) collects
      clinical data that provide benchmarks for providers and hospitals. This review
      summarises the history of ACS NSQIP and its components, and describes the
      evidence that feeding outcomes back to providers, along with real-time
      comparisons with other hospital rates, leads to quality improvement, better
      patient outcomes, cost savings and overall improved patient safety. The potential
      harms and limitations of the program are discussed. 

PMID- 24748372
TI  - Tweets about hospital quality: a mixed methods study.
AB  - BACKGROUND: Twitter is increasingly being used by patients to comment on their
      experience of healthcare. This may provide information for understanding the
      quality of healthcare providers and improving services. OBJECTIVE: To examine
      whether tweets sent to hospitals in the English National Health Service contain
      information about quality of care. To compare sentiment on Twitter about
      hospitals with established survey measures of patient experience and standardised
      mortality rates. DESIGN: A mixed methods study including a quantitative analysis
      of all 198,499 tweets sent to English hospitals over a year and a qualitative
      directed content analysis of 1000 random tweets. Twitter sentiment and
      conventional quality metrics were compared using Spearman's rank correlation
      coefficient. KEY RESULTS: 11% of tweets to hospitals contained information about
      care quality, with the most frequent topic being patient experience (8%).
      Comments on effectiveness or safety of care were present, but less common (3%).
      77% of tweets about care quality were positive in tone. Other topics mentioned in
      tweets included messages of support to patients, fundraising activity, self
      promotion and dissemination of health information. No associations were observed
      between Twitter sentiment and conventional quality metrics. CONCLUSIONS: Only a
      small proportion of tweets directed at hospitals discuss quality of care and
      there was no clear relationship between Twitter sentiment and other measures of
      quality, potentially limiting Twitter as a medium for quality monitoring.
      However, tweets did contain information useful to target quality improvement
      activity. Recent enthusiasm by policy makers to use social media as a quality
      monitoring and improvement tool needs to be carefully considered and subjected to
      formal evaluation.

PMID- 24748373
TI  - Impact of genomics on the field of probiotic research: historical perspectives to
      modern paradigms.
AB  - For thousands of years, humans have safely consumed microorganisms through
      fermented foods. Many of these bacteria are considered probiotics, which act
      through diverse mechanisms to confer a health benefit to the host. However, it
      was not until the availability of whole-genome sequencing and the era of genomics
      that mechanisms of probiotic efficacy could be discovered. In this review, we
      explore the history of the probiotic concept and the current standard of
      integrated genomic techniques to discern the complex, beneficial relationships
      between probiotic microbes and their hosts. 

PMID- 24748374
TI  - Development of a robust and sensitive pyrosequencing assay for the detection of
      IDH1/2 mutations in gliomas.
AB  - Assessment of the mutational status of the isocitrate dehydrogenase 1/2 (IDH1/2)
      gene has become an integral part of the standard diagnostic procedure and,
      therefore, needs to be accurate. This may, however, be compromised by various
      factors including the method of analysis and a low tumor cell content. We have
      developed a rapid, sensitive and robust assay to detect all types of mutation in
      either IDH1 or IDH2 using pyrosequencing. The efficacy of detecting mutation was
      evaluated using a panel of control plasmids representing all the different types
      of IDH1/2 mutation and a set of 160 tumor specimens. The sensitivity of the
      assays was examined by a serial dilution analysis performed on samples containing
      various ratios of wild-type and mutant alleles. The pyrosequencing assay detected
      as little as 5 % of mutant alleles for most mutation types, while conventional
      Sanger sequencing required the presence of at least 20 % of mutant alleles for
      identifying mutations. The pyrosequencing assay detected IDH1/2 mutations in
      three samples which were missed by Sanger sequencing due to their low tumor cell
      contents. Our assay is particularly useful for the analysis of a large number of
      specimens as in a retrospective clinical study for example.

PMID- 24748375
TI  - Temperature gradient measurements by using thermoelectric effect in CNTs-silicone
      adhesive composite.
AB  - This work presents the fabrication and investigation of thermoelectric cells
      based on composite of carbon nanotubes (CNT) and silicone adhesive. The composite
      contains CNT and silicon adhesive 1?1 by weight. The current-voltage
      characteristics and dependences of voltage, current and Seebeck coefficient on
      the temperature gradient of cell were studied. It was observed that with increase
      in temperature gradient the open circuit voltage, short circuit current and the
      Seebeck coefficient of the cells increase. Approximately 7 times increase in
      temperature gradient increases the open circuit voltage and short circuit current
      up to 40 and 5 times, respectively. The simulation of experimental results is
      also carried out; the simulated results are well matched with experimental
      results. 

PMID- 24748376
TI  - Soluble extract from Moringa oleifera leaves with a new anticancer activity.
AB  - Moringa oleifera has been regarded as a food substance since ancient times and
      has also been used as a treatment for many diseases. Recently, various
      therapeutic effects of M. oleifera such as antimicrobial, anticancer, anti
      inflammatory, antidiabetic, and antioxidant effects have been investigated;
      however, most of these studies described only simple biological phenomena and
      their chemical compositions. Due to the increasing attention on natural products,
      such as those from plants, and the advantages of oral administration of
      anticancer drugs, soluble extracts from M. oleifera leaves (MOL) have been
      prepared and their potential as new anticancer drug candidates has been assessed
      in this study. Here, the soluble cold Distilled Water extract (4 degrees C;
      concentration, 300 ug/mL) from MOL greatly induced apoptosis, inhibited tumor
      cell growth, and lowered the level of internal reactive oxygen species (ROS) in
      human lung cancer cells as well as other several types of cancer cells,
      suggesting that the treatment of cancer cells with MOL significantly reduced
      cancer cell proliferation and invasion. Moreover, over 90% of the genes tested
      were unexpectedly downregulated more than 2-fold, while just below 1% of the
      genes were upregulated more than 2-fold in MOL extract-treated cells, when
      compared with nontreated cells. Since severe dose-dependent rRNA degradation was
      observed, the abnormal downregulation of numerous genes was considered to be
      attributable to abnormal RNA formation caused by treatment with MOL extracts.
      Additionally, the MOL extract showed greater cytotoxicity for tumor cells than
      for normal cells, strongly suggesting that it could potentially be an ideal
      anticancer therapeutic candidate specific to cancer cells. These results suggest
      the potential therapeutic implications of the soluble extract from MOL in the
      treatment of various types of cancers. 

PMID- 24748377
TI  - Pathway-specific engineered mouse allograft models functionally recapitulate
      human serous epithelial ovarian cancer.
AB  - The high mortality rate from ovarian cancers can be attributed to late-stage
      diagnosis and lack of effective treatment. Despite enormous effort to develop
      better targeted therapies, platinum-based chemotherapy still remains the standard
      of care for ovarian cancer patients, and resistance occurs at a high rate. One of
      the rate limiting factors for translation of new drug discoveries into clinical
      treatments has been the lack of suitable preclinical cancer models with high
      predictive value. We previously generated genetically engineered mouse (GEM)
      models based on perturbation of Tp53 and Rb with or without Brca1 or Brca2 that
      develop serous epithelial ovarian cancer (SEOC) closely resembling the human
      disease on histologic and molecular levels. Here, we describe an adaptation of
      these GEM models to orthotopic allografts that uniformly develop tumors with
      short latency and are ideally suited for routine preclinical studies. Ovarian
      tumors deficient in Brca1 respond to treatment with cisplatin and olaparib, a
      PARP inhibitor, whereas Brca1-wild type tumors are non-responsive to treatment,
      recapitulating the relative sensitivities observed in patients. These mouse
      models provide the opportunity for evaluation of effective therapeutics,
      including prediction of differential responses in Brca1-wild type and Brca1
      deficient tumors and development of relevant biomarkers. 

PMID- 24748378
TI  - A robust classifier to distinguish noise from fMRI independent components.
AB  - Analyzing Functional Magnetic Resonance Imaging (fMRI) of resting brains to
      determine the spatial location and activity of intrinsic brain networks--a novel
      and burgeoning research field--is limited by the lack of ground truth and the
      tendency of analyses to overfit the data. Independent Component Analysis (ICA) is
      commonly used to separate the data into signal and Gaussian noise components, and
      then map these components on to spatial networks. Identifying noise from this
      data, however, is a tedious process that has proven hard to automate,
      particularly when data from different institutions, subjects, and scanners is
      used. Here we present an automated method to delineate noisy independent
      components in ICA using a data-driven infrastructure that queries a database of
      246 spatial and temporal features to discover a computational signature of
      different types of noise. We evaluated the performance of our method to detect
      noisy components from healthy control fMRI (sensitivity = 0.91, specificity =
      0.82, cross validation accuracy (CVA) = 0.87, area under the curve (AUC) = 0.93),
      and demonstrate its generalizability by showing equivalent performance on (1) an
      age- and scanner-matched cohort of schizophrenia patients from the same
      institution (sensitivity = 0.89, specificity = 0.83, CVA = 0.86), (2) an age
      matched cohort on an equivalent scanner from a different institution (sensitivity
      = 0.88, specificity = 0.88, CVA = 0.88), and (3) an age-matched cohort on a
      different scanner from a different institution (sensitivity = 0.72, specificity =
      0.92, CVA = 0.79). We additionally compare our approach with a recently published
      method. Our results suggest that our method is robust to noise variations due to
      population as well as scanner differences, thereby making it well suited to the
      goal of automatically distinguishing noise from functional networks to enable
      investigation of human brain function.

PMID- 24748379
TI  - Genetic analysis of the Gdh and Bg genes of animal-derived Giardia duodenalis
      isolates in Northeastern China and evaluation of zoonotic transmission potential.
AB  - BACKGROUND: Giardia duodenalis is a common intestinal parasite that infects
      humans and many other mammals, mainly distributing in some areas with poor
      sanitation. The proportion of the human giardiasis burden attributable to G.
      duodenalis of animal origin differs in different geographical areas. In Mainland
      China, genetic data of the gdh and bg genes of G. duodenalis from animals are
      only limited in dogs and cats. The aim of the study was to provide information on
      the genetic characterizations of animal-derived G. duodenalis isolates (from
      rabbits, sheep and cattle) at both loci in Heilongjiang Province, Northeastern
      China, and to assess the potential for zoonotic transmission.
      METHODOLOGY/PRINCIPAL FINDINGS: 61 G. duodenalis isolates from animal feces
      (dairy and beef cattle, sheep and rabbits) in Heilongjiang Province were
      characterized at the gdh and bg loci in the present study. The gdh and bg gene
      sequences of sheep-derived G. duodenalis assemblage AI, and the gdh sequences of
      rabbit-derived G. duodenalis assemblage B had 100% similarity with those from
      humans, respectively. Novel subtypes of G. duodenalis were identified, with one
      and seven subtypes for assemblages A and E at the gdh locus, and two and three
      subtypes for assemblages B and E at the bg locus, respectively. Three pairs of
      the same bg sequences of assemblage E were observed in sheep and cattle.
      CONCLUSIONS/SIGNIFICANCE: This is the first description of genetic
      characterizations of the gdh and bg genes of G. duodenalis from rabbits, sheep
      and cattle in Mainland China. Homology analysis of assemblages AI and B implied
      the possibility of zoonotic transmission. The novel subtypes of assemblages of G.
      duodenalis may represent the endemic genetic characteristics of G. duodenalis in
      Heilongjiang Province, China.

PMID- 24748381
TI  - Lateral sphenoid sinus recess cerebrospinal fluid leak: a case series.
AB  - The lateral recess of the sphenoid sinus is one of the most common sites of
      meningocele and spontaneous cerebrospinal fluid (CSF) leak. Despite the
      availability of several techniques for closure of skull base defects occurring in
      this location, recurrence still poses a major challenge. This report reviews the
      experience of surgical repair of lateral sphenoid sinus recess CSF leak at a
      tertiary referral center and provides a brief discussion of this rare lesion.
      Nine surgeries were performed for six cases of spontaneous lateral sphenoid sinus
      recess CSF leak (two revisions and one repair of a new defect). Two patients
      presented with intracranial hypertension (ICH) and four with meningocele or
      meningoencephalocele. The transpterygoid approach was used in two procedures. A
      multilayer graft was used in seven cases and a nasoseptal flap in two. Three
      patients received lumbar or ventricular shunts, and one received acetazolamide
      for ICH management. Two minor complications were recorded, and the overall
      surgical success rate was 78 %. We conclude that nasoseptal flaps are a valid
      option for repair of recurrent CSF leaks, particularly in the lateral sphenoid
      sinus recess. Furthermore, identification and correction of ICH plays an
      essential role in the success of treatment in this patient population.

PMID- 24748380
TI  - Quantitative proteomic analysis of oral brush biopsies identifies secretory
      leukocyte protease inhibitor as a promising, mechanism-based oral cancer
      biomarker.
AB  - A decrease in the almost fifty percent mortality rate from oral cancer is needed
      urgently. Improvements in early diagnosis and more effective preventive
      treatments could affect such a decrease. Towards this end, we undertook for the
      first time an in-depth mass spectrometry-based quantitative shotgun proteomics
      study of non-invasively collected oral brush biopsies. Proteins isolated from
      brush biopsies from healthy normal tissue, oral premalignant lesion tissue
      (OPMLs), oral squamous cell carcinoma (OSCC) and matched control tissue were
      compared. In replicated proteomic datasets, the secretory leukocyte protease
      inhibitor (SLPI) protein stood out based on its decrease in abundance in both
      OPML and OSCC lesion tissues compared to healthy normal tissue. Western blotting
      in additional brushed biopsy samples confirmed a trend of gradual decreasing SLPI
      abundance between healthy normal and OPML tissue, with a larger decrease in OSCC
      lesion tissue. A similar SLPI decrease was observed in-vitro comparing model OPML
      and OSCC cell lines. In addition, exfoliated oral cells in patients' whole saliva
      showed a loss of SLPI correlated with oral cancer progression. These results,
      combined with proteomics data indicating a decrease in SLPI in matched healthy
      control tissue from OSCC patients compared to tissue from healthy normal tissue,
      suggested a systemic decrease of SLPI in oral cells correlated with oral cancer
      development. Finally, in-vitro experiments showed that treatment with SLPI
      significantly decreased NF-kB activity in an OPML cell line. The findings
      indicate anti-inflammatory activity in OPML, supporting a mechanistic role of
      SLPI in OSCC progression and suggesting its potential for preventative treatment
      of at-risk oral lesions. Collectively, our results show for the first time the
      potential for SLPI as a mechanism-based, non-invasive biomarker of oral cancer
      progression with potential in preventive treatment. 

PMID- 24748382
TI  - Soil moisture and excavation behaviour in the Chaco leaf-cutting ant (Atta
      vollenweideri): digging performance and prevention of water inflow into the nest.
AB  - The Chaco leaf-cutting ant Atta vollenweideri is native to the clay-heavy soils
      of the Gran Chaco region in South America. Because of seasonal floods, colonies
      are regularly exposed to varying moisture across the soil profile, a factor that
      not only strongly influences workers' digging performance during nest building,
      but also determines the suitability of the soil for the rearing of the colony's
      symbiotic fungus. In this study, we investigated the effects of varying soil
      moisture on behaviours associated with underground nest building in A.
      vollenweideri. This was done in a series of laboratory experiments using
      standardised, plastic clay-water mixtures with gravimetric water contents ranging
      from relatively brittle material to mixtures close to the liquid limit. Our
      experiments showed that preference and group-level digging rate increased with
      increasing water content, but then dropped considerably for extremely moist
      materials. The production of vibrational recruitment signals during digging
      showed, on the contrary, a slightly negative linear correlation with soil
      moisture. Workers formed and carried clay pellets at higher rates in moist clay,
      even at the highest water content tested. Hence, their weak preference and low
      group-level excavation rate observed for that mixture cannot be explained by any
      inability to work with the material. More likely, extremely high moistures may
      indicate locations unsuitable for nest building. To test this hypothesis, we
      simulated a situation in which workers excavated an upward tunnel below
      accumulated surface water. The ants stopped digging about 12 mm below the
      interface soil/water, a behaviour representing a possible adaptation to the
      threat of water inflow field colonies are exposed to while digging under
      seasonally flooded soils. Possible roles of soil water in the temporal and
      spatial pattern of nest growth are discussed. 

PMID- 24748383
TI  - Characterization of an archaeal two-component system that regulates
      methanogenesis in Methanosaeta harundinacea.
AB  - Two-component signal transduction systems (TCSs) are a major mechanism used by
      bacteria in response to environmental changes. Although many sequenced archaeal
      genomes encode TCSs, they remain poorly understood. Previously, we reported that
      a methanogenic archaeon, Methanosaeta harundinacea, encodes FilI, which
      synthesizes carboxyl-acyl homoserine lactones, to regulate transitions of
      cellular morphology and carbon metabolic fluxes. Here, we report that filI, the
      cotranscribed filR2, and the adjacent filR1 constitute an archaeal TCS. FilI
      possesses a cytoplasmic kinase domain (histidine kinase A and histidine kinase
      like ATPase) and its cognate response regulator. FilR1 carries a receiver (REC)
      domain coupled with an ArsR-related domain with potential DNA-binding ability,
      while FilR2 carries only a REC domain. In a phosphorelay assay, FilI was
      autophosphorylated and specifically transferred the phosphoryl group to FilR1 and
      FilR2, confirming that the three formed a cognate TCS. Through chromatin
      immunoprecipitation-quantitative polymerase chain reaction (ChIP-qPCR) using an
      anti-FilR1 antibody, FilR1 was shown to form in vivo associations with its own
      promoter and the promoter of the filI-filR2 operon, demonstrating a regulatory
      pattern common among TCSs. ChIP-qPCR also detected FilR1 associations with key
      genes involved in acetoclastic methanogenesis, acs4 and acs1. Electrophoretic
      mobility shift assays confirmed the in vitro tight binding of FilR1 to its own
      promoter and those of filI-filR2, acs4, and mtrABC. This also proves the DNA
      binding ability of the ArsR-related domain, which is found primarily in Archaea.
      The archaeal promoters of acs4, filI, acs1, and mtrABC also initiated FilR1
      modulated expression in an Escherichia coli lux reporter system, suggesting that
      FilR1 can up-regulate both archaeal and bacterial transcription. In conclusion,
      this work identifies an archaeal FilI/FilRs TCS that regulates the methanogenesis
      of M. harundinacea. 

PMID- 24748384
TI  - Genotyping-by-sequencing for Populus population genomics: an assessment of genome
      sampling patterns and filtering approaches.
AB  - Continuing advances in nucleotide sequencing technology are inspiring a suite of
      genomic approaches in studies of natural populations. Researchers are faced with
      data management and analytical scales that are increasing by orders of magnitude.
      With such dramatic advances comes a need to understand biases and error rates,
      which can be propagated and magnified in large-scale data acquisition and
      processing. Here we assess genomic sampling biases and the effects of various
      population-level data filtering strategies in a genotyping-by-sequencing (GBS)
      protocol. We focus on data from two species of Populus, because this genus has a
      relatively small genome and is emerging as a target for population genomic
      studies. We estimate the proportions and patterns of genomic sampling by
      examining the Populus trichocarpa genome (Nisqually-1), and demonstrate a
      pronounced bias towards coding regions when using the methylation-sensitive ApeKI
      restriction enzyme in this species. Using population-level data from a closely
      related species (P. tremuloides), we also investigate various approaches for
      filtering GBS data to retain high-depth, informative SNPs that can be used for
      population genetic analyses. We find a data filter that includes the designation
      of ambiguous alleles resulted in metrics of population structure and Hardy
      Weinberg equilibrium that were most consistent with previous studies of the same
      populations based on other genetic markers. Analyses of the filtered data (27,910
      SNPs) also resulted in patterns of heterozygosity and population structure
      similar to a previous study using microsatellites. Our application demonstrates
      that technically and analytically simple approaches can readily be developed for
      population genomics of natural populations. 

PMID- 24748385
TI  - Performance analysis of electronic structure codes on HPC systems: a case study
      of SIESTA.
AB  - We report on scaling and timing tests of the SIESTA electronic structure code for
      ab initio molecular dynamics simulations using density-functional theory. The
      tests are performed on six large-scale supercomputers belonging to the PRACE Tier
      0 network with four different architectures: Cray XE6, IBM BlueGene/Q, BullX, and
      IBM iDataPlex. We employ a systematic strategy for simultaneously testing weak
      and strong scaling, and propose a measure which is independent of the range of
      number of cores on which the tests are performed to quantify strong scaling
      efficiency as a function of simulation size. We find an increase in efficiency
      with simulation size for all machines, with a qualitatively different curve
      depending on the supercomputer topology, and discuss the connection of this
      functional form with weak scaling behaviour. We also analyze the absolute timings
      obtained in our tests, showing the range of system sizes and cores favourable for
      different machines. Our results can be employed as a guide both for running
      SIESTA on parallel architectures, and for executing similar scaling tests of
      other electronic structure codes. 

PMID- 24748386
TI  - Novel antimicrobial peptides that inhibit gram positive bacterial exotoxin
      synthesis.
AB  - Gram-positive bacteria, such as Staphylococcus aureus, cause serious human
      illnesses through combinations of surface virulence factors and secretion of
      exotoxins. Our prior studies using the protein synthesis inhibitor clindamycin
      and signal transduction inhibitors glycerol monolaurate and alpha-globin and beta
      globin chains of hemoglobin indicate that their abilities to inhibit exotoxin
      production by S. aureus are separable from abilities to inhibit growth of the
      organism. Additionally, our previous studies suggest that inhibition of exotoxin
      production, in absence of ability to kill S. aureus and normal flora
      lactobacilli, will prevent colonization by pathogenic S. aureus, while not
      interfering with lactobacilli colonization. These disparate activities may be
      important in development of novel anti-infective agents that do not alter normal
      flora. We initiated studies to explore the exotoxin-synthesis-inhibition activity
      of hemoglobin peptides further to develop potential agents to prevent S. aureus
      infections. We tested synthesized alpha-globin chain peptides, synthetic variants
      of alpha-globin chain peptides, and two human defensins for ability to inhibit
      exotoxin production without significantly inhibiting S. aureus growth. All of
      these peptides were weakly or not inhibitory to bacterial growth. However, the
      peptides were inhibitory to exotoxin production with increasing activity
      dependent on increasing numbers of positively-charged amino acids. Additionally,
      the peptides could be immobilized on agarose beads or have amino acid sequences
      scrambled and still retain exotoxin-synthesis-inhibition. The peptides are not
      toxic to human vaginal epithelial cells and do not inhibit growth of normal flora
      L. crispatus. These peptides may interfere with plasma membrane signal
      transduction in S. aureus due to their positive charges. 

PMID- 24748387
TI  - Surrogate production of eggs and sperm by intrapapillary transplantation of germ
      cells in cytoablated adult fish.
AB  - Germ cell transplantation (GCT) is a promising assisted reproductive technology
      for the conservation and propagation of endangered and valuable genetic
      resources. In teleost fish, GCT in adult gonads has been achieved only in male
      recipients, limiting greatly the usefulness of this technique in situations where
      both sexes need equal and timely attention for conservation and/or propagation.
      Here we describe a simplified GCT approach that ultimately leads to production of
      donor-derived eggs and sperm in considerably short time. Donor germ cells
      isolated from young pejerrey Odontesthes bonariensis (Atherinopsidae) were
      transplanted non-surgically through the genital papilla into the sexually mature
      gonads of Patagonian pejerrey O. hatcheri recipients whose gonads have been
      depleted of endogenous GCs by heat (26 degrees C) and chemical treatment (four
      doses of Busulfan at 30 mg/kg and 40 mg/kg for females and males, respectively).
      Transplanted spermatogonial and oogonial cells were able to recolonize the
      recipients' gonads and produce functional donor origin eggs and sperm within 7
      months from the GCT. We confirmed the presence of donor-derived gametes by PCR in
      17% and 5% of the surrogate O. hatcheri fathers and mothers, respectively. The
      crosses between surrogate fathers and O. bonariensis mothers yielded 12.6-39.7%
      pure O. bonariensis and that between a surrogate mother and an O. bonariensis
      father yielded 52.2% pure O. bonariensis offspring. Our findings confirm that
      transplantation of germ cells into sexually competent adult fish by non-surgical
      methods allows the production of functional donor-derived eggs and sperm in a
      considerably short time. The methods described here could play a vital role in
      conservation and rapid propagation of endangered fish genetic resources. 

PMID- 24748389
TI  - Nanoparticle incorporation of melittin reduces sperm and vaginal epithelium
      cytotoxicity.
AB  - Melittin is a cytolytic peptide component of bee venom which rapidly integrates
      into lipid bilayers and forms pores resulting in osmotic lysis. While the
      therapeutic utility of free melittin is limited by its cytotoxicity,
      incorporation of melittin into the lipid shell of a perfluorocarbon nanoparticle
      has been shown to reduce its toxicity in vivo. Our group has previously
      demonstrated that perfluorocarbon nanoparticles containing melittin at
      concentrations <10 uM inhibit HIV infectivity in vitro. In the current study, we
      assessed the impact of blank and melittin-containing perfluorocarbon
      nanoparticles on sperm motility and the viability of both sperm and vaginal
      epithelial cells. We found that free melittin was toxic to sperm and vaginal
      epithelium at concentrations greater than 2 uM (p<0.001). However, melittin
      nanoparticles were not cytotoxic to sperm (p = 0.42) or vaginal epithelium (p =
      0.48) at an equivalent melittin concentration of 10 uM. Thus, nanoparticle
      formulation of melittin reduced melittin cytotoxicity fivefold and prevented
      melittin toxicity at concentrations previously shown to inhibit HIV infectivity.
      Melittin nanoparticles were toxic to vaginal epithelium at equivalent melittin
      concentrations >=20 uM (p<0.001) and were toxic to sperm at equivalent melittin
      concentrations >=40 uM (p<0.001). Sperm cytotoxicity was enhanced by targeting of
      the nanoparticles to the sperm surface antigen sperm adhesion molecule 1. While
      further testing is needed to determine the extent of cytotoxicity in a more
      physiologically relevant model system, these results suggest that melittin
      containing nanoparticles could form the basis of a virucide that is not toxic to
      sperm and vaginal epithelium. This virucide would be beneficial for HIV
      serodiscordant couples seeking to achieve natural pregnancy. 

PMID- 24748388
TI  - Coexistence of low vitamin D and high fibroblast growth factor-23 plasma levels
      predicts an adverse outcome in patients with coronary artery disease.
AB  - OBJECTIVE: Vitamin D and fibroblast growth factor-23 (FGF-23) are related with
      cardiovascular disorders. We have investigated the relationship of calcidiol
      (vitamin D metabolite) and FGF-23 plasma levels with the incidence of adverse
      outcomes in patients with coronary artery disease. METHODS: Prospective follow-up
      study of 704 outpatients, attending the departments of Cardiology of four
      hospitals in Spain, 6-12 months after an acute coronary event. Baseline
      calcidiol, FGF-23, parathormone, and phosphate plasma levels were assessed. The
      outcome was the development of acute ischemic events (any acute coronary
      syndrome, stroke, or transient ischemic attack), heart failure, or death. Cox
      regression adjusted for the main confounders was performed. RESULTS: Calcidiol
      levels showed a moderate-severe decrease in 57.3% of cases. Parathormone, FGF-23,
      and phosphate levels were increased in 30.0%, 11.5% and 0.9% of patients,
      respectively. Only 22.4% of patients had glomerular filtration rate<60 ml/min1.73
      m2. After a mean follow-up was 2.15+/-0.99 years, 77 patients developed the
      outcome. Calcidiol (hazard ratio [HR] = 0.67; 95% confidence interval [CI] = 0.48
      0.94; p = 0.021) and FGF-23 (HR = 1.13; 95% CI = 1.04-1.23; p = 0.005) plasma
      levels predicted independently the outcome. There was a significant interaction
      between calcidiol and FGF-23 levels (p = 0.025). When the population was divided
      according to FGF-23 levels, calcidiol still predicted the outcome independently
      in patients with FGF-23 levels higher than the median (HR = 0.50; 95% CI = 0.31
      0.80; p = 0.003) but not in those with FGF-23 levels below this value (HR = 1.03;
      95% CI = 0.62-1.71; p = 0.904). CONCLUSIONS: Abnormalities in mineral metabolism
      are frequent in patients with stable coronary artery disease. In this population,
      low calcidiol plasma levels predict an adverse prognosis in the presence of high
      FGF-23 levels.

PMID- 24748390
TI  - Infrared spectroscopy of pollen identifies plant species and genus as well as
      environmental conditions.
AB  - BACKGROUND: It is imperative to have reliable and timely methodologies for
      analysis and monitoring of seed plants in order to determine climate-related
      plant processes. Moreover, impact of environment on plant fitness is
      predominantly based on studies of female functions, while the contribution of
      male gametophytes is mostly ignored due to missing data on pollen quality. We
      explored the use of infrared spectroscopy of pollen for an inexpensive and rapid
      characterization of plants. METHODOLOGY: The study was based on measurement of
      pollen samples by two Fourier transform infrared techniques: single reflectance
      attenuated total reflectance and transmission measurement of sample pellets. The
      experimental set, with a total of 813 samples, included five pollination seasons
      and 300 different plant species belonging to all principal spermatophyte clades
      (conifers, monocotyledons, eudicots, and magnoliids). RESULTS: The spectroscopic
      based methodology enables detection of phylogenetic variations, including the
      separation of confamiliar and congeneric species. Furthermore, the methodology
      enables measurement of phenotypic plasticity by the detection of inter-annual
      variations within the populations. The spectral differences related to
      environment and taxonomy are interpreted biochemically, specifically variations
      of pollen lipids, proteins, carbohydrates, and sporopollenins. The study shows
      large variations of absolute content of nutrients for congenital species
      pollinating in the same environmental conditions. Moreover, clear correlation
      between carbohydrate-to-protein ratio and pollination strategy has been detected.
      Infrared spectral database with respect to biochemical variation among the range
      of species, climate and biogeography will significantly improve comprehension of
      plant-environment interactions, including impact of global climate change on
      plant communities.

PMID- 24748391
TI  - Uncovering the protein lysine and arginine methylation network in Arabidopsis
      chloroplasts.
AB  - Post-translational modification of proteins by the addition of methyl groups to
      the side chains of Lys and Arg residues is proposed to play important roles in
      many cellular processes. In plants, identification of non-histone methylproteins
      at a cellular or subcellular scale is still missing. To gain insights into the
      extent of this modification in chloroplasts we used a bioinformatics approach to
      identify protein methyltransferases targeted to plastids and set up a workflow to
      specifically identify Lys and Arg methylated proteins from proteomic data used to
      produce the Arabidopsis chloroplast proteome. With this approach we could
      identify 31 high-confidence Lys and Arg methylation sites from 23 chloroplastic
      proteins, of which only two were previously known to be methylated. These
      methylproteins are split between the stroma, thylakoids and envelope sub
      compartments. They belong to essential metabolic processes, including
      photosynthesis, and to the chloroplast biogenesis and maintenance machinery
      (translation, protein import, division). Also, the in silico identification of
      nine protein methyltransferases that are known or predicted to be targeted to
      plastids provided a foundation to build the enzymes/substrates relationships that
      govern methylation in chloroplasts. Thereby, using in vitro methylation assays
      with chloroplast stroma as a source of methyltransferases we confirmed the
      methylation sites of two targets, plastid ribosomal protein L11 and the beta
      subunit of ATP synthase. Furthermore, a biochemical screening of recombinant
      chloroplastic protein Lys methyltransferases allowed us to identify the enzymes
      involved in the modification of these substrates. The present study provides a
      useful resource to build the methyltransferases/methylproteins network and to
      elucidate the role of protein methylation in chloroplast biology. 

PMID- 24748392
TI  - Global migration and the changing distribution of sickle  haemoglobin: a
      quantitative study of temporal trends  between 1960 and 2000.
AB  - BACKGROUND: Changes in the geographical distribution of genetic disorders are
      often thought to happen slowly, especially when compared with infectious
      diseases. Whereas mutations, genetic drift, and natural selection take place over
      many generations, epidemics can spread through large populations within a few
      days or weeks. Nevertheless, population movements can interfere with these
      processes, and few studies have been done of their eff ect on genetic disorders.
      We aimed to investigate the eff ect of global migration on the distribution of
      the sickle-cell gene-the most common and clinically significant haemoglobin
      structural variant. METHODS: For each country, we extracted data from the World
      Bank's Global Bilateral Migration Database about international human migrations
      between 1960 and 2000. We combined this information with evidence-based estimates
      of national HbS allele frequencies, generated within a Bayesian geostatistical
      framework, to analyse temporal changes in the net numbers of migrants, and
      classified countries with an index summarising these temporal trends. FINDINGS:
      The number of international migrants increased from 92.6 million in 1960, to
      165.2 million in 2000. The estimated global number of migrants with HbS increased
      from about 1.6 million in 1960, to 3.6 million in 2000. This increase was largely
      due to an increase in the number of migrants from countries with HbS allele
      frequencies higher than 10%, from 3.1 million in 1960, to 14.2 million in 2000.
      Additionally, the mean number of countries of origin for each destination country
      increased from 70 (SE 46) in 1960, to 98 (48) in 2000, showing an increasing
      diversity in the network of international migrations between countries. Our index
      of change map shows a patchy distribution of the magnitude of temporal changes,
      with the highest positive and negative values scattered across all continents.
      INTERPRETATION: Global human population movements have had a substantial eff ect
      on the distribution of the HbS gene. Population movements can create a long-term
      burden on health-care systems. Our findings, which emphasise countries in which
      migration fluxes are changing the most, should increase awareness about the
      global burden of haemoglobinopathies and encourage policy makers to implement
      specific public health interventions, such as screening programmes and genetic
      counselling. FUNDING: Wellcome Trust, European Research Council, Bill & Melinda
      Gates Foundation, National Institute of Allergy and Infectious Diseases-National
      Institutes of Health, the Research and Policy for Infectious Disease Dynamics
      program, Fogarty International Center.

PMID- 24748393
TI  - Relative importance of deterministic and stochastic processes in driving
      arbuscular mycorrhizal fungal assemblage during the spreading of a toxic plant.
AB  - Both deterministic and stochastic processes are expected to drive the assemblages
      of arbuscular mycorrhizal (AM) fungi, but little is known about the relative
      importance of these processes during the spreading of toxic plants. Here, the
      species composition and phylogenetic structure of AM fungal communities
      colonizing the roots of a toxic plant, Ligularia virgaurea, and its neighborhood
      plants, were analyzed in patches with different individual densities of L.
      virgaurea (represents the spreading degree). Community compositions of AM fungi
      in both root systems were changed significantly by the L. virgaurea spreading,
      and also these communities fitted the neutral model very well. AM fungal
      communities in patches with absence and presence of L. virgaurea were
      phylogenetically random and clustered, respectively, suggesting that the
      principal ecological process determining AM fungal assemblage shifted from
      stochastic process to environmental filtering when this toxic plant was present.
      Our results indicate that deterministic and stochastic processes together
      determine the assemblage of AM fungi, but the dominant process would be changed
      by the spreading of toxic plants, and suggest that the spreading of toxic plants
      in alpine meadow ecosystems might be involving the mycorrhizal symbionts. 

PMID- 24748394
TI  - IFNL4 ss469415590 variant shows similar performance to rs12979860 as predictor of
      response to treatment against Hepatitis C Virus genotype 1 or 4 in Caucasians.
AB  - OBJECTIVES: The rs12979860 variant, linked to IL28B gene, predicts sustained
      viral response (SVR) to pegylated-interferon/ribavirin (pegIFN/RBV) therapy in
      Hepatitis C Virus genotype 1 or 4 (HCV-1/4)-infected patients. Recently, a
      functional variant, ss469415590, in linkage disequilibrium (LD) with rs12979860,
      has been discovered. Our objective was to assess the value of ss469415590 to
      predict SVR to pegIFN/RBV in Caucasian HCV-1/4-infected individuals and to
      compare its performance with that of rs12979860. METHODS: 272 Caucasian HCV-1/4
      infected patients who completed a course of pegIFN/RBV were genotyped for both
      rs12979860 and ss469415590 markers. Logistic regression models including factors
      with univariate association with SVR and each genetic marker were elaborated. The
      area under the receiver operating-characteristic curve (AUROC) was calculated for
      each model and both were compared. RESULTS: Both markers were in LD (r2 = 0.82).
      For rs12979860, 66 (64.0%) CC versus 56 (33.1%) T allele carriers achieved SVR
      (Adjusted OR = 4.156, 95%CI = 2.388-7.232, p = 4.647*10-7). For ss469415590, 66
      (66.0%) TT/TT versus 56 (32.5%) -G allele carriers (Adjusted OR = 4.783, 95%CI =
      2.714-8.428, p = 6.153*10-8) achieved SVR. The AUROC of the model including
      rs12979860 was 0.742 (95%CI = 0.672-0.813) and of that based on ss469415590 was
      0.756 (95%CI = 0.687-0.826) (p = 0.780). CONCLUSIONS: The ss469415590 variant
      shows an equivalent performance to predict SVR to pegIFN/RBV than the rs2979860
      in Caucasian HCV-1/4-infected patients.

PMID- 24748395
TI  - Dihydroartemisinin-piperaquine vs. artemether-lumefantrine for first-line
      treatment of uncomplicated malaria in African children: a cost-effectiveness
      analysis.
AB  - BACKGROUND: Recent multi-centre trials showed that dihydroartemisinin-piperaquine
      (DP) was as efficacious and safe as artemether-lumefantrine (AL) for treatment of
      young children with uncomplicated P. falciparum malaria across diverse
      transmission settings in Africa. Longitudinal follow-up of patients in these
      trials supported previous findings that DP had a longer post-treatment
      prophylactic effect than AL, reducing the risk of reinfection and conferring
      additional health benefits to patients, particularly in areas with moderate to
      high malaria transmission. METHODS: We developed a Markov model to assess the
      cost-effectiveness of DP versus AL for first-line treatment of uncomplicated
      malaria in young children from the provider perspective, taking into
      consideration the post-treatment prophylactic effects of the drugs as reported by
      a recent multi-centre trial in Africa and using the maximum manufacturer drug
      prices for artemisinin-based combination therapies set by the Global Fund in
      2013. We estimated the price per course of treatment threshold above which DP
      would cease to be a cost-saving alternative to AL as a first-line antimalarial
      drug. RESULTS: First-line treatment with DP compared to AL averted 0.03 DALYs
      (95% CI: 0.006-0.07) and 0.001 deaths (95% CI: 0.00-0.002) and saved $0.96 (95%
      CI: 0.33-2.46) per child over one year. The results of the threshold analysis
      showed that DP remained cost-saving over AL for any DP cost below $1.23 per
      course of treatment. CONCLUSIONS: DP is superior to AL from both the clinical and
      economic perspectives for treatment of uncomplicated P. falciparum malaria in
      young children. A paediatric dispersible formulation of DP is under development
      and should facilitate a targeted deployment of this antimalarial drug. The use of
      DP as first-line antimalarial drug in paediatric malaria patients in moderate to
      high transmission areas of Africa merits serious consideration by health
      policymakers.

PMID- 24748396
TI  - Sericin accelerates the production of hyaluronan and decreases the incidence of
      polyspermy fertilization in bovine oocytes during in vitro maturation.
AB  - Fetal bovine serum (FBS) has been widely used as a supplement in the maturation
      medium of bovine oocytes in vitro. However, serum contains many undefined factors
      and is potentially infectious to humans and animals. As a serum replacement, we
      evaluated the feasibility of using the silk protein, sericin, derived from the
      cocoons of silkworm. To examine the rates of oocyte maturation and fertilization,
      cumulus-oocyte complexes were cultured in TCM-199 supplemented with 0.01%, 0.05%,
      0.1% or 0.15% sericin or 5% FBS. The sizes of the perivitelline space that might
      relate to polyspermy, the expressions of Has2 and CD44 mRNA, the amount of
      hyaluronan (hyaluronic acid: HA) contained in the oocytes and the rates of
      blastocyst formation following insemination were then compared between the
      oocytes cultured with 0.05% sericin and 5% FBS, because the polyspermy rates in
      oocytes cultured with 0.05% sericin were significantly lower than in those
      cultured with 5% FBS. After in vitro maturation (IVM), the mean size of the
      perivitelline space was significantly greater in oocytes cultured with sericin
      than in those cultured with FBS, although the rates of nuclear maturation,
      fertilization and blastocyst formation of oocytes under both IVM conditions were
      not significantly different. The expression of HAS2 and CD44 mRNA and the amount
      of HA in the denuded oocytes cultured with 0.05% sericin were significantly
      greater than in those cultured with FBS. These results indicate the feasibility
      of sericin as an alternative protein supplement for IVM in bovine oocytes. 

PMID- 24748397
TI  - Improvements of vaginal atrophy without systemic side effects after topical
      application of Pueraria mirifica, a phytoestrogen-rich herb, in postmenopausal
      cynomolgus macaques.
AB  - The estrogenic efficacy of topical vaginal application of Pueraria mirifica
      extract (PM) on the restoration of vaginal atrophy, and the presence of any
      systemic side effects, were investigated in postmenopausal cynomolgus macaques.
      Twelve postmenopausal cynomolgus macaques, with complete cessation of
      menstruation for at least 5 years before start of this experiment, were divided
      into three groups. They received a topical vaginal application daily of 0.1 or 1%
      (w/w) PM cream or a conjugated equine estrogen (CEE) cream (a mixture of estrone,
      equilin, 17beta-dihydroequilin, 17alpha-estradiol and 17alpha-dihydroequilin at
      0.625 mg total estrogen/g cream) for 28 days. Estrogenic efficacy was assessed
      weekly by vaginal cytology assay and vaginal pH measurement, whilst the plasma
      luteinizing hormone (LH) and sex skin coloration levels were determined at the
      end of each treatment period to evaluate the systemic side effects. PM
      significantly increased the proportion of superficial cells in a dose-dependent
      manner, with a similar efficacy between 1% (w/w) PM and CEE. Together with
      increased vaginal maturation, PM decreased the vaginal pH to acidic levels, as
      observed in the CEE group. PM induced no detected systemic side effects, whilst
      CEE decreased the plasma LH level and increased the reddish color of the sex skin
      during the posttreatment period. Topical vaginal treatment with PM stimulated the
      maturation of the vaginal epithelium without causing systemic side effects in
      postmenopausal monkeys. The implication is that PM could be a safer alternative
      to treat vaginal atrophy in postmenopausal women. 

PMID- 24748398
TI  - Transgenic pigs with pancreas-specific expression of green fluorescent protein.
AB  - The development and regeneration of the pancreas is of considerable interest
      because of the role of these processes in pancreatic diseases, such as diabetes.
      Here, we sought to develop a large animal model in which the pancreatic cell
      lineage could be tracked. The pancreatic and duodenal homeobox-1 (Pdx1) gene
      promoter was conjugated to Venus, a green fluorescent protein, and introduced
      into 370 in vitro-matured porcine oocytes by intracytoplasmic sperm injection
      mediated gene transfer. These oocytes were transferred into four recipient gilts,
      all of which became pregnant. Three gilts were sacrificed at 47-65 days of
      gestation, and the fourth was allowed to farrow. Seven of 16 fetuses obtained
      were transgenic (Tg) and exhibited pancreas-specific green fluorescence. The
      fourth recipient gilt produced a litter of six piglets, two of which were Tg. The
      founder Tg offspring matured normally and produced healthy first-generation (G1)
      progeny. A postweaning autopsy of four 27-day-old G1 Tg piglets confirmed the
      pancreas-specific Venus expression. Immunostaining of the pancreatic tissue
      indicated the transgene was expressed in beta-cells. Pancreatic islets from Tg
      pigs were transplanted under the renal capsules of NOD/SCID mice and expressed
      fluorescence up to one month after transplantation. Tg G1 pigs developed normally
      and had blood glucose levels within the normal range. Insulin levels before and
      after sexual maturity were within normal ranges, as were other blood biochemistry
      parameters, indicating that pancreatic function was normal. We conclude that Pdx1
      Venus Tg pigs represent a large animal model suitable for research on pancreatic
      development/regeneration and diabetes. 

PMID- 24748399
TI  - The effects of 2-chloroprocaine on coagulation and fibrinolysis in the
      parturient: an in vitro study.
AB  - PURPOSE: Amide local anesthetics are known to inhibit coagulation. 2
      chloroprocaine is the only ester agent used in obstetric anesthesia. It is used
      during obstetric emergencies, and also to supplement inadequate epidural block
      produced by amide local anesthetics. There is no study to date that has evaluated
      the effect of ester local anesthetics on blood coagulation and fibrinolysis in
      the parturient. METHODS: In this study, we obtained blood samples from healthy,
      term-parturients and mixed them with varying amounts of 2-chloroprocaine for
      final concentrations ranging from 0.26 to 7.8 mM. Thromboelastograph((r)) was
      used to study the coagulation profile of these samples. RESULTS: Chloroprocaine
      impaired coagulation in a dose dependent manner, with increased R and K, and
      decreased MA and alpha. The difference, when compared to saline controls, reached
      statistical significance at a dose of 7.8 mM. An additional significant finding
      was that 2-chloroprocaine also enhanced fibrinolysis. CONCLUSIONS: Amide local
      anesthetics are known to impair coagulation, but 2-chloroprocaine produced
      significant fibrinolysis in addition to decreasing coagulation. This is the first
      study to date to demonstrate fibrinolytic properties of an ester local
      anesthetic. Further study evaluations are required to determine the cause of the
      variation in fibrinolysis. There is also a need to address the mechanism of
      increased fibrinolysis observed with 2-chroloprocaine.

PMID- 24748400
TI  - Comparison of cognitive, ambulatory, and psychomotor recovery profiles after day
      care anesthesia with propofol and sevoflurane.
AB  - PURPOSE: We compared the recovery profile of propofol and sevoflurane when used
      for maintenance of anesthesia in elective day care operative procedures. METHODS:
      One hundred ASA physical status I and II patients, aged between 18 and 50 years,
      were randomly assigned to receive either propofol-nitrous oxide or sevoflurane
      nitrous oxide maintenance of anesthesia. Early and intermediate recovery in terms
      of cognitive and ambulatory functions was recorded. Psychomotor testing, in the
      form of Trieger dot test and digit symbol substitution test, were performed
      before surgery and in the post-anesthesia care unit at 15 min, 30 min, 1 h, 2 h,
      and 4 h following nitrous oxide switch-off to evaluate intermediate recovery.
      RESULTS: There were no significant differences in recovery of early cognitive
      functions between the two groups, except that patients in the sevoflurane group
      were more responsive at around 10 min following nitrous oxide switch-off and
      "recalled address" earlier than patients in the propofol group. There was no
      significant difference in between the two groups with regard to "home-readiness."
      CONCLUSIONS: Recovery from sevoflurane anesthesia, especially with regard to
      cognitive functions, may be slightly faster than from propofol, but the
      difference is not sufficiently significant to affect the time to "home-readiness"
      in patients undergoing day care surgery.

PMID- 24748401
TI  - Anesthesia for aortic reconstruction in a child with PHACE syndrome.
AB  - PHACE syndrome is a neurocutaneous syndrome characterized by the association of
      large cutaneous hemangiomas and the cardiac and cerebral vascular anomalies. We
      report a 6-year-old female with PHACE syndrome presented with left facial
      hemangiomas, cystic lesion in the cerebral posterior fossa, coarctation of the
      aorta, aplasia of the left vertebral artery and stenosis of the left internal
      carotid artery. Surgical repair of the aorta with left heart bypass under beating
      heart was scheduled. We monitored regional cerebral oxygen saturation (rSO2) with
      infrared spectroscopy in order to detect cerebral hypoperfusion. A decrease of
      rSO2 ipsilateral to the cerebrovascular anomalies occurred during anastomosis of
      the aorta, which was treated by reducing the flow rate of left heart bypass and
      by increasing the inhalational oxygen concentration. As children with PHACE
      syndrome are frequently accompanied with cerebrovascular anomalies and at a risk
      of cerebral hypoperfusion, prevention of cerebral hypoperfusion is crucially
      important during general anesthesia. 

PMID- 24748402
TI  - The mu opioid receptor activation does not affect ischemia-induced agonal
      currents in rat spinal ventral horn.
AB  - PURPOSE: Opioid-induced spastic paraplegia after transient spinal cord ischemia
      during aortic surgery has been reported. Opioids modulate neurotransmission
      through mu (MU) opioid receptors (MORs) in the spinal ventral horn. However,
      their effects during ischemic insult are not understood. METHODS: The effects of
      the selective MU agonist [D-Ala(2),-N-Me-Phe(4), Gly(5)-ol]enkephalin (DAMGO) on
      ischemia-induced agonal currents were examined in the spinal lamina IX neurons of
      neonatal rats by using the whole-cell patch-clamp technique. Ischemia was
      simulated in vitro by oxygen/glucose deprivation. RESULTS: DAMGO (1 MUM) produced
      outward currents in ~60% of spinal lamina IX neurons at a holding potential of 
      70 mV. Superfusion with ischemia-simulating medium elicited an agonal current.
      The latency was 457 +/- 18 s. Despite its neuromodulatory effects, DAMGO did not
      significantly change the latencies of the agonal currents with (440 +/- 23 s) or
      without (454 +/- 33 s) DAMGO-induced currents. CONCLUSION: Activation of MORs
      does not influence ongoing ischemia-induced neuronal death. Our findings indicate
      that MOR agonist administration should be suitable as an anesthetic during aortic
      surgery.

PMID- 24748403
TI  - Dynamics of optic canal and orbital cavity development revealed by microCT.
AB  - PURPOSE: Numerous studies have attempted to clarify the exact anatomy and
      variations of the optic canal with non-conclusive results due to its close
      proximity to many vulnerable structures. We sought to determine the dynamics of
      growth and development of these structures on fetal skulls, which will help us to
      better understand of gender and age-dependent variations, as well as fatal
      malformations. METHODS: Fifteen previously macerated fetal frontal and sphenoid
      bones were analyzed and the diameters of optic canal, and distance of orbit from
      frontomaxillary suture to frontozygomatic suture were measured using 3D
      reconstruction images obtained by micro-CT. RESULTS: Average diameter of the
      optic canal in 300 mm fetus was measured to be 1,546 +/- 36 um, in 400 mm fetus
      2,470 +/- 123 um and in 500 mm fetus 3,757 +/- 203 um. This trend indicates a
      linear enlargement of optic canal during the fetal period. During the same time
      period, diameter of the orbit enlarges from 12,319 +/- 559 um in 300 mm fetus to
      19,788 +/- 736 um in 500 mm fetus. Growth curve is significantly lower in
      comparison with the same curve in optic canal data. We also calculated the ratio
      of orbit diameter and optic canal diameter between those groups which decreased
      from a value of 7.9 +/- 0.4 for 300 mm fetus to 5.3 +/- 0.2 for 500 mm fetus.
      CONCLUSION: Dynamics of optic canal and orbital cavity development is different
      in early and late fetal period. Diameters of those structures are in better
      correlation with the fetal length.

PMID- 24748404
TI  - Protocols for staining of bile canalicular and sinusoidal networks of human,
      mouse and pig livers, three-dimensional reconstruction and quantification of
      tissue microarchitecture by image processing and analysis.
AB  - Histological alterations often constitute a fingerprint of toxicity and diseases.
      The extent to which these alterations are cause or consequence of compromised
      organ function, and the underlying mechanisms involved is a matter of intensive
      research. In particular, liver disease is often associated with altered tissue
      microarchitecture, which in turn may compromise perfusion and functionality.
      Research in this field requires the development and orchestration of new
      techniques into standardized processing pipelines that can be used to
      reproducibly quantify tissue architecture. Major bottlenecks include the lack of
      robust staining, and adequate reconstruction and quantification techniques. To
      bridge this gap, we established protocols employing specific antibody
      combinations for immunostaining, confocal imaging, three-dimensional
      reconstruction of approximately 100-MUm-thick tissue blocks and quantification of
      key architectural features. We describe a standard procedure termed 'liver
      architectural staining' for the simultaneous visualization of bile canaliculi,
      sinusoidal endothelial cells, glutamine synthetase (GS) for the identification of
      central veins, and DAPI as a nuclear marker. Additionally, we present a second
      standard procedure entitled 'S-phase staining', where S-phase-positive and S
      phase-negative nuclei (stained with BrdU and DAPI, respectively), sinusoidal
      endothelial cells and GS are stained. The techniques include three-dimensional
      reconstruction of the sinusoidal and bile canalicular networks from the same
      tissue block, and robust capture of position, size and shape of individual
      hepatocytes, as well as entire lobules from the same tissue specimen. In addition
      to the protocols, we have also established image analysis software that allows
      relational and hierarchical quantifications of different liver substructures
      (e.g. cells and vascular branches) and events (e.g. cell proliferation and
      death). Typical results acquired for routinely quantified parameters in adult
      mice (C57Bl6/N) include the hepatocyte volume (5,128.3 +/- 837.8 MUm(3)) and the
      fraction of the hepatocyte surface in contact with the neighbouring hepatocytes
      (67.4 +/- 6.7 %), sinusoids (22.1 +/- 4.8 %) and bile canaliculi (9.9 +/- 3.8 %).
      Parameters of the sinusoidal network that we also routinely quantify include the
      radius of the sinusoids (4.8 +/- 2.25 MUm), the branching angle (32.5 +/- 11.2
      degrees ), the length of intersection branches (23.93 +/- 5.9 MUm), the number of
      intersection nodes per mm(3) (120.3 * 103 +/- 42.1 * 10(3)), the average length
      of sinusoidal vessel per mm(3) (5.4 * 10(3) +/- 1.4 * 10(3)mm) and the percentage
      of vessel volume in relation to the whole liver volume (15.3 +/- 3.9) (mean +/-
      standard deviation). Moreover, the provided parameters of the bile canalicular
      network are: length of the first-order branches (7.5 +/- 0.6 MUm), length of the
      second-order branches (10.9 +/- 1.8 MUm), length of the dead-end branches (5.9 +/
      0.7 MUm), the number of intersection nodes per mm(3) (819.1 * 10(3) +/- 180.7 *
      10(3)), the number of dead-end branches per mm(3) (409.9 * 10(3) +/- 95.6 *
      10(3)), the length of the bile canalicular network per mm(3) (9.4 * 10(3) +/- 0.7
      * 10(3) mm) and the percentage of the bile canalicular volume with respect to the
      total liver volume (3.4 +/- 0.005). A particular strength of our technique is
      that quantitative parameters of hepatocytes and bile canalicular as well as
      sinusoidal networks can be extracted from the same tissue block. Reconstructions
      and quantifications performed as described in the current protocols can be used
      for quantitative mathematical modelling of the underlying mechanisms.
      Furthermore, protocols are presented for both human and pig livers. The technique
      is also applicable for both vibratome blocks and conventional paraffin slices. 

PMID- 24748405
TI  - Comparison of ARMS and direct sequencing for detection of EGFR mutation and
      prediction of EGFR-TKI efficacy between surgery and biopsy tumor tissues in NSCLC
      patients.
AB  - The relationship between epidermal growth factor receptor (EGFR) mutation status
      and EGFR-tyrosine kinase inhibitors (TKI) efficacy in non-small cell lung cancer
      (NSCLC) patients has been well established. However, there is no available
      standard to define the optimal testing method and specimen type required for the
      detection of EGFR mutations. In this study, we compare results of ADx
      amplification refractory mutation system (ARMS) and direct sequencing for the
      detection of EGFR mutation and prediction of EGFR-TKI efficacy for surgery and
      biopsy tumor tissues in 158 NSCLC patients. For 71 surgery samples, there were 13
      and 17 positive samples detected by direct sequencing and ARMS, respectively. For
      87 biopsy samples, direct sequencing and ADx-ARMS found 15 and 32 positive
      samples, respectively. For surgery samples, sensitivity of direct sequencing and
      ARMS was 72.2% (13/18) and 94.4% (17/18), respectively. For the biopsy samples,
      sensitivity of direct sequencing and ARMS was 44.1% (15/34) and 94.1% (32/34),
      respectively. For the biopsy and surgery samples, the ORRs for EGFR positive and
      negative patients detected by direct sequencing were 46.1 versus 16.7 and 66.7
      versus 1.1%, respectively. For ADx-ARMS, the ORR for EGFR positive patients was
      significantly higher than for negative patients (55.6 vs. 5.6%). The median
      progression-free survival time of patients with EGFR wild type detected by direct
      sequencing (4.2 months) was significantly longer than that of patients with wild
      type detected by ARMS (1.7 months). ARMS has a higher sensitivity and specificity
      than direct sequencing for EGFR detection of mutation in both surgical and biopsy
      samples, and the results from ARMS are more consistent with the efficacy of EGFR
      TKIs treatment.

PMID- 24748406
TI  - Vasohibin-1 expression detected by immunohistochemistry correlates with prognosis
      in non-small cell lung cancer.
AB  - Vasohibin-1 (VASH1) is a newly discovered angiogenesis inhibitor that is
      specifically expressed in human vascular endothelial cells in response to
      vascular endothelial growth factor and fibroblast growth factor-2. This study
      aimed to evaluate the expression of VASH1 in non-small cell lung cancer (NSCLC)
      and correlates its expression with the clinicopathological parameters and
      prognosis of the disease. Immunohistochemical analysis was used to determine the
      expression of VASH1 in NSCLC tissue and adjacent normal tissue from 84 patients.
      The relationship between VASH1 expression and clinicopathological indicators was
      examined with the chi-squared test. Moreover, the survival rate was calculated
      with the Kaplan-Meier survivor curve. Finally, the correlation between the
      indicators and patient survival was estimated with Cox analysis. VASH1 was high
      expressed in 63.1% of NSCLC tissues versus 21.4% of adjacent tissues (P < 0.01).
      High VASH1 expression in NSCLC tissue was correlated with clinicopathological
      features including lymph node status (P = 0.024) and TNM stage (P = 0.036). The
      Kaplan-Meier curve indicated that the patients with high VASH1 expression had
      significantly shorter survival than those with low VASH1 expression. In the
      multivariate Cox regression model, high VASH1 expression was identified as an
      independent prognostic factor for patients with NSCLC. High VASH1 expression is
      predictive of poor prognosis of NSCLC, implying that VASH1 may be a promising new
      target for targeted therapies for NSCLC.

PMID- 24748407
TI  - Periodontitis in cardiovascular disease patients with or without Marfan syndrome-
      a possible role of Prevotella intermedia.
AB  - BACKGROUND: Although periodontitis is a risk factor for cardiovascular disease
      (CVD), the influence of periodontitis on Marfan syndrome (MFS) with CVD is
      unclear. The aim of this study was to assess the relationship between periodontal
      bacterial burden and MSF with CVD. METHODS AND RESULTS: The subjects were
      patients with MFS with CVD (n = 47); age and gender matched non-MFS CVD patients
      (n = 48) were employed as controls. Full-mouth clinical measurements, including
      number of teeth, probing of pocket depth (PD), bleeding on probing (BOP) and
      community periodontal index (CPI) were recorded. We also evaluated the existence
      of three periodontal pathogens, Porphyromonas gingivalis, Aggregatibacter
      actinomycetemcomitans, and Prevotella intermedia using polymerase chain reaction
      assays. Serum antibody titers against the pathogens were also measured. We
      revealed that MFS with CVD patients had periodontitis more frequently than the
      age and gender matched non-MFS CVD control subjects. MFS with CVD patients had
      significantly severer periodontitis, fewer remaining teeth and deeper PD compared
      to the non-MFS CVD controls. Furthermore, the serum antibody titer level against
      Prevotella intermedia was significantly lower in MFS plus CVD patients compared
      to the non-MFS CVD patients. CONCLUSION: Periodontitis may influence the
      pathophysiology of cardiovascular complications in MFS patients. A specific
      periodontal pathogen might be a crucial therapeutic target to prevent CVD
      development.

PMID- 24748408
TI  - Scintigraphic detection of dual ectopic thyroid tissue: experience of a Chinese
      tertiary hospital.
AB  - PURPOSE: To assess scintigraphic pattern, clinical indication and relevance of
      dual ectopic thyroid tissue (ETT). Literature is reviewed for such cases.
      METHODS: In this 5-year retrospective study, we reviewed all thyroid
      scintigraphies in our data base. Patients diagnosed with suspected ETT were
      identified. Literature is reviewed. Statistics were done by one-way analysis of
      variance and least significant difference test. RESULTS: From 11905 thyroid
      scintigraphies during the 5-year period, we retrieved 121 patients eligible for
      analysis. The top two indications were assessing a palpable front neck mass to
      determine whether it was an ETT, and primary hypothyroidism. Patients were
      divided into 3 groups. Group 1 with single ETT (83 cases); group 2 with dual ETT
      (6 cases) and group 3 with athyroid (32 cases). Age and thyroid hormones were
      highest in group 2, and lowest in group 3. Thyrotropin was highest in group 3,
      and lowest in group 2. Thyroxine was given to hypothyroid patients, while no
      surgery was performed. There were 42 published cases with dual ETT, most of whom
      were under 30 years old. 38.10% of them were euthyroid, 33.33% hypothyroid, and
      21.43% subclinical hypothyroid. Most frequent ectopic positions included lingual
      (33.73%), sublingual (27.71%) and subhyoid (22.89%). CONCLUSIONS: In our cohort,
      incidence of dual ETT was 0.05% if the denominator was total number of thyroid
      scintigraphies. The incidence was 4.96% if the denominator was the number of
      patients with suspected ETT. Important clinical indication is a front neck
      palpable mass suggestive of an ETT. Important clinical relevance of recognizing
      the dual ETT pattern is to avoid inappropriate surgery. After reviewing all
      published cases, we find dual ETT is often seen in young patients. Most of such
      patients are euthyroid or mildly hypothyroid. Thyroid ectopia often resides in
      lingual, sublingual and subhyoid areas.

PMID- 24748409
TI  - Tolerance and safety of intravenous streptomycin therapy in patients with
      tuberculosis.

PMID- 24748410
TI  - Investigation of severe water problem in urban areas of a developing country: the
      case of Dhaka, Bangladesh.
AB  - The present study evaluated water supply geochemistry in Dhaka City, Bangladesh,
      to provide detailed trace level (subppb) water quality data that include major
      ions, low dissolved oxygen (DO) and toxic trace metals for sustainable
      development. Dhaka Groundwater, which almost uniformly meets the World Health
      Organization guideline, has become the preferred source. Due to groundwater
      depletion and an ever-increasing need to meet water demands by city residents,
      Dhaka water supply and sewerage authority has initiated the treatment of river
      water, despite the fact that very little is known about the geochemical
      structure, and trace metal content in the Dhaka water supply. Major ion
      composition of water samples was determined, and the results used to generate
      Stiff diagrams. The diagrams served to visually compare water from different
      sources based on units of mass/volume. Hydrochemical facies analysis showed
      supply ground and surface waters are comprised predominately of Ca-Na-Mg-HCO3 and
      Ca-Na-Mg-HCO3-Cl types. Spatial distribution of ions, and Na/Cl and Na/SiO2 molar
      ratio indicated that silicate weathering is the dominant geochemical process.
      Chemical data revealed that toxic Cr metal mobilization is associated with
      chemical hazards from the leather industry. The vulnerability of deep wells to
      contamination by As is governed by the geometry of induced groundwater flow paths
      and the geochemical conditions encountered between the shallow and deep regions
      of the aquifer. Quantifying total arsenic (As) and As from interlocking
      geochemical cycles (Fe, Mn) may assist in interpreting As dynamics in Dhaka well
      water. The surface source water was hypoxic to anoxic low DO associated with very
      high concentrations of biological oxygen demands, and electrical conductivity
      compared to industrial and non-industrial urban processes and standard activity
      guidelines. The results of this study should be applied to future research
      focused on the potential to improve water quality in urban and surrounding areas.

PMID- 24748411
TI  - Physiologically realistic and validated mathematical liver model reveals
      [corrected] hepatobiliary transfer rates for Gd-EOB-DTPA using human DCE-MRI
      data.
AB  - OBJECTIVES: Diffuse liver disease (DLD), such as non-alcoholic fatty liver
      disease (NASH) and cirrhosis, is a rapidly growing problem throughout the
      Westernized world. Magnetic resonance imaging (MRI), based on uptake of the
      hepatocyte-specific contrast agent (CA) Gd-EOB-DTPA, is a promising non-invasive
      approach for diagnosing DLD. However, to fully utilize the potential of such
      dynamic measurements for clinical or research purposes, more advanced methods for
      data analysis are required. METHODS: A mathematical model that can be used for
      such data-analysis was developed. Data was obtained from healthy human subjects
      using a clinical protocol with high spatial resolution. The model is based on
      ordinary differential equations and goes beyond local diffusion modeling, taking
      into account the complete system accessible to the CA. RESULTS: The presented
      model can describe the data accurately, which was confirmed using chi-square
      statistics. Furthermore, the model is minimal and identifiable, meaning that all
      parameters were determined with small degree of uncertainty. The model was also
      validated using independent data. CONCLUSIONS: We have developed a novel approach
      for determining previously undescribed physiological hepatic parameters in
      humans, associated with CA transport across the liver. The method has a potential
      for assessing regional liver function in clinical examinations of patients that
      are suffering of DLD and compromised hepatic function.

PMID- 24748412
TI  - Comparison of drug-induced sleep endoscopy and upper airway computed tomography
      in obstructive sleep apnea patients.
AB  - The purpose of the present study was to evaluate the associations between the
      findings of drug-induced sleep endoscopy (DISE) and upper airway computed
      tomography (UACT) in obstructive sleep apnea (OSA) patients. This study was a non
      randomized, prospective, clinical trial. We used DISE to identify the obstruction
      pattern according to VOTE classification. All 62 study subjects (all men) showed
      velum-related obstruction; 47 (75.8%) had lateral oropharyngeal obstruction, 45
      (72.6%) had tongue-base-related obstruction, and 6 (9.7%) had epiglottal
      obstruction. The following UACT measurements significantly differed between
      subjects with and without lateral oropharyngeal obstruction (P < 0.05): airway
      length, laryngopharynx length, mandibular plane to hyoid distance, minimum
      lateral dimension of the retroglossal airway, retropalatal
      anteroposterior/lateral dimension, and retroglossal anteroposterior/lateral
      dimension. None of the UACT measurements significantly differed between subjects
      with and without tongue-base-related or epiglottal obstruction. These results
      indicate that in OSA patients, obstruction related to the lateral oropharyngeal
      walls can be identified using these UACT measurements. Thus, UACT, which is
      performed during wakefulness, can partially replace DISE, which is both time
      consuming and costly.

PMID- 24748413
TI  - Instability and instrumentation failures after a PSO: a finite element analysis.
AB  - STUDY DESIGN: Finite element analysis. BACKGROUND DATA: Pedicle subtraction
      osteotomy (PSO) is associated with a high rate of mechanical complications and
      implant failures. The biomechanical reasons for these failures are unclear.
      OBJECTIVES: Using finite element analysis (FEA): to analyze the biomechanical
      instability after a PSO, to compare the effect of constructs with different rod
      contours and analyze the mechanical forces acting on these constructs to explain
      the mechanisms of failure. METHODS: A 3D validated FE model of the spine from L1
      to the sacrum was used. The model was modified to simulate a PSO of L4 in
      different situations: healthy, high dehydrated and completely degenerated discs.
      Loads were applied and range of motion (ROM) was measured. Pedicle screw
      constructs from L2 to S1 with different rod contours were added to the most
      instable scenario. Bending, torsion, shear moments and stress were measured.
      RESULTS: PSO alone had a moderate impact on the ROM of basic movements (flexion,
      extension and lateral bending). Secondary motion (torsion) in lateral bending
      increased 200 %. Greatest increase in ROM was observed with the PSO and
      degenerated discs. Secondary motion (torsion) in lateral bending increased +625
      %. The instability after a PSO is rotational. Mean reduction of ROM was 95 % for
      all constructs tested. Rod contour affected the location of bending moments and
      stress. Sharp angle bend showed maximum bending moments (2,208 Nmm) and stress at
      the PSO level. Smooth contour of the rod showed maximum bending moments (1,940
      Nmm) and stress at the sacral connection. Anterior support below the PSO reduced
      bending moments along the rod (-26 %). CONCLUSION: The instability observed after
      a PSO is mainly rotational and increases with disc degeneration. Shape of rod
      contour affects the location of maximum stress in the constructs. These findings
      may explain different instrumentation failures.

PMID- 24748414
TI  - Overexpression of horsegram (Macrotyloma uniflorum Lam.Verdc.) NAC
      transcriptional factor (MuNAC4) in groundnut confers enhanced drought tolerance.
AB  - The NAC family being the largest plant-specific transcription factors functions
      in diverse and vital physiological processes during development. NAC proteins are
      known to be crucial in imparting tolerance to plants against abiotic stresses,
      such as drought and salinity, but the functions of most of them are still
      elusive. In this study, we report for the first time expression of the MuNAC4, a
      member of NAC transcription factor from horsegram (Macrotyloma uniflorum)
      conferring drought tolerance. The groundnut (Arachis hypogaea) transgenics were
      generated using recombinant MuNAC4 binary vector transformation approach.
      Molecular analysis of these transgenic lines confirmed the stable gene
      integration and expression of the MuNAC4 gene. Twelve lines of T5 generation
      exhibited significantly enhanced tolerance to drought stress with proliferated
      lateral root growth as compared to wild types. Transgenics exposed to long-term
      desiccation stress assays showed increased lateral roots and greenish growth. The
      physiological parameters analysis also suggests that overexpression of MuNAC4
      plays a significant role in improving the water stress tolerance of transgenic
      groundnut, reducing the damage to membrane structures and enhancing osmotic
      adjustment and antioxidative enzyme regulation under stress. This study validates
      MuNAC4 as an important candidate gene for future phytoengineering approaches for
      drought tolerance in crop plants. 

PMID- 24748417
TI  - Addition of aprepitant improves protection against cisplatin-induced emesis when
      a conventional anti-emetic regimen fails.
AB  - OBJECTIVE: We investigated whether aprepitant, a neurokinin-1 antagonist, could
      decrease chemotherapy-induced nausea and vomiting (CINV) following cisplatin,
      when a conventional anti-emetic regimen had failed. METHODS: This was a
      prospective study (April 2011-April 2012) of patients with lung cancer, treated
      with cisplatin at the Beijing Cancer Hospital, and initially receiving
      granisetron, dexamethasone, and metoclopramide as anti-emetics. If patients
      experienced vomiting of grade >=2 and required rescue anti-emetic medications
      during the first cycle, oral aprepitant was added in subsequent cycles (day 1:
      125 mg; days 2-3: 80 mg once daily). Acute (day 1) and delayed (days 2-5) nausea
      and vomiting, use of rescue medications, and occurrence of adverse reactions were
      monitored after the start of chemotherapy. RESULTS: Twenty-five of 132 patients
      (18.9 %) were administered aprepitant for secondary prophylaxis against emesis
      during the second cycle of chemotherapy. The incidences of acute and delayed
      nausea were 52 and 100 % in the first cycle, but 8 and 72 % in the second cycle.
      The incidences of acute and delayed vomiting were 20 and 100 % in the first
      cycle, but 0 and 36 % in the second cycle. No patients required rescue
      medications or intravenous rehydration during the second cycle. Aprepitant was
      not associated with additional adverse events. CONCLUSIONS: In patients with lung
      cancer receiving cisplatin-based chemotherapy, the addition of aprepitant to a 5
      HT3 antagonist, dexamethasone, and metoclopramide improves protection against
      CINV when the conventional anti-emetic regimen fails.

PMID- 24748418
TI  - A phase II trial of Xeloda and oxaliplatin (XELOX) neo-adjuvant chemotherapy
      followed by surgery for advanced gastric cancer patients with para-aortic lymph
      node metastasis.
AB  - PURPOSE: Gastric cancer with para-aortic lymph node (PAN) involvement is regarded
      as advanced disease, and only chemotherapy is recommended from the guidelines. In
      unresectable cases, neoadjuvant chemotherapy could prolong survival if conversion
      to resectability could be achieved. METHODS: The study was a single-arm phase II
      trial. Patients who were diagnosed with gastric cancer and PAN involvement
      (Stations No. 16a2/16b1) were treated with capecitabine and oxaliplatin
      combination chemotherapy every 3 weeks for a maximum of six cycles. After every
      two cycles, abdominal computed tomographic scans were repeated to evaluate the
      response, and surgery was performed at the physician(')s discretion in patients
      with sufficient tumor response, followed by chemotherapy with the same regimen to
      complete a total of six cycles. The primary end point was the response rate of
      the preoperative chemotherapy. The secondary end points were R0 resection rate,
      progression-free survival (PFS), overall survival (OS), and adverse events.
      RESULTS: A total of 48 patients were enrolled. The response rate of the first
      line chemotherapy was 49.0 %, and the clinical benefit response was 85.1 %. After
      a median of four cycles of chemotherapy, 28 patients received surgery (58.3 %).
      The median PFS and OS of all patients were 10.0 and 29.8 months, respectively.
      Patients in the surgery group had much longer PFS (18.1 vs. 5.6 mo, P = 0.001)
      and OS (not reached vs. 12.5 mo, P = 0.016) compared with those in the non
      surgery group. CONCLUSIONS: For gastric cancer patients with PAN involvement,
      neoadjuvant chemotherapy with XELOX demonstrated a good response rate, and a
      sufficient R0 resection rate, with acceptable toxicities. Further study is needed
      to confirm the effectiveness of this regimen.

PMID- 24748419
TI  - Ultrasound, CT and FDG PET-CT of a duodenal granuloma in a dog.
AB  - A 12-year-old spayed female Yorkshire Terrier with intermittent vomiting was
      diagnosed with regional granulomatous enteritis through histopathological
      examination. On ultrasonography and computed tomography, a focal thickened
      duodenal wall showed a mass-like appearance with indistinct wall layers. Marked
      uptake of (18)F-fluorodeoxyglucose was observed from the mass on positron
      emission tomography-computed tomography. Regional granulomatous enteritis is a
      rare form of inflammatory bowel disease and may have imaging features similar to
      intestinal tumors. This is the first study describing the diagnostic imaging
      features of ultrasonography, computed tomography and positron emission tomography
      computed tomography for regional granulomatous enteritis in a dog. 

PMID- 24748420
TI  - Identification of matrix metalloproteinase-2 and -9 activities within intestinal
      mucosa of clinically healthy beagle dogs.
AB  - Matrix metalloproteinases (MMPs) 2 and 9 are zinc-dependent endopeptidases that
      contribute to the control of breakdown and reconstitution of extracellular matrix
      under both normal and pathological conditions. The main objective of this study
      was to identify the presence of MMP-2 and -9 in the mucosa of the small and large
      intestines of clinically healthy beagle dogs using gelatin zymography technique.
      Intestinal mucosa samples from four different parts of the intestine (duodenum,
      jejunum, ileum and colon) were taken from 12 healthy laboratory beagle dogs and
      examined histologically. Based on WSAVA histology standards, recorded findings of
      all samples were considered insignificant. Pro-MMP-2 and -9 activities were found
      in 17/48 (35%) and 25/48 (52%) of the samples, respectively. Among four different
      parts of the intestine of 12 dogs, the ileum had the highest positivity rates of
      7/12 (58.3%) and 8/12 (66.7%) for pro-MMP-2 and -9 activities, respectively.
      However, statistical analysis showed no significant difference of pro-MMP-2 and 
      9 activities between the separate parts of the intestine (P>0.05). None of the
      intestinal samples showed gelatinolytic activity corresponding to the control
      bands of active MMP-2 and MMP-9. This study showed that pro-MMP-2 and -9 could be
      detected in the intestinal mucosa of healthy dogs using zymography, which seems
      to be a useful tool to evaluate the role of MMP-2 and -9 in the pathogenesis of
      canine chronic enteropathies, including inflammatory bowel diseases. 

PMID- 24748421
TI  - Is regenerative medicine a new hope for kidney replacement?
AB  - The availability of kidney and other organs from matching donors is not enough
      for many patients on demand for organ transplant. Unfortunately, this situation
      is not better despite the many of new interesting projects of promoting family,
      cross or domino transplants. These inexorable global statistics forced medical
      researchers to find a new potential therapeutic option that would guarantee
      safety and efficacy for the treatment of ESRD comparable to kidney
      transplantation. The aim of our review is to summarize the scientific literature
      that relating to the modern as well as innovative experimental methods and
      possibilities of kidney regeneration and, in addition, to find whether the
      regenerative medicine field will be a new hope for curing the patient with renal
      disease complications. The most important achievements in the field of
      regenerative medicine of kidney, which were mentioned and described here, are
      currently cumulated in 4 areas of interest: stem cell-based therapies, neo
      kidneys with specially designed scaffolds or cell-seeded matrices, bioartificial
      kidneys and innovative nanotechnologically bioengineered solutions. Nowadays, we
      can add some remarks that the regenerative medicine is still insufficient to
      completely replace current therapy methods used in patients with chronic kidney
      disease especially with the end-stage renal disease where in many cases kidney
      transplantation is the only one chance. But we think that development of
      regenerative medicine especially in the last 20 years brings us more and more
      closer to solve many of today's problems at the frontier of nephrology and
      transplantology. 

PMID- 24748422
TI  - Change in physiological signals during mindfulness meditation.
AB  - Mindfulness meditation (MM) is an inward mental practice, in which a resting but
      alert state of mind is maintained. MM intervention was performed for a population
      of older people with high stress levels. This study assessed signal processing
      methodologies of electroencephalographic (EEG) and respiration signals during
      meditation and control condition to aid in quantification of the meditative
      state. EEG and respiration data were collected and analyzed on 34 novice
      meditators after a 6-week meditation intervention. Collected data were analyzed
      with spectral analysis and support vector machine classification to evaluate an
      objective marker for meditation. We observed meditation and control condition
      differences in the alpha, beta and theta frequency bands. Furthermore, we
      established a classifier using EEG and respiration signals with a higher accuracy
      at discriminating between meditation and control conditions than one using the
      EEG signal only. EEG and respiration based classifier is a viable objective
      marker for meditation ability. Future studies should quantify different levels of
      meditation depth and meditation experience using this classifier. Development of
      an objective physiological meditation marker will allow the mind-body medicine
      field to advance by strengthening rigor of methods.

PMID- 24748424
TI  - Leukemia and brain tumors among children after radiation exposure from CT scans:
      design and methodological opportunities of the Dutch Pediatric CT Study.
AB  - Computed tomography (CT) scans are indispensable in modern medicine; however, the
      spectacular rise in global use coupled with relatively high doses of ionizing
      radiation per examination have raised radiation protection concerns. Children are
      of particular concern because they are more sensitive to radiation-induced cancer
      compared with adults and have a long lifespan to express harmful effects which
      may offset clinical benefits of performing a scan. This paper describes the
      design and methodology of a nationwide study, the Dutch Pediatric CT Study,
      regarding risk of leukemia and brain tumors in children after radiation exposure
      from CT scans. It is a retrospective record-linkage cohort study with an expected
      number of 100,000 children who received at least one electronically archived CT
      scan covering the calendar period since the introduction of digital archiving
      until 2012. Information on all archived CT scans of these children will be
      obtained, including date of examination, scanned body part and radiologist's
      report, as well as the machine settings required for organ dose estimation. We
      will obtain cancer incidence by record linkage with external databases. In this
      article, we describe several approaches to the collection of data on archived CT
      scans, the estimation of radiation doses and the assessment of confounding. The
      proposed approaches provide useful strategies for data collection and confounder
      assessment for general retrospective record-linkage studies, particular those
      using hospital databases on radiological procedures for the assessment of
      exposure to ionizing or non-ionizing radiation.

PMID- 24748425
TI  - The increased risk of venous thromboembolism by advancing age cannot be
      attributed to the higher incidence of cancer in the elderly: the Tromso study.
AB  - Whether the high incidence of venous thromboembolism (VTE) in the elderly can be
      attributed to cancer is not well studied. We assessed the impact of cancer on
      risk of VTE in young, middle-aged and elderly. 26,094 subjects without a history
      of cancer or VTE were recruited from the Tromso study. Incident cancer (n =
      2,290) and VTE (n = 531) were recorded from baseline (1994-1995) through December
      31st, 2009. Cox regression with cancer as time-varying exposure was used to
      calculate hazard ratios with 95 % confidence intervals (CI). Overt cancer was
      associated with a fivefold (95 %CI 4.3, 6.7) increased risk of VTE, with an age
      dependent gradient from 26-fold (95 %CI 12.1, 56.5) increased in the young,
      ninefold (95 % CI 6.6, 12.7) increased in the middle-aged, and threefold (95 % CI
      2.5, 4.5) increased risk in the elderly. The population attributable risks were
      14, 27 and 18 %, respectively. CONCLUSION: The relative risk of VTE by cancer
      were higher in young compared to elderly subjects, but the proportion of VTEs in
      the population due to cancer did not differ much across age groups. Our findings
      indicate that the increased risk of VTE by advancing age cannot be attributed to
      higher incidence of cancer in the elderly.

PMID- 24748426
TI  - The transcription factor CHOP, a central component of the transcriptional
      regulatory network induced upon CCl4 intoxication in mouse liver, is not a
      critical mediator of hepatotoxicity.
AB  - Since xenobiotics enter the organism via the liver, hepatocytes must cope with
      numerous perturbations, including modifications of proteins leading to
      endoplasmic reticulum stress (ER-stress). This triggers a signaling pathway
      termed unfolded protein response (UPR) that aims to restore homeostasis or to
      eliminate disturbed hepatocytes by apoptosis. In the present study, we used the
      well-established CCl4 hepatotoxicity model in mice to address the questions
      whether CCl4 induces ER-stress and, if so, whether the well-known ER-stress
      effector CHOP is responsible for CCl4-induced apoptosis. For this purpose, we
      treated mice with a high dose of CCl4 injected i.p. and followed gene expression
      profile over time using Affymetrix gene array analysis. This time resolved gene
      expression analysis allowed the identification of gene clusters with
      overrepresented binding sites for the three most important ER-stress induced
      transcription factors, CHOP, XBP1 and ATF4. Such result was confirmed by the
      demonstration of CCl4-induced XBP1 splicing, upregulation of CHOP at mRNA and
      protein levels, and translocation of CHOP to the nucleus. Two observations
      indicated that CHOP may be responsible for CCl4-induced cell death: (1) Nuclear
      translocation of CHOP was exclusively observed in the pericentral fraction of
      hepatocytes that deteriorate in response to CCl4 and (2) CHOP-regulated genes
      with previously reported pro-apoptotic function such as GADD34, TRB3 and ERO1L
      were induced in the pericentral zone as well. Therefore, we compared CCl4 induced
      hepatotoxicity in CHOP knockout versus wild-type mice. Surprisingly, genetic
      depletion of CHOP did not afford protection against CCl4-induced damage as
      evidenced by serum GOT and GPT as well as quantification of dead tissue areas.
      The negative result was obtained at several time points (8, 24 and 72 h) and
      different CCl4 doses (1.6 and 0.132 g/kg). Overall, our results demonstrate that
      all branches of the UPR are activated in mouse liver upon CCl4 treatment.
      However, CHOP does not play a critical role in CCl4-induced cell death and cannot
      be considered as a biomarker strictly linked to hepatotoxicity. The role of
      alternative UPR effectors such as XBP1 remains to be investigated.

PMID- 24748427
TI  - Adherence to renal function monitoring guidelines in patients starting
      antihypertensive therapy with diuretics and RAAS inhibitors: a retrospective
      cohort study.
AB  - BACKGROUND: Acute kidney injury (AKI) might complicate antihypertensive therapy.
      In The Netherlands, general practitioner clinical practice guidelines provide
      clear recommendations on monitoring of renal function to minimize this risk. Our
      objective was to investigate how day-to-day clinical practice corresponds to the
      guidelines. METHODS: We conducted a retrospective cohort study in a dynamic
      population, using data on >9,000 adults that was retrieved from the Integrated
      Primary Care Information database. We investigated whether serum creatinine (SCR)
      was measured within 30 and 365 days after the start of (combined) use of a
      diuretic, an angiotensin-converting enzyme inhibitor, and/or angiotensin receptor
      blocker. We also investigated the association between calendar year, sex, type of
      therapy, risk factors for AKI and practice and SCR measurement. RESULTS: Of 6,593
      subjects who met the study criteria for single drug therapy, SCR was measured in
      1,233 subjects within 30 days and in 3,896 subjects within 365 days. For combined
      drug therapy recipients (n = 2,497), these were 545 and 1,687, respectively.
      Associated cumulative probabilities were 19 % and 66 % with single drug therapy,
      and 22 % and 74 % with combined drug therapy. Significant differences were
      observed between practices. SCR measurement was associated with other
      characteristics, except for sex. Within 365 days, SCR increased >30 % of baseline
      in 103 subjects (1.6 %) after the start of single drug therapy, and in 85 (3.4 %)
      subjects who initiated combined drug therapy. In the majority (>70 %) of these
      subjects, this did not result in subsequent monitoring or adjustment of
      antihypertensive treatment. CONCLUSIONS: Results from this study suggest that, on
      average, renal function is not monitored as strictly as recommended by relevant
      clinical practice guidelines.

PMID- 24748428
TI  - Adverse drug reaction reporting by patients: an overview of fifty countries.
AB  - BACKGROUND: The modalities and contributions to drug safety of patient adverse
      drug reaction reporting systems in 50 countries have been reviewed and analysed.
      METHODS: The means made available by National Health Competent Authorities (NCAs)
      for patients to report drug side effects were compared through literature review
      and questionnaire. RESULTS: Among the 50 countries included in this study, we
      found that direct patient reporting systems exist in 44 countries and represent 9
      % of total reports, the rest coming from healthcare professionals. Australia was
      the first, in 1964, and the United States has the system in which patients are
      the most involved. A total of 27 countries have a patient-specific reporting
      form, and 31 countries provide a form to complete online. In order to help
      patients, four countries constrain the description of the reaction and 12
      constrain the choice of drug on the reporting form. Most of the surveyed
      countries request the patient's medical history (30 countries) and concomitant
      therapies (41 countries). The total number of fields per form ranges from 6 to
      59, with a mean of 36 items. CONCLUSIONS: Most of the surveyed countries have
      implemented a patient adverse drug reaction reporting system. From this study, it
      seems that an online reporting form increases the rate of reporting. Currently,
      many different forms exist worldwide; these should be harmonized by considering
      the strengths and weaknesses of all existing forms. But above all, to increase
      the number of reports, each country should promote NCA-initiated adverse drug
      reactions reporting systems.

PMID- 24748429
TI  - HMGB1 enhances embryonic neural stem cell proliferation by activating the MAPK
      signaling pathway.
AB  - Neural stem cells (NSCs) are involved in neural tube formation. As the high
      mobility group box 1 (HMGB1) protein is involved in neurulation and is present at
      elevated levels in neural tube defects (NTDs) induced by hyperthermia, we have
      now investigated the effects of HMGB1 on proliferation, differentiation, and MAPK
      signaling pathways of NSCs in vitro. We constructed a lentivirus vector with
      HMGB1 siRNA and used it to infect NSCs. Down-regulation of HMGB1 expression was
      confirmed. Proliferation of NSCs was determined by MTS and nestin/BrdU double
      labeling. Differentiation of NSCs was assessed using beta-tubulinIII and GFAP.
      Knockdown of HMGB1 significantly suppressed NSC proliferation but hardly affected
      differentiation, which was regulated by decreased expression of MAPK signaling
      pathways. Thus, HMGB1 has beneficial effects on neurulation and may serve as a
      new target for the prevention of NTDs. 

PMID- 24748430
TI  - Biodesulfurization of dibenzothiophene and gas oil using a bioreactor containing
      a catalytic bed with Rhodococcus rhodochrous immobilized on silica.
AB  - Biodesulfurization (BDS) in a bioreactor packed with a catalytic bed of silica
      containing immobilized Rhodococcus rhodochrous was studied. Various bed lengths
      and support particle sizes were evaluated for BDS of dibenzothiophene (DBT) and
      gas oil. The sulfur-containing substrates were introduced separately into the
      bioreactor at different feed flows. Higher removal of sulfur from DBT and gas oil
      was achieved with a long bed, lower substrate flow, and larger sizes of
      immobilization particles. The packed bed bioreactor containing metabolic active
      cells was recycled and maintained BDS activity. 

PMID- 24748431
TI  - Identification and expression of the elongator protein 2 (Ajelp2) gene, a novel
      regeneration-related gene from the sea cucumber Apostichopus japonicus.
AB  - Elongator proteins comprise six subunits (ELP1-ELP6) and form protein complexes.
      The elongator protein 2 gene (elp2) encodes a protein with a WD40 repeats domain
      that acts as a scaffold for complex assembly. It also plays an important role in
      growth and development. In this study, the full-length cDNA of elongator protein
      2 (Ajelp2) was cloned from the sea cucumber Apostichopus japonicus (A. japonicus)
      using rapid amplification of cDNA ends PCR techniques and comprised 3,058 bp,
      including a 54 bp 5' untranslated (UTR), a 526 bp 3' UTR and a 2,478 bp open
      reading frame encoding a polypeptide of 825 amino acids. The Ajelp2 sequence
      showed high homology to 12 other species. The molecular weight and isoelectric of
      point the presumptive protein were 91.6 kDa and 5.84, respectively. In situ
      hybridization indicated that the gene is expressed in the body wall, intestine,
      respiratory tree and longitudinal muscle. The expression level of Ajelp2
      increased in recovering of organs in sea cucumber and showed it's the highest
      expression level at the 15th day in the intestine and respiratory tree. Its
      expression then gradually decreased to normal levels. In the body wall, the
      expression level of Ajelp2 was up-regulated and then down-regulated. These
      results indicated that Ajelp2 is involved in protein regulation during the
      regeneration process in the sea cucumber A. japonicus.

PMID- 24748432
TI  - Interaction network analysis revealed biomarkers in myocardial infarction.
AB  - Myocardial infarction (MI) is a serious heart disease. The cardiac cells of
      patients with MI will die due to lack of blood for a long time. In this study, we
      aimed to find new targets for MI diagnosis and therapy. We downloaded GSE22229
      including 12 blood samples from healthy persons and GSE29111 from Gene Expression
      Omnibus including 36 blood samples from MI patients. Then we identified
      differentially expressed genes (DEGs) in patients with MI compared to normal
      controls with p value < 0.05 and |logFC| > 1. Furthermore, interaction network
      and sub-network of these of these DEGs were constructed by NetBox. Linker genes
      were screened in the Global Network database. The degree of linker genes were
      calculated by igraph package in R language. Gene ontology and kyoto encyclopedia
      of genes and genomes pathway analysis were performed for DEGs and network
      modules. A total of 246 DEGs were identified in MI, which were enriched in the
      immune response. In the interaction network, LCK, CD247, CD3D, FYN, HLA-DRA, IL2,
      CD8A CD3E, CD4, CD3G had high degree, among which CD3E, CD4, CD3G were DEGs while
      others were linker genes screened from Global Network database. Genes in the sub
      network were also enriched in the immune response pathway. The genes with high
      degree may be biomarkers for MI diagnosis and therapy.

PMID- 24748433
TI  - Overexpression of microRNA-25 by withaferin A induces cyclooxygenase-2 expression
      in rabbit articular chondrocytes.
AB  - Increasing evidence supports the role of microRNAs (miRNA) in the regulation of
      inflammation in various human disorders. Several recent studies have demonstrated
      that microRNA-25 (miR-25) has multiple functions, and it affects the expression
      of inflammatory mediators. Withaferin A (WFA), a natural compound derived from
      the medicinal plant Withania somnifera, has shown the potential to be an
      effective drug for arthritis treatment in several preclinical and clinical
      studies. We investigated the role of miR-25 in the WFA-mediated up-regulation of
      cyclooxygenase-2 (COX-2) expression in rabbit articular chondrocytes. WFA induced
      COX-2 expression in a dose-dependent manner as analyzed by western blot analysis
      and immunofluorescence staining in rabbit articular chondrocytes. WFA up
      regulated miR-25 expression as determined by real-time PCR. Overexpression of miR
      25 in the presence of WFA increased the expression of COX-2 compared to that
      observed with just WFA treatment alone, as indicated by western blot analysis and
      Real-time PCR. Moreover, silencing of miR-25 by anti-miR25 inhibited COX-2
      expression in a dose-dependent manner. Since miR-25 up-regulation by WFA
      treatment induced the expression of COX-2 in rabbit articular chondrocytes, these
      findings collectively suggest that miR-25 mediates the WFA-induced inflammatory
      responses in chondrocytes. 

PMID- 24748435
TI  - CC-chemokine ligand 2 facilitates conditioned place preference to methamphetamine
      through the activation of dopamine systems.
AB  - Methamphetamine addiction is characterized by drug craving caused by stimulation
      of the reward system. Because neuroinflammation underlies several neurological
      disorders, we investigated whether CC-chemokine ligand 2 (CCL2) participates in
      the methamphetamine dependence using mice. Upregulation of CCL2 but not CC
      chemokine receptor 2 (CCR2), a dominant receptor for CCL2, mRNA in both the
      prefrontal cortex (PFC) and nucleus accumbens (NAC) was observed after
      methamphetamine (3 mg/kg, s.c.) administration. Using immunohistochemistry, high
      CCL2 protein levels localized to neurons in the PFC and NAC. In the conditioned
      place preference (CPP) test, methamphetamine (0.3 - 3 mg/kg, s.c.) induced a CPP,
      reflecting psychic dependence on methamphetamine, in a dose-dependent manner. The
      CPP to methamphetamine was attenuated by RS504393 (1 mg/kg, s.c.), a CCR2
      antagonist. Moreover, methamphetamine increased phosphorylated tyrosine
      hydroxylase (pTH) levels in the ventral tegmental area (VTA). Increased levels of
      pTH in the VTA by methamphetamine was also suppressed by RS504393. Furthermore,
      intracerebroventricular injection of recombinant CCL2 increased pTH levels in the
      VTA. Taken together, we demonstrate that activation of dopamine neurons, which
      enhances reward-system activity, via the CCL2-CCR2 axis plays a crucial role in
      psychic dependence on methamphetamine. Novel treatments targeting this machinery
      may be effective for drug addiction.

PMID- 24748434
TI  - Modern perspectives on numerical modeling of cardiac pacemaker cell.
AB  - Cardiac pacemaking is a complex phenomenon that is still not completely
      understood. Together with experimental studies, numerical modeling has been
      traditionally used to acquire mechanistic insights in this research area. This
      review summarizes the present state of numerical modeling of the cardiac
      pacemaker, including approaches to resolve present paradoxes and controversies.
      Specifically we discuss the requirement for realistic modeling to consider
      symmetrical importance of both intracellular and cell membrane processes (within
      a recent "coupled-clock" theory). Promising future developments of the complex
      pacemaker system models include the introduction of local calcium control,
      mitochondria function, and biochemical regulation of protein phosphorylation and
      cAMP production. Modern numerical and theoretical methods such as multi-parameter
      sensitivity analyses within extended populations of models and bifurcation
      analyses are also important for the definition of the most realistic parameters
      that describe a robust, yet simultaneously flexible operation of the coupled
      clock pacemaker cell system. The systems approach to exploring cardiac pacemaker
      function will guide development of new therapies such as biological pacemakers
      for treating insufficient cardiac pacemaker function that becomes especially
      prevalent with advancing age. 

PMID- 24748436
TI  - Platelet and growth factor concentrations in activated platelet-rich plasma: a
      comparison of seven commercial separation systems.
AB  - Platelet-rich plasma (PRP) is blood plasma that has been enriched with platelets.
      It holds promise for clinical use in areas such as wound healing and regenerative
      medicine, including bone regeneration. This study characterized the composition
      of PRP produced by seven commercially available separation systems (JP200, GLO
      PRP, Magellan Autologous Platelet Separator System, KYOCERA Medical PRP Kit,
      SELPHYL, MyCells, and Dr. Shin's System THROMBO KIT) to evaluate the platelet,
      white blood cell, red blood cell, and growth factor concentrations, as well as
      platelet-derived growth factor-AB (PDGF-AB), transforming growth factor beta-1
      (TGF-beta1), and vascular endothelial growth factor (VEGF) concentrations. PRP
      prepared using the Magellan Autologous Platelet Separator System and the KYOCERA
      Medical PRP Kit contained the highest platelet concentrations. The mean PDGF-AB
      concentration of activated PRP was the highest from JP200, followed by the
      KYOCERA Medical PRP Kit, Magellan Autologous Platelet Separator System, MyCells,
      and GLO PRP. TGF-beta1 and VEGF concentrations varied greatly among individual
      samples, and there was almost no significant difference among the different
      systems, unlike for PDGF. The SELPHYL system produced PRP with low concentrations
      of both platelets and growth factors. Commercial PRP separation systems vary
      widely, and familiarity with their individual advantages is important to extend
      their clinical application to a wide variety of conditions. 

PMID- 24748437
TI  - Pontibacter humi sp. nov., isolated from mountain soil.
AB  - A Gram-negative, aerobic, non-motile, rod-shaped bacterial strain, designated as
      SWU8(T), was isolated from a mountain soil collected in Seoul Women's University
      campus at South Korea. Phylogenic analysis, using 16S rRNA gene sequence of the
      new isolate, showed that strain SWU8(T) belongs to the genus Pontibacter. The
      highest sequence similarities were 96.2 % with Pontibacter saemangeumensis
      GCM0142(T), 95.5 % with Pontibacter toksunensis ZLD-7(T), 95.3 % with Pontibacter
      roseus DSM 17521(T), and 95.1 % with Pontibacter odishensis JC130(T).
      Chemotaxonomic data showed that the most abundant fatty acids were summed feature
      4 (comprising iso-C(17:1) I/anteiso-C(17:1) B; 26.9 %), iso-C(15:0) (25.6 %), and
      iso-C(17:0) 3OH (10.6 %), and major polar lipid was phosphatidylethanolamine. The
      DNA G+C content of strain SWU8(T) was 48.5 mol%. Together, the phenotypic,
      phylogenetic, and chemotaxonomic data supported that strain SWU8(T) presents a
      novel species of the genus Pontibacter, for which the name Pontibacter humi sp.
      nov. is proposed. The type strain is SWU8(T) (=KEMC 9004-131(T) = JCM 19178(T)).

PMID- 24748438
TI  - Production and in vivo antioxidant activity of Zn, Ge, Se-enriched mycelia by
      Cordyceps sinensis SU-01.
AB  - Cordyceps sinensis, a traditionally edible and medicinal fungus in China, cannot
      be artificially solid-cultured. Zinc (Zn), germanium (Ge), and selenium (Se) are
      the essential trace elements for human body. In this work, C. sinensis SU-01 was
      cultivated in liquid medium simultaneously containing Zn, Ge, and Se. The
      bioactive ingredients and in vivo antioxidant activities of Zn, Ge, Se-enriched
      mycelia (ZGSM) of C. sinensis SU-01 were investigated. Under the determined
      conditions, the Zn, Ge, and Se contents of ZGSM were 2543.16 +/- 158.92, 1873.85
      +/- 81.82, and 1260.16 +/- 107.12 MUg/g, respectively. The optimal concentrations
      of Zn, Ge, and Se had a positive effect on biosynthesis of protein,
      polysaccharide, cordycepic acid, and amino acids. The activities of glutathione
      peroxidase (GSH-Px) and superoxide dismutase (SOD) of mice blood were 3.72 +/-
      0.15 and 28.74 +/- 2.53 % higher than that of control, respectively, and the
      content of malondialdehyde (MDA) was 41.01 +/- 3.66 % lower than that of control.

PMID- 24748439
TI  - Antibiotic resistance among cultured bacterial isolates from bioethanol
      fermentation facilities across the United States.
AB  - Bacterial contamination of fuel ethanol fermentations by lactic acid bacteria
      (LAB) can have crippling effects on bioethanol production. Producers have had
      success controlling bacterial growth through prophylactic addition of antibiotics
      to fermentors, yet concerns have arisen about antibiotic resistance among the
      LAB. Here, we report on mechanisms used by 32 LAB isolates from eight different
      US bioethanol facilities to persist under conditions of antibiotic stress.
      Minimum inhibitory concentration assays with penicillin, erythromycin, and
      virginiamycin revealed broad resistance to each of the antibiotics as well as
      high levels of resistance to individual antibiotics. Phenotypic assays revealed
      that antibiotic inactivation mechanisms contributed to the high levels of
      individual resistances among the isolates, especially to erythromycin and
      virginiamycin, yet none of the isolates appeared to use a beta-lactamase. Biofilm
      formation was noted among the majority of the isolates and may contribute to
      persistence under low levels of antibiotics. Nearly all of the isolates carried
      at least one canonical antibiotic resistance gene and many carried more than one.
      The erythromycin ribosomal methyltransferase (erm) gene class was found in 19 of
      32 isolates, yet a number of these isolates exhibit little to no resistance to
      erythromycin. The erm genes were present in 15 isolates that encoded more than
      one antibiotic resistance mechanism, suggestive of potential genetic linkages. 

PMID- 24748440
TI  - Spirosoma radiotolerans sp. nov., a gamma-radiation-resistant bacterium isolated
      from gamma ray-irradiated soil.
AB  - A Gram-negative, short-rod-shaped bacterial strain with gliding motility,
      designated as DG5A(T), was isolated from a rice field soil in South Korea.
      Phylogenic analysis using 16S rRNA gene sequence of the new isolate showed that
      strain DG5A(T) belong to the genus Spirosoma in the family Spirosomaceae, and the
      highest sequence similarities were 95.5 % with Spirosoma linguale DSM 74(T), 93.4
      % with Spirosoma rigui WPCB118(T), 92.8 % with Spirosoma luteum SPM-10(T), 92.7 %
      with Spirosoma spitsbergense SPM-9(T), and 91.9 % with Spirosoma panaciterrae
      Gsoil 1519(T). Strain DG5A(T) revealed resistance to gamma and UV radiation.
      Chemotaxonomic data showed that the most abundant fatty acids were summed feature
      C(16:1) omega7c/C(16:1) omega6c (36.90 %), C(16:1) omega5c (29.55 %), and iso
      C(15:0) (14.78 %), and the major polar lipid was phosphatidylethanolamine (PE).
      The DNA G+C content of strain DG5A(T) was 49.1 mol%. Together, the phenotypic,
      phylogenetic, and chemotaxonomic data supported that strain DG5A(T) presents a
      novel species of the genus Spirosoma, for which the name Spirosoma radiotolerans
      sp. nov., is proposed. The type strain is DG5A(T) (=KCTC 32455(T) = JCM19447(T)).

PMID- 24748441
TI  - The gut bacterial communities associated with lab-raised and field-collected ants
      of Camponotus fragilis (Formicidae: Formicinae).
AB  - Camponotus is the second largest ant genus and known to harbor the primary
      endosymbiotic bacteria of the genus Blochmannia. However, little is known about
      the effect of diet and environment changes on the gut bacterial communities of
      these ants. We investigated the intestinal bacterial communities in the lab
      raised and field-collected ants of Camponotus fragilis which is found in the
      southwestern United States and northern reaches of Mexico. We determined the
      difference of gut bacterial composition and distribution among the crop, midgut,
      and hindgut of the two types of colonies. Number of bacterial species varied with
      the methods of detection and the source of the ants. Lab-raised ants yielded 12
      and 11 species using classical microbial culture methods and small-subunit rRNA
      genes (16S rRNAs) polymerase chain reaction-restriction fragment-length
      polymorphism analysis, respectively. Field-collected ants yielded just 4 and 1-3
      species using the same methods. Most gut bacterial species from the lab-raised
      ants were unevenly distributed among the crop, midgut, and hindgut, and each
      section had its own dominant bacterial species. Acetobacter was the prominent
      bacteria group in crop, accounting for about 55 % of the crop clone library.
      Blochmannia was the dominant species in midgut, nearly reaching 90 % of the
      midgut clone library. Pseudomonas aeruginosa dominated the hindgut, accounting
      for over 98 % of the hindgut clone library. P. aeruginosa was the only species
      common to all three sections. A comparison between lab-raised and field-collected
      ants, and comparison with other species, shows that gut bacterial communities
      vary with local environment and diet. The bacterial species identified here were
      most likely commensals with little effect on their hosts or mild pathogens
      deleterious to colony health.

PMID- 24748442
TI  - Methodological reporting quality of randomized controlled trials in three spine
      journals from 2010 to 2012.
AB  - PURPOSE: To elucidate the methodological reporting quality of randomized
      controlled trials (RCTs) in three spine journals from 2010 to 2012. METHODS: In
      this study, we summarized the methodological report of RCTs in three major spine
      journals, including the Spine Journal, Spine and the European Spine Journal from
      2010 to 2012. The methodological reporting quality, including the allocation
      sequence generation, allocation concealment, blinding and sample size
      calculation, was revealed. Number of patients, funding source, type of
      intervention and country were also retrieved from each trial. The methodological
      reporting quality was descriptively reported. RESULTS: Ninety trials were
      involved and 57.8% (52/90) reported adequate allocation sequence generation,
      46.7% (42/90) reported adequate allocation concealment, 34.4% (31/90) reported
      adequate blinding and 37.8% (34/90) reported adequate sample size calculation.
      CONCLUSIONS: This study shows that the methodological reporting quality of RCTs
      in the spine field needs further improvement.

PMID- 24748443
TI  - Association between vitamin D status and COPD phenotypes.
AB  - BACKGROUND: It has been suggested that identifying phenotypes in chronic
      obstructive pulmonary disease (COPD) might improve treatment outcome and the
      accuracy of prediction of prognosis. In observational studies vitamin D
      deficiency has been associated with decreased pulmonary function, presence of
      emphysema and osteoporosis, upper respiratory tract infections, and systemic
      inflammation. This could indicate a relationship between vitamin D status and
      COPD phenotypes. The aim of this study was to assess the association between
      vitamin D levels and COPD phenotypes. In addition, seasonality of vitamin D
      levels was examined. METHODS: A total of 91 patients from a Danish subpopulation
      of the "Evaluation of COPD Longitudinally to Identify Predictive Surrogate End
      points" cohort took part in a biomarker substudy. Vitamin D concentration was
      measured from blood samples taken at two visits, approximately 6 months apart.
      The participants were 40-75-year-old patients with COPD and had a smoking history
      of >10 pack-years. RESULTS: Fifty-six patients had 25-hydroxyvitamin D measured
      from blood samples from both visits. In the final model of the multivariate
      analyses, the factors that were associated with vitamin D deficiency at the first
      visit were age (OR: 0.89, p = 0.02) and summer season (OR: 3.3, p = 0.03).
      Factors associated with vitamin D level also at the first visit were age (B: 0.9,
      p = 0.02) and 6 min walking distance (B: 0.05, p = 0.01). CONCLUSION: Vitamin D
      was not associated with COPD phenotypes and season did not seem to be a
      determinant of vitamin D levels in patients with moderate to severe COPD.

PMID- 24748444
TI  - Estimation of species extinction: what are the consequences when total species
      number is unknown?
AB  - The species-area relationship (SAR) is known to overestimate species extinction
      but the underlying mechanisms remain unclear to a great extent. Here, I show that
      when total species number in an area is unknown, the SAR model exaggerates the
      estimation of species extinction. It is proposed that to accurately estimate
      species extinction caused by habitat destruction, one of the principal
      prerequisites is to accurately total the species numbers presented in the whole
      study area. One can better evaluate and compare alternative theoretical SAR
      models on the accurate estimation of species loss only when the exact total
      species number for the whole area is clear. This presents an opportunity for
      ecologists to simulate more research on accurately estimating Whittaker's gamma
      diversity for the purpose of better predicting species loss. 

PMID- 24748445
TI  - Feasibility of hydrofluoric acid etched sand particles for enrichment and
      determination of polychlorinated biphenyls at trace levels in environmental water
      samples.
AB  - This study aims to investigate the feasibility of etched sand particles being
      used as solid-phase extraction adsorbents to enrich polychlorinated biphenyls
      (PCBs), which are typical persistent organic pollutants in the environment, at
      trace levels. Gas chromatography-tandem mass spectrometry was selected to detect
      the compounds. Etched sand particles exhibited excellent merits on the enrichment
      of PCBs. Related important factors affecting extraction efficiencies were
      investigated and optimized in detail. Under optimized conditions, low limits of
      detection (0.42 to 3.69 ng L(-1)), wide linear range (10 to 1,000 ng L(-1)), and
      high repeatability (1.9 to 8.2%) were achieved. The developed method was
      validated with several real water samples, and satisfactory results were
      obtained. All of these findings indicate that etched sand particles would be
      useful for the enrichment and determination of organic pollutants at trace levels
      in water samples.

PMID- 24748446
TI  - A biocatalytic cascade with several output signals--towards biosensors with
      different levels of confidence.
AB  - The biocatalytic cascade based on enzyme-catalyzed reactions activated by several
      biomolecular input signals and producing output signal after each reaction step
      was developed as an example of a logically reversible information processing
      system. The model system was designed to mimic the operation of concatenated AND
      logic gates with optically readable output signals generated at each step of the
      logic operation. Implications include concurrent bioanalyses and data
      interpretation for medical diagnostics. 

PMID- 24748447
TI  - Determination of bis-carboxyethyl germanium sesquioxide by gas chromatography
      with microwave-induced plasma-atomic emission detection after derivatization with
      alkyl chloroformates.
AB  - Organic germanium compounds, especially Ge-132, more corrctly denoted as bis-beta
      carboxyethyl germanium sesquioxide ([Ge(=O)CH2CH2CO2H]2O), are of continued
      interest as they are said to promote health and display anticancer activity.
      Although these beneficial effects have never been substantiated by comprehensive
      clinical studies, this drug can still be obtained through various sources and is
      usually marketed as a nutritional supplementation rather than an anticancer
      medication. As the quality standards under which this drug is produced are
      unknown, the need for an effective quality control of these products arises. To
      date, Ge-132 is considered generally as a safe compound for application in
      contrast to inorganic germanium which demonstrates severe renal toxicity. In this
      paper, a new approach to the determination of Ge-132, based on derivatization by
      ethyl chloroformate reagent (ECF), in the presence of ethanol and pyridine in the
      mixture, and subsequent analysis by gas chromatography coupled with microwave
      induced plasma-atomic emission detection (GC-MIP-AED), is reported. Reaction
      conditions of the derivatization procedure were optimized with particular respect
      to the reagent (ECF) and catalyst (pyridine) concentrations. The proposed method
      is capable of distinguishing Ge-132 from inorganic germanium. The derivatization
      procedure was also tested with the use of methyl chloroformate (MCF) as
      alternative reagent, providing interesting additional information about the
      nature of the final product and the proposed reaction scheme. Among the two types
      of chloroformates, i.e., MCF and ECF, the latter proved to be more suitable for
      the proposed method, providing a calibration curve of superior sensitivity and
      linearity compared with the one obtained with MCF. The method was applied
      successfully in three real samples, two food supplements, and one commercially
      available fertilizer. The analysis of the Ge-132 derivative showed good linearity
      in the concentration of 1-250 mg L(-1) (r (2) = 0.9986) and a satisfactory
      precision (RSD = 6.8%), which qualifies the proposed method for the speciation
      analysis of Ge in various matrices.

PMID- 24748449
TI  - Assessment of microbial communities associated with fermentative-methanogenic
      biodegradation of aromatic hydrocarbons in groundwater contaminated with a
      biodiesel blend (B20).
AB  - A controlled field experiment was conducted to assess the potential for
      fermentative-methanogenic biostimulation (by ammonium-acetate injection) to
      enhance biodegradation of benzene, toluene, ethylbenzene and xylenes (BTEX) as
      well as polycyclic aromatic hydrocarbons (PAHs) in groundwater contaminated with
      biodiesel B20 (20:80 v/v soybean biodiesel and diesel). Changes in microbial
      community structure were assessed by pyrosequencing 16S rRNA analyses. BTEX and
      PAH removal began 0.7 year following the release, concomitantly with the increase
      in the relative abundance of Desulfitobacterium and Geobacter spp. (from 5 to
      52.7 % and 15.8 to 37.3 % of total Bacteria 16S rRNA, respectively), which are
      known to anaerobically degrade hydrocarbons. The accumulation of anaerobic
      metabolites acetate and hydrogen that could hinder the thermodynamic feasibility
      of BTEX and PAH biotransformations under fermentative/methanogenic conditions was
      apparently alleviated by the growing predominance of Methanosarcina. This
      suggests the importance of microbial population shifts that enrich microorganisms
      capable of interacting syntrophically to enhance the feasibility of fermentative
      methanogenic bioremediation of biodiesel blend releases.

PMID- 24748448
TI  - Challenges in modelling the cost effectiveness of various interventions for
      cardiovascular disease.
AB  - OBJECTIVES: Decision analytic modelling is essential in performing cost
      effectiveness analyses (CEAs) of interventions in cardiovascular disease (CVD).
      However, modelling inherently poses challenges that need to be dealt with since
      models always represent a simplification of reality. The aim of this study was to
      identify and explore the challenges in modelling CVD interventions. METHODS: A
      document analysis was performed of 40 model-based CEAs of CVD interventions
      published in high-impact journals. We analysed the systematically selected papers
      to identify challenges per type of intervention (test, non-drug, drug, disease
      management programme, and public health intervention), and a questionnaire was
      sent to the corresponding authors to obtain a more thorough overview. Ideas for
      possible solutions for the challenges were based on the papers, responses,
      modelling guidelines, and other sources. RESULTS: The systematic literature
      search identified 1,720 potentially relevant articles. Forty authors were
      identified after screening the most recent 294 papers. Besides the challenge of
      lack of data, the challenges encountered in the review suggest that it was
      difficult to obtain a sufficiently valid and accurate cost-effectiveness
      estimate, mainly due to lack of data or extrapolating from intermediate outcomes.
      Despite the low response rate of the questionnaire, it confirmed our results.
      CONCLUSIONS: This combination of a review and a survey showed examples of CVD
      modelling challenges found in studies published in high-impact journals.
      Modelling guidelines do not provide sufficient guidance in resolving all
      challenges. Some of the reported challenges are specific to the type of
      intervention and disease, while some are independent of intervention and disease.

PMID- 24748451
TI  - Characterisation of nanomaterials in biological samples.

PMID- 24748452
TI  - Comprehensive identification of the binding sites of cisplatin in hen egg white
      lysozyme.
AB  - Platinum drugs have become one of the most important kinds of chemotherapy
      agents, and the interactions of these drugs with proteins play very important
      roles in their side effects and drug resistance. However, it is still a challenge
      to determine the binding sites of platinum drugs in proteins with multiple
      disulfide bonds and stable three-dimensional structures using mass spectrometry.
      Here, the interaction between cisplatin and hen egg white lysozyme (HEWL), a
      multi-disulfide-bond-containing protein with a stable three-dimensional
      structure, was investigated using Fourier transform ion cyclotron resonance mass
      spectrometry. Typical disulfide bond reduction with dithiothreitol/tris(2
      carboxyethyl)phosphine before trypsin digestion destroyed the binding of
      cisplatin to HEWL, and no platination sites were found. Efficient trypsin
      digestion methods for HEWL-cisplatin adducts were developed to avoid the loss of
      platinum binding to protein. At 55  degrees C, platinated HEWL was digested
      directly by trypsin in 6 h, and multiple platinated peptides were observed. In
      60% acetonitrile, the digestion time of platinated HEWL was shortened to 2 h, and
      most of the platinated peptides were observed. In addition, the reduction of the
      disulfide bonds of HEWL greatly accelerated the reaction between HEWL and
      cisplatin, and the potential binding sites of cisplatin in reduced HEWL could be
      easily recognized. On the basis of the above-mentioned methods, multiple binding
      sites of cisplatin in HEWL were first identified by mass spectrometry.

PMID- 24748453
TI  - Preparation of chlorocholine chloride/urea deep eutectic solvent-modified silica
      and an examination of the ion exchange properties of modified silica as a Lewis
      adduct.
AB  - Chlorocholine chloride/urea (ClChCl-urea), a deep eutectic solvent (DES), was
      applied successfully to the modification of silica. The resulting modified silica
      was characterized by Fourier transform infrared spectroscopy, Brunauer-Emmett
      Teller analysis, and elemental analysis. Based on the ClChCl-urea modification of
      silica, the ClChCl-urea-modified silica is a Lewis adduct with ion exchange
      properties, and ferulic acid was adsorbed on the ClChCl-urea-modified silica via
      an ion exchange process. The adsorbed percentage of ferulic acid increased with
      the increasing amount of modified silica, and a high adsorbed percentage of 89%
      could be obtained by the ion exchange process. The Freundlich isotherm used to
      describe the adsorption of ferulic acid on the modified silica by ion exchange
      showed a good correlation (R(2) = 0.93). Based on the characterization of the
      structure and the analysis of the ion exchange property of the ClChCl-urea
      modified silica, the modified silica as a potential medium can be applied in some
      analytical technologies such as solid phase extraction, chromatography, and so
      on.

PMID- 24748454
TI  - Invasive Geotrichum clavatum fungal infection in an acute myeloid leukaemia
      patient: a case report and review.
AB  - Invasive Geotrichum clavatum fungal infections are extremely rare and unusual,
      occurring nearly exclusively in patients experiencing prolonged neutropenia
      during the treatment for acute myeloid leukaemia. Several groups of cases of
      fatal G. clavatum infection were reported in France between 2011 and 2012, but
      the ecological niche has not yet been identified. We report a case of a 32-year
      old patient with acute myeloid leukaemia who developed G. clavatum sepsis with
      primary peritonitis, hepatic nodular lesions, and multivisceral failure during
      aplasia after induction followed by salvage chemotherapy. He was treated with
      voriconazole and is still alive 1 year after with controlled disease. We then
      discuss the epidemiological, clinical, and therapeutic features of these serious
      fungal infections compared to the published data. 

PMID- 24748455
TI  - A case of thyroid storm with a markedly elevated level of circulating soluble
      interleukin-2 receptor complicated by multiple organ failure and disseminated
      intravascular coagulation syndrome.
AB  - Thyroid storm (TS) is a life-threatening endocrine emergency. However, the
      pathogenesis of TS is poorly understood. A 40-year-old man was admitted to a
      nearby hospital with body weight loss and jaundice. Five days after a contrasted
      abdominal computerized tomography (CT) scan, he exhibited high fever and
      disturbance of consciousness. He was diagnosed with TS originating from untreated
      Graves' disease and was transferred to the intensive care unit (ICU) of our
      hospital. The patient exhibited impaired consciousness (E4V1M4 in Glasgow coma
      scale), high fever (39.3 degrees C), and atrial flutter with a pulse rate
      162/min, and was complicated by heart failure, acute hepatic failure, and
      disseminated intravascular coagulation syndrome (DIC). His circulating level of
      soluble interleukin-2 receptor (sIL-2R), a serum marker of an activated immune
      response, was highly elevated (7,416 U/mL, reference range: 135-483). Multiple
      organ failure (MOF) and DIC were successfully managed by multimodality treatments
      using inorganized iodide, glucocorticoids, anti-thyroid drugs, beta-blockers, and
      diuretics as well as an anticoagulant agent and the transfusion of platelet
      concentrate and fresh frozen plasma. sIL-2R levels gradually decreased during the
      initial treatment, but were still above the reference range even after
      thyroidectomy. Mild elevations in serum levels of sIL-2R have previously been
      correlated with thyroid hormone levels in non-storm Graves' disease. The present
      study demonstrated, for the first time, that circulating sIL-2R levels could be
      markedly elevated in TS. The marked increase in sIL-2R levels was speculated to
      represent an inappropriate generalized immune response that plays an unknown role
      in the pathogenesis of TS.

PMID- 24748456
TI  - A missense single-nucleotide polymorphism in the sialic acid acetylesterase
      (SIAE) gene is associated with anti-PIT-1 antibody syndrome.
AB  - A novel clinical entity related to autoimmune polygladular syndrome (APS) termed
      "anti-PIT-1 antibody syndrome" is characterized by a presence of circulating
      autoantibody against the pituitary-specific transcriptional factor-1 (PIT-1) with
      acquired specific defect in GH, PRL, and TSH. Although autoimmunity to PIT-1 has
      been suggested, the underlying mechanisms remain to be elucidated. Sialic acid
      acetylesterase (SIAE) plays a crucial role in regulating the threshold of
      autoantibody production of B-cells and the defective variants of SIAE are
      associated with an increased risk of various autoimmune diseases such as type 1
      diabetes (T1DM). To explore the link between anti-PIT-1 antibody syndrome and
      SIAE, we analyzed SIAE gene in 3 patients with anti-PIT-1 antibody syndrome and
      200 healthy control subjects, and compared the prevalence of single nucleotide
      polymorphisms. Intriguingly, we found A467V SIAE variants (c.1400C>T, rs7941523)
      in a heterozygous state in all the patients with anti-PIT-1 antibody syndrome,
      while we detected in 6 % of control subjects, in which the prevalence was
      significantly increased in the patients (P<0.0005). Considering the physiological
      function of SIAE and the clinical features of anti-PIT-1 antibody syndrome,
      present data imply a novel aspect of the pathogenesis in this disease. 

PMID- 24748457
TI  - Increase of beta cell mass by beta cell replication, but not neogenesis, in the
      maternal pancreas in mice.
AB  - Strategies for increasing functional beta cell mass are effective for diabetes
      therapy. Although controversy remains on the existence of facultative beta cell
      progenitors in the adult pancreas, most evidence does not support such a
      possibility. One of the greatest physiological increases in beta cells has been
      detected in the maternal pancreas during pregnancy, following neonatal period and
      in the setting of insulin resistance. However, no systematical analysis on the
      beta cell growth in this period has been ever performed. Here we analyzed beta
      cell replication by quantifying BrdU incorporated beta cells at different time
      points in the pregnant mice. Similarly, we evaluated the possible involvement of
      beta cell neogenesis (differentiation from progenitor cells) by analyzing
      expression of Neurog3, a key determinant of pancreatic endocrine cell neogenesis
      during embryogenesis, in the exocrine pancreas. We found a dynamic increase in
      beta cell replication, but failed to detect beta cell neogenesis, demonstrating
      that beta cell growth in the maternal pancreas during pregnancy is predominantly
      attributable to beta cell replication, rather than beta cell neogenesis. 

PMID- 24748458
TI  - Competition between phytoplankton and bacteria: exclusion and coexistence.
AB  - Resource-based competition between microorganisms species in continuous culture
      has been studied extensively both experimentally and theoretically, mostly for
      bacteria through Monod and Contois "constant yield" models, or for phytoplankton
      through the Droop "variable yield" models. For homogeneous populations of N
      bacterial species (Monod) or N phytoplanktonic species (Droop), with one limiting
      substrate and under constant controls, the theoretical studies indicated that
      competitive exclusion occurs: only one species wins the competition and displaces
      all the others (Armstrong and McGehee in Am Nat 115:151, 1980; Hsu and Hsu in
      SIAM J Appl Math 68:1600-1617, 2008). The winning species expected from theory is
      the one with the lowest "substrate subsistence concentration" s([star]), such
      that its corresponding equilibrium growth rate is equal to the dilution rate D.
      This theoretical result was validated experimentally with phytoplankton (Tilman
      and Sterner in Oecologia 61(2):197-200, 1984) and bacteria (Hansen and Hubell in
      Science 207(4438):1491-1493, 1980), and observed in a lake with microalgae
      (Tilman in Ecology 58(22):338-348, 1977). On the contrary for aggregating
      bacterial species described by a Contois model, theory predicts coexistence
      between several species (Grognard et al. in Discrete Contin Dyn Syst Ser B
      8(1):73-93, 2007). In this paper we present a generalization of these results by
      studying a competition between three different types of microorganisms:
      planktonic (or free) bacteria (represented by a generalized Monod model),
      aggregating bacteria (represented by a Contois model) and free phytoplankton
      (represented by a Droop model). We prove that the outcome of the competition is a
      coexistence between several aggregating bacterial species with a free species of
      bacteria or phytoplankton, all the other free species being washed out. This
      demonstration is based mainly on the study of the substrate concentration's
      evolution caused by competition; it converges towards the lowest subsistence
      concentration s([star]), leading to three different types of competition
      outcomes: (1) the best free bacteria or phytoplankton competitor excludes all
      other species; (2) only some aggregating bacterial species coexist in the
      chemostat; (3) A coexistence between the single best free species, with one or
      several aggregating species.

PMID- 24748459
TI  - Medical services at ultra-endurance foot races in remote environments: medical
      issues and consensus guidelines.
AB  - An increasing participation in ultra-endurance foot races is cause for greater
      need to ensure the presence of appropriate medical care at these events. Unique
      medical challenges result from the extreme physical demands these events place on
      participants, the often remote settings spanning broad geographical areas, and
      the potential for extremes in weather conditions and various environmental
      hazards. Medical issues in these events can adversely affect race performance,
      and there is the potential for the presentation of life-threatening issues such
      as exercise-associated hyponatremia, severe altitude illnesses, and major trauma
      from falls or animal attacks. Organization of a medical support system for ultra
      endurance foot races starts with a determination of the level of medical support
      that is appropriate and feasible for the event. Once that is defined, various
      legal considerations and organizational issues must be addressed, and medical
      guidelines and protocols should be developed. While there is no specific or
      universal standard of medical care for ultra-endurance foot races since a variety
      of factors determine the level and type of medical services that are appropriate
      and feasible, the minimum level of services that each event should have in place
      is a plan for emergency transport of injured or ill participants, pacers,
      spectators and event personnel to local medical facilities. 

PMID- 24748460
TI  - Applied sport science of rugby league.
AB  - Rugby league is a team sport in which players engage in repeated high-intensity
      exercise involving frequent collisions. Recent research, much of which has
      involved global positioning system (GPS) technology, has provided coaches and
      sport scientists with a deeper understanding of match demands, particularly at
      the elite level. This has allowed for the development of training programmes that
      prepare players for the most intense contact and running demands likely to be
      experienced in competition. At the elite level, rugby league players have well
      developed aerobic and anaerobic endurance, muscular strength and power, reactive
      agility, and speed. Upper- and lower-body strength and aerobic power are
      associated with a broad range of technical and sport-specific skills, in addition
      to a lower risk of injury. Significant muscle damage (as estimated from creatine
      kinase concentrations) and fatigue occurs as a result of match-play; while muscle
      function and perceptual fatigue generally return to baseline 48 h following
      competition, increases in plasma concentrations of creatine kinase can last for
      up to 5 days post-match. Well-developed physical qualities may minimise post
      match fatigue and facilitate recovery. Ultimately, the literature highlights that
      players require a broad range of physical and technical skills developed through
      specific training. This review evaluates the demands of the modern game, drawing
      on research that has used GPS technology. These findings highlight that preparing
      players based on the average demands of competition is likely to leave them
      underprepared for the most demanding passages of play. As such, coaches should
      incorporate drills that replicate the most intense repeated high-intensity
      demands of competition in order to prepare players for the worst-case scenarios
      expected during match-play. 

PMID- 24748461
TI  - Alcohol: impact on sports performance and recovery in male athletes.
AB  - Alcohol is the most commonly used recreational drug globally and its consumption,
      often in large volume, is deeply embedded in many aspects of Western society.
      Indeed, athletes are not exempt from the influence alcohol has on society; they
      often consume greater volumes of alcohol through bingeing behaviour compared with
      the general population, yet it is often expected and recommended that athletes
      abstain from alcohol to avoid the negative impact this drug may have on recovery
      and sporting performance. While this recommendation may seem sensible, the impact
      alcohol has on recovery and sports performance is complicated and depends on many
      factors, including the timing of alcohol consumption post-exercise, recovery time
      required before recommencing training/competition, injury status and dose of
      alcohol being consumed. In general, acute alcohol consumption, at the levels
      often consumed by athletes, may negatively alter normal immunoendocrine function,
      blood flow and protein synthesis so that recovery from skeletal muscle injury may
      be impaired. Other factors related to recovery, such as rehydration and glycogen
      resynthesis, may be affected to a lesser extent. Those responsible for the
      wellbeing of athletes, including the athlete themselves, should carefully monitor
      habitual alcohol consumption so that the generic negative health and social
      outcomes associated with heavy alcohol use are avoided. Additionally, if athletes
      are to consume alcohol after sport/exercise, a dose of approximately 0.5 g/kg
      body weight is unlikely to impact most aspects of recovery and may therefore be
      recommended if alcohol is to be consumed during this period.

PMID- 24748463
TI  - Association of miRNA-122-binding site polymorphism at the interleukin-1 alpha
      gene and its interaction with hepatitis B virus mutations with hepatocellular
      carcinoma risk.
AB  - This study was designed to investigate the contribution of miRNA-122-binding site
      polymorphism at the IL-1A gene and its multiplicative interactions with hepatitis
      B virus (HBV) mutations in the risk of hepatocellular carcinoma (HCC). A total of
      1021 healthy controls, 302 HBV surface antigen (HBsAg) seroclearance subjects,
      and 2011 HBsAg-positive subjects (including 1021 HCC patients) were enrolled in
      this study. Quantitative PCR was used to genotype rs3783553. HBV mutations were
      determined by direct sequencing. Multivariate logistic regression analyses were
      performed to test the associations of rs3783553, mutations, and their
      interactions with the risk of HCC. No significant association was found between
      rs3783553 and the risk of HCC among healthy controls, HBsAg seroclearance
      subjects, HBsAg-positive subjects without HCC, and all controls. Additionally,
      rs3783553 was not significantly associated with chronic HBV infection, liver
      cirrhosis, HBV e antigen seroconversion, abnormal alanine aminotransferase, and
      high viral load (> 10(4) copies/ml). However, the TTCA insertion allele of
      rs3783553 was significantly associated with an increased frequency of HBV C7A
      mutation compared with homozygous TTCA deletion carriers [(del/ins + ins/ins) vs.
      del/del, adjusted odds ratio (OR)= 1.48, 95% confidence interval (CI)= 1.09-2.02,
      P = 0.013]. Multiplicative interaction of rs3783553 with HBV preS deletion
      significantly reduced the risk of HCC in males, with an adjusted OR of 0.64 (95%
      CI = 0.42-0.98; P = 0.041) after age and HBV genotype were adjusted. Although
      rs3783553 did not significantly affect genetic susceptibility to HBV-related HCC,
      its variant allele may predispose the host to selecting HBV C7A mutation during
      evolution and significantly reduce the risk of HCC caused by HBV preS deletion.
      This study provides an insight into the complex host-virus interaction in HBV
      induced hepatocarcinogenesis and is helpful in determining HBsAg-positive
      subjects who are likely to develop HCC. 

PMID- 24748464
TI  - Peak shift in honey bee olfactory learning.
AB  - If animals are trained with two similar stimuli such that one is rewarding (S+)
      and one punishing (S-), then following training animals show a greatest
      preference not for the S+, but for a novel stimulus that is slightly more
      different from the S- than the S+ is. This peak shift phenomenon has been widely
      reported for vertebrates and has recently been demonstrated for bumblebees and
      honey bees. To explore the nature of peak shift in invertebrates further, here we
      examined the properties of peak shift in honey bees trained in a free-flight
      olfactory learning assay. Hexanal and heptanol were mixed in different ratios to
      create a continuum of odour stimuli. Bees were trained to artificial flowers such
      that one odour mixture was rewarded with 2 molar sucrose (S+), and one punished
      with distasteful quinine (S-). After training, bees were given a non-rewarded
      preference test with five different mixtures of hexanal and heptanol. Following
      training bees' maximal preference was for an odour mixture slightly more distinct
      from the S- than the trained S+. This effect was not seen if bees were initially
      trained with two distinct odours, replicating the classic features of peak shift
      reported for vertebrates. We propose a conceptual model of how peak shift might
      occur in honey bees. We argue that peak shift does not require any higher level
      of processing than the known olfactory learning circuitry of the bee brain and
      suggest that peak shift is a very general feature of discrimination learning. 

PMID- 24748462
TI  - Generation and repair of AID-initiated DNA lesions in B lymphocytes.
AB  - Activation-induced deaminase (AID) initiates the secondary antibody
      diversification process in B lymphocytes. In mammalian B cells, this process
      includes somatic hypermutation (SHM) and class switch recombination (CSR), both
      of which require AID. AID induces U:G mismatch lesions in DNA that are
      subsequently converted into point mutations or DNA double stranded breaks during
      SHM/CSR. In a physiological context, AID targets immunoglobulin (Ig) loci to
      mediate SHM/CSR. However, recent studies reveal genome-wide access of AID to
      numerous non-Ig loci. Thus, AID poses a threat to the genome of B cells if AID
      initiated DNA lesions cannot be properly repaired. In this review, we focus on
      the molecular mechanisms that regulate the specificity of AID targeting and the
      repair pathways responsible for processing AID-initiated DNA lesions. 

PMID- 24748465
TI  - Sequential combination of robot-assisted therapy and constraint-induced therapy
      in stroke rehabilitation: a randomized controlled trial.
AB  - Robot-assisted therapy (RT) and constraint-induced therapy (CIT) both show great
      promise to improve stroke rehabilitation outcomes. Although the respective
      treatment efficacy of RT and CIT has been validated, the additive effects of RT
      combined with CIT remain unknown. This study investigated the treatment effects
      of RT in sequential combination with a distributed form of CIT (RT + dCIT)
      compared with RT and conventional rehabilitation (CR). Forty-eight patients with
      stroke were enrolled and randomized to receive one of the three interventions for
      4 weeks. Primary outcomes assessed the changes of motor impairment and motor
      function on the Fugl-Meyer Assessment (FMA) and Wolf Motor Function Test (WMFT).
      Secondary outcomes, including the Motor Activity Log (MAL) and accelerometers,
      examined functional performance during daily activities. The three treatment
      groups improved significantly on most primary and secondary outcomes over time.
      The combined RT + dCIT group exhibited significantly greater improvement on the
      FMA and functional ability subscale of the WMFT than the RT and CR groups. The
      improvements on the MAL and accelerometers were not significantly different among
      the three groups. RT in sequential combination with CIT led to additive effects
      on participants' motor ability and functional ability to perform motor tasks
      after stroke, which support that combined therapy can be an effective means to
      intensify outcomes. Further research investigating the potential long-term
      effects of combination therapy, especially on real-life performance, would be
      valuable.

PMID- 24748466
TI  - A case of vertebral artery duplication at the level of atlas: anatomical
      description.
AB  - PURPOSE: To present case of vertebral artery duplication surrounding the
      posterior arch of atlas. METHODS: The vertebral artery variation was encountered
      during dissection of specimen from the body of a 62-year-old man. RESULTS: The
      vertebral artery formed a circle located extraduraly, surrounding the posterior
      arch of atlas vertebra. Topography and morphometry of the finding is described.
      Embryology and clinical significance based on literature review are discussed.
      CONCLUSIONS: Precise diagnostic imaging is necessary before surgical
      interventions at the level of cranio-spinal junction in order to avoid conflict
      with rare vascular variations.

PMID- 24748467
TI  - Probing the impact of GFP tagging on Robo1-heparin interaction.
AB  - Green fluorescent proteins (GFPs) and their derivatives are widely used as
      markers to visualize cells, protein localizations in in vitro and in vivo
      studies. The use of GFP fusion protein for visualization is generally thought to
      have negligible effects on cellular function. However, a number of reports
      suggest that the use of GFP may impact the biological activity of these proteins.
      Heparin is a glycosaminoglycan (GAG) that interacts with a number of proteins
      mediating diverse patho-physiological processes. In the heparin-based interactome
      studies, heparin-binding proteins are often prepared as GFP fusion proteins. In
      this report, we use surface plasmon resonance (SPR) spectroscopy to study the
      impact of the GFP tagging on the binding interaction between heparin and a
      heparin-binding protein, the Roundabout homolog 1 (Robo1). SPR reveals that
      heparin binds with higher affinity to Robo1 than GFP-tagged Robo1 and through a
      different kinetic mechanism. A conformational change is observed in the heparin
      Robo1 interaction, but not in the heparin-Robo1-GFP interaction. Furthermore the
      GFP-tagged Robo1 requires a shorter (hexasaccharide) than the tag-free Robo1
      (octadecasaccharide). These data demonstrate that GFP tagging can reduce the
      binding affinity of Robo1 to heparin and hinder heparin binding-induced Robo1
      conformation change.

PMID- 24748468
TI  - Occurrence of novel Cu(2+)-dependent sialic acid-specific lectin, on the outer
      surface of mature caprine spermatozoa.
AB  - Effects of several bivalent metal ions on the autoagglutination event in mature
      caprine epididymal sperm cells have been investigated using a chemically defined
      medium. This study demonstrates for the first time that Copper (Cu(2+)) ion (300
      MUM) has high specificity for autoagglutination of mature cauda-epididymal sperm.
      Head-to-head interaction of the male gametes is responsible for this event.
      Studies on the effect of various sugars reveal that the autoagglutinated cells
      can be dissociated specifically with neutralized sialic acid (50 mM), which also
      inhibits the sperm cell autoagglutination phenomenon. Blood serum protein fetuin,
      that contains terminal sialic acid residue, showed high efficacy for inhibiting
      this autoagglutination event at 4 MUM concentration. However, asialofetuin is not
      capable of inhibiting this Cu(2+)-dependent cellular event. Mature sperm cells
      bound with caprine erythrocytes at their head region in presence of Cu(2+) ion.
      The purified sperm membrane fraction isolated by aqueous two phase polymer method
      showed high efficacy to agglutinate erythrocytes. These sperm-erythrocyte
      interactions as well as sperm membrane induced haemagglutination were strongly
      blocked by neutralized sialic acid (50 mM). The results confirm the occurrence of
      unique Cu(2+) dependent, sialic acid-specific lectin on the outer surface of a
      mammalian cell using caprine sperm as the model. The observed Cu(2+)-mediated
      cellular autoagglutination is caused by the interaction of the cell surface
      lectin with the lectin receptor on the surface of the neighboring homologous
      cell.

PMID- 24748469
TI  - The detection of T-Nos, a genetic element present in GMOs, by cross-priming
      isothermal amplification with real-time fluorescence.
AB  - An isothermal cross-priming amplification (CPA) assay for Agrobacterium
      tumefaciens nopaline synthase terminator (T-Nos) was established and investigated
      in this work. A set of six specific primers, recognizing eight distinct regions
      on the T-Nos sequence, was designed. The CPA assay was performed at a constant
      temperature, 63  degrees C, and detected by real-time fluorescence. The results
      indicated that real-time fluorescent CPA had high specificity, and the limit of
      detection was 1.06 * 10(3) copies of rice genomic DNA, which could be detected in
      40 min. Comparison of real-time fluorescent CPA and conventional polymerase chain
      reaction (PCR) was also performed. Results revealed that real-time fluorescent
      CPA had a comparable sensitivity to conventional real-time PCR and had taken a
      shorter time. In addition, different contents of genetically modified (GM)
      contaminated rice seed powder samples were detected for practical application.
      The result showed real-time fluorescent CPA could detect 0.5 % GM-contaminated
      samples at least, and the whole reaction could be finished in 35 min. Real-time
      fluorescent CPA is sensitive enough to monitor labeling systems and provides an
      attractive method for the detection of GMO.

PMID- 24748471
TI  - Low vitamin D level is not associated with increased incidence of rheumatoid
      arthritis.
AB  - To evaluate the association of vitamin D level with incident rheumatoid arthritis
      (RA) in a patient population using electronic health records (EHR). Case-control
      study with data extracted from EHR from 1/1/2001 to 12/31/2012 in the Geisinger
      Health System (GHS). Incident RA was defined as International Classification of
      Disease-9 code 714.0 twice by a GHS rheumatologist. Patients were identified at
      time of RA diagnoses and were matched 1:5 for age and gender with non-RA
      controls. Vitamin D levels were identified and extracted prior to RA diagnosis.
      The subjects were followed retrospectively with regard to their vitamin D levels;
      the most recent value of vitamin D prior to the RA diagnosis was used in the
      analysis. Vitamin D levels were treated both as continuous and categorical with
      two different cutoff values, 30 and 20 ng/ml. The association between vitamin D
      and RA was presented as the odds ratios with 95 % confidence intervals (OR, 95 %
      CI) from a conditional logistic regression model adjusting for obesity and
      smoking status. A total of 270 patients with incident RA and 1,341 matched
      controls were identified. The RA patients were 83.3 % female with median age at
      RA diagnosis of 62 years. The adjusted OR (95 % CI) for the association of
      vitamin D levels with incident RA compared with controls was 1.00 (0.99, 1.01),
      0.98 (0.75, 1.29) and 1.12 (0.80, 1.57) for continuous, <30 and <20 ng/ml vitamin
      D levels, respectively. Subgroup analysis according to gender or rheumatoid
      factor positivity yielded similar results. In this patient population, vitamin D
      levels were not associated with the development of RA.

PMID- 24748470
TI  - IDH1 mutation and MGMT methylation status predict survival in patients with
      anaplastic astrocytoma treated with temozolomide-based chemoradiotherapy.
AB  - Several molecular markers have been proposed as predictors of outcome in patients
      with high grade gliomas. We report a retrospective multicenter study of 97
      consecutive adult patients with anaplastic astrocytoma (AA) treated with
      radiation therapy (RT) plus concomitant and adjuvant temozolomide (TMZ) between
      October 2004 and March 2012. Correlations between the isocitrate dehydrogenase 1
      (IDH1) mutation and O-6-methylguanine-DNA methyltransferase (MGMT) promoter
      methylation with survival outcomes have been analyzed. At a median follow-up time
      of 46 months (range 12-89 months), median and 5-year overall survival rates were
      50.5 months (95 % CI, 37.8-63.2) and 38% (95 % CI, 25.7-50.7%), and median and 5
      year progression-free survival rates were 36 months (95% CI, 28.5-44.0) and 22 %
      (95 % CI, 10-34%), respectively. IDH1 mutation and MGMT promoter methylation were
      present in 54 and 60% of evaluable patients, respectively. Multivariate Cox
      proportional hazards regression analysis showed that IDH1 mutation (P = 0.001),
      MGMT methylation (P = 0.01), age < 50 years (P = 0.02), and extent of resection
      (P = 0.04) were significantly associated with longer survival. Our study confirms
      the favorable prognostic value of IDH1 mutation and MGMT methylation in patients
      with AA treated with RT plus concomitant and adjuvant TMZ. The superiority of
      combined radiochemotherapy over other treatment modalities remains to be
      demonstrated.

PMID- 24748472
TI  - Influences of gender on complication rate and outcome after Roux-en-Y gastric
      bypass: data analysis of more than 10,000 operations from the German Bariatric
      Surgery Registry.
AB  - BACKGROUND: Since 1 January 2005, bariatric surgery has been monitored in
      Germany. All related data are registered prospectively in cooperation with the
      Institute of Quality Assurance in Surgery at the Otto-von-Guericke University
      Magdeburg. METHODS: Data collection regarding obesity and metabolic surgery was
      started in an online database in 2005. Follow-up data are collected once a year.
      Participation in the quality assurance study is voluntary. RESULTS: Since 2005,
      10,330 Roux-en-Y gastric bypass (RYGB) procedures have been performed in Germany.
      In total, 8,013 patients were female and 2,317 were male. Male patients suffered
      significantly more comorbidities than female patients. The men also had higher
      body mass indexes (BMIs) and ages than the women at the time of operation. Data
      on the gender-specific aspects of RYGB from the Nationwide Survey of Bariatric
      Surgery in Germany (GBSR) showed a significant difference in anastomotic
      insufficiency at the gastro-entero-anastomosis. The leakage rate was 2.37 %
      (55/2,317) in men and 1.68 % (135/8,013) in women. Additionally, specific
      complication and mortality rates were significantly higher in male than in female
      patients. CONCLUSIONS: Metabolic and obesity surgery is becoming increasingly
      popular in Germany. Data from the GBSR show significant differences in
      preoperative comorbidities and postoperative complication and mortality rates
      between male and female patients. There is a need for further evaluation of
      gender-specific aspects to optimize patient selection and reduce specific
      postoperative complications.

PMID- 24748473
TI  - Are there risk factors that increase the rate of staple line leakage in patients
      undergoing primary sleeve gastrectomy for morbid obesity?
AB  - BACKGROUND: Laparoscopic sleeve gastrectomy (LSG) is currently being performed
      with increasing frequency worldwide. It offers an excellent weight loss and
      resolution of comorbidities in the short term with a very low incidence of
      complications. However, the ever present risk of a staple line leak is still a
      major concern. METHODS: Since 2005, data from obese patients that undergo
      bariatric procedures in Germany are prospectively registered in an online
      database and analyzed at the Institute of Quality Assurance in Surgical Medicine.
      For the current analysis, all patients that had undergone primary sleeve
      gastrectomy for morbid obesity within a 7-year period were considered. RESULTS:
      Using the GBSR, data from 5.400 LSGs were considered for analysis. Staple line
      leak rate decreased during the study period from 6.5 to 1.4 %. Male gender,
      higher BMI, concomitant sleep apnea, conversion to laparotomy, longer operation
      time, use of both buttresses and oversewing, and the occurrence of intraoperative
      complications were associated with a significantly higher leakage rate. On
      multivariate analysis, operation time and year of procedure only had a
      significant impact on staple line leak rate. CONCLUSIONS: The results of the
      current study demonstrated that there are factors that increase the risk of a
      leakage which would enable surgeons to define risk groups, to more carefully
      select patients, and to offer a closer follow-up during the postoperative course
      with early recognition and adequate treatment. All future efforts should be
      focused on a further reduction of serious complications to make the LSG a widely
      accepted and safer procedure.

PMID- 24748474
TI  - Changes in nutrients and food groups intake following laparoscopic Roux-en-Y
      gastric bypass (RYGB).
AB  - BACKGROUND: Serial changes in dietary intake, including specific food groups and
      nutrients during the first year following Roux-en-Y gastric bypass (RYGB) are of
      interest due to surgically induced alterations in meal size, food intolerances
      present after surgery, and potential nutrient deficiencies. To help improve the
      nutritional health of surgical patients, this study's purpose was to examine
      changes in macro- and micronutrients, food groups, and selected foods during 12
      months of follow-up in post-RYGB individuals. METHODS: RYGB patients (n = 17)
      completed 4-day food records at baseline (prior to surgery) and then at 3 weeks,
      3 months, 6 months, and 12 months after surgery. Mean daily intake was determined
      at each time for energy intake, macro- and micronutrients, food groups, and
      selected foods in targeted food groups. RESULTS: A dramatic decrease in mean (+/-
      SEM) daily energy intake occurred--2,150 +/- 165 kcal at baseline vs. 649 +/- 40
      kcal at 3 weeks; energy intake continually increased to a high of 1,307 +/- 129
      kcal by 12 months. More than 50 % of patients had low intake of vitamins D, E, C,
      folate, and calcium, magnesium, and potassium at 12 months. Servings from
      vegetables, grains, fats, and sweetened beverages were lower, whereas, meats,
      dairy, fruits, and sweets showed only small, transient changes following surgery.
      CONCLUSIONS: The reduction in energy intake following RYGB is from selected food
      groups and not solely a reduction in portion sizes across the diet. The lower
      intake of micronutrients indicates potential risk for deficiencies unless
      supplements are used. These findings can help in the clinical management of
      surgical patients to improve nutritional health.

PMID- 24748475
TI  - Vitamin D supplementation efficacy: sleeve gastrectomy versus gastric bypass
      surgery.
AB  - BACKGROUND: Vitamin D deficiency is common with bariatric surgery, and few
      prospective studies comparing different surgical procedures have evaluated
      appropriate vitamin D supplementation levels. Therefore, vitamin D3 and calcium
      supplementation were evaluated following gastric bypass and sleeve gastrectomy.
      METHODS: Women consumed 2,000 international units (IU) of vitamin D3 and 1,500 mg
      calcium citrate daily for 3 months following gastric bypass (n=11) and sleeve
      gastrectomy (n=12). Height, weight, body mass index (BMI), serum 25
      hydroxyvitamin D [25(OH)D], and serum PTH concentrations were measured
      preoperatively and at 3 months. Wilcoxon signed rank analyses compared body
      weight parameters, serum 25(OH)D and PTH concentrations, and dietary intakes of
      vitamin D and calcium preoperatively and at 3 months. Vitamin D deficiency was
      defined as a serum 25(OH)D concentration <20 ng/mL (50 nmol/L). RESULTS: Vitamin
      D deficiency decreased from 60.6 % preoperatively to 26.1 % after 3 months
      (P<0.005). Serum 25(OH)D concentrations increased an average of 8 ng/mL
      (P<0.001), and PTH concentrations decreased an average of 9 ng/L, although
      reductions were not significant. Overall, the response to supplementation
      following gastric bypass and sleeve gastrectomy did not differ. CONCLUSIONS:
      Reduced food intake increased the risk of vitamin D deficiency following
      bariatric surgery. However, daily supplementation with 2,000 IU of vitamin D3 and
      1,500 mg calcium citrate significantly increased 25(OH)D concentrations and
      reduced the percent of women who were vitamin D deficient. Although serum 25(OH)D
      concentrations did not reach levels associated with detrimental health effects,
      several women remained vitamin D deficient and more aggressive supplementation
      may be indicated.

PMID- 24748476
TI  - Hsp70 regulates the doxorubicin-mediated heart failure in Hsp70-transgenic mice.
AB  - The aim of this study was to investigate the potential protective effect of the
      Hsp70 protein in the cardiac dysfunction induced by doxorubicin (DOX) and the
      mechanisms of its action. For this purpose, we used both wild-type mice (F1/F1)
      and Hsp70-transgenic mice (Tg/Tg) overexpressing human HSP70. Both types were
      subjected to chronic DOX administration (3 mg/kg intraperitoneally every week for
      10 weeks, with an interval from weeks 4 to 6). Primary cell cultures isolated
      from embryos of these mice were also studied. During DOX administration, the
      mortality rate as well as weight reduction were lower in Tg/Tg compared to F1/F1
      mice (P < 0.05). In vivo cardiac function assessment by transthoracic
      echocardiography showed that the reduction in left ventricular systolic function
      observed after DOX administration was lower in Tg/Tg mice (P < 0.05). The study
      in primary embryonic cell lines showed that the apoptosis after incubation with
      DOX was reduced in cells overexpressing Hsp70 (Tg/Tg), while the apoptotic
      pathway that was activated by DOX administration involved activated protein
      factors such as p53, Bax, caspase-9, caspase-3, and PARP-1. In myocardial protein
      extracts from identical mice with DOX-induced heart failure, the particular
      activated apoptotic pathway was confirmed, while the presence of Hsp70 appeared
      to inhibit the apoptotic pathway upstream of the p53 activation. Our results, in
      this DOX-induced heart failure model, indicate that Hsp70 overexpression in Tg/Tg
      transgenic mice provides protection from myocardial damage via an Hsp70-block in
      p53 activation, thus reducing the subsequent apoptotic mechanism.

PMID- 24748477
TI  - Remifentanil attenuates lipopolysaccharide-induced acute lung injury by
      downregulating the NF-kappaB signaling pathway.
AB  - Remifentanil significantly represses cell immune responses and influences
      neutrophil migration through endothelial cell monolayers. The present study
      determines the beneficial effects of remifentanil and the mechanisms by which it
      attenuates lipopolysaccharide (LPS)-induced acute lung injury (ALI). Rats were
      intratracheally instilled with 2 mg/kg LPS to induce ALI. Results showed that
      remifentanil could resolve lung injury, as evidenced by remarkable decreases in
      lung edema (wet-to-dry weight ratio), neutrophil infiltration (myeloperoxidase
      activity), and pulmonary permeability [total number of cells and protein
      concentrations in bronchoalveolar lavage fluid (BALF)]. Remifentanil also
      attenuated the concentrations of proinflammatory cytokines tumor necrosis factor
      alpha, interleukin-1beta, and interleukin-6 in BALF, as well as effectively
      repressed the activation of nuclear factor-kappaB (NF-kappaB), which has been
      associated with the inhibition of IkappaBalpha degradation.These results suggest
      that remifentanil may be a suitable treatment for LPS-induced ALI. Remifentanil
      exerts beneficial effects on the inhibition of proinflammatory cytokine
      production by downregulating the NF-kappaB pathway.

PMID- 24748478
TI  - Intra-arterial thrombolysis in a young patient with cocaine-associated stroke.

PMID- 24748479
TI  - Protective effect of preserved bladder-filling sensation on upper urinary tract
      in patients with spinal cord injury.
AB  - In this study the possible preventive effect of bladder-filling sensation (BFS)
      on upper urinary tract deterioration (UUTD) in spinal cord injury (SCI) patients
      was investigated. Eighty-four (60 males, 24 females) patients with SCI who
      underwent neurourological assessment and urodynamic examinations because of
      neurogenic lower urinary tract dysfunction and were prescribed appropriate
      bladder management and were under follow-up and whose disease duration was at
      least 3 years were included in the study. Bladder-filling sensation was
      categorised as "absent", "partially preserved" or "preserved", and as "normal"
      (preserved) and "abnormal" (partially preserved, absent). Presence of
      hydronephrosis, renal stones, and chronic pyelonephritis in any renal USG or IVP
      performed during the follow-up period were accepted as criteria of UUTD. The
      frequencies of UUTD for BFS subgroups were determined and compared. Mean age and
      mean disease duration were 38.4 +/- 13.0 years and 72.2 +/- 36.2 months. The
      frequency of UUTD was 31/84 (36.9 %) in the study population. The frequencies of
      UUTD were 0/8 (0 %), 22/53 (41.5 %) and 9/23 (39.1 %) for "preserved" "partially
      preserved" and "absent" BFS subgroups, respectively (p = 0.074). There was a
      statistically significant difference between normal BFS [0/8 (0 %)] and abnormal
      BFS [31/76 (40.8 %)] subgroups (p = 0.024). According to the results of our study
      preserved (normal) bladder-filling sensation has protective effect on upper
      urinary tract in patients with SCI.

PMID- 24748480
TI  - Proconvulsant effects of estriol, the third estrogen, in the mouse PTZ-kindling
      model.
AB  - The effect of estriol, the third estrogen, was evaluated for its effect on
      pentylenetetrazole (PTZ)-kindling model of epileptogenesis in mice followed by
      evaluation on kindling-induced changes in cognitive and motor functions. Kindling
      was induced by once every 2 days treatment with PTZ (25 mg/kg, i.p.) for 5 weeks.
      The seizure severity during induction of kindling and percentage incidence of
      animals kindled at the end of 5 weeks was recorded. Motor function was assessed
      using a grip strength meter while spatial memory was assessed in a cross maze.
      Estriol (0.005 and 0.01 mg/kg i.p.) reduced the time for induction of kindling
      from 5 weeks to 3 and 2 weeks for male and female mice respectively and enhanced
      the percentage incidence of seizures. Clomiphene (0.9 mg/kg i.p.) delayed the
      development of kindling and produced anticonvulsant effects. It also partially
      reversed the proconvulsant effects of estriol. On grip strength test and
      spontaneous alternation behaviour, a significant decline was observed in kindled
      mice which was further reduced by pre-treatment with estriol. Both clomiphene and
      diazepam were unable to reverse the reduced GS of PTZ-kindled mice but enhanced
      the percentage alternation of such animals. The study shows that estriol has
      powerful proconvulsant effects. Its administration in hormone replacement therapy
      or other indications, thus, requires careful monitoring in patients susceptible
      to epileptic seizures. The anticonvulsant effects of clomiphene requires further
      investigations.

PMID- 24748481
TI  - Effect of desipramine and citalopram treatment on forced swimming test-induced
      changes in cocaine- and amphetamine-regulated transcript (CART) immunoreactivity
      in mice.
AB  - Recent study demonstrates antidepressant-like effect of cocaine- and amphetamine
      regulated transcript (CART) in the forced swimming test (FST), but less is known
      about whether antidepressant treatments alter levels of CART immunoreactivity
      (CART-IR) in the FST. To explore this possibility, we assessed the treatment
      effects of desipramine and citalopram, which inhibit the reuptake of
      norepinephrine and serotonin into the presynaptic terminals, respectively, on
      changes in levels of CART-IR before and after the test swim in mouse brain.
      Levels of CART-IR in the nucleus accumbens shell (AcbSh), dorsal bed nucleus of
      the stria terminalis (dBNST), and hypothalamic paraventricular nucleus (PVN) were
      significantly increased before the test swim by desipramine and citalopram
      treatments. This increase in CART-IR in the AcbSh, dBNST, and PVN before the test
      swim remained elevated by desipramine treatment after the test swim, but this
      increase in these brain areas returned to near control levels after test swim by
      citalopram treatment. Citalopram, but not desipramine, treatment increased levels
      of CART-IR in the central nucleus of the amygdala (CeA) and the locus ceruleus
      (LC) before the test swim, and this increase was returned to control levels after
      the test swim in the CeA, but not in the LC. These results suggest common and
      distinct regulation of CART by desipramine and citalopram treatments in the FST
      and raise the possibility that CART in the AcbSh, dBNST, and CeA may be involved
      in antidepressant-like effect in the FST. 

PMID- 24748482
TI  - The spatial alignment effect in near and far space: a kinematic study.
AB  - The present experiment aimed at verifying whether the spatial alignment effect
      modifies kinematic parameters of pantomimed reaching-grasping of cups located at
      reachable and not reachable distance. The cup's handle could be oriented either
      to the right or to the left, thus inducing a grasp movement that could be either
      congruent or incongruent with the pantomime. The incongruence/congruence induced
      an increase/decrease in maximal finger aperture, which was observed when the cup
      was located near but not far from the body. This effect probably depended on
      influence of the size of the cup body on pantomime control when, in the
      incongruent condition, cup body was closer to the grasp hand as compared to the
      handle. Cup distance (near and far) influenced the pantomime even if it was
      actually executed in the same peripersonal space. Specifically, arm and hand
      temporal parameters were affected by actual cup distance as well as movement
      amplitudes. The results indicate that, when executing a reach-to-grasp pantomime,
      affordance related to the use of the object was instantiated (and in particular
      the spatial alignment effect became effective), but only when the object could be
      actually reached. Cup distance (extrinsic object property) influenced affordance,
      independently of the possibility to actually reach the target.

PMID- 24748484
TI  - Cytogenetic monitoring of nuclear workers occupationally exposed to ionising
      radiation.
AB  - Chromosome aberration (CA) analysis using Giemsa techniques was performed in
      blood lymphocytes of 84 nuclear workers with cumulative doses of 1-632 mSv during
      employment periods of 1-25 y. The control group comprised 82 healthy male donors.
      An estimated CA frequency in the total radiation-exposed group was significantly
      higher when compared with the controls (2.27 vs. 1.76 CA/100 cells, p < 0.05). CA
      analyses revealed no significant differences between workers with external gamma
      radiation exposure and the controls (1.60 vs. 1.76 CA/100 cells, p > 0.05).
      However, significant increase in the total CA frequency was determined in workers
      with additional internal exposure (2.54 CA/100 cells, p < 0.05) and those with
      registered neutron doses (2.95 CA/100 cells, p < 0.01). No correlation was found
      between CA frequency and occupational exposure dose. Borderline significant
      correlation was found between duration of employment and total CA (r = 0.218, p =
      0.046, Fig. 2) and chromosome-type aberration (r = 0.265, p = 0.015) frequency.

PMID- 24748483
TI  - Enhanced perceptions of control and predictability reduce motion-induced nausea
      and gastric dysrhythmia.
AB  - Nausea is a debilitating condition that is typically accompanied by gastric
      dysrhythmia. The enhancement of perceived control and predictability has
      generally been found to attenuate the physiological stress response. The aim of
      the present study was to test the effect of these psychosocial variables in the
      context of nausea, motion sickness, and gastric dysrhythmia. A 2x2, independent
      groups, factorial design was employed in which perceived control and
      predictability were each provided at high or low levels to 80 participants before
      exposure to a rotating optokinetic drum. Ratings of nausea were obtained
      throughout a 6-min baseline period and a 16-min drum rotation period. Noninvasive
      recordings of the electrical activity of the stomach called electrogastrograms
      were also obtained throughout the study. Nausea scores were significantly lower
      among participants with high control than among those with low control, and were
      significantly lower among participants with high predictability than among those
      with low predictability. Estimates of gastric dysrhythmia obtained from the EGG
      during drum rotation were significantly lower among participants with high
      predictability than among those with low predictability. A significant
      interaction effect of control and predictability on gastric dysrhythmia was also
      observed, such that high control was only effective for arresting the development
      of gastric dysrhythmia when high predictability was also available. Stronger
      perceptions of control and predictability may temper the development of nausea
      and gastric dysrhythmia during exposure to provocative motion. Psychosocial
      interventions in a variety of nausea contexts may represent an alternative means
      of symptom control. 

PMID- 24748485
TI  - Results of simultaneous radon and thoron measurements in 33 metropolitan areas of
      Canada.
AB  - Radon has been identified as the second leading cause of lung cancer after
      tobacco smoking. (222)Rn (radon gas) and (220)Rn (thoron gas) are the most common
      isotopes of radon. In order to assess thoron contribution to indoor radon and
      thoron exposure, a survey of residential radon and thoron concentrations was
      initiated in 2012 with ~4000 homes in the 33 census metropolitan areas of Canada.
      The survey confirmed that indoor radon and thoron concentrations are not
      correlated and that thoron concentrations cannot be predicted from widely
      available radon information. The results showed that thoron contribution to the
      radiation dose varied from 0.5 to 6% geographically. The study indicated that, on
      average, thoron contributes ~3% of the radiation dose due to indoor radon and
      thoron exposure in Canada. Even though the estimated average thoron concentration
      of 9 Bq m(-3) (population weighted) in Canada is low, the average radon
      concentration of 96 Bq m(-3) (population weighted) is more than double the
      worldwide average indoor radon concentration. It is clear that continued efforts
      are needed to further reduce the exposure and effectively reduce the number of
      lung cancers caused by radon.

PMID- 24748486
TI  - The effect on the radon diffusion coefficient of long-term exposure of waterproof
      membranes to various degradation agents.
AB  - Waterproofing, usually made of bitumen or polymers with various additives, is
      used to protect buildings mainly against dampness, but also against radon
      transported from the soil beneath the building. The radon diffusion coefficient
      is a material property which is considered to be strongly influenced by the inner
      structure (chemical composition, crystallinity) of a measured sample. We have
      used this parameter together with measurements of mechanical properties
      (hardness, tensile strength, elongation at break, etc.) and FTIR spectroscopy has
      been used in order to describe the changes in material properties induced by long
      term degradation. This paper summarizes the results of radon diffusion
      coefficient measurements of waterproof materials exposed to radon, soil bacteria,
      high temperature and combinations of these factors. We have discovered changes as
      high as 83 % have been discovered compared to virgin samples. 

PMID- 24748487
TI  - High-resolution mapping of 1D and 2D dose distributions using X-band electron
      paramagnetic resonance imaging.
AB  - Electron paramagnetic resonance imaging (EPRI) was performed to visualise 2D dose
      distributions of homogenously irradiated potassium dithionate tablets and to
      demonstrate determination of 1D dose profiles along the height of the tablets.
      Mathematical correction was applied for each relative dose profile in order to
      take into account the inhomogeneous response of the resonator using X-band EPRI.
      The dose profiles are presented with the spatial resolution of 0.6 mm from the
      acquired 2D images; this value is limited by pixel size, and 1D dose profiles
      from 1D imaging with spatial resolution of 0.3 mm limited by the intrinsic line
      width of potassium dithionate. In this paper, dose profiles from 2D reconstructed
      electron paramagnetic resonance (EPR) images using the Xepr software package by
      Bruker are focussed. The conclusion is that using potassium dithionate, the
      resolution 0.3 mm is sufficient for mapping steep dose gradients if the
      dosemeters are covering only +/-2 mm around the centre of the resonator. 

PMID- 24748488
TI  - Room temperature Q-band electron magnetic resonance study of radicals in X-ray
      irradiated l-threonine single crystals.
AB  - In the past, decennia radiation-induced radicals were successfully identified by
      electron magnetic resonance (EMR) in several solid-state amino acids and sugars.
      The authors present a room temperature (RT) EMR study of the stable radicals
      produced by X-ray-irradiation in the amino acid l-threonine (CH3CH(OH)CH(NH3
      (+))COO(-)). Its chemical structure is similar to that of the well-known
      dosimetric material l-alanine (CH3CH(NH3(+))COO(-)), and radiation defects in l
      threonine may straightforwardly be compared with the extensively studied l
      alanine radicals. The hyperfine coupling tensors of three different radicals were
      determined at RT using electron nuclear double resonance. These results indicate
      that the two most abundant radicals share the same basic structure
      CH3(*)C(OH)CH(NH3(+))COO(-), obtained by H-abstraction, but are stabilised in
      slightly different conformations. The third radical is most probably obtained by
      deamination (CH3CH(OH)(*)CHCOO(-)), similar in structure to the stable alanine
      radical.

PMID- 24748489
TI  - National radon programmes and policies: the RADPAR recommendations.
AB  - Results from epidemiological studies on lung cancer and radon exposure in
      dwellings and mines led to a significant revision of recommendations and
      regulations of international organisations, such as WHO, IAEA, Nordic Countries,
      European Commission. Within the European project RADPAR, scientists from 18
      institutions of 14 European countries worked together for 3 y (2009-12). Among
      other reports, a comprehensive booklet of recommendations was produced with the
      aim that they should be useful both for countries with a well-developed radon
      programme and for countries with little experience on radon issues. In this
      paper, the main RADPAR recommendations on radon programmes and policies are
      described and discussed. These recommendations should be very useful in preparing
      a national action plan, required by the recent Council Directive 2013/59/Euratom.

PMID- 24748491
TI  - Mean platelet volume and neutrophil-to-lymphocyte ratio in patients with Henoch
      Schonlein purpura.

PMID- 24748490
TI  - Soluble TNF receptors are produced at sites of inflammation and are inversely
      associated with self-reported symptoms (WOMAC) in knee osteoarthritis.
AB  - The aim of the study was to analyze the concentrations of sTNFR1 and sTNFR2 in
      both plasma and synovial fluid of patients with primary knee osteoarthritis (OA)
      and to determine their relationship to self-reported pain, stiffness and physical
      function. Twenty-seven patients with knee OA and 19 healthy subjects were
      enrolled in the study. The Western Ontario and McMaster University Osteoarthritis
      Index questionnaire was used to evaluate self-reported physical function, pain
      and stiffness. The sTNFR1 and sTNFR2 levels in the plasma and synovial fluid were
      measured by enzyme-linked immunosorbent assay. The sTNFR1 levels in synovial
      fluid of OA patients (2,587 +/- 66.12 pg/mL) were 2.5-fold higher than in
      corresponding blood samples and were 1.5-fold higher than in the plasma of
      healthy controls. The plasma sTNFR2 levels in the patients with knee OA were
      lower than in healthy controls (2,249 +/- 126.3 vs. 2,700 +/- 126.3 pg/mL, p <
      0.05), and sTNFR2 levels in synovial fluid of knee OA patients (2,021 +/- 107.0
      pg/mL) were lower than in the plasma of healthy controls. Synovial fluid sTNFR1
      levels were negatively correlated with pain and physical function self-reported
      (r s - 0.6785, p < 0.0001 and r s - 0.4194, p = 0.03, respectively). Synovial
      fluid sTNFR2 levels were negatively correlated with pain and joint stiffness (r s
      - 0.5433, p = 0.01 and r s - 0.4249, p = 0.02, respectively). The findings of
      this study demonstrated the presence of soluble receptors for TNF-alpha,
      particularly sTNFR1, in the synovial fluid of patients with primary knee OA and
      the relationship of these receptors with clinical parameters.

PMID- 24748492
TI  - Risk of venous thromboembolism in patients with idiopathic inflammatory myositis:
      a systematic review and meta-analysis.
AB  - We performed this meta-analysis to assess venous thromboembolism risk in patients
      with idiopathic inflammatory myositis (IIM). A comprehensive search was performed
      in MEDLINE, EMBASE and the Cochrane database. Three observational studies met our
      inclusion criteria and were included in the data analysis. The pooled risk ratio
      of venous thromboembolism in patients with IIM compared with non-IIM participants
      was 2.85 (95 % CI 2.12-3.84). Our result indicates a significant increased risk
      of venous thromboembolism among patients with IIM. 

PMID- 24748493
TI  - The relative proportions of different lipid classes and their fatty acid
      compositions change with culture age in the cariogenic dental pathogen
      Streptococcus mutans UA159.
AB  - The oral cariogenic bacterial pathogen Streptococcus mutans strain UA159 has
      become an important research organism strain since its genome was sequenced.
      However, there is a paucity of information on its lipidome using direct
      analytical biochemical approaches. We here report on comprehensive analyses of
      the major lipid classes and their fatty acids in cells grown in batch standing
      cultures. Using 2-D high-performance thin-layer chromatography lipid class
      composition changes were detected with culture age. More lipid components were
      detected in the stationary-phase compared to log-phase cells. The major lipids
      identified included 1,3-bis(sn-3'-phosphatidyl)-sn-glycerol
      (phosphatidylglycerol), 1,3-diphosphatidylglycerol (cardiolipin), aminoacyl
      phosphatidylglycerol, monoglucosyldiacylglycerol, diglucosyldiacylglycerol,
      diglucosylmonoacylglycerol and, glycerophosphoryldiglucosyldiacylglycerol.
      Culture age also affected the fatty acid composition of the total polar lipid
      fraction. Thus, the major lipid classes detected in log-phase and stationary
      phase cells were isolated and their fatty acids were analyzed by gas-liquid
      chromatography to determine the basis for the fatty acid compositional changes in
      the total polar lipid fraction. The analyses showed that the relative proportions
      of these acids changed with culture age within individual lipid classes. Hence
      fatty acid changes in the total polar lipid fraction reflected changes in both
      lipid class composition and fatty acid compositions within individual lipid
      classes. 

PMID- 24748494
TI  - CD8 T cells use IFN-gamma to protect against the lethal effects of a respiratory
      poxvirus infection.
AB  - CD8 T cells are a key component of immunity to many viral infections. They
      achieve this through using an array of effector mechanisms, but precisely which
      component/s are required for protection against a respiratory orthopox virus
      infection remains unclear. Using a model of respiratory vaccinia virus infection
      in mice, we could specifically determine the relative contribution of perforin,
      TRAIL, and IFN-gamma-mediated pathways in protection against virus induced
      morbidity and mortality. Unexpectedly, we observed that protection against death
      was mediated by IFN-gamma without any involvement of the perforin or TRAIL
      dependent pathways. IFN-gamma mRNA and protein levels in the lung peaked between
      days 3 and 6 postinfection. This enhanced response coincided with the emergence
      of virus-specific CD8 T cells in the lung and the cessation of weight loss.
      Transfer experiments indicated that CD8 T cell-autonomous expression of IFN-gamma
      restricts virus-induced lung pathology and dissemination to visceral tissues and
      is necessary for clearance of virus. Most significantly, we show that CD8 T cell
      derived IFN-gamma is sufficient to protect mice in the absence of CD4 and B
      lymphocytes. Thus, our findings reveal a previously unappreciated mechanism by
      which effector CD8 T cells afford protection against a highly virulent
      respiratory orthopox virus infection. 

PMID- 24748495
TI  - B cells are not essential for Lactobacillus-mediated protection against lethal
      pneumovirus infection.
AB  - We have shown previously that priming of respiratory mucosa with live
      Lactobacillus species promotes robust and prolonged survival from an otherwise
      lethal infection with pneumonia virus of mice, a property known as heterologous
      immunity. Lactobacillus priming results in a moderate reduction in virus recovery
      and a dramatic reduction in virus-induced proinflammatory cytokine production;
      the precise mechanisms underlying these findings remain to be elucidated. Because
      B cells have been shown to promote heterologous immunity against respiratory
      virus pathogens under similar conditions, in this study we explore the role of B
      cells in Lactobacillus-mediated protection against acute pneumovirus infection.
      We found that Lactobacillus-primed mice feature elevated levels of airway Igs
      IgG, IgA, and IgM and lung tissues with dense, B cell (B220(+))-enriched
      peribronchial and perivascular infiltrates with germinal centers consistent with
      descriptions of BALT. No B cells were detected in lung tissue of Lactobacillus
      primed B cell deficient MUMT mice or Jh mice, and Lactobacillus-primed MUMT mice
      had no characteristic infiltrates or airway Igs. Nonetheless, we observed
      diminished virus recovery and profound suppression of virus-induced
      proinflammatory cytokines CCL2, IFN-gamma, and CXCL10 in both wild-type and
      Lactobacillus-primed MUMT mice. Furthermore, Lactobacillus plantarum-primed, B
      cell-deficient MUMT and Jh mice were fully protected from an otherwise lethal
      pneumonia virus of mice infection, as were their respective wild-types. We
      conclude that B cells are dispensable for Lactobacillus-mediated heterologous
      immunity and were not crucial for promoting survival in response to an otherwise
      lethal pneumovirus infection. 

PMID- 24748496
TI  - Donor killer cell Ig-like receptor B haplotypes, recipient HLA-C1, and HLA-C
      mismatch enhance the clinical benefit of unrelated transplantation for acute
      myelogenous leukemia.
AB  - Killer cell Ig-like receptors (KIRs) interact with HLA class I ligands to
      regulate NK cell development and function. These interactions affect the outcome
      of unrelated donor hematopoietic cell transplantation (HCT). We have shown
      previously that donors with KIR B versus KIR A haplotypes improve the clinical
      outcome for patients with acute myelogenous leukemia by reducing the incidence of
      leukemic relapse and improving leukemia-free survival (LFS). Both centromeric and
      telomeric KIR B genes contribute to the effect, but the centromeric genes are
      dominant. They include the genes encoding inhibitory KIRs that are specific for
      the C1 and C2 epitopes of HLA-C. We used an expanded cohort of 1532 T cell
      replete transplants to examine the interaction between donor KIR B genes and
      recipient class I HLA KIR ligands. The relapse protection associated with donor
      KIR B is enhanced in recipients who have one or two C1-bearing HLA-C allotypes,
      compared with C2 homozygous recipients, with no effect due to donor HLA. The
      protective interaction between donors with two or more, versus none or one, KIR B
      motifs and recipient C1 was specific to transplants with class I mismatch at HLA
      C (RR of leukemia-free survival, 0.57 [0.40-0.79]; p = 0.001) irrespective of the
      KIR ligand mismatch status of the transplant. The survival advantage and relapse
      protection in C1/x recipients compared with C2/C2 recipients was similar
      irrespective of the particular donor KIR B genes. Understanding the interactions
      between donor KIR and recipient HLA class I can be used to inform donor selection
      to improve outcome of unrelated donor hematopoietic cell transplantation for
      acute myelogenous leukemia. 

PMID- 24748497
TI  - M-CSF inhibits anti-HIV-1 activity of IL-32, but they enhance M2-like phenotypes
      of macrophages.
AB  - M-CSF promotes the differentiation and survival of macrophages, and
      preferentially induces anti-inflammatory M2, rather than proinflammatory M1
      macrophages. Recently, another cytokine, IL-32, was also shown to promote
      macrophage differentiation. In this article, we provide the first evidence, to
      our knowledge, that M-CSF has both additive and inhibitory effects on the
      macrophage-related activities of IL-32. When added to M-CSF-derived macrophages,
      M-CSF and IL-32 promoted macrophage survival, which was further enhanced by their
      combination. However, they had different effects on HIV-1 replication; that is,
      it was stimulated by M-CSF and inhibited by IL-32. Interestingly, the anti-HIV-1
      activity of IL-32 was counteracted by M-CSF. Such inhibitory effect of M-CSF was
      not observed with IL-32-induced M1-like features including high
      cytokine/chemokine production and strong expression of the costimulatory molecule
      CD80. However, IL-32-treated macrophages unexpectedly showed also M2-like
      features including increased phagocytic activity, and high expression of CD14 and
      the scavenger receptor CD163, and the expression of CD14 and CD163 was further
      upregulated by cotreatment with M-CSF. The findings of this study regarding the
      unique functional interplay between M-CSF and IL-32 increase our understanding of
      the mechanisms that regulate the survival and M1/M2 ratio of macrophages, as well
      as HIV-1 replication in macrophages. 

PMID- 24748498
TI  - Regional bias of intratumoral genetic heterogeneity of nucleotide repeats in
      colon cancers with microsatellite instability.
AB  - Intratumoral heterogeneity (ITH) may produce regional biases in genotype and
      phenotype evaluation in a single tumor and may impede proper cancer diagnosis. To
      evaluate the extent of ITH in colorectal cancer (CRC) with microsatellite
      instability (MSI), we obtained 4-7 biopsies from 39 CRCs followed by MSI analysis
      either using the Bethesda MSI evaluation system or Promega system with 5
      mononucleotide markers. We found decreased prevalence of MSI (+) by the Promega
      system compared to the Bethesda system. The overall discordance between the two
      systems was 54 %. In contrast to the previous studies that had shown discordance
      only in low MSI (MSI-L), our results showed the discordance not only in MSI-L,
      but also in high MSI (MSI-H) cases. Among the MSI (+) CRCs, ITH of MSI status was
      identified in 41.7 % of CRC by the Bethesda system and 22.2 % by the Promega
      system. In terms of MSI markers, the ITH originated from dinucleotide markers in
      most cases (69 %), but it originated from mononucleotide markers (31 %) as well.
      Pooling of DNA from a regional biopsy with MSI (+) with additional biopsies from
      stable MSI (MSS) showed that this approach was beneficial to increase the
      sensitivity of MSI detection. Our results indicate that ITH of MSI phenotype by
      the Bethesda system is more overestimated than previously identified. However,
      because there was considerable ITH of MSI subtypes and markers even by the
      Promega system, our data suggest that analysis of MSI status in multiple regional
      biopsies is needed for a better evaluation of MSI status in CRC.

PMID- 24748499
TI  - Risking it for love: romantic relationships and early pubertal development confer
      risk for later disruptive behavior disorders in African-American girls receiving
      psychiatric care.
AB  - Disruptive behavior problems (DBP) represent a growing concern for young women
      (e.g., Snyder and Sickmund, 2006), but gender-specific investigations have been
      traditionally underrepresented in this area. The purpose of this study is to
      examine the associations among gender-relevant risk factors for DBP among 217
      African American girls in psychiatric care. African American girls, 12-16 years
      old (M = 14.6; SD = 1.2), and their primary female caregivers (N = 254) were
      recruited from outpatient mental health clinics and reported on girls' DBP,
      heterosexual dating experiences (romantic and sexual), peer relationships,
      pubertal development, and self-silencing at baseline, 6-, and 12 months.
      Structural Equation Modeling examined evidence for full versus mediated (via self
      silencing) models and the structural relationships (direct and indirect) among
      key study variables. Results suggest that the full model was a significantly
      better fit than the mediated model as indicated by a Chi-squared difference test
      (p < 0.01). In the full model, direct effects of greater romantic dating
      experiences and lower quality peer relationships at baseline predicted DBP at 12
      months. Sexual dating experiences were more strongly linked with DBP at 12 months
      for early maturing compared to average or later maturing girls. Indirect effects
      analyses suggested that girls' suppression of relational needs, assessed through
      a measure of self-silencing, explained the association between peer relationships
      and DBP. Findings highlight the importance of the relational context for girls'
      DBP, with treatment implications supporting relationship-based models of care,
      early intervention, and skill building around negotiating needs with peers and
      partners. 

PMID- 24748500
TI  - Increased incidence of osteoarthritis of knee joint after ACL reconstruction with
      bone-patellar tendon-bone autografts than hamstring autografts: a meta-analysis
      of 1,443 patients at a minimum of 5 years.
AB  - PURPOSE: The objective of this study was to evaluate the effectiveness of BPTB
      autografts versus HT autografts at a minimum of 5 years after anterior cruciate
      ligament (ACL) reconstruction. METHODS: A systematical search of literature was
      performed in PubMed, Embase and the Cochrane library to identify published
      randomized controlled trials (RCT) or prospective cohort studies (PCS) relevant
      to ACL reconstruction comparing BPTB and HT autografts. The results of the
      eligible studies were analysed in terms of objective International Knee
      Documentation Committee (IKDC) scores, return to preinjury activity level, KT
      1000, Lachman test, pivot shift test, anterior knee pain, kneeling pain,
      extension loss, and flexion loss, graft failure and radiographic outcomes. Study
      quality was assessed by using the Coleman methodology score for included studies.
      Two reviewers independently assessed each study for quality and extracted data.
      Subgroup analysis of the primary outcomes was conducted according to the type of
      study design (RCT or PCS). RESULTS: Twelve RCTs, two PCS including 1,443 patients
      comparing hamstring and patellar tendon autografts were identified. The results
      of the meta-analysis showed that there were no significant differences between
      BPTB and HT in terms of objective IKDC score (P = 0.83), return to preinjury
      activity (P = 0.69), KT-1000 (P = 0.12), Lachman test (P = 0.76), pivot shift
      test (P = 0.11), extension deficit (P = 0.09), flexion deficit (P = 0.71) and
      graft failure (P = 0.22). However, outcomes in favour of HT autografts were found
      in terms of anterior knee pain (P = 0.0001) and kneeling pain (P = 0.001).
      Radiographic evidence of osteoarthritis (OA) showed that incidence of OA was
      significantly higher in BPTB groups compared with HT groups based on IKDC system.
      These findings were still robust during the sensitivity analysis. Results from
      subgroup analysis of the primary outcomes were consistent with the overall
      analysis. CONCLUSION: Meta-analysis of prospective trials did not detect any
      significant differences in clinical results, as evidenced by the objective IKDC
      score, return to preinjury activity level, KT-1000, Lachman test, pivot shift
      test, extension loss, flexion loss and graft failure. However, the meta-analysis
      revealed that ACL reconstruction with BPTB autografts resulted in increased
      anterior knee pain and kneeling pain compared with hamstring autografts.
      Increased incidence of OA was found after ACL reconstruction at a minimum of 5
      years in BPTB group compared with HT autografts. This result should be cautiously
      interpreted. More high-quality RCT with strictly specified inclusion criteria are
      highly required before drawing a reliable conclusion.

PMID- 24748501
TI  - Predictive value of CHFR and MLH1 methylation in human gastric cancer.
AB  - BACKGROUND: Gastric carcinoma (GC) has one of the highest mortality rates of
      cancer diseases and has a high incidence rate in China. Palliative chemotherapy
      is the main treatment for advanced gastric cancer. It is necessary to compare the
      effectiveness and toxicities of different regimens. This study explores the
      possibility of methylation of DNA damage repair genes serving as a prognostic and
      chemo-sensitive marker in human gastric cancer. METHODS: The methylation status
      of five DNA damage repair genes (CHFR, FANCF, MGMT, MLH1, and RASSF1A) was
      detected by nested methylation-specific PCR in 102 paraffin-embedded gastric
      cancer samples. Chi-square or Fisher's exact tests were used to evaluate the
      association of methylation status and clinic-pathological factors. The Kaplan
      Meier method and Cox proportional hazards models were employed to analyze the
      association of methylation status and chemo-sensitivity. RESULTS: The results
      indicate that CHFR, MLH1, RASSF1A, MGMT, and FANCF were methylated in 34.3%
      (35/102), 21.6% (22/102), 12.7% (13/102), 9.8% (10/102), and 0% (0/102) of
      samples, respectively. No association was found between methylation of CHFR,
      MLH1, RASSF1A, MGMT, or FANCF with gender, age, tumor size, tumor
      differentiation, lymph node metastasis, and TNM stage. In docetaxel-treated
      gastric cancer patients, resistance to docetaxel was found in CHFR unmethylated
      patients by Cox proportional hazards model (HR 0.243, 95% CI, 0.069-0.859, p =
      0.028), and overall survival is longer in the CHFR methylated group compared with
      the CHFR unmethylated group (log-rank, p = 0.036). In oxaliplatin-treated gastric
      cancer patients, resistance to oxaliplatin was found in MLH1 methylated patients
      (HR 2.988, 95% CI, 1.064-8.394, p = 0.038), and overall survival was longer in
      the MLH1 unmethylated group compared with the MLH1 methylated group (log-rank, p
      = 0.046). CONCLUSIONS: CHFR is frequently methylated in human gastric cancer, and
      CHFR methylation may serve as a docetaxel-sensitive marker. MLH1 methylation was
      related to oxaliplatin resistance in gastric cancer patients.

PMID- 24748502
TI  - Progress in quantitative single-molecule localization microscopy.
AB  - With the advent of single-molecule localization microscopy (SMLM) techniques,
      intracellular proteins can be imaged at unprecedented resolution with high
      specificity and contrast. These techniques can lead to a better understanding of
      cell functioning, as they allow, among other applications, counting the number of
      molecules of a protein specie in a single cell, studying the heterogeneity in
      protein spatial organization, and probing the spatial interactions between
      different protein species. However, the use of these techniques for accurate
      quantitative measurements requires corrections for multiple inherent sources of
      error, including: overcounting due to multiple localizations of a single
      fluorophore (i.e., photoblinking), undercounting caused by incomplete
      photoconversion, uncertainty in the localization of single molecules, sample
      drift during the long imaging time, and inaccurate image registration in the case
      of dual-color imaging. In this paper, we review recent efforts that address some
      of these sources of error in quantitative SMLM and give examples in the context
      of photoactivated localization microscopy (PALM).

PMID- 24748503
TI  - Sensory innervation of the dorsal longitudinal ligament and the meninges in the
      lumbar spine of the dog.
AB  - Although intervertebral disc herniation is a well-known disease in dogs, pain
      management for this condition has remained a challenge. The goal of the present
      study is to address the lack of information regarding the innervation of
      anatomical structures within the canine vertebral canal. Immunolabeling was
      performed with antibodies against protein gene product 9.5, Tuj-1 (neuron
      specific class III beta-tubulin), calcitonin gene-related peptide, and
      neuropeptide Y in combination with the lectin from Lycopersicon esculentum as a
      marker for blood vessels. Staining was indicative of both sensory and sympathetic
      fibers. Innervation density was the highest in lateral areas, intermediate in
      dorsal areas, and the lowest in ventral areas. In the dorsal longitudinal
      ligament (DLL), the highest innervation density was observed in the lateral
      regions. Innervation was lower at mid-vertebral levels than at intervertebral
      levels. The presence of sensory and sympathetic fibers in the canine dura and DLL
      suggests that pain may originate from both these structures. Due to these
      regional differences in sensory innervation patterns, trauma to intervertebral
      DLL and lateral dura is expected to be particularly painful. The results ought to
      provide a better basis for the assessment of medicinal and surgical procedures. 

PMID- 24748504
TI  - Phosphatase and actin regulator 4 is associated with intermediate filaments in
      adult neural stem cells and their progenitor astrocytes.
AB  - Phosphatase and actin regulator 4 (Phactr4) is a newly discovered protein that
      inhibits protein phosphatase 1 and shows actin-binding activity. We previously
      found that Phactr4 is expressed in the neurogenic niche in adult mice, although
      its precise subcellular localization and possible function in neural stem cells
      (NSCs) is not yet understood. Here, we show that Phactr4 formed punctiform
      clusters in the cytosol of subventricular zone-derived adult NSCs and their
      progeny in vitro. These Phactr4 signals were not associated with F-actin fibers
      but were closely associated with intermediate filaments such as nestin and glial
      fibrillary acidic protein (GFAP) fibers. Direct binding of Phactr4 with nestin
      and GFAP filaments was demonstrated using Duolink protein interaction analyses
      and immunoprecipitation assays. Interestingly, when nestin fibers were de
      polymerized during the mitosis or by the phosphatase inhibitor, Phactr4 appeared
      to be dissociated from nestin, suggesting that their protein interaction is
      regulated by the protein phosphorylation. These results suggest that Phactr4
      forms functional associations with intermediate filament networks in adult NSCs. 

PMID- 24748505
TI  - Increased serum APRIL differentially correlates with distinct cytokine profiles
      and disease activity in systemic lupus erythematosus patients.
AB  - Cytokines play an important role in the pathogenesis of systemic lupus
      erythematosus (SLE). Among the cytokines that regulate B cell homeostasis is a
      proliferation-inducing ligand (APRIL). This study aimed to determine whether
      serum levels of APRIL are raised in patients with SLE and correlate with disease
      activity or proinflammatory cytokines production, or both. Serum APRIL,
      interleukin-17 (IL-17), IL-4 and interferon gamma (IFN-gamma) levels were
      measured in forty patients with SLE and 30 healthy controls. Disease activity was
      assessed by SLE disease activity index (SLEDAI), and results were correlated with
      serum APRIL levels. Serum APRIL levels were significantly higher in patients with
      SLE than in healthy controls. Positive correlation was found between serum APRIL
      levels and total SLEDAI score and anti-dsDNA antibody titers. Moreover, serum
      APRIL levels was significantly higher in patients with arthritis, mucocutaneous
      manifestations and proteinuria. APRIL is increased in patients with active SLE
      accompanying the increase of IL-17 and IFN-gamma. Significant positive
      correlations between serum levels of APRIL and IL-17 and IFN-gamma and a negative
      correlation between serum levels of APRIL and IL-4 were found. The results
      suggest that APRIL may be an important marker of disease activity in patients
      with SLE. We provide the analyses of APRIL levels in patients with SLE,
      suggesting new tools for the diagnosis, prognosis and possible therapeutic
      management of SLE. 

PMID- 24748506
TI  - Pharmaceutical care: the PCNE definition 2013.
AB  - BACKGROUND: Twenty-three years after Hepler and Strand published their well-known
      definition of Pharmaceutical Care (PhC), confusion remains about what the term
      includes and how to differentiate it from other terms. The board of the
      Pharmaceutical Care Network Europe (PCNE) felt the need to redefine PhC and to
      answer the question: "What is Pharmaceutical Care in 2013". OBJECTIVE: The aims
      of this paper were to review existing definitions of PhC and to describe the
      process of developing a redefined definition. METHODS: A literature search was
      conducted in the MEDLINE database (1964-January 2013). Keywords included
      "Pharmaceutical Care", "Medication (Therapy) Management", "Medicine Management",
      and "Pharmacist Care" in the title or abstract together with the term "defin*".
      To ease comparison between definitions, we developed a standardised syntax to
      paraphrase the definitions. During a dedicated meeting, a moderated discussion
      about the definition of PhC was organised. RESULTS: The initial literature search
      produced 186 hits, with eight unique PhC definitions. Hand searching identified a
      further 11 unique definitions. These 19 definitions were paraphrased using the
      standardised syntax (provider, recipient, subject, outcome, activities). Fourteen
      members of PCNE and 10 additional experts attended the moderated discussion.
      Working groups of increasing size developed intermediate definitions, which had
      similarities and differences to those retrieved in the literature search. At the
      end of the session, participants reached a consensus on a "PCNE definition of
      Pharmaceutical Care" reading: "Pharmaceutical Care is the pharmacist's
      contribution to the care of individuals in order to optimize medicines use and
      improve health outcomes". CONCLUSIONS: It was possible to paraphrase definitions
      of PhC using a standardised syntax focusing on the provider, recipient, subject,
      outcomes, and activities included in PhC practice. During a one-day workshop,
      experts in PhC research agreed on a definition, intended to be applicable for the
      present time, representative for various work settings, and valid for countries
      inside and outside of Europe.

PMID- 24748507
TI  - Evidence based development of bedside clinical drug rules for surgical patients.
AB  - BACKGROUND: Surgical adverse events constitute a considerable problem. More than
      half of in-hospital adverse events are related to a surgical procedure.
      Medication related events are frequent and partly preventable. Due to the
      complexity and multidisciplinary nature of the surgical process, patients are at
      risk for drug related problems. Consistent drug management throughout the process
      is needed. OBJECTIVE: The aim of this study was to develop an evidence-based
      bedside tool for drug management decisions during the pre- and postoperative
      phase of the surgical pathway. SETTING: Tool development study performed in an
      academic medical centre in the Netherlands involving an expert panel consisting
      of a surgeon, a clinical pharmacist and a pharmacologist, all experienced in
      quality improvement. METHOD: Relevant medication related problems and critical
      pharmacotherapeutic decision steps in the surgical process were identified and
      prioritised by a team of experts. The final selection comprised undesirable
      effects or unintended outcomes related to surgery (e.g. pain, infection) and
      comorbidity related hazards (e.g. diabetes, cardiovascular diseases). To guide
      patient management, a list of bedside surgical drug rules was developed using
      international evidence-based guidelines. MAIN OUTCOME MEASURE: 55 bedside drug
      rules on 6 drug categories, specifically important for surgical practice, were
      developed: pain, respiration, infection, diabetes, cardiovascular diseases and
      anticoagulation. RESULTS: A total of 29 evidence-based guidelines were used to
      develop the Bedside Surgical Drug Rules tool. This tool consist of practical
      tables covering management regarding (1) the most commonly used drug categories
      during surgery, (2) comorbidities that require dosing adjustments and, (3) contra
      indicated drugs in the perioperative period. CONCLUSION: An evidence-based
      approach provides a practical basis for the development of a bedside tool to
      alert and assist the care providers in their drug management decisions along the
      surgical pathway.

PMID- 24748508
TI  - Outcome evaluation of an intervention to improve the effective and safe use of
      meropenem.
AB  - BACKGROUND: Pharmacists have been involved in promoting the proper and safe use
      of antimicrobial drugs in our institution since 2010. Setting Kochi Medical
      School Hospital, Japan. OBJECTIVE: To design and evaluate a plan of
      administration of meropenem (MEPM) based on its pharmacokinetics and
      pharmacodynamics, drug sensitivity, bacterial cultures, patient condition and
      renal function. METHOD: A total of 547 patients admitted between April 2010 and
      March 2013 with serious infections who were successfully treated with MEPM for
      three or more days were analysed. Patients were initially divided into two groups
      according to renal function: group A consisted of patients with mild renal
      dysfunction [creatinine clearance (CLcr) > 50 mL/min] while group B consisted of
      patients with moderate to severe renal dysfunction (CLcr <= 50 mL/min). These
      groups were then subdivided into two groups according to the implementation of
      pharmacist intervention. MAIN OUTCOME MEASURES: Daily dose, frequency of
      administration, dose interval, duration of therapy, adverse events and cost
      reduction. RESULTS: In the non-intervention subgroup within group A, the daily
      dose was 1,000 mg/day, the frequency of administration was 1.8 +/- 0.6 times/day,
      and the duration of therapy was 9.4 +/- 5.4 days. In the intervention subgroup
      within group A, the daily dose was 1,500 mg/day, the administration frequency was
      2.5 +/- 0.6 times/day, and the duration of therapy was 7.4 +/- 3.7 days. Although
      the dose was higher (P < 0.05) and the duration of therapy was an average of 2
      days shorter (P < 0.05) in the intervention subgroup, there was no significant
      difference in the rate of adverse events between the two subgroups. In group B,
      there were no significant differences between the two subgroups in the daily
      dose, administration frequency, or duration of therapy. However, liver
      dysfunction was significantly more common in the non-intervention subgroup than
      in the intervention subgroup (P < 0.05). The total reduction in drug cost in the
      intervention groups was estimated to be US$17,490 over 3 years. CONCLUSION:
      Pharmacist intervention was associated with a shorter duration of therapy, lower
      drug costs, and decreased adverse effect. We believe that our intervention is
      beneficial in terms of effectiveness and safety, and supports proper
      antimicrobial use.

PMID- 24748509
TI  - Rumen metabolism of 22:6n-3 in vitro is dependent on its concentration and
      inoculum size, but less dependent on substrate carbohydrate composition.
AB  - Ruminal disappearance of linoleic and linolenic acid has been studied
      extensively. Less is known of the metabolism of docosahexaenoic acid (22:6n-3).
      The aim of this study was to identify factors which affect the disappearance of
      22:6n-3 during in vitro batch incubations using rumen fluid from sheep. In
      experiment 1, the effect of the rumen fluid/buffer ratio (0.2 or 0.4), substrate
      (cellulose or cellulose/glucose), time of 22:6n-3 addition (0.08 mg/mL after 0 or
      6 h of incubation) and incubation time (24 or 48 h) was evaluated. A mixture
      design was used in experiment 2 to evaluate the effect of carbohydrate type
      (cellulose, glucose, cellobiose and starch) on 22:6n-3 disappearance (0.08
      mg/mL). In experiment 3, several concentrations of 22:6n-3 (0.05-0.30 mg/mL) were
      evaluated with different substrate mixtures (combinations of cellobiose, starch
      and cellulose). In a final experiment, the effect of the rumen fluid/buffer ratio
      (0.20, 0.35 and 0.50) and substrate (glucose, cellobiose and starch) was
      evaluated. In this experiment, 22:6n-3 was added as a proportion of rumen fluid
      ranging from 0.1 to 0.4 mg/mL rumen fluid, contrary to former experiments where
      concentrations were relative to culture medium. Low levels of 22:6n-3 (0.05
      mg/mL) allowed extensive metabolism whereas increasing amounts of 22:6n-3
      hampered its disappearance. A greater proportion of rumen fluid resulted in
      increased disappearance of 22:6n-3. The effect of carbohydrate type was small
      compared with the former two factors. These results suggest that in vitro
      metabolism of 22:6n-3 is mostly dictated by the conditions at the start of the
      incubation, i.e., inoculum, probably reflecting the density of bacteria able to
      metabolize 22:6n-3.

PMID- 24748510
TI  - Effect of optogenetic stimulus on the proliferation and cell cycle progression of
      neural stem cells.
AB  - Modulation of stem cell proliferation is a crucial aspect of neural developmental
      biology and regenerative medicine. To investigate the effect of optical
      stimulation on neural stem cell proliferation, cells transduced with
      channelrhodopsin-2 (ChR2) were used to analyze changes in cell proliferation and
      cell cycle distribution after light stimulation. Blue light significantly
      inhibited cell proliferation and affected the cell cycle, which increased the
      percentage of cells in G1 phase and reduced the percentage in S phase. It is
      likely that the influence of blue light on cell proliferation and the cell cycle
      was mediated by membrane depolarization, which induced accumulation of p21 and
      p27 proteins. Our data provide additional specific evidence that membrane
      depolarization may inhibit neural stem cell proliferation. 

PMID- 24748511
TI  - Tissue distribution and excretion of herbal components after intravenous
      administration of a Chinese medicine (Shengmai injection) in rat.
AB  - Shengmai injection, consisting of Panax ginseng, Radix ophiopogonis and
      Schisandra chinensis, is a widely used Chinese medicine for the treatment of
      various cardiovascular diseases. In this study, tissue distribution and excretion
      of its multiple active components including protopanaxatriol-type (Ppt-type)
      ginsenosides (ginsenoside Rg1, Re, Rf and Rg2), protopanaxadiol-type (Ppd-type)
      ginsenosides (ginsenoside Rb1, Rd and Rc), ophiopogonin (ophiopogonin D), and
      lignan (schisandrin, schisandrol B and schizandrin B) in rat after single
      intravenous administration of Shengmai injection were reported. Ppt-type
      ginsenosides exhibited quick and wide distribution from blood into tissues and
      were eliminated rapidly through biliary, urinary and fecal excretions. Ppd-type
      ginsenosides Rb1, Rd and Rc distributed quickly from blood to all tissues but
      exhibited slow elimination by biliary and urinary excretions. Ophiopogonin D was
      excreted into bile with no urinary and fecal excretion, indicating its
      elimination in the form of secondary metabolites. Schisandrin, schisandrol B and
      schizandrin B was found to distribute quickly from blood into most tissues and
      had accumulation in these tissues. Very low biliary, urinary and fecal excretion
      implied that lignan was mainly excreted in the form of their metabolites. This
      study produced a first hand in vivo tissue distribution and dynamic profiles of
      the active components of Shengmai injection, providing valuable information for
      drug development and clinical application of Shengmai injection.

PMID- 24748512
TI  - Resiquimod, a TLR7/8 agonist, promotes differentiation of myeloid-derived
      suppressor cells into macrophages and dendritic cells.
AB  - Myeloid-derived suppressor cells (MDSCs) accumulate in cancer patients and tumor
      bearing mice, subsequently suppressing the host immune system. MDSCs represent a
      group of immature myeloid cells expressing CD11b and Gr-1. Here, we show that a
      Toll-like receptor (TLR) agonist, resiquimod, which binds to TLR7 and TLR8,
      induces the differentiation of MDSCs into mature myeloid cells. MDSCs were
      isolated from mice bearing mammary carcinoma 4T1 cells, and the purified MDSCs
      were cultured in the presence of resiquimod for 5 days. Phenotypic analysis
      showed that the resiquimod-treated MDSCs differentiated into F4/80+ macrophages
      and CD11c+/I-A(d+) dendritic cells. Functional analysis showed that the MDSCs
      also lost their suppressive activity on T cells. Resiquimod-treated MDSCs
      significantly enhanced the proliferation of T cells that were treated with anti
      CD3 and anti-CD28 monoclonal antibodies. These results show that resiquimod
      induces the differentiation of MDSCs into macrophages and dendritic cells, and
      also suggest that resiquimod may improve cancer immunotherapy by reducing
      immunosuppressive MDSCs.

PMID- 24748513
TI  - Lignan and flavonoids from the stems of Zea mays and their anti-inflammatory and
      neuroprotective activities.
AB  - The stems of Zea mays L., otherwise known as cornstalks, were extracted with 80 %
      aqueous MeOH, and the concentrated extract was successively partitioned with
      ethyl acetate (EtOAc), normal butanol, and water. From the EtOAc fraction, a new
      lignan along with three known flavonoids, tricin (1), salcolin A (2), and
      salcolin B (3), were isolated. The chemical structure of the lignan was
      determined to be tetrahydro-4,6-bis(4-hydroxy-3-methoxyphenyl)-1H,3H-furo[3,4
      c]furan-1-one (4) through spectroscopic data analyses including NMR, MS, and IR.
      All compounds were isolated for the first time from this plant. The isolated
      compounds were evaluated for their inhibitory activity against NO production in
      Lipopolysaccharide-induced RAW 264.7 cells and their protective activity in
      glutamate-induced cell death in HT22 cells. The compounds 1, 2 and 4 showed anti
      inflammatory effects with IC50 values of 2.63, 14.65, and 18.91 MUM,
      respectively, as well as neuroprotective effects with EC50 values of 25.14,
      47.44, and >80 MUM, respectively.

PMID- 24748514
TI  - Potential antimalarial derivatives from astraodorol.
AB  - Astraodorol, a major lanostane-type triterpene isolated from the edible mushroom
      Astraeus odoratus, was subjected to chemical modifications. Ten derivatives have
      been synthesized and their biological activities were evaluated. Compounds 5, 6,
      7a, 7c, 7e, 7f, and 7 g exhibited strong antimalarial activity with IC50 values
      of 4.85, 4.48, 4.16, 4.46, 3.45, 3.23, and 3.41 ug/mL, respectively. Compounds
      7a, 7c, and 7e showed moderate cytotoxicity against NCI-H187 with IC50 values of
      23.36, 34.28, and 9.84 ug/mL. Compound 7e demonstrated moderate cytotoxicity
      against KB, MCF-7, and Vero cell lines with IC50 values of 16.94, 49.60, and
      26.48 ug/mL, respectively.

PMID- 24748515
TI  - Carotid endarterectomy using a "home-constructed" shunt for patients intolerant
      to cross-clamping.
AB  - PURPOSES: There is a small minority of patients with occlusive carotid artery
      disease, who are at high-risk for general anesthesia because of their intolerance
      to carotid flow blockage, even if only for seconds, without neurologic deficit.
      Even <30 s of temporary clamping of the carotid arteries to deploy a shunt may
      prove eventful in this patient group. We define safe carotid endarterectomy after
      the insertion of a novel shunt that we made from simple medical equipment in this
      patient population. METHODS: Among 65 patients who underwent carotid
      endarterectomy between March 2010 and December 2012, 5 (7.7 %; 3 men and 2 women;
      age range 56-77 years) could not tolerate carotid clamping. We used an
      alternative carotid shunt, made by us from simple equipment in our clinic, during
      surgery for these patients. RESULTS: Two patients had bilateral lesions and the
      remainder had unilateral disease. The degree of stenosis ranged from 70 to 95 %.
      Temporary carotid clamping resulted in neurologic events, such as loss of
      consciousness in all and tremor in one, in <10 s (range, from immediately to 8 s
      after clamping). Full neurologic function was regained 15-30 s after releasing
      the clamps. All of the patients tolerated the procedures well with the support of
      our novel shunt. Shunt flow was adequate in all patients and no neurologic
      deterioration occurred after carotid clamping. The mean carotid clamp time was
      28.11 +/- 14.19 min. There was no mortality and all patients were followed up for
      a mean period of 9.3 +/- 3.6 months, uneventfully. CONCLUSIONS: An alternative,
      simple shunt, which is easily constructed in the operating room or clinic, using
      an angiocatheter, a three-way stopcock, and a serum line can provide adequate
      cerebral flow and permit safe carotid endarterectomy for those rare patients with
      carotid artery stenosis, who cannot tolerate even seconds of carotid occlusion.

PMID- 24748516
TI  - Investigating the effect of SiO2-TiO 2-CaO-Na 2O-ZnO bioactive glass doped
      hydroxyapatite: characterisation and structural evaluation.
AB  - The effects of increasing bioactive glass additions, SiO2-TiO2-CaO-Na2O-ZnO up to
      25 wt% in increments of 5 wt%, on the physical and mechanical properties of
      hydroxyapatite (HA) sintered at 900, 1000, 1100 and 1200  degrees C for 2 h was
      investigated. Increasing both the glass content and the temperature resulted in
      increased HA decomposition. This resulted in the formation of a number of
      bioactive phases. However the presence of the liquidus glass phase did not result
      in increased densification levels. At 1000 and 1100  degrees C the additions of 5
      wt% glass resulted in a decrease in density which never recovered with increasing
      glass content. At 1200  degrees C a cyclic pattern resulted from increasing glass
      content. There was no direct relationship between strength and density with all
      samples experiencing no change or a decrease in strength with increasing glass
      content. Weibull statistics displayed no pattern with increasing glass content.

PMID- 24748517
TI  - Reply to Rapose.

PMID- 24748518
TI  - Bringing the "power" to Cerner's PowerChart for antimicrobial stewardship.
AB  - The electronic medical record (EMR) has huge potential for facilitating
      antimicrobial stewardship efforts by directing providers to preferred
      antimicrobials. Cerner PowerChart currently holds the number 2 position in the
      EMR market. Although PowerChart has limited "out of the box" functionalities to
      optimize stewardship efforts, there are many potential utilities that can be
      developed to assist in stewardship practice. However, to harness the stewardship
      potential of the EMR system, significant hospital information technology
      resources are needed. Herein we describe the experiences of 3 large healthcare
      systems utilizing Cerner to facilitate prior authorization of antimicrobials,
      prospective audit and feedback of antimicrobials, and supplemental stewardship
      strategies. 

PMID- 24748520
TI  - Early HIV detection: responsibility of physicians or church?

PMID- 24748519
TI  - Adenovirus species C is associated with chronic suppurative lung diseases in
      children.
AB  - BACKGROUND: The role of human adenoviruses (HAdVs) in chronic respiratory disease
      pathogenesis is recognized. However, no studies have performed molecular
      sequencing of HAdVs from the lower airways of children with chronic endobronchial
      suppuration. We thus examined the major HAdV genotypes/species, and relationships
      to bacterial coinfection, in children with protracted bacterial bronchitis (PBB)
      and mild bronchiectasis (BE). METHODS: Bronchoalveolar lavage (BAL) samples of
      245 children with PBB or mild (cylindrical) BE were included in this prospective
      cohort study. HAdVs were genotyped (when possible) in those whose BAL had HAdV
      detected (HAdV(+)). Presence of bacterial infection (defined as >=10(4) colony
      forming units/mL) was compared between BAL HAdV(+) and HAdV negative (HAdV(-))
      groups. Immune function tests were performed including blood lymphocyte subsets
      in a random subgroup. RESULTS: Species C HAdVs were identified in 23 of 24 (96%)
      HAdV(+) children; 13 (57%) were HAdV-1 and 10 (43%) were HAdV-2. An HAdV(+) BAL
      was significantly associated with bacterial coinfection with Haemophilus
      influenzae, Moraxella catarrhalis, or Streptococcus pneumoniae (odds ratio [OR],
      3.27; 95% confidence interval, 1.38-7.75; P = .007) and negatively associated
      with Staphylococcus aureus infection (P = .03). Young age was related to
      increased rates of HAdV(+). Blood CD16 and CD56 natural killer cells were
      significantly more likely to be elevated in those with HAdV (80%) compared with
      those without (56.1%) (P = .027). CONCLUSIONS: HAdV-C is the major HAdV species
      detected in the lower airways of children with PBB and BE. Younger age appears to
      be an important risk factor for HAdV(+) of the lower airways and influences the
      likelihood of bacterial coinfection.

PMID- 24748521
TI  - Comparing clinical characteristics between hospitalized adults with laboratory
      confirmed influenza A and B virus infection.
AB  - We challenge the notion that influenza B is milder than influenza A by finding
      similar clinical characteristics between hospitalized adult influenza-cases.
      Among patients treated with oseltamivir, length of stay and mortality did not
      differ by type of virus infection. 

PMID- 24748522
TI  - Reevaluation of the risk of fetal death and malformation after Q Fever.
AB  - A meta-analysis of 136 Q fever pregnancies, including 4 new cases and 7
      population-based serological studies, revealed significant increases in fetal
      death and malformation after Q fever during pregnancy. This poor obstetric
      outcome is prevented by antibiotic treatment. 

PMID- 24748523
TI  - Pertussis vaccine performance in an epidemic year-Oregon, 2012.
AB  - A 2012 pertussis epidemic in Oregon afforded an opportunity to measure vaccine
      effectiveness; it ranged from 95% (95% confidence interval [CI], 92%-97%) among
      children 15-47 months of age to 47% (95% CI, 19%-65%) among adolescents 13-16
      years of age. In all age groups, pertussis incidence was higher among unimmunized
      persons. 

PMID- 24748524
TI  - Sofosbuvir in the treatment of chronic hepatitis C: new dog, new tricks.
AB  - The existing standard of care for chronic hepatitis C virus (HCV) infection
      includes the use of pegylated interferon and ribavirin as primary components of
      treatment, with the addition of a direct-acting antiviral for genotype 1
      infection. Sofosbuvir, an oral nucleotide inhibitor of the HCV nonstructural
      protein 5B RNA-dependent RNA polymerase enzyme, was recently approved for use in
      combination with ribavirin and/or pegylated interferon for chronic HCV infection,
      depending on the genotype. Sofosbuvir is orally administered, and peak plasma
      concentrations are not affected by food. The drug is renally eliminated and does
      not require adjustment in mild to moderate renal insufficiency or in any degree
      of hepatic impairment. Sofosbuvir is not metabolized by cytochrome P450
      isoenzymes, nor does it induce or inhibit the metabolism of agents that are
      substrates of these enzymes. Sofosbuvir demonstrates a high barrier to resistance
      and was well tolerated by patients in clinical trials. Overall efficacy rates
      vary between 70% and 90%. 

PMID- 24748525
TI  - Lysine-Restricted Diet as Adjunct Therapy for Pyridoxine-Dependent Epilepsy: The
      PDE Consortium Consensus Recommendations.
AB  - BACKGROUND: Seventy-five percent of patients with pyridoxine-dependent epilepsy
      (PDE) due to Antiquitin (ATQ) deficiency suffer from developmental delay and/or
      intellectual disability (IQ < 70) despite seizure control. An observational study
      showed that adjunct treatment with a lysine-restricted diet is safe, results in
      partial normalization of lysine intermediates in body fluids, and may have
      beneficial effects on seizure control and psychomotor development. METHODS: In
      analogy to the NICE guideline process, the international PDE Consortium, an open
      platform uniting scientists and clinicians working in the field of this metabolic
      epilepsy, during four workshops (2010-2013) developed a recommendation for a
      lysine-restricted diet in PDE, with the aim of standardizing its implementation
      and monitoring of patients. Additionally, a proposal for a further observational
      study is suggested. RESULTS: (1) All patients with confirmed ATQ deficiency are
      eligible for adjunct treatment with lysine-restricted diet, unless treatment with
      pyridoxine alone has resulted in complete symptom resolution, including normal
      behavior and development. (2) Lysine restriction should be started as early as
      possible; the optimal duration remains undetermined. (3) The diet should be
      implemented and the patient be monitored according to these recommendations in
      order to assure best possible quality of care and safety. DISCUSSION: The
      implementation of this recommendation will provide a unique and a much needed
      opportunity to gather data with which to refine the recommendation as well as
      improve our understanding of outcomes of individuals affected by this rare
      disease. We therefore propose an international observational study that would
      utilize freely accessible, online data sharing technologies to generate more
      evidence.

PMID- 24748526
TI  - Diagnostic performance of CT esophagography in patients with suspected esophageal
      rupture.
AB  - Esophageal rupture is a surgical catastrophe. The gold standard for diagnosing is
      iodine, water-soluble contrast medium esophagography. CT esophagography has shown
      promising results. This study aimed to assess the diagnostic performance of CT
      esophagography in patients with a suspicion of esophageal rupture. This
      prospective study assessed the performance of a diagnostic test and was approved
      by local IRB committee. Patients who presented with a clinical suspicion of
      esophageal rupture were included. CT esophagography findings were described by
      the emergency radiologist. Clinical outcomes (presence or absence of esophageal
      rupture) were reported by surgeons. The operative characteristics were
      calculated. A final predictive scale for rupture was built. A total of 64
      patients were recruited (age 26.5 years, 90 % male, 82 % trauma). Sensitivity,
      specificity, and positive and negative likelihood ratios (LRs) were 77.7 % (95 %
      confidence interval (CI) 45-100), 94.3 % (87.2-100), 14 (9.81-19.9), and 0.24
      (0.05-1.22), respectively. The final model for predicting rupture included five
      variables: age (odds ratio (OR) 1.03; 95 % CI, 0.95-1.11; p=0.04), leakage of
      contrast media into the mediastinum or pleural space (OR 10.0; 95 % CI, 0.64
      156.9; p=0.10), extraluminal air or fluid collections (OR 43.1; 95 % CI, 1.52
      1217.3; p=0.027), esophageal wall thickening (OR 10.1; 95 % CI, 0.50-202.8;
      p=0.12), and left pneumothorax or pleural effusion (OR 6.5; 95 % CI, 0.31-132.7;
      p=0.2). The overall agreement was 0.40 (95 % CI, 0.09-0.72) for the predictive
      model. The model sensitivity was 50.0 %, and the specificity was 98.4 %. CT
      esophagography shows a good diagnostic performance in patients with a suspected
      esophageal rupture.

PMID- 24748527
TI  - A tobacco homolog of DCN1 is involved in pollen development and embryogenesis.
AB  - KEY MESSAGE: We show that DCN1 binds ubiquitin and RUB/NEDD8, associates with
      cullin, and is functionally conserved. DCN1 activity is required for pollen
      development transitions and embryogenesis, and for pollen tube growth. Plant
      proteomes show remarkable plasticity in reaction to environmental challenges and
      during developmental transitions. Some of this adaptability comes from ubiquitin
      mediated protein degradation regulated by cullin-RING E3 ubiquitin ligases
      (CRLs). CRLs are activated through modification of the cullin subunit with the
      ubiquitin-like protein RUB/NEDD8 by an E3 ligase called defective in cullin
      neddylation 1 (DCN1). Here we show that tobacco DCN1 binds ubiquitin and
      RUB/NEDD8 and associates with cullin. When knocked down by RNAi, tobacco pollen
      formation was affected and zygotic embryogenesis was blocked around the globular
      stage. Additionally, we found that RNAi of DCN1 inhibited the stress-triggered
      reprogramming of cultured microspores from their intrinsic gametophytic mode of
      development to an embryogenic state. This stress-induced developmental switch is
      a known feature in many important crops and leads ultimately to the formation of
      haploid embryos and plants. Compensating the RNAi effect by re-transformation
      with a promoter-silencing construct restored pollen development and zygotic
      embryogenesis, as well as the ability for stress-induced formation of embryogenic
      microspores. Overexpression of DCN1 accelerated pollen tube growth and increased
      the potential for microspore reprogramming. These results demonstrate that the
      biochemical function of DCN1 is conserved in plants and that its activity is
      involved in transitions during pollen development and embryogenesis, and for
      pollen tube growth.

PMID- 24748528
TI  - Long-term remission and recurrence rate in a cohort of Cushing's disease: the
      need for long-term follow-up.
AB  - OBJECTIVE: Transsphenoidal surgery is the procedure of choice in Cushing disease
      (CD), with immediate post-operative remission rates ranging between 59 and 94%
      and recurrence rates between 3 and 46%, both depending upon the definition
      criteria and the duration of the follow-up. Our aim was to assess the rate of
      remission, recurrence and persistence of the disease after the first treatment
      and to identify predictors of remission in the CD population of our center.
      METHODS: Retrospective cohort study of the patients diagnosed of CD and with
      follow-up in our center between 1974 and 2011. We analyzed 41 patients (35 women
      and 6 men) with a mean age at diagnosis of 34 +/- 13 years. The mean follow-up
      was 14 +/- 10 years (range 1-37 years) and the median of follow-up period was
      6.68 years. RESULTS: Thirty-five (85.4%) patients underwent transsphenoidal
      surgery as first treatment option. Histopathological evidence of a pituitary
      adenoma was registered in 17 (48.5%) patients. Thirty-two (78%) patients achieved
      disease remission after the first treatment, 21 (65.6%) of them presented disease
      recurrence. Persistent disease was observed in 9 (22%) patients. Twelve (29.3%)
      subjects developed post-surgical adrenal insufficiency, 7 of which (70%) achieved
      stable remission. Two parameters were found to be significant predictors of
      remission after the first treatment: age at disease diagnosis and the development
      of adrenal insufficiency (cortisol <3 MUg/dl) in the immediate post-operative
      state. CONCLUSIONS: We report a high recurrence rate, at least partially
      attributable to the long follow-up time. Early post-surgery adrenal insufficiency
      predicts remission. Hypopituitarism was also very prevalent, and strongly
      associated with radiotherapy. These results lead us to the conclusion that CD
      needs a life-long strict follow-up.

PMID- 24748529
TI  - High-intensity intermittent cycling increases purine loss compared with workload
      matched continuous moderate intensity cycling.
AB  - PURPOSE: Exercise at 50-60 % of peak oxygen consumption (VO2 peak) stimulates
      maximal fat oxidation rates. Despite a lower estimated work performed; high
      intensity intermittent exercise (HIIE) training produces greater fat mass
      reductions when compared with workload-matched continuous (CON) steady state
      exercise. No metabolic basis has been documented nor mechanisms offered to
      explain this anomaly. This study investigated the physiological and metabolic
      responses of two different workload-matched exercise protocols. METHODS: On
      separate occasions and at least 1 week apart, eight apparently healthy males
      cycled for 30 min at either 50 % VO2 peak (CON) or performed repeated 20 s bouts
      of supramaximal exercise at 150 %VO2 peak separated by 40 s rest (HIIE). RESULTS:
      The average heart rate, oxygen consumption, plasma glycerol and free fatty acid
      concentrations were not different during exercise and recovery between the
      trials. Plasma lactate and hypoxanthine (Hx) concentrations were elevated and
      urinary excretion rates of Hx and uric acid were greater following HIIE as
      compared to CON (P < 0.05). CONCLUSION: Exercise-induced plasma Hx accumulation
      and urinary purine excretion are greater following HIIE and indirectly represents
      a net loss of adenosine triphosphate (ATP) from the muscle. The subsequent
      restorative processes required for intramuscular de novo replacement of ATP may
      contribute to a negative energy balance and in part, account for the potential
      accelerated fat loss observed with HIIE when compared with CON training programs.

PMID- 24748530
TI  - Combining heat stress and moderate hypoxia reduces cycling time to exhaustion
      without modifying neuromuscular fatigue characteristics.
AB  - PURPOSE: This study investigated the isolated and combined effects of heat
      [temperate (22  degrees C/30 % rH) vs. hot (35  degrees C/40 % rH)] and hypoxia
      [sea level (FiO2 0.21) vs. moderate altitude (FiO2 0.15)] on exercise capacity
      and neuromuscular fatigue characteristics. METHODS: Eleven physically active
      subjects cycled to exhaustion at constant workload (66 % of the power output
      associated with their maximal oxygen uptake in temperate conditions) in four
      different environmental conditions [temperate/sea level (control), hot/sea level
      (hot), temperate/moderate altitude (hypoxia) and hot/moderate altitude (hot +
      hypoxia)]. Torque and electromyography (EMG) responses following electrical
      stimulation of the tibial nerve (plantar-flexion; soleus) were recorded before
      and 5 min after exercise. RESULTS: Time to exhaustion was reduced (P < 0.05) in
      hot (-35 +/- 15 %) or hypoxia (-36 +/- 14 %) compared to control (61 +/- 28 min),
      while hot + hypoxia (-51 +/- 20 %) further compromised exercise capacity (P <
      0.05). However, the effect of temperature or altitude on end-exercise core
      temperature (P = 0.089 and P = 0.070, respectively) and rating of perceived
      exertion (P > 0.05) did not reach significance. Maximal voluntary contraction
      torque, voluntary activation (twitch interpolation) and peak twitch torque
      decreased from pre- to post-exercise (-9 +/- 1, -4 +/- 1 and -6 +/- 1 % all
      trials compounded, respectively; P < 0.05), with no effect of the temperature or
      altitude. M-wave amplitude and root mean square activity were reduced (P < 0.05)
      in hot compared to temperate conditions, while normalized maximal EMG activity
      did not change. Altitude had no effect on any measured parameters. CONCLUSION:
      Moderate hypoxia in combination with heat stress reduces cycling time to
      exhaustion without modifying neuromuscular fatigue characteristics. Impaired
      oxygen delivery or increased cardiovascular strain, increasing relative exercise
      intensity, may have also contributed to earlier exercise cessation.

PMID- 24748532
TI  - Chemical constituents from the leaves of Juglans mandshurica.
AB  - Two new (1 and 3) and two known diarylheptanoids (2 and 4), along with two
      tetralones (5 and 6), one naphthoquinone (7), four phenylpropanoids (8-11), and
      one phenol (12) were isolated from the leaves of Juglans mandshurica. Their
      structures were elucidated on the basis of spectral and chemical data. Compounds
      2 and 10 are firstly isolated from this plant and 8 and 12 were isolated from the
      Juglans genus for the first time. Among these compounds, only 7 exhibited
      moderate cytotoxicities against cultured MGC-803, A549, K562, and HeLa tumor cell
      lines with IC50 values of 25.90, 28.60, 39.06, 44.90 MUM, respectively. 

PMID- 24748531
TI  - Co-ingestion of caffeine and carbohydrate after meal does not improve performance
      at high-intensity intermittent sprints with short recovery times.
AB  - PURPOSE: To determine the effects of co-ingesting caffeine (CAF) and carbohydrate
      (CHO) on high-intensity intermittent sprints (HIS) performance and physiological
      responses. METHODS: Twelve active males underwent 4 interventions at least 7 days
      apart in a randomized, double-blind, placebo-controlled, balanced trial. A meal
      contained 65 % CHO was provided 2 h before the HIS test. Participants ingested
      the placebo (PLA) or CAF (6 mg kg(-1) BW) 1 h before taking an HIS test, and
      ingested a PLA or CHO solution (0.8 g kg(-1) BW) before undergoing the testing
      protocol. The HIS protocol comprised ten sets of 5 * 4-s sprints on a cycle
      ergometer with a 2-min recovery between each set. RESULTS: There was no
      significant difference between peak power output and mean power output between
      trials (p > 0.05). Compared with PLA, CAF + CHO resulted in a 5.2 % reduction in
      total work, corresponding to a 24.7-25.7 % increase in fatigue at the end stage
      of the HIS. The administration of CAF + CHO supplementation also resulted in an
      11.1 % increase in blood lactate, and elevated blood glucose concentrations
      throughout HIS testing compared with PLA (p < 0.05). Cortisol concentrations also
      increased with CAF + CHO intake compared with PLA; however, there was no
      significant effect of CAF + CHO supplementation on testosterone concentrations.
      CONCLUSION: Co-ingestion of CAF and CHO did not improve high-intensity sprint
      cycling performance or reduce fatigue in active males. Moreover, combined CAF and
      CHO supplementation might facilitate catabolism during prolonged high-intensity
      intermittent exercise.

PMID- 24748533
TI  - Coronary angioplasty for congenital obstruction of the left main coronary artery.
AB  - We present three children who underwent coronary angioplasty for the surgical
      treatment of a congenital obstruction of the left main coronary artery. An azygos
      vein patch or graft was a feasible and useful material for reconstructing
      congenital ostial stenosis and atresia of the left main coronary artery. 

PMID- 24748534
TI  - Regional apparent diffusion coefficient values in 3rd trimester fetal brain.
AB  - INTRODUCTION: Apparent diffusion coefficient (ADC) values in the developing fetus
      can be used in the diagnosis and prognosis of prenatal brain pathologies. To this
      end, we measured regional ADC in a relatively large cohort of normal fetal brains
      in utero. METHODS: Diffusion-weighted imaging (DWI) was performed in 48 non
      sedated 3rd trimester fetuses with normal structural MR imaging results. ADC was
      measured in white matter (frontal, parietal, temporal, and occipital lobes),
      basal ganglia, thalamus, pons, and cerebellum. Regional ADC values were compared
      by one-way ANOVA with gestational age as covariate. Regression analysis was used
      to examine gestational age-related changes in regional ADC. Four other cases of
      CMV infection were also examined. RESULTS: Median gestational age was 32 weeks
      (range, 26-33 weeks). There was a highly significant effect of region on ADC,
      whereby ADC values were highest in white matter, with significantly lower values
      in basal ganglia and cerebellum and the lowest values in thalamus and pons. ADC
      did not significantly change with gestational age in any of the regions tested.
      In the four cases with fetal CMV infection, ADC value was associated with a
      global decrease. CONCLUSION: ADC values in normal fetal brain are relatively
      stable during the third trimester, show consistent regional variation, and can
      make an important contribution to the early diagnosis and possibly prognosis of
      fetal brain pathologies.

PMID- 24748535
TI  - Prognosis associated with surgery for non-small cell lung cancer and synchronous
      brain metastasis.
AB  - PURPOSE: Several reports have described extended survival after aggressive
      surgical treatment for non-small cell lung cancer (NSCLC) and synchronous brain
      metastasis. This retrospective analysis assesses the prognostic factors in this
      population. METHODS: We reviewed retrospectively the medical records of 29
      patients with synchronous brain metastasis from NSCLC, who underwent surgical
      treatment in our institution between 1980 and 2008. All patients underwent chest
      surgery to remove the primary lesion. The impact of several variables on survival
      was assessed. RESULTS: The median follow-up period was 9.6 months and the 5-year
      survival rate from the time of lung cancer resection was 20.6 %. Univariate
      analysis demonstrated that the carcinoembryonic antigen (CEA) level, primary
      tumor size, and the presence of lymph node involvement were predictive of overall
      survival (p < 0.05). Multivariate analysis also identified those factors to be
      independent favorable prognostic factors. CONCLUSIONS: Although the survival of
      patients with brain metastasis from non-small cell lung cancer remains poor,
      surgical resection may benefit a select group of patients, particularly those
      with a normal CEA level, small tumor size, and node-negative status.

PMID- 24748536
TI  - An automated framework for NMR resonance assignment through simultaneous slice
      picking and spin system forming.
AB  - Despite significant advances in automated nuclear magnetic resonance-based
      protein structure determination, the high numbers of false positives and false
      negatives among the peaks selected by fully automated methods remain a problem.
      These false positives and negatives impair the performance of resonance
      assignment methods. One of the main reasons for this problem is that the
      computational research community often considers peak picking and resonance
      assignment to be two separate problems, whereas spectroscopists use expert
      knowledge to pick peaks and assign their resonances at the same time. We propose
      a novel framework that simultaneously conducts slice picking and spin system
      forming, an essential step in resonance assignment. Our framework then employs a
      genetic algorithm, directed by both connectivity information and amino acid
      typing information from the spin systems, to assign the spin systems to residues.
      The inputs to our framework can be as few as two commonly used spectra, i.e.,
      CBCA(CO)NH and HNCACB. Different from the existing peak picking and resonance
      assignment methods that treat peaks as the units, our method is based on
      'slices', which are one-dimensional vectors in three-dimensional spectra that
      correspond to certain ([Formula: see text]) values. Experimental results on both
      benchmark simulated data sets and four real protein data sets demonstrate that
      our method significantly outperforms the state-of-the-art methods while using a
      less number of spectra than those methods. Our method is freely available at
      http://sfb.kaust.edu.sa/Pages/Software.aspx.

PMID- 24748537
TI  - Bone marrow versus peripheral blood allogeneic haematopoietic stem cell
      transplantation for haematological malignancies in adults.
AB  - BACKGROUND: Allogeneic haematopoietic stem cell transplantation (allo-HSCT) is an
      established treatment option for many malignant and non-malignant disorders. In
      the past two decades, peripheral blood stem cells replaced bone marrow as stem
      cell source due to faster engraftment and practicability. Previous meta-analyses
      analysed patients treated from 1990 to 2002 and demonstrated no impact of the
      stem cell source on overall survival, but a greater risk for graft-versus-host
      disease (GvHD) in peripheral blood transplants. As transplant indications and
      conditioning regimens continue to change, whether the choice of the stem cell
      source has an impact on transplant outcomes remains to be determined. OBJECTIVES:
      To assess the effect of bone marrow versus peripheral blood stem cell
      transplantation in adult patients with haematological malignancies with regard to
      overall survival, incidence of relapse and non-relapse mortality, disease-free
      survival, transplant-related mortality, incidence of GvHD and time to
      engraftment. SEARCH METHODS: We searched the Cochrane Central Register of
      Controlled Trials (CENTRAL) (The Cochrane Library 2014, Issue 1), MEDLINE (from
      1948 to February 2014), trial registries and conference proceedings. The search
      was conducted in October 2011 and was last updated in February 2014. We did not
      apply any language restrictions. SELECTION CRITERIA: We included randomised
      controlled trials (RCTs) comparing bone marrow and peripheral blood allogeneic
      stem cell transplantation in adults with haematological malignancies. DATA
      COLLECTION AND ANALYSIS: Two review authors screened abstracts and extracted and
      analysed data independently. We contacted study authors for additional
      information. We used the standard methodological procedures expected by The
      Cochrane Collaboration. MAIN RESULTS: We included nine RCTs that met the pre
      defined selection criteria, involving a total of 1521 participants. Quality of
      data reporting was heterogeneous among the studies. Overall, the risk of bias in
      the included studies was low.For the primary outcome overall survival, our
      analysis demonstrated comparable results between bone marrow transplantation
      (BMT) and peripheral blood stem cell transplantation (PBSCT) (six studies, 1330
      participants; hazard ratio (HR) 1.07; 95% CI 0.91 to 1.25; P value = 0.43; high
      quality evidence).Disease-free survival (six studies, 1225 participants; HR 1.04;
      95% CI 0.89 to 1.21; P value = 0.6; moderate-quality of evidence) and non-relapse
      or transplant-related mortality (three studies, 758 participants; HR 0.98; 95% CI
      0.76 to 1.28; P = 0.91; high-quality evidence) were also comparable between
      transplantation arms.In the related-donor setting, data from two of eight studies
      with 211 participants (21%) indicated a higher relapse incidence in participants
      transplanted with bone marrow stem cells rather than peripheral blood stem cells
      (HR 2.73; 95% CI 1.47 to 5.08; P value = 0.001). There was no clear evidence of a
      difference in relapse incidence between transplantation groups in unrelated
      donors (HR 1.07; 95% CI 0.78 to 1.47; P value = 0.66). The difference between the
      donor-related and -unrelated subgroups (P-value = 0.008) was considered to be
      statistically significant.BMT was associated with lower rates of overall and
      extensive chronic GvHD than PBSCT (overall chronic GvHD: four studies, 1121
      participants; HR 0.72; 95% CI 0.61 to 0.85; P value = 0.0001, extensive chronic
      GvHD: four studies, 765 participants; HR 0.69; 95% CI 0.54 to 0.9; P value =
      0.006; moderate-quality evidence for both outcomes). The incidence of acute GvHD
      grades II to IV was not lower (six studies, 1330 participants; HR 1.03; 95% CI
      0.89 to 1.21; P value = 0.67; moderate-quality evidence), but there was a trend
      for a lower incidence of grades III and IV acute GvHD with BMT than with PBSCT
      (three studies, 925 participants; HR 0.75; 95% CI 0.55 to 1.02; P value = 0.07;
      moderate-quality evidence).Times to neutrophil and platelet engraftment were
      longer with BMT than with PBSCT (neutrophil: five studies, 662 participants; HR
      1.96; 95% CI 1.64 to 2.35; P value < 0.00001; platelet: four studies, 333
      participants; HR 2.17; 95% CI 1.69 to 2.78; P value < 0.00001). AUTHORS'
      CONCLUSIONS: This systematic review  found high-quality evidence that overall
      survival following allo-HSCT using the current clinical standard stem cell source
      - peripheral blood stem cells - was similar to that following allo-HSCT using
      bone marrow stem cells in adults with haematological malignancies. We found
      moderate-quality evidence that PBSCT was associated with faster engraftment of
      neutrophils and platelets, but a higher risk of GvHD (in terms of more overall
      and extensive chronic GvHD). There was an imprecise effect on relapse and on
      severe (grades III to IV) acute GvHD. Quality of life, which is severely affected
      by GvHD, was not evaluated.Against the background of transplantation practices
      that have clearly changed over the past 10 to 15 years, our aim was to provide
      current data on the best stem cell source for allo-HSCT, by including the results
      of recently conducted trials. Our review includes participants recruited up to
      2009, a proportion of whom were older, had received reduced-intensity
      conditioning regimens or had been transplanted with stem cells from unrelated
      donors. However, only one, large, study included relatively recently treated
      participants. Nevertheless, our findings are comparable to those of previous meta
      analyses suggesting that our results hold true for today's practice.

PMID- 24748538
TI  - Interleukins 15 and 12 in combination expand the selective loss of natural killer
      T cells in HIV infection in vitro.
AB  - The present study evaluated the frequency and receptor expression pattern of
      invariant natural killer T (iNKT) cells in human immunodeficiency virus (HIV)
      infected individuals. Further, the effect of IL-15 + IL-12 stimulation on iNKT
      cells was also assessed. The study included 15 individuals each from normal
      healthy subjects, pulmonary tuberculosis patients, HIV-infected individuals, and
      patients with HIV and tuberculosis coinfection (HIV-TB). The frequency of iNKT
      cells and the expression of phenotype, cytotoxic and chemokine receptors were
      studied by flow cytometry. The number of iNKT cells was significantly depleted in
      HIV and HIV-TB patients, which upon IL-15 + IL-12 stimulation expanded in HIV.
      The constitutively expressed natural cytotoxicity receptor, NKp46 was increased
      in HIV and HIV-TB, which might be the host's response to HIV replication. The
      distinct expression patterns of chemokine and adhesion receptors suggest that
      iNKT subsets might traffic to different microenvironment and tissues. High
      expression of chemokine receptor CCR5 by most iNKT cells suggests that these
      cells might be more favorable targets of HIV infection. Our results show that IL
      15 and IL-12 combination has the ability to expand the selective depletion of
      iNKT cells in vitro in HIV-infected individuals, but of limited value when
      coinfected with TB.

PMID- 24748539
TI  - Reproducibility, and age, body-weight and gender dependency of candidate skeletal
      muscle MRI outcome measures in healthy volunteers.
AB  - OBJECTIVES: Quantitative magnetic resonance imaging (MRI) can potentially meet
      the pressing need for objective, sensitive, reproducible outcome measures in
      neuromuscular disease trials. We tested, in healthy volunteers, the consistency,
      reliability and sensitivity to normal inter-subject variation of MRI methods
      targeted to lower limb muscle pathology to inform the design of practical but
      comprehensive MRI outcome measure protocols for use in imminent patient studies.
      METHODS: Forty-seven healthy volunteers, age 21-81 years, were subject at 3T to
      three-point Dixon fat-fraction measurement, T1-relaxometry, T2-relaxometry and
      magnetisation transfer ratio (MTR) imaging at mid-thigh and mid-calf level
      bilaterally. Fifteen subjects underwent repeat imaging at 2 weeks. RESULTS: Mean
      between-muscle fat fraction and T2 differences were small, but significant (p <
      0.001). Fat fraction and T 2 correlated positively, and MTR negatively with
      subject age in both the thigh and calf, with similar significant correlations
      with weight at thigh level only (p < 0.001 to p < 0.05). Scan-rescan and inter
      observer intra-class correlation coefficients ranged between 0.62-0.84 and 0.79
      0.99 respectively. CONCLUSIONS: Quantitative lower-limb muscle MRI using readily
      implementable methods was sensitive enough to demonstrate inter-muscle
      differences (small in health), and correlations with subject age and weight. In
      combination with high reliability, this strongly supports the suitability of
      these methods to provide longitudinal outcome measures in neuromuscular disease
      treatment trials. KEY POINTS: * Quantitative lower limb muscle MRI provides
      potential outcome measures in neuromuscular diseases * Bilateral thigh/calf
      coverage using sequences sensitive to acute and chronic pathology * Measurements
      have excellent scan-rescan and interobserver reliability * Measurements show
      small but significant inter-subject age and weight dependency * Readily
      implementable sequences suitable for further assessment in patient studies.

PMID- 24748540
TI  - Mechanisms of inorganic carbon acquisition in two estuarine Rhodophyceans:
      Bostrychia scorpioides (Hudson) ex Kutzing Montagne and Catenella caespitosa
      (Withering) L. M. Irvine.
AB  - Marine macroalgae possess a range of mechanisms to increase the availability of
      CO2 for fixation by ribulose-1,5-bisphosphate carboxylase/oxygenase. Of these,
      possession of a periplasmic or external carbonic anhydrase and the ability to use
      bicarbonate ions is widely distributed. The mechanisms of carbon acquisition were
      studied in two estuarine red macroalgae Bostrychia scorpioides and Catenella
      caespitosa using a range of techniques. pH-drift and CO2-depletion experiments at
      constant pH suggested that CO2 is the main source of inorganic carbon in both
      species. Inhibitors indicated that internal and external carbonic anhydrase were
      present in both species. Inhibitors also suggested that uptake of bicarbonate is
      unlikely to be present (P < 0.05). 

PMID- 24748541
TI  - HIC2 is a novel dosage-dependent regulator of cardiac development located within
      the distal 22q11 deletion syndrome region.
AB  - RATIONALE: 22q11 deletion syndrome arises from recombination between low-copy
      repeats on chromosome 22. Typical deletions result in hemizygosity for TBX1
      associated with congenital cardiovascular disease. Deletions distal to the
      typically deleted region result in a similar cardiac phenotype but lack in
      extracardiac features of the syndrome, suggesting that a second haploinsufficient
      gene maps to this interval. OBJECTIVE: The transcription factor HIC2 is lost in
      most distal deletions, as well as in a minority of typical deletions. We used
      mouse models to test the hypothesis that HIC2 hemizygosity causes congenital
      heart disease. METHODS AND RESULTS: We created a genetrap mouse allele of Hic2.
      The genetrap reporter was expressed in the heart throughout the key stages of
      cardiac morphogenesis. Homozygosity for the genetrap allele was embryonic lethal
      before embryonic day E10.5, whereas the heterozygous condition exhibited a
      partially penetrant late lethality. One third of heterozygous embryos had a
      cardiac phenotype. MRI demonstrated a ventricular septal defect with over-riding
      aorta. Conditional targeting indicated a requirement for Hic2 within the Nkx2.5+
      and Mesp1+ cardiovascular progenitor lineages. Microarray analysis revealed
      increased expression of Bmp10. CONCLUSIONS: Our results demonstrate a novel role
      for Hic2 in cardiac development. Hic2 is the first gene within the distal 22q11
      interval to have a demonstrated haploinsufficient cardiac phenotype in mice.
      Together our data suggest that HIC2 haploinsufficiency likely contributes to the
      cardiac defects seen in distal 22q11 deletion syndrome.

PMID- 24748542
TI  - Estimation of stature and sex from sternal lengths: an autopsy study.
AB  - The aim of this study was to derive regression equations for estimating stature
      and further to estimate sex from four measured sternal lengths. This study
      included intact sterna from 65 males and 30 females, aged between 25 and 40
      years, obtained during medico-legal autopsies. Stature and four sternal lengths,
      length of the manubrium (LM), length of the body (LB), length of the manubrium
      and body (LMB) and total sternal length, of each cadaver were measured. Stature
      and all measured sternal lengths were greater in males compared to females (p <
      0.001). All sternal lengths were positively correlated with stature in sexes. LMB
      had the highest correlation coefficient in both males and females (correlation
      coefficient: 0.721 and 0.740, respectively). In both sexes, linear regression
      analysis for stature estimation revealed equations with the highest R (2) values
      when derived from LMB (R (2) = 0.521 for males and R (2) = 0.547 for females). On
      the other hand, only the multiple linear regression equation derived from the
      combination of the LB and LMB had the higher R (2) value (R (2) = 0.640) for
      stature estimation in females. Receiver-operating curve analysis for all
      measurements was statistically significant (p < 0.05 for all). These findings
      suggested that measured sternal lengths can be used for estimation of sex.
      However, LB and LMB measurements were found to be the most reliable sternal
      lengths for estimating sex with an accuracy rate of 90 %. Our results revealed
      that the sternum is a useful tool for estimating stature and sex when other
      skeletal bones are not available.

PMID- 24748543
TI  - Current strategies for immunosuppression following liver transplantation.
AB  - BACKGROUND: New strategies for immunosuppression (IS) after liver transplantation
      (LTx) are in part responsible for the increased patient and graft survival seen
      over time. With a few basic exceptions-notably the continued use of steroids and
      calcineurin inhibitors (CNIs)-IS drugs and regimens being used today are
      different from those used 30 years ago. While graft loss due to acute or chronic
      rejection has become rare, the side effect burden of IS drugs exerts a
      significant toll on patients. CONCEPTS/TRENDS: CNIs continue to form the backbone
      of IS regimens, although their use is hampered by nephrotoxicity and other
      adverse effects. Consequently, a variety of CNI reduction or withdrawal
      strategies have formed the basis of clinical trials or entered into clinical
      practice. These trials have included the use of everolimus, an mTOR inhibitor,
      and anti-interleukin-2 receptor antibodies. Basiliximab, as well as other
      lymphocyte nondepleting and depleting agents, have shown benefit in induction
      regimens. SUMMARY: Along with steroid reduction or elimination, current
      strategies for IS after LTx continue to explore novel combinations of agents,
      with an aim toward striking a balance between diminution of rejection and the
      need for avoiding adverse effects of the IS drugs. Long-term maintenance
      strategies are also discussed in this review, as is development of tolerance and
      antibody-mediated rejection.

PMID- 24748544
TI  - Management of paediatric tibial fractures using two types of circular external
      fixator: Taylor spatial frame and Ilizarov circular fixator.
AB  - BACKGROUND: The use of circular fixators for the treatment of tibial fractures is
      well established in the literature. The aim of this study was to compare the
      Ilizarov circular fixator (ICF) with the Taylor spatial frame (TSF) in terms of
      treatment results in consecutive patients with tibial fractures that required
      operative management. METHOD: A retrospective analysis of patient records and
      radiographs was performed to obtain patient data, information on injury
      sustained, the operative technique used, time duration in frame, healing time and
      complications of treatment. The minimum follow-up was 24 months. RESULTS: Ten
      patients were treated with ICF between 2000 and 2005, while 15 patients have been
      treated with TSF since 2005. Two of the 10 treated with ICF and 5 of the 15
      treated with TSF were open fractures. All patients went on to achieve complete
      union. Mean duration in the frame was 12.7 weeks for ICF and 14.8 weeks for the
      TSF group. Two patients in the TSF group had delayed union and required
      additional procedures including adjustment of fixator and bone grafting. There
      was one malunion in the TSF group that required osteotomy and reapplication of
      frame. There were seven and nine pin-site infections in the ICF and TSF groups,
      respectively, all of which responded to antibiotics. There were no refractures in
      either group. CONCLUSION: In an appropriate patient, both types of circular
      fixator are equally effective but have different characteristics, with TSF
      allowing for postoperative deformity correction. Of concern are the two cases of
      delayed union in the TSF group, all in patients with high-energy injuries. We
      feel another larger study is required to provide further clarity in this matter.
      LEVEL OF EVIDENCE: Level II-comparative study.

PMID- 24748545
TI  - Activation of frontoparietal attention networks by non-predictive gaze and arrow
      cues.
AB  - Gaze and arrow cues automatically orient visual attention, even when they have no
      predictive value, but the neural circuitry by which they direct attention is not
      clear. Recent evidence has indicated that the ventral frontoparietal attention
      network is primarily engaged by breaches of a viewer's cue-related expectations.
      Accordingly, we hypothesized that to the extent that non-predictive gaze and
      arrow cues automatically engender expectations with regard to cue location, they
      should activate the ventral attention network when they cue attention invalidly.
      Using event-related fMRI, we found that invalid gaze but not arrow cues activated
      the ventral attention network, specifically in the area of the right temporal
      parietal junction (TPJ), as well as nodes along the dorsal attention network
      associated with a redirection of attention to the correct target location. In
      additional whole-brain analyses, facilitation of behavioral response time by
      valid gaze cues was linearly associated with the degree of activation in the
      right TPJ. We conclude from our findings that gaze direction elicits potent
      expectations in humans with regard to an actor's intention that engage attention
      networks if not differently from, at least more robustly than, arrow cues. 

PMID- 24748546
TI  - Reducing aggressive responses to social exclusion using transcranial direct
      current stimulation.
AB  - A vast body of research showed that social exclusion can trigger aggression.
      However, the neural mechanisms involved in regulating aggressive responses to
      social exclusion are still largely unknown. Transcranial direct current
      stimulation (tDCS) modulates the excitability of a target region. Building on
      studies suggesting that activity in the right ventrolateral pre-frontal cortex
      (rVLPFC) might aid the regulation or inhibition of social exclusion-related
      distress, we hypothesized that non-invasive brain polarization through tDCS over
      the rVLPFC would reduce behavioral aggression following social exclusion.
      Participants were socially excluded or included while they received tDCS or sham
      stimulation to the rVLPFC. Next, they received an opportunity to aggress.
      Excluded participants demonstrated cognitive awareness of their inclusionary
      status, yet tDCS (but not sham stimulation) reduced their behavioral aggression.
      Excluded participants who received tDCS stimulation were no more aggressive than
      included participants. tDCS stimulation did not influence socially included
      participants' aggression. Our findings provide the first causal test for the role
      of rVLPFC in modulating aggressive responses to social exclusion. Our findings
      suggest that modulating activity in a brain area (i.e. the rVLPFC) implicated in
      self-control and emotion regulation can break the link between social exclusion
      and aggression. 

PMID- 24748547
TI  - Positive selection on MHC class II DRB and DQB genes in the bank vole (Myodes
      glareolus).
AB  - The major histocompatibility complex (MHC) class IIB genes show considerable
      sequence similarity between loci. The MHC class II DQB and DRB genes are known to
      exhibit a high level of polymorphism, most likely maintained by parasite-mediated
      selection. Studies of the MHC in wild rodents have focused on DRB, whilst DQB has
      been given much less attention. Here, we characterised DQB genes in Swedish bank
      voles Myodes glareolus, using full-length transcripts. We then designed primers
      that specifically amplify exon 2 from DRB (202 bp) and DQB (205 bp) and
      investigated molecular signatures of natural selection on DRB and DQB alleles.
      The presence of two separate gene clusters was confirmed using BLASTN and
      phylogenetic analysis, where our seven transcripts clustered according to either
      DQB or DRB homologues. These gene clusters were again confirmed on exon 2 data
      from 454-amplicon sequencing. Our DRB primers amplify a similar number of alleles
      per individual as previously published DRB primers, though our reads are longer.
      Traditional d N/d S analyses of DRB sequences in the bank vole have not found a
      conclusive signal of positive selection. Using a more advanced substitution model
      (the Kumar method) we found positive selection in the peptide binding region
      (PBR) of both DRB and DQB genes. Maximum likelihood models of codon substitutions
      detected positively selected sites located in the PBR of both DQB and DRB.
      Interestingly, these analyses detected at least twice as many positively selected
      sites in DQB than DRB, suggesting that DQB has been under stronger positive
      selection than DRB over evolutionary time.

PMID- 24748548
TI  - Region-specific DNA alterations in focally induced seizures.
AB  - We induced brief secondarily generalized seizures of limbic origin in Sprague
      Dawley rats by bicuculline microinfusion into the anterior piriform cortex. After
      1 h or 5 days we performed comet assay, a sensitive marker for DNA damage, within
      entorhinal cortex, hippocampus (limbic areas recruited by seizure spreading) and
      striatum (which is not recruited). DNA damage occurred selectively in the
      ipsilateral entorhinal cortex and hippocampus at 1 h, but not at 5 days. These
      data shed new light on molecular genetics as a marker during limbic seizures, the
      most common in epileptic patients. 

PMID- 24748549
TI  - Application of an OCT data-based mathematical model of the foveal pit in
      Parkinson disease.
AB  - Spectral-domain Optical coherence tomography (OCT) has shown remarkable utility
      in the study of retinal disease and has helped to characterize the fovea in
      Parkinson disease (PD) patients. We developed a detailed mathematical model based
      on raw OCT data to allow differentiation of foveae of PD patients from healthy
      controls. Of the various models we tested, a difference of a Gaussian and a
      polynomial was found to have "the best fit". Decision was based on mathematical
      evaluation of the fit of the model to the data of 45 control eyes versus 50 PD
      eyes. We compared the model parameters in the two groups using receiver-operating
      characteristics (ROC). A single parameter discriminated 70 % of PD eyes from
      controls, while using seven of the eight parameters of the model allowed 76 % to
      be discriminated. The future clinical utility of mathematical modeling in study
      of diffuse neurodegenerative conditions that also affect the fovea is discussed. 

PMID- 24748550
TI  - Real-time two-dimensional and three-dimensional echocardiographic imaging of the
      thoracic spinal cord: a possible new window into the central neuraxis.
AB  - Transesophageal echocardiography of the spine has been difficult to perform, and
      high-quality images have been difficult to obtain with earlier available
      technology. New capabilities in hardware and software reconstruction may allow
      more reliable clinical data to be obtained. We describe an initial successful
      attempt to image the adult spinal canal, its contents, and in situ
      instrumentation. This report is a retrospective review of two patients in whom
      transesophageal echocardiography (TEE) was used to image the thoracic spine. The
      thoracic spine was identified and imaged with real-time 2-D and 3-D technology
      with location of the thoracic aorta and slight insertion and withdrawal of the
      TEE probe until the intervertebral discs alignment was optimized. Images of the
      spinal cord anatomy and its vascular supply, as well as indwelling epidural
      catheters were easily identified. 2-D and 3-D imaging was performed and images
      were recorded in digital imaging and communications in medicine format. 3-D
      reconstruction of images was possible with instantaneous 3-D imaging from
      multiple 2-D electrocardiogram-gated image acquisitions using the Phillips TEE IE
      33 imaging platform. The central neuraxial cavity, including the spinal cord and
      the spinal nerve roots, was easily visualized, and motion of the cord was seen in
      a phasic pattern (with respiratory variation); cerebrospinal fluid surrounding
      the spinal cord was documented. The epidural space and local anesthetic drug
      administration through the epidural catheter were visualized, with the epidural
      catheter seen lying adjacent to the epidural tissue as a bright hyperechoic line.
      Pulsed-wave Doppler determined a biphasic pattern of blood flow in the anterior
      spinal artery through pulse mapping of the anatomic area. New, advanced imaging
      hardware and software generate clinically useful imaging of the thoracic spine in
      2-D and 3-D using TEE. We believe this technology holds promise for future
      diagnostic and therapeutic interventions in the operating room that were
      previously unavailable. 

PMID- 24748551
TI  - The effect of endotracheal tube cuff pressure change during gynecological
      laparoscopic surgery on postoperative sore throat: a control study.
AB  - Postoperative respiratory complications related to endotracheal intubation
      usually present as cough, sore throat, hoarseness. The aim of the study was to
      examine the effects of endotracheal tube cuff pressure changes during
      gynecological laparoscopic surgery on postoperative sore throat rates. Thirty
      patients who underwent gynecological laparoscopic surgery and 30 patients who
      underwent laparotomy under general anesthesia with endotracheal intubation were
      included. After induction of general anesthesia and endotracheal intubation, the
      cuff was inflated to 25 mmHg. At 5, 15, 30, 45 and 60 min after endotracheal
      intubation, cuff pressure and peak airway pressure were recorded. At 2 and 24 h
      after surgery, the patients were assessed for complaints of a sore throat. In
      patients who underwent laparotomy, cuff pressure and peak airway pressure did not
      change significantly at different time points after intubation. In patients who
      received laparoscopic surgery, cuff pressure and peak airway pressure were
      significantly increased compared to initial pressure at all examined time points.
      In both groups, the endotracheal tube cuff pressure and peak airway pressure were
      significantly correlated (R=0.9431, P<0.01; R=0.8468, P<0.01). Compared to
      patients who had undergone laparotomy, patients who had undergone laparoscopic
      surgery showed significantly higher sore throat scores at both 2 and 24 h after
      surgery (P<0.01). Pneumoperitoneum and Trendelenburg position may increase airway
      pressure and cuff pressure, resulting in increased incidence of postoperative
      sore throat.

PMID- 24748552
TI  - CXCR4 is highly expressed at the tumor front but not in the center of prostate
      cancers.
AB  - OBJECTIVE: To evaluate the expression of CXCR4, its ligand SDF-1, beta-catenin
      and E-cadherin throughout the local tumor microenvironment of prostate cancer.
      PATIENTS AND METHODS: A total of 64 prostate cancer specimens, 24 frozen and 40
      paraffin-embedded sections, were obtained from patients treated with radical
      prostatectomy for clinically localized cancer. Real-time RT-PCR was used for mRNA
      quantification of CXCR4 and SDF-1 in the tumor center (T), tumor front (F) and
      distant peritumoral tissue (D). Immunohistochemical analysis was used to
      investigate the expression patterns of CXCR4, E-cadherin and beta-catenin.
      Clinical records of these patients were studied for follow-up data, and the
      prognostic value of these molecules' expression was statistically assessed.
      RESULTS: CXCR4 mRNA and protein were significantly increased at the tumor front
      as compared to distant tissue or tumor center. In comparison, SDF-1 mRNA level
      gradually increased from the tumor center to the distant peritumoral tissue. High
      CXCR4 at the tumor front was associated with high Gleason score. Low SDF-1 at the
      tumor front was associated with locally advanced cancer and disease recurrence.
      Moreover, high CXCR4 staining at the tumor front and increased cytosolic E
      cadherin expression in the same location was associated with locally advanced
      disease. CONCLUSIONS: CXCR4 seems overexpressed at the tumor front of prostate
      tumors, where it potentially promotes cell migration toward the SDF-1 centrifugal
      attracting gradient, as well as epithelial-mesenchymal transition. High CXCR4 and
      low SDF-1 levels at tumor front were both associated with adverse histological
      features.

PMID- 24748553
TI  - Arabidopsis thaliana PDX1.2 is critical for embryo development and heat shock
      tolerance.
AB  - MAIN CONCLUSION: PDX1.2 is expressed in the basal part of the globular-stage
      embryo, and plays critical roles in development, hypocotyl elongation, and stress
      response. The Arabidopsis thaliana PDX1.2 protein belongs to a small family of
      three members. While PDX1.1 and PDX1.3 have been extensively described and are
      well established to function in vitamin B6 biosynthesis, the biological role of
      PDX1.2 still remains elusive. Here, we show that PDX1.2 is expressed early in
      embryo development, and that heat shock treatment causes a strong up-regulation
      of the gene. Using a combined genetic approach of T-DNA insertion lines and
      expression of artificial micro RNAs, we can show that PDX1.2 is critically
      required for embryo development, and for normal hypocotyl elongation. Plants with
      reduced PDX1.2 expression also display reduced primary root growth after heat
      shock treatments. The work overall provides a set of important new findings that
      give greater insights into the developmental role of PDX1.2 in plants.

PMID- 24748554
TI  - Accelerated approval for pertuzumab in the neoadjuvant setting: winds of change?
AB  - Accelerated approval for agents that improve the frequency of complete pathologic
      response in the primary breast cancer setting heralds a broadening of the
      opportunities to get effective agents to the market more quickly. However, these
      new pathways will require identifying the signature or subtype for which the
      agent is most effective, and evidence of enrollment of patients to a trial that
      enables the ascertainment of event-free survival. The recent approval of
      pertuzumab for use in the neoadjuvant setting is evidence that the FDA is
      committed to supporting the accelerated approval pathway. The situations in which
      approval is likely to be granted are discussed.

PMID- 24748555
TI  - Adjustment disorder: new developments.
AB  - Adjustment disorders (ADs) have been included in the psychiatric classifications
      since 1952 although their name has changed over time. In DSM 5 they have been
      classified under the trauma and stress related disorders for the first time.
      Despite this positive step, there are still problems with the classification of
      ADs. There is no guidance on the distinction from normal stress reactions, it
      remains a subthreshold category, and the subtypes are not strongly underpinned by
      research. There are no specific diagnostic criteria in terms of symptom numbers
      or combinations of these, unlike most other conditions classified in DSM. Apart
      from epidemiological studies in those with medical illnesses, recent prevalence
      studies in other populations are scarce. Research is lacking in many aspects of
      AD, especially their biological underpinnings and treatments. One factor
      contributing to this is the absence of adequate diagnostic interview schedules.
      Interest in ADs may increase now that they are classified with the trauma-related
      group of disorders. 

PMID- 24748557
TI  - Assessing quality of life in patients with prostate cancer: a systematic and
      standardized comparison of available instruments.
AB  - PURPOSE: The objective was to obtain a standardized evaluation of available
      prostate cancer-specific quality of life instruments used in patients with early
      stage disease. METHODS: We carried out systematic literature reviews in the
      PubMed database to identify manuscripts which contained information regarding
      either the development process or metric properties of prostate cancer-specific
      quality of life instruments. Each instrument was evaluated by two experts,
      independently, using the Evaluating Measures of Patient-Reported Outcomes (EMPRO)
      tool. An overall and seven attribute-specific EMPRO scores were calculated (range
      0-100, worst to best): measurement model, reliability, validity, responsiveness,
      interpretability, burden and alternative forms. RESULTS: Eight instruments and 57
      manuscripts (2-15 per instrument) were identified. The Expanded Prostate Cancer
      Index Composite (EPIC) was the best rated (overall EMPRO score 83.1 points). Good
      results were also obtained by University of California Los Angeles-Prostate
      Cancer Index (UCLA-PCI), Patient-Oriented Prostate Utility Scale (PORPUS) and
      Prostate Cancer Quality of Life Instrument (PC-QoL) with 77.3, 70.5 and 64.8
      points, respectively. These four instruments passed with distinction the validity
      and responsiveness evaluation. Insufficient reliability results were observed for
      UCLA-PCI and PORPUS. CONCLUSIONS: Current evidence supports the choice of EPIC,
      PORPUS or PC-QoL. Attribute-specific EMPRO results facilitate selecting the
      adequate instrument for every purpose. For longitudinal studies or clinical
      trials, where responsiveness is the priority, EPIC or PC-QoL should be
      considered. We recommend the PORPUS for economic evaluations because it allows
      cost-utility analysis, and EPIC short versions to minimize administration burden.

PMID- 24748558
TI  - The effects of anxiety sensitivity, pain hypervigilance, and pain catastrophizing
      on quality of life outcomes of patients with chronic pain: a preliminary, cross
      sectional analysis.
AB  - PURPOSE: In the fear-avoidance model (FAM) of chronic pain, pain-related fear is
      one of the most prominent predictors of negative adjustment outcomes. While
      existing data point to the effects of anxiety sensitivity, pain hypervigilance,
      and pain catastrophizing on pain-related fear, the nature of their multivariate
      relationships remains unclear. This study explored the possible mediating role of
      pain hypervigilance in the relationship of anxiety sensitivity and pain
      catastrophizing with pain-related fear, and their effects on quality of life
      (QoL) outcomes within the FAM framework. METHODS: A sample of 401 Chinese
      patients with chronic musculoskeletal pain completed the standardized measures
      assessing the FAM components and QoL. Structural equation modeling (SEM) was used
      to evaluate six hypothesized models. RESULTS: Results of SEM showed adequate data
      model fit [comparative fit indexes (CFIs) ranging from 0.92 to 0.94] on models
      which specified pain hypervigilance as mediator of anxiety sensitivity and pain
      catastrophizing with pain-related fear on two QoL outcomes (QoL-Physical and QoL
      Mental). Results consistent with net suppression effects of pain catastrophizing
      on anxiety sensitivity were found in SEM when both anxiety sensitivity and pain
      catastrophizing were included in the same full model to predict QoL-Physical (CFI
      = 0.95; Sobel z = 8.06, p < 0.001) and QoL-Mental (CFI = 0.93; Sobel z = 8.31, p
      < 0.001). CONCLUSIONS: These cross-sectional analyses gave results consistent
      with pain hypervigilance, mediating the relationship of pain catastrophic
      cognition and anxiety sensitivity with pain-related fear. The net suppression
      effects of pain catastrophizing point to anxiety sensitivity, enhancing the
      effect of pain catastrophic cognition on pain hypervigilance. These findings
      elucidate how the interdependence of dispositional factors might influence pain
      adjustment and functioning.

PMID- 24748559
TI  - Relationships between divided attention and working memory impairment in people
      with schizophrenia.
AB  - Recent studies suggest that people with schizophrenia (PSZ) have difficulty
      distributing their attention broadly. Other research suggests that PSZ have
      reduced working memory (WM) capacity. This study tested whether these findings
      reflect a common underlying deficit. We measured the ability to distribute
      attention by means of the Useful Field of View (UFOV) task, in which participants
      must distribute attention so that they can discriminate a foveal target and
      simultaneously localize a peripheral target. Participants included 50 PSZ and 52
      healthy control subjects. We found that PSZ exhibited severe impairments in UFOV
      performance, that UFOV performance was highly correlated with WM capacity in PSZ
      (r = -.61), and that UFOV impairments could not be explained by either impaired
      low-level processing or a generalized deficit. These results suggest that a
      common mechanism explains deficits in the ability to distribute attention
      broadly, reduced WM capacity, and other aspects of impaired cognition in
      schizophrenia. We hypothesize that this mechanism may involve abnormal local
      circuit dynamics that cause a hyperfocusing of resources onto a small number of
      internal representations. 

PMID- 24748561
TI  - Interneurons, tau and amyloid-beta in the piriform cortex in Alzheimer's disease.
AB  - Impaired olfaction has been described as an early symptom of Alzheimer's disease.
      Neuroanatomical changes underlying this deficit in the olfactory system are
      largely unknown. Interestingly, neuropathology begins in the transentorhinal
      cortex and extends to the neighboring limbic system and basal telencephalic
      structures that mediate olfactory processing, including the anterior olfactory
      nucleus and olfactory bulb. The human piriform cortex has been described as a
      crucial area in odor quality coding; disruption of this region mediates early
      olfactory deficits in Alzheimer's disease. Most neuropathological investigations
      have focused on the entorhinal cortex and hippocampus, whereas the piriform
      cortex has largely been neglected. This work aims to characterize the expression
      of the neuropathological amyloid-beta peptide, tau protein and interneuron
      population markers (calretinin, parvalbumin and somatostatin) in the piriform
      cortex of ten Alzheimer-diagnosed (80.4 +/- 8.3 years old) and five control (69.6
      +/- 11.1) cases. Here, we examined the distribution of different interneuronal
      markers as well as co-localization of interneurons and pathological markers.
      Results indicated preferential vulnerability of somatostatin- (p = 0.0001 < alpha
      = 0.05) and calretinin-positive (p = 0.013 < alpha = 0.05) cells that colocalized
      with amyloid-beta peptide, while the prevalence of parvalbumin-positive cells was
      increased (p = 0.045 < alpha = 0.05) in the Alzheimer's cases. These data may
      help to reveal the neural basis of olfactory deficits linked to Alzheimer's
      disease as well as to characterize neuronal populations preferentially vulnerable
      to neuropathology in regions critically involved in early stages of the disease.

PMID- 24748562
TI  - The metabolic drug-drug interaction profile of Dabrafenib: in vitro
      investigations and quantitative extrapolation of the P450-mediated DDI risk.
AB  - Dabrafenib is a potent ATP-competitive inhibitor for the V600 mutant b-rapidly
      accelerated fibrosarcoma (b-raf) kinase currently approved in the United States
      for the treatment of metastatic melanoma. Studies were conducted in human liver
      microsomes, recombinant human cytochrome P450 (P450) enzymes, and human
      hepatocytes to investigate the potential of dabrafenib and its major circulating
      metabolites to perpetrate pharmacokinetic drug-drug interactions (DDIs) as well
      as have their own pharmacokinetics affected (victim) by coadministered drugs.
      Dabrafenib metabolism was mediated by CYP2C8 (56% to 67%) and CYP3A4 (24%); in
      addition, it has demonstrated inhibition of CYP2C8, 2C9, 2C19, 3A4
      (atorvastatin), and (nifedipine), with calculated IC50 values of 8.2, 7.2, 22.4,
      16, and 32 MUM. It also demonstrated metabolism-dependent inhibition of CYP3A4
      with a maximal inactivation rate constant of 0.040 minute(-1) and a concentration
      required to achieve half-maximal inactivation for CYP3A4 of 38 MUM. Hydroxy
      dabrafenib inhibited CYP1A2, 2C9, and 3A4 (midazolam) with calculated IC50 values
      of 83, 29, and 44 MUM, and carboxy-dabrafenib did not inhibit any of the P450
      enzymes tested. Desmethyl-dabrafenib inhibited CYP2B6, 2C8, 2C9, 2C19, and 3A4
      (midazolam, atorvastatin, and nifedipine) with calculated IC50 values of 78, 47,
      6.3, 36, 17, 20, and 28 MUM, respectively. At 30 MUM dabrafenib showed increases
      in CYP2B6 and CYP3A4 mRNA expression indicative of induction. The potential
      clinical relevance of these findings was explored by using mechanistic static
      mathematical models to estimate the magnitude of change (area under the curve
      change) as a result of P450-mediated DDI interactions. This risk-assessment
      approach indicated that dabrafenib is unlikely to perpetrate any in vivo DDIs by
      inhibition mechanisms, but is a likely inducer of CYP3A4 and a victim of CYP3A4
      and CYP2C8 inhibitors. Furthermore, inclusion of the in vitro drug interaction
      data for dabrafenib metabolites did not impact the overall clinical risk
      assessment. 

PMID- 24748560
TI  - Pre-existing astrocytes form functional perisynaptic processes on neurons
      generated in the adult hippocampus.
AB  - The adult dentate gyrus produces new neurons that morphologically and
      functionally integrate into the hippocampal network. In the adult brain, most
      excitatory synapses are ensheathed by astrocytic perisynaptic processes that
      regulate synaptic structure and function. However, these processes are formed
      during embryonic or early postnatal development and it is unknown whether
      astrocytes can also ensheathe synapses of neurons born during adulthood and, if
      so, whether they play a role in their synaptic transmission. Here, we used a
      combination of serial-section immuno-electron microscopy, confocal microscopy,
      and electrophysiology to examine the formation of perisynaptic processes on adult
      born neurons. We found that the afferent and efferent synapses of newborn neurons
      are ensheathed by astrocytic processes, irrespective of the age of the neurons or
      the size of their synapses. The quantification of gliogenesis and the
      distribution of astrocytic processes on synapses formed by adult-born neurons
      suggest that the majority of these processes are recruited from pre-existing
      astrocytes. Furthermore, the inhibition of astrocytic glutamate re-uptake
      significantly reduced postsynaptic currents and increased paired-pulse
      facilitation in adult-born neurons, suggesting that perisynaptic processes
      modulate synaptic transmission on these cells. Finally, some processes were found
      intercalated between newly formed dendritic spines and potential presynaptic
      partners, suggesting that they may also play a structural role in the
      connectivity of new spines. Together, these results indicate that pre-existing
      astrocytes remodel their processes to ensheathe synapses of adult-born neurons
      and participate to the functional and structural integration of these cells into
      the hippocampal network. 

PMID- 24748563
TI  - Prevaccine era human papillomavirus types 6, 11, 16 and 18 seropositivity in the
      U.S.A., National Health and Nutrition Examination Surveys, 2003-2006.
AB  - BACKGROUND: A vaccine is available to prevent human papillomavirus (HPV) 6, 11,
      16 and 18; in the prevaccine era, seropositivity to vaccine types is a measure of
      natural exposure. METHODS: We describe HPV seropositivity in the USA among 14-59
      year-olds using the 2003-2006 National Health and Nutrition Examination Surveys.
      RESULTS: Seropositivity to HPV 6, 11, 16 and 18 was 17.5%, 6.8%, 15.1% and 5.9%,
      respectively, among women, and 7.0%, 2.4%, 5.2% and 1.5%, respectively, among
      men. Overall in both sexes, seropositivity was 22.5% for any vaccine type (31.8%
      in women and 12.9% in men), but substantially lower for three or more types (1.7%
      overall, 2.8% in women and 0.6% in men). CONCLUSIONS: Almost a quarter of the
      participants were seropositive to any HPV vaccine type but few were seropositive
      to at least three vaccine HPV types in the prevaccine era. Further study is
      needed to assess if seropositivity would be useful as a biological marker of
      vaccination.

PMID- 24748564
TI  - The many "faces" of copper in medicine and treatment.
AB  - Copper (Cu) is an essential microelement found in all living organisms with the
      unique ability to adopt two different redox states-in the oxidized (Cu(2+)) and
      reduced (Cu(+)). It is required for survival and serves as an important catalytic
      cofactor in redox chemistry for proteins that carry out fundamental biological
      functions, important in growth and development. The deficit of copper can result
      in impaired energy production, abnormal glucose and cholesterol metabolism,
      increased oxidative damage, increased tissue iron (Fe) accrual, altered structure
      and function of circulating blood and immune cells, abnormal neuropeptides
      synthesis and processing, aberrant cardiac electrophysiology, impaired myocardial
      contractility, and persistent effects on the neurobehavioral and the immune
      system. Increased copper level has been found in several disorders like e.g.:
      Wilson's disease or Menke's disease. New findings with the great potential for
      impact in medicine include the use of copper-lowering therapy for
      antiangiogenesis, antifibrotic and anti-inflammatory purposes. The role of copper
      in formation of amyloid plaques in Alzheimer's disease, and successful treatment
      of this disorder in rodent model by copper chelating are also of interest. In
      this work we will try to describe essential aspects of copper in chosen diseases.
      We will represent the evidence available on adverse effect derived from copper
      deficiency and copper excess. We will try to review also the copper biomarkers
      (chosen enzymes) that help reflect the level of copper in the body. 

PMID- 24748566
TI  - The Effect of a Donor Milk Policy on the Diet of Very Low Birth Weight Infants.
AB  - BACKGROUND: Use of donor milk (DM) to supplement mother's own milk (MOM) in the
      neonatal intensive care unit (NICU) is steadily increasing based on health and
      developmental benefits to premature infants. A paucity of data exists documenting
      the effect of DM use on the diet of very low birth weight (VLBW) infants related
      to the implementation of a DM policy. OBJECTIVE: This study aimed to compare VLBW
      enteral intake type in the first 28 days of life before versus after establishing
      a DM policy. METHODS: This single-center pre-post prospective cohort study
      included all inborn infants <= 1500 grams in a level 4 NICU remaining
      hospitalized at 28 days and admitted either before (pre-DM period, October 2009
      March 2010) or after (DM period, October 2010-September 2012) implementing a DM
      policy. The feeding protocol was unchanged in both periods. Collected data
      included maternal/infant demographics, infant clinical data, and daily volume of
      enteral intake as MOM, DM, and formula. The proportion of enteral feeds from
      these sources during the first 28 days of life was compared pre-DM versus DM.
      RESULTS: Compared to pre-DM baseline, formula exposure was significantly
      decreased, and human milk exposure and proportion of diet as human milk
      increased. The proportion of infants fed exclusively human milk increased.
      Exposure to and proportion of diet as MOM was unchanged. Infants were fed earlier
      in the DM period. CONCLUSION: Establishment of a DM policy was associated with
      reduced exposure to formula, promoting an exclusively human milk diet, with
      earlier initiation of feeds and no decrease in use of MOM.

PMID- 24748565
TI  - Expert position paper on the management of antiplatelet therapy in patients
      undergoing coronary artery bypass graft surgery.

PMID- 24748567
TI  - Hereditary breast and ovarian cancer and reproduction: an observational study on
      the suitability of preimplantation genetic diagnosis for both asymptomatic
      carriers and breast cancer survivors.
AB  - Preimplantation genetic diagnosis (PGD) is a reproductive option for BRCA1/2
      mutation carriers wishing to avoid transmission of the predisposition for
      hereditary breast and ovarian cancer (HBOC) to their offspring. Embryos obtained
      by in vitro fertilisation (IVF/ICSI) are tested for the presence of the mutation.
      Only BRCA-negative embryos are transferred into the uterus. The suitability and
      outcome of PGD for HBOC are evaluated in an observational cohort study on
      treatments carried out in two of Western-Europe's largest PGD centres from 2006
      until 2012. Male carriers, asymptomatic female carriers and breast cancer
      survivors were eligible. If available, PGD on embryos cryopreserved before
      chemotherapy was possible. Generic PGD-PCR tests were developed based on
      haplotyping, if necessary combined with mutation detection. 70 Couples underwent
      PGD for BRCA1/2. 42/71 carriers (59.2 %) were female, six (14.3 %) of whom have
      had breast cancer prior to PGD. In total, 145 PGD cycles were performed. 720
      embryos were tested, identifying 294 (40.8 %) as BRCA-negative. Of fresh IVF/PGD
      cycles, 23.9 % resulted in a clinical pregnancy. Three cycles involved PGD on
      embryos cryopreserved before chemotherapy; two of these women delivered a healthy
      child. Overall, 38 children were liveborn. Two BRCA1 carriers were diagnosed with
      breast cancer shortly after PGD treatment, despite negative screening prior to
      PGD. PGD for HBOC proved to be suitable, yielding good pregnancy rates for
      asymptomatic carriers as well as breast cancer survivors. Because of two cases of
      breast cancer shortly after treatment, maternal safety of IVF(PGD) in female
      carriers needs further evaluation.

PMID- 24748568
TI  - Surgical excision of radial scars diagnosed by core biopsy may help predict
      future risk of breast cancer.
AB  - Radial scars (RS's) are benign breast lesions known to be associated with
      carcinomas and other high-risk lesions (HRL's). The upgrade rate to carcinoma
      after core biopsy revealing RS is 0-40 %. We sought to determine the outcomes of
      RS with and without HRL diagnosed by core biopsy. Patients who underwent core
      biopsy revealing RS without carcinoma at our institution between 1/1996 and
      11/2012 were identified from a surgical pathology database. Retrospective chart
      review was utilized to classify patients as RS-no HRL or RS-HRL. HRL was defined
      as ADH, LCIS, and/or ALH. We determined upgrade rate to carcinoma at surgical
      excision, and upgrade to HRL for RS-no HRL patients. Univariate analysis was
      performed to identify risk factors for upgrade in RS-no HRL patients. 156
      patients underwent core biopsy revealing RS, 131 RS-no HRL (84 %), and 25 RS-HRL
      (16 %). The overall rate of upgrade to invasive carcinoma was 0.8 % (1/124). 1.0
      % (1/102) of RS-no HRL and 13.6 % (3/22) of RS-HRL patients were upgraded to DCIS
      (P = 0.0023). The upgrade of RS-no HRL to HRL at excision was 21.6 % (22/102). By
      univariate analysis, RS-no HRL with radiologic appearance of a mass/architectural
      distortion had a significantly higher rate of upgrade to HRL or carcinoma
      compared with calcifications (P = 0.03). Excision of RS to rule out associated
      invasive carcinoma is not warranted, given a <1 % rate of upgrade at excision.
      However, excision to evaluate for non-invasive cancer or HRL may be considered to
      help guide clinical decision-making about use of chemoprevention. 

PMID- 24748569
TI  - Re-attendance at biennial screening mammography following a repeated false
      positive recall.
AB  - We determined the re-attendance rate at screening mammography after a single or a
      repeated false positive recall and we assessed the effects of transition from
      screen-film mammography (SFM) to full-field digital mammography (FFDM) on
      screening outcome in women recalled twice for the same mammographic abnormality.
      The study population consisted of a consecutive series of 302,912 SFM and 90,288
      FFDM screens. During a 2 years follow-up period (until the next biennial screen),
      we collected the breast imaging reports and biopsy results of all recalled women.
      Re-attendance at biennial screening mammography was 93.2 % (95 % CI 93.1-93.3 %)
      for women with a negative screen (i.e., no recall at screening mammography), 65.4
      % (95 % CI 64.0-66.8 %) for women recalled once, 56.7 % (95 % CI 47.1-66.4 %) for
      women recalled twice but for different lesions and 44.3 % (95 % CI 31.4-57.1 %)
      for women recalled twice for the same lesion. FFDM recalls comprised a
      significantly larger proportion of women who had been recalled twice for the same
      lesion (1.9 % of recalls (52 women) at FFDM vs. 0.9 % of recalls (37 women) at
      SFM, P < 0.001) and the positive predictive value of these recalls (PPV) was
      significantly lower at FFDM (15.4 vs. 35.1 %, P = 0.03). At review, 20 of 52
      women (39.5 %, all with benign outcome) would not have been recalled for a second
      time at FFDM if the previous hard copy SFM screen had been available for
      comparison. We conclude that a repeated false positive recall for the same lesion
      significantly lowered the probability of screening re-attendance. The first round
      of FFDM significantly increased the proportion of women recalled twice for the
      same lesion, with a significantly lower PPV of these lesions. Almost 40 % of
      repeatedly recalled women would not have been recalled the second time if the
      previous hard copy SFM screen had been available for comparison at the time of
      FFDM. 

PMID- 24748570
TI  - Use of menopausal hormone therapy and risk of ductal and lobular breast cancer
      among women 55-74 years of age.
AB  - The Women's Health Initiative (WHI) randomized trials found that use of combined
      estrogen and progestin menopausal hormone therapy (CHT) increases breast cancer
      risk, but use of unopposed estrogen hormone therapy (EHT) does not. However,
      several questions regarding the impact of hormone use on risk of different types
      of breast cancer and what thresholds of use confer elevations in risk remain. We
      conducted a population-based case-control study among women 55-74 years of age to
      assess the association between menopausal hormone use and risk of invasive ductal
      and invasive lobular breast carcinomas. Associations were evaluated using
      polytomous logistic regression and analyses included 880 ductal cases, 1,027
      lobular cases, and 856 controls. Current EHT and CHT use were associated with 1.6
      fold [95 % confidence interval (CI): 1.1-2.2] and 2.3-fold (95 % CI: 1.7-3.2)
      increased risks of lobular breast cancer, respectively, but neither was
      associated with risk of ductal cancer. Lobular cancer risk was increased after 9
      years of EHT use, but after only 3 years of CHT use. Evidence across more than a
      dozen studies indicates that lobular carcinoma is the type of breast cancer most
      strongly influenced by menopausal hormones. Here, we characterize what thresholds
      of duration of use of both EHT and CHT that confer elevations in risk. Despite
      the rapid decline in hormone therapy use the WHI results were published, study of
      the hazards associated with these medications remains relevant given the
      estimated 38 million hormone therapy prescriptions that are still filled in the
      United States annually. 

PMID- 24748571
TI  - Calcium supplements and serum cholesterol.

PMID- 24748572
TI  - Calcium supplements and serum cholesterol. Reply to S I Barr.

PMID- 24748573
TI  - Association between plasma phospholipids and insulin-related variables with
      special reference to statistical validity.

PMID- 24748578
TI  - Fracture in a middle-aged man: uncovering the inside story.

PMID- 24748579
TI  - Plasma free 25-hydroxyvitamin D, vitamin D binding protein, and risk of breast
      cancer in the Nurses' Health Study II.
AB  - PURPOSE: Prior prospective studies, including our own, have evaluated total
      plasma 25-hydroxyvitamin D [25(OH)D] and breast cancer risk with inconsistent
      results. However, recent studies suggest that some vitamin D functions may be
      more relevant to the unbound (free) fraction of 25(OH)D. Vitamin D binding
      protein (DBP) influences the free 25(OH)D levels and thus possibly the biological
      activities of vitamin D. METHODS: We conducted a case-control study nested within
      the Nurses' Health Study II to evaluate the association of plasma free 25(OH)D
      and DBP with breast cancer risk in predominantly premenopausal women. Plasma
      samples were assayed for 25(OH)D and DBP in 584 case-control pairs. Free 25(OH)D
      levels were calculated based on plasma levels of total 25(OH)D, DBP, and a
      constant value representing average albumin levels. Conditional logistic
      regression was used to estimate relative risks (RRs) and 95% confidence intervals
      (CIs). RESULTS: We found no association between plasma calculated free 25(OH)D
      and risk of breast cancer overall (highest vs. lowest quartile RR 1.21, 95% CI
      0.83-1.77, trend test p value = 0.50). No association was observed for plasma DBP
      as well (highest vs. lowest quartile RR 0.95, 95% CI 0.67-1.36, trend test p
      value = 0.96). Results were similar by tumor hormone receptor status. Neither the
      total nor the calculated free 25(OH)D and breast cancer association substantially
      varied by plasma DBP levels. CONCLUSIONS: Our study does not support an important
      role of either calculated circulating free 25(OH)D or circulating DBP levels in
      breast cancer risk among predominantly premenopausal women.

PMID- 24748580
TI  - Mitomycin-based hepatic arterial infusion chemotherapy for solitary ampullary
      cancer liver metastasis: an unusual treatment for an uncommon disease.
AB  - Ampullary carcinoma is an uncommon gastrointestinal disease. Its natural history
      is often characterized by the occurrence of liver metastases. Among patients who
      undergo pancreatoduodenectomy, those presenting with lymph nodes involvement are
      more prone to early distant disease relapse. In this report, a patient previously
      diagnosed with ampullary carcinoma had been treated with curative surgery. After
      subsequent adjuvant gemcitabine, the patient developed significant myelotoxicity
      and suffered from a single liver metastasis a few months later. A hepatic intra
      arterial mitomycin plus fluorouracil-based chemotherapy was administered in order
      to avoid any serious systemic toxicity. The treatment was well tolerated and no
      serious side effects occurred. Extra-hepatic cancer relapse, involving intra
      thoracic and abdominal lymph nodes, was observed not long after the initial intra
      hepatic almost complete response. In conclusion, the locoregional chemotherapy
      administration was effective in overcoming any systemic toxicities and showed
      activity against the liver metastasis but it did not prevent extra-hepatic cancer
      dissemination.

PMID- 24748581
TI  - Carfilzomib-related acute kidney injury may be prevented by N-acetyl-L-cysteine.
AB  - Carfilzomib is a second-generation epoxyketone proteasome inhibitor that is
      approved for treatment of relapsed and refractory multiple myeloma. Phase 2
      trials have reported that 25% of treated patients have renal adverse effects. Pre
      renal/vasoconstriction-related insult from this chemotherapy agent has been
      documented. We describe a case of a 78-year-old man with refractory multiple
      myeloma with acute kidney injury associated with carfilzomib treatment. We show
      that use of N-acetyl-l-cysteine in our patient partially mitigated the renal
      injury upon re-challenge. This case report hypothesizes that acute renal injury
      from carfilzomib is caused by vasoconstriction of the renal vessels, which may be
      prevented by N-acetyl-l-cysteine. 

PMID- 24748582
TI  - Practical considerations in the use of intravenous tacrolimus in hematopoietic
      stem cell transplantation patients.

PMID- 24748583
TI  - Impact of strut-vessel distance and underlying plaque type on the resolution of
      acute strut malapposition: serial optimal coherence tomography analysis after
      everolimus-eluting stent implantation.
AB  - The consequences of acute strut malapposition in everolimus-eluting stents (EES)
      are unknown. This study investigated the impact of strut-vessel (S-V) distance
      and plaque type underneath acute strut malapposition on the mid-term vessel
      response in EES. Twenty-nine patients (35 EES) underwent optical coherence
      tomography (OCT) immediately after percutaneous coronary intervention and at 8
      month follow-up. S-V distance and plaque type (lipid, calcified, or fibrous)
      underneath acute strut malapposition were evaluated. Follow-up OCT classified
      acute strut malapposition as persistent or resolved. The S-V cutoff value for
      predicting resolved strut malapposition and the incidence of intra-stent thrombi
      were determined. Among 569 cases of acute strut malapposition, involving 29,168
      struts, 139 (24.4 %) were persistent. Mean S-V distance was significantly longer
      in persistent than in resolved strut malapposition (600 +/- 294 vs. 231 +/- 95
      MUm; P < 0.0001). S-V distance <=380 MUm was the best cutoff value for predicting
      resolved strut malapposition (sensitivity 93.5 %, specificity 69.8 %, area under
      curve 0.878). Acute strut malapposition with S-V distance <=380 MUm remained
      persistent more frequently over lipid/calcified than over fibrous plaques (lipid:
      13.4 %, calcified: 18.2 %, fibrous: 4.2 %; lipid vs. fibrous, P = 0.001;
      calcified vs. fibrous, P = 0.02). Intra-stent thrombi were more frequent in
      stents with >=1 persistent strut malapposition than in those without [4/11 stents
      (36.3 %) vs. 0/24 (0 %); P = 0.006]. Lipid and calcified plaque, together with S
      V distance, affect the resolution of acute strut malapposition in EES. Persistent
      strut malapposition is associated with the presence of thrombi at follow-up,
      which could be the substrate for late stent thrombosis.

PMID- 24748584
TI  - 'Coronary wrap': IgG4 related disease of coronary artery presenting as a mass
      lesion.

PMID- 24748585
TI  - Mechanical mitral valve thrombosis in an elderly patient.
AB  - Prosthetic valve thrombosis is a rare but dreaded complication of mechanical
      heart valves. In this clinical picture, we present an elderly female who
      developed mechanical mitral valve thrombosis several years after mitral valve
      replacement. We have provided fluoroscopy as well as intraoperative images of
      mitral valve thrombosis and have briefly discussed the diagnosis, and management
      of this complication. 

PMID- 24748586
TI  - Spinal Accessory Nerve Monitoring and Clinical Outcome Results of Nerve-Sparing
      Neck Dissections.
AB  - OBJECTIVE: To investigate the role of intraoperative spinal accessory nerve
      monitoring in predicting postoperative shoulder function in spinal accessory
      nerve-sparing neck dissections. STUDY DESIGN: Prospective, double-blind clinical
      trial. SETTING: Academic, tertiary care center. SUBJECTS AND METHODS: This study
      was performed on 20 neck sites of 17 consecutive patients who had neck
      dissections sparing the spinal accessory nerve. Threshold increment >=0.25 mA and
      amplitude decrement >=72% were classified as significant intraoperative
      neuromonitoring changes while lesser differences were classified as insignificant
      intraoperative neuromonitoring changes. All patients had intraoperative
      neuromonitoring recordings when the spinal accessory nerve was first identified
      and at the end of surgery. Postoperative shoulder function was evaluated
      neurophysiologically with electromyography and clinically with Constant-Murley
      Score; daily activity restrictions were evaluated with Activity Restriction
      Scale. RESULTS: Clinical assessment of shoulder functions at postoperative first
      and second months showed statistically significant deteriorations when compared
      with preoperative values (P < .05). The shoulder function deterioration was
      statistically significantly less for patients with insignificant intraoperative
      neuromonitoring changes than patients with significant intraoperative
      neuromonitoring changes (P < .05). Daily activity restriction deteriorations were
      present in both groups at first postoperative month (P < .05). While they
      persisted in the group with significant intraoperative neuromonitoring changes
      during the second postoperative month (P < .05), there was continuing recovery in
      the insignificant intraoperative neuromonitoring change group and statistical
      significance disappeared (P > .05). CONCLUSION: Our results support the
      predictive value of spinal accessory nerve intraoperative neuromonitoring for
      determining shoulder function deterioration and activity restriction scores.

PMID- 24748587
TI  - Caregiver Quality of Life Is Related to Severity of Otitis Media in Children.
AB  - OBJECTIVE: Otitis media (OM) in children is the most frequent reason for
      physician visits in developed countries and burdens caregivers, society, and the
      child. Our objective was to describe the impact of OM severity on
      parent/caregiver quality of life (QoL). STUDY DESIGN: Multi-institutional
      prospective cross-sectional study. SETTING: Otolaryngology, family, and pediatric
      practices. SUBJECTS AND METHODS: Children 6 to 24 months old with and without a
      primary diagnosis of recurrent OM and their caregivers. Physicians provided
      patient history, and parents/caregivers completed a Family Information Form, the
      PedsQL Family Impact survey, the Patient Reported Outcomes Measurement
      Information System (PROMIS) survey, and the OM 6-item severity survey (OM-6).
      RESULTS: A total of 2413 subjects were enrolled and data from 1208 patients and
      physician were analyzed. The average child age was 16 months, and 54% were male.
      The mean OM-6 score was 3.2. The mean PedsQL Family Impact score for parents was
      66.9 from otolaryngology sites and 78.8 from pediatrics/family practice sites (P
      < .001). Higher (worse) OM-6 scores correlated significantly with worse PedsQL
      Family Impact scores (Pearson r = -0.512, P < .01). Similarly, increasing OM-6
      scores strongly correlated with increased parental anxiety, depression, and
      fatigue, as well as decreased satisfaction (all P < .01). CONCLUSIONS: Worse
      PedsQL Family Impact and PROMIS scores were highly correlated with elevated OM-6
      scores, suggesting that severity of childhood OM significantly affects
      parent/caregiver QoL. Understanding the impact of a child's illness on
      parent/caregiver QoL can help physicians counsel patients and families and
      provide better family-centered, compassionate care.

PMID- 24748588
TI  - Cochrane Corner: Amplification with Hearing Aids for Patients with Tinnitus and
      Co-existing Hearing Loss.
AB  - The "Cochrane Corner" is a section in the journal that highlights systematic
      reviews relevant to otolaryngology-head and neck surgery, with invited commentary
      to aid clinical decision making. This installment features a Cochrane review,
      "Amplification with Hearing Aids for Patients with Tinnitus and Co-existing
      Hearing Loss," which identified only 1 randomized controlled trial and concluded
      that current evidence for use of hearing aids is limited.

PMID- 24748589
TI  - Pattern of Failure in Surgically Treated Patients with Cervical Esophageal
      Squamous Cell Carcinoma.
AB  - OBJECTIVE: The aim of this study was to analyze the pattern of failure in
      patients who have undergone surgical resection for cervical esophageal squamous
      cell carcinoma. STUDY DESIGN: Case series with chart review. SETTING: University
      hospital. SUBJECTS AND METHODS: Sixty-two patients who had undergone surgical
      resection of cervical esophageal squamous cell carcinoma from January 2001
      through April 2012. Sites of failure were documented. RESULTS: Twenty-nine
      patients had developed treatment failure. Of the 29 patients, 14, 13, and 14 had
      developed local failure, regional failure, and distant metastasis, respectively.
      Of the 13 regional failures, the images of 2 patients were lost. The other 11
      regional failures included left lateral nodal disease at level II (n = 2), level
      III (n = 4), and level IV (n = 7); right lateral nodal disease at level II (n =
      2), level III (n = 3), and level IV (n = 3); and level VI (n = 4). The overall 2
      year local failure-free survival rate and regional failure-free survival rates
      were 79.6% and 58.6% (P = .04) for patients with stage II disease and 79.6% and
      59.6% (P = .054) for patients with stage III disease, respectively. CONCLUSIONS:
      The pattern of failure of cervical esophageal squamous cell carcinoma is
      characterized by early locoregional failure, especially in patients with stage
      III disease.

PMID- 24748590
TI  - A-769662 potentiates the effect of other AMP-activated protein kinase activators
      on cardiac glucose uptake.
AB  - AMP-activated protein kinase (AMPK), a key cellular sensor of energy, regulates
      metabolic homeostasis and plays a protective role in the ischemic or diabetic
      heart. Stimulation of cardiac glucose uptake contributes to this AMPK-mediated
      protection. The small-molecule AMPK activator A-769662, which binds and directly
      activates AMPK, has recently been characterized. A-769662-dependent AMPK
      activation protects the heart against an ischemia-reperfusion episode but is
      unable to stimulate skeletal muscle glucose uptake. Here, we tried to reconcile
      these conflicting findings by investigating the impact of A-769662 on cardiac
      AMPK signaling and glucose uptake. We showed that A-769662 promoted AMPK
      activation, resulting in the phosphorylation of several downstream targets, but
      was incapable of stimulating glucose uptake in cultured cardiomyocytes and the
      perfused heart. The lack of glucose uptake stimulation can be explained by A
      769662's narrow specificity, since it selectively activates cardiac AMPK
      heterotrimeric complexes containing alpha2/beta1-subunits, the others being
      presumably required for this metabolic outcome. However, when combined with
      classical AMPK activators, such as metformin, phenformin, oligomycin, or hypoxia,
      which impact AMPK heterotrimers more broadly via elevation of cellular AMP
      levels, A-769662 induced more profound AMPK phosphorylation and subsequent
      glucose uptake stimulation. The synergistic effect of A-769662 under such
      ischemia-mimetic conditions protected cardiomyocytes against ROS production and
      cell death. In conclusion, despite the fact that A-769662 activates AMPK, it
      alone does not significantly stimulate glucose uptake. However, strikingly, its
      ability of potentiating the action on other AMPK activators makes it a
      potentially useful participant in the protective role of AMPK in the heart.

PMID- 24748591
TI  - Mechano-electrical coupling as framework for understanding functional remodeling
      during LBBB and CRT.
AB  - It is not understood why, after onset of left bundle-branch block (LBBB), acute
      worsening of cardiac function is followed by a further gradual deterioration of
      function, whereas most adverse cardiac events lead to compensatory adaptations.
      We investigated whether mechano-electrical coupling (MEC) can explain long-term
      remodeling with LBBB and cardiac resynchronization therapy (CRT). To this
      purpose, we used an integrative modeling approach relating local ventricular
      electrophysiology, calcium handling, and excitation-contraction coupling to
      global cardiovascular mechanics and hemodynamics. Each ventricular wall was
      composed of multiple mechanically and electrically coupled myocardial segments.
      MEC was incorporated by allowing adaptation of L-type Ca(2+) current aiming at
      minimal dispersion of local external work, an approach that we previously applied
      to replicate T-wave memory in a synchronous heart after a period of asynchronous
      activation. LBBB instantaneously decreased left-ventricular stroke work and
      increased end-diastolic volume. During sustained LBBB, MEC reduced
      intraventricular dispersion of mechanical workload and repolarization. However,
      MEC-induced reduction in contractility in late-activated regions was larger than
      the contractility increase in early-activated regions, resulting in further
      decrease of stroke work and increase of end-diastolic volume. Upon the start of
      CRT, stroke work increased despite a wider dispersion of mechanical workload.
      During sustained CRT, MEC-induced reduction in dispersion of workload and
      repolarization coincided with a further reduction in end-diastolic volume. In
      conclusion, MEC may represent a useful framework for better understanding the
      long-term changes in cardiac electrophysiology and contraction following LBBB as
      well as CRT.

PMID- 24748592
TI  - Reduction of Na/K-ATPase affects cardiac remodeling and increases c-kit cell
      abundance in partial nephrectomized mice.
AB  - The current study examined the role of Na/K-ATPase alpha1-subunit in animals
      subjected to 5/6th partial nephrectomy (PNx) using Na/K-ATPase alpha1
      heterozygous (alpha1(+/-)) mice and their wild-type (WT) littermates. After PNx,
      both WT and alpha1(+/-) animals displayed diastolic dimension increases,
      increased blood pressure, and increased cardiac hypertrophy. However, in the
      alpha1(+/-) animals we detected significant increases in cardiac cell death in
      PNx animals. Given that reduction of alpha1 elicited increased cardiac cell death
      with PNx, while at the same time these animals developed cardiac hypertrophy, an
      examination of cardiac cell number, and proliferative capabilities of those cells
      was carried out. Cardiac tissues were probed for the progenitor cell marker c-kit
      and the proliferation marker ki-67. The results revealed that alpha1(+/-) mice
      had significantly higher numbers of c-kit-positive and ki-67-positive cells,
      especially in the PNx group. We also found that alpha1(+/-) mice express higher
      levels of stem cell factor, a c-kit ligand, in their heart tissue and had higher
      circulating levels of stem cell factor than WT animals. In addition, PNx induced
      significant enlargement of cardiac myocytes in WT mice but has much less effect
      in alpha1(+/-) mice. However, the total cell number determined by nuclear
      counting is higher in alpha1(+/-) mice with PNx compared with WT mice. We
      conclude that PNx induces hypertrophic growth and high blood pressure regardless
      of Na/K-ATPase content change. However, total cardiac cell number as well as c
      kit-positive cell number is increased in alpha1(+/-) mice with PNx.

PMID- 24748593
TI  - The presence of the NOS3 gene polymorphism for intron 4 mitigates the beneficial
      effects of exercise training on ambulatory blood pressure monitoring in adults.
AB  - The number of studies that have evaluated exercise training (ET) and nitric oxide
      synthase (NOS)3 gene polymorphisms is scarce. The present study was designed to
      evaluate the relationship between exercise training and NOS3 polymorphisms at 
      786T>C, 894G>T, and intron 4b/a on blood pressure (BP) using 24-h ambulatory BP
      monitoring (ABPM), nitrate/nitrite levels (NOx), and redox state. Eighty-six
      volunteers (51 +/- 0.6 yr old) were genotyped into nonpolymorphic and polymorphic
      groups for each of the three positions of NOS3 polymorphisms. Auscultatory BP,
      ABPM, SOD activity, catalase activity, NOx levels, and malondialdehyde levels
      were measured. DNA was extracted from leukocytes, and PCR followed by sequencing
      was applied for genotype analysis. Aerobic ET consisted of 24 sessions for 3
      days/wk for 40 min at moderate intensity. This study was performed in a double
      blind and crossover format. ET was effective in lowering office BP (systolic BP:
      3.2% and diastolic BP: 3%) as well as ABPM (systolic BP: 2% and diastolic BP:
      1.3%). Increased SOD and catalase activity (42.6% and 15.1%, respectively) were
      also observed. The NOS3 polymorphism for intron 4 mitigated the beneficial effect
      of ET for systolic BP (nonpolymorphic group: -3.0% and polymorphic group: -0.6%)
      and diastolic BP (nonpolymorphic group: -3.2% and polymorphic group: -0.5%), but
      it was not associated with NOx level and redox state. Paradoxical responses were
      found for positions T786-C and G894T for the NOS3 gene. Consistently, the
      presence of the polymorphism for intron 4 blunted the beneficial effects of ET in
      middle-aged adults. Possibly, this effect might be as consequence of intron 4
      acting as a short intronic repeat RNA controlling endothelial NOS activity
      epigenetically. 

PMID- 24748594
TI  - SIRT3 deficiency exacerbates ischemia-reperfusion injury: implication for aged
      hearts.
AB  - Ischemia-reperfusion (IR) injury is significantly worse in aged hearts, but the
      underlying mechanisms are poorly understood. Age-related damage to mitochondria
      may be a critical feature, which manifests in an exacerbation of IR injury.
      Silent information regulator of transcription 3 (SIRT3), the major mitochondrial
      NAD(+)-dependent lysine deacetylase, regulates a variety of functions, and its
      inhibition may disrupt mitochondrial function to impact recovery from IR injury.
      In this study, the role of SIRT3 in mediating the response to cardiac IR injury
      was examined using an in vitro model of SIRT3 knockdown (SIRT3(kd)) in H9c2
      cardiac-derived cells and in Langendorff preparations from adult (7 mo old) wild
      type (WT) and SIRT3(+/-) hearts and aged (18 mo old) WT hearts. SIRT3(kd) cells
      were more vulnerable to simulated IR injury and exhibited a 46% decrease in
      mitochondrial complex I (Cx I) activity with low O2 consumption rates compared
      with controls. In the Langendorff model, SIRT3(+/-) adult hearts showed less
      functional recovery and greater infarct vs. WT, which recapitulates the in vitro
      results. In WT aged hearts, recovery from IR injury was similar to SIRT3(+/-)
      adult hearts. Mitochondrial protein acetylation was increased in both SIRT3(+/-)
      adult and WT aged hearts (relative to WT adult), suggesting similar activities of
      SIRT3. Also, enzymatic activities of two SIRT3 targets, Cx I and MnSOD, were
      similarly and significantly inhibited in SIRT3(+/-) adult and WT aged cardiac
      mitochondria. In conclusion, decreased SIRT3 may increase the susceptibility of
      cardiac-derived cells and adult hearts to IR injury and may contribute to a
      greater level of IR injury in the aged heart.

PMID- 24748597
TI  - Implementing the PEP uP Protocol in Critical Care Units in Canada: Results of a
      Multicenter, Quality Improvement Study.
AB  - BACKGROUND: Previous studies have documented widespread iatrogenic underfeeding
      in intensive care unit (ICU) patients. In an experimental setting, we
      demonstrated the safety and efficacy of a novel enteral feeding protocol designed
      to overcome the main barriers to adequate delivery of enteral nutrition (EN), the
      Enhanced Protein-Energy Provision via the Enteral Route Feeding Protocol (PEP uP
      protocol). The purpose of this article is to describe our experience with
      implementing this feeding protocol under "real-world" settings in Canada.
      MATERIALS AND METHODS: This study is a multicenter quality improvement initiative
      with a concurrent control group. Selected ICUs implemented the PEP uP protocol,
      and nutrition practices and outcomes were compared with a concurrent control
      group of ICUs. RESULTS: In 2013, of the 24 ICUs from Canada that participated in
      the International Nutrition Survey, 8 implemented the PEP uP protocol and the
      remaining 16 served as concurrent control sites. Patients at PEP uP sites
      received 60.1% of their prescribed energy requirements from EN compared with
      49.9% in patients from control hospitals (P = .02). In addition, patients in PEP
      uP protocol sites received more protein from EN (61.0% vs 49.7% of prescribed
      amounts; P = .01), were more likely to receive protein supplements (71.8% vs
      47.7%; P = .01), and were more likely to receive >80% of their protein
      requirements by day 3 (46.1% vs 29.3%; P = .05) compared with patients in control
      hospitals. CONCLUSIONS: In the real-life setting, the PEP uP protocol can improve
      the delivery of EN to critically ill patients.

PMID- 24748598
TI  - Use of 3 tools to assess nutrition risk in the intensive care unit.
AB  - BACKGROUND: Identifying patients at nutrition risk proves difficult in the
      intensive care unit (ICU) due to the nature of critical illness. No consensus
      exists on the most appropriate method to identify these patients. Traditional
      screens and assessments are often limited due to their subjective nature. The
      purpose of the quality improvement project was to compare proportions of ICU
      patients deemed at nutrition risk using 3 different tools. MATERIAL AND METHODS:
      A convenience sample of 294 patients admitted to the ICU was used. Patients were
      assessed using the institution's routine nutrition screening method, the
      Subjective Global Assessment (SGA), and the NUTrition Risk in Critically ill
      (NUTRIC) score. Information was collected on demographics, severity of illness,
      hospital and ICU length of stay (LOS), and disposition. Descriptive statistics
      were used to examine counts/proportions of risk categories; means +/- SD were
      used to summarize demographic and clinical variables. RESULTS: A total of 139
      patients (47%) were deemed at nutrition risk or malnourished by at least 1 tool.
      Patients identified were older and had a lower body mass index, more weight loss,
      more fat and muscle wasting, more fluid accumulation, and lower average handgrips
      than those not at nutrition risk; they also had longer hospital and ICU LOS,
      higher rates of requiring further rehabilitation upon discharge, and higher
      mortality during hospitalization. CONCLUSION: Traditional screening and
      assessment tools did not uniformly identify patients as malnourished or at
      nutrition risk in the ICU and therefore may be inappropriate for use in this
      population. Inclusion of physical assessment, functional status, and severity of
      illness may be useful in predicting nutrition risk in the ICU.

PMID- 24748599
TI  - Evidence of local adaptation in plant virus effects on host-vector interactions.
AB  - Recent research suggests that plant viruses, and other pathogens, frequently
      alter host-plant phenotypes in ways that facilitate transmission by arthropod
      vectors. However, many viruses infect multiple hosts, raising questions about
      whether these pathogens are capable of inducing transmission-facilitating
      phenotypes in phylogenetically divergent host plants and the extent to which
      evolutionary history with a given host or plant community influences such
      effects. To explore these issues, we worked with two newly acquired field
      isolates of cucumber mosaic virus (CMV)-a widespread multi-host plant pathogen
      transmitted in a non-persistent manner by aphids-and explored effects on the
      phenotypes of different host plants and on their subsequent interactions with
      aphid vectors. An isolate collected from cultivated squash fields (KVPG2-CMV)
      induced in the native squash host (Cucurbita pepo) a suite of effects on host
      vector interactions suggested by previous work to be conducive to transmission
      (including reduced host-plant quality for aphids, rapid aphid dispersal from
      infected to healthy plants, and enhanced aphid attraction to the elevated
      emission of a volatile blend similar to that of healthy plants). A second isolate
      (P1-CMV) collected from cultivated pepper (Capsicum annuum) induced more neutral
      effects in its native host (largely exhibiting non-significant trends in the
      direction of effects seen for KVPG2-CMV in squash). When we attempted cross-host
      inoculations of these two CMV isolates (KVPG2-CMV in pepper and P1-CMV in
      squash), P1-CMV was only sporadically able to infect the novel host; KVPG2-CMV
      infected the novel pepper host with somewhat reduced success compared with its
      native host and reached virus titers significantly lower than those observed for
      either strain in its native host. Furthermore, KVPG2-CMV induced changes in the
      phenotype of the novel host, and consequently in host-vector interactions,
      dramatically different than those observed in the native host and apparently
      maladaptive with respect to virus transmission (e.g., host plant quality for
      aphids was significantly improved in this instance, and aphid dispersal was
      reduced). Taken together, these findings provide evidence of adaption by CMV to
      local hosts (including reduced infectivity and replication in novel versus native
      hosts) and further suggest that such adaptation may extend to effects on host
      plant traits mediating interactions with aphid vectors. Thus, these results are
      consistent with the hypothesis that virus effects on host-vector interactions can
      be adaptive, and they suggest that multi-host pathogens may exhibit adaptation
      with respect to these and other effects on host phenotypes, perhaps especially in
      homogeneous monocultures. 

PMID- 24748600
TI  - Developmental change in the function of movement systems: transition of the
      pectoral fins between respiratory and locomotor roles in zebrafish.
AB  - An animal may experience strikingly different functional demands on its body's
      systems through development. One way of meeting those demands is with temporary,
      stage-specific adaptations. This strategy requires the animal to develop
      appropriate morphological states or physiological pathways that address transient
      functional demands as well as processes that transition morphology, physiology,
      and function to that of the mature form. Recent research on ray-finned
      (actinopterygian) fishes is a developmental transition in function of the
      pectoral fin, thereby providing an opportunity to examine how an organism copes
      with changes in the roles of its morphology between stages of its life history.
      As larvae, zebrafish alternate their pectoral fins in coordination with the body
      axis during slow swimming. The movements of their fins do not appear to
      contribute to the production of thrust or to stability but instead exchange fluid
      near the body for cutaneous respiration. The morphology of the larval fin
      includes a simple stage-specific endoskeletal disc overlaid by fan-shaped
      adductor and abductor muscles. In contrast, the musculoskeletal system of the
      mature fin consists of a suite of muscles and bones. Fins are extended laterally
      during slow swimming of the adult, without the distinct, high-amplitude left
      right fin alternation of the larval fin. The morphological and functional
      transition of the pectoral fin occurs through juvenile development. Early in this
      period, at about 3 weeks post-fertilization, the gills take over respiratory
      function, presumably freeing the fins for other roles. Kinematic data suggest
      that the loss of respiratory function does not lead to a rapid switch in patterns
      of fin movement but rather that both morphology and movement transition gradually
      through the juvenile stage of development. Studies relating structure to function
      often focus on stable systems that are arguably well adapted for the roles they
      play. Examining how animals navigate transitional periods, when the link of
      structure to function may be less taut, provides insight both into how animals
      contend with such change and into the developmental pressures that shape mature
      form and function. 

PMID- 24748601
TI  - Mitochondria in lung biology and pathology: more than just a powerhouse.
AB  - An explosion of new information about mitochondria reveals that their importance
      extends well beyond their time-honored function as the "powerhouse of the cell."
      In this Perspectives article, we summarize new evidence showing that mitochondria
      are at the center of a reactive oxygen species (ROS)-dependent pathway governing
      the response to hypoxia and to mitochondrial quality control. The potential role
      of the mitochondrial genome as a sentinel molecule governing cytotoxic responses
      of lung cells to ROS stress also is highlighted. Additional attention is devoted
      to the fate of damaged mitochondrial DNA relative to its involvement as a damage
      associated molecular pattern driving adverse lung and systemic cell responses in
      severe illness or trauma. Finally, emerging strategies for replenishing normal
      populations of mitochondria after damage, either through promotion of
      mitochondrial biogenesis or via mitochondrial transfer, are discussed. 

PMID- 24748602
TI  - Lung fibroblasts accelerate wound closure in human alveolar epithelial cells
      through hepatocyte growth factor/c-Met signaling.
AB  - There are 190,600 cases of acute lung injury/acute respiratory distress syndrome
      (ALI/ARDS) each year in the United States, and the incidence and mortality of
      ALI/ARDS increase dramatically with age. Patients with ALI/ARDS have alveolar
      epithelial injury, which may be worsened by high-pressure mechanical ventilation.
      Alveolar type II (ATII) cells are the progenitor cells for the alveolar
      epithelium and are required to reestablish the alveolar epithelium during the
      recovery process from ALI/ARDS. Lung fibroblasts (FBs) migrate and proliferate
      early after lung injury and likely are an important source of growth factors for
      epithelial repair. However, how lung FBs affect epithelial wound healing in the
      human adult lung has not been investigated in detail. Hepatocyte growth factor
      (HGF) is known to be released mainly from FBs and to stimulate both migration and
      proliferation of primary rat ATII cells. HGF is also increased in lung tissue,
      bronchoalveolar lavage fluid, and serum in patients with ALI/ARDS. Therefore, we
      hypothesized that HGF secreted by FBs would enhance wound closure in alveolar
      epithelial cells (AECs). Wound closure was measured using a scratch wound-healing
      assay in primary human AEC monolayers and in a coculture system with FBs. We
      found that wound closure was accelerated by FBs mainly through HGF/c-Met
      signaling. HGF also restored impaired wound healing in AECs from the elderly
      subjects and after exposure to cyclic stretch. We conclude that HGF is the
      critical factor released from FBs to close wounds in human AEC monolayers and
      suggest that HGF is a potential strategy for hastening alveolar repair in
      patients with ALI/ARDS. 

PMID- 24748603
TI  - Sustained hyperoxia-induced NF-kappaB activation improves survival and preserves
      lung development in neonatal mice.
AB  - Oxygen toxicity contributes to the pathogenesis of bronchopulmonary dysplasia
      (BPD). Neonatal mice exposed to hyperoxia develop a simplified lung structure
      that resembles BPD. Sustained activation of the transcription factor NF-kappaB
      and increased expression of protective target genes attenuate hyperoxia-induced
      mortality in adults. However, the effect of enhancing hyperoxia-induced NF-kappaB
      activity on lung injury and development in neonatal animals is unknown. We
      performed this study to determine whether sustained NF-kappaB activation,
      mediated through IkappaBbeta overexpression, preserves lung development in
      neonatal animals exposed to hyperoxia. Newborn wild-type (WT) and IkappaBbeta
      overexpressing (AKBI) mice were exposed to hyperoxia (>95%) or room air from day
      of life (DOL) 0-14, after which all animals were kept in room air. Survival
      curves were generated through DOL 14. Lung development was assessed using radial
      alveolar count (RAC) and mean linear intercept (MLI) at DOL 3 and 28 and
      pulmonary vessel density at DOL 28. Lung tissue was collected, and NF-kappaB
      activity was assessed using Western blot for IkappaB degradation and NF-kappaB
      nuclear translocation. WT mice demonstrated 80% mortality through 14 days of
      exposure. In contrast, AKBI mice demonstrated 60% survival. Decreased RAC,
      increased MLI, and pulmonary vessel density caused by hyperoxia in WT mice were
      significantly attenuated in AKBI mice. These findings were associated with early
      and sustained NF-kappaB activation and expression of cytoprotective target genes,
      including vascular endothelial growth factor receptor 2. We conclude that
      sustained hyperoxia-induced NF-kappaB activation improves neonatal survival and
      preserves lung development. Potentiating early NF-kappaB activity after hyperoxic
      exposure may represent a therapeutic intervention to prevent BPD.

PMID- 24748604
TI  - Bronchial epithelial injury in the context of alloimmunity promotes lymphocytic
      bronchiolitis through hyaluronan expression.
AB  - Epithelial injury is often detected in lung allografts, however, its relation to
      rejection pathogenesis is unknown. We hypothesized that sterile epithelial injury
      can lead to alloimmune activation in the lung. We performed adoptive transfer of
      mismatched splenocytes into recombinant activating gene 1 (Rag1)-deficient mice
      to induce an alloimmune status and then exposed these mice to naphthalene to
      induce sterile epithelial injury. We evaluated lungs for presence of alloimmune
      lung injury, endoplasmic reticulum (ER) stress, and hyaluronan expression,
      examined the effect of ER stress induction on hyaluronan expression and
      lymphocyte trapping by bronchial epithelia in vitro, and examined airways from
      patients with bronchiolitis obliterans syndrome and normal controls
      histologically. We found that Rag1-deficient mice that received mismatched
      splenocytes and naphthalene injection displayed bronchial epithelial ER stress,
      peribronchial hyaluronan expression, and lymphocytic bronchitis. Bronchial
      epithelial ER stress led to the expression of lymphocyte-trapping hyaluronan
      cables in vitro. Blockade of hyaluronan binding ameliorated naphthalene-induced
      lymphocytic bronchitis. ER stress was present histologically in >40% of bronchial
      epithelia of BOS patients and associated with subepithelial hyaluronan
      deposition. We conclude that sterile bronchial epithelial injury in the context
      of alloimmunity can lead to sustained ER stress and promote allograft rejection
      through hyaluronan expression. 

PMID- 24748605
TI  - Resection of a bronchogenic cyst in the first decade of life with robotic
      surgery.
AB  - The conventional surgical approach for the removal of bronchogenic cyst in
      children is thoracotomy. Video-assisted thoracoscopic surgery is still under
      debate with the concerns of incomplete removal and injury to major intrathoracic
      structures. In this case report, we present an 8-year old patient who was
      successfully treated with robotic surgery (Intuitive Surgical, Mountain View, CA,
      USA). Robotic technology enables precise dissection and complete resection of the
      thoracic bronchogenic cyst without violating the capsule and adjacent major
      intrathoracic structures. She was discharged on postoperative Day 2 and was
      active on Day 5. 

PMID- 24748606
TI  - Simultaneous video-assisted thoracoscopic surgery sleeve lobectomy and
      thymectomy.
AB  - Thymic carcinoid tumour associated with pulmonary squamous cell carcinoma is very
      rare. We present a case of synchronous lung cancer and mediastinal tumour treated
      with simultaneous video-assisted thoracoscopic surgery (VATS) sleeve lobectomy
      and thymectomy. A 67-year old man presented with cough and bloody sputum. Chest
      computed tomography showed an anterior mediastinal mass with a right hilar
      nodule. A right upper sleeve lobectomy and a thymectomy were performed via a VATS
      approach. Thymic carcinoid tumour associated with pulmonary squamous cell
      carcinoma was diagnosed, and the patient received adjuvant radiochemotherapy. 

PMID- 24748607
TI  - Exchanging care records using HL7 V3 care provision messages.
AB  - OBJECTIVE: This paper describes Health Level 7 (HL7) V.3 Care Transfer, Care
      Record Query, and Care Record messages. This is the core of the Care Provision
      Domain in the HL7 standard which became normative at the end of 2012 and is an
      American National Standards Institute (ANSI)-approved HL7 standard. BACKGROUND
      AND SIGNIFICANCE: Using a message is somewhat different from the approach offered
      in the current HL7 Clinical Document Architecture (CDA). The overall advantage is
      human-to-human communication and system-to-system processing of structured data
      through electronic messages, supporting continuity of care and interactive
      structured data exchange through querying. MATERIALS AND METHODS: The Care
      Provision Domain Model in HL7 was developed based on use cases from several
      projects internationally. Use case and information analysis, model building, HL7
      consensus methods (eg, working group meetings), conference calls, balloting, a
      draft standard for trial use, pilot implementations, and subsequent evaluation
      were applied. RESULTS: The membership and pilot implementers gave feedback to
      improve the draft standard. After the formal ballot process, HL7 membership
      accepted it as a normative standard and it is now ANSI approved. The Care
      Provision Domain Model defines the structure (data exchanged) and dynamics
      (workflow and communications) of the Care Record, Care Record Query, and Care
      Transfer. DISCUSSION AND CONCLUSIONS: The HL7 V3 Care Provision Domain differs
      from the HL7 CDA regarding support of the dynamics of care (eg, for continuity of
      care) as provided through a series of interactions and queries, but is similar
      with respect to the data and their organization.

PMID- 24748608
TI  - Is UV-induced DNA damage greater at higher elevation?
AB  - * PREMISE OF THE STUDY: Although ultraviolet radiation (UV) is known to have
      negative effects on plant growth, there has been no direct evidence that plants
      growing at higher elevations are more severely affected by ultraviolet-B (UV-B)
      radiation, which is known to increase with elevation. We examined damage to DNA,
      a primary target of UV-B, in the widespread species Polygonum sachalinense
      (Fallopia sachalinensis) and Plantago asiatica at two elevations.* METHODS: We
      sampled leaves of both species at 300 and 1700 m above sea level every 2 h for 11
      d across the growing season and determined the level of cyclobutane pyrimidine
      dimer (CPD), a major product of UV damage to DNA.* KEY RESULTS: The CPD level was
      significantly influenced by the time of day, date, elevation, and their
      interactions in both species. The CPD level tended to be higher at noon or on
      sunny days. DNA damage was more severe at 1700 m than at 300 m: on average, 8.7%
      greater at high elevation in P. asiatica and 7.8% greater in P. sachalinense
      Stepwise multiple regression analysis indicated that the CPD level was explained
      mainly by UV-B and had no significant relationship with other environmental
      factors such as temperature and photosynthetically active radiation.*
      CONCLUSIONS: UV-induced DNA damage in plants is greater at higher elevations.

PMID- 24748609
TI  - Utilizing syndromic surveillance data for estimating levels of influenza
      circulation.
AB  - The availability of weekly Web-based participatory surveillance data on self
      reported influenza-like illness (ILI), defined here as self-reported fever and
      cough/sore throat, over several influenza seasons allows for estimation of the
      incidence of influenza infection in population cohorts. We demonstrate this using
      syndromic data reported through the Influenzanet surveillance platform in the
      Netherlands. We used the 2011-2012 influenza season, a low-incidence season that
      began late, to assess the baseline rates of self-reported ILI during periods of
      low influenza circulation, and we used ILI rates above that baseline level from
      the 2012-1013 season, a major influenza season, to estimate influenza attack
      rates for that period. The latter conversion required estimates of age-specific
      probabilities of self-reported ILI given influenza (Flu) infection (P(ILI |
      Flu)), which were obtained from separate data (extracted from Hong Kong, China,
      household studies). For the 2012-2013 influenza season in the Netherlands, we
      estimated combined influenza A/B attack rates of 29.2% (95% credible interval
      (CI): 21.6, 37.9) among survey participants aged 20-49 years, 28.3% (95% CI:
      20.7, 36.8) among participants aged 50-60 years, and 5.9% (95% CI: 0.4, 11.8)
      among participants aged >=61 years. Estimates of influenza attack rates can be
      obtained in other settings using analogous, multiseason surveillance data on self
      reported ILI together with separate, context-specific estimates of P(ILI | Flu). 

PMID- 24748610
TI  - Factors predicting rotator cuff retears: an analysis of 1000 consecutive rotator
      cuff repairs.
AB  - BACKGROUND: The rate of retears after rotator cuff repair varies from 11% to 94%.
      A retear is associated with poorer subjective and objective clinical outcomes
      than intact repair. PURPOSE: This study was designed to determine which
      preoperative and/or intraoperative factors held the greatest association with
      retears after arthroscopic rotator cuff repair. STUDY DESIGN: Cohort study; Level
      of evidence, 3. METHODS: This study retrospectively evaluated 1000 consecutive
      patients who had undergone a primary rotator cuff repair by a single surgeon
      using an arthroscopic inverted-mattress knotless technique and who had undergone
      an ultrasound evaluation 6 months after surgery to assess repair integrity.
      Exclusion criteria included previous rotator cuff repair on the same shoulder,
      incomplete repair, and repair using a synthetic polytetrafluoroethylene patch.
      All patients had completed the modified L'Insalata Questionnaire and underwent a
      clinical examination before surgery. Measurements of tear size, tear thickness,
      associated shoulder injury, tissue quality, and tendon mobility were recorded
      intraoperatively. RESULTS: The overall retear rate at 6 months after surgery was
      17%. Retears occurred in 27% of full-thickness tears and 5% of partial-thickness
      tears (P < .0001). The best independent predictors of retears were
      anteroposterior tear length (correlation coefficient r = 0.41, P < .0001), tear
      size area (r = 0.40, P < .0001), mediolateral tear length (r = 0.34, P < .0001),
      tear thickness (r = 0.29, P < .0001), age at surgery (r = 0.27, P < .0001), and
      operative time (r = 0.18, P < .0001). These factors produced a predictive model
      for retears: logit P = (0.039 * age at surgery in years) + (0.027 * tear
      thickness in %) + (1 * anteroposterior tear length in cm) + (0.76 * mediolateral
      tear length in cm) - (0.17 * tear size area in cm(2)) + (0.018 * operative time
      in minutes) -9.7. Logit P can be transformed into P, which is the chance of
      retears at 6 months after surgery. CONCLUSION: A rotator cuff retear is a
      multifactorial process with no single preoperative or intraoperative factor being
      overwhelmingly predictive of it. Nevertheless, rotator cuff tear size (tear
      dimensions, tear size area, and tear thickness) showed stronger associations with
      retears at 6 months after surgery than did measures of tissue quality and
      concomitant shoulder injuries.

PMID- 24748611
TI  - Bony Landmarks of the Anterior Cruciate Ligament Tibial Footprint: A Detailed
      Analysis Comparing 3-Dimensional Computed Tomography Images to Visual and
      Histological Evaluations.
AB  - BACKGROUND: Although the importance of tibial tunnel position for achieving
      stability after anterior cruciate ligament (ACL) reconstruction was recently
      recognized, there are fewer detailed reports of the anatomy of the tibial
      topographic footprint compared with the femoral side. HYPOTHESIS: The ACL tibial
      footprint has a relationship to bony prominences and surrounding bony landmarks.
      STUDY DESIGN: Descriptive laboratory study. METHODS: This study consisted of 2
      anatomic procedures for the identification of bony prominences that correspond to
      the ACL tibial footprint and 3 surrounding landmarks: the anterior ridge, lateral
      groove, and intertubercular fossa. In the first procedure, after computed
      tomography (CT) was performed on 12 paired, embalmed cadaveric knees, 12 knees
      were visually observed, while their contralateral knees were histologically
      observed. Comparisons were made between macroscopic and microscopic findings and
      3-dimensional (3D) CT images of these bony landmarks. In the second procedure,
      the shape of the bony prominence and incidence of their bony landmarks were
      evaluated from the preoperative CT data of 60 knee joints. RESULTS: In the first
      procedure, we were able to confirm a bony prominence and all 3 surrounding
      landmarks by CT in all cases. Visual evaluation confirmed a small bony eminence
      at the anterior boundary of the ACL. The lateral groove was not confirmed
      macroscopically. The ACL was not attached to the lateral intercondylar tubercle,
      ACL tibial ridge, and intertubercular space at the posterior boundary.
      Histological evaluation confirmed that the anterior ridge and lateral groove were
      positioned at the anterior and lateral boundaries, respectively. There was no
      ligament tissue on the intercondylar space corresponding to the intercondylar
      fossa. In the second investigation, the bony prominence showed 2 morphological
      patterns: an oval type (58.3%) and a triangular type (41.6%). The 3 bony
      landmarks, including the anterior ridge, lateral groove, and intertubercular
      fossa, existed in 96.6%, 100.0%, and 96.6% of the cases, respectively.
      CONCLUSION: There is a bony prominence corresponding to the ACL footprint and
      bony landmarks on the anterior, posterior, and lateral boundaries. CLINICAL
      RELEVANCE: The study results may help create an accurate and reproducible tunnel,
      which is essential for successful ACL reconstruction surgery.

PMID- 24748612
TI  - Streptococcus mutans extracellular DNA is upregulated during growth in biofilms,
      actively released via membrane vesicles, and influenced by components of the
      protein secretion machinery.
AB  - Streptococcus mutans, a major etiological agent of human dental caries, lives
      primarily on the tooth surface in biofilms. Limited information is available
      concerning the extracellular DNA (eDNA) as a scaffolding matrix in S. mutans
      biofilms. This study demonstrates that S. mutans produces eDNA by multiple
      avenues, including lysis-independent membrane vesicles. Unlike eDNAs from cell
      lysis that were abundant and mainly concentrated around broken cells or cell
      debris with floating open ends, eDNAs produced via the lysis-independent pathway
      appeared scattered but in a structured network under scanning electron
      microscopy. Compared to eDNA production of planktonic cultures, eDNA production
      in 5- and 24-h biofilms was increased by >3- and >1.6-fold, respectively. The
      addition of DNase I to growth medium significantly reduced biofilm formation. In
      an in vitro adherence assay, added chromosomal DNA alone had a limited effect on
      S. mutans adherence to saliva-coated hydroxylapatite beads, but in conjunction
      with glucans synthesized using purified glucosyltransferase B, the adherence was
      significantly enhanced. Deletion of sortase A, the transpeptidase that covalently
      couples multiple surface-associated proteins to the cell wall peptidoglycan,
      significantly reduced eDNA in both planktonic and biofilm cultures. Sortase A
      deficiency did not have a significant effect on membrane vesicle production;
      however, the protein profile of the mutant membrane vesicles was significantly
      altered, including reduction of adhesin P1 and glucan-binding proteins B and C.
      Relative to the wild type, deficiency of protein secretion and membrane protein
      insertion machinery components, including Ffh, YidC1, and YidC2, also caused
      significant reductions in eDNA. 

PMID- 24748613
TI  - Txc, a new type II secretion system of Pseudomonas aeruginosa strain PA7, is
      regulated by the TtsS/TtsR two-component system and directs specific secretion of
      the CbpE chitin-binding protein.
AB  - We present here the functional characterization of a third complete type II
      secretion system (T2SS) found in newly sequenced Pseudomonas aeruginosa strain
      PA7. We call this system Txc (third Xcp homolog). This system is encoded by the
      RGP69 region of genome plasticity found uniquely in strain PA7. In addition to
      the 11 txc genes, RGP69 contains two additional genes encoding a possible T2SS
      substrate and a predicted unorthodox sensor protein, TtsS (type II secretion
      sensor). We also identified a gene encoding a two-component response regulator
      called TtsR (type II secretion regulator), which is located upstream of the ttsS
      gene and just outside RGP69. We show that TtsS and TtsR constitute a new and
      functional two-component system that controls the production and secretion of the
      RGP69-encoded T2SS substrate in a Txc-dependent manner. Finally, we demonstrate
      that this Txc-secreted substrate binds chitin, and we therefore name it CbpE
      (chitin-binding protein E). 

PMID- 24748614
TI  - Hypermotility in Clostridium perfringens strain SM101 is due to spontaneous
      mutations in genes linked to cell division.
AB  - Clostridium perfringens is a Gram-positive anaerobic pathogen of humans and
      animals. Although they lack flagella, C. perfringens bacteria can still migrate
      across surfaces using a type of gliding motility that involves the formation of
      filaments of bacteria lined up in an end-to-end conformation. In strain SM101,
      hypermotile variants are often found arising from the edges of colonies on agar
      plates. Hypermotile cells are longer than wild-type cells, and video microscopy
      of their gliding motility suggests that they form long, thin filaments that move
      rapidly away from a colony, analogously to swarmer cells in bacteria with
      flagella. To identify the cause(s) of the hypermotility phenotype, the genome
      sequences of normal strains and their direct hypermotile derivatives were
      determined and compared. Strains SM124 and SM127, hypermotile derivatives of
      strains SM101 and SM102, respectively, contained 10 and 6 single nucleotide
      polymorphisms (SNPs) relative to their parent strains. While SNPs were located in
      different genes in the two sets of strains, one feature in common was mutations
      in cell division genes, an ftsI homolog in strain SM124 (CPR_1831) and a minE
      homolog in strain SM127 (CPR_2104). Complementation of these mutations with wild
      type copies of each gene restored the normal motility phenotype. A model
      explaining the principles underlying the hypermotility phenotype is presented. 

PMID- 24748615
TI  - Rod-to-hook transition for extracellular flagellum assembly is catalyzed by the L
      ring-dependent rod scaffold removal.
AB  - In Salmonella, the rod substructure of the flagellum is a periplasmic driveshaft
      that couples the torque generated by the basal body motor to the extracellular
      hook and filament. The rod subunits self-assemble, spanning the periplasmic space
      and stopping at the outer membrane when a mature length of ~22 nm is reached.
      Assembly of the extracellular hook and filament follow rod completion. Hook
      initiation requires that a pore forms in the outer membrane and that the rod
      capping protein, FlgJ, dislodges from the tip of the distal rod and is replaced
      with the hook-capping protein, FlgD. Approximately 26 FlgH subunits form the L
      ring around the distal rod that creates the pore through which the growing
      flagellum will elongate from the cell body. The function of the L-ring in the
      mature flagellum is also thought to act as a bushing for the rotating rod. Work
      presented here demonstrates that, in addition to outer membrane pore formation, L
      ring formation catalyzes the removal of the FlgJ rod cap. Rod cap removal allows
      the hook cap to assemble at the rod tip and results in the transition from rod
      completion in the periplasm to extracellular hook polymerization. By coupling the
      rod-to-hook switch to outer membrane penetration, FlgH ensures that hook and
      filament polymerization is initiated at the appropriate spatial and temporal
      point in flagellar biosynthesis.

PMID- 24748616
TI  - Sulfolobus replication factor C stimulates the activity of DNA polymerase B1.
AB  - Replication factor C (RFC) is known to function in loading proliferating cell
      nuclear antigen (PCNA) onto primed DNA, allowing PCNA to tether DNA polymerase
      for highly processive DNA synthesis in eukaryotic and archaeal replication. In
      this report, we show that an RFC complex from the hyperthermophilic archaea of
      the genus Sulfolobus physically interacts with DNA polymerase B1 (PolB1) and
      enhances both the polymerase and 3'-5' exonuclease activities of PolB1 in an ATP
      independent manner. Stimulation of the PolB1 activity by RFC is independent of
      the ability of RFC to bind DNA but is consistent with the ability of RFC to
      facilitate DNA binding by PolB1 through protein-protein interaction. These
      results suggest that Sulfolobus RFC may play a role in recruiting DNA polymerase
      for efficient primer extension, in addition to clamp loading, during DNA
      replication. 

PMID- 24748617
TI  - Construction and characterization of a Borrelia burgdorferi strain with
      conditional expression of the essential telomere resolvase, ResT.
AB  - Borrelia species are unique in the bacterial world in possessing segmented
      genomes which sometimes contain over 20 genetic elements. Most elements are
      linear and contain covalently closed hairpin ends requiring a specialized
      process, telomere resolution, for their generation. Hairpin telomere resolution
      is mediated by the telomere resolvase, ResT. Although the process has been
      studied extensively in vitro, the essential nature of the resT gene has precluded
      biological studies to further probe the role of ResT. In this work, we have
      generated a B. burgdorferi strain that carries an isopropyl-beta-d
      thiogalactopyranoside (IPTG)-inducible resT gene controlled by a tightly
      regulated promoter. ResT is expressed in this strain at ~14,000 monomers per
      cell, similar to the ~15,000 monomers observed for the parental strain. We
      demonstrate ResT depletion with a half-life of 16 h upon IPTG washout. ResT
      depletion resulted in arrested growth 48 h after washout. Interestingly, not all
      spirochetes died after ResT washout, and at least 15% remained quiescent and
      could be resuscitated even at 2 weeks postwashout. Significant levels of DNA
      synthesis were not observed upon growth arrest, suggesting that ResT might
      interact directly or indirectly with factors controlling the initiation or
      elongation of DNA synthesis. Analysis of the linear plasmids lp17 and lp28-2
      showed that the linear forms of these plasmids began to disappear and be replaced
      by higher-molecular-weight forms by 24 h post-IPTG washout. Treatment of DNA from
      the ResT-depleted strain with ResT in vitro revealed the presence of replicated
      telomeres expected in replication intermediates.

PMID- 24748618
TI  - A conserved suppressor mutation in a tryptophan auxotroph results in
      dysregulation of Pseudomonas quinolone signal synthesis.
AB  - Pseudomonas aeruginosa is a common nosocomial pathogen that relies on three cell
      to-cell signals to regulate multiple virulence factors. The Pseudomonas quinolone
      signal (PQS; 2-heptyl-3-hydroxy-4-quinolone) is one of these signals, and it is
      known to be important for P. aeruginosa pathogenesis. PQS is synthesized in a
      multistep reaction that condenses anthranilate and a fatty acid. In P.
      aeruginosa, anthranilate is produced via the kynurenine pathway and two separate
      anthranilate synthases, TrpEG and PhnAB, the latter of which is important for PQS
      synthesis. Others have previously shown that a P. aeruginosa tryptophan auxotroph
      could grow on tryptophan-depleted medium with a frequency of 10(-5) to 10(-6).
      These revertants produced more pyocyanin and had increased levels of phnA
      transcript. In this study, we constructed similar tryptophan auxotroph revertants
      and found that the reversion resulted from a synonymous G-to-A nucleotide
      mutation within pqsC. This change resulted in increased pyocyanin and decreased
      PQS, along with an increase in the level of the pqsD, pqsE, and phnAB
      transcripts. Reporter fusion and reverse transcriptase PCR studies indicated that
      a novel transcript containing pqsD, pqsE, and phnAB occurs in these revertants,
      and quantitative real-time PCR experiments suggested that the same transcript
      appears in the wild-type strain under nutrient-limiting conditions. These results
      imply that the PQS biosynthetic operon can produce an internal transcript that
      increases anthranilate production and greatly elevates the expression of the PQS
      signal response protein PqsE. This suggests a novel mechanism to ensure the
      production of both anthranilate and PQS-controlled virulence factors. 

PMID- 24748619
TI  - Towards modelling the flexible timing of shoot development: simulation of maize
      organogenesis based on coordination within and between phytomers.
AB  - BACKGROUND AND AIMS: Experimental evidence challenges the approximation, central
      in crop models, that developmental events follow a fixed thermal time schedule,
      and indicates that leaf emergence events play a role in the timing of
      development. The objective of this study was to build a structural development
      model of maize (Zea mays) based on a set of coordination rules at organ level
      that regulate duration of elongation, and to show how the distribution of leaf
      sizes emerges from this. METHODS: A model of maize development was constructed
      based on three coordination rules between leaf emergence events and the dynamics
      of organ extension. The model was parameterized with data from maize grown at a
      low plant population density and tested using data from maize grown at high
      population density. KEY RESULTS: The model gave a good account of the timing and
      duration of organ extension. By using initial conditions associated with high
      population density, the model reproduced well the increase in blade elongation
      duration and the delay in sheath extension in high-density populations compared
      with low-density populations. Predictions of the sizes of sheaths at high density
      were accurate, whereas predictions of the dynamics of blade length were accurate
      up to rank 9; moderate overestimation of blade length occurred at higher ranks.
      CONCLUSIONS: A set of simple rules for coordinated growth of organs is sufficient
      to simulate the development of maize plant structure without taking into account
      any regulation by assimilates. In this model, whole-plant architecture is shaped
      through initial conditions that feed a cascade of coordination events.

PMID- 24748621
TI  - Allostery and conformational dynamics in cAMP-binding acyltransferases.
AB  - Mycobacteria harbor unique proteins that regulate protein lysine acylation in a
      cAMP-regulated manner. These lysine acyltransferases from Mycobacterium smegmatis
      (KATms) and Mycobacterium tuberculosis (KATmt) show distinctive biochemical
      properties in terms of cAMP binding affinity to the N-terminal cyclic nucleotide
      binding domain and allosteric activation of the C-terminal acyltransferase
      domain. Here we provide evidence for structural features in KATms that account
      for high affinity cAMP binding and elevated acyltransferase activity in the
      absence of cAMP. Structure-guided mutational analysis converted KATms from a cAMP
      regulated to a cAMP-dependent acyltransferase and identified a unique asparagine
      residue in the acyltransferase domain of KATms that assists in the enzymatic
      reaction in the absence of a highly conserved glutamate residue seen in Gcn5
      related N-acetyltransferase-like acyltransferases. Thus, we have identified
      mechanisms by which properties of similar proteins have diverged in two species
      of mycobacteria by modifications in amino acid sequence, which can dramatically
      alter the abundance of conformational states adopted by a protein. 

PMID- 24748622
TI  - Force feeding forces us to confront our professional ethical obligations.

PMID- 24748620
TI  - Exposure-affecting factors of dairy farmers' exposure to inhalable dust and
      endotoxin.
AB  - INTRODUCTION: Studies on determinants of dairy farmers' exposure to dust and
      endotoxin have been sparse and so far none has addressed the combined effect of
      tasks and farm characteristics. OBJECTIVE: To study whether and how work tasks
      and specific stable characteristics influence the level of dairy farmers'
      personal exposure to inhalable dust and endotoxin. METHODS: We applied an
      observational design involving full-shift repeated personal measurements of
      inhalable dust and endotoxin exposure among 77 subjects (owners and farm workers)
      from 26 dairy farms. Performed tasks were self-registered in activity diaries,
      and information on stable characteristics was collected through personal
      interviews and walk-through surveys. Associations between exposure, tasks, and
      stable characteristics were examined in linear mixed-effect models with
      individual and farm treated as random effects. Separate as well as combined
      models for tasks and stable characteristics were elaborated. RESULTS: The 124
      personal samples collected had a geometric mean level (geometric standard
      deviation) of 360 EU m(-3) (3.8) for endotoxin exposure and of 1.0mg m(-3) (2.7)
      for dust exposure. Identified factors that increased endotoxin exposure included
      a lower outdoor temperature and use of slope-based or back-flushed slurry systems
      along with milking, distribution of bedding, and handling of feed and seeds in
      barns. For dust, exposure was higher when fully automatic (robotic) milking was
      used and during re-penning of animals, handling of feed and seeds, handling of
      silos and when distributing bedding. Dust exposure increased also as a result of
      use of rail feed dispensers in a model without fully automatic milking.
      CONCLUSIONS: The current exposure to dust and in particular endotoxin among
      Danish dairy farmers demand effective strategies to reduce their exposure. The
      present findings suggest that future interventions should focus on feeding and
      manure handling systems. Use of respirators during handling of feed and
      distribution of bedding should be advised until adequate risk management measures
      have been established. The expected increased use of fully automatic milking in
      the future might increase dust exposure of dairy farmers.

PMID- 24748623
TI  - Prevalence of malnutrition and current use of nutrition support in cancer patient
      study.

PMID- 24748624
TI  - Does glutamine really kill?

PMID- 24748625
TI  - Letter to the editor response.

PMID- 24748626
TI  - Prevalence of malnutrition and current use of nutrition support in patients with
      cancer.
AB  - BACKGROUND AND AIMS: The aim of this study was to evaluate on 1 day the
      prevalence of malnutrition in different types of cancer and the use of nutrition
      support in patients with cancer. METHODS: A 1-day prevalence survey was carried
      out in 154 French hospital wards. Malnutrition was defined as a body mass index
      (BMI) <18.5 in patients <75 years old or <21 in patients >=75 years old and/or
      body weight loss >10% since disease onset. Oral food intake was measured using a
      visual analog scale. RESULTS: Nutrition status was collected for 1903 patients
      (1109 men and 794 women, 59.3 +/- 13.2 years). Cancer was local in 25%, regional
      in 31%, and metastatic in 44% of patients. Performance status was 0 or 1 in
      49.8%, 2 in 23.7%, 3 or 4 in 19.6% and not available in 6.5% of patients.
      Overall, 39% of patients were malnourished. The prevalence of malnutrition by
      disease site was as follows: head and neck, 48.9%; leukemia/lymphoma, 34.0%;
      lung, 45.3%; colon/rectum, 39.3%; esophagus and/or stomach, 60.2%; pancreas,
      66.7%; breast, 20.5%; ovaries/uterus, 44.8%; and prostate, 13.9%. Regional cancer
      (odds ratio, 1.96; 95% confidence interval, 1.42-2.70), metastatic cancer (2.97;
      2.14-4.12), previous chemotherapy (1.41; 1.05-1.89), and previous radiotherapy
      (1.53; 1.21-1.92) were associated with malnutrition. Only 28.4% of non
      malnourished patients and 57.6% of malnourished patients received nutrition
      support. In all, 55% of patients stated that they were eating less than before
      the cancer, while 41.4% of patients stated that they had received nutrition
      counseling. CONCLUSIONS: The prevalence of malnutrition is high in patients with
      cancer, and systematic screening for and treatment of malnutrition is necessary.

PMID- 24748627
TI  - JPEN Journal Club. Association vs Causation.

PMID- 24748628
TI  - Response to: 'The autoantibody repertoire in periodontitis: a role in the
      induction of autoimmunity to citrullinated proteins in rheumatoid arthritis?
      Antibodies against uncitrullinated peptides seem to occur prior to the antibodies
      to the corresponding citrullinated peptides' by Brink et al.

PMID- 24748629
TI  - A phase 2, randomised, placebo-controlled clinical trial of blisibimod, an
      inhibitor of B cell activating factor, in patients with moderate-to-severe
      systemic lupus erythematosus, the PEARL-SC study.
AB  - OBJECTIVE: To evaluate the efficacy and safety of subcutaneous blisibimod, an
      inhibitor of B cell activating factor, in patients with systemic lupus
      erythematosus (SLE) in a dose-ranging Phase 2b clinical trial. METHODS: 547
      patients with SLE with anti-double stranded DNA or antinuclear antibodies and
      Safety of Estrogens in Lupus Erythematosus National Assessment-SLE Disease
      Activity Index (SELENA-SLEDAI) score >=6 at baseline were randomised to receive
      placebo or blisibimod at one of 3 dose levels. The primary end point, measured at
      Week 24, was the SLE Responder Index-5 (SRI-5, meeting established SRI criteria
      but with >=5 point improvement in SELENA-SLEDAI). RESULTS: Although SRI-5
      response rates were not significantly improved in the pooled blisibimod groups
      compared with placebo, they were higher in subjects randomised to the highest
      dose of blisibimod (200 mg once-weekly (QW)) compared with pooled placebo, from
      Week 16 to Week 24, reaching statistical significance at Week 20 (p=0.02). SRI
      response rates compared with placebo were higher still in subjects who attained
      SELENA-SLEDAI improvements of >=8, and in a subgroup of patients with severe
      disease (SELENA-SLEDAI >=10 and receiving corticosteroids at baseline). In
      subjects with protein:creatine ratios of 1-6 at baseline, significant reductions
      in proteinuria were observed with blisibimod. Significant (p<0.01) changes in
      anti-double stranded DNA antibodies, complement C3 and C4, and reductions in B
      cells were observed with blisibimod.No imbalances in serious adverse events or
      infections (4/280 and 3/266), deaths (4/280 and 3/266) and malignancies (2/280
      and 2/266) were reported for blisibimod compared with placebo. CONCLUSIONS: This
      study successfully identified a safe, effective and convenient dose, study
      population and end point for evaluation of blisibimod effect in Phase 3. TRIAL
      REGISTRATION NUMBER: NCT01162681.

PMID- 24748630
TI  - Clinical efficacy, radiographic and safety findings through 5 years of
      subcutaneous golimumab treatment in patients with active psoriatic arthritis:
      results from a long-term extension of a randomised, placebo-controlled trial (the
      GO-REVEAL study).
AB  - OBJECTIVES: Assess golimumab's long-term efficacy/safety in psoriatic arthritis
      (PsA). METHODS: Adults with active PsA (>=3 swollen and tender joints, active
      psoriasis) were randomly assigned to subcutaneous placebo, golimumab 50 mg, or
      golimumab 100 mg every 4 weeks (q4wks) through wk20. All patients received
      golimumab 50 mg or 100 mg q4wks from wk24 forward. Methotrexate was allowed and
      taken by approximately half the patients. Findings through 5 years are reported
      herein. Efficacy assessments included >=20% improvement in American College of
      Rheumatology (ACR20) response, C-reactive-protein-based, 28-joint-count Disease
      Activity Score (DAS28-CRP) response, >=75% improvement in Psoriasis Area and
      Severity Index (PASI75) scores, and PsA-modified Sharp/van der Heijde scores
      (SHSs). RESULTS: 126/405 (31%) randomised patients discontinued treatment through
      wk252. Golimumab was effective in maintaining clinical improvement through year-5
      (ACR20: 62.8-69.9%, DAS28-CRP: 75.2-84.9% for randomised patients; PASI75: 60.8
      72.2% among randomised patients with >=3% body surface area involvement) and
      inhibiting radiographic progression (mean changes in PsA-modified SHS: 0.1-0.3)
      among patients with radiographic data. While concomitant methotrexate did not
      affect ACR20/PASI75, it appeared to reduce radiographic progression. No new
      safety signals were identified. Antibodies-to-golimumab occurred in 1.8%/10.0% of
      patients with/without methotrexate). CONCLUSIONS: Long-term golimumab
      safety/efficacy in PsA was demonstrated through 5 years. TRIAL REGISTRATION
      NUMBER: NCT00265096.

PMID- 24748631
TI  - Comment on "Killer Ig-like receptor 2DL4 does not mediate NK Cell IFN-gamma
      responses to soluble HLA-G preparations".

PMID- 24748632
TI  - Response to comment on "killer Ig-like receptor 2DL4 does not mediate NK cell IFN
      gamma responses to soluble HLA-G preparations".

PMID- 24748633
TI  - Development and implementation of papillomavirus prophylactic vaccines.
AB  - Translation of basic scientific findings into practical patient outcomes is a
      significant exercise even when the goal is conceptually straightforward, as in
      the development of a vaccine for an infectious disease. Recognition of the
      association of cervical cancer with papillomavirus infection encouraged
      development of a vaccine to help with prevention of this very common cancer,
      causing over 250,000 deaths each year worldwide. To introduce a vaccine program,
      it was however necessary to develop a technology for making viral Ag, demonstrate
      that systemic immunization could provide mucosal surface protection in the
      genital tract, develop assays for vaccine potency, and understand enough about
      the epidemiology and natural history of the infection to plan effective
      intervention strategies. This process took ~25 years. The major hurdle, now that
      effective vaccines are available, is to ensure their deployment in the countries
      where they are most needed. The development and deployment of human
      papillomavirus vaccines demonstrate the benefits of collaborative research
      activity across the globe, and between academia and industry, to translate
      scientific discoveries into public health benefits. 

PMID- 24748634
TI  - A clue to antigen receptor tails.

PMID- 24748635
TI  - Pillars article: antigen receptor tail clue. Nature. 1989. 338: 383-384.

PMID- 24748636
TI  - An overview of the intrathymic intricacies of T cell development.
AB  - The generation of a functional and diverse repertoire of T cells occurs in the
      thymus from precursors arriving from the bone marrow. In this article, we
      introduce the various stages of mouse thymocyte development and highlight recent
      work using various in vivo, and, where appropriate, in vitro models of T cell
      development that led to discoveries in the regulation afforded by transcription
      factors and receptor-ligand signaling pathways in specifying, maintaining, and
      promoting the T cell lineage and the production of T cells. This review also
      discusses the role of the thymic microenvironment in providing a niche for the
      successful development of T cells. In particular, we focus on advances in Notch
      signaling and developments in Notch ligand interactions in this process. 

PMID- 24748637
TI  - Vitamin D treatment in calcium-deficiency rickets: a randomised controlled trial.
AB  - OBJECTIVE: To determine whether children with calcium-deficiency rickets have a
      better response to treatment with vitamin D and calcium than with calcium alone.
      DESIGN: Randomised controlled trial. SETTING: Jos University Teaching Hospital,
      Jos, Nigeria. POPULATION: Nigerian children with active rickets treated with
      calcium carbonate as limestone (approximately 938 mg elemental calcium twice
      daily) were, in addition, randomised to receive either oral vitamin D2 50,000 IU
      (Ca+D, n=44) or placebo (Ca, n=28) monthly for 24 weeks. MAIN OUTCOME MEASURE:
      Achievement of a 10-point radiographic severity score <=1.5 and serum alkaline
      phosphatase <=350 U/L. RESULTS: The median (range) age of enrolled children was
      46 (15-102) months, and baseline characteristics were similar in the two groups.
      Mean (+/-SD) 25-hydroxyvitamin D (25(OH)D) was 30.2+/-13.2 nmol/L at baseline,
      and 29 (43%) had values <30 nmol/L. Baseline alkaline phosphatase and
      radiographic scores were unrelated to vitamin D status. Of the 68 children (94%
      of original cohort) who completed 24 weeks of treatment, 29 (67%) in the Ca+D
      group and 11 (44%) in the Ca group achieved the primary outcome (p=0.06).
      Baseline 25(OH)D did not alter treatment group effects (p=0.99 for interaction).
      At the end of 24 weeks, 25(OH)D values were 55.4+/-17.0 nmol/L and 37.9+/-20.0
      nmol/L in the Ca+D and Ca groups, respectively, (p<0.001). In the Ca+D and Ca
      groups, the final 25(OH)D concentration was greater in those who achieved the
      primary outcome (56.4+/-17.2 nmol/L) than in those who did not (37.7+/-18.5
      nmol/L, p<0.001). CONCLUSIONS: In children with calcium-deficiency rickets, there
      is a trend for vitamin D to improve the response to treatment with calcium
      carbonate as limestone, independent of baseline 25(OH)D concentrations. TRIAL
      REGISTRATION NUMBER: ClinicalTrials.gov NCT00949832.

PMID- 24748638
TI  - Therapeutic research in low-income countries: studying trial communities.
AB  - Social scientists undertaking studies of transnational medical research in
      developing countries focus on 'trial communities': networks of funders,
      institutions, researchers, clinical staff, fieldworkers and study participants.
      They relate these to the political economy that brings powerful research
      resources to poor settings. Whereas bioethicists tend to consider universal
      ethical requirements, social scientists examine how ethics are practiced in given
      situations in the light of the concerns and interests held by different parties
      involved in medical research. In conditions of poverty, high morbidity and weak
      public health services, research subjects are heavily induced by the prospect of
      high quality medical care and other benefits that researchers seem to offer.
      Studies of medical research undertaken by well-established internationally funded
      institutions in Africa show that parents are keen to have their children 'join'
      projects at these organisations. They assess benefits and risks less in terms of
      specific research projects and more in terms of their overall trust in the care
      these institutions are known to have provided previously for others in the
      community. Bioethics should widen its scope beyond concern with protecting
      individual subjects from the risks of specific research projects. It should
      recognise that clinical and research functions are indistinguishable for many
      participants, who want information on results of clinical investigations and
      sustained support for improving the health of their children. 

PMID- 24748639
TI  - Non-cutaneous conditions clinicians might mistake for abuse.
AB  - OBJECTIVE: To determine the frequency of non-cutaneous mimics identified in a
      large, multicentre cohort of children evaluated for physical abuse. METHODS:
      Prospectively planned, secondary analysis of 2890 physical abuse consultations
      from the Examining Siblings To Recognize Abuse (ExSTRA) research network. Data
      for each enrolled subject were entered at the child abuse physician's diagnostic
      disposition. Physicians prospectively documented whether or not a 'mimic' was
      identified and the perceived likelihood of abuse. Mimics were divided into 3
      categories: (1) strictly cutaneous mimics, (2) strictly non-cutaneous mimics and
      (3) cutaneous and non-cutaneous mimics. Perceived likelihood of abuse was
      described for each child on a 7-point scale (7=definite abuse). RESULTS: Among
      2890 children who were evaluated for physical abuse, 137 (4.7%) had mimics
      identified; 81 mimics (59.1% of mimics and 2.8% of the whole cohort) included non
      cutaneous components. Six subjects (7.4%) were assigned a high level of abuse
      concern and 17 (20.1%) an intermediate level despite the identification of a
      mimic. Among the identified mimics, 28% were classified as metabolic bone
      disease, 20% haematologic/vascular, 16% infectious, 10% skeletal dysplasia, 9%
      neurologic, 5% oncologic, 2% gastrointestinal and 10% other.
      Osteomalacia/osteoporosis was the most common non-cutaneous mimic followed by
      vitamin D deficiency. CONCLUSIONS: A wide variety of mimics exist affecting most
      disease categories. Paediatric care providers need to be familiar with these
      conditions to avoid pitfalls in the diagnosis of physical abuse. Identification
      of a mimic does not exclude concurrent abuse.

PMID- 24748640
TI  - Why children do not receive treatment.

PMID- 24748641
TI  - Safety of medicines used for ADHD in children: a review of published prospective
      clinical trials.
AB  - OBJECTIVE: To assess the long-term safety of drugs for attention deficit
      hyperactivity disorder (ADHD). METHODS: A bibliographic search was performed in
      the MEDLINE, EMBASE and PsycINFO databases for prospective studies evaluating the
      incidence of adverse events (AEs) in children and adolescents treated for ADHD.
      RESULTS: A total of six prospective studies that monitored drug safety during
      therapy for at least 12 weeks were retrieved. The drugs studied were atomoxetine
      (two studies, 802 patients), osmotic-controlled released oral methylphenidate
      formulation (two studies, 512 patients), extended release formulation of mixed
      amphetamine salts (one study, 568 patients) and transdermal methylphenidate (one
      study, 326 patients). Heterogeneity was found in the duration of follow-up
      (ranging between 1 and 4 years) and in the way data were reported. The rate of
      treatment-related AEs ranged from 58% to 78%, and the rate of discontinuation due
      to AEs ranged from 8% to 25% of the children. Decreased appetite, insomnia,
      headache and abdominal pain were the most common AEs observed. Most AEs and cases
      of discontinuation occurred during the first few months of treatment.
      CONCLUSIONS: Few studies evaluated the long-term safety of drugs for ADHD.
      Heterogeneity in follow-up duration and in data reporting made comparing
      different studies and drugs difficult. A systematic monitoring of long-term
      safety is needed.

PMID- 24748642
TI  - Multiple cerebral aneurysms after myxomatous stroke.

PMID- 24748643
TI  - Painful nodules on the soles in a 9-year-old boy.

PMID- 24748644
TI  - Angiogenesis in superficial esophageal squamous cell carcinoma: assessment of
      microvessel density based on immunostaining for CD34 and CD105.
AB  - OBJECTIVE: The esophagus is the only organ where changes in the superficial
      microvasculature from normal squamous epithelium to invasive cancer are evident
      by magnifying endoscopy. We investigated in detail the features of angiogenesis
      in early-stage esophageal cancer using CD34 and CD105 immunostaining, and also
      the correlation between angiogenesis and mononuclear cell infiltration. MATERIALS
      AND METHODS: Using 10 samples of normal squamous epithelium, 7 samples of low
      grade intraepithelial neoplasia, and 45 samples of superficial esophageal cancer,
      we determined the microvessel density at hot spots showing positive staining for
      CD34 and CD105. We observed the histological features of CD34- and CD105-positive
      microvessels that corresponded to observations made by magnifying endoscopy. We
      then investigated the correlation between microvessel density and each
      histological situation or the grade of mononuclear cell infiltration. RESULTS:
      The histological features of CD34- and CD105-positive microvessels were able to
      explain the morphological changes in the microvasculature during cancer
      progression observed by magnifying endoscopy. The microvessel density for CD34 or
      CD105 was significantly correlated with each of the histological types (P <
      0.001, rS = 0.51 and 0.76, respectively). Mononuclear cell infiltration at CD105
      hot spots was most frequent in M1 and M2 cancer (94.7%). The correlation between
      the degree of mononuclear cell infiltration and microvessel density for CD105
      staining was also significant (P < 0.001, rS = 0.49). CONCLUSIONS: The
      microvessel density based on CD34 and CD105 immunostaining can be used to
      corroborate observations of superficial esophageal squamous cell carcinoma made
      by magnifying endoscopy. Mononuclear cell infiltration may play an important role
      in angiogenesis at the early stage of cancer progression.

PMID- 24748645
TI  - Thymine DNA glycosylase promotes transactivation of beta-catenin/TCFs by
      cooperating with CBP.
AB  - Thymine DNA glycosylase (TDG), an enzyme that initiates the repair of G/T and G/U
      mismatches, has been lately found crucial in embryonic development to maintain
      epigenetic stability and facilitate the active DNA demethylation. Here we report
      a novel role of TDG in Wnt signaling as a transcriptional coactivator of beta
      catenin/TCFs complex. Our data show that TDG binds to the transcriptional factor
      family LEF1/TCFs and potentiates beta-catenin/TCFs transactivation, while TDG
      depletion suppresses Wnt3a-stimulated reporter activity or target gene
      transcription. Next, we show that CBP, a known coactivator, is also required for
      TDG function through forming a cooperative complex on target promoters. Moreover,
      there is an elevation of TDG levels in human colon cancer tissue, and knockdown
      of TDG inhibits proliferation of the colon cells. Overall, our results reveal
      that TDG, as a new coactivator, promotes beta-catenin/TCFs transactivation and
      functionally cooperates with CBP in canonical Wnt signaling. 

PMID- 24748646
TI  - HLA alleles as biomarkers of high-titre neutralising antibodies to interferon
      beta therapy in multiple sclerosis.
AB  - BACKGROUND: Recombinant interferon beta (IFNbeta) is a first-line therapy for
      relapsing-remitting multiple sclerosis (MS), with a proven effect on the
      inflammatory activity. Neutralising antibodies against IFNbeta (NAbs) promote a
      loss of IFNbeta bioactivity in a titre-dependent way and their development was
      associated with certain human leucocyte antigen (HLA) alleles. We investigated
      the contribution conferred by HLA alleles on the development of NAbs in
      independent cohorts of Southern Europe. METHODS: Serum NAbs from 610 MS patients
      with HLA-genotype data were evaluated by cytopathic effect assay: negative tests
      included at least one negative result (NAb titres<20 NU/mL) after 1 year
      treatment; NAb-titres >=20 NU/mL were positive tests and NAb titres >=150 NU/mL
      in any test were classified as high-titre positives. RESULTS: The combined
      presence of DRB1*07/DQA1*02 with A*26 or B*14 was found in 20% of patients with
      NAbs at high titres, but only in 5.4% of NAb-negative patients (p=0.00052, OR
      (95% CI) 4.34 (1.85 to 10.13)). The DRB1*04:01 allele was also more frequently
      carried by patients with high titres of NAbs (10% vs 4.5%; p=0.046, OR (95% CI)
      2.38 (0.93 to 5.92)). The alleles carried at a significantly lower frequency in
      patients with high persistent NAbs corresponded to the A*11 allele (3.3% vs
      13.8%; p=0.023, OR (95% CI) 0.22 (0.02 to 0.87)), as well as the
      DRB1*03/DQA1*05/DQB1*02 haplotype (16.3% vs 26.8%; p=0.02, OR (95% CI) 0.53 (0.27
      to 1.03)) and the DRB1*13/DQA1*01:03/DQB1*06:03 haplotype (2.5% vs 9.1%; p=0.045,
      OR (95% CI) 0.25 (0.03 to 1.02)). CONCLUSIONS: 50% of the studied MS patients
      carried some of the five independently associated HLA allele/allele combinations
      described in this work. This relevant percentage of patients could benefit a
      therapeutic decision.

PMID- 24748647
TI  - Assessing recovery and disability after physical trauma: the Pediatric Injury
      Functional Outcome Scale.
AB  - OBJECTIVE: To establish reliability and validity of the Pediatric Injury
      Functional Outcome Scale (PIFOS), a brief injury-specific rating scale covering
      motor, self-care, communication, social-emotional, cognition, physical, and
      academic areas. METHODS: In a prospective longitudinal study, the PIFOS
      structured interview was administered to parents of children 3-15 years of age at
      3 and 12 months after hospitalization for traumatic brain injury (TBI) or
      orthopedic injury (OI). RESULTS: The total score had good internal consistency
      (alpha = .90-.93) and inter-rater reliability (alpha = .90) and correlated
      significantly with injury severity and neurodevelopmental outcomes. Generalized
      linear modeling showed the PIFOS was sensitive to the type and severity of
      injury, showed specific initial and persisting difficulties following TBI and OI,
      and was responsive to change during the first year after injury. Both groups had
      residual difficulties with coordination, emotionality, social participation, and
      discomfort. CONCLUSION: The PIFOS is useful in examining recovery in natural
      history and intervention studies.

PMID- 24748649
TI  - 'My child will never initiate Ultimate Harm': an argument against moral
      enhancement.
AB  - Recently, there has been a lot of philosophical work published on the morality of
      moral enhancement. One thing that tends to get overlooked in this literature is
      that there are many different potential methods of morally enhancing humans, and
      a blanket moral assessment of them may not be warranted. Here I focus on one mode
      of moral enhancement, namely, prenatal genetic moral enhancement, and offer a
      normative assessment of it. I argue that there is good reason to adopt a parent
      centred perspective (as opposed to a social or state-centred perspective) towards
      the ethics of prenatal genetic moral enhancement, and, once we do so, that there
      is good reason to argue that prenatal genetic attempts at moral enhancement are
      morally problematic and ought not to be pursued. The main reasons for this have
      to do with the nature of moral enhancement research, and the idea that
      prospective parents are justified in not assuming that their children will be
      morally depraved. I leave it open as to whether other modes of morally enhancing
      humans fare better, morally speaking. 

PMID- 24748648
TI  - The membrane proteome of sensory cilia to the depth of olfactory receptors.
AB  - In the nasal cavity, the nonmotile cilium of olfactory sensory neurons (OSNs)
      constitutes the chemosensory interface between the ambient environment and the
      brain. The unique sensory organelle facilitates odor detection for which it
      includes all necessary components of initial and downstream olfactory signal
      transduction. In addition to its function in olfaction, a more universal role in
      modulating different signaling pathways is implicated, for example, in
      neurogenesis, apoptosis, and neural regeneration. To further extend our knowledge
      about this multifunctional signaling organelle, it is of high importance to
      establish a most detailed proteome map of the ciliary membrane compartment down
      to the level of transmembrane receptors. We detached cilia from mouse olfactory
      epithelia via Ca(2+)/K(+) shock followed by the enrichment of ciliary membrane
      proteins at alkaline pH, and we identified a total of 4,403 proteins by gel-based
      and gel-free methods in conjunction with high resolution LC/MS. This study is the
      first to report the detection of 62 native olfactory receptor proteins and to
      provide evidence for their heterogeneous expression at the protein level.
      Quantitative data evaluation revealed four ciliary membrane-associated candidate
      proteins (the annexins ANXA1, ANXA2, ANXA5, and S100A5) with a suggested function
      in the regulation of olfactory signal transduction, and their presence in ciliary
      structures was confirmed by immunohistochemistry. Moreover, we corroborated the
      ciliary localization of the potassium-dependent Na(+)/Ca(2+) exchanger (NCKX) 4
      and the plasma membrane Ca(2+)-ATPase 1 (PMCA1) involved in olfactory signal
      termination, and we detected for the first time NCKX2 in olfactory cilia. Through
      comparison with transcriptome data specific for mature, ciliated OSNs, we finally
      delineated the membrane ciliome of OSNs. The membrane proteome of olfactory cilia
      established here is the most complete today, thus allowing us to pave new avenues
      for the study of diverse molecular functions and signaling pathways in and out of
      olfactory cilia and thus to advance our understanding of the biology of sensory
      organelles in general. 

PMID- 24748650
TI  - Results of a self-assessment tool to assess the operational characteristics of
      research ethics committees in low- and middle-income countries.
AB  - PURPOSE: Many research ethics committees (RECs) have been established in low- and
      middle-income countries (LMICs) in response to increased research in these
      countries. How well these RECs are functioning remains largely unknown. Our
      objective was to assess the usefulness of a self-assessment tool in obtaining
      benchmarking data on the extent to which RECs are in compliance with recognised
      international standards. METHODS: REC chairs from several LMICs (Egypt, South
      Africa and India) were asked to complete an online self-assessment tool for RECs
      with a maximum score of 200. Individual responses were collected anonymously.
      RESULTS: The aggregate mean score was 137.4+/-35.8 (~70% of maximum score); mean
      scores were significantly associated with the presence of a budget (p<0.001), but
      not with duration of existence, frequency of meetings, or the presence of
      national guidelines. As a group, RECs achieved more than 80% of the maximum score
      for the following domains: submission processes and documents received, recording
      of meeting minutes, criteria for ethical review and criteria for informed
      consent. RECs achieved less than 80% of the maximum score for the following
      domains: institutional commitment, policies and procedures of the REC, membership
      composition and training, policies and procedures for protocol review, elements
      of a decision letter and criteria for continuing review. CONCLUSIONS: This study
      highlights areas where RECs from LMICs can improve to be in compliance with
      recommended international standards for RECs. The self-assessment tool provides
      valuable benchmarking data for RECs and can serve as a quality improvement method
      to help RECs enhance their operations.

PMID- 24748651
TI  - Platyzoan paraphyly based on phylogenomic data supports a noncoelomate ancestry
      of spiralia.
AB  - Based on molecular data three major clades have been recognized within Bilateria:
      Deuterostomia, Ecdysozoa, and Spiralia. Within Spiralia, small-sized and simply
      organized animals such as flatworms, gastrotrichs, and gnathostomulids have
      recently been grouped together as Platyzoa. However, the representation of
      putative platyzoans was low in the respective molecular phylogenetic studies, in
      terms of both, taxon number and sequence data. Furthermore, increased
      substitution rates in platyzoan taxa raised the possibility that monophyletic
      Platyzoa represents an artifact due to long-branch attraction. In order to
      overcome such problems, we employed a phylogenomic approach, thereby
      substantially increasing 1) the number of sampled species within Platyzoa and 2)
      species-specific sequence coverage in data sets of up to 82,162 amino acid
      positions. Using established and new measures (long-branch score), we
      disentangled phylogenetic signal from misleading effects such as long-branch
      attraction. In doing so, our phylogenomic analyses did not recover a monophyletic
      origin of platyzoan taxa that, instead, appeared paraphyletic with respect to the
      other spiralians. Platyhelminthes and Gastrotricha formed a monophylum, which we
      name Rouphozoa. To the exclusion of Gnathifera, Rouphozoa and all other
      spiralians represent a monophyletic group, which we name Platytrochozoa.
      Platyzoan paraphyly suggests that the last common ancestor of Spiralia was a
      simple-bodied organism lacking coelomic cavities, segmentation, and complex brain
      structures, and that more complex animals such as annelids evolved from such a
      simply organized ancestor. This conclusion contradicts alternative evolutionary
      scenarios proposing an annelid-like ancestor of Bilateria and Spiralia and
      several independent events of secondary reduction.

PMID- 24748652
TI  - Bayesian estimation of nonsynonymous/synonymous rate ratios for pairwise sequence
      comparisons.
AB  - The nonsynonymous/synonymous rate ratio (omega = d(N)/d(S)) is an important
      measure of the mode and strength of natural selection acting on nonsynonymous
      mutations in protein-coding genes. The simplest such analysis is the estimation
      of the d(N)/d(S) ratio using two sequences. Both heuristic counting methods and
      the maximum-likelihood (ML) method based on a codon substitution model are widely
      used for such analysis. However, these methods do not have nice statistical
      properties, as the estimates can be zero or infinity in some data sets, so that
      their means and variances are infinite. In large genome-scale comparisons, such
      extreme estimates (either 0 or infinity) of omega and sequence distance (t) are
      common. Here, we implement a Bayesian method to estimate omega and t in pairwise
      sequence comparisons. Using a combination of computer simulation and real data
      analysis, we show that the Bayesian estimates have better statistical properties
      than the ML estimates, because the prior on omega and t shrinks the posterior of
      those parameters away from extreme values. We also calculate the posterior
      probability for omega > 1 as a Bayesian alternative to the likelihood ratio test.
      The new method is computationally efficient and may be useful for genome-scale
      comparisons of protein-coding gene sequences.

PMID- 24748653
TI  - Centmitor-1, a novel acridinyl-acetohydrazide, possesses similar molecular
      interaction field and antimitotic cellular phenotype as rigosertib, on 01910.Na.
AB  - Mitosis is an attractive target for the development of new anticancer drugs. In a
      search for novel mitotic inhibitors, we virtually screened for low molecular
      weight compounds that would possess similar steric and electrostatic features,
      but different chemical structure than rigosertib (ON 01910.Na), a putative
      inhibitor of phosphoinositide 3-kinase (PI3K) and polo-like kinase 1 (Plk1)
      pathways. Highest scoring hit compounds were tested in cell-based assays for
      their ability to induce mitotic arrest. We identified a novel acridinyl
      acetohydrazide, here named as Centmitor-1 (Cent-1), that possesses highly similar
      molecular interaction field as rigosertib. In cells, Cent-1 phenocopied the
      cellular effects of rigosertib and caused mitotic arrest characterized by
      chromosome alignment defects, multipolar spindles, centrosome fragmentation, and
      activated spindle assembly checkpoint. We compared the effects of Cent-1 and
      rigosertib on microtubules and found that both compounds modulated microtubule
      plus-ends and reduced microtubule dynamics. Also, mitotic spindle forces were
      affected by the compounds as tension across sister kinetochores was reduced in
      mitotic cells. Our results showed that both Cent-1 and rigosertib target
      processes that occur during mitosis as they had immediate antimitotic effects
      when added to cells during mitosis. Analysis of Plk1 activity in cells using a
      Forster resonance energy transfer (FRET)-based assay indicated that neither
      compound affected the activity of the kinase. Taken together, these findings
      suggest that Cent-1 and rigosertib elicit their antimitotic effects by targeting
      mitotic processes without impairment of Plk1 kinase activity.

PMID- 24748654
TI  - Ectodomain-specific E-cadherin antibody suppresses skin SCC growth and reduces
      tumor grade: a multitargeted therapy modulating RTKs and the PTEN-p53-MDM2 axis.
AB  - Tumor cell survival consists of an intricate balance between cell growth and cell
      death pathways involving receptor tyrosine kinases [RTK; i.e., HER1-4, insulin
      like growth factor-1 receptor (IGF-1R), etc.], MDM2, and the tumor suppressor
      proteins phosphatase and tensin homolog deleted on chromosome ten (PTEN) and p53.
      We recently demonstrated that shedded E-cadherin extracellular domain fragment
      (sEcad) is a valid oncogenic target that is significantly increased in human
      clinical skin squamous cell cancers (SCC) samples, UV-induced mouse tumors, and
      cells and promotes tumor cell proliferation, migration, and invasion by
      interacting and activating with the HER-phosphatidylinositol 3-kinase (PI3K)-Akt
      mammalian target of rapamycin (mTOR) and mitogen-activated protein kinase (MAPK)
      axis. In resected human SCC tumors, we reported enhanced sEcad-HER1, sEcad-HER2,
      and sEcad-IGF-1R, but not FL-Ecad-RTK interactions. Here, we demonstrate that a
      sEcad antibody against the ectodomain of E-cadherin suppressed SCC growth and
      increased tumor differentiation in orthotopic cutaneous SCC xenografts by
      inhibiting proliferation and inducing apoptosis. A similar anti-sEcad antibody
      induced inhibition of proliferation and induction of cell death was evident in
      PAM212 cells in vitro. Mechanistically, anti-sEcad administration upregulated an
      array of cell death pathways (i.e., Bad, active caspase-3, and cleaved PARP) and
      inhibited inhibitors of apoptosis (IAP; survivin, livin, etc.), RTKs (HER1, HER2,
      p95HER2, and IGF-1R), MAPK and PI3K/mTOR prosurvival signaling. Interestingly, in
      anti-sEcad mAb-treated tumors and PAM212 cells, this effect was associated with a
      profound increase in membrane, cytosolic, and nuclear levels of PTEN; enhanced
      cytosolic p53; and a decrease in MDM2 levels. Overall, our studies suggest that
      an antibody-based therapy against sEcad may be a novel therapeutic platform for
      cutaneous SCCs by hampering key proto-oncogenes (RTKs, IAPs, and MDM2) and
      activating potent tumor suppressor proteins (PTEN and p53) intricately linked to
      tumor growth and survival.

PMID- 24748655
TI  - Combination of anti-HER3 antibody MM-121/SAR256212 and cetuximab inhibits tumor
      growth in preclinical models of head and neck squamous cell carcinoma.
AB  - The EGFR monoclonal antibody cetuximab is the only approved targeted agent for
      treating head and neck squamous cell carcinoma (HNSCC). Yet resistance to
      cetuximab has hindered its activity in this disease. Intrinsic or compensatory
      HER3 signaling may contribute to cetuximab resistance. To investigate the
      therapeutic benefit of combining MM-121/SAR256212, an anti-HER3 monoclonal
      antibody, with cetuximab in HNSCC, we initially screened 12 HNSCC cell lines for
      total and phosphorylated levels of the four HER receptors. We also investigated
      the combination of MM-121 with cetuximab in preclinical models of HNSCC. Our
      results revealed that HER3 is widely expressed and activated in HNSCC cell lines.
      MM-121 strongly inhibited phosphorylation of HER3 and AKT. When combined with
      cetuximab, MM-121 exerted a more potent antitumor activity through simultaneously
      inhibiting the activation of HER3 and EGFR and consequently the downstream
      PI3K/AKT and ERK pathways in vitro. Both high and low doses of MM-121 in
      combination with cetuximab significantly suppressed tumor growth in xenograft
      models and inhibited activations of HER3, EGFR, AKT, and ERK in vivo. Our work is
      the first report on this new combination in HNSCC and supports the concept that
      HER3 inhibition may play an important role in future therapy of HNSCC. Our
      results open the door for further mechanistic studies to better understand the
      role of HER3 in resistance to EGFR inhibitors in HNSCC.

PMID- 24748656
TI  - Picking the point of inhibition: a comparative review of PI3K/AKT/mTOR pathway
      inhibitors.
AB  - The frequent activation of the PI3K/AKT/mTOR pathway in cancer, and its crucial
      role in cell growth and survival, has made it a much desired target for
      pharmacologic intervention. Following the regulatory approval of the rapamycin
      analogs everolimus and temsirolimus, recent years have seen an explosion in the
      number of phosphoinositide 3-kinase (PI3K) pathway inhibitors under clinical
      investigation. These include: ATP-competitive, dual inhibitors of class I PI3K
      and mTORC1/2; "pan-PI3K" inhibitors, which inhibit all four isoforms of class I
      PI3K (alpha, beta, delta, gamma); isoform-specific inhibitors of the various PI3K
      isoforms; allosteric and catalytic inhibitors of AKT; and ATP-competitive
      inhibitors of mTOR only (and thus mTORC1 and mTORC2). With so many agents in
      development, clinicians are currently faced with a wide array of clinical trials
      investigating a multitude of inhibitors with different mechanisms of action,
      being used both as single agents and in combination with other therapies. Here,
      we provide a review of the literature, with the aim of differentiating the
      genomic contexts in which these various types of inhibitors may potentially have
      superior activity.

PMID- 24748657
TI  - Desensitization of functional u-opioid receptors increases agonist off-rate.
AB  - Desensitization of u-opioid receptors (MORs) develops over 5-15 minutes after the
      application of some, but not all, opioid agonists and lasts for tens of minutes
      after agonist removal. The decrease in function is receptor selective
      (homologous) and could result from 1) a reduction in receptor number or 2) a
      decrease in receptor coupling. The present investigation used photolysis of two
      caged opioid ligands to examine the kinetics of MOR-induced potassium conductance
      before and after MOR desensitization. Photolysis of a caged antagonist,
      carboxynitroveratryl-naloxone (caged naloxone), blocked the current induced by a
      series of agonists, and the time constant of decline was significantly decreased
      after desensitization. The increase in the rate of current decay was not observed
      after partial blockade of receptors with the irreversible antagonist, beta
      chlornaltrexamine (beta-CNA). The time constant of current decay after
      desensitization was never more rapid than 1 second, suggesting an increased
      agonist off-rate rather than an increase in the rate of channel closure
      downstream of the receptor. The rate of G protein-coupled K(+) channel (GIRK)
      current activation was examined using photolysis of a caged agonist,
      carboxynitrobenzyl-tyrosine-[Leu(5)]-enkephalin. After acute desensitization or
      partial irreversible block of MORs with beta-CNA, there was an increase in the
      time it took to reach a peak current. The decrease in the rate of agonist-induced
      GIRK conductance was receptor selective and dependent on receptor number. The
      results indicate that opioid receptor desensitization reduced the number of
      functional receptor and that the remaining active receptors have a reduced
      agonist affinity. 

PMID- 24748658
TI  - The forkhead transcription factor FOXK2 acts as a chromatin targeting factor for
      the BAP1-containing histone deubiquitinase complex.
AB  - There are numerous forkhead transcription factors in mammalian cells but we know
      little about the molecular functions of the majority of these. FOXK2 is a
      ubiquitously expressed family member suggesting an important function across
      multiple cell types. Here, we show that FOXK2 binds to the SIN3A and PR-DUB
      complexes. The PR-DUB complex contains the important tumour suppressor protein,
      the deubiquitinase BAP1. FOXK2 recruits BAP1 to DNA, promotes local histone
      deubiquitination and causes changes in target gene activity. Our results
      therefore provide an important link between BAP1 and the transcription factor
      FOXK2 and demonstrate how BAP1 can be recruited to specific regulatory loci. 

PMID- 24748659
TI  - Genome-wide RNA-binding analysis of the trypanosome U1 snRNP proteins U1C and U1
      70K reveals cis/trans-spliceosomal network.
AB  - Trans-splicing in trypanosomes adds a 39-nucleotide mini-exon from the spliced
      leader (SL) RNA to the 5' end of each protein-coding sequence. On the other hand,
      cis-splicing of the few intron-containing genes requires the U1 small nuclear
      ribonucleoprotein (snRNP) particle. To search for potential new functions of the
      U1 snRNP in Trypanosoma brucei, we applied genome-wide individual-nucleotide
      resolution crosslinking-immunoprecipitation (iCLIP), focusing on the U1 snRNP
      specific proteins U1C and U1-70K. Surprisingly, U1C and U1-70K interact not only
      with the U1, but also with U6 and SL RNAs. In addition, mapping of crosslinks to
      the cis-spliced PAP [poly(A) polymerase] pre-mRNA indicate an active role of
      these proteins in 5' splice site recognition. In sum, our results demonstrate
      that the iCLIP approach provides insight into stable and transient RNA-protein
      contacts within the spliceosomal network. We propose that the U1 snRNP may
      represent an evolutionary link between the cis- and trans-splicing machineries,
      playing a dual role in 5' splice site recognition on the trans-spliceosomal SL
      RNP as well as on pre-mRNA cis-introns. 

PMID- 24748660
TI  - Histone H3 K79 methylation states play distinct roles in UV-induced sister
      chromatid exchange and cell cycle checkpoint arrest in Saccharomyces cerevisiae.
AB  - Histone post-translational modifications have been shown to contribute to DNA
      damage repair. Prior studies have suggested that specific H3K79 methylation
      states play distinct roles in the response to UV-induced DNA damage. To evaluate
      these observations, we examined the effect of altered H3K79 methylation patterns
      on UV-induced G1/S checkpoint response and sister chromatid exchange (SCE). We
      found that the di- and trimethylated states both contribute to activation of the
      G1/S checkpoint to varying degrees, depending on the synchronization method,
      although methylation is not required for checkpoint in response to high levels of
      UV damage. In contrast, UV-induced SCE is largely a product of the trimethylated
      state, which influences the usage of gene conversion versus popout mechanisms.
      Regulation of H3K79 methylation by H2BK123 ubiquitylation is important for both
      checkpoint function and SCE. H3K79 methylation is not required for the repair of
      double-stranded breaks caused by transient HO endonuclease expression, but does
      play a modest role in survival from continuous exposure. The overall results
      provide evidence for the participation of H3K79 methylation in UV-induced
      recombination repair and checkpoint activation, and further indicate that the di-
      and trimethylation states play distinct roles in these DNA damage response
      pathways. 

PMID- 24748662
TI  - Evidence that TSC2 acts as a transcription factor and binds to and represses the
      promoter of Epiregulin.
AB  - The TSC2 gene, mutated in patients with tuberous sclerosis complex (TSC), encodes
      a 200 kDa protein TSC2 (tuberin). The importance of TSC2 in the regulation of
      cell growth and proliferation is irrefutable. TSC2 in complex with TSC1
      negatively regulates the mTOR complex 1 (mTORC1) via RHEB in the PI3K-AKT-mTOR
      pathway and in turn regulates cell proliferation. It shows nuclear as well as
      cytoplasmic localization. However, its nuclear function remains elusive. In order
      to identify the nuclear function of TSC2, a whole-genome expression profiling of
      TSC2 overexpressing cells was performed, and the results showed differential
      regulation of 266 genes. Interestingly, transcription was found to be the most
      populated functional category. EREG (Epiregulin), a member of the epidermal
      growth factor family, was found to be the most downregulated gene in the
      microarray analysis. Previous reports have documented elevated levels of EREG in
      TSC lesions, making its regulatory aspects intriguing. Using the luciferase
      reporter, ChIP and EMSA techniques, we show that TSC2 binds to the EREG promoter
      between -352 bp and -303 bp and negatively regulates its expression. This is the
      first evidence for the role of TSC2 as a transcription factor and of TSC2 binding
      to the promoter of any gene. 

PMID- 24748661
TI  - RalR (a DNase) and RalA (a small RNA) form a type I toxin-antitoxin system in
      Escherichia coli.
AB  - For toxin/antitoxin (TA) systems, no toxin has been identified that functions by
      cleaving DNA. Here, we demonstrate that RalR and RalA of the cryptic prophage rac
      form a type I TA pair in which the antitoxin RNA is a trans-encoded small RNA
      with 16 nucleotides of complementarity to the toxin mRNA. We suggest the newly
      discovered antitoxin gene be named ralA for RalR antitoxin. Toxin RalR functions
      as a non-specific endonuclease that cleaves methylated and unmethylated DNA. The
      RNA chaperone Hfq is required for RalA antitoxin activity and appears to
      stabilize RalA. Also, RalR/RalA is beneficial to the Escherichia coli host for
      responding to the antibiotic fosfomycin. Hence, our results indicate that cryptic
      prophage genes can be functionally divergent from their active phage counterparts
      after integration into the host genome. 

PMID- 24748663
TI  - Efficient chromosomal gene modification with CRISPR/cas9 and PCR-based homologous
      recombination donors in cultured Drosophila cells.
AB  - The ability to edit the genome is essential for many state-of-the-art
      experimental paradigms. Since DNA breaks stimulate repair, they can be exploited
      to target site-specific integration. The clustered, regularly interspaced, short
      palindromic repeats (CRISPR)/cas9 system from Streptococcus pyogenes has been
      harnessed into an efficient and programmable nuclease for eukaryotic cells. We
      thus combined DNA cleavage by cas9, the generation of homologous recombination
      donors by polymerase chain reaction (PCR) and transient depletion of the non
      homologous end joining factor lig4. Using cultured Drosophila melanogaster S2
      cells and the phosphoglycerate kinase gene as a model, we reached targeted
      integration frequencies of up to 50% in drug-selected cell populations. Homology
      arms as short as 29 nt appended to the PCR primer resulted in detectable
      integration, slightly longer extensions are beneficial. We confirmed established
      rules for S. pyogenes cas9 sgRNA design and demonstrate that the complementarity
      region allows length variation and 5'-extensions. This enables generation of U6
      promoter fusion templates by overlap-extension PCR with a standardized protocol.
      We present a series of PCR template vectors for C-terminal protein tagging and
      clonal Drosophila S2 cell lines with stable expression of a myc-tagged cas9
      protein. The system can be used for epitope tagging or reporter gene knock-ins in
      an experimental setup that can in principle be fully automated. 

PMID- 24748664
TI  - Structural and biophysical characterization of Staphylococcus aureus SaMazF shows
      conservation of functional dynamics.
AB  - The Staphylococcus aureus genome contains three toxin-antitoxin modules,
      including one mazEF module, SamazEF. Using an on-column separation protocol we
      are able to obtain large amounts of wild-type SaMazF toxin. The protein is well
      folded and highly resistant against thermal unfolding but aggregates at elevated
      temperatures. Crystallographic and nuclear magnetic resonance (NMR) solution
      studies show a well-defined dimer. Differences in structure and dynamics between
      the X-ray and NMR structural ensembles are found in three loop regions, two of
      which undergo motions that are of functional relevance. The same segments also
      show functionally relevant dynamics in the distantly related CcdB family despite
      divergence of function. NMR chemical shift mapping and analysis of residue
      conservation in the MazF family suggests a conserved mode for the inhibition of
      MazF by MazE. 

PMID- 24748665
TI  - Requirement for Parp-1 and DNA ligases 1 or 3 but not of Xrcc1 in chromosomal
      translocation formation by backup end joining.
AB  - In mammalian cells, ionizing radiation (IR)-induced DNA double-strand breaks
      (DSBs) are repaired in all phases of the cell cycle predominantly by classical,
      DNA-PK-dependent nonhomologous end joining (D-NHEJ). Homologous recombination
      repair (HRR) is functional during the S- and G2-phases, when a sister chromatid
      becomes available. An error-prone, alternative form of end joining, operating as
      backup (B-NHEJ) functions robustly throughout the cell cycle and particularly in
      the G2-phase and is thought to backup predominantly D-NHEJ. Parp-1, DNA-ligases 1
      (Lig1) and 3 (Lig3), and Xrcc1 are implicated in B-NHEJ. Chromosome and chromatid
      translocations are manifestations of erroneous DSB repair and are crucial
      culprits in malignant transformation and IR-induced cell lethality. We analyzed
      shifts in translocation formation deriving from defects in D-NHEJ or HRR in cells
      irradiated in the G2-phase and identify B-NHEJ as the main DSB repair pathway
      backing up both of these defects at the cost of a large increase in translocation
      formation. Our results identify Parp-1 and Lig1 and 3 as factors involved in
      translocation formation and show that Xrcc1 reinforces the function of Lig3 in
      the process without being required for it. Finally, we demonstrate intriguing
      connections between B-NHEJ and DNA end resection in translocation formation and
      show that, as for D-NHEJ and HRR, the function of B-NHEJ facilitates the recovery
      from the G2-checkpoint. These observations advance our understanding of
      chromosome aberration formation and have implications for the mechanism of action
      of Parp inhibitors. 

PMID- 24748666
TI  - The crystal structure of the Split End protein SHARP adds a new layer of
      complexity to proteins containing RNA recognition motifs.
AB  - The Split Ends (SPEN) protein was originally discovered in Drosophila in the late
      1990s. Since then, homologous proteins have been identified in eukaryotic species
      ranging from plants to humans. Every family member contains three predicted RNA
      recognition motifs (RRMs) in the N-terminal region of the protein. We have
      determined the crystal structure of the region of the human SPEN homolog that
      contains these RRMs-the SMRT/HDAC1 Associated Repressor Protein (SHARP), at 2.0 A
      resolution. SHARP is a co-regulator of the nuclear receptors. We demonstrate that
      two of the three RRMs, namely RRM3 and RRM4, interact via a highly conserved
      interface. Furthermore, we show that the RRM3-RRM4 block is the main platform
      mediating the stable association with the H12-H13 substructure found in the
      steroid receptor RNA activator (SRA), a long, non-coding RNA previously shown to
      play a crucial role in nuclear receptor transcriptional regulation. We determine
      that SHARP association with SRA relies on both single- and double-stranded RNA
      sequences. The crystal structure of the SHARP-RRM fragment, together with the
      associated RNA-binding studies, extend the repertoire of nucleic acid binding
      properties of RRM domains suggesting a new hypothesis for a better understanding
      of SPEN protein functions.

PMID- 24748667
TI  - The ESA scenario gets complex: from biosimilar epoetins to activin traps.
AB  - Recombinant human erythropoietin (rhEpo, epoetin) has proved beneficial in
      preventing transfusion-dependent anaemia in patients with chronic kidney disease.
      Apart from copied epoetins distributed in less regulated markets, 'biosimilar'
      epoetins have gained currency in many regions, where they compete with the
      originals and with rhEpo analogues with prolonged survival in circulation
      ('biobetter'). Recombinant erythropoiesis stimulating agents are potent and well
      tolerated. However, their production is costly, and they must be administered by
      the parenteral route. Hence, other anti-anaemia treatments are being evaluated.
      Clinical trials are being performed with stabilizers of the hypoxia-inducible
      transcription factors (HIFs), which increase endogenous Epo production. HIF
      stabilizers are chemical drugs and they are active on oral administration.
      However, there is fear that they may promote tumour growth. Epo mimetic peptides
      have also raised expectations. Yet the prototype peginesatide was recalled after
      just 1 year of its widespread use in the USA because of serious side-effects
      including cases of death. Most recently, clinical trials have been initiated with
      sotatercept, a recombinant soluble activin receptor type 2A IgG-Fc fusion
      protein. Sotatercept binds distinct members of the transforming growth factor
      beta family, thereby preventing the inhibitory action of these factors in
      erythropoiesis. Taken together, rhEpo and its long-acting recombinant analogues
      will likely remain mainstay of anti-anaemia therapies in the near future. 

PMID- 24748668
TI  - ANCA serotype and histopathological classification for the prediction of renal
      outcome in ANCA-associated glomerulonephritis.
AB  - BACKGROUND: The phenotype of renal involvement in anti-neutrophil cytoplasmic
      antibodies (ANCA) vasculitis has a major influence on survival, and histological
      subgrouping of diagnostic renal biopsies has been proposed to aid in the
      prediction of renal outcome. We aimed to validate this histological subgrouping
      and to investigate the additional value of ANCA serotype in the prediction of
      renal outcome. METHODS: Data were retrospectively collected from the time of
      diagnosis by systematic review of medical records from 136 patients with renal
      biopsies recruited to cohorts from the UK and Spain, over 15 years. The end
      point, renal survival, was the composite of end-stage renal disease (ESRD) or
      death from any cause. The occurrence of ESRD, Stage 4 Kidney Disease Outcomes
      Quality Initiative-Chronic Kidney Disease, was assessed separately, in order to
      establish a severity index risk of chronic kidney disease. RESULTS: Renal
      survival at 5 years was 96% in the focal, 86% in the crescentic, 81% in the mixed
      and 61% in the sclerotic subgroups (P = 0.03). Myeloperoxidase (MPO)-ANCA was
      associated with more severe disease when compared with PR3-ANCA, as demonstrated
      by a lower frequency of focal and higher frequency of sclerotic subgroups, by
      more advanced interstitial fibrotic change and by lower glomerular filtration
      rate at diagnosis and worse renal function at 1 and 2 years. CONCLUSIONS: We have
      confirmed the predictive value for renal survival of the ANCA vasculitis
      histology classification in a multi-centre study. We found a worse renal outcome
      in patients with tubulointerstitial fibrosis and atrophy. MPO-ANCA positive
      patients had a worse renal prognosis due to more severe glomerular injury. These
      results contribute to patient stratification in renal vasculitis for therapeutic,
      epidemiological and basic research.

PMID- 24748669
TI  - beta-Amyloidosis and neurodegeneration in Alzheimer disease: who's on first?

PMID- 24748670
TI  - Brain reserve and cognitive reserve protect against cognitive decline over 4.5
      years in MS.
AB  - OBJECTIVE: Based on the theories of brain reserve and cognitive reserve, we
      investigated whether larger maximal lifetime brain growth (MLBG) and/or greater
      lifetime intellectual enrichment protect against cognitive decline over time.
      METHODS: Forty patients with multiple sclerosis (MS) underwent baseline and 4.5
      year follow-up evaluations of cognitive efficiency (Symbol Digit Modalities Test,
      Paced Auditory Serial Addition Task) and memory (Selective Reminding Test,
      Spatial Recall Test). Baseline and follow-up MRIs quantified disease progression:
      percentage brain volume change (cerebral atrophy), percentage change in T2 lesion
      volume. MLBG (brain reserve) was estimated with intracranial volume; intellectual
      enrichment (cognitive reserve) was estimated with vocabulary. We performed
      repeated-measures analyses of covariance to investigate whether larger MLBG
      and/or greater intellectual enrichment moderate/attenuate cognitive decline over
      time, controlling for disease progression. RESULTS: Patients with MS declined in
      cognitive efficiency and memory (p < 0.001). MLBG moderated decline in cognitive
      efficiency (p = 0.031, etap (2) = 0.122), with larger MLBG protecting against
      decline. MLBG did not moderate memory decline (p = 0.234, etap (2) = 0.039).
      Intellectual enrichment moderated decline in cognitive efficiency (p = 0.031,
      etap (2) = 0.126) and memory (p = 0.037, etap (2) = 0.115), with greater
      intellectual enrichment protecting against decline. MS disease progression was
      more negatively associated with change in cognitive efficiency and memory among
      patients with lower vs higher MLBG and intellectual enrichment. CONCLUSION: We
      provide longitudinal support for theories of brain reserve and cognitive reserve
      in MS. Larger MLBG protects against decline in cognitive efficiency, and greater
      intellectual enrichment protects against decline in cognitive efficiency and
      memory. Consideration of these protective factors should improve prediction of
      future cognitive decline in patients with MS.

PMID- 24748671
TI  - CSF Abeta42 predicts early-onset dementia in Parkinson disease.
AB  - OBJECTIVE: To test in vivo the proposal from clinicopathologic studies that beta
      amyloid (Abeta) pathology shortens the time to dementia in Parkinson disease
      (PD), and to explore the utility of CSF Abeta and related measures as early
      prognostic biomarkers of dementia in an incident PD cohort. METHODS: We assessed
      a population-based incident cohort of 104 patients with PD who underwent lumbar
      puncture at diagnosis. We analyzed CSF concentrations of Abeta42, Abeta40, and
      Abeta38 using a multiplexed immunoassay with electrochemiluminescence (ECL)
      detection and levels of Abeta42, total tau, and phosphorylated tau using ELISA.
      Patients were followed prospectively for 5 years. Dementia was diagnosed
      according to published criteria. RESULTS: CSF levels of Abeta42 were
      significantly decreased in patients who developed dementia (n = 20, 19.2%)
      compared to those who did not (n = 84, 80.8%), as measured by ECL (-33%, p =
      0.006) as well as ELISA (-36%, p < 0.001). No differences were observed for other
      markers. Low Abeta42 values predicted a substantially increased risk for
      subsequent dementia at high sensitivity (>= 85%), with hazard ratios of 9.9 (95%
      confidence interval 2.3-43.5, p = 0.002) for Abeta42ECL <376 pg/mL and 7.6 (2.2
      26.4, p = 0.001) for Abeta42ELISA <443 pg/mL, after adjustment for baseline age
      and PD-mild cognitive impairment (MCI) status. Abeta42 reductions tended to
      precede the onset of PD-MCI that progressed to dementia. CONCLUSIONS: These in
      vivo data support the role of Abeta pathology in the etiology and highlight the
      potential utility of CSF Abeta42 as an early prognostic biomarker of dementia
      associated with PD.

PMID- 24748672
TI  - Long-term effects of amyloid, hypometabolism, and atrophy on neuropsychological
      functions.
AB  - OBJECTIVE: To assess how amyloid deposition, glucose hypometabolism, and cerebral
      atrophy affect neuropsychological performance in patients with Alzheimer disease
      (AD) dementia, patients with mild cognitive impairment (MCI), and controls over
      time. METHODS: A total of 41 patients with AD dementia, 28 patients with MCI, and
      19 controls underwent [(11)C]-Pittsburgh compound B ((11)C-PiB) and [(18)F]-2
      fluoro-2-deoxy-d-glucose ((18)F-FDG)-PET and MRI scans at baseline. We extracted
      global binding potential for (11)C-PiB, the number of abnormal voxels for (18)F
      FDG, and gray matter volumes using SIENAX for MRI as measures of amyloid,
      hypometabolism, and atrophy. In addition, repeat neuropsychological testing was
      performed, including memory, attention, language, and executive tasks (mean
      follow-up 2.2 +/- 0.7 years). Cross-sectional and longitudinal relationships
      between imaging markers and cognition were assessed using linear mixed models,
      including terms for the imaging markers, time, sex, age, diagnosis, and
      interactions for imaging marker * time and imaging marker * time * diagnosis.
      RESULTS: Linear mixed models showed that baseline hypometabolism and atrophy were
      associated with poorer baseline performance on attention and executive functions
      (p < 0.05), whereas amyloid was not related to baseline cognition. Hypometabolism
      and amyloid were strongly associated with longitudinal decline in essentially all
      cognitive domains (pinteraction < 0.05), whereas atrophy was related specifically
      to future decline in Mini-Mental State Examination and memory (pinteraction <
      0.05). CONCLUSION: Glucose hypometabolism and brain atrophy were associated with
      concurrent cognitive function, whereas brain amyloid was not. Amyloid deposition
      and glucose hypometabolism were predictors for decline of a wide variety of
      cognitive functions, while brain atrophy specifically predicted memory
      deterioration.

PMID- 24748673
TI  - beta-Amyloid in CSF: a window into Parkinson disease dementia.

PMID- 24748677
TI  - Hsp90 interaction with INrf2(Keap1) mediates stress-induced Nrf2 activation.

PMID- 24748674
TI  - Amyloid and APOE epsilon4 interact to influence short-term decline in preclinical
      Alzheimer disease.
AB  - OBJECTIVE: To examine whether beta-amyloid (Abeta) and APOE epsilon4 status
      independently contribute or interact to influence longitudinal cognitive decline
      in clinically normal older individuals (CN). METHODS: Data from 490 CNs were
      aggregated across 3 observational cohort studies (Harvard Aging Brain Study,
      Alzheimer's Disease Neuroimaging Initiative, and Australian Imaging Biomarkers
      and Lifestyle Study of Ageing; median age = 75.0 years, 255 female), and the
      contributions of APOE epsilon4 and Abeta on longitudinal change over a median of
      1.49 years were examined. Cognitive decline was assessed with the Mini-Mental
      State Examination (MMSE) and Logical Memory (immediate and delayed recall
      scores). RESULTS: High Abeta participants were more likely to be APOE epsilon4+
      than low Abeta participants. CNs who were both high Abeta and APOE epsilon4+
      showed greater decline in Logical Memory immediate recall (p < 0.087), Logical
      Memory delayed recall (p < 0.024), and MMSE (p < 0.034) compared to all other
      groups (low Abeta/APOE epsilon4-, low Abeta/APOE epsilon4+, and high Abeta/APOE
      epsilon4-). No other pairwise contrast was significant for any cognitive measure.
      CONCLUSIONS: Clinically normal individuals who are APOE epsilon4+ and have high
      Abeta showed the highest cognitive decline. These results suggest that Abeta and
      APOE epsilon4 are not redundant contributors of decline in aging but rather
      interact to promote decline during the short follow-up period examined in this
      study. Longer follow-up periods will be essential to fully elucidate the
      influence of Alzheimer disease risk factors on cognitive decline in aging.

PMID- 24748681
TI  - Developmental Climate: A Cross-level Analysis of Voluntary Turnover and Job
      Performance.
AB  - This research investigates the influence of shared perceptions of developmental
      climate on individual-level perceptions of organizational commitment, engagement,
      and perceived competence, and whether these attitudes mediate the relationship
      between developmental climate and both individual voluntary turnover and
      supervisor-rated job performance. Survey data were collected from 361 intact
      employee-supervisory mentoring dyads and matched with employee turnover data
      collected one year later to test the proposed framework using multilevel modeling
      techniques. As expected, shared perceptions of developmental climate were
      significantly and positively related to all three individual work attitudes. In
      addition, both organizational commitment and perceived competence were
      significant mediators of the positive relationship between shared perceptions of
      developmental climate and voluntary turnover, as well as shared perceptions of
      developmental climate and supervisor-rated job performance. By contrast, no
      significant mediating effects were found for engagement. Theoretical
      implications, limitations, and future research are discussed.

PMID- 24748682
TI  - Selection on Moral Hazard in Health Insurance.
AB  - We use employee-level panel data from a single firm to explore the possibility
      that individuals may select insurance coverage in part based on their anticipated
      behavioral ("moral hazard") response to insurance, a phenomenon we label
      "selection on moral hazard." Using a model of plan choice and medical
      utilization, we present evidence of heterogeneous moral hazard as well as
      selection on it, and explore some of its implications. For example, we show that,
      at least in our context, abstracting from selection on moral hazard could lead to
      over-estimates of the spending reduction associated with introducing a high
      deductible health insurance option.

PMID- 24748683
TI  - Environmental and management influences on temporal variability of near saturated
      soil hydraulic properties.
AB  - Structural porosity is a decisive property for soil productivity and soil
      environmental functions. Hydraulic properties in the structural range vary over
      time in response to management and environmental influences. Although this is
      widely recognized, there are few field studies that determine dominant driving
      forces underlying hydraulic property dynamics. During a three year field
      experiment we measured temporal variability of soil hydraulic properties by
      tension infiltrometry. Soil properties were characterized by hydraulic
      conductivity, effective macroporosity and Kosugi's lognormal pore size
      distribution model. Management related influences comprised three soil cover
      treatment (mustard and rye vs. fallow) and an initial mechanical soil disturbance
      with a rotary harrow. Environmental driving forces were derived from
      meteorological and soil moisture data. Soil hydraulic parameters varied over time
      by around one order of magnitude. The coefficient of variation of soil hydraulic
      conductivity K(h) decreased from 69.5% at saturation to 42.1% in the more
      unsaturated range (- 10 cm pressure head). A slight increase in the Kosugi
      parameter showing pore heterogeneity was observed under the rye cover crop,
      reflecting an enhanced structural porosity. The other hydraulic parameters were
      not significantly influenced by the soil cover treatments. Seedbed preparation
      with a rotary harrow resulted in a fourfold increase in macroporosity and
      hydraulic conductivity next to saturation, and homogenized the pore radius
      distribution. Re-consolidation after mechanical loosening lasted over 18 months
      until the soil returned to its initial state. The post-tillage trend of soil
      settlement could be approximated by an exponential decay function. Among
      environmental factors, wetting-drying cycles were identified as dominant driving
      force explaining short term hydraulic property changes within the season (r2 =
      0.43 to 0.59). Our results suggested that beside considering average management
      induced changes in soil properties (e.g. cover crop introduction), a dynamic
      approach to hydrological modeling is required to capture over-seasonal (tillage
      driven) and short term (environmental driven) variability in hydraulic
      parameters.

PMID- 24748684
TI  - Normative Foundations of Global Health Law.

PMID- 24748685
TI  - High-order spectral/hp element discretisation for reaction-diffusion problems on
      surfaces: Application to cardiac electrophysiology.
AB  - We present a numerical discretisation of an embedded two-dimensional manifold
      using high-order continuous Galerkin spectral/hp elements, which provide
      exponential convergence of the solution with increasing polynomial order, while
      retaining geometric flexibility in the representation of the domain. Our work is
      motivated by applications in cardiac electrophysiology where sharp gradients in
      the solution benefit from the high-order discretisation, while the computational
      cost of anatomically-realistic models can be significantly reduced through the
      surface representation and use of high-order methods. We describe and validate
      our discretisation and provide a demonstration of its application to modelling
      electrochemical propagation across a human left atrium.

PMID- 24748686
TI  - A Peer-Led High School Transition Program Increases Graduation Rates Among Latino
      Males.
AB  - The present study investigated the impact of a manualized high school transition
      program, the Peer Group Connection (PGC) program, on the graduation rate at a low
      income, Mid-Atlantic high school. The program utilized twelfth grade student peer
      leaders to create a supportive environment for incoming ninth grade students.
      Results of a randomized control trial demonstrated that male students who
      participated in the program during ninth grade were significantly more likely to
      graduate from high school within four years than male students in the control
      group (81% versus 63%). Findings suggest that peers can be effective in
      delivering a school-based, social emotional learning intervention and that it is
      possible to intervene in the ninth grade to influence the probability of high
      school graduation.

PMID- 24748687
TI  - Single event time series analysis in a binary karst catchment evaluated using a
      groundwater model (Lurbach system, Austria).
AB  - The Lurbach karst system (Styria, Austria) is drained by two major springs and
      replenished by both autogenic recharge from the karst massif itself and a sinking
      stream that originates in low permeable schists (allogenic recharge). Detailed
      data from two events recorded during a tracer experiment in 2008 demonstrate that
      an overflow from one of the sub-catchments to the other is activated if the
      discharge of the main spring exceeds a certain threshold. Time series analysis
      (autocorrelation and cross-correlation) was applied to examine to what extent the
      various available methods support the identification of the transient inter
      catchment flow observed in this binary karst system. As inter-catchment flow is
      found to be intermittent, the evaluation was focused on single events. In order
      to support the interpretation of the results from the time series analysis a
      simplified groundwater flow model was built using MODFLOW. The groundwater model
      is based on the current conceptual understanding of the karst system and
      represents a synthetic karst aquifer for which the same methods were applied.
      Using the wetting capability package of MODFLOW, the model simulated an overflow
      similar to what has been observed during the tracer experiment. Various
      intensities of allogenic recharge were employed to generate synthetic discharge
      data for the time series analysis. In addition, geometric and hydraulic
      properties of the karst system were varied in several model scenarios. This
      approach helps to identify effects of allogenic recharge and aquifer properties
      in the results from the time series analysis. Comparing the results from the time
      series analysis of the observed data with those of the synthetic data a good
      agreement was found. For instance, the cross-correlograms show similar patterns
      with respect to time lags and maximum cross-correlation coefficients if
      appropriate hydraulic parameters are assigned to the groundwater model. The
      comparable behaviors of the real and the synthetic system allow to deduce that
      similar aquifer properties are relevant in both systems. In particular, the
      heterogeneity of aquifer parameters appears to be a controlling factor. Moreover,
      the location of the overflow connecting the sub-catchments of the two springs is
      found to be of primary importance, regarding the occurrence of inter-catchment
      flow. This further supports our current understanding of an overflow zone located
      in the upper part of the Lurbach karst aquifer. Thus, time series analysis of
      single events can potentially be used to characterize transient inter-catchment
      flow behavior of karst systems.

PMID- 24748688
TI  - Dearth by a Thousand Cuts? Accounting for Gender Differences in Top-Ranked
      Publication Rates in Social Psychology.
AB  - Publication in the Journal of Personality and Social Psychology, a flagship
      indicator of scientific prestige, shows dramatic gender disparities. A
      bibliometric analysis included yoked-control authors matched for Ph.D. prestige
      and cohort. Though women publish less, at slower annual rates, they are more
      cited in handbooks and textbooks per JPSP-article-published. No gender
      differences emerged on variables reflecting differential qualifications. Many
      factors explain gender discrepancy in productivity. Among top publishers, per
      year rate and first authorship especially differ by gender; rate uniquely
      predicts top-male productivity, whereas career-length uniquely predicts top
      female productivity. Among men, across top-publishers and controls, productivity
      correlates uniquely with editorial negotiating and being married. For women, no
      personal variables predict productivity. A separate inquiry shows tiny gender
      differences in acceptance rates per JPSP article submitted; discrimination would
      be a small-but-plausible contributor, absent independent indicators of manuscript
      quality. Recent productivity rates mirror earlier gender disparities, suggesting
      gender gaps will continue.

PMID- 24748680
TI  - Emergent complexity of the cytoskeleton: from single filaments to tissue.
AB  - Despite their overwhelming complexity, living cells display a high degree of
      internal mechanical and functional organization which can largely be attributed
      to the intracellular biopolymer scaffold, the cytoskeleton. Being a very complex
      system far from thermodynamic equilibrium, the cytoskeleton's ability to organize
      is at the same time challenging and fascinating. The extensive amounts of
      frequently interacting cellular building blocks and their inherent
      multifunctionality permits highly adaptive behavior and obstructs a purely
      reductionist approach. Nevertheless (and despite the field's relative novelty),
      the physics approach has already proved to be extremely successful in revealing
      very fundamental concepts of cytoskeleton organization and behavior. This review
      aims at introducing the physics of the cytoskeleton ranging from single
      biopolymer filaments to multicellular organisms. Throughout this wide range of
      phenomena, the focus is set on the intertwined nature of the different physical
      scales (levels of complexity) that give rise to numerous emergent properties by
      means of self-organization or self-assembly.

PMID- 24748689
TI  - Breaking Up is Hard to Do, Unless Everyone Else is Doing it Too: Social Network
      Effects on Divorce in a Longitudinal Sample.
AB  - Divorce represents the dissolution of a social tie, but it is also possible that
      attitudes about divorce flow across social ties. To explore how social networks
      influence divorce and vice versa, we exploit a longitudinal data set from the
      long-running Framingham Heart Study. The results suggest that divorce can spread
      between friends. Clusters of divorces extend to two degrees of separation in the
      network. Popular people are less likely to get divorced, divorcees have denser
      social networks, and they are much more likely to remarry other divorcees.
      Interestingly, the presence of children does not influence the likelihood of
      divorce, but each child reduces the susceptibility to being influenced by peers
      who get divorced. Overall, the results suggest that attending to the health of
      one's friends' marriages may serve to support and enhance the durability of one's
      own relationship, and that, from a policy perspective, divorce should be
      understood as a collective phenomenon that extends beyond those directly
      affected.

PMID- 24748690
TI  - Oxygen on an Fe monolayer on W(110): From chemisorption to oxidation.
AB  - The adsorption of oxygen on a pseudomorphic iron monolayer deposited on a W(110)
      surface was studied experimentally and theoretically. Standard surface
      characterization methods, such as Auger electron spectroscopy and low energy
      electron diffraction, and specific nuclear methods, such as conversion electron
      Mossbauer spectroscopy (CEMS) and nuclear resonant scattering of synchrotron
      radiation, combined with theoretical calculations based on the density functional
      theory allowed us to determine the structure of the oxygen adsorbate and the
      electronic properties of iron atoms with different oxygen coordinations. The
      oxygen-(3 * 2) structure on the iron monolayer was recognized and was interpreted
      to be a state with oxygen chemisorbed on the non-reconstructed surface with
      modest electron transfer from iron to oxygen. A transition from chemisorbed
      oxygen to the onset of Fe-oxidation is revealed by distinct changes in the CEMS
      spectra.

PMID- 24748691
TI  - Stoichiometry-driven switching between surface reconstructions on SrTiO3(001).
AB  - Controlling the surface structure on the atomic scale is a major difficulty for
      most transition metal oxides; this is especially true for the ternary
      perovskites. The influence of surface stoichiometry on the atomic structure of
      the SrTiO3(001) surface was examined with scanning tunneling microscopy, low
      energy electron diffraction, low-energy He+ ion scattering (LEIS), and X-ray
      photoelectron spectroscopy (XPS). Vapor deposition of 0.8 monolayer (ML)
      strontium and 0.3 ML titanium, with subsequent annealing to 850  degrees C in 4 *
      10- 6 mbar O2, reversibly switches the surface between c(4 * 2) and (2 * 2)
      reconstructions, respectively. The combination of LEIS and XPS shows a different
      stoichiometry that is confined to the top layer. Geometric models for these
      reconstructions need to take into account these different surface compositions.

PMID- 24748692
TI  - Using Marital Attitudes in Late Adolescence to Predict Later Union Transitions.
AB  - Using a sample of 982 late adolescents and tracking them throughout young
      adulthood, this study investigated if marital attitudes held during the last year
      of high school were predictive of union transitions to both cohabitation and
      marriage during young adulthood. Results using both logistic regression and
      discrete event history models found that marital attitudes did not have
      significant associations with the transition to cohabitation but did
      significantly predict the probability of transitioning to marriage during young
      adulthood. Specifically, having a younger expected age of marriage and placing
      more importance on marriage at the end of adolescence was associated with an
      increased likelihood of transitioning to marriage earlier than other young
      adults.

PMID- 24748693
TI  - On standard conjugate families for natural exponential families with bounded
      natural parameter space.
AB  - Diaconis and Ylvisaker (1979) give necessary conditions for conjugate priors for
      distributions from the natural exponential family to be proper as well as to have
      the property of linear posterior expectation of the mean parameter of the family.
      Their conditions for propriety and linear posterior expectation are also
      sufficient if the natural parameter space is equal to the set of all [Formula:
      see text]-dimensional real numbers. In this paper their results are extended to
      characterize when conjugate priors are proper if the natural parameter space is
      bounded. For the special case where the natural exponential family is through a
      spherical probability distribution  [Formula: see text], we show that the proper
      conjugate priors can be characterized by the behavior of the moment generating
      function of [Formula: see text] at the boundary of the natural parameter space,
      or the second-order tail behavior of [Formula: see text]. In addition, we show
      that if these families are non-regular, then linear posterior expectation never
      holds. The results for this special case are also extended to natural exponential
      families through elliptical probability distributions.

PMID- 24748694
TI  - An infrastructure for accurate characterization of single-event transients in
      digital circuits.
AB  - We present the architecture and a detailed pre-fabrication analysis of a digital
      measurement ASIC facilitating long-term irradiation experiments of basic
      asynchronous circuits, which also demonstrates the suitability of the general
      approach for obtaining accurate radiation failure models developed in our FATAL
      project. Our ASIC design combines radiation targets like Muller C-elements and
      elastic pipelines as well as standard combinational gates and flip-flops with an
      elaborate on-chip measurement infrastructure. Major architectural challenges
      result from the fact that the latter must operate reliably under the same
      radiation conditions the target circuits are exposed to, without wasting precious
      die area for a rad-hard design. A measurement architecture based on multiple non
      rad-hard counters is used, which we show to be resilient against double faults,
      as well as many triple and even higher-multiplicity faults. The design evaluation
      is done by means of comprehensive fault injection experiments, which are based on
      detailed Spice models of the target circuits in conjunction with a standard
      double-exponential current injection model for single-event transients (SET). To
      be as accurate as possible, the parameters of this current model have been
      aligned with results obtained from 3D device simulation models, which have in
      turn been validated and calibrated using micro-beam radiation experiments at the
      GSI in Darmstadt, Germany. For the latter, target circuits instrumented with high
      speed sense amplifiers have been used for analog SET recording. Together with a
      probabilistic analysis of the sustainable particle flow rates, based on a
      detailed area analysis and experimental cross-section data, we can conclude that
      the proposed architecture will indeed sustain significant target hit rates,
      without exceeding the resilience bound of the measurement infrastructure.

PMID- 24748695
TI  - Development of face scanning for own- and other-race faces in infancy.
AB  - The present study investigated whether infants visually scan own- and other-race
      faces differently as well as how these differences in face scanning develop with
      age. A multi-method approach was used to analyze the eye-tracking data of 6- and
      9-month-old Caucasian infants scanning dynamically displayed own- and other-race
      faces. We found that 6-month-olds showed differential fixation, fixating
      significantly more on the left eye and mouth of own-race faces, but more on the
      nose of other-race faces. Infants at 9 months of age fixated more on the eyes of
      own-race faces, but more on the mouth of other-race faces. A scan path analysis
      revealed that infants shifted their attention between the eyes of the own-race
      faces significantly more frequently than for other-race faces. Overall, younger
      and older infants responded differentially to own- versus other-race faces not
      only in the absolute amount of time spent fixating specific features, but also on
      their fixation shifts between features.

PMID- 24748696
TI  - A set-covering based heuristic algorithm for the periodic vehicle routing
      problem.
AB  - We present a hybrid optimization algorithm for mixed-integer linear programming,
      embedding both heuristic and exact components. In order to validate it we use the
      periodic vehicle routing problem (PVRP) as a case study. This problem consists of
      determining a set of minimum cost routes for each day of a given planning
      horizon, with the constraints that each customer must be visited a required
      number of times (chosen among a set of valid day combinations), must receive
      every time the required quantity of product, and that the number of routes per
      day (each respecting the capacity of the vehicle) does not exceed the total
      number of available vehicles. This is a generalization of the well-known vehicle
      routing problem (VRP). Our algorithm is based on the linear programming (LP)
      relaxation of a set-covering-like integer linear programming formulation of the
      problem, with additional constraints. The LP-relaxation is solved by column
      generation, where columns are generated heuristically by an iterated local search
      algorithm. The whole solution method takes advantage of the LP-solution and
      applies techniques of fixing and releasing of the columns as a local search,
      making use of a tabu list to avoid cycling. We show the results of the proposed
      algorithm on benchmark instances from the literature and compare them to the
      state-of-the-art algorithms, showing the effectiveness of our approach in
      producing good quality solutions. In addition, we report the results on realistic
      instances of the PVRP introduced in Pacheco et al. (2011)  [24] and on benchmark
      instances of the periodic traveling salesman problem (PTSP), showing the efficacy
      of the proposed algorithm on these as well. Finally, we report the new best known
      solutions found for all the tested problems.

PMID- 24748697
TI  - Ethylene glycol revisited: Molecular dynamics simulations and visualization of
      the liquid and its hydrogen-bond network.
AB  - Molecular dynamics simulations of liquid ethylene glycol described by the OPLS-AA
      force field were performed to gain insight into its hydrogen-bond structure. We
      use the population correlation function as a statistical measure for the hydrogen
      bond lifetime. In an attempt to understand the complicated hydrogen-bonding, we
      developed new molecular visualization tools within the Vish Visualization shell
      and used it to visualize the life of each individual hydrogen-bond. With this
      tool hydrogen-bond formation and breaking as well as clustering and chain
      formation in hydrogen-bonded liquids can be observed directly. Liquid ethylene
      glycol at room temperature does not show significant clustering or chain
      building. The hydrogen-bonds break often due to the rotational and vibrational
      motions of the molecules leading to an H-bond half-life time of approximately 1.5
      ps. However, most of the H-bonds are reformed again so that after 50 ps only 40%
      of these H-bonds are irreversibly broken due to diffusional motion. This hydrogen
      bond half-life time due to diffusional motion is 80.3 ps. The work was preceded
      by a careful check of various OPLS-based force fields used in the literature. It
      was found that they lead to quite different angular and H-bond distributions.

PMID- 24748698
TI  - Avoiding a bad apple: Insect pollination enhances fruit quality and economic
      value.
AB  - Insect pollination is important for food production globally and apples are one
      of the major fruit crops which are reliant on this ecosystem service. It is
      fundamentally important that the full range of benefits of insect pollination to
      crop production are understood, if the costs of interventions aiming to enhance
      pollination are to be compared against the costs of the interventions themselves.
      Most previous studies have simply assessed the benefits of pollination to crop
      yield and ignored quality benefits and how these translate through to economic
      values. In the present study we examine the influence of insect pollination
      services on farmgate output of two important UK apple varieties; Gala and Cox.
      Using field experiments, we quantify the influence of insect pollination on yield
      and importantly quality and whether either may be limited by sub-optimal insect
      pollination. Using an expanded bioeconomic model we value insect pollination to
      UK apple production and establish the potential for improvement through
      pollination service management. We show that insects are essential in the
      production of both varieties of apple in the UK and contribute a total of L36.7
      million per annum, over L6 million more than the value calculated using more
      conventional dependence ratio methods. Insect pollination not only affects the
      quantity of production but can also have marked impacts on the quality of apples,
      influencing size, shape and effecting their classification for market. These
      effects are variety specific however. Due to the influence of pollination on both
      yield and quality in Gala, there is potential for insect pollination services to
      improve UK output by up to L5.7 million per annum. Our research shows that
      continued pollinator decline could have serious financial implications for the
      apple industry but there is considerable scope through management of wild
      pollinators or using managed pollinator augmentation, to improve the quality of
      production. Furthermore, we show that it is critically important to consider all
      production parameters including quality, varietal differences and management
      costs when valuing the pollination service of any crop so investment in
      pollinator management can be proportional to its contribution.

PMID- 24748699
TI  - Increased efficiency of direct nanoimprinting on planar and curved bulk titanium
      through surface modification.
AB  - In this work the direct transfer of nanopatterns into titanium is demonstrated.
      The nanofeatures are imprinted at room temperature using diamond stamps in a
      single step. We also show that the imprint properties of the titanium surface can
      be altered by anodisation yielding a significant reduction in the required
      imprint force for pattern transfer. The anodisation process is also utilised for
      curved titanium surfaces where a reduced imprint force is preferable to avoid
      sample deformation and damage. We finally demonstrate that our process can be
      applied directly to titanium rods.

PMID- 24748700
TI  - Avoiding bias due to perfect prediction in multiple imputation of incomplete
      categorical variables.
AB  - Multiple imputation is a popular way to handle missing data. Automated procedures
      are widely available in standard software. However, such automated procedures may
      hide many assumptions and possible difficulties from the view of the data
      analyst. Imputation procedures such as monotone imputation and imputation by
      chained equations often involve the fitting of a regression model for a
      categorical outcome. If perfect prediction occurs in such a model, then automated
      procedures may give severely biased results. This is a problem in some standard
      software, but it may be avoided by bootstrap methods, penalised regression
      methods, or a new augmentation procedure.

PMID- 24748701
TI  - A novel ToF-SIMS operation mode for sub 100 nm lateral resolution: Application
      and performance.
AB  - A novel operation mode for time of flight-secondary ion mass spectrometry (ToF
      SIMS) is described for a TOF.SIMS 5 instrument with a Bi-ion gun. It features sub
      100 nm lateral resolution, adjustable primary ion currents and the possibility to
      measure with high lateral resolution as well as high mass resolution. The
      adjustment and performance of the novel operation mode are described and compared
      to established ToF-SIMS operation modes. Several examples of application
      featuring novel scientific results show the capabilities of the operation mode in
      terms of lateral resolution, accuracy of isotope analysis of oxygen, and
      combination of high lateral and mass resolution. The relationship between high
      lateral resolution and operation of SIMS in static mode is discussed.

PMID- 24748702
TI  - Denudation of the continental shelf between Britain and France at the glacial
      interglacial timescale.
AB  - The erosional morphology preserved at the sea bed in the eastern English Channel
      dominantly records denudation of the continental shelf by fluvial processes over
      multiple glacial-interglacial sea-level cycles rather than by catastrophic
      flooding through the Straits of Dover during the mid-Quaternary. Here, through
      the integration of multibeam bathymetry and shallow sub-bottom 2D seismic
      reflection profiles calibrated with vibrocore records, the first stratigraphic
      model of erosion and deposition on the eastern English Channel continental shelf
      is presented. Published Optical Stimulated Luminescence (OSL) and 14C ages were
      used to chronometrically constrain the stratigraphy and allow correlation of the
      continental shelf record with major climatic/sea-level periods. Five major
      erosion surfaces overlain by discrete sediment packages have been identified. The
      continental shelf in the eastern English Channel preserves a record of processes
      operating from Marine Isotope Stage (MIS) 6 to MIS 1. Planar and channelised
      erosion surfaces were formed by fluvial incision during lowstands or relative sea
      level fall. The depth and lateral extent of incision was partly conditioned by
      underlying geology (rock type and tectonic structure), climatic conditions and
      changes in water and sediment discharge coupled to ice sheet dynamics and the
      drainage configuration of major rivers in Northwest Europe. Evidence for major
      erosion during or prior to MIS 6 is preserved. Fluvial sediments of MIS 2 age
      were identified within the Northern Palaeovalley, providing insights into the
      scale of erosion by normal fluvial regimes. Seismic and sedimentary facies
      indicate that deposition predominantly occurred during transgression when
      accommodation was created in palaeovalleys to allow discrete sediment bodies to
      form. Sediment reworking over multiple sea-level cycles (Saalian-Eemian-early
      Weichselian) by fluvial, coastal and marine processes created a multi-lateral,
      multi-storey succession of palaeovalley-fills that are preserved as a strath
      terrace. The data presented here reveal a composite erosional and depositional
      record that has undergone a high degree of reworking over multiple sea-level
      cycles leading to the preferential preservation of sediments associated with the
      most recent glacial-interglacial period.

PMID- 24748703
TI  - Multi-scale curvature for automated identification of glaciated mountain
      landscapes.
AB  - Erosion by glacial and fluvial processes shapes mountain landscapes in a long
      recognized and characteristic way. Upland valleys incised by fluvial processes
      typically have a V-shaped cross-section with uniform and moderately steep slopes,
      whereas glacial valleys tend to have a U-shaped profile with a changing slope
      gradient. We present a novel regional approach to automatically differentiate
      between fluvial and glacial mountain landscapes based on the relation of multi
      scale curvature and drainage area. Sample catchments are delineated and multiple
      moving window sizes are used to calculate per-cell curvature over a variety of
      scales ranging from the vicinity of the flow path at the valley bottom to
      catchment sections fully including valley sides. Single-scale curvature can take
      similar values for glaciated and non-glaciated catchments but a comparison of
      multi-scale curvature leads to different results according to the typical cross
      sectional shapes. To adapt these differences for automated classification of
      mountain landscapes into areas with V- and U-shaped valleys, curvature values are
      correlated with drainage area and a new and simple morphometric parameter, the
      Difference of Minimum Curvature (DMC), is developed. At three study sites in the
      western United States the DMC thresholds determined from catchment analysis are
      used to automatically identify 5 * 5 km quadrats of glaciated and non-glaciated
      landscapes and the distinctions are validated by field-based geological and
      geomorphological maps. Our results demonstrate that DMC is a good predictor of
      glacial imprint, allowing automated delineation of glacially and fluvially
      incised mountain landscapes.

PMID- 24748704
TI  - The Challenge and Opportunity of Parental Involvement in Juvenile Justice
      Services.
AB  - The active involvement of parents - whether as recipients, extenders, or managers
      of services - during their youth's experience with the juvenile justice system is
      widely assumed to be crucial. Parents and family advocacy groups note persisting
      concerns with the degree to which successful parental involvement is achieved.
      Justice system providers are highly motivated and actively working to make
      improvements. These coalescing interests provide a strong motivation for
      innovation and improvement regarding family involvement, but the likely success
      of these efforts is severely limited by the absence of any detailed definition of
      parental involvement or validated measure of this construct. Determining whether
      and how parental involvement works in juvenile justice services depends on the
      development of clear models and sound measurement. Efforts in other child serving
      systems offer guidance to achieve this goal. A multidimensional working model
      developed with parents involved in child protective services is presented as a
      template for developing a model for parental involvement in juvenile justice.
      Features of the model requiring changes to make it more adaptable to juvenile
      justice are identified. A systematic research agenda for developing methods and
      measures to meet the present demands for enhanced parental involvement in
      juvenile justice services is presented.

PMID- 24748705
TI  - Structural and mechanical evolution of reactively and non-reactively sputtered Zr
      Al-N thin films during annealing.
AB  - The influence of reactive and non-reactive sputtering on structure, mechanical
      properties, and thermal stability of Zr1 - xAlxN thin films during annealing to
      1500  degrees C is investigated in detail. Reactive sputtering of a Zr0.6Al0.4
      target leads to the formation of Zr0.66Al0.34N thin films, mainly composed of
      supersaturated cubic (c) Zr1 - xAlxN with small fractions of (semi-)coherent
      wurtzite (w) AlN domains. Upon annealing, the formation of cubic Zr-rich domains
      and growth of the (semi-)coherent w-AlN domains indicate spinodal-like
      decomposition. Loss of coherency can only be observed for annealing temperatures
      above 1150  degrees C. Following these decomposition processes, the hardness
      remains at the as-deposited value of ~ 29 GPa with annealing up to 1100  degrees
      C. Using a ceramic (ZrN)0.6(AlN)0.4 target and sputtering in Ar atmosphere allows
      preparing c-Zr0.68Al0.32N coatings with a well-defined crystalline single-phase
      cubic structure combined with higher hardnesses of ~ 31 GPa. Due to the absence
      of (semi-)coherent w-AlN domains in the as-deposited state, which could act as
      nucleation sites, the decomposition process of c-Zr1 - xAlxN is retarded. Only
      after annealing at 1270  degrees C, the formation of incoherent w-AlN can be
      detected. Hence, their hardness remains very high with ~ 33 GPa even after
      annealing at 1200  degrees C. The study highlights the importance of controlling
      the deposition process to prepare well-defined coatings with high mechanical
      properties and thermal stability.

PMID- 24748706
TI  - CANCER IN OTHER WORDS? THE ROLE OF METAPHOR IN EMOTION DISCLOSURE IN CANCER
      PATIENTS.
AB  - Despite evidence that nurses may play a crucial part in the wellbeing and
      recovery of cancer patients by facilitating their expression of feelings,
      research is lacking into the emotional content of nurse-patient talk and
      patients' use of language in emotion disclosure. In this study, 23 participating
      nurses in a variety of cancer care settings were asked to tape-record their
      conversations with patients during daily care. A data set of 60 nurse-patient
      conversations was collected. Individual expression of emotion by patients was
      identified through interpretive literary analysis within a framework of
      psychodynamic theory. Overall the picture of emotion disclosure was intense. In
      particular, patients' use of metaphor and figurative language to express their
      distress was powerful and pervasive. Participating nurses demonstrated responsive
      skills but their responses to figurative expression were often problematic. The
      study provides evidence of unconscious processes in nurses' work and advocates
      career-long psychoanalytically informed supervision for nurses to better support
      them in challenging dialogue with cancer patients. Research is needed to evaluate
      the impact of supervision on communications with cancer patients to ensure
      patients have access to appropriate emotional supportive and care.

PMID- 24748708
TI  - XANES studies on Eu-doped fluorozirconate based glass ceramics.
AB  - The influence of adding InF3 as a reducing agent on the oxidation state of Eu in
      fluorochloro- (FCZ) and fluorobromozirconate (FBZ) glass ceramics was
      investigated using x-ray absorption near edge (XANES) and photoluminescence (PL)
      spectroscopy. For both materials, it was found that InF3 decreases the Eu2+-to
      Eu3+ ratio significantly. PL spectroscopy proved that an annealing step leads to
      the formation of Eu-doped BaCl2 and BaBr2 nanocrystals in the FCZ and FBZ
      glasses, respectively. In the case of FCZ glass ceramics the hexagonal phase of
      BaCl2 could be detected in indium-free and InF3-doped ceramics, but only for InF3
      containing FCZ glass ceramics a phase transition of the nanoparticles from
      hexagonal to orthorhombic structure is observed. For the FBZ glass ceramics, the
      hexagonal phase of BaBr2 can be formed with and without indium doping, but only
      in the indium-free case a phase transition to orthorhombic BaBr2 could be found.

PMID- 24748707
TI  - Long-term memory: A review and meta-analysis of studies of declarative and
      procedural memory in specific language impairment.
AB  - This review examined the status of long-term memory systems in specific language
      impairment (SLI), in particular declarative memory and aspects of procedural
      memory. Studies included in the review were identified following a systematic
      search of the literature and findings combined using meta-analysis. This review
      showed individuals with SLI are poorer than age matched controls in the learning
      and retrieval of verbal information from the declarative memory. However, there
      is evidence to suggest that the problems with declarative learning and memory for
      verbal information in SLI might be due to difficulties with verbal working memory
      and language. The learning and retrieval of non-verbal information from
      declarative memory appears relatively intact. In relation to procedural learning
      and memory, evidence indicates poor implicit learning of verbal information.
      Findings pertaining to nonverbal information have been mixed. This review of the
      literature indicates there are now substantial grounds for suspecting that
      multiple memory systems may be implicated in the impairment.

PMID- 24748709
TI  - MULTIGENERATIONAL ASPECTS OF SOCIAL STRATIFICATION: ISSUES FOR FURTHER RESEARCH.
AB  - The articles in this special issue show the vitality and progress of research on
      multigenerational aspects of social mobility, stratification, and inequality. The
      effects of the characteristics and behavior of grandparents and other kin on the
      statuses, resources, and positions of their descendants are best viewed in a
      demographic context. Intergenerational effects work through both the
      intergenerational associations of socioeconomic characteristics and also
      differential fertility and mortality. A combined socioeconomic and demographic
      framework informs a research agenda which addresses the following issues: how
      generational effects combine with variation in age, period, and cohort within
      each generation; distinguishing causal relationships across generations from
      statistical associations; how multigenerational effects vary across socioeconomic
      hierarchies, including the possibility of stronger effects at the extreme top and
      bottom; distinguishing between endowments and investments in intergenerational
      effects; multigenerational effects on associated demographic behaviors and
      outcomes (especially fertility and mortality); optimal tradeoffs among diverse
      types of data on multigenerational processes; and the variability across time and
      place in how kin, education, and other institutions affect stratification.

PMID- 24748711
TI  - On the performance of a retransmission-based synchronizer.
AB  - Designing algorithms for distributed systems that provide a round abstraction is
      often simpler than designing for those that do not provide such an abstraction.
      Further, distributed systems need to tolerate various kinds of failures. The
      concept of a synchronizer deals with both: It constructs rounds and allows
      masking of transmission failures. One simple way of dealing with transmission
      failures is to retransmit a message until it is known that the message was
      successfully received. We calculate the exact value of the average rate of a
      retransmission-based synchronizer in environments with probabilistic message
      loss, within which the synchronizer shows nontrivial timing behavior. We show how
      to make this calculation efficient, and present analytical results on the
      convergence speed. The theoretic results, based on Markov theory, are backed up
      with Monte Carlo simulations.

PMID- 24748712
TI  - How cultural capital, habitus and class influence the responses of older adults
      to the field of contemporary visual art.
AB  - This article explores the responses of 38 older people to contemporary visual art
      through the results of a 28-month study entitled, Contemporary Visual Art and
      Identity Construction: Wellbeing amongst Older People. A framework for the
      analysis is provided by previous work on the consumption of art and by Bourdieu's
      constructs of cultural capital, habitus and field. Five groups of older people,
      with a range of different backgrounds, were taken to galleries and their
      responses were recorded, transcribed and analysed. It is concluded that
      participants' responses are influenced by their cultural capital, habitus and
      class-which, in turn, are affected by their life course experiences. Those who
      could not recognise the field (e.g., did not view contemporary art as "art")
      created their own meanings that they associated with the artworks. Evidence
      indicates that group dynamics and class mobility are likewise important.
      Participants also used the experience to respond to real or anticipated age
      associated deficits.

PMID- 24748710
TI  - Bioinspired Hydrogenase Models: The Mixed-Valence Triiron Complex [Fe3(CO)7(MU
      edt)2] and Phosphine Derivatives [Fe3(CO)7-x (PPh3) x (MU-edt)2] (x = 1, 2) and
      [Fe3(CO)5(kappa2-diphosphine)(MU-edt)2] as Proton Reduction Catalysts.
AB  - The mixed-valence triiron complexes [Fe3(CO)7-x (PPh3) x (MU-edt)2] (x = 0-2; edt
      = SCH2CH2S) and [Fe3(CO)5(kappa2-diphosphine)(MU-edt)2] (diphosphine = dppv,
      dppe, dppb, dppn) have been prepared and structurally characterized. All adopt an
      anti arrangement of the dithiolate bridges, and PPh3 substitution occurs at the
      apical positions of the outer iron atoms, while the diphosphine complexes exist
      only in the dibasal form in both the solid state and solution. The carbonyl on
      the central iron atom is semibridging, and this leads to a rotated structure
      between the bridged diiron center. IR studies reveal that all complexes are inert
      to protonation by HBF4.Et2O, but addition of acid to the pentacarbonyl complexes
      results in one-electron oxidation to yield the moderately stable cations
      [Fe3(CO)5(PPh3)2(MU-edt)2]+ and [Fe3(CO)5(kappa2-diphosphine)(MU-edt)2]+, species
      which also result upon oxidation by [Cp2Fe][PF6]. The electrochemistry of the
      formally Fe(I)-Fe(II)-Fe(I) complexes has been investigated. Each undergoes a
      quasi-reversible oxidation, the potential of which is sensitive to phosphine
      substitution, generally occurring between 0.15 and 0.50 V, although
      [Fe3(CO)5(PPh3)2(MU-edt)2] is oxidized at -0.05 V. Reduction of all complexes is
      irreversible and is again sensitive to phosphine substitution, varying between 
      1.47 V for [Fe3(CO)7(MU-edt)2] and around -1.7 V for phosphine-substituted
      complexes. In their one-electron-reduced states, all complexes are catalysts for
      the reduction of protons to hydrogen, the catalytic overpotential being increased
      upon successive phosphine substitution. In comparison to the diiron complex
      [Fe2(CO)6(MU-edt)], [Fe3(CO)7(MU-edt)2] catalyzes proton reduction at 0.36 V less
      negative potentials. Electronic structure calculations have been carried out in
      order to fully elucidate the nature of the oxidation and reduction processes. In
      all complexes, the HOMO comprises an iron-iron bonding orbital localized between
      the two iron atoms not ligated by the semibridging carbonyl, while the LUMO is
      highly delocalized in nature and is antibonding between both pairs of iron atoms
      but also contains an antibonding dithiolate interaction.

PMID- 24748713
TI  - Involving Communities in the Targeting of Cash Transfer Programs for Vulnerable
      Children: Opportunities and Challenges.
AB  - We used baseline data, collected in July-September 2009, from a randomized
      controlled trial of a cash transfer program for vulnerable children in eastern
      Zimbabwe to investigate the effectiveness, coverage, and efficiency of census-
      and community-based targeting methods for reaching vulnerable children. Focus
      group discussions and in-depth interviews with beneficiaries and other
      stakeholders were used to explore community perspectives on targeting. Community
      members reported that their participation improved ownership and reduced conflict
      and jealousy. However, all the methods failed to target a large proportion of
      vulnerable children and there was poor agreement between the community- and
      census-based methods.

PMID- 24748714
TI  - Multi-element geochemical mapping in Southern China.
AB  - The 76-element Geochemical Mapping (76 GEM) Project was undertaken in
      southwestern China in 2000 and in southeastern China in 2008. In this project,
      5244 composite samples of stream sediment at a density of one composite sample
      for each 1:50,000-scale map sheet were prepared from sample archives of the China
      Regional Geochemistry-National Reconnaissance (RGNR) Project, which have been
      available since 1978. The 76 elements were analyzed by using inductively coupled
      plasma mass spectrometry (ICP-MS), X-ray fluorescence (XRF), and inductively
      coupled plasma atomic emission spectroscopy (ICP-AES). In the present study, a
      new quality-control method known as the visualized standard map method was
      applied to the results of the 76 GEM project. Mean value and background value,
      which indicate the average concentration of the 76 elements in southern China,
      were derived from statistical data. Moreover, geochemical maps were compiled to
      demonstrate the distribution of the 76 elements in southern China.

PMID- 24748715
TI  - Expression analysis of abscisic acid (ABA) and metabolic signalling factors in
      developing endosperm and embryo of barley.
AB  - The expression of genes encoding components of ABA and metabolic signalling
      pathways in developing barley endosperm and embryo was investigated. The genes
      included HvRCAR35_47387 and HvRCAR35_2538 (encoding ABA receptors), HvABI1d
      (protein phosphatase 2C), HvSnRK2.4, HvSnRK2.6 and HvPKABA1 (SnRK2-type protein
      kinases) and HvABI5 (ABA response element binding protein; AREBP), as well as two
      genes encoding SnRK1-type protein kinases. Both SnRK1 and SnRK2 phosphorylate
      AREBPs, but SnRK2 is activated by ABA whereas SnRK1 may be broken down. Multiple
      cereal AREBPs with two conserved SnRK1/2 target sites and another class of BZIP
      transcription factors with SnRK1/2 binding sites, including HvBLZ1, were
      identified. Barley grain (cv. Triumph) was sampled at 15, 20, 25 and 30 days post
      anthesis (dpa). HvRCAR35_47387, HvABI1d, HvSnRK2.4 and HvABI5 were expressed
      highly in the endosperm but at much lower levels in the embryo. Conversely,
      HvPKABA1 and HvRCAR35_2538 were expressed at higher levels in the embryo than the
      endosperm, while HvSnRK2.6 was expressed at similar levels in both.
      HvRCAR35_47387, HvABI1d, HvSnRK2.4 and HvABI5 all peaked in expression in the
      endosperm at 20 dpa. A model is proposed in which ABA brings about a transition
      from a SnRK1-dominated state in the endosperm during grain filling to a SnRK2
      dominated state during maturation.

PMID- 24748716
TI  - Use of advanced recombinant lines to study the impact and potential of mutations
      affecting starch synthesis in barley.
AB  - The effects on barley starch and grain properties of four starch synthesis
      mutations were studied during the introgression of the mutations from diverse
      backgrounds into an elite variety. The lys5f (ADPglucose transporter), wax
      (granule-bound starch synthase), isa1 (debranching enzyme isoamylase 1) and sex6
      (starch synthase IIa) mutations were introgressed into NFC Tipple to give mutant
      and wild-type BC2F4 families with different genomic contributions of the donor
      parent. Comparison of starch and grain properties between the donor parents, the
      BC2F4 families and NFC Tipple allowed the effects of the mutations to be
      distinguished from genetic background effects. The wax and sex6 mutations had
      marked effects on starch properties regardless of genetic background. The sex6
      mutation conditioned low grain weight and starch content, but the wax mutation
      did not. The lys5 mutation conditioned low grain weight and starch content, but
      exceptionally high beta-glucan contents. The isa1 mutation promotes synthesis of
      soluble alpha-glucan (phytoglycogen). Its introgression into NFC Tipple increased
      grain weight and total alpha-glucan content relative to the donor parent, but
      reduced the ratio of phytoglycogen to starch. This study shows that introgression
      of mutations into a common, commercial background provides new insights that
      could not be gained from the donor parent.

PMID- 24748718
TI  - Quantifying Engagement: Measuring Player Involvement in Human-Avatar
      Interactions.
AB  - This research investigated the merits of using an established system for rating
      behavioral cues of involvement in human dyadic interactions (i.e., face-to-face
      conversation) to measure involvement in human-avatar interactions. Gameplay audio
      video and self-report data from a Feasibility Trial and Free Choice study of an
      effective peer resistance skill building simulation game (DRAMA-RAMATM) were used
      to evaluate reliability and validity of the rating system when applied to human
      avatar interactions. The Free Choice study used a revised game prototype that was
      altered to be more engaging. Both studies involved girls enrolled in a public
      middle school in Central Florida that served a predominately Hispanic (greater
      than 80%), low-income student population. Audio-video data were coded by two
      raters, trained in the rating system. Self-report data were generated using
      measures of perceived realism, predictability and flow administered immediately
      after game play. Hypotheses for reliability and validity were supported:
      Reliability values mirrored those found in the human dyadic interaction
      literature. Validity was supported by factor analysis, significantly higher
      levels of involvement in Free Choice as compared to Feasibility Trial players,
      and correlations between involvement dimension sub scores and self-report
      measures. Results have implications for the science of both skill-training
      intervention research and game design.

PMID- 24748717
TI  - Neural Encoding of Speech and Music: Implications for Hearing Speech in Noise.
AB  - Understanding speech in a background of competing noise is challenging,
      especially for individuals with hearing loss or deficits in auditory processing
      ability. The ability to hear in background noise cannot be predicted from the
      audiogram, an assessment of peripheral hearing ability; therefore, it is
      important to consider the impact of central and cognitive factors on speech-in
      noise perception. Auditory processing in complex environments is reflected in
      neural encoding of pitch, timing, and timbre, the crucial elements of speech and
      music. Musical expertise in processing pitch, timing, and timbre may transfer to
      enhancements in speech-in-noise perception due to shared neural pathways for
      speech and music. Through cognitive-sensory interactions, musicians develop
      skills enabling them to selectively listen to relevant signals embedded in a
      network of melodies and harmonies, and this experience leads in turn to enhanced
      ability to focus on one voice in a background of other voices. Here we review
      recent work examining the biological mechanisms of speech and music perception
      and the potential for musical experience to ameliorate speech-in-noise listening
      difficulties.

PMID- 24748719
TI  - A new large - Scale synthesis of magnesium oxide nanowires: Structural and
      antibacterial properties.
AB  - Large-scale one-dimensional magnesium oxide (MgO) nanowires with diameters of 6
      nm and lengths of 10 MUm have been successfully synthesized by a new facile and
      simple reaction. This production was performed via a microwave hydrothermal
      approach at low temperature growth of 180  degrees C for 30 min. The structure of
      as synthesized MgO nanowires were investigated by means of X-ray diffraction (X
      ray), Fourier Transformation Infrared Spectroscopy (FTIR), Field Emission
      Scanning Electron Microscopy (FE-SEM), Transmission Electron Microscopy (TEM),
      Selected Area Electron Diffraction (SAED) and Energy Dispersive X-ray (EDS). The
      antibacterial behavior of MgO nanowires concentration in solid media against Gram
      negative and Gram positive for different bacteria has been tested in details. The
      results show that the MgO nanowires have bacteriostatic activity against
      Escherichia coli and Bacillus sp. The antibacterial activity increases with
      increasing MgO nanowires concentration. Furthermore, the presence of one
      dimensional MgO nanowires has high antibacterial efficacy and damages the
      membrane wall of bacteria. Finally, this study offered the prospect of developing
      ultrafine nanoscale devices utilizing MgO nanowires and implementing their useful
      potential in biological control.

PMID- 24748720
TI  - What do Different Beliefs Tell us? An Examination of Factual, Opinion-Based, and
      Religious Beliefs.
AB  - Children and adults differentiate statements of religious belief from statements
      of fact and opinion, but the basis of that differentiation remains unclear.
      Across three experiments, adults and 8-10-year-old children heard statements of
      factual, opinion-based, and religious belief. Adults and children judged that
      statements of factual belief revealed more about the world, statements of opinion
      revealed more about individuals, and statements of religious belief provided
      information about both. Children-unlike adults-judged that statements of
      religious belief revealed more about the world than the believer. These results
      led to three conclusions. First, judgments concerning the relative amount of
      information statements of religious belief provide about individuals change
      across development, perhaps because adults have more experience with diversity.
      Second, recognizing that statements of religious belief provide information about
      both the world and the believer does not require protracted learning. Third,
      statements of religious belief are interpreted as amalgams of factual and opinion
      based statements.

PMID- 24748721
TI  - Highly Luminescent, Size- and Shape-Tunable Copper Indium Selenide Based
      Colloidal Nanocrystals.
AB  - We report a simple, high-yield colloidal synthesis of copper indium selenide
      nanocrystals (CISe NCs) based on a silylamide-promoted approach. The silylamide
      anions increase the nucleation rate, which results in small-sized NCs exhibiting
      high luminescence and constant NC stoichiometry and crystal structure regardless
      of the NC size and shape. In particular, by systematically varying synthesis time
      and temperature, we show that the size of the CISe NCs can be precisely
      controlled to be between 2.7 and 7.9 nm with size distributions down to 9-10%. By
      introducing a specific concentration of silylamide-anions in the reaction
      mixture, the shape of CISe NCs can be preselected to be either spherical or
      tetrahedral. Optical properties of these CISe NCs span from the visible to near
      infrared region with peak luminescence wavelengths of 700 to 1200 nm. The
      luminescence efficiency improves from 10 to 15% to record values of 50-60% by
      overcoating as-prepared CISe NCs with ZnSe or ZnS shells, highlighting their
      potential for applications such as biolabeling and solid state lighting.

PMID- 24748723
TI  - Automated parameterisation for multi-scale image segmentation on multiple layers.
AB  - We introduce a new automated approach to parameterising multi-scale image
      segmentation of multiple layers, and we implemented it as a generic tool for the
      eCognition(r) software. This approach relies on the potential of the local
      variance (LV) to detect scale transitions in geospatial data. The tool detects
      the number of layers added to a project and segments them iteratively with a
      multiresolution segmentation algorithm in a bottom-up approach, where the scale
      factor in the segmentation, namely, the scale parameter (SP), increases with a
      constant increment. The average LV value of the objects in all of the layers is
      computed and serves as a condition for stopping the iterations: when a scale
      level records an LV value that is equal to or lower than the previous value, the
      iteration ends, and the objects segmented in the previous level are retained.
      Three orders of magnitude of SP lags produce a corresponding number of scale
      levels. Tests on very high resolution imagery provided satisfactory results for
      generic applicability. The tool has a significant potential for enabling
      objectivity and automation of GEOBIA analysis.

PMID- 24748722
TI  - Iron-Loaded Magnetic Nanocapsules for pH-Triggered Drug Release and MRI Imaging.
AB  - Magnetic nanocapsules were synthesized for controlled drug release, magnetically
      assisted delivery, and MRI imaging. These magnetic nanocapsules, consisting of a
      stable iron nanocore and a mesoporous silica shell, were synthesized by
      controlled encapsulation of ellipsoidal hematite in silica, partial etching of
      the hematite core in acid, and reduction of the core by hydrogen. The iron core
      provided a high saturation magnetization and was stable against oxidation for at
      least 6 months in air and 1 month in aqueous solution. The hollow space between
      the iron core and mesoporous silica shell was used to load anticancer drug and a
      T1-weighted MRI contrast agent (Gd-DTPA). These multifunctional monodispersed
      magnetic "nanoeyes" were coated by multiple polyelectrolyte layers of
      biocompatible poly-l-lysine and sodium alginate to control the drug release as a
      function of pH. We studied pH-controlled release, magnetic hysteresis curves, and
      T1/T2 MRI contrast of the magnetic nanoeyes. They also served as MRI contrast
      agents with relaxivities of 8.6 mM-1 s-1 (r1) and 285 mM-1 s-1 (r2).

PMID- 24748724
TI  - Time-resolved digital holographic microscopy of laser-induced forward transfer
      process.
AB  - We develop a method for time-resolved digital holographic microscopy to obtain
      time-resolved 3-D deformation measurements of laser induced forward transfer
      (LIFT) processes. We demonstrate nanometer axial resolution and nanosecond
      temporal resolution of our method which is suitable for measuring dynamic
      morphological changes in LIFT target materials. Such measurements provide insight
      into the early dynamics of the LIFT process and a means to examine the effect of
      laser and material parameters on LIFT process dynamics.

PMID- 24748725
TI  - ZZ-Type a posteriori error estimators for adaptive boundary element methods on a
      curve.
AB  - In the context of the adaptive finite element method (FEM), ZZ-error estimators
      named after Zienkiewicz and Zhu (1987) [52] are mathematically well-established
      and widely used in practice. In this work, we propose and analyze ZZ-type error
      estimators for the adaptive boundary element method (BEM). We consider weakly
      singular and hyper-singular integral equations and prove, in particular,
      convergence of the related adaptive mesh-refining algorithms. Throughout, the
      theoretical findings are underlined by numerical experiments.

PMID- 24748726
TI  - Biofuels and the role of space in sustainable innovation journeys.
AB  - This paper aims to identify the lessons that should be learnt from how biofuels
      have been envisioned from the aftermath of the oil shocks of the 1970s to the
      present, and how these visions compare with biofuel production networks emerging
      in the 2000s. Working at the interface of sustainable innovation journey research
      and geographical theories on the spatial unevenness of sustainability transition
      projects, we show how the biofuels controversy is linked to characteristics of
      globalised industrial agricultural systems. The legitimacy problems of biofuels
      cannot be addressed by sustainability indicators or new technologies alone since
      they arise from the spatial ordering of biofuel production. In the 1970-80s,
      promoters of bioenergy anticipated current concerns about food security
      implications but envisioned bioenergy production to be territorially embedded at
      national or local scales where these issues would be managed. Where the
      territorial and scalar vision was breached, it was to imagine poorer countries
      exporting higher-value biofuel to the North rather than the raw material as in
      the controversial global biomass commodity chains of today. However, controversy
      now extends to the global impacts of national biofuel systems on food security
      and greenhouse gas emissions, and to their local impacts becoming more widely
      known. South/South and North/North trade conflicts are also emerging as are
      questions over biodegradable wastes and agricultural residues as global
      commodities. As assumptions of a food-versus-fuel conflict have come to be
      challenged, legitimacy questions over global agri-business and trade are
      spotlighted even further. In this context, visions of biofuel development that
      address these broader issues might be promising. These include large-scale
      biomass-for-fuel models in Europe that would transform global trade rules to
      allow small farmers in the global South to compete, and small-scale biofuel
      systems developed to address local energy needs in the South.

PMID- 24748727
TI  - Parsing Anhedonia: Translational Models of Reward-Processing Deficits in
      Psychopathology.
AB  - The term anhedonia has long been used in the psychiatric literature to describe
      reward-processing dysfunction in psychopathology, especially depression and
      schizophrenia. Although anhedonia literally describes a lack of pleasurable
      experiences in everyday life, recent advances in both the basic science and
      clinical literatures indicate that reward deficits in these disorders are much
      broader than hedonic responses. In this article, we summarize some of the recent
      theoretical and empirical advances in understanding deficits in reward processing
      and their neurobehavioral mechanisms, with a particular focus on the neural
      underpinnings of motivation and effort-based decision making. We also highlight
      the potential of translational neuroscience to enhance diagnostic clarity by
      defining clinical symptoms in terms of underlying pathophysiology.

PMID- 24748728
TI  - Furosemide and Potassium Chloride-induced Alteration in Protein Profile of Left
      Ventricle and its Associated Risk for Sudden Cardiac Death.
AB  - BACKGROUND: Potassium ion (K(+)) plays an essential role in maintaining the
      electrical potential across the plasma membrane of cells. An abnormal serum K(+)
      level is associated with increased risk of ventricular arrhythmia and sudden
      cardiac death (SCD) and these patients are generally prescribed with furosemide
      and potassium chloride (KCl). We explored the association between the use of
      these drugs and the risk of SCD by analyzing biochemical parameters and proteomic
      changes. MATERIALS AND METHODS: The rats were administered with furosemide and
      KCl and their effect was analyzed by studying cardiac and oxidative markers,
      electrolyte content and histopathology. Two-dimensional gel electrophoresis (2
      DE) and electrospray ionization-mass spectrometry were performed to investigate
      the LV proteomic changes. RESULTS: Furosemide and KCl treatments showed
      significant effect on physiological and biochemical parameters, and LV
      histopathology of experimental rats. Proteomic analysis indicated 17
      differentially expressed proteins. Among them, eight protein spots were
      identified using peptide mass fingerprinting. In furosemide-treated group, four
      proteins were upregulated and two proteins were downregulated when compared to 2
      DE proteomic profile of control. While in KCl-treated rats, seven proteins were
      found downregulated. CONCLUSION: [corrected] The present study revealed the
      differential expression of proteins by furosemide and KCl treatment. Thus, the
      results suggest that the use of these drugs leads to proteomic alteration, which
      involve in cardiac conductivity that might increase the risk of SCD.

PMID- 24748729
TI  - Efficacy of crude extract of Emblica officinalis (amla) in arsenic-induced
      oxidative damage and apoptosis in splenocytes of mice.
AB  - INTRODUCTION: Arsenic, an environmental contaminant naturally occurred in
      groundwater and has been found to be associated with immune-related health
      problems in humans. OBJECTIVE: In view of increasing risk of arsenic exposure due
      to occupational and non-occupational settings, the present study has been focused
      to investigate the protective efficacy of amla against arsenic-induced
      spleenomegaly in mice. RESULTS: Arsenic exposures (3 mg/kg body weight p.o for 30
      days) in mice caused an increase production of ROS (76%), lipid peroxidation
      (84%) and decrease in the levels of superoxide dismutase (53%) and catalase (54%)
      in spleen as compared to controls. Arsenic exposure to mice also caused a
      significant increase in caspases-3 activity (2.8 fold) and decreases cell
      viability (44%), mitochondrial membrane potential (47%) linked with apoptosis
      assessed by the cell cycle analysis (subG1-28.72%) and annexin V/PI binding in
      spleen as compared to controls. Simultaneous treatment of arsenic and amla (500
      mg/kg body weight p.o for 30 days) in mice decreased the levels of lipid
      peroxidation (33%), ROS production (24%), activity of caspase-3 (1.4 fold),
      apoptosis (subG1 12.72%) and increased cell viability (63%), levels superoxide
      dismutase (80%), catalase (77%) and mitochondrial membrane potential (66%) as
      compared to mice treated with arsenic alone. CONCLUSIONS: Results of the present
      study indicate that the effect of arsenic is mainly due to the depletion of
      glutathione in liver associated with enhanced oxidative stress that has been
      found to be protected following simultaneous treatment of arsenic and amla.

PMID- 24748730
TI  - Tobacco dust induced genotoxicity as an occupational hazard in workers of bidi
      making cottage industry of central India.
AB  - CONTEXT: To explore genotoxicity in bidi rollers occupationally exposed to bidi
      tobacco dust. AIMS: To assess the extent of genotoxicity of tobacco dust to bidi
      rollers of Jabalpur, Madhya Pradesh, India and cytotoxicity of bidi tobacco
      extract. SETTINGS AND DESIGN: Blood samples from 31 bidi rollers and 30 controls
      taken after written informed consent were analyzed for chromosome aberrations
      (CA) and comet assay. MATERIALS AND METHODS: Genotoxicity was studied by CA in
      cultured peripheral blood lymphocytes of bidi rollers and the deoxyribonucleic
      acid (DNA) damage studies were done by comet assay of their blood. The toxicity
      of bidi tobacco extract to normal human lymphocytes was studied by MMT (3-[4,5
      dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) assay as drop in
      viability. STATISTICAL ANALYSIS USED: Student's t-test and DMRT. RESULTS: There
      is a general trend of increase in CA% of both in exposed and control groups with
      age, but in every group the bidi rollers have a significantly higher CA% than the
      controls. The CA % is also directly related to exposure. The comet assay findings
      reveal that the mean comet length and tail length increases with exposure time.
      The toxicity of bidi tobacco extract (TE) to normal human lymphocytes was tested
      in vitro by 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT)
      assay at 2 h of incubation. The trend of drop in viability with increasing
      concentrations of TE was clearly evident from the data from four donors in spite
      of their individual differences in viability. CONCLUSIONS: The results obtained
      in this investigation indicate that bidi rollers seem to be facing the
      occupational hazard of genotoxicity due to handling bidi tobacco and inhalation
      of tobacco dust. They should be advised to work under well-ventilated conditions.

PMID- 24748731
TI  - Assessment of genotoxic potential of arsenic in female albino rats at permissible
      dose levels.
AB  - BACKGROUND: Arsenic is a wide spread environmental contaminant and has been
      recognized as a genotoxic element which is of major public health concern. AIM:
      The present study evaluates the genotoxic potential of arsenic at low permissible
      dose levels. MATERIALS AND METHODS: Forty-eight mature female rats were divided
      into four groups of 12 animals each. Group I animals received distilled water and
      served as control. Group II-IV animals received sodium arsenite dissolved in
      distilled water continuously for a period of 60 days at the dose of 10, 30 and 50
      MUg/L (ppb) respectively. Six rats from each group were sacrificed after 30 days
      of arsenic exposure and the remaining animals were sacrificed after 60 days.
      Liver was excised from the sacrificed animals to study the probable advent signs
      of carcinogenicity measured through microsomal degranulation test. Assessment of
      mutagenic potential of arsenic was evaluated through chromosomal aberrations
      observed in the bone marrow cells. RESULTS: The levels of RNA and proteins
      decreased significantly (P <= 0.01) in all the three doses administered along
      with an increase in % microsomal degranulation in hepatic fraction when compared
      to control at both 30 and 60 days time period. A dose-dependent increase in
      chromosome aberrations like fragmentation, breakage has been observed in all the
      treated animals. CONCLUSION: The results of present study revealed that chronic
      exposure of arsenic even at its low permissible dose limits results in
      carcinogenic and mutagenic effects which emphasize its genotoxic possibility.

PMID- 24748732
TI  - Ameliorative Effects of Operculina turpethum and its Isolated Stigma-5,22dien-3-o
      beta-D-glucopyranoside on the Hematological Parameters of Male Mice Exposed to N
      Nitrosodimethylamine, a Potent Carcinogen.
AB  - OBJECTIVES: Enormous propensity of plants to synthesize a variety of structurally
      diverse bioactive compounds, has made the plant kingdom a potential source of
      chemical constituents with various therapeutic values, including antitumor and
      cytotoxic activities. Blood is a good indicator to determine the physiological
      and pathological status of man and animal. The objective of the present study is
      to determine the effect of Operculina turpethum root extract and its isolated
      glycoside treatment on the hematological parameters in the mice with N
      Nitrosodimethylamine (NDMA) induced cancer. MATERIALS AND METHODS: The body
      weights of the animals were recorded before and after the experiment. Non
      coagulated blood was tested for total erythrocyte count, total leukocyte count,
      hemoglobin, differential leukocyte count (DLC) and for other blood indices.
      RESULTS: A significant (P < 0.01), (P < 0.001) recovery of the red blood cell and
      white blood cell counts, packed cell volume and hemoglobin content in the host
      after 21 day treatment was shown. CONCLUSION: These results show that the extract
      of Operculina turpethum is relatively safe following oral administration and have
      possible stimulatory effect on red blood cell production and there was dose
      dependent therapeutic effect.

PMID- 24748733
TI  - Protective Assessment of Euphorbia neriifolia and its Isolated Flavonoid Against
      N-nitrosodiethylamine-induced Hepatic Carcinogenesis in Male Mice: A
      Histopathological Analysis.
AB  - AIMS: The aim of this study was to examine the impacts of N-nitrosodiethylamine
      (DENA), a potent environment carcinogen on liver tissue of mice which was
      attenuated by isolated flavonoid and hydro-ethanolic extract of Euphorbia
      neriifolia (HEEN) leaves. MATERIALS AND METHODS: Carcinogenicity was induced in
      albino mice by a single oral administration of DENA (50 mg/kg body weight). The
      HEEN (150 and 400 mg/kg body weight), butylated hydroxyanisole (BHA; 0.5 and 1%)
      and E. neriifolia flavonoid (ENF; 50 mg/kg body weight) were estimated to examine
      the possible anti-cancer potential. RESULTS: DENA exposed animals showed
      alterations in normal hepatic histo-architecture, which comprised of necrosis
      (N), dilated sinusoids and vacuolization of the cells. Mice treated with E.
      neriifolia lower (ENL) and higher (ENH) dose and ENF before intoxicated with DENA
      showed that the liver cells were normal, with very little necrosis (Day 31). On
      the other hand, BHA higher (BHAH) and lower (BHAL) dose failed to diminish the
      abnormalities caused by the DENA. CONCLUSION: Results of the present study
      suggests that the ENH and ENF protects the hepatic tissue against DENA-induced
      hepatic carcinoma. The results could also be expressed in the order of ENH> ENF>
      ENL> BHAH> BHAL.

PMID- 24748734
TI  - 28-homobrassinolide alters protein content and activities of glutathione-s
      transferase and polyphenol oxidase in raphanus sativus L. Plants under heavy
      metal stress.
AB  - OBJECTIVES: The application of brassinosteroids (BRs), the plant steroidal
      hormones, results in an increased tolerance toward stress and thus helps
      improving the yield of crop plants. The present study was carried out to
      investigate the effect of 28-homobrassinolide (28-HBL) on the protein content as
      well as activities of antioxidant enzymes viz., glutathione-s-transferase (GST)
      and polyphenol oxidase (PPO) in radish plants grown under Cadmium (Cd) and
      Mercury (Hg) metal stress. MATERIALS AND METHODS: Shoots of 60 and 90 days old
      radish plants, grown under Cd and Hg metal stress (0, 0.5, 1.0, 1.5 mM) and given
      the presowing treatment of 28-HBL (0, 10(-7), 10(-9), 10(-11) M) to seeds for 8
      h, were analyzed for protein content and GST and PPO enzyme activities. RESULTS:
      Protein content showed decrease in plants given Cd and Hg metal treatment alone,
      while treatment with 28-HBL enhanced the protein content, suggesting its stress
      protective role. An increase in the activity of antioxidative enzymes was also
      observed in plants stressed with heavy metals as well as in those supplemented
      with 28-HBL. CONCLUSIONS: In the present investigation, the activity of
      antioxidative enzymes was found to increase due to metal stress and a further
      increase was noticed in plants given both metal and 28-HBL treatment, suggesting
      the stress protective role of 28-HBL via modulating the antioxidative enzymes.

PMID- 24748735
TI  - Assessment of Toxicity of Monocrotophos in Freshwater Bivalve, Lamellidens
      marginalis, Using Different Markers.
AB  - The present study was undertaken to evaluate the toxic effects of monocrotophos,
      a widely used organophosphorus pesticide, on Lamellidens marginalis with a wide
      battery of biomarkers consisting of AchE inhibition, lipid peroxidation, the
      levels of antioxidant enzymes, and histopathological changes. Animals were
      exposed to monocrotophos (52.36 mg/l) for four days. Malondialdehyde (MDA) values
      were measured as index of oxidation while Superoxide dismutase (SOD), Catalase
      (CAT), Glutathione s-Transferase (GST), and Glutathione-Reductase (GR) were
      measured as index of an antioxidant status. After exposure, a significant
      reduction of the capability to neutralize radicals was observed.
      Histopathological changes, such as fibrosis in gill filaments and hypertrophy in
      mucous cells of foot tissue, were observed after treatment. In a second series of
      experiment, exposed animals were thereafter transferred to clean water and kept
      in it up to 28 days to assess the recovery pattern. Significant recovery is
      observed in AchE and antioxidant enzymes. Oxidative damage observed after acute
      exposure indicate that mussels faced an oxidative challenge but were able to
      counteract, as values of anti-oxidants returned near to control values after 28
      days. Altered activities in anti-oxidant enzymes due to stress recovered well
      after 28 days in gill and muscles as compared to foot and mantle. Overall results
      suggested that oxidative markers are highly sensitive and could be profitably
      applied to freshwater mussels for environmental quality assessment in freshwater.

PMID- 24748736
TI  - Time-Dependent Regulation of Apoptosis by AEN and BAX in Response to 2
      Aminoanthracene Dietary Consumption.
AB  - BACKGROUND/OBJECTIVE: The modulation of the toxic effects of 2-aminoanthracene
      (2AA) on the liver by apoptosis was investigated. Fisher-344 (F344) rats were
      exposed to various concentrations of 2AA for 14 and 28 days. The arylamine 2AA is
      an aromatic hydrocarbon employed in manufacturing chemicals, dyes, inks, and it
      is also a curing agent in epoxy resins and polyurethanes. 2AA has been detected
      in tobacco smoke and cooked foods. METHODS: Analysis of total messenger
      ribonucleic acid (mRNA) extracts from liver for apoptosis-related gene expression
      changes in apoptosis enhancing nuclease (AEN), Bcl2-associated X protein (BAX),
      CASP3, Jun proto-oncogene (JUN), murine double minute-2 p53 binding protein
      homolog (MDM2), tumor protein p53 (p53), and GAPDH genes by quantitative real
      time polymerase chain reaction (qRT-PCR) was coupled with terminal
      deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and caspase-3 (Casp3)
      activity assays. RESULTS: Specific apoptosis staining result does not seem to
      show significant difference between control and treated animals. This may be due
      to freeze-thaw artifacts observed in the liver samples. However, there appears to
      be a greater level of apoptosis in medium- and high-dose (MD and HD) 2AA treated
      animals. Analyses of apoptosis-related genes seem to show AEN and BAX as the main
      targets in the induction of apoptosis in response to 2AA exposure, though p53,
      MDM2, and JUN may play supporting roles. CONCLUSION: Dose-dependent increases in
      mRNA expression were observed in all genes except Casp3. BAX was very highly
      expressed in the HD rats belonging to the 2-week exposure group. This trend was
      not observed in the animals treated for 4 weeks. Instead, AEN was rather very
      highly expressed in the liver of the MD animals that were treated with 2AA for 28
      days.

PMID- 24748737
TI  - Serological changes induced by blend of sunset yellow, metanil yellow and
      tartrazine in swiss albino rat, rattus norvegicus.
AB  - OBJECTIVE: The present study was carried out to evaluate the toxic effect of
      blend of some food colors on Swiss albino rats. MATERIALS AND METHODS: A blend
      (1:1:1) of sunset yellow, metanil yellow and tartrazine showed additive effects
      on serological parameters which indicate that addition of these dye together in
      food stuff may give rise to more toxic effects than are produced by each dye
      individually. Animals were divided into four groups (I, II, III, and IV). First
      group was treated as control and respective group of animals received 25, 50 and
      75 mg/kg body weight blend of food colors by gavaging up to 30 days. RESULTS: The
      serological study showed a decrease in total protein and albumin and an increase
      in alkaline phosphatase, SGPT and total bilirubin. The results revealed that oral
      administration of these blend did not affect the body weight gain. CONCLUSION:
      The prolonged consumption of the blend may cause adverse effect on human health.

PMID- 24748738
TI  - Cyto-genotoxicity Assessment of Potential Anti-tubercular Drug Candidate Molecule
      trans-cyclohexane-1, 4-diamine Derivative-9u in Human Lung Epithelial Cells A549.
AB  - Increasing incidences of multiple drug-resistance (MDR) in Mycobacterium
      tuberculosis are emerging as one among the serious public health threats and
      socio-economic burden to the third world countries including India. Last couples
      of decades are witnesses of the dedicated and sustained efforts made toward the
      development of target specific and cost-effective antimicrobial agents against
      MDR-M. tuberculosis. However, the drugs in use are still incapable of controlling
      the upsurge of MDR. Thus, in order to address the issue, we synthesized a library
      of symmetrical trans-cyclohexane-1, 4-diamine derivatives and evaluated their
      anti-mycobacterium activity in H37RV strain of M. tuberculosis. A range of
      efficacy has been recorded in different derivatives of synthesized compounds and
      compound "9u" having i-propyl group substitution at p-position, was found to have
      more significant detrimental effects against the tested strain of M.
      tuberculosis. The present investigations were aimed to study whether the
      effective anti-mycobacterium concentrations of "9u" are biologically safe to
      human cells or not? The human lung epithelial cell line-A549 were exposed to a
      range of concentrations, i.e., at and above the anti-mycobacterium effective dose
      of "9u" for a period of 0-96 h. The standard endpoints of cytotoxicity viz.,
      tetrazolium bromide salt (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium
      bromide), neutral red uptake, lactate dehydrogenase release, trypan blue dye
      exclusion assays; and genotoxicity viz., micronucleus and chromosomal aberrations
      assays were used to evaluate the bio-safety of test compound. The compound "9u"
      shows no significant cytotoxicity and genotoxicity in A549 cells exposed to 10(
      5) M for 72 h, a concentration substantially higher than the concentration kill
      the H37Rv strain of M. tuberculosis. The compound 9u was found to be safe up to
      10(-4) M if given for 24 h. The data reveal the therapeutic potential of compound
      9u against M. tuberculosis without any having any cytotoxicity and genotoxicity
      responses. 

PMID- 24748739
TI  - Ameliorative Effect of Tephrosia Purpurea in Arsenic-induced Nephrotoxicity in
      Rats.
AB  - OBJECTIVES: The present investigation was conducted to evaluate the
      nephroprotective activity of Tephrosia purpurea (TPE) against arsenic-induced
      toxicity. MATERIALS AND METHODS: Twenty four number of wistar rats were equally
      divided into three groups. Sodium arsenite (10 mg/kg) was orally given to group I
      for 28 days, additionally group II was orally treated with TPE (500 mg/kg), while
      the control group was kept untreated with neither arsenic nor TPE. Serum
      biomarker levels, oxidative stress indices and arsenic concentration in kidney
      were estimated. Histopathology of kidney was also conducted. RESULTS: Group II
      animals show significantly reduced blood urea nitrogen and plasma creatinine, and
      increased serum albumin level compared to group I. The higher lipid peroxidation
      with exhausted superoxide dismutase activity and reduced glutathione level were
      noticed in group I compared to group II. There was no significant difference in
      arsenic accumulation in kidneys between the two arsenic treated groups, but the
      histopathology of kidney of group II rats revealed reduced necrosis and intact
      tubular architecture as compared to group I. CONCLUSIONS: Tephrosia Purpurea
      extract has a significant role in protecting the animals from arsenic-induced
      nephrotoxicity.

PMID- 24748740
TI  - Genotoxicity Evaluation of Acephate and Profenofos by the PCR-RFLP Assay.
AB  - OBJECTIVES: In this study we have evaluated the genotoxic potential of pesticides
      acephate and profenofos by polymerase chain reaction-restriction fragment length
      polymorphism (PCR-RFLP) assay with the mosquito Culex quinquefasciatus taken as
      experimental model. MATERIAL AND METHODS: Second instar larvae were treated with
      LC20 of each pesticide for 24 h and induced mutations in the sequence of
      mitochondrial 16S rRNA gene were studied from restriction patterns generated with
      PacI and PsiI restriction endonucleases. RESULTS: Variations in the number and
      size of digested fragments were recorded from treated individuals compared with
      controls showing that the restriction enzymes created a cut at different
      locations. In addition, sequences of the 16S gene from control and treated
      individuals were also used to confirm the RFLP patterns. From the sequence
      alignment data, it was found that mutations caused the destruction and generation
      of restriction sites in the gene sequence of treated individuals. CONCLUSION:
      This study indicates that both the pesticides had significant potential to induce
      mutations in the 16S gene of Culex quinquefasciatus.

PMID- 24748741
TI  - Effect of extraction media and storage time on the elution of monomers from four
      contemporary resin composite materials.
AB  - INTRODUCTION: The purpose of this study was to examine the effect of different
      extraction media, including culture media, as well as storage times on the
      elution of monomers from modern dental composites. MATERIALS AND METHODS: FOUR
      CONTEMPORARY COMPOSITE MATERIALS WERE TESTED: (a) Clearfil Majesty Esthetic
      (Kuraray), (b) Esthet X (DENTSPLY), (c) Filtek Silorane (3M ESPE), and (d) Admira
      (Voco). Forty-eight specimens were made. The specimens were stored in 1 ml of (a)
      artificial saliva, (b) Dulbecco's Modified Eagle Medium (DMEM), (c) DMEM plus 10%
      fetal bovine serum (FBS), and (d) ethanol 75%. The specimens were analyzed after
      24 hours and after 1 week of storage. HPLC Liquid Chromatography was performed to
      analyze the extracted solutions. The statistical package SPSS 18 was used for the
      statistical analysis of the results. RESULTS: All the materials tested released
      monomers that were consistent with the base composition of their resin matrix.
      Bisphenol-A (BPA) was detected in Clearfil Esthetic and EsthetX when ethanol 75%
      was used for storage. TEGDMA was released at a faster rate compared to the other
      monomers with most of the monomer eluted in the first 24 hours. The effect of
      storage solution and storage time on the elution of the same monomers varied
      between materials. CONCLUSIONS: There was a significant effect of time, storage
      solution, and material on the elution of the detectable unbound monomers. Unbound
      monomers were detected in culture media, which may lead to false-negative results
      in cytotoxicity tests of resin composite materials. BPA was detected in two of
      the tested materials.

PMID- 24748742
TI  - Protective effect of caffeine on ethyl methanesulfonate-induced wing primordial
      cells of Drosophila melanogaster.
AB  - OBJECTIVES: The antimutagenic effect of caffeine is evaluated against ethyl
      methanesulfonate (EMS)-induced mutation rate in Drosophila. MATERIALS AND
      METHODS: The mutation rate is evaluated using wing mosaic assay. In
      transheterozygous larvae, multiple wing hair (mwh 0.3-3) and flare (flr 3-38.8)
      genes were used as markers of the extent of mutagenicity. RESULTS: The results at
      0.5 and 1.0 mM EMS concentration at both 48 +/- 4 and 72 +/- 4 h have shown
      consistent increase in mutation rate, which was being measured as frequency of
      clone formation per 105 cells. Toxicity of caffeine at 5 mM concentration was
      parallel to that of distilled water alone. At 0.5 mM EMS concentration at 42 +/-
      4 and 72 +/- 4 h, Drosophila larvae mutation rate was significantly increased.
      Although caffeine prevented mutation rate in all pre, post, and combined
      treatment, it was more significant in pretreatment experiments where it was found
      to be effective in reducing the genotoxicity of EMS. However, the concentration
      of caffeine as recommended in dietary allowance did not induce the frequency of
      mutant clones in somatic mutation and recombination test (SMART) recorded.
      CONCLUSION: This study shows that caffeine significantly reduced the genotoxicity
      induced by EMS. However, the limitation in completely abolishing genotoxicity
      induced by EMS as observed at the dietary allowance of caffeine makes it
      interesting for further in-depth study. Further studies on the molecular
      mechanism of antigenotoxic effect of caffeine will also be interesting.

PMID- 24748743
TI  - Adverse Effects of UV-B Radiation on Plants Growing at Schirmacher Oasis, East
      Antarctica.
AB  - This study aimed to assess the impacts of ultraviolet-B (UV-B) radiation over a
      28-day period on the levels of pigments of Umbilicaria aprina and Bryum argenteum
      growing in field. The depletion of stratospheric ozone is most prominent over
      Antarctica, which receives more UV-B radiation than most other parts of the
      planet. Although UV-B radiation adversely affects all flora, Antarctic plants are
      better equipped to survive the damaging effects of UV-B owing to defenses
      provided by UV-B absorbing compounds and other screening pigments. The UV-B
      radiations and daily average ozone values were measured by sun photometer and the
      photosynthetic pigments were analyzed by the standard spectrophotometric methods
      of exposed and unexposed selected plants. The daily average atmospheric ozone
      values were recorded from 5 January to 2 February 2008. The maximum daily average
      for ozone (310.7 Dobson Units (DU)) was recorded on 10 January 2008. On that day,
      average UV-B spectral irradiances were 0.016, 0.071, and 0.186 W m(-2) at
      wavelengths of 305, 312, and 320 nm, respectively. The minimum daily average
      ozone value (278.6 DU) was recorded on 31 January 2008. On that day, average UV-B
      spectral irradiances were 0.018, 0.085, and 0.210 W m(-2) at wavelengths of 305,
      312, and 320 nm, respectively. Our results concludes that following prolonged UV
      B exposure, total chlorophyll levels decreased gradually in both species, whereas
      levels of UV-B absorbing compounds, phenolics, and carotenoids gradually
      increased. 

PMID- 24748744
TI  - Significance of impaired serum gelatinases activities in metabolic syndrome.
AB  - INTRODUCTION: A consortium of metabolic risk factors accelerate the onset of
      diabetes, heart disease, stroke, and certain cancers. Proteolytic enzymes like
      matrix metalloproteinases (MMP) are regulated by a group of endogenous proteins
      called tissue inhibitors of metalloproteinases (TIMP). These TIMPs binds to
      active and alternate sites of activated MMPs and facilitate regulation. Impaired
      expression of MMPs may have a significant contribution in the pathogenesis of
      many tissues-destructive processes like tumor progression and cardiovascular and
      metabolic disorders. MATERIALS AND METHODS: This case control study lays stress
      on the possible role of impaired levels of circulating MMP-2 and 9 in metabolic
      syndrome (MetS). The age, sex-matched 388 subjects with 190 newly diagnosed
      patients, and 198 healthy controls were recruited. To screen the patients with
      MetS, biochemical analysis of patients for impaired glucose level, hypertension,
      body mass index (BMI), and lipid profile was performed. The circulating level of
      MMP-2 and -9 in serum was analyzed by enzyme-linked immunosorbent assay (ELISA)
      in all patients and control. RESULTS: All metabolic risk factors were
      statistically significant (P < 0.01) in patients against control group. The serum
      MMP-2 and -9 level was significantly higher (P < 0.001) in patients having MetS
      as compared with control group. CONCLUSIONS: Similar trend was observed in gender
      wise analysis of serum MMP level. Higher MMP level alteration observed in male
      patients as compared with female patients.

PMID- 24748745
TI  - Pyopneumothorax following kerosene poisoning.
AB  - Kerosene poisoning is a common poisoning in India especially in childhood, and
      clinical spectrum can range from meager chemical pneumonitis to grave
      complications such as hypoxia, pneumothorax, pneumomediastinum, and emphysema.
      Pyopneumothorax that may require aggressive management in the form of thoracotomy
      has not been reported in literature. We hereby report a 22-year young female who
      had developed series of respiratory complications including pyopneumothorax
      following ingestion of kerosene with suicidal intent and was treated
      successfully. 

PMID- 24748746
TI  - Technical workshop on risk based approaches for food safety management.

PMID- 24748748
TI  - Differences in structural elements of Bcr-Abl oncoprotein isoforms in Chronic
      Myelogenous Leukemia.
AB  - in silico modeling, using Psipred and ExPASy servers was employed to determine
      the structural elements of Bcr-Abl oncoprotein (p210(BCR-ABL)) isoforms, b2a2 and
      b3a2, expressed in Chronic Myelogenous Leukemia (CML). Both these proteins are
      tyrosine kinases having masses of 210-kDa and differing only by 25 amino acids
      coded by the b3 exonand an amino acidsubstitution (Glu903Asp). The secondary
      structure elements of the two proteins show differences in five alpha-helices and
      nine beta-strands which relates to differences in the SH3, SH2, SH1 and DNA
      binding domains. These differences can result in different roles played by the
      two isoforms in mediating signal transduction during the course of CML. 

PMID- 24748749
TI  - Computer Aided Screening of Phytochemicals from Garcinia against the Dengue
      NS2B/NS3 Protease.
AB  - Dengue virus NS2/NS3 protease because of its ability to cleave viral proteins is
      considered as an attractive target to screen antiviral agents. Medicinal plants
      contain a variety of phytochemicals that can be used as drug against different
      diseases and infections. Therefore, this study was designed to uncover possible
      phytochemical of different classes (Aromatic, Carbohydrates, Lignin, Saponins,
      Steroids, Tannins, Terpenoids, Xanthones) that could be used as inhibitors
      against the NS2B/NS3 protease of DENV. With the help of molecular docking,
      Garcinia phytochemicals found to be bound deeply inside the active site of DENV
      NS2B/NS3 protease among all tested phytochemicals and had interactions with
      catalytic triad (His51, Asp75, Ser135). Thus, it can be concluded from the study
      that these Gracinia phytochemicals could serve as important inhibitors to inhibit
      the viral replication inside the host cell. Further in-vitro investigations
      require confirming their efficacy. 

PMID- 24748747
TI  - Molecular control of vascular development by the matricellular proteins CCN1
      (Cyr61) and CCN2 (CTGF).
AB  - The circulatory system is the first hierarchically ordered network to form during
      the development of vertebrates as it is an indispensable means of adequate oxygen
      and nutrient delivery to developing organs. During the initial phase of vascular
      development, endothelial lineage-committed cells differentiate, migrate, and
      coalesce to form the central large axial vessels and their branches. The
      subsequent phase of vessel expansion (i.e., angiogenesis) involves a cascade of
      events including endothelial cell migration, proliferation, formation of an
      immature capillary structure, recruitment of mural cells and deposition of a
      basement membrane to yield a functional vasculature. These series of events are
      tightly regulated by the coordinated expression of several angiogenic,
      morphogenic and guidance factors. The extracellular matrix (ECM) is synthesized
      and secreted by embryonic cells at the earliest stages of development and forms a
      pericellular network of bioactive stimulatory and inhibitory angiogenesis
      regulatory factors. Here we describe the role of a subset of inducible immediate
      early gene-encoded, ECM-associated integrin- and heparin-binding proteins
      referred to as CCN1 (or Cyr61) and CCN2 (or CTGF) and their function in the
      development of the vascular system. Gene-targeting experiments in mice have
      identified CCN1 and CCN2 as critical rate-limiting determinants of endothelial
      cell differentiation and quiescence, mural cell recruitment and basement membrane
      formation during embryonic vascular development. Emphasis will be placed on the
      regulation and function of these molecules and their contextual mode of action
      during vascular development. Further understanding of the mechanisms of CCN1- and
      CCN2-mediated blood vessel expansion and remodeling would enhance the prospects
      that these molecules provide for the development of new treatments for vascular
      diseases.

PMID- 24748750
TI  - Modeling and phylogenetic analysis of cytosolic ascorbate peroxidase (OsAPX1)
      from rice reveal signature motifs that may play a role in stress tolerance.
AB  - Ascorbate peroxidase (APX) is a crucial, haeme-containing enzyme of the ascorbate
      glutathione cycle that detoxifies reactive oxygen species in plants by catalyzing
      the conversion of hydrogen peroxide to water using ascorbate as a specific
      electron donor. Different APX isoforms are present in discrete subcellular
      compartments in rice and their expression is stress regulated. We revealed the
      homology model of OsAPX1 protein using the crystal structure of soybean GmAPX1
      (PDB ID: 2XIF) as template by Modeller 9.12. The resultant OsAPX1 model structure
      was refined by PROCHECK, ProSA, Verify3D and RMSD that indicated the model
      structure is reliable with 83 % amino acid sequence identity with template, RMSD
      (1.4 A), Verify3D (86.06 %), Zscores (-8.44) and Ramachandran plot analysis
      showed that conformations for 94.6% of amino acid residues are within the most
      favoured regions. Investigation revealed two conserved signatures for haeme
      ligand binding and peroxidase activity in the alpha helical region that may play
      a significant role during stress. 

PMID- 24748751
TI  - Molecular Modeling and docking of Wheat Hydroquinone Glucosyl transferase by
      using Hydroquinone, Phenyl phosphorodiamate and n-(n butyl) Phosphorothiocic
      Triamide as Inhibitors.
AB  - In agriculture high urease activity during urea fertilization causes substantial
      environmental and economical problems by releasing abnormally large amount of
      ammonia into the atmosphere which leads to plant damage as well as ammonia
      toxicity. All over the world, urea is the most widely applied nitrogen
      fertilizer. Due to the action of enzyme urease; urea nitrogen is lost as volatile
      ammonia. For efficient use of nitrogen fertilizer, urease inhibitor along with
      the urea fertilizer is one of the best promising strategies. Urease inhibitors
      also provide an insight in understanding the mechanism of enzyme catalyzed
      reaction, the role of various amino acids in catalytic activity present at the
      active site of enzyme and the importance of nickel to this metallo enzyme. By
      keeping it in view, the present study was designed to dock three urease
      inhibitors namely Hydroquinone (HQ), Phenyl Phosphorodiamate (PPD) and N-(n
      butyl) Phosphorothiocic triamide (NBPT) against Hydroquinone glucosyltransferase
      using molecular docking approach. The 3D structure of Hydroquinone
      glucosyltransferase was predicted using homology modeling approach and quality of
      the structure was assured using Ramachandran plot. This study revealed important
      interactions among the urease inhibitors and Hydroquinone glucosyltransferase.
      Thus, it can be inferred that these inhibitors may serve as future anti toxic
      constituent against plant toxins. 

PMID- 24748752
TI  - Three-dimensional (3D) structure prediction of the American and African oil-palms
      beta-ketoacyl-[ACP] synthase-II protein by comparative modelling.
AB  - BACKGROUND: The fatty-acid profile of the vegetable oils determines its
      properties and nutritional value. Palm-oil obtained from the African oil-palm
      [Elaeis guineensis Jacq. (Tenera)] contains 44% palmitic acid (C16:0), but, palm
      oil obtained from the American oilpalm [Elaeis oleifera] contains only 25% C16:0.
      In part, the b-ketoacyl-[ACP] synthase II (KASII) [EC: 2.3.1.179] protein is
      responsible for the high level of C16:0 in palm-oil derived from the African oil
      palm. To understand more about E. guineensis KASII (EgKASII) and E. oleifera
      KASII (EoKASII) proteins, it is essential to know its structures. Hence, this
      study was undertaken. OBJECTIVE: The objective of this study was to predict three
      dimensional (3D) structure of EgKASII and EoKASII proteins using molecular
      modelling tools. MATERIALS AND METHODS: The amino-acid sequences for KASII
      proteins were retrieved from the protein database of National Center for
      Biotechnology Information (NCBI), USA. The 3D structures were predicted for both
      proteins using homology modelling and ab-initio technique approach of protein
      structure prediction. The molecular dynamics (MD) simulation was performed to
      refine the predicted structures. The predicted structure models were evaluated
      and root mean square deviation (RMSD) and root mean square fluctuation (RMSF)
      values were calculated. RESULTS: The homology modelling showed that EgKASII and
      EoKASII proteins are 78% and 74% similar with Streptococcus pneumonia KASII and
      Brucella melitensis KASII, respectively. The EgKASII and EoKASII structures
      predicted by using ab-initio technique approach shows 6% and 9% deviation to its
      structures predicted by homology modelling, respectively. The structure
      refinement and validation confirmed that the predicted structures are accurate.
      CONCLUSION: The 3D structures for EgKASII and EoKASII proteins were predicted.
      However, further research is essential to understand the interaction of EgKASII
      and EoKASII proteins with its substrates.

PMID- 24748753
TI  - CARd-3D: Carbon Distribution in 3D Structure Program for Globular Proteins.
AB  - Spatial arrangement of carbon in protein structure is analyzed here.
      Particularly, the carbon fractions around individual atoms are compared. It is
      hoped that it follows the principle of 31.45% carbon around individual atoms. The
      results reveal that globular protein's atoms follow this principle. A comparative
      study on monomer versus dimer reveal that carbon is better distributed in dimeric
      form than in its monomeric form. Similar study on solid versus liquid structures
      reveals that the liquid (NMR) structure has better carbon distribution over the
      corresponding solid (X-Ray) structure. The carbon fraction distributions in fiber
      and toxin protein are compared. Fiber proteins follow the principle of carbon
      fraction distribution. At the same time it has another broad spectrum of carbon
      distribution than in globular proteins. The toxin protein follows an abnormal
      carbon fraction distribution. The carbon fraction distribution plays an important
      role in deciding the structure and shape of proteins. It is hoped to help in
      understanding the protein folding and function. 

PMID- 24748754
TI  - In-Vitro and in-Silico characterization of Sophora interrupta plant extract as an
      anticancer activity.
AB  - Sophora interrupta belongs to the family of Fabaceae and the species in this
      genus have a diverse medicinal importance as a folk medicine for preventing many
      ailments including cancer. In order to evaluate the anticancer activity of
      S.interrupta, we have performed in vitro anti-oxidant, anti-inflammatory, anti
      proliferative, and cell based anticancer activity in MCF-7 and PC-3 cell lines.
      Secondary metabolites of S.interrupta were used to identify anticancer compounds
      using Open Eye software. The antioxidant activity of the S.interrupta root
      ethylacetate (SEA) extract at 100 ug/ml is equal to that of ascorbic acid at 50
      ug/ml. The antiinflammatory activity of SEA is half of that of diclofenac at 50
      ug/ml. Anticancer activity was detected by measuring the mitochondrial
      dehydrogenase activity (MTT assay). The half maximal inhibitory concentrations
      (IC50) for MCF-7 and PC-3 cell lines are 250 and 700 ug/ml respectively. This was
      supported by the morphological changes such as membrane blebbing, cell detachment
      and rounded cell morphology when compared to the parental cells. In addition, we
      observed few green cells (live) over red cells (dead) based on the uptake of
      acridine orange and ethidium bromide dyes. Kaempferol-3-O-b-D-glucopyranoside, a
      Secondary metabolite of S.interrupta form 6 hydrogen bond interactions with Arg
      202, Gln 207, Gly 227, Gly 229, Thr 231 and Ala 232 human DEAD box RNA helicase,
      DDX3 protein and is equivalent to crystal structure of adenosine mono phosphate
      to DDX3. Overall, it suggests that the SEA extract has anticancer compounds, and
      it can be used to enhance death receptor mediated cancer cell death. 

PMID- 24748755
TI  - Virtual Screening of compounds from Tabernaemontana divaricata for potential anti
      bacterial activity.
AB  - Virtual Screening and Molecular Docking analysis for Tabernaemontana divaricata
      derived 66 Law Molecular Weight Compounds (LMW) was conducted and to identified
      and predicted novel molecules as a inhibitor of Streptococcus pneumonia. The
      investigation has revealed several compounds with optimum binding towards
      Penicillin-binding proteins, Sialidases, Aspartate betasemialdehide dehydrogenase
      cell membrane protein of Streptococcus pneumonia. Docking results were computed
      in term of binding energy, ligand efficiency and number of hydrogen bonding.
      Apparicine (-5.14), 5-Hydroxyvoaphylline (-4.78), Voacangine (-4.7), 19
      Hydroxycoronaridine (-4.44) and Coronaridine (-4.72) are identified as most
      suitable to bind with N-acetylglucosamine-1- phosphate uridyltransferase
      receptor. Ervaticine (-6.33), Ibogamine (-6.15), Methylvoaphylline (-5.74) and
      Coronaridine hydroxyindolenine (-5.32) has showed novel binding against the
      penicillin-binding proteins. Ervaticine (-6.42), 5-oxo-11-hydroxy voaphylline (
      6.18), Conolobine B (-6.02) has found optimum binding against the active site of
      NanB sialidase of Streptococcus pneumonia. The compounds 3S-Cyanocoronaridine (
      6.71), 19-Epivoacristine (-5.48) and Ervaticine(-5.45) interacting with aspartate
      beta-semialdehide and found suitable with least docking score. 

PMID- 24748756
TI  - Pharmacophore and Virtual Screening of JAK3 inhibitors.
AB  - Janus kinase 3 (JAK3) is a non-receptor tyrosine kinases family of protein which
      is comprised of JAK1, JAK2, JAK3 and TYK2. It plays an important role in immune
      function and lymphoid development and it only resides in the hematopoietic
      system. Therefore, selective targeting JAK3 is a rational approach in developing
      new therapeutic molecule. In this study, about 116 JAK3 inhibitors were collected
      from the literature and were used to build four-point pharmacophore model using
      Phase (Schrodinger module). The statistically significant pharmacophore
      hypothesis of AAHR.92 with r2 value of 0.942 was used as 3D query to search
      against 3D database namely Zincpharmer. A total of 2, 27,483 compounds obtained
      as hit were subjected to high throughput virtual screening (HTVS module of
      Schrodinger). Among the hits, ten compounds with good G-score ranging from -12.96
      to -11.18 with good binding energy to JAK3 were identified. 

PMID- 24748757
TI  - SBION: A Program for Analyses of Salt-Bridges from Multiple Structure Files.
AB  - Salt-bridge and network salt-bridge are specific electrostatic interactions that
      contribute to the overall stability of proteins. In hierarchical protein folding
      model, these interactions play crucial role in nucleation process. The advent and
      growth of protein structure database and its availability in public domain made
      an urgent need for context dependent rapid analysis of salt-bridges. While these
      analyses on single protein is cumbersome and time-consuming, batch analyses need
      efficient software for rapid topological scan of a large number of protein for
      extracting details on (i) fraction of salt-bridge residues (acidic and basic).
      (ii) Chain specific intra-molecular salt-bridges, (iii) inter-molecular salt
      bridges (protein-protein interactions) in all possible binary combinations (iv)
      network salt-bridges and (v) secondary structure distribution of salt-bridge
      residues. To the best of our knowledge, such efficient software is not available
      in public domain. At this juncture, we have developed a program i.e. SBION which
      can perform all the above mentioned computations for any number of protein with
      any number of chain at any given distance of ion-pair. It is highly efficient,
      fast, error-free and user friendly. Finally we would say that our SBION indeed
      possesses potential for applications in the field of structural and comparative
      bioinformatics studies. AVAILABILITY: SBION is freely available for non
      commercial/academic institutions on formal request to the corresponding author
      (akbanerjee@biotech.buruniv.ac.in).

PMID- 24748758
TI  - The effectiveness of four methods for stain removal from direct resin-based
      composite restorative materials.
AB  - BACKGROUND/PURPOSE: Few studies investigated the best method for removing stains
      from different types of resin-based composite restorations and compared them to
      the more recently introduced nanocomposites. This study compared the effect of
      four methods for stain removal from composite resins; finishing with Sof-lex
      disks, using pumice and brush, bleaching with 10% carbamide peroxide and 38%
      hydrogen peroxide. MATERIALS AND METHODS: Twenty disk specimens were prepared.
      Specimens were immersed in a staining solution for 3 weeks. The stained surfaces
      of five specimens from each RBC material were treated with one of the treatment
      procedures. Colorimetric measurements were taken using spectrophotometer prior to
      and after staining, and then repeated after surface treatments. Color difference
      values were calculated. RESULTS: One-way ANOVA indicated significant differences
      in color change of the three composite resin materials following staining. Filtek
      Z250 showed the least susceptibility to discoloration followed by Renamel, Filtek
      Supreme was the material most prone to discoloration. Two-way ANOVA and Tukey's
      Post Hoc showed that all stain removing procedures except polishing with pumice,
      were able to return Filtek Z250 to clinically acceptable color difference. While
      bleaching with 38% carbamide peroxide was not effective with Renamel. Only pumice
      and 10% carbamide peroxide were able to return Renamel to clinically acceptable
      color difference. CONCLUSION: Compositions of resin-based composite resins play
      an important role in their susceptibility to stain and their amenability to stain
      removal procedures. Home bleaching showed good results for the three materials,
      while office bleach was the least effective.

PMID- 24748759
TI  - Scoring from Contests.
AB  - This article presents a new model for scoring alternatives from "contest"
      outcomes. The model is a generalization of the method of paired comparison to
      accommodate comparisons between arbitrarily sized sets of alternatives in which
      outcomes are any division of a fixed prize. Our approach is also applicable to
      contests between varying quantities of alternatives. We prove that under a
      reasonable condition on the comparability of alternatives, there exists a unique
      collection of scores that produces accurate estimates of the overall performance
      of each alternative and satisfies a well-known axiom regarding choice
      probabilities. We apply the method to several problems in which varying choice
      sets and continuous outcomes may create problems for standard scoring methods.
      These problems include measuring centrality in network data and the scoring of
      political candidates via a "feeling thermometer." In the latter case, we also use
      the method to uncover and solve a potential difficulty with common methods of
      rescaling thermometer data to account for issues of interpersonal comparability.

PMID- 24748760
TI  - Association Between Follow-Up Magnetic Resonance Imaging and Clinical Status
      Among Patients With Spinal Infections.
AB  - BACKGROUND: Spinal infections, including paraspinal and/or epidural abscesses and
      vertebral discitis and osteomyelitis, can have devastating consequences. The
      diagnostic imaging modality of choice has traditionally been magnetic resonance
      imaging (MRI) given the very high sensitivity and specificity, although the role
      of MRI in follow-up of spinal infections and how this relates to follow-up
      clinical status is poorly understood. We sought to understand the relationship
      between follow-up MRI and clinical status. METHODS: We conducted a retrospective
      review of adults with spinal infection to assess the relationship between follow
      up MRI and clinical course. The degree of agreement between MRI and clinical
      follow-up was assessed using the Cohen kappa coefficient. A multinomial logistic
      regression model was applied to assess the impact of covariates in affecting the
      clinical outcome and MRI at follow-up independently. RESULTS: Ninety-eight
      patients met inclusion criteria during a 13-year period. We observed a lack of
      correlation between clinical follow-up status and MRI (kappa = 0.065, P = 0.322).
      The McNemar-Bowker test for symmetry revealed that this disagreement was
      asymmetric (P < 0.001). Notably, clinical worsening was never associated with an
      improved MRI, and clinical improvement was overall not predictive of MRI result
      and vice versa. CONCLUSIONS: Routine follow-up MRI does not seem to correlate
      with clinical follow-up among patients with spinal infections. The use of MRI
      without new clinical indications in routine follow-up testing should be
      interpreted with caution.

PMID- 24748761
TI  - Amygdala Activation and Emotional Processing in Adolescents at Risk for Substance
      Use Disorders.
AB  - Studies are needed that examine neurobiological characteristics in high risk
      individuals prior to substance use disorder (SUD) development. In this pilot
      study, 4 adolescent subjects at high risk (having at least 1 parent with a SUD)
      for SUD were compared with 4 adolescent reference subjects on a corticolimbic
      reactivity paradigm, where they were presented with affect-laden faces or
      geometric shapes. FMRI was used to measure cortical activation in response to
      these stimuli. High risk subjects, compared to low risk, exhibited greater left
      amygdala activation (t=3.60, df=6, p=0.01), suggesting they may exhibit hyper
      responsivity of the amygdala in response to emotional stimuli.

PMID- 24748762
TI  - THE HOPF BIFURCATION WITH BOUNDED NOISE.
AB  - We study Hopf-Andronov bifurcations in a class of random differential equations
      (RDEs) with bounded noise. We observe that when an ordinary differential equation
      that undergoes a Hopf bifurcation is subjected to bounded noise then the
      bifurcation that occurs involves a discontinuous change in the Minimal Forward
      Invariant set.

PMID- 24748763
TI  - Separation Differences Among Phenyl Hydride, UDC Cholesterol and Bidentate C8
      Stationary Phases for Stability Indicating Methods of Tetracyclines: Journal of
      Liquid Chromatography & Related Technologies.
AB  - Formulation extracts of tetracycline hydrochloride (HCl), minocycline
      hydrochloride (HCl), and doxycycline hyclate were degraded by strong acidic
      conditions and heating. Subsequently, components of the extracts were separated
      by Bidentate C8, Phenyl Hydride and Cholesterol (UDC) HPLC columns operating in
      the reverse phase mode. The Phenyl Hydride column was able to baseline separate
      minocycline from the observed degradant, while partial or total co-elution was
      observed with the other two columns using otherwise identical method conditions.
      For both the degraded tetracycline HCl and doxycycline hyclate extracts, the UDC
      column gave the best resolution for the critical pair. The findings suggest that
      the postulated secondary retention mechanisms of pi-pi interactions from the
      Phenyl Hydride and shape selectivity from the UDC can provide superior resolution
      for structurally similar analytes compared to hydrophobic interactions alone.

PMID- 24748764
TI  - Improved contrast and spatial resolution with Single Photon Counting (SPC) for an
      area x-ray imager, the newly developed high-resolution Micro-Angiographic
      Fluoroscopic (MAF) detector.
AB  - Although in radiological imaging, the prevailing mode of acquisition is the
      integration of the energy deposited by all x-rays absorbed in the imaging
      detector, much improvement in image spatial and contrast resolution could be
      achieved if each individual x-ray photon were detected and counted separately. In
      this work we compare the conventional energy integration (EI) mode with the new
      single photon counting (SPC) mode for a recently developed high-resolution Micro
      Angiographic Fluoroscopic (MAF) detector, which is uniquely capable of both modes
      of operation. The MAF has 1024*1024 pixels of 35 microns effective size and is
      capable of real-time imaging at 30 fps. The large variable gain of its light
      image intensifier (LII) provides quantum limited operation with essentially no
      additive instrumentation noise and enables the MAF to operate in both EI and the
      very sensitive low-exposure SPC modes. We used high LII gain with very low
      exposure (<1 x-ray photon/pixel) per frame for SPC mode and higher exposure per
      frame with lower gain for EI mode. Multiple signal-thresholded frames were summed
      in SPC mode to provide an integrated frame with the same total exposure as EI
      mode. A heavily K-edge filtered x-ray beam (average energy of 31 keV) was used to
      provide a nearly monochromatic spectrum. The MTF measured using a standard slit
      method showed a dramatic improvement for the SPC mode over the EI mode at all
      frequencies. Images of a line pair phantom also showed improved spatial
      resolution with 12 lp/mm visible in SPC mode compared to only 8 lp/mm in EI mode.
      In SPC mode, images of human distal and middle phalanges showed the trabecular
      structures of the bone with far better contrast and detail. These improvements
      with the SPC mode should be advantageous for clinical applications where high
      resolution and/or high contrast are essential such as in mammography and
      extremity imaging as well as for dual modality applications, which combine
      nuclear medicine and x-ray imaging using a single detector.

PMID- 24748765
TI  - Incidence rate and occurrence of visually significant cataract formation and
      corneal decompensation after implantation of Verisyse/Artisan phakic intraocular
      lens.
AB  - PURPOSE: To evaluate the incidence rate and indications for explantation of
      Verisyse phakic intraocular lenses (pIOLs) over a 13.6 year period. SUBJECTS AND
      METHODS: Case series describing six cases of explantation of Verisyse pIOLs, out
      of 213 eyes with Verisyse pIOLs, implanted over a 13.6 year period by one surgeon
      at one institution, with mean follow-up of 5.6 years per eye. RESULTS: Four pIOLs
      were removed to facilitate extraction of a visually significant cataract, one was
      removed due to both cataract formation and development of corneal decompensation,
      and another was removed due to development of localized peripheral corneal
      decompensation. The incidence rate of pIOL removal was five per 1,000 patient
      years with pIOL. Mean time from insertion of pIOL to cataract removal was 9.3
      years (range 4.0-12.6 years). Mean time from insertion of pIOL to development of
      corneal decompensation was 10 years (range 6.9-13 years). There was no increase
      in the rate of cataract extraction in the pIOL population compared to the general
      population. CONCLUSION: Cataracts may develop in patients with pIOLs,
      necessitating removal of the pIOL. Corneal decompensation is a serious
      complication that appears to be directly related to pIOLs. Corneal decompensation
      can occur up to 13 years following implantation of pIOLs, and long-term follow-up
      is important to monitor for this complication.

PMID- 24748766
TI  - Bilateral visual outcomes and service utilization of patients treated for 3 years
      with ranibizumab for neovascular age-related macular degeneration.
AB  - BACKGROUND: The aim of this study was to describe bilateral visual outcomes and
      the effect of incomplete follow-up after 3 years of ranibizumab therapy for
      neovascular age-related macular degeneration. Secondarily, the demands on service
      provision over a 3-year period were described. METHODS: Data on visual acuity,
      hospital visits, and injections were collected over 36 months on consecutive
      patients commencing treatment over a 9-month period. Visual outcome was
      determined for 1) all patients, using last observation carried forward for missed
      visits due to early discontinuation and 2) only those patients completing full 36
      month follow-up. RESULTS: Over 3 years, 120 patients cumulatively attended
      hospital for 1,823 noninjection visits and 1,365 injection visits. A visual
      acuity loss of <15 letters (L) was experienced by 78.2% of patients. For all
      patients (n=120), there was a mean loss of 1.68 L using last observation carried
      forward for missing values. Excluding five patients who died and 30 who
      discontinued follow-up, mean gain was 1.47 L. In bilateral cases, final acuity
      was on average 9 L better in second eyes compared to first eyes. Also, 91% of
      better-seeing eyes continued to be the better-seeing eye. CONCLUSION: We have
      demonstrated our approach to describing the long-term service provision and
      visual outcomes of ranibizumab therapy for neovascular age-related macular
      degeneration in a consecutive cohort of patients. Although there was a heavy
      burden with very frequent injections and clinic visits, patients can expect a
      good level of visual stability and a very high chance of maintaining their better
      seeing eye for up to 3 years.

PMID- 24748767
TI  - Bimatoprost/timolol fixed combination versus latanoprost in treatment-naive
      glaucoma patients at high risk of progression: a pilot study.
AB  - OBJECTIVE: To compare a fixed combination of 0.03% bimatoprost and 0.5% timolol
      (BTFC) with latanoprost monotherapy (LM) in treatment-naive patients with open
      angle glaucoma (OAG) and risk factors for glaucomatous progression. METHODS:
      Patients were enrolled at 15 sites in Spain and Portugal, and were randomized 1:1
      to BTFC or LM. Patients instilled one drop of medication once per day at 8 pm for
      12 weeks. The primary outcome was change in intraocular pressure (IOP) at 12
      weeks. RESULTS: Of 81 patients enrolled, 43 were randomized to BTFC and 38 to LM.
      Mean (SD) change in IOP from baseline to 12 weeks was significantly greater for
      BTFC than for LM: -13.5 mmHg (4.48) versus -11.4 mmHg (3.19), respectively
      (P=0.003). Similarly, at 12 weeks, significantly more BTFC patients than LM
      patients had IOP reductions of >=40% (74.4% versus 47.4%, P=0.015) or >=50%
      (46.5% versus 15.8%, P=0.003). Adverse events were more frequent with BTFC than
      with LM (33 versus 13 events), but most were mild in severity. The only serious
      adverse event (colon cancer) was adjudged unrelated to the study medication.
      CONCLUSION: BTFC was effective and well tolerated in treatment-naive patients
      with OAG at high risk of progression.

PMID- 24748768
TI  - Sequential bilateral retinal artery occlusion.
AB  - An 86 year old woman experienced a sequential bilateral loss of vision over a
      period of less than 24 hours. Clinical findings and complementary studies
      suggested a bilateral atherogenic embolic event. Initially, she presented a
      superior branch retinal artery occlusion in her right eye followed by a central
      retinal artery occlusion with cilioretinal artery sparing in her left eye. Some
      conservative maneuvers performed did not improve visual acuity in the left eye.
      Supra-aortic Doppler ultrasonography revealed mild right internal carotid artery
      stenosis and moderate left internal carotid artery stenosis with a small, smooth,
      and homogeneous plaque. The transthoracic echocardiography showed a severe
      calcification of the mitral valve with a mild-moderate rim of stenosis. Central
      retinal artery occlusion and branch retinal artery occlusion are characterized by
      painless monocular loss of vision. Clinical approach and management attempt to
      treat the acute event, find the source of the vascular occlusion, and prevent
      further vascular events from occurring. Giant cell arteritis is a potentially
      treatable cause of central retinal artery occlusion and should be excluded in
      every single patient over 50 years old. 

PMID- 24748769
TI  - Evaluation of intraocular pressure elevation after multiple injections of
      intravitreal ranibizumab.
AB  - BACKGROUND: We wanted to determine whether multiple injections of intravitreal
      ranibizumab was associated with an elevated intraocular pressure (IOP) in
      patients treated for neovascular age-related macular degeneration (AMD). METHODS:
      This retrospective study examined 53 patients with neovascular AMD treated with
      multiple injections of intravitreal ranibizumab. The main outcome measure was the
      difference in IOP between the frequently-treated study eyes (>=15 injections) and
      the unfrequently-treated fellow control eyes (<= five injections). Patients were
      divided into three study groups: group I (35 patients with 15 to 19 injections);
      group II (15 patients with 20 to 29 injections); and group III (three patients
      with >=30 injections). The IOP was measured by Goldmann applanation tonometry 4
      weeks after the last injection of intravitreal ranibizumab. For statistical
      analysis, the IOP was then correlated with the number of ranibizumab injections.
      RESULTS: Among the frequently-treated study eyes, the mean IOP was 13.68+/-2.91
      mmHg (range, 8 to 20 mmHg). The unfrequently-treated fellow control eyes had a
      mean IOP of 13.45+/-3.09 mmHg (range, 9 to 25 mmHg). There was no significant
      correlation of the IOP difference between the study and control eyes with the
      number of ranibizumab injections (correlation coefficient 0.77; P=0.583). For
      each of groups I, II, and III, the difference in mean IOP between the study and
      control eyes was nonsignificant (P>0.05). There was also no significant
      association of the IOP difference between the study and control eyes with the
      number of ranibizumab injections for each group (P=0.391). CONCLUSION: Our study
      did not find an increased IOP in frequently-ranibizumab-treated eyes when
      compared to unfrequently-treated fellow control eyes. Further studies with a
      greater sample size are needed to evaluate whether an increased number of
      ranibizumab injections is associated with IOP changes.

PMID- 24748770
TI  - Peripapillary retinal nerve fiber layer and foveal thickness in hypermetropic
      anisometropic amblyopia.
AB  - PURPOSE: To evaluate whether there was a difference in peripapillary retinal
      nerve fiber layer (RNFL) and foveal thickness between amblyopic and normal
      individuals with optical coherence tomography. MATERIALS AND METHODS: Sixty
      patients, 30 patients with hypermetropic anisometropic amblyopia and 30 normal
      emmetropic subjects, were enrolled in this study. The eyes of the participants
      were divided into three groups: 30 eyes of 30 patients with amblyopia (A), 30
      fellow eyes of the amblyopic patients (B), and 30 eyes of 30 normal subjects (C).
      Emmetropic normal subjects included cases with normal visual acuity and
      unremarkable ocular examinations. After routine ophthalmic examination,
      peripapillary retinal nerve fiber layer and foveal thickness measurements were
      measured by time-domain optical coherence tomography and compared among the three
      groups. RESULTS: The difference in RNFL thickness between amblyopic eyes, fellow
      eyes of the amblyopic patients, and normal eyes of the emmetropic subjects was
      not clinically significant. However, the mean foveal thickness was significantly
      thicker in amblyopic eyes versus the fellow eyes and normal subjects' eyes.
      CONCLUSION: Our results suggest that amblyopia seems to have an effect on the
      foveal thickness, but not on the RNFL thickness.

PMID- 24748771
TI  - Multikinase inhibitors in the treatment of thyroid cancer: specific role of
      lenvatinib.
AB  - Thyroid cancers are the most frequent neoplasms of the endocrine system and in
      the initial stages their prognosis is excellent. However, few therapeutic options
      are available for advanced or metastatic disease. In the last decade, a better
      understanding of the molecular events involved in the tumorigenesis of thyroid
      cancers has led to development of new targeted agents for the management of
      advanced and refractory disease. Multikinase inhibitors that are able to block
      pathways involved in the proliferation, invasion, and neoangiogenesis of thyroid
      cancer have been the most widely studied. After an international effort to
      identify and recruit sufficient patients, four placebo-controlled studies of
      multikinase inhibitors have been completed. These trials have led to the approval
      of the first agents with activity in advanced medullary thyroid cancers, which
      will probably change the landscape of treatment for iodine-refractory
      differentiated thyroid cancer in the near future. The purpose of this paper is to
      review the development of targeted agents for thyroid malignancy, with a special
      focus on lenvatinib, a multikinase inhibitor. 

PMID- 24748772
TI  - Triazole derivatives with improved in vitro antifungal activity over azole drugs.
AB  - A series of triazole antifungal agents with piperidine side chains was designed
      and synthesized. The results of antifungal tests against eight human pathogenic
      fungi in vitro showed that all the compounds exhibited moderate-to-excellent
      activities. Molecular docking between 8d and the active site of Candida albicans
      CYP51 was provided based on the computational docking results. The triazole
      interacts with the iron of the heme group. The difluorophenyl group is located in
      the S3 subsite and its fluorine atom (2-F) can form H-bonds with Gly307. The side
      chain is oriented into the S4 subsite and formed hydrophobic and van der Waals
      interactions with the amino residues. Moreover, the phenyl group in the side
      chain interacts with the phenol group of Phe380 through the formation of pi-pi
      face-to-edge interactions.

PMID- 24748773
TI  - Quality of life in elderly patients following coronary artery bypass grafting.
AB  - BACKGROUND: Surgical revascularization of the coronary arteries leads to changes
      in quality of life (QoL) for patients with coronary heart disease. The aim of
      this work was to monitor QoL, considering cognitive function, depression, and
      activities of daily living in elderly patients after coronary artery bypass
      grafting (CABG). METHODS: This study included 65 patients (29 women and 36 men)
      aged 61-74 years with stable coronary heart disease who underwent CABG. The
      control group included 29 women and 36 men aged 61-74 years who were not
      suffering from coronary heart disease. The questionnaires used in the study
      canvassed QoL (Nottingham Health Profile), cognitive function, depression, and
      basic and instrumental activities of daily living. The research was conducted
      before surgery and repeated 6 and 12 months after surgery. RESULTS: QoL was
      comparable between women and men and was lower than in the control group
      (P<0.05). After CABG, the values for particular domains of QoL improved more in
      men than in women. There was a reduction in the severity of depression 6 months
      after surgery in men and 12 months after surgery in women. CONCLUSION: Elderly
      patients with coronary heart disease have decreased QoL, which normalizes in men
      and improves in women after CABG.

PMID- 24748774
TI  - Cancer-associated thrombosis, low-molecular-weight heparin, and the patient
      experience: a qualitative study.
AB  - BACKGROUND: Venous thromboembolism is a common complication of cancer and its
      treatments. Treatment of cancer-associated thrombosis (CAT) differs from
      treatment of thrombosis in noncancer patients, requiring a daily injection of low
      molecular-weight heparin (LMWH) for 6 months instead of an oral anticoagulant.
      Previous research suggested LMWH is an acceptable intervention in the treatment
      of CAT, yet clinical practice and therapeutic opportunities have changed in the
      decade since the study was conducted. Furthermore, in the previous study there
      was acknowledged selection bias in participant recruitment. There is increasing
      clinical use of the novel oral anticoagulants, although their efficacy and safety
      is yet to be demonstrated within the cancer population. The experience of
      patients receiving anticoagulation for CAT will inform future practice with
      respect to quality of life and adherence to anticoagulation therapy. AIM: To
      explore the acceptability of long-term LMWH for the treatment of CAT in the
      contexts of living with cancer and quality of life. DESIGN: Qualitative study of
      cancer patients who had been receiving LMWH for at least 3 months for CAT was
      undertaken. Audiotaped semistructured interviews were conducted and transcribed.
      Thematic analysis was undertaken until theoretical saturation.
      SETTING/PARTICIPANTS: Fourteen patients attending a palliative care or CAT clinic
      were interviewed. Participants had been receiving LMWH for a median 6 months.
      RESULTS: Participants reported distressing symptoms associated with symptomatic
      CAT, which they rated as worse than their cancer experiences. LMWH was considered
      an acceptable intervention despite challenges of long-term injections. Several
      adaptive techniques were reported to optimize ongoing injections. Participants
      would only favor a novel oral anticoagulant if it was equivalent to LMWH in
      efficacy and safety. CONCLUSION: Although LMWH remains an acceptable intervention
      for the treatment of CAT, its long-term use is associated with bruising and
      deterioration of injection sites. These are considered an acceptable trade-off
      against their strongly negative experiences of symptomatic venous
      thromboembolism.

PMID- 24748776
TI  - Curing a 96-year-old patient afflicted with benign paroxysmal positional vertigo
      on a motorized turntable.
AB  - BACKGROUND: Dizziness in the elderly is a serious health concern due to the
      increased morbidity caused by falling. The most common cause of dizziness in the
      elderly, benign paroxysmal positional vertigo (BPPV), is frequently undiagnosed,
      and bedside treatment of these patients can be difficult due to neck and back
      stiffness, which makes repeated and accurate repositioning maneuvers difficult.
      CASE PRESENTATION: After a fall, a 96-year-old woman was referred by a resident
      neurologist for intractable BPPV. The patient was placed on a motorized turntable
      and repositioned to remove the calcite particles from the affected posterior
      semicircular canal. Video monitoring of the eyes allowed confirmation of the
      diagnosis, as well as an immediate evaluation of the effectiveness of the
      maneuver. CONCLUSION: Every patient with dizziness or imbalance, even in the
      absence of typical complaints of BPPV, should be tested with provocation
      maneuvers, because the clinical picture of BPPV is not always typical. Even if
      elderly patients with dizziness are very frail, the completion of provocation
      maneuvers is imperative, since the therapeutic maneuvers are extremely effective.
      A motorized turntable is very helpful to perform the repositioning accurately and
      safely.

PMID- 24748775
TI  - A review of denosumab for the treatment of osteoporosis.
AB  - Osteoporosis is an age-related systemic skeletal disease characterized by low
      bone mass and microarchitectural deterioration of bone tissue, with a consequent
      increase in bone fragility. Bone remodeling involves two types of cells:
      osteoblasts and osteoclasts. Receptor activator of nuclear factor-kappaB ligand
      (RANKL) is a key regulator of the formation and function of bone-resorbing
      osteoclasts, and its cell surface receptor, receptor activator of nuclear factor
      kappaB (RANK), is expressed by both osteoclast precursors and mature osteoclasts.
      Denosumab is a fully human monoclonal anti-RANKL antibody that inhibits the
      binding of RANKL to RANK, thereby decreasing osteoclastogenesis and bone
      resorbing activity of mature osteoclasts. Although there are many medications
      available for the treatment of osteoporosis, inhibition of RANKL by denosumab has
      been shown to significantly affect bone metabolism. Denosumab appears to be a
      promising, highly effective, and safe parenteral therapy with good adherence for
      osteoporosis. Moreover, denosumab may be cost-effective therapy compared with
      existing alternatives. Therefore, in this review, we focus on studies of
      denosumab and the risks and benefits identified for this type of treatment for
      osteoporosis. 

PMID- 24748777
TI  - Osteoporosis in men: epidemiology and treatment with denosumab.
AB  - Osteoporosis is a major public health care concern. Although often described as a
      disease affecting postmenopausal women, researchers and clinicians have
      emphasized its prevalence in men in recent years. The National Osteoporosis
      Foundation has stated that up to 25% of men over the age of 50 years will
      experience a fracture due to osteoporosis. Men who suffer from a major fracture
      have higher mortality rates than women. Pharmacologic therapy options for
      treating osteoporosis are limited for men as compared with women, so each
      medication approved for use in this population represents an important clinical
      option. In September 2012, the US Food and Drug Administration approved a new
      indication for denosumab to increase bone mass in men with osteoporosis at high
      risk for fracture. Denosumab is a fully human monoclonal antibody and novel
      antiresorptive agent that works by binding receptor activator of nuclear factor
      kappa-beta ligand (RANKL) and inhibiting the signaling cascade that causes
      osteoclast maturation, activity, and survival. Ultimately, denosumab suppresses
      bone turnover and increases bone mineral density in both trabecular and cortical
      bone. Approval for treating osteoporosis in men was based on data from the ADAMO
      trial which displayed efficacy in increasing bone mineral density at the lumbar
      spine, total hip, femoral neck, hip trochanter, and one-third radius. Studies
      indicate that denosumab is effective and safe, and has superior adherence rates
      and patient satisfaction. Although long-term data and further research on
      fracture reduction rates in men should be explored, at this time denosumab is one
      of several appropriate first-line treatment options for men with osteoporosis. 

PMID- 24748778
TI  - Outcomes of an innovative model of acute delirium care: the Geriatric Monitoring
      Unit (GMU).
AB  - OBJECTIVE: Delirium is associated with poor outcomes following acute
      hospitalization. The Geriatric Monitoring Unit (GMU) is a specialized five-bedded
      unit for acute delirium care. It is modeled after the Delirium Room program, with
      adoption of core interventions from the Hospital Elder Life Program and use of
      evening light therapy to consolidate circadian rhythms and improve sleep in older
      inpatients. This study examined whether the GMU program improved outcomes in
      delirious patients. METHOD: A total of 320 patients, including 47 pre-GMU, 234
      GMU, and 39 concurrent control subjects, were studied. Clinical characteristics,
      cognitive status, functional status (Modified Barthel Index [MBI]), and chemical
      restraint-use data were obtained. We also looked at in-hospital complications of
      falls, pressure ulcers, nosocomial infection rate, and discharge destination.
      Secondary outcomes of family satisfaction (for the GMU subjects) were collected.
      RESULTS: There were no significant demographic differences between the three
      groups. Pre-GMU subjects had longer duration of delirium and length of stay. MBI
      improvement was most evident in the GMU compared with pre-GMU and control
      subjects (19.2+/-18.3, 7.5+/-11.2, 15.1+/-18.0, respectively) (P<0.05). The GMU
      subjects had a zero restraint rate, and pre-GMU subjects had higher antipsychotic
      dosages. This translated to lower pressure ulcer and nosocomial infection rate in
      the GMU (4.1% and 10.7%, respectively) and control (1.3% and 7.7%, respectively)
      subjects compared with the pre-GMU (9.1% and 23.4%, respectively) subjects
      (P<0.05). No differences were observed in mortality or discharge destination
      among the three groups. Caregivers of GMU subjects felt the multicomponent
      intervention to be useful, with scheduled activities voted the most beneficial in
      patient's recovery from the delirium episode. CONCLUSION: This study shows the
      benefits of a specialized delirium management unit for older persons. The GMU
      model is thus a relevant system of care for rapidly "graying" nations with high
      rates of frail elderly hospital admissions, which can be easily transposed across
      acute care settings.

PMID- 24748779
TI  - Help-seeking preferences in the area of mild cognitive impairment: comparing
      family physicians and the lay public.
AB  - BACKGROUND: Mild cognitive impairment (MCI) or mild neurocognitive disorder is a
      well-established clinical entity included in current diagnostic guidelines for
      Alzheimer's disease and in major psychiatric classifications. In all, a loosely
      defined concern obtained from conceptually different sources (the individual, a
      knowledgeable informant, or a clinician) regarding a decline in cognition and
      change in functioning constitutes a sine qua non for initiating diagnostics and
      providing therapy and support. This concern in practice may translate into
      complex proactive help-seeking behavior. A better understanding of help-seeking
      preferences is required in order to promote early detection and management.
      OBJECTIVES: To compare help-seeking preferences of family physicians and the lay
      public in the area of MCI. METHODS: A structured questionnaire was used to
      collect data from 197 family physicians (self-administered) and 517 persons aged
      45 and over from the lay public (face to face). Information regarding familiarity
      with MCI and help-seeking preferences was assessed. RESULTS: The vast majority in
      both samples reported that family physician, spouse, and children are the most
      highly recommended sources of help-seeking. In regard to professional sources of
      help-seeking, a higher percentage of the physicians than the lay public sample
      consistently recommended seeking help from nurses and social workers and
      psychiatrists, but a higher percentage of the lay public recommended turning to a
      neurologist for help. DISCUSSION: There were both similarities and differences
      between family physicians and the lay public in their preferences regarding help
      seeking for a person with MCI. Most prominent is the physicians' greater tendency
      to recommend professional sources of help-seeking. CONCLUSION: Understanding of
      help-seeking preferences of both physicians and lay persons might help overcome
      barriers for establishing diagnosis, receiving care, and improving communication
      between doctors and patients.

PMID- 24748780
TI  - Public-private partnerships improve health outcomes in individuals with early
      stage Alzheimer's disease.
AB  - PURPOSE: In a collaborative effort between the Missouri Department of Health,
      Area Agencies on Aging (AAA), Alzheimer Association, and academic researchers, we
      tested whether early dementia detection and comprehensive care consultations
      would improve health outcomes in care receivers (CRs) and their family caregivers
      (FCGs), therefore addressing an important public health concern. PARTICIPANTS AND
      METHODS: A total of 244 community-dwelling older adults screened for early-stage
      dementia by the AAA field staff were referred to the Alzheimer Association and
      participated in Project Learn MORE (Missouri Outreach and Referral Expanded)
      (PLM) - a 2-year, nonrandomized multisite intervention consisting of
      comprehensive care consultations to improve coping skills. PLM participants were
      compared against 96 controls receiving the Alzheimer Association's "usual
      services" between January 2011 and December 2012. We examined CR and FCG
      outcomes, including burden, care confidence, and mood, as effects of PLM, on
      delaying transitions in level of care. RESULTS: CRs showed improved knowledge
      (P=0.002) and reduced depression (P=0.007), while FCGs demonstrated improved
      knowledge (P=0.003) and ability to identify sources of support for the CR
      (P=0.032) and for themselves (P=0.043). However, FCGs were more burdened after
      PLM (P=0.02), due to increased awareness of Alzheimer's disease. PLM delayed
      transitions in care (odds ratio [OR] 3.32, 95% confidence level [CI]: 1.25-8.83)
      with the number needed to treat =6.82. CONCLUSION: PLM was successful in
      improving detection of incident cases of dementia in the community and in
      connecting patients and their families with needed services. Our findings support
      the use of state agencies and community service partners to detect dementia.
      Early implementation of psychosocial interventions could have significant impact
      in improving patient- and family-centered outcomes, potentially providing a cost
      efficient alternative to pharmacotherapy.

PMID- 24748781
TI  - Effectiveness of online cognitive behavioral therapy on family caregivers of
      people with dementia.
AB  - PURPOSE: Family caregivers of persons with dementia (PWD) may receive caregiver
      training because of logistical constraints and privacy concerns. This study
      evaluated the effectiveness of an online intervention for family caregivers of
      PWD in improving their self-efficacy in managing behavioral and psychological
      symptoms of dementia (BPSD), and their emotion well-being. SUBJECTS AND METHODS:
      A total of 36 family caregivers of people with dementia participated in a 9-week
      online intervention based on the cognitive behavioral therapy model. Outcomes of
      the intervention were measured by the Chinese version of the Neuropsychiatric
      Inventory Questionnaire and two domains of the Revised Scale for Caregiving Self
      Efficacy. Wilcoxon signed rank tests were used to compare the change in outcome
      variables. RESULTS: The severity of BPSD of PWD and BPSD-related distress in
      family caregivers showed a statistically significant reduction after the
      intervention. Subgroup analysis showed self-efficacy in controlling upsetting
      thoughts significantly improved in caregivers of PWD at moderate to severe
      stages. CONCLUSION: Online cognitive behavioral therapy for family caregivers
      reduced BPSD of PWD and the related distress in their caregivers.

PMID- 24748783
TI  - Changes in spinal range of motion after a flexibility training program in elderly
      women.
AB  - BACKGROUND: Aging-related reduced spinal mobility can interfere with the
      execution of important functional skills and activities in elderly women.
      Although several studies have shown positive outcomes in response to spinal
      flexibility training programs, little is known about the management of sets and
      repetitions in training protocols. The purpose of this study was to investigate
      the effects of an 8-week specific and standardized flexibility training program
      on the range of spinal motion in elderly women. METHODS: PARTICIPANTS WERE
      RECRUITED IN A SENIOR CENTER OF PALERMO AND RANDOMLY ASSIGNED IN TWO GROUPS:
      trained group (TG) and control group (CG), which included 19 and 18 women,
      respectively. TG was trained for 8 weeks at two sessions/week. In particular,
      every session included three phases: warm up (~10 minutes), central period (~50
      minutes), and cool down (~10 minutes). CG did not perform any physical activity
      during the experimental period. Spinal ranges of motion (ROM) were measured from
      neutral standing position to maximum bending position and from neutral standing
      position to maximum extension position before and after the experimental period,
      using a SpinalMouse(r) device (Idiag, Volkerswill, Switzerland). RESULTS: After
      the training period, TG showed an increase in spinal inclination by 16.4%
      (P<0.05), in sacral/hip ROM by 29.2% (P<0.05), and in thoracic ROM by 22.5%
      (P>0.05) compared with CG from maximum extension position to maximum bending
      position. We did not observe any significant difference in TG's lumbar ROM
      compared with CG after the training period (P>0.05). CONCLUSION: We found that an
      8-week flexibility training program improved ROMs of the spine in elderly women.
      The training protocol appeared to be practicable for active elderly people with
      autonomy and the capability for self-care.

PMID- 24748782
TI  - Oxidative stress and its downstream signaling in aging eyes.
AB  - BACKGROUND: Oxidative stress (OS) and its biomarkers are the biochemical end
      point of the imbalance between reactive oxygen species (ROS) production and the
      ability of the antioxidant (AOX) biological systems to fight against oxidative
      injury. OBJECTIVE: We reviewed the role of OS and its downstream signaling in
      aging eyes. METHODS: A search of the literature and current knowledge on the
      physiological and pathological mechanisms of OS were revisited in relation to the
      eyes and the aging process. Most prevalent ocular diseases have been analyzed
      herein in relation to OS and nutraceutic supplements, such as dry-eye disorders,
      glaucoma, age-related macular degeneration, and diabetic retinopathy. RESULTS:
      Clinical, biochemical, and molecular data from anterior and posterior eye segment
      diseases point to OS as the common pathogenic mechanism in the majority of these
      ocular disorders, many of which are pathologies causing visual impairment,
      blindness, and subsequent loss of life quality. Studies with nutraceutic
      supplements in aging eye-related pathologies have also been reviewed. CONCLUSION:
      OS, nutritional status, and nutraceutic supplements have to be considered within
      the standards of care of older ophthalmologic patients. OS biomarkers and
      surrogate end points may help in managing the aging population with ocular
      diseases.

PMID- 24748784
TI  - Physical activity and cognitive function in individuals over 60 years of age: a
      systematic review.
AB  - BACKGROUND: It is unclear whether physical activity in later life is beneficial
      for maintenance of cognitive function. We performed a systematic review examining
      the effects of exercise on cognitive function in older individuals, and present
      possible mechanisms whereby physical activity may improve cognition. METHODS:
      Sources consisted of PubMed, Medline, CINAHL, the Cochrane Controlled Trials
      Register, and the University of Washington, School of Medicine Library Database,
      with a search conducted on August 15, 2012 for publications limited to the
      English language starting January 1, 2000. Randomized controlled trials including
      at least 30 participants and lasting at least 6 months, and all observational
      studies including a minimum of 100 participants for one year, were evaluated. All
      subjects included were at least 60 years of age. RESULTS: Twenty-seven studies
      met the inclusion criteria. Twenty-six studies reported a positive correlation
      between physical activity and maintenance or enhancement of cognitive function.
      Five studies reported a dose-response relationship between physical activity and
      cognition. One study showed a nonsignificant correlation. CONCLUSION: The
      preponderance of evidence suggests that physical activity is beneficial for
      cognitive function in the elderly. However, the majority of the evidence is of
      medium quality with a moderate risk of bias. Larger randomized controlled trials
      are needed to clarify the association between exercise and cognitive function and
      to determine which types of exercise have the greatest benefit on specific
      cognitive domains. Despite these caveats, the current evidence suggests that
      physical activity may help to improve cognitive function and, consequently, delay
      the progression of cognitive impairment in the elderly.

PMID- 24748785
TI  - Explaining the increased health care expenditures associated with
      gastroesophageal reflux disease among elderly Medicare beneficiaries with chronic
      obstructive pulmonary disease: a cost-decomposition analysis.
AB  - OBJECTIVE: To estimate excess health care expenditures associated with
      gastroesophageal reflux disease (GERD) among elderly individuals with chronic
      obstructive pulmonary disease (COPD) and examine the contribution of predisposing
      characteristics, enabling resources, need variables, personal health care
      practices, and external environment factors to the excess expenditures, using the
      Blinder-Oaxaca linear decomposition technique. METHODS: This study utilized a
      cross-sectional, retrospective study design, using data from multiple years (2006
      2009) of the Medicare Current Beneficiary Survey linked with fee-for-service
      Medicare claims. Presence of COPD and GERD was identified using diagnoses codes.
      Health care expenditures consisted of inpatient, outpatient, prescription drugs,
      dental, medical provider, and other services. For the analysis, t-tests were used
      to examine unadjusted subgroup differences in average health care expenditures by
      the presence of GERD. Ordinary least squares regressions on log-transformed
      health care expenditures were conducted to estimate the excess health care
      expenditures associated with GERD. The Blinder-Oaxaca linear decomposition
      technique was used to determine the contribution of predisposing characteristics,
      enabling resources, need variables, personal health care practices, and external
      environment factors, to excess health care expenditures associated with GERD.
      RESULTS: Among elderly Medicare beneficiaries with COPD, 29.3% had co-occurring
      GERD. Elderly Medicare beneficiaries with COPD/GERD had 1.5 times higher ($36,793
      vs $24,722 [P<0.001]) expenditures than did those with COPD/no GERD. Ordinary
      least squares regression revealed that individuals with COPD/GERD had 36.3%
      (P<0.001) higher expenditures than did those with COPD/no GERD. Overall, 30.9% to
      43.6% of the differences in average health care expenditures were explained by
      differences in predisposing characteristics, enabling resources, need variables,
      personal health care practices, and external environment factors between the two
      groups. Need factors explained up to 41% of the differences in average health
      care expenditures between the two groups. CONCLUSION: Among elderly Medicare
      beneficiaries with COPD, the presence of GERD was associated with higher
      expenditures. Need factors primarily contributed to the differences in average
      health care expenditures, suggesting that the comanagement of chronic conditions
      may reduce excess health care expenditures associated with GERD.

PMID- 24748787
TI  - In vivo MR detection of fluorine-labeled human MSC using the bSSFP sequence.
AB  - Mesenchymal stem cells (MSC) are used to restore deteriorated cell environments.
      There is a need to specifically track these cells following transplantation in
      order to evaluate different methods of implantation, to follow their migration
      within the body, and to quantify their accumulation at the target. Cellular
      magnetic resonance imaging (MRI) using fluorine-based nanoemulsions is a great
      means to detect these transplanted cells in vivo because of the high specificity
      for fluorine detection and the capability for precise quantification. This
      technique, however, has low sensitivity, necessitating improvement in MR
      sequences. To counteract this issue, the balanced steady-state free precession
      (bSSFP) imaging sequence can be of great interest due to the high signal-to-noise
      ratio (SNR). Furthermore, it can be applied to obtain 3D images within short
      acquisition times. In this paper, bSSFP provided accurate quantification of
      samples of the perfluorocarbon Cell Sense-labeled cells in vitro. Cell Sense was
      internalized by human MSC (hMSC) without adverse alterations in cell viability or
      differentiation into adipocytes/osteocytes. The bSSFP sequence was applied in
      vivo to track and quantify the signals from both Cell Sense-labeled and iron
      labeled hMSC after intramuscular implantation. The fluorine signal was observed
      to decrease faster and more significantly than the volume of iron-associated
      voids, which points to the advantage of quantifying the fluorine signal and the
      complexity of quantifying signal loss due to iron. 

PMID- 24748786
TI  - Update on obstructive sleep apnea and its relation to COPD.
AB  - Chronic obstructive pulmonary disease (COPD) is a common and preventable lung
      disease that affects millions of people in the United States. Sleep disorders
      including obstructive sleep apnea (OSA) are also common. It is not surprising
      that many people with COPD also suffer from OSA. This relationship, however, puts
      people at risk for more nocturnal desaturations and potential complications
      related to this, including pulmonary hypertension and heart rhythm disturbances.
      This update focuses on the physiology of sleep disturbances in COPD as well as
      the clinical implications of OSA in COPD. 

PMID- 24748788
TI  - Multifunctional nanosystems: growing sanguinity in siRNA therapy.

PMID- 24748789
TI  - Decreased Staphylococcus aureus and increased osteoblast density on
      nanostructured electrophoretic-deposited hydroxyapatite on titanium without the
      use of pharmaceuticals.
AB  - BACKGROUND: Plasma-spray deposition of hydroxyapatite on titanium (Ti) has proven
      to be a suboptimal solution to improve orthopedic-implant success rates, as
      demonstrated by the increasing number of orthopedic revision surgeries due to
      infection, implant loosening, and a myriad of other reasons. This could be in
      part due to the high heat involved during plasma-spray deposition, which
      significantly increases hydroxyapatite crystal growth into the nonbiologically
      inspired micron regime. There has been a push to create nanotopographies on
      implant surfaces to mimic the physiological nanostructure of native bone and,
      thus, improve osteoblast (bone-forming cell) functions and inhibit bacteria
      functions. Among the several techniques that have been adopted to develop
      nanocoatings, electrophoretic deposition (EPD) is an attractive, versatile, and
      effective material-processing technique. OBJECTIVE: The in vitro study reported
      here aimed to determine for the first time bacteria responses to hydroxyapatite
      coated on Ti via EPD. RESULTS: There were six and three times more osteoblasts on
      the electrophoretic-deposited hydroxyapatite on Ti compared with Ti (control) and
      plasma-spray-deposited hydroxyapatite on Ti after 5 days of culture,
      respectively. Impressively, there were 2.9 and 31.7 times less Staphylococcus
      aureus on electrophoretic-deposited hydroxyapatite on Ti compared with Ti
      (control) and plasma-spray-deposited hydroxyapatite on Ti after 18 hours of
      culture, respectively. CONCLUSION: Compared with uncoated Ti and plasma-sprayed
      hydroxyapatite coated on Ti, the results provided significant promise for the use
      of EPD to improve bone-cell density and be used as an antibacterial coating
      without resorting to the use of antibiotics.

PMID- 24748790
TI  - A nanotechnological, molecular-modeling, and immunological approach to study the
      interaction of the anti-tumorigenic peptide p28 with the p53 family of proteins.
AB  - p28 is an anionic, amphipathic, cell-penetrating peptide derived from the
      cupredoxin azurin that binds to the DNA-binding domain (DBD) of the tumor
      suppressor protein, p53, and induces a post-translational increase in the level
      of wild type and mutated p53 in a wide variety of human cancer cells. As p63 and
      p73, additional members of the p53 superfamily of proteins, also appear to be
      involved in the cellular response to cancer therapy and are reportedly required
      for p53-induced apoptosis, we asked whether p28 also binds to p63 and p73. Atomic
      force spectroscopy demonstrates that p28 forms a stable, high-affinity complex
      with full-length p63, the DBD of p63, and full-length p73. Exposure to p28
      decreased the level of TAp63alpha and DeltaNp63alpha, the truncated form of p63,
      in p53 wild type and mutated human breast cancer cells, respectively. p28
      increased the level of TAp73alpha, but not DeltaNp73alpha, in the same breast
      cancer cell lines. In contrast, p28 increased the level of the TA and DeltaN
      isoforms of p63 in p53 wild type, but not in p53 mutated melanoma cells, while
      decreasing TA p73alpha in p53 wild type and mutated human melanoma cells. All
      changes were mirrored by an associated change in the expression of the HECT E3
      ligases Itch/AIP4, AIP5, and the RING E3 ligase Pirh2, but not in the receptor
      for activated C kinase or the RING E3 ligases Mdm2 and Cop1. Collectively, the
      data suggest that molecules such as p28 bind with high affinity to the DBD of p63
      and p73 and alter their expression independent of the Mdm2 and Cop1 pathways. 

PMID- 24748791
TI  - R2* and R2 mapping for quantifying recruitment of superparamagnetic iron oxide
      tagged endothelial progenitor cells to injured liver: tracking in vitro and in
      vivo.
AB  - OBJECTIVE: To evaluate clinical 3.0T magnetic resonance for tracking and
      quantifying superparamagnetic iron oxide (SPIO)-labeled endothelial progenitor
      cells (EPCs) in vitro and homing to liver with acute injury in vivo. METHODS: The
      bone marrow-derived EPCs were isolated and cultured for 4 days and examined in
      vitro for lineage markers. Then the cultured cells were labeled with a
      ferumoxides-protamine sulfate complex. Iron uptake was analyzed with an electron
      microscope and Prussian blue staining. Agarose gel phantoms containing different
      amounts of EPCs (0-2.5 * 10(6) cells per milliliter of 1.0% agarose gel) were
      analyzed with 3.0T R2 and R2* relaxometry. For in vivo tracking, liver injury was
      induced in healthy C57 mice (female, 6 weeks old, weight 19-20 g) by
      administration of carbon tetrachloride by single intraperitoneal injection. The
      R2* and R2 mapping of injured and normal livers of C57 mice were conducted by
      using 3.0T magnetic resonance on Days 0, 1, 4, and 8 after intravenous SPIO
      tagged cells transplantation. RESULTS: Electron microscope and Perls Prussian
      blue stain revealed the efficiency of SPIO particles uptake was more than 95% and
      no structural changes of labeled cells were found compared with control group. R2
      and R2* values were linearly correlated with the number of iron-loaded cells in
      the agarose gel phantoms, and R2* values were significantly greater than R2
      (P<0.01). R2* values in all groups were obviously greater than R2 (P<0.01). The
      R2* values of the injured livers were greater than normal on Days 1 and 4
      (P<0.01). No significant difference of R2 values could be found among the three
      groups. CONCLUSION: Quantitative R2* mapping provides a useful method for
      quantifying intravascular administered SPIO-tagged EPCs homing to injured livers.

PMID- 24748792
TI  - Development of a liposome-based formulation for vitamin K1 nebulization on the
      skin.
AB  - Vitamin K1 (VK1) is a very lipophilic and photosensitive molecule contained in
      some vegetables. Recently, the use of VK1 on the skin has been proposed for
      different pharmaceutical or cosmeceutical applications. In this study, an
      innovative strategy for the administration of VK1 on the skin was proposed. In
      particular, to overcome the drawbacks associated with a VK1-containing fatty
      ointment available on the market, an aqueous formulation suitable to be
      administered by nebulization was developed. The use of liposomes encapsulating
      VK1 enabled issues due to the lipophilicity of VK1 to be overcome. Thus,
      different liposomal formulations, with different VK1 concentrations, were
      prepared and characterized in terms of size, zeta potential, VK1 encapsulation
      into liposomes, and stability of the formulations during storage. After a first
      phase of screening, the selected formulation was tested by a portable device for
      nebulization. No alteration of the vesicle characteristics following the liposome
      supply through the nebulizer was found. Finally, permeation studies were carried
      out on pig-excised skin in Franz cells and the newly developed formulation was
      compared to a marketed VK1-containing ointment. In this test, an enhanced VK1
      accumulation into the skin was found when using nebulized liposomes. In
      conclusion, in order to administer VK1 on the skin, the newly developed
      formulation could be a valid alternative to the products available on the market
      today. In particular, the use of liposomes could facilitate the multiple
      administrations per day by aerosol, but also increase, compared to a semi-solid
      preparation, the accumulation of VK1 into the epidermis and dermis. 

PMID- 24748794
TI  - Exploratory study describing 6 month outcomes for young children with autism who
      receive treatment as usual in Italy.
AB  - BACKGROUND: In the last few years, the results of different studies have
      confirmed, in different ways, the importance of early intervention for autism.
      This study aims to evaluate the role of early "as usual" interventions in the
      outcome of toddlers diagnosed with autism spectrum disorder (ASD). METHOD:
      Seventy children with ASD aged between 24 and 48 months were recruited at
      different centers in Italy. They were evaluated by blind researchers at baseline
      and after 6 months of using Autism Diagnostic Observation Schedule-Generic (ADOS
      G), Griffiths Mental Developmental Scales, and Vineland Adaptive Behavior scales.
      Parents filled out the MacArthur Inventory, Social Communication Questionnaire,
      and Child Behavior Check List. All children were referred to community providers
      for available interventions. RESULTS: At the endpoint, most of the children were
      still classified as having an ADOS-G classification of ASD. However, 21 (34.2%)
      passed from autism to autism spectrum, and 3 (4.2%) passed from autism spectrum
      to no spectrum. Treatment effects were obtained for cognitive functioning,
      language, adaptive behavior, and child behavior without differences between
      development-oriented and behavior-oriented interventions. Parent involvement was
      a mediator for the best clinical outcome. Baseline low impairments of
      communication, language comprehension, and gesture were predictors of positive
      outcome. CONCLUSION: Treatment as usual, composed of individual therapy plus
      school-supported inclusion, may be an effective intervention in ASD. Better
      initial levels of communication in child and parent involvement during treatment
      have an important role for a positive outcome.

PMID- 24748793
TI  - Development of nucleic acid vaccines: use of self-amplifying RNA in lipid
      nanoparticles.
AB  - Self-amplifying RNA or RNA replicon is a form of nucleic acid-based vaccine
      derived from either positive-strand or negative-strand RNA viruses. The gene
      sequences encoding structural proteins in these RNA viruses are replaced by mRNA
      encoding antigens of interest as well as by RNA polymerase for replication and
      transcription. This kind of vaccine has been successfully assayed with many
      different antigens as vaccines candidates, and has been shown to be potent in
      several animal species, including mice, nonhuman primates, and humans. A key
      challenge to realizing the broad potential of self-amplifying vaccines is the
      need for safe and effective delivery methods. Ideally, an RNA nanocarrier should
      provide protection from blood nucleases and extended blood circulation, which
      ultimately would increase the possibility of reaching the target tissue. The
      delivery system must then be internalized by the target cell and, upon receptor
      mediated endocytosis, must be able to escape from the endosomal compartment into
      the cell cytoplasm, where the RNA machinery is located, while avoiding
      degradation by lysosomal enzymes. Further, delivery systems for systemic
      administration ought to be well tolerated upon administration. They should be
      safe, enabling the multiadministration treatment modalities required for improved
      clinical outcomes and, from a developmental point of view, production of large
      batches with reproducible specifications is also desirable. In this review, the
      concept of self-amplifying RNA vaccines and the most promising lipid-based
      delivery systems are discussed. 

PMID- 24748795
TI  - Sex differences in the prediction of the effectiveness of paroxetine for patients
      with major depressive disorder identified using a receiver operating
      characteristic curve analysis for early response.
AB  - BACKGROUND: We investigated cutoff values for the early response of patients with
      major depressive disorder to paroxetine and their sex differences by using a
      receiver operating characteristic (ROC) curve analysis to predict the
      effectiveness of paroxetine. METHODS: In total, 120 patients with major
      depressive disorder were enrolled and treated with 10-40 mg/day paroxetine for 6
      weeks; 89 patients completed the protocol. A clinical evaluation using the
      Montgomery-Asberg Depression Rating Scale (MADRS) was performed at weeks 0, 1, 2,
      4, and 6. RESULTS: In male subjects, the cutoff values for MADRS improvement
      rating in week 1, week 2, and week 4 were 20.9%, 34.9%, and 33.3%, respectively.
      The sensitivities and the specificities were 83.3% and 80.0%, 83.3% and 80.0%,
      and 100% and 90%, respectively. The areas under the curve (AUC) were 0.908,
      0.821, and 0.979, respectively. In female subjects, the cutoff values for the
      MADRS improvement rating in week 1, week 2, and week 4 were 21.4%, 35.7%, and
      32.3%, respectively. The sensitivities and the specificities were 71.4% and
      84.6%, 73.8% and 76.9%, and 90.5% and 76.9%, respectively. The AUCs were 0.781,
      0.735, and 0.904, respectively. CONCLUSION: Early improvement with paroxetine may
      predict the long-term response. The accuracy of the prediction for the response
      is higher in male subjects.

PMID- 24748796
TI  - Dopamine transporter changes after unilateral deep brain stimulation in
      progressive Parkinson's disease: a case report.
AB  - Deep brain stimulation (DBS) at the subthalamic nucleus has been approved as an
      effective treatment for refractory symptoms of Parkinson's disease (PD). Studies
      have shown that bilateral DBS surgery in PD patients results in clinical
      improvement without reducing dopamine transporter function. Here, we report our
      longitudinal findings in one PD patient, ie, decreases in striatal dopamine
      transporter binding during one year of follow-up after unilateral DBS at the
      subthalamic nucleus. Based on this case, we hypothesize that clinical benefit
      after unilateral DBS may be not directly associated with changes in function at
      the subthalamic nucleus. 

PMID- 24748797
TI  - Analysis of cardiac autonomic modulation of children with attention deficit
      hyperactivity disorder.
AB  - BACKGROUND: Attention deficit hyperactivity disorder (ADHD) is characterized by
      decreased attention span, impulsiveness, and hyperactivity. Autonomic nervous
      system imbalance was previously described in this population. We aim to compare
      the autonomic function of children with ADHD and controls by analyzing heart rate
      variability (HRV). METHODS: Children rested in supine position with spontaneous
      breathing for 20 minutes. Heart rate was recorded beat by beat. HRV analysis was
      performed in the time and frequency domains and Poincare plot. RESULTS: Twenty
      eight children with ADHD (22 boys, aged 9.964 years) and 28 controls (15 boys,
      age 9.857 years) participated in this study. It was determined that the mean and
      standard deviation of indexes which indicate parasympathetic activity is higher
      in children with ADHD than in children without the disorder: high frequency in
      normalized units, 46.182 (14.159) versus 40.632 (12.247); root mean square of
      successive differences, 41.821 (17.834) versus 38.150 (18.357); differences
      between adjacent normal-to-normal intervals greater than 50 milliseconds, 199.75
      (144.00) versus 127.46 (102.21) (P<0.05); percentage of differences between
      adjacent normal-to-normal intervals greater than 50 milliseconds, 23.957 (17.316)
      versus 16.211 (13.215); standard deviation of instantaneous beat-to-beat
      interval, 29.586 (12.622) versus 26.989 (12.983). CONCLUSION: Comparison of the
      autonomic function by analyzing HRV suggests an increase in the activity of the
      parasympathetic autonomic nervous systems in children with ADHD in relation to
      the control group.

PMID- 24748798
TI  - Successful percutaneous coronary intervention during cardiac arrest with use of
      an automated chest compression device: a case report.
AB  - Ventricular tachycardia or fibrillation (VT/VF) in patients with ST-elevation
      myocardial infarction (STEMI) is associated with poor prognosis. Performing
      manual chest compressions is a serious obstacle for treatment with percutaneous
      coronary intervention (PCI). Here we introduce a case with refractory VT/VF where
      the patient was successfully treated with an automated chest compression device,
      which made revascularization with PCI possible. 

PMID- 24748799
TI  - Stroke and diabetic ketoacidosis--some diagnostic and therapeutic considerations.
AB  - Cerebrovascular insult (CVI) is a known and important risk factor for the
      development of diabetic ketoacidosis (DKA); still, it seems that the prevalence
      of DKA among the patients suffering CVI and its influence on stroke outcome might
      be underestimated. Diabetic ketoacidosis itself has been reported to be a risk
      factor for the occurrence of stroke in children and youth. A cerebral
      hypoperfusion in untreated DKA may lead to cerebral injury, arterial ischemic
      stroke, cerebral venous thrombosis, and hemorrhagic stroke. All these were noted
      following DKA episodes in children. At least some of these mechanisms may be
      operative in adults and complicate the course and outcome of CVI. There is a
      considerable overlap of symptoms, signs, and laboratory findings in the two
      conditions, making their interpretation difficult, particularly in the elderly
      and less communicative patients. Serum pH and bicarbonate, blood gases, and anion
      gap levels should be routinely measured in all type 1 and type 2 diabetics,
      regardless of symptomatology, for the early detection of existing or pending
      ketoacidosis. The capacity for rehydration in patients with stroke is limited,
      and the treatment of the cerebrovascular disease requires intensive use of
      osmotic and loop diuretics. Fluid repletion may be difficult, and the precise
      management algorithms are required. Intravenous insulin is the backbone of
      treatment, although its effect may be diminished due to delayed fluid
      replenishment. Therefore, the clinical course of diabetic ketoacidosis in
      patients with CVI may be prolonged and complicated. 

PMID- 24748801
TI  - Telemonitoring: use in the management of hypertension.
AB  - Hypertension is a major modifiable risk factor for cardiovascular, retinal, and
      kidney disease. In the past decade, attainment rates of treatment targets for
      blood pressure control in the UK and US have increased; however, <11% of adult
      men and women have achieved adequate blood pressure control. Technological
      advances in blood pressure measurement and data transmission may improve the
      capture of information but also alter the relationship between the patient and
      the provider of care. Telemonitoring systems can be used to manage patients with
      hypertension, and have the ability to enable best-practice decisions more
      consistently. The improvement in choice for patients as to where and who manages
      their hypertension, as well as better adherence to treatment, are potential
      benefits. An evidence base is growing that shows that telemonitoring can be more
      effective than usual care in improving attainment rates of goal blood pressure in
      the short-to-medium term. In addition, studies are in progress to assess whether
      this technology could be a part of the solution to address the health care needs
      of an aging population and improve access for those suffering health
      inequalities. The variation in methods and systems used in these studies make
      generalizability to the general hypertension population difficult. Concerns over
      the reliability of technology, impact on patient quality of life, longer-term
      utility and cost-benefit analyses all need to be investigated further if wider
      adoption is to occur. 

PMID- 24748800
TI  - Current guidelines for high-density lipoprotein cholesterol in therapy and future
      directions.
AB  - Many studies have suggested that a significant risk factor for atherosclerotic
      cardiovascular disease (ASCVD) is low high-density lipoprotein cholesterol (HDL
      C). Therefore, increasing HDL-C with therapeutic agents has been considered an
      attractive strategy. In the prestatin era, fibrates and niacin monotherapy, which
      cause modest increases in HDL-C, reduced ASCVD events. Since their introduction,
      statins have become the cornerstone of lipoprotein therapy, the benefits of which
      are primarily attributed to decrease in low-density lipoprotein cholesterol.
      Findings from several randomized trials involving niacin or cholesteryl ester
      transfer protein inhibitors have challenged the concept that a quantitative
      elevation of plasma HDL-C will uniformly translate into ASCVD benefits.
      Consequently, the HDL, or more correctly, HDL-C hypothesis has become more
      controversial. There are no clear guidelines thus far for targeting HDL-C or HDL
      due to lack of solid outcomes data for HDL specific therapies. HDL-C levels are
      only one marker of HDL out of its several structural or functional properties.
      Novel approaches are ongoing in developing and assessing agents that closely
      mimic the structure of natural HDL or replicate its various functions, for
      example, reverse cholesterol transport, vasodilation, anti-inflammation, or
      inhibition of platelet aggregation. Potential new approaches like HDL infusions,
      delipidated HDL, liver X receptor agonists, Apo A-I upregulators, Apo A mimetics,
      and gene therapy are in early phase trials. This review will outline current
      therapies and describe future directions for HDL therapeutics. 

PMID- 24748802
TI  - An assessment of the quality of advice provided by patent medicine vendors to
      users of oral contraceptive pills in urban Nigeria.
AB  - INTRODUCTION: In Nigeria about 50% of oral contraceptive pill users obtain their
      products from proprietary patent medicine vendors (PPMVs). This group of service
      providers are poorly trained and have very limited knowledge about contraception.
      This paper investigated the nature of the advice offered to simulated current and
      potential users of oral contraceptive pills. The main objective was to assess the
      nature and quality of advice provided by PPMVs to pill users. METHOD: This study
      is based on findings from a 'mystery client' approach in which three scenarios
      related to contraceptive pill use were simulated. Each of the 12 mystery clients
      simulated one of the following three scenarios: new pill users (new to family
      planning or switching from condom to pills); user seeking a resupply of pills;
      and dissatisfied pill users intending to discontinue use. Simple random sampling
      was used to select 410 PPMVs from a total of 1,826 in four states in Nigeria.
      Qualitative study using in-depth interviews was also conducted. RESULTS: A
      majority of the PPMVs had pills in stock on the day of the survey and resupplied
      pills to the clients. PPMVs also understood the reason and importance of
      referring clients who were new adopters of oral contraceptive methods to a health
      facility; 30% of the PPMVs referred new adopters to a health facility. However,
      demand from clients who do not want to go to health care facilities (for various
      reasons) necessitated the provision of oral contraceptive pills to 41% of the
      first time users. Some PPMVs prescribed treatment to mystery clients who
      presented with perceived complications arising from the use of pills, while 49%
      were referred to a health facility. CONCLUSION: The advice given by PPMVs often
      falls short of safety guidelines related to the use of oral contraceptive pills.
      There is a need to continuously update knowledge among the PPMVs to ensure that
      they provide quality oral contraceptive services as PPMVs bridge the gap between
      medical experts and users in rural communities.

PMID- 24748803
TI  - Characterization of a fusion protein of RGD4C and the beta-lactamase variant for
      antibody-directed enzyme prodrug therapy.
AB  - Antibody-directed enzyme prodrug therapy (ADEPT) delivers chemotherapeutic agents
      in high concentration to tumor tissue, while minimizing systemic drug exposure.
      ADEPT has been reported to be an attractive approach for improving the efficacy
      of cancer therapy. A previously reported beta-lactamase was found to contain four
      cluster of differentiation (CD)4(+) T cell epitopes; however, single amino acid
      changes in the enzyme resulted in significantly reduced proliferative responses,
      while retaining stability and activity of the enzyme. The beta-lactamase variant
      with reduced immunogenicity is an attractive alternative for constructing the
      ADEPT fusion protein. In this study, we fused the peptide, RGD4C, known to target
      integrin alphavbeta3, to the beta-lactamase variant for use in ADEPT. Biological
      function studies revealed that RGD4C-beta-lactamase had a high hydrolytic effect
      on nitrocefin and cephalosporin-melphalan, and high plasma stability was
      observed. In addition, fusion of the RGD4C moiety to beta-lactamase had little
      effect on immunogenicity compared with beta-lactamase in the proliferation of
      peripheral blood mononuclear cells. The ability of this fusion protein to both
      target the central region of alphavbeta3 and induce toxicity in the non-small
      cell lung cancer cell NCI-H460 makes it a promising therapeutic approach in the
      treatment of cancer. 

PMID- 24748804
TI  - PIK3CA mutations define favorable prognostic biomarkers in operable breast
      cancer: a systematic review and meta-analysis.
AB  - BACKGROUND: Mutations of the p110alpha catalytic subunit of phosphatidylinositol
      3-kinase (PIK3CA) are among the most common genetic aberrations in human breast
      cancer. At present, controversy exists concerning the prognostic value of the
      mutations. METHODS: We performed a systematic review and meta-analysis to clarify
      the association between PIK3CA mutations and survival outcomes. A comprehensive,
      computerized literature search of PubMed, Web of Science databases, the Chinese
      Biomedical Literature Database, and Wangfang Data until August 27, 2013 was
      carried out. Eligible studies were included according to specific inclusion
      criteria. Pooled hazard ratio was estimated by using the fixed effects model or
      random effects model according to heterogeneity between studies. RESULTS: Eight
      eligible studies were included in the analysis, all of which were retrospective
      cohort studies. The overall meta-analysis demonstrated that the PIK3CA mutations
      were associated with better clinical outcomes (hazard ratio 0.72; 95% confidence
      interval: 0.57-0.91; P=0.006). None of the single studies materially altered the
      original results and no evidence of publication bias was found. Further subgroup
      analysis of mutations in exons 9 and 20 did not show statistical significance.
      CONCLUSION: PIK3CA mutations in operable primary breast cancer indicate a good
      prognosis. Further studies should be conducted to investigate the effect of
      PIK3CA mutations on clinical outcomes in different histologic types, different
      molecular subtypes of breast cancer, and different exons of PIK3CA.

PMID- 24748805
TI  - Hypofractionated helical tomotherapy (75 Gy at 2.5 Gy per fraction) for localized
      prostate cancer: long-term analysis of gastrointestinal and genitourinary
      toxicity.
AB  - BACKGROUND: This study is a report on the long-term analysis of acute and late
      toxicities for patients with localized prostate cancer treated with
      hypofractionated helical tomotherapy. METHODS: From January 2008 through August
      2013, 70 patients with localized prostate cancer were treated definitively with
      hypofractionated helical tomotherapy. The helical tomotherapy was designed to
      deliver 75 Gy in 2.5 Gy per fraction to the prostate gland, 63 Gy in 2.1 Gy per
      fraction to the seminal vesicles, and 54 Gy in 1.8 Gy per fraction to the pelvic
      lymph nodes. Incidence rates and predictive factors for radiation toxicities were
      analyzed retrospectively. RESULTS: The incidences of grades 0, 1, and 2 acute
      gastrointestinal (GI) toxicity were 51.4%, 42.9%, and 5.7%, and those of acute
      genitourinary (GU) toxicity were 7.1%, 64.3%, and 28.6%, respectively. The
      maximum dose of rectum and bladder V40 and V50 were significant predictive
      factors for acute GI and GU toxicity. The cutoff value of rectum maximum dose and
      bladder V40 and V50 by receiver-operating characteristic curves analysis were
      76.5 Gy, 17.3%, and 10.2%, respectively. The incidences of grades 0, 1, and 2
      late GI toxicity were 82.0%, 14.0%, and 4.0%, and those of late GU toxicity were
      18.0%, 56.0%, and 26.0%, respectively. Rectum V70 and bladder V70 and V75 were
      significant predictive factors for late GI and GU toxicity. The cutoff value of
      rectum V70 and bladder V70 and V75 by receiver-operating characteristic curves
      analysis was 2.8%, 2.8%, and 1.0%, respectively. CONCLUSION: Hypofractionated
      helical tomotherapy using a schedule of 75 Gy at 2.5 Gy per fraction had
      favorable acute and late toxicity rates and no serious complication, such as
      grade 3 or worse toxicity. To minimize radiation toxicities, constraining the
      rectum maximum dose to less than 76.5 Gy, rectum V70 to less than 2.8%, bladder
      V40 to less than 17.3%, bladder V50 to less than 10.2%, bladder V70 to less than
      2.8%, and bladder V75 to less than 1.0% would be necessary.

PMID- 24748806
TI  - Protein expression of programmed death 1 ligand 1 and ligand 2 independently
      predict poor prognosis in surgically resected lung adenocarcinoma.
AB  - BACKGROUND: The clinicopathologic characteristics of tumors expressing programmed
      death (PD-1) ligands (PD-Ls) PD-L1 or PD-L2 and their associations with common
      driver mutations in lung adenocarcinoma are not clearly defined, despite the
      progression of anti-PD-1/PD-L1 immunotherapy. METHODS: PD-L1 and PD-L2 expression
      was measured by immunohistochemistry in 143 surgically resected lung
      adenocarcinomas and was correlated with clinical variables, histologic subtypes,
      and the mutational status of EGFR, KRAS, HER2, and ALK. RESULTS: Positive PD-L1
      expression was significantly associated with more advanced T status, N status,
      and pathologic stage. Histologically, lung adenocarcinomas with positive PD-L1
      staining were less likely to be adenocarcinoma in situ or minimally invasive
      adenocarcinoma and more likely to have solid predominant subtype. Both PD-L1
      expression (odds ratio =1.984, 95% confidence interval =1.010-3.894; P=0.047) and
      PD-L2 expression (odds ratio =2.328, 95% confidence interval =1.201-4.512;
      P=0.012) were independent predictors of poor overall survival. When the combined
      PD-L expression and pathologic stage were used together to predict overall
      survival, the concordance index increased to 0.763, and the Akaike information
      criteria value decreased to 356.08. CONCLUSION: We defined the clinicopathologic
      features of lung adenocarcinomas with high expression of PD-L1 and PD-L2. We
      further demonstrated the role of PD-L expression as a useful prognostic marker
      for lung adenocarcinoma.

PMID- 24748807
TI  - Switching patients from other inhaled corticosteroid devices to the
      Easyhaler((r)): historical, matched-cohort study of real-life asthma patients.
AB  - PURPOSE: To investigate the clinical and cost effectiveness of switching real
      life asthma patients from other types of inhalers to the Easyhaler((r)) (EH) for
      the administration of inhaled corticosteroids (ICS). PATIENTS AND METHODS:
      Historical, matched-cohort study of 1,958 asthma patients (children and adults)
      treated in UK primary-care practices, using data obtained from the Optimum
      Patient Care Research Database and Clinical Practice Research Datalink. Other
      inhalers (OH) included pressurized metered-dose inhalers, breath-actuated
      inhalers, and dry-powder inhalers, delivering beclomethasone, budesonide,
      fluticasone, or ciclesonide. Patients remaining on OH unchanged (same drug,
      dosage, and device; n=979) were matched 1:1 with those switched to the EH
      (beclomethasone or budesonide) at the same or lower ICS dosage (n=979), based on
      age, sex, year of index patient review/switch, most recent ICS drug, dosage, and
      device, and the number of severe exacerbations and average daily short-acting
      beta2 agonist (SABA) dosage in the preceding year. Clinical outcomes and health
      care costs were compared between groups for 12 months before and after the
      switch. Co-primary clinical outcomes were: 1) risk domain asthma control (RDAC) -
      no asthma-related hospitalization, acute oral steroid use, or lower respiratory
      tract infection (LRTI); 2) exacerbation rate (American Thoracic Society [ATS]
      definition) - where exacerbation is asthma-related hospitalization or acute oral
      steroid use; 3) exacerbation rate (clinical definition) - where exacerbation is
      ATS exacerbation or LRTI; and 4) overall asthma control (OAC) - RDAC plus average
      salbutamol-equivalent SABA dosage <=200 MUg/day. Non-inferiority (at least
      equivalence) of EH was tested against OH for the four co-primary outcomes in
      order (hierarchical approach) by comparing the difference in proportions of
      patients [EH-OH] achieving asthma control or having no exacerbations in the
      outcome year, using a limit of 10% difference. RESULTS: Non-inferiority was shown
      for the EH for all four co-primary outcomes. There were no significant
      differences between groups for RDAC or exacerbation rates, but EH patients were
      significantly more likely to achieve OAC (adjusted odds ratio [95% confidence
      interval]: 1.26 [1.05, 1.52]), as significantly more EH than OH patients had an
      average SABA dosage of <=200 MUg/day (52% versus 47%, respectively; P<0.001).
      Mean asthma-related health care costs increased from baseline to outcome years in
      both groups, but SABA costs increased significantly more in OH than EH patients
      (mean difference L5.5/patient/year) and consultation costs decreased
      significantly more in EH than OH patients (mean difference L13.5/patient/year).
      CONCLUSION: Typical asthma patients may be switched from other ICS devices to the
      Easyhaler((r)) with no reduction in clinical effectiveness or increase in cost.

PMID- 24748809
TI  - Group-based trajectory modeling to assess adherence to biologics among patients
      with psoriasis.
AB  - BACKGROUND: Proportion of days covered (PDC), a commonly used adherence metric,
      does not provide information about the longitudinal course of adherence to
      treatment over time. Group-based trajectory model (GBTM) is an alternative method
      that overcomes this limitation. METHODS: The statistical principles of GBTM and
      PDC were applied to assess adherence during a 12-month follow-up in psoriasis
      patients starting treatment with a biologic. The optimal GBTM model was
      determined on the basis of the balance between each model's Bayesian information
      criterion and the percentage of patients in the smallest group in each model.
      Variables potentially predictive of adherence were evaluated. RESULTS: In all,
      3,249 patients were included in the analysis. Four GBTM adherence groups were
      suggested by the optimal model, and patients were categorized as demonstrating
      continuously high adherence, high-then-low adherence, moderate-then-low
      adherence, or consistently moderate adherence during follow-up. For comparison,
      four PDC groups were constructed: PDC Group 4 (PDC >=75%), PDC Group 3 (25%<= PDC
      <50%), PDC Group 2 (PDC <25%), and PDC Group 1 (50%<= PDC <75%). Our findings
      suggest that the majority of patients (97.9%) from PDC Group 2 demonstrated
      moderate-then-low adherence, whereas 96.4% of patients from PDC Group 4 showed
      continuously high adherence. The remaining PDC-based categorizations did not
      capture patients with uniform adherence behavior based on GBTM. In PDC Group 3,
      25.3%, 17.2%, and 57.5% of patients exhibited GBTM-defined consistently moderate
      adherence, moderate-then-low adherence, or high-then-low adherence, respectively.
      In PDC Group 1, 70.8%, 23.6%, and 5.7% of patients had consistently moderate
      adherence, high-then-low adherence, and continuously high adherence,
      respectively. Additional analyses suggested GBTM-based categorization was best
      predicted by patient age, sex, certain comorbidities, and particular drug use.
      CONCLUSION: GBTM is a more appropriate way to model dynamic behaviors and offers
      researchers an alternative to more traditional drug adherence measurements.

PMID- 24748808
TI  - Diagnosis and management of eosinophilic asthma: a US perspective.
AB  - Eosinophilic asthma is now recognized as an important subphenotype of asthma
      based on the pattern of inflammatory cellular infiltrate in the airway.
      Eosinophilic asthma can be associated with increased asthma severity, atopy, late
      onset disease, and steroid refractoriness. Induced sputum cell count is the gold
      standard for identifying eosinophilic inflammation in asthma although several
      noninvasive biomarkers, including fractional exhaled nitric oxide and periostin,
      are emerging as potential surrogates. As novel therapies and biologic agents
      become increasingly available, there is an increased need for specific phenotype
      directed treatment strategies. Greater recognition and understanding of the
      unique immunopathology of this asthma phenotype has important implications for
      management of the disease and the potential to improve patient outcomes. The
      present review provides a summary of the clinical features, pathogenesis,
      diagnosis, and management of eosinophilic asthma. 

PMID- 24748810
TI  - Asymmetric facial skin viscoelasticity during climacteric aging.
AB  - BACKGROUND: Climacteric skin aging affects certain biophysical characteristics of
      facial skin. The purpose of the present study was to assess the symmetric
      involvement of the cheeks in this stage of the aging process. METHODS: Skin
      viscoelasticity was compared on both cheeks in premenopausal and post-menopausal
      women with indoor occupational activities somewhat limiting the influence of
      chronic sun exposure. Eighty-four healthy women comprising 36 premenopausal women
      and 48 early post-menopausal women off hormone replacement therapy were enrolled
      in two groups. The tensile characteristics of both cheeks were tested and
      compared in each group. A computerized suction device equipped with a 2 mm
      diameter hollow probe was used to derive viscoelasticity parameters during a five
      cycle procedure of 2 seconds each. Skin unfolding, intrinsic distensibility,
      biological elasticity, and creep extension were measured. RESULTS: Both
      biological elasticity and creep extension were asymmetric on the cheeks of the
      post-menopausal women. In contrast, these differences were more discrete in the
      premenopausal women. CONCLUSION: Facial skin viscoelasticity appeared to be
      asymmetric following menopause. The possibility of asymmetry should be taken into
      account in future studies of the effects of hormone replacement therapy and any
      antiaging procedure on the face in menopausal women.

PMID- 24748811
TI  - Management of Crohn's disease in poor responders to adalimumab.
AB  - Anti-tumor necrosis factor therapy with adalimumab is an effective therapy for
      the induction and maintenance of remission in moderate to severe Crohn's disease.
      Although a large proportion of patients show a favorable clinical response to
      adalimumab, therapy failure is common. In this review, we provide a practical
      overview of adalimumab therapy in patients with Crohn's disease, with a specific
      focus on the clinical management of adalimumab failure. In the case of inadequate
      efficacy, a thorough assessment is required to confirm inflammatory disease
      activity and rule out noninflammatory causes. Evaluation may include biomarkers
      (fecal calprotectin and serum C-reactive protein), colonoscopy, and/or magnetic
      resonance enterography/enteroclysis. Furthermore, adalimumab trough levels and
      antibodies to adalimumab are informational after the confirmation of active
      inflammation. In the case of low or undetectable adalimumab trough levels, dose
      escalation to 40 mg weekly is recommended, whereas high antibody titers or
      adverse events frequently require switching to an alternative anti-TNF agent such
      as infliximab. Active inflammation despite therapeutic adalimumab trough levels
      requires alternative strategies such as switching to drugs with a different mode
      of action or surgical intervention. 

PMID- 24748812
TI  - A randomized, double-blind, placebo-controlled, dose-ranging study using Genz
      644470 and sevelamer carbonate in hyperphosphatemic chronic kidney disease
      patients on hemodialysis.
AB  - BACKGROUND: Genz-644470 is a new, nonabsorbed phosphate binding polymer. In an in
      vitro competitive phosphate binding assay, Genz-644470 bound significantly more
      phosphate per gram than sevelamer. As a consequence, this clinical study
      evaluated the ability of Genz-644470 to lower serum phosphorus in patients on
      hemodialysis and compared serum phosphorus lowering of Genz-644470 with sevelamer
      carbonate and placebo. Because three different fixed doses of Genz-644470 and
      sevelamer carbonate were used, phosphate-lowering dose-responses of each agent
      were also analyzed. METHODS: A randomized, double-blind, dose-ranging study was
      conducted. After a 2-week phosphate binder washout, 349 hyperphosphatemic (serum
      phosphorus >5.5 mg/dL) hemodialysis patients were randomized to one of seven
      fixed-dose groups: placebo, Genz-644470 2.4 g/day, Genz-644470 4.8 g/day, Genz
      644470 7.2 g/day, sevelamer carbonate 2.4 g/day, sevelamer carbonate 4.8 g/day,
      or sevelamer carbonate 7.2 g/day. Indicated total daily doses were administered
      in fixed divided doses three times a day with meals for 3 weeks. The change in
      serum phosphorus during the treatment period and its dose-response patterns were
      assessed. RESULTS: Dose-dependent reductions in serum phosphorus were observed
      with both Genz-644470 and sevelamer carbonate. Serum phosphorus-lowering
      responses to fixed doses of sevelamer carbonate and Genz-644470 were enhanced in
      a roughly linear fashion with increasing doses over a threefold range after 3
      weeks of treatment. Genz-644470 did not show any advantage in phosphorus lowering
      per gram of binder compared with sevelamer carbonate. Overall toler-ability was
      similar between active treatment groups. The tolerability of sevelamer carbonate
      was consistent with prior studies and with the established safety profile of
      sevelamer. CONCLUSION: Both Genz-644470 and sevelamer carbonate effectively
      lowered serum phosphate levels in a dose-dependent fashion in patients with
      chronic kidney disease on hemodialysis. However, Genz-644470 did not provide any
      advantage over sevelamer carbonate in phosphate lowering in vivo, as had been
      demonstrated in vitro.

PMID- 24748814
TI  - Tackling chronic migraine: current perspectives.
AB  - In the last decade, several diagnostic criteria and definitions have been
      proposed for chronic migraine (CM). The third edition of the International
      Classification of Headache Disorders-3 beta, published in 2013, has revised CM
      diagnostic criteria. CM is defined as "headache occurring on 15 or more days per
      month for more than 3 months, which has the features of migraine headache on at
      least 8 days per month." Patients who meet the criteria for CM and for medication
      overuse headache should be given both diagnoses. Worldwide, CM prevalence ranges
      1%-3%, and its incidence has been estimated to be 2.5% per year. CM is associated
      with disability and poor quality of life. Modifiable risk factors include (among
      others): migraine progression (defined as an increase in frequency and severity
      of migraine attacks); medication and caffeine overuse; obesity; stressful life
      events; and snoring. CM patients have a significantly higher frequency of some
      comorbid conditions, including chronic pain, psychiatric disorders, respiratory
      illness, and some vascular risk factors. Management includes identification and
      control of comorbidities and risk factors that predispose to CM; treatment and
      prevention for medication overuse; early treatment for migraine attacks; and an
      adequate preventive therapy for CM. Several randomized controlled clinical trials
      have shown the efficacy of topiramate, amitriptyline, onabotulinumtoxinA, and
      cognitive-behavioral therapy in CM. 

PMID- 24748813
TI  - A review of the epidemiological and clinical aspects of West Nile virus.
AB  - The resurgence of West Nile virus (WNV) in North America and Europe in recent
      years has raised the concerns of local authorities and highlighted that mosquito
      borne disease is not restricted to tropical regions of the world. WNV is
      maintained in enzootic cycles involving, primarily, Culex spp. mosquitoes and
      avian hosts, with epizootic spread to mammals, including horses and humans. Human
      infection results in symptomatic illness in approximately one-fifth of cases and
      neuroinvasive disease in less than 1% of infected persons. The most consistently
      recognized risk factor for neuroinvasive disease is older age, although diabetes
      mellitus, alcohol excess, and a history of cancer may also increase risk. Despite
      the increasing public health concern, the current WNV treatments are inadequate.
      Current evidence supporting the use of ribavirin, interferon alpha, and WNV
      specific immunoglobulin are reviewed. Nucleic acid detection has been an
      important diagnostic development, which is particularly important for the
      protection of the donated blood supply. While effective WNV vaccines are widely
      available for horses, no human vaccine has been registered. Uncertainty surrounds
      the magnitude of future risk posed by WNV, and predictive models are limited by
      the heterogeneity of environmental, vector, and host factors, even in neighboring
      regions. However, recent history has demonstrated that for regions where suitable
      mosquito vectors and reservoir hosts are present, there will be a risk of major
      epidemics. Given the potential for these outbreaks to include severe
      neuroinvasive disease, strategies should be implemented to monitor for, and
      respond to, outbreak risk. While broadscale mosquito control programs will assist
      in reducing the abundance of mosquito populations and subsequently reduce the
      risks of disease, for many individuals, the use of topical insect repellents and
      other personal protective strategies will remain the first line of defense
      against infection. 

PMID- 24748815
TI  - Incidence of neuropathic pain after radiofrequency denervation of the third
      occipital nerve.
AB  - The purpose of this study was to identify the incidence of neuropathic pain
      occurring after radiofrequency neurotomy of the third occipital nerve (TON). This
      study was conducted at a teaching hospital from January 1, 2008, to March 31,
      2010. With institutional review board approval, Current Procedural Terminology
      codes were used to identify patients who received radiofrequency ablation (RFA)
      of the nerves supplying the C2-3 facet joint and the TON. The C3 dorsal ramus
      provides innervation to the C2-3 facet joint and the suboccipital cutaneous
      region, and procedures that included ablation to this region were reviewed for
      complications. Postprocedural data were collected by reviewing follow-up
      appointment notes and telephone calls. Included were patients who had new
      neuropathic pain in the distribution of the TON after RFA. They described what
      they were feeling as burning, tingling, or numbness. All patients who presented
      with complaints had normal neurologic findings and no secondary cause for their
      symptoms. The included patient medical records were then reviewed for severity
      and duration of symptoms and the need for treatment with pain medication. Sixty
      four patients underwent C2-3 RFA or TON RFA, and 12 patients were identified as
      experiencing ablation-induced third occipital neuralgia, an incidence rate of
      19%. This finding suggests that patients undergoing RFA of the nerves supplying
      the C2-3 joint or TON are at risk for postprocedural third occipital neuralgia.
      This possibility may affect providing informed consent as well as anticipating
      and managing postprocedural pain. 

PMID- 24748817
TI  - Clinical trial data in support of changing guidelines in osteoarthritis
      treatment.
AB  - Goals for the management of osteoarthritis (OA) emphasize pain relief, reduction
      of inflammation, and improvement in functioning. Among pharmacological pain
      management interventions, nonsteroidal anti-inflammatory drugs (NSAIDs) are
      frequently recommended as the most effective treatment option for OA. However,
      the use of traditional oral NSAIDs is associated with risk of serious adverse
      events involving the gastrointestinal, cardiovascular, and renal systems. Topical
      NSAIDs are an alternative with well-established tolerability and efficacy in the
      treatment of OA of the knee or hand. While the management of OA pain is evolving
      toward the more widespread use of topical NSAIDs, some OA management guidelines
      have yet to incorporate these agents in their recommendations. This review
      examines the efficacy and tolerability of topical NSAIDs, their current placement
      in OA management guidelines, and their potential role in enabling pain
      specialists to provide individualized care for their patients with OA. 

PMID- 24748816
TI  - No evidence of real progress in treatment of acute pain, 1993-2012: scientometric
      analysis.
AB  - Over the past 2 decades, many new techniques and drugs for the treatment of acute
      pain have achieved widespread use. The main aim of this study was to assess the
      progress in their implementation using scientometric analysis. The following
      scientometric indices were used: 1) popularity index, representing the share of
      articles on a specific technique (or a drug) relative to all articles in the
      field of acute pain; 2) index of change, representing the degree of growth in
      publications on a topic compared to the previous period; and 3) index of
      expectations, representing the ratio of the number of articles on a topic in the
      top 20 journals relative to the number of articles in all (>5,000) biomedical
      journals covered by PubMed. Publications on specific topics (ten techniques and
      21 drugs) were assessed during four time periods (1993-1997, 1998-2002, 2003
      2007, and 2008-2012). In addition, to determine whether the status of routine
      acute pain management has improved over the past 20 years, we analyzed surveys
      designed to be representative of the national population that reflected direct
      responses of patients reporting pain scores. By the 2008-2012 period, popularity
      index had reached a substantial level (>=5%) only with techniques or drugs that
      were introduced 30-50 years ago or more (epidural analgesia, patient-controlled
      analgesia, nerve blocks, epidural analgesia for labor or delivery, bupivacaine,
      and acetaminophen). In 2008-2012, promising (although modest) changes of index of
      change and index of expectations were found only with dexamethasone. Six national
      surveys conducted for the past 20 years demonstrated an unacceptably high
      percentage of patients experiencing moderate or severe pain with not even a trend
      toward outcome improvement. Thus, techniques or drugs that were introduced and
      achieved widespread use for acute pain management within the past 20 years have
      produced no changes in scientometric indices that would indicate real progress
      and have failed to improve national outcomes for relief of acute pain. Two
      possible reasons for this are discussed: 1) the difference between the
      effectiveness of old and new techniques is not clinically meaningful; and 2)
      resources necessary for appropriate use of new techniques in routine pain
      management are not adequate. 

PMID- 24748818
TI  - Existing data sources for clinical epidemiology: Aarhus University Clinical Trial
      Candidate Database, Denmark.
AB  - Denmark is facing a reduction in clinical trial activity as the pharmaceutical
      industry has moved trials to low-cost emerging economies. Competitiveness in
      industry-sponsored clinical research depends on speed, quality, and cost. Because
      Denmark is widely recognized as a region that generates high quality data, an
      enhanced ability to attract future trials could be achieved if speed can be
      improved by taking advantage of the comprehensive national and regional
      registries. A "single point-of-entry" system has been established to support
      collaboration between hospitals and industry. When assisting industry in early
      stage feasibility assessments, potential trial participants are identified by use
      of registries to shorten the clinical trial startup times. The Aarhus University
      Clinical Trial Candidate Database consists of encrypted data from the Danish
      National Registry of Patients allowing an immediate estimation of the number of
      patients with a specific discharge diagnosis in each hospital department or
      outpatient specialist clinic in the Central Denmark Region. The free access to
      health care, thorough monitoring of patients who are in contact with the health
      service, completeness of registration at the hospital level, and ability to link
      all databases are competitive advantages in an increasingly complex clinical
      trial environment. 

PMID- 24748819
TI  - Incidence of and risk factors for febrile morbidity after laparoscopic-assisted
      vaginal hysterectomy.
AB  - BACKGROUND: The purpose of this study was to assess the incidence of and risk
      factors for postoperative febrile morbidity after laparoscopic-assisted vaginal
      hysterectomy (LAVH). METHODS: This retrospective study was carried out using the
      medical records of women with benign gynecologic conditions who underwent LAVH
      between June 2007 and May 2012 at Srinagarind Hospital in Thailand. Data were
      collected to assess baseline patient characteristics, occurrence of body
      temperature >=38 degrees C on two occasions at least 6 hours apart in the 24
      hours following the surgical procedure, and possible risk factors related to
      postoperative febrile morbidity. RESULTS: In total, 199 women underwent LAVH
      during the study period. They had a mean age of 46+/-6 years, a mean body mass
      index of 24.0+/-3.2 kg/m(2), a mean surgical duration of 134+/-52 minutes, median
      estimated blood loss of 200 mL, a mean total hospital stay of 5+/-2 days, and a
      mean postoperative hospital stay of 3+/-2 days. Postoperative febrile morbidity
      was documented in 31 cases (15.6%). The cause of postoperative fever was unknown
      in most cases, with only two cases having an identifiable cause. The risk of
      postoperative febrile morbidity was highest in women treated with more than two
      antibacterial agents and with a regimen of more than 3 days. CONCLUSION: This
      study shows a moderately high rate of febrile morbidity after LAVH, for which the
      main risk factors were use of multiple drugs and doses for antibiotic
      prophylaxis.

PMID- 24748820
TI  - Stakeholder perceptions of misoprostol: a qualitative investigation.
AB  - The study aimed to explore perceptions of stakeholders regarding misoprostol use
      in Cambodia, a setting with high maternal mortality. Semi-structured expert
      interviews were conducted with 21 participants in the capital, Phnom Penh. The
      sample included participants involved in providing reproductive health services
      through international and local health agencies and the pharmaceutical industry.
      A theme of controversy over the role of misoprostol in the context of
      reproductive health services emerged, along with a need to reconcile legitimate
      viewpoints in order to understand the place of misoprostol in the Cambodian
      reproductive health setting. Understanding stakeholder perspectives on
      misoprostol can shed light on the drug's role in reproductive health programming
      where maternal mortality is high and health facilities are still improving. 

PMID- 24748821
TI  - Determinants of postpartum anemia among women from a rural population in southern
      India.
AB  - BACKGROUND: Even though the problem of anemia during pregnancy has been
      adequately emphasized, very little attention has been paid to postpartum anemia.
      The objective of the current study was to estimate the mean change in maternal
      hemoglobin from 36 weeks' gestation to 6 weeks postpartum and to identify the
      factors associated with anemia during the postpartum period among women in a
      rural development block in Tamil Nadu, India. METHODS: Ninety-three pregnant
      women were interviewed using a structured questionnaire at 36 weeks' gestation
      and then at 2 and 6 weeks postpartum. Blood samples were collected from the
      participants at 36 weeks' gestation and at 6 weeks postpartum. Paired t-tests
      assessing the difference in mean hemoglobin prepartum and postpartum, univariate
      analysis, and multiple logistic regression to identify factors associated with
      postpartum anemia were done using Statistical Package for the Social Sciences
      version 12 for Microsoft Windows software. RESULTS: The proportion of study
      subjects who were anemic (hemoglobin <11 g/dL) at 36 weeks' gestation was 26.8%
      and at 6 weeks postpartum was 47.3% (hemoglobin <12 g/dL). The mean hemoglobin at
      36-38 weeks' gestation was 11.70+/-1.43 g/dL and at 6 weeks postpartum was
      12.10+/-1.27 g/dL. Anemia at 36 weeks' gestation (odds ratio [OR] 10.47, 95%
      confidence interval [CI] 2.37-42.34), heavy blood loss perceived by the mother
      during delivery (OR 12.91, 95% CI 2.01-61.25), younger maternal age (<21 years,
      OR 2.45, 95% CI 1.28-23.86), and inadequate iron supplementation during the
      postpartum period (OR 3.53, 95% CI 1.18-11.37) were identified as significant
      factors associated with anemia at 6 weeks postpartum. CONCLUSION: Anemia during
      the third trimester of pregnancy, heavy bleeding perceived by the mother during
      delivery, younger maternal age, and inadequate iron supplementation during the
      postpartum period were associated with postpartum anemia.

PMID- 24748822
TI  - Doxylamine succinate-pyridoxine hydrochloride (Diclegis) for the management of
      nausea and vomiting in pregnancy: an overview.
AB  - Nausea and vomiting in pregnancy (NVP) is common and often undertreated, in part
      due to fears of adverse effects of medications on the fetus during early
      pregnancy. In April 2013, the US Food and Drug Administration (FDA) approved
      doxylamine succinate 10 mg and pyridoxine hydrochloride (a vitamin B6 analog) 10
      mg as a delayed-release combination pill called Diclegis for the treatment of
      NVP. Diclegis is currently the only medication that is FDA-approved for the
      indication of NVP. This review addresses the historical context, safety,
      efficacy, pharmacology, and practical role of doxylamine and pyridoxine for the
      management of NVP. The reintroduction of this doxylamine-pyridoxine combination
      pill into the American market fills a therapeutic gap in the management of NVP
      left by the removal of the same active drugs marketed over 30 years ago in the
      form of Bendectin. The substantial amount of safety data accumulated over the
      years makes it one of the few drugs that qualify for FDA Pregnancy Category A
      status. In the hierarchical approach to pharmacological treatment of NVP, the
      combination of doxylamine and pyridoxine should thus be first-tier. 

PMID- 24748823
TI  - Analysis of factors affecting rehospitalization of patients with chronic kidney
      disease after educational hospitalization.
AB  - BACKGROUND: Chronic kidney disease (CKD) is associated with a high risk of
      cardiovascular disease complications. Therefore, medical institutions conduct
      educational hospitalization for early treatment and education of CKD patients.
      However, patients who have been discharged after achieving educational targets
      can end up showing poor symptoms at home. There also have been several cases of
      rehospitalization or disease aggravation. In this study, we analyzed
      rehospitalized patients who were discharged from the hospital after CKD
      educational hospitalization and investigated the purpose of analyzing
      rehospitalization factors. MATERIALS AND METHODS: This was an observational case
      control study conducted at Yokosuka Kyousai Hospital. We performed univariate
      analysis using patient background features and laboratory data between a
      rehospitalization group and a no-rehospitalization group. Next, we performed
      multiple logistic regression analysis using the results of the univariate
      analysis. RESULTS: From the results of this study, we identified independent risk
      factors, such as serum albumin level, heart-failure complications, and estimated
      glomerular filtration rate (eGFR). Moreover, the serum Alb level was identified
      as the most important risk factor for rehospitalization. Therefore, we considered
      that it is important to live a life that makes it possible to maintain CKD stage
      G3b for a long time after discharge, because the cutoff level of eGFR is 31
      mL/minute/1.73 m(2). CONCLUSION: We believe that it is important to educate
      patients, their families, and medical staff on the importance of early detection
      and treatment, and we consider that this approach is important to inclusively
      protect the kidney.

PMID- 24748824
TI  - Results from an international multicenter trial evaluating the ease-of-use of and
      preference for a newly developed disposable injection pen for the treatment of
      growth hormone deficiency in treatment-naive children and adults.
AB  - Previous research has reported that ease of use of and preference for a delivery
      device are associated with greater patient compliance - an important factor in
      achieving optimal therapeutic results. The objective of this study was to assess
      the ease-of-use of a new disposable pen (GoQuick((r)), Pfizer, Inc.) versus the
      current reusable pen (GENOTROPIN Pen((r)), Pfizer, Inc.) to inject a daily dose
      of recombinant DNA origin human growth hormone, Genotropin((r)) (somatropin) in
      standard practice. In this randomized, crossover, multicenter, multinational,
      open-label study, ease-of-use of and preference for the two pens were assessed in
      three treatment-naive populations: 1) parents of very young children; 2) parent
      child dyads; and 3) adults via use of a validated self-report Injection Pen
      Assessment Questionnaire (IPAQ) after 2 months of at-home-use experience. The
      primary endpoint was the proportion of participants who reported the new
      disposable pen to be no different from or easier to use than the current reusable
      pen. Safety was also assessed and reported according to local legal requirements.
      Of the 120 screened patients, 119 were included in the ease-of-use analysis and
      all were included in the safety analyses. In all, 67.2% found the new somatropin
      disposable pen to be no different from or easier to use than the reusable pen
      (95% confidence interval: 58.8-75.7). Most adverse events were mild or moderate.
      No deaths or device- or treatment-related serious adverse events were reported.
      These results suggest that improvements made to the reusable somatropin pen are
      tangible and recognizable to treatment-naive patients and their caregivers, child
      caregiver dyads, and adults, and may positively impact continued compliance with
      therapy. REGISTRY INFORMATION: ClinicalTrials.gov identifier: NCT01112865.

PMID- 24748825
TI  - Sacroiliac joint pain: burden of disease.
AB  - OBJECTIVES: The sacroiliac joint (SIJ) is an important and significant cause of
      low back pain. We sought to quantify the burden of disease attributable to the
      SIJ. METHODS: The authors compared EuroQol 5D (EQ-5D) and Short Form (SF)-36
      based health state utility values derived from the preoperative evaluation of
      patients with chronic SIJ pain participating in two prospective clinical trials
      of minimally invasive SIJ fusion versus patients participating in a nationally
      representative USA cross-sectional survey (National Health Measurement Study
      [NHMS]). Comparative analyses controlled for age, sex, and oversampling in NHMS.
      A utility percentile for each SIJ subject was calculated using NHMS as a
      reference cohort. Finally, SIJ health state utilities were compared with
      utilities for common medical conditions that were published in a national utility
      registry. RESULTS: SIJ patients (number [n]=198) had mean SF-6D and EQ-5D utility
      scores of 0.51 and 0.44, respectively. Values were significantly depressed (0.28
      points for the SF-6D utility score and 0.43 points for EQ-5D; both P<0.0001)
      compared to NHMS controls. SIJ patients were in the lowest deciles for utility
      compared to the NHMS controls. The SIJ utility values were worse than those of
      many common, major medical conditions, and similar to those of other common
      preoperative orthopedic conditions. CONCLUSION: Patients with SIJ pain presenting
      for minimally invasive surgical care have marked impairment in quality of life
      that is worse than in many chronic health conditions, and this is similar to
      other orthopedic conditions that are commonly treated surgically. SIJ utility
      values are in the lowest two deciles when compared to control populations.

PMID- 24748826
TI  - Psychological therapies for the management of chronic pain.
AB  - Pain is a complex stressor that presents a significant challenge to most aspects
      of functioning and contributes to substantial physical, psychological,
      occupational, and financial cost, particularly in its chronic form. As medical
      intervention frequently cannot resolve pain completely, there is a need for
      management approaches to chronic pain, including psychological intervention.
      Psychotherapy for chronic pain primarily targets improvements in physical,
      emotional, social, and occupational functioning rather than focusing on
      resolution of pain itself. However, psychological therapies for chronic pain
      differ in their scope, duration, and goals, and thus show distinct patterns of
      treatment efficacy. These therapies fall into four categories: operant-behavioral
      therapy, cognitive-behavioral therapy, mindfulness-based therapy, and acceptance
      and commitment therapy. The current article explores the theoretical
      distinctiveness, therapeutic targets, and effectiveness of these approaches as
      well as mechanisms and individual differences that factor into treatment response
      and pain-related dysfunction and distress. Implications for future research,
      dissemination of treatment, and the integration of psychological principles with
      other treatment modalities are also discussed. 

PMID- 24748828
TI  - "It is the left eye, right?".
AB  - OBJECTIVE: Because wrong-site confusion is among the most common mistakes in the
      operations of paired organs, we have examined the frequency of wrong-sided
      confusions that could theoretically occur in cataract surgeries in the absence of
      preoperative verification. METHODS: Ten cataract surgeons participated in the
      study. The surgeons were asked to complete a questionnaire that included their
      demographic data, occupational habits, and their approach to and the handling of
      patients preoperatively. On the day of operation, the surgeons were asked to
      recognize the side of the operation from the patient's name only. At the second
      stage of the study, surgeons were asked to recognize the side of the operation
      while standing a 2-meter distance from the patient's face. The surgeons' answers
      were compared to the actual operation side. Patients then underwent a full time
      out procedure, which included side marking before the operation. RESULTS: Of the
      total 67 patients, the surgeons correctly identified the operated side of the eye
      in 49 (73%) by name and in 56 (83%) by looking at patients' faces. Wrong-side
      identification correlated with the time lapsed from the last preoperative
      examination (P=0.034). The number of cataract surgeries performed by the same
      surgeon (on the same day) also correlated to the number of wrong identifications
      (P=0.000). Surgeon seniority or age did not correlate to the number of wrong
      identifications. CONCLUSION: This study illustrates the high error rate that can
      result in the absence of side marking prior to cataract surgery, as well as in
      operations on other paired organs.

PMID- 24748827
TI  - The association between self-injurious behaviors and autism spectrum disorders.
AB  - A key area of concern in children with autism spectrum disorders (ASDs) are self
      injurious behaviors (SIBs). These are behaviors that an individual engages in
      that may cause physical harm, such as head banging, or self-biting. SIBs are more
      common in children with ASD than those who are typically developing or have other
      neurodevelopmental disabilities. Therefore, it is important that clinicians who
      work with children with ASD have a solid understanding of SIB. The purpose of
      this paper is to review the research on the epidemiology of SIB in children with
      ASD, factors that predict the presence of SIB in this population, and the
      empirically supported behavioral treatments available. 

PMID- 24748829
TI  - An innovative educational approach to professional development of medical
      laboratory scientists in Botswana.
AB  - PURPOSE: To address the shortage of laboratory scientists in Botswana, an
      innovative, one-year academic bridging program was initiated at the University of
      Botswana, to advance diploma-holding laboratory technicians towards becoming
      laboratory scientists holding Bachelor's degrees. An evaluation was conducted,
      which described the outcomes of the program and the lessons learned from this
      novel approach to meeting human resource needs. METHODS: This was a cross
      sectional, mixed-methods evaluation. Qualitative interviews were conducted with
      graduates of the Bachelor of Science (BSc) Medical Laboratory Sciences (MLS)
      bridging program, along with the graduates' current supervisors, and key
      informants who were involved in program development or implementation. The
      quantitative data collected included a written questionnaire, completed by
      program graduates, with a retrospective pre-test/post-test survey of graduates'
      confidence, in terms of key laboratory competencies. RESULTS: The BSc MLS
      bridging program produced thirty-three laboratory scientists over 3 years. There
      was a significant increase in confidence among graduates, for specified
      competencies, after the program (P<0.05). Graduates reported acquiring new skills
      and, often, accepting new responsibilities at their former workplace,
      particularly in relationship to leadership and management. Five graduates
      enrolled in advanced degree programs. Most graduates assumed increased
      responsibility. However, only two graduates were promoted after completing the
      training program. The lessons learned include: the importance of stakeholder
      involvement, the need for data to identify local needs, financial sustainability,
      catering for the needs of adult learners, and ensuring a technically challenging
      work environment, conducive to the application of skills learned during training.
      CONCLUSION: A strong public health and clinical laboratory system is essential
      for the rapid detection and control of emerging health threats, and for patient
      care. However, there is a need to adequately prepare laboratory human resources,
      to ensure efficient and effective laboratory services. Advancement of laboratory
      technicians towards becoming laboratory scientists, through a bridging program,
      can provide the necessary skills within a short time.

PMID- 24748830
TI  - Why are you here? Needs analysis of an interprofessional health-education
      graduate degree program.
AB  - Little is known about the nature of faculty development that is needed to meet
      calls for a focus on quality and safety with particular attention to the power of
      interprofessional collaborative practice. Through grounded-theory methodology,
      the authors describe the motivation and needs of 20 educator/clinicians in
      multiple disciplines who chose to enroll in an explicitly interprofessional
      master's program in health profession education. The results, derived from axial
      coding described by Strauss and Corbin, revealed that faculty pursue such
      postprofessional master's degrees out of a desire to be better prepared for their
      roles as educators. A hybrid-delivery model on campus and online provided access
      to graduate degrees while protecting the ability of participants to remain in
      current positions. The added benefit of a community of practice related to
      evidence-based and innovative models of education was valued by participants.
      Authentic, project-based learning and assessment supported their advancement in
      home institutions and systems. The experience was described by participants as a
      disruptive innovation that helped them attain their goal of leadership in health
      profession education. 

PMID- 24748831
TI  - AMP-activated protein kinase: An emerging target for ginseng.
AB  - The adenosine monophosphate (AMP)-activated protein kinase (AMPK) is a key sensor
      of cellular energy. Once activated, it switches on catabolic pathways generating
      adenosine triphosphate (ATP), while switching off biosynthetic pathways consuming
      ATP. Pharmacological activation of AMPK by metformin holds a therapeutic
      potential to reverse metabolic abnormalities such as type 2 diabetes and
      nonalcoholic fatty liver disease. In addition, altered metabolism of tumor cells
      is widely recognized and AMPK is a potential target for cancer prevention and/or
      treatment. Panax ginseng is known to be useful for treatment and/or prevention of
      cancer and metabolic diseases including diabetes, hyperlipidemia, and obesity. In
      this review, we discuss the ginseng extracts and ginsenosides that activate AMPK,
      we clarify the various mechanisms by which they achieve this, and we discuss the
      evidence that shows that ginseng or ginsenosides might be useful in the treatment
      and/or prevention of metabolic diseases and cancer. 

PMID- 24748832
TI  - Protective effect of ginsenoside Re on acute gastric mucosal lesion induced by
      compound 48/80.
AB  - The protective effect of ginsenoside Re, isolated from ginseng berry, against
      acute gastric mucosal lesions was examined in rats with a single intraperitoneal
      injection of compound 48/80 (C48/80). Ginsenoside Re (20 mg/kg or 100 mg/kg) was
      orally administered 0.5 h prior to C48/80 treatment. Ginsenoside Re dose
      dependently prevented gastric mucosal lesion development 3 h after C48/80
      treatment. Increases in the activities of myeloperoxidase (MPO; an index of
      neutrophil infiltration) and xanthine oxidase (XO) and the content of
      thiobarbituric acid reactive substances (TBARS; an index of lipid peroxidation)
      and decreases in the contents of hexosamine (a marker of gastric mucus) and
      adherent mucus, which occurred in gastric mucosal tissues after C48/80 treatment,
      were significantly attenuated by ginsenoside Re. The elevation of Bax expression
      and the decrease in Bcl2 expression after C48/80 treatment were also attenuated
      by ginsenoside Re. Ginsenoside Re significantly attenuated all these changes 3 h
      after C48/80 treatment. These results indicate that orally administered
      ginsenoside Re protects against C48/80-induced acute gastric mucosal lesions in
      rats, possibly through its stimulatory action on gastric mucus synthesis and
      secretion, its inhibitory action on neutrophil infiltration, and enhanced lipid
      peroxidation in the gastric mucosal tissue. 

PMID- 24748833
TI  - Free-fatty-acid-regulating effects of fermented red ginseng are mediated by
      hormones and by the autonomic nervous system.
AB  - BACKGROUND: Understanding what causes changes in the flux of free fatty acids
      (FFA) is important to elucidate the etiology of metabolic syndrome. The first aim
      of this study was to test whether or not hormones and the autonomic nervous
      system influence blood FFA levels. A secondary aim was to test by means of a
      multiple group path analysis whether the consumption of fermented red ginseng
      (FRG; Panax ginseng) would influence those causal relationships. METHODS: Ninety
      three postmenopausal women (age 50-73 yr) were randomly divided into two groups.
      One group (44 women; age, 58.4 +/- 5.9 yr; body mass index, 23.6 +/- 2.5 kg/m(2))
      was supplied placebo capsules and the other group (49 women, age 58.4 +/- 5.5 yr;
      body mass index, 22.9 +/- 2.4 kg/m(2)) was supplied FRG capsules. Both prior to
      and after the study (2 wk), blood samples were collected from the participants
      and several blood variables were measured and analyzed. RESULTS: Squared multiple
      correlations of FFA were 0.699 in the placebo group and 0.707 in the FRG group.
      The unstandardized estimate of estradiol (E2) for FFA was 0.824 in both groups.
      CONCLUSION: The path coefficients of cortisol and the branchial pulse for FFA
      were significantly different between the FRG group and the placebo group.

PMID- 24748834
TI  - Influence of Panax ginseng on obesity and gut microbiota in obese middle-aged
      Korean women.
AB  - BACKGROUND: Gut microbiota is regarded as one of the major factors involved in
      the control of body weight. The antiobesity effects of ginseng and its main
      constituents have been demonstrated, but the effects on gut microbiota are still
      unknown. METHODS: To investigate the effect of ginseng on gut microbiota, 10
      obese middle-aged Korean women took Panax ginseng extracts for 8 wk and
      assessment of body composition parameters, metabolic biomarkers, and gut
      microbiota composition was performed using 16S rRNA gene-based pyrosequencing at
      baseline and at 8 wk. Significant changes were observed in body weight and body
      mass index; however, slight changes were observed in gut microbiota. We divided
      the participants into two groups, the effective and the ineffective weight loss
      groups, depending on weight loss effect, in order to determine whether the
      antiobesity effect was influenced by the composition of gut microbiota, and the
      composition of gut microbiota was compared between the two groups. RESULTS: Prior
      to ginseng intake, significant differences of gut microbiota were observed
      between both at phyla and genera and the gut microbiota of the effective and
      ineffective weight loss groups was segregated on a principal coordinate analysis
      plot. CONCLUSION: Results of this study indicate that ginseng exerted a weight
      loss effect and slight effects on gut microbiota in all participants. In
      addition, its antiobesity effects differed depending on the composition of gut
      microbiota prior to ginseng intake.

PMID- 24748835
TI  - Re-evaluation of physicochemical and NMR data of triol ginsenosides Re, Rf, Rg2,
      and 20-gluco-Rf from Panax ginseng roots.
AB  - Ginseng roots were extracted with aqueous methanol, and extracts were suspended
      in water and extracted successively with ethyl acetate and n-butanol. Column
      chromatography using the n-butanol fraction yielded four purified triol ginseng
      saponins: the ginsenosides Re, Rf, Rg2, and 20-gluco-Rf. The physicochemical,
      spectroscopic, and chromatographic characteristics of the ginsenosides were
      measured and compared with reports from the literature. For spectroscopic
      analysis, two-dimensional nuclear magnetic resonance (NMR) methods such as (1)H
      (1)H correlation spectroscopy, nuclear Overhauser effect spectroscopy,
      heteronuclear single quantum correlation, and heteronuclear multiple bond
      connectivity were employed to identify exact peak assignments. Some peak
      assignments for previously published (1)H- and (13)C-NMR spectra were found to be
      inaccurate. This study reports the complete NMR assignment of 20-gluco-Rf for the
      first time. 

PMID- 24748836
TI  - Practical application of DNA markers for high-throughput authentication of Panax
      ginseng and Panax quinquefolius from commercial ginseng products.
AB  - Korean ginseng (Panax ginseng) and American ginseng (Panax quinquefolius) are
      widely used medicinal plants with similar morphology but different medicinal
      efficacy. Roots, flowers, and processed products of Korean and American ginseng
      can be difficult to differentiate from each other, leading to illegal trade in
      which one species is sold as the other. This study was carried out to develop
      convenient and reliable chloroplast genome-derived DNA markers for authentication
      of Korean and American ginseng in commercial processed products. One codominant
      marker could reproducibly identify both species and intentional mixtures of the
      two species. We further developed a set of species-unique dominant DNA markers.
      Each species-specific dominant marker could detect 1% cross contamination with
      other species by low resolution agarose gel electrophoresis or quantitative
      polymerase chain reaction. Both markers were successfully applied to evaluate the
      original species from various processed ginseng products purchased from markets
      in Korea and China. We believe that high-throughput application of this marker
      system will eradicate illegal trade and promote confident marketing for both
      species to increase the value of Korean as well as American ginseng in Korea and
      worldwide. 

PMID- 24748837
TI  - Evidence of genome duplication revealed by sequence analysis of multi-loci
      expressed sequence tag-simple sequence repeat bands in Panax ginseng Meyer.
AB  - BACKGROUND: Panax ginseng, the most famous medicinal herb, has a highly
      duplicated genome structure. However, the genome duplication of P. ginseng has
      not been characterized at the sequence level. Multiple band patterns have been
      consistently observed during the development of DNA markers using unique
      sequences in P. ginseng. METHODS: We compared the sequences of multiple bands
      derived from unique expressed sequence tag-simple sequence repeat (EST-SSR)
      markers to investigate the sequence level genome duplication. RESULTS:
      Reamplification and sequencing of the individual bands revealed that, for each
      marker, two bands around the expected size were genuine amplicons derived from
      two paralogous loci. In each case, one of the two bands was polymorphic, showing
      different allelic forms among nine ginseng cultivars, whereas the other band was
      usually monomorphic. Sequences derived from the two loci showed a high
      similarity, including the same primer-binding site, but each locus could be
      distinguished based on SSR number variations and additional single nucleotide
      polymorphisms (SNPs) or InDels. A locus-specific marker designed from the SNP
      site between the paralogous loci produced a single band that also showed clear
      polymorphism among ginseng cultivars. CONCLUSION: Our data imply that the recent
      genome duplication has resulted in two highly similar paralogous regions in the
      ginseng genome. The two paralogous sequences could be differentiated by large SSR
      number variations and one or two additional SNPs or InDels in every 100 bp of
      genic region, which can serve as a reliable identifier for each locus.

PMID- 24748838
TI  - Antagonistic Bacillus species as a biological control of ginseng root rot caused
      by Fusarium cf. incarnatum.
AB  - BACKGROUND: This study aimed to develop a biocontrol system for ginseng root rot
      caused by Fusarium cf. incarnatum. METHODS: In total, 392 bacteria isolated from
      ginseng roots and various soils were screened for their antifungal activity
      against the fungal pathogen, and a bacterial isolate (B2-5) was selected as a
      promising candidate for the biocontrol because of the strong antagonistic
      activity of the bacterial cell suspension and culture filtrate against pathogen.
      RESULTS: The bacterial isolate B2-5 displayed an enhanced inhibitory activity
      against the pathogen mycelial growth with a temperature increase to 25 degrees C,
      produced no pectinase (related to root rotting) and no critical rot symptoms at
      low [10(6) colony-forming units (CFU)/mL] and high (10(8) CFU/mL) inoculum
      concentrations. In pot experiments, pretreatment with the bacterial isolate in
      the presumed optimal time for disease control reduced disease severity
      significantly with a higher control efficacy at an inoculum concentration of
      10(6) CFU/mL than at 10(8) CFU/mL. The establishment and colonization ability of
      the bacterial isolates on the ginseng rhizosphere appeared to be higher when both
      the bacterial isolate and the pathogen were coinoculated than when the bacterial
      isolate was inoculated alone, suggesting its target-oriented biocontrol activity
      against the pathogen. Scanning electron microscopy showed that the pathogen
      hyphae were twisted and shriveled by the bacterial treatment, which may be a
      symptom of direct damage by antifungal substances. CONCLUSION: All of these
      results suggest that the bacterial isolate has good potential as a microbial
      agent for the biocontrol of the ginseng root rot caused by F. cf. incarnatum.

PMID- 24748839
TI  - Effects of extrusion cooking on physicochemical properties of white and red
      ginseng (powder).
AB  - A systematic comparison of the physicochemical properties of white ginseng (WG),
      extruded white ginseng (EWG), red ginseng (RG), and extruded red ginseng (ERG)
      was performed. The aim of the present study was to identify the effects of the
      physicochemical properties of ginseng by extrusion cooking. The highest value of
      the water absorption index (WAI) was 3.64 g/g obtained from EWG, and the highest
      value of the water solubility index (WSI) was 45.27% obtained from ERG. The ERG
      had a better dispersibility compared with other samples. Extrusion cooking led to
      a significant increase in acidic polysaccharide and total sugar content but
      resulted in a decrease in crude fat and reducing sugar contents. Enzyme treatment
      led to a sharp increase in acidic polysaccharide content, especially the
      cellulose enzyme. Extrusion cooking led to a significant increase in 2,2-diphenyl
      1-picrylhydrazyl (DPPH) radical scavenging activity and reducing power, and the
      increases in WG and RG were 13.56% (0.038) and 3.56% (0.026), respectively. The
      data of this study provide valuable information about the effects of extrusion on
      quality changes of EWG and ERG. 

PMID- 24748840
TI  - Processed Vietnamese ginseng: Preliminary results in chemistry and biological
      activity.
AB  - BACKGROUND: This study was carried out to investigate the effect of the steaming
      process on chemical constituents, free radical scavenging activity, and
      antiproliferative effect of Vietnamese ginseng. METHODS: Samples of powdered
      Vietnamese ginseng were steamed at 120 degrees C for various times and their
      extracts were subjected to chemical and biological studies. RESULTS: Upon
      steaming, contents of polar ginsenosides, such as Rb1, Rc, Rd, Re, and Rg1, were
      rapidly decreased, whereas less polar ginsenosides such as Rg3, Rg5, Rk1, Rk3,
      and Rh4 were increased as reported previously. However, ocotillol type saponins,
      which have no glycosyl moiety at the C-20 position, were relatively stable on
      steaming. The radical scavenging activity was increased continuously up to 20 h
      of steaming. Similarly, the antiproliferative activity against A549 lung cancer
      cells was also increased. CONCLUSION: It seems that the antiproliferative
      activity is closely related to the contents of ginsenoside Rg3, Rg5, and Rk1.

PMID- 24748842
TI  - Intra- and inter-observer reliability in selection of the heart rate deflection
      point during incremental exercise: comparison to a computer-generated deflection
      point.
AB  - This study was designed to 1) determine the relative frequency of occurrence of a
      heart rate deflection point (HRDP), when compared to a linear relationship,
      during progressive exercise, 2) measure the reproducibility of a visual
      assessment of a heart rate deflection point (HRDP), both within and between
      observers 3) compare visual and computer-assessed deflection points. Subjects
      consisted of 73 competitive male cyclists with mean age of 31.4 +/- 6.3 years,
      mean height 178.3 +/- 4.8 cm. and weight 74.0 +/- 4.4 kg. Tests were conducted on
      an electrically-braked cycle ergometer beginning at 25 watts and progressing 25
      watts per minute to fatigue. Heart Rates were recorded the last 10 seconds of
      each stage and at fatigue. Scatter plots of heart rate versus watts were computer
      generated and given to 3 observers on two different occasions. A computer program
      was developed to assess if data points were best represented by a single line or
      two lines. The HRDP represented the intersection of the two lines. Results of
      this study showed that 1) computer-assessed HRDP showed that 44 of 73 subjects
      (60.3%) had scatter plots best represented by a straight line with no HRDP 2)in
      those subjects having HRDP, all 3 observers showed significant differences(p =
      0.048, p = 0.007, p = 0.001) in reproducibility of their HRDP selection.
      Differences in HRDP selection were significant for two of the three comparisons
      between observers (p = 0.002, p = 0.305, p = 0.0003) Computer-generated HRDP was
      significantly different than visual HRDP for 2 of 3 observers (p = 0.0016, p =
      0.513, p = 0.0001). It is concluded that 1) HRDP occurs in a minority of subjects
      2) significant differences exist, both within and between observers, in selection
      of HRDP and 3) differences in agreement between visual and computer-generated
      HRDP would indicate that, when HRDP exists, it should be computer-assessed. 

PMID- 24748843
TI  - Influence of moderate training on gait and work capacity of fibromyalgia
      patients: a preliminary field study.
AB  - This field study examined the influence of moderate intensity training on gait
      patterns and work capacity of individuals with fibromyalgia syndrome (FS). FS is
      a chronic condition of unknown etiology, characterized by muscle tenderness, pain
      and stiffness and often accompanied by depression and fatigue which seems to
      occur primarily in middle aged females. There is no known cure for FS but
      treatment often includes a prescription of mild exercise. Few studies have
      evaluated the effectiveness of mild exercise on work capacity and gait patterns
      in FS patients. Participants were 14 females (age 47.0 +/- 7.6 y) who
      participated in a 10 wk community based aerobic, strength and stretching program
      designed for FS individuals. Subjects were evaluated pre- and post-program and at
      a 2 month follow up. Work capacity was estimated by a sub-maximal PWC 170 cycle
      ergometer test and a Borg perceived exertion scale. Gait was assessed using
      OptoTrack three dimensional kinematics with 16 channel analogue data acquisition
      system. Trunk flexibility was also assessed. No significant change in estimated
      work capacity or flexibility was seen between pre- post- and follow up times.
      Nevertheless, a significant increase in self selected walking speed (p < 0.05)
      and a trend toward a more normal gait pattern that was sustained in the follow up
      testing was noted. We had previously also reported a significant improvement in
      muscle pain and other fibromyalgia symptoms in this population consequent to the
      training program. It was concluded that mild exercise training that does not
      influence work capacity or trunk flexibility can nevertheless positively
      influence gait mechanics and fibromyalgia symptoms in female FS patients. 

PMID- 24748841
TI  - Exercise-induced signal transduction and gene regulation in skeletal muscle.
AB  - Skeletal muscle adapts to various forms of exercise depending on the force, speed
      and duration characteristics of the contraction pattern. The stresses and signals
      associated with each contraction pattern are likely to specifically activate a
      network of signal transduction pathways that integrate this information. These
      pathways include the calcineurin, Calcium/calmodulin-dependent protein kinase
      (CaMK), mitogen-activated protein kinase (MAPK), protein kinase C (PKC), nuclear
      factor kappa B (NF-kappaB), AMP-dependent protein kinase (AMPK), insulin
      signalling and developmental pathways. Activated signal transduction pathways
      activate or increase the expression of transcription factors via various
      mechanisms. Skeletal muscle genes are usually regulated by combinatorial control
      exerted by several transcription factors and possibly other mechanisms. In
      addition, adaptations such as an increase in mitochondrial biogenesis or the
      activation of satellite cell proliferation involve distinct regulatory
      mechanisms. 

PMID- 24748844
TI  - Physiological changes in sixth graders who trained to walk the Boston marathon.
AB  - The purpose of this study was to assess if supervised, low intensity training
      would improve aerobic capacity and body composition in sixth graders. Twelve
      sixth graders walk-trained at approximately 50% of their maximal heart rate, four
      to five days/week for 12 weeks; beginning with an average of 10 miles/week and
      increasing to about 27 miles/week (Experimental group [E]). Six subjects of
      similar age volunteered to be controls (Control group [C]). Baseline and
      post?training measurements included: height (cm), body weight (kg), sum of
      skinfolds at six sites (mm), and maximal oxygen consumption (VO2max; ml.kg(
      1).min(-1)). Three-day dietary records were also collected at pre-, mid-, and
      post-training to assess dietary changes that may have occurred during the study.
      There were significant increases (p < 0.05) from baseline to post-training in
      both groups in height and body weight. There was a significant interaction in the
      sum of skinfolds: E decreased 10.3% (p < 0.05) and C increased 2.3% (p > 0.05).
      There were no significant differences between groups in relative VO2max (ml.kg(
      1)min(-1)) from baseline to post-training. C consumed significantly more total
      kilojoules (11,577 +/- 3883 [C]; 7431 +/- 2523 [E]) and more total grams of
      carbohydrate (392 +/- 403 [C]; 227 +/- 48 [E]) and fat (93 +/- 97 [C]; 62 +/- 29
      [E]) than E, post-training. C also consumed significantly more total grams of
      protein than E pre-training (95 +/- 99 [C]; 74 +/- 21 [E]). In conclusion, walk
      training elicited a significant decrease in sum of skinfolds with no change in
      relative VO2max. Furthermore, no dietary changes were observed in the
      experimental group as a result of the training. 

PMID- 24748845
TI  - Effect of time of day on the relationship between lactate and ventilatory
      thresholds: a brief report.
AB  - The purpose of this investigation was to study the effect of time of day on the
      relationship between lactate (LT) and ventilatory thresholds (VT) of pulmonary
      oxygen uptake (VO2). Seven moderately active male volunteers (26.3 +/- 3.0 years,
      1.74 +/- 0.08 m, 76 +/- 5 kg) performed a maximal incremental test (increases of
      30 W every 2 min) on a cycle ergometer on consecutive days at 0900 h, 1400h and
      1900 h in a randomized fashion. The anaerobic threshold was determined using both
      ventilatory gas analysis and blood lactate measures. Each of the following
      variables was recorded both at VT and the LT; heart rate (HR, beats.min(-1)),
      minute ventilation (VE, L.min(-1)), respiratory exchange ratio (RER), time to
      threshold (Time, sec), oxygen uptake (VO2, ml.kg(-1).min(-1)) and VO2 as a
      percentage of maximal oxygen uptake (%VO2max). The correlations between VT and LT
      variables analyzed by Pearson product moment correlations for each time of day.
      ANOVA was used to compare the data obtained at different times of the day. There
      were no significant differences for the data related to time of day either for
      ventilatory gas analysis or lactate measurements. The correlation coefficients
      between VT and LT variables were moderate to high (r=0.56-0.94) for time of day.
      However, the correlations for HR, VO2, and %VO2max (r=0.81-0.94) were slightly
      stronger compared with Time, VE and RER (r=0.56-0.88). It was concluded that, the
      data at VT and LT were not influenced by time of day. 

PMID- 24748846
TI  - Caveolin-3 is Up-Regulated in the Physiological Left Ventricular Hypertrophy
      Induced by Voluntary Exercise Training in Rats.
AB  - Various substances have been introduced in relation with cardiac hypertrophy
      almost always with controversy in their roles in signal transduction. Those
      controversies may attribute to the diversity of cardiac hypertrophy. We
      previously showed that calcineurin was activated in physiological left
      ventricular hypertrophy (LVH) induced by voluntary exercise training, but not in
      decompensated pressure-overload LVH. In the current study, we advanced our search
      for the differences between the voluntary exercise-induced LVH and the pressure
      overload LVH into several other hypertrophy-related substances including
      caveolin. Wistar rats were assigned to one of the following three groups: 10
      weeks of voluntary exercise (EX), sedentary regimen (SED), and 4 weeks of
      ascending aortic constriction (AC). The EX rats voluntarily ran 1.6 +/- 1.1
      km/day in the specially manufactured cages resulting in LVH (24 % increase in
      left ventricular weight per body weight ratio). Myocardial tissue homogenate of
      the EX rats revealed different characteristics in signal transduction of
      hypertrophy from that of the AC. The EX rats had normal sarcoplasmic reticulum
      (SR) Ca(2+)ATPase mRNA level and normal myosin heavy chain isozyme pattern
      assessed by RNA protection assay, while AC rats had decreased SR Ca(2+)ATPase
      mRNA level and increased beta myosin heavy chain mRNA level. Myocardial caveolin
      3 protein levels assessed by Western blotting increased in the EX rats but
      decreased in the AC rats. The voluntary exercise-induced LVH differed in signal
      transduction from the decompensated pressure-overload LVH. Caveolin-3 was induced
      in the voluntary exercise-induced LVH, while it was decreased in the
      decompensated pressure-overload LVH. 

PMID- 24748847
TI  - Physiological responses during matches and profile of elite pencak silat
      exponents.
AB  - This is a descriptive, cross-sectional study describing the physiological
      responses during competitive matches and profile of elite exponents of an
      emerging martial art sport, pencak silat. Thirty exponents (21 males and 9
      females) were involved in the study. Match responses (i.e. heart rate (HR)
      throughout match and capillary blood lactate concentration, [La], at pre-match
      and at the end of every round) were obtained during actual competitive duels.
      Elite silat exponents' physiological attributes were assessed via anthropometry,
      vertical jump, isometric grip strength, maximal oxygen uptake, and the Wingate 30
      s anaerobic test of the upper and lower body, in the laboratory. The match
      response data showed that silat competitors' mean HR was > 84% of estimated HR
      maximum and levels of [La] ranged from 6.7 - 18.7 mMol(-1) during matches. This
      suggests that competitive silat matches are characterised by high aerobic and
      anaerobic responses. In comparison to elite taekwondo and judo athletes'
      physiological characteristics, elite silat exponents have lower aerobic fitness
      and grip strength, but greater explosive leg power (vertical jump). Generally,
      they also possessed a similar anaerobic capability in the lower but markedly
      inferior anaerobic capability in the upper body. 

PMID- 24748848
TI  - Grain boundary excess volume and defect annealing of copper after high-pressure
      torsion.
AB  - The release of excess volume upon recrystallization of ultrafine-grained Cu
      deformed by high-pressure torsion (HPT) was studied by means of the direct
      technique of high-precision difference dilatometry in combination with
      differential scanning calorimetry (DSC) and scanning electron microscopy. From
      the length change associated with the removal of grain boundaries in the wake of
      crystallite growth, a structural key quantity of grain boundaries, the grain
      boundary excess volume or expansion [Formula: see text] m was directly
      determined. The value is quite similar to that measured by dilatometry for grain
      boundaries in HPT-deformed Ni. Activation energies for crystallite growth of
      [Formula: see text] and [Formula: see text] are derived by Kissinger analysis
      from dilatometry and DSC data, respectively. In contrast to Ni, substantial
      length change proceeds in Cu at elevated temperatures beyond the regime of
      dominant crystallite growth. In the light of recent findings from tracer
      diffusion and permeation experiments, this is associated with the shrinkage of
      nanovoids at high temperatures.

PMID- 24748849
TI  - What young people want from health-related online resources: a focus group study.
AB  - The growth of the Internet as an information source about health, particularly
      amongst young people, is well established. The aim of this study was to explore
      young people's perceptions and experiences of engaging with health-related online
      content, particularly through social media websites. Between February and July
      2011 nine focus groups were facilitated across Scotland with young people aged
      between 14 and 18 years. Health-related user-generated content seems to be
      appreciated by young people as a useful, if not always trustworthy, source of
      accounts of other people's experiences. The reliability and quality of both user
      generated content and official factual content about health appear to be concerns
      for young people, and they employ specialised strategies for negotiating both
      areas of the online environment. Young people's engagement with health online is
      a dynamic area for research. Their perceptions and experiences of health-related
      content seem based on their wider familiarity with the online environment and, as
      the online environment develops, so too do young people's strategies and
      conventions for accessing it.

PMID- 24748850
TI  - Zebrafish Assays as Developmental Toxicity Indicators in The Design of TAML
      Oxidation Catalysts.
AB  - TAML activators promise a novel water treatment approach by efficiently
      catalysing peroxide-based degradation of chemicals of high concern at
      environmental concentrations. Green design ethics demands an exploration of TAML
      toxicity. Exposure to high concentrations of certain activators caused adverse
      effects in zebrafish. At typical TAML operational concentrations, development was
      not perturbed.

PMID- 24748851
TI  - Molecular and Phenetic Characterization of the Bacterial Assemblage of Hot Lake,
      WA, an Environment with High Concentrations of Magnesium Sulfate, and Its
      Relevance to Mars.
AB  - Hot Lake (Oroville, WA) is an athalassohaline epsomite lake that can have
      precipitating concentrations of MgSO4 salts, mainly epsomite. Little biotic study
      has been done on epsomite lakes and it was unclear whether microbes isolated from
      epsomite lakes and their margins would fall within recognized halotolerant
      genera, common soil genera, or novel phyla. Our initial study cultivated and
      characterized epsotolerant bacteria from the lake and its margins. Approximately
      100 aerobic heterotrophic microbial isolates were obtained by repetitive streak
      plating in high-salt media including either 10% NaCl or 2 M MgSO4. The collected
      isolates were all bacteria, nearly evenly divided between Gram-positive and Gram
      negative clades, the most abundant genera being Halomonas, Idiomarina,
      Marinobacter, Marinococcus, Nesterenkonia, Nocardiopsis, and Planococcus.
      Bacillus, Corynebacterium, Exiguobacterium, Kocuria, and Staphylococcus also were
      cultured. This initial study included culture-independent community analysis of
      direct DNA extracts of lake margin soil using PCR-based clone libraries and 16S
      rRNA gene phylogeny. Clones assigned Gram-positive bacterial clades (70% of total
      clones) were dominated by sequences related to uncultured actinobacteria. There
      were abundant Deltaproteobacteria clones related to bacterial sulfur metabolisms
      and clones of Legionella and Coxiella. These epsomite lake microbial communities
      seem to be divided between bacteria primarily associated with hyperhaline
      environments rich in NaCl and salinotolerant relatives of common soil organisms.
      Archaea appear to be in low abundance and none were isolated, despite near
      saturated salinities. Growth of microbes at very high concentrations of magnesium
      and other sulfates has relevance to planetary protection and life-detection
      missions to Mars, where scant liquid water may form as deliquescent brines and
      appear as eutectic liquids.

PMID- 24748852
TI  - Variational Optimization of an All-Atom Implicit Solvent Force Field to Match
      Explicit Solvent Simulation Data.
AB  - The development of accurate implicit solvation models with low computational cost
      is essential for addressing many large-scale biophysical problems. Here, we
      present an efficient solvation term based on a Gaussian solvent-exclusion model
      (EEF1) for simulations of proteins in aqueous environment, with the primary aim
      of having a good overlap with explicit solvent simulations, particularly for
      unfolded and disordered states - as would be needed for multiscale applications.
      In order to achieve this, we have used a recently proposed coarse-graining
      procedure based on minimization of an entropy-related objective function to train
      the model to reproduce the equilibrium distribution obtained from explicit water
      simulations. Via this methodology, we have optimized both a charge screening
      parameter and a backbone torsion term against explicit solvent simulations of an
      alpha-helical and a beta-stranded peptide. The performance of the resulting
      effective energy function, termed EEF1-SB, is tested with respect to the
      properties of folded proteins, the folding of small peptides or fast-folding
      proteins, and NMR data for intrinsically disordered proteins. The results show
      that EEF1-SB provides a reasonable description of a wide range of systems, but
      its key advantage over other methods tested is that it captures very well the
      structure and dimension of disordered or weakly structured peptides. EEF1-SB is
      thus a computationally inexpensive (~ 10 times faster than Generalized-Born
      methods) and transferable approximation for treating solvent effects.

PMID- 24748853
TI  - High performance p-type organic thin film transistors with an intrinsically
      photopatternable, ultrathin polymer dielectric layer.
AB  - A high-performing bottom-gate top-contact pentacene-based oTFT technology with an
      ultrathin (25-48 nm) and electrically dense photopatternable polymeric gate
      dielectric layer is reported. The photosensitive polymer poly((+/-)endo,exo
      bicyclo[2.2.1]hept-5-ene-2,3-dicarboxylic acid, diphenylester) (PNDPE) is
      patterned directly by UV-exposure (lambda = 254 nm) at a dose typical for
      conventionally used negative photoresists without the need for any additional
      photoinitiator. The polymer itself undergoes a photo-Fries rearrangement reaction
      under UV illumination, which is accompanied by a selective cross-linking of the
      macromolecules, leading to a change in solubility in organic solvents. This
      crosslinking reaction and the negative photoresist behavior are investigated by
      means of sol-gel analysis. The resulting transistors show a field-effect mobility
      up to 0.8 cm2 V-1 s-1 at an operation voltage as low as -4.5 V. The ultra-low
      subthreshold swing in the order of 0.1 V dec-1 as well as the completely
      hysteresis-free transistor characteristics are indicating a very low interface
      trap density. It can be shown that the device performance is completely stable
      upon UV-irradiation and development according to a very robust chemical
      rearrangement. The excellent interface properties, the high stability and the
      small thickness make the PNDPE gate dielectric a promising candidate for fast
      organic electronic circuits.

PMID- 24748854
TI  - A default prior distribution for contingency tables with dependent factor levels.
AB  - A default prior distribution is proposed for the Bayesian analysis of contingency
      tables. The prior is specified to allow for dependence between levels of the
      factors. Different dependence structures are considered, including conditional
      autoregressive and distance correlation structures. To demonstrate the prior
      distribution, a dataset is considered which involves estimating the number of
      injecting drug users in the eleven National Health Service board regions of
      Scotland using an incomplete contingency table where the dependence structure
      relates to geographical regions.

PMID- 24748855
TI  - Editor's Introduction to This Issue.

PMID- 24748856
TI  - Next-generation sequencing and epigenomics research: a hammer in search of nails.
AB  - After the initial enthusiasm of the human genome project, it became clear that
      without additional data pertaining to the epigenome, i.e., how the genome is
      marked at specific developmental periods, in different tissues, as well as across
      individuals and species-the promise of the genome sequencing project in
      understanding biology cannot be fulfilled. This realization prompted several
      large-scale efforts to map the epigenome, most notably the Encyclopedia of DNA
      Elements (ENCODE) project. While there is essentially a single genome in an
      individual, there are hundreds of epigenomes, corresponding to various types of
      epigenomic marks at different developmental times and in multiple tissue types.
      Unprecedented advances in next-generation sequencing (NGS) technologies, by
      virtue of low cost and high speeds that continue to improve at a rate beyond what
      is anticipated by Moore's law for computer hardware technologies, have
      revolutionized molecular biology and genetics research, and have in turn prompted
      innovative ways to reduce the problem of measuring cellular events involving DNA
      or RNA into a sequencing problem. In this article, we provide a brief overview of
      the epigenome, the various types of epigenomic data afforded by NGS, and some of
      the novel discoveries yielded by the epigenomics projects. We also provide ample
      references for the reader to get in-depth information on these topics. 

PMID- 24748858
TI  - Interactive Visualization for Patient-to-Patient Comparison.
AB  - A visual analysis approach and the developed supporting technology provide a
      comprehensive solution for analyzing large and complex integrated genomic and
      biomedical data. This paper presents a methodology that is implemented as an
      interactive visual analysis technology for extracting knowledge from complex
      genetic and clinical data and then visualizing it in a meaningful and
      interpretable way. By synergizing the domain knowledge into development and
      analysis processes, we have developed a comprehensive tool that supports a
      seamless patient-to-patient analysis, from an overview of the patient population
      in the similarity space to the detailed views of genes. The system consists of
      multiple components enabling the complete analysis process, including data
      mining, interactive visualization, analytical views, and gene comparison. We
      demonstrate our approach with medical scientists on a case study of childhood
      cancer patients on how they use the tool to confirm existing hypotheses and to
      discover new scientific insights. 

PMID- 24748857
TI  - Membrane Proteins Involved in Epithelial-Mesenchymal Transition and Tumor
      Invasion: Studies on TMPRSS4 and TM4SF5.
AB  - The epithelial-mesenchymal transition (EMT) is one mechanism by which cells with
      mesenchymal features can be generated and is a fundamental event in
      morphogenesis. Recently, invasion and metastasis of cancer cells from the primary
      tumor are now thought to be initiated by the developmental process termed the
      EMT, whereby epithelial cells lose cell polarity and cell-cell interactions, and
      gain mesenchymal phenotypes with increased migratory and invasive properties. The
      EMT is believed to be an important step in metastasis and is implicated in cancer
      progression, although the influence of the EMT in clinical specimens has been
      debated. This review presents the recent results of two cell surface proteins,
      the functions and underlying mechanisms of which have recently begun to be
      demonstrated, as novel regulators of the molecular networks that induce the EMT
      and cancer progression. 

PMID- 24748859
TI  - Semantic Modeling for SNPs Associated with Ethnic Disparities in HapMap Samples.
AB  - Single-nucleotide polymorphisms (SNPs) have been emerging out of the efforts to
      research human diseases and ethnic disparities. A semantic network is needed for
      in-depth understanding of the impacts of SNPs, because phenotypes are modulated
      by complex networks, including biochemical and physiological pathways. We
      identified ethnicity-specific SNPs by eliminating overlapped SNPs from HapMap
      samples, and the ethnicity-specific SNPs were mapped to the UCSC RefGene lists.
      Ethnicity-specific genes were identified as follows: 22 genes in the USA (CEU)
      individuals, 25 genes in the Japanese (JPT) individuals, and 332 genes in the
      African (YRI) individuals. To analyze the biologically functional implications
      for ethnicity-specific SNPs, we focused on constructing a semantic network model.
      Entities for the network represented by "Gene," "Pathway," "Disease," "Chemical,"
      "Drug," "ClinicalTrials," "SNP," and relationships between entity-entity were
      obtained through curation. Our semantic modeling for ethnicity-specific SNPs
      showed interesting results in the three categories, including three diseases
      ("AIDS-associated nephropathy," "Hypertension," and "Pelvic infection"), one drug
      ("Methylphenidate"), and five pathways ("Hemostasis," "Systemic lupus
      erythematosus," "Prostate cancer," "Hepatitis C virus," and "Rheumatoid
      arthritis"). We found ethnicity-specific genes using the semantic modeling, and
      the majority of our findings was consistent with the previous studies - that an
      understanding of genetic variability explained ethnicity-specific disparities. 

PMID- 24748860
TI  - Identification of ethnically specific genetic variations in pan-asian ethnos.
AB  - Asian populations contain a variety of ethnic groups that have ethnically
      specific genetic differences. Ethnic variants may be highly relevant in disease
      and human differentiation studies. Here, we identified ethnically specific
      variants and then investigated their distribution across Asian ethnic groups. We
      obtained 58,960 Pan-Asian single nucleotide polymorphisms of 1,953 individuals
      from 72 ethnic groups of 11 Asian countries. We selected 9,306 ethnic variant
      single nucleotide polymorphisms (ESNPs) and 5,167 ethnic variant copy number
      polymorphisms (ECNPs) using the nearest shrunken centroid method. We analyzed
      ESNPs and ECNPs in 3 hierarchical levels: superpopulation, subpopulation, and
      ethnic population. We also identified ESNP- and ECNP-related genes and their
      features. This study represents the first attempt to identify Asian ESNP and ECNP
      markers, which can be used to identify genetic differences and predict disease
      susceptibility and drug effectiveness in Asian ethnic populations. 

PMID- 24748861
TI  - Cephalic duodenopancreatectomy for hyperalgic duodenal Crohn's disease fistulized
      in the pancreatic gland.
AB  - Upper gastrointestinal (GI) tract involvement in adult Crohn's disease (CD) is
      rare and severe complications unusual. Stenosis has been reported, but
      gastroduodenal fistulae are seldom detected during surgery and most of the
      fistulae are cologastric or ileogastric. In complicated gastroduodenal CD,
      medical treatments are often effective and surgery is only considered in
      exceptional cases. We here report the unusual case of a 23-year-old patient with
      upper GI CD presenting a hyperalgic giant ulcer of the bulb fistulized in the
      pancreatic gland. The failure of steroids and two lines of combined treatment led
      us to a salvage surgical option. Abdominal exploration showed a plate stomach
      with an inflammatory bulboduodenal block. Cephalic duodenopancreatectomy and
      cholecystectomy were performed; histological analysis reported large fissuring
      pylorus ulceration with micro abscesses reaching the pancreas and the presence of
      non-caseating granulomas. Six months after the surgery, the patient had stopped
      antalgic treatment and did not have residual abdominal pain. He had gained 11 kg
      in weight and had no diarrhea with pancreatic enzymes. To our knowledge, we
      report the first case of an upper GI and fistulizing CD patient heavily treated
      with steroids and combined immunosuppressant agents requiring salvage cephalic
      duodenopancreatectomy. 

PMID- 24748862
TI  - Gastric metastasis of lung cancer mimicking an adrenal tumor.
AB  - Lung cancer is one of the leading causes of cancer deaths worldwide. Metastatic
      spreads of lung cancer are often found in the adrenal glands, bone, liver, brain
      and kidneys; the gastrointestinal tract is less commonly involved. However,
      according to some reports in the literature, the incidence of gastrointestinal
      metastases, most of them asymptomatic, might be as frequent as 11% in autopsy
      studies of lung cancer, which suggests that this condition is not as rare as it
      was previously considered. We report a very rare case of small cell lung cancer
      with a solitary gastric metastasis mimicking an adrenal tumor which was belatedly
      diagnosed due to its unusual presentation and treated actively with surgery and
      chemotherapy, achieving a relatively favorable outcome. 

PMID- 24748863
TI  - Two Japanese cases of birt-hogg-dube syndrome with pulmonary cysts,
      fibrofolliculomas, and renal cell carcinomas.
AB  - Birt-Hogg-Dube syndrome (BHD) is a rare autosomal dominant inherited disease
      caused by a germline mutation in the folliculin gene mapped in the region of
      chromosome 17p11.2. BHD predisposes the patient to cutaneous fibrofolliculomas
      (FFs), pulmonary cysts (PCs), and renal cell carcinoma (RC). Here, we present two
      cases of BHD in Japanese patients. One patient was a 37-year-old female, and the
      other a 35-year-old male. Each of the patients was affected by all three symptoms
      of BHD. Both patients had unremarkable FFs, asymptomatic PCs, and asymptomatic
      RC. The presence of RC was revealed by abdominal ultrasonic examination. We also
      summarized the data from 62 Asian cases of BHD from the available literature and
      found that their FFs were unremarkable. In addition, the proportion of BHD
      patients with FF is smaller for Asian patients than it is for Caucasian patients.
      We also found that it is rare for BHD patients in Asia to show all three symptoms
      of BHD. Careful inspection of the skin as well as skin biopsies are important for
      the early detection of BHD cases in Asia. 

PMID- 24748864
TI  - Long-Term Remission of an Aggressive Sebaceous Carcinoma following Chemotherapy.
AB  - Sebaceous carcinoma (SC) is an uncommon neoplasm manifesting itself either in the
      eyelid or extraocularly in the head and neck area. Surgery is the standard of
      care. Irradiation is rarely proposed as monotherapy but is frequently
      administered as an adjuvant regimen following surgical resection. There is no
      known strategy concerning chemotherapeutic treatment in highly aggressive
      recurrent - or metastatic - forms of the disease. Our patient presented with an
      aggressive SC of the scalp recurring after multiple excisions and local
      radiotherapy. Chemotherapy with 5-fluorouracil, cisplatin and docetaxel was then
      initiated; 4 cycles were administered, followed by capecitabine maintenance.
      Shortly after starting chemotherapy, dermal lesions had completely disappeared
      and radiological response could be seen. The patient experienced an extended
      period (>20 months) of complete remission. In this report, we show an excellent
      response of a highly aggressive SC after a combination of chemotherapy as for
      head and neck cancers. 

PMID- 24748865
TI  - Endocardial Invasion of Lung Cancer Undiagnosable before Autopsy.
AB  - A 59-year-old male patient presented with left chest discomfort on admission. His
      medical history included encephalitis in childhood and his smoking history was 20
      cigarettes per day for 40 years. A physical examination showed an anemic and
      edematous face with weak respiratory sounds in the left lung. The patient had
      elevated calcium levels and decreased hemoglobin and potassium. His parathyroid
      hormone-related protein level was elevated. Thoracic radiography showed
      cardiomegaly and computed tomography revealed a left lung mass with invasion of
      the heart and pleural effusion. Magnetic resonance imaging showed endocardial
      invasion of the tumor mass. Gallium-68 imaging revealed positive accumulation in
      the region surrounding the heart. No diagnoses were possible upon frequent
      cytology of his sputum and pleural effusion. The patient died from congestive
      heart failure with anoxia 38 days after admission. An autopsy revealed tumoral
      mass occlusion in the left main bronchus and tumoral invasion of the left atrium,
      left ventricle, and aorta. 

PMID- 24748866
TI  - Primary anorectal melanoma.
AB  - Primary malignant melanoma of the anus and rectum is a rare and aggressive
      neoplasm that tends to invade locally and metastasize early in the course of the
      disease. It is often misdiagnosed as hemorrhoids or as one of the other benign
      anorectal conditions and is thus linked to an overall poor prognosis and a 5-year
      survival rate of less than 20%. Optimal treatment is still controversial, and
      current evidence does not show any preferential survival benefit from
      abdominoperineal resection over wide local excision. Chemotherapy or radiotherapy
      may be used for advanced disease. We report a 71-year-old female presenting with
      painful bowel movements and blood in stools. She was eventually found to have a
      mass arising from the anorectal junction with regional lymph node involvement.
      The patient underwent an abdominoperineal resection and is currently scheduled
      for chemotherapy. 

PMID- 24748867
TI  - Pancreatic cancer presenting as new-onset diabetes.
AB  - Pancreatic adenocarcinoma has an incidence rate nearly equal to the mortality
      rate and is the fourth leading cause of cancer-related death in the USA. This is
      largely due to late symptom onset and diagnosis. Evidence has emerged that new
      onset diabetes may be a symptom caused by occult pancreatic cancer. We report the
      case of a middle-aged African American female who presented with hyperglycemia
      and persistent scapular tenderness. She was subsequently diagnosed with new-onset
      diabetes and metastatic pancreatic cancer confirmed by liver biopsy. She did not
      have diabetes or pre-diabetes in the 6 months prior to presentation. The
      following report will serve to emphasize the role of new-onset diabetes in
      certain patients as a warning sign necessitating further investigation for
      pancreatic cancer. New-onset diabetes associated with specific risk factors may
      prompt for early testing, detection and treatment of pancreatic cancer. 

PMID- 24748868
TI  - Giant adrenal myelolipoma masquerading as heart failure.
AB  - Adrenal myelolipomas are rare benign tumors of the adrenal cortex composed of
      adipose and hematopoietic cells. They have been postulated to arise from repeated
      stimulation by stress, inflammation and ACTH oversecretion. Myelolipomas are
      usually detected incidentally on imaging and do not require any active
      intervention besides regular follow-up by imaging. However, myelolipomas may
      insidiously grow to large sizes and cause mass effects and hemorrhage. Timely
      diagnosis and surgical resection are curative and lifesaving. 

PMID- 24748869
TI  - Reduced-intensity allogeneic stem cell transplantation for co-emergence of
      chemotherapy-refractory follicular lymphoma and therapy-related myelodysplastic
      syndrome.
AB  - A 54-year-old male was diagnosed with follicular lymphoma in September 2003.
      Despite multiple chemotherapies, including autologous hematopoietic stem cell
      transplantation (HSCT) with high-dose chemotherapy, the disease eventually
      relapsed. Additionally, bone marrow analysis revealed the co-emergence of therapy
      related myelodysplastic syndrome (t-MDS) in February 2012. In March 2012, we
      performed related allogeneic HSCT for the treatment of both malignancies. This
      strategy was successful and the patient has remained free from both malignancies
      for 23 months. Allogeneic HSCT is a potent curative therapeutic option for both t
      MDS and refractory follicular lymphoma. 

PMID- 24748870
TI  - Acinic cell carcinoma of the salivary gland with metastatic spread to the
      pancreas.
AB  - Metastatic disease to the pancreas is rare among solid tumors and has not been
      well described for salivary cancers. We report a patient who developed an
      isolated metastatic lesion in the pancreas from acinic cell carcinoma of the
      salivary gland, presenting as acute pancreatitis. 

PMID- 24748871
TI  - Intracranial metastasis in a patient with hepatocellular carcinoma and gastric
      cancer.
AB  - A 76-year-old man was referred to our hospital with visual disturbance, weakness
      of the left upper and lower limbs, and gait disturbance. He had previously
      received transarterial chemoembolization for hepatocellular carcinoma (HCC) 3 and
      10 years ago. When he had received radiofrequency ablation for HCC recurrence 2
      years ago, total gastrectomy was also performed for his gastric cancer.
      Subsequently, sorafenib had been administrated for concomitant lung metastatic
      tumors. On admission, MRI revealed an intra-axial tumor with perifocal edema. The
      level of carcinoembryonic antigen, but not alpha-fetoprotein, markedly increased.
      The tumor was successfully removed by craniotomy and pathological examination
      revealed that it was composed of adenocarcinoma, which was consistent with the
      primary gastric cancer. After surgery, his neurological disturbances rapidly
      resolved. Additional gamma-knife treatment was also performed for another small
      brain metastasis detected after craniotomy. Subsequently, sorafenib
      administration was discontinued and S-1 was administered postoperatively.
      Successful treatment of intracranial metastasis of gastric cancer is important
      and meaningful, even in patients with multiple primary malignancies. 

PMID- 24748872
TI  - Kimura's Disease of the Orbit Successfully Treated with Radiotherapy Alone: A
      Case Report.
AB  - We performed radiotherapy in a 28-year-old patient with Kimura's disease of the
      orbit. Irradiation with 21.6 Gy was administered to the tumor bed with a single
      dose of 1.8 Gy in 5 weekly fractions delivered via a high-energy linear
      accelerator (6-MV X-ray). Complete remission of the tumor and improvements in the
      neurological findings were achieved. Neither tumor regrowth nor late
      complications were detected up to 84 months after radiotherapy. Radiotherapy is
      an effective treatment for Kimura's disease of the orbit. 

PMID- 24748873
TI  - Vitreous Amyloidosis as the Presenting Symptom of Familial Amyloid Polyneuropathy
      TTR Val30Met in a Portuguese Patient.
AB  - Familial amyloid polyneuropathy (FAP) is a group of disorders characterized by
      the extracellular deposition of amyloid substance in various tissues. The
      peripheral nervous system and the heart are the main target organs, but the eye
      may also be involved. We report a case of vitreous amyloidosis as the first
      manifestation of FAP in a 66-year-old Portuguese man without a family history. 

PMID- 24748874
TI  - Closely related phytoplankton species produce similar suites of dissolved organic
      matter.
AB  - Production of dissolved organic matter (DOM) by marine phytoplankton supplies the
      majority of organic substrate consumed by heterotrophic bacterioplankton in the
      sea. This production and subsequent consumption converts a vast quantity of
      carbon, nitrogen, and phosphorus between organic and inorganic forms, directly
      impacting global cycles of these biologically important elements. Details
      regarding the chemical composition of DOM produced by marine phytoplankton are
      sparse, and while often assumed, it is not currently known if phylogenetically
      distinct groups of marine phytoplankton release characteristic suites of DOM. To
      investigate the relationship between specific phytoplankton groups and the DOM
      they release, hydrophobic phytoplankton-derived dissolved organic matter (DOMP)
      from eight axenic strains was analyzed using high-performance liquid
      chromatography coupled to mass spectrometry (HPLC-MS). Identification of DOM
      features derived from Prochlorococcus, Synechococcus, Thalassiosira, and
      Phaeodactylum revealed DOMP to be complex and highly strain dependent.
      Connections between DOMP features and the phylogenetic relatedness of these
      strains were identified on multiple levels of phylogenetic distance, suggesting
      that marine phytoplankton produce DOM that in part reflects its phylogenetic
      origin. Chemical information regarding the size and polarity ranges of features
      from defined biological sources was also obtained. Our findings reveal DOMP
      composition to be partially conserved among related phytoplankton species, and
      implicate marine DOM as a potential factor influencing microbial diversity in the
      sea by acting as a link between autotrophic and heterotrophic microbial community
      structures. 

PMID- 24748875
TI  - Development and course of heart failure after a myocardial infarction in younger
      and older people.
AB  - BACKGROUND: Acute myocardial infarction (AMI) is a common cause of heart failure
      (HF), which can develop soon after AMI and may persist or resolve or develop
      late. HF after an MI is a major source of mortality. The cumulative incidence,
      prevalence and resolution of HF after MI in different age groups are poorly
      described. This study describes the natural history of HF after AMI according to
      age. METHODS: Patients with AMI during 1998 were identified from hospital
      records. HF was defined as treatment of symptoms and signs of HF with loop
      diuretics and was considered to have resolved if loop diuretic therapy could be
      stopped without recurrence of symptoms. Patients were categorised into those aged
      < 65 years, 65-75 years, and > 75 years. RESULTS: Of 896 patients, 311, 297 and
      288 were aged < 65, 65-75 and >75 years and of whom 24%, 57% and 82% had died
      respectively by December 2005. Of these deaths, 24 (8%), 68 (23%) and 107 (37%)
      occurred during the index admission, many associated with acute HF. A further 37
      (12%), 63 (21%) and 82 (29%) developed HF that persisted until discharge, of whom
      15, 44 and 62 subsequently died. After discharge, 53 (24%), 55 (40%) and 37 (47%)
      patients developed HF for the first time, of whom 26%, 62% and 76% subsequently
      died. Death was preceded by the development of HF in 35 (70%), 93 (91%) and 107
      (85%) in aged < 65 years, 65-75 years and >75 years, respectively. CONCLUSIONS:
      The risk of developing HF and of dying after an MI increases progressively with
      age. Regardless of age, most deaths after a MI are preceded by the development of
      HF.

PMID- 24748876
TI  - Procoagulant activity of circulating microparticles is associated with the
      presence of moderate calcified plaque burden detected by multislice computed
      tomography.
AB  - BACKGROUND: Circulating microparticles (MPs) have been reported to be associated
      with coronary artery disease (CAD). In this study, we explored the relationship
      between MPs procoagulant activity and characteristics of atherosclerotic plaque
      detected by 64-slice computed tomography angiography (CTA). METHODS: In 127
      consecutive patients with CAD but without acute coronary syndrome and who
      underwent 64-slice CTA, MPs procoagulant activity in plasma (by a thrombin
      generation test), soluble form of lectin-like oxidized low-density lipoprotein
      receptor-1 (sLOX-1) and N(epsilon)-(carboxymethyl) lysine (CML) circulating
      levels (by ELISA) were measured. A quantitative volumetric analysis of the lumen
      and plaque burden of the vessel wall (soft and calcific components), for the
      three major coronary vessels, was performed. The patients were classified in
      three groups according to the presence of calcium volume: non-calcified plaque
      (NCP) group (calcium volume (%) = 0), moderate calcified plaque (MCP) group (0 <
      calcium volume (%) < 1), and calcified plaque (CP) group (calcium volume (%) >=
      1). RESULTS: MPs procoagulant activity and CML levels were higher in MCP group
      than in CP or NCP group (P = 0.009 and P = 0.027, respectively). MPs procoagulant
      activity was positively associated with CML (r = 0.317, P < 0.0001) and sLOX-1
      levels (r = 0.216, P = 0.0025). CONCLUSIONS: MPs procoagulant activity was higher
      in the MCP patient group and correlated positively with sLOX-1 and CML levels,
      suggesting that it may characterize a state of blood vulnerability that may
      locally precipitate plaque instability and increase the risk of subsequent major
      cardiovascular events.

PMID- 24748877
TI  - Aging effects on QT interval: Implications for cardiac safety of antipsychotic
      drugs.
AB  - OBJECTIVES: To explore the effect of aging on cardiac toxicity specifically the
      interaction of age and antipsychotic drugs to alter the QT interval. METHODS: THE
      MEDLINE DATABASES WERE SEARCHED USING THE OVIDSP PLATFORMS WITH THE SEARCH
      STRATEGY: "QT interval" or "QT" and "age" or "aging". The entry criteria were:
      over 10,000 apparently healthy individuals with data on both sexes; QT interval
      corrected for heart rate (QTc) and an expression of its variance for multiple age
      decades extending into the older ages. RESULTS: QTc increased in duration with
      increasing age. Considering a modest one SD increment in QTc in the normal
      population, the addition of Chlorpromazine produced a QTc on average greater than
      450 ms for ages 70 years and older. Risperidone, that did not on average alter
      QTc, would be expected to produce a QTc of 450 ms in persons in their mid 70
      years under some circumstances. QTc prolongation > 500 ms with antipsychotic
      drugs is more likely for persons with QTc initially at the 99(th) percentile. It
      may occur with Haloperidol which does not on average alter QTc. CONCLUSIONS: The
      range of values for the QT interval in apparently normal older men or women, when
      combined with the range of expected QT interval changes induced by antipsychotic
      drugs, can readily be associated with prolonged QTc. Individuals with QTc at the
      99(th) percentile may have serious QTc prolongation with antipsychotic drugs even
      those that are not usually associated with QTc prolongation.

PMID- 24748878
TI  - Long term outcomes of saphaneous vein graft intervention in elderly patients with
      prior coronary artery bypass graft.
AB  - OBJECTIVES: To investigate the procedure characteristics and long term follow-up
      of percutaneous coronary intervention (PCI) for saphaneous vein graft (SVG)
      lesions in the elderly patients. METHODS: From December 2005 to December 2011, 84
      graft lesions were treated percutaneously. Seventeen were located at proximal
      anastomosis, 48 were located at SVG body, 19 were located at distal anastomosis.
      Primary endpoint was defined as major adverse cardiovascular events (MACE,
      composite of cardiac death, target vessel revascularization, acute myocardial
      infarction). RESULTS: The graft age was 6.7 +/- 4.0 years. Most anastomosis
      lesions (80.0%) presented within one year post coronary artery bypass grafting
      (CABG). Proximal anastomosis lesion had the lowest successful rate for PCI
      compared with graft body and distal anastomosis lesions (70.6% vs. 91.7%, 79.0%,
      P < 0.05). The distal embolic protection device was used in 19.1% of patients,
      most frequently used in body graft PCI (29.2%, P < 0.01). The diameter of the
      stent was smallest in distal anastomosis group (2.9 +/- 0.4 mm, P < 0.05). The
      highest post dilatation pressure was required in the proximal anastomosis (17.8
      +/- 2.7 atm, P < 0.05). The patients were followed up for 24.3 +/- 16.9 months.
      MACE occurred in 18.57% of patients. Incidence of MACE was highest among proximal
      anastomosis PCI (47.1% vs. body graft PCI 16.7%, distal anastomosis PCI 21.1%; P
      < 0.05). Old myocardial infarction was the predictive factor for the poor
      clinical outcomes (P = 0.04). CONCLUSIONS: PCI of SVG lesions is feasible with
      lower success rate. PCI of ostial graft anastomosis lesions had the lowest
      procedure success rate and highest MACE rate compared with graft body and distal
      anastomosis lesions. Old myocardial infarction was a predictive factor of poor
      outcomes.

PMID- 24748879
TI  - Association between serum homocysteine and arterial stiffness in elderly: a
      community-based study.
AB  - BACKGROUND: Arterial stiffness and homocysteine are both powerful predictors of
      cardiovascular disease, especially in older populations. Previous studies have
      investigated the association of homocysteine with arterial stiffness in human
      subjects, while the relationship between homocysteine and arterial stiffness in
      the elderly is still indefinite. The current study examined the association of
      homocysteine with arterial stiffness in Chinese community-based elderly persons.
      METHODS: We related serum levels of homocysteine to two measures of arterial
      stiffness (carotid-femoral pulse wave velocity (PWV) and carotid-radial PWV) in
      780 participants (46.3% men, mean age 71.9 years (ranging 65-96 years old)) from
      two communities of Beijing, China. Arterial stiffness was measured within two
      days of the time of biomarker measurement. RESULTS: In multiple-adjusted models,
      homocysteine levels were strongly associated with the carotid-femoral PWV
      (standardized beta = 0.13, P < 0.001), even after adjustment for classical risk
      factors of cardiovascular disease. The association is also stronger when the
      carotid-femoral PWV is elevated above normal, whereas no significant association
      with homocysteine was observed for carotid-radial PWV. CONCLUSIONS: In Chinese
      elderly persons, serum homocysteine levels are associated with alterations of
      aortic stiffness.

PMID- 24748880
TI  - Safety and efficacy of intravenous esmolol before prospective electrocardiogram
      triggered high-pitch spiral acquisition for computed tomography coronary
      angiography.
AB  - BACKGROUND: In order to acquire a high quality image with a low radiation dose,
      prospective electrocardiogram (ECG)-triggered computed tomography coronary
      angiography (CTCA) requires a stable heart rate (HR) < 65 beats/min. Esmolol has
      the advantage of reducing HR. The objective of this article is to assess the
      value of intravenous esmolol treatment before prospective ECG-triggered high
      pitch spiral acquisition for CTCA. METHODS: From March 2013 to June 2013, 313
      patients underwent prospective ECG-triggered CTCA. Two hundred and thirty two of
      them received esmolol before angiography. We retrospectively analyzed clinical
      characteristics, esmolol dose, radiation exposure dose, and the change in HR and
      blood pressure in these 232 patients. RESULTS: A total of 232 patients with a HR
      > 65 beats/min before CTCA examination received intravenous esmolol treatment
      (mean dose of 57.26 +/- 15.39 mg). The mean initial HR (HR1), slowest HR (HR2),
      and the HR 30 min after HR2 (HR3) were 75.06 +/- 5.59, 60.75 +/- 4.00, and 75.54
      +/- 5.96 beats/min, respectively (HR1 vs. HR2, P < 0.0001; HR1 vs. HR3, P =
      0.377). The mean time from esmolol administration to HR2 was 24.25 +/- 4.97 s and
      the mean effective radiation dose was 2.28 +/- 0.02 mSv. CONCLUSIONS: HR could be
      rapidly controlled at an optimum level with intravenous esmolol before
      prospective ECG-triggered high-pitch spiral acquisition for CTCA. Consequently,
      the patients received a very low radiation dose.

PMID- 24748881
TI  - Cutting-balloon angioplasty before drug-eluting stent implantation for the
      treatment of severely calcified coronary lesions.
AB  - BACKGROUND: Severely calcified coronary lesions respond poorly to balloon
      angioplasty, resulting in incomplete and asymmetrical stent expansion. Therefore,
      adequate plaque modification prior to drug-eluting stent (DES) implantation is
      the key for calcified lesion treatment. This study was to evaluate the safety and
      efficacy of cutting balloon angioplasty for severely calcified coronary lesions.
      METHODS: Ninety-two consecutive patients with severely calcified lesions (defined
      as calcium arc >= 180 degrees  calcium length ratio >= 0.5) treated with balloon
      dilatation before DES implantation were randomly divided into two groups based on
      the balloon type: 45 patients in the conventional balloon angioplasty (BA) group
      and 47 patients in the cutting balloon angioplasty (CB) group. Seven cases in BA
      group did not satisfactorily achieve dilatation and were transferred into the CB
      group. Intravascular ultrasound (IVUS) was performed before balloon dilatation
      and after stent implantation to obtain qualitative and quantitative lesion
      characteristics and evaluate the stent, including minimum lumen cross-sectional
      area (CSA), calcified arc and length, minimum stent CSA, stent apposition, stent
      symmetry, stent expansion, vessel dissection, and branch vessel jail. In
      hospital, 1-month, and 6-month major adverse cardiac events (MACE) were reported.
      RESULTS: There were no statistical differences in clinical characteristics
      between the two groups, including calcium arc (222.2 degrees  +/- 22.2 degrees 
      vs. 235.0 degrees  +/- 22.1 degrees , P = 0.570), calcium length ratio (0.67 +/-
      0.06 vs. 0.77 +/- 0.05, P = 0.130), and minimum lumen CSA before PCI (2.59 +/-
      0.08 mm(2) vs. 2.52 +/- 0.08 mm(2), P = 0.550). After stent implantation, the
      final minimum stent CSA (6.26 +/- 0.40 mm(2) vs. 5.03 +/- 0.33 mm(2); P = 0.031)
      and acute lumen gain (3.74 +/- 0.38 mm(2) vs. 2.44 +/- 0.29 mm(2), P = 0.015)
      were significantly larger in the CB group than that of the BA group. There were
      not statistically differences in stent expansion, stent symmetry, incomplete
      stent apposition, vessel dissection and branch vessel jail between two groups.
      The 30-day and 6-month MACE rates were also not different. CONCLUSIONS: Cutting
      balloon angioplasty before DES implantation in severely calcified lesions appears
      to be more efficacies including significantly larger final stent CSA and larger
      acute lumen gain, without increasing complications during operations and the MACE
      rate in 6-month.

PMID- 24748882
TI  - Brain natriuretic peptide is a potent vasodilator in aged human microcirculation
      and shows a blunted response in heart failure patients.
AB  - BACKGROUND: Brain natriuretic peptide (BNP) is normally present in low levels in
      the circulation, but it is elevated in parallel with the degree of congestion in
      heart failure subjects (CHF). BNP has natriuretic effects and is a potent
      vasodilator. It is suggested that BNP could be a therapeutic alternative in CHF.
      However, we postulated that the high levels of circulating BNP in CHF may
      downregulate the response of microvascular natriuretic receptors. This was tested
      by comparing 15 CHF patients (BNP > 3000 ng/L) with 10 matched, healthy controls.
      METHODS: Cutaneous microvascular blood flow in the forearm was measured by laser
      Doppler Flowmetry. Local heating (+44 degrees C, 10 min) was used to evoke a
      maximum local dilator response. RESULTS: Non-invasive iontophoretic
      administration of either BNP or acetylcholine (ACh), a known endothelium
      dependent dilator, elicited an increase in local flow. The nitric oxide synthase
      inhibitor, l-N-Arginine- methyl-ester (L-NAME), blocked the BNP response (in
      controls). Interestingly, responses to BNP in CHF patients were reduced to about
      one third of those seen in healthy controls (increase in flow: 251% in CHF vs.
      908% in controls; P < 0.001). In contrast, the vasodilator responses to ACh and
      to local heating were only somewhat attenuated in CHF patients. Thus, dilator
      capacity and nitric oxide signalling were not affected to the same extent as BNP
      mediated dilation, indicating a specific downregulation of the latter response.
      CONCLUSIONS: The findings show for the first time that microvascular responses to
      BNP are markedly reduced in CHF patients. This is consistent with the hypothesis
      of BNP receptor function is downregulated in CHF.

PMID- 24748883
TI  - Correlation between serum free fatty acids levels and Gensini score in elderly
      patients with coronary heart disease.
AB  - OBJECTIVES: To investigate the relationship between serum free fatty acids (FFAs)
      levels and the severity of coronary artery lesions in elderly patients with
      coronary heart disease (CAD). METHODS: A total of 172 elderly patients who
      underwent coronary angiography were divided into CAD group (n = 128) and non-CAD
      group (n = 44) according to the results of coronary angiography. Serum FFAs and
      lipid levels were measured and the Gensini score were calculated. RESULTS: No
      matter the differences between age, gender and the usage of statins or not, there
      was no statistical significance in FFAs levels (P > 0.05). In terms of the
      Gensini score, it was higher in patients aged 70-79 years than in patients 60-69
      years old [15.00 (5.00, 34.00) vs. 10.00 (2.00, 24.00), P < 0.05], higher in men
      than women [14.00 (4.00, 34.00) vs. 7.00 (2.50, 19.75), P < 0.05], and higher in
      patients on statins [13.50 (4.25, 33.50) vs. 6.50 (2.00, 18.00), P < 0.05]. The
      serum FFAs levels [449.50 (299.00, 624.75) mEq/L vs. 388.00 (258.50, 495.25)
      mEq/L, P < 0.05] and Gensini score [17.50 (8.00, 41.75) vs. 1.00 (0, 5.00), P <
      0.05] were higher in the CAD group than in the non-CAD group. In the CAD group,
      there was no statistical significance in FFAs levels among patients with
      different numbers of diseased coronary vessels (P > 0.05). Furthermore, the FFAs
      levels were positively correlated with the Gensini score (r = 0.394, P = 0.005).
      Regression analysis showed that the FFAs levels were related to the Gensini score
      independently after adjusting for the other risk factors. CONCLUSIONS: The serum
      FFAs levels were associated with the Gensini score in elderly patients with CAD.
      It might indicate FFAs as a biomarker predicting the severity of coronary artery
      lesions.

PMID- 24748884
TI  - Ciliotherapy: a novel intervention in polycystic kidney disease.
AB  - BACKGROUND: Ciliopathies are a group of diseases associated with abnormal
      structure or function of primary cilia. Ciliopathies include polycystic kidney
      disease (PKD), a pathology associated with vascular hypertension. We previously
      showed that cilia length regulates cilia function, and cilia function is required
      for nitric oxide (NO) biosynthesis in endothelial cells. Because patients with
      PKD show abnormal sensory cilia function, the aim of our current study was to
      search for a targeted therapy focused on primary cilia, which we refer to as
      'ciliotherapy'. METHODS AND RESULTS: In the present studies, our in vitro
      analyses refined fenoldopam as an equipotent and more specific dopaminergic
      agonist to regulate cilia length and function. Our in vivo studies indicated that
      fenoldopam increased cilia length and serum NO thereby reducing blood pressure in
      a PKD mouse model. Our crossover, multicenter, double-blind and placebo
      controlled clinical study further indicated that cilia-targeting therapy showed
      an overall reduction in mean arterial pressure in PKD patients. CONCLUSIONS:
      Overall, our studies provide the first evidence of ciliotherapy as an innovative
      intervention in patients with abnormal primary cilia.

PMID- 24748885
TI  - Hyperhomocysteinemia independently causes and promotes atherosclerosis in LDL
      receptor-deficient mice.
AB  - BACKGROUND: Hyperhomocysteine is an independent risk factor of coronary heart
      disease (CHD). However, whether hyperhomocysteine affects the progression of
      atherosclerosis is unclear. In the present study, we examined the effect of
      hyperhomocysteine on the formation of atherosclerosis in low-density lipoprotein
      receptor-deficient (LDLr(-/-)) mice. METHODS: Forty-eight 7-week-old LDLr(-/-)
      mice were assigned to the following groups: mice fed a standard rodent diet
      (control group), mice fed a high-methionine diet (high-methionine group), mice
      fed a high-fat diet (high-fat group), and mice fed a diet high in both methionine
      and fat (high-methionine and high-fat group). At the age of 19, 23, and 27 weeks,
      four mice at each interval in every group were sacrificed. RESULTS: At the end of
      the study, mice did not show atherosclerotic lesions in the aortic sinus and
      aortic surface until 27 weeks old in the control group. However, atherosclerotic
      lesions developed in the other three groups at 19 weeks. The amount of
      atherosclerotic lesions on the aortic surface was lower in the high-methionine
      group than in the high-fat group (P < 0.001). Atherosclerotic lesions on the
      aortic surface in the high-methionine and high-fat group were the most severe.
      The mean area of atherosclerotic lesions in the aortic sinus compared with
      atherosclerotic lesions on the aortic surface was lower in the high-methionine
      group than in the high-fat group (P < 0.001). Atherosclerotic lesions in the
      aortic sinus in the high-methionine and high-fat group were the most severe.
      CONCLUSIONS: Homocysteinemia accelerates atherosclerotic lesions and induces
      early atherosclerosis independently in LDLr(-/-) mice. Reducing the level of
      homocysteinemia may be beneficial for prevention and treatment of CHD.

PMID- 24748886
TI  - Comparative study of galectin-3 and B-type natriuretic peptide as biomarkers for
      the diagnosis of heart failure.
AB  - BACKGROUND: Heart failure (HF) is a common disease with complex
      pathophysiological causes. The diagnosis of HF commonly relies on comprehensive
      analyses of medical history and symptoms, and results from echocardiography and
      biochemical tests. Galectin-3, a relatively new biomarker in HF, was approved by
      the US Food and Drug Administration in 2010 as a marker in the stratification of
      risk for HF. We assessed galectin-3 as a biomarker for HF diagnosis in patients
      with preserved ejection fraction (pEF) and compared its performance with that of
      B-type natriuretic peptide (BNP). METHODS: Thirty-five pEF patients with HF
      (HFpEF group) and 43 pEF patients without HF (control group) were enrolled.
      Plasma levels of galectin-3 and BNP in HFpEF and control subjects were
      determined. Sensitivity, specificity, predictive values, and accuracy of galectin
      3 and BNP as markers for HF diagnosis were calculated and compared. RESULTS:
      Levels of galectin-3 and BNP were 23.09 +/- 6.97 ng/mL and 270.46 +/- 330.41
      pg/mL in the HFpEF group, and 16.74 +/- 2.75 ng/mL and 59.94 +/- 29.93 pg/mL in
      the control group, respectively. Differences in levels of galectin-3 and BNP
      between the two groups were significant (P < 0.01). As a biomarker for HF
      diagnosis in study subjects, galectin-3 showed sensitivity and specificity of
      94.3% and 65.1%, respectively, at a cutoff value of 17.8 ng/mL. BNP showed
      sensitivity and specificity of 77.1% and 90.7%, respectively, at a cutoff value
      of 100 pg/mL. Galectin-3 was a significantly more sensitive (P < 0.05) but less
      specific (P < 0.01) biomarker compared with BNP. Differences in positive
      predictive value, negative predictive value, and accuracy between galectin-3 and
      BNP markers were not significant (P > 0.05). Areas under the receiver operating
      characteristic curve (95% confidence interval) were 0.891 (0.808-0.974) and 0.896
      (0.809-0.984) for galectin-3 and BNP, respectively, with no significant
      difference between the two values (P > 0.05). CONCLUSIONS: The level of galectin
      3 is significantly elevated in patients with HF. Galectin-3 and BNP are useful
      biomarkers for the diagnosis of HF in patients with pEF.

PMID- 24748887
TI  - Is the advantage of coronary bypass graft surgery over percutaneous coronary
      intervention in diabetic patients with severe multivessel disease influenced by
      the status of insulin requirement?
AB  - Several studies have shown that coronary artery bypass graft surgery (CABG) is
      superior to percutaneous coronary intervention (PCI) in patients with diabetes
      and multi-vessel disease. Whether this advantage of CABG over PCI is confined to
      diabetics who require insulin is unknown. We review the published literature
      comparing CABG with PCI in diabetics including 8 cohorts and 4,786 patients.
      There was a lower rate for all-cause mortality (Relative risk (RR): 0.78, 95%
      confidence interval (CI): 0.62-0.99), and for major adverse cardiac and
      cerebrovascular events (MACCE, RR: 0.59, 95% CI: 0.47-0.75) for CABG compared to
      PCI. Composite outcome of mortality, myocardial infarction and stoke was similar
      between CABG and PCI (RR: 0.87, 95% CI: 0.54-1.42). Visual inspection of the
      forest plots showed that in most analyses, the point estimates of the RR are
      similar between the insulin requiring group and non-insulin requiring group. On
      meta-regression, there was no interaction between status of insulin requirement
      and revascularization strategies (P > 0.05 for all). The presented data on the
      still unpublished analysis of the FREEDOM trial showed similar results. Thus, in
      the current era, CABG is superior to PCI with lower mortality and MACCE rates,
      but the state of insulin requirement had no effect on the outcomes from the two
      revascularization strategies. 

PMID- 24748888
TI  - Novel treatment of coronary artery fistulae concealing severe coronary artery
      lesion: using thrombus aspiration catheter as a delivery guide.
AB  - In this case report, we present the occlusion of multiple coronary artery
      fistulae originating from proximal left anterior descending (LAD) and right sinus
      valsavla and empting to the pulmonary artery at the same place. We occluded LAD
      fistulae by using thrombus aspiration catheter as a delivery guide. To the best
      of our knowlege, this is the first case of occlusion of coronary fistulae with
      the help of thrombus aspiration catheter. Our experience may suggest that
      thrombus aspiration catheters can be used in treating coronary artery fistulae
      with difficult anotomy. 

PMID- 24748889
TI  - Methods for Analyzing Multivariate Phenotypes in Genetic Association Studies.
AB  - This is an open access article distributed under the Creative Commons Attribution
      License, which permits unrestricted use, distribution, and reproduction in any
      medium, provided the original work is properly cited. Multivariate phenotypes are
      frequently encountered in genetic association studies. The purpose of analyzing
      multivariate phenotypes usually includes discovery of novel genetic variants of
      pleiotropy effects, that is, affecting multiple phenotypes, and the ultimate goal
      of uncovering the underlying genetic mechanism. In recent years, there have been
      new method development and application of existing statistical methods to such
      phenotypes. In this paper, we provide a review of the available methods for
      analyzing association between a single marker and a multivariate phenotype
      consisting of the same type of components (e.g., all continuous or all
      categorical) or different types of components (e.g., some are continuous and
      others are categorical). We also reviewed causal inference methods designed to
      test whether the detected association with the multivariate phenotype is truly
      pleiotropy or the genetic marker exerts its effects on some phenotypes through
      affecting the others.

PMID- 24748890
TI  - Prevalence of obesity in patients with type 2 diabetes mellitus in yemen.
AB  - BACKGROUND: Obesity is common in type 2 diabetic patients in some of the Middle
      Eastern countries, which are amongst the countries with highest rates of diabetes
      mellitus and obesity. OBJECTIVES: We conducted this study to assess the
      prevalence of obesity in Yemeni patients with type 2 diabetes mellitus. PATIENTS
      AND METHODS: Body mass index (BMI) of patients with type 2 diabetes mellitus who
      were 25-years-old or older was measured during their first visit to an
      endocrinology and diabetes clinic in Sana'a, Yemen over a 4-year period from May
      2007 to May 2011. RESULTS: The BMI was measured in 1640 patients (721 males and
      919 females) who attended the clinic. According to the measured BMI, 328 (45.5%),
      314 (43.5%), 79 (11%) of the male patients were non-obese (BMI < 25 kg/m(2)),
      overweight (BMI 25-29.9 kg/m(2)), and obese (BMI >= 30 kg/m(2)), respectively. On
      the other hand, 256 (28%), 369 (40.0%), and 294 (32%) of the female patients were
      non-obese (BMI < 25 kg/m(2)), overweight (BMI 25-29.9 kg/m(2)), and obese (BMI >=
      30 kg/m(2)), respectively. CONCLUSIONS: The prevalence of obesity in patients
      with type 2 diabetes mellitus in Yemen is high with respect to the Yemeni
      population, especially in females.

PMID- 24748891
TI  - Serial explantation after parathyroid autotransplant for recurrent hypercalcemia
      in chronic renal failure.
AB  - INTRODUCTION: Development of autonomous parathyroid gland function can occur in
      cases of long standing renal disease, leading to hyperparathyroidism and
      hypercalcemia. Debate exists over the optimum surgical treatment strategy and the
      choice lies with the individual surgeon. We illustrated the method of total
      parathyroidectomy and autotransplantation to the forearm and proposed it to be
      superior to both total and subtotal parathyroidectomy. CASE PRESENTATION: This
      case illustrated the development of secondary and subsequently tertiary
      hyperparathyroidism in a 66-year-old man with a history of chronic renal failure.
      The patient was managed surgically by parathyroid autotransplantation and serial
      explantation. DISCUSSION: Refractory hypercalcemia due to autonomous parathyroid
      tissue following parathyroidectomy can be managed with greater ease and efficacy
      by serial explantation of autotransplanted tissue versus a more difficult re
      exploration of the neck.

PMID- 24748892
TI  - Lack of Association Between Transforming Growth Factor Beta 1 -509C/T and +915G/C
      Polymorphisms and Chronic Hepatitis B in Iranian Patients.
AB  - BACKGROUND: Chronic hepatitis B is one of the world's major health concerns
      [corrected]. The etiological agent of this infection is hepatitis B virus (HBV),
      which can evade the immune system response. Transforming growth factor beta 1
      (TGF-beta1) can act against HBV by suppressing the viral replication. The TGF
      beta1 also plays an important role in preventing liver damage in chronically HBV
      infected patients. OBJECTIVES: In this study, the association of TGF-beta1
      +915G/C and -509C/T gene polymorphisms with chronic hepatitis B was evaluated in
      Iranian patients. MATERIALS AND METHODS: A population-based case-control study
      was conducted in Taleghani Hospital, Tehran. A number of 220 patients with
      chronic hepatitis B and the same number of healthy control subjects were
      designated the case and the control groups. The PCR-Restriction Fragment Length
      Polymorphism Method (PCR-RFLP) method was used for genotyping both polymorphisms.
      Ten percent of the control samples were sequenced to confirm the results.
      RESULTS: No statically significant differences in genotype distribution and
      allele frequency were observed for both polymorphisms between healthy controls
      and patients with chronic hepatitis B. CONCLUSIONS: There was no association
      between TGF-beta1 -509C/T and +915G/C polymorphisms with chronic hepatitis B and
      it seems that these changes do not play a significant role in increasing the risk
      of chronic infection in Iranian patients [corrected].

PMID- 24748893
TI  - Alanine aminotransferase elevation in obese infants and children: a marker of
      early onset non alcoholic Fatty liver disease.
AB  - BACKGROUND: Elevated aminotransferases serve as surrogate markers of non
      alcoholic fatty liver disease, a feature commonly associated with the metabolic
      syndrome. Studies on the prevalence of fatty liver disease in obese children
      comprise small patient samples or focus on those patients with liver enzyme
      elevation. OBJECTIVES: We have prospectively analyzed liver enzymes in all
      overweight and obese children coming to our tertiary care centre. PATIENTS AND
      METHODS: In a prospective study 224 healthy, overweight or obese children aged 1 
      12 years were examined. Body Mass Index-Standard Deviation Score, alanine
      aminotransferase, aspartate aminotransferase and gamma-glutamyl-transpeptidase
      were measured. RESULTS: Elevated alanine aminotransferase was observed in 29% of
      children. 26 % of obese and 30 % of overweight children had liver enzyme
      elevations. Obese children had significantly higher alanine aminotransferase
      levels than overweight children (0.9 vs. 0.7 times the Upper Limit of Normal; P =
      0.04). CONCLUSIONS: Elevation of liver enzymes appears in 29 % obese children in
      a tertiary care centre. Absolute alanine aminotransferase levels are
      significantly higher in obese than in overweight children. Even obese children
      with normal liver enzymes show signs of fatty liver disease as demonstrated by
      liver enzymes at the upper limit of normal.

PMID- 24748894
TI  - Pulse oximeter oxygen saturation in prediction of arterial oxygen saturation in
      liver transplant candidates.
AB  - BACKGROUND: Liver transplant is the only definitive treatment for many patients
      with end stage liver disease. Presence and severity of preoperative pulmonary
      disease directly affect the rate of postoperative complications of the liver
      transplantation. Arterial blood gas (ABG) measurement, performed in many
      transplant centers, is considered as a traditional method to diagnose hypoxemia.
      Because ABG measurement is invasive and painful, pulse oximetry, a bedside,
      noninvasive and inexpensive technique, has been recommended as an alternative
      source for the ABG measurement. OBJECTIVES: The aim of this study was to evaluate
      the efficacy of pulse oximetry as a screening tool in hypoxemia detection in
      liver transplant candidates and to compare the results with ABGs. PATIENTS AND
      METHODS: Three hundred and ninety transplant candidates (237 males and 153
      females) participated in this study. Arterial blood gas oxyhemoglobin saturation
      (SaO2) was recorded and compared with pulse oximetry oxyhemoglobin saturation
      (SpO2) results for each participants. The area under the curve (AUC) of receiver
      operating characteristic (ROC) curves was calculated by means of nonparametric
      methods to evaluate the efficacy of pulse oximetry to detect hypoxemia. RESULTS:
      Roc-derived SpO2 threshold of <= 94% can predict hypoxemia (PaO2 < 60 mmHg) with
      a sensitivity of 100% and a specificity of 95%. Furthermore, there are
      associations between the ROC-derived SpO2 threshold of <= 97% and detection of
      hypoxemia (PaO2 < 70 mmHg) with a sensitivity of 100% and a specificity of 46%.
      The accuracy of pulse oximetry was not affected by the severity of liver disease
      in detection of hypoxemia. CONCLUSIONS: Provided that SpO2 is equal to or greater
      than 94%, attained from pulse oximetry can be used as a reliable and accurate
      substitute for the ABG measurements to evaluate hypoxemia in patients with end
      stage liver disease.

PMID- 24748896
TI  - Distinct Toll-like Receptor 3 and 7 Expression in Peripheral Blood Mononuclear
      Cells From Patients with Chronic Hepatitis C Infection.
AB  - BACKGROUND: Hepatitis C virus (HCV) is a major cause of chronic liver disease,
      with around 130 million infected people worldwide. HCV is recognized by Toll-like
      receptors (TLRs), which are key mediators of innate immune response. Up on
      activation of TLRs, anti-viral cytokines and pre-inflammatory are produced.
      OBJECTIVES: In this study, we compared the expression levels of two members of
      the TLR family (TLR3 and TLR7) that recognize viral RNA in peripheral blood
      mononuclear cell (PBMC) of patients with chronic HCV infection and healthy
      controls. PATIENTS AND METHODS: In this case-control study, blood samples were
      collected from patients admitted to Blood Transfusion Research Center, Tehran,
      Iran. PBMC was isolated from blood of chronic HCV patients (n = 25) and age and
      sex-matched healthy controls (n = 25). RNA was extracted from PBMC and cDNA was
      synthesized from total RNA templates using reverse transcriptase. The relative
      level of expression was quantified by real-time PCR using Glyceraldehyde-3
      phosphate dehydrogenase (GAPDH) as reference gene and the results were compared
      by Pfaffl method. Data were analyzed using non-parametric Wilcoxon test. P < 0.05
      was considered significant. RESULTS: In both groups, we had 13 males and 12
      females with a mean age of 48.7 +/- 16. TLR3 (6.23 +/- 0.91 vs. 3.89 +/- 0.85, P
      < 0.001) and TLR7 (1.48 +/- 0.82 vs-1.33 +/- 1.18, P < 0.001) expressions were
      significantly lower in patients with chronic HCV infection when compared with
      healthy controls. CONCLUSIONS: This study suggests that decrease in levels of
      TLR3 and TLR7 expression is a mechanism that may enable HCV to evade the host
      innate immune response.

PMID- 24748895
TI  - Association of Proton Pump Inhibitor Therapy with Hepatic Encephalopathy in
      Hepatitis B Virus-related Acute-on-Chronic Liver Failure.
AB  - BACKGROUND: Hepatic encephalopathy (HE) is an important neuropsychiatry
      complication of acute-on-chronic liver failure (ACLF). PPI therapy may increase
      the intestinal bacterial overgrowth and infections. OBJECTIVES: The aim of this
      study was to assess whether PPI use in ACLF is associated with HE. PATIENTS AND
      METHODS: A retrospective case-control study was performed. Fifty five admitted
      patients with hepatitis B virus (HBV)-related ACLF complicated by Stage II-IV HE
      developed after admission between January 2008 and December 2012 were matched (by
      sex, age, and MELD score) with comparable HBV-related ACLF patients (n = 110) who
      did not develop this complication during hospitalization. We excluded combined HE
      upon admission and other neurological disorders in patients with ACLF. Univariate
      and multivariate analyses of 30 variables (laboratory examination,
      predisposition, treatment, etc.) before the occurrence of HE were carried out to
      identify the factors predictive of HE. RESULTS: In univariate analysis, patients
      with HE in ACLF had a significantly higher rate of PPI use (89.1%) compared with
      non-HE (63.6%, P = 0.001). In addition, clinical and standard laboratory
      variables were significantly different between the two groups regarding the
      infection rate, hyponatremia, alpha-fetoprotein (AFP), Arginine Hydrochloride use
      and Lactulose use. Logistic regression analysis was used to examine the combined
      effects of the variables with HE as the outcome. HE in ACLF was associated with
      hyponatremia (odds ratio (OR) = 6. 318, 95% confidence interval (CI) = 2. 803
      14.241; P = 0. 000), PPI use was independently associated with HE (OR = 4. 392,
      CI = 1. 604-12.031; P = 0. 004), and lactulose use was protective (OR = 0. 294,
      CI = 0. 136-0.675; P = 0. 003). CONCLUSIONS: The occurrence of HE is associated
      with hyponatremia and PPI use in patients with ACLF.

PMID- 24748897
TI  - Evaluation of the relation between hepatic fibrosis and basic laboratory
      parameters in patients with chronic hepatitis B fibrosis and basic laboratory
      parameters.
AB  - BACKGROUND: The hepatitis B virus is an important healthcare problem. According
      to current clinical practice, a liver biopsy is required for the diagnosis and
      treatment of chronic liver disease. However, a liver biopsy is an invasive,
      inconvenient procedure, which requires an expert pathologist opinion. Therefore
      requirement of biochemical tests, which are considered to indicate hepatic
      fibrosis and may be repeated easily, increases gradually today. OBJECTIVES: This
      study evaluated the correlation between hepatic fibrosis and routine laboratory
      values in patients with chronic hepatitis B. PATIENTS AND METHODS: The files of
      456 patients with CHB (chronic hepatitis B) who were referred to the infectious
      diseases and clinical microbiology clinic between January 2009 and March 2012
      were screened retrospectively. Liver biopsy samples were examined according to
      Ishak scoring. Laboratory parameters and histopathology reports were recorded,
      and correlations between the fibrosis grade and laboratory parameters were
      analyzed. RESULTS: There were 320 male and 136 female patients, with a mean age
      36.7 +/- 12.1 years. According to liver biopsy results, a low fibrosis score
      (stage 0-2) was detected in 281 patients (61.6%), and a high fibrosis score
      (stage 3-5) was detected in 175 patients (38.4%). Patients with a high fibrosis
      score had significantly higher ALT (alanine amino transferase), AST (aspartate
      aminotransferase), and HBV-DNA values and a significantly lower platelet count
      compared with those with a low fibrosis score (P = 0.001, 0.001, 0.025, and
      0.001, respectively). A positive correlation was detected between the fibrosis
      score and age, BMI, HAI, ALT, and AST values, and a negative correlation was
      detected between the fibrosis score and albumin and platelet counts. In the
      regression analysis performed to evaluate the factors associated with high-stage
      fibrosis, fibrosis was determined to be associated with thrombosis, ALT, and
      gender. The results of the regression analysis demonstrated that the risk of
      fibrosis was 4.6 fold higher in men. CONCLUSIONS: According to the results
      obtained in our study, advanced age, higher BMI, AST, ALT, and HBV-DNA levels,
      and low albumin and platelet levels are correlated with advanced fibrosis in
      patients with CHB.

PMID- 24748898
TI  - Survivor mission: Do those who survive have a drive to thrive at work?
AB  - Are helping professionals who have experienced the same types of struggles as
      their clients more engaged at work? In the current investigation, we examine this
      question in samples of police detectives (with and without a history of violent
      victimization) and mental health workers (with and without a history of mental
      illness). Our results indicate that police detectives who have experienced
      violent victimization and mental health professionals who have experienced the
      same mental illness as their clients do indeed exhibit greater work engagement
      than their colleagues who lack these parallel life experiences. The link between
      a professional's firsthand experience of his/her client's hardships and work
      engagement appears to be partially explained by higher levels of grit among
      police detectives and by a greater sense of life-narrative continuity among
      mental health professionals.

PMID- 24748899
TI  - Internal State Language in the Storybook Narratives of Children with and without
      Autism Spectrum Disorder: Investigating Relations to Theory of Mind Abilities.
AB  - The current study examines narratives elicited using a wordless picture book,
      focusing on language used to describe the characters' thoughts and emotions
      (i.e., internal state language, ISL). The sample includes 21 children with Autism
      Spectrum Disorder (ASD) and 24 typically developing controls, matched on
      children's gender, IQ, as well as receptive and expressive vocabulary. This
      research had three major findings. First, despite equivalent performance on
      standardized language assessments, the volume of children's narratives (i.e., the
      number of utterances and words, the range of unique verbs and adjectives) was
      lower in children with ASD than in typically developing controls. Second, after
      controlling for narrative volume, the narratives of children with ASD were less
      likely to reference the characters' emotions than was the case for typically
      developing controls. Finally, our results revealed a specific association between
      children's use of emotion terms and their performance on a battery of
      experimental tasks evaluating children's Theory of Mind abilities. Implications
      for our understanding of narrative deficits in ASD as well as interventions that
      use narrative as a context for improving social comprehension are discussed.

PMID- 24748901
TI  - Potential Mechanisms of Action in the Treatment of Social Impairment and
      Disorganization in Adolescents with ADHD.
AB  - Two important domains that can be impaired in adolescents with ADHD are
      organization and social functioning; however, the development of interventions to
      target these areas in adolescents is in the early stages. Currently, small
      efficacy trials are beginning to be used to conduct preliminary tests on the
      proposed mechanisms of action for these interventions. These two studies examined
      the efficacy of organization and social functioning interventions for adolescents
      with ADHD, as well as the potential mechanisms of action for each intervention.
      Results from the organization intervention provide support for a significant
      relationship between performance on the organization checklist and overall GPA;
      however, there was no meaningful pattern of relationships between achieving
      mastery of the organization tasks and grades within quarter. Further, results
      from the social functioning intervention support a moderate relationship between
      performance on process measures of response to the intervention and outcome
      measures of social functioning. Results of this study provide implications for
      modifications to the measures and intervention procedures in future research.

PMID- 24748900
TI  - Microencapsulation of Lactobacillus acidophilus NCIMB 701748 in matrices
      containing soluble fibre by spray drying: Technological characterization, storage
      stability and survival after in vitro digestion.
AB  - We evaluated sodium alginate, chitosan and hydroxypropyl methylcellulose (HPMC)
      as co-encapsulants for spray dried Lactobacillus acidophilus NCIMB 701748 by
      assessing their impact on cell viability and physicochemical properties of the
      dried powders, viability over 35 days of storage at 25  degrees C and survival
      after simulated digestion. Fibres were added to a control carrier medium
      containing whey protein concentrate, d-glucose and maltodextrin. Sodium alginate
      and HPMC did not affect cell viability but chitosan reduced viable counts in
      spray dried powders, as compared to the control. Although chitosan caused large
      losses of viability during spray-drying, these losses were counteracted by the
      excellent storage stability compared to control, sodium alginate and HPMC, and
      the overall effect became positive after the 35-day storage. Chitosan also
      improved survival rates in simulated GI conditions, however no single fibre could
      improve L. acidophilus NCIMB 701748 viability in all steps from production
      through storage and digestion.

PMID- 24748902
TI  - Scalable and fault tolerant orthogonalization based on randomized distributed
      data aggregation.
AB  - The construction of distributed algorithms for matrix computations built on top
      of distributed data aggregation algorithms with randomized communication
      schedules is investigated. For this purpose, a new aggregation algorithm for
      summing or averaging distributed values, the push-flow algorithm, is developed,
      which achieves superior resilience properties with respect to failures compared
      to existing aggregation methods. It is illustrated that on a hypercube topology
      it asymptotically requires the same number of iterations as the optimal all-to
      all reduction operation and that it scales well with the number of nodes.
      Orthogonalization is studied as a prototypical matrix computation task. A new
      fault tolerant distributed orthogonalization method rdmGS, which can produce
      accurate results even in the presence of node failures, is built on top of
      distributed data aggregation algorithms.

PMID- 24748903
TI  - Modern non-invasive diagnostic techniques in the detection of early cutaneous
      melanoma.
AB  - Over the past few years melanoma has grown into a disease of socio-economic
      importance due to the increasing incidence and persistently high mortality rates.
      Melanoma is a malignant tumor with a high tendency to metastasize. Therefore, an
      extremely important part of the therapeutic process is to identify the disease at
      an early stage: in situ or stage I. Many tools for early diagnosis of melanoma
      are available today, including dermoscopy, videodermoscopy and in vivo
      reflectance confocal microscopy. Other methods such as high frequency ultrasound,
      optical coherence tomography and electrical impedance spectroscopy may serve as
      additional diagnostic aids. Modern imaging techniques also allow the monitoring
      of melanocytic skin lesions over months or years to detect the moment of
      malignant transformation. This review summarizes the current knowledge about
      modern diagnostic techniques, which may aid early diagnosis of melanoma. 

PMID- 24748904
TI  - Mucous membranepemphigoid in two half-sisters. The potential roles of
      autoantibodies to beta4 integrin subunits and HLA-DQbeta1*0301.
AB  - BACKGROUND: Mucous membrane pemphigoid (MMP) is a subepithelial autoimmune
      mucocutaneous disease. It most frequently affects the oral mucosa, followed by
      ocular and nasal mucosa, nasopharyngeal, anogenital, skin, laryngeal and
      esophageal mucosa. MAIN OBSERVATION: Two half-sisters developed mucous membrane
      pemphigoid at approximately the same age. The older sister presented with
      primarily mucosal disease, while the younger had a more cutaneous disease. The
      histopathology demonstrated a subepithelial blister and direct immunofluorescence
      showed deposition of IgG and C3 at the basement membrane zone of perilesional
      tissues in both sisters. Antibodies to human beta4 integrin were present in the
      sera of both patients and correlated with disease activity. Both sisters carried
      the same HLADQbeta1* 0301 allele. CONCLUSIONS: This is the first case of mucous
      membrane pemphigoid occurring in two half-sisters. Perhaps, it is the low
      incidence of mucous membrane pemphigoid that may account for the lack of reports
      on familial cases of the disease.

PMID- 24748905
TI  - Oleomas mimicking cutaneous xanthomas following breast augmentation by injection
      of liquid silicone.
AB  - BACKGROUND: Oleoma is defined as a foreign body granuloma resulting from the
      injection of oily substances into the skin or subcutaneous tissue. Liquid
      injectable silicone has been used extensively over the last five decades for soft
      tissue augmentation. Although initially considered as a biologically inert
      material, it has been implicated in a variety of adverse reactions, sometimes
      with latent periods of decades. MAIN OBSERVATIONS: We describe the case of a 44
      year-old Peruvian woman presenting with multiple painless yellowish papules and
      plaques limited to the lower half of the breasts, that seemed to be cutaneous
      xanthomas. A skin biopsy showed granulomatous inflammation with multiple clear
      vacuoles corresponding to injected liquid silicone particles, diagnosed as
      oleoma. The patient was then re-evaluated and she reported that she underwent
      breast augmentation by injection of liquid silicone five prior to presentation in
      our department. Thus, the diagnosis of oleoma was confirmed. CONCLUSIONS: We
      describe a case with yellowish papules on both breasts in a woman that underwent
      breast augmentation by injection of liquid silicone. Since this unusual
      presentation of oleomas can be confused with cutaneous xanthomas, a biopsy is
      essential for diagnosis.

PMID- 24748906
TI  - Clinical response of acneiform eruptions caused by cetuximab to administration of
      oral tetracycline and topical ketoconazole.
AB  - BACKGROUND: Cutaneous adverse events associated with the use of epidermal growth
      factor receptor inhibitors, such as cetuximab are relatively common. Although
      there are reports about possible treatments for acne or acneiform lesions induced
      by cetuximab, there are only few reports of prospective studies. OBJECTIVE: The
      aim of the study was to analyze the efficacy of varius treatment modalities and
      their combinations in patients with acneiform eruptions caused by cetuximab.
      PATIENTS AND METHODS: We studied 14 patients treated with an epidermal growth
      factor receptor inhibitors, including 7 patients cetuximab, who developed
      acneiform eruptions in the course of therapy. All patients were diagnosed as
      grade II according to the Common Terminology Criteria for Adverse Events (CTCAE)
      v4.0. A corticosteroid ointment, tacrolimus ointment, and ketoconazole ointment
      were used in a randomized manner. Oral therapy included administration of
      antihistaminic drugs, tetracycline, a cyclooxygenase inhibitor, or a macrolide.
      We measured the numer of days required to achieve improvement from grade II to
      grade I during cetuximab treatment. RESULTS: Our results showed that tetracycline
      treatment may shorten the period needed to achieve improvement. Ketoconazole
      cream and a combination of oral tetracycline and topical ketoconazole also
      significantly shortened this period. CONCLUSION: The results of our short case
      study may indicate that a combitation therapy of oral tetracyclin and topical
      ketokonazole is most effective in the therapy of patients with acneiform
      eruptions caused by cetuximab.

PMID- 24748907
TI  - Wound management with compression therapy and topical hemoglobin solution in a
      patient with Budd-Chiari Syndrome.
AB  - BACKGROUND: Although the underlying primary cause of chronic wounds may vary, a
      common etiology of this is a hypoxic or ischemic status of the affected tissue of
      the lower extremities. In particular, for rare diseases associated with disturbed
      blood flow a correlation between cause and effect is often diagnosed
      inappropriately. As a consequence, chronic wounds may develop and persist for
      years. MAIN OBSERVATIONS: We present a case of a patient with chronic venous
      insufficiency due to an occlusion of the inferior caval vein. Initially, a Budd
      Chiari syndrome was diagnosed which is a thrombotic obstruction of the hepatic
      venous outflow. In addition, the patient developed an obstruction of the inferior
      caval vein and subsequently a chronic venous insufficiency. As a consequence,
      chronic leg ulcers developed with a history of more than 7 years. Various wound
      care approaches were performed without success in wound closure. Finally, a
      combination of compression therapy and topical application of a hemoglobin
      solution successfully led to fast and persistent wound closure. CONCLUSIONS:
      Chronic ulcers of the lower limb such as venous leg ulcers, even for patients
      with rare disorders like Budd-Chiari syndrome, are associated with oxygen supply
      disturbances resulting in a hypoxic status of the affected tissue. Therefore, an
      adequate oxygen supply to chronic wounds plays a pivotal role in successful wound
      healing. Compression therapy in combination with enhancement of the local oxygen
      supply by topically applied hemoglobin showed marked improvement of wound healing
      in the presented patient.

PMID- 24748908
TI  - Bullous pemphigoid associated with dipeptidyl peptidase IV inhibitors. A case
      report and review of literature.
AB  - BACKGROUND: Bullous pemphigoid is a cutaneous autoimmune blistering disorder. The
      etiology for what precipitates this disease is not entirely clear at this point,
      although it has been associated with certain medications. MAIN OBSERVATION: We
      describe the case of a 70-year-old male with a past medical history of diabetes
      type 2 who developed a diffuse eruption of bullae with skin biopsy positive for
      bullous pemphigoid. He had previously been prescribed sitagliptin 50 mg daily for
      at least one year prior to onset of his disease. The medication was discontinued
      and the patient was treated with first IV and then oral steroids with good
      clinical outcome. There have been a few reports that have explored the
      relationship between DPP-IV inhibitors (gliptins) and bullous pemphigoid,
      including three case series and a report on sitagliptin associated allergic skin
      reactions submitted to the Adverse Event Reports System database of the FDA.
      According to the Naranjo ADR probability score there is a "possible" cause and
      effect relationship for this case. CONCLUSION: The enzyme DPP-IV is ubiquitously
      expressed in almost every organ system, including the skin. The exact mechanism
      at this time is unknown but is believed to be multifactorial involving many
      aspects of the immune system. Our case and the findings from our literature
      review further demonstrate a link between dipeptidyl peptidase-IV inhibitors and
      the development of bullous pemphigoid.

PMID- 24748909
TI  - Two Egyptian cases of lipoid proteinosis successfully treated with acitretin.
AB  - BACKGROUND: Lipoid proteinosis (Urbach-Wiethe disease) is a rare progressive
      autosomal recessive disorder, characterized histologically by deposition of
      periodic acid Schiff-positive, diastase resistant, hyaline-like material into the
      skin, upper aerodigestive tract, and internal organs. MAIN OBSERVATION: We report
      two cases of lipoid proteinosis. A 2-year-old girl presented with vesiculobullous
      skin lesions on her face, trunk, extremities and scalp, inability to protrude the
      tongue and hoarseness of voice that appeared few months after birth. The other
      case is a 4-year-old girl, who presented with waxy papules on face and trunk,
      hoarseness of voice and enlarged lips and tongue. The lesions healed leaving
      pitted scars in both cases. Based on clinical, histopathological and laryngoscopy
      findings, lipoid proteinosis was diagnosed in both cases. Acitretin was started
      in a dose of 0.5 mg/kg/day in every child. Complete remission of cutaneous
      lesions and improvement of the hoarseness was observed after one year.
      CONCLUSION: Acitretin may be benificial for treatment of mucosal and cutaneous
      lesions in lipoid proteinosis.

PMID- 24748910
TI  - Pancreatic panniculitis - a cutaneous manifestation of acute pancreatitis.
AB  - BACKGROUND: Pancreatic panniculitis is a rare complication of pancreatic disease
      occurring in 2% to 3% of all patients, most commonly those with acute or chronic
      pancreatitis. MAIN OBSERVATIONS: We report the case of a pancreatic panniculitis
      associated with acute pancreatitis in a 63-year-old man. He presented with a 2
      day history of multiple tender subcutaneous nodules, followed by nausea,
      vomiting, severe epigastric pain and loss of appetite, hours before admission.
      Laboratory and radiologic findings revealed acute pancreatitis. Histopathological
      examination from a skin biopsy specimen taken from a nodule showed a mostly
      lobular panniculitis with "ghost cells", without vasculitis. Nodules disappeared
      with the resolution of acute pancreatic inflammation, as amylase and lipase
      levels returned to normal. CONCLUSIONS: Panniculitis may be the first
      manifestation of pancreatic disease. Therefore clinicians must have a high index
      of suspicion for the diagnosis of pancreatic panniculitis.

PMID- 24748911
TI  - Evaluation of a chronic disease management system for the treatment and
      management of diabetes in primary health care practices in Ontario: an
      observational study.
AB  - BACKGROUND: Computerized chronic disease management systems (CDMSs), when aligned
      with clinical practice guidelines, have the potential to effectively impact
      diabetes care. OBJECTIVE: The objective was to measure the difference between
      optimal diabetes care and actual diabetes care before and after the introduction
      of a computerized CDMS. METHODS: This 1-year, prospective, observational,
      pre/post study evaluated the use of a CDMS with a diabetes patient registry and
      tracker in family practices using patient enrolment models. Aggregate practice
      level data from all rostered diabetes patients were analyzed. The primary outcome
      measure was the change in proportion of patients with up-to-date "ABC" monitoring
      frequency (i.e., hemoglobin A1c, blood pressure, and cholesterol). Changes in the
      frequency of other practice care and treatment elements (e.g., retinopathy
      screening) were also determined. Usability and satisfaction with the CDMS were
      measured. RESULTS: Nine sites, 38 health care providers, and 2,320 diabetes
      patients were included. The proportion of patients with up-to-date ABC (12%),
      hemoglobin A1c (45%), and cholesterol (38%) monitoring did not change over the
      duration of the study. The proportion of patients with up-to-date blood pressure
      monitoring improved, from 16% to 20%. Data on foot examinations, retinopathy
      screening, use of angiotensin-converting enzyme inhibitors/angiotensin II
      receptor blockers, and documentation of self-management goals were not available
      or not up to date at baseline for 98% of patients. By the end of the study,
      attitudes of health care providers were more negative on the Training,
      Usefulness, Daily Practice, and Support from the Service Provider domains of the
      CDMS, but more positive on the Learning, Using, Practice Planning, CDMS, and
      Satisfaction domains. LIMITATIONS: Few practitioners used the CDMS, so it was
      difficult to draw conclusions about its efficacy. Simply giving health care
      providers a potentially useful technology will not ensure its use. CONCLUSIONS:
      This real-world evaluation of a web-based CDMS for diabetes failed to impact
      physician practice due to limited use of the system. PLAIN LANGUAGE SUMMARY:
      Patients and health care providers need timely access to information to ensure
      proper diabetes care. This study looked at whether a computer-based system at the
      doctor's office could improve diabetes management. However, few clinics and
      health care providers used the system, so no improvement in diabetes care was
      seen.

PMID- 24748912
TI  - Graphitic Carbon Nitride Supported Catalysts for Polymer Electrolyte Fuel Cells.
AB  - Graphitic carbon nitrides are investigated for developing highly durable Pt
      electrocatalyst supports for polymer electrolyte fuel cells (PEFCs). Three
      different graphitic carbon nitride materials were synthesized with the aim to
      address the effect of crystallinity, porosity, and composition on the catalyst
      support properties: polymeric carbon nitride (gCNM), poly(triazine) imide carbon
      nitride (PTI/Li+Cl-), and boron-doped graphitic carbon nitride (B-gCNM).
      Following accelerated corrosion testing, all graphitic carbon nitride materials
      are found to be more electrochemically stable compared to conventional carbon
      black (Vulcan XC-72R) with B-gCNM support showing the best stability. For the
      supported catalysts, Pt/PTI-Li+Cl- catalyst exhibits better durability with only
      19% electrochemical surface area (ECSA) loss versus 36% for Pt/Vulcan after 2000
      scans. Superior methanol oxidation activity is observed for all graphitic carbon
      nitride supported Pt catalysts on the basis of the catalyst ECSA.

PMID- 24748913
TI  - How to integrate biological research into society and exclude errors in
      biomedical publications? Progress in theoretical and systems biology releases
      pressure on experimental research.
AB  - This brief opinion proposes measures to increase efficiency and exclude errors in
      biomedical research under the existing dynamic situation. Rapid changes in
      biology began with the description of the three dimensional structure of DNA 60
      years ago; today biology has progressed by interacting with computer science and
      nanoscience together with the introduction of robotic stations for the
      acquisition of large-scale arrays of data. These changes have had an increasing
      influence on the entire research and scientific community. Future advance demands
      short-term measures to ensure error-proof and efficient development. They can
      include the fast publishing of negative results, publishing detailed methodical
      papers and excluding a strict connection between career progression and
      publication activity, especially for younger researchers. Further development of
      theoretical and systems biology together with the use of multiple experimental
      methods for biological experiments could also be helpful in the context of years
      and decades. With regards to the links between science and society, it is
      reasonable to compare both these systems, to find and describe specific features
      for biology and to integrate it into the existing stream of social life and
      financial fluxes. It will increase the level of scientific research and have
      mutual positive effects for both biology and society. Several examples are given
      for further discussion. 

PMID- 24748914
TI  - T-type Ca(2+) channels: New players in the aging brain.
AB  - Perhaps one of the most remarkable features of T-type calcium channels is their
      low-threshold of activation that makes these channels important candidates for
      calcium entry near the resting membrane potential of neurons. Hence, they mediate
      low-threshold burst discharges that occur during different forms of neuronal
      rhythmogenesis, but play also important roles in sensory transmission, as well as
      hormone and neurotransmitter release. Additionally, they have been implicated in
      an increasing number of neuronal pathologies including neuropathy, autism
      spectrum disorders and some forms of epilepsy. More recently, an implication of T
      type calcium channel in the processing of Amyloid Precursor Protein was
      documented, with possible implication in the pathogenesis of Alzheimer's disease.

PMID- 24748915
TI  - Physiological stress responses predict sexual functioning and satisfaction
      differently in women who have and have not been sexually abused in childhood.
AB  - Physiological responses to sexual stimuli may contribute to the increased rate of
      sexual problems seen in women with childhood sexual abuse (CSA) histories. We
      compared two physiological stress responses as predictors of sexual function and
      satisfaction, sympathetic nervous system (SNS) activation and cortisol in women
      with (CSA, N = 136) and without CSA histories (NSA, N = 102). In CSA survivors,
      cortisol response to sexual stimuli did not significantly predict sexual
      functioning; however, in NSA women, cortisol increases were associated with
      poorer sexual functioning, and decreases with higher functioning. For women with
      CSA histories, lower SNS activity was associated with poorer sexual functioning.
      For CSA survivors with low lifetime trauma, lower SNS activity was associated
      with higher sexual satisfaction; for women with high lifetime trauma, the reverse
      was true. Decreased SNS activity during sexual stimuli predicted higher sexual
      functioning in NSA women with low lifetime exposure to traumatic events, but
      lower sexual functioning in those with high exposure. Differences between women
      with and without CSA histories in the association between cortisol and SNS
      response and sexual functioning and satisfaction suggests that CSA causes
      disruptions in both short and long-term stress responses to sexual stimuli that
      perpetuate into adulthood.

PMID- 24748916
TI  - Transumbilical laparoscopic-assisted appendectomy in children: Clinical and
      surgical outcomes.
AB  - The aim of this paper is to present and describe transumbilical laparoscopic
      assisted appendectomy in children, focusing on its technical aspects and clinical
      and surgical outcomes. The surgical charts of all patients aged between 0 and 14
      years treated with transumbilical laparoscopic-assisted appendectomy admitted to
      the authors' institution from January 2009 to September 2013 with a diagnosis of
      suspected appendicitis following clinical, laboratory and ultrasound findings
      were reviewed. Operating time, intraoperative findings, need for conversion or
      for additional trocars, and surgical complications were reported. During the
      study period, 120 patients aged between 6 and 14 years (mean age: 9.9 years), 73
      females (61%) and 47 males (39%), were treated with transumbilical laparoscopic
      assisted appendectomy. There were 37 cases of hyperemic appendicitis (subserosal
      and retrocecal), 74 cases of phlegmonous appendicitis and 9 cases of perforated
      gangrenous appendicitis. It was not possible to establish a correlation between
      grade of appendicitis and mean operating time (P > 0.05). Eleven cases (9%)
      needed the use of one additional trocar, while 8 patients (6%) required
      conversion to the standard laparoscopic technique with the use of two additional
      trocars. No patient was converted to the open technique. Transumbilical
      laparoscopic-assisted appendectomy is a safe technique in children and it could
      be used by surgeons who want to approach other minimally invasive techniques.

PMID- 24748917
TI  - Childhood achalasia: A comprehensive review of disease, diagnosis and therapeutic
      management.
AB  - Achalasia is an esophageal motility disorder characterized by failure of lower
      esophageal sphincter (LES) relaxation and is rare in children. The most common
      symptoms are vomiting, dysphagia, regurgitation, and weight loss. Definitive
      diagnosis is made with barium swallow study and esophageal manometry. In adults,
      endoscopic biopsy is recommended to exclude malignancy however; it is not as
      often indicated in children. Medical management often fails resulting in
      recurrent symptoms and the ultimate definitive treatment is surgical.
      Laparoscopic Heller myotomy with or without an anti-reflux procedure is the
      treatment of choice and has become standard of care for children with achalasia.
      Peroral endoscopic myotomy is a novel therapy utilized with increasing frequency
      for achalasia treatment in adults. More experience is needed to determine the
      safety, efficacy, and feasibility of peroral endoscopic myotomy in children. 

PMID- 24748918
TI  - ESD training: A challenging path to excellence.
AB  - Endoscopic submucosal dissection (ESD) has important advantages over endoscopic
      mucosal resection (EMR) for early gastrointestinal neoplasia treatment, but its
      difficult learning curve and associated risks have constrained its wider
      expansion. ESD training includes a comprehensive study of ESD basics, attending
      live cases and performing initial interventions in animal models, ideally under
      expert supervision. Mentoring methods in Japan and other Asian countries are
      reviewed, with a special concern in the conditions recommended for trainees to
      engage in an ESD program and achieve competence. Animal training is usually based
      on the well-known porcine model. Ex vivo models for esophageal, gastric and
      rectal ESD are cheap and easy to set up, whereas in vivo training requires
      special settings and veterinarian support. Nevertheless, it is advisable to gain
      experience in the live pig, with conditions that are similar to humans, before
      moving on to real patients. Particular attention is focused on colorectal ESD (CR
      ESD), one of the most difficult locations for this technique. Since most of the
      potential lesions for ESD in Western countries are located in the colon or
      rectum, excellence in training is of paramount importance for successful outcomes
      in CR-ESD in the West. 

PMID- 24748919
TI  - Current status and future applications of contrast-enhanced endoscopic
      ultrasonography.
AB  - Endoscopic ultrasonography (EUS) is currently an integral investigation of many
      gastrointestinal disorders. It has been shown to have a higher efficacy than
      conventional computed tomography in detection and characterization of small
      lesions especially in the pancreas. Much effort has been put to further improve
      the sensitivity, specificity and overall accuracy of EUS. One of the major
      advances is the utilization of contrast agents for better delineation of the
      vascularity and tissue perfusion of the target lesion. This article describes the
      basic principles of ultrasound contrast agents and the different modalities used
      in contrast-enhanced EUS (CE-EUS) including contrast-enhanced Doppler EUS (CED
      EUS) and contrast-enhanced harmonic EUS (CEH-EUS). In addition, the current
      applications of contrast enhanced EUS in different gastrointestinal conditions
      were discussed. Furthermore, the future development of hybrid approaches
      combining CE-EUS with other imaging modalities and the potential therapeutic
      aspect of using it as a vector for drug delivery were also discussed. 

PMID- 24748920
TI  - Accuracy of transnasal endoscopy with a disposable esophagoscope compared to
      conventional endoscopy.
AB  - AIM: To assess feasibility of unsedated esophagoscopy using a small-caliber
      disposable transnasal esophagoscopy and to compare its accuracy with standard
      endoscopy. METHODS: We prospectively included subjects who were referred for
      upper endoscopy. All subjects underwent transnasal endoscopy with E.G. ScanTM.
      The disposable probe has a 3.6 mm gauge and at its distal end there is a 6 mm
      optical capsule, with a viewing angle of 125 degrees . Patients underwent
      conventional endoscopy after the completion of E.G. ScanTM. We describe the
      findings detected by the E.G. ScanTM and calculate the diagnostic accuracy,
      sensitivity, specificity, positive predictive value, negative predictive value
      and Kappa index for esophageal diagnosis. RESULTS: A total of 96 patients (54
      women), mean age of 50.12 years (14 to 79), were evaluated. In all cases we were
      able to perform esophagoscopy with E.G. ScanTM. The average realization time was
      5 min. A total of 58 alterations were detected in the esophagus, 49 gastric
      abnormalities and 13 duodenal abnormalities. We found that for esophageal
      varices, E.G. ScanTM has sensitivity, specificity and diagnostic accuracy of 95%,
      97% and 97%, respectively. Kappa coefficients were 0.32 for hiatal hernia, 0.409
      for erosive gastroesophageal reflux disease, 0.617 for Barrett's esophagus, and
      0.909 for esophageal varices. CONCLUSION: Esophagoscopy with E.G. ScanTM is a
      well-tolerated, fast and safe procedure. It has an appropriate diagnostic
      accuracy for esophageal varices when compared with conventional endoscopy.

PMID- 24748921
TI  - Efficacy of SpyGlass(TM)-directed biopsy compared to brush cytology in obtaining
      adequate tissue for diagnosis in patients with biliary strictures.
AB  - AIM: To evaluate the diagnostic yield (inflammatory activity) and efficiency
      (size of the biopsy specimen) of SpyGlass(TM)-guided biopsy vs standard brush
      cytology in patients with and without primary sclerosing cholangitis (PSC).
      METHODS: At the University Medical Center Mainz, Germany, 35 consecutive patients
      with unclear biliary lesions (16 patients) or long-standing PSC (19 patients)
      were screened for the study. All patients underwent a physical examination, lab
      analyses, and abdominal ultrasound. Thirty-one patients with non-PSC strictures
      or with PSC were scheduled to undergo endoscopic retrograde cholangiography (ERC)
      and subsequent peroral cholangioscopy (POC). Standard ERC was initially
      performed, and any lesions or strictures were localized. POC was performed later
      during the same session. The Boston Scientific SpyGlass System(TM) (Natick, MA,
      United States) was used for choledochoscopy. The biliary tree was visualized, and
      suspected lesions or strictures were biopsied, followed by brush cytology of the
      same area. The study endpoints (for both techniques) were the degree of
      inflammation, tissue specimen size, and the patient populations (PSC vs non-PSC).
      Inflammatory changes were divided into three categories: none, low activity, and
      high activity. The specimen quantity was rated as low, moderate, or sufficient.
      RESULTS: SpyGlass(TM) imaging and brush cytology with material retrieval were
      performed in 29 of 31 (93.5%) patients (23 of the 29 patients were male). The
      median patient age was 45 years (min, 20 years; max, 76 years). Nineteen patients
      had known PSC, and 10 showed non-PSC strictures. No procedure-related
      complications were encountered. However, for both methods, tissues could only be
      retrieved from 29 patients. In cases of inflammation of the biliary tract, the
      diagnostic yield of the SpyGlass(TM)-directed biopsies was greater than that
      using brush cytology. More tissue material was obtained for the biopsy method
      than for the brush cytology method (P = 0.021). The biopsies showed significantly
      more inflammatory characteristics and greater inflammatory activity compared to
      the cytological investigation (P = 0.014). The greater quantity of tissue samples
      proved useful for both PSC and non-PSC patients. CONCLUSION: SpyGlass(TM) imaging
      can be recommended for proper inflammatory diagnosis in PSC patients. However,
      its value in diagnosing dysplasia was not addressed in this study and requires
      further investigation.

PMID- 24748922
TI  - Rare presentation of primary (AL) amyloidosis as gastrointestinal hemorrhage
      without systemic involvement.
AB  - We are reporting a rare case of a patient with primary (AL) amyloidosis
      presenting with an acute non-variceal upper gastrointestinal hemorrhage in the
      absence of other systemic involvement. The case report involves a 58-year-old
      woman with significant cardiac history and hereditary blood disorder who came in
      complaining of abdominal pain and coffee-ground emesis for two days. Computed
      tomography (CT) scan of the abdomen and pelvis with contrast revealed segmental
      wall thickening of the proximal jejunum with hyperdense, heterogenous luminal
      content. Similar findings were evident in the left lower small bowel region,
      suspicious for small bowel hematoma and the possibility of intraluminal clots.
      Esophagogastroduodenoscopy performed post resuscitation showed punctate,
      erythematous lesions throughout the stomach as well as regions of small bowel
      mucosa that appeared scalloped, ulcerated, and hemorrhaged on contact. Despite
      initial treatment for immunostain-positive focal cytomegalovirus gastritis,
      follow-up esophagogastroduodenoscopy after two months continued to demonstrate
      friable and irregular duodenal mucosa hinting at a different underlying etiology.
      Pathology reports from analyses of biopsy samples highlighted infiltration and
      expansion of the lamina propria and submucosa. Subsequent staining with congo
      red/crystal violet and appropriate subtyping established the diagnosis of AL
      (kappa)-type amyloidosis. The significance of this case lies in the fact that our
      patient did not have the typically seen diagnostic systemic involvements-namely
      of heart and kidneys-usually seen in primary (AL) amyloidosis patients. It was
      the persistent endoscopic findings and biopsy results which gave clues to the
      physicians regarding the possibility of an abnormal protein-deposition entity. 

PMID- 24748923
TI  - Antidiabetic treatment, stroke severity and outcome.
AB  - Ischemic stroke is a leading cause of mortality and long-term disability
      worldwide. Given the detrimental effects of acute stroke, several neuroprotective
      agents have been evaluated in these patients. However, the benefits of the
      evaluated agents appear to be limited and none is currently recommended for
      clinical use. On the other hand, prior treatment with agents that are used for
      the primary and secondary prevention of stroke, including statins and
      antiplatelets, has been associated with better outcome in patients who experience
      an acute stroke. In contrast, there are limited data as to whether prior
      treatment with antidiabetic agents is beneficial in diabetic patients who suffer
      a stroke. In this context, the findings of a recent study that showed reduced
      stroke size following pretreatment with linagliptin, a dipeptidyl peptidase-4
      (DDP-4) inhibitor, compared with glimepiride, in both diabetic and non-diabetic
      mice, appear promising. Despite these preclinical findings suggesting
      neuroprotective effects of DPP-4 inhibitors in acute stroke, it is still unclear
      whether these actions will also be observed in humans. Of note, two recent large
      randomized, placebo-controlled studies did not show any effect of DPP-4
      inhibitors on cardiovascular events, including stroke. Several other ongoing
      trials are evaluating the effects of DPP-4 inhibitors on cardiovascular morbidity
      and mortality. These studies also provide a major opportunity to assess whether
      patients treated with this class of antidiabetic agents will suffer from less
      severe strokes and whether their outcome after stroke will be more favorable. 

PMID- 24748924
TI  - Expression quantitative trait analyses to identify causal genetic variants for
      type 2 diabetes susceptibility.
AB  - Type 2 diabetes (T2D) is a common metabolic disorder which is caused by multiple
      genetic perturbations affecting different biological pathways. Identifying
      genetic factors modulating the susceptibility of this complex heterogeneous
      metabolic phenotype in different ethnic and racial groups remains challenging.
      Despite recent success, the functional role of the T2D susceptibility variants
      implicated by genome-wide association studies (GWAS) remains largely unknown.
      Genetic dissection of transcript abundance or expression quantitative trait
      (eQTL) analysis unravels the genomic architecture of regulatory variants.
      Availability of eQTL information from tissues relevant for glucose homeostasis in
      humans opens a new avenue to prioritize GWAS-implicated variants that may be
      involved in triggering a causal chain of events leading to T2D. In this article,
      we review the progress made in the field of eQTL research and knowledge gained
      from those studies in understanding transcription regulatory mechanisms in human
      subjects. We highlight several novel approaches that can integrate eQTL analysis
      with multiple layers of biological information to identify ethnic-specific causal
      variants and gene-environment interactions relevant to T2D pathogenesis. Finally,
      we discuss how the eQTL analysis mediated search for "missing heritability" may
      lead us to novel biological and molecular mechanisms involved in susceptibility
      to T2D. 

PMID- 24748925
TI  - Platelet thromboxane (11-dehydro-Thromboxane B2) and aspirin response in patients
      with diabetes and coronary artery disease.
AB  - Aspirin (ASA) irreversibly inhibits platelet cyclooxygenase-1 (COX-1) leading to
      decreased thromboxane-mediated platelet activation. The effect of ASA ingestion
      on thromboxane generation was evaluated in patients with diabetes (DM) and
      cardiovascular disease. Thromboxane inhibition was assessed by measuring the
      urinary excretion of 11-dehydro-thromboxane B2 (11dhTxB2), a stable metabolite of
      thromboxane A2. The mean baseline urinary 11dhTxB2 of DM was 69.6% higher than
      healthy controls (P = 0.024): female subjects (DM and controls) had 50.9% higher
      baseline 11dhTxB2 than males (P = 0.0004), while age or disease duration had no
      influence. Daily ASA ingestion inhibited urinary 11dhTxB2 in both DM (71.7%) and
      controls (75.1%, P < 0.0001). Using a pre-established cut-off of 1500 pg/mg of
      urinary 11dhTxB2, there were twice as many ASA poor responders (ASA "resistant")
      in DM than in controls (14.8% and 8.4%, respectively). The rate of ASA poor
      responders in two populations of acute coronary syndrome (ACS) patients was 28.6
      and 28.7%, in spite of a significant (81.6%) inhibition of urinary 11dhTxB2 (P <
      0.0001). Both baseline 11dhTxB2 levels and rate of poor ASA responders were
      significantly higher in DM and ACS compared to controls. Underlying systemic
      oxidative inflammation may maintain platelet function in atherosclerotic
      cardiovascular disease irrespective of COX-1 pathway inhibition and/or increase
      systemic generation of thromboxane from non-platelet sources. 

PMID- 24748926
TI  - Recent advances in the molecular genetics of type 2 diabetes mellitus.
AB  - Type 2 diabetes mellitus (T2DM) is a complex disease in which both genetic and
      environmental factors interact in determining impaired beta-cell insulin
      secretion and peripheral insulin resistance. Insulin resistance in muscle, liver
      and fat is a prominent feature of most patients with T2DM and obesity, resulting
      in a reduced response of these tissues to insulin. Considerable evidence has been
      accumulated to indicate that heredity is a major determinant of insulin
      resistance and T2DM. It is believed that, among individuals destined to develop
      T2DM, hyperinsulinemia is the mechanism by which the pancreatic beta-cell
      initially compensates for deteriorating peripheral insulin sensitivity, thus
      ensuring normal glucose tolerance. Most of these people will develop T2DM when
      beta-cells fail to compensate. Despite the progress achieved in this field in
      recent years, the genetic causes of insulin resistance and T2DM remain elusive.
      Candidate gene association, linkage and genome-wide association studies have
      highlighted the role of genetic factors in the development of T2DM. Using these
      strategies, a large number of variants have been identified in many of these
      genes, most of which may influence both hepatic and peripheral insulin
      resistance, adipogenesis and beta-cell mass and function. Recently, a new gene
      has been identified by our research group, the HMGA1 gene, whose loss of function
      can greatly raise the risk of developing T2DM in humans and mice. Functional
      genetic variants of the HMGA1 gene have been associated with insulin resistance
      syndromes among white Europeans, Chinese individuals and Americans of Hispanic
      ancestry. These findings may represent new ways to improve or even prevent T2DM. 

PMID- 24748927
TI  - Role of P2X7 receptors in the development of diabetic retinopathy.
AB  - The P2X7 receptor is one of the members of the family of purinoceptors which are
      ligand-gated membrane ion channels activated by extracellular adenosine 5'
      triphosphate. A unique feature of the P2X7 receptor is that its activation can
      result in the formation of large plasma membrane pores that allow not only the
      flux of ions but also of hydrophilic molecules of up to 900 Da. Recent studies
      indicate that P2X7-mediated signaling can trigger apoptotic cell death after
      ischemia and during the course of certain neurodegenerative disorders. Expression
      of the P2X7 receptor has been demonstrated in most types of cells in the retina.
      This purinoceptor mediates the contraction of pericytes and regulates the spatial
      and temporal dynamics of the vasomotor response through cell-to-cell electrotonic
      transmission within the microvascular networks. Of potential clinical
      significance, investigators have found that diabetes markedly boosts the
      vulnerability of retinal microvessels to the lethal effect of P2X7 receptor
      activation. This purinergic vasotoxicity may result in reduced retinal blood flow
      and disrupted vascular function in the diabetic retina. With recent reports
      indicating an association between P2X7 receptor activation and inflammatory
      cytokine expression in the retina, this receptor may also exacerbate the
      development of diabetic retinopathy by a mechanism involving inflammation. 

PMID- 24748928
TI  - Knockout mouse models of insulin signaling: Relevance past and future.
AB  - Insulin resistance is a hallmark of type 2 diabetes. In an effort to understand
      and treat this condition, researchers have used genetic manipulation of mice to
      uncover insulin signaling pathways and determine the effects of their
      perturbation. After decades of research, much has been learned, but the
      pathophysiology of insulin resistance in human diabetes remains controversial,
      and treating insulin resistance remains a challenge. This review will discuss
      limitations of mouse models lacking select insulin signaling molecule genes. In
      the most influential mouse models, glucose metabolism differs from that of humans
      at the cellular, organ, and whole-organism levels, and these differences limit
      the relevance and benefit of the mouse models both in terms of mechanistic
      investigations and therapeutic development. These differences are due partly to
      immutable differences in mouse and human biology, and partly to the failure of
      genetic modifications to produce an accurate model of human diabetes. Several
      factors often limit the mechanistic insights gained from experimental mice to the
      particular species and strain, including: developmental effects, unexpected
      metabolic adjustments, genetic background effects, and technical issues. We
      conclude that the limitations and weaknesses of genetically modified mouse models
      of insulin resistance underscore the need for redirection of research efforts
      toward methods that are more directly relevant to human physiology. 

PMID- 24748929
TI  - Chromium does not belong in the diabetes treatment arsenal: Current evidence and
      future perspectives.
AB  - Chromium is considered to have positive effects on insulin sensitivity and is
      marketed as an adjunctive therapy for inducing glucose tolerance in cases of
      insulin resistance ("the glucose tolerance factor"). Case reports on patients who
      received prolonged parenteral nutrition indeed showed that the absence of
      trivalent chromium caused insulin resistance and diabetes. However, whether
      patients with type 2 diabetes can develop a clinically relevant chromium
      deficiency is unclear. This review summarizes the available evidence regarding
      the potential effectiveness of chromium supplementation on glycemic control
      (Hemoglobin A1c levels) in patients with type 2 diabetes. No studies
      investigating the long-term safety of chromium in humans were found. All clinical
      trials that have been performed had a relative short follow-up period. None of
      the trials investigated whether the patients had risk factors for chromium
      deficiency. The evidence from randomized trials in patients with type 2 diabetes
      demonstrated that chromium supplementation does not effectively improve glycemic
      control. The meta-analyses showed that chromium supplementation did not improve
      fasting plasma glucose levels. Moreover, there were no clinically relevant
      chromium effects on body weight in individuals with or without diabetes. Future
      studies should focus on reliable methods to estimate chromium status to identify
      patients at risk for pathological alterations in their metabolism associated with
      chromium deficiency. Given the present data, there is no evidence that supports
      advising patients with type 2 diabetes to take chromium supplements. 

PMID- 24748930
TI  - Origin and therapy for hypertriglyceridaemia in type 2 diabetes.
AB  - Hypertriglyceridaemia (HTG) is a risk factor for cardiovascular disease (CVD) in
      type 2 diabetes and is caused by the interaction of genes and non-genetic
      factors, specifically poor glycaemic control and obesity. In spite of statin
      treatment, residual risk of CVD remains high in type 2 diabetes, and this may
      relate to HTG and atherogenic dyslipidemia. Treatment of HTG emphasises
      correcting secondary factors and adverse lifestyles, in particular, diet and
      exercise. Pharmacotherapy is also required in most type 2 diabetic patients.
      Statins are the first-line therapy to achieve recommended therapeutic targets of
      plasma low-density lipoprotein cholesterol and non-high-density lipoprotein
      cholesterol. Fibrates, ezetimibe and n-3 fatty acids are adjunctive treatment
      options for residual and persistent HTG. Evidence for the use of niacin has been
      challenged by non-significant CVD outcomes in two recent large clinical trials.
      Further investigation is required to clarify the use of incretin-based therapies
      for HTG in type 2 diabetes. Extreme HTG, with risk of pancreatitis, may require
      insulin infusion therapy or apheresis. New therapies targeting HTG in diabetes
      need to be tested in clinical endpoint trials. The purpose of this review is to
      examine the current evidence and provide practical guidance on the management of
      HTG in type 2 diabetes. 

PMID- 24748932
TI  - Glycemic control indicators in patients with neonatal diabetes mellitus.
AB  - Neonatal diabetes mellitus (NDM) is a type of diabetes mellitus caused by genetic
      abnormality which develops in insulin dependent state within 6 mo after birth.
      HbA1c is widely used in clinical practice for diabetes mellitus as the gold
      standard glycemic control indicator; however, fetal hemoglobin (HbF) is the main
      hemoglobin in neonates and so HbA1c cannot be used as a glycemic control
      indicator in NDM. Glycated albumin (GA), another glycemic control indicator, is
      not affected by HbF. We reported that GA can be used as a glycemic control
      indicator in NDM. However, it was later found that because of increased
      metabolism of albumin, GA shows an apparently lower level in relation to plasma
      glucose in NDM; measures to solve this problem were needed. In this review, we
      outlined the most recent findings concerning glycemic control indicators in
      neonates or NDM. 

PMID- 24748933
TI  - Exploration of natural enzyme inhibitors with hypoglycemic potentials amongst
      Eucalyptus Spp. by in vitro assays.
AB  - AIM: To investigate the presence and potency of natural enzyme inhibitors with
      hypoglycemic potentials amongst Eucalyptus Spp. by in vitro assays. METHODS: The
      leaf extracts of the three different Eucalyptus species [E. globulus (EG), E.
      citriodora (EC), E. camaldulensis (ECA)] were subjected to in vitro assay
      procedures to explore the prevalence of natural enzyme inhibitors (NEIs) after
      preliminary qualitative and quantitative phytochemical evaluations, to study
      their inhibitory actions against the enzymes like alpha-amylase, alpha
      glucosidase, aldose reductase, angiotensin converting enzyme and dipeptidyl
      peptidase 4 playing pathogenic roles in type 2 diabetes. The antioxidant
      potential and total antioxidant capacity of the species were also evaluated.
      RESULTS: Major bioactive compounds like polyphenols (341.75 +/- 3.63 to 496.85 +/
      3.98) and flavonoids (4.89 +/- 0.01 to 7.15 +/- 0.02) were found in appreciable
      quantity in three species. Based on the IC50 values of the extracts under
      investigation, in all assays the effectivity was in the order of EG > ECA > EC.
      The results of the ferric reducing antioxidant power assay showed that the
      reducing ability of the species was also in the order of EG > ECA > EC. A strong
      correlation (R(2) = 0.81-0.99) was found between the phenolic contents and the
      inhibitory potentials of the extracts against the targeted enzymes. CONCLUSION:
      These results show immense hypoglycemic potentiality of the Eucalyptus Spp. and a
      remarkable source of NEIs for a future phytotherapeutic approach in Type 2
      diabetes.

PMID- 24748931
TI  - Phytotherapy in diabetes: Review on potential mechanistic perspectives.
AB  - Diabetes mellitus (DM) is a widely spread epidemic disease that results from the
      absence of insulin, decreased secretion and/or impaired function. Since DM is a
      multi-factorial disease, the available pharmaceuticals, despite their sensible
      treatment, target mostly one pathway to control hyperglycemia and encounter
      several side effects. Therefore, new therapeutic paradigms aim to hit several
      pathways using only one agent. Traditionally, antidiabetic plants and/or their
      active constituents may fulfill this need. More than 200 species of plants
      possess antidiabetic properties which were evaluated mostly by screening tests
      without digging far for the exact mode of action. Searching among the different
      literature resources and various database and in view of the above aspects, the
      present article provides a comprehensive review on the available antidiabetic
      plants that have been approved by pharmacological and clinical evaluations, and
      which their mechanism(s) of action is assured. These plants are categorized
      according to their proved mode of action and are classified into those that act
      by inhibiting glucose absorption from intestine, increasing insulin secretion
      from the pancreas, inhibiting glucose production from hepatocytes, or enhancing
      glucose uptake by adipose and muscle tissues. The current review also highlights
      those that mimic in their action the new peptide analogs, such as exenatide,
      liraglutide and dipeptidylpeptidase-4 inhibitors that increase glucagon-like
      peptide-1 serum concentration and slow down the gastric emptying. 

PMID- 24748934
TI  - Toll-like receptor expression and signaling in human diabetic wounds.
AB  - AIM: To examine the contribution of toll-like receptors (TLRs) expression and
      activation to the prolonged inflammation often seen in human diabetic wounds.
      METHODS: Debridement wound tissue was collected from diabetic patients with
      informed consent. Total RNA and protein were isolated and subjected to real-time
      polymerase chain reaction and Western blot analyses. RESULTS: TLR1, 2, 4, and 6
      mRNA expressions were increased significantly in wounds of diabetic patients
      compared with non-diabetic wounds (P < 0.05). MyD88 protein expression was
      significantly increased in diabetic wounds compared to non-diabetic wounds.
      Interleukin-1beta, tumor necrosis factor-alpha concentration nuclear factor-kappa
      B activation, and thiobarbituric acid reactive substances were increased in
      diabetic wounds compared to non-diabetic wounds (P < 0.01). CONCLUSION:
      Collectively, our novel findings show that increased TLR expression, signaling,
      and activation may contribute to the hyper inflammation in the human diabetic
      wounds.

PMID- 24748936
TI  - Radiation safety for pain physicians: technique or equipment.

PMID- 24748935
TI  - Gas-forming liver abscess associated with rapid hemolysis in a diabetic patient.
AB  - We experienced a case of liver abscess due to Clostridium perfringens (CP)
      complicated with massive hemolysis and rapid death in an adequately controlled
      type 2 diabetic patient. The patient died 6 h after his first visit to the
      hospital. CP was later detected in a blood culture. We searched for case reports
      of CP septicemia and found 124 cases. Fifty patients survived, and 74 died. Of
      the 30 patients with liver abscess, only 3 cases survived following treatment
      with emergency surgical drainage. For the early detection of CP infection,
      detection of Gram-positive rods in the blood or drainage fluid is important.
      Spherocytes and ghost cells indicate intravascular hemolysis. The prognosis is
      very poor once massive hemolysis occurs. The major causative organisms of gas
      forming liver abscess in diabetic patients are Klebsiella pneumoniae (K.
      pneumoniae) and Escherichia coli (E. coli). Although CP is relatively rare, the
      survival rate is very poor compared with those of K. pneumoniae and E. coli.
      Therefore, for every case that presents with a gas-forming liver abscess, the
      possibility of CP should be considered, and immediate aspiration of the abscess
      and Gram staining are important. 

PMID- 24748937
TI  - Rediscovery of nefopam for the treatment of neuropathic pain.
AB  - Nefopam (NFP) is a non-opioid, non-steroidal, centrally acting analgesic drug
      that is derivative of the non-sedative benzoxazocine, developed and known in
      1960s as fenazocine. Although the mechanisms of analgesic action of NFP are not
      well understood, they are similar to those of triple neurotransmitter (serotonin,
      norepinephrine, and dopamine) reuptake inhibitors and anticonvulsants. It has
      been used mainly as an analgesic drug for nociceptive pain, as well as a
      treatment for the prevention of postoperative shivering and hiccups. Based on
      NFP's mechanisms of analgesic action, it is more suitable for the treatment of
      neuropathic pain. Intravenous administration of NFP should be given in single
      doses of 20 mg slowly over 15-20 min or with continuous infusion of 60-120 mg/d
      to minimize adverse effects, such as nausea, cold sweating, dizziness,
      tachycardia, or drowsiness. The usual dose of oral administration is three to six
      times per day totaling 90-180 mg. The ceiling effect of its analgesia is
      uncertain depending on the mechanism of pain relief. In conclusion, the recently
      discovered dual analgesic mechanisms of action, namely, a) descending pain
      modulation by triple neurotransmitter reuptake inhibition similar to
      antidepressants, and b) inhibition of long-term potentiation mediated by NMDA
      from the inhibition of calcium influx like gabapentinoid anticonvulsants or
      blockade of voltage-sensitive sodium channels like carbamazepine, enable NFP to
      be used as a therapeutic agent to treat neuropathic pain. 

PMID- 24748938
TI  - Median nerve injuries caused by carpal tunnel injections.
AB  - Local steroid injections are widely used for diagnostic and therapeutic purposes
      in the management of carpal tunnel syndrome. The median nerve injury is the most
      serious complication in association with carpal tunnel injections although the
      incidence is low. A median nerve injury will be presented with shooting pain at
      the injection time along with other sensory distortion, motor weakness and muscle
      atrophy. The management includes a conservative treatment and a surgical
      exploration. Carpal tunnel injections should be used at a minimum only. If such
      steroid injection is required, an appropriate needle positioning is vital for the
      nerve injury prevention. The patient should not be heavily sedated and should be
      encouraged to inform experiences of numbness/paresthesia during the procedure
      immediately. 

PMID- 24748939
TI  - Acute systemic infusion of bupropion decrease formalin induced pain behavior in
      rat.
AB  - BACKGROUND: The chronic pain can disturb physical, psychological, and social
      performances. Analgesic agents are widely used but some antidepressants (ADs)
      showed analgesia also. Bupropion is using for smoke cessation but it can change
      morphine withdrawal signs such as pain. This study tested the acute systemic
      effect of bupropion on formalin induced pain behavior in rats. METHODS: Wistar
      male healthy rats were divided into 7 groups (control, sham, and 5 treated groups
      with 10, 30, 90, 120, and 200 mg/kg of bupropion, i.p.). The bupropion injected 3
      hours prior to formalin induced pain behavior. Formalin (50 ul, 2.5%) was
      injected subcutaneously in dorsal region of right hindpaw in all animals.
      Nociceptive signs were observed continuously on-line and off-line each minute.
      Common pain scoring was used for pain assessment. RESULTS: The analysis of data
      by one-way ANOVA showed that bupropion can reduce pain scores in the second phase
      but not in first phase. Bupropion decreased the licking/biting duration
      significantly in first and second phase of formalin test. CONCLUSIONS: The
      results showed that bupropion has analgesic effects at systemic application. The
      change of second phase of the pain behavior was significant and it revealed that
      central mechanisms involve in bupropion analgesia.

PMID- 24748940
TI  - Feasibility of Early and Repeated Low-dose Interscalene Brachial Plexus Block for
      Residual Pain in Acute Cervical Radiculopathy Treated with NSAIDS.
AB  - BACKGROUND: To improve residual pain management in acute cervical radiculopathy
      treated with NSAIDs, the feasibility of early and repeated low-dose interscalene
      brachial plexus block (IS-BPB) needs to be assessed. METHODS: This was a
      prospective study on patients receiving NSAIDs (loxoprofen) for cervical
      radiculopathy of <= 2-week onset. Pain was assessed using the visual analogue
      scale (VAS). A low-dose ultrasonography (USG)-guided IS-BPB (dexamethasone [1.65
      mg; 0.5 ml] and mepivacaine [1%; 3.0 ml]) was performed at baseline and weekly
      thereafter for 4 weeks in an outpatient setting for the intervention group. All
      patients were evaluated using a visual satisfaction score (VSS) at week 4.
      Patients with baseline VAS scores < 70 (mild to moderate pain; MM group) and >=
      70 (severe pain; SE group) were compared to the controls receiving NSAIDs.
      RESULTS: A total of 316 IS-BPBs were performed in the intervention group. There
      was a significant difference in the decline in the VAS from week 0 to week 3 in
      the MM and SE groups (P < 0.05); however, from week 3 to week 4, the therapeutic
      effect exhibited no significant difference. Thirteen patients at week 2 (15.5%;
      MM: 27.7%; SE: 0%), 43 at week 3 (51.2%; MM: 83.0%; SE: 10.8%), and 47 at week 4
      (56.0%; MM: 85.1%; SE: 18.9%) achieved a VAS score of <= 20. Patient satisfaction
      was high, and the decrease in VAS scores in both groups was significant (P <
      0.05) compared to the controls. CONCLUSIONS: Weekly, low-dose, USG-guided IS-BPB
      can be implemented for early pain relief in acute cervical radiculopathy, with
      high patient satisfaction.

PMID- 24748941
TI  - Survey of sonoanatomic distances for lumbar medial branch nerve blocks in healthy
      volunteers.
AB  - BACKGROUND: The precise knowledge of anatomy and the region of transverse process
      (TP) and superior articular processes (AP) and their distance from the skin are
      important in blocking and treating lumbar facet syndrome. Evaluation of these
      anatomic distances from 3rd and 5th lumbar vertebrae in both sides and in
      different body mass index (BMI) in healthy volunteers might improve knowledge of
      ultrasound (US) lumbar medial branch nerve blocks (LMBB). METHODS: Bilateral US
      in the 3rd and 5th lumbar vertebrae of 64 volunteers carried out and the distance
      between skin to TP and skin to AP was measured. These distances were compared on
      both sides and in different BMI groups. The analysis was done using SPSS 11.
      Analysis of variance was used to compare the means at three vertebral levels (L3
      L5) and different BMI groups. P values less than 0.05 were considered
      statistically significant. The paired t-test was used to compare the mean
      distance between skin to TP and skin to AP on both sides. RESULTS: The distance
      between skin to TP and skin to AP of 3rd vertebrae to 5th vertebrae was increased
      in both right and left sides (P < 0.001) from up to down. The mean distance from
      skin to TP were greater on the left side compared to the right in all three
      vertebral levels from L3 to L5 (P values 0.014, 0.024, and 0.006 respectively).
      The mean distance from skin to TP and the skin to AP was statistically
      significant in different BMI groups (P < 0.001). CONCLUSIONS: We found many
      anatomic distances which may increase awareness of US guided LMBB.

PMID- 24748942
TI  - Epidural Infusion of Morphine and Levobupivacaine through a Subcutaneous Port for
      Cancer Pain Management.
AB  - BACKGROUND: To manage intractable cancer pain, an alternative to systemic
      analgesics is neuraxial analgesia. In long-term treatment, intrathecal
      administration could provide a more satisfactory pain relief with lower doses of
      analgesics and fewer side-effects than that of epidural administration. However,
      implantable drug delivery systems using intrathecal pumps in Korea are very
      expensive. Considering cost-effectiveness, we performed epidural analgesia as an
      alternative to intrathecal analgesia. METHODS: We retrospectively investigated
      the efficacy, side effects, and complications of epidural morphine and local
      anesthetic administration through epidural catheters connected to a subcutaneous
      injection port in 29 Korean terminal cancer patients. Patient demographic data,
      the duration of epidural administration, preoperative numerical pain rating
      scales (NRS), side effects and complications related to the epidural
      catheterization and the drugs, and the numerical pain rating scales on the 1st,
      3rd, 7th and 30th postoperative days were determined from the medical records.
      RESULTS: The average score for the numerical pain rating scales for the 29
      patients decreased from 7 +/- 1.0 at baseline to 3.6 +/- 1.4 on postoperative day
      1 (P < 0.001). A similar decrease in pain intensity was maintained for 30 days (P
      < 0.001). Nausea and vomiting were the most frequently reported side effects of
      the epidural analgesia and two patients (6.9%) experienced paresthesia.
      CONCLUSIONS: Epidural morphine and local anesthetic infusion with a subcutaneous
      pump seems to have an acceptable risk-benefit ratio and allows a high degree of
      autonomy to patients with cancer pain.

PMID- 24748943
TI  - How Effective Are Radiation Reducing Gloves in C-arm Fluoroscopy-guided Pain
      Interventions?
AB  - BACKGROUND: The physician's hands are close to the X-ray field in C-arm
      fluoroscopy-guided pain interventions. We prospectively investigated the
      radiation attenuation of Proguard RR-2 gloves. METHODS: In 100 cases, the
      effective doses (EDs) of two dosimeters without a radiation-reducing glove were
      collected. EDs from the two dosimeters-one dosimeter wrapped with a glove and the
      other dosimeter without a glove- were also measured at the side of the table
      (Group 1, 140 cases) and at a location 20 cm away from the side of the table
      (Group 2, 120 cases). Mean differences such as age, height, weight, radiation
      absorbed dose (RAD), exposure time, ED, and ratio of EDs were analyzed. RESULTS:
      In the EDs of two dosimeters without gloves, there were no significant
      differences (39.0 +/- 36.3 uSv vs. 38.8 +/- 36.4 uSv) (P = 0.578). The RAD (192.0
      +/- 182.0 radcm(2)) in Group 2 was higher than that (132.3 +/- 103.5 radcm(2)) in
      Group 1 (P = 0.002). The ED (33.3 +/- 30.9 uSv) of the dosimeter without a glove
      in Group 1 was higher than that (12.3 +/- 8.8 uSv) in Group 2 (P < 0.001). The ED
      (24.4 +/- 22.4 uSv) of the dosimeter wrapped with a glove in Group 1 was higher
      than that (9.2 +/- 6.8 uSv) in Group 2 (P < 0.001). No significant differences
      were noted in the ratio of EDs (73.5 +/- 6.7% vs. 74.2 +/- 9.3%, P = 0.469)
      between Group 1 and Group 2. CONCLUSIONS: Proguard RR-2 gloves have a radiation
      attenuation effect of 25.8-26.5%. The radiation attenuation is not significantly
      different by intensity of scatter radiation or the different RADs of C-arm
      fluoroscopy.

PMID- 24748944
TI  - Model determination of delayed causes of analgesics prescription in the emergency
      ward in arak, iran.
AB  - BACKGROUND: According to the reports of the World Health Organization 20% of
      world population suffer from pain and 33% of them suffer to some extent that they
      cannot live independently. METHODS: This is a cross-sectional study which was
      conducted in the emergency department (ED) of Valiasr Hospital of Arak, Iran, in
      order to determine the causes of delay in prescription of analgesics and to
      construct a model for prediction of circumstances that aggravate oligoanalgesia.
      Data were collected during a period of 7 days. RESULTS: Totally, 952 patients
      participated in this study. In order to reduce their pain intensity, 392 patients
      (42%) were treated. Physicians and nurses recorded the intensity of pain for
      66.3% and 41.37% of patients, respectively. The mean (SD) of pain intensity
      according to visual analogue scale (VAS) was 8.7 (1.5) which reached to 4.4 (2.3)
      thirty minutes after analgesics prescription. Median and mean (SD) of delay time
      in injection of analgesics after the physician's order were 60.0 and 45.6 (63.35)
      minutes, respectively. The linear regression model suggested that when the
      attending physician was male or intern and patient was from rural areas the delay
      was longer. CONCLUSIONS: We propose further studies about analgesics
      administration based on medical guidelines in the shortest possible time and also
      to train physicians and nurses about pain assessment methods and analgesic
      prescription.

PMID- 24748945
TI  - The Radiation Exposure of Radiographer Related to the Location in C-arm
      Fluoroscopy-guided Pain Interventions.
AB  - BACKGROUND: Although a physician may be the nearest to the radiation source
      during C-arm fluoroscope-guided interventions, the radiographer is also near the
      fluoroscope. We prospectively investigated the radiation exposure of
      radiographers relative to their location. METHODS: The effective dose (ED) was
      measured with a digital dosimeter on the radiographers' left chest and the side
      of the table. We observed the location of the radiographers in each procedure
      related to the mobile support structure of the fluoroscope (Groups A, M and P).
      Data about age, height, weight, sex, exposure time, radiation absorbed dose
      (RAD), and the ED at the radiographer's chest and the side of the table was
      collected. RESULTS: There were 51 cases for Group A, 116 cases for Group M and
      144 cases for Group P. No significant differences were noted in the demographic
      data such as age, height, weight, and male to female ratio, and exposure time,
      RAD and ED at the side of the table. Group P had the lowest ED (0.5 +/- 0.8 uSv)
      of all the groups (Group A, 1.6 +/- 2.3 uSv; Group M, 1.3 +/- 1.9 uSv; P <
      0.001). The ED ratio (ED on the radiographer's chest/ED at the side of the table)
      of Group A was the highest, and the ED radio of Group P was the lowest of all the
      groups (Group A, 12.2 +/- 21.5%; Group M, 5.7 +/- 6.5%; Group P, 2.5 +/- 6.7%; P
      < 0.001). CONCLUSIONS: Radiographers can easily reduce their radiation exposure
      by changing their position. Two steps behind the mobile support structure can
      effectively decrease the exposure of radiographers by about 80%.

PMID- 24748946
TI  - Analysis of Inadvertent Intradiscal Injections during Lumbar Transforaminal
      Epidural Injection.
AB  - BACKGROUND: Recently, there have been several case reports and retrospective
      studies about the incidence of intradiscal (ID) injection during transforaminal
      epidural steroid injection (TFESI). Inadvertent ID injection is not a rare
      complication, and it carries the risk of developing diskitis, although there has
      been no report of diskitis after TFESI. We prospectively evaluated the incidence
      of inadvertent ID injection during lumbar TFESI and analyzed the contributing
      factors. METHODS: Ten patients received 2-level TFESI, and the remaining 229
      patients received 1-level TFESI. When successful TFESI was performed, 2 ml of
      contrast dye was injected under real-time fluoroscopy to check for any
      inadvertent ID spread. A musculoskeletal radiologist analyzed all magnetic
      resonance images (MRIs) of patients who demonstrated inadvertent ID injection.
      When reviewing MRIs, the intervertebral foramen level where ID injection occurred
      was carefully examined, and any anatomical structure which narrowing the foramen
      was identified. RESULTS: Among the 249 TFESI, we identified 6 ID injections;
      thus, there was an incidence of 2.4%. Four patients had isthmic
      spondylolisthesis, and the level of spondylolisthesis coincided with the level of
      ID injection. We further examined the right or left foramen of the
      spondylolisthesis level and identified the upward migrated disc material that was
      narrowing the foramen. CONCLUSIONS: Inadvertent ID injection during TFESI is not
      infrequent, and pain physicians must pay close attention to the type and location
      of disc herniation.

PMID- 24748947
TI  - Glomus tumor causing anterior thigh pain: a case report.
AB  - Glomus tumors are a rare, benign neoplasm and 75% exist in the subungual region.
      Extradigital glomus tumors are much more difficult to diagnose because of their
      atypical location and symptoms. Furthermore, if their symptoms are similar to
      neuropathic pain, the patient can suffer from misdirected treatment due to
      misdiagnosis. It is essential to perform careful evaluation of the lesion itself
      in order to reduce misdiagnosis. Ultrasonography is a useful, non-invasive method
      that can be easily performed in the pain clinic for local evaluation and
      diagnosis. We report a case of misdiagnosed glomus tumor in the thigh which was
      properly diagnosed after ultrasonography. 

PMID- 24748948
TI  - A novel balloon-inflatable catheter for percutaneous epidural adhesiolysis and
      decompression.
AB  - Epidural adhesions cause pain by interfering with the free movement of the spinal
      nerves and increasing neural sensitivity as a consequence of neural compression.
      To remove adhesions and deliver injected drugs to target sites, percutaneous
      epidural adhesiolysis (PEA) is performed in patients who are unresponsive to
      conservative treatments. We describe four patients who were treated with a newly
      developed inflatable balloon catheter for more effective PEA and relief of
      stenosis. In the present patients, treatments with repetitive epidural steroid
      injection and/or PEA with the Racz catheter or the NaviCath did not yield long
      lasting effects or functional improvements. However, PEA and decompression with
      the inflatable balloon catheter led to maintenance of pain relief for more than
      seven months and improvements in the functional status with increases in the
      walking distance. The present case series suggests that the inflatable balloon
      catheter may be an effective alternative to performing PEA when conventional
      methods fail to remove adhesions or sufficiently relieve stenosis. 

PMID- 24748949
TI  - Chicken and egg: peripheral nerve entrapment or myofascial trigger point?

PMID- 24748950
TI  - Knowledge, Perceptions and Acceptability to Strengthening Adolescents' Sexual and
      Reproductive Health Education amongst Secondary Schools in Gulu District.
AB  - Adolescents in Northern Uganda are at risk of teenage pregnancies, unsafe
      abortions and sexually transmitted infections (STIs). There is silence on sex
      both at home and school. This cross sectional descriptive analytical study
      interviews a random sample of 827 students and 13 teachers on knowledge,
      perception and acceptability to a comprehensive adolescent sexual and
      reproductive health education in "O" and "A" level secondary schools in Gulu
      District. Quantitative data was analysed using SPSS 16.0. Directed content
      analysis of themes of transcribed qualitative data was conducted manually for
      common codes, sub-categories and categories. Of the 827 students; 54.3% (449)
      reported being in a sexual relationship especially those aged 15-17 years.
      Majority 96.1% (807) supported the teaching of a comprehensive ASRHE, citing no
      negative impact 71.5% (601). Majority 81.6% (686) agreed that such education
      could help prevention of STIs, abortions and teenage pregnancies, and that it
      should be taught by health workers 69.0% (580). Majority 76.6% (203) reported
      that ASRHE was not currently being taught in their schools. Students had low
      knowledge levels and misconceptions about ASRHE. ASRHE was highly acceptable
      though not being emphasized; its success in school settings requires
      multidisciplinary culturally sensitive approaches amongst which health workers
      should be frontiers.

PMID- 24748952
TI  - Nanobiomechanics of living cells: a review.
AB  - Nanobiomechanics of living cells is very important to understand cell-materials
      interactions. This would potentially help to optimize the surface design of the
      implanted materials and scaffold materials for tissue engineering. The
      nanoindentation techniques enable quantifying nanobiomechanics of living cells,
      with flexibility of using indenters of different geometries. However, the data
      interpretation for nanoindentation of living cells is often difficult. Despite
      abundant experimental data reported on nanobiomechanics of living cells, there is
      a lack of comprehensive discussion on testing with different tip geometries, and
      the associated mechanical models that enable extracting the mechanical properties
      of living cells. Therefore, this paper discusses the strategy of selecting the
      right type of indenter tips and the corresponding mechanical models at given test
      conditions. 

PMID- 24748951
TI  - Introduction to cell-hydrogel mechanosensing.
AB  - The development of hydrogel-based biomaterials represents a promising approach to
      generating new strategies for tissue engineering and regenerative medicine. In
      order to develop more sophisticated cell-seeded hydrogel constructs, it is
      important to understand how cells mechanically interact with hydrogels. In this
      paper, we review the mechanisms by which cells remodel hydrogels, the influence
      that the hydrogel mechanical and structural properties have on cell behaviour and
      the role of mechanical stimulation in cell-seeded hydrogels. Cell-mediated
      remodelling of hydrogels is directed by several cellular processes, including
      adhesion, migration, contraction, degradation and extracellular matrix
      deposition. Variations in hydrogel stiffness, density, composition, orientation
      and viscoelastic characteristics all affect cell activity and phenotype. The
      application of mechanical force on cells encapsulated in hydrogels can also
      instigate changes in cell behaviour. By improving our understanding of cell
      material mechano-interactions in hydrogels, this should enable a new generation
      of regenerative medical therapies to be developed. 

PMID- 24748953
TI  - Collective cell traction force analysis on aligned smooth muscle cell sheet
      between three-dimensional microwalls.
AB  - During the past two decades, novel biomaterial scaffold for cell attachment and
      culture has been developed for applications in tissue engineering, biosensing and
      regeneration medicine. Tissue engineering of blood vessels remains a challenge
      owing to the complex three-layer histology involved. In order to engineer
      functional blood vessels, it is essential to recapitulate the characteristics of
      vascular smooth muscle cells (SMCs) inside the tunica media, which is known to be
      critical for vasoconstriction and vasodilation of the circulatory system. Until
      now, there has been a lack of understanding on the mechanotransduction of the SMC
      layer during the transformation from viable synthetic to quiescent contractile
      phenotypes. In this study, microfabricated arrays of discontinuous microwalls
      coated with fluorescence microbeads were developed to probe the
      mechanotransduction of the SMC layer. First, the system was exploited for
      stimulating the formation of a highly aligned orientation of SMCs in native
      tunica medium. Second, atomic force microscopy in combination with regression
      analysis was applied to measure the elastic modulus of a polyacrylamide gel layer
      coated on the discontinuous microwall arrays. Third, the conventional traction
      force assay for single cell measurement was extended for applications in three
      dimensional cell aggregates. Then, the biophysical effects of discontinuous
      microwalls on the mechanotransduction of the SMC layer undergoing cell alignment
      were probed. Generally, the cooperative multiple cell-cell and cell-microwall
      interactions were accessed quantitatively by the newly developed assay with the
      aid of finite-element modelling. The results show that the traction forces of
      highly aligned cells lying in the middle region between two opposing microwalls
      were significantly lower than those lying adjacent to the microwalls. Moreover,
      the spatial distributions of Von Mises stress during the cell alignment process
      were dependent on the collective cell layer orientation. Immunostaining of the
      SMC sheet further demonstrated that the collective mechanotransduction induced by
      three-dimensional topographic cues was correlated with the reduction of actin and
      vinculin expression. In addition, the online two-dimensional LC-MS/MS analysis
      verified the modulation of focal adhesion formation under the influence of
      microwalls through the regulation in the expression of three key cytoskeletal
      proteins. 

PMID- 24748954
TI  - The structure and micromechanics of elastic tissue.
AB  - Elastin is a major component of tissues such as lung and blood vessels, and
      endows them with the long-range elasticity necessary for their physiological
      functions. Recent research has revealed the complexity of these elastin
      structures and drawn attention to the existence of extensive networks of fine
      elastin fibres in tissues such as articular cartilage and the intervertebral
      disc. Nonlinear microscopy, allowing the visualization of these structures in
      living tissues, is informing analysis of their mechanical properties. Elastic
      fibres are complex in composition and structure containing, in addition to
      elastin, an array of microfibrillar proteins, principally fibrillin. Raman
      microspectrometry and X-ray scattering have provided new insights into the
      mechanisms of elasticity of the individual component proteins at the molecular
      and fibrillar levels, but more remains to be done in understanding their
      mechanical interactions in composite matrices. Elastic tissue is one of the most
      stable components of the extracellular matrix, but impaired mechanical function
      is associated with ageing and diseases such as atherosclerosis and diabetes.
      Efforts to understand these associations through studying the effects of
      processes such as calcium and lipid binding and glycation on the mechanical
      properties of elastin preparations in vitro have produced a confusing picture,
      and further efforts are required to determine the molecular basis of such
      effects. 

PMID- 24748955
TI  - Dynamics of filopodium-like protrusion and endothelial cellular motility on one
      dimensional extracellular matrix fibrils.
AB  - Endothelial filopodia play key roles in guiding the tubular sprouting during
      angiogenesis. However, their dynamic morphological characteristics, with the
      associated implications in cell motility, have been subjected to limited
      investigations. In this work, the interaction between endothelial cells and
      extracellular matrix fibrils was recapitulated in vitro, where a specific focus
      was paid to derive the key morphological parameters to define the dynamics of
      filopodium-like protrusion during cell motility. Based on one-dimensional gelatin
      fibrils patterned by near-field electrospinning (NFES), we study the response of
      endothelial cells (EA.hy926) under normal culture or ROCK inhibition. It is shown
      that the behaviour of temporal protrusion length versus cell motility can be
      divided into distinct modes. Persistent migration was found to be one of the
      modes which permitted cell displacement for over 300 um at a speed of
      approximately 1 um min(-1). ROCK inhibition resulted in abnormally long
      protrusions and diminished the persistent migration, but dramatically increased
      the speeds of protrusion extension and retraction. Finally, we also report the
      breakage of protrusion during cell motility, and examine its phenotypic
      behaviours. 

PMID- 24748956
TI  - A hybrid characterization framework to determine the visco-hyperelastic
      properties of a porcine zona pellucida.
AB  - The zona pellucida (ZP) is a specialized extracellular matrix surrounding the
      developing oocyte. This thick matrix consists of various types of glycoprotein
      that play different roles in the fertilization process. Nowadays, several
      techniques are available for assessing ZP's mechanical response. The basic
      assumption behind these methods is that the ZP behaves like an elastic body:
      hence, dissipative forces are neglected and Young's modulus remains unaffected by
      probe dynamics. However, dissipative forces are strongly regulated by the
      slippage of ZP chains past one another while reaction forces related to elastic
      deformations (driven by the ability of each chain to stretch) depend on the ZP
      structure (i.e. number of cross-links and distances between knots). Although
      viscous reaction forces generated by the ZP are one of the main factors
      regulating sperm transit, their peculiar behaviour along the ZP structure remains
      poorly understood and rarely investigated. In order to overcome this limitation,
      a novel visco-hyperelastic model describing the porcine ZP reaction forces
      generated by nanoindentations at different probe rates is developed and verified
      in this study. Visco-hyperelastic parameters of porcine ZP membranes are
      determined by means of a hybrid characterization framework combining atomic force
      microscopy nanoindentation measurements, nonlinear finite-element analysis and
      nonlinear optimization. Remarkably, it is possible to separate the contributions
      of hyperelastic and viscous terms to ZP mechanical response and evaluate the
      error made in the determination of ZP mechanical properties if viscous effects
      were not considered. 

PMID- 24748957
TI  - Impact of heating on passive and active biomechanics of suspended cells.
AB  - A cell is a complex material whose mechanical properties are essential for its
      normal functions. Heating can have a dramatic effect on these mechanical
      properties, similar to its impact on the dynamics of artificial polymer networks.
      We investigated such mechanical changes by the use of a microfluidic optical
      stretcher, which allowed us to probe cell mechanics when the cells were subjected
      to different heating conditions at different time scales. We find that HL60/S4
      myeloid precursor cells become mechanically more compliant and fluid-like when
      subjected to either a sudden laser-induced temperature increase or prolonged
      exposure to higher ambient temperature. Above a critical temperature of 52 +/- 1
      degrees C, we observed active cell contraction, which was strongly correlated
      with calcium influx through temperature-sensitive transient receptor potential
      vanilloid 2 (TRPV2) ion channels, followed by a subsequent expansion in cell
      volume. The change from passive to active cellular response can be effectively
      described by a mechanical model incorporating both active stress and viscoelastic
      components. Our work highlights the role of TRPV2 in regulating the
      thermomechanical response of cells. It also offers insights into how cortical
      tension and osmotic pressure govern cell mechanics and regulate cell-shape
      changes in response to heat and mechanical stress. 

PMID- 24741437
TI  - The beauty of being (label)-free: sample preparation methods for SWATH-MS and
      next-generation targeted proteomics.
AB  - The combination of qualitative analysis with label-free quantification has
      greatly facilitated the throughput and flexibility of novel proteomic techniques.
      However, such methods rely heavily on robust and reproducible sample preparation
      procedures. Here, we benchmark a selection of in gel, on filter, and in solution
      digestion workflows for their application in label-free proteomics. Each
      procedure was associated with differing advantages and disadvantages. The in gel
      methods interrogated were cost effective, but were limited in throughput and
      digest efficiency. Filter-aided sample preparations facilitated reasonable
      processing times and yielded a balanced representation of membrane proteins, but
      led to a high signal variation in quantification experiments. Two in solution
      digest protocols, however, gave optimal performance for label-free proteomics. A
      protocol based on the detergent RapiGest led to the highest number of detected
      proteins at second-best signal stability, while a protocol based on acetonitrile
      digestion, RapidACN, scored best in throughput and signal stability but came
      second in protein identification. In addition, we compared label-free data
      dependent (DDA) and data independent (SWATH) acquisition on a TripleTOF 5600
      instrument. While largely similar in protein detection, SWATH outperformed DDA in
      quantification, reducing signal variation and markedly increasing the number of
      precisely quantified peptides. 

PMID- 24741439
TI  - Fiberoptic monitoring of central venous oxygen saturation (PediaSat) in small
      children undergoing cardiac surgery: continuous is not continuous.
AB  - BACKGROUND:  Monitoring of superior vena cava saturation (ScvO 2) has become
      routine in the management of pediatric patients undergoing cardiac surgery. The
      objective of our study was to evaluate the correlation between continuous ScvO 2
      by the application of a fiber-optic oximetry catheter (PediaSat) and intermittent
      ScvO 2 by using standard blood gas measurements. These results were compared to
      those obtained by cerebral near infrared spectroscopy (cNIRS). SETTING:  Tertiary
      pediatric cardiac intensive care unit (PCICU). METHODS AND MAIN RESULTS:  A
      retrospective study was conducted in consecutive patients who were monitored with
      a 4.5 or 5.5 F PediaSat catheter into the right internal jugular vein. An  in
      vivo calibration was performed once the patient was transferred to the PCICU and
      re-calibration took place every 24 hours thereafter. Each patient had a NIRS
      placed on the forehead. Saturations were collected every 4 hours until
      extubation. Ten patients with a median age of 2.2 (0.13-8.5) years and a weight
      of 12.4 (3.9-24) kg were enrolled. Median sampling time was 32 (19-44) hours: 64
      pairs of PediaSat and ScVO2 saturations showed a poor correlation (r=0.62, 95% CI
      44-75; p<0.0001) and Bland Altman analysis for repeated measures showed an
      average difference of 0.34 with a standard deviation of 7,9 and 95% limits of
      agreement from -15 to 16. Thirty-six pairs of cNIRS and ScVO2 saturations showed
      a fair correlation (r=0.79, 95% CI 0.60-0.89; p<0.0001) an average difference of 
      1.4 with a standard deviation of 6 and 95% limits of agreement from -13 to 10.
      Analysis of median percentage differences between PediaSat and ScvO2 saturation
      over time revealed that, although not statistically significant, the change in
      percentage saturation differences was clinically relevant after the 8th hour from
      calibration (from -100 to +100%). CONCLUSION:  PediaSat catheters showed
      unreliable performance in our cohort. It should be further investigated whether
      repeating calibrations every 8 hours may improve the accuracy of this system.
      CNIRS may provide similar results with a lower invasiveness.

PMID- 24741438
TI  - Validation of predicted mRNA splicing mutations using high-throughput
      transcriptome data.
AB  - Interpretation of variants present in complete genomes or exomes reveals numerous
      sequence changes, only a fraction of which are likely to be pathogenic. Mutations
      have been traditionally inferred from allele frequencies and inheritance patterns
      in such data. Variants predicted to alter mRNA splicing can be validated by
      manual inspection of transcriptome sequencing data, however this approach is
      intractable for large datasets. These abnormal mRNA splicing patterns are
      characterized by reads demonstrating either exon skipping, cryptic splice site
      use, and high levels of intron inclusion, or combinations of these properties. We
      present, Veridical, an in silico method for the automatic validation of DNA
      sequencing variants that alter mRNA splicing. Veridical performs statistically
      valid comparisons of the normalized read counts of abnormal RNA species in mutant
      versus non-mutant tissues. This leverages large numbers of control samples to
      corroborate the consequences of predicted splicing variants in complete genomes
      and exomes. 

PMID- 24741440
TI  - FeatureViewer, a BioJS component for visualization of position-based annotations
      in protein sequences.
AB  - SUMMARY: FeatureViewer is a BioJS component that lays out, maps, orients, and
      renders position-based annotations for protein sequences. This component is
      highly flexible and customizable, allowing the presentation of annotations by
      rows, all centered, or distributed in non-overlapping tracks. It uses either
      lines or shapes for sites and rectangles for regions. The result is a powerful
      visualization tool that can be easily integrated into web applications as well as
      documents as it provides an export-to-image functionality. AVAILABILITY:
      https://github.com/biojs/biojs/blob/master/src/main/javascript/Biojs.FeatureViewe
      .js; http://dx.doi.org/10.5281/zenodo.7719.

PMID- 24748962
TI  - Spontaneous cardiomyocyte differentiation of mouse embryoid bodies regulated by
      hydrogel crosslink density.
AB  - Cellular therapies have great potential to provide alternative treatment options
      for those suffering from heart disease. In order to optimize cell delivery for
      therapeutic efficacy, a greater understanding of parameters that impact stem cell
      differentiation, survival, growth, and development are needed. In this study, we
      examine the role of hydrogel crosslink density on spontaneous cardiomyocyte (CM)
      differentiation of murine embryoid bodies (EBs). CM differentiation was
      accelerated in hydrogels of low crosslink density, where 100% of the hydrogels
      were positive for CM differentiation compared to only 53% in the high crosslink
      density group after 8 days of culture. DNA microarray data suggests that enhanced
      CM differentiation in the low crosslink density hydrogels was not tissue specific
      but rather a result of favoured EB development and cell proliferation.
      Additionally, enhanced EB growth and differentiation in low crosslink density
      hydrogels was independent of RGD ligand density and not a consequence of enhanced
      diffusion. We also demonstrate that matrix metalloproteinase activity is required
      for spontaneous CM differentiation in 3D hydrogels. Low hydrogel crosslink
      density regulates spontaneous EB differentiation by promoting EB growth and
      development. Elucidating the effects of microenvironmental cues on cell
      differentiation can aid in the optimization of stem cell-based therapies for
      tissue regeneration.

PMID- 24748963
TI  - Hyaluronic acid hydrogel stiffness and oxygen tension affect cancer cell fate and
      endothelial sprouting.
AB  - Three-dimensional (3D) tissue culture models may recapitulate aspects of the
      tumorigenic microenvironment in vivo, enabling the study of cancer progression in
      vitro. Both hypoxia and matrix stiffness are known to regulate tumor growth.
      Using a modular culture system employing an acrylated hyaluronic acid (AHA)
      hydrogel, three hydrogel matrices with distinctive degrees of viscoelasticity -
      soft (78+/-16 Pa), medium (309+/- 57 Pa), and stiff (596+/- 73 Pa) - were
      generated using the same concentration of adhesion ligands. Oxygen levels within
      the hydrogel in atmospheric (21 %), hypoxic (5 %), and severely hypoxic (1 %)
      conditions were assessed with a mathematical model. HT1080 fibrosarcoma cells,
      encapsulated within the AHA hydrogels in high densities, generated nonuniform
      oxygen distributions, while lower cell densities resulted in more uniform oxygen
      distributions in the atmospheric and hypoxic environments. When we examined how
      varying viscoelasticity in atmospheric and hypoxic environments affects cell
      cycles and the expression of BNIP3 and BNIP3L (autophagy and apoptosis genes),
      and GLUT-1 (a glucose transport gene), we observed that HT1080 cells in 3D
      hydrogel adapted better to hypoxic conditions than those in a Petri dish, with no
      obvious correlation to matrix viscoelasticity, by recovering rapidly from
      possible autophagy/apoptotic events and alternating metabolism mechanisms.
      Further, we examined how HT1080 cells cultured in varying viscoelasticity and
      oxygen tension conditions affected endothelial sprouting and invasion. We
      observed that increased matrix stiffness reduced endothelial sprouting and
      invasion in atmospheric conditions; however, we observed increased endothelial
      sprouting and invasion under hypoxia at all levels of matrix stiffness with the
      upregulation of vascular endothelial growth factor (VEGF) and angiopoeitin-1 (ANG
      1). Overall, HT1080 cells encapsulated in the AHA hydrogels under hypoxic stress
      recovered better from apoptosis and demonstrated greater angiogenic induction.
      Thus, we propose that oxygen tension more profoundly influences cell fate and the
      angiogenic potential of 3D cultured HT1080 fibrosarcoma cells than does matrix
      stiffness.

PMID- 24748964
TI  - Regulatory role of regucalcin in heart calcium signaling: Insight into cardiac
      failure (Review).
AB  - Regucalcin was first identified in 1978 as a regulatory protein of Ca2+ signaling
      in liver cells. Regucalcin was shown to play a multifunctional role in cell
      regulation, such as maintainance of intracellular Ca2+ homeostasis and
      suppression of signal transduction, protein synthesis, nuclear function, cell
      proliferation and apoptosis in various types of cells and tissues. Cardiac
      excitation-contraction coupling is based on the regulation of intracellular Ca2+
      concentration by the Ca2+ pump in the sarcoplasmic reticulum of heart muscle
      cells. Regucalcin, which is expressed in the heart, was found to increase rat
      heart sarcoplasmic reticulum Ca2+-ATPase activity and ATP-dependent Ca2+ uptake
      and mitochondrial Ca2+-ATPase activity. Regucalcin was also shown to suppress
      Ca2+-dependent protein tyrosine phosphatase, Ca2+/calmodulin-dependent protein
      phosphatase (calcineurin) and nitric oxide (NO) synthase activity in the heart
      cytoplasm. Moreover, regucalcin was found to activate superoxide dismutase (SOD),
      which plays a significant role in the prevention of cell death and apoptosis in
      the heart. Regucalcin may be a key molecule in heart muscle cell regulation
      through Ca2+ signaling. Regucalcin may also play a pathophysiological role in
      heart failure. The aim of this study was to review the recent findings regarding
      the role of regucalcin in Ca2+ signaling in the heart.

PMID- 24748965
TI  - Current developments in forensic interpretation of mixed DNA samples (Review).
AB  - A number of recent improvements have provided contemporary forensic
      investigations with a variety of tools to improve the analysis of mixed DNA
      samples in criminal investigations, producing notable improvements in the
      analysis of complex trace samples in cases of sexual assult and homicide. Mixed
      DNA contains DNA from two or more contributors, compounding DNA analysis by
      combining DNA from one or more major contributors with small amounts of DNA from
      potentially numerous minor contributors. These samples are characterized by a
      high probability of drop-out or drop-in combined with elevated stutter,
      significantly increasing analysis complexity. At some loci, minor contributor
      alleles may be completely obscured due to amplification bias or over
      amplification, creating the illusion of additional contributors. Thus, estimating
      the number of contributors and separating contributor genotypes at a given locus
      is significantly more difficult in mixed DNA samples, requiring the application
      of specialized protocols that have only recently been widely commercialized and
      standardized. Over the last decade, the accuracy and repeatability of mixed DNA
      analyses available to conventional forensic laboratories has greatly advanced in
      terms of laboratory technology, mathematical models and biostatistical software,
      generating more accurate, rapid and readily available data for legal proceedings
      and criminal cases.

PMID- 24748966
TI  - Targeting regulatory T cells in cytokine-induced killer cell cultures (Review).
AB  - Regulatory T cells (Tregs) are potent immunosuppressive cells that promote tumor
      growth and invasion by inducing immune escape and suppressing the antitumor
      immune response. Cytokine-induced killer (CIK) cells are considered to be the
      primary candidate for adoptive immunotherapy due to their strong antitumor
      activity. It was recently reported that the concomitant presence of Tregs may
      decrease the cytotoxicity of CIK cells. Therefore, depletion or downregulation of
      Tregs in CIK cell cultures by optimizing the culture program may enhance CIK cell
      cytotoxicity in vitro and in vivo. The aim of the present review was to summarize
      the currently available studies on the optimal culture strategy for improving the
      antitumor activity of CIK cells through targeting Tregs.

PMID- 24748968
TI  - DNA methylation as an early diagnostic marker of cancer (Review).
AB  - DNA methylation is one of the essential epigenetic mechanisms that are closely
      correlated with the mechanisms underlying cell growth, differentiation and
      transformation in eukaryotes. Global changes in the epigenetic landscape are
      considered to be a hallmark of cancer. The initiation and progression of cancer
      are mediated through epigenetic modifications along with genetic alterations.
      Aberrant methylation of promoter regions is an epigenetic abnormality of the
      human genome that is highly characteristic of cancer. In this review, we aimed to
      summarize our current understanding of the alterations in the epigenetic
      landscape and investigate the potential use of DNA and RNA methylation in
      effective molecular treatment strategies.

PMID- 24748967
TI  - Family with sequence similarity 107: A family of stress responsive small proteins
      with diverse functions in cancer and the nervous system (Review).
AB  - Under conditions of acute stress, rapid adaptation is crucial for maximizing
      biological survival. The responses to environmental stress are often complex,
      involving numerous genes and integrating events at the cellular and organismal
      levels. The heat shock proteins (HSPs) are a family of highly conserved proteins
      that play critical roles in maintaining cell homeostasis and protecting cells
      under chronic and acute stress conditions. The genes for these stress-responding
      proteins are widely distributed in organisms, tissues and cells. HSPs participate
      in a variety of physiological processes and are associated with various types of
      disease. In this review, we focused on family with sequence similarity 107
      (FAM107), a novel unique protein family that exhibits functional similarity with
      HSPs during the cellular stress response. This review aimed to summarize the
      biological properties of FAM107 in cancer and the nervous system.

PMID- 24748969
TI  - Aspirin inhibit platelet-induced epithelial-to-mesenchymal transition of
      circulating tumor cells (Review).
AB  - Metastasis, a cascade of events beginning with epithelial-to-mesenchymal
      transition (EMT), is the main cause of cancer-related mortality. EMT endows
      circulating cancer cells (CTCs) with invasive and anti-apoptotic properties.
      These transitioning cells leave the primary tumor site and travel through the
      circulation to populate remote organs, even prior to the onset of clinical
      symptoms. During this journey, CTCs activate platelets, which in turn secrete
      alpha-granules. These alpha-granules contain high levels of transforming growth
      factor-beta (TGF-beta) and platelet-derived growth factor (PDGF), both considered
      to be powerful activators of EMT. Recently, regular aspirin use was associated
      with a reduced risk of cancer metastasis. However, the molecular mechanism
      underlying the chemotherapeutic effects of aspirin on metastasis has not been
      fully elucidated. As platelets lack a nucleus, regular aspirin use may exert long
      lasting effects on irreversible inhibition of cyclooxygenase (COX)-1 and,
      subsequently, the secretion of alpha-granules, which contributes to the
      maintenance of the EMT state of CTCs. Thus, we hypothesized that the inhibition
      of platelet-induced EMT of CTCs through the COX-1 signaling pathway may
      contribute to the intriguing antimetastatic potential of aspirin.

PMID- 24748970
TI  - Liposomal delivery and polyethylene glycol-liposomal oxaliplatin for the
      treatment of colorectal cancer (Review).
AB  - Oxaliplatin is effective for the treatment of advanced colorectal cancer;
      however, its application is restricted due to its dose-limiting toxicity.
      Liposomes are sphere-shaped vesicles consisting of one or more phospholipid
      bilayers. Liposomes as drug carriers are characterized by delayed release, lesion
      targeting and may be used as a drug-delivery system to decrease the side effects
      of cytotoxic drugs. Active targeting modification of liposomes may change the
      biological distribution of the anticancer agents, reduce or reverse multidrug
      resistance of tumor cells and enhance the effects of anticancer therapy. Based on
      the characteristics mentioned above, the aim of the present review was to
      demonstrate that polyethylene glycol-liposomes containing oxaliplatin may offer
      advantages for the treatment of colorectal cancer in clinical practice.

PMID- 24748971
TI  - Protein expression and gene polymorphism of CXCL10 in patients with colorectal
      cancer.
AB  - Chemokines (chemotactic cytokines) promote leukocyte attraction to sites of
      inflammation and cancer. Certain chemokines promote and regulate neoplastic
      progression, including metastasis and angiogenesis. One such chemokine, CXCL10,
      was found to be expressed in colorectal cancer (CRC) tissue. To gain insight into
      the prognostic significance of CXCL10, we investigated whether the levels of this
      chemokine were altered in the colorectal tissue or plasma of CRC patients. Using
      Luminex technology for protein analyses, we observed a significantly higher
      CXCL10 protein level in cancer tissue compared to that in paired normal tissue.
      Moreover, significantly higher plasma levels of CXCL10 were detected in patients
      compared to those in control subjects and the plasma levels of CXCL10 in
      disseminated disease were found to be significantly higher compared to those in
      localized disease. The single-nucleotide polymorphism rs8878, which has been
      described in exon 4 in the 3'-untranslated region of the CXCL10 gene, was
      investigated using a TaqMan system. There were significant differences in
      genotype distribution and allelic frequencies between CRC patients and control
      subjects. In conclusion, altered CXCL10 protein concentrations in CRC tissues or
      plasma and the rs8878 genotype variant of CXCL10 may contribute to the prediction
      of clinical outcome.

PMID- 24748972
TI  - The effects of aspirin plus cisplatin on SGC7901/CDDP cells in vitro.
AB  - The purpose of this study was to determine the effect of aspirin plus cisplatin
      (CDDP) in the chemotherapy of gastric cancer. We cultured SGC7901/CDDP cells by
      long-term exposure of SGC7901 cells to small doses of CDDP in vitro. The cells
      were treated with aspirin, CDDP or aspirin plus CDDP for 24 h and cell growth was
      assessed by the MTT assay, the apoptotic rate by flow cytometry, the survivin
      mRNA expression by RT-PCR and the survivin protein expression by western
      blotting. The results revealed that the cell growth in the aspirin plus CDDP
      group was significantly inhibited. The apoptotic rate in the aspirin plus CDDP
      was significantly higher compared to that in the other groups. The survivin mRNA
      and protein expression were also significantly reduced in the aspirin plus CDDP
      group. Our data suggest that the combination of aspirin and CDDP exhibited a
      higher degree of toxicity against SGC7901/CDDP cells compared to that of aspirin
      or CDDP alone. Thus, the combination of aspirin plus CDDP may reduce the
      expression of survivin and induce the apoptosis of SGC7901/CDDP cells.

PMID- 24748973
TI  - Heptanol decreases the incidence of ischemia-induced ventricular arrhythmias
      through altering electrophysiological properties and connexin 43 in rat hearts.
AB  - Heptanol is a type of gap junction inhibitor that decreases electrical conduction
      velocity. However, little is known regarding the effects of heptanol on the
      arrhythmias induced by regional myocardial ischemia. This study aimed to
      investigate the effects of heptanol on ventricular arrhythmias and the underlying
      mechanisms. On the Langendorff apparatus, isolated hearts of Sprague-Dawley rats
      underwent 30 min of ischemia, with or without pretreatment with heptanol (0.1,
      0.3 or 0.5 mM), 15 min prior to the induction of regional ischemia through
      ligation of the left anterior descending coronary artery. The incidence of
      ventricular tachycardia (VT) and ventricular fibrillation (VF) were recorded
      after ligation. Heptanol decreased the incidence of ventricular arrhythmias (45%
      in the control group vs. 10% in the 0.1 mM group, 0% in the 0.3 mM group and 0%
      in the 0.5 mM group, P<0.05), whereas it prolonged the PR interval, QT interval
      and monophasic action potential duration at 90% repolarization (MAPD90). As
      evaluated with immunofluorescence microscopy, heptanol was able to partly reverse
      the downregulation of connexin 43 (Cx43) induced by ischemia. The results of the
      reverse transcription-polymerase chain reaction were consistent with those of
      immunofluorescence. In conclusion, heptanol significantly decreased the incidence
      of VT and VF induced by regional ischemia and prolonged the PR interval, QT
      interval and MAPD90. Heptanol also partly reversed the downregulation of Cx43
      induced by ischemia.

PMID- 24748974
TI  - Induction of hepatic Bach1 mRNA expression by carbon tetrachloride-induced acute
      liver injury in rats.
AB  - Hepatic oxidative stress is a major contributor to the pathogenesis of several
      acute liver diseases. Diagnostic markers of hepatic oxidative stress may
      facilitate early detection and intervention. Bach1 is an oxidative stress
      responsive transcription factor that represses heme oxygenase 1 (HO-1), the rate
      limiting enzyme in the catabolism of heme, a potent pro-oxidant. We previously
      demonstrated that carbon tetrachloride (CCl4) causes oxidative hepatic injury in
      rats, exacerbated by free heme, suggesting that CCl4 may affect Bach1 gene
      expression. In the present study, we used northern blot analysis to measure
      Bach1, HO-1 and delta-aminolevulinate synthase (ALAS1; a heme biosynthesis
      enzyme) mRNA expression levels during acute hepatic injury induced by CCl4 (at
      doses of 0.1, 1.0 and 2.0 ml/kg body weight). Oxidative injury was assessed by
      measuring serum alanine aminotransferase (ALT), hepatic malondialdehyde (MDA) and
      glutathione (GSH) content. Treatment with CCl4 induced a significant dose
      dependent increase in Bach1 mRNA 1-3 h after administration. Bach1 mRNA peaked at
      6 h after CCl4 treatment (1 ml/kg), followed by a rapid decrease and gradual
      return to baseline by 12 h after treatment. The timecourse of transient Bach1
      mRNA induction roughly mirrored that of HO-1 mRNA, while ALAS1 mRNA was inversely
      downregulated. Serum ALT levels and hepatic MDA concentration were significantly
      increased at 24 h after CCl4 treatment, while the hepatic GSH content was
      significantly reduced within 3 h of treatment. Serum ALT levels were positively
      correlated with Bach1 mRNA levels. These findings indicate that Bach1 mRNA is
      transiently induced in rat liver by CCl4, possibly as a regulatory mechanism to
      restore HO-1 to baseline following free heme catabolism. Our findings also
      suggest that Bach1 mRNA expression may be a novel indicator of the extent of
      oxidative hepatic injury caused by free heme.

PMID- 24748975
TI  - Antioxidant activities of two sericin proteins extracted from cocoon of silkworm
      (Bombyx mori) measured by DPPH, chemiluminescence, ORAC and ESR methods.
AB  - Recent efforts have focused on the use of sericin proteins extracted from cocoons
      of silkworm as a healthy food source for human consumption. In this study, we
      focused on the antioxidative properties of sericin proteins. The antioxidative
      properties were measured in sericin proteins extracted from the shell of the
      cocoon, designated hereafter as white sericin protein and yellow-green sericin
      protein, as well as bread without sericin protein and bread to which white
      sericin powder had been added using four measurement methods: 1,1-Diphenyl-2
      picrylhydrazyl (DPPH), chemiluminescence, oxygen radical absorbance capacity
      (ORAC) and electron spin resonance (ESR). High antioxidative properties of
      sericin proteins were indicated by all four methods. A comparison of the two
      types of sericin proteins revealed that yellow-green sericin protein exhibited
      high antioxidative properties as indicated by the DPPH, chemiluminescence and
      ORAC methods. By contrast, a higher antioxidative property was determined in
      white sericin protein by the ESR method. Consequently, our findings confirmed
      that sericin proteins have antioxidative properties against multiple radicals. In
      addition, the antioxidative property of bread was enhanced by the addition of
      sericin powder to the bread. Therefore, findings of this study suggest that
      sericin proteins may be efficiently used as beneficial food for human health.

PMID- 24748976
TI  - Characterization of gut microbiota profiles by disease activity in patients with
      Crohn's disease using data mining analysis of terminal restriction fragment
      length polymorphisms.
AB  - The gut microbiota plays a significant role in the pathogenesis of Crohn's
      disease (CD). In this study, we analyzed the disease activity and associated
      fecal microbiota profiles in 160 CD patients and 121 healthy individuals. Fecal
      samples from the CD patients were collected during three different clinical
      phases, the active (n=66), remission-achieved (n=51) and remission-maintained
      (n=43) phases. Terminal restriction fragment length polymorphism (T-RFLP) and
      data mining analysis using the Classification and Regression Tree (C&RT) approach
      were performed. Data mining provided a decision tree that clearly identified the
      various subject groups (nodes). The majority of the healthy individuals were
      divided into Node-5 and Node-8. Healthy subjects comprised 99% of Node-5 (91 of
      92) and 84% of Node-8 (21 of 25 subjects). Node-3 was characterized by CD (136 of
      160 CD subjects) and was divided into Node-6 and Node-7. Node-6 (n=103) was
      characterized by subjects in the active phase (n=48; 46%) and remission-achieved
      phase (n=39; 38%) and Node-7 was characterized by the remission-maintained phase
      (21 of 37 subjects; 57%). Finally, Node-6 was divided into Node-9 and Node-10.
      Node-9 (n=78) was characterized by subjects in the active phase (n=43; 55%) and
      Node-10 (n=25) was characterized by subjects in the remission-maintained phase
      (n=16; 64%). Differences in the gut microbiota associated with disease activity
      of CD patients were identified. Thus, data mining analysis appears to be an ideal
      tool for the characterization of the gut microbiota in inflammatory bowel
      disease.

PMID- 24748977
TI  - CpG-oligodeoxynucleotides suppress the proliferation of A549 lung adenocarcinoma
      cells via toll-like receptor 9 signaling and upregulation of Runt-related
      transcription factor 3 expression.
AB  - The aim of the present study was to investigate the effect of CpG
      oligodeoxynucelotides (CpG-ODN) on the proliferation of the A549 human lung
      adenocarcinoma cell line and the expression of Runt-related transcription factor
      3 (Runx3) and investigate the association between the toll-like receptor 9 (TLR9)
      signaling pathway and Runx3 expression during A549 cell proliferation. Different
      concentrations of CpG-ODN were used in this study to stimulate A549 cells and the
      expression of Runx3 at the mRNA or protein level was detected by reverse
      transcription-polymerase chain reaction or western blot analysis. Moreover, Runx3
      siRNA was synthesized and transiently transfected into the A549 cells and the MTT
      assay was used to detect the effects of CpG-ODN on transfected cell growth. Our
      data demonstrated that CpG-ODN significantly inhibited the proliferation of A549
      cells. The expression of Runx3 in the mRNA and protein level was increased in
      A549 cells stimulated by CpG-ODN. The CpG-ODN-stimulated cell proliferation was
      significantly inhibited in Runx3 siRNA-transfected A549 cells. In conclusion, CpG
      ODN may bind to TLR9, inhibit the proliferation of A549 cells and upregulate the
      expression of Runx3.

PMID- 24748978
TI  - Interleukin-1alpha -899 (+4845) C->T polymorphism is not associated with
      aggressive periodontitis susceptibility: A meta-analysis based on 19 case-control
      studies.
AB  - A number of published studies investigated the association between interleukin
      1alpha (IL-1alpha) -899 (+4845) C->T polymorphism and susceptibility to
      aggressive periodontitis (AgP). However, the results from different studies are
      controversial. This study was conducted to further investigate the association
      between IL-1alpha -899 (+4845) C->T polymorphism and AgP using a meta-analysis. A
      search was conducted through PubMed up to May 1, 2013 and a total of 19 relevant
      case-control studies were identified. The results of this meta-analysis
      demonstrated that IL-1alpha -899 (+4845) C->T polymorphism is not associated with
      susceptibility to AgP under allele T vs. C [odds ratio (OR)=1.00, 95% confidence
      interval (CI): 0.88-1.14, P=0.98; I2=28.86%] or allele A vs. C comparison
      (OR=0.99, 95% CI: 0.85-1.14, P=0.85; I2=33.66%). The subgroup analyses based on
      ethnicity, source of controls and Hardy-Weinberg equilibrium (HWE) also revealed
      no such association. There existed a weak publication bias (Egger's test P=0.02).
      In conclusion, based on the currently available evidence, there is no association
      between IL-1alpha -899 (+4845) C->T polymorphism and susceptibility to AgP.

PMID- 24748979
TI  - microRNA expression patterns across seven cancers are highly correlated and
      dominated by evolutionarily ancient families.
AB  - microRNAs (miRNAs) are involved in almost all normal and pathogenic eukaryotic
      cell processes. One area in which the influence of miRNAs is most prominent is
      cancer. Numerous expression surveys and more focused studies have revealed miRNA
      involvement in carcinogenesis, cellular pathology, cell behavior and prognosis.
      Large-scale comparisons of miRNA expression in varioius types of cancer have not
      been previously possible. However, The Cancer Genome Atlas (TCGA), an extensive
      multi-centered effort to characterize the genomes of hundreds of types of cancer,
      has enabled such comparisons. In the present study, the expression patterns of
      hundreds of miRNAs in thousands of tumors covering seven types of cancer: uterine
      corpus adenocarcinoma, ovarian serous adenocarcinoma, breast adenocarcinoma,
      prostate adenocarcinoma, pancreatic adenocarcinoma, colorectal adenocarcinoma,
      and lung adenocarcinoma were analyzed. The results showed that miRNA expression
      patterns among these cancer types are highly correlated (0.874>rho>0.974) and
      that miRNA expression in all seven cancer types is dominated by miRNAs belonging
      to the most evolutionarily ancient miRNA families. This raises the possibility
      that more ancient miRNAs are involved in the fundamental cell processes that are
      central to tumor evolution.

PMID- 24748980
TI  - Arachis hypogaea L. stem and leaf extract improves the sleep behavior of
      pentobarbital-treated rats.
AB  - This study was conducted to evaluate the sedative effects of Arachis hypogaea L.
      stem and leaf extract (AHSLE) and determine its effect pathways through gamma
      aminobutyric acid (GABA)-gated channels on male Sprague-Dawley rats treated with
      pentobarbital. AHSLE was obtained from 98 degrees C water (3 h, extracted twice).
      AHSLE and flumazenil (a GABA type A receptor antagonist) were administered to the
      rats orally, whereas pentobarbital sodium and muscimol (a GABA type A receptor
      agonist) were administered intraperitoneally (i.p.). The results demonstrated
      that AHSLE decreased sleep latency and increased sleep time in pentobarbital
      treated rats (50 mg/kg, i.p.). The coadministration of AHSLE and muscimol (0.05
      mg/kg) significantly increased sleep time and reduced sleep latency in
      pentobarbital-treated rats and these actions were significantly antagonized by
      flumazenil at a dose of 3.5 mg/kg. These results indicated that AHSLE improved
      the sleep behavior in pentobarbital-treated rats, possibly through GABA-gated
      channel-related mechanisms.

PMID- 24748981
TI  - APOBEC3B gene overexpression in non-small-cell lung cancer.
AB  - Recent study results have demonstrated that a subclass of apolipoprotein B mRNA
      editing enzyme, catalytic polypeptide-like (APOBEC) cytidine deaminase may induce
      mutation clusters in various types of cancer. From the Cancer Genome Altas, an
      APOBEC mutation pattern was identified in bladder, cervical, breast, head and
      neck and lung cancers. In the present study, APOBEC3B mRNA expression was
      investigated using quantitative reverse transcription-polymerase chain reaction
      (RT-qPCR) assay using LightCycler in surgically treated non-small-cell lung
      cancer (NSCLC) cases. Additionally, 88 surgically removed Japanese NSCLC cases
      were analyzed for mRNA level. The results showed that APOBEC3B/beta-actin mRNA
      levels were significantly higher in lung cancer (1,598.481+/-6,465.781) when
      compared to adjacent normal lung tissues (2,116.639+/-8,337.331, P=0.5453). The
      tumor/normal (T/N) ratio of APOBEC3B/beta-actin mRNA levels was not different
      within the gender, age, smoking status and pathological stages. The T/N ratio of
      APOBEC3B/beta-actin mRNA levels was not significantly different in epidermal
      growth factor receptor (EGFR) or Kras mutation-positive cases as compared to the
      wild-type cases.

PMID- 24748982
TI  - Lack of association between MTHFR Ala222Val and Glu429Ala polymorphisms and
      bladder cancer risk: A meta-analysis of case-control studies.
AB  - Bladder cancer is a commom malignancy in the urinary tract that is influenced by
      genetic and environmental factors. The role of functional polymorphisms in the
      methylenetetrahydrofolate reductase (MTHFR) gene with bladder cancer risk remains
      to be determined. This meta-analysis was performed to derive a more precise
      estimation of MTHFR Ala222Val and Glu429Ala polymorphisms and bladder cancer
      risk. Data were collected with the last report up to September 2013. A total of
      3,463 cases and 3,927 controls for Ala222Val, and 3,177 cases and 3,502 controls
      for Glu429Ala were analyzed. The pooled odds ratios (ORs) and 95% confidence
      interval (CI) were estimated for the association with bladder cancer risk.
      Overall, no significant associations of Ala222Val and Glu429Ala polymorphisms
      with bladder cancer risk were found (for Ala222Val: Val/Val vs. Ala/Ala: OR,
      1.02; 95% CI: 0.80-1.29; Val/Ala vs. Ala/Ala: OR, 1.02; 95% CI: 0.92-1.12;
      dominant model: OR, 1.01; 95% CI: 0.87-1.17; recessive model: OR, 1.00; 95% CI:
      0.87-1.15; and for Glu429Ala: Ala/Ala vs. Glu/Glu: OR, 1.11; 95% CI: 0.78-1.58;
      Ala/Glu vs. Glu/Glu: OR, 1.16; 95% CI: 0.95-1.40; dominant model: OR, 1.15; 95%
      CI: 0.94-1.41; recessive model: OR, 0.96; 95% CI: 0.79-1.15). In stratified
      analyses by ethnicity, significant associations were observed for Glu429Ala
      polymorphism in individuals of Middle Eastern descent (Ala/Glu vs. Glu/Glu: OR,
      2.11; 95% CI: 1.26-3.53; dominant model: OR, 2.16; 95% CI: 1.16-4.01; recessive
      model: OR, 1.82; 95% CI: 1.11-3.01). This meta-analysis demonstrated that overall
      there was no association of MTHFR Ala222Val and Glu429Ala polymorphisms with
      bladder cancer risk. However, in the stratified analysis by ethnicity the MTHFR
      Glu429Ala polymorphism was significantly associated with increased bladder cancer
      risk in individuals of Middle Eastern descent.

PMID- 24748983
TI  - Genetic variant rs1058240 at the microRNA-binding site in the GATA3 gene may
      regulate its mRNA expression.
AB  - The GATA binding protein 3 (GATA3) is a member of a family of 6 GATA dual zinc
      finger transcription factors (GATA1-6), which are required for the development
      and morphogenesis of the mammary gland. GATA3 is considered to play a dual role
      in oncogenesis and cancer development, whereas somatic GATA3 mutations have been
      reported in breast cancer. Variants of the GATA3 genetic 3' untranslated region
      (3'UTR) microRNA (miRNA) binding sites have been associated with breast cancer
      risk. However, the roles of genetic variants in the GATA3 gene 3'UTR and its post
      transcriptional regulation have not been fully elucidated. We discovered that
      rs1058240 in the GATA3 3'UTR displayed potential miRNA binding sites and this
      variant was found to be significantly associated with GATA3 mRNA expression
      (P=2.36E-07), suggesting that rs1058240 may be a putative variant mediating the
      post-transcriptional regulation of the GATA3 target gene. Further studies
      investigating the regulatory mechanism of GATA3 transcriptional activity are
      required to design novel strategies against breast cancer cell growth and
      differentiation.

PMID- 24748984
TI  - Effect of heavy-ion beam irradiation on the level of serum soluble interleukin-2
      receptors in hamster cheek pouch carcinoma model.
AB  - Soluble interleukin-2 receptor (sIL-2R) is a glycoprotein derived from alpha
      chain of interleukin 2 receptors of mononuclear as well as T-cell membranes. The
      aims of this study were to detect the changes of serum soluble interleukin-2
      receptor (sIL-2R) levels following heavy-ion beam irradiation in the hamster
      model with cheek pouch carcinoma, as well as to examine the impact of immune
      status of the hamster cheek pouch carcinoma model using heavy-ion beam
      irradiation. sIL-2R serum levels were detected by radioimmunoassay (RIA) in 40
      hamsters bearing cheek pouch carcinoma prior to and following exposure to heavy
      ion beam irradiation, and 8 normal animals served as the control. The sIL-2R
      serum level in hamster cheek pouch carcinoma model was significantly increased as
      compared to the normal control group (P<0.05). Results showed that an increase in
      the irradiation dose led to a gradual decrease in the sIL-2R serum level.
      Additionally, a statistical significance was observed compared to the tumor group
      (P<0.05). In conclusion, alterations in serum sIL-2R expression have an effect on
      the hamsters cheek pouch carcinoma model subsequent to heavy-ion beam
      irradiation. An increase in the irradiation dose indicated a decreased tendency
      in serum sIL-2R content. Detection of serum level changes may lead to an improved
      understanding of heavy-ion irradiation in vivo immune status, which is crucial
      for clinical diagnosis and prognosis. It can also provide a sensitive indicator
      to help estimate the effects of heavy-ion cancer targets.

PMID- 24748985
TI  - Influence of celecoxib on the vasodilating properties of human mesenteric
      arteries constricted with endothelin-1.
AB  - The mitogenic and vasoconstrictive properties of the vascular system are
      attributed to endothelin-1 (ET-1). ET-1 serum concentration increases in a number
      of pathological conditions, particularly in those associated with blood vessel
      constriction. ET-1 is also associated with the underlying pathomechanisms of
      primary pulmonary hypertension, arterial hypertension and eclampsia. The aim of
      this study was to compare the vasodilating properties of selected
      phosphodiesterase (PDE) inhibitors and celecoxib in human mesenteric arteries
      constricted with ET-1, and investigate the role of the endothelium in relaxation.
      Perfused human mesenteric arteries were collected and stored under the same
      conditions as organs for transplantation. The mesenteric arteries (with and
      without the endothelium) were constricted by the addition of ET-1 and treated
      with one of the following: sildenafil (PDE5 inhibitor), zaprinast (PDE5 and 6
      inhibitor), rolipram (PDE4 inhibitor) and celecoxib [cyclooxygenase-2 (COX-2)
      inhibitor]. Based on the observed changes of the perfusion pressure,
      concentration response curves (CRCs) were prepared for the respective inhibitors
      and the EC50 (concentration causing an effect equal to half of the maximum
      effect), pD2 (negative common logarithm of EC50) and relative potency (RP) were
      calculated. The results suggested that all the inhibitors triggered a
      concentration-dependent decrease in the perfusion pressure in isolated human
      superior mesenteric arteries with endothelium constricted by the addition of ET
      1. In the arteries without endothelium, CRCs for celecoxib and rolipram were
      shifted to the right without a significant decrease in the maximum dilating
      effect. Moreover, CRCs for sildenafil and zaprinast were shifted to the right
      with a simultaneous significant decrease in the maximum dilating effect and with
      an increased inclination angle in reference to the concentration axis. In the
      presence of the endothelium, all of the evaluated PDE inhibitors, as well as
      celecoxib, reduced the reactivity of the mesenteric arteries caused by ET-1.
      Sildenafil indicated the lowest efficacy in the presence of the endothelium, but
      showed a higher potency compared to that of the other compounds. Removing the
      endothelium significantly reduced the vasodilating efficacy of PDE5 and 6
      inhibitors and a statistically significant influence on the vasodilating efficacy
      of PDE4 inhibitor and celecoxib was observed. The high vasorelaxing efficacy of
      celecoxib at the background of the PDE inhibitors was observed, not only in the
      presence, but also in the absence of the endothelium and may be evidence for the
      relaxation induced by this COX-2 inhibitor in the cAMP- and cGMP-dependent
      pathways.

PMID- 24748986
TI  - alpha-Tocopherol protects keratinocytes against ultraviolet A irradiation by
      suppressing glutathione depletion, lipid peroxidation and reactive oxygen species
      generation.
AB  - This study aimed to investigate whether alpha-tocopherol is able to protect
      keratinocytes against ultraviolet A (UVA) radiation by increasing glutathione
      (gamma-glutamylcysteinylglycine; GSH) levels or decreasing lipid peroxidation and
      reactive oxygen species (ROS) generation. The cell survival fraction was 43.6%
      when keratinocytes were irradiated with UVA at a dose of 8 J/cm2. alpha
      Tocopherol was added prior to UVA irradiation and the cell viability was assayed.
      The cell survival fractions were 60.2, 77.1, 89.0, 92.9 and 96.2% when alpha
      tocopherol was added at concentrations of 2.9, 5.9, 8.8, 11.8 and 14.7 IU/ml,
      respectively. These results suggested that alpha-tocopherol is capable of
      protecting keratinocytes against UVA irradiation. Furthermore, the levels of GSH,
      lipid peroxidation and ROS were measured. The levels of GSH were 0.354 and 0.600
      mmol/g protein in keratinocytes irradiated with UVA (8 J/cm2) and in non
      irradiated cells, respectively, whereas they were 0.364, 0.420, 0.525, 0.540 and
      0.545 mmol/g protein when alpha-tocopherol was added at concentrations of 2.9,
      5.9, 8.8, 11.8 and 14.7 IU/ml, respectively. The levels of lipid peroxidation
      were 20.401 or 5.328 MUmol/g [malondialdehyde (MDA)/protein] in keratinocytes
      irradiated with UVA (8 J/cm2) and in non-irradiated cells, respectively, whereas
      they were 11.685, 6.544, 5.847, 4.390 and 2.164 MUmol/g (MDA/protein) when alpha
      tocopherol was added at concentrations of 2.9, 5.9, 8.8, 11.8 and 14.7 IU/ml,
      respectively. The levels of ROS were 3,952.17 or 111.87 1/mg protein in
      keratinocytes irradiated with UVA (8 J/cm2) and in non-irradiated cells,
      respectively, whereas they were 742.48, 579.36, 358.16, 285.63 and 199.82 1/mg
      protein when alpha-tocopherol was added at concentrations of 2.9, 5.9, 8.8, 11.8
      and 14.7 IU/ml, respectively. These findings suggested that alpha-tocopherol
      protects keratinocytes against UVA irradiation, possibly through increasing the
      levels of GSH or decreasing the levels of lipid peroxidation and ROS generation.

PMID- 24748987
TI  - Plasma microRNA-320, microRNA-let-7e and microRNA-21 as novel potential
      biomarkers for the detection of retinoblastoma.
AB  - Retinoblastoma (RB) is a childhood malignancy caused by inactivation of the RB
      gene, with neuron-specific enolase (NSE) levels considered as its diagnostic
      marker. MicroRNAs (miRNAs) have been proven to play a significant role in
      multiple physiological and pathological processes and several miRNAs were
      identified as tumor biomarkers in recent studies. In the present study, 65 plasma
      samples were collected from RB patients and 65 samples from healthy individuals
      to serve as controls. The miRNA levels were measured via quantitative reverse
      transcription-polymerase chain reaction and their association with RB was
      assessed by statistical data analysis and receiver operating characteristic
      curves. Plasma miRNA (miR)-320, miR-let-7e and miR-21 levels were downregulated
      in the patient samples, the areas under the curves (AUCs) were 0.548-0.660,
      whereas the AUCs of combined classifiers were >=0.990. The plasma miRNA levels,
      particularly of miR-320, were found to be of value in RB diagnosis and may be
      considered as novel diagnostic biomarkers.

PMID- 24748988
TI  - Low follicular fluid tyrosine concentration in infertile women with ovarian
      hyperstimulation syndrome.
AB  - The aim of this study was to compare the branched-chain amino acid (BCAA) and
      tyrosine concentration in the follicular fluid of infertile women with and
      without ovarian hyperstimulation syndrome (OHSS) in an in vitro fertilization
      program combined with controlled ovarian stimulation. Follicular fluid was
      aspirated during oocyte retrieval from 20 infertile patients who developed
      moderate-to-severe OHSS and 20 age- and body mass index-matched normoresponders.
      BCAA and tyrosine concentration were measured using enzymatic methods. The
      follicular fluid BCAA concentration was similar between the two groups (P=0.55),
      whereas tyrosine concentration was significantly lower in the OHSS compared to
      that in the normoresponder group (P=0.027) and the BCAA/tyrosine ratio was
      significantly higher in the OHSS compared to that in the normoresponder group
      (P=0.034). These results suggest an association between low follicular fluid
      tyrosine concentration and OHSS. Dopamine receptor agonists may be used as
      potential anti-OHSS medicines and tyrosine, as a dopamine precursor, may play a
      role against the development of OHSS.

PMID- 24748989
TI  - Association of methionine synthase rs1801394 and methionine synthase reductase
      rs1805087 polymorphisms with meningioma in adults: A meta-analysis.
AB  - Several epidemiological studies suggested that methionine synthase (MTRR)
      rs1801394 and methionine synthase reductase (MTR) rs1805087 polymorphisms may be
      involved in the risk of meningioma in adults; however, the results from different
      case-control studies have been inconsistent. Therefore, we performed a meta
      analysis to investigate the association of MTRR and MTR polymorphisms with
      meningioma. PubMed, Web of Knowledge, China National Knowledge Infrastructure and
      Wanfang databases were searched up to October 30, 2013 and 3 publications,
      involving 7 case-control studies, were finally included. Following data
      extraction, a meta-analysis was conducted using Stata 12.0 software. The pooled
      results based on the fixed effects model demonstrated that the MTRR rs1801394
      polymorphism was associated with an increased risk of meningioma [odds ratio
      (OR)=1.18, 95% confidence interval (CI): 1.05-1.32 for G vs. A; OR=1.41, 95% CI:
      1.12-1.77 for GG vs. AA; OR=1.08, 95% CI: 0.94-1.33 for AG vs. AA; OR=1.19, 95%
      CI: 1.01-1.40 for (AG+GG) vs. AA; and OR=1.32, 95% CI: 1.07-1.63 for GG vs.
      (AG+AA)]; however, an association between the MTR rs1805087 polymorphism and the
      risk of meningioma was not identified [OR=0.99, 95% CI: 0.88-1.12 for G vs. A;
      OR=1.09, 95% CI: 0.80-1.48 for GG vs. AA; OR=0.95, 95% CI: 0.82-1.11 for AG vs.
      AA; OR=0.97, 95% CI: 0.84-1.13 for (AG+GG) vs. AA; and OR=1.09, 95% CI: 0.80-1.48
      for GG vs. (AG+AA)]. Therefore, the currently available evidence suggests that
      the MTRR rs1801394 polymorphism may increase the risk of meningioma, whereas the
      MTRR rs1801394 polymorphism is not associated with meningioma.

PMID- 24748990
TI  - Baicalin inhibits TLR7/MYD88 signaling pathway activation to suppress lung
      inflammation in mice infected with influenza A virus.
AB  - The present study aimed to investigate the protective effects and underlying
      mechanisms of baicalin on imprinting control region mice infected with influenza
      A/FM/1/47 (H1N1) virus. Oral administration of baicalin into mice infected with
      H1N1 prevented death, increased the mean time to death and inhibited lung index
      and lung consolidation. Subsequently, fluorescence quantitative polymerase chain
      reaction was used to assess the mRNA expression of toll-like receptor 7 (TLR7)
      and myeloid differentiation primary response gene 88 (MYD88), and western blot
      analysis was used to determine the expression of phosphorylated nuclear factor
      kappaB (NF-kappaB)-P65 and c-jun/activator protein 1 (AP-1). An enzyme-linked
      immunosorbent assay was applied to test for the inflammatory cytokines, tumor
      necrosis factor (TNF)-alpha and interleukin (IL)-1beta and IL-6, in the lung
      tissue. The findings indicated that baicalin downregulated the mRNA expression of
      TLR7 and MYD88, significantly downregulated the protein expression of NF-kappaB
      P65 and AP-1 and also inhibited the secretion of TNF-alpha, IL-1beta and IL-6. In
      conclusion, baicalin effectively reduced the pathological damage and inflammation
      of the lungs by downregulating the TLR7/MYD88-mediated signaling pathway.

PMID- 24748991
TI  - Superhydrophobic Surface Enhanced Raman Scattering Sensing using Janus Particle
      Arrays Realized by Site-Specific Electrochemical Growth.
AB  - Site-specific electrochemical deposition is used to prepare polystyrene (PS)-Ag
      Janus particle arrays with superhydrophobic properties. The analyte molecules can
      be significantly enriched using the superhydrophobic property of the PS-Ag Janus
      particle array before SERS detections, enabling an extremely sensitive detection
      of molecules in a highly diluted solution (e.g., femtomolar level). This
      superhydrophobic surface enhanced Raman scattering sensing concept described here
      is of critical significance in biosensing and bioanalysis. Most importantly, the
      site-specific electrochemical growth method we developed here is a versatile
      approach that can be used to prepare Janus particle arrays with different
      properties for various applications.

PMID- 24748992
TI  - Developing a Model of the Benefits and Burdens of Research Participation in
      Cancer Clinical Trials.
AB  - BACKGROUND: Recruiting and retaining human participants in cancer clinical trials
      is challenging for many investigators. Although we expect participants to
      identify and weigh the benefits and burdens of research participation for
      themselves, it is not clear what burdens adult cancer participants perceive in
      relation to benefits. We identify key attributes and develop an initial
      conceptual framework of benefit and burden based on interviews with individuals
      enrolled in cancer clinical research. METHODS: Semistructured interviews were
      conducted with a purposive sample of 32 patients enrolled in cancer clinical
      trials at a large northeastern cancer center. Krueger's guidelines for
      qualitative methodology were followed. RESULTS: Respondents reported a range of
      benefits and burdens associated with research participation. Benefits such as
      access to needed medications that subjects otherwise might not be able to afford,
      early detection and monitoring of the disease, potential for remission or cure,
      and the ability to take control of their lives through actively participating in
      the trial were identified. Burdens included the potentiality of side effects,
      worry and fear of the unknown, loss of job support, and financial concerns.
      CONCLUSIONS: Both benefit and burden influence research participation, including
      recruitment and retention in clinical trials. Dimensions of benefit and burden
      include physical, psychological, economic, familial, and social. Understanding
      the benefit-burden balance involved in the voluntary consent of human subjects is
      a fundamental tenet of research and important to ensure that subjects have made
      an informed decision regarding their decision to participate in clinical
      research.

PMID- 24748993
TI  - Plugfest 2009: Global Interoperability in Telerobotics and Telemedicine.
AB  - Despite the great diversity of teleoperator designs and applications, their
      underlying control systems have many similarities. These similarities can be
      exploited to enable inter-operability between heterogeneous systems. We have
      developed a network data specification, the Interoperable Telerobotics Protocol,
      that can be used for Internet based control of a wide range of teleoperators. In
      this work we test interoperable telerobotics on the global Internet, focusing on
      the telesurgery application domain. Fourteen globally dispersed telerobotic
      master and slave systems were connected in thirty trials in one twenty four hour
      period. Users performed common manipulation tasks to demonstrate effective master
      slave operation. With twenty eight (93%) successful, unique connections the
      results show a high potential for standardizing telerobotic operation.
      Furthermore, new paradigms for telesurgical operation and training are presented,
      including a networked surgery trainer and upper-limb exoskeleton control of micro
      manipulators.

PMID- 24748994
TI  - Implicit Active Constraints for Robot-Assisted Arthroscopy.
AB  - This paper presents an Implicit Active Constraints control framework for robot
      assisted minimally invasive surgery. It extends on current frameworks by
      prescribing the external constraints implicitly from the operator motion,
      forgoing the need for pre-operative imaging; the constraints are defined in situ
      so as to avoid the use of invasive fiducial markers. A hands-on cooperatively
      controlled robotic platform, comprising of a surgical instrument and a compliant
      manipulator, has been designed for an arthroscopic procedure. The surgical
      platform is capable of constraining the pose of the instrument so as to ensure it
      passes through the incision point and does not cause trauma to the surrounding
      tissue. A flexible arthroscopic instrument is designed and its use is
      investigated to enlarge reachable and dexterous workspace, increasing the
      accessibility to the target anatomy. The behaviour of the flexible instrument is
      analysed. A detailed performance analysis is conducted on a group of subjects for
      validating the control framework, simulating a minimally invasive arthroscopic
      procedure. Results demonstrate a statistically significant enhancement in the
      control ergonomics as well as the accuracy and safety of the procedure.

PMID- 24748995
TI  - Identifying design considerations for a shared decision aid for use at the point
      of outpatient clinical care: An ethnographic study at an inner city clinic.
AB  - BACKGROUND AND OBJECTIVE: Computerized decision aids could facilitate shared
      decision-making at the point of outpatient clinical care. The objective of this
      study was to investigate whether a computerized shared decision aid would be
      feasible to implement in an inner-city clinic by evaluating the current practices
      in shared decision-making, clinicians' use of computers, patient and clinicians'
      attitudes and beliefs toward computerized decision aids, and the influence of
      time on shared decision-making. METHODS: Qualitative data analysis of
      observations and semi-structured interviews with patients and clinicians at an
      inner-city outpatient clinic. FINDINGS: The findings provided an exploratory look
      at the prevalence of shared decision-making and attitudes about health
      information technology and decision aids. A prominent barrier to clinicians
      engaging in shared decision-making was a lack of perceived patient understanding
      of medical information. Some patients preferred their clinicians make
      recommendations for them rather than engage in formal shared decision-making.
      Health information technology was an integral part of the clinic visit and
      welcomed by most clinicians and patients. Some patients expressed the desire to
      engage with health information technology such as viewing their medical
      information on the computer screen with their clinicians. All participants were
      receptive to the idea of a decision aid integrated within the clinic visit
      although some clinicians were concerned about the accuracy of prognostic
      estimates for complex medical problems. IMPLICATIONS: We identified several
      important considerations for the design and implementation of a computerized
      decision aid including opportunities to: bridge clinician-patient communication
      about medical information while taking into account individual patients' decision
      making preferences, complement expert clinician judgment with prognostic
      estimates, take advantage of patient waiting times, and make tasks involved
      during the clinic visit more efficient. These findings should be incorporated
      into the design and implementation of a computerized shared decision aid at an
      inner-city hospital.

PMID- 24748996
TI  - Perceptually Docked Control Environment for Multiple Microbots: Application to
      the Gastric Wall Biopsy.
AB  - This paper presents a human-robot interface with perceptual docking to allow for
      the control of multiple microbots. The aim is to demonstrate that real-time eye
      tracking can be used for empowering robots with human vision by using knowledge
      acquired in situ. Several micro-robots can be directly controlled through a
      combination of manual and eye control. The novel control environment is
      demonstrated on a virtual biopsy of gastric lesion through an endoluminal
      approach. Twenty-one subjects were recruited to test the control environment.
      Statistical analysis was conducted on the completion time of the task using the
      keyboard control and the proposed eye tracking framework. System integration with
      the concept of perceptual docking framework demonstrated statistically
      significant improvement of task execution.

PMID- 24748997
TI  - A Hand-held Instrument for in vivo Probe-based Confocal Laser Endomicroscopy
      during Minimally Invasive Surgery.
AB  - Probe-based confocal laser endomicroscopy (pCLE) provides high resolution imaging
      of tissue in vivo. Maintaining a steady contact between target tissue and pCLE
      probe tip is important for image consistency. In this paper, a new prototype hand
      held instrument for in vivo pCLE during Minimally Invasive Surgery (MIS) is
      presented. The proposed instrument incorporates adaptive force sensing and
      actuation, allowing improved image consistency and force control, thus minimizing
      tissue deformation and induced micro-structural variations. The performance and
      accuracy of the contact force control are evaluated in detailed laboratory
      settings and in vivo validation of the device during transanal microsurgery in a
      live porcine model further demonstrates the potential clinical value of the
      device.

PMID- 24748998
TI  - Design of a Multitasking Robotic Platform with Flexible Arms and Articulated Head
      for Minimally Invasive Surgery.
AB  - This paper describes a multitasking robotic platform for Minimally Invasive
      Surgery (MIS). The device is designed to be introduced through a standard trocar
      port. Once the device is inserted to the desired surgical site, it can be
      reconfigured by lifting an articulated section, and protruding two tendon driven
      flexible arms. Each of the arms holds an interchangeable surgical instrument. The
      articulated section features a 2 Degrees-of-Freedom (DoF) universal joint
      followed by a single DoF yaw joint. It incorporates an on-board camera and LED
      light source at the distal end, leaving a O3mm channel for an additional
      instrument. The main shaft of the robot is largely hollow, leaving ample space
      for the insertion of two tendon driven flexible arms integrated with surgical
      instruments. The ex-vivo and in-vivo experiments demonstrate the potential
      clinical value of the device for performing surgical tasks through single
      incision or natural orifice transluminal procedures.

PMID- 24748999
TI  - Gaze Contingent Cartesian Control of a Robotic Arm for Laparoscopic Surgery.
AB  - This paper introduces a gaze contingent controlled robotic arm for laparoscopic
      surgery, based on gaze gestures. The method offers a natural and seamless
      communication channel between the surgeon and the robotic laparoscope. It offers
      several advantages in terms of reducing on-screen clutter and efficiently
      conveying visual intention. The proposed hands-free system enables the surgeon to
      be part of the robot control feedback loop, allowing user-friendly camera panning
      and zooming. The proposed platform avoids the limitations of using dwell-time
      camera control in previous gaze contingent camera control methods. The system
      represents a true hands-free setup without the need of obtrusive sensors mounted
      on the surgeon or the use of a foot pedal. Hidden Markov Models (HMMs) were used
      for real-time gaze gesture recognition. This method was evaluated with a cohort
      of 11 subjects by using the proposed system to complete a modified upper
      gastrointestinal staging laparoscopy and biopsy task on a phantom box trainer,
      with results demonstrating the potential clinical value of the proposed system.

PMID- 24749000
TI  - Evaluation of HemogloBindTM treatment for preparation of samples for
      cholinesterase analysis.
AB  - Acetylcholine is an essential neurotransmitter found throughout the nervous
      system. Its action on postsynaptic receptors is regulated through hydrolysis by
      various carboxylesterases, especially cholinesterases (ChEs). The acute toxicity
      of organophosphate (OP) compounds is directly linked to their action as
      inhibitors of ChE. One widely used assay for evaluating ChE activity is a
      spectrophotometric method developed by Ellman et al. When the enzyme source is
      from tissues or, in particular, blood, hemoglobin displays a spectrophotometric
      peak at the same wavelength used to analyze cholinergic activity. This creates a
      substantial background that interferes with the Ellman's assay and must be
      overcome in order to accurately monitor cholinesterase activity. Herein, we
      directly compare blood processing methods: classical method (1.67 +/- 0.30 U/mL)
      and HemogloBindTM treatment (1.51 +/- 0.17 U/mL), and clearly demonstrate that
      pretreatment of blood samples with HemoglobindTM is both a sufficient and rapid
      sample preparation method for the assessment of ChE activity using the Ellman's
      method.

PMID- 24749001
TI  - Improved image analysis of DETECHIP(r) allows for increased specificity in drug
      discrimination.
AB  - DETECHIP(r) is a novel molecular sensing array being developed for the detection
      and identification of a variety of compounds including controlled substances.
      This easy to use technology has the ability to produce a unique identifying
      binary code for each substance tested. Original analysis methodology relied on
      human vision to classify color and fluorescence changes within the array. New
      digital color image analysis techniques using red-green-blue (RGB) color values
      provided a higher degree of specificity and greater consistency. This image
      analysis technique was able to detect more subtle changes in color and was
      therefore able to properly discriminate between substances that previously
      produced identical codes. This technique was also expanded to analyze changes in
      RGB color values individually, increasing the length of the code to 48 digits and
      therefore potentially providing a further increase in specificity. To show the
      applicability of this new method, a blind study was performed, correctly
      identifying two unknown analytes.

PMID- 24749002
TI  - When Informationists Get Involved: the CHICA-GIS Project.
AB  - Child Health Improvement through Computer Automation (CHICA) is a computer
      decision support system (CDSS) that interfaces with existing electronic medical
      record systems (EMRS) and delivers "just-in-time" patient-relevant guidelines to
      physicians during the clinical encounter and accurately captures structured data
      from all who interact with the system. "Delivering Geospatial Intelligence to
      Health Care Professionals (CHICA-GIS)" (1R01LM010923-01) expands the medical
      application of Geographic Information Systems (GIS) by integrating a geographic
      information system with CHICA. To provide knowledge management support for CHICA
      GIS, three informationists at the Indiana University School of Medicine were
      awarded a supplement from the National Library Medicine. The informationists will
      enhance CHICA-GIS by: improving the accuracy and accessibility of information,
      managing and mapping the knowledge which undergirds the CHICA-GIS decision
      support tool, supporting community engagement and consumer health information
      outreach, and facilitating the dissemination of new CHICA-GIS research results
      and services.

PMID- 24749003
TI  - Effect of Surgical Technique on Corneal Implant Performance.
AB  - PURPOSE: Our aim was to determine the effect of a surgical technique on
      biomaterial implant performance, specifically graft retention. METHODS: Twelve
      mini pigs were implanted with cell-free, 1-ethyl-3-(3-dimethyl aminopropyl)
      carbodiimide (EDC)/N-hydroxysuccinimide (NHS) cross-linked recombinant human
      collagen type III (RHCIII) hydrogels as substitutes for donor corneal allografts
      using overlying sutures with or without human amniotic membrane (HAM) versus
      interrupted sutures with HAM. The effects of the retention method were compared
      as well as the effects of collagen concentration (13.7% to 15% RHCIII). RESULTS:
      All implanted corneas showed initial haze that cleared with time, resulting in
      corneas with optical clarity matching those of untreated controls. Biochemical
      analysis showed that by 12 months post operation, the initial RHCIII implants had
      been completely remodeled, as type I collagen, was the major collagenous protein
      detected, whereas no RHCIII could be detected. Histological analysis showed all
      implanted corneas exhibited regeneration of epithelial and stromal layers as well
      as nerves, along with touch sensitivity and tear production. Most
      neovascularization was seen in corneas stabilized by interrupted sutures.
      CONCLUSIONS: This showed that the surgical technique used does have a significant
      effect on the overall performance of corneal implants, overlying sutures caused
      less vascularization than interrupted sutures. TRANSLATIONAL RELEVANCE:
      Understanding the significance of the suturing technique can aid the selection of
      the most appropriate procedure when implanting artificial corneal substitutes.
      The same degree of regeneration, despite a higher collagen content indicates that
      future material development can progress toward stronger, more resistant
      implants.

PMID- 24749004
TI  - RAN GTPase and Osteopontin in Pancreatic Cancer.
AB  - INTRODUCTION: Pancreatic ductal adenocarcinoma (PDA) has the worst prognosis
      among cancers, mainly due to the high incidence of early metastases. RAN small
      GTPase (RAN) is a protein that plays physiological roles in the regulation of
      nuclear transport and microtubule spindle assembly. RAN was recently shown to
      mediate the invasive functions of the prometastatic protein osteopontin (OPN) in
      breast cancer cells. We and others have shown previously that high levels of OPN
      are present in PDA. In this study, we analyzed the expression and correlation of
      RAN with OPN in human pancreatic lesions, and explored their regulation in PDA
      cell lines. METHODS: Real time PCR was used to analyze RAN and OPN mRNA levels in
      PDA, adjacent non-malignant, and benign pancreatic tissues. Expression levels
      were correlated with survival and different clinicopathological parameters using
      different statistical methods. Transient transfection studies using OPN and RAN
      plasmids, and knockdown experiments using siRNA were used to examine their mutual
      regulation. RESULTS: OPN and RAN levels highly correlated with each other
      (p<0.0001). OPN or RAN levels did not correlate with venous lymphatic invasion,
      diabetes, obesity, T stage, BMI, or survival. However, we found a significant
      association between RAN levels and perineural invasion (HR=0.79, 95% CI 0.59,
      1.07; p=0.0378.). OPN and RAN colocalized in PDA tissues and cell lines.
      Increasing RAN expression in PDA cells induced OPN transcription and RAN
      silencing reduced total OPN levels. OPN did not have any significant effect on
      RAN transcription. CONCLUSIONS: The high levels of RAN in PDA and its correlation
      with OPN and with perineural invasion suggest that RAN may contribute to PDA
      metastasis and progression through the induction of OPN. RAN's role in the
      regulation of OPN in PDA is unique and could provide potential novel therapeutic
      strategies to combat PDA aggressiveness.

PMID- 24749005
TI  - Tumor vascular disruption using various radiation types.
AB  - The feasibility of disrupting a tumor's vascular structure with various radiation
      types and radionuclides is investigated. Calculated absorbed dose profiles for
      photons and (4)He ions suggest that low-energy beta-gamma and alpha emitting
      radionuclides can deposit sufficient absorbed dose to disrupt a tumor's vascular
      structure while minimizing the dose outside the blood vessel. Candidate
      radionuclides uniformly distributed in microspheres are theoretically
      investigated with respect to their vascular disruption potential and to offer an
      alternative to (90)Y microsphere therapy. Requisite activities of candidate low
      energy beta-gamma and alpha emitting radionuclides to facilitate vascular
      disruption are calculated. 

PMID- 24749006
TI  - Severity of chronic Lyme disease compared to other chronic conditions: a quality
      of life survey.
AB  - Overview. The Centers for Disease Control and Prevention (CDC) health-related
      quality of life (HRQoL) indicators are widely used in the general population to
      determine the burden of disease, identify health needs, and direct public health
      policy. These indicators also allow the burden of illness to be compared across
      different diseases. Although Lyme disease has recently been acknowledged as a
      major health threat in the USA with more than 300,000 new cases per year, no
      comprehensive assessment of the health burden of this tickborne disease is
      available. This study assesses the HRQoL of patients with chronic Lyme disease
      (CLD) and compares the severity of CLD to other chronic conditions. Methods. Of
      5,357 subjects who responded to an online survey, 3,090 were selected for the
      study. Respondents were characterized as having CLD if they were clinically
      diagnosed with Lyme disease and had persisting symptoms lasting more than 6
      months following antibiotic treatment. HRQoL of CLD patients was assessed using
      the CDC 9-item metric. The HRQoL analysis for CLD was compared to published
      analyses for the general population and other chronic illnesses using standard
      statistical methods. Results. Compared to the general population and patients
      with other chronic diseases reviewed here, patients with CLD reported
      significantly lower health quality status, more bad mental and physical health
      days, a significant symptom disease burden, and greater activity limitations.
      They also reported impairment in their ability to work, increased utilization of
      healthcare services, and greater out of pocket medical costs. Conclusions. CLD
      patients have significantly impaired HRQoL and greater healthcare utilization
      compared to the general population and patients with other chronic diseases. The
      heavy burden of illness associated with CLD highlights the need for earlier
      diagnosis and innovative treatment approaches that may reduce the burden of
      illness and concomitant costs posed by this illness. 

PMID- 24749007
TI  - Contribution of insect pollinators to crop yield and quality varies with
      agricultural intensification.
AB  - Background. Up to 75% of crop species benefit at least to some degree from animal
      pollination for fruit or seed set and yield. However, basic information on the
      level of pollinator dependence and pollinator contribution to yield is lacking
      for many crops. Even less is known about how insect pollination affects crop
      quality. Given that habitat loss and agricultural intensification are known to
      decrease pollinator richness and abundance, there is a need to assess the
      consequences for different components of crop production. Methods. We used
      pollination exclusion on flowers or inflorescences on a whole plant basis to
      assess the contribution of insect pollination to crop yield and quality in four
      flowering crops (spring oilseed rape, field bean, strawberry, and buckwheat)
      located in four regions of Europe. For each crop, we recorded abundance and
      species richness of flower visiting insects in ten fields located along a
      gradient from simple to heterogeneous landscapes. Results. Insect pollination
      enhanced average crop yield between 18 and 71% depending on the crop. Yield
      quality was also enhanced in most crops. For instance, oilseed rape had higher
      oil and lower chlorophyll contents when adequately pollinated, the proportion of
      empty seeds decreased in buckwheat, and strawberries' commercial grade improved;
      however, we did not find higher nitrogen content in open pollinated field beans.
      Complex landscapes had a higher overall species richness of wild pollinators
      across crops, but visitation rates were only higher in complex landscapes for
      some crops. On the contrary, the overall yield was consistently enhanced by
      higher visitation rates, but not by higher pollinator richness. Discussion. For
      the four crops in this study, there is clear benefit delivered by pollinators on
      yield quantity and/or quality, but it is not maximized under current agricultural
      intensification. Honeybees, the most abundant pollinator, might partially
      compensate the loss of wild pollinators in some areas, but our results suggest
      the need of landscape-scale actions to enhance wild pollinator populations. 

PMID- 24749008
TI  - Association between shell morphology of micro-land snails (genus Plectostoma) and
      their predator's predatory behaviour.
AB  - Predator-prey interactions are among the main ecological interactions that shape
      the diversity of biological form. In many cases, the evolution of the mollusc
      shell form is presumably driven by predation. However, the adaptive significance
      of several uncommon, yet striking, shell traits of land snails are still poorly
      known. These include the distorted coiled "tuba" and the protruded radial ribs
      that can be found in micro-landsnails of the genus Plectostoma. Here, we
      experimentally tested whether these shell traits may act as defensive adaptations
      against predators. We characterised and quantified the possible anti-predation
      behaviour and shell traits of Plectostoma snails both in terms of their
      properties and efficiencies in defending against the Atopos slug predatory
      strategies, namely, shell-apertural entry and shell-drilling. The results showed
      that Atopos slugs would first attack the snail by shell-apertural entry, and,
      should this fail, shift to the energetically more costly shell-drilling strategy.
      We found that the shell tuba of Plectostoma snails is an effective defensive
      trait against shell-apertural entry attack. None of the snail traits, such as
      resting behaviour, shell thickness, shell tuba shape, shell rib density and
      intensity can fully protect the snail from the slug's shell-drilling attack.
      However, these traits could increase the predation costs to the slug. Further
      analysis on the shell traits revealed that the lack of effectiveness in these
      anti-predation shell traits may be caused by a functional trade-off between shell
      traits under selection of two different predatory strategies. 

PMID- 24749009
TI  - Intuitive physics and intuitive psychology ("theory of mind") in offspring of
      mothers with psychoses.
AB  - Offspring of individuals with psychoses sometimes display an abnormal development
      of cognition, language, motor performance, social adaptation, and emotional
      functions. The aim of this study was to investigate the ability of children of
      mothers with schizophrenia (n = 28) and bipolar disorder (n = 23) to understand
      mental states of others using the Eyes Test (folk psychology or "theory of mind")
      and physical causal interactions of inanimate objects (folk physics). Compared
      with healthy controls (n = 29), the children of mothers with schizophrenia
      displayed significantly impaired performances on the Eyes Test but not on the
      folk physics test when corrected for IQ. The children of mothers with bipolar
      disorder did not differ from the controls. The folk physics test showed a
      significant covariance with IQ, whereas the Eyes Test did not exhibit such
      covariance. These results suggest that the attribution of mental states, but not
      the interpretation of causal interaction of objects, is impaired in offspring of
      individuals with schizophrenia, which may contribute to social dysfunctions. 

PMID- 24749010
TI  - Regular group exercise is associated with improved mood but not quality of life
      following stroke.
AB  - Purpose. People with stroke living in the community have an increased prevalence
      of depression and lower quality of life than healthy older adults. This cross
      sectional observational study investigated whether participation in regular
      exercise was associated with improved mood and quality of life. Methods. We
      recruited three groups of community dwelling participants: 13 healthy older
      adults, 17 adults post-stroke who regularly participated in group exercise at a
      community fitness facility and 10 adults post-stroke who did not regularly
      exercise. We measured mood using the Depression, Anxiety, Stress Scale (DASS) and
      quality of life using the Assessment of Quality of Life (AQoL) scale. Results.
      Levels of stress and depression were significantly greater in the people with
      stroke who did not undertake regular exercise (p = 0.004 and p = 0.004
      respectively), although this group had more recent strokes (p < 0.001). Both
      stroke groups had lower quality of life scores (p = 0.04) than the healthy
      adults. Conclusions. This small, community-based study confirms that people
      following stroke report poorer quality of life than stroke-free individuals.
      However, those who exercise regularly have significantly lower stress and
      depression compared to stroke survivors who do not. Future research should focus
      on the precise type and amount of exercise capable of improving mood following
      stroke. 

PMID- 24749011
TI  - The large-scale blast score ratio (LS-BSR) pipeline: a method to rapidly compare
      genetic content between bacterial genomes.
AB  - Background. As whole genome sequence data from bacterial isolates becomes cheaper
      to generate, computational methods are needed to correlate sequence data with
      biological observations. Here we present the large-scale BLAST score ratio (LS
      BSR) pipeline, which rapidly compares the genetic content of hundreds to
      thousands of bacterial genomes, and returns a matrix that describes the
      relatedness of all coding sequences (CDSs) in all genomes surveyed. This matrix
      can be easily parsed in order to identify genetic relationships between bacterial
      genomes. Although pipelines have been published that group peptides by sequence
      similarity, no other software performs the rapid, large-scale, full-genome
      comparative analyses carried out by LS-BSR. Results. To demonstrate the utility
      of the method, the LS-BSR pipeline was tested on 96 Escherichia coli and Shigella
      genomes; the pipeline ran in 163 min using 16 processors, which is a greater than
      7-fold speedup compared to using a single processor. The BSR values for each CDS,
      which indicate a relative level of relatedness, were then mapped to each genome
      on an independent core genome single nucleotide polymorphism (SNP) based
      phylogeny. Comparisons were then used to identify clade specific CDS markers and
      validate the LS-BSR pipeline based on molecular markers that delineate between
      classical E. coli pathogenic variant (pathovar) designations. Scalability tests
      demonstrated that the LS-BSR pipeline can process 1,000 E. coli genomes in 27-57
      h, depending upon the alignment method, using 16 processors. Conclusions. LS-BSR
      is an open-source, parallel implementation of the BSR algorithm, enabling rapid
      comparison of the genetic content of large numbers of genomes. The results of the
      pipeline can be used to identify specific markers between user-defined
      phylogenetic groups, and to identify the loss and/or acquisition of genetic
      information between bacterial isolates. Taxa-specific genetic markers can then be
      translated into clinical diagnostics, or can be used to identify broadly
      conserved putative therapeutic candidates. 

PMID- 24749012
TI  - Predicting changes in language skills between 2 and 3 years in the EDEN mother
      child cohort.
AB  - Objective. To examine the factors predicting changes in language skills between 2
      and 3 years. Methods. By using longitudinal data concerning 1002 children from
      the EDEN study, linear regression was used to predict 3-year language performance
      from 2-year language performance and the risk factors associated with language
      delays. Logistic regressions were performed to examine two change trajectories:
      children who fall below the 10th percentile of language skills between 2 and 3
      years (declining trajectory), and those who rose above the 10th percentile
      (resilient trajectory). Results. The final linear model accounted for 43% of the
      variance in 3-year language scores, with 2-year language scores accounting for
      22%. Exposure to alcohol during pregnancy, earlier birth term, lower level of
      parental education and lower frequency of maternal stimulation were associated
      with the declining trajectory. Breastfeeding was associated with the resilient
      trajectory. Conclusions. This study provides a better understanding of the
      natural history of early language delays by identifying biological and social
      factors that predict changes in language skills between the ages of 2 and 3
      years. 

PMID- 24749013
TI  - Fibrinogen - a possible extracellular target for inositol phosphates.
AB  - A potential extracellular target for inositol phosphates and analogues with
      anticancer properties is identified. Proteins from detergent-solubilised HeLa
      cell lysates bound to a novel affinity column of myo-inositol 1,3,4,5,6
      pentakisphosphate (InsP5) coupled to Affigel-10. One high-affinity ligand was
      fibrinogen Bbeta. Inositol phosphates and analogues were able to elute purified
      fibrinogen from this matrix. InsP5 and the inositol phosphate mimic biphenyl
      2,3',4,5',6-pentakisphosphate (BiPhP5) bind fibrinogen in vitro, and block the
      effects of fibrinogen in A549 cell-based assays of proliferation and migration.
      They are also able to prevent the fibrinogen-mediated activation of
      phosphatidylinositol 3-kinase. These effects of fibrinogen appear to be mediated
      through the intercellular adhesion molecule-1 (ICAM-1), as cells not expressing
      ICAM-1 fail to respond. In contrast, myo-inositol hexakisphosphate and the
      epimeric scyllo-inositol 1,2,3,4,5-pentakisphosphate were without effect. These
      findings are consistent with earlier reports that higher inositol phosphates have
      anticancer properties. This new mechanism of action and target for these
      extracellular inositol phosphates to have their effects allows a re-evaluation of
      earlier data.

PMID- 24749014
TI  - Multivalent benzene polyphosphate derivatives are non-Ca2+-mobilizing
      Ins(1,4,5)P3 receptor antagonists.
AB  - Inositol 1,4,5-trisphosphate [Ins(1,4,5)P31] mobilizes intracellular Ca2+ through
      the Ins(1,4,5)P3 receptor [InsP3R]. Although some progress has been made in the
      design of synthetic InsP3R partial agonists and antagonists, there are still few
      examples of useful small molecule competitive antagonists. A "multivalent"
      approach is explored and new dimeric polyphosphorylated aromatic derivatives were
      designed, synthesized and biologically evaluated. The established weak InsP3R
      ligand benzene 1,2,4-trisphosphate [Bz(1,2,4)P32] is dimerized through its 5
      position in two different ways, first directly as the biphenyl derivative
      biphenyl 2,2',4,4',5,5'-hexakisphosphate, [BiPh(2,2',4,4',5,5')P68] and with its
      regioisomeric biphenyl 3,3',4,4',5,5'-hexakisphosphate
      [BiPh(3,3',4,4',5,5')P611]. Secondly, a linker motif is introduced in a flexible
      ethylene-bridged dimer (9) with its corresponding 1,2-bisphosphate dimer (10),
      both loosely analogous to the very weak antagonist 1,2-bis(2-aminophenoxy)ethane
      N,N,N',N'-tetraacetic acid (BAPTA 7). In permeabilized L15 fibroblasts
      overexpressing type 1 InsP3R, BiPh(2,2',4,4',5,5')P6 (8) inhibits Ins(1,4,5)P3
      induced Ca2+ release in a apparently competitive fashion [IC50 187 nM] and the
      Bz(1,2,4)P3 dimer (9) is only slightly weaker [IC50 380 nM]. Compounds were also
      evaluated against type I Ins(1,4,5)P3 5-phosphatase. All compounds are resistant
      to dephosphorylation, with BiPh(2,2',4,4',5,5')P6 (8), being the most effective
      inhibitor of any biphenyl derivative synthesized to date [IC50 480 nM] and the
      Bz(1,2,4)P3 ethylene dimer (9) weaker [IC50 3.55 MUM]. BiPh(3,3',4,4',5,5')P6
      (11) also inhibits 5-phosphatase [IC50 730 nM] and exhibits unexpected Ca2+
      releasing activity [EC50 800 nM]. Thus, relocation of only a single mirrored
      phenyl phosphate group in (11) from that of antagonist (8) does not markedly
      change enzyme inhibitory activity, but elicits a dramatic switch in Ca2+
      releasing activity. Such new agents demonstrate the power of the multivalent
      approach and may be useful to investigate the chemical biology of signaling
      through InsP3R and as templates for further design.

PMID- 24749016
TI  - TriLink: Anatomic Double-Bundle Anterior Cruciate Ligament Reconstruction.
AB  - Cadaveric and clinical biomechanical studies show improved kinematic restoration
      using double-bundle anterior cruciate ligament (ACL) reconstruction techniques.
      These have been criticized in the past for being technically challenging. We
      present a novel 3-socket approach for anatomic "all-inside" double-bundle
      reconstruction using a single hamstring tendon fashioned to create a trifurcate
      graft: the TriLink technique. The semitendinosus alone is harvested, quadrupled,
      and attached to 3 suspensory fixation devices in a Y-shaped configuration,
      creating a 4-stranded tibial limb and 2 double-stranded femoral limbs. A medial
      viewing/lateral working arthroscopic approach is adopted using specifically
      designed instrumentation. Anatomic placement of the 2 femoral tunnels is
      performed by a validated direct measurement technique. A single mid-bundle
      position is used on the tibia. Both femoral and tibial sockets are created in a
      retrograde manner using outside-to-in drilling. This is a simplified operative
      technique for anatomic double-bundle ACL reconstruction that maximizes bone
      preservation. The TriLink construct replicates the 2 bundles of the ACL,
      conferring native functional anisometry and improving femoral footprint coverage
      while avoiding the complexities and pitfalls of double-tibial tunnel techniques.
      Preservation of the gracilis reduces the morbidity of hamstring harvest and
      allows greater flexibility in graft choice in cases requiring multiligament
      reconstruction. 

PMID- 24749017
TI  - Arthroscopic femoral neck osteoplasty in the treatment of femoroacetabular
      impingement.
AB  - Femoral neck osteoplasty is an integral component for successful treatment of
      femoroacetabular impingement. Current techniques allow this to be performed
      arthroscopically, and results are equivalent to those of open procedures when
      typical anterior and anterosuperior lesions are considered. The arthroscopic
      procedure is dependent on obtaining adequate visualization through capsular
      management and proper leg positioning, and it requires fluoroscopy to guide and
      verify an adequate resection. We present our preferred technique for arthroscopic
      femoral neck osteoplasty. 

PMID- 24749018
TI  - Arthroscopic capsular repair in the treatment of femoroacetabular impingement.
AB  - The role of capsular repair in the arthroscopic treatment of femoroacetabular
      impingement remains poorly defined. Some surgeons rarely repair the capsule,
      whereas others perform repairs routinely. There is little direct clinical
      evidence to guide surgeon decision making. When capsular repairs are performed,
      the procedure requires adequate visualization and careful suture placement either
      to re-establish the patient's normal capsular volume or to plicate a redundant
      capsule in a hip with hyperlaxity preoperatively. We present our preferred
      technique for arthroscopic capsular repair. 

PMID- 24749019
TI  - Arthroscopic osteosynthesis of femoral head malunion.
AB  - We present the case of a femoral head malunion with lateral cephalic
      femoroacetabular impingement managed by arthroscopic osteotomy/takedown, bone
      grafting, internal fixation, and cephaloplasty. The treatment rationale and
      surgical technique are presented. A successful outcome at 3 years was obtained
      with radiographic evidence of union without osteonecrosis. Even beyond acute
      femoral head osteosynthesis, arthroscopic surgery may enhance the ability to
      treat femoral head malunions. Moreover, arthroscopic osteosynthesis may address
      lateral cephalic FAI, a previously unreported condition. 

PMID- 24749015
TI  - Cyclic ADP-Ribose and NAADP in Vascular Regulation and Diseases.
AB  - Cyclic ADP-ribose (cADPR) and nicotinic acid adenine dinucleotide phosphate
      (NAADP), two intracellular Ca2+ mobilizing second messengers, have been
      recognized as a fundamental signaling mechanism regulating a variety of cell or
      organ functions in different biological systems. Here we reviewed the literature
      regarding these ADP-ribosylcyclase products in vascular cells with a major focus
      on their production, physiological roles, and related underlying mechanisms
      mediating their actions. In particular, several hot topics in this area of
      research are comprehensively discussed, which may help understand some of the
      controversial evidence provided by different studies. For example, some new
      models are emerging for the agonist receptor coupling of CD38 or ADP
      ribosylcyclase and for the formation of an acidic microenvironment to facilitate
      the production of NAADP in vascular cells. We also summarized the evidence
      regarding the NAADP-mediated two-phase Ca2+ release with a slow Ca2+-induced Ca2+
      release (CICR) and corresponding physiological relevance. The possibility of a
      permanent structural space between lysosomes and sarcoplasmic reticulum (SR), as
      well as the critical role of lysosome trafficking in phase 2 Ca2+ release in
      response to some agonists are also explored. With respect to the molecular
      targets of NAADP within cells, several possible candidates including SR ryanodine
      receptors (RyRs), lysosomal transient receptor potential-mucolipin 1 (TRP-ML1)
      and two pore channels (TPCs) are presented with supporting and opposing evidence.
      Finally, the possible role of NAADP-mediated regulation of lysosome function in
      autophagy and atherogenesis is discussed, which may indicate a new direction for
      further studies on the pathological roles of cADPR and NAADP in the vascular
      system.

PMID- 24749020
TI  - Isolated arthroscopic rotator interval closure for shoulder instability.
AB  - We present our technique for isolated arthroscopic rotator interval closure in
      the treatment of mild symptomatic glenohumeral instability in the absence of a
      labral tear. A careful history, physical examination, and imaging help to
      identify a select subset of atraumatic instability patients who may benefit from
      this procedure, and diagnostic arthroscopy can provide further evidence. By use
      of a posterior viewing portal with anterior and anterolateral working portals,
      the anterior capsuloligamentous complex is mobilized, and the rotator interval is
      closed with carefully placed sutures to advance the capsule superiorly and
      provide tension through decreased capsular volume. 

PMID- 24749021
TI  - Endoscopic resection of a talocalcaneal coalition using a posteromedial approach.
AB  - Resection is a standard surgical procedure for a talocalcaneal coalition (TCC). A
      posterior approach is the representative technique for hindfoot endoscopy, and
      there is only 1 report of endoscopic resection of TCC using this approach.
      Disadvantages of the posterior approach for TCC are as follows: (1) the
      indication is limited to posterior-facet coalition, (2) the flexor hallucis
      longus can be an obstacle in approaching the coalition, (3) the acute insertion
      angle between the endoscope and instrument reduces operability, and (4) a
      position change and additional skin incision are essential for conversion to an
      open procedure. In contrast, a posteromedial approach for TCC with established
      portals at the entrance and exit of the flexor retinaculum is a useful technique
      because (1) the indication is allow to middle- and posterior-facet coalitions,
      (2) increased perfusion pressure allows the creation of sufficient working space,
      (3) operating the instrument only at the coalition site decreases the risk of
      tendon injury and neurovascular damage, (4) the obtuse insertion angle between
      the endoscope and instrument improves operability, and (5) a position change and
      additional skin incision are unnecessary for conversion to an open procedure. 

PMID- 24749022
TI  - Arthroscopic absorbable suture fixation for tibial spine fractures.
AB  - The purpose of this technical note and accompanying video is to describe a
      modified arthroscopic suture fixation technique to treat tibial spine avulsion
      fractures. Twenty-one patients underwent arthroscopic treatment for tibial spine
      avulsion with our technique; they were clinically and biomechanically evaluated
      at 2 years' follow-up and showed optimal clinical and radiographic outcomes.
      Repair with this arthroscopic technique provides a significant advantage in the
      treatment of type III and IV fractures of the tibial eminence by obtaining
      arthroscopic fixation within the substance of the anterior cruciate ligament:
      suture methods based on the avulsed bone fragment are technically impossible, but
      sutures through the base of the ligament itself provide secure fixation, reducing
      the risks of comminution of the fracture fragment and eliminating the time for
      hardware removal. This arthroscopic technique restores the length and the
      integrity of the anterior cruciate ligament and provides a simplified,
      reproducible method of treating patients, including young patients, with low
      hardware costs in comparison to sutures using anchors or other hardware. 

PMID- 24749024
TI  - Arthroscopic transfer of the pectoralis major for irreparable tear of the
      subscapularis: a preliminary report.
AB  - An irreparable tear of the subscapularis is a surgical challenge. Open approaches
      have been widely described to restore the anatomy and the function of the
      shoulder. Pectoralis major transfer is the most common technique used in this
      difficult clinical situation. Although this procedure has only been performed
      through an open approach, we describe a new arthroscopic technique for pectoralis
      major transfer. The critical part in this technique, in general, is the
      musculocutaneous nerve dissection, which is also possible through the
      arthroscopic approach. Together with an alternative method of harvesting using
      chips of bone and a minimal skin incision, this promising, less invasive
      technique presents all the advantages of the arthroscopic approach and provides a
      strong fixation to the lesser tuberosity. 

PMID- 24749023
TI  - Anatomic double-bundle anterior cruciate ligament reconstruction using in situ
      hamstring graft with 4 tunnels.
AB  - A careful review of the literature suggests that a significant number of patients
      undergoing anterior cruciate ligament (ACL) reconstruction have less-than-optimal
      results. Although overall outcomes of ACL reconstruction are favorable, there
      remains considerable room for improvement. Anatomically, the ACL consists of 2
      major functional bundles, the anteromedial bundle and the posterolateral bundle.
      Biomechanically, both bundles contribute significantly to the anterior and
      rotational stability of the knee. Therefore anatomic double-bundle ACL
      reconstruction techniques may further improve the outcomes in ACL surgery. This
      article presents a technique for arthroscopic double-bundle ACL reconstruction
      that includes the use of 2 femoral and 2 tibial tunnels to restore both the
      anteromedial and posterolateral bundles of the ACL with minimal hardware for
      fixation. 

PMID- 24749025
TI  - Arthroscopic-assisted core decompression for osteonecrosis of the femoral head.
AB  - The management of pre-collapse osteonecrosis of the femoral head is
      controversial. Core decompression is a technique that theoretically decreases the
      intraosseous pressure of the femoral head, resulting in a local vascularized
      healing response. Its efficacy has been shown in delaying early subchondral
      collapse. We describe the technique of arthroscopic-assisted core decompression
      of the femoral head for osteonecrosis. The advantages of this technique include
      evaluation of the presence or absence of articular cartilage injury, subchondral
      collapse, and guidance during reaming and curettage. It also allows the ability
      to address any concomitant soft-tissue or bony pathology associated with or in
      addition to the osteonecrotic lesion. 

PMID- 24749026
TI  - Hip arthroscopy: less invasive technique.
AB  - The popularity of hip arthroscopy has increased significantly over the past
      decade. It is technically demanding and may be associated with complications such
      as iatrogenic damage to the articular cartilage or acetabular labrum, compression
      injuries to the structures in the perineum, and distraction injuries to the leg.
      Some of these complications can be avoided by paying meticulous attention to the
      technique and reducing the traction/surgical time. We describe a technique by
      which the risk of injury to the articular cartilage may be minimized by
      introduction of the surgical instruments under direct vision, rather than under
      radiologic control. The described technique is likely to reduce the operating
      time by addressing the peripheral-compartment pathologies first-without traction.
      Traction is only required for the central-compartment procedures. Exposure to
      ionizing radiation is also diminished (eliminated with practice) because the
      portals are established under direct vision of the arthroscopist. 

PMID- 24749027
TI  - Peroneal tenodesis with the use of tendoscopy: surgical technique and report of 1
      case.
AB  - Peroneus brevis tendon injury is the most common lesion of the peroneal tendons.
      The initial treatment is conservative, and surgical treatment is indicated if
      conservative treatment fails. It is often necessary to open the entire upper and
      lower retinaculum to obtain adequate visualization of the structures. We present
      a case in which the peroneus brevis tenodesis was used with the aid of
      tendoscopy. This technique should be used for patients with lesions affecting
      more than 50% of the tendon diameter. We found that, by making small incisions,
      the patient recovered well, quickly, with resolution of pain. 

PMID- 24749028
TI  - Unusual appearance of an osteochondral lesion accompanying medial meniscus
      injury.
AB  - An osteochondral lesion in the knee joint is caused by a focal traumatic
      osteochondral defect, osteochondritis dissecans, an isolated degenerative lesion,
      or diffuse degenerative disease. An osteochondral lesion with a cleft-like
      appearance accompanying medial meniscus injury is rare without trauma. We report
      the case of a 13-year-old boy who complained of right knee pain and swelling,
      with radiographic findings of an osteochondral defect. Arthroscopic inspection
      showed an osteochondral lesion in the medial condyle of the femur and tibial
      plateau accompanying a partial medial meniscus discoid tear. Partial meniscectomy
      was performed, and a microfracture procedure was carried out on the osteochondral
      defect. The patient was asymptomatic at 2 years' follow-up. This technique is a
      relatively easy, completely arthroscopic procedure that spares the bone and
      cartilage and has yielded a good clinical outcome in a skeletally immature
      patient who had an osteochondral lesion with a cleft-like appearance. 

PMID- 24749029
TI  - Medial patellofemoral ligament reconstruction: a new technique for graft fixation
      at the patella without implants.
AB  - Patellofemoral instability is a complex disorder that is often accompanied by
      insufficiency or tearing of the medial patellofemoral ligament. Over the past few
      years, several techniques using free tendon grafts for medial patellofemoral
      ligament reconstruction have become popular because of their reproducible effect
      and good outcome. Whereas most surgeons prefer femoral fixation of the graft
      using an interference screw, the possibilities of patellar fixation are numerous.
      All of the different techniques have their own advantages and pitfalls. We
      describe a technique in which we drill 2 blind-ending tunnels (1 cm) at the
      medial aspect of the patella, where the doubled graft (not the free ends) is
      pulled in and fixed. By using a special technique for shuttling the sutures,
      there is no need for an additional skin incision and no need for implants,
      allowing very secure graft fixation without a relevant risk of fracture. 

PMID- 24749030
TI  - The "flying swan" technique: a novel method for anterior labral repair using a
      tensioned suture bridge.
AB  - Arthroscopic labral repair is an effective technique for most cases of traumatic
      shoulder instability. However, patients with anterior labroligamentous periosteal
      sleeve avulsion lesions frequently have multiple episodes of subluxation or
      dislocation and a high recurrence rate after surgery, even with modern methods of
      labral repair. One reason may be failure of biological healing of the labrum due
      to an inadequate "footprint" of contact between the capsulolabral tissue and the
      glenoid bone. We have developed a technique that facilitates a tensioned suture
      bridge between suture anchors that may improve the results of labral repair in
      patients with anterior labroligamentous periosteal sleeve avulsion lesions. 

PMID- 24749031
TI  - Arthroscopic wafer procedure for ulnar impaction syndrome.
AB  - Ulnar impaction syndrome is abutment of the ulna on the lunate and triquetrum
      that increases stress and load, causing ulnar-sided wrist pain. Typically, ulnar
      positive or -neutral variance is seen on a posteroanterior radiograph of the
      wrist. The management of ulnar impaction syndrome varies from conservative,
      symptomatic treatment to open procedures to shorten the ulna. Arthroscopic
      management has become increasingly popular for management of ulnar impaction with
      ulnar-positive variance of less than 3 mm and concomitant central triangular
      fibrocartilage complex tears. This method avoids complications associated with
      open procedures, such as nonunion and symptomatic hardware. The arthroscopic
      wafer procedure involves debridement of the central triangular fibrocartilage
      complex tear, along with debridement of the distal pole of the ulna causing the
      impaction. Debridement of the ulna arthroscopically is taken down to a level at
      which the patient is ulnar neutral or slightly ulnar negative. Previous studies
      have shown good results with relief of patient symptoms while avoiding
      complications seen with open procedures. 

PMID- 24749032
TI  - Endoscopic transtendinous repair for partial-thickness proximal hamstring tendon
      tears.
AB  - Partial tears of the proximal hamstring tendon can successfully be managed with
      tendon repair in cases of failed conservative management. As in partial-thickness
      gluteus medius repair, a transtendinous technique can be used to repair partial
      thickness undersurface tears of the hamstring origin. This report details an
      endoscopic transtendinous approach for the treatment of partial-thickness
      hamstring tendon tears. 

PMID- 24749033
TI  - Arthroscopic labralization of the hip: an alternative to labral reconstruction.
AB  - Labralization, which may be performed by open or arthroscopic means, may be an
      attractive alternative to hip labral reconstruction. By preserving the articular
      cartilage in the region of labral deficit with meticulous rim trimming, the
      resultant undermined free chondral margin ("pseudolabrum") may immediately
      restore a fluid seal function and may theoretically enhance hip preservation.
      Arthroscopic hip labralization is a relatively simple and fast procedure without
      graft harvest morbidity. It may be performed in patients tolerating rim reduction
      with encouraging preliminary outcomes. 

PMID- 24749034
TI  - Arthroscopic lateral epicondylitis release using the "bayonet" technique.
AB  - Most patients diagnosed with lateral epicondylitis respond well to conservative
      management. For patients who do not respond to nonoperative modalities, surgical
      treatment represents a viable option for long-term symptomatic relief. The
      arthroscopic surgical technique described in this article has been consistently
      used by the senior author for the treatment of recalcitrant lateral epicondylitis
      for more than 5 years (198 patients) without the occurrence of any major
      complications and appears to be a safe, reliable, and efficacious surgical
      intervention for the management of lateral epicondylitis. 

PMID- 24749035
TI  - Dry arthroscopy with a retraction system for matrix-aided cartilage repair of
      patellar lesions.
AB  - Several commercially available cartilage repair techniques use a natural or
      synthetic matrix to aid cartilage regeneration (e.g., autologous matrix-induced
      chondrogenesis or matrix-induced cartilage implantation). However, the use of
      matrix-aided techniques during conventional knee joint arthroscopy under
      continuous irrigation is challenging. Insertion and fixation of the matrix can be
      complicated by the presence of fluid and the confined patellofemoral joint space
      with limited access to the lesion. To overcome these issues, we developed a novel
      arthroscopic approach for matrix-aided cartilage repair of patellar lesions. This
      technical note describes the use of dry arthroscopy assisted by a minimally
      invasive retraction system. An autologous matrix-induced chondrogenesis procedure
      is used to illustrate this novel approach. 

PMID- 24749036
TI  - Hip arthroscopy for excision of osteoid osteoma of femoral neck.
AB  - Osteoid osteoma (OO) is the most commonly seen benign bone-forming lesion. It can
      occur anywhere, including the metaphyseal regions of small and large bones. We
      present 2 cases that underwent an arthroscopic technique for removal of OO of the
      femoral neck. The diagnosis was confirmed by computed tomography in addition to
      magnetic resonance imaging. The lesions were accessed arthroscopically and
      excised by unroofing and curettage. The clinical and radiographic findings are
      presented, along with the surgical management. The patients improved dramatically
      postoperatively. OO of the femoral neck should be included in the differential
      diagnosis of hip pain in young patients. Arthroscopic excision and curettage
      provide a good choice for management, with low morbidity and rapid recovery. 

PMID- 24749037
TI  - Arthroscopic repair of "peel-off" lesion of the posterior cruciate ligament at
      the femoral condyle.
AB  - Posterior cruciate ligament (PCL) injuries are uncommon, and most occur in
      association with other lesions. The treatment of PCL injuries remains
      controversial; in addition, PCL injuries have been documented to have a
      propensity to heal. In the literature several different patterns of PCL injury
      have been described including midsubstance tears/injuries, tibial bony avulsions,
      femoral bony avulsions, and femoral "peel-off" injuries. A peel-off injury is a
      complete or incomplete soft-tissue disruption of the PCL at its femoral
      attachment site without associated bony avulsion. In recent years arthroscopic
      repair of femoral avulsion and peel-off lesions of the PCL has been reported. In
      most of these articles, a transosseous repair with sutures passed through 2 bone
      tunnels into the medial femoral condyle has been described. We present a case of
      a femoral PCL avulsion in a 20-year-old collegiate football player with an
      associated medial collateral ligament injury, and we report about a novel
      technique for PCL repair using 2 No. 2 FiberWire sutures and two 2.9-mm PushLock
      anchors (Arthrex) to secure tensioning the ligament at its footprint. 

PMID- 24749038
TI  - Management of incarcerating pincer-type femoroacetabular impingement with hip
      arthroscopy.
AB  - This report describes the arthroscopic management of a case of incarcerating
      pincer-type femoroacetabular impingement. The hip joint had a marked restriction
      of range of motion and secondary pain as a result of osteophytes wrapping around
      the femoral head down the femoral neck. The patient was treated with staged
      bilateral hip arthroscopy. The procedures were initially performed through the
      peripheral compartment to remove the incarcerating acetabular rim, followed by
      arthroscopy of the central compartment with acetabuloplasty and femoral head
      osteochondroplasty. The patient's treatment has led to an excellent clinical and
      radiographic result at 24 months' follow-up despite an unrelated pelvic fracture
      sustained in the postoperative period. This technique emphasizes the capabilities
      of hip arthroscopy in advanced cases of femoroacetabular impingement as an
      alternative to arthroplasty for patients with healthy articular cartilage. 

PMID- 24749039
TI  - Arthroscopic Posterior Stabilization of the Shoulder Using a Percutaneous
      Knotless Mattress Suture Technique.
AB  - Posterior shoulder instability is far less common than anterior instability, and
      its arthroscopic treatment can be technically demanding. We describe a
      percutaneous arthroscopic technique for posterior shoulder stabilization using
      mattress sutures and knotless anchors. Spinal needles are used to pass the
      sutures percutaneously in a mattress fashion. Knotless anchors are used to secure
      the sutures under the labrum. These anchors can be used without cannulas, giving
      easier access to the posterior glenoid. This procedure is simple, cost-effective,
      and safe, avoiding the presence of both knots and suture strands in contact with
      the humeral head. 

PMID- 24749040
TI  - Arthroscopic sternoclavicular joint resection arthroplasty: a technical note and
      illustrated case report.
AB  - Open resection arthroplasty of the sternoclavicular (SC) joint has historically
      provided good long-term results in patients with symptomatic osteoarthritis of
      the SC joint. However, the procedure is rarely performed because of the risk of
      injury to vital mediastinal structures and concern regarding postoperative joint
      instability. Arthroscopic decompression of the SC joint has therefore emerged as
      a potential treatment option because of many recognized advantages including
      minimal tissue dissection, maintenance of joint stability, avoidance of posterior
      SC joint dissection, expeditious recovery, and improved cosmesis. There are,
      however, safety concerns given the proximity of neurovascular structures. In this
      article we demonstrate a technique for arthroscopic SC joint resection
      arthroplasty in a 26-year-old active man with bilateral, painful, idiopathic
      degenerative SC joint osteoarthritis. This case also highlights the pearls and
      pitfalls of arthroscopic resection arthroplasty for the SC joint. There were no
      perioperative complications. Four months postoperatively, the patient had
      returned to full activities, including weightlifting, without pain or evidence of
      SC joint instability. One year postoperatively, the patient showed substantial
      improvements in the American Shoulder and Elbow Surgeons score; Single Assessment
      Numeric Evaluation score; Quick Disabilities of the Arm, Shoulder and Hand score;
      and Short Form 12 Physical Component Summary score over preoperative baseline
      values. 

PMID- 24749041
TI  - Creation of an anatomic femoral tunnel with minimal damage to the remnant bundle
      in remnant-preserving anterior cruciate ligament reconstruction using an outside
      in technique.
AB  - We established a method for creation of an anatomic femoral tunnel with minimal
      damage to the remnant bundle in remnant-preserving anterior cruciate ligament
      (ACL) reconstruction. The goals of this surgical technique were to preserve the
      remnant bundle as much as possible, especially at the femoral insertion, and to
      make the tunnel at the anatomic position. The critical points are that the
      posterior side of the femoral footprint of the ACL is observed through the
      posterolateral portal using a 70 degrees  arthroscope and a femoral tunnel is
      made by use of an outside-in technique with remnant preservation. This technique
      allows for easy viewing of the posterior side of the ACL and enables performance
      of an anatomic ACL reconstruction. 

PMID- 24749042
TI  - Arthroscopy-assisted closed reduction and percutaneous nail fixation of unstable
      ankle fractures: description of a minimally invasive procedure.
AB  - When one is surgically managing an unstable ankle fracture, anatomic reduction of
      the syndesmosis is typically accomplished using an open surgical approach. We
      propose an arthroscopically assisted technique that restores normal anatomy while
      using a percutaneously placed intramedullary nail to fix the fibula. The patient
      is positioned supine, and the ankle is placed under traction by use of a tensor
      bandage. Standard anteromedial and anterolateral arthroscopy portals are used.
      The joint is examined for bony, ligamentous, and chondral injury. Lateral
      malleolus fracture reduction is accomplished with pointed reduction forceps to
      apply traction and rotation to the tip of the distal fibula fragment. A
      retrograde fibular intramedullary nail (Acumed, Hillsboro, OR) is inserted under
      fluoroscopic guidance. Arthroscopy is then used to guide the reduction of the
      fibula and rotation of the fibula with placement of the arthroscope in the
      lateral gutter. Syndesmosis screws are placed once the fracture and syndesmosis
      reductions are confirmed through both fluoroscopy and arthroscopy. 

PMID- 24749043
TI  - Endoscopic shelf acetabuloplasty combined with labral repair, cam
      osteochondroplasty, and capsular plication for treating developmental hip
      dysplasia.
AB  - In addition to the underlying shallow acetabular deformity, a patient with hip
      dysplasia has a greater risk of development of a labral tear, a cam lesion, and
      capsular laxity. This combination of abnormalities exacerbates joint instability,
      ultimately leading to osteoarthritis. Unsurprisingly, only repairing the
      acetabular labrum remains controversial, and the outcome is unpredictable. In
      this technical note, with video, we demonstrate an entirely endoscopic approach
      for simultaneously repairing the most common mechanical abnormalities found in
      moderate hip dysplasia: labral repair, cam osteochondroplasty, capsular
      plication, and shelf acetabuloplasty using an autologous iliac bone graft. 

PMID- 24749044
TI  - Arthroscopic double-row anterior stabilization and bankart repair for the "high
      risk" athlete.
AB  - In addition to operative intervention for the patient with recurrent shoulder
      instability, current literature suggests that younger athletic patients unwilling
      to modify their activities may benefit from an early surgical shoulder
      stabilization procedure. Although open shoulder stabilization clearly has a role
      to play in some cases, we believe that further optimization of arthroscopic
      fixation techniques may allow us to continue to refine the indications for open
      stabilization. In particular, when an arthroscopic approach is used for
      capsulolabral repair in relatively high-risk groups, it may be beneficial to use
      a double-row repair technique. We describe our technique for shoulder
      stabilization through double-row capsulolabral repair of a soft-tissue Bankart
      lesion in the high-risk patient with shoulder instability or the patient with a
      small osseous Bankart lesion. 

PMID- 24749045
TI  - Pectoralis major repair with cortical button technique.
AB  - Pectoralis major tendon ruptures can lead to significant functional deficits that
      affect high-level athletic and labor-intensive activities. In active populations
      operative repair of the ruptured pectoralis major tendon has shown significant
      advantages over nonoperative treatment. We describe a novel surgical technique
      for pectoralis major repair with tension button fixation. This study included 12
      recreational athletes and 2 professional athletes. The initial results were
      measured subjectively after a minimum of 6 months by the Single Assessment
      Numeric Evaluation score, the American Shoulder and Elbow Surgeons score, and the
      ability to return to the patient's sport at a preinjury level. Objectively,
      strength was measured with resisted horizontal adduction of the arm for both
      repaired and contralateral sides. Of the 12 recreational patients, 8 returned to
      their sport at preinjury levels, and the 2 professional athletes returned to
      their sport at full capacity in the National Football League. The mean Single
      Assessment Numeric Evaluation score was 87, and the mean American Shoulder and
      Elbow Surgeons scores were 99 for both the operative and contralateral sides.
      Isokinetic strength testing showed no significant differences between the
      operative and nonoperative sides. Patients with pectoralis major tendons repaired
      with the proposed tensioned cortical button technique had excellent results. This
      new technique provides a reliable method of repair in an efficient and safe
      manner. 

PMID- 24749046
TI  - The use of the 70 degrees  arthroscope for anatomic femoral and tibial tunnel
      placement and tunnel viewing in anterior cruciate ligament reconstruction.
AB  - The use of the 70 degrees  arthroscope in knee surgery is not a new concept, and
      it is frequently used in posterior cruciate ligament reconstruction. There are
      previous reports of its use in anterior cruciate ligament surgery, but it has not
      achieved routine use. With the move toward anatomic anterior cruciate ligament
      reconstruction, it is recognized that accurate tunnel placement is vital for a
      good clinical outcome. Visualization of the femoral and tibial footprints can be
      variable with the use of only an anterolateral viewing portal, and it may be
      necessary to create accessory anteromedial portals, which can cause problems with
      instrument crowding. Overall, the 70 degrees  arthroscope provides an excellent
      view of the femoral and tibial footprints and a view of the full length of the
      femoral and tibial tunnels through a single anterolateral viewing portal. 

PMID- 24749047
TI  - Closed intramedullary derotational osteotomy and hip arthroscopy for cam
      femoroacetabular impingement from femoral retroversion.
AB  - Femoral retroversion is an uncommon cause of cam femoroacetabular impingement
      that may require surgical treatment beyond arthroscopic or open femoroplasty. We
      present the case of a young adult with bilateral severe femoral retroversion in
      whom such treatment failed. We discuss the rationale, surgical technique, and
      outcome of this patient, who underwent bilateral closed intramedullary
      derotational proximal femoral osteotomies and interlocked nailing with adjunctive
      pre- and post-osteotomy hip arthroscopies. Clinical improvement with normal foot
      progression angles, radiographic union, and resolution of bilateral cam
      femoroacetabular impingement from femoral retroversion was achieved. This surgery
      permits rapid institution of weight-bearing ambulation and an early
      rehabilitative program. Femoral retroversion may be an underappreciated and
      insufficiently treated cause of cam femoroacetabular impingement that may be
      readily detected and successfully remedied with this less invasive procedure. 

PMID- 24749048
TI  - Arthroscopic repair of a posterior bony humeral avulsion of the glenohumeral
      ligament with associated teres minor avulsion.
AB  - Humeral avulsion of the inferior glenohumeral ligament (HAGL) has recently gained
      more recognition as a cause of shoulder instability. Posterior HAGL lesions,
      being much more infrequent than anterior disruptions, have only recently been
      documented as a notable cause of posterior instability. We detail the treatment
      of a previously unreported case of a posterior HAGL variant lesion consisting of
      a bony avulsion with involvement of the teres minor tendon. Arthroscopic fixation
      was facilitated by use of a "sheathless" arthroscopic approach with a 70 degrees 
      arthroscope and suture anchor. 

PMID- 24749049
TI  - Inventing new medicines: The FGF21 story.
AB  - Since the discovery of insulin in 1921, protein therapeutics have become vital
      tools in the treatment of diabetes mellitus. This heritage has been extended with
      the comparatively recent introduction of recombinant and re-engineered insulins,
      in addition to the advent of GLP1 agonists. FGF21 represents an example of a
      novel experimental protein therapy which is able to induce favorable metabolic
      effects in various species ranging from rodents to man. The aim of this review is
      to communicate the story of the FGF21 drug discovery path from identification in
      a functional in vitro screen, to the eventual evaluation of its utility in
      patients. Given that the development of FGF21 advanced hand-in-hand with rapidly
      evolving scientific research around this target, we have also attempted to
      describe our view of recent developments regarding the mechanistic understanding
      of FGF21 biology. 

PMID- 24749051
TI  - Relationship status update for PTP1B and LepR: It's complicated.

PMID- 24749050
TI  - Action and therapeutic potential of oxyntomodulin.
AB  - Oxyntomodulin (OXM) is a peptide hormone released from the gut in post-prandial
      state that activates both the glucagon-like peptide-1 receptor (GLP1R) and the
      glucagon receptor (GCGR) resulting in superior body weight lowering to selective
      GLP1R agonists. OXM reduces food intake and increases energy expenditure in
      humans. While activation of the GCGR increases glucose production posing a
      hyperglycemic risk, the simultaneous activation of the GLP1R counteracts this
      effect. Acute OXM infusion improves glucose tolerance in T2DM patients making
      dual agonists of the GCGR and GLP1R new promising treatments for diabetes and
      obesity with the potential for weight loss and glucose lowering superior to that
      of GLP1R agonists. 

PMID- 24749052
TI  - Linking maternal obesity to early insulin resistance.

PMID- 24749054
TI  - On ceramides, other sphingolipids and impaired glucose homeostasis.
AB  - In most people with type 2 diabetes, progression from obesity to diabetes is
      accompanied by elevated tissue exposures to a variety of lipids. Among these
      lipid species, ceramides and more complex sphingolipids have gained recent
      attention as being pathophysiologically relevant for the development of insulin
      resistance and impaired glycemic control. Upon excess intake of saturated fat,
      ceramides accumulate in insulin sensitive tissues either as a consequence of de
      novo synthesis or through mobilization from complex sphingolipids. Clinical
      studies have confirmed positive correlation between plasma and tissue levels of
      several ceramide species and insulin resistance. At the cellular level, it has
      been demonstrated that ceramides impair insulin signaling and intracellular
      handling of glucose and lipids with resulting deleterious effects on cellular
      metabolism. Hence, we are reviewing whether therapeutic interventions aiming at
      reducing tissue exposure to ceramides or other sphingolipids represent viable
      therapeutic approaches to improve glucose metabolism in people with diabetes. 

PMID- 24749053
TI  - Adipokines - removing road blocks to obesity and diabetes therapy.
AB  - Prevention of obesity and therapeutic weight loss interventions have provided
      only limited long term success. Therefore there is an urgent need to develop
      novel pharmacological treatment strategies, which target mechanisms underlying
      positive energy balance, excessive fat accumulation and adverse fat distribution.
      Adipokines may have potential for future pharmacological treatment strategies of
      obesity and metabolic diseases, because they are involved in the regulation of
      appetite and satiety, energy expenditure, endothelial function, blood pressure,
      insulin sensitivity, adipogenesis, fat distribution and insulin secretion and
      others. There are important road blocks on the way from an adipokine candidate to
      the clinical use a therapeutic compound. Such road blocks include an incomplete
      understanding of the mechanism of action, resistance to a specific adipokine,
      side effects of the adipokine and others. This review focuses on the potential of
      selected adipokines as therapeutic tools or targets and discusses important road
      blocks, which currently prevent their clinical use. 

PMID- 24749055
TI  - Untangling the interplay of genetic and metabolic influences on beta-cell
      function: Examples of potential therapeutic implications involving TCF7L2 and
      FFAR1.
AB  - Deteriorating beta-cell function is a common feature of type 2 diabetes. In this
      review, we briefly address the regulation of beta-cell function, and discuss some
      of the main determinants of beta-cell failure. We will focus on the role of
      interactions between the genetic background and metabolic environment (insulin
      resistance, fuel supply and flux as well as metabolic signaling). We present data
      on the function of the strongest common diabetes risk variant, the single
      nucleotide polymorphism (SNP) rs7903146 in TCF7L2. As also mirrored by its
      interaction with glycemia on insulin secretion, this SNP in large part confers
      resistance against the incretin effect. Genetic influence on insulin secretion
      also interacts with free fatty acids, as evidenced by data on rs1573611 in FFAR1.
      Several medications marketed by now or currently under development for diabetes
      treatment engage these pathways, and therapeutic implications from these findings
      are soon to be expected. 

PMID- 24749057
TI  - Metabolic syndrome - Removing roadblocks to therapy: Antigenic immunotherapies.
AB  - Up to 25 per cent of the world's adult population may have the metabolic
      syndrome, a condition closely associated with central obesity. The metabolic
      syndrome is a major risk factor for cardiovascular disease and type 2 diabetes
      and therefore represents an important worldwide health problem. In addition to
      metabolic abnormalities such as raised fasting plasma glucose, high cholesterol
      and high blood pressure, there is consensus that obese subjects develop a state
      of low-grade chronic immune activation. This sustained pro-inflammatory response
      in fat tissue is thought to worsen insulin resistance and dyslipidemia. Likewise,
      the immune system contributes to the detrimental cascade of events leading to
      plaque formation in atherosclerosis. It has long been assumed that the innate arm
      of the immune system was the only key player, but emerging evidence suggests that
      there is in fact a sizeable adaptive immune component to obesity and
      cardiovascular disease. From a therapeutic perspective, it could be envisioned
      that immune modulation drugs such as cytokine inhibitors, co-stimulation blockers
      or anti-T cell agents could offer benefit. It is questionable, however, whether
      chronic treatment with for instance biologicals will have a favorable
      risk/benefit profile in a silent condition such as the metabolic syndrome. An
      attractive alternative could be the development of antigen-specific T cell
      therapies, not unlike those currently in various phases of development for type 1
      diabetes. In this article, we will give an overview of antigen-specific treatment
      modalities in type 1 diabetes, followed by a review of the evidence for T cell
      involvement in obesity and atherosclerosis. 

PMID- 24749056
TI  - Islet cell plasticity and regeneration.
AB  - Insulin-dependent diabetes is a complex multifactorial disorder characterized by
      loss or dysfunction of beta-cells resulting in failure of metabolic control. Even
      though type 1 and 2 diabetes differ in their pathogenesis, restoring beta-cell
      function is the overarching goal for improved therapy of both diseases. This
      could be achieved either by cell-replacement therapy or by triggering intrinsic
      regenerative mechanisms of the pancreas. For type 1 diabetes, a combination of
      beta-cell replacement and immunosuppressive therapy could be a curative
      treatment, whereas for type 2 diabetes enhancing endogenous mechanisms of beta
      cell regeneration might optimize blood glucose control. This review will briefly
      summarize recent efforts to allow beta-cell regeneration where the most promising
      approaches are currently (1) increasing beta-cell self-replication or neogenesis
      from ductal progenitors and (2) conversion of alpha-cells into beta-cells. 

PMID- 24749058
TI  - Beneficial effects of breastfeeding in women with gestational diabetes mellitus.
AB  - Gestational diabetes mellitus (GDM) increases the future risk of developing type
      2 diabetes mellitus (T2DM). There is now a growing evidence that breastfeeding
      has short- and long-term health benefits for mothers with GDM. Mothers with GDM
      who breastfeed have improved lipid and glucose metabolic profiles for the first 3
      months after birth. However, women with GDM are less likely to breastfeed and, if
      they do, breastfeeding is usually continued for a shorter duration compared with
      women without GDM. One long-term prospective study followed women with GDM from
      delivery for up to 19 years postpartum, and found that breastfeeding for >=3
      months reduced the risk of T2DM and delayed the development of T2DM by a further
      10 years compared with breastfeeding for <3 months. However, the physiological
      mechanisms underlying the protective effects of breastfeeding are still unknown,
      even though it is important to gain a full understanding of the pathways involved
      in these effects. Therefore, the purpose of this review is to provide a
      comprehensive analysis of the recent developments in the field of GDM and
      breastfeeding. We reviewed data from animal experiments and human studies. We
      also provide insight into the molecular pathways and describe promising topics
      for future research. 

PMID- 24749059
TI  - A glucagon analog chemically stabilized for immediate treatment of life
      threatening hypoglycemia.
AB  - For more than half a century glucagon has been used as a critical care medicine
      in the treatment of life-threatening hypoglycemia. It is commercially supplied as
      a lyophilized powder intended to be solubilized in dilute aqueous hydrochloric
      acid immediately prior to administration. We have envisioned a "ready-to-use"
      glucagon as a drug of more immediate and likely use. Through a series of
      iterative changes in the native sequence we have identified glucagon analogs of
      appreciably enhanced aqueous solubility at physiological pH, and of chemical
      stability suitable for routine medicinal use. The superior biophysical properties
      were achieved in part through adjustment of the isoelectric point by use of a C
      terminal Asp-Glu dipeptide. The native glutamines at positions 3, 20 and 24 as
      well as the methionine at 27 were substituted with amino acids of enhanced
      chemical stability, as directed by a full alanine scan of the native hormone. Of
      utmost additional importance was the dramatically enhanced stability of the
      peptide when Ser16 was substituted with alpha,aminoisobutyric acid (Aib), a
      substitution that stabilizes peptide secondary structure. The collective set of
      changes yield glucagon analogs of comparable in vitro and in vivo biological
      character to native hormone but with biophysical properties much more suitable
      for clinical use. 

PMID- 24749060
TI  - Improved metabolic phenotype of hypothalamic PTP1B-deficiency is dependent upon
      the leptin receptor.
AB  - Protein tyrosine phosphatase 1B (PTP1B) is a known regulator of central metabolic
      signaling, and mice with whole brain-, leptin receptor (LepRb) expressing cell-,
      or proopiomelanocortin neuron-specific PTP1B-deficiency are lean, leptin
      hypersensitive, and display improved glucose homeostasis. However, whether the
      metabolic effects of central PTP1B-deficiency are due to action within the
      hypothalamus remains unclear. Moreover, whether or not these effects are
      exclusively due to enhanced leptin signaling is unknown. Here we report that mice
      with hypothalamic PTP1B-deficiency (Nkx2.1-PTP1B(-/-)) display decreased body
      weight and adiposity on high-fat diet with no associated improvements in glucose
      tolerance. Consistent with previous reports, we find that hypothalamic deletion
      of the LepRb in mice (Nkx2.1-LepRb(-/-)) results in extreme hyperphagia and
      obesity. Interestingly, deletion of hypothalamic PTP1B and LepRb (Nkx2.1-PTP1B(-/
      ):LepRb(-/-)) does not rescue the hyperphagia or obesity of Nkx2.1-LepRb(-/-)
      mice, suggesting that hypothalamic PTP1B contributes to the central control of
      energy balance through a leptin receptor-dependent pathway. 

PMID- 24749061
TI  - Control of obesity and glucose intolerance via building neural stem cells in the
      hypothalamus.
AB  - Neural stem cells (NSCs) were recently revealed to exist in the hypothalamus of
      adult mice. Here, following our observation showing that a partial loss of
      hypothalamic NSCs caused weight gain and glucose intolerance, we studied if NSCs
      based cell therapy could be developed to control these disorders. While
      hypothalamus-implanted NSCs failed to survive in mice with obesity, NF-kappaB
      inhibition induced survival and neurogenesis of these cells, leading to effects
      in counteracting obesity and glucose intolerance. To generate an alternative cell
      source, we revealed that iPS-derived NSCs were converted into htNSCs by
      neuropeptide treatment. Of note, obesity condition potentiated the transfer of
      carotid artery-injected NSCs into the hypothalamus. These iPS-derived cells when
      engineered with NF-kappaB inhibition were also effective in reducing obesity and
      glucose intolerance, and neurogenesis towards POMCergic and GABAergic lineages
      was accountable. In conclusion, building NSCs in the hypothalamus represents a
      strategy for controlling obesity and glucose disorders. 

PMID- 24749062
TI  - Downregulation of IRS-1 in adipose tissue of offspring of obese mice is
      programmed cell-autonomously through post-transcriptional mechanisms.
AB  - We determined the effects of maternal diet-induced obesity on offspring adipose
      tissue insulin signalling and miRNA expression in the aetiology of insulin
      resistance in later life. Although body composition and glucose tolerance of 8
      week-old male offspring of obese dams were not dysregulated, serum insulin was
      significantly (p<0.05) elevated. Key insulin signalling proteins in adipose
      tissue were down-regulated, including the insulin receptor, catalytic (p110beta)
      and regulatory (p85alpha) subunits of PI3K as well as AKT1 and 2 (all p<0.05).
      The largest reduction observed was in IRS-1 protein (p<0.001), which was
      regulated post-transcriptionally. Concurrently, miR-126, which targets IRS-1, was
      up-regulated (p<0.05). These two features were maintained in isolated primary pre
      adipocytes and differentiated adipocytes in-vitro. We have therefore established
      that maternal diet-induced obesity programs adipose tissue insulin resistance. We
      hypothesise that maintenance of the phenotype in-vitro strongly suggests that
      this mechanism is cell autonomous and may drive insulin resistance in later life.

PMID- 24749063
TI  - GABA level, gamma oscillation, and working memory performance in schizophrenia.
AB  - A relationship between working memory impairment, disordered neuronal
      oscillations, and abnormal prefrontal GABA function has been hypothesized in
      schizophrenia; however, in vivo GABA measurements and gamma band neural synchrony
      have not yet been compared in schizophrenia. This case-control pilot study (N =
      24) compared baseline and working memory task-induced neuronal oscillations
      acquired with high-density electroencephalograms (EEGs) to GABA levels measured
      in vivo with magnetic resonance spectroscopy. Working memory performance,
      baseline GABA level in the left dorsolateral prefrontal cortex (DLPFC), and
      measures of gamma oscillations from EEGs at baseline and during a working memory
      task were obtained. A major limitation of this study is a relatively small sample
      size for several analyses due to the integration of diverse methodologies and
      participant compliance. Working memory performance was significantly lower for
      patients than for controls. During the working memory task, patients (n = 7) had
      significantly lower amplitudes in gamma oscillations than controls (n = 9).
      However, both at rest and across working memory stages, there were significant
      correlations between gamma oscillation amplitude and left DLPFC GABA level. Peak
      gamma frequency during the encoding stage of the working memory task (n = 16)
      significantly correlated with GABA level and working memory performance. Despite
      gamma band amplitude deficits in patients across working memory stages, both
      baseline and working memory-induced gamma oscillations showed strong dependence
      on baseline GABA levels in patients and controls. These findings suggest a
      critical role for GABA function in gamma band oscillations, even under conditions
      of system and cognitive impairments as seen in schizophrenia. 

PMID- 24749064
TI  - Impact of glutamate levels on neuronal response and cognitive abilities in
      schizophrenia.
AB  - Schizophrenia is characterized by impaired cognitive functioning, and brain
      regions involved in cognitive control processes show marked glutamatergic
      abnormalities. However, it is presently unclear whether aberrant neuronal
      response is directly related to the observed deficits at the metabolite level in
      schizophrenia. Here, 17 medicated schizophrenia patients and 17 matched healthy
      participants underwent functional magnetic resonance imaging (fMRI) when
      performing an auditory cognitive control task, as well as proton magnetic
      resonance spectroscopy ((1)H-MRS) in order to assess resting-state glutamate in
      the anterior cingulate cortex. The combined fMRI-(1)H-MRS analysis revealed that
      glutamate differentially predicted cortical blood-oxygen level-dependent (BOLD)
      response in patients and controls. While we found a positive correlation between
      glutamate and BOLD response bilaterally in the inferior parietal lobes in the
      patients, the corresponding correlation was negative in the healthy control
      participants. Further, glutamate levels predicted task performance in patients,
      such that lower glutamate levels were related to impaired cognitive control
      functioning. This was not seen for the healthy controls. These findings suggest
      that schizophrenia patients have a glutamate-related dysregulation of the brain
      network supporting cognitive control functioning. This could be targeted in
      future research on glutamatergic treatment of cognitive symptoms in
      schizophrenia. 

PMID- 24749065
TI  - Mouse SCNT ESCs have lower somatic mutation load than syngeneic iPSCs.
AB  - Ectopic expression of reprogramming factors has been widely adopted to reprogram
      somatic nucleus into a pluripotent state (induced pluripotent stem cells
      [iPSCs]). However, genetic aberrations such as somatic gene mutation in the
      resulting iPSCs have raised concerns regarding their clinical utility. To test
      whether the increased somatic mutations are primarily the by-products of current
      reprogramming methods, we reprogrammed embryonic fibroblasts of inbred C57BL/6
      mice into either iPSCs (8 lines, 4 previously published) or embryonic stem cells
      (ESCs) with somatic cell nuclear transfer (SCNT ESCs; 11 lines). Exome sequencing
      of these lines indicates a significantly lower mutation load in SCNT ESCs than
      iPSCs of syngeneic background. In addition, one SCNT-ESC line has no detectable
      exome mutation, and two pairs of SCNT-ESC lines only have shared preexisting
      mutations. In contrast, every iPSC line carries unique mutations. Our study
      highlights the need for improving reprogramming methods in more physiologically
      relevant conditions. 

PMID- 24749066
TI  - Do neonatal mouse hearts regenerate following heart apex resection?
AB  - The mammalian heart has generally been considered nonregenerative, but recent
      progress suggests that neonatal mouse hearts have a genuine capacity to
      regenerate following apex resection (AR). However, in this study, we performed AR
      or sham surgery on 400 neonatal mice from inbred and outbred strains and found no
      evidence of complete regeneration. Ideally, new functional cardiomyocytes,
      endothelial cells, and vascular smooth muscle cells should be formed in the
      necrotic area of the damaged heart. Here, damaged hearts were 9.8% shorter and
      weighed 14% less than sham controls. In addition, the resection border contained
      a massive fibrotic scar mainly composed of nonmyocytes and collagen disposition.
      Furthermore, there was a substantial reduction in the number of proliferating
      cardiomyocytes in AR hearts. Our results thus question the usefulness of the AR
      model for identifying molecular mechanisms underlying regeneration of the adult
      heart after damage. 

PMID- 24749067
TI  - FOXO3 promotes quiescence in adult muscle stem cells during the process of self
      renewal.
AB  - Skeletal muscle stem cells, or "satellite cells" (SCs), are required for the
      regeneration of damaged muscle tissue. Although SCs self-renew during
      regeneration, the mechanisms that govern SC re-entry into quiescence remain
      elusive. We show that FOXO3, a member of the forkhead family of transcription
      factors, is expressed in quiescent SCs (QSCs). Conditional deletion of Foxo3 in
      QSCs impairs self-renewal and increases the propensity of SCs to adopt a
      differentiated fate. Transcriptional analysis of SCs lacking FOXO3 revealed a
      downregulation of Notch signaling, a key regulator of SC quiescence. Conversely,
      overexpression of Notch intracellular domain (NICD) rescued the self-renewal
      deficit of FOXO3-deficient SCs. We show that FOXO3 regulates NOTCH1 and NOTCH3
      receptor expression and that decreasing expression of NOTCH1 and NOTCH3 receptors
      phenocopies the effect of FOXO3 deficiency in SCs. We demonstrate that FOXO3,
      perhaps by activating Notch signaling, promotes the quiescent state during SC
      self-renewal in adult muscle regeneration. 

PMID- 24749068
TI  - CRIPTO/GRP78 signaling maintains fetal and adult mammary stem cells ex vivo.
AB  - Little is known about the extracellular signaling factors that govern mammary
      stem cell behavior. Here, we identify CRIPTO and its cell-surface receptor GRP78
      as regulators of stem cell behavior in isolated fetal and adult mammary
      epithelial cells. We develop a CRIPTO antagonist that promotes differentiation
      and reduces self-renewal of mammary stem cell-enriched populations cultured ex
      vivo. By contrast, CRIPTO treatment maintains the stem cell phenotype in these
      cultures and yields colonies with enhanced mammary gland reconstitution capacity.
      Surface expression of GRP78 marks CRIPTO-responsive, stem cell-enriched fetal and
      adult mammary epithelial cells, and deletion of GRP78 from adult mammary
      epithelial cells blocks their mammary gland reconstitution potential. Together,
      these findings identify the CRIPTO/GRP78 pathway as a developmentally conserved
      regulator of fetal and adult mammary stem cell behavior ex vivo, with
      implications for the stem-like cells found in many cancers. 

PMID- 24749069
TI  - Epidermal growth factor treatment of the adult brain subventricular zone leads to
      focal microglia/macrophage accumulation and angiogenesis.
AB  - One of the major components of the subventricular zone (SVZ) neurogenic niche is
      the specialized vasculature. The SVZ vasculature is thought to be important in
      regulating progenitor cell proliferation and migration. Epidermal growth factor
      (EGF) is a mitogen with a wide range of effects. When stem and progenitor cells
      in the rat SVZ are treated with EGF, using intracerebroventricular infusion,
      dysplastic polyps are formed. Upon extended infusion, blood vessels are recruited
      into the polyps. In the current study we demonstrate how polyps develop through
      distinct stages leading up to angiogenesis. As polyps progress,
      microglia/macrophages accumulate in the polyp core concurrent with increasing
      cell death. Both microglia/macrophage accumulation and cell death peak during
      angiogenesis and subsequently decline following polyp vascularization. This model
      of inducible angiogenesis in the SVZ neurogenic niche suggests involvement of
      microglia/macrophages in acquired angiogenesis and can be used in detail to study
      angiogenesis in the adult brain. 

PMID- 24749070
TI  - Identification of the niche and phenotype of the first human hematopoietic stem
      cells.
AB  - In various vertebrate species, the dorsal aorta (Ao) is the site of specification
      of adult hematopoietic stem cells (HSCs). It has been observed that the
      upregulation of essential hematopoietic transcription factors and the formation
      of specific intra-aortic hematopoietic cell clusters occur predominantly in the
      ventral domain of the Ao (AoV). In the mouse, the first HSCs emerge in the AoV.
      Here, we demonstrate that in the human embryo the first definitive HSCs also
      emerge asymmetrically and are localized to the AoV, which thus identifies a
      functional niche for developing human HSCs. Using magnetic cell separation and
      xenotransplantations, we show that the first human HSCs are CD34(+)VE
      cadherin(+)CD45(+)C-KIT(+)THY-1(+)Endoglin(+)RUNX1(+)CD38(-/lo)CD45RA(-). This
      population harbors practically all committed hematopoietic progenitors and is
      underrepresented in the dorsal domain of the Ao (AoD) and urogenital ridges
      (UGRs). The present study provides a foundation for analysis of molecular
      mechanisms underpinning embryonic specification of human HSCs. 

PMID- 24749071
TI  - Identification of multipotent progenitors that emerge prior to hematopoietic stem
      cells in embryonic development.
AB  - Hematopoiesis in the embryo proceeds in a series of waves, with primitive
      erythroid-biased waves succeeded by definitive waves, within which the properties
      of hematopoietic stem cells (multilineage potential, self-renewal, and
      engraftability) gradually arise. Whereas self-renewal and engraftability have
      previously been examined in the embryo, multipotency has not been thoroughly
      addressed, especially at the single-cell level or within well-defined
      populations. To identify when and where clonal multilineage potential arises
      during embryogenesis, we developed a single-cell multipotency assay. We find
      that, during the initiation of definitive hematopoiesis in the embryo, a defined
      population of multipotent, engraftable progenitors emerges that is much more
      abundant within the yolk sac (YS) than the aorta-gonad-mesonephros (AGM) or fetal
      liver. These experiments indicate that multipotent cells appear in concert within
      both the YS and AGM and strongly implicate YS-derived progenitors as contributors
      to definitive hematopoiesis. 

PMID- 24749072
TI  - Divisional history and hematopoietic stem cell function during homeostasis.
AB  - We investigated the homeostatic behavior of hematopoietic stem and progenitor
      cells (HSPCs) temporally defined according to their divisional histories using an
      HSPC-specific GFP label-retaining system. We show that homeostatic hematopoietic
      stem cells (HSCs) lose repopulating potential after limited cell divisions. Once
      HSCs exit dormancy and accrue divisions, they also progressively lose the ability
      to return to G0 and functional activities associated with quiescent HSCs. In
      addition, dormant HSPCs phenotypically defined as multipotent progenitor cells
      display robust stem cell activity upon transplantation, suggesting that temporal
      quiescence is a greater indicator of function than cell-surface phenotype. Our
      studies suggest that once homeostatic HSCs leave dormancy, they are slated for
      extinction. They self-renew phenotypically, but they lose self-renewal activity.
      As such, they question self-renewal as a characteristic of homeostatic,
      nonperturbed HSCs in contrast to self-renewal demonstrated under stress
      conditions. 

PMID- 24749073
TI  - Huntingtin regulates mammary stem cell division and differentiation.
AB  - Little is known about the mechanisms of mitotic spindle orientation during
      mammary gland morphogenesis. Here, we report the presence of huntingtin, the
      protein mutated in Huntington's disease, in mouse mammary basal and luminal cells
      throughout mammogenesis. Keratin 5-driven depletion of huntingtin results in a
      decreased pool and specification of basal and luminal progenitors, and altered
      mammary morphogenesis. Analysis of mitosis in huntingtin-depleted basal
      progenitors reveals mitotic spindle misorientation. In mammary cell culture,
      huntingtin regulates spindle orientation in a dynein-dependent manner. Huntingtin
      is targeted to spindle poles through its interaction with dynein and promotes the
      accumulation of NUMA and LGN. Huntingtin is also essential for the cortical
      localization of dynein, dynactin, NUMA, and LGN by regulating their kinesin 1
      dependent trafficking along astral microtubules. We thus suggest that huntingtin
      is a component of the pathway regulating the orientation of mammary stem cell
      division, with potential implications for their self-renewal and differentiation
      properties. 

PMID- 24749074
TI  - Progenitor cell dynamics in the Newt Telencephalon during homeostasis and
      neuronal regeneration.
AB  - The adult newt brain has a marked neurogenic potential and is highly
      regenerative. Ventricular, radial glia-like ependymoglia cells give rise to
      neurons both during normal homeostasis and after injury, but subpopulations among
      ependymoglia cells have not been defined. We show here that a substantial portion
      of GFAP(+) ependymoglia cells in the proliferative hot spots of the telencephalon
      has transit-amplifying characteristics. In contrast, proliferating ependymoglia
      cells, which are scattered along the ventricular wall, have stem cell features in
      terms of label retention and insensitivity to AraC treatment. Ablation of neurons
      remodels the proliferation dynamics and leads to de novo formation of regions
      displaying features of neurogenic niches, such as the appearance of cells with
      transit-amplifying features and proliferating neuroblasts. The results have
      implication both for our understanding of the evolutionary diversification of
      radial glia cells as well as the processes regulating neurogenesis and
      regeneration in the adult vertebrate brain. 

PMID- 24749075
TI  - Detailed analysis of the genetic and epigenetic signatures of iPSC-derived
      mesodiencephalic dopaminergic neurons.
AB  - Induced pluripotent stem cells (iPSCs) hold great promise for in vitro generation
      of disease-relevant cell types, such as mesodiencephalic dopaminergic (mdDA)
      neurons involved in Parkinson's disease. Although iPSC-derived midbrain DA
      neurons have been generated, detailed genetic and epigenetic characterizations of
      such neurons are lacking. The goal of this study was to examine the authenticity
      of iPSC-derived DA neurons obtained by established protocols. We FACS purified
      mdDA (Pitx3 (Gfp/+) ) neurons derived from mouse iPSCs and primary mdDA (Pitx3
      (Gfp/+) ) neurons to analyze and compare their genetic and epigenetic features.
      Although iPSC-derived DA neurons largely adopted characteristics of their in vivo
      counterparts, relevant deviations in global gene expression and DNA methylation
      were found. Hypermethylated genes, mainly involved in neurodevelopment and basic
      neuronal functions, consequently showed reduced expression levels. Such
      abnormalities should be addressed because they might affect unambiguous long-term
      functionality and hamper the potential of iPSC-derived DA neurons for in vitro
      disease modeling or cell-based therapy. 

PMID- 24749076
TI  - Telomerase protects werner syndrome lineage-specific stem cells from premature
      aging.
AB  - Werner syndrome (WS) patients exhibit premature aging predominantly in mesenchyme
      derived tissues, but not in neural lineages, a consequence of telomere
      dysfunction and accelerated senescence. The cause of this lineage-specific aging
      remains unknown. Here, we document that reprogramming of WS fibroblasts to
      pluripotency elongated telomere length and prevented telomere dysfunction. To
      obtain mechanistic insight into the origin of tissue-specific aging, we
      differentiated iPSCs to mesenchymal stem cells (MSCs) and neural stem/progenitor
      cells (NPCs). We observed recurrence of premature senescence associated with
      accelerated telomere attrition and defective synthesis of the lagging strand
      telomeres in MSCs, but not in NPCs. We postulate this "aging" discrepancy is
      regulated by telomerase. Expression of hTERT or p53 knockdown ameliorated the
      accelerated aging phenotypein MSC, whereas inhibition of telomerase sensitized
      NPCs to DNA damage. Our findings unveil a role for telomerase in the protection
      of accelerated aging in a specific lineage of stem cells. 

PMID- 24749079
TI  - Global survey of polymyxin use: A call for international guidelines.
AB  - Polymyxins (polymyxin B and colistin) are older bactericidal antibiotics that are
      increasingly used to treat infections caused by multidrug-resistant (MDR) Gram
      negative bacteria. However, dosing and clinical use of these drugs vary widely.
      This survey was undertaken to reveal how polymyxins are used worldwide. Data were
      collected through a structured online questionnaire consisting of 24 questions
      regarding colistin usage patterns and indications as well as colistin dosage for
      adult patients. The questionnaire was disseminated in 2011 to relevant experts
      worldwide and was completed by 284 respondents from 56 different countries.
      Respondents from 11/56 countries (20%) had no access to colistin; 58/284
      respondents (20.4%) reported that in 2010 they experienced that colistin was not
      available when needed. Formulations of polymyxins used were reported as:
      colistimethate sodium (48.6%); colistin sulfate (14.1%); both (1.4%); polymyxin B
      (1.4%); and unknown. Intravenous formulations were used by 84.2%, aerosolised or
      nebulised colistin by 44.4% and oral colistin for selective gut decontamination
      by 12.7%. Common indications for intravenous colistin were ventilator-associated
      pneumonia, sepsis and catheter-related infections with MDR Gram-negative
      bacteria. Only 21.2% of respondents used a colistin-loading dose, mainly in
      Europe and North America. This survey reveals that the majority of respondents
      use colistin and a few use polymyxin B. The survey results show that colistin is
      commonly underdosed. Clear guidance is needed on indications, dosing and
      antibiotic combinations to improve clinical outcomes and delay the emergence of
      resistance. Colistin should be considered a last-resort drug and its use should
      be controlled. International guidelines are urgently needed.

PMID- 24749077
TI  - LET-418/Mi2 and SPR-5/LSD1 cooperatively prevent somatic reprogramming of C.
      elegans germline stem cells.
AB  - Throughout their journey to forming new individuals, germline stem cells must
      remain totipotent, particularly by maintaining a specific chromatin structure.
      However, the place epigenetic factors occupy in this process remains elusive. So
      far, "sensitization" of chromatin by modulation of histone arrangement and/or
      content was believed to facilitate transcription-factor-induced germ cell
      reprogramming. Here, we demonstrate that the combined reduction of two epigenetic
      factors suffices to reprogram C. elegans germ cells. The histone H3K4 demethylase
      SPR-5/LSD1 and the chromatin remodeler LET-418/Mi2 function together in an early
      process to maintain germ cell status and act as a barrier to block precocious
      differentiation. This epigenetic barrier is capable of limiting COMPASS-mediated
      H3K4 methylation, because elevated H3K4me3 levels correlate with germ cell
      reprogramming in spr-5; let-418 mutants. Interestingly, germ cells deficient for
      spr-5 and let-418 mainly reprogram as neurons, suggesting that neuronal fate
      might be the first to be derepressed in early embryogenesis. 

PMID- 24749080
TI  - Two novel compound heterozygous mutations in OPA3 in two siblings with OPA3
      related 3-methylglutaconic aciduria.
AB  - OPA3-related 3-methylglutaconic aciduria, or Costeff Optic Atrophy syndrome, is a
      neuro-ophthalmologic syndrome of early-onset bilateral optic atrophy and later
      onset spasticity, and extrapyramidal dysfunction. Urinary excretion of 3
      methylglutaconic acid and of 3-methylglutaric acid is markedly increased. OPA3
      related 3-methylglutaconic aciduria is due to mutations in the OPA3 gene located
      at 19q13.2-13.3. Here we describe two siblings with novel compound heterozygous
      variants in OPA3: c.1A>G (p.1M>V) in the translation initiation codon in exon 1
      and a second variant, c.142+5G>C in intron 1. On cDNA sequencing the c.1A>G
      appeared homozygous, indicating that the allele without the c.1A>G variant is
      degraded. This is likely due to an intronic variant; possibly the IVS1+5 splice
      site variant. The older female sibling initially presented with motor
      developmental delay and vertical nystagmus during her first year of life and was
      diagnosed subsequently with optic atrophy. Her brother presented with mildly
      increased hip muscle tone followed by vertical nystagmus within the first 6
      months of life, and was found to have elevated urinary excretion of 3
      methylglutaconic acid and 3-methylglutaric acid, and optic atrophy by 1.5 years
      of age. Currently, ages 16 and 7, both children exhibit ataxic gaits and
      dysarthric speech. Immunofluorescence studies on patient's cells showed
      fragmented mitochondrial morphology. Thus, though the exact function of OPA3
      remains unknown, our experimental results and clinical summary provide evidence
      for the pathogenicity of the identified OPA3 variants and provide further
      evidence for a mitochondrial pathology in this disease.

PMID- 24749081
TI  - Treatment of Cow's Milk Protein Allergy.
AB  - The diagnosis and treatment of cow's milk protein allergy (CMPA) is still a
      challenge. A systematic literature search was performed using Embase, Medline,
      The Cochrane Database of Systematic Reviews and Cochrane Central Register of
      Controlled Clinical Trials for the diagnosis and treatment of cow's milk allergy
      (CMA). Since none of the symptoms of CMPA is specific and since there is no
      sensitive diagnostic test (except a challenge test), the diagnosis of CMPA
      remains difficult. A "symptom-based score" is useful in children with symptoms
      involving different organ systems. The recommended dietary treatment is an
      extensive cow milk based hydrolysate. Amino acid based formula is recommended in
      the most severe cases. However, soy infant formula and hydrolysates from other
      protein sources (rice) are gaining popularity, as they taste better and are
      cheaper than the extensive cow's milk based hydrolysates. Recent meta-analyses
      confirmed the safety of soy and estimate that not more than 10-15% of CMPA
      infants become allergic to soy. An accurate diagnosis of CMA is still difficult.
      The revival of soy and the development of rice hydrolysates challenge the
      extensive cow's milk based extensive hydrolysates as first option and amino acid
      formula. 

PMID- 24749082
TI  - Sedation for pediatric endoscopy.
AB  - It is more difficult to achieve cooperation when conducting endoscopy in
      pediatric patients than adults. As a result, the sedation for a comfortable
      procedure is more important in pediatric patients. The sedation, however, often
      involves risks and side effects, and their prediction and prevention should be
      sought in advance. Physicians should familiarize themselves to the relevant
      guidelines in order to make appropriate decisions and actions regarding the
      preparation of the sedation, patient monitoring during endoscopy, patient
      recovery, and hospital discharge. Furthermore, they have to understand the
      characteristics of the pediatric patients and different types of endoscopy. The
      purpose of this article is to discuss the details of sedation in pediatric
      endoscopy. 

PMID- 24749083
TI  - Esophageal pH and Combined Impedance-pH Monitoring in Children.
AB  - Esophageal pH monitoring is considered the gold standard for the diagnosis of
      gastroesophageal reflux disease because of the normal ranges across the pediatric
      age range. However, this method can only detect acid reflux. Multichannel
      intraluminal impedance-pH (MII-pH) monitoring has recently been used for the
      detection of bolus reflux in infants and children. This method allows for the
      detection of liquid, gas or mixed reflux in addition to acid, weakly acidic or
      weakly alkaline reflux. MII-pH monitoring can record the direction of flow and
      the height of reflux, which are useful parameters to identify an association
      between symptoms and reflux. However, the technique is limited by its high cost
      and the lack of normative data of MII-pH in the pediatric population. Despite
      certain limitations, MII-pH monitoring will become more common and gradually
      replace pH monitoring in the future, because pH monitoring is part of MII-pH. 

PMID- 24749084
TI  - Clinical applications of gastrointestinal manometry in children.
AB  - Manometry is a noninvasive diagnostic tool for identifying motility dysfunction
      of the gastrointestinal tract. Despite the great technical advances in monitoring
      motility, performance of the study in pediatric patients has several limitations
      that should be considered during the procedure and interpretation of the test
      results. This article reviews the clinical applications of conventional
      esophageal and anorectal manometries in children by describing a technique for
      performing the test. This review will develop the uniformity required for the
      methods of performance, the parameters for measurement, and interpretation of
      test results that could be applied in pediatric clinical practice. 

PMID- 24749085
TI  - Clinical course of infliximab treatment in korean pediatric ulcerative colitis
      patients: a single center experience.
AB  - PURPOSE: Infliximab (IFX) is considered safe and effective for the treatment of
      ulcerative colitis (UC) in both adults and children. The aim of this study was to
      evaluate the short- and long-term clinical course of IFX in Korean children with
      UC. METHODS: Pediatric patients with UC who had received IFX infusions between
      November 2007 and May 2013 at Samsung Medical Center were retrospectively
      investigated. The clinical efficacy of IFX treatment was evaluated at 8 weeks
      (short term) and 54 weeks (long term) after the initiation of IFX treatment using
      the Pediatric Ulcerative Colitis Activity Index (PUCAI). The degree of response
      to IFX treatment was defined as complete response (PUCAI score=0), partial
      response (decrement of PUCAI score>=20 points), and non-response (decrement of
      PUCAI score <20 points). Adverse events associated with IFX treatment were also
      investigated. RESULTS: Eleven pediatric patients with moderate to severe UC had
      received IFX. The remission rate after IFX treatment was 46% (5/11) and 82%
      (9/11) at 8 weeks and 54 weeks after IFX treatment, respectively. All patients
      who were steroid-dependent before treatment with IFX achieved remission at 54
      weeks and were able to stop treatment with corticosteroids, while all steroid
      refractory patients failed to achieve remission at 54 weeks after treatment with
      IFX. CONCLUSION: Response to IFX treatment after 8 weeks may predict a favorable
      long-term response to IFX treatment in Korean pediatric UC patients.

PMID- 24749086
TI  - Molecular Analysis of the UGT1A1 Gene in Korean Patients with Crigler-Najjar
      Syndrome Type II.
AB  - PURPOSE: Crigler-Najjar syndrome type II (CN-2) is characterized by moderate non
      hemolytic unconjugated hyperbilirubinemia as a result of severe deficiency of
      bilirubin uridine diphosphate-glucuronosyltransferase (UGT1A1). The study
      investigated the mutation spectrum of UGT1A1 gene in Korean children with CN-2.
      METHODS: Five Korean CN-2 patients from five unrelated families and 50 healthy
      controls were enrolled. All five exons and flanking introns of the UGT1A1 gene
      were amplified by polymerase chain reaction (PCR) and the PCR products were
      directly sequenced. RESULTS: All children initially presented with neonatal
      jaundice and had persistent indirect hyperbilirubinemia. Homozygous p.Y486D was
      identified in all five patients. Three patients had an associated homozygous
      p.G71R and two a heterozygous p.G71R. The allele frequency of p.Y486D and p.G71R
      in healthy controls was 0 and 0.16, respectively. No significant difference in
      mean serum bilirubin levels was found between homozygous carriers of p.G71R and
      heterozygous carriers. CONCLUSION: The combination of homozygous p.Y486D and
      homozygous or heterozygous p.G71R is identified. The p.Y486D and p.G71R can be
      screened for the mutation analysis of UGT1A1 in Korean CN-2 patients.

PMID- 24749087
TI  - The Rate of Conversion from Immune-tolerant Phase to Early Immune-clearance Phase
      in Children with Chronic Hepatitis B Virus Infection.
AB  - PURPOSE: The spontaneous seroconversion rate of hepatitis B e antigen (HBeAg)
      positive chronic hepatitis B (CHB) virus infection in children is lower than that
      in adults. However, few studies have investigated the rate of transition from the
      immune-tolerant to the early immune-clearance phase in children. METHODS: From
      February 2000 to August 2011, we enrolled 133 children aged <18 years who had
      visited the Department of Pediatrics, Kyungpook National University Hospital. All
      subjects were in the immune-tolerant phase of HBeAg-positive CHB virus infection.
      The estimated transition rate into the early immune-clearance phase was
      calculated using the Kaplan-Meier method. RESULTS: Among the 133 enrolled
      pediatric CHB virus infection patients in the HBeAg-positive immune-tolerant
      phase, only 21 children (15.8%) had converted to the early immune-clearance
      phase. The average age at entry into active hepatitis was 10.6+/-4.8 years. The
      incidence of transition from the immune-tolerant to the early immune-clearance
      phase in these children was 1.7 episodes/100 patient-years. When analyzed by age,
      the estimated transition rate was 4.6%, 7.1%, and 28.0% for patients aged <6, 6
      12, >12 years, respectively. CONCLUSION: In children with CHB virus infection,
      the estimated rate of entry into the early immune-clearance phase was 28.0% for
      patients aged 12-18 years, which was significantly higher than that observed for
      children aged <12 years (11.7%; p=0.001).

PMID- 24749088
TI  - Neonatal Late-onset Hypocalcemia: Is There Any Relationship with Maternal
      Hypovitaminosis D?
AB  - PURPOSE: Neonatal late-onset hypocalcemia is defined as hypocalcemia developed
      after postnatal 3 days and associated with hypoparathyroidism, high phosphate
      diets and vitamin D deficiency. We experienced the increment of neonatal late
      onset hypocalcemia over 1 year. We tried to evaluate the relationship between
      late onset hypocalcemia and maternal hypovitaminosis D. METHODS: The medical
      records in the neonates with late-onset hypocalcemia during January 2007 to July
      2008 were retrospectively reviewed. Among those patients, 17 paired sera of
      mothers and neonates had collected. The levels of 25-OH vitamin D (25OHD) and
      intact parathyroid hormone (iPTH) were measured and were compared with neonate
      and the mother. RESULTS: The mean gestational age was 38(+1) weeks, and the mean
      body weight was 2,980 g. The onset time of hypocalcemia was 5.9 days of age. Most
      of them (88.2%) were feeding with formula and no one was only breast milk
      feeding. Of the 17 patients, 13 were born in spring or in winter. The median
      levels of calcium, phosphorus, alkaline phosphatase, iPTH and 25OHD were 7.0
      mg/dL, 8.6 mg/dL, 191.0 U/L, 57.2 pg/mL and 24.0 ng/mL in neonates. The levels of
      25OHD of 6 neonates were <20 ng/mL. A total of 16 mothers were considered vitamin
      D-deficient (<20 ng/mL), and vitamin D insufficient (20<25OHD<30 ng/mL).
      CONCLUSION: Neonatal late-onset hypocalcemia in our study seems to be influenced
      by maternal vitamin D deficiency and insufficiency. Sun tanning and vitamin D
      supplements from winter to spring would be helpful to prevent maternal vitamin D
      deficiency, one of the causes of neonatal late-onset hypocalcemia.

PMID- 24749089
TI  - Gastrointestinal Tract Involvement of Gorham's Disease with Expression of D2-40
      in Duodenum.
AB  - We present a case of a 13-year-old boy with Gorham's disease involving the
      thoracic and lumbar spine, femur, and gastrointestinal (GI) tract, which was
      complicated by recurrent chylothorax and GI bleeding. The presenting symptoms
      were intermittent abdominal pain, back pain, and melena.
      Esophagogastroduodenoscopy and colonoscopy showed no abnormal lesions, but
      duodenal biopsy showed marked dilation of the lymphatics in the mucosa and
      submucosa, which revealed positive staining with a D2-40 immunohistochemical
      marker. In cases of GI bleeding with osteolysis, the expression of a D2-40 marker
      in the lymphatic endothelium of the GI tract may help to diagnose GI involvement
      in Gorham's disease. To the best of our knowledge, this is the first case report
      to pathologically demonstrate intestinal lymphatic malformation as a cause of GI
      bleeding in Gorham's disease. 

PMID- 24749090
TI  - Epstein-barr virus infection with acute acalculous cholecystitis.
AB  - Acute acalculous cholecystitis (AAC) is an inflammation of the gallbladder in the
      absence of demonstrated stones. AAC is frequently associated with severe systemic
      inflammation. However, the exact etiology and pathogenesis of AAC still remain
      unclear. Acute infection with Epstein Barr virus (EBV) in childhood is usually
      aymptomatic, whereas it often presents as typical infectious mononucleosis
      symptoms such as fever, cervical lymphadenopathy, and hepatosplenomegaly. AAC may
      occur during the course of acute EBV infection, which is rarely encountered in
      the pediatric population. AAC complicating the course of a primary EBV infection
      is usually associated with a favorable outcome. Most of the patients recover
      without any surgical treatment. Therefore, the detection of EBV in AAC would be
      important for prediction of better prognosis. We describe the case of a 10-year
      old child who presented with AAC during the course of primary EBV infection, the
      first in Korea, and review the relevant literature. 

PMID- 24749091
TI  - Out with the old; in with the new.

PMID- 24749092
TI  - Treatment of segmental loss of the tibia by tibialisation of the fibula: a review
      of the literature.
AB  - Segmental defects of the tibia are challenging therapeutic problems for both the
      physician and the patient. These defects may be caused by severe trauma,
      infection, tumors and congenital processes. Several different techniques have
      been described for treatment of these defects including the Papineau technique,
      allograft reconstruction, bone transport using the Ilizarov frame, free
      vascularized fibular graft, tibiofibular synostosis and medial transport of the
      fibula with Tuli's technique, use of the Ilizarov frame and Huntington's
      procedure. All of these techniques have their specific advantages as well as
      disadvantages. Some of these techniques are used rarely i.e. the Papineau
      technique. The procedure of choice for most large tibial defects is bone
      transport with Ilizarov's technique; but in some cases the tibial remnant is
      inadequate for lengthening and we must use alternative treatments. In the three
      aforementioned techniques, the fibula is transferred with peroneal and anterior
      tibial muscles on a pedicle of peroneal vessels. This transfer retains a
      biological component of vital bone that allows for a shorter time for
      consolidation, increased remodeling potential and resistance to infection. It
      also has better long-term mechanical properties. Hypertrophy of the centralized
      fibula is described as attaining twice its original diameter or twice the size of
      the contralateral tibia. Hypertrophy has been seen in nearly all cases of the
      fibular centralization. Maximum hypertrophy is seen in children and besides
      patient age, is related to bony union and weight bearing. The reported time for
      hypertrophy of fibula varies from one to four years. No significant change in the
      diameter of the fibula was observed after five years. Fracture of tibialized
      fibula was not reported in many studies of fibular centralization with different
      techniques. In the reviewed articles, there were no cases of valgus deformity of
      the ankle. Either the patients were satisfied with the final results despite
      appearance of the lower extremity and the presence of some angular deformities,
      although in most cases, the deformities were mild. In this review we conclude
      that tibialisation of the fibula in selected cases is a reasonable alternative
      for the treatment of massive tibial defects. 

PMID- 24749093
TI  - Arterial damage accompanying supracondylar fractures of the humerus.
AB  - BACKGROUND: Arterial damage is sometimes associated with supracondylar fractures
      of the humerus. Diagnosis and careful management of the fracture and arterial
      repair is crucial. OBJECTIVES: The aim of this study was to determine the
      prevalence and outcome of supracondylar fractures of the humerus with signs and
      symptoms of limb ischemia, before and after arterial decompression or arterial
      reconstruction. MATERIALS AND METHODS: From September 2004 to July 2010, 225
      consecutive patients with supracondylar fracture of the humerus were
      prospectively recruited. RESULTS: From among 75 cases with Gartland type III
      fractures, 22 were found to have vascular injury.. Of the 22 cases with vascular
      injury, 7 patients underwent arterial reconstruction. The other 15 received
      arterial decompression. All patients had a satisfactory outcome. CONCLUSIONS: A
      high level of suspicion and careful clinical evaluation leading to an early
      diagnosis and management of vascular injury accompanying supracondylar fracture
      is very important to prevent unnecessary sequelae ranging from limb claudication,
      and compartment syndrome to more severe complications like Volkmann's contracture
      and even limb loss.

PMID- 24749095
TI  - Addition of clonidine in caudal anesthesia in children increases duration of post
      operative analgesia.
AB  - BACKGROUND: Pain in infancy is a developmental process. Due to the underdeveloped
      pain pathways in the spinal cord, the threshold of stimulation and sensation of
      pain is low at birth and has potential impacts on increasing the central effects
      of pain. Primary trauma during infancy can cause long term changes in structure
      and function of pain pathways that continue until adulthood. Lack of pain
      management in children can result in morbidity and mortality. OBJECTIVES: In this
      study we examined the duration of post-operative analgesia in children when
      clonidine is added to bupivacaine in caudal anesthesia. MATERIALS AND METHODS: In
      this clinical trial, 40 children aged 1-8 years who were candidates for elective
      inguinal hernia repair were studied. Induction and maintenance of anesthesia were
      achieved using sodium thiopenthal, halothane and nitrous oxide. Children were
      randomly divided into 2 groups in a double-blind fashion, and were given caudal
      anesthesia with 0.125% bupivacaine (1ml/kg) alone or b bupivacaine plus 2 MUg/kg
      clonidine. Blood pressure and heart rate were recorded peri-operatively.
      Analgesia was evaluated using objective pain scale (OPS) and sedation was
      assessed using Ramsay sedation scale (RSS). Acetaminophen was administered
      rectally for cases with OPS score greater than five. RESULTS: Duration of
      analgesia was found to be significantly longer in the group given bupivacaine
      plus clonidine (mean 417.50 min vs. 162.00 min). Peri-operative hypotension or
      bradycardia, post-operative respiratory depression, nausea or vomiting were not
      recorded in any patient. CONCLUSIONS: We concluded that addition of clonidine to
      bupivacaine prolongs the duration of post-operative analgesia without any
      respiratory or hemodynamic side-effects.

PMID- 24749094
TI  - Combined rib-latissimus flap; the "picket fence" concept for reconstruction of
      upper tibia defects.
AB  - BACKGROUND: Upper tibia defects ,type3b Gustilo, due to huge size and volume are
      very difficult to reconstruct; usually several operations are needed for bone and
      soft tissue defects and the definite one stage reconstruction is yet to be found.
      OBJECTIVES: In this article we reintroduce the rib- latissimus flap as an
      acceptable method to reconstruct tibia defects in selected cases. MATERIALS AND
      METHODS: The latissimus muscle with one or two ribs revascualrized by reverse
      flow from perforators is harvested; the ribs are bisected after harvest yielding
      four to six struts of vascularized bone to fill the huge upper tibia defect.
      Internal fixation is very important and we favor LCP plates for long bone
      fixation and the rib struts are fixed in place by small titanium screws to
      maintain the "picket fence" design. The muscle is then wrapped around the ribs
      and the defect is completely reconstructed. RESULTS: During the past 9 years we
      have used the rib-latissimus dorsi (RLD) muscle flap, without serratus muscle, in
      7 patients with combined bone and soft tissue defects of the upper tibia. All the
      flaps healed without any major complications and only one stress fracture was
      seen and treated. The ribs healed and in a median of 14 months hypertrophied to
      the size of the upper tibia. Nonunion was not observed and patients with lower
      extremity defects were able to bear full weight within an average of seven
      months. CONCLUSIONS: The fractures of tibia type 3a and 3b Gustilo are
      devastating injuries requiring several operations. Several combinations of RLD
      Serratus have already been reported but a rib-LD muscle with "picket fence"
      design has not been reported .The RLD transfer with two ribs divided into four
      struts for bone coverage and muscle to cover all the upper tibia soft tissue
      defect can be a useful tool in the armamentarium of the surgeon treating combined
      defects in a single stage.

PMID- 24749096
TI  - Milligan-Morgan Hemorrhoidectomy vs Stapled Hemorrhoidopexy.
AB  - BACKGROUND: The stapled hemorrhoidopexy (SH) is a procedure for prolapse and
      hemorrhoids . At first SH seemed to be a good alternative for the Milligan Morgan
      (MM) hemorrhoidectomy and preliminary results in early 2000 confirmed it.
      However, further studies and evaluation of long-term results showed poorer
      outcomes. OBJECTIVES: This study aimed to evaluate and compare the results of
      these 2 surgical procedures in terms of recovery, improvement of symptoms and
      incidence of complications. MATERIALS AND METHODS: This study was conducted from
      April 2008 to August 2010. A total of 80 patients were divided into 2 groups of
      40 each. In the SH group, there were 24 males (60%) and 16 females (40%) with a
      mean age of 48 +/- 12.5 yrs. In the MM group, there were 30 males (75%) and 10
      females (25%) with a mean age of 50.6 +/- 17.3 yrs. Patients with grade 3 and 4
      prolapsed hemorrhoids were entered in the study. Data were entered using SPSS
      software and analyzed using t-test and Chi-square test. RESULTS: The two groups
      had no significant difference in terms of age or sex. Duration of surgery was 35
      +/- 7 minutes in the SH and 23.6 +/- 13.5 minutes in the MM group. This
      difference was statistically significant (P = 0.000). Post-operative pain and
      complete pain relief was slightly lower in the MM group (not significant).
      Hospital stay was significantly longer in the MM group (P = 0.003). Return to
      work was similar in both groups. Three patients in the SH group (7.5%) and 2 in
      the MM group (5%) had hemorrhoid recurrence. CONCLUSIONS: Both techniques are
      efficient treatment methods for grade III and IV hemorrhoids and are associated
      with greater than 95% recovery rate. Overall, outcomes are the same in both
      techniques. Lower postoperative pain was the only advantage of SH over MM
      technique.

PMID- 24749097
TI  - Experience with reverse sural flap to cover defects of the lower leg and foot.
AB  - BACKGROUND: Coverage of traumatic soft-tissue defects in the lower limb is a
      common procedure. OBJECTIVES: The purpose of this prospective case series study
      was explore the capacity of the perforator-based sural flap in reconstruction
      surgery of patients with high velocity gunshot wounds in the distal third of the
      leg and heel pad of the foot. PATIENTS AND METHODS: A prospective case series
      study was undertaken to assess the sural fasciocutaneous flap carried out in our
      hospital, from 2010 to 2011. This case series study comprised eight patients,
      seven men and one woman with an average age of 35 years (19-55) and with a mean
      follow-up duration of 13 months (6-24 months). All patients had a history of a
      gunshot wound in distal part of the leg and heel pad of the foot with large soft
      tissue defects; treatment was done using the reverse sural flap. RESULTS: We
      performed reverse sural flaps in eight gunshot patients, to cover the defects of
      the lower leg and foot. Surgical site infection observed in one patient (12.5%)
      was treated successfully with antibiotic therapy. The reverse sural flap provided
      a satisfactory coverage for gunshot defects in all the patients. CONCLUSIONS:
      Reverse sural flap is a useful and versatile reconstructive method in patients
      with gunshot wounds of the lower leg and foot.

PMID- 24749098
TI  - Assessment of impulse noise level and acoustic trauma in military personnel.
AB  - BACKGROUND: Military personnel are usually exposed to high levels of impulse
      noise (IN) which can lead to hearing loss. OBJECTIVES: The purpose of this study
      was to assess the effects of relatively low level exposure of impulse noise (IN)
      during shooting practice on hearing using pure tone audiometry (PTA) and
      transiently evoked otoacoustic emission (TEOAE) in military personnel. MATERIALS
      AND METHODS: Forty male soldiers (mean age 20.08 years) were recruited for the
      study. Prior to their first shooting practice, PTA and TEOAE were recorded. After
      15 minutes and one week post- practice PTA and TEOAE were compared. RESULTS:
      Immediately after shooting practice significant differences in PTA at 500, 1000,
      and 4000 Hz were observed for the right ear and no significant difference at any
      frequency for the left ear. There was a significant difference in the amplitude
      of TEOAE 15 minutes after shooting practice at 500, 1000, 2000, 3000, and 4000 Hz
      in the right ear, while for the left ear the difference was significant at 1000
      and 2000 Hz. One week after exposure a significant difference at 500 and 4000 Hz
      was found only in the right ear and a significant difference in the amplitude of
      TEOAE was observed at 500, 1000, 2000, 3000, and 4000 Hz. CONCLUSIONS: Even
      exposure lower than permissible levels may lead to acoustic trauma. TEOAE is more
      sensitive than PTA in detecting early hearing loss after military shooting
      exercises. Hearing protection equipment and appropriate surveillance programs are
      recommended.

PMID- 24749099
TI  - Comparison of the efficacy of two local haemostatic agents.
AB  - BACKGROUND: In modern life, the incidence of traumatic injuries increases daily.
      In accidents which lead to trauma, massive bleeding is the main cause of death.
      Nowadays, many different chemical and herbal agents are available for quick
      control of bleeding. OBJECTIVES: In this study, we compare the effectiveness of
      two different types of chemical agents for control of bleeding in an animal
      model. MATERIALS AND METHODS: This research was done comparing two
      hemostaticagents- "Chitohem" and "Quikclot". Ten healthy IR Iranian sheep were
      chosen and were blindly divided into two different groups. In each of the groups,
      one of the aforementioned agents was to be applied. First, four main limb
      arteries of the sheep were dissected linearly and after measuring the volume of
      bleeding in the first 60 seconds, the chemical agent was applied to the site of
      bleeding. After that, the duration of bleeding, the volume of bleeding and the
      secondary blood pressure were measured and compared. RESULTS: There were no
      significant differences between the primary features of the animals in two groups
      (Weight, Baseline Systolic Blood Pressure and Pre-treatment Blood loss). In
      dependent quantities such as the volume of bleeding after the usage of chemical
      agents, secondary systolic blood pressure, the results were in favor of "Quick
      Clot" (P < 0.001 for volume of bleeding, P = 0.008 for secondary blood pressures
      and P < 0.001 for the necessary time for the bleeding to stop). CONCLUSIONS: In
      this study, it seems that activity of "Quikclot" in cessation of bleeding of
      large arterial vessels was slightly better than "Chitohem". Due to limitations
      which we had in this study, further studies are necessary to show the actual
      differences between these agents and their side effects.

PMID- 24749100
TI  - Assigning residents of emergency medicine to screen patients before admission: a
      strategy to overcome overcrowding.
AB  - BACKGROUND: The overcrowded hospital is an unsafe one. Overcrowding the emergency
      department (ED) results in increased patient suffering, prolonged waiting time,
      deteriorating level of service, and on occasion, a worsened medical condition or
      even death. OBJECTIVES: This study proposes a strategy to overcome ED
      overcrowding. MATERIALS AND METHODS: The proportion of acute area admitted
      patients to screened patients (A/S), and the proportion of patients who were
      finally transferred to inpatient wards (W/A) to those admitted in ED acute area
      were investigated during 6 consecutive months. Emergency medicine residents were
      assigned to screen patients before ED admission and afterwards. RESULTS: The
      average A/S changed from 82.4% to 44.2% (P = 0.028), and the average W/A changed
      from 28.3% to 51.48% (P = 0.028) before and after screening patients
      respectively. The initiative resulted in 97 less patients in the acute area per
      day. CONCLUSIONS: Decreased number of acute area admitted patients, and increase
      W/A proportion showed that the initiative was successful in obviating ED
      overcrowding while provision of care to those most in need was not altered.

PMID- 24749101
TI  - Femoral pseudoaneurysms requiring surgical treatment.
AB  - BACKGROUND: Despite use of arterial closure devices (APCDs) and thrombin
      injection , surgery is needed at times to repair femoral pseudoaneurysms (FPA) in
      patients undergoing endovascular interventions. We analysed the indications and
      results of surgical repair in a tertiary referral center performing more than
      6.000 angiographies and/or interventions annually. OBJECTIVES: The aim of this
      retrospective observational study was to identify local and clinical factors
      related to the need of surgical repair. PATIENTS AND METHODS: In this
      retrospective study, 122 (0.06%) FPAs treated among 21060 patients over a period
      of five years were assessed. Patient characteristics and therapeutic procedures
      were analyzed through hospital records. RESULTS: There were 15.163 (72%) coronary
      and 5.897 (27%) peripheral interventions, respectively. In 89 (73%) patients, FPA
      was successfully treated by ultrasound guided compression (USGC) alone.Thirty
      three (28%) patients underwent open surgical repair. Indication for operative
      treatment was hemodynamic instability in 9 (7%) patients, rapidly expanding
      haematoma unsuitable for USGC or after unsuccessful USGC in 23 (19%). One (0.8%)
      patient had an arterio-venous fistula. Intraoperative findings suggest that
      atypical endovascular access (e.g. deep femoral artery, lateral or medial
      puncture) and multiple puncture sites and/or laceration of the vessel wall were
      related to the need for surgery in 22 (67%) cases. Most patients had active
      antithrombotic therapy. Gender or the nature of procedure (diagnostic vs.
      intervention) did not increase risk for open repair. One (0.8%) patient died. No
      amputations were performed. Mean hospital stay of patients undergoing open
      surgical repair was 11 (range 4-36) days. CONCLUSIONS: Technical puncture
      problems were identified in 2/3 of patients requiring open surgery.

PMID- 24749102
TI  - Intraosseous ganglion cyst of the lunate.
AB  - Intraosseous ganglia can affect the carpal bones of the hand and must be
      considered in the differential diagnosis of wrist pain. A 38-year-old female
      presented with a 14-month history of left wrist pain and a radiolucent cystic
      lesion was seen computed tomography (CT) scanning. Characteristic radiographic
      findings of a cyst in association with a fine sclerotic rim was apparent. We
      report an unusual presentation of a ganglion cyst in the lunate bone with
      excellent treatment outcome. 

PMID- 24749103
TI  - Improvements in the management of trauma patients with the introduction of a
      lower limb trauma coordinator.
AB  - Mortality and morbidity from trauma continues to be a serious, ubiquitous public
      health problem. Our short communication reports on the benefits of a dedicated
      lower limb trauma coordinator (LLTC) to the trauma service of a busy inner-London
      Plastics unit. This is based on a retrospective case-note based audit; performed
      19 months prior to the introduction of the LLTC and for 16 months after. After
      the introduction of a LLTC our statistical analysis demonstrated a significant
      improvement in trauma timings in terms of injury to referral time, time to first
      plastics operation and duration of inpatient stay. This suggests the use of a
      fully qualified nurse with an orthopaedic background as a coordinator may prove
      to be highly advantageous over a non-clinical administrator improving the overall
      journey of the lower limb trauma patient in the English National Health Service. 

PMID- 24749104
TI  - Avoiding traumatic injury to the tissues in the new millennium.

PMID- 24749105
TI  - Trauma to the Temporomandibular Joint Following Tooth Extraction via Dental
      Students.

PMID- 24749106
TI  - The discovery of PCSK9 inhibitors: A tale of creativity and multifaceted
      translational research.

PMID- 24749107
TI  - ENGAGE AF: Effective anticoagulation with factor Xa in next generation treatment
      of atrial fibrillation.

PMID- 24749108
TI  - TOPCAT misses its primary endpoint: Should spironolactone be abandoned in HFpEF?
AB  - Heart failure with preserved ejection fraction (HFpEF) continues to be a
      challenging form of heart failure - one in which no therapy has yet been proven
      to improve outcome. Aldosterone antagonists have previously been shown to improve
      survival in a wide spectrum of patients with heart failure with reduced ejection
      fraction (HFrEF), and more recently, small trials suggested that they might have
      role in HFpEF patients. The effect of spironolactone on clinical outcomes in
      HFpEF was tested in the TOPCAT study. 

PMID- 24749109
TI  - BLOCK-HF: CRT gains new ground.

PMID- 24749110
TI  - The role of Notch pathway in cardiovascular diseases.
AB  - The recent increase in human lifespan, coupled with unhealthy diets and
      lifestyles have led to an unprecedented increase in cardiovascular diseases. Even
      in the presence of a wide range of therapeutic options with variable efficacy,
      mortality due to heart failure is still high and there is a need to identify new
      therapeutic targets. Genetic and in vitro studies have implicated the Notch
      signalling in the development and maintenance of the cardiovascular system
      through a direct effect on biological functions of vascular cells (endothelial
      and vascular smooth muscle cells) and cardiomyocytes. Notch signalling is also
      involved in the modulation of inflammation, which plays a major role in causing
      and exacerbating cardiovascular diseases. The Notch pathway could represent a new
      therapeutic target for the treatment of cardiovascular diseases. 

PMID- 24749111
TI  - Exploring the biology of valvular heart disease: Time to move into the twenty
      first century.

PMID- 24749113
TI  - Ancient Alexandria and the dawn of medical science.

PMID- 24749112
TI  - Inclusion cylinder method for aortic valve replacement utilising the Ross
      operation in adults with predominant aortic stenosis - 99% freedom from re
      operation on the aortic valve at 15 years.
AB  - BACKGROUND: To report our experience with the Ross operation in patients with
      predominant aortic stenosis (AS) using an inclusion cylinder (IC) method.
      METHODS: Out of 324 adults undergoing a Ross operation, 204 patients of mean age
      of 41.3 years (limits 16-62) underwent this procedure for either AS or mixed AS
      and regurgitation (AS/AR) between October, 1992 and February, 2012, implanting
      the PA with an IC method. Clinical follow up and serial echo data for this group
      is 97% complete with late mortality follow up 99% complete. RESULTS: There has
      been zero (0%) early mortality, and late survival at 15 years is 98% (96%, 100%).
      Only one re-operation on the aortic valve for progressive aortic regurgitation
      (AR) has been required with freedom from re-operation on the aortic valve at 15
      years being 99% (96%, 100%). The freedom from all re-operations on the aortic and
      pulmonary valves at 15 years is 97% (94%, 100%). Echo analysis at the most recent
      study shows that 98% have nil, trivial or mild AR. Aortic root size has remained
      stable, shown by long-term (15 year) echo follow up. CONCLUSIONS: In an
      experience spanning 19 years, the Ross operation used for predominant AS using
      the IC method described, results in 99% freedom from re-operation on the aortic
      valve at 15 years, better than any other tissue or mechanical valve. For adults
      under 65 years without significant co-morbidities who present with predominant
      AS, the pulmonary autograft inserted with this technique gives excellent results.

PMID- 24749114
TI  - Cardiac amyloidosis and hypertrophic cardiomyopathy: A dangerous liaison.

PMID- 24749115
TI  - Lessons from patient-specific 3D models of the cardiac chambers after the Mustard
      operation.
AB  - The recent ability to create detailed 3D models of the atrial and ventricular
      chambers using CT, MRI and rapid prototyping offers unique opportunities to study
      the size and shape of the different cardiac chambers both before and following
      operation for complex cardiac anomalies. We here describe the techniques for
      creating detailed 3D models of the heart and demonstrate the utility of these
      techniques in a patient studied after the Mustard operation. This can give
      important insights into the changes in size and shape of the different chambers
      and the patterns of blood flow from the pulmonary and systemic veins to the
      'appropriate' ventricle. This information in turn could be extremely helpful in
      understanding and optimizing the overall hemodynamic function after the Mustard
      operation. 

PMID- 24749116
TI  - Hokusai-VTE: Edoxaban for the treatment of venous thromboembolism.
AB  - Venous thromboembolism is associated with a high morbidity and, if left
      untreated, may progress to fatal outcome. The standard treatment of venous
      thromboembolism consists of heparin followed by long-term treatment with a
      vitamin K antagonist. However, the use of vitamin K antagonist has several
      inherent problems and practical challenges. These challenges have prompted the
      search for new oral anticoagulant drugs including direct factor Xa inhibitors
      (e.g., rivaroxaban, apixaban and edoxaban) and thrombin inhibitors (e.g.,
      dabigatran). To date, results for dabigatran, rivaroxaban, apixaban, for the
      treatment of VTE have been published. Recently, results of the 4th new oral
      anticoagulant agent, edoxaban, have been published in the Hokusai-VTE study. This
      review discusses the Hokusai-VTE study with special emphasis on its salient
      features (compared to other new oral anticoagulant studies) in addition to an
      overview on some key lessons learnt. 

PMID- 24749117
TI  - Rectal ulcers and massive bleeding after hemorrhoidal band ligation while on
      aspirin.
AB  - Endoscopic hemorrhoidal band ligation is a well-established nonoperative method
      for treatment of bleeding internal hemorrhoids (grade 1 to 3). It is a safe and
      effective technique with a high success rate. Complications with this procedure
      are uncommon. Although rectal ulceration due to band ligation is a rare
      complication, it can cause life-threatening hemorrhage especially when patients
      are on medications which impair hemostasis like aspirin or non steroidal anti
      inflammatory drugs. We present 2 cases of massive lower gastro-intestinal
      bleeding in patients who had a band ligation procedure performed 2 wk prior to
      the presentation and were on aspirin at home. Both the patients were
      hemodynamically unstable requiring resuscitation. They required platelet and
      blood transfusions and were found to have rectal ulcers on colonoscopy done
      subsequently. The rectal ulcers corresponded to the site of band ligation. The
      use of aspirin by these patients would have caused defects in the hemostasis and
      may have predisposed them to massive bleeding in the presence of rectal ulcers
      occurring after the band ligation procedure. Managing aspirin before and after
      the ligation may be difficult especially since adequate guidelines are
      unavailable. Stopping aspirin in all the cases might not be safe and the decision
      should be individualized. 

PMID- 24749118
TI  - Left ventricular pseudoaneurysm: A case report and review of the literature.
AB  - Left ventricular (LV) pseudoaneurysm is a rare complication that is reported in
      less than 0.1% of all patients with myocardial infarction. It is the result of
      cardiac rupture contained by the pericardium and is characterized by the absence
      of myocardial tissue in its wall unlike true aneurysm which involves full
      thickness of the cardiac wall. The clinical presentation of these patients is
      nonspecific, making the diagnosis challenging. Transthoracic echocardiogram and
      cardiac magnetic resonance imaging are the noninvasive modalities whereas
      coronary arteriography and left ventriculography are invasive modalities used for
      the diagnosis. As this condition is lethal, prompt diagnosis and timely
      management is vital. 

PMID- 24749119
TI  - Varicocele repair in severe oligozoospermia: A case report of post-operative
      azoospermia.
AB  - Varicocele has been implicated as a cause in 35%-50% of patients with primary
      infertility and up to 81% of men with secondary infertility. Although a large
      number of reports have shown improvement in the semen parameters after correction
      of varicocele, other studies have suggested no benefit. We report the first case
      of azoospermia after surgery in a young infertile male patient with left-sided
      varicocele and severe oligozoospermia undergoing laparoscopic varicocelectomy. A
      pregnancy was only achieved with assisted reproductive technology because semen
      cryopreservation was performed before surgery. In the light of the above, the
      deterioration of sperm count after varicocele repair in patients with severe
      oligozoospermia could be due to irreversible impairment of spermatogenesis of
      such patients, together with the possible temporary damage of the surgical
      repair. This possible complication could therefore turn the severe
      oligozoospermia into an indication to perform cryopreservation before surgery, on
      both clinical and medico-legal grounds. Further research is needed before drawing
      definitive conclusions regarding the management of varicocele-related severe
      oligozoospermia. 

PMID- 24749120
TI  - Transcatheter aortic valve implantation in a 54-year-old patient with aggressive
      HIV.
AB  - We report a case of a 54-year-old patient who was denied surgical replacement for
      severe aortic stenosis because of complicated acquired immunodeficiency syndrome
      and who successfully underwent transcatheter aortic valve implantation at our
      institution. 

PMID- 24749121
TI  - Elective thoracotomy for pedicle screw removal to prevent severe aortic bleeding.
AB  - We present a case of a 33-year-old female who sustained multiple injuries of her
      spine, including spinous process fractures of C5 to C7 and a lamina fracture of
      C6 and C7. Her thoracic spine showed transverse process fractures of T4 to T10, a
      compression fracture and lamina fracture of T3, spinous process and transverse
      process fractures of T4 and T5, a rotation injury of T6, as well as a compression
      fracture of L1. Thirteen months after posterior thoracic spinal instrumentation,
      a pedicle screw was suspected to be in contact with the aorta, which was proved
      by computed tomography angiograms. Consequently, implant removal was planned with
      direct exposure of the aorta in order to allow for immediate repair if needed. So
      far, studies that compare different techniques to remove pedicle screws that are
      suspected to penetrate the aorta are missing. However, different techniques have
      been described in case reports, mainly minimally invasive endovascular techniques
      vs open techniques such as thoracotomy. 

PMID- 24749122
TI  - Osteoid osteoma of the elbow mimicking hemophilic arthropathy.
AB  - A case of osteoid osteoma of the elbow in a patient with hemophilia A is
      described. This male patient presented with chronic and nocturnal pain of the
      left elbow which was alleviated with acetaminophen. Besides pain, he also
      complained of stiffness. Before these complaints, he had recurrent bleedings in
      the elbow because of hemophilia. A delayed diagnosis of osteoid osteoma in the
      proximal part of the left ulna was established by a bone scan and a multislice
      spiral computed tomography (CT) scan. The lesion was surgically removed under CT
      guidance. The histopathological analyses did not show specific features of
      osteoid osteoma. Two months after the operation, the complaints decreased and the
      range of motion of the left elbow improved. A diagnosis of osteoid osteoma of the
      elbow should be considered in young adult patients with persistent elbow pain and
      histological confirmation is not always necessary. 

PMID- 24749123
TI  - Spontaneous rupture of the renal pelvis presenting as an urinoma in locally
      advanced rectal cancer.
AB  - A 29-year-old gentleman underwent a transverse colostomy for intestinal
      obstruction caused by advanced rectal carcinoma. On the 5(th) postoperative day,
      the patient developed a painful swelling on the right side of the abdomen. The
      contrast enhanced computed tomography of the abdomen revealed a right sided
      hydronephrosis, a large rent in the renal pelvis, and a large retroperitoneal
      fluid collection on the right side. Percutaneous nephrostomy and pigtail catheter
      drainage of the urinoma led to resolution of abdominal swelling. Development of a
      urinoma as a consequence of rectal carcinoma is highly unusual. Prompt imaging
      for confirmation of diagnosis, decompression of the renal pelvicalyceal system,
      and drainage of the urinoma limits morbidity. 

PMID- 24749124
TI  - Rare case of an abdominal mass: Reactive nodular fibrous pseudotumor of the
      stomach encroaching on multiple abdominal organs.
AB  - Reactive nodular fibrous pseudotumor (RNFP), which presents abdominal clinical
      manifestations and malignant radiographic results, usually requires radical
      resection as the treatment. However, RNFP has been recently described as an
      extremely rare benign post-inflammatory lesion of a reactive nature, which
      typically arises from the sub-serosal layer of the digestive tract or within the
      surrounding mesentery in association with local injury or inflammation. In
      addition, a postoperative diagnosis is necessary to differentiate it from the
      other reactive processes of the abdomen. Furthermore, RNFP shows a good prognosis
      without signs of recurrence or metastasis. A 16-year-old girl presented with a 3
      mo history of epigastric discomfort, and auxiliary examinations suggested a
      malignant tumor originating from the stomach; postoperative pathology confirmed
      RNFP, and after a 2-year follow-up period, the patient did not display any signs
      of recurrence. This case highlights the importance of preoperative pathology for
      surgeons who may encounter similar cases. 

PMID- 24749125
TI  - Investigation of Targetin, a Microtubule Binding Agent which Regresses the Growth
      of Pediatric High and Low Grade Gliomas.
AB  - BACKGROUND: Pediatric gliomas, the most common solid childhood neoplasm, manifest
      unique molecular signatures that distinguish them from adult gliomas.
      Unfortunately, most studies have focused on adult gliomas and extrapolate the
      findings to treat pediatric gliomas. In this study, we assessed the efficacy of
      Targetin, a folate conjugated analogue of Noscapine, on the treatment of
      pediatric low and high grade gliomas. METHOD: An assortment of standard cancer
      assays were used with different drug doses and experimental durations. RESULTS:
      We found that pediatric glioma cells are more susceptible to lower doses of
      Targetin than parental Noscapine. Targetin functions by disrupting the
      microtubule network, and can likewise perturb DNA synthesis, delay the cellular
      transition within the S and G2M cell cycle phases, diminish anchorage independent
      growth and the migratory/invasiveness of pediatric glioma cells. Moreover,
      Targetin impairs the expression of several regulators of cancer progression
      belonging to prominent signalling pathways in pediatric gliomas; including
      Platelet Derived Growth Factor alpha and some members of the Mitogen Activated
      Protein Kinase cascade. CONCLUSION: Targetin has an excellent anti-neoplastic
      profile and functions to modulate the expression of several genes belonging to
      key cancer progression pathways in pediatric gliomas. Collectively, findings from
      this study highlight the usefulness of Targetin for the treatment of pediatric
      high and low grade gliomas.

PMID- 24749126
TI  - In-Vitro and Ex-Vivo Investigations of the Microtubule Binding Drug Targetin on
      Angiogenesis.
AB  - BACKGROUND: Intervention aimed at disrupting or inhibiting newly formed vascular
      network is highly desired to attenuate the progression of angiogenesis-dependent
      diseases. In cancer, this is tightly associated with the generation of VEGF by
      hypoxia inducible factor-1alpha following its activation by hypoxia. In light of
      the multiple cellular roles played by microtubules and their involvement in the
      processing of the hypoxia inducible factor-1alpha transcript, modulation of
      microtubule dynamics is emerging as a logical approach to suppress tumor reliance
      on angiogenesis. Targetin is a novel noscapinoid that interferes with microtubule
      dynamicity and inhibits the growth of cell lines from many types of cancers.
      METHODS AND RESULTS: Utilizing in-vitro and ex-vivo angiogenic models, we
      discovered the vascular disrupting and anti-angiogenic properties of Targetin.
      Targetin disrupted pre-assembled capillary-like networks of human endothelial
      cells by severing cell-cell junctions, inhibiting endothelial cell proliferation
      and metabolic activity in the presence and absence of vascular endothelial growth
      factor (VEGF) and basic fibroblast growth factor (bFGF). Furthermore, we show
      that Targetin significantly inhibits the formation of neovasculature network
      sprouting from rat aortic explants stimulated with proangiogenic stimuli, namely
      VEGF or bFGF. CONCLUSION: We conclude that Targetin is a potential clinically
      promising anti-angiogenic agent for the treatment of many diseases including
      cancers.

PMID- 24749127
TI  - Utility of Transthoracic Echocardiography and Carotid Doppler Ultrasound in
      Differential Diagnosis and Management of Ischemic Stroke in a Developing Country.
AB  - OBJECTIVE: We sought to describe findings, diagnostic yield, cost effectiveness
      of transthoracic echocardiography (TEE) and Carotid doppler ultrasound (CDU) in
      ischemic stroke. METHODS: Cross sectional study at Mulago hospital, Uganda.
      Institutional ethical approval, patient consent was obtained. Patients eighteen
      years and above with ischemic stroke confirmed by brain computerized tomography
      (CT) scan and met inclusion criteria were selected. TTE and CDU were done as part
      of comprehensive assessment for stroke risk factors. Data was analyzed using SPSS
      14. Univariate analysis was done for social-demographics, abnormalities on
      cardiac imaging and diagnostic yield using TOAST criteria. Bivariate analysis for
      association between stroke risk factors, cardio-embolic stroke and other ischemic
      subtypes (diagnosed using clinical and CT scan features). Statistical
      significance was set at P<0.05. RESULTS: Of 139 screened patients with suspected
      stroke, 127 underwent brain CT scan as 12 died before CT. Eighty five were
      confirmed stroke by CT scan with 66 (77.6%) ischemic stroke, mean age 62 years
      (SD+16.6), 53% were male. Out of 66, 62 (93.9%) underwent both TTE and CDU.
      Although only 7 (11.3%) reported history of heart disease, 43 (69.3%) had
      abnormal findings on TTE with left atrial enlargement commonest in 21 (48.8%).
      Thirty eight (61.3%) had abnormal finding on CDU with atherosclerosis commonest
      in 28 (45.2%). Using clinical and CT scan features, atherosclerotic stroke was
      the commonest subtype in 29 (46.8%) then cardio-embolic 18 (27.3%). Only 6 (9.7%)
      patients had abnormal findings on TTE suggesting possible cardio-embolism by
      TOAST criteria. None had stenosis >50% on CDU. Multiple valvular lesions P<0.001,
      severe valvular lesions P=0.001 were associated with cardio-embolic stroke.
      CONCLUSIONS: Majority of ischemic stroke patients without previous history of
      heart disease had abnormal findings on TTE and CDU. Diagnostic yield for cardio
      embolic stroke by TOAST criteria was very low given the high cost involved for a
      developing country.

PMID- 24749128
TI  - Study of the correlationship link between microRNAs and nasopharyngeal carcinoma.
AB  - Nasopharyngeal carcinoma (NPC) is a polygenic disease related to a variety of
      factors. With the development of the microRNAs (miRNAs) technique, researchers
      found a close link between miRNAs and NPC. Differentially expressed miRNAs exist
      in NPC and normal nasopharyngeal tissues; radiotherapy and chemotherapy also
      affect the expression of miRNAs in NPC tissues. Further studies showed that
      dysregulation and ectopic expression of miRNAs were involved in the occurrence
      and development of NPC by affecting the expression of oncogenes or tumor
      suppressor genes, or acting on relevant signal transduction pathways. It is of
      great significance to investigate the miRNAs related to the occurrence and
      development of NPC for the prevention and treatment of NPC.

PMID- 24749129
TI  - Specific anti-gastric cancer effects of a recombinant plasmid expressing
      nonstructural protein 1 of parvovirus H1.
AB  - OBJECTIVE: To investigate the responsiveness of gastric tumor cells to the
      nonstructural protein (NS)1 of parvovirus H1, which has a preferential lytic
      growth cycle in cancer cells. METHODS: This study was carried out in Shanghai
      Institute of Digestive Disease, Renji Hospital, Shanghai, China from 2009 to
      2012. An NS1-expressing plasmid was introduced into gastric cell lines or nude
      mice bearing tumor grafts. Expression was monitored by tracking fluorescence tag
      and specific transcription. Tumor growth suppression was measured, and cell cycle
      dyshomeostasis was verified by flow cytometry. Cell cycle regulators' level was
      measured on both the transcription and protein level. RESULTS: Gastric cancer
      cells were efficiently suppressed in vitro, or in the xenograft mice model. The
      NS1 dependent tumor suppression was specific since plasmid-driven NS1 expression
      in some normal tissues, in particular, the lungs was not accompanied by adverse
      side effects. The NS1 expression was found to stall gastric cancer cells in the
      G0/G1 stage with accumulation of cycle regulator p21. CONCLUSION: The NS1
      expression can suppress gastric cancer cell growth both in vitro and in xenograft
      model, probably through induction of the cell cycle regulator p21. These results
      support further development of the parvoviral NS1 protein as an anti-cancer
      effector.

PMID- 24749130
TI  - Immature reticulocyte fraction is an early predictor of bone marrow recovery post
      chemotherapy in patients with acute leukemia.
AB  - OBJECTIVE: To establish the benefits of immature reticulocyte fraction (IRF)
      measurement using an automated hematology cells analyzer over absolute neutrophil
      count (ANC) in predicting bone marrow recovery post induction chemotherapy.
      METHODS: A prospective observational study was carried out in the Departments of
      Pathology, Medicine, and Pediatrics, Universiti Kebangsaan Malaysia, Medical
      Center (UKMMC), Kuala Lumpur, Malaysia during a period of 19 months from April
      2009 to December 2010 to assess the bone marrow recovery in patients with acute
      leukemia. A total of 22 patients in remission induction phases were enrolled in
      this study. The blood specimens were collected from day zero after chemotherapy,
      and every 3 days until patients recovered hematologically. All blood samples were
      measured for ANC and IRF using an automated hematology analyzer (Beckman-Coulter
      LH750). RESULTS: The percentage of patients showing IRF recovery earlier than ANC
      recovery was 63.6% (14 out of 22 patients). There was a significant difference in
      the mean number of days for IRF recovery as compared with ANC recovery (14.05 and
      17.18 days), p=0.005. CONCLUSION: This study proved that IRF was more useful in
      predicting bone marrow recovery in a patient with acute leukemia post induction
      chemotherapy compared with ANC. The IRF is not affected by infection, is easily
      measured, and inexpensive; thus, it is a reliable parameter to evaluate bone
      marrow reconstitution.

PMID- 24749131
TI  - Immune responses against Mycobacterium tuberculosis-specific proteins PE35 and
      CFP10 in mice immunized with recombinant Mycobacterium vaccae.
AB  - OBJECTIVE: To clone and express Mycobacterium tuberculosis (M. tuberculosis)
      proteins PE35 and culture filtrate protein (CFP)10 in Mycobacterium vaccae (M.
      vaccae), and subsequently, evaluate the humoral and cellular immunity responses
      against these recombinant constructs in mice. METHODS: The DNA of PE35 and CFP 10
      genes were cloned into the shuttle plasmid pDE22, and the recombinant plasmids
      were electroporated into M. vaccae. The recombinant constructs were then tested
      for expression of PE35 and CFP10 by Western immunoblotting using rabbit anti
      sera. Furthermore, splenocytes and sera from groups of 5 mice immunized with
      recombinant M. vaccae (rVaccae) were tested for cellular and humoral responses in
      proliferation, and antibody assays. Experiments were carried out in the
      laboratory of the Faculty of Medicine, Kuwait University, Safat, Kuwait between
      2009 and 2011. RESULTS: The results of Western immunoblot suggested the
      expression of only PE35. However, splenocyte assays showed positive proliferation
      in response to peptide pools, and 4 and 5 of the 6 overlapping synthetic peptides
      covering the sequence of PE35 and CFP10. In addition, positive antibody
      reactivity was detected with PE35 peptide pool and a single peptide, namely, P2.
      CONCLUSION: The expression of PE35 and CFP10 proteins in rVaccae constructs led
      to the induction of cellular immune responses to multiple epitopes.

PMID- 24749132
TI  - Seroprevalence, transmission, and associated factors of specific antibodies
      against cytomegalovirus among pregnant women and their infants in a regional
      study.
AB  - OBJECTIVE: To assess specific anti-cytomegalovirus (CMV) antibodies, clinical
      status, and demographic data in pregnant women and their infants in northeast
      Iran. METHODS: This cross-sectional study was conducted on 225 systematic
      randomly selected-pregnant women and their newborns attending public hospitals in
      Mashhad, Iran between December 2007 and January 2008. Two specialists performed
      clinical assessment and obtained the demographic data. The sera from mothers and
      the umbilical cord of infants were then collected at the time of delivery and
      anti-CMV antibodies, IgG, and IgM, were measured. RESULTS: Although, all mothers
      and their neonates were positive for anti-CMV IgG (100%), only 6 were positive
      for anti-CMV specific IgM (2.6%), and their infants were negative. However, in
      one infant the clinical features of CMV infection were observed by radiological
      evaluation (CT scan) (0.4%). There was no correlation between anti-CMV IgG in
      neonates and number of parity, history of abortion, mothers' and neonates' blood
      groups, gestational age, and economical status. However, the concentration of
      anti-CMV IgG in neonates with normal delivery was significantly lower than with
      cesarean delivery (p=0.03), and in girls compared with boys (p=0.04). CONCLUSION:
      Anti-CMV IgG transmission to neonates is associated with gender and type of
      delivery. Despite anti-CMV IgM showing active CMV infection in mothers, virus
      transmission to the fetus might not occur.

PMID- 24749133
TI  - Assessment of trace elements in sera of patients undergoing renal dialysis.
AB  - OBJECTIVE: To assess the serum levels of copper, zinc, iron, and lead in patients
      on maintenance dialysis. METHODS: This cross-sectional study performed at King
      Khalid University Hospital, Riyadh, Saudi Arabia between September 2011 and
      October 2012 included 42 patients with end stage renal disease on hemodialysis
      (HD), 18 patients on peritoneal dialysis (PD), and 18 normal controls. Serum
      copper, zinc, and lead levels were determined by atomic absorption
      spectrophotometry, and serum iron was determined by spectrophotometric
      determination. RESULTS: The median serum copper level in HD patients (20.5
      nmol/L; 95% confidence interval [CI]: 17.52-22.39; interquartile range [IQR]:
      16.40-24.20) was higher (p=0.001) than the controls (14.30 nmol/L; 95% CI: 9.72
      16.91; IQR: 9.70-17), and the PD patients (15.60 nmol/L; 95% CI: 14.17-16.66;
      IQR: 14.10-16.70). Although no different from PD patients' serum levels of zinc
      in HD patients (9.50 nmol/L; 95% CI: 7.83-12.09; IQR: 7.00-14.40) were lower than
      controls (13.20 nmol/L; 95% CI: 10.65-15.22; IQR: 10.58-15.35; p=0.03).
      Copper/zinc ratio in HD patients was 2.4, 2.5 in PD patients, and 0.88 in
      controls. The serum iron levels in HD patients (10 mmol/L; 95% CI: 8.03-11.96;
      IQR: 7-14.50; p=0.003), and PD patients (10 mmol/L; 95% CI 6.56-14.43; IQR 5.50
      15; p=0.03) were lower than controls. Serum lead levels in PD patients (0.11
      umol/L; 95% CI: 0.02-0.14; IQR: 0.02-0.14) were lower than HD patients (0.18
      umol/; 95% CI: 0.15-0.21; IQR: 0.13-0.25; p=0.005), and controls (0.15 umol/L;
      95% CI: 0.07-0.24; IQR: 0.06-0.25; p=0.04). CONCLUSION: Alterations in serum
      trace elements emphasize the need for monitoring trace elements in patients
      receiving maintenance dialysis.

PMID- 24749134
TI  - Temporary central line related thrombosis in a pediatric intensive care unit in
      central Saudi Arabia. Two-year incidence and risk factors.
AB  - OBJECTIVE: To estimate the incidence of temporary central venous line (CVL)
      related thrombosis among the pediatric population of critical care units, and to
      determine the possible predictors for developing CVL thrombosis. METHODS: A
      retrospective cohort study of patients </=14 years of age who were admitted to
      the pediatric intensive care unit (PICU) at King Abdulaziz Medical City, Riyadh,
      Saudi Arabia from 2009 to 2011 was performed. The patients were recruited using
      the PICU admission database, and the infection control unit database. RESULTS: In
      2 years, there were 1,361 admissions to the PICU. Only 248 patients required a
      central line for acute management. Twenty-one (8.5%) patients developed a
      thrombosis. The risk of thrombosis increased with multiple insertions of the
      central line compared with a single central line insertion (95% confidence
      interval: 2.339-16.667; p=0.0003). CONCLUSION: Among all predictors, the number
      of CVLs was the only significant predictor of CVL thrombosis. Patients with
      multiple CVLs are at 6.2 times higher risk of developing thrombosis compared with
      those with a single CVL.

PMID- 24749135
TI  - Ocular malignant tumors. Review of the Tumor Registry at a tertiary eye hospital
      in central Saudi Arabia.
AB  - OBJECTIVE: To present the epidemiologic profile and magnitude of ocular malignant
      tumors (MT) representative of the Saudi population from the Tumor Registry (TR)
      at King Khaled Eye Specialist Hospital (KKESH). METHODS: This study evaluated the
      demographic information, clinical features including tumor laterality, ocular
      tissue of origin, and diagnosis of patients from the TR registry between 1983 and
      2012 at KKESH, Riyadh, Kingdom of Saudi Arabia. The incidence of MT among Saudi
      adults (>/= 15 years old), and children (<15 years old) was estimated. RESULTS:
      The TR recorded 4,146 neoplasms (2,509 [60.5%] benign tumors, and 1,637 [39.5%]
      MT). The incidence of MT in children was 3.6 per million/year (M/Y), and 2.4/M/Y
      for adults. Retinoblastoma (Rb) (n=763, 91%) was the most common ocular
      malignancy in children. In adults, the most common MT was squamous cell carcinoma
      (SCC) (n=363, 45.8%), basal cell carcinoma (BCC) (n=186, 23%), uvealmelanoma
      (n=94, 11.9%), sebaceous gland carcinoma (n=54, 6.8%), lymphomas (orbital,
      adnexal) (n=46, 5.8%), and others (n=53, 6.8%). The Rb (7.7/M/Y in <5 years old
      Saudi children) was less frequent than that reported in some Gulf countries, but
      higher than that reported from the West. The SCC was less frequent in countries
      with comparable sun exposure than in other continents, but the incidence remained
      unchanged over 3 decades. There was a significant increase in BCC between 1983
      1992 and 2003-2012. CONCLUSION: The rates of all cancers remained stable over 3
      decades except BCC, which showed a significant rise.

PMID- 24749136
TI  - Early results of the proximal femoral nail antirotation-Asia for
      intertrochanteric fractures in elderly Chinese patients.
AB  - OBJECTIVE: To report early efficacy and safety of the proximal femoral nail
      antirotation-Asia for intertrochanteric fractures in elderly Chinese patients.
      METHODS: This retrospective study was carried out in the Second Hospital of Anhui
      Medical University, Anhui, China between June 2009 and December 2012. A total of
      108 patients with intertrochanteric fractures were available for the outcome
      analysis in the study. There were 62 female and 46 male patients with a mean age
      of 75 +/= 10 years. The stable group included 18 cases of 31 A1 fractures, the
      unstable group included 68 cases of 31 A2 fractures, and 22 cases of 31 A3
      fractures. Follow-up evaluations were performed at 1, 3, 6, 9, and 12 months, and
      every year thereafter. RESULTS: During the average 29 +/= 9 months early follow
      up period, 4 patients (4%) were lost, and 6 patients (6%) died within 6 months
      due to causes unrelated to the fracture. Fracture union occurred in all patients,
      83 patients (85%) showed an excellent, or good outcome. The mean Harris Hip Score
      was 85.2 +/= 7.5 points. Mechanical failures, such as bending, or breaking of the
      implant were not seen, and cut-outs were not observed. CONCLUSION: The results
      suggest that proximal femoral nail antirotation-Asia is effective and safe in the
      treatment of inter-trochanteric fractures in elderly Chinese patients.

PMID- 24749137
TI  - Impact of atopic dermatitis on the quality of life of Saudi children.
AB  - OBJECTIVE: To assess the impact of atopic dermatitis (AD) on the quality of life
      (QoL) of Saudi infants and children using a validated/culturally adapted Arabic
      version of the infants' dermatitis quality of life (IDQoL) index, and to
      investigate the correlation between IDQoL and disease severity. METHODS: This
      study was performed in the Dermatology Clinics and Hospitals affiliated to Qassim
      University, Buraidah, Saudi Arabia between September 2012 and August 2013. The
      study was designed to investigate the role of IDQoL in AD patients with different
      severities. The AD patients (n=630) were evaluated for IDQoL and disease severity
      using the SCORing of Atopic Dermatitis index. RESULTS: The average (+/=standard
      deviation) of IDQoL score was 12.3+/=5.1 for all studied subjects. The IDQoL
      scores were significantly different among the 3 studied severity groups, with a
      highest score in the severe group (p=0.000). A positive correlation was observed
      between the severity of AD and IDQoL scores (r=0.596, p=0.000). Three items with
      a negative impact on IDQoL were itching and scratching, the child's mood, and
      time to get the child to sleep. All these reached a significantly higher value in
      the severe group compared with the moderate or mild groups (p=0.000). No
      significant differences were observed concerning gender or the association with
      other atopic disorders (p=0.99, and p=0.79). CONCLUSION: This study demonstrates
      that AD manifestations impaired the IDQoL of Saudi patients and were also well
      correlated with the disease severity score.

PMID- 24749138
TI  - Relationship of the Arabic version of the asthma control test with ventilatory
      function tests and levels of exhaled nitric oxide in adult asthmatics.
AB  - OBJECTIVE: To determine the relationship between the asthma control test (ACT)
      score using the Arabic version, fractional exhaled nitric oxide (FENO), and lung
      functions, and to derive the cutoff points for the ACT score with the American
      Thoracic Society recommended FENO standard levels of inflammation control.
      METHODS: We recruited 59 adult asthmatics out of which 53 subjects completed the
      study between July 2011 and June 2012 at King Saud University, Riyadh, Saudi
      Arabia. The FENO levels were measured by NIOX MINO (Aerocrine AB, Solna, Sweden),
      and ventilatory functions were recorded by standard techniques. RESULTS: The FENO
      values were significantly higher in patients with an ACT score <20 (65.5+/= 35.4)
      compared with those patients with an ACT score >/= 20 (27.4+/=10.5, p<0.001).
      Among the well-controlled group based on the ACT score criteria, 6 (25%) cases
      had high FENO levels, while among the poorly controlled group, 23 (79.3%) cases
      had high FENO levels (odds ratio: 11.5; p<0.0001; confidence interval: 3.16
      41.72). There was a significant negative correlation between FENO and ACT score
      (r=-0.581, p<0.0001). At the international cutoff point of 20, the sensitivity
      was 95.2, and the specificity was 68.8. The receiver operating curve (ROC) showed
      that maximum sensitivity and specificity were observed at an ACT score cut off
      point of 19 (sensitivity: 90.5, and specificity: 81.2). CONCLUSION: The FENO
      levels correlate negatively with ACT scores however, the relationship between
      FENO and lung function is not significant. A significant relationship between ACT
      score and FENO levels indicate that there is an ongoing inflammatory state in
      patients with poor asthma control.

PMID- 24749139
TI  - Idiopathic hemihypertrophy.
AB  - Idiopathic hemihypertrophy is a congenital overgrowth disorder associated with an
      augmented risk for embryonal tumors. We present 4 cases of hemihypertrophy in
      Yemeni children living in Sana'a city. They presented to the outpatient clinics
      in a private hospital in Sana'a city, Yemen, over a period of 3 years from
      January 2009 to December 2011. The first 2 cases had no complaints apart from
      asymmetrical size of one side of their bodies (left side hemihypertrophy). The
      third case presented with left side hemihypertrophy and an abdominal mass, which
      upon referral to a cancer center was confirmed to be Wilms' tumor. The fourth
      case had overgrowth of the right leg and foot with polydactyly, and a right sided
      abdominal mass. He was diagnosed to have an ureteropelvic junction stricture with
      hydronephrosis and absent left kidney.

PMID- 24749140
TI  - Is vesicolithotomy with bladder wash the answer for rectovesical fistula
      secondary to neglected vesical stone? Complicated presentation but simple
      management.
AB  - It is extremely rare that the urinary bladder stones cause vesicorectal fistulas.
      Urinary tract infection and poor fluid intake are the main etiologies that
      precipitate vesical stone formation, and subsequent rectovesical fistula. We
      present a complicated case of neglected vesical stone, which recurred 3 times.
      The patient presented with passage of urine per rectum leading to fecal
      incontinence. He was managed only with vesicolithotomy and bladder wash with
      eventual spontaneous closure of the rectovesical fistula.

PMID- 24749141
TI  - Winging of the scapula.

PMID- 24749142
TI  - The diagnostic utility of mean platelet volume and red cell distribution width in
      active Crohn's disease and intestinal tuberculosis.

PMID- 24749143
TI  - Analysis of an early intervention tibial component for medial osteoarthritis.
AB  - Tibial component loosening is an important failure mode in unicompartmental knee
      arthroplasty (UKA) which may be due to the 6-8 mm of bone resection required. To
      address component loosening and fixation, a new early intervention (EI) design is
      proposed which reverses the traditional material scheme between femoral and
      tibial components. The EI design consists of a plastic inlay for the distal femur
      and a thin metal plate for the proximal tibia. With this reversed materials
      scheme, the EI design requires minimal tibial bone resection compared with
      traditional UKA. This study investigated, by means of finite element (FE)
      simulations, the advantages of a thin metal tibial component compared with
      traditional UKA tibial components, such as an all-plastic inlay or a metal-backed
      onlay. We hypothesized that an EI tibial component would produce comparable
      stress, strain, and strain energy density (SED) characteristics to an intact knee
      and more favorable values than UKA components, due primarily to the preservation
      of dense cancellous bone near the surface. Indeed, FE results showed that
      stresses in the supporting bone for an EI design were close to intact, while
      stresses, strains, and strain energy densities were reduced compared with an all
      plastic UKA component. Analyzed parameters were similar for an EI and a metal
      backed onlay, but the EI component had the advantage of minimal resection of the
      stiffest bone. 

PMID- 24749145
TI  - Skill building: assessing the evidence.
AB  - OBJECTIVE: Skill building for adults involves multiple approaches to address the
      complex problems related to serious mental illness. Individuals with
      schizophrenia are often the research focus. The authors outline key skill
      building approaches and describe their evidence base. METHODS: Authors searched
      meta-analyses, research reviews, and individual studies from 1995 through March
      2013. Databases surveyed were PubMed, PsycINFO, Applied Social Sciences Index and
      Abstracts, Sociological Abstracts, Social Services Abstracts, Published
      International Literature on Traumatic Stress, ERIC, and CINAHL. Authors chose
      from three levels of evidence (high, moderate, and low) on the basis of
      benchmarks for the number of studies and quality of their methodology. They also
      described the evidence of service effectiveness. RESULTS: Over 100 randomized
      controlled trials and numerous quasi-experimental studies support rating the
      level of evidence as high. Outcomes indicate strong effectiveness for social
      skills training, social cognitive training, and cognitive remediation, especially
      if these interventions are delivered through integrated approaches, such as
      Integrated Psychological Therapy. Results are somewhat mixed for life skills
      training (when studied alone) and cognitive-behavioral approaches. The
      complexities of schizophrenia and other serious mental illnesses call for
      individually tailored, multimodal skill-building approaches in combination with
      other treatments. CONCLUSIONS: Skill building should be a foundation for
      rehabilitation services covered by comprehensive benefit plans that attend to the
      need for service packages with multiple components delivered in various
      combinations. Further research should demonstrate more conclusively the long-term
      effectiveness of skill building in real-life situations, alone and in various
      treatment combinations. Studies of diverse subpopulations are also needed.

PMID- 24749144
TI  - Evaluation of meniscal mechanics and proteoglycan content in a modified anterior
      cruciate ligament transection model.
AB  - Post-traumatic osteoarthritis (PTOA) develops as a result of traumatic loading
      that causes tears of the soft tissues in the knee. A modified transection model,
      where the anterior cruciate ligament (ACL) and both menisci were transected, was
      used on skeletally mature Flemish Giant rabbits. Gross morphological assessments,
      elastic moduli, and glycosaminoglycan (GAG) coverage of the menisci were
      determined to quantify the amount of tissue damage 12 weeks post injury. This
      study is one of the first to monitor meniscal changes after inducing combined
      meniscal and ACL transections. A decrease in elastic moduli as well as a decrease
      in GAG coverage was seen.

PMID- 24749146
TI  - Subacute thyroiditis metamorphosing into Graves' disease.

PMID- 24749147
TI  - Complete cardiac rupture associated with closed chest cardiac massage: case
      report and review of the literature.
AB  - Chest skeletal injuries are the most frequent complications of external chest
      massage (ECM) during cardiopulmonary resuscitation, but heart and great vessels
      lacerations that are indeed very rare. We report the case of a 35-year-old
      workman who collapsed and underwent ECM by his co-workers for almost 30 min. At
      autopsy, no external injuries, fractures or bruises of the ribs or sternum, were
      observed. A hemopericardium with a rupture of the heart was found, with no signs
      of pre-existent cardiac disease. Bruises of thoracic aortic wall, lung petechiae,
      a contusion of the liver, and bruises of lumbar muscles were found. The cause of
      death was due to sudden cardiac death with an extensive cardiac rupture. This is
      an unusual report of massive heart damage without any skeletal or muscle chest
      injuries, secondary to cardiopulmonary resuscitation. This kind of cardiac
      lesions may be considered when thoracic-abdominal trauma, or medical history, is
      unclear.

PMID- 24749148
TI  - Psychosocial complications of Crohn's disease and cause of death.
AB  - Patients who suffer from Crohn's disease are prone not only to the complications
      of a relapsing, unpredictable disease, but also to feelings of stigmatization;
      depression; and increased risk of suicidal ideation, suicide, or drug and alcohol
      abuse. Cases performed at the Jackson County Medical Examiner's Office from 2008
      to 2010 were reviewed. Autopsy findings, investigator reports, toxicology
      results, medical records, and interviews with survivors were analyzed. Twelve
      cases of Crohn's disease were recovered. In 10 of these cases, inflammatory bowel
      disease was not the cause of death. Instead, psychosocial consequences of the
      disease had significant implications in the deaths. The mean age of decedents was
      45 years, with a female predominance. In eight cases, the decedents lived alone.
      Five patients had issues of acute or chronic drug or alcohol use. Five patients
      committed suicide. These cases underscore the role of psychosocial factors that
      can contribute significantly to the cause of death in patients with Crohn's
      disease.

PMID- 24749149
TI  - Reply to 'State of the art in research into the risk of low dose radiation
      exposure'.

PMID- 24749150
TI  - Progress towards personalized medicine for ameloblastoma.
AB  - Ameloblastoma is a locally infiltrative benign odontogenic neoplasm. Tumours may
      be large, destructive and recurrent, requiring radical surgery with associated
      facial deformity and morbidity. The molecular pathogenesis of this tumour has
      been unclear, retarding the development of non-invasive gene-targeted therapies.
      In a recent paper in this journal, Kurppa et al. [4] showed that EGFR-targeted
      therapy blocked cell proliferation in an ameloblastoma primary cell culture. That
      this therapy was not effective in another primary cell culture led to the
      discovery of the oncogenic BRAF V600E mutation in a high proportion (63%) of
      ameloblastoma samples. By defining two separate pathways, both of which can be
      specifically targeted, these findings are an important step towards personalized
      medicine of ameloblastoma. We discuss the findings in the broader context of
      ameloblastoma, as well as the effects of tumour microenvironment and molecular
      heterogeneity that need to be taken into account when considering the use of
      personalized therapies based on specific genetic mutations in individual
      patients.

PMID- 24749151
TI  - Open access under scrutiny.

PMID- 24749152
TI  - The past and future habitability of planet Mars.

PMID- 24749153
TI  - The selection of parameter values in studies of environmental radiological
      impacts.

PMID- 24749154
TI  - Reply to 'The selection of parameter values in studies of environmental
      radiological impacts'.

PMID- 24749156
TI  - Michael Nitabach.

PMID- 24749155
TI  - Radiation dosimetry assessment of routine CT scanning protocols used in Western
      Australia.

PMID- 24749157
TI  - Reply to 'Radiation dosimetry assessment of routine CT scanning protocols used in
      Western Australia'.

PMID- 24749158
TI  - On the definition of the ICRP reference 'Brown Seaweed' implemented in the ERICA
      software.

PMID- 24749159
TI  - Late diagnosis and HIV infection in children attending a service of specialized
      care for pediatric AIDS in Brazil.
AB  - INTRODUCTION: This study describes the frequency of late diagnosis and HIV among
      children attending a pediatric AIDS clinic. METHODS: Cross-sectional study in
      children exposed to HIV from 2005-2008. A questionnaire was given that included
      questions on demographics and clinical information. RESULTS: Two-hundred twenty
      one (97.8%) children were exposed to HIV during pregnancy/childbirth. A total of
      193 (87.3%) children had late enrolment in the service and late access to HIV
      serology. The frequency of HIV was 21.3% (95% confidence interval [CI] 15.9%
      26.7%). Protective factors were earlier diagnosis [odds ratio (OR)=0.17 (0.08
      0.37)] and receiving complete prophylaxis [OR=0.29 (0.09-0.97)]; being born by
      vaginal delivery was a risk factor [OR=4.45 (1.47-13.47)]. CONCLUSIONS: There was
      a high frequency of late diagnosis in this patient cohort. Earlier diagnosis is
      an important measure for controlling HIV among children.

PMID- 24749161
TI  - Reasons behind Greek problem drug users' decisions  to quit using drugs and
      engage in treatment of their  own volition: sense of self and the Greek filotimo.
AB  - AIMS: The aim of this study was to explore Greek problem drug users' perceptions
      of the reasons that led them to quit using drugs and engage in treatment of their
      own volition. DESIGN: Qualitative semi-structured in-depth interviews. SETTING:
      Two state drug agencies in Thessaloniki, Greece. PARTICIPANTS: A total of 40
      adult problem drug-using men and women participated in the study. MEASUREMENTS:
      Participants were asked to reflect on their decisions to wean themselves from
      drugs and enter treatment. Findings Participants reported that their decisions
      centred on the re-conceptualization of the drug-using community and their
      membership in it, the desire to restore aspects of identities thatwere deemed to
      be spoiled, and finally memories of their drug-free selves. The importance of the
      distinctively Greek notion of filotimo in this discussion is highlighted.
      CONCLUSIONS: Primarily in relation to filotimo (a concept that represents a
      complex array of virtues that regulates behaviour towards one's family), the
      desire to restore one's spoiled identity plays a pivotal role in Greek problem
      drug users' decisions to cease drug use and engage in treatment.

PMID- 24749160
TI  - Efficacy of stimulants for cognitive enhancement in  non-attention deficit
      hyperactivity disorder youth:  a systematic review.
AB  - BACKGROUND AND AIMS: Increasing prescription stimulant abuse among youth without
      diagnoses of attention deficit hyperactivity disorder (ADHD) is of concern. The
      most frequently cited motive for abuse is improved academic achievement via
      neurocognitive enhancement. Our aim in reviewing the literature was to identify
      neurocognitive effects of prescription stimulants in non-ADHD youth. METHODS: A
      systematic review was conducted for youth aged 12-25 years using Preferred
      Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.
      Fourteen papers were included. RESULTS: Modafinil appears to improve reaction
      time (P <= 0.04), logical reasoning (P <= 0.05) and problem-solving.
      Methylphenidate appears to improve performance in novel tasks and attention-based
      tasks (P <= 0.05), and reduces planning latency in more complex tasks (P <=
      0.05). Amphetamine has been shown to improve consolidation of information (0.02
      >= P <= 0.05), leading to improved recall. Across all three types of prescription
      stimulants, research shows improved attention with lack of consensus on whether
      these improvements are limited to simple versus complex tasks in varying youth
      populations. CONCLUSIONS: The heterogeneity of the non-attention deficit
      hyperactivity disorder youth population, the variation in cognitive task
      characteristics and lack of replication of studies makes assessing the potential
      global neurocognitive benefits of stimulants among non-attention deficit
      hyperactivity disorder youth difficult; however, some youth may derive benefit in
      specific cognitive domains.

PMID- 24749162
TI  - Clinical and diagnostic imaging characteristics of lateral digital flexor
      tendinitis within the tarsal sheath in four horses.
AB  - Lateral digital flexor tendonitis is a rarely reported cause of hind limb
      lameness in performance horses. The purpose of this retrospective study was to
      describe clinical and diagnostic imaging findings for a group of horses with
      lateral digital flexor tendinitis within the tarsal sheath. Equine cases with a
      diagnosis of lateral digital flexor tendonitis and magnetic resonance imaging
      (MRI) studies of the affected region were retrieved from North Carolina
      University's medical record database. Recorded data for included horses were
      signalment; findings from history, physical examination, lameness examination,
      and all diagnostic imaging studies; treatment administered; and outcome. Four
      horses met inclusion criteria. Lameness was mild/moderate in severity and
      insidious in onset in all patients. Responses to flexion tests were variable. All
      horses showed positive improvement(70-90%) in lameness after tarsal sheath
      analgesia. Radiographic, scintigraphic, and ultrasonographic findings were
      inconclusive. For all horses, MRI characteristics included increased T2, PD, and
      STIR signal intensity within the lateral digital flexor tendon in the area of the
      tarsal sheath. Tarsal sheath effusion was slight in three horses, and
      mild/moderate in one horse. With medical treatment, two horses were sound at 6
      month follow up, one horse was sound at 1-year followup, and one horse had a
      slight persistent lameness (grade 1/5) at 9-month followup. Findings supported
      the use of MRI for diagnosing lateral digital flexor tendonitis within the tarsal
      sheath in horses. Affected horses may have a good prognosis for return to
      athletic performance following appropriate medical treatment.

PMID- 24749163
TI  - Antidepressant use among survivors of childhood, adolescent and young adult.

PMID- 24749164
TI  - Ruptured anterior mitral leaflet aneurysm in aortic valve infective endocarditis-
      evaluation by three-dimensional echocardiography.
AB  - Ruptured aneurysm of the anterior mitral leaflet is a rare but a devastating
      complication secondary to aortic valve infective endocarditis. We report a case
      of 30-year-old male with native aortic valve endocarditis who was referred to us
      for evaluation of worsening of heart failure after an initial period of
      responsiveness to antibiotics. Detailed evaluation with two-dimensional and three
      dimensional transthoracic echocardiography revealed ruptured anterior mitral
      leaflet aneurysm with severe eccentric mitral regurgitation along with a large
      vegetation on the aortic valve. The patient underwent successful surgical closure
      of the defect along with aortic valve replacement.

PMID- 24749165
TI  - Spiral hypertrophic cardiomyopathy as detected by cardiac magnetic resonance.
AB  - Hypertrophic cardiomyopathy (HCM) is a genetically determined heart muscle
      disease; characterized by left ventricular hypertrophy (LVH). Spiral HCM is
      described as having a counterclockwise rotation pattern of hypertrophy along with
      variable degrees of fibrosis. A 34-year-old female presented with symptoms
      suggestive of heart failure. Echocardiography showed concentric LVH with normal
      contractility. Cardiac MRI showed asymmetric septal hypertrophy with mid-cavity
      obliteration and a spiral pattern of variably increasing wall thickness. Late
      gadolinium enhancement (LGE) demonstrated several areas of abnormal
      postgadolinium uptake. We report a case of spiral HCM. We should consider
      cardiovascular magnetic resonance (CMR) as the reference standard for diagnosing
      HCM.

PMID- 24749166
TI  - Spontaneous bacterial coronary sinus septic thrombophlebitis treated successfully
      medically.
AB  - A 38-year-old farmer was hospitalized for fever, chills, cough, and chest pain
      lasting for 7 days. Due to persistent symptoms, patient was referred to hospital.
      Blood cultures identified oxacillin-sensitive Staphylococcus aureus (OSSA).
      Transthoracic echocardiography (TTE) showed large pericardial effusion, a mobile
      heterogeneous mass originating from the coronary sinus ostium, no sign of
      valvular endocarditis. Pericardiocentesis was done carrying out purulent fluid,
      microbiological culture isolating an OSSA. Parenteral penicillin M was
      administered for 6 weeks. At the end of this antibiotherapy regimen, TTE showed
      no coronary sinus mass with complete vacuity of the coronary sinus vein and no
      pericardial effusion.

PMID- 24749167
TI  - The pyramid of danger: the value of TEE in detecting risk of aortic perforation
      during TAVI.
AB  - An 87-year-old man undergoing transcatheter aortic valve implantation (TAVI) for
      severe aortic stenosis was noted to have bulky calcification of the noncoronary
      aortic cusp, extending into the corresponding sinus, on transesophageal
      echocardiography (TEE). During balloon valvuloplasty, TEE demonstrated
      displacement of this calcium into the aortic wall, producing a distinctive
      pyramidal indentation and indicating threatened focal aortic perforation.
      Importantly, this hazard was not evident on corresponding x-ray cine-angiography
      and emphasizes the value of TEE in guiding TAVI procedures. This information
      allowed alteration in deployment technique for the TAVI valve and forewarned the
      team to increased risk of a major hazard at this stage.

PMID- 24749168
TI  - CardioPulse. Radiation awareness: an appeal is made for including radiation
      exposure in a patient's medical records.

PMID- 24749169
TI  - CardioPluse. Radiation exposure to personnel in cardiac catheterization
      laboratories: an English summary of a published manuscript where radiation
      exposure in the cath lab was measured by the lead author Dr Heiner von Botticher
      catheterization laboratories.

PMID- 24749170
TI  - CardioPulse. Radiation exposure and the risk of cancer for interventional
      cardiologists and electrophysiologists.

PMID- 24749172
TI  - Nursing must be a graduate profession (Well, he would say that, wouldn't he!).
      Editorial response.

PMID- 24749171
TI  - Validation of patient specific surgical guides in total hip arthroplasty.
AB  - BACKGROUND: The validation of patient-specific surgical guides (PSGs) by their
      design and the comparison of planned and actual PSG setting in total hip
      arthroplasty (THA) have not previously been reported. METHODS: The errors between
      preoperative planning and computed tomography (CT)-based PSG setting (E1), and
      between preoperative planning and implantation (E2) were evaluated using CT in 16
      fresh cadaveric hips. RESULTS: E2 was significantly smaller with the wide-base
      contact resurfacing-THA PSG than with the narrow-base-contact type (P<0.05).
      E1/E2 of the wide-base-contact neck-cut PSG was 1.6+/-0.7 degrees /2.4+/-1.1
      degrees  for the coronal plane and 1.2+/-0.8 mm/0.7+/-0.5mm for the medial neck
      cut height. E1/E2 of the wide-base-contact cup-impaction PSG was 1.0+/-0.9
      degrees /3.4+/-1.9 degrees  for inclination and 1.7+/-1.1 degrees /6.6+/-4.4
      degrees  for anteversion. CONCLUSIONS: The wide-base-contact PSG in resurfacing
      THA and the PSG for neck-cut in THA could be applied clinically. Although cup
      impaction PSG setting was acceptable, errors were made due to the impaction
      process during cup implantation.

PMID- 24749174
TI  - Palpitations.  The heart of the problem.

PMID- 24749173
TI  - Pathways to Alzheimer's disease.
AB  - Recent trials of anti-amyloid agents have not produced convincing improvements in
      clinical outcome in Alzheimer's disease; however, the reason for these poor or
      inconclusive results remains unclear. Recent genetic data continue to support the
      amyloid hypothesis of Alzheimer's disease with protective variants being found in
      the amyloid gene and both common low-risk and rare high-risk variants for disease
      being discovered in genes that are part of the amyloid response pathways. These
      data support the view that genetic variability in how the brain responds to
      amyloid deposition is a potential therapeutic target for the disease, and are
      consistent with the notion that anti-amyloid therapies should be initiated early
      in the disease process.

PMID- 24749175
TI  - Health tips.  Help for someone grieving a death.

PMID- 24749176
TI  - Oral hygiene and reduced throat cancer risk.

PMID- 24749177
TI  - Europeans give dark chocolate healthy status.

PMID- 24749178
TI  - Obesity surgery. New approaches.

PMID- 24749179
TI  - Chronic cough.  When nothing works.

PMID- 24749180
TI  - Nausea after surgery.  Prevention, management.

PMID- 24749181
TI  - I usually avoid drinking water on airline flights because it's a hassle to go to
      the bathroom.  My husband says I need to drink water to avoid getting dehydrated.
      Any advice?

PMID- 24749182
TI  - Why does vision in dim lighting or nighttime situations get worse as you get
      older?

PMID- 24749183
TI  - Mentorship--a two-way exchange.

PMID- 24749184
TI  - Mobile health: We've got an app for that!

PMID- 24749185
TI  - Author responds.

PMID- 24749186
TI  - Over the course of our careers we will see many thousands of patients.

PMID- 24749187
TI  - The future hospital--implications for acute care.

PMID- 24749188
TI  - ST elevation in ECG lead aVR signals severe acute left main coronary artery
      disease.

PMID- 24749190
TI  - Acute physicians should take the lead in developing acute kidney injury services
      in district general hospitals.

PMID- 24749189
TI  - Pulmonary embolism in pregnancy.

PMID- 24749191
TI  - Validation of enhanced stabilization of municipal solid waste under controlled
      leachate recirculation using FTIR and XRD.
AB  - Leachate recirculation at neutral PH accompanied with buffer/nutrients addition
      has been used successfully in earlier stabilization of municipal solid waste in
      bioreactor landfills. In the present study, efforts were made to enhance the
      stabilization rate of municipal solid waste (MSW) and organic solid waste (OSW)
      in simulated landfill bioreactors by controlling the pH of recirculated leachate
      towards slightly alkaline side in absence of additional buffer and nutrients
      addition. Enhanced stabilization in waste samples was monitored with the help of
      analytical tools like Fourier Transform Infrared Spectroscopy (FTIR) and X-Ray
      Diffraction (XRD). Predominance of bands assigned to inorganic compounds and
      comparatively lower intensities of bands for organic compounds in the FTIR
      spectra of waste samples degraded with leachate recirculation under controlled pH
      confirmed higher rate of biodegradation and mineralization of waste than the
      samples degraded without controlled leachate recirculation. XRD spectra also
      confirmed to a greater extent of mineralization in the waste samples degraded
      under leachate recirculation with controlled pH. Comparison of XRD spectra of two
      types of wastes pointed out higher degree of mineralization in organic solid
      waste as compared to municipal solid waste.

PMID- 24749192
TI  - Water-sediment flow models for river reaches sediment related pollution control.
AB  - Hybrid water-sediment flow models for river reaches have been for predicting
      sediment and sediment related pollutions in water courses. The models are
      developed by combining sediment rating model and the Muskingum model applicable
      for a reach. The models incorporate sediment concentration and water discharge
      variables for a river reach; allow defining downstream sediment rating curve in
      terms of upstream water discharges. The model is useful in generating sediment
      concentration graph for a station having no water discharge records. The hybrid
      models provide forecasting forms that can be used to forecast downstream sediment
      concentration/water discharges 2kx time unit ahead. The forecasting models are
      useful for applications in real time namely, in the real time management of
      sediment related pollution in water courses and in issuing flood warning.
      Integration of sediment rating model and the Muskingum model increases model
      parameters and nonlinearity requiring efficient estimation technique for
      parameter identification. To identify parameters in the hybrid models genetic
      algorithm (GA) based optimization technique can be used. The new model relies on
      the Muskingum model, obey continuity requirement and the parameters can be used
      in the Muskingum model with water discharges to estimate/predict downstream water
      discharge values. The proposed model formulations are demonstrated for simulating
      and forecasting sediment concentration and water discharges in the Mississippi
      River Basin, USA. Model parameters are estimated using non-dominated sorting
      Genetic Algorithm II (NSGA-II). Model results show satisfactory model
      performances.

PMID- 24749193
TI  - Studies on adsorption of nickel on sand from constructed wetland and effect of
      leaching agents.
AB  - The present study chronicles experiments done on the feasibility of exploiting
      sand's natural capacity as an adsorbant for the removal of nickel laden
      wastewater. Batch adsorbtion studies were carried out. Leaching agents such as
      0.01 M EDTA (disodium salt), 0.1 N HCI and acetic acid alongwith water as control
      showed 0.01 M EDTA-Na and 0.1 N HCl as suitable leaching agents to enhance metal
      removal from sand. Pot experiments were successively carried out with Arundo
      donax plants to determine the effectiveness of treatment on the sand. It was
      found that sand could continue as a good substrate for plant growth and the
      amount of leaching agent required for a pilot scale constructed wetland was
      estimated. The maximum amount of nickel adsorbed was 5 mg/L at a pH of 6. EDTA
      was selected as the chelating agent and the pot experiments showed no immediate
      effects on plant growth.

PMID- 24749194
TI  - The role of hydrothermally prepared supported photocatalytic composite in organic
      micro-pollutants removal from the water.
AB  - This work deals with the non-biodegradable micro-pollutants degradation by
      supported photocatalyst based heterogeneous photocatalytic reaction. TiO2 based
      supported photocatalyst was prepared by the hydrothermal technique to improve the
      photocatalytic performance along with easy recovery of suspended photocatalyst
      from aqueous medium after photoreaction. TO2 deposited calcium alumino-silicate
      beads (CASB) supports were prepared under mild hydrothermal conditions
      (Temparature-200 degrees C, Duration-24 h). In the present study, industrial dyes
      such as Amaranth and Brilliant Yellow were used as model micro-pollutants in
      aqueous solution. A real time pesticide industrial effluent was tested for its
      photocatalytic removal of organic pollutants using TO2 deposited CASB supported
      photocatalytic composite as an effective photocatalyst. Photocatalytic
      degradation of micro-pollutants present in aqueous medium was carried out in a
      batch photoreactor, at atmospheric pressure and temperature (28 degrees C). The
      influence of different light sources, irradiation time, catalyst load and
      catalytic performance is discussed. The photocatalytic degradation of micro
      pollutants in aqueous medium was evaluated by determination of COD and %T. Easy
      separation and recovery of suspended photocatalysts from aqueous solution is the
      major advantage of hydrothermally prepared supported photocatalytic composite.

PMID- 24749195
TI  - Biological decolourisation of pulp mill effluent using white rot fungus Trametes
      versicolor.
AB  - The conventional biological treatment methods employed in the pulp and paper
      industries are not effective in reducing the colour and chemical oxygen demand
      (COD). The white-rot fungi are reported to have the ability to biodegrade the
      lignin and its derivatives. This paper is focused on the biological treatment of
      pulp mill effluent from a bagasse-based pulp and paper industry using fungal
      treatment. Experiments were conducted using the white rot fungus, Trametes
      versicolor in shake flasks operated in batch mode with different carbon sources.
      The decolourisation efficiencies of 82.5% and 80.3% were obtained in the presence
      of 15 g/L and 5 g/L of glucose and sucrose concentrations respectively with a
      considerable COD reduction. The possibility of reusing the grown fungus was
      examined for repeated treatment studies.

PMID- 24749196
TI  - Remediation of acidic industrial effluents by sulphate reducing bioreactors.
AB  - This research work was designed to examine the feasibility of sulphate reducing
      bioreactors with organic substrates, containing manures, and other cellulosic
      wastes for remediation of acidic industrial wastewater on bench scale. The pH of
      the wastewater increased from 5.5. to 7.18, alkalinity from 0 to 2566 mg/L as
      CaCO3, acidity removal was from 357 to 210 mg/L as CaCO3, sulphate removal was
      92.7%, lead removal was 97.3%, zinc- 99.8%, copper-97.5%, cobalt-99.4%, manganese
      98.9%, nickel- 98.3% and iron 99.5%, were observed in this study after the
      maximum retention of 106 days. This paper describes bioremediation as a state-of
      art for the treatment of wastewater from the industries.

PMID- 24749197
TI  - Column chromatographic separation of lead(II) using poly [dibenzo-18-crown-6] in
      L-ascorbic acid.
AB  - A column chromatographic separation method has been developed for separation of
      Lead(II) using poly[dibenzo-18-crown-6]. The separation was carried out in L
      ascorbic acid medium. The adsorption of Lead(II) was quantitative from 1 x 10(-2)
      M to 1 x 10(-7) M L-ascorbic acid. The capacity of poly [dibenzo-18-crown-6] for
      Lead (II) was found to be 0.530 +/- 0.01 mmol/g of crown polymer. Lead(II) was
      separated from commonly associated metal ions such as Mg(II), Co(II), Ni(II),
      Cd(II), Mn(II) Th(IV) and U(VI) and other associated metal ions in binary as well
      as in multicomponent mixtures. The sorption of Lead was carried out in presence
      of various ions to ascertain the tolerance limits of individual. The method was
      extended for the determination of Lead in real samples. The method is simple,
      rapid and selective having good reproducibility (approximately +/- 2%).

PMID- 24749198
TI  - Potentiometric studies of metal-biomass interaction with reference to
      bioaccumulation.
AB  - An electrochemical experiment (Linear Polarization) has been carried out to
      illustrate the binding of Cd2+ and Pb2+ by Moringa oleifera seed powder.
      Reduction in Open Circuit Potential (OCP) value indicates a decrease in the metal
      concentration due to the binding of metal ions at the active sites of biomass.
      Maximum sorption of Cd2+ and Pb2+ was calculated by the use of Nernst equation
      and found to be 81.85 and 85.45% respectively.

PMID- 24749199
TI  - Effects of various agro-industrial residues on soil fertility and yield and
      quality of potatoes.
AB  - Nine combinations of production residues of agro-industries, urban wastes and
      mineral fertilizers were applied to potatoes (Solanum tuberosum var. Marabel) in
      a field experiment, and the effect of these combinations on soil characteristics,
      on yield and on various quality parameters of tubers were determined. The
      applications significantly affected soil pH, CaCO3 and organic matter content.
      Total N and available P and K levels of soils showed significant differences
      between the applications. The content of available Zn and Mn in the soil differed
      significantly between the applications. Sufficient levels of N, P and K were not
      attained in leaves in any application. Significant differences were observed
      between the P content of the leaves of the control and of the other applications.
      Potassium and Na content of the leaves showed significant variations between the
      applications. Manganese was at a statistically higher level in the leaves of some
      combinations. The nitrogen, P and Mn contents of tubers differed significantly
      between the applications. Phosphorus, K, Mg and Cu levels were found to be
      sufficient, but Fe, Zn and Mn were low in tubers. Tuber yield was statistically
      highest in the Wastes P + Mineral NK combination. Reduced sugar and protein
      content of the tubers was affected significantly by the applications. Significant
      correlations were found between soil, leaf and tubers.

PMID- 24749200
TI  - Assessment of real time traffic noise attenuation by tree belts within Kolkata
      city (India).
AB  - The study of the existing scenario of the effect of trees and shrubs as urban
      screen plantings for abating the level of real time traffic-induced noise
      pollution in Kolkata city deserves extreme importance. However, no such data are
      available till date in this area. This paper reports the result of a preliminary
      study to assess the attenuation of real time traffic noise by tree belts at three
      different important locations of the city. This measurement provides some new and
      interesting data which will be useful for further study and subsequent plan.

PMID- 24749201
TI  - Evaluation studies of noise and air pollution during festival seasons in India.
AB  - The present research work is based on assessment of noise levels and ambient air
      quality at selected locations during festival seasons in Nagpur city. The noise
      levels were exceeding the permissible limits almost at every location during the
      festival period. The huge emissions of smoke arising out bursting of firecrackers
      have significantly resulted into air pollution; particularly in terms of Sulphur
      Dioxide (SO2) and Respirable Suspended Particulate Matter (Fine Dust). The
      immediate effect of increasing noise levels is impairing of hearing that may
      cause auditory fatigue and finally lead to deafness.

PMID- 24749202
TI  - Study of noise pollution for three consecutive years during Deepawali festival in
      Meerut City, Uttar Pradesh (India).
AB  - The present paper deals with monitoring of noise pollution at different places of
      Meerut City (India) on the night of Deepawali festival. During the present study
      the noise levels were measured with the help of sound meter. The noise pollution
      is decreasing considerably for the last three years and it is recorded minimum in
      2009 as compared to 2008 and 2007. The main reason of this decrement is the
      growing environmental awareness in the people of Meerut City. Needless to say,
      students of most of the school in Meerut City now prefer to celebrate Deepawali,
      festival of lights without sound and smoke. The campaign for eco-friendly
      Deepawali is expected to catch on with people in Meerut City which has already
      demonstrated its commitment towards environment conservation. Mainly fire
      crackers are used during Deepawali. The present paper is an attempt to create
      awareness among the people of Meerut City about the bitter truth of fire
      crackers.

PMID- 24749203
TI  - Physico-chemical quality of drinking water in villages of Primary Health Centre,
      Waghodia, Gujarat (India).
AB  - 16 water samples were collected to study the physical and chemical quality of
      water of main source of drinking water in the villages of Primary Health Centre,
      Waghodia of Vadodara district of Gujarat. The values recommended by Indian
      Standard for Drinking Water (IS 10500:1991) were used for comparison of observed
      values. The study indicates that the contamination problem in these villages is
      not alarming at present, but Waghodia being industrial town, ground water quality
      may deteriorate with passage of time, which needs periodical monitoring. The
      study provides the local area baseline data which may be useful for the
      comparison of future study.

PMID- 24749204
TI  - Assessment of well-water quality for drinking purpose--a case study in Nari area,
      Nagpur District, Maharashtra (India).
AB  - The water from 20 wells of Nari area was assessed for different quality
      parameters. The nitrate (NO(-)3) concentration ranged from 57 to 80 ppm which is
      above the BIS limit while nitrite (NO(-02) concentration was within the BIS limit
      of 0.02 ppm. The pH of the water samples varied from 7.3 to 8.2. The
      concentrations of micronutrient cations, namely Zn, Fe, Cu and Mn, were below the
      toxic level in all the samples but some of the samples of the water had high and
      infinite growth of E. coli, Coliform bacteria, Pseudomonas aerugilosa, Yeast and
      molds count makes the well water of poor quality for drinking purpose.

PMID- 24749205
TI  - Turning refuse into resource: a study on aerobic composting.
AB  - The management of solid waste disposal had been a perennial problem every where
      in our country. In order to overcome this problem one possible solution is to
      compost the solid waste in the presence of air, so that it may be converted into
      an useful manure. With this intention, solid wastes like coir waste and water
      hyacinth had been collected and composted with the addition of cow dung. The
      composted material had been examined for the physical and chemical parameters.
      The content of macronutrients was found to be higher as the period of composting
      increased. There were gradual variations in the case of other parameters. A
      comparative account of the two types of solid waste is also given.

PMID- 24749206
TI  - Recycling of lime sludge emanating from tannery industry through vermicomposting
      using Eisenia foetida.
AB  - The research was focused on the control of pollution, which is caused due to
      tannery waste disposal, through the process of vermicomposting. Earthworms have
      increasingly been used for waste management. Therefore, the main aim of this
      study was to recycle the lime sludge emanating from a selected tannery industry
      through vermicomposting. Tannery solid waste was allowed to compost for 60 days,
      and then the composts were harvested and analyzed for selected physio-chemical
      and biochemical parameters. A flowering plant namely Tagets erecta Linn was grown
      in soil mixed with the vermicomposts obtained, and was studied for its growth
      attributes and compared with the control plant growth on soil alone. The
      attributes studied were biometric parameters, like root length, shoot length,
      plant height, plant weight, number of leaves, flowers and buds. The alkaline
      nature of the lime sludge was reduced to neutral range on vermicomposting. The
      electrical conductivity of the lime sludge was also reduced on vermicomposting
      which might be due to the transformation of complex organic compounds into
      simpler forms. The biochemical parameters, such as nitrogen and carbon were also
      reduced on vermicomposting.

PMID- 24749207
TI  - Effect of dietary Spirulina level on growth and chemical composition of carcass
      in rohu, Labeo rohita (Hamilton).
AB  - An experiment was conducted in three different tanks for 45 days (T1, T2 and T3)
      to investigate the effect of dietary Spirulina level on growth and chemical
      composition of carcass in rohu, Labeo rohita. A diet having de-oiled rice
      bran(30%), rice polish (15%), de-oiled mustard oil cake(25%), Soya bean oil
      cake(10%) and de-oiled groundnut cake(20%) was provided to the control (i.e. 100%
      formulated feed), whereas in T2 95% formulated feed with 5% Spirulina and in T3
      90% formulated feed with 10% Spirulina. Data were analysed with ANOVA (P < 0.05)
      and found significant. There was significant difference in the average final
      weight of the fish among treatments with highest in the T3 (11.28g) followed by
      T2 (8.32g) and T1 (7.51g). The higher SGR was recorded in T3 (2.17) followed by
      T2 (1.52) and T1 (1.28). There was significant difference in the average carcass
      composition of the fish among treatments with highest level in T3 followed by T2
      and T1.

PMID- 24749208
TI  - Role of antioxidants in detoxification of Cr (VI) toxicity in laboratory rats.
AB  - Cr(VI) compounds are highly toxic for biological system. These compounds are
      approximately 100 times more toxic than Cr(III) salts. Cr(VI) penetrates all
      membranes without any difficulty, while being unable to bind proteins. However,
      Cr(VI) has to reduce inside the cell to Cr(III) and produces ROS which causes LP,
      DNA damage, deplete sulfyhydryl and also alter calcium (Ca) and sodium (Na)
      homeostasis. To study the toxic response of Cr(VI) in living beings, four months
      old Wistar Strain rats were used in laboratory. The selected rats were divided
      into 5 categories and administered with pre-determined dose of Cr(VI) as well as
      antioxidants, viz. GSH, Se and alpha-tocopherol respectively. All the reagents
      and chemicals used in this study were either of analytical grade or highest
      purity. Protection offered by three non-enzymatic antioxidants against lipid
      peroxidation (LP) and oxidative stress in liver and kidney of Cr(VI) exposed rats
      has been studied. Increased malondialdehyde (MDA) and a significant depletion in
      GSH (Glutathione) status were observed in liver and kidney of Cr(VI) fed rats.
      However, administration with antioxidants inhibited lipid peroxidation (LP) as
      well as oxidative stress and restored GSH cycle in liver and kidney of Cr(VI)
      treated rats. Observations suggest that complexes formed by Cr(VI) in liver and
      kidney and the respective ligand preferences determined antioxidative influence
      of three non-enzymatic antioxidants, viz. glutathione (GSH), alpha-tocopherol and
      selenium (Se).

PMID- 24749209
TI  - Disposable baby diaper--a threat to the health and environment.
AB  - There is no doubt that disposable diapers are wonderfully convenient but are they
      safe for the babies? It is clear that there are also a number of potential
      dangers. Most of the parents are not aware of the adverse effects of this product
      being in contact with baby's reproductive organs 24 hours a day more than two
      years and the long-term effects it causes to the surroundings. Disposable diapers
      have been implicated by diapering proponents like leak proof polymers, super
      absorbent polymers and some scented chemicals which are the key factors for
      everything from chronic diaper rash, respiratory problems like asthma, male
      infertility even to testicular cancer. This article gives the detailed review of
      the health and other related problems in using the disposable baby diapers like
      cancer, liver damage, skin diseases, male infertility, birth abnormalities,
      respiratory problems, land fills, environmental pollution, toxic chemicals used
      etc.

PMID- 24749210
TI  - Annual review of health care management: revisiting the evolution of health
      systems organization.

PMID- 24749211
TI  - Health care organizations as complex systems: new perspectives on design and
      management.
AB  - PURPOSE: We discuss the impact of complexity science on the design and management
      of health care organizations over the past decade. We provide an overview of
      complexity science issues and their impact on thinking about health care systems,
      particularly with the rising importance of information systems. We also present a
      complexity science perspective on current issues in today's health care
      organizations and suggest ways that this perspective might help in approaching
      these issues. APPROACH: We review selected research, focusing on work in which we
      participated, to identify specific examples of applications of complexity
      science. We then take a look at information systems in health care organizations
      from a complexity viewpoint. FINDINGS: Complexity science is a fundamentally
      different way of understanding nature and has influenced the thinking of scholars
      and practitioners as they have attempted to understand health care organizations.
      Many scholars study health care organizations as complex adaptive systems and
      through this perspective develop new management strategies. Most important,
      perhaps, is the understanding that attention to relationships and
      interdependencies is critical for developing effective management strategies.
      RESEARCH AND PRACTICE IMPLICATIONS: Increased understanding of complexity science
      can enhance the ability of researchers and practitioners to develop new ways of
      understanding and improving health care organizations. ORIGINALITY/VALUE: This
      analysis opens new vistas for scholars and practitioners attempting to understand
      health care organizations as complex adaptive systems. The analysis holds value
      for those already familiar with this approach as well as those who may not be as
      familiar.

PMID- 24749212
TI  - Commentary on "Health care organizations as complex systems: new perspectives on
      design and management" by Reuben R. McDaniel, Dean J. Driebe, and Holly Jordan
      Lanham.
AB  - In this commentary, I highlight a few of the assertions made by McDaniel et al.
      (2013) about the importance of complexity science guided management practices,
      and extend these ideas specifically to how we might think about reducing
      seemingly intractable problems in health care such as patient safety, patient
      falls, hospital acquired infection, and the rise of chronic illness and obesity.
      I suggest that such changes will require managers and providers to view health
      care organizations and patients as complex adaptive systems and include patients
      as full participants in co-producing their health care.

PMID- 24749213
TI  - Horizontal and vertical integration of physicians: a tale of two tails.
AB  - PURPOSE: Researchers recommend a reorganization of the medical profession into
      larger groups with a multispecialty mix. We analyze whether there is evidence for
      the superiority of these models and if this organizational transformation is
      underway. DESIGN/METHODOLOGY APPROACH: We summarize the evidence on scale and
      scope economies in physician group practice, and then review the trends in
      physician group size and specialty mix to conduct survivorship tests of the most
      efficient models. FINDINGS: The distribution of physician groups exhibits two
      interesting tails. In the lower tail, a large percentage of physicians continue
      to practice in small, physician-owned practices. In the upper tail, there is a
      small but rapidly growing percentage of large groups that have been organized
      primarily by non-physician owners. RESEARCH LIMITATIONS: While our analysis
      includes no original data, it does collate all known surveys of physician
      practice characteristics and group practice formation to provide a consistent
      picture of physician organization. RESEARCH IMPLICATIONS: Our review suggests
      that scale and scope economies in physician practice are limited. This may
      explain why most physicians have retained their small practices. PRACTICAL
      IMPLICATIONS: Larger, multispecialty groups have been primarily organized by non
      physician owners in vertically integrated arrangements. There is little evidence
      supporting the efficiencies of such models and some concern they may pose
      anticompetitive threats. ORIGINALITY/VALUE: This is the first comprehensive
      review of the scale and scope economies of physician practice in nearly two
      decades. The research results do not appear to have changed much; nor has much
      changed in physician practice organization.

PMID- 24749214
TI  - Commentary on "Horizontal and vertical integration of physicians: a tale of two
      tails" by Lawton Robert Burns, Jeff C. Goldsmith, and Aditi Sen.

PMID- 24749215
TI  - The evolution of integrated health care strategies.
AB  - PURPOSE: To examine the evolution of health care integration strategies and
      associated conceptualization and practice through a review and synthesis of over
      25 years of international academic research and literature. METHODS: A search of
      the health sciences literature was conducted using PubMed and EMBASE. A total of
      114 articles were identified for inclusion and thematically analyzed using a
      strategy content model for systems-level integration. FINDINGS: Six major, inter
      related shifts in integration strategies were identified: (1) from a focus on
      horizontal integration to an emphasis on vertical integration; (2) from acute
      care and institution-centered models of integration to a broader focus on
      community-based health and social services; (3) from economic arguments for
      integration to an emphasis on improving quality of care and creating value; (4)
      from evaluations of integration using an organizational perspective to an
      emerging interest in patient-centered measures; (5) from a focus on modifying
      organizational and environmental structures to an emphasis on changing ways of
      working and influencing underlying cultural attitudes and norms; and (6) from
      integration for all patients within defined regions to a strategic focus on
      integrating care for specific populations. We propose that underlying many of
      these shifts is a growing recognition of the value of understanding health care
      delivery and integration as processes situated in Complex-Adaptive Systems (CAS).
      ORIGINALITY/VALUE: This review builds a descriptive framework against which to
      assess, compare, and track integration strategies over time.

PMID- 24749216
TI  - Hospital-physician relationships: implications from the professional service
      firms literature.
AB  - PURPOSE: The hospital-physician relationship (HPR) has been the focus of many
      scholars given the potential impact of this relationship on hospitals' ability to
      achieve socially and organizationally desirable health care outcomes. Hospitals
      are dominated by professionals and share many commonalities with professional
      service firms (PSFs). In this chapter, we explore an alternative HPR based on the
      governance models prevalent in PSFs. DESIGN/METHODOLOGY APPROACH: We summarize
      the issues presented by current HPRs and discuss the governance models dominant
      in PSFs. FINDINGS: We identify the non-equity partnership model as a governance
      archetype for hospitals; this model accounts for both the professional dominance
      in health care decisions and the increasing demand for higher accountability and
      efficiency. RESEARCH LIMITATIONS: There should be careful consideration of
      existing regulations such as the Stark law and the antikickback statue before the
      proposed governance model and the compensation structure for physician partners
      is adopted. RESEARCH IMPLICATIONS: While our governance archetype is based on a
      review of the literature on HPRs and PSFs, further research is needed to test our
      model. PRACTICAL IMPLICATIONS: Given the dominance of not-for-profit (NFP)
      ownership in the hospital industry, we believe the non-equity partnership model
      can help align physician incentives with those of the hospital, and strengthen
      HPRs to meet the demands of the changing health care environment.
      ORIGINALITY/VALUE: This is the first chapter to explore an alternative hospital
      physician integration strategy by examining the governance models in PSFs, which
      similar to hospitals have a high reliance on a predominantly professional staff.

PMID- 24749217
TI  - Engaging employed physicians: reconceptualizing the role of collective
      identification.
AB  - PURPOSE: This chapter proposes a paradigm shift in considering the collective
      identification of employed physicians and how it influences physician engagement.
      DESIGN/METHODOLOGY/APPROACH: There are many challenges for organizations
      employing physicians, particularly in terms of engagement in organizational
      initiatives. Prior research suggests this conflict stems from how physicians
      think of themselves as professionals versus employees (as forms of collective
      identification). Unfortunately, research is limited in addressing these dynamics.
      FINDINGS: This conceptual chapter considers the complex network of relationships
      that physicians perceive between the collectives to which they belong. A primary
      collective identification (i.e., the profession) is proposed to influence
      subsequent collective identification (i.e., the organization), and that these
      meanings and relationships along with contextual factors drive engagement.
      ORIGINALITY/VALUE: Health care organizations increasingly rely on engagement from
      their physicians to improve upon coordinated care. This proposed
      conceptualization offers new insight into the dynamics surrounding how and why
      employed physicians become engaged.

PMID- 24749218
TI  - Concluding remarks.

PMID- 24749219
TI  - Good night, sleep tight, don't let the bed bugs bite.

PMID- 24749220
TI  - Current status of mosquito control programs in North Carolina: the need for cost
      effectiveness analysis.
AB  - Mosquito control in the U.S. is both technically specialized and labor intensive
      with mosquito control programs (MCPs) carrying out services at federal, state,
      and local levels. The scope of each MCP varies depending on the needs of the
      region. In the 1970s, the North Carolina Department of Environment and Natural
      Resources formed the Public Health Pest Management (PHPM) section to play an
      active leadership role in training and support for local mosquito control
      programs across the state. PHPM was disbanded, however, in July 2011 due to state
      budget cuts. The extent to which recent budget shortfalls have impacted services
      provided by MCPs is largely unknown. Consequently, the primary objectives of the
      study described in this article were to 1) assess the current status of MCPs in
      North Carolina, 2) evaluate the extent to which the operational status of local
      MCPs affects public health, and 3) evaluate the impacts of losing the PHPM
      section in North Carolina.

PMID- 24749221
TI  - An outbreak of bed bug infestation in an office building.
AB  - Since 2000, resurgence in bed bugs has occurred in the U.S. Reports of
      infestations of homes, hospitals, hotels, and offices have been described. On
      September 1, 2011, complaints of itching and bites among workers in an office
      were reported to the Tennessee Department of Health. A retrospective cohort study
      and environmental assessments were performed in response to the complaints.
      Canines certified to detect live bed bugs were used to inspect the office and
      arthropod samples were collected. Of 76 office workers, 61 (80%) were
      interviewed; 39 (64%) met the case definition. Pruritic maculopapular lesions
      were consistent with arthropod bites. One collected arthropod sample was
      identified as a bed bug by three entomologists. Exposures associated with
      symptoms included working in a cubicle in which a canine identified bed bugs
      (risk ratio [RR]: 1.8; 95% confidence interval [CI]: 1.3-3.6), and self-reported
      seasonal allergies (RR: 1.6, 95% CI: 1.0-2.4). Bed bugs represent a reemerging
      and challenging environmental problem with clinical, psychological, and financial
      impacts.

PMID- 24749222
TI  - Outbreak of norovirus illness in a college summer camp: impact of cleaning on
      occurrence of norovirus on fomites.
AB  - During the summer of 2005 an outbreak of norovirus acute gastroenteritis occurred
      in a residential college summer camp and was reported to the local health
      department. The outbreak spread rapidly to several other groups concurrently
      sharing the same facilities. During the investigation, fomites were sampled at
      different times in dorm rooms and tested for norovirus. The number of norovirus
      positive rooms increased after the first room cleaning, from 40% to 73%. After
      the initial cleaning, the staff was instructed on proper cleaning and
      disinfection procedures and provided with disposable disinfecting wipes to reduce
      cross contamination, and the number of norovirus-positive rooms decreased to 30%.
      These findings reinforce the need for appropriate cleaning and disinfection
      procedures during a norovirus outbreak.

PMID- 24749223
TI  - 2012 NEHA/UL sabbatical report: vulnerability to potential impacts of climate
      change: adaptation and risk communication strategies for environmental health
      practitioners in the United Kingdom.
AB  - Climate change risk assessment, adaptation, and mitigation planning have become
      increasingly important to environmental health practitioners (EHPs). The NEHA/UL
      Sabbatical Exchange Award allowed me to investigate how EHPs in the UK are
      incorporating climate change planning and communication strategies into their
      work. Projected climate change risks in the UK include flooding, extreme heat,
      water shortages, severe weather, decreased air quality, and changes in vectors.
      Despite public perception and funding challenges, all the local government
      representatives with whom I met incorporated climate change risk assessment,
      adaptation, and mitigation planning into their work. The mandated Community Risk
      Register serves as a key planning document developed by each local government
      authority and is a meaningful way to look at potential climate change health
      risks. Adaptation and sustainability were common threads in my meetings. These
      often took the form of "going green" with transportation, energy efficiency,
      conserving resources, and building design because the efforts made sense
      monetarily as future cost savings. Communication strategies targeted a variety of
      audiences (EHPs, non-EHP government employees, politicians, and the general
      public) using a broad range of communication channels (professional training,
      lobbying, conferences and fairs, publications, print materials, Internet
      resources, social media, billboards, etc).

PMID- 24749224
TI  - Implementing systematic review in toxicological profiles: ATSDR and NIEHS/NTP
      collaboration.

PMID- 24749225
TI  - Mobile food trucks: California EHS-Net study on risk factors and inspection
      challenges.

PMID- 24749226
TI  - Fifty-five jobs of the future: part one.

PMID- 24749227
TI  - Yelp partners with health departments to improve food safety.

PMID- 24749228
TI  - The new frontier in personnel.

PMID- 24749229
TI  - Tag, catch, and other unnatural acts at recess (Circa 2014).
AB  - This commentary details a news event in which Carrie Weber Middle School in Port
      Washington, NY, supposedly banned students from using balls, playing tag, and
      doing cartwheels during recess. Public reaction in the form of news items,
      tweets, blogs, and commentary is sampled, and news releases from the Weber Middle
      School that were barely covered by the media and explain their decision to ban
      hardballs from 20-min recess are brought to light. The commentary then goes on to
      argue that such trending news events can be interpreted in terms of complex
      cultural histories, including in the case of Weber Middle School, much
      intellectual thought pioneered by human movement scholarship. Ideas about social
      nostalgia and memory, play, hegemony, invention of tradition, and cultural
      context are overviewed in light of their use in human movement studies and in
      interpreting the Weber Middle School issue. It is argued that current issues and
      initiatives surrounding obesity and sport for peace and development are, like the
      trending Weber Middle School news, sometimes not mapped or critiqued (terms
      coined by Markula-Denison and Silk in 2011) in the profound ways that cultural
      studies urge. The commentary ends in a call to scholars and practitioners of
      human movement studies for self-reflexivity and purposeful awareness of changing
      social definitions of the "unnatural."

PMID- 24749230
TI  - The role of students and content in teacher effectiveness.
AB  - The process of effective teaching--teaching that directly leads to student
      learning of standards-based content--is tenuous at best and easily disrupted by
      contextual and behavioral factors. In this commentary, I discuss the role of
      student support and mediation in teacher effectiveness and curricular reform. The
      most vocal students in physical education classes appear to thrive in the current
      multiactivity, recreation-oriented sport culture that dominates many U.S.
      physical education programs. They expect lessons with minimal skill and tactical
      instruction and with maximum opportunities to play ball. I also comment on Ward's
      emphasis on the value of content-rich definitions of teaching effectiveness and
      argue for additional disciplinary-based, concept-rich cognitive outcomes for
      physical education to complement and enrich skill, sport, and physical activity
      performance. I lend my voice to Rink's call for comprehensive measures of teacher
      accountability as the most critical next step in physical education reform. I
      conclude by contesting McKenzie and Lounsbery's accusation of "muddled goals" in
      physical education. Although physical education advocates may present diverse
      content perspectives, student learning is the primary goal of physical education.

PMID- 24749231
TI  - Teacher effectiveness research in physical education: the future isn't what it
      used to be.
AB  - This commentary was written in response to the Rink (2013), McKenzie and
      Lounsbery (2013), and Ward (2013) articles published earlier on teacher
      effectiveness in physical education (PE). The historical analyses of teacher
      effectiveness research in PE (TER-PE) presented in those 3 articles are briefly
      described, particularly as they represent a collective agenda in the first 3
      decades in this line of inquiry. That collective agenda was primarily driven by
      physical education researchers and P-12 teachers, who developed and explored
      empirically based best practices for effective teaching and learning in physical
      education, which informed much of the content knowledge and pedagogical content
      knowledge learned in physical education teacher education programs. Based on 2
      recent policy developments in many states, external threats to the previous
      agenda for TER-PE are presented by the author, who concedes that the lead for the
      future agenda for TER-PE will soon be taken out of the hands of researchers,
      teachers, and teacher educators and transferred to educational agencies in the
      form of new policies on initial teacher certification and the evaluation of in
      service teachers in a growing number of states.

PMID- 24749232
TI  - Effective teaching in physical education: using transportation metaphors to
      assess our status and drive our future.
AB  - In our reflection on Rink's (2013), McKenzie and Lounsbery's (2013), and Ward's
      (2013) characterizations of effective teaching in physical education (PE), 2
      themes emerged that permeate these diverse perspectives: policy and
      accountability. In our commentary, we focus our initial discussion on the
      implications that policy and accountability have on effective teaching in PE. A
      thread running through this discussion is the feasibility of promoting effective
      teaching in the context of current policy and demands for accountability. We
      provide an argument that school PE is in peril and draw parallels to previous
      commentaries of research on teaching. We conclude with comments highlighting
      steps that have the potential to revitalize school PE as a core element in school
      curricula. We argue that if school PE is to survive, it is critical that we
      advocate for policies that promote and support quality daily PE. To do that, we
      must convince decision makers that PE makes a valuable contribution to the school
      curriculum using data-based evidence. We must also recruit quality students into
      PE teacher education programs who are dynamic leaders in schools and communities.
      Finally, researchers in effective teaching in PE must make meaningful
      contributions to the broader field and work with interdisciplinary research teams
      to address issues related to promoting physical activity through education.

PMID- 24749233
TI  - Time to demonstrate how we impact student learning.
AB  - With the recent emphasis on evaluating teachers' effectiveness by the performance
      of their students, it should be no surprise that this subject has reached the
      physical education (PE) sector. This commentary examines 3 articles by Rink
      (2013), McKenzie and Lounsbery (2013), and Ward (2013), who each take a different
      perspective on measuring physical educators' effectiveness. The commentary,
      written from the standpoint of a public school district PE administrator,
      compares and contrasts the viewpoints and possible outcomes of each approach. The
      commentary seems to agree most with Rink. That is to say that there will be
      challenges in evaluating PE teachers based on student outcomes, but it is a
      reasonable expectation. These challenges include class size and determination of
      what outcomes we choose to use. These outcomes should be decided by physical
      educators, and the time is now. The commentary also points out the benefits of
      the other 2 approaches such as incorporating evaluation and assessment in teacher
      training programs at universities and inculcating a culture of "do as I do" not
      just "do as I say." In reaching the conclusion, it cannot be overstated that
      using student outcomes should be a measure of a teacher's effectiveness, but not
      the only measure. Classroom observations and management, levels of student
      physical activity, and student engagement continue to be critical components of
      teacher evaluation.

PMID- 24749234
TI  - Effective teaching in physical education: the view from a variety of trenches.
AB  - Determining the effectiveness of physical education teachers is a difficult
      process complicated by the expectations of the building principals, the
      extensiveness of national and state standards, student ability levels, and the
      severely limited time that the programs are allotted. The dearth of effective,
      efficient evaluation tools lends itself to program marginalization and continued
      erosion of time. Increasing research on the benefits of daily physical activity
      coupled with new "National Standards in Physical Education" may help to improve
      programs and teacher effectiveness. This commentary includes examples of the
      problems associated with determining teacher effectiveness and student
      achievement.

PMID- 24749235
TI  - Top 10 research questions related to body composition.
AB  - An understanding of body composition is crucial to understanding human health,
      disease, and function. Research in body composition has focused on the
      development of assessment methods, description of normal changes in body
      composition with growth and development and aging, and the changes that occur in
      body composition in response to challenges ranging from illness to planned
      interventions. Each focus is significant, and in a sense, they are
      interdependent, because technological advances allow more sophisticated questions
      to be addressed, which in turn drives the development of better methods.
      Significant advances have been made in each area, although perhaps surprisingly
      basic questions remain. For example, growth trajectories are often estimated from
      cross-sectional data, given the resources needed for long-term observational
      studies, and thus, longitudinal descriptive data are still needed. Along with
      advances in laboratory methods, development of field methods remains relevant for
      screening and clinical practice. Despite recognition of wide interindividual
      differences in intervention response, average outcomes continue to be emphasized.
      With technological advances, it is now possible to examine genetic along with
      nongenetic factors that underlie changes in body composition, and these
      techniques need to be applied in long-term, well-controlled trials. In this
      article, we review 10 key questions in related areas in which research is needed
      to continue to advance the field.

PMID- 24749236
TI  - Top 10 research questions related to energy balance.
AB  - Obesity is the result of a mismatch between the amount of calories consumed and
      the amount of calories expended during an extended period of time. This
      relationship is described by the energy balance equation, which states the rate
      of change in energy storage depots in the body are equal to the rate of energy
      intake minus the rate of energy expenditure. Although this relationship may
      appear easy to understand based on simple mathematics, in reality, a variety of
      known and unknown systems influence the components of energy balance (energy
      storage, energy intake, energy expenditure). Clearly, if a complete understanding
      of energy balance was apparent, worldwide levels of obesity would not have
      reached pandemic proportions due to effective prevention and treatment
      strategies. The aim of the present article is to provide a brief overview of the
      components of energy balance and to identify 10 key topics and unanswered
      questions that would move the research field forward if addressed. These topics
      are intentionally diverse and range from general themes (e.g., methodological
      issues) to specific areas (e.g., intensity of exercise required to alter energy
      intake). Although this list is not meant to be exhaustive, it does provide a
      research agenda for scientists involved in the study of energy balance and
      recommendations for public health professionals developing obesity interventions.

PMID- 24749237
TI  - Measurement agreement between estimates of aerobic fitness in youth: the impact
      of body mass index.
AB  - PURPOSE: The purpose of this study was to examine the impact of body mass index
      (BMI) on the agreement between aerobic capacity estimates from different
      Progressive Aerobic Cardiorespiratory Endurance Run (PACER) equations and the
      Mile Run Test. METHOD: The agreement between 2 different tests of aerobic
      capacity was examined on a large data set from 2 suburban school districts (n =
      1,686 youth in Grades 3-10). Difference estimates between the Mile Run Test and
      several PACER equations were computed, and residuals were examined using cluster
      analysis. The implication of the discrepancy between these tests was also
      examined using FITNESSGRAM health-related standards for BMI. Comparisons were
      made against corresponding estimates of peak oxygen consumption from the Mile run
      because this equation is more established. RESULTS: Results supported a 2-cluster
      solution. The discrepancy between tests was higher in participants with higher
      BMI scores (Z scores for residuals in this group ranged from -0.07 to 1.57). BMI
      was able to explain 30% to 34% of the disagreement between the Mile and different
      PACER equations of aerobic fitness. Classification analyses revealed that kappa
      scores were lower among PACER equations that do not include a BMI term (kappa =
      .12-.34 vs. .59-.81). Overall, the test-equating approach used in the Fitnessgram
      program to process PACER data had better agreement than alternative PACER
      equations that included BMI. CONCLUSION: The results support the inclusion of BMI
      in prediction equations used to estimate aerobic capacity from the PACER.

PMID- 24749238
TI  - One physical educator's career cycle: strong start, great run, approaching
      finish.
AB  - PURPOSE: This article is nested within a longitudinal project examining 6
      teachers' journeys along their career cycles (Lynn & Woods, 2010; Woods & Earls,
      1995; Woods & Lynn, 2001). Two participants from the initial 6 continue to teach
      K-12 physical education; 1 of these participants, Everett, is examined in the
      current study. This veteran teacher's career-cycle movement and the environmental
      factors that both enhanced and constrained his career development are examined
      through the lens of Fessler and Christensen's career cycle model (1992). METHOD:
      Data sources included: 8 formal interviews with Everett; formal interviews with
      his university teacher educators, student-teacher supervisor, principal, and
      spouse; informal interviews; field notes; and systematic teaching observations.
      An interpretative framework was used to assess the perceptions and meanings
      Everett gave to experiences as a physical educator and coach. RESULTS: Several
      factors acutely influenced Everett's career progression, including: (a) his
      individual disposition, (b) the impact and continued influence of a professional
      preparation program, and (c) his school and community support. He entered the
      profession with great promise and spent most of his career in the enthusiastic
      and growing, and the career stability, stages before shifting into the career
      frustration stage where he currently remains. CONCLUSIONS: Everett was able to
      negotiate personal and organizational environmental factors that have been
      identified as barriers for some physical educators. Therefore, viewing his
      professional life through the lens of the career cycle provides insights into the
      areas of change necessary to motivate and retain high-quality physical educators
      such as Everett.

PMID- 24749239
TI  - Validation of an instrument to measure high school students' attitudes toward
      fitness testing.
AB  - PURPOSE: The purpose of this investigation was to develop an instrument that has
      scores that are valid and reliable for measuring students' attitudes toward
      fitness testing. METHOD: The method involved the following steps: (a) an
      elicitation study, (b) item development, (c) a pilot study, and (d) a validation
      study. The pilot study included 427 student-completed instruments from 3 schools.
      Pilot study data analyses were conducted resulting in a proposed model for the
      final study. Participants for the final study were 1,199 students (524 boys and
      675 girls) from 13 schools. Thirty-six experts in physical education pedagogy
      were the participants of the content validity study. RESULTS: The data fit a
      model with 4 factors: cognitive, affective-enjoyment, affective-feelings, and
      affective-teacher. Fit statistics from the confirmatory factor analysis indicated
      an overall good fit of the data to this model. Goodness of Fit Index (GFI), GFI
      Adjusted for Degree of Freedom, root mean square error of approximation,
      Bentler's Comparative Fit Index, and Bentler & Bonett's Normed Fit Index scores
      were .892, .862, .080, .920, and .910, respectively. The Guttman-Cronbach alpha
      reliability coefficients for the 4 factors and overall model were: cognitive
      (alpha = .919), affective-enjoyment (alpha = .887), affective-feelings (alpha =
      .865), affective-teacher (alpha = .801), and overall (alpha = .902). CONCLUSION:
      Scores from this instrument indicate that we can measure students' attitudes
      toward fitness testing well and can therefore permit further examination into the
      role these attitudes play in future physical activity.

PMID- 24749240
TI  - Effects of a simulated tennis match on lymphocyte subset measurements.
AB  - Tennis is an activity requiring both endurance and anaerobic components, which
      could have immunosuppressive effects postexercise. PURPOSE: The purpose of this
      investigation was to determine the effect of a simulated tennis match on
      apoptotic and migratory markers on lymphocyte subsets. METHOD: Male high school
      (n = 5) and college (n = 3) tennis players (M(age) = 18.9 +/- 3.3 years)
      completed 10 sets of a tennis protocol including serves, forehand strokes, and
      backhand groundstrokes with 1-min rest periods between sets. Apoptosis antigen 1
      receptor (CD95) and chemokine receptor fractalkine (CX3CR1) expression was
      analyzed on helper T lymphocytes (CD4+), cytotoxic T lymphocytes (CD8+), and B
      lymphocytes (CD19+) twice, at resting baseline and immediately after all 10 sets
      of the tennis protocol. RESULTS: An increase was observed in each lymphocyte
      subtype (p < .02, effect size = .41), and comparison of absolute changes revealed
      increases in CD4+/CD95+, CD8+/CD95+, and CD8+/CX3CR1 lymphocytes following the
      tennis protocol (p < .01, effect size = .43), but not in CD19+ cells.
      CONCLUSIONS: A simulated tennis match has adequate intensity to induce immune
      modulations in terms of increased cell death and cellular migration in T
      lymphocyte subsets. Lymphocytopenia following tennis play is influenced by both
      apoptotic and migratory mechanisms.

PMID- 24749241
TI  - Increasing functional variability in the preparatory phase of the takeoff
      improves elite springboard diving performance.
AB  - PURPOSE: Previous research demonstrating that specific performance outcome goals
      can be achieved in different ways is functionally significant for springboard
      divers whose performance environment can vary extensively. This body of work
      raises questions about the traditional approach of balking (terminating the
      takeoff) by elite divers aiming to perform only identical, invariant movement
      patterns during practice. METHOD: A 12-week training program (2 times per day;
      6.5 hr per day) was implemented with 4 elite female springboard divers to
      encourage them to adapt movement patterns under variable takeoff conditions and
      complete intended dives, rather than balk. RESULTS: Intraindividual analyses
      revealed small increases in variability in the board-work component of each
      diver's pretraining and posttraining program reverse-dive takeoffs. No
      topological differences were observed between movement patterns of dives
      completed pretraining and posttraining. Differences were noted in the amount of
      movement variability under different training conditions (evidenced by higher
      normalized root mean square error indexes posttraining). An increase in the
      number of completed dives (from 78.91%-86.84% to 95.59%-99.29%) and a decrease in
      the frequency of balked takeoffs (from 13.16%-19.41% to 0.63%-4.41%) showed that
      the elite athletes were able to adapt their behaviors during the training
      program. These findings coincided with greater consistency in the divers'
      performance during practice as scored by qualified judges. CONCLUSION: Results
      suggested that on completion of training, athletes were capable of successfully
      adapting their movement patterns under more varied takeoff conditions to achieve
      greater consistency and stability of performance outcomes.

PMID- 24749242
TI  - Changes in kicking pattern: effect of experience, speed, accuracy, and effective
      striking mass.
AB  - PURPOSE: The purposes of this study were to: (a) examine the effect of experience
      and goal constraints (speed, accuracy) on kicking patterns; (b) determine if
      effective striking mass was independent of ankle velocity at impact; and (c)
      determine the accuracy of kicks relative to independent factors. METHOD: Twenty
      participants were recruited to kick at 3 different velocities with and without an
      accuracy requirement. Multivariate analysis of variance determined if relative
      timing of joint angular velocities changed during the kick. Chi-square analysis
      determined if calculated effective mass was independent of ankle velocity at
      impact. Analysis of variance (ANOVA) was used to examine differences in absolute
      constant error and variable error according to independent factors. RESULTS:
      Results indicated that experience and speed affect absolute timing of joint
      velocities with no changes in the relative timing of peak joint velocity across
      independent factors. Chi-square analysis indicated that calculated effective mass
      is not independent of ankle velocity. ANOVA indicated that experienced performers
      displayed less variability error than did inexperienced performers. CONCLUSION:
      It was concluded that: (a) Experience, velocity, and accuracy do not affect the
      relative timing of kicks; (b) kickers trade ankle velocity at impact for greater
      effective striking mass and ball velocity; and (c) variability in ball placement
      is affected by experience.

PMID- 24749243
TI  - Kinematics of self-initiated and reactive karate punches.
AB  - PURPOSE: This study investigated whether within-task expertise affects the
      reported asymmetry in execution time exhibited in reactive and self-initiated
      movements. METHOD: Karate practitioners and no-karate practitioners were compared
      performing a reverse punch in reaction to an external stimulus or following the
      intention to produce a response (self-initiated). The task was completed
      following the presentation of a specific (i.e., life-size image of opponent) or
      general stimulus and in the presence of click trains or white noise. RESULTS:
      Kinematic analyses indicated reactive movement had shorter time to peak velocity
      and movement time, as well as greater accuracy than self-initiated movement.
      These differences were independent of participant skill level although peak
      velocity was higher in the karate practice group than in the no-karate practice
      group. Reaction time (RT) of skilled participants was facilitated by a specific
      stimulus. There was no effect on RT or kinematic variables of the different type
      of auditory cues. CONCLUSIONS: The results of this study indicate that asymmetry
      in execution time of reactive and self-initiated movement holds irrespective of
      within-task expertise and stimulus specificity. This could have implications for
      training of sports and/or relearning of tasks that require rapid and accurate
      movements to intercept/contact a target.

PMID- 24749244
TI  - [Computer search for molecular mechanisms of ulcerogenic action of nonsteroidal
      antiinflammatory drugs].
AB  - "Peptic ulcers" is the most frequent side effect of non-steroidal anti
      inflammatory drugs (NSAIDs). Experimental data indicate that pathogenesis of
      peptic ulcers cannot be explained only by the inhibition of cyclooxygenases. The
      knowledge about other molecular mechanisms of action of drugs related with
      development of peptic ulcers could be useful for design of new safe NSAIDs.
      However, considerable time and material resources are needed for corresponding
      experimental research. For simplification of experimental search, we have
      developed an approach for in silico identification of probable molecular
      mechanisms of action of drugs related with its side effects. We have created the
      set of NSAIDs containing 85 substances with data about structures and side
      effects. The computer program PASS (Prediction of Activity Spectra for
      Substances) predicting more than 3000 molecular mechanisms of action based on
      structural formula of substances was used to estimate unknown molecular
      mechanisms of action for these set of NSAIDs. Statistically significant
      relationships between predicted molecular mechanisms of action and development of
      peptic ulcers have been established. We have discovered twenty-six molecular
      mechanisms of action (two known previously and twenty-four new) which probably
      related with development of peptic ulcers. By analyzing of Gene Ontology data,
      signal and metabolic pathways, publications in Medline, we formulated hypotheses
      about the role of ten molecular mechanisms of action in pathogenesis of peptic
      ulcer.

PMID- 24749245
TI  - [Protein-protein interactions of cytochromes P450 3A4 and 3A5 with their
      intermediate redox partners cytochromes b5].
AB  - Molecular interactions between proteins redox partners (cytochromes P450 3A4, 3A5
      and cytochrome b5) within the monooxygenase system, which is known to be involved
      in drug biotransformation, were investigated. Human cytochromes P450 3A4 and 3A5
      (CYP3A4 and CYP3A5) form complexes with various cytochromes b5: the microsomal
      (b5mc) and mitochondrial (b5om) forms of this protein, as well as with 2
      "chimeric" proteins, b5(om-mc), b5(mc-om). Kinetic constants and equilibrium
      dissociation constants were determined by the SPR biosensor. Essential
      distinction between CYP3A4 and CYP3A5 was only observed upon their interactions
      with cytochrome b5om. Electroanalytical characteristics of electrodes with
      immobilized hemoproteins were obtained. The electrochemical analysis of CYP3A4,
      CYP3A5, b5mc, b5om, b5(om-mc), and b5(mc-om) immobilized on screen printed
      graphite electrodes modified with membranous matrix revealed that these proteins
      have very close reduction potentials -0.435 - -0.350 V (vs. Ag/AgCl). Cytochrome
      b5mc was shown to be capable of stimulating the electrocatalytic activity of
      CYP3A4 to testosterone.

PMID- 24749246
TI  - [Irreversible chemical AFM-fishing for the detection of low-copied proteins].
AB  - The atomic-force microscopy-based method of irreversible chemical AFM-fishing
      (AFM-IF(Ch)) has been developed for the detection of proteins at ultra-low
      concentrations in solution. Using this method, a very low concentration of
      horseradish peroxidase (HRP) protein (10(-17) M) was detected in solution. A
      theoretical model that allows the description of obtained experimental data, is
      proposed. This model takes into consideration both the transport of the protein
      from the bulk solution onto the AFM-chip surface and its irreversible binding to
      the activated area.

PMID- 24749247
TI  - [Preparation of monospecific antibodies against isoform 2 of translation
      elongation factor 1A (eEF1A2)].
AB  - Amino acid sequences of eukaryotic translation elongation factor isoform 1
      (eEF1A1) and 2 (eEF1A2) were compared and two peptide fragments of eEF1A2 were
      chosen as linear antigenic determinants for generation of monospecific
      antipeptide antibodies. Selected peptides were synthesized, conjugated to bovine
      serum albumin (BSA) and used for mice immunizations. Antibodies, produced against
      the eEF1A2 fragment 330-343 conjugated to BSA, specifically recognized this
      isoform in the native and partially denatured states but did not interact with
      the eEF1A1 isoform. It was shown that these monospecific anti-eEF1A2 antibodies
      could be employed for eEF1A2 detection both by enzyme-linked immunosorbent assay
      and by immunoblotting.

PMID- 24749248
TI  - [Cytoplasmic superoxide dismutase activity is a sensitive indicator of the
      antioxidant status of the rat liver and brain].
AB  - Several parameters of the cytoplasmic enzymatic antioxidant system of the liver
      and brain of the rat have been investigated under conditions of immobilization
      stress and of an antioxidant preparation in the diet of animals. These included
      superoxide dismutase (SOD) and glutathione reductase (GR) activities and
      nonspecific NADPH oxidation. Only changes in the activity of SOD both in the
      liver and brain were revealed. In the liver of animals that receive no
      preparation, a decrease in the activity of SOD after 30-min immobilization and
      its restoration after a 360-min immobilization were observed. In the brain, the
      activity of SOD decreased only in preconditioned animals after 30 and 360 min of
      exposure to stress. In addition, the activity of SOD in the brain of
      preconditioned animals, both stressed and unstressed, was lower than in the
      corresponding groups of control animals. It is probable that, under the
      conditions of immobilization stress, the level of reactive oxygen species (ROS)
      and as a consequence the activity of SOD decrease. The intake of an antioxidant
      preparation under these conditions seems to be not correct.

PMID- 24749249
TI  - [Polymorphism of the plasminogen activator inhibitor type 1 gene, plasminogen
      level and thrombosis in patients with antiphospholipid syndrome].
AB  - The frequency of venous and arterial thromboses and plasminogen level were
      investigated in 78 patients with antiphospholipid syndrome (APS), 35 of whom with
      systemic lupus erythematosus (SLE+APS) and 43 - with primary APS (PAPS). The
      levels and genotype of plasminogen activator inhibitor type 1 (PAI-1) were
      determined in 45 patients with APS, of whom 21 patients with SLE + APS and 24
      patients with PAPS. A control group included 10 healthy individuals without
      autoimmune disease signs and thromboses on period of investigation and in past
      history. It was shown for the first time that for one third of 67 patients with
      APS and thromboses high positive levels of antiphospholipid antibodies (aPL) are
      associated with low plasminogen levels. The levels of PAI-1 antigen measured by
      ELIZA method, which detects active, latent and bound with plasminogen activator
      PAI-1, were opposed with frequency of thromboses in APS patients. Correlation
      between the high and increased levels of PAI-1 and high positive aPL levels was
      found for one third of 43 patients with APS and thrombosis. One of the possible
      mechanisms of this interconnection was considered. It was shown that arterial
      and, to a more extent, venous thromboses are associated with the 4G/5G
      polymorphism of PAI-1 gene and high plasma level of the inhibitor in 79% of APS
      patients. At the presence of the 4G allele patients with SLE+APS had higher PAI-1
      levels than patients with PAPS. The obtained results show that measuring the
      levels of plasminogen and PAI-1 as well as the 4G/5G polymorphism of PAI-1 gene
      which is associated with thromboses may have the practical significance for
      identification of high risk of thrombosis in APS patients.

PMID- 24749250
TI  - [Mean platelet volume: interactions with platelet aggregation activity and
      glycoprotein IIb-IIIa and Ib expression levels].
AB  - Increased mean platelet volume (MPV) is an independent risk factor of thrombotic
      events in patients with cardiovascular diseases. Interactions of MPV with
      platelet aggregation activity and contents of glycoprotein (GP) IIb-IIIa
      (alphaIIb/beta3 integrin, fibrinogen receptor) and GP Ib (von Willebrand factor
      receptor) were investigated in this study. Investigation was performed in a group
      of healthy volunteers (n = 38) and in a group of patients with acute coronary
      syndrome (ACS). In patients blood was collected at days 1, 3-5 and 8-12 after ACS
      development. As an antiaggregant therapy all patients received acetylsalicylic
      acid (ASA, inhibitor of thromboxane A2 synthesis) and most of them--clopidogrel
      (ADP receptor antagonist) with the exception of part of the patients (n = 44) at
      day 1 who had not taken clopidogrel before first blood collection. In volunteers
      platelet aggregation was stimulated by 1.25, 2.5, 5 and 20 M ADP, and in patients
      -by 5 and 20 M ADP. GP IIb-IIIa and GP Ib content on platelet surface was
      measured using 125I-labelled monoclonal antibodies. GP IIb-IIIa and GP Ib genetic
      polymorphisms were determined in ACS patients. In healthy donors significant
      correlations between MPV and aggregation levels were revealed at 1.25 and 2.5 M
      ADP (coefficients of correlation (r)--0.396 and 0.373, p < 0.05) and at 5 and 20
      those interactions did not reach significant level (r--0.279 and 0.205, p >
      0.05). Correlations between MPV and aggregation levels were observed at day 1 of
      ACS in a subgroup of patients who received ASA but had not started clopidogrel
      treatment (r--0.526, p < 0.01 and 0.368, p < 0.05 for 5 and 20 M ADP
      respectively). Interactions between these parameters were not registered upon
      combined treatment with ASA and clopidogrel. Strong direct correlations between
      MPV and GP IIb-IIIa and GP Ib contents were detected in healthy donors and ACS
      patients (at all time points) -r from 0.439 to 0.647 (p < or = 0.001 for all
      correlations). Genetic polymorphisms of GP IIb-IIIa (GP IIIa Leu33Pro) and GP Ib
      ((-5)T/C (Kozak) and Thr145Met) identified in ACS patients did not affect
      expression levels of corresponding glycoproteins. The data obtained indicated
      that increased MPV values correlate with increased platelet aggregation activity
      and enhanced GP IIb-IIIa and GP Ib expression.

PMID- 24749251
TI  - [Peculiarities of vanadium determinaion in whole blood by ICP-MS].
AB  - The parameters of vanadium determination by ICP-MS in whole blood are presented.
      Conditions for blood sample preparation to reduce measure errors and to determine
      vanadium at the reference concentration level were optimized. The accuracy of the
      results is confirmed by analysis of standard blood samples Seronorm L1, L2 and
      L3. Vanadium mean in whole blood for the group of children from the town of
      Chusovoy (n = 80) was 1.29 +/- 0.45 microg/L, and vanadium mean for grown-ups
      from the town of Chusovoy was 1.63 +/- 0.25 microg/L.

PMID- 24749252
TI  - [The effects of preparation "Histochrome" in biochemical parameters of blood for
      patients with cardiopathologies].
AB  - The effects of the small doses of the preparation Gistochrome, containing natural
      polyhydroxynaphtoquinoine echinochrom A from flat sea urchin Scaphechinus
      mirabilis, on blood biochemical parameters have been studied in patients with
      cardiovascular diseases. Gistochrome administration influenced the LPO
      antioxidant protection system, indicating reinforcement of antioxidant protection
      mechanisms. Gistochrome modulated the immune status and the plasma cytokine
      profile. Thus, Gistochrome may be recommended as means of additional therapy for
      patients with cardiovascular diseases for correcting the metabolic, immunological
      and redox impairments.

PMID- 24749253
TI  - [Advances of selenium supplementation in posttraumatic stress disorder risk group
      patients].
AB  - Posttraumatic stress disorder (PTSD) is a complex of symptoms developed in a
      patient after traumatic event. The basis of PTSD pathophysiology is hyper
      activation of neurones under stress factors influence, so-called excitotoxicity,
      followed by oxidative stress (OS) because of an accumulation of free radicals.
      Lipid peroxidation can lead to neurons damage. Neurons are especially susceptible
      to OS, changing signal transduction and information processing mechanisms.
      Clinically excitotoxicity preforms as different acute and/or chronic stress
      reactions and can cause PTSD. Selenium (Se) is involved on different stages of
      transport and metabolism of Glutamate. Research aim: to access PTSD incidence, OS
      parameters and their adjustment advances using organic Se in PTSD risk group
      patients. PTSD symptomatic severity (in PCL-M points) reduced for 5.85% to
      baseline, Prevalence Rate reduced for 46.03% to baseline in Se group patients. We
      can conclude that: 1) there is a statistically reliable correlations between the
      incidence of PTSD and OS parameters, between PTSD symptomatic severity and OS
      parameters; 2) the use of Se during the mission can reduce the OS parameters,
      minimize the incidence of PTSD and reduce the PTSD symptomatic severity.

PMID- 24749254
TI  - [Effect of anaesthesia on incidence of postoperative delirium after major
      abdominal surgery in elderly patients].
AB  - Delirium can be caused by haemodynamics abnormalities during anaesthesia. The
      main role in delirium appearance is given to decreasing of cerebral perfusion
      pressure. Especially it can happen in patients with underlying intracranial
      hypertension. Anaesthetics effects on intracranial pressure are different
      therefore cerebral hypoperfusion can happens in these patients even without
      systemic hypotension. Purpose of the study was to define an effect of cerebral
      perfusion pressure decreasing during different technics of anaesthesia on
      frequency of delirium in elderly patients after major abdominal surgery. The
      article deals with results of study of 182 patients (medium age 69 y.o.)
      underwent elective major abdominal surgery. Delirium frequency was 11%,
      continuing of delirium was 3 days. The frequency of delirium was higher in
      patients who had got anaesthesia based on sevoflurane. Additionally these
      patients had higher frequency of cerebral perfusion pressure decreasing.
      Conclusions; Anaesthesia based on sevoflurane is characterized by higher
      frequency of postoperative delirium in elderly patients after major abdominal
      surgery.

PMID- 24749255
TI  - [Correction of hemodynamics and heart rate disorders in paitients with right
      coronary artery disease].
AB  - PURPOSE OF THE STUDY: To analyze a correlation between sino-atrial node automatic
      activity and atrio-ventricular conductivity in patients with lower acute
      myocardial infarction (AMI) and atrio-ventricular blockade II-III (AVB) during
      infusion therapy. MATERIALS AND METHODS: Retrospective analysis of care for
      patients with AMI and AVB was carried out. Infusion therapy effects were studied
      in 12 patients with right coronary artery disease and AVB. RESULTS: Infusion
      therapy in patients with lower acute myocardial infarction, atrio-ventricular
      blockade and right ventricular failure corrects haemodynamic and dromotropic
      disturbances. Systolic arterial pressure (SAP) increased to 100,4 mmHg (9,9)
      after infusion of 400 mLin comparison with SAP after infusion of 200 mL (p =
      0.003), Diastolic arterial pressure (DAP) increased to 58,7 mmHg (6,8) in
      comparison with DAP after infusion of 200 mL (p = 0.011), central venous pressure
      (CVP) decreased to 12.2 cmH2O (3,7) in comparison with CVP after infusion of 200
      mL (p = 0.003). Mode of AVB degree indicator changed t 0O (0;0) (p = 0.028).
      CONCLUSIONS: Infusion volume therapy should be used for correction of right
      ventricular failure and disturbances of atrio-ventricular conductivity in case of
      right ventricular failure absence.

PMID- 24749256
TI  - [Association of cardiovascular system and endothelial dysfunction indicators in
      patients with hemorrhagic shock].
AB  - Endothelial dysfunction is a universal mechanism of pathogenesis of many critical
      conditions. Goal of the study was to assess a relation of cardiovascular system
      and endothelial dysfunction indicators in patients with hemorrhagic shock.
      MATERIALS AND METHODS: 17 patients with hemorrhagic shock 3 were involved in the
      study. All patients received infusion therapy, artificial lung ventilation after
      tracheal intubation and symptomatic treatment in prehospital period. Common
      volume of blood loose was 2900 +/- 200 mL. The patients received infusion,
      transfusion, inotrope, antibacterial, respiratory and symptomatic therapy in ICU
      after surgical treatment. Cardio-vascular system parameters were assessed by
      Tischenko method of integral reography. Number of red cells, hemoglobin, lactate,
      endotelin-1 and Wb-factor of venous blood were studied before surgery, in 12 and
      in 24 hours after. Morphological study of the omentumbiopsy was carried out.
      RESULTS: Performed correlation analysis showed statistically significant
      relations of cardiovascular system and endothelial dysfunction indicators in
      patients with hemorrhagic shock. Endothelial dysfunction occurs in patients with
      hemorrhagic shock 3. The endothelial dysfunction correlates with parameters of
      cardio-vascular system and tissue perfusion.

PMID- 24749257
TI  - [Prediction of mortality in patients with acute hepatic failure].
AB  - The article deals with a study of 243 patients (from 18 to 65 years old) with
      acute hepatic failure. Purpose of the study was to evaluate the predictive
      capability of severity scales APACHE III, SOFA, MODS, Child-Pugh and to identify
      mortality predictors in patients with acute hepatic failure. Results; The best
      predictive ability in patients with acute hepatic failure and multiple organ
      failure had APACHE III and SOFA scales. The strongest mortality predictors were:
      serum creatinine > 132 mmol/L, fibrinogen < 1.4 g/L, Na < 129 mmol/L.

PMID- 24749258
TI  - [Characteristics of perioperative period in Xenon-based combined general
      anaesthesia in neurosurgery].
AB  - Neuroprotection could be the aim to use Xenon for general anesthesia. However the
      experience of Xenon anesthesia in neurosurgery is quite limited. The appraisal of
      Xenon based anesthesia was accomplished in 12 patients during various brain
      surgery. Xe in concentration 65% was used to maintenance of anesthesia, other
      medication was avoided. As a resuIt there were 8 cases of arterial hypertension
      and 2 cases of superficial hypnotic state. Excitation (n = 3), hyperdynamic
      reaction (n = 8), PONV (n = 8) were detected in early postoperative period. An
      analysis of this study suggests a conclusion that studied method of Xenon-based
      anesthesia is inexpedient for neurosurgery.

PMID- 24749259
TI  - [Dexmedetomidine use for postoperative adrenergic analgesia and sedation in
      abdominal surgery].
AB  - Comparative study of postoperative analgesia and sedation with trimeperidine and
      dexmedetomidine and their effects on haemodynamics and vegetative nervous system
      was performed. Assessment of analgesia and sedation during vagotonia (first part
      of the study) and hypokinetic type of haemodynamics (second part of the study)
      was carried out with visual analogue scale (VAS) and Richmond scale. Results of
      the study showed that dexmedetomidine is more effective and safer than
      trimeperidine for analgesia and sedation in patients with spontaneous breathing
      after abdominal surgery. Dexmedetomidine use allows keeping optimal type of
      haemodynamics and vegetative nervous system parameters on first day of
      postoperative period.

PMID- 24749260
TI  - [Comparison of epidural and opioid analgesia effects on frequency of paralytic
      ileus development in patients of surgical intensive care unit].
AB  - The impact of epidural analgesia (EA) on bowel peristalsis in Surgical Intensive
      Care Unit (SICU) patients is not well known. This study was designed to determine
      if EA improves bowel motility and decreases the incidence of postoperative
      paralytic ileus compared to patients receiving systemic opioid analgesia (OA).
      Through prospective cohort study we investigated 386 SICU patients who received
      EA [n = 70 (18.13%)], or OA +/- ketorolac trometamol [n = 316 (81.87%)]. We
      showed that EA does not improve time to defecation and does not decrease the
      incidence of paralytic ileus in SICU patients.

PMID- 24749261
TI  - [Comparative assessment of prolonged femoral nerve blockade and epidural
      analgesia for postoperative pain in total knee joint arthroplasty].
AB  - The study deals with two mostly discussed techniques of postoperative analgesia
      for total knee joint arthroplasty. Surgeries were performed under subarachnoid
      anaesthesia with intravenous sedation. 9 patients of first group in received
      prolonged femoral nerve blockade as a component of multimodal analgesia. 8
      patients of second group received epidural infusion of naropine. If basic
      technique of analgesia was not effective patients received trimeperidine 20 mg
      intramuscular. Patients of second group had less pain syndrome (in order to
      visual analogue scale) and did not need additional administration of opioids.

PMID- 24749262
TI  - [Experience of extracorporeal membrane oxygenation in critical care of
      respiratory failure in newborn with congenital diaphragmatic hernia in perinatal
      center].
AB  - The article deals with an experience of veno-arterial extracorporeal membrane
      oxygenation use in preterm infants with congenital diaphragmatic hernia during
      postoperative period in the perinatal center.

PMID- 24749263
TI  - [Effect of early multimodal rehabilitation on postoperative recovery after
      abdominal hysterectomy].
AB  - Purpose of the study was to evaluate the impact of the use of enhanced recovery
      after surgery for the postoperative period, and the inflammatory response after
      hysterectomy. INTRODUCTION: Methods Prospectively, 50 patients ASA 1-2 aged 42-72
      years were randomized into two groups: the ERAS group (n = 25) and the control
      group (CG) with traditional perioperative management (n = 25). combined spinal
      and epidural anesthesia technique was used in all patients. Patient-controlled
      epidural analgesia in the ERAS group and multimodal analgesia with combination of
      paracetamol, tramadol and ketoprofen in the control group were used
      postoperatively. We measured plasma concentrations of interleukin-6 (IL-6),
      interleuki-nIL-1beta (IL-1beta) and C-reactive protein (CRP) preoperatively and
      at 24 hours and 7 days after surgery. Data were analyzed by Mann-Whitney U test
      and presented as median (25th- 75th percentiles). RESULTS: There was no
      statistically significant differences in the IL-6 and IL-1beta concentrations
      throughout the study. At 6 and 24 hours the pain severity of according to VAS was
      higher in the control group at rest and on coughing during all study stages. We
      found no correlation between the level of pain and plasma concentrations of IL
      1beta and IL-6. The plasma concentration of CRP in the control group was higher
      at 24 hours and at 7 days after surgery: (P < 0.01). Level of CRP in the control
      group tended to increase during the observation period. CONCLUSIONS: In our
      study, the serum concentration of IL-6 and IL-1beta did not depend on the method
      of postoperative pain management. Using the ERAS protocol reduced postoperative
      plasma concentration of CRP. The increased level of CRP in the control group may
      be related with autoimmune reaction in wound due to delayed mobilization of
      patients.

PMID- 24749264
TI  - [Role of intra-abdominal hypertension in the development and outcome of ovarian
      hyperstimulation syndrome].
AB  - OBJECTIVE: To evaluate the role of intraabdominal hypertension in the development
      and outcome of ovarian hyperstimulation syndrome. MATERIAL AND METHODS: 60
      patients with varying degrees of ovarian hyperstimulation syndrome (OHSS) due to
      ongoing pregnancy were involved in the study. Intraabdominal pressure (IAP) was
      measured in the bladder. Performance of abdominal perfusion pressure, filtration
      gradient, extensibility and compliance of the anterior abdominal wall were
      evaluated. A size of the ovaries, chorionic condition and ascites were determined
      by ultrasonic method. Relation of pregnancy outcome and IAP was analyzed.
      RESULTS: The mean value of IAP in patients with light form of ovarian
      hyperstimulation syndrome was 7.05 +/- 1.76 mm Hg, 13.65 +/- 1.92 mm Hg in
      patients with moderate form, and 20.60 +/- 2.52 mm Hg in patients with severe
      form of OHSS. The leading factors in the development and progression of
      intraabdominal hypertension (IAH) are the volume of the ovaries, ascites, and
      extensibility of the abdominal wall. The comparison of pregnancy outcome and
      severity of IAP revealed a strong positive correlation--r = 0.726, p < 0.001.
      CONCLUSION: Evaluation of the severity of intra-abdominal hypertension in
      patients with ovarian hyperstimulation syndrome with considering the clinical
      data and results of laboratory and instrumental studies allow clarifying the
      severity of condition and predict the potential complications and pregnancy
      outcomes.

PMID- 24749265
TI  - [Assessment of sugammadex use efficiency and safety for neuromuscular block
      reversion].
AB  - Blockade of neuromuscular conductivity is a considered one of basic part of a
      patient protection in a concept of a balanced multicomponent anesthesia. The
      controlled neuromuscular paralysis in a combination of a sedation, an analgesia
      and a hyporeflection not only provides comfortable conditions to surgeons for
      carrying out surgeries, but also allows to manage a gas exchange, blood
      circulation and a metabolism in a patient. However in clinical practice there is
      such complication after application of muscular relaxant (not depolarizing) as a
      residual curarization. The residual curarization is interfaced to deterioration
      of the respiratory answer to a hypoxemia, swallowing dysfunction that
      significantly increased risk of aspiration and risk of postoperative pulmonary
      complications. Until recent time acetylcholinesterase inhibitors or prolonged ALV
      before spontaneous regression of the neuromuscular block were applied in clinical
      practice for the purpose of restoration of adequate neuromuscular conductivity
      and elimination of a residual curarization. However there are number of the
      circumstances limiting application of preparations of this group including it is
      related with rather high frequency of side effects and lack of efficiency at the
      deep neuromuscular block. Today in an arsenal of the anesthesiologist there was
      the latest chemical - sugammadex. Sugammadex realizes a new approach to
      restoration of the neuromuscular conductivity.

PMID- 24749266
TI  - [Emergency fiberoptic bronchoscopy for diagnostics and treatment of lung
      atelectasis].
AB  - The article deals with results of fiberoptic bronchoscopy using during treating
      of patients suffering atelectasis. According to the research atelectasis is
      likely to advance in the first three days after serious patients have been
      admitted to the intensive therapy unit or after operative treatment. Left-sided
      atelectasis is half as widespread again the right-sided one. The research
      highlights the effectiveness of atelectasis X-ray diagnosis. Fiberoptic
      bronchoscopy in almost all the cases allowed diagnosing the degree of
      tracheobronchial tree obstruction and its causes. Single suction fiberoptic
      bronchoscopy leads to normalization and encouraged positive dynamics in 76% of
      all the cases (57 patients). Repeated endoscopic sanation in the first two days
      was necessary for 25 patients (25.3%) with unresolved or reoccurring atelectasis.
      The effectiveness of second research was to 84%. It's important to add that
      mostly patients with serious chest injury were subjected to unresolved or
      reoccurring atelectasis. And mainly in these cases blood was seen through the
      tracheobronchial tree lumen.

PMID- 24749267
TI  - [Case of successful thrombolytic therapy in complex cardio-pulmonary
      resuscitation for massive pulmonary thromboembolism in parturient after elective
      caesarian operation].
AB  - Pulmonary thromboembolism is a main cause of parturient mortality in the world.
      Recently there are few reports about a thrombolytic therapy use in parturient in
      medical publications. The article deals with a case of successful application of
      thrombolysis in a complex cardio-pulmonary resuscitation in parturient with
      massive pulmonary thromboembolism. Unexpected dyspnea and hypotension occurred in
      the 30 years old woman after elective caesarian operation. Syndrome S1-Q3 was
      fixed on an ECG monitor. Cardiac arrest was fixed in 10 minutes later.
      Streptokinase was administrated in a 1 hour after beginning of the resuscitation.
      Haemodynamic parameters recovered almost after the administration of
      streptokinase. Severe uterine bleeding occurred in 20 minutes after the
      administration. Uterine extirpation and tight tamponade of the small pelvis was
      performed for the bleeding stopping. Later a floating thrombus was diagnosed in
      the right femoral vein. Tromboectomy was performed. Convulsions had place on
      first and second day after the resuscitation. Cerebral edema was diagnosed by
      computed tomography. Consciousness occurred on the fourth day and the woman was
      weaned from the ventilator on the fifth day. The patient was discharged from the
      hospital on 20th day without neurological complications.

PMID- 24749268
TI  - [Modern principles of safety in erythrocytes-containing donor blood components
      transfusion].

PMID- 24749269
TI  - [Heparin-induced thrombocytopenia: theory and practice].
AB  - The article deals with detailed information about etiology, pathogenesis,
      clinical signs, prophylactics and treatment of a heparin-induced
      thrombocytopenia.

PMID- 24749270
TI  - [Anticoagulant therapy in pregnant women with mechanical prosthetic heart valves.
      Review of international clinical guidelines].
AB  - Recently thromboembolic and hemorrhagic complications are main causes of maternal
      morbidity and mortality. Normal pregnancy is associated with ahypercoagulation.
      This condition is complicated if the patient has a mechanical prosthetic heart
      valve. Therefore an anticoagulant therapy in these patients is a challenging
      task. Effects of anticoagulant drugs on the fetus, pregnancy and delivery must
      also be taken into consideration. The review deals with international clinical
      guidelines. Diagrams of anticoagulant therapy in pregnant women with mechanical
      prosthetic heart valves using direct (unfractionated and low-molecular-weight
      heparins) and indirect (warfarin) anticoagulants are presented in the review.

PMID- 24749271
TI  - [Clinical recommendations. Perioperative care for patients with underlying
      ischemic heart disease].

PMID- 24749272
TI  - [Electronic deficit as a possible health risk factor].
AB  - There is presented the analysis of medical-demographic situation in Russia, and
      the increase in population mortality is shown both to be associated with the
      degradation of the geosphere and alongside with other factors determined by the
      change in the electronic state of the environment. On the base of the
      interrelationship between the electronic saturation of the environment and an
      increase in population mortality and morbidity there is established a such risk
      factor for human health and life, which may currently become one out of
      significant, videlicet, the electronic deficit. In conditions of its appearance
      there are proposed options solving this problem by means of elaboration of the
      scientific rationale for the impact of the electronic deficit on the human
      organism and the creation of technologies providing environmental--medical safety
      of the population by virtue of the correction of the electronic state of the
      human habitat, food and drinking water and the implementation of the system for
      monitoring electronic abundance of the environment.

PMID- 24749273
TI  - [The value of housing conditions and urban environment for the health].
AB  - Housing and urban environments represent the physical context for everyday life
      and have a significant impact on population health and well-being. Depending on
      the quality of housing and urban conditions, they can support or restrict the
      health of their residents through a variety of aspects such as air pollution,
      noise, thermal conditions, safety aspects and environmental contamination.
      Therefore, housing and urban conditions are important dimensions for
      environmental health and knowledge on the main risk factors and their associated
      health effects is needed to identify adequate interventions and measures in the
      home and urban environment. This paper summarizes the results of WHO work on the
      health relevance of housing and urban environments and describes the health
      impact of the major risks observed in human settlements.

PMID- 24749274
TI  - [Disinfection of water: on the need for analysis and solution of fundamental and
      applied problems].
AB  - In the paper there is presented an analysis of hygienic--medical and
      environmental aspects of water disinfection as exemplified of chlorine and
      chlorine dioxide (CD). The concept of persistent multivariate risk for aquatic
      pathogens, the own vision of the mechanism of formation of chlorine resistance of
      bacteria under the influence of biocides based on a two-step process of
      information and spatial interaction of the receptor and the substrate, the
      hypothesis of hormetic stimulating effect of residual active chlorine (in the
      complex with other factors) on the growth of aquatic pathogens have been
      proposed. The aggravation of the significance of halogen containing compounds
      (HCC) as byproducts of water chlorination in terms of their potential danger as
      toxicants and carcinogens has been substantiated. Analysis of hygienic and
      medical and environmental aspects of the use of chlorine dioxide as a means of
      disinfection of water allowed to justify chemism of its biocidal effect and
      mechanisms of bactericidal, virucidal, protozoocidal, sporicidal, algacidal
      actions, removal of biofilms, formation of disinfection byproducts. Chlorine
      dioxide was shown both to provide epidemic safety of drinking water due to its
      high virucidal, bactericidal and mycocidal action and to be toxicologically
      harmless in the context of the influence on the organism of laboratory animals as
      well as in relation to aquatic organisms under the discharge of disinfected
      wastewater. There has proved the necessity of the close relationship of
      fundamental and applied research in performing the first in terms of depth study
      of microbiological, molecular genetic and epidemiological problems of
      disinfection (chlorination) of water and the implementation of the latters by
      means of the introduction of alternative, including combined, technologies for
      water treatment and disinfection.

PMID- 24749275
TI  - [Results of health risk assessment due to exposure to contaminants in drinking
      water in Russia population (review of literature)].
AB  - With the purpose of the analysis of general trends in the development of risk
      assessment methodology in Russia the results obtained with the her help, as well
      as existing methodological problems, there was performed a review of 68 published
      works concerning the assessment of the health risk for population under the
      exposure to chemicals in drinking water carried out in 42 cities and regions of
      the country. There was made the grouping of Russian cities on individual
      carcinogenic risk level and ranking on the values for the population carcinogenic
      risk. A list of prioritized carcinogens in tap water has been made. By the values
      of the risk indices to adverse effects of chemicals tap water there are exposed
      central nervous system, kidneys, liver, skin and mucous membranes, blood, bone,
      immune system, hormone homeostasis, blood circulation and digestion organs. There
      are identified methodological problems leading to an underestimation of the
      actual risk to public health under exposure of chemicals in drinking water: there
      are no used regional and age differences in exposure factors, virtually there is
      no assessed health risk for children population; there is ignored age sensitivity
      to carcinogens, there is rarely estimated exposure for all the real exposing
      routes of income and there are no carried out risk calculations at the upper
      limit (90- 95th percentile) of the exposure.

PMID- 24749276
TI  - [Epidemiological analysis of the dynamics and structure of population mortality
      rate from malignant neoplasms in the city of Tomsk].
AB  - There was revealed the tendency of reduction of cancer mortality in the city of
      Tomsk. Average indices of the time series of total mortality (absolute growth and
      growth rate) in 1998-2003 outstripped the similar indices in 2004-2010
      respectively 5.3 times and 1.6 times over. Mortality from cancer neoplasmas on
      localization decreased by 2 orders of magnitude. Mortality from cancer of the
      trachea, bronchus and lung in the structure of total oncomortality is on the 1st
      place, on the 2nd--the death rate from cancer of the stomach, on the 3rd place in
      1998-2003, mortality rate of colorectal cancer in 2004-2010. There was found the
      relationship of mortality of cancer of separate localizations with industrial
      emissions (leukemia), motor vehicles (cancer of the lips, mouth, pharynx, and
      colon) and stationary sources (cancer of the urinary organs). The air pollution
      with formaldehyde and particulate matter were established to affect the death
      rate for cancer of lips, mouth and throat, and other digestive organs and larynx.

PMID- 24749277
TI  - [Polycyclic aromatic hydrocarbons content in Antarctica soils as exemplified by
      the Russian polar stations].
AB  - The comprehensive study of the qualitative and quantitative composition of
      polycyclic aromatic hydrocarbons (PAHs) in soils of Antarctica (reference
      landscapes--mountains Hudson, Haswell Archipelago contaminated soil--Mirny,
      Druznaya-4, Bellingshausen--and imported soils) was performed with the use of
      HPLC in a gradient mode. A characteristic feature of the studied PAHs content of
      soils is the predominance of low-molecular polyarenes in them. Due to
      anthropogenic pollution the quantitative accumulation of both light and heavy
      PAHs occurs under the qualitative increase in the proportion of heavy polyarenes.
      Polyarenes pool in the studied soils is represented mainly by light PAHs:
      naphthalene, phenanthrene, fluoranthene, pyrene, etc. The content of
      benzo(a)pyrene does not exceed the MCL (adopted in the Russian Federation) for
      this ecotoxicant. Performed primary factual and statistical analysis of data
      permitted to reveal that heavy PAH pollution of Antarctica soils is in the most
      initial stage, there is no sustained and statistically significant accumulation
      of PAHs in soils of maritime as well as continental Antarctica. There are
      established the levels of the actual content of various PAHs in soils of
      different regions of the Antarctica, which is the basic data for further
      comparative analysis of data of geochemical studies.

PMID- 24749278
TI  - [Influence of exposure to persistent toxic substances (PTS) on pregnancy outcomes
      in indigenous females of Chukotka].
AB  - No associations of enhanced blood levels of persistent organic pollutants (POPs)
      and metals with premature births and low birth weight have been revealed;
      regarding POPs an inverse but not statistically significant relationship was
      noted. Maternal blood levels of POPs were higher in cases of stillbirths and
      congenital malformations. Nevertheless no increased relative risk of adverse
      pregnancy outcomes has been revealed in regard to any PTS and the dose range.
      More exposed to polychlorinated biphenyls (PCBs) and other POPs females gave
      birth to girls more often. Higher POPs blood levels were noted in females with
      earlier menarche, shortened menstrual cycle and prolonged menstrual bleeding.

PMID- 24749279
TI  - [Influence of the consumption of radioactive contaminated food on the formation
      of the irradiation levels and health of the inhabitants of radioactive
      contaminated regions of Ukraine].
AB  - Within all these years after the Chernobyl disaster the population of
      contaminated areas of the Rivne region was shown to consume radioactive
      contaminated foodstuffs. The main components of the formation of the internal
      irradiation of the population in them were and remain locally sourced milk and
      meat, forest mushrooms and berries. After 1991, the largest annual internal doses
      in persons observed in 1997 varied from 2,2 to 1,45 mSv/year and in 2011--in the
      inhabitants of the village of El'no they were yet reaching 1.43 mSv/year. After
      2003, exposure levels in most inhabitatants of affected areas exceeded the
      criterion specified by national legislation for residents of the tightened
      radioecological control zone (0,5 mSv/year). The long-term residence in the
      contaminated area, elevated levels of chronic internal exposure, lack of
      radioactively sound foodstuffs and involuntary consumption in 1987-2011
      radioactively contaminated food of local production were noted to led to an
      increase in general morbidity, and incidence of endocrine diseases rate and their
      separate nosological forms.

PMID- 24749280
TI  - [Comparative analysis of the influence of nano- and ionic forms of silver on
      biochemical indices in laboratory animals].
AB  - A comparative analysis of the effect of silver nanoparticles (SNP) with a
      diameter of 14 nm and silver sulfate (SS) on biochemical indices of the state of
      the organism under the administration of preparations with drinking water to mice
      F1 CBAxC57Bl (from 0.1 to 500 mg Ag/l for 2 weeks) and nonlinear rats (from 0.01
      to 5 mg Ag/l within 6 months) has been performed In the experiment on mice there
      was found an increase in activity of glutathione reductase (GR) in erythrocytes
      under the administration of both drugs and reduction of antiradical activity of
      serum--under the introduction of SNP only. The administration of low doses of SNP
      in the experiment on rats caused much less pronounced changes in serum markers of
      the state of the liver; kidneys, protein and lipids metabolism in comparison with
      equivalent doses of the SS, that as a whole with the qualitative differences on
      GR activity in erythrocytes satisfactorily was explained by activation of
      phagocytic cells with nanoparticles. Thus, for the first time the SNP biological
      effects in animals were shown to be caused both by the exposure to solubilized
      Ag+ ions and by the response of cells to the surface of the nanoparticles
      themselves.

PMID- 24749281
TI  - [Morphofunctional cell assessment of dynamics of silver nanoparticles exposure on
      the rat liver].
AB  - There was investigated the dynamics of 1-, 3- and 6-month exposure to 4 doses of
      silver nanoparticles of size 14.3 +/- 0.05 nm stabilized with gum arabic, and 4
      doses of silver sulfate on the liver of male outbred rats by 13 cell
      morphofunctional indices. As the solvent to obtain a working solution there was
      used distilled water solutions of different conccentrations were obtained on the
      base of Moscow tap water cleaned out by a charcoal filter. The animals had free
      acccess to the drinkers with the studied water. For silver sulfate as a control
      intact rats served, for silver nanoparticles--acacia gum. The increase in the
      number of polyploid hepatocytes, micronekroses and discomplexation of hepatic
      beams and the decreasing the number of reticular endothelial system cells in the
      liver were shown to permit to evaluate the effect of 6-month nanosilver exposure
      to the liver at a dose of 0.3 mg/kg as pronounced harmful (Fel), 0.023 mg/ kg--as
      LOAEL, and 0.0028 and 0.0006 mg/kg--as NOEL. The effect of silver sulfate in
      doses of 0.28 and 0.03 mg/ kg is assessed as pronounced harmful (Fel), 0,0028
      mg/kg--as LAOEL and 0.0005 mg/kg--as NOEL. More earlier detection of toxicity of
      silver sulfate as Fel (at 3 months) and in smaller doses indicates its greater
      toxicity to the liver than silver nanoparticles.

PMID- 24749282
TI  - [Hygienic evaluation of the effectiveness of the concept of improvement the water
      supply in the south-eastern region of the Republic of Tatarstan].
AB  - In the paper there is presented the hygienic assessment of the effectiveness of
      the implementation of a program aimed at improving conditions of the water supply
      in the oil producing regions of the Republic of Tatarstan. As a result of
      realization of measures it was able to improve the quality of drinking water in
      terms of chemical safety and to reduce the risk to public health. For the present
      time the following factors: water quality of the water source, the mismatch of
      sanitary protective zone to requirements of sanitary laws and failure to comply
      with security measures on its territory, deterioration of water quality during
      transport and imperfection of laboratory control monitoring were shown to make
      the highest contribution to the disadvantage of centralized drinking water
      systems.

PMID- 24749283
TI  - [On the issue of optimization of adaptation process to new environment taking
      into consideration climate and weather conditions].
AB  - There are revealed the features in the registration of newly diagnosed morbidity
      in cases in the organized team out of number of persons constantly living in the
      conditions of Baltic Sea (Kaliningrad region), as well as in those coming from
      other parts of the Russian Federation. This stipulates the elaboration of
      measures for prevention of disadaptational shifts in the organism related with
      adaptational processes as well as the process of acclimatization.

PMID- 24749284
TI  - [Prevention research within the frameworks of public health programs in Ukraine].
AB  - There were shown the current approaches to the prevention of non-communicable
      diseases, the fundamental documents of the World Health Organization, legislative
      documents in Ukraine, aimed at the prevention of non-communicable diseases,
      detailed coverage of Interdisciplinary comprehensive program "Health of the
      Nation", the main objectives of the program, approaches to solving them in the
      implementation of the scientific part of the program by the government agencies
      of the national Academy of Medical Sciences of Ukraine, principles for the
      selection of research works, the results of the accomplishment of the research
      works within the frameworks of the public health program and the prospects for
      their implementation with taking into account preventative direction.

PMID- 24749285
TI  - [Clinical hygienic substantiation for the individual biocorrection of
      ecologically dependent conditions in the critical population groups industrial
      areas of Ukraine].
AB  - In the article there is considered the problem of environmental and human body
      pollution with heavy metals, the effectiveness of individual biocorrection in
      critical population groups--pregnant females and children residing in
      technologically contaminated areas. It was established that, in spite of the
      correspondence of the content of abiotic heavy metals to their MACs in the
      environment, the concentration of lead and cadmium in the internal environment of
      the organism is 1,6-15,4 times larger than physiological norms and accompanied by
      substantial deficiency of essential trace elements. The similar situation in
      children was proved to cause the fall in mental capacity and learning ability, in
      pregnant females--to various complications. The obtained results were the
      scientific substantiation for the feasibility of performing of biocorrection for
      trace elements imbalance and ecologically dependent conditions in the population
      of the industrial region, proved its high clinical and hygienic efficiency, which
      is the basis for the wide introduction of pectin containing preparations with the
      aim to enforce the health, prevent ecologically dependent conditions and
      increasing the adaptive capacity of the organism.

PMID- 24749286
TI  - [Complex strategies for management of child health in districts of endemic iodine
      deficiency in the Saratov region].
AB  - In the article there is presented an analysis of clusters of the formation of
      iodine deficiency in schoolchildren of the Saratov region. There is given a
      hygienic assessment of iodine content in food raw materials and food, grown and
      produced in the territory of the region. For various groups of food the low
      content of trace element iodine was shown to be typical. The analysis of the
      quality and diversity of iodized salt sold in the trading network of the region
      has been performed. The formation of the mass iodine deficiency states in the
      Saratov region was shown to bear a longtime character According to the results of
      urine screening studies of examined children of organized groups an average level
      of iodine deficiency has been revealed.

PMID- 24749287
TI  - [Forecast of costs of ecodependent cancer treatment for the development of
      management decisions].
AB  - The methodical approach for probabilistic forecasting and differentiation of
      treatment of costs of ecodependent cancer cases has been elaborated. The modality
      is useful in the organization of medical aid to cancer patients, in developing
      management decisions for the reduction the occupational load on the population,
      as well as in solutions problems in compensation to the population economic and
      social loss from industrial plants.

PMID- 24749288
TI  - [Evaluation of the functional state of drivers by parameters of vegetative
      regulation of cardiac rhythm with the use of method of wireless
      cardiorhythmography].
AB  - Analysis of heart rate variability (HRV) provides the possibility to obtain the
      predictive and meaningful information on the functional status and features of
      adaptive responses of the whole organism. Monitoring the functional state in the
      course of professional activities with the use of wireless cardiorhythmography
      provides data acquisition on heart rate dynamics in accordance with the level of
      occupational load. The article is devoted to the development of methods for rapid
      assessment of the functional state of motor vehicle drivers in the process of
      occupational activity. There was performed the hygienic assessment of working
      conditions of jobs. The studies of the influence of the factor loadings on the
      level of the functional state of the cardiovascular system (CVS) of drivers were
      performed with the help of wireless telemetry system. A developed computer
      software were used for the calculation of the spectral parameters of HRV. By the
      analysis of cardiorhythmograms in drivers there were both revealed significant
      disorders of the rhythm of the cardiac activity (reduction of total power TP, HF
      component, increase in LF-component, LF/HF index, extrasystole) and recorded
      changes in the spectral HRV indices in accordance with the level of occupational
      load, that represents the degree of individual response. The method of wireless
      cardiorhythmography is promising for the creation of personalized monitoring
      system to assess the risk of individual occupational risk.

PMID- 24749289
TI  - [Smoking as an additional risk factor for the staff of chemically hazardous
      production facilities].
AB  - One of the factors that increase the risk of genotoxic effects in the staff of
      chemically hazardous production facilities is smoking. There was performed the
      cytogenetic study in 104 males working with highly toxic chemicals, 71 people out
      of which were smokers and 33--non-smokers. No statistically significant
      differences were revealed between groups of smokers and nonsmokers. Among smokers
      39 males smoked more than 15 cigarettes per day and were referred to the group of
      "heavy smokers", 32 cases were light smokers (less than 15 cigarettes per day).
      The level of chromatid exchanges and exchange of chromosomal aberrations
      (dicentric and ring chromosomes, atypical atypical monocentrics) in the group of
      "heavy smokers" were shown to be significant higher than in non-smokers and light
      smokers groups. Our data confirm the synergistic effect of smoking and the
      factors of increased chemical hazards.

PMID- 24749290
TI  - [Psychoemotional state and peculiarities of mental working capacity preschool
      children with mental retardation].
AB  - The study is devoted to the investigation of the mental and emotional state and
      mental capacity of preschool children (6-7 years) with the mental retardation
      (MR). Under observation there were 87 children with MR. Mental performance of
      children with MR was found to be determined by their psycho-emotional state.

PMID- 24749291
TI  - [Assessment of children's health risk posed by traffic-related air pollution as
      exemplified by the city of Salekhard].
AB  - With the aim of determination of the levels of children's health risk from
      chemical air pollution caused by vehicle emissions, on the territory of the
      municipal district of the city of Salekhard there was carried out the work on the
      study of the intensity and the chemical structure of traffic-related air
      pollution in the locations of 16 children's preschool institutions. There was
      used the technique of the counting campaign for the structure and intensity of
      road traffic flows, children's health detriment was calculated according to the
      method of risk assessment. The main danger in the emissions of vehicles is
      belonged to nitrogen dioxide (43.6%), benzo(a)pyrene (37.4%), carbon monoxide
      (6.57%), formaldehyde (4.43%). Being detected at the level of I0(-4)-10(-5) and
      corresponding to the maximum permissible risk estimated cancer risk is a subject
      for continuous monitoring.

PMID- 24749292
TI  - [Results of biomonitoring for zinc in children of the Irkutsk region].
AB  - The aim of the work is to test the application of the method of evaluating the
      content of zinc in the hair of the child population for solving SHM tasks on the
      example of the Irkutsk region. In total 426 children aged 5-6 years were
      examined, selected in four groups. The first group was consisted of children
      residing in a large industrial center to the south of the region, the second--in
      the the small town of the central part, the third group was formed by rural
      children of the central region, and the fourth--the northern and foothill
      regions. Hair analysis was performed by atomic absorption method. Found that zinc
      content in hair was established to be prone to significant variability. In
      children of the southern industrial center of the region (Group 1) there was
      noted the least amount of zinc (median is of 65.6 mg/kg). In 53% of the samples
      the element content was below the absolute norm (AN), out of which 25% below the
      biologically permissible limits (BPL). Only in 8.5% of the samples the zinc
      content exceeded AN and 3%-- BPL. In the range of AN there are 38% of the
      children, within the BPL range--71%. In the 2nd, the median of the concentration
      of zinc in the hair was 152.5 mg/kg. In the range of the AN there were 53% of the
      samples, in the BPL range--86% of the samples. Deviations from the reference
      levels were observed in the direction of exceedence of values. 36% of rural
      children (group 3) are provided with zinc within the limits of AN, 93%--within
      BPL. Only in 6% of children the zinc content in the hair below AN or BPL. In the
      4th Group only 7.7% of samples were in the AN range and 27% of the samples--in
      the BPL range. 92% of the samples were way beyond the limits of AN and 73%-
      beyond the BPL. In most of the samples the higher content of zinc was observed.
      The highest concentrations of zinc in hair were observed in children living in
      the northern foothills and the Irkutsk region, which are characterized by
      elevated levels of this metal in the soil. In the diet of the inhabitants of
      these regions there is prevailed local food of animal origin, which is the main
      source of the entry of zinc into the body. In areas of intensive industrial
      development, despite the rather high zinc content in the objects of the
      environment, there was noted the high frequency of the zinc deficiency states,
      especially in conditions of complex chemical factors exposure and lifestyle that
      may be associated with features of not only input, but also the absorption of
      zinc in the body children.

PMID- 24749293
TI  - [Some aspects of prevention activity of the teacher, directed to the improvement
      of the health of schoolchildren].
AB  - The problem of bottom quality of prevention work directed to the saving and
      strengthening the health of schoolchildren, today is a very urgent and requires a
      joint activity of the pedagogical and medical community. In the article there are
      presented data proving the feasibility of an active teacher's work on the
      formation of health saving space in a present school. Conspicuous is the interest
      of schoolchildren to the problems of a healthy lifestyle during performance of
      interesting preventive measures with them and as a result risk mitigation
      subsequently. At the same time, there was noted a low level of training teachers
      in various fields (including biologists) on specialized problems of the
      prevention of healthy lifestyles, which points to the need for introduction into
      the curricula of higher educational institutions additional modules on health
      saving, as well as conducting training courses involving health care workers as
      for teachers as parents.

PMID- 24749294
TI  - [Diagnosis of the territories with the use of integral indices of chemical
      contamination of soil and grounds, relied on the background and hygienic
      standards].
AB  - Analysis of the efficiency of diagnosis of lands for different functional
      appropriations with integral indices of chemical contamination of soils and
      grounds under different environmental conditions showed: the greatest accuracy of
      the information about the structure and degree of contamination of territories is
      provided by the index relying on hygienic standard (index of soil contamination,
      ISC). The number of hygienically dangerous lithochemical anomalies revealed by
      ISC is several times more than the fixed by the index of total pollution of soils
      by trace elements (Zc), focused only on their background levels. Index Zc is in
      many respects subjective and unacceptable in complex soil geochemical conditions
      where the selection of the regional background is impossible. ISC account not
      only in trace elements, but other hygienically regulated substances (As, Hg,
      mobile forms of metals, water-soluble salts, carbohydrates, etc.) either.

PMID- 24749295
TI  - [Methodological approaches to the hygienic evaluation of total artificial
      lighting of classrooms with different light sources on the basis of the response
      of the cardiovascular system of schoolchildren].
AB  - Hygienic evaluation of innovative equipment in educational institutions requires
      the use of appropriate methods permitting to establish valuable criterias for the
      effectiveness of the application of new technologies. The study of the response
      of the cardiovascular system of schoolchildren under using different light
      sources allowed to establish the increase in adaptive capacities and the
      improvement of the functional state of the organism in LED in comparison with
      fluorescent lighting.

PMID- 24749296
TI  - [Features of adaptive responses in right-handers and left-handers, and their
      relationship to the functional activity of the brain].
AB  - In the article there is considered the relationship between adaptation state of
      the organism and features of bioelectric activity of the brain in right-handers
      and left-handers. Practically healthy persons of both genders, 23-45 years of
      age, with the chronic stress disorder were examined. Adaptation status was
      evaluated with a computer software "Anti-stress", features of bioelectric brain
      activity were detected by means of spectral and coherent EEG analysis, also the
      character of motor and sensory asymmetries was determined. The obtained data
      showed that the response of the organism to excitators of varying strength is a
      system one and manifested at different levels; adaptation status and
      bioelectrical activity in right-handers and left-handers have features.

PMID- 24749297
TI  - [Effects of quantum nonlocality in the water activation process].
AB  - The dynamic alterations of the magnetic flux density of the water volume,
      activated with structurally stressed calcium carbonate in micellar form have been
      investigated. The phase of the associated water was established to exhibit
      electrical and magnetic properties, recorded by in B&E meter in the frequency
      range of 5Hz - 2kHz. Alterations in water Eh (redox) potential and the magnetic
      flux density B testify to synchronous auto-oscillatory changes. This gives
      evidence of non-linearity of the relationship between auto-oscillatory processes
      excited in the water; and reflects the nonlocal in time the relationship between
      the states of water, manifesting in a change of water activity on the 1st and 2nd
      day in negative time. The mechanism of action of associated water phase is shown
      to be described by de Broglie concept of matter waves with taking into account
      delocalized in time states of phase of electron wave packet in accordance with
      the transactional interpretation of quantum physics.

PMID- 24749298
TI  - [Justification of regulations for the use of computers with LCD monitor during
      academic studies].
AB  - In the article there are reported the results of studies of the effect on the
      functional state of the body of schoolchildren curriculum with the use of
      personal computers with LCD monitors. The resistance to the development of visual
      and general fatigue in schoolchildren -users of personal computers with LCD
      monitors was found to be higher because they provide a more favorable environment
      for visual work in comparison with monitors based on cathode-ray tube. The use of
      LED lighting in classrooms contributes to the creation a more favorable light
      environment than in fluorescent lighting and reduces fatigable impact (both
      general and visual) of classes with the use of personal computers.

PMID- 24749299
TI  - [Scientific approaches to modernization of the regulatory framework in the field
      of hygiene of planning and building of settlements in Ukraine].
AB  - In the paper there are investigated and analyzed the new laws and regulations of
      sanitary and town planning legislation, introduced in 2011-2012 which concern
      issues of planning and building of settlements. It is established that the
      functions of the State for Sanitary and Epidemiological Oversight have been given
      up and the necessity of incorporation in the Law of Ukraine "On ensuring sanitary
      and epidemiological welfare of the population" alterations which touch upon the
      implementation of a new approach to the State Sanitary and Epidemiological
      Oversight of the objects, namely for the placement of objects with low and
      moderate epidemic risk accordingly to hygienic declarations, objects with high
      risk--using an approach directed to the risk assessment of the impact of such
      facilities on public health.

PMID- 24749300
TI  - [Anaesthesia for patients with obstructive airway diseases].
AB  - Obstructive lung diseases like asthma or chronic obstructive lung diseases have a
      high prevalence and are one of the four most frequent causes of death.
      Obstructive lung diseases can be significantly influenced by the choice of
      anesthetic techniques and anesthetic agents. Basically, the severity of the COPD
      and the degree of bronchial hyperreactivity will determine the perioperative
      anesthetic risk. This risk has to be assessed by a thorough preoperative
      evaluation and will give the rationale on which to decide for the adequate
      anaesthetic technique. In particular, airway instrumentation can cause severe
      reflex bronchoconstriction. The use of regional anaesthesia alone or in
      combination with general anaesthesia can help to avoid airway irritation and
      leads to reduced postoperative complications. Prophylactic antiobstructive
      treatment, volatile anesthetics, propofol, opioids, and an adequate choice of
      muscle relaxants minimize the anesthetic risk, when general anesthesia is
      required In case, despite all precautions intra-operative bronchospasm occurs,
      deepening of anaesthesia, repeated administration of beta2-adrenergic agents and
      parasympatholytics, and a single systemic dose of corticosteroids represent the
      main treatment options.

PMID- 24749301
TI  - [Predictive value of body mass index for perioperative hyperglycemia occurrence
      in cardio-surgical patients without diabetes mellitus].
AB  - Purpose of the study was to assess a predictive value of body mass index for
      perioperative hyperglycemia occurrence in cardio-surgical patients without a
      diabetes mellitus. MATERIALS AND METHODS: Retrospective analysis of glycemic
      profile, frequency and level of perioperative hyperglycemia was performed 120
      patients without a diabetes mellitus, undergoing elective cardiac surgeries with
      cardiopulmonary bypass were included in the study. All patients were divided into
      three groups. Group-1 included patients with normal body weight (body mass index
      (BMI) < 25), Group-2--patients with increased body weight (BMI 25-29.9), Group-3-
      patients with obesity (BMI > 30). RESULTS: Elective cardiac surgeries with
      artificial circulation accompanied with episodes of hyperglycemia. Hyperglycemia
      occurrence did not have relation with initial glycemic profile of the patients.
      Glycemia level increased during surgery and the highest levels of both glycemia
      increasing of hyperglycemia frequency were fixed during cardiopulmonary bypass
      and postperfusion period. Increased body weight and obesity are predisposing
      causes of perioperative hyperglycemia.

PMID- 24749302
TI  - [Coagulation profiles during cardiac surgery].
AB  - OBJECTIVE: To evaluate patients' hemostasis after cardiac surgery using
      thromboelastometric and impedance aggregometry. MATERIALS AND METHODS: 66
      patients were examined intraoperatively. Comparison group included 45 blood
      donors. Hemostasis was tested for thromboelastometricRotem Gamma with the
      assessment of external (exTem) and internal (inTem) pathways of coagulation tests
      performed detection of heparin (hepTem) and cytochalasin-D-inactivation of
      platelets (fibTem) to assess the level of fibrinogen. Collagen-induced platelet
      aggregation was determined in an aggregometer CHRONO-LOG (USA). RESULTS:
      Significant deviations of the parameters of hemostasis were detected in 52 of the
      66 studied patients. In group-1 (23 patients) revealed a residual effect of
      heparin. The effect manifested prolongation CT (clotting time) inTem to an
      average of 241 +/- 15 s, compared with CT hepTem--181 +/- 7. Patients in this
      group were in need of additional administration of protamine sulfate.
      Postoperative bleeding and resternotomia were observed in 3 patients of group-1.
      In group-2 (25 patients) CT inTem was 216 +/- 21 with significantly fewer CT
      hepTem (272 +/- 26). The data indicated excess of protamine sulfate. Platelets
      aggregation decreased compared to the norm. According to the obtained results,
      the addition of protamine sulfate is not required, however, in 7 cases the
      protamine sulfate was administered in a dose of 8.9 +/- 0.8 mg in 6 cases
      resternotomiya required. In the third group (n = 6) bleeding was observed in 4
      patients. The difference in CT-hepCT was significant. Significant variations were
      revealed in the tests of the activity of the extrinsic pathway of coagulation and
      cytochalasin-D-induced inactivation of platelets: exMCF- 42 +/- 2 mm (normal 57
      +/- 15 mm), fibMCF 5.0 +/- 0.3 mm (norm 12.8 +/- 4.3 mm). The concentration of
      platelets and their aggregation activity was sharply reduced. Disorders of
      hemostasis in the third group, designated as dilution coagulopathy. CONCLUSION:
      Turning thromboelastometric and impedance aggregometry in the study of the
      coagulation profile of patients undergoing cardiac surgery in postperfusion
      period brings valuable information and allows a differentiated treatment of
      hemostasis disorders.

PMID- 24749303
TI  - [Epidural analgesia in the first stage of labor--is there an alternative?].
AB  - OBJECTIVE: To evaluate the influence of epidural analgesia and lumbar
      paravertebral block on the structure of the delivery, the fetus and newborn, and
      the quality and duration of analgesia. MATERIALS AND METHODS: Patients were
      randomized into three groups, 30 patients in each group. In the group-1 patients
      received epidural analgesia (EA), in the group-2--paravertebral block (PVB), in
      the group-3 patients refused pain relief in labor. Pain was assessed by VAS.
      Length of the first and second stage of labor the impact on the CTG and fetal
      blood gases from the umbilical cord of newborns in the first minute of life were
      fixed. Data were analyzed by Mann-Whitney U test and presented as median (25th
      75th percentiles). RESULTS: In both groups of patients in pain reduction was
      significant adjustment contractions and after 1 hour was 94.5% in EA, and PVB
      group--78.7% of the initial values. Under EA opening cervix was statistically
      significantly greater than in the PVB (192.5 (145, 302) vs 172.5 (112, 210) min)
      p < 0.05. Second stage of labor was also shorter in the PVB than in the EA (30.4
      (10.2, 46.5) vs 59.8 (40.2, 81.5) min), in the control group it was--40.6 (21.3,
      55.4) min, p < 0.05. PVB was observed in the group of more stable hemodynamics
      than in the EA for the entire period of observation. There were no adverse
      effects on the fetus and the newborn in the arms of the study. CONCLUSION: The
      proposed lumbar paravertebral block is simple to perform, is effective in
      reducing pain in the first stage of labor does not require continuous hemodynamic
      monitoring may be used for the treatment of birth dystocia and is a good
      alternative when the use of epidural analgesia during labor is limited.

PMID- 24749304
TI  - [Effect of preoperative infusion volume on frequency of intraoperative nausea and
      vomiting as complications of spinal anaesthesia in pregnant women during
      caesarian operation (pilot study)].
AB  - Purpose of the study was to define a prophylactic effect of different preload
      volumes on the rate of intraoperative nausea and vomiting (IONV) as a
      complication due to spinal anaesthesia (SA) during caesarian operation (SO) in
      parturient. Data for analysis was collected during clinical observational multi
      center research included several medical centers. Statistics involved originally
      developed method allowed to analyze relative risk changing along the entire
      interval of all applied preload volumes. The results suppose that preload is
      effective method of IONV prophylactics in parturient during SO under SA if only
      infused preload volumes do not break specially determined limits of effective
      interval. If preload volume value is out of this range then preinfusion may lead
      to increasing risk of IONV occurrence.

PMID- 24749305
TI  - [Problem of treatment for pyo-inflammatory complications caused by
      Acinetobacter].
AB  - The article deals with analysis of a detection frequency and antibacterial
      treatment resistance of Acinetobacter spp.of different species affiliation.
      Strains of bacteria detected in patients with pyo-inflammatory complications
      after surgeries (period from 2010 to 2012) were involved in the study 137 strains
      of Acinetobacter spp. were detected and studied Fraction of Acinetobacter spp. in
      2010, 2011 and 2012 was 2.3, 3 and 3.4% respectively. Fraction of P. aeruginosain
      all non-fermentative Gram-negative bacteria (NFGNB) decreased by 120% and
      fraction of Acinetobacter spp. increased by 200-250%. Acinetobacter spp.
      detection frequency was not significantly changed in the period from 2006 to
      2012. However the fraction of Acinetobacter spp. in NFGNB increased by 150% and
      was 29% in 2012. Detection frequency of A. baumanii sharply increased in 2012. A
      study of antibacterial treatment resistance of Acinetobacter spp. (10
      antibacterial medicines) showed that Polymyxin B and E (Colistin) was the most
      effective medicine for A. baumanii and A. calcoaceticus infection. 85-95% of
      Acinetobacter spp.strains kept sensitivity to this antibacterial medicine. 66
      88.9% of A. baumanii strains, 66.7-81.8% of A. alcoaceticus and 66.6% of other
      Acinetobacter spp. were sensitive to Tigecycline. Dioxidine effectiveness was
      close to Tigecycline in 66.7-80% of A. baumanii strains. 85-100% of A.
      calcoaceticus strains were sensitive to Dioxidine. There is a trend of decreasing
      of A. baumanii sensitivity to Carbapenems by 200%. Fraction of strains sensitive
      to Meropenem and Imipenem in 2012 was 21.4% and 16.7% respectively. All studied
      strains of A. lwoffi and A. haemolyticus kept sensitivity to Carbapenems. In 2012
      23.8% of A. baumanii and 50% of A. calcoaceticus strains were sensitivity to
      Amikacin, meanwhile A. lwoffi and A. haemolyticus were not sensitive to this
      medicine. 31.3% of A. baumanii and 50% of A. calcoaceticus strains were sensitive
      to Ceftazidime/Sulbactam. 5.3% of A. baumanii and 15.8% of A. calcoaceticus
      strains were sensitive to Piperacillin/Sulbactam. Gentamicin effectiveness was
      fixed in 12.5% of A. baumanii and 45.5% of unidentified Acinetobacter-strains.
      Gentamicin was not effective against A. lwoffii and A. haemolyticus. Thus
      Polymyxins (in monotherapy or in combination with glycopeptides), Dioxidine and
      Tigecycline in combination with Carbapenems or Cefiazidime/Sulbactam are to be
      drugs of choice in treatment for pyo-inflammatory complications caused by
      Acinetobacter spp.

PMID- 24749306
TI  - [Evaluation of haemostasis and endothelial dysfunction characteristics in patient
      with community-acquired pneumonia].
AB  - The article deals with a study of hemostasis (D-dimer soluble fibrin-monomer
      complex, time fibrin self-assemblance, antitrombin III, fibrinogen), endothelial
      dysfunction (f. Willebrand and activity of plasminogen activators inhibitor type
      1) and CRP in 61 patients with CAP in the day of admission and before discharge
      from hospital 17 patients had a severe pneumonia, 6 people died. The levels of
      all markers (except AT-3) were increased on admission and were reduced before
      discharge, but within the normal range to include only FW, CRP and time fibrin
      self-assemblance. DD, CRP and PAI-1 were dependent on the severity of the CAP,
      severity of SIRS and extent of the inflammatory process. The risk of severe
      pneumonia increased with the level of D-dimer in the onset of the disease more
      than 2.0 mkg mL(-1) (OR = 21.8, 95% CI: 3.09-154.8), with the results of TP-test
      less than 0.5 (RR = 2.68, 95% CI: 1.23-5.84), with CRP greater than 200 mg l(-1)
      (OR = 4.6, 95% CI: 1.87-11.45) and PAI-1 activity more than 30 U l(-1) (OR =
      2.05, 95% CI: 0.88-4.74). Rg-CAP outcomes best reflect the level of DD, measured
      prior to discharge patients.

PMID- 24749307
TI  - [Prophylaxis of intraoperative nausea, vomiting and abdominal discomfort due to
      spinal anaesthesia for caesarian operation].
AB  - The article deals with data of comparison of different antiemetic drugs used for
      prophylactics of intraoperative nausea and vomiting (IONV) during caesarian
      operation. 150 women included in the study were divided into three groups.
      Patients of the group-1 (80 women) received dproperidol 0.08-0.12 mg kg(-1)
      intravenously and atropine 0.006-0.009 mg kg(-1). Patients of the group-2 (50
      women) received dexamethasone 0.04-0.1 mg kg(-1) intravenously. In the group-3
      (20 women) patients received methoklopramide 0.1-0.2 mg kg(-1) intravenously.
      Intravenous administration of low doses of atropine and dproperidol provides the
      most effective prophylactics of IONV.

PMID- 24749308
TI  - [Postoperative analgesia with nefopam and non-steroidal anti-inflammatory drugs
      in patients after surgery for tumors of head and neck].
AB  - MATERIALS AND METHODS: 83 adult patients included in the study were divided into
      two groups. Patients of the group-1 (n-49) had medium level of pain after cancer
      head and neck surgery. Patients of the group-2 (n-34) had severe pain. Three
      first postoperative days their post-operative multimodal analgesia started with
      tenoxycam 20 mg i.m. after induction of anesthesia, then every 24 hour (58
      patients). 25 patients got ketoprofen 100 mg i.m. every 8-12 hours instead of
      tenoxycam. All patients had nefopam 30 mg i.m. 30 min prior the end of surgery
      procedure, and every 8 hours afterwards. 7 patients of the group-1 had more than
      4 pain scores (day 1), 4 patients--at the day 2. They received tramadol or
      paracetamol additionally. 7 patients (group-2) also had up to 5 pain scores on
      the day 1, 5 patients had 4 pain scores on the day 2, and 3 patients 4 pain
      scores on the day 3. All that patients received additional analgesia with
      tramadol or trimeperidine once a day. 8.4% of patients suffered from adverse
      reactions (tachycardia, PONV and sweating). CONCLUSION: This method of multimodal
      postoperative analgesia is very simple and fairly efficient.

PMID- 24749309
TI  - [Oxygen consumption in the lungs and systemic circulation--different methods of
      measurement of one data or different data?].
AB  - The article deals with calculation of oxygen consumption in the lungs by means of
      breathing gas mixture analysis and in parallel--in the systemic circulation by
      reverse Fick method; 32 paired measurements were performed in 8 patients after
      cardiac surgery with cardiopulmonary bypass. The mean pulmonary oxygen
      consumption was higher than the same value calculated by the reverse Fick
      principle--148.4 +/- 39.9 ml x min(-1) x m(-2) and 120 +/- 35.1 ml x min(-1) x m(
      2), respectively, the mean difference between two methods was 28.4 +/- 18.4 ml x
      min(-1) x m(-2). However, in two observations the interrelation was inversed.
      While analyzing physiological and methodological reasons for these differences,
      the authors concluded that, despite both methods can be used in monitoring
      systemic oxygen transport in the critically ill, they are not interchangeable,
      and valuable additional data could be derived from fast changes in lungs oxygen
      uptake.

PMID- 24749310
TI  - [Application of shot-latency cortical somato-sensory evoked potentials for
      evaluation of swallowing disorders in early period after posterior fossa
      surgery].
AB  - Main tasks of early postoperative period in patients after posterior fossa
      surgery are the timely and safe weaning from mechanical ventilation and
      extubation. For clinical assessment of the hypopharynx function we use an
      algorithm developed in the intensive care unit (ICU) of the Burdenko Scientific
      Research Institute of Neurosurgery. Disadvantages of the clinical test for
      assessment of patient's readiness for extubation are subjectivity and
      impossibility to use it in conditions of even superficial sedation. Shot-latency
      somato-sensory evoked potentials (SSEP) can be applied in conditions of sedation
      and objectify the brain stem deficit. The goal of the study was to define the
      changes of cortical SSEP in patients with disorders of swallowing after posterior
      fossa surgery. To assess the swallowing disorders we used a scale of swallowing
      disorders in intubated patients with brain stem damage. We compared results of
      cortical SSEP, test of swallowing disorders in intubated patients and clinical
      results of extubation. 17 patients with tumors of posterior fossa were included
      in the study. All patients were divided into two groups depending on duration of
      mechanical ventilation. Patients of the group-1 were successfully extubated in
      4.5 hours. Patients of the group-2 were mechanically ventilated more than 15
      hours because of impossibility to pass the test of readiness for extubation.
      RESULTS: Central conduction time symmetry index after the surgery was lower in
      the group-1 than in group-2. There was inverse correlation between amplitude of
      cortical response N20 and time from the patient's admission to the ICU until the
      moment of extubation. CONCLUSIONS: Asymmetry of central conduction time and
      decreasing of N20 amplitude can be used as additional predictor of swallowing
      disorder.

PMID- 24749311
TI  - [Severity of the lung disease index in infants with respiratory distress
      syndrome].
AB  - Optimization of respiratory support and prevention of ventilator-associate lung
      injure are the most important problems of neonatal resuscitation and intensive
      care. THE AIM OF THE STUDY: To improve the results of intensive care for
      respiratory failure in preterm infants by optimizing respiratory support on the
      basis of the analysis of the biomechanical characteristics of the lungs and blood
      gas. MATERIALS AND METHODS: The study included 138 infants with birth weight
      1500g (1300-1740g) and a gestational age of 30.5 (29-32) weeks in need of
      mechanical ventilation. Apgar score at one minute was equal to 5.0 (4.0-6.0)
      points, and the fifth--7.0 (6.0-7.0) points. Biomechanical properties of light
      investigated the dynamic lung compliance, aerodynamic upper airway resistance,
      the coefficient of hyperextension, the time constant and the coefficient of RVR,
      reflecting the patient's spontaneous breathing pattern were evaluated. RESULTS:
      It was found that the most significant biomechanical characteristics of lungs,
      reflecting the severity of the respiratory failure are the dynamic compliance,
      aerodynamic airway resistance, coefficient C20/C, and the time constant.
      Correlation between the index of oxygenation, clinical assessment of the severity
      of respiratory failure and the duration of control mechanical ventilation was
      demonstrated. CONCLUSION: Rate of hyperextension and time constant are expressed
      by the correlation with the level of the oxygenation index, which allows them to
      be used for screening evaluation of severity critically ill patients during
      admission to the neonatal intensive care unit.

PMID- 24749312
TI  - [Case of successful prevention of multiple organ dysfunctions in 74 years old
      patient with sepsis after Crawford surgery complicated with pleural empyema,
      chest wall tissues infection and osteomyelitis of ribs].
AB  - The article deals with a clinical case demonstrating that patient's elderly age
      is not an absolute contraindication for complex surgery in spite of high risk of
      postoperative complications. Early diagnostics, target treatment of the infection
      cite with vacuum-assisted therapy for wounds and the treatment of infectious
      complications based on individual characteristics of elderly patient with sepsis
      as an outcome of prosthetic thoracoabdominal aortic repair allowed avoiding
      multiple organ dysfunctions in the patient.

PMID- 24749313
TI  - [Outcomes of surgical correction of congenital tibia pseudarthrosis depending on
      the activation of HHV-6/HHV-7 viral infection in a child with neurofibromatosis
      type-1].
AB  - Neurofibromatosis type-1 (NF-1)--is a common genetic disease effecting the skin,
      subcutaneous tissue peripheral nerves and bones (tibia pseudarthrosis).
      Immunomodulatory viruses HHV-6 and HHV-7 are classifying as a genus of
      roseoloviruses of subfamily beta-herpesviruses. Reactivation of HHV-6 and HHV-7
      inhibits immune system and indirectly promote to other infectious agents. The
      article deals with a unique case repot of two repeated transplantations of fibula
      due to congenital tibia pseudarthrosis caused by NF-1. Results of the
      transplantations, related to active and latent HHV-6 and HHV-7 infection in a 6
      years old child are discussed in the paper.

PMID- 24749314
TI  - [Tactics of tracheal intubation in patient with tumor of the tongue base].
AB  - Anatomic deformations can cause complications during the tracheal intubation in
      the maxillofacial surgery and otorhinolaryngology. The article deals with a
      clinical case of tracheal intubation in a patient with the anatomic deformations.
      Successful tracheal intubation was performed in the patient in conditions of
      conscious and spontaneous breathing under the local anaesthesia, when a
      fibreoptic bronchoscopy was not available. Furthermore the article briefly
      discusses techniques of the tracheal intubation in conditions of anatomic
      deformations of the upper airways and methods of local anaesthesia for the guttur
      and hypopharynx.

PMID- 24749315
TI  - [Case report of successful treatment of the patient with stab wound of the neck
      complicated with massive blood loss and shock].
AB  - The article deals with a case report of successful treatment of patient with
      massive blood loss and shock. The observation showed that use of balanced
      crystalloid solution and modified gelatin 4% in the program of infusion therapy
      effectively corrects systemic haemodynamics and effect on haemostasis,
      electrolyte and acid-base balance.

PMID- 24749316
TI  - [Comparison of modern methods of respiratory oxygenation during double level
      tracheal resection and reconstruction (clinical report)].
AB  - The problem of respiratory support in tracheal surgery is still discussed in
      recent days. Anaesthesiologist must choose the most effective and safe
      respiratory technique during tracheal resection and reconstruction. The article
      deals with a case of comparison of apneic oxygenation (AO) and high frequency jet
      ventilation (HFJV) during double level tracheal resection and reconstruction in
      patient with multifocal tracheal stenosis and underlying cerebral trauma.
      MATERIALS AND METHODS: AO and HFJV were used due to surgical need for 20 min each
      technique. PvO2, PvCO2, hematocrit, blood glucose, acid-base balance in the v.
      Jugularis interna, noninvasive arterial pressure, heart rate, ECG and body
      temperature were fixed before and after the changing of respiratory support type.
      Additionally peak systolic speed (S) of blood flow in the a. Cerebralis media
      sinister was fixed by transcranial Doppler ("Angiodin BIOSS", Russia). RESULTS:
      Oxygenation of venous blood was sufficient after the both HFJV and AO use; PvO2
      was 67.6 and 74.3 torr respectively. Speed of PvCO2 increasing was higher during
      AO (1.46 torr per min) than during HFJV (0.73 torr per min). Increase of S was
      bigger during AO than HFJV as well (59 vs 37%). The changes of PvCO2 and S were
      normalized in 15 min after reconnection to conventional mechanical ventilation.
      Other fixed parameters were normal and same during the use of both respiratory
      techniques. The patient involved in the study did not have any neurological or
      surgical complications in early postoperative period. CONCLUSIONS: Both studied
      respiratory techniques provide sufficient blood oxygenation and can be
      accompanied with hypercapnia and cerebral hyperemia. These observations evident
      about the necessity to study the role of hyperoxia, hypercapnia and cerebral
      hyperemia in patients with underlying cerebral trauma undergoing tracheal
      resection and reconstruction. The study will help to make a strategy of the
      foreground use of HFJV and AO in these patients.

PMID- 24749317
TI  - [Application of desflurane in anaesthesiology].
AB  - Desflurane (Des)--is a modern inhalation anaesthetic available in Russia since
      August, 2013. Des is a halogenated ether; its chemical structure is 2
      difluoromethoxy-1-1-1-2-tetrafluoroethane (C3H2F6O). Special thermocompensated
      evaporators are used for Des dosing. Low solubility in blood and tissues of an
      organism causes fast absorption and elimination of Des. Blood/gas distribution
      ratio of Des is 0.42. Des distinctive properties are high saturated vapor
      pressure, super short duration of action and average power. Furthermore it is
      characterized by the minimal metabolism and lack of interaction with soda lime.
      Des is used for general anesthesia in a cardiac surgery neurosurgery, out-patient
      surgery, pediatric practice and other areas of surgery. Des has more positive
      qualities and fewer limitations, than other inhalation anaesthetics (halothane,
      isoflurane, sevoflurane). High cost of the anaesthetic is compensated by quality
      and controllability of anaesthesia and reduction of stay time in recovery unit.
      Fast elimination of the anaesthetic from a body allows reducing a frequency of
      complications connected with violation of upper airway and hypoxemia, promotes
      early discontinuation of artificial ventilation, reducing somnolence, earlier
      restoring a muscular tone in the postoperative period.

PMID- 24749318
TI  - [Iron metabolism and its role in traumatic disease].
AB  - The article reviews recent studies of iron exchange and its role in a traumatic
      disease and traumatic shock. The review stresses a relationship of iron
      metabolism disturbance with free radical oxidation, lipid peroxidation and
      multiple organ dysfunctions. The article deals with data of unbound iron collect
      mechanisms, ways of endotoxemia activation, haemostasis and haemodynamics
      disturbance proving the role of iron in a multiple organ dysfunctions during
      traumatic disease.

PMID- 24749319
TI  - [Neurovegetative stabilization as a pathogenetic therapy for brain damage].
AB  - The article deals with neurovegetative stabilization as a pathogenetic therapy
      for brain damage. The approach is based on hypothesis that pharmacological
      effecting on central nervous system is able to make a passive protective medical
      system which can be close to passive protective systems widely represented in the
      nature. Complex opioid and clonidine administration provides sufficient level of
      neurovegetative stability on account of effecting on neuro-regulative structures
      the brain steam. Neurovegetative stabilization should be carry out in order of
      warning principle. In our opinion optimal doses are fentanyl 0.2-1.4 mkg kg(-1)
      per hour, clonidine 0.2-0.7 mkg kg(-1) per hour, propofol 0.5-2 mkg kg(-1) per
      hour, penthonal sodium 1-4 mkg kg(-1) per hour; diazepam 0.4-0.5 mkg kg(-1), and
      midazolam 0.05-0.2 mkg kg(-1) per hour. A criterion of the therapy sufficiency is
      a consistency between changes of different functional parameters. We believe the
      most important that new level of functioning must be maximally integrated and
      harmonized. It is possible if all pharmacological agents include the most
      reliable programs of adaptation complex human body reactions.

PMID- 24749320
TI  - [Intracranial arterio-venous malformations during pregnancy, labor and
      postpartum].

PMID- 24749321
TI  - [Wobbling of surgical education due to the current vogue of endoscopic surgery].

PMID- 24749322
TI  - [No-fault compensation system].

PMID- 24749323
TI  - [Mid- and long-term outcome of endovascular repair in patients with aortic
      aneurysm].

PMID- 24749324
TI  - [Present status of stent-graft aortic aneurysm repair in Japan].
AB  - An industrially produced stent graft for abdominal aortic aneurysm repair was
      first approved in Japan in July 2006, followed by a device for thoracic aortic
      aneurysm repair the next year. After seven years, most descending thoracic aortic
      aneurysms and about half of abdominal aortic aneurysms are treated with four
      types of device each. In 2012, the number of patients who underwent endovascular
      aneurysm repair (EVAR) and thoracic endovascular aortic repair (TEVAR), of
      facilities performing those procedures per 1 million population, and of EVAR and
      TEVAR patients per facility was 7,600 and 3,700, 3.8 and 3.0, and 18.4 and 12.3,
      respectively. The incidence of type I endoleak and rate of hospital death was
      1.1% and 0.6%, respectively, in 3,124 cases of EVAR performed during the initial
      2.5 years. A 6.6% rate of type I endoleak and 2.7% hospital death rate were
      observed during the first 2 years of TEVAR. The satisfactory curative effects of
      EVAR and TEVAR are confirmed by these follow-up data.

PMID- 24749325
TI  - [Mid- and long-term outcome of endovascular aneurysm repair in patients with
      abdominal aortic aneurysm].
AB  - In Japan, endovascular aneurysm repair (EVAR) came into use later than in the
      USA. The Zenith AAA endovascular graft finally received regulatory approval in
      July 2006. Now, four systems, the Zenith, the Excluder, the Powerlink system, and
      Endurant stent graft have been approved for insurance reimbursement. The
      advantages of EVAR are that is a less-invasive procedure, involves little blood
      loss, and requires only a short time in surgery and short hospital stay. EVAR is
      indicated for older patients and those in poor general condition. On the other
      hand, the disadvantages of EVAR are anatomic restrictions and a higher
      reintervention rate than that after open surgery. Therefore, careful follow-up is
      required. The mid- and long-term results following the introduction of stent
      grafts in Japan are generally good compared with the outcome data reported in the
      European and US literature. The stent graft procedure spread safely following the
      introduction of new medical materials. Several studies showed the benefit of EVAR
      in reducing procedure-related mortality and morbidity rates after open aneurysm
      repair. The current good results of EVAR have shifted the choice toward the
      endovascular option. With the development of new devices and skillful techniques,
      the indications for EVAR will broaden. This review reports the mid- and long-term
      outcomes of EVAR and reviews the literature.

PMID- 24749326
TI  - [Mid- and long-term results of thoracic endovascular aortic repair for thoracic
      aortic pathologies].
AB  - Thoracic endovascular aortic repair (TEVAR) for thoracic aortic pathologies has
      become common worldwide as a less-invasive alternative to open surgery, and
      satisfactory early outcomes were achieved. However, there have been few reports
      of mid- and long-term results in this field. In this study, we reviewed the mid-
      and long-term results of the TEVAR procedure for the treatment of thoracic aortic
      pathologies. In coming years, there will be intense competition to develop the
      devices themselves (e.g., branched devices), improve delivery systems, and
      supplement devices with auxiliary functions. There are high expectations for
      those next-generation devices and how they will improve and advance treatment
      methods. Cardiovascular surgeons look forward to the future of hybrid surgery 5
      years from now.

PMID- 24749327
TI  - [Current status of total endovascular treatment for thoracoabdominal aortic
      aneurysms].
AB  - The repair of thoracoabdominal aortic aneurysms (TAAAs) represents a considerable
      technical challenge. Open repair of TAAAs has been considered the gold standard.
      Despite improvements in surgical techniques, spinal cord protection, and
      postoperative critical care support, patients who undergo open repair are faced
      with a high mortality rate. Spinal cord ischemia is a well-known complication in
      the treatment of TAAAs. Cerebrospinal fluid drainage (CSFD) may increase the
      perfusion pressure to the spinal cord and hence reduce the risk of ischemic
      spinal cord injury. Open repair is performed in a standard procedure using a
      partial corporeal perfusion system, often with the use of CSFD. Endovascular
      repair procedures include the use of tailor-made branched endografts, customized
      fenestrated/branched endografts (Cook, Inc.), endografts with visceral artery
      coverage, and abdominal debranching with endografting. Stent-graft repair is one
      of the few treatment options in patients determined to be ineligible for surgery.
      The use of open repair for good-risk patients and selection of the
      fenestrated/branched endograft procedure for high-risk patients appear to lead to
      improved overall outcomes in the treatment of TAAAs. We report our experience in
      total endovascular treatment of TAAAs.

PMID- 24749328
TI  - [Diagnosis and treatment of endoleak after thoracic endovascular aortic repair or
      endovascular aortic repair].
AB  - Endoleak is a common complication after thoracic endovascular aortic repair
      (TEVAR) or endovascular aortic repair (EVAR), occurring in up to 30% of cases,
      and therefore lifelong imaging surveillance is important. Endoleak is defined as
      the persistence of blood flow outside the lumen of the stent graft, but within
      the aneurysm, which can be classified into five categories. Typical features of
      the different types of endoleak are discussed as well as the imaging modalities
      to detect and classify an endoleak and the endovascular treatment options.
      Multidetector computed tomography angiography is the most widely used technique
      for the detection of endoleaks after TEVAR and EVAR. Type I and III endoleaks
      require immediate treatment because they are prone to rupture. Treatment is
      restricted to type II endoleaks with enlargement of the aneurysm sac > 5mm over a
      6-month period or > 10mm in comparison with the diameter before treatment. The
      concept of the intervention should be to embolize the inflow and outflow vessels
      and the communicating channels in between, mainly using glue. Treatment of type V
      endoleaks (endotension) remains unclear and may be conservative, endovascular
      (placing a new stent graft), or surgical.

PMID- 24749329
TI  - [Future outlook for endovascular aneurysm repair].
AB  - The future design of endovascular aneurysm repair depends on the development of
      device systems. In device development, however, there are some differences
      between the focus of manufacturing units and clinical requirements, i.e., the
      main targets of device manufacturers are the development of branched or
      fenestrated devices and low-profile systems, while clinical practice requires a
      better fit between the aortic wall and devices, improved device durability, and
      solutions for troublesome complications (type I endoleak, etc.) over the long
      term. The results of endovascular aneurysm repair (EVAR) and thoracic
      endovascular aortic repair (TEVAR) will improve with the incorporation of
      clinical needs into device development. EVAR and TEVAR will play a leading role
      in aneurysm repair in the near future.

PMID- 24749330
TI  - [Clinical practice in genetic diagnosis of familial tumors].

PMID- 24749331
TI  - [What we can learn from a case of medical malpractice--the president of the
      university hospital was accused of violating the Occupational Safety and Health
      Act for not instructing the technician to when performing an endoscopy].

PMID- 24749332
TI  - [Laparoscopy and endoscopy cooperative surgery (LECS) for gastric submucosal
      tumor].

PMID- 24749333
TI  - [The role of specific nurses in general surgery].

PMID- 24749335
TI  - [Experience of 2013 Japan Exchange Fellow of the Japan Surgical Society and the
      American College of Surgeons].

PMID- 24749334
TI  - [Chronic surplus of Japanese cardiac surgeon--ideal nurse practitioner for
      cardiac surgery, cardiac surgeon's attitude toward the future].
AB  - It is chronically surplus of doctors in the world of cardiac surgery. There are
      too many cardiac surgeons because cardiac surgery requires a large amount of
      manpower resources to provide adequate medical services. Many Japanese cardiac
      surgeons do not have enough opportunity to perform cardiac surgery operations,
      and many Japanese cardiac surgery residents do not have enough opportunity to
      learn cardiac surgery operations. There are physician assistants and nurse
      practitioners in the US. Because they provide a part of medical care to cardiac
      surgery patients, American cardiac surgeons can focus more energy on operative
      procedures. Introduction of cardiac surgery specialized nurse practitioner is
      essential to deliver a high quality medical service as well as to solve chronic
      problems that Japanese cardiac surgery has had for a long time.

PMID- 24749336
TI  - [The bio-effects of high single-dose radiation on xenografts of Lewis lung
      carcinoma].
AB  - OBJECTIVE: To investigate the bio-effects of high single-dose radiation on
      xenografts of Lewis lung carcinoma. METHODS: Female 8-week-old C57 mice bearing 4
      6 mm diameter Lewis lung carcinoma tumors in the hind legs were divided into 3
      groups, control group (0 Gy), high single-dose group (12 Gy/one fraction/day) and
      routine radiation group (22 Gy/11 fraction/15 d). The mean biological effective
      dose (BED) of both radiation groups was 26.4 Gy. Changes in hypoxia, DNA damage
      and cell cycle of the tumor cells at 1, 3, 8, 15 and 21 d after first irradiation
      was assessed by immunofluorescence and flow-cytometry and the tumor growth curve
      was also made. RESULTS: Compared to the fractionated treatment, the tumor growth
      was delayed after single dose irradiation. The percent of hypoxic cells after
      single dose radiation was lower than fractioned irradiation at 3, 8, 15 d after
      first radiation. The foci of gamma-H2AX showed that the single dose caused
      heavier DNA damages than fractioned irradiation at 1, 3 d after first radiation.
      The decline of G0/G1 percentage and increase of G2/M percentage of cells was
      found in both radiation schedules, but the G2/M percentage after single dose
      radiation was higher. CONCLUSION: In the C57 mice bearing Lewis lung carcinoma,
      the high single-dose regimen inhibits the tumor growth more than fractioned
      irradiation. We hypothesized that conversion of high single-dose to BED using the
      LQ formalism under estimated the in vivo effect of hypofractionated radiation.

PMID- 24749337
TI  - [DNA damage response of epithelial ovarian cancer cells (primary culture) to
      chemo-radiotherapy].
AB  - OBJECTIVE: To detect protein dynamic changes of cellular localization and the DNA
      damage response of epithelial ovarian cancer cells to chemo-radiotherapy.
      METHODS: 28 specimens of epithelial ovarian cancer were collected, with 6 cases
      diagnosed as borderline serous cystadenoma, 5 as highly differentiated, 6 as
      medium differentiated and 11 as poorly differentiated cystadenocarcinoma.
      Collagenase A was used for digesting tissues before primary culture. We compared
      the characteristics of cells cultured in different mediums (MCDB/M199 medium,
      primary culture medium, and DMEM medium) supplemented with multiple growth
      promoting factors. The characteristics of cells were examined in terms of the
      maintenance of normal cell morphology, proliferation potential, and cell fibrosis
      proteins (53BP1 and gamma-H2AX) responsive to DNA damage [those in the ATM
      checkpoint pathway determined by indirect immunofluorescent staining after
      treatment with camptothecin (CPT) and X-ray]. RESULTS: Normal morphology was
      maintained relatively well in the cells cultured in MCDB/M199 medium and its cell
      fibrosis was slow compared with the cells cultured in other media. Gradually
      increased endogenous damage was demonstrated by the expression of 53BP1 and gamma
      H2AX foci (P < 0.05) in all of the ovarian primary cells. After treatment with
      CPT and ionizing radiation, increased levels of DNA double-strand breaks were
      observed indicating a classic DNA damage response. CONCLUSION: We have
      successfully established a protocol for the primary culture of epithelial ovarian
      cancer cells, which provides an important platform for characterizing DNA damage
      responses of the cells. With the progression of epithelial ovarian cancers, the
      ATM checkpoint pathway is activated by endogenous DNA lesions. This signaling
      pathway can be further activated by CPT or X-ray irradiation, hampering the
      growth of tumor cells and further progression of cancers.

PMID- 24749338
TI  - [Differentiation of human bone marrow mesenchymal stem cells into Leydig or
      steroidogenic cells in vivo].
AB  - OBJECTIVE: To study the differentiation of human bone marrow mesenchymal stem
      cells (BMSCs) into Leydig or steroidogenic cells in vivo and the immunoreaction
      related to transplantation into mouse testis. METHODS: After differentiation and
      cultivation, the 3rd-passage BMSCs were collected and labeled with Hoechest
      33342, and joined the saline fluorouracil to form cell-suspending fluid. After
      injection of the etgane dimethane sulphonate (EDS), the mice received the
      transplanted cell-suspending fluid by testis net injection with a dose of each
      side testicular 0.05 mL. Since the first day prior to transplantation, mice were
      executed every 2 d (one mouse each time) and the testosterone concentrations were
      analyzed. The control group included 20 BALB/c mice without any treatment during
      the same period. The results were analyzed by microscopic observation, using
      3beta-hydroxysteroid dehydrogenase (3beta-HSD) monoclonal antibody and mouse anti
      human cell nucleus monoclonal antibody for immunofluorescence assay on the
      testis. For tracking the BMSCs, the cells which were positively stained with both
      3beta-HSD and mouse anti-human cell nucleus monoclonal antibodies were retrieved.
      RESULTS: Certain killing effect of EDS to the mouse Leydig cells was observed.
      Transplantation of human BMSCs into the mouse testis by testis net injection was
      effective and feasible, no immunoreactions were detected. After transplantation,
      no positive cells of 3beta-HSD) and mouse anti-human cell nucleus monoclonal
      antibody were found. CONCLUSION: Transplantation of human BMSCs into the mouse
      testis by testis net injection was effective and feasible, no immunoreactions
      were detected. After transplantation, the human BMSCs failed to differentiate
      into Leydig cells or steroidogenic cells.

PMID- 24749339
TI  - [Effects of CTCF on human liver cancer stem cells and cell proliferation].
AB  - OBJECTIVE: To explore the effects of CCCTC-binding factor (CTCF) on human liver
      cancer stem cells (HepG2) and cell proliferation of HepG2 and Nasopharyngeal
      carcinoma cell line (CNE1). METHODS: The pEGFP-N1/CTCF, CTCF-shRNA and GFP-shRNA
      plasmids were constructed and transfected into HepG2 and CNE1 cells, and RT-PCR
      or Western blot were performed to detect the mRNA or protein levels of CTCF. The
      subpopulation of CD90+ cancer stem cells in HepG2 cells transfected with CTCF
      shRNA plasmid or GFP-shRNA plasmid (as transfection control) were assayed by flow
      cytometry with the wild type HepG2 cells as control. Proliferation of cells
      transfected with CTCF-overexpression or CTCF-shRNA plasmid was evaluated by MTT
      assay. RESULTS: The levels of both mRNA and protein of CTCF were increased in
      pEGFP-N1/CTCF transfected HepG2 and CNE1 cells compared to that in pEGFP-N1
      transfected cells (P < 0.05), and decreased in CTCF-shRNA transfected cells
      compared to that in cells transfected with GFP-shRNA (P < 0.05). The results of
      flow cytometry demonstrated that, detection rate of CD90+ cells in cells
      transfected with CTCF-shRNA plasmid [(1.7330 +/- 0.4177)%] was obviously higher
      than that of wild-type HepG2 cells [(0.5750 +/- 0.0629)%] and cells transfected
      with GFP-shRNA plasmid [(0.3500 +/- 0.0866)%] (P < 0.05). The results of MTT
      analysis showed that, alteration of CTCF had no effect on cancer cell
      proliferation (P > 0.05). CONCLUSION: CTCF inhibits human liver cancer stem cells
      but no effect on cell proliferation.

PMID- 24749340
TI  - [Effects of p66shc adapter protein and estrogen on cardiomyocyte apoptosis
      induced by angiotensin II].
AB  - OBJECTIVE: To explore the role of p66shc in cardiomyocyte apoptosis induced by
      angiotensin (Ang) II and the effect of estrogen pretreatment. METHODS: Neonatal
      rat cardiomyocytes were randomly divided into five groups: normal control, 10(
      11) mol/L Ang II, 10(-9) mol/L Ang II, 10(-7) mol/L Ang II, and 10(-7) mol/L Ang
      II + estrogen treated groups. The cell viability was measured by MTT. The level
      of reactive oxygen species (ROS) and cell apoptosis rate were measured by flow
      cytometry. Mitochondrial membrane potential (MMP) was detected using a
      fluorescence microplate reader, and the protein expression of phosphorylated and
      total p66shc were detected using Western blot. RESULTS: With the increase of Ang
      II concentrations, cell viabilities and MMP levels decreased, whereas, the levels
      of ROS and cell apoptosis rates increased (P < 0.05). Pretreatment with estrogen
      significantly attenuated the cardiomyocyte injury induced by Ang II (P < 0.05).
      The protein expression of phosphorylated p66shc in the whole cell lysates and
      total p66shc in the mitochondria increased in a dose-dependent manner when
      cardiomyocytes were exposed to Ang II (P < 0.05). Pretreatment with estrogen
      significantly down-regulated the protein expression of phosphorylated p66shc in
      the whole cell lysates and total p66shc in the mitochondria (P < 0.05).
      CONCLUSION: p66shc is involved in cardiomyocyte apoptosis induced by Ang II, and
      estrogen could attenuate Ang II induced cardiomyocyte injury through down
      regulating the protein expression of p66shc.

PMID- 24749341
TI  - [Effect of Qufeng Tongluo Recipe on the expressions of connexin 36 protein and
      gene in rat mesangial cells].
AB  - OBJECTIVE: To determine the effect of Qufeng Tongluo Recipe (QFTLR) on the
      expressions of connexin 36 (Cx36) protein and gene in rat mesangial cells (MCs)
      and the proliferation of the MCs. METHODS: Serum samples containing Benazepril
      (Bena) and QFTLR were prepared in line with serum pharmacology methodology. The
      MCs cultured in vitro were divided into normal control and Lipopolysaccharide
      (LPS), Bena and QFTLR treated groups. The expressions of Cx36 protein and gene
      were detected by laser scanning confocal microscope (LSCM), Western blot,
      immunohistochemical assay and quantitative real time polymerase chain reaction
      (QRT-PCR) respectively. RESULTS: Compared with the control, higher level of Cx36
      protein expression was found in the MCs than treated with LPS (P < 0.01). Both
      Bena and QFTLR lowered the level of Cx36 protein expression in the MCs treated
      with LPS significantly (P < 0.01 or P < 0.05). Similar results were found with
      the expression of Cx36 mRNA. CONCLUSION: QFTLR inhibits the proliferation of rat
      MCs, possibly through down-regulating the expressions of Cx36 protein and gene.

PMID- 24749342
TI  - [Expression of heparanase in kidney of rats with respiratory syncytial virus
      nephropathy and its relationship with proteinurina].
AB  - OBJECTIVE: To explore the role of heparanase in the pathogenesis of respiratory
      syncytial virus (RSV) nephropathy in rats model. METHODS: Twenty 150-200 g
      Sprague-Dawley (SD) rats (n = 5 per group) were inoculated with 6 x 10(6) PFU RSV
      and sacrificed on days 4, 8, 14 and 28 postinoculation (RSV4, RSV8, RSV14 and
      RSV29). Five SD rats inoculated with Dulbecco's minimum essential medium were
      served as normal control. The expression levels of heparanase protein and mRNA in
      the rat renal tissue of each group were determined by immunohistochemical
      staining and real-time quantitative RT-PCR respectively. The proteinurina was
      also measured and then the relationship between the expression level of
      heparanase and the 24-hour urinary protein was studied. RESULTS: The rats with
      RSV nephropathy exhibited higher proteinuria in comparison with normal rats, and
      the 24-hour urinary protein level was significantly different between each RSV
      nephropathy group (RSV14 > RSV8 > RSV28 > RSV4, P < 0.05). Compared with normal
      control, the rats with RSV nephropathy showed up-regulated expression of
      heparanase protein in glomeruli. The expression levels of heparanase protein in
      RSV8 and RSV14 group were higher than those in RSV4 and RSV28 group (P < 0.05).
      There was a linear positive correlation between the expression level of
      glomerular heparanase protein and the quantity of 24-hour urinary protein (r =
      0.783, P < 0.05). Compared with normal control group, the expression levels of
      heparanase mRNA in the kidney from RSV4, RSV8, RSV14, and RSV28 group were
      elevated (RSV14 > RSV8 > RSV4 > RSV28 , P < 0.05). There was a linear positive
      correlation between the expression level of renal heparanase mRNA and the
      quantity of 24-hour urinary protein (r = 0.725, P < 0.05). CONCLUSION: The
      increased expression of heparanase in kidney may be important to the loss of
      glomerular negative charge in glomerular basement membrane which is involved in
      the pathogenesis of RSV nephropathy in rats.

PMID- 24749343
TI  - [Protective effect of ischemia preconditioning of lower limbs on brain ischemia
      reperfusion injury via neural pathways].
AB  - OBJECTIVE To explore if ischemia preconditioning of lower limbs could protect the
      local ischemia reperfusion damage in rat brain and the role of neural pathways
      during the process. METHODS: Fifty male Sprague-Dawley rats were randomly
      assigned into five groups (n = 10 for each group). Group I was sham group. Group
      II was the occlusion of middle cerebral artery (MCAO) for 90 min. Group III was
      remote ischemic preconditioning (RIPC) 24 h before MCAO. Group IY was femoral
      nerve and sciatic nerve (FS) resected before RIPC and MCAO. Group V was FS
      resected only before MCAO. All the rats in the later four groups were subjected
      to brain reperfusion after MCAO for 90 min. The brain samples were harvested 24 h
      after MCAO for the evaluation of neuroligical deficit score (NDS) and infarct
      volume, histomorphlogical study with HE staining, as well as the evaluation of
      neuron apoptosis with TUNEL staining and Caspase-3 staining. RESULTS: The infarct
      volume in group RIPC + MCAO (18.24%) was smaller than that in MCAO group
      (30.92%), and TUNEL and Caspase-3 staining also demonstrated significantly lesser
      apoptotic neurons (20.81, 5.78) in comparison with MCAO group (45.23, 12.94).
      However, the infarct volume (28.77%) and apoptotic neurons (53, 11.83) of FS +
      RIPC + MCAO group did not show statistical difference when compared with those of
      MCAO group. The results of NDS and HE staining in RIPC + MCAO group were better
      than those in MCAO group, while they showed no statistical difference in the
      condition of nerve resected before RIPC + MCAO when compared with MCAO group.
      CONCLUSION: The ischemia preconditioning of lower limbs may provide protection on
      ischemia-reperfusion injury in rats brain through neural pathways.

PMID- 24749344
TI  - [Alteration of apoptosis and Akt/mTOR signal pathway in hippocampal neurons of
      rat with post-traumatic stress].
AB  - OBJECTIVE: To observe the changes of apoptosis and protein kinase B/the mammalian
      target of Rapamycin (Akt/mTOR) signal pathway in hippocampal neurons of rat with
      post-straumatic stress disorder (PTSD), and to investigate the mechanism of PTSD.
      METHODS: Sixty male adult SD rats were divided into control group (n = 10) and
      PTSD (n = 50) model group. The PTSD animal model was established by giving the
      rats single-prolonged stress followed a single inescapable electric foot shock
      (SPS & S). The neuronal apoptosis of hiappocampus of PTSD rats at 1 d, 4 d, 7 d,
      14 d and 28 d after model established was detected by flow cytometry (FCM). The
      expressions of phosphatase and tensin homology deleted on chromosome Ten (PTEN),
      phosphorylation of ARt and mTOR (p-Akt and p-mTOR) protein were detected by
      Western blotting. RESULTS: The apoptotic cell rate in PTSD 1 d, 4 d, 7 d and 14 d
      rats were higher than that in control rats (P < 0.05). The PTEN expression level
      was higher since PTSD 1 d than that in control group, and peaked in PTSD 4 d (P <
      0.05). The p-Akt expression level was lower in PTSD 1 d than that in control
      group, and then increased in various time points after PTSD, but it was still
      lower in PTSD 28 d (P < 0.05). The p-mTOR expression level was lower than that in
      control group since PTSD 4 d, and then increased in various time points after
      PTSD 4 d, but it was still lower in PTSD 28 d (P < 0.05). CONCLUSION: The
      Akt/mTOR signal pathway was actived in hippocampal neurons of PTSD rats, and
      which was involved in neuronal apoptosis regulation.

PMID- 24749345
TI  - [Effect of curcumin on bronchopulmonary dysplasia induced by 600 ml/L oxygen in
      neonatal rats].
AB  - OBJECTIVE: To investigate the protective effects and potential mechanism of
      curcumin on bronchopulmonary dysplasis (BPD) induced by 600 mL/L oxygen in
      newborn rats. METHODS: 108 Sprague-Dawley (SD) specific pathogen-free newborn
      rats within 6 h after birth were randomly divided into room air group (RA group),
      600 mL/L oxygen group (O2 group) and 600 mL/L oxygen + Curcumin group (O2 + Cu
      group). Eight rats were randomly taken from each group and killed at 4, 7 and 14
      d, respectively, after the treatment, and their lung tissues were incised for HE
      staining. The expressions of IL-6, IL-10 in serum and lung tissue were detected
      by ELISA; and the protein expression of IGF-I was measured by immunohistochemical
      method. RESULTS Comparing with the RA group, we found that newborn rats exposed
      to 600 mL/L oxygen develop a heterogeneous parenchymal lung injury with areas of
      arrested alveolarization and growth mixed with areas of interstitial thinning,
      meanwhile, both the expression of IL-6 and IL-10 in serum and lung tissue
      increased significantly (P < 0.05). However, in O2 + Cu group, IL-6 expression
      was decreased in different degrees while IL-10 increased significantly (P <
      0.05). The highest expression level of IGF-I in RA group were much higher from 4
      d to 7 d (alveolar development period) but significantly lower in 14 d. There was
      a positive correlation between IGF-I and alveolar development. In comparison with
      RA group, the expression levels of IGF-I in O2 group were significantly lower in
      4 d and 7 d but were significantly higher in 14 d (P < 0.05); In comparison with
      O2 group, the expression levels of IGF-I in O2 group significantly increased in 4
      d and 7 d but significantly reduced in 14 d (P < 0.05). CONCLUSION: Curcumin may
      partly prevent the lung injury induced by prolonged hyperoxia exposure in
      neonatal rats probably via modulating the expressions of IL-6, IL-10 and IGF-I in
      serum and lung tissue.

PMID- 24749346
TI  - [Endothelial protection of tanshinone in rats of severe acute pancreatitis].
AB  - OBJECTIVE: To investigate the protective effection of tanshinone on endothelial
      cells of severe acute pancreatitis (SAP) rats and the effection of tanshinone on
      apoptosis of aorta endothelium. METHODS: Using 8% L-arginine intraperitoneal to
      inject in rats, 4.4 mg/g per time, repeat injection 1 hour later, for
      establishing SAP model. Model rats were randomly divided into SAP group and
      tanshinone group. 20 mg/kg Sodium Tanshinon II Asilate i. p. was applied to
      tanshinone group,while the saline was used to replace Sodium Tanshinon II Asilate
      in SAP group. Twelve rats of each group were sacrificed at 12 h, 24 h after
      treatment. The pathological changes in pancreatic tissues were observed.
      Abdominal aorta samples were collected for terminal deoxynucleotidyl transferase
      mediated dUTP biotin nick end labelling (TUNEL) and reverse transcription PCR (RT
      PCR) tests. The blood samples were collected from abdominal aorta for analysis.
      Detections: (1) The concentration of Von Willebrand factor (vWF), soluble
      endothelial protein C receptor (sEPCR), tumor necrosis factor alpha (TNF-alpha)
      and the serum levels of nitric oxide (NO) were quantitative messured by ELISA.
      (2) The apoptosis of aorta endothelium cell was examined using TUNEL method. (3)
      Bcl-2 and Bax mRNA expression were measured by RT-PCR. RESULTS: The pathological
      changes of pancreatic tissues were more severe in SAP group than those in
      tanshinone group. Compared with SAP group, treatment with tanshinone effectively
      inhibited TNF-alpha (P < 0.05), vWF (P < 0.05) and sEPCR (P < 0.05) expression
      and depressed apoptosis of aorta endothelium cell, increased the expression of
      Bcl-2 mRNA (P < 0.05), Bcl-2 mRNA/Bar mRNA ratio (P < 0.05) and the expression of
      Bax mRNA (P < 0.05) were decreased significantly. CONCLUSION: Sodium Tanshinon II
      Asilate can lighten the SAP rats aortic endothelial injury and apoptosis of
      endothelial cells can reduce endothelial damage of SAP rats by TNF-alpha
      expression suppression.

PMID- 24749347
TI  - [Major hypoglycemic ingredients of Panax notoginseng saponins for treating
      diabetes].
AB  - OBJECTIVE: To explore the mechanism of Panax notoginseng saponins (PNS) on
      diabetes treatment and mass loss in KK-Ay mice with genetic type 2 diabetes
      mellitus (DM), and to identify the main hypoglycemic ingredients. METHODS: C57
      and KK-Ay DM mice were divided into eight groups each comprising six mice:
      healthy normal, DM model, and DM model treated with PNS (200 mg/kg body mass),
      ginsenoside Re (Re, 14 mg/kg body mass), ginsenoside Rd (Rd, 15 mg/kg body mass),
      ginsenoside Rgl (Rg1, 40 mg/kg body mass), ginsenoside Rb1 (Rb1, 60 mg/kg body
      mass) and notoginsenoside R1 (R1, 6 mg/kg body mass). The PNS were
      intraperitoneal injection administered for 30 d, while the Re, RB1, Rg1, Rd and
      Re were intraperitoneal injection administered for 12 d. The fasting blood sugar
      (FBG), glucose tolerance (GT), serum insulin, leptin, body weight, food
      consumption, and levels of adipose tissue and blood lipid were determined.
      RESULTS: On 12 d, lower FBG levels were found in the PNS and Rb1 treated mice
      compared with the model mice (P < 0.05). No statistical differences in FBG levels
      were found between the rest of the treatment groups and the model group (P >
      0.05). After 30 d continuous administration of PNS, the FBG level of the mice
      further declined (P < 0.01). Meanwhile, the serum insulin (P < 0.05) and insulin
      resistance index (P < 0.01) of the PNS treated mice also declined significantly.
      Compared with model group, the PNS group had lower levels of body weight growth,
      food consumption, adipose tissue, and leptin (P < 0.05). Lower FBG level was also
      found in Rb1 treated mice (12 d of administration), P < 0.05. CONCLUSION: PNS has
      anti-hyperglycemic and anti-obesity activities by improving insulin and leptin
      sensitivities in KK-Ay mice. Rb1 may be the hypoglycemic ingredient in the PNS
      extract.

PMID- 24749348
TI  - [The influence of fibronectin on the formation of multi-cellular spheroid of
      ovarian cancer].
AB  - OBJECTIVE: To investigate the role of Fibronectin in the formation of multi
      cellular spheroid of ovarian cancer and the integrin receptor involved in the
      process. METHODS: In vitro model of multi-cellular spheroid of SKOV3 was
      constructed by liguid overlay technique. The influence of fibronectin on the
      formation of the spheroid was observed. The gene expressions of potential
      integrin receptors were examined from the levels of mRNA and protein using real
      time reverse transcription PCR and Western-blot. RESULTS: Fibronctin stimulated
      the formation of multi-cellular spheroid of ovarian cancer larger than 250
      microm. fibronectin suppressed the expression of subtype of integrin receptor
      ITGA5. CONCLUSION: Fibronectin can enhance the formation of multi-cellular
      spheroid of ovarian cancer. The subtype of integrin receptor ITGA5 is probably
      involved in the process.

PMID- 24749349
TI  - [Influence of capsaicin sensitive C fibers denervation on lung ischemia
      reperfusion injury].
AB  - OBJECTIVE: To investigate the role of Capsaicin sensitive C fibers (CapsCF)
      denervation in lung ischemia-reperfusion (IR) injury and the possible mechanism
      related to oxidative stress. METHODS: Thirty two male New Zealand rabbits were
      randomized into four groups: IR group (IR), sham group (S), capsaicin pretreated
      IR group (CIR), and capsaicin pretreated sham group (CS). The rabbits in CIR and
      CS groups were pretreated with capsaicin (100 mg/kg) to induce functional
      ablation of CapsCF, and then subjected to lung ischemia and reperfusion. The
      rabbits in IR group were not treated with capsaicin before lung ischemia and
      reperfusion. Thereafter, blood samples and lung tissue samples were obtained for
      blood gas and biochemical analyses, including the measurements of malondialdehyde
      (MDA), superoxide dismutase (SOD), catalase (CAT). The lung wet/dry weight ratio
      and histopathological changes were also assessed. RESULTS: Compared to S and CS
      group, partial pressure of oxygen (PO2) values in IR and CIR groups significantly
      decreased (P < 0.05). In contrast, the alveolar-arterial oxygen gradient (A
      aDO2), lung wet/dry weight ratio increased in IR and CIR groups (P < 0.05).
      Capsaicin pretreatment in CIR group increased lung wet/dry weight ratio and lung
      pathologic lesions, along with higher level of MDA and lower activity of SOD and
      CAT (P < 0.05, vs. IR). CONCLUSION: Denervation of CapsCF aggravated lung
      ischemia-reperfusion injury of rabbits, which seems to be closely related to the
      excerbation of oxidative stress.

PMID- 24749350
TI  - [Expression and clinical significance of bone morphogenetic protein 6 in human
      breast cancer].
AB  - OBJECTIVE: To investigate the expression pattern and clinical significance of
      bone morphogenetic protein 6 (BMP6) in breast tissues. METHODS: The tumor and
      adjacent noncancerous tissues were harvested from 36 cases of breast cancer, the
      expression level of BMP6 mRNA of each sample was measured by quantitative RT-PCR.
      Immunohistochemistry study was used to examine BMP6 protein expression in 80
      cases of breast cancer, then the relationship between the expression of BMP6 and
      relevant clinical and pathological parameters was analyzed. RESULTS: BMP6 mRNA
      expression in breast cancer was significantly reduced when compared with normal
      breast tissues (P< 0.01), BMP6 mRNA level in estrogen receptor-positive (ER)
      breast cancer was distinctly higher than that in ER breast cancer. The expression
      of BMP6 mRNA was correlated to tumor grade (P < 0.01). The expression level of
      BMP6 protein in breast cancer was associated to ER and PR status, histological
      grade and Ki-67 status (P < 0.05), but not correlated to age, tumor size, human
      epidermal factor receptor 2 (Her2) status and molecular subtypes of breast cancer
      (P > 0.05). CONCLUSION: The ectopic expression of BMP6 may play an important role
      in the development and progression of breast cancer.

PMID- 24749351
TI  - [Sequence analysis of G glycoprotein gene of human respiratory syncytial virus].
AB  - OBJECTIVE: To understand the variation of G glycoprotein gene of human
      respiratory syncytial virus (HRSV) obtained from Sichuan in 2010 and determine
      the dominant genotypes. METHODS: G glycoprotein gene of seven cases of subtype A
      and eleven cases of subtype B of HRSV were amplified by RT-PCR and sequenced. The
      phylogenetic trees were constructed to determine the subtype of samples. And
      then, the genetic variations of the second hypervariable region of G glycoprotein
      gene were studied. RESULTS: The nucleotide genetic distances of G glycoprotein
      gene in subtype A and subtype B HRSV were 0.022 +/- 0.005 and 0.073 +/- 0.010,
      respectively. Transitions were more prevalent than transversions, GA -AG were the
      most frequent transitions detected among group A viruses, while UC+CU transitions
      were the most among group B. Phylogenetic analyses demonstrated that 7 subtype A
      virus could be clustered into one genotype, genotype GA2, and 11 subtype B virus
      could be clustered into two genotypes, GB2 and BA. The length of G protein gene
      in group A was all 298aa, but in group B included 295aa, 312aa and 315aa.
      Selective pressure was purifying selection in both subtypes. 9 positively
      selected sites in group A and 1 in group B on the second hypervariable region of
      G protein were identified. CONCLUSION: GA2, GB2 and BA were the main genotype.
      The changes may favor virus escape from the host immune response including the
      variation of the G protein gene length, frequency of nucleotide changes and
      selective pressure.

PMID- 24749352
TI  - [Study on the relationship between the MTHFR polymorphism, the level of the folic
      acid and the cervical cancer susceptibility].
AB  - OBJECTIVE: To study the relationship between the occurrence of the uterine cervix
      cancer and the risk factors, such as the methylene tetrahydrofolate reductase
      (MTHFR) 1298 polymorphism, the level of the folic acid and so on. METHODS: The
      cases from some hospitals, including the Xiamen No. 1 Hospital, the Xiamen
      Maternal and Child Health Hospital and the Xiamen Traditional Chinese Medical
      Hospital during the year 2007 to 2011 were selected and divided into two groups,
      one was the cancer group with 129 cases of the cervical cancer, and the other was
      the control group with 214 non-cervical-cancer women. Through using the
      questionnaires and testing the expression of the MTHFR 1298 polymorphism, the the
      risk factors of cervical cancer were analyzed. RESULTS: (1) The level of the
      folic acid in the cancer group was (13.29 +/- 8.47) nmol/L, lower than that of
      the control group [(16.75 +/- 7.92) nmol/L] (P = 0.001). The ratio of the
      positive result of the human papillomavirus (HPV) in the cancer group was 73.6%,
      higher than that of the control group (25.7%) (chi2 = 75.178, P = 0.001). What's
      more, the ratio of the first parturition age below 25 years old in the cancer
      group was 68.22%, also higher than the ratio of the control group (54.2%) (chi2 =
      6.556, P = 0.001). (2) The difference of the distribution of MTHFR 1298
      polymorphism between the two groups was significant (chi2 = 12.466, P = 0.002),
      contrast with the women whom had the MTHFR 1298AA, the women whom carried the
      MTHFR 1298AC had much more risk to get the cervical cancer (OR = 1.831, 95% CI:
      1.309-2.562), so did the women whom carried the MTHFR 1298CC (OR = 5.804, 95% CI:
      2.187-15.405). (3) After combining the two gene types which were the MTHFR 1298AA
      and the MTHFR 1298AC into one group, the difference of the distribution of the
      MTHFR 1298 polymorphism between the cancer group and the control group was also
      significant (chi2 = 4.527, P = 0.033), OR = 4.650 (95% CI: 1.129-19.150).
      CONCLUSION: The occurrence of the cervical cancer may associate with the low
      level of the folic acid and the first parturition age below 25 years old.
      Meanwhile, the MTHFR 1298 polymorphism may be an important factor to the
      occurrence of cervical cancer, the MTHFR 1298AC or MTHFR 1298CC may increase the
      risk to get the cervical cancer, especially the MTHFR 1298CC genotype.

PMID- 24749353
TI  - [Parental smoking and adolescent smoking: the intergenerational transmission of
      heath-risk behaviors].
AB  - OBJECTIVE: To determine the impact of parental smoking on adolescent smoking.
      METHODS: Data were retrieved from the China Health and Nutrition Surveys. Both
      Logistic regression and Tobit regression analyses were performed to estimate the
      intergenerational effects. RESULTS: The prevalence of adolescent smoking was
      2.35%. The Logistic regression results showed that parental smoking was a risk
      factor for adolescent smoking. Estimations from Tobit regression showed that
      father smoking was also correlated with the numbers of cigarettes adolescent
      smoked. CONCLUSION: An intergenerational effect was observed between parental
      smoking and adolescent smoking. In order to reduce adolescent smoking, parental
      smoking control should be targeted.

PMID- 24749354
TI  - [A multi-center, randomized, double-blind, positive controlled clinical trial of
      salbutamol sulfate MDI without CFC in the treatment of asthma].
AB  - OBJECTIVE: To evaluate the efficacy and safety of domestically produced
      Salbutamol Sulfate metered dose inhaler (MDI) without chloro-fluro-carbon (CFC)
      in the treatment of asthmatic patients. METHODS: A muticenter, randomized, double
      blind, positive controlled clinical trial was conducted in asthmatic patients.
      The participants were randomized divided into trial group treated with
      domestically produced Salbutamol Sulfate Aerosol MDI (200 microg single-dose) and
      control group treated with imported Salbutamol Sulfate Aerosol MDI (200 microg
      single-dose). The lung function was measured by spirometry and a scoring
      questionaire before medications and 15, 30, 120 and 240 min post medications.
      RESULTS: A total of 238 patients were enrolled in the trial. Compared with
      baselines, the forced expiratory volume in 1 s (FEV1) of the participants in both
      groups increased significantly 15, 30, 120 and 240 min after medications (P <
      0.05). There was no significant difference in the changes of FEV1 between the two
      groups (P > 0.05). Similarly, the forced vital capacity (FVC) and asthma
      symptomatic scores of the participants in both groups improved significantly
      after administration of medications (P < 0.05). There was no significant
      difference in the ratio of adverse reactions between the two groups (P > 0.05).
      In both groups, drugs were well tolerated. CONCLUSION: The domestically produced
      Salbutamol Sulfate Aerosol MDI without CFC is effective and safe for treating
      asthma.

PMID- 24749355
TI  - [The diagnostic value of serum beta-hydroxybutyrate in diabetic ketosis or
      diabetic ketoacidosis].
AB  - OBJECTIVE: To determine the diagnostic value of serum beta-hydroxybutyrate
      (betaOHB) in diabetic ketosis or diabetic ketoacidosis. METHODS: We conducted a
      retrospective review of clinical data, in West China Hospital from May 2011 to
      May 2013, of 1 209 patients with non-ketosis diabetics (DM group), 262 patients
      with diabetic ketosis or diabetic ketoacidosis (DK/DKA group), and 480 healthy
      people undergoing routine medical examinations (normal control group). Logistic
      regression analyses and ROC curves were performed in determining the diagnostic
      value of betaOHB for DK/DKA. RESULTS: The level of serum betaOHB was much higher
      in the DK/DKA patients than that of the participants in the DM group and normal
      control group (P < 0.01). The serum betaOHB turned negative earlier than urine
      ketone (P < 0.01) in the DK/DKA patients. The logistic regression analysis
      indicated that betaOHB was one of the independent risk factors for DK/DKA. The
      betaOHB had an area under of 0.975 in ROC curve, with 1 mmol/L [sensitivity
      (Sen.) 85.1%, specificity (Spe.) 95. 3%, positive predictive value (PV+) 80.36%,
      negative predictive value (PV-) 96.89%] as a diagnostic point for DK/DKA and 0.66
      mmol/L (Sen. 95%, Spe. 89.2%, PV+ 66.41%, PV- 99.9%) as a screening point.
      CONCLUSION: Diabetic patients with a level or higher than 1 mmol/L serum betaOHB
      can accurately predict DK/DKA. Patients with a level or lower than 0.66 mmol/L
      serum betaOHB are unlikely to have DK/DKA.

PMID- 24749356
TI  - [Study of glycated albumin cut-off point in diabetes mellitus and impaired
      glucose regulation].
AB  - OBJECTIVE: To investigate the cut-off point of glycated albumin (GA) in the
      detection of diabetes mellitus (DM) and impaired glucose regulation (IGR).
      METHODS: This study was conducted in 20-84 years-old adults who had risk factors
      of diabetes but no previously diagnosed diabetes. There were finally 392
      individuals included and received the measurement of GA and HbA1c. Receiver
      operating characteristic curve (ROC) was plotted to determine the performance of
      GA. RESULTS: (1) Based on the diabetes diagnosis criteria of WHO (1999), the
      subjects were divided into DM group (n = 131), IGR group (n = 126), and normal
      glucose tolerance (NGT) group (n = 135). The GA level in the three groups tended
      to increase (P < 0.05). (2) Spearman correlation analysis demonstrated that GA
      was positively correlated with glycated haemoglobin A1c (HbA1c) (r = 0.942 1, P <
      0.05), fasting plasma glucose (FPG) (r = 0.856 6, P < 0.05) and 2 h post-load
      plasma glucose (2-hPG) (r = 0.813 7, P < 0.05). (3) The mean levels of serum
      GA/HbA1c were 2.58 +/- 0.37, 2.44 +/- 0.37 and 2.17 +/- 0.25 for DM, IGR and NGT
      respectively. (4) The optimal cut-off points for detecting diabetes were 16.6% in
      GA [area under the carve (AUC) = 0.888], producing the sensitivity of 71.8% and
      the specificity of 87.4%. CONCLUSION: GA as a single screening test shows
      adequate to detect newly diagnosed DM, and the optimal GA cut-off point was 16.6%
      in this study.

PMID- 24749357
TI  - [Establishment of composite reference intervals for thyroid-stimulating hormone
      and free thyroxine in determination of subclinical hypothyroidism].
AB  - OBJECTIVE: To detect changes of thyroid stimulating hormone (TSH) with gender,
      age and levels of thyroid peroxidase antibodies (TPO-Ab) in patients with
      subclinical hypothyroidism, and to establish composite reference intervals for
      TSH and free thyroxine (FT4) in determination of subclinical hypothyroidism.
      METHODS: From Oct. 2011 to July 2012, 7 964 healthy people (males: 4 789,
      females: 3 175) undergoing medical examinations were recruited. Their serum
      levels of TSH and FT4 were determined. Of those participants, 794 were also
      tested for TPO-Ab. The serum TSH and FT4 data were transformed into normal
      distributions, with outliers being eliminated and a correction for skewness (0.
      909 and 0. 384, respectively) and kurtosis (2.605 and 1.947, respectively). The
      composite reference intervals were established according to the Mahalonobis
      distance formula. RESULTS: Serum TSH increased with age and TPO-Ab. Using the
      conventional reference standards, 358 participants were identified with
      subclinical hypothyroidism, which included 230 at 41-70 years of age and 43
      showing TPO-Ab positive. In contrast, using composite reference intervals, 301
      participants were identified with subclinical hypothyroidism, which included 142
      at 41-70 years of age and 25 showing TPO-Ab. CONCLUSION: The conventional cutoff
      values for FT4 and TSH separately lead to overestimation of the prevalence of
      subclinical thyroid disease.

PMID- 24749358
TI  - [Characteristics of mediastinal lymph nodes enlargement determined by contrast
      enhanced multi-detector CT in patients with sarcoidosis].
AB  - OBJECTIVE: To determine the enhancement patterns and anatomic distribution of
      enlarged mediastinal lymph nodes using contrast-enhanced multi-detector CT (MDCT)
      in patients with sarcoidosis. METHODS: We reviewed the contrast-enhanced MDCT
      features of 39 patients with pathologically or clinically diagnosed sarcoidosis,
      including the size, morphology, attenuation, enhancement patterns, and anatomic
      distribution of the enlarged mediastinal lymph nodes. RESULTS: Of the 39
      patients, 85% showed homogenous enhancement and 15% showed homogenous mixed with
      peripheral enhancement. The enlarged lymph nodes were predominantly distributed
      in the regions of 10R (95%), 10L (90%), 2R (69%), 7 (69%), and 5 (58%).
      CONCLUSION: Contrast-enhanced MDCT can detect the enhancement patterns and
      predominant anatomic distribution of enlarged mediastinal lymph nodes, which is
      of great value for the diagnosis of sarcoidosis.

PMID- 24749359
TI  - [Negative symptoms predict the improvement of social functioning of patients with
      schizophrenia].
AB  - OBJECTIVE: To identify predictive factors associated with the improvement of
      social functioning of schizophrenia patients in a community. METHODS: 101
      schizophrenia patients undergoing community rehabilitation were assessed with the
      Positive and Negative Syndrome Scale (PANSS), Personal and Social Performance
      Scale (PSP), Self-Esteem Scale (SES), Family Function Questionnaire (APGAR), and
      the World Health Organization Disability Assessment Scale II (WHODAS-II) twice 6
      months apart. Pearson correlation and hierarchical multiple linear regression
      analyses were performed to identify the influencing and predictive factors
      associated with the improvement of social functioning. RESULTS: The increase of
      PSP score was correlated with age (r = 0.220), reduced PANSS negative score (r =
      0.468), reduced PANSS general score (r = 0.392), reduced PANSS total score (r =
      0.472), and reduced WHODAS-II Score (r = 0.247). The predictive factors of the
      change of PSP score followed the following order: change of PANSS negative score
      [the change of coefficient of determination (deltaR2 ) = 0.197], age of onset
      (deltaR2 = 0.048), change of WHODAS-II score and psychiatric rehabilitation
      (deltaR2 = 0.031). CONCLUSION: Improvement of negative symptoms predicts the
      short-term improvement of social functioning of schizophrenia patients.

PMID- 24749360
TI  - [Advances and improvements in the diagnoses and treatments of lung cancer].
AB  - Lung cancer is the leading cause of cancer-related death worldwide. The topics of
      this issue include the changes of lung cancer epidemiology and its histological
      characteristics, the value of low dose CT in early detection of lung cancer and
      the image characteristics of solitary pulmonary nodule in early diagnosis of lung
      cancer, the advances in the therapeutic strategies for lung cancer with brain
      metastases and pulmonary sarcomatoid carcinoma, and new potential targets of
      molecular targeted therapy in lung cancer. In order to more effectively improve
      the survival and prognosis of the patients with lung cancer, it is necessary to
      strengthen basic research on the molecular pathogenesis of lung cancer, and to
      translate the advances in basic research into the efforts of exploring the
      specific and sensitive diagnosis tools for lung cancer, and so increasing the
      accuracy of early screening and diagnosis, as well as classifying the lung cancer
      by molecular pathology to achieve individualized therapy.

PMID- 24749361
TI  - [Construction of sh-rpS6 lentivirus vectors and its effect on proliferation in
      lung adenocarcinoma A549 cell lines].
AB  - OBJECTIVE: To construct the sh-rpS6 lentivirus vector targeting ribosomal protein
      S6 (rpS6) and explore its effect on proliferation in lung adenocarcinoma A549
      cell lines. METHODS: Sequences targeting the rpS6 gene were selected. The double
      strand shRNA oligo was ligated to pGCsil-GFP lentivirus vector and transformed
      into E. coli. The resulting recombinant vector was verified by sequencing. After
      transfection and lentivirus packing, the viral particles were collected and
      infected A549 cells. After selection of GFP positive cells by FACS, mRNA and
      protein expression levels of rpS6 were determined by real time PCR and Western
      blot. In the following experiment, the proliferation changes of A549 cell lines
      after the interference by sh-rpS6 was investigated by using CCK-8 kit. RESULTS:
      The sequencing result confirmed that pGCsil-sh-rpS6-GFP vector was successfully
      developed. Stably transfected A549 cell lines by sh-rpS6 were selected through
      FACS, with a selection ratio of 86.80%. The silencing effects of sh-rpS6 were
      determined by real time PCR and Western blot, suggesting that mRNA and protein
      expression of rpS6 in the targeted cells reduced by (79.72 +/- 6.83) % and (83.77
      +/- 12.13) %, significantly lower than those of control groups. In vitro showed
      the cell proliferation with sh-rpS6 was significantly slower than that of
      controls (P < 0.05). CONCLUSION: The constructed sh-rpS6 lentivirus vector could
      inhibit the expression of rpS6 in A549 cell lines effectively and significantly
      slow the cell proliferation in vitro.

PMID- 24749362
TI  - [Construction and expression of recombinant lentiviral vectors of AKT2,PDK1 and
      BAD].
AB  - OBJECTIVE: To construct human protein kinase B (ATK2), phosphoinositide-dependent
      kinase 1 (PDK1) and bcl-2-associated death protein (BAD) lentiviral expression
      vector, and to determine their expressions in 293T cells. METHODS: Total RNA was
      extracted from lung cancer tissues. The full-length coding regions of human ATK2,
      BAD and PDK1 cDNA were amplified via RT-PCR using specific primers, subcloned
      into PGEM-Teasy and then sequenced for confirmation. The full-length coding
      sequence was cut out with a specific restriction enzyme digest and subclone into
      pCDF1-MCS2-EF1-copGFP. The plasmids were transfected into 293T cells using the
      calcium phosphate method. The over expression of AKT2, BAD and PDK1 were detected
      by Western blot. RESULTS: AKT2, PDK1 and BAD were subcloned into pCDF1-MCS2-EF1
      copGFP, with an efficiency of transfection of 100%, 95%, and 90% respectively.
      The virus titers were 6.7 x 10(6) PFU/mL in the supernatant. After infection, the
      proteins of AKT2, PDK1 and BAD were detected by Western blot. CONCLUSION: The
      lentivial vector pCDF1-MCS2-EF1-copGFP containing AKT2, BAD and PDK1 were
      successfully constructed and expressed in 293T cells.

PMID- 24749363
TI  - [REGgamma promotes malignant behaviors of lung cancer cells].
AB  - OBJECTIVE: To determine the expression of proteasome aotivator gamma (REGgamma)
      in human lung cancer tissues and cell lines and its association with malignant
      biological behaviors. METHODS: Immunohistochemistry (IHC) was used to detect the
      expression of REGgamma in lung cancer and normal lung tissues. The expressions of
      REGgamma in lung cancer cells and normal epithelial cells were determined by
      Western blot. The H1975 lung cancer stable cell lines with different levels of
      REGgamma expression were constructed and their proliferations were evaluated by
      MTT assay. PI staining was used to assess the influence of REGgamma on cell
      growth cycle. The effect of REGgamma on the migration of lung cancer cells were
      observed with the cell scratch experiment. RESULTS: Lung cancer tissues had
      significantly higher levels of REGgamma expression than normal tissues.
      Similarly, lung cancer cell lines showed higher levels of REGgamma expression
      than the normal epithelial cell line. The overexpression of REGgamma enhanced
      cancer cell proliferations (P < 0.05), promoted more cells into the S+G2/M phase
      (P < 0.05) and promoted the migration of cancer cells (P < 0.05). All of these
      effects were reversed after suppression of REGgamma. CONCLUSION: REGgamma
      facilitates malignant biological behaviors of lung cancers.

PMID- 24749364
TI  - [Clinical epidemiology and histological characteristics of patients with lung
      cancer in West China Hospital of Sichuan University].
AB  - OBJECTIVE: To identify changes in patterns of primary bronchogenic carcinoma.
      METHODS: We reviewed clinical data of patients with primary bronchogenic
      carcinoma, who were identified as permanent residents of Sichuan province and
      were treated in West China Hospital of Sichuan University in 2000 and 2010. The
      distributions of gender, age, urban/rural residency, smoking history,
      occupational exposure and histological types of tumor were compared between the
      2000 group and 2010 group. RESULTS: A total of 2 167 patients (616 in 2000 and
      1551 in 2010) met the inclusion criteria. Compared with the 2000 group, the 2010
      group had a lower proportion of male patients (male/female sex ratio dropped from
      2.78:1 to 2.13:1, P = 0.013), more patients from medium and small sized cities
      (patients from large city decreased from 42.1% to 32.0%, P < 0.001, and patients
      from medium and small sized cities decreased from 39.9% to 31.7%, P < 0.001),
      more patients from rural areas (patients from townships increased from 5.5% to
      8.1%, P = 0.041, and patients from villages increased from 12.5% to 28.2%, P <
      0.001). No significant difference in age was found in the two cohorts of
      patients. The proportion of squamous cell carcinoma dropped from 44.8% in 2000 to
      28.7% in 2010 (P < 0.001). The proportion of adenocarcinoma increased from 43.0%
      in 2000 to 53. 1% in 2010 (P < 0.001). The proportion of small cell lung cancer
      increased from 3.7% in 2000 to 11.9% in 2010 (P < 0.001). The proportion of
      squamous cell carcinoma in male patients was higher than that of female patients
      (60.7% vs. 36.6% in 2000; 75.8% vs. 42.9% in 2010). The proportion of
      adenocarcinoma was higher in female patients than that of male patients (60.7%
      vs. 36.6% in 2000; 75.8% vs. 42.9% in 2010). The proportion of squamous cell
      carcinoma was higher in elderly patients (> or = 60) than that of young patients
      (< 45) (50.5% vs. 33.8% in 2000; 30.2% vs. 15.6% in 2010). The proportion of
      adenocarcinoma in young patients was higher than of elderly patients (54.9% vs.
      36.9% in 2000; 57.1% vs. 51.8% in 2010). Squamous cell carcinoma was predominate
      in smoking patients (55.6% in 2000; 40.9% in 2010). Adenocarcinoma was
      predominate in no-smoking patients (58.4% in 2010; 75.7% in 2010) and the
      patients exposed to risk occupations (46.2% in 2000; 60.2% in 2010). CONCLUSION:
      Over the past decade, the percentages of female patients, adenocarcinoma and
      small cell lung cancer increased significantly in the patients with lung cancer.
      Male gender, old age (> or = 60) and smoking are risk factors of squamous cell
      carcinoma. Female gender, young age (< 45) and occupational exposure are risk
      factors of adenocarcinoma.

PMID- 24749365
TI  - [Value of fGGO in diagnosing stage I lung cancers].
AB  - OBJECTIVE: To determine the value of focal area of ground-glass opacity (fGGO)
      for early detection and diagnosis of lung cancers. METHODS: We reviewed clinical
      data of all patients whose chest CT images showed isolated lesions < or = 5 cm in
      diameter in the Department of Chest Surgery at West China Hospital, Sichuan
      University between 2007 and 2010. According to the volume of solid components,
      the lesions were classified as pure ground-glass opacity (pGGO), mixed ground
      glass opacity (mGGO) or solid lesions. The malignant ratio and stage of lesions
      were calculated based on the postoperative pathological tests. The
      characteristics of CT signs were compared between the benign and malignant
      lesions. RESULTS: Of the 202 cases, 63 (included 15 pGGO and 48 mGGO) had fGGO
      with a malignant ratio of 71.4% (45/63). The percentage of malignant tumors in
      the mGGO, pGGO and solid lesions was 75.0%, 60.0% and 48.2% respectively. Stage I
      lung cancers had an occurrence of spiculation, lobulation and vascular
      convergence in fGGO of over 70%, higher than that of the benign tumors (P <
      0.05). CONCLUSION: fGGO is an important indicator of lung cancer. mGGO is highly
      likely to be malignant, particularly when one or more signs of spiculation,
      lobulation and vascular convergence appear.

PMID- 24749366
TI  - [Outcomes of treatment of 32 cases of advanced or relapsed post-surgery pulmonary
      sarcomatoid carcinoma].
AB  - OBJECTIVE: To determine the efficacy of the third generation chemotherapy agents
      on relapsed post-surgery and advanced pulmonary sarcomatoid carcinoma (PSC).
      METHODS: We reviewed the medical records of 32 PSC patients. Their treatment
      modalities and survival rate, as well as risk factors associated with the
      survival rate including gender, age, location and size of tumor, relapse, initial
      diagnosis of stage, pathologic subtypes and smoking history were analysed.
      RESULTS: All of the 32 PSC patients received chemotherapy with gemcitabine
      combined with cisplatin (GP) or paclitaxel combined with cisplatin (TP). They had
      a median of 14 months overall survive (OS) and 5 months progress-free survive
      (PFS). The remission rate was 21.9%. An initial stage IV diagnosis and a larger
      than 6 cm tumor in diameter were independent factors associated with poor
      prognosis. CONCLUSION: The efficacy of TP and GP chemotherapy on patients with
      relapsed post-surgery and advanced PSC is comparable with that reported by other
      researchers. An initial stage IV diagnosis and a larger than 6 cm tumor in
      diameter are predictors of poor prognosis.

PMID- 24749367
TI  - [Determination of organochlorine pesticides in water using solidification of
      floating organic drop liquid phase microextraction by gas chromatography].
AB  - OBJECTIVE: To develop a new method for simultaneous determination of eight
      organochlorine pesticides (OCPs) in water samples using solidification floating
      organic drop liquid-phase microextraction (SFO-LPME) combined with gas
      chromatography-electronic capture detector (GC-ECD). METHODS: The experimental
      conditions of SFO-LPME were determined with n-Hexadecane as extractant, water
      samples adjusted to pH 6.0, inonic strength increased by adding 15.0 g/100 mL
      NaCI. The OCPs were extracted at 55 degrees C for 10 mm and determined with GC
      ECD. RESULTS: A good linearity (correlation coefficients > or = 0.996) was
      obtained for eight target compounds from 5 ng/I. to 100 ng/L. The method
      detection limits ranged from 0.24 ng/L to 0.78 ng/L. Satisfactory results were
      achieved with samples of river water, piped water and farmland water, with an
      average recovery of 76.0%-106.0% and RSD of 3.24%-11.60%. CONCLUSION: The
      proposed method is rapid, simple and sensitive. It is suitable for hatch analyses
      of eight organic chlorine pesticides in water samples.

PMID- 24749368
TI  - [Clinical value of dual-source CT angiography in the diagnosis of postoperative
      aortic intramural hematoma in patients with endovascular stent-graft exclusion
      surgery].
AB  - OBJECTIVE: To determine the clinical value of dual-source CT angiography (DSCTA)
      in the diagnosis of postoperative aortic intramural hematoma (AIMH) in patients
      with endovascular stent-graft exclusion (EVE) surgery. METHODS: Between Oct 2008
      and May 2013, thirty-six patients were diagnosed with AIMH by DSCTA, and 12 of
      these patients with type B underwent EVE. The 12 patients were followed up with
      DSCTA, which included imaging reconstruction (multi-plane reconstruction, MPR),
      maximum intensity projection (MIP) and volume rendering technique (VRT). The
      extent and type of AIMH, aortic ulcers and the outcomes and complications of AIMH
      were observed. RESULTS: The 36 cases of AIMH included 11 Stanford type A and 25
      type B. No tearing intimal flap or contrast materials within the hematoma were
      observed. The maximum aortic diameter of the hematoma areas varied from 3.8 to
      5.4 cm (average 4.3 cm) and the maximum thickness of the hematoma ranged from 0.5
      cm to 1.3 cm (average 0.9 cm). The ratio between the minimum and the maximum
      diameter of the aortic lumen in the hematoma areas ranged from 0. 74 to 0. 98
      (average 0.85). Aortic ulcers were revealed in 3 patients with type A AIMH and 8
      patients with type B AIMH. Intimal tearing of distal abdominal aorta was found in
      3 patients with type B AIMH. In the 12 patients underwent EVE surgery, hematoma
      shrank in all cases with 4 cases almost resolving and aortic ulcers in the area
      of stent-graft exclusion disappeared in 3 cases. The form of stent-graft appeared
      normal in 9 cases and slightly abnormal in 3 cases. Fluent main branches of
      aortic arch and none existence of stent endoleaking were observed. CONCLUSION:
      DSCTA with handy, effective and non-invasive advantages is one of the important
      imaging methods in the diagnosis of AIMH in patients with EVE surgery.

PMID- 24749369
TI  - [Therapeutic effects of umbilical cord mesenchymal stem cells transplantation on
      systemic lupus erythematosus].
AB  - OBJECTIVE: To observe the efficacy of umbilical cord mesenchymal stem cells (UC
      MSCs) transplantation for the patients with refractory systemic lupus
      erythematosus (SLE). METHODS: Thirty seven patients with SLE were enrolled in
      this study, and divided into conventional treatment group (control group, n = 20)
      and UC-MSCS adjuvant treatment group (treatment group, n= 17). All the patients
      in both two groups were treated with glucocorticoids and cyclophosphamide (CTX).
      In the UC-MSCs group, each patient additionally received the transplantation of 3
      x 10(7) UC-MSCs infusion intravenously. The clinical manifestations and
      laboratory parameters of each patient were observed before the treatments and 2
      weeks, 1 month, 2 months, 3 months, months,9 months and 12 months after the
      treatments. RESULTS: All the 37 patients were observed for 12 months. 24 h
      urinary protein excretion (U-Pro), anti nuclear antibody (ANA), erythrocyte
      sedimentation rate (ESR), high-sensitivity C-reactive protein (hs-CRP), systemic
      lupus erythematosus disease activity index (SLEDAI) of these two groups decreased
      significantly (P < 0.05). serum albumin (ALB), C3, and C4 of two groups were
      higher after the treatments (P < 0.05). ALB and C3 in treatment group exceeded
      the control group (P < 0.05). The positive rates of Anti-dsDNA in control and
      treatment group were 40% and 10% respectively, while the recurrence rates were
      50% and 20% respectively, these difference between the two groups were
      statistically significant (P < 0.05). There were no transplantation related
      complications observed. CONCLUSION: UC-MSCs transplantation could be effective
      and safe for refractory SLE on basis of glucocorticoid and cyclophosphamide
      therapy.

PMID- 24749370
TI  - Soil microbes and soil respiration of Mongolian Steppe soils under grazing
      stress.
AB  - Soils of Northern China were analysed for their microbiological and soil physical
      properties with respect to different grazing stress. An important factor for this
      is soil compaction and related aeration due to pore size shifts. Bulk density
      increases significantly with increasing grazing intensity and soil carbon
      contents show decreasing values from top to depth. Organic carbon (LOI)
      concentrations decrease significantly with increasing grazing intensity. The data
      on LOI (2-5.8%) approximate 10-30 mg C, our data on glucose show values between
      0.4-1.2 mg, i.e. approx. 4% of total carbon. Numbers and biomass of bacteria show
      generally a decreasing trend of those data at grazed and ungrazed sites, numbers
      range between 0.4 and 8.7 x10(8) g(-1) d.wt., bacterial biomass between 0.4 and
      3.8 microg Cg(-1). This need to be recorded in relation to soil compaction and
      herewith-hampered aeration and nutrient flow. The temperature-respiration data
      also allow getting an idea of the Q10-values for soil respiration. The data are
      between 2.24 (5-15 degrees C) and 1.2 (25-35 degrees C). Our data are presented
      with a general review of biological properties of Mongolian Steppe soils.

PMID- 24749371
TI  - Study of ranking of bio-indices using benthic macroinvertebrates for Lower
      Dongnai River System, Vietnam.
AB  - It has been demonstrated by research that the most successful assessment methods
      have been based on the benthic macroinvertebrate communities. A lot of bio
      indices have been applied to evaluate the water quality widely. However, most of
      them have got the rankings for the water quality assessment. In this study, based
      on the monitoring results of the benthic macroinvertebrate and the environmental
      parameters in the Lower Dongnai River System during three-year periods (2007 -
      2009), the linear correlations among the most popular bio-indices and each
      environmental parameter were considered. These environmental variables having the
      most closed correlation with the biological indices were DO (dissolved oxygen),
      WQI (water quality index) and total nitrogen. From the analysis, the ranking of
      bio-indices using benthic macroinvertebrate for the Lower Dongnai River System
      were established. The findings proved that the ranking of bio-indices for water
      quality assessment can be used to evaluate the water quality for the Lower
      Dongnai River System.

PMID- 24749372
TI  - Assessment of pollutants and gaseous emissions in sewer network in NCT of Delhi.
AB  - The NCT of Delhi in India handles domestic sewage through a long sewerage
      networks. The network is into eight divisions. The aim of the present study is to
      arrive at a correlation between sewage quality and gas emissions in the sewer
      network of various divisions. This will aid in forewarning the sewer workers
      about the safety precautions. The health effects due to toxic sewer gases
      exposure and assessment of hazardous conditions and hazard potential are
      discussed. The study areas were broadly classified as residential, commercial,
      industrial and mix (combination of residential & commercial) for comparison.
      Sewage samples were collected from 1020 sites and analyzed for 10 different
      physicochemical parameters. The analytical data revealed wide variation in the
      chemical composition of sewage flowing at various sewerage network sites. Based
      on comparison with the regulatory standard for discharge in sewers, 89 sites with
      higher values of BOD and sulphate were marked as critical sites. Subsequently,
      the concentrations of CH4 and H2S in sewer emissions were determined for the 89
      critical sites through onsite monitoring. Samples from 22 sites had significantly
      higher concentration of CH4 than the LEL and those from 40 sites showed
      concentrations higher than the LFL. On the other hand, samples from 38 locations
      showed significantly high H2S concentration, more than permissible limit of 10
      ppm. The sewer workers in North East, North West and West region of the
      metropolis were exposed to hazards from excessive CH4 and H2S emissions, whereas
      those under South and South West regions were more vulnerable to H2S related
      risks. The sewer network under North, Central and South poses relatively less
      hazard with regard to gaseous emissions.

PMID- 24749373
TI  - Assessment of coastal water quality at Bakkhali, West Bengal (India).
AB  - Spatial variations of some physico-chemical water quality of the coastal water of
      a segment of Bakkhali (Bay of Bengal) were studied between the months of November
      2009 and February 2010 before 12:00 a.m. The studies were carried out at three
      coastal sites of Bakkhali Beach (south extreme point, middle point and far north
      point, about 1.2 km along the shore) which is influenced by anthropogenic input
      from land-based sources. The site receives domestic, agricultural and industrial
      wastes. The water is being used for fishing, transportation of goods and by
      people for several purposes. The banks of the estuarine channels have
      traditionally been preferred locations for human settlement. Considering the
      various uses of this coastal segment, between Bakkhali to Haldia, the studies
      related to water quality monitoring were carried out. The pH, temperature,
      turbidity, salinity, TDS and conductivity vary in range of 8.24 - 8.65, 27.5
      degrees C-31.5 degrees C, 480 NTU - 808 NTU, 21.6 PSU-30.0 PSU, 676 mg/L -934
      mg/L and 1.72 mS/cm -1.97 mS/ cm respectively. Dissolved oxygen, biochemical
      oxygen demand (BOD) concentrations at different sites vary within a narrow range
      6.05 mg/L - 8.1 mg/L and 1.05 mg/L - 3.0 mg/L respectively. Chemical oxygen
      demand concentrations vary in a wide range of 170 mg/L - 812 mg/L. The bacterial
      count at the sampling site varied from 76-150 CFU.

PMID- 24749374
TI  - Geostatistical assessment of nitrate in groundwater of Puri City, India.
AB  - Groundwater quality is a major concern for assuring safe public health in terms
      of nitrate concentration. The objective of study was precise modeling of spatial
      variation of nitrate in groundwater using geostatistical analysis. To account for
      the uncertainty of the prediction, Kriging interpolation method was applied. The
      best Kriging method and semivariogram model were identified with optimum values
      of parameters to model the nitrate variation in groundwater. Accuracy of model
      was checked by error gauges and consistency of ground truth values with predicted
      values. Finally prediction and error maps of nitrate in groundwater were
      generated using Ordinary Kriging. The study reflects the importance of quality
      data and significance of geostatistical analysis for groundwater planning and
      management.

PMID- 24749375
TI  - Limnological study with reference to fish culture of Bothali (Mendha) reservoir,
      district - Gadchiroli (India).
AB  - Limnological study with reference to fish culture was carried out at Bothali
      (Mendha) reservoir, district Gadchiroli, India. Water samples from different
      sampling locations were collected and processed for physico-chemical analysis.
      The physico-chemical analysis revealed that the reservoir is favourable for fish
      culture as the phosphate content in water is moderate in amount. This reservoir
      can produce a good yield of fishes. Though the reservoir is presently exploited
      and is under pisciculture, a better treatment of the reservoir such as prevention
      of entry of organic matter, reduction of phosphate ion concentration to certain
      extent is necessary to obtain a maximum fish yield.

PMID- 24749376
TI  - Changes in oxygen consumption rates of snail Indoplanorbis exustus (DESHAYAS)
      exposed to sublethal concentrations of fungicide Contaf Plus.
AB  - Snails Indoplanorbis exustus, were exposed to 4.8 mg/L (1/10th of 96 hL50) and
      9.6 mg/L (1/5th of 96 hLC50) of Contaf Plus. Initially at 24 hours, at both the
      concentrations, increase in oxygen consumption rate is noted. At 48 hours stage,
      an increase in oxygen consumption rate is noticed at lower concentration, while
      at higher concentration the oxygen consumption was found to be reduced. At 72
      hours stage, in both the sublethal concentrations reduction in oxygen consumption
      is noted. At the end of 96 hours, again in both the concentration an increase in
      oxygen consumption prevailed. These experimental snails., upon transfer to fresh
      water for 24 hours., showed decreased oxygen consumption rate. Oxygen consumption
      rates are discussed in this paper with respect to sublethal concentration and
      time of exposure to toxicant.

PMID- 24749377
TI  - Mercury content in low cost skin lightening cream products.
AB  - Skin lightening creams were randomly collected from local markets in Sultanate of
      Oman for analysis of mercury (II) content. All the products collected were of low
      cost imported materials from different countries. Cream samples were digested in
      nitric acid and hydrogen peroxide at elevated temperature using a microwave
      digester. The mercury content was measured using Flow Injection Atomic
      Spectroscopy (FIAS)-Mercury Hydride System. Out of forty cream samples analyzed,
      about one fourth of the samples contained higher levels of mercury which is more
      than the maximum mercury content of 1 microg/g permitted by the Food and Drug
      Administration regulation. The mercury level in the analyzed samples is found to
      be in the range from 0.02 to 25.7 microg/g. Among the analyzed skin lightening
      cream samples half of the materials did not have any detectable mercury content.

PMID- 24749378
TI  - Physiological and biochemical adverse effects of heavy metals on Brassica
      oleracea grown in Sanganer area, India.
AB  - The paper reveals results of a study carried out in agricultural fields of
      Sanganer town in India. This town is situated 20 km away from the heart of Jaipur
      city. In the study area (Amanishah Nalla Sanganer, Jaipur) vegetables are grown
      in the fields receiving sewerage and textile wastewater. Water, soil and crop
      (plant samples) were collected from the agricultural fields of Sanganer for
      analysis. Wastewater (from Amanishsh Nalla) used as irrigation water in
      agricultural fields of Sanganer town was found to contain 6.127 mg/ L of zinc,
      7.116 mg/L of Copper, 5.114 mg/L of Chromium and 4.774 mg/L of lead as the
      highest amount of respective heavy metals. Soil from agricultural fields was
      found to contain 11.247 mg/g of zinc, 6.410 mg/g of Copper, 3.514 mg/g of
      Chromium and 2.619 mg/g of lead. Brassica oleracea (plant material) grown in the
      Sanganer area was analysed for heavy metal contents. Plant fruit contained 5.730
      mg/g of zinc, 7.380 mg/g of Copper, 5.940 mg/g of Chromium and 2.170 mg/g of lead
      as the highest amount of heavy metals. Use of wasterwater alters the nutritional
      value of the vegetables grown here and in long run consumption of such vegetables
      may impose health hazards in human beings, which is a matter of concern.

PMID- 24749379
TI  - Optimisation of Lime-Soda process parameters for reduction of hardness in aqua
      hatchery practices using Taguchi methods.
AB  - This paper presents the optimisation of Lime-Soda process parameters for the
      reduction of hardness in aqua-hatchery practices in the context of M.
      rosenbergii. The fresh water in the development of fisheries needs to be of
      suitable quality. Lack of desirable quality in available fresh water is generally
      the confronting restraint. On the Indian subcontinent, groundwater is the only
      source of raw water, having varying degree of hardness and thus is unsuitable for
      the fresh water prawn hatchery practices (M. rosenbergii). In order to make use
      of hard water in the context of aqua-hatchery, Lime-Soda process has been
      recommended. The efficacy of the various process parameters like lime, soda ash
      and detention time, on the reduction of hardness needs to be examined. This paper
      proposes to determine the parameter settings for the CIFE well water, which is
      pretty hard by using Taguchi experimental design method. Orthogonal Arrays of
      Taguchi, Signal-to-Noise Ratio, the analysis of variance (ANOVA) have been
      applied to determine their dosage and analysed for their effect on hardness
      reduction. The tests carried out with optimal levels of Lime-Soda process
      parameters confirmed the efficacy of the Taguchi optimisation method. Emphasis
      has been placed on optimisation of chemical doses required to reduce the total
      hardness using Taguchi method and ANOVA, to suit the available raw water quality
      for aqua-hatchery practices, especially for fresh water prawn M. rosenbergii.

PMID- 24749380
TI  - Leaching behavior and effectiveness of curing days (7& 28) of
      solidified/stabilized fly ash based geopolymer (multi-metal bearing sludge):
      experimental and modeling study.
AB  - This paper presents the study of the immobilization of heavy metals like Pb, Fe,
      Mn, Cu and Zn by fly ash based geopolymers. The purpose of this study was to
      investigate the effectiveness of fly ash based geopolymeric
      solidification/stabilization technology. For S/S of waste, geopolymer as a
      binding agent was mixed with waste at different ratios. For initial waste
      characterization, contaminants concentration and some physical waste
      characterization such as dry density, bulk density, specific gravity, porosity,
      moisture holding capacity, and moisture content were determined. Waste and
      geopolymer mixture were cured for 7 and 28 days to study the effect of curing
      days on the solidified/ stabilized product. Diffusion leaching test was performed
      on the geopolymers containing industrial sludge to determine the leaching
      mechanism of binders to entrap the waste constituents within their matrix.
      Movement of the elements was identified with the help of leachability index. S/S
      through geopolymer was found to be effective in immobilizing toxic metals present
      in the sludge. Zn was 100% and other metals like Pb, Fe, Mn and Cu were in the
      range 80-99% immobilized. The order of fixation of metals was Zn >Cu > Fe > Mn >
      Pb.

PMID- 24749381
TI  - Removal of persistent organic pollutant hexachlorocyclohexane isomers by advanced
      oxidation process.
AB  - Organochlorine insecticide Lindane (gamma-Hexachlorocyclohexane) and its isomers
      (alpha, beta, delta-HCH) are recalcitrant and toxic compounds. They were
      progressively banished in most of the countries, because of their persistence and
      toxicity. Due to their nonselective production process and widespread use, they
      are still occurring in the environment. These insecticides and isomers were
      detected in all media like soil, ground water, sediments, vegetables and even in
      human tissues. In this study, UV, H2O2, UV+H2O2, Fenton's reagent, UV+Fenton's
      reagent, Advanced Oxidation Process (AOP) have been applied for degradation of
      HCH isomers (a, beta, gamma and delta-HCH). The results revealed that the UV+H2O2
      treatment was most effective, which could do 99% degradation of all isomers of
      HCH within 75 minutes. The results in detail are presented and discussed in this
      paper.

PMID- 24749382
TI  - A method to minimize the global warming and environmental pollution.
AB  - There has been continuous increase in the level of CO2 in atmosphere. Therefore,
      it is essential to develop an economical and convenient process to reduce the
      concentration of CO2 in the atmosphere. In this study, we have proposed an
      economical and efficient adsorption method to minimize the environmental CO2. A
      fluidized bed adsorption column was used, fabricated using cast iron sheet. The
      low prize pyrolyzed biochar prepared from farming biomass (crushed fine powder)
      was used as an adsorbent to adsorb CO2 from the mixture of air and CO2 (99.5% air
      and 0.5% CO2). The experimental observation was taken for the % removal of CO2
      from the mixture of air and CO2, development of adsorption isotherm and to study
      the effect of pressure and inlet gas flow rate on the amount of CO2 adsorbed per
      kg of biochar. The exhausted (CO2 adsorbed) biochar from the fluidized column was
      tested as a fertilizer for the wheat crop and it has given near about 10%
      increase in the height of wheat crop within the first 10 days after sowing the
      wheat seeds. On the basis of this experimentation, we have proposed a
      hypothetical method, using above mentioned fluidized bed column and biochar as
      adsorbent to reduce the CO2 concentration in the highly polluted regions.

PMID- 24749383
TI  - Isolation and characterization of Cr (VI) tolerant bacteria from tannery waste
      and its bioremediation potential.
AB  - The East Kolkata wetland, situated in West Bengal, India, is presently being
      exploited by housing many leather complexes surrounding the zone in and around.
      High amount of either untreated or partially treated liquid tannery wastes are
      discharged in the wetland. Treated effluent from some common effluent treatment
      plant (CETP) showed the presence of Cr (VI) exceeding the limiting concentration.
      Three different bacterial strains (L1, L2, and L3) were isolated from the treated
      effluent. Morphological and biochemical characterizations exhibited that they
      belong to Gram positive Bacillus group. All such strains proved to be chromate
      tolerant in the concentration ranging from 20 to 50 mg/L. Significant reduction
      in Cr (VI) was observed in all those strains, especially L3 [86.3% removal
      corresponding to 30 mg/L initial concentration]. Cytosolic fraction was involved
      in Cr reductase capacity. Molecular characterization by 16S rDNA genome
      sequencing of L3 [the most promising isolate, in terms of chromium (VI)
      tolerance] confirmed that the strain is Bacillus cereus GXBC-1.

PMID- 24749384
TI  - Review of various treatment methods for the abatement of phenolic compounds from
      wastewater.
AB  - Phenol and its derivatives are considered among the most hazardous organic
      pollutants from industrial wastewater and they are toxic even at low
      concentrations. Besides the existence of phenol in natural water source it can
      lead to the formation of other toxic substituted compounds. So this has led to
      growing concern on setting up of rigid limits on the acceptable level of phenol
      in the environment. The various methods for the treatment of phenol from
      wastewater streams are briefly reviewed. The various technologies like
      distillation, liquid-liquid extraction with different solvents, adsorption over
      activated carbons and polymeric and inorganic adsorbents, membrane pervaporation
      and membrane-solvent extraction, have been elucidated. The advantages and
      disadvantages of the various methods are illustrated and their performances are
      compared.

PMID- 24749385
TI  - Anaerobic sequencing batch reactors and its influencing factors: an overview.
AB  - Anaerobic sequencing batch reactors (ASBR) operate in four cyclic steps: feed,
      reaction, settling and discharge. ASBRs allow typical biological anaerobic
      metabolism from substrate consumption to methane and carbon dioxide production.
      Microorganisms in an ASBR are exposed to variable substrate concentrations over
      the duration of the cycle, resulting in high rates of substrate conversion and
      efficient biomass flocculation and settling. High substrate concentrations at the
      beginning of a cycle result in high metabolic activity and substrate removal. Low
      substrate concentrations towards the end of the cycle result in low biogas
      production and allow for good sludge settling. However, the cycles should be as
      frequent as possible while allowing for completion of each of the four stages.
      Operating by batches enables the solids residence time to be independent of the
      hydraulic retention time without recourse to a settling tank, since the reactor
      functions as a decanter whenever the stirring mechanism is turned off. This
      review presents an overview of the ASBR process and the various factors
      influencing its performance.

PMID- 24749386
TI  - Bacterial exopolysaccharide based magnetic nanoparticles: a versatile nanotool
      for cancer cell imaging, targeted drug delivery and synergistic effect of drug
      and hyperthermia mediated cancer therapy.
AB  - Microbial exopolysaccharides (EPSs) are highly heterogeneous polymers produced by
      fungi and bacteria that have garnered considerable attention and have remarkable
      potential in various fields, including biomedical research. The necessity of
      biocompatible materials to coat and stabilize nanoparticles is highly recommended
      for successful application of the same in biomedical regime. In our study we have
      coated magnetic nanoparticles (MNPs) with two bacterial EPS-mauran (MR) and
      gellan gum (GG). The biocompatibility of EPS coated MNPs was enhanced and we have
      made it multifunctional by attaching targeting moiety, folate and with
      encapsulation of a potent anticancerous drug, 5FU. We have conjugated an imaging
      moiety along with nanocomposite to study the effective uptake of nanoparticles.
      It was also observed that the dye labeled folate targeted nanoparticles could
      effectively enter into cancer cells and the fate of nanoparticles was tracked
      with Lysotracker. The biocompatibility of EPS coated MNPs and synergistic effect
      of magnetic hyperthermia and drug for enhanced antiproliferation of cancer cells
      was also evaluated. More than 80% of cancer cells was killed within a period of
      60 min when magnetic hyperthermia (MHT) was applied along with drug loaded EPS
      coated MNPs, thus signifying the combined effect of drug loaded MNPs and MHT. Our
      results suggests that MR and GG coated MNPs exhibited excellent biocompatibility
      with low cell cytotoxicity, high therapeutic potential, and superparamagnetic
      behavior that can be employed as prospective candidates for bacterial EPS based
      targeted drug delivery, cancer cell imaging and for MHT for killing cancer cells
      within short period of time.

PMID- 24749387
TI  - Improved biocompatibility of poly(lactic-co-glycolic acid) orv and poly-L-lactic
      acid blended with nanoparticulate amorphous calcium phosphate in vascular stent
      applications.
AB  - Biodegradable polymers used as vascular stent coatings and stent platforms
      encounter a major challenge: biocompatibility in vivo, which plays an important
      role in in-stent restenosis (ISR). Co-formulating amorphous calcium phosphate
      (ACP) into poly(lactic-co-glycolic acid) (PLGA) or poly-L-lactic acid (PLLA) was
      investigated to address the issue. For stent coating applications, metal stents
      were coated with polyethylene-co-vinyl acetate/poly-n-butyl methacrylate
      (PEVA/PBMA), PLGA or PLGA/ACP composites, and implanted into rat aortas for one
      and three months. Comparing with both PEVA/PBMA and PLGA groups after one month,
      the results showed that stents coated with PLGA/ACP had significantly reduced
      restenosis (PLGA/ACP vs. PEVA/PBMA vs. PLGA: 21.24 +/- 2.59% vs. 27.54 +/- 1.19%
      vs. 32.12 +/- 3.93%, P < 0.05), reduced inflammation (1.25 +/- 0.35 vs. 1.77 +/-
      0.38 vs. 2.30 +/- 0.21, P < 0.05) and increased speed of re-endothelialization
      (1.78 +/- 0.46 vs. 1.17 +/- 0.18 vs. 1.20 +/- 0.18, P < 0.05). After three
      months, the PLGA/ACP group still displayed lower inflammation score (1.33 +/-
      0.33 vs. 2.27 +/- 0.55, P < 0.05) and higher endothelial scores (2.33 +/- 0.33
      vs. 1.20 +/- 0.18, P < 0.05) as compared with the PEVA/PBMA group. Moreover, for
      stent platform applications, PLLA/ACP stent tube significantly reduced the
      inflammatory cells infiltration in the vessel walls of rabbit iliac arteries
      relative to their PLLA cohort (NF-kappaB-positive cells: 23.31 +/- 2.33/mm2 vs.
      9.34 +/- 1.35/mm2, P < 0.05). No systemic biochemical or pathological evidence of
      toxicity was found in either PLGA/ACP or PLLA/ACP. The co-formulation of ACP into
      PLGA and PLLA resulted in improved biocompatibility without systemic toxicity.

PMID- 24749388
TI  - Hybrid macroporous gelatin/bioactive-glass/nanosilver scaffolds with controlled
      degradation behavior and antimicrobial activity for bone tissue engineering.
AB  - A new composition of gelatin/bioactive-glass/silver nanoparticle was synthesized
      and employed to prepare antibacterial macroporous scaffolds with potential
      applications in bone tissue engineering. A set of macroporous nanocomposite
      scaffolds were developed from an aqueous solution of gelatin by freeze-drying and
      crosslinking using genipin at ambient temperature. Silver nanoparticles were
      successfully synthesized in situ in gelatin solution by heat treatment reduction
      as a simple and "green" method in which gelatin acted as a natural reducing and
      stabilizing agent. The effect of the incorporation of the bioactive-glass and the
      silver nanoparticle concentration on the physicochemical properties of the
      scaffolds, such as the gel fraction, porosity, in vitro enzyme degradation,
      morphology, and swelling behavior was studied. Furthermore, the in vitro
      viability of human mesenchymal stem cells (hMSC) and the antibacterial activity
      against gram-negative Escherichia coli and gram-positive Staphylococcus aureus
      were tested on the scaffolds. It was found that upon the addition of silver
      nanoparticles the porosity, pore size, swelling, and antibacterial properties
      were enhanced. The silver nanoparticles increased the in vitro enzyme degradation
      in samples without bioactive-glass; however, the degradation was remarkably
      reduced by addition of bioactive-glass. In addition, formation of apatite
      particles, the main inorganic constituent of the bone, on the surface of the
      bioactive-glass containing scaffolds were confirmed after immersion in simulated
      body fluid (SBF). The viability of hMSC on the scaffold suggested that
      gelatin/bioactive-glass/nanosilver scaffolds can be used as an antibacterial
      scaffolds.

PMID- 24749389
TI  - Oral mucosal immunization using glucomannosylated bilosomes.
AB  - The present study embarks on the feasibility of GM-bilosomes as a rationally
      designed vehicle for oral mucosal immunization. Bilosomes containing BSA as a
      model antigen were found to have vesicle size of 157 +/- 3 nm, PDI of 0.287 +/-
      0.045, zeta potential of -21.8 +/- 2.01 mV and entrapment efficiency of 71.3 +/-
      4.3%. Bilosomal formulations were freeze dried and entrapped BSA in freeze dried
      formulations was found to retain its structural and conformational stability as
      evident by SDS-PAGE and CD analysis. The GM-bilosomes were also found stable in
      different simulated biological fluids and bile salt solutions of different
      concentrations. In-vitro drug release revealed that GM-bilosomes were able to
      sustain drug release up to 24 h. In-vitro cell uptake in RAW 264.7 macrophage
      cells demonstrated significantly higher uptake of GM-bilosomes in comparison with
      bilosomes and free antigen. Intestinal uptake studies on excised rat intestinal
      sections further demonstrated higher uptake of vesicular systems throughout the
      intestinal region in comparison with free antigen. Significantly higher (p <
      0.05) systemic immune response (serum IgG level) was observed in case of GM
      bilosomes in comparison with bilosomes and alum adsorbed BSA (BSA-AL) following
      oral administration. The immune response observed in case of GM-bilosomes was
      comparable to BSA-AL administered through im route without any significant
      difference (p > 0.05). More importantly, GM-bilosomes were found capable of
      inducing mucosal immune response as well as cell mediated immune response which
      was not induced by im BSA-AL. In conclusion, GM-bilosomes could be considered as
      promising carrier and adjuvant system for oral mucosal immunization and
      productively exploited for oral delivery of other candidate antigens.

PMID- 24749390
TI  - Polymer-polymer conjugation to fabricate multi-block polymer as novel drug
      carriers: poly(lactic acid)-poly(ethylene glycol)-poly(L-lysine) to enhance
      paclitaxel target delivery.
AB  - Multifunctional nanoparticles assembled from multi-block polymers are now one of
      the most convenient and convincing carriers for target drug delivery. Multi-block
      polymers could provide multi-functions such as sufficient drug loading capability
      and efficient target ligand coupling potency. In this article, novel multi-block
      polymer poly(lactic acid)-poly(ethylene glycol)-poly(L-lysine) (PLA-PEG-PLL) with
      relatively precise block molecular weight were synthesized by new method which we
      called polymer-polymer conjugation. This method conjugated different polymer
      blocks by reactions between the terminal active groups of different blocks, thus
      simplified the synthesis procedure. The obtained PLA-PEG-PLL was characterized by
      1H NMR and gel permeation chromatography. The controlled drug delivery capability
      and the target ligand coupling potency of PLA-PEG-PLL were verified using
      paclitaxel (PTX) as model drug and vascular endothelial growth factor (VEGF)
      antibody as target ligand. The PTX-loaded PLA-PEG-PLL nanoparticles (PNP) and
      VEGF antibody modified PTX-loaded PLA-PEG-PLL nanoparticles (VPNP) were prepared
      using solvent diffusion methods. The two nanoparticles showed spherical or
      ellipsoidal shapes with uniform particle size distribution (190.1 +/- 1.27 nm and
      203.6 +/- 4.10 nm for PNP and VPNP, respectively) and positive zeta potential
      (23.76 +/- 0.72 mv and 20.76 +/- 0.34 mv for PNP and VPNP, respectively). The
      cellular cytotoxicity, cellular uptake, in vivo therapeutic effects of the two
      nanoparticles were investigated. Cytotoxicity of VPNP against HepG2 cells was
      superior to that of PNP and Taxol. The VPNP and PNP showed better antitumor
      efficacy in a murine model bearing H22 compared with Taxol and VPNP was the best.
      The study on cellular uptake indicated that the better antitumor efficacy of VPNP
      was attributed to the increased uptake of drug by tumor cells. These results
      demonstrated that PLA-PEG-PLL was a favorable multifunctional material for drug
      target delivery and polymer-polymer conjugation was a promising method to
      fabricate novel multi-block polymers.

PMID- 24749391
TI  - Bone regeneration induced by an in situ gel-forming poloxamine, bone
      morphogenetic protein-2 system.
AB  - The aim of this study was to confirm previously shown, in vitro osteogenic
      induction by the Tetronics T908 and T1307 in a critical-size, rat calvaria
      defect. In vivo, the osteogenic activity of the hydrogels was comparable to in
      vitro, but less pronounced. However, similar to in vitro, the system was strongly
      potentiated by incorporating 6.5 microg of bone morphogenetic protein-2 in
      solution or pre-encapsulated in poly(lactic-co-glycolic) acid microspheres. These
      two systems extended the in vivo release of bone morphogenetic protein-2,
      determined with 125I- bone morphogenetic protein-2, for one and two additional
      weeks, respectively, time enough to fill approximately 40% and 90% of the defect
      with well-organized bone. Furthermore, the structural characteristics of Tetronic
      hydrogels together with their biocompatibility, injectability, and adaptability
      to multiple defect sizes and shapes suggest their role as new, potential bone
      morphogenetic protein-2 delivery, low-cost scaffolds for minor as well as
      critical bone defects.

PMID- 24749392
TI  - Synthesis and characterization of diopside particles and their suitability along
      with chitosan matrix for bone tissue engineering in vitro and in vivo.
AB  - The scaffolds for bone tissue engineering should be porous to harbor the growth
      of new tissue ingrowths, biodegradable with no toxic end products, and
      biocompatible with no cytotoxicity. In this study we report that Diopside
      (CaMgSi2O6) (Dp) particles can be synthesized at a more economical route using
      the agricultural waste rice straw. Along with chitosan (CS) matrix, the CS/Dp
      scaffolds were synthesized and evaluated for their physico-chemical properties by
      SEM, EDS, XRD, FT-IR studies. Addition of Dp particles to chitosan matrix
      decreased water retention capacity but there was no change in their degradation
      properties. Dp particles in CS/Dp scaffolds exhibited good affinity for protein
      adsorption. Apatite forming ability of the CS/Dp scaffolds depicted their
      bioactivity. These scaffolds were found to be compatible with human osteoblastic
      cells (MG-63) and the cells were able to attach and proliferate with extended
      morphology on the CS/Dp membranes. The CS/Dp scaffolds supported up regulation of
      mRNA expression of osteoblast differentiation marker genes such alkaline
      phosphatase (ALP), type I collagen (COL-I) in the presence of osteogenic
      environment suggesting their osteo-conductive nature. In vivo rat model system
      identified that the CS/Dp scaffolds are biocompatible and may have the property
      of recruiting cells due to deposition of collagen. Hence, these studies suggest
      that the prepared CS/Dp scaffolds have potential applications towards bone tissue
      engineering.

PMID- 24749393
TI  - Gold nanoparticles enhanced electroporation for mammalian cell transfection.
AB  - Electroporation figured prominently as an effective nonviral gene delivery
      approach for its balance on the transfection efficiency and cell viability, no
      restrictions of probe or cell type, and operation simplicity. The commercial
      electroporation systems have been widely adopted in the past two decades while
      still carry drawbacks associated with the high applied electric voltage,
      unsatisfied delivery efficiency, and/or low cell viability. By adding highly
      conductive gold nanoparticles (AuNPs) in electroporation solution, we
      demonstrated enhanced electroporation performance (i.e., better DNA delivery
      efficiency and higher cell viability) on mammalian cells from two different
      aspects: the free, naked AuNPs reduce the resistance of the electroporation
      solution so that the local pulse strength on cells was enhanced; targeting AuNPs
      (e.g., Tf-AuNPs) were brought to the cell membrane to work as virtual
      microelectrodes to porate cells with limited area from many different sites. The
      enhancement was confirmed with leukemia cells in both a commercial batch
      electroporation system and a home-made flow-through system using pWizGFP plasmid
      DNA probes. Such enhancement depends on the size, concentration, and the mixing
      ratio of free AuNPs/Tf-AuNPs. An equivalent mixture of free AuNPs and Tf-AuNPs
      exhibited the best enhancement with the transfection efficiency increased 2-3
      folds at minimum sacrifice of cell viability. This new delivery concept, the
      combination of nanoparticles and electroporation technologies, may stimulate
      various in vitro and in vivo biomedical applications which rely on the efficient
      delivery of nucleic acids, anticancer drugs, or other therapeutic materials.

PMID- 24749394
TI  - Uptake mechanism and endosomal fate of drug-phospholipid lipid nanoparticles in
      subcutaneous and in situ hepatoma.
AB  - Drug-phospholipid lipid nanoparticles (DPLNs) can effectively enhance the
      properties of traditional solid lipid nanoparticles (SLNs) and nanostructured
      lipid carriers (NLCs), as previously demonstrated by our research group and
      others. To date, however, very few studies have focused on the cellular uptake
      mechanism and fate of DPLNs in hepatoma. Therefore, we systematically studied the
      cellular uptake mechanism and endosomal fate of DPLNs through in vitro and in
      vivo experiments. Confocal laser scanning microscopy (CLSM) and flow cytometry
      demonstrated that the Raw264.7 cell line (macrophage Raw264.7 cells), Chang cells
      (a human liver cell line) and HepG2 cells (a human hepatoma cell line) exhibited
      distinct uptake mechanisms. The Raw264.7 cells served as a model for examining
      liver-targeting ability. The results from mice with subcutaneous hepatomas and in
      situ hepatomas confirmed that the liver tumor-targeting property of the DPLNs was
      associated with the liver drug reservoir function. These findings further improve
      our understanding of DPLNs for clinical applications.

PMID- 24749395
TI  - Pegylation increases platelet biocompatibility of gold nanoparticles.
AB  - The increasing use of gold nanoparticles in medical diagnosis and treatment has
      raised the concern over their blood compatibility. The interactions of
      nanoparticles with blood components may lead to platelet aggregation and
      endothelial dysfunction. Therefore, medical applications of gold nanoparticles
      call for increased nanoparticle stability and biocompatibility. Functionalisation
      of nanoparticles with polythelene glycol (PEGylation) is known to modulate cell
      particle interactions. Therefore, the aim of the current study was to investigate
      the effects of PEGylated-gold nanoparticles on human platelet function and
      endothelial cells in vitro. Gold nanoparticles, 15 nm in diameter, were
      synthesised in water using sodium citrate as a reducing and stabilising agent.
      Functionalised polyethylene glycol-based thiol polymers were used to coat and
      stabilise pre-synthesised gold nanoparticles. The interaction of gold
      nanoparticles-citrate and PEGylated-gold nanoparticles with human platelets was
      measured by Quartz Crystal Microbalance with Dissipation. Platelet-nanoparticles
      interaction was imaged using phase-contrast, scanning and transmission electron
      microscopy. The inflammatory effects of gold nanoparticles-citrate and PEGylated
      gold nanoparticles in endothelial cells were measured by quantitative real time
      polymerase chain reaction. PEGylated-gold nanoparticles were stable under
      physiological conditions and PEGylated-gold nanoparticles-5400 and PEGylated-gold
      nanoparticles-10800 did not affect platelet aggregation as measured by Quartz
      Crystal Microbalance with Dissipation. In addition, PEGylated-gold nanoparticles
      did not induce an inflammatory response when incubated with endothelial cells.
      Therefore, this study shows that PEGylated-gold nanoparticles with a higher
      molecular weight of the polymer chain are both platelet- and endothelium
      compatible making them attractive candidates for biomedical applications.

PMID- 24749396
TI  - Tea nanoparticles for immunostimulation and chemo-drug delivery in cancer
      treatment.
AB  - Many health benefits have been associated with tea consumption. In an effort to
      elucidate the source of these health benefits, numerous phytochemicals have been
      extracted from tea infusions, some of which have demonstrated promise as clinical
      therapeutics for cancer therapy. Considering the advantageous properties of
      organic nanoparticles, the purpose of this study is to develop a method for
      isolating nanoparticles from tea leaves, and explore potential biomedical
      applications for these nanoparticles. First, an infusion-dialysis procedure for
      isolating tea nanoparticles (TNPs) from green tea infusions is developed. Second,
      atomic force microscopy and scanning electron microscopy reveal that the TNPs are
      spherical with diameters of 100-300 nm. Third, electrophoretic light scattering
      is used to determine that the TNPs have a zeta potential of -26.52 mV at pH 7.0.
      Finally, chemical analysis demonstrates that (-) Epigallocatechin gallate,
      caffeine, and theobromine are not found in the TNPs. Interestingly, the TNPs do
      enhance the in vitro secretion of cytokines IL-6, TNF-alpha, and G-CSF, as well
      as the chemokines RANTES, IP-10, MDC from mouse macrophages RAW264.7, indicating
      an immunostimulatory effect. As a nanocarrier, the TNPs are able to form
      complexes with doxorubicin (DOX) and have the potential for applications in drug
      delivery. Further the DOX-loaded TNPs increase the cellular DOX uptake, compared
      to free DOX, leading to higher cytotoxicity in the A549 human lung cancer and MCF
      7 breast cancer cells. More importantly, the DOX-loaded TNPs significantly
      increase the DOX uptake and cytotoxicity in MCF-7/ADR multidrug resistant breast
      cancer cells. In this work, an infusion-dialysis procedure is developed for
      isolation of the TNPs from green tea, and the potential of these nanoparticles as
      a multifunctional nanocarrier for cancer therapy in vitro is explored.

PMID- 24749397
TI  - Filopodial morphology correlates to the capture efficiency of primary T-cells on
      nanohole arrays.
AB  - Nanostructured surfaces emerge as a new class of material for capture and
      separation of cell populations including primary immune cells and disseminating
      rare tumor cells, but the underlying mechanism remains elusive. Although it has
      been speculated that nanoscale topological structures on cell surface are
      involved in the cell capture process, there are no studies that systematically
      analyze the relation between cell surface structures and the capture efficiency.
      Here we report on the first mechanistic study by quantifying the morphological
      parameters of cell surface nanoprotrusions, including filopodia, lamellipodia,
      and microvilli in the early stage of cell capture (< 20 min) in correlation to
      the efficiency of separating primary T lymphocytes. This was conducted by using a
      set of nanohole arrays (NHAs) with varying hole and pitch sizes. Our results
      showed that the formation of filopodia (e.g., width of filopodia and the average
      number of the filopodial filaments per cell) depends on the feature size of the
      nanostructures and the cell separation efficiency is strongly correlated to the
      number of filopodial fibers, suggesting a possible role of early stage
      mechanosensing and cell spreading in determining the efficiency of cell capture.
      In contrast, the length of filopodial filaments was less significantly correlated
      to the cell capture efficiency and the nanostructure dimensions of the NHAs. This
      is the first mechanistic study on nanostructure-based immune cell capture and
      provides new insights to not only the biology of cell-nanomaterial interaction
      but also the design of new rare cell capture technologies with improved
      efficiency and specificity.

PMID- 24749398
TI  - Biomedical imaging of colorectal cancer by near infrared fluorescent
      nanoparticles.
AB  - In this paper we describe the preparation of novel Near Infrared (NIR)
      fluorescent nanoparticles for application in medical imaging of colorectal
      tumors. The nanoparticles are prepared by using only non-covalent binding
      processes of molecules which are approved for clinical use. The preparation
      process is based on the precipitation of a polycation, Eudragit-RS, followed by
      sequential adsorption of a blocking protein, sodium caseinate, NIR fluorescent
      dye, Indocyanine Green (ICG) and optionally, a targeting molecule, anti-CEA
      antibody. Fluorescence measurements have shown that these nanoparticles have
      higher resistance to photobleaching and higher quantum yield relatively to free
      ICG. Imaging experiments in orthotopic colorectal cancer mice models have shown
      that these fluorescent nanoparticles are capable of binding to LS174T human colon
      tumors in vivo with high specificity, even without the targeting molecule. These
      nanoparticles, composed of all FDA approved materials, open the way to clinical
      bioimaging and diagnostics of colon cancer.

PMID- 24749399
TI  - Effect of nanostructure of mineralized collagen scaffolds on their physical
      properties and osteogenic potential.
AB  - Tissue engineering has enabled development of nanostructured collagen scaffolds
      to meet current challenges in regeneration of lost bone. In this study,
      extrafibrillarly-mineralized and intrafibrillarly-mineralized collagen scaffolds
      were fabricated separately by a conventional crystallization method and a
      biomimetic, bottom-up crystallization method. Atomic force microscopy (AFM) was
      employed to examine the nanotopography and nanomechanics of the mineralized
      collagen scaffolds. The in vitro cell responses to the surface of the mineralized
      collagen scaffolds were analyzed by laser scanning microscope and field emission
      scanning electron microscopy. AFM imaging showed that these two mineralized
      collagen scaffolds exhibited different nanostructure, including the size,
      morphology and location of the apatites in collagen fibrils. The nanomechanical
      testing demonstrated that the intrafibrillarly-mineralized collagen scaffold,
      with bone-like hierarchy, featured a significantly increased Young's modulus
      compared with the extrafibrillarly-mineralized collagen scaffold in both dry and
      wet conditions. However, these two mineralized collagen scaffolds had a similar
      thermal behavior. From the cell culture experiments, the intrafibrillarly
      mineralized collagen scaffold showed higher cell proliferation and alkaline
      phosphatase activity than the extrafibrillarly-mineralized collagen scaffold. The
      utmost significance of this study is that the nanostructure of the mineralized
      collagen scaffolds can affect the initial cell adhesion, morphology and further
      osteogenic potential. The present study will help us to fabricate novel
      biomaterials for bone grafting and tissue engineering applications.

PMID- 24749400
TI  - Nanostructured hybrid of immiscible gold and silicon and its effect on
      proliferation and adhesion of fibroblasts and osteoblasts.
AB  - Hybrid biomaterials are a combination of two or more different materials that
      work synergistically to produce superior properties. Nano structuring of such
      hybrid materials has also posed complications. In this study, we present, for the
      first time a nanofibrous hybrid of gold and silicon fabricated by femtosecond
      laser synthesis for tissue engineering applications. The formation of a
      completely new phase, Au3Si (212) is reported. The formation mechanism is
      explained by vapor condensation. Particle sizes of 2-10 nm and 37-49 nm for gold
      and gold concentrations of 35-78% are achieved. The effect of this hybrid on cell
      growth was assessed using fibroblasts and osteoblasts. There was a significant
      decrease in both osteoblast and fibroblast proliferation with the increase of
      gold in the hybrid nanostructure. This novel hybrid nanofibrous matrix provides a
      method to effectively control the proliferation and adhesion of cells.
      Femtosecond laser synthesis presents a new standard by which not only a single
      element biomaterial but also multiple immiscible element hybrid biomaterials can
      be fabricated. This technique provides a paradigm shift in the fabrication of
      novel nanostructured immiscible hybrid biomaterials.

PMID- 24749401
TI  - Enhanced cellular uptake and biodistribution of a synthetic cannabinoid loaded in
      surface-modified poly(lactic-co-glycolic acid) nanoparticles.
AB  - This article aimed to produce, characterize and evaluate different surface
      modified naphthalen-1-yl-(4-pentyloxynaphthalen-1-yl)methanone (CB13) loaded
      poly(lactic-co-glycolic acid) nanoparticles in order to improve their oral
      absorption and in vivo biodistribution. Plain and surface-modified PLGA
      nanoparticles were successfully prepared using a nanoprecipitation method.
      Chitosan, Eudragit RS, lecithin and vitamin E were used as surface modifying
      agents. The NPs were evaluated in terms of mean diameter and size distribution,
      zeta potential, morphology, drug loading, drug release profiles, mucoadhesive
      properties, in vitro cell viability and uptake and in vivo biodistribution. Mean
      particle size distributions in the range of 253-344 nm, spherical shape and
      controlled zeta potential values were observed depending on the additive
      employed. High values of entrapment efficiency were obtained for all the
      formulations. Lecithin and vitamin E modified particles showed higher release
      rates when compared to the rest of formulations. A clear improvement in ex vivo
      mucoadhesion properties was observed in the case of chitosan- and Eudragit RS
      modified nanoparticles. Chitosan-poly(lactic-co-glycolic acid) nanoparticles
      showed the highest uptake values on Caco-2 cells. Biodistribution assays proved
      that most of the particles were accumulated in liver and spleen. An important
      goal has been achieved in this investigation: CB13, a highly lipophilic drug with
      low water solubility, can reach the interior of cells more efficiently when it is
      included in these surface-modified polymeric carriers.

PMID- 24749402
TI  - The effect of alendronate-loaded polycarprolactone nanofibrous scaffolds on
      osteogenic differentiation of adipose-derived stem cells in bone tissue
      regeneration.
AB  - The osteogenic effect of culturing adipose-derived stem cells (ADSCs) on
      alendronate (Aln)-loaded polycarprolactone (PCL) nanofibrous scaffolds was
      evaluated by examining alkaline phosphatase (ALP) activity, calcium content, and
      expression of osteogenic differentiation genes in vitro. The 10% Aln/PCL
      nanofibrous scaffolds showed more ALP activity, mineralization, and osteocalcin
      and osteopontin mRNA than the 1% or 5% Aln/PCL nanofibrous scaffolds. The
      capacity of Aln/PCL nanofibrous scaffolds to regenerate new bone was studied in a
      rat calvarial defect model. New bone formation in vivo was evaluated by
      radiography, micro-computed tomography, and histological analysis. At 8 weeks
      after implantation, Aln/PCL scaffolds had a positive effect on bone regeneration
      and matrix formation. These results suggested that Aln/PCL nanofibrous scaffolds
      enhanced the osteogenic differentiation of ADSCs in vitro and bone formation in
      vivo.

PMID- 24749403
TI  - Biocompatibility and bone-repairing effects: comparison between porous poly
      lactic-co-glycolic acid and nano-hydroxyapatite/poly(lactic acid) scaffolds.
AB  - Copolymer composite scaffolds and bioceramic/polymer composite scaffolds are two
      representative forms of composite scaffolds used for bone tissue engineering.
      Studies to compare biocompatibility and bone-repairing effects between these two
      scaffolds are significant for selecting or improving the scaffold for clinical
      application. We prepared two porous scaffolds comprising poly-lactic-acid/poly
      glycolic-acid (PLGA) and poly-lactic-acid/nano-hydroxyapatite (nHAP/PLA)
      respectively, and examined their biocompatibility with human bone marrow-derived
      mesenchymal stem cells (hMSCs) through evaluating adhesion, proliferation and
      osteogenic differentiation potentials of hMSCs in the scaffold. Then, the PLGA
      scaffold with hMSCs (PM construct) and the nHAP/PLA scaffold with hMSCs (HPM
      construct) were transplanted into the rat calvarial defect areas to compare their
      effects on the bone reconstruction. The results showed that the nHAP/PLA scaffold
      was in favor of adhesion, matrix deposition and osteogenic differentiation of
      hMSCs. For in vivo transplantation, both HPM and PM constructs led to
      mineralization and osteogenesis in the defect area of rat. However, the area
      grafted with PM construct showed a better formation of mature bone than that with
      HPM construct. In addition, the evaluation of in vitro and in vivo degradation
      indicated that the degradation rate of nHAP/PLA scaffold was much lower than that
      of PLGA scaffold. It is inferred that the lower degradation of nHAP/PLA scaffold
      should result in its inferior bone reconstruction in rat calvaria. Therefore, the
      preparation of an ideal composite scaffold for bone tissue engineering should be
      taken into account of the balance between its biocompatibility, degradation rate,
      osteoconductivity and mechanical property.

PMID- 24749404
TI  - Bi-layer scaffold of chitosan/PCL-nanofibrous mat and PLLA-microporous disc for
      skin tissue engineering.
AB  - Current treatments for severe skin damage involve the grafting of extremely
      limited autogenic skin or the use of synthetic skin grafts that do not fully
      recapitulate the biological properties of native skin. In this study we developed
      a novel bi-layer scaffold that provides the microenvironmental cues favorable to
      promoting skin healing and regeneration. The scaffold is composed of a
      superficial chitosan/PCL nanofibrous mat (CP-nano mat) and an underlying PLLA
      microporous disc (PLLA-micro disc). The porous structure of the scaffold permits
      the interaction of biomolecules released from two types of cells distributed,
      respectively, throughout the two layers of the scaffold, but the nanofibers
      prevent the direct intermingling of the cell types. The CP-nano mat and PLLA
      micro disc were fabricated by electrospinning and thermally induced phase
      separation, respectively, and host keratinoctyes as an epidermal equivalent and
      fibroblasts as a dermal equivalent, respectively, present in the native skin. The
      potential of this bi-layer scaffold to serve as a skin equivalent was evaluated
      by co-culture of keratinocytes and fibroblasts and subsequent assessment of cell
      proliferation, cell morphology, gene transcription, and protein expression. The
      cell proliferation was found to be greatest in co-culture on bi-layer scaffolds.
      The gene and protein expression analyses further confirmed that the bi-layer
      scaffold provided a micro-environment similar to those present in the native
      extracellular matrix during initial wound healing. Our study suggested that the
      bi-layer scaffold has great potential to serve as a skin equivalent in tissue
      engineering.

PMID- 24749406
TI  - One-step assay for optical prostate specific antigen detection using magnetically
      engineered responsive thin film.
AB  - We report a novel and very simple method for the detection of proteolytically
      active prostate specific antigen (PSA) at a very low concentration using a self
      assembled monolayer (SAM) of magnetic beads conjugated with peptide. The
      application of surface plasmon resonance (SPR) allows real-time optical
      characterization of the constructed recognition monolayer. This set-up is also
      capable of rapid monitoring of PSA samples through an instantaneous detection of
      medium refractive index shift induced by the enzymatic cleavage of the peptide
      and the dissociation of free magnetic beads. The results showed the ability of
      our SPR sensor to detect PSA within a short time (few minutes to 30 min) with
      high sensitivity (100 pg/ml) and specificity. Thanks to the elimination of
      washing and blocking steps, as well as the signal amplification and labeling
      procedures, this approach can be implemented in other miniaturized configurations
      such as screen printed electrode and biochip array amenable to low-cost point-of
      care devices.

PMID- 24749405
TI  - Design of nanodrugs for miRNA targeting in tumor cells.
AB  - The delivery of oligonucleotide antagonists to cytosolic RNA targets such as
      microRNA represents an avenue for the post-transcriptional control of cellular
      phenotype. In tumor cells, oncogenic miRNAs, termed oncomirs, are tightly linked
      to processes that ultimately determine cancer initiation, progression, and
      response to therapy. Therefore, the capacity to redirect tumor cell fate towards
      therapeutically beneficial phenotypes holds promise in a future clinical
      scenario. Previously, we have designed "nanodrugs" for the specific inhibition of
      oncogenic microRNAs in tumor cells. The basic design of these nanodrugs includes
      dextran coated iron oxide nanoparticles, conjugated to a tumor-targeting peptide,
      and a locked nucleic acid (LNA)-modified antisense oligonucleotide that stably
      binds and inhibits the complementary mature miRNA. Here, we focus on elucidating
      an optimal nanodrug design for effective miRNA inhibition in tumor cells.
      Specifically, we investigate the choice of chemical linker for the conjugation of
      the oligonucleotide to the nanoparticles and evaluate the contribution of tumor
      cell targeting to nanodrug uptake and functionality. We find that short labile
      linkers (SPDP; N-Succinimidyl 3-(2-pyridyldithio)-propionate) are superior to non
      labile short linkers (GMBS; N-(gamma-Maleimidobutyryloxy)succinimide ester) or
      non-labile long linkers (PEG24; Succinimidyl-([N-maleimidopropionamido]
      24ethyleneglycol)ester) in terms of their capacity to gain access to the
      cytosolic cellular compartment and to engage their cognate miRNA. Furthermore,
      using the nanodrug design that incorporates SPDP as a linker, we establish that
      the addition of tumor-cell targeting through functionalization of the nanodrug
      with the alphavbeta3-specific cyclic RGDfK-PEG peptide does not confer an
      advantage in vitro at long incubation times required for inhibition.

PMID- 24749407
TI  - Cationic nanostructured polymers for siRNA delivery in murine calvarial pre
      osteoblasts.
AB  - The endogenous RNA interference (RNAi) pathway enables control of pathologies
      caused by the dysregulation of proteins. Several biological molecules are active
      in RNAi including short interfering ribonucleic acid (siRNA). The effective
      utilization of siRNA as a therapeutic agent has been marked with distinct
      challenges, namely in intracellular delivery and achieving a sufficient dosage to
      affect protein expression. A delivery strategy we have developed to improve
      safety and efficacy of siRNA includes complexing siRNA with nanostructured
      polymers delivery systems (NSPs). These NSPs are synthesized via atom transfer
      radical polymerization (ATRP) and combine several important advances in polymer
      architecture for siRNA delivery. This includes shielding the cationic charge of
      the NSP with a poly(ethylene glycol) (PEG) shell to promote cell viability in
      MC3T3-E1.4 pre-osteoblasts, and minimize the inflammatory response in a C57BL/6
      mouse model. In our gene knockdown experiments targeting glyceraldehyde 3
      phosphate dehydrogenase Gapdh expression, star polymer and nanogel polyplexes
      suppressed Gapdh mRNA to levels comparable to cells treated with Lipofectamine
      RNAiMAX lipoplexes.

PMID- 24749408
TI  - Nanoencapsulation of olanzapine increases its efficacy in antipsychotic treatment
      and reduces adverse effects.
AB  - Olanzapine is an atypical antipsychotic drug, whose chronic use has been
      associated with the development of potential adverse effects such as weight gain
      and cardio-metabolic disorders like hypercholesterolemia and diabetes. To
      circumvent these side effects, the controlled release of olanzapine is a
      promising approach to improve adhesion of schizophrenic patients to the
      treatment. An innovative strategy to prolong drug release consists of loading the
      drug into biodegradable polymeric lipid-core nanocapsules. In this study,
      particle size, polydispersity, pH, zeta potential and drug loading of olanzapine
      loaded lipid-core nanocapsules were analyzed. Weight gain, biochemical parameters
      and antipsychotic activity were evaluated in male Wistar rats. The lipid-core
      nanocapsules had a mean diameter of 156 +/- 13 nm, a polydispersity index lower
      than 0.1, a pH value of 6.12 +/- 0.14, zeta potential of -17 +/- 2.40 mV and
      encapsulation efficiency close to 100%. The animals treated with olanzapine
      loaded lipid-core nanocapsules showed significantly lower weight gain (63.4 +/-
      19.6 g) and total cholesterol levels (66.2 +/- 3.5 g x dl(-1)), compared to those
      administered with free olanzapine (112.6 +/- 10.3 g and 90.4 +/- 2.4 g x dl(-1)),
      respectively. Additionally, a more prolonged antipsychotic action was observed in
      the stereotyped behavior animal model induced by D,L-amphetamine, which affords
      to conclude that nanoencapsulation is a promising alternative to treat
      schizophrenic patients.

PMID- 24749409
TI  - Impact of silver nanoparticles and silver ions on innate immune cells.
AB  - Silver is commonly used as an antibacterial agent, e.g., in various medical
      applications, and the availability of silver nanoparticles (AgNP) has fueled this
      development. Their antibacterial properties are well defined, whereas there are
      concerns regarding unknown and potentially harmful effects of AgNPs on immune
      cells and an ongoing immune reaction. Aim of the present study is a comparison of
      the effects of AgNPs and ionic silver (Ag+) on cells of the innate immune system,
      in particular on neutrophil granulocytes and macrophages. The AgNPs were
      synthesized within hydroxylated polyester dendrimer templates via an in situ
      approach, generating five kinds of AgNPs with mean diameters from 2.0 to 34.7
      nm.4 No impact is observed on phagocytosis and oxidative burst, as well as
      activation of the promoter for the pro-inflammatory cytokine TNF-alpha. In
      contrast, both AgNPs and Ag+, but not the dendrimer templates, trigger the
      release of neutrophil extracellular traps and inhibit the formation of nitric
      monoxide. On the molecular level, AgNPs and Ag+ cause elevated intracellular
      levels of reactive oxygen species and the second messenger Zn2+. Moreover,
      protein phosphatases are inhibited by an oxidative mechanism. Taken together,
      there are several effects of AgNPs on neutrophil granulocytes and macrophages in
      vitro, but these are not specific for AgNP, instead they are also observed with
      Ag+, and Ag+ released from AgNPs seems to be the component responsible for most
      of the particles' immunomodulatory activity.

PMID- 24749410
TI  - White organic light-emitting diodes with Zn-complexes.
AB  - This paper reviews OLEDs fabricated using Zn-complexes. Zn(HPB)2, Zn(HPB)q, and
      Zn(phen)q were synthesized as new electroluminescence materials. The electron
      affinity (EA) and ionization potential (IP) of Zn complexes were also determined
      and devices were characterized. Zn complexes such as Zn(HPB)2, Zn(HPB)q, and
      Zn(phen)q were found to exhibit blue and yellow emissions with wavelengths of
      455, 532, and 535 nm, respectively. On the other hand, Zn(HPB)2 and Zn(HPB)q were
      applied as hole-blocking materials. As a result, the OLED efficiency by using
      Zn(HPB)2 as a hole-blocking material was improved. In particular, the OLED
      property of Zn(HPB)2 was found to be better than that of Zn(HPB)q. Moreover,
      Zn(phen)q was used as an electron-transporting material and compared with Alq3.
      The performance of the device with Zn(phen)q as an electron-transporting material
      was improved compared with Alq3-based devices. The Zn complexes can possibly be
      used as hole-blocking and electron-transporting materials in OLED devices. A
      white emission was ultimately realized from the OLED devices using Zn-complexes
      as inter-layer components.

PMID- 24749411
TI  - Poly(3-hexylthiophene) nanostructured materials for organic electronics
      applications.
AB  - Semiconducting polymers have been developed during the last few decades and are
      currently used in various organic electronics applications. Regioregular poly(3
      hexylthiophene) (P3HT) is the most employed semiconducting polymer for organic
      electronics applications. The development of living Grignard metathesis
      polymerization (GRIM) allowed the synthesis of P3HT with well-defined molecular
      weights and functional end groups. A large number of block copolymers containing
      P3HT have been reported, and their opto-electronic properties have been
      investigated. The performance of P3HT homopolymer and block copolymers in field
      effect transistors and bulk heterojunction solar cells are discussed in this
      review. The morphology of the P3HT materials is also discussed.

PMID- 24749412
TI  - Highly efficient multiple-layer CdS quantum dot sensitized III-V solar cells.
AB  - In this review, the concept of utilization of solar spectrum in order to increase
      the solar cell efficiency is discussed. Among the three mechanisms, down-shifting
      effect is investigated in detail. Organic dye, rare-earth minerals and quantum
      dots are three most popular down-shift materials. While the enhancement of solar
      cell efficiency was not clearly observed in the past, the advances in quantum dot
      fabrication have brought strong response out of the hybrid platform of a quantum
      dot solar cell. A multiple layer structure, including PDMS as the isolation
      layer, is proposed and demonstrated. With the help of pulse spray system, precise
      control can be achieved and the optimized concentration can be found.

PMID- 24749413
TI  - Fullerene derivatives as electron acceptors for organic photovoltaic cells.
AB  - Energy is currently one of the most important problems humankind faces. Depletion
      of traditional energy sources such as coal and oil results in the need to develop
      new ways to create, transport, and store electricity. In this regard, the sun,
      which can be considered as a giant nuclear fusion reactor, represents the most
      powerful source of energy available in our solar system. For photovoltaic cells
      to gain widespread acceptance as a source of clean and renewable energy, the cost
      per watt of solar energy must be decreased. Organic photovoltaic cells, developed
      in the past two decades, have potential as alternatives to traditional inorganic
      semiconductor photovoltaic cells, which suffer from high environmental pollution
      and energy consumption during production. Organic photovoltaic cells are composed
      of a blended film of a conjugated-polymer donor and a soluble fullerene
      derivative acceptor sandwiched between a poly(3,4
      ethylenedioxythiophene):poly(styrenesulfonate)-coated indium tin oxide positive
      electrode and a low-work-function metal negative electrode. Considerable research
      efforts aim at designing and synthesizing novel fullerene derivatives as electron
      acceptors with up-raised lowest unoccupied molecular orbital energy, better light
      harvesting properties, higher electron mobility, and better miscibility with the
      polymer donor for improving the power conversion efficiency of the organic
      photovoltaic cells. In this paper, we systematically review novel fullerene
      acceptors synthesized through chemical modification for enhancing the
      photovoltaic performance by increasing open-circuit voltage, short-circuit
      current, and fill factor, which determine the performance of organic photovoltaic
      cells.

PMID- 24749414
TI  - Anatase TiO2 nanotubes as photoanode for dye-sensitized solar cells.
AB  - To achieve higher power conversion efficiency of dye-sensitized solar cells,
      anatase TiO2 nanotubes anodized and transferred onto fluorine doped tin oxide
      glass. This technique is a promising candidate to improve the efficiency due to
      its outstanding properties, such as high light scattering effect, high surface-to
      volume ratio, which result in enhancing light harvesting, minimum trapping sites,
      and low recombination rate. In this review, the structure, fabrication, and
      property of the TiO2 nanotube photoanode is compared with other photoanodes. In
      addition, the integration of a heterojunction and other advancements into the
      TiO2 nanotubes for getting better performance is also briefly discussed.

PMID- 24749415
TI  - Surface plasmonic effects on organic solar cells.
AB  - Most high-performance organic photovoltaic (OPV) devices reported in the
      literature have been fabricated using the bulk heterojunction (BHJ) concept.
      Typically, the optimum thickness of the active layer for an OPV device is around
      100 nm, or possibly less; such a thin layer can lead to low absorption of light.
      A thicker layer, however, inevitably increases the device resistance, due to the
      low carrier mobilities and short exciton diffusion lengths in organic materials.
      This situation imposes a trade-off between light absorption and charge transport
      efficiencies in OPV devices, motivating the development of a variety of light
      trapping techniques. Metallic nanoparticles (NPs) such as Ag, Au, etc. and other
      metallic nanostructures are potential candidates for improving the light
      absorption due to the localized surface plasmon resonance (LSPR). LSPR
      contributes to the significant enhancement of local electromagnetic fields and
      improves the optical properties of the nanostructure devices. The excitation of
      LSPR is achieved when the frequency of the incident light matches its resonance
      peak, resulting in unique optical properties; selective light extinction as well
      as local enhancement of electromagnetic fields near the surface of metallic NPs.
      The resonance peak of LSPR depends strongly on the size, shape, and the
      dielectric environment of the metallic NPs. In this review article, progress on
      plasmonic enhanced OPV device performance is examined. The concepts of surface
      plasmonics for OPV devices, suitable plasmonic materials, location, optimum size
      and concentration of NP materials within the device are explored.

PMID- 24749416
TI  - Graphene doping methods and device applications.
AB  - Graphene has recently been studied as a promising material to replace and enhance
      conventional electronic materials in various fields such as electronics,
      photovoltaics, sensors, etc. However, for the electronic applications of graphene
      prepared by various techniques such as chemical vapor deposition, chemical
      exfoliation, mechanical exfoliation, etc., critical limitations are found due to
      the defects in the graphene in addition to the absence of a semiconducting band
      gap. For that, many researchers have investigated the doped graphene which is
      effective to tailor its electronic property and chemical reactivity. This work
      presents a review of the various graphene doping methods and their device
      applications. As doping methods, direct synthesis method and post treatment
      method could be categorized. Because the latter case has been widely investigated
      and used in various electronic applications, we will focus on the post treatment
      method. Post treatment method could be further classified into wet and dry doping
      methods. In the case of wet doping, acid treatment, metal chloride, and organic
      material coating are the methods used to functionalize graphene by using dip
      coating, spin coating, etc. Electron charge transfer achieved from graphene to
      dopants or from dopants to graphene makes p-type or n-type graphenes,
      respectively, with sheet resistance reduction effect. In the case of dry doping,
      it can be further categorized into electrostatic field method, evaporation
      method, thermal treatment method, plasma treatment method, etc. These doping
      techniques modify Fermi energy level of graphene and functionalize the property
      of graphene. Finally, some perspectives and device applications of doped graphene
      are also briefly discussed.

PMID- 24749417
TI  - Nitrogen-doped graphene materials for supercapacitor applications.
AB  - Development of advanced functional materials for energy conversion and storage
      technologies play a key role in solving the problems of the rapid depletion of
      fossil fuels and increasingly worsened environmental pollution caused by vast
      fossil-fuel consumption. Supercapacitors (SCs), also known as ultracapacitors,
      which store energy based on either ion adsorption or fast/reversible faradaic
      reactions, are supposed to be a promising candidate for alternative energy
      storage devices due to their high rate capability, pulse power supply, long cycle
      life, simple principles, high dynamics of charge propagation, and low maintenance
      cost. The performance of supercapacitors highly depends on the properties of
      electrode materials. Nitrogen-doped graphene (NG)-based materials exhibit great
      potential for application in supercapacitors because of their unique structure
      and excellent intrinsic physical properties, such as large surface area with
      appropriate pore structure, controllable two- or three-dimensional morphology,
      and extraordinarily electrical conductivity. In this review, we provide a brief
      summary of recent research progress on NG-based electrode materials for SCs,
      including the various synthesis methods and the mechanisms of electrochemical
      performance enhancement.

PMID- 24749418
TI  - Graphene-based multilayers constructed from layer-by-layer self-assembly
      techniques.
AB  - This paper reviews the recent research and development of graphene-based
      multilayers fabricated from layer-by-layer (LBL) self-assembly technique.
      Graphene multilayer films, due to their excellent performances and specific
      applications, have attracted widespread attention during recent decades. In this
      paper, the preparation and property of self-assembled graphene multilayer films
      are introduced. The application of different graphene multilayer films in
      transparent conducting films (TCFs), field effect transistors (FETs), lithium ion
      batteries (LIBs), supercapacitors, and solar cells are summarized and discussed.
      The perspectives for the future developments of self-assembled graphene
      multilayer films are proposed.

PMID- 24749419
TI  - Polymer composites with graphene nanofillers: electrical properties and
      applications.
AB  - Graphene with extraordinary high elastic modulus and excellent electrical
      conductivity has good prospects for use as the filler material for fabricating
      novel polymer composites designed for electrostatic discharge and EMI shielding
      protection, field emission, gas sensor, and fuel cell applications. Large amounts
      of graphene oxide (GO) can be obtained by wet chemical oxidation of graphite into
      a mixture of concentrated sulfuric acid, sodium nitrate and potassium
      permanganate. Accordingly, carbon atoms in the basal plane and edges of GO are
      decorated with oxygenated functional groups, forming an electrical insulator. To
      restore electrical conductivity, chemical reduction or thermal annealing is
      needed to eliminate oxygenated groups of GO. However, such treatments induce
      internal defects and remove oxygenated atoms of GO partially. The remnant
      oxygenated groups affect electrical conductivity of graphene greatly.
      Nevertheless, reduced graphene oxide and thermally reduced graphene oxide are
      sufficiently conductive to form polymer nanocomposites at very low percolation
      threshold. This review provides the fundamentals and state-of-the-art
      developments in the fabrication methods and electrical property characterizations
      as well as the applications of novel graphene/polymer nanocomposites. Particular
      attention is paid to their processing-structural-electrical property
      relationships.

PMID- 24749420
TI  - Nanoceramic oxide hybrid electrolyte membranes for proton exchange membrane fuel
      cells.
AB  - This review reports on the functions and applications of nanoceramic oxides in
      proton exchange membrane fuel cells (PEMFCs). Such materials are mainly used as
      fillers to enhance the water uptake and proton conductivity of polymeric matrices
      at high temperatures under low relative humidity. To further enhance the
      mechanical property of proton exchange membranes (PEMs), the functionalized
      ceramic oxides with organic groups are introduced. Furthermore, the inorganic
      PEMs are developed to improve their proton conductivities at elevated
      temperatures. Due to the inherent disadvantages of polymeric PEMs, it is believed
      that the inorganic PEMs based on porous ceramic oxides are a promising new
      candidate as solid electrolyte membranes in PEMFCs at high temperatures and with
      low relative humidity.

PMID- 24749421
TI  - Nanostructure-based proton exchange membrane for fuel cell applications at high
      temperature.
AB  - As a clean and highly efficient energy source, the proton exchange membrane fuel
      cell (PEMFC) has been considered an ideal alternative to traditional fossil
      energy sources. Great efforts have been devoted to realizing the
      commercialization of the PEMFC in the past decade. To eliminate some technical
      problems that are associated with the low-temperature operation (such as catalyst
      poisoning and poor water management), PEMFCs are usually operated at elevated
      temperatures (e.g., > 100 degrees C). However, traditional proton exchange
      membrane (PEM) shows poor performance at elevated temperature. To achieve a high
      performance PEM for high temperature fuel cell applications, novel PEMs, which
      are based on nanostructures, have been developed recently. In this review, we
      discuss and summarize the methods for fabricating the nanostructure-based PEMs
      for PEMFC operated at elevated temperatures and the high temperature performance
      of these PEMs. We also give an outlook on the rational design and development of
      the nanostructure-based PEMs.

PMID- 24749422
TI  - Controlled synthesis of porous platinum nanostructures for catalytic
      applications.
AB  - Porous platinum, that has outstanding catalytic and electrical properties and
      superior resistant characteristics to corrosion, has been widely applied in
      chemical, petrochemical, pharmaceutical, electronic, and automotive industries.
      As the catalytic activity and selectivity depend on the size, shape and structure
      of nanomaterials, the strategies for controlling these factors of platinum
      nanomaterials to get excellent catalytic properties are discussed. Here, recent
      advances in the design and preparation of various porous platinum nanostructures
      are reviewed, including wet-chemical synthesis, electro-deposition, galvanic
      replacement reaction and de-alloying technology. The applications of various
      platinum nanostructures are also discussed, especially in fuel cells.

PMID- 24749423
TI  - Exchange bias effect in nanostructured magnetic oxides.
AB  - The exchange bias phenomenon observed in nanostructured magnetic oxides with the
      combination of a variety of magnetic phases such as ferromagnetic,
      antiferromagnetic, ferrimagnetic, cluster glass, spin glass and disordered
      magnetic state are reviewed. The systems of different types of magnetic oxides
      are investigated here. The exchange bias phenomenon has been discussed based on
      macroscopic experimental tools such as magnetization and magnetoresistance
      measurements. Some of the applications are also discussed. Some of the factors
      controlling exchange bias phenomenon and some unsolved issues are also
      highlighted.

PMID- 24749424
TI  - Non-biofouling polymeric thin films on solid substrates.
AB  - Nanoarchitectured polymer thin films are playing an increasingly pivotal role in
      a wide range of areas such as interfacial reactions, biomedical devices/implants,
      biosensors, food packing, and marine equipment. This review highlights recent
      research results in the field of the non-biofouling polymer films, including
      current understanding of the mechanisms of non-biofouling efficacy against
      bioentities (for example, proteins, cells, and bacteria) under different
      biological conditions. We also discuss current advances in the fabrication of non
      biofouling coatings and micropatterns of cells on solid substrates and suggest a
      guideline when designing a non-biofouling polymer films, according to application
      requirements.

PMID- 24749425
TI  - From clusters to semiconductor nanostructures.
AB  - In the last two decades there has been tremendous interest in various aspects of
      nanoscience and nanotechnology. Now the subject has matured into an important
      field in the general area of science and technology that has been identified as
      one of the thrust areas. Nanoscience and nanotechnology is really an
      interdisciplinary and/or multidisciplinary subject. This review describes work on
      transition metal molecular level clusters. The clusters were fabricated by making
      very dilute solutions and also by doping them in lattices of alkali halides and
      alkali cyanides. Size dependence of the bandgap was shown for the first time by
      using site-selective dye laser spectroscopy, time resolved spectroscopy, optical
      absorption and molecular orbital calculations. A number of semiconductor
      nanostructures such as quantum wires, quantum wells, and coupled quantum wells,
      and many-body effects in nanostructures such as self-assembled quantum dots,
      exciton-phonon interactions, four wave mixing, polymer composites, metallic
      nanoparticles and metal oxides are discussed.

PMID- 24749426
TI  - Fabrication of one-dimensional organic nanomaterials and their optoelectronic
      applications.
AB  - This paper reviews the recent research and development of one-dimensional (1D)
      organic nanomaterials synthesized from organic semiconductors or conducting
      polymers and their applications to optoelectronics. We introduce synthetic
      methodologies for the fabrication of 1D single-crystalline organic nanomaterials
      and 1D multi-component organic nanostructures, and discuss their optical and
      electrical properties. In addition, their versatile applications in
      optoelectronics are highlighted. The fabrication of highly crystalline organic
      nanomaterials combined with their integration into nanoelectronic devices is
      recognized as one of the most promising strategies to enhance charge transport
      properties and achieve device miniaturization. In the last part of this review,
      we discuss the challenges and the perspectives of organic nanomaterials for
      applications in the next generation soft electronics, in terms of fabrication,
      processing, device integration, and investigation on the fundamental mechanisms
      governing the charge transport behaviors of these advanced materials.

PMID- 24749427
TI  - Roll-to-roll gravure with nanomaterials for printing smart packaging.
AB  - Roll-to-roll (R2R) gravure is considered one of the highest throughput tools for
      manufacturing inexpensive and flexible ubiquitous IT devices called "smart
      packaging" in which NFC (near-field communication) transponder, sensors, ADC
      (analog-to-digital converter), simple processor and signage are all integrated on
      paper or plastic foils. In this review, we show R2R gravure can be employed to
      print smart packaging, starting from printing simple electrodes, dielectrics,
      capacitors, diodes and thin film transistors with appropriate nanomaterial-based
      inks on plastic foils.

PMID- 24749428
TI  - Advances in fractal germanium micro/nanoclusters induced by gold: microstructures
      and properties.
AB  - Germanium materials are a class of unique semiconductor materials with widespread
      technological applications because of their valuable semiconducting, electrical,
      optical, and thermoelectric power properties in the fields of macro/mesoscopic
      materials and micro/nanodevices. In this review, we describe the efforts toward
      understanding the microstructures and various properties of the fractal germanium
      micro/nanoclusters induced by gold prepared by high vacuum thermal evaporation
      techniques, highlighting contributions from our laboratory. First, we present the
      integer and non-integer dimensional germanium micro/nanoclusters such as
      nanoparticles, nanorings, and nanofractals induced by gold and annealing. In
      particular, the nonlinear electrical behavior of a gold/germanium bilayer film
      with the interesting nanofractal is discussed in detail. In addition, the third
      order optical nonlinearities of the fractal germanium nanocrystals embedded in
      gold matrix will be summarized by using the sensitive and reliable Z-scan
      techniques aimed to determine the nonlinear absorption coefficient and nonlinear
      refractive index. Finally, we emphasize the thermoelectric power properties of
      the gold/germanium bilayer films. The thermoelectric power measurement is
      considered to be a more effective method than the conductivity for investigating
      superlocalization in a percolating system. This research may provide a novel
      insight to modulate their competent performance and promote rational design of
      micro/nanodevices. Once mastered, germanium thin films with a variety of
      fascinating micro/nanoclusters will offer vast and unforeseen opportunities in
      the semiconductor industry as well as in other fields of science and technology.

PMID- 24749429
TI  - Synthesis of nanomaterials by continuous-flow microfluidics: a review.
AB  - The development of controlled synthesis protocols of nanostructured materials
      with tailored particle size and shape has been a significant research area in
      nanoscience and nanotechnology. Much innovative research efforts had been focused
      on finding suitable chemical reagents and synthetic methodologies that offer
      opportunities to produce the desired structure-function controlled nanomaterials.
      On the other hand, the reactor equipment for the synthesis of these tailored
      nanomaterials is of prime importance not only at laboratory-scale but also with
      view of up-scaling the synthetic processes into large-scale productions. Whilst
      the sequential three-stage scale-up from the conventional process (i.e., lab
      scale/pilot-scale/large-scale) using multi-purpose batch reactor is masked with
      complications, on the other hand, the interface of nanomaterials synthesis
      processes and continuous-flow microfluidic chemistry has demonstrated relatively
      superior process performance over conventional technologies. Consequently, the
      uses of continuous-flow microfluidics systems have recently attracted much
      research attention as versatile tools for the synthesis of various structured
      nanomaterials. In this review, we highlight and analyze the key achievements to
      date of adopting microfluidics technologies for the controlled synthesis of
      nanomaterials with well-defined structural properties desirable for the intended
      applications. We devote the significant emphasis on demonstrating the improved
      potential characteristics features of continuous-flow microfluidics as a capable
      technology to provide efficient synthesis processes for the production of various
      nanosized scale structured materials with precise control of the involved
      chemistry. Moreover, we discuss the novel process window opportunities of
      hyphenated microfluidics nanoparticles synthesis with the in-situ or in-line
      structure characterization during synthesis under real-time reaction conditions
      which provide interesting insights and experimental evidence on nanoparticle
      growth mechanisms.

PMID- 24749430
TI  - Ultrafast laser ablation in liquids for nanomaterials and applications.
AB  - We present an inclusive overview of the ultrafast ablation technique performed in
      liquids. Being a comparatively new method, we bring out the recent progress
      achieved, present the challenges ahead, and outline the future prospects for this
      technique. The review is conveniently divided into five parts: (a) a succinct
      preamble to the technique of ultrafast ablation in liquids (ULAL) is provided. A
      brief introduction to the conventional ns ablation is also presented for the sake
      of completeness (b) fundamental physical processes involved in this technique are
      elaborated (c) specific advantages of the technique compared to other physical
      and chemical methodologies are enumerated (d) applications of this technique in
      photonics; biomedical and explosives detection [using surface-enhanced Raman
      scattering (SERS)] is updated (e) future prospects describing the potential of
      this technique for creating unique nanoparticles (NPs) and nanostructures (NSs)
      for niche applications. We also discuss some of the recently reported significant
      results achieved in a variety of materials, especially metals, using this
      technique. Furthermore, we present some of our own experimental data obtained
      from ULAL of Ag, Cu, and Zn in a variety of liquids such as acetone, water,
      acetonitrile etc. The generated NPs (colloidal solutions) and NSs (on substrates)
      have been successfully utilized for nonlinear optical, SERS, and biomedical
      applications.

PMID- 24749431
TI  - Recent developments in electrospinning of nanofiber yarns.
AB  - Nanofibers possess high surface area and excellent porosity. Though nanofibers
      can be produced by a variety of techniques, electrospinning stands distinct
      because of its simplicity and flexibility in processing different polymer
      materials, and ability to control fiber diameter, morphology, orientation, and
      chemical component. Nonetheless, electrospun nanofibers are predominantly
      produced in the form of randomly oriented fiber webs, which restrict their wide
      use. Converting nanofibers into twisted continuous bundles, i.e., nanofiber
      yarns, can improve their strength and facilitate their subsequent processes, but
      remains challenging to make. Nanofiber yarns also create enormous opportunities
      to develop well-defined three-dimensional nanofibrous architectures. This review
      article gives an overview of the state-of-the-art techniques for electrospinning
      of nanofiber yarns and control of nanofiber alignment. A detailed account on
      techniques to produce twisted/non-twisted short bundles and continuous yarns are
      discussed.

PMID- 24749432
TI  - Cadmium-based quantum dots: preparation, surface modification, and applications.
AB  - Cadmium-based quantum dots (QDs) have the advantage of broad UV excitation,
      narrow emission, bright photoluminescence (PL), and high photostability, which
      make them fine applications in bio-imaging, electroluminescence (EL) and
      photovoltaic (PV) devices, catalytic hydrogen production, sensors, etc. This
      review article summarizes the synthetic methods such as organometallic and
      aqueous approaches, and the techniques employed to prepare high-quality QDs
      including microwave, hydrothermal, and ultrasound. QDs and their applications are
      emphasized for their unique properties, especially in the preparation of near
      infrared (NIR). Moreover, the synthesis of novel cadmium-based QDs with metal
      chalcogenide complexes (MCCs) as ligands has been introduced, which can overcome
      traditional QDs' disadvantages of poor interparticle coupling and conducting.
      Following the synthetic methods, the latest development of surface modification
      is summarized, which is important and necessary for the applications of QDs.

PMID- 24749433
TI  - Non-covalently functionalized carbon nanostructures for synthesizing carbon-based
      hybrid nanomaterials.
AB  - Carbon nanostructures (CNSs) such as carbon nanotubes, graphene sheets, and
      nanodiamonds provide an important type of substrate for constructing a variety of
      hybrid nanomaterials. However, their intrinsic chemistry-inert surfaces make it
      indispensable to pre-functionalize them prior to immobilizing additional
      components onto their surfaces. Currently developed strategies for
      functionalizing CNSs include covalent and non-covalent approaches. Conventional
      covalent treatments often damage the structure integrity of carbon surfaces and
      adversely affect their physical properties. In contrast, the non-covalent
      approach offers a non-destructive way to modify CNSs with desired functional
      surfaces, while reserving their intrinsic properties. Thus far, a number of
      surface modifiers including aromatic compounds, small-molecular surfactants,
      amphiphilic polymers, and biomacromolecules have been developed to non-covalently
      functionalize CNS surfaces. Mediated by these surface modifiers, various
      functional components such as organic species and inorganic nanoparticles were
      further decorated onto their surfaces, resulting in versatile carbon-based hybrid
      nanomaterials with broad applications in chemical engineering and biomedical
      areas. In this review, the recent advances in the generation of such hybrid
      nanostructures based on non-covalently functionalized CNSs will be reviewed.

PMID- 24749434
TI  - Recent advances in superhydrophobic nanomaterials and nanoscale systems.
AB  - This review describes the recent advances in the field of superhydrophobic
      nanomaterials and nanoscale systems. The term superhydrophobic is defined from
      the surface properties when the surface shows the contact angle (CA) higher than
      150 degrees. This could be well known from the lotus effect due to the non-stick
      and self-cleaning properties of the lotus leaf (LL). We briefly introduced the
      methods of preparing superhydrophobic surfaces using top-down approaches, bottom
      up approaches and a combination of top-down and bottom-up approaches and various
      ways to prepare superhydrophobic nanomaterials and nanoscale systems using the
      bio-inspired materials, polymer nanocomposites, metal nanoparticles graphene
      oxide (GO) and carbon nanotubes (CNTs). We also pointed out the recent
      applications of the superhydrophobic nanomaterials and nanoscale systems in oil
      spill capture and separations, self-cleaning and self-healing systems, bio
      medicals, anti-icing and anti-corrosive, electronics, catalysis, textile fabrics
      and papers etc. The review also highlights the visionary outlook for the future
      development and use of the superhydrophobic nanomaterials and nanoscale systems
      for a wide variety of applications.

PMID- 24749435
TI  - Electrical characterization of organic monolayers at a nanoscale.
AB  - This study investigates the electrical properties of viologen derivatives at a
      nanoscale and analyzes it using a scanning tunneling microscopy (STM) in order to
      apply viologen molecules that represent a function in electron transfer mediators
      as a molecular electronic device. In addition, we measure conformational changes
      in the viologen molecular protrusions using STM and investigate changes in the
      width and height of the alkyl group that are due to the change in the polarity of
      viologen molecules by electron charges. In this experiment, high peak current is
      observed, such as a rectification at +1.14 V. Thus, according to the results of
      this experiment the rectification ratio [RR = J (at +2.5 V)/J (at -2.5 V)] of the
      viologen is found by 4.47 (HSC8VC8SH). Similar results are also obtained in some
      other cases of viologen derivatives.

PMID- 24749436
TI  - Organic field-effect transistors by a solvent vapor annealing process.
AB  - Organic field-effect transistor (OFET) attracts great interests from scientific
      research and industrial application because of its low-cost fabrication and
      excellent mechanical flexibility. Yet the charge carrier mobility of typical OFET
      is still around 1-5 cm2/Vs and needs to be further enhanced, ideally by cost
      effective processes or treatments. Here we review one of the straightforward but
      effective methods, solvent vapor annealing (SVA), to improve the crystallinity of
      organic semiconductor film leading enhancement of charge carrier mobility in
      OFETs. We start by introducing the basic mechanism of SVA, followed by
      experimental works on small molecules and then conjugated polymers. Along with
      those examples, we discuss the important factors in using SVA to form highly
      crystalline conjugated molecule films or organic single crystals to achieve high
      performance OFETs.

PMID- 24749437
TI  - Resistive switching effect in titanium oxides.
AB  - Resistive switching (RS) phenomena have been vigorously investigated in a large
      variety of materials and highlighted for its preeminent potential for the future
      nonvolatile semiconductor memory applications or reconfigurable logic circuits.
      Among the various resistive switching materials, the binary metal oxides
      demonstrate more advantageous for micro- or nano-electronics applications due to
      their simpler fabrication process and compatibility with conventional CMOS
      technology, though the mechanisms are controversial due to the diversity of RS
      effects. This review mainly focuses on the current understanding of the
      microscopic nature of RS in titanium oxides, in which the working mechanisms can
      be categorized into thermochemical metallization mechanism, valence change
      mechanism, and electrostatic/electronic mechanism. The approaches developed to
      investigate the RS and the specific switching processes related to different
      mechanisms are addressed. Since titanium oxides are oxygen-vacancy doped
      semiconductors, the role of defects is analyzed in detail and possible effective
      strategies to improve the performance of RS are addressed.

PMID- 24749438
TI  - The impact of tunnel oxide nitridation to reliability performance of charge
      storage non-volatile memory devices.
AB  - This paper is written to review the development of critical research on the
      overall impact of tunnel oxide nitridation (TON) with the aim to mitigate
      reliability issues due to incessant technology scaling of charge storage NVM
      devices. For more than 30 years, charge storage non-volatile memory (NVM) has
      been critical in the evolution of intelligent electronic devices and continuous
      development of integrated technologies. Technology scaling is the primary
      strategy implemented throughout the semiconductor industry to increase NVM
      density and drive down average cost per bit. In this paper, critical reliability
      challenges and key innovative technical mitigation methods are reviewed. TON is
      one of the major candidates to replace conventional oxide layer for its superior
      quality and reliability performance. Major advantages and caveats of key TON
      process techniques are discussed. The impact of TON on quality and reliability
      performance of charge storage NVM devices is carefully reviewed with emphasis on
      major advantages and drawbacks of top and bottom nitridation. Physical mechanisms
      attributed to charge retention and V(t) instability phenomenon are also reviewed
      in this paper.

PMID- 24749439
TI  - Nanopatterning by laser interference lithography: applications to optical
      devices.
AB  - A systematic review, covering fabrication of nanoscale patterns by laser
      interference lithography (LIL) and their applications for optical devices is
      provided. LIL is a patterning method. It is a simple, quick process over a large
      area without using a mask. LIL is a powerful technique for the definition of
      large-area, nanometer-scale, periodically patterned structures. Patterns are
      recorded in a light-sensitive medium that responds nonlinearly to the intensity
      distribution associated with the interference of two or more coherent beams of
      light. The photoresist patterns produced with LIL are the platform for further
      fabrication of nanostructures and growth of functional materials used as the
      building blocks for devices. Demonstration of optical and photonic devices by LIL
      is reviewed such as directed nanophotonics and surface plasmon resonance (SPR) or
      large area membrane reflectors and anti-reflectors. Perspective on future
      directions for LIL and emerging applications in other fields are presented.

PMID- 24749440
TI  - Structure and stability of nanoscale bimetallic clusters.
AB  - This paper reviews the recent research and development of bimetallic clusters.
      Small bimetallic nanoscale clusters often have physical and chemical properties
      that are distinct from those of their pure bulk counterparts and suggestive of
      novel applications. Their chemical and physical properties can be controlled by
      varying the cluster size and composition as well as the temperature. Therefore
      the starting point for an understanding of bimetallic clusters is the study of
      their structures. The typical most stable structure: cuboctahedron, decahedron,
      icosahedron and Marks decahedron etc. According to the elemental distribution in
      bimetallic clusters, they can be divided into solid solution type, core/shell,
      eutectic-like etc. Complete phase separation is found in some bimetallic systems
      in specific conditions. The most stable structure of a bimetallic cluster is
      affected by the interatomic interaction potential, especially the alloying
      interaction, radius of the metal atom or the nearest neighbor distance in its
      stable bulk crystalline, temperature, concentration of each component, and the
      size of the clusters. In certain dynamic synthesis conditions such as substrate,
      non-most stable structure can form and exist, and can transform into a stable
      structure under some conditions such as heating.

PMID- 24749441
TI  - Electronic and structural response of nanomaterials to ultrafast and ultraintense
      laser pulses.
AB  - The interaction of materials with ultrafast and ultraintense laser pulses is a
      current frontier of science both experimentally and theoretically. In this
      review, we briefly discuss some recent theoretical studies by the present authors
      with our method of semiclassical electron-radiation-ion dynamics (SERID). In
      particular, Zhou et al. and Jiang et al. respectively, determined the optimal
      duration and optimal timing for a series of femtosecond scale laser pulses to
      excite a specific vibrational mode in a general chemical system. A set of such
      modes can be used as a "fingerprint" for characterizing a particular molecule or
      a complex in a solid. One can therefore envision many applications, ranging from
      fundamental studies to detection of chemical or biological agents. Allen et al.
      proved that dimers are preferentially emitted during photofragmentation of C60
      under an ultrafast and ultraintense laser pulse. For interactions between laser
      pulses and semiconductors, e.g., GaAs, Si and InSb, besides experimentally
      accessible optical properties--epsilon(omega) and chi(2)-Allen et al. offered
      many other indicators to confirm the nonthermal nature of structural changes
      driven by electronic excitations and occurring during the first few hundred
      femtoseconds. Lin et al. found that, after the application of a femtosecond laser
      pulse, excited electrons in materials automatically equilibrate to a Fermi-Dirac
      distribution within roughly 100 fs, solely because of their coupling to the
      nuclear motion, even though the resulting electronic temperature is one to two
      orders of magnitude higher than the kinetic temperature defined by the nuclear
      motion.

PMID- 24749442
TI  - Silver-gold bimetallic nanoparticles and their applications as optical materials.
AB  - Recently, nanoscale metallic particles have been studied extensively due to their
      tunable and strong optical properties that are well beyond those of organic
      chromophores. As monometallic nanoparticles have shown strong but narrow
      absorption bands within the ultraviolet and visible wavelengths, the preparation
      of bimetallic core-shell structures can give rise to strong, wide, and tunable
      absorption bands across the visible to near infrared areas. The silver-gold
      bimetallic nanoparticles with core-shell structures can offer unique physical and
      optical properties inaccessible to monometallic systems. These nanoparticles have
      been utilized in many areas of research including chemical catalysis, surface
      enhanced Raman spectroscopy, and photothermal therapy. This review article is a
      comprehensive overview of bimetallic nanoparticle systems consisting of gold and
      silver; it is based on the recent advances in wet-chemical synthetic
      methodologies, the characterization of size and shape-dependent optical
      properties, and various optically driven applications including catalysis, signal
      enhancing devices, and biomedical purposes.

PMID- 24749443
TI  - Advances in rare earth spectroscopy and applications.
AB  - Rare earth (RE) elements are prime constituents in a large amount of innovative
      materials and several technological advances would not be possible without their
      contribution. In this review, recent progress in the field of rare earth
      spectroscopy is highlighted, with a special emphasis on clean energy, sensors and
      telecommunications, providing a broad view on past and recent developments.

PMID- 24749444
TI  - Photocatalytical nanocomposites: a review.
AB  - This review focuses on photocatalytically active nanocomposites that are based on
      the photoactive nanoparticles, or nanostructured particles captured on the
      surface of the different powderized carriers. Nanosized and nanostructured oxides
      and sulfides with selected metal cations (Ti, Zn, Cd, Fe, etc.) are intensively
      studied as the photocatalysts for different purposes. The nanodimension of these
      particles brings several disadvantages, among them being the negative impact on
      human health, which is a widely discussed topic nowadays. The nanoparticles can
      permeate through living tissue and enter living cells and thus a strong effort
      focused on diminishing this problem is the subject of research activities by many
      groups. One possible way to achieve control of the nanoparticles' mobility is
      capturing them on the surface of suitable particulate carriers with dimensions on
      the order of tenths and hundredths of microns whereas this approach leads to
      formation of new composite material. Clay minerals, silicates, carbonaceous
      materials, and other particulate matter are intensively studied for these
      purposes and proper selection of the substrate can bring additional functionality
      to the final composite. Very often the photoactivity, antibacterial properties,
      electrical conductivity, and other properties are significantly enhanced in the
      case of this kind of composite materials. Strong adhesion between the
      nanoparticles and the surface of the selected substrate is essential for the
      stability of the final composites. Characterization of the adhesion energies
      using laboratory experiments is quite difficult and molecular modeling can bring
      valuable information about the character of interactions at the interface of
      nanoparticles and substrate.

PMID- 24749445
TI  - Preparation of electrophoretic nanoparticles for electronic paper.
AB  - As an electronic alternative for printed media, the E-paper has ultralow power
      consumption, reduced eyestrain, high contrast ratio. Electrophoretic displays are
      one of the most promising E-paper technologies, which are now widely used in
      consumer products. The properties of the electrophoretic display are mainly
      determined by the composition, size, light scattering properties, and density of
      the electrophoretic nanoparticles. First, we introduce the preparation of white
      and black electrophoretic nanoparticles, because the monochrome E-paper has
      achieved commercial success. Then the structure and properties of color
      electrophoretic nanoparticles for color E-paper products are discussed. In
      addition, the enhanced and novel electrophoretic nanoparticles are now propelling
      the development of next-generation E-paper with new applications. Finally, the
      active area of the preparation of electrophoretic nanoparticles is highlighted in
      terms of the development of future E-paper.

PMID- 24749446
TI  - Hyperbranched polymers and dendrimers as templates for organic/inorganic hybrid
      nanomaterials.
AB  - This paper reviews the recent research and development of hyperbranched polymers
      (HPs) and dendrimers, and their use as templates for organic-inorganic hybrid
      nanomaterials. Hyperbranched polymers (HPs) are highly branched macromolecules
      with three-dimensional globular structures featuring unique properties such as
      low viscosity, high solubility, and a large number of terminal functional groups
      compared to their linear analogs. They are easily prepared by (1) condensation
      polymerization, (2) self-condensing vinyl copolymerization (SCVCP), and (3) ring
      opening multibranch polymerization methods. Organic-inorganic hybrid
      nanomaterials are synthesized by a template approach using HPs/dendrimers.
      Monometallic, bimetallic (alloy and core/shell), semiconductor, and metal oxide
      nanoparticles have been prepared by this route. The dendrimer component of these
      composites serves not only as a template for preparing the nanoparticles but also
      as a stabilizer for the nanoparticles.

PMID- 24749447
TI  - Synthesis of carbon nanowall by plasma-enhanced chemical vapor deposition method.
AB  - Plasma-enhanced chemical vapor deposition (PECVD) is widely used for the
      synthesis of carbon materials, such as diamond-like carbons (DLCs), carbon
      nanotubes (CNTs) and carbon nanowalls (CNWs). Advantages of PECVD are low
      synthesis temperature compared with thermal CVD and the ability to grow
      vertically, free-standing structures. Due to its self-supported property and high
      specific surface area, CNWs are a promising material for field emission devices
      and other chemical applications. This article reviews the recent process on the
      synthesis of CNW by the PECVD method. We briefly introduce the structure and
      properties of CNW with characterization techniques. Growth mechanism is also
      discussed to analyze the influence of plasma conditions, substrates, temperature,
      and other parameters to the final film, which will give a suggestion on parameter
      modulation for desired film.

PMID- 24749448
TI  - Selenium nanomaterials: applications in electronics, catalysis and sensors.
AB  - This review provides insights into the synthesis, functionalization, and
      applications of selenium nanoparticles in electronics, optics, catalysis and
      sensors. The variation of physicochemical properties such as particle size,
      surface area, and shape of the selenium nanoparticles and the effect of
      experimental conditions has also been discussed. An overview has also been
      provided on the fundamental electrical and optical properties of selenium
      nanomaterials as well as their utilization in different research fields. The work
      presents an insight on selenium nanoparticles with interesting properties and
      their future applications.

PMID- 24749449
TI  - Rare earth fluoride nano-/microstructures: hydrothermal synthesis, luminescent
      properties and applications.
AB  - Rare earth fluoride materials have attracted wide interest and come to the
      forefront in nanophotonics due to their distinct electrical, optical and magnetic
      properties as well as their potential applications in diverse fields such as
      optical telecommunication, lasers, biochemical probes, infrared quantum counters,
      and medical diagnostics. This review presents a comprehensive overview of the
      flourishing field of rare earth fluorides materials in the past decade. We
      summarize the recent research progress on the preparation, morphology,
      luminescent properties and application of rare earth fluoride-based luminescent
      materials by hydrothermal systems. Various rare earth fluoride materials are
      obtained by fine-tuning of experimental conditions, such as capping agents,
      fluoride source, acidity, temperature and reaction time. The controlled
      morphology, luminescent properties and application of the rare earth fluorides
      are briefly discussed with typical examples.

PMID- 24749450
TI  - Characterization strategies for Mn2O3 nanomaterials.
AB  - Transition metal oxides belong to a class of versatile materials that are vitally
      important for developing new materials with functionality and smartness. Research
      on manganese oxides has been a key topic among studies on transition metal
      oxides. This is due to their potential applications in diverse areas, including
      rechargeable lithium ion batteries, catalysis, molecular adsorption, gas sensors,
      energy storage, and magnetics. In this review, we will elucidate in detail
      various characterization strategies, including temperature-dependent growth,
      micro/nanostructures, Raman, X-ray photoelectron spectroscopy, Fourier transform
      infrared spectroscopy, and electron spin resonance, for Mn2O3 nanocrystals,
      highlighting contributions from our laboratory. This review article mainly
      focuses on the wide-ranging research effort on the development of preparation
      methodologies and the assessment of various characterization strategies in Mn2O3
      nanomaterials. The main purpose is to provide the readers a comprehensive
      understanding of the research progress of manganese oxides. This is an
      interdisciplinary work that integrates the areas of physics, chemistry, materials
      science, and nanotechnology.

PMID- 24749451
TI  - Beyond carbon nanotubes: adsorptions on and electronic structures of silicon
      nanotubes.
AB  - In this paper, we have reviewed some of the recent theoretical studies on the
      electronic and structural properties of silicon nanotubes from single-walled to
      double-walled nanostructures, primarily focusing on the studies performed by the
      present authors. The studies so far have not indicated any metallic behavior in
      both single-walled and double-walled silicon nanotubes. Atomic and molecular
      adsorptions of elements including hydrogen, oxygen and alkali metals on single
      walled silicon nanotubes are also reviewed and new results presented in detail. A
      systematic study of molecular adsorption and co-adsorptions of hydrogen and
      oxygen molecules in zigzag silicon nanotube (SiNT) has been performed using
      hybrid density functional theory. For adsorption of two hydrogen molecules in
      SiNT (10, 0), the original diatomic molecular structure was maintained after
      adsorption. The most preferred final site for hydrogen molecules is the on-top
      site. For adsorption of two oxygen molecules, the most preferred sites are bridge
      sites, which are the parallel or zigzag bridge sites. Complete dissociation,
      partial dissociation and non-dissociation were observed for adsorption of two
      oxygen molecules. Peroxide structure and Si-O-O structures have also been
      observed in adsorption of two oxygen molecules with smaller adsorption energies
      rather than complete dissociation. For the co-adsorption of one hydrogen molecule
      and one oxygen molecule, the hydrogen molecule is slightly polarized, and a
      suppression effect on HOMO-LUMO gap was observed.

PMID- 24749452
TI  - Visualization of atom's orbits.
AB  - High-resolution imaging techniques have been used to obtain views of internal
      shapes of single atoms or columns of atoms. This review article focuses on the
      visualization of internal atomic structures such as the configurations of
      electron orbits confined to atoms. This is accomplished by applying visualization
      techniques to the reported images of atoms or molecules as well as static and
      dynamic ions in a plasma. It was found that the photon and electron energies
      provide macroscopic and microscopic views of the orbit structures of atoms,
      respectively. The laser-imaged atoms showed a rugged orbit structure, containing
      alternating dark and bright orbits believed to be the pathways for an externally
      supplied laser energy and internally excited electron energy, respectively. By
      contrast, the atoms taken by the electron microscopy provided a structure of fine
      electron orbits, systematically formed in increasing order of grayscale
      representing the energy state of an orbit. This structure was identical to those
      of the plasma ions. The visualized electronic structures played a critical role
      in clarifying vague postulates made in the Bohr model. Main features proposed in
      the atomic model are the dynamic orbits absorbing an externally supplied
      electromagnetic energy, electron emission from them while accompanying light
      radiation, and frequency of electron waves not light. The light-accompanying
      electrons and ionic speckles induced by laser light signify that light is
      composed of electrons and ions.

PMID- 24749453
TI  - Swarm intelligence in bioinformatics: methods and implementations for discovering
      patterns of multiple sequences.
AB  - As a promising and innovative research field, bioinformatics has attracted
      increasing attention recently. Beneath the enormous number of open problems in
      this field, one fundamental issue is about the accurate and efficient
      computational methodology that can deal with tremendous amounts of data. In this
      paper, we survey some applications of swarm intelligence to discover patterns of
      multiple sequences. To provide a deep insight, ant colony optimization, particle
      swarm optimization, artificial bee colony and artificial fish swarm algorithm are
      selected, and their applications to multiple sequence alignment and motif
      detecting problem are discussed.

PMID- 24749454
TI  - Advances in rubber/halloysite nanotubes nanocomposites.
AB  - The research advances in rubber/halloysite nanotubes (rubber/HNTs) nanocomposites
      are reviewed. HNTs are environmentally-friendly natural nanomaterials, which
      could be used to prepare the rubber-based nanocomposites with high performance
      and low cost. Unmodified HNTs could be adopted to prepare the rubber/HNTs
      composites with improved mechanical properties, however, the rubber/HNTs
      nanocomposites with fine morphology and excellent properties were chiefly
      prepared with various modifiers by in situ mixing method. A series of rubber/HNTs
      nanocomposites containing several rubbers (SBR, NR, xSBR, NBR, PU) and different
      modifiers (ENR, RH, Si69, SA, MAA, ILs) have been investigated. The results
      showed that all the rubber/HNTs nanocomposites achieved strong interfacial
      interaction via interfacial covalent bonds, hydrogen bonds or multiple
      interactions, realized significantly improved dispersion of HNTs at nanoscale and
      exhibited excellent mechanical performances and other properties.

PMID- 24749455
TI  - Nanoscale control designs for systems.
AB  - Nanoscale control is the science of the control of objects at dimensions with 100
      nm or less and the manipulation of them at this level of precision. The desired
      attributes of systems under nanoscale control design are extreme high resolution,
      accuracy, stability, and fast response. An important perspective of investigation
      in nanoscale control design includes system modeling and precision control
      devices and materials at a nanoscale dimension, i.e., design of nanopositioners.
      Nanopositioners are mechatronic systems with an ultraprecise resolution down to a
      fraction of an atomic diameter and developed to move objects over a small range
      in nanoscale dimension. After reviewing a lot of existing literatures for
      nanoscale control designs, the way to successful nanoscale control is accurate
      position sensing and feedback control of the motion. An overview of nanoscale
      identification, linear, and nonlinear control technologies, and devices that are
      playing a key role in improving precision, accuracy, and response of operation of
      these systems are introduced in this research.

PMID- 24749456
TI  - Nano/microstructured ion exchange resins and their applications.
AB  - Ion exchange resins, due to their specific nano/microstructures and applications,
      have attracted great attention in the past decades. This paper reviews the recent
      advances and applications of nano/microstructured ion exchange resins, with an
      introduction to the preparation and property of different ion exchange resins.
      The applications of different ion exchange resins in catalysts, medicine,
      metallurgical regeneration, metals, and chemicals removal are summarized and
      discussed. The perspectives for the future developments of ion exchange resins
      are also proposed.

PMID- 24749457
TI  - Carbon nanofibers: synthesis and applications.
AB  - As a novel functional material, carbon nanofiber has many interesting
      applications in the chemical industry, material science, and energy storage
      fields. Chemical vapor dispersion and carbonization polymer nanofibers are the
      two important routes to synthesize carbon nanofibers. In this mini-review, the
      synthesis mechanisms of carbon nanofibers are illustrated and some novel
      applications of carbon nanofiber were also summarized.

PMID- 24749458
TI  - CO2 adsorption by functionalized nanoporous materials: a review.
AB  - This review highlights the recent advances in the development of functionalized
      nanoporous adsorbents for CO2 capture. Three main classes of materials are taken
      into account: zeolites, mesoporous silicates, and metal organic frameworks
      (MOFs). Proper modification of the cation content of zeolites, as well as the
      introduction of functional groups such as amine groups into ordered mesoporous
      silicates and MOFs, greatly enhance the CO2 adsorptive properties of these
      substrates. Specifically, cation-exchanged zeolites can be currently considered
      the benchmark for ordered nanoporous CO2 adsorbents, finding application also on
      a plant scale. Amino-functionalized mesoporous silicates tend to show a high
      affinity toward CO2: while this could be an advantage when pushed purification is
      needed, it also implies that full regeneration of the adsorbent can be achieved
      only by putting its surface in contact with a completely CO2-free environment. On
      the contrary, similarly modified MOFs show higher CO2 adsorption working
      capacities: this potentially makes them even better candidates than their
      mesoporous inorganic homologues for a plant scale use. However, the persisting
      lack of reliable methods for the pelletization of both ordered mesoporous
      silicates and MOFs creates a care for further development efforts in the next
      future.

PMID- 24749459
TI  - Mesoporous carbon nanomaterials as environmental adsorbents.
AB  - The transportation and diffusion of the guest objects or molecules in the porous
      carbon nanomaterials can be facilitated by reducing the pathway and resistance.
      The reduced pathway depends on the porous nature of carbon nanomaterials.
      Classification of porous carbon materials by the International Union of Pure and
      Applied Chemistry (IUPAC) has given a new opportunity to design the pores as per
      their applicability and to understand the mobility of ions, atoms, and molecules
      in the porous network of carbon materials and also advanced their countless
      applicability. However, synthesis of carbon nanomaterials with a desired porous
      network is still a great challenge. Although, remarkable developments have taken
      place in the recent years, control over the pores size and/or hierarchical porous
      architectures, especially in the synthesis of carbon nanospheres (CNSs) and
      ordered mesoporous carbon (OMCs) is still intriguing. The micro and mesoporous
      CNSs and OMCs have been prepared by a variety of procedures and over a wide range
      of compositions using various different surfactant templates and carbon
      precursors etc. The mechanisms of formation of micromesopore in the CNSs and OMCs
      are still evolving. On the other hand, the urge for adsorbents with very high
      adsorption capacities for removing contaminants from water is growing steadily.
      In this review, we address the state-of-the-art synthesis of micro and mesoporous
      CNSs and OMCs, giving examples of their applications for adsorptive removals of
      contaminants including our own research studies.

PMID- 24749460
TI  - Nanotechnology-based water treatment strategies.
AB  - The most important component for living beings on the earth is access to clean
      and safe drinking water. Globally, water scarcity is pervasive even in water-rich
      areas as immense pressure has been created by the burgeoning human population,
      industrialization, civilization, environmental changes and agricultural
      activities. The problem of access to safe water is inevitable and requires
      tremendous research to devise new, cheaper technologies for purification of
      water, while taking into account energy requirements and environmental impact.
      This review highlights nanotechnology-based water treatment technologies being
      developed and used to improve desalination of sea and brackish water, safe reuse
      of wastewater, disinfection and decontamination of water, i.e., biosorption and
      nanoadsorption for contaminant removal, nanophotocatalysis for chemical
      degradation of contaminants, nanosensors for contaminant detection, different
      membrane technologies including reverse osmosis, nanofiltration, ultrafiltration,
      electro-dialysis etc. This review also deals with the fate and transport of
      engineered nanomaterials in water and wastewater treatment systems along with the
      risks associated with nanomaterials.

PMID- 24749461
TI  - Water condensation: a multiscale phenomenon.
AB  - The condensation of water is a phenomenon occurring in multiple situations in
      everyday life, e.g., when fog is formed or when dew forms on the grass or on
      windows. This means that this phenomenon plays an important role within the
      different fields of science including meteorology, building physics, and
      chemistry. In this review we address condensation models and simulations with the
      main focus on heterogeneous condensation of water. The condensation process is,
      at first, described from a thermodynamic viewpoint where the nucleation step is
      described by the classical nucleation theory. Further, we address the
      shortcomings of the thermodynamic theory in describing the nucleation and
      emphasize the importance of nanoscale effects. This leads to the description of
      condensation from a molecular viewpoint. Also presented is how the nucleation can
      be simulated by use of molecular models, and how the condensation process is
      simulated on the macroscale using computational fluid dynamics. Finally, examples
      of hybrid models combining molecular and macroscale models for the simulation of
      condensation on a surface are presented.

PMID- 24749462
TI  - Suzuki coupling reaction using hybrid Pd nanoparticles.
AB  - This paper reviews recent developments in the field of hybrid Pd nanoparticles
      and their catalytic activity in the Suzuki coupling reaction, which is used
      extensively in the fabrication of both simple and complex biaryl compounds. We
      developed three types of Pd-silica hybrid nanoparticles. Pd/SiO2 nanobeads
      containing tiny Pd clusters, Pd@nickel phyllosilicate yolk-shell nanoparticles,
      Pd@porous SiO2 yolk-shell nanoparticles were synthesized, and they displayed
      highly efficient catalytic activity and excellent reusability. The hybrid
      nanoparticles also catalyzed the Suzuki coupling reaction with various
      substrates, including bromobenzene and chlorobenzene. This review also briefly
      discusses the synthesis procedure, structural characterization, and catalytic
      activity of hybrid Pd nanoparticles.

PMID- 24749463
TI  - Progress of quartz crystal microbalance in chiral analysis.
AB  - Chiral analysis is one of the most important/challenging analytical tasks due to
      the necessity for differentiation of very slight differences in the molecular
      configurations between chiral isomers. It consists of two processes, chiral
      recognition and signal transduction. Quartz crystal microbalance (QCM) holds a
      great promise for the next-generation sensors, due to its remarkable mass
      sensitivity, fast response, capable of online detection and low cost. It has been
      the focus of academic and practical research on chiral analysis during the last
      two decades. This review provides a detailed overview of recent advances made in
      chiral analysis based on QCM detection with regard to the recognition elements,
      which include synthetic macromolecules, molecular imprinting polymers (MIPs),
      proteins, amino acids and their derivatives, etc. The prospects of using QCM for
      chiral analysis are also put forward.

PMID- 24749464
TI  - Recent developments in heterogeneous catalyzed environmental remediation
      processes.
AB  - This article reports on recent developments in heterogeneous AOP processes such
      as photocatalysis, Fenton-like process and catalytic ozonation. The principle,
      mechanism, and influence of experimental conditions on the degradation of
      pollutants in heterogeneous catalytic ozonation and the photocatalytic process
      were discussed. Introducing solid catalysts substantially increased the
      efficiency of the ozonation process by producing hydroxyl radicals in the
      degradation process. The different types of catalyst, catalyst dosage, solution
      pH, ozone flow rate, water matrix and catalytic reusability and stability are
      reported on here. The list of various semiconductor materials used as
      photocatalysts, their light absorption properties, various light sources and
      surface properties such as surface area, pore size and pore volume as a factor in
      the photocatalytic degradation of various pollutants are discussed. The review
      article also discussed the pollutants degraded using these three processes.

PMID- 24749465
TI  - Pulse laser deposited nanostructured ZnO thin films: a review.
AB  - This review summarizes the work principles of pulse laser deposition (PLD)
      apparatus, physical processes like ablation, and plasma plume formation
      accompanying the deposition of un-doped ZnO from target to substrate material.
      Various modes of deposition and factors influencing the properties of thin films
      such as substrate temperature, background gas pressure, laser energy density
      (laser fluence), target to substrate distance, repetition rate, oxygen partial
      pressure in deposition chamber, deposition time and post growth annealing which
      control deposition parameters such as adsorption, desorption, surface diffusion,
      nucleation, and crystallization/re-crystallization are also discussed in this
      review. Moreover, various film properties such as morphology, roughness of the
      film surface, film thickness, grain size, optical transmittance, sensitivity,
      electrical conductivity, uniformity and electrical resistivity of the deposited
      ZnO thin films have also been enumerated in the present review.

PMID- 24749466
TI  - Nanostructured Mg-Al hydrotalcite as catalyst for fine chemical synthesis.
AB  - This paper reviews the recent research of nanostructured Mg-Al hydrotalcite (Mg
      Al HT) and its application as an efficient solid base catalyst for the synthesis
      of fine chemicals. Mg-Al HT has many beneficial features, such as low cost,
      selectivity, catalytic properties, and wide range of preparation and modification
      methods. They hold promise for providing sought-after, environmentally friendly
      technologies for the 21st century. Replacement of currently used homogeneous
      alkaline bases for the synthesis of fine chemicals by a solid catalyst can result
      in catalyst re-use and waste stream reduction. We introduce briefly the
      structure, properties and characterization of the nanostructured Mg-Al HT. The
      efficacy and benign applications of Mg-Al HT as an alternative solid base to
      homogenous catalysts in the synthesis of fine chemicals are then reviewed. The
      challenges for the future applications of Mg-Al HT in the synthesis of fine
      chemicals in terms of green protocol processes are discussed.

PMID- 24749467
TI  - GaN nanostructure-based light emitting diodes and semiconductor lasers.
AB  - GaN and related materials have received a lot of attention because of their
      applications in a number of semiconductor devices such as LEDs, laser diodes,
      field effect transistors, photodetectors etc. An introduction to optical
      phenomena in semiconductors, light emission in p-n junctions, evolution of LED
      technology, bandgaps of various semiconductors that are suitable for the
      development of LEDs are discussed first. The detailed discussion on
      photoluminescence of GaN nanostructures is made, since this is crucial to develop
      optical devices. Fabrication technology of many nanostructures of GaN such as
      nanowires, nanorods, nanodots, nanoparticles, nanofilms and their luminescence
      properties are given. Then the optical processes including ultrafast phenomena,
      radiative, non-radiative recombination, quantum efficiency, lifetimes of excitons
      in InGaN quantum well are described. The LED structures based on InGaN that give
      various important colors of red, blue, green, and their design considerations to
      optimize the output were highlighted. The recent efforts in GaN technology are
      updated. Finally the present challenges and future directions in this field are
      also pointed out.

PMID- 24749468
TI  - Preparation of nanoferrites and their applications.
AB  - Ferrites have a plethora of applications in the myriad fields of technology.
      Ferrites are widely used in conventional electronic, electrical, and magnetic
      devices. For the past two decades, since the discovery of the superparamagnetic
      nature of nanostructured ferrites, their applications in biotechnology and
      biomedical sciences as well as in advanced electronics and microwave devices have
      gained immense attention. In this review, the historical development of ferrite
      science and technology, and the synthesis methods for ferrite nanoparticle
      preparation and their applications have been discussed. Various synthetic methods
      with typical examples, their advantages as well as limitations have been
      discussed in details. Traditional industrial applications of various ferrites
      have also been discussed citing relevant patents. Recent developments on
      nanoferrite research in terms of synthetic methods as well as advanced
      applications have been discussed elaborately.

PMID- 24749469
TI  - Development and applications of 3-dimensional integration nanotechnologies.
AB  - Unlike conventional two-dimensional (2D) planar structures, signal or power is
      supplied through through-silicon via (TSV) in three-dimensional (3D) integration
      technology to replace wires for binding the chip/wafer. TSVs have becomes an
      essential technology, as they satisfy Moore's law. This 3D integration technology
      enables system and sensor functions at a nanoscale via the implementation of a
      highly integrated nano-semiconductor as well as the fabrication of a single chip
      with multiple functions. Thus, this technology is considered to be a new area of
      development for the systemization of the nano-bio area. In this review paper, the
      basic technology required for such 3D integration is described and methods to
      measure the bonding strength in order to measure the void occurring during
      bonding are introduced. Currently, CMOS image sensors and memory chips associated
      with nanotechnology are being realized on the basis of 3D integration technology.
      In this paper, we intend to describe the applications of high-performance nano
      biosensor technology currently under development and the direction of development
      of a high performance lab-on-a-chip (LOC).

PMID- 24749470
TI  - Review on palladium-containing perovskites: synthesis, physico-chemical
      properties and applications in catalysis.
AB  - This review reports on the recent advances in the synthesis and physico-chemical
      properties of palladium-containing perovskites. Initially, the perovskite
      structure is briefly reviewed, then palladium-containing perovskites synthesis
      and physico-chemical properties are detailed. The applications of palladium
      containing perovskites in catalysis; namely, NO reduction, methane combustion,
      methanol as well as ethanol oxidation, are briefly highlighted. The involvement
      and the important contribution of palladium-containing perovskites in cross
      coupling reactions, especially Suzuki-Miyaura, Sonogashira, Ulmann and Grignard,
      are discussed.

PMID- 24749471
TI  - Biogenic synthesis of gold and silver nanoparticles by seed plants.
AB  - Nanoparticles have an enormous range of biomedical and environmental applications
      and can be used for development of various nanodevices for diagnostics and drug
      delivery. Biogenic production of nanoparticles, that is of silver and gold, by
      seed plants, especially flowering plants, has evoked considerable interest in the
      last decade. Different organs of plants as well as callus cultures have been used
      for the production of these metal nanoparticles. It is possible to regulate the
      geometry of the nanoparticles by modifying the experimental parameters. In many
      cases the phytosynthesized gold and silver nanoparticles have been demonstrated
      to be potentially useful for treatment of various diseases. The production of
      gold and silver nanoparticles by diverse species of seed plants and their
      biological activity are discussed in this article.

PMID- 24749472
TI  - Biosynthesis of silver nanoparticles.
AB  - Metal nanoparticles have unique optical, electronic, and catalytic properties.
      There exist well-defined physical and chemical processes for their preparation.
      Those processes often yield small quantities of nanoparticles having undesired
      morphology, and involve high temperatures for the reaction and the use of
      hazardous chemicals. Relatively, the older technique of bioremediation of metals
      uses either microorganisms or their components for the production of
      nanoparticles. The nanoparticles obtained from bacteria, fungi, algae, plants and
      their components, etc. appear environment-friendly, as toxic chemicals are not
      used in the processes. In addition to this, the formation of nanoparticles takes
      place at almost normal temperature and pressure. Control of the shape and size of
      the nanoparticles is possible by appropriate selection of the pH and temperature.
      Three important steps are the bioconversion of Ag+ ions, conversion of desired
      crystals to nanoparticles, and nanoparticle stability. Generally, nanoparticles
      are characterized by the UV-visible spectroscopy and use of the electron
      microscope. Silver nanoparticles are used as antimicrobial agents and they
      possess antifungal, anti-inflammatory, and anti-angiogenic properties. This
      review highlights the biosynthesis of silver nanoparticles by various organisms,
      possible mechanisms of their synthesis, their characterization, and applications
      of silver nanoparticles.

PMID- 24749473
TI  - Conformal growth of anodic nanotubes for dye-sensitized solar cells: part II.
      Nonplanar electrode.
AB  - Anodic titania nanotube array features highly ordered alignment as well as porous
      nature, and exhibits intriguing properties when employed in a variety of
      applications. All these profit from the continuous efforts on controlling the
      nanotube configurations. Recently, nonplanar electrodes have also been used to
      grow the nanotubes besides the conventional planar counterparts. As such, it is
      of great interest and significance to complete a picture to link the nanotubes
      grown on planar and various nonplanar electrodes for a comprehensive
      understanding of nanotube growing manners, in an attempt to boost their future
      applications. In the first part of this review, planar electrodes are focused
      with regard to nanotube growth and application in dye-sensitized solar cells. In
      this part, the nanotubes grown on patterned or curved surfaces are discussed
      first with reference to a similar structure of alumina nanopores, which are
      subsequently used to mirror the growth of nanotubes on cylindrical electrodes
      (i.e., titanium wires or meshes). The last section focuses on titanium tubular
      electrodes which are attractive for thermal fluids in view of the drastically
      reduced thermal conductivity in the presence of anodic nanotubes. As a recent hot
      topic, wire-shaped dye-sensitized solar cells are deliberated in terms of cell
      structure, efficiency calculation, merits, challenges and outlook.

PMID- 24749474
TI  - Micro- and nano-structured metal oxides based chemical sensors: an overview.
AB  - This article examines various kinds of chemical sensors, their mechanism of
      operation and the ways to improve their performance. It reports the results of
      exploratory investigation of binary composite polycrystalline thick-films such as
      SnO2-WO3, SnO2-In2O3, and SnO2-ZnO for the detection of volatile organic compound
      (isopropanol) are reported. It also contains an overview on the status of the new
      types of metal oxide based nanostructured sensors, such as nano belts, nanorods,
      nanotubes, nanofibers, nanocomposites, etc.

PMID- 24749475
TI  - Ferroelectric polymer nanostructures: fabrication, structural characteristics and
      performance under confinement.
AB  - Ferroelectric polymers have recently attracted tremendous research interest due
      to their potential application in various emerging flexible devices.
      Nanostructured ferroelectric polymer materials, such as nanorods, nanotube, and
      nanowires, are essential for miniaturization of the relevant electronic
      components. More importantly, their improved sensitivity and functionality may be
      used to enhance the performance of existing devices or to develop and design new
      devices. In this article, the recently developed methods for fabricating
      ferroelectric polymer nanostructures are briefly reviewed. In particular, the
      distinct crystallization behaviors confined at the nanometer scale, the
      nanoconfinement induced structural change, their influence on the physical
      properties of the ferroelectric polymer nanostructures, and the possible
      underlying mechanisms are discussed.

PMID- 24749476
TI  - Hydrazone-bearing PMMA-functionalized magnetic nanocubes as pH-responsive drug
      carriers for remotely targeted cancer therapy in vitro and in vivo.
AB  - To develop vehicles for efficient chemotherapeutic cancer therapy, we report a
      remotely triggered drug delivery system based on magnetic nanocubes. The
      synthesized magnetic nanocubes with average edge length of around 30 nm acted as
      cores, whereas poly(methyl methacrylate) (PMMA) was employed as an intermediate
      coating layer. Hydrazide was then tailored onto PMMA both for doxorubicin (DOX)
      loading and pH responsive drug delivery via the breakage of hydrazine bonds. The
      successful fabrication of the pH responsive drug carrier was confirmed by
      transmission electron microscopy, Fourier transform infrared spectroscopy,
      thermogravimetric analysis, and magnetic hysteresis loops, respectively. The
      carrier was stable at neutral environment and doxorubicin released at pH of 5.0.
      Cell viability assay and confocal laser scanning microscopy observations
      demonstrated that the loaded DOX could be efficiently released after cellular
      endocytosis and induced cancer cells apoptosis thereby. More importantly, the
      carrier could be guided to the tumor tissue site with an external magnetic field
      and led to efficient tumor inhibition with low side effects, which were reflected
      by magnetic resonance imaging (MRI), change of tumor size, TUNEL staining, and
      H&E staining assays, respectively. All results suggest that hydrazide-tailoring
      PMMA-coated magnetic nanocube would be a promising pH-responsive drug carrier for
      remotely targeted cancer therapy in vitro and in vivo. 

PMID- 24749477
TI  - Total synthesis of (-)-lepenine.
AB  - The first asymmetric total synthesis of lepenine has been accomplished. The
      synthesis features a tethered intramolecular Diels-Alder reaction, an
      intramolecular Mannich reaction, and a Diels-Alder reaction between an ortho
      quinone monoketal and ethylene, resulting in stereoselective construction of the
      unique hexacyclic system. 

PMID- 24749478
TI  - Formation of layered Fe(II)-hydroxides during Fe(II) sorption onto clay and metal
      oxide substrates.
AB  - Sorption of Fe(II) in anoxic aqueous suspensions of gamma-Al2O3, smectitic clay
      and amorphous silica was studied as a function of pH (5.0-10.0) and reaction time
      (up to 110 days), using batch experiments complemented with synchrotron X-ray
      absorption spectroscopic analyses. Formation of secondary Fe(II) precipitates was
      observed at pH > 7 in all systems, with the rate of precipitation and the types
      of precipitates formed varying with pH and substrate type. Sorption of Fe(II) on
      gamma-Al2O3 at pH >= 7.0 and onto clay at pH 7.0 and 7.5 led to formation of
      Fe(II)-Al(III) layered double hydroxides, whereas poorly crystalline
      trioctahedral Fe(II)-phyllosilicates formed in the amorphous SiO2 suspensions at
      pH > 7.5 and in the clay suspensions at pH 8.0. The rate and extent of Fe(II)
      sorption increased with pH, underscoring the importance of pH in regulating
      precipitate formation. Notably slower Fe(II) precipitation in the clay
      suspensions compared to gamma-Al2O3 and SiO2 is attributed to relatively low
      availability of substrate-derived Al and Si. Our findings demonstrate that
      sorbent type, pH and reaction time are important factors affecting precipitation
      of secondary Fe(II) minerals in anoxic environments, and suggest substantial
      complexity in the type and reactivity of Fe(II) sorption products that may form. 

PMID- 24749479
TI  - Impact of pretransplant anti-HLA antibodies on outcomes in lung transplant
      candidates.
AB  - RATIONALE: The prevalence of anti-HLA antibodies in lung transplant candidates
      and their impact on waitlist and transplant outcomes is not known. OBJECTIVES: We
      examined the prevalence of pretransplant anti-HLA antibodies at varying
      thresholds and evaluated their impact on outcomes before and after lung
      transplantation. METHODS: We performed a single-center retrospective cohort study
      including all patients listed for lung transplantation between January 2008 and
      August 2012. Per protocol, transplant candidates were assessed by solid phase
      LABscreen mixed Class I and II and LABscreen Single Antigen assays. MEASUREMENTS
      AND MAIN RESULTS: Among 224 patients, 34% had anti-HLA antibodies at mean
      fluorescent intensity (MFI) greater than or equal to 3,000 (group III), and 24%
      had antibodies at MFI 1,000 to 3,000 (group II). Ninety percent of the patients
      with pretransplant anti-HLA antibodies had class I antibodies, whereas only seven
      patients developed class II alone. Patients in group III were less likely to
      receive transplants than patients without any anti-HLA antibodies (group I) (45.5
      vs. 67.7%, P = 0.005). Wait time to transplant was longer in group III than group
      I, although this difference did not meet statistical significance, and waitlist
      mortality was similar. Among transplant recipients, antibody-mediated rejection
      (AMR) was more frequent in group III than in group II (20% vs. 0%, P = 0.01) or
      group I (6.3%, P = 0.05). CONCLUSIONS: The presence of anti-HLA antibodies at the
      high MFI threshold (>3,000) was associated with lower transplant rate and higher
      rates of AMR. Screening for anti-HLA antibodies using the 3,000 MFI threshold may
      be important in managing transplant candidates and recipients.

PMID- 24749480
TI  - Estrogenic endocrine-disrupting chemicals: molecular mechanisms of actions on
      putative human diseases.
AB  - Endocrine-disrupting chemicals (EDC), including phthalates, bisphenol A (BPA),
      phytoestrogens such as genistein and daidzein, dichlorodiphenyltrichloroethane
      (DDT), and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), are associated with a
      variety of adverse health effects in organisms or progeny by altering the
      endocrine system. Environmental estrogens, including BPA, phthalates, and
      phytoestrogens, are the most extensively studied and are considered to mimic the
      actions of endogenous estrogen, 17beta-estradiol (E2). Diverse modes of action of
      estrogen and estrogen receptors (ERalpha and ERbeta) have been described, but the
      mode of action of estrogenic EDC is postulated to be more complex and needs to be
      more clearly elucidated. This review examines the adverse effects of estrogenic
      EDC on male or female reproductive systems and molecular mechanisms underlying
      EDC effects that modulate ER-mediated signaling. Mechanisms of action for
      estrogenic EDC may involve both ER-dependent and ER-independent pathways. Recent
      findings from systems toxicology of examining estrogenic EDC are also discussed. 

PMID- 24749481
TI  - Relationships of chemical concentrations in maternal and cord blood: a review of
      available data.
AB  - The developing fetus is likely to be exposed to the same environmental chemicals
      as the mother during critical periods of growth and development. The degree of
      maternal-fetal transfer of chemical compounds will be affected by chemical and
      physical properties such as lipophilicity, protein binding, and active transport
      mechanisms that influence absorption and distribution in maternal tissues.
      However, these transfer processes are not fully understood for most environmental
      chemicals. This review summarizes reported data from more than 100 studies on the
      ratios of cord:maternal blood concentrations for a range of chemicals including
      brominated flame-retardant compounds, polychlorinated biphenyls (PCB),
      polychlorinated dibenzodioxins and dibenzofurans, organochlorine pesticides,
      perfluorinated compounds, polyaromatic hydrocarbons, metals, and tobacco smoke
      components. The studies for the chemical classes represented suggest that
      chemicals frequently detected in maternal blood will also be detectable in cord
      blood. For most chemical classes, cord blood concentrations were found to be
      similar to or lower than those in maternal blood, with reported cord:maternal
      ratios generally between 0.1 and 1. Exceptions were observed for selected
      brominated flame-retardant compounds, polyaromatic hydrocarbons, and some metals,
      for which reported ratios were consistently greater than 1. Careful
      interpretation of the data in a risk assessment context is required because
      measured concentrations of environmental chemicals in cord blood (and thus the
      fetus) do not necessarily imply adverse effects or risk. Guidelines and
      recommendations for future cord:maternal blood biomonitoring studies are
      discussed. 

PMID- 24749482
TI  - Getting comfortable as "fish out of water": using qualitative research methods
      training to enhance the technical capacity of family therapy trainees.
AB  - This article describes a qualitative research methods training project undertaken
      in a COAMFTE-accredited family therapy master's-level program. Graduate students
      were trained to collect research data for a qualitative study on the resilience
      of families displaced to the United States because of war and politically
      motivated violence in their country of origin. By involving trainees in a
      research project with refugees, the project was intended to address a gap in
      clinicians' training, specific to the refugee population (Miller, Muzurovic,
      Worthington, Tipping, and Goldman, American Journal of Orthopsychiatry 2002; 72:
      341). However, the training process was also a way to increase the students'
      skills at interviewing in complex situations, develop their cultural sensitivity
      beyond awareness, enhance their capacity for routine self-reflection, and
      introduce them to basic practices of qualitative research methodology. In this
      article, we focus on the students' experience of the training and discuss the
      potential implications of their feedback for family therapy training. 

PMID- 24749483
TI  - Synthesis, redox properties, and electronic coupling in the diferrocene aza
      dipyrromethene and azaBODIPY donor-acceptor dyad with direct ferrocene-alpha
      pyrrole bond.
AB  - 3,3'-Diferrocenylazadipyrromethene (3) and corresponding difluoroboryl
      (azaBODIPY) complex (4) were synthesized in several steps from
      ferrocenecarbaldehyde, following the well-explored chalcone-type synthetic
      approach. The novel diiron complexes, in which ferrocene groups are directly
      connected to the alpha-pyrrolic positions were characterized by a variety of
      spectroscopic techniques, electrochemistry, spectroelectrochemistry, and X-ray
      crystallography, while their electronic structure, redox properties, and UV-vis
      spectra were correlated with the density functional theory (DFT) and time
      dependent DFT calculations. 

PMID- 24749484
TI  - Arabidopsis PTB1 and PTB2 proteins negatively regulate splicing of a mini-exon
      splicing reporter and affect alternative splicing of endogenous genes
      differentially.
AB  - This paper examines the function of Arabidopsis thaliana AtPTB1 and AtPTB2 as
      plant splicing factors. The effect on splicing of overexpression of AtPTB1 and
      AtPTB2 was analysed in an in vivo protoplast transient expression system with a
      novel mini-exon splicing reporter. A range of mutations in pyrimidine-rich
      sequences were compared with and without AtPTB and NpU2AF65 overexpression.
      Splicing analyses of constructs in protoplasts and RNA from overexpression lines
      used high-resolution reverse transcription polymerase chain reaction (RT-PCR).
      AtPTB1 and AtPTB2 reduced inclusion/splicing of the potato invertase mini-exon
      splicing reporter, indicating that these proteins can repress plant intron
      splicing. Mutation of the polypyrimidine tract and closely associated Cytosine
      and Uracil-rich (CU-rich) sequences, upstream of the mini-exon, altered
      repression by AtPTB1 and AtPTB2. Coexpression of a plant orthologue of U2AF65
      alleviated the splicing repression of AtPTB1. Mutation of a second CU-rich
      upstream of the mini-exon 3' splice site led to a decline in mini-exon splicing,
      indicating the presence of a splicing enhancer sequence. Finally, RT-PCR of AtPTB
      overexpression lines with c. 90 known alternative splicing (AS) events showed
      that AtPTBs significantly altered AS of over half the events. AtPTB1 and AtPTB2
      are splicing factors that influence alternative splicing. This occurs in the
      potato invertase mini-exon via the polypyrimidine tract and associated pyrimidine
      rich sequence.

PMID- 24749485
TI  - Mobility, satisfaction with functional capacity and perceived quality of life
      (PQOL) in older persons with self-reported visual impairment: the pathway between
      ability to get around and PQOL.
AB  - BACKGROUND: Research shows that ability to get around (AGA) is significantly
      associated with perceived quality of life (PQOL) among older persons with self
      reported visual impairment. Much of this impact, however, is through satisfaction
      with one's functional capacity. Satisfaction with functional capacity is a
      construct composed of five items: satisfaction with (1) activities of daily
      living, (2) capacity to work, (3) self, (4) health and (5) sleep. At present, it
      is not known how AGA interacts individually with these items to influence PQOL.
      PURPOSE: The purpose of this study is to investigate the extent to which AGA
      interacts with each of these five items to affect PQOL. METHODS: Structural
      equation modelling was employed in a secondary-analysis of data from 356 persons
      (aged 56-72) with self-reported visual impairment to identify the pathways by
      which AGA affects PQOL. RESULTS: Satisfaction with self and health were the only
      items found to be both directly related to QOL and to provide a significant
      pathway between AGA and PQOL. CONCLUSION: AGA significantly affects PQOL both
      directly and indirectly through its impact on people's satisfaction with self and
      health. Lessons may be learnt from this to better focus mobility interventions to
      enhance PQOL in this population.

PMID- 24749486
TI  - Validation of the Hungarian version of the Roland-Morris disability
      questionnaire.
AB  - PURPOSE: To create a cross-culturally adapted and clinically valid Hungarian
      version of the Roland-Morris Disability Questionnaire (RMQ). METHODS: After the
      translation and cross-cultural adaptation process, a total of 133 patients were
      included into the quality measurement study. Validity and reliability domains of
      the Hungarian RMQ were tested following the COSMIN guideline. Differences between
      clinically different patient groups were measured. Correlations of the RMQ with
      the Oswestry Disability Index (ODI), the World Health Organization Quality of
      Life-BREF assessment (WHOQoL) and pain were also calculated. To assess the
      reliability dimension, internal consistency (Cronbach's alpha) was determined and
      the test-retest method was used to calculate the interclass correlation
      coefficient (ICC), the standard error of measurement (SEM) and the minimal
      detectable change (MDC). RESULTS: Patients indicated for surgery or having
      neurological deficit had significantly higher RMQ scores. RMQ strongly correlated
      with pain (r = 0.61), ODI (r = 0.81) and physical subscale of WHOQoL (r = -0.7).
      Reliability of the Hungarian RMQ was expressed with a Cronbach's alpha of 0.87,
      ICC of 0.91 (p < 0.001) and SEM and MDC as 1.71 and 4.74 points, respectively.
      CONCLUSIONS: Translation and cross-cultural adaptation process of the RMQ into
      Hungarian language was successful resulting in a reliable and valid measurement
      tool with good psychometric properties. Implications for Rehabilitation Low back
      pain (LBP) related disability is a big health, social and economical problem in
      industrial countries. Correct evaluation of spine related disability can be
      performed using valid and reliable national versions of condition specific
      patient reported questionnaires such as the Roland-Morris Disability
      Questionnaire (RMQ). After the cross-cultural adaptation and validation of the
      Hungarian RMQ, it can be reliably used for the evaluation of LBP patients and for
      their follow-up during a rehabilitation process.

PMID- 24749487
TI  - A pseudo-penalized quasi-likelihood approach to the spatial misalignment problem
      with non-normal data.
AB  - Spatially referenced datasets arising from multiple sources are routinely
      combined to assess relationships among various outcomes and covariates. The
      geographical units associated with the data, such as the geographical coordinates
      or areal-level administrative units, are often spatially misaligned, that is,
      observed at different locations or aggregated over different geographical units.
      As a result, the covariate is often predicted at the locations where the response
      is observed. The method used to align disparate datasets must be accounted for
      when subsequently modeling the aligned data. Here we consider the case where
      kriging is used to align datasets in point-to-point and point-to-areal
      misalignment problems when the response variable is non-normally distributed. If
      the relationship is modeled using generalized linear models, the additional
      uncertainty induced from using the kriging mean as a covariate introduces a
      Berkson error structure. In this article, we develop a pseudo-penalized quasi
      likelihood algorithm to account for the additional uncertainty when estimating
      regression parameters and associated measures of uncertainty. The method is
      applied to a point-to-point example assessing the relationship between low-birth
      weights and PM2.5 levels after the onset of the largest wildfire in Florida
      history, the Bugaboo scrub fire. A point-to-areal misalignment problem is
      presented where the relationship between asthma events in Florida's counties and
      PM2.5 levels after the onset of the fire is assessed. Finally, the method is
      evaluated using a simulation study. Our results indicate the method performs well
      in terms of coverage for 95% confidence intervals and naive methods that ignore
      the additional uncertainty tend to underestimate the variability associated with
      parameter estimates. The underestimation is most profound in Poisson regression
      models.

PMID- 24749488
TI  - Real-time isothermal detection of Shiga toxin-producing Escherichia coli using
      recombinase polymerase amplification.
AB  - Shiga toxin-producing Escherichia coli (STEC) are a major family of foodborne
      pathogens of public health, zoonotic, and economic significance in the United
      States and worldwide. To date, there are no published reports on use of
      recombinase polymerase amplification (RPA) for STEC detection. The primary goal
      of this study was to assess the potential application of RPA in detection of
      STEC. This study focused on designing and evaluating RPA primers and fluorescent
      probes for isothermal (39 degrees C) detection of STEC. Compatible sets of
      candidate primers and probes were designed for detection of Shiga toxin 1 and 2
      (Stx1 and 2), respectively. The sets were evaluated for specificity and
      sensitivity against STEC (n=12) of various stx genotypes (stx1/stx2, stx1, or
      stx2, respectively), including non-Stx-producing E. coli (n=28) and other genera
      (n=7). The primers and probes that were designed targeted amplification of the
      subunit A moiety of stx1 and stx2. The assay detected STEC in real time (within 5
      10 min at 39 degrees C) with high sensitivity (93.5% vs. 90%; stx1 vs. stx2),
      specificity (99.1% vs. 100%; stx1 vs. stx2), and predictive value (97.9% for both
      stx1 vs. stx2). Limits of detection of ~ 5-50 colony-forming units/mL were
      achieved in serially diluted cultures grown in brain heart infusion broth. This
      study successfully demonstrated for the first time that RPA can be used for
      isothermal real-time detection of STEC.

PMID- 24749489
TI  - "PULSED" versus "CONTINUOUS" application of the prodrug 5-FC for enhancing
      oncolytic effectiveness of a measles vaccine virus armed with a suicide gene.
AB  - Oncolytic virotherapy with measles vaccine virus (MeV) already has been
      demonstrated to be safe. However, early clinical results pointed out the
      necessity for an enhancement of oncolytic effectiveness of MeV-based
      virotherapeutics. In our work, we are developing an armed measles vaccine virus
      (MeV-SCD) encoding a suicide fusion gene of yeast cytosine deaminase/uracil
      phosphoribosyltransferase, conveting the non-toxic prodrug 5-FC to the
      chemotherapeutic drug 5-FU. To pre-clinically investigate how an optimal prodrug
      assisted therapeutic regimen could look like, we added 5-FC at different time
      points after infection with MeV-SCD and either let the prodrug remain in the
      tumor cell culture medium continuously for different time periods ("continuous" 5
      FC application) or applied it only temporarily for defined shorter periods of
      time ("pulsed" 5-FC application); we also varied the time point at which 5-FC was
      added after infection with MeV-SCD. As a result, addition of the prodrug at early
      times post infection (e.g., at 3 hpi) was found to be inferior concerning the
      overall oncolytic effectiveness when compared with addition of 5-FC at later time
      points (e.g., at 24 hpi). Next, oncolytic effectiveness was found to correlate
      positively with the overall duration of incubation of MeV-infected tumor cells
      with 5-FC. Of note, this was true despite our finding that addition of the
      prodrug could also exert an inhibitory effect on the generation of infectious
      progeny virus particles, i.e. on virus replication. These findings should be
      helpful for the rational design of further trials (preclinical, clinical) using
      suicide gene armed virotherapeutics, such as MeV-SCD.

PMID- 24749490
TI  - Breaking good: the inexorable rise of BTK inhibitors in the treatment of chronic
      lymphocytic leukaemia.
AB  - Although expressed in several haematological lineages and involved in multiple
      different signalling pathways, Bruton tyrosine kinase (BTK) plays an
      indispensible role in B cells in signalling from the B cell receptor (BCR) for
      antigen. Many B cell malignancies remain dependent on constitutive BCR
      signalling, making BTK a functional therapeutic target. Several BTK inhibitors
      (BTKi) with different kinomes and modes of action are being assessed clinically.
      This review documents the efficacy and toxicity of BTKi in chronic lymphocytic
      leukaemia (CLL). Clinically, the furthest in development is ibrutinib (trade
      name, Imbruvica), an irreversible BTKi, which has shown spectacular preliminary
      efficacy, with rapid reductions in lymph nodes accompanied by peripheral blood
      lymphocytosis. The lymphocytosis resolves slowly and most patients do not enter a
      complete remission. Nevertheless, it is possible to maintain many CLL patients,
      even those with adverse cytogenetic features, on drug for many months with
      minimal toxicities, thus potentially transforming the therapeutic paradigms for
      CLL. The efficacy, lack of toxicity and oral administration of BTKi will ensure
      their adoption in a wide range of B cell malignancies. An outstanding challenge
      is to incorporate BTKi with other precision medicines in a mechanism-based manner
      in order to dispense with conventional chemotherapy. 

PMID- 24749491
TI  - Radiographic evaluation of femoral torsion and correlation with computed
      tomographic techniques in labrador retrievers with and without cranial cruciate
      ligament disease.
AB  - OBJECTIVES: To (1) develop a technique to determine the anteversion angle (AA) of
      the femur on a single radiograph; (2) determine the correlation between this
      technique and other published radiographic and computed tomographic (CT) methods;
      and (3) compare the diagnostic outcome of these methods in determining the level
      at which femoral torsion occurred in Labrador Retrievers with cranial cruciate
      ligament (CCL) deficiency. STUDY DESIGN: Cross-sectional clinical study. ANIMALS:
      Mature pure-bred Labrador Retrievers (n = 30). METHODS: Pelvic limbs (n = 28) of
      14 dogs without CCL deficiency were classified as control, whereas limbs of 16
      dogs (18 limbs) with CCL deficiency were considered as diseased. Femoral torsion
      was evaluated using radiography and CT and variables were compared among limb
      groups by use of a mixed-model ANOVA, with P < .05 considered significant.
      RESULTS: There was a significant association between biplanar and lateral plane
      AAs but neither correlated with CT assessment of femoral torsion. On CT, a
      significant correlation was identified between overall AA and each of the distal,
      proximal, and femoral head trochanteric angles. Biplanar and lateral plane AAs
      did not differ between normal and CCL deficient limbs. On CT, overall and distal
      AAs were increased in CCL deficient limbs compared to control. CONCLUSION:
      Biplanar determination of femoral torsion can be estimated based on a single
      lateral radiograph but the results will be inaccurate as only CT identified and
      localized the site of femoral torsion.

PMID- 24749492
TI  - Intranasal delivery of FSD-C10, a novel Rho kinase inhibitor, exhibits
      therapeutic potential in experimental autoimmune encephalomyelitis.
AB  - Viewing multiple sclerosis (MS) as both neuroinflammation and neurodegeneration
      has major implications for therapy, with neuroprotection and neurorepair needed
      in addition to controlling neuroinflammation in the central nervous system (CNS).
      While Fasudil, an inhibitor of Rho kinase (ROCK), is known to suppress
      experimental autoimmune encephalomyelitis (EAE), an animal model of MS, it relies
      on multiple, short-term injections, with a narrow safety window. In this study,
      we explored the therapeutic effect of a novel ROCK inhibitor FSD-C10, a Fasudil
      derivative, on EAE. An important advantage of this derivative is that it can be
      used via non-injection routes; intranasal delivery is the preferred route because
      of its efficient CNS delivery and the much lower dose compared with oral
      delivery. Our results showed that intranasal delivery of FSD-C10 effectively
      ameliorated the clinical severity of EAE and CNS inflammatory infiltration and
      promoted neuroprotection. FSD-C10 effectively induced CNS production of the
      immunoregulatory cytokine interleukin-10 and boosted expression of nerve growth
      factor and brain-derived neurotrophic factor proteins, while inhibiting
      activation of p-nuclear factor-kappaB/p65 on astrocytes and production of
      multiple pro-inflammatory cytokines. In addition, FSD-C10 treatment effectively
      induced CD4(+) CD25(+) , CD4(+) FOXP3(+) regulatory T cells. Together, our
      results demonstrate that intranasal delivery of the novel ROCK inhibitor FSD-C10
      has therapeutic potential in EAE, through mechanisms that possibly involve both
      inhibiting CNS inflammation and promoting neuroprotection.

PMID- 24749493
TI  - Functional hierarchy of herpes simplex virus type-1 membrane proteins in corneal
      infection and virus transmission to ganglionic neurons.
AB  - PURPOSE: To determine the relative importance of viral glycoproteins gK, gM, gE
      and the membrane protein UL11 in infection of mouse corneas and ganglionic
      neurons. METHODS: Mouse eyes were scarified and infected with herpes simplex
      virus (HSV)-1(F), gE-null, gM-null, gK-null, or UL11-null viruses. Clinical signs
      of ocular disease were monitored daily. Virus shedding was determined at 24, 48
      and 72 h post infection. Viral DNA within trigeminal ganglia (TG) was quantified
      by quantitative PCR at 30 d post infection. RESULTS: The gE-null virus replicated
      as efficiently as the parental virus and formed viral plaques approximately half
      the-size in comparison with the HSV-1(F) wild-type virus. The UL11-null and gM
      null viruses replicated approximately one log less efficiently than the wild-type
      virus, and formed plaques that were on average one-third the size and one-half
      the size of the wild-type virus, respectively. The gK-null virus replicated more
      than 3-logs less efficiently than the wild-type virus and formed very small
      plaques (5-10 cells). Mice infected with the wild-type virus exhibited mild
      clinical ocular symptoms, while mice infected with the mutant viruses did not
      show any significant ocular changes. The wild-type virus produced the highest
      virus shedding post infection followed by the gM-null, gE-null and UL11-null
      viruses, while no gK-null virus was detected at any time point. All TG collected
      from mice infected with the wild-type virus and 6-of-10 of TG retrieved from mice
      infected with the UL11-null virus contained high numbers of viral genomes. The gE
      null and gM-null-infected ganglia contained moderate-to-low number of viral
      genomes in 4-of-10 and 2-of-10 mice, respectively. No viral genomes were detected
      in ganglionic tissues obtained from gK-null eye infections. CONCLUSIONS: The
      results show that gK plays the most important role among gM, gE and UL11 in
      corneal and ganglionic infection in the mouse eye model.

PMID- 24749494
TI  - The alpha1B -adrenoceptor subtype mediates adrenergic vasoconstriction in mouse
      retinal arterioles with damaged endothelium.
AB  - BACKGROUND AND PURPOSE: The alpha1-adrenoceptor family plays a critical role in
      regulating ocular perfusion by mediating responses to catecholamines. The purpose
      of the present study was to determine the contribution of individual alpha1
      adrenoceptor subtypes to adrenergic vasoconstriction of retinal arterioles using
      gene-targeted mice deficient in one of the three adrenoceptor subtypes (alpha1A
      AR(-/-), alpha1B-AR(-/-) and alpha1D-AR(-/-) respectively). EXPERIMENTAL
      APPROACH: Using real-time PCR, mRNA expression for individual alpha1-adrenoceptor
      subtypes was determined in murine retinal arterioles. To assess the functional
      relevance of the three alpha1-adrenoceptor subtypes for mediating vascular
      responses, retinal vascular preparations from wild-type mice and mice deficient
      in individual alpha1-adrenoceptor subtypes were studied in vitro using video
      microscopy. KEY RESULTS: Retinal arterioles expressed mRNA for all three alpha1
      adrenoceptor subtypes. In functional studies, arterioles from wild-type mice with
      intact endothelium responded only negligibly to the alpha1-adrenoceptor agonist
      phenylephrine. In endothelium-damaged arterioles from wild-type mice,
      phenylephrine evoked concentration-dependent constriction that was attenuated by
      the alpha1-adrenoceptor blocker prazosin. Strikingly, phenylephrine only
      minimally constricted endothelium-damaged retinal arterioles from alpha1B-AR(-/-)
      mice, whereas arterioles from alpha1A -AR(-/-) and alpha1D-AR(-/-) mice
      constricted similarly to arterioles from wild-type mice. Constriction to U46619
      was similar in endothelium-damaged retinal arterioles from all four mouse
      genotypes. CONCLUSIONS AND IMPLICATIONS: The present study is the first to
      demonstrate that alpha1-adrenoceptor-mediated vasoconstriction in murine retinal
      arterioles is buffered by the endothelium. When the endothelium is damaged, a
      vasoconstricting role of the alpha1B-adrenoceptor subtype is unveiled. Hence, the
      alpha1B-adrenoceptor may represent a target to selectively modulate retinal blood
      flow in ocular diseases associated with endothelial dysfunction.

PMID- 24749495
TI  - The dynamics of herpesvirus reactivations during and after severe drug eruptions:
      their relation to the clinical phenotype and therapeutic outcome.
AB  - BACKGROUND: Drug-induced hypersensitivity syndrome/drug rash with eosinophilia
      and systemic symptoms (DIHS/DRESS) and Stevens-Johnson syndrome (SJS)/toxic
      epidermal necrolysis (TEN) represent contrasting poles of severe drug eruptions,
      and sequential reactivations of several herpesviruses have exclusively been
      demonstrated in the former. No previous studies, however, were extended beyond
      the acute stage. We sought to investigate whether herpesvirus reactivations could
      also be observed in SJS/TEN and beyond the acute stage of both diseases. METHODS:
      Patients with SJS (n = 16), SJS/TEN overlap (n = 2), TEN (n = 10), and DIHS/DRESS
      (n = 34) were enrolled. We performed a retrospective analysis of Epstein-Barr
      virus (EBV), human herpesvirus 6 (HHV-6), and cytomegalovirus (CMV) DNA loads
      sequentially determined by real-time polymerase chain reaction during a 2-year
      period after onset. RESULTS: Persistently increased EBV loads were detected in
      SJS during the acute stage and long after resolution, but not in others. In
      contrast, high HHV-6 loads were exclusively detected in DIHS/DRESS during the
      acute stage. The dynamics of herpesvirus reactivation varied in DIHS/DRESS
      according to the use of systemic corticosteroids: While EBV loads were higher in
      patients not receiving systemic corticosteroids, CMV and HHV-6 loads were higher
      in those receiving them. CONCLUSIONS: Distinct patterns of herpesvirus
      reactivation according to the pathological phenotype and to the use of systemic
      corticosteroids were observed during the acute stage and follow-up period, which
      may contribute, at least in part, to the difference in the clinical
      manifestations and long-term outcomes. Systemic corticosteroids during the acute
      stage may improve the outcomes in DIHS/DRESS.

PMID- 24749496
TI  - Quantitative comparison of cortical and deep grey matter in pathological subtypes
      of unilateral cerebral palsy.
AB  - AIM: The aim of this study was to quantify grey matter changes in children with
      unilateral cerebral palsy (UCP), differentiating between cortical or deep grey
      matter (CDGM) lesions, periventricular white matter (PWM) lesions, and unilateral
      and bilateral lesions. METHOD: In a cross-sectional study we obtained high
      resolution structural magnetic resonance images from 72 children (41 males, 31
      females, mean age 10y 9mo [SD 3y 1mo], range 5y 1mo-17y 1mo) with UCP (33 left,
      39 right hemiplegia; Manual Ability Classification System level I n=29, II n=43;
      Gross Motor Function Classification System level I n=46, II n=26), and 19
      children with typical development (CTD; eight males, 11 females, mean age 11y 2mo
      [SD 2y 7mo], range 7y 8mo-16y 4mo). Images were classified by lesion type and
      analyzed using voxel-based morphometry (VBM) and subcortical volumetric analysis.
      RESULTS: Deep grey matter volumes were not significantly different between
      children with CDGM and PWM lesions, with the thalamus, putamen, and globus
      pallidus being reduced unilaterally in both groups compared with CTD (p<=0.001).
      Children with CDGM lesions additionally showed widespread cortical changes
      involving all lobes using VBM (p<0.01). Children with bilateral lesions had
      reduced thalamus and putamen volumes bilaterally (p<0.001). The thalamic volume
      was reduced bilaterally in children with unilateral lesions (p=0.004).
      INTERPRETATION: Lesions to the PWM cause secondary changes to the deep grey
      matter structures similar to primary changes seen in CDGM lesions. Despite having
      a unilateral phenotype, grey matter changes are observed bilaterally, even in
      children with unilateral lesions.

PMID- 24749497
TI  - Accounting for genetic and environmental confounds in associations between parent
      and child characteristics: a systematic review of children-of-twins studies.
AB  - Parental psychopathology, parenting style, and the quality of intrafamilial
      relationships are all associated with child mental health outcomes. However, most
      research can say little about the causal pathways underlying these associations.
      This is because most studies are not genetically informative and are therefore
      not able to account for the possibility that associations are confounded by gene
      environment correlation. That is, biological parents not only provide a rearing
      environment for their child, but also contribute 50% of their genes. Any
      associations between parental phenotype and child phenotype are therefore
      potentially confounded. One technique for disentangling genetic from
      environmental effects is the children-of-twins (COT) method. This involves using
      data sets comprising twin parents and their children to distinguish genetic from
      environmental associations between parent and child phenotypes. The COT technique
      has grown in popularity in the last decade, and we predict that this surge in
      popularity will continue. In the present article we explain the COT method for
      those unfamiliar with its use. We present the logic underlying this approach,
      discuss strengths and weaknesses, and highlight important methodological
      considerations for researchers interested in the COT method. We also cover
      variations on basic COT approaches, including the extended-COT method, capable of
      distinguishing forms of gene-environment correlation. We then present a
      systematic review of all the behavioral COT studies published to date. These
      studies cover such diverse phenotypes as psychosis, substance abuse,
      internalizing, externalizing, parenting, and marital difficulties. In reviewing
      this literature, we highlight past applications, identify emergent patterns, and
      suggest avenues for future research.

PMID- 24749498
TI  - Complex haemostatic abnormalities as a cause of bleeding after neurosurgery in a
      patient with Gaucher disease.
AB  - We report a treatment-naive patient with Gaucher disease (GD) who experienced
      repeated bleeding after three neurosurgeries for a brain tumour, identified as an
      oligoastrocytoma. The patient had normal values on basic haemostatic tests:
      prothrombin time, 75-105%; activated partial thromboplastin time, 30.3-34 s; and
      mild thrombocytopaenia, 96-115 * 10(9 )cells/l. However, additional tests showed
      mild von Willebrand factor (vWF) deficiency (vWF antigen, 56%; vWF ristocetin
      cofactor, 49%; factor VIII [FVIII], 54%) and abnormal collagen-mediated platelet
      aggregation (0.45-0.55). Bleeding control was achieved after vWF/FVIII
      concentrate and platelet transfusions. This case raises questions about the safe
      platelet count and basic haemostatic tests for assessing bleeding risk in
      patients with GD prior to surgery. In patients with GD, a minimum haemostatic
      evaluation should include platelet count and basic haemostatic tests such as
      fibrinogen, prothrombin time, activated partial thromboplastin time as well as
      platelet function tests and assessing vWF and FVIII levels. Specific coagulation
      factors or platelet function deficiencies should be corrected with factor
      concentrates or platelet transfusions. 

PMID- 24749499
TI  - Equality for all? White Americans' willingness to address inequality with Asian
      and African Americans.
AB  - White Americans' willingness to engage in dialogues about intergroup
      commonalities and power inequalities with Asian and African Americans were
      examined in two experiments. Because Whites perceive that African Americans
      experience greater discrimination than do Asian Americans, we predicted that they
      would be more willing to engage in dialogues that would interrogate injustice and
      inequality with them. We also explored the role of common in-group identity (as
      Americans) on willingness for dialogue about inequality. In both studies, Whites
      were less interested in engaging in power talk with Asian Americans than with
      African Americans, but the difference in willingness for commonality talk was
      smaller. Asian Americans were perceived as experiencing lower levels of
      discrimination (Studies 1 and 2) and identify less with America (Study 2) both of
      which predicted lower willingness for power talk with them. Common in-group
      identity manipulations had marginal effects on willingness for power talk with
      African Americans and no effect on power talk with Asian Americans. Implications
      for improving social disparities between various groups were discussed.

PMID- 24749500
TI  - Domestication and diversification: a comparative analysis of the play fighting of
      the Brown Norway, Sprague-Dawley, and Wistar laboratory strains of (Rattus
      norvegicus).
AB  - Laboratory strains of rats are a commonly used subject to study play behavior.
      Recent research has shown that play in one laboratory strain of rat (e.g., Long
      Evans hooded) differs in a number of ways from its wild counterparts. These
      findings suggest that domestication affects some aspects of play behavior.
      However, there are multiple strains of laboratory rats, which have been
      domesticated through different lineages all derived from wild rats and it cannot
      be assumed that all domestic strains are identical in their play. Therefore, the
      aim of this study was to compare the play behavior of three other strains of
      laboratory rats (e.g., Wistar, Sprague-Dawley, and Brown Norway). All strains
      were similar to each other as they all engaged in high frequencies of play,
      tolerated similar interanimal distances before initiating playful defense and
      displayed similar acrobatic capacities, suggesting domestication produces some
      common changes in play and other factors that influence play. However, strains
      differed significantly from one another in the use of tactics that promote bodily
      contact during play. Indeed, in this regard, some strains were more similar to
      wild rats than others, suggesting that some domestication-induced changes are
      either unique or more prominent in some laboratory strains than others. Such a
      mosaic pattern of transformation not only offers the possibility of using strain
      differences to characterize the genetic factors contributing to different facets
      of play, but also cautions researchers from making rat-general conclusions from
      studies on any one strain.

PMID- 24749501
TI  - Relative quantity judgments between discrete spatial arrays by chimpanzees (Pan
      troglodytes) and New Zealand robins (Petroica longipes).
AB  - Quantity discrimination for items spread across spatial arrays was investigated
      in chimpanzees (Pan troglodytes) and North Island New Zealand robins (Petroica
      longipes), with the aim of examining the role of spatial separation on the
      ability of these 2 species to sum and compare nonvisible quantities which are
      both temporally and spatially separated, and to assess the likely mechanism
      supporting such summation performance. Birds and chimpanzees compared 2 sets of
      discrete quantities of items that differed in number. Six quantity comparisons
      were presented to both species: 1v2, 1v3, 1v5, 2v3, 2v4, and 2v5. Each was
      distributed 1 at a time across 2 7-location arrays. Every individual item was
      viewed 1 at a time and hidden, with no more than a single item in each location
      of an array, in contrast to a format where all items were placed together into 2
      single locations. Subjects responded by selecting 1 of the 2 arrays and received
      the entire quantity of food items hidden within that array. Both species
      performed better than chance levels. The ratio of items between sets was a
      significant predictor of performance in the chimpanzees, but it was not
      significant for robins. Instead, the absolute value of the smaller quantity of
      items presented was the significant factor in robin responses. These results
      suggest a species difference for this task when considering various dimensions
      such as ratio or total number of items in quantity comparisons distributed across
      discrete 7-location arrays.

PMID- 24749502
TI  - Navigation with two landmarks in rats (Rattus norvegicus): the role of landmark
      salience.
AB  - In two experiments, male and female rats were trained in a Morris pool in the
      presence of 1 (Experiment 1) or 2 (Experiment 2) landmarks, which were placed
      relatively close in relation to a hidden platform. Experiment 1 established the
      relative salience of 3 landmarks. Two of them revealed a similar salience, and
      smaller than a third one, the most salient landmark, both in training and on a
      test trial without the platform. Then in Experiment 2 rats were extensively
      trained to find a hidden platform in the presence of a configuration formed by 2
      landmarks and the effects of varying the salience of one of the landmarks were
      studied. Subsequent test trials without the platform revealed that finding the
      platform was controlled by different strategies and that the rats were taking
      advantage of this redundancy depending on the nature of the test trials.
      Surprisingly, in Experiment 2 a clear sex difference was found on escape trials
      only, with males reaching the platform faster than females.

PMID- 24749503
TI  - Social environment elicits lateralized behaviors in gorillas (Gorilla gorilla
      gorilla) and chimpanzees (Pan troglodytes).
AB  - The influence of the social environment on lateralized behaviors has now been
      investigated across a wide variety of animal species. New evidence suggests that
      the social environment can modulate behavior. Currently, there is a paucity of
      data relating to how primates navigate their environmental space, and
      investigations that consider the naturalistic context of the individual are few
      and fragmented. Moreover, there are competing theories about whether only the
      right or rather both cerebral hemispheres are involved in the processing of
      social stimuli, especially in emotion processing. Here we provide the first
      report of lateralized social behaviors elicited by great apes. We employed a
      continuous focal animal sampling method to record the spontaneous interactions of
      a captive zoo-living colony of chimpanzees (Pan troglodytes) and a biological
      family group of peer-reared western lowland gorillas (Gorilla gorilla gorilla).
      We specifically focused on which side of the body (i.e., front, rear, left,
      right) the focal individual preferred to keep conspecifics. Utilizing a newly
      developed quantitative corpus-coding scheme, analysis revealed both chimpanzees
      and gorillas demonstrated a significant group-level preference for focal
      individuals to keep conspecifics positioned to the front of them compared with
      behind them. More interestingly, both groups also manifested a population-level
      bias to keep conspecifics on their left side compared with their right side. Our
      findings suggest a social processing dominance of the right hemisphere for
      context-specific social environments. Results are discussed in light of the
      evolutionary adaptive value of social stimulus as a triggering factor for the
      manifestation of group-level lateralized behaviors.

PMID- 24749504
TI  - A working memory account of the interaction between numbers and spatial
      attention.
AB  - Rather than reflecting the long-term memory construct of a mental number line, it
      has been proposed that the relation between numbers and space is of a more
      temporary nature and constructed in working memory during task execution. In
      three experiments we further explored the viability of this working memory
      account. Participants performed a speeded dot detection task with dots appearing
      left or right, while maintaining digits or letters in working memory. Just before
      presentation of the dot, these digits or letters were used as central cues. These
      experiments show that the "attentional SNARC-effect" (where SNARC is the spatial
      numerical association of response codes) is not observed when only the lastly
      perceived number cue--and no serially ordered sequence of cues--is maintained in
      working memory (Experiment 1). It is only when multiple items (numbers in
      Experiment 2; letters in Experiment 3) are stored in working memory in a serially
      organized way that the attentional cueing effect is observed as a function of
      serial working memory position. These observations suggest that the "attentional
      SNARC-effect" is strongly working memory based. Implications for theories on the
      mental representation of numbers are discussed.

PMID- 24749505
TI  - Cell and gene therapy for Friedreich ataxia: progress to date.
AB  - Neurodegenerative disorders such as Friedreich ataxia (FRDA) present significant
      challenges in developing effective therapeutic intervention. Current treatments
      aim to manage symptoms and thus improve quality of life, but none can cure, nor
      are proven to slow, the neurodegeneration inherent to this disease. The primary
      clinical features of FRDA include progressive ataxia and shortened life span,
      with complications of cardiomyopathy being the major cause of death. FRDA is most
      commonly caused by an expanded GAA trinucleotide repeat in the first intron of
      FXN that leads to reduced levels of frataxin, a mitochondrial protein important
      for iron metabolism. The GAA expansion in FRDA does not alter the coding sequence
      of FXN. It results in reduced production of structurally normal frataxin, and
      hence any increase in protein level is expected to be therapeutically beneficial.
      Recently, there has been increased interest in developing novel therapeutic
      applications like cell and/or gene therapies, and these cutting-edge applications
      could provide effective treatment options for FRDA. Importantly, since
      individuals with FRDA produce frataxin at low levels, increased expression should
      not elicit an immune response. Here we review the advances to date and highlight
      the future potential for cell and gene therapy to treat this debilitating
      disease.

PMID- 24749506
TI  - Density and duration of pneumococcal carriage is maintained by transforming
      growth factor beta1 and T regulatory cells.
AB  - RATIONALE: Nasopharyngeal carriage of Streptococcus pneumoniae is a prerequisite
      for invasive disease, but the majority of carriage episodes are asymptomatic and
      self-resolving. Interactions determining the development of carriage versus
      invasive disease are poorly understood but will influence the effectiveness of
      vaccines or therapeutics that disrupt nasal colonization. OBJECTIVES: We sought
      to elucidate immunological mechanisms underlying noninvasive pneumococcal
      nasopharyngeal carriage. METHODS: Pneumococcal interactions with human
      nasopharyngeal and bronchial fibroblasts and epithelial cells were investigated
      in vitro. A murine model of nasopharyngeal carriage and an experimental human
      pneumococcal challenge model were used to characterize immune responses in the
      airways during carriage. MEASUREMENTS AND MAIN RESULTS: We describe the
      previously unknown immunological basis of noninvasive carriage and highlight
      mechanisms whose perturbation may lead to invasive disease. We identify the
      induction of active transforming growth factor (TGF)-beta1 by S. pneumoniae in
      human host cells and highlight the key role for TGF-beta1 and T regulatory cells
      in the establishment and maintenance of nasopharyngeal carriage in mice and
      humans. We identify the ability of pneumococci to drive TGF-beta1 production from
      nasopharyngeal cells in vivo and show that an immune tolerance profile,
      characterized by elevated TGF-beta1 and high nasopharyngeal T regulatory cell
      numbers, is crucial for prolonged carriage of pneumococci. Blockade of TGF-beta1
      signaling prevents prolonged carriage and leads to clearance of pneumococci from
      the nasopharynx. CONCLUSIONS: These data explain the mechanisms by which S.
      pneumoniae colonize the human nasopharynx without inducing damaging host
      inflammation and provide insight into the role of bacterial and host constituents
      that allow and maintain carriage.

PMID- 24749507
TI  - Peripapillary retinal nerve fiber layer changes in asymptomatic essential
      thrombocythemia patients.
AB  - PURPOSE: To investigate peripapillary retinal nerve fiber layer (RNFL) changes
      using optical coherence tomography (OCT) in patients with asymptomatic essential
      thrombocythemia (ET). MATERIALS AND METHODS: A consecutive case-control series of
      30 patients with asymptomatic ET and age-similar, gender, refractive error, race
      matched controls underwent a comprehensive eye examination and OCT of the
      peripapillary RNFL. Subjects with glaucoma, diabetes mellitus, hemoglobinopaties
      or other ocular diseases and those who underwent any retinal treatment were
      excluded. Inferior, superior, nasal and temporal peripapillary RNFL thicknesses
      were analyzed. One randomly selected eye per subject was compared with those of
      healthy ones. RESULTS: In the ET patients, the peripapillary RNFL thickness was
      particularly thin at the temporal quadrant (61.38 +/- 9.82 MUm, mean +/- SD), and
      the difference was statistically significant (p = 0.036) when compared with the
      control group (71.24 +/- 10.28 MUm). The average RNFL thickness was 88.73 +/-
      12.26 MUm in the ET patients and 96.91 +/- 13.66 MUm in the control group.
      Although the difference was not statistically significant (p = 0.226), the
      average RNFL was 8.44% thinner in ET patients than in healthy subjects.
      CONCLUSIONS: Asymptomatic ET patients may have peripapillary RNFL thinning as a
      result of their systemic illness. This study is the first to demonstrate
      peripapillary RFNL changes in asymptomatic ET patients.

PMID- 24749508
TI  - Collective cell migration: "all for one and one for all".
AB  - Cell migration is a key mechanism during neural development, as it allows cells
      to reach their final destination from their birthplace. In some cases, cells
      migrate in isolation, whereas in others they migrate in collectives, as chains,
      streams, clusters, or sheets. The coordinated and timely process of collective
      migration eventually ensures the proper organization of the nervous system and
      its misregulation leads to severe diseases, including neurological disorders.
      This review impinges upon the cellular and molecular interactions underlying
      collective cell migration in animal models, and highlights the recent advances
      made through in vivo analyses of the Drosophila wing glia.

PMID- 24749510
TI  - Monoclonal antibodies currently in Phase II and III trials for multiple myeloma.
AB  - INTRODUCTION: Despite the introduction of novel agents, such as thalidomide,
      lenalidomide and bortezomib, multiple myeloma (MM) remains an incurable disease
      and new therapies are needed. mAbs are a new promising anticancer treatment
      option. AREAS COVERED: This review will focus on mAbs that are currently under
      evaluation in Phase II and III clinical trials, as single agent and in
      combination with established treatment options. EXPERT OPINION: mAbs are a new
      strategy against MM, and they have demonstrated encouraging results in
      preclinical models. mAbs have a relatively benign side-effect profile and work
      synergistically with traditional chemotherapies and with immunomodulatory drugs
      and proteasome inhibitors.

PMID- 24749511
TI  - Single-molecule magnetism in a family of {Co(III)2Dy(III)2} butterfly complexes:
      effects of ligand replacement on the dynamics of magnetic relaxation.
AB  - The synthesis and structural characterization of four related heterometallic
      complexes of formulas
      [Dy(III)2Co(III)2(OMe)2(teaH)2(O2CPh)4(MeOH)4](NO3)2.MeOH.H2O (1a) and
      [Dy(III)2Co(III)2(OMe)2(teaH)2(O2CPh)4(MeOH)2(NO3)2].MeOH.H2O (1b),
      [Dy(III)2Co(III)2(OMe)2(dea)2(O2CPh)4(MeOH)4](NO3)2 (2),
      [Dy(III)2Co(III)2(OMe)2(mdea)2(O2CPh)4(NO3)2] (3), and
      [Dy(III)2Co(III)2(OMe)2(bdea)2(O2CPh)4(MeOH)4](NO3)2.0.5MeOH.H2O (4a) and
      [Dy(III)2Co(III)2(OMe)2(bdea)2(O2CPh)4(MeOH)2(NO3)2].MeOH.1.5H2O (4b) are
      reported (teaH3 = triethanolamine, deaH2 = diethanolamine, mdeaH2 = N
      methyldiethanolamine, and bdeaH2 = N-n-butyldiethanolamine). Compounds 1 (= 1a
      and 1b) and 4 (= 4a and 4b) both display two unique molecules within the same
      crystal and all compounds display a butterfly type core, with the Dy(III) ions
      occupying the central body positions and the diamagnetic Co(III) ions the outer
      wing-tip sites. Compounds 1-4 were investigated via direct current and
      alternating current magnetic susceptibility measurements, and it was found that
      each complex displayed single-molecule magnet (SMM) behavior. All four compounds
      display unique coordination and geometric environments around the Dy(III) ions
      and it was found that each displays a different anisotropy barrier. Ab initio
      calculations were performed on 1-4 and these determined the low lying electronic
      structure of each Dy(III) ion and the magnetic interactions for each cluster. It
      was found that there was a strong correlation between the calculated energy gap
      between the ground and first excited states of the single-ion ligand-field split
      Dy(III) levels and the experimentally observed anisotropy barrier. Furthermore,
      the transverse g factors found for the Dy(III) ions, defining the tunnelling
      rates within the ground Kramers doublets, are largest for 1, which agrees with
      the experimental observation of the shortest relaxation time in the high
      temperature domain for this complex. The magnetic exchange between the Dy(III)
      ions revealed overall antiferromagnetic interactions for each compound, derived
      from the dominant dipolar exchange resulting in nonmagnetic ground states for 1
      4. The diamagnetic ground states coupled with small tunneling gaps resulted in
      quantum tunneling time scales at zero field of between 0.1 and >1.5 s. 

PMID- 24749509
TI  - Microenvironmental regulation of telomerase isoforms in human embryonic stem
      cells.
AB  - Recent evidence points to extra-telomeric, noncanonical roles for telomerase in
      regulating stem cell function. In this study, human embryonic stem cells (hESCs)
      were cultured in 20% or 2% O2 microenvironments for up to 5 days and evaluated
      for telomerase reverse transcriptase (TERT) expression and telomerase activity.
      Results showed increased cell survival and maintenance of the undifferentiated
      state with elevated levels of nuclear TERT in 2% O2-cultured hESCs despite no
      significant difference in telomerase activity compared with their high-O2
      cultured counterparts. Pharmacological inhibition of telomerase activity using a
      synthetic tea catechin resulted in spontaneous hESC differentiation, while
      telomerase inhibition with a phosphorothioate oligonucleotide telomere mimic did
      not. Reverse transcription polymerase chain reaction (RT-PCR) analysis revealed
      variations in transcript levels of full-length and alternate splice variants of
      TERT in hESCs cultured under varying O2 atmospheres. Steric-blocking of
      Deltaalpha and Deltabeta hTERT splicing using morpholino oligonucleotides altered
      the hTERT splicing pattern and rapidly induced spontaneous hESC differentiation
      that appeared biased toward endomesodermal and neuroectodermal cell fates,
      respectively. Together, these results suggest that post-transcriptional
      regulation of TERT under varying O2 microenvironments may help regulate hESC
      survival, self-renewal, and differentiation capabilities through expression of
      extra-telomeric telomerase isoforms. 

PMID- 24749512
TI  - Skeletal cubic, lamellar, and ribbon phases of bundled thermotropic
      bolapolyphiles.
AB  - A series of T-shaped polyphilic molecules composed of a rigid linear biphenyl
      core with a polar glycerol group at each end and one swallow-tail
      semiperfluorinated lateral chain were synthesized and their thermotropic liquid
      crystalline (LC) phases were investigated by X-ray diffraction, calorimetry, and
      microscopy. The compounds have a long alkyl spacer between the aromatic core and
      the fluorinated C(n)F(2n+1) ends, where n = 4, 6, 8, and 10. Upon melting, all
      compounds start with lamellar LC phases, followed on heating by a rectangular
      columnar ribbon phase with c2mm symmetry. Unusually, a ribbon is a flat bundle of
      molecular cores highly aligned parallel to the ribbon axis. On further heating,
      for n = 8 and 10, this phase is succeeded by a bicontinuous cubic phase with Ia3d
      symmetry. This is a new variant of the "gyroid" phase, with axially oriented rod
      like molecular cores forming the skeleton of the two infinite networks and
      junctions separated by exactly two molecular lengths. In this tricontinuous core
      shell structure (aromatic-aliphatic-perfluoroalkyl), the polar glycerol domains
      of appreciable size, contained within the skeleton, can be considered as
      micellar.

PMID- 24749513
TI  - Transparent slippery surfaces made with sustainable porous cellulose lauroyl
      ester films.
AB  - In recent years, liquid repellent surfaces have attracted considerable attention
      because of their wide array of potential applications. In the present study,
      slippery surfaces were fabricated using novel sustainable, nanoporous cellulose
      lauroyl ester (CLE) films and slippery lubrication fluid. The nanoporous CLE
      films were obtained after spray-coating target surfaces using a nanoparticle
      suspension of CLE that was prepared via nanoprecipitation. After the deposition
      of the slippery liquid within the porous network, the obtained slippery surfaces
      exhibit both excellent liquid repellency upon liquid impact and anti-icing
      properties (by significantly retarding the icing time). Three-dimensional droplet
      manipulation was also achieved on these surfaces by taking advantage of the
      materials' low contact angle hysteresis and low adhesion property. 

PMID- 24749515
TI  - Depression, relationship quality, and couples' demand/withdraw and demand/submit
      sequential interactions.
AB  - This study investigated the associations among depression, relationship quality,
      and demand/withdraw and demand/submit behavior in couples' conflict interactions.
      Two 10-min conflict interactions were coded for each couple (N = 97) using
      Structural Analysis of Social Behavior (SASB; Benjamin, 1979a, 1987, 2000a).
      Depression was assessed categorically (via the presence of depressive disorders)
      and dimensionally (via symptom reports). Results revealed that relationship
      quality was negatively associated with demanding behavior, as well as receiving
      submissive or withdrawing behavior from one's partner. Relationship quality was
      positively associated with withdrawal. Demanding behavior was positively
      associated with women's depression symptoms but negatively associated with men's
      depression symptoms. Sequential analysis revealed couples' behavior was highly
      stable across time. Initiation of demand/withdraw and demand/submit sequences
      were negatively associated with partners' relationship adjustment. Female
      demand/male withdraw was positively associated with men's depression diagnosis.
      Results underscore the importance of sequential analysis when investigating
      associations among depression, relationship quality, and couples' interpersonal
      behavior.

PMID- 24749516
TI  - Editorial: New horizon in the treatment of hypertension--role for Ca channel
      blockers--why do Ca channel blockers be focused on?

PMID- 24749517
TI  - Mechanistic view of renal protective action of calcium channel blockade.
AB  - Calcium channel blockers are one of the most useful antihypertensive agents
      because of their definite blood pressure lowering action. Although the
      antihypertensive effect of calcium channel blockers is attributed predominantly
      to the blockade of L-type calcium channels, recent studies demonstrate that the
      blockade of other subtypes of calcium channels, including T-type and N-type
      calcium channels, offers renal protective action because of their beneficial
      action on glomerular capillary pressure, renal fibrotic process, sympathetic
      nerve activity and aldosterone synthesis. It requires more extensive studies to
      clarify whether the ostensibly beneficial actions of these calcium channel
      blockers are available in a clinical setting. 

PMID- 24749518
TI  - Advances in asthma drug discovery: evaluating the potential of nasal cell
      sampling and beyond.
AB  - INTRODUCTION: Inhaled corticosteroid anti-inflammatory therapy is effective at
      controlling disease symptoms of asthma, but a subset of patients remains
      symptomatic despite optimal treatment, creating a clear unmet medical need.
      Moreover, none of the currently available drugs for asthma are really disease
      modifying or curative. Although murine models of asthma, based on transgenic and
      knockout animals, may offer an integrated pathophysiological system for studying
      the characteristics of airway inflammation and hyperresponsiveness, these
      alterations are noteworthily different compared with those observed in asthmatic
      patients. Since a clear functional and inflammatory relationship between the
      nasal mucosa and bronchial tissue in patients suffering from asthma and allergic
      rhinitis has been recognized, using preclinical models based on human nasal cells
      sampling might support a prompt and effective anti-inflammatory drug discovery in
      asthma. AREAS COVERED: The authors provide a review, which discusses the
      potential role of nasal cell sampling and its application in advanced drug
      discovery for asthma. The contents range from the similarities and differences
      between asthma and allergic rhinitis up to artificial airway models based on
      sophisticated human lung-on-a-chip devices. EXPERT OPINION: Nasal cell sampling
      and processing have reached a great potential in asthma drug discovery. The
      authors believe that models of asthma, which are based on human nasal cells, can
      provide valuable indications of proof of pharmacological and potential
      therapeutic efficacy in both preclinical and early clinical settings.

PMID- 24749519
TI  - Ferromagnetic coupling in copper(II) [2 * 2] grid-like complexes.
AB  - Two copper(II) [2 * 2] grid-like complexes were synthesized and structurally
      characterized. Investigation of the magnetic properties showed for both the
      occurrence of intramolecular ferromagnetic interactions. 

PMID- 24749521
TI  - Distinct age-related differences in temporal discounting and risk taking in
      adolescents and young adults.
AB  - Age-related differences in temporal discounting (TD) and risk taking, and their
      association, were examined in adolescents and young adults (n = 337) aged 12-27
      years. Since monetary rewards are typically used in TD and risk-taking tasks, the
      association between monetary reward valuation and age and decision making in
      these tasks was explored as well. TD declined linearly with age, with a
      particularly sharp decline from 15 to 16 years. In contrast, risk taking was not
      correlated with age and TD. Reward valuation was not associated with TD and risk
      taking, and age-related differences in TD remained significant after controlling
      for reward valuation. Together, these findings suggest that risk taking and TD
      are two separate constructs with distinct age-related differences in adolescence
      and young adulthood.

PMID- 24749520
TI  - Long-term impact of the ketogenic diet on growth and resting energy expenditure
      in children with intractable epilepsy.
AB  - AIM: The long-term effects of the ketogenic diet, a high fat diet for treating
      intractable epilepsy, on resting energy expenditure (REE) are unknown. The aim of
      this study was to evaluate the impact of 15 months of ketogenic diet treatment on
      growth and REE in children with intractable epilepsy. METHOD: Growth, body
      composition, and REE were assessed at baseline, 3 months and 15 months in 24
      children (14 males, 10 females; mean age 5 y 6 mo [SD 26 mo], range 7 mo-6 y 5
      mo), 10 with cerebral palsy [CP]). Fifteen were identified as ketogenic diet
      responders at 3 months and continued on the ketogenic diet until 15 months. These
      were compared to 75 healthy children (43 males, 32 females; mean age 6 y 3 mo [SD
      21 mo] age range 2-9 y). REE was expressed as percentage predicted, growth as
      height (HAz) and weight (WAz) z-scores, and body composition as fat and fat free
      mass (FFM). RESULTS: HAz declined -0.2 and -0.6 from baseline to 3 months and 15
      months respectively (p = 0.001), while WAz was unchanged. In ketogenic diet
      responders, FFM, age and CP diagnosis predicted REE (overall R(2) = 0.76,
      p<0.001) and REE did not change. REE adjusted for FFM was lower (p<0.01) in
      children with CP at baseline (mean [standard error], -143[51] kcals/d) and 15
      months (-198[53] kcals/d) compared to the healthy children. INTERPRETATION: After
      15 months of the ketogenic diet, linear growth status declined while weight
      status and REE were unchanged. REE remained reduced in children with CP.

PMID- 24749522
TI  - Durations of bone consolidation and external fixation after distraction
      osteogenesis in dogs.
AB  - OBJECTIVE: To evaluate the influence of epidemiologic, surgical, and mechanical
      factors on the durations of bone consolidation and external fixation after
      distraction osteogenesis in dogs. STUDY DESIGN: Retrospective cohort study.
      SAMPLE POPULATION: Dogs (n = 115) that had corrective osteotomy with circular
      external fixation (CEF; n = 152) METHODS: Medical and radiographic records (1992
      2012) of dogs that had corrective osteotomies were reviewed. Putative variables
      included age, weight, gender, and breed. Surgery date, delay before distraction,
      rate and duration of distraction, mechanical complications, and frame removal
      date were recorded. Radiographic data included bone operated, bone length,
      osteotomy site, bone and limb size at osteotomy site, distraction distance, and
      CEF frame size and stiffness. RESULTS: Mean +/- SD bone consolidation period was
      56 +/- 33 days. Mean duration of external fixation was 77 +/- 35 days. Twelve
      fixation failures occurred. Radii healed faster than tibiae (P < .001). Failure
      of fixation (P = .002) and stiff frames (P = .033) increased duration of bone
      consolidation. For the tibia, durations of bone consolidation and external
      fixation decreased with larger bone size relative to limb size (P = .004). For
      the radius, bone consolidation duration decreased as distraction amount increased
      (P = .03). CONCLUSION: Radii healed faster than tibiae. Wearing frames with low
      or moderate stiffness, the absence of mechanical complications, a larger
      distraction distance, and a larger bone size accelerated bone consolidation.
      Optimizing these factors should accelerate bone consolidation and reduce the
      duration of external fixation.

PMID- 24749523
TI  - Family dynamics and self-injury behaviors: a correlation analysis.
AB  - This study tested the relationship between family dynamics and self-injury. A
      total of 189 participants responded to a web-based survey collecting information
      related to previous self-injury behaviors and family dynamics. Participants were
      over 18 years old who had used self-injury (intentionally harming themselves
      physically to relieve painful emotions without suicidal intent), but who had not
      used self-injury for over a year. Results indicated that healthy family dynamics
      were negatively correlated and associated with higher scores of self-injury
      behaviors. This study offers some evidence that family dynamics influence self
      injury behaviors. The implications for family therapy are discussed. 

PMID- 24749524
TI  - Reducing nitrous oxide emissions to mitigate climate change and protect the ozone
      layer.
AB  - Reducing nitrous oxide (N2O) emissions offers the combined benefits of mitigating
      climate change and protecting the ozone layer. This study estimates historical
      and future N2O emissions and explores the mitigation potential for China's
      chemical industry. The results show that (1) from 1990 to 2012, industrial N2O
      emissions in China grew by some 37-fold from 5.07 to 174 Gg (N2O), with total
      accumulated emissions of 1.26 Tg, and (2) from 2012 to 2020, the projected
      emissions are expected to continue growing rapidly from 174 to 561 Gg under
      current policies and assuming no additional mitigation measures. The total
      accumulated mitigation potential for this forecast period is about 1.54 Tg, the
      equivalent of reducing all the 2011 greenhouse gases from Australia or halocarbon
      ozone-depleting substances from China. Adipic acid production, the major
      industrial emission source, contributes nearly 80% of the industrial N2O
      emissions, and represents about 96.2% of the industrial mitigation potential.
      However, the mitigation will not happen without implementing effective policies
      and regulatory programs. 

PMID- 24749525
TI  - Semiparametric transformation models for semicompeting survival data.
AB  - Semicompeting risk outcome data (e.g., time to disease progression and time to
      death) are commonly collected in clinical trials. However, analysis of these data
      is often hampered by a scarcity of available statistical tools. As such, we
      propose a novel semiparametric transformation model that improves the existing
      models in the following two ways. First, it estimates regression coefficients and
      association parameters simultaneously. Second, the measure of surrogacy, for
      example, the proportion of the treatment effect that is mediated by the surrogate
      and the ratio of the overall treatment effect on the true endpoint over that on
      the surrogate endpoint, can be directly obtained. We propose an estimation
      procedure for inference and show that the proposed estimator is consistent and
      asymptotically normal. Extensive simulations demonstrate the valid usage of our
      method. We apply the method to a multiple myeloma trial to study the impact of
      several biomarkers on patients' semicompeting outcomes--namely, time to
      progression and time to death.

PMID- 24749526
TI  - Correspondence to: soliciting strategies for developing cell-based reference
      materials to advance mesenchymal stem/stromal cell research and clinical
      translation.

PMID- 24749527
TI  - Letter from Italian Psychoanalytical Association.

PMID- 24749528
TI  - 'Ruptures', 27th Conference of the European Psychoanalytic Federation Turin,
      Italy: 10-13 April 2014.

PMID- 24749529
TI  - On: response to Danielle Quinodoz.

PMID- 24749530
TI  - On: Reply to Joseph Schachter's comments.

PMID- 24749531
TI  - On: Covington C (2013). Thinking about climate change: a review essay on Engaging
      with climate change: psychoanalytic and interdisciplinary perspectives.

PMID- 24749533
TI  - Current status of antifungal resistance and its impact on clinical practice.
AB  - Mortality linked to invasive fungal diseases remains very high despite the
      availability of novel antifungals and new therapeutic strategies. Candida
      albicans and Aspergillus fumigatus account for most invasive mycosis produced by
      yeast or moulds, respectively. Other Candida non-albicans are increasingly being
      reported and newly emerging, as well as cryptic, filamentous fungi often cause
      disseminated infections in immunocompromised hosts. Management of invasive fungal
      infections is becoming a challenge as emerging fungal pathogens generally show
      poor response to many antifungals. The ability of reference antifungal
      susceptibility testing methods to detect emerging resistance patterns, together
      with the molecular characterization of antifungal resistance mechanisms, are
      providing useful information to optimize the effectiveness of antifungal therapy.
      The current status of antifungal resistance epidemiology with special emphasis on
      the molecular resistant mechanisms that have been described in the main
      pathogenic fungal species are reviewed. 

PMID- 24749534
TI  - Understanding the mechanical properties of DNA origami tiles and controlling the
      kinetics of their folding and unfolding reconfiguration.
AB  - DNA origami represents a class of highly programmable macromolecules that can go
      through conformational changes in response to external signals. Here we show that
      a two-dimensional origami rectangle can be effectively folded into a short,
      cylindrical tube by connecting the two opposite edges through the hybridization
      of linker strands and that this process can be efficiently reversed via toehold
      mediated strand displacement. The reconfiguration kinetics was experimentally
      studied as a function of incubation temperature, initial origami concentration,
      missing staples, and origami geometry. A kinetic model was developed by
      introducing the j factor to describe the reaction rates in the cyclization
      process. We found that the cyclization efficiency (j factor) increases sharply
      with temperature and depends strongly on the structural flexibility and geometry.
      A simple mechanical model was used to correlate the observed cyclization
      efficiency with origami structure details. The mechanical analysis suggests two
      sources of the energy barrier for DNA origami folding: overcoming global twisting
      and bending the structure into a circular conformation. It also provides the
      first semiquantitative estimation of the rigidity of DNA interhelix crossovers,
      an essential element in structural DNA nanotechnology. This work demonstrates
      efficient DNA origami reconfiguration, advances our understanding of the dynamics
      and mechanical properties of self-assembled DNA structures, and should be
      valuable to the field of DNA nanotechnology. 

PMID- 24749535
TI  - Unique DC-SIGN clustering activity of a small glycomimetic: A lesson for ligand
      design.
AB  - DC-SIGN is a dendritic cell-specific C-type lectin receptor that recognizes
      highly glycosylated ligands expressed on the surface of various pathogens. This
      receptor plays an important role in the early stages of many viral infections,
      including HIV, which makes it an interesting therapeutic target. Glycomimetic
      compounds are good drug candidates for DC-SIGN inhibition due to their high
      solubility, resistance to glycosidases, and nontoxicity. We studied the
      structural properties of the interaction of the tetrameric DC-SIGN extracellular
      domain (ECD), with two glycomimetic antagonists, a pseudomannobioside (1) and a
      linear pseudomannotrioside (2). Though the inhibitory potency of 2, as measured
      by SPR competition experiments, was 1 order of magnitude higher than that of 1,
      crystal structures of the complexes within the DC-SIGN carbohydrate recognition
      domain showed the same binding mode for both compounds. Moreover, when conjugated
      to multivalent scaffolds, the inhibitory potencies of these compounds became
      uniform. Combining isothermal titration microcalorimetry, analytical
      ultracentrifugation, and dynamic light scattering techniques to study DC-SIGN ECD
      interaction with these glycomimetics revealed that 2 is able, without any
      multivalent presentation, to cluster DC-SIGN tetramers leading to an artificially
      overestimated inhibitory potency. The use of multivalent scaffolds presenting 1
      or 2 in HIV trans-infection inhibition assay confirms the loss of potency of 2
      upon conjugation and the equal efficacy of chemically simpler compound 1. This
      study documents a unique case where, among two active compounds chemically
      derived, the compound with the lower apparent activity is the optimal lead for
      further drug development.

PMID- 24749536
TI  - Optimising the effects of rigid ankle foot orthoses on the gait of children with
      cerebral palsy (CP) - an exploratory trial.
AB  - Abstract Purpose: This exploratory trial investigated the effects of rigid ankle
      foot orthoses (AFO) with an optimally cast Angle of the Ankle in the AFO (AAAFO)
      on the gait of children with Cerebral Palsy (CP), and whether tuning of the AFO -
      Footwear Combination (AFO-FC) further affected gait. Methods: Eight children with
      CP underwent gait analysis and tuning of their AFO-FCs using a 3-D motion
      analysis system. Comparisons were carried out for selected gait parameters
      between three conditions - barefoot, non-tuned AFO-FC and tuned AFO-FC. Results:
      In comparison to barefoot gait, walking with a non-tuned AFO-FC produced
      significant (p < 0.05) improvements in several key gait parameters. Compared to
      the non-tuned AFO-FC, on average a tuned AFO-FC produced a significant reduction
      in peak knee extension and knee ROM during gait. However, when examined as case
      studies, it was observed that the type of gait pattern demonstrated while wearing
      a non-tuned AFO-FC affected the outcomes of tuning. Conclusions: The findings of
      the current study indicate the potential benefits of using rigid AFO-FC with
      optimal AAAFO and tuning of AFO-FCs. This study emphasises the need for
      categorising children with CP based on their gait patterns when investigating the
      effects of interventions such as AFOs. Implications for Rehabilitation Rigid
      ankle foot orthoses (AFO) cast at an optimal angle to accommodate the length of
      gastrocnemius muscle may positively influence walking in children with Cerebral
      Palsy (CP). Tuning of the AFO-Footwear Combination (AFO-FC) has potential
      benefits to the walking of children with CP, depending on their gait
      abnormalities. When investigating the effects of interventions such as AFOs, it
      is important to categorise children with CP based on their gait abnormalities.

PMID- 24749537
TI  - Isoflavanones from Desmodium oxyphyllum and their cytotoxicity.
AB  - Two new isoflavanones, (3R)-7-hydroxy-4'-methoxy-5-methoxycarbonyl-isoflavanone
      (1) and (3R)-8-hydroxy-4'-methoxy-7-methoxycarbonyl-isoflavanone (2), together
      with seven known isoflavanones (3-9) were isolated from Desmodium oxyphyllum of
      the Leguminosae family. Their structures were elucidated by spectroscopic
      methods, including extensive 1D and 2D NMR techniques. Compound 1 showed good
      cytotoxicity against NB4 and SHSY5Y cell lines with IC50 values of 3.1 and 2.5
      MUM; compound 2 exhibited cytotoxicity against PC3 cell lines with a IC50 value
      of 3.6 MUM; compound 4 showed cytotoxicity against A549 and SHSY5Y cell lines
      with IC50 values of 3.6 and 2.8 MUM; and compound 5 displayed cytotoxicity
      against NB4, SHSY5Y, and MCF7 cell lines with IC50 values of 2.6, 3.8, and 2.8
      MUM, respectively. Other compounds also showed moderate cytotoxicity for some
      tested cell lines with IC50 values between 5.4 and 8.8 MUM.

PMID- 24749538
TI  - Novel techniques in the development of osteoporosis drug therapy: the osteoclast
      ruffled-border vacuolar H(+)-ATPase as an emerging target.
AB  - INTRODUCTION: Bone loss occurs in many diseases, including osteoporosis,
      rheumatoid arthritis and periodontal disease. For osteoporosis alone, it is
      estimated that 75 million people are afflicted worldwide, with high risks of
      fractures and increased morbidity and mortality. The demand for treatment
      consumes an ever-increasing share of healthcare resources. Successive generations
      of antiresorptive bisphosphonate drugs have reduced side effects, minimized
      frequency of dosing, and increased efficacy in halting osteoporotic bone loss,
      but their shortcomings have remained significant to the extent that a monoclonal
      antibody antiresorptive has recently taken a significant market share. Yet this
      latter, paradigm-shifting approach has its own drawbacks. AREAS COVERED: This
      review summarizes recent literature on bone-remodeling cell and molecular biology
      and the background for existing approaches and emerging therapeutics and targets
      for treating osteoporosis. The authors discuss vacuolar H(+)-ATPase (V-ATPase)
      molecular biology and the recent advances in targeting the osteoclast ruffled
      border V-ATPase (ORV) for the development of novel antiresorptive drugs. They
      also cover examples from the V-ATPase-targeted drug discovery literature,
      including conventional molecular biology methods, in silico drug discovery, and
      gene therapy in more detail as proofs of concept. EXPERT OPINION: Existing
      therapeutic options for osteoporosis have limitations and inherent drawbacks.
      Thus, the search for novel approaches to osteoporosis drug discovery remains
      relevant. Targeting the ORV may be one of the more selective means of regulating
      bone resorption. Furthermore, this approach may be effective without removing
      active osteoclasts from the finely balanced osteoclast-osteoblast coupling
      required for normal bone remodeling.

PMID- 24749540
TI  - The sea anemone toxin AdE-1 modifies both sodium and potassium currents of rat
      cardiomyocytes.
AB  - AdE-1, a cardiotonic peptide recently isolated from the sea anemone Aiptasia
      diaphana, contains 44 amino acids and has a molecular mass of 4907 Da. It was
      previously found to resemble other sea anemone type 1 and 2 Na+ channel toxins,
      enhancing contractions of rat cardiomyocytes and slowing their twitch relaxation;
      however, it did not induce spontaneous twitches. AdE-1 increased the duration of
      the cardiomyocyte action potential and decreased its amplitude and its time-to
      peak in a concentration-dependent manner, without affecting its threshold and
      cell resting potential. Nor did it generate the early and delayed after
      depolarizations characteristic of sea anemone Na+ channel toxins. To further
      understand its mechanism of action we investigated the effect of AdE-1 on the
      major ion currents of rat cardiomyocytes. In the present study we show that AdE-1
      markedly slowed inactivation of the Na+ current, enhancing and prolonging the
      current influx with no effect on current activation, possibly through direct
      interaction with the site 3 receptor of the Na+ channel. No significant effect of
      AdE-1 on the Ca2+ current was observed, but, unexpectedly, AdE-1 significantly
      increased the amplitude of the transient component of the K+ current, shifting
      the current threshold to more negative membrane potentials. This effect on the K+
      current has not been found in any other sea anemone toxin and may explain the
      exclusive reduction in action potential amplitude and the absence of the action
      potential disorders found with other toxins, such as early and delayed after
      depolarizations. 

PMID- 24749541
TI  - Traumatic brain injury-induced ependymal ciliary loss decreases cerebral spinal
      fluid flow.
AB  - Traumatic brain injury (TBI) afflicts up to 2 million people annually in the
      United States and is the primary cause of death and disability in young adults
      and children. Previous TBI studies have focused predominantly on the
      morphological, biochemical, and functional alterations of gray matter structures,
      such as the hippocampus. However, little attention has been given to the brain
      ventricular system, despite the fact that altered ventricular function is known
      to occur in brain pathologies. In the present study, we investigated anatomical
      and functional alterations to mouse ventricular cilia that result from mild TBI.
      We demonstrate that TBI causes a dramatic decrease in cilia. Further, using a
      particle tracking technique, we demonstrate that cerebrospinal fluid flow is
      diminished, thus potentially negatively affecting waste and nutrient exchange.
      Interestingly, injury-induced ventricular system pathology resolves completely by
      30 days after injury as ependymal cell ciliogenesis restores cilia density to
      uninjured levels in the affected lateral ventricle.

PMID- 24749542
TI  - General strategy for the bioorthogonal incorporation of strongly absorbing,
      solvation-sensitive infrared probes into proteins.
AB  - A high-sensitivity metal-carbonyl-based IR probe is described that can be
      incorporated into proteins or other biomolecules in very high yield via Click
      chemistry. A two-step strategy is demonstrated. First, a methionine auxotroph is
      used to incorporate the unnatural amino acid azidohomoalanine at high levels.
      Second, a tricarbonyl (eta(5)-cyclopentadienyl) rhenium(I) probe modified with an
      alkynyl linkage is coupled via the Click reaction. We demonstrate these steps
      using the C-terminal domain of the ribosomal protein L9 as a model system. An
      overall incorporation level of 92% was obtained at residue 109, which is a
      surface-exposed residue. Incorporation of the probe into a surface site is shown
      not to perturb the stability or structure of the target protein. Metal carbonyls
      are known to be sensitive to solvation and protein electrostatics through
      vibrational lifetimes and frequency shifts. We report that the frequencies and
      lifetimes of this probe also depend on the isotopic composition of the solvent.
      Comparison of the lifetimes measured in H2O versus D2O provides a probe of
      solvent accessibility. The metal carbonyl probe reported here provides an easy
      and robust method to label very large proteins with an amino-acid-specific tag
      that is both environmentally sensitive and a very strong absorber. 

PMID- 24749543
TI  - Inhibition of proteasome-mediated glucocorticoid receptor degradation restores
      nitric oxide bioavailability in myocardial endothelial cells in vitro.
AB  - BACKGROUND INFORMATION: Glucocorticoids (GCs), including the synthetic GC
      derivate dexamethasone, are widely used as immunomodulators. One of the numerous
      side effects of dexamethasone therapy is hypertension arising from reduced
      release of the endothelium-derived vasodilator nitric oxide (NO). RESULTS:
      Herein, we described the role of dexamethasone and its glucocorticoid receptor
      (GR) in the regulation of NO synthesis in vitro using the mouse myocardial
      microvascular endothelial cell line, MyEND. GC treatment caused a firm decrease
      of extracellular NO levels, whereas the expression of endothelial NO synthase
      (eNOS) was not affected. However, GC application induced an impairment of
      tetrahydrobiopterin (BH4 ) concentrations as well as GTP cyclohydrolase-1 (GTPCH
      1) expression, both essential factors for NO production upstream of eNOS.
      Moreover, dexamethasone stimulation resulted in a substantially decreased GR gene
      and protein expression in MyEND cells. Importantly, inhibition of proteasome
      mediated proteolysis of the GR or overexpression of an ubiquitination-defective
      GR construct improved the bioavailability of BH4 and strengthened GTPCH-1
      expression and eNOS activity. CONCLUSIONS: Summarising our results, we propose a
      new mechanism involved in the regulation of NO signalling by GCs in myocardial
      endothelial cells. We suggest that a sufficient GR protein expression plays a
      crucial role for the management of GC-induced harmful adverse effects, including
      deregulations of vasorelaxation arising from disturbed NO biosynthesis.

PMID- 24749544
TI  - Scaffolding along nucleic acid duplexes using 2'-amino-locked nucleic acids.
AB  - CONSPECTUS: Incorporation of chemically modified nucleotide scaffolds into
      nucleic acids to form assemblies rich in function is an innovative area with
      great promise for nanotechnology and biomedical and material science
      applications. The intrinsic biorecognition potential of nucleic acids combined
      with advanced properties of the locked nucleic acids (LNAs) provide opportunities
      to develop new nanomaterials and devices like sensors, aptamers, and machines. In
      this Account, we describe recent research on preparation and investigation of the
      properties of LNA/DNA hybrids containing functionalized 2'-amino-LNA nucleotides.
      By application of different chemical reactions, modification of 2'-amino-LNA
      scaffolds can be efficiently performed in high yields and with various tags,
      postsynthetically or during the automated oligonucleotide synthesis. The choice
      of a synthetic method for scaffolding along 2'-amino-LNA mainly depends on the
      chemical nature of the modification, its price, its availability, and
      applications of the product. One of the most useful applications of the product
      LNA/DNA scaffolds containing 2'-amino-LNA is to detect complementary DNA and RNA
      targets. Examples of these applications include sensing of clinically important
      single-nucleotide polymorphisms (SNPs) and imaging of nucleic acids in vitro, in
      cell culture, and in vivo. According to our studies, 2'-amino-LNA scaffolds are
      efficient within diagnostic probes for DNA and RNA targets and as therapeutics,
      whereas both 2'-amino- and isomeric 2'-alpha-l-amino-LNA scaffolds have promising
      properties for stabilization and detection of DNA nanostructures. Attachment of
      fluorescent groups to the 2'-amino group results in very high fluorescent quantum
      yields of the duplexes and remarkable sensitivity of the fluorescence signal to
      target binding. Notably, fluorescent LNA/DNA probes bind nucleic acid targets
      with advantages of high affinity and specificity. Thus, molecular motion of
      nanodevices and programmable self-assembly of chemically modified LNA/DNA
      nanomaterials can be followed by bright fluorescence signaling from the
      functionalized LNA units. Another appealing aspect of the amino-LNA scaffolds is
      specific targeting of nucleic acids and proteins for therapeutic applications. 2'
      Amino-LNA/DNA conjugates containing peptide and polyaromatic hydrocarbon (PAH)
      groups are promising in this context as well as for advanced imaging and
      diagnostic purposes in vivo. For imaging applications, photostability of
      fluorescence dyes is of crucial importance. Chemically stable and photostable
      fluorescent PAH molecules attached to 2'-amino functionality of the 2'-amino-LNA
      are potent for in vitro and in vivo imaging of DNA and RNA targets. We believe
      that rational evolution of the biopolymers of Nature may solve the major
      challenges of the future material science and biomedicine. However, this requires
      strong scientific progress and efficient interdisciplinary research. Examples of
      this Account demonstrate that among other synthetic biopolymers, synthetic
      nucleic acids containing functionalized 2'-amino-LNA scaffolds offer great
      opportunities for material science, diagnostics, and medicine of the future.

PMID- 24749545
TI  - Parasites and genetic diversity in an invasive bumblebee.
AB  - Biological invasions are facilitated by the global transportation of species and
      climate change. Given that invasions may cause ecological and economic damage and
      pose a major threat to biodiversity, understanding the mechanisms behind invasion
      success is essential. Both the release of non-native populations from natural
      enemies, such as parasites, and the genetic diversity of these populations may
      play key roles in their invasion success. We investigated the roles of parasite
      communities, through enemy release and parasite acquisition, and genetic
      diversity in the invasion success of the non-native bumblebee, Bombus hypnorum,
      in the United Kingdom. The invasive B. hypnorum had higher parasite prevalence
      than most, or all native congeners for two high-impact parasites, probably due to
      higher susceptibility and parasite acquisition. Consequently parasites had a
      higher impact on B. hypnorum queens' survival and colony-founding success than on
      native species. Bombus hypnorum also had lower functional genetic diversity at
      the sex-determining locus than native species. Higher parasite prevalence and
      lower genetic diversity have not prevented the rapid invasion of the United
      Kingdom by B. hypnorum. These data may inform our understanding of similar
      invasions by commercial bumblebees around the world. This study suggests that
      concerns about parasite impacts on the small founding populations common to re
      introduction and translocation programs may be less important than currently
      believed. 

PMID- 24749546
TI  - Robust, quantitative analysis of proteins using peptide immunoreagents, in vitro
      translation, and an ultrasensitive acoustic resonant sensor.
AB  - A major benefit of proteomic and genomic data is the potential for developing
      thousands of novel diagnostic and analytical tests of cells, tissues, and
      clinical samples. Monoclonal antibody technologies, phage display and mRNA
      display, are methods that could be used to generate affinity ligands against each
      member of the proteome. Increasingly, the challenge is not ligand generation,
      rather the analysis and affinity rank-ordering of the many ligands generated by
      these methods. Here, we developed a quantitative method to analyze protein
      interactions using in vitro translated ligands. In this assay, in vitro
      translated ligands generate a signal by simultaneously binding to a target
      immobilized on a magnetic bead and to a sensor surface in a commercial acoustic
      sensing device. We then normalize the binding of each ligand with its relative
      translation efficiency in order to rank-order the different ligands. We
      demonstrate the method with peptides directed against the cancer marker Bcl-xL.
      Our method has 4- to 10-fold higher sensitivity, using 100-fold less protein and
      5-fold less antibody per sample, as compared directly with ELISA. Additionally,
      all analysis can be conducted in complex mixtures at physiological ionic
      strength. Lastly, we demonstrate the ability to use peptides as ultrahigh
      affinity reagents that function in complex matrices, as would be needed in
      diagnostic applications. 

PMID- 24749547
TI  - Factors influencing self-reported use of antioxidant supplements in patients with
      age-related macular degeneration.
AB  - AIM: The goals of the present study were to evaluate the current use and accuracy
      of dose-taking prescription among patients with age-related macular degeneration
      (AMD) and to detect potential factors influencing the use or non-use of oral
      antioxidant supplements. MATERIALS AND METHODS: This is a cross-sectional
      questionnaire-based study of 65 patients with AMD of Age-Related Eye Disease
      Study (AREDS) category 3 (intermediate AMD) or category 4 (unilateral advanced
      AMD). Self-report data were obtained from a structural clinical interview in
      clinic. The patients were asked questions regarding their demographic,
      ophthalmologic and systemic data, their source of recommendation for antioxidant
      supplement use and/or their reasons for non-use. Afterwards, this information was
      correlated with the use or non-use of antioxidant supplements. Statistical
      analyses were conducted using a series of Mann-Whitney U-tests and Fisher's exact
      tests. RESULTS: There were 55.4% (36 of 65) of the patients reporting antioxidant
      supplement use for AMD and 44.6% (29 of 65) with no supplement use. However, only
      56.7% (17 of 30) took the recommended dose on label. There were significantly
      more female patients taking supplements than male patients (p = 0.010). A
      statistically significant correlation was also found between supplement use and
      the number of visits to an ophthalmologist per year (p = 0.037). The main reason
      for antioxidant supplement non-use was the missing awareness of the availability
      of antioxidant supplements. CONCLUSIONS: Despite the recommendation of oral
      antioxidant supplements in the ARED Study for patients with AMD of category 3 or
      4, only about half of these patients took the supplements in this study.
      Identifying the factors, which influenced the decision against supplement use,
      may help to better support patients in the prevention of severe vision loss
      caused by AMD.

PMID- 24749548
TI  - Chemical reduction of individual graphene oxide sheets as revealed by
      electrostatic force microscopy.
AB  - We report continuous monitoring of heterogeneously distributed oxygenated
      functionalities on the entire surface of the individual graphene oxide flake
      during the chemical reduction process. The charge densities over the surface with
      mixed oxidized and graphitic domains were observed for the same flake after a
      step-by-step chemical reduction process using electrostatic force microscopy.
      Quantitative analysis revealed heavily oxidized nanoscale domains (50-100 nm
      across) on the graphene oxide surface and a complex reduction mechanism involving
      leaching of sharp oxidized asperities from the surface followed by gradual
      thinning and formation of uniformly mixed oxidized and graphitic domains across
      the entire flake. 

PMID- 24749549
TI  - Growth of social competence during the preschool years: a 3-year longitudinal
      study.
AB  - This study examined the stability and growth over a 3-year period of individual
      differences in preschool children's social competence, which was assessed in
      three domains: social engagement/motivation, profiles of behavior and personality
      attributes characteristic of socially competent young children, and peer
      acceptance. A total of 255 children (126 girls and 129 boys) participated in this
      study. Growth curve analyses demonstrated both stability and change with regard
      to social competence over early childhood. Social competence measures and latent
      variables were invariant over this time period, individual differences in social
      competence were largely stable from year to year, and significant increases over
      time were observed for the domain most closely reflective of specific personal
      attributes skills. 

PMID- 24749550
TI  - Longitudinal associations between executive functioning and academic skills
      across content areas.
AB  - This study assessed 562 four-year-old children at the beginning and end of their
      prekindergarten (pre-k) year and followed them to the end of kindergarten. At
      each time point children were assessed on 6 measures of executive function (EF)
      and 5 subtests of the Woodcock-Johnson III academic achievement battery.
      Exploratory factor analyses yielded EF and achievement factor scores. We examined
      the longitudinal bidirectional associations between these domains as well as the
      bidirectional associations among the separate content areas and the EF factor. In
      the pre-k year, strong bidirectional associations were found for EF skills and
      mathematics and oral comprehension skills but not for literacy skills. After
      controlling for pre-k gains in both EF and achievement, EF skills continued to be
      strong predictors of gains in mathematics in kindergarten and a more moderate
      predictor of kindergarten language gains. These results provide important
      information on the interrelationship of the developmental domains of EF and
      achievement as well as support for efforts to determine effective pre-k
      activities and/or curricula that can improve children's EF skills. They also
      suggest that mathematics activities may be a possible avenue for improving EF
      skills in young children.

PMID- 24749551
TI  - Extracurricular participation and the development of school attachment and
      learning goal orientation: the impact of school quality.
AB  - School motivation and attachment typically decline after the transition to middle
      school. According to the stage-environment fit approach, extracurricular
      activities are supposed to promote motivation. However, research has shown that
      the effects depend on the quality of the activities, which usually is measured by
      assessing students' individual perceptions. This article adds to previous studies
      in examining effects of school-based extracurricular participation on the
      development of individual motivation (learning goal orientation) and school
      attachment depending on the quality of the activities (i.e., amounts of challenge
      and social support) at the school level. We focused on the motivation development
      of 3,230 students at 98 schools who filled in questionnaires in Grades 5 (2005),
      7 (2007), and 9 (2009). The quality of extracurricular activities was assessed on
      the basis of responses from 4,270 students in Grades 5, 7, and 9 at the same
      schools at the first measurement point (2005). Thus, individual development of
      the longitudinal sample was predicted by aggregated quality measures at the
      school level. Three-level hierarchical linear growth-curve models including
      school level, student level, and time were calculated. Cross-level interactions
      were analyzed to examine the influence of extracurricular participation on
      individual development as a function of school quality. Results show that the
      effects of extracurricular participation on the development of learning goal
      orientation are dependent on both features of school quality, whereas the
      development of school attachment in particular is influenced by activities
      offering social support. Thus, the effects of extracurricular activities are
      based not only on individual perceptions of activity features but also on school
      quality.

PMID- 24749552
TI  - The development of relational integration during childhood.
AB  - Relational integration refers to the process whereby several variables are
      integrated within a single cognitive representation. In cognitive and
      developmental science, it is regarded as a central function of working memory
      that may contribute to the development of higher order processes, such as
      reasoning and fluid intelligence. In the present experiment, we administered the
      Relational Integration Level Assessment Task (RILAT), a novel experimental task
      designed to assess children's level of relational integration, to participants
      aged 5-12 years, along with a measure of fluid intelligence. Results yielded age
      norms for the development of successive levels of relational complexity and
      indicated a smooth progression rather than abrupt, stage-like transitions.
      Relational integration was found to be closely associated with fluid
      intelligence, as measured by Raven's Progressive Matrices. Analyses of age
      related changes in this association revealed that the relationship was strongest
      during the stabilization periods for each level of relational complexity.

PMID- 24749553
TI  - Does Ramadan fasting affect the intensity of acenocoumarol-induced anticoagulant
      effect?

PMID- 24749554
TI  - Haptic perception of users with low vision and their needs in haptic-incorporated
      user interfaces.
AB  - PURPOSE: This paper reports on research aimed at advancing understanding haptic
      capability and needs of users with low vision. The objective is to apply this
      understanding to the design of haptic-incorporated user interfaces. METHOD: Study
      1 investigated the haptic perception between sighted participants and those with
      low vision through the magnitude estimation technique, and Study 2 explored the
      degree to which similar user interface needs were observed among the two vision
      groups. RESULTS: Overall, our findings indicate there was no significant
      difference between the two vision groups in terms of haptic perception and user
      interface needs. A few differences in user interface preference did exist,
      however, and designers should take these into account. CONCLUSIONS: Participants
      with low vision were a group who relied on their vision in everyday life instead
      of touch. Thus, their haptic capability was less likely to be enhanced via brain
      plasticity, which probably contributed to no significant difference in haptic
      incorporated user interface needs. IMPLICATIONS FOR REHABILITATION: No
      significant different haptic capability and haptic user interface (UI) needs
      exists between cited participants and those with low vision. UI designers should
      take into consideration that a certain range of magnitude/type of haptic feedback
      is available to accommodate preferences of both vision groups, which would
      ultimately increase the likelihood of successfully developing universal designs.

PMID- 24749555
TI  - Validating the wheelchair outcome measure for residents in long-term care.
AB  - PURPOSE: To determine the retest reliability and construct validity of the self
      report and proxy versions of the wheelchair outcome measure (WhOM) among
      residents in long-term care. METHOD: The WhOM was administered to 55 wheelchair
      users living in residential care (38 self-respondents and 17 proxy respondents).
      Retest data were collected to estimate reliability using intraclass correlation
      coefficients (ICCs) for each of the tool scores (Importance, Satisfaction and
      Importance * Satisfaction). For construct validity testing, Spearman's
      correlation coefficients were used to assess whether WhOM scores were correlated
      with scores from the Late Life Function and Disability Instrument (LLDI) and
      Geriatric Depression Scale (GDS). RESULTS: The ICCs for the WhOM scores were
      between 0.68 and 0.84. Moderate correlations were found between the self
      respondents and proxy respondents groups with Importance * Satisfaction and LLDI
      (r = 0.46-0.50). No other significant correlations were found. CONCLUSIONS: This
      study provides evidence for the reliability and validity of the WhOM for adults
      in residential care, but further testing is warranted to ensure it can facilitate
      prescription of the right device at the right time for residents in these
      settings. IMPLICATIONS FOR REHABILITATION: Clients who reside in long-term care
      (LTC) institutions represent a population who have unique needs because of the
      varied types of activities in which they participate. This study provides support
      for use of the WhOM on an individual basis among self-responding residents. The
      study provides some support and use of the WhOM with groups of residents who
      require proxy respondents. Additional studies with a larger sample size are
      needed to further explore the psychometrics of the measure.

PMID- 24749556
TI  - Influence of orthotic gait training with powered hip orthosis on walking in
      paraplegic patients.
AB  - OBJECTIVES: Gait training has been shown to improve the walking performance of
      spinal cord-injured (SCI) patients. The use of powered hip orthoses (PHO) during
      gait training is one approach which could potentially improve rehabilitative
      outcomes for such subjects. The aim of this study was therefore to evaluate the
      influence of a PHO on the kinematics and temporal-spatial parameters of walking
      by SCI patients. METHODS: Four SCI patients participated in this study. Gait
      evaluation was performed at baseline and at 10 weeks following intervention with
      the use of a PHO and gait re-training. Walking speed, step length, vertical and
      horizontal compensatory motions and hip joint kinematics were analysed prior to
      and following the training regime. RESULTS: Significant increases in walking
      speed and step length were demonstrated by the SCI patients when walking with the
      PHO following orthotic gait training. Sagittal plane hip range of motion also
      increased, but not significantly. However, vertical and horizontal compensatory
      motions decreased significantly. CONCLUSIONS: Positive effects on the kinematics
      and temporal-spatial parameters of gait by SCI subjects were demonstrated
      following a period of gait training with a PHO. Further studies are therefore
      warranted to confirm their long term effects on the rehabilitation of SCI
      subjects. IMPLICATIONS FOR REHABILITATION: Powered hip orthosis could be used by
      spinal cord injury patients. A major advantage of the orthotic gait training with
      powered hip orthosis was regeneration of hip movement closer to that of normal
      human walking. The orthotic gait training with the powered hip orthosis improved
      the kinematics and temporalspatial parameters in a spinal cord injury patient
      which also produced near-normal hip joint angle patterns during gait.

PMID- 24749557
TI  - Congenital cytomegalovirus is associated with severe forms of cerebral palsy and
      female sex in a retrospective population-based study.
AB  - AIM: Congenital cytomegalovirus (cCMV) infection can result in poor outcomes
      including cerebral palsy (CP). The aim of this study was to describe the
      incidence and comorbidities of CP reported to the Australian Cerebral Palsy
      Register (ACPR) as attributed to cCMV infection. METHOD: This was a retrospective
      population-based study. Cases were drawn from Australian state CP registers with
      population level ascertainment, 1993 to 2003 (n=2265; 56.4% males, Gross Motor
      Function Classification System [GMFCS] ratings available for Victorian cases
      only: 70% GMFCS levels I to III and 30% GMFCS levels IV to V). Clinical data were
      extracted and cases with cCMV reported as a known cause were compared with cases
      where cCMV was not reported. RESULTS: Children with cCMV (n=34; 12 males, 22
      females; mean [SD] gestational age, 36.4 wk [4.4], range 24-41 wk) accounted for
      1.5% of CP cases; 2.9 per 100,000 live births, (95% confidence intervals 1.9
      3.9). When compared with CP cases where cCMV was not reported, proportionally,
      more CP cases with cCMV were born to younger mothers (p<0.001), were female (64%
      vs 43%, p=0.014), had spastic quadriplegia (73% vs 21%, p<0.001), required
      wheeled mobility i.e. GMFCS IV or V (78% vs 28%, p<0.001), had epilepsy (70% vs
      30%, p<0.001), deafness (40% vs 2%, p<0.001), functional blindness (20% vs 5%,
      p<0.001), and severe communication impairment (71% vs 25%, p<0.001).
      INTERPRETATION: cCMV is an important potentially preventable cause of CP and is
      associated with severe disability and female sex in cases reported to the ACPR.
      Future studies utilising prospective sample collection for cCMV testing are
      needed to confirm these findings.

PMID- 24749559
TI  - Selectivity of azine ligands toward lanthanide(III)/actinide(III)
      differentiation: a relativistic DFT based rationalization.
AB  - Polyazines emerge as highly selective ligands toward actinide versus lanthanide
      separation. Electronic structures of several mono- and polyazine f-complexes of
      general formula MX3L (M(+3) = Ce, Nd, Eu, U, Am, and Cm; X = RCp(-) or NO3(-); L
      = N-donor ligand) related to Ln(III)/An(III) differentiation have been
      investigated using scalar relativistic ZORA/DFT calculations. In all cases, DFT
      calculations predict shorter An-N bonds than Ln-N ones whatever the azine used,
      in good agreement with available experimental data. The An-N bonds are also
      characterized by higher stretching frequencies than Ln-N bonds. The electronic
      structures of all species have been studied using different population analyses,
      among them natural population (NPA) and the quantum theory of atoms in molecule
      approach (QTAIM), as well as using different bond indices. The ability for
      Ln(III)/An(III) differentiation of the terdentate bipyrazolate BPPR ligand in the
      M(BPPR)(NO3)3 complexes (M(3+) = Ce, Eu, U and Am ; R = H, 2,2-dimethylpropyl)
      where BPP = 2,6-bis(dialkyl-1H-pyrazol-3-yl)pyridine has been studied, with a
      special emphasis on the total metal-ligand bonding energy (TBE). The ZORA/DFT
      approach was found to properly reproduce the higher selectivity of the polyazine
      BPP ligand compared to monoazines, especially for the Eu(III)/Am(III) pair
      operating in spent nuclear fuel, using computed TBEs as criterion. Moreover, the
      orbital part of the total bonding energy appears also to rationalize well the
      observed selectivity. 

PMID- 24749558
TI  - Inhibition of TROY promotes OPC differentiation and increases therapeutic
      efficacy of OPC graft for spinal cord injury.
AB  - Endogenous or graft-derived oligodendrocytes promote myelination and aid in the
      recovery from central nervous system (CNS) injury. Regulatory mechanisms
      underlying neural myelination and remyelination in response to injury, including
      spinal cord injury (SCI), are unclear. In the present study, we demonstrated that
      TROY serves as an important negative regulator of oligodendrocyte development and
      that TROY inhibition augments the repair potential of oligodendrocyte precursor
      cell (OPC) graft for SCI. TROY expression was detected by reverse transcriptase
      polymerase chain reaction in OPCs as well as in differentiated premature and
      mature oligodendrocytes of postnatal mice. Pharmacological inhibition or RNAi
      induced knockdown of TROY promotes OPC differentiation, whereas overexpression of
      TROY dampens oligodendrocyte maturation. Further, treatment of cocultures of DRG
      neurons and OPCs with TROY inhibitors promotes myelination and myelin-sheath-like
      structures. Mechanically, protein kinase C (PKC) signaling is involved in the
      regulation of the inhibitory effects of TROY. Moreover, in situ transplantation
      of OPCs with TROY knockdown leads to notable remyelination and neurological
      recovery in rats with SCI. Our results indicate that TROY negatively modulates
      remyelination in the CNS, and thus may be a suitable target for improving the
      therapeutic efficacy of cell transplantation for CNS injury. 

PMID- 24749560
TI  - Urethral prolapse in dogs: a retrospective study.
AB  - OBJECTIVE: To evaluate the signalment, clinical signs, treatment, and outcome of
      dogs with urethral prolapse and identify risk factors associated with prolapse or
      treatment. STUDY DESIGN: Retrospective case series. ANIMALS: Dogs (n = 48) with
      urethral prolapse. METHODS: Medical records (May 1995-June 2010) from 2 referral
      centers were reviewed. Retrieved data included signalment, clinical signs,
      laboratory findings, treatment, complications, results of long-term follow-up.
      Records from Veterinary Medical Data Base (VMDB) were evaluated to determine odds
      ratios. RESULTS: Odds ratio for urethral prolapse in English bulldogs compared to
      all breeds was 366.99 (95% CI: 265.83, 506.65). Of 48 affected dogs, 46 had
      either resection and anastomosis (43 dogs) or urethropexy (3 dogs). The most
      common early postoperative complication was hemorrhage (39%); postoperative
      hemorrhage was less common when a simple continuous pattern was used for
      resection and anastomosis. Prolapse recurred in 57% of dogs available for long
      term follow-up; recurrence was less common in dogs that were administered
      postoperative butorphanol or acepromazine. Gender was not associated with
      urethral prolapse or postoperative complications. CONCLUSIONS: Urethral prolapse
      occurs most commonly in English bulldogs. Postoperative hemorrhage and prolapse
      recurrence may be reduced with use of a simple continuous pattern for urethral
      anastomosis and by administration of postoperative sedation, respectively.
      Castration status did not appear to affect prolapse development or outcome.

PMID- 24749561
TI  - Monoterpenes from the fruits of Amomum kravanh.
AB  - Two new monoterpenes, (7S)-p-cymene-2,7,8-triol (1) and (3R,4R,6S)-p-menth-1-ene
      3,6,10-triol (2), were isolated from the fruits of Amomum kravanh. Their
      structures were established by spectroscopic data. The absolute configuration of
      the 7,8-diol moiety in 1 was assigned by CD data after addition of Mo2(OAc)4 in
      dimethyl sulfoxide (DMSO) solution. Compounds 1 and 2 exhibited weak activity of
      anti-platelet aggregation in vitro. 

PMID- 24749562
TI  - EGR1 supports the osteogenic differentiation of dental stem cells.
AB  - AIM: To evaluate whether and how the transcription factor early growth response
      gene 1 (EGR1) affects the osteogenic differentiation of dental stem cells.
      METHODOLOGY: Dental stem cells from apical papilla (SCAPs) and from the dental
      follicle (DFCs) were transfected with EGR1-specific siRNA or EGR-1 expression
      plasmid. Gene regulation was verified at protein level by Western blotting. The
      expression of the transcription factors distal-less homeobox 3 (DLX3), alkaline
      phosphatase (ALP) and bone morphogenetic protein 2 (BMP2), which are all
      regulators and markers of the osteogenic differentiation in dental stem cells,
      was determined by quantitative reverse transcription-polymerase chain reaction
      (qRT-PCR). To investigate mineralization, SCAP long-term cultures were stained
      with alizarin red after EGR1 over-expression. RESULTS: EGR1 was induced in SCAPs
      during osteogenic differentiation. DLX3 and bone morphogenetic protein 2 (BMP2)
      were up-regulated after EGR1 over-expression and down-regulated after EGR1
      depletion. The expression of ALP was also down-regulated after EGR1 depletion.
      The over-expression of EGR1 in SCAPs promoted mineralization after osteogenic
      differentiation. CONCLUSIONS: EGR1 supported the osteogenic differentiation of
      dental stem cells by potentially regulating the expression of DLX3 and BMP2.

PMID- 24749563
TI  - Insulin pump therapy in youth with type 1 diabetes: toward closed-loop systems.
AB  - INTRODUCTION: Insulin pump technology has advanced considerably over the past
      three decades, leading to more favorable metabolic control and less hypoglycemic
      events when compared with multiple daily injection therapy. The use of insulin
      pumps is increasing, particularly in children and adolescents with type 1
      diabetes. AREAS COVERED: This review outlines recent developments in insulin pump
      therapy from a pediatric perspective. 'Smart' pumps, sensor-augmented pump
      therapy and threshold-suspend feature of insulin pumps are reviewed in terms of
      efficacy, safety and psychosocial impact. The current status of closed-loop
      systems focusing on clinical outcomes is highlighted. EXPERT OPINION: Closed-loop
      insulin delivery is gradually progressing from bench to the clinical practice.
      Longer and larger studies in home settings are needed to expand on short- to
      medium-term outpatient evaluations. Predictive low glucose management and
      overnight closed-loop delivery may be the next applications to be implemented in
      daily routine. Further challenges include improvements of control algorithms,
      sensor accuracy, duration of insulin action, integration and size of devices and
      connectivity and usability. Gradual improvements and increasing sophistication of
      closed-loop components lie on the path toward unsupervised hands-off fully closed
      loop system.

PMID- 24749564
TI  - Weekly radiotherapy for basal cell carcinoma in the frail and elderly.

PMID- 24749565
TI  - A new format, but with quality still to the fore.

PMID- 24749566
TI  - Regulator urges staff to do more to prevent 'avoidable' infections.

PMID- 24749567
TI  - Using 'offensive' waste bags more often would save money, RCN advises.

PMID- 24749568
TI  - Union to ballot members on pay to end 'hand to mouth' existence.

PMID- 24749569
TI  - Campaign launched to prevent hike in NMC registration fees.

PMID- 24749570
TI  - Should nurses be loyal to the pay review body?

PMID- 24749571
TI  - Unison head accuses Hunt of peddling staffing untruths.
AB  - Poor staffing has reached 'epidemic' levels, leaving thousands of often
      vulnerable patients without the care they need. 

PMID- 24749573
TI  - NICE standards outline role nurses could play in cardiovascular events.

PMID- 24749578
TI  - Shape of Caring review aims to improve training.

PMID- 24749579
TI  - Be firm and ask for more says nurse practitioner.

PMID- 24749587
TI  - Cancer-related lymphoedema.

PMID- 24749581
TI  - Safety in staff numbers - the signs that focus attention on nursing.

PMID- 24749588
TI  - 12 hours: the long and the short of it.

PMID- 24749589
TI  - A cure for crime.

PMID- 24749590
TI  - A winning combination.

PMID- 24749591
TI  - Recipe for change.

PMID- 24749592
TI  - Sole searching.

PMID- 24749593
TI  - Voices - Nursing workforce needs to have more BME managers, says Yvonne Coghill.

PMID- 24749594
TI  - Quiet please.

PMID- 24749595
TI  - Universal values.

PMID- 24749596
TI  - The true value of a hashtag.

PMID- 24749597
TI  - Starting out - an awkward talk about pregnancy kept me from being judgemental.

PMID- 24749603
TI  - Phlebotomy in the community takes pressure off hospitals.

PMID- 24749604
TI  - Lab staff to take industrial action over 24/7 shift pattern.

PMID- 24749605
TI  - If we kept to our contracted hours, it would feel like working part-time.

PMID- 24749606
TI  - Incinerator helps out where a crematorium cannot tread.

PMID- 24749607
TI  - Swan launches action plan for better mental health services.

PMID- 24749609
TI  - Black and minority ethnic staff lose out during restructuring.

PMID- 24749612
TI  - Reducing burnout in nurses and care workers in secure settings.
AB  - AIM: To identify which educational interventions reduce burnout and promote
      wellbeing in nurses and care workers in secure settings. METHOD: A systematic
      review of health, educational and criminal justice literature was undertaken to
      appraise relevant studies and identify educational interventions that were
      effective in reducing burnout. FINDINGS: There is some evidence that clinical
      supervision and psychological intervention training are successful in reducing
      burnout in nurses and care workers in secure settings. CONCLUSION: Supportive
      relationships can help nurses to manage emotional stress, and continuing personal
      and professional development can reduce burnout in qualified nurses in secure
      settings.

PMID- 24749613
TI  - Responding to domestic violence in acute hospital settings.
AB  - Domestic violence is recognised as a significant global health and societal
      concern. It is associated with physical and emotional effects, and individuals
      may present to a range of healthcare providers. There has been a paucity of
      evidence regarding effective strategies for the identification and support of
      patients who have experienced domestic violence, particularly in acute healthcare
      environments, until recently. This article describes the development and
      implementation of a domestic abuse nurse specialist role within one acute
      hospital trust. The wider implications for staff education and training are also
      considered. 

PMID- 24749614
TI  - Cerebral aneurysm and aneurysmal subarachnoid haemorrhage.
AB  - A cerebral aneurysm is a weak or thin spot on a blood vessel in the brain that
      swells and fills with blood. Rupture of a cerebral aneurysm, known as aneurysmal
      subarachnoid haemorrhage, is a medical emergency and is associated with increased
      mortality. This article explores the anatomy and physiology of the brain and
      blood vessels. Current research and guidelines are used to highlight risk factors
      for cerebral aneurysms and their rupture and to discuss best practice for
      treating both. The article provides information on the management and
      complications of the condition, alongside nursing considerations, long-term care,
      discharge and rehabilitation. 

PMID- 24749615
TI  - Suicidal intent.

PMID- 24749616
TI  - Whistleblowers United.

PMID- 24749617
TI  - Could a robot do your job?

PMID- 24749619
TI  - Student life - From student to staff nurse.

PMID- 24749622
TI  - Atomistic molecular dynamics simulations of CO2 diffusivity in H2O for a wide
      range of temperatures and pressures.
AB  - Molecular dynamics simulations were employed for the calculation of diffusion
      coefficients of CO2 in H2O. Various combinations of existing force fields for H2O
      (SPC, SPC/E, and TIP4P/2005) and CO2 (EPM2 and TraPPE) were tested over a wide
      range of temperatures (283.15 K < T < 623.15 K) and pressures (0.1 MPa < P <
      100.0 MPa). All force-field combinations qualitatively reproduce the trends of
      the experimental data; however, two specific combinations were found to be more
      accurate. In particular, at atmospheric pressure, the TIP4P/2005-EPM2 combination
      was found to perform better for temperatures lower than 323.15 K, while the SPC/E
      TraPPE combination was found to perform better at higher temperatures. The
      pressure dependence of the diffusion coefficient of CO2 in H2O at constant
      temperature is shown to be negligible at temperatures lower than 473.15 K, in
      good agreement with experiments. As temperature increases, the pressure effect
      becomes substantial. The phenomenon is driven primarily by the higher
      compressibility of liquid H2O at near-critical conditions. Finally, a simple
      power-law-type phenomenological equation is proposed to correlate the simulation
      values; the proposed correlation should be useful for engineering calculations. 

PMID- 24749624
TI  - Utility of redundant combinatorial libraries in distinguishing high and low
      quality screening hits.
AB  - Large one-bead one-compound (OBOC) combinatorial libraries can be constructed
      relatively easily by solid-phase split and pool synthesis. The use of resins with
      hydrophilic surfaces, such as TentaGel, allows the beads to be used directly in
      screens for compounds that bind selectively to labeled proteins, nucleic acids,
      or other biomolecules. However, we have found that this method, while useful, has
      a high false positive rate. In other words, beads that are scored as hits often
      display compounds that prove to be poor ligands for the target of interest when
      they are resynthesized and carried through validation trials. This results in a
      significant waste of time and resources in cases where putative hits cannot be
      validated without resynthesis. Here, we report that this problem can be largely
      eliminated through the use of redundant OBOC libraries, where more than one bead
      displaying the same compound is present in the screen. We show that compounds
      isolated more than once are likely to be high quality ligands for the target of
      interest, whereas compounds isolated only once have a much higher likelihood of
      being poor ligands. While the use of redundant libraries does limit the number of
      unique compounds that can be screened at one time in this format, the overall
      savings in time, effort, and materials makes this a more efficient route to the
      isolation of useful ligands for biomolecules. 

PMID- 24749623
TI  - Differential conformational dynamics in the closely homologous FK506-binding
      domains of FKBP51 and FKBP52.
AB  - As co-chaperones of Hsp90 (heat-shock protein 90), FKBP51 (FK506-binding protein
      of 51 kDa) and FKBP52 (FK506-binding protein of 52 kDa) act as antagonists in
      regulating the hormone affinity and nuclear transport of steroid receptor
      complexes. Exchange of Leu119 in FKBP51 for Pro119 in FKBP52 has been shown to
      largely reverse the steroid receptor activities of FKBP51 and FKBP52. To examine
      whether differences in conformational dynamics/plasticity might correlate with
      changes in the reported receptor activities, 15N-NMR relaxation measurements were
      carried out on the N-terminal FKBP domains of FKBP51 and FKBP52 as well as their
      residue-swapped variants. Both proteins exhibit a similar pattern of motion in
      the picosecond-nanosecond timeframe as well as a small degree of 15N line
      broadening, indicative of motion in the microsecond-millisecond timeframe, in the
      beta3a strand of the central sheet. Only the FKBP51 domain exhibits much larger
      line-broadening in the adjacent beta3 bulge (40's loop of FKBP12) and throughout
      the long beta4-beta5 loop (80's loop of FKBP12). The L119P mutation at the tip of
      the beta4-beta5 loop completely suppressed the line-broadening in this loop while
      partially suppressing the line-broadening in the neighbouring beta2 and beta3a
      strands. The complementary P119L and P119L/P124S variants of FKBP52 yielded
      similar patterns of line-broadening for the beta4-beta5 loop as that for FKBP51,
      although only 20% and 60% as intense respectively. However, despite the close
      structural similarity in the packing interactions between the beta4-beta5 loop
      and the beta3a strand for FKBP51 and FKBP52, the line-broadening in the beta3a
      strand is unaffected by the P119L or P119L/P124S mutations in FKBP52. 

PMID- 24749625
TI  - Influence of the source of incisional vitreous incarceration on sclerotomy
      closure competency after transconjunctival sutureless vitrectomy.
AB  - PURPOSE: To evaluate the influence that the origin of incisional vitreous
      incarceration may have on the presence of postoperative conjunctival blebs over
      sclerotomies after transconjunctival sutureless vitrectomy (TSV). Blebs are
      formed by incisional leakage due to incompetent closure. METHODS: Twenty-three
      gauge TSV was performed in 83 cadaveric pig eyes. Once each vitrectomy was
      finished, ultrasound biomicroscopy (UBM) was used to assess the presence of
      postoperative conjunctival blebs over the sclerotomy sites, as well as the
      existence of vitreous incarcerated in incisions. Vitreous strands may come from
      the perisclerotomy area, running parallel to the sclera toward the inner hole of
      the sclerotomies, or may radiate from the core of the vitreous cavity. RESULTS:
      Vitreous entrapment was found in 73.9% of the sclerotomies; 43.4% of the
      incisions showed vitreous strands coming parallel to the sclera (12.9% of them
      showed conjunctival bleb), 19.7% of the wounds presented vitreous aiming toward
      the core of the vitreous cavity (2% of them had conjunctival bleb) and 10.8% of
      the entrances presented both vitreous incarceration sources (none of them showed
      bleb). Incisions with vitreous entrapment parallel to the sclera were associated
      with a significantly greater sclerotomy leakage rate. CONCLUSIONS: Sclerotomies
      with vitreous incarceration coming from the core of the vitreous cavity showed a
      greater incisional closure competency than that observed in incisions with
      vitreous entrapment coming from the pericannular area; if these results were
      confirmed in humans, different postoperative suture rates may be expected on
      sclerotomies according to the vitrectomy degree performed in different areas of
      the vitreous cavity.

PMID- 24749626
TI  - Trait-mediated functional responses: predator behavioural type mediates prey
      consumption.
AB  - The predator functional response (i.e. per capita consumption rate as a function
      of prey density) is central to our understanding of predator-prey population
      dynamics. This response is behavioural, depending on the rate of attack and time
      it takes to handle prey. Consistent behavioural differences among conspecific
      individuals, termed behavioural types, are a widespread feature of predator and
      prey populations but the effects of behavioural types on the functional response
      remain unexplored. We tested the effects of crab (Panopeus herbstii) behavioural
      type, specifically individual activity level, on the crab functional response to
      mussel (Brachidontes exustus) prey. We further tested whether the effects of
      activity level on the response are mediated by the presence of toadfish (Opsanus
      tau) predation threat in the form of waterborne chemical cues known to reduce
      crab activity level. The effects of crab activity level on the functional
      response were dependent on crab body size. Individual activity level increased
      the magnitude (i.e. slope and asymptote) of the type II functional response of
      small crabs, potentially through an increase in time spent foraging, but had no
      effect on the functional response of large crabs. Predation threat did not
      interact with activity level to influence mussel consumption, but independently
      reduced the slope of the type II functional response. Overall, this study
      demonstrates size-specific effects of a behavioural type on a predator-prey
      interaction, as well as a general pathway (modification of the functional
      response) by which the effects of individual behavioural types can scale up to
      influence predator-prey population dynamics. 

PMID- 24749627
TI  - Infants segment continuous events using transitional probabilities.
AB  - Throughout their 1st year, infants adeptly detect statistical structure in their
      environment. However, little is known about whether statistical learning is a
      primary mechanism for event segmentation. This study directly tests whether
      statistical learning alone is sufficient to segment continuous events. Twenty
      eight 7- to 9-month-old infants viewed a sequence of continuous actions performed
      by a novel agent in which there were no transitional movements that could have
      constrained the possible upcoming actions. At test, infants distinguished
      statistically intact units from less predictable ones. The ability to segment
      events using statistical structure may help infants discover other cues to event
      boundaries, such as intentions, and carve up the world of continuous motion in
      meaningful ways. 

PMID- 24749628
TI  - Examining the lag effect under incidental encoding: contributions of semantic
      priming and reminding.
AB  - Memory is better when repeated learning events are spaced than when they are
      massed (spacing effect), as well as when material is processed semantically than
      when it is processed graphemically (levels-of-processing effect). Examination of
      the relationship between levels of processing and spacing for both deeply and
      shallowly encoded items has shown a spacing effect for items processed deeply,
      but not shallowly. A semantic priming account of spacing was proposed to explain
      the interaction between levels of processing and spacing on memory. The current
      study manipulated levels of processing and the amount of spacing (lag) that
      occurred between repetitions of items that were incidentally encoded. Results
      from Experiments 1A and 1B revealed lag effects in test performance when items
      were deeply and shallowly encoded. Although these findings are inconsistent with
      a semantic priming account, they can be interpreted within a reminding account,
      which is explored in Experiment 2. Results from the second experiment indicate
      that bringing reminding under conscious control benefited items that were
      presented at a long lag but not at a shorter lag. Together, this study provides
      evidence that is difficult to accommodate with a semantic priming account of
      spacing and instead provides additional support for a reminding account
      suggesting that automatic and controlled processes may both underlie the
      reminding process. 

PMID- 24749629
TI  - Evaluation of in vivo behavior of ameroid ring constrictors in dogs with
      congenital extrahepatic portosystemic shunts using computed tomography.
AB  - OBJECTIVE: To evaluate the in vivo pattern of ameroid constrictor closure of
      congenital extrahepatic portosystemic shunts in dogs. STUDY DESIGN: Prospective
      study. ANIMALS: Dogs (n = 22) with congenital extrahepatic portosystemic shunts.
      METHODS: Contrast-enhanced computed tomography was performed immediately before,
      and at least 8 weeks after placement of ameroid ring constrictors. Plastic
      encased ameroid constrictors were used in 17 dogs and metal constrictors in 5
      dogs. Presence of residual flow through the portosystemic shunt, additional
      anomalous vessels, acquired shunts and soft tissue associated with the ameroid
      constrictor was recorded. Postoperative internal diameter was recorded for the 17
      plastic constrictors. Correlations between internal diameter and pre- and
      postoperative serum protein concentration were analyzed. RESULTS: No ameroid
      constrictor closed completely: shunt occlusion was always dependent on soft
      tissue within the ameroid ring. Residual flow through the shunt was present in 4
      dogs (18%), although this caused persistent elevation of shunt fraction in only 1
      dog (dog 8). The change in ameroid constrictor internal diameter was not
      significantly correlated with serum protein concentration. CONCLUSIONS: Complete
      shunt occlusion after AC placement is usually dependent on soft tissue reaction.
      Ameroid constrictors >=5 mm diameter may not promote complete shunt occlusion.

PMID- 24749630
TI  - Target-catalyzed dynamic assembly-based pyrene excimer switching for enzyme-free
      nucleic acid amplified detection.
AB  - Because of the intrinsic importance of nucleic acid as biotargets, the simple and
      sensitive detection of nucleic acid is very essential for biological studies and
      medical diagnostics. Herein, a new strategy for enzyme-free nucleic acid
      amplified detection has been opened up by combining the signal-amplification
      capability of target-catalyzed dynamic assembly with the spatially sensitive
      fluorescent signal of the pyrene excimer. In this strategy, three metastable
      pyrene-labeled hairpin DNA probes were designed as assembly components, which
      were kinetically handicapped from cross-opening in the absence of the target DNA.
      However, in the presence of the target, the dynamic assembly of branched
      junctions was circularly catalyzed and accompanied by the switching of the pyrene
      excimer which emits at ~488 nm. Thus, the target DNA could be detected by this
      simple mix-and-detect amplification method, without expensive and perishable
      protein enzymes. A good detection capability exhibited with a detectable minimum
      target concentration of 10 pM, which was comparable to or even better than some
      reported enzyme-dependent amplification methods, and the potential for the target
      detection from complex fluids was verified. In addition, as a novel
      transformation of dynamic DNA assembly technology into enzyme-free signal
      amplification analytical application, we infer that the proposed strategy will
      hold promising potential for application in a wider range of fields, including
      aptamer-based non-nucleic acid target sensing, biomedicine, and bioimaging.

PMID- 24749631
TI  - Whole exome sequencing to estimate alloreactivity potential between donors and
      recipients in stem cell transplantation.
AB  - Whole exome sequencing (WES) was performed on stem cell transplant donor
      recipient (D-R) pairs to determine the extent of potential antigenic variation at
      a molecular level. In a small cohort of D-R pairs, a high frequency of sequence
      variation was observed between the donor and recipient exomes independent of
      human leucocyte antigen (HLA) matching. Nonsynonymous, nonconservative single
      nucleotide polymorphisms were approximately twice as frequent in HLA-matched
      unrelated, compared with related D-R pairs. When mapped to individual
      chromosomes, these polymorphic nucleotides were uniformly distributed across the
      entire exome. In conclusion, WES reveals extensive nucleotide sequence variation
      in the exomes of HLA-matched donors and recipients. 

PMID- 24749632
TI  - What accounts for the rapid detection of threat? Evidence for an advantage in
      perceptual and behavioral responding from eye movements.
AB  - Countless studies have reported that adults detect a variety of threatening
      stimuli more quickly than positive or neutral stimuli. Despite speculation about
      what factors drive this bias in detection, very few studies have examined the
      exact search strategies adults use to detect threatening stimuli in visual
      search. The current research uses an eye-tracker in a classic visual search
      paradigm in attempt to elucidate the factors that lead to rapid threat detection.
      Our results replicate previous work, demonstrating that adults detect threatening
      targets (snakes and spiders) more quickly and accurately than nonthreatening
      targets (flowers and mushrooms). Results from the eye-tracker extend these
      findings, suggesting that the bias for threat in detection tasks is driven by
      both an advantage in perception, or bottom up processing (faster fixations to
      threats vs. nonthreats), and an advantage in behavioral responding, or top down
      processing (faster behavioral responding to threats once a target is first
      fixated). Together, the results present a more complete picture of the mechanisms
      that drive rapid threat detection, suggesting that multiple factors can lead to
      an advantage for threat in visual search.

PMID- 24749633
TI  - Evidence for cultural dialects in vocal emotion expression: acoustic
      classification within and across five nations.
AB  - The possibility of cultural differences in the fundamental acoustic patterns used
      to express emotion through the voice is an unanswered question central to the
      larger debate about the universality versus cultural specificity of emotion. This
      study used emotionally inflected standard-content speech segments expressing 11
      emotions produced by 100 professional actors from 5 English-speaking cultures.
      Machine learning simulations were employed to classify expressions based on their
      acoustic features, using conditions where training and testing were conducted on
      stimuli coming from either the same or different cultures. A wide range of
      emotions were classified with above-chance accuracy in cross-cultural conditions,
      suggesting vocal expressions share important characteristics across cultures.
      However, classification showed an in-group advantage with higher accuracy in
      within- versus cross-cultural conditions. This finding demonstrates cultural
      differences in expressive vocal style, and supports the dialect theory of
      emotions according to which greater recognition of expressions from in-group
      members results from greater familiarity with culturally specific expressive
      styles.

PMID- 24749634
TI  - A contextual approach to experiential avoidance and social anxiety: evidence from
      an experimental interaction and daily interactions of people with social anxiety
      disorder.
AB  - Experiential avoidance (EA), the tendency to avoid internal, unwanted thoughts
      and feelings, is hypothesized to be a risk factor for social anxiety. Existing
      studies of experiential avoidance rely on trait measures with minimal contextual
      consideration. In two studies, we examined the association between experiential
      avoidance and anxiety within real-world social interactions. In the first study,
      we examined the effect of experiential avoidance on social anxiety in everyday
      life. For 2 weeks, 37 participants with Social Anxiety Disorder (SAD) and 38
      healthy controls provided reports of experiential avoidance and social anxiety
      symptoms during face-to-face social interactions. Results showed that momentary
      experiential avoidance was positively related to anxiety symptoms during social
      interactions and this effect was stronger among people with SAD. People low in EA
      showed greater sensitivity to the level of situational threat than high EA
      people. In the second study, we facilitated an initial encounter between
      strangers. Unlike Study 1, we experimentally created a social situation where
      there was either an opportunity for intimacy (self-disclosure conversation) or no
      such opportunity (small-talk conversation). Results showed that greater
      experiential avoidance during the self-disclosure conversation temporally
      preceded increases in social anxiety for the remainder of the interaction; no
      such effect was found in the small-talk conversation. Our findings provide
      insight into the association between experiential avoidance on social anxiety in
      laboratory and naturalistic settings, and demonstrate that the effect of EA
      depends upon level of social threat and opportunity.

PMID- 24749636
TI  - Psychological "gel" to bind individuals' goal pursuit: gratitude facilitates goal
      contagion.
AB  - Past research demonstrates that gratitude affects individuals' self-regulation of
      behavior primarily through engendering a prosocial tendency. Based on theories
      proposing that gratitude plays an unique role in fostering communal relationship
      (e.g., Algoe, 2012), we propose that gratitude can have an incidental effect in
      facilitating goal contagion: automatically inferring and adopting the goal
      implied by a social other's behavior. This hypothesis is supported in 3 studies.
      In Study 1, after being exposed to the behaviors of a social target that implied
      either a cooperative or a competitive goal, individuals adopted the respective
      goal and behaved accordingly in a Resource Dilemma Task. This occurred, however,
      only when they were feeling gratitude and not when they were feeling joy or a
      neutral mood. In Study 2, after being exposed to a social target's behavior that
      implied the goal to make money, people feeling gratitude, as compared to those
      feeling pride or a neutral mood, strove for a future opportunity to earn money.
      Study 3 further demonstrated that individuals' goal striving behavior was
      mediated by a heightened level of goal activation. Finally, it was found that
      gratitude facilitated goal contagion only when the social target was a member of
      participants' own social group. Through this mechanism, gratitude, thus, seems to
      bind one's self-regulation with those of social others. Theoretical and practical
      implications of this new perspective are discussed.

PMID- 24749635
TI  - When seeing is more than looking: Intentional gaze modulates object desirability.
AB  - Objects in the environment have a perceived value that can be changed through
      social influence. A subtle way to influence object evaluation is through eye
      gaze: Objects looked at by others are perceived as more likable than objects that
      are not looked at. In 3 experiments, we directly tested the hypothesis that this
      liking effect depends on the processing of the intentional relation between
      other's eye gaze and the object being looked at. To this end, we used a novel
      paradigm in which participants observed a face looking left or right behind an
      opaque barrier. Under all tested conditions, we found a gaze cueing effect on
      attention: Looked-at objects were categorized faster than looked-away objects. In
      contrast, observed gaze only led to a boost in affective evaluation for the
      target object when observers had the impression that the face could see the
      object behind the barrier, but not when observers had the impression that the
      face could not see the object. These findings indicate that observers make a
      sophisticated use of social gaze cues in the affective evaluation of objects:
      Objects looked at by others are liked more than objects looked away but only when
      others can see the objects.

PMID- 24749637
TI  - Multiple emotions: a person-centered approach to the relationship between
      intergroup emotion and action orientation.
AB  - Although a great deal of research has investigated the relationship between
      emotions and action orientations, most studies to date have used variable
      centered techniques to identify the best emotion predictor(s) of a particular
      action. Given that people frequently report multiple or blended emotions, a
      profitable area of research may be to adopt person-centered approaches to examine
      the action orientations elicited by a particular combination of emotions or
      "emotion profile." In two studies, across instances of intergroup inequality in
      Australia and Canada, we examined participants' experiences of six intergroup
      emotions: sympathy, anger directed at three targets, shame, and pride. In both
      studies, five groups of participants with similar emotion profiles were
      identified by cluster analysis and their action orientations were compared;
      clusters indicated that the majority of participants experienced multiple
      emotions. Each action orientation was also regressed on the six emotions. There
      were a number of differences in the results obtained from the person-centered and
      variable-centered approaches. This was most apparent for sympathy: the group of
      participants experiencing only sympathy showed little inclination to perform
      prosocial actions, yet sympathy was a significant predictor of numerous action
      orientations in regression analyses. These results imply that sympathy may only
      prompt a desire for action when experienced in combination with other emotions.
      We suggest that the use of person-centered and variable-centered approaches as
      complementary analytic strategies may enrich research into not only the affective
      predictors of action, but emotion research in general.

PMID- 24749638
TI  - If looks could kill: anger attributions are intensified by affordances for doing
      harm.
AB  - Emotion perception is necessarily imprecise, leading to possible overperception
      or underperception of a given emotion extant in a target individual. When the
      costs of these two types of errors are recurrently asymmetrical, categorization
      mechanisms can be expected to be biased to commit the less costly error.
      Contextual factors can influence this asymmetry, resulting in a concomitant
      increase in biases in the perception of a given emotion. Anger motivates
      aggression, hence an important contextual factor in anger perception is the
      capacity of the perceived individual to inflict harm. The greater the capacity to
      harm, the more costly it is to underestimate the extent to which the target is
      angry, and therefore the more that perception should be biased in favor of
      overestimation. Consonant with this prediction, in two studies, U.S. adults
      perceived greater anger when models were holding household objects having
      affordances as weapons (e.g., garden shears) than when they were holding objects
      lacking such affordances (e.g., a watering can) or were empty-handed. Consistent
      with the unique relationship between anger and aggression, this positive bias did
      not appear in judgments of other negative emotions.

PMID- 24749639
TI  - Motherhood and oxytocin receptor genetic variation are associated with selective
      changes in electrocortical responses to infant facial expressions.
AB  - Recent studies suggest that parental caregiving is associated with adaptive
      changes in neurocognitive responses to emotional cues and oxytocin function,
      possibly reflecting the increased need of parents to monitor infants' emotional
      states. In the current study, we investigated whether the changes associated with
      motherhood and oxytocin receptor genetic variation rs53576 are specific to the
      processing of infant cues as opposed to a more general increase in responsiveness
      to emotional cues. We measured event-related brain potentials (ERPs) and
      behavioral recognition responses from mothers of young infants (n = 48) and
      nulliparous females (n = 46) to infant and adult faces displaying strong and mild
      intensity emotional expressions. Mothers and GG allele carriers of the OXTR gene
      showed an early latency (~100 ms) differential frontal ERP response to strong
      intensity facial expressions, and mothers also showed modulation of the posterior
      EPN waveform by negative valence. The early frontal ERP modulation was associated
      with faster emotion recognition performance across participants. Most
      importantly, these effects were highly specific to infant facial expressions. The
      results point to a dissociable neurocognitive system that is involved in
      monitoring infants' emotional cues and may be important in supporting parental
      caregiving in humans.

PMID- 24749640
TI  - Listen to your heart: the cultural shaping of interoceptive awareness and
      accuracy.
AB  - West African cultural contexts foster higher levels of attention to the bodily
      signals compared with the European American contexts. Interoception, or the
      processing of signals from the body, is a key component of emotional reactivity.
      Interoceptive awareness (i.e., the self-reported tendency to attend to
      physiological changes) and accuracy (i.e., the ability to accurately detect
      physiological changes) are distinct aspects of interoception. Does the West
      African cultural emphasis on interoceptive awareness affect individuals'
      abilities to accurately perceive physiological changes in response to emotional
      stimuli? West African and European American young adults watched a fear-inducing
      film clip and continuously rated their perception of heart rate changes in
      response to the clip. Actual heart rates were also recorded continuously. Cross
      correlations were calculated between measures of perceived and actual heart rate.
      Although average levels of coherence between these measures were low across
      groups, West Africans showed higher levels of interoceptive awareness, but lower
      levels of interoceptive accuracy than European Americans. These results suggest
      that cultural scripts of attending to the body may affect coupling between actual
      and perceived physiological reactivity in the context of emotions. These results
      have implications for studying cultural shaping of somatic presentation of mood
      and anxiety disorders.

PMID- 24749641
TI  - A cultural perspective on emotional experiences across the life span.
AB  - Past research suggests that older adults place a greater priority on goals of
      maintaining positive experiences and distancing from negative experiences. We
      hypothesized that these aging-related differences in emotional experiences are
      more pronounced in Western cultures that encourage linear approaches to well
      being compared with Eastern cultures that encourage more dialectic approaches to
      well-being. We compared reports of positive and negative emotional experiences
      from random samples of Americans (a culture characterized by focus on positive
      and distancing from negative experiences) and Japanese (a culture characterized
      by its endorsement of dialectical experiences). In support of our hypothesis,
      older Americans reported significantly less negative emotions in unpleasant
      situations, relative to their younger counterparts. Furthermore, both trait-level
      negativity (i.e., rumination) and interpersonal negativity (i.e., recall of
      unpleasant relationships and intensity of an unpleasant interpersonal experience)
      were lower among older compared with younger Americans. In contrast, such aging
      related effects were absent in the Japanese respondents. Even though older and
      younger Japanese reported the same amount of negative emotions in unpleasant
      situations, older Japanese also reported more positive emotions in the same
      unpleasant situations. Together, these findings highlight the role of culture for
      understanding how emotional experiences unfold across adulthood.

PMID- 24749642
TI  - Rethinking butterflies: the affective, physiological, and performance effects of
      reappraising arousal during social evaluation.
AB  - This study examined the effects of reappraising stress arousal on affective
      displays, physiological responses, and social performance during an evaluative
      situation. Participants were sampled from across the social anxiety spectrum and
      instructed to reappraise arousal as beneficial or received no instructions.
      Independent raters coded affective displays, nonverbal signaling, and speech
      performance. Saliva samples collected at baseline and after evaluation were
      assayed for salivary alpha-amylase (sAA), a protein that indexes sympathetic
      activation. Arousal reappraisal participants exhibited less shame and anxiety,
      less avoidant nonverbal signaling, and performed marginally better than no
      instruction controls. Reappraisal participants also exhibited increased levels of
      sAA and increased appraisals of coping resources compared with controls.
      Furthermore, stress appraisals mediated relationships between reappraisal and
      affective displays. This research indicates that reframing stress arousal can
      improve behavioral displays of affect during evaluative situations via altering
      cognitive appraisals.

PMID- 24749643
TI  - Is valuing positive emotion associated with life satisfaction?
AB  - The experience of positive emotion is closely linked to subjective well-being.
      For this reason, campaigns aimed at promoting the value of positive emotion have
      become widespread. What is rarely considered are the cultural implications of
      this focus on happiness. Promoting positive emotions as important for "the good
      life" not only has implications for how individuals value these emotional states,
      but for how they believe others around them value these emotions also. Drawing on
      data from over 9,000 college students across 47 countries we examined whether
      individuals' life satisfaction is associated with living in contexts in which
      positive emotions are socially valued. The findings show that people report more
      life satisfaction in countries where positive emotions are highly valued and this
      is linked to an increased frequency of positive emotional experiences in these
      contexts. They also reveal, however, that increased life satisfaction in
      countries that place a premium on positive emotion is less evident for people who
      tend to experience less valued emotional states: people who experience many
      negative emotions, do not flourish to the same extent in these contexts. The
      findings demonstrate how the cultural value placed on certain emotion states may
      shape the relationship between emotional experiences and subjective well-being.

PMID- 24749644
TI  - Comparing effectiveness of palliative care for elderly people in long-term care
      facilities in Europe (PACE). EFPC: European Forum for Primary Care.

PMID- 24749645
TI  - How to address data gaps in life cycle inventories: a case study on estimating
      CO2 emissions from coal-fired electricity plants on a global scale.
AB  - One of the major challenges in life cycle assessment (LCA) is the availability
      and quality of data used to develop models and to make appropriate
      recommendations. Approximations and assumptions are often made if appropriate
      data are not readily available. However, these proxies may introduce uncertainty
      into the results. A regression model framework may be employed to assess missing
      data in LCAs of products and processes. In this study, we develop such a
      regression-based framework to estimate CO2 emission factors associated with coal
      power plants in the absence of reported data. Our framework hypothesizes that
      emissions from coal power plants can be explained by plant-specific factors
      (predictors) that include steam pressure, total capacity, plant age, fuel type,
      and gross domestic product (GDP) per capita of the resident nations of those
      plants. Using reported emission data for 444 plants worldwide, plant level CO2
      emission factors were fitted to the selected predictors by a multiple linear
      regression model and a local linear regression model. The validated models were
      then applied to 764 coal power plants worldwide, for which no reported data were
      available. Cumulatively, available reported data and our predictions together
      account for 74% of the total world's coal-fired power generation capacity. 

PMID- 24749646
TI  - Photochemical dihydrogen production using an analogue of the active site of
      [NiFe] hydrogenase.
AB  - Photoproduction of dihydrogen (H2) by a low molecular weight analogue of the
      active site of [NiFe] hydrogenase has been investigated by reduction of the
      [NiFe2] cluster, 1, by a photosensitier PS (PS = [ReCl(CO)3(bpy)] or
      [Ru(bpy)3][PF6]2). Reductive quenching of the (3)MLCT excited state of the
      photosensitizer by NEt3 or N(CH2CH2OH)3 (TEOA) generates PS(*-), and subsequent
      intermolecular electron transfer to 1 produces the reduced anionic form of 1.
      Time-resolved infrared spectroscopy (TRIR) has been used to probe the
      intermediates throughout the reduction of 1 and subsequent photocatalytic H2
      production from [HTEOA][BF4], which was monitored by gas chromatography. Two
      structural isomers of the reduced form of 1 (1a(*-) and 1b(*-)) were detected by
      Fourier transform infrared spectroscopy (FTIR) in both CH3CN and DMF
      (dimethylformamide), while only 1a(*-) was detected in CH2Cl2. Structures for
      these intermediates are proposed from the results of density functional theory
      calculations and FTIR spectroscopy. 1a(*-) is assigned to a similar structure to
      1 with six terminal carbonyl ligands, while calculations suggest that in 1b(*-)
      two of the carbonyl groups bridge the Fe centers, consistent with the peak
      observed at 1714 cm(-1) in the FTIR spectrum for 1b(*-) in CH3CN, assigned to a
      nu(CO) stretching vibration. Formation of 1a(*-) and 1b(*-) and production of H2
      was studied in CH3CN, DMF, and CH2Cl2. Although the more catalytically active
      species (1a(*-) or 1b(*-)) could not be determined, photocatalysis was observed
      only in CH3CN and DMF. 

PMID- 24749647
TI  - Influence of the HLA characteristics of Italian patients on donor search outcome
      in unrelated hematopoietic stem cell transplantation.
AB  - The information regarding the probability of finding a matched unrelated donor
      (MUD) within a relatively short time is crucial for the success of hematopoietic
      stem cell transplantation (HSCT), particularly in patients with malignancies. In
      this study, we retrospectively analyzed 315 Italian patients who started a search
      for a MUD, in order to assess the distribution of human leukocyte antigen (HLA)
      alleles and haplotypes in this population of patients and to evaluate the
      probability of finding a donor. Comparing two groups of patients based on whether
      or not a 10/10 HLA-matched donor was available, we found that patients who had a
      fully-matched MUD possessed at least one frequent haplotype more often than the
      others (45.6% vs 14.3%; P = 0.000003). In addition, analysis of data pertaining
      to the HLA class I alleles distribution showed that, in the first group of
      patients, less common alleles were under-represented (20.2% vs 40.0%; P = 0.006).
      Therefore, the presence of less frequent alleles represents a negative factor for
      the search for a potential compatible donor being successful, whereas the
      presence of one frequent haplotype represents a positive predictive factor.
      Antigenic differences between patient and donor observed at C and DQB1 loci, were
      mostly represented by particular B/C or DRB1/DQB1 allelic associations. Thus,
      having a particular B or DRB1 allele, linked to multiple C or DQB1 alleles,
      respectively, might be considered to be associated with a lower probability of a
      successful search. Taken together, these data may help determine in advance the
      probability of finding a suitable unrelated donor for an Italian patient. 

PMID- 24749648
TI  - Danger-associated molecular patterns and danger signals in idiopathic pulmonary
      fibrosis.
AB  - The chronic debilitating lung disease, idiopathic pulmonary fibrosis (IPF), is
      characterized by a progressive decline in lung function, with a median mortality
      rate of 2-3 years after diagnosis. IPF is a disease of unknown cause and
      progression, and multiple pathways have been demonstrated to be activated in the
      lungs of these patients. A recent genome-wide association study of more than
      1,000 patients with IPF identified genes linked to host defense, cell-cell
      adhesion, and DNA repair being altered due to fibrosis (Fingerlin, et al. Nat
      Genet 2013;45:613-620). Further emerging data suggest that the respiratory system
      may not be a truly sterile environment, and it exhibits an altered microbiome
      during fibrotic disease (Molyneaux and Maher. Eur Respir Rev 2013;22:376-381).
      These altered host defense mechanisms might explain the increased susceptibility
      of patients with IPF to microbial- and viral-induced exacerbations. Moreover,
      chronic epithelial injury and apoptosis are key features in IPF, which might be
      mediated, in part, by both pathogen-associated (PA) and danger-associated
      molecular patterns (MPs). Emerging data indicate that both PAMPs and danger
      associated MPs contribute to apoptosis, but not necessarily in a manner that
      allows for the removal of dying cells, without further exacerbating inflammation.
      In contrast, both types of MPs drive cellular necrosis, leading to an
      exacerbation of lung injury and/or infection as the debris promotes a
      proinflammatory response. Thus, this Review focuses on the impact of MPs
      resulting from infection-driven apoptosis and necrosis during chronic fibrotic
      lung disease. 

PMID- 24749649
TI  - Nanoparticle albumin-bound paclitaxel (nab-paclitaxel): extending its
      indications.

PMID- 24749650
TI  - Chelate effects in glyme/lithium bis(trifluoromethanesulfonyl)amide solvate ionic
      liquids. I. Stability of solvate cations and correlation with electrolyte
      properties.
AB  - To develop a basic understanding of a new class of ionic liquids (ILs), "solvate"
      ILs, the transport properties of binary mixtures of lithium
      bis(trifluoromethanesulfonyl)amide (Li[TFSA]) and oligoethers (tetraglyme (G4),
      triglyme (G3), diglyme (G2), and monoglyme (G1)) or tetrahydrofuran (THF) were
      studied. The self-diffusion coefficient ratio of the solvents and Li(+) ions
      (Dsol/DLi) was a good metric for evaluating the stability of the complex cations
      consisting of Li(+) and the solvent(s). When the molar ratio of Li(+) ions and
      solvent oxygen atoms ([O]/[Li(+)]) was adjusted to 4 or 5, Dsol/DLi always
      exceeded unity for THF and G1-based mixtures even at the high concentrations,
      indicating the presence of uncoordinating or highly exchangeable solvents. In
      contrast, long-lived complex cations were evidenced by a Dsol/DLi ~ 1 for the
      longer G3 and G4. The binary mixtures studied were categorized into two different
      classes of liquids: concentrated solutions and solvate ILs, based on Dsol/DLi.
      Mixtures with G2 exhibited intermediate behavior and are likely the borderline
      dividing the two categories. The effect of chelation on the formation of solvate
      ILs also strongly correlated with electrolyte properties; the solvate ILs showed
      improved thermal and electrochemical stability. The ionicity
      (Lambdaimp/LambdaNMR) of [Li(glyme or THF)x][TFSA] exhibited a maximum at an
      [O]/[Li(+)] ratio of 4 or 5. 

PMID- 24749651
TI  - Post-traumatic immunosuppression is reversed by anti-coagulated salvaged blood
      transfusion: deductions from studying immune status after knee arthroplasty.
AB  - Major trauma increases vulnerability to systemic infections due to poorly defined
      immunosuppressive mechanisms. It confers no evolutionary advantage. Our objective
      was to develop better biomarkers of post-traumatic immunosuppression (PTI) and to
      extend our observation that PTI was reversed by anti-coagulated salvaged blood
      transfusion, in the knowledge that others have shown that non-anti-coagulated
      (fibrinolysed) salvaged blood was immunosuppressive. A prospective non-randomized
      cohort study of patients undergoing primary total knee arthroplasty included 25
      who received salvaged blood transfusions collected post-operatively into acid
      citrate-dextrose anti-coagulant (ASBT cohort), and 18 non-transfused patients
      (NSBT cohort). Biomarkers of sterile trauma included haematological values,
      damage-associated molecular patterns (DAMPs), cytokines and chemokines. Salvaged
      blood was analysed within 1 and 6 h after commencing collection. Biomarkers were
      expressed as fold-changes over preoperative values. Certain biomarkers of sterile
      trauma were common to all 43 patients, including supranormal levels of:
      interleukin (IL)-6, IL-1-receptor-antagonist, IL-8, heat shock protein-70 and
      calgranulin-S100-A8/9. Other proinflammatory biomarkers which were subnormal in
      NSBT became supranormal in ASBT patients, including IL-1beta, IL-2, IL-17A,
      interferon (IFN)-gamma, tumour necrosis factor (TNF)-alpha and annexin-A2.
      Furthermore, ASBT exhibited subnormal levels of anti-inflammatory biomarkers: IL
      4, IL-5, IL-10 and IL-13. Salvaged blood analyses revealed sustained high levels
      of IL-9, IL-10 and certain DAMPs, including calgranulin-S100-A8/9, alpha-defensin
      and heat shock proteins 27, 60 and 70. Active synthesis during salvaged blood
      collection yielded increasingly elevated levels of annexin-A2, IL-1beta, Il-1
      receptor-antagonist, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-17A, IFN-gamma,
      TNF-alpha, transforming growth factor (TGF)-beta1, monocyte chemotactic protein-1
      and macrophage inflammatory protein-1alpha. Elevated levels of high-mobility
      group-box protein-1 decreased. In conclusion, we demonstrated that anti
      coagulated salvaged blood reversed PTI, and was attributed to immune stimulants
      generated during salvaged blood collection.

PMID- 24749652
TI  - Are all risks equal? Early experiences of poverty-related risk and children's
      functioning.
AB  - Using cumulative risk and latent class analysis (LCA) models, we examined how
      exposure to deep poverty (income-to-needs ratio <0.50) and 4 poverty-related
      risks (i.e., single-parent household, residential crowding, caregiver depression,
      and multiple life stressors) in preschool is related to children's future
      difficulty in school in a longitudinal sample of 602 Head Start-enrolled, low
      income families. Results from the LCA revealed 4 risk profiles: low risk, deep
      poverty and single, single and stressed, and deep poverty and crowded household.
      Tests of measurement invariance across racial/ethnic groups established that,
      although patterns of risk are similar across groups (i.e., risks covary in the
      same way), the prevalence of risk profiles differs. African American families
      were overrepresented in the "deep poverty and single" profile while Latino and
      White families were overrepresented in the "deep poverty and crowded" profile.
      Finally, children's third grade functioning in 3 domains (i.e., academic
      performance, behavior problems, and self-regulatory skills) was predicted using a
      cumulative risk index and LCA-identified risk profiles. Both approaches
      demonstrated that children who experienced higher levels of risk in preschool had
      worse school performance than children with low levels of risk. However, LCA also
      revealed that children who experienced "single and stressed" family settings had
      more behavior problems than low-risk children while children who experienced
      "deep poverty and crowded" family settings had worse academic performance. The
      results indicate that all risks are not equal for children's development and
      highlight the utility of LCA for tailoring intervention efforts to best meet the
      needs of target populations.

PMID- 24749653
TI  - Correlates of male cohabiting partner's involvement in child-rearing tasks in low
      income urban Black stepfamilies.
AB  - Cohabitation is a family structure experienced by many Black children. This study
      examines the link between family relationships (child relationship with mother
      and the cohabiting partner; parent and cohabiting partner relationship) and
      involvement of biologically unrelated male cohabiting partners (MCP) in child
      rearing. The participants were 121 low-income urban Black families consisting of
      a single mother, MCP, and an adolescent (56% female, M age = 13.7). Assessments
      were conducted individually with mothers, MCPs, and adolescents via measures
      administered by interview. MCPs were involved in both domains of child rearing
      assessed (daily child-related tasks and setting limits) and those identified as
      coparents by the mother were more involved in child-rearing tasks than those not
      identified as coparents. Using structural equation modeling (SEM), the mother-MCP
      relationship (both support and conflict) and the adolescent-MCP relationship were
      related to MCP's involvement in both domains of child rearing. The findings
      indicate that MCPs are actively involved in child rearing and family relationship
      variables are associated with their involvement in these tasks.

PMID- 24749654
TI  - Leuconostoc as a Cause of Endophthalmitis Post-intravitreal Injection of
      Ranibizumab.
AB  - PURPOSE: The authors report a case of endophthalmitis after intravitreal
      injection of ranibizumab. METHODS: After searching for extensive laboratory tests
      to isolate the etiologic agent Results: The agent was determined as Leuconostoc
      mesenteroides, gram-positive cocci, vancomycin resistant. DISCUSSION:
      Considerations regarding this bacterium were done by calling attention to its
      rarity, difficulty of isolation, and action on secondary comorbidities as
      opportunistic pathogen.

PMID- 24749655
TI  - Multilocus variable number tandem repeat analysis of Edwardsiella piscicida
      isolates pathogenic to fish.
AB  - This study describes a novel multilocus variable number tandem repeat analysis
      (MLVA) based on six variable number of tandem repeat (VNTR) loci for genotyping
      of 37 Edwardsiella piscicida (previously Edwardsiella tarda) isolates from
      multiple sources. The number of alleles identified for each of the six VNTR loci
      ranged from 3 to 5 with VNTR loci 1 (DI = 0.632) and 3 (DI = 0.644), displaying
      the highest degrees of polymorphism. MLVA typing of the 37 E. piscicida isolates
      resulted in the identification of five major clusters consistent with their
      geographical origins, and were designated as MLVA types I, II, III, IV and V.
      Types III and V were resolved further into subtypes largely consistent with
      outbreak source. An MLVA profile comprising a string of integers representing the
      number of tandem repeats for each allele provided a unique identification for
      each MLVA type and/or strain. The MLVA protocol described in the current study is
      robust, relatively simple, has a higher power of resolution than multilocus
      sequence analysis (MLSA) and is capable of discriminating closely related
      isolates.

PMID- 24749656
TI  - The correlation between fluid transport and push-out strength in root canals
      filled with a methacrylate-based filling material.
AB  - AIM: To investigate the correlation between fluid transport and dislocation
      resistance in canals filled with a methacrylate-based filling material.
      METHODOLOGY: The root canals in sixty-five single-rooted human teeth were
      prepared to size 40, 0.06 taper. Sixty roots were filled with a single-cone
      technique using RealSeal SE sealer and divided into 3 groups, whilst five roots
      served as fluid transport positive control. Group 1 (n = 20): correlation group.
      Specimens were consecutively tested with fluid transport for 90 min and
      thereafter with the push-out test at coronal and apical root levels. Group 2 (n =
      20): push-out control. Specimens were only subjected to the push-out test at
      coronal and apical root levels. Group 3 (n = 20): fluid transport negative
      control. Specimens were totally covered with nail varnish. The correlation
      between fluid transport and dislocation resistance was assessed by Kendall's tau
      b coefficient. The Mann-Whitney U-test was used to compare dislocation resistance
      between groups 1 and 2 and fluid transport between groups 1 and 3. Significance
      level was set at P < 0.05. RESULTS: Kendall's tau-b correlation coefficients
      between fluid transport and dislocation resistance were weak, being coronally
      0.139 (P = 0.444) and apically -0.080 (P = 0.658). No significant difference in
      dislocation resistance could be detected between groups 1 and 2 at both root
      levels (P = 0.052 and P = 0.336, respectively). CONCLUSION: No significant
      correlation could be identified between fluid transport and dislocation
      resistance, meaning that the corono-apical sealing ability of a methacrylate
      based root canal filling is independent of its adhesive properties as indicated
      by its dislocation resistance.

PMID- 24749657
TI  - Help break the stigma against mental illness!

PMID- 24749658
TI  - First report of ipilimumab-induced Grover disease.

PMID- 24749659
TI  - The utility of the PCR melting profile technique for typing Corynebacterium
      diphtheriae isolates.
AB  - Selection of appropriate typing method depends on a number of factors, including
      the scale of the investigation, the rapidity required of the results and the
      financial and technical resources available. Several typing methods have been
      applied to Corynebacterium diphtheriae genotyping, but most are laborious and
      time-consuming or require expensive equipment. We report an evaluation of the
      utility of the PCR melting profile technique for simple and easy-to-perform
      genotyping of C. diphtheriae. We compared the method with ribotyping-the 'gold
      standard' for C. diphtheriae typing-and PFGE, MLST, AFLP, RAPD and spoligotyping.
      SIGNIFICANCE AND IMPACT OF THE STUDY: Occurrence of Corynebacterium diphtheriae
      infections-in the form of diphtheria in endemic countries and in the form of
      invasive infections in countries with high antidiphtheria vaccination coverage
      indicates the need for maintenance of ability to genotype this pathogen by
      laboratories. Application of an appropriate typing method is essential not only
      in outbreak investigations for understanding and predicting epidemics but also in
      monitoring of the evolution and spread of epidemic clones of C. diphtheriae. The
      PCR melting profile method presented in the study is a good alternative for C.
      diphtheriae typing.

PMID- 24749660
TI  - Uricaemia and ejection fraction in elderly heart failure outpatients.
AB  - BACKGROUND: Preliminary data suggest that serum uric acid (SUA) could be involved
      in the prognosis of chronic heart failure (HF). The aim of our study was to test
      the relationship between SUA and left ventricular ejection fraction (EF%) in a
      cohort of elderly hypertensive outpatients with chronic HF. DESIGN: We
      consecutively enrolled 487 elderly outpatients (M = 59.8%; F = 40.2%; mean age:
      72 +/- 11 years old) affected by mild-to-moderate hypertensive and/or ischaemic
      HF, evaluating the relationship between SUA and EF%. RESULTS: In an univariate
      analysis, SUA was inversely related with EF%: B = -4.392, 95% CI -5.427 to 
      3.357, P < 0.001. After adjustment for a large number of variables in a
      multivariate analysis, the value of EF% was best predicted by SUA (B = -3.005,
      95% CI -4.386 to -1.623, P < 0.001), log brain natriuretic peptide (BNP: B = 
      2.341, 95% CI -3.137 to -1.248, P < 0.001) and mean arterial pressure (MAP: B =
      0.241, 95% CI 0.047 to 0.435, P = 0.015). A separate analysis by estimated
      glomerular filtration rate (eGFR) levels confirmed the inverse relationship
      between SUA and EF% in patients with normal renal function. A separate analysis
      by sex confirmed that SUA and log BNP were significant strong predictors of EF%
      in men, but not in women where the best predictors were log BNP, MAP and body
      mass index. The predicting role of SUA was apparently independent of eGFR and use
      of diuretics. CONCLUSION: Serum uric acid seems to be inversely related to EF% in
      male elderly patients with HF after adjustment for the several confounding
      factors. This observation supports a primary negative effect of SUA on left
      ventricular function that warrants further investigations.

PMID- 24749661
TI  - Sun exposure and protection behavior of Danish farm children: parental influence
      on their children.
AB  - Healthy sun habits acquired in childhood could reduce skin cancer incidence. We
      examined the sun exposure and protection behavior of an expected high-exposure
      group of children, and the association to their parents. Open, prospective cohort
      study. One hundred and thirty nine participants (40 families) kept daily sun
      behavior diaries (sun exposure, sunscreen use, sunburns) over a 4-month summer
      period (15,985 diary days). The Pigment Protection Factor (PPF), an objective
      measure of sun exposure, was measured at two body sites, before and after summer.
      All participants presented data from the same 115 days. Risk behavior (sun
      exposure of upper body) took place on 9.5 days (boys) and 15.6 days (girls).
      Sunburn and sunscreen use were infrequent. Boys' sun exposure resulted in an
      increased photo protection over the study period of 1.7 SED (upper arm) and 0.8
      SED (shoulder) to elicit erythema. Corresponding values for girls were as
      follows: 0.9 SED (upper arm) and 0.5 SED (shoulder). Boys' sunscreen use
      correlated to their mothers' (r = 0.523, P = 0.02). Girls' number of risk days (r
      = 0.552, P = 0.005) and sun exposure (upper arm: r = 0.621, P < 0.001) correlated
      to their mothers'. The children's sun exposure was substantial. Only mothers
      influenced children's sun behavior and exposure. This may be of relevance in
      future sun protection campaigns.

PMID- 24749662
TI  - Identification and quantification of neuropeptides in naive mouse spinal cord
      using mass spectrometry reveals [des-Ser1]-cerebellin as a novel modulator of
      nociception.
AB  - Neuropeptide transmitters involved in nociceptive processes are more likely to be
      expressed in the dorsal than the ventral horn of the spinal cord. This study was
      designed to examine the relative distribution of neuropeptides between the dorsal
      and ventral spinal cord in naive mice using liquid chromatography, high
      resolution mass spectrometry. We identified and relatively quantified 36 well
      characterized full-length neuropeptides and an additional 168 not previously
      characterized peptides. By extraction with organic solvents we identified seven
      additional full-length neuropeptides. The peptide [des-Ser1]-cerebellin (desCER),
      originating from cerebellin precursor protein 1 (CBLN1), was predominantly
      expressed in the dorsal horn. Immunohistochemistry showed the presence of CBLN1
      immunoreactivity with a punctate cytoplasmic pattern in neuronal cell bodies
      throughout the spinal gray matter. The signal was stronger in the dorsal compared
      to the ventral horn, with most CBLN1 positive cells present in outer laminae
      II/III, colocalizing with calbindin, a marker for excitatory interneurons.
      Intrathecal injection of desCER induced a dose-dependent mechanical
      hypersensitivity but not heat or cold hypersensitivity. This study provides
      evidence for involvement of desCER in nociception and provides a platform for
      continued exploration of involvement of novel neuropeptides in the regulation of
      nociceptive transmission. Neuropeptides involved in nociceptive processes are
      more likely to be expressed in the dorsal than the ventral horn of spinal cord.
      Well-characterized full-length neuropeptides as well as uncharacterized
      neuropeptides were quantified by mass spectrometry. The CBLN1-derived peptide
      [des-Ser1]-cerebellin (desCER) is predominantly expressed in the dorsal horn, and
      intrathecal injection of desCER induced a dose-dependent mechanical
      hypersensitivity. 

PMID- 24749663
TI  - Microwave-assisted synthesis of diverse pyrrolo[3,4-c]quinoline-1,3-diones and
      their antibacterial activities.
AB  - With the aim of developing a general and practical method for library production,
      a novel and efficient two-phase microwave-assisted cascade reaction between
      isatins and beta-ketoamides in [Bmim]BF4/toluene was developed for the synthesis
      of pyrrolo[3,4-c]quinoline-1,3-diones. The features of this methodology are, the
      use of microwave-assisted rapid synthesis, mild reaction conditions, high yields,
      operational simplicity, facile product separation, and recyclability.
      Furthermore, the antibacterial activities of the pyrrolo[3,4-c]quinoline-1,3
      dione derivatives produced were evaluated against Gram-negative bacteria
      (Escherichia coli, Pseudomonas aeruginosa, and Enterobacter aerogenes) and Gram
      positive bacteria (Bacillus cereus and Staphylococcus aureus). These derivatives
      showed antibacterial activities against Gram-positive strains that were at least
      equivalent to that against Gram-negative strains. Compound 7{3,5} displayed the
      most potent antibacterial activity against P. aeruginosa (MIC = 0.5 MUg/mL) and
      greater activity than standard ampicillin (MIC = 1 MUg/mL). Compound 7{4,7}
      exhibited the best inhibitory activity against E. coli and E. aerogenes (MIC = 1
      and 0.5 MUg/mL), compared with the standard ampicillin (both MICs = 1 MUg/mL).
      The synthesized pyrrolo[3,4-c]quinoline-1,3-diones are expected to be widely used
      as lead compounds for the development of new antibacterial agents. 

PMID- 24749664
TI  - A randomized controlled trial evaluating the effects of online rehabilitative
      intervention for adult hearing-aid users.
AB  - OBJECTIVE: Previous research shows that the internet can be used in the
      rehabilitation of hearing-aid users. By further developing the online program, it
      might be possible to foster behavioral changes that will positively affect
      hearing-aid users. DESIGN: A randomized controlled study with two groups of
      participants. The intervention group underwent a five-week online intervention
      while the control group was referred to a waiting list. Questionnaires were used
      as outcome measures. STUDY SAMPLE: Seventy-six experienced hearing-aid users
      participated in the study, ranging in age from 26 to 81 years (mean 69.3 years).
      RESULTS: The findings showed significant improvements in the intervention group
      after the intervention, measured by the hearing handicap inventory for the
      elderly. The effects were maintained and improved at the follow-up. Furthermore,
      the results indicated that the participants in the intervention group improved at
      two items of the international outcome inventory for hearing aids, and the
      effects were partly maintained at the follow-up. Finally, significant
      improvements in the domain of psychosocial wellbeing were found at the follow-up.
      CONCLUSIONS: This study provides further evidence that the internet can be used
      to deliver intervention of rehabilitation to hearing-aid users.

PMID- 24749665
TI  - Extended high-frequency (9-20 kHz) audiometry reference thresholds in 645 healthy
      subjects.
AB  - OBJECTIVE: The aim of the present study was to study patterns in the extended
      spectrum of the human hearing (0.125 to 20 kHz) in order to obtain reference
      thresholds. Then, we compare our values with existing results at extended high
      frequencies (8 to 20 kHz) in an attempt to establish new standards for potential
      international adoption. DESIGN: A prospective study in a group of otologically
      healthy subjects. STUDY SAMPLE: A total of 645 subjects aged between 5 and 90
      years were recruited. Pure-tone thresholds were determined for conventional and
      extended high-frequencies. RESULTS: There was an increase in the hearing
      thresholds as a function of frequency and age. For the 20 to 69 years old group,
      thresholds were lower in females than in males, especially at 12.5 and 16 kHz.
      Our threshold values are comparable to those presented in previous studies that
      used different instrumentation and populations. CONCLUSIONS: When comparing
      different studies the hearing thresholds were found to be similar. Therefore, it
      would be possible to establish international standard thresholds.

PMID- 24749666
TI  - A critical review of which children with acute myeloid leukaemia need stem cell
      procedures.
AB  - The last decades have seen parallel improvements in chemotherapy-based and
      haematopoietic stem cell transplantation (HSCT) regimens for acute myeloid
      leukaemia (AML) in children. There has been no consensus on indication for HSCT.
      Reserving HSCT for high-risk and relapsed patients spare many patients from the
      long-term toxicity of this treatment. The results of matched unrelated donor HSCT
      equal family donor transplantation and the presence of a matched sibling should
      no longer be a transplant indication. Minimal residual disease measured by flow
      cytometry may identify poor responders benefitting from HSCT in first complete
      remission (CR1) and those with a favourable response to induction therapy who do
      not need HSCT even with adverse cytogenetic aberrations. FLT3-internal tandem
      duplication without NPM1 mutation has a very high relapse rate despite favourable
      response and HSCT is indicated in CR1 in these cases. Finding the optimal
      indications for HSCT is a delicate balance between risk of relapse and late
      effects. 

PMID- 24749667
TI  - Exotic birds increase generalization and compensate for native bird decline in
      plant-frugivore assemblages.
AB  - Exotic species are thought to alter the structure of natural communities and
      disrupt ecosystem functioning through invasion. Nevertheless, exotic species may
      also provide ecological insurance when they contribute to maintain ecosystem
      functions after the decline of native species following anthropogenic
      disturbance. Here, this hypothesis is tested with the assemblage of frugivorous
      birds and fleshy-fruited plants of New Zealand, which has suffered strong
      historical declines in native birds while simultaneously gaining new frugivores
      introduced by European settlers. We studied the plant-frugivore assemblage from
      measures of fruit and bird abundances and fruit consumption in nine forest
      patches, and tested how this changed across a gradient of relative abundance of
      exotic birds. We then examined how each bird species' role in the assemblage (the
      proportion of fruits and the number of plant species consumed) varied with their
      relative abundance, body size and native/exotic status. The more abundant and, to
      a lesser extent, larger birds species consumed a higher proportion of fruits from
      more plant species. Exotic birds consumed fruits less selectively and more
      proportionate to the local availability than did native species. Interaction
      networks in which exotic birds had a stronger role as frugivores had higher
      generalization, higher nestedness and higher redundancy of plants. Exotic birds
      maintained frugivory when native birds became rarer, and diversified the local
      spectrum of frugivores for co-occurring native plants. These effects seemed
      related to the fact that species abundances, rather than trait-matching
      constraints, ultimately determined the patterns of interactions between birds and
      plants. By altering the structure of plant-frugivore assemblages, exotic birds
      likely enhance the stability of the community-wide seed dispersal in the face of
      continued anthropogenic impact. 

PMID- 24749668
TI  - Pulse-waveform analysis of normal population using laser speckle flowgraphy.
AB  - PURPOSE: Laser speckle flowgraphy (LSFG), a new, non-invasive method of measuring
      the mean blur rate (MBR) of ocular blood flow, allows for the analysis of the
      pulse waveform of a heartbeat as it changes dynamically. Here, we investigated
      the relationship between the pulse waveform and clinical parameters, particularly
      age. MATERIALS AND METHODS: Sixty eyes of 60 healthy subjects without diabetes
      were enrolled from among patients undergoing annual health examinations. LSFG,
      and its analysis software, were used to determine pulse waveform parameters
      including MBR, skew, blowout score (BOS), blowout time (BOT), rising rate and
      falling rate in the optic nerve head (ONH), both specifically in the tissue area
      and in the ONH overall. Fifteen clinical parameters were also recorded, including
      age and blood pressure, as well as triglyceride and creatinine levels. RESULTS:
      Skew, BOT and falling rate had a strong correlation (|r| > 0.60) with age, but
      not with the other clinical parameters. This correlation with age was stronger in
      the tissue area (BOT: p < 0.0001, r = - 0.68; skew: p < 0.0001, r = 0.65; falling
      rate: p < 0.0001, r = 0.61) than in the ONH overall (BOT: p < 0.0001, r = -0.67;
      skew: p < 0.0001, r = 0.60; falling rate: p < 0.0001, r = 0.59). Stepwise
      multiple regression analysis revealed that tissue area falling rate was an
      independent factor indicating age, and conversely that age was an independent
      factor indicating tissue area falling rate. CONCLUSIONS: The significant
      correlation of LSFG-measured tissue area falling rate with age suggests that it
      may be a new candidate biomarker for age-dependent microcirculation.

PMID- 24749669
TI  - Multi-dimensional separations of polymers.
AB  - Synthetic polymers and comprehensive two-dimensional liquid chromatography (LC *
      LC) are a synergistic combination. LC * LC provides unique insights in mutually
      dependent molecular distributions. Synthetic polymers offer clear demonstrations
      of the value of LC * LC. 

PMID- 24749670
TI  - The comparison of DPPH-scavenging capacity and anti-inflammatory effects of
      phenolic compounds isolated from the stems of Stewartia koreana Nakai.
AB  - The Stewartia koreana Nakai (SK) had been used in oriental traditional medicine
      as a remedy for acute gastroenteritis, liver diseases, quadriplegia and pain. The
      antioxidant activity guided isolation 80% methyl extract from stems of SK yielded
      eight phenolic compounds. We evaluated the anti-oxidative and anti-inflammatory
      effects of these compounds via assays of 1,1-diphenyl-2-picrylhydazyl (DPPH)
      radicals and inhibition of nitric oxide (NO) production in lipopolysaccharide
      stimulated RAW 264.7 macrophage cells. The results demonstrated that
      syringaresinol (6) exhibited significant DPPH radical-scavenging activity and
      inhibitory effects on NO production compared with its positive controls, ascorbic
      acid and L-NMMA, respectively.

PMID- 24749671
TI  - Longer hospitalization of patients with positive blood cultures receiving total
      parenteral nutrition.
AB  - BACKGROUND: Total parenteral nutrition (TPN) via central venous catheters has
      improved nutrient delivery to patients unable to receive nutrition enterally, but
      its administration can be complicated by bacteremia and fungemia. METHODS: At a
      large tertiary-care academic medical center, 245 patients with concurrent
      positive blood cultures, among 1,716 adult patients who received TPN over a
      period of three consecutive years, were divided into those in whom parenteral
      nutrition was continued and those in whom it was stopped after the occurrence of
      a positive blood culture. To determine whether continuation of TPN after a
      positive blood culture was associated with a statistically significantly longer
      hospitalization than with its discontinuation after a positive blood culture, we
      performed a logistic regression analysis with step-wise selection, with
      parenteral nutrition status as the dependent variable and type of venous access,
      type of pathogen responsible for a positive blood culture, recurrence of a
      positive blood culture, respiratory failure, shock, and length of stay as
      covariates. RESULTS: The prevalence of positive blood cultures was 14% among all
      hospitalized patients given parenteral nutrition. Parenteral nutrition was
      continued in 60% of the patients. Baseline co-morbid and laboratory parameters
      were comparable in the group of patients in whom TPN was continued and the group
      in which it was stopped except that the white blood cell count (WBC) was lower in
      the former group (9.1+/-6.6 mm(3) vs. 12+/-12.1 mm(3), p=0.015). Both groups
      received an average of 30 kcal/kg and 1.4 g protein/kg via TPN. There was no
      difference in the two groups in total calories, lipids, protein, or glutamine
      base received before the occurrence of a positive blood culture (p=0.86, p=0.51,
      p=0.79, and p=0.42, respectively). The hospital stay of the group in which TPN
      was continued after a positive blood culture was statistically significantly
      longer than that of the group in which it was discontinued (44.6+/-32.3 d vs.
      28.2+/-18.5 d, p<0.001). This difference remained significant in the
      multivariable logistic regression analysis. CONCLUSION: Continuation of TPN after
      a positive blood culture was associated with statistically significantly longer
      hospitalization before and after adjustment for co-morbid conditions.

PMID- 24749673
TI  - Theoretical kinetics study of the O(3P) + CH4/CD4 hydrogen abstraction reaction:
      the role of anharmonicity, recrossing effects, and quantum mechanical tunneling.
AB  - Using a recently developed full-dimensional accurate analytical potential energy
      surface [Gonzalez-Lavado, E., Corchado, J. C., and Espinosa-Garcia, J. J. Chem.
      Phys. 2014, 140, 064310], we investigate the thermal rate coefficients of the
      O((3)P) + CH4/CD4 reactions with ring polymer molecular dynamics (RPMD) and with
      variational transition-state theory with multidimensional tunneling corrections
      (VTST/MT). The results of the present calculations are compared with available
      experimental data for a wide temperature range 200-2500 K. In the classical high
      temperature limit, the RPMD results match perfectly the experimental data,
      whereas VTST results are smaller by a factor of 2. We suggest that this
      discrepancy is due to the harmonic approximation used in the present VTST
      calculations, which leads to an overestimation of the variational effects. At low
      temperatures the tunneling plays an important role, which is captured by both
      methods, although they both overestimate the experimental values. The analysis of
      the kinetic isotope effects shows a discrepancy between both approaches, with the
      VTST values smaller by a factor about 2 at very low temperatures. Unfortunately,
      no experimental results are available to shed any light on this comparison, which
      keeps it as an open question.

PMID- 24749672
TI  - Investigational FMS-like tyrosine kinase 3 inhibitors in treatment of acute
      myeloid leukemia.
AB  - INTRODUCTION: Outcomes for the majority of patients with acute myeloid leukemia
      (AML) remain poor. Over the past decade, significant progress has been made in
      the understanding of the cytogenetic and molecular determinants of AML
      pathogenesis. One such advance is the identification of recurring mutations in
      the FMS-like tyrosine kinase 3 gene (FLT3). Currently, this marker, which appears
      in approximately one-third of all AML patients, not only signifies a poorer
      prognosis but also identifies an important target for therapy. FLT3 inhibitors
      have now undergone clinical evaluation in Phase I, II and III clinical trials, as
      both single agents and in combination with chemotherapeutics. Unfortunately, to
      date, none of the FLT3 inhibitors have gained FDA approval for the treatment of
      patients with AML. Yet, several promising FLT3 inhibitors are being evaluated in
      all phases of drug development. AREAS COVERED: This review aims to highlight the
      agents furthest along in their development. It also focuses on those FLT3
      inhibitors that are being evaluated in combination with other anti-leukemia
      agents. EXPERT OPINION: The authors believe that the field of research for FLT3
      inhibitors remains promising, despite the historically poor prognosis of this
      subgroup of patients with AML. The most promising areas of research will likely
      be the elucidation of the mechanisms of resistance to FLT3 inhibitors, and
      development of potent FLT3 inhibitors alone or in combination with
      hypomethylating agents, cytotoxic chemotherapy or with other targeted agents.

PMID- 24749675
TI  - Gomisin A decreases the LPS-induced expression of iNOS and COX-2 and activation
      of RIP2/NF-kappaB in mouse peritoneal macrophages.
AB  - Gomisin A (GA), a lignan component contained in the fruit of Schisandra chinensis
      Baillon, improves hepatic cell degeneration, vasodilatory activity and insulin
      sensitivity. These effects also impact the immune system, including various
      inflammatory mediators and cytokines. In this study, the anti-inflammatory effect
      of GA on lipopolysaccharide-stimulated mouse peritoneal macrophages was studied.
      Pretreatment with GA attenuated the expression of receptor-interacting protein 2
      (RIP2) and IkappaB kinase-beta (IKK-beta) as well as IKK-beta phosphorylation.
      The activation of nuclear factor-kappa B (NF-kappaB) in the nucleus, the
      phosphorylation of IkappaBalpha and degradation of IkappaBalpha in the cytosol
      were suppressed by GA. GA decreased the production and mRNA expression of the
      inflammatory cytokines tumor necrosis factor-alpha (TNF-alpha) and interleukin
      (IL)-6. In addition, expression of inducible nitric oxide synthase (iNOS) and
      cyclooxygenase-2 (COX-2) and production of nitric oxide were decreased by
      pretreatment with GA. In conclusion, these results show that the anti
      inflammatory properties of GA potentially result from the inhibition of COX-2,
      iNOS, IL-6, TNF-alpha and NO through the down-regulation of RIP2 and NF-kappaB
      activation. These results impact the development of potential health products for
      preventing and treating inflammatory diseases.

PMID- 24749676
TI  - The distinction of 'psychosomatogenic family types' based on parents' self
      reported questionnaire information: a cluster analysis.
AB  - The theory of 'psychosomatogenic family types' is often used in treatment of
      somatizing adolescents. This study investigated the validity of distinguishing
      'psychosomatogenic family types' based on parents' self-reported family features.
      The study included a Flemish general population sample of 12-year olds (n =
      1428). We performed cluster analysis on 3 variables concerning parents' self
      reported problems in family functioning. The distinguished clusters were examined
      for differences in marital problems, parental emotional problems, professional
      help for family members, demographics, and adolescents' somatization. Results
      showed the existence of 5 family types: 'chaotic family functioning,' 'average
      amount of family functioning problems,' 'few family functioning problems,' 'high
      amount of support and communication problems,' and 'high amount of sense of
      security problems' clusters. Membership of the 'chaotic family functioning' and
      'average amount of family functioning problems' cluster was significantly
      associated with higher levels of somatization, compared with 'few family
      functioning problems' cluster membership. Among additional variables, only
      marital and parental emotional problems distinguished somatization relevant from
      non relevant clusters: parents in 'average amount of family functioning problems'
      and 'chaotic family functioning' clusters reported higher problems. The data
      showed that 'apparently perfect' or 'enmeshed' patterns of family functioning may
      not be assessed by means of parent report as adopted in this study. In addition,
      not only adolescents from 'extreme' types of family functioning may suffer from
      somatization. Further, professionals should be careful assuming that families in
      which parents report average to high amounts of family functioning problems also
      show different demographic characteristics.

PMID- 24749674
TI  - Alveolar macrophages contribute to the pathogenesis of human metapneumovirus
      infection while protecting against respiratory syncytial virus infection.
AB  - Human metapneumovirus (hMPV) and respiratory syncytial virus (RSV) are leading
      causes of upper and lower respiratory tract infections in young children and
      among elderly and immunocompromised patients. The pathogenesis of hMPV-induced
      lung disease is poorly understood. The lung macrophage population consists of
      alveolar macrophages (AMs) residing at the luminal surface of alveoli and
      interstitial macrophages present within the parenchymal lung interstitium. The
      involvement of AMs in innate immune responses to virus infections remains
      elusive. In this study, BALB/c mice depleted of AMs by intranasal instillation of
      dichloromethylene bisphosphonate (L-CL2MBP) liposomes were examined for disease,
      lung inflammation, and viral replication after infection with hMPV or RSV. hMPV
      infected mice lacking AMs exhibited improved disease in terms of body weight
      loss, lung inflammation, airway obstruction, and hyperresponsiveness compared
      with AM-competent mice. AM depletion was associated with significantly reduced
      hMPV titers in the lungs, suggesting that hMPV required AMs for early entry and
      replication in the lung. In contrast, AM depletion in the context of RSV
      infection was characterized by an increase in viral replication, worsened
      disease, and inflammation, with increased airway neutrophils and inflammatory
      dendritic cells. Overall, lack of AMs resulted in a broad-spectrum disruption in
      type I IFN and certain inflammatory cytokine production, including TNF and IL-6,
      while causing a virus-specific alteration in the profile of several
      immunomodulatory cytokines, chemokines, and growth factors. Our study
      demonstrates that AMs have distinct roles in the context of human infections
      caused by members of the Paramyxoviridae family.

PMID- 24749677
TI  - The transition of health care responsibility from parents to youth diagnosed with
      chronic illness: a developmental systems perspective.
AB  - With improved health care, increasing numbers of children and adolescents with
      chronic illness and disability now live into adulthood. With this change, the
      health care community needs to address problems related to the transition from
      parents caring for their young children's needs to increasing health care
      responsibility being required of adolescents and young adults (AYA). The current
      article presents a conceptualization of relevant research related to the
      transition of health care responsibility from parent to AYA. Using a
      developmental systems perspective, representative literature on adolescent and
      dyad-level factors related to the transition of health care responsibility is
      reviewed to inform clinical practice and future intervention research. To
      identify the health care tasks that researchers have thus far considered as most
      important for successful transition, we review assessment measures in this area.
      The varying levels of agreement on transition of health care behaviors provide an
      index of current thought by experts in this field. Those behaviors consistently
      identified as key for successful transition of responsibility from parent to
      adolescent are outlined to inform future research and clinical practice.

PMID- 24749678
TI  - A permanent emergency: a longitudinal study on families coping with amyotrophic
      lateral sclerosis.
AB  - Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that has a
      strong impact on the lives of the people affected and on their close relatives,
      who have to tackle the demanding duties of caring for and assisting them. Family
      life can be profoundly influenced by this disease, and evaluating how the
      relevant parameters of family functioning relate to the markers of psychological
      adjustment of patients and caregivers is an important research objective, with
      implications for clinical practice. We examined the associations of family
      cohesion and adaptability (FACES III) with patients' coping strategies (MND
      Coping Scale) and caregivers' burden (CBI) in a longitudinal study with a sample
      of 19 pairs of patients with ALS and primary caregivers. The results showed a
      tendency toward patterns of extreme family functioning, with increasing levels of
      cohesion and adaptability, especially in the ideal versions of family
      functioning. Such high levels of cohesion and adaptability were correlated with
      positive markers of adjustment, especially in terms of the adaptive coping
      strategies of patients. Increasing and extreme levels of both cohesion and
      adaptability seem to be expected and even adaptive in the case of a progressive
      and impairing disease like ALS. Methodological concerns regarding the
      operationalization of family functioning constructs are also discussed.

PMID- 24749679
TI  - Including the family in research evaluating integrated care: a call for expanding
      investigators' scope beyond single-person measures.
AB  - As providers across the fields of behavioral- and biomedical- care advance
      efforts to include patients' families in the care that they provide, we must also
      include families in the research that we conduct. Additional knowledge about
      families in treatment could help us screen families at risk for poor outcomes,
      design more appropriate family based interventions, and more completely assess
      the impact(s) of interventions on both patients and their families. In this
      account, we outline assessments that are useful in responding to this call. We
      consider tools that target general family functioning, that are sensitive to
      change and progress, and that are adaptable to common time- and administrative-
      constraints within medical settings. We highlight strengths and weaknesses within
      the pool of measures that are currently available, and offer suggestions and next
      steps in instrument-design and development.

PMID- 24749680
TI  - Health and well-being in midlife parents of children with special health needs.
AB  - The objectives of this study were to delineate variation in mental and physical
      health outcomes over a 10-year period among parents with a child with special
      health needs as compared to parents of a typically developing child; and evaluate
      the possible protective effects of parental perceived control and social support.
      The sample consisted of 646 parents from the longitudinal Midlife Development in
      the United States (MIDUS) study. Nearly one-quarter of the sample (n = 128;
      22.3%) reported having a child with a special health care need. Cross-sectional
      analyses indicated that parents of a child with special care needs reported
      poorer self-rated mental health, greater depressive symptoms, and more
      restrictions in instrumental activities of daily living (IADL). Parents of a
      child with special health care needs had greater increases in depressive symptoms
      over time and greater declines in instrumental activities of daily living than
      parents of typically developing children. Perceived control was a robust
      predictor of all health outcomes over time. The added stressors of parenting a
      child with special health needs may undermine the long-term health of parents.
      Behavioral interventions and clinical practices that facilitate parental
      perceived control may enable resilience and better health.

PMID- 24749682
TI  - Does verbal encouragement actually improve performance in the 6-minute walk test?
AB  - The purpose of this study was to evaluate the performance in the 6-minute walk
      test (6 MWT) of elderly patients with chronic obstructive pulmonary disease
      (COPD) by comparing to a group of healthy elderly patients, performed with and
      without verbal encouragement. This cross-sectional study compared 40 patients
      with COPD (forced expiratory volume in the first second (FEV1%) = 53.7 +/- 23.8%;
      forced vital capacity (FVC%) = 65.5 +/- 20.8%; and the FEV1/FVC ratio = 55.4 +/-
      12.4) and 40 healthy elderly patients (control). The 6 MWT's were performed with
      and without verbal encouragement according to the American Thoracic Society
      (ATS), monitoring the distance walked (6 MWD), the duration of walking (TW) and
      the perceived effort index (PEI) through the Borg scale between the groups. No
      differences were observed in patients with COPD when the tests were performed
      with and without verbal encouragement for the 6 MWD, TW and PEI, the same
      occurring in the control group for the 6 MWD, TW and PEI, respectively. The use
      of verbal encouragement was not sufficient to promote improvement in the
      performance of the 6 MWT (6 MWD, TW and PEI) of patients with COPD and healthy
      elderly patients.

PMID- 24749683
TI  - Effects of oleic acid on the corneal permeability of compounds and evaluation of
      its ocular irritation of rabbit eyes.
AB  - OBJECTIVE: To explore the use of oleic acid (OA) in ocular drug delivery.
      METHODS: Six compounds, namely rhodamine B, sodium-fluorescein, fluorescein
      isothiocyanate (FITC) dextrans of 4, 10, 20 and 40 kDa were selected as model
      drugs. The effect of OA on the corneal permeability of drugs was evaluated in
      vitro, using isolated rabbit corneas by a Franz diffusion cell. The safety of OA
      was assessed on the basis of corneal hydration level. The ocular irritation of OA
      was also tested in rabbits in vivo using the Draize eye test. RESULTS: In the
      presence of OA, at a concentration of 0.02-0.1%, the maximum increase in the
      apparent permeability coefficient (Papp) was 3.21-, 1.76- and 1.57-fold for
      rhodamine B, sodium-fluorescein and FITC-dextran of 4 kDa, respectively. However,
      no significant permeability enhancement of FITC-dextrans of 4, 10, 20 and 40 kDa
      was found in the presence of OA. It enhanced the corneal penetration of model
      compounds in a concentration-dependent manner. The Papp values of rhodamine B
      decreased with increasing concentration of OA, while the Papp values of sodium
      fluorescein and FITC-dextrans of 4 kDa increased. The Papp enhanced by 0.1% OA
      was logarithmically correlated to the molecular weight of model drugs (R(2) =
      0.9991). With the 0.02%, 0.05% and 0.1% oleic application, the corneal hydration
      values were <83%, and Draize scores were <4. CONCLUSION: OA may have potential
      clinical benefits in improving the ocular drug delivery of both hydrophilic and
      lipophilic compounds.

PMID- 24749684
TI  - Abundance, diversity and seasonal dynamics of predatory bacteria in aquaculture
      zero discharge systems.
AB  - Standard aquaculture generates large-scale pollution and strains water resources.
      In aquaculture using zero discharge systems (ZDS), highly efficient fish growth
      and water recycling are combined. The wastewater stream is directed through
      compartments in which beneficial microbial activities induced by creating
      suitable environmental conditions remove biological and chemical pollutants,
      alleviating both problems. Bacterial predators, preying on bacterial populations
      in the ZDS, may affect their diversity, composition and functional redundancy,
      yet in-depth understanding of this phenomenon is lacking. The dynamics of
      populations belonging to the obligate predators Bdellovibrio and like organisms
      (BALOs) were analyzed in freshwater and saline ZDS over a 7-month period using
      QPCR targeting the Bdellovibrionaceae, and the Bacteriovorax and Bacteriolyticum
      genera in the Bacteriovoracaeae. Both families co-existed in ZDS compartments,
      constituting 0.13-1.4% of total Bacteria. Relative predator abundance varied
      according to the environmental conditions prevailing in different compartments,
      most notably salinity. Strikingly, the Bdellovibrionaceae, hitherto only
      retrieved from freshwater and soil, also populated the saline system. In addition
      to the detected BALOs, other potential predators were highly abundant, especially
      from the Myxococcales. Among the general bacterial population, Flavobacteria,
      Bacteroidetes, Fusobacteriaceae and unclassified Bacteria dominated a well mixed
      but seasonally fluctuating diverse community of up to 238 operational taxonomic
      units, as revealed by 16S rRNA gene sequencing. 

PMID- 24749685
TI  - Kidney biopsy results versus clinical parameters on mortality and ESRD
      progression in 2687 patients with glomerulonephritis.
AB  - BACKGROUND: Physicians refer proteinuric patients to kidney biopsy in order to
      clarify the issue of underlying renal disease. We compared kidney biopsy results
      with classical outcome parameters in a large cohort of patients with biopsy
      proven glomerulonephritis (GN). METHODS: In a retrospective analysis, 2687
      patients with different forms of GN from 123 Austrian centres were investigated.
      Patient characteristics, the diagnosis of GN and its respective subtype and
      clinical symptoms such as arterial hypertension, haematuria, amount of
      proteinuria and estimated glomerular filtration rate (eGFR) were tested for their
      association with all-cause mortality and progression to end-stage renal disease
      (ESRD). RESULTS: During a median follow-up of 129.9 months (IQR 89.6; 177.7), 688
      patients (25.6%) died and 718 patients required dialysis (29.4%). In multivariate
      Cox's regression analysis age (HR 1.06), female sex (HR 0.71), eGFR (HR 0.74),
      the diagnosis of GN and its subtypes predicted patient survival (all P < 0.01),
      whereas the amount of proteinuria was not associated with patient survival. The
      incidence of progression to ESRD was associated with female sex (HR 0.71), eGFR
      (HR 0.65), amount of proteinuria (HR 1.15) and the diagnosis of GN and its
      subtypes (all P < 0.01). Nephrotic or nephritic syndromes were not associated
      with patient survival or progression to ESRD and did not add further predictive
      value to outcome of GN. CONCLUSIONS: Our study demonstrates histological
      diagnosis of GN and its specific subtype predicts patient survival and dialysis
      incidence. Therefore, kidney biopsy should be an integral part of routine
      diagnostic assessment in patients with any forms of suspected GN.

PMID- 24749686
TI  - Biotyping of cultivable lactic acid bacteria isolated from donkey milk.
AB  - The diversity of lactic acid bacteria (LAB) species in donkey's milk was analysed
      by culture-dependent microbial techniques. Dominant strains were isolated on agar
      media generally used for enumerating LAB. To enrich the number of acidifying LAB
      present, the milk samples were incubated at 37 degrees C for 24 h (cultured milk
      samples, CM). One of the CM samples was heat-treated at 63 degrees C for 10 min
      before incubation at 37 degrees C (heat-treated and cultured milk sample, TCM) to
      select thermophilic LAB. The microflora in these CM and TCM samples was then
      compared to that of the raw milk samples (RM). Among the 129 LAB isolates, 10
      different species (four Enterococcus, five Streptococcus and one Pediococcus)
      were identified by molecular methods. Although the 10 LAB species were present in
      the RM samples, only three and two isolates were found in CM and TCM samples,
      respectively. Despite the selection protocol being set up to favour the isolation
      of all LAB isolates present in donkey milk, relatively few species and biotypes
      were isolated. No LAB isolates belonging to the most technologically important
      dairy starter species were detected. The possible factors related to the limited
      LAB diversity in donkey's milk have been discussed below. SIGNIFICANCE AND IMPACT
      OF THE STUDY: There is increased interest in using donkey's milk as a source of
      human nutrition. The large amounts of antimicrobial components and defence
      factors present in donkey's milk provide protection from microbial infections and
      distinguish donkey's milk from the milks of other mammals. However, the
      microbiota in donkey's milk has so far been poorly characterized, specifically
      with regard to the lactic acid bacteria (LAB). This study has identified
      cultivable, acidifying and thermoduric LAB that could be used to develop starter
      cultures. This is the first study to investigate the culturable LAB microbiota
      present in donkey's milk.

PMID- 24749687
TI  - Activation of the aryl hydrocarbon receptor affects activation and function of
      human monocyte-derived dendritic cells.
AB  - Aryl hydrocarbon receptor (AhR) is well known for mediating the toxic effects of
      dioxin-containing pollutants, but has also been shown to be involved in the
      natural regulation of the immune response. In this study, we investigated the
      effect of AhR activation by its endogenous ligands 6-formylindolo[3,2-b]carbazole
      (FICZ) and 2-(1'H-indole-3'-carbonyl)-thiazole-4-carboxylic acid methyl ester
      (ITE) on the differentiation, maturation and function of monocyte-derived DCs in
      Behcet's disease (BD) patients. In this study, we showed that AhR activation by
      FICZ and ITE down-regulated the expression of co-stimulatory molecules including
      human leucocyte antigen D-related (HLA-DR), CD80 and CD86, while it had no effect
      on the expression of CD83 and CD40 on DCs derived from BD patients and normal
      controls. Lipopolysaccharide (LPS)-treated dendritic cells (DCs) from active BD
      patients showed a higher level of interleukin (IL)-1beta, IL-6, IL-23 and tumour
      necrosis factor (TNF)-alpha production. FICZ or ITE significantly inhibited the
      production of IL-1beta, IL-6, IL-23 and TNF-alpha, but induced IL-10 production
      by DCs derived from active BD patients and normal controls. FICZ or ITE-treated
      DCs significantly inhibited the T helper type 17 (Th17) and Th1 cell response.
      Activation of AhR either by FICZ or ITE inhibits DC differentiation, maturation
      and function. Further studies are needed to investigate whether manipulation of
      the AhR pathway may be used to treat BD or other autoimmune diseases. 

PMID- 24749688
TI  - microRNA-200b modulates microglia-mediated neuroinflammation via the cJun/MAPK
      pathway.
AB  - Chronic activation of microglia, the macrophages of the CNS, has been shown to
      enhance neuronal damage because of excessive release of proinflammatory cytokines
      and neurotoxic molecules in a number of neurodegenerative diseases. Recent
      reports showed altered microRNA (miRNA) expression in immune-mediated
      pathologies, thus suggesting that miRNAs modulate expression of genes involving
      immune responses. This study demonstrates that miRNA-200b is expressed in
      microglia and modulates inflammatory response of microglia by regulating mitogen
      activated protein kinase pathway. miRNA-200b expression was found to be down
      regulated in activated microglia in vivo (traumatic brain injury rat model) and
      in vitro. A luciferase assay and loss- and gain-of-function studies revealed c
      Jun, the transcription factor of cJun-N terminal kinase (JNK) mitogen-activated
      protein kinase pathway to be the target of miR-200b. Knockdown of miR-200b in
      microglia increased JNK activity along with an increase in pro-inflammatory
      cytokines, inducible nitric oxide synthase expression and nitric oxide (NO)
      production. Conversely, over-expression of miRNA-200b in microglia resulted in a
      decrease in JNK activity, inducible nitric oxide synthase expression, NO
      production and migratory potential of activated microglia. Furthermore, miR-200b
      inhibition resulted in increased neuronal apoptosis after treatment of neuronal
      cells with conditioned medium obtained from microglial culture. Taken together,
      these results indicate that miRNA-200b modulates microglial inflammatory process
      including cytokine secretion, NO production, migration and neuronal survival.

PMID- 24749689
TI  - Clonal diversity in biofilm formation by Enterococcus faecalis in response to
      environmental stress associated with endodontic irrigants and medicaments.
AB  - AIM: To determine whether clonal diversity within E. faecalis affects biofilm
      formation when exposed to antimicrobial compounds found in endodontic medicaments
      and irrigants. METHODOLOGY: Five human isolates of E. faecalis were compared;
      biofilms were grown in microtitre trays in the presence of sodium hypochlorite,
      calcium hydroxide, chlorhexidine, tetracycline or clindamycin. Biofilms were
      quantified by staining with crystal violet and optical density determined with a
      microplate reader. Slime production (an amorphous extracellular matrix comprising
      polysaccharides, glycoproteins and glycolipids loosely attached to the cell
      surface) was determined qualitatively by growth on Congo red agar plates. Linear
      mixed models were used to examine whether medicaments affected biofilm growth of
      the isolates in the presence of the medicaments or irrigants. RESULTS: Overall,
      different endodontic antimicrobials significantly altered biofilm growth in E.
      faecalis isolates. Two E. faecalis isolates significantly (P < 0.0001) increased
      biofilm formation in the presence of tetracycline and one in the presence of
      NaOCl (P = 0.018). Qualitatively, slime production also varied between isolates
      and correlated with biofilm production. CONCLUSIONS: When subjected to sub
      minimum inhibitory concentration (MIC) levels of antimicrobial compounds found in
      endodontic medicaments, E. faecalis isolates demonstrated significant clonal
      variation in their capacity to form biofilms. Interestingly, there was a
      correlation between slime production and the ability of isolates to form a
      biofilm in the presence of antimicrobials. The results indicate that isolates of
      E. faecalis that form biofilms in response to endodontic medicaments may be more
      likely to survive endodontic treatment.

PMID- 24749690
TI  - Fifty years' development and future perspectives of psychiatric register
      research.
AB  - OBJECTIVE: This article illustrates the development of psychiatric register
      research and discusses the strengths, limitations, and possible directions for
      future activities. METHOD: Examples illustrating the development from the post
      World War II introduction of psychiatric register research until today are
      selected. RESULTS: The strengths of register research are seen especially within
      health service. Until recently, when starting linking registers to biobanks,
      register research had limited value in cause-seeking. Register research benefits
      from the possibilities for following identifiable persons over long time
      (lifelong) and the possibilities for linking to other registers and databases.
      Important limitations of register research are the heterogeneity and questionable
      validity of the clinical data collected. CONCLUSION: Future register research can
      go in the direction of big is beautiful collecting data from all possible sources
      creating giga-registers. In that case, low data quality will still be an unsolved
      problem. Or it can take the direction of smaller local clinical databases which
      has many advantages, for example, integrating clinical knowledge and experience
      into register research. However, in that case, registers will not be able to deal
      with rare conditions and diseases.

PMID- 24749691
TI  - Pharmacokinetics and safety of firocoxib after oral administration of repeated
      consecutive doses to neonatal foals.
AB  - The purpose of this study was to determine the pharmacokinetics and safety
      profile of firocoxib in neonatal foals. Seven healthy foals were administered 0.1
      mg/kg firocoxib orally q24 h for nine consecutive days, commencing at 36 h of
      age. Blood was collected for firocoxib analysis using high-pressure liquid
      chromatography with fluorescence detection at 0 (dose #1 only), 0.25, 0.5, 1, 2,
      4, 8, 16, and 24 h after doses 1, 5, and 9. For all other doses (2, 3, 4, 6, 7,
      and 8), blood was collected immediately prior to the next dose (24 h trough).
      Elimination samples (36, 48, 72, 96, 120, and 144 h) were collected after dose 9.
      Safety was assessed via physical examinations, body weight measurements,
      gastroscopy, complete blood count, plasma biochemistry and urinalysis. Firocoxib
      was rapidly absorbed following oral administration with minimal accumulation
      after repeat dosing. After the final dose, the terminal half-life was
      approximately 11 h. Firocoxib was below the limit of detection (<2.5 ng/mL) in
      plasma 72 h after the final dose. No significant abnormalities were found on
      blood analyses, urinalysis, or gastroscopy. This study demonstrated that
      firocoxib is absorbed in neonatal foals with no demonstrable adverse effects
      after repeated doses of 0.1 mg/kg. 

PMID- 24749692
TI  - Ethanolic extracts of Tinospora cordifolia and Alstonia scholaris show
      antimicrobial activity towards clinical isolates of methicillin-resistant and
      carbapenemase-producing bacteria.
AB  - The aim of this study was to determine the in vitro antimicrobial activity of
      crude extracts of three plants from Ayurveda tradition (Tinospora cordifolia,
      Alstonia scholaris, Crataeva nurvala) against reference microbial strains and
      clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA) and
      carbapenemase-producing Klebsiella pneumoniae. IC50 values were obtained by micro
      dilution methods meeting the requirements of the NCCLS standard. The cytotoxicity
      of the extracts was also investigated on a mammalian cell line. Extracts
      displayed a variable degree of antimicrobial activity and did not interfere with
      mammalian cell proliferation. T. cordifolia and A. scholaris exhibited a higher
      inhibitory activity against clinical isolates of MRSA and carbapenemase-producing
      K. pneumoniae compared with reference strains, while C. nurvala exhibited a
      different behaviour. An antifungal activity towards Candida albicans was observed
      for A. scholaris extract. Results indicate that constituents from T. cordifolia
      and A. scholaris may be a potential source of new therapeutic strategies for
      infectious diseases. 

PMID- 24749693
TI  - Risk factors for facial melasma in women: a case-control study.
AB  - BACKGROUND: Melasma is a localized chronic acquired hypermelanosis, common in
      adult women and which has an important impact on their life quality. Its
      pathology is unknown, despite some recognized triggering factors. OBJECTIVE: To
      evaluate risk factors for developing facial melasma in women. METHODS: This was a
      case-control study involving adult women with or without facial melasma, paired
      by age. Variables were grouped into hierarchical levels: personal characteristic
      data, exposure variables, links to hormonal stimuli and the State-Trait Anxiety
      Inventory questionnaire, Brazilian version. The data were analysed using
      conditional multiple logistic regression. RESULTS: We evaluated 207 patients and
      207 controls. The mean age was 38 years. Cases differed from controls for
      phototype, Amerindian ancestry [odds ratio (OR) 2.59], years of beach or rural
      residence (OR 1.06), time exposed to sun at work (OR 1.65), time exposed to sun
      in leisure activities (OR 1.04), antidepressant/anxiolytic use (OR 4.96),
      menstrual irregularity (OR 3.83), pregnancy history (OR 3.59), years of oral
      contraceptive use (OR 1.23) and anxiety scores (OR 1.08). A family history of
      melasma was reported in 61% of cases and 13% of controls (OR 10.40). CONCLUSIONS:
      Facial melasma is independently associated with elements linked to pigmentation
      capacity, family ancestry, chronic sun exposure, sexual hormone stimuli,
      psychotropics and anxiety traits.

PMID- 24749694
TI  - Density-dependent intraspecific aggression regulates survival in northern
      Yellowstone wolves (Canis lupus).
AB  - Understanding the population dynamics of top-predators is essential to assess
      their impact on ecosystems and to guide their management. Key to this
      understanding is identifying the mechanisms regulating vital rates. Determining
      the influence of density on survival is necessary to understand the extent to
      which human-caused mortality is compensatory or additive. In wolves (Canis
      lupus), empirical evidence for density-dependent survival is lacking. Dispersal
      is considered the principal way in which wolves adjust their numbers to prey
      supply or compensate for human exploitation. However, studies to date have
      primarily focused on exploited wolf populations, in which density-dependent
      mechanisms are likely weak due to artificially low wolf densities. Using 13 years
      of data on 280 collared wolves in Yellowstone National Park, we assessed the
      effect of wolf density, prey abundance and population structure, as well as
      winter severity, on age-specific survival in two areas (prey-rich vs. prey-poor)
      of the national park. We further analysed cause-specific mortality and explored
      the factors driving intraspecific aggression in the prey-rich northern area of
      the park. Overall, survival rates decreased during the study. In northern
      Yellowstone, density dependence regulated adult survival through an increase in
      intraspecific aggression, independent of prey availability. In the interior of
      the park, adult survival was less variable and density-independent, despite
      reduced prey availability. There was no effect of prey population structure in
      northern Yellowstone, or of winter severity in either area. Survival was similar
      among yearlings and adults, but lower for adults older than 6 years. Our results
      indicate that density-dependent intraspecific aggression is a major driver of
      adult wolf survival in northern Yellowstone, suggesting intrinsic density
      dependent mechanisms have the potential to regulate wolf populations at high
      ungulate densities. When low prey availability or high removal rates maintain
      wolves at lower densities, limited inter-pack interactions may prevent density
      dependent survival, consistent with our findings in the interior of the park.

PMID- 24749695
TI  - Polydiacetylene-enclosed near-infrared fluorescent semiconducting polymer dots
      for bioimaging and sensing.
AB  - Semiconducting polymer dots (P-dots) recently have emerged as a new type of
      ultrabright fluorescent probe with promising applications in biological imaging
      and detection. With the increasing desire for near-infrared (NIR) fluorescing
      probes for in vivo biological measurements, the currently available NIR-emitting
      P-dots are very limited and the leaching of the encapsulated dyes/polymers has
      usually been a concern. To address this challenge, we first embedded the NIR dyes
      into the matrix of poly[(9,9-dioctylfluorene)-co-2,1,3-benzothiadiazole-co-4,7
      di(thiophen-2-yl)-2,1,3-benzothiadiazole] (PF-BT-DBT) polymer and then enclosed
      the doped P-dots with polydiacetylenes (PDAs) to avoid potential leakage of the
      entrapped NIR dyes from the P-dot matrix. These PDA-enclosed NIR-emitting P-dots
      not only emitted much stronger NIR fluorescence than conventional organic
      molecules but also exhibited enhanced photostability over CdTe quantum dots, free
      NIR dyes, and gold nanoclusters. We next conjugated biomolecules onto the surface
      of the resulting P-dots and demonstrated their capability for specific cellular
      labeling without any noticeable nonspecific binding. To employ this new class of
      material as a facile sensing platform, an easy-to-prepare test paper, obtained by
      soaking the paper into the PDA-enclosed NIR-emitting P-dot solution, was used to
      sense external stimuli such as ions, temperature, or pH, depending on the surface
      functionalization of PDAs. We believe these PDA-coated NIR-fluorescing P-dots
      will be very useful in a variety of bioimaging and analytical applications. 

PMID- 24749696
TI  - On the role of exponential smoothing in circadian dosimetry.
AB  - The effects lighting has on health through modulation of circadian rhythms are
      becoming increasingly well documented. Data are still needed to show how light
      exposures are influenced by architecture and lighting design and circadian
      dosimetry analyses should provide duration, phase and amplitude measures of 24 h
      exposure profiles. Exponential smoothing is used to derive suitable metrics from
      24 h light measurements collected from private dwellings. A further application
      of these modified exposure time series as physiological models of the light drive
      is discussed. Unlike previous light drive models, the dose rate persists into
      periods of darkness following exposures. Comparisons to long duration exposure
      studies suggest this type of persistent light drive model could be incorporated
      into contemporary physiological models of the human circadian oscillator. 

PMID- 24749697
TI  - Gene expression profiles of central nervous system lymphoma predict poor survival
      in patients with diffuse large B-cell lymphoma.

PMID- 24749698
TI  - Modulation of autophagy for the treatment of liver diseases.
AB  - INTRODUCTION: Autophagy is a cellular process essential for survival and
      homeostasis that confers cellular protection toward a wide range of deleterious
      stimuli. It has a highly complex regulation with several autophagic proteins also
      belonging to other main signaling pathways as cell proliferation or apoptosis. In
      addition, autophagy has an important role in cell metabolism. Interest in the
      study of this process is rapidly rising and, in the past few years, autophagy has
      been implicated in a variety of hepatic diseases. AREAS COVERED: The review
      covers the research and investigational use of pharmacological strategies that
      modify autophagy in the treatment of liver diseases. Autophagy modulation in
      steatosis, steatohepatitis, viral hepatitis, fibrogenesis, cirrhosis,
      hepatocellular carcinoma and ischemia/reperfusion injury will be described,
      critically analyzed and discussed. Papers included in the present manuscript were
      selected from the PubMed search: liver + (macro)autophagy + each of the
      pathologies described above. EXPERT OPINION: The complexity of autophagy creates
      significant controversy on the potential of its pharmacological modulation. A
      major requirement for drugs regulating autophagy in the treatment of liver
      diseases is that these should be liver-specific; moreover, they should primarily
      target one specific hepatic cell type.

PMID- 24749699
TI  - Control of multi-drug-resistant pathogens with non-thermal-plasma-treated
      alginate wound dressing.
AB  - BACKGROUND: Non-thermal dielectric-barrier discharge plasma (non-thermal plasma)
      is being investigated for use in wound healing. Alginate gel, already in clinical
      use, is non-toxic but has no meaningful antimicrobial property. This study
      reports that a non-thermal-plasma-treated alginate wound dressing has strong
      antimicrobial properties. METHODS: Alginate gel was treated with non-thermal
      plasma in room air and inoculated with bacterial pathogens. At 15 min after this,
      bacterial cell viability was determined by colony assay or 2,3-bis-(2-methoxy-4-
      nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide (XTT) assay. The anti-biofilm
      efficacy of the non-thermal-plasma-treated alginate gel was investigated and the
      treated gel was tested against vascular endothelial cells for a cytotoxic effect.
      The proliferation and migration of bacterial cells before and after exposure to
      the treated gel were investigated with an in vitro wound testing assay. Scanning
      electron microscopy was used to observe changes in the gel surface associated
      with exposure to bacterial pathogens. The treated gel was tested against
      Acinetobacter baumannii, Escherichia coli, Staphylococcus aureus, S. epidermidis,
      Candida albicans, and C. glabrata as representative pathogens (at 10(6)-10(9)
      colony-forming units [CFU]/mL), and the thickness of a plasma-treated gel
      dressing and distance between a glass dielectric-barrier discharge plasma probe
      and the gel surface were kept constant. RESULTS: Non-thermal-plasma-treated
      alginate gel exhibited a strong biocidal property and inactivated all of the
      pathogens included in the study at counts of 10(8) CFU/mL and within 15 sec of
      treatment. The treated gel inactivated 10(9) CFU/mL of the organisms within 1
      min, and 3 min of exposure to the treated gel inactivated pathogens embedded in
      biofilms. The plasma-treated gel showed no significant cytotoxicity, and
      endothelial cells exposed to the treated gel proliferated and migrated well
      across a wound area over a period of time. Dressings made with the treated gel
      retained their biocidal effects for about a month. Scanning electron microscopy
      showed no damage to the surfaces of treated gels, but damage to the bacterial
      pathogens on plasma exposure. CONCLUSION: A non-thermal-plasma-treated alginate
      gel dressing has the clinical potential to decontaminate wounds, prevent surgical
      site infection, and promote wound healing.

PMID- 24749700
TI  - High-fidelity specialty mental health probation improves officer practices,
      treatment access, and rule compliance.
AB  - Many probation agencies in the United States assign offenders with mental illness
      to relatively small specialty caseloads supervised by officers with relevant
      training, rather than to large general caseloads. Specialty caseloads are
      designed to improve the process and outcomes of probation, largely by linking
      these probationers with psychiatric treatment and avoiding unnecessary
      violations. In this multimethod, longitudinal matched trial, we tested whether a
      prototypical specialty agency (n = 183) differed from a traditional agency (n =
      176) in officers' practices, probationers' treatment access, and probationers'
      rule violations. The specialty agency yielded significantly (a) better officer
      practices (e.g., problem solving rather than sanction threats; higher quality
      relationships with probationers; more boundary spanning), (b) greater rates of
      treatment involvement, and (c) lower rates of violation reports than the
      traditional agency. Additionally, officers' use of sanctions and threats
      increased probationers' risk of incurring a probation violation, whereas high
      quality officer-probationer relationships protected against this outcome. When
      implemented with fidelity, specialty mental health caseloads improved the
      supervision process for this high-need group.

PMID- 24749701
TI  - Ab initio study on the ground and low-lying states of BAlk (Alk = Li, Na, K)
      molecules.
AB  - The potential energy curves (PECs) and dipole moment functions of (1)Pi, (3)Pi,
      (1)Sigma(+), and (3)Sigma(+) states of BAlk (Alk = Li, Na, K) are calculated
      using multireference configuration interaction method and large all-electron
      basis sets. The effects of inner-shell correlation electron for BAlk are
      considered. The ro-vibrational energy levels are obtained by solving the
      Schrodinger equation of nuclear motion based on the ab initio PECs. The
      spectroscopic parameters are determined from the ro-vibrational levels with
      Dunham expansion. The PECs are fitted into analytical potential energy functions
      using the Morse long-range potential function. The dipole moment functions for
      the states of BAlk are presented. The transition dipole moments for (1)Sigma(+) 
      > (1)Pi and (3)Sigma(+) -> (3)Pi states of BAlk are obtained. The interactions
      between the outermost electron of Alk and B 2p electrons for (1)Pi, (3)Pi,
      (1)Sigma(+), and (3)Sigma(+) states are also analyzed, respectively. 

PMID- 24749702
TI  - Comparative time efficiency of aligner therapy and conventional edgewise braces.
AB  - OBJECTIVE: To compare the time efficiency of aligner therapy (ALT) and
      conventional edgewise braces (CEB) based on large samples of patients treated by
      the same highly experienced orthodontist, with the same treatment goals for both
      groups of patients. MATERIALS AND METHODS: The retrospective portion of the study
      evaluated 150 CEB patients who were matched, based on mandibular crowding and
      number of rotated teeth, to 150 ALT patients. All records were obtained at one
      orthodontist's office. All of the patients had mild-to-moderate Class I
      malocclusions (<=5 mm incisor crowding) and were treated nonextraction. Age,
      gender, total treatment time, total number of appointments, types of
      appointments, materials used, mandibular crowding, and number of rotated teeth
      were recorded from the patients' records. The prospective portion of the study
      timed the various types of appointments for both treatments with a stopwatch.
      RESULTS: Compared to ALT, CEB required significantly (P<.01) more visits
      (approximately 4.0), a longer treatment duration (5.5 months), more emergency
      visits (1.0), greater emergency chair time (7.0 minutes), and greater total chair
      time (93.4 minutes). However, ALT showed significantly (P<.01) greater total
      material costs and required significantly more total doctor time than CEB
      (P<.01). CONCLUSIONS: Whether the greater time efficiency of ALT offsets the
      greater material costs and doctor time required depends on the experience of the
      orthodontist and the number of ALT case starts.

PMID- 24749703
TI  - Defining and framing orthodontitis: a new term in orthodontics.

PMID- 24749705
TI  - Re: Impact of malocclusion on the quality of life of Saudi children. The Angle
      Orthodontist 2013(6) 1043-1048.

PMID- 24749706
TI  - Re: Impact of malocclusion on the quality of life of Saudi children. The Angle
      Orthodontist 2013(6) 1043-1048.

PMID- 24749707
TI  - Re: Efficacy of three hygienic protocols in reducing biofilm adherence to
      removable thermoplastic appliance. The Angle Orthodontist 2014(1) 161-170.

PMID- 24749708
TI  - RE: response to: Efficacy of three hygienic protocols in reducing biofilm
      adherence to removable thermoplastic appliance. The Angle Orthodontist 2014(1)
      161-170.

PMID- 24749709
TI  - Re: Effects of long-term occlusal hypofunction and its recovery on the
      morphogenesis of molar roots and the periodontium in rats. The Angle Orthodontist
      2013(4) 597-604.

PMID- 24749710
TI  - Re: response to: Effects of long-term occlusal hypofunction and its recovery on
      the morphogenesis of molar roots and the periodontium in rats. The Angle
      Orthodontist 2013(4) 597-604.

PMID- 24749712
TI  - Diffusion-weighted MR imaging in laryngeal and hypopharyngeal carcinoma:
      association between apparent diffusion coefficient and histologic findings.
AB  - PURPOSE: To investigate the relationship between the histologic characteristics
      of head and neck squamous cell carcinoma and apparent diffusion coefficient (ADC)
      at diffusion-weighted magnetic resonance (MR) imaging. MATERIALS AND METHODS: The
      institutional ethics committee approved this study and waived informed consent.
      In head and neck squamous cell carcinoma, local failure after chemotherapy and/or
      radiation therapy correlates with pretreatment ADC. However, the histopathologic
      basis of this correlation remains unclear. In this study, 16 patients with head
      and neck squamous cell carcinoma were enrolled (median age, 60 years; range, 49
      78 years). Before undergoing total laryngectomy, patients underwent 1.5-T
      diffusion-weighted MR imaging. After resection, whole-mount hematoxylin-eosin
      stained sections were registered to the MR images. Cellular density; nuclear,
      cytoplasmic, and stromal area; and nuclear-cytoplasmic ratio within the tumor
      were calculated by using image-based segmentation on four consecutive slices.
      Mean ADC of the corresponding tumor region was calculated. Spearman correlations
      between ADC and histologic characteristics were calculated. RESULTS: ADC was
      significantly and inversely correlated with cell density (n = 16, r = -0.57, P =
      .02), nuclear area (n = 12, r = -0.64, P = .03), and nuclear-cytoplasmic ratio (n
      = 12, r = -0.77, P <= .01). ADC was significantly and positively correlated with
      percentage area of stroma (n = 12, r = 0.69, P = .01). Additionally, the
      percentage area of stroma was strongly interdependent with the percentage area of
      nuclei (n = 12, r = -0.97, P <= .01). CONCLUSION: ADC was significantly
      correlated with cellularity, stromal component, and nuclear-cytoplasmic ratio.
      The positive correlation of ADC and stromal component suggests that the poor
      prognostic value of high pretreatment ADC might partly be attributed to the tumor
      stroma component, a known predictor of local failure.

PMID- 24749713
TI  - Fused X-ray and MR imaging guidance of intrapericardial delivery of
      microencapsulated human mesenchymal stem cells in immunocompetent swine.
AB  - PURPOSE: To assess intrapericardial delivery of microencapsulated, xenogeneic
      human mesenchymal stem cells (hMSCs) by using x-ray fused with magnetic resonance
      (MR) imaging (x-ray/MR imaging) guidance as a potential treatment for ischemic
      cardiovascular disease in an immunocompetent swine model. MATERIALS AND METHODS:
      All animal experiments were approved by the institutional animal care and use
      committee. Stem cell microencapsulation was performed by using a modified
      alginate-poly-l-lysine-alginate encapsulation method to include 10% (wt/vol)
      barium sulfate to create barium-alginate microcapsules (BaCaps) that contained
      hMSCs. With x-ray/MR imaging guidance, eight female pigs (approximately 25 kg)
      were randomized to receive either BaCaps with hMSCs, empty BaCaps, naked hMSCs,
      or saline by using a percutaneous subxiphoid approach and were compared with
      animals that received empty BaCaps (n = 1) or BaCaps with hMSCs (n = 2) by using
      standard fluoroscopic delivery only. MR images and C-arm computed tomographic
      (CT) images were acquired before injection and 1 week after delivery. Animals
      were sacrificed immediately or at 1 week for histopathologic validation. Cardiac
      function between baseline and 1 week after delivery was evaluated by using a
      paired Student t test. RESULTS: hMSCs remained highly viable (94.8% +/- 6) 2 days
      after encapsulation in vitro. With x-ray/MR imaging, successful intrapericardial
      access and delivery were achieved in all animals. BaCaps were visible
      fluoroscopically and at C-arm CT immediately and 1 week after delivery. Whereas
      BaCaps were free floating immediately after delivery, they consolidated into a
      pseudoepicardial tissue patch at 1 week, with hMSCs remaining highly viable
      within BaCaps; naked hMSCs were poorly retained. Follow-up imaging 1 week after x
      ray/MR imaging-guided intrapericardial delivery showed no evidence of pericardial
      adhesion and/or effusion or adverse effect on cardiac function. In
      contradistinction, BaCaps delivery with x-ray fluoroscopy without x-ray/MR
      imaging (n = 3) resulted in pericardial adhesions and poor hMSC viability after 1
      week. CONCLUSION: Intrapericardial delivery of BaCaps with hMSCs leads to high
      cell retention and survival. With x-ray/MR imaging guidance, intrapericardial
      delivery can be performed safely in the absence of preexisting pericardial
      effusion to provide a novel route for cardiac cellular regenerative therapy.

PMID- 24749714
TI  - Management of nodules with initially nondiagnostic results of thyroid fine-needle
      aspiration: can we avoid repeat biopsy?
AB  - PURPOSE: To identify demographic and ultrasonographic (US) features associated
      with malignancy after initially nondiagnostic results of fine-needle aspiration
      (FNA) to help clarify the role of repeat FNA, surgical excision, or serial US in
      these nodules. MATERIALS AND METHODS: This study was HIPAA compliant and
      institutional review board approved; informed consent was waived. Thyroid nodules
      (n = 5349) that underwent US-guided FNA in 2004-2012 were identified; 393 were
      single nodules with nondiagnostic FNA results but adequate cytologic, surgical,
      or US follow-up. Demographic information and diameters and volume at US at first
      biopsy were modeled with malignancy as outcome through medical record review.
      Exact logistic regression was used to model malignancy outcomes, demographic
      comparisons with age were made (Student t test, Satterthwaite test), and
      proportion confidence intervals (CIs) were estimated (Clopper-Pearson method).
      RESULTS: Of 393 nodules with initially nondiagnostic results, nine malignancies
      (2.3%) were subsequently diagnosed with repeat FNA (n = 2, 0.5%) or surgical
      pathologic examination (n = 7, 1.8%), 330 (84.0%) were benign, and 54 (13.7%)
      were stable or decreased in size at serial US (mean follow-up, 3.0 years; median,
      2.5 years; range, 1.0-7.8 years). Patients with malignancies were significantly
      older (mean age, 62.7 years; median, 64 years; range, 47-77 years) than those
      without (mean age, 55.4 years; median, 57 years; range, 12-94 years; P = .0392).
      Odds of malignancy were 4.2 times higher for men versus women (P = .045) and
      increased significantly for each 1-cm increase in anteroposterior, minimum, and
      mean nodule diameter (1.78, 2.10, and 1.96, respectively). In 393 nodules, no
      malignancies were detected in cystic or spongiform nodules (both, n = 11, 2.8%;
      95% CI: 1.4%, 5.0%), nodules with eggshell calcifications (n = 9, 2.3%; 95% CI:
      1.1%, 4.3%), or indeterminate echogenic foci (n = 39, 9.9%; 95% CI: 7.2%, 13.3%).
      CONCLUSION: Very few malignancies were diagnosed with repeat FNA following
      nondiagnostic FNA results (two of 336, 0.6%); therefore, clinical and US follow
      up may be more appropriate than repeat FNA following nondiagnostic biopsy
      results.

PMID- 24749715
TI  - Assessment of myocardial reactivity to controlled hypercapnia with free-breathing
      T2-prepared cardiac blood oxygen level-dependent MR imaging.
AB  - PURPOSE: To examine whether controlled and tolerable levels of hypercapnia may be
      an alternative to adenosine, a routinely used coronary vasodilator, in healthy
      human subjects and animals. MATERIALS AND METHODS: Human studies were approved by
      the institutional review board and were HIPAA compliant. Eighteen subjects had
      end-tidal partial pressure of carbon dioxide (PetCO2) increased by 10 mm Hg, and
      myocardial perfusion was monitored with myocardial blood oxygen level-dependent
      (BOLD) magnetic resonance (MR) imaging. Animal studies were approved by the
      institutional animal care and use committee. Anesthetized canines with (n = 7)
      and without (n = 7) induced stenosis of the left anterior descending artery (LAD)
      underwent vasodilator challenges with hypercapnia and adenosine. LAD coronary
      blood flow velocity and free-breathing myocardial BOLD MR responses were measured
      at each intervention. Appropriate statistical tests were performed to evaluate
      measured quantitative changes in all parameters of interest in response to
      changes in partial pressure of carbon dioxide. RESULTS: Changes in myocardial
      BOLD MR signal were equivalent to reported changes with adenosine (11.2% +/- 10.6
      [hypercapnia, 10 mm Hg] vs 12% +/- 12.3 [adenosine]; P = .75). In intact canines,
      there was a sigmoidal relationship between BOLD MR response and PetCO2 with most
      of the response occurring over a 10 mm Hg span. BOLD MR (17% +/- 14 [hypercapnia]
      vs 14% +/- 24 [adenosine]; P = .80) and coronary blood flow velocity (21% +/- 16
      [hypercapnia] vs 26% +/- 27 [adenosine]; P > .99) responses were similar to that
      of adenosine infusion. BOLD MR signal changes in canines with LAD stenosis during
      hypercapnia and adenosine infusion were not different (1% +/- 4 [hypercapnia] vs
      6% +/- 4 [adenosine]; P = .12). CONCLUSION: Free-breathing T2-prepared myocardial
      BOLD MR imaging showed that hypercapnia of 10 mm Hg may provide a cardiac
      hyperemic stimulus similar to adenosine.

PMID- 24749716
TI  - Cognitive vulnerability to bipolar disorder in offspring of parents with bipolar
      disorder.
AB  - BACKGROUND: Bipolar disorder is a highly heritable illness, with a positive
      family history robustly predictive of its onset. It follows that studying
      biological children of parents with bipolar disorder may provide information
      about developmental pathways to the disorder. Moreover, such studies may serve as
      a useful test of theories that attribute a causal role in the development of mood
      disorders to psychological processes. METHOD: Psychological style (including self
      esteem, coping style with depression, domain-specific risk-taking, sensation
      seeking, sensitivity to reward and punishment, and hypomanic personality and
      cognition) was assessed in 30 offspring of bipolar parents and 30 children of
      well parents. Parents of both child groups completed identical assessments.
      RESULTS: Although expected differences between parents with bipolar disorder and
      well parents were detected (such as low self-esteem, increased rumination, high
      sensitivity to reward and punishment), offspring of bipolar parents were, as a
      group, not significantly different from well offspring, apart from a modest trend
      towards lower adaptive coping. When divided into affected and non-affected
      subgroups, both groups of index children showed lower novelty-seeking. Only
      affected index children showed lower self-esteem, increased rumination,
      sensitivity to punishment, and hypomanic cognitions. Notably, these processes
      were associated with symptoms of depression. CONCLUSION: Psychological
      abnormalities in index offspring were associated with having met diagnostic
      criteria for psychiatric illnesses and the presence of mood symptoms, rather than
      preceding them. Implications of the present findings for our understanding of the
      development of bipolar disorder, as well as for informing early interventions,
      are discussed.

PMID- 24749717
TI  - Plasmids and evolutionary rescue by drug resistance.
AB  - Antibiotic resistance provides evolutionary rescue for bacterial populations
      under the threat of extinction through antibiotics. It can arise de novo through
      mutation in the population, or be obtained from other bacterial populations via
      the transfer of a resistance-conferring plasmid. We use stochastic modeling
      methods to establish whether the most likely source of rescue is via a plasmid or
      via the chromosome, and show that contrary to what is assumed plasmids are not
      necessarily beneficial locations for resistance genes. Competition at the plasmid
      level of selection is of great importance-the spread of a resistant plasmid in
      the population can be slowed or entirely stopped by a nonresistant version of the
      same plasmid. We suggest that future studies on antibiotic-resistant plasmids
      should explicitly consider competition at this level of selection.

PMID- 24749718
TI  - Visual Impairment in Pseudoxanthoma Elasticum: A Survey of 40 Patients.
AB  - BACKGROUND: Pseudoxanthoma elasticum is an inherited disorder of connective
      tissue characterized, among other symptoms, by impaired vision. OBJECTIVE: To
      evaluate the nature and age of onset of ophthalmologic manifestations in
      pseudoxanthoma elasticum. PATIENTS AND METHODS: Forty consecutive patients
      affected with pseudoxanthoma elasticum underwent measurements of their refractive
      error and visual acuity, together with slit-lamp examination. RESULTS: The mean
      age of the patients (8 M, 32 F) was 43.35 years. Fifty-seven eyes (33 patients,
      mean age: 40.75 years) had a BCVA >20/50 whereas 23 eyes in 16 patients (mean
      age: 53.31 years) had <=20/50. Seven patients (17.50%), all but one over 52 years
      old, were visually disabled. BCVA <=20/50 in at least one eye was observed in
      73.33% of patients of 52 years old or older and in 20.00% of patients younger
      than 52, respectively. Angioid streaks were observed in 75 eyes (93.75%) and
      extended toward the macula in 51 eyes from 29 patients. Macular involvement was
      observed for the first time at a mean age of 44.28 years. Neovascularization was
      observed in 28 eyes (17 patients; mean age: 51.70 years), all with poor BCVA.
      CONCLUSION: Macular choroidal neovascularization is frequent in pseudoxanthoma
      elasticum, and accounts for the poor ophthalmologic natural history of the
      disease. Patients should be advised to self-monitor their visual acuity using the
      Amsler grid. The frequency of choroidal neovascularization appears age-dependent,
      suggesting that bi-yearly fundus examination is appropriate in young patients
      whereas patients older than 40 should be examined twice a year.

PMID- 24749719
TI  - The no conclusion intervention for couples in conflict.
AB  - Dealing with difference is central to all couple therapy. This article presents
      an intervention designed to assist couples in handling conflict. Central to this
      approach is the acceptance that most conflicts cannot be solved. Couples are in
      need of a different understanding of couples conflict. This understanding is
      found in the analysis of love in context and in relational dialectics. Couples
      are guided through different steps: deciding on the valence of the issue as
      individuals, helping them decide which differences can be resolved and which
      issues demand new ways of living with the inevitable, and the introduction in the
      suggested no conclusion dialogue. This article briefly describes the five day
      intensive couple therapy program, in which the no intervention is embedded. The
      theoretical foundation of the intervention, followed by the step by step
      description of the intervention forms the major part of the article. A case
      vignette illustrates this approach. 

PMID- 24749720
TI  - Hepatoprotective sesquiterpenes and rutinosides from Murraya koenigii (L.)
      Spreng.
AB  - Three new sesquiterpenes (1-3) and two new rutinosides (4 and 5) along with 17
      known compounds (6-22) were isolated from the leaves of Murraya koenigii (L.)
      Spreng. The new compounds were elucidated as (3R,5S,6R)-3,5,6-trihydroxy-1,1,5
      trimethylcyclohexyl-8-butyn-9-one (1), (8E,9R)-ethyl-7-(3S,5R,6S)-3,6-dihydroxy
      1,1,5-trimethylcyclohexyl-9-hydroxybut-8-enoate (2), (3R)-3-O-beta-D-glucoside-6'
      D-apiose-beta-ionone (3), 4-O-beta-D-rutinosyl-3-methoxyphenyl-1-propanone (4),
      and 1-O-beta-D-rutinosyl-2(R)-ethyl-1-pentanol (5) based on their spectroscopic
      data. Compounds 1, 4, 5, 18, and 21 (10 MUM) exhibited moderate hepatoprotective
      activities.

PMID- 24749721
TI  - Genetic diversity and population structure of Mongolian domestic Bactrian camels
      (Camelus bactrianus).
AB  - The tradition of animal husbandry in the context of a nomadic lifestyle has been
      of great significance in the Mongolian society. Both Bactrian camels and horses
      have been invaluable for the survival and development of human activities in the
      harsh arid environment of the Mongolian steppe. As camels offer unique and
      sustainable opportunities for livestock production in marginal agro-ecological
      zones, we investigated the current genetic diversity of three local Mongolian
      camel breeds and compared their levels of variation with common native Mongolian
      camels distributed throughout the country. Based on mitochondrial and nuclear
      markers, we found levels of genetic diversity in Mongolian populations similar to
      that reported for Chinese Bactrian camels and for dromedaries. Little
      differentiation was detected between single breeds, except for a small group
      originating from the northwestern Mongolian Altai. We found neither high
      inbreeding levels in the different breeds nor evidence for a population decline.
      Although the Mongolian camel census size has severely declined over the past 20
      years, our analyses suggest that there still exists a stable population with
      adequate genetic variation for continued sustainable utilization.

PMID- 24749722
TI  - Helminths in the hygiene hypothesis: sooner or later?
AB  - There is increasing recognition that exposures to infectious agents evoke
      fundamental effects on the development and behaviour of the immune system.
      Moreover, where infections (especially parasitic infections) have declined,
      immune responses appear to be increasingly prone to hyperactivity. For example,
      epidemiological studies of parasite-endemic areas indicate that prenatal or early
      life experience of infections can imprint an individual's immunological
      reactivity. However, the ability of helminths to dampen pathology in established
      inflammatory diseases implies that they can have therapeutic effects even if the
      immune system has developed in a low-infection setting. With recent
      investigations of how parasites are able to modulate host immune pathology at the
      level of individual parasite molecules and host cell populations, we are now able
      to dissect the nature of the host-parasite interaction at both the initiation and
      recall phases of the immune response. Thus the question remains - is the
      influence of parasites on immunity one that acts primarily in early life, and at
      initiation of the immune response, or in adulthood and when recall responses
      occur? In short, parasite immunosuppression - sooner or later? 

PMID- 24749723
TI  - A standardized, bundled approach to providing geriatric-focused acute care.
AB  - OBJECTIVES: To determine whether a bundled intervention can increase detection of
      delirium and facilitate safer use of high-risk medications. DESIGN: Pre-post
      interventional trial. SETTING: Large academic medical center. PARTICIPANTS:
      Individuals aged 70 and older (n = 19,949) admitted between May 1, 2008,
      September 30, 2011. Individuals aged 80 and older admitted after April 26, 2010,
      received the intervention, those aged 80 and older admitted before were primary
      controls, and those aged 70 to 79 were concurrent controls. INTERVENTION: The
      intervention uses a checklist promoting delirium prevention, recognition and
      management, and modifies the computerized provider order entry system to provide
      care focused on elderly adults. MEASUREMENTS: Frequency of orders for activating
      the rapid response team for altered mental status, frequency of orders for
      haloperidol in excess of 0.5 mg or intravenous (IV) morphine in excess of 2 mg,
      and discharge disposition. RESULTS: Participants receiving the intervention had a
      mean age of 86.1 +/- 4.6; 58.2% were female. The number of orders to activate the
      rapid response team for altered mental status increased in participants receiving
      the bundle and in controls (odds ratio (OR) for the difference of differences =
      1.23 (95% confidence interval (CI) = 0.68-2.24, P = .49)). Participants receiving
      the bundle were less likely to receive more than 0.5 mg of IV, intramuscular, or
      oral haloperidol (OR = 0.60, 95% CI = 0.39-0.91, P = .02) and more than 2 mg of
      IV morphine (OR = 0.52, 95% CI = 0.42-0.63, P < .001). Participants who received
      the bundle were more likely to be discharged home than to extended care
      facilities (OR = 1.18, 95% CI = 1.04-1.35, P = .01). CONCLUSION: An intervention
      focused on delirium prevention and recognition by bedside staff combined with
      computerized decision support facilitates safer prescribing of high-risk
      medications and possibly results in less need for extended care.

PMID- 24749724
TI  - Anti-depressive activities and biotransformation of timosaponin B-III and its
      derivatives.
AB  - Timosaponin B-III (TB-III) is a steroidal saponin isolated from the rhizome of
      Anemarrhenae asphodeloides (Liliaceae). The biotransformation of TB-III by beta
      glucosidase was investigated. Three biotransformation products were isolated and
      their structures were identified as timosaponin B-III-a (M1), (20R,25S)-5beta
      spirostane-3beta-ol-3-O-beta-D-glucopyranosyl-(1 -> 2)-beta-D-galacopyanoside
      (M2) and timosaponin AIII (M3). Then the four compounds were evaluated for their
      anti-depressive activity in mice by the open field test, tail suspension test and
      forced swimming test. As a result, TB-III, M1 and M3 exhibited modest anti
      depressive activity. Structure-activity relationships were investigated and the
      preliminary conclusions are summarised as follows: the glycosyl at C-3 and C-26
      can increase the activity, the double bond between C-20 and C-22 might be
      important for the anti-depressive activity, the R-configuration at C-22 and S
      configuration at C-20 are necessary for its anti-depressive activity.

PMID- 24749725
TI  - Safety of biological therapies for psoriasis: effects on reproductive potential
      and outcomes in male and female patients.
AB  - The effects of biological therapies for psoriasis on pregnancy outcomes and
      lactation, and male fertility and mutagenicity are common concerns in the
      clinical setting. There is relatively little evidence to guide the clinician and
      patient. Here, we review the safety profile of the commonly used biological
      therapies for psoriasis in individuals of reproductive potential. Safety data
      were derived from large-scale registries, adverse event reporting databases,
      clinical trials and case reports. We assessed the effect of each therapy on
      adverse pregnancy outcomes including congenital malformations, and lactation with
      maternal administration, and male fertility and potential mutagenicity with
      paternal administration. We provide applicable guidance to inform clinician and
      patient before and after conception. 

PMID- 24749726
TI  - The physiological basis of synchronizing conversational rhythms: the role of the
      ventromedial prefrontal cortex.
AB  - OBJECTIVE: During conversation, people tend to converge and become more similar
      across discourse characteristics, such as producing similar speaking turn lengths
      and even similar words. This "conversational synchrony" enhances social
      affiliation and rapport. Here, we investigated the role of the ventromedial
      prefrontal cortex (vmPFC) in conversational synchrony. We focused on the vmPFC
      because this region is strongly implicated in social behaviors related to
      synchrony, such as empathy. METHOD: To examine the role of the vmPFC role in
      conversational synchrony, convergence of total words and words per turn were
      measured in the discourse of participants with bilateral vmPFC damage, healthy
      comparison participants (CP), and a brain-damaged comparison group with bilateral
      hippocampal damage (HPC) as they interacted with an unfamiliar partner. RESULTS:
      CP and HPC interactions displayed convergence as the interactants' productions of
      words and words per turn became more similar across the sessions. In striking
      contrast, vmPFC interactions did not display convergence for either variable. A
      follow-up experiment revealed the same lack of convergence in the interactions of
      vmPFC participants with a more familiar conversational partner. CONCLUSIONS: Our
      results suggest that vmPFC is a crucial part of the neurobiological system that
      supports the ability to synchronize conversational rhythms by dynamically
      adjusting behavior to the social environment.

PMID- 24749727
TI  - APOE and spatial navigation in amnestic MCI: results from a computer-based test.
AB  - OBJECTIVE: We investigated the association between APOE epsilon4 status and
      spatial navigation in patients with amnestic mild cognitive impairment (aMCI) and
      assessed the role of hippocampal volume in this association. METHOD: Participants
      were 74 patients with clinically confirmed aMCI (33 APOE epsilon4 noncarriers, 26
      heterozygous, and 15 homozygous epsilon4 carriers). Body-centered (egocentric)
      and world-centered (allocentric) spatial navigation in a computerized human
      analogue of the Morris Water Maze was assessed. Brain MRI with subsequent
      automated hippocampal volumetry was included. RESULTS: Groups were similar in
      neuropsychological profile. Controlling for age, sex, education, and free memory
      recall, the APOE epsilon4 carriers performed more poorly on all spatial
      navigation subtasks (ps < .05). APOE epsilon4 homozygotes performed worse than
      heterozygotes (p = .021). Right hippocampal volume accounted for the differences
      in allocentric and delayed subtasks (ps > .05), but not in the egocentric subtask
      (p < .001). CONCLUSIONS: Using an easy-to-use, computer-based tool to assess
      spatial navigation, we found spatial navigation deficits to worsen in a dose
      dependent manner as a function of APOE epsilon4 status. This was at least
      partially due to differences in right hippocampal volume.

PMID- 24749728
TI  - Inhibition during early adolescence predicts alcohol and marijuana use by late
      adolescence.
AB  - OBJECTIVE: Adolescent substance use has been associated with poorer
      neuropsychological functioning, but it is unclear if deficits predate or follow
      the onset of use. The goal of this prospective study was to understand how
      neuropsychological functioning during early adolescence could predict substance
      use by late adolescence. METHOD: At baseline, participants were 175 substance-use
      naive healthy 12- to 14-year-olds (41% female) recruited from local schools.
      Participants completed extensive interviews and neuropsychological tests. Each
      year, participants' substance use was assessed. By late adolescence (ages 17 to
      18), 105 participants transitioned into substance use and 75 remained substance
      naive. Hierarchical linear regressions examined how baseline cognitive
      performance predicted subsequent substance use, controlling for common substance
      use risk factors (i.e., family history, externalizing behaviors, gender, pubertal
      development, and age). RESULTS: Poorer baseline performance on tests of cognitive
      inhibition-interference predicted higher follow-up peak drinks on an occasion
      (beta = -.15; p < .001), more days of drinking (beta = -.15; p < .001), and more
      marijuana use days (beta = -.17; p < .001) by ages 17 to 18, above and beyond
      covariates. Performances on short-term memory, sustained attention, verbal
      learning and memory, visuospatial functioning, and spatial planning did not
      predict subsequent substance involvement (ps > .05). CONCLUSIONS: Compromised
      inhibitory functioning during early adolescence prior to the onset of substance
      use was related to more frequent and intense alcohol and marijuana use by late
      adolescence. Inhibition performance could help identify teens at risk for
      initiating heavy substance use during adolescence, and potentially could be
      modified to improve outcome.

PMID- 24749729
TI  - Long-term spacing effect benefits in developmental amnesia: case experiments in
      rehabilitation.
AB  - OBJECTIVE: The spacing effect describes the typical finding that repeated items
      are remembered best when additional items are introduced between each repetition
      than when the repetitions occur in immediate succession. In this study, we
      investigated the nature and limits of the spacing effect in the developmental
      amnesic case H.C. METHOD: In Experiment 1, we compared the performance of H.C. to
      that of controls on a short-term, free recall, verbal learning spacing paradigm
      while controlling for retention interval (timing of item review and recall). In
      Experiment 2, we compared the performance of H.C. to that of controls on a
      multiday, cued recall, verbal learning spacing paradigm, in which memory was
      assessed after 1 week. RESULTS: In both experiments, H.C. demonstrated a spacing
      effect comparable to the effect exhibited by controls. In Experiment 1, her final
      recall memory for long-lag (spaced) items was better than recall for no-lag
      (massed) items t(23) = 10.99, p < .001, d = 2.5. In Experiment 2, her final cued
      recall memory for next-day-reviewed (spaced) items was better than cued recall
      for same-day-reviewed (massed) items, t(20) = 17.6, p < .001, d = 4.1.
      CONCLUSIONS: This study demonstrates the spacing effect in a person with impaired
      episodic memory development and is the first to show long-term benefits of
      spacing in amnesia. Substantially slower learning-to-criterion suggests an
      alternate mechanism supporting the spacing effect, perhaps independent of the
      hippocampus. Spacing should be considered as a candidate memory intervention
      technique given its effectiveness in both short- and long-term learning settings.

PMID- 24749730
TI  - Allocentric but not egocentric orientation is impaired during normal aging: an
      ERP study.
AB  - OBJECTIVE: Behavioral studies of spatial navigation in aging indicate that
      orientation using an allocentric reference frame (object-centered orientation) is
      impaired, whereas orientation using egocentric processes (self-centered
      orientation) is not. It has been proposed that navigational deficits may result
      from more general alterations of perception and attention or executive functions.
      The purpose of this study is to assess allocentric and egocentric representation
      in elderly individuals, and to determine if age-related deficits in spatial
      navigation are related to an attentional decline. METHOD: We assessed encoding of
      the position of geometrical shapes, depending specifically on an allocentric or
      egocentric reference frame, during ERP recording in young and old subjects.
      RESULTS: Aging was associated with a performance decline in allocentric, but not
      egocentric, encoding. Both allocentric and egocentric conditions elicited
      parietal early components P1 and N1, reflecting top-down modulation, and
      components P2 and N2, reflecting selective attention and stimulus categorization.
      We observed age-associated effects on N1 and N2 amplitudes and on N2 latency in
      both spatial conditions. Moreover, impaired allocentric performance in older
      subjects was associated with a greater P2 amplitude and delayed P2 latency
      compared with younger subjects. CONCLUSION: These results suggest that elderly
      individuals present with deficits when spatial orientation relies on allocentric
      representation, and are associated with age-related deficits in spatial
      attention.

PMID- 24749731
TI  - Assessment of CALR mutations in myelofibrosis patients, post-allogeneic stem cell
      transplantation.

PMID- 24749732
TI  - Linking body mass and group dynamics in an obligate cooperative breeder.
AB  - Social and environmental factors influence key life-history processes and
      population dynamics by affecting fitness-related phenotypic traits such as body
      mass. The role of body mass is particularly pronounced in cooperative breeders
      due to variation in social status and consequent variation in access to
      resources. Investigating the mechanisms underlying variation in body mass and its
      demographic consequences can help elucidate how social and environmental factors
      affect the dynamics of cooperatively breeding populations. In this study, we
      present an analysis of the effect of individual variation in body mass on the
      temporal dynamics of group size and structure of a cooperatively breeding
      mongoose, the Kalahari meerkat, Suricata suricatta. First, we investigate how
      body mass interacts with social (dominance status and number of helpers) and
      environmental (rainfall and season) factors to influence key life-history
      processes (survival, growth, emigration and reproduction) in female meerkats.
      Next, using an individual-based population model, we show that the models
      explicitly including individual variation in body mass predict group dynamics
      better than those ignoring this morphological trait. Body mass influences group
      dynamics mainly through its effects on helper emigration and dominant
      reproduction. Rainfall has a trait-mediated, destabilizing effect on group
      dynamics, whereas the number of helpers has a direct and stabilizing effect.
      Counteracting effects of number of helpers on different demographic rates,
      despite generating temporal fluctuations, stabilizes group dynamics in the long
      term. Our study demonstrates that social and environmental factors interact to
      produce individual variation in body mass and accounting for this variation helps
      to explain group dynamics in this cooperatively breeding population. 

PMID- 24749733
TI  - The effect of fractal contact lenses on peripheral refraction in myopic model
      eyes.
AB  - PURPOSE: To test multizone contact lenses in model eyes: Fractal Contact Lenses
      (FCLs), designed to induce myopic peripheral refractive error (PRE). METHODS:
      Zemax ray-tracing software was employed to simulate myopic and accommodation
      dependent model eyes fitted with FCLs. PRE, defined in terms of mean sphere M and
      90 degrees -180 degrees  astigmatism J180, was computed at different peripheral
      positions, ranging from 0 to 35 degrees  in steps of 5 degrees , and for
      different pupil diameters (PDs). Simulated visual performance and changes in the
      PRE were also analyzed for contact lens decentration and model eye accommodation.
      For comparison purposes, the same simulations were performed with another
      commercially available contact lens designed for the same intended use: the Dual
      Focus (DF). RESULTS: PRE was greater with FCL than with DF when both designs were
      tested for a 3.5 mm PD, and with and without decentration of the lenses. However,
      PRE depended on PD with both multizone lenses, with a remarkable reduction of the
      myopic relative effect for a PD of 5.5 mm. The myopic PRE with contact lenses
      decreased as the myopic refractive error increased, but this could be compensated
      by increasing the power of treatment zones. A peripheral myopic shift was also
      induced by the FCLs in the accommodated model eye. In regard to visual
      performance, a myopia under-correction with reference to the circle of least
      confusion was obtained in all cases for a 5.5 mm PD. The ghost images, generated
      by treatment zones of FCL, were dimmer than the ones produced with DF lens of the
      same power. CONCLUSIONS: FCLs produce a peripheral myopic defocus without
      compromising central vision in photopic conditions. FCLs have several design
      parameters that can be varied to obtain optimum results: lens diameter, number of
      zones, addition and asphericity; resulting in a very promising customized lens
      for the treatment of myopia progression.

PMID- 24749734
TI  - The protein interacting with C-kinase (PICK1) interacts with and attenuates
      parkin-associated endothelial-like (PAEL) receptor-mediated cell death.
AB  - The parkin-associated endothelial-like receptor (PAELR, GPR37) is an orphan G
      protein-coupled receptor that interacts with and is degraded by parkin-mediated
      ubiquitination. Mutations in parkin are thought to result in PAELR accumulation
      and increase neuronal cell death in Parkinson's disease. In this study, we find
      that the protein interacting with C-kinase (PICK1) interacts with PAELR.
      Specifically, the Postsynaptic density protein-95/Discs large/ZO-1 (PDZ) domain
      of PICK1 interacted with the last three residues of the c-terminal (ct) located
      PDZ motif of PAELR. Pull-down assays indicated that recombinant and native PICK1,
      obtained from heterologous cells and rat brain tissue, respectively, were
      retained by a glutathione S-transferase fusion of ct-PAELR. Furthermore,
      coimmunoprecipitation studies isolated a PAELR-PICK1 complex from transiently
      transfected cells. PICK1 interacts with parkin and our data showed that PICK1
      reduces PAELR expression levels in transiently transfected heterologous cells
      compared to a PICK1 mutant that does not interact with PAELR. Finally, PICK1 over
      expression in HEK293 cells reduced cell death induced by PAEALR over-expression
      during rotenone treatment and these effects of PICK1 were attenuated during
      inhibition of the proteasome. These results suggest a role for PICK1 in
      preventing PAELR-induced cell toxicity.

PMID- 24749736
TI  - Isolation and structural characterization of a silver-platinum nanocluster,
      Ag4Pt2(DMSA)4.
AB  - We report the synthesis, isolation, and characterization of the ligand-protected
      bimetallic cluster, Ag4Pt2(DMSA)4 (DMSA = meso-2,3,-dimercaptosuccinic acid). The
      procedure is similar to the one employed for the synthesis of Ag4Ni2(DMSA)4.
      Theoretical studies suggest that the Pt and Ni atoms have square planar
      configurations. Because the crystal field splitting of 5d orbitals is typically
      larger than that for 3d orbitals, the Pt-based cluster has an optical spectrum
      that is significantly blue-shifted as compared to the Ni-based cluster. 

PMID- 24749735
TI  - Sterol partitioning by HMGR and DXR for routing intermediates toward withanolide
      biosynthesis.
AB  - Withanolides biosynthesis in the plant Withania somnifera (L.) Dunal is
      hypothesized to be diverged from sterol pathway at the level of 24-methylene
      cholesterol. The conversion and translocation of intermediates for sterols and
      withanolides are yet to be characterized in this plant. To understand the
      influence of mevalonate (MVA) and 2-C-methyl-d-erythritol-4-phosphate (MEP)
      pathways on sterols and withanolides biosynthesis in planta, we overexpressed the
      WsHMGR2 and WsDXR2 in tobacco, analyzed the effect of transient suppression
      through RNAi, inhibited MVA and MEP pathways and fed the leaf tissue with
      different sterols. Overexpression of WsHMGR2 increased cycloartenol, sitosterol,
      stigmasterol and campesterol compared to WsDXR2 transgene lines. Increase in
      cholesterol was, however, marginally higher in WsDXR2 transgenic lines. This was
      further validated through transient suppression analysis, and pathway inhibition
      where cholesterol reduction was found higher due to WsDXR2 suppression and all
      other sterols were affected predominantly by WsHMGR2 suppression in leaf. The
      transcript abundance and enzyme analysis data also correlate with sterol
      accumulation. Cholesterol feeding did not increase the withanolide content
      compared to cycloartenol, sitosterol, stigmasterol and campesterol. Hence, a
      preferential translocation of carbon from MVA and MEP pathways was found
      differentiating the sterols types. Overall results suggested that MVA pathway was
      predominant in contributing intermediates for withanolides synthesis mainly
      through the campesterol/stigmasterol route in planta. 

PMID- 24749737
TI  - Characterization and stability study of polysorbate 20 in therapeutic monoclonal
      antibody formulation by multidimensional ultrahigh-performance liquid
      chromatography-charged aerosol detection-mass spectrometry.
AB  - Polysorbate 20 is a nonionic surfactant commonly used in the formulation of
      therapeutic monoclonal antibodies (mAb) to prevent protein denaturation and
      aggregation. It is critical to understand the molecular heterogeneity and
      stability of polysorbate 20 in mAb formulations as polysorbate can gradually
      degrade in aqueous solution over time by multiple pathways losing surfactant
      functions and leading to protein aggregation. The molecular heterogeneity of
      polysorbate and the interference from proteins and the excipient in the
      formulation matrix make it a challenge to study polysorbate in protein
      formulations. In this work, the characterization and stability study of
      polysorbate 20 in the presence of mAb formulation sample matrix is first reported
      using two-dimensional liquid chromatography (2DLC) coupled with charged aerosol
      detection (CAD) and mass spectrometry (MS) detection. A mixed-mode column that
      has both anion-exchange and reversed-phase properties was used in the first
      dimension to separate protein and polysorbate in the formulation sample, while
      polysorbate 20 esters were trapped online and then analyzed using an reversed
      phase ultrahigh-performance liquid chromatography (RP-UHPLC) column in the second
      dimension to further separate the ester species. The MS served as the third
      dimension to further resolve as well as to identify the polysorbate ester
      subspecies. Another 2DLC method using a cation-exchange column in the first
      dimension and the same RP-UHPLC method in the second dimension was developed to
      analyze the degradation products of polysorbate 20. Stability samples of a
      protein drug product were studied using these two 2DLC-CAD-MS methods to
      separate, identify, and quantify the multiple ester species in polysorbate 20 and
      also to monitor the change of their corresponding degradants. We found different
      polysorbate esters degrade at different rates, and importantly, the degradation
      rates for some esters are different in the protein formulation compared to a
      placebo that has no protein. The multidimensional UHPLC-CAD-MS approach provides
      insights into the heterogeneous stability behaviors of polysorbate 20 subspecies
      in real-time stability samples of a mAb formulation. 

PMID- 24749738
TI  - Intravesical treatment of bladder pain syndrome/interstitial cystitis: from the
      conventional regimens to the novel botulinum toxin injections.
AB  - INTRODUCTION: Bladder pain syndrome (BPS) includes interstitial cystitis (IC) and
      is often used as a synonym of it (i.e., BPS/IC). It is associated with lower
      urinary tract symptoms as well as with negative cognitive, behavioral, sexual
      and/or emotional consequences. Unfortunately, none of the numerous existing oral
      and intravesical treatments have been effective for all of the BPS subtypes and
      therefore relevant research is ongoing. AREAS COVERED: In this review, the
      authors analyze the existing literature for the intravesical treatment of BPS/IC
      with focus on the novel administration of botulinum toxin (BTX). Several
      intravesical drugs have been studied in the past, including lidocaine, heparin,
      pentosan polysulfate sodium, dimethyl sulfoxide, chondroitin sulfate, hyaluronic
      acid as well as investigational drugs such as GM-0111. Recently, intravesical
      submucosal injections of BTX have been studied in patients with BPS/IC. EXPERT
      OPINION: Most of the recent studies use BTX-A with no serious adverse effects and
      with satisfactory results in patients who do not respond to oral or standard
      intravesical therapy. Nevertheless, there is no consensus regarding the best
      dosage scheme of BTX, the injection sites and the treatment intervals. BTX
      intravesical administration in patients with BPS/IC is a safe and efficient
      treatment option; yet the level of evidence of the initial studies is not high.
      There is still the need for large randomized controlled studies so that a
      consensus can be reached for the ideal BTX dosage, injection sites and intervals
      between treatments.

PMID- 24749739
TI  - The nature of professional and relational self-aspects at the goal and narrative
      levels of personality.
AB  - The self-concept is constituted by a series of context-specific self-aspects.
      Researchers have considered the manner in which personality traits vary across
      these self-aspects. Here, we examined self-aspects corresponding to professional
      and relational contexts at the goal and narrative levels of personality. In each
      of two studies, participants provided lists of goals and recounted self-defining
      narratives, corresponding to the aforementioned contexts. Goals and narratives
      were coded for themes of agency and communion. At both descriptive levels, agency
      more characterized the professional self-aspect and communion, the relational
      self-aspect. A consideration of context-specific goals and narratives informs
      understanding regarding the nature of the self in its multifaceted form. 

PMID- 24749740
TI  - Pediatric residents' perspectives on relationships with other professionals
      during well child care.
AB  - This study aimed to examine pediatric residents' perspectives of primary care
      professional relationships. Using a longitudinal qualitative study design, we
      conducted 15 semi-structured interviews with five second-year pediatric residents
      who elected to participate in a one-year intervention, facilitating group well
      child care (GWCC). Pediatric residents described a spectrum of professional
      relationship types including: ignorant, transactional, workaround, educational
      and equitable. Residents described ignorant, transactional and workaround
      relationships with feelings of frustration, and they described educational and
      equitable relationships with feelings of satisfaction and humility. While
      residents described optimal relationships in both traditional WCC and GWCC, they
      described suboptimal relationships in only traditional WCC. Further study is
      needed to assess if our model of GWCC may create a scaffolding upon which optimal
      relationships in interprofessional teams are likely to flourish.

PMID- 24749742
TI  - The student-run free clinic: an ideal site to teach interprofessional education?
AB  - Student-run free clinics (SRFCs) often include an interprofessional group of
      health professions students and preceptors working together toward the common
      goal of caring for underserved populations. Therefore, it would seem that these
      clinics would be an ideal place for students to participate in an
      interprofessional collaborative practice and for interprofessional education to
      occur. This article describes a prospective, observational cohort study of
      interprofessional attitudes and skills including communication and teamwork
      skills and attitudes about interprofessional learning, relationships and
      interactions of student volunteers in a SRFC compared to students who applied and
      were not accepted to the clinic and to students who never applied to the clinic.
      This study showed a decrease in attitudes and skills after the first year for all
      groups. Over the next two years, the total score on the survey for the accepted
      students was higher than the not accepted students. The students who were not
      accepted also became more similar to students who never applied. This suggests a
      protective effect against declining interprofessional attitudes and skills for
      the student volunteers in a SRFC. These findings are likely a function of the
      design of the clinical and educational experience in the clinic and of the length
      of contact the students have with other professions.

PMID- 24749744
TI  - In memoriam Maria Musarella.

PMID- 24749745
TI  - An unbiased method to build benchmarking sets for ligand-based virtual screening
      and its application to GPCRs.
AB  - Benchmarking data sets have become common in recent years for the purpose of
      virtual screening, though the main focus had been placed on the structure-based
      virtual screening (SBVS) approaches. Due to the lack of crystal structures, there
      is great need for unbiased benchmarking sets to evaluate various ligand-based
      virtual screening (LBVS) methods for important drug targets such as G protein
      coupled receptors (GPCRs). To date these ready-to-apply data sets for LBVS are
      fairly limited, and the direct usage of benchmarking sets designed for SBVS could
      bring the biases to the evaluation of LBVS. Herein, we propose an unbiased method
      to build benchmarking sets for LBVS and validate it on a multitude of GPCRs
      targets. To be more specific, our methods can (1) ensure chemical diversity of
      ligands, (2) maintain the physicochemical similarity between ligands and decoys,
      (3) make the decoys dissimilar in chemical topology to all ligands to avoid false
      negatives, and (4) maximize spatial random distribution of ligands and decoys. We
      evaluated the quality of our Unbiased Ligand Set (ULS) and Unbiased Decoy Set
      (UDS) using three common LBVS approaches, with Leave-One-Out (LOO) Cross
      Validation (CV) and a metric of average AUC of the ROC curves. Our method has
      greatly reduced the "artificial enrichment" and "analogue bias" of a published
      GPCRs benchmarking set, i.e., GPCR Ligand Library (GLL)/GPCR Decoy Database
      (GDD). In addition, we addressed an important issue about the ratio of decoys per
      ligand and found that for a range of 30 to 100 it does not affect the quality of
      the benchmarking set, so we kept the original ratio of 39 from the GLL/GDD. 

PMID- 24749747
TI  - Parasitic castration promotes coevolutionary cycling but also imposes a cost on
      sex.
AB  - Antagonistic coevolution between hosts and parasites is thought to drive a range
      of biological phenomena including the maintenance of sexual reproduction. Of
      particular interest are conditions that produce persistent fluctuations in the
      frequencies of genes governing host-parasite specificity (coevolutionary
      cycling), as sex may be more beneficial than asexual reproduction in a constantly
      changing environment. Although many studies have shown that coevolutionary
      cycling can lead to the maintenance of sex, the effects of ecological feedbacks
      on the persistence of these fluctuations in gene frequencies are not well
      understood. Here, we use a simple deterministic model that incorporates
      ecological feedbacks to explore how parasitic reductions in host fecundity affect
      the maintenance of coevolutionary cycling. We demonstrate that parasitic
      castration is inherently destabilizing and may be necessary for coevolutionary
      cycling to persist indefinitely, but also reduces the likelihood that sexually
      reproducing individuals will find a fertile partner, which may select against
      sex. These findings suggest that castrators can play an important role in shaping
      host evolution and are likely to be good targets for observing fluctuations in
      gene frequencies that govern specificity in host-parasite interactions. 

PMID- 24749746
TI  - Human CD4+ CD39+ regulatory T cells produce adenosine upon co-expression of
      surface CD73 or contact with CD73+ exosomes or CD73+ cells.
AB  - While murine CD4(+) CD39(+) regulatory T cells (T(reg)) co-express CD73 and
      hydrolyze exogenous (e) adenosine triphosphate (ATP) to immunosuppressive
      adenosine (ADO), surface co-expression of CD73 on human circulating CD4(+)
      CD39(+) T(reg) is rare. Therefore, the ability of human T(reg) to produce and
      utilize ADO for suppression remains unclear. Using mass spectrometry, we measured
      nucleoside production by subsets of human CD4(+) CD39(+) and CD4(+) CD39(
      )CD73(+) T cells or CD19(+) B cells isolated from blood of 30 volunteers and 14
      cancer patients. CD39 and CD73 expression was evaluated by flow cytometry,
      Western blots, confocal microscopy or reverse transcription-polymerase chain
      reaction (RT-PCR). Circulating CD4(+) CD39(+) T(reg) which hydrolyzed eATP to 5'
      AMP contained few intracytoplasmic granules and had low CD73 mRNA levels. Only
      ~1% of these T(reg) were CD39(+) CD73(+) . In contrast, CD4(+) CD39(neg) CD73(+)
      T cells contained numerous CD73(+) granules in the cytoplasm and strongly
      expressed surface CD73. In vitro-generated T(reg) (Tr1) and most B cells were
      CD39(+) CD73(+) . All these CD73(+) T cell subsets and B cells hydrolyzed 5'-AMP
      to ADO. Exosomes isolated from plasma of normal control (NC) or cancer patients
      carried enzymatically active CD39 and CD73(+) and, when supplied with eATP,
      hydrolyzed it to ADO. Only CD4(+) CD39(+) T(reg) co-incubated with CD4(+) CD73(+)
      T cells, B cells or CD39(+) CD73(+) exosomes produced ADO. Thus, contact with
      membrane-tethered CD73 was sufficient for ADO production by CD4(+) CD39(+)
      T(reg). In microenvironments containing CD4(+) CD73(+) T cells, B cells or
      CD39(+) CD73(+) exosomes, CD73 is readily available to CD4(+) CD39(+) CD73(neg)
      T(reg) for the production of immunosuppressive ADO.

PMID- 24749748
TI  - Changes following premarital education for couples with differing degrees of
      future marital risk.
AB  - The present study explored changes in individuals' relationship cognitions and
      behaviors following premarital education for couples with different risk
      profiles. The sample consisted of 63 couples who completed the PREPARE program
      and were classified for future marital risk based on dyadic information. A
      significant interaction effect was found between risk and time, with individuals
      in relationships classified as high risk exhibiting greater change at 4 weeks
      postprogram compared to low-risk individuals. Perceived helpfulness of topics
      also varied by couple type. Findings provide support for adapting premarital
      education programs for high-risk couples and offer clinicians and educators
      specific insights for areas of emphasis when working with different types of
      couples. 

PMID- 24749749
TI  - Lymphomatoid papulosis in children: a series of 25 cases.
AB  - BACKGROUND: Lymphomatoid papulosis (LyP) is an uncommon cutaneous T-cell
      lymphoproliferative disorder (CTLPD) rarely encountered in children. OBJECTIVES:
      To specify characteristics of paediatric LyP and to describe both diagnostic
      difficulties and the course of the disease with the experience of 10 years'
      follow-up. METHODS: This was a retrospective, single-centre study of 25 children
      diagnosed with LyP according to the 2008 World Health Organization guidelines,
      and a clinical and pathological correlation by two experts. RESULTS: The mean age
      at onset was 7.5 years. The lesions were mostly papulonodular with frequent
      pruritus (40%). Mucosal involvement was sometimes observed. A single ulcerative
      nodule was initially suggestive of a primary cutaneous anaplastic large-cell
      lymphoma (C-ALCL). Pityriasis lichenoides was associated in 36% of cases, atopic
      dermatitis in 28% and nonspecific infections in 28%. Complete remission was
      observed in 44% of cases. Through the mean follow-up of 10 years, none of our
      patients have experienced lymphoma occurrence. Histopathological subtype A
      clearly predominated (82%). A marked eosinophilic infiltrate was present in 44%
      of cases and a cutaneous T-gamma clone in 40%. No correlation was observed
      between histopathological subtype, cutaneous clone or LyP clinical course.
      CONCLUSIONS: Paediatric LyP belongs to the group of CD30-positive CTLPDs
      including C-ALCL. Children have to be carefully followed up lifelong, even if the
      prognosis appears good. The high frequencies of an associated viral infection,
      atopic dermatitis, marked eosinophilic infiltrate and a good outcome suggest that
      paediatric LyP could be considered a reactional disease rather than a malignant
      disorder.

PMID- 24749750
TI  - Factor analysis of the Achievement of Therapeutic Objectives Scale (ATOS) in
      short-term dynamic psychotherapy and cognitive therapy.
AB  - This study examined the factor structure of the Achievement of Therapeutic
      Objectives Scale (ATOS; McCullough, Larsen, et al., 2003) in short-term dynamic
      psychotherapy (STDP) and cognitive therapy (CT). The ATOS is a process scale that
      has shown promise as a measure of patients' achievements of treatment objectives
      in STDP and CT and is conceptualized as comprising 7 subscales hypothesized to
      cluster according to 3 main treatment objectives (defense restructuring, affect
      restructuring, and restructuring of sense of self and others). However, the
      factor structure of the ATOS has not been examined empirically previously. Data
      were derived from ratings of videotaped therapy sessions from a randomized
      controlled trial, comparing STDP and CT for patients with Cluster C personality
      disorders. The model fit of a 2- and 3-factor solution was examined in the
      combined patient sample, as well as in each treatment separately, utilizing
      structural equation modeling. Both a 2- and 3-factor model provided acceptable
      fit to the data. The results add to the psychometric soundness of the ATOS as an
      innovative observer-based instrument for examining process in STDP and CT.

PMID- 24749751
TI  - Feasibility of text messaging for ecological momentary assessment of marijuana
      use in college students.
AB  - Measuring self-reported substance use behavior is challenging due to issues
      related to memory recall and patterns of bias in estimating behavior. Limited
      research has focused on the use of ecological momentary assessment (EMA) to
      evaluate marijuana use. This study assessed the feasibility of using short
      message service (SMS) texting as a method of EMA with college-age marijuana
      users. Our goals were to evaluate overall response/compliance rates and trends of
      data missingness, response time, baseline measures (e.g., problematic use)
      associated with compliance rates and response times, and differences between EMA
      responses of marijuana use compared to timeline followback (TLFB) recall. Nine
      questions were texted to participants on their personal cell phones 3 times a day
      over a 2-week period. Overall response rate was high (89%). When examining
      predictors of the probability of data missingness with a hierarchical logistic
      regression model, we found evidence of a higher propensity for missingness for
      Week 2 of the study compared to Week 1. Self-regulated learning was significantly
      associated with an increase in mean response time. A model fit at the participant
      level to explore response time found that more time spent smoking marijuana
      related to higher response times, while more time spent studying and greater "in
      the moment" academic motivation and craving were associated with lower response
      times. Significant differences were found between the TLFB and EMA, with greater
      reports of marijuana use reported through EMA. Overall, results support the
      feasibility of using SMS text messaging as an EMA method for college-age
      marijuana users.

PMID- 24749752
TI  - Rural parents' perceived stigma of seeking mental health services for their
      children: development and evaluation of a new instrument.
AB  - The purpose of our research was to examine the validity of score interpretations
      of an instrument developed to measure parents' perceptions of stigma about
      seeking mental health services for their children. The validity of the score
      interpretations of the instrument was tested in 2 studies. Study 1 employed
      confirmatory factor analysis (CFA), using a split half approach, and construct
      and criterion validity on data from the entire sample of parents in rural
      Appalachia whose children were experiencing psychosocial concerns (N = 347),
      while Study 2 employed CFA, construct and criterion validity, and predictive
      validity of the scores on data from a general sample of parents in rural
      Appalachia (N = 184). Results of exploratory and confirmatory factor analyses
      revealed support for a 2-factor model of parents' perceived stigma, which
      represented both self and public forms of stigma associated with seeking mental
      health services for their children, and correlated with existing measures of
      stigma and other psychosocial variables. Further, the new self and public stigma
      scale significantly predicted parents' willingness to seek services for children.

PMID- 24749753
TI  - Diagnostic reliability of MMPI-2 computer-based test interpretations.
AB  - Reflecting the common use of the MMPI-2 to provide diagnostic considerations,
      computer-based test interpretations (CBTIs) also typically offer diagnostic
      suggestions. However, these diagnostic suggestions can sometimes be shown to vary
      widely across different CBTI programs even for identical MMPI-2 profiles. The
      present study evaluated the diagnostic reliability of 6 commercially available
      CBTIs using a 20-item Q-sort task developed for this study. Four raters each
      sorted diagnostic classifications based on these 6 CBTI reports for 20 MMPI-2
      profiles. Two questions were addressed. First, do users of CBTIs understand the
      diagnostic information contained within the reports similarly? Overall,
      diagnostic sorts of the CBTIs showed moderate inter-interpreter diagnostic
      reliability (mean r = .56), with sorts for the 1/2/3 profile showing the highest
      inter-interpreter diagnostic reliability (mean r = .67). Second, do different
      CBTIs programs vary with respect to diagnostic suggestions? It was found that
      diagnostic sorts of the CBTIs had a mean inter-CBTI diagnostic reliability of r =
      .56, indicating moderate but not strong agreement across CBTIs in terms of
      diagnostic suggestions. The strongest inter-CBTI diagnostic agreement was found
      for sorts of the 1/2/3 profile CBTIs (mean r = .71). Limitations and future
      directions are discussed.

PMID- 24749754
TI  - Assessment of nonsuicidal self-injury: development and initial validation of the
      Non-Suicidal Self-Injury-Assessment Tool (NSSI-AT).
AB  - Research tools for assessing nonsuicidal self-injury (NSSI) epidemiology in
      community populations are few and are either limited in the scope of NSSI
      characteristics assessed or included as part of suicide assessment. Though these
      surveys have been immensely useful in establishing the presence of NSSI and in
      documenting basic epidemiological characteristics, they have been less useful in
      describing secondary NSSI features such as NSSI context, habituation, or
      perceived life impact. The aim of the current study was to examine the
      reliability of the test scores and validity of test score interpretations in a
      university population for the Non-Suicidal Self-Injury-Assessment Tool (NSSI-AT),
      a web-based measure of NSSI designed to assess primary (such as form, frequency,
      and function) and secondary (including but not limited to NSSI habituation;
      contexts in which NSSI is practiced; and NSSI perceived life interference,
      treatment, and impacts) NSSI characteristics for research purposes. Data for
      these analyses were drawn from 3 samples, all of which were originally part of a
      2007 study of randomly selected students from 8 northeast and midwest public and
      private universities that participated in a web-based study entitled the Survey
      of Student Wellbeing. Overall, results provide support for the reliability of
      NSSI-AT test scores (as assessed by test-retest) and validity of NSSI-AT test
      score interpretations for the behavior and frequency modules (as assessed using
      concurrent, convergent, and discriminant evidence) in this population.
      Implications for research as well as next steps are discussed.

PMID- 24749755
TI  - Validity of the Short Mood and Feelings Questionnaire in late adolescence.
AB  - Studies examining the validity of the Short Mood and Feelings Questionnaire
      (SMFQ; Angold, Costello, & Messer, 1995) have largely focused on selected or
      clinical samples in childhood (6-11 years) or early to midadolescence (12-16
      years) and have not investigated misclassifications or how the SMFQ relates to
      adult depression measures. Using data from the Avon Longitudinal Study of Parents
      and Children (2012), we assessed the validity of the SMFQ in relation to an adult
      depression measure administered in late adolescence (age 17-18 years). We also
      investigated sociodemographic and clinical variables previously shown to affect
      misclassification on short self-administered questionnaires compared with more
      detailed assessments of depression. We assessed construct validity using factor
      and item response theory analysis. To investigate content validity, we tabulated
      SMFQ items against the International Classification of Diseases (ICD-10; World
      Health Organization, 1992) and Diagnostic and Statistical Manual of Mental
      Disorders (4th ed.; American Psychiatric Association, 1994) depressive symptoms.
      Criterion validity was examined using receiver operating characteristic (ROC)
      analysis. Potential misclassifications were investigated using logistic
      regression and multiple-indicator multiple-cause modeling. Factor analysis
      produced high loadings, low residual variances, and appropriate model fit
      indices. Seven of the 10 ICD-10 depressive symptoms were covered by at least 1
      SMFQ item. The discriminatory ability of the SMFQ for meeting ICD-10 diagnostic
      criteria for depression was very high (area under ROC curve = 0.90). Individuals
      with anxiety symptoms, females, and less well-educated individuals overreported
      depressive symptoms on the SMFQ in relation to ICD-10 depression. We conclude the
      SMFQ is a valid instrument capturing a latent trait of depression in a community
      based sample in late adolescence. Further work should be carried out to increase
      understanding of variables associated with misclassification.

PMID- 24749756
TI  - Examining the latent structure of anxiety sensitivity in adolescents using factor
      mixture modeling.
AB  - Anxiety sensitivity has been implicated as an important risk factor,
      generalizable to most anxiety disorders. In adults, factor mixture modeling has
      been used to demonstrate that anxiety sensitivity is best conceptualized as
      categorical between individuals. That is, whereas most adults appear to possess
      normative levels of anxiety sensitivity, a small subset of the population appears
      to possess abnormally high levels of anxiety sensitivity. Further, those in the
      high anxiety sensitivity group are at increased risk of having high levels of
      anxiety and of having an anxiety disorder. This study was designed to determine
      whether these findings extend to adolescents. Factor mixture modeling was used to
      examine the best fitting model of anxiety sensitivity in a sample of 277
      adolescents (M age = 11.0 years, SD = 0.81). Consistent with research in adults,
      the best fitting model consisted of 2 classes, 1 containing adolescents with high
      levels of anxiety sensitivity (n = 25) and another containing adolescents with
      normative levels of anxiety sensitivity (n = 252). Examination of anxiety
      sensitivity subscales revealed that the social concerns subscale was not
      important for classification of individuals. Convergent and discriminant validity
      of anxiety sensitivity classes were found in that membership in the high anxiety
      sensitivity class was associated with higher mean levels of anxiety symptoms,
      controlling for depression and externalizing problems, and was not associated
      with higher mean levels of depression or externalizing symptoms controlling for
      anxiety problems.

PMID- 24749758
TI  - Little peaks with big effects: establishing the role of minor plant volatiles in
      plant-insect interactions.
AB  - Plants emit complex mixtures of volatile organic compounds from floral and
      vegetative tissue, especially after herbivore damage, so it is difficult to
      associate individual compounds with activity towards pollinators, herbivores or
      herbivore enemies. Attention has usually focused upon the biological activity of
      the most abundant compounds; but here, we detail a number of reports implicating
      minor volatiles in attractant or deterrent roles. This is not surprising given
      the exquisite sensitivity of insect olfactory systems for certain substances. In
      this context, it is worth reconsidering the methods involved in sampling volatile
      compounds from plants, measuring their abundance and determining their biological
      activity to ensure that minor compounds are not overlooked. Here, we describe
      various experimental approaches and chemical and statistical methods that should
      increase the chance of detecting minor compounds with major biological
      activities. 

PMID- 24749757
TI  - Outpatient bendamustine and idarubicin for upfront therapy of elderly acute
      myeloid leukaemia/myelodysplastic syndrome: a phase I/II study using an
      innovative statistical design.
AB  - Combinations of agents may improve outcomes among elderly acute myeloid leukaemia
      (AML) and high-risk myelodysplastic syndrome (MDS) patients. We performed an
      adaptive phase I/II trial for newly-diagnosed AML or high-risk MDS patients aged
      >=50 years using a Bayesian approach to determine whether 1 of 3 doses of
      bendamustine (45, 60, 75 mg/m(2) days 1-3), together with idarubicin (12 mg/m(2)
      days 1-2), might provide a complete response (CR) rate >=40% with <30% grade 3-4
      non-haematological toxicity. We treated 39 patients (34 AML; five MDS with >10%
      marrow blasts; median age 73 years). None of the three bendamustine doses in
      combination with idarubicin met the required CR and toxicity rates; the 75
      mg/m(2) dose because of excess toxicity (two of three patients) and the 60
      mg/m(2) dose because of low efficacy (CR rate 10/33), although no grade 3-4 non
      haematological toxicity was seen at this dose. Median survival was 7.2 months.
      All patients began treatment as outpatients but hospitalization was required in
      90% (35/39). Although we did not find a dose of bendamustine combined with
      idarubicin that would provide a CR rate of >40% with acceptable toxicity,
      bendamustine may have activity in AML/MDS patients, suggesting its addition to
      other regimens may be warranted.

PMID- 24749759
TI  - Enteric GFAP expression and phosphorylation in Parkinson's disease.
AB  - Enteric glial cells (EGCs) are in many respects similar to astrocytes of the
      central nervous system and express similar proteins including glial fibrillary
      acidic protein (GFAP). Changes in GFAP expression and/or phosphorylation have
      been reported during brain damage or central nervous system degeneration. As in
      Parkinson's disease (PD) the enteric neurons accumulate alpha-synuclein, and thus
      are showing PD-specific pathological features, we undertook the present survey to
      study whether the enteric glia in PD become reactive by assessing the expression
      and phosphorylation levels of GFAP in colonic biopsies. Twenty-four PD, six
      progressive supranuclear palsy (PSP), six multiple system atrophy (MSA) patients,
      and 21 age-matched healthy controls were included. The expression levels and the
      phosphorylation state of GFAP were analyzed in colonic biopsies by western blot.
      Additional experiments were performed using real-time PCR for a more precise
      analysis of the GFAP isoforms expressed by EGCs. We showed that GFAPkappa was the
      main isoform expressed in EGCs. As compared to control subjects, patients with
      PD, but not PSP and MSA, had significant higher GFAP expression levels in their
      colonic biopsies. The phosphorylation level of GFAP at serine 13 was
      significantly lower in PD patients compared to control subjects. By contrast, no
      change in GFAP phosphorylation was observed between PSP, MSA and controls. Our
      findings provide evidence that enteric glial reaction occurs in PD and further
      reinforce the role of the enteric nervous system in the initiation and/or the
      progression of the disease. We showed that GFAP is over-expressed and
      hypophosphorylated in the enteric glial cells (EGCs) of Parkinson's disease (PD)
      patients as compared to healthy subjects and patients with atypical parkinsonism
      (MSA, multiple system atrophy and PSP, progressive supranuclear palsy). Our
      findings provide evidence that enteric glial reaction occurs in PD but not in PSP
      and MSA and further reinforce the role of the enteric nervous system in the
      pathophysiology of PD. 

PMID- 24749761
TI  - Licensed nurse staffing and health service availability in residential care and
      assisted living.
AB  - OBJECTIVES: To create data-driven typologies of licensed nurse staffing and
      health services in residential care and assisted living (RC/AL). DESIGN: Cluster
      analysis was used to describe the patterns of licensed nurse staffing and 47
      services and the extent to which these clusters were related. SETTING: RC/AL
      communities in the United States. PARTICIPANTS: A convenience sample of
      administrators and healthcare supervisors from 89 RC/AL communities in 22 states.
      MEASUREMENT: RC/AL characteristics, licensed nurse staffing (total number of
      hours that registered nurses (RNs) and licensed practical nurses (LPNs) worked),
      number of hours that contract nurses worked, and availability of 47 services.
      RESULTS: Analysis revealed four licensed nurse staffing clusters defined
      according to total number of hours and the type of nurse providing the hours (RN,
      LPN, or a mix of both). They ranged from no or minimal RN and LPN hours to high
      nursing hours with a mix of RNs and LPNs. The 47 services clustered into five
      clusters: basic services; technically complex services; assessments, wound care,
      and therapies; testing and specialty services; and gastrostomy and intravenous
      medications. The availability of services was related to the presence of nurses
      (RNs and LPNs) except for the gastrostomy and intravenous medication services,
      which were not readily available. CONCLUSION: The amount and skill mix of
      licensed nurse staffing varies in RC/AL and is related to the types of services
      available. These findings may have implications for resident care and outcomes.
      Future work in this area, including extension to include nonnurse direct care
      workers, is needed.

PMID- 24749760
TI  - Motor impulsivity in Parkinson disease: associations with COMT and DRD2
      polymorphisms.
AB  - Parkinson disease (PD) is an age-related degenerative disease of the brain,
      characterized by motor, cognitive, and psychiatric symptoms. Neurologists and
      neuroscientists now understand that several symptoms of the disease, including
      hallucinations and impulse control behaviors, stem from the dopaminergic
      medications used to control the motor aspects of PD. Converging evidence from
      animals and humans suggests that individual differences in the genes that affect
      the dopamine system influence the response of PD patients to dopaminergic
      medication. In this study, we tested the hypothesis that patients taking dopamine
      replacement therapy who carry candidate alleles that increase dopamine signaling,
      exhibit greater amounts of motor impulsivity. We examined the relation between
      inhibitory ability (measured by the Stop Signal Task) and polymorphisms of COMT
      Val158Met and DRD2 C957T in patients with idiopathic PD. On the Stop Signal Task,
      carriers of COMT Val/Met and Met/Met genotypes were more impulsive than Val/Val
      carriers, but we did not find a link between DRD2 polymorphisms and inhibitory
      ability. These results support the hypothesis that the Met allele of COMT confers
      an increased risk for behavioral impulsivity in PD patients, whereas DRD2
      polymorphisms appear to be less important in determining whether PD patients
      exhibit a dopamine overdose in the form of motor impulsivity. 

PMID- 24749762
TI  - White paper on how to go forward with cell-based advanced therapies in Europe.
AB  - The current White paper summarizes the discussions and exchange of experiences
      during the first European Interdisciplinary Summit on Cell-Based ATMPs held in
      Vienna, Austria, May 02-03, 2013. The meeting was supported by the Research
      Networking Programme REMEDIC (regenerative medicine) funded by the European
      Science Foundation and by the British Medical Research Council. To improve the
      competitiveness of Europe in the field of cell-based Advanced Medicinal Therapy
      Products (ATMPs), the following key issues were identified during the meeting:
      removal of national hurdles in the European Union, harmonization of national and
      subnational differences in Hospital Exemption rules, improved treatment
      algorithms for reimbursement, better knowledge on the mode of action, predictive
      preclinical efficacy and safety testing, need for innovative systems for
      preclinical testing, appropriate product characterization, manufacturing with
      cost of goods in mind, and appropriate design of clinical trials. 

PMID- 24749763
TI  - Systematic review with network meta-analysis: the efficacy of anti-TNF agents for
      the treatment of Crohn's disease.
AB  - BACKGROUND: Anti-tumour necrosis factor-alpha agents (anti-TNF) are effective
      therapies for the treatment of Crohn's disease (CD), but their comparative
      efficacy is unknown. AIM: To perform a network meta-analysis comparing the
      efficacy of anti-TNF therapies in CD. METHODS: After screening 506 studies,
      reviewers extracted information on 10 studies. Traditional meta-analysis (TMA)
      was used to compare each anti-TNF agent to placebo. Bayesian network meta
      analysis (NMA) was performed to compare the effects of anti-TNF agents to
      placebo. In addition, sample sizes for comparative efficacy trials were
      calculated. RESULTS: Compared to placebo, TMA revealed that anti-TNF agents
      result in a higher likelihood of induction of remission and response (RR: 1.66,
      95% CI: 1.17-2.36 and RR: 1.43, 95% CI: 1.17-1.73, respectively) as well as
      maintenance of remission and response (RR: 1.78, 95% CI: 1.51-2.09 and RR: 1.68,
      95% CI: 1.46-1.93, respectively). NMA found nonsignificant trends between
      infliximab and adalimumab or certolizumab pegol. Among subcutaneous therapies,
      NMA demonstrated superiority of adalimumab to certolizumab pegol for induction of
      remission (RR: 2.93, 95% CrI: 1.21-7.75). Sample size calculations suggest that
      adequately powered head-to-head comparative efficacy trials would require greater
      than 3000 patients. CONCLUSIONS: All anti-TNF agents are effective for induction
      and maintenance of response and remission in the treatment of CD. Although
      adalimumab is superior to certolizumab pegol for induction of remission, there is
      no evidence of clinical superiority among anti-TNF agents. Head-to-head trials
      among the anti-TNF agents are impractical in terms of size and cost.

PMID- 24749764
TI  - Cold plasma rapid decontamination of food contact surfaces contaminated with
      Salmonella biofilms.
AB  - Cross-contamination of foods from persistent pathogen reservoirs is a known risk
      factor in processing environments. Industry requires a rapid, waterless, zero
      contact, chemical-free method for removing pathogens from food contact surfaces.
      Cold plasma was tested for its ability to inactivate Salmonella biofilms. A 3
      strain Salmonella culture was grown to form adherent biofilms for 24, 48, or 72 h
      on a test surface (glass slides). These were placed on a conveyor belt and passed
      at various line speeds to provide exposure times of 5, 10, or 15 s. The test
      plate was either 5 or 7.5 cm under a plasma jet emitter operating at 1 atm using
      filtered air as the feed gas. The frequency of high-voltage electricity was
      varied from 23 to 48 kHz. At the closer spacing (5 cm), cold plasma reduced
      Salmonella biofilms by up to 1.57 log CFU/mL (5 s), 1.82 log CFU/mL (10 s), and
      2.13 log CFU/mL (15 s). Increasing the distance to 7.5 cm generally reduced the
      efficacy of the 15 s treatment, but had variable effects on the 5 and 10 s
      treatments. Variation of the high-voltage electricity had a greater effect on 10
      and 15 s treatments, particularly at the 7.5 cm spacing. For each combination of
      time, distance, and frequency, Salmonella biofilms of 24, 48, and 72 h growth
      responded consistently with each other. The results show that short treatments
      with cold plasma yielded up to a 2.13 log reduction of a durable form of
      Salmonella contamination on a model food contact surface. This technology shows
      promise as a possible tool for rapid disinfection of materials associated with
      food processing. PRACTICAL APPLICATION: Pathogens such as Salmonella can form
      chemical-resistant biofilms, making them difficult to remove from food contact
      surfaces. A 15 s treatment with cold plasma reduced mature Salmonella biofilms by
      up to 2.13 log CFU/mL (99.3%). This contact-free, waterless method uses no
      chemical sanitizers. Cold plasma may therefore have a practical application for
      conveyor belts, equipment, and other food contact surfaces where a rapid, dry
      antimicrobial process is required.

PMID- 24749765
TI  - Antiapoptotic effects of anthocyanin from the seed coat of black soybean against
      oxidative damage of human lens epithelial cell induced by H2O2.
AB  - PURPOSE: To describe the protective effect of anthocyanin from black soybean in
      human lens epithelial cell line (HLE-B3) under H2O2-induced oxidative stress.
      METHODS: Cytotoxicity of anthocyanin and H2O2 were determined by Cell Counting
      Kit-8 test. Viability of HLE-B3 cells under various H2O2 concentration (0, 50 and
      100 MUM) with or without pretreatment of anthocyanin (0, 50, 100 and 200 MUg/ml)
      was measured. After quantifying the percentage of the apoptosis by Annexin V
      assay and APO-BrdU TUNEL assay, we conducted western blot and immunostaining of
      apoptosis-related molecules; Bcl2, BAD, BAX, p53 and caspase-3. To confirm the
      effect of anthocyanin on an ex vivo model, its effect on cultures of the lenses
      of porcine were examined. RESULTS: Anthocyanin reduced cell death of HLE-B3 under
      H2O2-induced oxidative stress in a dose-dependent manner. In Annexin V analysis,
      anthocyanin protected HLE-B3 cells from apoptosis. H2O2 increased the expression
      of BAX, BAD, p53 and caspase-3 in a time-dependent manner, those of which
      anthocyanin significantly decreased. On the other hand, Bcl2 was increased from
      anthocyanin-treated lens cells. And in anthocyanin-treated lens organ culture,
      transparency was maintained. CONCLUSIONS: This study showed that anthocyanin
      protects HLE-B3 cells under oxidative stress from apoptosis, and the mechanism of
      the effect is related to the intrinsic pathway of apoptosis. Anthocyanin has a
      potential in prevention of cataract.

PMID- 24749766
TI  - Thiocarbamate-linked polysulfonate-peptide conjugates as selective hepatocyte
      growth factor receptor binders.
AB  - The capacity of many proteins to interact with natural or synthetic polyanions
      has been exploited for modulating their biological action. However, the
      polydispersity of these macromolecular polyanions as well as their poor
      specificity is a severe limitation to their use as drugs. An emerging trend in
      this field is the synthesis of homogeneous and well-defined polyanion-peptide
      conjugates, which act as bivalent ligands, with the peptide part bringing the
      selectivity of the scaffold. Alternately, this strategy can be used for improving
      the binding of short peptides to polyanion-binding protein targets. This work
      describes the design and first synthesis of homogeneous polysulfonate-peptide
      conjugates using thiocarbamate ligation for binding to the extracellular domain
      of MET tyrosine kinase receptor for hepatocyte growth factor.

PMID- 24749767
TI  - Roles of the ALDH2 and ADH1B genotypes on the association between alcohol intake
      and serum adiponectin levels among Japanese male workers.
AB  - BACKGROUND: Adiponectin secreted from adipose tissue is assumed to mediate
      protective effects on development of metabolic syndrome (MetS) and MetS-related
      diseases such as cardiovascular diseases and cancer. Relationship between alcohol
      intake and circulating adiponectin levels is not consistent among the several
      previous studies. In the present study, we investigated effects of alcohol intake
      and the alcohol-related polymorphisms on serum adiponectin levels among Japanese
      male workers. METHODS: We conducted a cross-sectional design study with 541 male
      workers aged 51.5 +/- 5.9 (mean +/- SD) years in a Japanese plant. Information on
      alcohol intake and other lifestyles was obtained by a self-administered
      questionnaire. Serum total adiponectin (T-Ad), high-molecular-weight adiponectin
      (HMW-Ad), medium-molecular-weight adiponectin (MMW-Ad), and low-molecular-weight
      adiponectin (LMW-Ad) levels were measured by the enzyme-linked immune assay
      system kit. Two genotypes in the alcohol dehydrogenase-1B (ADH1B) and aldehyde
      dehydrogenase-2 (ALDH2) genes were determined using blood sample. In multivariate
      regression analyses, we adjusted for age, body mass index, smoking, and physical
      exercise. RESULTS: Among all subjects, high alcohol consumption of 12 units (1
      unit contains 22.9 g of ethanol) a week or more was negatively associated with T
      Ad levels in the multivariate model, although not significant. When we performed
      analyses separately for each genotype, high alcohol consumption was negatively
      associated with T-Ad, HMW-Ad, and LMW-Ad levels only in those with ADH1B *2/*2.
      Such relationships were not observed in each ALDH2 genotype group. CONCLUSIONS:
      High alcohol consumption was inversely associated with T-Ad, HMW-Ad, and LMW-Ad
      levels in those with ADH1B *2/*2 genotype, but not in those with the other ADH1B
      genotypes. To our knowledge, this is the first study that reports combined
      effects of the alcohol-related polymorphisms and alcohol intake on serum
      adiponectin levels. Additional studies are required to confirm the present
      finding.

PMID- 24749768
TI  - Relationship between respiratory muscle strength and physical performance in
      elderly hospitalized patients.
AB  - Background: Age-related changes in pulmonary function increase respiratory muscle
      work. In the face of this increased demand, poor muscle mass, frequently
      associated with age and multi-morbidity, can reduce endurance and strength of
      respiratory muscles. Furthermore, poor muscle mass may per se contribute to
      exercise intolerance and lower physical performance. The aim of the study was to
      evaluate if respiratory muscle strength has a significant impact on physical
      performance in an elderly population. METHODS: We included 68 patients (28 men
      and 40 women) aged over 65 years (mean 79 years, standard deviation [SD] 6) in
      stable condition at discharge from our acute care geriatric ward. We assessed the
      function of respiratory muscle by measuring maximal inspiratory and expiratory
      pressures (MIP, MEP) and physical function using the 6-Minute Walk Test (6MWT).
      RESULTS: The mean age of our sample was 78.2 years (SD 6.1). There was a
      statistically significant correlation between MIP or MEP and 6MWT distance (MIP,
      r=0.43, p<0.001; MEP, r=0.41, p=0.001). The association between respiratory
      pressures and 6MWT was maintained after adjustment for forced expiratory volume
      in 1 sec (FEV1), forced vital capacity (FVC), age, sex, fat-free mass index
      (FFMI), and leg strength. The multiple regression model showed a significant
      relation between 6-Minute Walk Test distance (6MWD) and both MIP and MEP after
      correction for sex, age, FEV1, and FVC. Furthermore, MEP can significant predict
      poorer performance at 6MWD in a multiple logistic regression model. CONCLUSION:
      Reduced respiratory muscle strength is independently associated with worse
      physical performance in elderly patients.

PMID- 24749769
TI  - An update on emerging drugs for Hodgkin lymphoma.
AB  - INTRODUCTION: Most patients with Hodgkin lymphoma (HL) are cured with modern
      combined modality first-line treatments. Even ~ 50% of patients with
      relapsed/refractory HL can be cured with high-dose chemotherapy (HDCT) and
      autologous stem cell transplantation. However, chemotherapy and radiotherapy
      cause significant acute and long-term side effects and patients relapsing after
      HDCT have a dismal prognosis. New drugs are therefore needed to reduce the
      toxicity of first-line treatments and to increase the efficacy of relapse
      treatments. Moreover, new drugs are needed for the treatment of older patients
      with HL because results with current treatments are disappointing. AREAS COVERED:
      This article discusses promising new drugs for the treatment of classical HL that
      have been evaluated in the last years. There is a focus on the antibody drug
      conjugate brentuximab vedotin and its potential for the future treatment of HL.
      Moreover, data on the histone deacetylase inhibitors panobinostat and
      mocetinostat, the mammalian target of rapamycin inhibitor everolimus, the Janus
      kinase 2 inhibitor SB1518 and the immunomodulatory agent lenalidomide are
      summarized. EXPERT OPINION: Besides improving the prognosis of relapsed patients,
      new drugs should be used to replace the most toxic compounds in first-line
      therapy to reduce acute and long-term toxicities of the treatment.

PMID- 24749770
TI  - Bridging worlds, breaking rules: Clinician perspectives on transitioning young
      people with perinatally acquired HIV into adult care in a low prevalence setting.
AB  - The first generation of young people with perinatally acquired HIV is moving into
      adulthood, precipitating a transition from pediatric to adult care. As the first
      research appraisal of Australian clinician perspectives on this process, this
      article makes a unique contribution by examining the particular challenges
      associated with transitioning this population into adult care in regions of low
      HIV prevalence among young people. Qualitative interviews were conducted with
      twelve pediatric and adult care clinicians and analyzed for dominant and
      diverging themes. Clinicians anticipated significant client vulnerabilities
      during transition and worked beyond the boundaries of their roles and service
      parameters to keep clients engaged as they moved between pediatric and adult
      care. Strategies to strengthen the transition process focused on communication
      and teamwork, informed by and responsive to the needs of individual young people
      and their families. Clinicians working in settings with very small numbers of
      young people with HIV must advocate for a hidden minority with little potential
      for gaining large scale recognition or system changes. New conversations are
      needed to design a stronger and more sustainable transition process for both
      young people living with HIV, and their clinicians who care for them, in low
      prevalence settings.

PMID- 24749772
TI  - Key amino acid associated with acephate detoxification by Cydia pomonella
      carboxylesterase based on molecular dynamics with alanine scanning and site
      directed mutagenesis.
AB  - Insecticide-detoxifying carboxylesterase (CE) gene CpCE-1 was cloned from Cydia
      pomonella. Molecular dynamics (MD) simulation and computational alanine scanning
      (CAS) indicate that Asn 232 in CpCE-1 constitutes an approximate binding hot-spot
      with a binding free energy difference (DeltaDeltaGbind) value of 3.66 kcal/mol.
      The catalytic efficiency (kcat/km) of N232A declined dramatically, and the half
      inhibitory concentrations (IC50) value increased by more than 230-fold.
      Metabolism assay in vitro reveals that the acephate could be metabolized by wild
      CpCE-1, whereas N232A mutation is unable to metabolize the acephate, which
      suggests that the hot-spot Asn 232 is a crucial residue for acephate metabolism.
      Mutation detection suggests that low frequency of Asn 232 replacement occurred in
      Europe field strains. Our MD, CAS, site-directed mutagenesis, and metabolism
      studies introduce a new amino acid residue Asn 232 involved in the metabolism of
      the acephate with CpCE-1, and this method is reliable in insecticide resistance
      mechanism research and prediction of key amino acids in a protein which is
      associated with specific physiological and biochemical functions. 

PMID- 24749771
TI  - Rebamipide attenuates autoimmune arthritis severity in SKG mice via regulation of
      B cell and antibody production.
AB  - Oxidative stress is involved in the pathophysiology of rheumatoid arthritis (RA).
      We investigated the therapeutic potential of rebamipide, a gastroprotective agent
      with a property of reactive oxygen species scavenger, on the development of
      inflammatory polyarthritis and the pathophysiological mechanisms by which
      rebamipide might confer anti-arthritic effects in SKG mice, an animal model of
      RA. Intraperitoneal (i.p.) injection of rebamipide attenuated the severity of
      clinical and histological arthritis. Rebampide treatment reduced the number of T
      helper type 1 (Th1), Th2, Th17, inducible T cell co-stimulator (ICOS)(+)
      follicular helper T (Tfh) transitional type (T2) and mature B cells in the
      spleen, but increased the number of regulatory T (Treg ), CD19(+) CD1d(high)
      CD5(high) , CD19(+) CD25(high) forkhead box protein 3 (FoxP3)(+) regulatory B
      (Breg ) cells, memory B cells, and transitional type 1 (T1) B cells. In addition,
      flow cytometric analysis revealed significantly decreased populations of FAS(+)
      GL-7(+) germinal centre B cells and B220(-) CD138(+) plasma cells in the spleens
      of rebamipide-treated SKG mice compared to controls. Rebamipide decreased
      germinal centre B cells and reciprocally induced Breg cells in a dose-dependent
      manner in vitro. Rebamipide-induced Breg cells had more suppressive capacity in
      relation to T cell proliferation and also inhibited Th17 differentiation from
      murine CD4(+) T cells. Together, these data show that i.p. administration of
      rebamipide suppresses arthritis severity by inducing Breg and Treg cells and
      suppressing Tfh and Th17 cells in a murine model of RA.

PMID- 24749773
TI  - Septic arthritis of the hip in a Cambodian child caused by multidrug-resistant
      Salmonella enterica serovar Typhi with intermediate susceptibility to
      ciprofloxacin treated with ceftriaxone and azithromycin.
AB  - Septic arthritis is a rare complication of typhoid fever. A 12-year-old boy
      without pre-existing disease attended a paediatric hospital in Cambodia with
      fever and left hip pain. A hip synovial fluid aspirate grew multidrug-resistant
      Salmonella enterica ser. Typhi with intermediate susceptibility to ciprofloxacin.
      Arthrotomy, 2 weeks of intravenous ceftriaxone and 4 weeks of oral azithromycin
      led to resolution of symptoms. The optimum management of septic arthritis in drug
      resistant typhoid is undefined. 

PMID- 24749774
TI  - Postnatal changes in cerebral blood flow velocity in term intra-uterine growth
      restricted neonates.
AB  - BACKGROUND: Intra-uterine growth-restricted (IUGR) fetuses are prone to hypoxic
      changes in the brain and neurodevelopmental sequelae in later life. Chronic
      hypoxaemia may also lead to polycythaemia in the fetal and neonatal period. AIM:
      To evaluate venous haematocrit and cerebral blood flow velocity (CBFV) in term
      IUGR neonates in the immediate postnatal period. METHODS: This was a prospective
      observational study of 54 clinically healthy term IUGR neonates as cases and 50
      term, appropriate-for-gestational-age (AGA), healthy neonates as controls. IUGR
      was defined as birthweight <10th per centile for gestational age. Neonates with
      perinatal asphyxia, sepsis and other systemic diseases were excluded. Resistance
      index (RI), pulsatility index (PI), peak systolic velocity (PSV) and vascular
      diameter were measured in the internal carotid, vertebral and middle cerebral
      arteries by transcranial colour Doppler ultrasound between 48 and 72 hours of
      life, along with the estimation of venous haematocrit. Neonates were observed for
      development of any complications until discharge and followed up clinically and
      radiologically for a minimum 6 months. RESULTS: Significantly higher resistance
      (RI and PI) and lower PSV was recorded in all the cerebral arteries of the IUGR
      than the AGA group whereas no difference was observed in vascular diameters. Mean
      haematocrit was significantly higher in the IUGR than in the AGA group [55.7
      (4.22) vs 45.1 (2.79) g/dl]. Haematocrit was positively correlated with RI and
      PI, and negatively correlated with PSV. After discharge, three infants in the
      IUGR group showed hypertonia and delayed developmental milestones along with
      hypoxic changes in MRI of the brain. CONCLUSIONS: Compared with their AGA
      counterparts, higher venous haematocrit and lower CBFV were observed in
      clinically healthy, term IUGR neonates during the early neonatal period. Delayed
      developmental milestones and hypoxic changes were detected by MRI in three
      infants. Since the study was limited by its sample size, larger studies are
      required to document the clinical significance of decreased CBFV and its
      usefulness as a marker of poor prognosis for future neurodevelopment.

PMID- 24749775
TI  - Inferring the past and present connectivity across the range of a North American
      leaf beetle: combining ecological niche modeling and a geographically explicit
      model of coalescence.
AB  - The leaf beetle Chrysomela aeneicollis occurs across Western North America,
      either at high elevation or in small, isolated populations along the coast, and
      thus has a highly fragmented distribution. DNA sequence data (three loci) were
      collected from five regions across the species range. Population connectivity was
      examined using traditional ecological niche modeling, which suggested that gene
      flow could occur among regions now and in the past. We developed geographically
      explicit coalescence models of sequence evolution that incorporated a two
      dimensional representation of the hypothesized ranges suggested by the niche
      modeling estimates. We simulated sequence data according to these models and
      compared them to observed sequences to identify most probable scenarios regarding
      the migration history of C. aeneicollis. Our results disagreed with initial niche
      modeling estimates by clearly rejecting recent connectivity among regions, and
      were instead most consistent with a long period of range fragmentation, extending
      well beyond the last glacial maximum. This application of geographically explicit
      models of coalescence has highlighted some limitations of the use of climatic
      variables for predicting the present and past range of a species and has
      explained aspects of the Pleistocene evolutionary history of a cold-adapted
      organism in Western North America. 

PMID- 24749776
TI  - "If I can grapple with this i can truly be of use in the therapy room": using the
      therapist's own emotional struggles to facilitate effective therapy.
AB  - This study premises that self-of-the-therapist work is pivotal in the development
      of effective therapists. However, therapy models vary in their goals for this
      work and the means of accomplishing them. This study presents the perspective of
      the person-of-the-therapist Training (POTT) model that prioritizes the ability to
      consciously and purposefully use the self-as-is at the moment of contact with the
      client over the traditional goal of therapists working to resolve their issues. A
      key underlying assumption of the model proposes that therapists' core issues
      (referred to as "signature themes") are potent resources that can be tapped into
      to connect, assess and intervene effectively with clients. The study presents the
      model and illustrates the use of signature themes in clinical work. 

PMID- 24749777
TI  - Management of morphoea: results of a national survey of U.K. clinicians.

PMID- 24749778
TI  - Insights into the uptake processes of wastewater-borne pharmaceuticals by
      vegetables.
AB  - An increasing number of reports on plant uptake of pharmaceutical compounds (PCs)
      have been recently published, raising concerns of human exposure through dietary
      intake. In this study, PC uptake and translocation were evaluated in cucumber and
      tomato plants to elucidate the effects of PC physicochemical properties, soil
      type, and irrigation-water quality. Nonionic PCs were taken up and accumulated at
      higher levels in plants grown in soils of lower organic matter and clay content.
      While the concentration of most PCs in cucumber and tomato leaves were of similar
      order, their concentrations in the tomato fruit were much lower than in the
      cucumber fruit. This is related to differences in fruit physiology. Our data
      suggest that irrigation with treated wastewater reduces the bioavailability of
      acidic PCs for uptake by cucumber plants as compared to fresh water irrigation.
      This study sheds light on factors affecting the uptake of PCs by crops irrigated
      with treated wastewater, the governing role of PCs' physicochemical properties
      along with the physiological nature of the plant, soil properties and water
      quality that together determine uptake, translocation, and accumulation within
      plant organs. Occurrence of metabolites in plant suggests that PC metabolism has
      to be evaluated to reveal the total uptake. 

PMID- 24749779
TI  - Behavioral economic measures of alcohol reward value as problem severity
      indicators in college students.
AB  - The aims of the current study were to examine the associations among behavioral
      economic measures of alcohol value derived from 3 distinct measurement
      approaches, and to evaluate their respective relations with traditional
      indicators of alcohol problem severity in college drinkers. Five behavioral
      economic metrics were derived from hypothetical demand curves that quantify
      reward value by plotting consumption and expenditures as a function of price,
      another metric measured proportional behavioral allocation and enjoyment related
      to alcohol versus other activities, and a final metric measured relative
      discretionary expenditures on alcohol (RDEA). The sample included 207 heavy
      drinking college students (53% female) who were recruited through an on-campus
      health center or university courses. Factor analysis revealed that the alcohol
      valuation construct comprises 2 factors: 1 factor that reflects participants'
      levels of alcohol price sensitivity (demand persistence), and a second factor
      that reflects participants' maximum consumption and monetary and behavioral
      allocation toward alcohol (amplitude of demand). The demand persistence and
      behavioral allocation metrics demonstrated the strongest and most consistent
      multivariate relations with alcohol-related problems, even when controlling for
      other well-established predictors. The results suggest that behavioral economic
      indices of reward value show meaningful relations with alcohol problem severity
      in young adults. Despite the presence of some gender differences, these measures
      appear to be useful problem indicators for men and women.

PMID- 24749780
TI  - R-CHOP with iodine-131 tositumomab consolidation for advanced stage diffuse large
      B-cell lymphoma (DLBCL): SWOG S0433.
AB  - Radiolabelled antiCD-20 antibodies have demonstrated single agent activity in
      relapsed diffuse large B-cell lymphoma (DLBCL). The S0433 clinical trial enrolled
      patients with newly diagnosed, advanced stage or bulky stage II, histologically
      confirmed DLBCL. Patients received six cycles of R-CHOP (rituximab,
      cyclophosphamide, doxorubicin, vincristine, prednisone), two cycles of CHOP, then
      iodine-131 tositumomab radioimmunotherapy consolidation 30-60 d after completion
      of chemotherapy. The primary endpoint was 2-year progression-free survival (PFS).
      Eighty-four eligible patients were enrolled, and 56 patients completed the entire
      course of protocol treatment. Of the 84 patients evaluable for treatment
      response, 72 [86%, 95% confidence interval (CI): 76-92%] achieved a partial
      response (n = 21) or a confirmed (n = 41) or unconfirmed (n = 10) complete
      response to therapy. With a median follow-up of 3.9 years, the 2-year PFS
      estimate is 69% and the 2-year overall survival estimate is 77%. Rituximab levels
      at time of radioimmunotherapy did not correlate with toxicity or outcome. Twenty
      percent of patients had double hit features (MYC+; BCL2+) by
      immunohistochemistry, and had inferior outcome. These current results suggest
      that the incorporation of novel agents earlier in therapy may ultimately have
      greater impact in DLBCL, as early progressions, deaths and declining performance
      status during CHOP chemotherapy limited the number of patients who ultimately
      could benefit from radioimmunotherapy consolidation.

PMID- 24749781
TI  - Ferroelastic domain organization and precursor control of size in solution-grown
      hafnium dioxide nanorods.
AB  - We demonstrate that the degree of branching of the alkyl (R) chain in a Hf(OR)4
      precursor allows for control over the length of HfO2 nanocrystals grown by
      homocondensation of the metal alkoxide with a metal halide. An extended
      nonhydrolytic sol-gel synthesis has been developed that enables the growth of
      high aspect ratio monoclinic HfO2 nanorods that grow along the [100] direction.
      The solution-grown elongated HfO2 nanorods show remarkable organization of twin
      domains separated by (100) coherent twin boundaries along the length of the
      nanowires in a morphology reminiscent of shape memory alloys. The sequence of
      finely structured twin domains each spanning only a few lattice planes originates
      from the Martensitic transformation of the nanorods from a tetragonal to a
      monoclinic structure upon cooling. Such ferroelastic domain organization is
      uncharacteristic of metal oxides and has not thus far been observed in bulk HfO2.
      The morphologies observed here suggest that, upon scaling to nanometer-sized
      dimensions, HfO2 might exhibit mechanical properties entirely distinctive from
      the bulk. 

PMID- 24749783
TI  - Is burnout solely job-related? A critical comment.
AB  - Within the field-dominating, multidimensional theory of burnout, burnout is
      viewed as a work-specific condition. As a consequence, the burnout syndrome
      cannot be investigated outside of the occupational domain. In the present paper,
      this restrictive view of burnout's scope is criticized and a rationale to decide
      between a work-specific and a generic approach to burnout is presented. First,
      the idea that a multidimensional conception of burnout implies a work-restricted
      scope is deconstructed. Second, it is shown that the burnout phenomenon cannot be
      confined to work because chronic, unresolvable stress - the putative cause of
      burnout - is not limited to work. In support of an integrative view of health, it
      is concluded that the field-dominating, multidimensional theory of burnout should
      abandon as groundless the idea that burnout is a specifically job-related
      phenomenon and define burnout as a multi-domain syndrome. The shift from a work
      specific to a generic approach would allow both finer analysis and wider
      synthesis in research on chronic stress and burnout. 

PMID- 24749784
TI  - Effect of health protective factors on health deficit accumulation and mortality
      risk in older adults in the Beijing Longitudinal Study of Aging.
AB  - OBJECTIVES: To evaluate transitions in health status and risk of death in older
      adults in relation to baseline health deficits and protective factors. DESIGN:
      Prospective cohort study with reassessments at 5, 8, and 15 years. SETTING:
      Secondary analysis of data from the Beijing Longitudinal Study on Aging.
      PARTICIPANTS: Urban and rural community-dwelling people aged 55 and older at
      baseline (n = 3,275), followed from 1992 to 2007, during which time 51% died.
      MEASUREMENTS: Health status was quantified using the deficit accumulation-based
      frailty index (FI), constructed from 30 intrinsic health measures. A protection
      index was constructed using 14 extrinsic items (e.g., exercise, education). The
      probabilities of health changes, including death, were evaluated using a
      multistate transition model. RESULTS: Women had more health deficits (mean
      baseline FI 0.13 +/- 0.11) than did men (mean baseline FI 0.11 +/- 0.10).
      Although health declined on average (mean FIs increased), improvement and
      stability were common. Baseline health significantly affected health transitions
      and survival over various follow-up durations (odds ratio (OR) = 1.27, 95%
      confidence interval (CI) = 1.17-1.37 for men; OR = 1.24, 95% CI = 1.16-1.33 for
      women for each increment of deficits). Each protective factor reduced the risk of
      health decline and the risk of death in men and women by 13% to 25%. CONCLUSION:
      Deficit accumulation-based transition modeling demonstrates persisting effects of
      baseline health status on age-related health outcomes. Some mitigation by
      protective factors can be demonstrated, suggesting that improving physical and
      social conditions might be beneficial.

PMID- 24749782
TI  - Amphetamine-induced release of dopamine in primate prefrontal cortex and
      striatum: striking differences in magnitude and timecourse.
AB  - The psychostimulant amphetamine (AMPH) is frequently used to increase
      catecholamine levels in attention disorders and positron emission tomography
      imaging studies. Despite the fact that most radiotracers for positron emission
      tomography studies are characterized in non-human primates (NHPs), data on
      regional differences of the effect of AMPH in NHPs are very limited. This study
      examined the impact of AMPH on extracellular dopamine (DA) levels in the medial
      prefrontal cortex and the caudate of NHPs using microdialysis. In addition to
      differences in magnitude, we observed striking differences in the temporal
      profile of extracellular DA levels between these regions that can likely be
      attributed to differences in the regulation of dopamine uptake and biosynthesis.
      The present data suggest that cortical DA levels may remain elevated longer than
      in the caudate which may contribute to the clinical profile of the actions of
      AMPH. Using microdialysis probes implanted in the cortex and caudate region of
      non-human primate brains, we observed in vivo differences in the magnitude and
      temporal profile of extracellular dopamine levels in response to intravenous
      amphetamine administration. 

PMID- 24749785
TI  - A multivalent chimeric vaccine composed of Schistosoma mansoni SmTSP-2 and Sm29
      was able to induce protection against infection in mice.
AB  - Schistosoma mansoni is a blood fluke parasite responsible for schistosomiasis.
      The best long-term strategy to control schistosomiasis is through immunization
      combined with drug treatment. In this study, we cloned, expressed and purified
      SmTSP-2 fused to the N- and C-terminal halves of Sm29 and tested these chimeras
      as vaccine candidates using an adjuvant approved to be used in humans. The
      results demonstrated that vaccination with SmTSP-2 fused to N- or C-terminus of
      Sm29-induced reduction in worm burden and liver pathology when compared to
      control animals. Additionally, we detected high levels of mouse-specific IgG,
      IgG1 and IgG2a against both chimeras and significant amounts of IFN-gamma and TNF
      alpha and no IL-4. Finally, studies with sera from patients resistant to
      infection and living in schistosomiasis endemic areas revealed high levels of
      specific IgG to both chimeras when compared to healthy individuals. In
      conclusion, SmTSP-2/Sm29 chimeras tested here induced partial protection against
      infection and might be a potential vaccine candidate. 

PMID- 24749787
TI  - Synergy between graphene and Au nanoparticles (heterojunction) towards quenching,
      improving Raman signal, and UV light sensing.
AB  - Here, we developed a simple method for obtaining a heterojunction composed of
      graphene (G) and surfactant-coated Au nanoparticles (NPs) to measure film
      conductivity and surface enhanced Raman scattering (SERS). Monolayer G is
      obtained by chemical vapor deposition (CVD) and transferred via poly(methyl
      methacrylate) (PMMA) to microfabricated Au electrodes, glass, and silicon. Post
      synthesis treatments of G with PMMA and ozone (O3) showed 1 and 6 orders of
      magnitude decrease in film conductivity, respectively. The heterojunction
      formation with Au NPs had no major effect on G conductivity. In this work is
      demonstrated that G quenches more than 90% of the combined photoluminescence and
      fluorescence of Au NPs and Rhodamine B (RhB), respectively. Signal quenching
      permitted quantitative analysis of SERS of RhB on various substrates including as
      transferred graphene, oxidized graphene (OG), and the heterojunction. While G is
      mainly responsible for quenching photoluminescence and fluorescence, ~3 orders of
      magnitude increase SERS activity for RhB was accomplished by the heterojunction.
      Finally, we wanted to correlate changes in film current during UV light sensing
      experiments. We found striking differences in the sensing profiles at different
      UV energies. 

PMID- 24749786
TI  - Vessel-associated myogenic precursors control macrophage activation and clearance
      of apoptotic cells.
AB  - Swift and regulated clearance of apoptotic cells prevents the accumulation of
      cell remnants in injured tissues and contributes to the shift of macrophages
      towards alternatively activated reparatory cells that sustain wound healing.
      Environmental signals, most of which are unknown, in turn control the efficiency
      of the clearance of apoptotic cells and as such determine whether tissues
      eventually heal. In this study we show that vessel-associated stem cells
      (mesoangioblasts) specifically modulate the expression of genes involved in the
      clearance of apoptotic cells and in macrophage alternative activation, including
      those of scavenger receptors and of molecules that bridge dying cells and
      phagocytes. Mesoangioblasts, but not immortalized myoblasts or neural precursor
      cells, enhance CD163 membrane expression in vitro as assessed by flow cytometry,
      indicating that the effect is specific. Mesoangioblasts transplanted in acutely
      or chronically injured skeletal muscles determine the expansion of the population
      of CD163(+) infiltrating macrophages and increase the extent of CD163 expression.
      Conversely, macrophages challenged with mesoangioblasts engulf significantly
      better apoptotic cells in vitro. Collectively, the data reveal a feed-forward
      loop between macrophages and vessel-associated stem cells, which has implications
      for the skeletal muscle homeostatic response to sterile injury and for diseases
      in which homeostasis is jeopardized, including muscle dystrophies and
      inflammatory myopathies. 

PMID- 24749788
TI  - Morphological analysis of quiescent and activated keratocytes: a review of ex
      vivo and in vivo findings.
AB  - Keratocytes are specialized, neural crest-derived mesenchymal cells occupying
      approximately 3% of the corneal stromal volume. They reside between the collagen
      lamellae and are responsible for the secretion of extracellular matrix
      macromolecules, thus contributing to the corneal transparency and integrity.
      During the regeneration process after infection, traumata and refractive surgery,
      the keratocytes undergo transition into divergent phenotypes, which are referred
      to as "activated keratocytes". Quite shortly after injury, the keratocytes lose
      their quiescence, enter into the cell cycle and migrate toward the site of
      injury. In certain types of injury, which affect the integrity of basement
      membrane, activated keratocytes also participate in wound closure by production
      of alpha-smooth muscle actin (alpha-SMA). Since the activated keratocytes are the
      major cell type contributing to tissue repair during corneal wound healing, their
      morphological and biochemical properties have been studied in details in
      experimental studies using light and electron microscopy. More recently, emerging
      of in vivo microscopy techniques has opened new possibilities to investigate
      cornea in vivo. The non-invasive nature of this imaging modality enables repeated
      examination of the same tissue over time and is an ideal tool to rapidly and
      accurately investigate corneal wound healing. However, the in vivo data on
      activated keratocytes are not as uniform as data from experimental ex vivo
      studies. There is still inconsistency in the literature findings on activated
      phenotypes, and often the described morphologies cannot be appreciated in in vivo
      images. In this article, a literature review was performed in order to interpret
      the morphology of different activated phenotypes, based on biological processes
      underlying the morphological alterations.

PMID- 24749789
TI  - Physical and antibacterial properties of acai edible films formulated with thyme
      essential oil and apple skin polyphenols.
AB  - Thyme essential oil (TEO) and apple skin polyphenols (ASP) are natural compounds
      considered as generally recognized as safe by FDA, with biological effects
      against bacteria and fungi. This work aimed to evaluate physical and
      antimicrobial properties of acai edible films formulated with TEO and ASP at 3%
      and 6% (w/w) individually or combined at 3% (w/w) each. Physical properties
      studied include mechanical resistance, water vapor permeability (WVP), color, and
      thermal resistance. Antimicrobial activity against Listeria monocytogenes was
      determined using the overlay diffusion test. Addition of ASP resulted in improved
      mechanical properties. TEO at 6% (w/w) resulted in increased elongation. ASP
      films had significant higher WVP than control film. ASP films were lighter and
      had more red color than other films. Incorporation of ASP resulted in improved
      film thermal stability, whereas TEO caused rapid thermal decomposition. Presence
      of clusters was observed on the surface of films. Addition of ASP resulted in a
      smoother surface, whereas addition of TEO led to the formation of crater-like
      pits on the film surface. Acai edible film incorporated with 6% (w/w) TEO
      presented the highest antimicrobial activity. However, both antimicrobials are
      necessary in the acai films in order to obtain edible films with suitable
      physical-mechanical properties. The results of the present study showed that TEO
      and ASP can be used to prepare acai edible films with adequate physical
      mechanical properties and antimicrobial activity for food applications by direct
      contact. PRACTICAL APPLICATION: Developed acai edible films presented
      antimicrobial activity against L. monocytogenes and good physical-mechanical
      properties, showing the potential use of acai edible films in food preservation.

PMID- 24749790
TI  - Cognitive deficit awareness in schizophrenia: absent, intact, or somewhere in
      between?
AB  - INTRODUCTION: Cognitive impairment is a pervasive feature of schizophrenia, and
      is a major determinant of the functional disability that is characteristic of the
      disorder. However, research investigating whether patients with schizophrenia
      show a deficit awareness remains unclear. The present study aimed to replicate
      and extend previous research comparing subjective and objective measures of
      cognition. METHODS: . Thirty patients with a diagnosis of schizophrenia or
      schizoaffective disorder were administered the subjectively assessed
      Schizophrenia Cognitive Rating Scale (SCoRS) and the objective Brief Assessment
      of Cognition in Schizophrenia (BACS), which each assess overall global
      functioning and four specific neurocognitive domains (i.e., Verbal Memory,
      Working Memory, Processing Speed, and Reasoning and Problem Solving). Because
      deficit awareness may influence the likelihood of patients engaging in treatments
      designed to improve cognitive functioning, patients' attitudes towards such
      therapies were also contrasted with these subjective and objective measures of
      cognitive functioning. RESULTS: Patients' subjective appraisals did not
      significantly correlate with the objective neuropsychological assessments for
      global functioning or any specific neurocognitive domains. However, patients
      accurately deduced that their memory domains were more impaired than the other
      domains, and there was a trend for patients to exaggerate their Reasoning and
      Problem Solving deficits. This suggests that patients show some level of deficit
      awareness, when overestimating "deficits" for domains that are not impaired.
      Finally subjective, but not objective, measures of cognitive functioning
      correlated significantly with willingness to participate in cognitive-enhancing
      therapies. CONCLUSIONS: These results suggest that although patients' perceptions
      of their cognitive function are no substitute for objective neuropsychological
      test data, patients do possess a level of deficit awareness which may, in turn,
      influence willingness to participate in interventions such as cognitive
      rehabilitation.

PMID- 24749791
TI  - Speed of adaptation and genomic footprints of host-parasite coevolution under
      arms race and trench warfare dynamics.
AB  - Coevolution between hosts and their parasites is expected to follow a range of
      possible dynamics, the two extreme cases being called trench warfare (or Red
      Queen) and arms races. Long-term stable polymorphism at the host and parasite
      coevolving loci is characteristic of trench warfare, and is expected to promote
      molecular signatures of balancing selection, while the recurrent allele fixation
      in arms races should generate selective sweeps. We compare these two scenarios
      using a finite size haploid gene-for-gene model that includes both mutation and
      genetic drift. We first show that trench warfare do not necessarily display
      larger numbers of coevolutionary cycles per unit of time than arms races. We
      subsequently perform coalescent simulations under these dynamics to generate
      sequences at both host and parasite loci. Genomic footprints of recurrent
      selective sweeps are often found, whereas trench warfare yield signatures of
      balancing selection only in parasite sequences, and only in a limited parameter
      space. Our results suggest that deterministic models of coevolution with infinite
      population sizes do not predict reliably the observed genomic signatures, and it
      may be best to study parasite rather than host populations to find genomic
      signatures of coevolution, such as selective sweeps or balancing selection. 

PMID- 24749792
TI  - Comparison of mortality following hospitalisation for ulcerative colitis in
      Scotland between 1998-2000 and 2007-2009.
AB  - BACKGROUND: Scottish nationwide linkage data from 1998 to 2000 demonstrated high
      3-year mortality in patients hospitalised with ulcerative colitis (UC). AIM: To
      compare 3-year mortality, and factors related to mortality, in Scottish patients
      hospitalised with UC between 1998-2000 and 2007-2009. METHODS: The Scottish
      Morbidity Records and linked datasets were used to assess 3-year mortality,
      standardised mortality ratio (SMR) and multivariate analyses of factors
      associated with 3-year mortality. The 3-year mortality was determined after four
      admission types: surgery-elective or emergency; medical-elective or emergency.
      Age-standardised mortality rates (ASR) were used to compare mortality rates
      between periods. RESULTS: Ulcerative colitis admissions increased from 10.6 in
      Period 1 to 11.6 per 100 000 population per year in Period 2 (P = 0.046). Crude
      and adjusted 3-year mortality fell between time periods (crude 12.2% to 8.3%;
      adjusted OR 0.59, CI 0.42-0.81, P = 0.04). Adjusted 3-year mortality following
      emergency medical admission (OR 0.58, CI 0.39-0.87, P = 0.003) and in patients
      >65 years (38.8% to 28.7%, P = 0.02) was lower in Period 2. The SMR in period 1
      was 3.04 and 2.96 in Period 2. Directly age-standardised mortality decreased from
      373 (CI 309-437) to 264 (CI 212-316) per 10 000 person-years. On multivariate
      analysis, increasing age (50-64 years OR 7.11 (CI 2.77-18.27, P < 0.05); 65-74
      years OR 14.70 (CI 5.65-38.25 P < 0.05); >75 years OR 46.42 (CI 18.29-117.78, P <
      0.001) and co-morbidity (OR 3.02, CI 1.72-5.28, P < 0.001) were significantly
      associated with 3-year mortality in Period 2. CONCLUSIONS: Comparisons of crude
      and adjusted mortality rates suggest significant improvement in outcome over the
      last decade - however, mortality remains high, and older age and co-morbidity are
      important predictors of outcome.

PMID- 24749793
TI  - Maternal sleep duration and complaints of vital exhaustion during pregnancy is
      associated with placental abruption.
AB  - OBJECTIVE: Sleep disorders are associated with cardiovascular complications and
      preterm delivery (PTD). Insufficient sleep results in metabolic alterations and
      increased inflammation, both known to contribute to placental abruption
      (abruption), a determinant of PTD. We examined associations of abruption with
      sleep duration and complaints of vital exhaustion. METHODS: The study included
      164 abruption cases and 160 controls in a multicenter study in Peru. Data on
      habitual sleep duration and vital exhaustion during the first 6 months of
      pregnancy were elicited during interviews conducted following delivery. Women
      were categorized according to short, normal and long sleep duration (<=6, 7-8 and
      >=9 h); and frequency of feeling exhausted. Odds ratios (OR) and 95% confidence
      intervals (CI) were calculated. RESULTS: Short and long sleep durations were
      associated with increased odds of abruption. The ORs of abruption in relation to
      short (<=6 h) and long (>=9 h) sleep duration were 2.0 (95% CI 1.1-3.7) and 2.1
      (95% CI 1.1-4.1), compared with normal sleep duration (7-8 h). Complaints of
      vital exhaustion were also associated with abruption (OR = 2.37; 95% CI 1.46
      3.85), and were independent of sleep duration. CONCLUSION: We extend the existing
      literature and support the thesis that maternal sleep habits and disorders should
      be assessed among pregnant women.

PMID- 24749794
TI  - The passage of meconium alone is not a sign of correctly positioned anus.
AB  - OBJECTIVE: The aim of this study is to determine the consequences of delayed
      presentation of anorectal malformations and emphasize the causes of delayed
      diagnosis of these malformations. METHODS: We retrospectively reviewed 54
      neonatal patients with a diagnosis of anorectal malformations. Group 1 consisted
      of 35 patients diagnosed within the first 48 h of life and Group 2 included 19
      patients diagnosed after 48 h of life. RESULTS: Obstructive symptoms at the time
      of diagnosis, overall complications and the mean postoperative hospitalization
      period in Group 2 were markedly higher than that of Group 1. A comprehensive
      neonatal examination within the first 48 h of life was performed in 32 (91.4%)
      patients in Group 1 and 5 (26.3%) of the patients in Group 2 (p < 0.001).
      CONCLUSIONS: The passage of meconium is not the only sign of correctly positioned
      anus. A careful physical examination and awareness of this anomaly are of great
      importance in making a timely diagnosis of anorectal malformations.

PMID- 24749795
TI  - Maternal plasma levels of interleukin-6, C-reactive protein, vitamins C, E and A,
      8-isoprostane and oxidative status in women with preterm premature rupture of
      membranes.
AB  - OBJECTIVE: Preterm premature rupture of membranes (PPROM) is associated with
      significant maternal and perinatal morbidity. This study examined maternal
      oxidative stress in PPROM. METHODS: This was a prospective cross-sectional study
      conducted in a university hospital. A total of 72 pregnant women were recruited
      into two groups, those with PPROM (38 cases) and those without PPROM (34
      controls) matched for gestational age. Plasma interleukin-6, C-reactive protein,
      vitamins C, E and A, 8-isoprostane, total oxidant status (TOS) and antioxidant
      status (TAS) were determined for all study participants and the data were
      compared between the PPROM and control groups. RESULTS: Both case and control
      groups were comparably matched in age, parity, gestational age and smoking
      status. There was a significant association between low 8-isoprostane, low
      vitamin C and high total oxidant status and the occurrence of PPROM (p < 0.001).
      CONCLUSIONS: Plasma vitamin C and 8-isoprostane levels were lower and TOS higher
      in women with PPROM. Further research is needed to identify robust biological
      markers for the prevention and also prognosis of PPROM.

PMID- 24749796
TI  - Diagnostic value of elevated CXCR4 and CXCL12 in neonatal sepsis.
AB  - OBJECTIVE: Neonatal sepsis remains a major cause of morbidity and mortality in
      newborns. The chemokine CXCL12 and its receptor CXCR4 are now known to play an
      important role in inflammatory states. However, it is unclear how chemokines
      respond to late-onset neonatal sepsis. METHODS: Patients were classified into the
      groups of septic and non-septic ones. Samples of venous blood were obtained from
      all septic and non-septic newborns at the beginning and within 48-72 h after
      initiation of treatment. Serum levels of CXCR4 and CXCL12 were measured. RESULTS:
      Concentrations of IL-6, CXCR4 and CXCL12 at the time of diagnosis were
      significantly higher in the septic neonates compared with the non-septic ones.
      Additionally, there were statistically significant differences in septic neonates
      between the first and the second levels of IL-6, CXCR4, CXCL12 and I/T ratio. ROC
      curve analyses revealed that IL-6, CXCR4, CXCL12 and I/T ratio resulted in
      significant AUC with respect to early identification of septic neonates.
      Univariate logistic regression analysis showed that increased IL-6, CXCR4 and
      CXCL12 were strong predictors of neonatal LOS. CONCLUSIONS: Serum CXCR4 and
      CXCL12 levels increase in septic neonates and that both chemokines decrease
      within 48-72 h of treatment. Serum concentrations of both chemokines represent
      promising novel biomarkers for neonatal sepsis.

PMID- 24749797
TI  - Anal incontinence in women with recurrent obstetric anal sphincter rupture: a
      case control study.
AB  - OBJECTIVES: To determine the risk of recurrent anal sphincter rupture (ASR), and
      compare the risk of anal incontinence (AI) after recurrent ASR, with that seen in
      women with previous ASR who deliver by caesarean section or vaginally without
      sustaining a recurrent ASR. METHODS: Women with recurrent ASR between January
      2000 and June 2011 were identified at two delivery wards in Copenhagen. The women
      answered a questionnaire with a validated scoring system for AI (St. Mark's
      score), and the results were compared with those obtained in two control groups:
      women with subsequent uncomplicated vaginal delivery or caesarean section.
      RESULTS: There were 93 437 vaginal deliveries. ASR occurred in 5.5% (n = 2851) of
      the nulliparous and 1.5% (n = 608) of the multiparous women. Recurrent ASR
      occurred in 8% (n = 49) of whom 50% reported symptoms of AI. We found no
      difference in the occurrence of AI between women with recurrent ASR, and those
      who delivered vaginally without repeat ASR (p = 0.37; OR = 2.0) or by caesarean
      section (p = 0.77; OR = 1.3). CONCLUSION: Women with a past history of ASR have
      an 8% risk of recurrence. AI affects half of the women with recurrent ASR. Larger
      studies are required to confirm our findings.

PMID- 24749798
TI  - Pregnancy outcome after induction of labor in women with previous cesarean
      section.
AB  - OBJECTIVE: As conflicting data exist concerning the safety of induction of labor
      (IoL) in women with previous single lower segment cesarean section (CS), we aimed
      to assess pregnancy outcome following IoL in such patient population. METHODS:
      All singleton pregnancies with previous single CS which underwent IoL during 2008
      2012 were included (study group). Their pregnancy outcome was compared to those
      pregnancies with previous single CS that admitted with spontaneous onset of labor
      (control group). RESULTS: Overall, 1898 pregnancies were eligible, of them, 259
      underwent IoL, and 1639 were admitted with spontaneous onset of labor. Parity,
      gestational age at delivery and birthweight were similar. Women in the study
      group were more likely to undergo CS mainly due to labor dystocia (8.1 versus
      3.7%, p < 0.01). The rate of CS due to non-reassuring fetal heart rate was
      similar. No difference was found in the rate of uterine rupture/dehiscence. Short
      term neonatal outcome was similar between the groups. On multivariable logistic
      regression analysis, IoL was not independently associated with uterine rupture
      (OR 1.33, 95% C.I 0.46-3.84, p = 0.59). CONCLUSION: Our data suggest that IoL in
      women with one previous low segment CS neither increases the risk of uterine
      rupture nor adversely affects immediate neonatal outcome.

PMID- 24749799
TI  - Relationship between reduced folate carrier gene polymorphism and non-syndromic
      cleft lip and palate in Indian population.
AB  - OBJECTIVE: Folate metabolism involves absorption, transport, modifications and
      interconversions of folates. The reduced folate carrier does not participate
      directly in folate metabolism but plays a major role in intracellular transport
      of metabolically active 5-methyltetrahydrofolate and maintains the intracellular
      concentrations of folate. The purpose of this study was to identify the
      prevalence of reduced folate carrier 1 (RFC1) A80G polymorphism and to further
      delineate its association with non-syndromic cleft lip and palate (NSCLP) in a
      south Indian population. METHODS: In the present case-control study, we studied
      RFC1 gene A80G polymorphism to evaluate its impact on NSCLP risk in south Indian
      population. Blood samples of 142 cases with NSCLP and 141 controls were collected
      and genotyped using PCR-RFLP. RESULTS: The genotype distribution in the control
      group followed Hardy-Weinberg equilibrium (p = 0.633). The G allele frequency of
      cases was 64.8% (184/284) and was significantly lower than that found in the
      control group 56.4% (160/282). The genotype distributions between NSCLP cases and
      controls was not significantly different (p = 0.131). The allelic model
      significantly increased the risk of NSCLP (G versus A; OR = 1.40; 95% CI: 1.00
      1.97; p = 0.050). In subgroup analysis, the A80G variant showed significant
      association for the CLP group in dominant and allelic models. CONCLUSIONS:
      Altogether, our findings support the hypothesis that RFC1 A80G variant may
      contribute to NSCLP susceptibility in a south Indian population.

PMID- 24749800
TI  - Obstetric dilemma on the most appropriate management of Creutzfeldt-Jakob disease
      in pregnancy: seventh case presentation, literature review and new insight.
AB  - Prion diseases (PDs) are fatal neurological disorders that are thought to be
      caused by the accumulation of an altered variant of a benign, widely expressed
      protein (PrPC) into a distinct pathological conformation(s) (PrPSc). The PDs are
      so rare but lethal pathologies that need an early diagnosis to adequately support
      the infected patient. A maternal-fetal transmission during pregnancy has been
      supposed to be on the basis of animal studies, but till now the effective
      vertical transmission in humans has not been proved. We present a case of
      infected pregnant woman with a peculiar pregnancy course and outcome. We also
      provided a systematic literature review to find the best obstetrical management
      of women affected by prionic disease during pregnancy. The available data
      underline the potential risk of prenatal and postnatal transmission of the
      disease but do not permit to define the exact molecular mechanism of
      transmission, the best follow-up and recommendations that are useful in both
      obstetrical and neonatal practice. At present awaiting for further clarifications
      about this topic, it is mandatory to personalize the management of this rare
      pregnancy complication according to the maternal-fetal well-being status.

PMID- 24749801
TI  - Low molecular weight heparin treatment and impact of inherited thrombophilia type
      in pregnancies with previous adverse outcome.
AB  - OBJECTIVE: To assess the impact of low molecular weight heparin (LMWH) treatment
      in 50 pregnancies of women with inherited thrombophilia and adverse pregnancy
      outcome (APO) in previous untreated pregnancies. The impact of "Conventional"
      (FVL, PT, AT, PC, PS) and "Novel" (MTHFR, PAI-1, ACE) thrombophilias on APO was
      investigated. METHODS: The primary outcomes (PO) were: early and late pregnancy
      loss (EPL, LPL), preterm birth (PTB) or term birth (TB) compared to the last
      untreated pregnancies of the same women. Secondary outcomes (SO) were APO in LMWH
      treated and last untreated pregnancies ended with birth. PO and SO were compared
      in relation to the thrombophilia type. RESULTS: LMWH decreased EPL and LPL rate
      and improved TB rate compared with last untreated pregnancies (p < 0.001). There
      were less PTB (p = 0.019) and no cases of intrauterine fetal death (IUFD) (p =
      0.0019) in LWMH-treated pregnancies. The division to Conventional and Novel
      thrombophilias showed: (a) difference between pregnancy losses and birth rate (p
      = 0.0069) and (b) no difference in the prevalence of APO in untreated pregnancies
      ended with birth. CONCLUSIONS: LMWH treatment improves pregnancy outcome in women
      with inherited thrombophilia and APO in previous pregnancies. Novel
      thrombophilias have the equal impact on the pregnancy outcome compared to the
      Conventional thrombophilias.

PMID- 24749802
TI  - Racial/ethnic variations in perineal length and association with perineal
      lacerations: a prospective cohort study.
AB  - OBJECTIVE: To examine the association between race/ethnicity, perineal length and
      the risk of perineal laceration. METHODS: This is a prospective cohort study of a
      diverse group of women with singleton gestations in the third trimester of
      pregnancy. Perineal length was measured and mean values calculated for several
      racial/ethnic groups. Chi-squared analyses were used to examine rates of severe
      perineal laceration (third or fourth degree laceration) by race/ethnicity among
      women considered to have a short perineal length. Further, subgroup analyses were
      performed comparing nulliparas to multiparas. RESULTS: Among 344 study
      participants, there was no statistically significant difference in mean perineal
      length by race/ethnicity (White 4.0 +/- 1.1 cm, African-American 3.7 +/- 1.0 cm,
      Latina 4.1 +/- 1.1 cm, Asian 3.8 +/- 1.0 cm, and other/unknown 4.0 +/- 0.9 cm).
      Considering parity, more multiparous Asian and African-American women had a short
      perineal length (20.7 and 23.5%, respectively, p = 0.05). Finally, the rate of
      severe perineal lacerations in our cohort was 2.6% overall, but was 8.2% among
      Asian women (p = 0.04). CONCLUSIONS: We did not find a relationship between short
      perineal length and risk of severe perineal laceration with vaginal delivery, or
      a difference in mean perineal length by maternal race/ethnicity. However, we did
      find that women of different racial/ethnic groups have varying rates of severe
      perineal laceration, with Asian women comprising the highest proportion.

PMID- 24749803
TI  - Modified myocardial performance index is not affected in fetuses with an isolated
      echogenic focus in the left ventricle.
AB  - OBJECTIVES: We prospectively investigated the efficacy of modified myocardial
      performance index (mod-MPI) in the assessment of cardiac functions in fetuses
      with and without an isolated hyperechogenic focus (IHF) in the left ventricle and
      compared with conventional fetal echocardiography. METHODS: The study group
      consisted of 50 fetuses with only an IHF in the left ventricle, without any other
      cardiac or extracardiac anomalies; 50 fetuses without IHF served as controls. All
      fetal echocardiographic studies were performed between 20th and 24th weeks of
      gestation. Left ventricular functions were evaluated with both conventional
      echocardiographic methods (peak velocity of the aortic valve, mitral E/A ratio,
      fractional shortening) and mod-MPI. RESULTS: There was no statistically
      significant difference between the groups in terms of maternal age, BMI or
      gestational age at the time of examination (p > 0.05 for all). No statistically
      significant differences were found between the findings of conventional
      echocardiographic measurements and left ventricular mod-MPI between the study and
      control groups (p > 0.05 for all). CONCLUSION: Fetal left ventricular mod-MPI is
      not affected by the presence of an IHF in the fetal left ventricle between 20th
      and 24th gestational weeks and thus it does not need to be assessed in this
      situation.

PMID- 24749804
TI  - Doppler reference values of the fetal vertebral and middle cerebral arteries, at
      19-41 weeks gestation.
AB  - OBJECTIVES: Blood flow to the fetal brain is supplied by two vascular systems:
      the vertebral artery (VA) and the internal carotid artery with its anatomical
      continuation, the middle cerebral artery (ICA/MCA). In this work, our aim was to
      establish consistent reference values for the comparative study of both arterial
      systems. METHODS: The study group consisted of 2323 Doppler examinations of the
      VA, MCA and UA performed on 2323 single pregnancies between 19 and 41 weeks.
      These values were afterwards used to calculate the pulsatility index (PI), peak
      systolic velocity (PSV) and cerebro-placental ratio (CPR) percentiles. RESULTS:
      The VA and MCA PI reached maximum values at the end of the second trimester and
      decreased afterwards due to an increase in the diastolic flow. Conversely, the VA
      and MCA PSV increased progressively until the end of pregnancy. Regarding the VA
      and MCA CPR values, they were higher in the middle of the third trimester and
      decreased afterwards. CONCLUSIONS: In both arterial systems, Doppler reference
      values have been calculated for the PI, PSV and CPR, being available for future
      comparative studies.

PMID- 24749807
TI  - Malignancy and thrombotic microangiopathy or atypical haemolytic and uraemic
      syndrome?

PMID- 24749806
TI  - Enhanced chondrogenic differentiation of dental pulp stem cells using
      nanopatterned PEG-GelMA-HA hydrogels.
AB  - We have examined the effects of surface nanotopography and hyaluronic acid (HA)
      on in vitro chondrogenesis of dental pulp stem cells (DPSCs). Ultraviolet
      assisted capillary force lithography was employed to fabricate well-defined
      nanostructured scaffolds of composite PEG-GelMA-HA hydrogels that consist of
      poly(ethylene glycol) dimethacrylate (PEGDMA), methacrylated gelatin (GelMA), and
      HA. Using this microengineered platform, we first demonstrated that DPSCs formed
      three-dimensional spheroids, which provide an appropriate environment for in
      vitro chondrogenic differentiation. We also found that DPSCs cultured on
      nanopatterned PEG-GelMA-HA scaffolds showed a significant upregulation of the
      chondrogenic gene markers (Sox9, Alkaline phosphatase, Aggrecan, Procollagen type
      II, and Procollagen type X), while downregulating the pluripotent stem cell gene,
      Nanog, and epithelial-mesenchymal genes (Twist, Snail, Slug) compared with tissue
      culture polystyrene-cultured DPSCs. Immunocytochemistry showed more extensive
      deposition of collagen type II in DPSCs cultured on the nanopatterned PEG-GelMA
      HA scaffolds. These findings suggest that nanotopography and HA provide important
      cues for promoting chondrogenic differentiation of DPSCs. 

PMID- 24749808
TI  - American Geriatrics Society/Association of Directors of Geriatric Academic
      Programs curricular milestones for graduating geriatric fellows.
AB  - This article describes the curricular milestones for geriatric fellows and the
      process used to develop them. The curricular milestones were developed to
      determine what every graduating geriatric fellow should be able to demonstrate to
      ensure that they will be able to practice effectively and safely in all care
      settings and with different older adult populations. Three major domains were
      identified: Caring for the Elderly Patient, Systems-Based Care for Elder
      Patients, and Geriatric Syndromes. Six hundred thirty-five geriatricians each
      reviewed and commented on one domain. These geriatricians represented important
      stakeholder groups: geriatric fellowship program directors; Association of
      Directors of Geriatric Academic Programs (ADGAP) members, who are primarily
      geriatric program and fellowship directors; the American Geriatrics Society (AGS)
      and ADGAP Education Committee; the AGS Teacher's Section; Geriatric Academic
      Career Award awardees; and through the American Board of Internal Medicine and
      the American Board of Family Medicine, board-certified geriatricians who spend
      more than 50% of their time in clinical practice. The AGS and ADGAP boards
      approved the final set of 76 Geriatric Curricular Milestones, which were posted
      on the Portal of Geriatric Online Education in December 2012. These curricular
      milestones are intended to assist geriatric fellowship directors as they develop
      curricula and assessments to inform program director reporting to the
      Accreditation Council for Graduate Medical Education in the Next Accreditation
      System, which begins in July 2014. 

PMID- 24749810
TI  - Redox properties of plant biomass-derived black carbon (biochar).
AB  - Soils and sediments worldwide contain appreciable amounts of thermally altered
      organic matter (chars). Chars contain electroactive quinoid functional groups and
      polycondensed aromatic sheets that were recently shown to be of biogeochemical
      and envirotechnical relevance. However, so far no systematic investigation of the
      redox properties of chars formed under different pyrolysis conditions has been
      performed. Here, using mediated electrochemical analysis, we show that chars made
      from different feedstock and over a range of pyrolysis conditions are redox
      active and reversibly accept and donate up to 2 mmol electrons per gram of char.
      The analysis of two thermosequences revealed that chars produced at intermediate
      to high heat treatment temperatures (HTTs) (400-700  degrees C) show the highest
      capacities to accept and donate electrons. Combined electrochemical, elemental,
      and spectroscopic analyses of the thermosequence chars provide evidence that the
      pool of redox-active moieties is dominated by electron-donating, phenolic
      moieties in the low-HTT chars, by newly formed electron accepting quinone
      moieties in intermediate-HTT chars, and by electron accepting quinones and
      possibly condensed aromatics in the high-HTT chars. We propose to consider chars
      in environmental engineering applications that require controlled electron
      transfer reactions. Electroactive char components may also contribute to the
      redox properties of traditionally defined "humic substances". 

PMID- 24749809
TI  - Subfoveal choroidal thickness in patients with chronic heart failure analyzed by
      spectral-domain optical coherence tomography.
AB  - PURPOSE: To evaluate the subfoveal choroidal thickness (SFCT) measured by
      enhanced depth imaging optical coherence tomography (EDI-OCT) in eyes of chronic
      heart failure (CHF) patients. METHODS: Fifty-six patients with CHF and 56 age-
      and gender-matched healthy individuals were enrolled. The SFCT was measured by
      EDI-OCT. The ejection fraction of left ventricle (EFLV), age, intraocular
      pressure (IOP), axial length (AL), systolic and diastolic blood pressure, and
      ocular perfusion pressure (OPP) were also measured. RESULTS: Mean SFCT was 181.2
      +/- 80.23 MUm in the study group and 283.6 +/- 52.4 MUm in the control group (p =
      0.000). There was a statistically significant correlation between the SFCT and
      each of EFLV and age. SFCT value was not statistically significantly associated
      with AL, IOP and OPP. CONCLUSION: Our results suggest that SFCT is lower in eyes
      of CHF patients compared to age- and gender-matched healthy individuals.

PMID- 24749811
TI  - Maternal micronutrients, omega-3 fatty acids, and placental PPARgamma expression.
AB  - An altered one-carbon cycle is known to influence placental and fetal
      development. We hypothesize that deficiency of maternal micronutrients such as
      folic acid and vitamin B12 will lead to increased oxidative stress, reduced long
      chain polyunsaturated fatty acids, and altered expression of peroxisome
      proliferator activated receptor (PPARgamma) in the placenta, and omega-3 fatty
      acid supplementation to these diets will increase the expression of PPARgamma.
      Female rats were divided into 5 groups: control, folic acid deficient, vitamin
      B12 deficient, folic acid deficient + omega-3 fatty acid supplemented, and
      vitamin B12 deficient + omega-3 fatty acid supplemented. Dams were dissected on
      gestational day 20. Maternal micronutrient deficiency leads to lower (p < 0.05)
      levels of placental docosahexaenoic acid, arachidonic acid, PPARgamma expression
      and higher (p < 0.05) levels of plasma malonidialdehyde, placental IL-6, and TNF
      alpha. Omega-3 fatty acid supplementation to a vitamin B12 deficient diet
      normalized the expression of PPARgamma and lowered the levels of placental TNF
      alpha. In the case of supplementation to a folic acid deficient diet it lowered
      the levels of malonidialdehyde and placental IL-6 and TNF-alpha. This study has
      implications for fetal growth as oxidative stress, inflammation, and PPARgamma
      are known to play a key role in the placental development. 

PMID- 24749812
TI  - Itching is a significant problem and a mediator between disease severity and
      quality of life for patients with psoriasis: results from a randomized controlled
      trial.
AB  - BACKGROUND: In patients with moderate-to-severe psoriasis, health-related quality
      of life (HRQOL) has been shown to improve in parallel with improvement in disease
      severity. OBJECTIVES: To evaluate the role of pruritus (itch) in mediating the
      relationship between improvements in disease severity and HRQOL. METHODS: Data
      from a phase 2 clinical trial, in which 142 patients with moderate-to-severe
      plaque psoriasis received ixekizumab or placebo, were used for this posthoc
      analysis. Relationships between improvement in Psoriasis Area and Severity Index
      (PASI), Itch Visual Analogue Scale (VAS) and Dermatology Life Quality Index
      (DLQI), as well as in individual DLQI domains (symptoms and feelings, treatment,
      work and school, daily activities, leisure, and personal relationships) from
      baseline to week 16 were determined. Multiple hierarchical linear regressions and
      Sobel tests were conducted to evaluate the results. RESULTS: Improvement in PASI
      was highly correlated with pruritus improvement and improvements in DLQI total
      and domain scores at week 16 (P < 0.01). Multiple hierarchical linear regression
      analyses showed a statistically significant (P < 0.01) association between
      improvement in pruritus and improvement in DLQI total score and each of the six
      DLQI domain scores after adjusting for improvement in PASI. Sobel tests indicated
      that pruritus had a significant mediation effect (P < 0.05) on the association of
      PASI improvement with improvement in DLQI total score and all domains except the
      personal relationships score. CONCLUSIONS: Pruritus appears to be an important
      mediator of the association between improvements in disease severity and HRQOL in
      patients with moderate-to-severe psoriasis.

PMID- 24749813
TI  - Application of interferon alpha 2b in conjunctival intraepithelial neoplasia:
      predictors and prognostic factors.
AB  - PURPOSE: To test the safety, tolerability, and efficacy of interferon alpha 2b
      for conjunctival intraepithelial neoplasia (CIN) and to evaluate the risk factors
      associated with its clinical outcome. A secondary goal is to identify predictors
      of duration of treatment to achieve good results. METHODS: A prospective,
      noncomparative case series. Twenty-two patients with CIN were treated with
      interferon alpha 2b (1 million IU/mL) 4 times daily. Patients were evaluated by
      slit-lamp biomicroscopy, corneal histopathology, and impression cytology and the
      same physician carried out the diagnosis in all cases. Patients were monitored
      for relapses for 48 months after interferon therapy had ended. The following
      statistical tests were carried out: descriptive, bivariate correlation, and
      survival curves. RESULTS: Topical therapy eliminated clinical signs of disease in
      91% of the cases (20 of 22). The average time to CIN resolution was 3.5 months
      (range 1-9), with only 4 patients presenting adverse effects (1 irritative
      conjunctivitis and 3 punctate keratitis). None of the 4 cases experiencing
      adverse reactions required discontinuation of therapy. Patients living in areas
      with high ultraviolet radiation levels had a longer clinical resolution (4.2
      months) than those living in areas with low UV levels (1.8 months, P=0.01). There
      was association with statistical significance between the size of the lesion at
      the third month and treatment duration (P=0.048). CONCLUSION: Topical interferon
      alpha 2b is an effective and safe treatment option for CIN. The place of
      residence can be a risk factor; areas like coast with higher UV levels result in
      a slower clinical resolution than inland areas. The size of the lesion after the
      third month of treatment with interferon can be a predictor of time to clinical
      resolution of CIN.

PMID- 24749814
TI  - High-performance chemical sensing using Schottky-contacted chemical vapor
      deposition grown monolayer MoS2 transistors.
AB  - Trace chemical detection is important for a wide range of practical applications.
      Recently emerged two-dimensional (2D) crystals offer unique advantages as
      potential sensing materials with high sensitivity, owing to their very high
      surface-to-bulk atom ratios and semiconducting properties. Here, we report the
      first use of Schottky-contacted chemical vapor deposition grown monolayer MoS2 as
      high-performance room temperature chemical sensors. The Schottky-contacted MoS2
      transistors show current changes by 2-3 orders of magnitude upon exposure to very
      low concentrations of NO2 and NH3. Specifically, the MoS2 sensors show clear
      detection of NO2 and NH3 down to 20 ppb and 1 ppm, respectively. We attribute the
      observed high sensitivity to both well-known charger transfer mechanism and, more
      importantly, the Schottky barrier modulation upon analyte molecule adsorption,
      the latter of which is made possible by the Schottky contacts in the transistors
      and is not reported previously for MoS2 sensors. This study shows the potential
      of 2D semiconductors as high-performance sensors and also benefits the
      fundamental studies of interfacial phenomena and interactions between chemical
      species and monolayer 2D semiconductors. 

PMID- 24749815
TI  - Multisystemic therapy for disruptive behavior problems in youths with autism
      spectrum disorders: a progress report.
AB  - Youths with autism spectrum disorders (ASD) often engage in serious disruptive
      behaviors that interfere with their ability to successfully manage day-to-day
      responsibilities and contribute to relationship problems with caregivers, peers,
      and teachers. Effective treatments are needed to address the factors linked with
      disruptive behavior problems in this population of youths. Multisystemic therapy
      (MST) is a comprehensive family- and community-based treatment approach that has
      been effective with other difficult-to-treat populations of youths and holds
      promise for youths with ASD. In this article, we review the broad range of
      factors associated with disruptive behaviors among youths with ASD and discuss
      how MST interventions can be adapted to address those factors. We also present a
      framework for our adaptation of the MST model for youths with ASD. This framework
      includes a recently completed pilot study as well as an ongoing efficacy trial
      that together have served to identify key interventions for our adaptation of the
      MST model. 

PMID- 24749817
TI  - Toward a greater understanding of the emotional dynamics of the mortality
      salience manipulation: revisiting the "affect-free" claim of terror management
      research.
AB  - The experimental manipulation of mortality salience (MS) represents one of the
      most widely used methodological procedures in social psychology, having been
      employed by terror management researchers in hundreds of studies over the last 20
      years. One of the more provocative conclusions regarding this task is that it
      does not produce any reliable changes in self-reported affect, a view that we
      refer to as the affect-free claim. After reviewing 336 published studies that
      used the standard version of the MS task, we suggest that the evidence on which
      this claim is based may be less definitive than is commonly supposed. Moreover,
      we propose that the MS manipulation can, in fact, produce significant and
      meaningful changes in affect once one employs the appropriate measures and
      experimental design. In support of this position, we report 4 experiments, each
      of which demonstrates reliable activation of negative affect, especially with
      respect to fear-/terror-related sentiments. We discuss the implications of our
      findings for terror management theory as well as for research and theory on the
      measurement of mood and emotion.

PMID- 24749816
TI  - Role of cathepsin B in regulating migration and invasion of fibroblast-like
      synoviocytes into inflamed tissue from patients with rheumatoid arthritis.
AB  - Cathepsin B (CB), an important proteinase that participates in joint destruction
      in rheumatoid arthritis (RA), exhibits higher expression in fibroblast-like
      synoviocyte (FLS) of abnormal proliferative synovial tissues. Whether and how it
      affects the biological behaviours of RA-FLS, such as migration and invasion, are
      poorly understood. In the present study, CB expression in synovial tissues of
      patients with RA and ostearthritis (OA) were measured by quantitative polymerase
      chain reaction (qPCR) and immunohistochemistry (IHC), respectively. Stable
      depletion of endogenous CB was achieved by small interfering RNA (siRNA)
      transfection, and decrease of CB activity was acquired by using its specific
      inhibitor (CA074Me). The effects of CA074Me and RNA interference (RNAi)
      treatments on proliferation, migration, invasion, matrix metalloproteinase (MMP)
      2/-9 expression, focal adhesion kinase (FAK) activation, and mitogen-activated
      protein kinases (MAPKs) phosphorylation of FLS were analysed. In RA synovial
      tissues, CB was expressed at elevated levels compared with OA synovial tissues.
      CA074Me could inhibit invasion of FLS obtained from RA patients in an ex-vivo
      invasion model. CA074Me and siRNA treatments suppressed the migration and
      invasion of FLS, reduced the activity, expression and mRNA level of MMP-2,
      restrained the activation of FAK and reduced the expression of F-actin. Moreover,
      CA074Me decreased the phosphorylation of P38 MAPK and c-Jun N-terminal kinase
      (JNK) in FLS, while siCB treatment reduced the phosphorylation of P38 but not
      JNK. CB substantially contributes to the invasive phenotype of FLS that leads to
      joint destruction in RA. This proteinase may show promise as a therapeutic target
      in inflammatory arthritis. 

PMID- 24749818
TI  - The college journey and academic engagement: how metaphor use enhances identity
      based motivation.
AB  - People commonly talk about goals metaphorically as destinations on physical paths
      extending into the future or as contained in future periods. Does metaphor use
      have consequences for people's motivation to engage in goal-directed action?
      Three experiments examine the effect of metaphor use on students' engagement with
      their academic possible identity: their image of themselves as academically
      successful graduates. Students primed to frame their academic possible identity
      using the goal-as-journey metaphor reported stronger academic intention, and
      displayed increased effort on academic tasks, compared to students primed with a
      nonacademic possible identity, a different metaphoric framing (goal-as-contained
      entity), and past academic achievements (Studies 1-2). This motivating effect
      persisted up to a week later as reflected in final exam performance (Study 3).
      Four experiments examine the cognitive processes underlying this effect.
      Conceptual metaphor theory posits that an accessible metaphor transfers knowledge
      between dissimilar concepts. As predicted in this paradigm, a journey-metaphoric
      framing of a possible academic identity transferred confidence in the procedure,
      or action sequence, required to attain that possible identity, which in turn led
      participants to perceive that possible identity as more connected to their
      current identity (Study 4). Drawing on identity-based motivation theory, we
      hypothesized that strengthened current/possible identity connection would mediate
      the journey framing's motivating effect. This mediational process predicted
      students' academic engagement (Study 5) and an online sample's engagement with
      possible identities in other domains (Study 6). Also as predicted, journey
      framing increased academic engagement particularly among students reporting a
      weak connection to their academic possible identity (Study 7).

PMID- 24749819
TI  - Approach aversion: negative hedonic reactions toward approaching stimuli.
AB  - We live in a dynamic world, surrounded by moving stimuli-moving people, moving
      objects, and moving events. The current research proposes and finds an approach
      aversion effect-individuals feel less positively (or more negatively) about a
      stimulus if they perceive it to be approaching rather than receding or static.
      The effect appears general, occurring whether the stimulus is initially negative
      or nonnegative and whether it moves in space (toward or away from "here"), in
      time (toward or away from "now"), or in probability (toward or away from "sure").
      This research complements extensive existing research on perceived static
      distance of stimuli (near vs. far) by exploring perceived dynamic movement of
      stimuli (approaching vs. receding), showing that the effect of movement is
      distinct from the effect of distance.

PMID- 24749820
TI  - Contemplating the ultimate sacrifice: identity fusion channels pro-group affect,
      cognition, and moral decision making.
AB  - Although most people acknowledge the moral virtue in sacrificing oneself to save
      others, few actually endorse self-sacrifice. Seven experiments explored the
      cognitive and emotional mechanisms that underlie such endorsements. Participants
      responded to 1 of 2 moral dilemmas in which they could save 5 members of their
      country only by sacrificing themselves. Over 90% of participants acknowledged
      that the moral course of action was to sacrifice oneself to save others
      (Experiment 1), yet only those who were strongly fused with the group
      preferentially endorsed self-sacrifice (Experiments 2-7). The presence of a
      concern with saving group members rather than the absence of a concern with self
      preservation motivated strongly fused participants to endorse sacrificing
      themselves for the group (Experiment 3). Analyses of think aloud protocols
      suggested that saving others was motivated by emotional engagement with the group
      among strongly fused participants but by utilitarian concerns among weakly fused
      participants (Experiment 4). Hurrying participants' responses increased self
      sacrifice among strongly fused participants but decreased self-sacrifice among
      weakly fused participants (Experiment 5). Priming the personal self increased
      endorsement of self-sacrifice among strongly fused participants but further
      reduced endorsement of self-sacrifice among weakly fused participants (Experiment
      6). Strongly fused participants ignored utilitarian considerations, but weakly
      fused persons endorsed self-sacrifice more when it would save more people
      (Experiment 7). Apparently, the emotional engagement with the group experienced
      by strongly fused persons overrides the desire for self-preservation and compels
      them to translate their moral beliefs into self-sacrificial behavior.

PMID- 24749821
TI  - Responses to social exclusion in cultural context: evidence from farming and
      herding communities.
AB  - In a series of studies, we investigated the role of economic structures (farming
      vs. herding) and source of ostracism (close other vs. stranger) in social
      exclusion experiences. We first confirmed that herders rely on strangers to a
      greater extent than do farmers for economic success (validation study). Next, we
      verified that farmers and herders understand the concept of ostracism, and its
      emotional consequences, in similar ways (Study 1). The studies that followed
      provided converging evidence that cultural group membership shapes sensitivity
      and responses to social exclusion. Using different methodologies, in Studies 2
      and 3, we showed that, whereas the psychological consequences of ostracism by
      close others are similar for farmers and herders, herders are more strongly
      affected by ostracism from strangers. The last two studies demonstrated that
      herders recommend more affiliative responses to ostracism by strangers than do
      farmers both to those involved in the ostracism event (Study 4) and to naive
      individuals (Study 5). Moreover, Study 5 revealed that the amount of time spent
      with strangers mediated cultural group differences in the extent to which
      affiliative and aggressive actions are recommended following social exclusion by
      strangers. Taken together, these results demonstrate that the economic systems on
      which communities are based shape how their members interact with others and that
      this, in turn, can shape individuals' responses to social exclusion.

PMID- 24749822
TI  - Moral actor, selfish agent.
AB  - People are motivated to behave selfishly while appearing moral. This tension
      gives rise to 2 divergently motivated selves. The actor-the watched self-tends to
      be moral; the agent-the self as executor-tends to be selfish. Three studies
      present direct evidence of the actor's and agent's distinct motives. To recruit
      the self-as-actor, we asked people to rate the importance of various goals. To
      recruit the self-as-agent, we asked people to describe their goals verbally. In
      Study 1, actors claimed their goals were equally about helping the self and
      others (viz., moral); agents claimed their goals were primarily about helping the
      self (viz., selfish). This disparity was evident in both individualist and
      collectivist cultures, attesting to the universality of the selfish agent. Study
      2 compared actors' and agents' motives to those of people role-playing highly
      prosocial or selfish exemplars. In content (Study 2a) and in the impressions they
      made on an outside observer (Study 2b), actors' motives were similar to those of
      the prosocial role-players, whereas agents' motives were similar to those of the
      selfish role-players. Study 3 accounted for the difference between the actor and
      agent: Participants claimed that their agent's motives were the more realistic
      and that their actor's motives were the more idealistic. The selfish agent/moral
      actor duality may account for why implicit and explicit measures of the same
      construct diverge, and why feeling watched brings out the better angels of human
      nature.

PMID- 24749823
TI  - To have or to learn? The effects of materialism on British and Chinese children's
      learning.
AB  - This article presents a systematic attempt to examine the associations of
      materialism with learning in 9- to 11-year-old children in 2 countries of similar
      economic development but different cultural heritage. Using cross-sectional,
      longitudinal, and experimental methods, we test a theoretically driven model of
      associations among materialism, learning motivations, and learning outcomes.
      Convergent findings suggest that a materialist orientation in elementary school
      children lowers intrinsic learning motivations, fosters extrinsic learning
      motivations, and leads to poorer learning outcomes. Materialism was linked
      directly to lower exam performance, and this link was mediated by lower mastery
      and heightened performance goals, with patterns not differing between British and
      Hong Kong Chinese children (Study 1). A follow-up showed that initial materialism
      predicted worse exam grades 1 year later, suggesting a detrimental long-term
      effect on Chinese children's school performance (Study 2). We then tested
      relationships between materialism and learning experimentally, by priming a
      momentary (state) orientation toward materialism. Writing about material
      possessions and money affected Chinese children's learning motivations, so that
      they endorsed lower mastery and higher performance goals (Study 3). A video-diary
      materialism prime had significant effects on actual learning behaviors, leading
      British children to (a) choose a performance-oriented learning task over a
      mastery-oriented task and (b) give up on the task more quickly (Study 4). This
      research has important implications for personality psychology, educational
      policy, and future research.

PMID- 24749824
TI  - When sex goes wrong: a behavioral systems perspective on individual differences
      in sexual attitudes, motives, feelings, and behaviors.
AB  - In the research program summarized here, we adopted a behavioral systems approach
      to explain individual differences in human sexual behavior. In the 1st stage, we
      developed the Sexual System Functioning Scale (SSFS)-a self-report instrument for
      assessing hyperactivation and deactivation of the sexual system. Sexual
      hyperactivation involves intense but anxious expressions of sexual desire,
      whereas sexual deactivation includes inhibition of sexual inclinations. In
      subsequent stages, we administered the SFSS to 18 samples to determine its
      structural, convergent, discriminant, and predictive validity as well as its
      nomological network. We found that SSFS deactivation and hyperactivation scores
      are meaningfully associated with existing measures of sexual attitudes, motives,
      feelings, and behaviors and with measures of personal and interpersonal well
      being. Moreover, the scores predict cognitive, affective, physiological, and
      behavioral responses to sexual stimuli. Implications of our findings for
      understanding the potential of sex for both joy and distress are discussed.

PMID- 24749825
TI  - Influences of gender identity on children's maltreatment of gender-nonconforming
      peers: a person * target analysis of aggression.
AB  - We investigated whether gender identity influences preadolescents' tendency to
      single out gender-atypical peers for abuse. Data were gathered from 195 boys and
      girls (M age = 10.1 years) in the fall and spring of a school year. Children self
      reported multiple dimensions of gender identity (intergroup bias, felt pressure
      for gender differentiation, felt gender typicality, gender contentedness); peers
      assessed each other's social behavior (gender nonconformity, aggression toward
      each classmate). Using multilevel modeling, we examined how children's attacks on
      gender-nonconforming peers (relative to their attacks on other peers) changed
      over the school year depending on their gender identity. There was modest support
      for the hypothesis that overconfident, arrogant gender identity promotes abuse of
      gender-atypical peers but considerable support for the hypothesis that insecure,
      self-questioning gender identity fosters this tendency. Implications for issues
      central to contemporary personality theory (e.g., Person * Situation interaction)
      are discussed. New and somewhat surprising information about the cognitive and
      behavioral characteristics of gender-nonconforming preadolescents is provided.

PMID- 24749826
TI  - 'Bourdieu', medical elites and 'social class': a qualitative study of 'desert
      island' doctors.
AB  - Sociologists of professions draw on Weberian theories of closure. However they
      have tended to ignore Bourdieu's work, which rejects Weberian notions of class
      and status groups as distinct ideal types and sees these concepts as inextricably
      linked. Bourdieu emphasises the importance of a class-based habitus which
      generates orientations, inclinations and dispositions that organise practices and
      the perception of practice. For Bourdieu, because individuals perceive one
      another primarily through the status that attaches to their practices (through a
      symbolic veil of honour) they fail to perceive the real basis of these practices:
      the forms of capital that underlie the different habitus and enable their
      realisation. This article draws on interviews with 17 elite doctors appearing on
      a national (UK) radio show during which they choose eight discs to take to a
      desert island. According to Bourdieu, 'nothing more clearly affirms one's
      "class", nothing more infallibly classifies, than one's taste in music'. An
      analysis of the doctors' musical tastes and their mode of acquisition (largely,
      for these elites, via their family and education at independent schools), as well
      as other insights into their cultural capital reveals the importance of linking
      class and status when exploring professional status and prestige. 

PMID- 24749827
TI  - Totally intracorporeal replacement of the ureter using whole-mount ileum.
AB  - Ileal ureter is a suitable treatment option for patients with long ureteral
      strictures. Minimally invasive techniques have been shown to be as safe as open
      technique and superior in terms of postoperative recovery. We report the first
      case of laparoscopic totally intracorporeal replacement of ureter using whole
      mount ileum in a patient with right-sided long ureteral stricture. The operative
      time was 150 minutes, and there were no complications. We have demonstrated the
      safety and feasibility of laparoscopic intracorporeal ileal ureter with possible
      advantage of shorter operative time compared with the robotic-assisted technique
      reported recently.

PMID- 24749828
TI  - Review article: the biology, diagnosis and management of gastrointestinal stromal
      tumours.
AB  - BACKGROUND: Gastrointestinal stromal tumours (GIST) are the most common
      mesenchymal tumours of the gastrointestinal tract with an increasing incidence.
      AIMS: To review the biology, diagnosis and treatment of gastrointestinal stromal
      tumours. METHODS: A PubMed search using the phrases 'Gastrointestinal stromal
      tumor', 'imatinib', 'c-kit'. RESULTS: The diagnosis of GIST is established by
      histology supplemented by the immunohistochemical marker CD117, which is positive
      in 95% of cases. The most common site of the tumour is the stomach. Most GIST are
      benign with 20-30% malignant. Five-year survival for malignant GIST ranges
      between 35% and 65% and depends primarily on tumour size, mitotic index and
      location. The malignant behaviour of GIST is best assessed by invasion of
      adjacent structures and distant metastases. The gold standard for treatment is
      surgical resection. Imatinib, a tyrosine kinase inhibitor, is the primary therapy
      for unresectable, recurrent or metastatic disease. CONCLUSIONS: Gastrointestinal
      stromal tumours are rare tumours of the gastrointestinal tract and they vary in
      presentation. When surgical resection is not achievable, imatinib is the
      treatment of choice.

PMID- 24749829
TI  - Interexaminer reproducibility of optical coherence tomography for measuring the
      tear film meniscus.
AB  - PURPOSE: New optical coherence tomography (OCT) devices with anterior segment
      module are able to measure the tear meniscus height (TMH) and tear meniscus area
      (TMA). Since the borders of the area and the height are to be marked by an
      examiner, the measurements are prone to be subjective. Herein, we aimed to
      evaluate the interexaminer reproducibility of the tear meniscus measurements with
      OCT. MATERIALS AND METHODS: In this prospective cross-sectional study, both eyes
      of 300 consecutive patients with and without dry eye were studied. Following
      routine ophthalmologic examination, tear-film OCT images were obtained. Two
      examiners, who were unaware of the other examiner's results, measured the TMH
      (i.e. the line connecting the intersection of the meniscus with the cornea/sclera
      and eyelid) and cross-sectional TMA. The reliability and correlation of the two
      examiners' results were assessed. RESULTS: Four right and six left eyes were
      excluded from the final analysis, so a total of 590 eyes were evaluated. The mean
      difference of the two examiners' measurements of both eyes was -0.001 +/- 0.027
      mm(2) in TMA, and -21.29 +/- 39.95 MUm in TMH. An agreement between the two
      examiners was found regarding TMA and TMH measurements for right and left, as
      well as both eyes (Cronbach's alpha > 0.900, for all). Also, the correlation
      between both variables was high (inter item correlation matrix > 0.840, for all).
      CONCLUSIONS: We showed a strong statistical agreement for both TMA and TMH
      measurements. According to our results, we believe that FD-OCT device is
      dependable in measuring the TMA and TMH values, given that its results are
      reproducible.

PMID- 24749830
TI  - Antiviral effects of persimmon extract on human norovirus and its surrogate,
      bacteriophage MS2.
AB  - Human noroviruses (NoVs) are the leading cause of gastroenteritis and foodborne
      illnesses worldwide. In this study, we investigated the effects of persimmon
      extract (PE) on NoV GII.4 and bacteriophage MS2. We also examined the
      relationship between the tannin content of PE and its antiviral effects to
      identify the active ingredient in PE. Different persimmon tannin (PT) solutions
      were prepared by mixing PE with different concentrations of bovine serum albumin.
      The antiviral efficacy of these solutions against NoV was evaluated by
      quantifying the amount of residual noroviral genome using a quantitative reverse
      transcription PCR (qRT-PCR) assay. The antiviral efficacy of PE against MS2 was
      examined with an infectivity assay (plaque assay). Solutions containing >= 0.11
      mg/mL PT reduced the noroviral genome by more than 70.0% and the infectivity of
      MS2 by more than 2.5 log PFU/mL. However, the effects of PT on both viruses
      decreased markedly at a concentration of 0.08 mg/mL and solutions containing
      negligible PT had no antiviral activity. These results suggest that the PT
      component of PE inactivates NoV and MS2. Our results indicate that PE is a
      nontoxic antiviral agent effective against enteric viruses. PRACTICAL
      APPLICATION: Persimmon extract showed antiviral effects against NoV and
      bacteriophage MS2. Persimmon extract is suitable for use as an antiviral agent.

PMID- 24749831
TI  - Dispersal propensity in Tetrahymena thermophila ciliates - a reaction norm
      perspective.
AB  - Dispersal and phenotypic plasticity are two main ways for species to deal with
      rapid changes of their environments. Understanding how genotypes (G),
      environments (E), and their interaction (genotype and environment; G * E) each
      affects dispersal propensity is therefore instrumental for predicting the
      ecological and evolutionary responses of species under global change. Here we
      used an actively dispersing ciliate to quantify the contributions of G, E, and G
      * E on dispersal propensity, exposing 44 different genotypes to three different
      environmental contexts (densities in isogenotype populations). Moreover, we
      assessed the condition dependence of dispersal, that is, whether dispersal is
      related to morphological, physiological, or behavioral traits. We found that
      genotypes showed marked differences in dispersal propensity and that dispersal is
      plastically adjusted to density, with the overall trend for genotypes to exhibit
      negative density-dependent dispersal. A small, but significant G * E interaction
      indicates genetic variability in plasticity and therefore some potential for
      dispersal plasticity to evolve. We also show evidence consistent with condition
      dependent dispersal suggesting that genotypes also vary in how individual
      condition is linked to dispersal under different environmental contexts thereby
      generating complex dispersal behavior due to only three variables (genes,
      environment, and individual condition). 

PMID- 24749833
TI  - Large thermoelectricity via variable range hopping in chemical vapor deposition
      grown single-layer MoS2.
AB  - Ultrathin layers of semiconducting molybdenum disulfide (MoS2) offer significant
      prospects in future electronic and optoelectronic applications. Although an
      increasing number of experiments bring light into the electronic transport
      properties of these crystals, their thermoelectric properties are much less
      known. In particular, thermoelectricity in chemical vapor deposition grown MoS2,
      which is more practical for wafer-scale applications, still remains unexplored.
      Here, for the first time, we investigate these properties in grown single layer
      MoS2. Microfabricated heaters and thermometers are used to measure both
      electrical conductivity and thermopower. Large values of up to ~30 mV/K at room
      temperature are observed, which are much larger than those observed in other two
      dimensional crystals and bulk MoS2. The thermopower is strongly dependent on
      temperature and applied gate voltage with a large enhancement at the vicinity of
      the conduction band edge. We also show that the Seebeck coefficient follows S ~
      T(1/3), suggesting a two-dimensional variable range hopping mechanism in the
      system, which is consistent with electrical transport measurements. Our results
      help to understand the physics behind the electrical and thermal transports in
      MoS2 and the high thermopower value is of interest to future thermoelectronic
      research and application. 

PMID- 24749832
TI  - "Click" immobilization of a VEGF-mimetic peptide on decellularized endothelial
      extracellular matrix to enhance angiogenesis.
AB  - We show that coating of decellularized extracellular matrix (DC-ECM) on substrate
      surfaces is an efficient way to generate a platform mimicking the native ECM
      environment. Moreover, the DC-ECM can be modified with a peptide (QK) mimicking
      vascular endothelial growth factor without apparently compromising its integrity.
      The modification was achieved through metabolic incorporation of a "clickable"
      handle to DC-ECM followed by rapid attachment of the QK peptide with an azido tag
      using copper-catalyzed click reaction. The attachment of the QK peptide on to DC
      ECM in this way further enhanced the angiogenic responses (formation of branched
      tubular networks) of endothelial cells.

PMID- 24749834
TI  - A mathematical approach to estimate the efficacy of individual-donation and
      minipool nucleic acid amplification test options in preventing transmission risk
      by window period and occult hepatitis B virus infections.
AB  - BACKGROUND: Sensitivity data from a head-to-head comparison study in South Africa
      were used to compare the efficacy of the Ultrio Plus assay in individual-donation
      (ID) and minipool (MP)4 and MP8 formats with that of TaqScreen MP6 in preventing
      hepatitis B virus (HBV) transmission risk. STUDY DESIGN AND METHODS: The
      replicate nucleic acid test (NAT) results on 106 HBV NAT (Ultrio)-yield samples
      and 29 HBV DNA (Ultrio)-negative, hepatitis B surface antigen (HBsAg)-positive
      samples were used to determine the viral load in copies/mL against the Eurohep
      HBV standard by probit analysis. Random viral load distributions were established
      in 32 pre-HBsAg window period (WP), 15 post-HBsAg WP, and 56 occult HBV infection
      (OBI) donations. Regression analysis of log viral load and Poisson distribution
      statistics of infectious HBV particles in blood components was used to predict
      infectivity and efficacy of NAT options in removing HBV transmission risk.
      RESULTS: For red blood cell transfusions (20 mL of plasma), the modeling
      predicted an Ultrio Plus ID-NAT efficacy of 68 and 83% in removing WP and
      (antibody to hepatitis B surface antigen-negative) OBI transmission risk,
      respectively, compared to 52 and 49% by TaqScreen MP6. For 200 mL of fresh-frozen
      plasma the estimated efficacy levels by these ID- and MP6-NAT options reduced to
      57 and 44% for WP and to 67 and 34% for OBI donations, respectively. CONCLUSION:
      The efficacy of the currently available commercial NAT systems in reducing HBV
      transmission risk is mainly driven by the pool size and the transfusion plasma
      volume. The modeled OBI transmission risk and NAT efficacy levels were in line
      with those recently reported in three lookback studies and give more insight in
      the incremental safety provided by HBsAg and antibody to hepatitis B core antigen
      testing of ID-NAT screened blood.

PMID- 24749835
TI  - Discovery of daclatasvir, a pan-genotypic hepatitis C virus NS5A replication
      complex inhibitor with potent clinical effect.
AB  - The discovery and development of the first-in-class hepatitis C virus (HCV) NS5A
      replication complex inhibitor daclatasvir (6) provides a compelling example of
      the power of phenotypic screening to identify leads engaging novel targets in
      mechanistically unique ways. HCV NS5A replication complex inhibitors are pan
      genotypic in spectrum, and this mechanistic class provides the most potent HCV
      inhibitors in vitro that have been described to date. Clinical trials with 6
      demonstrated a potent effect on reducing plasma viral load and, in combination
      with mechanistically orthogonal HCV inhibitors, established the ability to cure
      even the most difficult infections without the need for immune stimulation. In
      this Drug Annotation, we describe the discovery of the original high-throughput
      screening lead 7 and the chemical conundrum and challenges resolved in optimizing
      to 6 as a clinical candidate and finally we summarize the results of select
      clinical studies.

PMID- 24749836
TI  - Computer-based first-principles kinetic modeling of degradation pathways and
      byproduct fates in aqueous-phase advanced oxidation processes.
AB  - In this study, a computer-based first-principles kinetic model is developed to
      predict the degradation mechanisms and fates of intermediates and byproducts
      produced during aqueous-phase advanced oxidation processes (AOPs) for various
      organic compounds. The model contains a rule-based pathway generator to generate
      the reaction pathways, a reaction rate constant estimator to estimate the
      reaction rate constant for each reaction generated, a mechanistic reduction
      module to reduce the generated mechanisms, an ordinary differential equations
      generator and solver to solve the generated mechanisms and calculate the
      concentration profiles for all species, and a toxicity estimator to estimate the
      toxicity of major species and calculate time-dependent profiles of relative
      toxicity (i.e., concentration of species divided by toxicity value). We predict
      concentration profiles of acetone and trichloroethylene and their intermediates
      and byproducts in photolysis with hydrogen peroxide (i.e., UV/H2O2) and validate
      with experimental observations. The predicted concentration profiles for both
      parent compounds are consistent with experimental data. The calculated profiles
      of 96-h green algae chronic toxicity show that the overall toxicity decreases
      during the degradation process. These generated mechanisms also provide detailed
      and quantitative insights into the pathways for the formation and consumption of
      important intermediates and byproducts produced during AOPs. Our approach is
      sufficiently general to be applied to a wide range of contaminants. 

PMID- 24749837
TI  - Cannabis for symptom control #279.

PMID- 24749838
TI  - Implementation of multi-family psychoeducational psychotherapy for childhood mood
      disorders in an outpatient community setting.
AB  - Despite advances in evidence-based treatments (EBTs), research suggests these
      interventions are not utilized in practice settings. This study examined
      implementation of multi-family psychoeducational psychotherapy (MF-PEP), an EBT
      for childhood mood disorders, in two outpatient community clinics. Fifteen
      community therapists facilitated MF-PEP. Twenty community clinicians referred 40
      children ages 8-12 with mood disorders and their parents who participated in MF
      PEP. Preliminary descriptive findings based on observations and self-report
      questionnaires demonstrated implementation outcomes of acceptability, adoption,
      appropriateness, feasibility, implementation cost, penetration, and
      sustainability of MF-PEP at these clinics. Parents also demonstrated significant
      improvement in knowledge of mood disorders posttreatment. Preliminary results
      support implementation of MF-PEP in practice settings and suggest community-based
      MF-PEP may be associated with improvement in clinical outcomes. 

PMID- 24749839
TI  - Long-term follow-up and second malignancies in 487 patients with hairy cell
      leukaemia.
AB  - A large, multicentre, retrospective survey of patients with hairy cell leukaemia
      (HCL) was conducted in France to determine the frequency of second malignancies
      and to analyse the long-term effects of the established purine nucleoside
      analogues (PNAs), cladribine and pentostatin. The survey retrospectively reviewed
      the medical history of patients and their immediate family, clinical and
      biological presentation at the time of HCL diagnosis, treatment choice, response
      to treatment, time to relapse and cause of death. Data were collected for 487
      patients with HCL. Of the patients included in the survey, 18% (88/487) had a
      familial history of cancers, 8% (41/487) presented with malignancies before HCL
      diagnosis and 10% (48/487) developed second malignancies after HCL was diagnosed.
      An excess incidence of second malignancies was observed, with a standardized
      incidence ratio (SIR) of 1.86 (95% confidence interval (CI): 1.34-2.51), with no
      significant difference between PNAs. For second haematological malignancies
      alone, the SIR was markedly increased at 5.32 (95% CI: 2.90-8.92). This study
      highlights the high frequency of cancers in HCL patients and their family
      members. The frequency of second malignancies is notably increased, particularly
      for haematological malignancies. The respective role of pentostatin and
      cladribine in the development of second malignancies is debatable. 

PMID- 24749840
TI  - Pharmacotherapy of Hodgkin lymphoma: standard approaches and future perspectives.
AB  - INTRODUCTION: Hodgkin lymphoma (HL) is a lymphoid malignancy with an incidence of
      2 - 3/100,000/year. Young adults are most often affected. Due to the development
      of highly active multi-agent chemotherapy protocols and the optimization of
      radiotherapy (RT) fields and doses, HL has become one of the malignancies with
      the highest cure rates. As treatment efficacy can hardly be improved, the major
      goal of clinical HL research consists in decreasing therapy-associated acute and
      long-term toxicity. To this end, treatment stratification based on interim
      positron emission tomography and the implementation of targeted drugs such as the
      antibody-drug conjugate brentuximab vedotin are currently being evaluated in
      prospective trials. AREAS COVERED: This article reviews recent randomized Phase
      III and larger Phase II trials including HL patients. EXPERT OPINION: In early
      stage HL, excellent results are achieved with a brief chemotherapy followed by
      involved-field RT. Patients with advanced HL should receive six to eight cycles
      of chemotherapy optionally followed by localized RT. In relapsed disease, high
      dose chemotherapy followed by autologous stem cell transplantation represents the
      standard of care for most patients. The use of novel drugs and imaging tools that
      currently undergo evaluation may optimize HL treatment.

PMID- 24749841
TI  - Proceedings from the 2013 Canadian Nutrition Society Conference on Advances in
      Dietary Fats and Nutrition.
AB  - The science of lipid research continues to rapidly evolve and change. New
      knowledge enhances our understanding and perspectives on the role of lipids in
      health and nutrition. However, new knowledge also challenges currently held
      opinions. The following are the proceedings of the 2013 Canadian Nutrition
      Society Conference on the Advances in Dietary Fats and Nutrition. Content experts
      presented state-of-the-art information regarding our understanding of fish oil
      and plant-based n-3 polyunsaturated fatty acids, nutrigenomics, pediatrics,
      regulatory affairs, and trans fats. These important contributions aim to provide
      clarity on the latest advances and opinions regarding the role of different types
      of fats in health. 

PMID- 24749842
TI  - Increased arterial stiffness is independently associated with metabolic syndrome
      and damage index in systemic lupus erythematosus patients: comment on the article
      by Valero-Gonzalez et al.

PMID- 24749843
TI  - Cost-effectiveness of topical imiquimod and fluorouracil vs. photodynamic therapy
      for treatment of superficial basal-cell carcinoma.
AB  - BACKGROUND: A recent noninferiority randomized trial showed that in terms of
      clinical effectiveness imiquimod was superior and topical fluorouracil
      noninferior to methylaminolaevulinate photodynamic therapy (MAL-PDT) for
      treatment of superficial basal-cell carcinoma (sBCC). Although it was expected
      that MAL-PDT would be more costly than either cream, a full cost-effectiveness
      analysis is necessary to determine the balance between effectiveness and costs.
      OBJECTIVE: To determine whether imiquimod or topical fluorouracil are cost
      effective treatments for sBCC compared with MAL-PDT. METHODS: An economic
      evaluation was performed from a healthcare perspective. Data on resource use and
      costs were collected alongside the randomized clinical trial. The incremental
      cost-effectiveness ratio was expressed as the incremental costs per additional
      patient free of tumour recurrence. RESULTS: At 12 months follow-up, the total
      mean costs for MAL-PDT were ?680, for imiquimod cream ?526 and for topical
      fluorouracil cream ?388. Both imiquimod and topical fluorouracil were cost
      effective treatments compared with MAL-PDT. Comparing costs and effectiveness of
      both creams led to a incremental investment of ?4451 to achieve an additional
      patient free of tumour recurrence. The acceptability curve showed that, for a
      threshold value of ?4451, the probability of imiquimod being more cost-effective
      than topical fluorouracil was 50%. CONCLUSION: Based on the 12 months follow-up
      results, imiquimod and topical fluorouracil cream are more cost-effective than
      MAL-PDT for treatment of sBCC. Hence, substituting MAL-PDT with either imiquimod
      or topical fluorouracil results in cost savings; these savings will be larger for
      topical fluorouracil. Long-term follow-up effectiveness data are necessary to
      confirm the cost-effectiveness of imiquimod vs. topical 5-fluorouracil cream.

PMID- 24749844
TI  - Effects of pathogen reduction systems on platelet microRNAs, mRNAs, activation,
      and function.
AB  - Pathogen reduction (PR) systems for platelets, based on chemically induced cross
      linking and inactivation of nucleic acids, potentially prevent transfusion
      transmission of infectious agents, but can increase clinically significant
      bleeding in some clinical studies. Here, we documented the effects of PR systems
      on microRNA and mRNA levels of platelets stored in the blood bank, and assessed
      their impact on platelet activation and function. Unlike platelets subjected to
      gamma irradiation or stored in additive solution, platelets treated with
      Intercept (amotosalen+ ultraviolet-A [UVA] light) exhibited significantly reduced
      levels of 6 of the 11 microRNAs, and 2 of the 3 anti-apoptotic mRNAs (Bcl-xl and
      Clusterin) that we monitored, compared with platelets stored in plasma. Mirasol
      (riboflavin+ UVB light) treatment of platelets did not produce these effects. PR
      neither affected platelet microRNA synthesis or function nor induced cross
      linking of microRNA-sized endogenous platelet RNA species. However, the reduction
      in the platelet microRNA levels induced by Intercept correlated with the platelet
      activation (p < 0.05) and an impaired platelet aggregation response to ADP (p <
      0.05). These results suggest that Intercept treatment may induce platelet
      activation, resulting in the release of microRNAs and mRNAs from platelets. The
      clinical implications of this reduction in platelet nucleic acids secondary to
      Intercept remain to be established.

PMID- 24749846
TI  - What is a geriatrician? American Geriatrics Society and Association of Directors
      of Geriatric Academic Programs end-of-training entrustable professional
      activities for geriatric medicine.
AB  - Entrustable professional activities (EPAs) describe the core work that
      constitutes a discipline's specific expertise and provide the framework for
      faculty to perform meaningful assessment of geriatric fellows. This article
      describes the collaborative process of developing the end-of-training American
      Geriatrics Society (AGS) and Association of Directors of Geriatric Academic
      Programs (ADGAP) EPAs for Geriatric Medicine (AGS/ADGAP EPAs). The geriatrics
      EPAs describes a geriatrician's fundamental expertise and how geriatricians
      differ from general internists and family practitioners who care for older
      adults. 

PMID- 24749845
TI  - Chondrogenic differentiation of mesenchymal stem cells: challenges and
      unfulfilled expectations.
AB  - Articular cartilage repair and regeneration provides a substantial challenge in
      Regenerative Medicine because of the high degree of morphological and mechanical
      complexity intrinsic to hyaline cartilage due, in part, to its extracellular
      matrix. Cartilage remains one of the most difficult tissues to heal; even state
      of-the-art regenerative medicine technology cannot yet provide authentic
      cartilage resurfacing. Mesenchymal stem cells (MSCs) were once believed to be the
      panacea for cartilage repair and regeneration, but despite years of research,
      they have not fulfilled these expectations. It has been observed that MSCs have
      an intrinsic differentiation program reminiscent of endochondral bone formation,
      which they follow after exposure to specific reagents as a part of current
      differentiation protocols. Efforts have been made to avoid the resulting
      hypertrophic fate of MSCs; however, so far, none of these has recreated a fully
      functional articular hyaline cartilage without chondrocytes exhibiting a
      hypertrophic phenotype. We reviewed the current literature in an attempt to
      understand why MSCs have failed to regenerate articular cartilage. The challenges
      that must be overcome before MSC-based tissue engineering can become a front-line
      technology for successful articular cartilage regeneration are highlighted. 

PMID- 24749847
TI  - Repeat treatment of acute hereditary angioedema attacks with open-label icatibant
      in the FAST-1 trial.
AB  - Hereditary angioedema (HAE) is characterized by potentially life-threatening
      recurrent episodes of oedema. The open-label extension (OLE) phase of the For
      Angioedema Subcutaneous Treatment (FAST)-1 trial (NCT00097695) evaluated the
      efficacy and safety of repeated icatibant exposure in adults with multiple HAE
      attacks. Following completion of the randomized, controlled phase, patients could
      receive open-label icatibant (30 mg subcutaneously) for subsequent attacks. The
      primary end-point was time to onset of primary symptom relief, as assessed by
      visual analogue scale (VAS). Descriptive statistics were reported for
      cutaneous/abdominal attacks 1-10 treated in the OLE phase and individual
      laryngeal attacks. Post-hoc analyses were conducted in patients with >= 5 attacks
      across the controlled and OLE phases. Safety was evaluated throughout. During the
      OLE phase, 72 patients received icatibant for 340 attacks. For
      cutaneous/abdominal attacks 1-10, the median time to onset of primary symptom
      relief was 1.0-2.0 h. For laryngeal attacks 1-12, patient-assessed median time to
      initial symptom improvement was 0.3-1.2 h. Post-hoc analyses showed the time to
      onset of symptom relief based on composite VAS was consistent across repeated
      treatments with icatibant. One injection of icatibant was sufficient to treat
      88.2% of attacks; rescue medication was required in 5.3% of attacks. No icatibant
      related serious adverse events were reported. Icatibant provided consistent
      efficacy and was well tolerated for repeated treatment of HAE attacks. 

PMID- 24749848
TI  - Physiological control of dual rotary pumps as a biventricular assist device using
      a master/slave approach.
AB  - Dual rotary left ventricular assist devices (LVADs) can provide biventricular
      mechanical support during heart failure. Coordination of left and right pump
      speeds is critical not only to avoid ventricular suction and to match cardiac
      output with demand, but also to ensure balanced systemic and pulmonary
      circulatory volumes. Physiological control systems for dual LVADs must meet these
      objectives across a variety of clinical scenarios by automatically adjusting left
      and right pump speeds to avoid catastrophic physiological consequences. In this
      study we evaluate a novel master/slave physiological control system for dual
      LVADs. The master controller is a Starling-like controller, which sets flow rate
      as a function of end-diastolic ventricular pressure (EDP). The slave controller
      then maintains a linear relationship between right and left EDPs. Both left/right
      and right/left master/slave combinations were evaluated by subjecting them to
      four clinical scenarios (rest, postural change, Valsalva maneuver, and exercise)
      simulated in a mock circulation loop. The controller's performance was compared
      to constant-rotational-speed control and two other dual LVAD control systems:
      dual constant inlet pressure and dual Frank-Starling control. The results showed
      that the master/slave physiological control system produced fewer suction events
      than constant-speed control (6 vs. 62 over a 7-min period). Left/right
      master/slave control had lower risk of pulmonary congestion than the other
      control systems, as indicated by lower maximum EDPs (15.1 vs. 25.2-28.4 mm Hg).
      During exercise, master/slave control increased total flow from 5.2 to 10.1
      L/min, primarily due to an increase of left and right pump speed. Use of the left
      pump as the master resulted in fewer suction events and lower EDPs than when the
      right pump was master. Based on these results, master/slave control using the
      left pump as the master automatically adjusts pump speed to avoid suction and
      increases pump flow during exercise without causing pulmonary venous congestion. 

PMID- 24749849
TI  - African American women's preventative care usage: the role of social support and
      racial experiences and attitudes.
AB  - Research suggests that African Americans are less likely to utilise preventative
      care services than Americans of European descent, and that these patterns may
      contribute to racial health disparities in the United States. Despite the
      persistence of inequalities in preventative care utilisation, culturally relevant
      factors influencing the use of these gateway health services have been
      understudied among marginalised groups. Using a stratified sample of 205 low
      income African American women, this research examines the predictors of receiving
      a physical exam, with a particular emphasis on how differing levels of social
      support from friend and family networks and experiences of racial discrimination
      and cultural mistrust shape utilisation. The findings underscore the importance
      of traditional predictors of utilisation, including insurance status and having a
      usual physician. However, they also indicate that supportive ties to friendship
      networks are associated with higher predicted rates of having an annual physical
      exam, while social support from family and sentiments of cultural mistrust are
      associated with lower rates of utilisation. Broadly, the findings indicate that
      even as traditional predictors of help-seeking become less relevant, it will be
      critical to explore how variations in discrimination experiences and social
      relationships across marginalised groups drive patterns of preventative care
      utilisation. 

PMID- 24749850
TI  - Agreement of retinal nerve fiber layer defect location between red-free fundus
      photography and cirrus HD-OCT maps.
AB  - PURPOSE: To investigate the agreement of angular locations of retinal nerve fiber
      layer (RNFL) defect margins in glaucomatous eyes by using red-free fundus
      photographs and Cirrus high-definition optical coherence tomography (OCT) RNFL
      deviation and thickness maps. METHODS: We examined 380 RNFL defects that showed
      clear margins in red-free fundus photographs. The OCT deviation and thickness
      maps were overlaid on the corresponding red-free fundus photographs. A reference
      line was drawn between the disc center and the macular center. Lines were also
      drawn between the optic disc center and the point where the RNFL defect margins
      crossed the OCT scan circle. The angle between the reference and defect-margin
      lines defined the angular location of the defect margin. Angular locations of
      proximal (nearest to the reference) and distal (farthest from the reference) RNFL
      defect margins on OCT deviation and thickness maps were compared to the locations
      on red-free fundus photographs. RESULTS: The angular locations of proximal and
      distal RNFL defect margins on OCT thickness maps showed good agreement with red
      free fundus photographs. However, OCT deviation maps showed greater angular
      locations for both proximal and distal RNFL defect margins compared with red-free
      fundus photographs, especially in eyes with higher myopia (p < 0.05).
      CONCLUSIONS: Red-free fundus photographs and OCT thickness maps showed good
      agreement for the RNFL defect margin identification. However, this was not the
      case for deviation maps, especially in myopic eyes. This finding should be
      considered when evaluating RNFL defects using OCT maps.

PMID- 24749851
TI  - Nonlinear photonic diode behavior in energy-graded core-shell quantum well
      semiconductor rod.
AB  - Future technologies require faster data transfer and processing with lower loss.
      A photonic diode could be an attractive alternative to the present Si-based
      electronic diode for rapid optical signal processing and communication. Here, we
      report highly asymmetric photonic diode behavior with low scattering loss, from
      tapered core-shell quantum well semiconductor rods that were fabricated to have a
      large gradient in their bandgap energy along their growth direction. Local laser
      illumination of the core-shell quantum well rods yielded a huge contrast in light
      output intensities from opposite ends of the rod. 

PMID- 24749852
TI  - Multihydroxy dendritic upconversion nanoparticles with enhanced water
      dispersibility and surface functionality for bioimaging.
AB  - Upconversion nanoparticle (UCNP) as a new class of imaging agent is gaining
      prominence because of its unique optical properties. An ideal UCNP for bioimaging
      should simultaneously possess fine water dispersibility and favorable functional
      groups. In this paper, we present a simple but effective method to the synthesis
      of a UCNP-based nanohybrid bearing a multihydroxy hyperbranched polyglycerol
      (HPG) shell by the combination of a "grafting from" strategy with a ring-opening
      polymerization technique. The structure and morphology of the resulting UCNP-g
      HPG nanohybrid were characterized in detail by Fourier transform infrared, (1)H
      NMR, thermogravimetric analysis, and transmission electron microscopy
      measurements. The results reveal that the amount of grafted HPG associated with
      the thickness of the HPG shell can be well tuned. UCNP-g-HPG shows high water
      dispersibility and strong and stable upconversion luminescence. On the basis of
      its numerous surface hydroxyl groups, UCNP-g-HPG can be tailored by a
      representative fluorescent dye rhodamine B to afford a UCNP-g-HPG-RB nanohybrid
      that simultaneously presents upconversion and downconversion luminescence.
      Preliminary biological studies demonstrate that UCNP-g-HPG shows low
      cytotoxicity, high luminescent contrast, and deep light penetration depth, posing
      promising potential for bioimaging applications. 

PMID- 24749853
TI  - Epigenome-wide DNA methylation assay reveals placental epigenetic markers for
      noninvasive fetal single-nucleotide polymorphism genotyping in maternal plasma.
AB  - BACKGROUND: The use of DNA methylation difference between maternal blood cell and
      fetal (placental) DNA is one of the main areas of interest for the development of
      fetal epigenetics markers in maternal plasma. STUDY DESIGN AND METHODS: We
      employed a methylation array (HumanMethylation450 array, Illumina, Inc.) to
      identify novel biomarkers that are specially hypermethylated in placental DNA
      versus maternal blood cells in a genome-wide basis. Validation by bisulfite
      genomic sequencing was performed and the priority was given to potential targets
      that harbor differential methylated CpG sites overlapped with at least two
      methylation-sensitive restriction enzyme (MSRE) recognizing sites, as well as one
      polymorphic single-nucleotide polymorphism (SNP), within a short DNA stretch.
      Three candidate regions of PSMB8, SKI, and CHST11 gene were selected for
      developing a preliminary polymerase chain reaction assay with MSRE digestion of
      maternal plasma DNA. SNP genotypes were confirmed by direct sequencing. RESULTS:
      We identified 2944 and 5218 fetal-specific hypermethylated CpG sites in the first
      and third-trimester placenta, respectively, of which 2613 were overlapped,
      suggesting a consistency of differential methylation during the whole pregnancy.
      The array results were confirmed by bisulfite genomic sequencing. The preliminary
      tests in maternal plasma showed that postdigestion hypermathylated versions of
      these candidate molecules were detectable only in pregnant women. We further
      revealed that methylated targets in maternal plasma possessed the fetal SNP
      genotypes. CONCLUSION: The present studies systematically identified
      hypermethylated sites in fetal tissues and preliminarily demonstrated that some
      of the fetal epigenetic markers that contain informative SNPs have great
      potential for noninvasive fetal genetic diagnosis.

PMID- 24749854
TI  - Human identification by oral prosthesis analysis with probability rates higher
      than DNA analysis.
AB  - Several techniques are used to perform an appropriate and reliable human
      identification. Forensic dentistry has achieved great relevance over the past
      years. The aim of this article is to report the method used for the
      identification of a male body found in the colliquative stage of putrefaction.
      The identification of the victim was succeeded confronting the dental findings
      found in the corpse with the data present on dental records provided by his
      dentist. The major elements for the identity's recognition were a metal core and
      a prosthetic crown that were being fabricated. These elements associated with the
      dental records were compelling for the elucidation of the case, and a positive
      body identification was achieved with high levels of probability. In the present
      case, cadaveric analysis of stomatognathic system structures achieved a
      probability value higher than DNA identification techniques, emphasizing the
      importance of forensic dentistry. 

PMID- 24749855
TI  - Letter to the Editor--Methylenedioxypyrovalerone as a cause of excited delirium.

PMID- 24749856
TI  - Letter to the Editor--Setting professional standards for forensic anthropology in
      the United Kingdom.

PMID- 24749857
TI  - Commentary on: Crowder C, Rainwater CW, Fridie JS. Microscopic analysis of sharp
      force trauma in bone and cartilage: a validation study. J Forensic Sci
      2013;58(5):1119-26.

PMID- 24749858
TI  - Authors' response.

PMID- 24749859
TI  - Gilman D. Veith (1944-2013)--a dedication.

PMID- 24749860
TI  - Relationships between meaning in life, social and achievement events, and
      positive and negative affect in daily life.
AB  - Research on meaning in life has generally focused on global meaning judgments.
      This study examined how people's daily experiences, represented by events that
      occur in daily life, influence their perceived sense of meaning on a daily basis.
      One hundred sixty-two college students completed daily reports for 2 weeks. We
      examined the relationships among daily social and achievement events, daily
      positive and negative affect, and daily meaning in life. In addition, we tested
      the possible moderating influence of depressive symptoms on these relationships.
      Positive daily social and achievement events were related to greater daily
      meaning, above and beyond the contributions of daily positive and negative
      affect. Negative social and achievement events were related to less daily
      meaning, and negative achievement events covaried with daily meaning above and
      beyond positive and negative affect. Depression moderated the relationships
      between positive events and meaning, such that people who reported more
      depressive symptoms had greater increases in daily meaning in response to
      positive social and achievement events than individuals who reported fewer
      symptoms. These findings suggest the important role that daily events may play in
      fluctuations in people's affective experiences and sense of meaning in life. 

PMID- 24749861
TI  - Synthesis of novel tricyclic chromenone-based inhibitors of IRE-1 RNase activity.
AB  - Inositol-requiring enzyme 1 (IRE-1) is a kinase/RNase ER stress sensor that is
      activated in response to excessive accumulation of unfolded proteins, hypoxic
      conditions, calcium imbalance, and other stress stimuli. Activation of IRE-1
      RNase function exerts a cytoprotective effect and has been implicated in the
      progression of cancer via increased expression of the transcription factor XBP
      1s. Here, we describe the synthesis and biological evaluation of novel chromenone
      based covalent inhibitors of IRE-1. Preparation of a family of 8
      formyltetrahydrochromeno[3,4-c]pyridines was achieved via a Duff formylation that
      is attended by an unusual cyclization reaction. Biological evaluation in vitro
      and in whole cells led to the identification of 30 as a potent inhibitor of IRE-1
      RNase activity and XBP-1s expression in wild type B cells and human mantle cell
      lymphoma cell lines. 

PMID- 24749863
TI  - Genetic, morphological, and acoustic evidence reveals lack of diversification in
      the colonization process in an island bird.
AB  - Songbirds with recently (i.e., early Holocene) founded populations are suitable
      models for studying incipient differentiation in oceanic islands. On such systems
      each colonization event represents a different evolutionary episode that can be
      studied by addressing sets of diverging phenotypic and genetic traits. We
      investigate the process of early differentiation in the spectacled warbler
      (Sylvia conspicillata) in 14 populations separated by sea barriers from three
      Atlantic archipelagos and from continental regions spanning from tropical to
      temperate latitudes. Our approach involved the study of sexual acoustic signals,
      morphology, and genetic data. Mitochondrial DNA did not provide clear population
      structure. However, microsatellites analyses consistently identified two genetic
      groups, albeit without correspondence to subspecies classification and little
      correspondence to geography. Coalescent analyses showed significant evidence for
      gene flow between the two genetic groups. Discriminant analyses could not
      correctly assign morphological or acoustic traits to source populations.
      Therefore, although theory predicting that in isolated populations genetic,
      morphological, or acoustic traits can lead to radiation, we have strikingly
      failed to document differentiation on these attributes in a resident passerine
      throughout three oceanic archipelagos. 

PMID- 24749864
TI  - Redesigning photo-ID to improve unfamiliar face matching performance.
AB  - Viewers find it difficult to match photos of unfamiliar faces for identity.
      Despite this, the use of photographic ID is widespread. In this study we ask
      whether it is possible to improve face matching performance by replacing single
      photographs on ID documents with multiple photos or an average image of the
      bearer. In 3 experiments we compare photo-to-photo matching with photo-to-average
      matching (where the average is formed from multiple photos of the same person)
      and photo-to-array matching (where the array comprises separate photos of the
      same person). We consistently find an accuracy advantage for average images and
      photo arrays over single photos, and show that this improvement is driven by
      performance in match trials. In the final experiment, we find a benefit of 4
      image arrays relative to average images for unfamiliar faces, but not for
      familiar faces. We propose that conventional photo-ID format can be improved, and
      discuss this finding in the context of face recognition more generally.

PMID- 24749865
TI  - Water intensity assessment of shale gas resources in the Wattenberg field in
      northeastern Colorado.
AB  - Efficient use of water, particularly in the western U.S., is an increasingly
      important aspect of many activities including agriculture, urban, and industry.
      As the population increases and agriculture and energy needs continue to rise,
      the pressure on water and other natural resources is expected to intensify.
      Recent advances in technology have stimulated growth in oil and gas development,
      as well as increasing the industry's need for water resources. This study
      provides an analysis of how efficiently water resources are used for
      unconventional shale development in Northeastern Colorado. The study is focused
      on the Wattenberg Field in the Denver-Julesberg Basin. The 2000 square mile field
      located in a semiarid climate with competing agriculture, municipal, and
      industrial water demands was one of the first fields where widespread use of
      hydraulic fracturing was implemented. The consumptive water intensity is measured
      using a ratio of the net water consumption and the net energy recovery and is
      used to measure how efficiently water is used for energy extraction. The water
      and energy use as well as energy recovery data were collected from 200 Noble
      Energy Inc. wells to estimate the consumptive water intensity. The consumptive
      water intensity of unconventional shale in the Wattenberg is compared with the
      consumptive water intensity for extraction of other fuels for other energy
      sources including coal, natural gas, oil, nuclear, and renewables. 1.4 to 7.5
      million gallons is required to drill and hydraulically fracture horizontal wells
      before energy is extracted in the Wattenberg Field. However, when the large short
      term total freshwater-water use is normalized to the amount of energy produced
      over the lifespan of a well, the consumptive water intensity is estimated to be
      between 1.8 and 2.7 gal/MMBtu and is similar to surface coal mining. 

PMID- 24749866
TI  - Providing lifestyle behaviour change support for patients with psoriasis: an
      assessment of the existing training competencies across medical and nursing
      health professionals.
AB  - BACKGROUND: Psoriasis is associated with unhealthy lifestyle behaviours which
      contribute to psoriasis onset and severity. Health professionals who manage
      patients with psoriasis are well placed to support lifestyle change but few feel
      confident to do so. Little is known about the extent to which health promotion
      and lifestyle behaviour change (LBC) skills are included within post
      qualification training curricula. OBJECTIVES: This study aimed to systematically
      examine the content of post-qualification U.K. training curricula for health
      professionals across General Practice and Dermatology for evidence of behaviour
      change skills relating to the promotion of healthy lifestyles. METHODS: Core
      curricula documents from professional organizations were analysed for content to
      examine the extent to which curricula: (1) mentioned health promotion and LBC as
      part of the professional role; and/or (2) included health promotion and LBC as
      explicit training competencies or requirements for qualification. RESULTS: Of the
      11 core curricula documents analysed, we found 67 occurrences of terms related to
      LBC and health promotion. Most were in the General Practitioner curriculum (n =
      42; 62.7%), followed by the Dermatology Specialist Nurse curriculum (n = 14;
      20.9%) and Dermatologist curriculum (n = 11; 16.4%). No occurrences were found in
      the General Practitioner with a Special Interest in Dermatology curriculum. LBC
      knowledge, skills and attitudes were not clearly specified and only basic level
      LBC competencies were included. CONCLUSIONS: Development of post-qualification
      curricula would ensure health professionals are equipped with the necessary
      knowledge, skills and attitudes to support LBC for patients with psoriasis. This
      is of particular relevance, given the evidence linking unhealthy lifestyles with
      psoriasis outcomes.

PMID- 24749868
TI  - Iron-catalyzed radical oxidative coupling reaction of aryl olefins with 1,3
      dithiane.
AB  - An alternative method to an iron-catalyzed radical oxidative cross-coupling
      reaction followed by 2-chloro-1,3-dithiane and aryl olefins for the synthesis of
      beta-chloro substituent 1,3-dithiane products is presented. The described method
      has the advantage of mildness of the reaction conditions and tolerates a variety
      of functional groups. Preliminary mechanistic studies have confirmed the first
      example of a coupling of 1,3-dithiane with unactivated alkenes that proceeds via
      an iron-catalyzed oxidative radical intermediate along the reaction pathway. 

PMID- 24749867
TI  - SB-RA-2001 inhibits bacterial proliferation by targeting FtsZ assembly.
AB  - FtsZ has been recognized as a promising antimicrobial drug target because of its
      vital role in bacterial cell division. In this work, we found that a taxane SB-RA
      2001 inhibited the proliferation of Bacillus subtilis 168 and Mycobacterium
      smegmatis cells with minimal inhibitory concentrations of 38 and 60 MUM,
      respectively. Cell lengths of these microorganisms increased remarkably in the
      presence of SB-RA-2001, indicating that it inhibits bacterial cytokinesis. SB-RA
      2001 perturbed the formation of the FtsZ ring in B. subtilis 168 cells and also
      affected the localization of the late cell division protein, DivIVA, at the
      midcell position. Flow cytometric analysis of the SB-RA-2001-treated cells
      indicated that the compound did not affect the duplication of DNA in B. subtilis
      168 cells. Further, SB-RA-2001 treatment did not affect the localization of the
      chromosomal partitioning protein, Spo0J, along the two ends of the nucleoids and
      also had no discernible effect on the nucleoid segregation in B. subtilis 168
      cells. The agent also did not appear to perturb the membrane potential of B.
      subtilis 168 cells. In vitro, SB-RA-2001 bound to FtsZ with modest affinity,
      promoted the assembly and bundling of FtsZ protofilaments, and reduced the GTPase
      activity of FtsZ. GTP did not inhibit the binding of SB-RA-2001 to FtsZ,
      suggesting that it does not bind to the GTP binding site on FtsZ. A computational
      analysis indicated that SB-RA-2001 binds to FtsZ in the cleft region between the
      C-terminal domain and helix H7, and the binding site of SB-RA-2001 on FtsZ
      resembled that of PC190723, a well-characterized inhibitor of FtsZ. The findings
      collectively suggested that SB-RA-2001 inhibits bacterial proliferation by
      targeting the assembly dynamics of FtsZ, and this can be exploited further to
      develop potent FtsZ-targeted antimicrobials. 

PMID- 24749869
TI  - Development of high-temperature strain instrumentation for in situ SEM evaluation
      of ductility dip cracking.
AB  - Nowadays, the implementation of sophisticated in situ electron microscopy tests
      is providing new insights in several areas. In this work, an in situ high
      temperature strain test into a scanning electron microscope was developed. This
      setup was used to study the grain boundary sliding mechanism and its effect on
      the ductility dip cracking. This methodology was applied to study the mechanical
      behaviour of Ni-base filler metal alloys ERNiCrFe-7 and ERNiCr-3, which were
      evaluated between 700 degrees C and 1000 degrees C. The ductility dip cracking
      susceptibility (threshold strain; epsilonmin) for both alloys was quantified. The
      epsilonmin of ERNiCrFe-7 and ERNiCr-3 alloys were 7.5% and 16.5%, respectively,
      confirming a better resistance of ERNiCr-3 to ductility dip cracking.
      Furthermore, two separate components of grain boundary sliding, pure sliding (Sp)
      and deformation sliding (Sd), were identified and quantified. A direct and
      quantitative link between grain boundary tortuosity, grain boundary sliding and
      ductility dip cracking resistance has been established for the ERNiCrFe-7 and
      ERNiCr-3 alloys.

PMID- 24749870
TI  - Biological evaluation of liposome-encapsulated hemoglobin surface-modified with a
      novel PEGylated nonphospholipid amphiphile.
AB  - Traumatic injury is often associated with hemorrhagic shock. Liposome
      encapsulated hemoglobin (LEH) is being developed as an artificial oxygen carrier
      to address post-hemorrhage oxygen and volume deficit. Here, we report a new
      composition of LEH based on the use of polyethylene glycol (PEG2K ) conjugated
      with nonphospholipid hexadecylcarbamoylmethylhexadecanoate (HDAS) to modify the
      surface of LEH particles. LEH was manufactured by the high-pressure
      homogenization method using dipalmitoylphosphatidylcholine (~38 mol%),
      cholesterol (~38 mol%), HDAS (~20 mol%), and highly purified stroma-free human
      hemoglobin. HDAS-PEG2K was postinserted into the resultant LEH to generate HDAS
      PEG2K -LEH. We investigated the potential immune response to HDAS-PEG2K -LEH in a
      mice model. At the same time, the preparation was tested in a rat model to study
      the effect of repeated HDAS-PEG2K -LEH injection over 4 weeks. We found that HDAS
      PEG2K modification substantially reduced the circulating levels of anaphylatoxins
      C3a and C5a, as well as plasma levels of thromboxane B2, in mice. Repeated
      injections of HDAS-PEG2K -LEH in rats did not appear to alter its clearance
      profile after 4 weeks of treatment. No antibody response against human hemoglobin
      or PEG was detected in rat plasma. Histological observations of lung, liver,
      spleen, and kidney were not significantly different between saline-treated rats
      and HDAS-PEG2K -LEH-treated rats. Immunohistochemical staining for rat heme
      oxygenase-1 (HO-1) did not show induced expression of HO-1 in these organs. These
      results suggest that the new surface modification of LEH is immune-neutral and
      does not adversely affect histology even after repeated administration. 

PMID- 24749871
TI  - Mapping the fine specificity of ABO monoclonal reagents with A and B type
      specific function-spacer-lipid constructs in kodecytes and inkjet printed on
      paper.
AB  - BACKGROUND: Monoclonal (MoAb) reagents are routinely used and are usually very
      reliable for the serologic determination of ABO blood types. However, the fine
      specificity and cross-reactivity of these reagents are often unknown,
      particularly against synthetic antigens used in some diagnostic assays. If
      nonserologic assays or very sensitive techniques other than those specifically
      prescribed by the manufacturer are used, then there is a risk of incorrect
      interpretation of results. STUDY DESIGN AND METHODS: Forty-seven MoAbs and two
      polyclonal ABO reagents were tested against red blood cell (RBC) kodecytes
      prepared with A trisaccharide, A Type 1, A Type 2, A Type 3, A Type 4, B
      trisaccharide, B Type 1, B Type 2, acquired B trisaccharide, and Le(a)
      trisaccharide function-spacer-lipid (FSL) constructs. Natural RBCs were tested in
      parallel. In addition these FSL constructs were printed onto paper with a desktop
      inkjet printer and used in a novel immunoassay that identifies reactivity through
      the appearance of alphanumeric characters. RESULTS: Mapping of MoAbs with
      kodecytes and printed FSL constructs revealed a series of broad recognition
      patterns. All ABO MoAbs tested were reactive with the RBC dominant Type 2 ABO
      antigens. Unexpectedly some anti-A reagents were reactive against the B Type 1
      antigen, while others were poorly reactive with trisaccharide antigens.
      CONCLUSIONS: All ABO MoAbs detect the RBC dominant Type 2 ABO antigens; however,
      some reagents may show minor reactivity with inappropriate blood group antigens,
      which needs to be considered when using these reagents in alternative or highly
      sensitive analytic systems.

PMID- 24749872
TI  - Creeping edgework: carnivalesque consumption and the social experience of health
      risk.
AB  - This article contributes to an understanding of voluntary health risk based on
      the regular, excessive intake of food and alcohol in the micro-cultural setting.
      By drawing on and extending edgework theory our aim is to conceptualise the
      riskiness of carnivalesque consumption as a medium for expression and performance
      in two separate community contexts. Using ethnographic research methods, we
      explore the consumption of calorie-dense, low nutrient food for gamers and the
      use of alcohol for hipsters. Our findings are reported over four key themes. The
      first and last consider how carnivalesque consumption provides sensations for
      multi-sensory loss of self and a shared emancipation from day-to-day moderation.
      The second and third explore how community members prepare and exercise control
      over their consumption to manage risks related to an 'immediate edge'. We discuss
      how carnivalesque behaviour, when ritualised, establishes a trajectory that
      creeps towards a more 'distant edge' characterised by longer term health
      consequences. We argue that the transcendental experiences that are part and
      parcel of edgework can be enacted by products that are traditionally
      conceptualised as mundane and that the risks of consuming them are largely
      accumulative rather than instantaneous. Implications for health interventions are
      included. 

PMID- 24749873
TI  - Moving toward biospecimen harmonization with evidence-based practices.

PMID- 24749874
TI  - Fit for purpose frozen tissue collections by RNA integrity number-based quality
      control assurance at the Erasmus MC tissue bank.
AB  - About 5000 frozen tissue samples are collected each year by the Erasmus Medical
      Center tissue bank. Two percent of these samples are randomly selected annually
      for RNA isolation and RNA Integrity Number (RIN) measurement. A similar quality
      assessment was conducted during centralization of a 20-year-old tissue collection
      from the cancer institute, a 15-year-old liver sample archive (-80 degrees C),
      and a 13-year-old clinical pathology frozen biopsy archive (Liquid Nitrogen).
      Samples were divided into either high-quality (RIN >=6.5) or low-quality overall
      categories, or into four "fit-for-purpose" quality groups: RIN <5: not reliable
      for demanding downstream analysis; 5 <=RIN <6: suitable for RT-qPCR; 6 <=RIN <8:
      suitable for gene array analysis; and RIN >=8: suitable for all downstream
      techniques. In general, low RIN values were correlated with fatty, fibrous,
      pancreatic, or necrotic tissue. When the percentage of samples with RIN >=6.5 is
      higher than 90%, the tissue bank performance is adequate. The annual 2011 quality
      control assessment showed that 90.3% (n=93) of all samples had acceptable RIN
      values; 97.4% (n=39) of the cancer institute collection had RIN values above 6.5;
      and 88.6% (n=123) of samples from the liver sample archive collection had RIN
      values higher than 6.5. As the clinical pathology biopsy collection contained
      only 58.8% (n=24) acceptable samples, the procurement protocols used for these
      samples needed immediate evaluation. When the distribution of RIN values of the
      different collections were compared, no significant differences were found,
      despite differences in average storage time and temperature. According to the
      principle of "fit-for-purpose" distribution, the vast majority of samples are
      considered good enough for most downstream techniques. In conclusion, an annual
      tissue bank quality control procedure provides useful information on tissue
      sample quality and sheds light on where and if improvements need to be made. 

PMID- 24749875
TI  - Introducing research initiatives into healthcare: what do doctors think?
AB  - BACKGROUND: Current national and international policies emphasize the need to
      develop research initiatives within our health care system. Institutional
      biobanking represents a modern, large-scale research initiative that is reliant
      upon the support of several aspects of the health care organization. This
      research project aims to explore doctors' views on the concept of institutional
      biobanking and to gain insight into the factors which impact the development of
      research initiatives within healthcare systems. METHODS: Qualitative research
      study using semi-structured interviews. The research was conducted across two
      public teaching hospitals in Sydney, Australia where institutional biobanking was
      being introduced. Twenty-five participants were interviewed, of whom 21 were
      medical practitioners at the specialist trainee level or above in a specialty
      directly related to biobanking; four were key stakeholders responsible for the
      design and implementation of the biobanking initiative. RESULTS: All participants
      strongly supported the concept of institutional biobanking. Participants
      highlighted the discordance between the doctors who work to establish the biobank
      (the contributors) and the researchers who use it (the consumers). Participants
      identified several barriers that limit the success of research initiatives in the
      hospital setting including: the 'resistance to change' culture; the difficulties
      in engaging health professionals in research initiatives; and the lack of
      incentives offered to doctors for their contribution. Doctors positively valued
      the opportunity to advise the implementation team, and felt that the initiative
      could benefit from their knowledge and expertise. CONCLUSION: Successful
      integration of research initiatives into hospitals requires early collaboration
      between the implementing team and the health care professionals to produce a plan
      that is sensitive to the needs of the health professionals and tailored to the
      hospital setting. Research initiatives must consider incentives that encourage
      doctors to adopt operational responsibility for hospital research initiatives.

PMID- 24749877
TI  - Cancer patient perceptions about biobanking and preferred timing of consent.
AB  - Little is known about how cancer patients feel about donating their tissue,
      especially in a multiethnic population. Structured interviews were conducted with
      30 patients recently diagnosed with cancer, referred to the study by six cancer
      surgeons and oncologists and by other patients in the study. The participants
      reported a variety of cancers, and the sample reflected the racial distribution
      of Hawai'i, including Caucasians (23%), Native Hawaiians and Pacific Islanders
      (27%), Asians (37%), Hispanics (7%), Native Americans (3%), and African Americans
      (3%). The interview questions and analysis were guided by the Framework Approach,
      with interview questions based on pre-set aims. Findings suggest that most cancer
      patients would donate cancer tissue to science, especially if informed that doing
      so could help researchers find causes of and cures for cancer. Patients varied on
      when in their cancer journey they would be most receptive to being asked for a
      donation, however two-thirds thought they would be more receptive if approached
      after surgery. Only three of the 30 patients said they would want to be re
      consented each time their tissue is requested for research. They identified their
      physician as the preferred messenger regarding tissue donation. No obvious
      differences were seen by race. Findings confirm those of other researchers who
      have reported broad support for biobank participation if informed consent and
      confidentiality could be assured. Given that the physician was seen as the key
      messenger about biobanking, more education is needed around cancer tissue
      collection for physicians, as well as for cancer patients. 

PMID- 24749876
TI  - Evaluation of sericin as a fetal bovine serum-replacing cryoprotectant during
      freezing of human mesenchymal stromal cells and human osteoblast-like cells.
AB  - A reliable, cryoprotective, xeno-free medium suitable for different cell types is
      highly desirable in regenerative medicine. There is danger of infection or
      allergic reaction with the use of fetal bovine serum (FBS), making it problematic
      for medical applications. The aim of the present study was to develop an FBS-free
      cryoprotective medium for human mesenchymal stromal cells (hMSCs; primary cells)
      and immortalized human osteoblasts (SAOS-2 cell line). Furthermore, we endeavored
      to eliminate or reduce the presence of dimethyl sulfoxide (DMSO) in the medium.
      Sericin, a sticky protein derived from the silkworm cocoon, was investigated as a
      substitute for FBS and DMSO in the freezing medium. Cell viability (24 hours
      after thawing, both hMSC and SAOS-2) and colony-forming ability (2 weeks after
      thawing, only for hMSCs) were both determined. The FBS-free medium with 1%
      sericin in 10% DMSO was found to be a suitable freezing medium for primary hMSCs,
      in contrast to immortalized human osteoblasts. Surprisingly, the storage of hMSCs
      in a cultivation medium with only 10% DMSO also provided satisfactory results.
      Any drop in DMSO concentration led to significantly worse survival of cells, with
      little improvement in hMSC survival in the presence of sericin. Thus, sericin may
      substitute for FBS in the freezing medium for primary hMSCs, but cannot
      substitute for DMSO. 

PMID- 24749878
TI  - Clinical biospecimens: reference materials, certified for nominal properties?
AB  - This report makes the case for clinical biospecimens to be certified for nominal
      properties, in particular the diagnosis, and to attain the level of Reference
      Materials. Clinical certified biospecimens that are collected, processed,
      characterized, stored, and distributed by biobanks are urgently needed to
      facilitate diagnostic test development, evaluation, and quality assurance. Four
      examples are provided to illustrate this purpose and the certification approaches
      that could be applied are proposed. 

PMID- 24749879
TI  - Public perceptions of cohort studies and biobanks in Germany.
AB  - Cohort studies and biobank projects have led to public discussions in several
      European countries in the past. In Germany, many medium-sized studies are
      currently running successfully in terms of respondent rates. However, EU-wide
      research on general public perceptions of biobanks and cohort studies have shown
      that Germany is among those countries where people express the highest reluctance
      for providing body material and other data for research purposes. Because of
      early efforts of the just-initiated German National Cohort Study, we are able to
      begin to investigate in greater detail how various groups of people across
      Germany reflect and discuss the ongoing implementation of cohort studies and
      biobanking in Germany. Our research is based on 15 focus group discussions in
      four German regions, as well as on Eurobarometer poll data on biobanking. 

PMID- 24749880
TI  - Factors associated with willingness to participate in biospecimen research among
      Chinese Americans.
AB  - A paucity of information exists on the recruitment of Asian Americans for
      biospecimen research. Although studies show that Chinese Americans are at high
      risk for hepatitis B virus (HBV) infection, little is known about their
      willingness to participate in HBV-related biospecimen research and how knowledge,
      attitudes, and cultural factors impact their willingness to participate. The
      study was guided by Community-Based Participatory Research principles. Data were
      derived from an assessment study on HBV-related biospecimen research
      participation among Chinese Americans in the Philadelphia region. The assessment
      was conducted with 415 Chinese Americans recruited from eight Chinese community
      based organizations. Cultural beliefs, knowledge, and attitudes toward
      biospecimen research were examined for associations with their willingness to
      participate in biospecimen banking research. Overall, 192 (46.3%) of 415
      participants who completed the assessment indicated they were willing to
      participate if they were invited to donate blood to be frozen and stored for
      future HBV biospecimen studies. Cultural variables significant in bivariate
      analysis included collectivism, knowledge about biospecimen research, and Yin
      Yang beliefs. Fatalism and individualism were not associated with participation
      willingness. In multivariate analysis, age, health care attitudes, and trust were
      significantly associated with willingness to participate in biospecimen banking
      research. Asian American communities have little knowledge of biospecimen banking
      and will benefit from educational campaigns that emphasize collective benefits
      and attitudes towards and trust in the health care system. Understanding cultural
      factors is important for improving Chinese Americans' knowledge, awareness, and
      intentions of participation in biospecimen research. Similar efforts need to be
      undertaken to develop culturally appropriate educational intervention programs to
      increase participation in biospecimen research among other Asian American groups.

PMID- 24749881
TI  - Optimization of phytoplankton preservative concentrations to reduce damage during
      long-term storage.
AB  - A study was performed to establish the optimal concentration of traditional
      preservatives or fixatives such as formaldehyde and acidic Lugol's iodine, in
      order to preserve phytoplankton samples for long-term storage without the
      introduction of artifacts or other physical aberrations. The goal of the study
      was to avoid any visible morphological changes to the preserved cells, minimizing
      the errors induced by traditional preservative concentrations, and ensuring
      better accuracy of ecological analyses. We found that both formaldehyde and
      acidic Lugol's iodine have adverse effects on the preservation of samples.
      Trichodesmium erythraeum was found to be most susceptible to the effects of
      acidic Lugol's iodine, since it displayed the highest degree of chain
      fragmentation when this preservative was used. However, we found that 2.0% (v/v)
      formaldehyde, 2.5% (v/v) acidic Lugol's iodine, and 2.0% (v/v)
      formaldehyde+2.5%(v/v) acidic Lugol's iodine combined were most promising, with
      the latter the most effective even after 3 weeks of preservation. This study also
      revealed that, in general, the centric diatom species were more sensitive to long
      term preservation than their pennate counterparts. The present study is
      significant as it sheds light on the damage endured by phytoplankton cells during
      long-term preservation, which can lead to erroneous and biased results upon
      analyses. The optimal concentration of preservative established experimentally
      from a wide variety of concentrations caused comparatively moderate changes to
      the cell dimensions as well as effectively prevented microbial contamination. 

PMID- 24749882
TI  - National Cancer Institute Biospecimen Evidence-Based Practices: a novel approach
      to pre-analytical standardization.
AB  - Variable biospecimen collection, processing, and storage practices may introduce
      variability in biospecimen quality and analytical results. This risk can be
      minimized within a facility through the use of standardized procedures; however,
      analysis of biospecimens from different facilities may be confounded by
      differences in procedures and inferred biospecimen quality. Thus, a global
      approach to standardization of biospecimen handling procedures and their
      validation is needed. Here we present the first in a series of procedural
      guidelines that were developed and annotated with published findings in the field
      of human biospecimen science. The series of documents will be known as NCI
      Biospecimen Evidence-Based Practices, or BEBPs. Pertinent literature was
      identified via the National Cancer Institute (NCI) Biospecimen Research Database
      ( brd.nci.nih.gov ) and findings were organized by specific biospecimen pre
      analytical factors and analytes of interest (DNA, RNA, protein, morphology). Meta
      analysis results were presented as annotated summaries, which highlight
      concordant and discordant findings and the threshold and magnitude of effects
      when applicable. The detailed and adaptable format of the document is intended to
      support the development and execution of evidence-based standard operating
      procedures (SOPs) for human biospecimen collection, processing, and storage
      operations. 

PMID- 24749883
TI  - DNA fingerprinting: a quality control case study for human biospecimen
      authentication.
AB  - This case study illustrates the usefulness of the DNA fingerprinting method in
      biobank quality control (QC) procedures and emphasizes the need for detailed and
      accurate record keeping during processing of biological samples. It also
      underlines the value of independent third-party assessment to identify points at
      which errors are most likely to have occurred when unexpected results are
      obtained from biospecimens. 

PMID- 24749884
TI  - The Research Biobank of the Year Competition of the European, Middle Eastern and
      African Society for Biopreservation and Biobanking (ESBB): aims and achievements.
AB  - With the increasing number of research biobanks and the importance of their role
      in supporting medical and biological research, the development and sharing of
      biobanking best practices and benchmarking standards has become paramount. To
      promote outstanding biobank services for research, the Research Biobank of the
      Year Competition (RBYC) has been inaugurated by the European, Middle-Eastern, and
      African Society for Biopreservation and Biobanking (ESBB) in October 2013. The
      procedures for the call and evaluation procedure, including the newly developed
      scoring system, are presented here. The statistics and evaluation results of the
      first year's applications, as well as the experiences of the jury are reported
      here, and improvements for the RBYC in subsequent years are proposed. Beyond
      offering a unique benchmarking opportunity for biobanks, the RBYC is discussed as
      a novel tool to enhance biobank quality, transparency, usage, connectivity,
      innovation, and sustainability. 

PMID- 24749886
TI  - Postoperative morphine concentration in infants with or without biliary atresia
      and its association with hepatic blood flow.
AB  - We measured pre-operative hepatic blood flow and postoperative morphine
      concentration in infants with or without biliary atresia. Thirty-four infants (0
      3 months) with biliary atresia undergoing portoenterostomy (Kasai operation) were
      included and hepatic blood flow was assessed by magnetic resonance imaging before
      surgery in 12 of them. Sixteen subjects (0-3 months) without liver disease
      undergoing abdominal or pelvic surgery acted as controls and six of them had
      hepatic blood flow assessed. Intravenous morphine (8 MUg.kg(-1).h(-1)) was
      administered to all patients postoperatively. The median (IQR [range]) relative
      hepatic blood flow was 3.51 (2.72-3.88 [1.68-4.43]) with and 3.15 (2.66-4.42
      [2.30-5.01]) without biliary atresia (p = 0.851). The median (IQR [range])
      morphine concentration after 24 h infusion was 5.9 (4.5-16.4 [2.9-42.2]) ng.ml(
      1) and 6.4 (3.2-12.0 [1.9-48.6]) ng.ml(-1) , respectively (p = 0.460). An inverse
      regression relation was found between the morphine concentration and the hepatic
      perfusion index (R(2) = 0.519, p = 0.001). Compensatory increases in hepatic
      arterial blood flow maintain the total hepatic blood flow in infants with biliary
      atresia.

PMID- 24749887
TI  - Dutcher bodies: cytoplasmic inclusions within the nucleus.

PMID- 24749888
TI  - Inhibition of alpha-smooth muscle actin expression and migration of pterygium
      fibroblasts by coculture with amniotic mesenchymal stem cells.
AB  - PURPOSE: Epithelial-mesenchymal transition (EMT) of normal conjunctival tissues
      is a major reason of pterygium generation; alpha-smooth muscle actin (alpha-SMA)
      is a maker in EMT. In this study, we investigated if human amniotic mesenchymal
      stem cells (hAMSCs) can inhibit alpha-SMA expression and migration of human
      pterygium fibroblasts (hPFs) in vitro. MATERIALS AND METHODS: Coculture of hAMSCs
      and hPFs was completed by using a Transwell coculture system. The alpha-SMA
      expression of hPFs was detected by immunocytochemistry and western blot analysis.
      The migration ability of hPFs was measured by means of a migration assay.
      Immunoreactivity for alpha-SMA was detected in all pterygium fibroblasts
      examined. RESULTS: The expression of alpha-SMA in cocultured hPFs was
      significantly lower than in hPFs. Similar result was demonstrated in western blot
      analysis. In addition, migration assay showed that hAMSCs reduce the migration of
      hPFs. CONCLUSIONS: These results suggested that hAMSCs have the potential to
      inhibit the generation and invasiveness of pterygium in vitro.

PMID- 24749890
TI  - Examining the impact of child parent relationship therapy (CPRT) on family
      functioning.
AB  - Research supports that child parent relationship therapy (CPRT), a filial therapy
      approach, has strong effects on participating parents and children. Some
      speculate that filial therapy improves the family system; however, minimal
      research exists to support this claim. Using a single-case design, researchers
      examined CPRT's impact on the functioning of 8 families. Results revealed that 6
      families experienced statistically significant improvements in targeted areas of
      family functioning. Results from self-reported measures indicated that 7 families
      improved in family satisfaction, 4 in cohesion, 3 in communication, and 1 in
      flexibility. Observational measures also revealed improvements: 5 families in
      flexibility, 4 families in cohesion, and 4 families in communication. The results
      support that the benefits of CPRT may extend to the family system. 

PMID- 24749889
TI  - Platform technologies for decellularization, tunic-specific cell seeding, and in
      vitro conditioning of extended length, small diameter vascular grafts.
AB  - The aim of this study was to generate extended length, small diameter vascular
      scaffolds that could serve as potential grafts for treatment of acute ischemia.
      Biological tissues are considered excellent scaffolds, which exhibit adequate
      biological, mechanical, and handling properties; however, they tend to
      degenerate, dilate, and calcify after implantation. We hypothesized that
      chemically stabilized acellular arteries would be ideal scaffolds for development
      of vascular grafts for peripheral surgery applications. Based on promising
      historical data from our laboratory and others, we chose to decellularize bovine
      mammary and femoral arteries and test them as scaffolds for vascular grafting.
      Decellularization of such long structures required development of a novel
      "bioprocessing" system and a sequence of detergents and enzymes that generated
      completely acellular, galactose-(alpha1,3)-galactose (alpha-Gal) xenoantigen-free
      scaffolds with preserved collagen, elastin, and basement membrane components.
      Acellular arteries exhibited excellent mechanical properties, including burst
      pressure, suture holding strength, and elastic recoil. To reduce elastin
      degeneration, we treated the scaffolds with penta-galloyl glucose and then
      revitalized them in vitro using a tunic-specific cell approach. A novel
      atraumatic endothelialization protocol using an external stent was also developed
      for the long grafts and cell-seeded constructs were conditioned in a flow
      bioreactor. Both decellularization and revitalization are feasible but cell
      retention in vitro continues to pose challenges. These studies support further
      efforts toward clinical use of small diameter acellular arteries as vascular
      grafts. 

PMID- 24749891
TI  - Treatment of gastroesophageal reflux disease: two new oral formulations
      dexlansoprazole MR and esomezol (esomeprazole strontium).
AB  - INTRODUCTION: The prevalence of gastroesophageal reflux disease continues to
      increase with the aging population and the obesity epidemic. Therapeutic failures
      can have significant detrimental effects in patients. Recently, dexlansoprazole
      MR and esomeprazole strontium were introduced to the class of proton pump
      inhibitors (PPIs). AREAS COVERED: This article will review the pharmacodynamics
      and pharmacokinetics of dexlansoprazole MR and esomeprazole strontium. Using the
      keywords 'dexlansoprazole MR' and 'esomeprazole strontium' in the search engines
      of PubMed, Cochrane Reviews and Google, we were able to identify peer-reviewed
      publications, abstracts and presentations at national society educations meetings
      and present a balanced view of the available data. EXPERT OPINION:
      Dexlansoprazole MR and esomeprazole strontium offer an innovative delivery
      mechanism compared to conventional PPIs. Further trials are necessary in order to
      establish superiority.

PMID- 24749892
TI  - Synthetic marijuana "K2" induced ITP.
AB  - Immune thrombocytopenia (ITP) is a heterogeneous disease which can be primary or
      secondary due to other conditions such as drugs. CB2 receptors (CB2R) also have a
      role in the ITP pathogenesis as CB2 receptor gene (CNR2) polymorphisms are
      associated with chronic immune thrombocytopenia and autoimmune diseases. K2 is
      synthetic marijuana which acts on cannabinoid receptors that are found on immune
      cells and thrombocytes. Here, we present a case who presented with ITP secondary
      to K2 usage and was successfully treated with 1 mg/kg prednisolone. This is the
      first ITP case in the literature due to K2. It is important in the era of the new
      drugs development of the CB2R mimetics. 

PMID- 24749894
TI  - Redox-switchable copper(I) metallogel: a metal-organic material for selective and
      naked-eye sensing of picric acid.
AB  - Thiourea (TU), a commercially available laboratory chemical, has been discovered
      to introduce metallogelation when reacted with copper(II) chloride in aqueous
      medium. The chemistry involves the reduction of Cu(II) to Cu(I) with concomitant
      oxidation of thiourea to dithiobisformamidinium dichloride. The gel formation is
      triggered through metal-ligand complexation, i.e., Cu(I)-TU coordination and
      extensive hydrogen bonding interactions involving thiourea, the disulfide
      product, water, and chloride ions. Entangled network morphology of the gel
      selectively develops in water, maybe for its superior hydrogen-bonding ability,
      as accounted from Kamlet-Taft solvent parameters. Complete and systematic
      chemical analyses demonstrate the importance of both Cu(I) and chloride ions as
      the key ingredients in the metal-organic coordination gel framework. The gel is
      highly fluorescent. Again, exclusive presence of Cu(I) metal centers in the gel
      structure makes the gel redox-responsive and therefore it shows reversible gel
      sol phase transition. However, the reversibility does not cause any morphological
      change in the gel phase. The gel practically exhibits its multiresponsive nature
      and therefore the influences of different probable interfering parameters (pH,
      selective metal ions and anions, selective complexing agents, etc.) have been
      studied mechanistically and the results might be promising for different
      applications. Finally, the gel material shows a highly selective visual response
      to a commonly used nitroexplosive, picric acid among a set of 19 congeners and
      the preferred selectivity has been mechanistically interpreted with density
      functional theory-based calculations. 

PMID- 24749893
TI  - 3-Substituted-N-(4-hydroxynaphthalen-1-yl)arylsulfonamides as a novel class of
      selective Mcl-1 inhibitors: structure-based design, synthesis, SAR, and
      biological evaluation.
AB  - Mcl-1, an antiapoptotic member of the Bcl-2 family of proteins, is a validated
      and attractive target for cancer therapy. Overexpression of Mcl-1 in many cancers
      results in disease progression and resistance to current chemotherapeutics.
      Utilizing high-throughput screening, compound 1 was identified as a selective Mcl
      1 inhibitor and its binding to the BH3 binding groove of Mcl-1 was confirmed by
      several different, but complementary, biochemical and biophysical assays. Guided
      by structure-based drug design and supported by NMR experiments, comprehensive
      SAR studies were undertaken and a potent and selective inhibitor, compound 21,
      was designed which binds to Mcl-1 with a Ki of 180 nM. Biological
      characterization of 21 showed that it disrupts the interaction of endogenous Mcl
      1 and biotinylated Noxa-BH3 peptide, causes cell death through a Bak/Bax
      dependent mechanism, and selectively sensitizes EMU-myc lymphomas overexpressing
      Mcl-1, but not EMU-myc lymphoma cells overexpressing Bcl-2. Treatment of human
      leukemic cell lines with compound 21 resulted in cell death through activation of
      caspase-3 and induction of apoptosis. 

PMID- 24749896
TI  - A versatile, fast, and efficient method of visible-light-induced surface grafting
      polymerization.
AB  - To overcome the problem caused by the lability of the Au-S bond, we demonstrate
      the first use of Mn2(CO)10 for visible-light-induced surface grafting
      polymerization on Au surfaces in this paper. The visible-light-induced surface
      grafting of poly(N-isopropylacrylamide) (PNIPAAm) has the features of a
      "controlled" polymerization, which is characterized by a linear relationship
      between the thickness of the grafting layer and the monomer concentration.
      Ellipsometry indicated the formation of PNIPAAm films of up to ~200 nm in
      thickness after only 10 min of polymerization at room temperature, demonstrating
      that this is a very fast process in comparison with traditional grafting
      polymerization techniques. Moreover, to demonstrate the potential applications of
      our approach, different substrates grafted by PNIPAAm and the covalent
      immobilization of a range of polymers on Au surfaces were also demonstrated.
      Considering the advantages of simplicity, efficiency, and mild reaction
      conditions as well as the ability of catecholic derivatives to bind to a large
      variety of substrates, this visible-light-induced grafting method is expected to
      be useful in designing functional interfaces. 

PMID- 24749895
TI  - HIV-related sexual risk behavior among African American adolescent girls.
AB  - BACKGROUND: Latent class analysis (LCA) is a useful statistical tool that can be
      used to enhance understanding of how various patterns of combined sexual behavior
      risk factors may confer differential levels of HIV infection risk and to identify
      subtypes among African American adolescent girls. METHODS: Data for this analysis
      is derived from baseline assessments completed prior to randomization in an HIV
      prevention trial. Participants were African American girls (n=701) aged 14-20
      years presenting to sexual health clinics. Girls completed an audio computer
      assisted self-interview, which assessed a range of variables regarding sexual
      history and current and past sexual behavior. RESULTS: Two latent classes were
      identified with the probability statistics for the two groups in this model being
      0.89 and 0.88, respectively. In the final multivariate model, class 1 (the
      "higher risk" group; n=331) was distinguished by a higher likelihood of >5
      lifetime sexual partners, having sex while high on alcohol/drugs, less frequent
      condom use, and history of sexually transmitted diseases (STDs), when compared
      with class 2 (the "lower risk" group; n=370). The derived model correctly
      classified 85.3% of participants into the two groups and accounted for 71% of the
      variance in the latent HIV-related sexual behavior risk variable. The higher risk
      class also had worse scores on all hypothesized correlates (e.g., self-esteem,
      history of sexual assault or physical abuse) relative to the lower risk class.
      CONCLUSIONS: Sexual health clinics represent a unique point of access for HIV
      related sexual risk behavior intervention delivery by capitalizing on contact
      with adolescent girls when they present for services. Four empirically supported
      risk factors differentiated higher versus lower HIV risk. Replication of these
      findings is warranted and may offer an empirical basis for parsimonious screening
      recommendations for girls presenting for sexual healthcare services.

PMID- 24749897
TI  - Direct suppression as a mechanism for controlling unpleasant memories in daily
      life.
AB  - Suppressing unwanted memories can impair their later recall. Recent work shows
      that this forgetting is achieved by at least two mechanisms supported by distinct
      neural systems: thought substitution and direct suppression (Benoit & Anderson,
      2012). Here, we examined whether direct suppression, thought to be achieved by
      down-regulation of hippocampal activity, can disrupt memory of aversive scenes,
      and, if so, whether this disruption is linked to people's perception of their
      ability to control intrusive thoughts. We presented participants with strong
      naturalistic reminders to aversive scenes and asked them to either covertly
      retrieve or directly suppress the associated scenes. Later, participants were
      cued with the reminders and asked to recall the scenes in detail. Direct
      suppression reduced recall probability of the scenes and also reduced the number
      of details recalled, even when scenes were remembered. Deficits in recall arose
      for minor details but also for details central to each scene's gist. Participants
      with higher self-perceived control abilities over intrusive thoughts showed
      greater forgetting than did those reporting lower levels of control. These
      findings suggest that inhibitory processes underlying direct suppression can
      disrupt retention of aversive visual memories and link those processes to
      individual differences in control over intrusive thoughts in everyday life. These
      findings reinforce the possibility that inhibition may be less efficient in
      people likely to acquire posttraumatic stress disorder in the wake of a traumatic
      experience.

PMID- 24749898
TI  - Recent progress in the understanding and treatment of transthyretin amyloidosis.
AB  - WHAT IS KNOWN AND OBJECTIVE: Transthyretin (TTR) is a representative
      amyloidogenic protein in humans. Rate-limiting tetramer dissociation and rapid
      monomer misfolding and misassembly of variant TTR result in autosomal dominant
      familial amyloidosis. Analogous misfolding of wild-type TTR results in senile
      systemic amyloidosis (SSA) presenting as sporadic amyloid disease in the elderly.
      The objective of this review is to summarize recent progress in our understanding
      and treatment of TTR amyloidosis. METHODS: Literature searches were conducted on
      the topics of transthyretin, familial amyloid polyneuropathy and clinical trials,
      using PubMed, the United States clinical trials directory, pharmaceutical company
      websites and news reports. The information was collected, evaluated for relevance
      and quality, critically assessed and summarized. RESULTS AND DISCUSSION: The
      current standard first-line treatment of familial TTR amyloidosis is liver
      transplantation. However, large numbers of patients are not suitable transplant
      candidates. Recently, the clinical effects of TTR tetramer stabilizers, tafamidis
      and diflunisal, were demonstrated in randomized clinical trials, and tafamidis
      has been approved for the treatment of FAP in European countries and Japan. In
      addition, gene therapies with antisense oligonucleotides and small interfering
      RNAs are promising strategies to ameliorate TTR amyloidoses and are currently in
      clinical trials. WHAT IS NEW AND CONCLUSIONS: Liver transplantation to treat the
      familial TTR amyloidosis will likely be replaced by other less invasive
      therapies, such as TTR tetramer stabilizers and possibly gene therapy approaches.
      These newly developed therapies are expected to be effective for not only
      familial TTR amyloidosis but also SSA, based on their mechanisms of action.

PMID- 24749899
TI  - Meta-analysis of the effectiveness of smoking cessation interventions in
      community pharmacy.
AB  - WHAT IS KNOWN AND OBJECTIVE: With the emerging and promising role of healthcare
      professionals in implementing smoking cessation services, community pharmacists,
      in particular, can play a pivotal role. The aim of this meta-analysis is to
      evaluate the effectiveness of smoking cessation interventions delivered by
      community pharmacists in assisting smokers to quit. METHODS: PubMed, EMBASE,
      Scopus, International Pharmaceutical Abstracts and ISI Web of Knowledge were
      searched from inception to May 2013. Original research articles were selected for
      review, if they addressed the effectiveness of pharmacy-based interventions in
      smokers vs. a control group and reported smoking abstinence rates as an outcome.
      Obtained studies were assessed for methodological quality using the Cochrane
      Effective Practice and Organization of Care Group risk of bias tool. The primary
      outcome of measure was smoking abstinence based on the 'most rigorous criterion'.
      Pooled relative risks (RR) with 95% confidence interval (CI) were estimated using
      the Dersimonian and Laird random-effects models. Corresponding subgroup met
      analysis was performed. RESULTS: Of the 1168 articles extracted, five studies
      (three randomized controlled trials and two controlled before-after studies) met
      the inclusion criteria, involving a total of 1426 smokers. Pharmacist
      interventions showed better abstinence rates as compared with controls (RR 2.21,
      95% CI 1.49-3.29). Compared with the control group, the RR (95% CI) in the
      intervention group was 3.21 (1.81-5.72) for clinically validated abstinence and
      1.66 (1.08-2.54) for self-reported abstinence. In the intervention group, the RR
      for short-term and long-term abstinence was 2.48 (1.15-5.31) and 2.40 (1.37
      4.23), respectively. WHAT IS NEW AND CONCLUSIONS: Pharmacist-led interventions
      can significantly impact abstinence rates in smokers. Health policymakers should
      direct incentives for community pharmacists to provide such services.

PMID- 24749900
TI  - Experimental verification of structural alerts for the protein binding of sulfur
      containing compounds.
AB  - As often noted by Dr. Gilman Veith, a major barrier to advancing any model is
      defining its applicability domain. Sulfur-containing industrial organic chemicals
      can be grouped into several chemical classes including mercaptans (RSH), sulfides
      (RSR'), disulfides (RSSR'), sulfoxides (RS(=O)R'), sulfones (RS(=O)(=O)R'),
      sulfonates (ROS(=O)(=O)R') and sulfates (ROS(=O)(=O)OR'). In silico expert
      systems that predict protein binding reactions from 2D structure sub-divide these
      chemical classes into a variety of chemical reactive mechanisms and reactions
      which have toxic consequences. Using the protein binding profilers in version 3.1
      of the OECD QSAR Toolbox, a series of sulfur-containing chemicals were profiled
      for protein binding potential. From these results it was hypothesized which
      sulfur-containing chemicals would be reactive or non-reactive in an in chemico
      glutathione assay and whether if reactive they would exhibit toxicity in excess
      of baseline in the Tetrahymena pyriformis population growth impairment assay.
      Subsequently, these hypotheses were tested experimentally. The in chemico data
      show that the in silico profiler predictions were generally correct for all
      chemical categories, where testing was possible. Mercaptans could not be assessed
      for GSH reactivity because they react directly with the chromophore 5,5'
      dithiobis-(2-nitrobenzoic acid). With some exceptions, the major being
      disulfides, the in vitro toxicity data supported the in chemico findings. 

PMID- 24749901
TI  - NSAID use during pregnancy: maternal characteristics and prescription patterns:
      nationwide cohort study.

PMID- 24749902
TI  - Demographic, behavioural and physician-related determinants of early melanoma
      detection in a low-incidence population.
AB  - BACKGROUND: Knowledge of the factors that influence early detection of melanoma
      is important in developing strategies to reduce associated mortality. OBJECTIVES:
      To identify sociodemographic, behavioural and medical care-related factors
      associated with melanoma thickness in a low-incidence population but with a high
      case fatality. PATIENTS AND METHODS: In a multicentre, retrospective, survey
      based study of 202 patients with a recent diagnosis of invasive melanoma (< 1
      year), we collected data on demographic and behavioural factors, attitudes
      towards prevention, access to medical care, frequency of skin self-examination
      (SSE) and physician skin examination (PSE) in relation to melanoma thickness.
      RESULTS: Thinner tumours (<= 1 mm, 80 melanomas) were associated with female sex
      (P <= 0.049), nonnodular (superficial spreading melanoma, lentigo maligna
      melanoma, acral lentiginous melanoma) histological subtypes (P < 0.001), absence
      of ulceration (P <= 0.001), and location other than lower extremity or trunk
      location (P <= 0.004). Patients married at the time of diagnosis or who performed
      SSE during the year prior to diagnosis were more likely to have thinner tumours
      than those who did not [odds ratio (OR) 3.45, 95% confidence interval (CI) 1.48
      8.04 and OR 2.43, 95% CI 1.10-5.34, respectively]. Full-body skin examination by
      a physician was not significantly associated with thinner melanoma (OR 1.99, 95%
      CI 0.66-6.07). CONCLUSIONS: SSE was shown to be an important factor in the
      detection of thin melanoma, in contrast to partial or full-body PSE, which did
      not show any statistically significant effect on tumour thickness.

PMID- 24749903
TI  - Genome structure drives patterns of gene family evolution in ciliates, a case
      study using Chilodonella uncinata (Protista, Ciliophora, Phyllopharyngea).
AB  - In most lineages, diversity among gene family members results from gene
      duplication followed by sequence divergence. Because of the genome rearrangements
      during the development of somatic nuclei, gene family evolution in ciliates
      involves more complex processes. Previous work on the ciliate Chilodonella
      uncinata revealed that macronuclear beta-tubulin gene family members are
      generated by alternative processing, in which germline regions are alternatively
      used in multiple macronuclear chromosomes. To further study genome evolution in
      this ciliate, we analyzed its transcriptome and found that (1) alternative
      processing is extensive among gene families; and (2) such gene families are
      likely to be C. uncinata specific. We characterized additional macronuclear and
      micronuclear copies of one candidate alternatively processed gene family-a
      protein kinase domain containing protein (PKc)-from two C. uncinata strains.
      Analysis of the PKc sequences reveals that (1) multiple PKc gene family members
      in the macronucleus share some identical regions flanked by divergent regions;
      and (2) the shared identical regions are processed from a single micronuclear
      chromosome. We discuss analogous processes in lineages across the eukaryotic tree
      of life to provide further insights on the impact of genome structure on gene
      family evolution in eukaryotes. 

PMID- 24749904
TI  - Circumambulatory movement of negative charge ("ring walk") during gas-phase
      dissociation of 2,3,4-trimethoxybenzoate anion.
AB  - A dramatic "ortho effect" was observed during gas-phase dissociation of ortho-,
      meta-, and para-methoxybenzoate anions. Upon activation under mass spectrometric
      collisional activation conditions, anions generated from all three isomers
      undergo a CO2 loss. Of the m/z 107 ions generated in this way, only the 1-dehydro
      2-methoxybenzene anion from the ortho isomer underwent an exclusive formaldehyde
      loss. A peak for a formaldehyde loss in the spectra of 2,4-, 2,5-, and 2,6
      dimethoxybenzoates and the absence of an analogous peak from 3,4- and 3,5
      dimethoxy derivatives confirmed that this is a diagnostically useful ortho-isomer
      specific phenomenon. Moreover, the spectrum from 2,3-dimethoxybenzoic acid showed
      peaks for two consecutive formaldehyde losses. The 1-dehydro-2,3,4
      trimethoxybenzene anion (m/z 167) generated from 2,3,4-trimethoxybenzoate in this
      way endures three consecutive eliminations of formaldehyde units. For this, the
      negative charge, initially located on position 1, circumambulates to position 2,
      then to position 3, and finally to position 4 to form the final phenyl anion. The
      proposed stepwise fragmentation pathway, which resembles the well-known E1cB
      elimination mechanism, is supported by tandem mass spectrometric observations
      made with 2-[(13)C(2)H3]methoxy-3-[(13)C]methoxy-4-methoxybenzoic acid, and ab
      initio calculations. In addition, the spectra of ions such as 1-dehydro-3,4
      dimethoxybenzene anion show peaks for consecutive methyl radical losses, a
      feature that establishes the 1,2-relationship between the two methoxy groups. 

PMID- 24749905
TI  - Photothermal microscopy: optical detection of small absorbers in scattering
      environments.
AB  - Photothermal microscopy enables detection of nanometer-sized objects solely based
      on their absorption. This technique allows efficient observation of various nano
      objects in scattering media notably gold nanoparticles in cells. The extreme
      sensitivity of the method and the stability of the signals open numerous
      applications in spectroscopy, analytical chemistry and bioimaging. This review
      briefly describes the principle and the main characteristics of photothermal
      microscopy, with its major advantages and limitations, and exposes the principal
      applications that have been carried out since its first implementation. 

PMID- 24749906
TI  - Influence of pH, concentration of sodium lactate as an additive and ultrasonic
      treatment on synthesis of zinc phosphate white pigments.
AB  - Zinc oxide that has the photocatalytic activity is used as a white pigment for
      cosmetics. A certain degree of sebum on the skin is decomposed by the ultraviolet
      radiation in sunlight. In this work, zinc phosphates were prepared from zinc
      nitrate and phosphoric acid at pH 5 and 7 with and without the addition of sodium
      lactate and ultrasonic treatment as a novel white pigment for use in cosmetics.
      The chemical composition, powder properties, photocatalytic activity, colour
      phase, moisture retention and smoothness of the zinc phosphates were studied. The
      obtained materials had a Zn/P ratio of about 1.5, which corresponds to zinc
      orthophosphate Zn3 (PO4 )2 . Samples prepared with ultrasonic treatment indicated
      the high ratios of large particles in scanning electron microscopy images and
      particle-size distributions. The photocatalytic activity of these zinc phosphate
      particles was too less to protect the sebum on the skin. The materials obtained
      and their thermal products at 100 degrees C showed a high reflectance within the
      range of visible light. The slipping resistance and roughness of the powder were
      enough low for use in cosmetics. 

PMID- 24749907
TI  - ADRB1 and ADBR2 gene polymorphisms and the ocular hypotensive response to topical
      betaxolol in healthy Mexican subjects.
AB  - BACKGROUND: The beta adrenergic receptors (ADRB) are expressed in the ciliary
      body and trabecular meshwork, structures involved in aqueous humor production and
      outflow, respectively. ADRB are members of the adrenergic family of G-protein
      coupled receptors. Topic beta blockers have a good local and systemic tolerance;
      they reduce the aqueous humor production and eye strain blocking the ADRB of the
      ciliary body and interfering with adenylate cyclase. However, the ocular
      hypotensive response is not the same in all patients and could be mediated by the
      polymorphisms of the ADRB genes. MATERIALS AND METHODS: Seventy-two healthy
      subjects were studied after treatment with topical betaxolol in both eyes. We
      analyzed ADRB1 and ADRB2 gene polymorphisms by PCR and automated DNA sequencing.
      RESULTS: There was statistically significant difference between baseline
      intraocular pressure (IOP) and final IOP of both eyes (baseline IOP 16.2 +/- 1.2 
      follow-up IOP 13.6 +/- 2.0 (mean difference-2.5 +/- 1.3, p < 0.001). Gly389 had
      a higher baseline IOP than Arg389 (17.0 +/- 1.2 mmHg versus 16.0 +/- 1.2 mmHg; p
      = 0.02), and conversely Arg389 had a greater magnitude of response than Gly389 to
      betaxolol therapy (-2.9 +/- 1.1 mmHg versus -0.7 +/- 0.4 mmHg; p < 0.001). Gln27
      had a higher response than Glu27 (-2.7 +/- 1.3 mmHg versus -1.9 +/- 1.0; p =
      0.02). CONCLUSION: Arg389 polymorphism of the ADRB1 gene and Gln27 polymorphism
      of the ADRB2 gene were associated with the hypotensive response to topic
      betaxolol in healthy Mexican volunteers.

PMID- 24749908
TI  - Reducing uncertainty in calibrating aquifer flow model with multiple scales of
      heterogeneity.
AB  - Modeling and calibration of natural aquifers with multiple scales of
      heterogeneity is a challenging task due to limited subsurface access. While
      computer modeling plays an essential role in aquifer studies, large uncertainty
      exists in developing a conceptual model of an aquifer and in calibrating the
      model for decision making. Due to uncertainties such as a lack of understanding
      of subsurface processes and a lack of techniques to parameterize the subsurface
      environment (including hydraulic conductivity, source/sink rate, and aquifer
      boundary conditions), existing aquifer models often suffer nonuniqueness in
      calibration, leading to poor predictive capability. A robust calibration
      methodology is needed that can address the simultaneous estimations of aquifer
      parameters, source/sink, and boundary conditions. In this paper, we propose a
      multistage and multiscale approach that addresses subsurface heterogeneity at
      multiple scales, while reducing uncertainty in estimating the model parameters
      and model boundary conditions. The key to this approach lies in the appropriate
      development, verification, and synthesis of existing and new techniques of static
      and dynamic data integration. In particular, based on a given set of observation
      data, new inversion techniques can be first used to estimate aquifer large-scale
      effective parameters and smoothed boundary conditions, based on which parameter
      and boundary condition estimation can be refined at increasing detail using
      standard or highly parameterized estimation techniques. 

PMID- 24749909
TI  - Urinary 8-hydroxy-2'-deoxyguanosine (8-oxodG) level can predict acute renal
      damage in young children with urinary tract infection.
AB  - BACKGROUND: There are no good biomarkers to predict renal parenchymal involvement
      in children with urinary tract infection (UTI). METHODS: Children (N = 73)
      younger than 5 years with UTI were enrolled. Urinary levels of 8-hydroxy-2'
      deoxyguanosine (8-oxodG) and total antioxidant capacity (TAC) were checked as
      markers of oxidative stress and antioxidant capacity, respectively. Tc99m
      dimercaptosuccinic acid (DMSA) renal scintigraphy was used to find evidence of
      renal involvement. RESULTS: Patients with positive DMSA findings had higher
      levels of urinary 8-oxodG (p = 0.003) and higher urinary TAC (p = 0.001) than
      patients with normal DMSA findings. CONCLUSIONS: High level of urinary 8-oxodG
      may be a risk factor of severe renal damage.

PMID- 24749910
TI  - Are endothelial microparticles early markers of pulmonary hypertension?
AB  - OBJECTIVE: To find out the relation between endothelial microparticles (EMPs),
      pulmonary arterial stiffness and thickness of pulmonary artery intima media to
      determine the prognosis of Eisenmenger syndrome and their correlation with
      echocardiographic and hemodynamic parameters. METHODS: Sixteen patients with
      Eisenmenger syndrome and 37 control patients were included. Electron
      microparticles levels, angiographic and echocardiographic findings were compared.
      RESULTS: Thickness of pulmonary arterial intima media and systolic and diastolic
      diameters of pulmonary artery were found significant in the patient group. CD144
      and CD146 EMP values of patient group were statistically high. However, there was
      not any significant difference in pulmonary arterial strain, elasticity and
      stiffness. Positive significant relationship was found between pulmonary artery
      intima media thickness and CD144 in patient group. But there was not any
      significance between CD 146 and pulmonary artery intimamedia thickness.
      CONCLUSIONS: Invasive methods remain as the gold standard for pulmonary
      hypertension diagnosis, follow-up and treatment, but it is risky and can even be
      fatal. Our study showed that EMPs, thickness of pulmonary artery intima media and
      pulmonary stiffness could be novel noninvasive modalities for the follow-up
      pulmonary hypertensive patients.

PMID- 24749912
TI  - Decreased serum heat shock protein 60 levels in newly diagnosed immune
      thrombocytopenia patients.
AB  - Immune thrombocytopenia (ITP) is an autoimmune disease characterized by
      peripheral thrombocyte destruction. In some autoimmune disorders, heat-shock
      proteins (HSP) are suggested to be an important antigenic factor. In this study,
      we demonstrated the serum free levels of HSP60, HSP70, anti-HSP60, and anti-HSP70
      in ITP patients and healthy controls. Twenty-eight newly diagnosed ITP patients,
      35 ITP patients in chronic phase, and 25 healthy controls were enrolled to this
      study. Serum levels of HSP60, HSP70, anti-HSP60, and anti-HSP70 were determined
      by the ELISA method. Serum HSP60 levels of newly diagnosed ITP patients were
      significantly decreased when compared with both chronic phase ITP patients and
      healthy controls. HSP60 levels of ITP patients (both newly diagnosed and chronic
      phase) with thrombocyte counts more than 30 * 10(9)/L were significantly
      increased compared with ITP patients with thrombocyte counts less than 30 *
      10(9)/L and there was a positive correlation between thrombocyte counts and serum
      free HSP60 levels in ITP patients. This is the first study demonstrating the
      extracellular HSP levels in adult ITP patients. HSPs are shown to have a place in
      the pathogenesis of many autoimmune disorders. Low level of HSP60 may lead to
      lack of anti-inflammatory response due to less Treg activation, hence, could be a
      counterpart in the pathogenesis of ITP. Further studies are needed to understand
      the role of HSPs in the pathogenesis of ITP and whether they can be used for
      diagnosis, prognosis, and treatment of ITP. 

PMID- 24749911
TI  - Collapse of a long axis: single-molecule Forster resonance energy transfer and
      serpin equilibrium unfolding.
AB  - The energy required for mechanical inhibition of target proteases is stored in
      the native structure of inhibitory serpins and accessed by serpin structural
      remodeling. The overall serpin fold is ellipsoidal with one long and two short
      axes. Most of the structural remodeling required for function occurs along the
      long axis, while expansion of the short axes is associated with misfolded,
      inactive forms. This suggests that ellipticity, as typified by the long axis, may
      be important for both function and folding. Placement of donor and acceptor
      fluorophores approximately along the long axis or one of the short axes allows
      single-pair Forster resonance energy transfer (spFRET) to report on both
      unfolding transitions and the time-averaged shape of different conformations.
      Equilibrium unfolding and refolding studies of the well-characterized inhibitory
      serpin alpha1-antitrypsin reveal that the long axis collapses in the folding
      intermediates while the monitored short axis expands. These energetically
      distinct intermediates are thus more spherical than the native state. Our spFRET
      studies agree with other equilibrium unfolding studies that found that the region
      around one of the beta strands, s5A, which helps define the long axis and must
      move for functionally required loop insertion, unfolds at low denaturant
      concentrations. This supports a connection between functionally important
      structural lability and unfolding in the inhibitory serpins. 

PMID- 24749914
TI  - The consequences of randomizing schools rather than children.

PMID- 24749915
TI  - Cicutto, To, and Murphy respond: a randomized controlled trial of a public health
      nurse-delivered asthma program to elementary schools.

PMID- 24749913
TI  - Hemorrhage-induced interleukin-1 receptor pathway in lung is suppressed by 3,5
      bis(2-fluorobenzylidene)-4-piperidone in a rat model of hypovolemic shock.
AB  - Severe blood loss in victims of trauma creates an exaggerated inflammatory
      background that contributes to the development of intravascular coagulopathy and
      multiple organ dysfunction syndrome. We hypothesized that treatment with
      diphenyldifluoroketone EF24, an inhibitor of nuclear factor kappa-B, would have
      salutary effects in hemorrhagic shock. The objective of this study was to
      investigate the effect of EF24 on the expression of the interleukin-1 receptor
      (IL-1R) superfamily in a rat model of hypovolemic shock. Hypovolemia was induced
      by gradually withdrawing approximately 50% of circulating blood, and EF24 was
      administered intraperitoneally (0.2 mg/kg) in 50 MUL of saline. After 6 h of
      shock, lung tissue was probed immunohistochemically and by immunoblotting to
      study the expression of Toll-like receptor 4 (TLR4), IL-1R, suppression of
      tumorigenicity 2 (ST2), and single immunoglobulin IL-1R-related (SIGIRR). The
      tissue-associated pro-inflammatory cytokines, tumor necrosis factor alpha (TNF
      alpha) and IL-6, were measured by enzyme-linked immunosorbent assay. We observed
      a reduction in immunoreactive TLR4 and IL-1R1 in lung tissue of rats treated with
      EF24. Simultaneously, the pulmonary expression of ST2 and SIGIRR (the putative
      down-regulators of the pro-inflammatory IL-1R pathway) was increased in EF24
      treated hemorrhaged rats. The concentration of hemorrhage-induced TNF-alpha and
      IL-6 in lung tissue homogenates was also reduced by EF24 treatment. These results
      confirm our previous in vitro observations in lipopolysaccharide-stimulated
      dendritic cells that EF24 beneficially modulates the IL-1R pathway and suggest
      that it could be investigated as an adjunct therapeutic in managing inflammation
      associated with hemorrhagic shock. 

PMID- 24749916
TI  - Matching the pace of genomic advances through the integration of genomic
      education into high school health education.

PMID- 24749917
TI  - Effect of food service nutrition improvements on elementary school cafeteria
      lunch purchase patterns.
AB  - BACKGROUND: Schools can play a major role in prevention and intervention for
      childhood obesity. We describe changes in elementary school cafeteria lunch sales
      patterns resulting from nutritional improvements in menu offerings that were part
      of a community-wide focus on health. METHODS: Elementary school lunch sales data
      were collected for 1 week in each of 7 years in a district serving a
      predominantly poor, rural, and Caucasian student population, with high rates of
      obesity. Post hoc data analyses described lunch sales patterns and related food
      service costs over the project years. RESULTS: The percentage of high calorie/low
      nutrition foods sold decreased from 22% of all sales in 2005 to 0% in 2011. High
      calorie snack purchases decreased from 535 items to 0 items. The sale of fresh
      fruits increased by 12%. There was only a slight decline in the percentage of
      children who purchased cafeteria lunches over the years and a 15.2% cost increase
      for purchasing healthier food supplies. CONCLUSIONS: Elementary school children
      purchased healthier lunches when healthier menu items were offered and when less
      healthy foods were eliminated from the menu. There was no significant decline in
      the number of students who purchased lunches as nutritional improvements were
      made.

PMID- 24749918
TI  - Correlates of high school freshman girls' reported reasons for engaging in sexual
      intercourse.
AB  - BACKGROUND: Intrapersonal and external factors, including social pressures and
      the desire for acceptance from peers, influence sexual activity among
      adolescents. This study examined how personal characteristics, risky behaviors,
      normative beliefs, household factors, and engagement in extracurricular
      activities were related to high school freshman girls' reported reasons for
      having sexual intercourse. METHODS: Baseline data were analyzed from 158 girls
      enrolled in high school-based abstinence-only-until-marriage education programs
      during their freshman year. Binary logistic regression was performed to identify
      factors associated with Pressures and Reasons for Engaging in Sex Scale (PRESS)
      scores. RESULTS: Results indicate that girls with high PRESS scores were
      significantly more likely to have had sex (OR = 4.29), consumed alcohol within
      the previous year (OR = 6.13), reported strict household rules (OR = 1.49), and
      thought more girls their age had sex (OR = 1.67). CONCLUSION: School- and family
      based interventions should be developed to encourage and strengthen parent-teen
      communication within the household and reinforce self-worth and positive self
      perceptions among adolescent girls.

PMID- 24749919
TI  - Opportunities for increasing human papillomavirus vaccine provision in school
      health centers.
AB  - BACKGROUND: Uptake of human papillomavirus (HPV) vaccine remains low among
      adolescents in the United States. We sought to assess barriers to HPV vaccine
      provision in school health centers to inform subsequent interventions. METHODS:
      We conducted structured interviews in the fall of 2010 with staff from all 33
      school health centers in North Carolina that stocked HPV vaccine. RESULTS:
      Centers had heterogeneous policies and procedures. Out-of-pocket costs for
      children and youth to receive privately purchased HPV vaccine were a key barrier
      to providing HPV vaccine within school health centers. Other barriers included
      students not returning consent forms, costs to clinics of ordering and stocking
      privately purchased HPV vaccine, and difficulty using the statewide immunization
      registry. Most (82%) school health centers were interested in hosting
      interventions to increase HPV vaccine uptake, especially those that the centers
      could implement themselves, but many had limited staff to support such efforts.
      Activities rated as more likely to raise HPV vaccine uptake were student
      incentives, parent reminders, and obtaining consent from parents while they are
      at school (all ps < .05). CONCLUSIONS: Although school health centers reported
      facing several key barriers to providing HPV vaccine, many were interested in
      partnering with outside organizations on low-cost interventions to increase HPV
      vaccine uptake among adolescents.

PMID- 24749920
TI  - Feasibility of providing sexually transmitted infection testing and treatment in
      off-campus, nonclinic settings for adolescents enrolled in a school-based
      research project.
AB  - BACKGROUND: This study examined the acceptability and feasibility of using a
      biological outcome measure to evaluate a school-based sexuality education
      program. Confidential field-delivered sexually transmitted infection (STI)
      testing by nonmedical field staff and STI treatment by medically trained field
      staff was assessed in off-campus and off-clinic settings for adolescents enrolled
      in the trial. METHODS: After parental and adolescent consent were obtained, a
      convenient time and location was identified to collect urine to test for
      chlamydia (Chlamydia trachomatis, CT), gonorrhea (Neisseria gonorrheae, NG), and
      trichomonas (Trichomonas vaginalis, TV) infection and to treat students with
      positive results. RESULTS: A total of 391 of 1742 students had permission to
      participate (22%); 353 (90%) provided urine samples; 28 (8%) had positive test
      results: CT(18), NG(5), and TV(8). Testing and treatment occurred at home for 92%
      and 59% of students, respectively; on weekdays (for 69% and 96%, respectively)
      and between noon and 8 pm (for 76% and 88%, respectively). All students who
      tested positive were treated. Several lessons and strategies that may improve the
      likelihood that students will participate in field-delivered STI testing and
      treatment emerged. CONCLUSION: STI testing and treatment are feasible for
      students enrolled in a school-based sexuality education program. However,
      obtaining parental consent may be challenging.

PMID- 24749921
TI  - Sex differences in associations of school connectedness with adolescent sexual
      risk-taking in Nova Scotia, Canada.
AB  - BACKGROUND: Associations of lower school connectedness have been seen with
      adolescent sexual risk behaviors, but little is known about gender differences
      with respect to these relationships. Understanding any such differences could
      contribute to better supporting the school environment to promote youth sexual
      health. METHODS: We used provincially representative cross-sectional data from
      1415 sexually active students in grades 10 to 12 in Nova Scotia, Canada, to
      determine whether lower school connectedness was associated with students' sexual
      risk behaviors using multivariate logistic regression, stratifying by sex.
      RESULTS: In boys, lower connectedness was associated with three risk behaviors,
      having  >= 2 partners in the previous year (odds ratio [OR] 1.07; 95% confidence
      interval [CI] 1.01-1.13), no condom use at last intercourse (OR 1.06; 95% CI 1.01
      1.12), and having unplanned intercourse due to substance use (OR 1.09; 95% CI
      1.03-1.15). No such associations were seen in girls. CONCLUSIONS: These results
      demonstrate that gender differences may exist for associations of school
      connectedness and sexual risk behaviors; connectedness may be more important for
      boys than for girls in this area of adolescent health. Educators should consider
      gender differences when designing interventions to maximize youth sexual health
      through school-based interventions. Further research on school connectedness and
      risk-taking should examine genders separately.

PMID- 24749922
TI  - Improving sexuality education: the development of teacher-preparation standards.
AB  - BACKGROUND: Teaching sexuality education to support young people's sexual
      development and overall sexual health is both needed and supported. Data continue
      to highlight the high rates of teen pregnancy, sexually transmitted disease,
      including human immunodeficiency virus (HIV) infections, among young people in
      the United States as well as the overwhelming public support for sexuality
      education instruction. In support of the implementation of the National Sexuality
      Education Standards, the current effort focuses on better preparing teachers to
      deliver sexuality education. METHODS: An expert panel was convened by the Future
      of Sex Education Initiative to develop teacher-preparation standards for
      sexuality education. Their task was to develop standards and indicators that
      addressed the unique elements intrinsic to sexuality education instruction.
      RESULTS: Seven standards and associated indicators were developed that address
      professional disposition, diversity and equity, content knowledge, legal and
      professional ethics, planning, implementation, and assessment. CONCLUSIONS: The
      National Teacher-Preparation Standards for Sexuality Education represent an
      unprecedented unified effort to enable prospective health education teachers to
      become competent in teaching methodology, theory, practice of pedagogy, content,
      and skills, specific to sexuality education. Higher education will play a key
      role in ensuring the success of these standards.

PMID- 24749923
TI  - Optimization of antitrypanosomatid agents: identification of nonmutagenic drug
      candidates with in vivo activity.
AB  - Chagas disease, caused by Trypanosoma cruzi parasite, was described thousands of
      years ago. Currently, it affects millions of people, mostly in Latin America, and
      there are not suitable drugs for treating it. As an attempt to find appropriate
      drugs to deal with this problem, we report here on the design, synthesis, and
      characterization of 82 new compounds. Trypanosomicidal behavior in vitro showed
      more than 20 outstanding derivatives with anti-Trypanosoma cruzi activity.
      Furthermore, we studied the nonspecific toxicity against mammalian cells
      determining their selectivity and also performed mutagenicity studies. Proof of
      concept, in vivo studies, was conducted with two of the most promising
      derivatives (77 and 80). They were identified as candidates because they have (i)
      very simple and cost-effective syntheses; (ii) activity against different stages
      and strains of the parasite showing excellent in vivo behavior during the acute
      phase of Chagas disease; and (iii) neither nonspecific toxicity nor mutagenic
      activity. 

PMID- 24749924
TI  - NLR's and left-atrial thrombus in patients with non-valvular atrial fibrillation.

PMID- 24749925
TI  - Cardiac resynchronization therapy: the state of the art.
AB  - A strong body of evidence exists to support cardiac resynchronization therapy
      (CRT) as a mainstay in the management of advanced heart failure for patients with
      LBBB-type QRS prolongation. Progress in technology has made percutaneous CRT
      easier to achieve. Skillful operators can readily reach implantation success
      rates in excess of 95%. Nevertheless, not every patient selected for CRT,
      according to current criteria, benefits from this therapy. Several factors
      contribute to the lack of benefit in these patients, including inadequate patient
      selection, lack of control of atrial arrhythmias, procedural factors and
      suboptimal pacemaker settings. It remains to be seen whether newer technology and
      pacing algorithms will increase response rates to CRT. The focus of this review
      will be to examine which patients benefit most from CRT and to assess methods for
      optimizing patient selection in order to achieve maximum benefit from this
      pivotal therapy. 

PMID- 24749926
TI  - The immune injury effects and clinical significance of eosinophils in auto-immune
      related hematocytopenia.
AB  - Eosinophils (EOS) quantity, active state, peroxidase activity (POX), and HLA-DR
      expression in bone marrow of 176 Auto-Immune-Related Hematocytopenia (AIRH)
      patients were analyzed. Immunofluorescent staining (IF) is performed to observe
      the expression of immunizing molecules on EOS. In serum of AIRH patients the
      levels of IL-4, IL-5, IL-6, IL-12, IL-17, and IFN- gamma were increased but there
      was no significance on IL-2 level. In marrow of AIRH, activated EOS expressed
      POX, and other molecules, it played various cell-mediated immunity injury roles
      to hemocyte. EOS might be possessed with multiple immunological fuctions, it
      playes an important immune effect in AIRH autoimmune pathological processes.

PMID- 24749927
TI  - Pore-scale investigation of micron-size polyacrylamide elastic microspheres
      (MPEMs) transport and retention in saturated porous media.
AB  - Knowledge of micrometer-size polyacrylamide elastic microsphere (MPEM) transport
      and retention mechanisms in porous media is essential for the application of
      MPEMs as a smart sweep improvement and profile modification agent in improving
      oil recovery. A transparent micromodel packed with translucent quartz sand was
      constructed and used to investigate the pore-scale transport, surface deposition
      release, and plugging deposition-remigration mechanisms of MPEMs in porous media.
      The results indicate that the combination of colloidal and hydrodynamic forces
      controls the deposition and release of MPEMs on pore-surfaces; the reduction of
      fluid salinity and the increase of Darcy velocity are beneficial to the MPEM
      release from pore-surfaces; the hydrodynamic forces also influence the
      remigration of MPEMs in pore-throats. MPEMs can plug pore-throats through the
      mechanisms of capture-plugging, superposition-plugging, and bridge-plugging,
      which produces resistance to water flow; the interception with MPEM particulate
      filters occurring in the interior of porous media can enhance the plugging effect
      of MPEMs; while the interception with MPEM particulate filters occurring at the
      surface of low-permeability layer can prevent the low-permeability layer from
      being damaged by MPEMs. MPEMs can remigrate in pore-throats depending on their
      elasticity through four steps of capture-plugging, elastic deformation, steady
      migration, and deformation recovery. 

PMID- 24749928
TI  - A case of high-titer anti-D hemolytic disease of the newborn in which late onset
      and mild course is associated with the D variant, RHD-CE(9)-D.
AB  - BACKGROUND: The RhD antigen is very immunogenic and is a significant cause of
      hemolytic disease of the newborn (HDN). The RHD-CE(8-9)-D hybrid allele is
      commonly associated with a D- phenotype. Here, we report a case of high-titer
      maternal anti-D and late onset of HDN in a newborn carrying a RHD-CE(9)-D variant
      supposedly encoding the same partial D antigen as the RHD-CE(8-9)-D allele, but
      with significant expression of D antigen. STUDY DESIGN AND METHODS: To elucidate
      the blood group antigen background of the case, we carried out serologic, flow
      cytometric, and genetics studies of the newborn and his father. CONCLUSION:
      Individuals carrying the RHD-CE(9)-D allele do express D antigen, but do so at
      significantly lower levels than those carrying the more common D+ phenotypes
      (e.g., DCe/dce). It may mitigate and delay otherwise severe HDN in pregnancies
      complicated by high-titer anti-D.

PMID- 24749929
TI  - Predictors and processes associated with home-based family therapists'
      professional quality of life.
AB  - This study examined whether home-based family therapists' (HBFT) workload and
      clinical experience were associated with therapists' professional quality of life
      directly and indirectly through self-care activities and frequency of clinical
      supervision. Hypotheses were tested using structural equation modeling with a
      sample of 225 home-based therapists. Results suggested that therapists' workload
      and HBFT experience significantly predicted therapists' professional quality of
      life. These associations between therapists' workload and HBFT experience were
      partially mediated through participation in self-care and frequency of clinical
      supervision. Implications for improving therapists' quality of life are discussed
      as a function of therapists' workload, clinical experience, self-care, and
      supervision. 

PMID- 24749930
TI  - The role of cognitive styles and sociodemographic characteristics in consumer
      perceptions and attitudes toward nonhuman animal welfare.
AB  - Given the increasing importance of exploring consumers' concerns about the
      welfare of farmed animals, a survey questionnaire was designed to investigate the
      role of cognitive styles along with sociodemographic characteristics in
      consumers' perceptions about nonhuman animal welfare (AW) and their willingness
      to pay for animal-friendly products. The results revealed that the survey
      respondents were concerned about AW and had negative perceptions of the way
      animals were treated. They showed positive attitudes toward some actions to be
      taken for improving AW and strongly agreed to pay more for animal-friendly
      products. Consistent with previous studies, results revealed significant
      associations between sociodemographics and concern toward AW. However, some
      observed differences were highlighted by cognitive styles rather than by
      sociodemographic characteristics. These results indicate a significant link
      between cognitive styles and perceptions and attitudes toward AW, which may
      outweigh previously found sociodemographic differences and fuel the contemporary
      debate on AW. 

PMID- 24749931
TI  - Psychometric evaluation of a direct observation of procedural skills assessment
      tool for ultrasound-guided regional anaesthesia.
AB  - Assessment tools must be investigated for reliability, validity and feasibility
      before being implemented. In 2013, the Australian and New Zealand College of
      Anaesthetists introduced workplace-based assessments, including a direct
      observation of a procedural skills assessment tool. The objective of this study
      was to evaluate the psychometric properties of this assessment tool for
      ultrasound-guided regional anaesthesia. Six experts assessed 30 video-recorded
      trainee performances of ultrasound-guided regional anaesthesia. Inter-rater
      reliability, assessed using absolute agreement intraclass correlation
      coefficients, varied from 0.10 to 0.49 for the nine individual nine-point scale
      items, and was 0.25 for a 'total score' of all items. Internal consistency was
      measured by correlation between 'total score' and 'overall performance' scale
      item (r = 0.68, p < 0.001). Construct validity was demonstrated by the 'total
      score' correlating with trainee experience (r = 0.51, p = 0.004). The mean time
      taken to complete assessments was 6 min 35 s.

PMID- 24749932
TI  - Cu-catalyzed skeletal rearrangement of O-propargylic electron-rich arylaldoximes
      into amidodienes.
AB  - O-Propargylic oximes that possess an electron-rich p-(dimethylamino)phenyl group
      at the oxime moiety and an alkyl group at the propargylic position were
      efficiently converted in the presence of Cu(I) catalysts to the corresponding 1
      amidodienes in good to excellent yields. The reaction proceeded via a 2,3
      rearrangement, followed by isomerization of the resulting N-allenylnitrone to the
      amide, presumably through the oxaziridine intermediate. 

PMID- 24749933
TI  - Plasma micro-nanotextured, scratch, water and hexadecane resistant,
      superhydrophobic, and superamphiphobic polymeric surfaces with perfluorinated
      monolayers.
AB  - Superhydrophobic and superamphiphobic toward superoleophobic polymeric surfaces
      of polymethyl methacrylate (PMMA), polyether ether ketone (PEEK), and
      polydimethyl siloxane (PDMS) are fabricated in a two-step process: (1) plasma
      texturing (i.e., ion-enhanced plasma etching with simultaneous roughening), with
      varying plasma chemistry depending on the polymer, and subsequently (2) grafting
      of self-assembled perfluorododecyltrichlorosilane monolayers (SAMs). Depending on
      the absence or not of an etch mask (i.e., colloidal microparticle self-assembly
      on it), random or ordered hierarchical micro-nanotexturing can be obtained. We
      demonstrate that stable organic monolayers can be grafted onto all these textured
      polymeric surfaces. After the monolayer deposition, the initially hydrophilic
      polymeric surfaces become superamphiphobic with static contact angles for water
      and oils>153 degrees , for hexadecane>142 degrees , and hysteresis<10 degrees 
      for all surfaces. This approach thus provides a simple and generic method to
      obtain superamphiphobicity on polymers toward superoleophobicity. Hydrolytic and
      hexadecane immersion tests prove that superamphiphobicity is stable for more than
      14 days. We also perform nanoscratch and post nanoscratch tests to prove the
      scratch resistance of both the texture and the SAM and demonstrate lower
      coefficient of friction of the SAM compared to the uncoated surface. Scanning
      electron microscope observation after the nanoscratch tests confirms the scratch
      resistance of the surfaces.

PMID- 24749934
TI  - There is more than "more is up": Hand and foot responses reverse the vertical
      association of number magnitudes.
AB  - Recent research in cognitive sciences shows a growing interest in spatial
      numerical associations. The horizontal SNARC (spatial-numerical association of
      response codes) effect is defined by faster left-sided responses to small numbers
      and faster right-sided responses to large numbers in a parity judgment task. In
      this study we investigated whether there is also a SNARC effect for upper and
      lower responses. The grounded cognition approach suggests that the universal
      experience of "more is up" serves as a robust frame of reference for vertical
      number representation. In line with this view, lower hand responses to small
      numbers were faster than to large numbers (Experiment 1). Interestingly, the
      vertical SNARC effect reversed when the lower responses were given by foot
      instead of the hand (Experiments 2, 3, and 4). We found faster upper (hand)
      responses to small numbers and faster lower (foot) responses to large numbers.
      Additional experiments showed that spatial factors cannot account for the
      reversal of the vertical SNARC effect (Experiments 4 and 5). Our results question
      the view of "more is up" as a robust frame of reference for spatial-numerical
      associations. We discuss our results within a hierarchical framework of numerical
      cognition and point to a possible link between effectors and number
      representation.

PMID- 24749935
TI  - Visual speech acts differently than lexical context in supporting speech
      perception.
AB  - The speech signal is often badly articulated, and heard under difficult listening
      conditions. To deal with these problems, listeners make use of various types of
      context. In the current study, we examine a type of context that in previous work
      has been shown to affect how listeners report what they hear: visual speech
      (i.e., the visible movements of the speaker's articulators). Despite the clear
      utility of this type of context under certain conditions, prior studies have
      shown that visually driven phonetic percepts (via the "McGurk" effect) are not
      "real" enough to affect perception of later-occurring speech; such percepts have
      not produced selective adaptation effects. This failure contrasts with successful
      adaptation by sounds that are generated by lexical context-the word that a sound
      occurs within. We demonstrate here that this dissociation is robust, leading to
      the conclusion that visual and lexical contexts operate differently. We suggest
      that the dissociation reflects the dual nature of speech as both a perceptual
      object and a linguistic object. Visual speech seems to contribute directly to the
      computations of the perceptual object but not the linguistic one, while lexical
      context is used in both types of computations.

PMID- 24749936
TI  - A variant within intron 1 of the PTPN22 gene decreases the genetic susceptibility
      of ankylosing spondylitis in a central south Chinese Han population.
AB  - OBJECTIVES: The protein tyrosine phosphatase non-receptor type 22 (PTPN22) is
      generally accepted as a key factor in maintaining immune cellular homeostasis. So
      far, no association has been reported between the polymorphisms of PTPN22 and
      ankylosing spondylitis (AS) in Chinese populations. We attempted to explore the
      association between the PTPN22 gene and AS in a central south Chinese Han
      population. METHOD: Our study involved 180 HLA-B27(+) unrelated patients and 360
      HLA-B27(-) healthy individuals. Seven single nucleotide polymorphisms (SNPs:
      rs2476601, rs1217414, rs1217418, rs1746853, rs1970559, rs3765598, and rs3811021)
      were detected. Genotyping was conducted using the polymerase chain reaction (PCR)
      restriction fragment length polymorphism (RFLP) method. RESULTS: rs2476601 was
      not polymorphic enough in both patients and controls. The SNP rs1217414 was found
      to be associated with AS but the other five of the seven selected SNPs
      (rs1217418, rs1746853, rs1970559, rs3765598 and rs3811021) were not. CONCLUSIONS:
      The PTPN22 gene might be associated with AS in a central south Chinese Han
      population.

PMID- 24749938
TI  - Dermoscopic criteria associated with BRAF and NRAS mutation status in primary
      cutaneous melanoma.
AB  - BACKGROUND: The identification of BRAF mutations in melanoma led to the
      development and implementation of new and effective therapies. Few clinical and
      histological features have been associated with this mutational status.
      OBJECTIVES: The main objective of this study was to investigate clinical,
      histopathological and dermoscopic characteristics of primary melanomas according
      to BRAF or NRAS mutational status. METHODS: An observational retrospective study
      including melanoma dermoscopy images assessed for somatic mutations in BRAF and
      NRAS. RESULTS: Seventy-two patients were included, 30 women (42%) and 42 men
      (58%), mean age was 59 +/- 15.51 years. BRAF-mutated melanomas were more
      frequently located on the trunk (n = 18, 64% for BRAF-mutated vs. n = 11, 29% for
      wild-type melanomas, P = 0.013). Histological ulceration was associated with the
      presence of BRAF mutations [odds ratio (OR) 3.141; 95% confidence interval (CI)
      1.289-7.655; P = 0.002]. The Breslow index tended to be thicker in BRAF-mutated
      compared with wild-type (P = 0.086). BRAF mutations were present in 28 (39%)
      patients and only four cases were positive for NRAS mutations (6%), BRAF and NRAS
      mutations being mutually exclusive. The presence of dermoscopic peppering was
      associated with MAPK mutations (BRAF and NRAS) (OR 1.68; 95% CI 1.089-2.581; P =
      0.015). Dermoscopic ulceration was also associated with BRAF mutations excluding
      acral and facial melanomas (OR 2.64; 95% CI 1.032-6.754). CONCLUSIONS: This study
      showed a correlation between BRAF and NRAS status and dermoscopic findings of
      'peppering' as an expression of regression and melanophages in the dermis,
      suggesting a morphological consequence of immune behaviour in BRAF-mutated
      melanomas.

PMID- 24749939
TI  - Hydraulic tomography offers improved imaging of heterogeneity in fractured rocks.
AB  - Fractured rocks have presented formidable challenges for accurately predicting
      groundwater flow and contaminant transport. This is mainly due to our difficulty
      in mapping the fracture-rock matrix system, their hydraulic properties and
      connectivity at resolutions that are meaningful for groundwater modeling. Over
      the last several decades, considerable effort has gone into creating maps of
      subsurface heterogeneity in hydraulic conductivity (K) and specific storage (Ss )
      of fractured rocks. Developed methods include kriging, stochastic simulation,
      stochastic inverse modeling, and hydraulic tomography. In this article, I review
      the evolution of various heterogeneity mapping approaches and contend that
      hydraulic tomography, a recently developed aquifer characterization technique for
      unconsolidated deposits, is also a promising approach in yielding robust maps (or
      tomograms) of K and Ss heterogeneity for fractured rocks. While hydraulic
      tomography has recently been shown to be a robust technique, the resolution of
      the K and Ss tomograms mainly depends on the density of pumping and monitoring
      locations and the quality of data. The resolution will be improved through the
      development of new devices for higher density monitoring of pressure responses at
      discrete intervals in boreholes and potentially through the integration of other
      data from single-hole tests, borehole flowmeter profiling, and tracer tests.
      Other data from temperature and geophysical surveys as well as geological
      investigations may improve the accuracy of the maps, but more research is needed.
      Technological advances will undoubtedly lead to more accurate maps. However, more
      effort should go into evaluating these maps so that one can gain more confidence
      in their reliability. 

PMID- 24749937
TI  - Parentification, substance use, and sex among adolescent daughters from ethnic
      minority families: the moderating role of monitoring.
AB  - Guided by structural family systems theory, this study explored the relationship
      between parentification and adolescent daughters' sexual risk engagement and
      substance use. We also explored how adolescent reports of parental monitoring
      moderated the relationship between parentification and adolescent risk. Data were
      from a cross-sectional, cross-generational study of 176 mother-daughter dyads
      from low-income, inner-city, ethnic minority families. In this sample, which
      included a subset of mothers with HIV, parental physical symptoms were associated
      with slightly higher levels of parentification. Parentification was associated
      with adolescent daughters' intention to have sex (but not substance use) in a
      direction opposite to prediction. Higher parentification was associated with
      lower intention to have sex. Parental monitoring did not moderate relationships
      between parentification and adolescent risk. These findings highlight that
      despite the negative influence hypothesized in structural family systems theory,
      parentification was not associated with risk engagement of high-risk adolescent
      daughters in ethnic minority families with low income. 

PMID- 24749940
TI  - The effect of a joint communication campaign on multiple sex partners in
      Mozambique: the role of psychosocial/ideational factors.
AB  - Mozambique is one of the countries in sub-Saharan Africa most affected by the HIV
      epidemic. Multiple and concurrent sexual partnerships (MSP/CP) have been
      recognized as one of the key drivers in the rapid spread of HIV in the region.
      Though HIV prevention programs have been successful in increasing condom use and
      HIV testing, reducing the practice of MSP/CP has been more difficult. Grounding
      their interventions in social and behavior change theory, four organizations in
      Mozambique joined efforts to implement a year-long, multimedia national campaign
      for HIV prevention with emphasis on the reduction of MSP/CP. Evaluating its
      impact and identifying the factors that hinder or contribute to its success are
      critical to building effective programs in the future. With data from a 2011
      population-based survey of 1427 sexually active women and men, multivariate
      causal attribution (MCA) analysis was used to estimate the impact of the campaign
      in the four regions of Mozambique with the highest levels of HIV prevalence. The
      analysis tested the psychosocial pathways through which the campaign was expected
      to affect MSP. The results indicate that exposure (recall) was high; 81.2% of the
      respondents could recall one or more of the communication campaign components.
      The campaign had a significant indirect impact on MSP through its negative effect
      on attitudes that favor MSP, and its positive effect on knowledge and discussion
      of MSP risk with sex partner. This study demonstrates the value of identifying
      appropriate psychosocial factors and using them to design the campaign
      communication strategy, and evaluate the causal pathways by which it has an
      impact. The campaign was successful in changing MSP behavior by working through
      two psychosocial variables.

PMID- 24749943
TI  - Detection of premature ventricular contractions on a ventricular
      electrocardiogram for patients with left ventricular assist devices.
AB  - The ventricular electrocardiogram (v-ECG) was developed for long-term monitoring
      of heartbeats in patients with a left ventricular assist device (LVAD) and does
      not normally have the functionality necessary to detect additional heart
      irregularities that can progress to critical arrhythmias. Although the v-ECG has
      the benefits of physiological optimization and counterpulsation control, when
      abnormal heartbeats occur, the v-ECG does not show the distinct abnormal waveform
      that enables easy detection of an abnormal heartbeat among normal heartbeats on
      the conventional ECG. In this study, the v-ECGs of normal and abnormal heartbeats
      are compared with each other with respect to peak-to-peak voltage, area, and
      maximal slopes, and a new method to detect abnormal heartbeats is suggested. In a
      series of animal experiments with three porcine models (Yorkshire pigs weighing
      30-40 kg), a v-ECG and conventional ECG were taken simultaneously during LVAD
      perfusion. Clinical experts found 104 abnormal heartbeats from the saved
      conventional ECG data and confirmed that the other 3159 heartbeats were normal.
      Almost all of the abnormal heartbeats were premature ventricular contractions
      (PVCs), and there was short-term tachycardia for 3 s. A personal computer was
      used to automatically detect abnormal heartbeats with the v-ECG according to the
      new method, and its results were compared with the clinicians' results. The new
      method found abnormal heartbeats with 90% accuracy, and less than 15% of the
      total PVCs were missed.

PMID- 24749944
TI  - Building polyzwitterion-based multilayers for responsive membranes.
AB  - We systematically investigate the assembly of multilayers based on a
      polyzwitterion (PSBMA) and a polycation (PDADMAC) for the development of ionic
      strength responsive membranes. Although the polyzwitterion is essentially charge
      neutral, we show that specific electrostatic interactions with the PDADMAC allow
      for the formation of stable multilayers. The growth of this LbL system is
      monitored on model surfaces (silica) via optical reflectometry for different pH
      values and ionic strengths. While no effect of pH on the layer growth is
      observed, we did observe a strong dependence on the ionic strength. Upon
      increasing the ionic strength during deposition from 0.005 to 0.5 M NaCl, the
      adsorbed amount is significantly decreased, a behavior that is opposite to
      classical LbL systems. Similar results to those obtained on silica are also
      observed on top of classical LbL systems and on polymeric membranes. This
      demonstrates that the growth of the polyzwitterion multilayers is independent of
      the substrate. Coating these polyzwitterion multilayers on hollow fiber membranes
      via dip-coating yields membranes that are stimuli responsive toward the ionic
      strength of the filtration solution, with an increase in permeability of up to
      108% from 0 to 1.5 M NaCl. We show that the fabrication of the polyzwitterion
      multilayers is an easy and controlled way to provide surfaces, such as membranes,
      with the specific functionalities of polyzwitterions. 

PMID- 24749945
TI  - Sulfur-infiltrated graphene-based layered porous carbon cathodes for high
      performance lithium-sulfur batteries.
AB  - Because of advantages such as excellent electronic conductivity, high theoretical
      specific surface area, and good mechanical flexibility, graphene is receiving
      increasing attention as an additive to improve the conductivity of sulfur
      cathodes in lithium-sulfur (Li-S) batteries. However, graphene is not an
      effective substrate material to confine the polysulfides in cathodes and stable
      the cycling. Here, we designed and synthesized a graphene-based layered porous
      carbon material for the impregnation of sulfur as cathode for Li-S battery. In
      this composite, a thin layer of porous carbon uniformly covers both surfaces of
      the graphene and sulfur is highly dispersed in its pores. The high specific
      surface area and pore volume of the porous carbon layers not only can achieve a
      high sulfur loading in highly dispersed amorphous state, but also can act as
      polysulfide reservoirs to alleviate the shuttle effect. When used as the cathode
      material in Li-S batteries, with the help of the thin porous carbon layers, the
      as-prepared materials demonstrate a better electrochemical performance and cycle
      stability compared with those of graphene/sulfur composites. 

PMID- 24749946
TI  - Evaluation of the content--containing interaction in cosmetic products using gas
      chromatography-mass spectrometry.

PMID- 24749948
TI  - Synthesis of allo- and epi-inositol via the NHC-catalyzed carbocyclization of
      carbohydrate-derived dialdehydes.
AB  - A synthesis of carbocyclic sugars from carbohydrate-derived dialdehydes using
      organocatalysis has been developed. Sorbitol, mannitol, and galactitol were
      converted via 1,6-tritylation, perbenzylation or permethylation, detritylation,
      and Swern oxidation into 2,3,4,5-tetra-O-alkyl-dialdoses that were cyclized via
      the benzoin reaction promoted by a triazolium carbene. Manno- and galacto
      configured dialdehydes gave predominantly single inosose stereoisomers in up to
      75% yield if the mixture was acetylated prior to isolation while the gluco
      dialdehyde afforded a mixture of three stereoisomers in 61% overall yield. The
      inososes were stereospecifically reduced using sodium borohydride and then
      deprotected to give allo- and epi-inositol in good yield that confirmed the
      structural and stereochemical assignments. 

PMID- 24749947
TI  - Innovative personalized medicine in gastric cancer: time to move forward.
AB  - Globally, gastric cancer (GC) is the second leading cancer cause of death. To
      date, only one targeted therapy trial generated positive survival outcomes in a
      selected population among many targeted therapy trials. This trial showed the
      addition of trastuzumab to fluoropyrimidine/platinum chemotherapy as first-line
      chemotherapy for human epidermal growth factor receptor 2 (HER2)-positive GC that
      resulted in an overall survival (OS) benefit. The increasing use of next
      generation sequencing approach to genomically profile GC patients allows the
      identification of many more GC patients who could benefit from specific targeted
      agents. Here we provide a comprehensive review of targeted therapy trials in GC
      and discuss future potential actionable driver mutations in GC. 

PMID- 24749949
TI  - Detection of reactive oxygen species during the cell cycle under normal culture
      conditions using a modified fixed-sample staining method.
AB  - We developed an alternative method of simultaneously monitoring the generation of
      reactive oxygen species (ROS) and cellular oxidative responses using the
      oxidation-sensitive fluorescent probe dichlorofluorescein (DCF) in fixed samples.
      In this study, we evaluated the ability of this method to detect ROS generation
      during the cell cycle under normal culture conditions using flow cytometric
      analyses. Among the fixatives tested, only acetone and paraformaldehyde did not
      alter the endogenous oxidation of the responsive dye 5-(and-6)-chloromethyl-2',7'
      dichlorodihydrofluorescein diacetate (CM-H2DCFDA), which is a chloromethyl
      derivative of H2DCFDA. Only acetone fixation followed by staining with propidium
      iodide was able to detect ROS generation during the cell cycle without altering
      DCF oxidation. Further thymidine treatment led to cell cycle arrest at the G1
      phase followed by the downregulation of total intracellular ROS. Paraformaldehyde
      based fixation enabled the evaluation of ROS generation by immunostaining at a
      different phase of the cell cycle, whereas MPM2 co-staining enabled
      identification of the specific mitotic phase. This study demonstrates a modified
      fixed-sample method that can be used to measure intracellular ROS production
      during the cell cycle using standard immunostaining techniques.

PMID- 24749941
TI  - Role of cues and contexts on drug-seeking behaviour.
AB  - Environmental stimuli are powerful mediators of craving and relapse in substance
      abuse disorders. This review examined how animal models have been used to
      investigate the cognitive mechanisms through which cues are able to affect drug
      seeking behaviour. We address how animal models can describe the way drug
      associated cues come to facilitate the development and persistence of drug
      taking, as well as how these cues are critical to the tendency to relapse that
      characterizes substance-abuse disorders. Drug-associated cues acquire properties
      of conditioned reinforcement, incentive motivation and discriminative control,
      which allow them to influence drug-seeking behaviour. Using these models,
      researchers have been able to investigate the pharmacology subserving the
      behavioural impact of environmental stimuli, some of which we highlight.
      Subsequently, we examine whether the impact of drug-associated stimuli can be
      attenuated via a process of extinction, and how this question is addressed in the
      laboratory. We discuss how preclinical research has been translated into
      behavioural therapies targeting substance abuse, as well as highlight potential
      developments to therapies that might produce more enduring changes in behaviour.

PMID- 24749950
TI  - Military-related posttraumatic stress disorder and intimate relationship
      behaviors: a developing dyadic relationship model.
AB  - The protracted conflict in Iraq and Afghanistan and an all-volunteer military has
      resulted in multiple war zone deployments for many service members. While quick
      redeployment turnaround has left little time for readjustment for either the
      service member or family, dealing with the long-term sequelae of combat exposure
      often leaves families and intimate partners ill-prepared for years after
      deployments. Using a modified grounded theory approach, digitally recorded couple
      interviews of 23 couples were purposefully selected from a larger sample of 441
      couples to better understand the impact of war zone deployment on the couple. The
      veteran sample was recruited from a randomly selected cohort of men in treatment
      for posttraumatic stress disorder (PTSD). Overall, it was found when veterans
      experiencing deployment-related PTSD reenter or start new intimate relationships
      they may bring with them a unique cluster of interrelated issues which include
      PTSD symptoms, physical impairment, high rates of alcohol and/or drug abuse, and
      psychological and physical aggression. These factors contributed to a dynamic of
      exacerbating conflict. How these couples approached relationship qualities of
      mutuality, balanced locus of control and weakness tolerance across six axes of
      caregiving, disability, responsibility, trauma, communication, and community
      impacted the couple's capacity to communicate and resolve conflict. This dyadic
      relationship model is used to help inform implications for clinical practice. 

PMID- 24749951
TI  - Polyhydroxy cyclohexanols from a Dendrodochium sp. fungus associated with the sea
      cucumber Holothuria nobilis Selenka.
AB  - Four cyclohexanol analogues, dendrodochols A-D (1-4), were isolated from a
      Dendrodochium sp. fungus associated with the sea cucumber Holothuria nobilis
      Selenka collected from the South China Sea. The structures were elucidated by
      means of detailed spectroscopic analysis. The absolute configurations were
      assigned using a solution TDDFT/ECD calculation approach and the modified
      Mosher's method. In an in vitro bioassay, these compounds exhibited no growth
      inhibition activity against the A549 and MG63 cell lines. Dendrodochols 1 and 3
      exhibited modest antifungal activity against Candida strains, Cryptococcus
      neoformans, and Trichophyton rubrum, whereas 2 and 4 showed no activity against
      the tested strains. 

PMID- 24749952
TI  - Nanoporous membranes with tunable pore size by pressing/sintering silica
      colloidal spheres.
AB  - We prepared robust nanoporous membranes with controlled area and uniform
      thickness by pressing silica colloidal spheres into disks followed by sintering.
      Three different diameters of silica particles, 390, 220, and 70 nm, were used to
      prepare the membranes with different pore size. In order to evaluate their size
      selectivity, we measured the diffusion of polystyrene particles through these
      membranes. Although pressed silica colloidal membranes do not possess visible
      order or uniform pore size, they showed size-selective transport. We also
      demonstrated that pressed silica colloidal membranes can be functionalized via
      pore-filling. Sulfonated polymer brushes were grown inside the pores via surface
      initiated atom transfer radical polymerization, which resulted in a material with
      high proton conductivity suitable for fuel cell applications. 

PMID- 24749953
TI  - Strawberry extract presents antiplatelet activity by inhibition of inflammatory
      mediator of atherosclerosis (sP-selectin, sCD40L, RANTES, and IL-1beta) and
      thrombus formation.
AB  - Cardiovascular disease prevention is of high priority in developed countries.
      Healthy eating habits including the regular intake of an antithrombotic diet
      (fruit and vegetables) may contribute to prevention. Platelet function is a
      critical factor in arterial thrombosis and the effect strawberries have is still
      unclear. Therefore, the aim of this study was to systematically examine the
      action of strawberries in preventing platelet activation and thrombus formation.
      Strawberry extract concentration-dependently (0.1-1 mg/ml) inhibited platelet
      aggregation induced by ADP and arachidonic acid. At the same concentrations as
      strawberry inhibits platelet aggregation, it significantly decreased sP-selectin,
      sCD40L, RANTES, and IL-1beta levels. The strawberry may exert significant
      protective effects on thromboembolic-related disorders by inhibiting platelet
      aggregation. Also, this suggests that antithrombotic activity may have novel anti
      inflammatory effects. 

PMID- 24749954
TI  - Seasonal and spatial variations in microbial activity at various phylogenetic
      resolutions at a groundwater - surface water interface.
AB  - We investigated the seasonal and spatial variation in activity and density of the
      metabolically active in situ microbial community (AIMC) at a landfill leachate
      impacted groundwater - surface water interface (GSI). A series of AIMC traps were
      designed and implemented for AIMC sampling and microbial activity and density
      examinations. Measurements were made not only at the level of bacterial domain
      but also at the levels of alphaproteobacterial Rhizobiales order and
      gammaproteobacterial Pseudomonas genus, both of which included a large number of
      iron-oxidizing bacteria as revealed from previous analysis. Consistently higher
      microbial activities with less variation in depth were measured in the AIMC traps
      than in the ambient sediments. Flood disturbance appeared to control AIMC
      activity distributions at the gradually elevated GSI. The highest AIMC activities
      were generally obtained from locations closest to the free surface water boundary
      except during the dry season when microbial activities were similar across the
      entire GSI. A clone library of AIMC 16S rRNA genes was constructed, and it
      confirmed the predominant role of the targeted alphaproteobacterial group in AIMC
      activity and composition. This taxon constituted 2%-14% of all bacteria with
      similar activity distribution profiles. The Pseudomonas group occupied only
      0.10/00-0.50/00 of the total bacterial density, but its activity was 27 times
      higher than the bacterial average. Of the 16S rRNA sequences in the AIMC clone
      library, 7.5% were phylogenetically related to putative IOB, supporting the
      occurrence and persistence of active microbial iron oxidation across the studied
      iron-rich GSI ecosystem. 

PMID- 24749955
TI  - Characterizing fluorotelomer and polyfluoroalkyl substances in new and aged
      fluorotelomer-based polymers for degradation studies with GC/MS and LC/MS/MS.
AB  - Fluorotelomer-based polymers (FTPs), the dominant product of the fluorotelomer
      industry, are antistaining and antiwetting agents that permeate the products and
      surfaces of modern society. However, the degree to which these materials expose
      humans and the environment to fluorotelomer and perfluorinated compounds,
      including recalcitrant and toxic compounds such as perfluorooctanoic acid (PFOA),
      is ill-defined. The design intent of FTPs, to minimize interaction with other
      substances, including solvents, heretofore has stymied efforts to develop robust
      methods to characterize the content of monomers and associated compounds of new
      commercial FTPs, as well as commercial FTPs that have been aged in environmental
      media for degradation testing. Here we show that FTPs can be exhausted of these
      compounds and quantitated by (i) drying the FTP on a suitable substrate at
      elevated temperature to achieve low, constant monomer concentrations; (ii) serial
      extraction with MTBE for fluorotelomer-monomer analysis by GC/MS in PCI mode;
      followed by (iii) serial extraction with 90/10 ACN/H2O for polyfluorocompound
      analysis by LC/MS/MS in negative ESI mode. This approach yields exhaustive,
      internally consistent accounting of monomers and associated compounds for FTPs,
      either alone or in a soil matrix (representing an environmental medium), for both
      new and simulated-aged FTPs to allow degradation testing, and for fluorinated
      compounds at least as long as C12. 

PMID- 24749956
TI  - The use of a nasogastric tube to facilitate nasotracheal intubation: a randomised
      controlled trial.
AB  - During nasotracheal intubation, the tracheal tube passes through either the upper
      or lower pathway in the nasal cavity, and it has been reported to be safer that
      the tracheal tube passes though the lower pathway, just below the inferior
      turbinate. We evaluated the use of a nasogastric tube as a guide to facilitate
      tracheal tube passage through the lower pathway, compared with the 'conventional'
      technique (blind insertion of the tracheal tube into the nasal cavity). A total
      of 60 adult patients undergoing oral and maxillofacial surgery were included in
      the study. In 20 out of 30 patients (66.7%) with the nasogastric tube-guided
      technique, the tracheal tube passed through the lower pathway, compared with 8
      out of 30 patients (26.7%) with the 'conventional' technique (p = 0.004). Use of
      the nasogastric tube-guided technique reduced the incidence and severity of
      epistaxis (p = 0.027), improved navigability (p = 0.034) and required fewer
      manipulations (p = 0.001) than the 'conventional' technique.

PMID- 24749957
TI  - Facile photochemical synthesis of 5,10-disubstituted [5]helicenes by removing
      molecular orbital degeneracy.
AB  - Photocyclodehydrogenation is a key reaction to synthesize helicenes; however,
      because of overannulation, it is not applicable to the synthesis of [5]helicene.
      Introduction of a cyano group was found to remove the orbital degeneracy of the
      low-lying unoccupied MOs; consequently, the lowest excitation comprises a single
      transition involving the C2-antisymmetric MO. Therefore, the problematic
      overannulation can be effectively suppressed. Moreover, in combination with the
      Knoevenagel reaction, a one-pot synthesis of 5,10-dicyano[5]helicene with 67%
      yield was accomplished. 

PMID- 24749960
TI  - An updated feminist view of intimate partner violence.
AB  - In this article, we explore intimate partner violence (IPV) from an
      intersectional, feminist perspective. We describe how an updated feminist view
      guides us to a perspective on IPV that is more strongly grounded in an
      antioppressive, nonviolent, socially just feminist stance than a second-wave
      gender-essential feminist stance that suggests that patriarchy is the cause of
      IPV. At the time we began to work together it seemed that a researcher had to be
      identified as a "family violence" researcher or a "feminist" researcher of
      violence against women, and that it wasn't possible to be a feminist researcher
      who looked beyond patriarchy as the cause of IPV. We advocate critically thinking
      about essentialist practices in clinical work so that we can maintain an
      antioppressive, socially just, nonviolent approach to working with clients who
      experience IPV. 

PMID- 24749959
TI  - Olmesartan prevents cardiac rupture in mice with myocardial infarction by
      modulating growth differentiation factor 15 and p53.
AB  - BACKGROUND AND PURPOSE: Cardiac rupture is a catastrophic complication that
      occurs after acute myocardial infarction (MI) and, at present, there are no
      effective pharmacological strategies for preventing this condition. Here we
      investigated the effect of the angiotensin II receptor blocker olmesartan (Olm)
      on post-infarct cardiac rupture and its underlying mechanisms of action.
      EXPERIMENTAL APPROACH: C57Bl/6 mice with MI were treated with Olm, aldosterone
      (Aldo) or vehicle. Cultured neonatal cardiomyocytes and fibroblasts were exposed
      to normoxia or anoxia and treated with angiotensin II (Ang II), RNH6270 (active
      ingredient of Olm) or Aldo. KEY RESULTS: The mortality rate and incidence of
      cardiac rupture in MI mice during the first week in the Olm-treated group were
      significantly lower than in the vehicle-treated group. Olm or RNH6270 reduced
      myeloperoxidase staining in the infarcted myocardium, decreased apoptosis in
      cultured cardiomyocytes and fibroblasts, as assessed by Hoechst staining and
      TUNEL assay, attenuated the accumulation of p53 and phosphorylated p53 and
      cleaved caspase 3 induced by MI or Ang II, as assessed by Western blotting, and
      up-regulated growth differentiation factor-15 (GDF-15). In cultured
      cardiomyocytes and fibroblasts, treatment with Ang II, Aldo or anoxia
      significantly down-regulated the expression of GDF-15. CONCLUSIONS AND
      IMPLICATIONS: Olm prevents cardiac rupture through inhibition of apoptosis and
      inflammation, which is attributable to the down-regulation of p53 activity and up
      regulation of GDF-15. Our findings suggest that early administration of an AT1
      receptor anatagonist to patients with acute MI is a potential preventive approach
      for cardiac rupture.

PMID- 24749961
TI  - Tracking eye movements to localize Stroop interference in naming: word planning
      versus articulatory buffering.
AB  - Investigators have found no agreement on the functional locus of Stroop
      interference in vocal naming. Whereas it has long been assumed that the
      interference arises during spoken word planning, more recently some investigators
      have revived an account from the 1960s and 1970s holding that the interference
      occurs in an articulatory buffer after word planning. Here, 2 color-word Stroop
      experiments are reported that tested between these accounts using eye tracking.
      Previous research has indicated that the shifting of eye gaze from a stimulus to
      another occurs before the articulatory buffer is reached in spoken word planning.
      In the present experiments, participants were presented with color-word Stroop
      stimuli and left- or right-pointing arrows on different sides of a computer
      screen. They named the color attribute and shifted their gaze to the arrow to
      manually indicate its direction. If Stroop interference arises in the
      articulatory buffer, the interference should be present in the color-naming
      latencies but not in the gaze shift and manual response latencies. Contrary to
      these predictions, Stroop interference was present in all 3 behavioral measures.
      These results indicate that Stroop interference arises during spoken word
      planning rather than in articulatory buffering.

PMID- 24749962
TI  - Incidental learning and task boundaries.
AB  - For skill learning processes to be effective, they must encode associations that
      are inherent to the current task and avoid those that are spurious or particular
      to training conditions so that learning can transfer to novel situations. Some
      everyday contexts even require grouped responding to simultaneously presented
      stimuli. Here we test whether learning of these grouped responses depends on
      overlap in stimulus and/or response modality or on the conceptualization of the
      stimulus and response streams as belonging to a common task. In the present
      experiments, participants made 2 responses to 2 simultaneously presented stimuli,
      and learning was assessed by comparing performance on response combinations that
      had been practiced throughout training to performance on combinations that had
      been withheld. Experiments 1-4 paired the same visual-manual task with a 2nd task
      that differed in terms of the stimulus modality, the response modality, neither
      modality, or both modalities. Combination-specific learning was only observed
      when both the stimulus and response modalities were the same for the 2 tasks.
      However, Experiments 5 and 6 showed that combination-specific learning could
      occur with nonoverlapping stimulus modalities or response modalities if the 2
      tasks were conceptually related. The results suggest that task representations
      provide top-down constraints on skill learning processes.

PMID- 24749963
TI  - An exemplar-familiarity model predicts short-term and long-term probe recognition
      across diverse forms of memory search.
AB  - Experiments were conducted to test a modern exemplar-familiarity model on its
      ability to account for both short-term and long-term probe recognition within the
      same memory-search paradigm. Also, making connections to the literature on
      attention and visual search, the model was used to interpret differences in probe
      recognition performance across diverse conditions that manipulated relations
      between targets and foils across trials. Subjects saw lists of from 1 to 16 items
      followed by a single item recognition probe. In a varied-mapping condition,
      targets and foils could switch roles across trials; in a consistent-mapping
      condition, targets and foils never switched roles; and in an all-new condition,
      on each trial a completely new set of items formed the memory set. In the varied
      mapping and all-new conditions, mean correct response times (RTs) and error
      proportions were curvilinear increasing functions of memory set size, with the RT
      results closely resembling ones from hybrid visual-memory search experiments
      reported by Wolfe (2012). In the consistent-mapping condition, new-probe RTs were
      invariant with set size, whereas old-probe RTs increased slightly with increasing
      study-test lag. With appropriate choice of psychologically interpretable free
      parameters, the model accounted well for the complete set of results. The work
      provides support for the hypothesis that a common set of processes involving
      exemplar-based familiarity may govern long-term and short-term probe recognition
      across wide varieties of memory- search conditions.

PMID- 24749964
TI  - The role of consonant/vowel organization in perceptual discrimination.
AB  - According to a recent hypothesis, the CV pattern (i.e., the arrangement of
      consonant and vowel letters) constrains the mental representation of letter
      strings, with each vowel or vowel cluster being the core of a unit. Six
      experiments with the same/different task were conducted to test whether this
      structure is extracted prelexically. In the mismatching trials, the targets were
      pseudowords built by the transposition of 2 adjacent letters from base words. In
      one condition, the pseudowords had the same number of vowel clusters as the base
      word, whereas in another condition, the transposition modified the number of
      vowel clusters (e.g., poirver: 2 vowel clusters vs. povirer: 3 vowel clusters,
      from POIVRER: 2 vowel clusters). In Experiment 1, pseudowords with a different
      number of vowel clusters were more quickly processed than pseudowords preserving
      the CV structure of their base word. Experiment 2 further showed that this effect
      was not due to changes in syllabic structure. In Experiment 3, the pattern of
      results was also replicated when the category (consonant or vowel) of the
      transposed letters was strictly equated between conditions. Experiments 4 and 5
      confirmed that the effects were not attributable to lexical processing, to
      differences in letter identity, or to the position of transpositions. The results
      suggest that the orthographic representation of letter strings is influenced by
      the CV pattern at an early, prelexical processing stage.

PMID- 24749965
TI  - Sample size bias in judgments of perceptual averages.
AB  - Previous research has shown that people exhibit a sample size bias when judging
      the average of a set of stimuli on a single dimension. The more stimuli there are
      in the set, the greater people judge the average to be. This effect has been
      demonstrated reliably for judgments of the average likelihood that groups of
      people will experience negative, positive, and neutral events (Price, 2001;
      Price, Smith, & Lench, 2006) and also for estimates of the mean of sets of
      numbers (Smith & Price, 2010). The present research focuses on whether this
      effect is observed for judgments of average on a perceptual dimension. In 5
      experiments we show that people's judgments of the average size of the squares in
      a set increase as the number of squares in the set increases. This effect occurs
      regardless of whether the squares in each set are presented simultaneously or
      sequentially; whether the squares in each set are different sizes or all the same
      size; and whether the response is a rating of size, an estimate of area, or a
      comparative judgment. These results are consistent with a priming account of the
      sample size bias, in which the sample size activates a representation of
      magnitude that directly biases the judgment of average.

PMID- 24749966
TI  - Give your ideas some legs: the positive effect of walking on creative thinking.
AB  - Four experiments demonstrate that walking boosts creative ideation in real time
      and shortly after. In Experiment 1, while seated and then when walking on a
      treadmill, adults completed Guilford's alternate uses (GAU) test of creative
      divergent thinking and the compound remote associates (CRA) test of convergent
      thinking. Walking increased 81% of participants' creativity on the GAU, but only
      increased 23% of participants' scores for the CRA. In Experiment 2, participants
      completed the GAU when seated and then walking, when walking and then seated, or
      when seated twice. Again, walking led to higher GAU scores. Moreover, when seated
      after walking, participants exhibited a residual creative boost. Experiment 3
      generalized the prior effects to outdoor walking. Experiment 4 tested the effect
      of walking on creative analogy generation. Participants sat inside, walked on a
      treadmill inside, walked outside, or were rolled outside in a wheelchair. Walking
      outside produced the most novel and highest quality analogies. The effects of
      outdoor stimulation and walking were separable. Walking opens up the free flow of
      ideas, and it is a simple and robust solution to the goals of increasing
      creativity and increasing physical activity.

PMID- 24749968
TI  - Authors' reply.

PMID- 24749969
TI  - Aqueous dispersions of organogel nanoparticles - potential systems for cosmetic
      and dermo-cosmetic applications.
AB  - OBJECTIVE: The preparation and physicochemical characterization of organogel
      nanoparticles dispersed in water have been developed. These systems could be
      employed as nanocarrier for cosmetic applications or as hydrophobic reservoirs
      for drug delivery. METHODS: Gelled particles of organic liquid and 12
      hydroxystearic acid (organogelator) were obtained by hot emulsification (T>Tgel),
      with a surfactant (acetylated glycol stearate) and polymers (sodium hyaluronate
      and polyvinyl alcohol) as stabilizing agents, and cooling at room temperature
      (T<Tgel). An organic UVB sunscreen molecule, obtained by microwave activation,
      was used as a hydrophobic model molecule. The physicochemical properties of the
      starting organogel (gelation tests; rheological study) and the dispersed gelled
      particles (rheological study; particle mean size, size distribution, zeta
      potential measurements; physical stability evaluation; UVB absorption and water
      resistance ability) were studied. The synthesis of sunscreen compound using
      microwave activation was also described. RESULTS: According to the gelation test
      results, organogels were obtained with various organic liquids. Vaseline and
      almond oils were selected as organic medium for the gelled nanoparticle
      preparation. A preliminary formulation study was carried out in order to
      determine the optimal experimental conditions to obtain stable nanoparticle
      dispersions. Gelled nanoparticles contained the sunscreen model molecule, with
      mean size of 450 nm, polydispersity index of 0.18 and zeta-potential value above 
      30 mV, were obtained by ultrasound probe homogenization method. A comparative
      study of their dispersion ageing showed a greatly enhanced stability after
      gelation. According to the UVB absorption evaluation, gelled particles improved
      the photoprotective ability and the photostability of immobilized UVB blocker.
      They showed a high water resistance (~83%) even after 40 min of immersion.
      CONCLUSION: The obtained results demonstrate the interest of these gelled
      nanoparticles and their aqueous dispersion for the preparation of new
      formulations for cosmetic and dermo-cosmetic applications.

PMID- 24749970
TI  - Evaluating ex vivo fluorescence confocal microscopy images of basal cell
      carcinomas in Mohs excised tissue.
AB  - BACKGROUND: Fluorescence confocal microscopy (FCM) is an emerging technology for
      rapid imaging of excised tissue, without the need for frozen- or fixed-section
      processing. Basal cell carcinomas (BCCs) can be detected in Mohs excisions
      although few studies have described the major BCC findings as seen on FCM.
      OBJECTIVES: To describe the major BCC findings of excised tissue during Mohs
      surgery and to correlate them with histopathology. METHODS: Freshly excised
      tumours and frozen-thawed discarded tissue of BCC during Mohs surgery were
      analysed by means of FCM. A side-by-side correlation between FCM images and
      histological sections was performed. The FCM features of overlying skin and
      adnexal structures were also described. RESULTS: Sixty-four BCC cases were
      analysed. Distinct BCC types appeared unique in terms of shape and size of tumour
      islands [bigger in nodular (18/25), smaller and rounded in micronodular (7/7) and
      tiny cords for infiltrative ones (24/30)] and for the presence of clefting,
      palisading and increased nucleus/cytoplasm ratio. An excellent correlation was
      found between FCM and histological findings (Cohen's kappa statistics = 0.9). In
      six cases, the presence of sebaceous glands and intense stroma reaction
      represented possible confounders. CONCLUSIONS: Fluorescence confocal microscopy
      is a fast and new imaging technique that allows an excellent visualization of
      skin structures and BCC findings during Mohs surgery.

PMID- 24749971
TI  - Young adult romantic couples' conflict resolution and satisfaction varies with
      partner's attention-deficit/hyperactivity disorder type.
AB  - Attention-deficit/hyperactivity disorder (ADHD) has previously been associated
      with less satisfaction and success in romantic relationships. This study compares
      conflict resolution and problem-solving behaviors in young adult romantic couples
      either having one partner with ADHD combined type (C-couples), having one partner
      identified with ADHD inattentive type (IA-couples), or in which neither partner
      has an ADHD diagnosis (nondiagnosed [ND] couples). Self-reports of current and
      childhood ADHD symptoms corroborated diagnostic status and speaker and listener
      behaviors, coded via the Rapid Couples Interaction Scoring System (Gottman,
      1996), were the primary dependent variables. Analyses revealed greater negativity
      and less positivity in C-couples' behavior during a conflict resolution task,
      relative to IA and ND couples, and this corresponded with couples' relational
      satisfaction. IA-couples emitted relational behavior that was largely similar to
      ND couples. Findings support that relational impairment exists in C-couples, and
      to some degree, contrast with previous research suggesting that individuals with
      predominant inattention experience greater social impairment in adulthood than
      those with other types of ADHD. 

PMID- 24749972
TI  - Highly stretchable and sensitive strain sensor based on silver nanowire-elastomer
      nanocomposite.
AB  - The demand for flexible and wearable electronic devices is increasing due to
      their facile interaction with human body. Flexible, stretchable and wearable
      sensors can be easily mounted on clothing or directly attached onto the body.
      Especially, highly stretchable and sensitive strain sensors are needed for the
      human motion detection. Here, we report highly flexible, stretchable and
      sensitive strain sensors based on the nanocomposite of silver nanowire (AgNW)
      network and PDMS elastomer in the form of the sandwich structure (i.e., AgNW thin
      film embedded between two layers of PDMS). The AgNW network-elastomer
      nanocomposite based strain sensors show strong piezoresistivity with tunable
      gauge factors in the ranges of 2 to 14 and a high stretchability up to 70%. We
      demonstrate the applicability of our high performance strain sensors by
      fabricating a glove integrated with five strain sensors for the motion detection
      of fingers and control of an avatar in the virtual environment. 

PMID- 24749973
TI  - The importance of genetic susceptibility in Dupuytren's disease.
AB  - Dupuytren's disease (DD) is a progressive fibromatosis that causes the formation
      of nodules and cords in the palmar aponeurosis leading to flexion contracture of
      affected fingers. The etiopathogenesis is multifactorial with a strong genetic
      predisposition. It is the most frequent genetic disorder of connective tissues.
      We have collected clinical data from 736 unrelated individuals with DD who
      underwent surgical treatment from Germany and Switzerland. We evaluated a
      standardised questionnaire, assessed the importance of different risk factors and
      compared subgroups with and without positive family history. We found that family
      history clearly had the strongest influence on the age at first surgery compared
      to environmental factors, followed by male sex. Participants with a positive
      family history were on average 55.9 years of age at the first surgical
      intervention, 5.2 years younger than probands without known family history (p =
      6.7 * 10(-8) ). The percentage of familial cases decreased with age of onset from
      55% in the 40-49 years old to 17% at age 80 years or older. Further risk factors
      analysed were cigarettes, alcohol, diabetes, hypertension, and epilepsy. Our data
      pinpoint the importance of genetic susceptibility for DD, which has long been
      underestimated. 

PMID- 24749974
TI  - Confinement of ferroelectric domain-wall motion at artificially formed conducting
      nanofilaments in epitaxial BiFeO3 thin films.
AB  - We report confinement of ferroelectric domain-wall motion at conducting
      nanofilament wall in epitaxial BiFeO3 thin film on Nb-doped SrTiO3 substrate. The
      BiFeO3 film exhibited well-defined ferroelectric response and unipolar resistive
      switching behavior. We artificially formed conducting-nanofilaments in the BiFeO3
      via conducting atomic force microscope techniques. The conducting-nanofilament
      wall, which does not possess any ferroelectric polarization, is then able to
      block domain propagation. Consequently, we demonstrate that the domain-wall
      motion is effectively confined within the conducting-nanofilament wall during
      polarization switching. This significant new insight potentially gives an
      opportunity for the artificial manipulation of nanoscale ferroelectric domain. 

PMID- 24749975
TI  - The heart of genetic testing.

PMID- 24749976
TI  - Dose-ranging study of the performance of the natural oxygen transporter HEMO2
      Life in organ preservation.
AB  - The intensity of ischemia-reperfusion injury of the donor organ during the
      preservation phase and after anastomosis is acknowledged as being a key factor
      for long-term graft outcome. We previously showed that the addition of 5 g/L of
      the natural oxygen carrier HEMO2 Life was beneficial for the cold static
      preservation of kidney grafts in both University of Wisconsin (UW) and histidine
      tryptophan-ketoglutarate solutions. Herein, we refined these findings by
      evaluating HEMO2 Life at various dose levels in UW, both in vitro with
      endothelial cells and in vivo in a pig kidney autotransplantation preclinical
      model. We showed in vitro that cells were significantly better preserved with
      HEMO2 Life in a dose-dependent manner, with benefits in terms of survival,
      metabolic activity, and cellular integrity. In vivo, serum creatinine
      measurements at reperfusion confirmed the important benefits of HEMO2 Life
      treatment on function recovery at the dose levels of 1, 2, and 5 g/L. Likewise,
      histological analysis of kidney parenchyma biopsies from day 7 confirmed the
      superiority of HEMO2 Life-supplemented UW over UW alone, and there was no
      difference between the doses. Three months' follow-up confirmed the trend of the
      first 2 weeks, with creatinine and fibrosis levels similar to those in
      pretransplant kidneys. 

PMID- 24749977
TI  - The complete mitochondrial genome of the Kinmen's population of endangered minnow
      Metzia mesembrinum (Cypriniformes, Cyprinidae) from Taiwan.
AB  - Here we describe the complete mitochondrial genome sequence of endangered minnow,
      Metzia mesembrinum, which collected from Kimnen island, Fujian Province of
      Taiwan. The circular mitogenome (16,603 bp) consists of 13 protein coding, 22
      tRNA, 2 rRNA genes and 1 control region. It has the typical vertebrate
      mitochondrial gene arrangement. The overall base composition in descending order
      is A (32.0%), T (27.1%), C (25.2%), G (15.7%) with rather higher AT content as
      59.1%. Yuan et al. reported the complete mitogenome (KF997093) of M. mesembrimum
      from southern China that may belong to other congeneric species, but not exactly
      M. mesembrinum collected from either southern Fujian or Taiwan. The well
      identified species sequence data of Metzia mesembrinum would be rather beneficial
      for further phlyogenetic approach for congeneric species in East and Southeast
      Asia.

PMID- 24749978
TI  - The complete mitochondrial genome of small sliver gugeon Squalidus gracilis
      (Teleostei, Cyprinidae).
AB  - In this study, the complete mitogenome sequence of small silver gugeon Squalidus
      gracilis has been amplified. The mitogenome, consisting of 16,605 base pairs
      (bp), had the typical vertebrate mitochondrial gene arrangement, including 13
      protein-coding genes, 22 transfer RNAs, 2 ribosomal RNAs genes and a non-coding
      control region (CR). CR of 928 bp length is located between tRNA(Pro) and
      tRNA(Phe). The overall base composition of S. gracilis is 29.8% for A, 27.6% for
      C, 25.7% for T and 16.9% for G, with higher AT content of 55.5%. The complete
      mitogenome may provide rather essential and important DNA molecular data for
      further phylogenetic analysis for not only congeneric species but also higher
      different taxa of Cyprinid fishes.

PMID- 24749979
TI  - The complete mitochondrial genome of spotted hidden-teeth goby Apocryptodon
      punctatus Tomiyama (Perciformes, Gobiidae).
AB  - The complete mitochondrial genome of the oxudercine, spotted hidden-teeth goby
      Apocryptodon punctatus (Tomiyama, 1934) has been amplified in this study.
      Apocryptodon punctatus was found in Japan, Taiwan and Eastern Mainland China. The
      complete mitochondrial genome is 16,567 base pairs (bp) in total length, had the
      typical vertebrate mitochondrial gene arrangement, including 13 protein-coding
      genes, 2 rRNAs, 22 tRNAs, 1 control region (CR) and 1 light-strand replication
      origin (OL). The overall base composition of Apocryptodon punctatus is 29.2% for
      A, 28.6% for T, 25.9% for C, 16.3% for G, with higher AT content 57.8%. This
      study will contribute and be rather beneficial for understanding the phylogenetic
      approach of species of Apocryptodon and the related genera among gobioids. 

PMID- 24749980
TI  - Development of a fluorometric microplate antiadhesion assay using uropathogenic
      Escherichia coli and human uroepithelial cells.
AB  - A fluorometric microplate assay has been developed to determine Escherichia (E.)
      coli adhesion to uroepithelial cells (UEC). P-fimbriated E. coli were labeled
      with BacLight Green and preincubated 30 min with human urine or standard.
      Fluorescent-E. coli were added to UEC in mircoplates at a 400:1 ratio, incubated
      1 h, and washed, and the fluorescence intensity was measured. Specific labeling
      and adherence were confirmed by flow cytometry. A myricetin (1) standard curve (0
      30 MUg/mL) was developed; the lower limit of detection was 0.1 MUg/mL, and half
      maximal inhibitory concentration was 0.88 MUg/mL (intra- and interassay
      coefficients of variance were <10% and <15%, respectively). Vaccinium macrocarpon
      (cranberry) extracts, quercetin (2), and procyanidins B1 (3), B2 (4), and C1 (5)
      showed similar inhibition. Antiadhesion activity of urine samples from subjects
      (n = 12) consuming placebo or V. macrocarpon beverage determined using this assay
      was positively correlated (R(2) = 0.78; p < 0.01) with a radiolabeled-E. coli
      assay. 

PMID- 24749981
TI  - Iron-catalyzed synthesis of thioesters from thiols and aldehydes in water.
AB  - The preparation of thioesters through the iron-catalyzed coupling reaction of
      thiols with aldehydes is described. The reactions were carried out by using tert
      butyl hydroperoxide (TBHP) as an oxidant and water as a solvent in most cases.
      This system is compatible with a variety of functional groups. 

PMID- 24749983
TI  - Using online computer tailoring to promote physical activity: a randomized trial
      of text, video, and combined intervention delivery modes.
AB  - Website-delivered interventions are increasingly used to deliver physical
      activity interventions, yet problems with engagement and retention result in
      reduced effectiveness. Hence, alternative modes of online intervention delivery
      need to be explored. Therefore, this study aimed to evaluate the acceptability
      and effectiveness of a computer-tailored physical activity intervention delivered
      on the Internet in 3 delivery modes: video, text, or both. Australian adults (N =
      803), recruited through e-mail, were randomized into the three delivery modes and
      received personal physical activity advice. Intervention content was identical
      across groups. Repeated measures analyses of variance were used to compare the
      three groups regarding acceptability, website usability, and physical activity.
      Participants in the video group accepted the content of the physical activity
      advice significantly better (F = 5.59; p < .01), and spent significantly more
      time on the website (F = 21.19; p < .001) compared with the text and combination
      groups. Total physical activity improved significantly over time in all groups (F
      = 3.95; p < .01). Although the combination group increased physical activity the
      most, few significant differences between groups were observed. Providing video
      tailored feedback has advantages over the conventional text-tailored
      interventions; however, this study revealed few behavioral differences. More
      studies, examining alternative delivery modes, that can overcome the limitations
      of the present study, are needed.

PMID- 24749982
TI  - Serine proteases and protease-activated receptor 2 mediate the proinflammatory
      and algesic actions of diverse stimulants.
AB  - BACKGROUND AND PURPOSE: Although serine proteases and agonists of protease
      activated receptor 2 (PAR2) cause inflammation and pain, the spectrum of
      proteases that are activated by proinflammatory and algesic stimuli and their
      contribution to inflammatory pain are uncertain. EXPERIMENTAL APPROACH: Enzymic
      assays and selective inhibitors were used to characterize protease activity in
      mice after intraplantar injections of formalin, bradykinin, PAR2 activating
      peptide (AP) or vehicle. The capacity of these proteases and of recombinant mouse
      trypsin 4 to cleave fragments of PAR2 and to activate PAR2 in cell lines was
      determined. Protease inhibitors and par2 (-/-) mice were used to assess the
      contributions of proteases and PAR2 to pain and inflammation. KEY RESULTS:
      Intraplantar injection of formalin, bradykinin or PAR2-AP led to the activation
      of proteases that were susceptible to the serine protease inhibitor melagatran
      but resistant to soybean trypsin inhibitor (SBTI). Melagatran inhibited mouse
      trypsin 4, which degraded SBTI. Proteases generated in inflamed tissues cleaved
      PAR2-derived peptides. These proteases and trypsin 4 increased [Ca(2+) ]i in PAR2
      transfected but not in untransfected cells, and melagatran suppressed this
      activity. Melagatran or PAR2 deletion suppressed oedema and mechanical
      hypersensitivity induced by intraplantar formalin, bradykinin and PAR2-AP, but
      had no effect on capsaicin-induced pain. CONCLUSIONS AND IMPLICATIONS: Diverse
      proinflammatory and algesic agents activate melagatran-sensitive serine proteases
      that cause inflammation and pain by a PAR2-mediated mechanism. By inducing self
      activating proteases, PAR2 amplifies and sustains inflammation and pain. Serine
      protease inhibitors can attenuate the inflammatory and algesic effects of diverse
      stimuli, representing a useful therapeutic strategy.

PMID- 24749984
TI  - Peroxiredoxin is a versatile self-assembling tecton for protein nanotechnology.
AB  - The potential for protein tectons to be used in nanotechnology is increasingly
      recognized, but the repertoire of stable proteins that assemble into defined
      shapes in response to an environmental trigger is limited. Peroxiredoxins (Prxs)
      are a protein family that shows an amazing array of supramolecular assemblies,
      making them attractive tectons. Human Prx3 (hPrx3) forms toroidal oligomers
      characteristic of the Prx family, but no structure has been solved to date. Here
      we report the first 3-D structure of this protein, derived from single-particle
      analysis of TEM images, establishing a dodecameric structure. This result was
      supported by SAXS measurements. We also present the first detailed structure of a
      double toroidal Prx from a higher organism determined by SPA. Guided by these
      structures, variants of the protein were designed to facilitate controlled
      assembly of protein nanostructures through the association of the toroids. We
      observed an enhanced population of stacked toroids, as seen by TEM; nanocages and
      interlocked toroids were also visible. Low pH was successfully predicted to
      generate long ordered nanotubes. Control over the length of the tubes was gained
      by adding ammonium sulfate to the assembly buffer. These versatile assembly
      properties demonstrate the considerable potential of hPrx3 as a tecton for
      protein nanotechnology. 

PMID- 24749985
TI  - Bistable multifunctionality and switchable strong ferromagnetic-to
      antiferromagnetic coupling in a one-dimensional rhodium(I)-semiquinonato complex.
AB  - We present a comprehensive study of the synthesis, heat capacity, crystal
      structures, UV-vis-NIR and mid-IR spectra, DFT calculations, and magnetic and
      electrical properties of a one-dimensional (1D) rhodium(I)-semiquinonato complex,
      [Rh(3,6-DBSQ-4,5-(MeO)2)(CO)2]infinity (3), where 3,6-DBSQ-4,5-(MeO)2(*-)
      represents 3,6-di-tert-butyl-4,5-dimethoxy-1,2-benzosemiquinonato radical anion.
      The compound 3 comprises neutral 1D chains of complex molecules stacked in a
      staggered arrangement with short Rh-Rh distances of 3.0796(4) and 3.1045(4) A at
      226 K and exhibits unprecedented bistable multifunctionality with respect to its
      magnetic and conductive properties in the temperature range of 228-207 K. The
      observed bistability results from the thermal hysteresis across a first-order
      phase transition, and the transition accompanies the exchange of the interchain C
      H...O hydrogen-bond partners between the semiquinonato ligands. The strong
      overlaps of the complex molecules lead to unusually strong ferromagnetic
      interactions in the low-temperature (LT) phase. Furthermore, the magnetic
      interactions in the 1D chain drastically change from strongly ferromagnetic in
      the LT phase to antiferromagnetic in the room-temperature (RT) phase with
      hysteresis. In addition, the compound 3 exhibits long-range antiferromagnetic
      ordering between the ferromagnetic chains and spontaneous magnetization because
      of spin canting (canted antiferromagnetism) at a transition temperature T(N) of
      14.2 K. The electrical conductivity of 3 at 300 K is 4.8 * 10(-4) S cm(-1), which
      is relatively high despite Rh not being in a mixed-valence state. The temperature
      dependence of electrical resistivity also exhibits a clear hysteresis across the
      first-order phase transition. Furthermore, the ferromagnetic LT phase can be
      easily stabilized up to RT by the application of a relatively weak applied
      pressure of 1.4 kbar, which reflects the bistable characteristics and
      demonstrates the simultaneous control of multifunctionality through external
      perturbation.

PMID- 24749986
TI  - Simultaneous quantification of vitamin D3, 25-hydroxyvitamin D3 and 24,25
      dihydroxyvitamin D3 in human serum by LC-MS/MS.
AB  - INTRODUCTION: Serum 25-hydroxy-vitamin D is the established biomarker of vitamin
      D status although serum concentrations of vitamin D and 24,25-dihydroxyvitamin D
      may also be of interest to understand the in vivo kinetics of serum 25
      hydroxyvitamin D. METHOD: An LC-MS/MS method was developed and validated to
      quantify vitamin D3, 25-hydroxyvitamin D3 and 24,25-dihydroxyvitamin D3 in serum.
      After protein precipitation of the serum it was loaded on a HybridSPE column to
      separate vitamin D metabolites from phospholipids. Vitamin D3, 25-hydroxyvitamin
      D3 and 24,25-dihydroxyvitamin D3 in the eluate were derivatized by 4-phenyl-1,2,4
      triazoline-3,5-dione to improve sensitivity in the following LC-MS/MS analysis.
      RESULTS: Using only 100 MUL serum the limit of quantification was < 0.2 ng/mL for
      vitamin D3, 25-hydroxyvitamin D3 and 24,25-dihydroxyvitamin D3. The method was
      validated up to 100 ng/mL (260 nmol/L) for vitamin D3, up to 100 ng/mL (240
      nmol/L) for 24,25-dihydroxyvitamin D3 and up to 200 ng/mL (499 nmol/L) for 25
      hydroxyvitamin D3. Precision was < 6.5% for vitamin D3 and 25-hydroxyvitamin D3
      and < 10.2% for 24,25-dihydroxyvitamin D3. CONCLUSION: We demonstrate that a
      method including not only serum 25-hydroxyvitamin D3 but also vitamin D3 and
      24,25-dihydroxyvitamin D3 could easily be implemented in most modern biochemical
      laboratories. The method could be used to study the metabolism of endogenous
      synthesized vitamin D3 as well as vitamin D3 in intervention studies.

PMID- 24749987
TI  - Bacterial contamination of surgical scrub suits worn outside the operating
      theatre: a randomised crossover study.
AB  - In this study, we aimed to evaluate the bacterial contamination of surgical scrub
      suits worn outside the operating theatre. We randomised 16 anaesthetists on
      separate occasions into one of 3 groups: restricted to the operating theatre
      only; theatre and surgical wards; and theatre and departmental office. For each
      group, sample fabric pieces attached to the chest, waist and hip areas of each
      suit were removed at 150 min intervals between 08:30 and 16:00 on the day of
      study, and sent for microbiological assessment. Mean bacterial counts increased
      significantly over the course of the working day (p = 0.036), and were lower in
      the chest compared to the hip (p = 0.007) and waist areas (p = 0.016). The mean
      (SD) bacterial counts, expressed as colony-forming units per cm(2) at 16:00 on
      the day of study, were 25.2 (43.5) for those restricted to theatre and 18.5
      (25.9) and 17.9 (31.0) for those allowed out to visit the ward and office,
      respectively (p = 0.370). We conclude that visits to ward and office did not
      significantly increase bacterial contamination of scrub suits.

PMID- 24749988
TI  - What is and what could have been: an ERP study on counterfactual comparisons.
AB  - Prior research indicates that the feedback-related negativity (FRN) reflects a
      good versus bad evaluation of decision outcomes, which is insensitive to the
      local utilitarian relation between chosen and unchosen outcomes. We tested
      whether this negative finding holds when the chosen outcome has an objective
      value of zero and therefore a comparison with the unchosen outcome is needed to
      identify overall choice valence. Participants completed a gambling task in which
      chosen and unchosen options could result in monetary wins, losses, or breaking
      even. Results show that the FRN does not reflect local favorableness but rather a
      dichotomy of gain versus no-gain for both chosen and unchosen outcomes. In
      contrast, P300 amplitude appears to reflect motivational salience derived from
      counterfactual comparisons of chosen and unchosen outcomes. Based on our and
      prior findings, we propose a threefold taxonomy of contextual factors and their
      relation to the FRN. 

PMID- 24749989
TI  - Integrated evaluation of cost, emissions, and resource potential for algal
      biofuels at the national scale.
AB  - Costs, emissions, and resource availability were modeled for the production of 5
      billion gallons yr(-1) (5 BGY) of renewable diesel in the United States from
      Chlorella biomass by hydrothermal liquefaction (HTL). The HTL model utilized data
      from a continuous 1-L reactor including catalytic hydrothermal gasification of
      the aqueous phase, and catalytic hydrotreatment of the HTL oil. A biophysical
      algae growth model coupled with weather and pond simulations predicted biomass
      productivity from experimental growth parameters, allowing site-by-site and
      temporal prediction of biomass production. The 5 BGY scale required
      geographically and climatically distributed sites. Even though screening down to
      5 BGY significantly reduced spatial and temporal variability, site-to-site,
      season-to-season, and interannual variations in productivity affected economic
      and environmental performance. Performance metrics based on annual average or
      peak productivity were inadequate; temporally and spatially explicit computations
      allowed more rigorous analysis of these dynamic systems. For example, 3-season
      operation with a winter shutdown was favored to avoid high greenhouse gas
      emissions, but economic performance was harmed by underutilized equipment during
      slow-growth periods. Thus, analysis of algal biofuel pathways must combine
      spatiotemporal resource assessment, economic analysis, and environmental analysis
      integrated over many sites when assessing national scale performance. 

PMID- 24749990
TI  - Controlling the Al-doping profile and accompanying electrical properties of
      rutile-phased TiO2 thin films.
AB  - The role of Al dopant in rutile-phased TiO2 films in the evaluation of the
      mechanism of leakage current reduction in Al-doped TiO2 (ATO) was studied in
      detail. The leakage current of the ATO film was strongly affected by the Al
      concentration at the interface between the ATO film and the RuO2 electrode. The
      conduction band offset of the interface increased with the increase in the Al
      dopant concentration in the rutile TiO2, which reduced the leakage current in the
      voltage region pertinent to the next-generation dynamic random access memory
      application. However, the Al doping in the anatase TiO2 did not notably increase
      the conduction band offset even with a higher Al concentration. The detailed
      analyses of the leakage conduction mechanism based on the quantum mechanical
      transfer-matrix method showed that Schottky emission and Fowler-Nordheim
      tunneling was the dominant leakage conduction mechanism in the lower and higher
      voltage regions, respectively. The chemical analyses using X-ray photoelectron
      spectroscopy corroborated the electrical test results. 

PMID- 24749991
TI  - Understanding the dandruff scalp before and after treatment: an in vivo Raman
      spectroscopic study.
AB  - OBJECTIVES: To study and characterize the stratum corneum (SC) of dandruff scalp
      using in vivo Raman spectroscopy, to study how it compares with the non-dandruff
      scalp and to see the effect of treatment with a zinc pyrithione (ZnPTO)-based
      anti-dandruff shampoo. METHODS: The scalp skin was measured using a recently
      developed in vivo Raman probe. This method allows the inherent molecular
      components of the SC to be measured in vivo and confocally with depth, in
      particular the levels of natural moisturizing factors (NMF), lipids, lactic acid,
      urea and water. RESULTS: Depth-profile data for the skin components in dandruff
      SC in vivo are shown for the first time. The dandruff SC has lower NMF than the
      non-dandruff SC (0.16 compared with 0.39 a.u.), lower hydration, elevated levels
      of urea and lower levels of lactic acid. Treatment with an anti-dandruff shampoo
      containing 1% ZnPTO substantially restores the levels of each of these components
      close to the non-dandruff levels. Further to this, it is shown that sebum
      penetrates deeper into dandruff SC and at higher levels compared with non
      dandruff SC. The levels of sebum localized within the SC are also brought closer
      to those of the non-dandruff condition after ZnPTO treatment. CONCLUSION: The in
      vivo Raman probe has allowed the direct measurement of dandruff-affected skin in
      situ for the first time. It has been shown that the dandruff SC is different from
      that of the non-dandruff scalp and that it is changed by treatment with shampoo
      containing ZnPTO and brought towards the characteristics of non-dandruff scalp.
      It offers novel insights into how the nature of a healthy scalp should be
      defined.

PMID- 24749992
TI  - Thrombolytic-related complication in a case of misdiagnosed myocardial
      infarction.
AB  - The importance of early thrombolysis in acute myocardial infarction has been
      highlighted in several large trials. The clinical decision is often taken by
      physicians who need to take a rapid action with the risk of misdiagnosing non
      coronary events that mimic myocardial infarction. Here we describe a case of
      acute pericarditis in a 37-year-old man whom received thrombolysis and developed
      a sudden hemorrhagic pericardial effusion that evolved rapidly into a cardiac
      tamponade. These errors leading to lethal thrombolysis complications have been
      surprisingly rare; but a correct diagnosis of aortic dissection or hemorrhagic
      pericarditis needs to be stressed because even after obtaining the correct
      diagnosis, the prolonged disturbance of hemostasis prevents a rapid therapy being
      instigated.

PMID- 24749993
TI  - Psychometric properties of the Differentiation of Self Inventory-Revised in
      Turkish adults.
AB  - The purpose of the current study was to examine the validity and reliability of
      (Journal of Marital and Family Therapy 2003, 29, 209) Differentiation of Self
      Inventory-Revised (DSI-R; Skowron & Schmit, 2003) in Turkish adults. The DSI-R
      was translated, independently back-translated, and revised. Two independent
      samples of adults over the age of 25 were used. The original 46-item DSI-R was
      not supported by the data derived from Sample 1 (n = 221). However, a revised 20
      item, four-factor model fit the data well. This 20-item model was subsequently
      cross-validated with a second sample of Turkish adults (n = 187). Scale scores
      showed adequate internal consistency, 5-week test-retest reliability, and
      satisfactory convergent and criterion-related validity. It was concluded that
      Turkish DSI-R (DSI-T) is a valid and reliable measure to assess an individual's
      differentiation level. In light of the findings, implications for the use of the
      DSI-T and ideas for future research are discussed.

PMID- 24749995
TI  - Self-assembly of nanoparticles: a snapshot.

PMID- 24749994
TI  - Effect of impeller design and spacing on gas exchange in a percutaneous
      respiratory assist catheter.
AB  - Providing partial respiratory assistance by removing carbon dioxide (CO2 ) can
      improve clinical outcomes in patients suffering from acute exacerbations of
      chronic obstructive pulmonary disease and acute respiratory distress syndrome. An
      intravenous respiratory assist device with a small (25 Fr) insertion diameter
      eliminates the complexity and potential complications associated with external
      blood circuitry and can be inserted by nonspecialized surgeons. The impeller
      percutaneous respiratory assist catheter (IPRAC) is a highly efficient CO2
      removal device for percutaneous insertion to the vena cava via the right jugular
      or right femoral vein that utilizes an array of impellers rotating within a
      hollow-fiber membrane bundle to enhance gas exchange. The objective of this study
      was to evaluate the effects of new impeller designs and impeller spacing on gas
      exchange in the IPRAC using computational fluid dynamics (CFD) and in vitro
      deionized water gas exchange testing. A CFD gas exchange and flow model was
      developed to guide a progressive impeller design process. Six impeller blade
      geometries were designed and tested in vitro in an IPRAC device with 2- or 10-mm
      axial spacing and varying numbers of blades (2-5). The maximum CO2 removal
      efficiency (exchange per unit surface area) achieved was 573 +/- 8 mL/min/m(2)
      (40.1 mL/min absolute). The gas exchange rate was found to be largely independent
      of blade design and number of blades for the impellers tested but increased
      significantly (5-10%) with reduced axial spacing allowing for additional shaft
      impellers (23 vs. 14). CFD gas exchange predictions were within 2-13% of
      experimental values and accurately predicted the relative improvement with
      impellers at 2- versus 10-mm axial spacing. The ability of CFD simulation to
      accurately forecast the effects of influential design parameters suggests it can
      be used to identify impeller traits that profoundly affect facilitated gas
      exchange.

PMID- 24749998
TI  - Pseudopeptidic cages as receptors for N-protected dipeptides.
AB  - The molecular recognition of short peptides is a challenge in supramolecular
      chemistry, and the use of peptide-like cage receptors represents a promising
      approach. Here we report the synthesis and characterization of a diverse family
      of pseudopeptidic macrobicycles, as well as their binding abilities toward N
      protected dipeptides using a combination of different techniques (NMR, ESI-MS,
      and fluorescence spectroscopy). The cage hosts were assayed for dipeptide binding
      using competition ESI-MS experiments as high-throughput screening to obtain
      general trends for the recognition phenomena. Selected hosts were additionally
      studied by NMR spectroscopy ((1)H NMR titration and diffusion-ordered
      spectroscopy experiments) in different solvents. The results unambiguously
      demonstrated the formation of the [cage.dipeptide] supramolecular complexes and
      rendered quantitative information about the strength of the interaction (K(ass)).
      The structural variables within the pseudopeptidic cage framework that produced a
      stronger and more selective recognition were thus identified. The cages showed a
      remarkable selectivity for N-protected dipeptides with an aromatic amino acid at
      the carboxylic terminus, which prompted us to propose a mode of binding based on
      polar and nonpolar noncovalent interactions. Accordingly, we faced the molecular
      recognition of a target dipeptide (Ac-EY-OH) mimicking a biologically relevant
      sequence by NMR and fluorescence spectroscopy in highly competitive media.

PMID- 24749999
TI  - Non Tumor Perfusion Changes Following Stereotactic Radiosurgery to Brain
      Metastases.
AB  - Purpose: To evaluate early perfusion changes in normal tissue following
      stereotactic radiosurgery (SRS). Methods: Nineteen patients harboring twenty-two
      brain metastases treated with SRS were imaged with dynamic susceptibility
      magnetic resonance imaging (DSC MRI) at baseline, 1 week and 1 month post SRS.
      Relative cerebral blood volume and flow (rCBV and rCBF) ratios were evaluated
      outside of tumor within a combined region of interest (ROI) and separately within
      gray matter (GM) and white matter (WM) ROIs. Three-dimensional dose distribution
      from each SRS plan was divided into six regions: (1) <2 Gy; (2) 2-5 Gy; (3) 5-10
      Gy; (4) 10-12 Gy; (5) 12-16 Gy; and (6) >16 Gy. rCBV and rCBF ratio differences
      between baseline, 1 week and 1 month were compared. Best linear fit plots
      quantified normal tissue dose-dependency. Results: Significant rCBV ratio
      increases were present between baseline and 1 month for all ROIs and dose ranges
      except for WM ROI receiving <2 Gy. rCBV ratio for all ROIs was maximally
      increased from baseline to 1 month with the greatest changes occurring within the
      5-10 Gy dose range (53.1%). rCBF ratio was maximally increased from baseline to 1
      month for all ROIs within the 5-10 Gy dose range (33.9-45.0%). Both rCBV and rCBF
      ratios were most elevated within GM ROIs. A weak, positive but not significant
      association between dose, rCBV and rCBF ratio was demonstrated. Progressive rCBV
      and rCBF ratio increased with dose up to 10 Gy at 1 month. Conclusion: Normal
      tissue response following SRS can be characterized by dose, tissue, and time
      specific increases in rCBV and rCBF ratio.

PMID- 24750000
TI  - Adenovirus-mediated ING4 Gene Transfer in Osteosarcoma Suppresses Tumor Growth
      via Induction of Apoptosis and Inhibition of Tumor Angiogenesis.
AB  - The inhibitor of growth (ING) family proteins have been defined as candidate
      tumor suppressors. ING4 as a novel member of ING family has potential tumor
      suppressive effects via multiple pathways. However, the therapeutic effect of
      adenovirus-mediated ING4 (Ad-ING4) gene transfer in human osteosarcoma is still
      unknown. In this study, we explored the in vitro and in vivo antitumor activity
      of Ad-ING4 in human osteosarcoma and its potential mechanism using a MG-63 human
      osteosarcoma cell line. We demonstrated that Ad-ING4 induced significant growth
      inhibition and apoptosis, upregulated the expression of P21, P27 and Bax,
      downregulated the Bcl-2 expression and activated Caspase-3 in MG-63 human
      osteosarcoma cells. Moreover, intratumoral injections of Ad-ING4 in athymic nude
      mice bearing MG-63 human osteosarcoma tumors significantly suppressed
      osteosarcoma xenografted tumor growth, increased the expression of P21, P27 and
      Bax, reduced the Bcl-2 and CD34 expression and microvessel density (MVD) in
      tumors. This retarded MG-63 osteosarcoma growth in vitro and in vivo in an
      athymic nude mouse model elicited by Ad-ING4 was closely associated with the
      increase in the expression of cell cycle-related molecules P21 and P27, decrease
      in the ratio of anti- to pro-apoptotic molecules Bcl-2/Bax followed by the
      activation of Caspase-3 leading to apoptosis via intrinsic apoptotic pathways,
      and the inhibition of tumor angiogenesis. Thus, our results indicate that Ad-ING4
      is a potential candidate for human osteosarcoma gene therapy. 

PMID- 24750002
TI  - Tumor Directed, Scalp Sparing Intensity Modulated Whole Brain Radiotherapy for
      Brain Metastases.
AB  - Despite significant technical advances in radiation delivery, conventional whole
      brain radiation therapy (WBRT) has not materially changed in the past 50 years.
      We hypothesized that IMRT can selectively spare uninvolved brain and scalp with
      the goal of reducing acute and late toxicity. MRI/CT simulation image
      registration was performed. We performed IMRT planning to simultaneously treat
      the brain tumor(s) on MRI + 5 mm margin to 37.5 Gy in 15 fractions while limiting
      the uninvolved brain + 2 mm margin to 30 Gy in 15 fractions and the mean scalp
      dose to #18 Gy. Three field IMRT plans were compared to conventional WBRT plans.
      Symptomatic patients were started on conventional WBRT for 2 to 3 fractions while
      IMRT planning was performed. Seventeen consecutive patients with brain metastases
      with RPA class I and II disease with no leptomeningeal spread were treated with
      IMRT WBRT. Compared to conventional WBRT, IMRT reduced the mean scalp dose (26.2
      Gy vs. 16.4 Gy, p < 0.001) and the mean PTV30 dose (38.4 Gy vs. 32.0 Gy, p <
      0.001) while achieving similar mean PTV37.5 doses (38.3 Gy vs. 38.0 Gy, p =
      0.26). Using Olsen hair loss score criteria, 4 of 15 assessable patients
      preserved at least 50% of hair coverage at 1 to 3 months after treatment while 6
      patients preserved between 25 and 50% hair coverage. At a median follow-up of 6.8
      months (range: 5 to 15 months), the median overall survival was 5.4 months. Four
      patients relapsed within the brain, one within the PTV37.5 and three outside the
      PTV37.5. Tumor directed, scalp sparing IMRT is feasible, achieves rational dose
      distributions and preserves partial hair coverage in the majority of patients.
      Further studies are warranted to determine whether the increased utilization of
      resources needed for IMRT are appropriate in this setting. 

PMID- 24750001
TI  - Outcome Study of Cobalt Based Stereotactic Body Radiation Therapy for Patients
      with Inoperable Stage III Non-small Cell Lung Cancer.
AB  - Aim of this paper is to retrospectively evaluate the efficacy and toxicity of
      specialized Body Cobalt based system (BCBS) treatment in the senior patients
      group (.65 years) with Stage III non-small cell lung carcinoma (NSCLC). A total
      of 49 patients (41 males and 8 females) with Stage III NSCLC according to UICC
      TNM classification (6(th) edition) were treated using OUR-QGDTM BCBS which was
      designed and manufactured in China. Post treatment evaluation with follow-up
      information was collected from April 2001 to December 2006 in our department.
      Median age of enrolled patients was 71 years old (65-85). Among those patients,
      36 patients were pathologically identified with squamous cell carcinoma, and the
      other 13 patients were confirmed as adenocarcinoma. All patients were immobilized
      by vacuum based immobilization mold and then performed slow CT scan without any
      respiration gating devices. The daily radiation prescription dose was defined at
      50% isodose line covering primary lesions and metastatic lymph nodes with doses
      from 2.5 to 6 Gy in 5 fractions per week according to the tumor stage and
      internally approved treatment protocols by the Institutional Review Board (IRB).
      Median daily dose and total delivery dose of 50% isodose line were 4 Gy and 41
      Gy, respectively. In this study group, total of 3 patients received neoadjuvant
      cisplatin-based chemotherapy. Tumor response evaluated 12 weeks after radiation
      has demonstrated 13 complete responses (26.5%), 21 partial responses (42.9%). The
      overall survival (OS) rate of 1-year, 2-year and 3-year was 63.3%, 40.8% and
      20.4%, respectively. The median and mean survival time was 22 and 24 months. All
      49 patients tolerated the treatment well and have completed the planned therapy
      regiment. Body Cobalt based system treatment of those over 65 years old patients
      with Stage III NSCLC had reasonable and superior curative effect as well as local
      control, and at the same time without severe radiation side effects. 

PMID- 24750003
TI  - Radiosurgery with Helical Tomotherapy: Outcomes for Patients with One or
      Multifocal Brain Metastasis.
AB  - To evaluate the feasibility and report the preliminary results for stereotactic
      radiosurgery (SRS) treatments of single or multiple brain metastases delivered
      with helical tomotherapy (HT) by means of the InterFixTM Radiosurgery kit.
      Between September 2010 and August 2012, thirty patients underwent SRS for
      treatment of 46 brain metastases with a median prescription dose of 20 Gy (range
      15-21 Gy). Clinical response was assessed with 2-3 month intervals by magnetic
      resonance imaging (MRI). Dose distribution indexes were computed and compared
      with published data for SRS performed with dedicated machines. After a median
      follow-up of 14 months (range 4-31) the estimated overall survival (OS) rate was
      70% at 6 months, 60% at 12 months and 44% at 18 months. Local control (LC) was
      72% at 6 months, 65% at 12 months and 50% at 18 months. Acute toxicity as
      headache and epileptic crisis occurred in only two patients. The mean values of
      conformity, homogeneity and gradient score indexes were 1.36, 1.04 and 50
      respectively. HT-SRS for single or multiple brain metastases appears a reliable
      technique with encouraging clinical outcomes and competitive dosimetrical
      results. 

PMID- 24750004
TI  - Folate Conjugated Cellulose Nanocrystals Potentiate Irreversible Electroporation
      induced Cytotoxicity for the Selective Treatment of Cancer Cells.
AB  - Cellulose nanocrystals are rod-shaped, crystalline nanoparticles that have shown
      prom-ise in a number of industrial applications for their unique chemical and
      physical properties. However, investigations of their abilities in the biomedical
      field are limited. The goal of this study is to show the potential use of folic
      acid-conjugated cellulose nanocrystals in the potentiation of irreversible
      electroporation-induced cell death in folate receptor (FR)-positive cancers. We
      optimized key pulse parameters including pulse duration, intensity, and
      incubation time with nanoparticles prior to electroporation. FR-positive cancer
      cells, KB and MDA-MB-468, were preincubated with cellulose nanocrystals (CNCs)
      conjugated with the targeting molecule folic acid (FA), 10 and 20 min
      respectively, prior to application of the optimized pulse electric field (PEF),
      600 and 500 V/cm respectively. We have shown cellulose nanocrystals' ability to
      potentiate a new technique for tumor ablation, irreversible electroporation. Pre
      incubation with FA-conjugated CNCs (CNC-FA) has shown a significant increase in
      cytotoxicity induced by irreversible electroporation in FR-positive cancer cells,
      KB and MDA-MB-468. Non-targeted CNCs (CNC-COOH) did not potentiate IRE when
      preincubated at the same parameters as previously stated in these cell types. In
      addition, CNC-FA did not potentiate irreversible electroporation-induced
      cytotoxicity in a FR-negative cancer cell type, A549. Without changing
      irreversible electroporation parameters it is possible to increase the cytotoxic
      effect on FR-positive cancer cells by exploiting the specific binding of FA to
      the FR, while not causing further damage to FR-negative tissue. 

PMID- 24750005
TI  - A Fully GPU-Based Ray-Driven Backprojector via a Ray-Culling Scheme with Voxel
      Level Parallelization for Cone-Beam CT Reconstruction.
AB  - A ray-driven backprojector is based on ray-tracing, which computes the length of
      the intersection between the ray paths and each voxel to be reconstructed. To
      reduce the computational burden caused by these exhaustive intersection tests, we
      propose a fully graphics processing unit (GPU)-based ray-driven backprojector in
      conjunction with a ray-culling scheme that enables straightforward
      parallelization without compromising the high computing performance of a GPU. The
      purpose of the ray-culling scheme is to reduce the number of ray-voxel
      intersection tests by excluding rays irrelevant to a specific voxel computation.
      This rejection step is based on an axis-aligned bounding box (AABB) enclosing a
      region of voxel projection, where eight vertices of each voxel are projected onto
      the detector plane. The range of the rectangular-shaped AABB is determined by
      min/max operations on the coordinates in the region. Using the indices of pixels
      inside the AABB, the rays passing through the voxel can be identified and the
      voxel is weighted as the length of intersection between the voxel and the ray.
      This procedure makes it possible to reflect voxel-level parallelization, allowing
      an independent calculation at each voxel, which is feasible for a GPU
      implementation. To eliminate redundant calculations during ray-culling, a shared
      memory optimization is applied to exploit the GPU memory hierarchy. In
      experimental results using real measurement data with phantoms, the proposed GPU
      based ray-culling scheme reconstructed a volume of resolution 28032803176 in 77
      seconds from 680 projections of resolution 10243768 , which is 26 times and 7.5
      times faster than standard CPU-based and GPU-based ray-driven backprojectors,
      respectively. Qualitative and quantitative analyses showed that the ray-driven
      backprojector provides high-quality reconstruction images when compared with
      those generated by the Feldkamp-Davis-Kress algorithm using a pixel-driven
      backprojector, with an average of 2.5 times higher contrast-to-noise ratio, 1.04
      times higher universal quality index, and 1.39 times higher normalized mutual
      information. 

PMID- 24750006
TI  - Development of an Automated Medical Diagnosis System for Classifying Thyroid
      Tumor Cells using Multiple Classifier Fusion.
AB  - An automated medical diagnosis system has been developed to discriminate benign
      and malignant thyroid nodules in multi-stained fine needle aspiration biopsy
      (FNAB) images using multiple classifier fusion and presented in this paper.
      First, thyroid cell regions are extracted from the auto-cropped sub-image by
      implementing mathematical morphology segmentation method. Subsequently,
      statistical features are extracted by two-level wavelet decomposition based on
      texture characteristics of the thyroid cells. After that, decision tree (DT), k
      nearest neighbor (k-NN), Elman neural network (ENN) and support vector machine
      (SVM) classifiers are used separately to classify thyroid nodules into benign and
      malignant. The four individual classifier outputs are then fused together using
      majority voting rule and linear combination rules to improve the performance of
      the diagnostic system. The classification results of ENN and SVM classifiers show
      an overall diagnostic accuracy (DA) of 90%, sensitivity (Se) of 85% and 100%,
      specificity (Sp) of 90% and 90% respectively. However, the best diagnostic
      accuracy of 96.66% is obtained by multiple classifier fusion with majority voting
      rule and linear combination rules. The experimental results show that the
      proposed method is a useful tool for the diagnosis of thyroid cancer and can
      provide a second opinion for a physician's decision. 

PMID- 24750007
TI  - The Technique, Resources and Costs of Stereotactic Body Radiotherapy of Prostate
      Cancer: A Comparison of Dose Regimens and Delivery Systems.
AB  - Robotic system has been used for stereotactic body radiotherapy (SBRT) of
      prostate cancer. Arc-based and fixed-gantry systems are used for hypofractionated
      regimens (10-20 fractions) and the standard regimen (39 fractions); they may also
      be used to deliver SBRT. Studies are currently underway to compare efficacy and
      safety of these systems and regimens. Thus, we describe the technique and
      required resources for the provision of robotic SBRT in relation to the standard
      regimen and other systems to guide investment decisions. Using administrative
      data of resource volumes and unit prices, we computed the cost per patient, cost
      per cure and cost per quality adjusted life year (QALY) of four regimens (5, 12,
      20 and 39 fractions) and three delivery systems (robotic, arc-based and fixed
      gantry) from a payer's perspective. We performed sensitivity analyses to examine
      the effects of daily hours of operation and in-room treatment delivery times on
      cost per patient. In addition, we estimated the budget impact when a robotic
      system is preferred over an arc-based or fixed-gantry system. Costs of SBRT were
      $6333/patient (robotic), $4368/patient (arc-based) and $4443/patient (fixed
      gantry). When daily hours of operation were varied, the cost of robotic SBRT
      varied from $9324/patient (2 hours daily) to $5250/patient (10 hours daily). This
      was comparable to the costs of 39 fraction standard regimen which were
      $5935/patient (arc-based) and $7992/ patient (fixed-gantry). In settings of
      moderate to high patient volume, robotic SBRT is cost effective compared to the
      standard regimen. If SBRT can be delivered with equivalent efficacy and safety,
      the arc-based system would be the most cost effective system.

PMID- 24750009
TI  - Fungal associations in Horneophyton ligneri from the Rhynie Chert (c. 407 million
      year old) closely resemble those in extant lower land plants: novel insights into
      ancestral plant-fungus symbioses.
AB  - Fungi (Eumycota) form close associations with plants, with which they have co
      existed since the dawn of life on land, but their diversity in early terrestrial
      ecosystems is still poorly understood. We studied petrographic sections of
      exceptionally well-preserved petrified plants from the 407 million yr-old Rhynie
      Chert (Scotland, UK). For comparative purposes, we illustrate fungal associations
      in four extant lower land plants. We document two new endophytes in the plant
      Horneophyton lignieri: Palaeoglomus boullardii (sp. nov. Glomeromycota) colonizes
      parenchyma in a discontinuous zone of the outer cortex of the aerial axes,
      forming arbuscule-like structures, vesicles and spores; Palaeoendogone gwynne
      vaughaniae (gen. nov., sp. nov. Mucoromycotina) colonizes parenchyma in the basal
      part of the plant, where it is present in intercellular spaces and as
      intracellular coils but absent from rhizoids. Critical comparisons between the
      newly discovered Horneophyton endophytes, fungi previously described from the
      Rhynie Chert and fungal colonization in extant lower land plants reveal several
      features characteristic of both Mucoromycotina and Glomeromycota. A reappraisal
      of fungal associations in early land plants indicates that they are more diverse
      than assumed hitherto, overturning the long-held paradigm that the early
      endophytes were exclusively Glomeromycota. 

PMID- 24750010
TI  - Large-scale team-based learning for interprofessional education in medical and
      health sciences.

PMID- 24750012
TI  - Synthesis and self-assembly of amphiphilic aptamer-functionalized hyperbranched
      multiarm copolymers for targeted cancer imaging.
AB  - A novel targeting cancer imaging platform based on aptamer-functionalized
      amphiphilic hyperbranched copolymer conjugates, which can self-assemble into
      nanoscopic micelles with a core-shell structure and a narrow size distribution,
      has been designed and synthesized. The size, morphology, fluorescence
      performance, and cytotoxicity of micelles were studied by dynamic light
      scattering, transmission electron microscopy, fluorescence spectroscopy, and a 3
      (4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide colorimetric assay.
      The results indicate that these micelles have low cytotoxicity against MCF-7
      cells and can be easily internalized by MCF-7 cells. In addition, they also
      exhibit enhanced cell uptake, excellent fluorescence properties, and smart
      targeting capability in vitro, indicating great potential to be promising
      carriers for bioimaging and cancer specific delivery. 

PMID- 24750013
TI  - A pilot study of cerebral tissue oxygenation and postoperative cognitive
      dysfunction among patients undergoing coronary artery bypass grafting randomised
      to surgery with or without cardiopulmonary bypass*.
AB  - Coronary artery bypass surgery, performed with or without cardiopulmonary bypass,
      is frequently followed by postoperative cognitive decline. Near-infrared
      spectroscopy is commonly used to assess cerebral tissue oxygenation, especially
      during cardiac surgery. Recent studies have suggested an association between
      cerebral desaturation and postoperative cognitive dysfunction. We therefore
      studied cerebral oxygen desaturation, defined as area under the cerebral
      oxygenation curve < 40% of > 10 min.%, with respect to cognitive performance at 4
      days (early) and 3 months (late) postoperatively, compared with baseline, using a
      computerised cognitive test battery. We included 60 patients, of mean (SD) age
      62.8 (9.4) years, scheduled for elective coronary artery bypass grafting, who
      were randomly allocated to surgery with or without cardiopulmonary bypass.
      Cerebral desaturation occurred in only three patients and there was no difference
      in cerebral oxygenation between the two groups at any time. Among patients who
      received cardiopulmonary bypass, 18 (62%) had early cognitive decline, compared
      with 16 (53%) in the group without cardiopulmonary bypass (p = 0.50). Three
      months after surgery, 11 patients (39%) in the cardiopulmonary bypass group
      displayed cognitive dysfunction, compared with four (14%) in the non
      cardiopulmonary bypass group (p = 0.03). The use of cardiopulmonary bypass was
      identified as an independent risk factor for the development of late cognitive
      dysfunction (OR 6.4 (95% CI 1.2-33.0) p = 0.027. In conclusion, although cerebral
      oxygen desaturation was rare in our population, postoperative cognitive decline
      was common in both groups, suggesting that factors other than hypoxic neuronal
      injury are responsible.

PMID- 24750014
TI  - Effect of a toggle switch mutation in TM6 of the human adenosine A3 receptor on
      Gi protein-dependent signalling and Gi-independent receptor internalization.
AB  - BACKGROUND AND PURPOSE: The highly conserved tryptophan (W6.48) in transmembrane
      domain 6 of GPCRs has been shown to play a central role in forming an active
      conformation in response to agonist binding. We set out to characterize the
      effect of this mutation on the efficacy of two agonists at multiple signalling
      pathways downstream of the adenosine A3 receptor. EXPERIMENTAL APPROACH: Residue
      W6.48 in the human adenosine A3 receptor fused to yellow fluorescent protein was
      mutated to phenylalanine and expressed in CHO-K1 cells containing a cAMP response
      element reporter gene. The effects on agonist-mediated receptor internalization
      were monitored by automated confocal microscopy and image analysis. Further
      experiments were carried out to investigate agonist-mediated ERK1/2
      phosphorylation, inhibition of [(3)H]-cAMP accumulation and beta-arrestin2
      binding. KEY RESULTS: NECA was able to stimulate agonist-mediated internalization
      of the W6.48F mutant receptor, while the agonist HEMADO was inactive.
      Investigation of other downstream signalling pathways indicated that G-protein
      coupling was impaired for both agonists tested. Mutation of W6.48F therefore
      resulted in differential effects on agonist efficacy, and introduced signalling
      pathway bias for HEMADO at the adenosine A3 receptor. CONCLUSIONS AND
      IMPLICATIONS: Investigation of the pharmacology of the W6.48F mutant of the
      adenosine A3 receptor confirms that this region is important in forming the
      active conformation of the receptor for stimulating a number of different
      signalling pathways and that mutations in this residue can lead to changes in
      agonist efficacy and signalling bias.

PMID- 24750015
TI  - Reduced antiplatelet effect of aspirin during 24 hours in patients with coronary
      artery disease and type 2 diabetes.
AB  - Reduced antiplatelet effect of aspirin has been reported in patients with type 2
      diabetes, and recent studies suggest that once-daily aspirin provides
      insufficient platelet inhibition. We investigated if the effect of aspirin
      declined during the 24-hour dosing interval in patients with coronary artery
      disease and type 2 diabetes, and whether this correlated with increased platelet
      turnover. Furthermore, the intra-individual variation in platelet aggregation was
      determined during a 28-day period. We included 47 patients with coronary artery
      disease and type 2 diabetes treated with aspirin 75 mg daily. Blood samples were
      obtained 1 and 24 hours after aspirin intake, and this was repeated three times
      with a 2-week interval between each visit. Platelet aggregation was evaluated by
      impedance aggregometry (Multiplate(r) Analyzer) using arachidonic acid (1.0 mM)
      and collagen (3.2 ug/ml) as agonists. Markers of platelet turnover were measured
      by flow cytometry. Compliance was confirmed by serum thromboxane B2. Platelet
      aggregation levels measured 1 and 24 hours after aspirin intake were compared
      using the mean of 1- and 24-hour measurements at the three study visits. The
      difference in platelet aggregation was 70 +/- 97 AU * min (p < 0.0001) when using
      arachidonic acid as agonist and 33 +/- 76 AU * min (p = 0.01) when using
      collagen. Markers of platelet turnover correlated positively, though not
      significantly, with residual platelet aggregation 24 hours after aspirin intake
      (p values 0.06 and 0.07). Median intra-individual variation of platelet
      aggregation was 9-16%. Patients with coronary artery disease and type 2 diabetes
      had increased platelet aggregation at the end of the 24-hour aspirin dosing
      interval. Platelet turnover did not correlate significantly with residual
      platelet aggregation, although a trend was observed. The intra-individual
      variation of platelet aggregation after aspirin intake was low.

PMID- 24750016
TI  - Are different soil metals near the homes of pregnant women associated with mild
      and severe intellectual disability in children?
AB  - AIM: We explored the association of relatively low concentrations of metals in
      the soil proximal to maternal residence during pregnancy, with intellectual
      disability. We hypothesized different metals would be associated with mild versus
      severe intellectual disability. METHOD: We used a mixed methods design, starting
      with a retrospective cohort from 1996 to 2002, of 10,051 pregnant mothers, soil
      sampling in the areas where these mothers resided during pregnancy, and follow-up
      of their children to determine if there was an intellectual disability outcome.
      We tested the soil and then predicted the soil concentration at the maternal
      homes, and modeled the association with the severity of the child's intellectual
      disability. RESULTS: We found a significant positive association between mild
      intellectual disability and soil mercury (p=0.007). For severe intellectual
      disability, there was a significant positive association with the soil arsenic
      and lead (p=0.025). INTERPRETATION: This is the first report of the differential
      impact of metals in soil and severity of intellectual disability in children.
      Soil mercury concentration in the area the mother lived during pregnancy is
      associated with significantly increased odds of mild intellectual disability; a
      combination of arsenic and lead is associated with significantly increased odds
      of severe intellectual disability. These associations are present when
      controlling for maternal, child, and neighborhood characteristics.

PMID- 24750017
TI  - Treatment adherence in patients with headache: a systematic review.
AB  - OBJECTIVE: To review and critically evaluate the extant research literature
      pertaining to adherence in youth and adults with headache and to provide
      recommendations for future research. BACKGROUND: This article provides the first
      systematic review of pediatric headache adherence and updates a previous review
      of treatment adherence in adults with headache. DESIGN: Systematic review of
      empirical literature. METHODS: A literature search with no date restriction was
      conducted using PubMed and PsycINFO electronic databases and bibliographies of
      relevant articles. RESULTS: Adherence rates in adults with headache range
      considerably from 25% to 94% across treatment, assessment method, and definition
      of adherence utilized. Methods to assess adherence included retrospective
      prescription claims data, paper or electronic diaries, follow-up appointment
      attendance, written and verbal self-report of general adherence, verbal self
      report of adherence over a specific amount of time via in person interview or
      telephone, validated adherence measures, adherence questionnaires without
      validation, and counselor ratings of homework. Each methodology and assessment
      tool demonstrated strengths and weaknesses. No studies have systematically
      examined medication adherence in children with headache, and the few available
      studies examining adherence to behavioral treatment have documented adherence
      rates ranging from 52% to 86%. CONCLUSIONS: Adherence research in adults with
      headache is growing, but studies demonstrate a number of methodological
      shortcomings. Adherence research in children with headache, and adherence
      intervention research in both adults and children, is scant. Future research
      should use objective measures of adherence, consider over-the-counter medications
      and medication overuse, examine demographic, psychological, and behavioral
      correlates of adherence, assess adherence to botulinum toxin type A, and examine
      the efficacy of adherence interventions in individuals with headache.

PMID- 24750018
TI  - Is channel segmentation necessary to reach a multiethnic population with weight
      related health promotion? An analysis of use and perception of communication
      channels.
AB  - OBJECTIVE: To explore similarities and differences in the use and perception of
      communication channels to access weight-related health promotion among women in
      three ethnic minority groups. The ultimate aim was to determine whether similar
      channels might reach ethnic minority women in general or whether segmentation to
      ethnic groups would be required. DESIGN: Eight ethnically homogeneous focus
      groups were conducted among 48 women of Ghanaian, Antillean/Aruban, or Afro
      Surinamese background living in Amsterdam. Our questions concerned which
      communication channels they usually used to access weight-related health advice
      or information about programs and whose information they most valued. The content
      analysis of data was performed. RESULTS: The participants mentioned four channels
      - regular and traditional health care, general or ethnically specific media,
      multiethnic and ethnic gatherings, and interpersonal communication with peers in
      the Netherlands and with people in the home country. Ghanaian women emphasized
      ethnically specific channels (e.g., traditional health care, Ghanaian churches).
      They were comfortable with these channels and trusted them. They mentioned fewer
      general channels - mainly limited to health care - and if discussed, negative
      perceptions were expressed. Antillean women mentioned the use of ethnically
      specific channels (e.g., communication with Antilleans in the home country) on
      balance with general audience-oriented channels (e.g., regular health care).
      Perceptions were mixed. Surinamese participants discussed, in a positive manner,
      the use of general audience-oriented channels, while they said they did not use
      traditional health care or advice from Surinam. Local language proficiency, time
      resided in the Netherlands, and approaches and messages received seemed to
      explain channel use and perception. CONCLUSIONS: The predominant differences in
      channel use and perception among the ethnic groups indicate a need for channel
      segmentation to reach a multiethnic target group with weight-related health
      promotion. The study results reveal possible segmentation criteria besides
      ethnicity, such as local language proficiency and time since migration, worthy of
      further investigation.

PMID- 24750019
TI  - Cost-of-illness of patients with contact dermatitis in Denmark.
AB  - BACKGROUND: Contact dermatitis is a frequent occupational and non-occupational
      skin disease. OBJECTIVES: To investigate the effects of contact dermatitis on
      labour market affiliation and societal costs in terms of healthcare costs and
      production loss. METHODS: A total of 21 441 patients patch tested either in
      hospital departments or at dermatological clinics in the period 2004-2009 were
      included in the study. The analyses were stratified by children (age 0-15 years),
      occupational contact dermatitis (age 16-65 years), and non-occupational
      dermatitis (age >= 16 years). Controls were selected from a 30% random sample of
      the population. Individual encrypted data were retrieved on healthcare
      utilization, socio-demographics, education, labour market affiliation and
      transfer payments from public registers in Denmark for cases and controls.
      RESULTS: Attributable healthcare costs for 4 years prior to patch testing (1 year
      for children) and the year after patch testing were ?959 for children, ?724 for
      occupational contact dermatitis, and ?1794 for non-occupational dermatitis.
      Productivity costs for the same period were ?10 722 for occupational contact
      dermatitis and ?3074 for non-occupational contact dermatitis. CONCLUSIONS: The
      main findings of this study were that there were statistically significant
      attributable healthcare costs for both children and adults, and statistically
      significant productivity loss for adults.

PMID- 24750020
TI  - The role of CD33 as therapeutic target in acute myeloid leukemia.
AB  - CD33 is a myeloid differentiation antigen that is displayed on acute myeloid
      leukemia (AML) blasts in most patients and, possibly, leukemic stem cells in
      some, and has thus served as target for antibody-based therapies for many years.
      Validation for this approach comes from the antibody-drug conjugate, gemtuzumab
      ozogamicin, which improves survival of some patients with AML when added to
      induction chemotherapy. Still, CD33 is a challenging target because of its low
      expression and slow internalization; these characteristics limit antibody
      dependent cell-mediated cytotoxicity and intracellular drug accumulation and,
      consequently, the activity of unlabeled and toxin-carrying antibodies. Very
      promising preclinical data are now available from an improved antibody-drug
      conjugate and CD33-targeted strategies that redirect immune effector cells to
      eradicate the leukemia, most notably bispecific antibodies and chimeric antigen
      receptor T-cell immunotherapy. In parallel to their clinical testing, efforts
      will be needed to identify the patients that most likely benefit from such agents
      and the disease stage in which they are most efficacious. With enhanced activity
      of CD33-directed therapies, toxic effects on normal hematopoiesis will increase
      and require excellent supportive care measures, or even rescue with donor cells,
      to minimize morbidity and mortality from expected cytopenias and to optimize
      treatment outcomes with these therapeutics. 

PMID- 24750021
TI  - Large-scale synthesis of well-dispersed copper nanowires in an electric pressure
      cooker and their application in transparent and conductive networks.
AB  - We present a novel large-scale synthetic method for well-separated copper
      nanowires (CuNWs) in a commercial electric pressure cooker under mild reaction
      conditions. CuNWs (~2.1 g) can be prepared in a batch with the cost of $4.20/g.
      Well-dispersed polyvinylpyrrolidone-capped CuNWs were obtained via a ligand
      exchange method. The transparent and conductive CuNW networks with excellent
      electrical conductivity and high optical transmittance (30 Omega/? at 86%
      transmittance, respectively) were fabricated by a spin-coating process. 

PMID- 24750022
TI  - Comparing local TV news with national TV news in cancer coverage: an exploratory
      content analysis.
AB  - The authors compared local TV news with national TV news in terms of cancer
      coverage using a nationally representative sample of local nightly TV and
      national network TV (i.e., ABC, CBS, NBC, and CNN) cancer news stories that aired
      during 2002 and 2003. Compared with national TV news, local TV cancer stories
      were (a) much shorter in length, (b) less likely to report on cancer prevention
      (i.e., preventive behaviors and screening tests), and (c) less likely to
      reference national organizations (i.e., National Cancer Institute, American
      Cancer Society, National Institutes of Health, Centers for Disease Control and
      Prevention, Food and Drug Administration) that have made clear recommendations
      about ways to prevent cancer. The implications of these findings for health
      communication research and cancer education were discussed. 

PMID- 24750023
TI  - Effect of inert tails on the thermodynamics of DNA hybridization.
AB  - The selective hybridization of DNA is of key importance for many practical
      applications such as gene detection and DNA-mediated self-assembly. These
      applications require a quantitative prediction of the hybridization free energy.
      Existing methods ignore the effects of non-complementary ssDNA tails beyond the
      first unpaired base. We use experiments and simulations to show that the binding
      strength of complementary ssDNA oligomers is altered by these sequences of non
      complementary nucleotides. Even a small number of non-binding bases are enough to
      raise the hybridization free energy by approximately 1 kcal/mol at physiological
      salt concentrations. We propose a simple analytical expression that accounts
      quantitatively for this variation as a function of tail length and salt
      concentration. 

PMID- 24750024
TI  - Silicon interfacial passivation layer chemistry for high-k/InP interfaces.
AB  - The interfacial chemistry of thin (1 nm) silicon (Si) interfacial passivation
      layers (IPLs) deposited on acid-etched and native oxide InP(100) samples prior to
      atomic layer deposition (ALD) is investigated. The phosphorus oxides are
      scavenged completely from the acid-etched samples but not completely from the
      native oxide samples. Aluminum silicate and hafnium silicate are possibly
      generated upon ALD and following annealing. The thermal stability of a high
      k/Si/InP (acid-etched) stack are also studied by in situ annealing to 400 and 500
      degrees C under ultrahigh vacuum, and the aluminum oxide/Si/InP stack is the
      most thermally stable. An indium out-diffusion to the sample surface is observed
      through the Si IPL and the high-k dielectric, which may form volatile species and
      evaporate from the sample surface. 

PMID- 24750025
TI  - Removal of urea in a wearable dialysis device: a reappraisal of electro
      oxidation.
AB  - A major challenge for a wearable dialysis device is removal of urea, as urea is
      difficult to adsorb while daily production is very high. Electro-oxidation (EO)
      seems attractive because electrodes are durable, small, and inexpensive. We
      studied the efficacy of urea oxidation, generation of chlorine by-products, and
      their removal by activated carbon (AC). EO units were designed. Three electrode
      materials (platinum, ruthenium oxide, and graphite) were compared in single pass
      experiments using urea in saline solution. Chlorine removal by AC in series with
      EO by graphite electrodes was tested. Finally, urea-spiked bovine blood was
      dialyzed and dialysate was recirculated in a dialysate circuit with AC in series
      with an EO unit containing graphite electrodes. Platinum electrodes degraded more
      urea (21 +/- 2 mmol/h) than ruthenium oxide (13 +/- 2 mmol/h) or graphite
      electrodes (13 +/- 1 mmol/h). Chlorine generation was much lower with graphite
      (13 +/- 4 mg/h) than with platinum (231 +/- 22 mg/h) or ruthenium oxide
      electrodes (129 +/- 12 mg/h). Platinum and ruthenium oxide electrodes released
      platinum (4.1 [3.9-8.1] umol/h) and ruthenium (83 [77-107] nmol/h), respectively.
      AC potently reduced dialysate chlorine levels to < 0.10 mg/L. Urea was removed
      from blood by EO at constant rate (9.5 +/- 1.0 mmol/h). EO by graphite electrodes
      combined with AC shows promising urea removal and chlorine release complying with
      Association for the Advancement of Medical Instrumentation standards, and may be
      worth further exploring for dialysate regeneration in a wearable system.

PMID- 24750027
TI  - Has player development in men's tennis really changed? An historical rankings
      perspective.
AB  - Tennis federations are regularly faced with decisions regarding which athletes
      should be supported in financial terms, and for how long. The financial
      investments can be considerable, given the cost of competing on tour has been
      estimated at a minimum $121,000 per year and only the top 130 professionally
      ranked athletes earned enough prize money to cover this cost in 2012. This study
      investigates key points of progression in tennis players' careers, to determine
      how these have changed over time and how that evolution may inform talent
      development. Approximately 400,000 weekly rankings for 273 male professional
      tennis players between 1985 and 2010 were compiled, and historical trends in the
      time taken to reach career milestones were investigated by least-squares
      regression. The time between earning a first professional ranking point and entry
      into the Top 100 significantly increased over time for all considered athletes.
      This was at the detriment of time spent within the Top 100 for some athletes.
      Career peak Top 50-100 athletes have shown an increase in longevity. These
      results assist tennis federations in assessing the progress of developing
      athletes and highlight the evolving nature of the competition for top players.

PMID- 24750026
TI  - MBD5 regulates iron metabolism via methylation-independent genomic targeting of
      Fth1 through KAT2A in mice.
AB  - Ferritin plays important roles in iron metabolism and controls iron absorption in
      the intestine. The ferritin subunits ferritin heavy chain (Fth1) and ferritin
      light chain (Ftl1) are tightly regulated at both the transcriptional and post
      transcriptional levels. However, mechanisms of maintaining stable, basal
      expression of Fth1 are poorly understood. Here, we show that global deletion of
      Mbd5 in mice induces an iron overload phenotype. Liver and serum iron levels in
      Mbd5(-/-) mice were 3.2-fold and 1.5-fold higher respectively, than wild-type
      littermates; moreover, serum ferritin was increased >5-fold in the Mbd5(-/-)
      mice. Mbd5 encodes a member of the methyl-CpG binding domain family; however, the
      precise function of this gene is poorly understood. Here, we found that
      intestinal Fth1 mRNA levels were decreased in Mbd5(-/-) mice. Loss of Fth1
      expression in the intestine could lead to iron over-absorption. Furthermore,
      deleting Mbd5 specifically in the intestine resulted in a phenotype similar to
      that of conditional deletion of Fth1 mice. An Fth1 promoter-report luciferase
      assay indicated that overexpression of Mbd5 enhanced Fth1 transcription in a dose
      dependent manner. Histone H4 acetylation of the Fth1 promoter was reduced in the
      intestine of Mbd5(-/-) mice and further analysis showed that histone
      acetyltransferase KAT2A was essential for MBD5-induced Fth1 transcription. 

PMID- 24750028
TI  - One-pot synthesis of ureas from Boc-protected amines.
AB  - A practical one-pot synthesis of ureas is described. Boc-protected amines can be
      transformed into nonsymmetrical and symmetrical disubstituted and trisubstituted
      ureas utilizing 2-chloropyridine and trifluoromethanesulfonyl anhydride for the
      in situ generation of an isocyanate, which reacts with an amine. A variety of
      amines can be employed successfully, leading to high yields of isolated ureas. 

PMID- 24750029
TI  - Short-term clinical of peel-off facial mask moisturizers.
AB  - OBJECTIVE: This study aimed to compare the efficacy of a peel-off facial mask
      based on polyvinyl alcohol (PVA) with an oil-in-water (o/w) emulsion and the
      effect of a soybean extract fermented by Bifidobacterium animale incorporated in
      those formulations (5% w/w). METHODS: The formulations were submitted to
      randomized clinical studies in volunteers to evaluate the measurement effects as
      (a) tensor by Cutometer(r) , (b) moisturizing by Corneometer(r) and
      transepidermal water loss (TEWL) by Tewameter(r) . These effects were determined
      in a short-term study (3 h) in a controlled-temperature room. RESULTS: The tensor
      effect and TEWL values indicated no significant difference between the use of
      facial mask and emulsion. On the other hand, the moisturizing effect of the
      facial mask on the stratum corneum was more significant than that of the emulsion
      according to Corneometer(r) measurements. Biometric cutaneous evaluation of peel
      off facial masks (short-term study) showed that the masks promoted moisturizing
      effect of the stratum corneum more effectively than the oil-in-water emulsions.
      Thus, the facial masks were more efficient than emulsions in relation to
      moisturizing effects, but this efficiency is not related to the presence of
      fermented soybean extract. CONCLUSION: The results indicated that peel-off facial
      masks increase skin hydration in a process related to the occlusive effect.

PMID- 24750030
TI  - Validation of the Chinese version of Differentiation of Self Inventory (C-DSI).
AB  - Although the need to develop objective assessment tools in different cultures is
      well-recognized, there is a severe lack of objective measures about emotional
      functioning in the Chinese context. This project conducted three studies to
      validate the Chinese version of the Differentiation of Self Inventory (DSI).
      Study 1 looked at the factor structure, internal consistency, concurrent
      validity, and construct validity of the C-DSI. Study 2 examined the test-retest
      reliability of the C-DSI. Study 3 tested the discriminant validity of the C-DSI
      in a clinical sample and in a nonclinical sample and examined its correlations
      with the General Contentment Scale (GCS). The study results suggested that the C
      DSI possesses good psychometric properties. Findings also indicated implications
      of divergent cultures and hinted at treatment implications--taking the familistic
      orientation and the Chinese meaning of self into consideration to understand the
      differentiation of self in the Chinese culture context.

PMID- 24750031
TI  - Asexuality: A Multidimensional Approach.
AB  - While lack of sexual attraction, lack of sexual behavior, and self-identification
      as asexual have been used as criteria to define asexuality, it is not known how
      much they overlap in describing the same group of people. This study aimed to
      assess how many individuals could be identified as asexual based on each of these
      criteria and on combinations of these criteria. Participants were recruited
      through the Asexuality Visibility and Education Network, social media, and posts
      on several health- and lifestyle-related websites. In total, 566 participants
      between 18 and 72 years old (M = 27.86, SD = 10.53) completed an online survey
      (24% male, 68.9% female, 7.1% "other"). Based on self-identification or lack of
      sexual attraction, 71.3% and 69.2%, respectively, of participants were
      categorized as asexual, while based on lack of sexual behavior only 48.5% were
      categorized as asexual. Gender differences were found only for those participants
      who indicated that they did not experience sexual attraction, with more women
      (72.8%) than men (58.8%) indicating a lack of sexual attraction. Given that self
      identification as asexual implies familiarity with the term asexual, we argue for
      the use of lack of sexual attraction as the primary criterion to define
      asexuality. 

PMID- 24750032
TI  - Selective detection of dopamine combining multilayers of conducting polymers with
      gold nanoparticles.
AB  - Electrodes based on the combination of three-layered films formed by two
      different conducting polymers and gold nanoparticles have been developed for the
      selective voltammetric determination of dopamine in mixtures with ascorbic acid
      and uric acid and human urine samples with real interferents. Voltammetric
      studies of solution mixtures indicate that electrodes formed by alternated layers
      of poly(3,4-ethylenedioxithiophene) (internal and external layer) and poly(N
      methylpyrrole) (intermediate layer) show the best performance in terms of
      sensitivity and resolution. Furthermore, the sensitivity of such three-layered
      electrodes increases only slightly after coating its surface with gold
      nanoparticles (AuNPs), indicating that the catalytic effect typically played by
      AuNPs in the oxidation of dopamine is less effective in this case.
      Electrochemical pretreatments based on the application of consecutive oxidation
      reduction cycles to electrodes before the detection process have been found to
      improve the selectivity without altering the sensitivity. On the other hand, the
      flux of dopamine to the three-layered surface increases linearly with the scan
      rate. The detection limit for these electrodes is around 10 MUM DA in mixtures
      with uric acid, ascorbic acid, and cetaminophen, decreasing to 2-3 MUM in the
      absence of such interferents. The utility of three-layered electrodes as sensors
      has also been demonstrated by determining DA in human samples with real
      interferents. 

PMID- 24750033
TI  - Endogenous polyamines reduce the toxicity of soluble abeta peptide aggregates
      associated with Alzheimer's disease.
AB  - Polyamines promote the formation of the Abeta peptide amyloid fibers that are a
      hallmark of Alzheimer's disease. Here we show that polyamines interact with
      nonaggregated Abeta peptides, thereby reducing the peptide's hydrophobic surface.
      We characterized the associated conformational change through NMR titrations and
      molecular dynamics simulations. We found that even low concentrations of
      spermine, sperimidine, and putrescine fully protected SH-SY5Y (a neuronal cell
      model) against the most toxic conformational species of Abeta, even at an Abeta
      oligomer concentration that would otherwise kill half of the cells or even more.
      These observations lead us to conclude that polyamines interfere with the more
      toxic prefibrillar conformations and might protect cells by promoting the
      structural transition of Abeta toward its less toxic fibrillar state that we
      reported previously. Since polyamines are present in brain fluid at the
      concentrations where we observed all these effects, their activity needs to be
      taken into account in understanding the molecular processes related to the
      development of Alzheimer's disease. 

PMID- 24750034
TI  - Allergens on desktop surfaces in preschools and elementary schools of urban
      children with asthma.
AB  - Desktop dust has been studied as a source of food allergen, but not as a source
      of potential aeroallergen exposure. Thirty-six wiped samples from desktop
      surfaces were collected from preschools and schools. Samples were analyzed for
      detectable levels of common aeroallergens including Alternaria, cockroach, dog,
      dust mite, cat, mouse, and rat allergens by immunoassay. Mouse allergen was the
      most prevalent, detectable in 97.2% of samples. Cat allergen was detectable in
      80.6% of samples, and dog allergen was detectable in 77.8% of samples. Other
      allergens were not as prevalent. Mouse was the only allergen that was highly
      correlated with settled floor dust collected from the same rooms (r = 0.721, P <
      0.001). This is the first study to detect aeroallergens on desktop surfaces by
      using moist wipes. Allergens for mouse, cat, and dog were highly detectable in
      wipes with mouse desktop surface levels correlating with levels in vacuumed floor
      dust. 

PMID- 24750036
TI  - Live-cell imaging of phosphatidic acid dynamics in pollen tubes visualized by
      Spo20p-derived biosensor.
AB  - Although phosphatidic acid (PA) is structurally the simplest membrane
      phospholipid, it has been implicated in the regulation of many cellular events,
      including cytoskeletal dynamics, membrane trafficking and stress responses. Plant
      PA shows rapid turnover but the information about its spatio-temporal
      distribution in plant cells is missing. Here we demonstrate the use of a lipid
      biosensor that enables us to monitor PA dynamics in plant cells. The biosensor
      consists of a PA-binding domain of yeast SNARE Spo20p fused to fluorescent
      proteins. Live-cell imaging of PA dynamics in transiently transformed tobacco
      (Nicotiana tabacum) pollen tubes was performed using confocal laser scanning
      microscopy. In growing pollen tubes, PA shows distinct annulus-like fluorescence
      pattern in the plasma membrane behind the extreme tip. Coexpression studies with
      markers for other plasmalemma signaling lipids phosphatidylinositol 4,5
      bisphosphate and diacylglycerol revealed limited colocalization at the shoulders
      of the apex. PA distribution and concentrations show distinct responses to
      various lipid signaling inhibitors. Fluorescence recovery after photobleaching
      (FRAP) analysis suggests high PA turnover in the plasma membrane. Our data show
      that a biosensor based on the Spo20p-PA binding domain is suitable for live-cell
      imaging of PA also in plant cells. In tobacco pollen tubes, distinct subapical PA
      maximum corroborates its involvement in the regulation of endocytosis and actin
      dynamics. 

PMID- 24750035
TI  - Crucial role of androgen receptor in vascular H2S biosynthesis induced by
      testosterone.
AB  - BACKGROUND AND PURPOSE: Hydrogen sulphide (H2S) is a gaseous mediator strongly
      involved in cardiovascular homeostasis, where it provokes vasodilatation. Having
      previously shown that H2 S contributes to testosterone-induced vasorelaxation,
      here we aim to uncover the mechanisms underlying this effect. EXPERIMENTAL
      APPROACH: H2 S biosynthesis was evaluated in rat isolated aortic rings following
      androgen receptor (NR3C4) stimulation. Co-immunoprecipitation and surface plasmon
      resonance analysis were performed to investigate mechanisms involved in NR3C4
      activation. KEY RESULTS: Pretreatment with NR3C4 antagonist nilutamide prevented
      testosterone-induced increase in H2S and reduced its vasodilator effect. Androgen
      agonist mesterolone also increased H2S and induced vasodilatation; effects
      attenuated by the selective cystathionine-gamma lyase (CSE) inhibitor
      propargylglycine. The NR3C4-multicomplex-derived heat shock protein 90 (hsp90)
      was also involved in this effect; its specific inhibitor geldanamycin strongly
      reduced testosterone-induced H2S production. Neither progesterone nor 17-beta
      oestradiol induced H2S release. Furthermore, we demonstrated that CSE, the main
      vascular H2S-synthesizing enzyme, is physically associated with the NR3C4/hsp90
      complex and the generation of such a ternary system represents a key event
      leading to CSE activation. Finally, H2S levels in human blood collected from male
      healthy volunteers were higher than those in female samples. CONCLUSIONS AND
      IMPLICATIONS: We demonstrated that selective activation of the NR3C4 is essential
      for H2S biosynthesis within vascular tissue, and this event is based on the
      formation of a ternary complex between cystathionine-gamma lyase, NR3C4and hsp90.
      This novel molecular mechanism operating in the vasculature, corroborated by
      higher H2S levels in males, suggests that the L-cysteine/CSE/H2S pathway may be
      preferentially activated in males leading to gender-specific H2S biosynthesis.

PMID- 24750037
TI  - The impact of storage temperature on the morphology, viability, cell number and
      metabolism of cultured human conjunctival epithelium.
AB  - PURPOSE: To evaluate the effect of storage temperature on the morphology,
      viability, cell number and metabolism of cultured human conjunctival epithelial
      cells (HCjEs). MATERIALS AND METHODS: Three-day cultured HCjEs were stored at
      nine different temperatures between 4  degrees C and 37  degrees C for four and
      seven days. Phenotype was assessed by immunofluorescence microscopy, morphology
      by scanning electron microscopy, viability and cell number by a microplate
      fluorometer and glucose metabolism by a blood gas analyzer. RESULTS: Cultured
      cells not subjected to storage expressed the conjunctival cytokeratins 7 and 19
      and the proliferation marker proliferating cell nuclear antigen. Cell morphology
      was best maintained following four-day storage between 12  degrees C and 28 
      degrees C and following 12  degrees C storage after seven days. Assessed by
      propidium iodide uptake, the percentage of viable cells after four-day storage
      was maintained only between 12  degrees C and 28  degrees C, whereas it had
      decreased in all other groups (p < 0.05; n = 4). After seven days this percentage
      was maintained in the 12  degrees C group, but it had decreased in all other
      groups, compared to the control (p < 0.05; n = 4). The total number of cells
      remaining in the cultures after four-day storage, compared to the control, had
      declined in all groups (p < 0.05; n = 4), except 12  degrees C and 20  degrees C
      groups. Following seven days this number had decreased in all groups (p < 0.01; n
      = 4), except 12  degrees C storage. Four-day storage at 12  degrees C
      demonstrated superior preservation of the number of calcein-stained viable cells
      (p < 0.05) and the least accumulation of ethidium homodimer 1-stained dead cells
      (p < 0.001), compared to storage at 4  degrees C and 24  degrees C (n = 6). The
      total metabolism of glucose to lactate after four-day storage was higher in the
      24  degrees C group compared to 4  degrees C and 12  degrees C groups, as well as
      the control (p < 0.001; n = 3). CONCLUSIONS: Storage at 12  degrees C appears
      optimal for preserving the morphology, viability and total cell number in stored
      HCjE cultures. The superior cell preservation at 12  degrees C may be related to
      temperature-associated effects on cell metabolism.

PMID- 24750038
TI  - The effect of audible alarms on anaesthesiologists' response times to adverse
      events in a simulated anaesthesia environment: a randomised trial.
AB  - Alarms are ubiquitous in anaesthetic practice, but their net effect on
      anaesthesiologists' performance and patient safety is debated. In this study, 27
      anaesthesiologists performed two simulation sessions in random order; one session
      was programmed to include an alarm condition, with a standard, frequent, clearly
      audible alarm sound. During these sessions, adverse events were simulated and
      anaesthesiologists' response times to these events were recorded. Perceived
      workload was assessed with the NASA Task Load Index. Response times to adverse
      events and perceived workload were similar in both groups. Pooled response times
      to atrial fibrillation and desaturation were fast, with a median (range [IQR]) of
      8 (4-14 [1-41]) s and 9 (6-16 [1-44]) s, respectively. Pooled response times to
      an ST segment elevation on the ECG and an obstructed intravenous line were
      significantly slower, with median (IQR[range]) times of 34 (21-76[4-300]) s and
      227 (95-399 [2-600]) s, respectively (p < 0.001). This study shows that in a
      simulated anaesthesia environment, response times to adverse events are similar
      in the absence or presence of an audible alarm, and that response times to
      various critical events differ.

PMID- 24750040
TI  - Lingappa et al. reply.

PMID- 24750039
TI  - Predictors of motivation to change in mandated college students following a
      referral incident.
AB  - The purpose of present study was to understand factors that are related to a
      desire or motivation to change (MTC) alcohol use in a sample of college students
      mandated to receive an alcohol intervention. We examined characteristics of and
      reactions to the referral event, typical alcohol use involvement, and alcohol
      beliefs about the perceived importance of drinking in college assessed by the
      College Life Alcohol Salience Scale (CLASS; Osberg et al., 2010) as predictors of
      MTC following referral to an alcohol intervention. College students (N = 932) who
      presented for a mandatory alcohol intervention following a referral event (e.g.,
      citation for underage drinking, medical attention for an alcohol-related
      incident, or driving under the influence) completed an assessment prior to
      receiving an alcohol intervention. Higher perceived aversiveness of the referral
      event and higher personal responsibility one felt for the occurrence of the event
      were positively related to higher MTC. Although alcohol beliefs about the role of
      drinking in college were not significantly related to either event aversiveness
      or responsibility, it was negatively related to MTC even after controlling for
      alcohol use involvement variables. Alcohol beliefs about the role of drinking in
      college represent an important construct that is related to increased alcohol use
      and alcohol-related problems and decreased MTC in a sample of college students.
      Interventions aimed at reducing alcohol beliefs about the role of drinking in
      college may be an effective strategy to reduce alcohol use and alcohol-related
      problems by college students.

PMID- 24750041
TI  - Crystal growth, structural, electrical, and magnetic properties of mixed-valent
      compounds YbOs2Al10 and LuOs2Al10.
AB  - Single crystals of YbOs2Al10 and LuOs2Al10 were grown for the first time using an
      aluminum self-flux method. The compounds crystallized into a cagelike structure
      in space group Cmcm, similar to the prototype compound YbFe2Al10. YbOs2Al10
      exhibited a mixed-valent nature, as determined by magnetic susceptibility
      measurements over a wide temperature range from 2 to 900 K, in which the inter
      configuration-fluctuation model revealed a broad peak around 400 K. In contrast,
      LuOs2Al10 displayed Pauli-like paramagnetic behavior over the same temperature
      range. Both compounds were metallic in nature between 2 and 300 K. The electronic
      specific heat coefficient of 21.3(2) mJ mol(-1) K(-2) for YbOs2Al10 was
      determined to be larger than that for LuOs2Al10 [8.9(1) mJ mol(-1) K(-2)],
      reflecting the mixed-valent nature of the former. First-principles calculations
      predicted the presence of a mixed-valent state in YbOs2Al10, in agreement with
      the experimental observations. The novel compound YbOs2Al10 elucidates the
      evolution of the mixed-valent nature of the Yb-based ternary transition metal
      aluminides from the 3d to 5d elements. 

PMID- 24750042
TI  - Clinical aspects of headache in HIV.
AB  - BACKGROUND: Headaches are commonly seen in those patients with human
      immunodeficiency virus (HIV) and are the most common form of pain reported among
      HIV patients. There have been relatively few studies attempting to determine the
      rates and phenotypes of the headaches that occur in patients with HIV.
      DISCUSSION: Patients with HIV are susceptible to a much broader array of
      secondary headache causes, sometimes with atypical manifestations due to a
      dampened inflammatory response. The investigation of a headache in the HIV
      patient should be thorough and focused on making sure that secondary and HIV
      specific causes are either ruled out or treated if present. CONCLUSION: An
      effective treatment plan should incorporate the use of appropriate
      pharmacological agents along with the integration of non-pharmacological
      therapies, such as relaxation and lifestyle regulation. When treating for
      headaches in patients with HIV, it is important to keep in mind comorbidities and
      other medications, especially combination antiretroviral therapy. For those with
      complicated headache histories, referral to a specialized headache center may be
      appropriate.

PMID- 24750043
TI  - The life cycle of a virus: the infectious disease narrative of NDM-1.
AB  - This study is a report of a two-part content analysis of domestic and
      international print news reports (over a 3-year period) that examined how the
      nature of the New Delhi Metallo-beta-lactamase-1 (NDM-1) virus and the severity
      of the threat were conveyed to global audiences. In particular, the authors
      focused on the ongoing crisis narrative of NDM-1 and the potentially negative
      outcomes of international communication warning and false alarm systems regarding
      global health threats. The results indicated key differences in media narratives
      between the initial 2011 outbreak and the 2012 postcrisis state. The authors
      examine the theoretical and practical implications of the findings as well as key
      limitations and directions for future research. 

PMID- 24750044
TI  - Tissue-engineered tracheal reconstruction using three-dimensionally printed
      artificial tracheal graft: preliminary report.
AB  - Three-dimensional printing has come into the spotlight in the realm of tissue
      engineering. We intended to evaluate the plausibility of 3D-printed (3DP)
      scaffold coated with mesenchymal stem cells (MSCs) seeded in fibrin for the
      repair of partial tracheal defects. MSCs from rabbit bone marrow were expanded
      and cultured. A half-pipe-shaped 3DP polycaprolactone scaffold was coated with
      the MSCs seeded in fibrin. The half-pipe tracheal graft was implanted on a 10 *
      10-mm artificial tracheal defect in four rabbits. Four and eight weeks after the
      operation, the reconstructed sites were evaluated bronchoscopically,
      radiologically, histologically, and functionally. None of the four rabbits showed
      any sign of respiratory distress. Endoscopic examination and computed tomography
      showed successful reconstruction of trachea without any collapse or blockage. The
      replaced tracheas were completely covered with regenerated respiratory mucosa.
      Histologic analysis showed that the implanted 3DP tracheal grafts were
      successfully integrated with the adjacent trachea without disruption or
      granulation tissue formation. Neo-cartilage formation inside the implanted graft
      was sufficient to maintain the patency of the reconstructed trachea. Scanning
      electron microscope examination confirmed the regeneration of the cilia, and
      beating frequency of regenerated cilia was not different from those of the normal
      adjacent mucosa. The shape and function of reconstructed trachea using 3DP
      scaffold coated with MSCs seeded in fibrin were restored successfully without any
      graft rejection. 

PMID- 24750045
TI  - Novel genetic targets in endometrial cancer.
AB  - Worldwide, ~ 74,000 women die from endometrial cancer each year. Understanding
      the somatic genomic alterations that drive endometrial tumorigenesis may provide
      new opportunities to identify targeted therapies for specific subsets of
      patients. Since 2012, the use of next-generation sequencing to decode the
      mutational landscape of endometrial tumors has not only confirmed prior knowledge
      of established genetic targets for serous and endometrioid endometrial carcinomas
      (ECs), but has also uncovered novel significantly mutated genes, referred to
      herein as novel genetic targets, which represent candidate cancer genes in these
      tumors. This editorial summarizes the novel genetic targets that have been
      identified in serous and endometrioid ECs, according to their unifying functional
      characteristics. An expert opinion section comments on remaining knowledge gaps
      that will undoubtedly be filled in future genomic studies of endometrial cancer. 

PMID- 24750046
TI  - The family context of relational aggression in "difficult to treat" female
      juvenile offenders.
AB  - Female juvenile offenders often engage in socially aggressive behaviors that make
      them more difficult to treat than male juvenile offenders. This social (i.e.,
      relational) aggression may be developed or maintained through transactions with
      family members. To investigate this issue, we measured relational aggression in
      the family interactions of 140 adolescents divided by gender and offender status
      into four equal-sized groups (female juvenile offenders, male juvenile offenders,
      female nonoffenders, and male nonoffenders). Adolescents and caregivers completed
      a family discussion task, and raters coded relationally aggressive behaviors at
      the dyadic level. Results showed that female juvenile offenders and their mothers
      directed more relational aggression toward each other than did mother-adolescent
      dyads in the other groups. Implications of these results for treatment and
      research are discussed. 

PMID- 24750047
TI  - Transition metal-catalyzed cascade cyclization of aryldiynes to halogenated
      benzo[b]naphtho[2,1-d]thiophene derivatives.
AB  - Treatment of 2-(2-(2-(2-substituted ethynyl)phenyl)ethynyl)thioanisoles (1) with
      5 mol % of Ph3PAuCl/AgSbF6 and 2 equiv of NIS at refluxing CH2Cl2 gave iodo
      substituted benzo[b]naphtho[2,1-d]thiophene (6) in good yields. Chloro- and bromo
      substituted benzo[b]naphtho[2,1-d]thiophene derivatives (8 and 9) were also
      generated by treating compound 1 with 5 mol % of PdX2 and 3 equiv of CuX2 at
      refluxing THF. 

PMID- 24750048
TI  - Yashada bhasma (Zinc calx) and Tankana (Borax) inhibit Propionibacterium acne and
      suppresses acne induced inflammation in vitro.
AB  - OBJECTIVE: Yashada bhasma (YB) and Tankana (TA) are well characterized minerals
      used in traditional medicine for the treatment of various skin ailments. Yashada
      bhasma and TA are a unique preparation of zinc and borax, respectively. The study
      was conducted to evaluate the in vitro inhibitory effect of YB, TA and its
      combination (YBTA) on Propionibacterium acne growth and P. acne-induced
      inflammation. METHODS: The minerals were tested for anti-P. acne activity by disc
      diffusion and broth microdilution methods. The effect of these minerals on P.
      acne induced TNF-alpha and IL-8 production and gene expression were studied in
      THP-1 cells. In vitro toxicity was tested on human keratinocytes (HaCaT) and
      mouse embryonic fibroblasts (NIH3T3) using MTT assay. RESULTS: The minimum
      inhibitory concentrations (MIC values) for YB, TA and YBTA against P. acne were
      0.1 +/- 0.2, 1.9 +/- 0.5 and 0.3 +/- 0.5 mg mL(-1) , respectively. YB, TA and
      YBTA inhibited TNFalpha by 57.57%, 59.09% and 68.93% and IL-8 production by
      48.76%, 47.92% and 51.13% in P. acne-stimulated THP-1 cells, respectively. The
      CTC50 values on HaCaT and NIH3T3 was 17.44 +/- 0.5 and 16.37 +/- 0.2 MUg mL(-1)
      for YB, 1023.03 +/- 4.0 and 1286.17 +/- 4.4 MUg mL(-1) for TA and 89.12 +/- 2.3
      and 111.58 +/- 3.5 MUg mL(-1) for YBTA, respectively. CONCLUSION: The present
      study revealed the inhibitory effect of YB, TA and YBTA on P. acne growth and
      inflammation. Clinical studies have suggested the anti-acne benefits of
      formulations containing YB and TA. The findings obtained from the present in
      vitro studies provide evidence to support the mechanism of anti-acne properties
      of YB and TA.

PMID- 24750049
TI  - IPA3 non-specifically enhances phosphorylation of several proteins in human
      platelets.
AB  - PAK (p21-Activation kinase), a serine-threonine protein kinase contains an
      autoinhibitory domain that suppresses the catalytic activity of its kinase
      domain. This autoregulatory domain found within PAK kinase provides a unique
      target for chemical inhibitors. IPA3, a small molecule allosteric inhibitor of
      PAK activation, binds covalently to the PAK regulatory domain and prevents
      binding to its upstream activators. IPA3 has been used in various cells including
      platelets to evaluate the role of PAK in signaling. In a recent study, PAK
      functions in platelet aggregation and lamellipodia formation were evaluated using
      IPA3 as the PAK inhibitor. Herein, we investigated the specificity and
      selectivity of IPA3 as a PAK inhibitor in the human platelets. Stimulation of
      platelets pretreated with IPA3 using a PAR-4 or GPV1 agonist resulted in a
      concentration-dependent inhibition of aggregation, as was suggested by earlier
      studies. Interestingly, we found that incubation of washed human platelets with
      IPA3 lead to a non-specific increase in phosphorylation of several proteins in
      absence of any agonist. However, this phosphorylation is not sufficient for
      aggregation of platelets by IPA3. In summary, we demonstrate that IPA3 by itself
      can phosphorylate several proteins in human platelets and thus its use is not an
      appropriate strategy for investigating PAK function in platelets. 

PMID- 24750050
TI  - Management of the acute painful crisis in sickle cell disease- a re-evaluation of
      the use of opioids in adult patients.
AB  - Management of the acute painful crisis (APC) of sickle cell disease (SCD) remains
      unsatisfactory despite advances in the understanding and management of acute pain
      in other clinical settings. One reason for this is an unsophisticated approach to
      the use of opioid analgesics for pain management. This applies to haematologists
      who are responsible for developing acute sickle pain management protocols for
      their patients, and to health care staff in the acute care setting. The objective
      of this article is to evaluate the evidence for use of opioids in APC management.
      We have highlighted the possibilities for improving management by using
      alternatives to morphine, and intranasal (IN) or transmucosal routes of
      administration for rapid onset of analgesia in the emergency department (ED). We
      suggest how experience gained in managing acute sickle pain in children could be
      extrapolated to adolescents and young adults. We have also questioned whether
      patients given strong opioids in the acute setting are being safely monitored and
      what resources are required to ensure efficacy, safety and patient satisfaction.
      We also identify aspects of care where there are significant differences of
      opinion, which require further study by randomized controlled trial. 

PMID- 24750051
TI  - Stem cell science should be tweeted.

PMID- 24750052
TI  - Stem cell-based therapies for multiple sclerosis: recent advances in animal
      models and human clinical trials.

PMID- 24750053
TI  - STAP cells: stress-induced stem cells?

PMID- 24750055
TI  - Highlights from the latest articles in regenerative medicine.

PMID- 24750056
TI  - World Conference on Regenerative Medicine.

PMID- 24750057
TI  - Altered hMSC functional characteristics in short-term culture and when placed in
      low oxygen environments: implications for cell retention at physiologic sites.
AB  - BACKGROUND: It is very difficult to conserve critical cell characteristics during
      expansion in culture, particularly those of adult mesenchymal stromal cells
      (MSCs), whose characteristics can change rapidly even within a short period of
      expansion. AIM: In this study our aim was to measure cell characteristics that
      are critical for retention at the injury site after therapeutic delivery. Cells
      were cultured under conditions typical of current standard best practice. The
      impact of passage number was assessed and assays were performed in low oxygen
      (2%) as an in vitro model of physiologic oxygen tension at injury sites. The
      effect of chemokine preconditioning with SDF1 was also assessed. MATERIALS &
      METHODS: Bone marrow mononuclear cells from patients recruited to the REGENERATE
      Phase II clinical trials, along with MSCs from healthy volunteers subjected to a
      short period of expansion, were assessed for attachment and migration ability.
      Using MSCs from healthy donors, the effect of reduced oxygen was also assessed.
      RESULTS: Short-term expansion resulted in increased cell attachment but decreased
      rate of migration, whereas attachment and migration of patient-derived bone
      marrow mononuclear cells was highly heterogeneous. Reduced oxygen impaired MSC
      attachment but not migration. Finally, SDF1 did not improve any of the responses.
      CONCLUSION: The basic functional responses of MSCs required for retention and
      engraftment alter rapidly even over a relatively short expansion period. This
      needs careful consideration when expanding cells to achieve clinical quantities
      for therapy.

PMID- 24750058
TI  - Challenges in the development of a reference standard and potency assay for the
      clinical production of RAFT tissue equivalents for the cornea.
AB  - AIM: To develop a reference standard and potency assay for Real Architecture For
      3D Tissues (RAFT) tissue equivalents intended for use in limbal epithelial stem
      cell (LESC) therapy for the cornea. METHODS: RAFT, a cell-seeded plastic
      compressed collagen construct with LESCs cultured on the surface, was
      manufactured with the goal of achieving GMP compliance. RAFTs were tested for
      reproducibility of manufacture (reference standard) and subsequently wounded and
      monitored for re-epithelialization (potency assay). RESULTS: RAFT tissue
      equivalents produced with cells from different biological donors were capable of
      supporting multilayered epithelium in culture. The potency assay demonstrated re
      epithelialization following wounding, indicating the potential efficacy of RAFT
      constructs. CONCLUSION: We have presented our attempts at creating a reference
      standard and potency assay for the clinical manufacture of RAFT for the treatment
      of LESC deficiency. However, it remains challenging for adult stem cell therapies
      (including LESC therapy) to fully meet regulatory requirements when dealing with
      a limited source of autologous cells with inherent biological variation between
      donors.

PMID- 24750059
TI  - Regenerative medicine applications in combat casualty care.
AB  - The purpose of this report is to describe regenerative medicine applications in
      the management of complex injuries sustained by service members injured in
      support of the wars in Afghanistan and Iraq. Improvements in body armor,
      resuscitative techniques and faster transport have translated into increased
      patient survivability and more complex wounds. Combat-related blast injuries have
      resulted in multiple extremity injuries, significant tissue loss and amputations.
      Due to the limited availability and morbidity associated with autologous tissue
      donor sites, the introduction of regenerative medicine has been critical in
      managing war extremity injuries with composite massive tissue loss. Through case
      reports and clinical images, this report reviews the application of regenerative
      medicine modalities employed to manage combat-related injuries. It illustrates
      that the novel use of hybrid reconstructions combining traditional and
      regenerative medicine approaches are an effective tool in managing wounds.
      Lessons learned can be adapted to civilian care. 

PMID- 24750060
TI  - Gene patents, patenting life and the impact of court rulings on US stem cell
      patents and research.
AB  - In June 2013, the US Supreme Court ruled that naturally occurring genes were
      unpatentable in the case Association for Molecular Pathology v. Myriad Genetics.
      Up until this decision, Myriad Genetics was the only company in the USA that
      could legally conduct diagnostic testing for BRCA1 and 2, genes that are linked
      to familial breast and ovarian cancer. The court case and rulings garnered
      discussion in public about patenting biological materials. This paper will
      describe the progression of the Myriad Genetics case, similar US rulings and
      biological intellectual property policies. In addition, it will discuss the
      impact of the case on biological patents - specifically those for human embryonic
      stem cells. 

PMID- 24750061
TI  - Progress towards cell-based burn wound treatments.
AB  - Cell therapy as part of the concept of regenerative medicine represents an
      upcoming platform technology. Although cultured epidermal cells have been used in
      burn treatment for decades, new developments have renewed the interest in this
      type of treatment. Whereas early results were hampered by long culture times in
      order to produce confluent sheets of keratinocytes, undifferentiated
      proliferating cells can nowadays be applied on burns with different application
      techniques. The application of cells on carriers has improved early as well as
      long-term results in experimental settings. The results of several commercially
      available epidermal substitutes for burn wound treatment are reviewed in this
      article. These data clearly demonstrate a lack of randomized comparative trials
      and application of measurable outcome parameters. Experimental research in
      culture systems and animal models has demonstrated new developments and proof of
      concepts of further improvements in epidermal coverage. These include
      combinations of epidermal cells and mesenchymal stem cells, and the guidance of
      both material and cell interactions towards regeneration of skin appendages as
      well as vascular and nerve structures. 

PMID- 24750062
TI  - Stem cells for osteodegenerative diseases: current studies and future outlook.
AB  - As the worldwide population grows and life expectancies continue to increase,
      degenerative diseases of the bones, muscles, and connective tissue are a growing
      problem for society. Current therapies for osteodegenerative disorders such as
      hormone replacement therapies, calcium/vitamin D supplements and oral
      bisphosphonates are often inadequate to stop degeneration and/or have serious
      negative side effects. Thus, there is an urgent need in the medical community for
      more effective and safer treatments. Stem cell therapies for osteodegenerative
      disorders have been rigorously explored over the last decade and are yielding
      some promising results in animal models and clinical trials. Although much work
      still needs to be done to ensure the safety and efficacy of these therapies, stem
      cells represent a new frontier of exciting possibilities for bone and cartilage
      regeneration. 

PMID- 24750063
TI  - The strategy and method in modulating finger regeneration.
AB  - The tip of the human finger can regenerate if the amputation is distal to the
      nail bed, usually in young children. Studies in regeneration of rodent digits
      have shown that regeneration occurs if the amputation is distal to the mid-third
      phalanx for certain ages. The digit contains many different components, such as
      muscle, tendon, bone, skin, nerves and blood vessels, which must all be regrown
      in the proper location in order to restore functionality. The mechanism behind
      the complex healing/regeneration processes is still under investigation; however,
      improvements in injured finger regeneration have been gradually developing in
      animal models over the past few years. This review discusses a few strategies and
      methods to possibly enhance digit regeneration beyond current natural limits,
      focusing on aspects including scarless wound healing, cell-based treatments,
      tissue engineering and electrical stimulation. 

PMID- 24750064
TI  - Contribution of socio-economic status on the prevalence of cerebral palsy: a
      systematic search and review.
AB  - AIM: The association between socio-economic status (SES) and cerebral palsy (CP)
      remains controversial. Preterm birth, low birthweight, and postnatal injuries are
      accepted mediating risk factors for CP, but the question remains whether SES
      confers additional risk. The aim of this study was to analyse existing knowledge
      on the relationship between SES and the risk of CP. METHOD: We conducted a
      systematic search and review of potentially relevant research relating to SES and
      CP published from 1980 to 2012. Heterogeneity between studies did not allow for
      data aggregation or meta-analysis; therefore, a narrative review was used to
      summarize the findings. RESULTS: Twelve studies were included in the systematic
      review. Of these, eight found low SES to be a risk factor for increased CP
      prevalence. Three studies detected statistically significant associations even
      after controlling for birthweight and gestational age as variables. Two of these
      studies also accounted for additional confounding variables (multiple births and
      timing of CP acquisition) and continued to detect contributory effects of SES.
      Linear negative correlations between CP prevalence and SES were shown by three
      studies. INTERPRETATION: Evidence suggests that the effect of SES on CP
      prevalence goes beyond that of the mediating factors preterm birth, low
      birthweight, and postnatal trauma. These associations were seen in area-based
      and, to a lesser extent, individual measures of SES. A better understanding of
      mediating factors is imperative in developing targeted public health intervention
      programmes to reduce the prevalence of CP.

PMID- 24750065
TI  - Electroresponsive aqueous silk protein as "smart" mechanical damping fluid.
AB  - Here we demonstrate the effectiveness of an electroresponsive aqueous silk
      protein polymer as a smart mechanical damping fluid. The aqueous polymer solution
      is liquid under ambient conditions, but is reversibly converted into a gel once
      subjected to an electric current, thereby increasing or decreasing in viscosity.
      This nontoxic, biodegradable, reversible, edible fluid also bonds to device
      surfaces and is demonstrated to reduce friction and provide striking wear
      protection. The friction and mechanical damping coefficients are shown to
      modulate with electric field exposure time and/or intensity. Damping coefficient
      can be modulated electrically, and then preserved without continued power for
      longer time scales than conventional "smart" fluid dampers. 

PMID- 24750066
TI  - Bulky quaternary alkylammonium counterions enhance the nanodispersibility of
      2,2,6,6-tetramethylpiperidine-1-oxyl-oxidized cellulose in diverse solvents.
AB  - The degree of nanodispersion of cellulose in diverse solvents is a significant
      primary criterion for the preparation of bulk nanocelluloses and nanocellulose
      containing composites. Here, high degrees of nanodispersion of fibrous 2,2,6,6
      tetramethylpiperidine-1-oxyl-oxidized cellulose (TOC) were achieved in various
      solvents by efficiently incorporating quaternary alkylammoniums (QAs) as
      counterions of TOC carboxyl groups via simple ion-exchange treatment in water.
      Tetramethyl-, tetraethyl-, tetra-n-propyl-, and tetra-n-butylammoniums were used
      as the QAs. The TOC-QAs were converted to TOC nanofibrils (TOCN-QAs) with a high
      nanofibrillation yield via mechanical disintegration in not only water but also
      methanol and other organic solvents after solvent-exchange treatment. Fourier
      transform infrared spectra of cast TOCN-QA films and the electric conductivities
      of the TOCN-QA dispersions indicated that the TOCNs-QAs were dispersed primarily
      through dissociation of the bulky QA carboxylate groups. Moreover, the TOC-QAs
      were nanodispersible in water even after being oven dried at 105  degrees C,
      which is advantageous for their practical application. 

PMID- 24750067
TI  - Expression of neurodegenerative disease-related proteins and caspase-3 in
      glioneuronal tumours.
AB  - AIMS: Recent evidence supports the activation of mechanisms underlying cellular
      ageing and neurodegeneration in developmental lesions associated with epilepsy.
      The present study examined the ongoing cell injury and vulnerability to neuronal
      degeneration in glioneuronal tumours (GNT). METHODS: We evaluated a series of GNT
      (n = 31 gangliogliomas, GG and n = 30 dysembryoplastic neuroepithelial tumours,
      DNT). Sections were processed for immunohistochemistry using markers for the
      evaluation of caspase-3 and neurodegeneration-related proteins/pathways and their
      expression was correlated with the tumour features and the clinical history of
      epilepsy. RESULTS: Both GG and DNT specimens contained caspase-3-positive cells.
      In GG, expression of activated caspase-3 was negatively correlated the with the
      BRAF V600E mutation status. We also observed an abnormal expression of death
      receptor-6 and beta-amyloid precursor protein (APP). Moreover, dysplastic
      neurones expressed p62, phosphorylated (p)TDP43 and pTau. Double labelling
      experiments showed colocalization of phosphorylated S6 (marker of mammalian
      target of rapamycin, mTOR, pathway activation) with pTau and p62. In GG, neuronal
      p62 expression was positively correlated with pS6. The immunoreactivity score
      (IRS) of caspase-3, APP, DR6, p62 and pTDP43 were found to be significantly
      higher in GG than in DNT. Expression of APP, DR6, pTau (in GG and DNT) and
      caspase-3 (in GG) positively correlated with duration of epilepsy. In GG, the
      expression of neuronal caspase-3, DR6 and glial p62 was associated with a worse
      postoperative seizure outcome. CONCLUSIONS: Our observations in GNT provide
      evidence of premature activation of mechanisms of neurodegeneration which are
      associated with the clinical course of epilepsy in patient with GG.

PMID- 24750068
TI  - The evaluation of human tenon's fibroblasts and endothelial cell responses to
      antifibrotics alone and in combination with alpha-tocopherol.
AB  - PURPOSE: We aimed to evaluate the influence of current antifibrotic agents as
      well as the possible results obtained by combining these agents. This study
      included alpha-tocopherol, a strong antifibrotic and an efficient neuromediator
      of pathways used by other agents. MATERIALS AND METHODS: Mitochondrial Bcl-2,
      Bax, cytochrome c and cytoplasmic caspase-3 expression, as well as toxic effect
      patterns, mitosis and cellular reactions due to alpha-tocopherol alone or
      combined with paclitaxel, mitomycin C and 5-flurouracil (5-FU), was studied in
      series obtained from human endothelial and primary Tenon's fibroblast cell
      cultures. RESULTS: The strongest apoptotic effect in both cell groups belonged to
      paclitaxel, followed by mitomycin C, and despite the overall suppressive effect
      of the alpha-tocopherol combination, mitomycin C increased its efficiency on the
      endothelial cells. The apoptosis/necrosis ratio was highest in alpha-tocopherol
      and lowest in paclitaxel, with alpha-tocopherol generally decreasing necrosis.
      Bax was observed at a high level with mitomycin C. Cytotoxicity was the highest
      with paclitaxel, and the caspase-3 reaction was markedly higher with mitomycin C
      in both cell types. In the alpha-tocopherol and 5-FU slides, mitosis and a
      layered formation were observed. The addition of alpha-tocopherol reduced the
      cytotoxicity of all antifibrotic agents in both cell series by decreasing the
      cell numbers, leading to necrosis. CONCLUSIONS: Alone or in combination, the use
      of alpha-tocopherol and 5-FU is safer than other agents. By suppressing the
      cytotoxic effects of other antifibrotic agents, alpha-tocopherol is a promising
      drug for improving the effects of antifibrotics in many aspects of medicine. In
      addition, it has the potential to play a role beyond its antioxidant and
      antifibrotic activity in ocular surgery.

PMID- 24750070
TI  - A new standard of sexual behavior? Are claims associated with the "hookup
      culture" supported by general social survey data?
AB  - Popular media have described intimate relationships among contemporary college
      students as dominated by a pervasive sexual "hookup culture," implying that
      students are involved in frequent sexual encounters pursued by both participants
      without the expectation of a continuing relationship. The hookup culture has been
      described as "a nationwide phenomenon that has largely replaced traditional
      dating on college campuses" (Bogle, 2008 , p. 5). We tested whether these claims
      are supported among young adults (18-25) who had completed at least one year of
      college. Contrasting 1988-1996 waves of the General Social Survey with 2004-2012
      waves, we found respondents from the current era did not report more sexual
      partners since age 18, more frequent sex, or more partners during the past year
      than respondents from the earlier era. Sexually active respondents from the
      current era were more likely than those from the earlier era to report sex with a
      casual date/pickup or friend, and less likely to report sex with a spouse/regular
      partner. These modest changes are consistent with cultural shifts in the
      "scripts" and terminology surrounding sexuality. We find no evidence of
      substantial changes in sexual behavior that would indicate a new or pervasive
      pattern of non-relational sex among contemporary college students. 

PMID- 24750069
TI  - Mesenchymal stem cells regulate airway contractile tissue remodeling in murine
      experimental asthma.
AB  - BACKGROUND: Mesenchymal stem cells may offer therapeutic potential for asthma due
      to their immunomodulatory properties and host tolerability, yet prior evidence
      suggests that bloodborne progenitor cells may participate in airway remodeling.
      Here, we tested whether mesenchymal stem cells administered as anti-inflammatory
      therapy may favor airway remodeling and therefore be detrimental. METHODS:
      Adipose tissue-derived mesenchymal stem cells were retrovirally transduced to
      express green fluorescent protein and intravenously injected into mice with
      established experimental asthma induced by repeat intranasal house dust mite
      extract. Controls were house dust mite-instilled animals receiving intravenous
      vehicle or phosphate-buffered saline-instilled animals receiving mesenchymal stem
      cells. Data on lung function, airway inflammation, and remodeling were collected
      at 72 h after injection or after 2 weeks of additional intranasal challenge.
      RESULTS: The mesenchymal stem cells homed to the lungs and rapidly downregulated
      airway inflammation in association with raised T-helper-1 lung cytokines, but
      such effect declined under sustained allergen challenge despite a persistent
      presence of mesenchymal stem cells. Conversely, airway hyperresponsiveness and
      contractile tissue underwent a late reduction regardless of continuous pathogenic
      stimuli and inflammatory rebound. Tracking of green fluorescent protein did not
      show mesenchymal stem cell integration or differentiation in airway wall tissues.
      CONCLUSIONS: Therapeutic mesenchymal stem cell infusion in murine experimental
      asthma is free of unwanted pro-remodeling effects and ameliorates airway hyper
      responsiveness and contractile tissue remodeling. These outcomes support
      furthering the development of mesenchymal stem cell-based asthma therapies,
      although caution and solid preclinical data building are warranted.

PMID- 24750071
TI  - Magnetic sponge phenomena associated with interchain dipole-dipole interactions
      in a series of ferrimagnetic chain compounds doped with minor diamagnetic
      species.
AB  - The donor/acceptor ionic chain (i.e., the D(+)A(-) chain) [Ru2(2-MeO-4
      ClPhCO2)4(BTDA-TCNQ)].2.5(benzene) (1; 2-MeO-4-ClPhCO2(-) = 2-methoxy-4
      chlorobenzoate; BTDA-TCNQ = bis(1,2,5-thiadiazolo)tetracyanoquinodimethane) is a
      ferrimagnetic chain with S = 3/2 from [Ru2(II,III)](+) (i.e., D(+)) and S = 1/2
      from BTDA-TCNQ(*-) (i.e., A(-)), with J ~ -100 K, in which long-range
      antiferromagnetic ordering at TN = 11 K occurs because interchain
      antiferromagnetic interactions are critical. Compound 1 undergoes a reversible
      crystal-to-crystal structural transformation with the elimination/absorption of
      the crystallization solvent to form the dried compound [Ru2(2-MeO-4
      ClPhCO2)4(BTDA-TCNQ)] (1'), which has a higher TN (14 K). This change is clearly
      caused by the shortening of the interchain distances because the exchange
      coupling parameter for the chain is the same in both 1 and 1'. The chain
      compounds in 1 can be doped with minor diamagnetic [Rh2(II,II)] species,
      [{(Ru2)(1-x)(Rh2)(x)(2-MeO-4-ClPhCO2)4}(BTDA-TCNQ)].2.5(benzene) (x = 0.03 for Rh
      3%; x = 0.05 for Rh-5%; x = 0.16 for Rh-16%), which shifts the TN to lower
      temperatures, the magnitude of the shift being dependent on the doping ratio x
      (TN = 5.9 K for Rh-3%, TN = 3.7 K for Rh-5%, and TN was not observed above 1.8 K
      for Rh-16%). Drying a doped compound increased its TN, as was found for 1': TN =
      9.9 K for Rh-3%', TN = 9.2 K for Rh-5%', and TN was not observed above 1.8 K for
      Rh-16%'. TN had a linear relationship with the doping ratio x of the [Rh2]
      species in both the fresh and dried compounds. The TN linear relationship is
      associated with the magnitude of the effective magnetic dipole (i.e., the average
      correlation length) in the chains caused by the [Rh2] defects as well as
      naturally generated defects in the synthetic process and with the interchain
      distances affected by the crystal-to-crystal transformations. These results
      demonstrate that slightly modifying the short-range correlation lengths, which
      changes the magnetic dipole magnitudes, strongly affects the bulk
      antiferromagnetic transition, with key dipole-dipole interactions, in low
      dimensional anisotropic systems.

PMID- 24750072
TI  - Efficacy of polyMPC-DOX prodrugs in 4T1 tumor-bearing mice.
AB  - We report the in vivo efficacy, in tumor-bearing mice, of cancer prodrugs
      consisting of poly(methacryloyloxyethyl phosphorylcholine) (polyMPC) conjugated
      to doxorubicin (DOX). Our synthesis of polyMPC-DOX conjugates established
      prodrugs with tunable drug loading, pH sensitive release kinetics, and a maximum
      tolerated dose in the range of 30-50 mg/kg (DOX equivalent) in healthy mice. Here
      we show prolonged circulation of polyMPC-DOX, with a measured in vivo half-life
      (t1/2) 8 times greater than that of the free drug. We observed reduced drug
      uptake in healthy tissue, and 2-3 times enhanced drug accumulation in tumors for
      polyMPC-DOX prodrugs compared to free DOX, using BALB/c mice bearing 4T1 tumors.
      Prolonged survival and reduced tumor growth were observed in mice receiving the
      polyMPC-DOX prodrug treatment. Moreover, we evaluated immunogenicity of polyMPC
      DOX prodrugs by examining complete blood count (CBC) and characteristic cytokine
      responses, demonstrating no apparent innate or adaptive immune system response. 

PMID- 24750074
TI  - An exploration of family therapists' beliefs about the ethics of conversion
      therapy: the influence of negative beliefs and clinical competence with lesbian,
      gay, and bisexual clients.
AB  - The majority of the literature on conversion therapy has focused on clients'
      experiences and rationales for seeking such therapy. This study sought to explore
      differences in the beliefs and clinical competence of therapists who practice and
      believe in the ethics of conversion therapy and those who do not. The sample for
      this study included 762 family therapists who were members of the American
      Association of Marriage and Family Therapy. Data were collected using electronic
      surveys that assessed participants' negative beliefs about and perceived clinical
      competence with lesbian, gay, and bisexual (LGB) individuals. Results indicate
      that those who believe in the ethics of and/or practice conversion therapy report
      statistically higher levels of negative beliefs about LGB individuals and lower
      levels of clinical competence working with LGB clients. Implications for clinical
      practice and organizational policy are discussed. 

PMID- 24750075
TI  - Mind the gap: why many geneticists and psychological scientists have discrepant
      views about gene-environment interaction (G*E) research.
AB  - As our field seeks to elucidate the biopsychosocial etiologies of mental health
      disorders, many traditional psychological and social science researchers have
      added, or plan to add, genetic components to their programs of research. An
      understanding of the history, methods, and perspectives of the psychiatric
      genetics community is useful in this pursuit. In this article we provide a brief
      overview of psychiatric genetic methods and findings. This overview lays the
      groundwork for a more thorough review of gene-environment interaction (G*E)
      research and the candidate gene approach to G*E research that remains popular
      among many psychologists and social scientists. We describe the differences in
      perspective between psychiatric geneticists and psychological scientists that
      have contributed to a growing divide between the research cited and conducted by
      these two related disciplines. Finally, we outline a strategy for the future of
      research on gene-environment interactions that capitalizes on the relative
      strengths of each discipline. (PsycINFO Database Record (c) 2014 APA, all rights
      reserved). 

PMID- 24750073
TI  - The alpha3beta4* nicotinic ACh receptor subtype mediates physical dependence to
      morphine: mouse and human studies.
AB  - BACKGROUND AND PURPOSE: Recent data have indicated that alpha3beta4* neuronal
      nicotinic (n) ACh receptors may play a role in morphine dependence. Here we
      investigated if nACh receptors modulate morphine physical withdrawal.
      EXPERIMENTAL APPROACHES: To assess the role of alpha3beta4* nACh receptors in
      morphine withdrawal, we used a genetic correlation approach using publically
      available datasets within the GeneNetwork web resource, genetic knockout and
      pharmacological tools. Male and female European-American (n = 2772) and African
      American (n = 1309) subjects from the Study of Addiction: Genetics and
      Environment dataset were assessed for possible associations of polymorphisms in
      the 15q25 gene cluster and opioid dependence. KEY RESULTS: BXD recombinant mouse
      lines demonstrated an increased expression of alpha3, beta4 and alpha5 nACh
      receptor mRNA in the forebrain and midbrain, which significantly correlated with
      increased defecation in mice undergoing morphine withdrawal. Mice overexpressing
      the gene cluster CHRNA5/A3/B4 exhibited increased somatic signs of withdrawal.
      Furthermore, alpha5 and beta4 nACh receptor knockout mice expressed decreased
      somatic withdrawal signs compared with their wild-type counterparts. Moreover,
      selective alpha3beta4* nACh receptor antagonists, alpha-conotoxin AuIB and AT
      1001, attenuated somatic signs of morphine withdrawal in a dose-related manner.
      In addition, two human datasets revealed a protective role for variants in the
      CHRNA3 gene, which codes for the alpha3 nACh receptor subunit, in opioid
      dependence and withdrawal. In contrast, we found that the alpha4beta2* nACh
      receptor subtype is not involved in morphine somatic withdrawal signs. CONCLUSION
      AND IMPLICATIONS: Overall, our findings suggest an important role for the
      alpha3beta4* nACh receptor subtype in morphine physical dependence.

PMID- 24750076
TI  - Psychology and social networks: a dynamic network theory perspective.
AB  - Research on social networks has grown exponentially in recent years. However,
      despite its relevance, the field of psychology has been relatively slow to
      explain the underlying goal pursuit and resistance processes influencing social
      networks in the first place. In this vein, this article aims to demonstrate how a
      dynamic network theory perspective explains the way in which social networks
      influence these processes and related outcomes, such as goal achievement,
      performance, learning, and emotional contagion at the interpersonal level of
      analysis. The theory integrates goal pursuit, motivation, and conflict
      conceptualizations from psychology with social network concepts from sociology
      and organizational science to provide a taxonomy of social network role
      behaviors, such as goal striving, system supporting, goal preventing, system
      negating, and observing. This theoretical perspective provides psychologists with
      new tools to map social networks (e.g., dynamic network charts), which can help
      inform the development of change interventions. Implications for social,
      industrial-organizational, and counseling psychology as well as conflict
      resolution are discussed, and new opportunities for research are highlighted,
      such as those related to dynamic network intelligence (also known as cognitive
      accuracy), levels of analysis, methodological/ethical issues, and the need to
      theoretically broaden the study of social networking and social media behavior.
      (PsycINFO Database Record (c) 2014 APA, all rights reserved). 

PMID- 24750077
TI  - Charles Donald Spielberger (1927-2013).

PMID- 24750078
TI  - Hedda Bolgar (1909-2013).

PMID- 24750079
TI  - Marvin Reznikoff (1925-2013).

PMID- 24750080
TI  - Ian Porteous Howard (1927-2013).

PMID- 24750081
TI  - Irving Aaron Jacobs (1929-2013).

PMID- 24750082
TI  - Jule Dewayne Moravec (1933-2013).

PMID- 24750085
TI  - Violent media games and aggression-Is it really time for a mea culpa?

PMID- 24750086
TI  - Supreme Court decision on violent video games was based on the First Amendment,
      not scientific evidence.

PMID- 24750087
TI  - A way forward for video game violence research.

PMID- 24750088
TI  - Racism inflation.

PMID- 24750089
TI  - The real meaning of color-blind racial ideology.

PMID- 24750090
TI  - The reality of racism based on the illusion of "race".

PMID- 24750091
TI  - "Perceived" discrimination as an example of color-blind racial ideology's
      influence on psychology.

PMID- 24750092
TI  - Why racial color-blindness is myopic.

PMID- 24750093
TI  - Genome-wide association implicates numerous genes underlying ecological trait
      variation in natural populations of Populus trichocarpa.
AB  - In order to uncover the genetic basis of phenotypic trait variation, we used 448
      unrelated wild accessions of black cottonwood (Populus trichocarpa) from much of
      its range in western North America. Extensive data from large-scale trait
      phenotyping (with spatial and temporal replications within a common garden) and
      genotyping (with a 34 K Populus single nucleotide polymorphism (SNP) array) of
      all accessions were used for gene discovery in a genome-wide association study
      (GWAS). We performed GWAS with 40 biomass, ecophysiology and phenology traits and
      29,355 filtered SNPs representing 3518 genes. The association analyses were
      carried out using a Unified Mixed Model accounting for population structure
      effects among accessions. We uncovered 410 significant SNPs using a Bonferroni
      corrected threshold (P<1.7*10(-6)). Markers were found across 19 chromosomes,
      explained 1-13% of trait variation, and implicated 275 unique genes in trait
      associations. Phenology had the largest number of associated genes (240 genes),
      followed by biomass (53 genes) and ecophysiology traits (25 genes). The GWAS
      results propose numerous loci for further investigation. Many traits had
      significant associations with multiple genes, underscoring their genetic
      complexity. Genes were also identified with multiple trait associations within
      and/or across trait categories. In some cases, traits were genetically correlated
      while in others they were not.

PMID- 24750094
TI  - Pediatric headache: where have we been and where do we need to be.
AB  - In this article, we hope to summarize current understanding of pediatric
      headache. We discuss epidemiology, genetics, classification, diagnosis,
      outpatient, emergency and inpatient treatment options, prevention strategies, and
      behavioral approaches. For each section, we end with a series of questions for
      future research and consideration. 

PMID- 24750095
TI  - Breast cancer diagnosis and factors influencing treatment decisions in Ghana.
AB  - Researchers in this study explored the reactions of women with breast cancer and
      identified factors influencing treatment decisions. A qualitative exploratory
      approach was employed. Participants were recruited from a tertiary hospital and a
      breast cancer support group. Purposive sampling recruited 12 women. It was found
      that women identified breast lesions accidentally or intentionally and that
      diagnosis was delayed. Emotional reactions to diagnosis included shock and
      sadness. Factors that influenced treatment were the influence of other people,
      alternative sources of treatment, faith and support, knowledge, "tuning the
      mind," and effects on intimacy. Health professionals should develop effective
      communication and counseling skills for clients. 

PMID- 24750097
TI  - Bayesian estimation of the phylogeography of African gorillas with genome
      differentiated population trees.
AB  - Phylogeography investigates the historical process that is responsible for the
      contemporary geographic distributions of populations in a species. The inference
      is made on the basis of molecular sequence data sampled from modern-day
      populations. The estimates, however, may fluctuate depending on the relevant
      genomic regions, because the evolution mechanism of each genome is unique, even
      within the same individual. In this article, we propose a genome-differentiated
      population tree model that allows the existence of separate population trees for
      each homologous genome. In each population tree, the unique evolutionary
      characteristics account for each genome, along with their homologous
      relationship; therefore, the approach can distinguish the evolutionary history of
      one genome from that of another. In addition to the separate divergence times,
      the new model can estimate separate effective population sizes, gene-genealogies
      and other mutation parameters. For Bayesian inference, we developed a Markov
      chain Monte Carlo (MCMC) methodology with a novel MCMC algorithm which can mix
      over a complicated state space. The stability of the new estimator is
      demonstrated through comparison with the Monte Carlo samples and other methods,
      as well as MCMC convergence diagnostics. The analysis of African gorilla data
      from two homologous loci reveals discordant divergence times between loci, and
      this discrepancy is explained by male-mediated gene flows until the end of the
      last ice age.

PMID- 24750098
TI  - Heterobimetallic porphyrin complexes displaying triple dynamics: coupled metal
      motions controlled by constitutional evolution.
AB  - A bis-strap porphyrin ligand (1), with an overhanging carboxylic acid group on
      each side of the macrocycle, has been investigated toward the formation of
      dynamic libraries of bimetallic complexes with Hg(II), Cd(II), and Pb(II). Highly
      heteroselective metalation processes occurred in the presence of Pb(II), with
      Hg(II) or Cd(II) bound out-of-plane to the N-core and "PbOAc" bound to a
      carboxylate group of a strap on the opposite side. The resulting complexes,
      1(Hg).PbOAc and 1(Cd).PbOAc, display three levels of dynamics. The first is strap
      level (interactional dynamics), where the PbOAc moiety swings between the left
      and right side of the strap owing to a second sphere of coordination with lateral
      amide functions. The second is ligand-level (motional dynamics), where
      1(Hg).PbOAc and 1(Cd).PbOAc exist as two degenerate states in equilibrium
      controlled by a chemical effector (AcO(-)). The process corresponds to a double
      translocation of the metal ions according to an intramolecular migration of
      Hg(II) or Cd(II) through the N-core, oscillating between the two equivalent
      overhanging carbonyl groups, coupled to an intermolecular pathway for PbOAc
      exchanging between the two equivalent overhanging carboxylate groups (N-core(up)
      ? N-core(down) coupled to strap(down) ? strap(up), i.e., coupled motion #1 in the
      abstract graphic). The third is library-level (constitutional dynamics), where a
      dynamic constitutional evolution of the system was achieved by the successive
      addition of two chemical effectors (DMAP and then AcO(-)). It allowed shifting
      equilibrium forward and backward between 1(Hg).PbOAc and the corresponding
      homobimetallic complexes 1(Hg2).DMAP and 1(Pb).PbOAc. The latter displays a
      different ligand-level dynamics, in the form of an intraligand coupled migration
      of the Pb(II) ions (N-core(up) ? strap(up) coupled to strap(down) ? N-core(down),
      i.e., coupled motion #2 in the abstract graphic). In addition, the neutral
      "bridged" complexes 1HgPb and 1CdPb, with the metal ions on opposite sides both
      bound to the N-core and to a carboxylate of a strap, were structurally
      characterized. These results establish an unprecedented approach in
      supramolecular coordination chemistry, by considering the reversible interaction
      of a metal ion with the porphyrin N-core as a new source of self-organization
      processes. This work should provide new inspirations for the design of innovative
      adaptative materials and devices.

PMID- 24750096
TI  - Global incidence of human Shiga toxin-producing Escherichia coli infections and
      deaths: a systematic review and knowledge synthesis.
AB  - OBJECTIVES: Shiga toxin-producing Escherichia coli (STEC) are an important cause
      of foodborne disease, yet global estimates of disease burden do not exist. Our
      objective was to estimate the global annual number of illnesses due to pathogenic
      STEC, and resultant hemolytic uremic syndrome (HUS), end-stage renal disease
      (ESRD), and death. MATERIALS: We searched Medline, Scopus, SIGLE/OpenGrey, and
      CABI and World Health Organization (WHO) databases for studies of STEC incidence
      in the general population, published between January 1, 1990 and April 30, 2012,
      in all languages. We searched health institution websites for notifiable disease
      data and reports, cross-referenced citations, and consulted international
      knowledge experts. We employed an a priori hierarchical study selection process
      and synthesized results using a stochastic simulation model to account for
      uncertainty inherent in the data. RESULTS: We identified 16 articles and
      databases from 21 countries, from 10 of the 14 WHO Sub-Regions. We estimated that
      STEC causes 2,801,000 acute illnesses annually (95% Credible Interval [Cr.I.]:
      1,710,000; 5,227,000), and leads to 3890 cases of HUS (95% Cr.I.: 2400; 6700),
      270 cases of ESRD (95% Cr.I.: 20; 800), and 230 deaths (95% Cr.I.: 130; 420).
      Sensitivity analyses indicated these estimates are likely conservative.
      CONCLUSIONS: These are the first estimates of the global incidence of STEC
      related illnesses, which have not been explicitly included in previous global
      burden of disease estimations. Compared to other pathogens with a foodborne
      transmission component, STEC appears to cause more cases than alveolar
      echinococcosis each year, but less than typhoid fever, foodborne trematodes, and
      nontyphoidal salmonellosis. APPLICATIONS: Given the persistence of STEC globally,
      efforts aimed at reducing the burden of foodborne disease should consider the
      relative contribution of STEC in the target population.

PMID- 24750099
TI  - An efficient and rapid thin-layer chromatography method for the identification of
      32 dye substances in hair dye products.
AB  - OBJECTIVE: The use of dye substances in hair dye products has led to
      controversial public and scientific discussions about their impact on human
      health. This study aimed to explore a rapid method for identification of dye
      substances in hair dye products. METHODS: Thin layer chromatography (TLC) method
      was conducted in this study. We developed basic data of 32 dye substances by 4
      developing solvents and 2 indicator sprays. The dye substances were identified by
      comparing the Rf values and colors between samples and reference substances.
      RESULTS: Thirty samples were identified by the established method. 22 hair dye
      substances were detected in 16 formula known samples, 15 hair dye substances were
      detected in 14 formula unknown samples. Four laboratories participated in the
      validation and the results showed good interlaboratory reproducibility.
      CONCLUSION: The developed TLC method is simple, rapid, reliable and can be finely
      used for identification of dye substances in hair dye products.

PMID- 24750100
TI  - Intervention trials for prevention of metabolic syndrome and type 2 diabetes:
      focus on Asian Indians.
AB  - Prevalence of diabetes continues to increase in urban areas, and escalation is
      discernible in semi-urban and rural areas. It is reported to affect Asian Indians
      a decade earlier compared with other populations, and complications (e.g.,
      nephropathy) occur earlier and are severe and more prevalent than in other races.
      Because of these adverse features and suboptimal management practices, type 2
      diabetes mellitus (T2DM) poses a huge health and economic burden to the country.
      Simple and culturally sensitive interventions for Asian Indians have been shown
      to be effective in prevention/amelioration of diabetes and other cardiovascular
      risk factors in multiple settings, among urban and rural residents, in migrants,
      and in those who are healthy or obese or have metabolic syndrome or T2DM.
      Furthermore, short-term intensive lifestyle intervention in children improves
      anthropometric and metabolic parameters. Finally, intervention with specific
      nutrient or oil substitution in Indian diets has been reported to produce benefit
      in multiple metabolic cardiovascular risk factors. There is, however, further
      need for conducting well-designed and planned intervention trials with robust
      outcome data at the primary and secondary levels. These trials must be culturally
      sensitive and should investigate cost-effective strategies.

PMID- 24750101
TI  - PAR1 antagonists inhibit thrombin-induced platelet activation whilst leaving the
      PAR4-mediated response intact.
AB  - Thrombin-induced platelet activation is initiated by PAR1 and PAR4 receptors.
      Vorapaxar, a PAR1 antagonist, has been assessed in patients with acute coronary
      syndromes (ACS) and stable atherosclerotic disease in addition to standard-of
      care treatment. In clinical trials, vorapaxar has been observed to reduce the
      frequency of ischaemic events in some subgroups though in others has increased
      the frequency of bleeding events. Among patients undergoing CABG surgery, which
      is associated with excess thrombin generation, bleeding was not increased. The
      aim of these studies was to investigate the effects of selective PAR1 antagonism
      on thrombin-induced platelet activation in patients receiving vorapaxar or
      placebo in the TRACER trial and to explore the roles of PAR1 and PAR4 in thrombin
      induced platelet activation in healthy volunteers. ACS patients receiving
      vorapaxar or placebo in the TRACER trial were studied at baseline and 4 hours, 1
      and 4 months during drug administration. Thrombin-induced calcium mobilisation in
      platelet-rich plasma was assessed by flow cytometry. In vitro studies were
      performed in healthy volunteers using the PAR1 antagonist SCH79797 or PAR4
      receptor desensitisation. Vorapaxar treatment significantly inhibited thrombin
      induced calcium mobilisation, leaving a residual, delayed response. These
      findings were consistent with calcium mobilisation mediated via the PAR4 receptor
      and were reproduced in vitro using SCH79797. PAR4 receptor desensitization, in
      combination with SCH79797, completely inhibited thrombin-induced calcium
      mobilisation confirming that the residual calcium mobilisation was mediated via
      PAR4. In conclusion vorapaxar selectively antagonises the PAR1-mediated component
      of thrombin-induced platelet activation, leaving the PAR4-mediated response
      intact, which may explain why vorapaxar is well tolerated in patients undergoing
      CABG surgery since higher thrombin levels in this setting may override the
      effects of PAR1 antagonism through PAR4 activation, thus preserving haemostasis.
      Further assessment may be warranted.

PMID- 24750102
TI  - Evaluation of effect of impaired renal function on lamivudine pharmacokinetics.
AB  - AIMS: This study aimed to describe lamivudine pharmacokinetics in patients with
      impaired renal function and to evaluate the consistency of current dosing
      recommendations. METHODS: A total of 244 patients, ranging in age from 18 to 79
      years (median 40 years) and in bodyweight from 38 to 117 kg (median 71 kg), with
      344 lamivudine plasma concentrations, were analysed using a population
      pharmacokinetic analysis. Serum creatinine clearance (CLCR) was calculated using
      the Cockcroft-Gault formula; 177 patients had normal renal function (CLCR > 90 ml
      min(-1) ), 50 patients had mild renal impairment (CLCR = 60-90 ml min(-1) ), 20
      patients had moderate renal impairment (CLCR = 30-60 ml min(-1) ), and five
      patients had severe renal impairment (CLCR < 30 ml min(-1) ). RESULTS: A two
      compartment model adequately described the data. Typical population estimates
      (percentage interindividual variability) of the apparent clearance (CL/F),
      central (Vc /F) and peripheral volumes of distribution (Vp /F),
      intercompartmental clearance (Q/F) and absorption rate constant (Ka ) were 29.7 l
      h(-1) (32%), 68.2 l, 114 l, 10.1 l h(-1) (85%) and 1 h(-1) , respectively.
      Clearance increased significantly and gradually with CLCR. Our simulations showed
      that a dose of 300 mg day(-1) in patients with mild renal impairment could
      overexpose them. A dose of 200 mg day(-1) maintained an exposure close to that of
      adults with normal renal function. However, the current US Food and Drug
      Administration recommendations for lamivudine in other categories of patients
      (from severe to moderate renal impairment) provided optimal exposures.
      CONCLUSIONS: Lamivudine elimination clearance is related to renal function. To
      provide optimal exposure, patients with mild renal impairment should receive 200
      mg day(-1) instead of 300 mg day(-1) .

PMID- 24750103
TI  - Persistence of recipient human leucocyte antigen (HLA) antibodies and production
      of donor HLA antibodies following reduced intensity allogeneic haematopoietic
      stem cell transplantation.
AB  - The effects of reduced intensity conditioning (RIC) on human leucocyte antigen
      (HLA)-alloimmunization and platelet transfusion refractoriness (PTR) following
      allogeneic haematopoietic stem cell transplantation (Allo-HSCT) are unknown. We
      studied HLA-alloantibodies in a cohort of 16 patients (eight HLA-alloimmunized
      with pre-transplant histories of PTR and eight non-alloimmunized controls)
      undergoing Allo-HSCT using fludarabine/cyclophosphamide-based RIC. Pre- and post
      transplant serum samples were analysed for HLA-antibodies and compared to
      myeloid, T-cell and bone marrow plasma cell chimaerism. Among alloimmunized
      patients, the duration that HLA-antibodies persisted post-transplant correlated
      strongly with pre-transplant HLA-antibody mean fluorescence intensity (MFI) and
      PRA levels (Spearman's rank correlation = 0.954 (P = 0.0048) and 0.865 (P =
      0.0083) respectively). Pre-transplant MFI >10,000 was associated with post
      transplant HLA antibody persistence >100 d (P = 0.029). HLA-antibodies persisted
      >=100 d in 3/8 patients despite recipient chimaerism being undetectable in all
      lympho-haematopoietic lineages including plasma cells. Post-transplant de-novo
      HLA-antibodies developed in three control patients with two developing PTR; the
      donors for two of these patients demonstrated pre-existing HLA-antibodies of
      equivalent specificity to those in the patient, confirming donor origin. These
      data show HLA-antibodies may persist for prolonged periods following RIC. Further
      study is needed to determine the incidence of post-transplant PTR as a
      consequence of donor-derived HLA alloimmunization before recommendations on donor
      HLA-antibody screening can be made.

PMID- 24750104
TI  - Lithium binaphtholate-catalyzed asymmetric addition of lithium acetylides to
      carbonyl compounds.
AB  - The asymmetric addition of lithium acetylides to carbonyl compounds in the
      presence of a chiral lithium binaphtholate catalyst was developed. A procedure
      involving the slow addition of carbonyl compounds to lithium acetylides improved
      the enantioselectivity. This reaction afforded diverse chiral secondary and
      tertiary propargylic alcohols in high yields and with good to high
      enantioselectivities. 

PMID- 24750105
TI  - Sex and gender diversity among transgender persons in Ontario, Canada: results
      from a respondent-driven sampling survey.
AB  - Recent estimates suggest that as many as 1 in 200 adults may be trans
      (transgender, transsexual, or transitioned). Knowledge about dimensions of sex
      and gender in trans populations is crucial to development of inclusive policy,
      practice, and research, but limited data have been available, particularly from
      probability samples. The Trans PULSE community-based research project surveyed
      trans Ontarians (n=433) in 2009-2010 using respondent-driven sampling.
      Frequencies were weighted by recruitment probability to produce estimates for the
      networked Ontario trans population. An estimated 30% of trans Ontarians were
      living their day-to-day lives in their birth gender, and 23% were living in their
      felt gender with no medical intervention. In all, 42% were using hormones, while
      15% of male-to-female spectrum persons had undergone vaginoplasty and 0.4% of
      female-to-male spectrum persons had had phalloplasty. Of those living in their
      felt gender, 59% had begun to do so within the past four years. A minority of
      trans Ontarians reported a linear transition from one sex to another, yet such a
      trajectory is often assumed to be the norm. Accounting for this observed
      diversity, we recommend policy and practice changes to increase social inclusion
      and service access for trans persons, regardless of transition status.

PMID- 24750106
TI  - Feasibility and acceptability of a bar-based sexual risk reduction intervention
      for bar patrons in Tshwane, South Africa.
AB  - Alcohol consumption is a recognised risk factor for HIV infection. Alcohol
      serving establishments have been identified as appropriate venues in which to
      deliver HIV prevention interventions. This paper describes experiences and
      lessons learnt from implementing a combined HIV prevention intervention in bar
      settings in one city- and one township-based bar in Tshwane, South Africa. The
      intervention consisted of peer-led and brief intervention counselling sub
      components. Thirty-nine bar patrons were recruited and trained, and delivered HIV
      and alcohol risk reduction activities to their peers as peer interventionists. At
      the same time, nine counsellors received training and visited the bars weekly to
      provide brief motivational interviewing counselling, advice, and referrals to the
      patrons of the bars. A responsible server sub-component that had also been
      planned was not delivered as it was not feasible to train the staff in the two
      participating bars. Over the eight-month period the counsellors were approached
      by and provided advice and counselling for alcohol and sexual risk-related
      problems to 111 bar patrons. The peer interventionists reported 1323 risk
      reduction interactions with their fellow bar patrons during the same period. The
      intervention was overall well received and suggests that bar patrons and servers
      can accept a myriad of intervention activities to reduce sexual risk behaviour
      within their drinking settings. However, HIV- and AIDS-related stigma hindered
      participation in certain intervention activities in some instances. The buy-in
      that we received from the relevant stakeholders (i.e. bar owners/managers and
      patrons, and the community at large) was an important contributor to the
      feasibility and acceptability of the intervention.

PMID- 24750107
TI  - Effect of additional preoperative administration of the neutrophil elastase
      inhibitor sivelestat on perioperative inflammatory response after pediatric heart
      surgery with cardiopulmonary bypass.
AB  - Cardiopulmonary bypass (CPB) elicits a systemic inflammatory response. Our
      previous reports revealed that prophylactic sivelestat administration at CPB
      initiation suppresses the postoperative acute inflammatory response due to CPB in
      pediatric cardiac surgery. The purpose of this study was to compare the effects
      of sivelestat administration before CPB and at CPB initiation in patients
      undergoing pediatric open-heart surgery. Twenty consecutive patients weighing 5
      10 kg and undergoing ventricular septal defect closure with CPB were divided into
      pre-CPB (n = 10) and control (n = 10) groups. Patients in the pre-CPB group
      received a 24 h continuous intravenous infusion of 0.2 mg/kg/h sivelestat
      starting at the induction of anesthesia and an additional 0.1 mg/100 mL during
      CPB priming. Patients in the control group received a 24-h continuous intravenous
      infusion of 0.2 mg/kg/h sivelestat starting at the commencement of CPB. Blood
      samples were tested. Clinical variables including blood loss, water balance,
      systemic vascular resistance index, and the ratio between partial pressure of
      oxygen and fraction of inspired oxygen (P/F ratio) were assessed. White blood
      cell count and neutrophil count as well as C-reactive protein levels were
      significantly lower in the pre-CPB group according to repeated two-way analysis
      of variance, whereas platelet count was significantly higher. During CPB, mixed
      venous oxygen saturation remained significantly higher and lactate levels lower
      in the pre-CPB group. Postoperative alanine aminotransferase and blood urea
      nitrogen levels were significantly lower in the pre-CPB group than in the control
      group. The P/F ratio was significantly higher in the pre-CPB group than in the
      control group. Fluid load requirement was significantly lower in the pre-CPB
      group.Administration of sivelestat before CPB initiation is more effective than
      administration at initiation for the suppression of inflammatory responses due to
      CPB in pediatric open-heart surgery, with this effect being confirmed by clinical
      evidence.

PMID- 24750108
TI  - Differentiating the location of cervical lymph node metastasis is very useful for
      estimating the risk of distant metastases in papillary thyroid carcinoma.
AB  - OBJECTIVE: A larger primary tumour size, greater numbers of cervical lymph node
      (LN) metastasis are associated with a higher risk of distant metastases in
      papillary thyroid carcinoma (PTC). However, the impact of the location of
      cervical LN metastasis on distant metastasis is controversial. The aim of this
      study was to evaluate the risk of distant metastases according to the tumour size
      and LN status in PTC patients, with special consideration of the LN metastasis
      pattern. PATIENTS: This retrospective cohort study reviewed 1700 classical PTC
      patients who underwent initial thyroid surgery at Asan Medical Center between
      2000 and 2004. RESULTS: The cumulative risk of distant metastases was increased
      with the increase in tumour size and was significantly different according to the
      location of involved LNs by the tumour node metastasis (TNM) staging. The
      cumulative risk in pN1b group showed the steepest increasing pattern with the
      increase in tumour size compared with pN1a and pN0/Nx group. When we analysed the
      cumulative risk of distant metastases according to the number of involved LNs,
      patients with more than 20 involved LNs also had the steepest increase in the
      risk of distant metastases with the increase in tumour size. However, only the
      location of involved LNs, not the number of involved LNs, was associated with
      distant metastases in multivariate analysis. CONCLUSIONS: We confirm that the
      location of involved LNs categories based on the TNM staging system is more
      useful than the number of involved LNs categories for estimating the risk of
      distant metastasis in PTC. Differentiating N1a disease from N1b disease is
      important for the follow-up and management of patients with PTC.

PMID- 24750109
TI  - Reliability of a novel, semi-quantitative scale for classification of structural
      brain magnetic resonance imaging in children with cerebral palsy.
AB  - AIM: To describe the development of a novel rating scale for classification of
      brain structural magnetic resonance imaging (MRI) in children with cerebral palsy
      (CP) and to assess its interrater and intrarater reliability. METHOD: The scale
      consists of three sections. Section 1 contains descriptive information about the
      patient and MRI. Section 2 contains the graphical template of brain hemispheres
      onto which the lesion is transposed. Section 3 contains the scoring system for
      the quantitative analysis of the lesion characteristics, grouped into different
      global scores and subscores that assess separately side, regions, and depth. A
      larger interrater and intrarater reliability study was performed in 34 children
      with CP (22 males, 12 females; mean age at scan of 9 y 5 mo [SD 3 y 3 mo], range
      4 y-16 y 11 mo; Gross Motor Function Classification System level I, [n=22], II
      [n=10], and level III [n=2]). RESULTS: Very high interrater and intrarater
      reliability of the total score was found with indices above 0.87. Reliability
      coefficients of the lobar and hemispheric subscores ranged between 0.53 and 0.95.
      Global scores for hemispheres, basal ganglia, brain stem, and corpus callosum
      showed reliability coefficients above 0.65. INTERPRETATION: This study presents
      the first visual, semi-quantitative scale for classification of brain structural
      MRI in children with CP. The high degree of reliability of the scale supports its
      potential application for investigating the relationship between brain structure
      and function and examining treatment response according to brain lesion severity
      in children with CP.

PMID- 24750111
TI  - Transforming growth factor-beta 1 pathways in inflammatory airway diseases.
AB  - Transforming growth factor-beta 1 (TGF-beta1) has been reported being involved in
      the remodeling and immunosuppression processes of inflammatory airway diseases;
      understanding the regulation of TGF-beta1 is therefore a key to unravel the
      pathomechanisms of these diseases. This review briefly summarizes the current
      knowledge on the influencing factors for driving TGF-beta1 and its regulatory
      pathways in inflammatory airway diseases and discusses possible therapeutic
      approaches to TGF-beta1 control. The factors include smoking and oxidative
      stress, prostaglandins (PGs), leukotrienes (LTs), bradykinin (BK), and microRNAs
      (miRs). Based on the summary, new innovative treatment strategies may be
      developed for inflammatory airway diseases with an impaired expression of TGF
      beta1.

PMID- 24750113
TI  - Cervical cancer in developing countries: effective screening and preventive
      strategies with an application in Rwanda.
AB  - In this article we explore literature regarding cervical cancer screening methods
      available in developing countries. Cervical cancer is a preventable and curable
      disease, but it continues to threaten the lives of many women. Eighty-five
      percent of cases and the majority of deaths occur in developing countries.
      Cytology via Papinicolaou (Pap) smear is not generally a suitable method of
      screening in low-resource regions. Alternative methods include visual inspection
      by acetic acid (VIA), human papillomavirus-deoxyribonucleic acid (HPV-DNA), and
      careHPV-DNA. Education is needed for health care providers and women about
      preventive immunization and screening. A Rwandan project is described to
      demonstrate effective program planning and implementation. 

PMID- 24750110
TI  - Novel therapeutic targets in myeloma bone disease.
AB  - Multiple myeloma is a neoplastic disorder of plasma cells characterized by clonal
      proliferation within the bone marrow. One of the major clinical features of
      multiple myeloma is the destructive osteolytic bone disease that occurs in the
      majority of patients. Myeloma bone disease is associated with increased
      osteoclast activity and suppression of osteoblastogenesis. Bisphosphonates have
      been the mainstay of treatment for many years; however, their use is limited by
      their inability to repair existing bone loss. Therefore, research into novel
      approaches for the treatment of myeloma bone disease is of the utmost importance.
      This review will discuss the current advances in our understanding of osteoclast
      stimulation and osteoblast suppression mechanisms in myeloma bone disease and the
      treatments that are under development to target this destructive and debilitating
      feature of myeloma. 

PMID- 24750112
TI  - Antigen 43/Fcepsilon3 chimeric protein expressed by a novel bacterial surface
      expression system as an effective asthma vaccine.
AB  - The IgE Fcepsilon3 domain is an active immunotherapeutic target for asthma and
      other allergic diseases. However, previous methods for preparing IgE fusion
      protein vaccines are complex. Antigen 43 (Ag43) is a surface protein found in
      Escherichia coli that contains alpha and beta subunits (the alpha subunit
      contains multiple T epitopes). Here we constructed a novel Ag43 surface display
      system (Ag43 system) to express Ag43 chimeric proteins to disrupt immune
      tolerance against IgE. The Ag43 system was constructed from the E. coli strain
      Tan109, in which the Ag43 gene was deleted and a recombinant plasmid (pETAg43)
      expressing a partial Ag43 gene was introduced. The Fcepsilon3 domain of the IgE
      gene was then subcloned into plasmid pETAg43, resulting in a recombinant plasmid
      pETAg43/Fcepsilon3, which was used to transform Tan109 for Ag43/Fcepsilon3
      surface expression. Thereafter, Ag43/Fcepsilon3 was investigated as an asthma
      vaccine in a mouse model. Ag43/Fcepsilon3 was expressed on and could be separated
      from the bacterial surface by heating to 60 degrees  while retaining activity.
      Ag43/Fcepsilon3, as a protein vaccine, produced neutralizing autoantibodies to
      murine IgE, induced significant anti-asthma effects, and regulated IgE and T
      helper cytokines in a murine asthma model. Data show that Ag43/Fcepsilon3
      chimeric protein is a potential model vaccine for asthma treatment, and that the
      Ag43 system may be an effective tool for novel vaccine preparation to break
      immune tolerance to other self-molecules.

PMID- 24750114
TI  - Coinage metal complexes supported by the tri- and tetraphosphine ligands.
AB  - A series of tri- and tetranuclear phosphine complexes of d(10) metal ions
      supported by the polydentate ligands, bis(diphenylphosphinomethyl)phenylphosphine
      (PPP) and tris(diphenylphosphinomethyl)phosphine (PPPP), were synthesized. All
      the compounds under study, [AuM2(PPP)2](3+) (M = Au (1), Cu (2), Ag (3)),
      [M4(PPPP)2](4+) (M = Ag (4), Au (5)), [AuAg3(PPPP)2](4+) (6), and
      [Au2Cu2(PPPP)2(NCMe)4](4+) (7), were characterized crystallographically. The
      trinuclear clusters 1-3 contain a linear metal core, while in the isostructural
      tetranuclear complexes 4-6 the metal framework has a plane star-shaped
      arrangement. Cluster 7 adopts a structural motif that involves a digold unit
      bridged by two arms of the PPPP phosphines and decorated two spatially separated
      Cu(I) ions chelated by the remaining P donors. The NMR spectroscopic
      investigation in DMSO solution revealed the heterometallic clusters 2, 3, and 6
      are stereochemically nonrigid and undergo reversible metal ions redistribution
      between several species, accompanied by their solvation-desolvation. The
      complexes 1-3 and 5-7 exhibit room temperature luminescence in the solid state
      (Phiem = 6-64%) in the spectral region from 450 to 563 nm. The phosphorescence
      observed originates from the triplet excited states, determined by the metal
      cluster-centered dsigma* -> psigma transitions. 

PMID- 24750115
TI  - Adult polyglucosan body disease with GBE1 haploinsufficiency and concomitant
      frontotemporal lobar degeneration.

PMID- 24750116
TI  - Metal-organic frameworks for air purification of toxic chemicals.

PMID- 24750117
TI  - Carbon-carbon double-bond reductases in nature.
AB  - Reduction of C = C bonds by reductases, found in a variety of microorganisms
      (e.g. yeasts, bacteria, and lower fungi), animals, and plants has applications in
      the production of metabolites that include pharmacologically active drugs and
      other chemicals. Therefore, the reductase enzymes that mediate this
      transformation have become important therapeutic targets and biotechnological
      tools. These reductases are broad-spectrum, in that, they can act on
      isolation/conjugation C = C-bond compounds, alpha,beta-unsaturated carbonyl
      compounds, carboxylic acids, acid derivatives, and nitro compounds. In addition,
      several mutations in the reductase gene have been identified, some associated
      with diseases. Several of these reductases have been cloned and/or purified, and
      studies to further characterize them and determine their structure in order to
      identify potential industrial biocatalysts are still in progress. In this study,
      crucial reductases for bioreduction of C = C bonds have been reviewed with
      emphasis on their principal substrates and effective inhibitors, their
      distribution, genetic polymorphisms, and implications in human disease and
      treatment.

PMID- 24750118
TI  - Silver nanoprism arrays coupled to functional hybrid films for localized surface
      plasmon resonance-based detection of aromatic hydrocarbons.
AB  - We report the achievement of sensitive gas detection using periodic silver
      nanoprisms fabricated by a simple and low-cost lithographic technique. The
      presence of sharp tips combined with the periodic arrangement of the nanoprisms
      allowed the excitement of isolated and interacting localized surface plasmon
      resonances. Specific sensing capabilities with respect to aromatic hydrocarbons
      were achieved when the metal nanoprism arrays were coupled in the near field with
      functional hybrid films, providing a real-time, label-free, and reversible
      methodology. Ultra-high-vacuum temperature-programmed desorption measurements
      demonstrated an interaction energy between the sensitive film and analytes in the
      range of 55-71 kJ/mol. The far-field optical properties and the detection
      sensitivity of the sensors, modeled using a finite element method, were
      correlated to experimental data from gas sensing tests. An absorbance variation
      of 1.2% could be observed and associated with a theoretical increase in the
      functional film refractive index of ~0.001, as a consequence to the interaction
      with 30 ppm xylene. The possibility of detecting such a small variation in the
      refractive index suggests the highly promising sensing capabilities of the
      presented technique. 

PMID- 24750119
TI  - Outbreaks attributed to cheese: differences between outbreaks caused by
      unpasteurized and pasteurized dairy products, United States, 1998-2011.
AB  - INTRODUCTION: The interstate commerce of unpasteurized fluid milk, also known as
      raw milk, is illegal in the United States, and intrastate sales are regulated
      independently by each state. However, U.S. Food and Drug Administration
      regulations allow the interstate sale of certain types of cheeses made from
      unpasteurized milk if specific aging requirements are met. We describe
      characteristics of these outbreaks, including differences between outbreaks
      linked to cheese made from pasteurized or unpasteurized milk. METHODS: We
      reviewed reports of outbreaks submitted to the Foodborne Disease Outbreak
      Surveillance System during 1998-2011 in which cheese was implicated as the
      vehicle. We describe characteristics of these outbreaks, including differences
      between outbreaks linked to cheese made from pasteurized versus unpasteurized
      milk. RESULTS: During 1998-2011, 90 outbreaks attributed to cheese were reported;
      38 (42%) were due to cheese made with unpasteurized milk, 44 (49%) to cheese made
      with pasteurized milk, and the pasteurization status was not reported for the
      other eight (9%). The most common cheese-pathogen pairs were unpasteurized queso
      fresco or other Mexican-style cheese and Salmonella (10 outbreaks), and
      pasteurized queso fresco or other Mexican-style cheese and Listeria (6
      outbreaks). The cheese was imported from Mexico in 38% of outbreaks caused by
      cheese made with unpasteurized milk. In at least five outbreaks, all due to
      cheese made from unpasteurized milk, the outbreak report noted that the cheese
      was produced or sold illegally. Outbreaks caused by cheese made from pasteurized
      milk occurred most commonly (64%) in restaurant, delis, or banquet settings where
      cross-contamination was the most common contributing factor. CONCLUSIONS: In
      addition to using pasteurized milk to make cheese, interventions to improve the
      safety of cheese include limiting illegal importation of cheese, strict
      sanitation and microbiologic monitoring in cheese-making facilities, and controls
      to limit food worker contamination.

PMID- 24750120
TI  - Histidine-mediated xylem loading of zinc is a species-wide character in Noccaea
      caerulescens.
AB  - Histidine plays a crucial role in nickel (Ni) translocation in Ni
      hyperaccumulating plants. Here, we investigated its role in zinc (Zn)
      translocation in four accessions of the Zn hyperaccumulator, Noccaea
      caerulescens, using the related non-hyperaccumulator, Thlaspi arvense, as a
      reference. We compared the effects of exogenous histidine supply on Zn xylem
      loading, and of Zn-histidine complex formation on Zn uptake in energized
      tonoplast vesicles. The Zn distribution patterns over root tissues were also
      compared. Exogenous histidine supply enhanced Zn xylem loading in all the N.
      caerulescens accessions, but decreased it in T. arvense. Zn distribution patterns
      over root tissues were similar, apart from the accumulation in cortical and
      endodermal cells, which was much lower in N. caerulescens than in T. arvense. Zn
      uptake in energized tonoplast vesicles was inhibited significantly in N.
      caerulescens, but not affected significantly in T. arvense, when Zn was supplied
      in combination with histidine in a 1:2 molar ratio. Histidine-mediated Zn xylem
      loading seems to be a species-wide character in N. caerulescens. It may well have
      evolved as a component trait of the hyperaccumulation machinery for Zn, rather
      than for Ni.

PMID- 24750121
TI  - Discrimination between surgical and nonsurgical nuclear cataracts based on ROC
      analysis.
AB  - PURPOSE: The aim of this article is to propose a quantitative methodology for
      determining a criterion to discriminate the nonsurgical nuclear cataract from the
      surgical one taking into account objective measures of intraocular scattering in
      patients with good visual acuity (>0.6). METHODS: Two groups of subjects were
      taken into account: a control group and a group with nuclear cataracts. At a
      first stage, eyes belonging to the cataract group were classified into
      "nonsurgical" and "surgical" cataracts by ophthalmologists at their clinical
      settings. At a second stage a double-pass instrument was also used to determine
      the objective scatter index (OSI) at the laboratory. Receiver operating
      characteristic (ROC) curves were used to analyze OSI values to determine a value
      able to separate between nonsurgical and surgical cataracts. RESULTS: We obtained
      statistically significant differences among the control and both nuclear cataract
      groups (p < 0.05). ROC curves determined an OSI criterion level (of 2.1) to
      suggest surgery in nuclear cataracts with an area under curve of 0.83, i.e. with
      80% of sensitivity and 80% of specificity. CONCLUSIONS: ROC analysis allows
      separating both groups of nuclear cataract, and we determined a value of OSI in
      nuclear cataract quantification for surgery.

PMID- 24750122
TI  - Interleukin-7 is decreased and maybe plays a pro-inflammatory function in primary
      immune thrombocytopenia.
AB  - Primary immune thrombocytopenia (ITP) is an autoimmune disease with many immune
      dysfunctions, including over-proliferation and apoptosis resistance of auto
      reactive lymphocytes. This study aimed to determine the effects of interleukin
      (IL)-7 on the cytokine production and survival of peripheral blood mononuclear
      cells and bone marrow mononuclear cells from ITP patients. We found that the
      plasma IL-7 levels in peripheral blood from ITP patients were lower than that of
      the normal controls, and it had positive correlation with platelet counts.
      However, the levels of IL-7 did not change in bone marrow serum of ITP patients
      compared with that of normal controls. The result of further stimulation
      experiments in vitro showed that IL-7 up-regulated the apoptosis of autologous
      platelets, promoted the proliferation and secretion of interferon-gamma, tumor
      necrosis factor-alpha as well as IL-10 of lymphocyte both from peripheral blood
      and bone marrow. As the role of IL-7 in apoptosis-resistance and stimulation of
      pro-inflammatory cytokines, we speculated that decreased IL-7 in peripheral
      blood, maybe, is a consequence of the negative feedback of the pro-inflammatory
      function in ITP patients. 

PMID- 24750123
TI  - Abstracts of the Canadian Conference on Medical Education, 25-29 april 2014,
      Ottawa, Canada.

PMID- 24750124
TI  - High electrical conductivity in Ni3(2,3,6,7,10,11-hexaiminotriphenylene)2, a
      semiconducting metal-organic graphene analogue.
AB  - Reaction of 2,3,6,7,10,11-hexaaminotriphenylene with Ni(2+) in aqueous NH3
      solution under aerobic conditions produces Ni3(HITP)2 (HITP = 2,3,6,7,10,11
      hexaiminotriphenylene), a new two-dimensional metal-organic framework (MOF). The
      new material can be isolated as a highly conductive black powder or dark blue
      violet films. Two-probe and van der Pauw electrical measurements reveal bulk
      (pellet) and surface (film) conductivity values of 2 and 40 S.cm(-1),
      respectively, both records for MOFs and among the best for any coordination
      polymer. 

PMID- 24750125
TI  - Differentiation and healthy family functioning of Koreans in South Korea, South
      Koreans in the United States, and White Americans.
AB  - Inconsistent results have been found in prior research on the Bowen Family
      Systems Theory concept of differentiation of self and its application to
      individuals, couples, and families of different cultural backgrounds. In this
      regard, this study examined the impact of differentiation of self on healthy
      family functioning, family communication, and family satisfaction with 277
      participants including South Koreans living in South Korea, South Korean-born
      citizens living in the United States, and White Americans living in the United
      States. Multigroup confirmatory factor analysis identified the measurement
      invariance of a differentiation scale (DSI-R) used for the three study groups. An
      analysis of covariance (ANCOVA) found significant differences between White
      Americans and South Koreans with regard to the level of differentiation. Results
      of multigroup structural equation modeling (SEM) analyses found a significant
      association between differentiation of self and healthy family functioning across
      the three groups with the American group having significantly higher
      differentiation than the two South Korean groups." Implications for clinical
      practice and future research are discussed. 

PMID- 24750126
TI  - Combined estimating equation approaches for semiparametric transformation models
      with length-biased survival data.
AB  - Survival data are subject to length-biased sampling when the survival times are
      left-truncated and the underlying truncation time random variable is uniformly
      distributed. Substantial efficiency gains can be achieved by incorporating the
      information about the truncation time distribution in the estimation procedure
      [Wang (1989) Journal of the American Statistical Association 84, 742-748; Wang
      (1996) Biometrika 83, 343-354]. Under the semiparametric transformation models,
      the maximum likelihood method is expected to be fully efficient, yet it is
      difficult to implement because the full likelihood depends on the nonparametric
      component in a complicated way. Moreover, its asymptotic properties have not been
      established. In this article, we extend the martingale estimating equation
      approach [Chen et al. (2002) Biometrika 89, 659-668; Kim et al. (2013) Journal of
      the American Statistical Association 108, 217-227] and the pseudo-partial
      likelihood approach [Severini and Wong (1992) The Annals of Statistics 4, 1768
      1802; Zucker (2005) Journal of the American Statistical Association 100, 1264
      1277] for semiparametric transformation models with right-censored data to handle
      left-truncated and right-censored data. In the same spirit of the composite
      likelihood method [Huang and Qin (2012) Journal of the American Statistical
      Association 107, 946-957], we further construct another set of unbiased
      estimating equations by exploiting the special probability structure of length
      biased sampling. Thus the number of estimating equations exceeds the number of
      parameters, and efficiency gains can be achieved by solving a simple combination
      of these estimating equations. The proposed methods are easy to implement as they
      do not require additional programming efforts. Moreover, they are shown to be
      consistent and asymptotically normally distributed. A data analysis of a dementia
      study illustrates the methods.

PMID- 24750127
TI  - Does a cyclopropane ring enhance the electronic communication in dumbbell-type
      C60 dimers?
AB  - Two C60 dumbbell molecules have been synthesized containing either cyclopropane
      or pyrrolidine rings connecting two fullerenes to a central fluorene core. A
      combination of spectroscopic techniques reveals that the cyclopropane dumbbell
      possesses better electronic communication between the fullerenes and the
      fluorene. This observation is underpinned by DFT transport calculations, which
      show that the cyclopropane dumbbell gives a higher calculated single-molecule
      conductance, a result of an energetically lower-lying LUMO level that extends
      deeper into the backbone. This strengthens the idea that cyclopropane behaves as
      a quasi-double bond. 

PMID- 24750128
TI  - Sequential therapy with alternating short courses of R-CHOP (rituximab,
      cyclophosphamide, doxorubicin, vincristine, prednisone) and R-FM (rituximab,
      fludarabine, mitoxantrone) followed by autologous stem cell transplantation
      results in long term remission in advanced follicular lymphoma.

PMID- 24750129
TI  - Dating and Hooking Up in College: Meeting Contexts, Sex, and Variation by Gender,
      Partner's Gender, and Class Standing.
AB  - This study examined 13,976 dates and 12,068 hookup encounters at 22 colleges in
      the United States reported by students surveyed between 2005 and 2011 in the
      Online College Social Life Survey (OCSLS) to determine differences between dates
      and hookups in partner meeting context and sex during the encounter. Students
      most often met date and hookup partners through institutional settings or bars
      and parties, with approximately two-thirds of partners met in these venues. Those
      who had fewer potential partners on campus (women) were less likely to find
      partners in campus locations and less likely to find male sexual or dating
      partners but more likely to date women. Men and women engaging in same-sex
      encounters had higher rates of meeting partners through Internet sources. Hookups
      were associated with partners met in bars, parties, nightclubs, and college
      dormitories, and were twice as likely as dates to include sex. Students were more
      likely to go on dates with partners met on the Internet, which we theorize is a
      result of low levels of trust associated with that context. Patterns found are
      related to the association of meeting contexts with hookup scripts, risk and
      trust, and local partnering markets. 

PMID- 24750130
TI  - Novel role of glial syntaxin-1B in supporting neuronal survival.

PMID- 24750131
TI  - Is growth hormone treatment in children associated with weight gain?-
      longitudinal analysis of KIGS data.
AB  - OBJECTIVE: Growth hormone (GH) increases lean body mass and reduces fat mass.
      However, the long-term changes in weight status during growth hormone treatment,
      according to age and weight status at onset of treatment, have not previously
      been reported in large data sets. METHODS: Changes in BMI-SDS between starting GH
      treatment and attaining near adult height (NAH) were analysed in 2643 children
      with idiopathic GH deficiency (IGHD), 281 children small for gestational age
      (SGA), 1661 girls with Turner syndrome (TS), and 142 children with Prader-Willi
      syndrome (PWS) in the KIGS database. RESULTS: BMI-SDS increased significantly
      between onset of GH treatment and NAH (IGHD:+0.29, SGA:+0.69, TS:+0.48) except in
      PWS (-0.02). These increases were greater in children with younger age at onset
      of GH treatment (significant in all indications) and with lower doses of GH
      treatment (significant in IGHD & TS) in multiple linear regression analyses also
      including gender, duration of GH treatment, BMI-SDS and height-SDS at onset of
      treatment, and birth weight-SDS. Obese children at onset of GH treatment
      decreased their BMI-SDS, while underweight and normal weight children at onset of
      GH treatment increased their BMI-SDS independently of GH treatment indication.
      CONCLUSIONS: Long-term GH treatment was associated with changes in weight status,
      which were beneficial for underweight and obese children independent of the
      indication for GH. However, the increase in BMI-SDS in normal weight children
      treated with GH needs to be investigated in future prospective longitudinal
      studies to analyse whether this represents an increase of fat mass, lean body
      mass or both.

PMID- 24750132
TI  - Generalized fixed drug eruption in a child due to trimethoprim/sulfamethoxazole.

PMID- 24750133
TI  - The KIT D816V allele burden predicts survival in patients with mastocytosis and
      correlates with the WHO type of the disease.
AB  - KIT D816V is present in a majority of patients with systemic mastocytosis (SM).
      We determined the KIT D816V allele burden by quantitative real-time PCR in bone
      marrow and peripheral blood of 105 patients with mastocytosis. KIT D816V was
      detected in 92/105 patients (88%). Significant differences in the median allele
      burden were observed between disease subgroups: cutaneous mastocytosis (0.042%),
      indolent SM (0.285%), smoldering SM (5.991%), aggressive SM (9.346%), and SM with
      associated hematologic non-mast cell lineage disease (3.761%) (P < 0.001). The
      KIT D816V burden also correlated with serum tryptase (R = 0.5, P < 0.005) but not
      with mast cell infiltration in bone marrow or mediator symptoms. Moreover, the
      allele burden was of prognostic significance regarding survival (P < 0.01).
      Patients responding to cytoreductive therapy showed a significant decrease in KIT
      D816V (P < 0.05). To conclude, the KIT D816V burden correlates with the variant
      of mastocytosis, predicts survival, and is a valuable follow-up parameter in SM.

PMID- 24750134
TI  - Giant volume change of active gels under continuous flow.
AB  - While living systems have developed highly efficient ways to convert chemical
      energy (e.g., ATP hydrolysis) to mechanical motion (e.g., movement of muscle), it
      remains a challenge to build muscle-like biomimetic systems to generate
      mechanical force directly from chemical reactions. Here we show that a continuous
      flow of reactant solution leads to by far the largest volume change to date in
      autonomous active gels driven by the Belousov-Zhabotinsky reaction. These results
      demonstrate that microfluidics offers a useful and facile experimental approach
      to optimize the conditions (e.g., fabrication methods, counterions, flow rates,
      concentrations of reagents) for chemomechanical transduction in active materials.
      This work thus provides much needed insights and methods for the development of
      chemomechanically active systems based on combining soft materials and
      microfluidic systems. 

PMID- 24750135
TI  - Hydroxide-bridged cubane complexes of nickel(II) and cadmium(II): magnetic, EPR,
      and unusual dynamic properties.
AB  - The reactions of M(ClO4)2.xH2O (M = Ni(II) or Cd(II)) and m-bis[bis(1
      pyrazolyl)methyl]benzene (Lm) in the presence of triethylamine lead to the
      formation of hydroxide-bridged cubane compounds of the formula [M4(MU3-OH)4(MU
      Lm)2(solvent)4](ClO4)4, where solvent = dimethylformamide, water, acetone. In the
      solid state the metal centers are in an octahedral coordination environment, two
      sites are occupied by pyrazolyl nitrogens from Lm, three sites are occupied by
      bridging hydroxides, and one site contains a weakly coordinated solvent molecule.
      A series of multinuclear, two-dimensional and variable-temperature NMR
      experiments showed that the cadmium(II) compound in acetonitrile-d3 has C2
      symmetry and undergoes an unusual dynamic process at higher temperatures
      (DeltaGLm? = 15.8 +/- 0.8 kcal/mol at 25  degrees C) that equilibrates the
      pyrazolyl rings, the hydroxide hydrogens, and cadmium(II) centers. The proposed
      mechanism for this process combines two motions in the semirigid Lm ligand termed
      the "Columbia Twist and Flip:" twisting of the pyrazolyl rings along the Cpz
      Cmethine bond and 180 degrees  ring flip of the phenylene spacer along the CPh
      Cmethine bond. This dynamic process was also followed using the spin saturation
      method, as was the exchange of the hydroxide hydrogens with the trace water
      present in acetonitrile-d3. The nickel(II) analogue, as shown by magnetic
      susceptibility and electron paramagnetic resonance measurements, has an S = 4
      ground state, and the nickel(II) centers are ferromagnetically coupled with
      strongly nonaxial zero-field splitting parameters. Depending on the Ni-O-Ni
      angles two types of interactions are observed: J1 = 9.1 cm(-1) (97.9 to 99.5
      degrees ) and J2 = 2.1 cm(-1) (from 100.3 to 101.5 degrees ). "Broken symmetry"
      density functional theory calculations performed on a model of the nickel(II)
      compound support these observations.

PMID- 24750136
TI  - A comparative analysis of MAPK pathway hallmark alterations in pilocytic
      astrocytomas: age-related and mutually exclusive. [corrected].

PMID- 24750138
TI  - Automated analysis of delayed emesis in the telemetered ferret: detection of
      synergistic effects of aprepitant and ondansetron.
AB  - Nausea and vomiting are common side effects of cancer chemotherapy. We have
      previously described a model in the ferret where delayed emesis can be measured
      automatically using telemetry. This study was designed to examine the sensitivity
      of this automated emesis model for detecting moderate and/or additive
      pharmacological effects by investigating low-dose effects of aprepitant alone or
      in combination with ondansetron. Ferrets implanted with telemetry devices (Data
      Sciences International) were orally treated with aprepitant (0.03 mg/kg) and/or
      ondansetron (0.3 mg/kg) and then challenged with cisplatin (8 mg/kg, i.p.).
      Abdominal pressure was recorded in unrestrained animals from 18 to 72 h post
      challenge, and the pressure signals were automatically analyzed using adapted
      software (Emka Technologies). Ondansetron administered alone 1 h before cisplatin
      challenge had no significant effects on the delayed emesis phase. Once-daily
      treatment with aprepitant (2 h before cisplatin and then 24 and 48 h after
      cisplatin challenge) slightly reduced the total number of emetic events (-32%,
      NS). When administered together, aprepitant and ondansetron exhibited synergistic
      effects on delayed-phase emesis. The combined treatment markedly and
      significantly decreased the mean number of emetic events recorded between 24 and
      54 h after cisplatin dosing (-75%, P < 0.05) and the total number of emetic
      events (-56%, p < 0.05). Our results demonstrate that the automated cisplatin
      induced emesis model in the ferret is sensitive enough to detect the synergistic
      effects of aprepitant and ondansetron in combination, creating new and important
      perspectives for the evaluation of combined therapy in the reduction of side
      effects of cancer chemotherapy.

PMID- 24750137
TI  - The Arabidopsis thaliana mitogen-activated protein kinases MPK3 and MPK6 target a
      subclass of 'VQ-motif'-containing proteins to regulate immune responses.
AB  - Mitogen-activated protein kinase (MAPK) cascades play key roles in plant immune
      signalling, and elucidating their regulatory functions requires the
      identification of the pathway-specific substrates. We used yeast two-hybrid
      interaction screens, in vitro kinase assays and mass spectrometry-based
      phosphosite mapping to study a family of MAPK substrates. Site-directed
      mutagenesis and promoter-reporter fusion studies were performed to evaluate the
      impact of substrate phosphorylation on downstream signalling. A subset of the
      Arabidopsis thaliana VQ-motif-containing proteins (VQPs) were phosphorylated by
      the MAPKs MPK3 and MPK6, and renamed MPK3/6-targeted VQPs (MVQs). When plant
      protoplasts (expressing these MVQs) were treated with the flagellin-derived
      peptide flg22, several MVQs were destabilized in vivo. The MVQs interact with
      specific WRKY transcription factors. Detailed analysis of a representative member
      of the MVQ subset, MVQ1, indicated a negative role in WRKY-mediated defence gene
      expression - with mutation of the VQ-motif abrogating WRKY binding and causing
      mis-regulation of defence gene expression. We postulate the existence of a
      variety of WRKY-VQP-containing transcriptional regulatory protein complexes that
      depend on spatio-temporal VQP and WRKY expression patterns. Defence gene
      transcription can be modulated by changing the composition of these complexes -
      in part - through MAPK-mediated VQP degradation. 

PMID- 24750139
TI  - Asymptomatic traumatic diaphragmatic hernia discovered during an aortic valve
      replacement.
AB  - Asymptomatic traumatic diaphragmatic hernia, which presents in an adult, is an
      extremely rare entity. We discuss the management of a 63-year-old male with an
      asymptomatic traumatic diaphragmatic hernia discovered during aortic valve
      replacement.

PMID- 24750140
TI  - Preface. Role in the development of endoscopic diagnosis and treatment.

PMID- 24750141
TI  - Present status of endoscopy, therapeutic endoscopy and the endoscopy training
      system in Indonesia.
AB  - Recently, Indonesia was ranked as the fourth most populous country in the world.
      Based on 2012 data, 85000 general practitioners and 25000 specialists are in
      service around the country. Gastrointestinal (GI) disease remains the most common
      finding in daily practise, in both outpatient and inpatient settings, and ranks
      fifth in causing mortality in Indonesia. Management of patients with GI disease
      involves all health-care levels with the main portion in primary health care.
      Some are managed by specialists in secondary health care or are referred to
      tertiary health care. GI endoscopy is one of the main diagnostic and therapeutic
      modalities in the management of GI disease. Development of GI endoscopy in
      Indonesia started before World War II and, today, many GI endoscopy procedures
      are conducted in Indonesia, both diagnostic and therapeutic. Based on August 2013
      data, there are 515 GI endoscopists in Indonesia. Most GI endoscopists are
      competent in carrying out basic endoscopy procedures, whereas only a few carry
      out advanced endoscopy procedures, including therapeutic endoscopy. Recently, the
      GI endoscopy training system in Indonesia consists of basic GI endoscopy training
      of 3-6 months held at 10 GI endoscopy training centers. GI endoscopy training is
      also eligible as part of a fellowship program of consultant gastroenterologists
      held at six accredited fellowship centers in Indonesia. Indonesian Society for
      Digestive Endoscopy in collaboration with GI endoscopy training centers in
      Indonesia and overseas has been working to increase quality and number of GI
      endoscopists, covering both basic and advanced GI endoscopy procedures.

PMID- 24750142
TI  - Advances in diagnostic endoscopy for duodenal, including ampullary, adenoma.
AB  - Currently, the strategy for real-time endoscopic diagnosis of duodenal, including
      ampullary, adenoma is still unclear. In the era of high-definition and
      magnification endoscopy, using this modality for the detection and diagnosis of
      these neoplasms is very challenging for endoscopists. Over the past 10 years,
      many instruments have been developed to improve the detection rate of duodenal
      and ampullary polyps and to distinguish between adenoma and non-adenoma. The
      present review will focus on these novel methods and their usefulness in the
      diagnosis of ampullary and non-ampullary adenoma. 

PMID- 24750143
TI  - Diagnostic algorithm of magnifying endoscopy with narrow band imaging for
      superficial non-ampullary duodenal epithelial tumors.
AB  - BACKGROUND AND AIM: A novel diagnostic algorithm for magnifying endoscopy with
      narrow band imaging (ME-NBI) for superficial non-ampullary duodenal epithelial
      tumors (SNADET) is needed because of diagnostic difficulties. METHODS: In the
      present study, ME-NBI images taken prior to endoscopic treatment were
      retrospectively analyzed to investigate the relationship between ME-NBI findings
      and pathological findings. Lesions displaying a single surface pattern were
      classified as monotype, and those displaying multiple surface patterns as mixed
      type. Surface pattern was classified as preserved, micrified, or absent. In
      addition, vascular pattern was classified as absent, network, intrastructural
      vascular (ISV), or unclassified. RESULTS: According to the revised Vienna
      classification, 100% (23/23) of mixed-type lesions were category 4/5 tumors,
      whereas approximately 50% (10/23) of monotype lesions were category 3 tumors. In
      the monotype lesions, the probability of category 4/5 tumor was 100% (2/2) in
      lesions with an unclassified vascular pattern, 64.3% (9/14) in lesions with an
      ISV pattern, 33.3% (1/3) in lesions with an absent pattern, and 25.0% (1/4) in
      lesions with a network pattern. CONCLUSION: These findings suggest the
      possibility of developing an effective diagnostic algorithm for ME-NBI for SNADET
      by determining their surface pattern and vascular pattern.

PMID- 24750144
TI  - Endoscopic diagnosis of superficial non-ampullary duodenal epithelial tumors in
      Japan: Multicenter case series.
AB  - BACKGROUND AND AIM: To verify the current status in Japan on endoscopic diagnosis
      of superficial non-ampullary duodenal epithelial tumors (SNADET) by a multicenter
      case series through a questionnaire survey. METHODS: Nine endoscopists and a
      surgeon responded to a questionnaire on endoscopic diagnosis of SNADET. The
      subjects of this survey were histologically confirmed SNADET that were
      endoscopically or surgically resected from 2007 to 2012. This survey collected
      data of 364 patients with 396 SNADET. RESULTS: Of the 396 SNADET, 121 were
      histologically diagnosed as low-grade dysplasia (LGD), 112 as high-grade
      dysplasia (HGD), and 163 as superficial adenocarcinoma (SAC) including 153
      mucosal carcinomas and 10 submucosal carcinomas. Total number of SNADET increased
      from 125 in the first half to 271 in the second half of the survey period.
      Compared to LGD, a significantly greater number of HGD or SAC was found in the
      tumors having a diameter >5 mm as well as solitary or predominantly red color.
      Preoperative endoscopic diagnosis indicated significantly higher sensitivity and
      accuracy and significantly lower specificity for HGD or SAC of final histology
      than preoperative biopsy. Ten submucosal carcinomas had 0-I or 0-IIa+IIc
      macroscopic-type tumors with red color. CONCLUSIONS: This multicenter case series
      study suggested that the number of resected SNADET is dramatically increasing in
      Japan. Tumor diameter >5 mm and red color seemed to be signs for tumors of HGD or
      SAC. Preoperative endoscopy may provide a more reliable diagnosis of final
      histology of HGD or SAC than preoperative biopsy. Further studies are warranted
      for establishing endoscopic features of submucosal carcinoma.

PMID- 24750145
TI  - Duodenal adenomatosis in Japanese patients with familial adenomatous polyposis.
AB  - Duodenal adenomatosis is the most frequent extracolonic manifestation of familial
      adenomatous polyposis (FAP), and duodenal cancer has been assumed to be the
      second most significant cause of death in patients with the disease. To stratify
      the risk of duodenal cancer, Spigelman's classification was proposed for the
      staging of duodenal adenomatosis. According to Western guidelines, patients with
      stage IV of the classification are candidates for prophylactic duodenectomy.
      Since our institutional experience disclosed only 2% of duodenal or ampullary
      cancers among 130 patients with FAP, and because most duodenal adenomatosis
      remains unchanged under endoscopic surveillance, it seems likely that aggressive
      endoscopic or surgical removal is unnecessary for most FAP patients with duodenal
      adenomatosis. In the present article, we demonstrate our data and present our
      strategy for duodenal adenomatosis of FAP. 

PMID- 24750146
TI  - Method and timing of resection of superficial non-ampullary duodenal epithelial
      tumors.
AB  - BACKGROUND AND AIM: Non-ampullary duodenal epithelial tumors (NADET) are rare,
      and there is no consensus regarding treatment indications and methods for
      superficial lesions. Records of patients with NADET over a 10-year period were
      reviewed to clarify the present state of clinical management of superficial
      NADET. METHODS: Data related to clinicopathological characteristics, selection of
      treatment, and outcomes were collected and analyzed. RESULTS: Of 95 lesions, 73
      were either adenoma or mucosal or submucosal invasive cancers. Half of the
      patients with a biopsy diagnosis of low-grade adenoma were followed up without
      treatment. Results of endoscopic resection (ER), including endoscopic mucosal
      resection (EMR) or endoscopic submucosal dissection (ESD) for patients with high
      grade adenoma (HGA) or cancer showed a high en bloc resection rate. However, the
      risk of perforation was high among ESD cases. Surgery was done for patients with
      a diagnosis of cT1a or cT1b cancer, of which half underwent local resection. An
      upgrade in pathology between preoperative biopsy and final pathology was observed
      in 11/13 lesions with a biopsy diagnosis of HGA. CONCLUSIONS: Superficial NADET,
      including HGA, should be treated endoscopically or surgically. For lesions with
      no risk of metastasis, local resection by EMR may be reasonable or clinically
      sufficient regarding the high complication rate of ESD. However, surgery remains
      a standard treatment for lesions that are technically impossible to remove by ER.

PMID- 24750147
TI  - Endoscopic tissue shielding with polyglycolic acid sheets, fibrin glue and clips
      to prevent delayed perforation after duodenal endoscopic resection.
AB  - The incidence of delayed perforation after endoscopic resection for superficial
      non-ampullary duodenal epithelial tumors is extremely high. Endoscopic tissue
      shielding with polyglycolic acid (PGA) sheets and fibrin glue is a promising
      method to prevent delayed perforation after endoscopic resection in the duodenum.
      However, we often encounter difficulty when covering an artificial ulcer with PGA
      sheets after endoscopic resection. We report three cases of postoperative ulcers
      covered by PGA sheets, fibrin glue, and clips. 

PMID- 24750148
TI  - Endoscopic tissue shielding method with polyglycolic acid sheets and fibrin glue
      to prevent delayed perforation after duodenal endoscopic submucosal dissection.
AB  - Delayed perforation after duodenal endoscopic submucosal dissection (ESD) occurs
      at a high rate because the duodenal wall is very thin and the artificial ulcer
      after resection is exposed to bile and pancreatic juice. We investigated the
      application of the combination of a polyglycolic acid (PGA) sheet and fibrin
      glue. PGA sheets comprise materials widely used in surgery for absorbable thread.
      Fibrin glue is a heated blood product and is used for hemostasis during
      operations. We developed a combined method using both materials. We have used
      this method in two cases. One case involved an elevated lesion located in the
      lower duodenal angle of the duodenum. The other involved an elevated lesion in
      the second portion of the duodenum. About 1 week after ESD, the PGA sheets
      remained covering the ulcer and delayed perforation did not occur. We were able
      to easily carry out this method for several parts of the duodenum. This method
      may be helpful for the prevention of delayed perforation after duodenal ESD. 

PMID- 24750149
TI  - Therapeutic outcomes of endoscopic resection for superficial non-ampullary
      duodenal tumor.
AB  - BACKGROUND AND AIM: Endoscopic resection (ER) is widely used as a minimally
      invasive therapy to remove superficial non-ampullary duodenal tumor (SNADT).
      However, the indication criteria have not yet been clearly determined. At our
      institute, ER is done only for SNADT measuring <= 20 mm. We report our findings
      on the therapeutic outcomes of ER of SNADT. METHODS: We carried out ER in 47
      patients with SNADT. Indication criteria for ER included a lesion suspected as
      high-grade dysplasia or mucosal cancer and measuring <= 20 mm. The ER methods
      used to carry out en bloc resection were endoscopic mucosal resection (EMR: 17
      lesions) or endoscopic submucosal dissection (ESD: 30 lesions). We then analyzed
      the therapeutic outcomes between them. RESULTS: There were no significant
      differences between the EMR and ESD groups with regard to age, sex, location of
      the lesion, and histology. The most frequent gross types resected by EMR and ESD
      were 0-IIa and 0-IIc, respectively (P=0.004). Median procedure time was
      significantly longer in ESD than in EMR, 79.5 and 9 min, respectively (P<0.001).
      R0 resection was achieved in 10 cases by EMR (59%) and in 27 cases by ESD (90%)
      (P=0.017). No complications occurred in cases that underwent EMR, but immediate
      and delayed perforations occurred in three patients who underwent ESD, although
      this difference was not statistically significant (P=0.467). CONCLUSION: Using
      our indication criteria, which limited lesion size to <= 20 mm, satisfactory
      therapeutic outcomes of ER of SNADT were obtained.

PMID- 24750150
TI  - Surgical management of superficial non-ampullary duodenal tumors.
AB  - BACKGROUND AND AIM: We present our experiences with the so-called 'limited
      resections' such as transduodenal excision and local full-thickness resection for
      superficial non-ampullary duodenal tumors (SNADT). The optimal surgical
      management for SNADT is also discussed. METHODS: Six patients with SNADT
      (adenoma, n=1; mucosal carcinomas, n=2; submucosal carcinoma, n=1; carcinoids,
      n=2) were included in this study. Four patients underwent transduodenal excision,
      one local full-thickness resection, and one laparoscopy-assisted endoscopic full
      thickness resection as a modification of local full-thickness resection. RESULTS:
      All patients were successfully treated by these limited resections without any
      adverse events. CONCLUSIONS: Surgical resection is the treatment of choice for
      SNADT not amenable to endoscopic resection in terms of technical and/or
      oncological reasons. However, the optimal surgical management for SNADT remains
      controversial because of the complexity of the relevant anatomy of the duodenum,
      its rarity, the not well-known incidence of nodal metastasis, and the wide
      spectrum of pathologies that can be encountered.

PMID- 24750151
TI  - Current management of diminutive colorectal polyps in Taiwan.
AB  - The majority of polyps detected during colonoscopy are diminutive polyps, for
      which the cost of pathological analysis is substantial. In our analysis of a
      screening cohort of 10737 subjects undergoing screening colonoscopy, a total of
      15877 neoplastic lesions were detected, of which 10816 (68.1%) were diminutive
      lesions. Of those diminutive lesions, 90 (0.83%) had a villous component, 14
      (0.1%) had high-grade dysplasia, and none had invasive cancer. Only 1.3% of
      patients were advised to decrease their surveillance interval because of
      unfavorable histology. Laws regulating medical practice, uncertainty regarding
      the accuracy of endoscopic diagnosis of diminutive polyps outside of academic
      centers, and the relatively low cost of pathological analysis are among the
      barriers to adopting a 'resect and discard' practice in Taiwan.

PMID- 24750152
TI  - Evaluation of the effectiveness of color intensity analysis using a second
      generation autofluorescence imaging system for diminutive colorectal polyp
      differentiation.
AB  - BACKGROUND AND AIM: We previously reported the effectiveness of color tone
      intensity analysis using autofluorescence imaging (AFI) for distinguishing
      between colorectal neoplastic and non-neoplastic lesions. Moreover, a second
      generation AFI system has become commercially available in Japan. In the present
      study, we assessed the effectiveness of color tone intensity analysis using a
      second-generation AFI system for evaluating diminutive colorectal lesions.
      METHODS: We retrospectively reviewed the cases of 35 consecutive patients with
      101 diminutive colorectal lesions that were examined using a second-generation
      AFI system and resected at the Jikei University Hospital. We estimated the mean
      green-to-red (G/R) ratio - obtained by dividing the green color tone intensity by
      the red color tone intensity - of the lesions and compared the values of the
      neoplastic and non-neoplastic lesions. We also assessed the sensitivity,
      specificity, positive predictive value (PPV), and negative predictive value (NPV)
      of the AFI system for neoplastic lesion identification. RESULTS: The mean G/R
      ratios of the non-neoplastic and neoplastic lesions were 1.06 and 0.87,
      respectively; the mean G/R ratio significantly differed between the neoplastic
      and non-neoplastic lesions. Using the second-generation AFI system, neoplastic
      lesions were identified with a sensitivity, specificity, PPV, and NPV of 94.2%,
      91.8%, 92.5%, and 93.8%, respectively. CONCLUSION: Color intensity analysis of
      diminutive colorectal polyps using the second generation AFI system could
      effectively distinguish between neoplastic and non-neoplastic lesions.

PMID- 24750153
TI  - Development and progression of colorectal cancer based on follow-up analysis.
AB  - Elucidating the pathway of colorectal cancer development and progression can lead
      to identification of lesions that must be treated appropriately. The aim of the
      present review was to summarize the development and progression of colorectal
      cancer based on radiological and endoscopic follow-up analyses. These studies
      revealed several characteristic findings, including that initial morphology with
      progression to advanced cancer was most commonly 0-Is, followed by 0-IIa. Based
      on the doubling time, 0-Ip grew slowly in comparison with other morphologies. The
      observation period from adenomas measuring <10 mm to intramucosal cancers was
      more than 5 years. This makes it difficult to draw any accurate conclusions about
      the natural history of colorectal cancer based on follow-up observation alone and
      it is difficult to exclude the selection bias because of the difficulty of follow
      up for flat and depressed tumor. However, the only reliable way to elucidate the
      natural history is to accumulate cases.

PMID- 24750154
TI  - Endoscopic features and management of diminutive colorectal submucosal invasive
      carcinoma.
AB  - BACKGROUND AND AIM: The vast majority of diminutive (~5 mm) colorectal tumors
      consist of a very low prevalence of advanced neoplasia, and a predict-resect-and
      discard policy has been proposed recently in Western countries. The histology of
      some diminutive colorectal tumors reveals carcinoma, not adenoma, although the
      frequency is relatively low. Clarifying the endoscopic features of diminutive
      submucosal invasive colorectal carcinoma (CRC) during colonoscopy is important
      for managing diminutive lesions. METHODS: A total of 111 cases of submucosal
      invasive CRC <= 10 mm were analyzed. The incidence of submucosal invasion in
      early CRC per gross type, size, location, pit pattern diagnosis, and rate of
      lymph node (LN) metastasis was evaluated. RESULTS: In diminutive tumors, the
      overall submucosal invasion rate in early CRC was 9.6%; however, depressed tumors
      had a significantly higher frequency of submucosal invasion than protruded or
      flat elevated tumors. There were no significant differences in the distribution
      of submucosal invasive CRC between the diminutive tumors and those that were 6-10
      mm. The pit pattern diagnosis of diminutive submucosal invasive CRC was type VI
      pit pattern in all cases. Each case of submucosal invasive CRC was completely
      resected by en bloc endoscopic resection, and there were no cases of LN
      metastasis. CONCLUSION: Diminutive tumors with depression have a high frequency
      of submucosal invasive CRC and an initial indication for endoscopic resection.

PMID- 24750155
TI  - Natural history of diminutive colorectal polyps: long-term prospective
      observation by colonoscopy.
AB  - BACKGROUND AND AIM: Endoscopic removal of colorectal adenomatous polyps
      effectively prevents cancer. However, the treatment strategy for diminutive
      polyps (diameter <= 5 mm) remains controversial. Understanding the natural
      history of diminutive polyps is a prerequisite to their effective management. We
      prospectively examined the natural history of diminutive polyps by long-term
      surveillance colonoscopy. METHODS: A total of 207 polyps detected in 112 patients
      from December 1991 through March 2002 were studied. To avoid potential effects on
      size and morphological characteristics, all polyps were selected randomly and
      were followed without biopsy. Polyp size was estimated by comparing the lesion
      with the diameter of a biopsy forceps. RESULTS: Mean follow up was 7.8 years (SD,
      4.8; range, 1.0-18.6; median, 7.5; interquartile range 3.4-11.2). Twenty-four
      polyps were resected endoscopically, and the histopathological diagnosis was
      mucosal high-grade neoplasia (Category 4) for one polyp, and mucosal low-grade
      neoplasia (Category 3) for 23 polyps. Mean linear size of the polyps was 3.2 mm
      (SD, 1.0; range, 1.3-5.0) at initial colonoscopy and 3.8 mm (SD 1.6; range 1.3
      10.0) at final colonoscopy (P<0.01). Left-sided polyps showed a higher growth
      rate than right-sided polyps, and a type IIIL2 pit pattern was associated with a
      lower growth rate than a type IIIL1 pattern. CONCLUSION: We clarified the natural
      history of diminutive polyps by long-term follow-up colonoscopy. The benign
      course of diminutive polyps should be considered in the design of treatment
      strategies.

PMID- 24750156
TI  - Proposal of a new 'resect and discard' strategy using magnifying narrow band
      imaging: pilot study of diagnostic accuracy.
AB  - BACKGROUND AND AIM: A 'resect and discard' strategy using non-magnifying narrow
      band imaging (N-NBI) has been proposed for reducing screening colonoscopy costs,
      but it does not take into consideration advanced histology and magnifying NBI (M
      NBI) that can potentially further improve the 'resect and discard' strategy. We
      conducted a pilot study to investigate the feasibility of M-NBI for the new
      'resect and discard' strategy with consideration for advanced histology. METHODS:
      The present study involved 63 patients. For each polyp, optical diagnosis was
      independently made using N-NBI and M-NBI, a decision (discard or send for
      pathology) was made based on the M-NBI findings, and histological and optical
      diagnosis results were compared. RESULTS: Sensitivity, specificity and accuracy
      (95% confidence interval) of M-NBI for lesions with advanced histology were 1.00
      (0.36-1.00), 0.92 (0.91-0.92) and 0.92 (0.90-0.92), respectively. Whereas the
      management of 86% of small polyps could be decided without formal histopathology,
      lesions with advanced histology were not discarded using M-NBI. The diagnostic
      accuracy of M-NBI in distinguishing neoplastic from non-neoplastic lesions was
      higher than that of N-NBI. CONCLUSIONS: We propose a new resect and discard
      strategy with advanced histology using M-NBI that is a promising strategy to
      reduce the costs of histopathology and to minimize the risk of discarding
      important lesions.

PMID- 24750157
TI  - Cold polypectomy techniques for diminutive polyps in the colorectum.
AB  - Adequate colonoscopic polypectomy is a very important intervention for the
      prevention of colorectal cancer progression during screening and surveillance
      colonoscopy. Whereas various techniques are used for the removal of diminutive
      polyps, including cold biopsy forceps, hot biopsy forceps, hot snare, and cold
      snare, hot polypectomy techniques with electrocautery have been associated with
      an increased risk of electrocautery-related complications, including immediate
      and/or delayed bleeding or perforation. In contrast, recent studies have found a
      polypectomy technique without electrocautery, so-called cold polypectomy, to be a
      safer and more efficacious technique. The present article discusses the use of
      cold polypectomy techniques and describes how cold biopsy forceps polypectomy
      using jumbo biopsy forceps designed with a greater capacity for removing larger
      tissue samples, and cold snare polypectomy, are adequate for removing diminutive
      polyps completely and safely and shorten withdrawal time of the colonoscopy
      procedure. 

PMID- 24750159
TI  - Current status of endoscopic retrograde cholangiopancreatography in patients with
      surgically altered anatomy in Japan: questionnaire survey and important
      discussion points at Endoscopic Forum Japan 2013.
AB  - BACKGROUND AND AIM: Endoscopic retrograde cholangiopancreatography (ERCP) in
      patients with surgically altered anatomy is still challenging. We aimed to
      clarify the current status of ERCP in Japan in patients with surgically altered
      anatomy. METHODS: Questionnaire survey was conducted in 2012 at 11 participating
      facilities regarding ERCP in patients with surgically altered anatomy. RESULTS: A
      total of 490 ERCP procedures were carried out in 273 patients with surgically
      altered anatomy. The breakdown of surgical procedures was as follows: Roux-en-Y
      (R-Y) reconstruction (n=154 [31.4%]), pancreaticoduodenectomy (PD) (n=136
      [27.8%]), hepaticojejunostomy (n=103 [21.0%]), liver transplantation (n=20
      [4.1%]), Billroth II reconstruction (n=69 [14.1%]), and interposition after total
      gastrectomy (n=8 [1.6%]). The overall success rate of reaching the target site
      was 91.8% (450 of 490 ERCP procedures). According to reconstructive surgical
      procedures, the target site was reached in 138 of 154 procedures (89.6%) for R-Y
      reconstruction, 129 of 136 procedures (94.8%) for PD, 89 of 103 procedures
      (86.4%) for hepaticojejunostomy, 18 of 20 procedures (90.0%) for liver
      transplantation, 68 of 69 procedures (98.6%) for Billroth II reconstruction, and
      eight of eight procedures (100%) for interposition after total gastrectomy.
      CONCLUSIONS: The success rate of reaching the target site was high in patients
      with Billroth II reconstruction and low in patients with hepaticojejunostomy.
      Although the success rate of endoscopic insertion for ERCP in patients with
      surgically altered anatomy was high, there are still cases in which it is
      difficult to achieve technical success.

PMID- 24750158
TI  - Current status and future perspectives of endoscopic diagnosis and treatment of
      diminutive colorectal polyps.
AB  - During colonoscopy, small and diminutive colorectal polyps are commonly
      encountered. It is estimated that at least one adenomatous polyp is detected in
      almost half of all patients undergoing screening colonoscopy. In contrast, the
      'predict, resect, and discard' strategy for diminutive and small colorectal
      polyps is a current topic especially in Western countries. 'Is this an acceptable
      policy in Japan?' Herein, we report the results of a questionnaire survey with
      regard to the management of diminutive colorectal polyps, including the thoughts
      of Japanese endoscopists regarding the 'predict, resect, and discard' strategy.
      At the moment, we propose that this strategy should be used by skilled
      endoscopists only. 

PMID- 24750160
TI  - Ampullary intervention for bile duct stones in patients with surgically altered
      anatomy.
AB  - Transpapillary endoscopic treatment is a standard technique for the treatment of
      bile duct stones. This technique includes biliary cannulation, ampullary
      interventions such as endoscopic sphincterotomy (EST) and endoscopic papillary
      balloon dilation (EPBD), and stone removal. In patients with Roux-en-Y
      anastomosis, the transpapillary approach using an ordinary scope has been
      challenging. A recently developed single-/double-balloon enteroscope enables
      therapeutic endoscopic retrograde cholangiopancreatography to be carried out in
      such cases. EST using a balloon enteroscope is often difficult to carry out as a
      result of restriction of scope maneuverability or inadequate direction of the
      accessory. Although EPBD is easy to carry out for any anatomy, large or multiple
      stones are difficult to remove by EPBD only because of insufficient opening of
      Vater's papilla. Endoscopic papillary large-balloon dilation following EST is
      reported to be useful for the treatment of large and/or multiple stones. This
      technique is also useful for the treatment of bile duct stones in patients with
      Roux-en-Y anastomosis. 

PMID- 24750161
TI  - Endoscopic bile duct and/or pancreatic duct cannulation technique for patients
      with surgically altered gastrointestinal anatomy.
AB  - There are two major hurdles to carrying out endoscopic retrograde
      cholangiopancreatography (ERCP) in patients with altered gastrointestinal anatomy
      (Billroth II gastrectomy [B-II], Roux-en-Y anastomosis [R-Y] etc.), post
      pancreatoduodenectomy or post-choledochojejunostomy. These are: (i) the
      endoscopic approach to the afferent loop, blind end, and the site of bilio
      pancreatic anastomosis; and (ii) bile duct and/or pancreatic duct cannulation.
      Balloon-assisted enteroscopy (BAE) became available in recent years and is now
      being actively used to overcome the first hurdle and, at least, the success rate
      has improved. However, room for improvement still remains in regards to the
      second hurdle (i.e. the success rate of cannulation of the bile duct and/or
      pancreatic duct), and there has been a desire for the development of dedicated
      devices (ERCP catheters, hoods etc.) and for improvement in the functionality of
      the enteroscopes etc. In the present review, we explain the basic procedure for
      bile duct and/or pancreatic duct cannulation with conventional endoscopes and
      BAE, and modifications of the basic procedure. 

PMID- 24750162
TI  - Impact of instrument channel diameter on therapeutic endoscopic retrograde
      cholangiography using balloon-assisted enteroscopy.
AB  - BACKGROUND AND AIM: In therapeutic endoscopic retrograde cholangiography (ERC)
      using a balloon-assisted enteroscope, each instrument insertion requires a long
      time, which prolongs the duration of the procedure. We conducted a retrospective
      single-center study to compare instrument insertability of a double-balloon
      enteroscope (DBE) with a 2.8-mm instrument channel diameter and a prototype short
      single-balloon enteroscope (SBE) with a 3.2-mm instrument channel diameter.
      METHODS: We used a stop-watch to measure instrument insertion time from the
      instrument channel port to the tip of the enteroscope when balloon-assisted ERC
      was done. The instruments were divided into two groups (outer diameter larger or
      smaller than 2 mm). Lengths from the instrument channel port to the tip of the
      DBE (EI-530B; FUJIFILM, Tokyo, Japan) and the prototype SBE (SIF-Y0004-V01;
      Olympus Medical Systems, Tokyo, Japan) were identical (1680 mm). ERC using DBE
      was carried out in four cases, as was ERC using SBE. RESULTS: There was a
      significant time difference (P= 0.001) when using instruments whose outer
      diameters were >2 mm (53.5 +/- 19.0 s in DBE vs 28.4 +/- 8.4 s in SBE).
      CONCLUSION: The prototype SBE with a 3.2-mm channel demonstrated not only that
      many types of instrument can be used, but also that the time required to insert
      instruments may be shorter than that with DBE with a 2.8-mm channel.

PMID- 24750163
TI  - Short double-balloon enteroscopy is feasible and effective for endoscopic
      retrograde cholangiopancreatography in patients with surgically altered
      gastrointestinal anatomy.
AB  - Endoscopic retrograde cholangiopancreatography (ERCP) for patients with digestive
      tract reconstruction is a difficult procedure from an anatomical point of view. A
      short-type double-balloon enteroscope has a 2.8-mm working channel and a 152-cm
      working length, and its advantage is that it can accommodate most conventional
      devices for ERCP. Although the shorter length compared with the long-type balloon
      assisted enteroscope (BAE) was suspected of making it difficult or impossible to
      reach the blind end, in fact, the success rate of reaching the blind end with the
      short type is similar to that with the long- type BAE. In addition, the success
      rate of ERCP-related procedures with the short type is satisfactory. However, it
      remains controversial as to which BAE is more suitable for this procedure.
      Further randomized controlled trials by high-volume centers are warranted. 

PMID- 24750164
TI  - Single- and double-balloon enteroscopy-assisted endoscopic retrograde
      cholangiopancreatography in patients with Roux-en-Y plus hepaticojejunostomy
      anastomosis and Whipple resection.
AB  - BACKGROUND AND AIM: In patients with Roux-en-Y hepaticojejunostomy (HJ with R-Y)
      and Whipple resection, endoscopic retrograde cholangiopancreatography (ERCP) can
      be challenging. We report our experience with ERCP using balloon-assisted
      enteroscopy (BAE) (BAE-ERCP) in patients with HJ with R-Y, and Whipple resection.
      METHODS: BAE-ERCP procedures were carried out in 62 patients (HJ with R-Y:Whipple
      resection=34:28). RESULTS: Overall, the rates of reaching the anastomosis were
      85.3% (29/34) in HJ with R-Y and 96.4% (27/28) in Whipple resection. In terms of
      HJ with R-Y, insertion success rate by standard single-balloon enteroscopy (SBE)
      was 89.3% (25/28). Insertion success rate by short BAE, including SBE and double
      balloon enteroscopy (DBE), was 50% (3/6). There was a statistically significant
      difference of insertion success rate between standard long BE and short BE
      (P=0.021). However, in the Whipple patients, insertion success rate by standard
      and short SBE was 93.8% (15/16) and 91.7% (11/12), respectively. Initial
      insertion success rate by short BAE in Whipple patients was significantly higher
      than in HJ with R-Y (91.7% vs 50%, P=0.045). Therapeutic interventions included
      dilation of anastomosis stricture, stone extraction, endoscopic mechanical
      lithotripsy, biliary stent placement, stent extraction, endoscopic nasobiliary
      drainage, direct cholangioscopy, and electrohydraulic lithotripsy. Our HJ with R
      Y series and Whipple series treatment success rate was 90% (18/20) and 95.0%
      (19/20), respectively. CONCLUSIONS: BAE-ERCP enabled ERCP to be carried out in
      patients with HJ. It is considered safe and feasible. Further experience and
      device improvement are needed.

PMID- 24750165
TI  - Post-endoscopic retrograde cholangiopancreatography pancreatitis caused by
      papillary large-balloon dilation of incidental intrapapillary fistula in Roux-en
      Y patients: lesson from a case.
AB  - Endoscopic papillary large-balloon dilation (EPLBD) has been popular worldwide
      for difficult stones. At the primary stage, EPLBD is done immediately after
      endoscopic sphincterotomy (ES) or after previous ES. Recently, several
      endoscopists have reported the feasibility and safety of EPLBD without ES and
      post-endoscopic retrograde cholangiopancreatography pancreatitis (PEP) as adverse
      events. Herein, we encountered a case of PEP in which EPLBD was carried out
      through a spontaneous fistula in the papillary roof, although there was no
      manipulation of the pancreatic duct. We learned a lesson from the present case in
      which possible PEP might occur during the procedure of EPLBD without ES. 

PMID- 24750166
TI  - Evaluation of endoscopic retrograde cholangiopancreatography using a newly
      developed short-type single-balloon endoscope in patients with altered
      gastrointestinal anatomy.
AB  - BACKGROUND AND AIM: Endoscopic approaches for pancreatobiliary diseases in
      patients with altered gastrointestinal anatomy had been impractical until the
      development of balloon-assisted endoscope (BAE) made it feasible. The aim of the
      present study was to evaluate the usefulness of a newly developed short-type
      single-balloon endoscope (s-SBE) for endoscopic retrograde
      cholangiopancreatography (ERCP) in patients with altered gastrointestinal
      anatomy. METHODS: From March 2013 to November 2013, s-SBE-assisted ERCP was done
      in our hospital in 26 postoperative patients who had surgically altered anatomy.
      We retrospectively evaluated the success rate of reaching the blind end, the mean
      time required to reach the blind end, the diagnostic success rate, the
      therapeutic success rate, the mean procedure time, and complications. RESULTS:
      The success rate of reaching the blind end was 92.3%. The mean time required to
      reach the blind end was 25.3 min. The diagnostic success rate was 91.7%. The
      diagnostic success rate for naive papilla was 75%. The mean procedure time was
      56.0 min. The success rate of overall s-SBE-assisted ERCP was 84.6%. The
      complication rate was 3.8%. CONCLUSION: Diagnostic and therapeutic ERCP using a
      newly developed s-SBE is sufficiently effective.

PMID- 24750167
TI  - Short-type and conventional single-balloon enteroscopes for endoscopic retrograde
      cholangiopancreatography in patients with surgically altered anatomy: single
      center experience.
AB  - BACKGROUND AND AIM: Endoscopic retrograde cholangiopancreatography (ERCP) is
      technically challenging in patients with Roux-en-Y anastomosis and Billroth-II
      anastomosis. Short-type single-balloon enteroscope (SBE) was developed to carry
      out ERCP in postoperative patients with a reconstructed intestine. It is useful
      because of its good rotational and straightening ability and the availability of
      various conventional ERCP accessories through the 3.2-mm working channel, and it
      has a water-jet channel. METHODS: In the present study, we compared outcomes
      between groups with short-type SBE and conventional SBE. RESULTS: With regard to
      reaching the blind end, mean time to reach the blind end, diagnostic success
      rate, therapeutic success rate, mean procedure time, and complication rate, there
      were no statistical differences between the two groups. CONCLUSION: The results
      suggest that both types of SBE are equally useful for ERCP in patients with a
      reconstructed intestine. Short-type SBE may be more preferable because of its
      good specification and maneuverability.

PMID- 24750168
TI  - Looking back over the third term of Endoscopy Forum Japan.

PMID- 24750169
TI  - Single electron transfer in radical ion and radical-mediated organic, materials
      and polymer synthesis.

PMID- 24750171
TI  - Combination of racial/ethnic and etiology/disease-specific factors is associated
      with lower survival following liver transplantation in African Americans: an
      analysis from UNOS/OPTN database.
AB  - Higher rates of hepatitis C virus (HCV) recurrence and lower response to HCV
      antiviral therapy contribute to the lower post-liver transplantation (LT)
      survival among African Americans with HCV. The current study aims to evaluate
      race/ethnicity-specific and etiology-specific factors contributing to lower post
      LT survival among African Americans in the USA. The 2002-2012 United Network for
      Organ Sharing registry was utilized to evaluate race/ethnicity-specific post-LT
      survival among patients with HCV, hepatocellular carcinoma (HCC), alcoholic liver
      disease (ALD), non-alcoholic steatohepatitis, and cryptogenic cirrhosis. From
      2002 to 2012, HCV was the leading indication for LT. While African Americans
      accounted for 9.5% of all LT during this period, they had the lowest overall and
      etiology-specific five-yr post-LT survival. On multivariate Cox proportional
      hazards modeling, African Americans had significantly lower post-LT survival
      compared with non-Hispanic whites among patients with HCV (HR, 1.30; 95% CI, 1.19
      1.41), HCC (HR, 1.49; 95% CI, 1.25-1.79), and ALD (HR, 1.52; 95% CI, 1.19-1.94).
      In conclusion, African Americans had the lowest post-LT survival among patients
      with HCV, HCC, and ALD. Race/ethnicity and the etiology of chronic liver disease
      were observed to have a combined detrimental effect leading to lower survival
      following LT in African Americans. 

PMID- 24750170
TI  - Does genetic distance between parental species influence outcomes of
      hybridization among coral reef butterflyfishes?
AB  - Christmas Island is located at the overlap of the Indian and Pacific Ocean marine
      provinces and is a hot spot for marine hybridization. Here, we evaluate the
      ecological framework and genetic consequences of hybridization between
      butterflyfishes Chaetodon guttatissimus and Chaetodon punctatofasciatus. Further,
      we compare our current findings to those from a previous study of hybridization
      between Chaetodon trifasciatus and Chaetodon lunulatus. For both species groups,
      habitat and dietary overlap between parental species facilitate frequent
      heterospecific encounters. Low abundance of potential mates promotes
      heterospecific pair formation and the breakdown of assortative mating. Despite
      similarities in ecological frameworks, the population genetic signatures of
      hybridization differ between the species groups. Mitochondrial and nuclear data
      from C. guttatissimus * C. punctatofasciatus (1% divergence at cyt b) show
      bidirectional maternal contributions and relatively high levels of introgression,
      both inside and outside the Christmas Island hybrid zone. In contrast, C.
      trifasciatus * C. lunulatus (5% cyt b divergence) exhibit unidirectional
      mitochondrial inheritance and almost no introgression. Back-crossing of hybrid C.
      guttatissimus * C. punctatofasciatus and parental genotypes may eventually
      confound species-specific signals within the hybrid zone. In contrast, hybrids of
      C. trifasciatus and C. lunulatus may coexist with and remain genetically distinct
      from the parents. Our results, and comparisons with hybridization studies in
      other reef fish families, indicate that genetic distance between hybridizing
      species may be a factor influencing outcomes of hybridization in reef fish, which
      is consistent with predictions from terrestrially derived hybridization theory. 

PMID- 24750172
TI  - Effects of a teenage pregnancy prevention program in KwaZulu-Natal, South Africa.
AB  - Researchers aimed to determine the effects of a teenage pregnancy (TP) prevention
      program for 816 high school students attending 16 KwaZulu-Natal, South African
      schools through a randomized control trial. Data were collected at baseline and
      at the 8-month follow-up in 2009. Results were calculated using multivariate
      analyses of program effects employing Mplus 6, and indicated significantly
      healthier attitudes, including intentions to abstain from sex whilst at school,
      plans to communicate with partners about teenage pregnancy, and increased reports
      of condom use. Researchers thus provide some support for the effectiveness of a
      TP prevention program that should be further strengthened in a comprehensive
      approach that includes schools and families. 

PMID- 24750174
TI  - Preclinic investigations accelerate decision-making, reduce delays in treatment
      and are highly popular with endocrinology patients and staff.
AB  - OBJECTIVE: Endocrine diagnosis relies on a thorough history, examination and
      confirmatory biochemical tests. Previously, in our unit, tests were performed
      after new patients attended clinic. We proposed that diagnosis and management
      would be improved if this system was inverted. DESIGN: Clinicians and chemical
      pathologists reviewed available guidance and local practice to determine the key
      tests to confirm or refute most common endocrine disorders. A system was
      developed for clinicians to categorize new referrals into diagnostic groups: for
      example, nodular thyroid disease or possible polycystic ovarian syndrome.
      Standard letters were developed and sent to patients explaining the requirement
      for tests to be performed prior to first hospital appointment. The letters and
      requests for investigation sets were standardized for each diagnostic group and
      generated via a one-click automated method. After one year, clinical outcomes
      were audited and patients and staff surveyed. RESULTS: The time from referral to
      confirming diagnosis and starting treatment was halved: mean 11.8-5.7 weeks (P <
      0.001). Acute patients were also discharged from clinic earlier: mean 17 to 10.3
      weeks (P < 0.005). Ninety four percent patients surveyed had their tests
      performed easily prior to attending their appointment. Hundred per cent of
      patients, 100% of hospital staff and 93% referring general practitioners who
      responded felt the system improved patient care and should continue. CONCLUSIONS:
      Performing investigations prior to new patient appointments is practical, popular
      with staff and patients and has dramatically improved our referral to treatment
      statistics by reducing delays prior to diagnosis. This system could be used as a
      model for other departments.

PMID- 24750175
TI  - Inappropriate reporting of clinical trials.

PMID- 24750173
TI  - IgE antibodies to alpha-gal in the general adult population: relationship with
      tick bites, atopy, and cat ownership.
AB  - BACKGROUND: The carbohydrate alpha-gal epitope is present in many animal
      proteins, including those of red meat and animal immunoglobulins, such as cat
      IgA. Systemic anaphylaxis to the alpha-gal epitope has recently been described.
      OBJECTIVE: To investigate and compare the prevalence of alpha-gal-specific (s)IgE
      and its associated factors in the general adult population from two separated
      (Northern and Southern) European regions (Denmark and Spain, respectively).
      METHODS: Cross-sectional study of 2297 and 444 randomly selected adults from 11
      municipalities in Denmark and one in Spain. Alpha-gal sIgE was assessed by
      ImmunoCAP to bovine thyroglobulin. Additional assessments included a panel of
      skin prick test (SPT) to common aeroallergens and epidemiological factors,
      including the history of tick bites in the Danish series. RESULTS: The prevalence
      of positive (>= 0.1 kUA /L) sIgE to alpha-gal was 5.5% and 8.1% in the Danish and
      Spanish series, respectively. The prevalence of sIgE >= 0.35 kUA /L was 1.8% and
      2.2% in Denmark and Spain, respectively. Alpha-gal sIgE positivity was associated
      with pet ownership in both series and, particularly, cat ownership (data
      available in the Danish series). Alpha-gal sIgE positivity was associated with
      atopy (SPT positivity) in both series, although it was not associated with SPT
      positivity to cat or dog dander. Alpha-gal sIgE positivity was strongly
      associated with a history of tick bites. CONCLUSIONS AND CLINICAL RELEVANCE: The
      prevalence of alpha-gal sIgE antibodies in these general adult European
      populations is similarly low. The presence of alpha-gal sIgE antibodies is
      associated with a history of tick bites, atopy, and cat ownership.

PMID- 24750176
TI  - A significant percentage of CD20-positive TILs correlates with poor prognosis in
      patients with primary cutaneous malignant melanoma.

PMID- 24750177
TI  - Comparing minimally invasive and proactive initial management of extremely
      preterm infants.
AB  - AIM: In 2005, we changed our minimally invasive departmental policy for infants
      born before 26 weeks of gestation to a proactive approach. This included
      structured guidelines as well as intubation and surfactant in the delivery room,
      if the parents agreed. The aim of this study was to evaluate the effect of this
      change of policy. METHOD: We compared the Ages and Stages Questionnaire (ASQ)
      scores, mortality rates and use of mechanical ventilation before (1999-2003) and
      after (2005-2011) the introduction of the new policy. RESULTS: Twenty-two per
      cent of 61 infants in the before group had an ASQ z-score of <-2 standard
      deviation at 18 months' corrected age, compared with 26% of 55 infants in the
      after group. Mortality decreased from 46% to 36% (p = 0.06) and the use of
      mechanical ventilation at any time during admission increased from 64% to 87% (p
      < 0.0001). CONCLUSION: We demonstrated that changing our policy to a proactive
      approach to the initial care of infants born before 26 weeks did not result in a
      major increase in psychomotor deficit. However, the use of mechanical ventilation
      increased significantly and survival tended to improve.

PMID- 24750178
TI  - Neuroprotective effects of enriched environment housing after transient global
      cerebral ischaemia are associated with the upregulation of insulin-like growth
      factor-1 signalling.
AB  - AIMS: Use of enriched environment (EE) housing has been shown to promote recovery
      from cerebral ischaemic injury but the underlying mechanisms of their beneficial
      effects remains unclear. Here we examined whether the beneficial effects of EE
      housing on ischaemia-induced neurodegeneration and cognitive impairment are
      associated with increased insulin-like growth factor-1 (IGF-1) signalling in the
      hippocampus. METHODS: Forty-two adult male Wistar rats were included in the study
      and received either ischaemia or sham surgery. Rats in each group were further
      randomized to either: EE or standard laboratory cage housing (control). Rats were
      placed in their assigned housing condition immediately after recovery from
      anaesthesia. Behavioural testing in the cued learning and discrimination learning
      tasks were conducted 2 weeks after ischaemia. Rats were euthanized after
      behavioural testing and the hippocampus was analysed for IGF-1 level, IGF-1
      receptor (IGF-1R) activation, protein kinase B (Akt) pathway activation, neurone
      loss and caspase 3 expression. RESULTS: Our data showed that EE housing: (1)
      mitigated ischaemia-induced neuronal loss; (2) attenuated ischaemia-induced
      increase in caspase 3 immunoreactivity in the hippocampus; (3) ameliorated
      ischaemia-induced cognitive impairments; and (4) increased IGF-1R activation and
      signalling through the Akt pathway after ischaemic injury. CONCLUSION:
      Ultimately, these findings suggest the possibility that IGF-1 signalling may be
      one of the underlying mechanisms involved in the beneficial effects of EE in
      optimizing recovery following cerebral ischaemic injury.

PMID- 24750179
TI  - QT dispersion in HIV-infected patients receiving combined antiretroviral therapy.
AB  - BACKGROUND: A higher prevalence of QT prolongation has been reported among human
      immunodeficiency virus (HIV)-infected patients. Previous studies have
      demonstrated that QT dispersion is a better predictor of serious ventricular
      tachyarrhythmia and cardiac mortality than corrected QT (QTc) interval. However,
      data of QT dispersion in HIV-infected patients receiving a combined
      antiretroviral therapy (cART) is limited. We sought to assess QTc interval and QT
      dispersion in HIV-infected patients receiving cART. The association between QT
      parameters and heart rate variability (HRV) was also examined. METHODS: Ninety
      one HIV-infected patients receiving cART (male = 33, mean age = 44 +/- 10 years)
      and 70 HIV-seronegative subjects (male = 25, mean age = 44 +/- 8 years) were
      enrolled in the study. In a resting 12-lead electrocardiogram, QT interval was
      measured by the tangent method in all leads with well-defined T waves. The QT
      dispersion was defined as the difference between maximum and minimum QTc
      intervals in any of 12 leads. RESULTS: The baseline characteristics were not
      different between the two groups. We demonstrated the significantly longer mean
      QTc interval (420 +/- 21 vs. 409 +/- 21 ms, P < 0.001), and greater QT dispersion
      in HIV-infected group compared to the control group (85 +/- 29 vs. 55 +/- 23 ms,
      P < 0.001). Among the HIV-infected patients, those who had lower CD4 lymphocyte
      count (<350 cells/mm(3)) tended to have greater QT dispersion (92 +/- 28 vs. 81
      +/- 29 ms, P = 0.098). There were no associations between QT parameters and
      either HRV or cART regimens. CONCLUSIONS: HIV-infected patients receiving cART
      were associated with prolonged QTc interval and increased QT dispersion,
      independent of autonomic dysfunction and antiretroviral drugs, which may have led
      to the potentially higher risk of ventricular arrhythmia and cardiac mortality.

PMID- 24750180
TI  - Left ventricular assists device insertion via small right axillary incision in a
      pediatric patient.
AB  - We report the use of a right axillary skin incision to institute a ventricle
      assist device support in a two-year-old 14 kg male with fulminant myocarditis.
      The ease of conversion to a long-term support, avoidance of a sternotomy, and a
      less visible incision made this approach an attractive option in this group of
      sick patients.

PMID- 24750181
TI  - Behaviour-related DRD4 polymorphisms in invasive bird populations.
AB  - It has been suggested that individual behavioural traits influence the potential
      to successfully colonize new areas. Identifying the genetic basis of behavioural
      variation in invasive species thus represents an important step towards
      understanding the evolutionary potential of the invader. Here, we sequenced a
      candidate region for neophilic/neophobic and activity behaviour - the complete
      exon 3 of the DRD4 gene - in 100 Yellow-crowned bishops (Euplectes afer) from two
      invasive populations in Spain and Portugal. The same birds were scored twice for
      activity behaviour while exposed to novel objects (battery or slice of apple) in
      captivity. Response to novel objects was repeatable (r = 0.41) within
      individuals. We identified two synonymous DRD4 SNPs that explained on average
      between 11% and 15% of the phenotypic variance in both populations, indicating a
      clear genetic component to the neophilic/neophobic/activity personality axis in
      this species. This consistently high estimated effect size was mainly due to the
      repeated measurement design, which excludes part of the within-individual
      nongenetic variance in the response to different novel objects. We suggest that
      the alternative alleles of these SNPs are likely introduced from the original
      population and maintained by weak or antagonistic selection during different
      stages of the invasion process. The identified genetic variants have not only the
      potential to serve as genetic markers of the neophobic/neophilic/activity
      personality axis, but may also help to understand the evolution of behaviour in
      these invasive bird populations.

PMID- 24750182
TI  - The effects of low arched feet on foot rotation during gait in children with Down
      syndrome.
AB  - BACKGROUND: In children with Down syndrome (DS) hypotonia and ligament laxity are
      characteristic features which cause a number of orthopaedic issues, such as flat
      foot. The aim of this study was to determine if children with flat foot are
      characterised by an accentuated external foot rotation during walking. METHOD:
      Fifty-five children with DS and 15 typically developing children recruited as
      control group were assessed using three-dimensional gait analysis, using an
      optoelectronic system, force platforms and video recording. Parameters related to
      foot rotation were identified and calculated and the participants' foot
      morphology was assessed using the arch index. RESULTS: Data obtained in this
      study showed that while DS children without flat foot displayed the foot position
      on the transverse plane globally close to controls during the whole gait cycle,
      the DS children with flat foot were characterised by higher extra-rotation of the
      foot in comparison with those without flat foot and controls. CONCLUSIONS: Our
      results suggest that the presence of flatfoot lead the children with DS to extra
      rotate their feet more than the children without flat foot. From a clinical point
      of view, these results could enhance the rehabilitative programmes in DS.

PMID- 24750183
TI  - Loneliness and suicidal ideation in drug-using college students.
AB  - The college years are marked by social changes and behavioral experimentation
      which may increase risk of suicidal ideation. We propose a novel pathway for the
      development of suicidal thoughts between two established suicide risk factors,
      loneliness and drug use, which have not been examined in a nonclinical sample.
      Data were collected from 207 undergraduate drug-using students at a large
      southeastern university. As hypothesized, suicidal ideation was positively
      correlated with both loneliness (r = .40) and drug use (r = .29). After
      controlling for several demographic variables, social desirability, and anxiety
      sensitivity, drug use was tested as a potential mediator in the loneliness
      suicidal ideation link using a single-mediator model. Results indicated a
      significant indirect (mediated) effect of loneliness on suicidal ideation via
      drug use (ab = 0.09, 95% CI: 0.02-0.18), suggesting that loneliness may
      contribute to suicidal ideation through increased drug use among college
      students. Identification of and intervention with students reporting loneliness
      and drug use may be a promising suicide prevention strategy on college campuses. 

PMID- 24750184
TI  - Metabolic and hormonal contributors to survival in the participants of the Mataro
      Ageing Study at 8 years follow-up.
AB  - OBJECTIVE: Ageing is a physiological process that may be influenced by genetic
      factors as well as metabolic and hormonal determinants. The aim was to describe
      metabolic and hormonal factors related to survival in the cohort of non
      institutionalized people aged >70 years old of the Mataro Ageing Study. DESIGN
      AND METHODS: 313 individuals were included and followed-up during 8 years.
      Metabolic syndrome (MS) parameters by International Diabetes Federation and ATP
      III as well as hormonal factors (TSH, free-T4, growth hormone, IGF-I, ghrelin,
      cortisol, dehydroepiandrosterone -DHEA-, DHEAs, testosterone, SHBG, estradiol,
      estrone, cortisol/DHEA and cortisol/DHEAs) were studied and their relationship
      with survival was assessed. RESULTS: At 8 year of follow-up, 96 out of 313
      subjects (30.7%) died. No association between MS and its components and survival
      was found. However, when abdominal perimeter was analyzed according to
      distribution in quartiles and categorized by gender, the lowest and highest
      quartile showed higher mortality (P = 0.009; waist circumference (WC) between 98
      102 cm in men and 95-102 cm in women were associated to lower mortality). In men,
      IGF-I, estrone, cortisol/DHEA ratio and cortisol/DHEAs ratio were lower in
      survivors, and in women, growth hormone and ghrelin were higher in survivors and
      cortisol/DHEAs ratio was lower. When Cox regression was performed for survival
      analysis of the whole cohort (adjusting by age, gender, tobacco consumption and
      WC, cortisol (B = 0.036, P = 0.033), estrone (B = 0.014, P = 0.004) and
      cortisol/DHEA ratio (B = 0.018, P = 0.008) were significantly associated to
      mortality. Sequential adjustments including additionally in the model Lawton
      scale, MiniNutritional Assessment and MCE showed significant association to
      estrone (P = 0.018). CONCLUSIONS: Waist circumference in a U-shaped relationship,
      together with hormonal factors (adrenal steroids and somatotropic axis)
      influenced survival in individuals participating in Mataro Ageing Study.

PMID- 24750185
TI  - Induced nitric oxide synthetase and peroxiredoxin expression in intramucosal
      poorly differentiated gastric cancer of young patients.
AB  - To investigate the relationship between oxidative stress and gastric
      carcinogenesis of poorly differentiated adenocarcinoma in young patients, we
      analyzed the surgically resected specimens of 22 young patients (21-30 years) and
      29 older patients (41-72 years) with intramucosal gastric cancer of the poorly
      differentiated type. We used immunohistochemical staining to evaluate the
      expression of 8-hydroxydeoxyguanosine (8OHdG), induced nitric oxide synthetase
      (iNOS), and antioxidant enzymes (thioredoxin [TRX] and peroxiredoxin [PRDX1, 2
      and 3]). We assessed these proteins in the cancer, noncancerous gastric foveolar
      epithelium and noncancerous mucosal neck. In both the young and older patient
      groups, the 8OHdG and TRX expressions were gradually increased in cancer cells
      compared with the noncancerous foveolar epithelial cells and the noncancerous
      mucosal neck cells (P < 0.001). Although the iNOS and PRDXs expressions were
      increased in the noncancerous mucosal neck cells compared with the noncancerous
      foveolar epithelial cells, regardless of age (P < 0.001), the iNOS and PRDX2
      expression in the cancer cells were significantly reduced in the young patients
      compared with the older patients (P < 0.001, P < 0.05). In conclusion, the
      reduced expression of iNOS or PRDX2 may play an important role in the
      carcinogenesis of gastric cancer associated with Helicobacter pylori-induced
      chronic active gastritis in young patients. 

PMID- 24750186
TI  - Prognostic significance of single isolated cells with decreased E-cadherin
      expression in pseudomyxoma peritonei.
AB  - Pseudomyxoma peritonei (PMP) cases can be classified into the prognosis-related
      subtypes of disseminated peritoneal adenomucinosis (DPAM) and peritoneal mucinous
      carcinomatosis (PMCA). To investigate the mechanisms of mucinous invasion and the
      differing prognoses of these two subtypes, we examined the expression levels of
      proteins involved in cellular adhesion and invasion, including E-cadherin,
      vimentin, beta-catenin, and S100A4, in single isolated tumor cells (SICs) and
      cohesive cellular strips within mucin pools isolated from DPAM (n = 31) and PMCA
      (n = 21) patients. In both PMCA and DPAM cases, SICs showed a complete loss of E
      cadherin expression, whereas cells in cohesive cellular clusters retained E
      cadherin expression. The frequency of high numbers of SICs (>8) in PMCA cases was
      significantly greater than that in DPAM cases (86% and 26%, respectively) and was
      correlated with poor progression-free survival (P = 0.019) in a univariate
      analysis. In both PMP subtypes, strong vimentin expression was identified in most
      of the SICs but not the cohesive cellular strips. The relatively slow progression
      of DPAM may be attributable to the smaller number of SICs that lack E-cadherin
      expression and have increased vimentin expression, whereas the rapid progression
      of PMCA may be due to larger numbers of these SICs. 

PMID- 24750187
TI  - Aortic squamous metaplasia in a patient with aortoesophageal fistula secondary to
      thoracic aortic aneurysm: an autopsy case.
AB  - Aortoesophageal fistula (AEF) is highly lethal. A 74-year-old man presented with
      hematemesis and consciousness loss. He had a long-term history of hypertension
      and gout. Computed tomography revealed an aneurysm of the distal descending
      thoracic aorta, which was treated by insertion of an aortic stent graft. After 24
      days of stenting, endoscopic examination revealed an AEF. After 6 months of
      stenting, he died owing to mediastinitis. On autopsy, macroscopically, we found a
      4 * 2.5-cm, oval, well-circumscribed AEF. We identified squamous epithelium in
      the area surrounding the AEF that covered the thoracic aorta inner cavity.
      Immunohistochemical analysis revealed that the squamous epithelium in the
      thoracic aorta was positive for p63 and 34betaE12. In conclusion, we encountered
      a long-term AEF case with aortic squamous metaplasia. To the best of our
      knowledge, human aortic metaplasia has never been reported. In the present case,
      aortic squamous metaplasia retained continuity with the esophageal squamous
      epithelium; therefore, the migration of the squamous epithelium through the AEF
      may have been induced by aortic erosion. 

PMID- 24750189
TI  - Oncocytic adrenocortical neoplasm arising from adrenal rest in the broad ligament
      of the uterus.
AB  - Oncocytic adrenocortical neoplasm is characterized by abundant eosinophilic
      cytoplasm containing mitochondria, occasional nuclear atypia and diffuse growth
      pattern. Oncocytic adrenocortical neoplasm arising in adrenal rest is, however,
      extremely rare. We report a case of oncocytic adrenocortical neoplasm arising in
      adrenal rest of the broad ligament with associated marked lipomatous metaplasia.
      A well circumscribed tumor was accidentally detected in the pelvic cavity of a 29
      year old Japanese woman, adjacent to the broad ligament of the uterus. The tumor
      was composed of large eosinophilic cells associated with diffuse growth pattern
      and abundant mature adipose tissue admixed with foci of clear cells. Both
      steroidgenic factor 1 (SF-1) and alpha-inhibin were immunohistochemically
      positive in tumor cells. Abundant mitochondria detected by immunohistochemical
      and electron microscopic examination confirmed the diagnosis of oncocytic
      adrenocortical neoplasm. The absence of necrosis, capsular and vascular invasion
      as well as the low mitotic index indicated the benign potential of this tumor.
      The tumor cells were also positive for dehydroepiandrosteron-sulfotransferase
      (DHEA-ST), 17beta-hydroxysteroid dehydrogenase type 5 (17beta-HSD5), 3beta
      hydroxysteroid dehydrogenase (3beta-HSD) and steroid 17alpha-hydroxylase (P450
      c17), suggesting a possible production of testosterone of this tumor. This is the
      first reported case of oncocytic adrenocortical adenoma arising in adrenal rest
      of the broad ligament. 

PMID- 24750190
TI  - Congenital peribronchial myofibroblastic tumor.

PMID- 24750188
TI  - Colonic low-grade endometrial stromal sarcoma and orthotopic endometrial stromal
      tumor with limited infiltration sharing the JAZF1-SUZ12 gene fusion.
AB  - Endometrial stromal tumors (ESTs) are composed of cells resembling endometrial
      stroma, and are divided into benign and malignant types based on morphology.
      Endometrial stromal nodule (ESN) is a benign localized tumor, and endometrial
      stromal sarcoma (ESS) is an infiltrative and potentially metastatic neoplasm. A
      series of genetic aberrations contribute to pathological diagnosis of ESTs. At
      present, subsets of ESN and ESS-low grade (ESS-LG) are characterized as JAZF1
      SUZ12/JJAZ1 gene fusion. The ESTs that show higher grade atypia but lack nuclear
      pleomorphism include YWHAE-FAM22 ESS. Here we report an unusual case of ESTs.
      Sudden colonic perforation occurred to the patient, and emergency surgery was
      performed. Pathological findings suggested metastatic ESS. Thorough medical
      examination of the genital organs detected a 1 cm-sized well-demarcated uterine
      tumor. Microscopically, the tumor lacked infiltrative features, conforming to the
      definition of ESN. Both lesions demonstrated identical cytology and shared JAZF1
      SUZ12 gene fusion. Endometriosis was not found in any areas of the resected
      organs, strongly suggesting that the uterine orthotopic tumor metastasized. The
      current case uncovered the problems of differential diagnosis between ESN and ESS
      LG. We demonstrate detailed pathological features of the two lesions, and discuss
      the possibility of orthotopic EST with limited infiltration to develop into ESS
      LG. 

PMID- 24750191
TI  - Periodic acid Schiff staining-positive spermatocytic seminoma.

PMID- 24750192
TI  - Hybrid myxoinflammatory fibroblastic sarcoma/hemosiderotic fibrolipomatous tumor
      of the ankle following repeated trauma.

PMID- 24750193
TI  - Early aggressive nutrition enhances language development in very low-birthweight
      infants.
AB  - BACKGROUND: Inadequate nutrition in very-low-birthweight (VLBW) infants is known
      to be associated with growth failure and poor neurological outcomes. We aimed to
      investigate the association of early aggressive protein and energy intakes with
      weight gain and 18-month neurodevelopmental outcomes in VLBW infants. METHODS: A
      total of 90 infants among 129 infants who survived to discharge were included and
      divided into two groups (early aggressive nutrition [n = 52] vs conventional
      nutrition [n = 38]). Clinical findings were compared between the two groups and
      daily protein and energy intakes were collected for the first 4 weeks of life.
      Multiple regression analyses tested the association between weekly protein or
      energy intakes and the result of each category of the Denver Developmental
      Screening Test II at 18 months' corrected age or weight gain. RESULTS: The early
      aggressive nutrition group had higher rates of normal language development and
      lower rates of growth failure (<10th percentile) at both 40 weeks' and 18 months'
      corrected age compared to the conventional nutrition group. After controlling for
      the confounding variables, higher first week protein and energy intakes each
      independently contributed to normal language development (odds ratio [95%
      confidence interval]; 9.4 [1.8-49.6] per 1 g/kg of protein increase and 1.7 [1.1
      2.8] per 10 kcal/kg of energy increase). Higher first-week protein intake was
      associated with a higher weight at 40 weeks' corrected age (r = 0.41, P = 0.005).
      CONCLUSIONS: This study demonstrates the importance of the protein and energy
      intakes in VLBW infants in the first week of life not only for growth but also
      for better language development.

PMID- 24750194
TI  - Effective maybe, but is it cost-effective? A reply.

PMID- 24750195
TI  - Serum liver-type fatty acid-binding protein predicts recovery of graft function
      after kidney transplantation from donors after cardiac death.
AB  - Kidneys procured by donation after cardiac death (DCD) may increase the donor
      pool but are associated with high incidence of delayed graft function (DGF).
      Urinary liver-type fatty acid-binding protein (L-FABP) level is an early
      biomarker of renal injury after kidney transplantation (KTx); however, its
      utility is limited in DGF cases owing to urine sample unavailability. We examined
      whether serum L-FABP level predicts functional recovery of transplanted DCD
      kidneys. Consecutive patients undergoing KTx from living related donors (LD),
      brain-dead donors (BD), or DCD were retrospectively enrolled. Serum L-FABP levels
      were measured from samples collected before and after KTx. Serum L-FABP decreased
      rapidly in patients with immediate function, slowly in DGF patients, and somewhat
      increased in DGF patients requiring hemodialysis (HD) for >1 wk. Receiver
      operating characteristic curve analysis demonstrated that DGF was predicted with
      84% sensitivity (SE) and 86% specificity (SP) at cutoff of 9.0 ng/mL on post
      operative day (POD) 1 and 68% SE and 90% SP at 6.0 on POD 2. DGF >7 d was
      predicted with 83% SE and 78% SP at 11.0 on POD 1 and 67% SE and 78% SP at 6.5 on
      POD 2. Serum L-FABP levels may predict graft recovery and need for HD after DCD
      KTx.

PMID- 24750196
TI  - Conservation and divergence of gene expression plasticity following c. 140
      million years of evolution in lodgepole pine (Pinus contorta) and interior spruce
      (Picea glauca*Picea engelmannii).
AB  - Species respond to environmental stress through a combination of genetic
      adaptation and phenotypic plasticity, both of which may be important for survival
      in the face of climatic change. By characterizing the molecular basis of plastic
      responses and comparing patterns among species, it is possible to identify how
      such traits evolve. Here, we used de novo transcriptome assembly and RNAseq to
      explore how patterns of gene expression differ in response to temperature,
      moisture, and light regime treatments in lodgepole pine (Pinus contorta) and
      interior spruce (a natural hybrid population of Picea glauca and Picea
      engelmannii). We found wide evidence for an effect of treatment on expression
      within each species, with 6413 and 11,658 differentially expressed genes
      identified in spruce and pine, respectively. Comparing patterns of expression
      among these species, we found that 74% of all orthologs with differential
      expression had a pattern that was conserved in both species, despite 140 million
      yr of evolution. We also found that the specific treatments driving expression
      patterns differed between genes with conserved versus diverged patterns of
      expression. We conclude that natural selection has probably played a role in
      shaping plastic responses to environment in these species.

PMID- 24750197
TI  - Effects of types of ventilation system on indoor particle concentrations in
      residential buildings.
AB  - The objective of this study was to quantify the influence of ventilation systems
      on indoor particle concentrations in residential buildings. Fifteen occupied,
      single-family apartments were selected from three sites. The three sites have
      three different ventilation systems: unbalanced mechanical ventilation, balanced
      mechanical ventilation, and natural ventilation. Field measurements were
      conducted between April and June 2012, when outdoor air temperatures were
      comfortable. Number concentrations of particles, PM2.5 and CO2 , were
      continuously measured both outdoors and indoors. In the apartments with natural
      ventilation, I/O ratios of particle number concentrations ranged from 0.56 to
      0.72 for submicron particles, and from 0.25 to 0.60 for particles larger than 1.0
      MUm. The daily average indoor particle concentration decreased to 50% below the
      outdoor level for submicron particles and 25% below the outdoor level for fine
      particles, when the apartments were mechanically ventilated. The two mechanical
      ventilation systems reduced the I/O ratios by 26% for submicron particles and 65%
      for fine particles compared with the natural ventilation. These results showed
      that mechanical ventilation can reduce exposure to outdoor particles in
      residential buildings. PRACTICAL IMPLICATIONS: Results of this study confirm that
      mechanical ventilation with filtration can significantly reduce indoor particle
      levels compared with natural ventilation. The I/O ratios of particles
      substantially varied at the naturally ventilated apartments because of the
      influence of variable window opening conditions and unsteadiness of wind flow on
      the penetration of outdoor air particles. For better prediction of the exposure
      to outdoor particles in naturally ventilated residential buildings, it is
      important to understand the penetration of outdoor particles with variable window
      opening conditions.

PMID- 24750198
TI  - Subjective sleepiness is a sensitive indicator of insufficient sleep and impaired
      waking function.
AB  - The main consequence of insufficient sleep is sleepiness. While measures of sleep
      latency, continuous encephalographical/electro-oculographical (EEG/EOG) recording
      and performance tests are useful indicators of sleepiness in the laboratory and
      clinic, they are not easily implemented in large, real-life field studies.
      Subjective ratings of sleepiness, which are easily applied and unobtrusive, are
      an alternative, but whether they measure sleepiness sensitively, reliably and
      validly remains uncertain. This review brings together research relevant to these
      issues. It is focused on the Karolinska Sleepiness Scale (KSS), which is a nine
      point Likert-type scale. The diurnal pattern of sleepiness is U-shaped, with high
      KSS values in the morning and late evening, and with great stability across
      years. KSS values increase sensitively during acute total and repeated partial
      sleep deprivation and night work, including night driving. The effect sizes range
      between 1.5 and 3. The relation to driving performance or EEG/EOG indicators of
      sleepiness is highly significant, strongly curvilinear and consistent across
      individuals. High (>6) KSS values are associated particularly with impaired
      driving performance and sleep intrusions in the EEG. KSS values are also
      increased in many clinical conditions such as sleep apnea, depression and
      burnout. The context has a strong influence on KSS ratings. Thus, physical
      activity, social interaction and light exposure will reduce KSS values by 1-2
      units. In contrast, time-on-task in a monotonous context will increase KSS values
      by 1-2 units. In summary, subjective ratings of sleepiness as described here is
      as sensitive and valid an indicator of sleepiness as objective measures, and
      particularly suitable for field studies. 

PMID- 24750199
TI  - Gastrointesintal: rare congenital abnormality of the duodenum: intraluminal
      duodenal diverticulum.

PMID- 24750200
TI  - Gastrointestinal: radiofrequency ablation in the management of refractory gastric
      antral vascular ectasia.

PMID- 24750201
TI  - Gastrointestinal: bevacizumab-induced reversible posterior leukoencephalopathy
      syndrome in patient with rectal cancer.

PMID- 24750202
TI  - Hepatobiliary and pancreatic: leiomyosarcoma of the inferior vena cava.

PMID- 24750203
TI  - Hepatobiliary and pancreatic: bleeding duodenal ulcer associated with coil
      migration after transarterial chemoembolization and radiotherapy.

PMID- 24750204
TI  - Critical incidents among intensive care unit nurses and their need for support:
      explorative interviews.
AB  - AIMS: This article aims (a) to get insight into intensive care nurses' most
      critical work-related incidents, (b) their reactions and coping and (c) perceived
      support, in a Dutch intensive care unit. BACKGROUND: Research about the impact of
      critical incidents has largely been aimed at ambulance and emergency nurses;
      knowledge about intensive care nurses in this respect is scarce. Persistent
      stress reactions after critical incidents may cause symptoms of post-traumatic
      stress disorder, depression and anxiety. Unresolved problems may also cause poor
      behaviour towards patients. In response, nurses reduce work hours or even resign.
      Social support alleviates emotional problems, but little is known about actual
      support perceived. DESIGN: This study is a qualitative explorative study. METHOD:
      Thematic analysis of semi-structured interviews was performed among a purposive
      sample of 12 intensive care nurses in a university hospital in The Netherlands.
      FINDINGS: Four main themes have been identified in critical incidents: high
      emotional involvement in patient-related incidents (in contrast to major life
      threatening events as such), avoidable incidents, sub-standard patient care and
      intimidation. Themes discerned in nurses' reactions after critical incidents were
      physical reactions, emotional reactions and cognitive/behavioural reactions.
      After critical incidents, nurses talked with colleagues, friends or relatives,
      but would have appreciated additional support. CONCLUSIONS: Incidents under
      emotionally demanding circumstances are among the most difficult situations, but
      may not be recognized as critical incidents by colleagues. Both adequate and
      inadequate coping strategies, with long-lasting problems after critical
      incidents, were reported. Feelings of anger, shame and powerlessness, may have
      hindered recovery. Talking to colleagues was perceived to be helpful, but
      intensive care nurses' need for support was insufficiently met. RELEVANCE TO
      CLINICAL PRACTICE: Managers should acknowledge the effects of critical incidents
      on intensive care nurses and take preventive measures: reducing critical
      incidents, improving open communication, imposing a buddy-system for collegial
      support, and timely evaluating the necessity of professional help.

PMID- 24750205
TI  - A functional role for NS5ATP9 in the induction of HCV NS5A-mediated autophagy.
AB  - Autophagy has been shown to facilitate replication of hepatitis C virus (HCV);
      however, the mechanism by which HCV induces autophagy has not been fully
      established. NS5A, a nonstructural protein expressed by HCV, regulates numerous
      cellular pathways, including autophagy, by up-regulating Beclin 1; however, the
      underlying mechanism remains unclear. To obtain new insights into HCV-regulated
      autophagy, NS5ATP9 was overexpressed in HepG2 and L02 cells, resulting in up
      regulation of endogenous Beclin 1 mRNA and protein levels, respectively. The
      luciferase-reporter assay results showed that both NS5A and NS5ATP9 could
      transactivate Beclin 1 promoter activity, but that NS5A could not transactivate
      the Beclin 1 promoter in NS5ATP9-silenced HepG2 and L02 cells. Up-regulation of
      Beclin 1 mRNA and protein expression by NS5A could also be attenuated by NS5ATP9
      knock-down. Furthermore, the HepG2 and L02 cells that transiently overexpressed
      NS5ATP9 had enhanced accumulation of vacuoles carrying the autophagy marker LC3,
      consistent with the conversion of endogenous LC3-I to LC3-II. In contrast, the
      conversion of endogenous LC3-I to LC3-II could not be enhanced by NS5A in NS5ATP9
      silenced HepG2 cells. These results highlight an important potential role for
      NS5ATP9 in HCV NS5A-induced hepatocyte autophagy. 

PMID- 24750206
TI  - Central shunt procedures for complex congenital heart diseases.
AB  - OBJECTIVE: The study was designed to analyze the results of central shunt
      procedure using Gore-Tex grafts for treatment of patients with complex congenital
      heart diseases. METHODS: A Gore-Tex graft was implanted using an end-to-side
      anastomosis technique connecting the aorta with the pulmonary artery. The graft
      size was determined based on the patients' body weight. Artery growth and
      percutaneous plasma oxygen were examined pre- and postoperatively. RESULTS: The
      procedure was performed without cardiopulmonary bypass in 96 of 110 cases. Shunt
      sizes from 3.5 to 6.0 mm were employed. After operation, the oxygen saturations
      increased significantly from 65.2% +/- 7.3 to 84.1% +/- 3.8 (p < 0.05). Both left
      and right pulmonary arteries were found to grow significantly in size, from 4.9
      +/- 1.8 to 7.5 +/- 2.0 mm and from 6.1 +/- 2.3 to 8.0 +/- 4.7 mm, respectively (p
      < 0.05). Early mortality was 5.5% (6/110). Major shunt-related complications
      included congestive heart failure (1.8%, 2/110) and acute shunt occlusion (1.8%,
      2/110). Median follow-up was 18 months (range 6 to 61), with late mortality of
      3.8% (4/104) one month postoperation. CONCLUSION: The central shunt increases
      oxygen saturation and improves pulmonary artery development effectively with a
      relatively low incidence of congestive heart failure, acute occlusion, and
      pulmonary distortion. The adequate postoperation survival, low morbidity and
      mortality, and less technical difficulty of this procedure make it a more
      desirable treatment for complex heart diseases.

PMID- 24750207
TI  - Electrocardiogram patterns during hemodynamic instability in patients with acute
      pulmonary embolism.
AB  - BACKGROUND: We have previously described new electrocardiogram (ECG) findings for
      massive pulmonary embolism, namely ST-segment elevation in lead aVR with ST
      segment depression in leads I and V4 -V6 . However, the ECG patterns of patients
      with acute pulmonary embolism during hemodynamic instability are not fully
      described. METHODS: We compared the differences between the ECG at baseline and
      after deterioration during hemodynamic instability in twenty patients with acute
      pulmonary embolism. RESULTS: Compared with the ECG at baseline, three ischemic
      ECG patterns were found during clinical deterioration with hemodynamic
      instability: ST-segment elevation in lead aVR with concomitant ST-segment
      depression in leads I and V4 -V6 , ST-segment elevation in leads V1 -V3 /V4 , and
      ST-segment elevation in leads III and/or V1 /V2 with concomitant ST-segment
      depression in leads V4 /V5 -V6 . Ischemic ECG patterns with concomitant S1Q3
      and/or abnormal QRS morphology in lead V1 were more common (90%) during
      hemodynamic instability than at baseline (5%) (P = 0.001). CONCLUSIONS:
      Hemodynamic instability in acute pulmonary embolism is reflected by signs of
      myocardial ischemia combined with the right ventricular strain pattern in the 12
      lead ECG.

PMID- 24750208
TI  - Intractable vascular autonomic dysregulation (Harlequin phenomenon) in two
      brothers: another indication for propranolol?
AB  - Vascular autonomic dysregulation, in the most extreme presentation known as
      Harlequin phenomenon, is a rare condition. It manifests as a sudden and brief
      paroxystic change in skin color, resulting in two different colors on the body.
      It is supposed that this condition occurs due to a vasomotor instability. This
      again is caused by sympathetic disautonomy, which is a consequence of
      hypothalamic peripheral vascular tone control immaturity in the newborn.
      Typically, there is spontaneous regression. We describe two brothers who both had
      this condition in their first life years. Clinical symptoms included frequent
      attacks of discoloration of extremities (up to four times per day) accompanied
      with terrifying crying fits, interpreted by the parents as pain. These patients
      were treated with propranolol, a nonselective beta-blocker, resulting in
      improvement of symptoms: only occasional attacks were seen. Beta-blockers act on
      beta1 -adrenoceptors in the heart, thereby preventing the positive chronotropic
      and inotropic effects mediated by these receptors. We hypothesize that
      propranolol, which is very lipophilic and therefore also acts on beta-receptors
      of the central nervous system, acts on the sympathetic system. 

PMID- 24750209
TI  - Increased expression of CXCR3 axis components and matrix metalloproteinase in
      pediatric inflammatory bowel disease patients.
AB  - BACKGROUND: Although pediatric inflammatory bowel disease (IBD) is characterized
      by extensive intestinal involvement and rapid early progression, the precise
      cause and specific factors involved in disease aggravation have not been well
      established. The aim of this study was to investigate the pathogenesis of
      pediatric IBD. METHODS: The expression of inflammatory molecules in colon samples
      taken from active ulcerative colitis (UC) and Crohn's disease (CD) patients was
      compared with those of controls. Three children each with UC and CD in both the
      active and remission phase and their controls were enrolled, and the inflammatory
      gene expression in the mucosa was examined by microarray. Additionally, six
      children from each group were further enrolled in a real-time reverse
      transcription polymerase chain reaction and an immunohistochemical study to
      examine the expression of CXCL9, 10, 11, CXCR3, matrix metalloproteinase (MMP)-1,
      -3, -7, and -10. RESULTS: The microarray analysis revealed enhanced expression of
      the CXCL9, 10, and 11 genes in the active phase of CD. The expression of MMP-1, 
      3, -7, and -10 was significantly enhanced in the active phase of UC. These
      changes were also confirmed by real-time reverse transcription polymerase chain
      reaction. Immunohistochemical analysis revealed enhanced expression of CXCL9, 10,
      and 11 in both the lamina propria and epithelial cells in these patients. CXCR3
      positive cells were also confirmed in the lamina propria. The expression of MMP
      1, -3, -7, and -10 was also enhanced in the mucosal epithelial cells and the
      lamina propria in both CD and UC patients. CONCLUSIONS: These findings suggest
      that CXCR3 axis components and MMP play an important role in the mucosal damage
      in pediatric IBD.

PMID- 24750210
TI  - Relationship between insulin sensitivity and bone mineral density in primary
      hyperparathyroidism.
AB  - INTRODUCTION: Evidence of crosstalk between bone and insulin metabolism has been
      identified. In primary hyperparathyroidism (PHPT), scant data exist on this
      relationship. AIM: To evaluate the relationship between insulin levels or
      sensitivity and bone mineral density (BMD) in PHPT. SUBJECT AND METHODS: Two
      hundred and sixty-seven patients with PHPT without known diabetes mellitus were
      studied. Fasting blood glucose and insulin levels as well as BMD at lumbar spine,
      femoral neck and forearm were measured. Insulin sensitivity was assessed using
      Quantitative Insulin Sensitivity Check Index (QUICKI). The same parameters were
      measured 2 years (interquartile range 2.8 years) after surgery (PTX) in a
      subgroup of patients (n = 51). RESULTS: In univariate analysis, a positive
      relationship between insulin levels and BMD (R = 0.17, P < 0.03) or T-score (R =
      0.20, P < 0.005) was found at femoral neck level. Consequently, a negative
      relationship between QUICKI and femoral BMD (R = -0.20, P < 0.01) or T-score (R =
      -0.21, P < 0.004) was found. In multivariate analysis, when femoral BMD was the
      dependent variable, age (beta = -0.35, P < 0.000004), BMI (beta = 0.39, P <
      0.00001), PTH (beta = -0.18, P < 0.05) and QUICKI (R = -0.15, P < 0.05) had an
      independent effect (R(2) = 0.29). Insulin levels and QUICKI did not change after
      PTX. No relationship was found between QUICKI or insulin levels at the time of
      diagnosis and change in BMD at any site at follow-up. CONCLUSIONS: Our data show
      a weak relationship between insulin levels and/or insulin sensitivity and BMD in
      PHPT. However, the insulin state does not influence change in bone density after
      PTX in PHPT.

PMID- 24750212
TI  - Fine-needle aspiration cytology samples: a good source of material for evaluating
      biomarkers in breast cancer.

PMID- 24750213
TI  - Detailed drawing of a dislocated intraocular lens visualised by a patient.

PMID- 24750211
TI  - Gene expression signatures in motor neurone disease fibroblasts reveal
      dysregulation of metabolism, hypoxia-response and RNA processing functions.
AB  - AIMS: Amyotrophic lateral sclerosis (ALS) and primary lateral sclerosis (PLS) are
      two syndromic variants within the motor neurone disease spectrum. As PLS and most
      ALS cases are sporadic (SALS), this limits the availability of cellular models
      for investigating pathogenic mechanisms and therapeutic targets. The aim of this
      study was to use gene expression profiling to evaluate fibroblasts as cellular
      models for SALS and PLS, to establish whether dysregulated biological processes
      recapitulate those seen in the central nervous system and to elucidate pathways
      that distinguish the clinically defined variants of SALS and PLS. METHODS:
      Microarray analysis was performed on fibroblast RNA and differentially expressed
      genes identified. Genes in enriched biological pathways were validated by
      quantitative PCR and functional assays performed to establish the effect of
      altered RNA levels on the cellular processes. RESULTS: Gene expression profiling
      demonstrated that whilst there were many differentially expressed genes in common
      between SALS and PLS fibroblasts, there were many more expressed specifically in
      the SALS fibroblasts, including those involved in RNA processing and the stress
      response. Functional analysis of the fibroblasts confirmed a significant decrease
      in miRNA production and a reduced response to hypoxia in SALS fibroblasts.
      Furthermore, metabolic gene changes seen in SALS, many of which were also evident
      in PLS fibroblasts, resulted in dysfunctional cellular respiration. CONCLUSIONS:
      The data demonstrate that fibroblasts can act as cellular models for ALS and PLS,
      by establishing the transcriptional changes in known pathogenic pathways that
      confer subsequent functional effects and potentially highlight targets for
      therapeutic intervention.

PMID- 24750214
TI  - Psychological state in patients undergoing coronary artery bypass grafting
      surgery or percutaneous coronary intervention and their spouses.
AB  - Percutaneous coronary intervention (PCI) and the coronary artery bypass grafting
      surgery (CABG) are well accepted treatments for coronary artery disease. Many
      patients and their spouses experience increased level of stress, anxiety and
      depression before and after going under the procedure. One hundred and ninety-six
      cardiac patients who were candidate for CABG or PCI procedures and their spouses
      were asked to complete Hospital Anxiety and Depression Scale and General Health
      Questionnaire-12 before and 1 month after procedures. Anxiety, depression and
      stress level in patients and their spouses going under the procedures
      significantly reduced over time. Scores of anxiety, depression and stress in
      patients and their spouses were correlated. There was no difference in the level
      of anxiety, depression and stress between CABG and PCI groups before to after
      procedures. We suggest providing information about the procedures to both
      patients and their spouses to deal better with their own psychological state. 

PMID- 24750215
TI  - An ORF1-rearranged hepatitis E virus derived from a chronically infected patient
      efficiently replicates in cell culture.
AB  - Hepatitis E is an increasingly reported disease in industrialized countries.
      Studies on the replication cycle of hepatitis E virus (HEV) are hampered due to
      the lack of efficient and robust cell culture systems for this virus. We describe
      the successful isolation of HEV derived from a chronically infected kidney
      transplant patient held under immunosuppressive therapy. Inoculation of serum
      sample 47832 onto the human lung carcinoma cell line A549 resulted in the
      replication of the virus as shown by RT-qPCR. This novel human-derived HEV strain
      is closely related to a wild boar-derived genotype 3 strain, which did not
      replicate in A549 cells. It carries a 186 nucleotide insertion in the
      hypervariable ORF1-region, derived from two parts of its ORF1. By passaging of
      the infected cells, a cell line continuously producing HEV particles was
      generated as demonstrated by RT-qPCR, immuno-electron microscopy, density
      gradient centrifugation and immunohistochemistry. Replication of the produced
      virus was demonstrated after its inoculation onto fresh A549 cells and two
      consecutive passages, whereas heating at 65  degrees C for 2 min abolished its
      infectivity. Several point mutations scattered along the whole genome were
      present in the HEV strain from the second passage; however, the ORF1 insertion
      was still present. Previously, cell culture isolation of two other HEV strains
      carrying insertions in their hypervariable regions, but originating from human
      ribosomal protein genes, has been described. The findings may indicate that cell
      culture adaptation of is mostly dependent on the length and position of the
      insertion, rather than from the sequence itself.

PMID- 24750216
TI  - Dual DNA binding and coactivator functions of Aspergillus nidulans TamA, a
      Zn(II)2Cys6 transcription factor.
AB  - Transcription factors containing DNA binding domains generally regulate
      transcription by direct interaction with DNA. For most transcription factors,
      including the fungal Zn(II)2Cys6 zinc binuclear cluster transcription factors,
      the DNA binding motif is essential for function. However, Aspergillus nidulans
      TamA and the related Saccharomyces cerevisiae Dal81p protein contain Zn(II)2Cys6
      motifs shown to be dispensable for function. TamA acts at several promoters as a
      coactivator of the global nitrogen GATA transcription factor AreA. We now show
      that TamA is the major transcriptional activator of gdhA, encoding the key
      nitrogen metabolism enzyme NADP-glutamate dehydrogenase. Moreover, activation of
      gdhA by TamA occurs primarily by a mechanism requiring the TamA DNA binding
      motif. We show that the TamA DNA binding motif is required for DNA binding of
      FLAG-epitope-tagged TamA to the gdhA promoter. We identify a conserved promoter
      element required for TamA activation, and show that TamA and AreA are
      reciprocally required for full binding at the gdhA promoter under conditions
      where AreA is inactive at most promoters but active at gdhA. Therefore TamA has
      dual functions as a DNA-binding transcription factor and a non-DNA-binding
      coactivator. Dual DNA-binding and coactivator functions provide an additional
      level of combinatorial control to mediate gene-specific expression.

PMID- 24750217
TI  - Serum proteome of nonalcoholic fatty liver disease: a multimodal approach to
      discovery of biomarkers of nonalcoholic steatohepatitis.
AB  - BACKGROUND AND AIM: Nonalcoholic fatty liver disease (NAFLD) is a common
      condition affecting up to 25% of the developed world. It is a progressive
      disease, leading in some to the development of liver cirrhosis. Currently,
      accurate diagnosis and staging of this condition is only possible with
      histological examination of a liver biopsy. This gold standard test is neither
      suitable nor practical for large-scale use as is necessary for a condition as
      common as NAFLD. The aim of this study is to describe the proteome of human NAFLD
      using two distinct shotgun proteomic methods, translating the findings into
      potential biomarkers of NAFLD. METHODS: Two distinct shotgun proteomic techniques
      (iTRAQ and label free) were used to describe the proteome of NAFLD. Thereafter,
      candidate biomarkers were selected for validation by ELISA. RESULTS: Over 550
      protein identifications were made in the description of the NAFLD proteome.
      Several proteins were found to be significantly up/downregulated in nonalcoholic
      steatohepatitis compared with control, including apolipoprotein E (fold ratio of
      1.67), insulin-like growth factor-binding protein 3 (IGFBP3, fold ratio of
      1.642), Vitamin D-binding protein (fold ratio of 4.587), and lymphocyte cytosolic
      protein1 (LCP1, fold ratio of 4.356). ELISA validation of a subset of these
      proteins confirms the validity of the proteomic studies and suggests possible new
      biomarkers of NAFLD. CONCLUSION: Serum markers are able to distinguish between
      the stages of disease in NAFLD as well as detect the grade of fibrosis.
      Ultimately, noninvasive serum markers may replace liver biopsy in the
      investigation of patients with suspected NAFLD.

PMID- 24750218
TI  - Fifteen-year experience and outcomes of pericardiectomy for constrictive
      pericarditis.
AB  - BACKGROUND AND AIM: Constrictive pericarditis has multiple etiologies and can
      lead to disabling symptoms and severe heart failure with poor quality of life.
      Surgical pericardiectomy is the cornerstone of management. All patients
      undergoing pericardiectomy at our institution were reviewed with the goal of
      analyzing preoperative and intraoperative factors that may be associated with
      long-term outcomes. METHODS: A retrospective review of our cardiac surgery
      database identified all patients who underwent pericardiectomy for constrictive
      pericarditis between 1997 and 2012. Demographic, comorbidity, operative, and
      outcome data were analyzed. RESULTS: Thirty-six patients underwent
      pericardiectomy for constrictive pericarditis over 15 years. Etiologies included
      idiopathic (n = 20, 55.6%), postoperative (n = 11, 30.5%), postradiation (n = 3,
      8.3%), and tuberculosis (n = 2, 5.6%). Total pericardiectomy was performed in 35
      patients. The average preoperative cardiac index was 2.6 L/min/m(2) with a
      significant increase to 3.1 L/min/m(2) noted in the immediate postoperative
      period (p = 0.03). There were no perioperative mortalities. The 1-year, 5-year,
      10-year, and 15-year survival rates were 97.2%, 94.6%, 86.5%, and 78.3%,
      respectively. On multivariate analysis, preoperative heart failure (hazard ratio
      2.2, p = 0.06), elevated preoperative total bilirubin (>2.7 mg/dL, hazard ratio
      6.8, p = 0.02), and elevated creatinine (>1.4 mg/dL, hazard ratio 3.1, p = 0.05)
      were risk factors for increased long-term mortality. Kaplan-Meier survival
      analysis showed a significant decrease in overall survival associated with
      postradiation etiology (p = 0.05). CONCLUSIONS: Pericardiectomy can be performed
      with low mortality and immediate improvement in hemodynamics. Those patients with
      compromised cardiac output, abnormal hepatic or renal function, or with previous
      radiation therapy have reduced long-term survival.

PMID- 24750219
TI  - Capture efficiency of cooking-related fine and ultrafine particles by residential
      exhaust hoods.
AB  - Effective exhaust hoods can mitigate the indoor air quality impacts of pollutant
      emissions from residential cooking. This study reports capture efficiencies (CE)
      measured for cooking-generated particles for scripted cooking procedures in a 121
      m3 chamber with kitchenette. CEs also were measured for burner produced CO2
      during cooking and separately for pots and pans containing water. The study used
      four exhaust hoods previously tested by Delp and Singer (Environ. Sci. Technol.,
      2012, 46, 6167-6173). For pan-frying a hamburger over medium heat on the back
      burner, CEs for particles were similar to those for burner produced CO2 and
      mostly above 80%. For stir-frying green beans in a wok (high heat, front burner),
      CEs for burner CO2 during cooking varied by hood and airflow: CEs were 34-38% for
      low (51-68 l/s) and 54-72% for high (109-138 l/s) settings. CEs for 0.3-2.0 MUm
      particles during front burner stir-frying were 3-11% on low and 16-70% on high
      settings. Results indicate that CEs measured for burner CO2 are not predictive of
      CEs of cooking-generated particles under all conditions, but they may be suitable
      to identify devices with CEs above 80% both for burner combustion products and
      for cooking-related particles.

PMID- 24750220
TI  - A need to clarify the outcome of dental education in terms of competence.

PMID- 24750221
TI  - Letter to the editor re.: "Failing to fail...".

PMID- 24750223
TI  - How is research publishing going to progress in the next 20 years? Transcription
      of session for editors, associate editors, publishers and others with an interest
      in scientific publishing held at IADR meeting in Seattle on Wednesday, 20 March
      2013.
AB  - On March 20th 2013, a one-hour session for Editors, Associate Editors, Publishers
      and others with an interest in scientific publishing was held at the IADR
      International Session in Seattle. Organised by Kenneth Eaton and Chris Lynch
      (Chair and Secretary, respectively, of the British Dental Editors Forum), the
      meeting sought to bring together leading international experts in dental
      publishing, as well as authors, reviewers and students engaged in research. The
      meeting was an overwhelming success, with more than 100 attendees. A panel
      involving four leading dental editors led a discussion on anticipated
      developments in publishing dental research with much involvement and contribution
      from audience members. This was the third such meeting held at the IADR for
      Editors, Associate Editors, Publishers and others with an interest in scientific
      publishing. A follow up session will take place in Cape Town on 25 June 2014 as
      part of the annual IADR meeting. The transcript of the meeting is reproduced in
      this article. Where possible speakers are identified by name. At the first time
      of mention their role/ position is also stated, thereafter only their name
      appears. We are grateful to Stephen Hancocks Ltd for their generous sponsorship
      of this event. For those who were not able to attend the authors hope this
      article gives a flavour of the discussions and will encourage colleagues to
      attend future events. Involvement is open to Editors, Associate Editors,
      Publishers and others with an interest in scientific publishing. It is a very
      open group and all those with an interest will be welcome to join in. 

PMID- 24750224
TI  - Intensive care unit nurses' evaluation of simulation used for team training.
AB  - AIM: To implement a simulation-based team training programme and to investigate
      intensive care nurses' evaluations of simulation used for team training.
      BACKGROUND: Simulation-based training is recommended to make health care
      professionals aware of and understand the importance of teamwork related to
      patient safety. DESIGN: The study was based on a questionnaire evaluation design.
      METHODS: A total of 63 registered nurses were recruited: 53 from seven intensive
      care units in four hospitals in one hospital trust and 10 from an intensive care
      postgraduate education programme. After conducting a simulation-based team
      training programme with two scenarios related to emergency situations in the
      intensive care, the participants evaluated each simulation activity with regard
      to: (i) outcome of satisfaction and self-confidence in learning, (ii)
      implementation of educational practice and (iii) simulation design/development.
      RESULT: Intensive care nurses were highly satisfied with their simulation-based
      learning, and they were mostly in agreement with the statements about self
      confidence in learning. They were generally positive in their evaluation of the
      implementation of the educational practice and the simulation design/development.
      Significant differences were found with regard to scenario roles, prior
      simulation experience and area of intensive care practice. CONCLUSION: The study
      indicates a positive reception of a simulation-based programme with regard to
      team training in emergency situations in an intensive care unit. RELEVANCE TO
      CLINICAL PRACTICE: The findings may motivate and facilitate the use of simulation
      for team training to promote patient safety in intensive care and provide
      educators with support to develop and improve simulation-based training
      programmes.

PMID- 24750225
TI  - The natural history of multifocal atrial rhythms in elderly outpatients: insights
      from the "Ikaria study".
AB  - BACKGROUND: Multifocal atrial tachycardias confer an adverse prognosis in
      hospitalized patients. We assessed the prognostic impact of multifocal atrial
      rhythms (MARs-either chaotic atrial rhythm or multifocal atrial
      tachycardia/bradycardia) in very elderly outpatients. METHODS: One hundred ten
      subjects aged 60-74 years, 112 aged 75-89 years, and 61 over 90 years old, were
      enrolled and prospectively evaluated. Several demographic and clinical
      characteristic were recorded in all individuals. RESULTS: A high prevalence of
      MARs was detected in the study population (namely, 6%), which in subjects >90
      years was even higher (15%). Individuals with MARs were older, more often female
      and less active. In multivariate analysis, independent predictors of MARs were
      age (OR = 1.07, 95% CI: 1.02-1.13, P = 0.01) and female sex (OR = 4.77, 95% CI:
      1.23-18.48, P = 0.02). The mortality rate during the follow-up period was 8.4%
      without differences between age groups (P = 0.209). In particular, mortality rate
      was 6% in individuals with MARs and 9% in those without (P = 0.72). Mortality was
      associated with age (OR 1.07, 95% CI: 1.02-1.12, P = 0.005) and history of
      cardiovascular disease at baseline (OR 4.57, 95% CI: 1.87-11.2 P = 0.001).
      CONCLUSIONS: Contrary to hospitalized individuals with multifocal atrial
      tachycardias, MARs were not associated with increased mortality in elderly
      outpatients in this study.

PMID- 24750226
TI  - Comparison of the blood supply to the articular-epiphyseal growth complex in
      horse vs. pony foals.
AB  - REASONS FOR PERFORMING STUDY: To increase understanding of why the prevalence of
      clinical/radiographic osteochondrosis (OC) dissecans is high in horses and low in
      ponies. OBJECTIVES: To investigate whether the clinical difference in OC
      occurrence between horses and ponies could partly be explained by a difference
      in: 1) number of patent vessels in the epiphyseal growth cartilage; 2) duration
      of the presence of patent cartilage canals; or 3) growth cartilage thickness at
      predilection sites for OC. The hypothesis was that pony foals would have fewer
      cartilage canals, shorter duration of blood supply and thinner growth cartilage
      than horse foals. STUDY DESIGN: Observational, cross-sectional study. METHODS:
      Nine Standardbred foals (horse group) 1-49 days old and 11 Norwegian Fjord foals
      (pony group) 1-62 days old were included. A total of 15 anatomical locations in
      the tarsocrural and metatarsophalangeal joints were examined by one or more of
      the following techniques: arterial perfusion; photography of cleared specimens;
      microcomputed tomography; radiography; and histology. The number of cartilage
      canals was counted. Cartilage thickness was measured. Duration of blood supply
      was assessed in histological sections. RESULTS: Of the 3 common predilection
      sites for OC investigated, there were significantly fewer vessels (P = 0.003) and
      thinner cartilage (P = 0.002) at the distal lateral trochlear ridge of the talus
      in the pony group. There was no difference in the duration of presence of
      cartilage canals between the groups. CONCLUSION: The hypothesis that pony foals
      would have fewer cartilage canals and thinner growth cartilage than horse foals
      was confirmed for the lateral trochlear ridge of the talus. The current results
      may contribute towards an explanation for the low prevalence of OC at the distal
      lateral trochlear ridge of the talus in pony foals.

PMID- 24750227
TI  - Occurrence of giant focal forms of congenital hyperinsulinism with incorrect
      visualization by (18) F DOPA-PET/CT scanning.
AB  - CONTEXT: Congenital hyperinsulinism (CHI) is a rare disease characterized by
      severe hypoglycaemic episodes due to pathologically increased insulin secretion
      from the pancreatic beta cells. When untreated, CHI might result in irreversible
      brain damage and death. Currently, two major subtypes of CHI are known: a focal
      form, associated with local distribution of affected beta cells and a nonfocal
      form, affecting every single beta cell. The identification of focal forms is
      important, as the patients can be cured by limited surgery. (18) F DOPA-PET/CT is
      an established non-invasive approach to differentiate focal from nonfocal CHI.
      OBJECTIVE: The purpose of this study was to identify possible limitations of (18)
      F DOPA-PET/CT scan in patients with focal forms nonfocal CHI. DESIGN: A
      retrospective chart review of 32 patients (from 2008 through 2013) who underwent
      (18) F DOPA-PET/CT and partial pancreatectomy for focal CHI at the reference
      centres in Berlin, Germany and London, UK. RESULTS: In most cases (n = 29,
      90.7%), (18) F DOPA-PET/CT was sufficient to localize the complete focal lesion.
      However, in some patients (n = 3, 9.3%), (18) F DOPA-PET/CT wrongly visualized
      only a small portion of the focal lesion. In this group of patients, a so-called
      'giant focus' was detected in histopathological analysis during the surgery.
      CONCLUSIONS: Our data show that in most patients with focal CHI (18) F DOPA
      PET/CT correctly predicts the size and anatomical localisation of the lesion.
      However, in those patients with a 'giant focal' lesion (18) F DOPA-PET/CT is
      unreliable for correct identification of 'giant focus' cases.

PMID- 24750228
TI  - Cinematic magnetic resonance enterography for non-organic abdominal pain in
      infants and children.
AB  - BACKGROUND: Recurrent non-organic abdominal pain is the most commonly diagnosed
      medical problem in children. However, excluding small bowel disease remains a
      challenge. We evaluated our exclusion criteria for organic small intestinal
      diseases in pediatric patients with recurrent non-organic abdominal pain using
      cinematic magnetic resonance (cine-MR) enterography. METHODS: The non-intestinal
      organic (non-IO) group as classified by the Rome III criteria system and the
      intestinal organic (IO) group consisted of 81 and 19 patients, with 35 and 12
      male and 46 and 7 female patients with an age range of 5-18 and 4-15 years
      (average 10.5 and 10.5 years), respectively. Cine-MR enterography was performed
      by dynamically balanced first-field-echo imaging with thick-slice water-selective
      excitation without breath holding. In our original small intestinal motility
      test, cine-MR enterography was taken at three different times (fasting state
      [P1], immediately after [P2] and 30 min after [P3] drinking liquid material),
      with images taken sequentially for 5 min at each time-point to evaluate the
      motion of water in the gastrointestinal tract. Positive findings for organic
      intestinal problems were concluded when persistent visible intestinal loops
      appeared in both the P1 and P2 phases. RESULTS: Cine-MR enterography showed 6/81
      (7.4%) and 18/19 (94.7%) (P < 0.01) positive cases of organic intestinal problems
      in the non-IO and IO groups, respectively. Positive and negative predictive
      values of this examination were 78.3% and 97.4%, respectively. CONCLUSIONS: The
      unique capabilities of cine-MR enterography technology in this clinical setting
      render it an important additional diagnostic tool when specific disease
      management issues must be addressed.

PMID- 24750229
TI  - Loss of nuclear TDP-43 in amyotrophic lateral sclerosis (ALS) causes altered
      expression of splicing machinery and widespread dysregulation of RNA splicing in
      motor neurones.
AB  - AIMS: Loss of nuclear TDP-43 characterizes sporadic and most familial forms of
      amyotrophic lateral sclerosis (ALS). TDP-43 (encoded by TARDBP) has multiple
      roles in RNA processing. We aimed to determine whether (1) RNA splicing
      dysregulation is present in lower motor neurones in ALS and in a motor neurone
      like cell model; and (2) TARDBP mutations (mtTARDBP) are associated with aberrant
      RNA splicing using patient-derived fibroblasts. METHODS: Affymetrix exon arrays
      were used to study mRNA expression and splicing in lower motor neurones obtained
      by laser capture microdissection of autopsy tissue from individuals with sporadic
      ALS and TDP-43 proteinopathy. Findings were confirmed by quantitative reverse
      transcription-polymerase chain reaction (qRT-PCR) and in NSC34 motor neuronal
      cells following shRNA-mediated TDP-43 depletion. Exon arrays and
      immunohistochemistry were used to study mRNA splicing and TDP-43 expression in
      fibroblasts from patients with mtTARDBP-associated, sporadic and mutant SOD1
      associated ALS. RESULTS: We found altered expression of spliceosome components in
      motor neurones and widespread aberrations of mRNA splicing that specifically
      affected genes involved in ribonucleotide binding. This was confirmed in TDP-43
      depleted NSC34 cells. Fibroblasts with mtTARDBP showed loss of nuclear TDP-43
      protein and demonstrated similar changes in splicing and gene expression, which
      were not present in fibroblasts from patients with sporadic or SOD1-related ALS.
      CONCLUSION: Loss of nuclear TDP-43 is associated with RNA processing
      abnormalities in ALS motor neurones, patient-derived cells with mtTARDBP, and
      following artificial TDP-43 depletion, suggesting that splicing dysregulation
      directly contributes to disease pathogenesis. Key functional pathways affected
      include those central to RNA metabolism.

PMID- 24750230
TI  - Pathological evaluation of the staging axillary lymph nodes for breast cancer: a
      national survey in the United Kingdom.
AB  - AIMS: The handling and examination of sentinel lymph nodes (SLNs) to detect
      metastasis is critical in the assessment of early breast cancer patients. This
      survey investigates the variation in practise followed by pathology units across
      the United Kingdom in the staging evaluation of axillary lymph nodes (ALNs).
      METHODS AND RESULTS: A structured questionnaire, approved by the National Health
      Service Breast Screening Programme pathology Big 18 committee, was circulated
      among all pathologists. There were 160 respondents; 92% performed SLN biopsy for
      staging, 97% had a protocol for processing SLNs and most laboratories examined
      the ALNs using formalin-fixed, paraffin-embedded (FFPE) samples (85.6%). A few
      used PCR (7.5%), frozen section (3.8%) or touch imprint cytology (3.1%), with or
      without subsequent FFPE section examination. Currently, 33% perform serial
      sectioning, with the majority of the rest (75%) staining three levels using H&E.
      Most units (85%) undertook immunohistochemistry evaluation only when suspicious
      cells were detected on H&E-stained sections. CONCLUSIONS: The range of practise
      in UK histopathology departments is described with regard to the dissection and
      evaluation of ALNs/SLN biopsy. The variation in practise was not very marked and
      most departments adhered to national guidelines. Any UK study seeking to relate
      ALN status and outcome would need to be mindful of the variability in nodal
      processing and examination.

PMID- 24750231
TI  - Intraoperative rapid diagnosis of primary central nervous system lymphomas:
      advantages and pitfalls.
AB  - To study the advantages and pitfalls of intraoperative rapid diagnosis (IRD) of
      primary central nervous system lymphomas (PCNSL), pathology reports and frozen
      sections in our institution were reviewed. We examined 27 cases of PCNSL, one
      case of anaplastic glioma, and one case of metastatic brain tumor that were
      diagnosed on neuroimaging. Fifteen cases of intraoperative cytological
      preparations were also reviewed in a correlative manner. Among the 27 cases
      initially diagnosed as PCNSL, 18 were also diagnosed as PCNSL by IRD. However,
      IRD identified four of the 27 cases as gliosis, two as demyelination, one as
      atypical epithelial cells, one as malignant glioma and anaplastic astrocytoma. In
      addition, the case identified as metastatic brain tumor on neuroimaging was
      corrected to a diagnosis of PCNSL based on IRD. The final accuracy of IRD in the
      present study was 89.6% (26/29). After postoperative definitive diagnosis, two
      cases of anaplastic astrocytoma and one case of PCNSL by IRD were corrected to
      PCNSL, anaplastic oligodendroglioma and demyelination, respectively. PCNSL were
      sometimes histologically indistinguishable from malignant gliomas or
      demyelinating diseases in the present study, particularly in frozen sections.
      Notably, all cases for which both intraoperative cytology and frozen section were
      performed concomitantly were correctly diagnosed in the present study. In
      particular, lymphoglandular bodies were highly characteristic cytological
      findings of PCNSL. Both intraoperative cytology and frozen sections should
      therefore be performed concomitantly when PCNSL are suspected. 

PMID- 24750233
TI  - Prognostic value of systemic inflammation-based markers in advanced pancreatic
      cancer.
AB  - BACKGROUND: The prognostic significance of various systemic inflammation-based
      markers has been explored in different cancers. These markers can be used to
      assist with decision-making in oncology clinics. AIM: The aim of this study was
      to investigate the prognostic significance of three systemic inflammation-based
      factors: neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR) and
      modified Glasgow Prognostic Score (mGPS) in patients with advanced pancreatic
      cancer. METHODS: Data were collected retrospectively for advanced pancreatic
      cancer patients treated between 1 January 2008 and 31 December 2012 at the Royal
      Perth Hospital. The ratios were dichotomised as <5 versus >=5 for NLR and <200
      versus >=200 for PLR. Modified Glasgow Prognostic Scores were scored as: mGPS '0'
      = both C-reactive protein (CRP) and albumin normal, mGPS '1' = elevated CRP < 10
      mg/L and mGPS '2' = both elevated CRP > 10 mg/L and albumin < 35 g/L. Univariate
      and multivariate analyses were carried out. RESULTS: Data were evaluable for 124
      patients. Median survivals based on the three inflammation-based prognostic
      markers evaluated were: NLR <5 versus >=5 = 8.5 months versus 2.6 months
      respectively (P = 0.0007; hazard ratio (HR) 1.81), PLR <200 versus >=200 = 9.1
      months versus 4 months respectively (P = 0.007; HR 1.64) and mGPS score 1, 2, 3 =
      8.3 months, 9.6 months and 1.8 months respectively (P = 0.0004). Besides Eastern
      Cooperative Oncology Group performance status, NLR, PLR and mGPS were significant
      independent prognostic markers both on univariate as well as multivariate
      analysis. CONCLUSIONS: Our findings suggest that the NLR, PLR and mGPS derived
      from routine blood tests can be used as clinically meaningful biomarkers to
      stratify advanced pancreatic cancer patients into different prognostic groups.

PMID- 24750232
TI  - Prize-based contingency management for the treatment of substance abusers: a meta
      analysis.
AB  - AIM: To review randomized controlled trials to assess efficacy of a prize-based
      contingency management procedure in reducing substance use (where a drug-free
      breath or urine sample provides a chance of winning a prize). METHODS: A meta
      analysis was conducted on papers published from January 2000 to February 2013 to
      determine the effect size of studies comparing prize-based contingency management
      to a treatment-as-usual control condition (k = 19 studies). Parallel analyses
      evaluated the efficacy of both short- (k = nine studies) and long-term outcomes
      (k = six studies) of prize-based contingency management. RESULTS: The average end
      of-treatment effect size (Cohen's d) was 0.46 [95% confidence interval (CI) =
      0.37, 0.54]. This effect size decreased at the short-term (<=3-month) post
      intervention follow-up to 0.33 (95% CI = 0.12, 0.54) and at the 6-month follow-up
      time-point there was no detectable effect [d = -0.09 (95% CI = -0.28, 0.10)].
      CONCLUSION: Adding prize-based contingency management to behavioral support for
      substance use disorders can increase short-term abstinence, but the effect does
      not appear to persist to 6 months.

PMID- 24750234
TI  - The study of perceived stress, coping strategy and self-efficacy of Chinese
      undergraduate nursing students in clinical practice.
AB  - The aim of the study was to explore the coping strategy and the effects of self
      efficacy of Chinese undergraduate nursing students when they face the stress in
      clinical practice. Convenience sampling was used to recruit undergraduate nursing
      students in Mainland China who have practiced 3 months in hospitals in their
      final college year. Self-report questionnaires including demographics, Perceived
      Stress Scale, coping behaviour inventory and Generalized Self-Efficacy Scale were
      collected. The results showed that during clinical practice, assignments and
      workload were the most common stress to students; transference was the most
      frequently used coping strategy by students. Self-efficacy not only had a
      positive main effect in predicting the frequency of use of staying optimistic and
      problem solving strategies but also moderated the effects of stress from taking
      care of patients on transference strategy, as well as stress from assignments and
      workload on problem solving strategy. It is essential to bolster the students'
      self-efficacy to reduce stress and adopt positively the coping strategies during
      clinical practice. 

PMID- 24750235
TI  - Human convective boundary layer and its interaction with room ventilation flow.
AB  - This study investigates the interaction between the human convective boundary
      layer (CBL) and uniform airflow with different velocity and from different
      directions. Human body is resembled by a thermal manikin with complex body shape
      and surface temperature distribution as the skin temperature of an average
      person. Particle image velocimetry (PIV) and pseudocolor visualization (PCV) are
      applied to identify the flow around the manikin's body. The findings show that
      the direction and magnitude of the surrounding airflows considerably influence
      the airflow distribution around the human body. Downward flow with velocity of
      0.175 m/s does not influence the convective flow in the breathing zone, while
      flow at 0.30 m/s collides with the CBL at the nose level reducing the peak
      velocity from 0.185 to 0.10 m/s. Transverse horizontal flow disturbs the CBL at
      the breathing zone even at 0.175 m/s. A sitting manikin exposed to airflow from
      below with velocity of 0.30 and 0.425 m/s assisting the CBL reduces the peak
      velocity in the breathing zone and changes the flow pattern around the body,
      compared to the assisting flow of 0.175 m/s or quiescent conditions. In this
      case, the airflow interaction is strongly affected by the presence of the chair. 

PMID- 24750236
TI  - Liver laceration from a diaphragmatic suture in minithoracotomy mitral valve
      repair.
AB  - Mitral valve operations are increasingly performed through minimally invasive
      approaches such as the right anterior minithoracotomy. To facilitate exposure
      with this technique, a diaphragmatic suture may be implemented. We describe a
      liver laceration caused by the diaphragmatic suture in minithoracotomy mitral
      repair and its successful nonoperative management with arterial embolization.

PMID- 24750237
TI  - Bovine pancreatic trypsin inhibitor is a new antifungal peptide that inhibits
      cellular magnesium uptake.
AB  - Antimicrobial peptides (AMPs) are promising agents for control of bacterial and
      fungal infections. Traditionally, AMPs were thought to act through membrane
      disruption but recent experiments have revealed a diversity of mechanisms. Here
      we describe a novel antifungal activity for bovine pancreatic trypsin inhibitor
      (BPTI). BPTI has several features in common with a subset of antimicrobial
      proteins in that it is small, cationic and stabilized by disulphide bonds. BPTI
      inhibits growth of Saccharomyces cerevisiae and the human pathogen Candida
      albicans. Screening of the yeast heterozygous essential deletion collection
      identified the magnesium transporter Alr1p as a potential BPTI target. BPTI
      treatment of wild type cells resulted in a lowering of cellular Mg(2+) levels.
      Populations treated with BPTI had fewer cells in S-phase of the cell cycle and a
      corresponding increase of cells in G(0)/G(1) and G(2) phases. The same patterns
      of cell cycle arrest obtained with BPTI were also obtained with the magnesium
      channel inhibitor hexamine(III)cobalt chloride. Analysis of the growth inhibition
      of C. albicans revealed that BPTI is inhibiting growth via the same mechanism in
      the two yeast species. Inhibition of magnesium uptake by BPTI represents a novel
      mechanism of action for AMPs.

PMID- 24750238
TI  - Relationship of electrocardiographic left ventricular hypertrophy to the presence
      of diastolic dysfunction.
AB  - BACKGROUND: Left ventricular (LV) diastolic dysfunction (DD) is a known predictor
      of poor cardiovascular outcomes. Although ECG LV hypertrophy (LVH) is strongly
      associated with LV systolic dysfunction and heart failure, the relation of LV DD
      to ECG LVH is unclear. METHODS: ECG LVH by Cornell product (CP) criteria was
      examined in a cohort of 185 patients who underwent both cardiac computed
      tomographic angiography and transthoracic echocardiography with complete
      evaluation of diastolic function. The presence of DD was determined via
      evaluation of mitral inflow velocities, tissue Doppler imaging, deceleration
      time, isovolumic relaxation time, pulmonary venous systolic: diastolic ratio, and
      left atrial enlargement. RESULTS: Among the 185 patients (56% female, mean age
      54.6 +/- 15.6), 105 (57%) had DD. In univariate logistic regression analysis,
      patients in the upper quartile of CP (>=1595 mm.ms) had a >5-fold greater odds of
      DD (odds ratio [OR] 5.1, 95% confidence interval [CI] 2.2-11.7, P < 0.001). In
      alternative analyses treating CP as a continuous variable, each 1 SD increase in
      CP (664 mm.ms) was associated with an OR of 1.9 for DD (95% CI 1.3-2.7, P <
      0.001). In multivariate logistic regression analyses adjusting for univariate
      predictors of DD, the highest quartile of CP remained associated with a 5.9-fold
      increased odds of DD (95% CI 2.3-15.4, P = 0.001), and each 1 SD of CP with a 1.7
      fold increased odds of DD (95% CI 1.2-2.5, P = 0.005). CONCLUSIONS: CP LVH is a
      strong predictor of DD, even after adjustment for other potential risk factors
      and ECG variables.

PMID- 24750239
TI  - Ribavirin suppresses erythroid differentiation and proliferation in chronic
      hepatitis C patients.
AB  - Combination therapy with pegylated interferon (pegIFN) plus ribavirin (RBV) is
      the standard of care for chronic hepatitis C. One of the major treatment-related
      side effects is anaemia, attributed to RBV-induced haemolysis. However,
      haemolysis biomarkers are not present in all patients supporting the existence of
      other pathogenetic mechanisms. We studied the role of RBV in inducing haemolysis
      and its effects on erythropoiesis. In 18 hepatitis C virus (HCV) genotype 2
      patients treated with pegIFN-alpha-2a (180 mcg/week) plus RBV (800 mg/day) for 24
      weeks and in 10 hepatitis B virus (HBV) patients treated with pegIFN-alpha-2a
      (180 mcg/week) for 48 weeks, haemolysis was assessed by serum LDH, haptoglobin
      and reticulocyte count. Erythropoiesis was evaluated both ex vivo, analysing the
      clonogenic activity of patients' erythroid progenitors, as well as in vitro
      adding pegIFN and RBV to liquid cultures obtained from CD34+ cells of healthy
      volunteers. The majority of patients developed anaemia; the week 4 mean
      haemoglobin decrease was greater in HCV than in HBV patients (1.7 vs 0.47 g/dL, P
      = 0.01). Only three HCV patients (17%) and no HBV patients showed signs of
      haemolysis. The 15 nonhaemolytic HCV patients and all HBV patients showed a delay
      in erythroid differentiation, with a reduction in colony number and a relative
      increase in undifferentiated colony percentage. Haemolytic HCV patients had an
      increase in colony number at week 4 of therapy. In vitro, erythroid cell
      proliferation and differentiation were inhibited by both pegIFN and RBV. Both
      pegIFN and RBV have an inhibitory effect on erythroid proliferation and
      differentiation.

PMID- 24750240
TI  - Nurses well-being in intensive care units: study of factors promoting team
      commitment.
AB  - BACKGROUND: Intensive care units (ICUs) are challenging work environments because
      of the critical condition of patients, and ICU nurses frequently lament low job
      satisfaction and high staff turnover. Nevertheless, organizational and work
      characteristics, and the quality of relationships with staff can help to maintain
      nurses' enthusiasm and increase job satisfaction. AIM: The aim of this study was
      to analyse how nursing work environment factors affect identification and
      commitment among ICU nurses. DESIGN: A cross-sectional study was carried out in
      12 ICUs from four Italian urban hospitals. METHOD: A total of 222 nurses
      participated and completed a self-reported questionnaire. RESULTS AND CONCLUSION:
      Results show that nursing work characteristics are directly related to team
      commitment, and that the nursing work characteristics and team commitment
      relationship was mediated by both perceived supervisor support and job
      satisfaction. RELEVANCE TO CLINICAL PRACTICE: Our findings may concretely
      contribute to literature and offer additional suggestions to improve nurses' work
      conditions and patient health in ICUs.

PMID- 24750241
TI  - Outcome of infants presenting rectal bleeding: a retrospective study in a single
      institution.
AB  - BACKGROUND: Although rectal bleeding in infancy (RBI) is not a rare phenomenon,
      the clinical course of RBI is not fully understood. METHODS: To investigate the
      outcome and pathogenesis of RBI, especially when concomitant with food-protein
      induced proctocolitis (FPIP) and neonatal transient eosinophilic colitis (NTEC),
      22 neonates with rectal bleeding with FPIP and NTEC from January 2008 to June
      2012 were enrolled and their clinical course and mechanisms of inflammation were
      examined. RESULTS: Thirteen infants showed rectal bleeding after feeding and were
      diagnosed with FPIP, and nine infants showed rectal bleeding before feeding and
      were diagnosed with NTEC. Elevated peripheral white blood cell (12,685 +/-
      3754/MUl and 30,978 +/- 16,166/MUl) and eosinophil (1084 +/- 816/MUl and 4456 +/-
      3341/MUl) were confirmed in FPIP and NTEC, respectively. Colonoscopy revealed
      nodular lymphoid hyperplasia, a pale mucosal surface and oozing with diffuse
      infiltration of neutrophils, lymphocytes, and eosinophils in both groups. Reverse
      transcription polymerase chain reaction analysis revealed enhanced expression of
      the interleukin-6, CCL11, and CXCL13 genes, where CXCL13 expression was more
      prominent in FPIP. Mucosal infiltration by CD3- and immunoglobulin-A- but not
      immunoglobulin-E-positive cells was confirmed. Among them, only one infant with
      FPIP developed milk allergy, whereas none with NTEC had developed milk allergy at
      the age of 1 year. CONCLUSIONS: FPIP in infancy and NTEC are similar diseases and
      interleukin-6, CCL11, and CXCL13 may play a major role in the pathogenesis of
      rectal bleeding. Although the involvement of allergic reaction is possible, milk
      allergy was not a common outcome after 1 year of follow up.

PMID- 24750243
TI  - Using cognitive modelling to investigate the psychological processes of the
      Go/NoGo discrimination task in male abstinent heroin misusers.
AB  - AIMS: To use cognitive modelling to investigate psychological processes
      underlying decision-making in male abstinent heroin misusers (AHMs). DESIGN: A
      case-control study design. SETTING: A drug misuse treatment centre in Taiwan.
      PARTICIPANTS: Eighty-eight male AHMs and 48 male controls. MEASUREMENTS: Four
      parameters representing the attention to wins, learning rate, response
      sensitivity and incentive of heroin-related stimuli from the modified Go/NoGo
      discrimination task. FINDINGS: A modified cue-dependent learning (CD) model with
      four parameters representing attention to wins, learning rate, response
      sensitivity and incentive of heroin-related stimuli had a lower value of the sum
      of Bayesian information criterion (showing a better fit) than the original CD
      model (9555.50 versus 11,192.22, P < 0.001). The AHM group had a higher value of
      the heroin-incentive parameter than the control group (0.26 versus -1.66, P <
      0.05). The attention to wins and heroin-incentive parameters were associated
      positively with total commission rate and negatively with total omission rate in
      the AHM group (P < 0.001). CONCLUSIONS: Male abstinent heroin misusers appear to
      be more influenced by heroin-related stimuli during decision-making than males
      with no history of heroin misuse.

PMID- 24750242
TI  - RAC1 inhibition as a therapeutic target for gefitinib-resistant non-small-cell
      lung cancer.
AB  - Although epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (EGFR
      TKI), including gefitinib, provide a significant clinical benefit in non-small
      cell lung cancer (NSCLC) patients, the acquisition of drug resistance has been
      known to limit the efficacy of EGFR-TKI therapy. In this study, we demonstrated
      the involvement of EGF-EGFR signaling in NSCLC cell migration and the requirement
      of RAC1 in EGFR-mediated progression of NSCLC. We showed the significant role of
      RAC1 pathway in the cell migration or lamellipodia formation by using gene
      silencing of RAC1 or induction of constitutive active RAC1 in EGFR-mutant NSCLC
      cells. Importantly, the RAC1 inhibition suppressed EGFR-mutant NSCLC cell
      migration and growth in vitro, and growth in vivo even in the gefitinib-resistant
      cells. In addition, these suppressions by RAC1 inhibition were mediated through
      MEK or PI3K independent mechanisms. Collectively, these results open up a new
      opportunity to control the cancer progression by targeting the RAC1 pathway to
      overcome the resistance to EGFR-TKI in NSCLC patients. 

PMID- 24750244
TI  - Signet-ring cell change in adenoid cystic carcinoma: a clinicopathologic and
      immunohistochemical study of four cases.
AB  - AIMS:   Signet-ring cell (SRC) change has not been reported in adenoid cystic
      carcinomas (ACC). This study describes the clinicopathological and
      immunohistochemical findings in four cases of ACC with SRCs (ACC-SRC), in which
      the relative proportion of the SRC component ranged from 25% to 50%. METHODS AND
      RESULTS:   The median age was 58 years (range: 48 to 81 y) and all patients were
      women. The involved sites were sinonasal, lip and submandibular. Two patients
      developed lung metastasis and one died of disease 63 months after tumor
      resection. Neither mucinous nor lipid substances were detected in the SRCs. These
      were positive for AE1/AE3, CK14 and EMA; which highlighted the intracytoplasmic
      vacuole borders. The SRC nests were surrounded by alpha-SMA and p63 positive
      myoepithelial cells. When compared to the conventional component, the SRCs
      exhibited similar p53 positivity but lower Ki-67 and mitotic indices. SRCs were C
      Myb negative. Ultrastructural examination revealed that the intracytoplasmic
      vacuoles were lumens lined by microvilli. CONCLUSIONS:   ACC-SRC is a nonmucin
      and nonlipid producing phenomenon, possibly related to disturbed differentiation
      of ductal/luminal cells. This cellular modification in ACC apparently does not
      change the biological behavior of the tumor but it may cause significant
      diagnostic problems, particularly in incisional biopsies. (c) 2012 Blackwell
      Publishing Ltd.

PMID- 24750245
TI  - Re-evaluation of the sepsis score in equine neonates.
AB  - REASONS FOR PERFORMING STUDY: The modified sepsis scoring system provides a
      method to identify sepsis in foals early in the disease process, but inconsistent
      results have been obtained from its clinical application in previous studies.
      OBJECTIVES: To evaluate the sensitivity and specificity of the modified sepsis
      score in a larger population of foals. A secondary objective was to identify
      factors associated with sepsis. STUDY DESIGN: Retrospective cohort study.
      METHODS: Records were retrospectively analysed for neonatal admissions to the
      University of Florida Large Animal Hospital from 1982 to 2008. Backwards stepwise
      multivariable logistic regression was used to evaluate objective clinical factors
      associated with sepsis. Receiver operating chararacteristic ROC curve analysis
      was performed on the modified sepsis score and used to determine an optimal cut
      point. RESULTS: A total of 1065 foals were included in the study. The modified
      sepsis score had a sensitivity of 56.4% and specificity of 73.4% for the
      originally suggested cut point (>11). Receiver operating chararacteristic
      analysis revealed an optimal cut point of >7 (sensitivity 84.4%, specificity
      41.8%). The modified sepsis score performed better than the generated regression
      model which included age, creatinine, lymphocytes, potassium and IgG>8 g/l (P =
      0.026). Diagnostic performance of the modified sepsis score did not change
      significantly over time. CONCLUSIONS: Sensitivity and specificity of the modified
      sepsis score were not as high as previously documented, but the score still
      outperformed a regression model derived from objective clinical data. The Summary
      is available in Chinese - see Supporting information.

PMID- 24750248
TI  - The attitudes of nursing students towards lesbians and gay males in Turkey.
AB  - This study was conducted with 158 nursing students using the Homosexuality
      Attitudes Scale as a descriptive and explorative study to determine the attitudes
      of nursing students towards lesbians and gay males and the affecting factors. As
      a result, it was found that the students' attitudes were moderately homophobic;
      stronger religious belief, conversing with others about homosexuality and the
      idea of making friends with lesbians and gay males positively affected this
      attitude. It is thought that this study will help increase the awareness of
      working nurses and students at the school of nursing towards lesbians and gay
      males. 

PMID- 24750247
TI  - Mitochondrial and inflammatory changes in sporadic inclusion body myositis.
AB  - AIMS: Sporadic inclusion body myositis (sIBM) is the most common late onset
      muscle disease causing progressive weakness. In light of the lack of effective
      treatment, we investigated potential causes underlying muscle wasting. We
      hypothesized that accumulation of mitochondrial respiratory deficiency in muscle
      fibres may lead to fibre atrophy and degeneration, contributing to muscle mass
      reduction. METHODS: Histochemical and immunohistochemical analyses were performed
      on muscle biopsies from 16 sIBM patients to detect activity of mitochondrial
      enzymes and expression of mitochondrial respiratory chain proteins along with
      inflammatory markers respectively. Mitochondrial DNA mutations were assessed in
      single muscle fibres using real-time PCR. RESULTS: We identified respiratory
      deficient fibres at different stages of mitochondrial dysfunction, with
      downregulated expression of complex I of mitochondrial respiratory chain being
      the initial feature. We detected mitochondrial DNA rearrangements in the majority
      of individual respiratory-deficient muscle fibres. There was a strong correlation
      between number of T lymphocytes and macrophages residing in muscle tissue and the
      abundance of respiratory-deficient fibres. Moreover, we found that respiratory
      deficient muscle fibres were more likely to be atrophic compared with respiratory
      normal counterparts. CONCLUSIONS: Our findings suggest that mitochondrial
      dysfunction has a role in sIBM progression. A strong correlation between the
      severity of inflammation, degree of mitochondrial changes and atrophy implicated
      existence of a mechanistic link between these three parameters. We propose a role
      for inflammatory cells in the initiation of mitochondrial DNA damage, which when
      accumulated, causes respiratory dysfunction, fibre atrophy and ultimately
      degeneration of muscle fibres.

PMID- 24750249
TI  - Current concepts in the diagnosis and management of type 1 gastric neuroendocrine
      neoplasms.
AB  - The vast majority of gastrin-related gastrointestinal neuroendocrine neoplasms
      (GI-NENs) develop in the context of chronic atrophic gastritis (type 1), a
      condition closely related to autoimmune thyroid diseases. These neoplasms are
      defined as gastric NENs type 1 (GNEN1) and have recently been shown to constitute
      the commonest GI-NENs in a prospective study. GNEN1s are usually multiple and
      follow a relative indolent course, raising questions regarding the extent that
      such patients should be investigated and the appropriate therapeutic
      interventions needed. Recently, a number of consensus statements and guidelines
      have been published from various societies dealing with the diagnosis and
      management of GI-NENs. Endocrinologists are among the many different medical
      specialties involved in GNEN1s diagnosis and management. However, despite recent
      advances, few randomized trials are available, and thus existing evidence remains
      relatively weak compared to other malignancies. The purpose of this review is to
      provide recent evidence along with currently employed modalities addressing the
      diagnosis, management, long-term follow-up and potential comorbidities of GNEN1s.

PMID- 24750250
TI  - The phosphotransferase system gene ptsI in the endophytic bacterium Bacillus
      cereus is required for biofilm formation, colonization, and biocontrol against
      wheat sharp eyespot.
AB  - Natural resistance of wheat plants to wheat sharp eyespot is inadequate, and new
      strategies for controlling the disease are required. Biological control is an
      alternative and attractive way of reducing the use of chemicals in agriculture.
      In this study, we investigated the biocontrol properties of endophytic bacterium
      Bacillus cereus strain 0-9, which was isolated from the root systems of healthy
      wheat varieties. The phosphotransferase system is a major regulator of
      carbohydrate metabolism in bacteria. Enzyme I is one of the protein components of
      this system. Specific disruption and complementation of the enzyme I-coding gene
      ptsI from B. cereus was achieved through homologous recombination. Disruption of
      ptsI in B. cereus caused a 70% reduction in biofilm formation, a 30.4% decrease
      in biocontrol efficacy, and a 1000-fold reduction in colonization. The growth of
      DeltaptsI mutant strain on G-tris synthetic medium containing glucose as the
      exclusive carbon source was also reduced. Wild-type properties could be restored
      to the DeltaptsI mutant strain by ptsI complementation. These results suggested
      that ptsI may be one of the key genes involved in biofilm formation,
      colonization, and biocontrol of B. cereus and that B. cereus wild-type strain 0-9
      may be an ideal biocontrol agent for controlling wheat sharp eyespot. 

PMID- 24750251
TI  - Filter neuroprotection of a single patent internal carotid artery during
      transapical aortic valve implantation.
AB  - The finding of a mobile calcific plaque attached to the aortic valve cusp during
      transcatheter aortic valve implantation (TAVI/TAVR) necessitated utilization of
      an embolic protection device, for cerebral protection. We report the urgent but
      successful deployment of such a filter in a patient with a single patent internal
      carotid artery. Although stroke rates observed in first-generation TAVI trials
      were higher than those reported following conventional open aortic valve
      replacement, adjunctive neuroprotective measures, particularly in patients with a
      large amount of threatened cerebral territory, may minimize potential neurologic
      injury.

PMID- 24750252
TI  - Seasonal variability in environmental tobacco smoke exposure in public housing
      developments.
AB  - The risk of tobacco smoking and second-hand smoke (SHS) exposure combined are the
      leading contributors to disease burden in high-income countries. Recent studies
      and policies are focusing on reducing exposure to SHS in multiunit housing (MUH),
      especially public housing. We examined seasonal patterns of SHS levels within
      indoor common areas located on Boston Housing Authority (BHA) properties. We
      measured weekly integrated and continuous fine particulate matter (PM2.5) and
      passive airborne nicotine in six buildings of varying building and occupant
      characteristics in summer 2012 and winter 2013. The average weekly indoor PM2.5
      concentration across all six developments was 9.2 MUg/m3, higher during winter
      monitoring period (10.3 MUg/m3) compared with summer (8.0 MUg/m3). Airborne
      nicotine concentrations ranged from no detection to about 5000 ng/m3 (mean 311
      ng/m3). Nicotine levels were significantly higher in the winter compared with
      summer (620 vs. 85 ng/m3; 95% CI: 72-998). Smoking-related exposures within
      Boston public housing vary by season, building types, and resident smoking
      policy. Our results represent exposure disparities that may contribute to health
      disparities in low-income communities and highlight the potential importance of
      efforts to mitigate SHS exposures during winter when outdoor-indoor exchange
      rates are low and smokers may tend to stay indoors. Our findings support the use
      of smoke-free policy as an effective tool to eliminate SHS exposure and protect
      non-smokers, especially residents of MUH.

PMID- 24750253
TI  - Elevated mean platelet volume is associated with silent cerebral infarction.
AB  - BACKGROUND: The presence of silent cerebral infarction (SCI) increases the risk
      of transient ischaemia attack, symptomatic stroke, cardiovascular disease and
      dementia. Mean platelet volume (MPV) is a surrogate marker of activated platelets
      and is considered a link between inflammation and thrombosis. In addition, MPV is
      a risk predictor for cardiovascular disease, stroke and overall vascular
      mortality. AIMS: The purpose of the study was to assess the MPV levels in SCI
      patients. METHODS: A cross-sectional study was conducted to evaluate the
      association between MPV and SCI in 2215 subjects (1385 men and 830 women).
      RESULTS: The participants with SCI had higher MPV levels than those without SCI
      (10.4 +/- 1.3 fL vs. 9.2 +/- 1.2 fL; P < 0.001). Moreover, the subjects with a
      high MPV had a higher prevalence of SCI. Multivariate logistic regression
      analyses revealed that the odds ratios and 95% confidence intervals for SCI
      according to MPV quartiles were 1.000, 2.131 (1.319-3.444), 3.015 (1.896-4.794),
      7.822 (4.874-12.554) respectively (P < 0.001). CONCLUSION: MPV is a novel index
      for SCI regardless of classical cardiovascular risk factors.

PMID- 24750254
TI  - Does Helicobacter pylori protect against eosinophilic esophagitis in children?
AB  - BACKGROUND: Helicobacter pylori infection and eosinophilic esophagitis (EoE) in
      children seem to have a reversed association with socioeconomic status (hygienic
      condition) and allergy conditions. While Hp infection (Hp) is highly associated
      with poor hygiene and/or poor socioeconomic status, but not with allergic
      conditions (asthma, rhinitis, etc.), EoE has the opposite epidemiological
      relationship (high association with allergy but low with low hygienic
      conditions). AIM: To investigate the association between Hp infection and EoE in
      children. METHODS: A retrospective chart review of all children who undergo the
      first upper endoscopy procedure in the gastroenterology clinic, between 2007 and
      2012, was performed. Demographic, endoscopic and histological data were
      collected. The data was divided into 4 diagnostic groups: Hp infection, EoE,
      reflux esophagitis, and children who had normal histology. The relationship
      between Hp positive children and the other groups was performed. RESULTS: A total
      of 966 charts were available for review. Esophagitis, idiopathic gastritis, EoE,
      and Hp infection were detected in 268 (28%), 480 (49%), 62 (6%), and 31 (3%)
      children, respectively. The mean age of the EoE group was significantly lower
      compared to all reference groups (p < .002), but no significant different was
      detected among the reference groups (gastritis, GERD, and Hp infection; p =
      1.00). Simple logistic regression analysis using Hp infection as a predictor for
      EoE did not find a significant relationship between these two variables (p-value
      = .471, OR = 0.478, 95% CI 0.06-3.56). However, multivariable logistic regression
      analysis between EoE and the reference groups indicated a significant negative
      relationship between Hp infection and EoE (p-value = .023, adjusted OR = 0.096,
      95%CI 0.013-0.72). Neither gastritis nor GER showed significant relationship with
      EoE (p-values are 1.000 and .992, respectively). CONCLUSION: A reversed
      association between Hp and EoE was found in a cohort of West Virginia children.
      The possible explanations for these findings are discussed.

PMID- 24750255
TI  - HLA-DQ polymorphisms with HBV infection: different outcomes upon infection and
      prognosis to lamivudine therapy.
AB  - Two recent genome-wide studies showed that the single-nucleotide polymorphisms in
      the HLA-DQ region (rs2856718 and rs9275572) were associated with chronic
      hepatitis B virus infection and chronic hepatitis C virus-associated
      hepatocellular carcinoma in Japanese patients. We tested the effects of the two
      single-nucleotide polymorphisms for all major HBV outcomes and lamivudine
      treatment in Han Chinese. A total of 1649 samples were enrolled, and peripheral
      blood samples were collected in this study. The single-nucleotide polymorphisms
      in the HLA-DQ region were genotyped using matrix-assisted laser
      desorption/ionization time of flight mass spectrometry. Our study demonstrated
      the clear relevance of HLA-DQ rs2856718 and rs9275572 with HBV susceptibility,
      natural clearance and HBV-associated HCC. HLA-DQ rs2856718G and rs9275572A were
      strongly associated with decreased risk of chronic HBV infection (odds ratio =
      0.641; P = 2.64 * 10(-4) ; odds ratio = 0.627, P = 7.22 * 10(-5) ) and HBV
      natural clearance (odds ratio = 0.610; P = 4.80 * 10(-4) ; odds ratio = 0.714, P
      = 0.013). Moreover, rs9275572A was also associated with development of cirrhosis
      and hepatocellular carcinoma (odds ratio = 0.632, P = 0.008). In addition, we
      showed for the first time to our knowledge that rs9275572 was a predictor for
      lamivudine therapy (viral response: odds ratio = 2.599, P = 4.43 * 10(-4) ;
      biochemical response: odds ratio = 2.279, P = 4.23 * 10(-4) ). Our study
      suggested that HLA-DQ loci were associated with both HBV clearance and HBV
      related diseases and outcomes of lamivudine treatment in Han Chinese.

PMID- 24750256
TI  - Rich analysis and rational models: inferring individual behavior from infant
      looking data.
AB  - Studies of infant looking times over the past 50 years have provided profound
      insights about cognitive development, but their dependent measures and analytic
      techniques are quite limited. In the context of infants' attention to discrete
      sequential events, we show how a Bayesian data analysis approach can be combined
      with a rational cognitive model to create a rich data analysis framework for
      infant looking times. We formalize (i) a statistical learning model, (ii) a
      parametric linking between the learning model's beliefs and infants' looking
      behavior, and (iii) a data analysis approach and model that infers parameters of
      the cognitive model and linking function for groups and individuals. Using this
      approach, we show that recent findings from Kidd, Piantadosi and Aslin (iv) of a
      U-shaped relationship between look-away probability and stimulus complexity even
      holds within infants and is not due to averaging subjects with different types of
      behavior. Our results indicate that individual infants prefer stimuli of
      intermediate complexity, reserving attention for events that are moderately
      predictable given their probabilistic expectations about the world.

PMID- 24750257
TI  - Anterior placentation as a risk factor for massive hemorrhage during cesarean
      section in patients with placenta previa.
AB  - AIM: In placenta previa (PP), anterior placentation, compared with posterior
      placentation, is reported to more frequently cause massive hemorrhage during
      cesarean section (CS). Whether this is due to the high incidence of placenta
      accreta, previous CS, or a transplacental approach in anterior placenta is
      unclear. We attempted to clarify this issue. MATERIAL AND METHODS: We
      retrospectively analyzed the relation between the bleeding amount during CS for
      PP and various factors that may cause massive hemorrhage (>2400 mL) (n = 205) in
      a tertiary center. If the preoperatively ultrasound-measured distance from the
      internal cervical ostium to the placental edge was longer in the uterine anterior
      wall than in the posterior wall, we defined it as anterior previa, and vice
      versa. RESULTS: Patients with accreta, previous CS, total previa, and anterior
      placentation bled significantly more than their counterparts. Multivariate
      logistic regression analysis showed that accreta (odds ratio [OR] 12.6), previous
      CS (OR 4.7), total previa (OR 4.1), and anterior placentation (OR 3.5) were
      independent risk factors of massive hemorrhage. CONCLUSIONS: Anterior
      placentation, namely, the placenta with a longer os-placental edge distance in
      the anterior wall than in the posterior wall, was a risk of massive hemorrhage
      during CS for PP.

PMID- 24750258
TI  - A role for FtsA in SPOR-independent localization of the essential Escherichia
      coli cell division protein FtsN.
AB  - FtsN is a bitopic membrane protein and the last essential component to localize
      to the Escherichia coli cell division machinery, or divisome. The periplasmic
      SPOR domain of FtsN was previously shown to localize to the divisome in a self
      enhancing manner, relying on the essential activity of FtsN and the peptidoglycan
      synthesis and degradation activities of FtsI and amidases respectively. Because
      FtsN has a known role in recruiting amidases and is predicted to stimulate the
      activity of FtsI, it follows that FtsN initially localizes to division sites in a
      SPOR-independent manner. Here, we show that the cytoplasmic and transmembrane
      domains of FtsN (FtsN(Cyto - TM)) facilitated localization of FtsN independently
      of its SPOR domain but dependent on the early cell division protein FtsA. In
      addition, SPOR-independent localization preceded SPOR-dependent localization,
      providing a mechanism for the initial localization of FtsN. In support of the
      role of FtsNCyto - TM in FtsN function, a variant of FtsN lacking the cytoplasmic
      domain localized to the divisome but failed to complement an ftsN deletion unless
      it was overproduced. Simultaneous removal of the cytoplasmic and SPOR domains
      abolished localization and complementation. These data support a model in which
      FtsA-FtsN interaction recruits FtsN to the divisome, where it can then stimulate
      the peptidoglycan remodelling activities required for SPOR-dependent
      localization.

PMID- 24750259
TI  - The effect of maternal and paternal immune challenge on offspring immunity and
      reproduction in a cricket.
AB  - Trans-generational immune priming is the transmission of enhanced immunity to
      offspring following a parental immune challenge. Although within-generation
      increased investment into immunity demonstrates clear costs on reproductive
      investment in a number of taxa, the potential for immune priming to impact on
      offspring reproductive investment has not been thoroughly investigated. We
      explored the reproductive costs of immune priming in a field cricket,
      Teleogryllus oceanicus. To assess the relative importance of maternal and
      paternal immune status, mothers and fathers were immune-challenged with live
      bacteria or a control solution and assigned to one of four treatments in which
      one parent, neither or both parents were immune-challenged. Families of offspring
      were reared to adulthood under a food-restricted diet, and approximately 10
      offspring in each family were assayed for two measures of immunocompetence. We
      additionally quantified offspring reproductive investment using sperm viability
      for males and ovary mass for females. We demonstrate that parental immune
      challenge has significant consequences for the immunocompetence and, in turn,
      reproductive investment of their male offspring. A complex interaction between
      maternal and paternal immune status increased the antibacterial immune response
      of male offspring. This increased immune response was associated with a reduction
      in son's sperm viability, implicating a trans-generational resource trade-off
      between investment into immunocompetence and reproduction. Our data also show
      that these costs are sexually dimorphic, as daughters did not demonstrate a
      similar increase in immunity, despite showing a reduction in ovary mass. 

PMID- 24750260
TI  - Growing teratoma syndrome: clinical and radiographic characteristics.
AB  - OBJECTIVES: To present an overview of our surgical experience in the management
      of growing teratoma syndrome. METHODS: A retrospective analysis of all patients
      undergoing post-chemotherapy retroperitoneal lymphadenectomy between November
      2005 and February 2012 revealed 15 patients who met the criteria for growing
      teratoma syndrome. Their clinical data, imaging characteristics, and surgical and
      oncological outcomes were reviewed. RESULTS: The median age at diagnosis was 23
      years. Primary testis tumors included non-seminomatous germ cell tumor in 12 of
      15 patients, seminoma in two of 15 patients and hemorrhagic mass in one patient.
      Mature teratoma was present in just six (40%) of the orchiectomy specimens. All
      patients received preoperative chemotherapy. On imaging, the median size of the
      largest retroperitoneal mass was 7 cm (range 3.9-24.5 cm). The median rate of
      linear growth was 0.5 cm/month (range 0.03-2.9), and the increase in volume was
      9.2 cm(3) /month. All tumors were found to have cystic and necrotic components.
      Median operative time was 6.2 h (range 4.2-15.2 h). Estimated blood loss was 600
      mL (range 100-7000 mL), and median length of stay was 5 days (range 3-19 days).
      Four patients required resection of non-retroperitoneal growing teratoma masses
      after post-chemotherapy retroperitoneal lymphadenectomy to achieve tumor-free
      status. There were two minor (Clavien I-II) and two major postoperative
      complications (Clavien >=III). All patients are alive and disease free with a
      median duration of follow-up of 8 months (range 1-64 months). CONCLUSIONS:
      Growing teratoma syndrome tumors vary in their growth rate, but they all appear
      to have cystic features with necrosis elements on radiographic evaluation.
      Aggressive surgical excision is associated with excellent outcomes.

PMID- 24750261
TI  - The role of pain modulators in esophageal disorders - no pain no gain.
AB  - Pain modulators have been primarily used for the management of functional
      esophageal disorders. Recently, these drugs have also been used for the
      management of other esophageal disorders, such as non-erosive reflux disease, the
      hypersensitive esophagus, and heartburn that is not responsive to proton pump
      inhibitor treatment. Several etiologies have been identified in patients with
      functional esophageal disorders, and these include esophageal hypersensitivity
      due to peripheral and/or central sensitisation, altered central processing of
      peripheral stimuli, altered autonomic activity, and psychological comorbidity
      such as depression and anxiety. Different antidepressants have been used as pain
      modulators and have demonstrated a beneficial effect on patients with the
      aforementioned esophageal disorders. Tricyclic antidepressants are the most
      commonly used class of drugs in clinical practice. Other antidepressants that
      have been used, some with more clinical success than others, include selective
      serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, and
      trazodone. Other medications that have been used as pain modulators in esophageal
      disorders include adenosine antagonists, serotonin agonists, antiepileptics, and
      medications that ameliorate peripheral neuropathy. The mechanism by which many of
      the pain modulators confer their visceral analgesic effect remains to be fully
      elucidated. Regardless, their role and value in treating esophageal disorders
      have markedly increased in the last decade. 

PMID- 24750262
TI  - Fluctuations in vital signs and behavioural responses of brain surgery patients
      in the Intensive Care Unit: are they valid indicators of pain?
AB  - AIM: To examine the validity of behaviours and fluctuations in vital signs for
      pain assessment of postbrain surgery adults in the neurosurgical intensive care
      unit. BACKGROUND: Many patients in an intensive care unit may be unable to self
      report their pain. In such cases, the use of observable indicators is
      recommended. Very little research has explored the validity of the use of
      behaviours and vital signs for pain assessment of neurocritically ill patients.
      DESIGN: Prospective repeated-measure within-subject observational design.
      METHODS: A total of 43 postbrain surgery patients were video recorded before,
      during and 15 minutes after a non-nociceptive (non-invasive blood pressure cuff
      inflation) and a nociceptive (turning) procedures. Their behaviours and vital
      signs were collected with a pre-tested behavioural checklist and a data
      collection computer connected to the bedside monitor. The patients' self-report
      of pain was obtained whenever possible. Data were collected between June-December
      in 2011. RESULTS: A larger number of pain-related behaviours were exhibited by
      participants during the nociceptive procedure compared with the non-nociceptive
      procedure supporting discriminant validation. Among vital signs, only respiratory
      rate differed significantly between the two procedures. Regarding criterion
      validation, only behaviours were positively correlated with self-reports of pain.
      CONCLUSION: Behaviours were found valid indicators of pain in neurocritically ill
      patients after elective brain surgery. Fluctuations in vital signs may suggest
      the presence of pain, but their validity for such use is not supported. They
      should only be used in combination with other validated pain assessment methods.

PMID- 24750263
TI  - Buffer nitrogen solubility, in vitro ruminal partitioning of nitrogen and in
      vitro ruminal biological activity of tannins in leaves of four fodder tree
      species.
AB  - This study explores the chemical composition, buffer N solubility, in vitro
      ruminal N degradability and in vitro ruminal biological activity of tannins in
      leaves from Gliricidia sepium, Leucaena leucocephala, Morus alba and Trichanthera
      gigantea trees. These tree leaves are a potential protein source for ruminants,
      but their site-influenced nutritive value is largely unknown. Leucaena
      leucocephala leaves had the highest N content (42.1 g/kg DM), while T. gigantea
      leaves had the least (26.1 g/kg DM). Leucaena leucocephala had the highest buffer
      solubility index (20%), while 10% of the total N in leaves of the other three
      species was soluble. The rapidly fermentable N fraction 'a' was highest in M.
      alba leaves (734.9 g/kg DM) and least in T. gigantea leaves (139.5 g/kg DM). The
      rate of fermentation (c) was highest for M. alba (7%/hours) leaves. No
      significant correlations were recorded between buffer solubility index of N and
      in vitro ruminal N degradability parameters: a, b, and c. The highest response to
      tannin inactivation using polyethylene glycol, in terms of percentage increase in
      36-hours cumulative gas production, was recorded in M. alba (39%) and T. gigantea
      (38%) leaves. It was concluded that buffer solubility of N is not a good
      indicator of ruminal N degradation in the leaves of these tree species. Leaves of
      M. alba could be more valuable as a source of rapidly fermentable N when animals
      are offered low-protein, high-fibre diets compared with other tree species
      evaluated in the current study. However, when feeding M. alba leaves, the role of
      tannins must be considered because these secondary plant compounds showed
      significant in vitro ruminal biological activity. 

PMID- 24750264
TI  - Comparison of two modalities: a novel technique, 'chromohysteroscopy', and blind
      endometrial sampling for the evaluation of abnormal uterine bleeding.
AB  - AIM: The objective of this study was to compare classical blind endometrial
      tissue sampling with hysteroscopic biopsy sampling following methylene blue
      dyeing in premenopausal and postmenopausal patients with abnormal uterine
      bleeding. MATERIAL AND METHODS: A prospective case-control study was carried out
      in the Office Hysteroscopy Unit. Fifty-four patients with complaints of abnormal
      uterine bleeding were evaluated. Data of 38 patients were included in the
      statistical analysis. Three groups were compared by examining samples obtained
      through hysteroscopic biopsy before and after methylene blue dyeing, and
      classical blind endometrial tissue sampling. First, uterine cavity was evaluated
      with office hysteroscopy. Methylene blue dye was administered through the
      hysteroscopic inlet. Tissue samples were obtained from stained and non-stained
      areas. Blind endometrial sampling was performed in the same patients immediately
      after the hysteroscopy procedure. The results of hysteroscopic biopsy from
      methylene blue stained and non-stained areas and blind biopsy were compared.
      RESULTS: No statistically significant differences were determined in the
      comparison of biopsy samples obtained from methylene-blue stained, non-stained
      areas and blind biopsy (P > 0.05). CONCLUSIONS: We suggest that
      chromohysteroscopy is not superior to endometrial sampling in cases of abnormal
      uterine bleeding. Further studies with greater sample sizes should be performed
      to assess the validity of routine use of endometrial dyeing.

PMID- 24750265
TI  - Characterisation of the inflammatory cytokine response to anthelmintic treatment
      in ponies.
AB  - REASONS FOR PERFORMING STUDY: Anthelmintic treatments have been associated with
      local inflammatory reactions. Since each class of anthelmintic has unique
      mechanisms of action affecting different subpopulations of parasites, we
      hypothesised that they will also induce characteristic proinflammatory responses.
      OBJECTIVES: To determine the effect of anthelmintic class on the proinflammatory
      response post treatment. STUDY DESIGN: Ponies naturally infected with
      cyathostomins and other parasites after pasture grazing were left untreated or
      treated with representatives of 3 different classes of anthelmintics:
      fenbendazole (benzimidazole); pyrantel tartrate (pyrimidine); and moxidectin
      (macrocyclic lactone). All were monitored for the expression of proinflammatory
      genes in the peripheral blood using real-time PCR. METHODS: The ponies were
      divided into 4 treatment groups: Group 1 (n = 4) were untreated controls; Group 2
      (n = 5) received 5 daily doses of fenbendazole (10 mg/kg bwt); Group 3 (n = 4)
      received daily treatment of pyrantel tartrate 2* (2.65 mg/kg bwt); and Group 4 (n
      = 5) received a single dose of moxidectin (400 MUg/kg bwt). Blood samples were
      collected daily for 2 weeks to determine the effect of deworming on
      proinflammatory gene expression. Faecal egg counts were used to evaluate the
      efficacy of each drug. RESULTS: While treatment with the benzimidazole
      significantly reduced egg counts up to 14 days post treatment, it also stimulated
      proinflammatory gene expression. Treatment with pyrantel salt also reduced faecal
      egg counts with less of a proinflammatory response. Treatment with the
      macrocyclic lactone was the most successful in reducing faecal egg counts and
      produced no signs of increased proinflammatory cytokine expression. CONCLUSIONS:
      This study revealed pronounced differences in the cytokine responses to
      anthelmintic treatment. This inflammatory reaction may play a role in the
      development of parasitic disease post anthelmintic treatment.

PMID- 24750266
TI  - Effect of a novel temperature-controlled laminar airflow device on personal
      breathing zone aeroallergen exposure.
AB  - Temperature-controlled laminar airflow improves symptoms in atopic asthmatics,
      but its effects on personal allergen exposure are unknown. We aimed to evaluate
      its effects on personal cat allergen and particulate exposures in a simulated
      bedroom environment. Five healthy volunteers lay under an active and an inactive
      temperature-controlled laminar airflow device for 175 min, in a simulated bedroom
      containing bedding from a cat owner. Total airborne particles (>=0.5 - >=10 MUm
      diameter) were quantified with a laser particle counter. Airborne allergen was
      sampled with Institute of Occupational Medicine filters. Inhaled exposure was
      sampled with nasal air samplers. Allergen-containing particles were quantified by
      immunoassay. Treatment reduced total airborne particles (>0.5 MUm diameter) by
      >99% (P < 0.001) and reduced airborne allergen concentration within the breathing
      zone (ratio of median counts = 30, P = 0.043). Treatment reduced inhaled allergen
      (ratio of median counts = 7, P = 0.043). Treatment was not associated with a
      change in airborne allergen concentration outside of the breathing zone (P =
      0.160). Temperature-controlled laminar airflow treatment of individuals in an
      allergen-rich experimental environment results in significant reductions in
      breathing zone allergenic and non-allergenic particle exposure, and in inhaled
      cat allergen exposure. These findings may explain the clinical benefits of
      temperature-controlled laminar airflow. 

PMID- 24750268
TI  - The effects of light therapy on depression and sleep disruption in older adults
      in a long-term care facility.
AB  - This study aims to evaluate the effect of light therapy on depression and sleep
      disruption in older adults residing in a long-term care facility. Psychological
      morbidity is a problem commonly seen in older adults residing in long-term care
      facilities. Limited research has addressed the effect of light therapy on
      depression in this population. A quasi-experimental pretest and posttest design
      was used. Thirty-four participants in the experimental group received light
      therapy by sitting in front of a 10000-lux light box 30 min in the morning, three
      times a week for 4 weeks. Thirty-one participants in the control group received
      routine care without light therapy. Depression was measured by Geriatric
      Depression Scale-Short Form at baseline and week 4. After receiving 4 weeks of
      light therapy, the mean depression score in the experimental group decreased from
      7.24 (SD3.42) at pretest to 5.91 (SD 3.40) at posttest, and had a significant
      reduction (t = 2.22, P = 0.03). However, there was no significant difference in
      depression score and sleep disruption between the experimental group and control
      group. Light therapy might have the potential to reduce depressive symptoms and
      sleep disruption and may be a viable intervention to improve mental health of
      older adults in the long-term care facilities. 

PMID- 24750267
TI  - Effect of dietary nonstructural carbohydrate content on activation of 5'
      adenosine monophosphate-activated protein kinase in liver, skeletal muscle, and
      digital laminae of lean and obese ponies.
AB  - BACKGROUND: In EMS-associated laminitis, laminar failure may occur in response to
      energy failure related to insulin resistance (IR) or to the effect of
      hyperinsulinemia on laminar tissue. 5'-Adenosine-monophosphate-activated protein
      kinase (AMPK) is a marker of tissue energy deprivation, which may occur in IR.
      HYPOTHESIS/OBJECTIVES: To characterize tissue AMPK regulation in ponies subjected
      to a dietary carbohydrate (CHO) challenge. ANIMALS: Twenty-two mixed-breed
      ponies. METHODS: Immunohistochemistry and immunoblotting for total AMPK and
      phospho(P)-AMPK and RT-qPCR for AMPK-responsive genes were performed on laminar,
      liver, and skeletal muscle samples collected after a 7-day feeding protocol in
      which ponies stratified on body condition score (BCS; obese or lean) were fed
      either a low-CHO diet (ESC + starch, approximately 7% DM; n = 5 obese, 5 lean) or
      a high-CHO diet (ESC + starch, approximately 42% DM; n = 6 obese, 6 lean).
      RESULTS: 5'-Adenosine-monophosphate-activated protein kinase was immunolocalized
      to laminar keratinocytes, dermal constituents, and hepatocytes. A high-CHO diet
      resulted in significantly decreased laminar [P-AMPK] in lean ponies (P = .03),
      but no changes in skeletal muscle (lean, P = .33; obese, P = .43) or liver (lean,
      P = .84; obese, P = .13) [P-AMPK]. An inverse correlation existed between [blood
      glucose] and laminar [P-AMPK] in obese ponies on a high-CHO diet. CONCLUSIONS AND
      CLINICAL IMPORTANCE: Laminar tissue exhibited a normal response to a high-CHO
      diet (decreased [P-AMPK]), whereas this response was not observed in liver and
      skeletal muscle in both lean (skeletal muscle, P = .33; liver, P = .84) and obese
      (skeletal muscle, P = .43; liver, P = .13) ponies.

PMID- 24750269
TI  - Unusual case of linear anetoderma in children.

PMID- 24750270
TI  - Contrast ratio of six zirconia-based dental ceramics.
AB  - PURPOSE: The objective of this study was to determine the effect of thickness and
      brands on the contrast ratio of six zirconia dental ceramics. MATERIALS AND
      METHODS: Six brands of yttria-stabilized tetragonal zirconia polycrystalline (Y
      TZP) ceramics (ZENO(r) Translucent, LavaTM Plus High Translucency, inCoris TZI,
      Cercon(r) Base, Zeno(r)Zr, LavaTM) were used in this study. Disc-shaped specimens
      with 15 mm diameter were prepared in five thickness levels (0.3, 0.6, 0.9, 1.2,
      1.5 mm, n = 10) for each brand. The contrast ratio (CR = Y(b) /Y(w) ) was
      determined from the luminous reflectance over black (Y(b) ) and white (Y(w) )
      backgrounds using a spectrophotometer. Two-way ANOVA was performed to determine
      the significant differences among thicknesses and brands at alpha = 0.05.
      RESULTS: The mean contrast ratio values of six zirconia ceramics were
      significantly different and influenced by both the thickness and brand. The mean
      contrast ratio values of all groups increased as their thickness increased from
      0.3 to 1.5 mm. inCoris TZI was the most translucent, with the lowest contrast
      ratio at a thickness of 0.6 to 1.5 mm. The mean contrast ratio values of LavaTM
      and LavaTM Plus were significantly lower than those of Zeno(r)Zr, ZENO(r)
      Translucent, and Cercon(r) Base. CONCLUSIONS: The thickness and brands had
      significant effects on the contrast ratio of six zirconia dental ceramics. The
      mean contrast ratio values of inCoris TZI, LavaTM, and LavaTM Plus High
      Translucency were significantly lower than those of Cercon(r) Base, Zeno(r), and
      ZENO(r) Translucent at all thicknesses.

PMID- 24750271
TI  - Efficacy and safety of growth hormone treatment in adults with growth hormone
      deficiency: a systematic review of studies on morbidity.
AB  - Due to the positive effects demonstrated in randomized clinical trials on
      cardiovascular surrogate markers and bone metabolism, a positive effect of growth
      hormone (GH) treatment on clinically relevant end-points seems feasible. In this
      review, we discuss the long-term efficacy and safety of GH treatment in adult
      patients with growth hormone deficiency (GHD) with emphasis on morbidity: fatal
      and nonfatal cardiovascular disease (CVD) and stroke, fractures, fatal and
      nonfatal malignancies and recurrences, and diabetes mellitus. A positive effect
      of GH treatment on CVD and fracture risk could be concluded, but study design
      limitations have to be considered. Stroke and secondary brain tumours remained
      more prevalent. However, other contributing factors have to be taken into
      account. Regrowth and recurrences of (peri)pituitary tumours were not increased
      in patients with GH treatment compared to similar patients without GH treatment.
      All fatal and nonfatal malignancies were not more prevalent in GH-treated adults
      compared to the general population. However, follow-up time is still relatively
      short. The studies on diabetes are difficult to interpret, and more evidence is
      awaited. In clinical practice, a more individualized assessment seems
      appropriate, taking into consideration the underlying diagnosis of GHD, other
      treatment regimens, metabolic profile and the additional beneficial effects of GH
      set against the possible risks. Large and thoroughly conducted observational
      studies are needed and seem the only feasible way to inform the ongoing debate on
      health care costs, drug safety and clinical outcomes. 

PMID- 24750272
TI  - Pancreatic neuroendocrine tumour grading on endoscopic ultrasound-guided fine
      needle aspiration: high reproducibility and inter-observer agreement of the Ki-67
      labelling index.
AB  - OBJECTIVES: Assessment of proliferation by the Ki-67 labelling index (Ki67-LI) is
      an important parameter of pancreatic neuroendocrine tumour (pNET) prognosis on
      resection specimens. Ki67-LI values for grading are not fully established on
      endoscopic ultrasound-guided fine needle aspiration (EUS-FNA). The aim of the
      study was to determine the accuracy of Ki67-LI on EUS-FNA to predict a final
      grade of pNET and to analyse the relationship between cytological grading and
      progression-free survival (PFS). METHODS: Between 1996 and 2010, 46 pNETs (33
      were resected) from 45 patients were diagnosed by EUS-FNA. Ki67-LI was evaluated
      on cytological and histological material for each tumour and classified according
      to the 2010 WHO grading system. RESULTS: A very good inter-observer agreement for
      Ki67-LI on EUS-FNA and surgical specimens, respectively, were obtained.
      Discrepancies were observed between histology and cytology, especially in grade 2
      (G2) tumours, where cytology underestimated grading owing to tumour
      heterogeneity. Still, EUS-FNA was able to distinguish a poor prognostic group, as
      the actuarial PFS of cytological (c) G3 tumours was 10 +/- 4 months versus 29 +/-
      7 and 68 +/- 10 for cG2 and cG1 tumours, respectively (P < 0.0001). CONCLUSION:
      This study attests the reproducibility of Ki67-LI of pNETs whether counted on
      cytology or histology with a very good inter-observer correlation. Determination
      of Ki67-LI on EUS-FNA of pNETs should be included systematically in their
      prognostic work-up.

PMID- 24750274
TI  - Neutrophil-lymphocyte ratio: a novel predictor for short-term prognosis in acute
      on-chronic hepatitis B liver failure.
AB  - Acute-on-chronic hepatitis B liver failure (ACHBLF) has a poor prognosis in
      patients with hepatitis B virus infection. The role of the neutrophil-lymphocyte
      ratio (NLR), which reflects the inflammatory status of the patient before
      treatment, has never been studied in this setting. To investigate the predictive
      value of NLR in patients with ACHBLF, a retrospective cohort with 216 patients
      and a prospective validation cohort with 73 patients were recruited. Multivariate
      analyses showed that total bilirubin (TBIL), NLR, age and model for end-stage
      liver disease (MELD) score had prognostic significance for survival. Both NLR
      (0.781) and MELD score (0.744) had higher ROC curves, which differed
      significantly from those for age (0.615) and TBIL (0.691), but not from each
      other (P = 0.94). NLR <= 2.36 predicted lower mortality (with 91.6% sensitivity
      and 86.0% negative predictive value), and NLR >6.12 was a warning sign for higher
      mortality risk (with 90.1% specificity and 80.3% positive predictive value).
      These results demonstrated that pretreatment NLR was associated with the
      prognosis of patients with ACHBLF, and elevated NLR predicted poor outcome within
      8 weeks. We suggest that NLR cut-offs of <= 2.36 and >6.12 are powerful markers
      for predicting mortality in ACHBLF.

PMID- 24750273
TI  - A conserved and essential basic region mediates tRNA binding to the Elp1 subunit
      of the Saccharomyces cerevisiae Elongator complex.
AB  - Elongator is a conserved, multi-protein complex discovered in Saccharomyces
      cerevisiae, loss of which confers a range of pleiotropic phenotypes. Elongator in
      higher eukaryotes is required for normal growth and development and a mutation in
      the largest subunit of human Elongator (Elp1) causes familial dysautonomia, a
      severe recessive neuropathy. Elongator promotes addition of mcm(5) and ncm(5)
      modifications to uridine in the tRNA anticodon 'wobble' position in both yeast
      and higher eukaryotes. Since these modifications are required for the tRNAs to
      function efficiently, a translation defect caused by hypomodified tRNAs may
      therefore underlie the variety of phenotypes associated with Elongator
      dysfunction. The Elp1 carboxy-terminal domain contains a highly conserved
      arginine/lysine-rich region that resembles a nuclear localization sequence (NLS).
      Using alanine substitution mutagenesis, we show that this region is essential for
      Elongator's function in tRNA wobble uridine modification. However, rather than
      acting to determine the nucleo-cytoplasmic distribution of Elongator, we find
      that the basic region plays a critical role in a novel interaction between tRNA
      and the Elp1 carboxy-terminal domain. Thus the conserved basic region in Elp1 may
      be essential for tRNA wobble uridine modification by acting as tRNA binding
      motif. 

PMID- 24750275
TI  - First detected Helicobacter pylori infection in infancy modifies the association
      between diarrheal disease and childhood growth in Peru.
AB  - BACKGROUND: In endemic settings, Helicobacter pylori infection can occur shortly
      after birth and may be associated with a reduction in childhood growth. MATERIALS
      AND METHODS: This study investigated what factors promote earlier age of first H.
      pylori infection and evaluated the role of H. pylori infection in infancy (6-11
      months) versus early childhood (12-23 months) on height. We included 183 children
      near birth from a peri-urban shanty town outside of Lima, Peru. Field-workers
      collected data on socioeconomic status (SES), daily diarrheal and breast-feeding
      history, antibiotic use, anthropometrics, and H. pylori status via carbon 13
      labeled urea breath test up to 24 months after birth. We used a proportional
      hazards model to assess risk factors for earlier age at first detected infection
      and linear mixed-effects models to evaluate the association of first detected H.
      pylori infection during infancy on attained height. RESULTS: One hundred and
      forty (77%) were infected before 12 months of age. Lower SES was associated with
      earlier age at first detected H. pylori infection (low vs middle-to-high SES
      Hazard ratio (HR) 1.59, 95% CI 1.16, 2.19; p = .004), and greater exclusive
      breast-feeding was associated with reduced likelihood (HR 0.63, 95% CI 0.40,
      0.98, p = .04). H. pylori infection in infancy was not independently associated
      with growth deficits (p = .58). However, children who had their first detected H.
      pylori infection in infancy (6-11 months) versus early childhood (12-23 months)
      and who had an average number of diarrhea episodes per year (3.4) were
      significantly shorter at 24 months (-0.37 cm, 95% CI, -0.60, -0.15 cm; p = .001).
      DISCUSSION: Lower SES was associated with a higher risk of first detected H.
      pylori infection during infancy, which in turn augmented the adverse association
      of diarrheal disease on linear growth.

PMID- 24750276
TI  - Adverse drug events are a major cause of acute medical admission.
AB  - BACKGROUND: Adverse drug events (ADE) contribute significantly to hospital
      admissions. Prospective New Zealand data are scant, and the ability of clinical
      coding to identify ADE associated admissions is uncertain. Outcomes after
      cessation of causative medications are unknown. AIMS: To assess the frequency,
      nature and causality of ADE associated with acute admissions to General Medicine
      at Christchurch Hospital. METHODS: Prospective observational study of patients
      admitted to our medical team over 20 weeks. RESULTS: Of 336 admissions, 96
      (28.6%) were ADE related. Sixty-five (19.3%) were caused by an ADE, and 31 (9.2%)
      were contributed to by an ADE. The mean age of non-ADE patients was 64.3 years
      (range 16-91), which was similar to the mean age of ADE patients (65.9 years; 21
      92). However, if intentional overdoses and recreational drug use were excluded,
      ADE patients were significantly older at 72.4 years (21-92) (P = 0.0007). ADE
      patients took more regular medications on admission (mean 6.6, range 0-22) than
      non-ADE patients (mean 5.0, 0-18), (P = 0.003). The average length of stay was
      similar. The commonest medications implicated were vasodilators, psychotropics
      and diuretics. The most common adverse effects were postural hypotension and/or
      vasovagal syncope (29% of ADE), intentional overdoses and recreational drug use
      (15%) and acute renal failure and/or clinical dehydration (10%). Seventy-six
      patients had culprit medications stopped or reduced, and this potentially
      contributed to six readmissions. Coding identified 61% of ADE associated
      admissions. CONCLUSION: ADE are a common cause of hospital admission. The most
      frequent problems are postural hypotension and vasovagal syncope, intentional
      drug misuse and dehydration.

PMID- 24750277
TI  - Evidence of trade-offs shaping virulence evolution in an emerging wildlife
      pathogen.
AB  - In the mid-1990s, the common poultry pathogen Mycoplasma gallisepticum (MG) made
      a successful species jump to the eastern North American house finch Haemorhous
      mexicanus (HM). Subsequent strain diversification allows us to directly quantify,
      in an experimental setting, the transmission dynamics of three sequentially
      emergent geographic isolates of MG, which differ in the levels of pathogen load
      they induce. We find significant among-strain variation in rates of transmission
      as well as recovery. Pathogen strains also differ in their induction of host
      morbidity, measured as the severity of eye lesions due to infection.
      Relationships between pathogen traits are also investigated, with transmission
      and recovery rates being significantly negatively correlated, whereas
      transmission and virulence, measured as average eye lesion score over the course
      of infection, are positively correlated. By quantifying these disease-relevant
      parameters and their relationships, we provide the first analysis of the trade
      offs that shape the evolution of this important emerging pathogen. 

PMID- 24750278
TI  - Optimization of 2,3-butanediol production by Enterobacter cloacae in simultaneous
      saccharification and fermentation of corncob residue.
AB  - Corncob residue, a waste in xylose or xylitol production, was utilized to produce
      2,3-butanediol (2,3-BD) via simultaneous saccharification and fermentation (SSF).
      This study developed the optimal conditions for production of 2,3-BD by using a
      heat-resistant strain, Enterobacter cloacae UV4, to perform SSF of the corncob
      residue. Urea, lactic acid, sodium citrate, and MgSO4 , selected by the Plackett
      Burman experiment, were determined to be significant independent variables to
      conduct the response surface experiment. With the optimized medium, a total
      production of 28.923 g/L for 2,3-BD and acetoin (BA) was obtained at 60 H.
      Furthermore, 43.162 g/L of BA production and 0.553 g/L/H of productivity were
      obtained by fed-batch SSF, which was 0.424 g diol/g consumed corncob residue. The
      results suggest that the waste corncob residue could be used as an available
      substrate for the production of 2,3-BD by E. cloacae UV4, as well as a potential
      resource to improve the economics of microbial compound production. 

PMID- 24750279
TI  - A diagnostic evaluation of real-time PCR, fluorescent antibody and microscopic
      agglutination tests in cases of equine leptospiral abortion.
AB  - REASONS FOR PERFORMING STUDY: A comprehensive evaluation of the real-time PCR
      assay for leptospirosis in comparison with other diagnostic assays on a large
      scale basis is fundamental in validating the assay and determining the causes of
      equine abortions. OBJECTIVES: To compare and evaluate the diagnostic value of
      real-time PCR assay for leptospirosis with traditional methods in equine
      leptospiral abortions. STUDY DESIGN: Cross-sectional observational study.
      METHODS: A Leptospira spp. fluorescent antibody test (FAT), microscopic
      agglutination test (MAT) and real-time PCR (targeting the LipL32 gene) were
      compared and evaluated in equine fetal necropsy specimens (placenta, kidney,
      liver and heart blood) and maternal serum (when available) in 339 equine fetuses.
      RESULTS: From a total of 339 equine fetuses necropsied, 21 cases (6.19%) were
      diagnosed as leptospiral abortion. The majority of leptospiral abortions occurred
      in January (8 cases) and February (5 cases). Real-time PCR detected 21 of 21
      cases, whereas MAT and FAT detected 19 and 18 (including 2 suspicious cases)
      cases, respectively. Comparing tissues, placenta yielded somewhat similar cycle
      of threshold values by real-time PCR compared with kidney, whereas kidney was the
      best specimen for the diagnosis of leptospirosis by the FAT test. In all MAT
      positive cases, the predominant titre in fetal heart blood was to serovar Pomona
      (ranging 1:100 to 1:204,800) with little or no cross-reaction to serovar
      Grippotyphosa. CONCLUSIONS: The results indicate that real-time PCR is an
      effective method for the diagnosis of leptospiral abortion in horses. However,
      MAT should continue to be used in clinical cases for serovar determination.

PMID- 24750280
TI  - Fetal heart rate pattern interpretation in the second stage of labor using the
      five-tier classification: impact of the degree and duration on severe fetal
      acidosis.
AB  - AIM: The aim of this study was to clarify the association between fetal heart
      rate (FHR) tracing interpretation levels in the second stage of labor and poor
      fetal acid-base balance. MATERIAL AND METHODS: The database at one tertiary
      hospital in Nagoya, Japan, was retrospectively reviewed for women with singleton
      fetuses in cephalic presentation and vaginal labor at >=37 + 0 gestational weeks
      between 1 June 2011 and 30 April 2012. Continuous FHR tracings in the second
      stage of labor were subdivided into 15-min intervals, each of which we called a
      window, from the beginning of labor through delivery, and were assessed according
      to the five-tier classification proposed by the Japan Society of Obstetrics and
      Gynecology, in which level 1 is normal, level 2 is subnormal, and levels 3-5 are
      abnormal patterns. RESULTS: In total, 777 parturient women were eligible for the
      study protocol. The numbers of women with maximal levels of 1, 2, 3, 4, and 5
      were 3, 77, 341, 349, and 7, respectively. No cases of severe fetal acidosis (pH
      < 7.0 or base excess <-12 mmol/L) were recorded when the maximal levels were
      below 3. Both the pH and base excess of the umbilical artery decreased with
      higher levels of FHR tracings interpretation (P < 0.001). Both the summations of
      level-4 windows and level-3 and level-4 windows were significantly higher in
      women with severe fetal acidosis than in women without (P < 0.001), indicating
      that the duration of abnormal levels is associated with severe fetal acidosis.
      CONCLUSIONS: Both the degree and duration of FHR tracing abnormalities correlate
      with severe fetal acidosis.

PMID- 24750281
TI  - The proportion of cancellous bone as predictive factor for early marginal bone
      loss around implants in the posterior part of the mandible.
AB  - AIM: This study envisaged to explain early marginal bone loss (first years of
      function) around implants in the posterior area of the mandible by the local bone
      quality (ratio cortical vs. cancellous bone). MATERIAL AND METHODS: Four hundred
      and twenty-three Branemark MKIII implants inserted in the posterior region of the
      mandible were examined, retrospectively, on intra-oral radiographs taken at
      abutment connection, and 1 and 3-4 years after loading. The quality of the bone
      was assessed on cone beam or multi-slice CTs. The bone quality was determined by
      the relative proportions of cortical and trabecular bone at the insertion site.
      Cortical bone was defined as a clearly white structure without a trabecular
      pattern. Trabecular bone was defined as the structure between the two cortical
      plates. The width of both structures was measured at 1, 3, 5, and 7 mm away from
      the crest of the alveolar bone and converted in to relative proportions. Other
      parameters (smoking, history of periodontitis, dehiscence, pre-tapping, submerged
      healing, etc.) were retrieved from the patients record. RESULTS: At abutment
      connection, the mesial and distal marginal bone level was located 0.7 (+/-0.7)
      and 0.8 (+/-0.7) mm apically to the implant-abutment junction. At 1 year and 3-4
      years of loading implants placed in a mandible consisting of <30% of cancellous
      bone had lost 1.49 and 1.83 mm, respectively. Implants placed in jawbone
      consisting of more than 60% of cancellous bone lost 0.74 and 0.91 mm after 1 year
      and 3-4 years of loading. The bone-level changes (both first year as well as
      after 3-4 years) were significantly less when the implant was placed in sites
      with a higher proportion of cancellous bone. Other parameters were significantly
      less important. CONCLUSIONS: Very cortical bone could jeopardize the long-term
      stability of the marginal bone surrounding implants placed in the posterior
      region of the mandible. A correlation between marginal bone loss and the
      proportion of cortical bone was demonstrated around Branemark implants. At
      present, no comparable studies are available, and therefore, it cannot be
      excluded that similar events take place around other implant systems.

PMID- 24750282
TI  - Diarrhea caused by viruses in transplant recipients.
AB  - Diarrhea is a common complication after solid organ transplantation, and viruses
      are emerging as important but underestimated causative agents. Viral infections
      in solid organ transplant (SOT) recipients can result in severe and prolonged
      diarrhea with significant patient morbidity and graft complications.
      Cytomegalovirus remains the most common of the viruses to cause diarrhea, but
      other viruses are being increasingly recognized, including norovirus, rotavirus,
      and adenovirus. This article reviews the epidemiology, clinical presentation,
      diagnosis, management, and outcomes of these viral causes of diarrhea in SOT
      patients. 

PMID- 24750283
TI  - Genomic predictions across Nordic Holstein and Nordic Red using the genomic best
      linear unbiased prediction model with different genomic relationship matrices.
AB  - This study investigated genomic predictions across Nordic Holstein and Nordic Red
      using various genomic relationship matrices. Different sources of information,
      such as consistencies of linkage disequilibrium (LD) phase and marker effects,
      were used to construct the genomic relationship matrices (G-matrices) across
      these two breeds. Single-trait genomic best linear unbiased prediction (GBLUP)
      model and two-trait GBLUP model were used for single-breed and two-breed genomic
      predictions. The data included 5215 Nordic Holstein bulls and 4361 Nordic Red
      bulls, which was composed of three populations: Danish Red, Swedish Red and
      Finnish Ayrshire. The bulls were genotyped with 50 000 SNP chip. Using the two
      breed predictions with a joint Nordic Holstein and Nordic Red reference
      population, accuracies increased slightly for all traits in Nordic Red, but only
      for some traits in Nordic Holstein. Among the three subpopulations of Nordic Red,
      accuracies increased more for Danish Red than for Swedish Red and Finnish
      Ayrshire. This is because closer genetic relationships exist between Danish Red
      and Nordic Holstein. Among Danish Red, individuals with higher genomic
      relationship coefficients with Nordic Holstein showed more increased accuracies
      in the two-breed predictions. Weighting the two-breed G-matrices by LD phase
      consistencies, marker effects or both did not further improve accuracies of the
      two-breed predictions. 

PMID- 24750285
TI  - Bullous morphea arising at the site of a healed herpes zoster.

PMID- 24750284
TI  - A pilot study of the effects of the somatostatin analog pasireotide in
      postoperative dumping syndrome.
AB  - BACKGROUND: Dumping syndrome is characterized by distinct pathophysiological
      features such as postprandial increase in hematocrit (HT) and pulse rate (PR) and
      delayed hypoglycemia (HG). Treatment is based on dietary measures and
      somatostatin analogs (SA), but current SAs have incomplete efficacy, possibly
      through limited affinity for various somatostatin receptor subtypes. We evaluated
      the effect of pasireotide, a novel SA with high affinity for 4/5 human
      somatostatin receptors, on pathophysiological events and symptoms in dumping.
      METHODS: Randomized double-blind placebo-controlled cross-over study of nine
      patients (six women, 47 +/- 4 years) with postoperative dumping. Baseline
      measurements included oral glucose tolerance testing (OGTT), abdominal
      ultrasound, and dumping symptom severity score (DSSS). Patients were treated for
      2 weeks with placebo or pasireotide 300 MUg s.c. t.i.d. with a 1-week wash-out in
      a randomized fashion. On day 13 and 14 of each treatment OGTT, DSSS, and solid
      and liquid gastric emptying (GE) were obtained. KEY RESULTS: Baseline OGTT was
      pathological in all patients based on PR (n = 5), HT (n = 1) or HG (n = 7).
      Compared to placebo, pasireotide suppressed the increase in PR (17.1 +/- 2.8 vs
      8.2 +/- 3.5 bpm; p < 0.05) and late HG (nadir glycemia 55.6 +/- 4.3 vs 83.3 +/-
      9.5 mg/dL; p = 0.007), increased peak glycemia (294.1 +/- 33.3 vs 221.0 +/- 23.1
      mg/dL; p = 0.001) and delayed GE of solids (t1/2 83 +/- 23 vs 43 +/- 9 min; p =
      0.05) and liquids (t1/2 70 +/- 10 vs 40 +/- 4 min, p = 0.05). The differences in
      DSSS did not reach statistical significance. Two patients dropped out because of
      adverse gastrointestinal events under pasireotide. CONCLUSIONS & INFERENCES:
      Pasireotide affects pathophysiological features of both early and late dumping
      syndrome.

PMID- 24750286
TI  - A nurse-family partnership intervention to increase the self-efficacy of family
      caregivers and reduce catheter-associated urinary tract infection in catheterized
      patients.
AB  - The purpose of this study was to evaluate the effects of a nurse-family
      partnership model on the self-efficacy of family caregivers (FCs) and the
      incidence of catheter-associated urinary tract infection (CAUTI) among patients.
      A randomized controlled study was conducted. We recruited 61 patients and their
      FCs, who were randomly divided into an experimental group (n = 30) and a control
      group (n = 31). In the experimental group, the main caregivers comprised a nurse
      family partnership, whereas the control participants received routine care. The
      findings were as follows: (i) the incidence of CAUTI was lower in the
      experimental group than in the control group (20% vs. 38.8%), but the difference
      was not statistically significant; and (ii) no significant difference emerged for
      reported Caregiver Self-Efficacy Score between the two groups. The nursing team
      and FCs must become partners in cooperative caregiving to enhance the quality of
      patient care. 

PMID- 24750287
TI  - Carl Gustav Groth MD, PhD.

PMID- 24750289
TI  - Post-transplant malignancy: a burdensome complication in renal allograft
      recipients in Korea.
AB  - Cancer has been a serious complication of kidney transplantation ever since the
      outcome of this procedure improved. The incidence of cancer among kidney
      transplant (KT) recipients is increasing, and these patients have a higher risk
      of developing cancer than the general population. The present retrospective
      cohort study compared the cancer rate of kidney recipients in a single
      transplantation center in Korea with that in healthy Korean individuals using the
      standardized incidence ratio (SIR). The medical records of all 2365 patients who
      underwent renal transplantation between 1989 and 2009 were reviewed
      retrospectively. During the study period, 136 renal allograft recipients
      developed 140 malignancies. The cumulative cancer incidence one, five, 10, and 15
      yr post-transplantation was 0.60%, 3.24%, 5.69%, and 8.90%, respectively. Non
      Hodgkin lymphoma (NHL) and thyroid cancer were the most common cancers after
      renal transplantation, occurring significantly more frequently than in the
      general Korean population. The SIR of all cancers was 1.9 (women: 2.4; men: 1.6).
      Comparison with similar studies in Korea and other countries suggests transplant
      center-related differences dictate post-transplant malignancy incidence more
      strongly than ethnic or geographic factors. Early surveillance programs for de
      novo malignancies after kidney transplantation focusing on kidney-transplantation
      related tumors and postoperative time period should be established. 

PMID- 24750288
TI  - Predictors of post-traumatic psychological growth in the late years after lung
      transplantation.
AB  - BACKGROUND: Although lung transplantation improves quality of life, most
      psychosocial research focuses on adverse psychological and social functioning
      outcomes. Positive effects, particularly in the late-term years as physical
      morbidities increase, have received little attention. We provide the first data
      on a psychological benefit - post-traumatic growth (PTG) - and we focused on long
      term (>5 yr) survivors. METHODS: Among 178 patients from a prospective study of
      mental health during the first two yr post-transplant, we recontacted survivors 6
      11 yr post-transplant. We assessed PTG (i.e., positive psychological change
      resulting from the transplant) and examined its relationship to other patient
      characteristics with multivariable regression analyses. RESULTS: Sixty-four
      patients (86% of survivors) were assessed (M = 8.1 yr post-transplant, SD = 1.2).
      Mean PTG exceeded the scale's midpoint (M = 38.6, SD = 10.0; scale midpoint =
      25). Recipients experiencing greater PTG were female (p = 0.022), less educated
      (p = 0.014), and had a history of post-transplant panic disorder (p = 0.005),
      greater friend support (p = 0.048), and better perceived health (p = 0.032).
      Neither other pre- or post-transplant mood and anxiety disorders nor transplant
      related morbidities (acute rejection, bronchiolitis obliterans syndrome)
      predicted PTG. CONCLUSIONS: PTG exceeded levels observed in other chronic disease
      populations, suggesting that lung transplantation may uniquely foster positive
      psychological change in long-term survivors. PTG occurs despite physical and
      psychiatric morbidities. Whether PTG promotes other positive post-transplant
      psychosocial outcomes deserves attention.

PMID- 24750290
TI  - To induce or not to induce: a 21st century evaluation of lung transplant
      immunosuppression's effect on survival.
AB  - INTRODUCTION: The impact of induction immunosuppression on long-term survival in
      lung transplant recipients remains unclear. We sought to evaluate the effect of
      contemporary induction immunosuppression agents in lung transplant recipients'
      survival, utilizing national registry data. METHODS: We queried the United
      Network for Organ Sharing registry from 2001 to 2012 for adult, deceased donor
      lung transplants who received no antibody-based induction (NONE) or the
      contemporary agents of basiliximab, alemtuzumab, thymoglobulin, antilymphocyte
      globulin, or antithymocyte globulin (INDUCED). Kaplan-Meier estimates of the
      survival and Cox proportional hazards models assessed differences in overall
      survival between the INDUCED and NONE groups; logistic regression models assessed
      differences in survival and rejection (TR1Y). RESULTS: There were 23 951 lung
      transplants performed with 12 858 meeting the inclusion criteria; 5713 (44%) were
      INDUCED. Of INDUCED agents, 62% were basiliximab and 14% alemtuzumab. Being
      INDUCED significantly increased overall survival (p < 0.0001). Median INDUCED
      survival was 71.3 months (confidence interval [CI]: 65.7-75.5) as compared with
      63.2 months (CI: 60.1-65.9). Of INDUCED, both basiliximab and alemtuzumab had
      higher median survival times at 75.1 months (CI: 68.6-81.3) and 75.5 months (CI:
      63.5-infinity), respectively. There was less TR1Y in INDUCED patients (37%), as
      compared to NONE (42%; p < 0.0001). CONCLUSION: In a contemporary analysis of
      lung transplant recipients, induction immunosuppression has a significantly
      positive effect on survival.

PMID- 24750291
TI  - Active cytomegalovirus infection is not a risk factor for Epstein-Barr virus
      DNAemia in the allogeneic stem cell transplantation setting.

PMID- 24750292
TI  - Bortezomib induces thrombocytopenia by the inhibition of proplatelet formation of
      megakaryocytes.
AB  - Bortezomib is a potent proteasome inhibitor that has been extensively used to
      treat multiple myeloma. One of the most common grade 3 adverse events is cyclic
      thrombocytopenia. In this study, we studied the mechanism by which bortezomib
      induces thrombocytopenia in a mouse model. After the intravenous administration
      of bortezomib (2.5 mg/kg) via tail vein, platelet counts significantly decreased
      on days 2-4 and recovered to the normal range on day 6. Bortezomib (2.5 mg/kg)
      injected into mice in vivo did not affect colony-forming unit-megakaryocytes (CFU
      Mk) or megakaryocytes in the bone marrow. However, proplatelet formation (PPF)
      significantly decreased on days 2 and 4, after bortezomib administration to mice.
      Meanwhile, CFU-Mk formation and the ploidy distribution of cultured
      megakaryocytes in vitro were not affected by bortezomib used at concentrations of
      <= 1 ng/mL. The PPF of megakaryocytes in vitro significantly decreased with 0.1,
      1, 10, and 100 ng/mL bortezomib. Considering the bortezomib concentration in
      clinical studies, these data strongly suggest that decreased PPF activity induces
      thrombocytopenia. To elucidate the mechanism behind decreased PPF, Western blot
      was performed. Activated Rho expression increased after the incubation of murine
      platelets with bortezomib. Decreased PPF activity was eliminated by the addition
      of Y27632, a Rho kinase inhibitor, in vitro. Given that the Rho/Rho kinase
      pathway is a negative regulator of PPF, bortezomib increases activated Rho,
      inducing decreased PPF, which results in decreased platelet count.

PMID- 24750293
TI  - The influence of interimplant divergence on the retention characteristics of
      locator attachments, a laboratory study.
AB  - PURPOSE: The aim of the study was to assess the influence of interimplant
      divergence on retention of two Locator attachments before and after in vitro
      simulation of 3 to 5 years of use. MATERIALS AND METHODS: A hydraulic universal
      testing machine was used to measure the retention of two blue Locator attachments
      during 5500 seating and unseating cycles. Ten pairs of Locators were tested with
      interimplant divergences of 0 degrees , 10 degrees , and 20 degrees . Scanning
      electron microscopy (SEM) was used to examine surface changes of the components.
      The results were tested with ANOVA and Bonferroni post hoc correction when
      normally distributed. Results that were not normally distributed were tested with
      Kruskal-Wallis one-way ANOVA by ranks. RESULTS: At the start of the experiment
      the 10 degrees  group showed significantly more retention than the 0 degrees 
      group, but no significant difference was found between the 0 degrees  and 20
      degrees  groups or the 10 degrees  and 20 degrees  groups. After 5500 cycles,
      there was no significant difference in retention between any of the groups. The
      SEM images showed an approximately equal amount of wear in the nylon patrix
      inserts from all the groups. CONCLUSIONS: The retention of Locator pairs was not
      impaired by interimplant divergence of up to 20 degrees . Retention after 5500
      removal cycles was less than the initial retention in all groups. The nylon
      Locator patrices showed wear defects of similar location, type, and magnitude in
      the SEM images, regardless of interimplant angulation.

PMID- 24750295
TI  - Outcomes of allogeneic haemopoietic stem cell transplants at a small New Zealand
      centre: does size matter?
AB  - BACKGROUND: Reduced intensity conditioning (RIC) protocols for allogeneic
      haemopoietic cell transplants (HCT) have become commonplace treatments for
      patients with haematological disease, extending allogeneic HCT to older and less
      fit patients. There is a perception that centres treating larger numbers of
      patients have improved outcomes. AIMS: We wanted to examine whether outcomes for
      adult allogeneic HCT patients from our smaller centre were equivalent to those
      expected at larger centres internationally. METHODS: Clinical and laboratory data
      were collected on all patients who received allogeneic HCT during 2000-2012.
      Outcomes, including overall survival (OS) and progression-free survival, were
      compared between patients receiving myeloablative conditioning (MAC) and RIC
      protocols. RESULTS: One hundred and eighteen adult patients underwent allogeneic
      HCT with MAC (n = 51) or RIC (n = 67). The mean age of patients receiving MAC
      (35.8 years, range 18-56) was lower than those receiving RIC (48.4 years, range
      19-64). Two-year OS was similar for MAC and RIC patients (66% vs 62%, P = 0.17),
      whereas 2-year progression-free survival was superior in MAC patients (63% vs
      50%, P = 0.01) due to fewer relapses. OS was reduced in older patients
      irrespective of conditioning. Patients with chronic graft-versus-host disease had
      improved survival due to fewer relapses. OS was unaffected by HCT comorbidity
      index, donor, cell source or patient/donor cytomegalovirus status. CONCLUSION:
      RIC protocols have resulted in long-term survival in many patients ineligible for
      MAC protocols. In our smaller centre, patient age but not conditioning intensity
      influenced survival, which was equivalent to reports from larger centres.

PMID- 24750294
TI  - The relationship of the lipoprotein SsaB, manganese and superoxide dismutase in
      Streptococcus sanguinis virulence for endocarditis.
AB  - Streptococcus sanguinis colonizes teeth and is an important cause of infective
      endocarditis. Our prior work showed that the lipoprotein SsaB is critical for S.
      sanguinis virulence for endocarditis and belongs to the LraI family of conserved
      metal transporters. In this study, we demonstrated that an ssaB mutant
      accumulates less manganese and iron than its parent. A mutant lacking the
      manganese-dependent superoxide dismutase, SodA, was significantly less virulent
      than wild-type in a rabbit model of endocarditis, but significantly more virulent
      than the ssaB mutant. Neither the ssaB nor the sodA mutation affected sensitivity
      to phagocytic killing or efficiency of heart valve colonization. Animal virulence
      results for all strains could be reproduced by growing bacteria in serum under
      physiological levels of O(2). SodA activity was reduced, but not eliminated in
      the ssaB mutant in serum and in rabbits. Growth of the ssaB mutant in serum was
      restored upon addition of Mn(2+) or removal of O(2). Antioxidant supplementation
      experiments suggested that superoxide and hydroxyl radicals were together
      responsible for the ssaB mutant's growth defect. We conclude that manganese
      accumulation mediated by the SsaB transport system imparts virulence by enabling
      cell growth in oxygen through SodA-dependent and independent mechanisms.

PMID- 24750296
TI  - Association of antibodies to ganglioside complexes and conduction blocks in
      axonal Guillain-Barre syndrome presenting as acute motor conduction block
      neuropathy.
AB  - A close relationship between acute motor conduction block neuropathy and
      antibodies against the complex of GM1 and GalNAc-GD1a has been reported. This
      study investigates the hypothesis that conduction block at the early phase of
      axonal Guillain-Barre syndrome (GBS) is also associated with such ganglioside
      complexes. Sera were obtained from seven French patients with initial evidence of
      isolated conduction blocks that resolved or progressed to acute motor axonal
      neuropathy. Serum IgG to asialo-GM1 and gangliosides of LM1, GM1, GM1b, GD1a,
      GalNAc-GD1a, GD1b, GT1a, GT1b, and GQ1b as well as their complexes were measured.
      Five of seven patients progressed within the first month of disease to AMAN. One
      patient had IgG antibodies against the complex of asialo-GM1 and each of the
      other ganglioside antigens. Another patient carried IgG antibodies against GM1
      complex with GM1b, GD1a, and GT1a as well as asialo-GM1 complex with GD1a and
      GT1a. None had IgG antibodies against GM1/GalNAc-GD1a complex. Six patients had
      IgG against single antigens GM1, GD1a, GalNAc-GD1a, GD1b, and asialo-GM1. In
      three patients, a reduced reaction against GM1/GalNAc-GD1a complex was observed.
      The presence of conduction block in axonal GBS is not always associated with anti
      GM1/GalNAc-GD1a complex antibodies. 

PMID- 24750297
TI  - Performance of Enhanced Liver Fibrosis test and comparison with transient
      elastography in the identification of liver fibrosis in patients with chronic
      hepatitis B infection.
AB  - Assessment of liver fibrosis is important in determining prognosis, disease
      progression and need for treatment in patients with chronic hepatitis B (CHB).
      Limitations to the use of liver biopsy in assessing fibrosis are well recognized,
      and noninvasive tests are being increasingly evaluated including transient
      elastography (TE) and serum markers such as the Enhanced Liver Fibrosis (ELF)
      test. We assessed performance of ELF and TE in detecting liver fibrosis with
      reference to liver histology in a cohort of patients with CHB (n = 182), and
      compared the performance of these modalities. Median age was 46 and mean AST 70
      IU/L. Cirrhosis was reported in 20% of liver biopsies. Both modalities performed
      well in assessing fibrosis at all stages. Area under receiver operator
      characteristic (AUROC) curves for detecting METAVIR fibrosis stages F >= 1, F >=
      2, F >= 3 and F4 were 0.77, 0.82, 0.80 and 0.83 for ELF and 0.86, 0.86, 0.90 and
      0.95 for TE. TE performed significantly better in the assessment of severe
      fibrosis (AUROC 0.80 for ELF and 0.90 for TE, P < 0.01) and cirrhosis (0.83 for
      ELF and 0.95 for TE, P < 0.01). This study demonstrates that ELF has good
      performance in detection of liver fibrosis in patients with CHB, and when
      compared, TE performs better in detection of severe fibrosis/cirrhosis.

PMID- 24750298
TI  - Metastatic retinoblastoma of mandible diagnosed on fine needle aspiration
      cytology.

PMID- 24750299
TI  - A topographic anatomical study of the equine epiploic foramen and comparison with
      laparoscopic visualisation.
AB  - REASONS FOR PERFORMING STUDY: There are no previous studies correlating the
      anatomy of the equine epiploic foramen and its defining structures with
      laparoscopic images. OBJECTIVES: The purpose of this study was to describe the
      precise anatomy of the epiploic foramen and omental vestibule, to quantify the
      dimensions of the epiploic foramen and to relate these findings to laparoscopic
      images. STUDY DESIGN: Descriptive study of cadaver material and laparoscopic
      images. METHODS: Thirty-two horses subjected to euthanasia for reasons unrelated
      to colic were studied. Two cadavers were used to make vascular casts of the
      coeliac artery and portal vein. In 30 cadavers the epiploic foramen and omental
      vestibule were cast with a polyurethane prepolymer immediately after euthanasia.
      The cast served as a landmark during dissection and the circumference of the
      epiploic foramen was measured from these casts. Histology was performed on
      structures defining the epiploic foramen in 2 horses. Laparoscopic images from 6
      standing right flank procedures were reviewed. RESULTS: The defining structures
      of the epiploic foramen and omental vestibule are the hepatoduodenal ligament,
      hepatogastric ligament and the gastropancreatic and hepatopancreatic folds. The
      hepatoduodenal ligament has a secondary fold which forms the ventral border of
      the epiploic foramen, consisting of a central connective tissue core of mainly
      elastin fibres. The hepatic artery for part of its course is incorporated in the
      hepatoduodenal ligament. All these structures are clearly visible
      laparoscopically. The mean circumference of the epiploic foramen is 11.6 +/- 2.6
      cm and its circumference is positively correlated with body weight but is
      unrelated to age or gender. CONCLUSIONS: Several clinically relevant structures
      delineate the epiploic foramen. Its defining structure consists, in part, of
      elastin fibres. Anatomical and laparoscopic knowledge may assist surgeons in
      developing interventions to treat diseases involving the epiploic foramen.

PMID- 24750300
TI  - Acute prostatitis caused by Raoultella planticola in a renal transplant
      recipient: a novel case.
AB  - We present a unique case of acute bacterial prostatitis caused by a very rare
      human pathogen, Raoultella planticola, in a renal allograft recipient 3.5 months
      post transplantation. Only a few cases of human infection by this pathogen have
      been reported worldwide. The present study reports the case of a 67-year-old man
      who was admitted to our transplant unit 3.5 months post transplantation with
      fever, dysuria, suprapubic pain, symptoms and signs of acute prostatitis, and
      elevated markers of inflammation and prostate-specific antigen. R. planticola was
      isolated in the urine culture. The patient was treated with ciprofloxacin (based
      on the antibiogram) and had a full recovery, with satisfactory renal function. To
      the best of our knowledge, this is not only the first reported case of R.
      planticola prostatitis, but also the first report of such an infection in a solid
      organ transplant recipient or in a patient on immunosuppressive medication.

PMID- 24750302
TI  - Constraints imposed by pollinator behaviour on the ecology and evolution of plant
      mating systems.
AB  - Most flowering plants rely on pollinators for their reproduction. Plant
      pollinator interactions, although mutualistic, involve an inherent conflict of
      interest between both partners and may constrain plant mating systems at multiple
      levels: the immediate ecological plant selfing rates, their distribution in and
      contribution to pollination networks, and their evolution. Here, we review
      experimental evidence that pollinator behaviour influences plant selfing rates in
      pairs of interacting species, and that plants can modify pollinator behaviour
      through plastic and evolutionary changes in floral traits. We also examine how
      theoretical studies include pollinators, implicitly or explicitly, to investigate
      the role of their foraging behaviour in plant mating system evolution. In doing
      so, we call for more evolutionary models combining ecological and genetic
      factors, and additional experimental data, particularly to describe pollinator
      foraging behaviour. Finally, we show that recent developments in ecological
      network theory help clarify the impact of community-level interactions on plant
      selfing rates and their evolution and suggest new research avenues to expand the
      study of mating systems of animal-pollinated plant species to the level of the
      plant-pollinator networks. 

PMID- 24750301
TI  - Transcutaneous electrical nerve stimulation for the relief of post-partum uterine
      contraction pain during breast-feeding: a randomized clinical trial.
AB  - AIM: To evaluate transcutaneous electrical nerve stimulation (TENS) used to
      relieve uterine contraction pain during breast-feeding in multiparous women.
      METHODS: A controlled and randomized clinical trial was performed with 32 post
      partum multiparous women who were breast-feeding. The participants were
      randomized into an experimental (EG, n = 16) and a control group (CG, n = 16).
      Pain was assessed using the Numerical Rating Scale and the descriptors of the
      Present Pain Intensity (PPI - McGill) during two sequential feeds. In the first
      assessment, the post-partum women in the EG and CG were monitored while breast
      feeding and questioned regarding the degree of uterine contraction pain. In the
      second assessment, which was performed at the next feed, the EG used TENS while
      the CG was monitored, with pain being reassessed following. In the EG, the TENS
      electrodes were placed between T10-L1 and S2-S4, with a frequency of 100 Hz, a
      pulse duration of 75 MUs and amplitude adjusted to produce a strong and tolerable
      sensation for 40 min. A descriptive analysis of the data and comparative intra-
      and intergroup analyses were performed by means of a non-parametrical test, with
      a significance level P <= 0.05. RESULTS: The level of basal pain was 5.56 in the
      EG and 5.50 in the CG. In the intragroup analysis, the EG (P < 0.0001) and CG (P
      = 0.04) presented significant pain reduction. In the intergroup analysis, the EG
      had significant pain reduction (P < 0.01) in comparison to the CG. In the PPI
      analysis, a non-significant decrease in pain intensity was observed in the EG.
      CONCLUSION: TENS was found to be effective in reducing post-partum uterine
      contraction pain during breast-feeding.

PMID- 24750303
TI  - Role of obesity on the thickness of primary cutaneous melanoma.
AB  - BACKGROUND: Thick primary cutaneous melanoma (PCM) is associated with older age,
      male sex, being single, a low educational level, self-detection and general
      practice detection, nodular melanoma (NM) and acral lentiginous melanoma (ALM)
      types; and are found in the head-neck and lower limb locations. Obesity plays a
      direct role on melanoma tumour growth, as it has been shown in animal models, but
      its role in the thickness of PCM remains unknown. OBJECTIVES: We investigated the
      impact of obesity on the thickness of invasive PCM. METHODS: A cross-sectional
      study was performed in a prospective cohort for which we collected several
      clinical and histological data already known to be associated with thick PCM and
      the Body Mass Index from new cases of invasive PCM which were referred to the
      dermatology department in Valence. RESULTS: Four hundred and twenty-seven
      patients were studied. In an univariate analysis, thick PCM was associated with
      low educational level, obesity, identification by the patient or the general
      practitioner (GP), location on the cephalic extremity, in a non-visible area of
      the body, the NM and ALM type, and an ulceration. In a multivariate analysis, NM,
      ulceration, topography of the melanoma and identification of the melanoma by the
      patient or GP were significantly associated with thick melanoma. When including
      only clinical features in the model, low educational level, mode of melanoma
      identification and obesity were significantly associated with a risk of thick
      melanoma. CONCLUSIONS: Obesity is a clinical independent risk factor of thick
      PCM. For health policies, governments should pay greater attention to detect
      melanoma in obese patients. Our results encourage the basic research on tumoural
      growth mechanisms due to obesity in melanoma.

PMID- 24750304
TI  - Drugs acting at 5-HT4 , D2 , motilin, and ghrelin receptors differ markedly in
      how they affect neuromuscular functions in human isolated stomach.
AB  - BACKGROUND: Progress in identifying safer, effective drugs to increase gastric
      emptying is impeded by failed clinical trials. One potential reason for failure
      is lack of translation from animal models to the human condition. To make
      progress, the actions of existing drugs and new therapeutic candidates need to be
      understood in human isolated stomach. METHODS: Neuromuscular activities were
      evoked in human gastric antrum circular muscle by electrical field stimulation
      (EFS), defined phenotypically using pharmacological tools. KEY RESULTS: EFS
      evoked cholinergically mediated contractions, attenuated by simultaneous
      nitrergic activation. The 5-HT4 receptor agonist/D2 antagonist metoclopramide and
      the selective 5-HT4 agonist prucalopride, facilitated contractions in the absence
      (respectively, Emax 95 +/- 29% and 42 +/- 9%, n = 3-6 each concentration) and
      presence (139 +/- 38%, 55 +/- 13%, n = 3-5) of the NO synthase inhibitor L-NAME,
      without affecting submaximal contractions to carbachol; the 5-HT4 antagonist
      SB204070 prevented facilitation by metoclopramide 100 MUM (respectively, -5
      (range -26 to 34) and 167 (12-1327)% in presence and absence; n = 5-6). The
      selective motilin receptor agonist camicinal provided considerably greater
      facilitation (478 (12-2080)% at 30 MUM, n = 8). Domperidone (0.001-100 MUM; n = 3
      6) and acylated or des-acylated ghrelin (1-300 nM; n = 2-4) had no consistent
      activity, even with protease inhibitors. CONCLUSIONS & INFERENCES: 5-HT4 receptor
      agonists show different efficacies. Motilin receptor activation has greater
      potential to increase gastric emptying, whereas ghrelin and D2 receptor
      antagonism have no direct activity. Drugs stimulating human gastric motility
      directly can act regardless of disease mechanisms, whereas drugs without direct
      activity but an ability to block nausea/vomiting may be effective only if these
      symptoms exist.

PMID- 24750305
TI  - 125 Cases of duodenoduodenostomy in pancreas transplantation: a single-centre
      experience of an alternative enteric drainage.
AB  - Several exocrine drainage procedures have been successfully developed to perform
      pancreas transplantation (PT). Retroperitoneal graft placement allows exocrine
      drainage via direct duodenoduodenostomy (DD). This technique provides easy access
      for endoscopic surveillance and biopsy. A total of 241 PT procedures were
      performed in our centre between 2002 and 2012. DD was performed in 125 patients,
      and duodenojejunostomy (DJ) in 116 patients. We retrospectively compared our
      experience with these two types of enteric drainage, focusing on graft and
      patient survivals, as well as postoperative complications. With a mean follow-up
      of 59 months, both groups demonstrated comparable patient and graft survivals. 14
      (11%) of 125 cases in the DD group and 21 (18%) of 116 cases in the DJ group had
      pancreatic graft loss (P = 0.142). Graft thrombosis [5 (4%) vs. 18 (16%) P =
      0.002], anastomotic insufficiency [2 (1.6%) vs. 8 (7%) P = 0.052] and
      relaparotomy [52 (41%) vs. 56 (48%) P = 0.29] occurred more frequently in the DJ
      group, whereas gastrointestinal bleeding [14 (11%) vs. 4 (3%) P = 0.026] occurred
      more often in the DD group. DD is a feasible and safe technique in PT, with no
      increase in enteric complications. It is equivalent to other established
      techniques and extends the feasibility of anastomotic sites, especially in
      recipients who have undergone a second transplantation. 

PMID- 24750306
TI  - Esthetic outcome and alterations of soft tissue around single implant crowns: a 2
      year prospective study.
AB  - OBJECTIVE: The aim of this prospective study was to assess the esthetic outcome
      and alterations of peri-implant soft tissue using tissue-level implants.
      Furthermore, the influencing factors, including grafting and gingival biotype, of
      esthetic outcome of peri-implant soft tissue were also evaluated. MATERIALS AND
      METHODS: Of 38 patients with single missing anterior tooth in maxilla were
      treated with a Straumann ((r)) Standard Plus SLA implant. Bone augmentation was
      performed in 24 patients. Follow-up was conducted at 12 and 24 months after
      definitive crowns placement. Esthetic outcome using the pink esthetic score/white
      esthetic score (PES/WES) and clinical parameters were evaluated. RESULTS: The
      mean PES/WES value at baseline, 1-year, and 2-year examination was 13.79, 14.87,
      and 14.96. Significant improvement was found between baseline and 1-year
      examination (P < 0.01). And the improvement between 1-year and 2-year examination
      was not significant (P = 0.40). The mean PES changing value in patients with
      thick biotype was significantly higher than those with thin biotype at 2-year
      after definitive crowns placement (P = 0.03). Graft procedure had an unfavorable
      effect on mean PES value both at baseline and at follow-up (P < 0.01). No
      implants were lost at 2-year examination. Three patients experienced peri-implant
      infection. No significant difference was found with the passage of time in
      modified plaque index (mPI), probing pocket depth (PPD), and modified bleeding
      index (mBI). CONCLUSION: According to the present prospective clinical study, it
      can be concluded that it is feasible to use tissue-level implant to support
      single crowns in esthetic area. Favorable short-term esthetic outcome and
      stability of soft tissue around single implant crowns can be expected in patients
      with or without graft. However, graft procedures might have an unfavorable effect
      on the esthetic outcome. Gingival biotype can be considered as prognostic factor
      for esthetic outcome. RCTs with long-term follow-up are needed to provide
      evidence for the long-term stability of peri-implant soft tissue using tissue
      level implant systems.

PMID- 24750307
TI  - Philadelphia chromosome-positive mixed phenotype acute leukemia in the imatinib
      era.
AB  - Although the introduction of imatinib dramatically improved the outcomes for
      patients with Philadelphia chromosome-positive B-cell precursor acute
      lymphoblastic leukemia (Ph + BCP-ALL), the survival benefit of imatinib has not
      been assessed in the context of Ph + mixed phenotype acute leukemia (Ph + MPAL).
      To clarify this important issue, we studied 42 Ph+ acute leukemia (Ph + AL)
      patients who received intensive chemotherapy and concurrent administration of
      imatinib. Of the 42 Ph + AL patients, 13 (31%) patients were categorized as Ph +
      MPAL (positive for both myeloid and B-cell lineage), 27 (64%) were categorized as
      Ph + BCP-ALL, and two (5%) were categorized as Ph + acute myeloid leukemia. The
      complete remission rates after the initial induction therapy were not
      significantly different when comparing Ph + MPAL and Ph + BCP-ALL patients (100%
      vs. 85%, respectively, P = 0.14). Likewise, there were no significant differences
      in the 5-yr overall survival (OS) or disease-free survival (DFS) rates when
      comparing the MPAL and BCP-ALL groups (OS: 55% vs. 53%, respectively, P = 0.87,
      DFS: 46% vs. 42%, respectively, P = 0.94). These findings suggest that concurrent
      imatinib administration with chemotherapy improved the outcomes of Ph + MPAL
      patients to the level seen in Ph+BCP-ALL patients and should, therefore, be
      considered as the standard therapy for these patients.

PMID- 24750308
TI  - Resilience in families of children with Down syndrome in Korea.
AB  - This study aims to identify the factors related to resilience of the families of
      children with Down syndrome (DS). Data were collected from 126 parents of
      children with DS in Korea, using a self-administered questionnaire. The age of
      the child, developmental level of the child, parental depression, and stress and
      strain were negatively related with family adaptation, whereas health of parents,
      family cohesiveness, flexibility, communication skills, supportive
      family/relatives, and quality of community service were positively related.
      Parental depression, family cohesiveness and communication skills were the
      factors that were strongly related to family resilience and adaptation. It is
      suggested that nursing interventions to decrease parental depression and increase
      family cohesiveness and communication skills should be included to increase
      resilience of the families of children with DS. 

PMID- 24750309
TI  - Generic tacrolimus in solid organ transplantation.
AB  - The availability of a wide range of immunosuppressive therapies has
      revolutionized the management of patients who have undergone solid organ
      transplantation (SOT). However, the cost of immunosuppressive drugs remains high.
      This situation has led to the development of generic equivalents, which are
      similar in quality, safety, and efficacy to their approved innovator drugs. There
      are data available for three generic brands, tacrolimus (Intas), tacrolimus
      (PharOS), and tacrolimus (Sandoz). Bioequivalence has been demonstrated for
      generic tacrolimus (Sandoz) within a narrow therapeutic range to its innovator
      tacrolimus drug (Prograf) in both healthy volunteers and kidney transplant
      patients. Clinical experience with this generic tacrolimus formulation has also
      been established in both de novo and conversion patients who have undergone
      kidney and liver transplantation, as well as in conversion of other SOT patients,
      including lung and heart recipients. 

PMID- 24750310
TI  - Risk indicators for root caries in institutionalized elders.
AB  - OBJECTIVE: To investigate the risk indicators for root caries in
      institutionalized elders. METHODS: Nonfrail elders living in 21 residential
      elderly homes who had at least 5 teeth with exposed roots were examined in this
      cross-sectional study. The dental examinations were conducted by one trained
      dentist in the elderly homes using a portable clinic light, mouth mirror, and
      dental explorer. Two-level logistic regression analyses, one using the presence
      of decay and the other using decay/filling in the root surface as the dependent
      variable, were conducted to study the relationship between root caries and a
      number of selected subject-level and site-level factors. RESULTS: A total of 306
      elders with a mean age of 78.8 years were examined. Their mean DS-root and DFS
      root scores were 1.3 and 2.1, respectively. Their mean root caries index score
      was 3.92. Results from the regression analyses revealed a positive correlation
      between the caries status of the root surfaces in the same subject (ICC1 =0.37,
      ICC2 =0.29, P < 0.001). Root surfaces with visual plaque, with denture contact,
      with more gingival recession, and in the upper anterior region were found to have
      a higher chance of being affected by root caries. CONCLUSION: Presence of plaque,
      proximity to denture, and gingival recession are important site-level risk
      indicators for root caries in institutionalized elders. More attention should be
      paid to plaque control on exposed root surfaces and avoiding placement of denture
      components close to roots so as to lower the risk of root caries in elders.

PMID- 24750311
TI  - Improvement in dental porcelain bonding to milled, noncast titanium surfaces by
      gold sputter coating.
AB  - PURPOSE: This study evaluated the adherence of dental porcelain to a milled,
      noncast titanium (Ti) surface with a gold sputter coating to evaluate a possible
      new practical surface treatment for enhancing the bond strength between Ti and
      porcelain. MATERIALS AND METHODS: Milled, noncast Ti strips were created by
      computer-aided design and manufacturing processes. The milled, noncast Ti strips
      were sandblasted with alumina particles and were then sequentially subjected to
      gold sputter coating treatments of 150- and 300-second duration. Low-fusion
      dental porcelain was then sintered onto the surface-treated Ti strips. The bond
      strengths of the Ti/porcelain specimens were evaluated using a three-point
      bending test (ISO 9693). Surface characterizations of the specimens were carried
      out with X-ray photoelectron spectrometry, scanning electron microscopy, and
      energy dispersive X-ray spectroscopy. RESULTS: The results indicated that the
      bond strengths of all the Ti/porcelain groups were greater than the minimum
      requirement (25 MPa) as prescribed by ISO 9693. The gold sputter coating
      increased the oxidation resistance (or decreased the oxide content) of the Ti
      surface during porcelain sintering, which positively affected the bond strength
      of Ti/porcelain (approximately 36 MPa) compared to the untreated Ti/porcelain
      specimen (approximately 29 MPa). The fracture morphologies of all the
      Ti/porcelain groups revealed an adhesive bond failure as the interfacial fracture
      mode between the Ti and the porcelain. CONCLUSIONS: A practical and simple
      sandblasting/gold sputter coating treatment of Ti surfaces prior to porcelain
      sintering significantly strengthens the bond between the milled, noncast Ti and
      the dental porcelain.

PMID- 24750312
TI  - Hereditary haemorrhagic telangiectasia, an Australian cohort: clinical and
      investigative features.
AB  - AIM: The present study aims to describe the phenotypic features of patients with
      hereditary haemorrhagic telangiectasia (HHT) seen at Royal Melbourne Hospital,
      Victoria, Australia, and to customise a protocol for surveillance of patients
      with HHT. METHODS: This is a retrospective study in a tertiary referral hospital
      of all patients referred to the Clinical Genetics Service between 2007 and 2011
      with a suspected diagnosis of HHT. Data abstracted from patient clinical records
      were analysed for clinical features, types of HHT and genetic testing results
      where available. RESULTS: Our cohort comprising 40 females and 23 males patients
      was assessed using the Curacao criteria. Twenty-two patients fulfilled the
      criteria for a definite diagnosis, 30 had a possible diagnosis, and 11 patients
      were assessed as unlikely to have HHT at the time of data analysis. Seventeen
      patients had pulmonary arteriovenous malformations (AVM), five had cerebral AVM,
      five had hepatic AVM, three had confirmed bowel telangiectasia, and one patient
      had a pancreatic AVM. Two female patients with HHT had complicated pregnancies
      during their follow up with us. Three families had mutations in the endoglin (ENG
      gene), three had mutations in the ACVRL1 gene, and two families had mutations in
      the SMAD4 gene. CONCLUSION: HHT is a multisystemic disorder and needs involvement
      of a team with experience in managing patients with HHT.

PMID- 24750313
TI  - HLA-DRB1* alleles genotyping in chronic inflammatory demyelinating polyneuropathy
      in Greek patients.

PMID- 24750314
TI  - Calcitriol inhibits keratinocyte proliferation by upregulating leukocyte elastase
      inhibitor (serpin B1).
AB  - Calcitriol had been proved to be effective for treatment of psoriasis vulgaris.
      However, the molecular events leading to the normalization of keratinocyte
      differentiation had not been fully explored. The aim of the study was to evaluate
      the role of calcitriol and serpin B1 in human keratinocyte cell line (HaCaT)
      proliferation. Proteins extracted from calcitriol-treated and untreated HaCaT
      were separated by 2-D differential gel electrophoresis (2DE). Then, the 2DE
      profiles were analyzed to screen for differentially expressed proteins, which
      were identified by matrix-assisted laser desorption/ionization time of flight
      mass spectrometry. The upregulation of serpin B1 was confirmed by quantitative
      reverse transcription polymerase chain reaction (qRT-PCR) and western blot
      analysis. The effect of serpin B1 on HaCaT proliferation was analyzed by RNA
      interference experiments, methylthiazoletetrazolium assay and flow cytometry.
      Reproducible 2-DE profiles of HaCaT were established. The result that serpin B1
      was upregulated in the calcitriol-treated group was confirmed by qRT-PCR and
      western blot analysis. Calcitriol could inhibit proliferation of HaCaT at the
      concentration of 10(-9) -10(-6 ) mol/L. HaCaT proliferation was promoted when
      serpin B1 was interfered. The inhibition effect of calcitriol was stopped after
      serpin B1 was interfered. Serpin B1 was overexpressed in calcitriol-treated HaCaT
      cells and may play an important role in inhibiting HaCaT proliferation by
      calcitriol. 

PMID- 24750315
TI  - Darwin's finches and their diet niches: the sympatric coexistence of imperfect
      generalists.
AB  - Adaptive radiation can be strongly influenced by interspecific competition for
      resources, which can lead to diverse outcomes ranging from competitive exclusion
      to character displacement. In each case, sympatric species are expected to evolve
      into distinct ecological niches, such as different food types, yet this
      expectation is not always met when such species are examined in nature. The most
      common hypotheses to account for the coexistence of species with substantial diet
      overlap rest on temporal variation in niches (often diets). Yet spatial variation
      in niche overlap might also be important, pointing to the need for spatiotemporal
      analyses of diet and diet overlap between closely related species persisting in
      sympatry. We here perform such an analysis by characterizing the diets of, and
      diet overlap among, four sympatric Darwin's ground finch species at three sites
      and over 5 years on a single Galapagos island (Santa Cruz). We find that the
      different species have broadly similar and overlapping diets - they are to some
      extent generalists and opportunists - yet we also find that each species retains
      some 'private' resources for which their morphologies are best suited.
      Importantly, use of these private resources increased considerably, and diet
      overlap decreased accordingly, when the availability of preferred shared foods,
      such as arthropods, was reduced during drought conditions. Spatial variation in
      food resources was also important. These results together suggest that the ground
      finches are 'imperfect generalists' that use overlapping resources under benign
      conditions (in space or time), but then retreat to resources for which they are
      best adapted during periods of food limitation. These conditions likely promote
      local and regional coexistence.

PMID- 24750317
TI  - Genome-wide scans detect adaptation to aridity in a widespread forest tree
      species.
AB  - Patterns of adaptive variation within plant species are best studied through
      common garden experiments, but these are costly and time-consuming, especially
      for trees that have long generation times. We explored whether genome-wide
      scanning technology combined with outlier marker detection could be used to
      detect adaptation to climate and provide an alternative to common garden
      experiments. As a case study, we sampled nine provenances of the widespread
      forest tree species, Eucalyptus tricarpa, across an aridity gradient in
      southeastern Australia. Using a Bayesian analysis, we identified a suite of 94
      putatively adaptive (outlying) sequence-tagged markers across the genome.
      Population-level allele frequencies of these outlier markers were strongly
      correlated with temperature and moisture availability at the site of origin, and
      with population differences in functional traits measured in two common gardens.
      Using the output from a canonical analysis of principal coordinates, we devised a
      metric that provides a holistic measure of genomic adaptation to aridity that
      could be used to guide assisted migration or genetic augmentation. 

PMID- 24750318
TI  - Standardizing corneal nerve fibre length for nerve tortuosity increases its
      association with measures of diabetic neuropathy.
AB  - AIMS: Recent studies on corneal markers have advocated corneal nerve fibre length
      as the most important measure of diabetic peripheral neuropathy. The aim of this
      study was to determine if standardizing corneal nerve fibre length for tortuosity
      increases its association with other measures of diabetic peripheral neuropathy.
      METHODS: Two hundred and thirty-one individuals with diabetes with either
      predominantly mild or absent neuropathic changes and 61 control subjects
      underwent evaluation of diabetic neuropathy symptom score, neuropathy disability
      score, testing with 10-g monofilament, quantitative sensory testing (warm, cold,
      vibration detection) and nerve conduction studies. Corneal nerve fibre length and
      corneal nerve fibre tortuosity were measured using corneal confocal microscopy. A
      tortuosity-standardised corneal nerve fibre length variable was generated by
      dividing corneal nerve fibre length by corneal nerve fibre tortuosity.
      Differences in corneal nerve morphology between individuals with and without
      diabetic peripheral neuropathy and control subjects were determined and
      associations were estimated between corneal morphology and established tests of,
      and risk factors for, diabetic peripheral neuropathy. RESULTS: The tortuosity
      standardised corneal nerve fibre length variable was better than corneal nerve
      fibre length in demonstrating differences between individuals with diabetes, with
      and without neuropathy (tortuosity-standardised corneal nerve fibre length
      variable: 70.5 +/- 27.3 vs. 84.9 +/- 28.7, P < 0.001, receiver operating
      characteristic area under the curve = 0.67; corneal nerve fibre length: 15.9 +/-
      6.9 vs. 18.4 +/- 6.2 mm/mm2, P = 0.004, receiver operating characteristic area
      under the curve = 0.64). Furthermore, the tortuosity-standardised corneal nerve
      fibre length variable demonstrated a significant difference between the control
      subjects and individuals with diabetes, without neuropathy, while corneal nerve
      fibre length did not (tortuosity-standardised corneal nerve fibre length
      variable: 94.3 +/- 27.1 vs. 84.9 +/- 28.7, P = 0.028; corneal nerve fibre length:
      20.1 +/- 6.3 vs. 18.4 +/- 6.2 mm/mm2, P = 0.084). Correlations between corneal
      nerve fibre length and established measures of neuropathy and risk factors for
      neuropathy were higher when a correction was made for the nerve tortuosity.
      CONCLUSIONS: Standardizing corneal nerve fibre length for tortuosity enhances the
      ability to differentiate individuals with diabetes, with and without neuropathy.

PMID- 24750316
TI  - Use of laser capture microdissection for the assessment of equine lamellar basal
      epithelial cell signalling in the early stages of laminitis.
AB  - REASONS FOR PERFORMING STUDY: Dysadhesion of laminar basal epithelial cells
      (LBECs) from the underlying dermis is the central event leading to structural
      failure in equine laminitis. Although many studies of sepsis-related laminitis
      have reported multiple events occurring throughout the lamellar tissue, there is
      minimal information regarding signalling events occurring specifically in LBECs.
      OBJECTIVES: To determine signalling events in the LBECs during the early stages
      of carbohydrate-induced laminitis. STUDY DESIGN: Experimental study. METHODS:
      Eight horses were given an overload of carbohydrate (CHO) consisting of corn
      starch mixture via nasogastric tube. Prior to administration of CHO, lamellar
      biopsies were taken from the left forefoot (control [CON]). Biopsies were taken
      from the left hind foot at the onset of fever (developmental [DEV]) and from the
      right forefoot at the onset of Obel grade 1 lameness (OG1). Laminar basal
      epithelial cells were isolated from cryosections using a laser capture
      microdissection (LCM) microscope. Next generation sequencing (RNA-seq) was used
      to identify transcripts expressed in the LBECs for each time point and
      bioinformatic analysis was performed with thresholds for between group
      comparisons set at a greater than 2-fold change and P value <=0.05. RESULTS:
      Forty genes (22 increased/18 decreased) were significantly different from DEV
      time vs. CON and 107 genes (57 increased/50 decreased) were significantly
      different from OG1 time vs. CON. Significant increases in inflammatory genes were
      present in addition to significantly altered expression of genes related to
      extracellular matrix composition, stability and turnover. CONCLUSIONS: Signalling
      related to inflammatory response and extracellular matrix regulation was strongly
      represented at the DEV and OG1 times. These results indicate that the LBEC is not
      only a casualty but also an active participant in lamellar events leading to
      structural failure of the digital lamellae in equine laminitis.

PMID- 24750319
TI  - Epicardial adipose tissue and coronary artery calcification in psoriasis
      patients.
AB  - BACKGROUND: Psoriasis is a chronic, immune-mediated disease associated with
      several cardio-metabolic comorbidities, accelerated atherosclerosis and
      cardiovascular disease (CVD). Other causes beyond systemic inflammation and
      traditional cardiovascular risk factors (CVRF) may be implicated in the increased
      risk of CVD observed in these patients. Epicardial adipose tissue (EAT), a type
      of visceral adipose tissue surrounding the heart and coronary vessels has been
      implicated in the development of coronary artery disease, by endocrine
      mechanisms, but particularly by local inflammation. OBJECTIVE: To compare EAT
      volumes in psoriasis patients and controls using multidetector computed
      tomography (MDCT) and to analyse if eventual differences were independent from
      abdominal visceral adiposity; to determine, within psoriasis patients, its
      relation with subclinical atherosclerosis and other markers of cardiometabolic
      risk. METHODS: One hundred patients with severe psoriasis, without CVD underwent
      MDCT, with EAT and abdominal visceral fat (AVF) assessment and coronary artery
      calcification (CAC) quantification and were compared with 202 control patients.
      RESULTS: EAT volume was increased in psoriasis patients compared to control
      subjects, independently from age, sex and AVF, being, on average, 15.2 +/- 4.41
      mL higher (95% CI: 6.5-26.0, P = 0.001) than in controls. Moreover, psoriasis
      patients had a statistically significant higher risk of having subclinical
      atherosclerosis (OR 2.52, 95% CI: 1.23-5.16) than controls, after adjusting for
      traditional CVRF. Within psoriasis patients EAT volume was associated with
      subclinical atherosclerosis, independently of age, sex, psoriasis duration,
      classical CVRF and AVF. CONCLUSION: This study showed that psoriasis was
      associated with increased EAT volume independently of visceral abdominal fat and
      with subclinical atherosclerosis. Within psoriasis patients EAT volume was
      independently associated with CAC. EAT may be another important contributor to
      the higher cardiovascular risk observed in psoriasis.

PMID- 24750320
TI  - Cryptococcal meningitis post autologous stem cell transplantation.
AB  - Disseminated Cryptococcus disease occurs in patients with defective T-cell
      immunity. Cryptococcal meningitis following autologous stem cell transplant (SCT)
      has been described previously in only 1 patient, 4 months post SCT and while off
      antifungal prophylaxis. We present a unique case of Cryptococcus meningitis pre
      engraftment after autologous SCT, while the patient was receiving fluconazole
      prophylaxis. A 41-year-old man with non-Hodgkin's lymphoma underwent autologous
      SCT. Post-transplant prophylaxis consisted of fluconazole 400 mg daily,
      levofloxacin 500 mg daily, and acyclovir 800 mg twice daily. On day 9 post
      transplant, he developed fever and headache. Peripheral white blood cell count
      (WBC) was 700/MUL. Magnetic resonance imaging of the brain showed lesions
      consistent with meningoencephalitis. Cerebrospinal fluid (CSF) analysis revealed
      a WBC of 39 with 77% lymphocytes, protein 63, glucose 38, CSF pressure 20.5 cmH2
      O, and a positive cryptococcal antigen. CSF culture confirmed Cryptococcus
      neoformans. The patient was treated with liposomal amphotericin B 5 mg/kg
      intravenously daily, and flucytosine 37.5 mg/kg orally every 6 h. He was switched
      to fluconazole 400 mg daily after 3 weeks of amphotericin therapy, with
      sterilization of the CSF with negative CSFCryptococcus antigen and negative CSF
      culture. Review of the literature revealed 9 cases of cryptococcal disease in
      recipients of SCT. Median time of onset was 64 days post transplant. Only 3
      meningitis cases were described; 2 of them after allogeneic SCT. Fungal
      prophylaxis with fluconazole post autologous SCT is recommended at least through
      engraftment, and for up to 100 days in high-risk patients. A high index of
      suspicion is needed to diagnose and treat opportunistic infections, especially in
      the face of immunosuppression and despite adequate prophylaxis. Infection is
      usually fatal without treatment, thus prompt diagnosis and therapy might be life
      saving.

PMID- 24750322
TI  - Cross-cultural measurement equivalence of the Japanese version of Revised
      Conflict Tactics Scales Short Form among Japanese men and women.
AB  - AIM: The Revised Conflict Tactics Scales Short Form (CTS2SF) is an instrument
      used to measure intimate partner violence (IPV) perpetration and victimization
      over the past 12 months. METHODS: The CTS2SF was translated into Japanese, and
      the reliability (internal consistency and 4-week test-retest reliability) and the
      concurrent and factor-based validity were examined using two waves of Internet
      surveys over an interval of 4 weeks. Participants of the survey were 393 Japanese
      men and women who were registrants of an Internet survey company. RESULTS:
      Cronbach's alpha was greater than 0.5 for most scales, while it was low (alpha =
      0.18) for sexual coercion by partner. The test-retest reliability of the binary
      variable for the presence or absence of IPV was high (Yule's Q, 0.79-1.00), and
      moderate between the scores (Spearman's rank correlation, 0.38:0.70). Concordance
      with the Buss-Perry Aggression Questionnaire, Violence Against Women Screen, and
      Kessler 6 generally indicated good concurrent validity. The results of the
      exploratory factor analysis confirmed the three-factor structure of the Japanese
      version of the CTS2SF. CONCLUSION: Although the internal consistency reliability
      was limited for some sub-scales, its moderate internal consistency and test
      retest reliability and good factor-based validity highlighted the benefit of
      using the Japanese version of the CTS2SF in a large-scale community survey where
      a shorter scale is required to assess IPV.

PMID- 24750321
TI  - Cortical evoked potentials in response to rapid balloon distension of the rectum
      and anal canal.
AB  - BACKGROUND: Neurophysiological evaluation of anorectal sensory function is
      hampered by a paucity of methods. Rapid balloon distension (RBD) has been
      introduced to describe the cerebral response to rectal distension, but it has not
      successfully been applied to the anal canal. METHODS: Nineteen healthy women
      received 30 RBDs in the rectum and the anal canal at intensities corresponding to
      sensory and unpleasantness thresholds, and response was recorded as cortical
      evoked potentials (CEPs) in 64-channels. The anal canal stimulations at
      unpleasantness level were repeated after 4 min to test the within-day
      reproducibility. CEPs were averaged, and to overcome latency variation related to
      jitter the spectral content of single sweeps was also computed. KEY RESULTS:
      Repeated stimulation of the anal canal generated CEPs with similar latencies but
      smaller amplitudes compared to those from the rectum. Due to latency jitter,
      reproducibility of averaged CEPs was lower than what was found in the rectum. The
      most reproducible feature was N2P2 peak-to-peak amplitude with intra-class
      correlation coefficient (ICC) of 0.7 and coefficient of variation (CV) of 18%.
      Spectral content of the single sweeps showed reproducibility with ICCs for all
      bands >0.8 and corresponding CVs <7%. CONCLUSIONS & INFERENCES: Cortical
      potentials evoked from the anal canal are challenged by latency jitter likely
      related to variability in muscle tone due to the distensions. Using single-sweep
      analysis, anal CEPs proved to be reproducible and should be used in future
      evaluation of the anal function.

PMID- 24750323
TI  - Fine needle aspiration cytology of lymphoproliferative lesions of the oral
      cavity.
AB  - OBJECTIVE: Oral cavity non-Hodgkin lymphoma (OCL) is a rare condition that may be
      clinically and radiologically indistinguishable from other pathologies of the
      mouth. A complete excision or adequate biopsy of the OCL may be difficult. Fine
      needle aspiration (FNA) cytology has been successfully utilized in the pre
      operative diagnosis of oral masses and in lymphoma involving other anatomical
      areas. Our experience with FNA pre-operative cytological diagnosis of 16 OCLs is
      reported herein. METHODS: The results of FNA cytology on 16 consecutive
      lymphoproliferative lesions of the oral cavity collected over an 8-year period in
      three institutions were retrieved. Sampled lesions were submucosal masses of
      different sizes bulging into the oral cavity. Rapid on-site evaluation (ROSE) and
      routine cytological staining were performed. Immunocytochemistry (ICC), flow
      cytometry (FC) and polymerase chain reaction (PCR) of the IGH (immunoglobulin
      heavy) locus were performed on additional passes according to ROSE. RESULTS:
      Fourteen OCLs, one myeloma and one florid reactive lymphoid hyperplasia (FRLH)
      were diagnosed by FNA. OCLs were diagnosed as large B-cell (eight cases) and
      small B-cell (six cases) lymphomas. Histology revealed eight diffuse large B-cell
      lymphomas (DLBCL), four lymphomas of mucosa-associated lymphoid tissue (MALT),
      two follicular lymphomas and one FRLH; no false-negative or false-positive
      results were diagnosed, but accurate subclassification was obtained in four cases
      only. CONCLUSIONS: FNA diagnosis of OCLs may be hampered by the rare incidence,
      anatomical context and difficulties in obtaining a sufficient amount of cells.
      Ancillary techniques should be used according to ROSE; a pre-operative FNA
      cytology diagnosis can avoid unnecessary extensive surgery and speed up the
      institution of therapeutic procedures.

PMID- 24750324
TI  - The effect of glass fiber-reinforced epoxy resin dowel diameter on the fracture
      resistance of endodontically treated teeth.
AB  - PURPOSE: To determine the effect of glass fiber-reinforced epoxy resin (FRC)
      dowels of different diameters on the failure load of endodontically treated teeth
      with different remaining dentine and reinforcing resin composite (RRC)
      thicknesses and the mode of failure in each group. MATERIALS AND METHODS: Fifty
      extracted intact human maxillary central incisors were decoronated 2 mm incisal
      to the buccal cementoenamel junction and endodontically treated. The teeth were
      randomly assigned to one of five groups (n = 10): group B, dowel space prepared
      with size 0 dowel drill/size 0 FRC dowel/no RRC; group W, size 1 dowel space/size
      1 FRC dowel/no RRC; group R, size 3 dowel space/size 3 FRC dowel/no RRC; group
      WR, size 3 dowel space/size 1 FRC dowel/RRC; group BR, size 3 dowel space/size 0
      FRC dowel/RRC. Ferrules of 2 and 0.5 mm were prepared at the facio-lingual and
      proximal margin respectively. All specimens were restored with a Ni-Cr crown,
      thermocycled and loaded at 135 degrees  from the long axis in a universal testing
      machine at a 0.5 mm/min crosshead speed until fracture. Data were analyzed using
      ANOVA followed by post hoc comparisons (Bonferroni) with alpha = 0.05. RESULTS:
      Mean failure loads (N) for groups B, W, R, WR, and BR were as follows: 1406 (SD =
      376), 1259 (379), 1085 (528), 959 (200), and 816 (298). Significant differences
      were found between groups B and BR. Group B had the highest favorable failure
      mode. CONCLUSION: Within the limitations of this study, the use of a smaller FRC
      dowel and RRC is recommended rather than enlargement of dowel spaces to
      accurately fit larger FRC dowels, as the enlargement of dowel space may increase
      the risk of unfavorable failure.

PMID- 24750325
TI  - Cardiovascular risk markers and thyroid status in young Indian women with
      polycystic ovarian syndrome: a case-control study.
AB  - AIM: To study thyroid function profile, atherogenic markers and their association
      in young women with PCOS. METHODS: Thirty women aged 15-30 years with PCOS
      (married and unmarried) and an equal number of age-matched controls were included
      in this study. The following parameters were assessed: thyroid-stimulating
      hormone (TSH), free triiodothyronine (FT3), tetraiodothyronine (FT4), total
      cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL
      C), low-density lipoprotein cholesterol (LDL-C), very low-density lipoprotein
      cholesterol (VLDL-C) homocysteine (HCY), lipoprotein(a) (Lp[a]) levels. RESULTS:
      Thyroid function tests were within normal ranges in all the cases and controls.
      The following parameters were significantly elevated in women with PCOS compared
      to controls: serum TC, TG, LDL,VLDL, HCY and Lp(a). Married women with PCOS had
      significantly higher levels of TC, TG, VLDL-C, LDL-C, HCY and Lp(a). Among
      unmarried PCOS cases, HCY levels were found to be significantly higher compared
      to unmarried controls. In group 1, Lp(a) levels were found to be high. In group
      2, TC, TG, LDL-C, VLDL-C, Lp(a) and HCY levels were found to be high. In group 3,
      TC, VLDL-C and Lp(a) were found to be high. CONCLUSION: Alteration in lipid
      metabolism and elevated HCY and Lp(a) levels were present in women with PCOS,
      which were independent of their thyroid status. Unmarried PCOS women are
      predisposed to develop cardiovascular diseases rather than married PCOS women.
      Group 2 PCOS women are predisposed to get cardiovascular diseases rather than
      group 1 and group 3. PCOS women need not have hypothyroidism.

PMID- 24750326
TI  - Biopsychronology: live confocal imaging of biopsies to assess organ function.
AB  - Prolonged ischemia (I) times caused by organ procurement and transport are main
      contributors to a decrease in organ function, which is further enhanced during
      reperfusion (R). This combined damage, referred to as ischemia-reperfusion injury
      (IRI), is a main contributor to delayed graft function, which leads to costly and
      lengthy follow-up treatments or even organ loss. Methods to monitor the status of
      a graft prior to transplantation are therefore highly desirable to optimize the
      clinical outcome. Here, we propose the use of fine needle biopsies, which are
      analyzed by real-time live confocal microscopy. Such a combination provides
      information about the functional and structural integrity of an organ within a
      few minutes. To confirm the feasibility of this approach, we obtained fine needle
      biopsies from rodent kidneys and exposed them to various stress conditions.
      Following the addition of a range of live stains, biopsies were monitored for
      mitochondrial function, cell viability, and tissue integrity using confocal live
      cell imaging. Our data demonstrate that this procedure requires minimal time for
      sample preparation and data acquisition and is well suitable to record organ
      damage resulting from unphysiological stress. 

PMID- 24750328
TI  - A novel INF2 mutation in a Korean family with autosomal dominant intermediate
      Charcot-Marie-Tooth disease and focal segmental glomerulosclerosis.
AB  - Mutations in the inverted formin-2 (INF2) gene were recently identified in
      patients with autosomal dominant intermediate Charcot-Marie-Tooth (DI-CMT)
      disease and focal segmental glomerulosclerosis (FSGS). Here, we identified a
      novel p.L132P INF2 mutation in a Korean family with DI-CMT and FSGS by whole
      exome sequencing. This mutation was cosegregated with affected individuals in the
      family and was not found in the 300 controls. The two affected members exhibited
      juvenile onset sensorimotor polyneuropathy and FSGS. Nerve conduction studies
      showed an intermediate range of motor nerve conduction velocities. We report a
      novel INF2 mutation in a family with DI-CMT and FSGS as the first case in
      Koreans. The INF2 mutation appears to be a major cause of CMT with FSGS. 

PMID- 24750327
TI  - HCV E1E2-MF59 vaccine in chronic hepatitis C patients treated with PEG-IFNalpha2a
      and Ribavirin: a randomized controlled trial.
AB  - Hepatitis C virus (HCV) vaccines may be able to increase viral clearance in
      combination with antiviral therapy. We analysed viral dynamics and HCV-specific
      immune response during retreatment for experienced patients in a phase Ib study
      with E1E2MF59 vaccine. Seventy-eight genotype 1a/1b patients [relapsers (30),
      partial responders (16) and nonresponders (32) to interferon-(IFN)/ribavirin
      (RBV)] were randomly assigned to vaccine (V:23), Peg-IFNalpha2a-180-ug/qw and
      ribavirin 1000-1200-mg/qd for 48 weeks (P/R:25), or their combination (P/R +
      V:30). Vaccine (100 MUg/0.5 mL) was administered intramuscularly at week 0-4-8-12
      24-28-32-36. Neutralizing of binding (NOB) antibodies and lymphocyte
      proliferation assay (LPA) for E1E2-specific-CD4 + T cells were performed at week
      0-12-16-48. Viral kinetics were analysed up to week 16. The vaccine was safe, and
      a sustained virological response (SVR) was achieved in 4 P/R + V and 2 P/R
      patients. Higher SVR rates were observed in prior relapsers (P/R + V = 27.3%; P/R
      = 12.5%). Higher NOB titres and LPA indexes were found at week 12 and 16 in P/R +
      V as compared to P/R patients (P = 0.023 and 0.025, P = 0.019 and <0.001,
      respectively). Among the 22 patients with the strongest direct antiviral effects
      of IFN (epsilon >= 0.800), those treated with P/R + V (10) reached lower HCV-RNA
      levels (P = 0.026) at week 16. HCV E1E2MF59 vaccine in combination with Peg
      IFNalpha2a + RBV was safe and elicited E1E2 neutralizing antibodies and specific
      CD4 + T cell proliferation. Upon early response to IFN, vaccinations were
      associated with an enhanced second phase viral load decline. These results prompt
      phase II trials in combination with new antiviral therapies.

PMID- 24750329
TI  - Mutational screening of the NR5A1 in azoospermia.
AB  - Nuclear receptor subfamily 5 group A member 1 (NR5A1) encodes a nuclear receptor
      that regulates transcription of multiple genes involved in adrenal and gonadal
      development, steroidogenesis and the reproductive axis. Human mutations in
      NR5A1were initially found in two 46, XY female patients suffering from severe
      gonadal dysgenesis and primary adrenal failure. However, more recent case reports
      have suggested that heterozygous mutations in NR5A1 may also contribute to the
      male infertility aetiology. We have analysed the coding sequence of NR5A1 in a
      cohort of 90 well-characterised idiopathic Iranian azoospermic infertile men
      versus 112 fertile men. Heterozygous NR5A1 mutations were found in 2 of 90 (2.2%)
      of cases. These two patients harboured missense mutations within the hinge region
      (p.P97T) and ligand-binding domain (p.E237K) of the NR5A1 protein. In silico
      analysis of the mutations showed that founded mutations could be detrimental. In
      conclusion, findings of the current and previous studies suggest that mutations
      in the NR5A1 gene are not common in azoospermia, and male infertility and
      inclusion of NR5A1 mutation screening in the diagnostic workup of male
      infertility may seem unnecessary. 

PMID- 24750330
TI  - Factors influencing isometric exercise training-induced reductions in resting
      blood pressure.
AB  - Hypertension is a major health concern, and current recommendations for blood
      pressure management (lifestyle modifications and pharmacological intervention)
      have not been universally successful. For two decades, isometric exercise
      training (IET) has become established as effective at reducing in resting BP
      (RBP) in a short period (4-10 weeks). The most common IET modes have comprised
      isometric handgrip (IHG) or isometric bilateral leg (IBL) training and 4 * 2-min
      contractions at ~20-50% maximal voluntary contraction with 1-5-min rest between.
      Although this type of exercise training could have important implications, for
      hypertensive patients and in preventing hypertension development, little is known
      about the mechanisms responsible for IET-induced RBP reductions. This uncertainty
      derives from a lack of understanding concerning the most effective IET programs
      for specific populations. Possible influential factors and mechanisms include
      age, sex, pre-existing disease and medication, and IET-induced adaptations in the
      exercising muscle and nervous system, which are discussed in this review.
      Designing effective IET programs may involve manipulation of exercise intensity,
      frequency, duration and mode, as well as consideration of yet discovered
      mechanisms for RBP reductions. We call for additional research designed to
      understand more about the mechanisms involved in IET-induced RBP reductions for
      maximum effectiveness. 

PMID- 24750331
TI  - Mantle cell lymphoma and diffuse large B-cell lymphoma of the testis: a unique
      case of composite non-Hodgkin lymphoma.
AB  - Primary testicular non-Hodgkin lymphoma (NHL) is a rare entity with the most
      common histologic subtype consisting of diffuse large B-cell lymphoma (DLBCL).
      Patients with primary testicular lymphoma (PTL) have a poor prognosis and a
      higher propensity for relapse. Also rare are composite lymphomas (CL) defined as
      two or more morphologically and phenotypically distinct lymphomas coexisting in a
      single organ or tissue. Here we present the first reported case of primary
      testicular composite lymphoma consisting of DLBCL and mantle cell lymphoma (MCL).

PMID- 24750332
TI  - Generative models versus underlying symmetries to explain biological pattern.
AB  - Mathematical models play an increasingly important role in the interpretation of
      biological experiments. Studies often present a model that generates the
      observations, connecting hypothesized process to an observed pattern. Such
      generative models confirm the plausibility of an explanation and make testable
      hypotheses for further experiments. However, studies rarely consider the broad
      family of alternative models that match the same observed pattern. The symmetries
      that define the broad class of matching models are in fact the only aspects of
      information truly revealed by observed pattern. Commonly observed patterns derive
      from simple underlying symmetries. This article illustrates the problem by
      showing the symmetry associated with the observed rate of increase in fitness in
      a constant environment. That underlying symmetry reveals how each particular
      generative model defines a single example within the broad class of matching
      models. Further progress on the relation between pattern and process requires
      deeper consideration of the underlying symmetries. 

PMID- 24750333
TI  - Exome resequencing reveals signatures of demographic and adaptive processes
      across the genome and range of black cottonwood (Populus trichocarpa).
AB  - Extant variation in temperate and boreal plant species has been influenced by
      both demographic histories associated with Pleistocene glacial cycles and
      adaptation to local climate. We used sequence capture to investigate the role of
      these neutral and adaptive processes in shaping diversity in black cottonwood
      (Populus trichocarpa). Nucleotide diversity and Tajima's D were lowest at
      replacement sites and highest at intergenic sites, while LD showed the opposite
      pattern. With samples grouped into three populations arrayed latitudinally,
      effective population size was highest in the north, followed by south and centre,
      and LD was highest in the south followed by the north and centre, suggesting a
      possible northern glacial refuge. FST outlier analysis revealed that promoter, 5'
      UTR and intronic sites were enriched for outliers compared with coding regions,
      while no outliers were found among intergenic sites. Codon usage bias was
      evident, and genes with synonymous outliers had 30% higher average expression
      compared with genes containing replacement outliers. These results suggest
      divergent selection related to regulation of gene expression is important to
      local adaptation in P. trichocarpa. Finally, within-population selective sweeps
      were much more pronounced in the central population than in putative northern and
      southern refugia, which may reflect the different demographic histories of the
      populations and concomitant effects on signatures of genetic hitchhiking from
      standing variation.

PMID- 24750334
TI  - Tobacco particulate matter self-administration in rats: differential effects of
      tobacco type.
AB  - Nicotine self-administration in rats is the most widely used animal model of
      tobacco dependence. There is increasing evidence, however, that non-nicotinic
      constituents in smoke contribute to addiction and that different tobacco products
      contain varying levels of these constituents. The present study firstly sought to
      compare self-administration of pure nicotine to tobacco particulate matter (TPM)
      to determine if there were differences in reward-efficacy attributable to the non
      nicotine constituents. Secondly, cigarette and roll-your-own (RYO) TPM groups
      were included and compared to determine whether different formulations of non
      nicotinic constituents could impact reward. Briefly, male Sprague Dawley rats
      were implanted with indwelling jugular catheters for self-administration (n =
      76). The reinforcing efficacy of infusions of nicotine (0.0 or 30.0
      MUg/kg/infusion) versus cigarette/RYO TPM (with matched nicotine content) was
      determined using spontaneous acquisition of self-administration on a fixed ratio
      schedule. The progressive ratio schedule was then employed to determine the
      motivation to receive each drug and within-subject dose-response curves were also
      produced (7.5, 15.0, 30.0 and 60.0 MUg/kg/infusion nicotine). The main finding
      was that the RYO TPM was more reinforcing and produced a different profile of
      reward-related behaviour compared with both the nicotine and the cigarette TPM
      groups. The conclusions were that non-nicotinic components have a role in tobacco
      dependence and that some tobacco products could have higher abuse liability,
      irrespective of nicotine levels. 

PMID- 24750335
TI  - Retracted: Executive dysfunction in elderly diabetic patients.

PMID- 24750336
TI  - Parameters for quantifying bolus retention with high-resolution impedance
      manometry.
AB  - BACKGROUND: This study aimed to develop a methodology for quantifying esophageal
      bolus retention using a high-resolution esophageal impedance topography (EIT)
      technique. METHODS: The ability of impedance to quantify bolus retention was
      validated by comparison with concurrent fluoroscopic imaging (barium bolus) in 10
      healthy subjects. High-resolution impedance manometry (HRIM) studies without
      fluoroscopy were performed in another 15 healthy subjects to define normal values
      using saline. HRIM data from each subject were analyzed using a MATLAB program
      customized for calculating the esophageal impedance integral (EII) prior to the
      contraction wave front as EII1 and after the contraction as EII2, and presented
      as a ratio of EII2/EII1, which was compared to the percent of barium areas
      retained in the esophagus on fluoroscopy determined by a blinded reviewer. KEY
      RESULTS: In 93% (37/40) of barium swallows, the results from the EIT method were
      in agreement with fluoroscopy results with one of three patterns: (1) 25 normal
      bolus transit, (2) eight bolus stasis, and (3) four retrograde escape or reflux.
      Three swallows (8%) had slight retention identified by EIT, but no retention
      detected by fluoroscopy. The correlation between percent of bolus retained in the
      esophagus detected by fluoroscopy and percent of bolus retention (EII2/EII1)
      after swallows with EIT method was r = 0.96 (p < 0.001) in supine and r = 0.69 (p
      < 0.001) in upright position. CONCLUSIONS & INFERENCES: The EII ratio (EII2/EII1)
      is a surrogate for the fraction of retained bolus after a swallow and this metric
      may be useful in better defining esophageal function.

PMID- 24750337
TI  - Fast-growing 'giant' clear cell acanthoma detected by dermoscopy during treatment
      with infliximab in a psoriatic patient.

PMID- 24750338
TI  - Effectiveness of conventional and hydrosurgical debridement methods in reducing
      Staphylococcus aureus inoculation of equine muscle in vitro.
AB  - REASONS FOR PERFORMING STUDY: The success of primary healing of equine traumatic
      wounds is dependent on thorough debridement. A specific hydrosurgical debridement
      device (Versajet(TM) )(a) is gentle to viable tissues, yet effectively removes
      macroscopic contaminants and debris. We wished to investigate whether it is
      effective in reducing bacterial burden and whether it differs from traditional
      methods. No previous reports compare hydrosurgical debridement and conventional
      wound debridement with regard to bacterial reduction from in vitro inoculated
      soft tissue. OBJECTIVES: To assess the effectiveness of hydrosurgical debridement
      in reducing the Staphylococcus aureus load from in vitro inoculated equine muscle
      compared with conventional wound debridement methods. STUDY DESIGN: In vitro
      experimental study. METHODS: The surface of equine masseter muscle was inoculated
      with a S. aureus broth and subsequently debrided using one of the following 4
      methods: saline irrigation; sharp debridement; saline irrigation and sharp
      debridement; or hydrosurgical debridement. Tissue samples for quantitative
      cultures were collected before and after debridement, and the colony-forming
      units per gram of tissue were calculated and log transformed. The reductions in
      bacterial counts were analysed statistically using Wilcoxon signed-rank tests and
      Friedman two-way ANOVA. RESULTS: Hydrosurgical debridement was more effective
      than conventional debridement methods in reducing the S. aureus load (P<0.05).
      Hydrosurgical debridement reduced the bacterial load by 99.7%, in comparison to
      saline irrigation and sharp debridement (87.4%), sharp debridement (82.2%) and
      saline irrigation (46.0%). CONCLUSIONS: Hydrosurgical debridement reduces the S.
      aureus load from in vitro contaminated equine muscle significantly more than
      conventional debridement methods.

PMID- 24750339
TI  - Initial prevalence of anal human papilloma virus infection in liver transplant
      recipients.
AB  - Although liver transplant recipients are at increased risk of human papilloma
      virus (HPV)-related anal cancer, limited data are available regarding the initial
      prevalence of anal HPV infection in this population. Anal swabs collected from 50
      liver transplant recipients within the first three postoperative weeks were
      subjected to real-time polymerase chain reaction for detection of the four HPV
      genotypes: 6, 11, 16, and 18. Predictors of any, low-risk, and high-risk anal HPV
      infection were evaluated. Overall, the prevalence of any anal HPV infection was
      18.0%, with the corresponding rates for high- and low-risk HPV genotypes being
      8.0% and 10.0%, respectively. Infection with any type of anal HPV was higher in
      patients with hepatitis B virus (HBV) infection (P = 0.027), >=3 sexual partners
      (P = 0.031), and alcoholic liver disease (P = 0.063). HBV infection was the only
      factor significantly associated with high-risk HPV infection (P = 0.038). Male
      sex (P = 0.050), age >=52 years (P = 0.016), >=30 sexual partners (P = 0.003),
      age at first intercourse <=18 years (P = 0.045), and time since first intercourse
      >=38 years (P = 0.012) were identified as predictors of low-risk HPV infection.
      These results indicate that HPV vaccination of liver transplant candidates and
      screening for anal HPV infection in high-risk groups should be considered. 

PMID- 24750340
TI  - A novel coping design to decrease maximum principal stress in zirconia ceramic
      restorations.
AB  - PURPOSE: The objective of this study was to evaluate the influence of coping
      design modifications on maximum first principal stress (MPS) in a mathematical
      zirconia ceramic crown model. MATERIALS AND METHODS: For a nonlinear, 3D finite
      element analysis, a simplified tooth model was built on the basis of the average
      dimensions of mandibular second molars. Virtual tooth reduction was performed to
      model an abutment with a flat occlusal surface and 16 degrees  convergence angle
      between facing walls. The cement layer was set to a thickness of 100 MUm. Three
      different copings-one with 0.5-mm constant thickness; one with constant thickness
      and extended lingual and proximal collars; and a novel design with zirconia beam
      reinforcement-were designed to simulate zirconia ceramic restorations. The novel
      design had strategically positioned zirconia beams on the lingual and marginal
      ridges to protect veneer ceramics, and was divided into three subdesigns
      according to the width of the zirconia beam (0.5, 0.8, and 1 mm). Combinations of
      vertical and horizontal load were applied over the distolingual marginal ridge,
      and the MPSs were evaluated. RESULTS: The novel design showed the lowest MPS in
      veneer ceramics under most loading conditions. The only exception to this was the
      novel design with a 0.5-mm zirconia beam width under mesial horizontal load.
      CONCLUSIONS: Compared to constant thickness coping with or without extended
      collars, the novel coping design reduced MPS in veneer ceramics; however, narrow
      zirconia beams should be avoided to prevent elevations in MPS in veneer ceramic
      layers.

PMID- 24750341
TI  - Predicting mortality in people with type 2 diabetes mellitus after major
      complications: a study using Swedish National Diabetes Register data.
AB  - AIM: To predict mortality risk and life expectancy for patients with type 2
      diabetes after a major diabetes-related complication. METHODS: The study sample,
      taken from the Swedish National Diabetes Register, consisted of 20 836 people
      with type 2 diabetes who had their first major complication (myocardial
      infarction, stroke, heart failure, amputation or renal failure) between January
      2001 and December 2007. A Gompertz proportional hazards model was derived which
      determined significant risk factors associated with mortality and was used to
      estimate life expectancies. RESULTS: Risk of death changed over time according to
      type of complication, with myocardial infarction initally having the highest
      initial risk of death, but after the first month, the risk was higher for heart
      failure, renal failure and amputation. Other factors that increased the risk of
      death were male gender (hazard ratio 1.06, 95% CI 1.02-1.12), longer duration of
      diabetes (hazard ratio 1.07 per 10 years, 95% CI 1.04-1.10), smoking (hazard
      ratio 1.51, 95% CI 1.40-1.63) and macroalbuminuria (hazard ratio 1.14, 95% CI
      1.06-1.22). Low BMI, low systolic blood pressure and low estimated GFR also
      increased mortality risk. Life expectancy was highest after a stroke, myocardial
      infarction or heart failure, lower after amputation and lowest after renal
      failure. Smoking and poor renal function were the risk factors which had the
      largest impact on reducing life expectancy. CONCLUSIONS: Risk of death and life
      expectancy differs substantially among the major complications of diabetes, and
      factors significantly increasing risk included smoking, low estimated GFR and
      albuminuria.

PMID- 24750342
TI  - Social oocyte freezing: a survey among Singaporean female medical students.
AB  - AIM: Social oocyte freezing has gained increasing interest worldwide. We
      conducted a cross-sectional survey on 129 female medical students in Singapore to
      assess their mindset and attitudes toward fertility and social oocyte freezing.
      METHODS: An anonymous online survey was conducted among female medical students
      in Singapore. The desired sample size was 100 participants. Their awareness of
      the existence of social oocyte freezing was first assessed. An information
      leaflet was provided subsequently, followed by a more detailed questionnaire. The
      questions focused on their awareness of age-related fertility decline and their
      intentions for social oocyte freezing if made available. RESULTS: One hundred and
      twenty-nine female students participated in the electronic survey, of whom 36.4%
      had heard of social oocyte freezing. Of these, 70% had personally considered
      taking up this option. However, after reading the information leaflet, only 48.9%
      would still consider this option. Of the total, 89.9% considered themselves too
      old for pregnancy after the age of 35 years, 37.2% would delay family planning
      for their career, 45.7% would consider social oocyte freezing to postpone family
      planning for their career, 46.5% would consider oocyte freezing if they had no
      suitable partners yet, 50.4% may consider freezing their eggs after the age of 30
      years and 71.3% may be more amenable to oocyte freezing if government subsidy is
      available. CONCLUSION: We hypothesize that social oocyte freezing may be a viable
      option for single young women who wish to delay child-bearing for 'reproductive
      insurance', so long as this is done with appropriate informed consent with non
      directive counseling.

PMID- 24750343
TI  - Efficacy and safety of hepatitis A vaccination in kidney transplant recipients.
AB  - BACKGROUND: In recent years, symptomatic hepatitis A virus (HAV) infection has
      been reported with increasing frequency in Korea. Therefore, HAV vaccination
      should be considered in kidney transplant recipients (KTRs). The study
      investigated the efficacy and safety of HAV vaccination in KTRs under modern
      triple immunosuppressive agents. METHODS: We evaluated the seroprevalence of anti
      HAV immunoglobulin-G (IgG) in KTRs who had visited the Seoul National University
      Hospital from March 2011 to August 2012. Seronegative patients were immunized
      with 2 doses of HAV vaccine at a 6-month interval. Seroconversion of anti-HAV IgG
      was determined 1 month after the second vaccine dose, and adverse effects were
      monitored after each vaccination. RESULTS: Among a total 416 KTRs who were
      screened, 338 (81.2%) patients were seropositive for anti-HAV IgG. However, among
      patients who were under 40 years of age, only 31.8% were seropositive. Fifty-two
      seronegative recipients (mean age 34.1 years, 71.2% male) had received 2 doses of
      vaccine, and only 14 of these patients (26.9%) showed seroconversion. Vaccine
      responders had lower serum creatinine (1.19 +/- 0.24 vs. 1.45 +/- 0.49 mg/dL, P =
      0.013), higher plasma hemoglobin levels (14.4 +/- 1.9 vs. 12.8 +/- 1.8 g/dL, P =
      0.006), and had lower tacrolimus use than cyclosporine use (57.1% vs. 84.2%, P =
      0.040) compared with non-responders. Responders had a tendency of taking lower
      dose of prednisolone (3.5 +/- 1.6 vs. 4.3 +/- 1.2 mg/day, P = 0.076), and having
      fewer infection events (14.3 vs. 40.5%, P = 0.076). Multivariate analysis
      indicated that higher hemoglobin levels and lower serum creatinine levels were
      significant prognostic factors for seroconversion. Overall, the vaccine was well
      tolerated in all patients. CONCLUSION: HAV IgG screening is necessary for KTRs,
      especially young recipients. HAV vaccination was safe in KTRs; however, poor
      response to HAV vaccination makes it important to identify seronegative patients
      as early as possible and vaccinate them before end-stage renal disease occurs.

PMID- 24750344
TI  - Efficient expression of a soluble lipid transfer protein (LTP) of Platanus
      orientalis using short peptide tags and structural comparison with the natural
      form.
AB  - Successful recombinant allergen-based immunotherapy has drawn a great deal of
      attention to use recombinant allergens for new therapeutic and/or diagnostic
      strategies. The Escherichia coli expression system is frequently used to produce
      recombinant allergens; however, protein expression in E. coli often results in
      inclusion bodies. Here, we focused on the expression of two recombinant soluble
      forms of Pla or 3 using solubility-enhancing peptide tags, human immune
      deficiency virus type 1 transactivator of transcription core domain and poly
      arginine-lysine: rTAT-Pla or 3 and rPoly-Arg-Lys-Pla or 3. Structural
      characteristics and IgE reactivity of purified recombinant proteins were compared
      with natural Pla or 3 (nPla or 3) isolated from Platanus orientalis using
      circular dichroism spectra, fluorescence spectroscopy, and immunoblotting.
      Likewise, intrinsic viscosity and Stokes radius of the natural and recombinant
      Pla or 3 allergens were determined to analyze structural compactness in aqueous
      media. The results indicate high-level solubility and efficient expression of the
      fusion proteins (rTAT-Pla or 3 and rPoly-Arg-Lys-Pla or 3) compared with the wild
      type recombinant. Furthermore, the similar structural characteristics and IgE
      binding activities of the fusion proteins to nPla or 3 provide a promising tool
      for allergy diagnosis and treatment. 

PMID- 24750345
TI  - ITPA genetic variants influence efficacy of PEG-IFN/RBV therapy in older patients
      infected with HCV genotype 1 and favourable IL28B type.
AB  - Inosine triphosphatase (ITPA) genetic variants are strongly associated with
      ribavirin (RBV)-induced anaemia during pegylated interferon (PEG-IFN) plus RBV
      therapy. However, the treatment efficacy of ITPA genetic variants has not been
      fully explored. We enrolled 309 individuals infected with hepatitis C virus
      genotype 1, who were treated with PEG-IFN plus RBV for 48 weeks. The ITPA SNP:
      rs1127354 and IL28B SNP: rs8099917 were genotyped. We examined the risk factors
      for severe anaemia up to week 12 after the start of treatment and treatment
      efficacy. The incidence of severe anaemia, >= 3 g/dL reduction or <10 g/dL of
      haemoglobin (Hb) up to week 12, was more frequent in patients with CC at
      rs1127354 [65% (145/224), 33% (73/224)] than in those with CA/AA [25% (21/85), 6%
      (8/85)] (P < 0.0001). ITPA genotype, pretreatment Hb level and age were
      independent predictive factors for severe anaemia: Hb < 10 g/dL. In IL28B
      favourable type, the sustained virologic response rate was higher in >= 60-year
      old patients with CA/AA than in those with CC [71% (22/31) vs 40% (26/65), P =
      0.005], although there was no significant difference in treatment efficacy
      according to ITPA genetic variants in the <60-year-old patients. The proportion
      of patients administered >= 80% of the dosage of RBV was significantly higher in
      the patients with CA/AA than in those with CC (P = 0.025), resulting in a lower
      relapse rate. In conclusion, ITPA genetic variants were associated with severe
      RBV-induced anaemia and could influence the efficacy of PEG-IFN plus RBV
      treatment among elderly patients with IL28B favourable type.

PMID- 24750346
TI  - Involuted facial infantile hemangioma with fatty replacement successfully treated
      with surgery.

PMID- 24750347
TI  - Mechanism of dorsal column stimulation to treat neuropathic but not nociceptive
      pain: analysis with a computational model.
AB  - OBJECTIVE: Stimulation of axons within the dorsal columns of the human spinal
      cord has become a widely used therapy to treat refractory neuropathic pain. The
      mechanisms have yet to be fully elucidated and may even be contrary to standard
      "gate control theory." Our hypothesis is that a computational model provides a
      plausible description of the mechanism by which dorsal column stimulation (DCS)
      inhibits wide dynamic range (WDR) cell output in a neuropathic model but not in a
      nociceptive pain model. MATERIALS AND METHODS: We created a computational model
      of the human spinal cord involving approximately 360,000 individual neurons and
      dendritic processing of some 60 million synapses--the most elaborate dynamic
      computational model of the human spinal cord to date. Neuropathic and nociceptive
      "pain" signals were created by activating topographically isolated regions of
      excitatory interneurons and high-threshold nociceptive fiber inputs, driving
      analogous regions of WDR neurons. Dorsal column fiber activity was then added at
      clinically relevant levels (e.g., Abeta firing rate between 0 and 110 Hz by using
      a 210-MUsec pulse width, 50-150 Hz frequency, at 1-3 V amplitude). RESULTS:
      Analysis of the nociceptive pain, neuropathic pain, and modulated circuits shows
      that, in contradiction to gate control theory, 1) nociceptive and neuropathic
      pain signaling must be distinct, and 2) DCS neuromodulation predominantly affects
      the neuropathic signal only, inhibiting centrally sensitized pathological neuron
      groups and ultimately the WDR pain transmission cells. CONCLUSION: We offer a
      different set of necessary premises than gate control theory to explain
      neuropathic pain inhibition and the relative lack of nociceptive pain inhibition
      by using retrograde DCS. Hypotheses regarding not only the pain relief mechanisms
      of DCS were made but also regarding the circuitry of pain itself, both
      nociceptive and neuropathic. These hypotheses and further use of the model may
      lead to novel stimulation paradigms.

PMID- 24750348
TI  - Impression cytology diagnosis of ulcerative eyelid malignancy.
AB  - OBJECTIVE: The utility of impression cytology in ocular diseases has
      predominantly been restricted to the diagnosis of dry eye, limbal stem cell
      deficiency and conjunctival neoplasias. Its role in malignant eyelid lesions
      remains largely unexplored. Although scrape cytology is more popular for
      cutaneous lesions, impression cytology, being non-traumatic, has an advantage in
      small and delicate areas such as the eyelid. The present study has been designed
      to evaluate its role in the diagnosis and management of malignant eyelid lesions.
      METHODS: Thirty-two histopathologically proven malignant eyelid lesions diagnosed
      over a 2-year period, including 13 basal cell carcinomas, 11 sebaceous
      carcinomas, four squamous cell carcinomas, two malignant melanomas and two poorly
      differentiated carcinomas, formed the study group. RESULTS: The results of
      impression cytology were compared with those of histopathology in the study group
      and with an age- and sex-matched group of benign cases as controls. The
      sensitivity of impression cytology was 84% (27/32) for the diagnosis of
      malignancy and 28% (9/32) for categorization of the type of malignancy.
      CONCLUSIONS: Impression cytology is a simple, useful, non-invasive technique for
      the detection of malignant ulcerative eyelid lesions. It is especially useful as
      a follow-up technique for the detection of recurrences.

PMID- 24750349
TI  - MicroRNA-130a regulates autophagy of endothelial progenitor cells through Runx3.
AB  - Dysfunction of endothelial progenitor cells (EPC) contribute to diabetic vascular
      disease. MicroRNAs (miRNAs) are key regulators of diverse cellular processes,
      including angiogenesis. We recently reported that downregulated miR-130a in
      patients with Type 2 diabetes mellitus (DM) results in EPC dysfunction, including
      increased apoptosis, likely via its target runt-related transcription factor 3
      (Runx3). However, whether miR-130a affects the autophagy of EPC is unknown. The
      aim of the present study was to explore the effects of miR-130a on the autophagy
      and cell death of EPC, as well as their expression of Beclin 1 (BECN1; an
      initiator of autophagosome formation) and the anti-apoptotic protein Bcl2 (which
      binds to and inactivates BECN1), and the role of Runx3 in mediating these
      effects. The EPC were cultured from peripheral blood mononuclear cells of
      diabetic patients and non-diabetic controls. Cells were transfected with an miR
      130a inhibitor, or mimic-miR-130a or mimic-miR-130a plus lentiviral vector
      expressing Runx3 to manipulate miR-130a and/or Runx3 levels. The number of
      autophagosomes was counted under transmission electron microscopy and cell death
      was examined by flow cytometry. The mRNA expression of Beclin1 was measured by
      real-time polymerase chain reaction and the protein expression of Beclin1 and
      Bcl2 was determined by western blotting. Both the number of autophagosomes and
      Beclin1 expression were increased in EPC from patients with DM. Inhibition of miR
      130a increased the number of autophagosomes and Beclin1 expression, but
      attenuated Bcl2 expression. Overexpression of miR-130a decreased the number of
      autophagosomes, cell death and Beclin1 expression, but promoted Bcl2 expression;
      these effects were mediated by Runx3. In conclusion, miR-130a is important for
      maintaining normal autophagy levels and promoting the survival of EPC via
      regulation of Bcl-2 and Beclin1 expression, via Runx3. MiR-130a may be a
      regulator linking apoptosis and the autophagy of EPC. 

PMID- 24750350
TI  - Clinical and microbiological impact of discontinuation of fluoroquinolone
      prophylaxis in patients with prolonged profound neutropenia.
AB  - BACKGROUND: Infections remain a leading cause of morbidity and mortality in
      patients with reduced immunity caused by haematological disease and chemotherapy
      induced neutropenia. We evaluated the clinical and microbiological impact of
      discontinuing fluoroquinolone prophylaxis in these patients. METHODS: We analysed
      154 admissions in three sequential periods of 8 months: long-standing use,
      discontinuation of prophylaxis and reintroduction of prophylaxis. Clinical
      endpoints were occurrence of febrile neutropenia, bacteraemia, severe sepsis,
      septic shock, response to antibiotic therapy, total antibiotic consumption and
      duration of hospital stay. Microbiological analysis included bacterial isolates
      from stool and blood cultures and their resistance pattern. RESULTS: No
      significant increase in serious infectious complications was seen with the
      discontinuation of prophylaxis. The overall incidence of bacteraemia did not
      change, but a higher proportion of bacterial isolates were Gram-negative (22.2%
      vs. 5.9% & 8.6%; P = 0.030), more often multisusceptible (50% vs. 0%) and less
      fluoroquinolone resistant (10% vs. 100%). Screening of stools showed a higher
      prevalence of organisms in the discontinuation period (86.7% vs. 37.3% & 55.2%; P
      <= 0.001), but they were more frequently multisusceptible (53.8% vs. 10.5% &
      6.3%; P <= 0.001). After discontinuation of prophylaxis, fluoroquinolone
      resistance decreased rapidly from 73.7 to 7.7%, in association with a significant
      decrease in extended spectrum beta-lactamase (ESBL)-producing isolates from 42.1
      to 10.3%. Resistance figures immediately returned to prediscontinuation values
      after reinstitution of prophylaxis. CONCLUSIONS: No clinically relevant short
      term drawbacks were observed with the discontinuation of fluoroquinolone
      prophylaxis in patients with chemotherapy-induced prolonged profound neutropenia,
      which led to a significant decrease in fluoroquinolone resistance as well as
      occurrence of ESBL-producing isolates.

PMID- 24750351
TI  - Cardiovascular risk and lifestyle habits of consumers of a phytosterol-enriched
      yogurt in a real-life setting.
AB  - BACKGROUND: Data on the characteristics of consumers of phytosterol-enriched
      products and modalities of consumption are rare. An observational study
      evaluating the lifestyle characteristics and cardiovascular risk (CVR) profile of
      phytosterol-enriched yogurt consumers was performed in France. METHODS: Subjects
      were recruited from general practitioners via electronic medical records. Data
      were obtained from 358 consumers and 422 nonconsumers with 519 subject
      questionnaires (243 consumers, 276 nonconsumers; 67% response). RESULTS:
      Consumers had more cardiovascular risk factors than nonconsumers (2.0 +/- 1.5
      versus 1.6 +/- 1.4; P < 0.001) and a higher 10-year SCORE cardiovascular risk
      (1.8 +/- 2.0% versus 1.6 +/- 2.2%; P = 0.008); they were older (P = 0.030) and
      had a higher incidence of hypercholesterolaemia (P < 0.001) and family or
      personal history of heart disease (P = 0.023/P = 0.026, respectively). Among
      consumers not on cholesterol-lowering medication, 99% were eligible for lifestyle
      interventions and 56% were eligible for lipid-lowering drug according to European
      guidelines. Consumers had a healthier lifestyle, with a higher (fruit/vegetable -
      saturated fatty acid) score than nonconsumers (P = 0.035), focused more on low
      intensity leisure activity (P = 0.023), spent more time travelling by foot or
      bicycle (P = 0.012) and were more likely to act to reduce CVR. Phytosterol
      enriched yogurt intake conformed to recommendations in two-thirds of consumers
      and was mainly consumed because of concerns over cholesterol levels and CVR.
      CONCLUSIONS: The higher cardiovascular disease risk profile of phytosterol
      enriched yogurt consumers corresponds to a population for whom European
      guidelines recommend lifestyle changes to manage cholesterol. The coherence of
      the data in terms of risk factors, adherence to lifestyle recommendations and the
      consumption of phytosterol-enriched yogurt conforming to recommendations reflects
      a health-conscious consumer population.

PMID- 24750352
TI  - Different obesity phenotypes, and incident cardiovascular disease and mortality
      events in elderly Iranians: Tehran lipid and glucose study.
AB  - AIM: To determine the impact of body mass index and the presence of metabolic
      syndrome (MetS) on cardiovascular disease (CVD) and mortality events in an
      elderly Tehranian population. METHODS: A population-based cohort of 1199
      participants aged >=65 years were followed for a mean of 9.74 years. Participants
      were stratified according to body mass index categories and MetS status. Cox
      regression analyses were used to estimate the hazard ratio of CVD and mortality
      events, given overweight participants without MetS as reference. RESULT: During
      follow up, 271 CVD events and 239 deaths (106 CVD deaths) occurred. Regarding
      CVD, multivariate-adjusted hazard ratios for CVD events in normal weight and
      obese participants without MetS were 1.21 (95% CI 0.77-1.91) and 1.46 (95% CI
      0.64-3.34), respectively, and for normal weight, overweight and obese
      participants with MetS were 2.07 (95% CI 1.23-3.28), 1.72 (95% CI 1.13-2.62), and
      1.53 (95% CI 0.95-2.45), respectively. Corresponding hazard ratios for CVD
      mortality were 2.08 (95% CI 0.93-4.82), 1.07 (95% CI 0.13-8.78), 3.71 (95% CI
      1.55-8.85), 2.42 (95% CI 1.06-5.51) and 3.31 (95% CI 1.39-7.88), and for all
      cause mortality were 1.41 (95% CI 0.9-2.23), 1.33 (95% CI 0.51-3.47), 1.84 (95%
      CI 1.1-3.09), 1.46 (95% CI 0.93-2.34) and 1.5 (95% CI 0.91-2.56), respectively.
      In the presence of diabetes in place of MetS, all of the diabetic participants
      regardless of body mass index category highlighted a significant risk for CVD and
      mortality events. CONCLUSION: Among the elderly population, the presence of MetS
      was necessary for exploring the risk of CVD events and its mortality; however,
      only the normal weight population with MetS had a significant risk for all-cause
      mortality

PMID- 24750353
TI  - Genome-wide single-generation signatures of local selection in the panmictic
      European eel.
AB  - Next-generation sequencing and the collection of genome-wide data allow
      identifying adaptive variation and footprints of directional selection. Using a
      large SNP data set from 259 RAD-sequenced European eel individuals (glass eels)
      from eight locations between 34 and 64(o) N, we examined the patterns of genome
      wide genetic diversity across locations. We tested for local selection by
      searching for increased population differentiation using F(ST) -based outlier
      tests and by testing for significant associations between allele frequencies and
      environmental variables. The overall low genetic differentiation found (F(ST) =
      0.0007) indicates that most of the genome is homogenized by gene flow, providing
      further evidence for genomic panmixia in the European eel. The lack of genetic
      substructuring was consistent at both nuclear and mitochondrial SNPs. Using an
      extensive number of diagnostic SNPs, results showed a low occurrence of hybrids
      between European and American eel, mainly limited to Iceland (5.9%), although
      individuals with signatures of introgression several generations back in time
      were found in mainland Europe. Despite panmixia, a small set of SNPs showed high
      genetic differentiation consistent with single-generation signatures of spatially
      varying selection acting on glass eels. After screening 50 354 SNPs, a total of
      754 potentially locally selected SNPs were identified. Candidate genes for local
      selection constituted a wide array of functions, including calcium signalling,
      neuroactive ligand-receptor interaction and circadian rhythm. Remarkably, one of
      the candidate genes identified is PERIOD, possibly related to differences in
      local photoperiod associated with the >30 degrees  difference in latitude between
      locations. Genes under selection were spread across the genome, and there were no
      large regions of increased differentiation as expected when selection occurs
      within just a single generation due to panmixia. This supports the conclusion
      that most of the genome is homogenized by gene flow that removes any effects of
      diversifying selection from each new generation.

PMID- 24750354
TI  - A case of bullous pemphigoid associated with psoriasis vulgaris showing Hailey
      Hailey disease-like histopathological changes in regenerated epidermis without
      genomic mutation in ATP2C1 or ATP2A2 gene.

PMID- 24750355
TI  - Role of alpha4- and alpha6-containing nicotinic receptors in the acquisition and
      maintenance of nicotine self-administration.
AB  - Tobacco smoking is a major cause of death and disease and as such there is a
      critical need for the development of new therapeutic approaches to treat nicotine
      addiction. Here, we utilize genetic and pharmacological tools to further
      investigate the nicotinic acetylcholine receptor (nAChR) subtypes that support
      intravenous self-administration of nicotine. alpha4-S248F mice contain a point
      mutation within the alpha4 nAChR subunit which confers increased sensitivity to
      nicotine and resistance to mecamylamine. Here, we show that acute administration
      of mecamylamine (2 mg/kg, i.p.) reduces established nicotine self-administration
      (0.05 mg/kg/infusion) in wild-type (WT), but not in alpha4-S248F heterozygous
      mice, demonstrating a role for alpha4* nAChRs in the modulation of ongoing
      nicotine self-administration. Administration of N,N-decane-1,10-diyl-bis-3
      picolinium diiodide (bPiDI), a selective alpha6beta2* nAChR antagonist, dose
      dependently (5 and 10 mg/kg, i.p.) impairs the acquisition of nicotine self
      administration and reduces established nicotine self-administration in WT mice
      when administered acutely (10 mg/kg, i.p.). This was not due to a general
      reduction in locomotor activity and the same dose of bPiDI did not affect operant
      responding for sucrose. bPiDI treatment (10 mg/kg, i.p.) also impaired both the
      acquisition and maintenance of nicotine self-administration in alpha4-S248F
      heterozygous mice. This provides further evidence for the involvement of
      alpha6beta2* nAChRs in the reinforcing effects of nicotine that underlies its
      ability to support ongoing self-administration. Taken together, selective
      targeting of alpha6beta2* or alpha4alpha6beta2* nAChRs may prove to be an
      effective strategy for the development of smoking cessation therapies. 

PMID- 24750356
TI  - Coffee consumption and the risk of latent autoimmune diabetes in adults--results
      from a Swedish case-control study.
AB  - AIMS: Coffee consumption is associated with a reduced risk of Type 2 diabetes.
      Our aim was to investigate if coffee intake may also reduce the risk of latent
      autoimmune diabetes in adults, an autoimmune form of diabetes with features of
      Type 2 diabetes. METHODS: We used data from a population-based case-control study
      with incident cases of adult onset (>= 35 years) diabetes, including 245 cases of
      latent autoimmune diabetes in adults (glutamic acid decarboxylase antibody
      positive), 759 cases of Type 2 diabetes (glutamic acid decarboxylase antibody
      negative), together with 990 control subjects without diabetes, randomly selected
      from the population. Using questionnaire information on coffee consumption, we
      estimated the odds ratio of latent autoimmune diabetes in adults and Type 2
      diabetes adjusted for age, sex, BMI, smoking, physical activity, alcohol,
      education and family history of diabetes. RESULTS: Coffee intake was inversely
      associated with Type 2 diabetes (odds ratio 0.92, 95% CI 0.87-0.98 per cup/day).
      With regard to latent autoimmune diabetes in adults, the general trend was weak
      (odds ratio 1.04, 95% CI 0.96-1.13), but stratification by degree of autoimmunity
      (median glutamic acid decarboxylase antibody levels) suggested that coffee intake
      may be associated with an increased risk of high glutamic acid decarboxylase
      antibody latent autoimmune diabetes in adults (odds ratio 1.11, 95% CI 1.00-1.23
      per cup/day). Furthermore, for every additional cup of coffee consumed per day,
      there was a 15.2% (P = 0.0268) increase in glutamic acid decarboxylase antibody
      levels. CONCLUSIONS: Our findings confirm that coffee consumption is associated
      with a reduced risk of Type 2 diabetes. Interestingly, the findings suggest that
      coffee may be associated with development of autoimmunity and possibly an
      increased risk of more Type 1-like latent autoimmune diabetes in adults.

PMID- 24750357
TI  - Prosthetic improvement of pronounced buccally positioned zygomatic implants: a
      clinical report.
AB  - This report presents a prosthetic technique for the improvement of surgically
      positioned, buccally placed zygomatic implants with the use of custom abutments
      for improved retention screw position and an esthetic implant reconstruction. The
      patient presented four zygomatic implants with pronounced buccal inclination. The
      anterior implants were inclined toward the location where the anterior artificial
      teeth should be placed during rehabilitation. As the manufacturer does not
      provide angulated abutments, we attempted the waxing and overcasting of a
      prosthetic abutment, repositioning the access holes of the prosthetic screws to a
      more palatal position. This clinical report demonstrates that abutment
      customization could be an interesting way to relocate the access holes of the
      prosthetic screws in cases of zygomatic implants with pronounced buccal
      inclination. 

PMID- 24750358
TI  - The influence of detailed maternal ethnicity on cesarean delivery: findings from
      the U.S. birth certificate in the State of Massachusetts.
AB  - BACKGROUND: Our objective was to examine the likelihood of primary cesarean
      delivery for women at low risk for the procedure in Massachusetts. METHODS: Birth
      certificate data for all births from 1996 to 2010 that were nulliparous, term,
      singleton, and vertex (NTSV; N = 427,393) were used to conduct logistic
      regression models to assess the likelihood of a cesarean delivery for each of the
      31 ethnic groups relative to self-identified "American" mothers. The results were
      compared with broad classifications of race/ethnicity more commonly employed in
      research. RESULTS: While 23.3 percent of American women had primary cesarean
      deliveries, cesarean delivery rates varied from 12.9 percent for Cambodian to
      32.4 percent for Nigerian women. Women from 21 of 30 ethnic groups had higher
      odds of a primary cesarean (range of adjusted odds ratios [AORs] 1.09-1.77),
      while only Chinese, Cambodian, and Japanese women had lower odds (range of AORs
      0.66-0.92), compared with self-identified "Americans." Using broad race/ethnicity
      categories, Non-Hispanic black, Hispanic, and "Other" women had higher odds of
      cesarean delivery relative to Non-Hispanic white women (range of AORs 1.12-1.47),
      while there were no differences for Asian or Pacific Islander women. CONCLUSIONS:
      Detailed maternal ethnicity explains the variation in NTSV cesarean delivery
      rates better than broad race/ethnicity categories. Different patterns of cesarean
      delivery between ethnic groups suggest cultural specificity related to birth
      culture.

PMID- 24750359
TI  - Effects of simulated domestic and international air travel on sleep, performance,
      and recovery for team sports.
AB  - The present study examined effects of simulated air travel on physical
      performance. In a randomized crossover design, 10 physically active males
      completed a simulated 5-h domestic flight (DOM), 24-h simulated international
      travel (INT), and a control trial (CON). The mild hypoxia, seating arrangements,
      and activity levels typically encountered during air travel were simulated in a
      normobaric, hypoxic altitude room. Physical performance was assessed in the
      afternoon of the day before (D - 1 PM) and in the morning (D + 1 AM) and
      afternoon (D + 1 PM) of the day following each trial. Mood states and
      physiological and perceptual responses to exercise were also examined at these
      time points, while sleep quantity and quality were monitored throughout each
      condition. Sleep quantity and quality were significantly reduced during INT
      compared with CON and DOM (P < 0.01). Yo-Yo Intermittent Recovery level 1 test
      performance was significantly reduced at D + 1 PM following INT compared with CON
      and DOM (P < 0.01), where performance remained unchanged (P > 0.05). Compared
      with baseline, physiological and perceptual responses to exercise, and mood
      states were exacerbated following the INT trial (P < 0.05). Attenuated
      intermittent-sprint performance following simulated international air travel may
      be due to sleep disruption during travel and the subsequent exacerbated
      physiological and perceptual markers of fatigue.

PMID- 24750360
TI  - Determination of optimum time for intravenous cannulation after induction with
      sevoflurane and nitrous oxide in children premedicated with midazolam.
AB  - BACKGROUND: It has been shown that early placement of an intravenous line in
      children administered sevoflurane anesthesia increased the incidence of
      laryngospasm and movement. However, the optimal time for safe cannulation after
      the loss of the eyelash reflex during the administration of sevoflurane and
      nitrous oxide is not known. AIM: The aim of the study was to determine the
      optimum time for intravenous cannulation after the induction of anesthesia with
      sevoflurane and nitrous oxide in children premedicated with oral midazolam.
      METHOD: We performed a prospective, observer-blinded, up-down sequential,
      allocation study, and children, aged 2-6 years, ASA physical status I, scheduled
      for an elective procedure undergoing inhalational induction were included in the
      study. Anesthesia was induced with sevoflurane and nitrous oxide after
      premedication with oral midazolam. For the first child, 4 min after the loss of
      the eyelash reflex, the intravenous cannulation was attempted by an experienced
      anesthesiologist. The time for intravenous cannulation was considered adequate if
      movement, coughing, or laryngospasm did not occur. The time for cannulation was
      increased by 15 s if the time was inadequate in the previous patient, and
      conversely, the time for cannulation was decreased by 15 s if the time was
      adequate in the previous patient. The probit test was used in the analysis of up
      down sequences. RESULTS: A total of 32 children were enrolled sequentially during
      the study period. The adequate time for effective intravenous cannulation after
      induction with sevoflurane and nitrous oxide in 50% and 95% of patients were 1.29
      min (95% confidence interval, 0.96-1.54 min) and 1.86 min (95% confidence
      interval 1.58-4.35 min), respectively. CONCLUSION: We recommend waiting 2 min for
      attempting intravenous placement following the loss of the eyelash reflex in
      children sedated with midazolam and receiving an inhalation induction with
      sevoflurane and nitrous oxide.

PMID- 24750361
TI  - Systemic inflammation in patients with chronic obstructive pulmonary disease
      undergoing percutaneous coronary intervention.
AB  - BACKGROUND AND OBJECTIVE: Systemic inflammation plays an important role in both
      chronic obstructive pulmonary disease (COPD) and coronary artery disease (CAD).
      The purpose of the present study was to assess the association of high
      sensitivity C-reactive protein (hs-CRP), a biomarker of systemic inflammation,
      with in-hospital outcomes in patients with COPD undergoing percutaneous coronary
      intervention (PCI). METHODS: A total of 378 patients with COPD who were treated
      with PCI from January 2007 through January 2012, were divided into two groups
      according to hs-CRP level at admission. Demographics, clinical, angiographic data
      and in-hospital outcomes were compared. RESULTS: Patients with elevated hs-CRP
      (>=3 mg/L) were more likely to be female and current smokers, had more severe
      airflow limitation, more hypertension, diabetes and cardiac dysfunction and had
      increased incidence of three-vessel disease and more type C lesions. Subjects
      with elevated hs-CRP were also less likely to have been prescribed with statins
      and B-blockers, perhaps. Rate of in-hospital composite major adverse
      cardiovascular events (MACEs) was higher (15.5% vs. 8.2%, P = 0.041) and hospital
      stay was longer (8.2 +/- 2.0 vs. 7.5 +/- 1.7 days, P < 0. 001) in patients with
      elevated hs-CRP. A combined analysis of MACE on the basis of airflow limitation
      and hs-CRP showed an exaggerated hazard ratio in the presence of both severe
      airflow limitation and elevated hs-CRP. In a multivariate analysis, elevated
      periprocedural hs-CRP was independently related with MACEs and hospital stay.
      CONCLUSIONS: Elevated periprocedural hs-CRP is independently and additively
      related with increased incidence of in-hospital adverse outcomes in COPD patients
      undergoing PCI.

PMID- 24750362
TI  - Synthesis of conjugated linoleic acid by the linoleate isomerase complex in food
      derived lactobacilli.
AB  - AIMS: To assess strains of lactobacilli for their capacity to produce functional
      fatty acid-conjugated linoleic acid. To assess the linoleate isomerase for CLA
      production in the most efficient CLA producer. METHODS AND RESULTS: In this
      study, strains of food-derived lactobacilli were cultured in media with linoleic
      acid and CLA production was assessed. Most of the selected strains produced CLA
      at different levels, with Lactobacillus plantarum ZS2058 being the most efficient
      CLA producer converting over 50% of linoleic acid to c9, t11-CLA and t9, t11-CLA.
      Some intermediates 10-hydroxy-cis-12-octadecenoic acid, 10-oxo-cis-12
      octadecenoic acid and 10-oxo-trans-11-octadecenoic acid were determined via GC
      MS. The genes coding the multicomponent linoleate isomerase containing myosin
      cross-reactive antigen, short-chain dehydrogenase/oxidoreductase and acetoacetate
      decarboxylase for CLA production in Lact. plantarum ZS2058 were cloned and
      expressed in Escherichia coli. With the mixture of recombinant E. coli, c9, t11
      CLA and three kinds of intermediates were produced from linoleic acid, which were
      in line with those in the lactobacilli. CONCLUSIONS: The ability for CLA
      production by lactobacilli exhibited variation. Lactobacillus plantarum and Lact.
      bulgaricus were the most efficient producers in the selected strains. Lact.
      plantarum ZS2058 converted linoleic acid to CLAs with 10-hydroxy-cis-12
      octadecenoic acid, 10-oxo-cis-12-octadecenoic acid and 10-oxo-trans-11
      octadecenoic acid as intermediates. The multiple-step reactions for CLA
      production catalysed by multicomponent linoleate isomerase in Lact. plantarum
      ZS2058 were confirmed successfully. SIGNIFICANCE AND IMPACT OF THE STUDY:
      Multicomponent linoleate isomerase provides important results for the
      illustration of the mechanism for CLA production in lactic acid bacteria. Food
      derived lactobacilli with CLA production ability offers novel opportunities for
      functional foods development.

PMID- 24750363
TI  - Long-term stimulation of Toll-like receptor 3 in primary human hepatocytes leads
      to sensitization for antiviral responses induced by poly I:C treatment.
AB  - Chronic hepatitis C infection is associated with increased expression of
      interferon-sensitive genes (ISGs) in the liver, which is, paradoxically,
      correlated with the nonresponse to interferon (IFN)-based therapies. In the
      present study PHHs were isolated from HCV-infected or uninfected patients and
      stimulated with the TLR1-9 ligands for 6-24 h. Expression of cytokines and ISGs
      was determined by ELISA and qRT-PCR. A comparative analysis was performed for
      TLR3 signalling, which was also correlated with single nucleotide polymorphisms
      (SNPs) related to HCV pathogenesis. TLR-activated PHHs produced pro-inflammatory
      and anti-inflammatory cytokines, whereas IFNs were exclusively induced by TLR3
      stimulation. Here, IL-29 and IL-28A were significantly highly expressed than IFN
      alpha and IFN-beta. TLR3-induced IFN response was enhanced in hepatocytes
      isolated from patients with HCV infection. This hyper-responsiveness could be
      mimicked in naive PHHs consistently stimulated with low dose of poly I:C, but not
      Guardiquimod. The higher responsiveness in PHH isolated from HCV-infected
      patients could be partially explained by higher frequencies of unfavourable SNP
      alleles of different SNPs associated with HCV progression and treatment outcome.
      These data suggest that durable activation of TLR3 but not TLR7, by low doses of
      viral replicative intermediates, increases the sensitivity to viral invasion.
      These findings shed new light on the relevance of TLR3 in the pathogenesis of HCV
      and may provide a possible explanation for the increased ISG expression during
      chronic HCV infection, the so-called IFN paradox.

PMID- 24750365
TI  - Utility of on-site cytological examination and cell block preparation in thyroid
      fine needle aspiration biopsy of metastatic carcinoma: report of two cases.

PMID- 24750364
TI  - Candida arteritis occurring in a liver transplant recipient.
AB  - We report the first case, to our knowledge, of Candida arteritis in a liver
      transplant recipient. The patient presented with hemorrhagic shock requiring
      emergency arterial repair. As Candida albicans, Candida tropicalis, and Candida
      glabrata were growing in the arterial tissue, the patient received antifungal
      therapy for 5 months, but died because of chronic graft dysfunction. No evidence
      of fungal infection was found in the tissue on postmortem examination.

PMID- 24750366
TI  - Long-term evolution, secular trends, and risk factors of renal dysfunction
      following cardiac transplantation.
AB  - Recent reports suggest that individuals who underwent heart transplantation in
      the last decade have improved post-transplant kidney function. The objectives of
      this retrospective study were to describe the incidence and to identify fixed and
      time-dependent predictors of renal dysfunction in cardiac recipients transplanted
      over a 25-year period (1983-2008). To illustrate temporal trends, patients (n =
      306) were divided into five groups based on year of transplantation. The primary
      endpoint was the estimated glomerular filtration rate (eGFR) at year 1. Secondary
      endpoints were time to moderate (eGFR <60 ml/min/1.73 m(2) ) and severe renal
      dysfunction (eGFR <30 ml/min/1.73 m(2) ). Risk factor analyses relied on
      multivariable regression models. Kidney function was mildly impaired before
      transplant (median eGFR=61.0 ml/min/1.73 m(2) ), improved at discharge (eGFR=72.3
      ml/min/1.73 m(2) ; P < 0.001), decreased considerably in the first year (eGFR =
      54.7 ml/min/1.73 m(2) ; P < 0.001), and deteriorated less rapidly thereafter. At
      year 1, 2004-2008 recipients exhibited a higher eGFR compared with all other
      patients (P < 0.001). Factors independently associated with eGFR at year 1 and
      with moderate and severe renal dysfunction included age, gender, pretransplant
      eGFR, blood pressure, glycemia, and use of prednisone (P < 0.05). In summary,
      kidney function worsens constantly up to two decades after cardiac
      transplantation, with the greatest decline occurring in the first year.
      Corticosteroid minimization and treatment of modifiable risk factors
      (hypertension, diabetes) may minimize renal deterioration. 

PMID- 24750367
TI  - Antibodies and antibody-drug conjugates in the treatment of Hodgkin lymphoma.
AB  - Hodgkin lymphoma (HL) is a B cell-derived lymphoid malignancy most often
      affecting young adults. More than 80% of HL patients achieve long-term remission
      after appropriate first-line treatment consisting of multiagent chemotherapy
      and/or radiotherapy (RT). In addition, approximately 50% of patients with disease
      recurrence remain relapse-free after salvage therapy with high-dose chemotherapy
      followed by autologous stem cell transplantation (ASCT). However, patients with
      multiple relapses are mostly in a palliative situation, and novel drugs for this
      patient group are needed. Furthermore, novel less toxic but equally effective
      first-line and second-line approaches are required as therapy-related late
      sequelae represent a relevant cause of morbidity and mortality in HL survivors.
      Several antibodies and antibody-drug conjugates (ADC) targeting CD30 and CD20
      have recently been evaluated in HL. Excellent response rates in heavily
      pretreated patients were observed with the ADC brentuximab vedotin directed
      against CD30. Thus, ongoing trials investigate brentuximab vedotin in different
      additional indications. One example is the first-line treatment of advanced HL
      where the drug is currently being evaluated in combination with variants of the
      first-line protocols ABVD (adriamycin, bleomycin, vinblastine, dacarbazine) and
      escalated BEACOPP (bleomycin, etoposide, adriamycin, cyclophosphamide,
      vincristine, procarbazine, prednisone). Anti-CD20 antibodies given either as
      single agent or in combination with conventional chemotherapy have also been
      investigated and still undergo investigation in prospective studies including HL
      patients. This article reviews the available data on treatment approaches
      including antibodies and ADC in HL patients. 

PMID- 24750368
TI  - Mitochondrial free radical theory of aging: who moved my premise?
AB  - First proposed by D Harman in the 1950s, the Mitochondrial Free Radical Theory of
      Aging (MFRTA) has become one of the most tested and well-known theories in aging
      research. Its core statement is that aging results from the accumulation of
      oxidative damage, which is closely linked with the release of reactive oxygen
      species (ROS) from mitochondria. Although MFRTA has been well acknowledged for
      more than half a century, conflicting evidence is piling up in recent years
      querying the causal effect of ROS in aging. A critical idea thus emerges that
      contrary to their conventional image only as toxic agents, ROS at a non-toxic
      level function as signaling molecules that induce protective defense in responses
      to age-dependent damage. Furthermore, the peroxisome, another organelle in
      eukaryotic cells, might have a say in longevity modulation. Peroxisomes and
      mitochondria are two organelles closely related to each other, and their
      interaction has major implications for the regulation of aging. The present
      review particularizes the questionable sequiturs of the MFRTA, and recommends
      peroxisome, similarly as mitochondrion, as a possible candidate for the
      regulation of aging.

PMID- 24750369
TI  - Adverse reaction to silicone simulating orofacial granulomatosis.
AB  - BACKGROUND: Granulomatous reactions to silicone facial fillers are well described
      in the literature. Clinically, these reactions present as nodules or pseudotumors
      that are frequently described as silicone granulomas or siliconomas. OBJECTIVE:
      We want to report a peculiar form of granulomatous reaction to injected silicone
      characterized by recurrent episodes of facial edema. METHODS: We collected
      silicone infiltrated patients with a similar clinical picture consisting of
      asymptomatic episodes of unilateral facial edema that had been recurring for
      months or years. RESULTS: We found four women with recurrent episodes of facial
      edema. They had been infiltrated with silicone in the face. Histology showed
      silicone deposits and a granulomatous infiltrate in all 4 cases. CONCLUSION: We
      describe and illustrate a new type of adverse reaction to injected silicone
      simulating orofacial granulomatosis. The reaction presents as recurrent,
      unilateral, asymmetric facial edema of the cheek in patients who have been
      injected with silicone in the face. Familiarity with this adverse reaction will
      help to prevent erroneous diagnoses such as idiopathic angioedema, Melkersson
      Rosenthal syndrome, and orofacial granulomatosis.

PMID- 24750370
TI  - Genetic structure of populations of whale sharks among ocean basins and evidence
      for their historic rise and recent decline.
AB  - This study presents genetic evidence that whale sharks, Rhincodon typus, are
      comprised of at least two populations that rarely mix and is the first to
      document a population expansion. Relatively high genetic structure is found when
      comparing sharks from the Gulf of Mexico with sharks from the Indo-Pacific. If
      mixing occurs between the Indian and Atlantic Oceans, it is not sufficient to
      counter genetic drift. This suggests whale sharks are not all part of a single
      global metapopulation. The significant population expansion we found was
      indicated by both microsatellite and mitochondrial DNA. The expansion may have
      happened during the Holocene, when tropical species could expand their range due
      to sea-level rise, eliminating dispersal barriers and increasing plankton
      productivity. However, the historic trend of population increase may have
      reversed recently. Declines in genetic diversity are found for 6 consecutive
      years at Ningaloo Reef in Australia. The declines in genetic diversity being seen
      now in Australia may be due to commercial-scale harvesting of whale sharks and
      collision with boats in past decades in other countries in the Indo-Pacific. The
      study findings have implications for models of population connectivity for whale
      sharks and advocate for continued focus on effective protection of the world's
      largest fish at multiple spatial scales. 

PMID- 24750371
TI  - Safety and efficacy of preoperative autologous blood donation for high-risk
      pregnant women: experience of a large university hospital in Japan.
AB  - AIM: Preoperative autologous blood donation (PAD) has the advantages over
      allogeneic blood transfusion of theoretically no risk of viral infection and
      alloimmunization. However, there are some concerns regarding PAD in pregnant
      women, as they sometimes become anemic and adverse effects such as low blood
      pressure could be harmful to fetuses. In our hospital, the PAD program was
      implemented in 2006 and has been used in pregnant women at high risk of massive
      hemorrhage. In this study, the safety of PAD in pregnant women and its efficacy
      for avoiding allogeneic blood transfusion were investigated. METHODS: The
      hospital records of pregnant women who delivered at our hospital from January
      2009 to June 2012 were reviewed and those who were enrolled in the PAD program
      for predicted massive hemorrhage were analyzed. RESULTS: Among the total of 3095
      deliveries, 69 cases enrolled in the PAD program were analyzed. Blood donation
      was performed 189 times for the 69 cases. The median donated blood volume was
      1200 mL (range, 400-2000). The mean blood loss during delivery was 1976 +/- 1654
      mL. Autologous blood was transfused in 64 cases. Allogeneic blood transfusion was
      required in five cases of massive blood loss exceeding 5000 mL. In the other 64
      cases, no additional allogeneic blood transfusion was required. No adverse events
      were observed in either the pregnant women or fetuses. CONCLUSION: For pregnant
      women at a high risk of massive hemorrhage, our PAD program was safe and
      effective for avoiding allogeneic blood transfusion.

PMID- 24750372
TI  - Post-herpes zoster sarcoidosis.

PMID- 24750373
TI  - Racial disparities in cardiovascular risk factor control in an underinsured
      population with Type 2 diabetes.
AB  - AIM: To investigate the race-specific trend in attainment of the American
      Diabetes Association cardiovascular risk factor control goals (HbA1c <53 mmol/mol
      (7.0%), blood pressure <130/80 mmHg and LDL cholesterol <2.6mmol/l) by patients
      with Type 2 diabetes. METHODS: The study sample included 14 946 African-American
      and 12 758 white patients who were newly diagnosed with Type 2 diabetes between
      2001 and 2009 in the Louisiana State University Hospital system. The race
      specific percentages of patients' attainment of American Diabetes Association
      goals were calculated using the baseline and follow-up measurements of HbA1c ,
      blood pressure, and LDL cholesterol levels. Logistic regression was used to test
      the difference between African-American and white patients. RESULTS: The
      percentage of patients who met all three American Diabetes Association goals
      increased from 8.2% in 2001 to 10.2% in 2009 (increased by 24.4%) in this cohort.
      Compared with African-American patients, white patients had better attainment of
      the following American Diabetes Association goals: HbA1c (61.4 vs. 55.1%), blood
      pressure (25.8 vs. 20.4%), LDL cholesterol (40.1 vs. 37.7%) and all three goals
      (7.3 vs. 5.1%). African-American and white patients generally had a better
      cardiovascular disease risk factor profile during follow-up when we assessed
      attainment of the American Diabetes Association goals by means of HbA1c , blood
      pressure and LDL cholesterol. CONCLUSIONS: During 2001-2009, the present low
      income cohort of people with Type 2 diabetes generally experienced improved
      control of cardiovascular disease risk factors. White patients had better
      attainment of the American Diabetes Association cardiovascular risk factor
      control goals than their African-American counterparts.

PMID- 24750375
TI  - Iris melanocytic nevus with rosettes.

PMID- 24750374
TI  - Electrochemical corrosion and surface analyses of a ni-cr alloy in bleaching
      agents.
AB  - PURPOSE: The aim of this study was to evaluate the corrosion behavior of a Ni-Cr
      dental casting alloy subjected to 10% hydrogen peroxide (HP) and 10% carbamide
      peroxide (CP) bleaching solutions and to determine the composition of the surface
      oxide layer formed on the alloy specimens. MATERIALS AND METHODS: Ten cylindrical
      specimens (4 mm in diameter * 25 mm in height) were cast from a Ni-Cr alloy
      (Wiron 99) and divided into two groups (n = 5). A potentiodynamic polarization
      test was used to compare the corrosion rates of specimens in HP and CP (pH =
      6.5). Before cyclic polarization tests, all alloy specimens were allowed to reach
      a steady open circuit potential (Ecorr ) for a period of 1 hour. Then tests were
      initiated at 100 mV versus standard calomel electrode (SCE) below Ecorr and
      scanned at a rate of 1 mV/s in the anodic direction until reaching 1000 mV over
      the Ecorr value. The scan then was reversed back to the Ecorr of the specimens.
      The open circuit potentials (Ecorr ) and the current densities (Icorr ) were
      determined using the anodic Tafel regions extrapolating from the curves.
      Differences in Ecorr and Icorr were determined using one-way ANOVA (alpha =
      0.05). In addition, corrosion rates were calculated from these curves. Before and
      after polarization tests, a scanning electron microscope (SEM) examination
      accompanied by energy dispersive X-ray spectroscopy (EDS) was used to analyze the
      surface morphology. The surface characterization of the passive film formed on
      alloy specimens was also performed by using X-ray photoelectron spectroscopy
      (XPS). RESULTS: In this study, bleaching agents had an effect on the anodic
      process for two groups. Although no statistical difference was identified between
      the groups for both corrosion parameters, results indicated that the effect of CP
      on the corrosion behavior was less than that of HP. These results agreed with the
      SEM observations. XPS data showed that oxide layers formed on all groups
      contained mainly Cr2 O3 , NiO, and MoO3 , and the amounts of oxides formed on CP
      treated specimens were higher than HP treated ones. Also, molybdenum rates were
      increased with CP application compared to HP. CONCLUSIONS: The comparison of the
      effects of the two bleaching agents at 10% showed that the alloy suffered less
      corrosion with CP than HP. This result was also confirmed by the SEM and XPS
      data. The presence of Mo on the oxide layer affected the oxide layer, leading to
      lower corrosion rates.

PMID- 24750376
TI  - Histological diagnosis of interstitial lung diseases by cryo-transbronchial
      biopsy.
AB  - BACKGROUND AND OBJECTIVE: The gold standard for the histological diagnosis of
      interstitial lung diseases (ILD) is an open lung biopsy (OLB). Tissue samples
      obtained by forceps transbronchial lung biopsies (TBB) are usually too small. We
      aim to evaluate the efficacy and safety of cryo-TBB for the diagnosis of ILD and
      to explore its role as substitute for OLB. METHODS: Seventy-five patients (mean
      age 56.2 years) with clinical and radiological features suggestive of ILD
      underwent cryo-TBB under moderate sedation. The diagnostic contribution on the
      work-up of suspected ILD was assessed. RESULTS: No major complications occurred
      during cryo-TBB procedures. The mean cross-sectional area of the biopsy specimen
      obtained was 9 mm2 with an average of 70% alveolated tissue. The most common
      pathological diagnoses were idiopathic nonspecific interstitial pneumonitis (n =
      22), cryptogenic organizing pneumonia (n = 11) and usual interstitial pneumonitis
      (n = 7). There were three patients of pulmonary Langerhans cell histiocytosis and
      one patient of pulmonary lymphangioleiomyomatosis. A definite and probable
      clinicopathological consensus diagnosis was possible in 70% and 28% of patients,
      respectively. In only 2% of patients' diagnosis could not be established.
      CONCLUSIONS: Cryo-TBB is a safe and effective minimally invasive modality for the
      diagnosis of ILD. No OLB is needed in the majority of patients.

PMID- 24750377
TI  - Use of a birth plan within woman-held maternity records: a qualitative study with
      women and staff in northeast Scotland.
AB  - BACKGROUND: Birth plans are written preferences for labor and birth which women
      prepare in advance. Most studies have examined them as a novel intervention or
      "outside" formal care provision. This study considered use of a standard birth
      plan section within a national, woman-held maternity record. METHODS: Exploratory
      qualitative interviews were conducted with women (42) and maternity service staff
      (24) in northeast Scotland. Data were analyzed thematically. RESULTS: Staff and
      women were generally positive about the provision of the birth plan section
      within the record. Perceived benefits included the opportunity to highlight
      preferences, enhance communication, stimulate discussions, and address anxieties.
      However, not all women experienced these benefits or understood the birth plan's
      purpose. Some were unaware of the opportunity to complete it or could not access
      the support they needed from staff to discuss or be confident about their
      options. Some were reluctant to plan too much. Staff recognized the need to
      support women with birth plan completion but noted practical challenges to this.
      CONCLUSIONS: A supportive antenatal opportunity to allow discussion of options
      may be needed to realize the potential benefits of routine inclusion of birth
      plans in maternity notes.

PMID- 24750378
TI  - Travel-related infection in European travelers, EuroTravNet 2011.
AB  - BACKGROUND: Limited data exist on infectious diseases imported to various
      locations in Europe, particularly after travel within the continent. METHODS: To
      investigate travel-related disease relevant to Europe that is potentially
      preventable through pre-travel intervention, we analyzed the EuroTravNet database
      of 5,965 ill travelers reported by 16 centers in "Western" Europe in 2011.
      RESULTS: There were 54 cases of vaccine-preventable disease, mostly hepatitis A
      (n = 16), typhoid fever (n = 11), and measles (n = 8); 6 cases (including 3
      measles cases) were associated with travel within "Western" Europe. Malaria was
      the most commonly diagnosed infection (n = 482, 8.1% of all travel-related
      morbidity). Among patients with malaria, the military most commonly received pre
      travel advice (95%), followed by travelers for missionary, volunteer, research,
      or aid work (81%) but travelers visiting friends and relatives (VFRs) were least
      likely to receive pre-travel advice (21%). The vast majority (96%) of malaria
      patients were resident in "Western" Europe, but over half (56%) were born
      elsewhere. Other significant causes of morbidity, which could be reduced through
      advice and behavioral change, include Giardia (n = 221, 3.7%), dengue (n = 146,
      2.4%), and schistosomiasis (n = 131, 2.2%). Of 206 (3.5%) travelers with exposure
      in "Western" Europe, 75% were tourists; the highest burden of disease was acute
      gastrointestinal infection (35% cases). Travel from "Eastern" Europe (n = 132,
      2.2%) was largely associated with migration-related travel (53%); among chronic
      infectious diseases, tuberculosis was frequently diagnosed (n = 20). Travelers
      VFRs contributed the largest group of malaria patients (46%), but also had the
      lowest documented rate of pre-travel health advice in this subset (20%). Overall,
      44% of nonimmigrant ill travelers did not receive pre-travel advice. CONCLUSION:
      There is a burden of infectious diseases in travelers attending European health
      centers that is potentially preventable through comprehensive pre-travel advice,
      chemoprophylaxis, and vaccination. Targeted interventions for high-risk groups
      such as travelers VFRs and migration-associated travelers are of particular
      importance.

PMID- 24750379
TI  - Do nonsteroidal anti-inflammatory drugs affect the outcome of arthroscopic
      Bankart repair?
AB  - To achieve pain control after arthroscopic shoulder surgery, nonsteroidal anti
      inflammatory drugs (NSAIDs) are a complement to other analgesics. However,
      experimental studies have raised concerns that these drugs may have a detrimental
      effect on soft tissue-to-bone healing and, thus, have a negative effect on the
      outcome. We wanted to investigate if there are any differences in the clinical
      outcome after the arthroscopic Bankart procedure for patients who received NSAIDs
      prescription compared with those who did not. 477 patients with a primary
      arthroscopic Bankart procedure were identified in the Norwegian shoulder
      instability register and included in the study. 32.5% received prescription of
      NSAIDs post-operatively. 370 (78%) of the patients answered a follow-up
      questionnaire containing the Western Ontario Shoulder Instability index (WOSI).
      Mean follow-up was 21 months. WOSI at follow-up were 75% in the NSAID group and
      74% in the control group. 12% of the patients in the NSAID group and 14% in the
      control group reported recurrence of instability. The reoperation rate was 5% in
      both groups. There were no statistically significant differences between the
      groups. Prescription of short-term post-operative NSAID treatment in the post
      operative period did not influence on the functional outcome after arthroscopic
      Bankart procedures. 

PMID- 24750380
TI  - CXCL10 levels identify individuals with rapid fibrosis at 12 months post
      transplant for hepatitis C virus and predict treatment response.
AB  - BACKGROUNDS: Recurrent hepatitis C virus (HCV) infection is universal post
      transplantation. Fibrosis (F) stage >=2 at 12 months identifies patients with
      rapid fibrosis progression. Antiviral therapy (AVT) remains the only option to
      attenuate fibrosis progression. We hypothesized that CXCL10 levels can
      distinguish between slow and fast fibrosis progression at 12 months, development
      of F >= 4 post-transplantation, and help predict treatment response in patients
      undergoing AVT. METHODS: All patients that had undergone primary liver
      transplantation at King's College Hospital, London, between 2000 and 2011 were
      identified. Quantification of CXCL10 was performed using an ELISA-based assay on
      stored plasma at six months post-transplant and pre-treatment. Comparison was
      made with liver biopsies performed at 12 months and in the post-transplant period
      where available. RESULTS: One hundred and thirty-three patients were included.
      CXCL10 levels were lower in the slow fibrosis group compared to the rapid
      fibrosis group (p < 0.0001). CXCL10 correlated with F stage, necro-inflammatory
      score, and serum transaminases (<0.0001). CXCL10 was an independent predictor of
      F >= 2 at 12 months and F >= 4 (p < 0.05). Pre-treatment CXCL10 levels were an
      independent predictor of sustained virologic response (p = 0.04). CONCLUSIONS:
      CXCL10 levels help identify patients with rapid fibrosis progression in patients
      with recurrent HCV and those that are likely to respond to AVT.

PMID- 24750381
TI  - Chicken egg yolk immunoglobulin (IgY) developed against fusion protein LTB-STa
      STb neutralizes the toxicity of Escherichia coli heat-stable enterotoxins.
AB  - AIM: To obtain a recombinant enterotoxigenic Escherichia coli (ETEC) fusion
      enterotoxin protein LTB-STa-STb (Bab) that can express the immunogenicity of the
      haptens STa and STb and induce their corresponding neutralizing antibodies.
      METHODS AND RESULTS: The three important ETEC enterotoxin genes coding LTB, STa
      and STb were PCR-amplified, and the amplified products were fused to construct
      the trivalent enterotoxin expression vector pET30-Bab. SDS-PAGE and Western blot
      were used to verify the expression of the fusion protein Bab by E. coli BL21
      carrying plasmid pET30-Bab. Laying hens immunized with Bab developed high egg
      yolk immunoglobulin (IgY) titres specific to LTB, STa and STb, and all were
      significantly higher than those in the control group (P < 0.01). A suckling mouse
      assay showed that anti-Bab IgY can neutralize the natural toxicity of STa and STb
      with the highest dilution of 1/2 and 1/32, respectively. CONCLUSIONS: Genetically
      constructed Bab induced significant antibody responses against STa and STb in
      chickens, and the resulting IgY had the capacity to neutralize the toxicity of
      ST. SIGNIFICANCE AND IMPACT OF THE STUDY: The recombinant Bab protein containing
      three important ETEC enterotoxins may serve as an effective and convenient
      polyvalent toxoid that can be used to produce multiple antitoxin IgYs to prevent
      colibacillosis caused by ETEC with various fimbriae in young animals.

PMID- 24750382
TI  - The usefulness of transient elastography in the assessment of patients with HBeAg
      negative chronic hepatitis B virus infection.
AB  - Histological severity is often mandatory for the management of HBeAg-negative
      chronic HBV patients. We evaluated the performance of transient elastography (TE)
      in this setting. We included 357 untreated HBeAg-negative patients with >= 1
      reliable liver stiffness measurement (LSM-kPa) by TE: 182 inactive carriers with
      HBV-DNA < 2000 (n = 139) or 2000-19 999 IU/mL (n = 43) and 175 patients with
      chronic hepatitis B (CHB). In carriers, HBV-DNA > 2000 and/or LSM > 6.5 were
      considered as biopsy indications. LSMs did not differ between carriers with low
      and high viremia, but were lower in carriers than in patients with CHB (5.8 +/-
      1.7 vs 9.0 +/- 5.6, P < 0.001) offering moderate differentiation between these
      two groups (AUROC: 0.705). LSMs did not change significantly in carriers after 16
      (12-24) months. In carriers with a liver biopsy, Ishak's staging scores were
      similar between cased with low and high viremia but higher in cases with LSM >
      6.5 than <= 6.5 kPa. Moderate fibrosis (stages: 2-3) was detected in 0/10
      carriers with only HBV-DNA > 2000 IU/mL, 2/10 (20%) carriers with only LSM > 6.5
      and 5/10 (50%) carriers with both HBV-DNA > 2000 and LSM > 6.5 (P = 0.009). In
      patients with CHB, LSMs correlated significantly with grading and staging scores
      and offered excellent accuracy for >= moderate, >= severe fibrosis or cirrhosis
      (AUROC >= 0.919-0.950). TE can be helpful for the noninvasive assessment of HBeAg
      negative chronic HBV patients. In conclusion, LSMs offer excellent accuracy for
      fibrosis severity in HBeAg-negative patients with CHB and can identify carriers
      with high risk of moderate fibrosis, which may be present in up to 35% of
      carriers with LSM > 6.5 kPa and 50% of carriers with LSM > 6.5 kPa and HBV-DNA >
      2000 IU/mL.

PMID- 24750383
TI  - MicroRNAs in fruit trees: discovery, diversity and future research directions.
AB  - Since the first description of microRNAs (miRNAs) 20 years ago, the number of
      miRNAs identified in different eukaryotic organisms has exploded, largely due to
      the recent advances in DNA sequencing technologies. Functional studies, mostly
      from model species, have revealed that miRNAs are major post-transcriptional
      regulators of gene expression in eukaryotes. In plants, they are implicated in
      fundamental biological processes, from plant development and morphogenesis, to
      regulation of plant pathogen and abiotic stress responses. Although a substantial
      number of miRNAs have been identified in fruit trees to date, their functions
      remain largely uncharacterised. The present review aims to summarise the progress
      made in miRNA research in fruit trees, focusing specifically on the economically
      important species Prunus persica, Malus domestica, Citrus spp, and Vitis
      vinifera. We also discuss future miRNA research prospects in these plants and
      highlight potential applications of miRNAs in the on-going improvement of fruit
      trees.

PMID- 24750384
TI  - Necrotizing fasciitis of the thigh revealing a Crohn's disease.

PMID- 24750385
TI  - Coalescence 2.0: a multiple branching of recent theoretical developments and
      their applications.
AB  - Population genetics theory has laid the foundations for genomic analyses
      including the recent burst in genome scans for selection and statistical
      inference of past demographic events in many prokaryote, animal and plant
      species. Identifying SNPs under natural selection and underpinning species
      adaptation relies on disentangling the respective contribution of random
      processes (mutation, drift, migration) from that of selection on nucleotide
      variability. Most theory and statistical tests have been developed using the
      Kingman coalescent theory based on the Wright-Fisher population model. However,
      these theoretical models rely on biological and life history assumptions which
      may be violated in many prokaryote, fungal, animal or plant species. Recent
      theoretical developments of the so-called multiple merger coalescent models are
      reviewed here (Lambda-coalescent, beta-coalescent, Bolthausen-Sznitman, Xi
      coalescent). We explain how these new models take into account various pervasive
      ecological and biological characteristics, life history traits or life cycles
      which were not accounted in previous theories such as (i) the skew in offspring
      production typical of marine species, (ii) fast adapting microparasites (virus,
      bacteria and fungi) exhibiting large variation in population sizes during
      epidemics, (iii) the peculiar life cycles of fungi and bacteria alternating
      sexual and asexual cycles and (iv) the high rates of extinction-recolonization in
      spatially structured populations. We finally discuss the relevance of multiple
      merger models for the detection of SNPs under selection in these species, for
      population genomics of very large sample size and advocate to potentially examine
      the conclusion of previous population genetics studies. 

PMID- 24750387
TI  - Going for gold: blood planning for the London 2012 Olympic Games.
AB  - The Olympics is one of the largest sporting events in the world. Major events may
      be complicated by disruption of normal activity and major incidents. Health care
      and transfusion planners should be prepared for both. Previously, transfusion
      contingency planning has focused on seasonal blood shortages and pandemic
      influenzas. This article is the first published account of transfusion
      contingency planning for a major event. We describe the issues encountered and
      the lessons identified during transfusion planning for the London 2012 Olympics.
      Planning was started 18 months in advance and was led by a project team reporting
      to the Executive. Planning was based on three periods of Gamestime. The
      requirements were planned with key stakeholders using normal processes enhanced
      by service developments. Demand planning was based on literature review together
      with computer modelling. The aim was blood-stock sufficiency complimented by a
      high readiness donor panel to minimise waste. Plans were widely communicated and
      table-top exercised. Full transfusion services were maintained during both Games
      with all demands met. The new service improvements and high readiness donors
      worked well. Emergency command and control have been upgraded. Red cell
      concentrate (RCC) stock aged but wastage was not significantly increased. The key
      to success was: early planning, stakeholder engagement, service developments,
      integration of transfusion service planning within the wider health care
      community and conduct within an assurance framework.

PMID- 24750386
TI  - Mechanistic differences between phenotypes of chronic lung allograft dysfunction
      after lung transplantation.
AB  - Distinct phenotypes of chronic lung allograft dysfunction (CLAD) after lung
      transplantation are emerging with lymphocytic bronchiolitis (LB)/azithromycin
      reversible allograft dysfunction (ARAD), classical or fibrotic bronchiolitis
      obliterans syndrome (BOS), and restrictive allograft syndrome (RAS) proposed as
      separate entities. We have additionally identified lung transplant recipients
      with prior LB, demonstrating persistent airway neutrophilia (PAN) despite
      azithromycin treatment. The aim of this study was to evaluate differences in the
      airway microenvironment in different phenotypes of CLAD. Bronchoalveolar lavage
      (BAL) from recipients identified as stable (control), LB/ARAD, PAN, BOS, and RAS
      were evaluated for differential cell counts and concentrations of IL-1alpha, IL
      1beta, IL-6, IL-8, and TNF-alpha. Primary human bronchial epithelial cells were
      exposed to BAL supernatants from different phenotypes and their viability
      measured. BOS and RAS showed increased BAL neutrophilia but no change in cytokine
      concentrations compared with prediagnosis. In both LB/ARAD and PAN, significant
      increases in IL-1alpha, IL-1beta, and IL-8 were present. BAL IL-6 and TNF-alpha
      concentrations were increased in PAN and only this phenotype demonstrated
      decreased epithelial cell viability after exposure to BAL fluid. This study
      demonstrates clear differences in the airway microenvironment between different
      CLAD phenotypes. Systematic phenotyping of CLAD may help the development of more
      personalized approaches to treatment. 

PMID- 24750389
TI  - Case of trichomycosis axillaris caused by Corynebacterium propinquum.

PMID- 24750388
TI  - Modulation of alpha and gamma oscillations related to retrospectively orienting
      attention within working memory.
AB  - Selective attention mechanisms allow us to focus on information that is relevant
      to the current behavior and, equally important, ignore irrelevant information. An
      influential model proposes that oscillatory neural activity in the alpha band
      serves as an active functional inhibitory mechanism. Recent studies have shown
      that, in the same way that attention can be selectively oriented to bias sensory
      processing in favor of relevant stimuli in perceptual tasks, it is also possible
      to retrospectively orient attention to internal representations held in working
      memory. However, these studies have not explored the associated oscillatory
      phenomena. In the current study, we analysed the patterns of neural oscillatory
      activity recorded with magnetoencephalography while participants performed a
      change detection task, in which a spatial retro-cue was presented during the
      maintenance period, indicating which item or items were relevant for subsequent
      retrieval. Participants benefited from retro-cues in terms of accuracy and
      reaction time. Retro-cues also modulated oscillatory activity in the alpha and
      gamma frequency bands. We observed greater alpha activity in a ventral visual
      region ipsilateral to the attended hemifield, thus supporting its suppressive
      role, i.e., a functional disengagement of task-irrelevant regions. Accompanying
      this modulation, we found an increase in gamma activity contralateral to the
      attended hemifield, which could reflect attentional orienting and selective
      processing. These findings suggest that the oscillatory mechanisms underlying
      attentional orienting to representations held in working memory are similar to
      those engaged when attention is oriented in the perceptual space.

PMID- 24750390
TI  - Frequency of selected single nucleotide polymorphisms influencing the warfarin
      pharmacogenetics in Slovak population.
AB  - OBJECTIVE: Warfarin represents the most commonly prescribed oral anticoagulants,
      which functions as an antagonist of vitamin K, an essential factor of blood
      coagulation cascade. Warfarin has a narrow therapeutic index. An insufficient
      dose can cause failure of antithrombotic effect, and an overdose increases a risk
      of bleeding. It is known that variability in two genes (CYP2C9 and VKORC1) has a
      significant effect on individual response to warfarin dose. These polymorphisms
      influence more than one-third of known warfarin dose effect. Pharmacogenetics of
      warfarin is less affected by polymorphisms in the other genes such as CYP4F2,
      CYP2C19, and GGCX. MATERIAL AND METHODS: The frequency of selected single
      nucleotide polymorphisms including CYP2C9*2 (430C > T), CYP2C9*3 (1075A > C),
      VKORC1*2 (-1639G > A/1173C > T), VKORC1*3 (3730G > A), GGCX (12970C > G, 8016G >
      A), CYP2C19*2 (681G > A), and CYP4F2*3 (1297G > A) was tested in a control group
      consisting of 112 randomly selected individuals by allele-specific real-time PCR,
      restriction fragment length polymorphism, and bidirectional PCR allele-specific
      amplification. RESULTS AND DISCUSSION: The current results were statistically
      evaluated and compared with other populations. The presented results in Slovak
      population which is in Hardy-Weinberg equilibrium were compared with the
      prevalence in different countries. The incidence of selected polymorphisms in
      Slovak population correlates with Caucasians.

PMID- 24750391
TI  - Self-rated health and associated factors among older people living alone in
      Shanghai.
AB  - AIM: Self-rated health is a reliable and important health measure related to
      older people's mortality and quality of life. Few studies regarding the self
      rated health of older people living alone have been carried out in Mainland
      China. The present study aimed to investigate the self-rated health of older
      people living alone in Shanghai and its associated factors. METHODS: A stratified
      random cluster sample of 521 community-dwelling older people living alone in
      Shanghai completed structured questionnaires through face-to-face interviews. The
      data collected included self-rated health, physical health, depression,
      functional ability, physical activity, health services satisfaction, loneliness,
      social support and sociodemographic variables. RESULTS: More than two-fifths of
      the participants (43.2%) reported good self-rated health. Multinomial logistic
      regression analyses found that chronic disease, acute disease, functional
      ability, satisfaction with health services, depression and age were predictors of
      self-rated health. CONCLUSIONS: Identifying factors associated with the self
      rated health of older people living alone could inform the delivery of
      appropriate health and social care interventions to promote older people's
      health.

PMID- 24750392
TI  - Comparison of different aspects of BMI history to identify undiagnosed diabetes
      in Japanese men and women: Toranomon Hospital Health Management Center Study 12
      (TOPICS 12).
AB  - AIMS: To examine current BMI and various aspects of BMI history as pre-screening
      tools for undiagnosed diabetes in Japanese individuals. METHODS: This cross
      sectional study included 16 226 men and 7026 women aged 30-75 years without a
      self-reported history of clinician-diagnosed diabetes. We estimated the
      probability of having undiagnosed diabetes (fasting glucose >= 7.0 mmol/l and/or
      HbA1c >= 48 mmol/mol (>= 6.5%) for the following variables: current BMI, BMI in
      the early 20s (BMI(20y)), lifetime maximum BMI (BMI(max)), change between BMI in
      the early 20s and current BMI (DeltaBMI(20y-cur)), change between BMI in the
      early 20s and maximum BMI (DeltaBMI(20y-max)), and change between lifetime
      maximum and current BMI (DeltaBMI(max-cur)). RESULTS: The prevalence of
      undiagnosed diabetes was 3.3% (771/23252) among participants. BMI(max) ,
      DeltaBMI(20y-max) and current BMI (1-sd increments) were more strongly associated
      with diabetes than the other factors (multivariate odds ratio 1.58 [95% CI 1.47
      1.70] in men and 1.65 [95% CI 1.43-1.90] in women for BMI(max) ; multivariate
      odds ratio 1.47 [95% CI 1.37-1.58] in men and 1.61 [95% CI 1.41-1.84] in women
      for DeltaBMI(20y-max) ; multivariate odds ratio 1.47 [95% CI 1.36-1.58] in men
      and 1.63 [95% CI 1.40-1.89] in women for current BMI). The probability of having
      diabetes was markedly higher in those with both the highest tertile of BMI(max)
      and greatest DeltaBMI(20y-max) ; however, a substantially lower likelihood of
      diabetes was observed among individuals with the lowest and middle tertiles of
      current BMI (< 24.62 kg/m2 in men and < 22.54 kg/m2 in women). CONCLUSIONS:
      Lifetime maximum BMI and BMI changes from early adulthood were strongly
      associated with undiagnosed diabetes. Adding BMI history to people's current BMI
      would improve the identification of individuals with a markedly higher
      probability of having undiagnosed diabetes.

PMID- 24750394
TI  - Changes in liver fibrosis in HIV/HCV-coinfected patients following different
      outcomes with peginterferon plus ribavirin therapy.
AB  - There is scarce information about the impact of antiviral treatment on subsequent
      progression of liver fibrosis in HIV-infected patients with chronic hepatitis C
      who experience different outcomes following peginterferon-ribavirin therapy. We
      conducted a retrospective study of a cohort of HIV/HCV-coinfected patients with
      longitudinal assessment of liver fibrosis using elastometry. Patients were split
      out into four groups according to the prior peginterferon-ribavirin response:
      sustained virological response (SVR), relapse (R), partial response (PR) and null
      response (NR). A group of untreated, coinfected patients was taken as control.
      Significant liver fibrosis progression (sLFP) was defined as a shift from
      baseline Metavir estimates <= F2 to F3-F4, or by >30% increase in liver stiffness
      in patients with baseline F3-F4. Conversely, significant liver fibrosis
      regression (sLFR) was defined as a shift from baseline Metavir estimates F3-F4 to
      <= F2, or by >30% reduction in liver stiffness in patients that kept on F3-F4. A
      total of 498 HIV/HCV-coinfected patients were examined. They were classified as
      follows: 138 (27.7%) SVR, 40 (8%) R, 61 (12.2%) PR, 71 (14.3%) NR and 188 (37.8%)
      naive. After a mean follow-up of 53.3 months, sLFP occurred less frequently in
      patients with SVR (7.2%) compared with R (25%; P = 0.002), PR (23%; P = 0.002),
      NR (29.6%; P < 0.001) and naive (19.7%; P = 0.002). Conversely, sLFR was 26.1% in
      SVR compared with 10% in R (P = 0.03), 14.8% in PR (P = 0.06), 16.9% in NR (P =
      0.07) and 10.6% in naive (P < 0.001). Sustained clearance of serum HCV-RNA
      following a course of antiviral treatment is the major determinant of liver
      fibrosis regression in HIV/HCV-coinfected patients.

PMID- 24750393
TI  - The timing of introduction of pharmaceutical innovations in seven European
      countries.
AB  - RATIONALE, AIMS AND OBJECTIVES: Differences in the performance of medical care
      may be due to variation in the introduction and diffusion of medical innovations.
      The objective of this paper is to compare seven European countries (United
      Kingdom, the Netherlands, West Germany, France, Spain, Estonia and Sweden) with
      regard to the year of introduction of six specific pharmaceutical innovations
      (antiretroviral drugs, cimetidine, tamoxifen, cisplatin, oxalaplatin and
      cyclosporin) that may have had important population health impacts. METHODS: We
      collected information on introduction and further diffusion of drugs using
      searches in the national and international literature, and questionnaires to
      national informants. We combined various sources of information, both official
      years of registration and other indicators of introduction (clinical trials,
      guidelines, evaluation reports, sales statistics). RESULTS AND CONCLUSIONS: The
      total length of the period between first and last introduction varied between 8
      years for antiretroviral drugs and 22 years for cisplatin. Introduction in
      Estonia was generally delayed until the 1990s. The average time lags were
      smallest in France (2.2 years), United Kingdom (2.8 years) and the Netherlands
      (3.5 years). Similar rank orders were seen for year of registration suggesting
      that introduction lags are not only explained by differences in the process of
      registration. We discuss possible reasons for these between-country differences
      and implications for the evaluation of medical care.

PMID- 24750395
TI  - The histopathologic changes in keratoacanthoma depend on its stage.

PMID- 24750396
TI  - Genital infection caused by Entamoeba histolytica confirmed by polymerase chain
      reaction analyses.
AB  - Entamoeba histolytica is estimated to infect approximately 1% of the global
      population. In Japan, the prevalence of amebic dysentery has been increasing,
      with more than 800 patients newly diagnosed annually. However, genital infection
      with E. histolytica is uncommon even in endemic areas. We present a case of
      vaginitis caused by E. histolytica. A 50-year-old Japanese woman without history
      of overseas travel presented to a nearby clinic with increased vaginal discharge.
      She had hemorrhagic erosion at the uterine cervix with yellowish vaginal
      discharge, and was referred to our hospital for exclusion of malignancy. Cervical
      cytology revealed periodic acid-Schiff-positive protozoa not aggregating around
      squamous cells, and thus amebic vaginitis was suspected. We performed polymerase
      chain reaction (PCR) analyses and identified E. histolytica. The vaginitis was
      treated with metronidazole, and the disappearance of amebic protozoa was
      confirmed by cytology and PCR. Therefore, it may be important to obtain early
      diagnosis by cervical cytology and PCR. 

PMID- 24750397
TI  - Influence of implant/abutment connection on stress distribution to implant
      surrounding bone: a finite element analysis.
AB  - PURPOSE: The objective of this study was to analyze and compare the stress
      distribution in the cortical and trabecular bone between the internal hexagon and
      the Morse taper systems, both with straight abutments. MATERIALS AND METHODS: Two
      implant systems (Morse taper and internal hexagon connections) were simulated in
      maxillary bone. Loads of 100 N (axial) and 50 N (oblique) in relation to the
      implant axes were applied. The 3D finite element method was used to simulate and
      analyze the present study. The analyzed parameters were ultimate tensile strength
      and Von Mises stress. RESULTS: Both systems presented stresses below the bone
      tissue physiological limit as well as a similar distribution in quantitative
      values, with a higher concentration of tension in the cortical surface near the
      neck of the implant in the two conditions of applied loads, with higher values
      for the internal hexagon system. When the groups were evaluated individually, the
      internal hexagon system showed higher compressive stresses, while in the Morse
      taper system, the highest values were traction. CONCLUSIONS: There was a
      difference in the stress location on the prosthetic components of the systems
      studied; however, it did not influence trabecular bone stress generation.

PMID- 24750398
TI  - Altered lysophosphatidic acid (LPA) receptor expression during hepatic
      regeneration in a mouse model of partial hepatectomy.
AB  - BACKGROUND: Hepatic regeneration requires coordinated signal transduction for
      efficient restoration of functional liver mass. This study sought to determine
      changes in lysophosphatidic acid (LPA) and LPA receptor (LPAR) 1-6 expression in
      regenerating liver following two-thirds partial hepatectomy (PHx). METHODS: Liver
      tissue and blood were collected from male C57BL/6 mice following PHx. Circulating
      LPA was measured by enzyme-linked immunosorbent assay (ELISA) and hepatic LPAR
      mRNA and protein expression were determined. RESULTS: Circulating LPA increased
      72 h after PHx and remained significantly elevated for up to 7 days post-PHx.
      Analysis of LPAR expression after PHx demonstrated significant increases in
      LPAR1, LPAR3 and LPAR6 mRNA and protein in a time-dependent manner for up to 7
      days post-PHx. Conversely, LPAR2, LPAR4 and LPAR5 mRNA were barely detected in
      normal liver and did not significantly change after PHx. Changes in LPAR1
      expression were confined to non-parenchymal cells following PHx. CONCLUSIONS:
      Liver regeneration following PHx is associated with significant changes in
      circulating LPA and hepatic LPAR1, LPAR3 and LPAR6 expression in a time- and cell
      dependent manner. Furthermore, changes in LPA-LPAR post-PHx occur after the first
      round of hepatocyte division is complete.

PMID- 24750399
TI  - Associations between economic hardship and markers of self-management in adults
      with type 2 diabetes: results from Diabetes MILES - Australia.
AB  - OBJECTIVE: A socioeconomic gradient exists in Australia for type 2 diabetes
      mellitus (T2DM). It remains unclear whether economic hardship is associated with
      T2DM self-management behaviours. METHODS: Cross-sectional data from a subset of
      the Diabetes MILES - Australia study were used (n=915). The Economic Hardship
      Questionnaire was used to assess hardship. Outcomes included: healthy eating and
      physical activity (Diabetes Self-Care Inventory - Revised), medication-taking
      behaviour (Medication Adherence Rating Scales) and frequency of self-monitoring
      of blood glucose (SMBG). Regression modelling was used to explore the respective
      relationships. RESULTS: Greater economic hardship was significantly associated
      with sub-optimal medication-taking (Coefficient: -0.86, 95%CI -1.54, -0.18), and
      decreased likelihood of regular physical activity (Odds Ratio: 0.47, 0.29, 0.77).
      However, after adjustments for a range of variables, these relationships did not
      hold. Being employed and higher depression levels were significantly associated
      with less-frequent SMBG, sub-optimal medication-taking and less-regular healthy
      eating. Engaging in physical activity was strongly associated with healthy
      eating. CONCLUSIONS: Employment, older age and depressive symptoms, not economic
      hardship, were commonly associated with diabetes self-management. IMPLICATIONS:
      Work-based interventions that promote T2DM self-management in younger, working
      populations that focus on negative emotions may be beneficial.

PMID- 24750400
TI  - Measuring adequacy of prenatal care: does missing visit information matter?
AB  - BACKGROUND: Kotelchuck's Adequacy of Prenatal Care Utilization (APNCU) Index is
      frequently used to classify levels of prenatal care. In the Finger Lakes Region
      (FLR) of upstate New York, prenatal care visit information late in pregnancy is
      often not documented on the birth certificate. We studied the extent of this
      missing information and its impact on the validity of regional APNCU scores.
      METHODS: We calculated the "weeks between" a mother's last prenatal care visit
      and her infant's date of birth. We adjusted the APNCU algorithm creating the Last
      Visit Adequacy of Prenatal Care (LV-APNC) Index using the last recorded prenatal
      care visit date as the end point of care and the expected number of visits at
      that time. We compared maternal characteristics by care level with each index,
      examining rates of reclassification and number of "weeks between" by birth
      hospital. Stuart-Maxwell, McNemar, chi-square, and t-tests were used to determine
      statistical significance. RESULTS: Based on 58,462 births, the mean "weeks
      between" was 2.8 weeks. Compared with their APNCU Index score, 42.4 percent of
      mothers were reclassified using the LV-APNC Index. Major movement occurred from
      Intermediate (APNCU) to Adequate or Adequate Plus (LV-APNC) leaving the
      Intermediate Care group a more at-risk group of mothers. Those with Adequate or
      Adequate Plus Care (LV-APNC) increased by 31.6 percent, surpassing the Healthy
      People 2020 objective. CONCLUSIONS: In the FLR, missing visit information at the
      end of pregnancy results in an underestimation of mothers' prenatal care. Future
      research is needed to determine the extent of this missing visit information on
      the national level.

PMID- 24750401
TI  - Primary mucinous carcinoma of the skin with in-transit metastasis.

PMID- 24750402
TI  - Bilateral pulmonary vein stenting through an unligated vertical vein in a
      postoperative case of TAPVC.
AB  - We present a case of obstructed supracardiac total anomalous connection (TAPVC)
      where the vertical vein was left open at surgery because of significant pulmonary
      artery hypertension. One month following surgery, the patient developed
      progressive pulmonary venous obstruction at the pulmonary vein-left atrial
      junction bilaterally. The pulmonary veins were stented using a technique where
      the unligated vertical vein was utilized to access left atrium.

PMID- 24750403
TI  - Problems associated with hemodialysis and travel.
AB  - BACKGROUND: While there is a recognized risk of hepatitis C acquisition
      associated with dialysis away from the "home" center, there is little documented
      data on the effect that dialysis while traveling has on the dialysis patient's
      health. This study was designed to examine the incidence of travel within a
      hemodialysis population and to ascertain whether travel was associated with
      morbidity for patients on hemodialysis. METHODS: Travel data were collected
      prospectively over a 6-month period, from April 2009, for all patients receiving
      maintenance hemodialysis across our dialysis centers. Biochemical,
      microbiological, and hematological parameters as well as hepatitis serology and
      antibiotic starts were recorded for 12 weeks prior to and following dialysis away
      from center. RESULTS: A total of 172 individuals traveled on 200 occasions. The
      blood stream infection rate for travelers with a central venous catheter was 0.25
      versus 0.83/1,000 access days (p = 0.038) in the 12 weeks pre-travel versus post
      travel. Parenteral and oral antibiotic starts were both significantly elevated
      post-travel and were mainly instituted for either chest or urinary sepsis. There
      was evidence of raised inflammatory markers and anemia on return to center but no
      evidence of hepatitis B or hepatitis C seroconversion. CONCLUSIONS: Travel and
      dialysis away from a patient's usual hemodialysis unit is a common occurrence but
      is associated with an increased risk of bacterial infection, anemia, and
      inflammatory response. This study provides evidence for the concern that
      hemodialysis away from center is associated with increased morbidity.

PMID- 24750404
TI  - Wnt5a: a potential factor linking psoriasis to metabolic complications.
AB  - Psoriasis is associated with comorbidity including obesity, insulin resistance
      and diabetes mellitus type 2. In obesity, the protein wingless-type MMTV
      integration site Family, Member 5a (wnt5a) is released from adipose tissue
      macrophages and was shown to be of importance in the development of insulin
      resistance. As wnt5a was also shown to be upregulated in psoriatic skin lesions,
      we investigated whether wnt5a and its counterpart secreted frizzled-related
      protein 5 are altered in the circulation of lean and obese patients with
      psoriasis compared with lean and obese healthy volunteers by measuring serum
      concentrations of both proteins. Our results showed that wnt5a was significantly
      higher in lean patients with psoriasis (0.096 ng/ml; SD 0.12) compared with lean
      healthy controls (0.020 ng/ml; SD 0.04; P <= 0.01) as well as in obese patients
      (0.177 ng/ml; SD 0.14) compared with obese healthy controls (0.011 ng/ml; SD
      0.03; P <= 0.001). Therefore, we suggest that in psoriasis, an increase in wnt5a
      may contribute to the development of metabolic comorbidity.

PMID- 24750405
TI  - Effect of salt-tolerant plant growth-promoting rhizobacteria on wheat plants and
      soil health in a saline environment.
AB  - Salt-tolerant plant growth-promoting rhizobacteria (ST-PGPR) significantly
      influence the growth and yield of wheat crops in saline soil. Wheat growth
      improved in pots with inoculation of all nine ST-PGPR (ECe = 4.3 dS.m(-1) ;
      greenhouse experiment), while maximum growth and dry biomass was observed in
      isolate SU18 Arthrobacter sp.; simultaneously, all ST-PGPR improved soil health
      in treated pot soil over controls. In the field experiment, maximum wheat root
      dry weight and shoot biomass was observed after inoculation with SU44 B.
      aquimaris, and SU8 B. aquimaris, respectively, after 60 and 90 days. Isolate SU8
      B. aquimaris, induced significantly higher proline and total soluble sugar
      accumulation in wheat, while isolate SU44 B. aquimaris, resulted in higher
      accumulation of reducing sugars after 60 days. Percentage nitrogen (N), potassium
      (K) and phosphorus (P) in leaves of wheat increased significantly after
      inoculation with ST-PGPR, as compared to un-inoculated plants. Isolate SU47 B.
      subtilis showed maximum reduction of sodium (Na) content in wheat leaves of about
      23% at both 60 and 90 days after sowing, and produced the best yield of around
      17.8% more than the control. 

PMID- 24750406
TI  - Characteristics of Epstein-Barr viraemia in adult liver transplant patients: a
      retrospective cohort study.
AB  - Therapeutic immunosuppression following solid organ transplantation increases the
      risk of Epstein-Barr (EBV) viraemia, which is implicated in post-transplant
      lymphoproliferative disease (PTLD). We retrospectively analysed the incidence of
      EBV viraemia and clinical outcomes in 98 liver transplant recipients. Patients
      underwent EBV DNA monitoring by whole-blood PCR: EBV levels were correlated with
      clinical parameters and outcomes for a median of 249 days. 67% patients developed
      EBV viraemia (EBV DNA >=100 copies/ml) and 30% had sustained viraemia. There was
      a trend towards higher hazard ratios for viraemia with exposure to aciclovir (HR
      1.57, P = 0.12) or in recipients of a poorly HLA-matched graft (HR 1.62, P =
      0.10). These associations became significant in the subgroup with >90 days
      surveillance; HR 2.54 (P = 0.0015) for aciclovir and HR 1.99 (P = 0.03) for
      poorly matched grafts. The converse was true with ganciclovir (HR 0.56 P = 0.13).
      Viraemia was more prolonged in men (median duration 7 days vs 1; P = 0.01) and in
      those with lower UKELD scores (11 days vs 1 day; P = 0.001) but shortened with
      ganciclovir exposure (P = 0.06). Younger patients were more likely to have high
      peak viral loads (P = 0.07). No clinical signs or symptoms or adverse outcomes
      were associated with EBV reactivation. 

PMID- 24750407
TI  - Use of cyclosporin A for successful management of steroid-resistant Sweet's
      syndrome patient with possible myelodysplastic syndrome.

PMID- 24750408
TI  - Topiramate in the management of feline idiopathic ulcerative dermatitis in a two
      year-old cat.
AB  - BACKGROUND: Feline idiopathic ulcerative dermatosis is a rare, poorly understood
      condition characterized by self-trauma. The lesion presents as a nonhealing,
      crusted ulcer, which occurs most commonly on the dorsal midline of the neck or
      between the scapulae. ANIMAL: A 2-year-old female neutered domestic short hair
      cat was presented with an ulcerative dermatosis affecting the dorsal midline.
      Previous investigations had failed to identify the cause, and the lesion was
      resistant to treatment. METHODS AND RESULTS: Diagnosis was based on clinical
      findings and confirmed by histopathology showing epidermal ulceration and
      superficial necrosis with a mild dermal infiltrate together with subepidermal
      fibrosis. The cat had been fed a commercial hypoallergenic diet for 6 months,
      which had successfully managed its chronic diarrhoea. Deep skin scrapings,
      cytology and fungal culture failed to demonstrate pathogens. CONCLUSIONS AND
      CLINICAL IMPORTANCE: Remission was obtained within 4 weeks and has been
      maintained over a 30 month period with topiramate (5 mg/kg orally twice daily),
      an anti-epileptic drug used in human medicine. Attempts to withdraw this therapy
      led to relapse within 24 h on two occasions. To the best of the authors'
      knowledge, this is the first case report of the use of this drug for feline
      idiopathic ulcerative dermatosis.

PMID- 24750409
TI  - Drawing ecological inferences from coincident patterns of population- and
      community-level biodiversity.
AB  - Biodiversity is comprised of genetic and phenotypic variation among individual
      organisms, which might belong to the same species or to different species.
      Spatial patterns of biodiversity are of central interest in ecology and evolution
      for several reasons: to identify general patterns in nature (e.g. species-area
      relationships, latitudinal gradients), to inform conservation priorities (e.g.
      identifying hotspots, prioritizing management efforts) and to draw inferences
      about processes, historical or otherwise (e.g. adaptation, the centre of origin
      of particular clades). There are long traditions in ecology and evolutionary
      biology of examining spatial patterns of biodiversity among species (i.e. in
      multispecies communities) and within species, respectively, and there has been a
      recent surge of interest in studying these two types of pattern simultaneously.
      The idea is that examining both levels of diversity can materially advance the
      above-stated goals and perhaps lead to entirely novel lines of inquiry. Here, we
      review two broad categories of approach to merging studies of inter- and
      intraspecific variation: (i) the study of phenotypic trait variation along
      environmental gradients and (ii) the study of relationships between patterns of
      molecular genetic variation within species and patterns of distribution and
      diversity across species. For the latter, we report a new meta-analysis in which
      we find that correlations between species diversity and genetic diversity are
      generally positive and significantly stronger in studies with discrete sampling
      units (e.g. islands, lakes, forest fragments) than in studies with nondiscrete
      sampling units (e.g. equal-area study plots). For each topic, we summarize the
      current state of knowledge and key future directions. 

PMID- 24750410
TI  - Virological efficacy of combination therapy with corticosteroid and nucleoside
      analogue for severe acute exacerbation of chronic hepatitis B.
AB  - The short-term prognosis of patients with severe acute exacerbation of chronic
      hepatitis B (CHB) leading to acute liver failure is extremely poor. We have
      reported the efficacy of corticosteroid in combination with nucleoside analogue
      in the early stages, but virological efficacy has not been documented. Our aim
      was to elucidate the virological efficacy of this approach. Thirteen patients
      defined as severe acute exacerbation of CHB by our uniform criteria were
      prospectively examined for virological responses to treatment. Nucleoside
      analogue and sufficient dose of corticosteroids were introduced as soon as
      possible after the diagnosis of severe disease. Of the 13 patients, 7 (54%)
      survived, 5 (38%) died and 1 (8%) received liver transplantation. The decline of
      HBV DNA was significant between the first 2 weeks (P = 0.02) and 4 weeks (P <
      0.01). Mean reduction in HBV DNA during the first 2 weeks was 1.7 +/- 0.9 log
      copies per mL in overall patients, 2.1 +/- 0.8 in survived patients and 1.2 +/-
      0.9 in dead/transplanted patients. The decline of HBV DNA was significant between
      the first 2 weeks (P = 0.03) and 4 weeks (P = 0.02) in survived patients, but not
      in dead/transplanted patients. Our study shows that corticosteroid treatment in
      combination with nucleotide analogue has sufficient virological effect against
      severe acute exacerbation of CHB, and a rapid decline of HBV DNA is conspicuous
      in survived patients.

PMID- 24750411
TI  - Household crowding associated with childhood otitis media hospitalisations in New
      Zealand.
AB  - OBJECTIVE: To examine the association between hospitalisations for otitis media
      and area-level measures of household crowding among children in New Zealand.
      METHODS: Counts of hospital admissions for otitis media by census area unit were
      offset against population data from the 2006 national census. Area-level
      household crowding, exposure to tobacco smoke in the home, equivalised income and
      individual-level characteristics age and sex were adjusted for. To examine effect
      modification by ethnicity, three separate poisson models were examined for the
      total, Maori and non-Maori populations. RESULTS: Household crowding was
      significantly associated with hospital admissions for otitis media after
      adjustment in all three models. Neighbourhoods with the highest compared to the
      lowest proportion of crowded homes exhibited incidence rate ratios of 1.25 (95%CI
      1.12-1.37) in the total population, 1.59 (95%CI 1.21-2.04) in the Maori
      restricted model and 1.17 (95%CI 1.06-1.32) in the non-Maori restricted model.
      CONCLUSIONS: Otitis media hospitalisations are associated with area-level
      measures of household crowding and other risk factors in this ecological study.
      The largest increase in otitis media incidence relative to neighbourhood rates of
      household crowding was exhibited among Maori cases of otitis media. IMPLICATIONS:
      This study adds weight to the growing body of literature linking infectious
      disease risk to overcrowding in the home.

PMID- 24750412
TI  - A novel G6PC3 gene mutation in severe congenital neutropenia: pancytopenia and
      variable bone marrow phenotype can also be part of this syndrome.
AB  - Glucose-6-phosphatase catalytic subunit 3 (G6PC3) deficiency is a newly described
      syndrome characterized by severe congenital neutropenia associated with multiple
      organ abnormalities including cardiac and urogenital malformations. The
      underlying pathophysiology of increased apoptosis of myeloid cells and of
      neutrophil dysfunction in G6PC3 deficiency involves disturbed glucose metabolism,
      increased endoplasmic reticulum stress and deficient protein folding. Here, we
      report a new case of G6PC3 deficiency caused by a novel homozygous G6PC3 gene
      mutation p.Trp59Arg. The patient showed pancytopenia and a variable bone marrow
      phenotype with maturation arrest and vacuolization in myeloid lineage cells and a
      normocellular marrow, respectively. She also showed persistent lymphopenia with
      low CD4 T- and CD19 B-cell counts. Lymphopenia and even pancytopenia as well as a
      variable bone marrow phenotype can be part of this syndrome. These clinical
      findings in a patient with chronic neutropenia should alert the clinician to
      consider a diagnosis of G6PC3 deficiency. 

PMID- 24750413
TI  - Management of squamous cell vulvar cancer: a review.
AB  - Squamous cell vulvar cancer is a rare gynecologic malignancy. Standard treatment
      for early stage disease consists of wide radical excision of the primary tumor
      with inguinal-femoral lymphadenectomy or sentinel lymph node mapping/biopsy.
      Because of the general paucity of patients with advanced vulvar cancer, there is
      no standard therapy for advanced disease and therefore treatment should be
      individualized. Intergroup trials are needed to clarify the value of
      chemoradiation, neoadjuvant chemotherapy and targeted therapy in patients with
      advanced squamous cell cancer of the vulva to identify modalities with the best
      therapeutic index and lowest morbidity. 

PMID- 24750414
TI  - Combined pancreaticoduodenectomy and colon resection for locally advanced peri
      ampullary tumours: analysis of peri-operative morbidity and mortality.
AB  - BACKGROUND: Combined pancreaticoduodenectomy (PD) and colonic resection may be
      necessary to achieve an R0 resection of peri-ampullary tumours. The aim of this
      study was to examine the morbidity and mortality associated with this procedure.
      METHODS: A retrospective cohort study was performed comparing 607 patients who
      underwent a standard pancreaticoduodenectomy (S-PD) to 28 patients who had a
      concomitant colon resection and PD (PD-colon) over a 10-year period at an
      academic centre. RESULTS: Patients in the PD-colon group were more likely to have
      received neoadjuvant chemotherapy +/- radiation (3/28, 11% versus 14/607, 2%, P =
      0.024). Operative time was also longer (530 versus 410 min, P < 0.001) and they
      were more likely to have had portal vein resections (9/28, 32% versus 76/607,
      13%, P = 0.007). There was no difference in the intra-operative blood loss,
      length of stay, or overall complication rates. The PD-colon group had a higher
      rate of severe post-operative bleeding (4/28, 11% versus 8/607, 1%, P = 0.002).
      The post-operative mortality rates for the PD-colon and PD groups were 2/28 (7%)
      and 8/607 (1%), respectively (P = 0.068). CONCLUSIONS: PD-colon has an acceptable
      risk of peri-operative morbidity compared with S-PD in well-selected patients.

PMID- 24750415
TI  - Pemphigus vulgaris of the epiglottis successfully treated with rituximab.

PMID- 24750416
TI  - Effect of beverages and mouthwashes on the hardness of polymers used in intraoral
      prostheses.
AB  - PURPOSE: The mechanical properties of acrylic resins used in intraoral prostheses
      may be altered by frequent exposure to liquids such as beverages and mouthwashes.
      This study aimed to evaluate the effect of thermocycling and liquid immersion on
      the hardness of four brands of acrylic resins commonly used in removable
      prostheses (Onda Cryl, QC-20, Classico, Lucitone). MATERIALS AND METHODS: For
      each brand of resin, seven specimens were immersed in each of six solutions
      (coffee, cola, red wine, Plax-Colgate, Listerine [LI], Oral B), and seven more
      were placed in artificial saliva (control). The hardness was tested using a
      microhardness tester before and after 5000 thermocycles and after 1, 3, 24, 48,
      and 96 hours of immersion. The results were analyzed using three-way repeated
      measures ANOVA and Tukey's test (p < 0.05). RESULTS: The hardness of the resins
      decreased following thermocycling and immersion in the solutions. Specimens
      immersed in cola and wine exhibited significant decreases in hardness after
      immersion for 96 hours, although the greatest significant decrease in hardness
      occurred in specimens immersed in LI. However, according to American Dental
      Association specification 12, the Knoop hardness of acrylic resins for intraoral
      prostheses should not be below 15. Thus, the median values of superficial
      hardness observed in most of the acrylic resins in this study are considered
      clinically acceptable. CONCLUSIONS: The microhardness of polymers used for
      intraoral prostheses decreases following thermocycling. Among specimens immersed
      in beverages, those immersed in cola or wine experienced the greatest decrease in
      microhardness. Immersion of acrylic resins in LI significantly decreased the
      microhardness in relation to the initial value. Among the resins assessed, QC-20
      exhibited the lowest initial hardness.

PMID- 24750417
TI  - The licence for a custom-made medicinal product is an adaptive licence.

PMID- 24750418
TI  - Integrated evaluation of scrotal temperature and testosteronemia after GnRH
      administration in young bulls with low semen production.
AB  - The aim of this study was to determine the suitability of thermographic
      monitoring of scrotal surface temperature (SST) as a method to monitor testicular
      function. Yearling bulls (n = 23) with low semen production were selected.
      Scrotal surface temperature and serum testosterone (T) concentrations were
      evaluated before and after administration of 10.5 MUg buserelin acetate IV.
      Thermographic images of scrotum were recorded at 0, 15, 30, 45 and 60 min post
      GnRH, while blood sampling was only performed at 60 min post-GnRH. Bulls were
      divided in two groups: LowTemp bulls (n = 10) had a decreased SST at 60 min;
      HighTemp bulls (n = 13) had an increased SST. After 60 min, LowTemp bulls had
      higher T concentrations compared to HighTemp bulls: 14.32 ng/ml +/- 0.53 vs 10.30
      +/- 1.37 ng/ml (mean +/- SEM; p < 0.05), respectively. Reproductive performances
      in both groups improved after GnRH administration, resulting in an increased
      number of inseminating doses from each collection, which was higher in LowTemp
      bulls. Pearson correlation test showed a negative relationship between T and SST
      (r = -0.554). In conclusion, a decreased scrotal surface temperature 60 min after
      GnRH treatment was associated with improved semen production. 

PMID- 24750419
TI  - The effectiveness of weight management interventions in breastfeeding women--a
      systematic review and critical evaluation.
AB  - BACKGROUND: The postpartum period is a vulnerable time for excess weight
      retention, particularly for the increasing number of women who are overweight at
      the start of their pregnancy and subsequently find it difficult to lose
      additional weight gained during pregnancy. Although postpartum weight management
      interventions play an important role in breaking this potentially vicious cycle
      of weight gain, the effectiveness of such interventions in breastfeeding women
      remains unclear. Our aim was to systematically review the literature about the
      effectiveness of weight management interventions in breastfeeding women. METHODS:
      Seven electronic databases were searched for eligible papers. Intervention
      studies included were carried out exclusively in breastfeeding mothers, <=2 years
      postpartum and with a body mass index greater than 18.5 kg/m(2) , with an outcome
      measure of change in weight and/or body composition. RESULTS: Six studies met the
      selection criteria, and were stratified according to the type of intervention and
      outcome measures. Despite considerable heterogeneity among studies, the dietary
      based intervention studies appeared to be the most efficacious in promoting
      weight loss; however, few studies were tailored toward the needs of breastfeeding
      women. CONCLUSIONS: Weight management interventions which include an energy
      restricted diet may play a key role in successful postpartum weight loss for
      breastfeeding mothers.

PMID- 24750420
TI  - Entero-Behcet's disease coexisting with long-term epilepsy and schizophrenia-like
      symptoms.
AB  - Entero-Behcet's disease coexisting with long-term epilepsy and schizophrenia-like
      symptoms is presented. A 43-year-old woman presented with repeatedly occurring
      aphthous stomatitis for several years. She had been treated for absence seizures,
      epilepsy and schizophrenia since she was 9 years old. She presented with multiple
      aphthous stomatitis on her gingiva, erythema nodosum-like symptoms on the right
      lateral aspect of her leg and genital ulcers on her perianal area. She also
      showed polyarthritis. Laboratory examinations revealed elevated C-reactive
      protein, elevated neutrophil counts, decreased serum Fe and elevated serum Cu.
      Histological examination showed perivascular neutrophil and mononuclear cell
      infiltrates and eosinophilic change of the vessel wall in the lobules of
      subcutaneous fat tissue. Six weeks after the oral prednisolone therapy, she
      showed resolution of aphthous stomatitis, folliculitis-like eruption and genital
      ulcer. She experienced severe abdominal pain after the start of treatment of
      Behcet's disease. Plain computed tomography revealed edematous change in the
      appendix, and ascending and transverse colon. These results led to the diagnosis
      of entero-Behcet's disease acute exaggeration. Treatment with infliximab (300
      mg/once) was started. Eight weeks after the start of infliximab, her abdominal
      pain disappeared and C-reactive protein decreased, followed by the successful
      change to adalimumab infusion therapy. 

PMID- 24750421
TI  - Transportation capacity for patients with highly infectious diseases in Europe: a
      survey in 16 nations.
AB  - Highly infectious diseases (HIDs) are defined as being transmissible from person
      to person, causing life-threatening illnesses and presenting a serious public
      health hazard. In most European Union member states specialized isolation
      facilities are responsible for the management of such cases. Ground ambulances
      are often affiliated with those facilities because rapid relocation of patients
      is most desirable. To date, no pooled data on the accessibility, technical
      specifications and operational procedures for such transport capacities are
      available. During 2009, the 'European Network for HIDs' conducted a cross
      sectional analysis of hospitals responsible for HID patients in Europe including
      an assessment of (a) legal aspects; (b) technical and infrastructure aspects; and
      (c) operational procedures for ground ambulances used for HID transport. Overall,
      48 isolation facilities in 16 European countries were evaluated and feedback
      rates ranged from 78% to 100% (n = 37 to n = 48 centres). Only 46.8% (22/47) of
      all centres have both national and local guidelines regulating HID patient
      transport. If recommended, specific equipment is found in 90% of centres (9/10),
      but standard ambulances in only 6/13 centres (46%). Exclusive entrances (32/45;
      71%) and pathways (30/44; 68.2%) for patient admission, as well as protocols for
      disinfection of ambulances (34/47; 72.3%) and equipment (30/43; 69.8%) exist in
      most centres. In conclusion, the availability and technical specifications of
      ambulances broadly differ, reflecting different preparedness levels within the
      European Union. Hence, regulations for technical specifications and operational
      procedures should be harmonized to promote patient and healthcare worker safety.

PMID- 24750422
TI  - Mental health: outcomes of 10 babies of mothers with a history of serious mental
      illness.
AB  - Women with serious mental illness are frequently on antipsychotic medications to
      maintain their mental health. During pregnancy there is much debate as to whether
      to continue or cease these medications. The possibility of adverse effects is of
      concern to clinicians and the women. This study used a case study methodology to
      identify the outcomes for 10 babies of women with a history of serious mental
      illness. The results provide further evidence in regard to women and the use of
      antipsychotic medications throughout pregnancy and during the first year after
      birth. Separation of mother and baby occurred in five of the 10 babies. This
      study identifies the neonatal complications for these vulnerable babies as not
      outside the norm for births in Australia. The high rate of mother-baby separation
      is of great concern and needs further longitudinal studies.

PMID- 24750423
TI  - Frequency and significance of IgG4 immunohistochemical staining in liver explants
      from patients with primary sclerosing cholangitis.
AB  - Dense tissue infiltrates of IgG4(+) plasma cells >50/high-powered field (HPF) are
      purportedly highly specific for IgG4-related disease. However, the frequency and
      significance of liver-infiltrating IgG4(+) plasma cells in primary sclerosing
      cholangitis (PSC) applying these cut-offs has not been determined. We sought to
      determine the incidence of intrahepatic IgG4-positive staining in PSC patients
      undergoing transplantation, correlating findings with clinical parameters.
      Immunohistochemical staining was performed on liver explants obtained between
      1991 and 2009. Of 122 explants obtained, hilar IgG4(+) staining was found to be
      mild (10-29 IgG4(+) cells/HPF) in 23.0%, moderate (30-50/HPF) in 9.0% and marked
      (>50/HPF) in 15.6%. Marked hilar lymphoplasmacytic infiltration was significantly
      associated with marked hilar IgG4(+) staining (P < 0.001). No patient had marked
      peripheral IgG4(+) staining, although mild and moderate staining was observed in
      24.5% and 3.3% respectively. Marked hilar IgG4(+) staining was significantly
      associated with the presence of dominant biliary strictures (P = 0.01) and need
      for biliary stenting (P = 0.001). There did not, however, exist any significant
      differences in the age at PSC diagnosis, presence of inflammatory bowel disease
      or extrahepatic autoimmune disease, frequency of cholangiocarcinoma, interval
      between diagnosis and transplantation, or post-transplant PSC recurrence or
      survival. Of 51 control liver sections (PBC = 18; HCV = 19; HBV = 8; AIH = 6),
      none had marked or moderate hilar IgG4(+) staining, whereas mild staining was
      seen in only 10% (P < 0.001). Marked (>50/HPF) hilar IgG4(+) lymphoplasmacytic
      infiltration is frequently observed in PSC and associated with the presence of
      dominant biliary strictures. However, unlike serum IgG4(+) , this does not
      seemingly associate with clinical disease course. 

PMID- 24750424
TI  - Alternative for surgical management of calcific aortic valve stenosis: sutureless
      valve implants.
AB  - Patients who are candidates for surgical valve replacement (AVR) may benefit from
      diminished length of cardiopulmonary bypass time. Sutureless valve technology for
      AVR may facilitate the performance of the operation through smaller incisions,
      and more expeditiously due to the ability to anchor traditional bovine
      pericardial prostheses without the need for sutures. We report the first
      successful US implants of the Sorin PERCEVAL valve as part of the FDA IDE trial.

PMID- 24750425
TI  - Molecular cytogenetic characterisation and phylogenetic analysis of the seven
      cultivated Vigna species (Fabaceae).
AB  - The genomic organisation of the seven cultivated Vigna species, V. unguiculata,
      V. subterranea, V. angularis, V. umbellata, V. radiata, V. mungo and V.
      aconitifolia, was determined using sequential combined PI and DAPI (CPD) staining
      and dual-colour fluorescence in situ hybridisation (FISH) with 5S and 45S rDNA
      probes. For phylogenetic analyses, comparative genomic in situ hybridisation
      (cGISH) onto somatic chromosomes and sequence analysis of the internal
      transcribed spacer (ITS) of 45S rDNA were used. Quantitative karyotypes were
      established using chromosome measurements, fluorochrome bands and rDNA FISH
      signals. All species had symmetrical karyotypes composed of only metacentric or
      metacentric and submetacentric chromosomes. Distinct heterochromatin
      differentiation was revealed by CPD staining and DAPI counterstaining after FISH.
      The rDNA sites among all species differed in their number, location and size.
      cGISH of V. umbellata genomic DNA to the chromosomes of all species produced
      strong signals in all centromeric regions of V. umbellata and V. angularis, weak
      signals in all pericentromeric regions of V. aconitifolia, and CPD-banded
      proximal regions of V. mungo var. mungo. Molecular phylogenetic trees showed that
      V. angularis and V. umbellata were the closest relatives, and V. mungo and V.
      aconitifolia were relatively closely related; these species formed a group that
      was separated from another group comprising V. radiata, V. unguiculata ssp.
      sesquipedalis and V. subterranea. This result was consistent with the
      phylogenetic relationships inferred from the heterochromatin and cGISH patterns;
      thus, fluorochrome banding and cGISH are efficient tools for the phylogenetic
      analysis of Vigna species. 

PMID- 24750427
TI  - Life history influences how fire affects genetic diversity in two lizard species.
AB  - 'Fire mosaics' are often maintained in landscapes to promote successional
      diversity in vegetation with little understanding of how this will affect
      ecological processes in animal populations such as dispersal, social organization
      and re-establishment. To investigate these processes, we conducted a replicated,
      spatiotemporal landscape genetics study of two Australian woodland lizard species
      [Amphibolurus norrisi (Agamidae) and Ctenotus atlas (Scincidae)]. Agamids have a
      more complex social and territory structure than skinks, so fire might have a
      greater impact on their population structure and thus genetic diversity. Genetic
      diversity increased with time since fire in C. atlas and decreased with time
      since fire in A. norrisi. For C. atlas, this might reflect its increasing
      population size after fire, but we could not detect increased gene flow that
      would reduce the loss of genetic diversity through genetic drift. Using landscape
      resistance analyses, we found no evidence that postfire habitat succession or
      topography affected gene flow in either species and we were unable to distinguish
      between survival and immigration as modes of postfire re-establishment. In A.
      norrisi, we detected female-biased dispersal, likely reflecting its territorial
      social structure and polygynous mating system. The increased genetic diversity in
      A. norrisi in recently burnt habitat might reflect a temporary disruption of its
      territoriality and increased male dispersal, a hypothesis that was supported with
      a simulation experiment. Our results suggest that the effects of disturbance on
      genetic diversity will be stronger for species with territorial social
      organization.

PMID- 24750428
TI  - Delayed-enhancement magnetic resonance imaging could detect the substrate of an
      unusual macroreentrant atrial tachycardia?

PMID- 24750426
TI  - Role of lateral hypothalamus in two aspects of attention in associative learning.
AB  - Orexin (hypocretin) and melanin-concentrating hormone (MCH) neurons are unique to
      the lateral hypothalamic (LH) region, but project throughout the brain. These
      cell groups have been implicated in a variety of functions, including reward
      learning, responses to stimulants, and the modulation of attention, arousal and
      the sleep/wakefulness cycle. Here, we examined roles for LH in two aspects of
      attention in associative learning shown previously to depend on intact function
      in major targets of orexin and MCH neurons. In experiments 1 and 2, unilateral
      orexin-saporin lesions of LH impaired the acquisition of conditioned orienting
      responses (ORs) and bilaterally suppressed FOS expression in the amygdala central
      nucleus (CeA) normally observed in response to food cues that provoke conditioned
      ORs. Those cues also induced greater FOS expression than control cues in LH
      orexin neurons, but not in MCH neurons. In experiment 3, unilateral orexin
      saporin lesions of LH eliminated the cue associability enhancements normally
      produced by the surprising omission of an expected event. The magnitude of that
      impairment was positively correlated with the amount of LH damage and with the
      loss of orexin neurons in particular, but not with the loss of MCH neurons. We
      suggest that the effects of the LH orexin-saporin lesions were mediated by their
      effect on information processing in the CeA, known to be critical to both
      behavioral phenomena examined here. The results imply close relations between LH
      motivational amplification functions and attention, and may inform our
      understanding of disorders in which motivational and attentional impairments co
      occur. 

PMID- 24750429
TI  - Laparoscopic microwave ablation in patients with hepatocellular carcinoma: a
      prospective cohort study.
AB  - OBJECTIVES: There are no prospective studies of laparoscopic microwave (MW)
      ablation in patients with hepatocellular carcinoma (HCC). The aim of this study
      was to demonstrate the safety and efficacy of laparoscopic MW ablation. METHODS:
      A prospective study group of consecutive HCC patients considered ineligible for
      liver resection and/or percutaneous ablation was conducted from December 2009 to
      December 2010. Short-term (3-month) outcomes included a centralized revision of
      radiological response, mortality and morbidity. Mid-term (24-month) outcomes
      included time to recurrence in the study group compared with that in a cohort of
      consecutive patients treated with laparoscopic radiofrequency (RF) ablation using
      propensity score analysis. RESULTS: A total of 42 patients were enrolled. Their
      median age was 64 years; 67% were positive for hepatitis C virus; 33% were of
      Child-Pugh class B status; the median tumour diameter was 2.5 cm, and 48% of
      patients had multinodular HCC. In 47 of 50 (94%) nodules treated with MW
      ablation, a complete radiological response was observed at 3 months. There was no
      perioperative mortality. The overall morbidity rate was 24%. The 2-year survival
      rate was 79% and the 2-year recurrence rate was 55%. Using propensity score
      analysis (in 28 MW ablation patients and 28 RF ablation controls), 2-year
      recurrence rates were 55% in the MW ablation group and 77% in the control group
      (P = 0.03). CONCLUSIONS: Laparoscopic MW ablation is a safe and effective
      therapeutic option for selected HCC patients who are ineligible for liver
      resection and/or percutaneous ablation.

PMID- 24750430
TI  - Relationship between self-reported sleep bruxism and pain in patients with
      temporomandibular disorders.
AB  - The aim of this study was to evaluate the association between self-reported sleep
      bruxism and the age, gender, clinical subtypes of temporomandibular disorders
      (TMD), pain intensity and grade of chronic pain in patients previously diagnosed
      with TMD. Thousand two-hundred and twenty patients of the Andalusian Health
      Service were examined using the Research Diagnostic Criteria for
      Temporomandibular Disorders (RDC/TMD) questionnaire. The inclusion and exclusion
      criteria were those included in the RDC/TMD criteria. The bruxism diagnosis was
      drawn from the question, 'Have you been told, or do you notice that you grind
      your teeth or clench your jaw while sleeping at night?' in the anamnestic portion
      of the questionnaire. A bivariate analysis was conducted, comparing the presence
      of perceived parafunctional activity with age (over age 60 and under age 60),
      gender, different subtypes of TMD, pain intensity, grade of chronic pain and
      presence of self-perceived locked joints. The overall prevalence of self-reported
      sleep bruxism (SB) was 54.51%. A statistically significant association was found
      between the presence of SB and patients under age 60, women, greater pain
      intensity, greater pain interference with activities of daily living, and the
      axis-I groups affected by both muscular and articular pathology. There is a
      statistically significant association between self-reported sleep bruxism and
      women under age 60 who have painful symptoms of TMD. There is also a positive
      association between this parafunctional habit and the presence of chronic pain.
      However, more studies that cover larger samples and differentiate between sleep
      bruxism and awake bruxism are needed.

PMID- 24750431
TI  - Cerebrospinal fluid neurofilament light chain levels: marker of progression to
      generalized amyotrophic lateral sclerosis.
AB  - BACKGROUND AND PURPOSE: To evaluate whether cerebrospinal fluid (CSF)
      neurofilament light chain (NFL) levels could predict the time to generalization
      (TTG) in amyotrophic lateral sclerosis (ALS). METHODS: Cerebrospinal fluid NFL
      levels of 37 cases of sporadic ALS were measured and the time of symptom
      spreading from spinal or bulbar localization to both (TTG) was evaluated in all
      patients. RESULTS: Kaplan-Meier analysis showed a short TTG in patients with high
      NFL levels (log-rank test chi-squared = 19.4, P < 0.0001). In a multivariate
      regression model patients with NFL levels above the median had an eight-fold
      higher risk of generalization (adjusted hazard ratio 7.9, 95% confidence interval
      2.9-21.4, P < 0.0001) compared with those with NFL levels below the median.
      CONCLUSIONS: This study shows that in sporadic ALS NFL, a marker of
      neurodegeneration, is correlated with TTG, a clinical intermediate parameter of
      survivorship.

PMID- 24750432
TI  - Eccrine angiomatous hamartoma: multiple, symmetrical swellings on forearms of a
      10-year-old girl.

PMID- 24750433
TI  - Cannabinoid 1 receptors in keratinocytes attenuate fluorescein isothiocyanate
      induced mouse atopic-like dermatitis.
AB  - Atopic dermatitis is a chronic inflammatory disease characterized by an impaired
      epidermal barrier function combined with a chronic Th2-type inflammatory response
      and an intense pruritus. Here, we used an experimental mouse model for Th2-type
      contact hypersensitivity (CHS) to fluorescein isothiocyanate (FITC) to
      investigate the potential role of cannabinoid 1 receptors (CB1) in the
      pathophysiology of mouse atopic-like dermatitis. Mice lacking CB1 receptors
      globally (Cnr1(-/-) ) or specifically in keratinocytes (KC-Cnr1(-/-) ) as well as
      wild-type (WT) control mice were sensitized and challenged with FITC. We examined
      ear swelling responses, transepidermal water loss, Th2-type skin inflammatory
      responses and serum IgE levels. Both Cnr1(-/-) and KC-Cnr1(-/-) showed enhanced
      CHS responses to FITC and a delayed epidermal barrier repair when compared with
      WT mice. mRNA levels for IL-4, thymic stromal lymphopoietin (TSLP) and CCL8, as
      well as eosinophil activity, were significantly increased in inflamed ear tissue
      of FITC-challenged Cnr1(-/-) and KC-Cnr1(-/-) mice. Importantly, CB1 receptor
      deficient keratinocytes secreted increased levels of TSLP, a proinflammatory
      mediator that drives Th2-type skin inflammation in atopic dermatitis, under basal
      and Th2-type inflammatory conditions. Taken together, our results demonstrate
      that CB1 receptors in keratinocytes help to maintain epidermal barrier
      homoeostasis and attenuate Th2-type allergic inflammatory responses. Based on our
      work, we propose that enhanced epidermal allergen penetrance cooperates with
      increased production of TSLP and CCL8 by epidermal keratinocytes for the
      induction of type 2 CD4+ T helper cells. Our results place keratinocytes at the
      cross-roads of outside-in and inside-out pathophysiologic mechanisms of atopic
      dermatitis.

PMID- 24750434
TI  - Measuring progress towards achieving Millennium Development Goals in small
      populations: is under-five mortality in Tuvalu declining?
AB  - OBJECTIVES: Infant mortality rates (IMR) and under-five mortality rates (U5MR) in
      Tuvalu (2010 population 11,149) for 1990-2011 were evaluated to determine best
      estimates of levels and trends. METHODS: Estimates were graphed over time to
      identify trends/inconsistencies, and censored for reliability/plausibility. Where
      possible, 95% confidence intervals (CIs) and tests for linear trend were
      calculated. RESULTS: Ministry of Health (MoH) data indicates IMR and U5MR (per
      1,000 live births) declined over 1990-2008: IMR 62 (95%CI 46-81) for 1991-93 (51
      deaths) to 19 (95%CI 10-33) for 2006-08 (12 deaths); U5MR 67 (95%CI 50-87) for
      1991-93 (55 deaths) to 19 (95%CI 10-33) for 2006-08 (12 deaths). The 2007
      Demographic and Health Survey (DHS) suggests recent trends are increasing: IMR 24
      for 1998-2002 to 31 (95%CI 20-42) for 2003-07; U5MR 29 for 1998-2002 to 36 (95%CI
      30-43) for 2003-07 (deaths not provided). Tests for linear trend and 95%CIs
      indicate MoH declines are statistically significant, but recent increased
      estimates from DHS are not, and could be affected by recall bias. CONCLUSIONS:
      Small populations provide challenges in interpretation of IMR/U5MR trends. To
      ensure the correct interpretation of rates, CIs (95%) and tests for trend should
      be calculated. Tuvalu has experienced steady decline in IMR/U5MR over the past 20
      years.

PMID- 24750435
TI  - Survival and complication rates of fixed restorations supported by locking-taper
      implants: a prospective study with 1 to 10 years of follow-up.
AB  - PURPOSE: The aim of this 10-year follow-up study was to evaluate the implant
      survival and complication rates of fixed restorations supported by locking-taper
      implants. MATERIALS AND METHODS: Over a 10-year period (January 2002 to December
      2011) all patients referred to a single private practice for treatment with fixed
      restorations (single crowns, SCs; fixed partial prostheses, FPPs; fixed full
      arches, FFAs) supported by dental implants were considered for inclusion in the
      study. At each annual follow-up session, clinical, radiographic, and prosthetic
      parameters were assessed. The surviving implant-supported restorations were
      defined as "complication free" in the absence of any biological or prosthetic
      (mechanical or technical) complication. The cumulative implant survival and the
      "complication-free" survival of fixed implant-supported restorations were
      identified using the Kaplan-Meier method. The Log-rank test was used to identify
      correlations between the study variables. RESULTS: In total, 1494 locking-taper
      implants (727 maxilla, 767 mandible) were placed in 642 patients (356 males, 286
      females). Nineteen implants (12 maxilla, 7 mandible) failed. Implant failures
      were attributed to lack of osseointegration (14 implants), peri-implantitis (4
      implants), and mechanical overloading (1 implant). An overall 10-year cumulative
      implant survival rate of 98.7% (98.3% maxilla, 99.1% mandible) was found. The
      implant survival rates did not significantly differ with respect to implant
      location, position, bone type, implant length and diameter, and type of
      restorations. Among the surviving implant-supported restorations (478 SC, 242
      FPP, 19 FFA), a few biological (11/739: 1.4%) and prosthetic (27/739: 3.6%)
      complications were reported. The incidence of mechanical complications was low
      (3/739: 0.4%), with three loosened abutments in three SCs (3/478: 0.6%), and no
      abutment fractures; technical complications were more frequent (24/739: 3.2%),
      with an incidence of decementation of 2.0% (SC 2.0%, FPP 1.6%, FFA 5.2%) and
      ceramic/veneer chipping/fracture of 1.2% (SC 0.0%, FPP 2.8%, FFA 10.5%). A 10
      year cumulative "complication-free" survival of restorations of 88.6% (SC 91.7%,
      FPP 83.1%, FFA 73.8%) was reported. The complication rates differ significantly
      with respect to the type of restoration (p < 0.05). CONCLUSIONS: Fixed
      restorations on locking-taper implants seem to be a successful procedure for the
      rehabilitation of partially and completely edentulous arches.

PMID- 24750436
TI  - Hantavirus infections.
AB  - Over the past few decades understanding and recognition of hantavirus infection
      has greatly improved worldwide, but both the amplitude and the magnitude of
      hantavirus outbreaks have been increasing. Several novel hantaviruses with
      unknown pathogenic potential have been identified in a variety of insectivore
      hosts. With the new hosts, new geographical distributions of hantaviruses have
      also been discovered and several new species were found in Africa. Hantavirus
      infection in humans can result in two clinical syndromes: haemorrhagic fever with
      renal syndrome (HFRS) and hantavirus cardiopulmonary syndrome (HCPS) caused by
      Old World and New World hantaviruses, respectively. The clinical presentation of
      HFRS varies from subclinical, mild, and moderate to severe, depending in part on
      the causative agent of the disease. In general, HFRS caused by Hantaan virus,
      Amur virus and Dobrava virus are more severe with mortality rates from 5 to 15%,
      whereas Seoul virus causes moderate and Puumala virus and Saaremaa virus cause
      mild forms of disease with mortality rates <1%. The central phenomena behind the
      pathogenesis of both HFRS and HCPS are increased vascular permeability and acute
      thrombocytopenia. The pathogenesis is likely to be a complex multifactorial
      process that includes contributions from immune responses, platelet dysfunction
      and the deregulation of endothelial cell barrier functions. Also a genetic
      predisposition, related to HLA type, seems to be important for the severity of
      the disease. As there is no effective treatment or vaccine approved for use in
      the USA and Europe, public awareness and precautionary measures are the only ways
      to minimize the risk of hantavirus disease.

PMID- 24750438
TI  - Impact of postoperative renal replacement therapy on long-term outcome after
      cardiac surgery increases with age.
AB  - BACKGROUND AND AIM OF THE STUDY: In the present study, we investigated the
      survival of patients who received postoperative renal replacement therapy (RRT)
      after cardiac surgery. We specifically focused on factors predicting long-term
      outcome in elderly patients. METHODS: Data of all patients that received
      unintentional renal replacement therapy following cardiac surgery between 2004
      and 2010 were analyzed. Logistic- and Cox regression analyses were performed to
      detect the predictors of early and late mortality, respectively. RESULTS: During
      the study period, 11,899 patients underwent cardiac surgery in our center. Post
      operative RRT was performed in 138 patients (1.2%). In this group of patients, 30
      day mortality included 72 patients (52%) and the total overall mortality included
      107 patients (77.5%). Regression analyses revealed that age predicted 30-day
      mortality (odds ratio = 1.08 [1.03 to 1.12]) as well as late mortality (odds
      ratio = 1.05 [1.02 to 1.07]. CONCLUSIONS: Patients requiring RRT after cardiac
      surgery have a poor prognosis with a high mortality. Older age predicted both 30
      day and late mortality in these patients.

PMID- 24750437
TI  - Interacting effects of warming and drought on regeneration and early growth of
      Acer pseudoplatanus and A. platanoides.
AB  - Climate change is acting on several aspects of plant life cycles, including the
      sexual reproductive stage, which is considered amongst the most sensitive life
      cycle phases. In temperate forests, it is expected that climate change will lead
      to a compositional change in community structure due to changes in the dominance
      of currently more abundant forest tree species. Increasing our understanding of
      the effects of climate change on currently secondary tree species recruitment is
      therefore important to better understand and forecast population and community
      dynamics in forests. Here, we analyse the interactive effects of rising
      temperatures and soil moisture reduction on germination, seedling survival and
      early growth of two important secondary European tree species, Acer
      pseudoplatanus and A. platanoides. Additionally, we analyse the effect of the
      temperature experienced by the mother tree during seed production by collecting
      seeds of both species along a 2200-km long latitudinal gradient. For most of the
      responses, A. platanoides showed higher sensitivity to the treatments applied,
      and especially to its joint manipulation, which for some variables resulted in
      additive effects while for others only partial compensation. In both species,
      germination and survival decreased with rising temperatures and/or soil moisture
      reduction while early growth decreased with declining soil moisture content. We
      conclude that although A. platanoides germination and survival were more affected
      after the applied treatments, its initial higher germination and larger seedlings
      might allow this species to be relatively more successful than A. pseudoplatanus
      in the face of climate change. 

PMID- 24750439
TI  - Proposal for new European pharmaceutical legislation to permit access to custom
      made anti-sense oligonucleotide medicinal products.
AB  - Current European pharmaceutical legislation is not adequate to meet advances in
      science and technologies that will lead to rapid development of custom-made
      medicines. Using existing legislation for custom-made medical devices as a
      template and anti-sense oligonucleotides as model medicinal products, we propose
      new European pharmaceutical legislation to permit timely access to custom-made
      anti-sense oligonucleotide medicinal products. The proposals may be more widely
      applicable to other medicinal products.

PMID- 24750440
TI  - Associations between the pre-pregnancy body mass index and gestational weight
      gain with pregnancy outcomes in Japanese women.
AB  - AIM: To examine the associations between the pre-pregnancy body mass index (BMI)
      and gestational weight gain (GWG) with pregnancy outcomes in Japanese women.
      METHODS: The medical records of 1883 Japanese women who delivered singleton
      infants from January 2010 to January 2013 at Osaka-Minami Medical Center were
      retrospectively reviewed. We use the BMI classification which the World Health
      Organization defined for Asian populations and the GWG classified based on the
      current 2009 Institute of Medicine (IOM) recommendations. The odds ratio (OR) of
      each of the groups for the different pregnancy outcomes were compared to the
      recommended group using a logistic regression analysis adjusted by age,
      gestational weeks, parity, weight gain, mode of delivery, pregnancy induced
      hypertension (PIH) and gestational diabetes mellitus. RESULTS: Women who were
      obese (BMI, >=25 kg/m(2) ) and overweight (BMI, 23-24.9 kg/m(2) ) had a higher
      rate of developing PIH (adjusted OR, 6.68 and 3.21 [95% confidence interval [CI],
      3.31-13.3 and 1.29-7.24]). In contrast, GWG exhibited a correlation with the
      weight of the infant. The inadequate GWG group had a higher rate of small-for
      gestational age (SGA) infants (adjusted OR, 1.72 [95% CI, 1.22-2.46]). The rate
      of emergency cesarean section was not significantly different between the groups.
      CONCLUSION: A pre-pregnancy BMI less than 23 kg/m(2) is desirable to prevent
      Japanese women from developing PIH. GWG within the IOM recommendations also
      reduced the risk of PIH and SGA.

PMID- 24750441
TI  - Selective regulation of the chitin-induced defense response by the Arabidopsis
      receptor-like cytoplasmic kinase PBL27.
AB  - Recognition of microbe-associated molecular patterns (MAMPs) initiates pattern
      triggered immunity in host plants. Pattern recognition receptors (PRRs) and
      receptor-like cytoplasmic kinases (RLCKs) are the major components required for
      sensing and transduction of these molecular patterns. However, the regulation of
      RLCKs by PRRs and their specificity remain obscure. In this study we show that
      PBL27, an Arabidopsis ortholog of OsRLCK185, is an immediate downstream component
      of the chitin receptor CERK1 and contributes to the regulation of chitin-induced
      immunity in Arabidopsis. Knockout of PBL27 resulted in the suppression of several
      chitin-induced defense responses, including the activation of MPK3/6 and callose
      deposition as well as in disease resistance against fungal and bacterial
      infections. On the other hand, the contribution of PBL27 to flg22 signaling
      appears to be very limited, suggesting that PBL27 selectively regulates defense
      signaling downstream of specific PRR complexes. In vitro phosphorylation
      experiments showed that CERK1 preferentially phosphorylated PBL27 in comparison
      to BIK1, whereas phosphorylation of PBL27 by BAK1 was very low compared with that
      of BIK1. Thus, the substrate specificity of the signaling receptor-like kinases,
      CERK1 and BAK1, may determine the preference of downstream RLCKs. 

PMID- 24750442
TI  - Mouse bone marrow-derived dendritic cells can phagocytize the Sporothrix
      schenckii, and mature and activate the immune response by secreting interleukin
      12 and presenting antigens to T lymphocytes.
AB  - In sporotrichosis, dermal dendritic cells were considered to participate in
      induction of the immune responses against Sporothrix schenckii infection.
      However, it is still unclear whether and how dermal dendritic cells were involved
      in the progress. To clarify the pathogenic role of dermal dendritic cells (DC) in
      sporotrichosis, we examined the phagocytosis, maturation stages, cytokine
      production and antigen-presenting ability of mouse bone marrow-derived DC after
      stimulation with S. schenckii. By analysis of flow cytometry, electron microscope
      and confocal microscope, mouse bone marrow-derived DC were proved to be able to
      phagocytize the S. schenckii. The increased expression of CD40, CD80 and CD86 on
      the surface of S. schenckii-pulsed mouse bone marrow-derived DC was detected by
      flow cytometer, indicating that the S. schenckii-pulsed mouse bone marrow-derived
      DC underwent the maturation program. The secretory enhancement of interleukin
      (IL)-12, but not IL-4, was found in S. schenckii-pulsed mouse bone marrow-derived
      DC, suggesting the possible activation of T-helper 1 prone immune responses.
      Furthermore, S. schenckii-pulsed mouse bone marrow-derived DC were demonstrated
      to be capable of inducing the proliferation of T lymphocytes from BALB/c mice
      that were pre-sensitized with S. schenckii. Together, all the results implied
      that dermal DC may participate in the induction of immune responses against S.
      schenckii infection in sporotrichosis. 

PMID- 24750443
TI  - The effect of striatal pre-enkephalin overexpression in the basal ganglia of the
      1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine mouse model of Parkinson's disease.
AB  - The midbrain dopamine (DA) cell death underlying Parkinson's disease (PD) is
      associated with upregulation of pre-enkephalin (pENK) in striatopallidal neurons.
      Our previous results obtained with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine
      (MPTP) parkinsonian monkeys suggest that increased striatal expression of pENK
      mRNA is a compensatory mechanism to alleviate PD-related motor symptoms. In this
      study, we tested the hypothesis that increased pENK expression in the striatum
      protects against the neurotoxic insults of MPTP in mice. To this end, recombinant
      adeno-associated virus serotype 2 also containing green fluorescent protein was
      used to overexpress pENK prior to DA depletion. Our results showed that
      overexpression of pENK in the striatum of MPTP mice induced: (i) increased levels
      of the opioid peptide enkephalin (ENK) in the striatum; (ii) higher densities of
      ENK-positive fibers in both the globus pallidus (GP) and the substantia nigra;
      (iii) higher locomotor activity; and (iv) a higher density of striatal tyrosine
      hydroxylase-positive fibers in the striatum. In addition, striatal overexpression
      of pENK in MPTP -treated mice led to 52 and 43% higher DA concentrations and DA
      turnover, respectively, in the GP compared to sham-treated MPTP mice. These
      observations are in agreement with the idea that increased expression of pENK at
      an early stage of disease can improve PD symptoms. 

PMID- 24750444
TI  - Involvement of satellite I noncoding RNA in regulation of chromosome segregation.
AB  - Human centromeres consist of repetitive sequences from which satellite I
      noncoding RNAs are transcribed. We found that knockdown of satellite I RNA causes
      abnormal chromosome segregation and generation of nuclei with a grape-shape
      phenotype. Co-immunoprecipitation experiments showed that satellite I RNA
      associates with Aurora B, a component of the chromosome passenger complex (CPC)
      regulating proper attachment of microtubules to kinetochores, in mitotic HeLa
      cells. Satellite I RNA was also shown to associate with INCENP, another component
      of the CPC. In addition, depletion of satellite I RNA resulted in up-regulation
      of kinase activity of Aurora B and delocalization of the CPC from the centromere
      region. These results suggest that satellite I RNA is involved in chromosome
      segregation through controlling activity and centromeric localization of Aurora B
      kinase. 

PMID- 24750445
TI  - Reproductive factors and Parkinson's disease risk in Danish women.
AB  - BACKGROUND AND PURPOSE: Parkinson's disease is more common in men than women by a
      ratio of about 1.5:1 and yet there is no consensus to date as to whether female
      reproductive factors including hormone use affect Parkinson's disease risk. Our
      objective was to examine the relationship between Parkinson's disease and female
      reproductive factors in the largest population-based Parkinson's disease case
      control study to date. METHODS: Seven hundred and forty-three female Parkinson's
      disease cases diagnosed between 1996 and 2009 were selected from the Danish
      National Hospital Register, diagnoses confirmed by medical record review, and the
      cases were matched by birth year to 765 female controls randomly selected from
      the Danish Civil Registration System. Covariate information was collected in
      computer-assisted telephone interviews covering an extensive array of topics
      including reproductive and lifestyle factors. RESULTS: After adjusting for
      smoking, caffeine and alcohol use, education, age, and family Parkinson's disease
      history, inverse associations between Parkinson's disease and early menarche
      (first period at <=11 years), oral contraceptives, high parity (>=4 children) and
      bilateral oophorectomy were found; adjusted odds ratios and 95% confidence limits
      were respectively 0.68 (0.45-1.03) for early menarche, 0.87 (0.69-1.10) for oral
      contraceptives, 0.79 (0.59-1.06) for high parity and 0.65 (0.45-0.94) for
      bilateral oophorectomy. Little support for associations between Parkinson's
      disease and fertile life length, age at menopause or post-menopausal hormone
      treatment was found. CONCLUSIONS: Reproductive factors related to women's early-
      to mid-reproductive lives appear to be predictive of subsequent Parkinson's
      disease risk whereas factors occurring later in life seem less important.

PMID- 24750446
TI  - Transcobalamin II (TCN2 67A>G and TCN2 776C>G) and transcobalamin II receptor
      (TCblR 1104C>T) polymorphisms in Korean patients with idiopathic recurrent
      spontaneous abortion.
AB  - PROBLEM: The transcobalamin II (TCN2) 776C>G polymorphism has been reported to be
      a genetic risk factor for idiopathic recurrent spontaneous abortion (RSA).
      However, the sample size in previous studies was small, and other TCN2
      polymorphisms have not been studied. Moreover, the TCN2 67A>G and 776C>G
      polymorphisms, and the transcobalamin II receptor (TCblR/CD320) 1104C>T
      polymorphism, have demonstrated associations with immune responses. METHOD OF
      STUDY: Three hundred and seventy-eight RSA patients who had at least two
      consecutive spontaneous abortions were enrolled. Two hundred and seven control
      subjects were collected from a convenience sample. Polymerase chain reaction and
      restriction fragment length polymorphism analysis were performed to identify the
      TCN2 67A>G and 776C>G polymorphisms, and the TCblR 1104C>T polymorphism. RESULTS:
      RSA patients showed significantly different frequencies of the TCN2 67AG+GG
      genotypes compared with control subjects. CONCLUSION: The TCN2 67G allele is a
      possible risk factor for idiopathic RSA.

PMID- 24750448
TI  - Autoimmune progesterone dermatitis that changed its clinical manifestation from
      anaphylaxis to fixed drug eruption-like erythema.

PMID- 24750447
TI  - Saliva as a potential tool for diagnosis of dry mouth including Sjogren's
      syndrome.
AB  - OBJECTIVES: Recently, the use of saliva as a diagnostic tool has gained
      considerable attention because it is non-invasive and easy to perform repeatedly.
      In this study, we focused on soluble molecules in saliva to establish a new
      diagnostic method for xerostomia. MATERIALS AND METHODS: Saliva was obtained from
      90 patients with Sjogren's syndrome (SS), 22 patients with xerostomia associated
      with neurogenic/neuropsychiatric disorders and drugs (XND), 30 patients with
      radiation-induced xerostomia (RX), and 36 healthy controls. Concentrations of
      helper T (Th) cytokines in saliva were measured by flow cytometric analysis.
      Concentrations of secretory IgA (SIgA) and chromogranin A (CgA) were measured by
      ELISA. RESULTS: Unstimulated and stimulated whole saliva from patients with SS,
      XND, and RX was significantly reduced compared with controls. Th1 and Th2
      cytokines from SS patients were significantly higher than controls. Furthermore,
      Th2 cytokines were closely associated with strong lymphocytic accumulation in
      salivary glands from SS patients, while Th1 and Th17 cytokines were negatively
      associated. SIgA levels were not significantly different between all patient
      groups and controls. CgA levels from XND patients were significantly higher than
      controls. CONCLUSIONS: The measurement of cytokines, CgA, and SIgA in saliva is
      suggested to be useful for the diagnosis of xerostomia and also to reveal disease
      status.

PMID- 24750449
TI  - Influence of surgical and prosthetic techniques on marginal bone loss around
      titanium implants. Part I: immediate loading in fresh extraction sockets.
AB  - PURPOSE: Delayed placement of implant abutments has been associated with peri
      implant marginal bone loss; however, long-term results obtained by modifying
      surgical and prosthetic techniques after implant placement are still lacking.
      This study aimed to evaluate the marginal bone loss around titanium implants
      placed in fresh extraction sockets using two loading protocols after a 5-year
      follow-up period. MATERIAL AND METHODS: A total of 36 patients received 40
      titanium implants (Astra Tech) intended for single-tooth replacement. Implants
      were immediately placed into fresh extraction sockets using either a one-stage
      (immediate loading by placing an interim prosthesis into functional occlusion) or
      a two-stage prosthetic loading protocol (insertion of abutments after 8 weeks of
      healing time). Marginal bone levels relative to the implant reference point were
      evaluated at four time intervals using intraoral radiographs: at time of implant
      placement, and 1, 3, and 5 years after implant placement. Measurements were
      obtained from mesial and distal surfaces of each implant (alpha = 0.05). RESULTS:
      One-stage immediate implant placement into fresh extraction sockets resulted in a
      significant reduction in marginal bone loss (p < 0.002) compared to the
      traditional two-stage technique. Whereas mesial surfaces remained stable for the
      5-year observation period, significant marginal bone loss was observed on distal
      surfaces of implants after cementation of interim prostheses (p < 0.007) and
      after 12 months (p < 0.034). CONCLUSIONS: Within the limitations of this study,
      immediate loading of implants placed into fresh extraction sockets reduced
      marginal bone loss and did not compromise the success rate of the restorations.

PMID- 24750450
TI  - Laser light passage through restored and carious posterior teeth.
AB  - Laser Doppler flowmetry (LDF) has been used to investigate pulpal blood flow as a
      means of pulp vitality testing. Transmission of laser light from the tooth
      surface to the pulp space may be influenced by caries and restorations. One
      hundred and twenty-two first and second molars that had caries into dentine,
      restorations or significant loss of coronal tissue were sectioned in half axio
      bucco-lingually. The two sections were illuminated with a laser from their buccal
      and lingual aspects 2 mm coronal to the amelocemental junction. Light reaching
      the pulp space was recorded. Buccal and lingual illumination sites were equally
      effective for 67 teeth (55%). Buccal sites alone were effective for 35 teeth
      (29%), despite over one-third of these surfaces being restored or featuring
      enamel or dentine caries. A lingual position alone was effective for 20 teeth
      (16%). Caries affected light transmission, but for over half the teeth, the pulp
      could be illuminated from all four probe positions. No effect was found when the
      influence of mesial and distal restorations on transmission into the
      corresponding tooth section was examined. The pulp spaces of most (84%) restored,
      and carious posterior teeth could be illuminated by laser light from their buccal
      aspect and these teeth could potentially be vitality tested using LDF.

PMID- 24750451
TI  - Effect of artificial insemination protocol and dose of frozen/thawed stallion
      semen on pregnancy results in mares.
AB  - Deep intra-uterine insemination is commonly accepted as a routine procedure for
      artificial insemination in horses. The motives and principles of deep
      insemination are well described, but the equipment used may differ. In this
      trial, the efficiency of two different insemination pipettes for deep intra
      uterine insemination in the mare was compared with insemination into the uterine
      body using commercially available frozen-thawed semen of two stallions of proven
      fertility. These inseminations were performed using two different doses. The semi
      flexible Minitube pipette was compared with a newly designed insemination device
      with a more flexible telescopic insemination catheter (Ghent device). The semi
      flexible Minitube pipette performed better than the newly designed insemination
      device with respect to pregnancy outcome (p = 0.008). The superiority of deep
      horn insemination over uterine body insemination was reflected by the better
      pregnancy rates obtained after deep insemination using the same low doses (30.6%
      better pregnancy rates) (p = 0.0123). 

PMID- 24750452
TI  - Genotype differences in the metabolism of proline and polyamines under moderate
      drought in tomato plants.
AB  - Water stress is one of the most important factors limiting the growth and
      productivity of crops. The implication of compatible osmolytes such as proline
      and polyamines in osmotic adjustment has been widely described in numerous plants
      species under stress conditions. In the present study, we investigated the
      response of five cherry tomato cultivars (Solanum lycopersicum L.) subjected to
      moderate water stress in order to shed light on the involvement of proline and
      polyamine metabolism in the mechanisms of tolerance to moderate water stress. Our
      results indicate that the most water stress-resistant cultivar (Zarina) had
      increased degradation of proline associated with increased polyamine synthesis,
      with a higher concentration of spermidine and spermine under stress conditions.
      In contrast, Josefina, the cultivar most sensitive to water stress, showed a
      proline accumulation associated with increased synthesis after being subjected to
      stress. In turn, in this cultivar, no rise in polyamine synthesis was detected.
      Therefore, all the data appear to indicate that polyamine metabolism is more
      involved in the tolerance response to moderate water stress. 

PMID- 24750453
TI  - Non-equilibrium atmospheric pressure plasmas modulate cell cycle-related gene
      expressions in melanocytic tumors of RET-transgenic mice.
AB  - The incidence of cutaneous malignant melanoma is increasing at a greater rate
      than that of any other cancer in the world. However, an effective therapy for
      malignant melanoma has not been established. Recently, some studies have shown an
      antitumor effect of non-equilibrium atmospheric pressure plasmas (NEAPPs) in
      vitro. Here, we examined the in vivo effect of NEAPP on cell cycle regulators,
      key elements for malignant transformation, in spontaneously developed benign
      melanocytic tumors in a hairless animal model. NEAPP irradiation decreased
      expression levels of cell cycle promoters, Cyclin D1, E1 and E2, and increased
      expression level of a cell cycle repressor, p27(KIP) (1) . Cyclin D1, E1 and E2
      and p27(KIP) expression levels were associated with malignant transformation of
      the benign tumor in the animal model. Our results suggest that NEAPP irradiation
      suppresses malignant transformation of a benign melanocytic tumor via control of
      the expression levels of cell cycle regulators.

PMID- 24750454
TI  - A cost-effectiveness analysis of online, radio and print tobacco control
      advertisements targeting 25-39 year-old males.
AB  - OBJECTIVE: To assess the relative cost-effectiveness of various non-television
      advertising media in encouraging 25-39 year-old male smokers to respond to a
      cessation-related call to action. Information about how new electronic media
      compare in effectiveness is important to inform the implementation of future
      tobacco control media campaigns. METHODS: Two testimonial advertisements
      featuring members of the target group were developed for radio, press and online
      media. Multiple waves of media activity were scheduled over a period of seven
      weeks, including an initial integrated period that included all three media and
      subsequent single media phases that were interspersed with a week of no media
      activity. The resulting Quit website hits, Quitline telephone calls, and
      registrations to online and telephone counselling services were compared to
      advertising costs to determine the relative cost-effectiveness of each media in
      isolation and the integrated approach. RESULTS: The online-only campaign phase
      was substantially more cost-effective than the other phases, including the
      integrated approach. CONCLUSIONS: This finding is contrary to the current
      assumption that the use of a consistent message across multiple media
      simultaneously is the most cost-effective way of reaching and affecting target
      audiences. IMPLICATIONS: Online advertising may be a highly cost-effective
      channel for low-budget tobacco control media campaigns.

PMID- 24750455
TI  - Rasburicase-induced methemoglobinemia in two African-American female patients: an
      under-recognized and continued problem.
AB  - Rasburicase-induced methemoglobinemia is a known adverse effect of patients
      administered rasburicase for tumor lysis syndrome who have concomitant glucose-6
      phosphate dehydrogenase deficiency. This phenomenon has been described in
      multiple case reports but has been limited to male patients. We present the first
      case series illustrating this adverse effect in two female patients where
      morbidity and mortality associated with rasburicase-induced methemoglobinemia
      were evident. Screening protocols at the reporting institutions were lacking. The
      prevalence of G6PD may be underestimated based on the epidemiology of sample
      subjects in previous studies of rasburicase. We argue that both male and female
      patients should be suspected of G6PD in this setting; however, more data on
      prevalence and cost-effectiveness are needed on screening protocols for G6PD. 

PMID- 24750456
TI  - Complex phylogeography and historical hybridization between sister taxa of
      freshwater sculpin (Cottus).
AB  - Species ranges that span different geographic landscapes frequently contain
      cryptic species- or population-level structure. Identifying these possible
      diversification factors can often be accomplished under a comparative
      phylogeographic framework. However, comparisons suffer if previous studies are
      limited to a particular group or habitat type. In California, a complex landscape
      has led to several phylogeographic breaks, primarily in terrestrial species.
      However, two sister taxa of freshwater fish, riffle sculpin (Cottus gulosus) and
      Pit sculpin (Cottus pitensis), display ranges based on morphological
      identifications that do not coincide with these breaks. Using a comprehensive
      sampling and nuclear, mitochondrial and microsatellite markers, we hypothesized
      that proposed species ranges are erroneous based on potential hybridization/gene
      flow between species. Results identified a phylogeographic signature consistent
      with this hypothesis, with breaks at the Coast Range Mountains and Sacramento/San
      Joaquin River confluence. Coastal locations of C. gulosus represent a unique
      lineage, and 'true' C. gulosus were limited to the San Joaquin basin, both
      regions under strong anthropogenic influence and potential conservation targets.
      C. pitensis limits extended historically throughout the Sacramento/Pit River
      basin but currently are restricted to the Pit River. Interestingly, locations in
      the Sacramento River contained low levels of ancestral hybridization and gene
      flow from C. gulosus but now appear to be a distinct population. The remaining
      population structure was strongly correlated with Sierra Nevada presence (high)
      or absence (low). This study stresses the importance of testing phylogeographic
      breaks across multiple taxa/habitats before conservation decisions are made, but
      also the potential impact of different geographic landscapes on evolutionary
      diversification. 

PMID- 24750457
TI  - Enhanced recovery after pancreatic surgery: a systematic review of the evidence.
AB  - BACKGROUND: Enhanced recovery after surgery (ERAS) protocols have been shown to
      reduce hospital stay without compromising outcomes. Attempts to apply ERAS
      principles in the context of pancreatic surgery have generated encouraging
      results. A systematic review of the current evidence for ERAS following
      pancreatic surgery was conducted. METHODS: A literature search of MEDLINE,
      CINAHL, EMBASE and the Cochrane Library was performed for articles describing
      postoperative clinical pathways in pancreatic surgery during the years 2000-2013.
      The keywords 'clinical pathway', 'critical pathway', 'fast-track', 'pancreas' and
      'surgery' and their synonyms were used as search terms. Articles were selected
      for inclusion based on predefined criteria and ranked for quality. Details of the
      ERAS protocols and relevant outcomes were extracted and analysed. RESULTS: Ten
      articles describing an ERAS protocol in pancreatic surgery were identified. The
      level of evidence was graded as low to moderate. No articles reported an adverse
      effect of an ERAS protocol for pancreatic surgery on perioperative morbidity or
      mortality. Length of stay (LoS) was decreased and readmission rates were found to
      be unchanged in six of seven studies that compared these outcomes. CONCLUSIONS:
      Evidence indicates that ERAS protocols may be implemented in pancreatic surgery
      without compromising patient safety or increasing LoS. Enhanced recovery after
      surgery programmes in the context of pancreatic surgery should be standardized
      based upon the best available evidence, and trials of ERAS programmes involving
      multiple centres should be performed.

PMID- 24750458
TI  - Minilaparoscopic hysterectomy made easy: first report on alternative
      instrumentation and new integrated energy platform.
AB  - Minilaparoscopy is an attractive approach for hysterectomy due to advantages such
      as reduced morbidities and enhanced cosmesis. However, it has not been
      popularized due to the lack of suitable instruments and high technical demand. We
      aim to highlight the first case of minilaparoscopic hysterectomy reported in Asia
      and the use of a new integrated energy platform, Thunderbeat. We would like to
      propose an alternative method of instrumentation, so as to improve the
      feasibility and safety of minilaparoscopic hysterectomy. The first
      minilaparoscopic hysterectomy in Singapore was successfully completed using the
      alternative instrumentation and new energy platform. There was no conversion or
      complication during the surgery. The patient recovered uneventfully. To our
      knowledge, this is the first report on the use of such alternative
      instrumentation. This approach in instrumentation and the new energy platform
      will improve the feasibility and speed of the surgery and ensure safety in our
      patients. 

PMID- 24750459
TI  - Oral health status and behaviours of children with Autism Spectrum Disorder: a
      case-control study.
AB  - BACKGROUND: Autism Spectrum Disorder (ASD) is a lifelong neuro-developmental
      disorder characterized by abnormalities in social interactions and communication
      and by stereotyped, repetitive activities. PURPOSE: Assess the oral health status
      and behaviours of children with ASD. METHODS: The study included 100 children
      with ASD and 100 healthy children from Alexandria, Egypt. Data were collected
      using a questionnaire and clinical examination. Questionnaire assessed socio
      demographics, medical history, dental history, oral hygiene, dietary habits, and
      presence of self-injurious behaviours. Clinical examination assessed behaviour
      during examination, gingival condition, plaque accumulation, caries, and other
      oral conditions. RESULTS: Children with ASD had significantly poorer oral hygiene
      and gingival condition than healthy children (P < 0.001 for both). No significant
      differences were found in caries prevalence or experience in primary or permanent
      dentition. More children with ASD behaved 'negatively' or 'definitely negatively'
      (37% and 11%) than did healthy controls (11% and 2%) (P < 0.0001). Self-injurious
      behaviour and bruxism were more practised by children with ASD (32% of children
      with ASD and 2% of healthy children, P < 0.001). More children with ASD had
      difficulty in accessing dental care (P = 0.002). CONCLUSIONS: The oral condition
      of children with ASD might increase the risk of developing dental diseases. Their
      behaviour and life factors may complicate provision of services and limit access
      to dental care. Therefore, individualized oral health education programmes should
      be implemented for those children.

PMID- 24750460
TI  - Incidence, risk, and consequences of atrial arrhythmias in patients with
      continuous-flow left ventricular assist devices.
AB  - BACKGROUND: Although atrial arrhythmias (AAs) are common in heart failure, the
      incidence of AAs subsequent to the placement of left ventricular assist devices
      (LVADs) has not been elucidated. METHODS: Patients receiving a HeartMate II LVAD
      in the bridge to transplant (n = 490) and destination therapy (n = 634) trials
      were included (n = 1125). AAs requiring treatment were recorded, regardless of
      symptoms. Using Cox models with and without a 60-day blanking period, risk
      factors for early and late AAs were determined. RESULTS: In total, there were 271
      AAs in 231 patients (21%), most of which occurred within the first 60 days.
      Patients with and without AAs had similar survival (p = 0.16). Serum creatinine
      (hazard ratio [HR] = 1.49 per unit increase, 1.18 to 1.88; p < 0.001) and
      ejection fraction (HR = 0.98 per 1% increase, 0.95 to 0.999; p = 0.04) were
      associated with AAs in a multivariable model. Although quality of life (QoL) and
      functional status improved in all patients, those with AAs had worse unadjusted
      QoL (p < 0.001) and a decreased rate of improvement in six-minute walk distance
      over six to 24 months postimplant (p = 0.016). CONCLUSIONS: Approximately one
      fifth of LVAD patients have AAs, most commonly within the first 60 days of
      support. Preoperative creatinine is a strong risk factor for early and late AAs.
      Although AAs do not impact survival, they are associated with decreased
      functional status and QoL improvements during LVAD support.

PMID- 24750461
TI  - Is it time for a nontechnical skills approach to prescribing?

PMID- 24750462
TI  - A 12-year survey of methicillin-resistant Staphylococcus aureus infections in
      Greece: ST80-IV epidemic?
AB  - Methicillin-resistant Staphylococcus aureus (MRSA) is an important cause of both
      healthcare-associated MRSA (HA-MRSA) and community-associated MRSA (CA-MRSA)
      infections. Severe MRSA infections have been associated with the virulence factor
      Panton-Valentine leukocidin (PVL). The aim of this study was to investigate
      susceptibility patterns, the presence of toxin genes, including that encoding
      PVL, and clonality among MRSA isolates collected from patients in Greece over a
      12-year period. MRSA isolates were collected from January 2001 to December 2012
      from six different hospitals. Antibiotic susceptibility was determined with the
      disk diffusion method and the Etest. The presence of the toxic shock syndrome
      toxin-1 gene (tst), the enterotoxin gene cluster (egc) and the PVL gene was
      tested with PCR. The genotypic characteristics of the strains were analysed by
      SCCmec and agr typing, and clonality was determined with pulsed-field gel
      electrophoresis and multilocus sequence typing. An increasing rate of MRSA among
      S. aureus infections was detected up to 2008. The majority of PVL-positive MRSA
      isolates belonged to a single clone, sequence type (ST)80-IV, which was
      disseminated both in the community and in hospitals, especially during the
      warmest months of the year. Carriage of tst was associated with ST30-IV, whereas
      egc was distributed in different clones. CA-MRSA isolates were recovered mainly
      from skin and soft tissue infections, whereas HA-MRSA isolates were associated
      with surgical and wound infections. During the period 2001-2012, ST80-IV
      predominated in the community and infiltrated the hospital settings in Greece,
      successfully replacing other PVL-positive clones. The predominance of ST239-III
      in HA-MRSA infections was constant, whereas new clones have also emerged.
      Polyclonality was statistically significantly higher among CA-MRSA isolates and
      isolates from adult patients. 

PMID- 24750463
TI  - Immune trypanolysis test with blood spotted on filter paper for epidemiological
      surveillance of sleeping sickness.
AB  - OBJECTIVES: The immune trypanolysis test (TL) is an accurate sero-diagnostic tool
      increasingly implemented for sleeping sickness medical surveillance, but it is
      restricted to the reference laboratories. To facilitate storage and transport of
      the test specimen, we developed a protocol for the examination of blood spotted
      on filter paper (TL-fp) that can be stored and shipped at ambient temperature. We
      compared its performance with the classical TL on plasma (TL-pl) that needs to be
      kept frozen until use. METHODS: The study was conducted in active foci of the
      Republic of Guinea. In total, 438 specimens from treated and untreated sleeping
      sickness patients and serological suspects were tested with both methods. RESULT:
      TL-fp gave significantly less positive results than TL-pl, but all the confirmed
      sleeping sickness cases were positive with the TL-fp protocol. CONCLUSION: TL-fp
      appears to offer a good compromise between feasibility and sensitivity to detect
      currently infected subjects who play a role in the transmission of Trypanosoma
      brucei gambiense and is useful for contributing to the elimination of gambiense
      sleeping sickness.

PMID- 24750464
TI  - Reassortant swine influenza viruses isolated in Japan contain genes from pandemic
      A(H1N1) 2009.
AB  - In 2013, three reassortant swine influenza viruses (SIVs)-two H1N2 and one H3N2
      were isolated from symptomatic pigs in Japan; each contained genes from the
      pandemic A(H1N1) 2009 virus and endemic SIVs. Phylogenetic analysis revealed that
      the two H1N2 viruses, A/swine/Gunma/1/2013 and A/swine/Ibaraki/1/2013, were
      reassortants that contain genes from the following three distinct lineages: (i)
      H1 and nucleoprotein (NP) genes derived from a classical swine H1 HA lineage
      uniquely circulating among Japanese SIVs; (ii) neuraminidase (NA) genes from
      human-like H1N2 swine viruses; and (iii) other genes from pandemic A(H1N1) 2009
      viruses. The H3N2 virus, A/swine/Miyazaki/2/2013, comprised genes from two
      sources: (i) hemagglutinin (HA) and NA genes derived from human and human-like
      H3N2 swine viruses and (ii) other genes from pandemic A(H1N1) 2009 viruses.
      Phylogenetic analysis also indicated that each of the reassortants may have
      arisen independently in Japanese pigs. A/swine/Miyazaki/2/2013 were found to have
      strong antigenic reactivities with antisera generated for some seasonal human
      lineage viruses isolated during or before 2003, whereas A/swine/Miyazaki/2/2013
      reactivities with antisera against viruses isolated after 2004 were clearly
      weaker. In addition, antisera against some strains of seasonal human-lineage H1
      viruses did not react with either A/swine/Gunma/1/2013 or A/swine/Ibaraki/1/2013.
      These findings indicate that emergence and spread of these reassortant SIVs is a
      potential public health risk. 

PMID- 24750466
TI  - Prevalence of congenital hypertrophy of the retinal pigment epithelium (CHRPE) in
      Israel.

PMID- 24750465
TI  - Lack of recombinant factor VIII B-domain induces phospholipid vesicle
      aggregation: implications for the immunogenicity of factor VIII.
AB  - Factor VIII (FVIII) is a multidomain blood plasma glycoprotein. Activated FVIII
      acts as a cofactor to the serine protease factor IXa within the membrane-bound
      tenase complex assembled on the activated platelet surface. Defect or deficiency
      in FVIII causes haemophilia A, a severe hereditary bleeding disorder. Intravenous
      administration of plasma-derived FVIII or recombinant FVIII concentrates restores
      normal coagulation in haemophilia A patients and is used as an effective therapy.
      In this work, we studied the biophysical properties of clinically potent
      recombinant FVIII forms: human FVIII full-length (FVIII-FL), human FVIII B-domain
      deleted (FVIII-BDD) and porcine FVIII-BDD bound to negatively charged
      phospholipid vesicles at near-physiological conditions. We used cryo-electron
      microscopy (Cryo-EM) as a direct method to evaluate the homogeneity and micro
      organization of the protein-vesicle suspensions, which are important for FVIII
      therapeutic properties. Applying concurrent Cryo-EM, circular dichroism and
      dynamic light scattering studies to the three recombinant FVIII forms when bound
      to phospholipid vesicles revealed novel properties for their functional, membrane
      bound state. The three FVIII constructs have similar activity, secondary
      structure distribution and bind specifically to negatively charged phospholipid
      membranes. Human and porcine FVIII-BDD induce strong aggregation of the vesicles,
      but the human FVIII-FL form does not. The proposed methodology is effective in
      characterizing and identifying differences in therapeutic recombinant FVIII
      membrane-bound forms near physiological conditions, because protein-containing
      aggregates are considered to be a factor in increasing the immunogenicity of
      protein therapeutics. This will provide better characterization and development
      of safer and more effective FVIII products with implications for haemophilia A
      treatment. 

PMID- 24750467
TI  - Modulating hair follicle size with Wnt10b/DKK1 during hair regeneration.
AB  - Hair follicles have characteristic sizes corresponding to their cycle-specific
      stage. However, how the anagen hair follicle specifies its size remains elusive.
      Here, we showed that in response to prolonged ectopic Wnt10b-mediated beta
      catenin activation, regenerating anagen hair follicles grew larger in size. In
      particular, the hair bulb, dermal papilla and hair shaft became enlarged, while
      the formation of different hair types (Guard, Awl, Auchene and Zigzag) was
      unaffected. Interestingly, we found that the effect of exogenous WNT10b was
      mainly on Zigzag and less on the other kinds of hairs. We observed dramatically
      enhanced proliferation within the matrix, DP and hair shaft of the enlarged
      AdWnt10b-treated hair follicles compared with those of normal hair follicles at
      P98. Furthermore, expression of CD34, a specific hair stem cell marker, was
      increased in its number to the bulge region after AdWnt10b treatment. Ectopic
      expression of CD34 throughout the ORS region was also observed. Many CD34
      positive hair stem cells were actively proliferating in AdWnt10b-induced hair
      follicles. Importantly, subsequent co-treatment with the Wnt inhibitor, DKK1,
      reduced hair follicle enlargement and decreased proliferation and ectopic
      localization of hair stem cells. Moreover, injection of DKK1 during early anagen
      significantly reduced the width of prospective hairs. Together, these findings
      strongly suggest that Wnt10b/DKK1 can modulate hair follicle size during hair
      regeneration.

PMID- 24750468
TI  - Dissecting the mechanism of Solanum lycopersicum and Solanum chilense flower
      colour formation.
AB  - Flowers are the defining feature of angiosperms, and function as indispensable
      organs for sexual reproduction. Flower colour typically plays an important role
      in attracting pollinators, and can show considerable variation, even between
      closely related species. For example, domesticated tomato (S. lycopersicum) has
      orange/yellow flowers, while the wild relative S. chilense (accession LA2405) has
      bright yellow flowers. In this study, the mechanism of flower colour formation in
      these two species was compared by evaluating the accumulation of carotenoids,
      assessing the expression genes related to carotenoid biosynthetic pathways and
      observing chromoplast ultrastructure. In S. chilense petals, genes associated
      with the lutein branch of the carotenoid biosynthetic pathway, phytoene
      desaturase (PDS), zeta-carotene desaturase (ZDS), lycopene beta-cyclase (LCY-B),
      beta-ring hydroxylase (CRTR-B) and epsilon-ring hydroxylase (CRTR-E), were highly
      expressed, and this was correlated with high levels of lutein accumulation. In
      contrast, PDS, ZDS and CYC-B from the neoxanthin biosynthetic branch were highly
      expressed in S. lycopersicum anthers, leading to increased beta-carotene
      accumulation and hence an orange/yellow colour. Changes in the size, amount and
      electron density of plastoglobules in chromoplasts provided further evidence of
      carotenoid accumulation and flower colour formation. Taken together, these
      results reveal the biochemical basis of differences in carotenoid pigment
      accumulation and colour between petals and anthers in tomato. 

PMID- 24750469
TI  - The endocannabinoid system and the neuroendocrine control of hydromineral
      balance.
AB  - Endocannabinoids (ECBs) are ubiquitous lipophilic agents, and this characteristic
      is consistent with the wide range of homeostatic functions attributed to the ECB
      system. There is an increasing number of studies showing that the ECB system
      affects neurotransmission within the hypothalamic neurohypophyseal system. We
      provide an overview of the primary roles of ECBs in the modulation of
      neuroendocrine function and, specifically, in the control of hydromineral
      homeostasis. Accordingly, the general aspects of ECB-mediated signalling, as well
      as the specific contributions of the central component of the ECB system to the
      integration of behavioural and endocrine responses that control body fluid
      homeostasis, are discussed. 

PMID- 24750470
TI  - Local injection of vasopressin reduces the blood loss during cesarean section in
      placenta previa.
AB  - AIM: The aim of this study was to evaluate the effect of local injection of
      vasopressin on blood loss and secondary impact on complications during cesarean
      section in patients with placenta previa. MATERIAL AND METHODS: We
      retrospectively reviewed the medical records of all patients diagnosed with
      placenta previa admitted to our hospital. Two consecutive periods were compared.
      During period B, 59 patients underwent the local injection of a vasopressin
      solution (4 U in 20 mL of saline) into the placental implantation site after
      placental delivery. During period A, 50 patients underwent cesarean section
      without vasopressin injection, and were analyzed as a control group. The
      estimated blood loss was recorded, as were the complications during surgery. In
      addition, the expression of the vasopressin V1alpha receptor in uterine smooth
      muscle was evaluated by immunohistochemistry. RESULTS: The mean estimated blood
      loss was significantly lower in the vasopressin group than in the control group.
      There were no statistically significant differences with surgical complications.
      The vasopressin V1alpha receptor was highly expressed in smooth muscle cells in
      the lower segment of the uterine body, whereas the immunoreactivity for the
      oxytocin receptor was faint in the lower segment. CONCLUSION: The local injection
      of vasopressin into the placental implantation site significantly reduced the
      blood loss without increasing the morbidity.

PMID- 24750471
TI  - Mastication and jaw motion of partially edentulous patients are affected by
      different implant-based prostheses.
AB  - The main goal of prosthetic treatment is to restore masticatory function.
      However, insufficient evidence supports the recommendation of one specific
      prosthetic intervention for partially edentulous patients. Function after the use
      of three different prostheses by the same partially edentulous subject.
      Mastication was assessed in 12 subjects (mean age 62.6 +/- 7.8 years) after they
      had used removable partial dentures (RPDs), implant-supported partial dentures
      (IRPDs) and implant-fixed partial dentures (IFPDs). Masticatory ability (MA) was
      estimated by visual analogue scale questionnaire, while the mandibular chewing
      motion was evaluated by kinesiographic device, representing an objective
      measurement of masticatory function. Data were analysed by repeated-measures
      anova followed by Tukey-Kramer (P < 0.05). MA improved after IRPD and IFPD use (P
      < 0.05). Opening, closing and total cycle time duration were reduced after both
      IRPD and IFPD use (P < 0.05), irrespectively the implant prosthesis type. IFPDs
      and IRPDs restore the masticatory function of partially edentulous patients
      better than RPDs.

PMID- 24750472
TI  - Removable partial dentures: use of rapid prototyping.
AB  - The CAD/CAM technology associated with rapid prototyping (RP) is already widely
      used in the fabrication of all-ceramic fixed prostheses and in the biomedical
      area; however, the use of this technology for the manufacture of metal frames for
      removable dentures is new. This work reports the results of a literature review
      conducted on the use of CAD/CAM and RP in the manufacture of removable partial
      dentures. 

PMID- 24750473
TI  - Unexpected ancestry of Populus seedlings from a hybrid zone implies a large role
      for postzygotic selection in the maintenance of species.
AB  - In the context of potential interspecific gene flow, the integrity of species
      will be maintained by reproductive barriers that reduce genetic exchange,
      including traits associated with prezygotic isolation or poor performance of
      hybrids. Hybrid zones can be used to study the importance of different
      reproductive barriers, particularly when both parental species and hybrids occur
      in close spatial proximity. We investigated the importance of barriers to gene
      flow that act early vs. late in the life cycle of European Populus by quantifying
      the prevalence of homospecific and hybrid matings within a mosaic hybrid zone. We
      obtained genotypic data for 11 976 loci from progeny and their maternal parents
      and constructed a Bayesian model to estimate individual admixture proportions and
      hybrid classes for sampled trees and for the unsampled pollen parent. Matings
      that included one or two hybrid parents were common, resulting in admixture
      proportions of progeny that spanned the whole range of potential ancestries
      between the two parental species. This result contrasts strongly with the
      distribution of admixture proportions in adult trees, where intermediate hybrids
      and each of the parental species are separated into three discrete ancestry
      clusters. The existence of the full range of hybrids in seedlings is consistent
      with weak reproductive isolation early in the life cycle of Populus. Instead, a
      considerable amount of selection must take place between the seedling stage and
      maturity to remove many hybrid seedlings. Our results highlight that high
      hybridization rates and appreciable hybrid fitness do not necessarily conflict
      with the maintenance of species integrity.

PMID- 24750474
TI  - Temporal and spatial regulation of cAMP signaling in disease: role of cyclic
      nucleotide phosphodiesterases.
AB  - Since its discovery, cAMP has been proposed as one of the most versatile second
      messengers. The remarkable feature of cAMP to tightly control highly diverse
      physiological processes, including metabolism, homeostasis, secretion, muscle
      contraction, cell proliferation and migration, immune response, and gene
      transcription, is reflected by millions of different articles worldwide.
      Compartmentalization of cAMP in space and time, maintained by mainly
      phosphodiesterases, contributes to the maintenance of equilibrium inside the cell
      where one signal can trigger many different events. Novel cAMP sensors seem to
      carry out certain unexpected signaling properties of cAMP and thereby to permit
      delicate adaptations of biologic responses. Measuring space and time events with
      biosensors will increase our current knowledge on the pathophysiology of
      diseases, such as chronic obstructive pulmonary disease, asthma, cognitive
      impairment, cancer, and renal and heart failure. Further insights into the cAMP
      dynamics will help to optimize the pharmacological treatment for these diseases. 

PMID- 24750475
TI  - Reported experiences of bereavement support in Western Australia: a pilot study.
AB  - OBJECTIVE: This article describes the pilot testing of a community survey to
      ascertain the experiences and needs of people who were bereaved 6-24 months
      before the survey. The pilot study aimed to assess the feasibility and
      acceptability of the survey and test the theoretical public health model for
      bereavement support. METHODS: A postal survey was used to collect information
      from clients of three funeral providers in Western Australia in 2012. RESULTS:
      The findings confirmed the feasibility and acceptability of the survey questions.
      The analysis of the demographic characteristics, experience of bereavement and
      satisfaction with support revealed differential needs that align with the
      expectation of low, moderate and high risk, as articulated in the public health
      model. CONCLUSIONS: The data provided tentative empirical support for the public
      health model of bereavement support. This is the first empirical test of this
      model nationally and internationally. IMPLICATIONS: Considering the lack of
      evidence to guide development and allocation of bereavement programs in
      Australia, a larger survey will enable us to determine how the support needs of
      each of the three groups of bereaved people should be serviced. This is important
      for cost-effective and equitable resource allocation.

PMID- 24750476
TI  - Detection of the matrix metalloproteinases MMP-2 and MMP-9 and tissue inhibitors
      of metalloproteinases TIMP-1 and TIMP-2 in llama (Lama glama) oviduct.
AB  - Matrix metalloproteinases (MMPs) and their inhibitors (TIMPs) are involved in
      several reproductive events like oocyte-spermatozoa interaction and semen
      liquefaction. In order to study their role in the llama oviductal reproductive
      process, MMP activity in oviductal fluid (OF) was assayed. Considering that llama
      genome sequences are partially known, a strategy to procure cDNA sequences of MMP
      2, MMP-9, TIMP-1 and TIMP-2 was designed. Afterwards, their expression patterns
      in the different llama oviductal segments were assayed. Gelatine zymograms
      detected 62 and 94 kDa protease activities that matched MMP-2 and pro-MMP-9,
      respectively. Expression pattern analysis showed that MMP and TIMP mRNAs were
      present in ampulla, isthmus, utero-tubal junction (UTJ) and papilla. Altogether,
      these findings support the argument that MMPs/TIMPs are produced in the oviduct
      and secreted into the oviductal lumen. Our results encourage further studies to
      elucidate the role of these proteins in reproductive oviductal events. 

PMID- 24750477
TI  - Apoptosis of cardiomyocytes in children with right ventricular pressure overload
      with and without hypoxemia.
AB  - BACKGROUND: Cardiomyocyte apoptosis has been implicated in ventricular remodeling
      and initiation of cardiac failure. We sought to determine the severity of right
      ventricular (RV) cardiomyocyte apoptosis in cyanotic and acyanotic children with
      RV pressure overload. METHODS: Fourteen patients, seven with tetralogy of Fallot
      (group I) and seven with pulmonary stenosis and ventricular septal defect (group
      II), undergoing open-heart surgery were studied. Right ventricular biopsies were
      examined for cardiomyocyte apoptosis by terminal deoxynucleotide transferase
      mediated dUTP nick-end labeling. The magnitude of cardiomyocyte apoptosis was
      related to preoperative oxygen saturation and postoperative inotrope use and
      hospital stay. RESULTS: Compared with group I patients, group II patients were
      significantly older at operation (p = 0.002) and had a larger body size (p <
      0.01) and higher preoperative oxygen saturation (p = 0.01). The prevalence of
      cardiomyocyte apoptosis in both group I and II patients as a whole was 0.24 +/-
      0.29% (range, 0% to 1.10%). The prevalence was similar between group I (median
      0.30%, range 0% to 1.10%) and group II (median 0.20, range 0% to 0.40%, p =
      0.65). The prevalence of cardiomyocyte apoptosis correlated positively with
      preoperative oxygen saturation on room air (r = -0.69, p < 0.005) and
      postoperative inotrope score (r = 0.67, p = 0.001). A higher postoperative
      inotrope score (r = 0.68, p = 0.001) was associated with a significant longer
      duration of postoperative stay in the hospital. CONCLUSIONS: The prevalence of
      cardiomyocyte apoptosis in the pressure-overloaded right ventricle is related to
      the severity of hypoxia and may have an impact on postoperative course in terms
      of early postoperative use of inotropes and duration of hospital stay.

PMID- 24750478
TI  - Presence of paroxysmal nocturnal hemoglobinuria clones does not exclude inherited
      bone marrow failure syndromes.

PMID- 24750479
TI  - The Christchurch earthquake: dialysis experience and emergency planning.
AB  - On 22 February 2011, a large earthquake struck the Canterbury region in New
      Zealand. There was extensive damage to buildings and infrastructure. The
      following day 42 haemodialysis patients were flown to Auckland where they acutely
      dialysed through the efforts of the Auckland, Waitemata and Counties-Manukau
      dialysis team. Patients and support people were subsequently distributed to a
      designated Upper North Island District Health Board for longer-term ongoing
      dialysis care. The last evacuated haemodialysis patient returned to Christchurch
      on 9 May 2011. Surprisingly there was a dearth of crush syndrome patients
      requiring dialysis. The evacuation and reception of a large number of dialysis
      patients was a novel experience for the New Zealand dialysis community. A
      planning guide for dialysis emergency is available to assist with similar future
      natural disasters. 

PMID- 24750480
TI  - Anaphylaxis following the intravenous administration of continuous erythropoietin
      receptor activator in a haemodialysis patient.

PMID- 24750481
TI  - Probable bullous pemphigoid related to arteriovenous shunt infection.

PMID- 24750482
TI  - The Hajj pilgrimage and surveillance for Middle East Respiratory syndrome
      coronavirus in pilgrims from African countries.

PMID- 24750483
TI  - Prediction of nursery school-aged children who refuse fluoride varnish
      administration in a community setting: a Childsmile investigation.
AB  - BACKGROUND: Young children of pre-school age may find a minimal intervention
      (fluoride varnish application) difficult to tolerate. AIM: To determine the
      significant predictors for refusing a fluoride varnish application from child,
      parental and nurse behaviour factors. DESIGN: Data included videos from 238
      children (52% female, aged 3-5 years) receiving a fluoride varnish application in
      a Scottish nursery school setting. The St Andrews Behavioural Interaction Scheme
      (SABICS) was used for video coding and retrieved child refusal status, initial
      anxious behaviour, and nurse behaviour. A parental survey collected parent's
      dental anxiety [Modified Dental Anxiety Scale (MDAS)] and the child's home
      behaviour [Strengths and Difficulties Questionnaire (SDQ)]. Child demographics,
      dental status, and previous varnish application experience were recorded.
      Multivariate binary logistic regression was applied to predict child refusal of
      the varnish application. RESULTS: The response rate was 79%. Twelve children
      refused. The significant predictors of varnish refusal included initial anxious
      child behaviour (beta = 5.14, P = 0.001), no previous varnish application (beta =
      -3.89, P = 0.04), and no nurse praise (beta = -1.06, P = 0.02). Information
      giving (P = 0.06) and reassurance (P = 0.08) were borderline significant.
      CONCLUSION: Initial anxiety behaviour, previous varnish experience, and not using
      praise by the nursing staff predicted fluoride varnish application refusal.

PMID- 24750484
TI  - Incidence and risk factors of delirium in patients post pancreaticoduodenectomy.
AB  - BACKGROUND: Post-operative delirium is an important and common complication of
      major abdominal surgery characterized by acute confusion with fluctuating
      consciousness. The aim of this study was to establish the incidence of post
      operative delirium in patients undergoing a pancreaticoduodenectomy and to
      determine the risk factors for its development. METHODS: From a prospectively
      maintained database, a retrospective cohort analysis was performed of 50
      consecutive patients who underwent a pancreaticoduodenectomy at the National
      Surgical Centre for Pancreatic Cancer in St. Vincent's University Hospital,
      Dublin and whose entire post-operative stay was in this institution, between July
      2011 and December 2012. Two independent medical practitioners assessed all data
      and delirium was diagnosed according to criteria of the Diagnostic and
      Statistical Manual Disorder (DSM), fourth edition. Univariate and multivariate
      analyses were performed. RESULTS: Seven patients (14%) developed post-operative
      delirium. The median onset was on the second post-operative day. Older age was
      predictive of an increased risk of delirium post-operatively. Those who developed
      delirium had a significantly increased length of stay (LOS) as well as a
      significantly increased risk of developing at least a grade 3 complication
      (Clavien-Dindo classification). CONCLUSION: This study demonstrates that post
      operative delirium is associated with a more complicated recovery after a
      pancreaticoduodenectomy and that older age is independently predictive of its
      development. Focused screening may allow targeted preventative strategies to be
      used in the peri-operative period to reduce complications and costs associated
      with delirium.

PMID- 24750485
TI  - Use of Six Sigma Worksheets for assessment of internal and external failure costs
      associated with candidate quality control rules for an ADVIA 120 hematology
      analyzer.
AB  - BACKGROUND: Quality control (QC) validation is an essential tool in total quality
      management of a veterinary clinical pathology laboratory. Cost-analysis can be a
      valuable technique to help identify an appropriate QC procedure for the
      laboratory, although this has never been reported in veterinary medicine.
      OBJECTIVE: The aim of this study was to determine the applicability of the Six
      Sigma Quality Cost Worksheets in the evaluation of possible candidate QC rules
      identified by QC validation. METHODS: Three months of internal QC records were
      analyzed. EZ Rules 3 software was used to evaluate candidate QC procedures, and
      the costs associated with the application of different QC rules were calculated
      using the Six Sigma Quality Cost Worksheets. The costs associated with the
      current and the candidate QC rules were compared, and the amount of cost savings
      was calculated. RESULTS: There was a significant saving when the candidate 1
      2.5s, n = 3 rule was applied instead of the currently utilized 1-2s, n = 3 rule.
      The savings were 75% per year (L 8232.5) based on re-evaluating all of the
      patient samples in addition to the controls, and 72% per year (L 822.4) based on
      re-analyzing only the control materials. The savings were also shown to change
      accordingly with the number of samples analyzed and with the number of daily QC
      procedures performed. CONCLUSIONS: These calculations demonstrated the importance
      of the selection of an appropriate QC procedure, and the usefulness of the Six
      Sigma Costs Worksheet in determining the most cost-effective rule(s) when several
      candidate rules are identified by QC validation.

PMID- 24750486
TI  - Distinct melanoma types based on reflectance confocal microscopy.
AB  - Distinct melanoma types exist in relation to patient characteristics, tumor
      morphology, histopathologic aspects and genetic background. A new diagnostic
      imaging tool, reflectance confocal microscopy (RCM), allows in vivo analysis of a
      given lesion with nearly histologic resolution while offering a dynamic view of
      the tissue in its 'natural' environment. The aim of this study was to analyse
      cell morphology of consecutive melanomas as they appear on RCM and to correlate
      morphology with tumor and patient characteristics. One hundred melanomas were
      visualized by RCM before excision. Clinical data, confocal features and
      histologic criteria were analysed. Four types of melanomas were identified as
      follows: (i) Melanomas with a predominantly dendritic cell population ('dendritic
      cell melanomas') typically were thin by Breslow index; (ii) Melanomas typified by
      roundish melanocytes were smaller in size than dendritic cell MMs, but thicker by
      Breslow index, and predominantly occurred in patients with a high nevus count;
      (iii) Melanomas characterized by dermal nesting proliferation usually were thick
      by Breslow index at the time of diagnosis, although frequently smaller in size
      compared with the other types; and (iv) combined type melanomas may represent an
      evolution of dendritic cell and/or round cell types. Integration of confocal
      microscopy with clinical and histologic aspects may help in identifying and
      managing distinct tumors.

PMID- 24750487
TI  - Oral health status among 6- to 12-year-old haemophilic children--an educational
      intervention study.

PMID- 24750488
TI  - Host tissues as microhabitats for Wolbachia and quantitative insights into the
      bacterial community in terrestrial isopods.
AB  - Animal-bacterial symbioses are highly dynamic in terms of multipartite
      interactions, both between the host and its symbionts as well as between the
      different bacteria constituting the symbiotic community. These interactions will
      be reflected by the titres of the individual bacterial taxa, for example via host
      regulation of bacterial loads or competition for resources between symbionts.
      Moreover, different host tissues represent heterogeneous microhabitats for
      bacteria, meaning that host-associated bacteria might establish tissue-specific
      bacterial communities. Wolbachia are widespread endosymbiotic bacteria, infecting
      a large number of arthropods and filarial nematodes. However, relatively little
      is known regarding direct interactions between Wolbachia and other bacteria. This
      study represents the first quantitative investigation of tissue-specific
      Wolbachia-microbiota interactions in the terrestrial isopod Armadillidium
      vulgare. To this end, we obtained a more complete picture of the Wolbachia
      distribution patterns across all major host tissues, integrating all three
      feminizing Wolbachia strains (wVulM, wVulC, wVulP) identified to date in this
      host. Interestingly, the different Wolbachia strains exhibited strain-specific
      tissue distribution patterns, with wVulM reaching lower titres in most tissues.
      These patterns were consistent across different host genetic backgrounds and
      might reflect different co-evolutionary histories between the Wolbachia strains
      and A. vulgare. Moreover, Wolbachia-infected females carried higher total
      bacterial loads in several, but not all, tissues, irrespective of the Wolbachia
      strain. Taken together, this quantitative approach indicates that Wolbachia is
      part of a potentially more diverse bacterial community, as exemplified by the
      presence of highly abundant bacterial taxa in the midgut caeca of several A.
      vulgare populations.

PMID- 24750489
TI  - Oral infection with enteropathogenic Escherichia coli triggers immune response
      and intestinal histological alterations in mice selected for their minimal acute
      inflammatory responses.
AB  - Enteropathogenic Escherichia coli (EPEC), a leading cause of infant diarrhea, is
      an important public health problem in Brazil and other developing countries. In
      vitro assays of bacterial adhesion to cultured cells are important tools for
      studying bacterial pathogenicity but do not reproduce all the events that occur
      in natural infections. In this study, the effects of oral infection with EPEC on
      mice selected for their minimal acute inflammatory response (AIR min) were
      evaluated. Mice were orally infected with EPEC and variations in body weight,
      bacterial shedding and antibody production observed. The infected animals
      developed seric and secretory anti-EPEC antibodies; however, neither mortality
      nor diarrhea was observed. Light microscopy of their intestines demonstrated
      histological modifications that were not present in controls. However, electron
      microscopy did not show bacteria attached to the intestinal epithelia to form
      attaching and effacing lesions, characteristic of EPEC in humans. The bacteria
      were detected in Peyer's patches and intestinal contents up to 5 hr post
      infection. When human anti-EPEC secretory immunoglobulin A or avian
      immunoglobulin Y antibodies were administered to infected animals, they developed
      minor histological alterations compared with non-treated animals. In summary, it
      was found that EPEC triggers immune responses and intestinal histological
      alterations but does not produce evidence of diarrheal disease in mice infected
      by the oral route. This study of EPEC experimental infection provides a better
      understanding of the effects of antibodies on bacterial infections and may
      provide a suitable model for the design and testing of immunobiological products
      for active or passive immunization.

PMID- 24750490
TI  - Effects of chronic oestradiol, progesterone and medroxyprogesterone acetate on
      hippocampal neurogenesis and adrenal mass in adult female rats.
AB  - Both natural oestrogens and progesterone influence synaptic plasticity and
      neurogenesis within the female hippocampus. However, less is known of the impact
      of synthetic hormones on hippocampal structure and function. There is some
      evidence that the administration of the synthetic progestin, medroxyprogesterone
      acetate (MPA) is not as beneficial as natural progesterone and can attenuate
      oestrogen-induced neuroprotection. Although the effects of oestradiol have been
      well studied, little is known about the effects of natural and synthetic
      progestins alone and in combination with oestradiol on adult neurogenesis in
      females. In the present study, we investigated the effects of chronic oestradiol,
      progesterone, MPA and the co-administration of each progestin with oestradiol on
      neurogenesis within the dentate gyrus of adult ovariectomised female rats. Twenty
      four hours after a bromodeoxyuridine (BrdU; 200 mg/kg) injection, female rats
      were repeatedly administered either progesterone (1 or 4 mg), MPA (1 or 4 mg),
      oestradiol benzoate (EB), progesterone or MPA in combination with EB (10 MUg), or
      vehicle for 21 days. Rats were perfused on day 22 and brain tissue was analysed
      for the number of BrdU-labelled and Ki67 (an endogenous marker of cell
      proliferation)-expressing cells. EB alone and MPA + EB significantly decreased
      neurogenesis and the number of surviving BrdU-labelled cells in the dorsal region
      of the dentate gyrus, independent of any effects on cell proliferation.
      Furthermore, MPA (1 and 4 mg) and MPA + EB treated animals had significantly
      lower adrenal/body mass ratios and reduced serum corticosterone (CORT) levels. By
      contrast, progesterone + EB treated animals had significantly higher adrenal/body
      mass ratios and 1 mg of progesterone, progesterone + EB, and EB significantly
      increased CORT levels. The results of the present study demonstrate that
      different progestins alone and in combination with oestradiol can differentially
      affect neurogenesis (via cell survival) and regulation of the hypothalamic
      pituitary-adrenal axis. These findings have implications for women using hormone
      replacement therapies with MPA for both neuroprotection and stress-related
      disorders.

PMID- 24750491
TI  - Possible association between stem-like hallmark and radioresistance in human
      cervical carcinoma cells.
AB  - AIM: We aimed to investigate the possibility of an association between a stem
      like hallmark and radiotherapeutic sensitivity in human cervical carcinoma cells.
      MATERIAL AND METHODS: Side-population (SP) cells and non-SP (NSP) cells in HeLa
      cells were isolated using flow cytometry and Hoechst 33342 efflux. We performed
      Western blot analysis to evaluate the expression of stem cell markers (CXCR4,
      Oct3/4, CD133, and SOX2) and apoptosis markers after irradiation. In addition, SP
      and NSP cells were injected into nude mice and we assessed subcutaneous tumor
      formation. To examine tolerance of irradiation, colony formation and apoptosis
      change were confirmed in the SP and NSP cells. RESULTS: SP cells showed a higher
      expression of CXCR4, Oct3/4, CD133, and SOX2 than NSP cells. The colony size of
      SP cells cultured on non-coated dishes was larger than that of NSP cells, and NSP
      cells were easily induced to undergo apoptosis. SP cells tended to form spheroids
      and showed a higher level of tumorigenicity compared with NSP cells. In addition,
      nude mice inoculated with SP cells showed greater tumor growth compared with NSP
      cells. SP cells showed a higher tumorigenicity and lower apoptotic potential,
      leading to enhanced radiotolerance. CONCLUSION: Tumor SP cells showed higher
      level stem-cell-like characters and radioresistance than NSP cells. SP cells may
      be useful for new therapeutic approaches for radiation-resistant cervical cancer.

PMID- 24750492
TI  - Trends and recurrence of stillbirths in NSW.
AB  - OBJECTIVE: To examine the trend in stillbirth rates adjusted for the trends in
      the maternal risk profile, and to use local data to estimate the stillbirth
      recurrence risk. METHODS: Linked hospital, birth and perinatal death review data
      were used to identify risk factors and stillbirths among women giving birth to
      singletons in NSW between 2001 and 2009. Logistic regression models were
      developed to predict stillbirth rates based on the changes in the maternal
      population. RESULTS: Between 2001 and 2009 there were 3,449 stillbirths (4.4 per
      1,000 births), with no significant change in rate overall (p=0.6) or across older
      gestational age categories (26-33 weeks p=0.67, >=34 weeks p=0.36), and a slight
      increase at <26 weeks (p=0.01). However, when changes in the maternal population
      were taken into account, there was a significant increase in stillbirths at <26
      weeks (p<0.001). Women with a stillbirth in a first pregnancy were at increased
      risk of stillbirth in their second pregnancy (4.3 95%CI 2.4-7.7). CONCLUSION:
      There has been no decline in the stillbirth rate in NSW in recent years, which,
      at late gestations, may be accounted for by changes in the maternal population.
      At early gestations, there has been an increase in stillbirths where a decrease
      in rate may be expected based on the maternal population. IMPLICATIONS: Further
      focus on addressing risk factors for stillbirths is needed to ensure continued
      progress is made in reducing stillbirths.

PMID- 24750493
TI  - The AMPA receptor antagonist perampanel is a new hope in the treatment for
      epilepsy.
AB  - Perampanel is a novel drug recently approved as adjunctive therapy in epileptic
      patients aged 12 years and older who have drug-resistant partial epilepsy with
      and without secondary generalization. Pharmacological researches revealed that
      perampanel reduces neuronal excitability by a non-competitive antagonistic
      activity against the ionotropic alpha-amino-3-hydroxy-5-methyl-4-isoxazole
      propionic acid (AMPA) receptors causing modulation of glutamatergic
      neurotransmission. The pharmacological profile of the drug showed complete
      absorption following oral administration, and extensive metabolism in the liver
      by oxidation followed by glucuronidation with an elimination half-life of
      approximately 53-165 h (average: 105 h), allowing once-daily administration.
      Randomized placebo-controlled trials demonstrated an effective dose range of the
      drug, between 4 and 12 mg/day, to significantly reduce seizure frequency in
      patients with partial-onset seizure that are pharmacoresistant with a favorable
      tolerability profile. The most frequent adverse events of the drug reported in
      phase III clinical trials were dizziness, somnolence, fatigue, and headache.
      However, the data raised from the studies can give a hope that perampanel offers
      a valuable option as an adjuvant therapy for pharmacoresistant partial-onset and
      secondarily generalized seizures.

PMID- 24750495
TI  - Sutureless repair of ventricular free wall rupture.

PMID- 24750494
TI  - Involvement of histamine in endothelium-dependent relaxation of mesenteric
      lymphatic vessels.
AB  - OBJECTIVES: The knowledge of the basic principles of lymphatic function, still
      remains, to a large degree, rudimentary and will require significant research
      efforts. Recent studies of the physiology of the MLVs suggested the presence of
      an EDRF other than NO. In this study, we tested the hypothesis that lymphatic
      endothelium-derived histamine relaxes MLVs. METHODS: We measured and analyzed
      parameters of lymphatic contractility in isolated and pressurized rat MLVs under
      control conditions and after pharmacological blockade of NO by L-NAME (100 MUM)
      or/and histamine production by alpha-MHD (10 MUM). Effectiveness of alpha-MHD was
      confirmed immunohistochemically. We also used immunohistochemical labeling and
      Western blot analysis of the histamine-producing enzyme, HDC. In addition, we
      blocked HDC protein expression in MLVs by transient transfection with vivo
      morpholino oligos. RESULTS: We found that only combined pharmacological blockade
      of NO and histamine production completely eliminates flow-dependent relaxation of
      lymphatic vessels, thus confirming a role for histamine as an EDRF in MLVs. We
      also confirmed the presence of HDC and histamine inside lymphatic endothelial
      cells. CONCLUSIONS: This study supports a role for histamine as an EDRF in MLVs.

PMID- 24750496
TI  - Survey of point-of-care instrumentation, analysis, and quality assurance in
      veterinary practice.
AB  - BACKGROUND: While there have been ASVCP meeting discussions regarding quality
      assurance plans and lack thereof for in-clinic analyzers, there are little
      published data regarding in-clinic quality assurance and control practices.
      OBJECTIVES: The purpose of this study was the identification of the common
      equipment used in hematologic, biochemical, urinalysis, and other testing, and
      assessment of quality control and assurance programs currently being performed in
      clinic. METHODS: All members of the Veterinary Information Network (VIN) were
      solicited to participate in an online survey between July and September 2007.
      RESULTS: In total, 452 complete or partial responses were received. Eighty-nine
      percent of respondents (361/404) said that veterinary technicians (unlicensed,
      licensed, and registered) performed the majority of analyses. Eighty-eight
      percent (366/417) of respondents performed some quality assurance on their
      laboratory equipment, most commonly on chemistry (91%, 324/357), and hematology
      (84%, 292/347) analyzers, and least commonly on fecal analyses (57%, 148/260) and
      ELISA assays (25%, 65/256). Ignorance of how to perform quality assurance was the
      most commonly stated reason (49%, 25/51) for lack of a quality assurance program.
      The majority of practices (316/374) utilized manufacturer-provided reference
      intervals without further adjustment or assessment. Roughly one-third of
      respondents (126/374) used reference intervals from textbooks, which is
      discouraged by ASVCP guidelines. CONCLUSIONS: This study found that the majority
      of respondents were not in compliance with ASVCP guidelines, illustrating the
      need for improved education of technical staff, veterinary students, and
      veterinarians regarding limitations of in-clinic laboratory equipment and the
      importance of regular quality control, maintenance, training, and reference
      interval development.

PMID- 24750497
TI  - Use of factor VIII after inhibitor clearance in patients with moderate
      haemophilia A: a case series.

PMID- 24750498
TI  - Direct comparison of the effects of slow freezing and vitrification on late
      blastocyst gene expression, development, implantation and offspring of rabbit
      morulae.
AB  - This study aimed to assess the effect of different cryopreservation procedures
      (slow freezing vs vitrification) on the gene expression in pre-implantation
      embryos and its implication in post-implantation embryo losses in rabbit. For
      this purpose, rabbit morulae were recovered at Day 3 of development, frozen or
      vitrified and transferred to recipients. Then, embryos were recovered on Day 3
      post-transfer (Day 6 of development) or kept until the end of gestation. Apart
      from the gene expression analysis at Day 6, we also studied the pre-implantatory
      and foetal development ability of both cryopreserved embryo types by evaluating
      late blastocyst development at Day 6, embryo implantation at Day 11 post-transfer
      (Day 14 of development) and birth rate. We reported that slow freezing and
      vitrification have similar effects on embryo developmental ability till Day 6,
      but the distribution of losses changes during implantation and further
      development. These similarities at Day 6 of development were also reflected in
      gene expression patterns, and transcriptome analysis showed no differences
      between frozen and vitrified embryos. Our results confirm that vitrification
      provides better implantation and birth rates than slow freezing for rabbit
      embryos. As both the techniques are commonly used in human assisted reproduction,
      further experiments must be conducted to clarify the causes that may hinder
      foetal development and their impact on adulthood. 

PMID- 24750499
TI  - Access to mobile communications by older people.
AB  - AIM: To investigate how older people effectively identify, select and learn to
      use mobile communications technologies to enhance communication and safety, and
      support independent living. METHODS: One hundred and fifty-three older South
      Australians participated in a purpose-designed survey questionnaire. RESULTS:
      Older people relied on family and friends for information and advice (76%), and
      their children's assistance with buying (45%) and learning to use (48%) new
      technology. The most preferred learning method was face-to-face training (56%).
      Less than half (44%) were interested in trying out new designs/applications,
      functions and capabilities that could assist with independent living. The highest
      need was for personal security and emergencies (88%). CONCLUSIONS: Findings
      suggest that the family and friends of older people play an important role in
      identifying, selecting and learning to use mobile communication technologies. The
      safety and emergency capabilities of mobile communications technologies were more
      important than having functions that could assist with independent living.

PMID- 24750500
TI  - Congener diversity, topographic heterogeneity and human-assisted dispersal
      predict spread rates of alien herpetofauna at a global scale.
AB  - Understanding the factors that determine rates of range expansion is not only
      crucial for developing risk assessment schemes and management strategies for
      invasive species, but also provides important insight into the ability of species
      to disperse in response to climate change. However, there is little knowledge on
      why some invasions spread faster than others at large spatiotemporal scales.
      Here, we examine the effects of human activities, species traits and
      characteristics of the invaded range on spread rates using a global sample of
      alien reptile and amphibian introductions. We show that spread rates vary
      remarkably among invaded locations within a species, and differ across
      biogeographical realms. Spread rates are positively related to the richness of
      native congeneric species and human-assisted dispersal in the invaded range but
      are negatively correlated with topographic heterogeneity. Our findings highlight
      the importance of environmental characteristics and human-assisted dispersal in
      developing robust frameworks for predicting species' range shifts.

PMID- 24750501
TI  - Repeated landmass reformation limits diversification in the widespread littoral
      zone mosquito Anopheles sundaicus sensu lato in the Indo-Oriental Region.
AB  - Southeast Asia harbours abundant biodiversity, hypothesized to have been
      generated by Pliocene and Pleistocene climatic and environmental change.
      Vicariance between the island of Borneo, the remaining Indonesian archipelago and
      mainland Southeast Asia caused by elevated sea levels during interglacial periods
      has been proposed to lead to diversification in the littoral zone mosquito
      Anopheles (Cellia) sundaicus (Rodenwaldt) sensu lato. To test this
      biogeographical hypothesis, we inferred the population history and assessed gene
      flow of A. sundaicus s.l. sampled from 18 populations across its pan-Asian
      species range, using sequences from mitochondrial cytochrome c oxidase subunit 1
      (CO1), the internal transcribed spacer 2 (ITS2) and the mannose phosphate
      isomerase (Mpi) gene. A hypothesis of ecological speciation for A. sundaicus
      involving divergent adaptation to brackish and freshwater larval habitats was
      also previously proposed, based on a deficiency of heterozygotes for Mpi allozyme
      alleles in sympatry. This hypothesis was not supported by Mpi sequence data,
      which exhibited no fixed differences between brackish and freshwater larval
      habitats. Mpi and CO1 supported the presence of up to eight genetically distinct
      population groupings. Counter to the hypothesis of three allopatric species,
      divergence was often no greater between Borneo, Sumatra/Java and the Southeast
      Asian mainland than it was between genetic groupings within these landmasses. An
      isolation-with-migration (IM) model indicates recurrent gene flow between the
      current major landmasses. Such gene flow would have been possible during glacial
      periods when the current landmasses merged, presenting opportunities for
      dispersal along expanding and contracting coastlines. Consequently, Pleistocene
      climatic variation has proved a homogenizing, rather than diversifying, force for
      A. sundaicus diversity. 

PMID- 24750502
TI  - Tyrosine hydroxylase in the olfactory system, forebrain and pituitary of the
      Indian major carp, Cirrhinus cirrhosus: organisation and interaction with
      neuropeptide Y in the preoptic area.
AB  - Dopamine (DA) inhibits, whereas gonadotrophin-releasing hormone (GnRH)
      stimulates, luteinisiing (LH) cells in the pituitary of some but not all
      teleosts. A reduction in the hypophysiotropic dopaminergic tone is necessary for
      the stimulatory effect of GnRH on LH cells. Neuropeptide Y (NPY) has emerged as
      one of the potent, endogenous agent that modulates LH secretion directly or
      indirectly via GnRH. Involvement of NPY in the regulation of hypophysiotropic DA
      neurones, however, is not known, but there is good evidence suggesting an
      interaction in the mammalian hypothalamus. DA neurones, identified by tyrosine
      hydroxylase (TH)-immunoreactivity, were observed widely throughout the brain of
      the Indian major carp, Cirrhinus cirrhosus. The granule cells and ganglion cells
      of terminal nerve in the olfactory bulb, and cells in ventral telencephalon and
      preoptic area (POA) showed conspicuous TH immunoreactivity. In the POA, the
      nucleus preopticus periventricularis (NPP), divisible into anterior (NPPa) and
      posterior (NPPp) components, showed prominent TH-immunoreactivity. The majority
      of TH neurones in NPPa showed axonal extensions to the pituitary and were closely
      associated with LH cells. The NPPa also appeared to be the site for intense
      interaction between NPY and DA because it contains a rich network of NPY fibres
      and few immunoreactive cells. Approximately 89.7 +/- 1.5% TH neurones in NPPa
      were contacted by NPY fibres. Superfused POA slices treated with a NPY Y2 
      receptor agonist, NPY 13-36 resulted in a significant (P < 0.001) reduction in TH
      immunoreactivity in NPPa. TH neurones in NPPa did not respond to NPY Y1 -receptor
      agonist, [Leu(31) , Pro(34) ] Neuropeptide Y treatment. We suggest that, by
      inhibiting DAergic neurones in NPPa via Y2 -receptors, NPY may contribute to the
      up-regulation of the GnRH-LH cells axis. The microcircuitry of DA and NPY and
      their interaction in NPPa might be a crucial component in the central regulation
      of LH secretion in the teleosts.

PMID- 24750503
TI  - Polypoid endometriosis of the ovary mimicking ovarian carcinoma dissemination: a
      case report and literature review.
AB  - Polypoid endometriosis is a rare type of endometriosis. We report a case of
      polypoid endometriosis of the ovary mimicking ovarian carcinoma with peritoneal
      dissemination. Computed tomography and magnetic resonance imaging showed a left
      ovarian endometriotic cyst containing several nodules in the cystic wall that
      displayed enhancement, and pelvic nodules on the right ovary. A preoperative or
      intraoperative diagnosis to avoid the unnecessary extended operation is important
      for such disease. Retrospective magnetic resonance imaging analysis identified a
      peculiar finding for polypoid endometriosis: all solid nodules had a round and
      smooth shape and displayed a low-signal-intense marginal edge on T2-weighted
      images, suggesting that this is an important finding for differentiating polypoid
      endometriosis from ovarian carcinoma arising from endometriosis. 

PMID- 24750504
TI  - ALK gene aberrations and the JUN/JUNB/PDGFR axis in metastatic NSCLC.
AB  - Anaplastic lymphoma kinase (ALK) gene aberrations are found in several tumor
      types including anaplastic large cell lymphoma (ALCL) and non-small cell lung
      cancer (NSCLC). Crizotinib, an inhibitor of ALK-fusion proteins, has shown
      clinical activity, but resistance mechanisms limit long-lasting disease control.
      It has been shown that ALK-NPM fusion upregulates platelet-derived growth factor
      receptor beta (PDGFRB) via JUN and transcription factor Jun B (JUNB) in ALCL.
      PDGFRB inhibition has been identified as therapy option for ALK-positive ALCL.
      Here, we investigated the ALK/JUN/JUNB/transcription factor Jun C (JUNC)/PDGFR
      axis in metastatic NSCLC with regard to ALK aberrations. We performed
      immunohistochemical analysis of platelet-derived growth factor receptor alpha
      (PDGFRA), PDGFRB, JUNB and JUNC expression in formalin-fixed, paraffin-embedded
      specimens of 15 NSCLC brain metastases (5 ALK translocations, 3 of them involving
      EML4, 5 ALK amplifications, 5 without ALK aberrations). We did not find a
      statistically significant difference in expression of PDGFRA, PDGFRB, JUNB or
      JUNC in tumor samples with normal ALK status, ALK amplification or ALK
      translocations (Kruskal-Wallis test p > 0.05). Interestingly, PDGFRB was not
      expressed in tumor cells (but in vascular and stromal cells) in any of our cases.
      Our data argue against PDGFRB activation in association with ALK gene aberrations
      in metastatic NSCLC and thus seem to imply differential pathobiological roles of
      ALK alterations in lung cancer and lymphoma, possibly depending on different
      fusion partner genes. These results may be relevant for targeted therapies, as
      they indicate that inhibition of PDGFRB in ALK translocated NSCLC seems to be no
      therapeutic opportunity. 

PMID- 24750506
TI  - Exercise despite pain--breast cancer patient experiences of muscle and joint pain
      during adjuvant chemotherapy and concurrent participation in an exercise
      intervention.
AB  - Chemotherapy-related pain is a well-known side effect in cancer patient receiving
      chemotherapy. However, limited knowledge exists describing whether exercise
      exacerbates existing pain. Aim of the research was to explore muscle and joint
      pain experienced by women with breast cancer receiving adjuvant chemotherapy with
      epirubicin and cyclophosphamide followed by docetaxel and factor support and
      concurrently participating in an exercise intervention. The study used individual
      semi-structured interviews (pre- and post-intervention). Fifteen women were
      interviewed. The multimodal group intervention comprised supervised training:
      high-intensity cardiovascular, heavy resistance and relaxation, massage and body
      awareness (9 h weekly, 6 weeks). The analysis revealed five categories: Abrupt
      pain - a predominant side effect, cogitated pain management, the adapted
      training, non-immediate exacerbation of pain and summarised into the essence of
      chemotherapy related muscle and joint pain in exercise breast cancer patients;
      exercise despite pain. Findings indicate that the patients' perception of sudden
      onset of chemotherapy-related muscle and joint pain was not aggravated by
      training. Pain intensity peaked between 2 and 9 days after chemotherapy and is
      described to be stabbing pain with a feeling of restlessness in the body. The
      patients demonstrated a high adherence rate to the exercise intervention caused
      by their own willpower and camaraderie of the group. 

PMID- 24750507
TI  - Breast density, supplemental screening, and a streamlined approach to discussion
      between a patient and her doctor--a novel, efficient approach.

PMID- 24750505
TI  - The development and assessment of biological treatments for children.
AB  - The development of biological agents with specific immunological targets has
      revolutionized the treatment of a wide variety of paediatric diseases where
      traditional immunosuppressive agents have been partly ineffective or intolerable.
      The increasing requirement for pharmaceutical companies to undertake paediatric
      studies has provided impetus for studies of biologics in children. The assessment
      of biological agents in children to date has largely relied upon randomized
      controlled trials using a withdrawal design, rather than a parallel study design.
      This approach has been largely used due to ethical concerns, including use of
      placebo treatments in children with active chronic disease, and justified on the
      basis that treatments have usually already undergone robust assessment in related
      adult conditions. However, this study design limits the reliability of the data
      and can confuse the interpretation of safety results. Careful ongoing monitoring
      of safety and efficacy in real-world practice through national and international
      biologics registries and robust reporting systems is crucial. The most commonly
      used biological agents in children target tumour necrosis factor-alpha,
      interleukin-1, interleukin-6 and cytotoxic lymphocyte-associated antigen-4. These
      agents are most frequently used in paediatric rheumatic diseases. This review
      discusses the development and assessment of biologics within paediatric
      rheumatology with reference to the lessons learned from use in other
      subspecialties. 

PMID- 24750508
TI  - Diagnostic performance of CT attenuation values of focal 18F-FDG avid breast
      lesions detected on whole-body PET-CT in postoperative breast cancer patients.
AB  - To assess whether CT attenuation values help in differentiating benign from
      malignant etiology of focal (18) F-FDG avid breast lesions detected on whole-body
      PET/CT exam in postoperative breast cancer patients. Institutional review board
      approval and waived informed consent were obtained for this HIPAA-compliant
      retrospective study. Between January 2009 and July 2011, a total of 85 patients
      had 97 focal (18) F-FDG avid breast lesions on whole-body PET/CT. Of these, 54
      (56%) lesions were biopsy-proven primary invasive breast carcinoma that had not
      undergone treatment at the time of PET/CT, 35 (36%) were benign lesions, and 8
      were locally recurrent breast carcinoma. Mean attenuation values were
      retrospectively measured in Hounsfield units (HU) for the correlative lesion on
      the CT portion of the exam. Receiver-operating characteristic curves (ROC) were
      calculated to determine the optimal cutoff values of HU that would best
      discriminate between benign and malignant lesions. Interobserver agreement for
      measured mean attenuation values was assessed by calculating the intraclass
      correlation coefficient (ICC). Mean HU for the benign lesions group and the local
      recurrence lesions group was -11.0 +/- 30.3 versus 32.9 +/- 6.87 (p < 0.0002).
      ROC curve analysis comparing benign breast lesions to local recurrence lesions
      found an optimal cutoff value of 17 HU (area under curve = 0.982, p < 0.0001,
      Sensitivity = 100%, Specificity = 89%). ICC with regard to interobserver
      agreement in measuring the mean HU of the benign lesions was 0.84 (95% confidence
      interval 0.64-0.93) and for the malignant lesions was 0.88 (95% confidence
      interval 0.77-0.94). A CT attenuation threshold value of less than 17 HU suggests
      benign etiology of focal (18) FDG avid breast lesions in postoperative breast
      cancer patients. If confirmed by additional studies, these findings may provide
      additional information to guide the treating physician regarding decisions for
      supplementary imaging or the need to biopsy. 

PMID- 24750509
TI  - Role of preoperative breast MRI in ductal carcinoma in situ for prediction of the
      presence and assessment of the extent of occult invasive component.
AB  - Ductal carcinoma in situ (DCIS) is a common neoplasm that may be associated with
      focal invasive breast cancer lesions. The aim of our study was to evaluate the
      role of preoperative magnetic resonance imaging (MRI) in determining occult
      invasive presence and disease extent in patients with preoperative diagnosis of
      pure DCIS. We analyzed 125 patients with postoperative pure DCIS (n = 91) and
      DCIS plus invasive component (n = 34). Diagnostic mammography (MRX) showed a size
      underestimation rate of 30.4% while MRI showed an overestimation rate of 28.6%.
      Comparing the mean absolute error between preoperative MRI and MRX evaluations
      and final disease extent, MRI showed an improved accuracy of 51.2%. In our
      analysis preoperative breast MRI showed a better accuracy in predicting
      postoperative pathologic extent of disease, adding strength to the growing
      evidences that preoperative MRI can lead to a more appropriate management of DCIS
      patients. 

PMID- 24750510
TI  - Hypofractionated radiation therapy for early stage breast cancer: outcomes,
      toxicities, and cost analysis.
AB  - A French prospective randomized trial comparing whole breast radiotherapy with 45
      Gy in 25 fractions versus 23 Gy in four fractions demonstrated equivalent 5-year
      local control and survival. On the basis of this data, we offer the
      hypofractionated regimen to women who refuse to undergo standard radiotherapy. We
      report our outcomes and a cost analysis. Between 2000 and 2012, 84 patients
      participated in this IRB-approved study and underwent whole breast radiation to
      23 Gy in four fractions. Local control and survival were analyzed using the
      Kaplan-Meier method. Acute toxicities and overall long-term cosmetic results were
      assessed. Costs were estimated from 2012 Medicare reimbursement data and compared
      to costs from standard courses of 25 and 16 fractions. All 84 patients are
      included in this report. Median age was 83 (range 42-98). Most patients had stage
      I (80%), hormone receptor positive (90%) breast cancer. Fifty-eight patients
      (69%) were treated prone and 26 (31%) supine. At a median follow-up of 3 years,
      one local recurrence has occurred, of ductal carcinoma in situ histology. Among
      the 13 patients deceased, two died of metastatic breast cancer. Five-year
      actuarial local control is 99%, breast cancer-specific survival is 98%, and
      overall survival is 79%. Toxicities were limited to grade 1 dermatitis in 32
      patients (38%) and grade 2 fatigue in three (4%). Sixty-three patients (75%)
      reported good or excellent cosmetic outcome at their last follow-up. Collected
      Medicare reimbursement was $4,798 for the hypofractionated course. Compared to
      the projected reimbursement of standard regimens, $10,372 for 25 fractions and
      $8,382 for 16 fractions, it resulted in a difference of $5,574 and $3,584,
      respectively. At a follow-up of 3 years, this hypofractionated regimen appears to
      be a promising approach, primarily for elderly women who are unable to undergo
      longer treatment courses but have indications for whole breast radiotherapy. 

PMID- 24750511
TI  - Risk factors for complications following breast reduction: results from a
      randomized control trial.
AB  - Reduction mammoplasty has been shown to benefit physical, physiological, and
      psycho-social health. However, there are some recognized complications. It would
      be beneficial if one could identify and modify the factors which increase the
      rate of complications. To determine the effects of resection weight, BMI, age,
      and smoking on complication rates following reduction mammoplasty. Data were
      gathered as a part of randomized control trial (RCT) examining psycho-social &
      QOL benefits of reduction mammoplasty. Sixty-seven consecutive female patients
      referred to either the Hull Breast Unit or Hull Plastic and Reconstructive
      Surgery Unit and underwent Inferior pedicle reduction mammoplasty were recruited.
      Complications were recorded prospectively. Data gathered included resection
      weight, BMI, age, and smoking status. Smoking status was categorized into
      current; ex; and never. Prospective records of all complications were noted. SPSS
      was used for purposes of statistical analysis. Of the 67 patients, 16 (23.9%) had
      complications. Higher resection weight, increased BMI, and older age are
      associated with high rate of complications with significance reaching p-values of
      p < 0.001, p = 0.034, and p = 0.004, respectively. Among the 67 women who had
      surgery, nine (13.4%) were current smokers, 20 (29.9%) were ex-smokers, and 38
      (56.7%) never smoked. The incidence of complications was highest among current
      smokers and lowest among those who had never smoked. When comparing the current
      smokers with those who are not currently smoking, there is a 37% difference in
      the occurrence of complication. The chi-squared test shows that this is a
      significant difference (p < 0.01) at the 99% confidence interval. Higher
      resection weight, increased BMI, older age, and smoking are risk factors for
      complications. Patients should be adequately counseled about losing weight and
      stopping smoking. 

PMID- 24750512
TI  - Oncoplastic mammoplasty as a strategy for reducing reconstructive complications
      associated with postmastectomy radiation therapy.
AB  - Given the high complication rates in patients who require radiation therapy (XRT)
      after mastectomy and immediate reconstruction, and the low local recurrence rates
      following neo-adjuvant chemotherapy and breast conservation therapy, we sought to
      determine if using neo-adjuvant chemotherapy and oncoplastic mammoplasty as an
      alternative to mastectomy and immediate reconstruction is an effective strategy
      for reducing complication rates in the setting of XRT. A prospectively maintained
      data base was queried for patients who received neo-adjuvant chemotherapy and XRT
      between 2001 and 2010 and underwent either oncoplastic mammoplasty or mastectomy
      with immediate reconstruction. Rates of postoperative complications between
      groups were compared using Fisher's exact test. Outcomes from 37 patients who
      underwent oncoplastic mammoplasty were compared to 64 patients who underwent
      mastectomy with immediate reconstruction. Mean follow-up was 33 months (range 4
      116 months). Rates of postoperative complications, including unplanned operative
      intervention for a reconstructive complication (2.7% versus 37.5%, p < 0.001),
      skin flap necrosis (10.8% versus 29.7%, p = 0.05), and infection (16.2% versus
      35.9, p = 0.04) were significantly higher in the mastectomy group. Overall, 45.3%
      of patients who underwent mastectomy developed at least one breast complication,
      compared to 18.9% of patients who underwent oncoplastic mammoplasty (p = 0.01).
      If XRT is indicated after mastectomy, attempts should be made to achieve breast
      conservation through the use of neo-adjuvant therapy and oncoplastic surgery in
      order to optimize surgical outcomes. Breast conservation with oncoplastic
      reconstruction does not compromise oncologic outcome, but significantly reduces
      complications compared to postmastectomy reconstruction followed by XRT. 

PMID- 24750513
TI  - Tattoo ink within lymph nodes: a possible clinical mimicker of abnormal
      calcifications.

PMID- 24750514
TI  - Ethnicity disparities of breast cancer within an insured population.

PMID- 24750515
TI  - Distinct protein expression and activity of transglutaminases found in different
      epidermal tumors.
AB  - We investigated protein expression and in situ activity of transglutaminases
      (TGs) in normal skin and various epidermal neoplasms. In normal skin, TG1 protein
      expression and TG activity were found at keratinocyte cell membranes in upper
      epidermis and granular layer, respectively. In seborrhoeic keratosis, TG1 protein
      was expressed evenly throughout tumors, while TG activity increased in gradient
      fashion from lower tumor area to cornified layer. In squamous cell carcinoma, TG1
      protein was expressed at inner side of cell membranes, whereas TG activity was
      found in cytoplasm predominantly at horn pearls. In basal cell carcinoma, weak TG
      activity was found in cytoplasm of all tumor cells without the presence of TG1
      protein. Immunoblotting and in situ activity assays using specific substrate
      peptides confirmed that TG2, but not TG1, contributed to the TG activity. These
      results suggested that different expression and activation of TGs may contribute
      to characteristics of the skin tumors.

PMID- 24750517
TI  - Reply to letter to the editor.

PMID- 24750516
TI  - Policy challenges facing integrated community case management in Sub-Saharan
      Africa.
AB  - OBJECTIVE: To report an in-depth analysis of policy change for integrated
      community case management of childhood illness (iCCM) in six sub-Saharan African
      countries. We analysed how iCCM policies developed and the barriers and
      facilitators to policy change. METHODS: Qualitative retrospective case studies
      drawing from document reviews, semi-structured interviews and in-country
      validation workshops were conducted in Burkina Faso, Kenya, Malawi, Mali,
      Mozambique and Niger. These countries were selected to maximise variation in iCCM
      policy status, community health worker (CHW) models and different African
      regions. RESULTS: Country iCCM policies evolved in an ad hoc fashion, but were
      substantially influenced by the history of primary health care and the nature of
      CHW programmes. Technical officers within Ministries of Health led iCCM policy
      change with support from international donors, but neither communities nor
      political leadership was mobilised. Concerns about achieving the Millennium
      Development Goals, together with recognition of the shortcomings of existing
      child health programmes, led to the adoption of iCCM policies. Availability of
      external financing played a critical role in facilitating policy change.
      CONCLUSIONS: iCCM policy change has been promoted by international agencies, but
      national governments have struggled to align iCCM with country health systems.
      Greater investment is needed in tailoring global policy initiatives to match
      country needs. High-level, political ownership of iCCM policies could facilitate
      policy change, as could clearer strategies for ensuring the long-term
      sustainability of such policies.

PMID- 24750519
TI  - Recurrent immature teratoma of the ovary with long-term disease-free interval.
AB  - Grade 3 immature teratoma of the ovary is rare and has a poor prognosis due to
      early recurrence. This report describes a case of grade 3 immature teratoma of
      the ovary that recurred 16 years after the last treatment. The patient underwent
      abdominal simple total hysterectomy, bilateral salpingo-oophorectomy, pelvic-para
      aortic lymphadenectomy, and adjuvant chemotherapy under the diagnosis of grade 3
      immature teratoma of the ovary when she was 15 years old, and complete remission
      was achieved. Sixteen years after the initial treatment, the tumor relapsed in
      her liver and pleura. She was treated by 10 courses of tri-weekly paclitaxel and
      carboplatin, and was alive with stable disease for 12 months after the disease
      relapse. After 1 year, the tumor progressed, and she died 16 months after the
      relapse. This is the first report of grade 3 immature teratoma of the ovary that
      relapsed more than 5 years after the prior treatment. 

PMID- 24750520
TI  - Patients' strategies to deal with their situation at an emergency department.
AB  - INTRODUCTION: The care in the emergency department (ED) is often characterised by
      high standards of efficiency and rapid treatment and the encounter between
      patient and staff can be described as both short and fragmented. Research within
      this field has mostly been performed with quantitative measurements and patients
      are both satisfied and vulnerable in their care at an ED. There is a lack of
      qualitative studies about patient's strategies to deal with their situation. AIM:
      The aim was to describe patient's strategies for dealing with their situation at
      an ED. METHODS: Secondary analysis has been made of 13 qualitative interviews
      grounded in a lifeworld perspective. The interviews were analysed by qualitative
      content analysis. RESULTS: The results showed that patients' strategies to deal
      with the situation at the ED are passive or active. The passive strategy is being
      patient and the active strategies varied in terms of having hidden tactics, using
      visible tactics and using families as support. CONCLUSION: These findings
      increase the importance of gaining knowledge about these strategies so that the
      staff at the ED can support the patients so they do not have to use them.

PMID- 24750521
TI  - Access to medicines and distributive justice: breaching Doha's ethical threshold.
AB  - The global health crisis in non-communicable diseases (NCDs) reveals a deep
      global health inequity that lies at the heart of global justice concerns.
      Mirroring the HIV/AIDS epidemic, NCDs bring into stark relief once more the human
      consequences of trade policies that reinforce global inequities in treatment
      access. Recognising distributive justice issues in access to medicines for their
      populations, World Trade Organisation (WTO) members confirmed the primacy of
      access to medicines for all in trade and public health in the landmark Doha
      Declaration on the TRIPS Agreement and Public Health of 2001. 

PMID- 24750522
TI  - Relevance of hepatitis B surface antigen levels in patients with chronic
      hepatitis B during 5 year of tenofovir treatment.
AB  - The role of quantitative hepatitis B surface antigen (HBsAg) levels in patients
      receiving highly potent oral antiviral therapy is controversial, and here, we
      determined the HBsAg response in 121 chronic hepatitis B patients treated with
      tenofovir 300 mg daily. During tenofovir treatment, HBsAg decline of >= 1.0 log
      from baseline was seen in 16.1%, 16.3%, 18.4%, 34.6%, 36.4% and 11.8%, 15.2%,
      14.8%, 28.6%, 20% at years 1, 2, 3, 4, 5 for HBeAg-positive and HBeAg-negative
      patients, respectively. Early decline in HBsAg levels at week 4 was predictive of
      subsequent significant HBsAg level decline. HBeAg seroconversion occurred in
      29.9% of HBeAg-positive patients. On multinomial logistic regression, HBsAg level
      decline from baseline at week 4 and week 12 or any time subsequently did not
      correlate with HBeAg seroconversion and HBV DNA level decline from baseline at
      week 4 and week 12 (OR = 3.704; 95% CI = 1.511-9.076; P = 0.006 and OR = 1.732;
      95% CI = 1.032-2.867; P = 0.037, respectively) was significantly predictive of
      seroconversion. A small proportion of chronic HBV-infected patients treated with
      tenofovir exhibit a significant (>= 1.0 log) decline in HBsAg levels. Early
      decline in HBsAg levels at week 4 was predictive of subsequent and significant
      HBsAg level decline. The HBsAg decline did not correlate with HBeAg
      seroconversion in HBeAg-positive patients. Reduction in HBV DNA levels at week 4
      and 12 correlated with seroconversion.

PMID- 24750523
TI  - Paging Dr Cohen, Paging Dr Cohen... An effect size interpretation is required
      STAT!: visualising effect size and an interview with Kristoffer Magnusson.

PMID- 24750524
TI  - Evidence-based screening to prevent and control cardiovascular disease worldwide.

PMID- 24750525
TI  - Creating and developing a non-profit community-outreach healthcare clinic in the
      developing world: lessons learnt in South Africa.
AB  - Chesed Children's Clinic is a non-profit, non-governmental, volunteer-run primary
      care paediatric-outreach clinic servicing the severely under-resourced informal
      settlement of Mzamomhle within South Africa's impoverished Eastern Cape Province.
      Founded in May 2011 by a group of junior medical professionals and volunteers,
      the clinic has been successfully operating a weekend clinic on alternate Sundays
      since September 2011. This paper discusses 10 points of essential consideration
      for individuals and organisations intent on pursuing similar projects. 

PMID- 24750526
TI  - Contemporary issues with pharmacotherapy for lower urinary tract symptoms.
AB  - Two articles appeared in the November 2012 edition of the journal evaluating
      aspects relating to the use of two important pharmacotherapeutic classes for
      lower urinary tract symptoms (LUTS) in real life clinical practice. LUTS is a non
      specific term that encompasses urine storage, voiding and postmicturition
      symptoms. LUTS is a common bothersome problem affecting both men and women with a
      comparable prevalence in age-matched patients of both sexes that increases with
      ageing.

PMID- 24750527
TI  - Endocarditis caused by Streptococcus infantarius subsp. infantarius: a report of
      two cases.

PMID- 24750528
TI  - Do randomised studies of traditional Asian therapies generate different results
      than non-randomised trials?

PMID- 24750529
TI  - The importance of lifestyle-based efforts in reducing mortality in overweight and
      obese individuals with type-2 diabetes.

PMID- 24750530
TI  - Depression, anxiety and reduced quality of life in predialysis: differences
      across the CKD stages?

PMID- 24750531
TI  - Reply to Chuang Li and colleagues' letter 'Depression, anxiety and reduced
      quality of life in predialysis: differences across the CKD stages?'.

PMID- 24750532
TI  - Barriers to care and treatment for patients with chronic viral hepatitis in
      Europe: a systematic review.
AB  - BACKGROUND & AIMS: Despite the availability of effective therapies for hepatitis
      B (HBV) and C virus (HCV), only a minority of these patients receive treatment.
      We systematically reviewed published data on barriers to management for chronic
      HBV/HCV patients in Europe. METHODS: Literature search to identify studies
      including adult patients with chronic HBV/HCV infection from European countries
      and data on barriers to treatment. RESULTS: Twenty-five studies including 6253
      chronic HBV and 19,014 HCV patients were identified, of which only two were from
      Eastern Europe. The mean rate of no treatment in HBV patients was 42% being
      higher in North-Western European countries than Italy (56% vs. 39%, P < 0.001).
      Immigrants represented the most common barrier to HBV treatment. The mean rate of
      no treatment in HCV RNA-positive patients was 57%, being highest in Romania
      (89%), intermediate in France (79%) and lower though still high in other European
      countries (52%, P < 0.001). The predominant barriers to HCV treatment were lack
      of financial resources in Romania and direct/indirect limitations of interferon
      alfa and/or parenteral drug and alcohol abuse in other countries. The mean rate
      of no treatment was highest in HCV RNA-positive parenteral drug users (72%) and
      intermediate in those with HCV-HIV co-infection (64%). CONCLUSIONS: A substantial
      proportion of diagnosed chronic HBV and the majority of diagnosed HCV patients
      remain untreated. The rates and most importantly the reasons of barriers to
      treatment in chronic HBV/HCV patients vary widely among European countries
      supporting the need for country-specific national strategies, resource allocation
      and implementation of global management policies.

PMID- 24750533
TI  - U wave variability in the surface ECG.
AB  - A 72-year-old man with heart failure, left ventricular dysfunction (ejection
      fraction 20%), prior ischemic stroke, COPD, and exacerbation of chronic renal
      failure was admitted in our unit. Serum potassium was 6.1 mmol/L, calcium
      concentration was at the lower normal range 2.15 mmol/L, and NT-pro-BNP was
      28,900 pg/mL. The surface 12-lead electrocardiogram (ECG) showed sinus rhythm at
      60 bpm, PR interval 160 ms, QRS duration 115 ms, QT interval 460 ms, and left
      ventricular hypertrophy criteria. Negative T waves in leads I, II, aVL, and V4 
      V6 were also seen. In leads V4 -V6 , negative U waves were observed in
      concordance with negative T waves. In all precordial leads, beat-to-beat U-wave
      polarity variability was observed as a polarity variation from negative to
      positive with associated and stable negative T waves, in a beat-to-beat alternate
      morphology.

PMID- 24750534
TI  - Community care for the Elderly: Needs and Service Use Study (CENSUS): Who
      receives home care packages and what are the outcomes?
AB  - AIM: Investigate factors associated with waiting times for home care packages and
      outcomes for care recipients and carers. METHOD: Analyses of data collected every
      four months for 12 months from 55 community-dwelling older adults eligible for
      government-subsidised packaged care and their carers. RESULTS: Thirty of fifty
      five participants were offered a package; they waited from one to 237 days.
      Baseline quality of life was higher for those offered a package than those not.
      Baseline care needs and unmet needs, neuropsychiatric symptoms, and cognitive
      decline did not predict offers. Package receipt compared to non-package receipt
      was associated with decreased carer burden over time but did not affect levels of
      unmet care needs, care needs or quality of life. CONCLUSIONS: Being offered a
      home care package was not based on waiting time or unmet care needs. Reforms
      should include a transparent system of wait listing and prioritisation.

PMID- 24750535
TI  - Mind the PVCs.

PMID- 24750536
TI  - Exploiting extension bias in polymerase chain reaction to improve primer
      specificity in ensembles of nearly identical DNA templates.
AB  - We describe a semi-empirical framework that combines thermodynamic models of
      primer hybridization with experimentally determined elongation biases introduced
      by 3'-end mismatches for improving polymerase chain reaction (PCR)-based sequence
      discrimination. The framework enables rational and automatic design of primers
      for optimal targeting of one or more sequences in ensembles of nearly identical
      DNA templates. In situations where optimal targeting is not feasible, the
      framework accurately predicts non-target sequences that are difficult to
      distinguish with PCR alone. Based on the synergistic effects of disparate sources
      of PCR bias, we used our framework to robustly distinguish between two alleles
      that differ by a single base pair. To demonstrate the applicability to
      environmental microbiology, we designed primers specific to all recognized
      archaeal and bacterial genera in the Ribosomal Database Project, and have made
      these primers available online. We applied these primers experimentally to obtain
      genus-specific amplification of 16S rRNA genes representing minor constituents of
      an environmental DNA sample. Our results demonstrate that inherent PCR biases can
      be reliably employed in an automatic fashion to maximize sequence discrimination
      and accurately identify potential cross-amplifications. We have made our
      framework accessible online as a programme for designing primers targeting one
      group of sequences in a set with many other sequences
      (http://DECIPHER.cee.wisc.edu). 

PMID- 24750537
TI  - Ageing across the Tasman Sea: the demographics and health of older adults in
      Australia and New Zealand.
AB  - OBJECTIVE: The demographic and health aspects of ageing populations in Australia
      and New Zealand (NZ) are described. These data are relevant to compare impacts of
      policy and context in each country. METHODS: Secondary analysis of international
      (Organization for Economic Co-operation and Development, United Nations and World
      Health Organization) and domestic population and health data. RESULTS: Both
      countries will experience a greater than 80% increase in the population aged 60
      plus years between 2013 and 2050. The increase in the 80-plus population will be
      200% or higher, resulting in 2.8 million Australians and more than 510,000 New
      Zealanders in this age group by 2050. The speed of ageing in both countries is
      higher than the average rate of increase in developed countries. Average life
      expectancy at birth and age 60 is higher in Australia than NZ, with the
      differences increasing slightly by 2050, and gaps between men and women
      consistently smaller in NZ than in Australia. However, a higher proportion of
      older Australians report living with a disability (53%) than older New Zealanders
      (45%). CONCLUSIONS: Australia and NZ are well aged in the context of a youthful
      Oceania region, with more similarities than differences between the countries.
      IMPLICATIONS: Both countries need to continue to monitor health trends, unravel
      the major population attributable risks, and identify preventative and other
      interventions that can stimulate and support declines in disability in older
      populations in the future, particularly for non-indigenous older persons.

PMID- 24750538
TI  - The regulation of aromatase and androgen receptor expression during gonad
      development in male and female European eel.
AB  - This research investigated the regulation of aromatase and androgen receptor gene
      expression in the brain-pituitary-gonad (BPG) axis of male and female European
      eels (Anguilla anguilla) during induced sexual maturation. Complete A. anguilla
      aromatase (aa-cyp19a1) and partial androgen receptor alpha and beta (aa-ara and
      aa-arb) sequences were isolated, and qPCR assays were validated and used for
      quantification of transcript levels for these three genes. Expression levels of
      the genes varied with sex, tissue and stage of maturation. aa-arb was expressed
      at higher levels than aa-ara in the pituitary and gonad in both sexes, suggesting
      aa-arb is the physiologically most important androgen receptor in these tissues.
      In the female brain, a decrease in aa-ara and an increase in aa-cyp19a1 were
      observed at the vitellogenic stage. In contrast, a progressive increase in all
      three genes was observed in the pituitary and ovaries throughout gonadal
      development, with aa-arb and aa-cyp19a1 reaching significantly higher levels at
      the vitellogenic stage. In the male pituitary, a decrease in aa-arb and an
      increase in aa-cyp19a1 were observed at the beginning of spermatogenesis, and
      thereafter remained low and high, respectively. In the testis, the transcript
      levels of androgen receptors and aa-cyp19a1 were higher during the early stages
      of spermatogenesis and decreased thereafter. These sex-dependent differences in
      the regulation of the expression of aa-ara, aa-arb and cyp19a1 are discussed in
      relation to the role of androgens and their potential aromatization in the
      European eel during gonadal maturation. 

PMID- 24750539
TI  - Expression of Niban in renal interstitial fibrosis.
AB  - AIM: Apoptosis is one of the most important mechanisms underlying renal
      interstitial fibrosis. We identified the role of protein Niban in apoptosis of
      tumour cells. The purpose of this study was to assess the expression of Niban in
      renal interstitial fibrosis of humans and rats. METHODS: Immunohistochemistry was
      used to detect Niban in patients with obstructive nephropathy. Proteomics and
      gene array analysis were performed to screen different molecules involved in the
      pathophysiology of unilateral-ureteral obstruction rats. We confirmed Niban using
      immunohistochemistry and Western blot in renal cortex of UUO rats and HK-2 cells.
      TUNEL assay and flow cytometry revealed apoptosis of renal tubular cells. siRNA
      and overexpression plasmid were transfected specifically to study the possible
      function of Niban. RESULTS: Niban was decreased apparently in renal tubular cells
      of patients with obstructive nephropathy, compared with controls. Niban decreased
      in renal cortex of UUO rats and transforming growth factor-beta1 (TGF-beta1)
      stimulated HK-2 cells. siRNA of Niban increased apoptosis of HK-2 cells. TGF
      beta1 also increased apoptosis of HK-2 cells. Overexpression of Niban failed to
      diminish apoptosis of HK-2 cells induced by TGF-beta1. CONCLUSIONS: Niban
      decreased in renal tubular cells of patients of obstructive nephropathy, UUO rats
      and TGF-beta1 stimulated HK-2 cells. Suppressing Niban increases apoptosis in HK
      2 cells. Niban may be associated with apoptosis of HK-2 cells.

PMID- 24750540
TI  - Surgical restoration of left ventricular diastolic function: possible treatment
      for noncompaction cardiomyopathy.
AB  - Noncompaction of the left ventricle is a rare congenital cardiomyopathy
      characterized by prematurely arrested compaction of the endocardial and
      myocardial fibers resulting in impaired systolic and diastolic ventricular
      function. Nontransplant surgical treatment is lacking and limited to correction
      of accompanied valve problems or arrhythmias. We present a technique for surgical
      restoration of ventricular diastolic function in a patient with noncompaction of
      the left ventricle.

PMID- 24750542
TI  - Asserting the primacy of health over patent rights: a comparative study of the
      processes that led to the use of compulsory licensing in Thailand and Brazil.
AB  - Since the 1970s, the United States has adopted a trade policy agenda that has
      forced countries to trade away flexible patent provisions for access to US
      markets. While pharmaceutical companies have argued that the recognition of
      patent rights is essential for recovering investments in research and development
      of pharmaceuticals and incentivizing future innovation, the lack of competition
      has had damaging consequences for public health, as companies tend to set the
      prices of treatments beyond the reach of consumers and government programs.
      Thailand and Brazil are bound by law to provide universal access to anti
      retroviral treatment (ART) to People Living with HIV/AIDS (PLWHA). This has been
      made possible in part due to the universal health care systems in each country
      and the countries' local technical and industrial capacities that provide the
      government with affordable generic medicines. The introduction of stronger
      intellectual property protection laws however, has limited possibilities for
      procuring generic medicines and inflated the cost of treatment. Between 2006
      2008, Thailand and Brazil used compulsory licensing to authorize generic
      competition against the consent of the pharmaceutical companies in order to
      guarantee the right to health and ensure the viability of government health
      budgets. This paper will demonstrate how the interaction between individual /
      collective action and structural and institutional elements in Thailand and
      Brazil produced propitious conditions for each country to assert the primacy of
      health over patent rights. 

PMID- 24750541
TI  - Human hypertrophic and keloid scar models: principles, limitations and future
      challenges from a tissue engineering perspective.
AB  - Most cutaneous wounds heal with scar formation. Ideally, an inconspicuous
      normotrophic scar is formed, but an abnormal scar (hypertrophic scar or keloid)
      can also develop. A major challenge to scientists and physicians is to prevent
      adverse scar formation after severe trauma (e.g. burn injury) and understand why
      some individuals will form adverse scars even after relatively minor injury.
      Currently, many different models exist to study scar formation, ranging from
      simple monolayer cell culture to 3D tissue-engineered models even to humanized
      mouse models. Currently, these high-/medium-throughput test models avoid the main
      questions referring to why an adverse scar forms instead of a normotrophic scar
      and what causes a hypertrophic scar to form rather than a keloid scar and also,
      how is the genetic predisposition of the individual and the immune system
      involved. This information is essential if we are to identify new drug targets
      and develop optimal strategies in the future to prevent adverse scar formation.
      This viewpoint review summarizes the progress on in vitro and animal scar models,
      stresses the limitations in the current models and identifies the future
      challenges if scar-free healing is to be achieved in the future.

PMID- 24750543
TI  - Soil-transmitted helminths in southern highland Rwanda: associated factors and
      effectiveness of school-based preventive chemotherapy.
AB  - OBJECTIVES: Preventive chemotherapy of schoolchildren against soil-transmitted
      helminths (STHs) is widely implemented in Rwanda. However, data on its actual
      efficacy are lacking. We assessed prevalence, associated factors and
      manifestation of STH infection among schoolchildren in southern highland Rwanda
      as well as cure and reinfection rates. METHODS: Six hundred and twenty-two
      children (rural, 301; urban, 321) were included preceding the administration of a
      single dose of 500 mg mebendazole. Before treatment, and after 2 and 15 weeks,
      STH infection was determined by Kato-Katz smears and by PCR assays for Ascaris
      lumbricoides. Clinical and anthropometric data, socio-economic status and factors
      potentially associated with STH infection were assessed. RESULTS: Soil
      transmitted helminth (STH) infection was present in 38% of rural and in 13% of
      urban schoolchildren. Ascaris lumbricoides accounted for 96% of infections. Of
      these, one-third was detected by PCR exclusively. Factors associated with STH
      infection differed greatly between rural and urban children. Likewise, STH
      infection was associated with stunting and anaemia only among urban children. The
      cure rate after 2 weeks was 92%. Among eight non-cleared A. lumbricoides
      infections, seven were submicroscopic. Reinfection within 3 months occurred in
      7%, but the rate was higher among rural children, and with initially present
      infection, particularly at comparatively high intensity. CONCLUSIONS: The rural
      urban difference in factors associated with STH infection and in reinfection
      rates highlights the need for targeted interventions to reduce transmission. PCR
      assays may help in detecting low-level infections persisting after treatment. In
      southern Rwanda, mebendazole is highly effective against the STH infections
      predominated by A. lumbricoides.

PMID- 24750544
TI  - Adherence therapy improves medication adherence and quality of life in people
      with Parkinson's disease: a randomised controlled trial.
AB  - BACKGROUND: Many factors are associated with medication non-adherence in
      Parkinson's disease (PD), including complex treatment regimens, mood disorders
      and impaired cognition. However, interventions to improve adherence which
      acknowledge such factors are lacking. A phase II randomised controlled trial was
      conducted investigating whether Adherence Therapy (AT) improves medication
      adherence and quality of life (QoL) compared with routine care (RC) in PD.
      METHODS: Eligible PD patients and their spouse/carers were randomised to
      intervention (RC plus AT) or control (RC alone). Primary outcomes were change in
      adherence (Morisky Medication Adherence Scale) and QoL (Parkinson's Disease
      Questionnaire-39) from baseline to week-12 follow up. Secondary outcomes were MDS
      UPDRS (part I, II, IV), Beliefs about Medication Questionnaire (BMQ), EuroQol (EQ
      5D) and the Caregiving Distress Scale. Blinded data were analysed using logistic
      and linear regression models based on the intention-to-treat principle. RESULTS:
      Seventy-six patients and 46 spouse/carers completed the study (intervention: n =
      38 patients, n = 24 spouse/carers). At week-12 AT significantly improved
      adherence compared with RC (OR 8.2; 95% CI: 2.8, 24.3). Numbers needed to treat
      (NNT) were 2.2 (CI: 1.6, 3.9). Compared with RC, AT significantly improved PDQ-39
      (-9.0 CI: -12.2, -5.8), BMQ general harm (-1.0 CI: -1.9, -0.2) and MDS-UPDRS part
      II (-4.8 CI: -8.1, -1.4). No significant interaction was observed between the
      presence of a spouse/carer and the effect of AT. CONCLUSION: Adherence Therapy
      improved self-reported adherence and QoL in a PD sample. The small NNT suggests
      AT may be cost-effective. A larger pragmatic trial to test the efficacy and cost
      effectiveness of AT by multiple therapists is required.

PMID- 24750545
TI  - Interferon-lambda4 genetic polymorphism is associated with the therapy response
      for hepatitis C virus recurrence after a living donor liver transplant.
AB  - The standard therapy against hepatitis C virus (HCV) recurrence postliver
      transplantation includes interferon (IFN)alpha and ribavirin. IFNL4 ss469415590
      polymorphism has been reported as a novel predictor of the response to IFN
      therapy for chronic HCV infection. We examined the impact of IFNL4 polymorphism
      on the responsiveness to IFN therapy after liver transplantation. Tissue
      specimens were collected from 80 HCV-infected recipients and 78 liver donors, and
      their IFNL4 ss469415590 genotype, hepatic IFNL4 and interferon-stimulated genes'
      mRNA expression levels were examined. The association of the polymorphism and
      expression levels in terms of the IFN therapy response to HCV recurrence was
      analysed. Most individuals who had rs8099917 risk alleles also had ss469415590
      risk alleles (R(2) = 0.9). Sustained virological response (SVR) rates were higher
      in both liver graft recipients and transplants with ss469415590 TT/TT alleles
      than in those with the risk DeltaG allele (P = 0.003 and P = 0.005,
      respectively). In recipients with ss469415590 TT/TT, IFNL4 TT mRNA levels showed
      no significant differences between livers of patients who responded to therapy
      and those who did not (P = 0.4). In recipients with the risk DeltaG allele, IFNL4
      DeltaG mRNA expression levels were significantly lower in SVR patients than in
      non-SVR patients (P = 0.02). Hepatic interferon stimulable genes and IFNL4 mRNA
      expression were correlated. Our findings suggest that analysing the ss469415590
      genotype and IFNL4 DeltaG expression provides a novel prediction strategy for the
      possible response to IFN therapy after liver transplantation.

PMID- 24750546
TI  - Does improvement in epidurography following percutaneous epidural neuroplasty
      correspond to patient outcome?
AB  - OBJECTIVE: The positive effects of percutaneous epidural neuroplasty (PEN) likely
      result from elimination of fibrous tissue. However, a direct link between
      epidural adhesions and pain symptoms is debatable. We tested the hypothesis that
      epidurographic improvements correspond to improved patient outcome. METHODS: In
      this prospective study, patients with a filling defect on initial epidurography
      underwent PEN. Two weeks later, contrast agent distribution around the target
      area was assessed with repeat epidurography. A successful treatment was defined
      as over a 50% reduction in visual analog scale (VAS) score 2 weeks postprocedure.
      The demographic data, history of lumbar spine operation, target nerve, diagnosis,
      VAS scores, degree of epidurographic improvement, and patient satisfaction were
      compared between the successful treatment group (Group I) and unsuccessful
      treatment group (Group II). RESULTS: Seventy-nine patients were included.
      Epidurographic findings improved in 67.1% of patients 2 weeks after the
      procedure. Following PEN, the mean VAS scores of all patients were significantly
      decreased at 2 weeks (4.12 +/- 2.34), 1 month (3.56 +/- 2.30), 3 months (3.84 +/-
      2.45), and 6 months (4.13 +/- 2.71) compared with the initial scores (7.82 +/-
      1.78). In the comparison between Groups I and II, the rate of epidurographic
      improvement in Group I was higher than in Group II (P = 0.022). Satisfaction in
      patients that had epidurographic improvement (median satisfaction: 4) was higher
      than in patients that did not have epidurographic improvement (median
      satisfaction: 3; P = 0.003). CONCLUSION: The epidurographic changes following PEN
      correlate with patient-assessed pain relief and satisfaction.

PMID- 24750547
TI  - Immunohistochemical localization of fibroblast growth factor-2 in the sheep ovary
      and its effects on pre-antral follicle apoptosis and development in vitro.
AB  - Studies with sheep are important to improve our knowledge about the factors that
      control folliculogenesis in mammals and to explore possible physiological
      differences among species. The aims of this study were to characterize FGF-2
      protein expression in ovine ovaries and to verify the effect of FGF-2 on the
      morphology, apoptosis and growth of ovine pre-antral follicles cultured in vitro.
      After collection, one fragment of ovarian tissue was fixed for histological
      analysis and TUNEL analysis (fresh control). The remaining fragments were
      cultured for 7 days in control medium (alpha-MEM(+) ) alone or supplemented with
      FGF-2 at different concentrations (1, 10, 50, 100 or 200 ng/ml). After culturing,
      ovarian tissue was destined to histology and TUNEL analysis, and oocyte and
      follicle diameters were measured. The immunostaining for FGF-2 was observed in
      oocytes from primordial, primary and secondary follicles, as well as in granulosa
      cells of secondary and antral follicles. The percentage of normal follicles was
      similar among control medium, 1 and 10 ng/ml FGF-2, and significantly higher than
      those observed in 50, 100 or 200 ng/ml FGF-2. A significant increase in follicle
      diameter was observed when tissues were cultured in 10, 50, 100 or 200 ng/ml FGF
      2 compared with the fresh control and the other treatments. Similar results were
      observed for oocyte diameter in tissues cultured with 50, 100 or 200 ng/ml FGF-2
      (p < 0.05). However, the percentage of apoptotic cells only decreased (p < 0.05)
      in ovarian tissues cultured in 1 or 10 ng/ml FGF-2 compared with the control
      medium and other FGF-2 treatments. In conclusion, this study demonstrated the
      presence of FGF-2 in ovine ovaries. Furthermore, 10 ng/ml FGF-2 inhibits
      apoptosis and promotes ovine follicle growth. As the sheep ovary is more similar
      to that of humans, the culture system demonstrated in this work seems to be an
      appropriate tool for studies towards human folliculogenesis. 

PMID- 24750549
TI  - The importance of klotho in phosphate metabolism and kidney disease.
AB  - The discovery of fibroblast growth factor-23 (FGF23) and its co-receptor alpha
      klotho has broadened our understanding of mineral metabolism and led to a renewed
      research focus on phosphate homeostatic pathways in kidney disease. Expanding
      knowledge of these mechanisms, both in normal physiology and in pathology,
      identifies targets for potential interventions designed to reduce the
      complications of renal disease, particularly the cardiovascular sequelae. FGF23
      has emerged as a major alpha-klotho-dependent endocrine regulator of mineral
      metabolism, functioning to activate vitamin D and as a phosphatonin. However,
      increasingly there is an appreciation that klotho may act independently as a
      phosphate regulator, as well as having significant activity in other key
      biological processes. This review outlines our current understanding of klotho,
      and its potential contribution to kidney disease and cardiovascular health. 

PMID- 24750548
TI  - Parental reflective functioning: analysis and promotion of the concept for
      paediatric nursing.
AB  - AIMS AND OBJECTIVES: To identify the definitional elements of parental reflective
      functioning and develop a framework for nurses to apply this concept in their
      clinical work with families. BACKGROUND: In recent years, researchers have
      concluded that parental reflective functioning is a key mechanism in the
      development of child attachment security leading to lifelong mental and physical
      health benefits. Despite its clinical relevance, little has been published in the
      nursing literature on this concept. DESIGN: Concept analysis. METHODS: The Walker
      and Avant (2011, Strategies for theory construction in nursing. Prentice Hall,
      Upper Saddle River, NJ) method of concept analysis and the Whittemore and Knafl
      (Journal of Advanced Nursing, 52, 2005, 546) method of integrative review were
      used. A search of the literature published from 1989-2013 was conducted using
      edited texts and online databases - Scopus, CINAHL, PubMed and PsychInfo. Among
      the 85 sources, 31 empirical studies, 17 book chapters, 32 review papers and five
      case studies were identified concerning parental reflective functioning. RESULTS:
      The concept of reflective functioning, defined as the capacity to envision the
      mental states of self and other, was first described in 1989 by Fonagy. Slade
      (Attachment and Human Development, 7, 2005, 269) expanded the concept
      specifically for parents (i.e. parental reflective functioning). Results of this
      concept analysis describe seven defining attributes and five antecedent
      conditions. Consequences of parental reflective functioning are related to a
      child's attachment early in life and behaviour later in life. A model case is
      provided to contextualise the concept. To date, there are three measures for
      parental reflective functioning. CONCLUSIONS: While parental reflective
      functioning has been predominately featured in psychology and parenting
      interventions, the potential consequences of secure attachment and longer-term
      children's behavioural outcomes suggest that the concept has global implications
      for paediatric nurses and primary healthcare clinicians. RELEVANCE TO CLINICAL
      PRACTICE: Parental reflective functioning offers exciting and promising
      opportunities for paediatric health and new approaches for those who provide
      paediatric health care.

PMID- 24750550
TI  - The changing pattern of measles, mumps and rubella vaccine uptake in egg-allergic
      children.

PMID- 24750551
TI  - Ethical Implications of Case-Based Payment in China: A Systematic Analysis.
AB  - How health care providers are paid affects how medicine is practiced. It is thus
      important to assess provider payment models not only from the economic
      perspective but also from the ethical perspective. China recently started to
      reform the provider payment model in the health care system from fee-for-service
      to case-based payment. This paper aims to examine this transition from an ethical
      perspective. We collected empirical studies on the impact of case-based payment
      in the Chinese health care system and applied a systematic ethical matrix that
      integrates clinical ethics and public health ethics to analyze the empirical
      findings. We identified eleven prominent ethical issues related to case-based
      payment. Some ethical problems of case-based payment in China are comparable to
      ethical problems of managed care and diagnosis related groups in high-income
      countries. However, in this paper we discuss in greater detail four specific
      ethical issues in the Chinese context: professionalism, the patient-physician
      relationship, access to care and patient autonomy. Based on the analysis, we
      cautiously infer that case-based payment is currently more ethically acceptable
      than fee-for-service in the context of China, mainly because it seems to lower
      financial barriers to access care. Nonetheless, it will be difficult to justify
      the implementation of case-based payment if no additional measures are taken to
      monitor and minimize its existing negative ethical implications. 

PMID- 24750552
TI  - VSL#3 probiotic treatment decreases bacterial translocation in rats with carbon
      tetrachloride-induced cirrhosis.
AB  - BACKGROUND & AIMS: Probiotics can prevent pathological bacterial translocation in
      cirrhosis by modulating intestinal microbiota and improving gut barrier and
      immune disturbances. To evaluate the effect of probiotic VSL#3 on bacterial
      translocation, intestinal microbiota, gut barrier and inflammatory response in
      rats with experimental cirrhosis. METHODS: Forty-six Sprague-Dawley rats with
      CCl4 -induced cirrhosis were randomized into two groups: VSL#3 group (n = 22)
      that received VSL#3 in drinking water, and water group (n = 24) that received
      water only. Treatment began at week 6 of cirrhosis induction and continued until
      laparotomy, performed 1 week after development of ascites or at week 20. A
      control group included 11 healthy rats. At this study end, we evaluated bacterial
      translocation, intestinal flora, intestinal barrier (ileal claudin-2 and 4, beta
      defensin-1, occludin and malondialdehyde as index of oxidative damage) and serum
      cytokines. RESULTS: Mortality during this study was similar in the VSL#3 group
      (10/22, 45%) and the water group (10/24, 42%) (P = 1). The incidence of bacterial
      translocation was 1/12 (8%) in the VSL#3 group, 7/14 (50%) in the water group (P
      = 0.03 vs. VSL#3 group) and 0/11 in the control group (P = 0.008 vs. water
      group). The concentration of ileal and caecal enterobacteria and enterococci was
      similar in the two groups of cirrhotic rats. The ileal occludin concentration was
      higher and ileal malondialdehyde and serum levels of TNF-alpha were lower in the
      VSL#3 group than in the water group (P < 0.05). CONCLUSIONS: VSL#3 decreases
      bacterial translocation, the pro-inflammatory state and ileal oxidative damage
      and increases ileal occludin expression in rats with experimental cirrhosis.

PMID- 24750553
TI  - Growth patterns of patients with 1p36 deletion syndrome.
AB  - 1p36 deletion syndrome is one of the most common subtelomeric deletion syndromes.
      Obesity is frequently observed in patients with this syndrome. Thus, it is
      important to evaluate the growth status of an individual patient. For this
      purpose, we accumulated recorded growth data from 44 patients with this syndrome
      and investigated the growth patterns of patients. Most of the patients showed
      weight parameters within normal limits, whereas a few of these patients showed
      intrauterine growth delay and microcephaly. The length of the patients after
      birth was under the 50th centile in most patients. Many patients showed poor
      weight gain after birth, and only two female patients were overweight. These
      findings indicate two different phenotypes of the 1p36 deletion syndrome. The
      overweight patients with 1p36 deletion started excessive weight gain after two
      years of life. This characteristic of the patients with 1p36 deletion syndrome is
      similar to Prader-Willi syndrome. 

PMID- 24750554
TI  - Enhanced heat shock protein 25 immunoreactivity in cranial nerve motoneurons and
      their related fiber tracts in rats prenatally-exposed to X-irradiation.
AB  - Alterations in histoarchitecture of the brainstem were examined
      immunohistochemically in 4-week-old rats with a single whole body X-irradiation
      at a dose of 0.5, 1.0, or 1.5 Gy on embryonic day (ED) 15 using anti-heat shock
      protein 25 (HSP25). HSP25 immunostaining was seen in the neuronal perikarya of
      cranial nerve motoneurons, that is, the motor and mesencephalic nuclei of the
      trigeminal nerve, facial nucleus, abducens nucleus and accessory facial nucleus
      in the pons, and the ambiguous nucleus, dorsal nucleus of vagus nerve and
      hypoglossus nucleus in the medulla oblongata of intact controls. In 0.5 to 1.5 Gy
      irradiated rats, HSP25 immunostaining in those neurons was more intense than in
      controls, while the most intense immunostaining was marked in 1.5 Gy-irradiated
      rats. HSP25 immunostaining was also apparent in the spinal tract of the
      trigeminal nerve and facial nerve tracts in 0.5 to 1.5 Gy-irradiated rats, but
      was faint in controls. Interestingly, HSP25 immunostaining was aberrantly
      enhanced in dendritic arbors in the magnocellular region of medial vestibular
      nucleus of 0.5-1.5 Gy-irradiated rats. Those arbors were identified as excitatory
      secondary vestibulo-ocular neurons by double immunofluorescence for HSP25 and SMI
      32. The results suggest an increase of HSP25 expression in cranial nerve
      motoneurons and their related fiber tracts from prenatal exposure to ionizing
      irradiation. This may be an adaptive response to chronic hypoxia due to malformed
      brain arteries caused by prenatal ionizing irradiation. 

PMID- 24750555
TI  - Encouraging general practitioners to complete the four-year-old Healthy Kids
      Check and provide healthy eating and physical activity messages.
AB  - OBJECTIVE: To describe the impact of a training and support intervention to
      encourage completion of the Healthy Kids Check (HKC) by general practitioners
      (GP) or practice nurses (PN) and provision of brief advice on diet and physical
      activity. METHODS: The intervention (June 2008 to July 2010) was delivered by
      Divisions of General Practice (DGP) in the Hunter New England (HNE) region of
      NSW, Australia, to members in 300 practices. Intervention impact was evaluated
      using Medicare data on the number of HKCs completed and a post-intervention
      telephone survey of randomly selected parents in HNE and rest of NSW. RESULTS:
      Training reached 31% of GPs (n~ 216/700) and 71% of PNs (n~320/450); 31% of four
      year-olds received a HKC in HNE compared to 15% in NSW; 27% of HNE parents
      (n=162) reported a GP or PN had provided advice during their child's vaccinations
      visit compared to 15% of parents (n=154) in NSW (p=0.002). There was no
      significant difference in proportion of children who had weight or height
      assessed (55.6% in HNE and 54.6% in NSW). CONCLUSIONS: Boosting HKC claims and
      healthy eating and physical activity messages in general practice is feasible.
      More intensive strategies are required if obesity prevention and management
      benefits are to be achieved. IMPLICATIONS: General practice is an important but
      under-utilised source of advice for parents and data for policy makers on
      childhood obesity in Australia.

PMID- 24750557
TI  - Contribution of infection and peripheral artery disease to severity of diabetic
      foot ulcers in Chinese patients.
AB  - AIM: The objective of the current ongoing study was to evaluate the
      characteristics of diabetic patients with newly diagnosed foot ulcer in Burn &
      Plastic Hospital of PLA General Hospital. METHODS: A total of 1002 consecutive
      patients presenting with a new foot ulcer between March 2007 and September 2013
      were enrolled. All enrolled patients were classified based on presence or absence
      of collateral infection, disabling comorbidities and peripheral arterial disease
      (PAD). RESULTS: Of patients, 70.05% had PAD, which occurred significantly more in
      elderly adults. Patients with PAD had higher incidence of infection (58.9% vs.
      41.5% in non-PAD group) and disabling comorbidities (79% in PAD and 61% in non
      PAD; p < 0.038). There was no significant difference observed in depth, size and
      duration of foot ulcers between the PAD and non-PAD group of enrolled diabetic
      patients. CONCLUSIONS: Diabetic foot ulcer is more prominent in patients with PAD
      that is further reflected by significantly more underlying cases of infection and
      disabling comorbidity.

PMID- 24750556
TI  - Distance to emergency obstetric services and early neonatal mortality in
      Ethiopia.
AB  - OBJECTIVES: To assess the effect of distance to emergency obstetric and newborn
      care (EmONC) services on early neonatal mortality in rural Ethiopia and examine
      whether proximity to services contributes to socio-economic inequalities in early
      neonatal mortality. METHODS: We linked data from the 2011 Ethiopian Demographic
      and Health Survey with facility data from the 2008 Ethiopian National EmONC Needs
      Assessment based on geographical coordinates collected in both surveys. Health
      facilities were classified based on the performance of nine EmONC signal
      functions (e.g. neonatal resuscitation, Caesarean section). We used multivariable
      logistic regression to assess the relationship between distance to services and
      early neonatal mortality. A decomposition approach was used to quantify the
      relative contributions of distance to EmONC services and other determinants to
      overall and socio-economic inequality in early neonatal mortality. RESULTS: In
      general, closer proximity to EmONC services and higher level of care were
      associated with lower early neonatal mortality. Living more than 80 km from the
      nearest comprehensive EmONC facility able to perform all nine signal functions
      compared to living within 10 km was associated with an increase of 14.4 early
      neonatal deaths per 1000 live births (95% CI: 0.1, 28.7). Closer proximity to a
      substandard EmONC facility compared with no facility was not associated with
      lower early neonatal mortality. Distance to EmONC services was an important
      determinant of early neonatal mortality, although it did not make a significant
      contribution to explaining socio-economic inequality. CONCLUSIONS: Our results
      suggest that recent initiatives by the Ethiopian government to improve
      geographical access to EmONC services have the potential to reduce early neonatal
      mortality but may not affect inequalities.

PMID- 24750558
TI  - Effectiveness and Tolerability of a Moderate Dose of Tapentadol Prolonged Release
      for Managing Severe, Chronic Low Back Pain with a Neuropathic Component: An Open
      label Continuation Arm of a Randomized Phase 3b Study.
AB  - OBJECTIVE: To evaluate the effectiveness and tolerability of tapentadol prolonged
      release (PR) for severe, chronic low back pain with a neuropathic component in a
      subpopulation that achieved adequate pain relief with tapentadol PR 300 mg/day in
      a randomized, double-blind, phase 3b study. METHODS: Patients with painDETECT
      "unclear" or "positive" ratings and pain intensity >= 6 (11-point NRS-3 [average
      3-day pain intensity]) were titrated to tapentadol PR 300 mg/day over 3 weeks. A
      subpopulation with pain intensity < 4 continued receiving tapentadol PR 300
      mg/day during an 8-week, open-label continuation arm. For the primary study
      population, patients with >= 1-point decrease from baseline and pain intensity >=
      4 were randomized to tapentadol PR 500 mg/day or tapentadol PR 300 mg/day plus
      pregabalin 300 mg/day during a concurrent 8-week, double-blind comparative
      period. RESULTS: From baseline to end of titration and to final evaluation,
      significant improvements were observed in pain intensity (mean [SD] changes from
      baseline to: end of titration; - 5.3 [1.78]; final evaluation; - 5.2 [2.39]; both
      P < 0.0001), neuropathic pain symptoms, and quality-of-life measures in the open
      label continuation arm, with greater improvements in this selected subpopulation
      than in either group in the primary study population. A favorable tolerability
      profile was observed, with incidences of all individual treatment-emergent
      adverse events <= 5.1% during the continuation period. CONCLUSIONS: A
      subpopulation of patients with low back pain with a neuropathic component
      responded very well to tapentadol PR 300 mg/day, with significant improvements in
      pain intensity, neuropathic pain-related symptoms, and quality of life. Further
      research is needed to identify factors associated with a very positive treatment
      response.

PMID- 24750559
TI  - The cost-effectiveness of contemporary home haemodialysis modalities compared
      with facility haemodialysis: a systematic review of full economic evaluations.
AB  - AIM: The financial burden of the increasing dialysis population challenges
      healthcare resources internationally. Home haemodialysis offers many benefits
      over conventional facility dialysis including superior clinical, patient-centred
      outcomes and reduced cost. This review updates a previous review, conducted a
      decade prior, incorporating contemporary home dialysis techniques of frequent and
      nocturnal dialysis. We sought comparative cost-effectiveness studies of home
      versus facility haemodialysis (HD) for people with end-stage kidney failure
      (ESKF). METHODS: We conducted a systematic review of literature from January 2000
      March 2014. Studies were included if they provided comparative information on the
      costs, health outcomes and cost-effectiveness ratios of home HD and facility HD.
      We searched medical and health economic databases using MeSH headings and text
      words for economic evaluation and haemodialysis. RESULTS: Six studies of economic
      evaluations that compared home to facility HD were identified. Two studies
      compared home nocturnal HD, one home nocturnal and daily home HD, and three
      compared contemporary home HD to facility HD. Overall these studies suggest that
      contemporary home HD modalities are less costly and more effective than facility
      HD. Home HD start-up costs tend to be higher in the short term, but these are
      offset by cost savings over the longer term. CONCLUSIONS: Contemporaneous
      dialysis modalities including nocturnal and daily home haemodialysis are cost
      effective or cost-saving compared with facility-based haemodialysis. This result
      is largely driven by lower staff costs, and better health outcomes for survival
      and quality of life. Expanding the proportion of haemodialysis patients managed
      at home is likely to produce cost savings.

PMID- 24750560
TI  - The mediating effect of psychological distress on functional dependence in stroke
      patients.
AB  - AIMS AND OBJECTIVES: To explore varied forms of psychological distress and to
      determine the mediating influence of psychological distress on functional
      outcomes in stroke patients. BACKGROUND: Previous studies attest to the influence
      of depression on poststroke functional recovery. While there is evidence for
      neuropathological deficits that occur after stroke to be associated with
      psychological distress, few studies have explored the effect of various types of
      psychological distress on functional recovery. DESIGN: A cross-sectional study
      was used. METHODS: Data were collected from 178 first-time stroke patients. Study
      variables included demographic and disease characteristics (stroke location and
      stroke syndrome classification), psychological distress (the Chinese language
      version of the Emotional and Social Dysfunction Questionnaire) and functional
      outcome (Barthel index). Regression and mediation models were used to evaluate
      the effect of psychological distress on functional outcome. RESULTS: Results
      revealed that stroke patients experience various forms of mild psychological
      distress, including anger, helplessness, emotional dyscontrol, indifference,
      inertia and euphoria, after stroke. Regression and mediation analyses further
      confirmed that various forms of psychological distress significantly mediated the
      effect of severe stroke syndromes on functional dependence. CONCLUSION: The
      various forms of psychological distress after stroke might play a mediating role
      in functional recovery and explain how stroke severity affects functional
      dependence. RELEVANCE TO CLINICAL PRACTICE: By understanding the nature of
      various forms of psychological distress, healthcare professionals should adopt
      appropriate assessment instruments and design effective interventions to help
      improve mental and physical function of stroke patients.

PMID- 24750561
TI  - Latest trends in the assessment and surgical management of snoring in England: a
      prospective questionnaire study.

PMID- 24750562
TI  - Bioethics in the Malay-Muslim Community in Malaysia: A Study on the Formulation
      of Fatwa on Genetically Modified Food by the National Fatwa Council.
AB  - The field of bioethics aims to ensure that modern scientific and technological
      advancements have been primarily developed for the benefits of humankind. This
      field is deeply rooted in the traditions of Western moral philosophy and socio
      political theory. With respect to the view that the practice of bioethics in
      certain community should incorporate religious and cultural elements, this paper
      attempts to expound bioethical tradition of the Malay-Muslim community in
      Malaysia, with shedding light on the mechanism used by the National Fatwa Council
      to evaluate whether an application of biological sciences is ethical or not. By
      using the application of the genetically modified food as a case study, this
      study has found that the council had reviewed the basic guidelines in the main
      references of shari'ah in order to make decision on the permissibility of the
      application. The fatwa is made after having consultation with the experts in
      science field. The council has taken all factors into consideration and given
      priority to the general aim of shari'ah which to serve the interests of mankind
      and to save them from harm. 

PMID- 24750563
TI  - Decreased granulomatous reaction by polyurethane-coated stent in the trachea.
AB  - BACKGROUND: Reducing granulomatous reaction for stent implantation is important
      for the treatment of tracheobronchomalacia because formation of granuloma leads
      to refractory complication causing further respiratory distress. The purpose of
      this study was to clarify granulomatous reaction of newly innovated coated stents
      compared to non-coated metal stents. METHODS: Materials and animal experiments
      were performed using the newly invented metallic stent (laser-cut stainless steel
      with a coating of polyurethane). In the materials experiment, the correlation
      between the holding force and deformity was tested by a compressor. In the animal
      examination, coated stents were orally implanted into the trachea in five
      rabbits, while non-coated stents were implanted in another five rabbits. After 3
      weeks' observation, the inner diameter was measured by 3-D computed tomography,
      and the number of granulation tissues was counted by bronchofiberscope.
      Histological investigation followed in both groups. RESULTS: In the materials
      experiment, new stents demonstrated a holding force similar to stainless steel
      stents. In the animal experiment, no difference was found in the inner diameter
      of the coated and non-coated stent groups (5.70 +/- 0.17 vs 5.60 +/- 0.27, P =
      0.07). However, the number of granulation tissues was higher in non-coated stents
      than in coated stents (1.60 +/- 0.55 vs 0.40 +/- 0.55, P < 0.01). Histological
      investigation showed direct attachment of metal to the tracheal wall around the
      non-coated stents where epithelial structure was destroyed, while tracheal
      epithelia were preserved in the group of coated stents. CONCLUSIONS: The new
      polyurethane-coated metallic stent maintains enough holding force, and reduces
      histobiological reaction to foreign bodies in this experiment.

PMID- 24750564
TI  - Degree of polymerization of 5,6-dihydroxyindole-derived eumelanin from chemical
      degradation study.
AB  - Eumelanin is a brown-black pigment comprising 5,6-dihydroxyindole (DHI) and its 2
      carboxy derivative (DHICA), but the detailed structure of eumelanin is unclear.
      Chemical degradation is a powerful tool for analyzing melanin. H2 O2 oxidation
      degradation of eumelanin affords pyrrole-2,3,5-tricarboxylic acid (PTCA) and
      pyrrole-2,3-dicarboxylic acid (PDCA). The ratio of PDCA to PTCA provides
      information about the eumelanin structure. In this article, we propose simple
      equations on the basis of previous experimental results on dimer yields for
      evaluating the yields of PTCA and PDCA from any DHI oligomers. Assuming the
      chemical disorder model of DHI-melanin, we solve an equation where a theoretical
      expression for the ratio of PDCA to PTCA is set to the corresponding experimental
      value to obtain a plausible Poisson distribution of DHI oligomers. The results
      demonstrate that the main contributors to DHI-melanin are tetramers and pentamers
      as shown by the mass spectrometry.

PMID- 24750565
TI  - Antibiotic prescribing practice for acute, uncomplicated respiratory tract
      infections in primary care settings in New Delhi, India.
AB  - OBJECTIVE: To obtain information on prescribing rates and choice of antibiotics
      for acute, uncomplicated respiratory tract infections (RTIs) in the community.
      METHODS: Antibiotic use in acute, uncomplicated RTIs consisting of common
      cold/sore throat/cough for not more than five days was surveyed in the community
      (December 2007-November 2008) using patient exit interviews at public and private
      facilities from four localities in New Delhi. Data were collected from 10 public
      sector facilities and 20 private clinics over one year. The percentage of acute,
      uncomplicated RTIs patients receiving antibiotics in general and using the
      Anatomical Therapeutic Chemical classification and the Defined Daily Dose
      (ATS/DDD) were analysed. RESULTS: At public and private facilities, 45%
      (746/1646) and 57% (259/457) of acute, uncomplicated RTI patients were prescribed
      at least one antibiotic, respectively. The main antibiotic class calculated as
      percentage of total antibiotics DDDs/1000 prescribed to acute, uncomplicated RTI
      patients at private clinics was cephalosporins, J01DA (39%), followed by
      fluoroquinolones, J01MA (24%), penicillins, J01C (19%) and macrolides, J01FA
      (15%). Newer members from each class were prescribed; older antibiotics such as
      co-trimoxazole or tetracyclines were rarely prescribed. At public facilities, the
      main class of antibiotic prescribed was penicillins (31%), followed by macrolides
      (25%), fluoroquinolones (20%) and cephalosporins (10%). CONCLUSIONS: Study
      clearly shows overuse and inappropriate choice of antibiotics for the treatment
      of acute, uncomplicated RTIs which are mainly due to virus and do not require
      antibiotic treatment. Results of the study warrant interventional strategies to
      promote rational use of antibiotics to decrease the overgrowing threat of
      antibiotic resistance.

PMID- 24750566
TI  - Occult hepatitis B virus infection predicts de novo hepatitis B infection in
      patients with alcoholic cirrhosis after liver transplantation.
AB  - BACKGROUND & AIMS: Occult hepatitis B virus infection (OBI) in patients
      undergoing liver transplantation (LT) is a suspected source of de novo hepatitis
      B virus (HBV) infection after LT. This study aimed to investigate the prevalence
      of OBI in liver transplant recipients with alcoholic cirrhosis and demonstrate
      the association between OBI and de novo HBV infection after LT in these patients.
      METHODS: Forty-three patients with alcoholic cirrhosis who were negative for
      HBsAg before LT were recruited in this retrospective study. DNA was extracted
      from paraffin-embedded native liver tissues and quantified for HBV DNA by real
      time PCR. Correlation between de novo HBV infection after LT (positive HBsAg
      and/or detectable HBV DNA in serum) and detection of intrahepatic HBV DNA before
      LT was analysed. RESULTS: Detectable HBV DNA in the explanted liver was found in
      41.9% (18/43) of the patients and was thus defined as OBI, which was correlated
      with the presence of serum hepatitis B core antibody (P = 0.008). De novo HBV
      infection occurred in 18.6% (8/43) of the recipients at a median of 10 months
      after LT. The rate of de novo HBV infection was 38.9% (7/18) in patients with
      OBI, compared with 4% (1/25) in patients without OBI (P = 0.004). Furthermore, de
      novo HBV infection was inversely correlated with the presence of hepatitis B
      surface antibody in recipients with OBI (P = 0.026). CONCLUSION: With a
      prevalence of 41.9% in liver transplant recipients with alcoholic cirrhosis, OBI
      in the native liver can predict de novo HBV infection after LT.

PMID- 24750567
TI  - Ultrasonography in pain practice: moving on.

PMID- 24750568
TI  - Local rhamnosoft, ceramides and L-isoleucine in atopic eczema: a randomized,
      placebo controlled trial.
AB  - BACKGROUND: A non-steroidal, anti-inflammatory moisturizing cream containing
      rhamnosoft, ceramides, and L-isoleucine (ILE) (pro-AMP cream) has been recently
      developed for the specific treatment of atopic eczema (AE) of the face. In this
      trial, we evaluated the clinical efficacy and tolerability of pro-AMP cream in
      the treatment of facial AE in children in comparison with an emollient cream.
      METHODS: In a randomized, prospective, assessor-blinded, parallel groups (2:1)
      controlled trial, 107 children (72 allocated to pro-AMP cream and 35 allocated to
      control group) with mild-to-moderate chronic AE of the face were enrolled.
      Treatments were applied twice daily for a 6-week period. Facial Eczema Severity
      Score (ESS) was evaluated at baseline, week 3, and week 6, by an assessor unaware
      of treatment allocation. Investigator's Global Assessment (IGA) score was
      assessed at week 3 and at week 6. Tolerability was evaluated at week 3 and at
      week 6 using a4-point score (from 0: low tolerability to 3: very good
      tolerability). RESULTS: At baseline ESS, mean (SD) was 6.1 (2.4) in the pro-AMP
      cream group and 5.3 (3) in the control group. In the pro-AMP group, in comparison
      with baseline, ESS was significantly reduced to 2.5 (-59%) after 3 wks and to 1.0
      (-84%) at week 6 (p = 0.0001). In the control group, ESS was reduced to 3 (-42%)
      at week 2 and to 2.6(-50%) at week 6. At week 6, ESS in pro-AMP cream was
      significantly lower than the control group (1.0 vs. 2.6; p = 0.001). Both
      products were well tolerated. CONCLUSION: Pro-AMP cream has shown to be effective
      in the treatment of mild-to moderate chronic lesion of AE of the face. Clinical
      efficacy was greater in comparison with an emollient cream. ( CLINICAL TRIAL
      REGISTRY: NTR4084).

PMID- 24750569
TI  - Food-derived peptides in a diagnostic context: the fewer the better?

PMID- 24750570
TI  - Anxiety and stress in mothers of food-allergic children.
AB  - BACKGROUND: Previous reports suggest that parents especially mothers of food
      allergic children may have increased anxiety. Studies with an appropriate control
      group have not been undertaken, and the determinants of such anxiety are not
      known. We compared measures of anxiety and stress in mothers of food-allergic
      children and atopic non-food-allergic children, with anxiety and stress in
      mothers of children with no chronic illness. METHODS: Cross-sectional study of
      mothers attending a hospital appointment for their 8- to 16-year-old child.
      Mothers of children with food allergy, asthma but no food allergy or no chronic
      illness completed questionnaires including State-Trait Anxiety Inventory,
      Perceived Stress Scale and measures of anxiety and psychologic adjustment in
      their child. RESULTS: Forty mothers of food-allergic children, 18 mothers of
      asthmatic children without food allergy and 38 mothers of children with no
      chronic illness (controls) were recruited. Mothers of food-allergic children
      showed increased state anxiety - median anxiety score 38.0 (IQR 30.0, 44.0) food
      allergy, 27.0 (22.0, 40.0) control p = 0.012; and increased stress - median
      stress score 18.5 (12.0, 22.0) food allergy, 14.0 (7.5, 19.5)control p = 0.035.
      No significant differences were seen between mothers in the asthmatic group and
      controls. In multivariate analysis, previous food anaphylaxis(p = 0.008) and
      poorly controlled asthma (p = 0.004) were associated with increased maternal
      anxiety. Child anxiety and adjustment did not differ between food-allergic and
      control groups. CONCLUSIONS: Mothers of food-allergic children have increased
      anxiety and stress compared with mothers of children with no chronic illness.
      Anaphylaxis and poorly controlled asthma are associated with maternal anxiety.

PMID- 24750572
TI  - Severe post-transplant lymphoproliferative disorder after living donor liver
      transplantation.
AB  - Post-transplant lymphoproliferative disorder (PTLD) is a well-known complication
      after transplantation. A living donor liver transplantation was performed on a 31
      year-old man for fulminant hepatitis. He again developed liver dysfunction after
      7 months. He was diagnosed as having acute cellular rejection and the steroid
      pulse therapy introduced resulted in little improvement. He gradually developed a
      high fever and right axillary lymphadenopathy appeared. Chest computed tomography
      (CT) was performed revealing small lung nodules and axillary lymphadenopathy.
      Because his serological status for Epstein-Barr virus was positive, PTLD was
      highly suspected and immunosuppression treatment was withdrawn with little
      improvement. One week later, he developed tachycardia. Chest CT was re-performed
      revealing an infiltration to the left cardiac chamber. For diagnosis, axillary
      lymph node biopsy was performed and during the procedure, he developed
      ventricular tachycardia (VT). Immunohistological staining revealed PTLD of T
      lymphocytes, and chemotherapy was introduced on the same day he developed VT.
      After two cycles of tetrahydropyranyl, adriamycin, cyclophosphamide, vincristine,
      prednisolone and etoposide treatment, he completely recovered. This is a first
      case report of severe PTLD with VT, and our case implies the feasibility of
      chemotherapy after the appearance of dissemination symptoms. 

PMID- 24750573
TI  - Patent Funded Access to Medicines.
AB  - Instead of impeding access to essential medicines in developing countries, the
      essay explores why and how patents can serve as a source of funding for the much
      needed access to medicine. Instead of a weakening of patents, prolonged
      protection periods are suggested in circumstances where there is widespread lack
      of access. The revenues from extended patents are seen as a source of funding for
      drug donations to the least developed countries. 

PMID- 24750571
TI  - Birthweight and the risk of atopic diseases: the ISAAC Phase III study.
AB  - BACKGROUND: The association between birthweight and asthma, eczema and
      rhinoconjunctivitisis conflicting. AIMS: To examine the association between
      birthweight and symptoms of asthma, eczema and rhinoconjunctivitis. METHODS:
      Parents or guardians of children aged 6-7 yr completed written questionnaires
      about symptoms of asthma, rhinoconjunctivitis and eczema, and several risk
      factors, including birthweight. RESULTS: There were 162,324 children from 60
      centres in 26 countries. Low birthweight(<2.5 kg) was associated with an
      increased risk of symptoms of asthma (current wheeze odds ratio = 1.20; 95%
      confidence interval = 1.12-1.30). Low birthweight was associated with a lower
      risk of eczema ever. Low birthweight was not associated with rhinoconjunctivitis.
      Large babies (birthweight >=4.5 kg) were not associated with any of these
      outcomes. CONCLUSIONS: This study has confirmed that low birthweight is a risk
      factor for symptoms of asthma, but not for rhinoconjunctivitis. The findings for
      eczema are equivocal.

PMID- 24750574
TI  - The Socioeconomic Impacts of Clinically Diagnosed Haemorrhagic Septicaemia on
      Smallholder Large Ruminant Farmers in Cambodia.
AB  - Haemorrhagic septicaemia (HS) is an acute fatal infectious disease of mainly
      cattle and buffalo and outbreaks occur commonly in Cambodia. Disease outbreak
      reports were examined to select five villages from three provinces for a
      retrospective investigation of HS epidemiology and socioeconomic impact on
      smallholders, with an aim of identifying potential benefits from improving
      disease prevention through biosecurity and vaccination. The Village Animal Health
      Worker (VAHW) or Chief in each village and 66 affected smallholders were
      surveyed. At the village level, 24% of all households were affected with an
      estimated mean village herd morbidity of 10.1% and mortality of 28.8%. Affected
      farmers reported HS disease morbidity and mortality at 42.7% and 63.6%
      respectively. Buffalo had a higher morbidity (OR = 2.3; P = 0.003) and mortality
      (OR = 6.9; P < 0.001) compared with cattle, and unvaccinated large ruminants a
      higher morbidity (OR = 2.9; P = 0.001). The financial impact varied depending on
      whether the animal survived, provision of treatment, draught replacement and lost
      secondary income. The mean cost per affected household was USD 952.50 based on
      ownership of five large ruminants. The impact per affected animal was USD 375.00,
      reducing the pre-disease value by 66.1%. A partial budget revealed an
      overwhelming incentive for farmers to practice biannual vaccination, with a net
      benefit of USD 951.58 per household based on an annual disease incidence rate of
      1. Sensitivity analysis showed that a net benefit of USD 32.42 remained based on
      an outbreak every 20 years. This study indicates HS can cause a catastrophic
      financial shock to smallholders and remains a critical constraint to improving
      large ruminant productivity and profitability. Addressing HS disease control
      requires a focus on improving smallholder farmer knowledge of biosecurity and
      vaccination and should be priority to stakeholders interested in addressing
      regional food insecurity and poverty reduction.

PMID- 24750575
TI  - Geographic segregation and evidence of density-dependent changes in sex ratios in
      an abundant colonial waterbird.
AB  - Demographic information, such as geographic segregation of sexes and sex ratio
      data, is needed to develop, model and evaluate conservation and management
      strategies for wildlife. A variety of physiological, behavioral and environmental
      factors can influence segregation of sexes and sex ratios, many of which
      originate with density-dependent processes. Departure from 50:50 sex ratios of
      double-crested cormorants (Phalacrocorax auritus) collected during control
      efforts in breeding and wintering areas across their eastern range of the USA
      were evaluated using using a Z-test as well as Stouffer's weighted Z-tests. In
      addition, a specifically-designed randomization test was used to evaluate density
      dependent effects on primary sex ratios in cormorants from egg collections and
      colony nest count data over a 21-year period. Cormorants collected from breeding
      colonies were strongly male-biased, whereas cormorants collected from feeding
      flocks were slightly biased toward females. Cormorants were partly segregated by
      sex on the wintering grounds, with significantly more males found in areas with
      intensive channel catfish aquaculture. The null hypothesis that females produced
      a balanced sex ratio independent of number of nesting cormorants was rejected:
      more male embryos were produced during rapid population growth, whereas at
      maximum nesting number more female embryos were produced. Once populations
      stabilized, the sex ratio was more equal. This examination of sex ratios
      indicates that different management methods and locations result in sex-biased
      culling of cormorants. Sex-biased culling in cormorants could make population
      reduction efforts more efficient and reduce overall take. We suggest further
      research to examine density-dependent effects on primary sex ratios documented
      here. 

PMID- 24750576
TI  - Oxide Wizard: an EELS application to characterize the white lines of transition
      metal edges.
AB  - Physicochemical properties of transition metal oxides are directly determined by
      the oxidation state of the metallic cations. To address the increasing need to
      accurately evaluate the oxidation states of transition metal oxide systems at the
      nanoscale, here we present "Oxide Wizard." This script for Digital Micrograph
      characterizes the energy-loss near-edge structure and the position of the
      transition metal edges in the electron energy-loss spectrum. These
      characteristics of the edges can be linked to the oxidation states of transition
      metals with high spatial resolution. The power of the script is demonstrated by
      mapping manganese oxidation states in Fe3O4/Mn3O4 core/shell nanoparticles with
      sub-nanometer resolution in real space. 

PMID- 24750578
TI  - The interpretation of very high frequency band of instantaneous pulse rate
      variability during paced respiration.
AB  - BACKGROUND: Pulse rate (PR) indicates heart beat rhythm and contains various
      intrinsic characteristics of peripheral regulation. Pulse rate variability (PRV)
      is a reliable method to assess autonomic nervous system function quantitatively
      as an effective alternative to heart rate variability. However, the frequency
      range of PRV is limited by the temporal resolution of PR based on heart rate and
      it is further restricted the exploration of optimal autoregulation frequency
      based on spectral analysis. METHODS: Recently, a new novel method, called
      instantaneous PRV (iPRV), was proposed. iPRV breaks the limitation of temporal
      resolution and extends the frequency band. Moreover, iPRV provides a new
      frequency band, called very high frequency band (VHF; 0.4-0.9 Hz). RESULTS: The
      results showed that the VHF indicated the influences of respiratory maneuvers
      (paced respiration at 6-cycle and 30-cycle) and the nonstationary condition (head
      up tilt; HUT). CONCLUSIONS: VHF is as a potential indication of autoregulation in
      higher frequency range and with peripheral regulation. It helps for the frequency
      exploration of cardiovascular autoregulation.

PMID- 24750579
TI  - Between Relativism and Imperialism: Navigating Moral Diversity in Cross-Cultural
      Bioethics.
AB  - The need for explicit theoretical reflection on cross-cultural bioethics
      continues to grow as the spread of communication technologies and increased human
      migration has made interactions between medical professionals and patients from
      different cultural backgrounds much more common. I claim that this need presents
      us with the following dilemma. On the one hand, we do not want to operate
      according to an imperialist ethical framework that denies and silences the
      legitimacy of cultural values other than our own. On the other hand, we do not
      want to backslide into a form of cultural relativism that is unable to critically
      appraise cultural practices that are harmful, unjust, or oppressive. I examine
      two prominent attempts - the principlism of Tom Beauchamp and James Childress and
      the Contractarianism of Robert Baker - to frame cross-cultural bioethics between
      these two extremes and argue that both approaches have significant flaws. The
      principlist approach fails to provide a non-question begging way to identify
      cross-cultural norms that does not already assume the universal legitimacy of
      moral principles dominant in North American society. Baker's contractarianism
      cannot grapple with the realities of political power imbalances that often
      characterize cross-cultural moral disputes. I suggest that a naturalized feminist
      framework, though not free of its own theoretical difficulties, provides the best
      alternative for approaching moral diversity respectfully and critically. 

PMID- 24750580
TI  - New variant of porcine epidemic diarrhea virus, United States, 2014.

PMID- 24750581
TI  - Anxiety and stress in mothers of food-allergic children.
AB  - BACKGROUND: Previous reports suggest that parents especially mothers of food
      allergic children may have increased anxiety. Studies with an appropriate control
      group have not been undertaken, and the determinants of such anxiety are not
      known. We compared measures of anxiety and stress in mothers of food-allergic
      children and atopic non-food-allergic children, with anxiety and stress in
      mothers of children with no chronic illness. METHODS: Cross-sectional study of
      mothers attending a hospital appointment for their 8- to 16-year-old child.
      Mothers of children with food allergy, asthma but no food allergy or no chronic
      illness completed questionnaires including State-Trait Anxiety Inventory,
      Perceived Stress Scale and measures of anxiety and psychologic adjustment in
      their child. RESULTS: Forty mothers of food-allergic children, 18 mothers of
      asthmatic children without food allergy and 38 mothers of children with no
      chronic illness (controls) were recruited. Mothers of food-allergic children
      showed increased state anxiety - median anxiety score 38.0 (IQR 30.0, 44.0) food
      allergy, 27.0 (22.0, 40.0) control p = 0.012; and increased stress - median
      stress score 18.5 (12.0, 22.0) food allergy, 14.0 (7.5, 19.5) control p = 0.035.
      No significant differences were seen between mothers in the asthmatic group and
      controls. In multivariate analysis, previous food anaphylaxis (p = 0.008) and
      poorly controlled asthma (p = 0.004) were associated with increased maternal
      anxiety. Child anxiety and adjustment did not differ between food-allergic and
      control groups. CONCLUSIONS: Mothers of food-allergic children have increased
      anxiety and stress compared with mothers of children with no chronic illness.
      Anaphylaxis and poorly controlled asthma are associated with maternal anxiety.

PMID- 24750582
TI  - Full-Genome Sequencing of Four Bluetongue Virus Serotype 11 Viruses.
AB  - Recently, a contamination incident was described in which the challenge inoculum
      used in a bluetongue virus serotype 8 (BTV-8) vaccination trial was contaminated
      with a BTV-11 virus that was closely related to the Belgian BTV-11 virus from
      2008. This study reports the first complete genome sequences of four BTV-11
      viruses: the BTV-11 contaminant, BTV-11 reference strain, BTV-11 vaccine strain
      and a recently isolated BTV-11 field strain from Martinique. Full-genome analysis
      showed that these viruses belong to serotype 11/nucleotype A and cluster together
      with other western topotype bluetongue viruses. Detailed comparisons of the
      genomes further indicated that the contaminant was derived from the BTV-11
      reference strain, as they were distinguished by a single synonymous nucleotide
      substitution. The previously reported partial sequence of genome segment 2 of the
      Belgian BTV-11 was found to be identical to that of the BTV-11 vaccine strain,
      indicating that it most likely was the BTV-11 vaccine strain. These findings also
      suggest that the BTV-11 contaminant and the Belgian BTV-11 are not the same
      viruses. Finally, comparison of the reference and vaccine strain did not allow
      determining the amino acid substitutions that contribute to the attenuated
      phenotype.

PMID- 24750583
TI  - Clinical usefulness of fracture site in situ block on lumbar spine transverse
      process fracture.
AB  - Lumbar spine transverse process fractures (LSTPFs) are uncommon and frequently
      overlooked on plain film radiographs. Even when recognized, they are often
      regarded as trivial and minimally painful injuries compared with combined serious
      major abdominal, pelvic, and spinal injuries. Conservative treatments are usually
      offered to patients with LSTPFs. This report presents 4 cases of LSTPFs where
      symptoms did not improve after more than 1 week of conservative management. Local
      anesthetics and steroids were injected directly into the fracture site under
      computed tomography guidance, referred to as a fracture site in situ block, in an
      attempt to accelerate the return to daily lives and professional activities.
      Three of the 4 patients returned to their daily lives almost immediately after
      completing the procedure. Although the procedure was appropriately performed at
      L4, 1 patient still complained of pain. This patient's all films were
      meticulously re-examined, and it was determined that a transverse process
      fracture was present at not only L4 but also L1. This report introduces a method
      of active treatment to help patients with LSTPFs quickly return to their daily
      lives and professional activities. The positive results in these cases suggest
      that fracture site in situ block might be a useful option for treating patients
      with LSTPFs. 

PMID- 24750584
TI  - Shigella spp. with reduced azithromycin susceptibility, Quebec, Canada, 2012
      2013.
AB  - During 2012-2013 in Montreal, Canada, 4 locally acquired Shigella spp. pulse
      types with the mph(A) gene and reduced susceptibility to azithromycin were
      identified from 9 men who have sex with men, 7 of whom were HIV infected.
      Counseling about prevention of enteric sexually transmitted infections might help
      slow transmission of these organisms. 

PMID- 24750585
TI  - Anti-M3 muscarinic acetylcholine receptor antibodies in patients with primary
      biliary cirrhosis.
AB  - AIM: M3 muscarinic acetylcholine receptor (M3R) is expressed in biliary tracts as
      well as in exocrine glands. It is reported that some patients with primary
      biliary cirrhosis (PBC) carry autoantibodies against M3R. The aim of this study
      is to clarify the presence, potential use as diagnostic marker and clinical roles
      of anti-M3R antibodies in PBC. METHODS: We synthesized peptides encoding the
      extracellular domains of human-M3R, including the N-terminal region, the first,
      second and third extracellular loops. Antibodies against these regions were
      examined by peptide-based enzyme-linked immunoassay in sera of 90 patients with
      PBC and 40 with chronic hepatitis C (CHC), 21 with non-alcoholic steatohepatitis
      (NASH), 10 with primary sclerosing cholangitis (PSC), 14 with obstructive
      jaundice, 10 with drug-induced liver injury and 42 healthy controls. RESULTS:
      Antibodies to the N-terminal, first, second and third loop were detected in 90.0%
      (81/90), 73.3% (66/90), 76.7% (69/90) and 66.7% (60/90) of PBC, in 67.5% (27/40),
      10.0% (4/40), 67.5% (27/40) and 27.5% (11/40) of CHC, in 85.7% (18/21), 9.5%
      (2/21), 4.8% (1/21) and 57.1% (12/21) of NASH, in 60.0% (6/10), 20.0% (2/10),
      60.0% (6/10) and 60.0% (6/10) of PSC, in 100.0% (14/14), 0% (0/14), 64.3% (9/14)
      and 78.6% (11/14) of obstructive jaundice, in 100.0% (10/10), 0% (0/10), 30.0%
      (3/10) and 10.0% (1/10) of drug-induced liver injury, and in 4.8% (2/42), 7.1%
      (3/42), 2.4% (1/42) and 2.4% (1/42) of the controls, respectively. CONCLUSION: A
      high frequency of PBC carried anti-M3R antibodies. Anti-M3R antibodies against
      the first loop of M3R are a potentially useful diagnostic marker for PBC.

PMID- 24750586
TI  - Economic burden of influenza-associated hospitalizations and outpatient visits in
      Bangladesh during 2010.
AB  - OBJECTIVE: Understanding the costs of influenza-associated illness in Bangladesh
      may help health authorities assess the cost-effectiveness of influenza prevention
      programs. We estimated the annual economic burden of influenza-associated
      hospitalizations and outpatient visits in Bangladesh. DESIGN: From May through
      October 2010, investigators identified both outpatients and inpatients at four
      tertiary hospitals with laboratory-confirmed influenza infection through rRT-PCR.
      Research assistants visited case-patients' homes within 30 days of hospital
      visit/discharge and administered a structured questionnaire to capture direct
      medical costs (physician consultation, hospital bed, medicines and diagnostic
      tests), direct non-medical costs (food, lodging and travel) and indirect costs
      (case-patients' and caregivers' lost income). We used WHO-Choice estimates for
      routine healthcare service costs. We added direct, indirect and healthcare
      service costs to calculate cost-per-episode. We used median cost-per-episode,
      published influenza-associated outpatient and hospitalization rates and
      Bangladesh census data to estimate the annual economic burden of influenza
      associated illnesses in 2010. RESULTS: We interviewed 132 outpatients and 41
      hospitalized patients. The median cost of an influenza-associated outpatient
      visit was US$4.80 (IQR = 2.93-8.11) and an influenza-associated hospitalization
      was US$82.20 (IQR = 59.96-121.56). We estimated that influenza-associated
      outpatient visits resulted in US$108 million (95% CI: 76-147) in direct costs and
      US$59 million (95% CI: 37-91) in indirect costs; influenza-associated
      hospitalizations resulted in US$1.4 million (95% CI: 0.4-2.6) in direct costs and
      US$0.4 million (95% CI: 0.1-0.8) in indirect costs in 2010. CONCLUSIONS: In
      Bangladesh, influenza-associated illnesses caused an estimated US$169 million in
      economic loss in 2010, largely driven by frequent but low-cost outpatient visits.

PMID- 24750588
TI  - Detailed investigation of ongoing subclinical hepatitis E virus infections;
      occurring in outbreak settings of North India.
AB  - BACKGROUND & AIMS: Every year globally WHO reports 20 million Hepatitis E virus
      (HEV) infections. The disease occurs as sporadic cases or focused outbreaks and
      has potentials to cause massive epidemics. The reservoir of HEV during inter
      epidemic period is not well characterized. The sporadic cases usually lack
      history of contact with clinically overt HEV patients. In the present context we
      evaluated the occurrence of subclinical HEV as a possible reservoir in endemic
      region. METHODS: Blood samples were collected from 67 apparently healthy
      individuals and 10 acute viral hepatitis (AVH) patients during two HEV outbreaks
      in North India. The serum samples were tested for anti-HEV IgM, IgG, HEV-IgG
      avidity index, HEV viral load and conventional-PCR followed by sequencing and
      phylogenetic analysis. RESULTS: A total of 14 (20.89%) apparently healthy
      individuals showed the presence of anti-HEV IgM and IgG. Of 14 based on HEV-IgG
      avidity index, 9 (64.28%) had secondary-exposure, 4 (28.57%) had primary
      exposure, while one patient had intermediate avidity. Subclinical subjects with
      primary exposure had significantly higher anti-HEV IgM index as compared to
      secondary-exposure (P = 0.0028). Viral load in clinically jaundiced patients was
      significantly higher as compared to subclinical subjects (P < 0.0001).
      Phylogenetic analysis showed HEV sequences retrieved from subclinical individuals
      clustered along with AVH patients, suggesting matched source. The significantly
      low viral load in subclinical subjects hints towards the dose dependency for
      progression of clinical manifestation. CONCLUSION: We document subclinical HEV
      with low level viremia occurs during outbreak settings and goes un-noticed, which
      helps maintaining the virus in nature possibly leading to its endemicity.

PMID- 24750587
TI  - L-arginine conjugates of bile acids-a possible treatment for non-alcoholic fatty
      liver disease.
AB  - BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is a continuum of diseases
      that include simple steatosis and non-alcoholic steatohepatitis (NASH) ultimately
      leading to cirrhosis, hepatocellular carcinoma and end stage liver failure.
      Currently there is no approved treatment for NASH. It is known that bile acids
      not only have physiological roles in lipid digestion but also have strong
      hormonal properties. We have synthesized a novel chenodeoxycholyl-arginine ethyl
      ester conjugate (CDCArg) for the treatment of NAFLD. METHODS: Chemical synthesis
      of CDCArg was performed. Experiments for prevention and treatment of NAFLD were
      carried out on C57BL/6 J male mice that were treated with high fat diet (HFD, 60%
      calories from fat). CDCArg or cholic acid bile acids were admixture into the
      diets. Food consumption, weight gain, liver histology, intraperitoneal glucose
      tolerance test, biochemical analysis and blood parameters were assessed at the
      end of the experiment after 5 weeks of diet (prevention study) or after 14 weeks
      of diet (treatment study). In the treatment study CDCArg was admixture into the
      diet at weeks 10-14. RESULTS: In comparison to HFD treated mice, mice treated
      with HFD supplemented with CDCArg, showed reduced liver steatosis, reduced body
      weight and decreased testicular fat and liver tissue mass. Blood glucose,
      cholesterol, insulin and leptin levels were also lower in this group. No evidence
      of toxicity of CDCArg was recorded. In fact, liver injury, as evaluated using
      plasma hepatic enzyme levels, was low in mice treated with HFD and CDCArg when
      compared to mice treated with HFD and cholic acid. CONCLUSION: CDCArg
      supplementation protected the liver against HFD-induced NAFLD without any toxic
      effects. These results indicate that basic amino acids e.g., L-arginine and bile
      acids conjugates may be a potential therapy for NAFLD.

PMID- 24750589
TI  - Consequences of long-term discontinuation of vascular endothelial growth factor
      inhibitor therapy in the patients with neovascular age-related macular
      degeneration.

PMID- 24750590
TI  - Three-dimensional microvasculature in rat and human hearts using a non-injection
      Ca2+-ATPase method on thick and ultra-thick sections.
AB  - Currently there are no methods available for staining rat and human myocardial
      microvasculature on thick sections that would allow for specific staining and
      differentiation of arterioles, venules, and capillaries. A non-injection
      technique is described that allows for labeling of the microvascular bed (MVB) in
      formalin-fixed pieces of the myocardium from humans and the white rat Rattus
      norvegicus, as well as human full-mount pericardium. Vessel staining is based on
      the activity of phosphatases (ATPases) and the precipitation of the released
      phosphate with calcium ions at high pH (pH 10.5-11.5). The resulting precipitate
      subsequently is converted to black or brown lead sulfide. The specificity of this
      reaction to vessels of the MVB allows arterioles, venules, capillaries, and pre-
      and postcapillaries to be clearly visualized in thick (60-100 um) and ultra-thick
      (300-500 um) sections against an unstained background of muscle and connective
      tissue. In addition, smooth muscle cells of arterioles are also stained allowing
      for differentiation between arteriolar and venular beds. These observations have
      not been reported in rat or human myocardium using other methods. This procedure
      should benefit studies of coronary microcirculation in experimental and
      pathological conditions, as well as in pharmacological investigations. 

PMID- 24750591
TI  - Phosphotriesterase-related protein sensed albuminuria and conferred renal tubular
      cell activation in membranous nephropathy.
AB  - BACKGROUND: Membranous nephropathy (MN) is a common cause of nephrotic syndrome
      that may progress to end-stage renal disease (ESRD). The formation of MN involves
      the in situ formation of subepithelial immune deposits and leads to albuminuria;
      however, the underlying mechanism of how MN leads to ESRD remains unclear. The
      aim of this study was to investigate the expression and biological functions of
      phosphotriesterase-related protein (PTER) in MN. RESULTS: In the progression of
      MN, the expression of PTER increased significantly and was mainly expressed in
      the renal tubular cells. Both mRNA and protein expression levels of PTER were
      increased in a concentration- and time-dependent manner in the in vitro
      albuminuria tubular cell model. Silencing the expression of PTER by RNA
      interference diminished albuminuria-induced inflammatory and pro-fibrotic
      cytokines production. CONCLUSIONS: Our findings reveal that PTER may sense
      albuminuria in the progression of MN, induce tubular cell activation and lead to
      ESRD.

PMID- 24750592
TI  - Extended-spectrum beta-lactamases in Escherichia coli and Klebsiella pneumoniae
      in Gulls, Alaska, USA.

PMID- 24750593
TI  - Global Health Care Justice, Delivery Doctors and Assisted Reproduction: Taking a
      Note From Catholic Social Teachings.
AB  - This article will examine the Catholic concept of global justice within a health
      care framework as it relates to women's needs for delivery doctors in the
      developing world and women's demands for assisted reproduction in the developed
      world. I will first discuss justice as a theory, situating it within Catholic
      social teachings. The Catholic perspective on global justice in health care
      demands that everyone have access to basic needs before elective treatments are
      offered to the wealthy. After exploring specific discrepancies in global health
      care justice, I will point to the need for delivery doctors in the developing
      world to provide basic assistance to women who hazard many pregnancies as a
      priority before offering assisted reproduction to women in the developed world.
      The wide disparities between maternal health in the developing world and elective
      fertility treatments in the developed world are clearly unjust within Catholic
      social teachings. I conclude this article by offering policy suggestions for
      moving closer to health care justice via doctor distribution. 

PMID- 24750594
TI  - Influenza A(H5N2) virus antibodies in humans after contact with infected poultry,
      Taiwan, 2012.
AB  - Six persons in Taiwan who had contact with poultry infected with influenza
      A(H5N2) showed seroconversion for the virus by hemagglutinin inhibition or
      microneutralization testing. We developed an ELISA based on nonstructural protein
      1 of the virus to differentiate natural infection from cross-reactivity after
      vaccination; 2 persons also showed seroconversion by this test. 

PMID- 24750595
TI  - Investigation of silver nanoparticles synthesis using aminated beta-cyclodextrin.
AB  - Aminated beta-cyclodextrin was prepared through the reaction of 2
      chloroethylamine with beta-cyclodextrin. The preparation was carried out under
      different conditions (time, temperature, concentration of NaOH, and concentration
      of 2-chloroethylamine). The aminated beta-cyclodextrin was used as reducing and
      stabilizing agent for the preparation of silver nanoparticles from AgNO3. Factors
      (pH, temperature, time, extent of amination and concentration of aminated beta
      cyclodextrin) affecting the preparation of silver nanoparticles were studied. The
      prepared silver nanoparticles were evaluated by UV-visible spectral analysis and
      transmission electron microscopy (TEM). The results obtained indicate that the
      optimum conditions for preparation of silver nanoparticles with size ranged from
      1 to 9 nm could be produced using 0.6 g beta-cyclodextrin derivative, 0.1 M AgNO3
      at pH 12, 70  degrees C for 20 min.

PMID- 24750596
TI  - Theoretical and experimental investigation on dissolution and regeneration of
      cellulose in ionic liquid.
AB  - Density functional theory calculations and atoms in molecules theory were
      performed to investigate the mechanism of cellulose dissolution and regeneration
      in 1-ethyl-3-methylimidazolium acetate ([emim]Ac), and (1,4)-dimethoxy-beta-D
      glucose (Glc) was chosen as the model for cellulose. The theoretical results show
      that the interaction of [emim]Ac with Glc is stronger than that of Glc with Glc.
      Further studies indicate that the anion acetate of [emim]Ac forms strong H-bonds
      with hydroxyl groups of Glc. It is also observed that the H-bonds between
      [emim]Ac and Glc are weakened or even destroyed by the addition of water. In
      addition, both the original and regenerated cellulose samples were characterized
      with FT-IR, XRD, TGA and SEM. The experimental results prove that cellulose can
      be readily reconstituted from the [emim]Ac-based cellulose solution by the
      addition of water and the crystalline structure of cellulose is converted to
      cellulose II from cellulose I in the original cellulose. 

PMID- 24750597
TI  - Fermentation optimization, characterization and bioactivity of exopolysaccharides
      from Funalia trogii.
AB  - Optimization of culture conditions for exopolysaccharide (EPS) by Funalia trogii
      in submerged culture was investigated using one-factor-at-a-time method and
      uniform design (UD). Under the optimized conditions, the maximum concentration of
      EPS was 8.68 g/l. After EPS was deproteinized by Sevag method, two groups of EPSs
      (designated as Fr-I and Fr-II) were obtained from the culture filtrates by gel
      filtration chromatography on Sepharose CL-6B. Furthermore, EPSs were
      characterized by size exclusion chromatography (SEC) coupled with a multiangle
      laser-light scattering (MALLS) and refractive index (RI) detector system. The
      weight-average molar masses of the Fr-I and Fr-II were determined to be 1.007 *
      10(5) and 2.393 * 10(4)g/mol, respectively. The root mean square (RMS) radii for
      both peaks ranged from 9.7 to 10.8 nm with no clear trends. Pharmacology
      experiments indicated F. trogii EPS were useful to the therapy of free radical
      injury and cancer diseases.

PMID- 24750598
TI  - Interaction between xanthan gum and cationic cellulose JR400 in aqueous solution.
AB  - The electrostatic and hydrogen bonding interactions between xanthan gum (XG) and
      semisynthetic cationic cellulose (JR400) in aqueous solution are investigated via
      stability map, FT-IR spectra, thermogravimetric analysis, potentiometric
      measurement and rheological method. The stability map shows three regions, a
      stable region with XG as the major component, a flocculated region and another
      stable region with JR400 as the major component. The stability of mixing system
      depends on both the concentration fraction of JR400 (fJR) and the overlapping
      concentrations of these two polymers. In the region near the stoichiometric fJR,
      the mixture shows stoichiometric flocculation, which is independent of the total
      polymer concentration. However, in the regions away from the stoichiometric fJR,
      the mixtures are stable when the concentration of major polymer component is
      higher than its overlapping concentration. In stable regions, the electrostatic
      and hydrogen bonding interactions can enhance the viscosity of mixing system at
      appropriate fJR values. 

PMID- 24750599
TI  - Purification of a polysaccharide from Boschniakia rossica and its synergistic
      antitumor effect combined with 5-Fluorouracil.
AB  - Current study we purified a polysaccharide (BRP) from Boschniakia rossica and the
      antitumor effects of BRP alone or combined with 5-Fluorouracil (5-FU) was
      examined in S180 tumor bearing mice by intragastric administration. The high
      performance size-exclusion chromatography (HPGEC) analysis showed that BRP was a
      homogeneous polysaccharide and had a molecular weight of 2.2 * 10(4) Da. Total
      carbohydrate content in BRP was determined to be 96.9%, without the presence of
      protein and nucleic acid. BRP alone or combined with 5-FU could significantly
      inhibit Sarcoma-180 (S180) tumor growth and increase the spleen index in a dose
      dependent manner. Meanwhile a synergistic effect was observed in boosting various
      immunity functions when the tumor bearing mice receiving BRP plus 5-FU
      administration, such as stimulating lymphocytes proliferation, increasing NK cell
      cytotoxicity, enhancing serum interleukin-2 (IL-2) and interferon-gamma (TNF
      gamma) secretion, as well as augmenting CD4+ and CD8+ spleen T lymphocytes
      subsets. The results showed that BRP combined with 5-FU presented synergistic
      effects on antitumor activity in tumor bearing mice. In conclusion, the
      combination of BRP may boost the suppressed immunity in tumor bearing mice
      subject to 5-FU chemotherapy, and could serve as a new, promising approach for
      cancer treatment.

PMID- 24750600
TI  - Preparation and characterization of self-emulsified waterborne nitrocellulose.
AB  - Waterborne nitrocellulose (WNC) dispersion was successfully synthesized by self
      emulsification and reaction among isophorone diisocyanate (IPDI), dimethylol
      propionic acid (DMPA) and nitrocellulose (NC). The WNC was characterized by
      transmission electron microscopy (TEM), Fourier transform infrared (FTIR)
      spectroscopy and thermal gravimetric analysis (TGA), etc. The WNC dispersion has
      Z-average particle size of 133 nm approximately and distribution index of 0.152.
      It is indicated by TEM that the cured WNC particles show a core-shell structure,
      in which hydrophobic component is encapsulated by the hydrophilic carboxyl. FTIR
      confirms that the reactions (i.e. IPDI and NC, IPDI and DMPA) have occurred, the 
      NCO group of IPDI has been consumed totally and the backbone of NC is retained.
      TGA reveals that the cross-linked WNC film has better thermal resistance, and the
      water resistance measurement confirms that it has weaker water-sensitivity.

PMID- 24750601
TI  - Construction of the highly secreted endochitinase Pichia pastoris strain and the
      optimization of chitin-degrading conditions.
AB  - The endochitinase has a very important application in the preparation of
      bioactive chitooligosaccharides by chitin degradation. In this paper, the mature
      endochitinase cDNA from Trichoderma sp. was overexpressed in Pichia pastoris
      GS115 in order to enhance its activity. The screened recombinant strain could
      secrete the endochitinase into the culture broth highly on induction with
      methanol of 0.5%. The activity of the endochitinase was up to 89.3 U/mL,
      corresponding to its concentration of 365 mg/L, at 72 h after induction. The
      optimal chitin-degrading conditions with it were as follows: powder chitin
      concentration 4%, pH 7.0 and temperature 30  degrees C. Under above conditions,
      the content of the reducing sugar obtained was up to 398.4 MUg/mL at 10 h. These
      results indicated that the expressed endochitinase exhibited an exceptionally
      excellent chitin-degrading ability, and could be used for the preparation of
      bioactive chitooligosaccharides in future.

PMID- 24750602
TI  - The target gene carrying validity to HePG2 cells with the brush-like glutathione
      modified chitosan compound.
AB  - The grafting modified chitosan with L-glutathione (GSH) end capped PEG brush-like
      poly [poly(ethylene glycol) methacrylate] (PMPEG), CS-PMPEG-GSH, as the pDNA
      condensed vector material could result in a much higher transfection efficiency
      and lower cytotoxity for NIH3T3 cells. In this work, we have further examined the
      morphology stabilities of CS-PMPEG-GSH/pDNA vectors at different medium pH values
      and in the presence of serum protein in detail. And then the targeted characters
      for HepG2 cells have been probed by tracing the cell uptake behavior and
      transfection efficiency.

PMID- 24750603
TI  - Influence of heating time and pressure treatment of potato starch on the
      generation of radicals: EPR studies.
AB  - The influence of heating time and pressurizing time under pressure of 1 GPa on
      radicals generation in potato starch polymer was investigated by EPR. Potato
      starch was heated at two temperatures: 413 +/- 2 K (140  degrees C) and 473 +/- 2
      K (200  degrees C) for 15, 30, 60, 120, 180, 240, 270 and 300 min and subdued to
      pressurizing under pressure of 1 +/- 0.002 GPa for 6, 60, 300 and 1440 min. In
      starch heated at 413 K (140  degrees C) a decrease in the relative intensity of
      the EPR signal as a function of the pressurizing time can be observed, whereas in
      starch heated at 473 K (200  degrees C) such a decrease is not observed. The EPR
      spectra analysis indicates that they are powder spectra due to the paramagnetic
      centers leading to Lorentzian line shapes with weak spectroscopic splitting
      factor g anisotropies and linewidth anisotropies. We have shown that
      pressurization of starch causes a decrease in the number of radicals in a
      temperature range in which the polymer is not yet disintegrated. The results of
      the EPR investigations indicate the existence of a carbon radical center situated
      at the carbon C1 of the glucose ring. In the EPR spectra of the samples heated
      with no oxygen access, the hyperfine structure is poorly visible. In the
      registered EPR spectra of the samples heated with oxygen access, the hyperfine
      structure is not observed.

PMID- 24750604
TI  - Isolation, purification and antioxidant activities of polysaccharides from
      Grifola frondosa.
AB  - The crude polysaccharides (GFP) were isolated from the fruiting bodies of Grifola
      frondosa and purified by DEAE cellulose-52 chromatography and Sephadex G-100 size
      exclusion chromatography in that order. Three main fractions, GFP-1, GFP-2 and
      GFP-3, were obtained through the isolation and purification steps. Then the
      antioxidant activities of these three fractions were investigated in vitro. The
      results showed that GFP-1, GFP-2 and GFP-3 possessed significant inhibitory
      effects on 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical, hydroxyl radical and
      superoxide radical; their reducing power, ferrous ions chelating effect and the
      inhibition ability of the rat liver lipid oxidation where also strong. These
      results suggest that G. frondosa polysaccharides could be a suitable natural
      antioxidant and may be the functional foods for humans. 

PMID- 24750605
TI  - Preparation and characterization of regenerated cellulose/poly (vinylidene
      fluoride) (PVDF) blend films.
AB  - Regenerated cellulose/poly (vinylidene fluoride) (PVDF) blend film was
      successfully prepared through coagulating their N,N-dimethyl acetamide
      (DMAC)/LiCl solution with water. The toughness of the blend films, compared with
      virgin regenerated cellulose film, was significantly improved when the content of
      PVDF in blend films was no more than 20 wt.%. The elongation at break increased
      from 12% to 34%, and the tensile strength was also improved from 89 to 106 MPa
      with the addition of PVDF till 20 wt.%. The mechanical properties of the blend
      films became worse when the content of PVDF in blend films was more than 20%. The
      oxygen permeability was firstly decreased from 2.3 1 (-10) to 0.036 1 (
      10)cm(3)cm/cm(2)s Pa when the PVDF content increased from 0 to 5 wt.% in the
      blend films. Afterwards, the oxygen permeability would increase with the
      increasing of the PVDF content. The film showed some pores when the loading level
      of PVDF was more than 50%. The pore size of blend film became larger with the
      increasing of PVDF content. These phenomena were well correlated to the
      crystallinity, hydrogen bonds and morphologies of the blend films.

PMID- 24750606
TI  - Venlafaxine loaded chitosan NPs for brain targeting: pharmacokinetic and
      pharmacodynamic evaluation.
AB  - The purpose of the present investigation was to prepare venlafaxine (VLF) loaded
      chitosan nanoparticles (NPs) to enhance the uptake of VLF to brain via intranasal
      (i.n.) delivery. VLF loaded chitosan NPs were prepared and characterized for
      particle size, size distribution, zeta potential, encapsulation efficiency and in
      vitro drug release. In order to investigate the localization of chitosan NPs in
      brain and other organs qualitatively confocal laser scanning microscopy technique
      was carried out using rhodamine-123 (ROD-123) as marker. The levels of VLF in
      plasma and brain tissues were also determined, the brain/blood ratios of VLF for
      VLF (i.v.), VLF (i.n.), VLF chitosan NPs (i.n.) were 0.0293, 0.0700 and 0.1612,
      respectively, at 0.5h, indicative of better brain uptake of VLF chitosan NPs. The
      higher drug transport efficiency (508.59) and direct transport percentage (80.34)
      of VLF chitosan NPs as compared to other formulations suggest its better efficacy
      in treatment of depression. 

PMID- 24750607
TI  - Cellulose micro/nanofibres from Eucalyptus kraft pulp: preparation and
      properties.
AB  - There is growing interest in cellulose nanofibres from renewable sources for
      several industrial applications. However, there is a lack of information about
      one of the most abundant cellulose pulps: bleached Eucalyptus kraft pulp. The
      objective of the present work was to obtain Eucalyptus cellulose micro/nanofibres
      by three different processes, namely: refining, sonication and acid hydrolysis of
      the cellulose pulp. The refining was limited by the low efficiency of isolated
      nanofibrils, while sonication was more effective for this purpose. However, the
      latter process occurred at the expense of considerable damage to the cellulose
      structure. The whiskers obtained by acid hydrolysis resulted in nanostructures
      with lower diameter and length, and high crystallinity. Increasing hydrolysis
      reaction time led to narrower and shorter whiskers, but increased the
      crystallinity index. The present work contributes to the different widespread
      methods used for the production of micro/nanofibres for different applications. 

PMID- 24750608
TI  - Inclusion complex of GA-13315 with cyclodextrins: preparation, characterization,
      inclusion mode and properties.
AB  - GA-13315 (13-chlorine-3,15-dioxy-gibberllic acid methyl ester) was semi
      synthesized by GA3 (gibberellic acid) as a potential anticancer drug. To pursue
      its promising application, cyclodextrin was used for forming complexes to
      overcome its drawbacks such as poor water solubility and stability. So, GA
      13315/CD complexes were prepared with native beta-cyclodextrin and its
      derivatives (hydroxypropyl-beta-cyclodextrin (HPbetaCD)) and their inclusion
      complexation behavior, characterization and binding ability in both solution and
      the solid state was studied by means of UV, XRD, DSC, SEM, (1)H and 2D NMR
      spectroscopy. Furthermore, preliminary in vitro cytotoxicity assay showed that
      the complexes still maintain antitumor activities, compared with GA-13315 or
      adriamycin (ADM, positive control) as the positive control. The results showed
      that the water solubility and stability of GA-13315 were obviously improved in
      the inclusion complex with cyclodextrins, suggesting the inclusion complexes as
      promising future therapeutic agents. 

PMID- 24750609
TI  - On the interaction between konjac glucomannan and xanthan in mixed gels: an
      analysis based on the cascade model.
AB  - The rheological properties and critical behavior of konjac glucomannan
      (KGM)/xanthan (XG) mixed gels were investigated and analyzed using a two
      component cascade model. The fitting results show that the optimal functionality
      value for KGM (fKGM) is 3, whereas the possible functionality value for XG (fXG)
      is 100-1000 obtained from the modulus data, or 25 obtained from the critical
      data. The van't Hoff analysis of the critical data shows that the binding of KGM
      with XG has a high enthalpy/entropy ratio (DeltaH/300DeltaS=5.52), which can be
      explained by the gain in the hydrational entropy due to the release of water
      molecules during the binding reaction. From these results, we proposed that the
      binding of KGM with XG takes place on the consecutive glucose residues of KGM
      with six or more units. 

PMID- 24750610
TI  - Study on antibacterial activity of O-carboxymethyl chitosan sodium salt and
      spinnability of O-carboxymethyl chitosan sodium salt/cellulose polyblends in N
      methylmorpholine-N-oxide system.
AB  - O-carboxymethyl chitosan sodium salt (NaCMCh), which has good antibacterial
      activity and solubility in N-methylmorpholine-N-oxide (NMMO) after being treated
      by sodium hydroxide solution, was blended with cellulose NMMO/H2O solution to
      study the spinnability. The effect of molecular weight on antibacterial activity
      and solubility was discussed. The optimal range of molecular weights is from 8 x
      104 to 1.9 x 105). The rheological properties of NaCMCh/cellulose polyblends in
      steady-shear were investigated. The results are presented using appropriate
      master curves for the temperature and concentration effects. The flow behavior
      index of the polyblends increase with increasing temperature and NaCMCh content.
      Apparent viscosity and zero-shear viscosity decrease, but the critical shear rate
      increases due to the addition of NaCMCh. The polyblends with NaCMCh display a
      lower structural viscosity index. Finally, the fibers were successfully spun
      using the lyocell process with NMMO/H2O and the fibers with NaCMCh exhibit good
      mechanical properties and moisture absorption.

PMID- 24750611
TI  - Characterization and antibacterial properties of genipin-crosslinked
      chitosan/poly(ethylene glycol)/ZnO/Ag nanocomposites.
AB  - Novel nanocomposites consisting of genipin-crosslinked chitosan (GC),
      poly(ethylene glycol) (PEG), zinc oxide (ZnO), and silver (Ag) nanoparticles were
      prepared for biomedical applications as the wound-healing materials. Various
      amounts of ZnO and Ag nanoparticles were dispersed in the GC/PEG hydrogel matrix
      without severe aggregation. The effects of composition and ZnO nanoparticles on
      the physico-chemical properties of nanocomposite samples were evaluated by
      infrared analysis, X-ray diffraction, and scanning electron microscopy.
      GC/PEG/ZnO/Ag nanocomposite showed the pH-sensitive swelling behavior and the
      improved mechanical properties. The antibacterial activities of nanocomposite
      films were tested toward the bacterial species Escherichia coli, Pseudomonas
      aeruginosa, Staphylococcus aureus, and Bacillus subtilis. GC/PEG/ZnO/Ag composite
      films had higher antibacterial activities than GC/PEG and GC/PEG/ZnO
      nanocomposite films. GC/PEG/ZnO/Ag composite films have potential application as
      wound and burn dressings. 

PMID- 24750612
TI  - Glucose-responsive insulin delivery microhydrogels from methacrylated
      dextran/concanavalin A: preparation and in vitro release study.
AB  - Glucose-responsive systems are very important for self-regulated insulin
      delivery. The aim of the present study was to evaluate the potential of insulin
      loaded microhydrogels fabricated from methacrylate derivatives of dextran (Dex-G)
      and concanavalin A (Con A-E) as a insulin delivery system releasing insulin in
      response to different glucose levels. Insulin-loaded microhydrogels were prepared
      through a reversed-phase emulsion crosslinking method. The morphology and size of
      obtained microhydrogels were characterized by SEM, fluorescence microscope and
      dynamic light scattering, which showed that these microhydrogels were formed with
      sphere-like shape and diameters less than 5 MUm. In vitro release of insulin from
      these microhydrogels and release kinetics were studied. The results indicated
      that insulin release was reversible in response to different glucose
      concentrations and the released insulin was shown to remain active since the
      tertiary structure was not destroyed. The degree of substitution (DS) of dextran
      methacrylate derivatives had effects on the release rate and surface burst
      release of the microhydrogels and high DS of Dex-G (DS 32) restricted the glucose
      sensitivity of the microhydrogels. The MTT assay from L929 cell line indicated
      that these microhydrogels possessed noncytotoxicity. The results suggested that
      these microhydrogels might be suitable for self-regulated insulin delivery and
      find potential applications in biomedical fields.

PMID- 24750614
TI  - Pectins filled with LDH-antimicrobial molecules: preparation, characterization
      and physical properties.
AB  - Nanohybrids of layered double hydroxide (LDH) with intercalated active molecules:
      benzoate, 2,4-dichlorobenzoate, para-hydroxybenzoate and ortho-hydroxybenzoate,
      were incorporated into pectins from apples through high energy ball milling in
      the presence of water. Cast films were obtained and analysed. X-ray diffraction
      analysis showed a complete destructuration of all nanohybrids in the pectin
      matrix. Thermogravimetric analysis showed a better thermal resistance of pectin
      in the presence of fillers, especially para-hydroxybenzoate and ortho
      hydroxybenzoate. Mechanical properties showed an improvement of elastic modulus
      in particular for LDH-para-hydroxybenzoate nanohybrid, due probably to a better
      interaction between pectin matrix and nanohybrid layers. Barrier properties
      (sorption and diffusion) to water vapour showed improvement in the dependence on
      the intercalated active molecule, the best improvement was achieved for
      composites containing para-hydroxybenzoate molecules, suggesting that the
      interaction between the filler phase and the polymer plays an important role in
      sorption and diffusion phenomena. Incorporation of these active molecules gave
      antimicrobial properties to the composite films giving opportunities in the field
      of active packaging. 

PMID- 24750613
TI  - pH- and glucose-sensitive glycopolymer nanoparticles based on phenylboronic acid
      for triggered release of insulin.
AB  - Amphiphilic poly(acrylic acid-co-acrylamidophenylboronic acid)-block-poly(2
      acryloxyethyl galactose)-block-poly(acrylic acid-co-acrylamidophenylboronic acid)
      (((PAA-co-PAAPBA)-b-)2PAEG) copolymer was fabricated: The poly(2-acryloyloxyethyl
      pentaacetylgalactoside) (PAEAcG) with narrow molecular weight distributions
      (Mw/Mn<=1.22) was prepared by atom transfer radical polymerization (ATRP) using
      dibromo-p-xylene (DBX) as initiator. Then the well-defined triblock copolymer
      poly(t-butyl acrylate)-b-poly(2-acryloyloxyethyl pentaacetylgalactoside)-b-poly(t
      butyl acrylate) (PtBA-b-PAEAcG-b-PtBA) was synthesized by ATRP of tBA using
      PAEAcG homopolymer with dibromo end groups as macroinitiator. After hydrolysis of
      t-butyl acrylate block, amide linkage and deacetylation, the final copolymer
      ((PAA-co-PAAPBA)-b-)2PAEG was obtained. Because of characteristics of three
      different segments, amphiphilic ((PAA-co-PAAPBA)-b-)2PAEG can self-assemble into
      pH- and glucose-responsive nanoparticles studied by dynamic light scattering
      (DLS) and transmission electron microscopy (TEM). Furthermore, the in vitro
      release profiles of insulin also revealed obvious pH- and glucose-sensitivity of
      the nanoparticles. The analysis of cell viability suggested that the copolymer
      nanoparticles had good cytocompatibility.

PMID- 24750616
TI  - Synthesis of nano cellulose fibers and effect on thermoplastics starch based
      films.
AB  - Starch based films limit their application due to highly hydrophilic nature and
      poor mechanical properties. This problem was sought to be overcome by forming a
      nanocomposite of Thermoplastic starch (TPS) and Nano-Cellulose fibers (NCF). NCF
      was successfully synthesised from short stable cotton fibres by a chemo
      mechanical process. TPS/NCF composite films were prepared by solution casting
      method, and their characterizations were done in terms of differential scanning
      calorimeter (DSC), morphology (SEM), water vapor permeability (WVTR), oxygen
      transmission rate (OTR), X-ray diffractograms, light transmittance and tensile
      properties. At very low concentration of NCF filled TPS composite film showed
      improvement in properties. The 0.4 t% NCF loaded TPS films showed 46.10% improved
      tensile strength than by base polymer film, beyond that 0.5 t% concentration
      tensile strength starts to deteriorate. WVTR and OTR results showed improved
      water vapor barrier property of TPS matrix. The DSC thermograms of TPS and
      composite films did not show any significant effect on the melting point of
      composite film to the base polymer TPS.

PMID- 24750615
TI  - The effect of nanoparticles on gastrointestinal release from modified kappa
      carrageenan nanocomposite hydrogels.
AB  - In this article, silver and magnetite nanofillers were synthesized in modified
      kappa-carrageenan hydrogels using the in situ method. The effect of metallic
      nanoparticles in gastro-intestinal tract (GIT) release of a model drug (methylene
      blue) has been investigated. The effect of nanoparticles loading and genipin
      cross-linking on GIT release of nanocomposite is also studied to finally provide
      the most suitable drug carrier system. In vitro release studies revealed that
      using metallic nanocomposites hydrogels in GIT studies can improve the drug
      release in intestine and minimize it in the stomach. It was found that cross
      linking and nanofiller loading can significantly improve the targeted release.
      Therefore, applying metallic nanoparticles seems to be a promising strategy to
      develop GIT controlled drug delivery. 

PMID- 24750617
TI  - Novel hydrophobic hemicelluloses: synthesis and characteristic.
AB  - Novel hydrophobic hemicelluloses possessing hydrophobic groups were prepared by
      the benzylation of wheat straw hemicelluloses with benzyl chloride under the
      presence of catalyst in an ethanol/water system. In particular, the progress of
      the benzylation reaction was studied as a function of the volume ratio of
      ethanol/water from 4:1 to 6:4, the molar ratio of NaOH/anhydroxylose unit in
      hemicelluloses from 0.6:1 to 1.5:1, the molar ratio of benzyl
      chloride/anhydroxylose unit in hemicelluloses from 0.5:1 to 2.0:1, reaction
      temperature 50-80  degrees C, and reaction time 4-20 h Benzylated hemicelluloses
      with the low degree of substitution from 0.09 to 0.35 were obtained depending on
      the experimental conditions. The incorporation of benzyl groups into the backbone
      of hemicelluloses was confirmed by FT-IR and (13)C NMR spectroscopies. The
      thermal stability increased after the modification of hemicelluloses due to the
      introduction of benzyl groups. The introduction of benzyl groups endows
      hemicelluloses with the hydrophobicity, which could be potentially applied in
      plastic industries.

PMID- 24750618
TI  - Controlled acetylation of water-soluble glucomannan from Bletilla striata.
AB  - Glucomannans from Bletilla striata (bletillan) were used as excipient for
      controlled deliveries of drugs, genes and tissue engineering. In the present
      study, a controlled acetylation method was developed to improve water solubility
      of bletillan 70 (BT) firstly, by reacting with acetic anhydride (AA) in N,N
      dimethylformamide solvent. The preparation parameters, such as reaction
      temperature, reaction time and molar ratio of BT/AA, were optimized based on
      degrees of acetyl group in addition. IR and (1)H NMR spectra were applied to
      elucidate the reaction process and substitution pattern, which indicated that the
      acetylation took place at C-6 and C-2 of the hexose units in a ratio of 2:1, with
      DS up to 0.83. Relative viscosity analysis revealed that the resulted products
      had improved water solubilities. This novel method is simple, economic and easily
      controlled. 

PMID- 24750619
TI  - Synthesis and characterization of cationically modified nanocrystalline
      cellulose.
AB  - In this study, nanocrystalline cellulose (NCC) resulting from sulfuric acid
      hydrolysis of wood cellulose fiber, was rendered cationic by grafting with
      glycidyltrimethylammonium chloride (GTMAC). An optimization of the reaction
      parameters, such as water content, reactant mole ratio, and reaction media was
      performed. The presence of cationic GTMAC on the surface of NCC was confirmed by
      Fourier Transform Infrared Spectroscopy (FTIR). The cationically modified NCC was
      characterized by surface charge density, degree of substitution, zeta potential,
      and particle size. It was found that the cationic surface charge density of NCC
      can be increased by controlling the water content of the reaction system. Surface
      cationization of NCC led to an increase in the surface charge density over the un
      modified NCC. The cationically modified NCC was well dispersed and stable in
      aqueous media due to enhanced cationic surface charge density. Transmission
      electron microscopy (TEM) images showed the improvement in state of dispersion of
      cationically modified NCC over the un-modified NCC. The optimum water content was
      found to be 36 wt% for aqueous based media and 0.5 water to DMSO volume ratio for
      aqueous-organic solvent reaction media. The increased surface charge density of
      NCC also delayed the onset of gelation in aqueous system.

PMID- 24750620
TI  - The adsorptive and hydrolytic performance of cellulase on cationised cotton.
AB  - In this research, the cotton fabrics were cationised by a cationic agent to
      change their surface electric properties. The cationised cotton fabrics were then
      bio-polished by cellulase to explore the influence of cationisation on the
      adsorptive and hydrolytic performance of cellulase. The experimental results from
      cellulase adsorption reveal the cationisation of cotton can obviously improve the
      binding efficiency of cellulase protein mainly by the improved electrostatic
      attraction between oppositely charged cellulase and cationised cotton. The
      adsorption parameters calculated can further prove this improvement trend.
      Through measuring the concentration of reducing sugars released and weight loss
      of cotton during the bio-polishing, it is found the hydrolytic activity toward
      cotton is partially damaged by the cationisation. The reason can be attributed to
      the movement restriction and dysfunction of cellulase protein by the
      cationisation. 

PMID- 24750621
TI  - Ultrasonic-assisted extraction, antimicrobial and antioxidant activities of
      Cyclocarya paliurus (Batal.) Iljinskaja polysaccharides.
AB  - Recently, renewed interest has grown in the use of ultrasonic-assisted extraction
      as an alternative approach to the traditional extraction methods. In this study,
      this novel extraction method was used to isolate polysaccharides from Cyclocarya
      paliurus (Batal.) Iljinskaja, and response surface methodology (RSM) was employed
      to optimize the extraction conditions. The optimal conditions for the extraction
      of polysaccharides were determined to be the ratio of liquid to solid of 8,
      extraction time of 59 min and extraction temperature of 58  degrees C. Under
      these optimal conditions, the yield of polysaccharides obtained was 4.91 +/-
      0.11%, which was well matched with the value predicted by the model. In vitro
      antioxidant assays showed that the polysaccharides exhibited strong DPPH radicals
      (92.09% at 0.25 mg/ml) and self-oxidation of 1,2,3-phentriol (37.22% at 1 mg/ml)
      scavenging activities, moderate hydroxyl radicals (43.18% at 1 mg/ml) scavenging
      activity and lipid peroxidation inhibitory effect (31.66% at 1 mg/ml). In
      addition, the polysaccharides showed moderate antimicrobial activity.

PMID- 24750622
TI  - Modeling and mechanism of the adsorption of copper ion onto natural bamboo
      sawdust.
AB  - The sorption of copper ions onto natural bamboo sawdust with cellulose-lignin
      polymeric structure strongly depends on pH. The adsorption capacity for copper
      ions increases as increasing pH and copper loadings. The fitting of copper pH
      boundary curve by NEM surface complexation models shows that: three-sites model
      including the ion exchange reaction of permanent charge fits better than two
      sites model. The incorporation of the hydrated ion reaction gives better fitting
      results. XAFS study shows that: copper ions mainly form inner complexation with
      sawdust, but there is no obvious evidence on the complexation of carboxylic acid
      groups with copper ions. EXAFS fitting result shows that: as pH rises, the
      spatial configuration of copper ions shifts from tetrahedron to octahedron.
      Meanwhile the increase in the coordination number indicates that hydrated copper
      ions participate in the adsorption. Both XANES and EXFAS spectrum offer a similar
      explanation for copper adsorption in the range of experimental and fitting
      errors. 

PMID- 24750623
TI  - Synthesis and applications of vegetable oil-based fluorocarbon water repellent
      agents on cotton fabrics.
AB  - Vegetable oil-based fluorocarbon water repellent agents were prepared by chemical
      modifications of different vegetable oils - soybean and linseed oils through
      several reactions, including saponification, acidification, acylation of
      vegetable oil and trans-esterification with 2,2,2-trifluoroethanol and 2,2,3,3
      tetrafluoropropanol. The resulted fluorocarbon agents were then copolymerized
      with styrene. The structures of the vegetable oil based agents were characterized
      by FT-IR and NMR. By evaluating water contact angle and time of water
      disappearance on cotton fabrics, as well as whiteness and breaking strength of
      cotton fabrics that were treated by these agents, optimum fabric finishing
      conditions were explored. The cotton fabrics finished with the vegetable oil
      based fluorocarbon agents showed excellent water repellency, while other
      properties of the cotton fabrics declined to certain level. The linseed oil-based
      tetrafluoropropanol water repellent agent displayed the highest water repellency
      among all modified oils. All the treated fabrics exhibited good durability of
      water repellency. The linseed oil-based tetrafluoropropanol water repellent agent
      demonstrated the best durability among all repellent agents. 

PMID- 24750624
TI  - Effect of okra gum on the pasting, thermal, and viscous properties of rice and
      sorghum starches.
AB  - The effect of okra gum (OE) on the physical properties of rice and sorghum
      starches was investigated using rapid visco-analyzer (RVA), Brookfield
      viscometer, differential scanning Calorimetry (DSC), and light microscopy. Starch
      was replaced with 5, 10, 15% OE weight basis (g/100 g). In the presence of OE,
      the peak and final viscosity as well as the setback of both starches were
      reduced. However, the difference between the theoretical and the measured setback
      was more than just can be attributed to the omitted starch. The DSC data of the
      blends showed higher peak temperature compared to the control, indicating slower
      starch gelatinization in the presence of OE. Brookfield profiles demonstrated
      increase in shear stress at higher shear rate confirming pseudoplasticity of the
      system (n<1). Over all, it can be assumed that OE has influenced the properties
      of the starches, particularly, by decreasing viscosity, setback, and
      pseudoplasticity of the starch gels.

PMID- 24750625
TI  - Complexation of carbendazim with hydroxypropyl-beta-cyclodextrin to improve
      solubility and fungicidal activity.
AB  - The effect of hydroxypropyl-beta-cyclodextrin (HPbetaCD) on the improvement of
      the solubility and fungicidal activity of carbendazim (MBC) has been
      investigated. The inclusion complexation of HPbetaCD with MBC has been prepared
      and characterized by phase solubility diagram, fluorescence, (1)H NMR, ROESY and
      FT-IR spectra. The stoichiometric ratio and stability constant were determined by
      Job's plot and phase solubility studies, respectively. The inclusion complex
      MBC.HPbetaCD has exhibited different properties from MBC. The obtained inclusion
      complex was found to significantly improve the water solubility of MBC. In
      addition, the biological activity indicated that the complex displayed the better
      fungicidal activity than MBC. The present study provided useful information for a
      more rational application of MBC. 

PMID- 24750626
TI  - Analysis of crystallinity changes in cellulose II polymers using carbohydrate
      binding modules.
AB  - Carbohydrate-binding modules (CBMs) are a set of tools that can be used as
      molecular probes for studying plant cell walls and cellulose-based substrates.
      CBMs from enzymes of bacterial and fungal origin present a range of recognition
      capabilities for crystalline and amorphous cellulose. Here cellulose-directed
      CBMs have been used to visualize and quantify crystallinity changes in cellulose
      II-based polymers following NaOH treatment. Cellulose II polymers used were in
      the form of lyocell fibers, which are derived from eucalyptus wood pulp. The
      supramolecular structure, morphology, and existence of 'skin-core' model in the
      fiber were examined using CBM-labeling techniques. Changes in cellulose
      crystallinity showed maxima at 3.33 mol dm(-3) NaOH (under treatment conditions
      of 49 Nm(-1) at 25  degrees C) and 4.48 mol dm(-3) NaOH (under treatment
      conditions of 147 Nm(-1) at 40  degrees C); CBM methods were also suitable for
      quantifying changes within amorphous regions. Quantification of crystallinity
      changes using CBM labeling techniques was achieved in combination with image
      analysis, which was shown to reflect the same crystallinity changes as measured
      using ATR-FTIR methods. It was demonstrated that CBM-labeling techniques were
      able to validate the proposed 'skin-core' model of lyocell fibers, comprising a
      semi-permeable fiber skin and a porous core.

PMID- 24750627
TI  - A novel hybrid system for the fabrication of a fibrous mesh with micro
      inclusions.
AB  - A novel hybrid system combining microfluidic and co-axial electrospinning
      techniques has been used to generate different types of fibre structures with
      varied desirable inclusions using food grade polymers, ethyl cellulose and sodium
      alginate. The processing conditions in the microfluidic T-junction device, i.e.
      gas pressure and liquid flow rate were adjusted in order to generate near
      monodisperse microbubbles which subsequently serve as a platform for particle
      generation. These particles exhibit micro-scale diameters and different shapes
      and some bubbles were incorporated into the fibrous mesh prepared by concurrent
      electrospinning. The fibre/particle structures obtained with different polymers
      via this novel method could potentially have many applications in various
      engineering and biological sectors. 

PMID- 24750628
TI  - Effect of extraction time and temperature on the characteristics of loosely bound
      pectins from Japanese plum.
AB  - The cell wall composition of Japanese plums (Prunus salicina) at six
      developmental stages was previously evaluated (Ponce et al., J. Agric. Food Chem.
      2010, 58, 2562-2570). This fruit is an interesting source of pectins,
      polysaccharides of valuable functionality for pharmaceutical and food
      formulations. In the present work it was investigated how the different
      conditions for the aqueous extraction of pectins from Japanese plums affect the
      yield as well as their chemical and rheological characteristics. It has been
      determined that extraction with water at room temperature for periods longer than
      2h did not produce additional increment of yield (12%) but decreased the average
      molecular weights of the extracted pectins. Pectins with a degree of methylation
      ~40% with high viscosity in water and with adequate molecular weights (~72,000)
      were obtained. Conversely, utilization of boiling water for extraction increased
      considerably the yields (33-38%) but the extracted pectins showed significant
      lower viscosity in water in spite of their higher molecular weights. The poorer
      thickening ability was associated to the lower proportion of arabinose residues
      present in the hairy regions of the pectin macromolecules extracted by hot water,
      which led the polymers to interact more transiently in a 2% w/v water solution. 

PMID- 24750629
TI  - Preparation of silver nanoparticles in the presence of chitosan by
      electrochemical method.
AB  - The present study involves the development of stabilized and densely dispersed
      chitosan-silver nanoparticles using a green approach based on electrochemical
      oxidation/complexation process followed by UV irradiation reduction. Formation of
      the nanoparticles was confirmed by appearance of surface plasmon absorption
      around 420 nm. The nanoparticles were characterized using transmission electron
      microscopy, X-ray diffraction, elemental analysis, atomic absorption, energy
      dispersive X-ray, Fourier transform infrared, and UV-Visible spectrophotometry.
      The obtained nanoparticles were uniform and spherical with average size of 2-16
      nm. It was found that increasing the Ag content in the chitosan-Ag based films
      tends to decrease their equilibrium swelling values. The nanoparticles also
      demonstrated a relatively high antibacterial activity against Bacillus
      thuringiensis and Pseudomonas aeruginosa bacteria as compared to that of chitosan
      and the antibacterial activity increased with increasing the nanoparticle
      concentration. The obtained results revealed that the prepared nanoparticles
      could be tailored and used in various biomedical applications.

PMID- 24750630
TI  - Hypoglycemic and hypolipidemic activities of MT-alpha-glucan and its effect on
      immune function of diabetic mice.
AB  - The hypoglycemic and hypolipidemic effect of an alpha-glucan (designed here as MT
      alpha-glucan) from fruit body of maitake (Grifola frondosa) on diabetic mouse
      model induced by streptozotocin and high-fat-diet were evaluated, and its effect
      on immune function of diabetic mice was investigated. Treatment with MT-alpha
      glucan (300 or 100 mg kg(-1)) could decrease the levels of fasting plasma
      glucose, triglycerides, cholesterol, free fatty acid, the proliferative response
      of macrophages and IL-1, NO production by macrophages significantly. Treatment
      with MT-alpha-glucan could increase the serum insulin, the proliferative response
      and IL-2 production of splenocytes induced by ConA significantly. Ultrastructural
      changes of pancreatic beta-cells were ameliorated in the treatment group. These
      data suggest that MT-alpha-glucan has hypoglycemic and hypolipidemic effect on
      the diabetic mice model, which might be related to its benefit effect on immune
      reactions involved in pathogenesis of diabetes mellitus, leading to attenuate the
      degree of injured beta-cells of the pancreatic islets.

PMID- 24750631
TI  - Green natural rubber-g-modified starch for controlling urea release.
AB  - The hydrophilicity of natural rubber (NR) was improved by grafting with modified
      cassava starch (ST) (NR-g-ST) by using potassium persulfate (K2S2O8) as a
      catalyst. The modified ST was added to NR latex in the presence of Terric16A16 as
      a non-ionic surfactant at 60  degrees C for 3 h and cast film on a glass plate to
      obtain NR-g-ST. The chemical structure of NR-g-ST was confirmed by FTIR. The
      swelling ratio of NR-g-ST was investigated in water and results showed that the
      swelling ratio of the modified NR decreased as function of ST. In addition, the
      tensile strength of the modified NR in the presence of modified ST at 50 phr was
      the highest value. Also, the thermal stability modified NR-g-ST was higher than
      of NR/ST blend confirmed by TGA. Finally, the NR-g-ST was used a polymer membrane
      for controlling urea fertilizer and it easily degraded in soil. This product with
      good controlled-release and water-retention could be especially useful in
      agricultural and horticultural applications.

PMID- 24750632
TI  - Chemical and biological characterization of pectin-like polysaccharides from the
      bark of the Malian medicinal tree Cola cordifolia.
AB  - The bark of Cola cordifolia used in Malian traditional medicine contains unusual
      types of polysaccharides with immunomodulating activities. We report for the
      first time on the structure of a polymer designated CC1P1 having the repeating
      structure [2->)[alpha-D-Gal(1->3)]alpha-L-Rha(1->4)alpha-d-GalA(1->] as
      determined by NMR and GC/MS. alpha-Linked Gal is unusual in pectins. The Mw of
      135 kDa was determined by SEC-MALLS. CC1P2 (1400 kDa), another polymer, having
      the same backbone, but this was substituted with alpha-4-OMe-GlcA, alpha-2-OMe
      Gal and alpha-Gal as terminal units. CC1P1 shows a high complement-fixing
      activity, IC50 being 2.2 times lower than the positive pectin control PMII (IC50
      appr. 71 MUg/mL) while IC50 of CC1P2 is 1.8 times lower. The simple structure of
      CC1P1 did not activate macrophages, while CC1P2 (100 MUg/mL) showed the same
      potency as the positive controls PMII (100 MUg/mL) and LPS (500 ng/mL). No
      cytotoxicity was detected.

PMID- 24750633
TI  - Mechanical and antibacterial properties of recycled carton paper coated by PS/Ag
      nanocomposites for packaging.
AB  - Polymer nanocomposites and paper constitute a new class of packaging materials.
      In this study silver nanoparticles were prepared by novel method as antibacterial
      additive, where, synthetic takes place with aid of a novel, non-toxic, and eco
      friendly biological materials namely rice straw (RS) powder. The prepared Ag
      nanoparticle was examined by transmission electron microscope (TEM), X-ray
      diffraction pattern (XRD) and UV-spectroscopy. The silver nanoparticles were then
      embedded into commercial polystyrene solution. The recycled carton paper was
      coated by the polystyrene nanocomposites containing different concentration of
      silver nanoparticles, namely 2, 4, 6 and 8% based on polystyrene. The prepared
      recycled carton sheets were characterized by scanning electron microscope (SEM).
      The mechanical properties, water vapor permeability and antibacterial effect of
      recycled carton sheets were also investigated. 

PMID- 24750634
TI  - Microwave assisted synthesis of polyacrylamide grafted gum ghatti and its
      application as flocculant.
AB  - Polyacrylamide chains (PAM) were grafted onto the backbone of gum ghatti by
      microwave assisted method. The grafting of the PAM chains on the polysaccharide
      backbone was confirmed through intrinsic viscosity study, FTIR spectroscopy,
      elemental analysis (C, H & N) and SEM morphology study. The intrinsic viscosity
      of gum ghatti appreciably improved on grafting of PAM chains, thus resulting
      grafted product with potential application as superior viscosifier. Further,
      flocculation efficacy of the graft copolymer was studied initially in kaolin
      suspension and then in municipal wastewater through 'Jar test' procedure, toward
      possible application as flocculant for wastewater treatment. 

PMID- 24750635
TI  - Chitosan/carrageenan nanoparticles: effect of cross-linking with tripolyphosphate
      and charge ratios.
AB  - Chitosan/carrageenan/tripolyphosphate nanoparticles were prepared by
      polyelectrolyte complexation/ionic gelation, the latter compound acting as cross
      linker. The incorporation of the three components in the nanoparticle matrix was
      assessed by analytical techniques (FTIR, XPS and TOF-SIMS). Using
      chitosan/carrageenan nanoparticles as control, the effect of the cross-linker in
      the particles properties was studied. A decrease in size (from 450-500 nm to 150
      300 nm) and in zeta potential (from +75 - +85 mV to +50 - +60 mV), and an
      increase in production yield (from 15-20% to 25-35%), and in stability (from one
      week to up to 9 months) were observed. Also, a correlation between positive to
      negative charge ratios in the formulations and the above characteristics was
      established. The small size and high positive surface charge make the developed
      chitosan/carrageenan/tripolyphosphate nanoparticles potential tools for an
      application in mucosal delivery of macromolecules.

PMID- 24750636
TI  - Effect of crosslinker and nanoclay on starch and jute fabric based green
      nanocomposites.
AB  - 'Green' nanocomposites were prepared by solution induced intercalation method
      using starch, jute, glutaraldehyde, nanoclay and glycerol. The concentration of
      glycerol was optimised. The synthesized composites were characterized by various
      physicochemical and spectrochemical techniques such as Fourier transform infrared
      spectroscopy, X-ray diffractometry, transmission electron microscopy, scanning
      electron microscopy, and thermogravimetric analysis. Fourier transform infrared
      spectroscopy study indicated an interaction between the jute, starch and clay.
      Good adhesion exists between starch and jute surface as revealed by scanning
      electron microscope study. The extent of exfoliation of clay was studied by X-ray
      diffraction and transmission electron microscope studies. The addition of
      glutaraldehyde and nanoclay has been found to improve the thermal stability,
      flame retardancy, dimensional stability and mechanical strength of the prepared
      composite. 

PMID- 24750637
TI  - Direct hydrolysis of cellulose to glucose using ultra-high temperature and
      pressure steam explosion.
AB  - Hydrolysis of two cellulosic materials, i.e. microcrystalline cellulose powder
      (MC) and cuprammonium rayon fiber (BEMCOT), to glucose was carried out by steam
      explosion treatment with ultra-high temperature and pressure steam aiming at an
      effective usage of unutilized cellulosic materials. 50 g of cellulosic materials
      were charged in a sealed reactor (2L) of the steam explosion apparatus kept at
      steam pressures of 50, 55, 60, and 62 atm for a steaming time of 1 min. The
      maximum yield of water soluble sugars, 52.8%, was obtained at a steam pressure of
      62 atm and a steaming time of 1 min for MC. Furthermore, the maximum yield of
      water soluble sugars, 67.7%, was obtained at a steam pressure of 60 atm and a
      steaming time of 1 min for BEMCOT. This water soluble sugars contained 63.1% and
      61.0% of glucose, respectively; they are corresponding to 33.3g and 41.0 g of
      glucose contained in 100g of dry steam-exploded cellulosic material.

PMID- 24750638
TI  - Antioxidant and renoprotective activity of chitosan in nephrectomized rats.
AB  - The effect of chitosan on oxidative stress and chronic renal failure was
      investigated using 5/6 nephrectomized rats. The ingestion of chitosan over a 4
      week period resulted in a significant decrease in total body weight, glucose,
      serum creatinine and indoxyl sulfate levels (P=0.0011, P=0.0006, P=0.0012, and
      P=0.0005, respectively), compared with the non-treated nephrectomized group. The
      ingestion of chitosan also resulted in a lowered ratio of oxidized to reduced
      albumin (P=0.003) and an increase in biological antioxidant potential (P=0.023).
      Interestingly, the oxidized albumin ratio was correlated with serum indoxyl
      sulfate levels in vivo. These results suggest that the ingestion of chitosan
      results in a significant reduction in the levels of pro-oxidants, such as uremic
      toxins, in the gastrointestinal tract, thereby inhibiting the subsequent
      development of oxidative stress in the systemic circulation. 

PMID- 24750640
TI  - Measuring Outcomes: Pain and Quality of Life 48 Months After Acute Postoperative
      Total Knee Prosthetic Joint Infection.
AB  - BACKGROUND: Measuring HRQOL is simple, inexpensive, permits the health status to
      be measured over time, and is useful to compare or initiate treatments and
      evaluate results, facilitating homogenization in patient inclusion. OBJECTIVES:
      To evaluate disease-specific and generic HRQOL and influence of associated
      factors in patients undergoing open debridement for acute postsurgical knee
      prosthetic joint infection after TKR at 12 and 48 months after completing
      antibiotic treatment and considered cured of infection. METHODS: Health-related
      quality-of-life measures were administered at baseline (WOMAC) and 12 and 48
      months (WOMAC and SF-36) in patients with prosthesis retention, no symptoms of
      infection, and CRP (<= 1 mg/dL). RESULTS: Thirty patients were included, and 24
      were evaluated at 48 months. WOMAC scores improved significantly (P < 0.01) at 12
      and 48 months. The effect size was 0.72 for stiffness, 2.01 for pain, and 2.15
      for function. At 48 months, improvements were greater (P < 0.02) except for
      stiffness. The most frequently isolated microorganisms were Staphylococcus aureus
      (14 patients) and coagulase-negative staphylococci (9 patients). SF-36 physical
      role, bodily pain, emotional role, and mental health dimension scores at 12 and
      48 months were significantly worse in patients with isolates of Staphylococcus
      aureus (P < 0.05). CONCLUSIONS: Health-related quality-of-life measures detected
      significant differences in outcomes in patients infected by S. aureus compared
      with patients infected by other microorganisms. HRQOL measures may provide useful
      complementary information on outcomes after acute postoperative infection.

PMID- 24750642
TI  - The burden of alcoholism in fifteen years of cirrhosis hospital admissions in
      Portugal.
AB  - BACKGROUND & AIMS: Deploying a longitudinal perspective, we observe how cirrhosis
      caused mortality rates in Portugal are converging with the levels reported in the
      European Union (15 countries). However, we still lack analysis of the burden of
      alcoholic cirrhosis in terms of hospital admissions and associated mortality. As
      Portugal may be considered a paradigmatic case in Europe, our aim was to
      characterize the evolution of hospital admissions for alcoholic cirrhosis between
      1993 and 2008 and draw conclusions for other countries. METHODS: Retrospective
      analysis of the hepatic cirrhosis admissions in 97 Portuguese state hospitals was
      carried out based on the National Registry. RESULTS: We report a convergence in
      terms of mortality rates resulting from cirrhosis between Portugal and European
      Union (a differential of 6.7 deaths per 100 000 habitants in 1994 to 0.4 in
      2008). We accounted for 81 543 hospital admissions for cirrhosis: 84% for
      alcoholic cirrhosis and 16% for non-alcoholic cirrhosis. Hospital admissions have
      increased 29% in men and with no increase in women. In the male, alcoholic
      cirrhosis patient group aged between 40 and 54, the rise in hospital admissions
      was more pronounced with an increase of around 45%. These patients underwent
      longer lengths of stay and reported higher mortality rates and passing away 20
      years earlier than the average national expectancy of life. CONCLUSIONS: These
      data draw attention to the burden of alcohol consumption not only in Portugal but
      also in other countries and its impacts on hospital systems and on policy making.

PMID- 24750641
TI  - Ecotoxicological effects of carbon nanotubes and cellulose nanofibers in
      Chlorella vulgaris.
AB  - BACKGROUND: MWCNT and CNF are interesting NPs that possess great potential for
      applications in various fields such as water treatment, reinforcement materials
      and medical devices. However, the rapid dissemination of NPs can impact the
      environment and in the human health. Thus, the aim of this study was to evaluate
      the MWCNT and cotton CNF toxicological effects on freshwater green microalgae
      Chlorella vulgaris. RESULTS: Exposure to MWCNT and cotton CNF led to reductions
      on algal growth and cell viability. NP exposure induced reactive oxygen species
      (ROS) production and a decreased of intracellular ATP levels. Addition of NPs
      further induced ultrastructural cell damage. MWCNTs penetrate the cell membrane
      and individual MWCNTs are seen in the cytoplasm while no evidence of cotton CNFs
      was found inside the cells. Cellular uptake of MWCNT was observed in algae cells
      cultured in BB medium, but cells cultured in Seine river water did not
      internalize MWCNTs. CONCLUSIONS: Under the conditions tested, such results
      confirmed that exposure to MWCNTs and to cotton CNFs affects cell viability and
      algal growth.

PMID- 24750643
TI  - Premenstrual syndrome and dysmenorrhea: symptom trajectories over 13 years in
      young adults.
AB  - OBJECTIVES: To ascertain the prevalence of premenstrual syndrome (PMS) and
      dysmenorrhea in Australia women and to examine whether there is population
      subgroups with distinct symptom trajectories. STUDY DESIGN: A prospective cohort
      study, including 9671 young women random sampled from national Medicare database
      and followed up for 13 years, examined the prevalence, the trend and the symptom
      trajectories of the conditions. MAIN OUTCOME MEASURES: Prevalence of PMS and
      dysmenorrhea over time, their symptom trajectories, and the probability of
      symptom reporting at follow-up. RESULTS: The prevalence of PMS varied between 33
      and 41% and that of dysmenorrhea between 21 and 26%. The probabilities of
      reporting PMS and dysmenorrhea were 0.75 (95% CI, 0.73, 0.76) and 0.70 (95% CI,
      0.68, 0.72), respectively, among women who reported them in three previous
      consecutive surveys. Four unique trajectories were identified for both
      conditions. PMS was experienced by 80% of women some time during the study
      period, with normative (22.1%), late onset (21.9%), recovering (26.5%) and
      chronic (29.5%) groups revealed. Dysmenorrhea occurred in 60% of women with
      normative (38.3%), low (28.0%), recovering (17.2%) and chronic (16.5%) groups
      identified. CONCLUSIONS: PMS and dysmenorrhea are common among young women. Both
      have relatively stable prevalence over time, but exhibit considerable variation
      at the individual level. Four subgroups of women who followed similar symptom
      trajectories were identified. PMS was experienced by 80% of women during the
      study period and it tended to be a long-lasting problem in many. Although 60% of
      women experienced dysmenorrhea, only a small group continuously reported it.
      Smoking and illicit drugs use, and smoking and obesity were more common among
      women with persistent PMS and dysmenorrhea respectively.

PMID- 24750644
TI  - Dipeptidyl peptidase-4 inhibitors and cardiovascular outcomes: meta-analysis of
      randomized clinical trials with 55,141 participants.
AB  - AIMS: The association between glucose lowering in diabetes mellitus and major
      cardiovascular (CV) outcomes is weak; indeed, some oral hypoglycemic agents are
      associated with increased CV events. Dipeptidyl peptidase-4 inhibitors (DPP-4
      inhibitors) are a new class of oral hypoglycemic agent that may have beneficial
      CV effects. We undertook a systematic review and meta-analysis to appraise the CV
      safety and efficacy of DPP-4 inhibitors. METHODS: Comprehensive search for
      prospective trials involving DPP-4 inhibitors. Trials included reported at least
      one of the outcomes examined, recruited minimum 100 patients and minimum follow
      up 24 weeks. The risk ratio (RR) was calculated using the Mantel-Haenszel random
      effects model for mortality and major cardiovascular (CV) outcomes. RESULTS:
      Fifty trials enrolling 55,141 participants were included. Mean follow-up 45.3
      weeks. DPP-4 inhibitors compared with all comparators (placebo and active) showed
      no difference in all-cause mortality (n = 50,982, RR = 1.01, 95% CI 0.91-1.13, P
      = 0.83), CV mortality (n = 48,151, RR = 0.97, 95% CI 0.85-1.11, P = 0.70), acute
      coronary syndrome (ACS) (n = 53,034 RR = 0.97, 95% CI 0.87-1.08, P = 0.59), or
      stroke (n = 42,737, RR = 0.98, 95% CI 0.81-1.18, P = 0.80), and a statistically
      significant increase in heart failure outcomes (n = 39,953, RR = 1.16, 95% CI
      1.01-1.33, P = 0.04). DISCUSSION: Treatment with DPP-4 inhibitors compared with
      placebo shows no increase in risk with regards to all-cause mortality, CV
      mortality, ACS, or stroke, but a statistically significant trend toward increased
      risk of HF outcomes. CONCLUSION: These findings suggest no cardiovascular harm
      (or benefit) with DPP-4 inhibitors; further large-scale CV outcome studies will
      resolve the issue of excess HF risk.

PMID- 24750645
TI  - Biological relevance of CNV calling methods using familial relatedness including
      monozygotic twins.
AB  - BACKGROUND: Studies involving the analysis of structural variation including Copy
      Number Variation (CNV) have recently exploded in the literature. Furthermore,
      CNVs have been associated with a number of complex diseases and
      neurodevelopmental disorders. Common methods for CNV detection use SNP, CNV, or
      CGH arrays, where the signal intensities of consecutive probes are used to define
      the number of copies associated with a given genomic region. These practices pose
      a number of challenges that interfere with the ability of available methods to
      accurately call CNVs. It has, therefore, become necessary to develop experimental
      protocols to test the reliability of CNV calling methods from microarray data so
      that researchers can properly discriminate biologically relevant data from noise.
      RESULTS: We have developed a workflow for the integration of data from multiple
      CNV calling algorithms using the same array results. It uses four CNV calling
      programs: PennCNV (PC), Affymetrix(r) Genotyping ConsoleTM (AGC), Partek(r)
      Genomics SuiteTM (PGS) and Golden Helix SVSTM (GH) to analyze CEL files from the
      Affymetrix(r) Human SNP 6.0 ArrayTM. To assess the relative suitability of each
      program, we used individuals of known genetic relationships. We found significant
      differences in CNV calls obtained by different CNV calling programs. CONCLUSIONS:
      Although the programs showed variable patterns of CNVs in the same individuals,
      their distribution in individuals of different degrees of genetic relatedness has
      allowed us to offer two suggestions. The first involves the use of multiple
      algorithms for the detection of the largest possible number of CNVs, and the
      second suggests the use of PennCNV over all other methods when the use of only
      one software program is desirable.

PMID- 24750646
TI  - Nature versus nurture.

PMID- 24750647
TI  - Enriching a classroom lesson on grief and loss.

PMID- 24750648
TI  - Lean in to our profession.
AB  - Nurses play a critical role in the delivery of high-quality, evidence-based
      health care. Nurses can "lean in" to our professional by voicing our opinions,
      contributing to decisions affecting health care practice and policy, and assuming
      leadership roles. 

PMID- 24750650
TI  - Donor motivations, associated risks and ethical considerations of oocyte
      donation.
AB  - Three decades after the first reported successful cases, oocyte donation
      continues to grow in popularity and regard as an established method to aid women
      in achieving their reproductive goals. As a result of the increased demand for
      donated oocytes, many young women in the U.S. volunteer to undergo complex
      medical procedures to donate their oocytes in return for financial compensation.
      To best care for these women before, during and after donation, it is important
      to explore donor characteristics and motivations, discuss the safety of the
      donation procedure and examine the ethical issues related to this process. 

PMID- 24750651
TI  - Ankyloglossia its impact breastfeeding.
AB  - This article contrasts two very different experiences of one mother breastfeeding
      her two sons to demonstrate the potential impact of ankyloglossia on
      breastfeeding. When too restrictive, ankyloglossia, also known as tongue-tie, can
      cause the newborn to ineffectively suckle at the breast. Breastfeeding
      difficulties can occur, such as long feedings or damaged nipples. When nurses,
      lactation consultants and other providers recognize this situation, they can
      refer women for further care and treatment, which can ultimately lead to
      breastfeeding success. 

PMID- 24750652
TI  - Planning a collaborative conference to provide interdisciplinary education with a
      focus on patient safety in obstetrics.
AB  - Collaboration is an important component of evidence-based practice in modern
      health care. A number of publications have touted the benefits of "team training"
      to improve obstetric outcomes during emergent situations. In August 2011, the
      Ohio sections of the Association of Women's Health, Obstetric and Neonatal Nurses
      (AWHONN) and the American Congress of Obstetricians and Gynecologists (ACOG) held
      a joint conference that focused on interdisciplinary education to promote patient
      safety. This joint venture drew more than 120 attendees, 12 exhibitors and 17
      poster displays. Evaluations were positive and attendees cited planned practice
      changes for themselves as well as for their respective institutions. 

PMID- 24750654
TI  - The increasing role of genetics and genomics in women's health.
AB  - Genetic and genomic testing are a clinical reality in health care today. Persons
      at risk for disease or who are simply curious about their genomes can have them
      analyzed. An individual's genome is a function of ancestry, family history and
      personal health and environmental exposures. Clinical and pharmacologic
      information can be obtained through genomic analysis. Genomic testing can be done
      by health care providers but some results can now be obtained through direct-to
      consumer tests. Many ethical questions are being raised regarding genomic
      testing. Nurses can provide more optimal care by understanding the process of
      genomic testing as well as the implications of the results. 

PMID- 24750653
TI  - Fertility preservation options for women treated for cancer.
AB  - Cancer treatments, including chemotherapy, radiotherapy and surgery can be
      damaging to reproductive organs and can decrease fertility in women of
      reproductive age. For women who may wish to try to preserve their fertility, it's
      important for clinicians to discuss potential options with women before the
      initiation of cancer treatment to maintain as many preservation options as
      possible. Embryo cryopreservation, oocyte cryopreservation and ovarian tissue
      cryopreservation are potential options, but most of these methods are still
      considered experimental and may not be an option for every woman. 

PMID- 24750655
TI  - Health implications of human trafficking.
AB  - Freedom is arguably the most cherished right in the United States. But each year,
      approximately 14,500 to 17,500 women, men and children are trafficked into the
      United States for the purposes of forced labor or sexual exploitation. Human
      trafficking has significant effects on both physical and mental health. This
      article describes the features of human trafficking, its physical and mental
      health effects and the vital role nurses can play in providing care to this
      vulnerable population. 

PMID- 24750656
TI  - Making connections to develop a professional network.
AB  - Developing a professional network is important for career growth and professional
      development. Networking can open doors for countless opportunities to gain new
      knowledge, meet new people, visit new places and advance your career. Successful
      networking involves identifying opportunities to meet and interact with people
      and to do so in a genuine way that fosters the development of a professional
      relationship. 

PMID- 24750657
TI  - Defining severe maternal morbidity.

PMID- 24750659
TI  - Infertility treatment as a covered health insurance benefit.

PMID- 24750660
TI  - A Midwife's Gratitude.

PMID- 24750661
TI  - Poor agreement between transcranial Doppler and near-infrared spectroscopy-based
      estimates of cerebral blood flow changes in sepsis.
AB  - BACKGROUND: Continuous monitoring of cerebral blood flow (CBF) may be valuable in
      critically ill patients with sepsis. In this study, we compared spatially
      resolved near-infrared spectroscopy (NIRS) to transcranial Doppler ultrasound
      (TCD)-derived estimates of noradrenaline-associated changes in CBF in such
      patients. METHODS: Mean arterial blood pressure (MAP) was elevated by increasing
      the noradrenaline infusion rate in eight mechanically ventilated, critically ill
      patients diagnosed with severe sepsis or septic shock. The associated changes in
      CBF were assessed by simultaneous ipsilateral NIRS (ScO(2)) and TCD (middle
      cerebral artery blood flow velocity, MCAv) measurements. RESULTS: A total of
      fifteen simultaneous NIRS- and TCD-derived assessments of noradrenaline
      associated changes in CBF were obtained. MAP was increased from 74 (median;
      interquartile range (IQR), 71-90) to 100 (median; IQR, 93-115) mmHg (P<0.05),
      which was associated with an increase in MCAv of 14% (median; IQR, 2-22; P<0.05),
      whereas no changes were observed in ScO(2) ; 1% (median; IQR, [-4]-3; P = 0.96).
      A Bland-Altman plot was used to compare the two methods and showed a poor
      agreement between NIRS- and TCD-derived estimates with a relative bias of 14% and
      limits of agreement of -18% to 45% change in CBF. CONCLUSION: Our findings stress
      that TCD and NIRS cannot be used interchangeably for monitoring changes in
      cerebral haemodynamics in critically ill patients with sepsis receiving
      vasopressor treatment with noradrenaline.

PMID- 24750662
TI  - High Prevalence of Neuropathic Pain Features in Patients with Knee
      Osteoarthritis: A Cross-Sectional Study.
AB  - OBJECTIVE: The present epidemiological research evaluated the prevalence of
      neuropathic pain characteristics in patients with painful knee osteoarthritis
      (OA) and the plausibility that such neuropathic features were specific of OA.
      METHODS: Outpatients with chronic pain associated with knee OA who attended
      orthopedic surgery or rehabilitation clinics were systematically screened for
      neuropathic pain with the Douleur Neuropathique in 4 questions (DN4)
      questionnaire. Data from medical files and those obtained during a single
      structured clinical interview were correlated with the DN4 scores. Information on
      potential confounders of neuropathic-like qualities of knee pain was collected to
      evaluate as much as possible only the symptoms attributable to OA. RESULTS: Of
      2,776 patients recruited, 2,167 patients provided valid data from 2,992 knees.
      The DN4 was scored positively (>= 4) in 1,125 patients (51.9%) and 1,459 knees
      (48.8%). When patients with potential confounders were excluded, the respective
      prevalences were 33.3% and 29.4%. Patients who scored positively in the DN4 had
      more severe pain, greater structural damage, and more potential confounders of
      neuropathic pain. Three potential confounders conveyed much of the variability
      explained by regression analyses. However, latent class analyses revealed that
      the concourse of other factors is required to explain the neuropathic pain
      qualities. CONCLUSIONS: A relevant proportion of patients with chronic pain
      associated with knee OA featured neuropathic pain qualities that were not
      explained by other conditions. The present research has provided reasonable
      epidemiological grounds to attempt their definite diagnosis and classification.

PMID- 24750663
TI  - Human infections with Rickettsia raoultii, China.
AB  - We used molecular methods to identify Rickettsia raoultii infections in 2 persons
      in China. These persons had localized rashes around sites of tick bites. R.
      raoultii DNA was detected in 4% of Dermacentor silvarum ticks collected in the
      same area of China and in 1 feeding tick detached from 1 patient. 

PMID- 24750664
TI  - The pan-caspase inhibitor Emricasan (IDN-6556) decreases liver injury and
      fibrosis in a murine model of non-alcoholic steatohepatitis.
AB  - BACKGROUND & AIMS: Hepatocyte apoptosis, the hallmark of non-alcoholic
      steatohepatitis (NASH) contributes to liver injury and fibrosis. Although, both
      the intrinsic and extrinsic apoptotic pathways are involved in the pathogenesis
      of NASH, the final common step of apoptosis is executed by a family of cysteine
      proteases termed caspases. Thus, our aim was to ascertain if administration of
      Emricasan, a pan-caspase inhibitor, ameliorates liver injury and fibrosis in a
      murine model of NASH. METHODS: C57/BL6J-mice were fed regular chow or high fat
      diet (HFD) for 20 weeks. All mice were treated with vehicle or Emricasan.
      RESULTS: Mice fed a HFD diet demonstrate a five-fold increase in hepatocyte
      apoptosis by the TUNEL assay and a 1.5-fold and 1.3-fold increase in caspase-3
      and-8 activities respectively; this increase in apoptosis was substantially
      attenuated in mice fed a HFD treated with Emricasan (HFD-Em). Likewise, liver
      injury and inflammation were reduced in mice fed HFD-Em as compare to HFD by
      measuring serum aspartate aminotransferase and alanine aminotransferase levels,
      NAS histological score and IL 1-beta, TNF-alpha, monocyte chemoattractant protein
      (MCP-1) and C-X-C chemokine ligand-2 (CXCL2) quantitative reverse-transcription
      polymerase chain reaction (qPCR). These differences could not be attributed to
      differences in hepatic steatosis as liver triglycerides content were similar in
      both HFD groups. Hepatic fibrosis was reduced by Emricasan in HFD animals by
      decreasing alphaSMA (a marker for hepatic stellate cell activation), fibrosis
      score, Sirius red staining, hydroxyproline liver content and profibrogenic
      cytokines by qPCR. CONCLUSION: In conclusion, these data demonstrate that in a
      murine model of NASH, liver injury and fibrosis are suppressed by inhibiting
      hepatocytes apoptosis and suggests that Emricasan may be an attractive
      antifibrotic therapy in NASH.

PMID- 24750665
TI  - Late-developing tongue adenoid cystic carcinoma after pulmonary metastasectomy: a
      case report.
AB  - Adenoid cystic carcinoma (ACC) is a relatively rare epithelial tumor of the
      salivary glands that accounts for approximately 5 to 10% of all salivary gland
      neoplasms. The typical clinical and pathological findings of this tumor include
      slow indolent growth, common local recurrence, and late distant metastasis to
      lung, brain, bone, liver, thyroid, and spleen. We report a 52-year-old female
      patient who presented a tongue ACC, 27 months after successful pulmonary ACC
      resection. 

PMID- 24750666
TI  - Regional variation in use of complementary health approaches by U.S. adults.
AB  - KEY FINDINGS: Data from the National Health Interview Survey, 2012 Use of
      nonvitamin, nonmineral dietary supplements (17.9%) was greater than any other
      complementary health approach used by U.S. adults in 2012. The use of
      practitioner-based chiropractic or osteopathic manipulation was nearly twice as
      high in the West North Central region as in the United States overall. Use of
      nonvitamin, nonmineral dietary supplements was highest in the Mountain, Pacific,
      and West North Central regions. Use of yoga with deep breathing or meditation was
      approximately 40% higher in the Pacific and Mountain regions than in the United
      States overall. Complementary health approaches are defined as "a group of
      diverse medical and health care interventions, practices, products, or
      disciplines that are not generally considered part of conventional medicine".
      They range from practitioner-based approaches, such as chiropractic manipulation
      and massage therapy, to predominantly self-care approaches, such as nonvitamin,
      nonmineral dietary supplements, meditation, and yoga. This report presents
      estimates of the four most commonly used complementary health approaches among
      adults aged 18 and over in nine geographic regions, using data from the 2012
      National Health Interview Survey adult alternative medicine supplement.

PMID- 24750667
TI  - Welcome to this issue of the International Journal of Laboratory Hematology.
      Introduction.

PMID- 24750668
TI  - Diagnosis and treatment of disseminated intravascular coagulation.
AB  - Disseminated intravascular coagulation (DIC) is a condition in which systemic
      activation of coagulation without a specific localization occurs, resulting in
      extensive formation of intravascular fibrin, particularly in small and midsize
      vessels. Disseminated intravascular coagulation may lead to several altered
      coagulation parameters, including a low platelet count, abnormal global clotting
      assays, low levels of physiological anticoagulant proteases, or increased fibrin
      degradation products. Also, more complex assays for activation of coagulation
      factors or pathways may indicate involvement of these molecules in DIC. None of
      these tests alone, however, can accurately ascertain or rebuff a diagnosis of
      DIC. Nonetheless, a combination of readily available routine assays may be
      instrumental in establishing a diagnosis of DIC and can also be useful to point
      to a subset of patients with DIC that may need definite, often costly,
      interventions in the hemostatic system. Current insights on relevant etiological
      pathways that may contribute to the occurrence of DIC have led to innovative
      therapeutic and adjunctive approaches to patient with DIC. Management options
      directed at the amelioration of hemostatic activation may tentatively be
      indicated and were found to be advantageous in experimental and clinical
      investigations. These treatments encompass elimination of tissue factor-mediated
      thrombin generation or restitution of normal anticoagulant function. 

PMID- 24750669
TI  - Red blood cell: from its mechanics to its motion in shear flow.
AB  - There is a number of publications on red blood cell deformability, that is, on
      the remarkable cell ability to change its shape in response to an external force
      and to pass through the narrowest blood capillaries and splenic sinuses. Cell
      deformability is postulated to be a major determinant of impaired perfusion,
      increase of blood viscosity, and occlusion in microvessels. Current deformability
      tests like ektacytometry measure global parameters, related to shape changes at
      the whole cell scale. Despite strong advances in our understanding of the
      molecular organization of red blood cells, the relationships between the rheology
      of each element of the cell composite structure, the global deformability tests,
      and the cell behavior in microflows are still not elucidated. This review
      describes recent advances in the description of the dynamics of red blood cells
      in shear flow and in the mechanistic understanding of this dynamics at the scale
      of the constitutive rheological and structural elements of the cell. These
      developments could open up new horizons for the determination of red blood cell
      mechanical parameters by analyzing their motion under low shear flows. 

PMID- 24750670
TI  - Toward routine detection of extracellular vesicles in clinical samples.
AB  - The majority, if not all, of human cell types secrete extracellular vesicles
      (EVs) into their environment, at least partly as a means of intercellular
      communication. These secreted vesicles can be detected in most bodily fluids
      including blood, urine, and saliva. The number of secreted vesicles and their
      composition is altered in various pathological conditions, raising opportunities
      to exploit EVs as diagnostic and/or prognostic biomarkers. For this to become a
      reality, it is important to reach consensus regarding the standardization of
      protocols for sample collection, EV isolation, handling, and storage for valid
      comparison and interpretation of measurements. Depending on the information
      required, there are several detection options including EV number and size
      distribution, molecular surface markers, procoagulation activity, and RNA
      content. For these purposes, different techniques are currently utilized or under
      development. This review discusses the techniques that have the potential to
      become standard EV detection methods in a clinical diagnostic setting. In
      addition to the accuracy of the detection technique, other factors such as high
      throughput, cost-effectiveness, time consumption, and required operator skill are
      important to consider. A combination of increasing fundamental knowledge,
      technological progress, standardization of sample collection, and processing
      protocols is required for EVs to become reliable predictors of altered physiology
      or development of disease suitable for routine clinical diagnostics. Cancer and
      (cardio)vascular disorders are examples of pathologies where EV detection may be
      applied in the near future for diagnosis and/or prognosis. 

PMID- 24750671
TI  - Flow cytometric pattern recognition of lymph node biopsies with lymphomas that
      lack lineage characteristics.
AB  - Although immunophenotyping (IPT) using flow cytometry is a routine technique that
      is applied in many laboratories as a diagnostic tool for lymphadenopathy, some
      diagnostic challenges persist. In this review, we will discuss pitfalls in the
      daily practice of lymph node diagnostics with the focus on general
      characteristics as lymphoid scatter patterns and lineage specific antigens that
      are used to define lymphoid populations. The absence of these characteristics on
      proliferating lymphoid cells can potentially lead to a wrong diagnosis. At the
      same time, this provides evidence for malignant transformation. Sporadic examples
      of reactive lymphoid proliferations with similar phenotypes are also discussed,
      illustrating the need for correlating IPT with morphology and clinical features. 

PMID- 24750672
TI  - Interpretation of coagulation test results under direct oral anticoagulants.
AB  - Diagnostic of global coagulation parameters is part of the daily clinical routine
      practice in conservative as well in operative disciplines. The correct
      interpretation of in vitro test results in context to the ex vivo influence of
      anticoagulant drugs and the in vivo hemostatic system of the individual patient
      is dependent on the doctors clinical and laboratory experience. This article
      shortly reviews the laboratory interference of oral anticoagulants including the
      target-specific inhibitors dabigatran, rivaroxaban and apixaban on coagulation
      parameters and discusses the potential of several methods for measuring the
      anticoagulant effect of the direct oral anticoagulants. 

PMID- 24750673
TI  - Thrombocytopenia: an update.
AB  - Thrombocytopenia is a common clinical problem with numerous potential causes
      including decreased bone marrow platelet production, increased peripheral
      platelet destruction, increased splenic sequestration, and dilution.
      Investigation of the etiology of thrombocytopenia requires careful consideration
      of clinical history and laboratory features. A complete blood count and
      peripheral smear review are essential components of the diagnostic work-up, and
      physicians should be knowledgeable about appropriate selection and interpretation
      of more specialized tests, including bone marrow examination, to assist with
      diagnosis. This review article aims to summarize and address appropriate work-up
      of the major and/or life-threatening causes of thrombocytopenia and some of the
      better-characterized congenital thrombocytopenias. 

PMID- 24750674
TI  - Leukocytosis.
AB  - An increased white blood cell count, or leukocytosis, is a common laboratory
      finding. Appropriate specimen evaluation depends on which lineages are increased
      and the morphologic findings on peripheral blood smear review to guide further
      testing. The presence of blasts is concerning for acute leukemia and may require
      bone marrow biopsy. Lymphocytosis may be morphologically divided into polymorphic
      and monomorphic populations. Polymorphic lymphocytosis is most consistent with a
      reactive process, while monomorphic populations are concerning for
      lymphoproliferative neoplasm. The differential can be further narrowed based on
      morphologic findings. Myeloid leukocytosis can occur in a number of reactive
      conditions as well as myeloid malignancies. The types of cells present and
      morphology can help to guide additional workup. This study provides guidance for
      the appropriate evaluation and further workup of leukocytosis. 

PMID- 24750675
TI  - Laboratory testing issues for protein C, protein S, and antithrombin.
AB  - Thrombophilia is a complex disease process, which clinically expresses as venous
      thrombosis. The presence of a genetic defect in one of the major contributing
      components (protein C [PC], protein S [PS], and antithrombin [AT]) to
      thrombophilia can be determined by clinical laboratory assays. However,
      understanding the limitations and problems associated with assays is paramount to
      an accurate analysis of the genetic status. This review will discuss the major
      analytical issues and provide recommendations for assaying PC, PS, and AT in
      plasma. Recommendations are also made about pre-analytical and postanalytical
      issues clinically affecting these assays. 

PMID- 24750676
TI  - Current insights into the laboratory diagnosis of HIT.
AB  - Heparin-induced thrombocytopenia (HIT) is an adverse drug reaction and
      prothrombotic disorder caused by immunization against platelet factor 4 (PF4)
      after complex formation with heparin or other polyanions. After antibody binding
      to PF4/heparin complexes, HIT antibodies are capable of intravascular platelet
      activation by cross-linking Fc gamma receptor IIa (FcgammaRIIa) on the platelet
      surface leading to a platelet count decrease and/or thrombosis. In contrast to
      most other immune-mediated disorders, the currently available laboratory tests
      for anti-PF4/heparin antibodies show a high sensitivity also for clinically
      irrelevant antibodies. This makes the diagnosis of HIT challenging and bears the
      risk to substantially overdiagnose HIT. The strength of the antigen assays for
      HIT is in ruling out HIT when the test is negative. Functional assays have a
      higher specificity for clinically relevant antibodies, but they are restricted to
      specialized laboratories. Currently, a Bayesian approach combining the clinical
      likelihood estimation for HIT with laboratory tests is the most appropriate
      approach to diagnose HIT. In this review, we give an overview on currently
      available diagnostic procedures and discuss their limitations. 

PMID- 24750677
TI  - ICSH: on board for new projects.
AB  - The International Council for Standardization in Hematology (ICSH) is a not-for
      profit organization aimed at improving global quality and harmonization of
      analytical methods, and achieving reliable and reproducible results in diagnostic
      hematology. ICSH co-ordinates Working Groups of experts to examine laboratory
      methods and instruments for hematological analyses, and co-operates with
      different international organizations which have similar scientific goals. Among
      seven ongoing approved projects, three ICSH projects have been selected and will
      be presented in the ICSH session at the XXVIIth ISLH International Symposium on
      Technological Innovations in Laboratory Hematology in The Hague, on May 2014. The
      project on 'Guideline for flow cytometric evaluation of patients with suspected
      acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS)' covers
      different aspects of the application of immunophenotyping by multiparameter flow
      cytometry (MFC) in the diagnosis of AML and MDS including integration into
      multimodal diagnostic workflow, quality control, antibody selection,
      interpretation of findings, reporting, and personnel. Data from the pilot study
      of the project for 'International Standardization of Hematology Reporting Units'
      suggest that there is a wide variation in reporting units for the routine blood
      cell count and highlights the areas of nomenclature and units of measurement
      where standardization is necessary and feasible, such as units for cell counts,
      white cell differentials, and hemoglobin concentration. The project on
      'Standardization of HbA2 measurement and its implications for clinical practice'
      starts from the observation that different instruments give different results for
      hemoglobin A2; it is aimed at producing recommendations as to how instrument
      manufacturers and laboratories should assess their equipment before using it to
      analyze patient samples. These projects are examples of how the ICSH represents a
      great opportunity for scientists involved in hematology laboratory to participate
      in a process of expert collaboration and discussion all around the world. 

PMID- 24750678
TI  - Update on the causes of platelet disorders and functional consequences.
AB  - Platelets are derived from megakaryocytes in the bone marrow that create the
      cellular machinery the platelet needs to participate in the different processes
      of primary hemostasis including adhesion, activation and clot formation at the
      site of injury. Defects related to megakaryocyte differentiation, platelet
      formation, and/or platelet function can result in bleeding. Patients with
      thrombopathies can present with mucous membrane bleeding but may also present
      with bleeding following trauma or surgery. In this review, we have classified
      inherited platelet bleeding disorders (IPD) according to their underlying
      defective pathway: transcription regulation, TPO signaling, cytoskeletal
      organization, apoptosis, granule trafficking, and receptor signaling. Platelet
      function testing has provided insights into the underlying molecular defects that
      can result in bleeding. A major step forward was made during the last 3 years
      using new-generation genetic approaches that resulted in the discovery of novel
      genes such as NBEAL2, RBM8A, ACTN1, and GFI1B for the well-known IPD that cause
      gray platelet syndrome, thrombocytopenia-absent radius syndrome, and autosomal
      dominant thrombocytopenias, respectively. In the near future, it is expected that
      a similar approach will identify many novel genes that cause IPD of unknown
      etiology, which are common. The future challenge will be to use a functional,
      systems biology approach to study the genes mutated in IPD and determine their
      roles in megakaryocyte and platelet biology and pathology.

PMID- 24750679
TI  - How should we test for nonsevere heritable platelet function disorders?
AB  - Heritable platelet function disorders (HPFD) are a heterogeneous group of
      bleeding disorders with diverse clinical and laboratory characteristics. In
      contrast to the severe phenotype disorders, Glanzmann thrombasthenia and Bernard
      Soulier syndrome, most nonsevere HPFD are incompletely characterized. This is a
      consequence of the poor standardization of diagnostic tests and of the lack of
      consensus about diagnostic criteria for the different subgroups of nonsevere
      HPFD. Distinguishing patients who have a nonsevere HPFD from those who do not is
      an essential first step in diagnosis which may be aided by bleeding assessment
      tools and screening tests such as the Platelet Function Analyser-100. However,
      high diagnostic accuracy can only be achieved with both light transmission
      aggregation (LTA) and secretion tests, for which streamlined agonist panels may
      be of similar utility to extended panels. Standardization of the methodology of
      these tests and quality assurance are essential for robust diagnosis.
      Identification of which platelet pathway is defective in patients with nonsevere
      HPFD is also usually possible with LTA and secretion tests. This strategy also
      sometimes enables exact diagnosis by implicating a single candidate protein and
      gene. Next-generation sequencing may offer a rapid approach to diagnosis of
      nonsevere HPFD, although rigorous strategies must be adopted to distinguish
      causative gene defects from bystander variations. 

PMID- 24750680
TI  - Technological advances in diagnostic testing for von Willebrand disease: new
      approaches and challenges.
AB  - Diagnostic tests for von Willebrand disease (VWD) are important for the
      assessment of VWD, which is a commonly encountered bleeding disorder worldwide.
      Technical innovations have been applied to improve the precision and lower limit
      of detection of von Willebrand factor (VWF) assays, including the ristocetin
      cofactor activity assay (VWF:RCo) that uses the antibiotic ristocetin to induce
      plasma VWF binding to glycoprotein (GP) IbIXV on target platelets. VWF-collagen
      binding assays, depending on the type of collagen used, can improve the detection
      of forms of VWD with high molecular weight VWF multimer loss, although the best
      method is debatable. A number of innovations have been applied to VWF:RCo (which
      is commonly performed on an aggregometer), including replacing the target
      platelets with immobilized GPIbalpha, and quantification by an enzyme-linked
      immunosorbent assay (ELISA), immunoturbidimetric, or chemiluminescent end-point.
      Some common polymorphisms in the VWF gene that do not cause bleeding are
      associated with falsely low VWF activity by ristocetin-dependent methods. To
      overcome the need for ristocetin, some new VWF activity assays use gain-of
      function GPIbalpha mutants that bind VWF without the need for ristocetin, with an
      improved precision and lower limit of detection than measuring VWF:RCo by
      aggregometry. ELISA of VWF binding to mutated GPIbalpha shows promise as a method
      to identify gain-of-function defects from type 2B VWD. The performance
      characteristics of many new VWF activity assays suggest that the detection of
      VWD, and monitoring of VWD therapy, by clinical laboratories could be improved
      through adopting newer generation VWF assays. 

PMID- 24750681
TI  - Evaluation of an automated method for measuring von Willebrand factor activity in
      clinical samples without ristocetin.
AB  - INTRODUCTION: The development of an automated, von Willebrand factor (VWF)
      activity assay, Innovance((r)) VWF Ac (VWF:Ac), which measures VWF binding to the
      platelet receptor glycoprotein Ibalpha without ristocetin, led us to evaluate the
      assay for diagnosing von Willebrand disease (VWD) and monitoring therapy.
      METHODS: After validating that the assay could be performed on an instrument from
      a different manufacturer, we compared VWF:Ac to VWF ristocetin cofactor activity
      (VWF:RCo) findings, including ratios of activity/antigen, for 100 healthy
      controls and 262 consecutive clinical samples from 217 patients (197 adults, 64
      children, n = 1 age unknown) referred for VWF testing. RESULTS: There was
      excellent correlation (R(2) = 0.96) between VWF:Ac results run at two different
      sites on two different instruments. VWF:Ac had greater precision and sensitivity
      to low levels of VWF than the VWF:RCo method. Although there was good correlation
      between VWF:Ac and VWF:RCo results among healthy controls and patient subjects,
      VWF:Ac results were undetectable and/or significantly lower than VWF:RCo among
      patients who had types 2A, 2B, or 2M VWD. Additionally, a higher proportion of
      patient samples were classified as showing qualitative defects using the VWF:Ac
      compared with VWF:RCo method. While most samples drawn on VWD therapy had similar
      VWF levels by VWF:Ac and VWF:RCo, a type 2B VWD subject on replacement had much
      lower activity estimated by VWF:Ac. CONCLUSION: We conclude that Innovance((r))
      VWF Ac is suitable for the diagnosis, classification, and monitoring of VWD, and
      that it has a number of advantages over VWF:RCo method.

PMID- 24750682
TI  - Antiphospholipid antibody testing and standardization.
AB  - The laboratory criteria that define patients with antiphospholipid syndrome (APS)
      include lupus anticoagulant (LAC), anticardiolipin antibodies and anti-beta2
      glycoprotein I antibodies (abeta2GPI). All assays show methodological
      shortcomings and the combination of the three tests, each with different
      sensitivity and specificity, and hence, differences in clinical utility make the
      laboratory diagnosis of APS challenging. Consensus guidelines and proposals for
      antiphospholipid antibodies (aPL) testing have been published in the last 20
      years and have led to a substantial improvement. Despite efforts so far,
      standardization is not reached yet, but progress has been made. On-going efforts
      to reduce the interlaboratory/interassay variations remain important; even an
      absolute standardization cannot be feasibly achieved. Taking into account the
      methodological shortcomings of the means we have available, more detailed
      guidelines may help in adequate performance of aPL testing. This review will
      focus on the efforts and achievements in standardization and on the weaknesses
      and strengths of the current available laboratory methods.

PMID- 24750683
TI  - Commonalities and contrasts in recent guidelines for lupus anticoagulant
      detection.
AB  - Updates to guidelines covering lupus anticoagulant (LA) detection have recently
      been published by the International Society on Haemostasis and Thrombosis (ISTH)
      and British Committee for Standards in Haematology (BCSH), in 2009 and 2012,
      respectively. The Clinical and Laboratory Standards Institute (CLSI) published
      its first LA guideline in 2014. Cross-panel agreement exists on sample
      manipulation, use of dRVVT analysis, conversion of clotting times to ratios,
      calculations to demonstrate phospholipid dependence, mixing test interpretation
      and provision of interpretive reporting. Whilst ISTH restricts assay choice to
      just dRVVT and activated partial thromboplastin time, BCSH and CLSI consider the
      case for additional tests. All panels acknowledge the potential for false
      negative mixing tests, yet they remain mandated by ISTH and BCSH, the latter,
      however, indicating that a negative mixing test need not exclude a LA if testing
      on undiluted plasma is unequivocal. CLSI reprioritizes test order to screen
      confirm-mix to reduce false-negative reporting when antibodies are diluted to
      undetectable levels in mixing tests. Recommendations differ on how to derive cut
      off levels, particularly in view of the realities of relatively low donor
      numbers. Each guideline considers testing of anticoagulated patients, BCSH and
      CLSI endorsing Taipan snake venom time as a useful supplementary assay in
      patients on vitamin K antagonists. Although full consensus is not apparent, these
      publications represent significant moves towards engendering common practices. 

PMID- 24750684
TI  - Tracking down contact activation - from coagulation in vitro to inflammation in
      vivo.
AB  - The contact system is a volatile and versatile enzyme system in blood plasma that
      responds to the presence of nonphysiological surface materials by spontaneous
      generation of enzymatic activity. In subsequent steps, it can trigger blood
      coagulation and is responsible for the generation of the proinflammatory peptide
      bradykinin. The physiological role of the contact system is presently unknown,
      but it is commonly used to trigger coagulation in a diagnostic setting. In this
      three-part review, we will first describe the molecular mechanisms that drive
      contact activation on nonphysiological materials. Next, we will summarize and
      compare a number of bioassays, which are commonly used to investigate the contact
      system in health and disease. Finally, we will discuss recent findings from both
      fundamental and clinical studies on the contributions of contact system to
      cardiovascular, infectious, and inflammatory disease. 

PMID- 24750685
TI  - Aplastic anemia: possible associations with lymphoproliferative neoplasms.
AB  - Aplastic anemia (AA) may precede, co-occur, or follow a lymphoproliferative
      neoplasm. The best molecularly clarified scenario is that of concurrent AA and
      unsuspected (occult) T-cell large granular lymphocyte leukemia. Several reported
      cases of AA and concurrent small B-cell lymphomas/leukemias and Hodgkin lymphomas
      suggest also a possible link to simultaneous or preceding AA that might be sought
      in an antineoplastic immunological attempt to 'eradicate' the underlying
      malignant clone. The 'immuno-deregulatory' potential and the direct cytotoxicity
      of regimens used for lymphoma therapy might be able to trigger AA in cases
      evolving after lymphoma treatment too. Alternative explanations of AA associated
      with lymphoproliferative disorders might be particular (immuno-)genetic patient
      backgrounds predisposing to both AA and lymphoid neoplasms or exposures to
      environmental factors, increasing the risk for both diseases. Finally, the most
      common causal relationship of AA and lymphoma is that of immunosuppression- or
      allogeneous hematopoietic stem cell transplantation-associated
      posttransplantational lymphoproliferative disorders in AA patients, who are
      treated in the respective manner. As all above scenarios are differently
      (specifically) therapeutically approachable and accompanied by diverse outcomes,
      they should be actively sought for and diagnosed as precisely as possible. This
      review summarizes the current knowledge on associations between AA and
      lymphoproliferative neoplasms. 

PMID- 24750686
TI  - Rare hereditary red blood cell enzymopathies associated with hemolytic anemia -
      pathophysiology, clinical aspects, and laboratory diagnosis.
AB  - Hereditary red blood cell enzymopathies are genetic disorders affecting genes
      encoding red blood cell enzymes. They cause a specific type of anemia designated
      hereditary nonspherocytic hemolytic anemia (HNSHA). Enzymopathies affect cellular
      metabolism, which, in the red cell, mainly consists of anaerobic glycolysis, the
      hexose monophosphate shunt, glutathione metabolism, and nucleotide metabolism.
      Enzymopathies are commonly associated with normocytic normochromic hemolytic
      anemia. In contrast to other hereditary red cell disorders such as membrane
      disorders or hemoglobinopathies, the morphology of the red blood cell shows no
      specific abnormalities. Diagnosis is based on detection of reduced specific
      enzyme activity and molecular characterization of the defect on the DNA level.
      The most common enzyme disorders are deficiencies of glucose-6-phosphate
      dehydrogenase (G6PD) and pyruvate kinase (PK). However, there are a number of
      other enzyme disorders, often much less known, causing HNSHA. These disorders are
      rare and often underdiagnosed, and the purpose of this review. In this brief
      review, we provide an overview of clinically relevant enzymes, their function in
      red cell metabolism, and key aspects of laboratory diagnosis. 

PMID- 24750687
TI  - Acquired hemophilia: a case report and review of the literature.
AB  - Acquired hemophilia A (AHA) is a rare bleeding disorder caused by autoantibodies
      against clotting factor VIII (FVIII). FVIII autoantibody is characterized as
      polyclonal immunoglobulin G directed against the FVIII procoagulant activity.
      This disease occurs most commonly in the elderly population and with
      preponderance of men in nonpregnancy-related AHA. There are well-established
      clinical associations with AHA such as malignancy, other autoimmune diseases and
      pregnancy. However, up to 50% of reported cases remain idiopathic. The clinical
      manifestation of AHA includes mostly spontaneous hemorrhages into skin, muscles
      and soft tissues, or mucous membranes. AHA should be suspected when a patient
      with no previous history of bleeding presents with bleeding and an unexplained
      prolonged activated partial thromboplastin time. The diagnosis is confirmed in
      the laboratory by the subsequent identification of reduced FVIII levels and FVIII
      inhibitor titration. There is a high mortality, making prompt diagnosis and
      treatment vitally important. The principles of treatment consist in controlling
      the bleeding and eradicating the inhibitor. Because of the overall high relapse
      rate (15-33%), it is also recommended to follow up these patients. The review
      summarizes what is currently known about the epidemiology, pathogenesis, clinical
      features, diagnosis, treatment and prognosis of AHA and starts with a case
      report. 

PMID- 24750688
TI  - (Cleaved) CK18 serum and tissue expression levels differentiate acute HCV
      reinfection from acute rejection in liver allografts.
AB  - BACKGROUND & AIMS: Orthotopic liver transplantation (OLT) is the sole therapeutic
      option to cure end-stage liver diseases including HCV-related cirrhosis. Timely
      and precise differentiation of relevant acute HCV reinfection from acute
      rejection after OLT is vital for appropriate therapy. Aim of this study was to
      evaluate the usefulness of (non-) invasive apoptosis (M30) and necrosis (M65)
      determination in the differential diagnosis of acute (and chronic) HCV
      reinfection vs. acute rejection in liver allografts. METHODS: Serum samples and
      liver biopsy tissues were available from 76 patients including a control group
      (19* NAFL, 19* NASH, 16* acute rejection, 11* acute and 11* chronic HCV
      reinfection) and were analysed using M30- and M65 ELISAs (M30S, M65S) and M30
      immunohistochemistry (M30H). Clinical and serological data were collected.
      RESULTS: M30S, M65S and M30H were highly correlated with diagnostic groups in the
      total cohort (all P < 0.0001). M30S, M65S and M30H were independently able to
      differentiate acute HCV reinfection from acute rejection (P = 0.048, P = 0.001, P
      = 0.010) with moderate to excellent diagnostic accuracy (sensitivity,
      specificity, cut-off-value in M30S: 70%, 75%, 1025 U/L; M65S: 100%, 92%, 1308
      U/L; M30H: 73%, 88%, 0.3%). CONCLUSIONS: M30-, M65-ELISAs and M30
      immunohistochemistry are potential useful tools in differentiating acute HCV
      reinfection from acute rejection facilitating both speed and accuracy of the
      diagnostic process for the clinician and hepatopathologist. In this context, M65S
      provided superior diagnostic characteristics compared to M30-based methods.
      However, being the first analysis of (cleaved) CK18 serum and tissue expression
      levels in this context, the results need to be verified in further studies.

PMID- 24750689
TI  - Transformative Lifestyle Change: key to sustainable weight loss among women in a
      post-partum diet and exercise intervention.
AB  - The increase in overweight and obesity among women is a growing concern, and
      reproduction is associated with persistent weight gain. We have shown that
      dietary behavioural modification treatment, with or without exercise, results in
      weight loss and maintenance of weight loss. The aim of this study was to provide
      an explanatory model of how overweight and obese women achieve weight loss
      during, and after, participating in a post-partum diet and/or exercise
      intervention. Using Grounded Theory, we performed and analysed 29 interviews with
      21 women in a 12-week Swedish post-partum lifestyle intervention with a 9-month
      follow-up. Interviews were made after the intervention and at the 9-month follow
      up. To overcome initial barriers to weight loss, the women needed a 'Catalytic
      Interaction' (CI) from the care provider. It depended on individualised,
      concrete, specific and useful information, and an emotional bond through joint
      commitment, trust and accountability. Weight loss was underpinned by gradual
      introduction of conventional health behaviours. However, the implementation
      depended on the experience of the core category process 'Transformative Lifestyle
      Change' (TLC). This developed through a transformative process of reciprocal
      changes in cognitions, emotions, body, environment, behaviours and perceived
      self. Women accomplishing the stages of the TLC process were successful in weight
      loss, in contrast to those who did not. The TLC process, dependent on initiation
      through CI, led to implementation and integration of recognised health
      behaviours, resulting in sustainable weight loss. The TLC model, including the CI
      construct and definition of barriers, facilitators and strategies provides an
      explanatory model of this process. 

PMID- 24750690
TI  - Construction of a cDNA library for miniature pig mandibular deciduous molars.
AB  - BACKGROUND: The miniature pig provides an excellent experimental model for tooth
      morphogenesis because its diphyodont and heterodont dentition resembles that of
      humans. However, little information is available on the process of tooth
      development or the exact molecular mechanisms controlling tooth development in
      miniature pigs or humans. Thus, the analysis of gene expression related to each
      stage of tooth development is very important. RESULTS: In our study, after serial
      sections were made, the development of the crown of the miniature pigs'
      mandibular deciduous molar could be divided into five main phases: dental lamina
      stage (E33-E35), bud stage (E35-E40), cap stage (E40-E50), early bell stage (E50
      E60), and late bell stage (E60-E65). Total RNA was isolated from the tooth germ
      of miniature pig embryos at E35, E45, E50, and E60, and a cDNA library was
      constructed. Then, we identified cDNA sequences on a large scale screen for cDNA
      profiles in the developing mandibular deciduous molars (E35, E45, E50, and E60)
      of miniature pigs using Illumina Solexa deep sequencing. Microarray assay was
      used to detect the expression of genes. Lastly, through Unigene sequence analysis
      and cDNA expression pattern analysis at E45 and E60, we found that 12 up
      regulated and 15 down-regulated genes during the four periods are highly
      conserved genes homologous with known Homo sapiens genes. Furthermore, there were
      6 down-regulated and 2 up-regulated genes in the miniature pig that were highly
      homologous to Homo sapiens genes compared with those in the mouse. CONCLUSION:
      Our results not only identify the specific transcriptome and cDNA profile in
      developing mandibular deciduous molars of the miniature pig, but also provide
      useful information for investigating the molecular mechanism of tooth development
      in the miniature pig.

PMID- 24750691
TI  - HIV Tat protein affects circadian rhythmicity by interfering with the circadian
      system.
AB  - OBJECTIVES: Sleep disorders are common in patients with HIV/AIDS, and can lead to
      poor quality of life. Although many studies have investigated the aetiology of
      these disorders, it is still unclear whether impaired sleep quality is associated
      with HIV itself, social problems, or side effects of antiretroviral therapy
      (ART). Moreover, despite its known neurological associations, little is known
      about the role of the trans-activator of transcription (Tat) protein in sleep
      disorders in patients with HIV/AIDS. The purpose of this study was to test the
      hypothesis that the sleep quality of patients with HIV/AIDS affected by an
      altered circadian rhythm correlates with cerebrospinal HIV Tat protein
      concentration. METHODS: Ninety-six patients with HIV/AIDS between 20 and 69 years
      old completed the Pittsburgh Sleep Quality Index. Their circadian rhythm
      parameters of blood pressure, Tat concentration in cerebrospinal fluid, melatonin
      concentration, CD4 cell count and HIV RNA viral load in serum were measured.
      RESULTS: The circadian amplitude of systolic blood pressure and the score for
      sleep quality (Pittsburgh Sleep Quality Index) were negatively correlated with
      HIV Tat protein concentration, while the melatonin value was positively
      correlated with Tat protein concentration. CONCLUSIONS: The HIV Tat protein
      affects circadian rhythmicity by interfering with the circadian system in
      patients with HIV/AIDS and further increases the melatonin excretion value. A Tat
      protein-related high melatonin value may counteract HIV-related poor sleep
      quality during the progression of HIV infection. This study provides the first
      clinical evidence offering an explanation for why sleep quality did not show an
      association with progression of HIV infection in previous studies.

PMID- 24750692
TI  - Bat flight and zoonotic viruses.
AB  - Bats are sources of high viral diversity and high-profile zoonotic viruses
      worldwide. Although apparently not pathogenic in their reservoir hosts, some
      viruses from bats severely affect other mammals, including humans. Examples
      include severe acute respiratory syndrome coronaviruses, Ebola and Marburg
      viruses, and Nipah and Hendra viruses. Factors underlying high viral diversity in
      bats are the subject of speculation. We hypothesize that flight, a factor common
      to all bats but to no other mammals, provides an intensive selective force for
      coexistence with viral parasites through a daily cycle that elevates metabolism
      and body temperature analogous to the febrile response in other mammals. On an
      evolutionary scale, this host-virus interaction might have resulted in the large
      diversity of zoonotic viruses in bats, possibly through bat viruses adapting to
      be more tolerant of the fever response and less virulent to their natural hosts. 

PMID- 24750694
TI  - Extensively drug-resistant Streptococcus pneumoniae, South Korea, 2011-2012.
AB  - To better understand extensively drug resistant Streptococcus pneumoniae, we
      assessed clinical and microbiological characteristics of 5 extensively drug
      resistant pneumococcal isolates. We concluded that long-term care facility
      residents who had undergone tracheostomy might be reservoirs of these
      pneumococci; 13- and 23-valent pneumococcal vaccines should be considered for
      high-risk persons; and antimicrobial drugs should be used judiciously. 

PMID- 24750693
TI  - Assessing parental self-efficacy for obesity prevention related behaviors.
AB  - BACKGROUND: Reliable, valid and theoretically consistent measures that assess a
      parent's self-efficacy for helping a child with obesity prevention behaviors are
      lacking. OBJECTIVES: To develop measures of parental self-efficacy for four
      behaviors: 1) helping their child get at least 60 minutes of moderate intensity
      physical activity every day, 2) helping one's child consume five servings of
      fruits and vegetables each day, 3) limiting sugary drinks to once a week, and 4)
      limiting consumption of fruit juice to 6 ounces every day. METHODS: Sequential
      methods of scale development were used. An item pool was generated based on
      theory and qualitative interviews, and reviewed by content experts. Scales were
      administered to parents or legal guardians of children 4-10 years old. The item
      pool was reduced using principal component analysis. Confirmatory factor analysis
      tested the resulting models in a separate sample. SUBJECTS: 304 parents, majority
      were women (88%), low-income (61%) and single parents (61%). Ethnic distribution
      was 40% Black and 37% white. RESULTS: All scales had excellent fit indices:
      Comparative fit index> .98 and chi-squares (Pediatrics 120 Suppl 4:S229-253,
      2007) = .85 - 7.82. Alphas and one-week test-retest ICC's were >=.80. Significant
      correlations between self-efficacy scale scores and their corresponding behaviors
      ranged from .13-.29 (all p < 0.03). CONCLUSIONS: We developed four, four-item
      self-efficacy scales with excellent psychometric properties and construct
      validity using diverse samples of parents. TRIAL REGISTRATION:  CLINICAL TRIAL
      REGISTRATION: NCT01768533.

PMID- 24750695
TI  - Neutrophils as new conductors of vascular homeostasis.

PMID- 24750696
TI  - The clearance concept with special reference to determination of glomerular
      filtration rate in patients with fluid retention.
AB  - In subjects without fluid retention, the total plasma clearance of a renal
      filtration indicator (inulin, (99m) Tc-DTPA, (51) Cr-EDTA) is close to the
      urinary plasma clearance. Conversely, in patients with fluid retention (oedema,
      pleural effusions, ascites), there is a substantial discrepancy between the total
      plasma clearance and the urinary plasma clearance. This is owing to delayed
      indicator distribution to smaller or larger parts of the interstitial space,
      which in patients with ascites may simulate a peritoneal dialysator. In patients
      with fluid retention, urinary plasma clearance should be assessed to obtain a
      correct measurement of the glomerular filtration rate (GFR). In theory, total
      plasma clearance with late samples (24-h, 48-h) may be applied in patients with
      fluid retention, but validation hereof has not been performed. Until such studies
      are completed, it is recommended that patients with fluid retention have their
      GFR measured by a urinary plasma clearance technique with controlled quantitative
      urinary sampling within a few hours after indicator injection. 

PMID- 24750697
TI  - Brain targets: can you believe your own eyes?
AB  - The unquestionable advantages provided by modern neuroimaging techniques have
      recently led some to question the duty of the neurologist, traditionally
      struggling first and foremost to establish the semeiotic localization of brain
      lesions and only then to interpret them. The present brief report of six clinical
      patients who came recently to our attention aims to emphasize that the
      interpretation of neuroimaging results always requires integration with
      anamnestic, clinical and laboratory data, together with knowledge of nosography
      and the literature. The solutions of the reported cases always originated from
      close interaction between the neurologist and the neuroradiologist, based on the
      initial diagnostic uncertainty linked to the finding of isolated or multiple
      brain target or ring lesions, too often considered paradigmatic examples of the
      pathognomonic role of neuroimaging. 

PMID- 24750698
TI  - Predicting arterial injuries after penetrating brain trauma based on scoring
      signs from emergency CT studies.
AB  - The objective of this study was to determine the accuracy of individual
      radiologists in detection of vascular injury in patients after penetrating brain
      injury (PBI) based on head CT findings at admission. We retrospectively evaluated
      54 PBI patients who underwent admission head CT and digital subtraction
      angiography (DSA), used here as a reference standard. Two readers reviewed the CT
      images to determine the presence or absence of the 29 CT variables of injury
      profile and quantified selected variables. Four experienced trauma radiologists
      and one neuroradiologist assigned their own specific scores for each CT variable,
      a high score indicative of a high probability of artery injury. A sixth set
      consisted of the average score obtained from the five sets, generated by five
      experts. Receiver operating characteristic (ROC) curves were constructed for each
      set to assess the diagnostic performance of an individual radiologist in
      predicting an underlying vascular injury. The area under ROC curve (AUC) was
      higher for CT scores obtained from the sixth set (average of five sets of scores)
      of variable rank score 0.75 (95% CI 0.62-0.88) and for the rest of the data sets,
      the value ranged from 0.70 (95% CI 0.56-0.84) to 0.74 (95% CI 0.6-0.88). In
      conclusion, radiologists may be able to recommend DSA with a fair accuracy rate
      in selected patients, deemed 'high-risk' for developing intracranial vascular
      injuries after PBI based on admission CT studies. A better approach needs to be
      developed to reduce the false positive rate to avoid unnecessary emergency DSA. 

PMID- 24750699
TI  - Into the septum I go, a case of bilateral ectopic infraorbital nerves: a not-to
      miss preoperative sinonasal CT variant.
AB  - An ectopic course of the infraorbital nerve is a very rare anatomical variant of
      the sinonasal anatomy that carries the risk of inadvertent nerve injury during
      functional endoscopic sinus surgery. We describe herein a case of bilateral
      ectopic course of the infraorbital nerve into a maxillary sinus septum detected
      on computed tomography in a patient complaining of chronic headache and facial
      pain. 

PMID- 24750700
TI  - Goldenhar syndrome associated with contralateral agenesis of the internal carotid
      artery.
AB  - Congenital absence of the internal carotid artery (ICA) is an extremely rare
      vascular anomaly. Aplasia and displacement of the horizontal portion of the
      petrous carotid artery have been described in a patient with mandibulofacial
      dysostosis. To the best of our knowledge, the association between Goldenhar
      syndrome and ipsilateral ICA agenesis has emerged only in one case documented in
      the medical literature to date. We describe here a case that illustrates the
      association of Goldenhar syndrome with contralateral agenesis of the ICA
      incidentally detected on brain magnetic resonance imaging and subsequently
      confirmed on magnetic resonance angiography and high resolution computed
      tomography. 

PMID- 24750701
TI  - Arachnoid cyst of the cavum velum interpositum in a septuagenarian: radiological
      features and differential diagnosis.
AB  - The cavum velum interpositum (CVI) is a thin, triangular-shaped cerebrospinal
      fluid (CSF)-filled space between the lateral ventricles that lies below the
      fornices and above the third ventricle. It is a normal variant seen in premature
      and newborn infants and usually disappears with brain maturation. CVI is rarely
      seen in adults as a persistent primitive structure. Although moderate cystic
      dilatation of the CVI may sometimes be observed, a true large cyst is extremely
      rare with only a handful of reported cases, mostly in children and adolescents.
      We describe the case of CVI arachnoid cyst diagnosed on imaging in a
      septuagenarian with the complaint of occasional headaches. 

PMID- 24750702
TI  - Functional connectivity MRI and post-operative language performance in temporal
      lobe epilepsy: initial experience.
AB  - Anterior temporal lobectomy is an effective treatment for drug-resistant epilepsy
      of temporal origin, although new language impairment may develop after surgery.
      Since correlations between functional connectivity (FC) MRI of the language
      network and verbal-IQ performance before surgery have recently been reported, we
      investigated the existence of correlations between the preoperative FC of the
      language network and post-operative verbal-IQ decline. FC between nodes of the
      language network of the two hemispheres (Interhemispheric-FC) and within nodes of
      the left hemisphere (LH-FC) and language lateralization indexes were estimated in
      five right-handed patients with non-tumoral left temporal lobe epilepsy
      undergoing anterior temporal lobectomy. Correlations between preoperative FC
      measures and lateralization indexes, and the post-operative (12 months)
      neuropsychological verbal-IQ decline were investigated. Verbal-IQ decline was
      inversely correlated with the degree of left lateralization and directly
      correlated with the strength of Interhemispheric-FC. No significant correlation
      was found between LH-FC and post-operative verbal-IQ change. The results from
      this limited number of patients suggest that a stronger preoperative connectivity
      between homologue regions, associated with the absence of a definite hemispheric
      lateralization, appears to be an unfavorable prognostic biomarker. 

PMID- 24750703
TI  - Neuroradiology and histopathology in two cases of adult medulloblastoma.
AB  - Medulloblastoma (MB) is the most common central nervous system neoplasm in
      children and only rarely presents in the adult population. Recent molecular
      biology findings have characterized MB as a heterogeneous neoplasm distinguished
      by well-defined tumour subsets each with specific histologic and molecular
      features. Available immunohistochemical stains can now be used to differentiate
      the distinct molecular types of MB. This report analyzed the histopathologic and
      neuroradiologic features of two new cases of adult MB. Imaging studies in these
      patients revealed the morphological appearance of high-grade, well-circumscribed
      heterogeneous tumours with necrosis, located laterally within the posterior
      cranial fossa. Histopathology of resected samples demonstrated high-grade tumours
      (WHO grade IV) containing sheets of undifferentiated neural cells with high
      mitotic activity and evidence of necrosis. The histopathologic and molecular
      characteristics of these cases of MB are reviewed for potential applications in
      new molecular methods of imaging. 

PMID- 24750704
TI  - Neural stem cells and glioblastoma.
AB  - Glioblastoma multiforme represents one of the most common brain cancers with a
      rather heterogeneous cellular composition, as indicated by the term "multiforme".
      Recent reports have described the isolation and identification of cancer neural
      stem cells from human adult glioblastoma multiforme, which possess the capacity
      to establish, sustain, and expand these tumours, even under the challenging
      settings posed by serial transplantation experiments. Our study focused on the
      distribution of neural cancer stem cells inside the tumour. The study is divided
      into three phases: removal of tumoral specimens in different areas of the tumour
      (centre, periphery, marginal zone) in an operative room equipped with a 1.5 T
      scanner; isolation and characterization of neural cancer stem cells from human
      adult glioblastoma multiforme; identification of neural cancer stem cell
      distribution inside the tumour. 

PMID- 24750705
TI  - Extraneural metastasis of an ependymoma: a rare occurrence.
AB  - Extraneural metastases of ependymoma are very rare, and have been reported in the
      lungs, lymph nodes, pleura, mediastinum, liver, diaphragmatic muscle, and bone.
      We describe the radiological findings of pathologically proven lung metastases
      from an anaplastic ependymoma. The tumor which arose in the posterior fossa was
      first diagnosed in 2007 when first surgical resection was performed outside our
      institute. Multiple operations were performed after that due to tumor relapse.
      Multiple lung nodules were discovered incidentally during a VP shunt survey.
      Biopsy from the lung nodules displayed identical histomorphology to the primary
      brain tumor. 

PMID- 24750706
TI  - Multisegmental diffuse intradural extramedullary ependymoma. An extremely rare
      case.
AB  - Ependymoma has been described typically as an intramedullary tumour derived from
      ependymal cells with a predominance in women in the fifth decade of life. Pain is
      the most frequent symptom. Intradural extramedullary presentation is rarely
      described and almost always as a unique lesion. We describe a 53-year-old man
      with multi-segmental diffuse intradural extramedullary ependymoma with
      progressive lower leg hypoesthesia with regular motility. The patient's
      neurologic condition improved after surgery. 

PMID- 24750707
TI  - Symptomatic anterior cerebral artery vasospasm after brainstem hemangioblastoma
      resection. A case report.
AB  - Diffuse cerebral vasospasm is a rare complication after brain tumour resection as
      opposed to that following an aneurysmal subarachnoid haemorrhage. Sellar tumours
      are among the most common pathologies and locations associated with this
      complication. Removal of posterior cranial fossa lesions is uncommonly associated
      with vasospasm, with only nine reported cases. We describe a case of diffuse
      symptomatic vasospasm mainly involving the right anterior cerebral artery,
      angiographically confirmed, after resection of a haemangioblastoma of the medulla
      in an adult patient with von Hippel-Lindau disease. The possible pathogenesis of
      this phenomenon is discussed. 

PMID- 24750708
TI  - A chronic intracerebral fluid hematoma.
AB  - Intracerebral hematoma usually resolves and a chronic fluid hematoma is rare. We
      describe a rare case of intracerebral fluid hematoma. This report describes a
      case of intracerebral fluid hematoma mimicking a brain tumor and discusses the
      characteristics of this condition. A 70-year-old woman had a six-month history of
      memory disturbance. Computed tomography scan showed a low-density lesion with a
      partial high-density area in the right frontal lobe. MRI revealed a lesion of the
      main cystic portion showing high intensity on both T1 and T2 weighted images with
      a low-intensity solid portion in the anteromedial side. The lesion was adjacent
      to the lateral ventricle. Craniotomy was carried out and the lesion was removed.
      Pathological examination of the solid portion revealed that the diagnosis was
      reactive changes due to intracerebral hemorrhage. In our case, there was a
      possibility that the hematoma was diluted with cerebrospinal fluid, and
      coagulation might have been prevented. 

PMID- 24750709
TI  - Spontaneous regression and recurrence of a tumefactive perivascular space.
AB  - Perivascular spaces can occasionally appear mass-like (tumefactive or giant
      perivascular space), and can be associated with clinical symptoms. Spontaneous
      regression of a tumefactive perivascular space is a very rare phenomenon with
      only two reported cases in the English medical literature. Spontaneous regression
      of a tumefactive perivascular space along with resolution of clinical symptoms,
      followed by spontaneous recurrence associated with symptom recurrence is an
      extremely rare occurrence, which to the best of our knowledge, has not been
      reported in the medical literature. We describe a case of spontaneous regression
      of a tumefactive perivascular space, three years after its initial detection,
      followed by spontaneous recurrence after two years. 

PMID- 24750710
TI  - Flat panel angiography images in the post-operative follow-up of surgically
      clipped intracranial aneurysms.
AB  - Cerebral aneurysms must be monitored for varying periods after surgical and/or
      endovascular treatment and the duration of follow-up will depend on the type of
      therapy and the immediate post-operative outcome. Surgical clipping for
      intracranial aneurysms is a valid treatment but the metal clips generate
      artefacts so that follow-up monitoring still relies on catheter angiography. This
      study reports our preliminary experience with volumetric angiography using a
      Philips Allura Xper FD biplane system in the post-operative monitoring of
      aneurysm residues or major vascular changes following the surgical clipping of
      intracranial aneurysms. Volumetric angiography yields not only volume-rendered
      (VR) images, but a volume CT can also be reconstructed at high spatial and
      contrast resolution from a single acquisition, significantly enhancing the
      technique's diagnostic power. Between August 2012 and April 2013, we studied 19
      patients with a total of 26 aneurysms treated by surgical clipping alone or in
      combination with endovascular treatment. All patients underwent standard post
      operative angiographic follow-up including a rotational volumetric acquisition.
      Follow-up monitoring disclosed eight aneurysm residues whose assessment was
      optimal after surgical clipping both in patients with one metal clip and in those
      with two or more clips. In addition, small residues (1.3 mm) could be monitored
      together with any change in the calibre or course of vessels located adjacent to
      the clips. In conclusion, flat panel volume CT is much more reliable than the old
      3D acquisitions that yielded only VR images. This is particularly true in
      patients with small aneurysm residues or lesions with multiple metal clips. 

PMID- 24750711
TI  - Endovascular treatment in an unusual case of direct carotid cavernous fistula.
AB  - We describe a unique and unusual case of post-traumatic direct carotid cavernous
      fistula (CCF) with occluded proximal internal carotid artery and CCF filling from
      the contralateral side with retrograde cortical venous reflux. A male patient
      presented with intracranial haemorrhage due to cortical venous reflux. He was
      treated endovascularly through a contralateral approach by coiling the cavernous
      sinus and occluding the distal internal carotid artery at the fistulous site with
      glue. 

PMID- 24750712
TI  - Long-term treatment outcomes after intravascular ultrasound evaluation and stent
      placement for atherosclerotic subclavian artery obstructive lesions.
AB  - The objective of this study was to determine long-term outcomes after stent
      placement for subclavian artery (SA) obstructive lesions assisted by
      intraoperative intravascular ultrasound (IVUS). The study included 25 lesions in
      24 patients who underwent stent placement assisted by intraoperative IVUS for
      subclavian artery stenosis or obstruction at our hospital between January 2003
      and August 2010. Outcome was evaluated based on the results within 30
      postoperative days (technical success rate, improvement in upper extremity
      ischemia, steal syndrome, left-right blood pressure difference, and perioperative
      complications) and the results after 30 postoperative days (incidence of
      vertebrobasilar artery territory infarction and restenosis). Stent placement and
      vessel dilatation were successful in all patients, without perioperative
      complications. Upper extremity ischemia, steal syndrome, and left-right blood
      pressure difference disappeared in all cases. During follow-up observation (6-96
      months; median 51 months), no restenosis occurred at the stent placement site in
      any patient. In one case, four years after initial treatment, stenosis was noted
      proximal to the stent placement site. Satisfactory long-term as well as short
      term outcomes were achieved after stent placement for SA obstructive lesions
      assisted by intraoperative IVUS evaluation. 

PMID- 24750713
TI  - Coexistence of cavernous hemangioma and other vascular malformations of the
      orbit. A report of three cases.
AB  - Coexistence of orbital cavernous hemangioma and other vascular malformations is
      unusual and few cases have been reported. We describe the clinical and
      radiological features of three cases of orbital cavernous hemangiomas associated
      with other vascular malformations, selected reviewing a series of 181 cases of
      cavernous hemangiomas. All patients were males (age ranging from 43 to 67 years)
      without vascular systemic disorders and/or a clinical syndrome. They experienced
      slow progressive exophthalmos. One of them developed acute pulsatile proptosis
      (case 2), while another experienced slow progressive diplopia (case 3). In one
      case vascular lesions were bilateral (case 3) and in two patients two different
      lesions coexisted in the same orbit (cases 1 and 2). All patients underwent
      surgical excision, which was partial in two cases. Two patients had cavernous
      hemangiomas in association with a venous malformation (a varix in case 1 and a
      lymphangioma in case 2), while in the other ones (case 3) cavernous hemangioma
      was associated with a low-flow arteriovenous malformation. No patient denied
      visual impairment postoperatively. Few cases of orbital cavernous hemangiomas
      coexisting with other vascular malformations have been reported in the
      literature. This entity seems to be an association of different variants of
      orbital vascular malformations, presenting with a wide spectrum of clinical forms
      and probably with the same pathogenesis. 

PMID- 24750714
TI  - Use of apparent diffusion coefficient values for diagnosis of pediatric posterior
      fossa tumors.
AB  - We prospectively compared the ability of neuroradiologists to diagnose
      medulloblastoma with novice raters using only apparent diffusion coefficient
      (ADC) values measured on ADC maps. One hundred and three pediatric patients with
      pre-operative magnetic resonance imaging scans showing a posterior fossa tumor
      with histological verification were retrospectively identified from a ten-year
      period at a tertiary care medical center. A single observer measured the lowest
      ADC values in all tumors to determine the mean minimum ADC (ADCmin) value that
      provided greatest accuracy in distinguishing medulloblastomas from other tumors,
      which was determined to be 0.66*10(-3) mm(2)/s. Imaging studies, including ADC
      maps, from 90 patients were provided to two neuroradiologists, who provided a
      diagnosis, which was later dichotomized as medulloblastoma or other. Two medical
      students measured ADCmin within tumors and those with ADCmin < 0.66*10(-3)
      mm(2)/s were recorded as medulloblastoma; any other value was recorded as other.
      Diagnostic accuracy was measured. ADCmin values allowed a correct identification
      of lesions as either medulloblastoma or other in 91% of cases. After diagnoses by
      the two neuroradiologists were categorized as either medulloblastoma or other,
      their diagnoses were correct in 90% and 84% of cases, respectively. In 19 cases,
      at least one neuroradiologist was incorrect; the addition of ADC values to
      clinical interpretation would have allowed a correct diagnosis in 63% of such
      cases. Diagnostic accuracy based on ADC values by medical students was comparable
      to that of subspecialty-trained neuroradiologists. Our findings suggest that the
      addition of ADC values to standard film interpretation may improve the diagnostic
      rate for these tumors. 

PMID- 24750715
TI  - Benign external hydrocephalus in infants. A single centre experience and
      literature review.
AB  - External hydrocephalus (EH) is a benign clinical entity in which macrocephaly is
      associated with an increase in volume of the subarachnoid space, especially
      overlying both frontal lobes, and a normal or only slight increase in volume of
      the lateral ventricles. Several pathogenic hypotheses have been proposed but the
      most accredited theory seems to be delayed maturation of the arachnoid villi.
      There is a consensus that this is a benign entity, correlated to a familial
      predisposition and, in some cases, inheritance. CT and MRI are very important to
      make a diagnosis but also to establish the prognosis in patients who encounter
      the rare complications such as subdural haematomas. In conclusion, CT and MRI can
      provide a highly accurate diagnosis in these patients, allowing a preliminary
      assessment of the prognosis, particularly regarding the enlarged subarachnoid
      space limits and the "cortical vein" sign which can predict a further
      complication. These results are obtained with the same examination performed in a
      standard CT or MRI study of the brain and no injection of contrast medium is
      needed. 

PMID- 24750716
TI  - The impact of lumen size and microvascular resistance on Fourier-domain optical
      coherence tomography (FD-OCT) coronary measurements.

PMID- 24750717
TI  - Visualizing anatomical evidences on atrioventricular conduction system for TAVI.
AB  - Visualizing the anatomy of the atrioventricular (AV) conduction axis
      substantiates that there is remarkable inter-individual variation at the macro-
      and microscopic levels, and that the atrioventricular bundle and left bundle
      branch are located more anteriorly, distally, and cranially and much closer to
      the aortic root complex than previously thought. The AV conduction system may
      therefore be compromised during implantation of a transcatheter aortic valve
      prosthesis, which may account for the relatively high incidence of new cardiac
      conduction abnormalities when conventional prosthetic valves are used. The design
      of the newer JenaValve(r) may afford advantages over more conventional valves by
      avoiding the high-risk implantation area and the potential for coronary ostia
      obstruction. 

PMID- 24750718
TI  - Prevalence and relative risk factors of atrial fibrillation in male coal miners
      in North China.

PMID- 24750719
TI  - Elevated red cell distribution width level is associated with oxidative stress
      and inflammation in a canine model of rapid atrial pacing.

PMID- 24750720
TI  - A new memetic pattern based algorithm to diagnose/exclude coronary artery
      disease.

PMID- 24750721
TI  - Does the return to work have a negative impact on the lifestyle of cardiovascular
      patients? Comments on the ICAROS results.

PMID- 24750722
TI  - Vogt-Koyanagi-Harada disease has specific ophthalmoscopic findings which will
      make easy the diagnosis.

PMID- 24750723
TI  - Association of chemokine receptor gene variants with HIV-1 genotype predicted
      tropism.
AB  - OBJECTIVES: As a switch from chemokine (C-C motif) receptor 5 [CCR5 (R5)] to
      chemokine (C-X-C motif) receptor 4 [CXCR4 (X4)] HIV-1 tropism is associated with
      symptomatic and AIDS stages of infection, while chemokine receptor gene variants
      modify the tempo of HIV disease progression, we aimed to analyse the association
      between pretreatment HIV-1 tropism and chemokine polymorphisms known to restrict
      disease progression. METHODS: V3 genotype tropism prediction was performed in a
      group of 221 treatment-naive patients, with subsequent CCR5 Delta32 (rs333), CCR2
      V64I (rs1799864), CCR5 promoter (-627 C/T; rs1799988) and CX3CR1 V249I
      (rs3732378) genotyping performed in 206 patients. Alleles with a protective
      effect were assigned positive values while risk alleles were assigned negative
      values to calculate genetic scores. chi(2) tests, Mann-Whitney U-tests and
      logistic and linear regression models were used for statistical analyses.
      RESULTS: R5 tropism was found in 85.5% of patients (n = 189) using a false
      positive rate (FPR) of 5.75% and in 72.8% of patients (n = 161) using an FPR of
      10%. A higher frequency of the 5.75% FPR predicted R5 tropism was associated with
      the CX3CR1 A allele (P = 0.027). Lower additive genetic scores were associated
      with an increased frequency of 5.75% FPR predicted R5 tropism (P = 0.0059), with
      the trend confirmed by logistic regression [odds ratio (OR) 0.5819; 95%
      confidence interval (CI) 0.3457-0.9795; P = 0.0416]. Viral load tended to
      increase with decreasing genetic score in the logistic regression analysis (slope
      = -0.127 +/- 0.076; P = 0.095; r(2)  = 0.161). CONCLUSIONS: The CX3CR1 A allele
      and lower genetic scores may restrict the switch of HIV-1 tropism from R5 to X4.
      This effect may be associated with the amount of co-receptor on the cell surface.
      Chemokine receptor gene polymorphisms influence both disease progression and
      tropism variability.

PMID- 24750724
TI  - Quaternized chitosan-layered silicate intercalated composites based nanofibrous
      mats and their antibacterial activity.
AB  - Quaternized chitosan (HTCC)-organic rectorite (OREC) intercalated composites
      based electrospun nanofibrous mats were fabricated from HTCC-OREC/polyvinyl
      alcohol (PVA) solutions for the first time. The morphology, intercalated
      structure, and antibacterial activity of the as-spun mats were investigated. The
      transmission electron microscopy images taken from HTCC-OREC composites showed
      that HTCC chains were inside the OREC interlayer. Scanning electron microscopy
      results verified that more typical fibrous structure would be generated by adding
      OREC. Fourier transform infrared spectra and energy-dispersive X-ray spectroscopy
      results indicated that OREC existed in the HTCC-OREC/PVA nanofibrous mats. The
      intercalation structure in nanofibrous mats was confirmed by X-ray diffraction
      results, which confirmed that HTCC and PVA chains could intercalate into the
      interlayer of OREC. The antibacterial activity of the electrospun mats was
      enhanced when the amount of the OREC increased. Therefore, the novel ternary
      nanofibrous mats could be used in the field of food packaging and biomedical
      applications. 

PMID- 24750725
TI  - Antitumor and antioxidant activities of levan and its derivative from the isolate
      Bacillus subtilis NRC1aza.
AB  - The novel levansucrase produced from Bacillus subtilis NRC1aza yielded two types
      of levan L1 and L2 with different molecular weights 85.23 kDa and 31.95 kDa,
      respectively. The levan identification was detected by paper chromatography and
      high-pressure liquid chromatography. The antioxidant activity of levan and their
      derivatives (SL1 and SL2) exhibited a strong free radical scavenging activity
      with DPPH. The antitumor activity of SL1 was tested against different human
      cancer cell lines. The cell death was explored mechanistically through evaluation
      of Apoptosis/necrosis ratio, DNA fragmentation, histone deacetylase activity,
      mitochondrial transmembrane potential (Deltapsim), cytochrome C release, total
      caspases, caspase-3, and caspase-9, and cell cycle. SL1 showed high selective
      cytotoxicity against HepG2 cells. SL1 led to DNA damaging and fragmentation that
      was associated with induced apoptosis via mitochondrial pathway, which initiated
      by the impairment of Deltapsim and then increased mitochondria, released
      cytochrome c, that in turn activated caspase-9 and caspase-3 and induced
      apoptosis.

PMID- 24750726
TI  - Benznidazole drug delivery by binary and multicomponent inclusion complexes using
      cyclodextrins and polymers.
AB  - Benznidazole (BNZ) is the drug of choice for Chagas disease treatment, which
      affects about 9.8 million people worldwide. It has low solubility and high
      toxicity. The present study aimed to develop and characterize inclusion complexes
      (IC) in binary systems (BS) with BNZ and randomly methylated-beta-cyclodextrin
      (RMbetaCD) and in ternary systems (TS) with BNZ, RMbetaCD and hydrophilic
      polymers. The results showed that the solid BS had a large increase in
      dissolution rate (Q>80%). For the solid IC obtained, the kneading method, in
      ratio of 1:0.17 (77.8% in 60 min), appeared to be the most suitable for the
      development of a solid oral pharmaceutical product, with possible industrial
      scale-up and low concentration of CD. The solid TS containing 0.1% of
      hydroxypropylmethylcellulose (HPMC) showed no significant advantages compared to
      the binary IC in solid state. The use of cyclodextrins proved to be a viable tool
      for effective, standardized and safe drug delivery.

PMID- 24750727
TI  - Alterations in cell-wall glycosyl linkage structure of Arabidopsis murus mutants.
AB  - Methylation (glycosyl-linkage) analyses of the cell walls from Arabidopsis
      (Arabidopsis thaliana L., Heynh.) murus mutants revealed variations in the
      linkage structure compared to wild type. Linkage analyses revealed new features
      for mutations whose defective gene has not been identified. For example, the low
      rhamnose mur8 mutant also shows deficiencies in 4-GalA linkages. No change in the
      2-Rha to 2,4-Rha ratio indicates the mutant had lower amounts of
      rhamnogalacturonan I, but no alteration in its fine structure. For all mur
      mutants, methylation analysis revealed that changes in other polysaccharides
      occur indirectly as a result of mutation. All mutants were resolved by Principal
      Components Analyses applied to normalized mole% values for the total set of
      linkage groups. The 'loadings' responsible for discrimination of mutant and wild
      type revealed variation in linkage groups otherwise difficult to discern and, in
      certain instances when the gene is known, resolved the specific deficiency from
      indirect effects altering other sugar linkage distributions. 

PMID- 24750728
TI  - Effect of co-solvent on the spinnability and properties of electrospun cellulose
      nanofiber.
AB  - The effects of the type and the concentration of the co-solvent on the
      spinnability during cellulose electrospinning and the properties of the fiber
      were studied using cellulose dissolved in ionic liquid and co-solvent (DMF or
      DMAc). The prepared solution was electrospun onto a wired collector and
      coagulated in ethanol. As the weight ratio of co-solvent against ionic liquid
      increased, the spinnability was improved with stable whipping and splaying
      motion. Regardless of the co-solvent type, the higher co-solvent concentration
      resulted in finer fiber diameter, better web uniformity, higher crystallinity and
      better thermal stability. Comparing to DMAc, DMF showed more significant
      influence on the fiber diameter and the crystallinity. 

PMID- 24750729
TI  - Biodegradation of PVP-CMC hydrogel film: a useful food packaging material.
AB  - Hydrogels can offer new opportunities for the design of efficient packaging
      materials with desirable properties (i.e. durability, biodegradability and
      mechanical strength). It is a promising and emerging concept, as most of the
      biopolymer based hydrogels are supposed to be biodegradable, they can be
      considered as alternative eco-friendly packaging materials. This article reports
      about synthetic (polyvinylpyrrolidone (PVP)) and biopolymer (carboxymethyl
      cellulose (CMC)) based a novel hydrogel film and its nature of biodegradability
      under controlled environmental condition. The dry hydrogel films were prepared by
      solution casting method and designated as 'PVP-CMC hydrogel films'. The hydrogel
      film containing PVP and CMC in a ratio of 20:80 shows best mechanical properties
      among all the test samples (i.e. 10:90, 20:80, 50:50, 80:20 and 90:10). Thus, PVP
      CMC hydrogel film of 20:80 was considered as a useful food packaging material and
      further experiments were carried out with this particular hydrogel film.
      Biodegradation of the PVP-CMC hydrogel films were studied in liquid state (Czapec
      Dox liquid medium+soil extracts) until 8 weeks. Variation in mechanical,
      viscoelastic properties and weight loss of the hydrogel films with time provide
      the direct evidence of biodegradation of the hydrogels. About 38% weight loss was
      observed within 8 weeks. FTIR spectra of the hydrogel films (before and after
      biodegradation) show shifts of the peaks and also change in the peak intensities,
      which refer to the physico-chemical change in the hydrogel structure and SEM
      views of the hydrogels show how internal structure of the PVP-CMC film changes in
      the course of biodegradation. 

PMID- 24750730
TI  - Synthesis of the ketimine of chitosan and 4,6-diacetylresorcinol, and study of
      the catalase-like activity of its copper chelate.
AB  - In this study, a new chitosan derivative (ketimine) was synthesized by
      condensation of chitosan with 4,6-diacetylresorcinol (DAR) at heterogeneous
      medium. The ketimine derivative of chitosan (DAR-chitosan) was characterized by
      elemental (C, H, N), spectral (DR-UV-vis and FT-IR spectroscopy), structural
      (powder XRD), and morphological (SEM) analyses. The degree of substitution (DS)
      of DAR-chitosan was evaluated by elemental analysis and (13)C CP-MAS NMR
      spectroscopy and found to be around 12%. The copper (II) metal complex of DAR
      chitosan was prepared and characterized by FT-IR, DR-UV-vis and inductively
      coupled plasma-atomic emission spectroscopy (ICP-AES). Thermal behaviors of the
      synthesized compounds were investigated by DSC and TG-DTG-DTA analysis. The
      catalytic activity of copper (II) complex of chitosan derivative (DAR-chitosan
      Cu) was investigated on hydrogen peroxide decomposition. The copper chelate
      showed high efficiency (over 80%) towards the decomposition of hydrogen peroxide
      as heterogeneous catalyst. 

PMID- 24750731
TI  - Cellular uptake and cytotoxicity of chitosan-caseinophosphopeptides nanocomplexes
      loaded with epigallocatechin gallate.
AB  - Epigallocatechin gallate (EGCG) was successfully encapsulated in novel
      nanocomplexes assembled from bioactive peptides, caseinophosphopeptides (CPPs),
      and chitosan (CS), a natural cationic polymer. Their particle sizes and surface
      charges were determined to be in the range of 150.0+/-4.3 nm and 32.2+/-3.3 mV
      respectively. Crosslinking between the -NH3+ groups of CS with the -P=O- and -COO
      groups of CPP, as well as the hydrogen bonding were confirmed from the FTIR
      results. Atomic force microscopy (AFM) images showed that EGCG loaded CS-CPP
      nanocomplexes were spherical in shape. Maintaining the surface charge as high as
      +32.2 mV, crosslinking CS with peptides reduced the cytotoxicity of CS
      nanoparticles. In addition, cellular internalization of EGCG-loaded CS-CPP
      nanoparticles was confirmed from green fluorescence inside the Caco-2 cells. The
      process of nanoparticle uptake was dose and time dependent in the range of time
      and concentration studied. Furthermore, the intestinal permeability of EGCG using
      Caco-2 monolayer was enhanced significantly as delivered by nanoparticles, which
      indicated the promising elevation of EGCG bioavailability.

PMID- 24750732
TI  - Chemical modification and antioxidant activities of polysaccharide from mushroom
      Inonotus obliquus.
AB  - Chemical modification polysaccharides exerted potent biological property which
      was related to the physicochemical properties. In the present study,
      polysaccharides from Inonotus obliquus were modified by suflation, acetylation
      and carboxymethylation. The physicochemical and antioxidant properties of I.
      obliquus polysaccharide (IOPS) and its derivatives were comparatively
      investigated by chemical methods, gas chromatography, size exclusion
      chromatography, scanning electron micrograph, infrared spectra and circular
      dichroism spectra, and ferric reducing power assay and lipid peroxidation
      inhibition assay, respectively. Results showed that physicochemical and
      antioxidant properties of IOPS were differed each other after the chemical
      modification of suflation, acetylation and carboxymethylation. Among the three
      derivatives, acetylationed polysaccharide (Ac-IOPS) resulted in lower molecular
      weight distribution, lower intrinsic viscosity, a hyperbranched conformation,
      higher antioxidant abilities on ferric-reducing power and lipid peroxidation
      inhibition activity compared with the native polysaccharide IOPS. Ac-IOPS might
      be explored as a novel potential antioxidant for human consumption. 

PMID- 24750733
TI  - RGD-conjugated UV-crosslinked chitosan scaffolds inoculated with mesenchymal stem
      cells for bone tissue engineering.
AB  - Biomimetic chitosan scaffolds were prepared using two types of chitosan
      derivatives, one containing photoreactive azides for UV-crosslinking and the
      other tethered with RGD peptides. Mesenchymal stem cells (MSCs) isolated from rat
      bone marrow were cultured in the RGD-conjugated, UV-crosslinked chitosan
      scaffolds for bone tissue engineering. RGD-incorporation to the chitosan-based
      scaffolds increased the cell contents from 2.4*10(4) to 3.8*10(4) cells/scaffold
      and 3.4*10(4) to 5.1*10(4) cells/scaffold after 1 and 10 days of culture,
      respectively. Furthermore, osteogenic differentiation of MSCs, indicated by ALP
      activity and expression of Runx2 and osteocalcin genes, was enhanced on the RGD
      conjugated surface compared with the unmodified surfaces. After 14 days of
      osteogenic culture, calcium deposition in the RGD-conjugated scaffolds (711 nmol
      Ca/scaffold) was significantly higher than the control (390 nmol Ca/scaffold).
      The results demonstrate a potential application of RGD-immobilized, crosslinked
      chitosan scaffolds for bone tissue engineering applications.

PMID- 24750734
TI  - Synthesis and characterization of dithiocarbamate chitosan derivatives with
      enhanced antifungal activity.
AB  - In this study, ammonium dithiocarbamate chitosan (ADTCCS) and triethylene diamine
      dithiocarbamate chitosan (TEDADTCCS) derivatives were obtained respectively by
      mixing chitosan with carbon disulfide and ammonia (triethylenediamine). Their
      structures were confirmed by FT-IR, 1H NMR, XRD, DSC, SEM, and elemental
      analysis. Antifungal properties of them against the plant pathogenic fungi
      Fusarium oxysporum and Alternaria porri were investigated at concentrations
      ranged from 31.25 to 500 mg/L. The dithiocarbamate chitosan derivatives had
      enhanced antifungal activity compared with chitosan. Particularly, they showed
      obvious inhibitory effect on Fusarium oxysporum. At 500 mg/L, TEDADTCCS inhibited
      growth of F. oxysporum at 60.4%, stronger than polyoxin and triadimefon whose
      antifungal indexes were found to be 25.3% and 37.7%. The chitosan derivatives
      described here deserve further study for use in crop protection.

PMID- 24750735
TI  - Degradation of kappa-carrageenan by hydrolysis with commercial alpha-amylase.
AB  - kappa-Carrageenan was degraded by hydrolysis using commercial alpha-amylase (4000
      U/mg). The hydrolysis process was monitored by the intrinsic viscosity [eta] of
      the hydrolysates. Factors affecting the enzymatic hydrolysis of carrageenan were
      investigated, and the optimum hydrolysis conditions were as follows: duration, 4
      h; pH, 7.5; temperature, 50 degrees C; and amount of commercial alpha-amylase, 40
      mg of the mixture containing 5 g kappa-Carrageenan. Under the optimized
      conditions, minimum intrinsic viscosity (12.31) was obtained. The dextrose
      equivalent value of the resulting products was 20.41, indicating that the average
      degree of polymerization was approximately equal to 5.0. The hydrolysates were
      filtered, concentrated to ~15% (w/v), and precipitated with 6 volumes of ethanol;
      the precipitates were then freeze-dried to yield a white, water-soluble powder.
      The carrageenan-derived oligosaccharide content of the product and the yield were
      96.5% and 92.6% (w/w), respectively.

PMID- 24750736
TI  - Structure feature and antitumor activity of a novel polysaccharide isolated from
      Lactarius deliciosus Gray.
AB  - A novel heteropolysaccharide was isolated from the fruiting bodies of Lactarius
      deliciosus Gray through DEAE-cellulose column and Sephadex G-100 column. The L.
      deliciosus Gray polysaccharide (LDG-A) had a molecular weight of 1.1*10(4) Da and
      was mainly composed of L-mannose and D-xylose (L-Man and D-Xyl) which ratio was
      3:1. As a precondition to understand the bioactivity, structural feature of L.
      deliciosus Gray polysaccharide (LDG-A) were investigated by a combination of
      total hydrolysis, methylation analysis, gas chromatography-mass spectrometry (GC
      MS), scanning electron microscope (SEM), infrared (IR) spectra, nuclear magnetic
      resonance (NMR) spectroscopy and dynamical analysis of the atomic force
      microscope (AFM) studies. The results indicated that L. deliciosus Gray
      polysaccharide (LDG-A) had a backbone of 1,6-disubstituted-alpha-L-mannopyranose
      which branched at O-2 and the branches were mainly composed of a ->3)-alpha-D
      xylopyranose residue. LDG-A exhibited significant anti-tumor activates in vivo.
      L. deliciosus Gray may be one ideal sources of antitumor development.

PMID- 24750737
TI  - N-hexanoyl, N-octanoyl and N-decanoyl chitosans: Binding affinity, cell uptake,
      and transfection.
AB  - Low transfection efficiency of chitosan limits its use as a non-viral vector for
      practical purposes. This study was designed to investigate the effect of fatty
      acyl chain length on physicochemical properties, pDNA binding affinity, cell
      uptake, and in vitro transfection efficiency of N-acyl chitosan (NAC). NAC
      polymers were synthesized by carbodiimide mediated coupling reaction of chitosan
      with n-hexanoic, n-octanoic, and n-decanoic acid, respectively. These NAC
      polymers effectively condensed pDNA resulting in the size range of 220-342 nm
      with net positive charge. NAC polymers also showed good pDNA binding capacity,
      high protection of pDNA from nuclease degradation and excellent biocompatibility.
      Transfection efficiency of chitosan, in HEK 293 cells, was enhanced 15-25-fold
      after coupling with fatty acid and increased with a decrease in fatty acyl chain
      length of NAC. Thus, the present study demonstrates that the NAC polymers hold
      great potential as novel non-viral gene delivery vector.

PMID- 24750738
TI  - Green synthesis of hyaluronan fibers with silver nanoparticles.
AB  - The application of green chemistry in the nano-science and technology is very
      important in the area of the preparation of various materials. In this work, an
      eco-friendly chemical method was successfully used for the preparation of
      hyaluronan fibers containing silver nanoparticles (AgNPs). Thus, hyaluronic acid
      (HA) was dissolved in an aqueous solution of sodium hydroxide to prepare a
      transparent solution, which was used for the preparation of fibers by a wet
      spinning technique. Consequently, silver nanoparticles inside the fiber were
      prepared. Different parameters affecting the preparation of final product, such
      as concentration of silver nitrate, hyaluronan fiber concentration, time and
      temperature of the reaction, pH of the reaction mixture, were studied. AgNPs were
      confirmed by transmission electron microscopy (TEM), X-ray diffraction (XRD), two
      dimensional X-ray scattering (2D SWAXS), UV/Vis spectroscopy, inductively coupled
      plasma optical emission spectrometry (ICP OES) and scan electron microscopy
      (SEM). Mechanical properties of prepared fibers were also measured. 

PMID- 24750739
TI  - Effect of lignin content on a GH11 endoxylanase acting on glucuronoarabinoxylan
      lignin nanocomposites.
AB  - The effects of lignin content on the activity and action pattern of GH11
      endoxylanase from Thermobacillus xylanilyticus were investigated using in vitro
      reconstituted non-covalent glucuronoarabinoxylan-model lignin (GAX-DHP)
      nanocomposites. Four types of nanocomposites were prepared, each displaying
      different lignin contents. Variations in the DHP (model lignin) polymerization
      process were induced by increasing the coniferyl alcohol concentration.
      Examination of the morphology of the nanocomposites revealed globular particles
      enrobed in a matrix. The size of these particles increased in line with the
      lignin concentration. Physicochemical characterization of the in vitro
      reconstituted GAX-DHPs strongly suggested that increased particle size is
      directly related to the solubility and reactivity of coniferyl alcohol, as
      reflected by changes in the amount of beta-O-4 linkages. Evaluation of the impact
      of the GH11 endoxylanase on the GAX-DHP nanocomposites revealed a negative
      correlation between the proportion and organization patterns of DHP in the
      nanocomposites and enzyme activity. 

PMID- 24750740
TI  - Estimation of resistance of starch/polyvinyl alcohol blends to permeation by
      organic solvents.
AB  - The chemical resistance of chlorinated hydrocarbons in starch/polyvinyl alcohol
      (PVA) blends has been investigated using a permeation cell with an in-cell solid
      phase microextraction (SPME) sampling device. The chlorinated hydrocarbon with a
      large molecule size or lower polarity was found to be less permeable through the
      starch/PVA blends. The tensile strength and chemical resistance of chlorinated
      hydrocarbons decreased with an increase in the starch content of blends. For the
      starch/PVA blends, the solubility of chlorinated hydrocarbons was inversely
      proportional to their molecular weight, molar volume and log Kow. The diffusion
      coefficients and solubility of permeants were proportional to the content of
      starch in the starch/PVA blends. It is plausible that the blends will be inclined
      to the starch characteristics as the plasticizer (i.e. glycerin) disrupts the
      rigidity arrangements of the starch and PVA. The present work provides
      information on the extent of organic compound permeation through starch/PVA
      blends for the practical application.

PMID- 24750741
TI  - Original stimuli-sensitive polysaccharide derivatives/N-isopropylacrylamide
      hydrogels. Role of polysaccharide backbone.
AB  - This article compares the properties of a novel class of unsaturated Xanthan and
      Gellan derivatives/N-isopropylacrylamide stimuli-responsive hydrogels synthesized
      by free radical polymerization. Xanthan and Gellan Gum were partially
      functionalized by esterification with maleic anhydride under various conditions.
      By copolymerization of these maleate polysaccharides with a N-isopropylacrylamide
      known temperature sensitive precursor, water-swollen hydrogels with
      interpenetrating polymer networks (IPN) were obtained. The hydrogels were
      characterized for their temperature and pH-responsive behaviour by equilibrium
      swelling experiments and differential scanning calorimetry. The investigation of
      these materials also includes solid-state (13)CP/MAS NMR and elemental analysis
      of the nitrogen content. Morphology was visualized by scanning electron
      microscopy. Depending upon composition and the nature of the base-polysaccharide,
      the hydrogels showed different response rates to the external changes of
      temperature as well as pH. By changing the feed composition ratio of precursors
      and crosslinking agent (beta-cyclodextrin acrylate or N,N'-methylenebisacrylamide
      respectively) the phase transition temperature (lower critical solution
      temperature) could also be adjusted near to the body temperature for biomedical
      and biotechnological applications. The role of the rigidity and the charge
      density of the polysaccharide chain, its ability to form hydrogen bonding on
      these properties are more particularly considered. 

PMID- 24750742
TI  - Antioxidant activity and hepatoprotective effect of a polysaccharide from Bei
      Chaihu (Bupleurum chinense DC).
AB  - Chinese medicine plays a pivotal role in hepatoprotective treatment. In the
      present study, a water-soluble polysaccharide fraction (WBCP) was fractioned from
      the roots of Bupleurum chinense and purified by DEAE-cellulose and Surperdex 200
      HR chromatography. The physicochemical properties, antioxidative and
      hepatoprotective activities of WBCP were evaluated in a rat model of hepatic
      injury caused by d-galactosamine (GalN). Hepatoprotective effect was evaluated by
      measuring aspartate transaminase (AST), alanine transaminase (ALT), alkaline
      phosphatase (ALP) and lactate dehydrogenase (LDH) activities in the plasma of
      mice. Antioxidant activity was evaluated by measuring biochemical parameters in
      the mouse liver homogenate, such as glutathione reductase (GR), gamma
      glutamylcysteine synthetase (GCS), glutathione S-transferase (GST) and superoxide
      dismutase (SOD) activities, as well as glutathione (GSH) and thiobarbituric acid
      reactive substances (TBARS) levels. The results showed the oral administration of
      WBCP could significantly reduce the activity of AST, ALT, ALP and LDH, indicating
      that WBCP possesses hepatoprotective activity. Furthermore, there was general a
      statistically significant increase in the activities of GSH, GR, GCS, GST and
      SOD, and a loss in TBARS in the liver of WBCP-treated group compared with the
      control group. In addition, the elevated levels of pro-inflammatory cytokine
      tumour necrosis factor-alpha (TNF-alpha) in the serum of the experimental animals
      was significantly returned by WBCP treatment at the dose of 400 mg/kg. These
      results clearly demonstrated that WBCP possess promising hepatoprotective effects
      against GalN-induced liver damage, which may be mediated through augmentation of
      antioxidant defenses.

PMID- 24750743
TI  - In vitro evaluation of mucoadhesion and permeation enhancement of polymeric
      amphiphilic nanoparticles.
AB  - Oleoyl-carboxymethy-chitosan (OCMCS) nanoparticles based on chitosan with various
      molecular weights were prepared using coacervation process, which demonstrated
      particle size of 150-350 nm, zeta potential of 10-20 mV, and high encapsulation
      efficiency of fluorescein isothiocyanate dextran (FD4). OCMCS nanoparticles were
      found to be adsorbed onto the excised carp intestinal mucosa, the extent of
      adsorption increased with increasing chitosan molecular weight. In comparison to
      FD4 solution, OCMCS nanoparticles promoted FD4 transport through excised carp
      intestinal mucosa by 3.26-6.52 folds, which were observed via fluorescence
      microscope. The OCMCS nanoparticulate systems that interacted with the Caco-2
      cells decreased the transepithelial electric resistance (TEER) and induced
      increasing the apparent permeability coefficient (Papp) of FD4 by 3.61-6.32
      folds. Cytotoxicity studies in Caco-2 monolayers verified the safety of the
      delivery system. The improvement of mucoadhesive ability and permeability enable
      the OCMCS nanosystems suitable carriers for the intestinal absorption of protein
      drugs.

PMID- 24750744
TI  - Cordyceps militaris polysaccharides can enhance the immunity and antioxidation
      activity in immunosuppressed mice.
AB  - To evaluate the immune activation and reactive oxygen species scavenging activity
      of Cordyceps militaris polysaccharides (CMP) in vivo, 90 male BALB/c mice were
      randomly divided into six groups. The mice in the three experimental groups were
      given cyclophosphamide at 80 mg/kg/d via intraperitoneal injection and 17.5, 35,
      or 70 mg/kg body weight CMP via gavage. The lymphocyte proliferation, phagocytic
      index, and biochemical parameters were measured. The results show that the
      administration of CMP was able to overcome the CY-induced immunosuppression,
      significantly increased the spleen and thymus indices, and enhanced the spleen
      lymphocyte activity and macrophage function. CMP can also improve the
      antioxidation activity in immunosuppressed mice, significantly increase the
      superoxidase dismutase, catalase, and glutathione peroxidase levels and the total
      antioxidant capacity, and decrease the malondialdehyde levels in vivo.

PMID- 24750745
TI  - Green synthesis of silver nanoparticles by a novel method: comparative study of
      their properties.
AB  - This study presents a novel green method using starch for the synthesis of silver
      nanoparticles (AgNPs). In this method, the fungal supernatant was added to a
      mixture of starch and silver nitrate solutions. The characteristics of AgNPs
      synthesized by three independent processes-a modified polysaccharide method, a
      microbial method, and our novel method-were compared. Dynamic light scattering
      (DLS) analysis revealed that the average sizes of AgNPs synthesized by the
      microbial method, the modified polysaccharide method, and our novel method were
      84, 20, and 15 nm, respectively. The most stable AgNPs were generated by our
      novel method. The X-ray diffraction (XRD) spectrum of the products from the novel
      method showed that these AgNPs have high crystallinity. Fourier-transform
      infrared spectroscopy (FTIR) spectra demonstrated that the functional groups
      present in the products prepared by the novel method are a combination of the
      functional groups present in the AgNPs synthesized by the other two methods.

PMID- 24750746
TI  - Post-crosslinking modification of thermoplastic starch/PVA blend films by using
      sodium hexametaphosphate.
AB  - Thermoplastic starch (TPS)/poly (vinyl alcohol) (PVA) blend films were post
      treated by crosslinking through soaking the films in sodium carbonate aqueous
      solution and sodium hexametaphosphate aqueous solution sequentially and then
      heating. The effects of the concentrations of the sodium carbonate aqueous
      solution and the sodium hexametaphosphate aqueous solution, soaking time, heating
      temperature and time on the properties of the TPS/PVA blend films were
      investigated. It was found that the crosslinking modification significantly
      reduced the moisture sensitivity of the TPS/PVA blend films, i.e., lowered the
      equilibrium moisture content of the blend films, increased the tensile strength
      and Young's modulus but decreased the elongation at break of the blend films. The
      described method could be used for post-treating TPS/PVA based products to
      optimize their properties. 

PMID- 24750747
TI  - Swelling and mechanical properties of superabsorbent hydrogels based on Tara
      gum/acrylic acid synthesized by gamma radiation.
AB  - The main objective is to develop a new superabsorbent system especially for using
      in diaper applications. In this study, hydrogels based on Tara gum/acrylic acid
      (TG/AAc) were prepared by gamma irradiation, in the presence of N,N'
      methylenebisacrylamide (MBAAm) as a crosslinking agent. The polymeric networks
      formed were characterized by FT-IR and evaluated by swelling studies as a
      function of MBAAm concentration, temperature and nature of the swelling medium.
      The swelling kinetics of the hydrogels was studied in terms of the diffusion
      exponent "n". The results showed that the water diffusion into hydrogels is a non
      Fickian type. Mechanical measurements (stress-strain) curves of hydrogels were
      evaluated to calculate the shear modulus values and the average molecular weight
      between crosslinks (Mc). Moreover, the absorption under load at 37 degrees C of
      water and urea aqueous solutions (as a major component of urine) by TG/AAc
      hydrogels was determined. 

PMID- 24750748
TI  - Synthesis and characteristics of chitin and chitosan with the (2-hydroxy-3
      trimethylammonium)propyl functionality, and evaluation of their antioxidant
      activity in vitro.
AB  - Quaternary amino groups were introduced into chitin and chitosan to obtain O-(2
      hydroxy-3-trimethylammonium)propyl chitin (OHT-chitin) and N-(2-hydroxy-3
      trimethylammonium)propyl chitosan (NHT-chitosan). They were characterized by FTIR
      spectra, and GPC. The molecular weight Mw of OHT-chitin and NHT-chitosan were
      8986 and 9723 with polydispersity of 1.01 and 1.0 2, respectively. Their
      antioxidant activities in vitro were further studied. It was found that beta
      carotene-linoleic acid values of OHT-chitin and NHT-chitosan at 0.8 mg/mL were up
      to 91% and 96%, while that of chitosan was 40%. Based on photobleaching of
      alpha,alpha-diphenyl-beta-picrylhydrazyl (DPPH) at 326 nm, the DPPH inhibitory
      activity of OHT-chitin and NHT-chitosan was 30.9% and 31.9% at 5 mg/mL, whereas
      chitosan only gave 4.8%. It was also exhibited that OHT-chitin and NHT-chitosan
      had better antioxidant activity than chitosan according to the reducing power as
      well as H2O2 scavenging activity.

PMID- 24750749
TI  - Inclusion complex of astaxanthin with hydroxypropyl-beta-cyclodextrin: UV, FTIR,
      1H NMR and molecular modeling studies.
AB  - The structure and complex mode of the inclusion complex of astaxanthin with
      hydroxypropyl-beta-cyclodextrin (HPCD) were investigated by UV, FTIR, 1H NMR and
      molecular modeling test. UV, FTIR and 1H NMR results indicated that the hexatomic
      ring of the astaxanthin molecules were partly included into the HPCD cavities.
      The implementation of molecular modeling test confirmed that the complexation
      could reduce the energy of the system and the complex of 2:1 host-guest
      stoichiometry had the lowest DeltaE value, -30.57 kcal/mol, two hexatomic ring
      ends of one astaxanthin molecule inserted into two HPCD cavities respectively,
      and that should be the most predominant configuration.

PMID- 24750750
TI  - Structural characterization and properties of konjac glucomannan/curdlan blend
      films.
AB  - A series of novel edible blend films of konjac glucomannan (KGM) and curdlan were
      prepared by a solvent-casting technique with different blending ratios of the two
      polymers. The Fourier transform infrared spectroscopy (FT-IR), X-ray diffraction
      (XRD), differential scanning calorimetry (DSC), scanning electron microscopy
      (SEM), etc. were used to characterize the change of structure and properties of
      blend films. The results showed that the strong intermolecular hydrogen bonds
      took place between KGM and curdlan. And the interaction of the blend film was
      much greater than that of the others when the KGM content in the blend films was
      around 70 wt% (KC7), resulting in excellent miscibility. The conclusion of the
      electron tensile testing analysis indicated that the blend film KC7 showed the
      maximum tensile strength (42.93+/-1.92 MPa). In addition, the blend films
      displayed excellent moisture barrier properties, which had a potential
      application in the food field.

PMID- 24750751
TI  - Composites of thermoplastic starch and nanoclays produced by extrusion and
      thermopressing.
AB  - The aim of this study was to produce thermoplastic starch (TPS) films and to
      enhance their properties by reinforcing them with hydrophilic and hydrophobic
      nanoclays. TPS films were prepared by extrusion and thermopressing, and their
      crystallinity, water vapor permeability (WVP), and mechanical properties were
      studied. The hydrophilic nanoclay lowered the material WVP due to the formation
      of an intercalated composite. The hydrophobic nanoclays increased the rigidity of
      the films but did not alter the tensile strength. The blending of nanoclays with
      thermoplastic starch modifies the mechanical properties and WVP, and these
      changes are strongly associated with the dispersion of nanoclay in the polymer
      matrix. The dispersion, in turn, depends on the compatibility of the matrix and
      the nanoclay in terms of the hygroscopicity and the concentration in which the
      nanoclay is used. The addition of nanoclays to starch-based films is a promising
      way to enhance them for industrial manufacture. 

PMID- 24750752
TI  - Inhibition of angiogenesis by chitooligosaccharides with specific degrees of
      acetylation and polymerization.
AB  - Chitooligosaccharides (CHOS) inhibit angiogenesis and may be used in the
      treatment of cancer tumors. We have studied the effect of the fraction of
      acetylation (FA) and the degree of polymerization (DP) on CHOS anti-angiogenic
      activity. We tested enzymatically produced CHOS-mixtures with FA0.15, FA0.3 and
      FA0.6, and DP<=12 in initial experiments with chorioallantoic membranes. All of
      the samples reduced the formation of new blood vessels, CHOS with FA0.3 giving
      the best effect. Single-DP fractions from the FA0.3 sample purified by size
      exclusion chromatography (DP3-DP12) were then tested for inhibition of migration
      of human endothelial cells, which is an important element of the angiogenesis
      process. All of the fractions inhibited migration, meaning that, within the DP
      area tested in this study, FA is more important than DP for the effect.
      Generally, the results reveal that DP3-DP12 CHOS have considerable potential as
      anti-angiogenic compounds. 

PMID- 24750753
TI  - Further analysis of the structure and immunological activity of an RG-I type
      pectin from Panax ginseng.
AB  - In this paper, we further analysed the structure of a type I rhamnogalacturonan
      (RG-I) pectin (WGPA-2-RG) fractionated from ginseng polysaccharides. Methylation
      and periodate oxidation analyses showed that WGPA-2-RG has a backbone consisting
      of alternating rhamnose (Rha) and galacturonic acid (GalA) residues and side
      chains consisting of type II arabinogalactan (AG-II). Partial acidic hydrolysis
      for 6h completely removed arabinose (Ara), partial galactose (Gal), but little
      GalA and Rha. During partial hydrolysis, the molecular weight of WGPA-2-RG
      decreased smoothly, suggesting that the Ara and cleavable Gal residues exist on
      the surface of the molecule, while GalA and Rha residues exist in the core of the
      molecule. The bioactivity assay showed that the arabinogalactan side chains of
      WGPA-2-RG are essential structures for stimulating NO secretion and lymphocyte
      proliferation. However, removal of the Ara and Gal residues through hydrolysis
      did not appreciably affect the ability of WGPA-2-RG to enhance macrophage
      phagocytosis. 

PMID- 24750754
TI  - Studies on the tosylation of cellulose in mixtures of ionic liquids and a co
      solvent.
AB  - The tosylation of cellulose in ionic liquids (ILs) was studied. Due to the
      beneficial effect of different co-solvents, the reaction could be performed at 25
      degrees C without the need of heating (in order to reduce viscosity) or cooling
      (in order to prevent side reactions). The effects of reaction parameters, such as
      time, molar ratio, and type of base, on the degree of substitution (DS) with
      tosyl- and chloro-deoxy groups as well as on the molecular weight were evaluated.
      Products with a DStosyl<=1.14 and DSCl<=0.16 were obtained and characterized by
      means of NMR- and FT-IR spectroscopy in order to evaluate their purity and
      distribution of functional groups within the modified anhydroglucose unit (AGU).
      Tosylation of cellulose in mixtures of IL and a co-solvent was found to result in
      predominant substitution at the primary hydroxyl group. Size exclusion
      chromatography (SEC) revealed only a moderate degradation of the polymer backbone
      at a reaction time of 4-8h. Finally, the nucleophilic displacement (SN) of tosyl-
      and chloro-deoxy groups by azide as well as recycling of the ILs was studied. 

PMID- 24750755
TI  - Radiation synthesis and characterization of hyaluronan capped gold nanoparticles.
AB  - Gold nanoparticles (AuNPs) with diameter from 4 to 10nm, capping by hyaluronan
      (HA) were synthesized using a gamma-irradiation method. The maximum absorption
      wavelengths at 517-525 nm of colloidal AuNPs/HA solutions were measured by UV-vis
      spectroscopy. The size and size distribution of AuNPs were determined from TEM
      images. The influence of various factors on the size of AuNPs particularly the
      concentration of Au3+ and HA, and dose rate were also investigated. Results
      indicated that higher dose rate and HA concentration favor smaller sizes of AuNPs
      whereas the size increases with Au3+ concentration. The colloidal AuNPs/HA
      solution was fairly stable more than 6 months under storage at ambient condition.
      The AuNPs stabilized by biocompatible HA with the size less than 10nm as prepared
      can potentially be applied in biomedicines and cosmetics.

PMID- 24750756
TI  - Interaction study in homogeneous collagen/chondroitin sulfate blends by two
      dimensional infrared spectroscopy.
AB  - The neutral homogeneous collagen/chondroitin sulfate (Col/CS) blends were
      prepared when using 0.25 mol/L NaCl to stabilize the blends. Composition
      dependent Fourier transform-infrared (FTIR) spectra were analyzed by generalized
      two-dimensional (2D) correlation spectroscopy to investigate the conformational
      changes of collagen and the specific interactions between collagen and CS. When
      adding CS to the collagen solution, C-H bending vibration of collagen varies
      firstly, then collagen skeleton, and finally the specific interactions between
      collagen and CS. The Col/CS ratios influence the kinds of specific interactions.
      Only hydroxyl groups of CS interact with CO group of collagen owing to the charge
      shielding effect of NaCl when the CS content is less than 50 wt%. Besides
      hydrogen bond, the electrostatic interactions between ionized carboxyl group or
      sulfate group of CS and E-amino group of lysine or guanidine group of arginine
      appear when the CS content is more than 50 wt%.

PMID- 24750757
TI  - Highly flexible magnetic composite aerogels prepared by using cellulose
      nanofibril networks as templates.
AB  - Nanostructured cellulose nanofibrils can form ductile or tough networks that are
      suitable templates for the creation of materials with functional properties. In
      this work, a facile method has been developed for the preparation of magnetic
      hybrid cellulose aerogels. The preparation processes followed by two steps,
      firstly, preparation of cellulose hydrogel films from LiOH/urea solvent, then
      CoFe2O4 nanoparticles were synthesized in the porous structured cellulose
      scaffolds. After being freeze-dried, CoFe2O4/cellulose magnetic aerogels were
      obtained. The porosity of the composite aerogels ranged from 78 to 52% with pore
      size distribution in a few tens of nanometers. The internal specific surface
      areas were around 300-320 m2/g, and the densities were in the range of 0.25-0.39
      g/cm3. The hybrid aerogels showed improved mechanical strength, superparamagnetic
      properties. Unlike solvent-swollen gels and ferrogels, the magnetic composite
      aerogels were lightweight, flexibility, high porosity and with large specific
      surface area and could be expected to be used in many fields.

PMID- 24750758
TI  - Durable press finishing of cotton fabrics with polyamino carboxylic acids.
AB  - In this study, a polyamino carboxylic acid was synthesized by reaction of a
      commercial polyvinylamine and bromoacetic acid. The reaction product was used for
      crosslinking of cotton fabric by a pad-dry-cure process. Crosslinking of the
      finished cotton occurred via the formation of ester bonds between the carboxylic
      groups of the polyamino carboxylic acid and the hydroxyl groups of cellulose.
      Ester bonds were confirmed by appearance of the corresponding absorbance at 1730
      cm(-1) in the FTIR spectrum of the finished cotton. The created durable press
      effect on the finished cotton with polyamino carboxylic acid was evaluated by
      measuring the wrinkle recovery angle (WRA). Impact of this finishing agent on the
      physical properties of the cotton was studied by evaluating the tensile strength
      and whiteness index, and softness of the finished cotton. The easy care effect
      was durable against laundering. Softness, whiteness, and tensile strength of the
      finished cotton have not changed significantly.

PMID- 24750759
TI  - Solubilization of haloperidol by acyclic succinoglycan oligosaccharides.
AB  - The isolated succinoglycan octasaccharide dimers isolated from Sinorhizobium
      meliloti 1021 have unique acyclic structures, displaying amphipathic properties
      against water. Thus, their potential usage as solubilizers of various water
      insoluble drugs through non-covalent complexation are possible. In this study, we
      examined the solubility of a poorly water-soluble drug, haloperidol, in the
      presence of the acyclic form of succinoglycan dimers, and demonstrated that its
      solubility was increased up to 87 fold, Interestingly, the level of its
      solubility was even 7-10 fold higher than that achieved with beta cyclodextrin or
      its derivatives that are cyclic forms, which is possibly due to the molecular
      flexibility of the acyclic structure of the dimers as well as the hydrophobic
      nature. Analyses of the stoichiometry and the stability constants for each
      complex were performed using phase solubility method, respectively. Additional
      analyses were also performed to confirm the formation of succinoglycan-drug
      complexes. Furthermore hypothetical 3-dimesional conformation of the complex was
      estimated through molecular docking simulations. Upon cytotoxicity test with a
      human cell line, the succinoglycan dimers displayed little effect up to 1000 MUM,
      suggesting their potential usage to improve solubility and bioavailability of
      poorly soluble therapeutic agents.

PMID- 24750760
TI  - Physicochemical properties of rhizome starch from a traditional Chinese medicinal
      plant of Anemone altaica.
AB  - This study investigated the physicochemical properties of rhizome starch of A.
      altaica for the first time. The results were compared to those obtained from two
      common starches (potato and rice). The rhizome had a starch content of 49.8%.
      Isolated starch granules were mostly oval in shape with a central Maltese cross
      and an average long axis of 6.25 MUm. The starch contained 35.5% amylose and had
      lower gelatinization and pasting temperatures than rice and potato starches and a
      swelling power comparable to potato. Altaica starch had high breakdown and
      setback viscosities. X-ray diffraction revealed B-type starch with relative
      degree of crystallinity of 17.5%. Starch possessed a high susceptibility to
      hydrolysis by acid, porcine pancreatic alpha-amylase and Aspergillus niger
      amyloglucosidase when compared with potato and rice starches.

PMID- 24750761
TI  - Multi-responsive carboxymethyl polysaccharide crosslinked hydrogels containing
      Jeffamine side-chains.
AB  - The paper studies the synthesis and characterization of crosslinked
      carboxymethylpullulan hydrogels containing Jeffamine (Jef) (M-600 and M-2005)
      [polyoxyalkyleneamines (polyethylene oxide, polypropylene oxide)] units as side
      chains, linked through amide bonds. These hydrogels present pH sensitive
      properties due to the presence of anionic functional groups and thermoassociative
      properties due to the Jeff units. They were characterized through FTIR spectra,
      swelling behavior in various media, at various pH or temperatures, retention of
      hydrophobic molecules, to appreciate their pH-sensitive and thermoassociative
      (multi-responsive) properties. The interaction with biomolecules as proteins:
      lysozyme, BSA and antioxidants as: lutein and alpha-tocopherol was studied, to
      estimate some potential application domains of these new synthesized hydrogels. 

PMID- 24750762
TI  - A novel xyloglucan film-based biosensor for toxicity assessment of ricin in
      castor seed meal.
AB  - Oil from the seed of the castor plant (Ricinus communis L.) is an important
      commodity for a number of industries, ranging from pharmaceuticals to renewable
      energy resources. However, the seed and subsequent seed meal contain ricin
      (RCA60), a potent cytotoxin, making it an unusable product for animal feed. In
      order to investigate the efficiency of reducing the toxicity of the seed meal, a
      biosensor is proposed by exploring the lectin-carbohydrate binding. A gold
      electrode was assembled with a film of Xyloglucan (XG) extracted from Hymenaea
      courbaril L. The analytical response to RCA60 was obtained using a polyclonal
      antibody against RCA60 conjugated to peroxidase. The current responses were
      generated by reaction with H2O2 and amplified with hydroquinone as chemical
      mediator. Voltammetric studies showed that the XG film was tightly bound to the
      gold electrode. This biosensor allows discriminate lectins in native and
      denatured forms. The limit of detection of native RCA60 was 2.1 MUg mL(-1). This
      proposed biosensor showed to be a potential and accurate method for toxicity
      assessment of the ricin in castor seed meal by simple polysaccharide film
      electrode strategy.

PMID- 24750763
TI  - Water adsorption isotherms of carboxymethyl cellulose, guar, locust bean,
      tragacanth and xanthan gums.
AB  - Water adsorption isotherms of carboxymethyl cellulose (CMC), guar gum (GG),
      locust bean gum (LBG), tragacanth gum (TG) and xanthan gum (XG) were determined
      at different temperatures (20, 35, 50, and 65 degrees C) using a gravimetric
      method. Several saturated salt solutions were selected to obtain different water
      activities in the range from 0.09 to 0.91. Water adsorption isotherms of tested
      hydrocolloids were classified like type II isotherms. In all cases, equilibrium
      moisture content decreased with increasing temperature at each water activity
      value. Three-parameter Guggenheim-Anderson-de Boer (GAB) model was employed to
      fit the experimental data in the water activity range and statistical analysis
      indicated that this model gave satisfactory results. CMC and GG were the most and
      the least hygroscopic gums, respectively. Sorption heats decreased with
      increasing moisture content. Monolayer moisture content evaluated with GAB model
      was consistent with equilibrium conditions of maximum stability calculated from
      thermodynamic analysis of net integral entropy. Values of equilibrium relative
      humidity at 20 degrees C are proposed to storage adequately the tested gums. 

PMID- 24750764
TI  - Molecular characteristics and anti-inflammatory activity of the fucoidan
      extracted from Ecklonia cava.
AB  - Enzymatic extraction has been successfully used for extracting numerous
      biologically active compounds from a wide variety of seaweeds. In this study, we
      found that enzymatic extraction of the fucoidan from Ecklonia cava may be more
      advantageous than water extraction. Therefore, we studied the E. cava fucoidans
      extracted by the enzymatic extraction technique and used ion-exchange
      chromatography to determine their molecular characteristics and anti-inflammatory
      activities. The crude and fractionated fucoidans (F1, F2, and F3) consisted
      mostly of carbohydrates (47.1-57.1%), uronic acids (9.0-15.8%), and sulfates
      (16.5-39.1%), as well as varying levels of proteins (1.3-8.7%). The
      monosaccharide levels significantly differed, and the composition included fucose
      (53.1-77.9%) and galactose (10.1-32.8%), with a small amount of rhamnose (2.3
      4.5%), xylose (4.0-8.2%), and glucose (0.8-2.2%). These fucoidans contained one
      or two subfractions with an average molecular weight (Mw) ranging from 18 to
      359*10(3)g/mol. These fucoidans significantly inhibited NO production in
      lipopolysaccharide (LPS)-induced Raw 264.7 macrophage cells by down-regulating
      the expression of iNOS, COX-2, and pro-inflammatory cytokines such as TNF-alpha,
      IL-6, and IL-1beta. Thus, the present results suggest that E. cava fucoidan may
      be a potentially useful therapeutic approach for various inflammatory diseases. 

PMID- 24750765
TI  - Enhanced hydrogenolysis conversion of cellulose to C2-C3 polyols via alkaline
      pretreatment.
AB  - Alkaline pretreatment was applied to enhance hydrogenolysis conversion of
      cellulose to C2-C3 polyols. The alkali cellulose was obtained by treating
      cellulose with different concentration of NaOH solution. The scanning electron
      microscopy (SEM) and X-ray diffraction (XRD) results indicate that the cleavage
      of cellulose chains occurs and the amorphous part is increased after alkaline
      treatment, which means the alkali cellulose has more accessible structure.
      Moreover, the absorbed NaOH crystal in alkali cellulose could make the further
      reaction perform in weak basic condition. When hydrogenolysis of alkali cellulose
      over Ru/C was conducted at 433 K, 59.23% of the substrate was converted with 1,2
      propanediol and ethylene glycol as main products, whereas the corresponding
      conversion rate of untreated cellulose was 25.05% and no C2-C3 polyols were
      detected. These preliminary results suggested the advantages of activating the
      cellulose by alkaline pretreatment and potentials for efficient conversion of
      cellulose. Finally the plausible mechanism was also discussed.

PMID- 24750766
TI  - Altering the growth conditions of Gluconacetobacter xylinus to maximize the yield
      of bacterial cellulose.
AB  - An extensive matrix of different growth conditions including media, incubation
      time, inoculum volume, surface area and media volume were investigated in order
      to maximize the yield of bacterial cellulose produced by Gluconacetobacter
      xylinus, which will be used as reinforcement material to produce fully
      biodegradable composites. Crystallinity was shown to be controllable depending on
      the media and conditions employed. Samples with significant difference in
      crystallinity in a range from 50% to 95% were produced. Through experimental
      design, the yield of cellulose was maximized; primarily this involved reactor
      surface area design, optimized media and the use of mannitol being the highest
      cellulose-producing carbon source. Increasing the volume of the media did achieve
      a higher cellulose yield, however this increase was not found to be cost or time
      effective. 

PMID- 24750767
TI  - Water-soluble beta-cyclodextrin grafted with chitosan and its inclusion complex
      as a mucoadhesive eugenol carrier.
AB  - Inclusion complex between water-soluble betaCD-grafted chitosan derivatives (QCD
      g-CS) and eugenol (EG) was investigated as a new type of mucoadhesive drug
      carrier. The QCD-g-CSs were synthesized with various betaCD moieties ranging from
      5 to 23%. Spontaneous inclusion complex of these derivatives and EG were found
      and confirmed by FTIR and simulation study. Self-aggregated formations of QCD-g
      CS were found, according to fluorescence and TEM studies, where the formations
      were preferable for QCD11g-CS and QCD5-g-CS. EG can be included in both betaCD
      hydrophobic cavity and hydrophobic core of QCD-g-CS self-aggregates, resulting in
      varying entrapment efficiencies. Degree of QCD substitution on QCD-g-CS plays an
      important role on their physical properties, due to steric hindrance. The QCD11-g
      CS showed excellent mucoadhesion, compared to the QCD5-g-CS and QCD23-g-CS.
      Moreover, the inclusion complex between QCD-g-CS and EG tend to express higher
      antimicrobial activities against Candida albicans, Streptococcus oralis and
      Streptococcus mutans, than the native QCD-g-CS. 

PMID- 24750768
TI  - Nano-hybrid carboxymethyl-hexanoyl chitosan modified with (3
      aminopropyl)triethoxysilane for camptothecin delivery.
AB  - Silane-modified amphiphilic chitosan was synthesized by anchoring a silane
      coupling agent, (3-aminopropyl)triethoxysilane, to a novel amphiphilic
      carboxymethyl-hexanoyl chitosan (CHC). The chemical structure of this new organic
      inorganic hybrid molecule was characterized by FTIR and 13C-, 29Si-nuclear
      magnetic resonance, while the structural evolution was examined using scanning
      electron microscopy (SEM), transmission electron microscopy (TEM), X-ray
      diffraction (XRD), and dynamic light scattering (DLS). Experimental results
      indicated a self-assembly behaviour of molecules into nanoparticles with a stable
      polygonal geometry, consisting of ordered silane layers of 6 nm in thickness. The
      self-assembly property was found to be influenced by chemical composition and
      concentration of silane incorporated, while the size can be varied by the amount
      of anchored silane. It was also demonstrated that such vesicle exhibited
      excellent cytocompatibility and cellular internalization capability in ARPE-19
      cell line, and presented well-controlled encapsulation and release profiles for
      (S)-(+)-camptothecin. These unique properties render it as a potential drug
      delivery nanosystem.

PMID- 24750769
TI  - Hydration properties of regioselectively etherified celluloses monitored by 2H
      and 13C solid-state MAS NMR spectroscopy.
AB  - The hydration properties of 2,3-O-hydroxypropylcellulose (HPC) and 2,3-O
      hydroxyethylcellulose (HEC) were analyzed by multi-nuclear solid-state MAS NMR
      spectroscopy. By 13C single-pulse (SP) MAS and cross-polarization (CP) MAS NMR,
      differences between the immobile regions and all parts of the polysaccharides
      were detected as a function of hydration. Complementary information about the
      water environments was observed by 2H MAS NMR. By this approach it was
      demonstrated that side chains in 2,3-O-HPC and 2,3-O-HEC were easier to hydrate
      than the cellulose backbone. Furthermore the motion of water was more restricted
      (slower) in 2,3-O-HPC than in 2,3-O-HEC. For both polysaccharides the hydration
      could be explained by a two-step process: in step one increased ordering of the
      immobile regions occurs after which the entire polymer is hydrated in step two.

PMID- 24750770
TI  - Poly(acrylic acid)/poly(ethylene glycol) adduct for attaining multifunctional
      cellulosic fabrics.
AB  - Aqueous polymerization of partially neutralized acrylic acid (AA) along with
      polyethylene glycol (PEG-600) at AA/PEG-600 mass ratio 3/1 using ammonium
      persulfate as initiator under proper conditions results in formation of PAA/PEG
      600 adduct. The structure of the adduct was confirmed by FT-IR spectra. The
      potential applications of the prepared adduct in: sizing, durable hand building
      of cotton cellulose, as well as in functional finishing of cellulose containing
      fabrics, i.e. cotton, viscose and cotton/polyester, with Ag- or TiO2
      nanoparticles were investigated. The modified substrates using the prepared
      adduct showed a remarkable improvement in their sizing, hand building and/or
      functional properties, i.e. antibacterial, anti-UV, and self cleaning, in
      addition to durability to wash. TEM images of the prepared nano-particles, SEM
      images of the untreated and treated substrates, as well as EDX spectra to analyze
      the surface elemental compositions were examined. The tentative mechanisms were
      also suggested. 

PMID- 24750771
TI  - Microanalysis of oligosaccharide HS203 in beagle dog plasma by postcolumn
      fluorescence derivatization method.
AB  - A rapid and sensitive postcolumn fluorescence derivatization method was developed
      for microanalysis of antidiabetic oligosaccharide HS203 in beagle dog plasma.
      After plasma protein was removed by a simple and fast ultrafiltration method,
      chromatographic separation was performed on an Asahipak GS-320 HQ column with a
      mobile phase of 50 mmol/L phosphate buffer (pH 6.7) and acetonitrile (83/17,
      v/v). The column effluent was monitored by fluorescence detection at 249 nm
      (excitation) and 435 nm (emission) using guanidine hydrochloride as a postcolumn
      derivatizing reagent. A satisfactory resolution of the analyte was achieved and
      the limit of detection was found to be 4 ng (more sensitive than silver staining
      of HS203 in polyacrylamide gel electrophoresis). The method described above was
      successfully applied to a pharmacokinetic study of HS203 and to monitor blood
      glucose level simultaneously in beagle dog. It is also possible to be applied for
      microanalysis of other oligosaccharides in biological samples.

PMID- 24750772
TI  - pH-sensitive sodium alginate hydrogels for riboflavin controlled release.
AB  - Sodium alginate (SA) grafted with polyglycidyl methacrylate hydrogels (PGMA-g-SA)
      was prepared as pH sensitive drug delivery matrices for riboflavin (RF). The
      hydrogel copolymer matrices were compared with calcium alginate (CA) beads for
      swelling, degradation, entrapment efficiency and in vitro release of RF. The
      structure, surface morphology of the CA beads and the prepared hydrogels as well
      as the chemical stability of the encapsulated drug were characterized by FT-IR
      and SEM, respectively. The results demonstrate that the optimal formulation was
      achieved with PGMA-g-SA proportion of (0.75 mol/1 g) and loaded RF 0.03 g. It has
      been observed that the in vitro release study of RF from this formulation was
      superior to the other ones and was able to maintain the release for ~3 and 4 days
      for the simulated intestinal fluid (SIF) and simulated gastric fluid (SGF),
      respectively. In general, it has been shown that, GMA grafted onto SA enhanced
      drug entrapment efficiency, decreased swelling and degradation behaviors of the
      carrier. In addition, it slowed and controlled the release of RF from the PGMA-g
      SA hydrogel compared with pure SA beads crosslinked with Ca2+ ions alone, which
      thereby provides a facile and effective method to improve the drug delivery
      systems.

PMID- 24750773
TI  - Influence of hydroxypropylmethylcellulose addition and homogenization conditions
      on properties and ageing of corn starch based films.
AB  - Edible films based on corn starch, hydroxypropyl methylcellulose (HPMC) and their
      mixtures were prepared by using two different procedures to homogenize the film
      forming dispersions (rotor-stator and rotor-stator plus microfluidizer). The
      influence of both HPMC-starch ratio and the homogenization method on the
      structural, optical, tensile and barrier properties of the films was analysed.
      The ageing of the films was also studied by characterizing them after 5 weeks'
      storage. Starch re-crystallization in newly prepared and stored films was
      analysed by means of X-ray diffraction. HPMC-corn starch films showed phase
      separation of polymers, which was enhanced when microfluidization was applied to
      the film forming dispersion. Nevertheless, HPMC addition inhibited starch re
      crystallization during storage, giving rise to more flexible films at the end of
      the period. Water barrier properties of starch films were hardly affected by the
      addition of HPMC, although oxygen permeability increased due to its poorer oxygen
      barrier properties. 

PMID- 24750774
TI  - Nanocomposites based on plasticized starch and rectorite clay: structure and
      properties.
AB  - Sodium rectorite clay (REC) was attached to cationic guar gum (CGG) using a
      cationic-exchange reaction to obtain CGG modified-REC (CREC). It was found that
      CGG appeared on the surface of REC's layered structure and represented about
      30.1% wt. in CREC. REC and CREC were, respectively, used as fillers in a
      plasticized starch (PS) matrix to prepare PS/REC and PS/CREC composites using the
      casting process. Rapid Visco Analyser and scanning electron microscopy revealed
      that an interaction existed between the REC (or CREC) filler and the matrix. Both
      REC and CREC had obvious reinforcing effects on the matrix. Compared to the neat
      matrix, REC or CREC improved the thermal stability of the composites. By
      increasing the filler content from 0 to 10 wt%, water vapor permeability (WVP)
      values of PS/REC composites obviously decreased, while WVP values of PS/CREC
      composites decreased slightly.

PMID- 24750775
TI  - Characterization of antioxidant polysaccharides from Auricularia auricular using
      microwave-assisted extraction.
AB  - Influence of microwave-assisted extraction (MAE) to the characterization and
      corresponding antioxidant activity of polysaccharides from Auricularia auricula
      (AAP) was determined. According to gas chromatography-mass spectrometry, high
      performance size exclusion chromatography, Fourier transform infrared
      spectroscopy, partial acid hydrolysis, periodic acid oxidation, Smith
      degradation, methylation analysis and atomic force microscopy, AAP was a
      heteropolysaccharide (composed of glucose, galactose, mannose, arabinose and
      rhamnose at the molar ratio of 37.53:1:4.32:0.93:0.91) with the molecular weight
      of 2.77*10(4) Da, observed as a spherical lump, and the backbone of AAP was
      mainly composed by glucose with (1->3) linked. Moreover, AAP exhibited
      significant in vitro antioxidant activity in scavenging free radicals (ABTS,
      DPPH, superoxide and hydroxyl radicals), in lipid peroxidation and reducing power
      assays. The present result suggested that AAP by MAE had low molecular weight and
      remarkable antioxidant capability.

PMID- 24750776
TI  - An exopolysaccharide from Trichoderma pseudokoningii and its apoptotic activity
      on human leukemia K562 cells.
AB  - In this study, a novel exopolysaccharide (EPS) was isolated from the fermentation
      broth of Trichoderma pseudokoningii and its anticancer activities on human
      leukemia K562 cells were studied. EPS could significantly inhibited K562 cells
      proliferation in a time- and concentration-dependent manner. Meanwhile,
      characteristic of apoptosis, including apoptotic morphological features and the
      apoptosis rate were obtained. Sequentially, the dissipation of mitochondrial
      membrane potential, increase production of Reactive oxygen species (ROS),
      enhancement of the concentration of intracellular, up-regulation of Bax and p53
      mRNA, down-regulation of Bcl-2 mRNA were also detected. The results indicate that
      the EPS could induce of K562 cells apoptosis, primarily in involved the
      mitochondrial pathways. The present studies suggest that EPS could be a new
      potential adjuvant chemotherapeutic and chemo preventive agent against human
      leukemia. 

PMID- 24750777
TI  - Preparation of low-molecular-weight hyaluronic acid by ozone treatment.
AB  - Recently, low-molecular-weight hyaluronic acid has been reported to have novel
      features, such as free radical scavenging activities, antioxidant activities,
      promotion of excisional wound healing, etc. In the present work, degradation of
      native hyaluronic acid by ozone treatment was performed for preparation of low
      molecular-weight hyaluronic acid. The molecular weight of native hyaluronic acid
      was reduced from 1535 to 87 kDa for 120 min at 40 degrees C. The rate of
      reduction of molecular weight was 94.33%. The FT-IR, 13C NMR, and UV-vis spectra
      suggested that there was no obvious modification of chemical structure of low
      molecular-weight hyaluronic acid. The use of degradation of native hyaluronic
      acid by ozone treatment can be a useful alternative for production of low
      molecular-weight hyaluronic acid.

PMID- 24750778
TI  - Electrophysiological phenotypes of MeCP2 A140V mutant mouse model.
AB  - AIMS: MeCP2 gene mutations are associated with Rett syndrome and X-linked mental
      retardation (XLMR), diseases characterized by abnormal brain development and
      function. Recently, we created a novel MeCP2 A140V mutation mouse model that
      exhibited abnormalities of cell packing density and dendritic branching
      consistent with that seen in Rett syndrome patients as well as other MeCP2 mutant
      mouse models. Therefore, we hypothesized that some deficits of neuronal and
      synaptic functions might also be present in the A140V mutant model. METHODS:
      Here, we tested our hypothesis in hippocampal slices using electrophysiological
      recordings. RESULTS: We found that in young A140V mutant mice (3- to 4-week-old),
      hippocampal CA1 pyramidal neurons exhibited more positive resting membrane
      potential, increased action potential (AP) firing frequency induced by injection
      of depolarizing current, wider AP duration, and smaller after hyperpolarization
      potential compared to neurons prepared from age-matched wild-type mice,
      suggesting a neuronal hyperexcitation. At the synaptic level, A140V mutant
      neurons exhibited a reduced frequency of spontaneous IPSCs (inhibitory
      postsynaptic potentials) and an enhanced probability of evoked glutamate release,
      both suggesting neuronal hyperexcitation. However, hippocampal CA1 long-term
      potentiation was not significantly different between A140V and WT mice. In adult
      mice (11- to 13-month-old), in addition to neuronal hyperexcitation, we also
      found significant deficits of both short-term and long-term potentiation of CA3
      CA1 synapses in A140V mice compared to WT mice. CONCLUSIONS: These results
      clearly illustrate the age-dependent abnormalities of neuronal and synaptic
      function in the MeCP2 A140V mutant mouse model, which provides new insights into
      the understanding of the pathogenesis of Rett syndrome.

PMID- 24750779
TI  - Hepatic progenitor cells in liver regeneration: current advances and clinical
      perspectives.
AB  - When there is a massive loss of hepatocytes and/or an inhibition in the
      proliferative capacity of the mature hepatocytes, activation of a dormant cell
      population of resident hepatic progenitor cells (HPCs) occurs. Depending on the
      type of liver damage HPCs generate new hepatocytes and biliary cells to
      repopulate the liver placing them as potential candidates for cell therapy in
      human liver failure. Liver injury specific mechanisms through which HPCs
      differentiate towards mature epithelial cell types are recently become
      understood. Such new insights will enable us not only to direct HPCs behaviour
      for therapeutic purposes, but also to develop clinically feasible methods for in
      vivo differentiation of other stem cell types towards functional hepatocytes.
      This review aimed to provide the current improved knowledge of the role of HPCs
      niche and its signals in directing the behaviour and fate of HPCs and to
      translate this basic knowledge of HPCs activation/differentiation into its
      clinical applications. 

PMID- 24750780
TI  - The cost-benefit of using soft silicone multilayered foam dressings to prevent
      sacral and heel pressure ulcers in trauma and critically ill patients: a within
      trial analysis of the Border Trial.
AB  - Little is known about the cost-benefit of soft silicone foam dressings in
      pressure ulcer (PU) prevention among critically ill patients in the emergency
      department (ED) and intensive care unit (ICU). A randomised controlled trial to
      assess the efficacy of soft silicone foam dressings in preventing sacral and heel
      PUs was undertaken among 440 critically ill patients in an acute care hospital.
      Participants were randomly allocated either to an intervention group with
      prophylactic dressings applied to the sacrum and heels in the ED and changed
      every 3 days in the ICU or to a control group with standard PU prevention care
      provided during their ED and ICU stay. The results showed a significant reduction
      of PU incidence rates in the intervention group (P = 0.001). The intervention
      cost was estimated to be AU$36.61 per person based on an intention-to-treat
      analysis, but this was offset by lower downstream costs associated with PU
      treatment (AU$1103.52). Therefore, the average net cost of the intervention was
      lower than that of the control (AU$70.82 versus AU$144.56). We conclude that the
      use of soft silicone multilayered foam dressings to prevent sacral and heel PUs
      among critically ill patients results in cost savings in the acute care hospital.

PMID- 24750781
TI  - WUSCHEL-related Homeobox genes in Populus tomentosa: diversified expression
      patterns and a functional similarity in adventitious root formation.
AB  - BACKGROUND: WUSCHEL (WUS)-related homeobox (WOX) protein family members play
      important roles in the maintenance and proliferation of the stem cell niche in
      the shoot apical meristem (SAM), root apical meristem (RAM), and cambium (CAM).
      Although the roles of some WOXs in meristematic cell regulation have been well
      studied in annual plants such as Arabidopsis and rice, the expression and
      function of WOX members in woody plant poplars has not been systematically
      investigated. Here, we present the identification and comprehensive analysis of
      the expression and function of WOXs in Populus tomentosa. RESULTS: A genome-wide
      survey identified 18 WOX encoding sequences in the sequenced genome of Populus
      trichocarpa (PtrWOXs). Phylogenetic and gene structure analysis revealed that
      these 18 PtrWOXs fall into modern/WUS, intermediate, and ancient clades, but that
      the WOX genes in P. trichocarpa may have expanded differently from the WOX genes
      in Arabidopsis. In the P. trichocarpa genome, no WOX members could be closely
      classified as AtWOX3, AtWOX6, AtWOX7, AtWOX10, and AtWOX14, but there were two
      copies of WOX genes that could be classified as PtrWUS, PtrWOX2, PtrWOX4,
      PtrWOX5, PtrWOX8/9, and PtrWOX11/12, and three copies of WOX genes that could be
      classified as PtrWOX1 and PtrWOX13. The use of primers specific for each PtrWOX
      gene allowed the identification and cloning of 18 WOX genes from P. tomentosa
      (PtoWOXs), a poplar species physiologically close to P. trichocarpa. It was found
      that PtoWOXs and PtrWOXs shared very high amino acid sequence identity, and that
      PtoWOXs could be classified identically to PtrWOXs. We revealed that the
      expression patterns of some PtoWOXs were different to their Arabidopsis
      counterparts. When PtoWOX5a and PtoWOX11/12a, as well as PtoWUSa and PtoWOX4a
      were ectopically expressed in transgenic hybrid poplars, the regeneration of
      adventitious root (AR) was promoted, indicating a functional similarity of these
      four WOXs in AR regeneration. CONCLUSIONS: This is the first attempt towards a
      systematical analysis of the function of WOXs in P. tomentosa. A diversified
      expression, yet functional similarity of PtoWOXs in AR regeneration is revealed.
      Our findings provide useful information for further elucidation of the functions
      and mechanisms of WOXs in the development of poplars.

PMID- 24750782
TI  - Outbreaks of Kingella kingae infections in daycare facilities.
AB  - During the past decade, transmission of the bacterium Kingella kingae has caused
      clusters of serious infections, including osteomyelitis, septic arthritis,
      bacteremia, endocarditis, and meningitis, among children in daycare centers in
      the United States, France, and Israel. These events have been characterized by
      high attack rates of disease and prevalence of the invasive strain among
      asymptomatic classmates of the respective index patients, suggesting that the
      causative organisms benefitted from enhanced colonization fitness, high
      transmissibility, and high virulence. After prophylactic antibacterial drugs were
      administered to close contacts of infected children, no further cases of disease
      were detected in the facilities, although test results showed that some children
      still carried the bacterium. Increased awareness of this public health problem
      and use of improved culture methods and sensitive nucleic acid amplification
      assays for detecting infected children and respiratory carriers are needed to
      identify and adequately investigate outbreaks of K. kingae disease. 

PMID- 24750783
TI  - von Willebrand disease and aging: an evolving phenotype.
AB  - BACKGROUND: Because the number of elderly von Willebrand disease (VWD) patients
      is increasing, the pathophysiology of aging in VWD has become increasingly
      relevant. OBJECTIVES: To assess age-related changes in von Willebrand factor
      (VWF) and factor VIII (FVIII) levels and to compare age-related differences in
      bleeding phenotype between elderly VWD patients and those < 65 years. We also
      studied co-morbidity in elderly patients. PATIENTS/METHODS: We included VWD
      patients with VWF levels <= 30 U dL(-1) in the nationwide cross-sectional
      'Willebrand in the Netherlands' (WiN-) study. Patients reported bleeding episodes
      and treatment of VWD in the year preceding inclusion and during life. This was
      compared between VWD patients older (n = 71) and younger (16-64 years, n = 593)
      than 65 years. In elderly patients, age-related changes in VWF and FVIII levels
      were studied longitudinally by including all historically measured levels. All
      medical records were examined for co-morbidity. RESULTS: In elderly type 1
      patients, a decade age increase was associated with a 3.5 U dL(-1) (95% CI, -0.6
      to 7.6) VWF:Ag increase and 7.1 U dL(-1) (95% CI, 0.7 to 13.4) FVIII:C increase.
      This increase was not observed in elderly type 2 patients. Elderly type 2
      patients reported significantly more bleeding symptoms in the year preceding
      inclusion than younger patients (16/27, 59% vs. 87/221, 39%; P = 0.048), which
      was not observed in type 1 VWD. CONCLUSIONS: von Willebrand factor parameters and
      bleeding phenotype evolve with increasing age in VWD. VWF and FVIII levels
      increase with age in type 1 patients with no mitigation in bleeding phenotype. In
      type 2 patients VWF parameters do not increase with age and in these patients
      aging is accompanied by increased bleeding.

PMID- 24750784
TI  - Heterogeneity of rectus femoris muscle architectural adaptations after two
      different 14-week resistance training programmes.
AB  - PURPOSE: This study aimed to determine the architectural changes of rectus
      femoris muscle at distinctive sites of the thigh length after two different 14
      week resistance training programmes. METHODS: Thirty-five untrained men were
      randomly allocated into three different groups: conventional resistance training
      (n = 12), isokinetic training (n = 12) and control (n = 11). Rectus femoris cross
      sectional area, thickness and fascicle angle at two specific thigh sites (30% and
      50% of the length) were assessed before and after 14 weeks of unilateral knee
      extension exercise or control. The isometric peak torque of the knee extensors
      was estimated as a muscle strength index. RESULTS: Conventional (30% = 47.4%
      versus 50% = 14.4%) and isokinetic (30% = 31.8% versus 50% = 11.4%) training
      induced significant increases on thickness at both rectus femoris sites. While
      conventional training resulted in substantial increments on cross-sectional area
      (30% = 62.1%, 50% = 19.5%), isokinetic training provoked a significant increase
      only at the distal site (50% = 64.7%). The isometric peak torque increased (22.4
      and 29.6%, for conventional and isokinetic groups, respectively) after training
      independently of the training mode, although no significant changes were observed
      for any dependent variable in the control group. CONCLUSIONS: In general, the
      training modes resulted in similar changes on rectus femoris architecture,
      whereas their magnitude depended on the thigh site.

PMID- 24750785
TI  - Role of transportation in spread of porcine epidemic diarrhea virus infection,
      United States.
AB  - After porcine epidemic diarrhea virus (PEDV) was detected in the United States in
      2013, we tested environmental samples from trailers in which pigs had been
      transported. PEDV was found in 5.2% of trailers not contaminated at arrival, ,
      suggesting that the transport process is a source of transmission if adequate
      hygiene measures are not implemented. 

PMID- 24750786
TI  - Glioblastoma stem cells: a new target for metformin and arsenic trioxide.
AB  - The high malignancy of glioblastoma has been recently attributed to the presence,
      within the tumor, of glioblastoma stem cells (GSC) poorly responsive to chemo-
      and radiotherapy. Here, the potential employment of metformin and arsenic
      trioxide (ATO) in glioblastoma therapy is discussed focusing on their effects on
      GSC. Metformin exerts anticancer effects by primarily blocking the pivotal
      LKB1/AMPK/mTOR/S6K1 pathway-dependent cell growth, induces selective lethal
      effects on GSC by impairing the GSC-initiating spherogenesis and inhibits the
      proliferation of CD133+ cells, while having a low or null effect on
      differentiated glioblastoma cells and normal human stem cells. Metformin and ATO
      induce autophagy and apoptosis in glioma cells by inhibiting and stimulating the
      PI3K/Akt and the mitogen-activated protein kinase pathways, respectively. Both
      drugs promote differentiation of GSC into non-tumorigenic cells. In this regard,
      metformin acts via activation of the AMPK-FOXO3 axis, whereas ATO blocks the
      interleukin 6-induced promotion of STAT3 phosphorylation. Blood-brain barrier,
      easily crossed by metformin but not by ATO, undergoes important glioblastoma
      induced alterations that increase its permeability, thus allowing ATO to
      distribute more into the glioblastoma bulk than in the normal brain parenchyma. A
      prompt clinical assessment of metformin and ATO in glioblastoma patients would
      represent a valid attempt to improve their survival. 

PMID- 24750787
TI  - Interrelationship between IL-3 and mast cells.
AB  - It is well established that mast cells, which are found in the tissues in the
      proximity of small blood vessels and post-capillary venules, play a key role in
      the early phase of IgE-mediated allergic reactions. A greatly expanded
      understanding of the biology of IL-3 has emerged since the early 1980s. IL-3 is a
      specific factor that stimulates the growth of hematopoietic stem and progenitor
      cells of a variety of lineages and can promote the proliferation of certain
      classes of lymphocytes distinct from those that are dependent on IL-2. IL-3 has
      been identified among the most important cytokines for regulation of mast cell
      growth and differentiation, migration and effector function activities of many
      hematopoietic cells. IL-3 termed multi colony-stimulating-factor (multi-CSF) or
      mast cell growth factor (MCGF) is a haematopoietic growth factor which stimulates
      the formation of colonies for erythroid, megakaryocytic, granulocytic and
      monocytic lineages. It is predominantly produced by activated T cells, natural
      killer (NK) cells and mast cells and supports the growth-promoting effects of SCF
      on mast cell precursors. IL-3 causes severe hypersensivity reactions and plays a
      pivotal role in exacerbating the inflammatory response in vivo. Here we report
      the interrelationship between IL-3 and mast cells. 

PMID- 24750789
TI  - The innate immunity receptor TIR8/SIGIRR is expressed in the early developmental
      stages of chicken embryos.
AB  - The orphan receptor TIR8, also known as SIGIRR (Single Immunoglobulin IL-1R
      Related molecule), belongs to the IL-1R/TLR (TIR) superfamily and plays an
      important role in the inflammatory responses. The signaling pathways of the
      receptors belonging to the TIR family are tightly regulated by both extracellular
      and intracellular mechanisms. TIR8 does not activate the transcription factors
      NFkB (nuclear factor kB) and IRF3 (interferon regulatory factor 3), although it
      negatively modulates the inflammatory responses. It acts as an antagonist for the
      IL-1 receptor family and triggers a negative pathway of the Toll-like/IL-1
      receptor system, crucial for dampening inflammation stimuli in the
      gastrointestinal (GI) tract and in other organs (e.g. lung and kidney). The
      recent findings of TLRs expression in ovary and embryos of different species
      (mammals and chickens) are very important for an understanding of reproductive
      physiology and transovarian pathogen transmission. TIR8 was well characterized in
      mouse, humans and in other mammalian species, but it is still poorly
      characterized in the chicken. When TIR8 expression was measured in selected
      organs of chicken embryos of both broiler and layer types at different time
      points a unique pattern of expression was observed. Interestingly, TIR8 was
      detected during the first stages of chicken development (day 1 of incubation),
      and reached a remarkable level of expression by day 10. We observed this receptor
      to be ubiquitously expressed in the kidney, GI tract, Bursa of Fabricius, with
      the highest expression levels in liver and kidney. This pattern was comparable to
      those observed in post-hatching chickens and in mammals examined to date. No
      expression differences were observed between the two different chicken breeds
      (layer- and broiler-type) in the first incubation period (8 days). Whereas in
      some organs starting from day 10, higher TIR8 expression was observed in broiler
      type compared to layer-type. These are the first findings concerning TIR8
      expression in developmental stages and therefore they are of comparative value. 

PMID- 24750788
TI  - Carbamate pesticide-induced apoptosis and necrosis in human natural killer cells.
AB  - We previously found that ziram, a carbamate fungicide, significantly induced
      apoptosis and necrosis in human NK-92MI, a natural killer cell line. To
      investigate whether other carbamate pesticides also induce apoptosis and necrosis
      in human natural killer cell, we conducted further experiments with NK-92CI, a
      human natural killer cell line using a more sensitive assay. NK-92CI cells were
      treated with ziram, thiram, maneb or carbaryl at 0.031-40 microM for 2-24 h in
      the present study. Apoptosis and necrosis were determined by FITC-Annexin-V/PI
      staining. To explore the mechanism of apoptosis, intracellular levels of active
      caspases 3 and mitochondrial cytochrome-c release were determined by flow
      cytometry. We found that ziram and thiram also induced apoptosis and necrosis in
      a time- and dose-dependent manner; however, maneb and carbaryl induced apoptosis
      and necrosis only at higher doses in NK-92CI cells. The strength of the apoptosis
      inducing effect differed among the pesticides, and the order was as follows:
      thiram > ziram greater than maneb greater than carbaryl. NK-92CI was more
      sensitive to ziram than NK-92MI. Moreover, ziram and thiram significantly
      increased the intracellular level of active caspase 3 in NK-92CI and caspase
      inhibitor significantly inhibited the apoptosis. Ziram and thiram significantly
      caused mitochondrial cytochrome-c release in NK-92CI. These findings indicate
      that carbamate pesticides can induce apoptosis in natural killer cells, and the
      apoptosis is mediated by both the caspase-cascade and mitochondrial cytochrome-c
      pathways. 

PMID- 24750790
TI  - Toll-like receptor 4 promotes control of Leishmania infantum infection through
      inducement of leishmanicidal activity in host macrophages: role of mitogen
      activated kinases.
AB  - Establishment of Leishmania infection inside macrophages requires deactivation of
      various signaling pathways that are dispensable for effective immune responses
      against the parasite. In the present study, we provide evidence that Leishmania
      infantum promastigotes attachment on the surface of peritoneal macrophages,
      internalization and transformation to amastigotes abrogated the activation of
      extracellular signal-regulated protein kinases (ERK) 1/2, p38 mitogen activated
      protein kinases (MAPK) and c-Jun NH2-terminal kinases (JNK) and the production of
      pro-inflammatory cytokines IL-12 and TNFalpha. Subsequent macrophage stimulation
      with lipopolysaccharide (LPS) during the first hours of exposure to parasite or
      infection resulted in restoration of MAPK phosphorylation. However, LPS-mediated
      MAPK activation required parasite internalization (uptake) since cytochalasin-D
      pretreated macrophages did not responded to LPS stimulation. IL-12, TNFalpha, and
      NO production was positively regulated with MAPK phosphorylation in contrast to
      nuclear factor-kappaB (NF-kB) which was MAPK independent. Specifically,
      inhibition of MAPK activation with specific inhibitors revealed that IL-12
      production required p38 MAPK activation, whereas TNFalpha and NO production
      required all three MAPK. The restoration of NO production resulted in decrease of
      infection rates. Hence, these results suggest that in contrast to phagocytosis of
      L. infantum promastigotes, establishment of infection does not desensitize
      macrophages to subsequent stimulation with LPS, resulting in parasite elimination
      through MAPK and NF-&#954;B activation and partial restoration of IL-12, TNFalpha
      and NO synthesis. 

PMID- 24750791
TI  - Iron supplementation in young iron-deficient females causes gastrointestinal
      redox imbalance: protective effect of a fermented nutraceutical.
AB  - The aim of this study was to assess whether the concomitant supplementation of
      certified fermented papaya preparation (FPP, ORI, Gifu, Japan) together with iron
      supplementation could beneficially affect lipid peroxidation either systemically
      and at a intraluminal gut level in women with low iron stores. Treatment
      compliance and iron absorption was assessed as well. Fifty-two non-pregnant,
      fertile, non-smokers, healthy women with iron deficiency were recruited. The
      women were given iron supplements (100 mg Fe/d as ferrous sulfate) to be taken
      daily for 12 weeks (group A). Group B patients were also supplemented with 6g/day
      of a FPP. A detailed life style questionnaire was administered to all subjects.
      Iron, ferritin, transferrin receptors (Tf R) and malondialdehyde (MDA) in plasma
      were measured. The RBCs lysate was used for the estimation of superoxide
      dismutase (SOD) and glutathione peroxidase (GPx). The total and free iron
      concentration as well as analysis of oxidative stress in the feces was measured.
      FPP-supplemented subjects showed a significantly lower degree of gastrointestinal
      discomfort (p less than 0.05) and abolished the iron supplementation-induced
      increase of MDA (p less than 0.001) and the depletion of SOD and GPx (p less than
      0.01). Moreover, the nutraceutical co-administration brought about a significant
      reduction of gut oxidative damage and lower fecal content of either total and
      free iron (p less than 0.05 vs group A). Overall, group B showed a better
      TfR/ferritin ratio response (p less than 0.05 vs group A). While iron
      supplementation maintains its clinical relevance considering the prevalence of
      iron deficiency among females, a careful clinical evaluation and a protective
      nutraceutical co-administration, as our data suggest with FPP, should be
      considered. 

PMID- 24750792
TI  - The use of engineered biomaterial Bone Plexur M(r) in benign epiphyseal tumors:
      our experience at 20 months of follow-up.
AB  - The objective is to reconstruct the subchondral bone after curettage of benign
      tumors located in the epiphysis, a relevant topic in oncological orthopedics.
      Several bones substituted are commercially available, yet none of these are
      suitably moldable to repair or be placed in the bone defect; although autologous
      bone for little defects and homologous for bigger defects are still considered
      the standard in reconstruction, we verify the ability to adapt and support
      articular cartilage through the application of Plexur M (Registered Trademark), a
      newly engineered biomaterial bone. In the present study, we enrolled the first
      ten consecutive cases referred to our department, where patients were affected by
      a benign epiphyseal tumor destroying the subchondral bone through to the
      articular cartilage. Every patient underwent curettage of the disease, apposition
      of a newly engineered biomaterial bone and filling with homologous morselized
      bone. The quality of reconstruction was evaluated by two surgeons and by a
      radiologist based on the achievement of surgical objectives and comparing pre and
      postoperative imaging. In seven out of eight cases of lesions located in the
      lower limbs the quality of reconstruction was considered good, restoring an
      adequate support to the articular cartilage. The quality of the remaining case
      was considered poor probably due to the extent of the spread of the disease,
      which destroyed the entire proximal tibial epiphysis. In the two cases where the
      disease was located in the upper limbs, the Plexur M application restored support
      to the articular cartilage sufficiently well. However, in the case of a giant
      cell tumor of the distal radial epiphysis there was a slight reabsorption of the
      morselized homologous bone. Our series suggest that Plexur M should be considered
      a valid option for orthopedic surgeons in restoring adequate mechanical support
      to the articular cartilage; nevertheless, considering its high cost, its use
      might be reserved to selected cases until further studies can verify the
      integration process, the effects on the survival of the articular cartilage and
      on the prevention of premature osteoarthritis. 

PMID- 24750793
TI  - Cathelicidin LL-37 in bronchoalveolar lavage and epithelial lining fluids from
      healthy individuals and sarcoidosis patients.
AB  - Sarcoidosis is a granulomatous disease of unknown etiology most often
      characterized by pulmonary manifestations. Changes in an innate immune system,
      involving antimicrobial peptides, have been noted during the course of pulmonary
      sarcoidosis. This study focuses on the level of LL-37 peptide, the only human
      cathelicidin, additionally characterized by a wide range of pleiotropic
      activities, in pulmonary sarcoidosis. A cross-sectional study was conducted in
      groups of 32 patients with sarcoidosis and 12 healthy individuals.
      Bronchoalveolar lavage fluid (BALF) sampling, followed by LL-37 measurements by
      mass spectrometry combined with previous immunoaffinity purification, was
      performed. Based on urea levels, concentrations of LL-37 in epithelial lining
      fluid (ELF) were calculated. The levels of LL-37 peptide in BALF samples derived
      from patients with pulmonary sarcoidosis (median: 17.45 pg/ml, 25th-75th
      percentile: 8.05-28.33 pg/ml) were significantly higher compared to the healthy
      group (median: 6.38 pg/ml, 25th-75th percentile: 4.90-11.55 pg/ml) (U Mann
      Whitney test, p=0.04). Assessment of LL-37 in ELF confirmed the differences
      across the groups that were observed in BALF. The level of LL-37 in patients with
      sarcoidosis (median: 2.25 ng/ml, 25th-75th percentile: 1.03-5.06 ng/ml) was again
      higher compared to healthy individuals (median: 0.62 ng/ml, 25th-75th percentile:
      0.43-2.17 ng/ml) (p=0.06, Mann-Whitney U test). The results of this study
      demonstrate that the level of LL-37 peptide is elevated in pulmonary compartment
      affected by sarcoidosis. This might have a meaning in the pathomechanism of the
      disease, especially taking into consideration versatile activity of human
      cathelicidin revealed in numerous experimental studies during the last years.

PMID- 24750794
TI  - Efficacy and safety of gammadeltaT cell-based tumor immunotherapy: a meta
      analysis.
AB  - Vgamma9Vdelta2 T cells are important effector cells that may play a role in the
      anti-tumor immune response. Their capability to exert MHC-nonrestricted lytic
      activity against different tumor cells in vitro and their detection among tumor
      infiltrating lymphocytes in a variety of human cancers have supported the
      development of Vgamma9Vdelta2 T cell-based immunotherapy in the context of novel
      treatment against cancer. Accordingly, promising reports from recent clinical
      trials support the use of V gamma9Vdelta2 T cells as immunotherapeutic agents,
      either via adoptive transfer of ex-vivo expanded V gamma9Vdelta2 T cells or in
      vivo activation of V gamma9Vdelta2 T cells with compounds such as phosphoantigens
      or aminobisphosphonates. In this study we have performed a meta-analysis to
      assess the objective efficacy and safety of V gamma9Vdelta2 T cell-based
      immunotherapy. Database including Pubmed, Web of Science and SCOPUS were
      investigated to identify relevant studies. Thirteen clinical trials involving
      patients with advanced or metastatic cancer were selected. In order to estimate
      the strength of association between V gamma9Vdelta2 T cell-based immunotherapy
      and favorable clinical effect or toxicity grade we used event rate (ER) with 95
      percent confidence interval (CI). The total effective rate provided significant
      results (ER = 0.407; P <0.014) while no correlation was found between serious
      adverse effects and Vgamma9Vdelta2 T cell-based therapy. This meta-analysis
      demonstrates that Vgamma9Vdelta2 T cell-based immunotherapy improves overall
      survival and, in view of its low toxicity grade, provides a proof of principle
      for its utilization as adjuvant to conventional therapies for
      resistant/refractory patients care.

PMID- 24750795
TI  - Basophils are rapidly mobilized following initial aeroallergen encounter in naive
      mice and provide a priming source of IL-4 in adaptive immune responses.
AB  - Chronic aeroallergen inhalation elicits the expansion of IL-4-producing Th2 cells
      and the production of IgE antibodies. In sensitized subjects, who have
      established IgE and Th2 responses, re-exposure to allergen leads to rapid
      recruitment of basophils, which are thought to be important effectors of late
      phase allergic reactions. Several investigations of responses to parasites and
      injected antigens have identified an additional role for basophils as innate
      immune effectors during initial antigen encounter in immunologically naive hosts.
      These cells constitutively express IL-4 and promote Th2 polarized adaptive
      responses to such antigens. Their early recruitment and modulation of cellular
      immune responses to natural inhaled allergens in the airways has been scarcely
      investigated. In this study, basophils were enumerated in lung tissue, blood and
      spleen from BALB/c mice in the first days after inhalation of an aqueous extract
      of the allergen, Aspergillus fumigatus (Af). Af inhalation induced rapid
      increases in basophil numbers in the lung, blood and spleen. This was Rag-1-,
      MyD88- and IL-3-independent. The basophils expressed abundant IL-4. Their
      depletion during Af sensitization resulted in an attenuated induction of both IL
      4 producing Th lymphocytes and specific IgE and IgG1 responses to an inhaled
      protein antigen, ovalbumin, which was co-administered. Our results suggest that
      basophils are rapidly recruited to the airways of naive mice following initial
      fungal allergen exposure, produce IL-4 and influence the development of the
      adaptive immune response. 

PMID- 24750796
TI  - Olea Europea-derived phenolic products attenuate antinociceptive morphine
      tolerance: an innovative strategic approach to treat cancer pain.
AB  - Morphine and related opioid drugs are currently the major drugs for severe pain.
      Their clinical utility is limited in the management of severe cancer pain due to
      the rapid development of tolerance. Restoring opioid efficacy is therefore of
      great clinical importance. A great body of evidence suggests the key role of free
      radicals and posttranslational modulation in the development of tolerance to the
      analgesic activity of morphine. Epidemiological studies have shown a relationship
      between the Mediterranean diet and a reduced incidence of pathologies such as
      coronary heart disease and cancer. A central hallmark of this diet is the high
      consumption of virgin olive oil as the main source of fat which contains
      antioxidant components in the non-saponifiable fraction, including phenolic
      compounds absent in seed oils. Here, we show that in a rodent model of opiate
      tolerance, removal of the free radicals with phenolic compounds of olive oil such
      as hydroxytyrosol and oleuropein reinstates the analgesic action of morphine.
      Chronic injection of morphine in mice led to the development of tolerance and
      this was associated with increased nitrotyrosin and malondialdehyde (MDA)
      formation together with nitration and deactivation of MnSOD in the spinal cord.
      Removal of free radicals by hydroxytyrosol and oleuropein blocked morphine
      tolerance by inhibiting nitration and MDA formation and replacing the MnSOD
      activity. The phenolic fraction of virgin olive oil exerts antioxidant activities
      in vivo and free radicals generation occurring during chronic morphine
      administration play a crucial role in the development of opioid tolerance. Our
      data suggest novel therapeutic approach in the management of chronic cancer pain,
      in particular for those patients who require long-term opioid treatment for pain
      relief without development of tolerance.

PMID- 24750797
TI  - Evaluation of the effects of a probiotic supplementation with respect to placebo
      on intestinal microflora and secretory IgA production, during antibiotic therapy,
      in children affected by recurrent airway infections and skin symptoms.
AB  - Antibiotic therapy, especially in pediatric patients, is often associated with
      significant modifications of the gut microflora, which can lead to intestinal
      dysbiosis and influence intestinal physiology and immune system functionality.
      Herein we report the results from a double blind controlled clinical trial in 77
      pediatric patients affected by recurrent airway infections, receiving antibiotic
      therapy with amoxicillin and clavulanic acid. A group was treated with an oral
      probiotic preparation composed of Lactobacillus paracasei ssp.paracasei CRL-431,
      Bifidobacterium BB-12, Streptococcus thermophilus TH-4 and a
      fructooligosaccharide (FOS) during and after antibiotic therapy for seven days,
      while the other group received placebo. The study revealed a reduction in the
      Clostridia population, with a contemporary increase in Bifidobacteria and
      Lactobacilli in fecal samples in the probiotic group and an increase in the
      Enterobacteria population in the placebo group. Moreover, there was a decreasing
      trend in secretory IgA production in the probiotic group. Some relevant, but not
      statistically significant probiotic supplementation effects were identified. 

PMID- 24750798
TI  - The effect of hydroxyapatite coated screw in the lateral fragility fractures of
      the femur. A prospective randomized clinical study.
AB  - Due to a growing numbers of lateral fragility fractures of the femur and their
      high social costs the need to work out an effective strategy in order to find a
      better solution for these patients is warranted. From January 2010 to July 2011,
      we carried out a prospective randomized clinical study comparing the results of
      patients with femoral lateral fractures treated by nail and cephalic
      hydroxyapatite coated screws (study group including 27 patients) compared to the
      patients with the same fractures treated with nail and head standard screws
      (control group including 27 patients). We defined the two parts of the femoral
      neck as ROI 1 (under the head screw) and ROI 2 (above the femoral screw) on the
      AP view. The bone density of the two areas was calculated using DEXA at T0 (1st
      day post-surgery), at T1 (40th day post-surgery), at T2 (3 months later), at T3
      (1 year later). The clinical-radiography evaluations were based on the Harris Hip
      Score (HHS), ADL test and x-ray views of the hip. As far as the bone mineral
      density average of ROI 1 and ROI 2 is concerned, we found a significant
      statistical increase at T1 and T3 in the study group, while it was not
      significant in the control group. We could account for this data through the
      higher mechanical stability of hydroxyapatite coated screws than standard screws.
      In fact, this material was responsible for improved implant osteointegration.
      Thanks to a 1 year follow-up we were able to demonstrate the implant utility
      associated with augmentation and the importance of densitometry exams such as
      easily repeatable and low cost diagnostics to prevent the onset of complications
      linked to screw loosening. 

PMID- 24750799
TI  - Immunomodulating treatment with low dose interleukin-4, interleukin-10 and
      interleukin-11 in psoriasis vulgaris.
AB  - Psoriasis is a chronic inflammatory skin disease affecting approximately 2-3
      percent of the world population; it is characterised by hyperproliferation and
      hyperplasia of the superficial layers of the epidermis. Inappropriate signals
      released by the immune system determine an altered keratinocyte differentiation,
      resulting in the formation of desquamating, thickened, inflamed and erythematous
      plaques. The aim of this investigation was to study the pharmacological activity
      and safety of three low dose cytokines, Guna-Interleukin 4, Guna-Interleukin 10
      and Guna-Interleukin 11 at the concentration of 10 fg/ml in patients affected by
      moderate to slight psoriasis vulgaris. The multicenter, double-blind, randomized,
      placebo-controlled clinical trial involved 48 patients who were enrolled and
      followed up according to a 8-month experimental project. All patients received,
      according to a cross-over model, either the experimental treatment or placebo,
      alternatively. Globally, in the 41 evaluated patients it was observed a PASI
      significant reduction (Friedman test: p=0.00960). The DLQI too decreased
      significantly in all subjects compared to baseline (Friedman test: p=0.00007).
      The safety of the treatment with three low dose cytokines administered
      simultaneously was proved; no adverse event was reported during the whole trial. 

PMID- 24750800
TI  - White mulberry supplementation as adjuvant treatment of obesity.
AB  - Body weight is controlled by our genes and managed by a neuro-hormonal system, in
      particular by insulin and glucagon. The meristematic extract of Japanese white
      mulberry blocks the alpha-glucosidase and then the intestinal hydrolysis of
      polysaccharides, thereby reducing the glycaemic index of carbohydrates. The
      target of our research was to evaluate the adjuvant slimming effect of the
      extract of white Japanese mulberry in the dietetic treatment of some patients who
      are obese or overweight. 46 overweight people were enrolled and divided into two
      subgroups: the subjects of both subgroups were given an identical balanced diet
      of 1300 kcal: subjects of the subgroup alpha received 2400 mg of white Japanese
      mulberry extract, the subgroup b subjects receive placebo. Each subgroup was
      followed-up every 30 days at 30, 60 and 90 days of treatment. Both in the
      periodic inspections and in the final inspection measurements of body weight and
      waist circumference in all the subjects and thigh circumference in women only
      were repeated. All subjects repeated blood tests. In the subgroup alpha, weight
      loss was about 9 kg in 3 months, equal to approximately 10 percent of the initial
      weight, significantly higher than subgroup beta (P<0.0001); moreover, the plasma
      insulin and glucose curves of the volunteers in this subgroup at the end of the
      trial were lower than those performed at the time of enrolment. In the 20 women
      of the beta subgroup treated with only low-calorie diet and with placebo, weight
      reduction was globally of 3.2 kg, approximately equal to 3 percent of the initial
      weight; moreover, the blood glucose curves and the insulin curves showed a slight
      decline compared to baseline, but not so significantly as was the case for group
      alpha. Waist circumference and thigh circumference (in women) decreased in all
      participants, obviously more evidently in subjects who lost more kg. The extract
      of white Japanese mulberry may represent a reliable adjuvant therapy in the
      dietetic treatment of some patients who are obese or overweight. 

PMID- 24750801
TI  - Diurnal trajectories of salivary cortisol, salivary alpha-amylase and
      psychological profiles in oral lichen planus patients.
AB  - Although many reports have been published on the link between oral lichen planus
      (OLP) and the stress-related neuro-psycho-endocrine clinical features of the
      disease over the last 20 years, the data still remain controversial. Therefore,
      the aim of this study was to explore the personality traits of OLP subjects and
      assess the subjects' capability of coping with stress challenges. Cortisol and
      alpha-amylase were measured as reliable markers of the hypothalamic-pituitary
      adrenal (HPA) axis and autonomic nervous system (ANS) activities in salivary
      samples collected by the participants at their home during the sampling day
      (07:30, 12:00, and 19:30). Compared with the healthy controls, the OLP patients
      demonstrated a less effective coping ability, had higher scores in stress
      perception and loneliness, and had no significant variation in their anxiety and
      depressive symptoms. The OLP patients also showed dysregulation of the HPA axis
      activity with a significant reduction of diurnal salivary cortisol production,
      which was particularly significant in the morning hours. No significant variation
      was found in the OLP salivary alpha-amylase diurnal fluctuation and production,
      which was measured at the same time point as that for cortisol. In conclusion, we
      report that OLP subjects had a reduced capability of coping with stress events
      and presented a dysregulation of HPA axis activity with hypocortisolism detected
      in the morning hours.

PMID- 24750802
TI  - Safety profile and protocol prevention of adverse reactions to uroangiographic
      contrast media in diagnostic imaging.
AB  - The purpose of the study is to examine the incidence of adverse reactions caused
      by non-ionic contrast media in selected patients after desensitization treatment
      and to evaluate the safety profile of organ iodine contrast media (i.c.m.) in a
      multistep prevention protocol. In a population of 2000 patients that had received
      a CT scan, 100 patients with moderate/high risk for adverse reactions against
      iodinated contrast agents followed a premedication protocol and all adverse
      reactions are reported and classified as mild, moderate or severe. 1.7 percent of
      the pre-treated patients reported a mild, immediate type reaction to iodine
      contrast; of these five patients with allergy 0.71 percent had received iomeprol,
      0.35 percent received ioversol and 0.71 percent received iopromide. The incidence
      of adverse reactions was reported to be higher (4 out of 5 patients) among those
      that referred a history of hypersensitivity against iodinated i.c.m. Although
      intravenous contrast materials have greatly improved, especially in terms of
      their safety profile, they should not be administered if there isn't a clear or
      justified indication. In conclusion, even if we know that the majority of these
      reactions are idiosyncratic and unpredictable we propose, with the aim of
      improving our knowledge on this subject, a multicenter study, based on skin
      allergy tests (prick test, patch test, intradermal reaction) in selected patients
      that have had previous experiences of hypersensitivity against parenteral organ
      iodine contrast media.

PMID- 24750803
TI  - Challenges in the sequencing of therapies for the management of metastatic
      castration-resistant prostate cancer.
AB  - Prior to 2010, docetaxel was the standard option for chemotherapy in men with
      metastatic castration-resistant prostate cancer (mCRPC). Today, the picture is
      vastly different: several additional therapies have each demonstrated a survival
      benefit such that we now have chemotherapy (cabazitaxel), androgen suppressive
      agents (abiraterone acetate and enzalutamide), a cellular vaccine (sipuleucel-T)
      and radium-233 (for symptomatic bone metastases). With several other agents in
      the pipeline for late-stage disease, the future looks promising for mCRPC. As the
      available data are not able to inform as to the optimum sequencing of therapy,
      this remains a challenge. This paper draws on insights from published and ongoing
      clinical studies to provide a practical patient-focused approach to maximize the
      benefits of the current therapeutic armamentarium. Preliminary sequencing
      suggestions are made based on clinical trial criteria. But until more data become
      available, clinical gestalt, experience, cost and individual patient preferences
      will continue to drive choices. 

PMID- 24750805
TI  - The more the merrier? Reduced fecal microbiota diversity in preterm infants
      treated with antibiotics.

PMID- 24750804
TI  - Another explanation for breast milk jaundice.

PMID- 24750806
TI  - The natural history of HIV-associated lipodystrophy in the changing scenario of
      HIV infection.
AB  - OBJECTIVES: In long-term HIV-infected patients, peripheral lipoatrophy (LA) and
      central lipohypertrophy (LH) appear to be related to the same insults (virus and
      antiretroviral drugs), but are likely to be associated with different fat depot
      physiologies. The objective of this study was to describe the natural history of
      lipodystrophy assessed using dual energy X-ray absorptiometry (DEXA) and computed
      tomography (CT) in a large HIV out-patients metabolic clinic. METHODS: An
      observational retrospective study was carried out including HIV-infected patients
      recruited at the Metabolic Clinic of Modena, Modena, Italy, who were assessed for
      lipodystrophy and had at least two anthropometric evaluations using DEXA for leg
      fat per cent mass and abdominal CT for visceral adipose tissue (VAT). Factors
      associated with leg fat per cent and VAT changes were analysed using
      multivariable generalized estimating equation (GEE) regression models. RESULTS: A
      total of 6789 DEXAs and 7566 CT scans were evaluated in the observation period. A
      total of 1840 patients were included; the mean age was 45.2 +/- 7.2 (standard
      deviation) years, 621 (34%) were women, and the median HIV infection duration was
      176 (interquartile range 121-232) years. According to the GEE multivariable
      regression analysis, leg fat per cent evaluated with DEXA appeared to increase
      over calendar years (beta = 0.92; P < 0.001); moreover, a progressive increase in
      VAT was observed in the cohort (beta = 5.69; P < 0.001). No association with
      antiretroviral drugs was found. CONCLUSIONS: In our study, neither LA nor LH
      appeared to be associated with antiretroviral drug exposure. We observed a
      progressive increase in LH in HIV-infected patients over calendar years. This
      anthropometric change, together with loss of appendicular lean mass, could
      describe a physiological aging process in HIV-infected patients.

PMID- 24750807
TI  - Prevalence and antibiotic resistance of Enterococcus spp. isolated from retail
      cheese, ready-to-eat salads, ham, and raw meat.
AB  - Food specimens were analyzed in order to research Enterococcus spp.: 636 samples
      of raw meat (227 beef, 238 poultry, and 171 pork), 278 samples of cheese (110
      fresh soft cheese and 168 mozzarella cheese), 214 samples of ready-to-eat salads,
      and 187 samples of ham. 312 strains of Enterococcus spp samples were isolated,
      then identified and submitted to susceptibility tests against 11 antimicrobial
      agents. The predominant species were Enterococcus faecalis in raw meat and
      Enterococcus faecium in retail products. Low percentages of microorganisms were
      resistant to vancomycin (3.53%), teicoplanin (2.24%), linezolid (0.32%), and
      amoxicillin in combination with clavulanic acid (0.32%). A high percentage of
      resistance was noted in E. faecalis at high level gentamicin (21.9%) and
      tetracycline (60.6%). In general, strains of E. faecalis were more resistant than
      E. faecium. Enterococci should be considered not only potential pathogens, but
      also a reservoir of genes encoding antibiotic resistance which can be transferred
      to other microorganisms. Continuous monitoring of their incidence and emerging
      resistance is important in order to identify foods which potentially represent a
      real risk to the population, and to ensure effective treatment of human
      enterococcal infections. 

PMID- 24750808
TI  - In situ investigation of Geobacillus stearothermophilus spore germination and
      inactivation mechanisms under moderate high pressure.
AB  - Bacterial spores are a major concern for food safety due to their high resistance
      to conventional preservation hurdles. Innovative hurdles can trigger bacterial
      spore germination or inactivate them. In this work, Geobacillus
      stearothermophilus spore high pressure (HP) germination and inactivation
      mechanisms were investigated by in situ infrared spectroscopy (FT-IR) and
      fluorometry. G. stearothermophilus spores' inner membrane (IM) was stained with
      Laurdan fluorescent dye. Time-dependent FT-IR and fluorescence spectra were
      recorded in situ under pressure at different temperatures. The Laurdan spectrum
      is affected by the lipid packing and level of hydration, and provided information
      on the IM state through the Laurdan generalized polarization. Changes in the -CH2
      and -CH3 asymmetric stretching bands, characteristic of lipids, and in the amide
      I' band region, characteristic of proteins' secondary structure elements, enabled
      evaluation of the impact of HP on endospores lipid and protein structures. These
      studies were complemented by ex situ analyses (plate counts and microscopy). The
      methods applied showed high potential to identify germination mechanisms,
      particularly associated to the IM. Germination up to 3 log10 was achieved at 200
      MPa and 55  degrees C. A molecular-level understanding of these mechanisms is
      important for the development and validation of multi-hurdle approaches to
      achieve commercial sterility. 

PMID- 24750809
TI  - Purification and characterization of antifungal compounds from Lactobacillus
      plantarum HD1 isolated from kimchi.
AB  - Strain HD1 with antifungal activity was isolated from kimchi and identified as
      Lactobacillus plantarum. Antifungal compounds from Lb. plantarum HD1 were active
      against food- and feed-borne filamentous fungi and yeasts in a spot-on-the-lawn
      assay. Antifungal activity of Lb. plantarum HD1 was stronger against filamentous
      fungi than yeast. Antifungal compounds were purified using solid phase extraction
      (SPE) and recycling preparative-HPLC. Structures of the antifungal compounds were
      elucidated by electrospray ionization-mass spectrometry and nuclear magnetic
      resonance. Active compounds from Lb. plantarum HD1 were identified as 5
      oxododecanoic acid (MW 214), 3-hydroxy decanoic acid (MW 188), and 3-hydroxy-5
      dodecenoic acid (MW 214). To investigate the potential application of these
      antifungal compounds for reduction of fungal spoilage in foods, Korean draft rice
      wine was used as a food model. White film-forming yeasts were observed in control
      draft rice wine after 11 days of incubation. However, film-forming yeasts were
      not observed in draft rice wine treated with SPE-prepared culture supernatant of
      Lb. plantarum HD1 (equivalent to 2.5% addition of culture supernatant) until 27
      days of incubation. The addition of antifungal compounds to Korean draft rice
      wine extended shelf-life up to 27 days at 10  degrees C without any sterilization
      process. Therefore, the antifungal activity of Lb. plantarum HD1 may lead to the
      development of powerful biopreservative systems capable of preventing food- and
      feed-borne fungal spoilage. 

PMID- 24750810
TI  - Combined treatments of high-pressure with the lactoperoxidase system or
      lactoferrin on the inactivation of Listeria monocytogenes, Salmonella Enteritidis
      and Escherichia coli O157:H7 in beef carpaccio.
AB  - The effect of high hydrostatic pressure (HHP) treatments in combination with the
      lactoperoxidase system (LPOS) or activated lactoferrin (ALF) on Listeria
      monocytogenes, Salmonella enterica subsp. enterica serovar Enteritidis and
      Escherichia coli O157:H7 was investigated in cured beef carpaccio stored at 8 
      degrees C or 22  degrees C during 7 d. HHP (450 MPa for 5 min) reduced pathogen
      levels by 1-3 log units and the antimicrobial effect remained during 7 d of
      storage under temperature abuse conditions at 8  degrees C and at 22  degrees C.
      The individual application of LPOS and ALF did not affect the survival of the
      three pathogens studied during storage. However, a synergistic bactericidal
      interaction between LPOS and HHP was observed against S. Enteritidis and E. coli
      O157:H7. Combined treatments of HHP with LPOS would be useful to reduce the
      intensity of pressurization treatments diminishing changes in the quality of meat
      products. 

PMID- 24750811
TI  - Exploring the use of Saccharomyces cerevisiae commercial strain and
      Saccharomycodes ludwigii natural isolate for grape marc fermentation to improve
      sensory properties of spirits.
AB  - In Mediterranean countries the most diffuse practice to obtain the valorization
      of grape marc, the main by-product from winemaking, is the production of spirits.
      During this process, marc storage for sugar fermentation represents a crucial
      step, since side-fermentations leading to off-flavours production can very easily
      occur. In this study we evaluated the effect of the addition of two yeast
      strains, inoculated separately at the beginning of the storage period, into marcs
      from two Italian grape varieties with the aim to control the development of
      autochthonous microbiota and to improve spirit quality. The presence of the
      inoculated strains was monitored by means of PCR-based approaches. A commercial
      Saccharomyces cerevisiae strain, chosen as this species is notably the best
      ethanol producer, showed excellent ability to dominate the autochthonous
      microflora and to reduce off-flavours as demonstrated by chemical analysis and
      sensory evaluation. A Saccharomycodes ludwigii strain, chosen for increasing
      varietal compounds thus enhancing spirit aroma, showed a level of implantation
      not sufficient to assure a clear beneficial effect on quality. The implantation
      level of this strain was affected by S. cerevisiae competition since the highest
      level was found in grape marc with lower sugar content, where indigenous S.
      cerevisiae were less persistent. 

PMID- 24750812
TI  - Metagenomic analysis of the microbial community in kefir grains.
AB  - Kefir grains as a probiotic have been subject to microbial community
      identification using culture-dependent and independent methods that target
      specific strains in the community, or that are based on limited 16S rRNA
      analysis. We performed whole genome shotgun pyrosequencing using two Turkish
      Kefir grains. Sequencing generated 3,682,455 high quality reads for a total of
      ~1.6 Gbp of data assembled into 6151 contigs with a total length of ~24 Mbp.
      Species identification mapped 88.16% and 93.81% of the reads rendering 4 Mpb of
      assembly that did not show any homology to known bacterial sequences. Identified
      communities in the two grains showed high concordance where Lactobacillus was the
      most abundant genus with a mapped abundance of 99.42% and 99.79%. This genus was
      dominantly represented by three species Lactobacillus kefiranofaciens,
      Lactobacillus buchneri and Lactobacillus helveticus with a total mapped abundance
      of 97.63% and 98.74%. We compared and verified our findings with 16S
      pyrosequencing and model based 16S data analysis. Our results suggest that
      microbial community profiling using whole genome shotgun data is feasible, can
      identify novel species data, and has the potential to generate a more accurate
      and detailed assessment of the underlying bacterial community, especially for low
      abundance species. 

PMID- 24750813
TI  - Population structure and aflatoxin production by Aspergillus Sect. Flavi from
      maize in Nigeria and Ghana.
AB  - Aflatoxins are highly toxic carcinogens that contaminate crops worldwide.
      Previous studies conducted in Nigeria and Ghana found high concentrations of
      aflatoxins in pre- and post-harvest maize. However, little information is
      available on the population structure of Aspergillus Sect. Flavi in West Africa.
      We determined the incidence of Aspergillus Sect. Flavi and the level of aflatoxin
      contamination in 91 maize samples from farms and markets in Nigeria and Ghana.
      Aspergillus spp. were recovered from 61/91 maize samples and aflatoxins B1 and/or
      B2 occurred in 36/91 samples. Three samples from the farms also contained
      aflatoxin G1 and/or G2. Farm samples were more highly contaminated than were
      samples from the market, in terms of both the percentage of the samples
      contaminated and the level of mycotoxin contamination. One-hundred-and-thirty
      five strains representative of the 1163 strains collected were identified by
      using a multilocus sequence analysis of portions of the genes encoding
      calmodulin, beta-tubulin and actin, and evaluated for aflatoxin production. Of
      the 135 strains, there were 110 - Aspergillus flavus, 20 - Aspergillus tamarii, 2
      - Aspergillus wentii, 2 - Aspergillus flavofurcatus, and 1 - Aspergillus
      parvisclerotigenus. Twenty-five of the A. flavus strains and the A.
      parvisclerotigenus strain were the only strains that produced aflatoxins. The
      higher contamination of the farm than the market samples suggests that the
      aflatoxin exposure of rural farmers is even higher than previously estimated
      based on reported contamination of market samples. The relative infrequency of
      the A. flavus SBG strains, producing small sclerotia and high levels of both
      aflatoxins (B and G), suggests that long-term chronic exposure to this mycotoxin
      are a much higher health risk in West Africa than is the acute toxicity due to
      very highly contaminated maize in east Africa. 

PMID- 24750814
TI  - Microbiological sampling plan based on risk classification to verify supplier
      selection and production of served meals in food service operation.
AB  - Food service operations are confronted with a diverse range of raw materials and
      served meals. The implementation of a microbial sampling plan in the framework of
      verification of suppliers and their own production process (functionality of
      their prerequisite and HACCP program), demands selection of food products and
      sampling frequencies. However, these are often selected without a well described
      scientifically underpinned sampling plan. Therefore, an approach on how to set-up
      a focused sampling plan, enabled by a microbial risk categorization of food
      products, for both incoming raw materials and meals served to the consumers is
      presented. The sampling plan was implemented as a case study during a one-year
      period in an institutional food service operation to test the feasibility of the
      chosen approach. This resulted in 123 samples of raw materials and 87 samples of
      meal servings (focused on high risk categorized food products) which were
      analyzed for spoilage bacteria, hygiene indicators and food borne pathogens.
      Although sampling plans are intrinsically limited in assessing the quality and
      safety of sampled foods, it was shown to be useful to reveal major non
      compliances and opportunities to improve the food safety management system in
      place. Points of attention deduced in the case study were control of Listeria
      monocytogenes in raw meat spread and raw fish as well as overall microbial
      quality of served sandwiches and salads. 

PMID- 24750815
TI  - Survival and growth of Listeria innocua treated by pulsed light technology:
      impact of post-treatment temperature and illumination conditions.
AB  - Inactivation of Listeria innocua by pulsed light (PL) was evaluated at different
      post-treatment temperature and illumination conditions. The impact of post-PL
      treatment temperature on L. innocua culturability was evaluated for cells
      cultured at 37  degrees C (optimal growth temperature) and 4  degrees C
      (classical refrigerated food temperature). For both culture conditions,
      significant higher reductions (up to 3 log) were observed after post-PL-treatment
      temperature of 4  degrees C than of 37  degrees C. Contrarily, L. innocua
      culturability after PL treatment increased up to 2.2 log in presence of daylight
      illumination in comparison to dark storage. This photorepair mechanism was
      quickly activated reaching the maximum photoreactivation level after only 30 min
      of illumination. Moreover, photorepair capacity was rapidly reduced by increasing
      the time in darkness from PL treatment to samples illumination, being completely
      lost after time in darkness equal or greater than 5 h. According to these
      findings, the combination of PL with post-treatment temperature of 4  degrees C
      has a synergistic effect on the inactivation of L. innocua, whereas post
      treatment daylight illumination has an antagonic effect on PL antimicrobial
      efficacy. Post-PL-treatment temperature and illumination conditions could be
      thereby considered important environmental factors to activate, inhibit or
      control the repair and/or growth of L. innocua survivors after PL treatment. 

PMID- 24750816
TI  - Application of capillary electrophoresis single-stranded conformation
      polymorphism (CE-SSCP) analysis for identification of fungal communities in
      cheese.
AB  - As major contributors of the ripening process, yeasts and filamentous fungi play
      a fundamental role in cheese-making. Still, there is no rapid and affordable
      identification method available for both yeasts and filamentous fungi encountered
      in cheeses. In the present study, we developed a method based on CE-SSCP analysis
      of nuclear ribosomal DNA ITS amplicons, along with a species pattern database
      comprising 37 fungal species. By combining analyses of the ITS1 and ITS2
      conformers, 25 out of 37 species were discriminated using CE-SSCP analysis. This
      reproducible and sensitive method was applied to determine the fungal community
      composition of 36 cheeses including blue-veined, pressed-cooked, pressed
      uncooked, red-smear and surface-mould ripened cheeses. Overall, each cheese
      contained between 1 and 6 fungal species and 23 different species of fungi were
      detected including 8 yeast species, 9 filamentous species and 6 unidentified
      species. Comparison of the fungal diversity obtained after cloning and sequencing
      (rDNA ITS) versus CE-SSCP for 8 cheeses showed that CE-SSCP was at least as
      exhaustive as cloning and sequencing of thirty clones per cheese. In conclusion,
      this CE-SSCP method was an effective tool to identify the fungi present in
      various cheese varieties and may be of interest for the cheese industry to
      rapidly describe the composition of cheese fungal communities. 

PMID- 24750817
TI  - Molecular methods used to estimate thermal inactivation of a prototype human
      norovirus: more heat resistant than previously believed?
AB  - Two molecular-based methods for estimating capsid integrity as a proxy for virus
      infectivity were used to produce thermal inactivation profiles of Snow Mountain
      virus (SMV), a prototype human norovirus (HuNoV). Monodispersed virus suspensions
      were exposed to 77, 80, 82 and 85  degrees C for various times, pre-treated with
      either propidium monoazide (PMA) or RNase, and subjected to RNA isolation
      followed by RT-qPCR amplification. D-values were 25.6 +/- 2.8, 3.1 +/- 0.1, 0.7
      +/- 0.04 and 0.2 +/- 0.07 min at 77, 80, 82 and 85  degrees C, respectively for
      PMA-treated SMV; and 16.4 +/- 0.4, 3.9 +/- 0.2 0.9 +/- 0.3 and 0.12 +/- 0.00 min
      at 77, 80, 82 and 85  degrees C, respectively for RNase-treated SMV.
      Corresponding zD values were 3.80  degrees C and 3.71  degrees C for PMA and
      RNase-treated virus, respectively. Electron microscopy data applied to heat
      treated virus-like particles supported this relatively high degree of thermal
      resistance. The data suggest that SMV is more heat resistant than common
      cultivable HuNoV surrogates. Standardized thermal inactivation methods (such as
      milk pasteurization) may not be stringent enough to eliminate this virus and
      perhaps other HuNoV. 

PMID- 24750818
TI  - Identification of airborne microbiota in selected areas in a health-care setting
      in South Africa.
AB  - BACKGROUND: The role of bio-aerosols in the spread of disease and spoilage of
      food has been described in numerous studies; nevertheless this information at
      South African hospitals is limited. Attributable to their size, bio-aerosols may
      be suspended in the air for long periods placing patients at risk of infection
      and possibly settling on surfaces resulting in food contamination. The aim of the
      study is to assess the microbial composition of the air in the kitchen and
      selected wards at a typical district hospital in South Africa. Air samples were
      collected using the settle plates and an SAS Super 90 air sampler by impaction on
      agar. These microbial samples were quantified and identified using Matrix
      Assisted Laser Desorption/Ionization Time of Flight Mass Spectrometry (MALDI-TOF
      MS) and Analytic Profile Index (API). RESULTS: Microbial counts were found to be
      higher in the fourth (<=6.0 * 101 cfu/m(-3)) sampling rounds when compared to the
      first (>=2 cfu/m(-3)), second (<=3.0 * 101 cfu/m(-3)) and third (<=1.5 * 101
      cfu/m(-3)) sampling rounds. Genera identified included Bacillus, Kocuria,
      Staphylococcus, Arthrobacter, Candida, Aureobasidium, Penicillium and Phoma
      amongst others. The presence of these pathogens is of concern, attributable to
      their ability to cause diseases in humans especially in those with suppressed
      host immunity defenses. Furthermore, fungal genera identified (e.g. Candida) in
      this study are also known to cause food spoilage and fungal infections in
      patients. CONCLUSION: Results from this study indicate the importance of air
      quality monitoring in health-care settings to prevent possible hospital-acquired
      infections and contamination of hospital surfaces including food contact surfaces
      by airborne contaminants.

PMID- 24750820
TI  - Acute lower respiratory tract infections in soldiers, South Korea, April 2011
      March 2012.
AB  - During April 2011-March 2012, we retrospectively reviewed medical records for
      South Korea soldiers to assess the etiology and epidemiology of acute viral lower
      respiratory tract infections. Adenovirus was the most commonly identified virus
      (63.2%) and the most common cause of pneumonia (79.3%) and hospitalization
      (76.6%); 3 soldiers died of adenovirus-related illness. 

PMID- 24750821
TI  - [Environmental pollution and childhood renal injury].

PMID- 24750819
TI  - Reduced immune cell infiltration and increased pro-inflammatory mediators in the
      brain of Type 2 diabetic mouse model infected with West Nile virus.
AB  - BACKGROUND: Diabetes is a significant risk factor for developing West Nile virus
      (WNV)-associated encephalitis (WNVE) in humans, the leading cause of arboviral
      encephalitis in the United States. Using a diabetic mouse model (db/db), we
      recently demonstrated that diabetes enhanced WNV replication and the
      susceptibility of mice to WNVE. Herein, we have examined immunological events in
      the brain of wild type (WT) and db/db mice after WNV infection. We hypothesized
      that WNV-induced migration of protective leukocytes into the brain is attenuated
      in the presence of diabetes, leading to a high viral load in the brain and severe
      disease in diabetic mice. METHODS: Nine-week old C57BL/6 WT and db/db mice were
      infected with WNV. Leukocyte infiltration, expression of cell adhesion molecules
      (CAM), neuroinflammatory responses, activation of astrocytes, and neuronal death
      were analyzed using immunohistochemistry, qRT-PCR, flow cytometry, and western
      blot. RESULTS: We demonstrate that infiltration of CD45+ leukocytes and CD8+T
      cells was significantly reduced in the brains of db/db mice, which was correlated
      with attenuated expression of CAM such as E-selectin and ICAM-1. WNV infection in
      db/db mice was associated with an enhanced inflammatory response in the brain.
      mRNA and protein levels of key chemokines such as CXCL10, CXCL1, CCL2, CCL5,
      CCL3, and G-CSF, and cytokines such as IL-1beta, TNF, IL-6, IFNgamma, and IL
      1alpha were significantly elevated in the brains of db/db mice compared to WT
      mice. Elevated levels of cytokines also correlated with increased astrocytes
      activation and neuronal damage in the brains of db/db mice. CONCLUSION: These
      data suggest that reduced leukocytes recruitment, in part, due to lower levels of
      CAM results in failure to clear WNV infection from the brain leading to increased
      production of inflammatory molecules, which mediates increased neuronal death and
      mortality in db/db mice. This is the first study to elucidate the expression of
      CAM and their correlation with the migration of leukocytes, specifically
      cytotoxic CD8+ T cells, in increasing disease severity in the diabetic mouse
      model.

PMID- 24750822
TI  - [Hazardous environmental factors causing renal damage in children].
AB  - Hazardous environmental factors invade the body through multiple routes,
      including ingestion, inhalation and absorption by contact with the skin and
      mucous membrane. They are from various sources and soil, water, air, building and
      decorative materials, foods and daily necessities are the main carriers.
      According to their physical and chemical properties and morphological
      characteristics, these hazardous factors are classified as metals, inorganic
      matter, organic matter, radioactive substances, biological toxins, viruses,
      bacteria, mycoplasmas, chlamydiae and parasites. They cause diseases through
      blood and urine and also have kidney susceptibility. This article suggests that
      pediatricians should fully understand the characteristics and seriousness of
      hazardous environmental factors that cause renal damage, and pay attention to the
      prevention and control of these factors so as to minimize renal damage in
      children. 

PMID- 24750823
TI  - [Heavy metal poisoning and renal injury in children].
AB  - Along with global environmental pollution resulting from economic development,
      heavy metal poisoning in children has become an increasingly serious health
      problem in the world. It can lead to renal injury, which tends to be misdiagnosed
      due to the lack of obvious or specific early clinical manifestations in children.
      Early prevention, diagnosis and intervention are valuable for the recovery of
      renal function and children's good health and growth. This paper reviews the
      mechanism of renal injury caused by heavy metal poisoning in children, as well as
      the clinical manifestations, diagnosis, and prevention and treatment of renal
      injury caused by lead, mercury, cadmium, and chromium. 

PMID- 24750824
TI  - [Research progress in mechanisms of drug-induced nephrotoxicity].
AB  - Drug-induced nephrotoxicity in children is dependent upon the histological,
      anatomical and physiological features of their kidneys and the structural and
      functional characteristics of drugs. The kidney is mainly composed of
      microvascular network and tubulointerstitial tissue, so drug-induced
      nephrotoxicity is usually manifested by interstitial nephropathy. The mechanisms
      of drug-induced nephrotoxicity include cytotoxicity (necrosis or apoptosis),
      ischemic injury, and immunological injury. Individual drugs cause renal damage by
      various mechanisms due to differences in chemical structure and pharmacology.
      This article reviews the main features of nephrotoxicity induced by common
      antibiotics (cephalosporins, aminoglycosides, vancomycin, carbapenems and
      amphotericin B), non-steroidal anti-inflammatory drugs, and cyclosporine A. 

PMID- 24750825
TI  - [Children's renal injury caused by food].
AB  - Mushroom and fish bile toxins are the most representative toxins of food origin.
      According to the clinical manifestations, renal injury caused by mushroom toxins
      can be divided into early-, late-, and delayed-onset. Fish bile toxins mainly
      cause acute renal tubular necrosis and food contamination related to renal injury
      includes chemical and biological contamination. Urinary calculus and renal
      failure caused by "poisonous milk powder" is a typical, food-related chemical
      contamination event. E.coli contaminated cucumber caused hemolytic uremic
      syndrome in 3 493 people. Contamination of the food chain is spreading from land
      to sea and to sky. It requires the efforts of the whole society to prevent human
      food chain contamination.

PMID- 24750826
TI  - [Environment and congenital urinary malformations].
AB  - The development of the kidneys and other organs of the urinary tract follows the
      natural rule of gene-environment-lifestyle interaction. Both intrinsic and
      extrinsic factors may be associated with the etiology of various kinds of urinary
      malformations, but the environmental factor is an extrinsic factor. Related
      literatures were reviewed in this paper, which focuses on the association of
      congenital urinary malformations with possible environmental factors. It is
      concluded that urinary malformation is associated with low birth weight, maternal
      disease, placental insufficiency, maternal drug exposure, and maternal exposure
      to environmental pesticides. Living environment and socioeconomic factors may
      also influence the incidence of urinary malformation. 

PMID- 24750827
TI  - [Recognizing pediatric acute kidney injury].
AB  - Acute kidney injury (AKI) is characterized by a reversible increase in blood
      concentration of creatinine and nitrogenous waste products and by the inability
      of the kidney to regulate fluid and electrolyte homeostasis appropriately. AKI in
      hospitalized patients is independently associated with increased morbidity and
      mortality in pediatric and adult populations. Continued reliance on serum
      creatinine and urine output for the diagnosis of AKI has resulted in an inability
      to provide successful therapeutic and supportive interventions to prevent and
      mitigate AKI. Research efforts over the last decade have foused on the discovery
      and validation of novel biomarkers to detect AKI prior to a change in kidney
      function and to make a differential diagnosis of AKI. 

PMID- 24750828
TI  - [Mutational analysis of MYO1E in Chinese children with familial steroid-resistant
      nephrotic syndrome].
AB  - OBJECTIVE: Steroid-resistant nephrotic syndrome (SRNS) with MYO1E mutations has
      been identified as autosomal recessive focal segmental glomerulosclerosis (FSGS).
      To date, only two homozygous mutations in the MYO1E gene were reported in three
      families with FSGS. This study aimed to examine mutations in the MYO1E gene in
      children with familial SRNS in the Han Chinese ethnic group. METHODS: Between
      2005 and 2010, peripheral blood samples were collected from the probands, their
      siblings and parents of four families with autosomal recessive SRNS in the Han
      Chinese ethnic group. Four probands were studied from nine patients. The
      mutational analysis of MYO1E was performed by polymerase chain reaction and
      direct DNA sequencing. Fifty-nine healthy volunteers with normal urine analysis
      were included as controls. RESULTS: Twenty-five MYO1E variants in the prohands
      from 4 families with SRNS were identified in this study. Among them, 24 variants
      were found in NCBI dbSNP. One heterozygous mutation IVS21-85G>A was found in the
      prohand from Family D, whereas it was absent in 59 normal Chinese controls. No
      splice site change caused by IVS21-85G>A was reported by analysis with NetGene2.
      CONCLUSIONS: MYO1E mutations are not a major cause of Chinese familial SRNS in
      this study.

PMID- 24750829
TI  - [Significance of serum cholesterol and fibrinogen in evaluating the risk of
      glomerulosclerosis in children with nephrotic syndrome].
AB  - OBJECTIVE: To investigate the significance of serum cholesterol and fibrinogen
      (Fib) in evaluating the risk of glomerulosclerosis in children with nephrotic
      syndrome. METHODS: Sixty-three children with primary nephrotic syndrome were
      divided into two groups according to their pathological types: minimal change
      glomerulopathy (MCG) (n=39) and focal segmental glomerulosclerosis (FSGS) groups
      (n=24). Serum levels of total cholesterol (TC), low-density lipoprotein
      cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), non-HDL-C and
      Fib and 24-hour urinary protein excretion were retrospectively analyzed. RESULTS:
      Serum levels of TC, non-HDL-C, and LDL-C were significantly higher in the FSGS
      group than in the MCG group (P<0.05), but there were no significant differences
      in HDL-C, Fib and 24-hour urinary protein excretion between the two groups
      (P>0.05). According to the results of logistic regression analysis, high levels
      of LDL-C, non-HDL-C and TC were risk factors for FSGS (P<0.05). In patients whose
      proteinuria did not disappear after taking enough glucocorticoid for 4 weeks, the
      level of non-HDL-C was significantly higher in the FSGS group than in the MCG
      group (P<0.05); there were no significant differences in TC, LDL-C, HDL-C, and
      Fib between the MCG and FSGS groups (P>0.05). CONCLUSIONS: Serum cholesterol,
      especially non-LDL-C, is of great significance in evaluating the risk of
      glomerulosclerosis in children with nephrotic syndrome. There is no sufficient
      evidence to support serum Fib as a marker for predicting glomerulosclerosis in
      these children.

PMID- 24750830
TI  - [Expression of tight junction protein claudin-2 in renal tissues and its
      significance in children with acute kidney injury].
AB  - OBJECTIVE: To examine changes in expression of tight junction protein claudin-2
      in the renal tissues of children with acute kidney injury (AKI), and to
      investigate the relationship of claudin-2 expression with renal pathological
      lesion and renal functional lesion. METHODS: Twenty-four children who were
      diagnosed with AKI and had renal biopsies between December 2009 and December 2011
      were included in the study. These patients were divided into mild AKI (n=7) and
      severe AKI groups (n=17). Children with isolated hematuria whose renal biopsy
      showed minor glomerular lesion were selected as the control group. Serum
      creatinine levels were measured by automatic biochemical analyzer.
      Tubulointerstitial damage was evaluated by renal pathological scores and
      expression of claudin-2 was examined by immunohistochemistry. The correlations of
      claudin-2 expression with renal pathological score and serum creatinine level
      were assessed by Pearson correlation analysis. RESULTS: The mild and severe AKI
      groups had significantly higher serum creatinine levels than the control group
      (190 +/- 68 MUmol/L and 477 +/- 128 MUmol/L vs 29 +/- 7 MUmol/L, P<0.01), and the
      severe AKI group had a significantly higher serum creatinine level than the mild
      AKI group (P<0.01). The tubulointerstitial damage score was significantly lower
      in the mild AKI group than in the severe AKI group (10.4 +/- 1.7 vs 14.0 +/- 1.5;
      P<0.05). The mild and severe AKI groups had significantly smaller areas of
      claudin-2 expression than the control group (5.0 +/- 0.5% and 3.7 +/- 0.7% vs 8.0
      +/- 0.7%; P<0.01), and the severe AKI group had a significantly smaller area of
      claudin-2 expression than the mild AKI group (P<0.01). The area of claudin-2
      expression was negatively correlated with serum creatinine level and
      tubulointerstitial damage score (r=-0.809 and -0.903; P<0.01). CONCLUSIONS: There
      are changes in the distribution and expression of claudin-2 in proximal tubular
      epithelial cells among children with AKI, and claudin-2 expression is closely
      related to renal pathological lesion and renal functional lesion.

PMID- 24750831
TI  - [Investigation and OCRL mutation analysis of a family with oculocerebrorenal
      syndrome of Lowe].
AB  - Oculocerebrorenal syndrome of Lowe (OCRL) is an X-linked recessive disorder. This
      study investigated the history of a Chinese family with OCRL and used direct DNA
      sequencing to screen all exons of OCRL gene for mutations. A missense mutation
      (1736 A->G) in exon 15 was revealed, which resulted in the change of His (H) 507
      to Arg (R). The patient's mother was the carrier of the heterozygous mutation in
      X-chromosome. To our knowledge, H507R mutation in OCRL gene has not been reported
      in Chinese people.

PMID- 24750832
TI  - [Expression of leukocyte-associated Ig-like receptor-1 in children with immune
      thrombocytopenia].
AB  - OBJECTIVE: To study the expression of leukocyte-associated Ig-like receptor
      1(LAIR-1) in children with immune thrombocytopenia (ITP), in order to explore the
      possible role of LAIR-1 in the pathogenesis of childhood ITP. METHODS: Expression
      levels of LAIR-1 on CD4(+) T cells, CD8(+) T cells and CD19(+)CD20(+) B cells of
      peripheral blood were measured in 40 children with ITP by flow cytometry. Serum
      level of solubility LAIR-1 (sLAIR-1) was measured using ELISA. Real-time PCR was
      used to measure LAIR-1 mRNA expression. Thirty-two healthy children served as the
      control group. RESULTS: The percentages of CD19(+)CD20(+) B cells in the ITP
      group were significantly higher than in the control group (P<0.05). In contrast,
      the percentage of CD4(+) T cells in the ITP group was significantly lower than in
      the control group (P<0.05). The expression levels of LAIR-1 on CD4(+) T cells and
      CD8(+) T cells were significantly lower in the ITP group than in the control
      group (P<0.05). Serum sLAIR-1 level and LAIR-1 mRNA expression in the ITP group
      significantly increased compared with the control group (P<0.05). CONCLUSIONS:
      LAIR-1 expression on CD4(+) and CD8(+) T cells decreases and serum sLAIR-1 level
      increases in children with ITP, suggesting that LAIR-1 may play an important role
      in immune imbalance in these children.

PMID- 24750833
TI  - [Telomere length and telomerase mutations in peripheral blood leukocytes of
      children with chronic aplastic anemia].
AB  - OBJECTIVE: To investigate the change in telomere length and TERC and TERT
      mutations in peripheral blood leukocytes of children with chronic aplastic anemia
      (CAA). METHODS: Sixty-nine children with CAA were divided into untreated group
      (n=24) who did not receive immunosuppressive therapy (IST), response group (n=36)
      who showed response to IST, and non-response group (n=9) who showed no response
      to IST; another 35 healthy children matched for age and sex were selected as the
      control group. The telomere-to-single copy gene (T/S) ratio in peripheral blood
      leukocytes was measured by real-time PCR in all groups. PCR was performed to
      detect TERC and TERT mutations in all children with CAA. RESULTS: The untreated
      and non-response groups had significantly lower T/S ratios than the control and
      response groups (P<0.01), whereas there was no significant difference in T/S
      ratio between the response and control groups (P>0.05). TERC and TERT mutations
      were not found in all children with CAA. CONCLUSIONS: The change in telomere
      length in children with CAA may be related to the development and progression of
      disease. Telomere length measurement may be used as a prognostic indicator in
      children with CAA.

PMID- 24750834
TI  - [Diagnostic values of neopterin and S100b for central nervous system infections
      in children].
AB  - OBJECTIVE: To study the diagnostic values of cerebrospinal concentrations of
      neopterin (NPT) and S100b for central nervous system infections in children.
      METHODS: Enzyme-linked immunosorbent assay was used to determinate the
      cerebrospinal concentrations of NPT and S100b in children with central nervous
      system infections and control children. The two groups of children were compared
      in terms of the two indicators, and the diagnostic values of the two indicators
      were evaluated by ROC curve analysis. RESULTS: Children with viral encephalitis
      had significantly increased cerebrospinal concentrations of NPT and S100b
      compared with the control group and children with purulent meningitis (P<0.01);
      there was no difference in the cerebrospinal concentration of NPT between
      children with purulent meningitis and the control group, while the concentration
      of S100b in the purulent meningitis group was significantly higher than in the
      control group (P<0.01). According to the ROC curves, S100b was more valuable than
      NPT in the diagnosis of viral encephalitis; when cerebrospinal concentration was
      more than 0.384 ng/mL, S100b had a sensitivity of 93.3% and a specificity of
      97.9%; a combination of the two indicators had a higher diagnostic value for
      viral encephalitis, with a sensitivity of 96.7% and a specificity of 97.9%.
      CONCLUSIONS: Both NPT and S100b have certain values in the diagnosis of central
      nervous system infections in children, and S100b is better than NPT.

PMID- 24750835
TI  - [Levels and prognostic significance of serum procalcitonin and D-dimer in
      children with systemic inflammatory response syndrome].
AB  - OBJECTIVE: To evaluate the prognostic significance of serum levels of
      procalcitonin (PCT) and D-dimer in children with systemic inflammatory response
      syndrome (SIRS). METHODS: A prospective case control study was conducted on 67
      pediatric patients with SIRS who were treated in the pediatric intensive care
      unit (PICU). Based on the presence or absence of infectious lesions, patients
      were categorized as sepsis and non-sepsis. Within 24 hours after admission, white
      blood cell (WBC) count and serum levels of PCT, C-reactive protein (CRP) and D
      dimer were determined, and the pediatric critical illness score (PCIS) was
      calculated. The correlation of PCIS with each of the other measurements was
      analyzed. On day 28 of follow-up, receiver operator characteristic (ROC) curve
      was plotted, and the area under ROC (AUC) was calculated. 28-day survival was
      estimated. Multivariate logistic regression analysis was performed to identify
      independent risk factors for in-hospital mortality. RESULTS: Serum levels of PCT
      and D-dimer were significantly higher (P<0.05) but PCIS was significantly lower
      (P<0.05) in patients with sepsis than in those without sepsis. Both PCT and D
      dimer were negatively correlated with PCIS (P<0.01). Serum levels of PCT and D
      dimer 24 hours after admission were higher (P<0.05) and PCIS was lower (P<0.05)
      in non-survivors than in survivors on day 28. AUC was 0.875, 0.872 and 0.863
      respectively for PCT, D-dimer and PCIS in the prediction of 28-day survival
      (P<0.01). Logistic regression analysis revealed that PCT and D-dimer were
      independent prognostic factors (odd ratio: 1.684 and 1.003; P<0.01). CONCLUSIONS:
      Serum levels of PCT may be helpful in differentiating sepsis and non-sepsis at
      early stage of SIRS in children. PCT and D-dimer are independent risk factors for
      in-hospital mortality in children with SIRS, and thus have a prognostic
      significance in clinical settings.

PMID- 24750836
TI  - [The role of endogenous vascular elastase in coronary artery reconstruction in
      Kawasaki disease].
AB  - OBJECTIVE: To investigate the role of endogenous vascular elastase (EVE) in
      coronary artery between reconstruction among pediatric patients with Kawasaki
      disease (KD). METHODS: Sixty children who were diagnosed with KD between January
      2012 and April 2013 were selected as the case group, and peripheral venous blood
      samples were collected on days 0-11 (pathological stage I) and days 12-25
      (pathological stage II) after the onset of disease; another 60 children without
      KD who visited the hospital due to acute fever during the same period were
      selected as the control group, and fasting peripheral venous blood samples were
      collected in the acute stage of fever. For both groups, serum levels of EVE and
      interleukin-6 (IL-6) and plasma vascular endothelial growth factor (VEGF) level
      were measured by enzyme-linked immunosorbent assay. For the case group,
      ultrasonic cardiography was used to detect coronary artery lesions (CALs) at the
      first, second and fourth weekends. The correlations of EVE level with IL-6 and
      VEGF levels were evaluated by Pearson correlation analysis. RESULTS: Serum levels
      of EVE and IL-6 in the case group in pathological stages I and II were
      significantly higher than in the control group (P<0.05), but plasma VEGF levels
      in stages I and II were significantly lower than in the control group (P<0.05);
      in the case group, EVE and IL-6 levels were significantly higher in stage II than
      in stage I (P<0.05). In pathological stage II, KD patients with CALs had
      significantly higher serum levels of EVE and IL-6 but significantly lower plasma
      VEGF levels compared with those without CALs (P<0.05); KD patients with coronary
      artery aneurysms (CAAs) had significantly higher serum levels of EVE and IL-6 but
      significantly lower plasma VEGF level compared with those without CAAs (P<0.05
      for all). EVE level was positively correlated with IL-6 level (r=0.915, P<0.05),
      yet negatively correlated with VEGF level (r=-0.769, P<0.05). CONCLUSIONS: EVE
      may participate in coronary artery reconstruction in children with KD. To
      interfere EVE activity may reduce and prevent CALs.

PMID- 24750837
TI  - [Clinical features and MECP2 mutations in children with Rett syndrome].
AB  - OBJECTIVE: To study the clinical features and mutations in methyl-CpG-binding
      protein 2 (MECP2) gene among children with classical Rett syndrome in China.
      METHODS: PCR and direct sequencing were employed to analyze the three exons of
      MECP2 gene in 9 children recently diagnosed with Rett syndrome and their parents.
      RESULTS: Heterozygous mutations were identified in 5 out of 9 patients, with a
      mutation rate of over 50%; there was one case of insert mutation (c.913insT) and
      4 cases of missense mutation (exon 3: c.316C>T (R106W); exon 4: c.502C>T (R168X),
      c.808C>T (R270X), and c.1126C>T (P376S). A new mutation (c.913insT) was found. No
      mutations were detected in their parents. Two patients had MECP2 mutations in the
      transcriptional repression domain (TRD). They had almost lost language functions
      and were found to have significantly delayed development compared with other
      patients. CONCLUSIONS: Mutations in MECP2 gene were detected in 5 confirmed cases
      of Rett syndrome, and most of them were on exon 4. Mutations in the TRD of MECP2
      protein may affect the language ability and development in children with Rett
      syndrome.

PMID- 24750838
TI  - [Clinical efficacy of letrozole in boys with idiopathic central precocious
      puberty].
AB  - OBJECTIVE: To investigate the efficacy of letrozole for delaying bone maturation
      and increasing predicted adult height in boys with idiopathic central precocious
      puberty (ICPP) who have a bone age above 13 years and a short stature, and its
      adverse effects. METHODS: Twenty ICPP boys with a bone age above 13 years and a
      short stature were randomly divided into letrozole treatment (n=10) and control
      groups (n=10). The letrozole treatment group received oral letrozole [2.5
      mg/(m(2).d), Qd] for 6 months, while the control group received no treatment and
      was observed periodically. Bone age, growth rate, height standard deviation (SD)
      score, predicted adult height SD score, sexual maturity, and levels of follicle
      stimulating hormone (FSH), luteinizing hormone (LH), dehydroepiandrosterone,
      testosterone (T), estradiol (E2), progesterone (P), and androstenedione (ASD)
      were measured. The letrozole-related adverse reactions were evaluated. RESULTS:
      After 6 months of treatment, both groups had a significantly increased bone age,
      but the letrozole group had a significantly slowed increase in bone age compared
      with the control group (13.82 +/- 0.23 years vs 14.47 +/- 0.30 years; P<0.05);
      compared with the control group, the letrozole group had a significantly
      increased predicted adult height SD score (-1.69 +/- 0.26 vs -1.91 +/- 0.35;
      P<0.05) and a significantly increased T level (4.9 +/- 0.9 nmol/L vs 4.4 +/- 0.8
      nmol/L; P<0.05). There was no significant difference in testicular volume between
      the two groups. The treatment led to no significant changes in growth rate,
      Tanner stage, and levels of FSH, LH, P, E2 and ASD in the two groups, and there
      was no significant difference in these indices between the two groups. No adverse
      reactions were observed during letrozole treatment. CONCLUSIONS: Letrozole delays
      bone maturation and increases predicted adult height in ICPP boys with a bone age
      above 13 years and a short stature, and it causes no obvious adverse reactions.

PMID- 24750839
TI  - [Clinical efficacy of adjuvant therapy with glucocorticoids in children with
      lobar pneumonia caused by Mycoplasma pneumoniae].
AB  - OBJECTIVE: To study the clinical efficacy of adjuvant therapy with
      glucocorticoids in children with lobar pneumonia caused by Mycoplasma pneumoniae.
      METHODS: One hundred and eight children with lobar pneumonia caused by Mycoplasma
      pneumoniae were randomly divided into routine treatment and hormone treatment
      groups. Both groups were treated with azithromycin and other symptomatic
      therapies. In addition to the basic treatment, the hormone treatment group was
      given dexamethasone 0.25-0.3 mg/(kg.d) by intravenous drip until the body
      temperature was normal. Then given oral prednisone tablets 0.5-1 mg/(kg.d)
      (gradually reduced) for a total treatment course of 7-10 days. Before and after
      treatment pulmonary functions were examined, and serum C-reactive protein (CRP),
      erythrocyte sedimentation rate (ESR), interleukin-2 (IL-2) and interleukin-6 (IL
      6) were measured. RESULTS: The duration of fever, cough relief time and pulmonary
      shadow absorption time on chest X-ray were significantly shorter in the hormone
      treatment group than in the routine treatment group (P<0.05). After treatment,
      the two groups showed improvements in serum CRP, ESR, IL-2, and IL-6 (P<0.05),
      but the hormone treatment group showed significantly more improvement (P<0.05).
      Varying degrees of mixed ventilation dysfunction were seen in the two groups
      before treatment, and hormone therapy significantly improved pulmonary function,
      especially promoting the recovery of small airway function. CONCLUSIONS: Adjuvant
      therapy with glucocorticoids can effectively alleviate clinical symptoms, promote
      the absorption of pulmonary inflammation, and improve pulmonary function in
      children with lobar pneumonia caused by Mycoplasma pneumoniae.

PMID- 24750840
TI  - [Viral etiology in children with acute lower respiratory tract infections plus
      platelet disorders in Changsha, China: an analysis of 255 cases].
AB  - OBJECTIVE: To investigate the viral etiology in hospitalized children with acute
      lower respiratory tract infections (ALRTI) plus platelet disorders. METHODS: A
      total of 255 children with ALRTI plus platelet disorders and 442 children with
      ALRTI and normal platelets, all of whom were hospitalized between March 2010 and
      February 2011, were included in the study. Their nasopharyngeal aspirate samples
      were collected, and RT-PCR or PCR was performed to detect 14 viruses. RESULTS: Of
      255 ALRTI patients with platelet disorders, thrombocytosis was found in 253 cases
      (99.2%) and thrombocytopenia in 2 cases (0.8%). Among ALRTI patients with
      platelet disorders, 173 (67.8%) were infected with at least one virus, with human
      rhinovirus as the most common one, followed by parainfluenza virus type 3 (PIV3)
      and respiratory syncytial virus (RSV). The detection rate of PIV3 in the abnormal
      platelet group was significantly higher than in the normal platelet group
      (P<0.05). In contrast, the detection rate of influenza virus B (IFVB) in the
      abonormal platelet group was significantly lower than in the normal platelet
      group (P<0.05). The age distribution showed significant difference between the
      abnormal and normal platelet groups (P<0.01). Platelet disorders were mainly
      found in children under one year of age (P<0.01). CONCLUSIONS: Thrombocytosis is
      often found in children with ALRTI caused by viruses, especially PIV3, but
      infection with IFVB seldom causes platelet disorders. Hospitalized children with
      ALRTI under one year tend to develop platelet disorders.

PMID- 24750841
TI  - [Clinical features of tracheobronchial foreign bodies in children].
AB  - OBJECTIVE: To investigate the clinical features of tracheobronchial foreign
      bodies in children and to provide a basis for feasible preventive measures.
      METHODS: A retrospective analysis was performed on the clinical data of 114
      children with tracheobronchial foreign bodies confirmed by fiberoptic
      bronchoscopy between February 2012 and February 2013. RESULTS: The majority
      (71.9%) of children with tracheobronchial foreign bodies were younger than three
      years old, and the male-to-female ratio was 2:l. The proportion of cases in
      winter was higher than that in summer. The incidence of tracheobronchial foreign
      bodies was significantly higher among rural children than among urban children.
      The positive rate of CT varied significantly for tracheobronchial foreign bodies
      at different sites, and the patients with tracheal foreign bodies had a
      significantly lower positive rate of chest CT than patients with foreign bodies
      in the left and right main bronchi (P<0.01). The misdiagnosis rate in children
      with a history of aspiration of foreign bodies was significantly lower than in
      children without one (P<0.01). CONCLUSIONS: Health education related to the
      prevention of tracheobronchial foreign bodies in children should be conducted
      primarily in rural areas. Tracheobronchial foreign bodies are common in children
      younger than three years old. Bronchoscopy should be performed early for
      suspected cases of tracheobronchial foreign bodies.

PMID- 24750842
TI  - [Perinatal high-risk factors for necrotizing enterocolitis in preterm infants: a
      case-control study].
AB  - OBJECTIVE: To study the timing of presentation and perinatal high-risk factors
      for necrotizing enterocolitis (NEC) in preterm infants with a gestational age of
      <33 weeks. METHODS: A case-control study was conducted in 49 preterm infants with
      NEC (gestational age <33 weeks) who were admitted to the Neonatal Intensive Care
      Unit of Beijing Bayi Children's Hospital between October 1, 2010 and December 30,
      2012, as well as preterm infants without NEC during the same period. The timing
      of presentation of NEC was retrospectively analyzed, and the perinatal high-risk
      factors for NEC were determined by multivariate logistic regression analysis.
      RESULTS: The median age of onset was 17.5 days (range: 3-106 d) in preterm
      infants with NEC. Sex, being small for gestational age, delivery mode and
      antenatal corticosteroid therapy were not associated with the development of NEC;
      low gestational age, low birth weight and neonatal asphyxia increased the risk of
      NEC, and low gestational age was identified as an independent high-risk factor
      for the development of NEC. CONCLUSIONS: Low gestational age is an important risk
      factor for the development NEC in preterm infants under 33 weeks' gestation, and
      the median age of onset is 17.5 days.

PMID- 24750843
TI  - [Temporal regulation of transcription factor Mef2c by histone acetylases during
      cardiogenesis].
AB  - OBJECTIVE: To observe the temporal modification of transcription factor Mef2c by
      histone acetylases (HATs) P300, PCAF, and SRC1 during cardiogenesis and to
      provide a basis for investigating the pathogenesis of congenital heart disease.
      METHODS: The normal heart tissues from embryonic mice (embryonic days 14.5 and
      16.5) and neonatal mice (postnatal days 0.5 and 7) were collected. The binding of
      P300, PCAF, and SRC1 to Mef2c gene and level of histone H3 acetylation in the
      promoter region of Mef2c were evaluated by chromatin immunoprecipitation assays.
      Meanwhile, real-time PCR was used to measure the mRNA expression of Mef2c.
      RESULTS: P300, PCAF, SRC1 were involved in histone acetylation in the promoter
      region of Mef2c during cardiogenesis in mice, and binding of P300, PCAF, and SRC1
      to the promoter of Mef2c varied significantly in different stages of
      cardiogenesis (P<0.01). The level of histone H3 acetylation and mRNA expression
      of Mef2c in the promoter region of Mef2c also varied significantly in different
      stages of cardiac development (P<0.01). The levels of acetylated H3, Mef2c mRNA,
      and HATs (P300, PCAF, SRC1) changed over time. They were highest on embryonic day
      14.5 (P<0.01), decreased gradually with cardiac development, and were maintained
      at low levels after birth. CONCLUSIONS: The mRNA expression of Mef2c varies
      during cardiogenesis in mice, which indicates that Mef2c plays an important role
      in the process of cardiac development. Meanwhile, histone acetylation in the
      promoter region of Mef2c is regulated temporally by HATs P300, PCAF, and SRC1.

PMID- 24750844
TI  - [Effect of emodin on expression of farnesoid X receptor in rats with acute
      cholestatic hepatitis].
AB  - OBJECTIVE: To investigate the expression of farnesoid X receptor (FXR) and the
      effect of emodin on FXR expression in a rat model of acute cholestatic hepatitis.
      METHODS: Ninety adult Sprague-Dawley rats were randomly divided into normal
      control, model, and emodin groups (n=30 each). The model and emodin groups were
      given alpha-naphthylisothiocyanate (ANIT) 50 mg/kg by gavage to establish an
      animal model of cholestatic hepatitis, while the normal control group was given
      an equal volume of sesame oil. The emodin group was given emodin by gavage every
      day from 4 days before the model was prepared until the time of sacrifice, while
      the model and normal control groups were given an equal volume of sodium
      carboxymethyl cellulose solution. At 24, 48 and 72 hours after the model was
      prepared, serum level of total bilirubin (TB), direct bilirubin (DB), alanine
      aminotransferase (ALT), and total bile acids (TBA) were measured by Aeroset
      automatic biochemical analyzer, and the mRNA expression of FXR in the liver
      tissue was measured by real-time PCR. RESULTS: At all time points FXR mRNA
      expression in the model group decreased, but serum levels of TB, DB, ALT and TBA
      increased significantly compared with the normal control group (P<0.05). The
      emodin group had significantly higher mRNA expression of FXR and significantly
      lower serum levels of TB, DB, ALT, and TBA compared with the model group
      (P<0.05). CONCLUSIONS: Emodin can significantly reduce serum levels of TB, DB,
      ALT, and TBA in rats with ANIT-induced cholestatic hepatitis, probably by
      promoting FXR expression.

PMID- 24750845
TI  - [A case report of infant hepatitis syndrome caused by cholelithiasis].

PMID- 24750846
TI  - [Anti-N-methyl-D-aspartate receptor encephalitis: a case report of an over 2-year
      old girl].

PMID- 24750847
TI  - [Fulminant type 1 diabetes in a child].

PMID- 24750848
TI  - Molecular investigation of tularemia outbreaks, Spain, 1997-2008.
AB  - Tularemia outbreaks occurred in northwestern Spain in 1997-1998 and 2007-2008 and
      affected >1,000 persons. We assessed isolates involved in these outbreaks by
      using pulsed-field gel electrophoresis with 2 restriction enzymes and multilocus
      variable number tandem repeat analysis of 16 genomic loci of Francisella
      tularensis, the cause of this disease. Isolates were divided into 3 pulsotypes by
      pulsed-field gel electrophoresis and 8 allelic profiles by multilocus variable
      number tandem repeat analysis. Isolates obtained from the second tularemia
      outbreak had the same genotypes as isolates obtained from the first outbreak.
      Both outbreaks were caused by genotypes of genetic subclade B.Br:FTNF002-00,
      which is widely distributed in countries in central and western Europe. Thus,
      reemergence of tularemia in Spain was not caused by the reintroduction of exotic
      strains, but probably by persistence of local reservoirs of infection. 

PMID- 24750849
TI  - Benign neonatal sleep myoclonus: our experience of 15 Japanese cases.
AB  - PURPOSE: Benign neonatal sleep myoclonus is a non-epileptic movement disorder
      that may mimic neonatal seizures. The aim of this study was to clarify the
      clinical manifestations and outcomes in Japanese infants with benign neonatal
      sleep myoclonus. METHODS: We reviewed the clinical manifestations and outcomes in
      15 consecutive patients with benign neonatal sleep myoclonus (males: 10),
      including three paired familial cases, referred to our center between 1996 and
      2011. The diagnosis of benign neonatal sleep myoclonus was based on a neonatal
      onset, characteristic myoclonic jerks that occurred during sleep, and normal
      electroencephalogram findings. RESULTS: All were healthy full-term neonates at
      birth. The age at onset ranged from 1 to 18 days (median: 7 days). Prior to
      referral to our center (3-8 weeks), two infants had been placed on antiepileptic
      drugs, without effects. During the clinical course, the myoclonic jerks resolved
      by 6 months in 14 of the 15 patients. On follow-up (final evaluation, mean: 38
      months), all but one patient (speech delay) showed normal development. None
      developed epilepsy. Of note, migraine occurred after 5 years of age in three
      children, including one who developed cyclic vomiting syndrome, evolving to
      migraine. Another boy developed cyclic vomiting syndrome, a precursor of
      migraine, before 1 year, and was being followed. A high incidence of migraine was
      observed in five (42%) of 12 parents whose detailed family history was available.
      CONCLUSION: Our study suggests that benign neonatal sleep myoclonus is related to
      migraine. With the high rate of familial cases, further genetic study, including
      migraine-related gene analysis, is necessary to determine the underlying
      mechanism responsible for benign neonatal sleep myoclonus.

PMID- 24750850
TI  - Aquaporin-4 autoimmunity in a child without optic neuritis and myelitis.
AB  - Neuromyelitis optica (NMO) is an inflammatory demyelinating disease with a poor
      prognosis that is characterized by inflammatory optic neuritis and myelitis.
      Although it is commonly misdiagnosed as multiple sclerosis (MS), distinguishing
      NMO from MS is important, as therapeutic approaches approved for MS are
      ineffective in patients with NMO. The aquaporin-4 (AQP4) antibody is a pathogenic
      and diagnostic biomarker for NMO. We report an AQP4 antibody-positive 9-year-old
      female with intractable hiccups and nausea (IHN). Brain imaging revealed lesions
      in the brainstem, thalami, and hypothalamus. Nevertheless, she had no clinical or
      radiological signs referable to the optic nerve or spinal cord. We propose that
      in patients with characteristic IHN associated lesions involving the brainstem or
      hypothalamus, measurement of AQP4 antibody should be considered for selectivity
      of treatment, even if the patient has no optic nerve or spinal cord lesions.

PMID- 24750851
TI  - Evaluation of the effects of single-nucleotide polymorphisms in CYP3A4 and CYP4F2
      on stable phenprocoumon and acenocoumarol maintenance doses: comment.

PMID- 24750852
TI  - Keloid of the circumcision scar: a rare complication.

PMID- 24750853
TI  - Yttrium-90 radioembolization vs sorafenib for intermediate-locally advanced
      hepatocellular carcinoma: a cohort study with propensity score analysis.
AB  - BACKGROUND & AIMS: Sorafenib and transarterial (90) Y-radioembolization (TARE)
      are possible treatments for Barcelona Clinic Liver Cancer (BCLC) intermediate
      advanced stage hepatocellular carcinoma (HCC). No study directly comparing
      sorafenib and TARE is currently available. This single-centre retrospective study
      compares the outcomes achieved with sorafenib and TARE in HCC patients
      potentially amenable to either therapy. METHODS: Seventy-four sorafenib (71 +/-
      10 years, male 87%, BCLC B/C 53%/47%) and 63 TARE HCC patients (66 +/- 9 years,
      male 79%, BCLC B/C 41%/59%) were included based on the following criteria: Child
      Pugh class A/B, performance status <=1, HCC unfit for other effective therapies,
      no metastases and no previous systemic chemotherapy. RESULTS: Median overall
      survivals of the two groups were comparable, being 14.4 months (95% CI: 4.3-24.5)
      in sorafenib and 13.2 months (95% CI: 6.1-20.2) in TARE patients, with 1-, 2- and
      3-year survival rates of 52.1%, 29.3% and 14.7% vs 51.8%, 27.8% and 21.6%
      respectively. Two TARE patients underwent liver transplantation after successful
      down-staging. To minimize the impact of confounding factors on survival analysis,
      propensity model matched 32 patients of each group for median age, tumour gross
      pathology and the independent prognostic factors (portal vein thrombosis,
      performance status, Model for End Liver Disease). Even after matching, the median
      survival did not differ between sorafenib (13.1 months; 95% CI: 1.2-25.9) and
      TARE patients (11.2 months; 95% CI: 6.7-15.7), with comparable 1-, 2- and 3-year
      survival rates. CONCLUSIONS: In cirrhotic patients with intermediate-advanced or
      not-otherwise-treatable HCC, sorafenib and TARE provide similar survivals. Down
      staging allowing liver transplantation only occurred after TARE.

PMID- 24750854
TI  - Systemic antioxidants and lung function in asthmatics during high ozone season: a
      closer look at albumin, glutathione, and associations with lung function.
AB  - BACKGROUND: Asthma is a chronic airway inflammatory disease with episodic
      symptoms of wheezing, chest tightness, cough, and shortness of breath. High
      ambient ozone levels have been associated with increased airway inflammation and
      asthma morbidity in prior studies. Mechanisms underlying individual
      susceptibility to asthma exacerbations from poor air quality are not fully
      understood. OBJECTIVE: As part of a panel observational study, we hypothesized
      that systemic antioxidant ability and antioxidant status may be associated with
      more stable asthma during high ozone season. METHODS: A cross sectional study was
      performed to evaluate the antioxidant profile in systemic circulation and its
      associations with clinical parameters in asthmatics and healthy controls during
      three summers in Atlanta, Georgia. RESULTS: In this panel of individuals with and
      without asthma, we found that although systemic glutathione levels were not
      different between the groups, serum albumin was significantly lower in the
      asthmatic group. Albumin also significantly correlated with lung function
      (%FEV(1)) and asthma quality of life scores. In a subgroup tested, plasma reduced
      glutathione (GSH) levels were associated with worse airways obstruction.
      CONCLUSION: Antioxidants GSH and albumin may have a role in maintaining lung
      function and asthma stability during times of poor ambient air quality.

PMID- 24750855
TI  - Isolation, structure and bioactivities of the polysaccharides from Angelica
      sinensis (Oliv.) Diels: a review.
AB  - The root of Angelica sinensis (Oliv.) Diels, a well-known Chinese herbal
      medicine, has been used historically as a tonic, hematopoietic and anti
      inflammatory agent for thousands of years. Modern phytochemistry and
      pharmacological experiments have proved that polysaccharide is one of the major
      active ingredients in A. sinensis. It has been demonstrated that A. sinensis
      polysaccharides had various important biological activities, such as
      hematopoiesis, immunomodulation, antitumor, antioxidant, radioprotection and
      hypoglycemic activity. The purpose of the present review is to summarize previous
      and current references regarding extraction and purification techniques as well
      as structural characterization and biological activities of A. sinensis
      polysaccharides.

PMID- 24750856
TI  - Chitosan, hyaluronan and chondroitin sulfate in tissue engineering for cartilage
      regeneration: a review.
AB  - Injection of hyaluronan into osteoarthritic joints restores the viscoelasticity,
      augments the flow of joint fluid, normalizes endogenous hyaluronan synthesis, and
      improves joint function. Chitosan easily forms polyelectrolyte complexes with
      hyaluronan and chondroitin sulfate. Synergy of chitosan with hyaluronan develops
      enhanced performances in regenerating hyaline cartilage, typical results being
      structural integrity of the hyaline-like neocartilage, and reconstitution of the
      subchondral bone, with positive cartilage staining for collagen-II and GAG in the
      treated sites. Chitosan qualifies for the preparation of scaffolds intended for
      the regeneration of cartilage: it yields mesoporous cryogels; it provides a
      friendly environment for chondrocytes to propagate, produce typical ECM, and
      assume the convenient phenotype; it is a good carrier for growth factors; it
      inactivates metalloproteinases thus preventing collagen degradation; it is
      suitable for the induction of the chondrogenic differentiation of mesenchymal
      stem cells; it is a potent means for hemostasis and platelet delivery.

PMID- 24750857
TI  - Piroxicam loaded alginate beads obtained by prilling/microwave tandem technique:
      morphology and drug release.
AB  - This paper presents a tandem technique, based on the combination of prilling and
      microwave (MW) assisted treatments, to produce biodegradable alginate carriers of
      piroxicam with different drug controlled release behaviours. Results showed that
      alginate/piroxicam beads demonstrated high encapsulation efficiency and very
      narrow dimensional distribution. Beads dried by MW retained shape and size
      distribution of the hydrated particles while drying rate was strongly increased
      compared to convective drying processes. Moreover, different MW irradiation
      regimes promoted interactions between the drug and alginate matrix, affected drug
      polymorphism as well as inner and surface matrix structure leading to different
      piroxicam release profiles. High level MW irradiation led to beads with highly
      porous and swellable matrix able to release piroxicam in few minutes in the
      intestine while convective drying produced gastro-resistant beads that exhibit
      sustained piroxicam release (total release in 5.5h) in intestinal environment. On
      these results the tandem technique prilling/MW irradiation appears to be
      promising to obtain alginate carrier with tailored NSAIDs release depending on
      drug characteristics and MW irradiation. 

PMID- 24750858
TI  - Structural investigation of a glycoprotein from gum ghatti.
AB  - The glycoprotein structure of gum ghatti was investigated. The covalent bonding
      between polysaccharides and proteins was firstly confirmed by high performance
      size exclusion chromatography (HPSEC) using refractive index (RI) and UV
      detectors. Partial acid hydrolysis and enzymatic degradation were also utilized.
      Several structural fragments such as AraHex2-HexA-HexNAc, Hex4HexNAc2,
      AraHex4HexNAc, Hex10HexNAc and Hex4HexNAc-Asn were identified from MALDI-TOF
      spectrum; using 1D and 2D NMR spectra, the linkage site of amino acids and
      polysaccharides was determined as N-linked (Hex)n-GlcNAc-Asn. Combined with the
      polysaccharide structure obtained before, a glycoprotein structure model was
      proposed. It was composed of 1,6-linked galactose backbone, which were attached
      by numerous of sugar side chains and peptide chains.

PMID- 24750859
TI  - Adhesion and micromechanical deformation processes in PLA/CaSO4 composites.
AB  - PLA/CaSO4 composites were prepared from uncoated and stearic acid coated filler
      particles in a wide composition range. The strength of interfacial adhesion was
      estimated quantitatively with three independent methods. Structure was
      characterized by DSC, XRD and SEM measurements, while mechanical properties by
      tensile and instrumented impact tests. The results proved that adhesion is twice
      as strong in composites prepared with the uncoated particles than in those
      containing the coated filler. Coating changes also local deformation processes
      around the particles. Although debonding is the dominating micromechanical
      deformation process in all composites, local plastic deformation is larger around
      coated particles. The extent of this deformation depends very much also on the
      local distribution of particles. The final properties and performance of the
      composites depend unambiguously on the micromechanical deformation processes
      occurring during loading, on debonding and the subsequent plastic deformation.
      Stearic acid used for the coating of the filler seems to dissolve in the polymer
      and locally change its properties. 

PMID- 24750860
TI  - Studies on the fibre surfaces modified with xylan polyelectrolytes.
AB  - Xylan was isolated from birch wood chips by using pressurized hot water
      extraction (PHWE). The extracted xylan was chemically modified yielding three
      different xylan derivatives (XDs): xylan sulfate (XS), carboxymethyl xylan (CMX)
      and xylan-4-[N,N,N-trimethylammonium]butyrate chloride (XTMAB). The structure and
      molecular weight of XDs was determined by using NMR spectroscopy and size
      exclusion chromatography (SEC). The potential utilization of xylan
      polyelectrolytes for modifying fibre surfaces was assessed by sorption
      experiments using bleached pine Kraft pulp as substrate. Polyelectrolyte
      titration method was chosen for estimating the amount of sorbed XDs onto the
      fibres. The cationic xylan derivative XTMAB had a strong interaction with fibres
      while the anionic derivatives did not show any sorption. X-ray photoelectron
      spectroscopy (XPS) and time of flight secondary ion mass spectrometry (ToF-SIMS)
      were selected as advanced surface analyses for studying the amount of surface
      anionic groups and the surface distribution of the XTMAB. XPS and polyelectrolyte
      titration results suggested that the XTMAB is sorbed onto the fibre surfaces. ToF
      SIMS imaging showed that XTMAB was evenly distributed on fibre surfaces.

PMID- 24750861
TI  - The effect of rice aging on the freeze-thaw stability of rice flour gels.
AB  - This study investigated the effect of aging rice on the freeze-thaw stability of
      rice flour gels since repeated freeze-thaw cycles can lead to reduced food
      quality. A rice grain cultivar called 'Khoa Dawk Mali 105' was aged for three
      different time periods, ranging from 0 to 12 months. Rice gels made from the aged
      rice were then freeze-thawed for up to 5 cycles. Repeated freeze-thaw cycles lead
      to an increase in syneresis values and hardness with increasing rice aging.
      Differential scanning calorimetry showed an increase in the enthalpy of melting
      of the amylose-lipid complex after 5 freeze-thaw cycles and an increase in peak
      gelatinization temperature and gelatinization enthalpy with longer rice aging.
      Moreover, aging length of the rice correlated significantly with a decrease in
      peak viscosity and breakdown but also an increase in final viscosity and setback.
      These results demonstrate that aging the rice reduced the freeze-thaw stability
      of the rice flour gels.

PMID- 24750862
TI  - Modification of cellulosic fibers to enhance their dyeability using UV
      irradiation.
AB  - Present research was proposed to evaluate the effect of UV radiation on the
      dyeing of cellulosic fabrics with direct dyes. The cellulosic fabric was
      irradiated by using UV radiation assembly (180 W) for different time intervals
      i.e., 30, 45, 60, 75 and 90 min respectively. The alike set of fabrics was
      prepared varying the concentration of NaOH during mercerization of the fabrics.
      All the treated fabrics were dyed with direct dyes. The dyeing parameters such as
      temperature, time, pH and salt concentration were optimized. The standard methods
      were employed to evaluate the color strength at various levels of pH,
      temperature, dyeing contact time and salt concentration. Scanning electron
      microscope test was performed in order to evaluate the change in fibril structure
      and surface. The obtained results of the dyed fabrics previously treated with UV
      radiation and after mercerization were compared. The results revealed that the
      color strength of UV-irradiated fabric was high as compared to mercerized
      cellulosic fabrics.

PMID- 24750863
TI  - Microwave-assisted solid-phase synthesis of pH-responsive polyaspartamide
      derivatives.
AB  - Biodegradable stimulus-responsive polymers have attracted more attention in
      biomedical fields. Here, a series of pH-responsive polyaspartamide derivatives
      are successfully synthesized from poly(N-substituted alpha/beta-asparagines) by a
      facile, solvent-free and catalyst-free microwave-assisted method. The polymer
      structure is confirmed by (1)H NMR, IR and UV-Vis spectra. With much shorter
      reaction time (13-18 min), the degree of substitution (DS) of the anhydride
      modified polyaspartamide derivatives obtained by microwave heating is two to
      three times higher as that obtained by conventional heating in DMF (24h). In
      addition, pH-induced phase transition behavior of polyaspartamide derivatives is
      investigated by dynamic light scattering (DLS). The critical pH transition (pHtr)
      of the resulted polymers increases with increasing DS of the polymers. The
      hydrophile-lipophile balance (HLB) of the obtained polymers is evaluated to study
      the relationship between pHtr and polymer structure.

PMID- 24750864
TI  - Chitosan microcapsules loaded with either miconazole nitrate or clotrimazole,
      prepared via emulsion technique.
AB  - In this paper, a simple and versatile coacervation technique has been developed
      by using an ultrasound-assisted oil/water emulsion method for the preparation of
      antifungal agent-loaded microcapsules. Two types of chitosan microcapsules are
      successfully prepared. The mean particle size of the chitosan/miconazole nitrate
      microcapsules is 2.6 MUm and that of the chitosan/clotrimazole microcapsules is
      4.1 MUm. The encapsulation efficiency of the chitosan/miconazole nitrate
      microcapsules (77.58-96.81%) is relatively higher than that of the
      chitosan/clotrimazole microcapsules (56.66-93.82%). The in vitro drug release
      performance of the microcapsules shows that the chitosan/miconazole nitrate
      microcapsules release about 49.5% of the drug while chitosan/clotrimazole
      microcapsules release more than 66.1% of the drug after 12h under a pressure of 5
      kg at pH 5.5, which is similar to the pH of human skin. The prepared drug-loaded
      microcapsules could be applied onto bandages or socks, and will continuously
      release antifungal drugs in a controlled manner under pressure.

PMID- 24750865
TI  - Quantification of crystalline cellulose in lignocellulosic biomass using sum
      frequency generation (SFG) vibration spectroscopy and comparison with other
      analytical methods.
AB  - The non-centrosymmetry requirement of sum frequency generation (SFG) vibration
      spectroscopy allows the detection and quantification of crystalline cellulose in
      lignocellulose biomass without spectral interferences from hemicelluloses and
      lignin. This paper shows a correlation between the amount of crystalline
      cellulose in biomass and the SFG signal intensity. Model biomass samples were
      prepared by mixing commercially available cellulose, xylan, and lignin to defined
      concentrations. The SFG signal intensity was found sensitive to a wide range of
      crystallinity, but varied non-linearly with the mass fraction of cellulose in the
      samples. This might be due to the matrix effects such as light scattering and
      absorption by xylan and lignin, as well as the non-linear density dependence of
      the SFG process itself. Comparison with other techniques such as XRD, FT-Raman,
      FT-IR and NMR demonstrate that SFG can be a complementary and sensitive tool to
      assess crystalline cellulose in biomass.

PMID- 24750866
TI  - Role of vacuum steps added before and after steaming treatment of maize starch.
      Impact on pasting, morphological and rheological properties.
AB  - Standard maize starch (SMS) was hydrothermally treated by three processes; DV-HMT
      (Direct Vapor-Heat Moisture Treatment), RP-HMT (Reduced-Pressurized Heat Moisture
      Treatment) and DIC (in French: Detente Instantanee Controlee, instantaneous
      controlled pressure drop). Impact of processes were studied in order to determine
      the role of added steps of vacuum before and after treatment of starch by live
      steam at different pressures (1, 1.5, 2, 2.5 and 3 bar) on morphological, pasting
      (Brabender) and rheological properties of SMS suspension. The three treatments
      tend to modify the physical properties of starch on the same way, but the extent
      of these modifications depends on the process and on the level presure applied.
      The intensity of modifications follows this order: DIC>RP-HMT>DV-HMT. This was
      attributed to the presence of the initial vacuum step (DIC and RP-HMT) which
      intensified the transfer phenomena and to the mechanical effect induced by the
      abrupt decompression towards vacuum (DIC) leading to weakness of starch granules.
      The treatments changed the shape and distribution size of granules. The sizes
      were shifted towards higher values after the treatment due both to the
      improvement of swelling capacity of granules and to the presence of agglomerates
      particles of different sizes as confirmed by scanning electron microscopy. The
      agglomerates glued together by gelatinized granules were favored by the direct
      contact of starch with steam during the treatments. The results showed for all
      treatments, a reduction of the consistency coefficient (k) and of the yield
      stress (tau0) of starch suspensions with increasing of process intensity. For
      severe conditions (3 bar), no difference between the treatments was observed; a
      complete fluidization of starch suspensions (the consistencies were too weak to
      be detected), tau0 vanished and the rheological behavior tended to a Newtonian
      type. Elastic modulus (G'), measured during gelation at 25 degrees C, decreased
      dramatically (G'<1 Pa), that revealed the loss of rigidity and disappearance of
      granular integrity of starch.

PMID- 24750867
TI  - Synthesis of superparamagnetic bare Fe3O4 nanostructures and core/shell
      (Fe3O4/alginate) nanocomposites.
AB  - In this article we report about the synthesis of superparamagnetic bare Fe3O4
      nanostructures and core/shell (Fe3O4/alginate) nanocomposites by simple low
      temperature based method at pH values 5, 9, and 14. The structural morphology and
      magnetic behavior of Fe3O4 nanostructures and core/shell (Fe3O4/alginate)
      nanocomposites (Fe3O4/alg NCs) have been investigated by X-ray diffractometer
      (XRD), Fourier transform infrared spectroscopy (FT-IR), Raman spectroscopy (RS),
      ultraviolet-visible (UV-vis) spectroscopy, transmission electron microscopy
      (TEM), energy dispersive X-ray spectroscopy (EDX) and vibrating sample
      magnetometer (VSM). The particle size was calculated by TEM measurements and it
      turns out to be ~10 nm and ~14 nm for bare Fe3O4 nanoparticle and Fe3O4/alg NCs
      with core/shell structure, respectively. The magnetic properties of the
      synthesized products were found to be function of pH at which the synthesis has
      been done. The synthesized Fe3O4 nanoparticle and Fe3O4/alg NCs were found to be
      superparmagnetic in nature at room temperature. We observed that the value of
      saturation magnetization in case of Fe3O4/alg NCs decreases by increasing the pH
      value.

PMID- 24750868
TI  - Synthesis of worm like silver nanoparticles in methyl cellulose polymeric matrix
      and its catalytic activity.
AB  - A facile one step method for the synthesis of wormlike silver nanoparticles has
      been carried out in methyl cellulose matrix. Synthesis is based on the reduction
      of AgNO3 by sodium borohydride (NaBH4) in aqueous methyl cellulose (MC).
      Synthesized nanoparticles are mostly mono disperse in size and their aggregation
      is controlled by varying the concentration of AgNO3. Silver nanoparticles are
      analyzed using transmission electron microscope (TEM), UV-vis spectroscopy and X
      ray diffraction (XRD) technique. It has been found that the concentration of
      AgNO3 has a significant effect on the morphology of Ag nanostructures. Worm like
      nanostructures showed excellent catalytic activity in the borohydride reduction
      of p-nitrophenol compared to spherical shaped nanoparticles.

PMID- 24750869
TI  - Discontinuous and heterogeneous glass transition behavior of carbohydrate polymer
      plasticizer systems.
AB  - In order to understand the glass transition properties of carbohydrate polymer
      plasticizer systems, glass transition temperatures of dextrin-glucose and dextrin
      maltose systems were investigated systematically using differential scanning
      calorimetry. The onset (Tg(on)) and offset (Tg(off)) of the glass transition
      decreased with increasing plasticizer (glucose or maltose) content, and showed an
      abrupt depression at certain plasticizer content. The abrupt depression of
      Tg(off) occurred at higher plasticizer content than that of Tg(on). The glass
      transition was much broader for intermediate plasticizer content. From the
      enthalpy relaxation behavior of samples aged at various temperatures, it was
      found that two different glass transitions occurred contentiously in the broad
      glass transition. These results suggested that carbohydrate polymer-plasticizer
      systems can be classified into three regions: the entrapment of the plasticizer
      by the polymer, the formations of the polymer-plasticizer and plasticizer-rich
      domains, and the embedment of polymer into the plasticizer.

PMID- 24750870
TI  - Chitosan-functionalized poly(methyl methacrylate) particles by spinning disk
      processing for lipase immobilization.
AB  - Chitosan-functionalized poly(methyl methacrylate) (PMMA-CH) particles were
      prepared by complexation between the negatively charged PMMA particles and the
      positively charged chitosan via a spinning disk processing. Processing
      parameters; feed rate and spinning speed, were optimized, which were traced by
      size distribution profiles of the formed PMMA-CH particles. Their sizes and net
      surface charges were found to be affected by MWs of chitosan (45, 100, and 230
      kDa) used. Microscopic evidences were used to confirm their core-shell
      morphology. Chemical characteristics and thermal stability of such particles were
      determined by FTIR and TGA, respectively. Then, their ability to immobilize
      lipase (EC 3.1.1.3) was conducted and followed through zeta potential
      measurement. The percentage of lipase adsorption capacity increased with
      increasing lipase content, but the value decreased when the size of PMMA-CH
      particles increased. Also, the activity of lipase attached on PMMA-CH particles'
      surface was preserved and increased with lipase loading.

PMID- 24750871
TI  - Concept of heat-induced inkless eco-printing.
AB  - Existing laser and inkjet printers often produce adverse effects on human health,
      the recycling of printing paper and the environment. Therefore, this paper
      examines the thermogravimetry curves for printer paper, analyzes the
      discoloration of paper using heat-induction, and investigates the relationship
      between paper discoloration and the heat-inducing temperature. The mechanism of
      heat-induced printing is analyzed initially, and its feasibility is determined by
      a comparative analysis of heat-induced (laser ablation) printing and commercial
      printing. The innovative concept of heat-induced inkless eco-printing is
      proposed, in which the required text or graphics are formed on the printing paper
      via yellowing and blackening produced by thermal energy. This process does not
      require ink during the printing process; thus, it completely eliminates the
      aforementioned health and environmental issues. This research also contributes to
      related interdisciplinary research in biology, laser technology, photochemistry,
      nano-science, paper manufacturing and color science.

PMID- 24750872
TI  - Homogeneous and heterogeneous methods for laccase-mediated functionalization of
      chitosan by tannic acid and quercetin.
AB  - Homogeneous and heterogeneous methods for functionalization of chitosan with
      quercetin or tannic acid using laccase from Trametes versicolor is presented,
      yielding a bio-based product with synergistic antioxidant and antimicrobial
      properties. HPLC-SEC analysis and cyclic voltammetry kinetic studies showed that
      laccase catalyzes the oxidation of quercetin to electrophilic o-quinones, which
      undergo to an oligomer/polymer-forming structures. On the other hand, tannic acid
      was converted into gallic acid, its dimers, partially gallic acid esterified
      glucose and glucose, when exposed to laccases. ATR-FTIR spectroscopy provided
      evidence that quercetin o-quinones undergo coupling reactions with amino groups
      of chitosan via Schiff-base and Michael addition mechanisms under heterogeneous
      method, while oxidized tannic acid cross-linked with chitosan by hydrogen and
      electrostatic interactions under both methods. All polyphenols functionalized
      chitosans showed greatly improved ABTS(+) cation radicals scavenging capacity,
      compared with the untreated chitosan, while antimicrobial activities
      significantly depended on the mode of functionalization and type of
      microorganism. 

PMID- 24750873
TI  - Preparation of polysilsesquioxane-urethaneacrylate copolymer film reinforced with
      chitin nanofibers.
AB  - Chitin nanofibers (CNFs) reinforced silsesquioxane-urethaneacrylate (SSQ-UA)
      copolymer films were prepared. CNFs-SSQ-UA nanocomposite films were highly
      transparent due to the filling of nanometer sized (10-20 nm) CNFs inside the
      hybrid organic-inorganic SSQ-UA copolymer. CNFs due to their crystalline
      structure drastically increased Young's moduli and the tensile strengths of the
      composite and decreased the thermal expansion. High thermal stability of
      polysilsesquioxane improved heat resistance of CNFs.

PMID- 24750875
TI  - Graft polymers of eucalyptus lignosulfonate calcium with acrylic acid: synthesis
      and characterization.
AB  - The graft copolymerization of eucalyptus lignosulfonate calcium (HLS-Ca) from
      hardwood and acrylic acid (AA) was investigated by using Fenton agent as a
      coinitiator. The influences of reaction conditions on grafting parameters i.e.
      product yield (Y%), AA conversion (C%), grafting ratio (G%) and grafting
      efficiency (GE%) were carefully studied. The effects of the phenolic hydroxyl (Ph
      OH) group on the polymerization of AA and grafting reaction were researched.
      Graft copolymers were identified by the new absorption at 1,727 cm(-1), more
      homogenized morphology and higher decomposition temperature after grafted with
      AA, as illustrated in FTIR, SEM and TG spectra. The optimum synthesis conditions
      are as follows: H2O2=25.2 mol/L, FeCl2=63.0 mol/L, T=50 degrees C and t=2h and
      the optimum percentages of Y, C, G and GE are 97.61%, 95.23%, 71.29% and 78.85%,
      respectively. The Ph-OH group of HLS-Ca cannot inhibit the polymerization of AA
      and is involved in the grafting reaction as an active center.

PMID- 24750874
TI  - The protective effect of xanthan gum on interleukin-1beta induced rabbit
      chondrocytes.
AB  - We have previously shown that intra-articular injection of xanthan gum (XG) could
      protect the joint cartilage and reduce osteoarthritis progression. In this study,
      we investigated the preliminary cytotoxicity of XG on chondrocytes, evaluated the
      effects of XG on the proliferation and the protein expression of matrix
      metalloproteinases (MMPs), tissue inhibitors of metalloproteinase-1 (TIMP-1) in
      interleukin-1beta (IL-1beta)-induced rabbit chondrocytes. Primary rabbit
      chondrocytes were cultured. After treatment with various concentrations of XG
      with or without 10 ng/mL IL-1beta, the proliferation of chondrocytes was
      evaluated using the MTT assay and the expression levels of MMPs and TIMP-1 were
      evaluated using ELISA. The results showed that XG alone displayed no adverse
      effects on cell viability and reversed significantly IL-1beta-reduced cell
      proliferation in a dose-dependent manner. Furthermore, XG showed a dose-dependent
      inhibition in the IL-1beta-induced release of MMPs while increasing TIMP-1
      expression. These results strongly suggest that XG affords protection on IL-1beta
      induced rabbit chondrocytes.

PMID- 24750876
TI  - Structural characterization of natural ideal 6-O-sulfated agarose from red alga
      Gloiopeltis furcata.
AB  - A charge and size uniform polysaccharide GW2M was extracted with cold water from
      red alga Gloiopeltis furcata and purified by strong anion ion-exchange and gel
      permeation chromatography. Its chemical structure was identified by methylation,
      (1)H-(1)H COSY, (1)H-(13)C HMQC and (1)H-(13)C HMBC techniques. The experimental
      data showed that GW2M was composed of galactose (40.3%), 3,6-anhydro-galactose
      (34.1%) and sulfate (24.8%) with an average molecular mass of 20.6 kDa. The
      results proved GW2M was a linear repeating sequence of alternating (1->3)-linked
      6-O-sulfated-beta-d-galactose (G6S) and (1->4)-linked 3,6-anhydro-alpha-l
      galactose (A) which made it to be an ideal 6-O-sulfated-agarose. The sequences of
      serial oligosaccharides prepared by mild acid and reductive acid hydrolysis from
      GW2M were confirmed using electrospray collision induced dissociation tandem mass
      spectrometry (ES-CID-MS/MS) technique.

PMID- 24750877
TI  - Protective effect of a water-soluble polysaccharide from Salvia miltiorrhiza
      Bunge on insulin resistance in rats.
AB  - Oxidative stress is associated with insulin resistance (IR) and is thought to
      contribute to the development and progression toward type 2 diabetes (T2DM). This
      study was undertaken to isolate the bioactive polysaccharide (SMPW1) from Salvia
      miltiorrhiza Bunge and investigated its protective effects on IR model in rats
      induced by tert-butyl hydroperoxide (t-BHP). In vivo animal experiments showed
      that SMPW1 (50 and 100mg/kg) possessed high antioxidative and protective capacity
      against the injury induced by t-BHP, as reflected in the increased expression or
      activities of catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase
      (GPx), and the decreased formation of malondialdehyde (MDA) in serum and liver
      homogenates. In addition, SMPW1 (50 and 100mg/kg) also attenuated IR and the
      morphological injury of liver and pancreas induced by t-BHP, and improved insulin
      sensitivity index. In conclusion, SMPW1 can protect against the development of
      T2DM and improve IR via reduction of oxidative stress. 

PMID- 24750878
TI  - Interactions of cellulose-based comb polyelectrolyte with oppositely charged
      surfactant dodecyl-trimethylammonium bromide.
AB  - A comb ethyl cellulose-g-sodium polyacrylate (EC-g-SPA) was synthesized by atom
      transfer radical polymerization. The amphiphilic properties of the EC-g-SPA were
      determined by surface tension measurements. The interactions between EC-g-SPA and
      the cationic surfactant dodecyl-trimethylammonium bromide (C12TAB) were
      investigated by surface tension, turbidity, dynamic light scattering and
      transmission electron microscopy (TEM). The results revealed that the critical
      aggregate concentration (CAC) of the complexes was 0.8mM. When the C12TAB
      concentration was lower than the CAC, the hydrodynamic diameter (Dh) of the
      complexes decreased as the surfactant concentration was increased. As the C12TAB
      concentration was increased above the CAC, the Dh initially increased slightly,
      followed by a sharp decrease. The changes in the sizes and shapes of the
      aggregates were studied by TEM. The interactions between two species and the
      structure of the EC-g-SPA/C12TAB complexes were also discussed. 

PMID- 24750879
TI  - Silver nanoparticle-loaded PVA/gum acacia hydrogel: synthesis, characterization
      and antibacterial study.
AB  - A simple one-pot method for in situ synthesis of silver nanoparticles (AgNPs),
      within polyvinyl alcohol/gum acacia (PVA-GA) hydrogel matrix, by gamma radiation
      induced cross-linking is reported here. The synthesized hydrogels were
      characterized by FT-IR, thermogravimetry, dynamic light scattering and
      inductively coupled mass spectrometry method. The thermal stability was found to
      be more for the hydrogel loaded with silver nanoparticles and also the percentage
      silver loading was found to increase with increase in cross-linking density. The
      influence of gum acacia (GA) concentration on the equilibrium degree of swelling
      of the synthesized hydrogels, and also on the silver release from hydrogel
      matrix, was investigated. The size of the silver nanoparticles formed in the
      hydrogel matrix was in the range of 10-40 nm. The rheological gel point was found
      to be at 25.34 kGy of radiation dose, for a typical hydrogel synthesized, using
      5% GA, 3% PVA and 1mM AgNO3. The antibacterial studies of the synthesized
      nanosilver-containing hydrogels showed good antibacterial activity against gram
      negative bacterium, Escherichia coli.

PMID- 24750880
TI  - Structural and compositional characteristics of hybrid carrageenans from red
      algae Chondracanthus chamissoi.
AB  - Two polysaccharides CCC and CCH were extracted from red algae Chondracanthus
      chamissoi by cold water and hot water, respectively. Characterization of the
      structure by chemical and spectroscopic methods showed that CCC was a hybrid
      carrageenan composed of kappa-carrageenan (35%) and iota-carrageenan (43%) along
      with its precursor MU-carrageenan (22%) and CCH was an ideal kappa-carrageenan.
      Oligosaccharides from CCH and CCC were prepared and their structural sequences
      determined by ES-CID-MS/MS gave further insight into the structural
      characteristics of hybrid carrageenans from C. chamissoi. Some hybrid
      oligosaccharides, e.g., kappa-kappa, kappa-MU and kappa-iota, were obtained with
      mild acid hydrolysis of CCC. Then, a regular even-numbered oligosaccharides
      generated with reductive acid hydrolysis of CCH confirmed it an ideal kappa
      carrageenan.

PMID- 24750881
TI  - Preparation and properties of novel melt-blended halloysite nanotubes/wheat
      starch nanocomposites.
AB  - Novel bionanocomposites based on halloysite nanotubes as nanofillers and
      plasticized starch as polymeric matrix were successfully prepared by melt
      extrusion for the first time. Both modified and non modified halloysites were
      added at different weight contents. The structural, morphological, thermal and
      mechanical properties of plasticized starch/halloysites nanocomposites were
      investigated. Melt-compounding appears to be a suitable process to uniformly
      disperse nanotubes in the plasticized starch matrix. Interactions between
      plasticized starch and halloysites in the nanocomposites and microstructure
      modifications were monitored using Fourier transfer infrared spectroscopy, X-ray
      diffraction and dynamic mechanical analysis. Addition of halloysite nanotubes
      slightly enhances the thermal stability of starch (onset temperature of
      degradation delayed to higher temperatures). The tensile mechanical properties of
      starch are also significantly improved (up to +144% for Young's modulus and up to
      +29% for strength) upon addition of both modified and unmodified halloysites,
      interestingly without loss of ductility. Modified halloysites lead to
      significantly higher Young's modulus than unmodified halloysites.

PMID- 24750882
TI  - Media optimization for elevated molecular weight and mass production of pigment
      free pullulan.
AB  - In this study, an Aureobasidium pullulans SZU 1001 mutant, deficient in pigment
      production, was screened by complex UV and gamma-ray mutagenesis. Medium
      composition optimization for increased pullulan molecular weight and production
      was conducted using this mutant. Six nutrients: yeast extract, (NH4)2SO4, K2HPO4,
      NaCl, MgSO4.7H2O and CaCl2 were detected within pullulan production in flasks. It
      is shown that NaCl and K2HPO4 have significant influences on molecular weight of
      pullulan, while yeast extract and (NH4)2SO4 significantly affect pullulan yield.
      To achieve a higher molecular weight and more efficient pullulan production, a
      response surface methodology approach was introduced to predict an optimal
      nutrient combination. A molecular weight of 5.74 * 10(6) and pullulan yield on
      glucose of 51.30% were obtained under batch pullulan fermentation with the
      optimized media, which increased molecular weight and pullulan production by
      97.25% and 11.04%, respectively compared with the control media.

PMID- 24750883
TI  - In vitro characterisation of chitosan based xerogels for potential buccal
      delivery of proteins.
AB  - Chitosan and thiolated-chitosan based xerogels have been prepared by lyophilising
      aqueous gels of the polymers incorporating glycerol, d-mannitol and BSA with an
      annealing process. Analytical characterisation was by circular dichroism,
      infrared spectroscopy, X-ray diffraction and scanning electron microscopy.
      Swelling capacities of 1,110 +/- 23.3% and 480 +/- 18.2% were obtained for the
      chitosan and TG-chitosan xerogels respectively. Thiolation caused improved in
      vitro mucoadhesive properties by demonstrating peak adhesive force of 4.5 +/- 0.7
      and 5.8 +/- 0.2N, and total work of adhesion of 6.5 +/- 1.0 and 19 +/- 0.8 mJ for
      chitosan and thiolated-chitosan xerogels respectively. In vitro drug dissolution
      studies using Bradford's assay showed BSA release of 91.5 +/- 3.7% and 94.4 +/-
      7.3% from the chitosan and thiolated-chitosan xerogels respectively. These
      results demonstrate the potential of developing lyophilised thiolated-chitosan
      xerogels with optimised mucoadhesion characteristics for buccal mucosa delivery
      of protein based drugs.

PMID- 24750884
TI  - Isolation and antitumor activities of acidic polysaccharide from Gynostemma
      pentaphyllum Makino.
AB  - Two acidic polysaccharides (GP-B1 and GP-C1) were obtained from Gynostemma
      pentaphyllum. The molecular weights (Mw) of the two fractions were 79 kDa for GP
      B1 and 126 kDa for GP-C1. GP-B1 was composed of Gal, Ara, Man, Rha, Xyl, Glc,
      GalA and GlcA in a molar ration of 3.5:3.2:0.6:0.9:0.3:0.5:0.6:0.4. GP-C1
      consisted of Gal, Ara, Man, Rha, Glc, and GlcA in the proportions of
      2.1:1.0:0.3:0.5:0.4:0.9. Among them, GP-B1 treatment had a significant inhibitory
      effect on the growth of melanoma B16 in vivo and in vitro. Meanwhile GP-B1 could
      increase the relative spleen weight and stimulate the splenocyte proliferation
      alone or combined with ConA. Moreover, GP-B1 treatment induced an evident
      increase in the level of serum TNF-alpha, IFN-gamma, and IL-12 and a reduction
      for IL-10 production. These results indicate that the antitumor effects of GP-B1
      are associated with immunostimulation.

PMID- 24750885
TI  - Peptide-functionalized chitosan-DNA nanoparticles for cellular targeting.
AB  - Chitosan-pDNA nanoparticles with various weight ratios (chitosan:pDNA 1:4-8:1)
      were characterized for particle size, zeta potential, morphology, and pDNA
      binding efficiency. For targeted gene delivery applications, nanoparticles were
      functionalized by coupling fluorescent dye and tyrosine kinase receptor B (TrkB)
      binding peptides on the particle surface. The targetability of the peptide
      functionalized nanoparticles was demonstrated in TrkB positive murine transformed
      monocyte/macrophage cells (RAW 264). It was observed that weight ratio influenced
      DNA condensation and nanoparticle properties. An increase in the weight ratio
      decreased the average particle size, but increased the zeta potential. Cell
      culture studies showed that TrkB-peptide-functionalized nanoparticles bound to
      cells more effectively than nanoparticles functionalized with a control peptide.
      The length of the PEG spacer arm of the amine-to-sulfhydryl crosslinker used in
      the functionalization was found to positively correlate with the cellular
      attachment efficiency. This study suggests that the peptide-functionalization
      could be used to target chitosan-pDNA nanoparticles to specific cells.

PMID- 24750886
TI  - Compatibilization of starch-zein melt processed blends by an ionic liquid used as
      plasticizer.
AB  - An ionic liquid (1-butyl-3-methyl imidazolium chloride [BMIM]Cl) was used as a
      plasticizer in starch, zein and their blends; and compared to glycerol, a
      classical plasticizer of starch. Thermoplastic plasticized biopolymer materials
      were obtained by melt processing using a twin screw microcompounder. Such a
      device allows simulating a twin screw extrusion process on small batches of a few
      grams, and to evaluate the necessary specific mechanical energy input for native
      starch destructurization; and the final apparent melt viscosity. Both were shown
      to be significantly reduced for starch in presence of [BMIM]Cl (compared to
      glycerol), while zein processing behavior was less sensitive to the plasticizer
      used. This induces significant starch/zein viscosity ratio differences, which
      affect melt mixing of the starch zein blends. In starch rich blends, this results
      in smaller zein aggregates in the case of [BMIM]Cl. The characterization of the
      materials indicates that, compared to glycerol, the use of [BMIM]Cl leads to less
      hygroscopicity, a more efficient plasticization of both starch and zein phases
      and a compatibilization of starch/zein blends.

PMID- 24750887
TI  - Biodegradable and bioactive CGP/PVA film for fungal growth inhibition.
AB  - In this study, chitinolytic enzymes produced by Trichoderma asperellum were
      immobilized on a biodegradable film manufactured with a blend of cashew gum
      polysaccharide (CGP) and polyvinyl alcohol (PVA), and tested as a fungal growth
      inhibitor. The film was produced by casting a blend of CGP and PVA solution on
      glass molds. The CGP/PVA film showed 68% water solubility, tensile strength of
      23.7 MPa, 187.2% elongation and 52% of mass loss after 90 days in soil. The
      presence of T-CWD enzymes immobilized by adsorption or covalent attachment
      resulted in effective inhibition of fungal growth. Sclerotinia sclerotiorum was
      the most sensitive organism, followed by Aspergillus niger and Penicillium sp.
      SEM micrograph showed that the presence of immobilized T-CWD enzymes on CGP/PVA
      film produced morphological modifications on vegetative and germinative
      structures of the microorganisms, particularly hyphae disruption and changes of
      spores shape.

PMID- 24750888
TI  - Simultaneous improvement of mechanical properties and thermal stability of
      bacterial polyester by cellulose nanocrystals.
AB  - Green nanocomposites were prepared by adding well-dispersed cellulose
      nanocrystals (CNCs) into bacterial polyester poly(3-hydroxybutyrate-co-3
      hydroxyvalerate) (PHBV) matrix. Simultaneous enhancements on the mechanical
      property and thermal stability of PHBV after reinforcement of CNCs were achieved.
      Compared to neat PHBV, a 149% improvement in tensile strength and 250% increase
      in Young's modulus can be obtained for the resulting nanocomposites with 10 wt.%
      CNCs, more importantly, the T0, T5%, Tmax and Tf increased by 51.4, 36.5, 47.1
      and 52.9 degrees C, respectively. This was due to a combination of CNCs
      reinforcement in the polymeric matrix, and especially the formation of strong
      intermolecular hydrogen bonding interactions through achieving the excellent
      dispersion of CNCs in the PHBV matrix via the solvent exchange procedure, as a
      result, the formation of six-membered ring ester during the degradation process
      of PHBV was clearly suppressed.

PMID- 24750889
TI  - Differential effects of genetically distinct mechanisms of elevating amylose on
      barley starch characteristics.
AB  - The relationships between starch structure and functionality are important in
      underpinning the industrial and nutritional utilisation of starches. In this
      work, the relationships between the biosynthesis, structure, molecular
      organisation and functionality have been examined using a series of defined
      genotypes in barley with low (<20%), standard (20-30%), elevated (30-50%) and
      high (>50%) amylose starches. A range of techniques have been employed to
      determine starch physical features, higher order structure and functionality. The
      two genetic mechanisms for generating high amylose contents (down-regulation of
      branching enzymes and starch synthases, respectively) yielded starches with very
      different amylopectin structures but similar gelatinisation and viscosity
      properties driven by reduced granular order and increased amylose content.
      Principal components analysis (PCA) was used to elucidate the relationships
      between genotypes and starch molecular structure and functionality. Parameters
      associated with granule order (PC1) accounted for a large percentage of the
      variance (57%) and were closely related to amylose content. Parameters associated
      with amylopectin fine structure accounted for 18% of the variance but were less
      closely aligned to functionality parameters. 

PMID- 24750890
TI  - Preparation and characterization of cellulose/hydrous niobium oxide hybrid.
AB  - A composite of cellulose extracted from bagasse with Nb2O5.nH2O in three
      different proportions (16.67, 37.5 and 50.0 wt%) was prepared using the co
      precipitation method. The materials were characterized by X-ray diffractometry
      (XRD), Fourier transform infra-red spectroscopy (FTIR), thermogravimetric
      analysis (TG/DTG), differential scanning calorimetry (DSC) and scanning electron
      microscopy (SEM). TG data obtained show that the presence of inorganic material
      influenced slightly the stability of the hybrid material. The precipitation of
      16.67 wt.% of oxide was sufficient to inhibit the combustion peaks present in the
      DSC curve of cellulose. This work will help find new applications for these
      materials.

PMID- 24750891
TI  - Ulvan and ulvan/chitosan polyelectrolyte nanofibrous membranes as a potential
      substrate material for the cultivation of osteoblasts.
AB  - A new generation of biomaterials composed of the natural polysaccharides, ulvans
      extracted from the green seaweed Ulva rigida and chitosan have been investigated.
      Ulvan, chitosan alone and ulvan/chitosan polyelectrolyte membranes have been
      synthesised and characterised. The structure of the membranes was altered by the
      weight ratio of the polyion components. Fibrous and nanofibrous morphology was
      created, in accordance with a supramolecular self assembly. ATR-FTIR measurements
      suggested the presence of both polycationic chitosan and polyanionic ulvan in the
      polyelectrolyte membranes. The cytocompatibility of these new materials was
      examined by fluorescence microscopy. The results show that ulvan as well as
      ulvan/chitosan membranes promoted the attachment and proliferation of 7F2
      osteoblasts and maintained the cell morphology and viability. Thus, ulvan and
      chitosan which possess unique properties might have high impact in biomedical
      applications as potential scaffold materials.

PMID- 24750892
TI  - O-carboxymethyl chitosan nanoparticles for metformin delivery to pancreatic
      cancer cells.
AB  - In this work we developed metformin loaded O-carboxymethyl chitosan (O-CMC)
      nanoparticles (NPs) by ionic-gelation method. The prepared NPs of 240 +/- 50 nm
      size with spherical morphology exhibited a pH sensitive release of metformin in
      vitro. Cytotoxicity studies showed that the drug-incorporated NPs induced
      significant toxicity on pancreatic cancer cells (MiaPaCa-2) compared to normal
      cells (L929). Metformin loaded NPs exhibited nonspecific internalization by
      normal and pancreatic cancer cells; however metformin released from the NPs
      induced preferential toxicity on pancreatic cancer cells. Our preliminary studies
      suggested that such a novel approach could possibly overcome the current
      limitations of metformin in its clinical application against pancreatic cancer.

PMID- 24750893
TI  - P2X7 receptor inhibition interrupts the progression of seizures in immature rats
      and reduces hippocampal damage.
AB  - AIMS: Early-life seizures, particularly when prolonged, may be harmful to the
      brain. Current pharmacotherapy is often ineffective; therefore, novel neuro-
      and/or glio-transmitter systems should be explored for targeting. The P2X7
      receptor is a cation-permeable channel with trophic and excitability effects on
      neurons and glia which is activated by high amounts of ATP that may be released
      in the setting of injury after severe seizures. Here, we tested the effects of A
      438079, a potent and selective P2X7 receptor antagonist in a lesional model of
      early-life status epilepticus. METHODS: Seizures were induced by intra-amygdala
      kainic acid in 10-day-old rat pups. Electrographic seizure severity, changes to
      P2X7 receptor expression, inflammatory responses and histological effects were
      evaluated. RESULTS: Seizures induced by intra-amygdala kainic acid increased
      levels of P2X7 receptor protein and interleukin-1beta and caused significant cell
      death within the ipsilateral hippocampus. A-438079 rapidly reached the brain
      following systemic injection in P10 rats. Intraperitoneal injection of A-438079
      (5 and 15 mg/kg) 60 min after triggering seizures reduced seizure severity and
      neuronal death within the hippocampus. A-438079 had superior neuroprotective
      effects compared with an equally seizure-suppressive dose of phenobarbital (25
      mg/kg). CONCLUSIONS: These results suggest P2X7 receptor antagonists may be
      suitable as frontline or adjunctive treatments of pediatric status epilepticus or
      other early-life seizures, particularly when associated with brain damage.

PMID- 24750894
TI  - Cardiac remodelling and functional alterations in mild-to-moderate renal
      dysfunction: comparison with healthy subjects.
AB  - INTRODUCTION: Left ventricular (LV) hypertrophy (LVH) and reduced LV function
      correlate with poor prognosis in patients with chronic kidney disease (CKD). Our
      aim is to investigate whether mild-to-moderate CKD is associated with cardiac
      abnormalities. METHODS: Echocardiography, including tissue Doppler imaging, was
      performed in 103 patients with CKD at stages 2-3 and 4-5, and in 53 healthy
      controls. The systolic (s') and diastolic myocardial velocity (e'), and the
      transmitral diastolic flow velocity (E) were measured, and E/e' was calculated.
      RESULTS: Patients with chronic kidney disease had higher mean E/e' than controls
      (mean E/e': controls 5.00 +/- 1.23 versus CKD 4-5 6.36 +/- 1.71, P<0.001 and
      versus CKD 2-3 5.69 +/- 1.47, P = 0.05), indicating altered diastolic function in
      the patients. The CKD groups showed lower longitudinal systolic function than
      controls, as assessed by atrio-ventricular plane displacement and s' (mean s':
      controls 11.5 +/- 1.9 cm s(-1) versus CKD 4-5 10.4 +/- 2.1 cm s(-1) , P = 0.03
      and versus CKD 2-3 10.4 +/- 2.1 cm s(-1) , P = 0.02). The prevalence of LVH was
      higher in patients with CKD than in controls (controls 13% versus CKD 4-5 37%, P
      = 0.006 and versus CKD 2-3 30%, P = 0.03). CONCLUSION: Alterations in systolic
      and diastolic myocardial function can be seen in mild-to-moderate CKD compared
      with controls, indicating that cardiac involvement starts early in CKD, which may
      be a precursor of premature cardiac morbidity.

PMID- 24750895
TI  - Interactions between anaerobic ammonium and sulfur-oxidizing bacteria in a
      laboratory scale model system.
AB  - Fixed nitrogen is released by anaerobic ammonium oxidation (anammox) and/or
      denitrification from (marine) ecosystems. Nitrite, the terminal electron acceptor
      of the anammox process, occurs in nature at very low concentrations and is
      produced via (micro)aerobic oxidation of ammonium or nitrate reduction. The
      coupling of sulfide-dependent denitrification to anammox is particularly
      interesting because besides hydrogen, sulfide is the most important reductant at
      the chemocline of anoxic marine basins and is abundant within sediments. Although
      at MUM concentrations, sulfide may be toxic and inhibiting anammox activity, a
      denitrifying microorganism could convert sulfide and nitrate at sufficiently high
      rates to allow anammox bacteria to stay active despite an influx of sulfide. To
      test this hypothesis, a laboratory scale model system containing a co-culture of
      anammox bacteria and the autotrophic denitrifier Sulfurimonas denitrificans
      DSM1251 was started. Complementary techniques revealed that the
      gammaproteobacterial Sedimenticola sp. took over the intended role of Su.
      denitrificans. A stable coculture of anammox bacteria and Sedimenticola sp.
      consumed sulfide, nitrate, ammonium and CO2 . Anammox bacteria contributed 65-75%
      to the nitrogen loss from the reactor. The cooperation between anammox and
      sulfide-dependent denitrification may play a significant role in environments
      where sulfur cycling is active and where actual sulfide concentrations stay below
      MUM range. 

PMID- 24750896
TI  - Finite element analysis of stress distribution in ceramic crowns fabricated with
      different tooth preparation designs.
AB  - STATEMENT OF PROBLEM: Information about the effect of occlusal preparation
      designs on the stress distribution in different ceramic crowns and the prepared
      tooth is limited. PURPOSE: The purpose of this study was to investigate the
      effects of anatomic and nonanatomic occlusal preparation designs on the stress
      distribution in ceramic crowns, teeth, and bone. MATERIAL AND METHODS: Finite
      element analysis was performed on models of a mandibular second premolar. A load
      of 400 N was applied to the models to test ceramic materials (In-Ceram, Empress
      Esthetic) and occlusal preparation (anatomic, nonanatomic) designs. RESULTS: The
      lowest stress value occurred in the core material in the Empress Esthetic model
      prepared with the nonanatomic occlusal preparation design. In all groups, higher
      stress values were found to be concentrated in the lingual half of the dentin.
      Lower stress values were located near the apex of the pulp tissue and bony tissue
      that surround the root apex. CONCLUSIONS: Differences in preparation designs did
      not result in differences in the distribution or amount of stress in pulp,
      dentin, or bone. The use of different ceramic materials resulted in no
      differences in the amount or distribution of stress in pulp and bone. The use of
      a crown with a high elastic modulus led to increases in stress values in the
      restoration and the dentin margin, and decreases in stress values in the occlusal
      surface of the dentin. The nonanatomic design can be recommended as a favorable
      preparation design for Empress Esthetic ceramic.

PMID- 24750897
TI  - Influenza-associated Hospitalizations and Deaths, Costa Rica, 2009-2012.
AB  - Data needed to guide influenza vaccine policies are lacking in tropical
      countries. We multiplied the number of severe acute respiratory infections by the
      proportion testing positive for influenza. There were ~6,699 influenza
      hospitalizations and 803 deaths in Costa Rica during 2009-2012, supporting
      continuation of a national influenza vaccine program. 

PMID- 24750898
TI  - Seasonality of immune-mediated hemolytic anemia in dogs from southern California.
AB  - OBJECTIVE: To determine if there is seasonal variation in the incidence of canine
      idiopathic immune-mediated hemolytic anemia (IMHA) at 2 specialty hospitals in
      southern California. DESIGN: Retrospective study. To determine seasonality, cases
      of idiopathic IMHA presenting between June 2006 and June 2012 were identified by
      searching medical record databases of 2 large specialty hospitals. The presence
      of anemia with autoagglutination, spherocytosis or a positive Coomb's test and no
      identifiable underlying cause were required for inclusion. Dogs with a history of
      recent travel (within 1 year) were excluded. One hundred and twenty-six dogs, 57
      from a practice in San Diego, and 69 from a practice in Los Angeles, met the
      criteria. RESULTS: The pattern of seasonality differed with practice location (P
      = 0.02). More cases of idiopathic IMHA presented during spring and summer (n =
      39) than winter and fall (n = 18) for the San Diego practice (P = 0.008) but not
      the Los Angeles practice (n = 32 and 37, respectively, P = 0.63). CONCLUSIONS:
      The incidence of idiopathic IMHA in dogs presenting to specialty hospitals
      located in 2 different climates of southern California was different, suggesting
      environmental triggers may be involved. Larger, prospective studies are needed to
      determine whether environmental parameters or undetected infectious disease
      account for some cases of idiopathic IMHA in dogs.

PMID- 24750899
TI  - Relationship between peri-operative outcomes and hospital surgical volume of
      total hip arthroplasty in Japan.
AB  - BACKGROUND: This study aimed to evaluate the relationship between peri-operative
      complication of total hip arthroplasty (THA) and hospital surgical volume.
      METHODS: We reviewed discharge administrative data from 8321 patients who
      underwent primary THA between July and December 2008. Relationships between
      complications and surgical volume were analyzed with multivariate logistic
      regression models including age, sex, and Charlson comorbidity index. Hospitals
      were categorized into four groups according to the 6-month volume of THA
      procedures. RESULTS: The most frequent complication was dislocation (1.41%). Next
      was infection (1.24%). Fracture and pulmonary embolism occurred in less than 1%
      of procedures. Patients who underwent THA in hospitals with the highest surgical
      volume had lower risk of dislocation and infection than those treated in the
      hospitals with the lowest surgical volume (odds ratio [OR] 0.321, 95% confidence
      interval [CI] 0.167-0.572 and OR 0.123, 95% CI 0.020-0.421). Patients aged 65
      years and older were associated with increased risk of dislocation (OR 2.342, CI
      1.555-3.624) and fracture (OR 2.799, CI 1.372-6.301). Females demonstrated lower
      risk of dislocation (OR 0.558, CI 0.352-0.869) and infection (OR 0.560, CI 0.365
      0.882). CONCLUSION: These results indicated that the increase in the risk of peri
      operative dislocation of primary THA may be associated with low hospital surgical
      volume as well as age and male sex.

PMID- 24750900
TI  - Findings of chronic sinusitis on brain computed tomography are not associated
      with acute headaches.
AB  - BACKGROUND: Headache is a common complaint in emergency department (ED) patients.
      Nearly 15% of ED headache patients will have brain computed tomography (CT) done.
      One frequent finding on these scans is "chronic sinusitis." Assuming that
      "chronic sinusitis" is the cause of the patient's headache is a potential source
      of mis-diagnosis. STUDY OBJECTIVE: We hypothesized that CT findings of chronic
      sinusitis occur with equal frequency in patients with atraumatic headache as in
      control patients with minor head injury. METHODS: This is a retrospective, single
      center medical record review of consecutive discharged patients who received
      noncontrast head CT scans in an urban ED for either minor closed head injury or
      atraumatic headache. Each patient's head CT radiologic report was reviewed for
      findings of sinusitis and classified as chronic sinusitis, indeterminate for
      sinusitis, air-fluid levels, or no findings of sinusitis. RESULTS: We enrolled
      500 patients (234 in the atraumatic headache group, 266 in the minor head injury
      group). The two groups were similar except that more women were enrolled in the
      atraumatic headache group. CT findings of chronic sinusitis in the atraumatic
      headache group (22.2%) and the minor head injury group (17.7%; difference 4.5%;
      95% confidence interval of -2.5-11.6%). CONCLUSION: Prevalence of CT findings of
      sinusitis in ED patients with atraumatic headaches and mild head injury are
      similar. This strongly suggests that CT findings of chronic sinusitis in patients
      with atraumatic headache may be incidental, and are rarely the cause of a
      patient's acute headache.

PMID- 24750901
TI  - Streptococcus mitis strains causing severe clinical disease in cancer patients.
AB  - The genetically diverse viridans group streptococci (VGS) are increasingly
      recognized as the cause of a variety of human diseases. We used a recently
      developed multilocus sequence analysis scheme to define the species of 118 unique
      VGS strains causing bacteremia in patients with cancer; Streptococcus mitis (68
      patients) and S. oralis (22 patients) were the most frequently identified
      strains. Compared with patients infected with non-S. mitis strains, patients
      infected with S. mitis strains were more likely to have moderate or severe
      clinical disease (e.g., VGS shock syndrome). Combined with the sequence data,
      whole-genome analyses showed that S. mitis strains may more precisely be
      considered as >2 species. Furthermore, we found that multiple S. mitis strains
      induced disease in neutropenic mice in a dose-dependent fashion. Our data define
      the prominent clinical effect of the group of organisms currently classified as
      S. mitis and lay the groundwork for increased understanding of this understudied
      pathogen. 

PMID- 24750903
TI  - Robotic management of genitourinary injuries from obstetric and gynaecological
      operations: a multi-institutional report of outcomes.
AB  - OBJECTIVE: To evaluate the utility of robotic repair of injuries to the ureter or
      bladder from obstetrical and gynaecological (OBGYN) surgery PATIENTS AND METHODS:
      A retrospective review of all patients from four different high-volume
      institutions between 2002 and 2013 that had a robot-assisted (RA) repair by a
      urologist after an OBGYN genitourinary injury. RESULTS: Of the 43 OBGYN
      operations, 34 were hysterectomies: 10 open, 10 RA, nine vaginally, and five pure
      laparoscopic. Nine patients had alternative OBGYN operations: three caesarean
      sections, three oophorectomies (one open, two laparoscopic), one RA colpopexy,
      one open pelvic cervical cerclage with mesh and one RA removal of an invasive
      endometrioma. In all, 49 genitourinary (GU) injuries were sustained: ureteric
      ligation (26), ureterovaginal fistula (10), ureterocutaneous fistula (one),
      vesicovaginal fistula (VVF; 10) and cystotomy alone (two). In all, 10 patients
      (23.3%) underwent immediate urological repair at the time of their OBGYN RA
      surgery. The mean (range) time between OBGYN injury and definitive delayed repair
      was 23.5 (1-297) months. Four patients had undergone prior failed repair: two
      open VVF repairs and two balloon ureteric dilatations with stent placement. In
      all, 22 ureteric re-implants (11 with ipsilateral psoas hitch) and 15 uretero
      ureterostomies were performed. Stents were placed in all ureteric cases for a
      mean (range) of 32 (1-63) days. In all, 10 VVF repairs and two primary cystotomy
      closures were performed. Drains were placed in 28 cases (57.1%) for a mean
      (range) of 4.1 (1-26) days. No case required open conversion. Two patients (4.1%)
      developed ureteric obstruction after RA repair requiring dilatation and stenting.
      The mean (range) follow-up of the entire cohort was 16.6 (1-63) months.
      CONCLUSIONS: RA repair of GU injuries during OBGYN surgery is associated with
      good outcomes, appears safe and feasible, and can be used successfully
      immediately after injury recognition or as a salvage procedure after prior
      attempted repair. RA techniques may improve convalescence in a patient population
      where quick recovery is paramount.

PMID- 24750902
TI  - A high-content imaging assay for the quantification of the Burkholderia
      pseudomallei induced multinucleated giant cell (MNGC) phenotype in murine
      macrophages.
AB  - BACKGROUND: Burkholderia pseudomallei (Bp), a Gram-negative, motile, facultative
      intracellular bacterium is the causative agent of melioidosis in humans and
      animals. The Bp genome encodes a repertoire of virulence factors, including the
      cluster 3 type III secretion system (T3SS-3), the cluster 1 type VI secretion
      system (T6SS-1), and the intracellular motility protein BimA, that enable the
      pathogen to invade both phagocytic and non-phagocytic cells. A unique hallmark of
      Bp infection both in vitro and in vivo is its ability to induce cell-to-cell
      fusion of macrophages to form multinucleated giant cells (MNGCs), which to date
      are semi-quantitatively reported following visual inspection. RESULTS: In this
      study we report the development of an automated high-content image acquisition
      and analysis assay to quantitate the Bp induced MNGC phenotype. Validation of the
      assay was performed using T6SS-1 (?hcp1) and T3SS-3 (?bsaZ) mutants of Bp that
      have been previously reported to exhibit defects in their ability to induce
      MNGCs. Finally, screening of a focused small molecule library identified several
      Histone Deacetylase (HDAC) inhibitors that inhibited Bp-induced MNGC formation of
      macrophages. CONCLUSIONS: We have successfully developed an automated HCI assay
      to quantitate MNGCs induced by Bp in macrophages. This assay was then used to
      characterize the phenotype of the Bp mutants for their ability to induce MNGC
      formation and identify small molecules that interfere with this process.
      Successful application of chemical genetics and functional reverse genetics siRNA
      approaches in the MNGC assay will help gain a better understanding of the
      molecular targets and cellular mechanisms responsible for the MNGC phenotype
      induced by Bp, by other bacteria such as Mycobacterium tuberculosis, or by
      exogenously added cytokines.

PMID- 24750905
TI  - A note on an alternative DSC approach to study hydration of hyaluronan.

PMID- 24750904
TI  - Update on the Preventive Antibiotics in Stroke Study (PASS): a randomised
      controlled phase 3 clinical trial.
AB  - BACKGROUND: Stroke is a leading cause of death worldwide. Infections after stroke
      occur in 30% of stroke patients and are strongly associated with unfavourable
      outcome. Preventive antibiotic therapy lowers infection rate in patients after
      stroke, however, the effect of preventive antibiotic treatment on functional
      outcome after stroke has not yet been investigated.The Preventive Antibiotics in
      Stroke Study (PASS) is an ongoing, multicentre, prospective, randomised, open
      label, blinded end point trial of preventive antibiotic therapy in acute stroke.
      Patients are randomly assigned to either ceftriaxone at a dose of 2 g, given
      every 24 hours intravenously for four-days, in addition to stroke-unit care, or
      standard stroke-unit care without preventive antibiotic therapy. Aim of the study
      is to assess whether preventive antibiotic treatment improves functional outcome
      at three months by preventing infections. RESULTS: To date, 2,470 patients have
      been included in PASS. Median stroke severity of the first 2,133 patients (second
      interim analysis) is 5 (IQR 3 to 9) on the National Institutes of Health Stroke
      Scale (NIHSS). Due to the PROBE design, no outcome data are available yet. In the
      initial trial protocol we proposed a dichotomisation of the mRS as primary
      analysis of outcome and ordinal regression analysis as secondary analysis of
      primary outcome, requiring a sample size of 3,200 patients. However, ordinal
      analysis of outcome data is becoming increasingly more common in acute stroke
      trials, as it increases statistical power. For PASS, funding is insufficient for
      inclusion of 3,200 patients with the overall inclusion rate of 15 patients per
      week. Therefore we change the analysis of our primary outcome from
      dichotomisation to ordinal regression analysis on the mRS. Power analysis showed
      that with similar assumptions 2,550 patients are needed using ordinal regression
      analysis. We expect to complete follow-up in June 2014. A full statistical
      analysis plan will be submitted for publication before treatment allocation will
      be unblinded. CONCLUSION: The data from PASS will establish whether preventive
      antibiotic therapy in acute stroke improves functional outcome by preventing
      infection. In this update, we changed our primary outcome analysis from
      dichotomisation to ordinal regression analysis. TRIAL REGISTRATION: Current
      controlled trials; ISRCTN66140176. Date of registration: 6 April 2010.

PMID- 24750906
TI  - Effects of pulsed electric field treatments on some properties of tapioca starch.
AB  - Tapioca starch-water dispersions (8.0%, w/w) were subject to pulsed electric
      fields (PEF) at 30, 40 and 50 kV cm(-1), respectively. The effect of the intense
      energy input (Q) of PEF treatment (over 28.85 J g(-1)) on the functionality of
      tapioca starch was investigated. Scanning electron microscopy analysis revealed
      the dissociation and damage of PEF treated tapioca starch granules. X-ray
      diffraction analysis demonstrated that tapioca starch tended to transform from
      crystalline to amorphous structure after PEF treatments. It was found that higher
      energy input (>49.36 J g(-1)) could destroy the crystal region of tapioca starch.
      Meanwhile, with increasing electric field strengths, the gelatinization
      temperature, the gelatinization enthalpy, the peak viscosity and the breakdown
      viscosity of PEF-treated samples showed a remarkable decrease. These results
      suggest that PEF treatments would be a promising physical method to modify the
      properties of starch in order to obtain desired products in food industry.

PMID- 24750907
TI  - Rheological properties of concentrated solutions of galactomannans in an ionic
      liquid.
AB  - The rheological behavior of galactomannans in concentrated solutions was examined
      by using dynamic viscoelasticity measurements. Concentrated solutions of three
      galactomannans, guar gum, tara gum, and locust bean gum were prepared with an
      ionic liquid 1-butyl-3-methylimidazolium chloride as the solvent. Each
      galactomannan solution showed angular frequency dependence curves of the storage
      modulus and the loss modulus which were characteristic of a solution of entangled
      polymer chains. The molecular weight between entanglements (Me) was obtained from
      the plateau modulus and the concentration dependence of Me showed Me in the
      molten state (Me,melt) to be 4.6*10(3), 3.2*10(3), and 2.7*10(3) for guar gum,
      tara gum, and locust bean gum, respectively. It was found that the material
      constant Me,melt depends on the mannose/galactose ratio of the galactomannans.
      The number of monosaccharide units between entanglements in the molten state for
      the galactomannans varied within the range found for other polysaccharides such
      as cellulose and agarose in ionic liquids, suggesting that all the galactomannans
      take a random-coil conformation in ionic liquid solutions. 

PMID- 24750908
TI  - Composition and cytotoxicity of a novel polysaccharide from brown alga (Laminaria
      japonica).
AB  - A novel polysaccharide WPS-2-1, with an average molecular weight of 80 kDa, was
      purified from aqueous extracts of Laminaria japonica. Monosaccharides analysis
      revealed that WPS-2-1 was composed of mannose, rhamnose and fucose with a molar
      ratio of 1.0:2.3:1.2. Analysis by periodate oxidation-Smith degradation indicated
      that WPS-2-1 had a backbone of array by (1->4)-glycosidic linkages. Cytotoxicity
      assay showed that WPS-2-1 presented significantly higher antitumor activities
      against A375 and BGC823 cells with a dose-dependent manner, and exhibited lower
      cytotoxicity to vascular smooth muscle cells. The results suggested that WPS-2-1
      should be explored as a potential antitumor agent with low toxicity.

PMID- 24750909
TI  - Preparation of conductive paper composites based on natural cellulosic fibers for
      packaging applications.
AB  - Conducting paper based on natural cellulosic fibers and conductive polymers was
      prepared using unbleached bagasse and/or rice straw fibers (as cellulosic raw
      materials) and polyaniline (PANi) as conducting polymer. These composites were
      synthesized by in situ emulsion polymerization using ammonium persulfate (APS) as
      oxidant in the presence of dodecylbenzene sulfonic acid (DBSA) as emulsifier. The
      prepared composites were characterized using Fourier transform infrared (FTIR),
      thermal gravimetric analysis (TGA), differential scanning calorimeter (DSC), and
      their morphology was investigated using scanning electron microscope (SEM).
      Electrical conductivity measurements showed that the conductivity of the paper
      sheets increases by increasing the ratio of PANi in the composite. Mechanical
      properties of the paper sheets were also investigated, the results revealed that
      the values of breaking length, burst factor, and tear factor are decreased with
      increasing ratio of added PANi, and this effect is more pronounced in bagasse
      based composites. The new conductive composites can have potential use as anti
      static packaging material or anti-bacterial paper for packaging applications. 

PMID- 24750910
TI  - Bacterial cellulose produced by a new acid-resistant strain of Gluconacetobacter
      genus.
AB  - A bacterial strain isolated from the fermentation of Colombian homemade vinegar,
      Gluconacetobacter medellensis, was investigated as a new source of bacterial
      cellulose (BC). The BC produced from substrate media consisting of various carbon
      sources at different pH and incubation times was quantified. Hestrin-Schramm (HS)
      medium modified with glucose led to the highest BC yields followed by sucrose and
      fructose. Interestingly, the microorganisms are highly tolerant to low pH: an
      optimum yield of 4.5 g/L was achieved at pH 3.5, which is generally too low for
      other bacterial species to function. The cellulose microfibrils produced by the
      new strain were characterized by scanning and transmission electron microscopy,
      infrared spectroscopy X-ray diffraction and elemental analysis. The
      morphological, structural and chemical characteristics of the cellulose produced
      are similar to those expected for BC.

PMID- 24750912
TI  - Preparation, characterization and technological evaluation of CMC derived from
      rice-straw as thickening agents in discharge, discharge-resist and burn-out
      printing.
AB  - Carboxymethyl cellulose samples of different D.S. values were prepared from rice
      straw via pulping followed by etherification with monochloroacetic acid under the
      catalytic action of sodium hydroxide. The prepared derivatives were assessed for
      D.S., rheological properties as well as suitability as thickening agents in
      different printing styles. It was found that carboxymethyl cellulose derived from
      rice straw is characterized by a non-Newtonian pseudoplastic behavior and its
      apparent viscosity at any specific rate of shear depends on the D.S. All the
      prepared derivatives could be used successfully as thickening agents in discharge
      and/or discharge/resist printing of cotton fabrics. Furthermore, they could be
      used also as thickening agent for burn-out printing style of wool/polyester
      blended fabrics using sodium hydroxide. Attractive samples could be obtained via
      using these techniques. 

PMID- 24750911
TI  - Toward an alternative compatibilizer for PLA/cellulose composites: grafting of
      xyloglucan with PLA.
AB  - Poly(L-lactic acid) (PLLA) chains were grafted on xyloglucan substrates via ring
      opening polymerization of the L-lactide monomer. Different parameters such as the
      nature of the substrate (native or modified xyloglucan) and the substrate/monomer
      ratios were varied in the synthesis to achieve different lengths of the grafted
      chains. A range of experimental techniques including infrared spectroscopy and
      nuclear magnetic resonance were used to characterize the final product. Thermal
      analysis showed that the glass transition temperature of xyloglucan was decreased
      from 252  degrees C to 216  degrees C following the grafting of PLLA. The
      grafting of less hydrophilic chains from xyloglucan also affected the interaction
      with water: the PLLA-grafted xyloglucan was insoluble in water and the moisture
      uptake could be decreased by about 30%. Xyloglucan adsorbs strongly to cellulose;
      therefore such a graft copolymer may improve the compatibility between cellulose
      fibers and PLLA. The PLLA-grafted xyloglucan may be useful as a novel
      compatibilizer in fiber-reinforced PLLA composites.

PMID- 24750913
TI  - Additivity of water sorption, alpha-relaxations and crystallization inhibition in
      lactose-maltodextrin systems.
AB  - Water sorption of lactose-maltodextrin (MD) systems, structural relaxations and
      lactose crystallization were studied. Accurate water sorption data for non
      crystalline lactose previously not available over a wide range of water activity,
      aw (<0.76aw) were derived from lactose-MD systems data. Structural relaxations
      and crystallization of lactose in lactose-maltodextrin (MD) systems were strongly
      affected by water and MD. At high MD contents, inhibition of crystallization was
      significant. Inhibition with a high dextrose equivalent (DE) MD was more
      pronounced possibly because of molecular number and size effects. At 0.55-0.76aw,
      inhibition increased with increasing MD content. At aw>0.66, the rate of lactose
      crystallization decreased at increasing MD contents. Different MDs with similar
      Tg in lactose-MD systems showed different crystallization inhibition effects. The
      results of the present study showed that the DE in selection of MD for
      applications has important effects on component crystallization characteristics.

PMID- 24750914
TI  - Synthesis of antibacterial film CTS/PVP/TiO2/Ag for drinking water system.
AB  - A CTS/PVP/TiO2/Ag functional film was prepared as an antibacterial composite used
      in storing drinking water. The orthogonal experiment showed that the optimal
      conditions for preparing membranes with best antibacterial activity and tensile
      strength are c(AgNO3)=0.08%, c(TiO2)=0.20%, c(CTS)=2.25%, and c(PVP)=3.00%. The
      FT-IR spectrum implies that hydrogen bands are formed between acetyl in PVP and
      hydroxyl in CTS molecule, and -NH and -OH of CTS have some interactions with
      sliver nano-particles (nano-Ags) which were reduced in situ. The SEM images show
      that the TiO2 particles are displayed on the surface and embedded in the film.
      And nano-Ags are further proved through XRD and SEM images. The DSC curves show
      that the film has a favorable compatibility and heat stability. In application
      study, it is proved that this film has sustainable antibacterial activity and is
      safe in use.

PMID- 24750915
TI  - Apoptosis-induced anti-tumor effect of Curcuma kwangsiensis polysaccharides
      against human nasopharyngeal carcinoma cells.
AB  - This study aimed to investigate the effect of Curcuma kwangsiensis
      polysaccharides on the viability of human nasopharyngeal carcinoma cell line CNE
      2 cells, and explore the possible mechanisms. CNE-2 cells were treated with
      various concentrations of C. kwangsiensis polysaccharides, then the
      proliferation, apoptosis and the protein expression of apoptosis-related
      regulators p53 and Bcl-2 were assessed. The results demonstrated that C.
      kwangsiensis polysaccharides can significantly inhibit the proliferation of CNE-2
      cells, which was possibly through the induction of apoptosis mediated by
      attenuating Bcl-2 expression and promoting p53 expression. The present study
      therefore indicates that C. kwangsiensis polysaccharides could be developed into
      potential drugs for nasopharyngeal carcinoma treatment. 

PMID- 24750916
TI  - Complexation of WPI and microwave-assisted extracted agars with different
      physicochemical properties.
AB  - The complex formation between whey protein isolate (WPI) and agar has been
      investigated and their interactions were monitored as a function of the
      physicochemical properties of agar, the pH and the ionic strength of the medium.
      Agars from Gracilaria vermiculophylla were extracted under different MAE
      conditions and characterized according to their physicochemical properties. By
      using microwave irradiation a wide variety of agars was obtained, as different
      MAE conditions results in polyelectrolytes with distinct properties. UV-vis (in
      optical dispersion (O.D.) model) spectroscopy and isothermal titration
      calorimetry (ITC) have been used to study the formation of insoluble (coacervate)
      complexes. MAE agars revealed excellent properties for complex formation with
      WPI. The binding of WPI to MAE agar samples has been shown to be the result of
      different contributions. O.D. and ITC results showed that the molecular mass and
      the sulfate content of different agars had a determinant effect on coacervate
      formation. 

PMID- 24750917
TI  - Sulfation pattern of citrus pectin and its carboxy-reduced derivatives: influence
      on anticoagulant and antithrombotic effects.
AB  - Citrus pectin (CP), a polysaccharide composed of [->4)-alpha-D-GalpA-(1->]n, was
      submitted to one or four carboxy-reduction cycles, resulting in CP-CR1 and CP
      CR4, which had 40% and 2% of GalpA units, respectively. The polysaccharides were
      chemically sulfated and their anticoagulant and antithrombotic effects
      determined. Sulfated polysaccharides (CP-S, CP-CR1S and CP-CR4S) had different
      anticoagulant activities, doubling APTT at concentrations of 28.7, 13.2, and 4.9
      MUg/ml respectively. CP-CR1S and CP-CR4S also showed antithrombotic activity in
      vivo with ED50 of 3.01 and 1.70 mg/kg, respectively. Like heparin, they inhibited
      thrombin by a mechanism dependent on AT and HCII. Their hemorrhagic potential was
      also similar to that of heparin. According to methylation analysis, 91.1% and
      50.2% of 6-O-position in CP-CR4S and CP-CR1S were sulfated, respectively.
      Therefore, substitution of carboxyl groups by sulfate esters in these
      polysaccharides increases the anticoagulant and antithrombotic effects.

PMID- 24750918
TI  - Water-soluble N-[(2-hydroxy-3-trimethylammonium)propyl]chitosan chloride as a
      nucleic acids vector for cell transfection.
AB  - To endow the cationic polysaccharides with solubility in the whole pH-range
      without loss of functionality of the amino groups, different chitosan samples
      were treated with glycidyltrimethylammonium chloride. Each modified unit of the
      exhaustively alkylated quaternized chitosan (QCht) contained both quaternary and
      secondary amino groups. The intercalated dye displacement assay and zeta
      potential measurements implied stability of QCht polyplexes at physiological
      conditions and protonation of the secondary amino groups in slightly acidic media
      which is favorable for transfection according to proton sponge mechanism. The
      cytotoxicity and transfection efficacy increased with the chain lengthening.
      Nevertheless, the longest chains of QCht, 250 kDa were less toxic than PEI for
      COS-1 cells and revealed comparable and even significantly higher transfection
      activity of siRNA and plasmid DNA, respectively. Thus, highly polymerized QCht
      (250 kDa) provided the highest level of the plasmid DNA transfection being 5 and
      80 times more active than QCht (100 kDa) and QCht (50 kDa), respectively, and 4
      fold more effective than PEI, 25 kDa. The established influence of QCht molecular
      weight on toxicity and transfection efficacy allows elaborating polysaccharide
      vectors that possess rational balance of these characteristics.

PMID- 24750919
TI  - Inclusion complex of methyl-beta-cyclodextrin and olanzapine as potential drug
      delivery system for schizophrenia.
AB  - Olanzapine (OLP), the most important atypical antipsychotic drug of the new
      generation, a high cost drug, has low aqueous solubility, affecting its
      dissolution and absorption. Its complexation with modified cyclodextrins (CDs) is
      designed to achieve novel vectorization systems with higher solubility,
      consequently higher bioavailability. From the CD selection, among beta-CD, methyl
      beta-CD (MbetaCD) and hydroxypropyl-beta-CD, it was obtained a phase solubility
      diagram suggesting a 1:1 (mol:mol) OLP-CD stoichiometry and complexation
      constants of 966.9, 149.4 and 91.1 L/mol, respectively. The MbetaCD was selected
      for the inclusion complexes (IC) attainment, a physical mixture (PM) and a
      rotatory evaporator product (ROE). The analysis showed differences in the
      structure, morphology and performance of OLP, MbetaCD, PM and ROE, revealing the
      occurrence of interactions between drug and CD. The ROE presented the higher
      dissolution efficiency and stability. The results suggest that the IC was
      formation, being a technological resource efficient and profitable for drug
      delivery.

PMID- 24750921
TI  - Physicochemical characterization of biosurfactant and its potential to remove oil
      from soil and cotton cloth.
AB  - An alkaliphilic bacterium, Klebsiella sp. strain RJ-03, produced a biosurfactant,
      which showed low viscosity with pseudoplastic rheological behavior and exhibited
      emulsification activity with oils and hydrocarbons. The biosurfactant has
      excellent oil removing efficiency as compared to chemical surfactants. The
      isolated biosurfactant has compatibility with detergents and enhanced oil
      removing efficiency from soil and cotton cloths. It comprised of sugar, uronic
      acid, protein and sulfate. GC-MS analysis confirmed the presence of six
      monosaccharides (w/w), glucose (6.65%), galactose (23.98%), rhamnose (14.94%),
      mannose (17.54%), fucose (9.47%) and 6-O-Me-galactose (1.4%). It is a high
      molecular weight, thermostable biopolymer showing degradation above 300  degrees
      C. Positive ion reflector mode of MALDI TOF-TOF MS analysis revealed series of
      low and mid range mass peaks (m/z) corresponding to mono-, di-, tri- and oligo
      saccharides content. The NMR, FT-IR, EDX-SEM, AFM and PSD analysis confirmed the
      presence of functional groups, bonds, elements and particle size respectively.

PMID- 24750920
TI  - Novel vaccine adjuvant LPS-Hydrogel for truncated basic fibroblast growth factor
      to induce antitumor immunity.
AB  - The need to enhance the immunogenicity of tumor-associated antigens and modulate
      the resulting immune responses has prompted the development of new adjuvants. We
      prepared a novel adjuvant, lipopolysaccharides (LPS) loaded thermosensitive
      hydrogel (LPS-Hydrogel), for truncated basic fibroblast growth factor (tbFGF)
      peptide to enhance immunological responses and improve therapeutic effects in
      cancer. When co-formulated with tbFGF, LPS-Hydrogel formed antigen-adjuvant
      complexes, which enhanced antibody and cell-mediated responses in mice, thus
      promoting a more balanced antibody-mediated and cytotoxic T lymphocyte (CTL)
      mediated immune response to inhibit tumor growth and metastases in vivo.
      Furthermore, the secretion of IFN-gamma and IL-4 was detected, confirming
      activation of the two immune responses in vivo. There were no significant
      systemic toxicities observed with tbFGF-LPS-Hydrogel treatment. These results
      suggested that the thermosensitive and biodegradable LPS-Hydrogel was a novel
      adjuvant and carrier for peptide vaccines in cancer immunotherapy. 

PMID- 24750922
TI  - Immuno-enhancing activity of sulfated Auricularia auricula polysaccharides.
AB  - The crude total Auricularia auricula polysaccharide (AAPct) was extracted by
      water decoction and ethanol precipitation, protein was removed to obtain total A.
      auricula polysaccharide (AAPt), then was graded into AAP1 and AAP2 through column
      chromatography. sAAPt, sAAP1 and sAAP2 were prepared by chlorosulfonic acid
      pyridine method. In vitro test, the effects of sAAPt, sAAP1, sAAP2, AAPt, AAP1
      and AAP2, on chicken peripheral lymphocytes proliferation were compared. The
      results showed that sAAPt and sAAP1 demonstrated better effect. In vivo test, 14
      day-old chickens were injected respectively with sAAPt, sAAP1, AAPt and AAP1 at
      the first vaccination of ND vaccine, once a day for three days. On days 7, 14, 21
      and 28 after the first vaccination, the peripheral lymphocytes proliferation and
      antibody titer were determined. The results indicated that sAAPt possessed the
      best efficacy and would be expected to be used as a component of a new-type
      immunopotentiator. 

PMID- 24750923
TI  - A novel injectable chitosan/polyglutamate polyelectrolyte complex hydrogel with
      hydroxyapatite for soft-tissue augmentation.
AB  - This study demonstrated a chitosan (CS)/polyglutamate (PG) polyelectrolyte
      complex (PEC) hydrogel combined with spherical hydroxyapatite (HAp) particles as
      an injectable dermal filler for soft-tissue augmentation. The CS/PG PEC hydrogel
      with oppositely charged ionic cross-linking, a high gel content, and low
      degradation rate was introduced as a carrier to achieve high shape and volume
      stability. An MTT assay indicated that the CS/PG PEC had satisfactory cell
      biocompatibility. This PEC/HAp hydrogel showed good structural integrity in a PBS
      solution for up to 60 days. Clinical manageability was indexed by an injection
      force measurement through sterile 27-gauge needles using a texture analyzer. In
      an animal study, 0.2 mL of the PEC and PEC/hydroxyapatite (HAp) were implanted
      within the dorsal dermis of a swine ear. Injected tissue areas were biopsied 2
      weeks, and 2 and 6 months after the injection. According to the histomorphometric
      results, the PEC and PEC/HAp groups showed percentages of retention of the
      maximum height of the cross-section of about 44% and 73% at 6 months. New
      collagen was observed in the central position indicating a possible collagenesis
      effect. These results suggest that this PEC/HAp system can be used as an
      alternative for soft-tissue augmentation.

PMID- 24750924
TI  - Extraction of polysaccharides from herbal Scutellaria barbata D. Don (Ban-Zhi
      Lian) and their antioxidant activity.
AB  - The response surface methodology was employed to study the extraction of
      polysaccharides from Scutellaria barbata D. Don. The quantitative effects of
      extraction temperature, time, number and ratio of water to raw material on yield
      of polysaccharides were investigated with Box-Behnken design. The experimental
      data were fitted to a second-order polynomial equation using multiple regression
      analysis and also analyzed using the appropriate statistical methods. By solving
      the regression equation and analyzing 3D plots, the optimum condition was at
      extraction temperature 70  degrees C, time 3h, numbers 3 and ratio of water to
      raw material 18.5 mL/g. Under these conditions, the experimental polysaccharides
      yield was 2.43+/-0.11%, which was in good agreement with the predicted value. The
      antioxidant activities of the polysaccharides were evaluated in vitro. A
      potential antioxidant activity of S. barbata polysaccharides provides a
      scientific basis for the use of this herb in traditional medicine as an
      antioxidant.

PMID- 24750925
TI  - Effect of sectioning and water on resin-embedded sections of corn starch granules
      to analyze inner structure.
AB  - Resin-embedded sections and paired block surface of corn starch granules were
      observed using atomic force microscopy (AFM) and scanning electron microscopy to
      analyze the fine inner structure of starch granules and observe artifacts.
      Wrinkles were formed on the starch surfaces because of shear stress caused by the
      knife. Sectioned starches were isotropically expanded by water, and the growth
      rings and cracks between the growth rings were observed only on the sections.
      From this result, it was considered that the growth rings clearly showed
      shrinkage and/or corrosion of both edges of the ring during drying of the
      sections. Moreover, many small particles (width, ~30 nm; height, several
      nanometers) were clearly observed on the growth rings. These particles could be
      single clusters (~10 nm) of amylopectin molecules, considering the effect of the
      AFM tip radius.

PMID- 24750926
TI  - Antioxidant capacity and light-aging study of HPMC films functionalized with
      natural plant extract.
AB  - The aims of this work were to functionalize edible hydroxypropyl methylcellulose
      (HPMC) films with natural coloring biomolecules having antioxidant capacity and
      to study their photo-aging stability in the films. HPMC films containing a
      natural red color compound (NRC) at the level of 1, 2, 3 or 4% (v/v) were
      prepared by a casting method. A slight degradation of films color was observed
      after 20 days of continuous light exposure. The antioxidant activity of NRC
      incorporated films was stable during different steps of film formation and 20
      days of dark storage. On the other hand, antioxidant activity of samples stored
      under light was significantly affected after 20 days. FTIR (Fourier Transformed
      Infrared) spectroscopy was used to characterize the new phenolic polymeric
      structures and to study the photo-degradation of films. The results showed a good
      polymerization phenomenon between NRC and HPMC in polymer matrix giving a natural
      color to the films. NRC showed an ability to protect pure HPMC films against
      photo-degradation. This phenomenon was directly proportional to the concentration
      of NRC. 

PMID- 24750927
TI  - Synthesis, characterization and antimicrobial activity of dextran stabilized
      silver nanoparticles in aqueous medium.
AB  - A simple one-step rapid synthetic route is described for the preparation of
      silver nanoparticles by reduction of silver nitrate (AgNO3) using aqueous dextran
      solution which acts as both reducing and capping agent. The formation of silver
      nanoparticles is assured by characterization with UV-vis spectroscopy, atomic
      force microscopy (AFM), transmission electron microscopy (TEM) and X-ray
      diffraction (XRD). The absorbance of the silver nanoparticles is observed at 423
      nm. The AFM image clearly shows the surface morphology of the well-dispersed
      silver nanoparticles with size range of 10-60 nm. TEM images show that the
      nanoparticles are spherical in shape with ~5-10 nm dimensions. The crystallinity
      of Ag nanoparticles is assured by XRD analysis. The antimicrobial activity of as
      synthesized silver nanoparticles is tested against the bacteria, Bacillus
      subtilis, Bacillus cereus, Escherichia coli, Staphylococcus aureus and
      Pseudomonas aeruginosa. The bacterial growth is inhibited by gradual reduction of
      the concentration of the silver nanoparticles.

PMID- 24750928
TI  - Study on the stability of beta-carotene microencapsulated with pinhao (Araucaria
      angustifolia seeds) starch.
AB  - Native and hydrolyzed pinhao starches were used as coating materials for beta
      carotene microencapsulation by freeze-drying. The purpose of the present study
      was to evaluate the stability of beta-carotene encapsulated under three different
      conditions: in the presence of ultraviolet light at 25+/-2  degrees C, in the
      dark at 25+/-2  degrees C and in the dark at 10.0+/-0.2  degrees C. The color of
      the samples was also analyzed. Microcapsules prepared with native starch showed
      the lowest stability during storage. In contrast, microcapsules encapsulated with
      12 dextrose equivalent (DE) hydrolyzed starch exhibited the highest stability.
      First-order kinetic and Weibull models were applied to describe the degradation
      of beta-carotene over time. The R(2) values of the Weibull model were greater
      than those of the first-order kinetic model. Moreover, multivariate analyses
      (principal component and cluster analyses) were also conducted.

PMID- 24750929
TI  - New improved method for fructooligosaccharides production by Aureobasidium
      pullulans.
AB  - Fructooligosaccharides are prebiotics with numerous health benefits within which
      the improvement of gut microbiota balance can be highlighted, playing a key role
      in individual health. In this study, an integrated one-stage method for FOS
      production via sucrose fermentation by Aureobasidium pullulans was developed and
      optimized using experimental design tools. Optimization of temperature and
      agitation speed for maximizing the FOS production was performed using response
      surface methodology. Temperature was found to be the most significant parameter.
      The optimum fermentation conditions were found to be 32  degrees C and 385 rpm.
      Under these conditions, the model predicted a total FOS production yield of 64.7
      gFOS/gsucrose. The model was validated at optimal conditions in order to check
      its adequacy and accuracy and an experimental yield of 64.1 (+/-0.0)
      gFOS/gsucrose was obtained. A significant improvement of the total FOS production
      yields by A. pullulans using a one-stage process was obtained.

PMID- 24750930
TI  - Effects of ripening stage and cultivar on physicochemical properties and pectin
      nanostructures of jujubes.
AB  - Two Chinese jujube (Zizyphus jujuba) cultivars ('Huanghua' and 'Zhanhua') at
      unripe and ripe stages were investigated. During ripening, the weight, pH,
      hardness, and chewiness of both cultivars decreased while titratable acidity,
      total soluble solid content, and pectin contents increased. More than 75% pectins
      of the fruits were water-soluble pectin (WSP). Pectins shared the common major
      compositions of Gal, Rha and GalUA. For both cultivars, most of the chain widths
      were between 47 and 70 nm for unripe while less than 40 nm for ripe jujubes.
      Compared to unripe fruits, all pectins of ripe fruits had less percentage of wide
      and long pectin chains. All the pectin contents of cultivar 'Huanghua' changed to
      a degree greater than that of cultivar 'Zhanhua' during ripening. Changes of
      pectin nanostructure and neutral sugar composition might be responsible for the
      major physicochemical properties of jujubes.

PMID- 24750931
TI  - Nanoreinforced bacterial cellulose-montmorillonite composites for biomedical
      applications.
AB  - Polymer composites containing solid clay nanoparticles have attracted immense
      attention due to the reinforced physico-mechanical properties of the final
      product. Bacterial cellulose-montmorillonite (BC-MMT) composites were prepared by
      impregnation of BC sheets with MMT suspension. FE-SEM showed that MMT adsorbed
      onto the surface as well as penetrated into the matrix of the BC sheets. Peaks
      for both BC and MMT were present in the FT-IR spectrum of the composite. XRD also
      showed diffraction peaks for MMT and BC with a slight decrease in the composite
      crystallinity from 63.22% of pure BC to 49.68% of BC-MMT3. The mechanical and
      thermal properties of BC-MMT composites were significantly improved compared to
      those of the pure BC. Tensile strength for composites was increased up to 210 MPa
      from 151.3 Mpa (BC) while their degradation temperature extended from 232 
      degrees C (BC) up to 310  degrees C. Similarly, the water holding capacity was
      decreased while the water release rate was improved for the BC-MMT composites as
      compared to the pure BC.

PMID- 24750932
TI  - Mechanical properties of calcium alginate fibers produced with a microfluidic
      device.
AB  - Fibers are important microstructural elements in many foods. The main objective
      of this research was to produce calcium alginate fibers with uniform diameters
      (about 300 and 550 MUm) using a microfluidic device (MFD) and to study the effect
      of concentration of sodium alginate [Alg] and calcium chloride [CaCl2] on their
      mechanical properties (MP). Moisture content (MO) and MP as maximum tensile
      stress (sigmamax), tensile strain at break (DeltaL/L0) and apparent Young's
      modulus (E) of fibers were determined and a statistical model and surface
      responses were developed as a function of [Alg] and [CaCl2]. As [CaCl2] increased
      first a strengthening and then a weakening of fibers were observed. Furthermore,
      sigmamax increased with the addition of Ca(2+) and a maximum of sigmamax was
      obtained for a [CaCl2] around 1.4% (exceeding several times the stoichiometric
      requirements of the carboxylate groups of the polymer). Such behavior prompted a
      molecular explanation of what happens during gelation based on the "egg-box
      model" and this model is tried to complete. Moreover, fibers with [Alg] >=1.8%
      showed high extensibility (DeltaL/L0 around 100%) and low values of MO. High
      values of E (~0.5 MPa) were obtained for [CaCl2] close to 1.4%. A greater
      understanding is needed of the interaction between cation-polysaccharide-water,
      taking into account [Alg] and [CaCl2] to predict the mechanical behavior of
      fibers. Calcium alginate fibers are important in food engineering as texture and
      microencapsulation agents.

PMID- 24750933
TI  - Novel thermo- and pH-responsive hydroxypropyl cellulose- and poly (L-glutamic
      acid)-based microgels for oral insulin controlled release.
AB  - Novel smart microgel particles made of poly (L-glutamic acid-2-hydroxylethyl
      methacrylate) (PGH) and hydroxypropyl cellulose-acrylic acid (HPC-AA) have been
      successfully prepared via emulsion polymerization. The dynamic light scattering
      measurement reveals that the average hydrodynamic radius <Rh> and hydrodynamic
      radius distributions f (Rh) of the microgel particles depend on the temperature
      and pH value thus the microgel particles exhibit both pH- and temperature
      sensitivity. In vitro release study shows that the amount of insulin released
      from microgels in the gastric juice (at pH 1.2) is significantly less than that
      in the intestinal fluid (at pH 6.8). These results indicate that the resultant
      microgels are of potential for use in intelligent oral drug delivery systems.

PMID- 24750934
TI  - Ionic liquids as solvents for dissolution of corn starch and homogeneous
      synthesis of fatty-acid starch esters without catalysts.
AB  - Ionic liquids (ILs) utilized for dispersing cellulose have gained increasing
      attention in recent years, but the number of the reports using ILs for starch is
      still limited. In this study, 1-butyl-3-methylimidazolium chloride ([BMIM]Cl) and
      1-ethyl-3-methlyimidazolium acetate ([EMIM]AC) were used to dispersing corn
      starch. Dimethyl sulfoxide (DMSO), a traditional organic solvent for starch, was
      added into [BMIM]Cl, and the mixture of [BMIM]Cl/DMSO was utilized for dispersing
      corn starch as well. Results showed that the starch granules dispersed in ILs was
      much smaller than native starch granules, and large starch aggregates were
      partially formed. Starch granules dispersed in [BMIM]Cl at 100  degrees C for 60
      min remained less crystallinity than native starch granules, while it was
      disappeared when starch granules were dispersed in [EMIM]AC at 100  degrees C for
      60 min. Homogenous synthesis of fatty-acid starch esters without catalysts in
      these ILs was also studied. The degree of substitution (DS) value of starch
      laurate was reached to 0.053, 0.068 and 0.100 in [BMIM]Cl, [EMIM]AC and the
      mixture of [BMIM]Cl/DMSO, respectively, at the reaction conditions of lauric
      acid/AGU molar ratio 1:5, temperature 120  degrees C at a reaction time of 3 h.

PMID- 24750935
TI  - Combined QCMD and AFM studies of lysozyme and poly-L-lysine-poly-galacturonic
      acid multilayers.
AB  - A quartz crystal microbalance with dissipation monitoring (QCMD) has been used to
      monitor the adsorption and structure of lysozyme monolayers and multilayers, and
      poly-L-lysine (PLL)-polygalacturonic acid (PGalA) multilayers at a solid-liquid
      interface using freshly-cleaved mica as a substrate. QCMD measurements were
      complemented with atomic force microscopy (AFM). AFM images revealed that
      lysozyme formed incomplete monolayers and provided a basis for calculation of the
      thickness of the protein film. Comparative studies of adsorption onto standard
      and mica-coated quartz crystals showed higher areal mass adsorption and a longer
      time adsorption process for mica-coated quartz crystals. Simultaneous AFM images
      and QCMD data were obtained for lysozyme, linear PLL-PGalA and 7 nm PLL dendrimer
      PGalA multilayers. The layer-by-layer deposited multilayer films exhibited
      viscoelastic properties and their growth followed a non-linear regime, associated
      with the PLL diffusion in and out of the film formation for linear PLL-PGalA
      films. For the PLL 7 nm dendrimer-PGalA films the AFM images revealed marked
      changes in surface roughness during layer by layer deposition: these changes
      influence the interpretation of the QCMD data and provide additional information
      on the growth and structure of the multilayers.

PMID- 24750936
TI  - Purification of a polysaccharide from Gynostemma pentaphyllum Makino and its
      therapeutic advantages for psoriasis.
AB  - In current study, a water-soluble polysaccharide (GP-I), with a molecular mass of
      33 kDa, was purified from Gynostemma pentaphyllum. Gas chromatography (GC)
      analysis suggested that it was composed of Glc, Gal, Man, Rha and Ara with a
      ratio of 5.3: 4.2: 3.0: 0.7: 0.8. The GP-I (25, 50, 100, 200 and 400 MUg/ml) was
      found to have significant anti-proliferative effects on HaCat cells in a dose
      dependent manner, as measured by MTT assay. On the contrary, Trypan blue
      exclusion experiment indicated that GP-I had no cytotoxicity to HaCat cells.
      Moreover, the decrease of mitochondrial membrane potential (MMP) in GP-I treated
      cells was also observed, indicating apoptosis in HaCat cells. Besides, tumor
      necrosis factor-alpha (TNF-alpha), a vital pro-inflammatory cytokine in
      psoriasis, in the supernatant of HaCat cells was dramatically reduced by GP-I.
      Collectively, these findings suggested that GP-I was a promising agent to be
      developed for psoriasis treatment in clinical therapy.

PMID- 24750937
TI  - Effects of barley and oat beta-glucan structures on their rheological and thermal
      characteristics.
AB  - In order to understand the relationship between chemical structure and physical
      properties of cereal beta-glucans, the beta-glucans with identical Mw (98.4-99.2
      kDa) and Rg (21.1-22.0 nm) were isolated from chal and gwangan barley, and ohl
      oat, and their linkage structure, flow behavior, and thermal properties were
      investigated. Previously, we established a purification method of 3-O-cellobiosyl
      glucose (DP3) and 3-O-cellotriosyl-glucose (DP4) (Yoo, Lee, Chang, Lee, & Yoo,
      2007) and applied these authentic standards to quantify the ratio of beta
      (1,4)/(1,3) linkages in cereal beta-glucans. beta-Glucans isolated from two
      barley cultivars had greater proportion of DP3 than did the oat, and within
      barley cultivars chal barley beta-glucan had significantly larger amount of DP3
      over gwangan cultivar. Thus, chal barley beta-glucan had the greatest molar ratio
      (2.53) of DP3 to DP4, and ohl oat had the lowest (1.51). While all the beta
      glucan solutions showed strong shear thinning behavior, ohl oat beta-glucan with
      higher proportion of DP4 exhibited the highest viscosity among the beta-glucan
      samples. After 3 freeze-thaw cycles of 3% (w/v) beta-glucan samples, chal barley
      beta-glucan had lower onset (To) and peak (Tp) temperatures (28.3 and 36.7 
      degrees C, respectively) than those of gwangan barley (33.6 and 39.9  degrees C)
      and ohl oat (37.9 and 46.9  degrees C) did, and the heat scan profiles were
      thermoreversible. The To and Tp of inter-chain associations decreased as the
      DP3:DP4 ratio of the beta-glucan increased. From this study, it was suggested
      that cellotetraosyl units and longer beta-(1,4)-linked segments would be a major
      contributor for improving solution viscosity and gel formation of cereal beta
      glucans.

PMID- 24750938
TI  - Laccase mediated conjugation of heat treated beta-lactoglobulin and sugar beet
      pectin.
AB  - Laccase, an oxidative enzyme, was used to catalyze the hetero and homo covalent
      conjugation between ferulic acid in sugar beet pectin (SBP) and tyrosine in
      heated beta-lactoglobulin (H_BLG). The conjugation of SBP and H_BLG was confirmed
      by peak position using size exclusion chromatography, multi angle laser light
      scattering, refractive index, and UV detection. H_BLG, pre-treated with laccase,
      eluted at an earlier volume with greater UV280 absorbance than non-laccase
      treated dispersions. Tyrosine decreased in H_BLG that contained laccase treated
      SBP samples. Heat enhanced exposure of tyrosine in BLG and improved conjugation
      with SBP by laccase. H_BLG.SBP conjugates with laccase had improved solubility
      than laccase untreated dispersions at pH values near the isoelectric point of
      BLG. 

PMID- 24750939
TI  - Properties of a novel type of starch found in the double mutant "sweet wheat".
AB  - The double mutant "sweet wheat" (SW), which produces substantial amounts of
      sugars in immature seeds, is missing two starch synthases, namely granule-bound
      starch synthase I (GBSSI) and starch synthase IIa (SSIIa). The lack of these two
      enzymes causes major changes in the attributes of SW seed, starch, and starch
      granules. SW seeds appear normal during early stages of development, but become
      shrunken when seeds begin to mature and dry. However, even in immature seed,
      starch granules are small and misshapen, and high levels of maltose are present
      throughout seed development. The crystallinity of SW starch is altered in that a
      major peak typical of the cereal A-type diffraction pattern is absent, and the
      gelatinization temperature of SW starch is considerably lower than that of wild
      type starch. Amylopectin from SW seed has a substantially lower molecular weight
      than that from wild-type seed, and a low molecular weight peak with a bimodal
      distribution is found only in SW starch. This peak contains linear malto
      oligosaccharides as well as short, branched glucans. SW starch has an increased
      proportion of branches with DP<10, and chains with DP 2 and 3 are particularly
      increased. These changes suggest that sweet wheat starch is being modified in an
      atypical manner by isoamylases and/or beta-amylases. 

PMID- 24750940
TI  - Synthesis of new glycosaminoglycans-like families by regioselective oxidation
      followed by sulphation of glucoglucuronan from Rhizobium sp. T1.
AB  - Glycosaminoglycan-like polysaccharides were prepared from Rhizobium sp. T1
      polysaccharide using the TEMPO (nitroxyl radical 2,2,6,6-tetramethylpiperidine-1
      oxyl radical) mediated oxidation. The structure of this new polyglucuronic acid
      sodium salt was analyzed by (13)C NMR spectra and HPAEC-PAD chromatography.
      Therefore, new polysaccharide containing only glucuronic acid monomers in both
      beta-(1,3) and beta-(1,4) linkage was obtained by the complete TEMPO-mediated
      oxidation of C6 primary hydroxyl groups of glucose of glucoglucuronan from
      Rhizobium sp. T1. Sulphation of this beta-(1,3),beta-(1,4)-polyglucuronic acid
      sodium salt was carried out using SO3/DMF reagent. These results suggested a new
      synthetic route using both TEMPO-mediated oxidation and sulphation of
      polysaccharides from Rhizobium sp. in developing glycosaminoglycans mimic to
      enhance the profitability of its low-cost production and processing industries.
      This novel carbohydrate derivative might find use as cheaper surrogates of
      glycosaminoglycans in the cosmetics and pharmaceutical fields.

PMID- 24750941
TI  - Bioactivity of the crude polysaccharides from fermented soybean curd residue by
      Flammulina velutipes.
AB  - The solid-state fermentation, reusing soybean curd residue (SCR) as a solid
      substrate, was conducted for producing polysaccharides by Flammulina velutipes
      (F. velutipes). The optimal fermentation conditions were 74.5% of moisture
      content, 9.69 of inoculum size and 30.27 of C/N ratio by response surface
      methodology. 59.15 mg/g of polysaccharides were obtained. F. velutipes
      polysaccharides were subsequently extracted from fermented SCR by ultrasonic
      assisted extraction. The optimal extract conditions were 30 min, 80  degrees C,
      150 W and 20 of water to solid ratio and 106.74 mg/g of polysaccharides were
      obtained. Furthermore, the antioxidant and the immunomodulatory activities of
      polysaccharides were assessed. The results showed that polysaccharides exhibited
      a strong DPPH radical scavenging activity, SOD-like activity, stimulatory the
      proliferation of the macrophage, the production of nitric oxide, phagocytosis and
      the protection on Doxorubicin damage. These could lay the foundation for changing
      SCR into a nutritious functional food or a food additive.

PMID- 24750942
TI  - Chitosan/cashew gum nanogels for essential oil encapsulation.
AB  - Nanogels based on chitosan and cashew gum were prepared and loaded with Lippia
      sidoides oil. Several parameters such as cashew gum concentration and relative
      oil content in the matrix had their influence on nanogel properties investigated.
      Nanogels were characterized regarding their morphologies, particle size
      distributions, zeta potential, Fourier transform infrared spectroscopy and
      essential oil contents. The release profile was investigated by UV/vis
      spectroscopy and its efficacy was determined through bioassays. Results showed
      that samples designed using relative ratios matrix:oil 10:2, gum:chitosan 1:1 and
      5% gum concentration showed high loading (11.8%) and encapsulation efficiency
      (70%). Nanogels were found to exhibit average sizes in the range 335-558 nm. In
      vitro release profiles showed that nanoparticles presented slower and sustained
      release. Bioassays showed that larval mortality was related mainly to oil
      loading, with samples presenting more effective larvicide efficacies than the
      pure L. sidoides oil.

PMID- 24750943
TI  - Improved production of chitin from shrimp waste by fermentation with epiphytic
      lactic acid bacteria.
AB  - The epiphytic Lactobacillus acidophilus SW01 isolated from shrimp waste (SW) was
      used in SW fermentation. During the fermentation the lag phase of SW01 was hardly
      observed. The pH of the fermentation broth decreased to 3.86 within 12h and
      reached the lowest point at 3.73 after 48 h. This indicates a quick and deep
      acidification process by SW01. Besides, SW01 was observed to have high protease
      activity. As a result, the minerals and protein in SW were quickly removed with
      their contents decreasing to 0.73% and 7.8% respectively after 48 h fermentation.
      In the pilot scale fermentation, the pH was 3.99 and 3.86 respectively after 12
      and 24 h fermentation. The mineral and protein contents were 0.98% and 8.44%
      respectively after 48 h fermentation. The residue of the fermented SW contains
      less than 1% minerals and can be easily transformed into chitin by a mere
      bleaching treatment.

PMID- 24750945
TI  - Mechanism of cellulose gelation from aqueous alkali-urea solution.
AB  - Molecular process of regeneration-gelation of cellulose from aqueous alkali-urea
      solvent was monitored by synchrotron-radiation X-ray. The wide-angle diffraction
      from cellulose during regeneration, both by coagulant and heating, gave
      information on behavior of cellulose molecules, i.e. the glucopyranoside rings
      first stack by hydrophobic interaction to form monomolecular sheets, which then
      line up by hydrogen bonding to form Na-cellulose IV type crystallites (hydrate
      form of cellulose II). While such a process in regeneration of cellulose has been
      hypothesized and supported by molecular dynamics or monitoring of mercerization
      process, our observation finally confirmed it experimentally. This knowledge will
      be useful in understanding behavior of cellulose molecules during regeneration,
      leading to better controls of resulting structure and properties.

PMID- 24750944
TI  - N,N,N-Trimethyl chitosan nanoparticles for controlled intranasal delivery of HBV
      surface antigen.
AB  - Hepatitis B virus surface antigen (HBsAg) loaded N,N,N-trimethyl chitosan
      nanoparticles (N-TMC NPs) were formulated and studied for controlled intranasal
      delivery. The size and surface properties of the NPs can be tuned by modifying
      the concentration of N-TMC and found to be 66+/-13, 76+/-9 nm for 0.25 and 0.5
      wt.% respectively. Loading of 380 and 760 MUl of HBsAg yielded 143+/-33, 259+/-47
      nm sized spherical N-TMC NPs with highest loading efficiency and capacity of 90
      93%, and 96-97% respectively. In vitro drug release analysis ensured 93%
      cumulative release of HBsAg antigen over prolonged period (43 days). In vivo
      immunological study was performed using 6-8 weeks old female BALB mice and
      reveals adjuvants efficiency of NPs for antigen is highly stable and better than
      standard. Obtained results show that N-TMC NPs can be extensively used in
      controlled intra nasal delivery to treat various diseases including hepatitis B
      and allergic rhinitis.

PMID- 24750946
TI  - Methacrylic acid-triggered phase transition behavior of thermosensitive
      hydroxypropylcellulose.
AB  - Methacrylic acid (MAA)-triggered phase transition of thermosensitive
      hydroxypropyl cellulose (HPC) was studied. The phase transition temperature of
      0.1 wt.% HPC aqueous solutions was dramatically reduced from 41  degrees C to 8 
      degrees C as the MAA concentration increased from 0 wt.% to 4 wt.%. The sharp
      decrease of HPC phase transition temperature triggered by MAA may be attributed
      to strong hydrogen bonding between MAA and HPC. It may be proposed that the
      hydrogen bonding of MAA with HPC restricts the interaction of water with HPC and
      so reduces the solubility of HPC in water and improves the hydrophobic
      association of HPC. Furthermore, MAA attaching on HPC polymer chains was
      polymerized to form surfactant-free PMAA nanogels around ambient temperature when
      HPC collapsed forming PMAA nanogels. Effect of MAA concentration and
      polymerization temperature on the size and size distribution of PMAA nanogels was
      investigated.

PMID- 24750947
TI  - Influence of skin blood flow and source-detector distance on near-infrared
      spectroscopy-determined cerebral oxygenation in humans.
AB  - Most near-infrared spectroscopy (NIRS) apparatus fails to isolate cerebral
      oxygenation from an extracranial contribution although they use different source
      detector distances. Nevertheless, the effect of different source-detector
      distances and change in extracranial blood flow on the NIRS signal has not been
      identified in humans. This study evaluated the extracranial contribution, as
      indicated by forehead skin blood flow (SkBF) to changes in the NIRS-determined
      cerebral oxyhaemoglobin concentration (O2 Hb) by use of a custom-made
      multidistance probe. Seven males (age 21 +/- 1 year) were in a semi-recumbent
      position, while extracranial blood flow was restricted by application of four
      different pressures (+20 to +80 mmHg) to the left temporal artery. The O2 Hb was
      measured at the forehead via a multidistance probe (source-detector distance; 15,
      22.5 and 30 mm), and SkBF was determined by laser Doppler. Heart rate and blood
      pressure were unaffected by application of pressure to the temporal artery, while
      SkBF gradually decreased (P<0.001), indicating that extracranial blood flow was
      manipulated without haemodynamic changes. Also, O2 Hb gradually decreased with
      increasing applied pressure (P<0.05), and the decrease was related to that in
      SkBF (r = 0.737, P<0.01) independent of the NIRS source to detector distance.
      These findings suggest that the NIRS-determined cerebral oxyhaemoglobin is
      affected by change in extracranial blood flow independent of the source-detector
      distance from 15 to 30 mm. Therefore, new algorithms need to be developed for
      unbiased NIRS detection of cerebral oxygenation. 

PMID- 24750948
TI  - (15)N- and (2)H proteomic stable isotope probing links nitrogen flow to archaeal
      heterotrophic activity.
AB  - Understanding how individual species contribute to nutrient transformations in a
      microbial community is critical to prediction of overall ecosystem function. We
      conducted microcosm experiments in which floating acid mine drainage (AMD)
      microbial biofilms were submerged - recapitulating the final stage in a natural
      biofilm life cycle. Biofilms were amended with either (15)NH4(+) or deuterium
      oxide ((2)H2O) and proteomic stable isotope probing (SIP) was used to track the
      extent to which different members of the community used these molecules in
      protein synthesis across anaerobic iron-reducing, aerobic iron-reducing and
      aerobic iron-oxidizing environments. Sulfobacillus spp. synthesized (15)N
      enriched protein almost exclusively under iron-reducing conditions whereas the
      Leptospirillum spp. synthesized (15)N-enriched protein in all conditions. There
      were relatively few (15)N-enriched archaeal proteins, and all showed low atom%
      enrichment, consistent with Archaea synthesizing protein using the predominantly
      (14)N biomass derived from recycled biomolecules. In parallel experiments using
      (2)H2O, extensive archaeal protein synthesis was detected in all conditions. In
      contrast, the bacterial species showed little protein synthesis using (2)H2O. The
      nearly exclusive ability of Archaea to synthesize proteins using (2)H2O may be
      due to archaeal heterotrophy, whereby Archaea offset deleterious effects of (2)H
      by accessing (1)H generated by respiration of organic compounds.

PMID- 24750949
TI  - [The alpha-1 antitrypsin deficiency: advances in knowledge and unsolved
      questions].

PMID- 24750950
TI  - [Regeneration of airway epithelium].
AB  - INTRODUCTION: Epithelial regeneration is a complex process. It can lead to the
      remodeling of the airway epithelium as in asthma, COPD or cystic fibrosis.
      BACKGROUND: The development of in vivo and in vitro models has allowed the
      analysis of remodeling mechanisms and showed the role of components of
      extracellular matrix, proteases, cytokines and growth factors. Airway epithelial
      progenitors and stems cells have been studied in these models. However, their
      identification remains difficult. CONCLUSION: Identification and characterization
      of airway epithelial progenitor/stem-cells, and a better knowledge of the
      regeneration process may allow the development of new therapeutic strategies for
      airway epithelial reconstitution.

PMID- 24750951
TI  - [Proposal for a systematic analysis of polygraphy or polysomnography for
      identifying and scoring abnormal events occurring during non-invasive
      ventilation].
AB  - Non-invasive ventilation (NIV) is recognised as an effective treatment for
      chronic hypercapnic respiratory failure. Monitoring NIV during sleep may be
      preferable to daytime assessment. This paper reports the findings of an
      international consensus group, which systematically analysed nocturnal
      polygraphic or polysomnographic tracings recorded with either volume-cycled or
      pressure-cycled ventilators. A systematic description of nocturnal respiratory
      events, which occur during NIV, is proposed: leaks, obstruction at different
      levels of the upper airway (glottis and/or pharynx), with or without decrease of
      respiratory drive and asynchrony. 

PMID- 24750952
TI  - [Pulmonary resection using video-assisted thoracoscopic surgery--20 years
      experience].
AB  - Major lung resection using minimally invasive techniques - video-assisted
      thoracoscopic surgery (VATS) - was first described 20 years ago. However, its
      development has been slow in many countries because the value of this approach
      has been questioned. Different techniques and definitions of VATS are used and
      this can be confusing for physicians and surgeons. The benefit of minimally
      invasive thoracic surgery was not always apparent, while many surgeons pointed to
      suboptimal operative outcomes. Recently, technological advances (radiology, full
      HD monitor and new stapler devices) have improved VATS outcomes. The objectives
      of this review are to emphasize the accepted definition of VATS resection,
      outline the different techniques developed and their results including morbidity
      and mortality compared to conventional approaches. Minimally invasive thoracic
      surgery has not been proven to give superior survival (level one evidence)
      compared to thoracotomy. A slight advantage has been demonstrated for short-term
      outcomes. VATS is not a surgical revolution but rather an evolution of surgery.
      It should be considered together with the new medical environment including
      stereotactic radiotherapy and radiofrequency. VATS seems to be more accurate in
      the treatment of small lung lesions diagnosed with screening CT scan. In the
      academic field, VATS allows easier teaching and diffusion of techniques.

PMID- 24750953
TI  - [Inhaled treatments in cystic fibrosis: what's new in 2013?].
AB  - In the past few years some new inhaled drugs and inhalation devices have been
      proposed for the treatment of cystic fibrosis. Breath-controlled nebulizers allow
      increased pulmonary deposition, with a lower variability and a shorter delivery
      time. The new dry powder formulations of tobramycin, colistine and mannitol
      require a change in the inhalation technique which must be slow and deep. In the
      field of the inhaled mucolytic drugs, hypertonic saline and mannitol have an
      indication in some patients. With regard to antibiotics, dry-powder tobramycin
      and colistine can be substituted for the same drug delivered by nebulization.
      Nebulized aztreonam needs more studies to determine its place. These new
      treatments represent a definite advance for cystic fibrosis patients and need to
      be known by all practitioners. Their position in our therapeutic arsenal remains
      to be accurately defined. 

PMID- 24750954
TI  - [One more word about the diagnostic. A metapsychological approach].
AB  - Nearly a decade since the first experiment in France of the so-called
      "announcement policy" a concerted effort, the pooling of skills of health
      professionals from different backgrounds, have had noticeable positive effects on
      the daily practice. This article attempts at analyzing the question that was
      causing the application of former patients and their main complaint: the lack of
      communication and its direct consequences, anguish and loneliness. Subsequently,
      the announcement policy, this multifaceted approach, had consisted of creating
      for the patient what can be called "a good enough environment able to hold". It
      is therefore not a plan but a disposal (if we are willing to agree on the fact
      that these are the qualities of the therapeutic setting that count and not the
      format by itself). Considering the ipseity of each patient, the uniqueness of
      each particular situation, of each social background, the need for harmonization
      of the announcement policy is questionable. Harmonization does not mean
      uniformity. The quality of this policy must be adapted closer to each case.
      However, it must be based on the basic principles and might also take into
      account the dimension of anguish. These fundamental principles are directly
      derived from the principles of medical humanism, those that have brought meaning
      to scientific progress. 

PMID- 24750955
TI  - [Hepatic involvement in hereditary alpha-1-antitrypsin deficiency].
AB  - Apha-1-antitrypsin deficiency is an autosomal recessive genetic disorder seen in
      all races. The molecular defect is a specific mutation of the SERPINA1 gene
      leading to synthesis of an abnormal protein (alpha-1-antitrypsin Z) that cannot
      be secreted and polymerizes in the endoplasmic reticulum of hepatocytes. The
      inter-individual variability in the responses to intracellular stress induced by
      the accumulation of abnormal polymers and the mechanisms allowing their
      degradation is, without doubt, responsible for the different clinical
      manifestations of the disease. The disease affects the liver where the abnormal
      protein is synthesized and the lung, which is its place of action. Liver
      involvement is well recognized in homozygous infants of the phenotype ZZ. In this
      situation the disease may present a varying picture from neonatal cholestasis
      (about 15% of neonatal defects) to cirrhosis. However, evolution towards
      cirrhosis affects less than 3% of infants with the ZZ phenotype and it is
      preceded in 80% of cases by neonatal cholestasis. In adolescents or adults the
      manifestations associated with alpha-1-antitrypsin deficiency are usually limited
      to biochemical abnormalities but may lead to cirrhosis or hepatocellular
      carcinoma. The hepatic disorder and its complications are treated symptomatically
      though the pulmonary involvement may benefit from substitution treatment. More
      specific treatments targeting the molecular and cellular abnormalities are the
      subject of research. 

PMID- 24750956
TI  - [The epidemiology of pollen allergy].
AB  - The prevalence of seasonal allergic rhinitis can be established through surveys
      performed in a sample of the general population. These surveys are based on a
      questionnaire, which could lead to an overestimate of prevalence rates, and on
      measurements of specific IgE, which need to be interpreted in the light of the
      responses to the questionnaire. Such surveys are few in France and need to be
      updated. Risk factors for seasonal allergic rhinitis are genetic, epigenetic and
      environmental. Relationships between exposure to pollen and health can be
      documented through ecological and panel surveys. Panel surveys may give
      information on threshold levels and dose-response relationships. In addition to
      pollen exposure, global warming and air pollutants act as cofactors. Monitoring
      of both pollen exposure and its health effects should be encouraged and
      strengthened. 

PMID- 24750957
TI  - [Cardiovascular morbidity associated with obstructive sleep apnea syndrome].
AB  - INTRODUCTION: The obstructive sleep apnoea syndrome (OSAS) had become a major
      public health concern in modern society due to its high prevalence but, above
      all, to its associated morbidity, especially cardiovascular. BACKGROUND:
      Untreated OSAS is associated with an increased incidence of fatal (myocardial
      infarction and stroke) (odds ratio: 2.87) and non-fatal cardiovascular events
      (myocardial infarction, stroke, coronary artery bypass surgery and coronary
      angiography) (odds ratio: 3.17). Moreover, the prevalence of hypertension in
      patients with OSAS is high, between 35 and 80%. The pathophysiological mechanisms
      leading to these complications are mainly due to intermittent hypoxia secondary
      to repeated episodes of apnoea/hypopnoea during sleep. These mechanisms include
      sympathetic hyperactivation, impairment of vasomotor reactivity, vascular
      inflammation, oxidative stress and metabolic disorders. In patients with OSAS,
      the impact of continuous positive pressure is proven in terms of prevention of
      cardiovascular events although blood pressure reduction is limited. Obviously
      these effects are proportional to observance. CONCLUSION: OSAS does increase the
      cardiovascular risk, independently of other risk factors. Although the impact of
      treatment is relatively low in decreasing blood pressure, it seems essentially
      effective in preventing cardiovascular morbidity. Therefore, OSAS screening, and
      the association of specific treatments in cardio-metabolic patients and OSAS
      patients respectively, should be included in clinical strategies.

PMID- 24750958
TI  - Creating an institutional resource for research education and career development:
      a novel model from Oregon Clinical and Translational Research Institute.
AB  - We have created an education and career development program within the CTSA
      structure at OHSU that serves the entire institution. We believe that this is
      unusual in scope among CTSA programs and has contributed to an increase in career
      development funding and research skills among fellows and faculty. While the key
      element is the institutional scope, important elements include: Tailoring
      programs of emphasis to points of inflection on the career pathway. Minimizing
      barriers to education by creating a flexible, tuition-free program. An integrated
      one-stop education and career development approach. An institutional program for
      career development award applicants as well as recipients. This career
      development program was developed within the context of a midsize health science
      university but the overall strategy may be applied to other CTSAs to simplify and
      reduce costs of education program development.

PMID- 24750959
TI  - Extracellular visfatin has nicotinamide phosphoribosyltransferase enzymatic
      activity and is neuroprotective against ischemic injury.
AB  - AIM: Visfatin, a novel adipokine, is predominantly produced by visceral adipose
      tissue and exists in intracellular and extracellular compartments. The
      intracellular form of visfatin is proved to be nicotinamide
      phosphoribosyltransferase (NAMPT) and exhibits neuroprotection through
      maintaining intracellular NAD(+) pool. However, whether extracellular form of
      visfatin has NAMPT activity and the effect of extracellular visfatin in cerebral
      ischemia are unknown. METHODS AND RESULTS: Plasma concentrations of visfatin,
      NAD(+) , and ATP were increased in mice upon cerebral ischemia. Cultured glia,
      but not neuron, was able to secrete visfatin. Oxygen-glucose deprivation (OGD)
      stress increased the secretion of visfatin from glia. Extracellular recombinant
      mouse wild-type visfatin, but not mouse H247A-mutant enzymatic-dead visfatin, had
      NAMPT enzymatic function in vitro. Treatment of wild-type visfatin, but not H247A
      mutant enzymatic-dead visfatin, significantly attenuated detrimental effect of
      OGD on the cell viability and apoptosis in both cultured mouse neuron and glia.
      Treatment of neutralizing antibody, abolished the protective effect of
      extracellular visfatin on cell viability, but failed to block the antiapoptotic
      effect of extracellular visfatin. At last, we observed that plasma visfatin
      concentrations decreased in 6-month-old but not 3-month-old SHR-SP compared with
      that in age-matched Wistar-Kyoto rats. Inhibition of NAMPT enzymatic function of
      visfatin (by FK866) accelerated the occurrence of stroke in SHR-SP. CONCLUSIONS:
      Extracellular visfatin has NAMPT enzymatic activity and maybe be neuroprotective
      just as intracellular visfatin in cerebral ischemic injury.

PMID- 24750960
TI  - Cognitive task performance and symptoms contribute to personality abnormalities
      in first hospitalized schizophrenia.
AB  - Chronic schizophrenia patients have personality abnormalities and cognitive
      deficits that are associated with poor clinical, social, and vocational outcomes.
      Very few studies have examined relationships between personality and cognitive
      function, and chronic illness effects may have confounded those studies. In this
      study personality traits in clinically stable first episode schizophrenia
      patients (21M, 9F) and psychiatrically healthy controls (38M, 24F) were measured
      with the NEO-FFI, a self-report measure of neuroticism, extraversion, openness,
      agreeableness, and conscientiousness. All subjects completed the Information,
      Digit Span, Vocabulary, and Digit Symbol subtests of the Wechsler Adult
      Intelligence Scale; and Trails A and B. Standard statistical techniques were used
      to quantify relationships between personality and symptom levels and/or task
      performance, and relative contributions of diagnosis and task performance to
      personality variance. Patients showed elevated mean neuroticism and openness, and
      reduced mean extraversion, agreeableness and conscientiousness. Task performance
      and negative symptoms contributed significantly and uniquely to most personality
      dimensions in patients. Task performance accounted for significant amounts of
      personality variance even after accounting for diagnosis, and it also contributed
      to personality variance in controls. These results suggest that cognitive
      deficits and negative symptoms contribute to consistently observed personality
      abnormalities in this disorder, and that the contribution of neuropsychological
      performance to personality variance may be independent of diagnostic
      classification. Personality abnormalities in schizophrenia may stem from the
      neurocognitive deficits associated with this disorder, and add to their adverse
      effects on social and vocational functioning. 

PMID- 24750961
TI  - Discovery of novel P-glycoprotein-mediated multidrug resistance inhibitors
      bearing triazole core via click chemistry.
AB  - A novel series of P-glycoprotein (P-gp)-mediated multidrug resistance (MDR)
      inhibitors bearing a triazol-phenethyl-tetrahydroisoquinoline scaffold were
      designed and synthesized via click chemistry. Most of the synthesized compounds
      showed higher reversal activity than verapamil (VRP). Among them, the most potent
      compound 5 showed a comparable activity with the known potent P-gp inhibitor WK-X
      34 with lower cytotoxicity (IC50s > 100 MUm). Compared with VRP, compound 5
      exhibited more potency in increasing drug accumulation in K562/A02 MDR cells.
      Moreover, compound 5 persisted longer chemo-sensitizing effect (>24 h) than VRP
      (<6 h) with reversibility. Given the low intrinsic cytotoxicity and the potent
      reversal activity, compound 5 may represent a promising candidate for developing
      P-gp-mediated MDR inhibitor.

PMID- 24750962
TI  - Mesentery-like steri-strip: a scarless drain fixation.

PMID- 24750963
TI  - Reflections on acromio-clavicular dislocations.
AB  - A number of surgical and nonsurgical techniques have been used in the recent past
      for the treatment of this not uncommon traumatic condition. Thus far, no
      agreement has been reached regarding the method most likely to consistently
      render good results. Uppermost in determining the treatment has been the degree
      of displacement of the clavicle and the prevention of possible cosmetically
      unacceptable complications. Advances in the surgical care of most fractures and
      dislocations have lead to the current belief and practice among the majority of
      orthopaedic surgeons that every effort should be made to correct any deviation
      from the normal produced by the injury. I submit that skilful neglect and
      acceptance of acromio-clavicular dislocation is an option worth considering. When
      the dislocation is accepted, the vast majority of patients do well, functionally
      and aesthetically. Chronic pain is an extremely rare situation; and the resulting
      deformity, from the cosmetic point of view, an uncommon problem. If this is the
      case, what is the problem that reconstructive surgery proposes to address? 

PMID- 24750964
TI  - [What should an orthopaedic surgeon know about biotribology of total hip
      arthroplasty].
AB  - The objective of this paper is to briefly review the engineering biotribology of
      total hip arthroplasty (THA). At present the issue of lubrication, wear and
      friction within a THA is being studied in detail and the results have been
      published in a number of papers. The reason is obvious since the rate at which
      the articulating surfaces wear off affects the longevity of a THA to a great
      extent. Seeking an optimal biotribological configuration remains an important
      task for both the researchers and orthopaedic surgeons. In order to enable the
      orthopaedic community to think over THA biotribology and, at the same time,
      communicate with the representatives of technical professions, knowledge of the
      basic principles of biotribology and their understanding is necessary.

PMID- 24750965
TI  - [Arthroscopic stabilisation of acute acromioclavicular dislocation using the
      TighRope device].
AB  - PURPOSE OF THE STUDY: To present the TightRope (Arthrex, Naples, FL) technique
      and its results in the arthroscopic stabilisation of acute acromioclavicular
      joint (ACJ) dislocation carried out at our department. MATERIAL AND METHODS: From
      July 2009 till December 2010, arthroscopic stabilisation of acute ACJ dislocation
      was performed in 22 patients. The group consisted of 18 men and four women with
      an average age of 37.4 years. The Rockwood type III to type V ACJ dislocations
      (III, 16; IV, 1; V, 5) were indicated for surgery. The average interval between
      injury and surgery was 5.4 days. In all cases, a second-generation TightRope
      implant was inserted by the EndoButton technique joining the distal end of the
      clavicle and the coracoid process. The results were evaluated using the UCLA
      Shoulder Scale at 6 months after surgery. RESULTS: All 22 patients returned to
      their pre-operative activities without any restriction of shoulder motion within
      5 months of surgery. The average post-operative UCLA score was 31.2 points
      (range, 28 to 35). Radiographic evidence of the loss of full reduction, with no
      effect on the clinical outcome, was recorded in four patients (18%) during post
      operative rehabilitation. Of these, one had Rockwood type III, two had type IV
      and one had type V dislocations. One patient suffered post-operative pull-out of
      the implant from the coracoid; three patients showed skin wound healing by second
      intention above the lateral clavicle, with one requiring surgical repair under
      local anaesthesia. There was no neurovascular complication, intra- or
      postoperative fracture of the coracoid process or lateral clavicle, or deep wound
      infection. DISCUSSION: Arthroscopic stabilisation of acute ACJ dislocation is a
      minimally invasive procedure providing the coracoclavicular ligament complex with
      dynamic stability. In comparison with open procedures, it is less painful post
      operatively, allows the patients to return early to daily activities and has a
      better cosmetic effect. It eliminates the necessity of removing the
      osteosynthetic material, as is the case in commonly used techniques such as
      Bosworth's method, K-wiring, osteorrhaphy or hook plate insertion. The loss of
      full reduction in four patients, as observed on radiographs during their
      rehabilitation, was not accompanied by any clinical problems and is in agreement
      with the findings of other authors. In our group, it occurred in Rockwood grade
      IV and grade V dislocations. For these, there is a possibility of using two
      implants in order to increase stability and prevent the loss of full reduction
      but this involves a higher risk of coracoid fracture, extension of operative time
      and higher costs. However, a loss of reduction in some patients has also been
      reported by the authors who have used two implants. Therefore we prefer using a
      single TightRope implant, particularly in acute grade III ACJ dislocations
      requiring surgical treatment in patients engaged in repetitive overhead
      activities related to sports or occupation. CONCLUSIONS: Arthroscopic
      stabilisation of acute ACJ dislocations using a single TightRope implant is an
      elegant minimally invasive method with good results in indicated cases. It proves
      efficient particularly in Rockwood type III injuries in patients who have to do
      repetitive overhead activities. Acute type IV and type V ACJ dislocations treated
      by this technique show a loss of full reduction on radiographs more frequently,
      although no effect on the clinical outcome is evident.

PMID- 24750966
TI  - [Hinged external fixation in orthopaedic and trauma surgery of the elbow].
AB  - PURPOSE OF THE STUDY: A hinged external fixator of the elbow provides stable
      fixation of the joint while maintaining the range of its motion. The aim of the
      study was to evaluate a group of patients in whom an external fixator was used to
      manage severe injuries to the elbow, namely, traumatic unstable dislocation,
      unstable fracture-dislocation, and elbow fractures not permitting management by
      primary osteosynthesis. This also involved assessment of early elbow mobilisation
      and a comparison of this group with a group of patients treated conservatively
      for less severe elbow injuries. MATERIAL AND METHODS: A group of 25 patients were
      evaluated at a follow-up of 18 months. There were 10 women and 15 men; the
      average age was 48 years (range, 20 to 76). The external fixator was applied in
      13 patients, of whom eight had unstable elbow dislocation, three had unstable
      fracture-dislocation and two suffered a comminuted supracondylar fracture of the
      distal humerus. The hinged fixator was removed at an average of 7.6 weeks (range,
      3 to 9 weeks). In the group of 12 patients treated conservatively by plaster cast
      application and subsequent rehabilitation, five had elbow dislocation without
      ligament injury and seven had elbow dislocation with ulnar collateral ligament
      injury. None of them showed any instability. The patients were evaluated on the
      basis of clinical and radiological findings, with the Mayo elbow performance
      (MEP) score being used for clinical assessment. RESULTS: At a follow-up of 18
      months, the patients with the external fixator showed the average range of motion
      at the elbow joint of 127 degrees  (105 degrees  to 140 degrees ), the MEP score
      of 92 points (75 to 100) and restriction of elbow extension by 8 degrees  (0
      degrees  to 40 degrees ). In the conservatively treated patients, the range of
      motion was 133 degrees  (112 degrees  to 145 degrees ), the MEP score was 95
      points (85 to 100) and extension restriction by 8 degrees  (0 degrees  to 22
      degrees ). X-ray examination showed a congruent joint in both groups. The use of
      external fixator was associated with minor complications: transient radial nerve
      irritation in one case, and pin-tract infection in two cases (23%) which healed
      spontaneously after screw removal. DISCUSSION: The optimal management of a
      complex elbow injury should results in restoring joint stability and its full
      range of motion. However, this is often difficult to achieve by surgical means
      and a marked restriction of movement remains a frequent consequence of severe
      elbow injury. CONCLUSIONS: Elbow injuries differ from patient to patient and
      therefore the approach to their treatment has to be individual in every patient.
      A hinged external fixator provides stable fixation and allows for early movement
      of the elbow. Maintenance of the range of motion facilitated by the hinged
      fixator is not at the expense of joint stability or fracture non-union. Based on
      the results presented here, we recommend the use of external fixation in severe
      unstable elbow fractures and in fractures in which primary osteosynthesis cannot
      be used because of soft tissue injury.

PMID- 24750967
TI  - [Recurrent intra-articular bleeding episodes in haemophiliacs. Treatment outcomes
      in the patients at the university hospital motol in 1985-2005].
AB  - PURPOSE OF THE STUDY: Chronic synovitis is a common finding in people with
      haemophilia. It regularly appears after recurrent episodes of intra-articular
      bleeding. The bleeding originates from the subsynovial venous plexus underlying
      the capsule where a lack of thromboplastic activity has been demonstrated.
      Therefore, the changed synovium appears to be a treatment target. There are
      several methods which can be used to remove the synovial layer from the joint.
      The aim of our study was to asses the efficacy of different treatment approaches
      used in a group of haemophiliacs between 1985 and 2005 in our hospital. MATERIAL
      AND METHODS: A group of 30 patients with bleeding disorders was evaluated in the
      study. There were 29 men with haemophilia and one woman with von Wilebrandt
      factor deficiency. Their age ranged from 6 to 18 (median 13) years. They
      underwent a total of 68 interventions including surgical synovectomy (n=28),
      radionuclide synovectomy (n=33) and corticosteroid instillation (n=7). The
      necessity of a repeat intervention was used as a criterion of successful
      treatment. RESULTS: In the group of surgical synovectomies, 22% of the patients
      required repeat operations, in the group of radiation synovectomy, this was 9%
      and, in the group treated with corticosteroids, this was 43%. The average
      hospitalisation time was 50 days for surgical procedures (19-133 days) and 7 days
      for radiation synovectomy procedures (4-13 days). DISCUSSION: In 1994 Merchan
      presented seven excellent or good results in a group of 10 knees evaluated 1 year
      after treatment with methylprednisolone. Six years later he reported that "five
      years after completion of treatment, all results of the observed patients were
      poor". Generally, corticosteroids will reduce synovitis in the majority of
      patients but the effect is temporary. A complete remission is a very rare
      situation under corticosteroid treatment. The experience with surgical
      synovectomies is not recent and this method is described as carrying a high risk
      of complications and requiring a high amount of coagulating factor consumption.
      There are several recent reports on the application of Yttrium-90: in Madrid they
      evaluated treated joints (knees, ankles and elbows, n = 66) in 44 patients aged
      from 9 to 39 years. The results were good in less than half of the knees and
      ankles. The treatment of elbows was more successful. It was recommended to
      perform synoviorthesis at the early stages of synovitis. In Israel, they reported
      that a decrease in the number of bleeding episodes was achieved in 80% of 115
      patients treated with Yttrium-90; in 15% of them, bleeding in the treated joints
      stopped completely. In Izmir, Yttrium was used in the treatment of knees, elbows,
      ankles and also shoulders in children and young adults (3-25 years). The method
      was found to be safe and effective. Brazilian authors have experience with the
      treatment of knees, ankles, elbows and shoulders too; they have concluded that
      this method represents an important resource for the treatment of chronic
      haemophilic synovitis and markedly reduces joint bleeding frequency and pain,
      irrespective of the radiographic stage and inhibitor status. While the European
      Association of Nuclear Medicine (EANM) recommend using 186Re-sulfide for
      treatment in medium-sized joints, Chinese authors have published a study
      comparing the effect of using three different doses of 186Re-sulfide in the
      treatment of chronic synovitis in knees. Their patients have received an amount
      of radionuclide according to the thickness of their synovial layer measured on
      MRI, with the result that 22 patients exhibited significant reduction in synovial
      thickness. A reduction in the number of bleeding episodes was reached in 71% of
      the patients within an 18-month period. No significant differences were found
      among the groups receiving different radioactivity doses. In Turkey, 35 elbows,
      26 ankles and two shoulders in 49 patients aged between 3 and 30 years were
      treated with 186Re. The patients were followed up from 6 months to 3 years. At 6
      months after the procedure, 81% of the elbows and 86% of the ankles with grade II
      synovitis were free from bleeding, as well as 53% and 44% of the elbows and
      ankles with grade III synovitis, respectively. CONCLUSIONS: Radiation synovectomy
      appears to be the method of choice in the treatment of recurrent bleeding in the
      joint cavity in people with haemophilia. The efficacy of surgical synovectomy is
      lower in comparison with radiation synovectomy. Risks associated with surgery and
      anaesthesia, the need of hospitalisation and a prolonged period of rehabilitation
      are bothering. On the contrary, the application of corticosteroids cannot be
      recommended as a good method to treat recurrent haemarthroses.

PMID- 24750968
TI  - [Tibio-talo-calcaneal arthrodesis with the retrograde intramedullary nail MEDIN].
AB  - PURPOSE OF THE STUDY: When the talus and the talocalcaneal joint are both
      affected, their fusion is the method of treatment. Ankle arthrodesis is carried
      out using various osteosynthetic materials such as external fixators, screws and
      plates. One of the options is retrograde nailing. Tibio-talo-calcaneal
      arthrodesis is frequently indicated in patients with rheumatoid arthritis (RA) in
      whom both the talus and the subtalar joint are often affected. MATERIAL AND
      METHODS: A retrograde nail for tibio-talo-calcaneal arthrodesis was developed at
      our department in cooperation with MEDIN Company. This is a titanium double
      curved nail, with the distal part bent at 8 degrees ventrally and 10 degrees
      laterally. It is inserted from the transfibular approach. RESULTS: Sixty-two
      patients, 35 women and 27 men, were treated at our department from 2005. Since
      one patient had bilateral surgery, 63 ankles were included. The indications for
      arthrodesis involved rheumatoid arthritis in 42, post-traumatic arthritis in 10,
      failed ankle arthrodesis in two and failed total ankle arthroplasty in five
      ankles; tibial stress fractures close above the ankle in two RA patients, one
      patient with dermatomyositis and one with lupus erythematodes. The average age at
      the time of surgery was 64.2 years (range, 30 to 80). The average follow-up was
      4.5 years (range, 1 to 9 years), Satisfaction with the treatment outcome and
      willingness to undergo surgery on the other side were reported by 82% of the
      patients. The AOFAS score improved from 35 to 74 points. Three (4.8%) patients
      complained of painful feet due to the fact that exact correction of the calcaneus
      was not achieved and the heel after arthrodesis remained in a slightly varus
      position. Of them, two had a failed total ankle arthroplasty. Post-operative
      complications included early infection managed by antibiotic treatment and early
      surgical revision with irrigation.in two (3.2%) RA patients, who were undergoing
      biological therapy. Late infection developed at 2 to 3 years after surgery in
      three (4.3%) patients (two had RA). The infection was managed by revision surgery
      with nail removal and irrigation. All patients healed well. Necrosis of the talus
      and development of a pseudoarthrosis were recorded in four (6.4%) patients, who
      subsequently underwent nail removal and repeat fusion using an external fixator.
      DISCUSSION: Retrograde nailing for tibio-talo-calcaneal arthrodesis is used by
      many authors. Its complication rate is comparable with the other methods of
      arthrodesis. CONCLUSIONS: The use of tibio-talo-calcaneal arthrodesis aims at a
      painless and stable joint. Arthrodesis of the talus and the subtalar joint using
      a retrograde nail is an effective surgical treatment of the joints affected. It
      is especially recommended for RA patients who have severe deviations. Retrograde
      nailing provides a stable osteosynthesis which does not require plaster cast
      immobilisation. The double-curved nail allows for its insertion in the solid part
      of the calcaneus and helps avoiding injury to the neurovascular bundle.

PMID- 24750969
TI  - Anatomically precontoured LCP for delayed union of a medial third clavicle
      fracture. Case report with review of the literature.
AB  - BACKGROUND: Fractures of the medial clavicle third are rare injuries. Even in
      case of significant fracture displacement, their therapeutic management has been
      nonoperative. Recently, surgical intervention has become mandatory for displaced
      fractures types to prevent non-union and functional complaints, but the optimal
      operative strategy is being discussed controversially. CASE PRESENTATION: We
      describe the case of a 63-year-old male patient with a significantly displaced
      medial clavicle fracture after failed conservative treatment resulting in
      restricted, painful shoulder function. The patient underwent open reduction and
      osteosynthesis with an anatomically precontoured locking compression plate (LCP).
      One year after surgery the patient is free of complaints and has returned to his
      preinjury activity level without any functional restrictions. CONCLUSION: As a
      not yet reported operative approach, anatomically preshaped locking plating seems
      to be an effective fixation method for displaced fractures of the medial clavicle
      third. The operative management is described in detail and discussed with the
      current literature. Based on the presented case, we underline the statement that
      displaced medial clavicle fractures should be surgically addressed to avoid late
      damage.

PMID- 24750970
TI  - [Posterior dislocation of the talus].
AB  - This report presents a rare case of an open total talar extrusion. The patient
      was treated by reduction and transarticular Kirschner-wire fixation of the talus,
      suture of an associated Achilles tendon rupture and plaster cast immobilisation.
      The plaster cast and Kirschner wires were removed after 6 weeks. At 10 weeks
      after injury, the patient started to walk with full weight-bearing of the
      operated extremity. At 18 months after injury, the patient was free from
      subjective complaints, with persisting slight restriction of ankle dorsiflexion
      range of motion and recurrent perimalleolar oedema. Neither MRI nor radiographic
      examination showed any avascular necrosis of the talus. The authors discuss the
      aetiology, diagnosis, therapeutic options and the most serious complications of
      this injury.

PMID- 24750971
TI  - Reducing the burden of suicide in the U.S.: the aspirational research goals of
      the National Action Alliance for Suicide Prevention Research Prioritization Task
      Force.
AB  - BACKGROUND: The National Action Alliance for Suicide Prevention Research
      Prioritization Task Force (RPTF) has created a prioritized national research
      agenda with the potential to rapidly and substantially reduce the suicide burden
      in the U.S. if fully funded and implemented. PURPOSE: Viable, sustainable
      scientific research agendas addressing challenging public health issues such as
      suicide often need to incorporate perspectives from multiple stakeholder groups
      (e.g., researchers, policymakers, and other end-users of new knowledge) during an
      agenda-setting process. The Stakeholder Survey was a web-based survey conducted
      and analyzed in 2011-2012 to inform the goal-setting step in the RPTF agenda
      development process. The survey process, and the final list of "aspirational"
      research goals it produced, are presented here. METHODS: Using a modified Delphi
      process, diverse constituent groups generated and evaluated candidate research
      goals addressing pressing suicide prevention research needs. RESULTS: A total of
      716 respondents representing 49 U.S. states and 18 foreign countries provided
      input that ultimately produced 12 overarching, research-informed aspirational
      goals aimed at reducing the U.S. suicide burden. Highest-rated goals addressed
      prevention of subsequent suicidal behavior after an initial attempt, strategies
      to retain patients in care, improved healthcare provider training, and generating
      care models that would ensure accessible treatment. CONCLUSIONS: The Stakeholder
      Survey yielded widely valued research targets. Findings were diverse in focus,
      type, and current phase of research development but tended to prioritize
      practical solutions over theoretical advancement. Other complex public health
      problems requiring input from a broad-based constituency might benefit from web
      based tools that facilitate such community input.

PMID- 24750972
TI  - Glycosylated hemoglobin and coronary artery disease in patients without diabetes
      mellitus.
AB  - BACKGROUND: Abnormal glucose metabolism is a major determinant of coronary artery
      disease (CAD) and mortality in developed countries. Glycosylated hemoglobin
      (HbA1c) is a more stable, accurate parameter of glucose homeostasis than fasting
      glycemia, thus providing prognostic information in diabetics. However, its role
      and relationship with CAD remains unclear in non-diabetics. PURPOSE: To evaluate
      the relationship between HbA1c and CAD in a consecutive cohort of patients
      without diabetes mellitus. METHODS: Non-diabetic patients undergoing coronary
      angiography between April 2007 and October 2012 were included. Additionally
      carotid intima-media thickness (C-IMT) was evaluated during hospitalization in a
      consecutive cohort of patients. RESULTS: 1,703 consecutive patients were included
      and divided according to HbA1c tertiles (<5.5%, 5.5%-5.79%, >=5.8%). HbA1c was
      associated with aging (p<0.001); hypercholesterolemia (p=0.01); renal failure
      (p=0.006); hypertension (p=0.002); previous myocardial infarction (p=0.004);
      previous percutaneous coronary intervention (p=0.01); indication to angiography
      (p=0.01); use of angiotensin receptor blockers (p=0.01); beta-blockers (p=0.03);
      nitrates (p=0.02); statins (p=0.008); calcium antagonists (p=0.01); diuretics
      (p<0.001); acetylsalicylic acid (p<0.001); baseline glycemia (p<0.001);
      triglycerides (p=0.02); and uric acid (p=0.04). HbA1c, but not fasting glycemia,
      was significantly associated with the prevalence of CAD (adjusted OR=1.51, 95%
      CI=1.15, 1.97, p=0.002), with 5.8% identified by the receiver operating
      characteristic (ROC) curve as the best cut-off value for CAD prediction. HbA1c
      was significantly associated with C-IMT and carotid plaques prevalence.
      CONCLUSIONS: Among non-diabetic patients, higher HbA1c even within the normal
      range is significantly associated with the risk of CAD. Future large studies are
      needed to evaluate whether more aggressive cardiovascular prevention can reduce
      the risk of CAD among patients with HbA1c >= 5.8%.

PMID- 24750973
TI  - Age-specific strategies for immunization reminders and recalls: a registry-based
      randomized trial.
AB  - BACKGROUND: Although previous studies have found reminder/recall to be effective
      in increasing immunization rates, little guidance exists regarding the specific
      ages at which it is optimal to send reminder/recall notices. PURPOSE: To assess
      the relative effectiveness of centralized reminder/recall strategies targeting
      age-specific vaccination milestones among children in urban areas during June
      2008-June 2009. METHODS: Three reminder/recall strategies used capabilities of
      the Michigan Care Improvement Registry (MCIR), a statewide immunization
      information system: a 7-month recall strategy, a 12-month reminder strategy, and
      a 19-month recall strategy. Eligible children were randomized to notification
      (intervention) or no notification groups (control). Primary study outcomes
      included MCIR-recorded immunization activity (administration of >=1 new dose,
      entry of >=1 historic dose, entry of immunization waiver) within 60 days
      following each notification cycle. RESULTS: A total of 10,175 children were
      included: 2,072 for the 7-month recall, 3,502 for the 12-month reminder, and
      4,601 for the 19-month recall. Immunization activity was similar between
      notification versus no notification groups at both 7 and 12 months. Significantly
      more 19-month-old children in the recall group (26%) had immunization activity
      compared to their counterparts who did not receive a recall notification (19%).
      CONCLUSIONS: Although recall notifications can positively affect immunization
      activity, the effect may vary by targeted age group. Many 7- and 12-month-olds
      had immunization activity following reminder/recall; however, levels of activity
      were similar irrespective of notification, suggesting that these groups were
      likely to receive medical care or immunization services without prompting.

PMID- 24750974
TI  - Bovine leukemia virus DNA in human breast tissue.
AB  - Bovine leukemia virus (BLV), a deltaretrovirus, causes B-cell leukemia/lymphoma
      in cattle and is prevalent in herds globally. A previous finding of antibodies
      against BLV in humans led us to examine the possibility of human infection with
      BLV. We focused on breast tissue because, in cattle, BLV DNA and protein have
      been found to be more abundant in mammary epithelium than in lymphocytes. In
      human breast tissue specimens, we identified BLV DNA by using nested liquid-phase
      PCR and DNA sequencing. Variations from the bovine reference sequence were
      infrequent and limited to base substitutions. In situ PCR and immunohistochemical
      testing localized BLV to the secretory epithelium of the breast. Our finding of
      BLV in human tissues indicates a risk for the acquisition and proliferation of
      this virus in humans. Further research is needed to determine whether BLV may
      play a direct role in human disease. 

PMID- 24750975
TI  - Histopathological characteristics of microfocal prostate cancer detected during
      systematic prostate biopsy.
AB  - OBJECTIVE: To evaluate the prevalence of adverse pathological features and the
      percentage of multifocal and/or bilateral disease in a series of patients who
      underwent radical prostatectomy (RP) for unique, microfocal prostate cancer
      (miPCa) detected on prostate biopsy in the pre-active surveillance (AS) era.
      PATIENTS AND METHODS: In this retrospective, multi-institutional study, we
      analysed the clinical records of 131 consecutive patients who underwent either
      retropubic or robot-assisted RP for miPCa at two referral centres from January
      2000 to December 2011. miPCa was defined as a neoplastic lesion present in <=10%
      of core with biopsy Gleason score not applicable or biopsy Gleason score 6.
      RESULTS: There were 17 (13%) pT3-4 prostate cancers and a single case (0.8%) of
      pN+ tumour. Moreover, 31 (24.1%) patients had a Gleason score of >6 in the RP
      specimen. Therefore, unfavourable pathological features (pT3-4/N+ and/or Gleason
      score >6) were present in 40 (30.5%) patients. The median (interquartile range)
      prostate-specific antigen (PSA) density was 0.11 (0.09-0.17) and 0.16 (0.11-0.24)
      ng/mL/mL in patients with favourable and unfavourable pathological
      characteristics, respectively (P = 0.003). The receiver operating characteristic
      curve had an area under the curve value of 0.67 (95% confidence interval 0.56
      0.77) for PSA density to predict the risk of unfavourable pathological features.
      CONCLUSION: Patients with miPCa who are candidates for an AS protocol should be
      adequately informed that in ~30% of cases the cancer might be locally advanced
      and/or with a Gleason score of >6. Those unfavourable pathological
      characteristics could be predicted by the PSA density value. Further studies
      should investigate the role of a more extensive biopsy sampling to reduce the
      risk of under-staging and/or under-grading in patients with an initial diagnosis
      of miPCa.

PMID- 24750976
TI  - Beacon-based (bbFISH(r)) technology for rapid pathogens identification in blood
      cultures.
AB  - BACKGROUND: Diagnosis and treatment of bloodstream infections (BSI) are often
      hampered by the delay in obtaining the final results of blood cultures. Rapid
      identification of pathogens involved in BSI is of great importance in order to
      improve survival of septic patients. Beacon-based fluorescent in situ
      hybridization (hemoFISH(r) Gram positive and hemoFISH(r) Gram negative test kits,
      miacom diagnostics GmbH Dusseldorf, Germany) accelerates the identification of
      most frequent bacterial pathogens of sepsis. RESULTS: In this study a total of
      558 blood culture (377 blood culture positive and 181 negative) were tested with
      the hemoFISH(r) method and the results were evaluated in comparison with the
      traditional culture based methods. The overall sensitivity and specificity of the
      hemoFISH(r) tests were 94.16% and 100%, while, the PPV and NPV were 100 and
      89.16%, respectively. As the hemoFISH(r) results were obtained within 45 mins,
      the time difference between the final results of the traditional culture method
      and the hemoFISH(r) assay was about two days. CONCLUSIONS: Considering the good
      sensitivity and specificity of the hemoFISH(r) assays as well as the significant
      time saving in obtaining the final results (p-value 0.0001), the introduction of
      the system could be rialable in the microbiology laboratories, even alongside the
      traditional systems.

PMID- 24750977
TI  - beta-adrenergic receptor blockers in hypertension.

PMID- 24750978
TI  - beta-Blockers in hypertension: studies and meta-analyses over the years.
AB  - beta-Blockers are among the most commonly used medications in the treatment of
      hypertension. However, 45 years after their initial indication for that
      treatment, their place in the treatment of hypertensive patients is under
      evaluation and their usefulness has been questioned based on evidence from meta
      analyses of clinical trials. The beta-blocker class consists of various agents
      with diverse pharmacokinetic and pharmacodynamic properties including lipo- and
      hydrophilicity, duration of action, intrinsic sympathomimetic activity,
      vasodilation, and metabolism linked to genetic polymorphisms. Because of their
      various properties, some beta-blockers are indicated for cardiovascular
      conditions such as angina, rate control of atrial fibrillation, chronic heart
      failure, and after myocardial infarction, and other indications such as migraine
      and essential tremor. There have been more than 17 large trials influencing the
      recommendations on the use of these agents in the treatment of hypertension. The
      results of these trials initially led to the widespread recommendation for the
      use of beta-blockers in the management of hypertension. However, the recent
      multiple meta-analyses using these trials have raised a controversy on their
      place in that treatment. The Canadian Hypertension Education Program
      recommendations have included beta-blockers as a first-line treatment option for
      patients younger than 60 years of age based on the evidence from these large
      trials, and this has been supported by 2 of the meta-analyses. This article
      reviews these studies to help clinicians better understand the role of beta
      blockers in managing hypertension. 

PMID- 24750979
TI  - Central blood pressure as an index of antihypertensive control: determinants and
      potential value.
AB  - The measurement of central blood pressure has generated interest as a tool in
      predicting cardiovascular events. The purpose of this article is to review the
      meaning and measurement of the central blood pressure and consider its potential
      value as an index of the antihypertensive response. Indirect estimation of
      central aortic pressures is obtained by the study of the radial pulse wave
      compared with a central pulse wave contour measured at the carotid or femoral
      artery level. The sum of the forward pressure wave created by ventricular
      contraction and of the reflected pressure wave from the peripheral arterial
      system produce the peak systolic blood pressure in the aorta. Measurement of the
      peripheral reflected-wave contribution to aortic blood pressure can be quantified
      as the augmentation index. Also, the increase in the rapidity of this travelling
      wave can be measured as the pulse wave velocity. These 2 parameters are
      considered to be valid indices of the peripheral arterial stiffness. Along with
      the calculation of systolic and diastolic aortic pressures, these measurements
      can give a better understanding of the actual central blood pressure to which
      core organs like heart, brain, and kidneys are submitted. There is tantalizing
      evidence for the potential value of central blood pressure as a useful index of
      antihypertensive action, but until clear evidence is obtained, its use should
      continue to be considered exploratory. 

PMID- 24750980
TI  - Nebivolol: vasodilator properties and evidence for relevance in treatment of
      cardiovascular disease.
AB  - beta-adrenergic blocking agents, a pharmacologically diverse class of
      cardiovascular medications, are recommended as first-line treatment for patients
      with hypertension and concomitant structural heart disease, and for angina and
      heart failure. Many within-class differences exist, from pharmacokinetics and
      pharmacodynamics to ancillary effects, such as intrinsic sympathomimetic
      activity, antiarrhythmic activity, alpha-1 adrenergic receptor blockade affinity,
      and direct vasodilation. Nebivolol is a third-generation, beta1 selective, long
      acting beta-blocker, which causes direct vasodilation via endothelium-dependent
      nitric oxide stimulation. The vasodilatory actions of nebivolol might result in
      clinical effects with some distinct properties. Differences from other beta
      blockers might include improvement of endothelial function, enhancement of
      forward flow in muscular resistance arteries, maintenance of exercise tolerance,
      and overall improved tolerability, side effect profile, and adherence. Nebivolol
      has been shown to be a clinically effective beta-blocker for treatment as initial
      or add-on therapy for systemic hypertension, as an antianginal agent, and as
      therapy for patients with heart failure. These properties position nebivolol as a
      treatment option for patients with hypertension and/or structural heart disease,
      although its precise role in the therapeutic armamentarium remains to be
      clarified. 

PMID- 24750981
TI  - Atenolol vs nonatenolol beta-blockers for the treatment of hypertension: a meta
      analysis.
AB  - BACKGROUND: Previous reviews have shown that beta-blocker use for the treatment
      of hypertension without compelling indications was associated with increased risk
      of stroke in the elderly. It remains unclear whether this increased risk was
      driven by the type of beta-blocker. We sought to compare the efficacy of atenolol
      vs nonatenolol beta-blockers in clinical trials enrolling young (< 60 years) and
      older patients with hypertension. METHODS: The Cochrane and MEDLINE databases
      were searched (January 2006-May 2013) for randomized trials evaluating stroke,
      myocardial infarction, death, or composite cardiovascular end points. Twenty-one
      hypertension trials with data on 145,811 participants were identified: 15 used
      atenolol, 7 were placebo-controlled trials, and 14 were active comparator trials.
      There were no trials of newer generation beta-blockers identified. RESULTS: Among
      the elderly, atenolol was associated with an increased risk of stroke (relative
      risk [RR], 1.17; 95% confidence interval [CI], 1.05-1.30) compared with other
      antihypertensive agents. The risk of stroke for nonatenolol beta-blockers
      compared with other agents (RR, 1.22; 95% CI, 0.99-1.50) did not reach
      statistical significance in the elderly. In the young, atenolol was associated
      with reduced risk of stroke compared with other agents (RR, 0.78; 95% CI, 0.64
      0.95), whereas nonatenolol beta-blockers were associated with a lower risk of
      composite cardiac events (RR, 0.86; 95% CI, 0.75-0.996) compared with placebo,
      with no significant difference in events compared with active controls.
      CONCLUSIONS: In the young, both atenolol and nonatenolol beta-blockers are
      effective in reducing cardiovascular end points for hypertension without
      compelling indications. Atenolol is associated with increased stroke in the
      elderly but whether this extends to nonatenolol beta-blockers remains uncertain.

PMID- 24750982
TI  - The trabecula septomarginalis (Leonardo's cord) in abnormal ventriculo-arterial
      connections: anatomic and morphogenetic implications.
AB  - BACKGROUND: The abnormal ventriculo-arterial connections in atrio-ventricular
      concordance and situs solitus with two well developed ventricles include the
      range from tetralogy of Fallot throughout the different forms of double outlet
      right ventricle to transposition of great arteries.The infundibular septum and
      the trabecula septomarginalis are the fundamental anatomical landmarks for the
      segmental analysis.In these abnormalities there is a pathological progressive
      counter-clockwise rotation of the infundibular septum which divorces from the
      antero-superior limb of the trabecula septomarginalis and achieves his identity.
      Is there any anatomical evidence of a simultaneous abnormal counter-clockwise
      rotation of the trabecula septomarginalis? METHODS: Malposition of great arteries
      is a generic term since all relationships have to be expected.We present
      specimens with anatomical evidence of a progressive counter-clockwise rotation
      from 0 degrees  to about 180 degrees of the plane passing throughout the
      trabecula septomarginalis's limbs. RESULTS: We can observe sequentially:1.
      Malformations in which the posterior limb of the trabecula septomarginalis is
      committed to the ventriculo infundibular fold: (tetralogy of Fallot, double
      outlet right ventricle with sub-aortic ventricular septal defect, truncus
      arteriosus and doubly committed ventricular septal defect);2. Malformations in
      which the posterior limb of the trabecula septomarginalis is committed to the
      infundibular septum (double outlet right ventricle with sub-pulmonary ventricular
      septal defect, transposition of great arteries). CONCLUSIONS: 1. The sequential
      segmental analysis identify all the morphologies.2. The trabecula septomarginalis
      plane presents a progressive counter-clockwise twist on the long axis.3. Since
      the trabeculated portions of the ventricles are the oldest developmental
      components, our observations support the hypothesis that the abnormal ventriculo
      arterial connections could be in relation with a pathological myocardial process
      during early cardio-genesis.We are promoting new studies to investigate our
      anatomical observations.

PMID- 24750983
TI  - Hospital variation in sphincter preservation for elderly rectal cancer patients.
AB  - BACKGROUND: The primary goal of an operation for rectal cancer is to cure cancer
      and, where possible, preserve continence. A wide range of sphincter preservation
      rates have been reported. This study evaluated hospital variation in the use of
      low anterior resection (LAR), local excision (LE), and abdominoperineal resection
      (APR) in the treatment of elderly rectal cancer patients. METHODS: Using
      Surveillance, Epidemiology, and End Results-Medicare linked data, we identified
      4959 patients older than 65 y with stage I-III rectal cancer diagnosed from 2000
      2005 who underwent operative intervention at one of 370 hospitals. We evaluated
      the distribution of hospital-specific procedure rates and used generalized mixed
      models with random hospital effects to examine the influence of patient
      characteristics and hospital on operation type, using APR as a reference.
      RESULTS: The median hospital performed APR on 33% of elderly patients with rectal
      cancer. Hospital was a stronger predictor of LAR receipt than any patient
      characteristic, explaining 32% of procedure choice, but not a strong predictor of
      LE, explaining only 3.8%. Receipt of LE was primarily related to tumor size and
      tumor stage, which combined explained 31% of procedure variation. CONCLUSIONS:
      Receipt of LE is primarily determined by patient characteristics. In contrast,
      the hospital where surgery is performed significantly influences whether a
      patient undergoes an LAR or APR. Understanding the factors that cause this
      institutional variation is crucial to ensuring equitable availability of
      sphincter preservation.

PMID- 24750984
TI  - Ginsenoside Rg1 protects mouse liver against ischemia-reperfusion injury through
      anti-inflammatory and anti-apoptosis properties.
AB  - BACKGROUND: Ginsenoside Rg1, the major effective component of ginseng, possesses
      a variety of pharmacologic activities. The objective of this study was to
      investigate the effects of Rg1 on liver ischemia-reperfusion (IR) injury and
      explore its potential mechanisms. MATERIALS AND METHODS: Liver warm IR injury was
      achieved by occluding the portal vein and hepatic artery for 1 h followed by 6-h
      reperfusion. Eighteen mice were equally randomized into three groups: sham group,
      IR group, and IR plus Rg1 group (n = 6 mice per group). Mice received an
      intravenous dose of 20 mg/kg Rg1 or an equivalent volume of saline before
      ischemic insult. Liver samples and serum were collected for analyses. Serum
      aminotransferase, histopathology, and apoptosis were determined. Cytokines were
      measured by real-time quantitative reverse transcription polymerase chain
      reaction (qRT-PCR). The phosphorylation of nuclear factor kappa B (NF-kappaB) p65
      was assessed by Western blotting. In addition, the effect of Rg1 in a simulated
      IR model in vitro was also investigated. Rg1 (100 ug/mL and 500 ug/mL) was
      administered 1 h before hypoxia insult, and then apoptosis was measured after 12
      h reperfusion. RESULTS: Liver IR injury led to a dramatic increase in
      aminopherase activity, apoptosis and necrosis of hepatocytes, and production of
      proinflammatory cytokines. Pretreatment with Rg1 protected mice from IR-induced
      liver injury. Treatment with a high-dose Rg1 (500 ug/mL) significantly suppressed
      apoptosis compared with a lower dose or control (both P < 0.001). Phosphorylation
      of NF-kappaB p65 was increased significantly in IR group, and administration with
      Rg1 suppressed the level of phosphorylation. CONCLUSIONS: Pretreatment of mice
      with Rg1 reduced hepatocellular apoptosis and inhibited inflammatory response,
      which was in part through the NF-kappaB signaling pathway. Rg1 may provide a
      novel therapeutic strategy for the treatment of IR-induced liver injury.

PMID- 24750985
TI  - Perioperative changes in trunk musculature and postoperative outcomes.
AB  - BACKGROUND: Surgeons often face difficult decisions in selecting which patients
      can tolerate major surgical procedures. Although recent studies suggest the
      potential for trunk muscle size, as measured on preoperative imaging, to inform
      surgical risk, these measures are static and do not account for the effect of the
      surgery itself. We hypothesize that trunk muscle size will show dynamic changes
      over the perioperative period, and this change correlates with postoperative
      mortality risk. METHODS: A total of 425 patients who underwent inpatient general
      surgery were identified to have both a 90-d preoperative and a 90-d postoperative
      abdominal computed tomography scan. The change in trunk muscle size was
      calculated using analytic morphomic techniques. The primary outcome was 1-y
      survival. Covariate-adjusted outcomes were assessed using multivariable logistic
      regression. RESULTS: A total of 82.6% patients (n = 351) experienced a decrease
      in trunk muscle size in the time between their scans (average 62.1 d). When
      stratifying patients into tertiles of rate of change in trunk muscle size and
      adjusting for other covariates, patients in the tertile of the greatest rate loss
      had significantly increased risk of 1-y mortality than those in the tertile of
      the least rate loss (P = 0.002; odds ratio = 3.40 95% confidence interval, 1.55
      7.47). The adjusted mortality rate for the tertile of the greatest rate loss was
      24.0% compared with 13.3% for the tertile of the least decrease. CONCLUSIONS:
      Trunk muscle size changes rapidly in the perioperative period and correlates with
      mortality. Trunk muscle size may be a critical target for interventional programs
      focusing on perioperative optimization of the surgical patient.

PMID- 24750987
TI  - Participation of hypertension patients in early-phase clinical trials.

PMID- 24750986
TI  - Identifying predictors of a difficult thyroidectomy.
AB  - BACKGROUND: A Thyroidectomy Difficulty Scale (TDS) was previously developed that
      identified more difficult operations, which correlated with longer operative
      times and higher complication rates. The purpose of this study was to identify
      preoperative variables predictive of a more difficult thyroidectomy using the
      TDS. METHODS: A four item, 20-point TDS, was used to score the difficulty of
      thyroid operations. Patient and disease factors were recorded for each patient.
      Difficult thyroidectomy and non-difficult thyroidectomy (NDT) patients were
      compared. A final multivariate logistic regression model was constructed with
      significant (P<0.05) variables from a univariate analysis. RESULTS: A total of
      189 patients were scored using TDS. Of them, 69 (36.5%) suffered from
      hyperthyroidism, 42 (22.2%) from Hashimotos, 34 (18.0%) from thyroid cancer, and
      36 (19.0%) from multinodular goiter. Among hyperthyroid patients, the DT group
      had a greater number preoperatively treated with Lugols potassium iodide (81.6%
      DT versus 58.1% NDT, P=0.032), presence of ophthalmopathy (31.6% DT versus 9.7%
      NDT, P=0.028), and presence of (>4 IU/mL) antithyroglobulin antibodies (34.2% DT
      versus 12.9% NDT, P=0.05). Using multivariate analysis, hyperthyroidism (odds
      ratio [OR], 4.35, 95% confidence interval [CI], 1.23-15.36, P=0.02), presence of
      antithyroglobulin antibody (OR, 3.51, 95% CI, 1.28-9.66, P=0.015), and high (>150
      ng/mL) thyroglobulin (OR, 2.61, 95% CI, 1.06-6.42, P=0.037) were independently
      associated with DT. CONCLUSIONS: Using TDS, we demonstrated that a diagnosis of
      hyperthyroidism, preoperative elevation of serum thyroglobulin, and
      antithyroglobulin antibodies are associated with DT. This tool can assist
      surgeons in counseling patients regarding personalized operative risk and improve
      OR scheduling.

PMID- 24750988
TI  - Responses to threat of influenza A(H7N9) and support for live poultry markets,
      Hong Kong, 2013.
AB  - We conducted a population survey in Hong Kong to gauge psychological and
      behavioral responses to the threat of influenza A(H7N9) and support for closure
      of live poultry markets. We found low anxiety and low levels of exposure to live
      poultry but mixed support for permanent closure of the markets. 

PMID- 24750989
TI  - SafeNet: a methodology for integrating general-purpose unsafe devices in safe
      robot rehabilitation systems.
AB  - Robot-assisted neurorehabilitation often involves networked systems of sensors
      ("sensory rooms") and powerful devices in physical interaction with weak users.
      Safety is unquestionably a primary concern. Some lightweight robot platforms and
      devices designed on purpose include safety properties using redundant sensors or
      intrinsic safety design (e.g. compliance and backdrivability, limited exchange of
      energy). Nonetheless, the entire "sensory room" shall be required to be fail-safe
      and safely monitored as a system at large. Yet, sensor capabilities and control
      algorithms used in functional therapies require, in general, frequent updates or
      re-configurations, making a safety-grade release of such devices hardly
      sustainable in cost-effectiveness and development time. As such, promising
      integrated platforms for human-in-the-loop therapies could not find clinical
      application and manufacturing support because of lacking in the maintenance of
      global fail-safe properties. Under the general context of cross-machinery safety
      standards, the paper presents a methodology called SafeNet for helping in
      extending the safety rate of Human Robot Interaction (HRI) systems using unsafe
      components, including sensors and controllers. SafeNet considers, in fact, the
      robotic system as a device at large and applies the principles of functional
      safety (as in ISO 13489-1) through a set of architectural procedures and
      implementation rules. The enabled capability of monitoring a network of unsafe
      devices through redundant computational nodes, allows the usage of any custom
      sensors and algorithms, usually planned and assembled at therapy planning-time
      rather than at platform design-time. A case study is presented with an actual
      implementation of the proposed methodology. A specific architectural solution is
      applied to an example of robot-assisted upper-limb rehabilitation with online
      motion tracking. 

PMID- 24750990
TI  - Use of statin during hospitalization improves the outcome after intracerebral
      hemorrhage.
AB  - AIMS: To examine the relationship between statin use in Chinese patients with
      intracerebral hemorrhage (ICH) during their hospitalization and the outcomes.
      METHODS: Data were collected from the China National Stroke Registry. Good
      functional outcome was defined by a modified Rankin Scale score between 0-2.
      Functional outcome and rate of mortality at 3 months and 1 year were compared
      between ICH patients on statin and those without it during their hospitalization.
      Odds ratios (ORs) with 95% confidence intervals (CI) were calculated using the
      multivariable logistic regression model adjusted for baseline risk factors.
      RESULTS: Among 3218 consecutive ICH patients from 2007 to 2008, 220 (6.8%) were
      on statin during their hospitalization. Compared with those without statin,
      patients on statin were younger, had more stroke risk factors but lower stroke
      severity. ICH patients on statin had better functional outcome at 3 months (OR
      2.24, 95% CI 1.49-3.36) and at 1 year (OR 2.04, 95% CI 1.37-3.06). They also had
      lower rate of mortality at 3 months (OR 0.44, 95% CI 0.22-0.87) and 1 year (OR
      0.49, 95% CI 0.27-0.86). CONCLUSIONS: In-hospital statin use in ICH patients is
      associated with better functional outcome and lower mortality at 3 months and 1
      year.

PMID- 24750991
TI  - Synthesis and antitubercular screening of [(2-chloroquinolin-3-yl)methyl]
      thiocarbamide derivatives.
AB  - A series of 1-(substituted-phenyl)-1-[(2-chloroquinolin-3-yl)methyl]thiocarbamide
      and 1-(substituted-phenyl)-1-[(2-chloroquinolin-3-yl)methyl]methylthiocarbamide
      derivatives was synthesized as antitubercular agent. The structure of quinolinyl
      amines and their thiocarbamide derivatives were established on the basis of IR,
      (1)H and (13)C-NMR and mass spectral data. All the compounds were tested in vitro
      for antimycobacterial activity against Mycobacterium tuberculosis (ATCC-25177) in
      Lowenstein-Jensen medium by well diffusion method and MIC by twofold serial
      dilution method. Results of the antitubercular screening revealed that compounds
      showed moderate to good antitubercular activity. Compound having two halogens in
      the phenyl rings viz. 3g, 3h, 4g, and 4h exhibited MIC of 50 MUg/mL. The
      computational parameters relevant to absorption and permeation of target
      compounds were also calculated and found to be well correlated with
      antitubercular activity.

PMID- 24750992
TI  - Direct intrawound administration of dimethylsulphoxide relieves acute pain in
      rats.
AB  - Wounds associated with injuries such as burns can produce moderate to severe
      pain. Besides causing distress to the patient, unrelieved pain could delay
      healing owing to stress-related problems. Thus, pain needs to be treated as early
      as possible after injury. It was hypothesised that local treatment of wounds with
      appropriate analgesic drugs could attenuate pain. HOE 140, a bradykinin receptor
      antagonist, reduced acute inflammatory pain in rats after intrawound
      administration. In this study, the analgesic effect of dimethylsulphoxide (DMSO)
      was investigated in a similar hind-paw incision model in rats. An extremely small
      quantity (10 ul) of 100% DMSO was administered into the incision site just before
      closure of the wound. It persistently attenuated guarding behaviour in rats over
      a period of 3 days without affecting thermal hyperalgesia or allodynia.
      Accumulated evidence indicates that guarding is equivalent to pain at rest in
      humans. The possible mechanisms of the analgesic effect could be inhibition of C
      group of peripheral nerve fibres or even free radical scavenging. Healing of the
      wound was found to be normal at the end of the study period. In conclusion, DMSO
      could be useful in the treatment of acute pain resulting from tissue injuries
      such as burns. 

PMID- 24750993
TI  - The influence of Wickerhamomyces anomalus killer yeast on the fermentation and
      chemical composition of apple wines.
AB  - The aim of this study was to determine the influence of two different
      Wickerhamomyces anomalus strains, CBS 1982 and CBS 5759, on the chemical
      composition and sensory characteristics of Gloster apple wines. They were
      inoculated into unpasteurized as well as pasteurized apple musts together with a
      S. cerevisiae strain as a mixed culture. Fermentation kinetics, basic enological
      parameters, antioxidant properties as well as selected polyphenol, volatile
      compound, and organic acid contents were analyzed during the experiments. Apple
      wines obtained after spontaneous fermentation were characterized by high volatile
      acidity, increased concentrations of acetaldehyde, and volatile esters, as well
      as the lowest amounts of ethyl alcohol and higher alcohols compared with other
      samples. Addition of 0.05 g L(-1) W. anomalus killer strains to the unpasteurized
      must significantly changed the fermentation kinetics and chemical composition of
      apple wines. The value of volatile acidity was highly decreased, while the amount
      of higher alcohols and titratable acidity increased. Pasteurization of must
      improved the fermentation efficiency. Higher amounts of polyphenol compounds and
      lower amounts of malic acid were also detected. Application of W. anomalus
      strains together with S. cerevisiae yeast as a mixed culture positively
      influenced the chemical composition and sensory features of produced apple wines.

PMID- 24750994
TI  - Oxysterols.

PMID- 24750995
TI  - Quality of total mesorectal excision and depth of circumferential resection
      margin in rectal cancer: a matched comparison of the first 20 robotic cases.
AB  - AIM: There are concerns about the impact of robotic proctectomy on the quality of
      total mesorectal excision (TME) and the impact of laparoscopic proctectomy on the
      depth of the circumferential resection margin (CRM). The aim of this study was to
      compare the first 20 consecutive robotic proctectomies performed in our unit with
      matched series of open and laparoscopic proctocolectomy performed by the same
      surgeon. METHOD: Data on the first 20 consecutive patients treated with robotic
      proctectomy for rectal cancer, <12 cm from the anal verge, by the senior author
      (RB) were extracted from a prospectively maintained database. Groups of patients
      treated with open and laparoscopic proctectomy, matched for age, gender and body
      mass index (BMI) with those undergoing robotic proctectomy, were selected. The
      quality of the TME was judged as complete, nearly complete or incomplete. CRM
      clearance was reported in millimetres. Physiological parameters and operative
      severity were assessed. RESULTS: Age (P = 0.619), Physiological and Operative
      Severity Score for the Enumeration of Morbidity and Mortality (POSSUM) score (P =
      0.657), operative severity score (P = 0.977), predicted mortality (P = 0.758),
      comorbidities (P = 0.427), previous abdominal surgery (P = 0.941), tumour height
      (P = 0.912), location (P = 0.876), stage (P = 0.984), neoadjuvant chemoradiation
      (P = 0.625), operating time (P = 0.066), blood loss (P = 0.356), ileostomy (P =
      0.934), conversion (P = 0.362), resection type (P = 1.000), flatus (P = 0.437),
      diet (P = 0.439), length of hospital stay (P = 0.978), complications (P = 0.671),
      reoperations (P = 0.804), reinterventions (P = 0.612), readmissions (P = 0.349),
      tumour size (P = 0.542; P = 0.532; P = 0.238), distal margin (P = 0.790), nodes
      harvested (P = 0.338) and pathology stage (P = 0.623) did not differ among the
      three groups. The quality of TME showed a trend to be lower following robotic
      surgery, although this was not statistically significant [open 95/5/15
      (complete/nearly complete/incompete) vs laparoscopic 95/5/15 vs robotic 80/5/15;
      P = 0.235], but the degree of clearance at the CRM was significantly greater in
      robotic patients [open 8 (0-30) mm vs laparoscopic 4 (0-30) mm vs robotic 10.5 (1
      30) mm; P = 0.02]. CONCLUSION: The study reports no statistically significant
      difference between open and laparoscopic techniques in the quality of TME during
      the learning curve of robotic proctectomy for rectal cancer and demonstrates an
      improved CRM.

PMID- 24750996
TI  - Optimized method for ureteric reconstruction in a mouse kidney transplant model.
AB  - BACKGROUND: Murine kidney transplantation is an important model for studies of
      transplantation immunobiology. The most challenging aspect of the difficult
      surgical procedure is the ureteric anastomosis. METHODS: Two different approaches
      to ureteric reconstruction are compared here. Method 1, Patch: this involves
      anastomosis of the donor ureter together with a patch of donor bladder to
      recipient bladder. Method 2, Implant: this utilizes a 5-0 suture to pull the
      ureter through the bladder wall. The ureter's peripheral tissue is then fixed to
      the bladder wall at the implant site with 10-0 micro-sutures. RESULTS: In animals
      transplanted with the patch method, the initial success rate, defined as survival
      up to the third post-operative day, was 79% (n = 62), whereas the initial success
      rate for the implant method was 86.1% (n = 101; P = 0.28). The death rate from
      unknown and/or unspecified causes in the initial period was 16.1% (10/62) for the
      patch method, and 8.9% (9/101) for the implant method (P = 0.21). The average
      donor/recipient operation time with the implant method was 14.8 +/- 2.2/61.4 +/-
      4.7 min (76 min per transplant), whereas operation time with the patch method was
      28.3 +/- 2.4/77.8 +/- 5.5 min (106 min per transplant; P < 0.001). The ureteric
      implant method resulted in a lower rate of urinary leak compared with the patch
      method (1.1% versus 10.2%; P = 0.02). CONCLUSIONS: The ureteric implant method
      for mouse kidney transplantation is a reliable approach with at least as high a
      success rate as the bladder patch method and with a shorter operation time.

PMID- 24750997
TI  - Trends in infectious disease mortality rates, Spain, 1980-2011.
AB  - Using mortality data from National Institute of Statistics in Spain, we analyzed
      trends of infectious disease mortality rates in Spain during 1980-2011 to provide
      information on surveillance and control of infectious diseases. During the study
      period, 628,673 infectious disease-related deaths occurred, the annual change in
      the mortality rate was -1.6%, and the average infectious disease mortality rate
      was 48.5 deaths/100,000 population. Although the beginning of HIV/AIDS epidemic
      led to an increased mortality rate, a decreased rate was observed by the end of
      the twentieth century. By codes from the International Classification of
      Diseases, 9th revision, the most frequent underlying cause of death was
      pneumonia. Emergence and reemergence of infectious diseases continue to be public
      health problems despite reduced mortality rates produced by various
      interventions. Therefore, surveillance and control systems should be reinforced
      with a goal of providing reliable data for useful decision making. 

PMID- 24750998
TI  - Parasitic polymorphism of Coccidioides spp.
AB  - BACKGROUND: Coccidioides spp. is the ethiological agent of coccidioidomycosis, an
      infection that can be fatal. Its diagnosis is complicated, due to that it shares
      clinical and histopathological characteristics with other pulmonary mycoses.
      Coccidioides spp. is a dimorphic fungus and, in its saprobic phase, grows as a
      mycelium, forming a large amount of arthroconidia. In susceptible persons,
      arthroconidia induce dimorphic changes into spherules/endospores, a typical
      parasitic form of Coccidioides spp. In addition, the diversity of mycelial
      parasitic forms has been observed in clinical specimens; they are scarcely known
      and produce errors in diagnosis. METHODS: We presented a retrospective study of
      images from specimens of smears with 15% potassium hydroxide, cytology, and
      tissue biopsies of a histopathologic collection from patients with
      coccidioidomycosis seen at a tertiary-care hospital in Mexico City. RESULTS: The
      parasitic polymorphism of Coccidioides spp. observed in the clinical specimens
      was as follows: i) spherules/endospores in different maturation stages; ii)
      pleomorphic cells (septate hyphae, hyphae composed of ovoid and spherical cells,
      and arthroconidia), and iii) fungal ball formation (mycelia with septate hyphae
      and arthroconidia). CONCLUSIONS: The parasitic polymorphism of Coccidioides spp.
      includes the following: spherules/endospores, arthroconidia, and different forms
      of mycelia. This knowledge is important for the accurate diagnosis of
      coccidioidomycosis. In earlier studies, we proposed the integration of this
      diversity of forms in the Coccidioides spp. parasitic cycle. The microhabitat
      surrounding the fungus into the host would favor the parasitic polymorphism of
      this fungus, and this environment may assist in the evolution toward parasitism
      of Coccidioides spp.

PMID- 24750999
TI  - Niclosamide enhances ROS-mediated cell death through c-Jun activation.
AB  - Radiotherapy is an effective treatment modality in the clinical treatment of
      cancers, and has been combined with chemotherapy in order to improve therapeutic
      efficacy. Therefore, we aimed to develop small molecules that enhance the
      cytotoxic effects of radiotherapy. In this study, we provide evidence that
      niclosamide is an effective radiosensitizer in non-small cell lung cancer cells.
      Using a cell-based high-throughput viability screen of 1040 compounds in
      combination with gamma-ionizing radiation (IR), we found niclosamide, an FDA
      approved antihelminthic agent, had a radiosensitizing effect on H1299 human lung
      cancer cells. Pretreatment with niclosamide enhanced IR- induced cell death of
      H1299 in a dose-dependent manner via apoptosis compared with IR or niclosamide
      alone. The combined treatment induced significantly more phosphorylation of p38
      MAPK and c-Jun in H1299 cells than IR or niclosamide alone. Since IR induces
      apoptosis through generation of reactive oxygen species (ROS), hydrogen peroxide
      (H2O2) was employed as another ROS generator and we found that niclosamide also
      sensitized cells to H2O2. Niclosamide pretreatment also induced c-Jun and its
      phosphorylation in the presence of H2O2, thereby enhancing apoptosis. N-acetyl-L
      cysteine (NAC) treatment abolished both cell death and c-Jun activation induced
      by the combination treatments. Knockdown of c-Jun also decreased PARP cleavage
      and clonogenic cell survival in niclosamide- and IR-treated H1299 cells. Our
      findings suggest that niclosamide could be a promising radiosensitizer in lung
      cancer patients through activation of the p38 MAPK-c-Jun axis. 

PMID- 24751000
TI  - Gene expression profile of 5-fluorouracil metabolic enzymes in laryngeal cancer
      cell line: predictive parameters for response to 5-fluorouracil-based
      chemotherapy.
AB  - BACKGROUND: 5-fluorouracil (5-FU) is an antifolate chemotherapeutic that has
      become established in many therapeutic regimes, but sensitivity variations and
      development of resistance are common problems that limit the efficiency of the
      treatments. Inter-individual variations to 5-FU outcome have been attributed to
      different expression profiles of genes related to folate metabolism. METHODS: To
      elucidate the mechanisms of variations to 5-FU outcome, the authors investigated
      MTHFR, DHFR, TYMS and SLC19A1 folate genes expression for 5-FU response in
      laryngeal cancer cell line (Hep-2). Concentrations of 10, 50, and 100 ng/mL of 5
      FU chemotherapeutic were added separately in Hep-2 cell line for 24 hours at 37 
      degrees C. Cell sensibility was evaluated with fluorescein isothiocyanate (FITC)
      label Bcl-2 by flow cytometry. The real-time quantitative PCR (qPCR) technique
      was performed for quantification of gene expression using TaqMan((r)) Gene
      Expression Assay. ANOVA and Bonferroni's post hoc tests were utilized to
      statistical analysis. RESULTS: The numbers of viable Hep-2 cells with 10, 50, and
      100 ng/mL concentrations of 5-FU chemotherapy were 15.87, 28.3 and 68.9%,
      respectively. Statistical analysis showed significant association between control
      group and increased expression for TYMS gene in cells treated with 100 ng/mL/5-FU
      chemotherapy (P<0.05). CONCLUSIONS: The authors found association between the
      highest 5-FU dose chemotherapy and increased expression levels for TYMS folate
      gene in laryngeal cancer cell line. Although these experiments were performed in
      vitro, the results suggest that genetic factors are thought to play an important
      role in drug metabolism and may be useful for predicting treatment outcomes.

PMID- 24751001
TI  - NMDA receptors on the surface of cancer cells: target for chemotherapy?
AB  - The mammalian target of rapamycin (mTOR), a serine/threonine kinase, is a
      therapeutic target for many types of cancers. NMDA receptors regulate mTOR
      signalling activity; their inappropriate expression on several human cancer cell
      lines represents a potential therapeutic avenue to control dysregulated growth,
      division and invasiveness. Targeting these receptors with selective ligands
      (e.g., glycineB site ligands) may be a less toxic and more tolerable approach
      than administering compounds acting at the mTORC1 complex itself, such as
      rapamycin and its derivatives. Thus, testing glycineB site ligands in relevant in
      vitro and in vivo paradigms with established human cancer cells that express NMDA
      receptors on their surface could provide proofs of concept/principle that would
      encourage exploration of these and other "non-toxic" strategies. Interestingly,
      in some cancer models that express NMDA receptors on their surface, NMDA receptor
      antagonists, such as MK-801 (dizocilpine), were shown to possess anti
      proliferative and anti-invasive effects, which conflict with hypotheses about
      promoting NMDA receptor activation as a cancer chemotherapeutic strategy. Whether
      NMDA receptor activation or antagonism is associated with anti-proliferative and
      anti-invasive effects may reflect differences between cancer cell lines in terms
      of the proteins associated with the NMDA receptors on their cell surfaces, which,
      in turn, could lead to different "downstream" effects on cascades of
      intracellular phosphorylations. Irrespective of whether activation or antagonism
      is associated with anti-proliferative and anti-invasive effects for specific
      types of cancer, data are emerging that support exploration of targeting NMDA
      receptors expressed on the surface of cancer cells as a therapeutic strategy. 

PMID- 24751002
TI  - Expression of Lgr5, a marker of intestinal stem cells, in colorectal cancer and
      its clinicopathological significance.
AB  - Cancer stem cells (CSCs) have been the focus of intense investigations in cancer
      research although the cellular origin of CSCs has not been clearly determined.
      Lgr5 is a regulated target of Wnt/beta-catenin signaling, which was first
      identified as a marker of intestinal stem cells. However, the expression of Lgr5
      in human colorectal cancer (CRC) and its clinical clinicopathological
      significance in CRC patients as well as its correlation with Wnt/beta-catenin
      pathway are not fully explored. Localization and expression of Lgr5 in CRC
      tissues was performed by immunohistochemical staining. The correlation between
      its expression levels and clinicopathological features as well as clinical
      outcomes of patients was analysed. The quantitative expression levels of Lgr5 in
      various CRC cell lines were determined using real-time RT-PCR. The relationship
      between Lgr5 expression and Wnt/beta-catenin pathway in CRC was also
      investigated. Obviously elevated expression of Lgr5 was observed in CRC tissues,
      compared to the paired nontumor tissues. mRNA expression levels of Lgr5 was
      positively correlated with the expression of beta-catenin in CRC tissues. The
      expression of Lgr5 was various in different CRC cell lines. Low and high
      expression levels of Lgr5 were significantly correlated with clinicopathological
      features such as TNM stage, lymph node metastasis and vascular invasion of CRC
      patients. More importantly, Lgr5 expression in CRC tissues was also associated
      with tumor angiogenesis as well as clinical outcomes. Taken together, these
      results suggest that elevated Lgr5 expression might contribute to the development
      and progression of CRC, and it could also be used a potential unfavorable
      prognostic biomarker for CRC. A better understanding of molecule mechanisms and
      the relevance of potential value for Lgr5 in the progression of CRC will help to
      identify a novel therapeutic strategy for CRC patients. 

PMID- 24751003
TI  - Extraction of polysaccharides from a species of Chlorella.
AB  - The objective of this project was to devise a method to recover the total, water
      soluble cell-wall polysaccharides of Chlorella. It was found that substantial
      quantities of polysaccharides could be extracted after treatment of the cells
      with a mildly acidic solution of sodium chlorite (yield of recovered
      polysaccharide, 19-22%). Water-soluble (13-19% yield) and 2% NaOH-soluble (3-6%
      yield) fractions were obtained. A second treatment gave a total yield of water
      soluble polysaccharides of 24-25%, while reducing the amount of material soluble
      in 2% NaOH to 0.3%. Each polysaccharide fraction was composed of 6 different
      neutral sugars (rhamnose, arabinose, xylose, mannose, galactose, and glucose).
      There was evidence of the presence of uronic acid in all fractions. An alkaline
      hydrogen peroxide treatment of the cells resulted in a 19% yield of
      polysaccharides that were not further examined. 

PMID- 24751004
TI  - Fast and long-acting antibacterial properties of chitosan-Ag/polyvinylpyrrolidone
      nanocomposite films.
AB  - Infection associated with medical devices is one of the most frequent
      complications of modern medical biomaterials. Preparation of antibacterial films
      on the medical devices is a great challenge owing to bactericidal efficiency,
      long acting and biocompatibility. In this study, silver nanoparticles (Ag NPs)
      doped chitosan/polyvinylpyrrolidone (PVP) films were successfully prepared by dip
      coating method. The nanocomposite films with spherical Ag NPs (diameters in 10-50
      nm) were stable after being immersed in PBS for 35 days. Through regulating the
      concentration of AgNO3, the nanocomposite films showed good cell compatibility.
      The nanocomposite films could eliminate 100% Staphylococcus aureus (ATCC 6538)
      and Escherichia coli (ATCC 8739) in 5 min and had favorable long-acting
      antibacterial property. The increase of PVP amount obviously enhanced anti
      adhesion activity of the nanocomposite film. Such nanocomposite films can be
      expected to have good potential in biomaterials applications.

PMID- 24751006
TI  - Molecular, mesoscopic and microscopic structure evolution during amylase
      digestion of maize starch granules.
AB  - Cereal starch granules with high (>50%) amylose content are a promising source of
      nutritionally desirable resistant starch, i.e. starch that escapes digestion in
      the small intestine, but the structural features responsible are not fully
      understood. We report the effects of partial enzyme digestion of maize starch
      granules on amylopectin branch length profiles, double and single helix contents,
      gelatinisation properties, crystallinity and lamellar periodicity. Comparing
      results for three maize starches (27, 57, and 84% amylose) that differ in both
      structural features and amylase-sensitivity allows conclusions to be drawn
      concerning the rate-determining features operating under the digestion conditions
      used. All starches are found to be digested by a side-by-side mechanism in which
      there is no major preference during enzyme attack for amylopectin branch lengths,
      helix form, crystallinity or lamellar organisation. We conclude that the major
      factor controlling enzyme susceptibility is granule architecture, with shorter
      length scales not playing a major role as inferred from the largely invariant
      nature of numerous structural measures during the digestion process (XRD, NMR,
      SAXS, DSC, FACE). Results are consistent with digestion rates being controlled by
      restricted diffusion of enzymes within densely packed granular structures, with
      an effective surface area for enzyme attack determined by external dimensions (57
      or 84% amylose - relatively slow) or internal channels and pores (27% amylose -
      relatively fast). Although the process of granule digestion is to a first
      approximation non-discriminatory with respect to structure at molecular and
      mesoscopic length scales, secondary effects noted include (i) partial
      crystallisation of V-type helices during digestion of 27% amylose starch, (ii)
      preferential hydrolysis of long amylopectin branches during the early stage
      hydrolysis of 27% and 57% but not 84% amylose starches, linked with disruption of
      lamellar repeating structure and (iii) partial B-type recrystallisation after
      prolonged enzyme incubation for 57% and 84% amylose starches but not 27% amylose
      starch. 

PMID- 24751005
TI  - Preparation and characterization of cationic curcumin nanoparticles for
      improvement of cellular uptake.
AB  - In the present paper, cationic nanoparticles of curcumin, chitosan and poly(E
      caprolactone) were developed by a simple nano-precipitation method. The developed
      curcumin loaded chitosan/poly(E-caprolactone) (chitosan/PCL) nanoparticle showed
      almost spherical shape and its diameter was varied between 220 nm and 360 nm and
      zeta potential was varied between +30 mV and 0 mV as a function with pH value.
      The encapsulation of curcumin into nanoparticles was confirmed by fluorescence
      spectral analysis. In vitro release study showed the sustained release behavior
      of curcumin from nanoparticles during the period of 5 days study. In vitro
      cytotoxicity test revealed the drug concentration dependent on the cell viability
      against Hela cells and OCM-1 cells after 48 h co-incubation. Furthermore, in
      vitro cell uptake study revealed that the cell uptake of curcumin was greatly
      enhanced by encapsulated curcumin into cationic chitosan/PCL nanoparticles.
      Therefore, the developed cationic chitosan/PCL nanoparticles might be a promising
      candidate for curcumin delivery to cancer cells.

PMID- 24751007
TI  - Compatible blends of thermoplastic starch and hydrolyzed ethylene-vinyl acetate
      copolymers.
AB  - Ethylene-vinyl acetate copolymer (EVA) with 19% of vinyl acetate and its
      derivatives modified by hydrolysis of 50 and 100% of the initial vinyl acetate
      groups were used to produce blends with thermoplastic starch (TPS) plasticized
      with 30 wt% glycerol. The blends were characterized by Fourier transform infrared
      spectroscopy, scanning electron microscopy, X-ray diffraction, water absorption,
      stress-strain mechanical tests, dynamic mechanical analysis and thermogravimetric
      analysis. In contrast to the blends with unmodified EVA, those made with
      hydrolyzed EVA were compatible, as demonstrated by the brittle fracture surface
      analysis and the results of thermal and mechanical tests. The mechanical
      characteristics and water absorption of the TPS were improved even with a small
      addition (2.5 wt%) of hydrolyzed EVA. The glass transition temperature rose with
      the degree of hydrolysis of EVA by 40 and 50 degrees , for the EVA with 50 and
      100% hydrolysis, respectively. The addition of hydrolyzed EVA proved to be an
      interesting approach to improving TPS properties, even when very small quantities
      were used, such as 2.5 wt%.

PMID- 24751008
TI  - Combined HILIC-ELSD/ESI-MS(n) enables the separation, identification and
      quantification of sugar beet pectin derived oligomers.
AB  - The combined action of endo-polygalacturonase (endo-PGII), pectin lyase (PL),
      pectin methyl esterase (fungal PME) and RG-I degrading enzymes enabled the
      extended degradation of methylesterified and acetylated sugar beet pectins
      (SBPs). The released oligomers were separated, identified and quantified using
      hydrophilic interaction liquid chromatography (HILIC) with online electrospray
      ionization ion trap mass spectrometry (ESI-IT-MS(n)) and evaporative light
      scattering detection (ELSD). By MS(n), the structures of galacturonic acid (GalA)
      oligomers having an acetyl group in the O-2 and/or O-3 positions eluting from the
      HILIC column were elucidated. The presence of methylesterified and/or acetylated
      galacturonic acid units within an oligomer reduced the interaction with the HILIC
      column significantly compared to the unsubstituted GalA oligomers. The HILIC
      column enables a good separation of most oligomers present in the digest. The use
      of ELSD to quantify oligogalacturonides was validated using pure GalA standards
      and the signal was found to be independent of the chemical structure of the
      oligomer being detected. The combination of chromatographic and enzymatic
      strategies enables to distinguish SBPs having different methylesters and acetyl
      group distribution. 

PMID- 24751009
TI  - Structural data on a bacterial exopolysaccharide produced by a deep-sea
      Alteromonas macleodii strain.
AB  - Some marine bacteria collected around deep-sea hydrothermal vents are able to
      produce, in laboratory conditions, complex and innovative exopolysaccharides. In
      a previous study, the mesophilic strain Alteromonas macleodii subsp. fijiensis
      biovar deepsane was collected on the East Pacific Rise at 2600 m depth. It was
      isolated from a polychaete annelid Alvinella pompejana and is able to synthesise
      and excrete the exopolysaccharide deepsane. Biological activities have been
      screened and some protective properties have been established. Deepsane is
      commercially available in cosmetics under the name of Abyssine((r)) for soothing
      and reducing irritation of sensitive skin against chemical, mechanical and UVB
      aggression. This study presents structural data for this original and complex
      bacterial exopolysaccharide and highlights some structural similarities with
      other known EPS produced by marine Alteromonas strains.

PMID- 24751010
TI  - Structure of oligosaccharide F21 derived from exopolysaccharide WL-26 produced by
      Sphingomonas sp. ATCC 31555.
AB  - Mild hydrolysis of Sphingomonas sp. ATCC 31555 polysaccharide WL-26 afforded a
      new oligosaccharide, F21. Structural resolution based on sugar and methylation
      analyses as well as NMR data revealed the oligosaccharide to have the following
      structure: [Formula, see text:].

PMID- 24751011
TI  - Characterization and antitumor activities of the water-soluble polysaccharide
      from Rhizoma Arisaematis.
AB  - A water soluble polysaccharide (RAP-W1) was purified from Rhizoma Arisaematis and
      its antitumor activity was evaluated in BALB/c mice bearing human breast cancer
      MCF-7. RAP-W1 had the following physicochemical properties: total carbohydrate
      content (95.9%); no protein; molecular weight (~57 kDA); monosaccharides
      composition
      (rhamnose:fucose:arabinose:mannose:galactose:glucose=0.4:0.5:0.3:0.6:0.9:5.3).
      After 14 days' treatment to tumor-bearing mice, RAP-W1 could significantly
      inhibit the growth of tumor transplanted in mice and increase the body weight and
      the spleen index. Moreover, RAP-W1 could significantly stimulate Con A- or LPS
      induced splenocyte proliferation in tumor-bearing mice, as well as enhance the
      CTL activity. The level of Th1 cytokines (INF-gamma and IL-2) in the serum of
      tumor-bearing mice was increased by RAP-W1 treatment, whereas the Th2 cytokine
      (IL-10) secretion displayed a dramatic reduction. All the data implied that RAP
      W1 can activate T cells by up-regulating Th1/Th2 cytokine ratio, which might
      partially cause the inhibition of tumor growth.

PMID- 24751012
TI  - Products from microwave and ultrasonic wave assisted acid hydrolysis of chitin.
AB  - Hydrolysis of alpha-chitin in concentrated hydrochloric acid under elevated
      temperature is a general preparation of a nutrapharmaceutical glucosamine
      hydrochloride (GlcN.HCl). In this study, the microwave and ultrasonic wave
      assisted acid hydrolysis of shrimp shell alpha-chitin are investigated with an
      aim to improve the reaction rate and selectivity. Microwave heating shortens the
      hydrolysis time from 120 min in the conventional heating process to 12 min to
      afford GlcN.HCl in 57% yield. Sonication can be used to assist chitin dissolution
      in 38% HCl prior to the hydrolysis at 120  degrees C for 120 min to produce
      GlcN.HCl in 62% yield. The selective hydrolysis of glycosidic bond of chitin is
      achievable at 30  degrees C for 4 h to give N-acetyl glucosamine (GlcNAc) in 37%
      yield.

PMID- 24751013
TI  - Aluminum carboxymethyl cellulose-rice bran microcapsules: enhancing survival of
      Lactobacillus reuteri KUB-AC5.
AB  - This research aimed to enhance the survival of Lactobacillus reuteri KUB-AC5 from
      heat conditioning by using microencapsulation with aluminum carboxymethyl
      cellulose-rice bran (AlCMC-RB) composites of different weight ratios of 1:0, 1:1,
      and 1:1.5. The cell/polymer suspension was crosslinked with aluminum chloride at
      different agitation speeds of 1200, 1500, and 2100 rpm. The AlCMC microcapsules
      had significantly higher encapsulation efficiency, but lower microcapsule yield
      than the AlCMC-RB microcapsules (p<=0.05). Scanning electron microscopy revealed
      the complexation between AlCMC and RB. Fourier transform infrared spectroscopy
      showed hydrogen bondings between AlCMC, RB, and cells. The AlCMC-RB microcapsules
      had significantly lower aluminum ion and moisture contents than the AlCMC ones.
      After heat exposure, the viability of non-encapsulated and microencapsulated
      cells in the AlCMC matrix dramatically declined, while that of microencapsulated
      cells in the AlCMC-RB matrix was about 8 log CFU/g. The results showed the
      promising potential of the AlCMC-RB composite microcapsules for the protection of
      probiotics against heat.

PMID- 24751014
TI  - Oxidation of crosslinked chitosan-epichlorohydrine film and its application with
      TiO2 for phenol removal.
AB  - Photocatalytic oxidation of crosslinked chitosan-epichlorohydrin (CS-ECH) film
      was successfully achieved via an immobilized TiO2/CS-ECH photocatalyst system on
      a glass plate. Oxidation process of CS-ECH film was carried out by irradiating
      the system with a 45-W fluorescent lamp for 10h in ultra-pure water. The results
      indicate the formation of carbonyl functional groups and partial elimination of
      amine groups in the molecular structure of the oxidized CS-ECH film. This
      oxidized CS-ECH film has different optical properties, ionic conductivity, degree
      of transparency, swelling index and chemical stability than the fresh CS-ECH
      film. In the environmental applications, the TiO2/oxidized-CS-ECH photocatalyst
      system can have photodegradation and faster mineralization rate of phenol than
      both fresh TiO2/CS-ECH and TiO2/oxidized-CS photocatalyst systems. This simple
      photocatalyst system, therefore can be considered as an environmental friendly
      method to oxidize synthetic biopolymer and to improve the photocatalytic
      efficiency of TiO2 to treat wastewater. 

PMID- 24751015
TI  - Isolation and structural characterization of the polysaccharide LRGP1 from Lycium
      ruthenicum.
AB  - A novel water-soluble glycoconjugate, designated as Lycium ruthenicum
      glycoconjugate polysaccharide 1 (LRGP1), was isolated from the fruits of Lycium
      ruthenicum Murr. The crude polysaccharide was obtained by hot water extraction
      and purified by ion-exchange and gelfiltration chromatography. Its molecular
      weight was 56.2 kDa determined by HPGPC (high performance gel permeation
      chromatography). Monosaccharide composition analysis revealed that it was
      composed of rhamnose, arabinose, xylose, mannose, glucose, and galactose in a
      molar ratio of 0.65:10.71:0.33:0.67:1:10.41. The existence of O-type carbohydrate
      peptide linkage in LRGP1 was demonstrated by beta-elimination reaction. On the
      basis of monosaccharide composition, partial acid hydrolysis, methylation
      analysis and ESI-MS analysis, LRGP1 was characterized as a branched
      polysaccharide rich in arabinose and galactose with a backbone composed of (1->3)
      linked Gal. The branches were composed of (1->5)-linked Ara, (1->2)-linked Ara,
      (1->6)-linked Gal, (1->3)-linked Gal, (1->4)-linked Gal and (1->2,4)-linked Rha.
      Arabinose, xylose, mannose, and glucose were located at the terminal of the
      branches.

PMID- 24751016
TI  - Wood chemistry and density: an analog for response to the change of carbon
      sequestration in mangroves.
AB  - This study aimed to resolve the variations of physical and chemical properties of
      wood records measured in different mangroves with their annual carbon
      sequestration. The methods of investigation used were to examine growth rate by
      monitoring breast height diameter, wood chemistry and density, FTIR spectroscopy
      and thermogravimetry. Carbon sequestration rate showing an increase with density
      varied between 0.088 and 0.171 MUg C kg(-1) AGB s(-1), and Avicennia marina
      showed the maximum value and Bruguiera gymnorrhiza, the minimum. The changes in
      FTIR bands at 4000-2500 cm(-1) and 1700-800 cm(-1) were correlated to the
      variations in cellulose in mangrove woods and lignin to cellulose ratio ranged
      between 0.21 and 1.75. Thermal analyses of mangrove wood suggested that the fuel
      value index (985-3922) exhibited an increase with the decrease in maximum
      decomposition temperature and density. The seasonal variation of temperature and
      CO2 were likely to affect chemical properties through changes in wood density.

PMID- 24751017
TI  - Alginate-based composite sponge containing silver nanoparticles synthesized in
      situ.
AB  - Silver-based biomaterials have been developed in a variety of bactericidal
      applications, especially for wound dressings. In this study, silver nanoparticles
      (AgNPs) were synthesized in a sodium alginate solution and then the composite
      sponge containing AgNPs was prepared from the nanocolloid solution. The alginate
      stabilized AgNPs had the mean negative zeta potential of -52.5mV, suggesting that
      the surface charge prevents the nanoparticles from aggregating through
      electrostatic repulsion. The alginate-AgNPs composite sponge had a highly
      enhanced antimicrobial activity compared to the alginate sponge. In spite of
      excellent cytocompatibility of the alginate sponge, the viability of the cell
      treated with the alginate-AgNPs composite sponge extract decreased to 86% of the
      control. The amount of proinflammatory cytokines released from macrophages
      treated with the alginate-AgNPs composite sponge was reduced. For the preparation
      of AgNPs-embedded composites, alginate can be a potential candidate stabilizing
      AgNPs and providing synergistic antimicrobial and antiinflammatory activities
      with AgNPs. 

PMID- 24751018
TI  - Thin stillage supplementation greatly enhances bacterial cellulose production by
      Gluconacetobacter xylinus.
AB  - Thin stillage (TS), a wastewater from rice wine distillery can well sustain the
      growth of Gluconacetobacter xylinus for production of bacterial cellulose (BC).
      When used as a supplement to the traditional BC production medium (Hestrin and
      Schramm medium), the enhancement of BC production increased with the amount of TS
      supplemented in a static culture of G. xylinus. When TS was employed to replace
      distilled water for preparing HS medium (100%TS-HS medium), the BC production in
      this 100%TS-HS medium was enhanced 2.5-fold to a concentration of 10.38 g/l with
      sugar to BC conversion yield of 57% after 7 days cultivation. The cost-free TS as
      a supplement in BC production medium not only can greatly enhance the BC
      production, but also can effectively dispose the nuisance wastewater of rice wine
      distillery.

PMID- 24751019
TI  - Synthesis and characterization of selenium-chondroitin sulfate nanoparticles.
AB  - A novel selenium-chondroitin sulfate (SeCS) was synthesized by ultrasonic and
      dialysis method. With characterization by FTIR, XRD and TEM, the SeCS was found
      to form nanoparticles in distilled water through a self-aggregation progress. The
      SeCS nanoparticles had sizes between 30 and 200 nm with selenium entrapment
      efficiency of about 10.1%. The anti-toxin capacity of SeCS nanoparticles was
      demonstrated through MTT and apoptosis assays in vitro. Results indicated that
      the SeCS was less cytotoxic to chondrocytes than sodium selenite. In particular,
      the SeCS could obviously alleviate chondrocyte apoptosis induced by T-2 toxin
      compared to chondroitin sulfate. These results thus represent an advanced
      understanding of the properties of SeCS nanoparticles and demonstrate their
      exciting potential applications in therapy of Kashin-Beck disease (KBD) and
      osteoarthritis.

PMID- 24751020
TI  - In vitro and in vivo theophylline release from cellulose/chondroitin sulfate
      hydrogels.
AB  - In vitro and in vivo release of the theophylline, loaded in mixed polysaccharidic
      cellulose/chondroitin sulfate (C/CS) hydrogels has been evaluated. The C/CS
      hydrogels in various mixing ratios obtained by a crosslinking technique were
      supplementary characterized by swelling studies in a pH 2.2 acidic solution at 37
      degrees C, simulating the gastrointestinal medium, as in vivo theophylline
      delivery was done by oral administration. The hydrogels loading degree with
      theophylline was evaluated by near infrared chemical imaging (NIR-CI) technique
      and confirmed also by FT-IR spectroscopy. Based on PLS-DA (partial least squares
      discriminate analysis) prediction, the drug loading was found up to 92.5%. The in
      vitro release profiles of theophylline from C/CS hydrogels showed that an
      increase of chondroitin sulfate leads to a decreased theophylline percent
      released, increased half release time and time to reach maximum percent released.
      During in vivo test, the raw theophylline was rapidly, absorbed, distributed, and
      eliminated. Comparatively with raw drug administration, the t1/2 and AUC0-72
      value were 4 times higher for theophylline loaded into 50/50 C/CS hydrogel. A
      good in vitro-in vivo correlation was found. A retarded release, controlled by CS
      content can be achieved by using mixed hydrogels as carriers.

PMID- 24751021
TI  - Characterization of fungal sulfated polysaccharides and their synergistic
      anticancer effects with doxorubicin.
AB  - Sulfated polysaccharides (SPSs) from two edible fungal species, including two
      strains of Antrodia cinnamomea and Poria cocos, were isolated. Fucose,
      glucosamine, galactose, glucose, and mannose were the major sugars in the SPSs,
      and these SPSs had a high sulfate content. The area percentage of low-molecular
      weight SPSs (1-100 kDa) covered almost half of the SPS mixture of the A.
      cinnamomea strains. In contrast, high-molecular-weight SPSs (>1000 kDa) of P.
      cocos covered a large proportion of the area at 30.06%. SPSs from A. cinnamomea
      B86 showed stronger inhibition of endothelial cell (EC) tube formation in an in
      vitro assay of angiogenesis, than did A. cinnamomea 35396 or P. cocos. The degree
      of sulfation paralleled their antiangiogenic activity. When tumor cells were
      concurrently exposed to doxorubicin (DOX) and fungal SPSs, SPSs synergistically
      increased the cytotoxicity of DOX to different degree up to 50-fold. Fungal SPSs
      may offer new applications for combinational-therapy drugs.

PMID- 24751022
TI  - Devitrification of the amorphous fractions of starch during gelatinisation.
AB  - Gelatinisation of waxy maize starch (WMS) in excess glycerol was investigated by
      a temperature modulated DSC in quasi-isothermal and non-isothermal mode. By using
      the measured specific heat capacities (cp) at different stages of gelatinisation
      and the hypothetical enthalpy of melting for 100% crystalline amylopectin, a
      method was developed to reveal the amorphous fraction which remains glassy in the
      presence of excess glycerol what can be called "rigid amorphous". It was
      suggested that the amorphous part of starch was plasticised at around 40  degrees
      C whereas, rigid amorphous fraction underwent a second stage glass transition
      which showed itself by an increase in cp under the gelatinisation endotherm. It
      was also shown that holding WMS in excess glycerol at 100  degrees C (10  degrees
      C above the gelatinisation onset temperature) for 10 days was not enough to
      gelatinise the whole WMS implicating that the most stable crystals did not melt
      before the required threshold temperature was reached.

PMID- 24751023
TI  - Electrical insulated paper from cotton linter.
AB  - Insulated paper had been prepared from cotton linter containing certain
      additives. Strength properties had been studied for all paper prepared from
      cotton linter, before and after impregnating in the linseed oil. Also, the
      dielectric constant (epsilon) and AC electrical conductivity with frequencies
      over the range (100 kHz to 3 MHz) and at different temperatures were studied.
      Blended cotton linter with glass fiber or polyester fiber increased the
      dielectric constant. Since the glass fibers lowered the power factor from 0.63 to
      0.28% and enhanced dielectric constant. The addition of hydrophilic fibers such
      as rayon or polyester fiber can be made paper of low porosity, low density and
      high dielectric resistance. Also, the addition of lead sulphate improved
      dielectric constant of paper since it has dielectric coefficient >20. The
      dielectric constant in sample which dipped in oil is higher than the sample
      without oil.

PMID- 24751024
TI  - Coupling lipophilization and amylose complexation to encapsulate chlorogenic
      acid.
AB  - Chlorogenic acid (5-caffeoylquinic acid) is a hydrophilic phenolic compound with
      antioxidant properties. Because of its high polarity, these properties may be
      altered when formulated in oil-based food. There is therefore an interest in
      trying to protect the natural antioxidant by molecular encapsulation. Amylose,
      the linear fraction of starch with essentially alpha(1-4) linkages, is well known
      for its ability to form semi-crystalline complexes with a variety of small
      ligands. Monoacyl lipids, as well as smaller ligands such as alcohols or flavor
      compounds, are able to induce the formation of left-handed amylose single
      helices. In contrast, chlorogenic acid is a bulky molecule whose topology
      requires the amylose helix to be distorted, which could prevent amylose
      complexation. An innovative strategy has been developed to overcome this problem
      by grafting an aliphatic chain onto chlorogenic acid then trapping this chain in
      the helical cavity. The lipophilization reaction was used to obtain a palmitoyl
      chlorogenic acid derivative and the amylose-palmitoyl chlorogenic acid assemblies
      were studied by X-ray diffraction, differential scanning calorimetry and NMR to
      elucidate the interaction. The results showed that such interactions between
      amylose and palmitoyl chlorogenic acid are effective. 

PMID- 24751025
TI  - Effect of organic acids as additives on the performance of thermoplastic
      starch/polyester blown films.
AB  - The influence of citric acid (CA), malic acid (MA) and tartaric acid (TA) in
      starch/poly (butylene adipate co-terephthalate) blown films was evaluated by
      examining the barrier, structural and mechanical properties of the films. These
      properties were analysed in different relative humidities. Greater concentrations
      of TA and CA (1.5 wt%) produced films with improved tensile strength (6.8+/-0.3
      and 6.7+/-0.3 MPa, respectively), reduced water vapour permeability and a more
      homogeneous structure. The compatibilising effect of MA was less efficient, as
      shown in the scanning electron microscopy (SEM) images. Changes in the relative
      humidity (RH) affected the elongation of the films, which reached values of 5.7+/
      0.5 at 33% RH and increased to 312.4+/-89.5% at 53% RH. The FT-IR spectra showed
      no additional reactions caused by the incorporation of the additives, and the
      observed results are attributed to the esterification reactions and/or hydrolysis
      of the starch, producing films with interesting properties. This process
      represents an alternative to the use of non-biodegradable materials.

PMID- 24751026
TI  - Superabsorbent nanocomposite (alginate-g-PAMPS/MMT): synthesis, characterization
      and swelling behavior.
AB  - A superabsorbent composite (alginate-g-PAMPS/MMT) was prepared by graft
      copolymerization from alginate, 2-acrylamido-2-methyl-1-propanesulfonic acid
      (AMPS) and Na+ montmorillonite (MMT) in an inert atmosphere. Effects of
      polymerization variables on water absorbency, including the content of Na+
      montmorillonite, sodium alginate, N,N'-methylenebisacrylamide and AMPS, were
      studied. The introduced montmorillonite formed a loose and porous surface and
      improved the water absorbency of the alginate-g-PAMPS/MMT superabsorbent
      composite. Swelling behaviors of the superabsorbent composites in various
      cationic salt solutions (NaCl, CaCl2 and FeCl3) and anionic salt solutions (NaCl
      and Na2SO4) were also systematically investigated. The superabsorbent composite
      was further characterized using Fourier transform infrared spectroscopy (FTIR),
      rheology, thermogravimetric analysis (TGA), X-ray diffraction (XRD) and scanning
      electron microscopy (SEM) taking alginate-g-PAMPS as a reference. 

PMID- 24751027
TI  - Potential antidiabetic activity of extracellular polysaccharides in submerged
      fermentation culture of Coriolus versicolor LH1.
AB  - The separation and purification of extracellular polysaccharides from Coriolus
      versicolor LH1 were investigated along with their alpha-glucosidase inhibition
      properties. Three polysaccharide fractions (ePS-F2-1, ePS-F3-1, and ePS-F4-1)
      were separated from the culture medium of LH1 using a DEAE anion-exchange column
      and a SephadexTM G-50 gel filtration column. Their chemical compositions was
      determined. On the basis of an alpha-glucosidase inhibition assay, the enzyme
      inhibition activities of ePS-F2-1, ePS-F3-1, and ePS-F4-1 were investigated.
      Among these, ePS-F4-1 had the highest enzyme inhibition effects on alpha
      glucosidase. According to the results of the chemical component analysis, ePS-F3
      1 and ePS-F4-1 are the polysaccharides which are combined with triterpenoides,
      and ePS-F2-1 is complexed with proteins and triterpenoides. 

PMID- 24751028
TI  - Fabrication of electrospun biocomposites comprising polycaprolactone/fucoidan for
      tissue regeneration.
AB  - In this study, we designed a new biocomposite comprising electrospun
      polycaprolactone (PCL)/fucoidan, in which the fucoidan has various beneficial
      biological functions, including anticoagulant, antiviral, and immunomodulatory
      activity. To obtain the composite scaffolds, a mixture of PCL and fucoidan was
      electrospun using various compositions (1, 2, 3, and 10 wt.%) of fucoidan
      powders. The resultant electrospun composites exhibited improved tensile modulus
      and strength for limited weight fractions (<10 wt.%) of fucoidan when compared
      with the pure PCL fiber mats. In addition, the biocomposites showed dramatic
      hydrophilic properties at >3 wt.% of fucoidan in the PCL/fucoidan. The
      biocompatibility of the electrospun mats was examined in vitro using osteoblast
      like cells (MG63). Total protein content, alkaline phosphatase activity, and
      calcium mineralization were assessed. Scanning electron microscopic images showed
      that the cells were distributed more widely and were agglomerated on PCL/fucoidan
      mats compared with pure PCL mats. In addition, total protein content, alkaline
      phosphatase activity, and calcium mineralization were higher with PCL/fucoidan
      mats than with pure PCL mats. These observations suggest that fucoidan
      supplemented biocomposites would make excellent materials for tissue-engineering
      applications.

PMID- 24751029
TI  - Bioconjugation of quantum-dots with chitosan and N,N,N-trimethyl chitosan.
AB  - Novel carbohydrate-based hybrids combining chitosan and chemically modified
      chitosan with CdS inorganic nanoparticles were designed and prepared via aqueous
      route at room temperature. N,N,N-trimethylchitosan (TM-chitosan) was synthesized
      aiming at substantially improving the water solubility of chitosan for producing
      stable colloidal systems. UV-vis spectroscopy, photoluminescence spectroscopy,
      Nuclear magnetic resonance spectroscopy, Raman spectroscopy, and Fourier
      transform infrared spectroscopy were used to characterize the synthesis and the
      relative stability of biopolymer-capped CdS nanocrystals. The results have
      clearly indicated that chitosan and chitosan-derivative (TM-chitosan) were
      remarkably effective on nucleating and stabilizing CdS nanoparticles in aqueous
      suspensions. In addition, the CdS nanocrystals were produced in the so-called
      "quantum-size confinement regime", with the calculated average size below 3.5 nm
      and fluorescent activity in the visible range of the spectra. Therefore, a new
      single-step process was developed for the bioconjugation of quantum dots with
      water soluble chemically functionalized carbohydrates at room temperature for
      potential biomedical applications.

PMID- 24751030
TI  - alpha-Chitin nanofibrils improve inflammatory and fibrosis responses in
      inflammatory bowel disease mice model.
AB  - We evaluated the anti-inflammatory and anti-fibrosis effects of alpha-chitin
      nanofibrils in a mouse model of dextran sulfate sodium (DSS)-induced acute
      ulcerative colitis (UC). alpha-Chitin nanofibrils decreased positive areas of
      nuclear factor-kappaB staining in the colon tissue (7.2+/-0.5%/fields in the
      alpha-chitin nanofibrils group vs. 10.7+/-0.9%/fields in the control group;
      p<0.05). alpha-Chitin nanofibrils also decreased serum monocyte chemotactic
      protein-1 concentration in DSS-induced acute UC (24.1+/-7.8 pg/ml in the alpha
      chitin nanofibrils group vs. 53.5+/-3.1 pg/ml in the control group; p<0.05).
      Moreover, alpha-chitin nanofibrils suppressed the increased positive areas of
      Masson's trichrome staining in colon tissue (6.8+/-0.6%/fields in the alpha
      chitin nanofibrils group vs. 10.1+/-0.7%/fields in the control group; p<0.05). On
      the other hand, alpha-chitin powder suspension did not show these effects in DSS
      induced acute UC mice model. Our results indicated that alpha-chitin nanofibrils
      have the anti-inflammatory effect via suppressing NF-kappaB activation and the
      anti-fibrosis effects in DSS-induced acute UC mice model.

PMID- 24751031
TI  - The grafting of acrylic acid onto biosorbents: effect of plant components and
      initiator concentration.
AB  - Acrylic acid was grafted onto raw and Fenton's reagent treated pine cone using
      KMnO4 as initiator to determine the effect of plant organic components on
      grafting process. Concentration of the KMnO4 was varied between 0.0005 and 0.0200
      mol/dm(3) and progress of the initiation process monitored using ORP and change
      in hydrogen ion concentration (DeltaH(+)). The optimum ratio for Fenton's
      modification was Fe(2+)/H2O2=1/50 which corresponds to the highest leaching of
      plant components and having the least bulk density, ORP and DeltaH(+). It was
      observed that increasing KMnO4 concentration, reduced the MnO2 deposited on the
      pine surface, increased Mn(3+) production in bulk solution while reducing
      grafting efficiency but increasing homopolymer formation. Radical formation on
      the raw pine cone was found to be lower as seen from the lower ORP and DeltaH(+)
      values observed at similar grafting conditions. Plant organic components was
      observed to affect the grafting efficiency and monomer conversion as observed
      from the weight increase, surface charge and FTIR analysis of the acrylic acid
      grafted Fenton's reagent treated pine and the raw pine. Optimum dye removal did
      not correspond to highest grafting efficiency.

PMID- 24751032
TI  - Bio-based nanocomposites obtained through covalent linkage between chitosan and
      cellulose nanocrystals.
AB  - Bio-based nanocomposites were obtained through covalent linkage between cellulose
      nanocrystals (CNCs) and the natural polymer chitosan (CH). The CNCs were first
      functionalized with methyl adipoyl chloride (MAC) and the reactive end groups on
      the surface of the CNCs were reacted with the amino groups of the CH biopolymer
      in an aqueous medium. The functionalized CNCs and the resulting nanocomposites
      were characterized using FTIR, TEM, XRD, and elemental analyses. Characterization
      of the functionalized CNCs showed that up to 8% of the hydroxyl groups in the
      nanocrystals were substituted by the MAC residue. The covalent linkage between
      the CNCs and CH was confirmed by FTIR spectroscopy. The nanocomposites
      demonstrated a significant improvement in the mechanical performance and a
      considerable decrease in the hydrophilicity relative to the neat chitosan. The
      approach used in this work can be extended to other natural polymers. 

PMID- 24751033
TI  - A kinetic model for oxidative degradation of bagasse pulp fiber by sodium
      periodate.
AB  - In this paper, some key parameters, such as the system pH, the periodate
      concentration, and the reaction temperature, on the influence of the bagasse
      fiber degradation were studied based on the oxygenant of periodate. And the
      feasible reaction mechanism was also discussed through the FTIR characterization
      for bagasse fiber before and after the oxidizing reaction. As the results shown,
      the crystallinity of bagasse fiber decreased with the oxidation level increasing.
      It was interesting that the aldehyde content of the reaction system rose
      gradually along with cellulose degradation. Based on this result, the selective
      oxidation kinetics was constructed by introducing of variable factor R (the ratio
      of aldehyde content to the degradation of cellulose fiber), and the results shown
      that there was a better correlation between the dynamic model and the
      experimental data, so the oxidation degree of bagasse fiber oxidized by periodate
      can be quantitative evaluated based on this model. 

PMID- 24751034
TI  - Effect of enzymatic depolymerization on physicochemical and rheological
      properties of guar gum.
AB  - Depolymerization of guar gum using enzymatic hydrolysis was performed to obtain
      depolymerized guar gum having functional application as soluble dietary fiber.
      Enzymatic hydrolysis of guar gum significantly affected the physicochemical and
      rheological characteristics of guar gum. The depolymerized guar gum showed a
      significant increase in crystallinity index from 3.86% to 13.2% and flow behavior
      index from 0.31 to 1.7 as compared to native guar gum. Remarkable decrease in
      intrinsic viscosity and consistency index was also observed from 9 to 0.28 and
      4.04 to 0.07, respectively. Results revealed that enzymatic hydrolysis of guar
      gum resulted in a polysaccharide with low degree of polymerization, viscosity and
      consistency which could make it useful for incorporation in food products as
      dietary fiber without affecting the rheology, consistency and texture of the
      products. 

PMID- 24751035
TI  - Mass spectrometry characterization of an Aloe vera mannan presenting
      immunostimulatory activity.
AB  - Aloe vera acemannan is a polysaccharide composed by a backbone of beta-(1->4)
      linked D-mannose residues interspersed by few glucose residues, acetylated in O
      2, O-3, and O-6 containing side chains constituted by O-6-linked single alpha-D
      galactose and alpha-L-arabinose residues. This structural features are rather
      similar to mannans from other sources, namely coffee and locust bean gum.
      However, Aloe vera acemannan and coffee mannans present immunostimulatory
      activity but locust bean gum does not. In order to know more about the structural
      features of a commercial preparation of Aloe vera presenting comparable
      immunostimulatory activity to that observed for coffee mannans, this preparation
      was submitted to sugar and methylation analysis. To gain further insight to the
      structural details of the mannans, focusing in the study of acetylation pattern,
      a specific hydrolysis with an endo-beta-(1->4)-D-mannanase was performed and the
      resulting oligosaccharides (OS) were fractionated by size exclusion
      chromatography and characterized by ESI-MS, ESI-MS/MS and MALDI-MS. The majority
      of the OS obtained for acemannan had a ratio of two acetyl groups per sugar
      residue. The observation of OS highly acetylated as well as non-acetylated OS,
      allowed to infer a non-homogeneous distribution of the acetyl groups. Also, it
      was observed OS presenting fully acetylated arabinose residues. The occurrence of
      a high abundance of acetylated residues shows that this polysaccharide contains
      odd acetylation content. These unusual features are reinforced by the presence of
      acetylated side chains, only previously observed in chemically acetylated mannans
      with immunostimulatory activity prepared from coffee residue. The comparison with
      other galactomannans allowed to infer that lower branching, shorter chains, and
      higher acetylation seems to promote the immunostimulatory activity attributed to
      these polysaccharides.

PMID- 24751036
TI  - Solution properties of capsular polysaccharides from Streptococcus pneumoniae.
AB  - Capsular polysaccharides from ten different serotypes of Streptococcus pneumoniae
      have been studied with regards their hydrodynamic properties in solution, namely
      their sedimentation coefficient and molar mass distributions, solution
      conformations and flexibilities (persistence lengths Lp), important properties
      for the construction of polysaccharide and glycoconjugate vaccines. Sedimentation
      and molar mass distributions (obtained by sedimentation velocity and equilibrium
      analysis in the analytical ultracentrifuge supported by size exclusion
      chromatography coupled to multi-angle light scattering measurements) were
      generally unimodal, with weight (mass) average molar masses ranging from
      100*10(3) to 1300*10(3) g/mol. Estimates of chain flexibilities from three
      different procedures applied to intrinsic viscosity, sedimentation coefficient
      and molar mass data, showed that the polysaccharides from all the serotypes
      studied had semi-flexible structures in solution with persistence lengths in the
      range from ~4 to 9 nm.

PMID- 24751037
TI  - Structural characterization of an acidic polysaccharide from Dalbergia sissoo
      Roxb. leaves.
AB  - The composition and structure of an acidic polysaccharide from the leaves of
      Dalbergia sissoo was studied using hydrolytic, methylation, (1)H/(13)C
      heteronuclear multiple quantum coherence (HMQC) and periodate oxidation
      experiments. The repeating unit of sissoo polysaccharide was found to be composed
      of alpha-L-rhamnose, beta-D-glucuronic acid, beta-D-galactose and beta-D-glucose
      in the molar ratio of 1.00:1.00:2.00:2.33, respectively. The structure of
      polysaccharide was mainly composed of (1->2), (1->3), (1->4) linkages. Based on
      extensive laboratory experiments, the structure having the repeating units of the
      acidic polysaccharide from sissoo leaves, with unusual branching, was
      established.

PMID- 24751038
TI  - Cotton fabrics treated with novel oxidic phases acting as effective smoke
      suppressants.
AB  - Sol-gel processes have been applied to cotton fabrics in order to coat the fibres
      with a silica film, able to improve their thermo-oxidative resistance and their
      combustion behaviour under the irradiative heat flow of a cone calorimeter. To
      this aim, tetramethoxysilane, inorganic precursor of the silica phase, has been
      employed alone or coupled with species having either smoke suppressant features
      (namely, zinc oxide, zinc acetate dihydrate and zinc borate) or well known flame
      retardant properties (like ammonium pentaborate octahydrate, boron phosphate,
      ammonium polyphosphate and 9,10-dihydro-9-oxa-10-phosphaphenanthrene-10-oxide).
      In addition, the use of barium sulphate, which is a smoke suppressant and, at the
      same time, a flame retardant, has been investigated. Cone calorimetry turned out
      to be a suitable technique for assessing the flammability and smoke production of
      the treated fabrics (particularly when referring to total smoke release, smoke
      production rate and CO and CO2 yields). The composition and morphology of the
      deposited coatings, assessed by scanning electron microscopy, have been found to
      influence their combustion behaviour, as well as their thermal and thermo
      oxidative stability evaluated by thermogravimetric analysis in nitrogen and air,
      respectively.

PMID- 24751039
TI  - Facile synthesis of carboxymethyl curdlan-capped silver nanoparticles and their
      application in SERS.
AB  - Carboxymethyl curdlan (CMc), a beta-D-glucan derivative, was used in the
      photoinduced synthesis of Ag nanoparticles. The size, size distribution,
      morphology and structure of the as-prepared Ag nanoparticles were investigated
      with UV-vis spectroscopy, transmission electron microscopy (TEM), energy
      dispersive X-ray spectrometry (EDX), X-ray diffraction (XRD) and Fourier
      transform infrared (FTIR) spectroscopy. The experimental results indicated that
      the particle size increased and the size distribution became broader with
      increasing the concentrations of both AgNO3 and CMc, and the effect of the latter
      was more pronounced. With the CMc concentration increasing, the diversity of
      morphology was obtained as a result of the plasmon excitation and the role of
      CMc. It was found that CMc played an important role in the synthesis and
      stabilization of Ag nanoparticles through a series of contrastive experiments.
      The enhancement effect of the produced Ag nanoparticles in surface enhanced Raman
      scattering (SERS) was also investigated.

PMID- 24751040
TI  - Study of antimicrobial activity and atomic force microscopy imaging of the action
      mechanism of cashew tree gum.
AB  - The aim of this work was to evaluate the antimicrobial potential of two grades of
      cashew tree gum (crude and purified) against eight microorganisms and to analyze
      the mechanism of cashew tree gum antimicrobial action via atomic force microscopy
      (AFM) imaging. The results indicated strong antimicrobial properties of pure
      cashew tree gum against all tested microorganisms, except for Candida albicans
      and Lactobacillus acidophilus. On the other hand crude cashew gum showed
      antimicrobial activity only against Gram-positive bacteria (MRSA, MSSA, Listeria
      innocua and Enterococcus faecium). Atomic force microscopy imaging showed that
      pure cashew tree gum lead to bacterial cell collapse. In conclusion cashew tree
      gum presented relevant antimicrobial activity against most of the studied
      bacteria, and the purification of the cashew gum affected its antimicrobial
      spectrum. 

PMID- 24751041
TI  - Synthesis, flocculation and adsorption performance of amphoteric starch.
AB  - A novel amphoteric copolymer flocculant was synthesized by incorporating a
      cationic moiety 2,3-epoxypropyl trimethyl ammonium chloride (GTA) and an anion
      moiety phosphate onto the backbone of starch with microwave radiation. The
      synthesized starch copolymer was characterized and examined by FTIR, (1)H NMR
      spectroscopy, scanning electron microscopy (SEM), molecular mass and
      polydispersity, swelling power and solubility index. Flocculation performance was
      evaluated in 50mg/L methyl violet solution. It has been found that these
      flocculation characteristics mainly depended on the charge neutralization,
      followed by the interchain bridging of the amphoteric copolymer. Also, adsorption
      to Pb (II) solution was investigated by jar test. The results showed that the
      adsorption capacity of amphoteric copolymer correlated with pH value, adsorption
      time and initial Pb (II) concentration. 

PMID- 24751042
TI  - Optimization of total polysaccharide extraction from Dioscorea nipponica Makino
      using response surface methodology and uniform design.
AB  - On the base of single factor investigation, effects of extraction temperature,
      extraction time and ratio of water to material as well as their interactions on
      the yield of total polysaccharide from Dioscorea nipponica Makino were studied by
      uniform design and response surface methodology, respectively. The optimal
      process conditions were obtained by response surface methodology as follows:
      ratio of liquid to solid 33:1, extracting duration 134 min, and extracting
      temperature 95  degrees C, under optimized conditions, and the experimental yield
      3.82% agreed closely with the predicted yield 3.9%. The tri-dimensional response
      surfaces were plotted by design-expert, and it was indicated that both extraction
      temperature and extraction time had interaction effects on the response value and
      there were no interaction effects of extraction time and liquid:solid ratio.
      Therefore, the application of response surface methodology in the extraction of
      total polysaccharide from D. nipponica Makino is more significant than uniform
      design.

PMID- 24751043
TI  - Albizia procera gum as an excipient for oral controlled release matrix tablet.
AB  - The purpose of this research was to develop and evaluate controlled release
      matrix tablets of paracetamol based on natural gum exudates of Albizia procera.
      Procera gum was characterized of its properties like compressibility index, angle
      of repose, viscosity and moisture content. The interaction between the gum and
      paracetamol was also studied through differential scanning calorimetry (DSC) and
      FTIR spectroscopy. Matrix tablets were then prepared by wet granulation method
      with different concentrations of procera gum and hydroxypropyl methylcellulose
      (HPMC) and evaluated for their physical properties like weight variation,
      hardness, friability and content uniformity. Dissolution study was conducted to
      characterize release mechanism from the matrix system and data were fitted to
      various kinetic models. The mechanism of drug release from both types of matrix
      tablets was found to be anomalous type. Results from various evaluations
      suggested that A. procera gum could be used as drug release retardant in
      controlled release matrix systems. 

PMID- 24751045
TI  - Mechanical properties and in vitro degradation of electrospun bio-nanocomposite
      mats from PLA and cellulose nanocrystals.
AB  - Fibrous bio-nanocomposite mats consisting of cellulose nanocrystals (CNCs) and
      poly(lactic acid) (PLA) were electrospun from a solvent mixture consisting of
      N,N'-dimethylformamide and chloroform at room temperature. Morphological,
      mechanical and thermal properties, as well as in vitro degradation of
      nanocomposite mats were characterized as a function of material composition.
      Average diameter of the electrospun fibers decreased with increased CNC-loading
      level. Thermal stability, and tensile strength and modulus of nanocomposite mats
      were effectively improved by the addition of CNCs up to the 5 wt% level. The
      reinforcement of CNCs on electrospun mats was illustrated by the observation of
      SEM-based morphologies on the tensile fracturing process of nanocomposite mats.
      At the CNC content of 5 wt%, the maximum tensile stress and Young's modulus of
      the nanocomposite mats increased by 5 and 22 folds than those of neat PLA mats,
      respectively. Moreover, compared with neat PLA mats, the nanocomposite mats,
      especially at high CNC-loading levels, degraded more rapidly in phosphate
      buffered saline solution.

PMID- 24751044
TI  - Antitumor effects of a purified polysaccharide from Rhodiola rosea and its action
      mechanism.
AB  - In the last three decades, numerous polysaccharides and polysaccharide-protein
      complexes have been isolated from plant or animal and used as a promising source
      of therapeutic agents for cancer. In this study, we prepared a homogeneous
      polysaccharide (RRP-ws) from Rhodiola rosea and tested its immunomodulation and
      anti-cancer activity in vitro and in vivo experiments using Sarcoma 180 (S-180)
      cells. Preliminary physicochemical analysis identified that RRP-ws was composed
      of Glc, Gal, Man and Rha with a relative molar ratio of 4.2:2.4:1.6:1.0, and
      contained 95.14% of total carbohydrate, 2.08% of protein and no sulfate. In vitro
      experiment showed that RRP-ws exerted a direct cytotoxic effect on the growth of
      S-180 cells. In vivo experiment, RRP-ws could inhibit tumor growth of S-180 tumor
      transplanted in mice, and increase the relative spleen/thymus indexes and body
      weight. Furthermore, RRP-ws also increased the production of IL-2, TNF-alpha and
      IFN-gamma in serum, and elevated the ratio of CD4+/CD8+ on peripheral blood T
      lymphocyte in tumor bearing mice. The overall findings indicated that RRP-ws
      could be used as a novel promising immunotherapeutic agent in cancer treatment. 

PMID- 24751046
TI  - Compared study on the cellulose/CaCO3 composites via microwave-assisted method
      using different cellulose types.
AB  - The purposes of this study were to explore the influences of different cellulose
      types on the cellulose/CaCO3 composites, which were synthesized via the microwave
      assisted method by using alkali extraction cellulose and microcrystalline
      cellulose, respectively. Experimental results demonstrated that the types of
      cellulose played an important role in the microstructure and morphologies of the
      cellulose/CaCO3 composites. The composites consisted of cellulose and pure phase
      CaCO3 (calcite). The sample synthesized using microcrystalline cellulose had
      better crystallinity than that of the sample using alkali extraction cellulose.
      The cellulose fibers and CaCO3 particles were observed using alkali extraction
      cellulose. However, using microcrystalline cellulose instead of alkali extraction
      cellulose, the cellulose with irregular shape and CaCO3 microspheres were
      obtained. Therefore, choosing appropriate cellulose types is very important for
      the formation of cellulose/CaCO3 composites. Furthermore, the Raman spectra of
      the cellulose/CaCO3 composites were also researched. 

PMID- 24751047
TI  - An effective redox system for bleaching cotton cellulose.
AB  - An effective sodium chlorite/potassium permanganate bleaching system was used to
      bleach cotton fabric without severe loss in the fabric's mechanical properties.
      The bleaching process based on depositing Mn(III) on the fabric surface followed
      by treating the fabric with sodium chlorite solution. Parameters governing the
      bleaching efficiency, like potassium permanganate concentration, sodium chlorite
      concentration and bleaching bath temperature were studied. The bleached fabrics
      were fully characterized by measuring their whiteness index, carboxyl and
      carbonyl contents, percent loss in fabric weight and tensile strength. The
      obtained results reveal that bleached cotton fabric with satisfactory whiteness
      index and reasonable tensile strength can be obtained by soaking the fabric, at
      50  degrees C in potassium permanganate solution (0.01 N), using material to
      liquor ratio of 1:10. The fabric is then rinsed with distilled water, squeezed
      and introduced to bleaching bath containing 5 g/l sodium chlorite and 1 g/l non
      ionic wetting agent using a material to liquor ratio of 1:10.

PMID- 24751048
TI  - Structure of arabinogalactan-protein from Acacia gum: from porous ellipsoids to
      supramolecular architectures.
AB  - The structure of the arabinogalactan-protein (AGP) fraction of the gum exudate of
      Acacia senegal (gum Arabic) isolated from hydrophobic interaction chromatography
      was investigated using HPSEC-MALLS, small angle neutron scattering and TEM
      observations. Literature reported that the AGP structure of gum Arabic adopts a
      very compact conformation in solution due to the attachment of short arabinoside
      side chains and much larger blocks of carbohydrate to the polypeptidic backbone.
      The present study revealed that AGP in solution had a weight average molecular
      weight Mw of 1.86*10(6) g mol(-1) and a radius of gyration Rg of 30 nm. In
      addition, two exponent values were identified in the Rg, [eta], Rh and rho vs. Mw
      relationships highlighting two types of conformations depending on the molecular
      weight range considered: a low molar mass population with long-chain branching
      and a compact conformation and a high molar mass population with short-chain
      branching and an elongated conformation. AGP would behave in solution as a
      branched or hyper-branched polymer with conformations ranging from globular to
      elongated shape depending on the size of the carbohydrate branches. Small angle
      scattering form factor revealed an elongated average conformation corresponding
      to a triaxial ellipsoid while inverse Fourier transform of the scattering form
      factor gave a maximum dimension for AGP of 64 nm. Transmission electron
      microscopy highlighted the existence of two types of flat objects with
      thicknesses below 3-5 nm, single particles with a more or less anisotropic
      spheroidal shape and aggregated structures with a more elongated shape. A
      remarkable feature of all particle morphologies was the presence of an outer
      structure combined to an inner more or less porous network of interspersed chains
      or interacting structural blocks, as previously found for the arabinogalactan
      (AG) main molecular fraction of Acacia gum. However, clear differences were
      observed in the density and morphology of the inner porous network, probably
      highlighting differences in the degree of branching. The existence of assembled
      AG as part of the AGP family was confirmed using TEM micrographs at high
      resolution. Fused AGP dimers, trimers, tetramers and multimers were also
      identified. These molecular assemblies questioned about the nature of
      interactions involved.

PMID- 24751049
TI  - Studies on wheat bran Arabinoxylan for its immunostimulatory and protective
      effects against avian coccidiosis.
AB  - Wheat (Triticum aestivum) bran derived polysaccharides, Arabinoxylans (AXs), were
      evaluated for their immunostimulatory and protective efficacy against Eimeria
      infection in chickens. Humoral response revealed significantly higher (P<0.05)
      total Igs, IgG and IgM titers at days 7th and 14th post primary and secondary
      injections of sheep red blood cells in the experimental chickens administered
      with AXs as compared to those of control group. The percent protection and daily
      weight gains were significantly higher (P<0.05) in the chickens of experimental
      groups as compared to control; whereas, mean oocyst per gram of droppings and
      lesion scores were significantly higher (P<0.05) in control group as compared to
      chickens in the experimental groups. The differences in organ body weight ratio
      of all the lymphoid organs were statistically non-significant (P>0.05) between
      experimental and control groups except thymus and cecal tonsils. In conclusion,
      AXs showed both immunostimulatory and protective effects against coccidiosis in
      broiler chickens. 

PMID- 24751050
TI  - Effects of heat-moisture treatment on normal and waxy rice flours and production
      of thermoplastic flour materials.
AB  - Different levels of heat-moisture treatment (HMT) were applied to normal and waxy
      rice flours. Changes in chemical composition and functional properties of both
      flours were investigated. It was found that HMT induced beta-turn conformation of
      rice proteins. Levels of HMT and types of rice flour interactively influenced
      thermal properties and XRD patterns of flour. When heat-moisture treated flour
      was utilized for production of thermoplastic flour (TPF) materials, it was found
      that HMT improved continuity of injection molding, complete mold filling, and
      yielded homogenous TPF materials. HMT levels affected the mechanical, thermal and
      barrier properties of TPF resin and materials differently. The ratio of HMT level
      to native flours was proposed for use not only for resin processing and injection
      molding, but also for improving mechanical and barrier properties of TPF
      materials. 

PMID- 24751051
TI  - Expression of the heparinase gene from Flavobacterium heparinum in Escherichia
      coli and its enzymatic properties.
AB  - Heparinase has an important application in the preparation of low-molecular
      weight heparins by heparin enzymolysis. A heparinase gene from Flavobacterium
      heparinum was cloned and expressed in Escherichia coli BL21 in order to enhance
      its activity. The expressed heparinase was purified to homogeneity by a metal
      chelating affinity column and its enzymatic properties were evaluated. A maximal
      heparinase activity of 1061 IU/L toward the substrate heparin was achieved when
      the recombinant strain was induced with 0.5 mM isopropyl-beta-D-thiogalactoside
      at 28  degrees C for 9 h. The optimal temperature and pH of heparinase were 30 
      degrees C and 7.0, respectively. The recombinant heparinase was heat-unstable and
      had a higher stability at pHs from 7.0 to 10.0. Observed activities of heparinase
      were the highest in the presence of Ca(2+) and Cu(2+) and the lowest in the
      presence of Mn(2+) and Pb(2+). These results lay a good foundation for the
      preparation of LMWHs by heparin enzymolysis.

PMID- 24751052
TI  - Effect of inulin on rheological and thermal properties of gluten-free dough.
AB  - The aim of the study was to evaluate the influence of inulins with varying degree
      of polymerization on rheological and thermal properties of gluten-free starch
      based dough. The share of inulin reduced the values of consistency coefficient,
      as well as storage and loss moduli, and increased creep compliance. Inulin
      preparation with the highest average degree of polymerization had the strongest
      impact on viscoelastic properties of the obtained dough. The presence of inulin
      also caused a significant decrease of viscosity upon pasting, and an increase of
      gelatinization temperatures TOg, TP1g, TP2g, and TEg. Addition of inulin had no
      effect on gelatinization enthalpy (DeltaHg), while it strongly reduced the
      enthalpies of retrograded amylopectin after storage. Water binding properties of
      inulin seem to be the key factor, responsible for modification of dough
      properties, because they influence solvent availability for other constituents of
      such system. 

PMID- 24751053
TI  - Synthesis of beta-cyclodextrin modified chitosan-poly(acrylic acid) nanoparticles
      and use as drug carriers.
AB  - beta-Cyclodextrin modified chitosan-poly(acrylic acid) nanoparticles (CS-PAACD
      NPs) were obtained by polymerizing acrylic acid (AA) and beta-cyclodextrin (beta
      CD) substituted acrylic acid (AACD) in chitosan (CS) solution. These CS-PAACD
      NPs, characterized by transmission electron microscopy (TEM), scanning electron
      microscopy (SEM) as well as atomic force microscopy (AFM), were quite small in
      size about 40-50 nm. The size and the microstructure of these CS-PAACD NPs could
      be accurately controlled by changing the ration of AACD to AA. As the ratio of
      AACD to AA increased, the size of these NPs decreased. These as-prepared CS-PAACD
      NPs showed enhanced solubility for paclitaxel (PTX) in aqueous solution and
      exhibited a typical pH-sensitive release property for the encapsulated drug in
      vitro. The presence of the beta-cyclodextrin inside the CS-PACD NPs greatly
      enhanced the ability to load hydrophobic drugs, which significantly broadened the
      application of CS-PAACD NPs in biomedical fields.

PMID- 24751054
TI  - Microwave synthesized xanthan gum-g-poly(ethylacrylate): an efficient Pb2+ ion
      binder.
AB  - Microwave induced emulsion copolymerization of ethylacrylate and xanthan gum
      resulted in copolymer samples of different % grafting (%G). The synthesis was
      done in the presence of catalytic amount of KPS as an initiator and the
      adsorption behavior of the copolymer (360%G) was investigated by performing both
      the kinetics and equilibrium studies in batch conditions. The copolymer was
      characterized by different techniques. Several experimental parameters were
      varied to optimize the adsorption conditions. The most favorable pH for the
      adsorption was pH 5, and at this pH the adsorption data were modeled using
      Langmuir and Freundlich isotherms. On the basis of the Langmuir model, Q0 was
      calculated to be 142.86 mg g(-1) for microwave synthesized copolymer (mwXG-g
      PEA). The sorption by mwXG-g-PEA followed pseudo second-order kinetics where a
      linear plot of t/(qt) versus t was obtained, the correlation coefficient (R(2))
      and rate constant at 100 mg L(-1) Pb(II) being 0.994 and 3.013*10(-4)g/(mg min),
      respectively.

PMID- 24751055
TI  - Mixed 3-mono-O-alkyl cellulose: synthesis, structure characterization and thermal
      properties.
AB  - The 3-mono-O-alkyl cellulose samples bearing two different ether moieties, namely
      methyl/ethyl, methyl/n-propyl, and ethyl/n-propyl were synthesized applying
      protecting group technique. The NMR spectra of the peracetylated products
      revealed the regioselectivity of the alkylation as well as the degree of
      substitution of both alkyl moieties. The number average degree of polymerization
      (DPn) monitored by size exclusion chromatography decreases from DPn 117 (Avicel
      PH-101, starting material) to DPn 34 (sample 4f) due to the multi-step synthesis.
      It could be demonstrated that the lower critical solution temperature (LCST) is
      influenced by the degree of substitution of both alkyl groups. For example, LCST
      values between 33 and 58  degrees C were measured for aqueous solutions of 3-mono
      O-ethyl/n-propyl cellulose. On the contrary, the thermal behavior of a physical
      mixture of 3-mono-O-ethyl- and 3-mono-O-n-propyl cellulose, e.g., was controlled
      by the derivative with the lowest LCST.

PMID- 24751056
TI  - Polygalacturonase: production of pectin depolymerising enzyme from Bacillus
      licheniformis KIBGE IB-21.
AB  - Polygalacturonase is an enzyme that hydrolyzes external and internal alpha (1-4)
      glycosidic bonds of pectin to decrease the viscosity of fruits juices and
      vegetable purees. Several bacterial strains were isolated from soil and rotten
      vegetables and screened for polygalacturonase production. The strain which
      produced maximum polygalacturonase was identified Bacillus licheniformis on the
      basis of taxonomic studies and 16S rDNA analysis. The isolated bacterial strain
      produced maximum polygalacturonase at 37  degrees C after 48 h of fermentation.
      Among various carbon sources apple pectin (1.0%) showed maximum enzyme
      production. Different agro industrial wastes were also used as substrate in batch
      fermentation and it was found that wheat bran is capable of producing high yield
      of enzyme. Maximum polygalacturonase production was obtained by using yeast
      extract (0.3%) as a nitrogen source. It was observed that B. licheniformis KIBGE
      IB-21 is capable of producing 1015 U/mg of polygalacturonase at neutral pH.

PMID- 24751057
TI  - Inhibition on calcium oxalate crystallization and repair on injured renal
      epithelial cells of degraded soybean polysaccharide.
AB  - This paper investigated the inhibitory effect of degraded soybean polysaccharide
      (DPS) on the growth of calcium oxalate (CaOxa) crystals. The results were
      compared with that of soybean polysaccharide without degradation (SPS). The data
      showed that DPS exhibited a much higher efficiency to inhibit CaOxa growth and
      stabilize calcium oxalate dihydrate (COD) compared with SPS. As DPS concentration
      increased, the soluble Ca(2+) ions significantly increased, the aggregation
      degree of calcium oxalate monohydrate (COM) crystals decreased, the shape of COD
      crystals became round and blunt, and the Zeta potential on CaOxa crystal surface
      reduced. The above results were all conducive for the inhibition of CaOxa
      crystallization. In addition, DPS displayed a distinct repairing effect on
      oxidative injured renal epithelial cells in African green monkey (Vero), with
      enhanced cell viability and extracellular superoxide dismutase activity after
      repair. The morphologies of the repaired cells and their regulatory capability on
      CaOxa growth were between the control and injured cells. The results indicated
      that the risk of stone formation can be reduced by DPS, and that DPS may be a
      potential green drug to prevent the formation of CaOxa stones. 

PMID- 24751059
TI  - Depolymerized carrageenan ameliorates growth, physiological attributes, essential
      oil yield and active constituents of Foeniculum vulgare Mill.
AB  - Irradiated carrageenan (IC) elicits an array of plant defense responses and
      biological activities in plants. An experiment was carried out in the naturally
      illuminated conditions of net house in order to assess the effects of foliar
      spray of IC on agricultural performance of fennel (Foeniculum vulgare Mill.),
      which is a high-value essential oil bearing medicinal crop used in
      pharmaceutical, food and cosmetic industries. There were applied four IC
      concentrations (40, 60, 80 and 100 mg L(-1)) as foliar sprays. Application of IC
      significantly improved the growth attributes, physiological and biochemical
      parameters, essential oil yield and the contents of main components of essential
      oil of fennel. IC applied at 80 mg L(-1) enhanced these parameters maximally.
      Unirradiated carrageenan and deionized water had no effect on the attributes
      studied. Moreover, GLC analysis revealed a significant increase in the components
      of essential oil, viz. fenchone (4.48-7.82%) and anethole (78.38-86.08%) compared
      to the control.

PMID- 24751058
TI  - Biocomposite fiber of calcium alginate/multi-walled carbon nanotubes with
      enhanced adsorption properties for ionic dyes.
AB  - A bioadsorbent of calcium alginate/multi-walled carbon nanotubes (CA/MWCNTs)
      composite fiber was fabricated by wet spinning and was characterized. Adsorptions
      of methylene blue (MB) and methyl orange (MO) ionic dyes onto CA/MWCNT composite
      fibers were investigated with different MWCNTs content and pH values. The results
      showed that introduction of MWCNTs of CA/MWCNTs composite fiber could not only
      sharply increase the adsorption capacity of MO onto bioadsorbent by 3 times, but
      enhanced the adsorption rate for MB compared to that of native CA fiber.
      Adsorption kinetics was determined by fitting pseudo-first, second-order and the
      intra-particle diffusion models to the experimental data, with the second-order
      model providing the best description of MB and MO adsorption onto CA/MWCNT
      fibers. The equilibrium adsorption data were analyzed by two widely applied
      isotherms: Langmuir and Freundlich. The desorption experiments showed the
      percentage of desorption were found to be 79.7% and 80.2% for MB and MO,
      respectively. 

PMID- 24751060
TI  - Bacterial cellulose/silica nanocomposites: preparation and characterization.
AB  - The preparation and characterization of bacterial cellulose (BC)/silica
      nanocomposites are presented in this paper. BC hydro-gel was immersed in an
      aqueous solution of tetraethoxysilane (TEOS). By pressing the treated BC matrices
      at 120  degrees C and 2 MPa, water-free translucent sheets were obtained. TEOS
      concentration (3, 5 and 7%) and press time (8, 10 and 12 min) were used as
      variable factors. These materials were characterized by different techniques,
      namely FE-SEM, FTIR, SEM, tensile strength and Young's modulus. All composites
      showed good dispersion of the fibers and strong adhesion between the fibers and
      the matrix. FE-SEM observations showed that the nano-scale silica was embedded
      between the voids and micro-fibrils of the BC matrix. Reflecting this structure,
      the maximum Young's modulus and tensile strength of dry BC/silica composites
      improved to 1.46 GPa and 113 MPa, respectively. The tensile strength and Young's
      modulus showed 35 and 18-fold increase (with 7% TEOS), respectively, while the
      same properties were reduced 15 and 10-fold with increase in press time from 8 to
      12 min. FTIR results illustrated strong chemical interactions between the
      cellulose and silica phases. The optimum condition was obtained when the TEOS
      dosage and press time were 7% and 8 min, respectively.

PMID- 24751061
TI  - Photocrosslinking, micropatterning and cell adhesion studies of sodium
      hyaluronate with a trisdiazonium salt.
AB  - Chemically unmodified sodium hyaluronate has been crosslinked by photoinduced
      decomposition of a trifunctional diazonium salt to generate new biomaterials. In
      addition, the photocrosslinking process does not require a photoinitiator. Thin
      films of formulations of sodium hyaluronate and the photocrosslinker at different
      percentages have been processed. Cytotoxicity has been explored and toxicity was
      not observed with the selected cell lines. 2D patterns of controlled geometry
      have been generated by direct laser writing to perform cell adhesion studies.
      Different adhesion behavior of the cell lines, as assessed by vinculin
      immunostaining and scanning electron microscopy, has been observed in the
      polymeric films depending on the degree of photocrosslinking. 

PMID- 24751062
TI  - Terminal-end functionalization of chondroitin sulfate for the synthesis of
      biomimetic proteoglycans.
AB  - Chondroitin sulfate (CS) based bottle brush proteoglycan mimetics may be employed
      to restore tissue functionality. Synthesis of CS bottle brush structures requires
      immobilization of CS at its terminal end. In this study, we investigated
      commercially available natural CS for use in CS bottle brush synthesis. A
      terminal primary amine on CS was identified and utilized to conjugate amine
      reactive vinyl monomers (i.e. acrylic acid and allyl glycidyl ether). Conjugation
      of vinyl monomers to the CS terminal amine was confirmed using a fluorescamine
      assay, (1)H NMR, and ATR-FTIR. CS was also immobilized onto epoxy functionalized
      surfaces via the CS terminal primary amine as confirmed by contact angle
      measurements of surface wettability. Attachment of polymeriziable end groups to
      CS and attachment of CS to functionalized substrates demonstrated here are the
      first steps towards synthesis of CS bottle brush PG mimics. 

PMID- 24751063
TI  - Characterization of high molecular weight dextran produced by Weissella cibaria
      CMGDEX3.
AB  - Exopolysaccharide (EPS) producing Weissella cibaria CMGDEX3 was isolated from
      cabbage on sucrose containing De Man, Rogosa and Sharpe (MRS) agar.
      Dextransucrase activity and dextran yield was found to be 7.1 DSU ml(-1) and 2.4
      g dl(-1), respectively. The structural characterization of purified EPS
      determined by FTIR, (1)H and (13)C NMR spectroscopy demonstrated that W. cibaria
      CMGDEX3 synthesized a linear dextran that predominately had alpha (1->6)
      glycosidic linkages with only a few (3.4%) alpha (1->3) linked branches.
      Molecular mass determination showed that it was a high molecular weight dextran
      of an average >2,000,000 Da. According to our knowledge this is the first report
      on isolation of dextran synthesizing Weissella genus from Pakistan.

PMID- 24751064
TI  - Ultrasonic degradation of aqueous dextran: effect of initial molecular weight and
      concentration.
AB  - Seven dextrans with different initial molecular weight (IMW) were depolymerized
      by ultrasonic treatment. The effects of IMW in a wide range from 9.3*10(3) Da to
      1.7*10(6) Da and solution concentration (1, 10 and 20 mg/mL) on dextran
      degradation were investigated. Changes in weight-average molecular weight (Mw)
      and polydispersity index (D value) were monitored as a function of ultrasonic
      time. Results showed that Mw and D value decreased with increasing time of
      ultrasonic treatment. Moreover, the degradation proceeded faster for higher IMW
      dextrans and more dilute solutions, yielding lower molecular weight dextrans and
      more homologous solutions. Percentage variation of dextran fragments at different
      molecular weight divisions showed that most of the degradation took place in
      larger molecular weight fragments. Ultrasonic treatment is a simple and
      controllable method for producing dextrans with low molecular weight, which are
      more suitable for clinical use.

PMID- 24751065
TI  - Influence of different purification and drying methods on rheological properties
      and viscoelastic behaviour of durian seed gum.
AB  - The aim of the present study was to investigate the effects of different
      purification and drying methods on the viscoelastic behaviour and rheological
      properties of durian seed gum. The results indicated that the purified gum A
      (using isopropanol and ethanol) and D (using hydrochloric acid and ethanol)
      showed the highest and lowest viscosity, respectively. Four drying techniques
      included oven drying (105  degrees C), freeze drying, spray drying and vacuum
      oven drying. In the present work, all purified gums exhibited more elastic (gel
      like) behaviour than the viscous (liquid-like) behaviour (G"<G'). The current
      study revealed that all drying methods led to significantly diminish the elastic
      (G') and viscous modulus (G") of durian seed gum. The freeze-dried gum and oven
      dried (105  degrees C) gum exhibited the highest and lowest viscous modulus (G"),
      respectively.

PMID- 24751066
TI  - Preparation and optimization of surface-treated methotrexate-loaded nanogels
      intended for brain delivery.
AB  - Nanogels loaded with methotrexate (MTX) were prepared via an ionic gelation
      process using chitosan and sodium tripolyphosphate (TPP). The preparation process
      was optimized by a systematic multi-objective-optimization approach in terms of
      the size, poly-dispersity index (PDI), loading efficiency (LE) and loading
      capacity (LC) of the resulting nanocarriers. A combination of the pH of the
      chitosan solution, the addition time of the TPP solution and temperature effects
      accounted for nearly 75% of the variation in nanogel size; the TPP initial
      concentration had a very significant effect on LE (p<0.0001). The final particle
      size (Z-average (r nm)), PDI, LE and LC corresponding to the optimal conditions
      were 59.27 nm, 0.34, 61.82% and 53.68%, respectively. As the ultimate goal, the
      surfaces of the MTX-loaded nanogels were modified by polysorbate 80 for the
      purpose of brain targeting. The cumulative in vitro release profiles of
      surfactant-coated and uncoated nanogels were almost identical and showed
      acceptable performance.

PMID- 24751067
TI  - Method for preparation of planar alginate hydrogels by external gelling using an
      aerosol of gelling solution.
AB  - Preparation of planar alginate hydrogels by external gelling requires slow rate
      of exposure of alginate solution to gelling ions to control gelling process and
      hydrogel properties. We tackled this issue by exposing solution of sodium
      alginate to solution of CaCl2 applied as aerosol at exposure rate of 7.5 mg cm(
      2) s(-1). Gelling conditions varied with respect to concentrations of sodium
      alginate (1-3 wt.%) and CaCl2 (0.5-4 wt.%), exposure time (2.5-40 min), the 2nd
      gelling step in the presence of barium ions, and the storage step. Dimensional
      stability and Young's modulus values were the principal determined quantities to
      examine the correlation between hydrogel properties and gelling protocol. The
      content of calcium ions in hydrogel after gelling by CaCl2 aerosol reveals that
      the maximum binding capacity of calcium ions by alginate chains was reached.
      Obtained data suggest that an unusual gelling mechanism related to exposure of
      sodium alginate to aerosol of gelling solution does not need to be considered
      since the properties of planar alginate hydrogels follow the trends relevant to
      general knowledge about alginate hydrogels.

PMID- 24751068
TI  - Optimization of inulinase production by a newly isolated Aspergillus tubingensis
      CR16 using low cost substrates.
AB  - Production of an extracellular, thermostable inulinase was carried out by a newly
      isolated strain of Aspergillus tubingensis CR16 using wheat bran and corn steep
      liquor (CSL) under solid state fermentation (SSF). Response surface methodology
      (RSM) involving Box Behnken design (BBD) was employed for the optimization of
      process parameters viz. time period of fermentation, % moisture content, inoculum
      size and pH of the medium. Maximum yield of inulinase was 257+/-11.4 U/g,
      obtained by inoculating 5 g of wheat bran with 10(9) spores/ml, at initial 71.2%
      moisture content and pH 6.1 after 103 h of fermentation along with 1358.6+/-0.8
      U/g of invertase activity. Crude inulinase showed maximum activity at 60  degrees
      C and pH 5.0. The enzyme was found to be thermostable retaining about 90% of its
      activity for 4.5 h at 60  degrees C. Fructose was produced as an end product of
      inulin hydrolysis proving that the enzyme produced was exoinulinase.

PMID- 24751069
TI  - A comparison study on the interactions of two oligosaccharides with tobacco cells
      by time-resolved fluorometric method.
AB  - The interactions of tobacco cells with two oceanic oligosaccharides, chitosan
      oligosaccharide (COS) and alginate derived oligosaccharide (AOS) were
      investigated and compared by time-resolved fluorometric method using two Eu(3+)
      complexes as luminescence probes. The binding processes of two oligosaccharides
      and tobacco leaf cells (epidermal and stomatal guard cells) were characterized by
      the luminescence imaging method based on the reaction of tobacco cells with
      oligosaccharide (COS or AOS) conjugated to a highly fluorescent Eu(3+) complex.
      In addition, the concentration changes of indole-3-acetic acid (IAA) and IAA
      related peroxidase produced in the cells during the interaction of
      oligosaccharides (COS or AOS) and tobacco cells were also determined. The results
      indicate that the bioactivity of COS, with faster binding rate to the tobacco
      cells and stronger effect on the IAA generation in the cells, is remarkably
      higher than that of AOS. The comparison study on bioactivities of the two
      oligosaccharides reveals the relationship between structures and bioactivities of
      oligosaccharide, and suggests that COS should be more favorable to be used as a
      promotion reagent of plant growth in agriculture field. 

PMID- 24751070
TI  - Microwave assisted synthesis and characterization of acrylamide grafted gellan,
      application in drug delivery.
AB  - The synthesis of acrylamide-grafted-gellan gum was carried out by microwave
      assisted free radical polymerization using cerric ammonium nitrate (CAN) as redox
      initiator. A series of graft copolymers, varying in amount of acrylamide, CAN and
      microwave irradiation time was prepared. The modified gum was extracted with 20%
      (v/v) methanol to remove the homopolymer formed during polymerization reaction.
      These graft copolymers were characterized by FTIR, (13)C NMR, CHN, SEM,
      rheological studies and DSC studies. Comparison of grafting parameters such as
      grafting efficiency, percentage grafting and percentage conversion were carried
      out among various series of graft copolymers and then correlating it with
      elemental analysis, DSC, viscosity results. The acute oral toxicity study of
      grated gum was evaluated as per OECD guideline. Tablets were prepared by
      incorporating antidiabetic drug metformin hydrochloride (MTF) in grafted gum
      along with excipients. In vitro studies were performed on prepared tablet
      formulations showing release up to 8 h.

PMID- 24751071
TI  - Chondroitin sulfate based nanocomplex for enhancing the stability and activity of
      anthocyanin.
AB  - To improve the structural stability of the potent antioxidant anthocyanin (ATC),
      a nanocomplex was fabricated from intermolecular stacking between chondroitin
      sulfate (CS) and ATC using a simple complexing method in water, without inputting
      high energy or an organic solvent. The physicochemical properties of the
      nanocomplex were evaluated at various feed weight ratios of CS/ATC. The most
      stable nanocomplex was obtained at a CS/ATC weight ratio of 10/1 (WR10). The ATC
      loading content and loading efficiency were 6.3 and 99%, respectively. Its
      diameter was approximately 300 nm with unimodal size distribution. The
      intermolecular stacking state of WR10 was maintained up to 1 MUg/ml of ATC,
      whereas an intermolecular stacking state formed by ATC alone was easily
      dissociated below 16 MUg/ml of ATC. The structural stability of ATC in WR10 was 8
      times higher than that of free ATC at 37  degrees C. Moreover, the complex
      effectively protected the ATC degradation by hydroxyl molecules under high pH
      (above 9) conditions. Finally, cancer cell growth suppression activity was
      measured to determine the in vitro free radical scavenger ability of ATC. The
      WR10 strongly suppressed the Hela cell growth compared with ATC alone. Therefore,
      we conclude that the CS/ATC nanocomplex has a potential for use as a carrier for
      stable antioxidants or water-soluble drugs via intermolecular stacking. These
      nanocomplexes would prove useful for applications in the food and pharmaceutical
      industries.

PMID- 24751072
TI  - Enhancement of amygdalin activated with beta-D-glucosidase on HepG2 cells
      proliferation and apoptosis.
AB  - The growth inhibition and induction of apoptosis brought by amygdalin and
      activated with beta-D-glucosidase were tested for cytoactivity in HepG2 cells.
      The MTT viability assay showed that all samples had effects on HepG2
      proliferation in dose and time response manners. IC50 of stand-alone amygdalin
      and activation with beta-D-glucosidase on the proliferation of HepG2 cells for 48
      h were 458.10 mg/mL and 3.2 mg/mL, respectively. Moreover, apoptotic cells were
      determined by AO/EB (acridine orange/ethidium bromide) fluorescent staining
      method and Annexin V-FITC/PI staining flow cytometry cell cycle analysis. With
      increasing of amygdalin concentration and the incubation time, the apoptotic rate
      was heightened. Compared with the control, there was significant difference
      (p<0.01). Together, these findings indicate that amygdalin had no strong anti
      HepG2 activity; however the ingredients of amygdalin activated with beta-D
      glucosidase had a higher and efficient anti-HepG2 activity. It was therefore
      suggested that this combination strategy may be applicable for treating tumors
      with a higher activity.

PMID- 24751073
TI  - Characterization and antioxidant activity of a polysaccharide extracted from
      Sarcandra glabra.
AB  - Response surface methodology (RSM) was employed to optimize the parameters for
      polysaccharide extracted from the aerial parts of Sarcandra glabra (SGP). The
      optimum conditions were predicted as follows, ratio of water to raw material at
      30, extracting temperature at 85  degrees C, extracting duration at 3 h, and
      yield was estimated at 4.55%. The experimental yield of SGP under the optimum
      conditions was 4.49+/-0.09%. A homogenous polysaccharide (SGP-1) was obtained by
      purification using DEAE-cellulose-52 and Sephacryl S-400 column chromatography.
      SGP-1 showed a single symmetrical peak in high performance size-exclusion
      chromatography (HPSEC) and the average molecular weight (Mw) was estimated to be
      1.06*10(4) Da. It was composed of glucose, galactose, and mannose in a ratio of
      8.38:3.13:1 determined by gas chromatography (GC). The in vitro antioxidant tests
      showed that SGP-1 has significant inhibition effects on hydroxyl, superoxide
      anion, DPPH, ABTS radicals in a dose-dependent manner. This study indicated that
      SGP-1 could be used as a potential natural antioxidant.

PMID- 24751074
TI  - Emulsifying, rheological and physicochemical properties of exopolysaccharide
      produced by Bifidobacterium longum subsp. infantis CCUG 52486 and Bifidobacterium
      infantis NCIMB 702205.
AB  - The rheological, emulsification and certain physicochemical properties of
      purified exopolysaccharides (EPS) of Bifidobacterium longum subsp. infantis CCUG
      52486 and Bifidobacterium infantis NCIMB 702205 were studied and compared with
      those of guar gum and xanthan gum. The two strains were grown in skim milk
      supplemented with 1.5% (w/v) casein hydrolysate at 37  degrees C for 24h; they
      both produced heteropolysaccharides with different molecular mass and
      composition. The carbohydrate content of both polymers was more than 92% and no
      protein was detected. The EPS of B. longum subsp. infantis CCUG 52486 showed
      highly branched entangled porous structure under scanning electron microscopy.
      Higher intrinsic viscosity was observed for the EPS of B. longum subsp. infantis
      CCUG 52486 compared to the EPS of B. infantis NCIMB 702205 and guar gum. Both
      polymers showed pseudoplastic non-Newtonian fluid behaviour in an aqueous
      solution. The EPS of B. infantis NCIMB 702205 and B. longum subsp. infantis CCUG
      52486 produced more stable emulsions with orange oil, sunflower seed oil, coconut
      oil and xylene compared to guar and xanthan gum. The EPS of B. longum subsp.
      infantis CCUG 52486 is the most promising one for applications in the food
      industry, as it had higher intrinsic viscosity, higher apparent viscosity in
      aqueous solution, porous dense entangled structure and good emulsification
      activity.

PMID- 24751075
TI  - Crystallization kinetics of poly(3-hydroxybutyrate-co-3
      hydroxyvalerate)/cellulose nanowhiskers composites.
AB  - In this study, biodegradable poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV)
      films with 1.2-4.6 wt% of cellulose nanowhiskers (CNWs) were manufactured by
      solution casting using N,N-dimethylformide (DMF) as the solvent. Crystallization
      behaviors of PHBV/CNW composites were studied under isothermal conditions using
      differential scanning calorimetry (DSC) and polarized optical microscopy (POM).
      The changes in PHBV crystalline structure were studied using wide angle X-ray
      diffraction (WAXD). Avrami analysis was performed to study the effects of CNW
      concentration and temperature on the crystallization rate and crystallinity of
      PHBV. POM study confirmed the results from the Avrami analysis. In particular,
      the results revealed the dual effects (i.e., nucleation and confinement) of CNWs
      on PHBV nucleation. Depending on the concentration of CNWs, the crystallization
      rate of PHBV could be either increased or decreased due to the combined effects.
      High crystallization temperatures increased the diffusion rate of PHBV chains and
      the growth rate of PHBV spherulites. However, the nucleation effect of CNWs
      decreased at high crystallization temperatures.

PMID- 24751076
TI  - A phenomenological and thermodynamic study of the water permeation process in
      corn starch/MMT films.
AB  - Water transport in edible films of starch based products is a complex phenomenon
      due to the strong interaction of sorbed water molecules with the polymeric
      structure of starch. Moisture sorption isotherms of starch and starch/MMT films
      were obtained. The results indicated that nanoclay incorporation produces a
      decrease of water uptake at all temperatures analysed. Thermodynamic parameters
      showed that sorption process is less favourable when MMT is incorporated into the
      starch matrix. Effect of driving force and water activity (aw) values at each
      side of the film on permeability and diffusivity coefficients were analysed. The
      effect of the tortuous pathway generated by MMT incorporation was significant
      only in the middle and lower range of aw. At high aw range the plasticizing
      effect of water dominated and MMT incorporation had little effect on the water
      barrier properties of these films. 

PMID- 24751077
TI  - Electrospun zein nanofibers incorporating cyclodextrins.
AB  - Zein nanofibers containing cyclodextrins (zein/CD) were produced via
      electrospinning. Three types of CDs (alpha-CD, beta-CD and gamma-CD) having 10%,
      25% and 50% (w/w) were individually incorporated into zein nanofibers. SEM
      imaging elucidated that the morphologies of the electrospun zein/CD nanofibers
      depended on the CD type and weight percentage. The incorporation of CDs in zein
      improved the electrospinnability and bead-free nanofibers were obtained at lower
      zein concentrations. Zein/CD nanofibers having fiber diameters ~100-400 nm were
      obtained depending on the zein concentrations, types and weight percentages of
      CD. XRD studies revealed that CDs were mostly distributed without forming
      crystalline aggregates for zein/CD nanofibers containing lower weight percentage
      of CDs. The surface analyses of zein/CD nanofibers by ATR-FTIR and XPS indicated
      that some of the CDs were present on the fiber surface. Thermal analyses showed
      that zein/beta-CD nanofibers have shown higher glass transition temperatures and
      higher degradation temperature with increasing CD content.

PMID- 24751078
TI  - Biopolymer-based supramolecular micelles from beta-cyclodextrin and
      methylcellulose.
AB  - Supramolecular polymer micelles (SMPMs) were constructed from natural and natural
      derived polymers: beta-cyclodextrin (beta-CD)/maleic anhydride modified beta
      cyclodextrin (MAh-beta-CD) and methylcellulose (MC) in aqueous solution by one
      pot self-assembly procedure, in which, beta-CD and MAh-beta-CD inclusion
      complexes were used as the hydrophilic shell and the free MC as the core. The
      shapes of the SMPMs were regular spheres with diameters of 25+/-5 nm. The
      critical micelle concentrations, calculated from steady-state fluorescence
      emission spectra, were around 15.13 and 20.89 mg/L for MC/beta-CD and MC/MAh-beta
      CD SMPMs, respectively. The in vitro drug release behaviors of the micelles were
      studied using prednisone acetate as a model drug, and the results showed that the
      MC/MAh-beta-CD micelle had a drug-enrichment core and excellent drug released
      behaviors with a sustaining release time of 700 h.

PMID- 24751079
TI  - Cellulose/polycaprolactone blends regenerated from ionic liquid 1-butyl-3
      methylimidazolium chloride.
AB  - Ionic liquid solvent, 1-butyl-3-methylimidazolium chloride (BMIM[Cl]) was used to
      prepare cellulose/polycaprolactone (PCL) blend films. This solvent was recycled
      with high yield and purity after blend precipitation. The inter- and intra
      molecular hydrogen bonding interactions in these blends were investigated by
      Fourier transform infrared (FTIR) spectroscopy and it was found that a new peak
      in the carbonyl region, assigned to hydrogen bonding between carbonyl groups of
      PCL and hydroxyl groups of cellulose in blends with PCL composition less than 40
      wt%. Differential scanning calorimetry (DSC) results implied a partial
      miscibility of the two components by melting point depression. Moreover, the
      tensile properties of the blends can be adjusted by incorporating various amounts
      of PCL into cellulose. The blends show significant enhancement of thermal
      stability compared to the regenerated cellulose when the content of PCL is higher
      than 40 wt%. This work demonstrates an effective approach for the processing
      biodegradable blends from natural and synthetic polymers.

PMID- 24751080
TI  - Polylactide-based renewable composites from natural products residues by
      encapsulated film bag: characterization and biodegradability.
AB  - In the present study, the biodegradability, morphology, and mechanical properties
      of composite materials consisting of acrylic acid-grafted polylactide (PLA-g-AA)
      and natural products residues (corn starch, CS) were evaluated. Composites
      containing acrylic acid-grafted PLA (PLA-g-AA/CS) exhibited noticeably superior
      mechanical properties due to their greater compatibility with CS compared with
      PLA/CS. The feasibility of using PLA-g-AA/CS as a film bag material to facilitate
      the controlled release of an encapsulated phosphate-solubilizing bacterium (PSB)
      Burkholderia cepacia as a fertilizer use promoter was then evaluated. For
      purposes of comparison and accurate characterization, a PLA film bag was also
      assessed. The results showed that the bacterium completely degraded both the PLA
      and the PLA-g-AA/CS composite film bags, resulting in cell release. The PLA-g
      AA/CS (20 wt%) film bags were more biodegradable than those made of PLA, and
      displayed a higher loss of molecular weight and intrinsic viscosity, indicating a
      strong connection between these characteristics and biodegradability.

PMID- 24751081
TI  - Electrospun PCL/phlorotannin nanofibres for tissue engineering: physical
      properties and cellular activities.
AB  - Micro/nanofibrous substrates have been widely used for tissue regeneration
      because of their similarities to extracellular matrix components and their high
      surface area, which facilitates attachment and proliferation of cells.
      Phlorotannin, the main component of the brown alga Ecklonia cava, contains
      various growth factors that promote the regeneration of various tissues,
      including bone, by stimulating alkaline phosphatase (ALP) activity and inducing
      calcium deposition. Despite the benefits of phlorotannin in tissue regeneration,
      the activity of phlorotannin as a component of micro/nanofibres of various
      compositions has not yet been investigated. Here, we fabricated electrospun
      polycaprolactone (PCL)/phlorotannin micro/nanofibres containing different
      phlorotannin concentrations (1, 3, and 5 wt%) and determined their physical
      properties, including water contact angle, water absorption, and mechanical
      properties. Owing to their hydrophilicity and water absorption ability,
      phlorotannin-containing fibrous mats exhibited outstanding wettability compared
      with pure PCL fibrous mats. The biocompatibility of the mats was examined in
      vitro using osteoblast-like cells (MG63). Cell viability, ALP activity, and
      calcium deposition were assessed. The cells distributed more widely and
      proliferated to a greater degree on PCL/phlorotannin mats compared with pure PCL
      mats. In addition, cell viability (at 5 wt% phlorotannin), total protein content,
      ALP activity, and calcium deposition were higher with PCL/phlorotannin mats than
      with pure PCL mats. These results suggest that electrospun PCL/phlorotannin is a
      promising bioactive material for enhancing bone tissue growth.

PMID- 24751082
TI  - Analysis of structural heterogeneity of fucoidan from Hizikia fusiforme by ES-CID
      MS/MS.
AB  - A fucoidan from the brown alga Hizikia fusiforme was extracted with hot water and
      fractionated by anion-exchange chromatography. The main fraction YF5 was
      depolymerized by partial acid hydrolysis and further purified by gel filtration
      chromatograph. The sequences of oligosaccharides generated were then determined
      by ES-CID-MS/MS, which gave directly information on the structural heterogeneity
      of fucoidan from H. fusiforme. It was shown that YF5 had a backbone of a
      repeating disaccharide unit of [->4GlcAbeta1,2Manalpha1->], in good agreement
      with previous report by NMR and methylation analysis. In the product-ion spectra,
      the unique (0.2)A type fragmentation was important to establish the presence of a
      2-linked Man in the backbone structure. In addition, abundant novel heterogeneous
      branched structural fragments were also detected and characterized: Fuc1,3Fuc,
      Fuc1,3Gal, Fuc1,4GlcA, Gal1,4Gal, Gal1,4GlcA and GlcA1,4GlcA. The sulfation
      mainly occurred at C2 or C4 of the fucose residue and C2, C4 or C6 of the
      galactose residue.

PMID- 24751083
TI  - Synthesis and antiherpetic activity of carboxymethylated and sulfated hyaluronan
      derivatives.
AB  - Native high molecular weight hyaluronan (HMW-HA, MW=1*10(6) g/mol) and a
      thermally degraded low molecular weight hyaluronan (LMW-HA, MW=1.3-1.4*10(5)
      g/mol) were carboxymethylated providing products with degrees of
      carboxymethylation (DSCM) of up to 0.8. Sulfation of resulting carboxymethyl
      hyaluronan (CM-HA) and hyaluronan (HA) was performed by different sulfation
      procedures enabling the control of the degree of sulfation (DSS) in the obtained
      new carboxymethyl hyaluronan sulfates (CM-HA-S) and hyaluronan sulfates (HA-S),
      respectively, in a range between 0.9 and 3.3. Both carboxymethylation and
      sulfation were found to take place preferentially at the primary hydroxyl groups
      of HA. The antiviral activity of these synthesized HA derivatives was tested
      against Herpes simplex virus type 1. Both HA-S and CM-HA-S derivatives with high
      DSS values of about 3.0 exhibit a strong antiherpetic activity. The CM-HA
      derivatives were found to be not active and an additional effect of introduced
      carboxymethyl groups on the antiherpetic activity of CM-HA-S derivatives was not
      observed. In the case of HA-S, the antiviral efficacy can be correlated with the
      DSS and becomes stronger with increasing DSS values.

PMID- 24751084
TI  - Occurrence of amylose-lipid complexes in teff and maize starch biphasic pastes.
AB  - The occurrence of amylose-lipid complexes was determined in maize and teff starch
      biphasic pastes i.e. peak viscosity pastes at short and prolonged pasting times.
      Maize and teff starches were pasted for 11.5 and 130 min with or without added
      stearic acid followed by thermo-stable alpha-amylase hydrolysis in a rapid visco
      analyzer. X-ray diffraction analysis of pastes before and residues after
      hydrolysis showed crystalline V-amylose diffraction patterns for the starches
      pasted for a prolonged time with added stearic acid while less distinct V-amylose
      patterns with non-complexed stearic acid peaks were observed with a short pasting
      time. Differential scanning calorimetry of pastes before and residues after paste
      hydrolysis showed that Type I amylose-lipid complexes were formed after pasting
      for the short duration with added stearic acid, while Type II complexes are
      formed after pasting for the prolonged time. The present research provides
      evidence that amylose-lipid complexes play an important role in starch biphasic
      pasting.

PMID- 24751085
TI  - Graft polymerization of acrylic acid onto chitin nanofiber to improve
      dispersibility in basic water.
AB  - Graft copolymerization of acrylic acid (AA) on chitin nanofibers was carried out
      with potassium persulfate as a free radical initiator in an aqueous medium. The
      molar ratio of grafted AA increased with the AA concentration. The grafted chitin
      nanofibers were characterized by FT-IR, FE-SEM, UV-vis, XRD, and TGA. After
      polymerization, the characteristic morphology of chitin nanofibers was
      maintained. Chitin nanofibers grafted with AA were efficiently dissociated and
      dispersed homogeneously in basic water because of the electrostatic repulsion
      effect between nanofibers. AA was grafted on the surface and amorphous part of
      chitin nanofibers, and the original crystalline structure of alpha-chitin was
      maintained. At 330  degrees C, the weight residue of the graft copolymer
      increased with the grafted AA content.

PMID- 24751086
TI  - Immersion mode material pocket dynamic mechanical analysis (IMP-DMA): a novel
      tool to study gelatinisation of purified starches and starch-containing plant
      materials.
AB  - There is a clear need for improved methods for the study of the physical changes
      that occur in slurries and sol-gel systems that have significant water content.
      In this paper a novel immersion mode material pocket form of dynamic mechanical
      analysis (IMP-DMA) has been designed, combining material pocket technology to
      provide physical support to a powdered sample within an immersion bath. IMP-DMA
      allows the mechanical response of a powder during heating to be monitored in
      excess water. IMP-DMA was evaluated using a range of starch samples loaded as a
      slurry into a solid steel pocket, the mechanical responses of these samples were
      monitored as a function of temperature, and values for modulus and tandelta peaks
      were found to correspond well with events occurring at both the onset and peak
      gelatinisation temperatures as measured by differential scanning calorimetry
      (DSC) (e.g. wheat starch has an onset and peak DSC temperature of 49.3  degrees C
      and 57.2  degrees C, respectively, and shows a peak in tandelta at 52.8  degrees
      C and a modulus peak at 57.7  degrees C). Some limitations were found in the
      ability of DMA to detect transitions in starches with low or high amylose
      contents. IMP-DMA was shown to be an effective tool for monitoring the changes in
      starch structure that occur during gelatinisation, both in purified starches and
      in more complex starch-containing food materials. Thus, a new hyphenated form of
      DMA is now available that permits the thermally induced transitions of particle
      water dispersions to be characterised.

PMID- 24751087
TI  - Carboxymethyl gum kondagogu: synthesis, characterization and evaluation as
      mucoadhesive polymer.
AB  - The objective of the study was to modify gum kondagogu by carboxymethylation and
      to evaluate it for potential pharmaceutical applications. Carboxymethylation of
      gum kondagogu was carried out by reacting gum kondagogu with monochloroacetic
      acid under alkaline conditions. The results of characterization studies revealed
      that carboxymethylation of gum kondagogu increases its degree of crystallinity
      and surface roughness, reduces its viscosity and improves its mucoadhesive
      properties. Further, carboxymethyl gum kondagogu was explored for pharmaceutical
      applications by formulating ionotropically gelled beads using metformin as the
      model drug and calcium chloride as cross-linking agent. Ex vivo bioadhesion study
      conducted using isolated chick-ileum by wash-off test revealed bioadhesion of
      >80% over a period of 24 h. It was observed that increasing the concentration of
      cross-linking agent increases the % drug entrapment and reduces the release rate.
      The beads were found to release the drug by Fickian-diffusion mechanism and
      following zero-order release kinetics.

PMID- 24751088
TI  - Colloidal stability of negatively charged cellulose nanocrystalline in aqueous
      systems.
AB  - Colloidal stability of negatively charged cellulose nanocrystalline (CNC) in the
      presence of inorganic and organic electrolytes was investigated by means of
      dynamic light scattering and atomic force microscopy. CNC could be well dispersed
      in distilled water due to the electrostatic repulsion among negatively charged
      sulfate ester groups. Increasing the concentration of inorganic cation ions
      (Na(+) and Ca(2+)) resulted in CNC aggregation. CNC in divalent cation ion Ca(2+)
      solution exhibited less stability than that in monovalent cation ion Na(+)
      solution. Organic low-molecular-weight electrolyte sodium dodecyl sulfate (SDS)
      favored the stability of CNC suspension, whereas organic high-molecular-weight
      electrolyte sodium carboxymethyl cellulose (CMC) induced CNC particle aggregation
      due to intermolecular bridging interaction or entanglement. Cationic
      polyacrylamide (CPAM) caused a serious aggregation of CNC particles even at low
      concentration of CPAM. At low ionic strength (Na(+), 1 mM), CNC were stable in
      aqueous solution at the pH range of 2-11.

PMID- 24751089
TI  - Infrared study on deuteration of highly-crystalline chitin.
AB  - We report an infrared study of the deuteration of highly crystalline alpha- and
      beta-chitin. With exposure to D2O vapor, the deuteration of alpha-chitin
      progressed on surface molecules, in contrast with beta-chitin, which is partially
      deuterated on the inner part of the crystal. The intracrystalline deuteration
      occurred with high-temperature annealing in liquid D2O for alpha- and beta
      chitin. In alpha-chitin, the deuteration was similar between all the three
      functional groups. The ratio of deuterium/hydrogen increased with treatment
      temperature, and all the hydrogen in the functional groups was accessible above
      200  degrees C. In beta-chitin, the deuteration was more specific for each
      functional group. The deuteration of O3-H groups progressed rapidly, even below
      100  degrees C, and, by contrast, that of O6-H and N-H progressed relatively
      slowly. These differences of deuteration between alpha- and beta-chitin
      presumably arises from the particular ability of beta-chitin to form a complex
      with water molecules.

PMID- 24751090
TI  - Wound dressing based on nonwoven viscose fabrics.
AB  - Nonwoven viscose fabric was treated with chitosan/polyvinyl alcohol (PVA) using
      pad-dry method, using different concentrations of chitosan and PVA. Increasing
      the amount of PVA leads to increasing of air permeability. Water permeability
      increased by increasing the amount of PVA to 2 ml (10% solution) then decreased
      by any increase of the quantity of PVA solution. Roughness increased with
      increasing the amount of 10% PVA solution. It is shown that roughness, water and
      air permeability increased with increasing the chitosan concentration.
      Antibacterial properties was increased with increasing PVA/or chitosan
      concentration. The chitosan/PVA treated nonwoven viscose fabric was immersed in a
      solution of Ag nanoparticles. The chitosan/PVA/Ag nanoparticles treated nonwoven
      fabrics were used as wound dressings on French white Bouscat rabbits, with age
      ranged from 1 to 2 years. A complete healing was achieved using wound dressing
      consists of nonwoven viscose fabric treated with chitosan/PVA/Ag nanoparticles
      after 21 days. The histopathological examination confirmed the complete re
      epithelialization and averagely thick epidermis formation.

PMID- 24751091
TI  - Thermal behavior and gelling interactions of Mesona Blumes gum and rice starch
      mixture.
AB  - In this research, thermal behavior and gelling interactions of Mesona Blumes gum
      (MBG)/rice starch mixture were extensively investigated. MBG/rice starch gel
      displayed significant endothermal and exothermal properties at different MBG
      concentrations, indicating essential interactions between MBG and rice starch. In
      addition, the gelling interaction between MBG and rice starch was studied by
      using hydrogen-bond forming agents (1,4-butanediol, ethane-1,2-diol, glycerol)
      and hydrogen-bond breaking agents (urea, tetramethyl urea, ethanol, methanol) on
      rheological spectra. The results indicated that the hydrogen bond between MBG,
      rice starch and water might be the major force of maintaining the complete
      structure of the mixed gel. Their hypothetic interactions have been schemed in
      computer using hyperchem 8.0.

PMID- 24751092
TI  - Structural investigation of an extracellular polysaccharide produced by the
      cariogenic bacterium Streptococcus mutans strain UA159.
AB  - The structure of an extracellular polysaccharide EPS159 produced from sucrose by
      Streptococcus mutans UA159 was investigated through the main oligosaccharides
      obtained from partial acid hydrolysis, monosaccharide/methylation analysis, and
      1D/2D (1)H NMR spectroscopy. The results showed that EPS159 contained terminal, 3
      substituted, 6-substituted, and 3,6-disubstituted alpha-D-glucopyranose residues
      in a molar percentage of 14, 18, 54, and 14%. The backbone of EPS159 was composed
      of ->6)Glcp(1-> residues, and about 20% of the ->6)Glcp(1-> residues was
      substituted at 3-OH by ->3)Glcp(1-> and/or Glcp(1-> residues to form side chains.
      A composite model of EPS159, that includes all identified structural features,
      was formulated: [Formula, see text:].

PMID- 24751093
TI  - Structural elucidation and bioactivity of a novel exopolysaccharide from
      endophytic Fusarium solani SD5.
AB  - A bioactive exopolysaccharide [EPS (PS-I)], having Mw~1.87*10(5) Da was produced
      by submerged culture of an endophytic fungus Fusarium solani SD5. Structural
      elucidation of the EPS (PS-I) was carried out by a series of experiments. Result
      indicates the presence of terminal alpha-L-rhamnopyranosyl, (1->2)-alpha-L
      rhamnopyranosyl, (1->4)-beta-D-galactopyranosyl, (1->4,6)-beta-D-galactopyranosyl
      moieties in a molar ratio of nearly 1:1:3:1. TEM image showed fibril structure of
      the EPS with a diameter of approximately 1 nm. Melting point range of the EPS was
      found 172-178  degrees C. The isolated PS-I exhibit in vitro anti inflammatory
      and anti allergic activity. EPS (1000 MUg/ml) protects 55% erythrocytes from
      hypotonic solution induced membrane lysis. Compound 48/80 induced mast cell
      degranulation was also protected by 56% with 100 MUg/ml EPS.

PMID- 24751095
TI  - Viscosity properties of acetylated carboxymethyl starch.
AB  - The viscosity properties of acetylated carboxymethyl starch (ACMS) aqueous
      solution with different DS (degree of substitution) at concentration of 2.0%
      (w/w) were investigated using Brookfield R/S+ Portable rheometer. All flow curves
      of ACMS are well fitted to Power law model. Arrhenius model was used to describe
      temperature sensitivity. Furthermore, the parameters, which influenced the
      viscosity properties of the solutions, including temperature, DS of carboxymethyl
      group (DScm), DS of acetyl group (DSac), presence of salt (NaCl) and shear rate
      were discussed in detail. Specifically, the viscosity-stability, salt-tolerance
      and shear-resistance of ACMS with DScm (0.76) and DSac (0.34) were compared with
      that of sodium alginate as thickener in food or non-food applications. The
      results indicate that the viscosity properties of ACMS (DScm=0.76, DSac=0.34)
      were similar to that of sodium alginate and ACMS with DScm (0.76) and DSac (0.34)
      may be considered as a substitute for sodium alginate in certain application.

PMID- 24751094
TI  - One-pot synthesis of poly(N-isopropylacrylamide)/chitosan composite microspheres
      via microemulsion.
AB  - This work presents a new approach for the synthesis of multiresponsive composite
      microspheres of PNIPAM/chitosan. The resulting microspheres in a sandwich
      structure with PNIPAM nanoparticles embedded in the crosslinked chitosan matrix
      were characterized. Compared to other preparation methods, this proposed
      technique not only is a facile route but also endows the microspheres a desirable
      structure. The products undergo a temperature induced volume phase transition and
      exhibit an appreciable pH response. They are further tested as drug carriers to
      investigate potential application. The encapsulation efficiency in acidic
      environment (pH=4.0) is 73.5% and much higher than that in neutral (20.3%,
      pH=6.9) and alkaline (15.1%, pH=9.2) environments. The release of the drug from
      the microspheres can be controlled by pH and temperature. 

PMID- 24751096
TI  - High-performance thermotropic starch-based liquid crystalline polymer.
AB  - A thermotropic starch liquid crystalline polymer (St-10CN) was successfully
      synthesized by high-degree substitution (esterification) of the hydroxyl groups
      resided on the starch with mesogenic 11-(4'-cyano-biphenyl-4-yloxy)-undecanoic
      chloride in the presence of pyridine. The degree of substitution of St-10CN was
      calculated to be 2.68 based on the result of elemental analysis. The chemical
      structure of the polymer was confirmed using Fourier transfer infrared (FTIR)
      spectroscopy and nuclear magnetic resonance spectroscopy. The thermal transitions
      of St-10CN were determined using differential scanning calorimetry and its
      mesophase structures were characterized using polarized optical microscopy (POM)
      and wide-angle X-ray diffraction (WAXD). This unique starch-based side-chain
      liquid crystalline polymer is glassy and smectic with excellent thermal
      stability, and has tensile strength of 37.9+/-7.0 MPa and Young's modulus of
      1.42+/-0.14 GPa.

PMID- 24751097
TI  - Biocomposites reinforced with cellulose nanocrystals derived from potato peel
      waste.
AB  - This study investigated the effectiveness of cellulose nanocrystals derived from
      potato peel waste as a reinforcement and vapor barrier additive. The nanocrystals
      were derived from cellulosic material in the potato peel by alkali treatment and
      subsequently acid hydrolysis. TEM images revealed the average fiber length of the
      nanocrystals was 410 nm with an aspect ratio of 41; its aspect ratio being
      considerably larger than cotton-derived nanocrystals prepared using similar
      reaction conditions. Cellulose nanocrystals (CNC)-filled polyvinyl alcohol (PVA)
      and thermoplastic starch (TPS) films were prepared by solution casting method to
      maintain uniform dispersion of the 1-2% (w/w) filler content. An increase of 19%
      and 33% (starch composite) and 38% and 49% (PVA composite) in tensile modulus was
      observed for the 1% and 2% CNC-reinforced composites, respectively. Water vapor
      transmission measurements showed a marginal reduction of water permeability for
      the PVA composite, whereas no effect was observed for the thermoplastic starch
      composite.

PMID- 24751098
TI  - Evaluation of biocomposite films containing alginate and sago starch impregnated
      with silver nano particles.
AB  - In recent years, the metal nanoparticles/polymer composites have created lot of
      attraction due to their wide range of applications. In the present study, the
      composite films of alginate (AL) and sago starch (SG) impregnated with silver
      nano particles (AgNP) with and without antibiotic gentamicin (G) were prepared by
      solvent casting method. The films prepared were characterized for thermo
      gravimetric analysis, SEM, TEM and mechanical properties and the results have
      shown the composite nature of the films. AL-SG-AgNP and AL-SG-AgNP-G composites
      were used as wound dressing materials in experimental wounds of rats. The healing
      pattern of the wounds was evaluated by planimetric studies, macroscopic
      observations, biochemical studies and histopathological observations. The results
      have shown faster healing pattern in the wounds treated with AL-SG-AgNP and AL-SG
      AgNP-G composites compared to untreated control. This study revealed that AL-SG
      AgNP film might be a potential and economical wound dressing material.

PMID- 24751099
TI  - Fabrication of chitin/poly(3-hydroxybutyrate-co-3-hydroxyvalerate) hydrogel
      scaffold.
AB  - Regeneration of skin after a large area wound or burn is often difficult without
      the aid of a scaffold. In this work we developed a 3D macroporous chitin/poly(3
      hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) hydrogel blend by normal solution
      chemistry and lyophilized it to get the scaffold. The developed scaffold was then
      characterized and it showed a slow degrading as well as biocompatible nature. The
      blend hydrogel scaffold showed 67% porosity and the pore size was less than 20
      MUm. Cytocompatibility of the scaffold was proved by Alamar blue assay using
      Human Dermal Fibroblast cells (HDF). The blend hydrogel scaffold showed a two
      fold increase in cell number over control within three days of culture. The
      chitin/PHBV blend also showed enhanced HDF cell attachment and proliferation.
      These preliminary results prove its suitability for scaffold based skin tissue
      regeneration.

PMID- 24751100
TI  - Solvent infusion processing of all-cellulose composite materials.
AB  - Continuous fibre-reinforced all-cellulose composite (ACC) laminates were produced
      in the form of a dimensionally thick (>1 mm) laminate using an easy-to-use
      processing pathway termed solvent infusion processing (SIP) from a rayon
      (CordenkaTM) textile using the ionic liquid 1-butyl-3-methylimidazolium acetate.
      SIP facilitates the infusion of a solvent through a dry cellulose fibre preform
      with the aim of partially dissolving the outer surface of the cellulose fibres.
      The dissolved cellulose is then regenerated by solvent exchange to form a matrix
      phase in situ that acts to bond together the undissolved portion of the fibres.
      SIP is capable of producing thick, dimensionally stable ACC laminates with high
      volume fractions of continuous fibres (>70 vol.%) due to the combination of two
      factors: (i) homogeneous and controlled partial dissolution of the fibres and
      (ii) the application of pressure during regeneration and drying that provides a
      high level of fibre compaction, thereby overcoming void formation associated with
      material shrinkage. The effect of inlet and outlet positioning, and applied
      pressure on the macro- and microstructure of all-cellulose composites is
      examined. Finally, SIP expands the applications for ACCs by enabling the
      production of thick ACC laminates to overcome the limitations of conventional
      thin-film ACCs.

PMID- 24751102
TI  - SarahElizabeth Stewart.

PMID- 24751103
TI  - Components of priming-induced resistance to Fusarium head blight in wheat
      revealed by two distinct mutants of Fusarium graminearum.
AB  - Two mutants (tri6Delta and noxABDelta) of the fungal pathogen Fusarium
      graminearum were assessed for their ability to prime immune responses in wheat
      (cv. Roblin) against challenge with pathogenic F. graminearum. Priming treatments
      generated Fusarium head blight (FHB)-resistant wheat phenotypes and reduced the
      accumulation of fungal mycotoxins in infected tissues. Microarray analysis
      identified 260 transcripts that were differentially expressed during the priming
      period. Expression changes were observed in genes associated with immune
      surveillance systems, signalling cascades, antimicrobial compound production,
      oxidative burst, secondary metabolism, and detoxification and transport.
      Specifically, genes related to jasmonate, gibberellin and ethylene biosynthesis
      exhibited differential expression during priming. In addition, the induction of
      the phenylpropanoid pathways that lead to flavonoid, coumarin and hydroxycinnamic
      acid amide accumulation was also observed. This study highlights the utility of
      nonpathogenic mutants to both elicit and delineate stages of defence responses in
      wheat. 

PMID- 24751104
TI  - Neurokinin-1 receptor expression and antagonism by the NK-1R antagonist
      maropitant in canine melanoma cell lines and primary tumour tissues.
AB  - We interrogated the neurokinin-1 receptor (NK-1R)/substance P (SP) pathway in
      canine melanoma tumour tissues and cell lines. NK-1R messenger RNA (mRNA) and
      protein expression were observed in the majority of tumour tissues.
      Immunohistochemical assessment of archived tissue sections revealed NK-1R
      immunoreactivity in 11 of 15 tumours, which may have diagnostic, prognostic and
      therapeutic utility. However, we were unable to identify a preclinical in vitro
      cell line or in vivo xenograft model that recapitulates NK-1R mRNA and protein
      expression documented in primary tumours. While maropitant inhibited
      proliferation and enhanced apoptosis in cell lines, in the absence of documented
      NK-1R expression, this may represent off-target effects. Furthermore, maropitant
      failed to suppress tumour growth in a canine mouse xenograft model derived from a
      cell line expressing mRNA but not protein. While NK-1R represents a novel target,
      in the absence of preclinical models, in-species clinical trials will be
      necessary to investigate the therapeutic potential for antagonists such as
      maropitant. 

PMID- 24751105
TI  - Rs7574865 polymorphism in signal transducers and activators of transcription 4
      gene and rheumatoid arthritis: an updated meta-analysis of 28 case-control
      comparisons.
AB  - OBJECTIVES: The objective of the present meta-analysis was to investigate whether
      the combined evidence shows an association between the STAT4 rs7574865
      polymorphism and RA. METHODS: A systematic search of all relevant studies
      published through April 2013 was conducted using MEDLINE, EMBASE, OVID, and
      ScienceDirect. The observational studies that were related to an association
      between the STAT4 rs7574865 polymorphism and RA were identified. The association
      between the STAT4 rs7574865 polymorphism and RA susceptibility was assessed using
      genetic models. RESULTS: Seventeen case-control studies with a total of 28
      comparisons (25 300 RA patients and 26 326 controls) met the inclusion criteria.
      A meta-analysis was conducted for genotype TT versus GT+GG, GT+TT versus GG, TT
      versus GG and T-allele. The meta-analysis showed an association between RA and
      the STAT4 rs7574865 TT genotype, GT+TT genotype and T-allele in all subjects.
      Stratification of RA patients according to ethnic group showed that the TT
      genotype, GT+TT genotype and T-allele were significantly associated with RA in
      Europeans, Asians, Africans and Latin Americans. A subgroup analysis according to
      the absence or presence of rheumatoid factor (RF) and anti-cyclic citrullinated
      peptide (anti-CCP) antibodies revealed that the association between the STAT4
      rs7574865 polymorphism and RA may be independent of the presence of RF and anti
      CCP antibodies. CONCLUSIONS: This meta-analysis demonstrated that the STAT4
      rs7574865 polymorphism confers susceptibility to RA in major ethnic groups. The
      association may not be dependent on the presence of RF and anti-CCP antibodies.

PMID- 24751106
TI  - The TAILOR study: to agree or to disagree?

PMID- 24751107
TI  - Comparison between CT tumor size and pathological tumor size in frozen section
      examinations of lung adenocarcinoma.
AB  - OBJECTIVE: We examined the appropriate measurement for pathological tumor size by
      comparing radiological and pathological tumor size of resected lung
      adenocarcinoma in FSE. MATERIALS AND METHODS: We reviewed records of 59 resected
      specimens of lung adenocarcinoma for FSE from January to December 2008. Specimens
      were well-inflated with saline by using an injector before cutting into segments.
      After selecting the tumor segment of maximal diameter, we compared three ways of
      measuring pathological tumor size by using paired t-test: (I) macroscopic tumor
      size (MTS), measured with a metal straight ruler, (II) microscopic frozen section
      tumor size (FSTS), and (III) microscopic paraffin section tumor size (PSTS). We
      compared each discrepancy rate (DR) [DR=(CT tumor size-pathological tumor
      size)/CT tumor size*100] (%) between tumors that were air-containing type and
      solid-density type on CT scans, and also compared the tumors with lepidic
      component rates (LCR) >=50% and LCR <50%, by using Mann-Whitney U-tests. RESULTS:
      FSE could diagnose malignancy with 100% accuracy. The mean CT tumor size was
      18.36mm, and the mean pathological tumor sizes (MTS, FSTS, and PSTS) were 17.81,
      14.29, and 14.23mm, respectively. FSTS and PSTS were significantly smaller than
      CT tumor size (p<0.001). The DR calculated with PSTS was significantly larger in
      air-containing than in solid-density tumors, and also larger in LCR >=50% than in
      LCR <50% tumors. CONCLUSION: FSE with the inflation method diagnosed malignancy
      with 100% accuracy. The lung specimen must be sufficiently inflated to prevent
      tissue shrinking, and we propose MTS as the definition for pathological tumor
      size in FSE. The greater discordance observed between CT tumor size and
      microscopic tumor size was assumed to be due to shrinkage of the lepidic
      component in the tumor.

PMID- 24751108
TI  - RNA sequencing identifies novel markers of non-small cell lung cancer.
AB  - INTRODUCTION: The development of reliable gene expression profiling technology
      increasingly impacts our understanding of lung cancer biology. Here, we used RNA
      sequencing (RNA-Seq) to compare the transcriptomes of non-small cell lung cancer
      (NSCLC) and normal lung tissues and to investigate expression in lung cancer
      tissues. METHODS: We enrolled 88 male patients (mean age, 61.2 years) with NSCLC.
      RNA-Seq was performed on 88 pairs of NSCLC tumor tissue and non-tumor tissue from
      54 patients with adenocarcinoma and 34 patients with squamous cell carcinoma.
      Immunohistochemistry was performed to validate differential candidate gene
      expression in a different NSCLC group. RESULTS: RNA-Seq produced 25.41 * 10(6)
      (+/- 8.90 * 10(6)) reads in NSCLC tissues and 24.70*10(6) (+/- 4.70 * 10(6))
      reads in normal lung tissues [mean (+/- standard deviation)]. Among the genes
      expressed in both tissues, 335 were upregulated and 728 were downregulated >= 2
      fold (p < 0.001). Four upregulated genes - CBX3, GJB2, CRABP2, and DSP - not
      previously reported in lung cancer were studied further. Their altered expression
      was verified by immunohistochemistry in a different set of NSCLC tissues (n =
      154). CBX3 was positive in 90.3% (139 cases) of the samples; GJB2, in 22.7% (35
      cases); CRABP2, in 72.1% (111 cases); and DSP, in 17.5% (27 cases). The positive
      rate of CRABP2 was higher in adenocarcinoma than squamous cell carcinoma (p <
      0.01). CONCLUSIONS: CBX3 and CRABP2 expression was markedly increased in lung
      cancer tissues and especially CRABP2 may be promising candidate genes in lung
      adenocarcinoma.

PMID- 24751109
TI  - Volume replacement following severe postpartum hemorrhage.
AB  - Severe postpartum hemorrhage (PPH) can be defined as a blood loss of more than
      1500 mL to 2500 mL. While rare, severe PPH is a significant contributor to
      maternal mortality and morbidity in the United States and throughout the world.
      Due to the maternal hematologic adaptation to pregnancy, the hypovolemia
      resulting from hemorrhage can be asymptomatic until a large amount of blood is
      lost. Rapid replacement of lost fluids can mitigate effects of severe hemorrhage.
      Current evidence on postpartum volume replacement suggests that crystalloid
      fluids should be used only until the amount of blood loss becomes severe. Once a
      woman displays signs of hypovolemia, blood products including packed red blood
      cells, fresh frozen plasma, platelets, and recombinant factor VIIa should be used
      for volume replacement. Overuse of crystalloid fluids increases the risk for
      acute coagulopathy and third spacing of fluids. A massive transfusion protocol is
      one mechanism to provide a rapid, consistent, and evidence-based team response to
      this life-threatening condition. 

PMID- 24751110
TI  - Experimental ex vivo traumatic intrusion in the mandibular incisors of the farm
      pig, Sus scrofa.
AB  - BACKGROUND/AIM: Traumatic intrusion of incisor teeth occurs frequently in young
      children, as well as in teens and adults; however, the biological mechanisms
      promoting negative sequelae or recovery are not well understood (Oral Surg Oral
      Med Oral Pathol Oral Radiol Endod 2009;107:493 and Vital Health Stat 11
      2007;248:1). Modeling intrusive trauma and post-traumatic healing in an animal
      model offers the opportunity to define these biological mechanisms and to inform
      the design of treatments. The objective of this study was to investigate the pig,
      Sus scrofa, as a model for intrusive trauma, using an in vitro approach.
      MATERIALS AND METHODS: Mandibular segments from ex vivo farm pigs were bisected
      and primary central incisors were prepared to either receive axial traumatic
      loads or to serve as non-intruded controls. A class 2 lever modeled traumatic
      impact to the incisors. Damage to the periodontal support in intruded and control
      specimens (n = 10) was evaluated through compression testing and comparison of
      elastic moduli. Incisor displacement was measured on X-ray images taken before
      and after trauma, and following compressive tests. RESULTS: Lingual x-rays showed
      a mean postinjury displacement of the incisor root of 3.81 +/- 1.87 mm. With
      compression testing, the root length embedded in bone increased in traumatized
      and non-traumatized teeth by 2.9 mm and 0.81 mm, respectively (P = 0.03). The
      intrusion group Young's modulus was significantly lower than the control group
      (4452 vs 7704 Mpa; P = 0.05). CONCLUSION: In vitro modeling of traumatic
      intrusion resulted in damage to the periodontal support of central incisors and
      axial tooth displacement. Pig incisors offer an important model for further study
      of incisor trauma.

PMID- 24751111
TI  - Design, synthesis, anti-tobacco mosaic virus (TMV) activity, and SARs of 7
      methoxycryptopleurine derivatives.
AB  - A series of 7-methoxycryptopleurine derivatives 2-23 were prepared and evaluated
      for their antiviral activity against tobacco mosaic virus (TMV) for the first
      time. The bioassay results showed that most of these compounds exhibited
      excellent in vivo anti-TMV activity, of which 7-methoxycryptopleurine salt
      derivatives 16, 19, and 23 displayed significantly higher activity than 7
      methoxycryptopleurine (1) and commercial ribavirin and ningnanmycin.
      Salification, the most commonly employed method for modifying physical-chemical
      properties, did significantly increase antiviral activity, and different salt
      forms displayed different antiviral effect. This study provides fundamental
      support for development and optimization of phenanthroquinolizidine alkaloids as
      potential inhibitors of plant virus. 

PMID- 24751112
TI  - Depression, diabetic complications and disability among persons with comorbid
      schizophrenia and type 2 diabetes.
AB  - BACKGROUND: People with schizophrenia are at increased risk for type 2 diabetes,
      its complications, depression, and disability. However, little is known about the
      interrelationships of these 3 factors in adults with schizophrenia and type 2
      diabetes. OBJECTIVE: We sought to assess the number of diabetic complications and
      depressive symptom severity as predictors of disability and evaluate depressive
      symptom severity as a mediator of the relationship between diabetic complications
      and disability in a sample of 62 adults with schizophrenia and type 2 diabetes.
      METHODS: Two- and 3-step sequential regression models were used to evaluate the
      relationship of depression and number of diabetic complications with disability.
      Path analysis with bootstrapping was used to evaluate depressive symptom severity
      as a mediator of the relationship between complications and disability. RESULTS:
      Diabetic complications significantly predicted disability scores when controlling
      for age, gender, socioeconomic status, hemoglobin A1C, positive symptom severity,
      and negative symptom severity. The addition of depression severity scores
      resulted in a significant increase in explained variance in disability scores. In
      the final model, only depression severity scores were significantly associated
      with disability scores. The full model accounted for 56.2% of the variance in
      disability scores. Path analysis revealed a significant indirect association of
      diabetic complications to disability through depression severity scores while
      controlling for all covariates. The association between complications and
      disability was nonsignificant when depressive symptom severity was included in
      the model. CONCLUSIONS: Depressive symptoms may present an important and
      tractable target for interventions aimed at reducing disability in people with
      schizophrenia and type 2 diabetes.

PMID- 24751113
TI  - Five-factor model personality traits as predictors of incident coronary heart
      disease in the community: a 10.5-year cohort study based on the Baltimore
      epidemiologic catchment area follow-up study.
AB  - OBJECTIVE: Certain personality and behavioral traits (e.g., type A and type D)
      have been reported to be associated with development and progression of coronary
      heart disease (CHD), but few have examined the relationship using a comprehensive
      assessment of personality along with a structured assessment of psychiatric
      disorders. METHODS: Based on participants (age: 47.3 +/- 12.8; female: 62.6%) of
      the Baltimore Epidemiologic Catchment Area follow-up study, we examined the
      relationship between the 5 major domains of personality traits (neuroticism,
      extraversion, openness, agreeableness, and conscientiousness) and incident CHD
      between Wave III (1993-1996) and Wave IV (2004-2005). RESULTS: Incident CHD
      developed in 65 participants during the follow-up. Those with incident CHD had
      lower on openness (44.06 +/- 9.29 vs. 47.18 +/- 8.80; p = 0.007) and extraversion
      (45.98 +/- 9.25 vs. 49.12 +/- 8.92; p = 0.007) scores than those without.
      Logistic regression models revealed an inverse association (OR = 0.73; 95% CI =
      0.54-0.98) between openness factor z-scores and incident CHD after adjusting for
      putative confounding factors, including DSM III-R Major Depressive Disorder.
      CONCLUSION: High openness appears to be an independent protective factor for
      incident CHD in the community. Future studies should examine behavioral and
      pathophysiologic mechanisms underlying this association.

PMID- 24751114
TI  - What psychiatrists need to know about pacemakers and defibrillators.

PMID- 24751115
TI  - Autoimmune-mediated cognitive impairment: a case report.

PMID- 24751116
TI  - Neuropsychiatric complication of dengue.

PMID- 24751118
TI  - Exploring the effectiveness of a modified comprehensive mind-body intervention
      for medical and psychologic symptom relief.
AB  - BACKGROUND: Chronic illnesses are a major current health concern associated with
      elevated stress and increased health care costs. OBJECTIVE: The objective of this
      study was to describe the preliminary effectiveness of a modified, multimodal 8
      week mind-body intervention on reducing physical and psychological symptoms in
      patients with chronic physical, mental and comorbid health issues. METHODS: Two
      hundred and twenty six adults enrolled in a mind-body group program and completed
      pre and post program assessments (63% completer rate), including the Medical
      Symptoms Checklist (MSCL), Health Promoting Lifestyle Profile (HPLP-II), and
      Symptom Checklist 90R (SCL-90R). RESULTS: Significant improvement was found on 9
      of 23 medical symptoms (p < .002), all health promoting lifestyle behaviors (p <
      .001), and all mental health symptoms (p < .001). CONCLUSIONS: These results
      indicate that a multimodal mind-body intervention might be useful as a
      complementary or adjunct therapy for treatment of chronic medical symptoms.
      Future research is needed to test the intervention using a randomized controlled
      trial.

PMID- 24751117
TI  - Baclofen-induced manic symptoms: case report and systematic review.
AB  - BACKGROUND: The gamma-aminobutyric acid type B receptor agonist baclofen is
      approved for spasticity and is used off-label for diverse types of addictive
      disorders, notably alcohol dependence. Baclofen may induce numerous
      neuropsychiatric adverse drug reactions, including behavioral disinhibition.
      However, this precise adverse drug reaction has never been assessed using either
      a validated causality algorithm or a scale for manic symptoms. METHODS: We report
      a case of a 49-year-old male patient who exhibited de novo mania during treatment
      with baclofen for alcohol dependence. Symptoms were evaluated using the Young
      Mania Rating Scale, and the causality of baclofen was determined using the
      Naranjo algorithm. This case was also compared with other cases of baclofen
      induced mania through a systematic literature review. RESULTS: Mr. X, taking 180
      mg/d of baclofen, presented with mania and scored 24 of 44 on the Young Mania
      Rating Scale, and the imputability of baclofen was "probable" using the Naranjo
      algorithm (8 of 13). In addition, 4 other cases of baclofen-induced mania were
      reported in the literature; 3 cases had a bipolar I disorder history. Baclofen
      induced manic symptoms occurred mostly during the dose-escalation phase.
      CONCLUSION: Baclofen-induced manic symptoms may appear in patients with or
      without bipolar disorder. Particular attention is required during the dose
      increase phase and in patients with a history of mood disorders.

PMID- 24751119
TI  - Creatively caring: effects of arts-based encounters on hospice caregivers in
      South Africa.
AB  - International literature and experience suggest that arts-based encounters can be
      effective in reducing stress and burnout in health care workers. Are these
      principles universal? Are they as applicable and effective in resource
      constrained situations in Africa as in other parts of the world? We describe the
      impact of creative and arts-based encounters on a group of hospice caregivers at
      South Coast Hospice in KwaZulu Natal. An experienced facilitator built a caring
      and trusting relationship with the participants over a three month period through
      a variety of means, including a singing and songwriting intervention specifically
      designed to empower and give voice to the hospice caregivers, most of whom were
      Zulu women. We documented the process through several rounds of interviews,
      extensive field notes, and audio recordings. This article is a reflection on the
      experience and draws from the interviews, correspondence among researchers, field
      notes, and a performance piece written by the facilitator one year after
      completion of the study. We found that the songwriting and other creative
      activities of the engagement provided affirmation and acknowledgment of the
      caregivers as well as an opportunity to release stress, grief, and pain. They
      experienced changes in terms of hope and freedom both for themselves and their
      patients. The conceptual themes that emerged from the interviews with the
      caregivers were interpreted in terms of their inherent cultural assets, a release
      of agency, a sense of revelation, and transformation. The expressive arts can
      have a significantly beneficial effect on hospice workers and their patients, and
      clinical engagement can be enhanced through creative encounters, even in resource
      constrained situations. If such creative processes were to be promoted among a
      wider group of health workers, daily routine work in health care could be not
      just a repetition of well-rehearsed utilitarian rituals but rather a series of
      creative and transformative encounters. 

PMID- 24751120
TI  - Molecular characterization of cryptically circulating rabies virus from ferret
      badgers, Taiwan.
AB  - After the last reported cases of rabies in a human in 1959 and a nonhuman animal
      in 1961, Taiwan was considered free from rabies. However, during 2012-2013, an
      outbreak occurred among ferret badgers in Taiwan. To examine the origin of this
      virus strain, we sequenced 3 complete genomes and acquired multiple rabies virus
      (RABV) nucleoprotein and glycoprotein sequences. Phylogeographic analyses
      demonstrated that the RABV affecting the Taiwan ferret badgers (RABV-TWFB) is a
      distinct lineage within the group of lineages from Asia and that it has been
      differentiated from its closest lineages, China I (including isolates from
      Chinese ferret badgers) and the Philippines, 158-210 years ago. The most recent
      common ancestor of RABV-TWFB originated 91-113 years ago. Our findings indicate
      that RABV could be cryptically circulating in the environment. An understanding
      of the underlying mechanism might shed light on the complex interaction between
      RABV and its host. 

PMID- 24751121
TI  - Experience of a specialist center in the management of anastomotic sinus
      following leaks after low rectal or ileal pouch-anal anastomosis with diverting
      stoma.

PMID- 24751122
TI  - Dangerous cold beverages: a case of swallow syncope.

PMID- 24751123
TI  - A case of multiple misdiagnoses in a septuagenarian.

PMID- 24751124
TI  - Approaches to ascertaining comorbidity information: validation of routine
      hospital episode data with clinician-based case note review.
AB  - BACKGROUND: In clinical practice, research, and increasingly health surveillance,
      planning and costing, there is a need for high quality information to determine
      comorbidity information about patients. Electronic, routinely collected
      healthcare data is capturing increasing amounts of clinical information as part
      of routine care. The aim of this study was to assess the validity of routine
      hospital administrative data to determine comorbidity, as compared with clinician
      based case note review, in a large cohort of patients with chronic kidney
      disease. METHODS: A validation study using record linkage. Routine hospital
      administrative data were compared with clinician-based case note review
      comorbidity data in a cohort of 3219 patients with chronic kidney disease. To
      assess agreement, we calculated prevalence, kappa statistic, sensitivity,
      specificity, positive predictive value and negative predictive value. Subgroup
      analyses were also performed. RESULTS: Median age at index date was 76.3 years,
      44% were male, 67% had stage 3 chronic kidney disease and 31% had at least three
      comorbidities. For most comorbidities, we found a higher prevalence recorded from
      case notes compared with administrative data. The best agreement was found for
      cerebrovascular disease (kappa = 0.80) ischaemic heart disease (kappa = 0.63) and
      diabetes (kappa = 0.65). Hypertension, peripheral vascular disease and dementia
      showed only fair agreement (kappa = 0.28, 0.39, 0.38 respectively) and smoking
      status was found to be poorly recorded in administrative data. The patterns of
      prevalence across subgroups were as expected and for most comorbidities,
      agreement between case note and administrative data was similar. Agreement was
      less, however, in older ages and for those with three or more comorbidities for
      some conditions. CONCLUSIONS: This study demonstrates that hospital
      administrative comorbidity data compared moderately well with case note review
      data for cerebrovascular disease, ischaemic heart disease and diabetes, however
      there was significant under-recording of some other comorbid conditions, and
      particularly common risk factors.

PMID- 24751125
TI  - Accuracy of magnetic resonance imaging for preoperative staging of rectal cancer.
AB  - BACKGROUND: New Zealand has one of the highest rates of rectal adenocarcinoma in
      the world. Magnetic resonance imaging (MRI) is widely used for preoperative
      staging of rectal cancer. The accuracy of MRI varies, which may affect treatment
      decisions. The accuracy of MRI for pretreatment staging of rectal adenocarcinoma
      in a provincial centre in New Zealand has not been investigated. We aimed to
      assess the accuracy of MRI for pretreatment staging of early rectal
      adenocarcinoma in patients managed via the MidCentral Regional Cancer Service
      Multidisciplinary Team. METHODS: A retrospective review of the MidCentral
      Regional Cancer Service Multidisciplinary Team database identified 54 patients
      with rectal adenocarcinoma who proceeded to surgery without preoperative long
      course chemo-radiotherapy. The pretreatment MRI stage was compared with the
      histological stage for each of these patients. RESULTS: MRI correctly staged the
      tumour invasion (T stage) in 24 patients (44% of cases), and lymph node stage in
      38 patients (70% of cases). There was moderate agreement between MRI and
      histological staging for tumour invasion (kappa=0.46) and for lymph node
      involvement (kappa=0.41). Twenty-one cases were under-staged and five cases were
      over-staged with regards to invasion of the muscularis propria. Fourteen cases
      were under-staged, and two cases over-staged in regards to lymph node
      involvement. CONCLUSION: Although MRI provides important pretreatment staging
      information for rectal adenocarcinoma, in our experience MRI is not as accurate
      as in other reports. Multidisciplinary teams managing patients with rectal
      adenocarcinoma should be aware of the limitations of MRI for pretreatment
      staging.

PMID- 24751126
TI  - Babesia venatorum Infection in Child, China.

PMID- 24751127
TI  - A portrait of single and multiple HPV type infections in Brazilian women of
      different age strata with squamous or glandular cervical lesions.
AB  - BACKGROUND: Cervical cancer ranks third in prevalence and fourth as cause of
      death in women worldwide. In Brazil, 17,540 women were diagnosed in 2012 with the
      disease. Persistent infection with high-risk HPV types is a necessary condition
      for the development of pre-invasive and invasive cervical neoplasia. Currently,
      over 100 HPV types have been identified, but HPV16 and 18 are recognized as the
      mayor culprits in cervical carcinogenesis. Our objective was to assess the
      relationships between single- (ST) and multiple-type (MT) HPV infections with
      patients' age and lesion pathological status. METHODS: 328 patients with either
      squamous or glandular intraepithelial or invasive cervical lesion were selected.
      All subjects were tested for HPV genotypes with reverse hybridization for 21 high
      (hr-HPV) and 16 low-risk (lr-HPV) probes. Prevalence of ST and MT HPV infections
      was compared across histological types and age strata. RESULTS: 287 (87%) women
      had at least one HPV type detected and 149 (52%) had MT infections. The most
      prevalent HPV type was HPV16, present in 142 cases (49% of all HPV-positive
      cases), followed by HPV58, 52, 31, 35 and 33. HPV18, in single or multiple
      infections, occurred in 23 cases (8% of hr-HPV cases). Almost all glandular
      lesions were associated with HPV16 and 18 alone. Multiple infections were
      significantly more prevalent in squamous than in glandular lesion for HPV16 and
      18 (P = 0.04 and 0.03 respectively). The prevalence of MT infections followed a
      bimodal distribution; peaking in women younger 29 years and in those aged 50 to
      59. CONCLUSIONS: Our data indicate that prevention strategies for pre-invasive
      and invasive squamous lesions should be focused on HPV16 and a few alpha-9 HPV
      types. It is clear to us that in young women, prophylaxis must cover a large
      amalgam of HPV types beyond classic HPV16 and 18.

PMID- 24751128
TI  - Patellins 3 and 6, two members of the Plant Patellin family, interact with the
      movement protein of Alfalfa mosaic virus and interfere with viral movement.
AB  - Movement proteins (MPs) encoded by plant viruses interact with host proteins to
      facilitate or interfere with intra- and/or intercellular viral movement. Using
      yeast two-hybrid and bimolecular fluorescence complementation assays, we herein
      present in vivo evidence for the interaction between Alfalfa mosaic virus (AMV)
      MP and Arabidopsis Patellin 3 (atPATL3) and Patellin 6 (atPATL6), two proteins
      containing a Sec14 domain. Proteins with Sec14 domains are implicated in membrane
      trafficking, cytoskeleton dynamics, lipid metabolism and lipid-mediated
      regulatory functions. Interestingly, the overexpression of atPATL3 and/or atPATL6
      interfered with the plasmodesmata targeting of AMV MP and correlated with reduced
      infection foci size. Consistently, the viral RNA levels increased in the single
      and double Arabidopsis knockout mutants for atPATL3 and atPATL6. Our results
      indicate that, in general, MP-PATL interactions interfere with the correct
      subcellular targeting of MP, thus rendering the intracellular transport of viral
      MP-containing complexes less efficient and diminishing cell-to-cell movement. 

PMID- 24751129
TI  - Genetic variation in niche construction: a comment on Saltz and Nuzhdin.

PMID- 24751130
TI  - Limited damage of tissue mimic caused by a collapsing bubble under low-frequency
      ultrasound exposure.
AB  - In this study, we investigated the bubble induced serious damage to tissue mimic
      exposed to 27-kHz ultrasound. The initial bubble radius ranged from 80 to 100
      MUm, which corresponded approximately to the experimentally-evaluated resonant
      radius of the given ultrasound frequency. The tissue mimic consisted of 10 wt%
      gelatine gel covered with cultured canine kidney epithelial cells. The collapsing
      bubble behaviour during the ultrasound exposure with negative peak pressures of
      several hundred kPa was captured by a high-speed camera system. After ultrasound
      exposure, a cell viability test was conducted based on microscopic bright-field
      images and fluorescence images for living and dead cells. In the viability test,
      cells played a role in indicating the damaged area. The bubble oscillations
      killed the cells, and on occasion detached layers of cultured cells from the gel.
      The damaged area was comparable or slightly larger than the initial bubble size,
      and smaller than the maximum bubble size. We concluded that only a small area in
      close proximity to the bubble could be damaged even above transient cavitation
      threshold.

PMID- 24751132
TI  - The AJT report.

PMID- 24751131
TI  - Maternal positioning to rotate fetuses in occiput posterior position in labor.

PMID- 24751135
TI  - Skin nodule on the ear of a kidney-pancreas transplant recipient.

PMID- 24751136
TI  - Are human male patients with DAX1/NR0B1 mutations infertile?
AB  - DAX-1 stands for Dosage sensitive sex-reversal, Adrenal hypoplasia congenital
      (AHC), on the X chromosome. DAX-1 mutations usually cause primary adrenal
      insufficiency or congenital adrenal hypoplasia in early childhood and
      hypogonadotropic hypogonadism (MIM # 300200). DAX-1 protein is necessary to
      maintain normal spermatogenesis. In humans, male fertility has been studied in
      few patients carrying DAX-1 mutations. Cases of azoospermia have been reported,
      as well as unsuccessful gonadotropin treatments. The clinician should be informed
      that TESE-ICSI technique carries a potential hope to father non-affected
      children, as shown in this review. 

PMID- 24751138
TI  - Structure-activity relationships for a series of compounds that inhibit
      aggregation of the Alzheimer's peptide, Abeta42.
AB  - Inhibiting aggregation of the amyloid-beta (Abeta) peptide may be an effective
      strategy for combating Alzheimer's disease. As the high-resolution structure of
      the toxic Abeta aggregate is unknown, rational design of small molecule
      inhibitors is not possible, and inhibitors are best isolated by high-throughput
      screening. We applied high-throughput screening to a collection of 65,000
      compounds to identify compound D737 as an inhibitor of Abeta aggregation. D737
      diminished the formation of oligomers and fibrils, and reduced Abeta42-induced
      cytotoxicity. Most importantly, D737 increased the life span and locomotive
      ability of transgenic flies in a Drosophila melanogaster model of Alzheimer's
      disease (J Biol Chem, 287, 2012, 38992). To explore the chemical features that
      make D737 an effective inhibitor of Abeta42 aggregation and toxicity, we tested a
      small collection of eleven analogues of D737. Overall, the ability of a compound
      to inhibit Abeta aggregation was a good predictor of its efficacy in prolonging
      the life span and locomotive ability of transgenic flies expressing human Abeta42
      in the central nervous system. Two compounds (D744 and D830) with fluorine
      substitutions on an aromatic ring were effective inhibitors of Abeta42
      aggregation and increased the longevity of transgenic flies beyond that observed
      for the parent compound, D737.

PMID- 24751139
TI  - Baseline immunity to diphtheria and immunologic response after booster
      vaccination with reduced diphtheria and tetanus toxoid vaccine in Thai health
      care workers.
AB  - A prospective study to evaluate immune status against diphtheria and immunologic
      response after tetanus-diphtheria (Td) booster vaccination was conducted in 250
      Thai health care workers (HCWs). A protective antibody was found in 89.2% of the
      HCWs (95% confidence interval [CI], 83.3%-91.5%) before receipt of the Td booster
      vaccination, compared with 97.2% (95% CI, 95.1%-99.3%) after receipt of the first
      dose of booster (P < .001). The mean antibody level against diphtheria increased
      from 0.39 IU/mL (95% CI, 0.35-0.44 IU/mL) before the Td booster vaccination to
      1.20 IU/mL (95% CI, 1.12-1.29 IU/mL) after the vaccination (P < .001). Td booster
      vaccination should be considered for Thai HCWs to maintain immunity against
      diphtheria, which still circulates in Thailand. 

PMID- 24751140
TI  - Hygiene behavior in persons with type 2 diabetes.

PMID- 24751137
TI  - Global transcriptional analysis reveals surface remodeling of Anaplasma marginale
      in the tick vector.
AB  - BACKGROUND: Pathogens dependent upon vectors for transmission to new hosts
      undergo environment specific changes in gene transcription dependent on whether
      they are replicating in the vector or the mammalian host. Differential gene
      transcription, especially of potential vaccine candidates, is of interest in
      Anaplasma marginale, the tick-borne causative agent of bovine anaplasmosis.
      METHODS: RNA-seq technology allowed a comprehensive analysis of the
      transcriptional status of A. marginale genes in two conditions: bovine host blood
      and tick derived cell culture, a model for the tick vector. Quantitative PCR was
      used to assess transcription of a set of genes in A. marginale infected tick
      midguts and salivary glands at two time points during the transmission cycle.
      RESULTS: Genes belonging to fourteen pathways or component groups were found to
      be differentially transcribed in A. marginale in the bovine host versus the tick
      vector. One of the most significantly altered groups was composed of surface
      proteins. Of the 56 genes included in the surface protein group, eight were up
      regulated and 26 were down regulated. The down regulated surface protein encoding
      genes include several that are well studied due to their immunogenicity and
      function. Quantitative PCR of a set of genes demonstrated that transcription in
      tick cell culture most closely approximates transcription in salivary glands of
      recently infected ticks. CONCLUSIONS: The ISE6 tick cell culture line is an
      acceptable model for early infection in tick salivary glands, and reveals
      disproportionate down regulation of surface protein genes in the tick.
      Transcriptional profiling in other cell lines may help us simulate additional
      microenvironments. Understanding vector-specific alteration of gene
      transcription, especially of surface protein encoding genes, may aid in the
      development of vaccines or transmission blocking therapies.

PMID- 24751141
TI  - Clostridium difficile in a children's hospital: assessment of environmental
      contamination.
AB  - Clostridium difficile infection (CDI) is the most frequent infectious cause of
      health care-associated diarrhea. Three cases of CDI, in children age 2, 3, and 14
      years, occurred in the hematology/oncology ward of our children's hospital over
      48 hours. We aimed to assess environmental contamination with C difficile in the
      shared areas of this unit, and to determine whether person-to-person transmission
      occurred. C difficile was recovered from 5 of 18 samples (28%). We compared C
      difficile isolated from each patient and the environment using pulsed-field gel
      electrophoresis, and found that none of the patient strains matched any of the
      others, and that none matched any strains recovered from the environment,
      suggesting that person-to-person transmission had not occurred. We found that C
      difficile was prevalent in the environment throughout shared areas of the
      children's hospital unit. Molecular typing to identify mechanisms of transmission
      is useful for devising appropriate interventions. 

PMID- 24751142
TI  - Persistence and complex evolution of fluoroquinolone-resistant Streptococcus
      pneumoniae clone.
AB  - Prolonged outbreaks of multidrug-resistant Streptococcus pneumoniae in health
      care facilities are uncommon. We found persistent transmission of a
      fluroquinolone-resistant S. pneumoniae clone during 2006-2011 in a post-acute
      care facility in Israel, despite mandatory vaccination and fluoroquinolone
      restriction. Capsular switch and multiple antimicrobial nonsusceptibility
      mutations occurred within this single clone. The persistent transmission of
      fluoroquinolone-resistant S. pneumoniae during a 5-year period underscores the
      importance of long-term care facilities as potential reservoirs of multidrug
      resistant streptococci. 

PMID- 24751143
TI  - Multi-residue analysis of pharmaceuticals in wastewater by liquid chromatography
      magnetic sector mass spectrometry: method quality assessment and application in a
      Belgian case study.
AB  - Through systematic research a novel analytical method using solid-phase
      extraction (SPE) and liquid chromatography magnetic sector mass spectrometry was
      developed for the measurement of 43 pharmaceuticals in wastewater. A thorough
      method validation quantified the contribution of both the extraction recovery and
      matrix effects in the overall method process efficiency, and a detailed
      uncertainty analysis was performed to elaborate a quality labelling strategy to
      be used in data interpretation. Compounds for which a precise (relative standard
      deviation<20%) process efficiency between 60% and 140% was determined, were
      labelled as 'quantitative' whereas the results for other compounds should be
      interpreted as 'indicative'. Method application on influent and effluent samples
      of (i) a conventional active sludge system and (ii) a parallel membrane
      bioreactor/conventional active sludge wastewater treatment plant in Belgium
      revealed the occurrence of 22 pharmaceuticals. The anti-inflammatory drug
      diclofenac and the antidepressant venlafaxine were measured in the effluents at
      concentrations ranging from 0.5 to 1.8 MUg L(-1) and 0.2 to 0.5 MUg L(-1),
      respectively, which indicated to be of high potential environmental risk for the
      receiving river Dender, Belgium.

PMID- 24751144
TI  - Knocking down CDK4 mediates the elevation of let-7c suppressing cell growth in
      nasopharyngeal carcinoma.
AB  - BACKGROUND: CDK4 is a protein kinase in the CDK family important for G1/S phase
      cell cycle progression. However, the roles and molecular mechanisms of CDK4
      triggering nasopharynx carcinogenesis are still unclear. METHODS: Lentiviral
      vector mediated shRNA was used to suppress CDK4 expression and examine its
      molecular mechanisms. Using immunohistochemistry, we analyzed CDK4 protein
      expression in clinicopathologically characterized nasopharyngeal carcinoma (NPC)
      cases and nasopharyngeal tissues (NPs). Survival curves were plotted by the
      Kaplan-Meier method and compared using the log-rank test. RESULTS: In this
      investigation, we knocked down CDK4 expression and observed that NPC cell growth
      and cell cycle progression were significantly blocked by suppressing expression
      of CCND1, CDK6, and E2F1 as well as elevated p21 expression. Further, we found
      that reduced CDK4 expression elevated the expression of let-7c, a tumor
      suppressive miRNA modulated by E2F1. We found that let-7c was markedly
      downregulated in NPC tissues compared to NPs and suppressed cell growth and cell
      cycle progression by modulating p15/p16/CDK4/E2F1 pathway. Finally, CDK4 protein
      was observed to be overexpressed in NPC tissues and could be considered an
      unfavorable prognosis factor for NPC patients although its independent prognostic
      value did not reach statistical significance (p = 0.087). CONCLUSIONS: Our
      results demonstrated that overexpressed CDK4 is an unfavorable prognostic factor
      which suppresses the expression of tumor suppressive-factor let-7c through
      p21/CCND1/CDK6/E2F1 signaling, and inhibits cell proliferation by
      p15/p16/CDK4/E2F1 feedback signaling in NPC.

PMID- 24751145
TI  - Spatially heterogeneous corneal mechanical responses before and after riboflavin
      ultraviolet-A crosslinking.
AB  - PURPOSE: To determine the heterogeneous through-thickness strains in the cornea
      at physiologic intraocular pressures before and after corneal collagen
      crosslinking (CXL) using noninvasive ultrasound. SETTING: Department of
      Biomedical Engineering, Ohio State University, Columbus, Ohio, USA. DESIGN:
      Experimental study. METHODS: Sixteen paired canine corneoscleral shells were
      divided into 2 groups. The CXL group completed a standard CXL protocol using
      riboflavin-ultraviolet-A (UVA) irradiation. The control group was given an
      identical treatment except UVA irradiation. Ultrasound scans (at 55 MHz) of the
      cornea were obtained before and after treatment as the corneoscleral shell was
      inflated from 5 mm Hg to 45 mm Hg to calculate the distributive through-thickness
      strains in the cornea. The mean radial and tangential strains of the whole cornea
      layer, as well as those of the anterior, middle, and posterior thirds of the
      cornea, were compared before and after treatment in the control group and CXL
      group using linear mixed models with repeated measures. RESULTS: Significant
      reductions in tangential and radial strains occurred in the CXL group (P=.003 and
      P=.0025, respectively) but not the control group (P=.08 and P=.63, respectively).
      The anterior third had the smallest strains in all pretreated corneas (P<.001)
      and posttreated corneas (CXL group, P=.023; control group, P=.01). CONCLUSIONS:
      Ultrasound speckle tracking showed heterogeneous strain distributions through the
      cornea and confirmed that CXL results in a stiffer corneal response (ie, smaller
      strains during physiologic loadings). This technique may provide a clinical tool
      to quantify the biomechanical effects of CXL. FINANCIAL DISCLOSURE: No author has
      a financial or proprietary interest in any material or method mentioned.

PMID- 24751146
TI  - Corneal biomechanical effects: small-incision lenticule extraction versus
      femtosecond laser-assisted laser in situ keratomileusis.
AB  - PURPOSE: To compare the biomechanical properties of the cornea after small
      incision lenticule extraction (lenticule extraction group) with those after
      femtosecond laser-assisted laser in situ keratomileusis (femtosecond LASIK
      group). SETTING: Tianjin Eye Hospital & Eye Institute, Tianjin Key Laboratory of
      Ophthalmology and Visual Science, Tianjin Medical University, Tianjin, China.
      DESIGN: Prospective comparative case series. METHODS: Corneal hysteresis (CH),
      the corneal resistance factor (CRF), and 37 other biomechanical waveform
      parameters were quantitatively assessed with the Ocular Response Analyzer
      preoperatively and 1 week and 1, 3, and 6 months postoperatively. RESULTS: Each
      group comprised 40 eyes. The decrease in CH and the CRF was statistically
      significant 1 week postoperatively compared with preoperatively in both groups
      (P<.0001). However, the CH and CRF values in the lenticule extraction group were
      significantly higher than those in the femtosecond LASIK group 3 months and 6
      months postoperatively (P<.032). The residual stromal thickness index versus the
      CRF and CH and the planned lenticule thickness versus the change in central
      corneal thickness were statistically significant in the lenticule extraction
      group (r = 0.388 to 0.950, P<.018); no significant correlation was found in the
      femtosecond LASIK group. In the waveform analysis of the lenticule extraction
      group, 28 of the 37 biomechanical waveform parameters differed significantly
      between preoperative values and postoperative values (P<.035). CONCLUSIONS: Both
      small-incision lenticule extraction and femtosecond laser-assisted LASIK can
      cause biomechanical changes in the cornea. However, changes in the cornea's
      viscoelastic properties were less after lenticule extraction than after LASIK.
      FINANCIAL DISCLOSURE: No author has a financial or proprietary interest in any
      material or method mentioned.

PMID- 24751147
TI  - Placental and cord insertion pathologies: screening, diagnosis, and management.
AB  - Placenta previa, low-lying placenta, and placenta accreta are aberrations in the
      normal development of the placenta. Diagnosis in the prenatal period is essential
      because each of these pathologies can have a profound impact on the management of
      labor, birth, and the third stage. In recent years, there has been an increase in
      the occurrence of these placental abnormalities, with the increase in the
      cesarean rate considered to be a main cause of this phenomenon. Comprehensive
      risk assessment, combined with recent advances in ultrasonography, can provide
      earlier detection of impaired placental implantation. Umbilical cord insertion
      pathologies are also of concern. Velamentous cord insertion is a defect in the
      insertion site of the umbilical cord resulting from the atrophy of portions of
      the developing placenta. In this condition, the blood vessels of the umbilical
      cord are not protected by Wharton's jelly, resulting in a potential for increased
      risk of breakage when the amniotic membranes rupture. Vasa previa is a
      velamentous insertion of the umbilical cord in which the blood vessels are
      present over the cervical os. If these blood vessels rupture during labor, it can
      have catastrophic effects on the fetus. Prenatal diagnosis of this condition can
      allow the certified nurse-midwife/certified midwife (CNM/CM) to plan for the safe
      birth of the newborn and avoid fetal hemorrhage. This article provides a review
      of risk factors, diagnosis pathophysiology, and management options for these
      conditions, thus enabling the CNM/CM to provide safe, effective care and
      management. 

PMID- 24751149
TI  - Staphylococcus aureus carrying mecC gene in animals and urban wastewater, Spain.

PMID- 24751148
TI  - Intrathecal antagonism of microglial TLR4 reduces inflammatory damage to blood
      spinal cord barrier following ischemia/reperfusion injury in rats.
AB  - BACKGROUND: Inflammatory reaction in blood-spinal cord barrier (BSCB) plays a
      crucial role in ischemia/reperfusion (I/R) injury. It has been shown that
      microglia could be activated through Toll-like receptors (TLRs). Therefore, we
      hypothesize that TLR4 is involved in the microglial activation and BSCB
      disruption after I/R. RESULTS: To verify our hypothesis, we analyzed the
      behavioral data, changes of BSCB permeability, as well as expressions of
      microglial marker Iba-1 and TLR4 in spinal cord I/R model induced by 14 min
      aortic occlusion. Double immunostaining reveals that after I/R, Iba-1
      immunoreactivity increased gradually 12 h after reperfusion and maintained at a
      such level throughout 36 h. Such increasing pattern of Iba-1 expression is
      consistent with the increases in Evan's Blue (EB) extravasation, spinal water
      content and mechanical allodynia demonstrated by lowed withdrawal threshold to
      Von Frey filaments. Moreover, double immunostaining suggested that TLR4 was
      highly expressed in microglia. Intrathecal infusion of minocycline and TAK-242
      (TLR4 inhibitor) treatment attenuated I/R-induced allodynia and BSCB leakage. In
      contrast, LPS induced TLR4 expression aggregated above-mentioned injuries.
      Furthermore, the nuclear factor-kappa B (NF-kappaB) activity has a similar
      profile as TLR4 activity. It is consisted with the results of NF-kappaB mRNA and
      protein expression changes and activation of downstream cytokine, IL-1beta.
      Expectedly, intrathecal infusion of pyrrolidine dithiocarbamate (PDTC), a NF
      kappaB inhibitor, showed similar protective effects as minocycline and TAK-242.
      In addition, our data show that TLR4 closely involved in I/R-induced inflammatory
      damage induced neuronal apoptosis. Significantly, neutralizing TLR4 function
      largely reduced neuronal apoptosis determined by NeuN immunoreactivity in ventral
      gray matter and increased percentage of double-label cells with cleaved caspase3,
      whereas LPS reversed these effects. Similarly, inhibitions of microglia and NF
      kappaB with minocycline or PDTC treatment accordingly perform the same protective
      effects on I/R injury. CONCLUSION: The results indicate that compromised BSCB
      caused by I/R injury lead to spinal microglial activation and TLR4, its membrane
      bound receptor, up-regulation, which then initiate neuro-inflammation and neuro
      apoptosis via NF-kappaB/ IL-1beta pathway. To inhibit the positive feedback loop
      of TLR4-microglia-NF-kappaB/ IL-1beta pathway by minocycline, TAK-242 (TLR4
      inhibitor) and pyrrolidine dithiocarbamate (PDTC, NF-kappaB inhibitor) may
      provide new targets for treating I/R injury in clinic.

PMID- 24751150
TI  - First-in-human study of the safety and efficacy of TOL101 induction to prevent
      kidney transplant rejection.
AB  - TOL101 is a murine IgM mAb targeting the alphabeta TCR. Unlike other T cell
      targets, the alphabeta TCR has no known intracellular signaling domains and may
      provide a nonmitogenic target for T cell inactivation. We report the 6-month
      Phase 2 trial data testing TOL101 in kidney transplantation. The study was
      designed to identify a dose that resulted in significant CD3 T cell modulation
      (<25 T cell/mm(3) ), to examine the safety and tolerability of TOL101 and to
      obtain preliminary efficacy information. Thirty-six patients were enrolled and
      given 5-10 daily doses of TOL101; 33 patients completed dosing, while three
      discontinued after two doses due to a self-limiting urticarial rash. Infusion
      adjustments, antihistamines, steroids and dose escalation of TOL101 reduced the
      incidence of the rash. Doses of TOL101 above 28 mg resulted in prolonged CD3
      modulation, with rapid recovery observed 7 days after therapy cessation. There
      were no cases of patient or graft loss. Few significant adverse events were
      reported, with one nosocomial pneumonia. There were five biopsy-confirmed acute
      cellular rejections (13.9%); however, no donor-specific antibodies were detected.
      Overall TOL101 was well-tolerated, supporting continued clinical development
      using the dose escalating 21-28-42-42-42 mg regimen.

PMID- 24751151
TI  - Prevalence and molecular characteristics of methicillin-resistant Staphylococcus
      aureus (MRSA) in organic pig herds in The Netherlands.
AB  - The prevalence of the methicillin-resistant Staphylococcus aureus (MRSA) among
      conventional pig herds in the Netherlands is high (around 71%). Nevertheless,
      information about the prevalence of MRSA among organic pig herds is lacking.
      Here, we report a study on 24 of the 49 organic pig herds in the Netherlands. The
      prevalence of MRSA positive herds showed to be 21%. The genetic characteristics
      of the MRSA isolates were similar to MRSA CC398 described in conventional pigs
      except one exceptional HA-MRSA CC30 found in one herd, which was presumably
      caused by human to animal transmission. This resulted in a prevalence of MRSA
      CC398 in the organic herds of 16.7%. 

PMID- 24751152
TI  - The safety and efficacy of mediastinoscopy when performed by general thoracic
      surgeons.
AB  - BACKGROUND: Previous publications suggest that mediastinoscopy only obtains a
      biopsy of lymph node tissue in about 50% of patients; however, those data
      included results from nonthoracic surgeons. METHODS: A retrospective cohort study
      was performed using a database of a consecutive series of patients who underwent
      mediastinoscopy or video mediastinoscopy by general thoracic surgeons only.
      RESULTS: Between January 1997 and September 2013, 1,970 patients underwent
      mediastinoscopy (video mediastinoscopy in the last 243). The indications were
      staging for known or suspected lung cancer in 68.5%. Morbidity occurred in 25
      patients (1.3%). Significant bleeding occurred in 5 patients (0.25%): 2 patients
      required sternotomy, and bleeding in the other 3 was controlled with packing
      alone. No patients required transfusion. There were no 30-day operative deaths.
      Median operative time was 18 minutes, and 96.1% of operations were performed as
      outpatient procedures. Lymph node tissue was obtained from all patients, and
      biopsy specimens from at least two mediastinal stations were obtained for 98% who
      had non-small cell lung cancer. The false-negative rate for N2 lymph nodes that
      were accessible by mediastinoscopy was 8.2% when lymph nodes dissected at the
      time of pulmonary resection were used as the reference standard. CONCLUSIONS: In
      the hands of general thoracic surgeons mediastinoscopy provides lymph node tissue
      from multiple stations essentially 100% of the time; has minimal morbidity and
      essentially no deaths; and is a short outpatient procedure. Specialty-specific
      data (and not national databases) should be used when the efficacy of
      mediastinoscopy is compared with endobronchial ultrasound.

PMID- 24751153
TI  - Contemporary results of surgical repair of recurrent aortic arch obstruction.
AB  - BACKGROUND: There is a paucity of data on the current outcomes of surgical
      intervention for recurrent aortic arch obstruction (RAAO) after initial aortic
      arch repair in children. The goal of this study is to report the long-term
      results in these patients. METHODS: All patients undergoing surgical intervention
      for RAAO at Texas Children's Hospital from 1995 to 2012 were included. The cohort
      was divided into four groups based on initial procedure: (1) simple coarctation
      repair, (2) Norwood procedure, (3) complex congenital heart disease, and (4)
      interrupted aortic arch. RESULTS: A total of 48 patients age 9 months (range, 22
      days to 36 years) underwent 49 procedures for RAAO. All patients had an anatomic
      repair consisting of either patch aortoplasty (n=27, 55%), aortic arch
      advancement (n=8, 16%), sliding arch aortoplasty (n=6, 12%), placement of an
      interposition graft (n=2, 17%), reconstruction with donor allograft (n=4, 8%),
      extended end-to-end anastomosis (n=1, 2%), or redo Norwood-type reconstruction
      (n=1, 2%). Most procedures (n=46, 94%) were performed through a median sternotomy
      using cardiopulmonary bypass. At a median follow-up of 6.1 years (range, 9 days
      to 17 years), only 2 patients required surgical or catheter-based intervention
      for RAAO. Hypertension was present in 10% of patients at last follow-up. There
      were no neurologic or renal complications. There was 1 perioperative death after
      an aortic arch advancement in group 1. Four other patients have died during
      follow-up, none of the deaths related to RAAO. CONCLUSIONS: Anatomic repair of
      RAAO is a safe procedure associated with low morbidity and mortality, and low
      long-term reintervention rates.

PMID- 24751154
TI  - Influence of diabetes mellitus on long-term clinical and economic outcomes after
      coronary artery bypass grafting.
AB  - BACKGROUND: China has the most patients with diabetes mellitus (DM) in the world
      and, annually, approximately 1 million Chinese become diabetic. We investigated
      both clinical and economic outcomes in a large Chinese cohort of diabetic
      patients undergoing coronary artery bypass graft surgery (CABG). METHODS: All
      9,240 consecutive patients who underwent isolated, primary, elective CABG between
      January 1999 and December 2008 were included and analyzed for long-term major
      adverse cardiovascular and cerebrovascular events and economic outcomes up to 2
      years after the procedure. The DM patients were divided into DM subgroups
      controlled by diet (n = 375), medication (n = 1,826) or insulin (n = 481).
      RESULTS: During the study period, the proportion of patients undergoing CABG who
      have DM increased from 20.1% to 31.8% in China. None of the DM subgroups was
      independently associated with in-hospital death, but DM was an independent
      predictor for long-term major adverse cardiovascular and cerebrovascular events
      (hazard ratio 1.29, 95% confidence interval: 1.14 to 1.46). Medically controlled
      DM and insulin-dependent DM, but not diet-controlled DM were independent
      predictors of long-term outcomes after CABG. Cost for initial hospitalization was
      higher for DM patients (76,782 Ren Min Bi [RMB] versus 65,521 RMB, respectively;
      p < 0.001). At 2 years after CABG, costs for DM patients were 11,261 RMB
      (approximately US $1,623) higher than for non-DM patients (p < 0.001).
      CONCLUSIONS: CABG for patients with DM was significantly more expensive and was
      associated with worse long-term outcomes compared with non-DM patients. The
      rising incidence of DM, combined with the significant incremental costs
      represents significant clinical, economic, and social challenges for the Chinese
      healthcare system.

PMID- 24751155
TI  - Comparison of pyloric intervention strategies at the time of esophagectomy: is
      more better?
AB  - BACKGROUND: Controversy remains regarding the role of pyloric drainage procedures
      after esophagectomy with gastric conduit reconstruction. We aimed to compare the
      effect of pyloric drainage strategies upon subsequent risk of complications
      suggestive of conduit distention, including aspiration and anastomotic leak.
      METHODS: A retrospective study was conducted reviewing patients undergoing
      esophagectomy between January 2007 and April 2012. Prospectively collected data
      included baseline comorbidities, operative details, hospital course, and
      complications. Statistical comparisons were performed using analysis of variance
      for continuous variables and chi(2) testing for categorical variables. RESULTS:
      There were 361 esophagectomies performed during the study period; 68 were
      excluded from analysis (for prior esophagogastric surgery or benign disease or
      both). Among 293 esophagectomies included, emptying procedures were performed as
      follows: 44 (15%), no drainage procedure; 197 (67%), pyloromyotomy/pyloroplasty;
      8 (3%), dilation alone; 44 (15%), dilation plus onabotulinumtoxinA. Aspiration
      occurred more frequently when no pyloric intervention was performed (5 of 44
      [11.4%] versus 6 of 249 [2.4%], p = 0.030). The incidences of anastomotic leak
      (18 [6.1%]) and gastric outlet obstruction (5 [1.7%]) were statistically similar
      among groups. Subgroup analysis demonstrated persistence of these findings when
      limiting the comparison to transthoracic esophagectomies. Major complications
      directly related to pyloroplasty/pyloromyotomy occurred in 2 patients (0.6%),
      including 1 death (0.3%). CONCLUSIONS: These data suggest that omission of
      pyloric intervention at the index operation results in more frequent aspiration
      events. The combination of dilation plus onabotulinumtoxinA provided for a
      similar complication profile compared with surgical drainage. Future prospective
      comparisons are needed to evaluate these short-term effects of pyloric
      intervention as well as long-term sequelae such as dumping syndrome and bile
      reflux.

PMID- 24751156
TI  - Carriage rate and effects of vaccination after outbreaks of serogroup C
      meningococcal disease, Brazil, 2010.
AB  - During 2010, outbreaks of serogroup C meningococcal (MenC) disease occurred in 2
      oil refineries in Sao Paulo State, Brazil, leading to mass vaccination of
      employees at 1 refinery with a meningococcal polysaccharide A/C vaccine. A cross
      sectional study was conducted to assess the prevalence of meningococci carriage
      among workers at both refineries and to investigate the effect of vaccination on
      and the risk factors for pharyngeal carriage of meningococci. Among the
      vaccinated and nonvaccinated workers, rates of overall meningococci carriage
      (21.4% and 21.6%, respectively) and of MenC carriage (6.3% and 4.9%,
      respectively) were similar. However, a MenC strain belonging to the sequence
      type103 complex predominated and was responsible for the increased incidence of
      meningococcal disease in Brazil. A low education level was associated with higher
      risk of meningococci carriage. Polysaccharide vaccination did not affect carriage
      or interrupt transmission of the epidemic strain. These findings will help inform
      future vaccination strategies. 

PMID- 24751157
TI  - Design, synthesis and biological evaluation of peptidyl epoxyketone proteasome
      inhibitors composed of beta-amino acids.
AB  - A series of novel di- and tripeptidyl epoxyketone derivatives composed of beta
      amino acids were designed, synthesized and evaluated for their proteasome
      inhibitory activities and anti-proliferation activities against two multiple
      myeloma cell lines RPMI 8226 and NCI-H929 and normal cells (peripheral blood
      mononucleated cells). Among these tested compounds, tripeptidyl analogues showed
      much more potent activities than dipeptides, and four tripeptidyl compounds
      exhibited proteasome inhibitory activities with IC50 values ranging from 0.97 +/-
      0.05 to 1.85 +/- 0.11 MUM. In addition, all the four compounds showed anti
      proliferation activities with IC50 values at low micromolar levels against two
      multiple myeloma cell lines and weak activities against normal cells.
      Furthermore, Western blot analysis was performed to verify the proteasome
      inhibition induced by compounds 21d and 21e. All the experimental results
      validated that the beta-amino acid building block has the potential for the
      development of proteasome inhibitors.

PMID- 24751158
TI  - Developmental toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin in artificially
      fertilized crucian carp (Carassius auratus) embryo.
AB  - 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a persistent bioaccumulative
      environmental contaminant that is an endocrine disruptor. Embryos of various fish
      species are responsive to TCDD and have been used as an alternative method to the
      acute toxicity test with juvenile and adult fish. The TCDD test has similar
      endpoints of developmental toxicity. However, their sensitivity and signs of TCDD
      induced toxicity are different depending on fish species and its habit. Crucian
      carp (Carassius auratus) - the sentinel species for persistent organic pollutants
      and a common foodfish in China, Japan, and Korea - was used to identify the
      developmental toxicity of TCDD. We obtained the fertilized eggs from the
      artificial fertilization of crucian carp (97.45% success rate). Embryos at 3h
      post fertilization (hpf) were exposed to no vehicle, vehicle (dimethylsulfoxide,
      0.1% v/v) or TCDD (0.128, 0.32, 0.8, 2 and 5 MUg/L) for 1h and then fresh water
      was changed and aerated. Embryonic development and toxicity were monitored until
      150 hpf. TCDD-exposed group showed no effects on embryo mortality and hatching
      rate from 6 to 126 hpf. On the other hand, the post-hatching mortality rate in
      TCDD-exposed group was increased in a dose-dependent manner, especially at high
      doses (0.8, 2 and 5 MUg/L). The LD50 for larval mortality was calculated to 0.24
      ng TCDD/g embryo. Pericardial edema was continuously observed in larvae of TCDD
      exposed groups from hatching complete time (78 hpf), followed by the onset of
      yolk sac edema. Hemorrhage and edema showed a significant increase depending on
      exposure concentration and time. Expression of TCDD-related CYP1A genes was
      evaluated quantitatively. Embryo and larvae in TCDD-exposed groups displayed a
      significant increase of CYP1A gene expression. Overall, we defined TCDD-induced
      toxicity in artificially fertilized crucian carp embryo and these results suggest
      that crucian carp can be applied as an early life stage model of TCDD-induced
      toxicity.

PMID- 24751160
TI  - Epigallocatechin gallate promotes the development of mouse 2-cell embryos in
      vitro by regulating mitochondrial activity and expression of genes related to p53
      signalling pathway.
AB  - Preliminary studies have found that the epigallocatechin gallate (EGCG) at proper
      concentration could promote development of pre-implantation mouse embryos in
      vitro. However, the underlying mechanisms have not been well understood. In this
      study, we collected 1-cell embryos from Kunming (KM) mice, cultured them in M16
      medium or M16 medium supplemented with 10 MUg/mL EGCG and investigated the
      effects of EGCG on mitochondrial activity and reactive oxygen species (ROS) level
      of 2-cell embryos. Furthermore, we explored expression differences of genes
      related to p53 signalling pathway in 2-cell embryos using a PCR array. The
      results showed that ROS level and mitochondrial membrane potential were
      significantly lower in embryos cultured in the EGCG group than in the M16 group
      (p < 0.05), while the adenosine triphosphate content was slightly lower than in
      the M16 group (p > 0.05). PCR array test results showed that 18 genes were
      differentially expressed, among which eight genes involving cell growth, cell
      cycle regulation and mRNA transcription were up-regulated and 10 genes involving
      apoptosis, cell cycle arrest and DNA repair were down-regulated in the EGCG
      groups. It is concluded that EGCG could promote the development of 1-cell embryos
      in vitro possibly due to its ability to scavenge ROS and regulate mitochondrial
      activity. In addition, EGCG could influence expression of genes related to p53
      signalling pathway in 2-cell embryos and promote cell cycle progression. 

PMID- 24751159
TI  - Exercise therapy in adults with serious mental illness: a systematic review and
      meta-analysis.
AB  - BACKGROUND: Individuals with serious mental illness are at a higher risk of
      physical ill health. Mortality rates are at least twice those of the general
      population with higher levels of cardiovascular disease, metabolic disease,
      diabetes, and respiratory illness. Although genetics may have a role in the
      physical health problems of these patients, lifestyle and environmental factors
      such as levels of smoking, obesity, poor diet, and low levels of physical
      activity also play a prominent part. METHODS: We conducted a systematic review
      and meta-analysis of randomised controlled trials comparing the effect of
      exercise interventions on individuals with serious mental illness.Searches were
      made in Ovid MEDLINE, Embase, CINAHL, PsycINFO, Biological Abstracts on Ovid, and
      The Cochrane Library (January 2009, repeated January 2013) through to February
      2013. RESULTS: Eight RCTs were identified in the systematic search. Six compared
      exercise versus usual care. One study assessed the effect of a cycling programme
      versus muscle strengthening and toning exercises. The final study compared the
      effect of adding specific exercise advice and motivational skills to a simple
      walking programme. The review found that exercise improved levels of exercise
      activity (n = 13, standard mean difference [SMD] 1.81, CI 0.44 to 3.18, p =
      0.01). No beneficial effect was found on negative (n = 84, SMD = -0.54, CI -1.79
      to 0.71, p = 0.40) or positive symptoms of schizophrenia (n = 84, SMD = -1.66, CI
      -3.78 to 0.45, p = 0.12). No change was found on body mass index compared with
      usual care (n = 151, SMD = -0.24, CI -0.56 to 0.08, p = 0.14), or body weight (n
      = 77, SMD = 0.13, CI -0.32 to 0.58, p = 0.57). No beneficial effect was found on
      anxiety and depressive symptoms (n = 94, SMD = -0.26, CI -0.91 to 0.39, p =
      0.43), or quality of life in respect of physical and mental domains. CONCLUSIONS:
      This systematic review showed that exercise therapies can lead to a modest
      increase in levels of exercise activity but overall there was no noticeable
      change for symptoms of mental health, body mass index, and body weight.

PMID- 24751161
TI  - NCAM deficiency in the mouse forebrain impairs innate and learned avoidance
      behaviours.
AB  - The neural cell adhesion molecule (NCAM) has been implicated in the development
      and plasticity of neural circuits and the control of hippocampus- and amygdala
      dependent learning and behaviour. Previous studies in constitutive NCAM null
      mutants identified emotional behaviour deficits related to disturbances of
      hippocampal and amygdala functions. Here, we studied these behaviours in mice
      conditionally deficient in NCAM in the postmigratory forebrain neurons. We report
      deficits in both innate and learned avoidance behaviours, as observed in elevated
      plus maze and passive avoidance tasks. In contrast, general locomotor activity,
      trait anxiety or neophobia were unaffected by the mutation. Altered avoidance
      behaviour of the conditional NCAM mutants was associated with a deficit in
      serotonergic signalling, as indicated by their reduced responsiveness to (+/-)-8
      hydroxy-2-(dipropylamino)-tetralin-induced hypothermia. Another serotonin
      dependent behaviour, namely intermale aggression that is massively increased in
      constitutively NCAM-deficient mice, was not affected in the forebrain-specific
      mutants. Our data suggest that genetically or environmentally induced changes of
      NCAM expression in the late postnatal and mature forebrain determine avoidance
      behaviour and serotonin (5-HT)1A receptor signalling.

PMID- 24751162
TI  - Two-year field analysis of reduced recalcitrance transgenic switchgrass.
AB  - Switchgrass (Panicum virgatum L.) is a leading candidate for a dedicated
      lignocellulosic biofuel feedstock owing to its high biomass production, wide
      adaptation and low agronomic input requirements. Lignin in cell walls of
      switchgrass, and other lignocellulosic feedstocks, severely limits the
      accessibility of cell wall carbohydrates to enzymatic breakdown into fermentable
      sugars and subsequently biofuels. Low-lignin transgenic switchgrass plants
      produced by the down-regulation of caffeic acid O-methyltransferase (COMT), a
      lignin biosynthetic enzyme, were analysed in the field for two growing seasons.
      COMT transcript abundance, lignin content and the syringyl/guaiacyl lignin
      monomer ratio were consistently lower in the COMT-down-regulated plants
      throughout the duration of the field trial. In general, analyses with fully
      established plants harvested during the second growing season produced results
      that were similar to those observed in previous greenhouse studies with these
      plants. Sugar release was improved by up to 34% and ethanol yield by up to 28% in
      the transgenic lines relative to controls. Additionally, these results were
      obtained using senesced plant material harvested at the end of the growing
      season, compared with the young, green tissue that was used in the greenhouse
      experiments. Another important finding was that transgenic plants were not more
      susceptible to rust (Puccinia emaculata). The results of this study suggest that
      lignin down-regulation in switchgrass can confer real-world improvements in
      biofuel yield without negative consequences to biomass yield or disease
      susceptibility. 

PMID- 24751164
TI  - Schmallenberg virus antibodies in adult cows and maternal antibodies in calves.

PMID- 24751163
TI  - Structural determinants of human zeta-globin mRNA stability.
AB  - BACKGROUND: The normal accumulation of adult alpha and beta globins in definitive
      erythrocytes is critically dependent upon processes that ensure that the cognate
      mRNAs are maintained at high levels in transcriptionally silent, but
      translationally active progenitor cells. The impact of these post-transcriptional
      regulatory events on the expression of embryonic zeta globin is not known, as its
      encoding mRNA is not normally transcribed during adult erythropoiesis. Recently,
      though, zeta globin has been recognized as a potential therapeutic for alpha
      thalassemia and sickle-cell disease, raising practical questions about
      constitutive post-transcriptional processes that may enhance, or possibly
      prohibit, the expression of exogenous or derepresssed endogenous zeta-globin
      genes in definitive erythroid progenitors. METHODS: The present study assesses
      mRNA half-life in intact cells using a pulse-chase approach; identifies cis
      acting determinants of zeta-globin mRNA stability using a saturation mutagenesis
      strategy; establishes critical 3'UTR secondary structures using an in vitro
      enzymatic mapping method; and identifies trans-acting effector factors using an
      affinity chromatographical procedure. RESULTS: We specify a tetranucleotide 3'UTR
      motif that is required for the high-level accumulation of zeta-globin transcripts
      in cultured cells, and formally demonstrate that it prolongs their cytoplasmic
      half-lives. Surprisingly, the zeta-globin mRNA stability motif does not function
      autonomously, predicting an activity that is subject to structural constraints
      that we subsequently specify. Additional studies demonstrate that the zeta-globin
      mRNA stability motif is targeted by AUF1, a ubiquitous RNA-binding protein that
      enhances the half-life of adult beta-globin mRNA, suggesting commonalities in
      post-transcriptional processes that regulate globin transcripts at all stages of
      mammalian development. CONCLUSIONS: These data demonstrate a mechanism for zeta
      globin mRNA stability that exists in definitive erythropoiesis and is available
      for therapeutic manipulation in alpha thalassemia and sickle-cell disease.

PMID- 24751165
TI  - Reducing the cesarean rate: our time is now.

PMID- 24751167
TI  - Genomic Resources Notes Accepted 1 February 2014 - 31 March 2014.
AB  - This article documents the public availability of transcriptome sequence data and
      assembled, annotated unigenes for the marmot flea, Oropsylla silantiewi.(1.) 

PMID- 24751166
TI  - Treatment practices, outcomes, and costs of multidrug-resistant and extensively
      drug-resistant tuberculosis, United States, 2005-2007.
AB  - To describe factors associated with multidrug-resistant (MDR), including
      extensively-drug-resistant (XDR), tuberculosis (TB) in the United States, we
      abstracted inpatient, laboratory, and public health clinic records of a sample of
      MDR TB patients reported to the Centers for Disease Control and Prevention from
      California, New York City, and Texas during 2005-2007. At initial diagnosis, MDR
      TB was detected in 94% of 130 MDR TB patients and XDR TB in 80% of 5 XDR TB
      patients. Mutually exclusive resistance was 4% XDR, 17% pre-XDR, 24% total first
      line resistance, 43% isoniazid/rifampin/rifabutin-plus-other resistance, and 13%
      isoniazid/rifampin/rifabutin-only resistance. Nearly three-quarters of patients
      were hospitalized, 78% completed treatment, and 9% died during treatment. Direct
      costs, mostly covered by the public sector, averaged $134,000 per MDR TB and
      $430,000 per XDR TB patient; in comparison, estimated cost per non-MDR TB patient
      is $17,000. Drug resistance was extensive, care was complex, treatment completion
      rates were high, and treatment was expensive. 

PMID- 24751168
TI  - Impact of age on the association between CKD and the risk of future coronary
      events.
AB  - BACKGROUND: Elucidation of the relationship between age, kidney function, and
      absolute coronary risk would facilitate efforts to promote chronic kidney disease
      (CKD) as a high-risk state for future vascular events and justify current
      recommendations for statin treatment in CKD. STUDY DESIGN: Population-based
      study. SETTING & PARTICIPANTS: 1,268,538 people with data for estimated
      glomerular filtration rate and albuminuria who were treated in a single Canadian
      province. PREDICTORS: CKD risk groups (G1, G2, G3a, G3b, and G4 had estimated
      glomerular filtration rate >=90, 60-89.9, 45-59.9, 30-44.9, and 15-29.9
      mL/min/1.73 m2, respectively; A1, A2, and A3 had albuminuria with albumin
      creatinine ratio [ACR]<30 mg/g or dipstick urinalysis negative, ACR of 30-300
      mg/g or dipstick trace or 1+, and ACR >300 mg/g or dipstick >= 2+, respectively)
      and age (<40, 40-49, >=50 years). OUTCOMES: Rates of coronary death or nonfatal
      myocardial infarction (expressed per 1,000 person-years), stratified by age, sex,
      and CKD stage. MEASUREMENTS: The first available serum creatinine value and the
      corresponding date were set as the index serum creatinine value and index date,
      respectively. ACR or dipstick urinalysis data were obtained from the periods
      defined by 6 months before and after the index creatinine value. RESULTS:
      Absolute rates of coronary death or nonfatal myocardial infarction were
      consistently greater than 10 per 1,000 person-years for people with CKD and 50
      years or older, regardless of CKD stage. However, absolute rates of the composite
      outcome were consistently less than 10 per 1,000 person-years for those younger
      than 50 years. LIMITATIONS: Single Canadian province, median follow-up only 4.0
      years. CONCLUSIONS: People with CKD who are 50 years or older should be
      considered at the highest risk of coronary events. In contrast, consideration of
      other risk factors will be required when assessing future risk among people with
      CKD who are younger than 50 years.

PMID- 24751169
TI  - Echocardiography in hemodialysis patients: uses and challenges.
AB  - Patients with end-stage renal disease undergoing hemodialysis have high rates of
      morbidity and mortality. Cardiovascular disease accounts for almost half of this
      mortality, with the single most common cause being sudden cardiac death. Early
      detection of abnormalities in cardiac structure and function may be important to
      allow timely and appropriate cardiac interventions. Echocardiography is
      noninvasive cardiac imaging that is widely available and provides invaluable
      information on cardiac morphology and function. However, it has limitations.
      Echocardiography is operator dependent, and image quality can vary depending on
      the operator's experience and the patient's acoustic window. Hemodialysis
      patients undergo regular hemodynamic changes that also may affect
      echocardiographic findings. An understanding of the prognostic significance and
      interpretation of echocardiographic results in this setting is important for
      patient care. There are some emerging techniques in echocardiographic imaging
      that can provide more detailed and accurate information compared with
      conventional 2-dimensional echocardiography. Use of these novel tools may further
      our understanding of the pathophysiology of cardiac disease in patients with end
      stage renal disease undergoing hemodialysis. 

PMID- 24751170
TI  - Peritoneal dialysis-related peritonitis: towards improving evidence, practices,
      and outcomes.
AB  - Peritonitis is a common serious complication of peritoneal dialysis that results
      in considerable morbidity, mortality, and health care costs. It also
      significantly limits the use of this important dialysis modality. Despite its
      importance as a patient safety issue, peritonitis practices and outcomes vary
      markedly and unacceptably among different centers, regions, and countries. This
      article reviews peritonitis risk factors, diagnosis, treatment, and prevention,
      particularly focusing on potential drivers of variable practices and outcomes,
      controversial or unresolved areas, and promising avenues warranting further
      research. Potential strategies for augmenting the existing limited evidence base
      and reducing the gap between evidence-based best practice and actual practice
      also are discussed. 

PMID- 24751171
TI  - Antioxidant marine algae phlorotannins and radioprotection: a review of
      experimental evidence.
AB  - Radiation has been widely used for cancer therapy in human medicine. However, the
      side effects of radiation are problematic and can limit its application.
      Radiation generates reactive oxygen species, leading to cell death via multiple
      signaling pathways. The blocking of certain signaling cascades using antioxidants
      represents a compensatory therapy of radiation-induced tissue injury. Although
      synthetic chemicals have been investigated in recent decades, anti-oxidants from
      natural resources have been searched for continuously. Among them, phlorotannins
      from marine algae, including Ecklonia cava, have been shown to protect cells from
      radiation-induced injury as well as oxidative stress. In the present review, the
      radioprotective capacity of phlorotannins derived from marine algae and the
      mechanisms involved are discussed. 

PMID- 24751173
TI  - Increasing girls' physical activity during an organised youth sport basketball
      program: a randomised controlled trial protocol.
AB  - BACKGROUND: Participation in organised youth sports (OYS) has been recommended as
      an opportunity to increase young peoples' moderate-to-vigorous physical activity
      (MVPA) levels. Participants, however, spend a considerable proportion of time
      during OYS inactive. The purpose of this study, therefore, was to investigate
      whether coaches who attended coach education sessions (where education on
      increasing MVPA and decreasing inactivity during training was delivered) can
      increase players' MVPA during training sessions over a 5-day basketball program
      compared to coaches who did not receive coach education sessions. METHODS/DESIGN:
      A convenience sample of 80 female players and 8 coaches were recruited into the
      UWS School Holiday Basketball Program in Greater Western Sydney, Australia. A two
      arm, parallel-group randomised controlled trial was employed to investigate
      whether coaches who attended 2 coach education sessions (compared with a no
      treatment control) can increase their players' MVPA during training sessions over
      a 5-day basketball program. Objectively measured physical activity, directly
      observed lesson context and leader behaviour, player motivation, players'
      perceived autonomy support, and coaching information (regarding training session
      planning, estimations on player physical activity and lesson context during
      training, perceived ability to modify training sessions, perceived importance of
      physical activity during training, intention to increase physical activity/reduce
      inactivity, and likelihood of increasing physical activity/reducing inactivity)
      were assessed at baseline (day 1) and at follow-up (day 5). Linear mixed models
      will be used to analyse between arm differences in changes from baseline to
      follow-up on all outcomes. DISCUSSION: The current trial protocol describes, to
      our knowledge, the first trial conducted in an OYS context to investigate the
      efficacy of an intervention, relative to a control, in increasing MVPA. This
      study's findings will provide evidence to inform strategies targeting coaches to
      increase MVPA in OYS, which could have major public health implications, given
      the high proportion of children and adolescents who participate in OYS globally.
      TRIAL REGISTRATION: This trial is registered with the Australian New Zealand
      Clinical Trials Registry, ACTRN12613001099718.

PMID- 24751174
TI  - Exploration of presence/absence variation and corresponding polymorphic markers
      in soybean genome.
AB  - This study was designed to reveal the genome-wide distribution of
      presence/absence variation (PAV) and to establish a database of polymorphic PAV
      markers in soybean. The 33 soybean whole-genome sequences were compared to each
      other with that of Williams 82 as a reference genome. A total of 33,127 PAVs were
      detected and 28,912 PAV markers with their primer sequences were designed as the
      database NJAUSoyPAV_1.0. The PAVs scattered on whole genome while only 518 (1.8%)
      overlapped with simple sequence repeats (SSRs) in BARCSOYSSR_1.0 database. In a
      random sample of 800 PAVs, 713 (89.13%) showed polymorphism among the 12
      differential genotypes. Using 126 PAVs and 108 SSRs to test a Chinese soybean
      germplasm collection composed of 828 Glycine soja Sieb. et Zucc. and Glycine max
      (L.) Merr. accessions, the per locus allele number and its variation appeared
      less in PAVs than in SSRs. The distinctness among alleles/bands of PCR
      (polymerase chain reaction) products showed better in PAVs than in SSRs,
      potential in accurate marker-assisted allele selection. The association mapping
      results showed SSR + PAV was more powerful than any single marker systems. The
      NJAUSoyPAV_1.0 database has enriched the source of PCR markers, and may fit the
      materials with a range of per locus allele numbers, if jointly used with SSR
      markers. 

PMID- 24751172
TI  - Pre-clinical and Clinical Safety Studies of CMX-2043: a cytoprotective lipoic
      acid analogue for ischaemia-reperfusion injury.
AB  - CMX-2043 is an alpha-lipoic acid analogue targeted to reduction of cellular
      injury and organ damage due to ischaemia-reperfusion injury (IRI). It has been
      shown to be effective in a rat model of cardiac IRI. The studies here reported
      evaluate its safety and pharmacokinetic profile in preparation for human clinical
      studies in procedures associated with IRI. Safety and tolerability were tested in
      standard pre-clinical in vitro and animal models and in a Phase 1 human clinical
      trial. CMX-2043 did not bind to a wide range of receptors and specific targets at
      approximately 4 MUg/mL (10 MUM). It was not mutagenic by Ames assay, did not
      produce chromosome aberrations in Chinese hamster ovary (CHO) cells, and was
      negative for clastogenic potential. Toxicological studies in rats including both
      single and 14-day repeat intravenous doses and in dogs (single intravenous dose)
      with a 2-week recovery period were conducted. The NOAEL in rats and dogs was 30
      and >10 mg/kg, respectively. No serious adverse events were reported in a placebo
      controlled, sequential dose escalation Phase 1 clinical trial. The low toxicity
      in the pre-clinical studies and the absence of adverse events in the Phase 1
      trial have supported investigation of CMX-2043 in a human efficacy trial. 

PMID- 24751175
TI  - A call for revising the strengthening the reporting of observational studies in
      epidemiology statement to include ecologic studies.

PMID- 24751176
TI  - Combining agreement and frequency rating scales to optimize psychometrics in
      measuring behavioral health functioning.
AB  - OBJECTIVE: The goal of this article was to investigate optimal functioning of
      using frequency vs. agreement rating scales in two subdomains of the newly
      developed Work Disability Functional Assessment Battery: the Mood & Emotions and
      Behavioral Control scales. STUDY DESIGN AND SETTING: A psychometric study
      comparing rating scale performance embedded in a cross-sectional survey used for
      developing a new instrument to measure behavioral health functioning among adults
      applying for disability benefits in the United States was performed. RESULTS:
      Within the sample of 1,017 respondents, the range of response category
      endorsement was similar for both frequency and agreement item types for both
      scales. There were fewer missing values in the frequency items than the agreement
      items. Both frequency and agreement items showed acceptable reliability. The
      frequency items demonstrated optimal effectiveness around the mean +/- 1-2
      standard deviation score range; the agreement items performed better at the
      extreme score ranges. CONCLUSION: Findings suggest an optimal response format
      requires a mix of both agreement-based and frequency-based items. Frequency items
      perform better in the normal range of responses, capturing specific behaviors,
      reactions, or situations that may elicit a specific response. Agreement items do
      better for those whose scores are more extreme and capture subjective content
      related to general attitudes, behaviors, or feelings of work-related behavioral
      health functioning.

PMID- 24751177
TI  - Poor agreement between family-level and neighborhood-level income measures among
      urban families with children.

PMID- 24751178
TI  - Authors should consider reviewer comments on a rejected article to improve their
      article before submission to the next journal.

PMID- 24751179
TI  - Effective writing and dealing with reviewers.

PMID- 24751180
TI  - Response to Keriel-Gascou et al. Addressing assumptions on the stepped wedge
      randomized trial design.

PMID- 24751182
TI  - Linezolid-Resistant Staphylococcus epidermidis, Portugal, 2012.

PMID- 24751181
TI  - Human papillomavirus prevalence in oropharyngeal cancer before vaccine
      introduction, United States.
AB  - We conducted a study to determine prevalence of HPV types in oropharyngeal
      cancers in the United States and establish a prevaccine baseline for monitoring
      the impact of vaccination. HPV DNA was extracted from tumor tissue samples from
      patients in whom cancer was diagnosed during 1995-2005. The samples were obtained
      from cancer registries and Residual Tissue Repository Program sites in the United
      States. HPV was detected and typed by using PCR reverse line blot assays. Among
      557 invasive oropharyngeal squamous cell carcinomas, 72% were positive for HPV
      and 62% for vaccine types HPV16 or 18. Prevalence of HPV-16/18 was lower in women
      (53%) than in men (66%), and lower in non-Hispanic Black patients (31%) than in
      other racial/ethnic groups (68%-80%). Results indicate that vaccines could
      prevent most oropharyngeal cancers in the United States, but their effect may
      vary by demographic variables. 

PMID- 24751183
TI  - Concordance of Shape Risk Scale, a new pressure ulcer risk tool, with Braden
      Scale.
AB  - The occurrence of pressure ulcers was examined in a cross-sectional study in 23
      health care facilities and in home care involving 548 patients. The screening of
      pressure ulcer risk was assessed simultaneously using the Braden Scale and the
      new Shape Risk Scale (SRS), and the results were compared. The overall prevalence
      of pressure ulcers in the study population was 15.5% (85/548). The Braden Scale
      was performed as described in the literature. The direct concordance of the
      Braden and SRS scales was 46%. In more than 90% of cases, the SRS classified
      patients as well as or better than the Braden Scale. The SRS allocates patients
      significantly different from the Braden Scale into the risk categories,
      especially the difference is significant between the low and medium-risk
      categories. The greatest advantage of SRS to Braden Scale is that it correctly
      identifies patients with low risk of pressure ulcers. It is interesting that the
      two risk scores, taking into consideration the basically different
      pathophysiological factors, can still give rather similar results. The users
      considered that both scales are easy to use. 

PMID- 24751184
TI  - Reperfusion therapy with low-dose insulin or insulin-like growth factor 2;
      myocardial function and infarct size in a porcine model of ischaemia and
      reperfusion.
AB  - In an open-chest porcine model, we examined whether myocardial pharmacological
      conditioning at the time of reperfusion with low-dose insulin or insulin-like
      growth factor 2 (IGF2), not affecting serum glucose levels, could reduce infarct
      size and improve functional recovery. Two groups of anaesthetized pigs with
      either 60 or 40 min. of left anterior descending artery occlusion (total n = 42)
      were randomized to receive either 0.9% saline, insulin or IGF2 infusion for 15
      min., starting 5 min. before a 180-min. reperfusion period. Repeated fluorescent
      microsphere injections were used to confirm ischaemia and reperfusion. Area at
      risk and infarct size was determined with Evans blue and triphenyltetrazolium
      chloride staining. Local myocardial function was evaluated with multi-layer
      radial tissue Doppler strain and speckle-tracking strain from epicardial
      echocardiography. Western blotting and TUNEL staining were performed to explore
      apoptosis. Infarct size did not differ between treatment groups and was 56.7 +/-
      6.8%, 49.7 +/- 9.6%, 56.2 +/- 8.0% of area at risk for control, insulin and IGF2
      group, respectively, in the 60-min. occlusion series. Corresponding values were
      45.6 +/- 6.0%, 48.4 +/- 7.2% and 34.1 +/- 5.8% after 40-min. occlusion. Global
      and local cardiac function did not differ between treatment groups. No
      differences related to treatment could be found in myocardial tissue cleaved
      caspase-3 content or the degree of TUNEL staining. Reperfusion therapy with low
      dose insulin or with IGF2 neither reduced infarct size nor improved function in
      reperfused myocardium in this in vivo porcine model. 

PMID- 24751185
TI  - Response to commentaries regarding the Triadic Systems Model perspective.

PMID- 24751186
TI  - Using genotyping data to assign markers to their chromosome type and to infer the
      sex of individuals: a Bayesian model-based classifier.
AB  - The recent democratization of next-generation-sequencing-based approaches towards
      nonmodel species has made it cost-effective to produce large genotyping data sets
      for a wider range of species. However, when no detailed genome assembly is
      available, poor knowledge about the organization of the markers within the genome
      might hamper the optimal use of this abundant information. At the most basic
      level of genomic organization, the type of chromosome (autosomes, sex
      chromosomes, mitochondria or chloroplast in plants) may remain unknown for most
      markers which might be limiting or even misleading in some applications,
      particularly in population genetics. Conversely, the characterization of sex
      linked markers allows molecular sexing of the individuals. In this study, we
      propose a Bayesian model-based classifier named detsex, to assign markers to
      their chromosome type and/or to perform sexing of individuals based on genotyping
      data. The performance of detsex is further evaluated by a comprehensive
      simulation study and by the analysis of real data sets from various origins
      (microsatellite and SNP data derived from genotyping assay designs and NGS
      experiments). Irrespective of the origin of the markers or the size of the data
      set, detsex was proved efficient (i) to identify the sex-linked markers, (ii) to
      perform molecular sexing of the individuals and (iii) to perform basic quality
      check of the genotyping data sets. The underlying structure of the model also
      allows to consider each of these potential applications either separately or
      jointly. 

PMID- 24751187
TI  - The effects of mid-life socioeconomic disadvantage and perceived social support
      on trajectories of subsequent depressive symptoms among older Taiwanese women.
AB  - BACKGROUND: Scant research has taken a life-course perspective to explore the
      longitudinal impact of socioeconomic disadvantage and perceived social support on
      the psychological well-being of older women. We sought to explore whether
      socioeconomic disadvantage and perceived social support in mid-life are
      associated with subsequent depressive symptomatology among older Taiwanese women.
      METHODS: This study was based on data from the Taiwan Longitudinal Study on Aging
      conducted on a nationally representative sample (n = 1,073) of women aged 50 and
      above with a 12-year follow up. Mid-life socioeconomic disadvantage was assessed
      by socioeconomic status (SES) (i.e., educational attainment, major lifetime
      occupation in adulthood, and employment status) and economic strain. Perceived
      social support included three dimensions: listening, caring, and sick care. We
      used the short form of the Center of Epidemiological Studies-Depression (CES-D)
      scale that measures depressive symptomatology within two domains (negative affect
      and lack of positive affect). Growth curve models were employed to predict the
      relationships between mid-life socioeconomic disadvantage, perceived social
      support, and subsequent depressive trajectories, controlling for aging effects.
      RESULTS: Multivariate analyses demonstrated older women in a socioeconomic
      disadvantaged position are more likely to report higher initial levels of
      depressive symptoms in both domains; lack of formal education did not exacerbate
      depressive symptoms in the lack of positive affect domain over time. In addition,
      mid-life perceived positive social support in caring and sick care was associated
      with lower initial levels of depressive symptoms in both domains. CONCLUSIONS:
      Our results suggest independent effects of mid-life socioeconomic disadvantage
      and perceived social support on subsequent depressive symptomatology among older
      Taiwanese women.

PMID- 24751188
TI  - Editorial comment.

PMID- 24751189
TI  - Richard Francis Jones--opening doors and diversifying the urologic workforce: a
      pioneer in the training of African urologic surgeons in North America.

PMID- 24751190
TI  - Reply: To PMID 24751188.

PMID- 24751191
TI  - Evidence for unapparent Brucella canis infections among adults with occupational
      exposure to dogs.
AB  - Human serological assays designed to detect brucellosis will miss infections
      caused by Brucella canis, and low levels of periodic bacteremia limit diagnosis
      by blood culture. Recent B. canis outbreaks in dogs and concomitant illnesses in
      caretakers suggest that unapparent human infections may be occurring. With more
      than a quarter of a million persons in occupations involving dogs, and nearly 80
      million dog owners in the United States, this pathogen is an under-recognized
      human health threat. To investigate occupational exposure to B. canis, we adapted
      a commercial canine serological assay and present the first controlled
      seroepidemiological study of human B. canis infections in recent years. 306
      adults with occupational exposure to dogs and 101 non-matched, non-canine-exposed
      subjects were enrolled. Antibodies were detected using the canine D-Tec((r)) CB
      rapid slide agglutination test (RSAT) kit with a secondary 2-mercaptoethanol (ME)
      RSAT. Results were validated on a blinded subset of sera with an additional RSAT
      and indirect enzyme-linked immunoassay at the National Administration of
      Laboratories and Health Institutes (ANLIS) in Argentina. Seroprevalence ranged
      from 10.8% (RSAT) to 3.6% (ME-RSAT) among canine-exposed subjects. Kennel
      employees were more likely to test RSAT seropositive compared with other canine
      exposures (OR = 2.7; 95% CI, 1.3-5.8); however, low seroprevalence limited
      meaningful occupational risk factor analyses. Two seropositive participants
      reported experiencing symptoms consistent with brucellosis and having exposure to
      B. canis-infected dogs; however, temporality of symptom onset with reported
      exposure could not be determined. D-Tec((r)) CB results had substantial agreement
      with ANLIS assays (Cohen's kappa = 0.60-0.68). These data add to a growing body
      of literature suggesting that people occupationally exposed to dogs may be at
      risk of unapparent B. canis infection. It seems prudent to consider B. canis as
      an occupational public health concern and encourage the development of
      serological assays to detect human B. canis infections.

PMID- 24751192
TI  - Osteoarthritis, obesity and weight loss: evidence, hypotheses and horizons - a
      scoping review.
AB  - Obesity is widely acknowledged as a risk factor for both the incidence and
      progression of osteoarthritis, and has a negative influence on outcomes. Loss of
      at least 10% of body weight, coupled with exercise, is recognized as a
      cornerstone in the management of obese patients with osteoarthritis, and can lead
      to significant improvement in symptoms, pain relief, physical function and health
      related quality of life. However, questions still remain surrounding optimal
      management. Given the significant health, social and economic burden of
      osteoarthritis, especially in obese patients, it is imperative to advance our
      knowledge of osteoarthritis and obesity, and apply this to improving care and
      outcomes. This paper overviews what is already known about osteoarthritis and
      obesity, discusses current key challenges and ongoing hypotheses arising from
      research in these areas, and finally, postulates what the future may hold in
      terms of new horizons for obese patients with osteoarthritis. 

PMID- 24751193
TI  - Plant-based vaccines: novel and low-cost possible route for Mediterranean
      innovative vaccination strategies.
AB  - A plant bioreactor has enormous capability as a system that supports many
      biological activities, that is, production of plant bodies, virus-like particles
      (VLPs), and vaccines. Foreign gene expression is an efficient mechanism for
      getting protein vaccines against different human viral and nonviral diseases.
      Plants make it easy to deal with safe, inexpensive, and provide trouble-free
      storage. The broad spectrum of safe gene promoters is being used to avoid risk
      assessments. Engineered virus-based vectors have no side effect. The process can
      be manipulated as follows: (a) retrieve and select gene encoding, use an
      antigenic protein from GenBank and/or from a viral-genome sequence, (b) design
      and construct hybrid-virus vectors (viral vector with a gene of interest)
      eventually flanked by plant-specific genetic regulatory elements for constitutive
      expression for obtaining chimeric virus, (c) gene transformation and/or
      transfection, for transient expression, into a plant-host model, that is,
      tobacco, to get protocols processed positively, and then moving into edible host
      plants, (d) confirmation of protein expression by bioassay, PCR-associated tests
      (RT-PCR), Northern and Western blotting analysis, and serological assay (ELISA),
      (e) expression for adjuvant recombinant protein seeking better antigenicity, (f)
      extraction and purification of expressed protein for identification and dosing,
      (g) antigenicity capability evaluated using parental or oral delivery in animal
      models (mice and/or rabbit immunization), and (h) growing of construct-treated
      edible crops in protective green houses. Some successful cases of heterologous
      gene-expressed protein, as edible vaccine, are being discussed, that is,
      hepatitis C virus (HCV). R9 mimotope, also named hypervariable region 1 (HVR1),
      was derived from the HVR1 of HCV. It was used as a potential neutralizing epitope
      of HCV. The mimotope was expressed using cucumber mosaic virus coat protein (CP),
      alfalfa mosaic virus CP P3/RNA3, and tobacco mosaic virus (TMV) CP-tobacco mild
      green mosaic virus (TMGMV) CP as expression vectors into tobacco plants.
      Expressed recombinant protein has not only been confirmed as a therapeutic but
      also as a diagnostic tool. Herpes simplex virus 2 (HSV-2), HSV-2 gD, and HSV-2
      VP16 subunits were transfected into tobacco plants, using TMV CP-TMGMV CP
      expression vectors. 

PMID- 24751194
TI  - The role of environmental, virological and vector interactions in dictating
      biological transmission of arthropod-borne viruses by mosquitoes.
AB  - Arthropod-borne viruses (arboviruses) are transmitted between vertebrate hosts
      and arthropod vectors. An inherently complex interaction among virus, vector, and
      the environment determines successful transmission of the virus. Once believed to
      be "flying syringes," recent advances in the field have demonstrated that
      mosquito genetics, microbiota, salivary components, and mosquito innate immune
      responses all play important roles in modulating arbovirus transmissibility. The
      literature on the interaction among virus, mosquito, and environment has expanded
      dramatically in the preceding decade and the utilization of next-generation
      sequencing and transgenic vector methodologies assuredly will increase the pace
      of knowledge acquisition in this field. This chapter outlines the interplay among
      the three factors in both direct physical and biochemical manners as well as
      indirectly through superinfection barriers and altered induction of innate immune
      responses in mosquito vectors. The culmination of the aforementioned interactions
      and the arms race between the mosquito innate immune response and the capacity of
      arboviruses to antagonize such a response ultimately results in the subjugation
      of mosquito cells for viral replication and subsequent transmission.

PMID- 24751195
TI  - Biology, genome organization, and evolution of parvoviruses in marine shrimp.
AB  - As shrimp aquaculture has evolved from a subsistent farming activity to an
      economically important global industry, viral diseases have also become a serious
      threat to the sustainable growth and productivity of this industry. Parvoviruses
      represent an economically important group of viruses that has greatly affected
      shrimp aquaculture. In the early 1980s, an outbreak of a shrimp parvovirus,
      infectious hypodermal and hematopoietic necrosis virus (IHHNV), led to the
      collapse of penaeid shrimp farming in the Americas. Since then, considerable
      progress has been made in characterizing the parvoviruses of shrimp and
      developing diagnostic methods aimed to preventing the spread of diseases caused
      by these viruses. To date, four parvoviruses are known that infect shrimp; these
      include IHHNV, hepatopancreatic parvovirus (HPV), spawner-isolated mortality
      virus (SMV), and lymphoid organ parvo-like virus. Due to the economic
      repercussions that IHHNV and HPV outbreaks have caused to shrimp farming over the
      years, studies have been focused mostly on these two pathogens, while information
      on SMV and LPV remains limited. IHHNV was the first shrimp virus to be sequenced
      and the first for which highly sensitive diagnostic methods were developed. IHHNV
      resistant lines of shrimp were also developed to mitigate the losses caused by
      this virus. While the losses due to IHHNV have been largely contained in recent
      years, reports of HPV-induced mortalities in larval stages in hatchery and losses
      due to reduced growth have increased. This review presents a comprehensive
      account of the history and current knowledge on the biology, diagnostics methods,
      genomic features, mechanisms of evolution, and management strategies of shrimp
      parvoviruses. We also highlighted areas where research efforts should be focused
      in order to gain further insight on the mechanisms of parvoviral pathogenicity in
      shrimp that will help to prevent future losses caused by these viruses.

PMID- 24751196
TI  - Circulative, "nonpropagative" virus transmission: an orchestra of virus-, insect
      , and plant-derived instruments.
AB  - Species of plant viruses within the Luteoviridae, Geminiviridae, and Nanoviridae
      are transmitted by phloem-feeding insects in a circulative, nonpropagative
      manner. The precise route of virus movement through the vector can differ across
      and within virus families, but these viruses all share many biological,
      biochemical, and ecological features. All share temporal and spatial constraints
      with respect to transmission efficiency. The viruses also induce physiological
      changes in their plant hosts resulting in behavioral changes in the insects that
      optimize the transmission of virus to new hosts. Virus proteins interact with
      insect, endosymbiont, and plant proteins to orchestrate, directly and indirectly,
      virus movement in insects and plants to facilitate transmission. Knowledge of
      these complex interactions allows for the development of new tools to reduce or
      prevent transmission, to quickly identify important vector populations, and to
      improve the management of these economically important viruses affecting
      agricultural and natural plant populations. 

PMID- 24751197
TI  - Arboviruses pathogenic for domestic and wild animals.
AB  - The objective of this chapter is to provide an updated and concise systematic
      review on taxonomy, history, arthropod vectors, vertebrate hosts, animal disease,
      and geographic distribution of all arboviruses known to date to cause disease in
      homeotherm (endotherm) vertebrates, except those affecting exclusively man. Fifty
      arboviruses pathogenic for animals have been documented worldwide, belonging to
      seven families: Togaviridae (mosquito-borne Eastern, Western, and Venezuelan
      equine encephalilitis viruses; Sindbis, Middelburg, Getah, and Semliki Forest
      viruses), Flaviviridae (mosquito-borne yellow fever, Japanese encephalitis,
      Murray Valley encephalitis, West Nile, Usutu, Israel turkey meningoencephalitis,
      Tembusu and Wesselsbron viruses; tick-borne encephalitis, louping ill, Omsk
      hemorrhagic fever, Kyasanur Forest disease, and Tyuleniy viruses), Bunyaviridae
      (tick-borne Nairobi sheep disease, Soldado, and Bhanja viruses; mosquito-borne
      Rift Valley fever, La Crosse, Snowshoe hare, and Cache Valley viruses; biting
      midges-borne Main Drain, Akabane, Aino, Shuni, and Schmallenberg viruses),
      Reoviridae (biting midges-borne African horse sickness, Kasba, bluetongue,
      epizootic hemorrhagic disease of deer, Ibaraki, equine encephalosis, Peruvian
      horse sickness, and Yunnan viruses), Rhabdoviridae (sandfly/mosquito-borne bovine
      ephemeral fever, vesicular stomatitis-Indiana, vesicular stomatitis-New Jersey,
      vesicular stomatitis-Alagoas, and Coccal viruses), Orthomyxoviridae (tick-borne
      Thogoto virus), and Asfarviridae (tick-borne African swine fever virus). They are
      transmitted to animals by five groups of hematophagous arthropods of the
      subphyllum Chelicerata (order Acarina, families Ixodidae and Argasidae-ticks) or
      members of the class Insecta: mosquitoes (family Culicidae); biting midges
      (family Ceratopogonidae); sandflies (subfamily Phlebotominae); and cimicid bugs
      (family Cimicidae). Arboviral diseases in endotherm animals may therefore be
      classified as: tick-borne (louping ill and tick-borne encephalitis, Omsk
      hemorrhagic fever, Kyasanur Forest disease, Tyuleniy fever, Nairobi sheep
      disease, Soldado fever, Bhanja fever, Thogoto fever, African swine fever),
      mosquito-borne (Eastern, Western, and Venezuelan equine encephalomyelitides,
      Highlands J disease, Getah disease, Semliki Forest disease, yellow fever,
      Japanese encephalitis, Murray Valley encephalitis, West Nile encephalitis, Usutu
      disease, Israel turkey meningoencephalitis, Tembusu disease/duck egg-drop
      syndrome, Wesselsbron disease, La Crosse encephalitis, Snowshoe hare
      encephalitis, Cache Valley disease, Main Drain disease, Rift Valley fever,
      Peruvian horse sickness, Yunnan disease), sandfly-borne (vesicular stomatitis
      Indiana, New Jersey, and Alagoas, Cocal disease), midge-borne (Akabane disease,
      Aino disease, Schmallenberg disease, Shuni disease, African horse sickness, Kasba
      disease, bluetongue, epizootic hemorrhagic disease of deer, Ibaraki disease,
      equine encephalosis, bovine ephemeral fever, Kotonkan disease), and cimicid-borne
      (Buggy Creek disease). Animals infected with these arboviruses regularly develop
      a febrile disease accompanied by various nonspecific symptoms; however,
      additional severe syndromes may occur: neurological diseases (meningitis,
      encephalitis, encephalomyelitis); hemorrhagic symptoms; abortions and congenital
      disorders; or vesicular stomatitis. Certain arboviral diseases cause significant
      economic losses in domestic animals-for example, Eastern, Western and Venezuelan
      equine encephalitides, West Nile encephalitis, Nairobi sheep disease, Rift Valley
      fever, Akabane fever, Schmallenberg disease (emerged recently in Europe), African
      horse sickness, bluetongue, vesicular stomatitis, and African swine fever; all of
      these (except for Akabane and Schmallenberg diseases) are notifiable to the World
      Organisation for Animal Health (OIE, 2012). 

PMID- 24751198
TI  - Synergistic effects of resistance training and protein intake: practical aspects.
AB  - Resistance training is a potent stimulus to increase skeletal muscle mass. The
      muscle protein accretion process depends on a robust synergistic action between
      protein intake and overload. The intake of protein after resistance training
      increases plasma amino acids, which results in the activation of signaling
      molecules leading to increased muscle protein synthesis (MPS) and muscle
      hypertrophy. Although both essential and non-essential amino acids are necessary
      for hypertrophy, the intake of free L-leucine or high-leucine whole proteins has
      been specifically shown to increase the initiation of translation that is
      essential for elevated MPS. The literature supports the use of protein intake
      following resistance-training sessions to enhance MPS; however, less understood
      are the effects of different protein sources and timing protocols on MPS. The sum
      of the adaptions from each individual training session is essential to muscle
      hypertrophy, and thus highlights the importance of an optimal supplementation
      protocol. The aim of this review is to present recent findings reported in the
      literature and to discuss the practical application of these results. In that
      light, new speculations and questions will arise that may direct future
      investigations. The information and recommendations generated in this review
      should be of benefit to clinical dietitians as well as those engaged in sports. 

PMID- 24751199
TI  - Evaluating the systemic right ventricle by cardiovascular magnetic resonance:
      short axis or axial slices?
AB  - OBJECTIVE: To evaluate differences in functional parameters and reproducibility
      between short axis and axial slice orientation in the quantitative evaluation of
      the systemic right ventricle by cardiovascular magnetic resonance. DESIGN: Cross
      sectional evaluation comparing two methods (Bland-Altman). SETTING: Tertiary care
      outpatients. INTERVENTIONS: Quantitative cardiovascular magnetic resonance
      evaluation using short axis or axial slice orientation. MAIN OUTCOME MEASURES:
      Intraobserver variance, interobserver variance and systematic differences in
      systemic right ventricular volumes, ejection fraction, and mass between both
      methods. PATIENTS: Twenty-two patients (mean age 33 +/- 7 years) with systemic
      right ventricle (three with congenitally corrected transposition of the great
      arteries and 19 with atrially switched transposition of the great arteries).
      RESULTS: Compared with short axis slices, analysis of axial slices resulted in
      higher end systolic volume (6.6%, P < .01), while mass (-10.8%, P < .01) and
      ejection fraction (-8.9%, P < .01) turned out lower. Intraobserver and
      interobserver reproducibility were similar for both methods when measuring end
      diastolic and end-systolic volumes. However, ejection fraction and stroke volume
      were measured more consistently in axial orientation, while ventricular mass was
      measured more consistently in short axis orientation. CONCLUSION: There are
      significant differences in volume, mass, and function between measurements in
      axial and short axis orientation. Ejection fraction and stroke volume, which have
      a high clinical relevance, were measured more consistently in axial slice
      orientation. Consequently, we recommend using axial slice orientation in patients
      with a systemic right ventricle.

PMID- 24751200
TI  - Teachers' perceptions of the role of nurses: caring for children who are
      technology-dependent in mainstream schools.
AB  - AIM: This study explored special education teachers' perceptions of the role of
      nurses who specialize in providing nursing care to children who are technology
      dependent in mainstream schools. METHODS: Semistructured interviews with 11
      teachers were conducted, and data were analyzed using inductive content analysis.
      RESULTS: The teachers surveyed thought that the most important role of nurses was
      to maintain good health and safety, as well as to support children's education as
      members of the educational team. Teachers desired that nurses give advice based
      on their professional knowledge to maintain the children's good health and
      safety. In supporting education, nurses were required to support the children's
      autonomy and education, and to act as members of the educational team.
      CONCLUSION: Study findings suggest that, for an optimal relationship with
      teachers, nurses who provide nursing care for children who are technology
      dependent in mainstream schools need not only fulfill medical functions, but also
      support the education of children as members of the educational team.

PMID- 24751201
TI  - The hallux valgus angle of the margo medialis pedis as an alternative to the
      measurement of the metatarsophalangeal hallux valgus angle.
AB  - BACKGROUND: Currently, the metatarsophalangeal angle (hallux valgus angle) is
      measured based on radiographic images. However, using X-ray examinations for
      epidemiological or screening purposes would be unethical, especially in children.
      For this reason it is discussed to measure the hallux valgus angle of the margo
      medialis pedis (medial border of the foot) documented on foot outline drawings or
      foot scans. As a first step on the way to prove the validity of those approaches
      this study assesses the hallux valgus angle measured on the margo medialis pedis
      based on the same x-ray pictures as the metatarsophalangeal hallux valgus.
      METHODS: Radiographic images of the foot were obtained from patients with
      symptomatic hallux valgus malformation. Twelve sets of contact copies of the 63
      originals were made, and were marked and measured according to three different
      methods, each one performed by two observers and with two repeated measurements.
      Thus, data sets from 756 individual assessments were entered into the
      multifactorial statistical analysis.Comparisons were made between the angle of
      the margo medialis pedis and the metatarsophalangeal angle, which was determined
      by two different methods. To determine the inter- and intraobserver reliability
      of the different methods, each assessment was conducted by two independent
      experts and repeated after a period of several weeks. RESULTS: The correlations
      between the hallux valgus angles determined by the three different methods were
      all above r=0.89 (p<0.001) and thus highly significant. The values obtained by
      measuring the margo medialis pedis angle, however, were on average 4.8 degrees
      smaller than the metatarsophalangeal angles. No significant differences were
      found between the observers. No systematic deviations for any observer between
      repeated measurements were detected. CONCLUSIONS: Measurements of the
      radiographic hallux angle of the margo medialis pedis are reliable and show high
      correlation with the metatarsophalangeal angle. Because the hallux valgus angles
      based on margo medialis pedis measurements were slightly but statistically
      significantly smaller, these measurements should be considered conservative
      estimates of the metatarsophalangeal angle. Significant differences between
      hallux valgus angles based on radiographic and non-radiographic material are
      unlikely. However this question has to be treated in a second stage in detail.

PMID- 24751202
TI  - Factors associated with antimicrobial drug use in medicaid programs.
AB  - Using US Medicaid data, we found that 52% of adult Medicaid patients with acute
      respiratory tract infections filled prescriptions for antimicrobial drugs in
      2007. Factors associated with lower likelihood of use were higher county-level
      availability of primary care physicians and state-level participation in a
      campaign for appropriate antimicrobial drug use. 

PMID- 24751203
TI  - Environmental metabarcodes for insects: in silico PCR reveals potential for
      taxonomic bias.
AB  - Studies of insect assemblages are suited to the simultaneous DNA-based
      identification of multiple taxa known as metabarcoding. To obtain accurate
      estimates of diversity, metabarcoding markers ideally possess appropriate
      taxonomic coverage to avoid PCR-amplification bias, as well as sufficient
      sequence divergence to resolve species. We used in silico PCR to compare the
      taxonomic coverage and resolution of newly designed insect metabarcodes
      (targeting 16S) with that of existing markers [16S and cytochrome oxidase c
      subunit I (COI)] and then compared their efficiency in vitro. Existing
      metabarcoding primers amplified in silico <75% of insect species with complete
      mitochondrial genomes available, whereas new primers targeting 16S provided >90%
      coverage. Furthermore, metabarcodes targeting COI appeared to introduce taxonomic
      PCR-amplification bias, typically amplifying a greater percentage of Lepidoptera
      and Diptera species, while failing to amplify certain orders in silico. To test
      whether bias predicted in silico was observed in vitro, we created an artificial
      DNA blend containing equal amounts of DNA from 14 species, representing 11 insect
      orders and one arachnid. We PCR-amplified the blend using five primer sets,
      targeting either COI or 16S, with high-throughput amplicon sequencing yielding
      more than 6 million reads. In vitro results typically corresponded to in silico
      PCR predictions, with newly designed 16S primers detecting 11 insect taxa
      present, thus providing equivalent or better taxonomic coverage than COI
      metabarcodes. Our results demonstrate that in silico PCR is a useful tool for
      predicting taxonomic bias in mixed template PCR and that researchers should be
      wary of potential bias when selecting metabarcoding markers.

PMID- 24751204
TI  - The use of direct-fed microbials to reduce shedding of Escherichia coli O157 in
      beef cattle: a systematic review and meta-analysis.
AB  - Human illness due to infections with Escherichia coli O157 is a serious health
      concern. Infection occurs through direct contact with infected animals or their
      faeces, through contaminated food or water and/or through person-to-person
      transmission. A reduction in faecal E. coli O157 shedding in cattle might reduce
      the burden of human infections. We used systematic review and meta-analysis to
      assess the efficacy of direct-fed microbials (DFM), compared with placebo or no
      treatment, fed during the pre-harvest stage of production in reducing faecal E.
      coli O157 shedding in beef cattle during field trials. Four electronic databases,
      Nebraska Beef Reports and review article reference lists were searched. A total
      of 16 publications assessing faecal shedding at the end of the trial and/or
      throughout the trial period were included. The majority of publicly disseminated
      trials evaluated the prevalence of E. coli O157 faecal shedding; only two
      evaluated the concentration of organisms in faeces. The prevalence of faecal E.
      coli O157 shedding in cattle is significantly reduced by DFM treatments (summary
      effect size for all DFM - OR = 0.46; CI = 0.36-0.60). The DFM combination
      Lactobacillus acidophilus (NP51) and Propionibacterium freudenreichii (NP24) was
      more efficacious in reducing the prevalence of faecal E. coli O157 shedding at
      the time of harvest and throughout the trial period compared with the group of
      other DFM, although this difference was not statistically significant.
      Furthermore, we found that the combination [NP51 and NP24] treatment was more
      efficacious in reducing the prevalence of faecal E. coli O157 shedding at the
      time of harvest and throughout the trial period when fed at the dose of 10(9)
      CFU/animal/day than any lesser amount, although this difference was not
      statistically significant. Feeding beef cattle DFM during the pre-harvest stage
      of production reduces the prevalence of E. coli O157 faecal shedding and might
      effectively reduce human infections.

PMID- 24751205
TI  - Environmental heterogeneity as a universal driver of species richness across
      taxa, biomes and spatial scales.
AB  - Environmental heterogeneity is regarded as one of the most important factors
      governing species richness gradients. An increase in available niche space,
      provision of refuges and opportunities for isolation and divergent adaptation are
      thought to enhance species coexistence, persistence and diversification. However,
      the extent and generality of positive heterogeneity-richness relationships are
      still debated. Apart from widespread evidence supporting positive relationships,
      negative and hump-shaped relationships have also been reported. In a meta
      analysis of 1148 data points from 192 studies worldwide, we examine the strength
      and direction of the relationship between spatial environmental heterogeneity and
      species richness of terrestrial plants and animals. We find that separate effects
      of heterogeneity in land cover, vegetation, climate, soil and topography are
      significantly positive, with vegetation and topographic heterogeneity showing
      particularly strong associations with species richness. The use of equal-area
      study units, spatial grain and spatial extent emerge as key factors influencing
      the strength of heterogeneity-richness relationships, highlighting the pervasive
      influence of spatial scale in heterogeneity-richness studies. We provide the
      first quantitative support for the generality of positive heterogeneity-richness
      relationships across heterogeneity components, habitat types, taxa and spatial
      scales from landscape to global extents, and identify specific needs for future
      comparative heterogeneity-richness research.

PMID- 24751207
TI  - Composite SCCmec element in single-locus variant (ST217) of epidemic MRSA-15
      clone.

PMID- 24751206
TI  - Impact of introducing practical obstetric multi-professional training (PROMPT)
      into maternity units in Victoria, Australia.
AB  - OBJECTIVE: To assess the introduction of Practical Obstetric Multi-professional
      Training (PROMPT) into maternity units and evaluate effects on organisational
      culture and perinatal outcomes. DESIGN: A retrospective cohort study. SETTING:
      Maternity units in eight public hospitals in metropolitan and regional Victoria,
      Australia. POPULATION: Staff in eight maternity units and a total of 43,408
      babies born between July 2008 and December 2011. METHODS: Representatives from
      eight Victorian hospitals underwent a single day of training (Train the Trainer),
      to conduct PROMPT. Organisational culture was compared before and after PROMPT.
      Clinical outcomes were evaluated before, during and after PROMPT. MAIN OUTCOME
      MEASURES: The number of courses run and the proportion of staff trained were
      determined. Organisational culture was measured using the Safety Attitude
      Questionnaire. Clinical measures included Apgar scores at 1 and 5 minutes (Apgar
      1 and Apgar 5), cord lactate, blood loss and length of baby's stay in hospital.
      RESULTS: Seven of the eight hospitals conducted PROMPT. Overall about 50% of
      staff were trained in each year of the study. Significant increases were found in
      Safety Attitude Questionnaire scores representing domains of teamwork (Hedges' g
      0.27, 95% confidence interval [95% CI] 0.13-0.41), safety (Hedges' g 0.28, 95% CI
      0.15-0.42) and perception of management (Hedges' g 0.17, 95% CI 0.04-0.31). There
      were significant improvements in Apgar 1 (OR 0.84, 95% CI 0.77-0.91), cord
      lactates (odds ratio 0.92, 95% CI 0.85-0.99) and average length of baby's stay in
      hospital (Hedges' g 0.03, 95% CI 0.01-0.05) during or after training, but no
      change in Apgar 5 scores or proportion of cases with high blood loss. CONCLUSION:
      PROMPT can be introduced using the Train the Trainer model. Improvements in
      organisational culture and some clinical measures were observed following PROMPT.

PMID- 24751208
TI  - Cost effectiveness.

PMID- 24751209
TI  - Review of foot tumors seen in a university tumor institute.
AB  - Most tumors of the foot and ankle will be benign, and it has been easy for
      clinicians to underestimate the malignant potential of a given tumor. The purpose
      of our study was to gain insight into the incidence of different tumor types
      diagnosed in patients with tumors of the foot and/or ankle treated at the Rizzoli
      Institute from September 1990 to December 2007. Our series included 1170 patients
      and 1170 lesions, with an overall mean age at diagnosis of 43 (range 5 to 81)
      years. Overall, 870 lesions (74.36%) were nonmalignant and 300 (25.65%) were
      malignant. Soft tissue lesions were diagnosed in 189 patients (16.15%), of which
      91 (48.15%) were nonmalignant (pseudotumors or benign). Bone lesions were
      diagnosed in 981 patients (83.85%), of which 779 (79.41%) were nonmalignant.
      Epidemiologic knowledge of foot abnormalities and clinical suspicion, an
      organized diagnostic method, and evidence-based treatment of musculoskeletal
      tumors are essential elements to obtaining optimal results in the treatment of
      malignant foot tumors. 

PMID- 24751210
TI  - The incidence of nonunion after Lapidus arthrodesis using staple fixation.
AB  - Today's foot and ankle surgeon has multiple options when choosing a fixation
      device for Lapidus arthrodesis, many of which have well-documented nonunion
      rates. The present study aimed to fill a void in the current foot and ankle
      literature by establishing a nonunion rate for staple fixation for the Lapidus
      procedure. The present retrospective analysis of the medical record focused on
      nickel-titanium staples that were inserted in a delta configuration to yield a
      stable construct for first metatarsal-cuneiform fusion. The patients were kept
      strictly non-weightbearing for the first 6 weeks postoperatively. Weightbearing
      progressed at that point according to the radiographic findings of each case. The
      data from 35 consecutive patients were analyzed (25 females, 10 males; mean age
      43.1 [range 15 to 72] years in whom a Lapidus arthrodesis was performed using
      staple fixation in 36 feet. The patients were followed until fusion was noted and
      pain had resolved. Pain resolution occurred at 6 weeks in the earliest cases and
      several years in others. The incidence of nonunion was 3 (8.3%) of 36 when staple
      fixation was used for first metatarsal-medial cuneiform arthrodesis. 

PMID- 24751211
TI  - 14-3-3eta is a novel mediator associated with the pathogenesis of rheumatoid
      arthritis and joint damage.
AB  - INTRODUCTION: The aim of this study was to investigate whether 14-3-3eta, a
      specific isoform of a family of proteins regulating processes such as cellular
      signalling, activates cell-signalling pathways and induces factors known to
      contribute to the pathophysiology of rheumatoid arthritis (RA). We also
      investigated whether 14-3-3eta is associated with more severe disease in both
      early and established RA. METHODS: We investigated the effect of 14-3-3eta on the
      activation of RA-relevant signalling cascades and induction of proinflammatory
      mediators that contribute to the joint damage process. 14-3-3eta titres from 33
      patients with early RA (mean RA duration = 1.8 months) and from 40 patients with
      established RA were measured in serum drawn at the 3-year time point of the
      Behandel Strategieen study. The relationship between 14-3-3eta titres and
      standard clinical variables was investigated by correlation analysis. The
      association with radiographic damage and radiographic progression over at least a
      2-year period was investigated using univariate and multivariate regression
      analyses. RESULTS: 14-3-3eta activated selected members of the mitogen-activated
      protein kinase (MAPK) family, mainly extracellular regulated kinase 1/2 and c-Jun
      kinase, but not p38MAPK. Activation by 14-3-3eta, using levels spanning the
      concentration range found in RA patient serum, resulted in the induction of
      inflammatory transcripts such as interleukin 1 (IL-1) and IL-6 and factors linked
      to the joint damage process, such as receptor activator of nuclear factor kappaB
      ligand and matrix metalloproteinase 1. Serum 14-3-3eta correlated significantly
      with rheumatoid factor (RF) (r = 0.43) and anticitrullinated protein antibodies
      (ACPAs) (r = 0.31) in the early RA cohort, but not with C-reactive protein (CRP)
      or the Disease Activity Score in 28 joints in either cohort. Serum 14-3-3eta
      concentrations were significantly higher in patients with radiographically
      assessed joint damage and in those who had radiographic progression. By
      multivariate analysis, we show that 14-3-3eta complemented markers such as CRP,
      RF and ACPA in informing RA radiographic status and/or progression. CONCLUSIONS:
      Extracellular 14-3-3eta activates key signalling cascades and induces factors
      associated with the pathogenesis of RA at concentrations found in patients with
      RA, and its expression is higher in patients with radiographic damage and RA
      progression.

PMID- 24751212
TI  - Skin cancer knowledge and sun protection behavior among nursing students.
AB  - AIM: The objective of this study was to determine skin cancer knowledge and sun
      protection behavior among nursing students. METHODS: A total of 1178 nursing
      students in the Aegean Region of Turkey took part in this descriptive study. A
      score for knowledge on protection against skin cancer and a score for protective
      behavior against skin cancer were calculated. RESULTS: In this study, first year
      students sunbathed more in the middle of the day than fourth year students, and
      their knowledge of skin cancer was lower. No statistical difference was
      determined for protective behavior between the two groups. The knowledge levels
      and protective behavior of first year students were alarmingly low, but the
      average scores for knowledge and behavior of the fourth year university students
      were higher. The knowledge levels of the fourth year students were average but
      their protective behavior was insufficient. It was found that the knowledge
      levels and the levels of protective behavior of light-skinned students were
      higher. CONCLUSION: This study revealed that the knowledge levels and protective
      behavior of first year nursing students against the harmful effects of the sun
      and for protection against skin cancer were alarmingly low. It also showed that
      the knowledge levels of the fourth year nursing students were average, but that
      their protective behavior was very insufficient. These findings suggest that it
      is of extreme importance to acquire knowledge and behavior for protection against
      skin cancers in the education of nursing students.

PMID- 24751213
TI  - Design of an impact evaluation using a mixed methods model--an explanatory
      assessment of the effects of results-based financing mechanisms on maternal
      healthcare services in Malawi.
AB  - BACKGROUND: In this article we present a study design to evaluate the causal
      impact of providing supply-side performance-based financing incentives in
      combination with a demand-side cash transfer component on equitable access to and
      quality of maternal and neonatal healthcare services. This intervention is
      introduced to selected emergency obstetric care facilities and catchment area
      populations in four districts in Malawi. We here describe and discuss our study
      protocol with regard to the research aims, the local implementation context, and
      our rationale for selecting a mixed methods explanatory design with a quasi
      experimental quantitative component. DESIGN: The quantitative research component
      consists of a controlled pre- and post-test design with multiple post-test
      measurements. This allows us to quantitatively measure 'equitable access to
      healthcare services' at the community level and 'healthcare quality' at the
      health facility level. Guided by a theoretical framework of causal relationships,
      we determined a number of input, process, and output indicators to evaluate both
      intended and unintended effects of the intervention. Overall causal impact
      estimates will result from a difference-in-difference analysis comparing selected
      indicators across intervention and control facilities/catchment populations over
      time.To further explain heterogeneity of quantitatively observed effects and to
      understand the experiential dimensions of financial incentives on clients and
      providers, we designed a qualitative component in line with the overall
      explanatory mixed methods approach. This component consists of in-depth
      interviews and focus group discussions with providers, service user, non-users,
      and policy stakeholders. In this explanatory design comprehensive understanding
      of expected and unexpected effects of the intervention on both access and quality
      will emerge through careful triangulation at two levels: across multiple
      quantitative elements and across quantitative and qualitative elements.
      DISCUSSION: Combining a traditional quasi-experimental controlled pre- and post
      test design with an explanatory mixed methods model permits an additional
      assessment of organizational and behavioral changes affecting complex processes.
      Through this impact evaluation approach, our design will not only create robust
      evidence measures for the outcome of interest, but also generate insights on how
      and why the investigated interventions produce certain intended and unintended
      effects and allows for a more in-depth evaluation approach.

PMID- 24751214
TI  - Beyond approval: what is the most appropriate way to use the expanding
      Armamentarium in metastatic castration-resistant prostate cancer and how do we
      move forward?

PMID- 24751215
TI  - Chronic wasting disease agents in nonhuman primates.
AB  - Chronic wasting disease is a prion disease of cervids. Assessment of its zoonotic
      potential is critical. To evaluate primate susceptibility, we tested monkeys from
      2 genera. We found that 100% of intracerebrally inoculated and 92% of orally
      inoculated squirrel monkeys were susceptible, but cynomolgus macaques were not,
      suggesting possible low risk for humans. 

PMID- 24751217
TI  - Noninvasive individual and species identification of jaguars (Panthera onca),
      pumas (Puma concolor) and ocelots (Leopardus pardalis) in Belize, Central America
      using cross-species microsatellites and faecal DNA.
AB  - There is a great need to develop efficient, noninvasive genetic sampling methods
      to study wild populations of multiple, co-occurring, threatened felids. This is
      especially important for molecular scatology studies occurring in challenging
      tropical environments where DNA degrades quickly and the quality of faecal
      samples varies greatly. We optimized 14 polymorphic microsatellite loci for
      jaguars (Panthera onca), pumas (Puma concolor) and ocelots (Leopardus pardalis)
      and assessed their utility for cross-species amplification. Additionally, we
      tested their reliability for species and individual identification using DNA from
      faeces of wild felids detected by a scat detector dog across Belize in Central
      America. All microsatellite loci were successfully amplified in the three target
      species, were polymorphic with average expected heterozygosities of HE = 0.60 +/-
      0.18 (SD) for jaguars, HE = 0.65 +/- 0.21 (SD) for pumas and HE = 0.70 +/- 0.13
      (SD) for ocelots and had an overall PCR amplification success of 61%. We used
      this nuclear DNA primer set to successfully identify species and individuals from
      49% of 1053 field-collected scat samples. This set of optimized microsatellite
      multiplexes represents a powerful tool for future efforts to conduct noninvasive
      studies on multiple, wild Neotropical felids.

PMID- 24751216
TI  - Effects of serotonin-2A receptor binding and gender on personality traits and
      suicidal behavior in borderline personality disorder.
AB  - Impulsivity and aggressiveness are personality traits associated with a
      vulnerability to suicidal behavior. Behavioral expression of these traits differs
      by gender and has been related to central serotonergic function. We assessed the
      relationships between serotonin-2A receptor function, gender, and personality
      traits in borderline personality disorder (BPD), a disorder characterized by
      impulsive-aggression and recurrent suicidal behavior. Participants, who included
      33 BPD patients and 27 healthy controls (HC), were assessed for Axis I and II
      disorders with the Structured Clinical Interview for DSM-IV and the International
      Personality Disorders Examination, and with the Diagnostic Interview for
      Borderline Patients-Revised for BPD. Depressed mood, impulsivity, aggression, and
      temperament were assessed with standardized measures. Positron emission
      tomography with [(18)F]altanserin as ligand and arterial blood sampling was used
      to determine the binding potentials (BPND) of serotonin-2A receptors in 11
      regions of interest. Data were analyzed using Logan graphical analysis,
      controlling for age and non-specific binding. Among BPD subjects, aggression,
      Cluster B co-morbidity, antisocial PD, and childhood abuse were each related to
      altanserin binding. BPND values predicted impulsivity and aggression in BPD
      females (but not BPD males), and in HC males (but not HC females.) Altanserin
      binding was greater in BPD females than males in every contrast, but it did not
      discriminate suicide attempters from non-attempters. Region-specific differences
      in serotonin-2A receptor binding related to diagnosis and gender predicted
      clinical expression of aggression and impulsivity. Vulnerability to suicidal
      behavior in BPD may be related to serotonin-2A binding through expression of
      personality risk factors. 

PMID- 24751218
TI  - Allosteric regulation of phosphofructokinase controls the emergence of glycolytic
      oscillations in isolated yeast cells.
AB  - Oscillations are widely distributed in nature and synchronization of oscillators
      has been described at the cellular level (e.g. heart cells) and at the population
      level (e.g. fireflies). Yeast glycolysis is the best known oscillatory system,
      although it has been studied almost exclusively at the population level (i.e.
      limited to observations of average behaviour in synchronized cultures). We
      studied individual yeast cells that were positioned with optical tweezers in a
      microfluidic chamber to determine the precise conditions for autonomous
      glycolytic oscillations. Hopf bifurcation points were determined experimentally
      in individual cells as a function of glucose and cyanide concentrations. The
      experiments were analyzed in a detailed mathematical model and could be
      interpreted in terms of an oscillatory manifold in a three-dimensional state
      space; crossing the boundaries of the manifold coincides with the onset of
      oscillations and positioning along the longitudinal axis of the volume sets the
      period. The oscillatory manifold could be approximated by allosteric control
      values of phosphofructokinase for ATP and AMP. DATABASE: The mathematical models
      described here have been submitted to the JWS Online Cellular Systems Modelling
      Database and can be accessed at
      http://jjj.mib.ac.uk/webMathematica/UItester.jsp?modelName=gustavsson5. [Database
      section added 14 May 2014 after original online publication].

PMID- 24751219
TI  - One or two things I know about apraxia.

PMID- 24751220
TI  - Best practices for planning events encouraging human-animal interactions.
AB  - Educational events encouraging human-animal interaction include the risk of
      zoonotic disease transmission. It is estimated that 14% of all disease in the USA
      caused by Campylobacter spp., Cryptosporidium spp., Shiga toxin-producing
      Escherichia coli (STEC) O157, non-O157 STECs, Listeria monocytogenes, non
      typhoidal Salmonella enterica and Yersinia enterocolitica were attributable to
      animal contact. This article reviews best practices for organizing events where
      human-animal interactions are encouraged, with the objective of lowering the risk
      of zoonotic disease transmission.

PMID- 24751221
TI  - A facegram for spatial-temporal analysis of facial excursion: applicability in
      the microsurgical reanimation of long-standing paralysis and pretransplantation.
AB  - BACKGROUND: There are several techniques available for facial reanimation, but
      clinicians do not have a simple tool to provide an objective and quantitative
      spatial-temporal analysis of facial movement in order to compare medical,
      surgical and physical therapy. METHODS: We developed specialized software capable
      of simultaneously tracking the position over time of a number of anatomical
      points. This method was tested in 5 different clinical situations: one normal
      subject, and 4 patients with facial disfigurement. RESULTS: A large amount of
      quantitative information can be extracted directly, such as symmetry assessment
      in the contraction and relaxation trajectories. The fact that this plot is on
      scale allows also direct measurements such as maximal extensions. Even smiles
      that at the macro-scale are essentially symmetrical show at the micro-scale small
      asymmetries/variability. CONCLUSION: In this paper, we describe a novel
      quantitative, reliable method, which accurately assesses the fundamental aspects
      of the facial excursion, incorporating spatial and temporal components.

PMID- 24751222
TI  - Comparison between the ICRU rectal point and modern volumetric parameters in
      brachytherapy for locally advanced cervical cancer.
AB  - PURPOSE: The implementation of image-guided brachytherapy in cervical cancer
      raises the problem of adapting the experience acquired with 2D brachytherapy to
      this technique. The GEC-ESTRO (Groupe europeen de curietherapie - European
      Society for Radiotherapy and Oncology) has recommended reporting the dose
      delivered to the rectum in the maximally exposed 2 cm(3) volume, but so far, the
      recommended dose constraints still rely on 2D data. The aim of this study was to
      evaluate the relationship between the doses evaluated at the ICRU rectal point
      and modern dosimetric parameters. MATERIAL AND METHODS: For each patient,
      dosimetric parameters were generated prospectively at the time of dosimetry and
      were reported. For analysis, they were converted in 2 Gy equivalent doses using
      an alpha/beta ratio of 3 with a half-time of repair of 1.5 hours. RESULTS: The
      dosimetric data from 229 consecutive patients treated for locally advanced
      cervical cancer was analyzed. The mean dose calculated at ICRU point (DICRU) was
      55.75 Gy +/- 4.15, while it was 59.27 Gy +/- 6.16 in the maximally exposed 2
      cm(3) of the rectum (P=0.0003). The D2 cm(3) was higher than the DICRU in 78% of
      the cases. The mean difference between D2 cm(3) and DICRU was 3.53 Gy +/- 4.91.
      This difference represented 5.41% +/- 7.40 of the total dose delivered to the
      rectum (EBRT and BT), and 15.49% +/- 24.30 of the dose delivered when considering
      brachytherapy alone. The two parameters were significantly correlated
      (P=0.000001), and related by the equation: D2 cm(3)=0.902 * DICRU + 0.984. The
      r(2) coefficient was 0.369. CONCLUSION: In this large cohort of patients, the
      DICRU significantly underestimates the D2 cm(3). This difference probably results
      from the optimization process itself, which consists in increasing dwell times
      above the ICRU point in the cervix. Considering these findings, caution must be
      taken while implementing image-guided brachytherapy and dose escalation.

PMID- 24751223
TI  - Towards a mechanistic understanding of temperature and enrichment effects on
      species interaction strength, omnivory and food-web structure.
AB  - Revealing the links between species functional traits, interaction strength and
      food-web structure is of paramount importance for understanding and predicting
      the relationships between food-web diversity and stability in a rapidly changing
      world. However, little is known about the interactive effects of environmental
      perturbations on individual species, trophic interactions and ecosystem
      functioning. Here, we combined modelling and laboratory experiments to
      investigate the effects of warming and enrichment on a terrestrial tritrophic
      system. We found that the food-web structure is highly variable and switches
      between exploitative competition and omnivory depending on the effects of
      temperature and enrichment on foraging behaviour and species interaction
      strength. Our model contributes to identifying the mechanisms that explain how
      environmental effects cascade through the food web and influence its topology. We
      conclude that considering environmental factors and flexible food-web structure
      is crucial to improve our ability to predict the impacts of global changes on
      ecosystem diversity and stability.

PMID- 24751224
TI  - Thirty years of practitioner-based projects.

PMID- 24751225
TI  - Research trends in teens' health information behaviour: a review of the
      literature.
AB  - OBJECTIVE: This study aims to examine trends in studies of teens' health
      information behaviour. METHODS: Eighty-two articles published between 2000 and
      2012 were selected and analysed in various aspects: health topics by year,
      information sources, data collection methods, use of theories and models,
      collaborative and interdisciplinary efforts and published journals. RESULTS:
      Fifty-seven per cent of the studies focused on specific health topics, such as
      sexual health, while the rest covered general health topics. Almost half of the
      studies examined how teens search for and use health information on the Internet.
      Surveys were the most popular data collection technique. Only 12.2% were based on
      a theory or model. About 42% were conducted collaboratively by authors from
      multiple disciplines. DISCUSSION AND CONCLUSIONS: With the increasing attention
      to specific health topics and online resources, the health information behaviour
      of teens has been examined more frequently since the mid-2000s. Its
      interdisciplinary nature was evidently shown from various disciplines that the
      authors were affiliated with and the journals of the published studies
      represented. This study suggests that there should be efforts to reflect new
      technology tools, apply mixed methods and increase the engagement level of
      collaboration to evolve this research domain.

PMID- 24751226
TI  - Leisure reading collections in academic health sciences and science libraries:
      results of visits to seven libraries.
AB  - OBJECTIVE: To visit leisure reading collections in academic science and health
      sciences libraries to determine how they function and what role they play in
      their libraries. METHODS: The author visited seven libraries with leisure reading
      collections and carried out a semistructured interview with those responsible
      either for selection of materials or for the establishment of the collection.
      RESULTS: These collections contained a variety of materials, with some libraries
      focusing on health-science-related materials and others on providing recreational
      reading. The size of the collections also varied, from 186 to 9700 books, with
      corresponding differences in budget size. All collections were housed apart, with
      the same loan period as the regular collection. No collections contained
      electronic materials. Although there was little comparable statistical data on
      usage, at the six libraries at which active selection was occurring, librarians
      and library staff felt that the collection was well used and felt that it
      provided library users with benefits such as stress relief and relaxation and
      exposure to other perspectives. CONCLUSION: Librarians and library staff at the
      libraries that undertook active selection felt that their leisure reading
      collection was worthwhile. It would be interesting for future work to focus on
      the user experience of such collections.

PMID- 24751227
TI  - Nursing staff connect libraries with improving patient care but not with
      achieving organisational objectives: a grounded theory approach.
AB  - BACKGROUND: Health organisations are often driven by specific targets defined by
      mission statements, aims and objectives to improve patient care. Health libraries
      need to demonstrate that they contribute to organisational objectives, but it is
      not clear how nurses view that contribution. OBJECTIVES: To investigate ward
      nursing staff motivations, their awareness of ward and organisational objectives;
      and their attitudes towards the contribution of health library services to
      improving patient care. METHOD: Qualitative research using focus group data was
      combined with content analysis of literature evidence and library statistics
      (quantitative data). Data were analysed using thematic coding, divided into five
      group themes: understanding of Trust, Ward and Personal objectives, use of
      Library, use of other information sources, quality and Issues. Four basic social
      psychological processes were then developed. RESULTS: Behaviour indicates low
      awareness of organisational objectives despite patient-centric motivation. High
      awareness of library services is shown with some connection made by ward staff
      between improved knowledge and improved patient care. CONCLUSION: There was a two
      tiered understanding of ward objectives and library services, based on level of
      seniority. However, evidence-based culture needs to be intrinsic in the
      organisation before all staff benefit. Libraries can actively engage in this at
      ward and board level and improve patient care by supporting organisational
      objectives.

PMID- 24751228
TI  - A checklist to assess database-hosting platforms for designing and running
      searches for systematic reviews.
AB  - BACKGROUND: Systematic reviews require literature searches that are precise,
      sensitive and often complex. Database-hosting platforms need to facilitate this
      type of searching in order to minimise errors and the risk of bias in the
      results. OBJECTIVES: The main objective of the study was to create a generic
      checklist of criteria to assess the ability of host platforms to cope with
      complex searching, for example, for systematic reviews, and to test the checklist
      against three host platforms (EBSCOhost, OvidSP and ProQuest). METHOD: The
      checklist was developed as usual review work was carried out and through
      discussion between the two authors. Attributes on the checklist were designated
      as 'desirable' or 'essential'. The authors tested the checklist independently
      against three host platforms and graded their performance from 1 (insufficient)
      to 3 (performs well). RESULTS: Fifty-five desirable or essential attributes were
      identified for the checklist. None of the platforms performed well for all of the
      attributes on the checklist. CONCLUSIONS: Not all database-hosting platforms are
      designed for complex searching. Librarians and other decision-makers who work in
      health research settings need to be aware of the different limitations of host
      platforms for complex searching when they are making purchasing decisions or
      training others.

PMID- 24751229
TI  - A comparison of searching the Cochrane library databases via CRD, Ovid and Wiley:
      implications for systematic searching and information services.
AB  - BACKGROUND: The Cochrane Library databases are available via different
      interfaces; evidence in the literature, together with anecdotal evidence, shows
      interfaces perform differently. To ensure the quality of searches, a study was
      undertaken to systematically explore the functionality of interfaces. OBJECTIVES:
      To demonstrate differences in functionality when searching the same databases
      across different interfaces; to discuss the implications this may have on
      searching; and in a wider context, to suggest a 'best match' for comparable
      searching. METHODS: Detailed cross-comparisons of a selection of search functions
      including MeSH terms, free text, proximity operators and truncation were
      undertaken in databases accessed via CRD, Wiley and Ovid. Up to three terms per
      function were selected and analysed. RESULTS: Differences were identified in the
      way searches for MeSH headings are executed, which fields are searched, how
      proximity operators perform, the word order searched and where terms are
      searched. This adds to a body of evidence demonstrating a lack of consistency in
      searching across different interfaces. CONCLUSIONS: A 'best match' for comparable
      searching is suggested. Differences between interfaces offering the same database
      content can have implications for the success of a search, on user education, and
      on database evaluation and purchasing decisions.

PMID- 24751231
TI  - International trends in health science librarianship Part 9: the UK - Scotland
      and Wales.
AB  - This is the 9th in a series of articles exploring international trends in health
      science librarianship. The previous article in this series looked at Northern
      Ireland and the Republic of Ireland. In this issue the focus is Scotland and
      Wales. There will be three or four more articles this year tracking trends in the
      Far East, Africa, South Asia and the Middle East. JM. 

PMID- 24751230
TI  - Outreach services in healthcare libraries: perceptions and impacts.
AB  - Outreach services are becoming more prevalent throughout the health library
      sector both in the UK and abroad, and they have the potential to impact on
      information support for evidence-based medicine. This article reports on a study
      which explored the perceptions of UK health library staff about the term
      'outreach' and demonstrated that a variety of services are being offered under
      this umbrella term. Whilst practitioners are also divided over the impact of
      outreach services, many of them see this as key to future service developments.
      The study was completed by Rebecca Dorsett as part of her MSc in Information and
      Library Management at Northumbria University. She was supervised by Sue Childs
      and graduated in 2012 with a Distinction. Rebecca is now due to commence a new
      role as Information Support Officer for the Ministry of Defence. AM. 

PMID- 24751232
TI  - Cinemeducation: using film as an educational tool in mental health services.
AB  - This feature looks at the benefits of using film as an educational tool for
      mental health. In particular, it presents two case studies outlining how two
      health library services successfully implemented film clubs for the purposes of
      teaching and learning for mental health. H.S. 

PMID- 24751233
TI  - Characteristics of Clostridium difficile colonization in Japanese children.
AB  - In children, asymptomatic colonization with Clostridium difficile is well known,
      but its prevalence in Japanese children is not fully understood. The objective of
      this study was to determine the colonization rate of C. difficile and to identify
      the risk factors for C. difficile colonization in Japanese children. Single fecal
      samples were prospectively collected from children hospitalized in Saitama City
      Hospital between August 1, 2012, and March 31, 2013. Samples were obtained from
      neonates, at 4-14 days after birth, and from non-neonatal children, principally
      within 2 days after admission, to determine community-associated colonization.
      The fecal samples were cultured for C. difficile, and isolated strains were
      tested for production of Clostridial toxins A/B. In 95 neonates, the colonization
      rate of C. difficile was 0%. The 251 non-neonatal children were divided into two
      subgroups, depending on the presence or absence of underlying disease. In the
      subgroup without underlying disease, the colonization rates of C. difficile and
      toxin-positive C. difficile were 21.6% and 9.0%, respectively, while in the
      subgroup with underlying disease, values were 30.8% and 23.1%, respectively. The
      proportion of toxin-positive C. difficile in all of the culture-isolated strains
      from the latter subgroup (75.0%) was statistically higher than that from the
      former subgroup (41.9%) (P = 0.049). Multivariate logistic regression analysis
      indicated an association of tube feeding with significantly higher colonization
      rates of C. difficile (Odds Ratio(OR) = 24.28; 95% confidence interval(CI)[4.70
      125.34]; P < 0.001) and toxin-positive C. difficile (OR = 8.29; 95%CI[1.87
      36.84]; P = 0.005). Further evaluations are recommended to assess the
      epidemiology and the role of C. difficile in Japanese children.

PMID- 24751234
TI  - Cytomegalovirus enteritis in immunocompetent subjects: a case report and review
      of the literature.
AB  - Cytomegalovirus (CMV) enteritis (or colitis) is generally diagnosed in
      immunocompromised patients in association with human immunodeficiency virus
      infection as well as in recipients of solid organ or hematopoietic stem cell
      transplant. CMV enteritis has been reported only sporadically in immunocompetent
      individuals. We encountered a 76-year-old woman who developed CMV enteritis
      without any previously identified immunocompromised states. An extensive
      literature review of 33 cases of CMV enteritis or colitis diagnosed in
      immunocompetent individuals, including the present case, revealed that the median
      age of the patients was 68, the accompanying symptoms were diarrhea (76%),
      abdominal pain (52%), and hematochezia or melena (27%), and that the outcome was
      generally favorable, including resolution without any treatment in 24% of the
      patients. CMV enteritis should be recognized more widely as a disease entity not
      only in immunocompromised patients but also in immunocompetent individuals,
      especially in elderly populations. 

PMID- 24751235
TI  - Antifungal susceptibility of Aspergillus fumigatus clinical isolates collected
      from various areas in Japan.
AB  - Azole resistance among clinical isolates of Aspergillus fumigatus is becoming a
      serious problem in Europe, but the status in Japan is not yet known in detail.
      The aim of this study was to determine the present status of azole resistance in
      A. fumigatus in Japan. We employed 171 clinical isolates of A. fumigatus sensu
      stricto collected from 1987 to 2008 at the Medical Mycology Research Center,
      Chiba University, Japan for azole resistance determination. Identification of all
      isolates were re-examined both from the aspect of morphology and molecular
      phylogeny. The antifungal susceptibility of these isolates was tested based on
      the CLSI M38-A2 broth microdilution method. In our collection, only 1 (0.6%) and
      2 isolates (1.2%) showed elevated MIC to voriconazole and itraconazole,
      respectively. Our study disclosed that the frequency of azole resistance in A.
      fumigatus still remains low in this collection.

PMID- 24751236
TI  - The complex choreography of transcription-coupled repair.
AB  - A quarter of a century has elapsed since the discovery of transcription-coupled
      repair (TCR), and yet our fascination with this process has not diminished.
      Nucleotide excision repair (NER) is a versatile pathway that removes helix
      distorting DNA lesions from the genomes of organisms across the evolutionary
      scale, from bacteria to humans. TCR, defined as a subpathway of NER, is dedicated
      to the repair of lesions that, by virtue of their location on the transcribed
      strands of active genes, encumber elongation by RNA polymerases. In this review,
      we will report on newly identified proteins, protein modifications, and protein
      complexes that participate in TCR in Escherichia coli and in human cells. We will
      discuss general models for the biochemical pathways and how and when cells might
      choose to utilize TCR or other pathways for repair or bypass of transcription
      blocking DNA alterations. 

PMID- 24751237
TI  - Bartonella quintana in body lice from scalp hair of homeless persons, France.

PMID- 24751238
TI  - The desire to survive: the adaptation process of adult cancer patients undergoing
      radiotherapy.
AB  - AIM: Radiotherapy is one of the primary treatment strategies for cancer. However,
      patients not only deal with the side-effects of radiotherapy, but they must also
      endure the psychological distress caused by cancer. This study explores how
      cancer patients adapt to the treatment process when receiving radiotherapy.
      METHODS: This study used a grounded theory approach, and eight in-depth
      interviews were conducted with newly diagnosed cancer patients who received
      radiotherapy as a primary treatment. RESULTS: The core category that emerged from
      this study was "the desire to survive". The categories and subcategories that
      emerged from the data include facing unknown situations (e.g. searching for
      relevant information and decision-making considerations, and listening to
      healthcare professionals' suggestions), experiencing the pain of treatment (e.g.
      tolerating side-effects, tolerating inconvenience during the treatment, accepting
      support during the treatment, and adjusting lifestyles), and chances to extend
      life (e.g. accepting fate, determination to undergo the treatment, and adjusting
      negative emotions). CONCLUSION: The study results provide a better understanding
      of the experiences of cancer patients undergoing radiotherapy. Healthcare
      professionals should provide effective medical management for side-effects and
      psychological support to cancer patients during the journey of radiotherapy.

PMID- 24751240
TI  - Determination of the thermo-mechanical properties in starch and starch/gluten
      systems at low moisture content - a comparison of DSC and TMA.
AB  - The impact of heating rate on the glass transition (Tg) and melting transitions
      observed by differential scanning calorimetry (DSC) on starch and a starch/gluten
      blend (80:20 ratio) at low moisture content was examined. The results were
      compared to those determined by thermo-mechanical analysis (TMA). Comparison with
      dynamic mechanical thermal analysis (DMTA) and phase transition analysis (PTA) is
      also discussed. Higher heating rates increased the determined Tg as well as the
      melting peak temperatures in both starch and the starch/gluten blend. A heating
      rate of 5 degrees C/min gave the most precise value of Tg while still being
      clearly observed above the baseline. Tg values determined from the first and
      second DSC scans were found to differ significantly and retrogradation of starch
      biopolymers may be responsible. Tg values of starch determined by TMA showed good
      agreement with DSC results where the Tg was below 80 degrees C. However, moisture
      loss led to inaccurate Tg determination for TMA analyses at temperatures above 80
      degrees C.

PMID- 24751239
TI  - Biochemical characterization of proline dehydrogenase in Arabidopsis
      mitochondria.
AB  - Proline has multiple functions in plants. Besides being a building block for
      protein biosynthesis proline plays a central role in the plant stress response
      and in further cellular processes. Here, we report an analysis on the integration
      of proline dehydrogenase (ProDH) into mitochondrial metabolism in Arabidopsis
      thaliana. An experimental system to induce ProDH activity was established using
      cell cultures. Induction of ProDH was measured by novel photometric activity
      assays and by a ProDH in gel activity assay. Effects of increased ProDH activity
      on other mitochondrial enzymes were systematically investigated. Activities of
      the protein complexes of the respiratory chain were not significantly altered. In
      contrast, some mitochondrial dehydrogenases had markedly changed activities.
      Activity of glutamate dehydrogenase substantially increased, indicating
      upregulation of the entire proline catabolic pathway, which was confirmed by co
      expression analyses of the corresponding genes. Furthermore, activity of d
      lactate dehydrogenase was increased. d-lactate was identified to be a competitive
      inhibitor of ProDH in plants. We suggest that induction of d-lactate
      dehydrogenase activity allows rapid upregulation of ProDH activity during the
      short-term stress response in plants.

PMID- 24751241
TI  - Improved probiotic viability in stress environments with post-culture of alginate
      chitosan microencapsulated low density cells.
AB  - In this study, probiotics (Saccharomyces cerevisiae Y235) were entrapped in
      alginate-chitosan microcapsules by emulsification/internal gelation technique.
      Two different encapsulation patterns were established as directly entrapped high
      density cells (dEHDC) and entrapped low density cells with culture (ELDCwc). The
      performance of microencapsulated cells, with free cells (FC) as control, was
      investigated against sequential stress environments of freeze-drying, storage,
      and simulated gastrointestinal fluids. After being freeze-dried without
      cryoprotectant, the survival rate of ELDCwc (14.33%) was significantly higher
      than 10.00% of dEHDC, and 0.05% of FC. The lower temperature (-20 degrees C) and
      ELDCwc pattern were beneficial for keeping viable cells at 7.00 logCFU g(-1)
      after 6 months. Furthermore, the ELDCwc microcapsule maintained viable cells of
      6.29 logCFU g(-1) after incubation in SGF and SIF. These studies demonstrated
      that the pattern of entrapped low density cells with culture was an effective and
      superior technique of resisting harmful stress environments.

PMID- 24751242
TI  - Polysaccharides isolated from Digenea simplex inhibit inflammatory and
      nociceptive responses.
AB  - Polysaccharides (PLS) have notably diverse pharmacological properties. In the
      present study, we investigated the previously unexplored anti-inflammatory and
      antinociceptive activities of the PLS fraction isolated from the marine red alga
      Digenea simplex. We found that the PLS fraction reduced carrageenan-induced edema
      in a dose-dependent manner, and inhibited inflammation induced by dextran,
      histamine, serotonin, and bradykinin. The fraction also inhibited neutrophil
      migration into both mouse paw and peritoneal cavity. This effect was accompanied
      by decreases in IL1-beta and TNF-alpha levels in the peritoneal fluid. Pre
      treatment of mice with PLS (60 mg/kg) significantly reduced acetic acid-induced
      abdominal writhing. This same dose of PLS also reduced total licking time in both
      phases of a formalin test, and increased latency in a hot plate test. Therefore,
      we conclude that PLS extracted from D. simplex possess anti-inflammatory and
      antinociceptive activities and can be useful as therapeutic agents against
      inflammatory diseases.

PMID- 24751243
TI  - Thermosensitive in situ hydrogel based on the hybrid of hyaluronic acid and
      modified PCL/PEG triblock copolymer.
AB  - In this work, a new hydrogel was constructed using poly(E-caprolactone-co-1,4,8
      trioxa[4.6]spiro-9-undecanone)-poly(ethylene glycol)-poly(E-caprolactone-co-1,4,8
      trioxa[4.6]spiro-9-undecanone) tri-block copolymers (PECT) with hyaluronic acid
      (HA) in order to expand application scopes of PECT hydrogel. The rheological and
      sol-gel phase transition behaviors were investigated by rheometer and test tube
      inversion method, and the interior morphologies of hydrogel systems were observed
      by scanning electron microscope (SEM). With the introduction of HA, certain
      properties of PECT hydrogel, such as viscosity and morphology, have present
      trends with regularity. Furthermore, with the participation of HA, the
      degradation and release of acetylsalicylic acid was slightly affected, however,
      the drug release mechanism of hydrogel has not been changed. PECT/HA hydrogel is
      confirmed to be non-toxic through a test to NIH3T3 cells. In conclusion, blending
      with HA is a feasible and safe method to tune properties of PECT hydrogel.

PMID- 24751244
TI  - Multilayers of cellulose derivatives and chitosan on nanofibrillated cellulose.
AB  - The aim of this work was to study the effect of solution conditions and
      polysaccharide structure on their Layer-by-Layer (LbL) deposition on
      nanofibrillated cellulose (NFC). Multilayer build-up of cellulose derivatives and
      chitosan on NFC model surfaces was studied using Quartz Crystal Microbalance with
      Dissipation (QCM-D) and Colloidal Probe Microscopy (CPM). The type of cationic
      polysaccharide was found to significantly affect the multilayer build-up and
      surface interactions. Cationic cellulose derivative quaternized hydroxyethyl
      cellulose ethoxylate (HECE) formed highly water-swollen layers with carboxymethyl
      cellulose (CMC), and the build-up was markedly influenced by both the ionic
      strength and pH. The ionic strength did not significantly influence the
      multilayer build-up of chitosan-CMC system, and adsorbed chitosan layers
      decreased the viscoelasticity of the system. Based on the results, it was also
      confirmed that electrostatic interaction is not the only driving force in case of
      the build-up of polysaccharide multilayers on nanofibrillated cellulose. 

PMID- 24751245
TI  - Antioxidant properties of different molecular weight polysaccharides from
      Athyrium multidentatum (Doll.) Ching.
AB  - Different molecular weight polysaccharides were prepared by degradation of
      polysaccharides extracted from Athyrium multidentatum (Doll.) Ching rhizome (CPA)
      with hydrogen peroxide and ascorbic acid. Four low molecular polysaccharides
      derivatives (CPA-1, CPA-2, CPA-3 and CPA-4) were successfully obtained and had
      their antioxidant activities investigated employing various established in vitro
      systems. All CPA derivatives showed pronounced antioxidant activity, and had
      stronger antioxidant ability than CPA in certain tests. CPA-1 exhibited the
      strongest scavenging ability on 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical
      among all samples, and the IC50 value was 25 MUg/mL. CPA-2 possessed the highest
      scavenging ability against superoxide radical at 200 MUg/mL. The scavenging
      activity of CPA-4 on hydroxyl radical was higher than CPA from 120 to 200 MUg/mL.
      The mechanism on influence the antioxidant activity of CPA and its degraded
      derivatives was indicated.

PMID- 24751246
TI  - Novel and diverse fine structures in LiCl-DMSO extracted apple hemicelluloses.
AB  - Hemicelluloses are key polysaccharides in the regulation of the mechanical
      properties of plant cell walls during organ development and in fruit texture.
      Their diverse compositions and structures are partially known, in particular with
      regard to their function in cell walls. To that end, apple hemicelluloses were
      sequentially extracted by DMSO doped by LiCl followed by potassium hydroxide. The
      weakly bounded hemicelluloses in the LiCl-DMSO soluble extract were fractionated
      by ion exchange (AEC) and size exclusion (SEC) chromatographies. The structure of
      all the extracts and fractions was established by enzymatic fingerprinting using
      beta-glucanase, beta-mannanase and beta-xylanase. Molecular weight of the
      fraction was established by HPSEC. MS as well as HPAEC analyses of the enzyme
      digests revealed the remarkable diversity of apple hemicelluloses. Different
      xyloglucan (XyG), galactoglucomannan (GgM) and glucuronoarabinoxylan were
      isolated along the extraction and fractionation process. All LiCl-DMSO soluble
      fractions were acetyl-esterified. Besides, the LiCl-DMSO soluble XyG differed
      from the 4M KOH extracted one essentially on the basis of its molecular weight.
      At least two populations differing in their content and distribution of glucose
      and mannose composed GgM. Moreover, galactose ramifications occurred on mannose
      blocks in the glucose rich fraction. These results open the way for future
      studies on the complex structure-function relationship of hemicelluloses in plant
      cell walls. 

PMID- 24751247
TI  - Antioxidant activity and characterization of antioxidant polysaccharides from
      pine needle (Cedrus deodara).
AB  - A novel antioxidant polysaccharide (APC) was isolated and characterized from pine
      needles of Cedrus deodara with the evaluation of its in vitro antioxidant
      activity. According to gel filtration chromatography, high performance size
      exclusion chromatography, gas chromatography-mass spectrometry, partial acid
      hydrolysis, periodic acid oxidation, Smith degradation and methylation analysis,
      APC was observed to be an acidic heteropolysaccharide (composed of glucose,
      arabinose, mannose and xylose in a molar ratio of 45.84:1:2.35:1.73) with the
      molecular weight of 1.53*10(4)Da, and the backbone was mainly composed by
      glucose, mannose and xylose in the form of (1->4) linked. Meanwhile, APC
      exhibited the remarkable antioxidant activity to scavenge free radicals and
      inhibit the oxidative injury of DNA and cells. The present results suggested that
      APC could be a potential antioxidant agent for preparing functional foods and
      nutraceuticals applied in food and pharmaceutical industries.

PMID- 24751248
TI  - Recycling of textile dye using double network polymer from sodium alginate and
      superabsorbent polymer.
AB  - Double network polymers (DNP) of different compositions were photosynthesized
      using sodium alginate (NaAlg) and superabsorbent polymer (SAP). They were
      characterized by FT-IR, thermal stability (TG), morphology by scanning electron
      microscopy (SEM), and its mechanical properties were also evaluated for their dye
      adsorption-desorption characteristics via adsorption isotherms at different
      temperature and pH values. The spectrophotometric determination of adsorbed dye
      indicated that the maximum dye uptake in column mode was 439 mg/g. The nearly
      identical visible absorption spectra of the fabrics dyed with virgin and
      recovered dyes indicated that the recovered dye retained its structural stability
      during column recovery and the dyed fabrics possess good color fastness
      properties. Dye adsorption kinetic and de-sorption mechanism were found to be
      pseudo-first-order and non-Fickian, respectively. The adsorption showed best fit
      for Langmuir adsorption isotherm. The changes in the thermodynamic parameters
      namely Gibbs free energy (DeltaG degrees ), entropy (DeltaS degrees ) and
      enthalpy (DeltaH degrees ) for the dye-adsorbent systems inferred that the
      adsorption process was spontaneous and exothermic.

PMID- 24751249
TI  - Plasticizing effect of ionic liquid on cellulose acetate obtained by melt
      processing.
AB  - Cellulose acetate (CA) plasticized by 1-butyl-3-methylimidazolium chloride
      (BMIMCl) and with diethylphtalate (DEP) was obtained by melt processing at 150
      degrees C. The effect and the interaction of ionic liquid with the cellulose
      acetate and their influence on structural, thermo-mechanical, rheological and
      tensile properties of CA materials were investigated. Ionic liquid (BMIMCl) has
      shown a good plasticization and more efficient destruction of the crystalline
      structure of cellulose acetate than the DEP plasticized CA. BMIMCl interacts
      intensively with CA molecules due to the pronounced van der Waals interactions,
      hydrogen bonding and electrostatic nature of ionic liquid. The tensile test and
      the low Young's modulus for plasticized CA suggest a strong reduction of the
      interaction between the CA chains due to the presence of the ionic liquid. 

PMID- 24751250
TI  - Preparation and properties of carboxymethyl cellulose/layered double hydroxide
      bionanocomposite films.
AB  - Solution casting method was employed for preparing of carboxymethyl
      cellulose/layered double hydroxide (CMC-LDH) bionanocomposite films with LDH
      content ranged from 0 to 8 wt%. The synthesized nanocomposite films were
      characterized using FTIR, XRD, TEM and SEM analytical methods. XRD and TEM
      analysis revealed a partially exfoliated structure for nanocomposites with LDH
      content up to 3 wt%. However, for LDH contents higher than 3 wt%, nanocomposites
      formed an intercalated structure. Incorporation of LDH significantly decreased
      water vapor permeability (WVP) of the bionanocomposite films up to 37%. Addition
      of the LDHs into the CMC matrix is accompanied by a decrease in the film
      transparency. Mechanical properties of CMC-based films were improved
      significantly by addition of LDH particles. CMC-LDH nanocomposite film with 3 wt%
      LDH showed a 148 and 143% increase in the tensile strength and tensile modulus,
      as well as a 62% decrease in elongation in comparison with the pure CMC film.

PMID- 24751251
TI  - Genipin-crosslinked chitosan/poly-L-lysine gels promote fibroblast adhesion and
      proliferation.
AB  - Chitosan blends have been widely investigated to create biomaterials with
      desirable physicochemical and biological properties for tissue engineering
      applications. A recurring difficulty, however, has been to maintain their
      stability in an aqueous environment. The rationale behind this study was to
      demonstrate that genipin crosslinking can improve and maintain the stability of
      chitosan/poly-l-lysine (PLL) blends. Four gel formulations were prepared by
      varying the weight ratios of chitosan and PLL. Electron microscopy revealed that
      genipin crosslinking provided a more homogenous gel surface compared to
      uncrosslinked gels. Moreover, it was discovered that 3h was sufficient to
      stabilize the gels. In vitro studies using fibroblasts demonstrated that genipin
      crosslinked gels enhanced fibroblasts' attachment as compared to uncrosslinked
      gels. Moreover, cell viability was significantly improved by 1.6 times on 60:40
      gels, and 6.5 times on 50:50 gels after crosslinking. Finally, proliferation was
      enhanced up to 5 times on 60:40 gels. 

PMID- 24751252
TI  - Cellulase-assisted extraction and antioxidant activity of polysaccharides from
      Rhizoma imperata.
AB  - In this study, the cellulase-assisted extraction and antioxidant activity of the
      polysaccharides from Rhizoma imperata were investigated. To improve the yield of
      R. Imperata polysaccharides (RPs), the extraction conditions were optimized as
      follows: time, 69.48 min; temperature, 45.36 degrees C; pH, 4.58; cellulase
      amount, 1,200 U/g. Under these optimum conditions, the yield of RPs reached 0.67%
      (w/w), and was higher than that of the traditionally aqueous extraction method.
      The sugar content in the RPs product reached up to 93.25% (w/w). The RPs product
      has high antioxidant activity including hydroxyl radical scavenging activity and
      2,2-diphenyl-beta-picrylhydrazyl radical scavenging activity at the concentration
      of 100mg/mL.

PMID- 24751253
TI  - Preparation, characterization, mechanical and barrier properties investigation of
      chitosan-clay nanocomposites.
AB  - In the current study the effect of dilution of chitosan acetate solution and of
      the use of a reflux-solution method on the morphology, the mechanical and water
      barrier properties of chitosan based nanocomposites is being investigated. Two
      series of nanocomposite films from two chitosan acetate solutions with 2 w/v% and
      1 w/v% in chitosan were prepared, with 3, 5 and 10 wt% Na-montmorillonite (NaMMT)
      and/or 30 wt% glycerol. Intercalation of NaMMT was more effective in films based
      on 2 w/v% solutions which presented decreased hydrated crystallinity. Upon NaMMT
      addition an enhancement was found in stiffness and strength (up to 100%) and a
      remarkable decrease in the elongation at break (up to 75%) and water vapor
      permeability (WVP) (up to 65%). This enhancement was less pronounced in 1 w/v%
      systems. Addition of glycerol had a negative effect on the stiffness, strength
      and WVP, and a positive effect on the elongation at break and the absorbed water.
      Compared with the conventional solution cast method, the reflux treatment led to
      a significant improvement of the tested properties of nanocomposite films.

PMID- 24751254
TI  - Mutations enhance beta-cyclodextrin specificity of cyclodextrin
      glycosyltransferase from Bacillus circulans.
AB  - The effects of amino acid residue at position 31 in the neighborhood of calcium
      binding site I (CaI) on product specificity of cyclodextrin glycosyltransferase
      (EC 2.4.1.19, CGTase) were investigated by replacing Ala31 in the CGTase from
      Bacillus circulans STB01 with arginine, proline, threonine, serine and glycine.
      The results showed that the mutations A31R, A31P, and A31T resulted in the
      increases in beta-cyclodextrin-forming activity and beta-cyclodextrin production,
      indicating that these mutations enhanced beta-cyclodextrin specificity of the
      CGTase. Especially the mutant A31R displayed approximately 26% increase in beta
      cyclodextrin production with a concomitant 41% decrease in alpha-cyclodextrin
      production when compared to the wild-type CGTase. Thus, it was much more suitable
      for the industrial production of beta-cyclodextrin than the wild-type enzyme. The
      enhanced beta-cyclodextrin specificity of the mutants might be a result of
      stabilizing CaI, which also suggested that CaI might play an important role in
      cyclodextrin product specificity of CGTase. 

PMID- 24751255
TI  - Universality and specificity in molecular orientation in anisotropic gels
      prepared by diffusion method.
AB  - Molecular orientation in anisotropic gels of chitosan, Curdlan and DNA obtained
      by dialysis of those aqueous solutions in gelation-inducing solutions was
      investigated. In this diffusion method (or dialysis method), the gel formation
      was induced by letting small molecules diffuse in or out of the polymer solutions
      through the surface. For the gels of DNA and chitosan, the polymer chains aligned
      perpendicular to the diffusion direction. The same direction of molecular
      orientation was observed for the Curdlan gel prepared in the dialysis cell. On
      the other hand, a peculiar nature was observed for the Curdlan gel prepared in
      the dialysis tube: the molecular orientation was perpendicular to the diffusion
      direction in the outermost layer of the gel, while the orientation was parallel
      to the diffusion direction in the inner translucent layer. The orientation
      parallel to the diffusion direction is attributed to a small deformation of the
      inner translucent layer caused by a slight shrinkage of the central region after
      the gel formation. At least near the surface of the gel, the molecular
      orientation perpendicular to the diffusion direction is a universal
      characteristic for the gels prepared by the diffusion method. 

PMID- 24751256
TI  - Amylopectin-g-poly(N-vinyl-2-pyrrolidone): synthesis, characterization and in
      vitro release behavior.
AB  - In the present study, amylopectin-g-poly(N-vinyl-2-pyrrolidone) was synthesized
      by UV-assisted grafting reactions. The effect of concentrations of amylopectin, N
      vinyl-pyrrolidone and ammonium persulfate on the % grafting efficiency was
      studied using 3-factor, 2-level factorial experimental design. The graft co
      polymer was characterized by Fourier-transform infrared spectroscopy (FT-IR),
      differential scanning calorimetry (DSC), X-ray diffraction (XRD) and scanning
      electron microscopy (SEM) studies. The concentrations of amylopectin, N-vinyl-2
      pyrrolidone and ammonium persulfate were found to exert a significant synergistic
      effect on grafting efficiency. The optimized batch of graft co-polymer prepared
      using concentration of amylopectin (4%), N-vinyl-2-pyrrolidone (2%) and ammonium
      persulfate (10 mmol/L) had 83.16% grafting efficiency. On comparative evaluation
      of films of amylopectin-g-poly(N-vinyl-pyrrolidone) with amylopectin, the graft
      co-polymer film provided a prolonged release following Higuchi square release
      kinetics.

PMID- 24751257
TI  - Synthesis, characterization and anti-tubercular activity of ferrocenyl hydrazones
      and their beta-cyclodextrin conjugates.
AB  - A series of ferrocenyl hydrazones and their beta-cyclodextrin (CD) inclusion
      complexes were prepared and evaluated for antitubercular activity under low and
      high iron conditions. The inclusion complexes were characterized by Fourier
      Transform Infrared (FTIR), Differential Scanning Calorimetry (DSC), Powder X-ray
      Diffraction (PXRD), (1)H NMR, Scanning Electron Microscopy (SEM) and Cyclic
      Voltammetric (CV) studies. The inclusion complexes exhibited improved aqueous
      solubility as well as enhanced hydrolytic and thermal stability. They were also
      found to exhibit greater antitubercular activity than the parent ferrocenyl
      hydrazones against Mycobacterium tuberculosis under high iron conditions. When
      grown under low iron conditions these compounds exhibited lower activity
      suggesting requirement of iron-dependant peroxidase activation.

PMID- 24751258
TI  - Surface modification of cotton fabrics for antibacterial application by coating
      with AgNPs-alginate composite.
AB  - In recent years nano-sized particles have been focused on bacteriostasis. We
      investigated antimicrobial activities by applying AgNPs-alginate composite on
      cotton fabric, using a simple one-step rapid synthetic route by reduction of
      silver nitrate using alkali hydrolyzed alginate solution which acts as both
      reducing and capping agent. FTIR spectra, color coordinates, silver content,
      silver release percent and SEM images of treated fabric samples confirmed the
      successful physical deposition of AgNPs-alginate composite on the fabric. The
      treated fabrics demonstrated an excellent antibacterial activity against the
      tested bacteria, Escherichia coli, Staphylococcus aureus and Pseudomonas
      aeruginosa. A slight decrease in the antibacterial feature of the cotton fabrics
      was observed after successive washings. However, an efficient antibacterial
      activity still remained on the fabrics.

PMID- 24751259
TI  - A new method for determining the relative crystallinity of chickpea starch by
      Fourier-transform infrared spectroscopy.
AB  - A new method for determining the relative crystallinity (RC) of chickpea starch
      was developed by using Fourier-transform infrared (FT-IR) spectroscopy, based on
      hypotheses as described as follows: there is a Gaussian holocrystalline-peak
      (HCP) in the 800-1,300 cm(-1) region of FT-IR spectrum of starch which is divided
      into amorphous region and crystalline region; the crystalline region of HCP is
      the overlap of the HCP and the FT-IR spectrum of starch; the RC of starch is the
      ratio of the area of crystalline region to the area of HCP. It was found that
      there was no significant difference between the RC determined by FT-IR method and
      that determined by X-ray diffraction (XRD) method. The intra-class correlation
      coefficient was 0.998 (p=0.000, n=9) and the 95% confidence interval was 0.992
      1.000 for the RC determined by XRD and FT-IR. Furthermore, the developed method
      showed good repeatability (coefficient of variation (CV), 1.1-2.9%) and good
      intermediate precision (CV, 2.8%).

PMID- 24751260
TI  - Impact of purification and fractionation process on the chemical structure and
      physical properties of locust bean gum.
AB  - Crude locust bean gum (CLBG) was purified and fractionated into two parts: the
      first was obtained by solubilization in water at 25 degrees C (GM25) and the
      second consisted in a further extraction at 80 degrees C on the residual
      impoverished fraction (GM80). The complete structural characterization has shown
      that GM80 possessed relatively longer chain lengths than GM25, a slightly lower
      degree of galactose substitution and a somewhat sharper galactosyl distribution
      in substituted and unsubstituted regions. A physical behavior analysis was
      carried out on solubilization kinetics, viscosity, viscoelasticity and formation
      of associated gels with xanthan or carrageenan. The average structure of GM80
      generated larger intra-chain, inter-chain and inter-molecular interactions,
      resulting in the appearance of a stronger network. Small structural differences
      therefore generated very different physical behaviors. This study thus allowed to
      establish, in a precise and complete manner, fractionation-purification-structure
      function relationships of galactomannans extracted from carob.

PMID- 24751261
TI  - Nano-titania-crosslinked chitosan composite as a superior sorbent for antimony
      (III) and (V).
AB  - Removal of radioactive antimony, especially at low levels, is a difficult problem
      faced by nuclear power plants all over the world. Further, antimony is classified
      as a pollutant of priority importance by the United States and the European
      environmental protection agencies. Chitosan, a biopolymer well known for its
      sorption properties, can also serve as a stable matrix for inorganic sorbents
      such as titania on crosslinking. A robust high performing sorbent for antimony,
      in the form of stable beads, has been prepared using nano-TiO2 and chitosan.
      Raman spectra of the beads confirmed the incorporation of nano-TiO2 in the
      chitosan matrix. The sorbent exhibited complete sorption of antimony from aqueous
      solutions with antimony concentrations ranging from as low as 150 ppb to as high
      as 120 ppm. The sorption dependence on equilibrium pH has been investigated. The
      beads have been shown to be effective sorbent of antimony in both +3 and +5
      oxidation states. The sorption properties of the beads were attributed to the
      TiO2 component present in the beads, while the crosslinked chitosan provided
      strong matrix and influenced the formation of much needed stable spherical beads
      suitable for real life large scale applications. The beads exhibited high
      sorption efficiency in the column mode, and were found to be physically stable at
      a flow rate of one bed volume per minute.

PMID- 24751262
TI  - Wet spinning of fibers made of chitosan and chitin nanofibrils.
AB  - Biocompatible and bioresorbable composite fibers consisting of chitosan filled
      with anisotropic chitin nanofibrils with the length of 600-800 nm and cross
      section of about 11-12 nm as revealed by SEM and XRD were prepared by
      coagulation. Both chitin and chitosan components of the composite fibers
      displayed preferred orientations. Orientation of chitosan molecules induced by
      chitin nanocrystallites was confirmed by molecular modeling. The incorporation of
      0.1-0.3 wt.% of chitin nanofibrils into chitosan matrix led to an increase in
      strength and Young modulus of the composite fibers.

PMID- 24751263
TI  - Effect of gums on the rheological characteristics and microstructure of acid
      induced SPI-gum mixed gels.
AB  - The effect of addition of xanthan gum (XG) and guar gum (GG) on the rheological
      properties and microstructure of glucono-delta-lactone induced soy protein
      isolate (SPI)-XG gels and SPI-GG gels was investigated using steady and dynamic
      rheological tests, creep-recovery and confocal laser scanning microscopy (CLSM).
      Results showed that the apparent viscosity of SPI-gum (XG, GG) mixed solutions
      increased with the increase in the gum (XG, GG) concentration. The storage (G')
      and loss (G") moduli of SPI-gum (XG, GG) mixed gels increased in the presence and
      increase in the gum (XG, GG) concentration. The Burger's model fitted the creep
      recovery data well (R(2)>0.919) and showed that both the instantaneous and
      equilibrium (retarded) elastic components of this model increased with the
      increase in SPI and gum concentrations. The proportion occupied by gum in mixed
      gels was found to increase with the increase in the concentration of gums which
      increased the density of protein aggregates in the mixed gels.

PMID- 24751264
TI  - Electrospun nanofibrous chitosan membranes modified with polyethyleneimine for
      formaldehyde detection.
AB  - Here we describe a formaldehyde sensor fabricated by coating polyethyleneimine
      (PEI) functionalized chitosan nanofiber-net-binary structured layer on quartz
      crystal microbalance (QCM). The chitosan fibrous substrate comprising nanofibers
      and spider-web-like nano-nets constructed by a facile electro-spinning/netting
      process provided an ideal structure for the uniform PEI modification and sensing
      performance enhancement. Benefiting from the fascinating nanostructure, abundant
      primary amine groups of PEI, and strong adhesive force to the QCM electrode of
      PEI-chitosan membranes, the developed formaldehyde sensor presented rapid
      response and low detection limit (5 ppm) at room temperature. These findings have
      important implications in fabricating multi-dimensional nanostructures on QCM for
      gas sensing and chemical analysis.

PMID- 24751265
TI  - Physicochemical properties and digestibility of common bean (Phaseolus vulgaris
      L.) starches.
AB  - Physicochemical properties and digestibility of pinto bean, red kidney bean,
      black bean and navy bean starches were analyzed. All the common bean starches had
      oval and spherical granules with average diameter of 25.3-27.4 MUm. Amylose
      contents were 32.0-45.4%. Black bean starch showed the highest peak viscosity,
      breakdown, final viscosity and setback, whereas red kidney bean starch showed the
      lowest pasting temperature, peak viscosity, breakdown, and setback. Pinto bean
      starch showed the highest onset and peak gelatinization temperatures, and the
      lowest gelatinization temperature range; whereas navy bean starch exhibited the
      lowest values. Amylopectin of red kidney bean had the highest molecular weight
      (Mw) and z-average gyration radius (Rz), whereas black bean amylopectin had the
      lowest values of Mw and Rz. The proportions of DP 6-12, DP 13-24, DP 25-36, and
      DP >= 37 and average branch-chain lengths were 23.30-35.21%, 47.79-53.53%, 8.99
      12.65%, 6.39-13.49%, and 17.91-21.56, respectively. All the native bean starches
      were highly resistant to enzyme digestion.

PMID- 24751266
TI  - Removal of metal ions from water using nanohydrogel tragacanth gum-g
      polyamidoxime: isotherm and kinetic study.
AB  - A new biosorbent was prepared by grafting polyacrylonitrile onto iranian
      tragacanth gum (ITG), a naturally and abundantly available polysaccharide, and
      subsequent amidoximation in the presence of hydroxylamine hydrochloride. This
      nanohydrogel with amidoxime functional groups [C(NH2)NOH], named polyamidoxime-g
      tragacanth (ITG-g-PAO), was characterized and used for the removal of metal ions
      from aqueous solution. The effect of pH, agitation time, concentration of
      adsorbate and amount of adsorbent on the extent of adsorption was investigated.
      The experimental data were analyzed by four isotherms and kinetics equations, and
      the results were fitted well with the Temkin isotherm and pseudo-second-order
      model. The maximum adsorption capacities (Qm) of ITG-g-PAO as obtained from
      Langmuir adsorption isotherm were found to be 100.0, 76.92, 71.42 and 66.67 (mgg(
      1)) for the adsorption of metal ions in order of Co(II)>Zn(II)>Cr(III)>Cd(II).
      The experimental results demonstrate that the above selective order of adsorption
      capacity is due to formation of stable chelating ring between the bidentate
      amidoxime ligand and metal ion.

PMID- 24751267
TI  - Molecular weight, chain profile of rice amylopectin and starch pasting
      properties.
AB  - Differences in fine structure, average molecular size of amylopectin (AP) as well
      as clarity of the AP solution from indica waxy rice and high amylose (HAM) rice
      were examined. Despite similar amylose content (AM), rice starches displayed
      different pasting properties. Waxy APs had higher values of both number-average
      and weight-average molecular weight (Mn- and Mw-) but lower values of intrinsic
      viscosity [eta], compared to HAM APs. HAM APs had higher values of average chain
      length (CL-), average external chain length (ECL-), and a proportion of DP >= 37.
      Statistical correlations of mol proportions of debranched AP, branching
      parameters, and molecular weight of AP were calculated. The study showed that
      starch pasting properties and clarity of AP solutions were influenced by
      molecular weight and branching characteristics of AP.

PMID- 24751268
TI  - Enhanced water-solubility and mucoadhesion of N,N,N-trimethyl-N-gluconate-N
      homocysteine thiolactone chitosan.
AB  - A water-soluble chitosan with improved mucoadhesion was prepared by modifying
      19.4% of the amine groups of chitosan to trimethylammonium and conjugation of
      gluconolactone (GLU) and homocysteine thiolactone (HT) onto the remaining amine
      groups of the chitosan backbone. The derived trimethyl-gluconate-HT-chitosan (TM
      GN-HT-chitosan) was confirmed by Fourier Transform Infrared spectroscopy, NMR and
      thermogravimetric analysis. The total thiol and disulfide group level on the TM
      GN-HT-chitosan were 17.96 +/- 0.03 and 7.36 +/- 0.03 MUmol/g, respectively. The
      water solubility of the TM-GN-HT-chitosan conjugate was 79.0 +/- 0.15%, more than
      that of TM-chitosan and chitosan, with an enhanced solubility over a broad pH
      range ranging from 85.6 +/- 10.4% to 58.5+/-1.1% maximal solubility at pH 2 to
      11. Finally, TM-GN-HT-chitosan showed a nearly ~9.5-, 5.0- and 5.6-fold higher
      mucoadhesiveness than chitosan at pH 1.2, 4.0 and 6.4, respectively, and was
      optimal at pH 4.0.

PMID- 24751269
TI  - Porous starch/cellulose nanofibers composite prepared by salt leaching technique
      for tissue engineering.
AB  - Starch/cellulose nanofibers composites with proper porosity pore size, mechanical
      strength, and biodegradability for cartilage tissue engineering have been
      reported in this study. The porous thermoplastic starch-based composites were
      prepared by combining film casting, salt leaching, and freeze drying methods. The
      diameter of 70% nanofibers was in the range of 40-90 nm. All samples had
      interconnected porous morphology; however an increase in pore interconnectivity
      was observed when the sodium chloride ratio was increased in the salt leaching.
      Scaffolds with the total porogen content of 70 wt% exhibited adequate mechanical
      properties for cartilage tissue engineering applications. The water uptake ratio
      of nanocomposites was remarkably enhanced by adding 10% cellulose nanofibers. The
      scaffolds were partially destroyed due to low in vitro degradation rate after
      more than 20 weeks. Cultivation of isolated rabbit chondrocytes on the fabricated
      scaffold proved that the incorporation of nanofibers in starch structure improves
      cell attachment and proliferation.

PMID- 24751270
TI  - A systematic analysis of DMTMM vs EDC/NHS for ligation of amines to hyaluronan in
      water.
AB  - The activation of carboxyl groups with N-(3-dimethylaminopropyl)-N'
      ethylcarbodiimide hydrochloride and N-hydroxysuccinimide (EDC/NHS) for amide
      formation is the standard method for amine ligation to hyaluronan (HA), and a
      very well established wide-ranging bioconjugation method. In this paper we
      compare 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride
      (DMTMM) to EDC/NHS activation chemistry for HA ligation using an array of
      substrates including small, large and functional molecules. For all the
      substrates tested DMTMM yields were superior at parity of feed ratio. DMTMM
      chemistry resulted effective also in absence of pH control, which is essential
      for EDC/NHS conjugation. Overall our results demonstrate that DMTMM is more
      efficient than EDC/NHS for ligation of amines to HA and does not require accurate
      pH control or pH shift during the reaction to be effective. DMTMM-mediated
      ligation is a new promising chemical tool to synthesize HA derivatives for
      biomedical and pharmaceutical applications. 

PMID- 24751271
TI  - Extraction, characterization and antioxidant activities of polysaccharides from
      E. corneum gigeriae galli.
AB  - In the present study, optimization of enzyme-assisted extraction,
      characterization and antioxidant activities in vitro of polysaccharides from
      Endothelium corneum gigeriae galli (PEGG) were investigated. It was found that
      the optimum extraction conditions were determined as follows: extraction
      temperature 87.0 degrees C, extraction time 177.0 min, enzyme concentration
      1.65%, enzymatic hydrolysis time 141.0 min, liquid-to-solid ratio 20, enzymatic
      hydrolysis temperature 55 degrees C and enzymatic hydrolysis pH 3.6. Under these
      conditions, the experimental yield of polysaccharides was 5.08%. In addition,
      PEGG had a relatively high sulfate radical content. PEGG was composed of
      rhamnose, fucose, mannose, glucose and galactose, with molar percentages of 13.1,
      4.5, 72.8 and 9.6%, respectively. The average molecular weight was 83 kDa. And
      there were infrared characteristic absorption peaks of polysaccharides in the FT
      IR spectroscopy of PEGG. For antioxidant activities in vitro, PEGG showed
      possessed strong hydroxyl radical scavenging, Fe(2+) chelating and lipid
      peroxidation inhibitory activities.

PMID- 24751273
TI  - An attenuated total reflectance mid infrared (ATR-MIR) spectroscopy study of
      gelatinization in barley.
AB  - The aim of this study was to evaluate the use of attenuated total reflectance and
      mid infrared (ATR-MIR) spectroscopy and to understand the gelatinization and
      retro-gradation of flour barley samples and the relationship with malting
      quality. Samples were sourced from two commercial barley varieties exhibiting
      high hot water extract (HWE) namely Navigator (n=8), and Admiral (n=8). Samples
      were analysed using the Rapid Visco Analyser (RVA) and ATR-MIR analysis. These
      results showed that ATR-MIR spectroscopy is capable of characterising gel samples
      derived from barley flour samples having different malting characteristics.
      Infrared spectra can effectively represent a 'fingerprint' of the sample being
      analysed and can be used to simplify and reduce analytical times in the routine
      methods currently used. 

PMID- 24751272
TI  - Nasal polysaccharides-glucose regulator microparticles: optimization,
      tolerability and antidiabetic activity in rats.
AB  - The aim of the present study was to load the post-prandial glucose regulator,
      repaglinide (REP), on spray dried mucoadhesive microparticles (MPs) comprising
      anionic polysaccharides. The formulation parameters of the polysaccharides-REP
      spray dried powders (SDP) namely, polysaccharide type and drug to polymer (D/P)
      ratio, were optimized for % release after 5 min (R%5 min) and time required for
      80% release (T80%). The suitability of the selected formulae for nasal
      application was evaluated by ex vivo mucoadhesion, in vitro cytocompatability and
      tolerability studies. A pharmacodynamic study in diabetic rats was conducted.
      Results showed that both polysaccharide type and amount greatly influenced the
      chosen responses. REP was highly incorporated in mucoadhesive MPs with proven
      safety on the rat nasal mucosa. The selected REP loaded powders exhibited a
      significant two to threefold increase in total decrease in blood glucose compared
      to the nasal and intravenous solutions.

PMID- 24751275
TI  - Unrefined wood hydrolysates are viable reactants for the reproducible synthesis
      of highly swellable hydrogels.
AB  - A value-adding robust and sequential synthetic pathway was elaborated to produce
      hydrogel structures with ionic character from crude acetylated galactoglucomannan
      rich wood hydrolysate (WH). The WH was first-step liquor originating from a
      sulphite cracking pulp process for dissolving pulp. The synthetically modified WH
      fractions were verified at each step by NMR and FTIR, and the hydrogels were
      characterized with respect to their swelling and mechanical properties. Altering
      the crosslinking chemistry and the content of ionic moieties resulted in
      hydrogels with various swelling ratios and mechanical properties. Renewable
      hydrogel formulations with swelling ratios as high as Qeq=270 were achieved. 

PMID- 24751274
TI  - Polybutylene succinate adipate/starch blends: a morphological study for the
      design of controlled release films.
AB  - Films made of plasticized starch (PLS)/poly(butylene succinate co-butylene
      adipate) (PBSA) blends were prepared by thermomechanical processing varying the
      PBSA proportions in blends to obtain biphasic materials with distinct
      morphologies. These morphologies were characterized by selective extraction of
      each phase, microscopic observations, and selective water/oxygen permeation
      properties. These experiments allowed identifying the blend compositions
      corresponding to the beginning of partial continuity (cluster partial
      percolation) until total continuity of each phases. This property was related to
      the controlled release of model molecule (fluorescein) previously dispersed in
      the PLS and revealed that its release depended on the tortuosity of the PLS phase
      tailored by the polymer blends composition and by the limited swelling of the PLS
      when entrapped in the PBSA phase. Future applications will focus on food
      preservatives dispersed in PBSA-PLS blends to obtain active antimicrobial
      packaging put in direct contact with intermediate to high moisture foods. 

PMID- 24751276
TI  - Green synthesis of colloid silver nanoparticles and resulting biodegradable
      starch/silver nanocomposites.
AB  - Environmentally friendly silver nanocomposite films were prepared by an ex situ
      method consisting firstly in the preparation of colloidal silver dispersions and
      secondly in the dispersion of the as-prepared nanoparticles in a potato
      starch/glycerol matrix, keeping a green chemistry process all along the synthesis
      steps. In the first step concerned with the preparation of the colloidal silver
      dispersions, water, glucose and soluble starch were used as solvent, reducing
      agent and stabilizing agent, respectively. The influences of the glucose amount
      and reaction time were investigated on the size and size distribution of the
      silver nanoparticles. Two distinct silver nanoparticle populations in size
      (diameter around 5 nm size for the first one and from 20 to 50 nm for the second
      one) were distinguished and still highlighted in the potato starch/glycerol based
      nanocomposite films. It was remarkable that lower nanoparticle mean sizes were
      evidenced by both TEM and UV-vis analyses in the nanocomposites in comparison to
      the respective colloidal silver dispersions. A dispersion mechanism based on the
      potential interactions developed between the nanoparticles and the polymer matrix
      and on the polymer chain lengths was proposed to explain this morphology. These
      nanocomposite film series can be viewed as a promising candidate for many
      applications in antimicrobial packaging, biomedicines and sensors.

PMID- 24751277
TI  - Structure-property relationships of reactively compatibilized PHB/EVA/starch
      blends.
AB  - A method is addressed to prepare poly(hydroxybutyrate)/poly(ethylene-co-vinyl
      acetate)/starch (PHB/EVA/starch) blends with fine dispersion of starch, i.e. by
      an in situ compatibilization in the presence of maleic anhydride (MA) and
      peroxide. The starch particle size is reduced from hundreds-MUm to sub-MUm after
      the compatibilization accompanied by an improvement in interfacial adhesion.
      Meanwhile, starch-in-EVA-type morphology is observed in the blends. The EVA and
      starch gradually changed into a (partially) co-continuous phase with increasing
      MA content. Consequently, toughness of the blends was improved as evidenced by an
      increase in elongation at break and tensile-fracture energy (work). Cavitation,
      fibrillation and matrix yielding are regarded as the toughening mechanism for the
      compatibilized blends. In addition, the Tg of the EVA phase is dependent on its
      phase morphology in the blends while the thermal behavior of the PHB was only
      slightly affected by the compatibilization.

PMID- 24751278
TI  - Thermoresponsive starch derivates with widely tuned LCSTs by introducing short
      oligo(ethylene glycol) spacers.
AB  - Water soluble, thermoresponsive 3-[2-butoxy(ethoxy)m]-2-hydroxypropyl starch
      ethers (BEmS) (m=0, 1, or 2) were prepared by reacting degraded waxy maize starch
      with n-butyl glycidyl ether, 3-(2-n-butoxyethyl) glycidyl ether, and 3-[2-(2-n
      butoxyethoxy)ethyl] glycidyl ether, respectively. The lower critical solution
      temperatures (LCSTs) of BEmS could be tuned to a wide range from 17.5 degrees C
      to 55.0 degrees C by changing the side chain lengths of oligo(ethylene glycol)
      groups and their average molar substitution (MS). The LCSTs of BEmS increase with
      increasing side chain length of oligo(ethylene glycol) groups when BS, BES, and
      BE2S have similar MS values. By contrast, an increase in BEmS concentration and
      addition of NaCl to the BEmS solutions could lead to a decrease in the LCSTs of
      BEmS. In addition, the effects of NaCl and BEmS concentrations on the LCSTs
      become weaker when the side chain length of oligo(ethylene glycol) groups
      increase.

PMID- 24751279
TI  - Preparation of the sodium salt of high acyl gellan and characterization of its
      structure, thermal and rheological behaviors.
AB  - This work presents a method to obtain the sodium salt of high acyl gellan (NaHAG)
      from a commercial preparation, LT-100, by ionic exchange and freeze drying
      without involving alcohol precipitation to recover the modified macromolecule.
      NaHAG was characterized by atomic absorption spectrophotometry, attenuated total
      reflectance Fourier transform infrared spectroscopy, X-ray diffraction and proton
      nuclear magnetic resonance. In addition, gel viscoelasticity, sol-gel transition
      temperatures from rheological temperature sweeps and differential scanning
      calorimetry, of both preparations was examined. Up to 87% of the initial weight
      of LT-100 was recovered as NaHAG. The sodium ion content in NaHAG was 3.2 times
      greater than in LT-100 and more than 90% of potassium, calcium and magnesium ions
      present in the original sample were removed. Transition temperatures of LT-100
      were significantly higher than those of NaHAG. However, LT-100 gels were slightly
      stronger and elastic than NaHAG gels. Characterization data from different
      analyses suggest that the treatment method makes possible to obtain NaHAG with
      only slight structure modification with respect to LT-100, and could be
      advantageously utilized to obtain other monovalent and divalent salt forms of
      high acyl gellan for use in fundamental studies on its properties in aqueous
      environment. 

PMID- 24751280
TI  - Crosslinker effects on functional properties of alginate/N-succinylchitosan based
      hydrogels.
AB  - In this paper, physico-chemical, mechanical and antimicrobial properties of
      hydrogels based on alginate/N-succinylchitosan blends crosslinked by calcium or
      zinc ions containing cellulose microfibers were investigated and discussed. With
      respect to plain alginate hydrogels, the addition of N-succinylchitosan
      significantly improved properties such as swelling degree and stability in saline
      solution. The water vapour transmission rate confirmed that all the hydrogels
      were able to assure a moist wound environment. Morphological analysis showed a
      good embedding of fibres within the zinc crosslinked hydrogels. In addition, zinc
      crosslinked hydrogels evidenced antimicrobial activity against two common skin
      pathogenic bacteria, Staphylococcus aureus and Escherichia coli. Cytotoxicity
      assays proved that the amount of zinc released is slightly over the toxic level.
      Overall, the characteristics of the zinc-crosslinked hydrogels showed their
      potential interest as materials for wound dressing.

PMID- 24751281
TI  - Production and purification of a fungal chitosanase and chitooligomers from
      Penicillium janthinellum D4 and discovery of the enzyme activators.
AB  - Chitosanases have received much attention because of their wide range of
      applications. Although most fungal chitosanases use sugar as their major carbon
      source, in the present work, a chitosanase was induced from a squid pen powder
      (SPP)-containing Penicillium janthinellum D4 medium and purified by ammonium
      sulphate precipitation and combined column chromatography. The purified D4
      chitosanase exhibited optimum activity at pH 7-9, 60 degrees C and was stable at
      pH 7-11, 25-50 degrees C. The D4 chitosanase that was used for chitooligomers
      preparation was studied. The enzyme products revealed various chitooligomers with
      different degrees of polymerisation (DP) from 3 to 9, as determined by a MALDI
      TOF mass spectrometer, confirming the endo-type nature of the D4 chitosanase. D4
      chitosanase activity was significantly inhibited by Cu(2+), Mn(2+), and EDTA.
      However, Fe(2+) activated or inhibited D4 chitosanases at different
      concentrations. The D4 chitosanase was also activated by some small synthetic
      boron-containing molecules with boronate ester side chains.

PMID- 24751282
TI  - Two-step enzymatic fingerprinting of sugar beet pectin.
AB  - A two-step enzymatic fingerprinting method was introduced to analyze a highly
      methylesterified and acetylated sugar beet pectin having a degree of
      methylesterification (DM) of 62 and acetylation of 30. A cocktail of pectolytic
      enzymes, including endo-polygalacturonase II (endo-PGII) and pectin lyase (PL),
      was used for the first digestion. The endo-PGII and PL resistant pectin fragments
      were isolated and subjected to a second digestion using fungal pectin
      methylesterase and endo-PGII. After the two sequential digestions, 78% of the
      total GalA residues present in the parental pectin were recovered as mono- and
      oligomers, which were used to quantitatively describe the parental SBP. For this
      reason, the descriptive parameters degree of blockiness (DBabs), degree of
      hydrolysis by PG (DHPG) and degree of hydrolysis by PL (DHPL) were established
      for both digestions. The first digestion revealed the presence of short blocks of
      nonesterified GalA residues and blocks of partly methylesterified and acetylated
      GalA residues in the parental SBP, in addition to blocks of highly
      methylesterified and acetylated GalA residues. The second digestion revealed the
      presence of blocks of methylesterified, partly methylesterified and/or acetylated
      GalA residues in a sequence not to be degradable by neither endo-PGII nor by PL.
      The acetyl groups were present in an blockwise manner. Application of the method
      to two differently prepared DM 50 SBPs showed that the two pectins differ in the
      ratio of blocks of nonesterified and blocks of partly methylesterified and
      acetylated GalA residues.

PMID- 24751284
TI  - Calcinosis cutis following seasonal influenza vaccination.

PMID- 24751283
TI  - The compensatory enrichment of sphingosine -1- phosphate harbored on glycated
      high-density lipoprotein restores endothelial protective function in type 2
      diabetes mellitus.
AB  - BACKGROUND: Glycation of high-density lipoprotein (HDL) decreases its ability to
      induce cyclooxygenase-2 (COX-2) expression and prostacyclin I-2 (PGI-2) release
      in endothelial cells. Whether lipid content of HDL, especially sphingosine-1
      phosphate (S1P), plays any specific role in restoring the protective function of
      HDL in type 2 diabetes mellitus (T2DM) is still unknown. METHODS AND RESULTS:
      Immunochemical techniques demonstrated that glycated HDL loses its protective
      function of regulating COX-2 expression compared with diabetic HDL. We proved
      that the lipid content, especially phospholipid content differed between diabetic
      HDL and glycated HDL. Levels of HDL-c-bound S1P were increased in T2DM compared
      with control subjects as detected by UPLC-MS/MS (HDL-c-bound S1P in control
      subjects vs. T2DM: 309.1 +/- 13.71 pmol/mg vs. 382.1 +/- 24.45 pmol/mg, P <
      0.05). Additionally, mRNA levels of S1P lyase enzymes and S1P phosphatase 1/2
      were decreased in peripheral blood by real-time PCR. Antagonist of S1P receptor 1
      and 3 (S1PR1/3) diminished the functional difference between apoHDL&PL (HDL
      containing the protein components and phospholipids) and diabetic apoHDL&PL
      (diabetic HDL containing the protein components and phospholipids). With
      different doses of S1P reconstituted on glycated HDL, its function in inducing
      the COX-2 expression was restored to the same level as diabetic HDL. The
      mechanism of S1P reconstituted HDL (rHDL) in the process of regulating COX-2
      expression involved the phosphorylation of ERK/MAPK-CREB signal pathway.
      CONCLUSION/SIGNIFICANCE: S1P harbored on HDL is the main factor which restores
      its protective function in endothelial cells in T2DM. S1P and its receptors are
      potential therapeutic targets in ameliorating the vascular dysfunction in T2DM.

PMID- 24751285
TI  - EXONSAMPLER: a computer program for genome-wide and candidate gene exon sampling
      for targeted next-generation sequencing.
AB  - The computer program EXONSAMPLER automates the sampling of thousands of exon
      sequences from publicly available reference genome sequences and gene annotation
      databases. It was designed to provide exon sequences for the efficient, next
      generation gene sequencing method called exon capture. The exon sequences can be
      sampled by a list of gene name abbreviations (e.g. IFNG, TLR1), or by sampling
      exons from genes spaced evenly across chromosomes. It provides a list of genomic
      coordinates (a bed file), as well as a set of sequences in fasta format. User
      adjustable parameters for collecting exon sequences include a minimum and maximum
      acceptable exon length, maximum number of exonic base pairs (bp) to sample per
      gene, and maximum total bp for the entire collection. It allows for partial
      sampling of very large exons. It can preferentially sample upstream (5 prime)
      exons, downstream (3 prime) exons, both external exons, or all internal exons. It
      is written in the Python programming language using its free libraries. We
      describe the use of EXONSAMPLER to collect exon sequences from the domestic cow
      (Bos taurus) genome for the design of an exon-capture microarray to sequence
      exons from related species, including the zebu cow and wild bison. We collected
      ~10% of the exome (~3 million bp), including 155 candidate genes, and ~16,000
      exons evenly spaced genomewide. We prioritized the collection of 5 prime exons to
      facilitate discovery and genotyping of SNPs near upstream gene regulatory DNA
      sequences, which control gene expression and are often under natural selection.

PMID- 24751286
TI  - Continuous endotracheal tube cuff pressure control system protects against
      ventilator-associated pneumonia.
AB  - INTRODUCTION: The use of a system for continuous control of endotracheal tube
      cuff pressure reduced the incidence of ventilator-associated pneumonia (VAP) in
      one randomized controlled trial (RCT) with 112 patients but not in another RCT
      with 142 patients. In several guidelines on the prevention of VAP, the use of a
      system for continuous or intermittent control of endotracheal cuff pressure is
      not reviewed. The objective of this study was to compare the incidence of VAP in
      a large sample of patients (n = 284) treated with either continuous or
      intermittent control of endotracheal tube cuff pressure. METHODS: We performed a
      prospective observational study of patients undergoing mechanical ventilation
      during more than 48 hours in an intensive care unit (ICU) using either continuous
      or intermittent endotracheal tube cuff pressure control. Multivariate logistic
      regression analysis (MLRA) and Cox proportional hazard regression analysis were
      used to predict VAP. The magnitude of the effect was expressed as odds ratio (OR)
      or hazard ratio (HR), respectively, and 95% confidence interval (CI). RESULTS: We
      found a lower incidence of VAP with the continuous (n = 150) than with the
      intermittent (n = 134) pressure control system (22.0% versus 11.2%; p = 0.02).
      MLRA showed that the continuous pressure control system (OR = 0.45; 95% CI = 0.22
      0.89; p = 0.02) and the use of an endotracheal tube incorporating a lumen for
      subglottic secretion drainage (SSD) (OR = 0.39; 95% CI = 0.19-0.84; p = 0.02)
      were protective factors against VAP. Cox regression analysis showed that the
      continuous pressure control system (HR = 0.45; 95% CI = 0.24-0.84; p = 0.01) and
      the use of an endotracheal tube incorporating a lumen for SSD (HR = 0.29; 95% CI
      = 0.15-0.56; p < 0.001) were protective factors against VAP. However, the
      interaction between type of endotracheal cuff pressure control system (continuous
      or intermittent) and endotracheal tube (with or without SSD) was not
      statistically significant in MLRA (OR = 0.41; 95% CI = 0.07-2.37; p = 0.32) or in
      Cox analysis (HR = 0.35; 95% CI = 0.06-1.84; p = 0.21). CONCLUSIONS: The use of a
      continuous endotracheal cuff pressure control system and/or an endotracheal tube
      with a lumen for SSD could help to prevent VAP in patients requiring more than 48
      hours of mechanical ventilation.

PMID- 24751287
TI  - Rickettsia spp. in seabird ticks from western Indian Ocean islands, 2011-2012.
AB  - We found a diversity of Rickettsia spp. in seabird ticks from 6 tropical islands.
      The bacteria showed strong host specificity and sequence similarity with strains
      in other regions. Seabird ticks may be key reservoirs for pathogenic Rickettsia
      spp., and bird hosts may have a role in dispersing ticks and tick-associated
      infectious agents over large distances. 

PMID- 24751288
TI  - Why are some microbes more ubiquitous than others? Predicting the habitat breadth
      of soil bacteria.
AB  - Identifying the traits that determine spatial distributions can be challenging
      when studying organisms, like bacteria, for which phenotypic information is
      limited or non-existent. However, genomic data provide another means to infer
      traits and determine the ecological attributes that account for differences in
      distributions. We determined the spatial distributions of ~124 000 soil bacterial
      taxa across a 3.41 km(2) area to determine whether we could use phylogeny and/or
      genomic traits to explain differences in habitat breadth. We found that occupancy
      was strongly correlated with environmental range; taxa that were more ubiquitous
      were found across a broader range of soil conditions. Across the ~500 taxa for
      which genomic information was available, genomic traits were more useful than
      phylogeny alone in explaining the variation in habitat breadth; bacteria with
      larger genomes and more metabolic versatility were more likely to have larger
      environmental and geographical distributions. Just as trait-based approaches have
      proven to be so useful for understanding the distributions of animals and plants,
      we demonstrate that we can use genomic information to infer microbial traits that
      are difficult to measure directly and build trait-based predictions of the
      biogeographical patterns exhibited by microbes.

PMID- 24751290
TI  - Metal free synthesis of homoallylic alcohols promoted by ultrasound.
AB  - The use of ultrasound irradiation to promote the allylation of aldehydes
      containing different functionalities with potassium allyltrifluoroborates is
      described. The method features the use of a minimum amount of acetone as solvent,
      without any other catalyst or promoter. The products were obtained in high
      yields, short reaction times, at room temperature and without the need of further
      purification. 

PMID- 24751289
TI  - Optimal linear combination of ARFI, transient elastography and APRI for the
      assessment of fibrosis in chronic hepatitis B.
AB  - BACKGROUND & AIMS: Accurate assessment of liver fibrosis in patients with chronic
      hepatitis B (CHB) is necessary not only to predict the long-term clinical course
      but also to determine an appropriate antiviral therapy scheme. Several
      noninvasive approaches - serum markers and elastography - have been proposed as
      alternatives for the histopathological analysis of liver biopsies. The aim of
      this study was to evaluate two ultrasound elastography methods (ARFI and TE) and
      one biochemical test (APRI), as well as their optimal linear combination, in the
      assessment of liver fibrosis in CHB. METHODS: Ninety five patients with CHB and
      16 volunteers underwent ARFI, TE and APRI; and liver fibrosis was staged in the
      patients by a liver biopsy. An optimal linear combination of the three methods
      was developed, and its diagnostic performance was evaluated by a 10-fold cross
      validation. RESULTS: The accuracy of the linear combination was 83.86% and 91.88%
      for significant fibrosis (>=F2) and cirrhosis (F4), respectively, higher than
      those obtained for ARFI (83.50%, 88.76%), TE (75.27%, 87.61%) and APRI (73.29%
      and 81.67%). The combination also increased the sensitivity and the negative
      predictive values for the diagnosis of significant fibrosis and cirrhosis.
      CONCLUSIONS: The optimal linear combination algorithm is effective for
      noninvasive staging of liver fibrosis in CHB. However, linear combination has its
      own limitations; nonlinear methods may eventually reveal even clearer diagnostic
      results.

PMID- 24751291
TI  - Enhancing decomposition rate of perfluorooctanoic acid by carbonate radical
      assisted sonochemical treatment.
AB  - Perfluorooctanoic acid (PFOA) is a recalcitrant organic pollutant in wastewater
      because of its wide range of applications. Technologies for PFOA treatment have
      recently been developed. In this study, PFOA decomposition by sonochemical
      treatment was investigated to determine the effects of NaHCO3 concentrations, N2
      saturation, and pH on decomposition rates and defluorination efficiencies. The
      results showed that PFOA decomposition by ultrasound treatment only (150 W, 40
      kHz), with or without saturated N2, was <25% after 4 h reaction. The extent and
      rate of PFOA decomposition and defluorination efficiencies of PFOA, however,
      greatly increased with the addition of carbonate radical reagents. PFOA was
      completely decomposed after 4h of sonochemical treatment with a carbonate radical
      oxidant and saturated N2. Without saturated N2, PFOA was also decomposed to a
      high (98.81%) degree. The highest PFOA decomposition and defluorination
      efficiencies occurred in N2 saturated solution containing an initial NaHCO3
      concentration of 30 mM. Sonodecomposition of PFOA with CO3(-) radical was most
      favorable in a slightly alkaline environment (pH=8.65). There isn't any shorter
      chain perfluorinated carboxylic acids detected except fluorine ions in final
      reaction solution.

PMID- 24751292
TI  - Ultrasound improves the renneting properties of milk.
AB  - The effects of ultrasound application on skim milk (10% w/w total solids at
      natural pH 6.7 or alkali-adjusted to pH 8.0) prior to the renneting of milk at pH
      6.7 were examined. Skim milk, made by reconstituting skim milk powder, was
      sonicated at 20kHz and 30 degrees C (dissipated power density 286kJkg(-1)) in an
      ultrasonic reactor. The rennet gelation time, curd firming rate, curd firmness,
      and the connectivity of the rennet gel network were improved significantly in
      rennet gels made from milk ultrasonicated at pH 8.0 and re-adjusted back to pH
      6.7 compared to those made from milk sonicated at pH 6.7. These renneting
      properties were also improved in milk sonicated at pH 6.7 compared to those of
      the non-sonicated control milk. The improvements in renneting behavior were
      related to ultrasound-induced changes to the proteins in the milk. This study
      showed that ultrasonication has potential to be used as an intervention to
      manipulate the renneting properties of milk for more efficient manufacturing of
      cheese. 

PMID- 24751293
TI  - Old and new approaches to DNA breathing: Comments on "Fluctuations in the DNA
      double helix: A critical review" by M.D. Frank-Kamenetskii and S. Prakash.

PMID- 24751294
TI  - Expression of alpha-gustducin and alpha-transducin, G proteins coupled with taste
      receptors, in boar sperm.
AB  - During the transit in the female genital tract, spermatozoa are exposed to an
      environment that varies in composition from the vagina to the oviduct. Because G
      proteins, alpha-gustducin and alpha-transducin, are accepted as markers of
      chemosensitive cells, this study was aimed at assessing whether these proteins
      are expressed in boar germ cells. Ejaculated sperm extracts were analyzed by
      Western blot, and indirect immunofluorescence was performed on testis sections,
      smears of epididymal and ejaculated spermatozoa, sperm cells after in vitro
      induction of capacitation and acrosome reaction (IVAR), and in sperm cells bound
      to zona pellucida during IVF. Based on immunoblot results, both G proteins are
      present in boar sperm. In the testicular tissue sections, alpha-gustducin and
      alpha-transducin positivity was recorded in the germinal cells near the tubular
      lumen, whereas no positive signal was evident in spermatogonia located in the
      outer region of the seminiferous tubules. alpha-Gustducin expression in
      epididymal and ejaculated spermatozoa was mainly detectable in both the acrosome
      and the principal piece of the tail, whereas alpha-transducin was confined to the
      acrosome and the midpiece. No changes after in vitro induction of capacitation
      and IVAR were observed, except for the disappearance of acrosomal positivity in
      reacted spermatozoa. In sperm bound to zona pellucida, the G protein signal was
      congruent with that observed in IVAR cells. To the best of our knowledge, this is
      the first description of alpha-transducin in mammalian sperm and the first
      description of alpha-gustducin in boar sperm. Further studies are needed to
      clarify the possible role of these G proteins in sperm physiology. 

PMID- 24751295
TI  - Myasthenia gravis associated with acute hepatitis E infection in immunocompetent
      woman.

PMID- 24751296
TI  - Neonatal perforated Amyand's hernia presenting as an enterocutaneous scrotal
      fistula.
AB  - Perforation of the vermiform appendix in a septic neonate with an Amyand's hernia
      resulted in the formation of a scrotal enterocutaneous fistula. In conclusion
      from this exceptional complication, active parental awareness for any neonatal
      scrotal swelling is required, and an early operative policy for the neonatal
      inguinal hernia is significant. 

PMID- 24751298
TI  - Measuring HINARI use in Nigeria through a citation analysis of Nigerian Journal
      of Clinical Practice.
AB  - BACKGROUND: HINARI is one of the four programmes of Research4Life managed by the
      World Health Organization in partnership with Yale University Library. HINARI
      provides online access to the world's health-related scientific literature free
      or at very low cost to researchers in developing countries. The research examined
      the use of HINARI through a 5-year (2007-2011) citation analysis of Nigerian
      Journal of Clinical Practice. METHOD: The study was a citation analysis of 5
      years of published volumes of Nigerian Journal of Clinical Practice. The analysis
      was carried out using issues ranging from volume 10 (2007) to 14 (2011). The use
      of HINARI was determined by comparing the total journal titles and articles cited
      from HINARI with non-HINARI journals in the five volumes of Nigerian Journal of
      Clinical Practice (NJCP). RESULTS: Results show that only 42.8% of the journal
      titles cited are available in HINARI. On the contrary, in terms of total articles
      cited from the journals, HINARI had a higher citation of 56.1% with a greater
      citation frequency of individual titles. CONCLUSION: The higher article citations
      and repeated use of individual titles available in HINARI suggest that health
      researchers in Nigeria are using the HINARI resource to a measurable extent.

PMID- 24751297
TI  - Estrogen degradation and sorption onto colloids in a constructed wetland with
      different hydraulic retention times.
AB  - Endocrine disrupting compounds are a global concern, owing to their interference
      with the endocrine system of wildlife. In particular, natural estrogens at
      concentrations as low as ng/L level can interrupt the endocrine system of many
      organisms. A constructed wetland is an effective means of removing the residual
      levels of estrogen. This study investigates the estrogen degradation and sorption
      on colloids in a constructed wetland at hydraulic retention times (HRTs) of 27.5,
      45.9, and 137.5h. Three natural estrogens (i.e. estrone (E1), 17beta-estradiol
      (E2), and estriol (E3)) are analyzed with liquid chromatography/tandem mass
      spectrometry. At HRT=27.5h, no degradation occurs; at HRT=45.9h, the degradation
      rates are 0-46.2%; and at HRT=137.5h, the degradation rates are 40-84.3%.
      Additionally, estrogen sorption coefficients (logKCOC values) range from 3.37 to
      4.89. Average logKCOC values are 4.08+/-0.33, 4.04+/-0.34, and 4.11+/-0.28 for
      E1, E2, and E3, respectively. At different HRTs, values of logKCOC increase with
      an increasing HRT. Analytical results indicate that constructed wetlands can
      remove residual natural estrogens. With an increasing HRT, the estrogen
      degradation rate increases as well as the estrogen sorption on colloids. 

PMID- 24751299
TI  - The effects of mental state on assessment of bipolar temperament.
AB  - BACKGROUND: Although the Temperament Evaluation of Memphis, Pisa, Paris and San
      Diego-auto questionnaire (TEMPS-A) was designed to identify temperaments which
      derive from traits but not states, there is a possibility that TEMPS-A scores
      might be affected by mental state in non-clinical populations. For the purpose of
      clarifying the effects of mental state on TEMPS-A scores, it is worthwhile to
      examine associations of the full version of the TEMPS-A with various depressive
      scales and, if possible, mania rating scales. METHODS: TEMPS-A data acquired from
      314 medical students and staff was used to investigate the association of
      temperament scores with mental assessment scores such as the Beck Depression
      Inventory (BDI), the Quick Inventory of Depressive Symptomatology Self-Report
      Japanese version (QIDS-SR-J), the Patient Health Questionnaire-9 (PHQ-9), the
      Hamilton Depression rating scale (HAM-D) and the Young Mania Rating Scale (YMRS).
      RESULTS: Depressive state scores were significantly and positively associated
      with depressive, anxious, cyclothymic, and irritable temperament scores of TEMPS
      A whereas sub-threshold hypomanic state scores were significantly and positively
      associated with irritable temperament of TEMPS-A. There was no association
      between depressive state or sub-threshold hypomanic state and hyperthymic
      temperament scores. LIMITATIONS: The nature of the present study is cross
      sectional, and it is unknown whether depressive and/or sub-threshold hypomanic
      states may have affected temperament scores or whether temperament scores might
      have affected depressive and/or sub-threshold hypomanic scores. Other limitations
      are that the sample may not represent the entire population and that there is no
      evidence that Japanese findings can be applicable outside Japan. CONCLUSIONS: It
      is worthwhile to consider the effects of mental state on temperament scores of
      TEMPS-A even in non-clinical population.

PMID- 24751300
TI  - Low baseline salivary 3-methoxy-4-hydroxyphenylglycol (MHPG) in drug-naive
      patients with short-illness-duration first episode major depressive disorder.
AB  - BACKGROUND: Central noradrenergic dysfunction with autonomic nervous system
      dysregulation are reported in major depressive disorder (MDD). Salivary 3-methoxy
      4-hydroxyphenylglycol (sMHPG) is indicative of central noradrenergic activity.
      Studies on MHPG in bodily fluids are inconsistent and scarce data is available
      regarding baseline sMHPG concentration in MDD. METHODS: The basal, non-stimulated
      sMHPG concentration was studied in this cross-sectional case-control study on 20
      non-late-life adult, short-illness-duration first-episode, treatment-naive MDD
      patients and in 20 age- and sex-matched healthy controls. Depressed patients
      showed a score in the Hamilton rating scale for depression (HAMD-17) higher than
      20. RESULTS: The baseline sMHPG concentration was significantly lower in
      depressed individuals as compared to controls (p=0.025). In post hoc analysis
      significantly lower sMHPG was present in melancholic MDD (p=0.009) as related to
      controls whereas no difference was seen between non-melancholic MDD patients and
      controls. The concentration of sMHPG was not significantly correlated neither
      with duration nor the severity of depressive symptoms as measured by the total
      HAMD-17 score. LIMITATIONS: The current study is limited by its cross-sectional
      design and small sample size. CONCLUSION: Low baseline sMHPG concentration was
      found in MDD. The study provides no support for elevated sMHPG in drug-naive
      patients with short-illness-duration first episode MDD. Taken into account the
      physiology of sMHPG secretion the study results corroborate with the evidence for
      decreased central noradrenergic activity in MDD when sMHPG is considered
      indicative of central noradrenergic function.

PMID- 24751301
TI  - Beyond a single index of mania symptoms: structure and validity of subdimensions.
AB  - BACKGROUND: DSM-5 portrays mania as unitary despite evidence of distinct symptom
      clusters. Studies investigating the structure of mania have been inconsistent, in
      part because many relied on instruments not designed for this question. The
      present work used a clinical interview designed for structural analysis in order
      to identify and validate subdimensions specific to mania symptoms. METHODS:
      Psychiatric outpatients (N=422) and undergraduates with a history of mental
      health treatment (N=306) were interviewed with a comprehensive measure of mood
      and anxiety that included 24 manic symptoms. Patients completed additional
      measures of symptoms and functioning, and a semi-structured diagnostic interview.
      RESULTS: A 4-factor model of mania replicated across independent samples and was
      superior in fit to competing models, including the unidimensional model implied
      whenever researchers or clinicians use only a total score for mania. The factors
      were only moderately correlated, and three of the four ("Irritability" was the
      exception) showed a strong criterion, convergent and discriminant validity,
      suggesting they are specific to mania. Subdimensions showed distinct and
      meaningful associations with functioning. LIMITATIONS: Symptoms of psychosis and
      depression are important features of manic episodes, but were not included in the
      present study since they lack specificity to mania. CONCLUSIONS: Mania is
      multifaceted. At least three subdimensions specific to mania were identified
      ("Euphoric Activation," "Hyperactive Cognition" and "Reckless Overconfidence").
      Use of subdimensions, in addition to overall mania severity, may enhance the
      ability of studies to detect meaningful biological correlates of bipolar
      disorder. Moreover, their different associations with functioning suggest
      assessing subdimensions has clinical utility as well.

PMID- 24751302
TI  - Effect of dysfunctional attitudes and postpartum state on vulnerability to
      depressed mood.
AB  - BACKGROUND: Postpartum depression (PPD) is the most common complication of
      childbearing with a 13% prevalence. Vulnerability to depressed mood has an
      important role in the onset of major depressive episodes (MDE), but has not been
      investigated in postpartum. The aim is to assess whether day-5 postpartum blues
      and severity of dysfunctional attitudes predicts vulnerability to depressed mood.
      METHODS: About 45 healthy women were recruited: group 1 (n=12) was day-5
      postpartum during the typical peak of postpartum blues. Group 2 (n=11) was within
      18 months postpartum and reported a vulnerability to cry (and had elevated
      dysfunctional attitudes but no MDE). Group 3 (n=11) was within 18 months
      postpartum and no vulnerability to cry. Group 4 (n=11) was not recently
      postpartum. Vulnerability to depressed mood was measured by the change in the
      visual analog scale from the sad mood induction procedure (MIP). RESULTS:
      Univariate analysis of covariance demonstrated that day-5 postpartum blues and
      level of dysfunctional attitudes were highly predictive of change in sad mood
      (postpartum blues: F(1,41)=12.9, p<0.005, dysfunctional attitudes scale score:
      F(1,41)=11.49, p<0.005). LIMITATIONS: Although the effects were robust, sample
      sizes were 11-12 within each group. CONCLUSION: Two factors (day-5 postpartum and
      severity of dysfunctional attitudes) predicted vulnerability to sad mood. Since
      the severity of postpartum blues predicts PPD, MIP on day-5 postpartum represents
      a quantitative measure that can be applied to screen novel, early interventions
      for preventing PPD. Interventions to prevent PPD through increasing resilience
      against mood induction should target postpartum women with greater severity of
      dysfunctional attitudes.

PMID- 24751303
TI  - Why are anxiety and depressive symptoms comorbid in youth? A multi-wave,
      longitudinal examination of competing etiological models.
AB  - BACKGROUND: The present study sought to clarify the development of comorbid
      emotional distress by comparing different explanations for how youth develop
      anxiety and depressive symptoms. Specifically, we introduced the diathesis
      anxiety approach (whether cognitive vulnerabilities interact with anxiety
      symptoms), and compared it to a causal model (anxiety symptoms predicting
      depressive symptoms), and a correlated liabilities model (whether cognitive
      vulnerabilities interacted with stressors to predict both anxiety and depressive
      symptoms) to examine which model best explained the relation between depressive
      and anxiety symptoms in youth. METHODS: 678 3rd (n=208), 6th (n=245), and 9th
      (n=225) grade girls (n=380) and boys (n=298) completed self-report measures at
      baseline assessing cognitive vulnerabilities (rumination and self-criticism),
      stressors, depressive and anxiety symptoms. Every 3 months over the next 18
      months, youth completed follow-up measures of symptoms and stressors. RESULTS:
      While limited support was found for a causal (p>0.10) or correlated-liability
      model (p>0.05) for comorbidity, findings did support a diathesis-anxiety approach
      for both self-criticism (t(2494)=3.36, p<0.001) and rumination (t(2505)=2.40,
      p<0.05). LIMITATIONS: The present study's findings are based on self-report
      measure and makes inferences concerning comorbidity with a community sample.
      CONCLUSIONS: These results may help clarify past research concerning comorbidity
      by introducing a diathesis-anxiety approach as a viable model to understand which
      youth are most at-risk for developing comorbid emotional distress.

PMID- 24751305
TI  - The Repeated Episodes of Self-Harm (RESH) score: A tool for predicting risk of
      future episodes of self-harm by hospital patients.
AB  - BACKGROUND: Repetition of hospital-treated deliberate self-harm is common.
      Several recent studies have used emergency department data to develop clinical
      tools to assess risk of self-harm or suicide. Longitudinal, linked inpatient data
      is an alternative source of information. METHODS: We identified all individuals
      admitted to hospital for deliberate self-harm in two Australian states (~350
      hospitals). The outcome of interest was a repeated episode of self-harm (non
      fatal or fatal) within 6 months. Logistic regression was used to identify a set
      of predictors of repetition. A risk calculator (RESH: Repeated Episodes of Self
      Harm) was derived directly from model coefficients. RESULTS: There were 84,659
      episodes of self-harm during the study period. Four variables - number of prior
      episodes, time between episodes, prior psychiatric diagnoses and recent
      psychiatric hospital stay - strongly predicted repetition. The RESH score showed
      good discrimination (AUC=0.75) and had high specificity. Patients with scores of
      0-3 had 14% risk of repeat episodes, whereas patients with scores of 20-25 had
      over 80% risk. We identified five thresholds where the RESH score could be used
      for prioritising interventions. LIMITATIONS: The trade-off of a highly specific
      test is that the instrument has poor sensitivity. As a consequence, the RESH
      score cannot be used reliably for "ruling out" those who score below the
      thresholds. CONCLUSIONS: The RESH score could be useful for prioritising patients
      to interventions to reduce readmission for deliberate self-harm. The five
      thresholds, representing the continuum from low to high risk, enable a stepped
      care model of overlapping or sequential interventions to be deployed to patients
      at risk of self-harm.

PMID- 24751304
TI  - Effect of adjunctive benzodiazepines on clinical outcomes in lithium- or
      quetiapine-treated outpatients with bipolar I or II disorder: results from the
      Bipolar CHOICE trial.
AB  - BACKGROUND: Little is known about the longer-term effects of adjunctive
      benzodiazepines on symptom response during treatment in patients with bipolar
      disorders. METHODS: The study sample consisted of 482 patients with bipolar I or
      II disorder enrolled in a 6-month, randomized, multi-site comparison of lithium-
      and quetiapine-based treatment. Changes in clinical measures (BISS total and
      subscales, CGI-BP, and CGI-Efficacy Index) were compared between participants who
      did and did not receive benzodiazepine treatment at baseline or during follow-up.
      Selected outcomes were also compared between patients who did and did not
      initiate benzodiazepines during follow-up using stabilized inverse probability
      weighted analyses. RESULTS: Significant improvement in all outcome measures
      occurred within each benzodiazepine exposure group. Benzodiazepine users (at
      baseline or during follow-up) experienced significantly less improvement in BISS
      total, BISS irritability, and CGI-BP scores than did benzodiazepine non-users.
      There were no significant differences in these measures between patients who did
      and did not initiate benzodiazepines during follow-up in the weighted analyses.
      There was no significant effect of benzodiazepine use on any outcome measure in
      patients with comorbid anxiety or substance use disorders. LIMITATIONS: This is a
      secondary analysis of data from a randomized effectiveness trial that was not
      designed to address differential treatment response according to benzodiazepine
      use. CONCLUSIONS: Adjunctive benzodiazepines may not significantly affect
      clinical outcome in lithium- or quetiapine-treated patients with bipolar I or II
      disorder over 6 months, after controlling for potential confounding factors.

PMID- 24751306
TI  - Association of premenstrual/menstrual symptoms with perinatal depression and a
      polymorphic repeat in the polyglutamine tract of the retinoic acid induced 1
      gene.
AB  - BACKGROUND: Depression during pregnancy or after childbirth is the most frequent
      perinatal illness affecting women. We investigated the length distribution of a
      trinucleotide repeat in RAI1, which has not been studied in perinatal depression
      or in the Chinese population. METHODS: Cases (n=139) with confirmed diagnosis of
      clinical (major) depression related to pregnancy/postpartum were recruited from
      the outpatient clinic. Controls were patients who came to the obstetrics clinics
      and scored <7 on the Edinburgh Postnatal Depression Scale (EPDS) (n=540). Saliva
      samples for DNA analysis, demographic information and self-reported frequency of
      occurrence of various premenstrual/menstrual symptoms were collected from all
      participants. Genomic DNA was extracted from saliva and relevant region sequenced
      to determine the number of CAG/CAA repeats that encodes the polyglutamine tract
      in the N terminal of the protein. Difference between groups was assessed by chi
      square analysis for categorical variables and analysis of variance for
      quantitative scores. RESULTS: Compared to control subjects, patients with
      perinatal depression reported more frequent mood changes, cramps, nausea,
      vomiting, diarrhoea, and headache during premenstrual/menstrual periods
      (p=0.000). For the RAI1 gene CAG/CAA repeat, there was a statistically
      significant difference in the genotypic distribution between cases and controls
      (p=0.031). There was also a statistically significant association between the 14
      repeat allele and perinatal depression (p=0.016). LIMITATIONS: Family history,
      previous mental illness, and physical and psychological symptoms during the
      premenstrual/menstrual periods were self-reported. EPDS screening was done only
      once for controls. CONCLUSIONS: The RAI1 gene polyglutamine repeat has a
      different distribution in our population. The 14-repeat allele is associated with
      perinatal depression and more frequent experience of physical and psychological
      symptoms during menstrual period.

PMID- 24751308
TI  - Stressful life events in bipolar I and II disorder: cause or consequence of mood
      symptoms?
AB  - BACKGROUND: Life events are assumed to be triggers for new mood episodes in
      bipolar disorder (BD). However whether life events may also be a result of
      previous mood episodes is rather unclear. METHOD: 173 bipolar outpatients (BD I
      and II) were assessed every three months for two years. Life events were assessed
      by Paykel's self-report questionnaire. Both monthly functional impairment due to
      manic or depressive symptomatology and mood symptoms were assessed. RESULTS:
      Negative life events were significantly associated with both subsequent severity
      of mania and depressive symptoms and functional impairment, whereas positive life
      events only preceded functional impairment due to manic symptoms and mania
      severity. These associations were significantly stronger in BD I patients
      compared to BD II patients. For the opposite temporal direction (life events as a
      result of mood/functional impairment), we found that mania symptoms preceded the
      occurrence of positive life events and depressive symptoms preceded negative life
      events. LIMITATIONS: The use of a self-report questionnaire for the assessment of
      life events makes it difficult to determine whether life events are cause or
      consequence of mood symptoms. Second, the results can only be generalized to
      relatively stable bipolar outpatients, as the number of severely depressed as
      well as severely manic patients was low. CONCLUSIONS: Life events appear to
      precede the occurrence of mood symptoms and functional impairment, and this
      association is stronger in BD I patients. Mood symptoms also precede the
      occurrence of life event, but no differences were found between BD I and II
      patients.

PMID- 24751307
TI  - Is excess mortality higher in depressed men than in depressed women? A meta
      analytic comparison.
AB  - BACKGROUND: It is not well-established whether excess mortality associated with
      depression is higher in men than in women. METHODS: We conducted a meta-analysis
      of prospective studies in which depression was measured at baseline, where
      mortality rates were reported at follow-up, and in which separate mortality rates
      for men and women were reported. We conducted systematic searches in
      bibliographical databases and calculated relative risks of excess mortality in
      men and women. RESULTS: Thirteen studies were included. Among the people with
      depression, excess mortality in men was higher than in women (RR=1.97; 1.63
      2.37). Compared with non-depressed participants, excess mortality was increased
      in depressed women (RR=1.55; 95% CI: 1.32-1.82), but not as much as in men
      (RR=2.04; 95% CI: 1.76-2.37), and the difference between excess mortality in men
      was significantly higher than in women (p<0.05). CONCLUSIONS: Excess mortality
      related to depression is higher in men than in women. Although the exact
      mechanisms for this difference are not clear, it may point at differential or
      more intensified pathways leading from depression to increased mortality in
      depressed men compared to women.

PMID- 24751309
TI  - Physical (in)activity and depression in older people.
AB  - BACKGROUND: Knowledge about characteristics explaining low level of physical
      activity in late-life depression is needed to develop specific interventions
      aimed at improving physical health in depressed people above the age of 60.
      METHODS: This cross-sectional study used data from the Netherlands Study of
      Depression in Older Persons (NESDO), a longitudinal multi-site naturalistic
      cohort study. People aged 60 and over with current depression and a non-depressed
      comparison group were included, and total amount of PA per week was assessed with
      the short version of the International Physical Activity Questionnaire (IPAQ).
      Depression characteristics, socio-demographics, cognitive function, somatic
      condition, psycho-social, environment and other lifestyle factors were added in a
      multiple regression analysis. RESULTS: Depressed persons >60y were less
      physically active in comparison with non-depressed subjects. The difference was
      determined by somatic condition (especially, functional limitations) and by
      psychosocial characteristics (especially sense of mastery). Within the depressed
      subgroup only, a lower degree of physical activity was associated with more
      functional limitations, being an inpatient, and the use of more medication, but
      not with the severity of the depression. LIMITATION: This study is based on cross
      sectional data, so no conclusions can be drawn regarding causality. CONCLUSIONS:
      This study confirms that depression in people over 60 is associated with lower
      physical activity. Patient characteristics seem more important than the
      depression diagnosis itself or the severity of depression. Interventions aimed at
      improving physical activity in depressed persons aged 60 and over should take
      these characteristics into account.

PMID- 24751311
TI  - Polysomnographic sleep characteristics of generally-anxious and healthy children
      assessed in the home environment.
AB  - BACKGROUND: Using laboratory-based polysomnography (PSG) we recently provided
      evidence of significantly prolonged sleep onset latency (SOL) and reduced latency
      to rapid eye movement (REM) sleep among non-depressed children with generalized
      anxiety disorder (GAD) compared to healthy age-matched controls. In the current
      study we conducted unattended ambulatory PSG in a new sample of children with GAD
      and controls in order to examine sleeping characteristics in the home
      environment. METHOD: Thirty-two children (ages of 7-11 years) including 16
      children with primary GAD and 16 controls receiving no psychotropic medications
      were studied. The anxious group had a primary diagnosis of GAD without secondary
      mood disorders and controls were free of any medical or psychiatric diagnoses.
      All participants underwent structured diagnostic assessments and completed one
      night of home-based polysomnography (PSG). RESULTS: Children with GAD exhibited
      significantly higher sleep efficiency (SE) and fewer rapid eye movement (REM)
      sleep periods compared to controls. Self-reported somatic arousal during the pre
      sleep period was negatively correlated with the percentage of total REM sleep
      among controls, but positively correlated with REM sleep percentage in the GAD
      group. LIMITATIONS: A small sample size and one night of PSG only. CONCLUSIONS:
      Home-based PSG recording do not provide evidence of disrupted sleep patterns in
      children with GAD. Contextual factors that better elucidate differences between
      laboratory and home-based sleep findings are suggested as important directions
      for future research.

PMID- 24751310
TI  - Association analysis of COMT/MTHFR polymorphisms and major depressive disorder in
      Chinese Han population.
AB  - BACKGROUND: In several previous biochemical and genetic studies, the Val158Met
      polymorphism of the gene encoding catechol-O-methyltransferase (COMT) and the
      C677T polymorphism of Methylenetetrahydrofolate reductase (MTHFR) have been
      suggested to be involved in the pathogenesis as well as the treatment response of
      major depressive disorder (MDD), but the results have been inconsistent. In this
      study, we investigate the association of COMT/MTHFR and their interactions with
      MDD and antidepressant response in Chinese Han population. METHODS: Three hundred
      and sixty eight depressed patients who met DSM-IV criteria for MDD were recruited
      for the study. Two hundred and nineteen normal controls were recruited from the
      local community. Patients and normal controls were genotyped for the functional
      COMT val158met and MTHFR C677T polymorphisms. Patients were characterized for
      clinical response to antidepressant treatment as measured by intra-individual
      changes of Hamilton Depression (HAMD-17) scores over 6 weeks. RESULTS: The T
      allele (OR=1.81; CI95%=1.40-2.34, P<0.001) and C/T genotype (OR=3.66; CI95% =2.53
      5.28, P<0.001) of MTHFR C677T were significantly different between case and
      control groups. The COMT Met/Val genotype was more common among depressed
      individuals than among controls (OR=1.52, CI95%=1.04-2.21, P=0.02). LIMITATION:
      There is disequilibrium in age and sex between case and control groups. Though we
      control the two variables in the statistic analysis, to be more accurate, we need
      to increase sample size in further study. CONCLUSION: Individuals with the
      genotype COMT Met/Val and MTHFR C/T have more probability of suffering from MDD.
      However, there is no association between gene polymorphism and treatment
      response.

PMID- 24751312
TI  - An investigation into the relationship between first-degree relatives of bipolar
      affective disorder and (idiopathic) epilepsy in a sub-Saharan African population.
AB  - OBJECTIVE: Phenomenological, neuro-biological and pharmacological investigations
      linked bipolar affective disorders with epilepsy. Similarly, a large community
      based epidemiological study of epileptic patients reported that 12% of the
      participants had bipolar symptoms, a rate 7* higher than in control. Bipolar and
      epileptic disorders are epiphenomena of an underlying genetic susceptibility.
      This study aimed to determine the relationship between first-degree relatives of
      bipolar and epileptic patients in a sub-Saharan African population. METHOD: In
      this case-control study, we used a socio-demographic and clinical variables
      questionnaire to assess random convenient samples of 50 control, 40 and 60 first
      degree relatives of bipolar and epileptic patients, respectively at Federal Neuro
      psychiatric Hospital (FNPH), Maiduguri. Relatives of epileptic patients and the
      control completed the mood disorder questionnaire (MDQ). Two consultant
      psychiatrists made the diagnosis of epilepsy using the ILAE criteria, in
      relatives of bipolar patients and the control. Participants in both groups had no
      EEG. We analysed the data obtained, using EPI-info 7 to report averages and
      associations between categorical variables with Chi-square test, and analysis of
      variance (ANOVA) for parametric data(statistical significance set at p=0.5, two
      tailed). RESULTS: The rate of epilepsy among relatives of bipolar disorder
      compared with control was 15.2% vs. 2.0% (chi(2)=46.08, p<0.001), and that of
      bipolar among relatives of epileptics compared with control was 14.5% vs. 2.1%
      (chi(2)=31.2, p<0.001). Educational status showed significant relationship across
      two groups (chi(2)=24.19, p=0.0001). Using ANOVA, age showed significant
      relationship among relatives of bipolar and epileptic patients (F=5.769,
      p=0.0039). CONCLUSION: Despite its limitations, this preliminary study
      contributes to literature on the relationship between epilepsy and bipolar
      affective disorder in sub-Saharan Africa.

PMID- 24751313
TI  - Augmentative therapies do not potentiate the antidepressant-like effects of deep
      brain stimulation in rats.
AB  - BACKGROUND: Clinical trials have shown promising results with the use of
      subcallosal cingulate gyrus deep brain stimulation (DBS) for treatment-resistant
      depression. However, strategies to manage patients who do not respond to this
      therapy have not been explored in detail. In rats, DBS in the ventromedial
      prefrontal cortex (vmPFC) induces a significant antidepressant-like response in
      the forced swim test (FST). We have used this test to investigate potential
      interactions between DBS and clinically used augmentative regimens. METHODS: Rats
      undergoing the FST were treated with vmPFC DBS along with different augmentative
      drugs, namely buspirone, risperidone and pindolol. Locomotor activity was tested
      in an open field. RESULTS: DBS induced a significant reduction in immobility
      scores as compared to saline treated controls. These antidepressant-like effects,
      however, were not potentiated by the co-administration of buspirone, risperidone
      or pindolol. LIMITATIONS: Despite having good predictive validity, animal models
      are limited from a translational perspective. CONCLUSIONS: Our results indicate
      that that the antidepressant-like effects of vmPFC DBS in the FST are not
      enhanced by augmentative therapies.

PMID- 24751314
TI  - Associations between the SS variant of 5-HTTLPR and PTSD among adults with
      histories of childhood emotional abuse: results from two African American
      independent samples.
AB  - BACKGROUND: Prior studies have found that the 5-HTTLPR polymorphism in the
      promoter region of the serotonin transporter gene (SLC6A4) interacts with
      stressful life events to increase general risk for PTSD, but this association has
      not extended to African American samples. Further, little is known about the
      effects of this interaction on specific PTSD symptom clusters, despite
      indications that clusters may have different biological substrates. The current
      study examined the interaction between exposure to childhood emotional abuse and
      5-HTTLPR genotype on risk for PTSD symptom severity and severity of specific PTSD
      symptom clusters in two African American samples. METHODS: Participants were 136
      African American household residents from Detroit, MI and 546 African American
      patients recruited from waiting rooms in primary care clinics in Atlanta, GA.
      Participants reported emotional abuse exposure and PTSD symptom severity, and
      provided DNA for triallelic 5-HTTLPR genotyping. Analysis of covariance (ANCOVA)
      was used to examine main effects and interactions. RESULTS: In both African
      American samples, 5-HTTLPR genotype modified the effect of emotional abuse on
      PTSD symptom severity. Participants with the low-expression SS genotype who were
      exposed to emotional abuse had significantly lower reexperiencing and arousal
      symptom severity scores. LIMITATIONS: The DNHS genetic sample size was small, and
      abuse data were assessed retrospectively. CONCLUSIONS: The SS variant of 5-HTTLPR
      appears to buffer against developing the reexperiencing and arousal symptoms of
      PTSD in two independent African American samples exposed to childhood emotional
      abuse. Findings also highlight the importance of considering emotional abuse
      experiences in patients with suspected PTSD.

PMID- 24751315
TI  - The role of spousal loss in the development of depressive symptoms in the elderly
      - implications for diagnostic systems.
AB  - BACKGROUND: In the revised version of the Diagnostic and Statistical Manual of
      Mental Disorders (DSM) the Mood Disorder Workgroup for DSM-V the bereavement
      exclusion criterion for the diagnosis of major depression has been eliminated.
      AIM: To investigate the impact of bereavement on the incidence of depression and
      depressive symptoms in the elderly. METHOD: Participants over 75 years from the
      longitudinal German Study on Ageing, Cognition, and Dementia in Primary Care
      Patients (AgeCoDe) that were still married at baseline were investigated
      (n=1,193). Data from four follow-ups (time frame: 6 years) were investigated. The
      response rate at baseline was 50.3%. Three clinical endpoints were analyzed:
      depressive symptoms according to Geriatric Depression Scale (1) GDS>=6, (2)
      GDS>=10, and (3) Major Depression (MD). The effect of loss was investigated using
      random-effects regression models. RESULTS: Experiencing a loss of spouse was
      predictive of a higher incidence in GDS>=6 (OR 4.52, 95% CI 2.6-7.9) and 10 (OR
      5.59, 95% CI 1.8-17.0) even after adjusting for age, gender, impairment at
      baseline, and GDS score at baseline. Associations with MD were not significant
      (OR 1.77, 96% CI 0.9-3.5). CONCLUSIONS: Older adults experiencing the loss of
      their spouse are more likely to display elevated levels of depressive symptoms,
      that may reach a concerning level of severity.

PMID- 24751316
TI  - Association between family history of mood disorders and clinical characteristics
      of bipolar disorder: results from the Brazilian bipolar research network.
AB  - OBJECTIVES: To compare clinical characteristics of bipolar disorder (BD) in
      patients with and without a family history of mood disorders (FHMD) in a large
      sample from the Brazilian Research Network of Bipolar Disorders. METHODS: Four
      hundred eighty-eight DSM-IV BD patients participating in the Brazilian Research
      Network of Bipolar Disorders were included. Participants were divided between
      those with FHMD (n=230) and without FHMD (n=258). We compared these two groups on
      demographic and clinical variables and performed a logistic regression to
      identify which variables were most strongly associated with positive family
      history of mood disorders. RESULTS: BD patients with FHMD presented with
      significantly higher lifetime prevalence of any anxiety disorder, obsessive
      compulsive disorder, social phobia, substance abuse, and were more likely to
      present history of suicide attempts, family history of suicide attempts and
      suicide, and more psychiatric hospitalizations than BD patients without FHMD.
      Logistic regression showed that the variables most strongly associated with a
      positive FHMD were any comorbid anxiety disorder, comorbid substance abuse, and
      family history of suicide. LIMITATIONS: Cross-sectional study and verification of
      FHMD by indirect information. CONCLUSION: BD patients with FHMD differ from BD
      patients without FHMD in rates of comorbid anxiety disorder and substance abuse,
      number of hospitalizations and suicide attempts. As FHMD is routinely assessed in
      clinical practice, these findings may help to identify patients at risk for
      particular manifestations of BD and may point to a common, genetically determined
      neurobiological substrate that increases the risk of conditions such as
      comorbidities and suicidality in BD patients.

PMID- 24751317
TI  - Association of affective temperaments measured by TEMPS-a with cognitive deficits
      in patients with bipolar disorder.
AB  - BACKGROUND: Affective temperaments such as cyclothymia, which may be the
      fundamental substrates for bipolar disorder and bipolar II in particular, have
      been reported to be associated with abnormalities in the regions that are related
      to cognitive deficits in bipolar disorder. However, few studies have examined the
      effects of affective temperaments on neuropsychological performance in
      individuals with bipolar disorder. METHOD: In a six-week prospective study, we
      administered Chinese version of TEMPS-A (Temperament Evaluation of Memphis, Pisa,
      San Diego-Autoquestionnair) to 93 patients with bipolar I depression, 135
      patients with bipolar II depression, and 101 healthy controls. Cognitive function
      was assessed with a battery of neuropsychological tasks, including attention,
      processing speed, set shifting, planning, verbal working memory, verbal fluency,
      and visual spatial memory. Mixed-effects statistical models were used to assess
      the effects of affective temperaments on cognitive function. RESULTS: Bipolar
      patients with hyperthymic temperament showed greater cognitive deficits in set
      shifting (p=0.05) and verbal working memory (p=0.026) than did bipolar patients
      with non-predominant temperaments (predominant temperament was defined as one
      standard deviation above the mean). The differences in estimated marginal means
      were -0.624 (95% CI, -1.25 to 0) and -0.429 (95% CI, -0.81 to -0.05),
      respectively. Significant temperament X bipolar subtype interaction effects were
      observed for set shifting (Wald X(2)=18.161, p<0.001), planning (Wald X(2)=7.906,
      p=0.048), and visual spatial memory (Wald X(2)=16.418, p=0.001). LIMITATION: The
      anxious temperament was not evaluated. CONCLUSION: Our data suggest that
      hyperthymic temperament may be associated with cognitive deficits in some
      specific domains in bipolar disorder; and that the effect of temperaments may be
      different across subtypes of bipolar disorder.

PMID- 24751319
TI  - Both body weight and BMI predicts improvement in symptom and functioning for
      patients with major depressive disorder.
AB  - BACKGROUND: Obesity has shown a positive association with depression. We aimed to
      investigate the relationships among body weight, body mass index (BMI=kg/m(2)),
      change in a depression rating scale, and change in a functional scale with
      fluoxetine treatment for hospitalized patients with major depressive disorder
      (MDD). METHODS: A total of 131 acutely ill inpatients with MDD were enrolled to
      receive 20mg of fluoxetine daily for 6 weeks. The 17-item Hamilton Depression
      Rating Scale (HAMD-17) for symptom and the Work and Social Adjustment Scale
      (WSAS) for functioning were assessed at weeks 0, 1, 2, 3, 4, and 6. Remission was
      defined as a score of<=7 on the HAMD-17 at endpoint. Body weight, body length,
      and BMI were measured at baseline. Pearson correlation coefficients (r) were
      calculated among body weight, BMI, HAMD-17 score change, and WSAS score change.
      RESULTS: Of the 131 participants, 126 (96.2%) had at least one post-baseline
      assessment and were included in the analysis. Significant differences in body
      weight and BMI existed between remitters and nonremitters. There were
      statistically significant relationships among baseline body weight, baseline BMI,
      HAMD-17 score change, and WSAS score change at end point. LIMITATIONS: This is a
      short-term trial with relatively small sample size. CONCLUSIONS: Nonremitters had
      greater body weight and BMI before treatment. Increased body weight and BMI is
      correlated with the decreased improvement in symptom and functioning at end
      point. Depression and obesity should be treated concurrently to optimize clinical
      outcomes for the treatment of depression.

PMID- 24751318
TI  - Risk for suicidal behaviors associated with PTSD, depression, and their
      comorbidity in the U.S. Army.
AB  - BACKGROUND: Suicide rates have risen considerably in the United States Army in
      the past decade. Suicide risk is highest among those with past suicidality
      (suicidal ideation or attempts). The incidence of posttraumatic stress disorder
      (PTSD) and depressive illnesses has risen concurrently in the U.S. Army. We
      examined the relationship of PTSD and depression, independently and in
      combination, and rates of past-year suicidality in a representative sample of
      U.S. Army soldiers. METHODS: This study used the DoD Survey of Health Related
      Behaviors Among Active Duty Military Personnel (DoD HRB) (N=5927). Probable PTSD
      and depression were assessed with the PTSD Checklist (PCL) and the 10-item short
      form of the Center for Epidemiologic Studies Depression Scale (CES-D),
      respectively. Past-year suicidality was assessed via self-report. RESULTS: Six
      percent of Army service members reported suicidality within the past year. PTSD
      and MDD were each independently associated with past-year suicidality. Soldiers
      with both disorders were almost three times more likely to report suicidality
      within the past year than those with either diagnosis alone. Population
      attributable risk proportions for PTSD, depression, and both disorders together
      were 24%, 29%, and 45%, respectively. LIMITATIONS: The current study is subject
      to the limitations of a cross-sectional survey design and the self-report nature
      of the instruments used. CONCLUSIONS: PTSD and depression are each associated
      with suicidality independently and in combination in the active duty component of
      the U.S. Army. Soldiers presenting with either but especially both disorders may
      require additional outreach and screening to decrease suicidal ideation and
      attempts.

PMID- 24751320
TI  - Predictive value of baseline resistance in early response to antidepressants.
AB  - BACKGROUND: Major Depressive Disorder (MDD) is the 3rd source for burden
      worldwide according to the World Health Organization (WHO). This comes partly
      from unsatisfactory response rates after usual treatment, highlighting the need
      for early indicators such as early improvement of depressive symptoms to adapt
      treatment strategies, especially for severe inpatients. Thus our objective was to
      assess the predictive value of baseline partial resistance in early
      antidepressant response (EAR), hypothesizing that previous treatment failures
      would decrease the probability of early response. METHODS: We included 122
      consecutive inpatients with current unipolar MDE. The Mini-Neuropsychiatric
      Interview was used to ascertain DSM-IV diagnoses of MDD as well as psychiatric
      comorbidities, and to exclude patients with a history of bipolar disorder. A
      specifically designed questionnaire was used to collect data on previous
      treatment trials for the current episode so as to generate scores on the five
      existing methods for quantifying treatment resistance. We prospectively assessed
      EAR, defined as a 50% decrease in MADRS after 14 days of steady regimen of
      antidepressant. RESULTS: In the per protocol sample (N=76), multivariate analyses
      showed that psychotic features at baseline remained an independent predictor of
      absence of EAR (p<.01), unlike baseline partial resistance, which may rather be
      associated with a lack of any improvement. LIMITATIONS: Lack of data about
      further response and non-randomized treatment allocation. CONCLUSION: Available
      methods for quantifying treatment resistance are heterogeneous and do not predict
      short-term response among severely depressed inpatients, despite potential
      usefulness in predicting a lack of early improvement.

PMID- 24751321
TI  - Commonalities in grief responding across bereavement and non-bereavement losses.
AB  - BACKGROUND: Despite implications for theory and treatment, commonality in
      responding to non-bereavement and bereavement losses are not well explicated.
      METHOD: This study identified the factor structure of the three most common
      responses to bereavement, prolonged grief, posttraumatic stress, and major
      depression in a bereaved community sample (n=151, 59% female, 68% white) from the
      U.S. recruited from Amazon's MTurk using a cross-sectional survey design, then
      cross-validated the structure in samples where people had lost other potentially
      self-defining roles; one's employment (n=157, 47% female, 69% white) and one's
      marriage (n=116, 62% female, 80% white). RESULTS: Results indicated that symptoms
      of prolonged grief, posttraumatic stress, and major depression were distinct
      factors in the bereaved sample, the three-factor solution was a good fit for the
      job-loss and divorce samples, and levels of grief in each sample appeared to be
      best predicted by time since loss and centrality of the loss to one's identity.
      LIMITATIONS: Limitations include potential sample bias due to convenience
      sampling, and the cross-sectional design did not allow examination of the
      stability of factors over time. CONCLUSIONS: These results suggest that grief is
      not a unique response to loss of loved one but instead may be a common
      phenomenology across types of loss. This implies that facilitating meaningful
      engagement in self-defining activities that compensate for the disrupting loss
      might be efficacious in promoting grief resolution without the need for working
      through individuals' emotional attachment to a specific individual or processing
      one's emotional responses to the loss.

PMID- 24751322
TI  - Discrepancy between self- and observer-rated depression severities as a predictor
      of vulnerability to suicide in patients with mild depression.
AB  - BACKGROUND: Discrepancies in depression severity between the Hamilton Depression
      Rating Scale (HAMD) and the Beck Depression Inventory (BDI) have been reported.
      However, whether these discrepancies impact vulnerability to suicide in patients
      with major depressive disorder (MDD) remains unclear. METHODS: Patients with mild
      MDD (n=161) were enrolled in the study and divided into the following 3 groups:
      (1) patients with MDD with the discrepancy (n=45), i.e., those with low HAMD17
      scores (8-13) and high BDI-II scores (>=29), (2) patients with MDD without the
      discrepancy (n=46), i.e., those with low HAMD17 scores and low BDI-II scores
      (<=28), and (3) patients not currently depressed (n=70), i.e., those with HAMD17
      scores <=7 (affective controls). We examined the relationship of demographic,
      clinical, and neuropsychological variables with any discrepancy between self
      rating and observer rating. RESULTS: Patients with MDD with the discrepancy had
      significantly higher hopelessness than those without the discrepancy and
      affective controls. Verbal fluency task performance of patients with MDD with the
      discrepancy was significantly impaired compared with that of those without the
      discrepancy and affective controls. Stepwise logistic regression analysis
      revealed that a history of suicide attempt [odds ratio (OR), 3.57; 95% confidence
      interval (CI), 1.12-11.37] and hopelessness (OR, 1.23; 95% CI, 1.09-1.38)
      increased odds of the discrepancy. LIMITATIONS: Results require replication.
      CONCLUSIONS: Clinicians should examine discrepancies between self- and observer
      rated depression severities, which are associated with vulnerability to suicide
      in patients with MDD, even if objectively evaluated as mild.

PMID- 24751323
TI  - Male sexual function can be maintained without aromatization: randomized placebo
      controlled trial of dihydrotestosterone (DHT) in healthy, older men for 24
      months.
AB  - INTRODUCTION: Male sexual function is highly androgen dependent but whether
      aromatization of testosterone (T) to estradiol is required remains contentious.
      AIM: This study aims to investigate the effects of selective estrogen deficiency
      induced by a nonaromatizable androgen, dihydrotestosterone (DHT), on sexual
      function of healthy middle-aged and older men. METHODS: Randomized clinical trial
      of daily transdermal DHT (70 mg) or placebo gel treatment in 114 healthy middle
      aged and older (>50 years, mean 60.5 years) men without known prostate disease
      maintaining selective estrogen deficiency for 24 months. OUTCOME MEASURES AND
      ANALYSIS: The end points were responses to a psychosexual and mood questionnaire
      completed before, at 3 months, then at 6 monthly intervals during and 3 months
      after study. Data were analyzed by mixed model analysis of variance for repeated
      measures using age and body mass index (BMI) as covariates and including
      interactions of treatment with age and time-on-study. RESULTS: DHT treatment
      increased serum DHT with complete suppression of serum T, luteinizing hormone,
      follicle stimulating hormone, and estradiol throughout the 24-month study
      resulting in reduced spinal bone density. There were no spontaneous complaints,
      or discontinuations for, adverse effects on sexual function during the study. DHT
      administration had no effects on any of 33 measures of sexual function and mood,
      apart from a mild, but significant decrease in overall sexual desire, which was
      reversible after cessation of treatment. Increasing age and less often increasing
      BMI were associated with significant decreases in most aspects of sexual
      function. CONCLUSIONS: We conclude that aromatization plays only a minimal role
      in maintenance of sexual function in healthy eugonadal middle-aged or older men,
      but age and obesity are significantly associated with decreases in most aspects
      of self-reported sexual function and satisfaction. The dependence of male sexual
      function on aromatization may be conditional on age and obesity and can be
      overcome by a nonaromatizable androgen.

PMID- 24751324
TI  - Establishment of a liver fibrosis model in cynomolgus monkeys.
AB  - Hepatic fibrosis, resulted from hepatoxicity and other diseases such as diabetes,
      is an important pathological characteristic of chronic liver diseases.
      Establishment of hepatic fibrosis animal models is of great importance and a
      prerequisite for human clinical studies. The common models for liver fibrosis are
      often established in lower small animals such as rats, but non-human primates are
      a much better model for human diseases because of the physiological similarity
      with humans. In this study, we investigated the method to induce liver fibrosis
      in cynomolgus monkeys using carbon tetrachloride (CCl4) and to establish a model
      that more closely mimics human liver fibrosis. We successfully established the
      liver fibrosis model in 15 of the 20 cynomolgus monkeys (success rate 75%), by
      CCl4 administration at a dose of 1.0 mL/kg (400 mL/L) twice a week. Liver biopsy
      showed that liver fibrosis progressed with time and gradually advanced into early
      stage cirrhosis in 10 of the 15 established models at 16 weeks. Our study
      provides a better research platform for the prevention and treatment of chronic
      liver diseases.

PMID- 24751325
TI  - Novel nikkomycin analogues generated by mutasynthesis in Streptomyces
      ansochromogenes.
AB  - BACKGROUND: Nikkomycins are competitive inhibitors of chitin synthase and inhibit
      the growth of filamentous fungi, insects, acarids and yeasts. The gene cluster
      responsible for biosynthesis of nikkomycins has been cloned and the biosynthetic
      pathway was elucidated at the genetic, enzymatic and regulatory levels. RESULTS:
      Streptomyces ansochromogenes DeltasanL was constructed by homologous
      recombination and the mutant strain was fed with benzoic acid, 4-hydroxybenzoic
      acid, nicotinic acid and isonicotinic acid. Two novel nikkomycin analogues were
      produced when cultures were supplemented with nicotinic acid. These two compounds
      were identified as nikkomycin Px and Pz by electrospray ionization mass
      spectrometry (ESI-MS) and nuclear magnetic resonance (NMR). Bioassays against
      Candida albicans and Alternaria longipes showed that nikkomycin Px and Pz
      exhibited comparatively strong inhibitory activity as nikkomycin X and Z produced
      by Streptomyces ansochromogenes 7100 (wild-type strain). Moreover, nikkomycin Px
      and Pz were found to be more stable than nikkomycin X and Z at different pH and
      temperature conditions. CONCLUSIONS: Two novel nikkomycin analogues (nikkomycin
      Px and Pz) were generated by mutasynthesis with the sanL inactivated mutant of
      Streptomyces ansochromogenes 7100. Although antifungal activities of these two
      compounds are similar to those of nikkomycin X and Z, their stabilities are much
      better than nikkomycin X and Z under different pHs and temperatures.

PMID- 24751326
TI  - Influenza A subtype H3 viruses in feral swine, United States, 2011-2012.
AB  - To determine whether, and to what extent, influenza A subtype H3 viruses were
      present in feral swine in the United States, we conducted serologic and virologic
      surveillance during October 2011-September 2012. These animals were periodically
      exposed to and infected with A(H3N2) viruses, suggesting they may threaten human
      and animal health. 

PMID- 24751327
TI  - Protein-bound uremic toxins, inflammation and oxidative stress: a cross-sectional
      study in stage 3-4 chronic kidney disease.
AB  - BACKGROUND AND AIMS: Indoxyl sulfate (IS) and p-cresyl sulfate (PCS) are nephro-
      and cardiovascular toxins, produced solely by the gut microbiota, which have pro
      inflammatory and pro-oxidative properties in vitro. We undertook this study to
      investigate the associations between IS and PCS and both inflammation and
      oxidative stress in the chronic kidney disease (CKD) population. METHODS: In this
      cross-sectional observational cohort study, participants with stage 3-4 CKD who
      enrolled in a randomized controlled trial of cardiovascular risk modification
      underwent baseline measurements of serum total and free IS and PCS (measured by
      ultraperformance liquid chromotography), inflammatory markers (interferon gamma
      [IFN-gamma], interleukin-6 [IL-6] and tumor necrosis factor-alpha [TNF-alpha]),
      antioxidant and oxidative stress markers (plasma glutathione peroxidase [GPx]
      activity, total antioxidant capacity [TAC] and F2-isoprostanes) and pulse wave
      velocity (PWV), a marker of arterial stiffness. RESULTS: There were 149 CKD
      patients (59% male; age 60 +/- 10 years; 44% diabetic) with a mean eGFR of 40 +/-
      9 mL/min/1.73 m(2) (range 25-59). Serum free and total IS were independently
      associated with serum IL-6, TNF-alpha and IFN-gamma, whereas serum free and total
      PCS were independently associated with serum IL-6 and PWV. Free IS and PCS were
      additionally independently associated with serum GPx but not with TAC or F2
      isoprostanes. CONCLUSIONS: IS and PCS were associated with elevated levels of
      selected inflammatory markers and an antioxidant in CKD patients. PCS was also
      associated with increased arterial stiffness. Inflammation and oxidative stress
      may contribute to the nephro- and cardiovascular toxicities of IS and PCS.
      Intervention studies targeting production of IS and PCS by dietary manipulation
      and the subsequent effect on cardiovascular-related outcomes are warranted in the
      CKD population.

PMID- 24751328
TI  - Visualizing G protein-coupled receptors in action through confocal microscopy
      techniques.
AB  - G protein-coupled receptors constitute one of the most abundant entities in
      cellular communication. Elucidation of their structure and function as well as of
      their regulation began 30-40 years ago and the advance has markedly increased
      during the last 15 years. They participate in a plethora of cell functions such
      as regulation of metabolic fluxes, contraction, secretion, differentiation, or
      proliferation, and in essentially all activities of our organism; these receptors
      are targets of a large proportion of prescribed and illegal drugs. Fluorescence
      techniques have been used to study receptors for many years. The experimental
      result was usually a two-dimensional (2D) micrograph. Today, the result can be a
      spatiotemporal (four-dimensional, 4D) movie. Advances in microscopy, fluorescent
      protein design, and computer-assisted analysis have been of great importance to
      increase our knowledge on receptor regulation and function and create
      opportunities for future research. In this review we briefly depict the state of
      the art of the G protein-coupled receptor field and the methodologies used to
      study G protein-coupled receptor location, trafficking, dimerization, and other
      types of receptor-protein interaction. Fluorescence techniques now permit the
      capture of receptor images with high resolution and, together with a variety of
      fluorescent dyes that color organelles (such as the plasma membrane or the
      nucleus) or the cytoskeleton, allow researchers to obtain a much clearer idea of
      what is taking place at the cellular level. These developments are changing the
      way we explore cell communication and signal transduction, permitting deeper
      understanding of the physiological and pathophysiological processes.

PMID- 24751329
TI  - mRNA expression of IGF-1 and IGF-1R in patients with colorectal adenocarcinoma
      and type 2 diabetes.
AB  - BACKGROUND AND AIMS: Increasing studies show that messenger RNA (mRNA) levels of
      local IGF-system are overexpressed in cancer tissue of patients with colorectal
      cancer (CRC). However, the influence of type 2 diabetes (T2DM) on the expression
      of insulin-like growth factor-1 (IGF-1) and IGF-1 receptor (IGF-1R) mRNA in
      colorectal cancer tissue and adjacent non-cancerous tissue (ANCT) is unknown. The
      aim of this study was to assess mRNA expression of IGF-1 and IGF-1R in paired
      samples of cancer tissue and ANCT between colorectal adenocarcinoma (CA) patients
      with and without T2DM. METHODS: To quantify the levels of IGF-1 and IGF-1R mRNA
      in CA, we analyzed the expression of IGF-1 and IGF-1R mRNA levels in paired
      samples of cancer tissue and ANCT in CA patients with and without T2DM using real
      time reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: mRNA
      levels of IGF-1 and IGF-1R were significantly higher in cancer tissue compared
      with its ANCT in CA patients with and without T2DM. Compared with the CA group,
      significantly higher levels of IGF-1 and IGF-1R mRNA were observed in cancer
      tissue in CA with T2DM group. No significant differences were observed in the
      role of cancer locations, Dukes stages and diabetes duration on mRNA expression
      of IGF-1. After adjusting for age, gender and Dukes stages, multivariate analysis
      indicated IGF-1 mRNA level was a risk factor for prognosis (p <0.05).
      CONCLUSIONS: Our results support the hypothesis that IGF system plays an
      important role in CRC. Further larger studies are needed.

PMID- 24751330
TI  - Role of miR-208 in cardiac fibrosis: prevention or promotion?

PMID- 24751331
TI  - Further experimental studies on a biodegradable adhesive for protection of
      colorectal anastomosis.
AB  - BACKGROUND AND AIMS: Anastomotic leaks (AL) continue to be a devastating
      complication after colorectal surgery. The purpose of this experimental study was
      to confirm if Pebisut(r) applied to intestinal suture lines increases tensile
      strength in the critical days of healing and to evaluate its anti-inflammatory
      properties. METHODS: Bursting pressures and histological evaluation of suture
      lines in dogs were performed, comparing the burst strength with collagen or fatty
      tissue patches with/without Pebisut(r) (patent granted in the USPTO 8,252.333,
      26.01.2006, in the European Union 2,062,602, 01.12.2010, in Canada 2,661,686,
      21.08.2007 and in Mexico P.C.T./MX/a/2009/001737). RESULTS: Pebisut(r)
      significantly increases burst strength in suture lines in long-term procedures
      with both collagen and fat pad patches. The adhesive penetrates rapidly into the
      suture lines, sealing them and progressing towards the intestinal lumen,
      disappearing in 14-20 days. It was well tolerated without any evidence of
      "foreign body" reaction. CONCLUSIONS: Application of the biodegradable adhesive
      Pebisut(r) is easy, well tolerated by mammalian tissues and consistently
      increases the burst strength of suture lines. Therefore, it may provide more
      tensile strength in anastomosis and help protect AL, one of the most serious
      complications in gastrointestinal surgery. If this experimental finding could be
      translated to clinical surgery, the protection of colorectal anastomosis could be
      beneficial to patients. Additionally, this could also have a positive impact on
      the economic expenditures of healthcare systems and patients.

PMID- 24751332
TI  - Reply: Role of thyroid hormones and mir-208 in myocardial remodeling in 5/6
      nephrectomized rats.

PMID- 24751333
TI  - Expression of CD90, CD96, CD117, and CD123 on different hematopoietic cell
      populations from pediatric patients with acute myeloid leukemia.
AB  - BACKGROUND AND AIMS: In trying to contribute to our knowledge on the biology of
      hematopoietic stem cells (HSC) and hematopoietic progenitor cells (HPC) from
      pediatric acute myeloid leukemia (AML), in the present study we analyzed the
      expression of four cell surface antigens relevant to human hematopoiesis-CD90,
      CD96, CD117, and CD123-in bone marrow from pediatric AML patients and normal
      control subjects. METHODS: CD34(+) CD38(-) cells (enriched for HSC) and CD34(+)
      CD38(+) cells (enriched for HPC) were resolved on the basis of CD34 and CD38
      expression. Concomitantly, expression of CD90 and CD96 or CD117 and CD123 was
      assessed by multicolor flow cytometry in each cell population. RESULTS: CD90 and
      CD117 were expressed in a low proportion of CD34(+) CD38(-) and CD34(+) CD38(+)
      cells and no significant differences were observed between normal marrow and AML
      at diagnosis. In contrast, CD96(+) cells and CD123(+) cells were found at
      significantly higher levels in both cell populations from AML at diagnosis, as
      compared to normal marrow. Levels of both cell surface markers after treatment
      remained higher than in normal marrow. DISCUSSION: These results show an
      increased frequency of CD96(+) and CD123(+) cells within the CD34(+) cell
      population from pediatric AML; this is consistent with the findings reported
      previously for adult AML. Our study supports the notion that expression of such
      antigens should be explored for their use as markers for diagnosis and prognosis.

PMID- 24751334
TI  - Ciprofloxacin-resistant Salmonella enterica serotype Kentucky sequence type 198.

PMID- 24751336
TI  - Genotoxicity and cytotoxicity evaluation of oenothein B and its protective effect
      against mitomycin C-induced mutagenic action.
AB  - The natural product oenothein B (OeB), a dimeric macrocyclic ellagitannin, has a
      wide range of biological activities, such as antioxidant, anti-inflammatory, anti
      viral, antifungal, and antitumor. However, investigations concerning its
      genotoxicity have not been carried out. This study assessed the cytotoxicity,
      genotoxicity, and protective effects of oenothein B using in vitro SOS-Inductest
      and in vivo mouse bone marrow micronucleus (MN) assay through oral and
      intraperitonial routes. In both assays oenothein B did not produce genotoxic
      effects in any of doses tested; in contrast, cytotoxic effect in cells was
      detected only in mice groups treated by both routes and exposed for 24 and 48h.
      Antigenotoxic and anticytotoxic activities of oenothein B were evaluated using
      both assays in combination with mitomycin C (MMC), a bioreductive alkylating
      agent. In the MN assay, a significant reduction was observed in MN frequency in
      all groups co-treated with MMC and OeB compared to those which received only MMC.
      Anticytotoxicity was observed in mice groups exposed to OeB and MMC for 24 and
      48h. In the SOS-Inductest, oenothein B failed to show antigenotoxic and
      anticytotoxic effects; thus, it undoubtedly showed an in vivo protective activity
      against primary DNA damage induced by mitomycin C.

PMID- 24751335
TI  - DNA barcoding provides support for a cryptic species complex within the globally
      distributed and fishery important opah (Lampris guttatus).
AB  - The cornerstone of fisheries management relies on a solid taxonomic base and an
      understanding of how animals can be grouped into coherent management units.
      Surprisingly, little is known about the basic biology and ecology of opah
      (Lampris guttatus), a globally distributed species that is commercially exploited
      and regionally common in the North Pacific. Recent efforts to collect life
      history data on this species uncovered evidence of two North Pacific morphotypes.
      Sequencing of the mitochondrial cytochrome c oxidase I gene (655 bp) for these
      morphotypes and other specimens collected worldwide (n = 480) produced five
      strongly diverged and well-supported clades. Additional sequence data from the
      cytochrome b gene (1141 bp) as well as the nuclear recombination activating gene
      1 (1323 bp) corroborated these results, suggesting these five clades probably
      represent separate species. Our conclusion that opah is a complex of five
      separate species has implications for management and indicates a need to gather
      additional data on these poorly understood fishes.

PMID- 24751337
TI  - Evaluation of the repeated-dose liver micronucleus assay using N
      nitrosomorpholine in young adult rats: report on collaborative study by the
      Collaborative Study Group for the Micronucleus Test (CSGMT)/Japanese
      Environmental Mutagen Society (JEMS)-Mammalian Mutagenicity Study (MMS) Group.
AB  - The present study was conducted to evaluate the suitability of a repeated-dose
      liver micronucleus (LMN) assay in young adult rats as a collaborative study by
      the Mammalian mutagenicity study (MMS) group. All procedures were performed in
      accordance with the standard protocols of the MMS Group. Six-week-old male
      Crl:CD(SD) rats (5 animals/group) received oral doses of the hepatocarcinogen N
      nitrosomorpholine (NMOR) at 0 (control), 5, 10, and 30mg/kg/day (10mL/kg) for 14
      days. Control animals received vehicle (water). Hepatocytes were collected from
      the liver 24h after the last dose, and the number of micronucleated hepatocytes
      (MNHEPs) was determined by microscopy. The number of micronucleated immature
      erythrocytes (MNIMEs) in the femoral bone marrow was also determined. The liver
      was examined using histopathologic methods after formalin fixation. The results
      showed statistically significant and dose-dependent increases in the number of
      MNHEPs in the liver at doses of 10mg/kg and greater when compared with the
      vehicle control. However, no significant increase was noted in the number of
      MNIMEs in the bone marrow at doses of up to 30mg/kg. Histopathology of the liver
      revealed hypertrophy and single cell necrosis of hepatocytes at doses of 5mg/kg
      and above. These results showed that the induction of micronuclei by NMOR was
      detected by the repeated-dose LMN assay, but not by the repeated-dose bone marrow
      micronucleus assay. 

PMID- 24751338
TI  - Left main coronary artery compression syndrome and spontaneous coronary artery
      dissection: coincidence or pathologic association?
AB  - Left main coronary artery compression syndrome (LMCS) in patients with severe
      pulmonary arterial hypertension (PAH) is an unusual, and often a missed cause of
      exertional angina. Spontaneous coronary dissection (SCD) is a rare cause of acute
      coronary syndrome of unknown etiology, with predilection to women in the 20s-40s.
      Weather the co-presence of LMCS and SCD in certain patients is a coincidence or
      of pathological significance is not known. The optimal management strategy of
      each of these conditions remains controversial. We report a case of SCD in a
      patient with PAH and LMCS, successfully treated with conservative medical
      therapy. 

PMID- 24751339
TI  - New onset right ventricular enlargement in recent dyspnea: Is echocardiography
      enough for a diagnosis of pulmonary thrombo-embolism?
AB  - Pulmonary embolism may be often promptly diagnosed just by bedside
      echocardiography, in the case of new onset severe right ventricular enlargement,
      increased pulmonary pressure and dyspnea. However, CT confirmation could be
      required in the presence of contrasting findings during diagnostic work up. We
      report the case of a 79-year old woman who presented with acute dyspnea, right
      ventricular enlargement and leftward septal shift. Despite first diagnosis of
      pulmonary embolism, an irregular mass was detected at CT scan in mid left lung,
      apparently infiltrating left pulmonary artery branches, without signs of evident
      pulmonary thrombo-embolism. Visceral pleural and lymphonodular infiltration
      suspected for malignancy was also present. We hypothesize that acutely increased
      pulmonary pressures and enlarged right ventricle were caused by the infiltrating
      pulmonary mass, presumably a lung tumor, partly involving left pulmonary artery
      branches and by tumor pulmonary embolism. A diagnosis of pulmonary thrombo
      embolism exclusively based on echocardiography may be occasionally misleading
      without a careful diagnostic work-up. 

PMID- 24751340
TI  - Acute limb ischemia due to Candida lusitaniae aortic valve endocarditis.
AB  - We present a case of a 35-year-old male with history of intravenous heroin use,
      who presented with acute limb ischemia and was found to have Candida lusitaniae
      endocarditis. After an urgent intervention to salvage the right lower extremity,
      successful outcome of his infection was achieved by a combined surgical and
      antifungal treatment. 

PMID- 24751341
TI  - Three cases of eruptive collagenoma and a literature review, 1970-2012.

PMID- 24751342
TI  - Complexity and network dynamics in physiological adaptation: an integrated view.
AB  - Living organisms constantly interact with their surroundings and sustain internal
      stability against perturbations. This dynamic process follows three fundamental
      strategies (restore, explore, and abandon) articulated in historical concepts of
      physiological adaptation such as homeostasis, allostasis, and the general
      adaptation syndrome. These strategies correspond to elementary forms of behavior
      (ordered, chaotic, and static) in complex adaptive systems and invite a network
      based analysis of the operational characteristics, allowing us to propose an
      integrated framework of physiological adaptation from a complex network
      perspective. Applicability of this concept is illustrated by analyzing molecular
      and cellular mechanisms of adaptation in response to the pervasive challenge of
      obesity, a chronic condition resulting from sustained nutrient excess that
      prompts chaotic exploration for system stability associated with tradeoffs and a
      risk of adverse outcomes such as diabetes, cardiovascular disease, and cancer.
      Deconstruction of this complexity holds the promise of gaining novel insights
      into physiological adaptation in health and disease. 

PMID- 24751343
TI  - PCL/PEG core/sheath fibers with controlled drug release rate fabricated on the
      basis of a novel combined technique.
AB  - A novel core/sheath fiber preparation method, which included the processes of
      blend electrospinning to produce the core fiber and UV-induced graft
      polymerization to fabricate the outer polymeric shell, was presented to provide
      designated fibers with different shell thicknesses. A hydrophilic drug, salicylic
      acid (SA), was loaded in the representative poly(epsilon-caprolactone)
      (PCL)/polyethylene glycol (PEG) core/sheath fibers, performed according to this
      combined technique. FTIR analysis indicated that the existence of hydrogen bonds
      between SA and the PCL matrix improved drug compatibility. Field emission
      scanning electron microscopy (FESEM) images indicated that the morphology and the
      diameter distribution of fibers changed significantly after the graft
      polymerization procedure. All the core/sheath fibers became more flexible and
      thicker compared with the core fiber. The water contact angle (WCA) test also
      noted the differences of these two fibers: PCL/PEG core/sheath fibers with cross
      linked PEG surface exhibited more hydrophilic property. Moreover, in vitro SA
      release tests were conducted to explore the relationship between the PEG shell
      thickness and the drug release rate. A typical biphasic release mechanism was
      observed for the PCL/PEG core/sheath fibers, and their sustained release rates
      were controlled by the PEG shell thickness in a linear correlation. 

PMID- 24751344
TI  - Injectable long-term control-released in situ gels of hydrochloric thiothixene
      for the treatment of schizophrenia: preparation, in vitro and in vivo evaluation.
AB  - Hydrochloric thiothixene (HT) is an antipsychotic drug used in the treatment of
      various psychoses including schizophrenia, mania, polar disorder, and in behavior
      disturbances. However, because the psychotics often could not control their
      behaviors, the independent administration of antipsychotic drug based on medical
      order was difficult. The omissions of the administration often brought an
      unsatisfactory therapeutic efficacy. A novel injectable long-term control
      released in situ gel of HT for the treatment of schizophrenia was developed based
      on biodegradable material polylactic acid (PLA). The optimum formulation of the
      injectable PLA-based HT in situ gel containing 15% (w/w) HT and 45% (w/w) PLA
      with benzyl benzoate was used as a gelling solvent. The results of the in vitro
      and in vivo studies showed that this in situ gel had a long-term period of drug
      release for several weeks and a good histocompatibility without any remarkable
      inflammatory reactions. 

PMID- 24751345
TI  - Optical microscopy as a comparative analytical technique for single-particle
      dissolution studies.
AB  - Novel, simple and cost effective methods are needed to replace advanced chemical
      analytical techniques, in small-scale dissolution studies. Optical microscopy of
      individual particles could provide such a method. The aim of the present work was
      to investigate and verify the applicability of optical microscopy as an
      analytical technique for drug dissolution studies. The evaluation was performed
      by comparing image and chemical analysis data of individual dissolving particles.
      It was shown that the data obtained by image analysis and UV-spectrophotometry
      produced practically identical dissolution curves, with average similarity and
      difference factors above 82 and below 4, respectively. The relative standard
      deviation for image analysis data, of the studied particle size range, varied
      between 1.9% and 3.8%. Consequently, it is proposed that image analysis can be
      used, on its own, as a viable analytical technique in single-particle dissolution
      studies. The possibility for significant reductions in sample preparation,
      operational cost, time and substance consumption gives optical detection a clear
      advantage over chemical analytical methods. Thus, image analysis could be an
      ideal and universal analytical technique for rapid small-scale dissolution
      studies. 

PMID- 24751346
TI  - Investigation of drug-polymer interaction in solid dispersions by vapour sorption
      methods.
AB  - The objective of this study was to investigate the effect of different polymeric
      carriers in solid dispersions with an active pharmaceutical ingredient (API) on
      their water vapour sorption equilibria and the influence of the API-polymer
      interactions on the dissolution rate of the API. X-ray diffraction, scanning
      electron microscopy (SEM), moisture sorption analysis, infrared (IR) spectroscopy
      and dissolution tests were performed on various API-polymer systems (Valsartan as
      API with Soluplus, PVP and Eudragit polymers) after production of amorphous solid
      dispersions by spray drying. The interactions between the API and polymer
      molecules caused the water sorption isotherms of solid dispersions to deviate
      from those of ideal mixtures. The moisture sorption isotherms were lower in
      comparison with the isotherms of physical mixtures in all combinations with
      Soluplus and PVP. In contrast, the moisture sorption isotherms of solid
      dispersions containing Eudragit were significantly higher than the corresponding
      physical mixtures. The nature of the API-polymer interaction was explained by
      shifts in the characteristic bands of the IR spectra of the solid dispersions
      compared to the pure components. A correlation between the dissolution rate and
      the water sorption properties of the API-polymer systems has been established. 

PMID- 24751347
TI  - Compounding evidence implicating Western diets in the development of metabolic
      syndrome.

PMID- 24751348
TI  - PCR for detection of oseltamivir resistance mutation in influenza A(H7N9) virus.
AB  - Sensitive molecular techniques are needed for rapid detection of the R292K
      oseltamivir-resistant mutant of influenza A(H7/N9) virus strain to monitor its
      transmission and guide antiviral treatment. We developed a real-time reverse
      transcription PCR and single nucleotide polymorphism probes to differentiate this
      mutant strain in mixed virus populations in human specimens. 

PMID- 24751349
TI  - Comparative uptake of 18F-FEN-DPAZn2, 18F-FECH, 18F-fluoride, and 18F-FDG in
      fibrosarcoma and aseptic inflammation.
AB  - The aim of this study is to evaluate uptake of 2-(18)F-fluoroethyl-bis(zinc(II)
      dipicolylamine) ((18)F-FEN-DPAZn2) as a promising cell death imaging agent, a
      choline analog (18)F-fluoroethylcholine ((18)F-FECH), (18)F-fluoride as a bone
      imaging agent, and a glucose analog 2-(18)F-fluoro-2-deoxy-d-glucose ((18)F-FDG)
      in the combined S180 fibrosarcoma and turpentine-induced inflammation mice
      models. The results showed that (18)F-FDG had the highest tumor-to-blood uptake
      ratio and tumor-to-muscle ratio, and high inflammation-to-blood ratio and
      inflammation-to-muscle ratio. (18)F -FECH showed moderate tumor-to-blood ratio
      and tumor-to-muscle ratio, and low inflammation-to-blood ratio and inflammation
      to-muscle ratio. However, accumulation of (18)F FEN-DPAZn2 in tumor was similar
      to that in normal muscle. Also, (18)F-FEN-DPAZn2 and (18)F-fluoride exhibited the
      best selectivity to inflammation. (18)F-FECH positron emission tomography (PET)
      imaging demonstrates some advantages over (18)F-FDG PET for the differentiation
      of tumor from inflammation. (18)F FEN-DPAZn2 and (18)F-fluoride can be used for
      PET imaging of aseptic inflammation. 

PMID- 24751350
TI  - The radiation damage of crystalline silicon PN diode in tritium beta-voltaic
      battery.
AB  - A tritium beta-voltaic battery using a crystalline silicon convertor composed of
      (100)Si/SiO2/Si3N4 film degrades remarkably with radiation from a high intensity
      titanium tritide film. Simulation and experiments were carried out to investigate
      the main factor causing the degradation. The radiation damages mainly comes from
      the x-ray emitted from the titanium tritide film and beta particle can relieve
      the damages. The x-ray radiation induced positive charges in the SiO2 film
      destroying the output property of the PN diode with the induction of an electric
      field. 

PMID- 24751351
TI  - Evaluation of plating conditions for the recovery of 210Po on a Ag planchet.
AB  - The polonium-210 in the sea and its radiological consequences have been widely
      studied. Current processes for (210)Po recovery from seawater vary significantly.
      We compared selected processes to determine optimal conditions for recovery in
      modestly equipped laboratories. Plating (210)Po onto a Ag planchet with constant
      stirring for 15 h at room temperature after preconcentration from seawater
      samples with Mn was preferred, achieving more than 96% recovery with 3% or less
      precision. Possible contaminants were masked only by ascorbic acid treatment.

PMID- 24751352
TI  - High levels of sulphadoxine-pyrimethamine resistance Pfdhfr-Pfdhps quintuple
      mutations: a cross sectional survey of six regions in Tanzania.
AB  - BACKGROUND: In 2006, the first-line anti-malarial drug treatment in Tanzania was
      changed from sulphadoxine-pyrimethamine (SP) to artemether-lumefantrine (ALu), an
      artemisinin-based combination (ACT), since when the use of SP has been restricted
      for intermittent preventive treatment in pregnancy (IPTp). A number of Plasmodium
      falciparum mutations are known to be associated with resistance to SP, but it is
      not known if the prevalence of these mutations is increasing or decreasing under
      the conditions of reduced levels of SP use. This study reports on the current SP
      resistant quintuple Pfdhfr-Pfdhps mutations in six regions of Tanzania. METHODS:
      Finger-prick blood on filter paper and rapid diagnostic test strips from P.
      falciparum-positive individuals of all age groups attending health facilities in
      six regions of Tanzania between June 2010 and August 2011 were obtained. Using
      chelex-100 extracted DNA, genotyping was done for mutations on codons 51, 59 and
      108 of Pfdhfr and 437 and 540 of Pfdhps genes using PCR-RFLP technique. RESULTS:
      A total of 802 malaria-positive samples were screened and genotyped. The
      prevalence of Pfdhfr 51I, Pfdhps 437G and 540E varied between the regions (p <
      0.001) whereas Pfdhfr 59R (FE 10.79, p = 0.225) and 108 N (FE 10.61, p = 0.239)
      did not vary between the regions. The Pfdhfr triple mutant was above 84% and
      close to fixation levels in all regions, whereas the Pfdhps double mutation
      ranged from 43.8 to 97% between the regions. The quintuple mutant (IRNGE) was the
      most prevalent in all regions and it varied significantly from 37.5 to 90.2%
      (chi(2) = 1.11, p <0.001). CONCLUSIONS: There is evidence of persistent high
      levels of SP resistance markers in Tanzania with evidence of quintuple mutations
      that are likely to become fixed in the population. This threatens the future of
      SP not only in IPTp programmes, but as a combination drug for ACT. Continuous
      monitoring of SP-IPTp efficacy should be encouraged subsequent to searching for
      alternative drugs for IPTp in East Africa.

PMID- 24751353
TI  - Unique strain of Crimean-Congo hemorrhagic fever virus, Mali.

PMID- 24751354
TI  - Re: Fazal A, Yoo A, Bendo JA. Does the presence of the nerve root sedimentation
      sign on MRI correlate with the operative level in patients undergoing posterior
      lumbar decompression for lumbar stenosis? Spine J 2013;13:837-42.

PMID- 24751355
TI  - Editorial overview: Lymphocyte activation and effector functions.

PMID- 24751356
TI  - Zinc transporter 8 (ZnT8) and beta cell function.
AB  - Human pancreatic beta cells have exceptionally high zinc content. In beta cells
      the highest zinc concentration is in insulin secretory granules, from which it is
      cosecreted with the hormone. Uptake of zinc into secretory granules is mainly
      mediated by zinc transporter 8 (ZnT8), the product of the SLC30A8 [solute carrier
      family 30 (zinc transporter), member 8] gene. The minor alleles of several single
      nucleotide polymorphisms (SNPs) in SLC30A8 are associated with decreased risk of
      type 2 diabetes (T2D), but the precise mechanisms underlying the protective
      effects remain uncertain. In this article we review current knowledge of the role
      of ZnT8 in maintaining zinc homeostasis in beta cells, its role in glucose
      metabolism based on knockout mouse studies, and current theories regarding the
      link between ZnT8 function and T2D. 

PMID- 24751358
TI  - How phonetically selective is the human auditory cortex?
AB  - Responses in the human auditory cortex to natural speech reveal a dual character.
      Often they are categorically selective to phonetic elements, serving as a gateway
      to abstract linguistic representations. But at other times they reflect a
      distributed generalized spectrotemporal analysis of the acoustic features, as
      seen in early mammalian auditory cortices. 

PMID- 24751357
TI  - G protein-coupled receptors and the regulation of autophagy.
AB  - Autophagy is an important catabolic cellular process that eliminates damaged and
      unnecessary cytoplasmic proteins and organelles. Basal autophagy occurs during
      normal physiological conditions, but the activity of this process can be
      significantly altered in human diseases. Thus, defining the regulatory inputs and
      signals that control autophagy is essential. Nutrients are key modulators of
      autophagy. Although autophagy is generally accepted to be regulated in a cell
      autonomous fashion, recent studies suggest that nutrients can modulate autophagy
      in a systemic manner by inducing the secretion of hormones and neurotransmitters
      that regulate G protein-coupled receptors (GPCRs). Emerging studies show that
      GPCRs also regulate autophagy by directly detecting extracellular nutrients. We
      review the role of GPCRs in autophagy regulation, highlighting their potential as
      therapeutic drug targets. 

PMID- 24751359
TI  - Crossmodal shaping of pain: a multisensory approach to nociception.
AB  - Noxious stimuli in our environment are often accompanied by input from other
      sensory modalities that can affect the processing of these stimuli and the
      perception of pain. Stimuli from these other modalities may distract us from pain
      and reduce its perceived strength. Alternatively, they can enhance the saliency
      of the painful input, leading to an increased pain experience. We discuss factors
      that influence the crossmodal shaping of pain and highlight the important role of
      innocuous stimuli in peripersonal space. We propose that frequency-specific
      modulations in local oscillatory power and in long-range functional connectivity
      may serve as neural mechanisms underlying the crossmodal shaping of pain.
      Finally, we provide an outlook on future directions and clinical implications of
      this promising research field. 

PMID- 24751360
TI  - Prevention of venous thromboembolism in adult patients with cancer in the acute
      care setting.
AB  - Adult patients with cancer in the acute care setting face numerous potential
      complications related to malignancy. Risk for development of venous
      thromboembolism (VTE) is among the most critical of adverse outcomes for this
      patient population, ultimately leading to increased morbidity and mortality
      rates. Nurses must be familiar with the general pathophysiology of VTE and
      pathophysiology specific to oncology to prevent the occurrence of this complex
      hematologic process. Knowledge of pharmacologic prevention methods, such as low
      dose unfractionated heparin, low-molecular weight heparin, and warfarin, as well
      as mechanical prophylaxis such as graduated compression stockings and
      intermittent pneumatic compression devices, is essential to preventing VTE. The
      ability to develop and implement an educational plan tailored to the specific
      learning needs of each patient also is a vital skill that must be incorporated
      into the practice of nurses caring for patients with cancer in the acute care
      setting to prevent the incidence of VTE in this population. 

PMID- 24751361
TI  - Tirofiban induces VEGF production and stimulates migration and proliferation of
      endothelial cells.
AB  - Tirofiban is a fibrinogen receptor antagonist, generated using the tripeptide Arg
      Gly-Asp (RGD) as a template. RGD activates integrin receptors and integrin
      mediated signals are necessary for normal cells to promote survival and stimulate
      cell cycle progression. We investigated whether tirofiban activated growth
      stimulatory signals in endothelium. For this study human umbilical vein
      endothelial cells (HUVEC) and human aortic endothelial cells (HAEC) were used.
      Analysis of cell proliferation, by cell counts, showed that the number of
      endothelial cells doubled after 72 h of culture in the absence of tirofiban,
      while they were tripled and even quadrupled, in the presence of increasing doses
      of the drug. Moreover, tirofiban-stimulated cells had a greater ability to
      migrate through the transwell filters of Boyden chamber, compared to unstimulated
      cells. The scratch assay, which mimics cell migration during wound healing,
      showed that tirofiban stimulated HUVECs to migrate into the leading hedge of the
      scratch. Western blot showed that tirofiban increased the expression levels of
      VEGF and the downstream effectors Erk and cyclin D. An inhibitor of VEGFR2
      counteracted tirofiban-induced-proliferation, suggesting a role for VEGF in such
      effect. Our study shows that tirofiban stimulates the migration and proliferation
      of endothelial cells suggesting that it can promote endothelial repair. Ex vivo
      cultures of arterial rings confirmed the growth stimulatory effect of tirofiban
      on endothelium. Thus, the benefits of tirofiban in those with acute coronary
      syndromes undergoing PTCA may be due to rapid endothelization of damaged vessel,
      besides antiplatelet effects.

PMID- 24751362
TI  - Lipid-lowering effects of Danhong injection on hyperlipidemia rats.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Danhong injection (DHI), a Chinese medical
      product extracted from Radix et Rhizoma Salviae Miltiorrhizae (Salvia
      miltiorrhiza Bge., Labiatae, Danshen in Chinese) and Flos Carthami (Carthamus
      tinctorius L., Compositae, Honghua in Chinese), has been reported to have anti
      inflammatory, anti-oxidative and anti-fibrinolytic properties and is used
      extensively for the clinical treatment of cardiovascular disease in clinic. This
      study aimed to investigate the preventive and therapeutic effects of DHI on
      hyperlipidemia. MATERIALS AND METHODS: Forty-eight adult male Sprague-Dawley rats
      were randomly divided into four groups: normal control (NC), model control (MC)
      and DHI-treated at doses of 1.0mL/kg and 2.0mL/kg. The effects of DHI on serum
      triglyceride (TG), total cholesterol (TC), glucose, high density lipoprotein
      cholesterol (HDL-C) and low density lipoprotein cholesterol (LDL-C) were
      evaluated and insulin was determined by enzyme-linked immunosorbent assay
      (ELISA). Moreover, the expression of acetyl-CoA carboxylase 1 (ACC1), fatty acid
      synthase (FAS), carnitine palmitoyl transferase 1 (CPT1), hydroxymethylglutaryl
      CoA reductase (HMGR) and peroxisome proliferator-activated receptor alpha (PPAR
      alpha) in liver were determined by real-time PCR. RESULTS: Compared with the MC
      group, rats treated with DHI had significantly reduced TG, TC, LDL-C and
      arteriosclerosis index (AI). Expression of FAS and HMGR mRNA was significantly
      reduced, whereas the CPT1 and PPAR-alpha were significantly increased.
      CONCLUSION: DHI treatment was accompanied by significantly increased lipolysis in
      the liver and decreased fatty acid synthesis. The insights gained from this study
      will improve both understanding of the mechanisms involved in the effect of DHI
      on hyperlipidemia and the pharmacological rationale for the use of DHI in
      diseases caused by lipid metabolic disorders.

PMID- 24751363
TI  - Topical application of Kochia scoparia inhibits the development of contact
      dermatitis in mice.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Kochia scoparia (Chenopodiaceae) has been
      reported to have anti-nociceptive, anti-inflammatory, anti-allergic, and anti
      pruritic actions. This study investigated the anti-inflammatory effects of
      externally applied Kochia scoparia water extract (KSW) in 2,4
      dinitrochlorobenzene (DNCB)-induced contact dermatitis mouse model. MATERIALS AND
      METHODS: To develop atopic dermatitis-like skin lesions, 100MUL of 1% DNCB in
      acetone/olive oil (4:1) had been applied for three days on shaved dorsal skin. 1%
      KSW was topically applied to DNCB-induced mice. After KSW treatment, histological
      analysis was measured by hematoxylin eosin staining. The cytokine and pro
      inflammatory expressions were examined using reverse transcription polymerase
      chain reaction and western blotting analysis. RESULTS: Histological studies
      showed that hyperplasia of the epidermis and dermis in the KSW treated group was
      markedly decreased as compared with the DNCB group. The expression levels of pro
      inflammatory cytokine such as IL-1beta, and TNF-alpha mRNA were significantly
      reduced by topical application of KSW, whereas these cytokines were increased in
      DNCB-induced dorsal skin. In addition, NF-kappaB expression was inhibited by KSW
      treatment in DNCB-induced mice. Similarly, KSW treatment significantly suppressed
      the expression of several MAP kinases, including ERK1/2, p38, and JNK compared to
      their expression in DNCB-induced mice. CONCLUSIONS: These findings indicated that
      KSW ameliorates contact dermatitis via inhibition of the production of several
      inflammatory mediators. Therefore, external application of KSW may be used for
      the treatment of contact dermatitis as an alternative therapy.

PMID- 24751364
TI  - Preconditioning with the traditional Chinese medicine Huang-Lian-Jie-Du-Tang
      initiates HIF-1alpha-dependent neuroprotection against cerebral ischemia in rats.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Huang-Lian-Jie-Du-Tang (HLJDT) is a classical
      heat-clearing and detoxicating formula of traditional Chinese medicine that is
      widely used to treat stroke. The present study was designed to investigate the
      effects of HLJDT preconditioning on neurons under oxygen and glucose deprivation
      (OGD) and rats subjected to middle cerebral artery occlusion (MCAO). MATERIALS
      AND METHODS: A stroke model of rats was obtained through MCAO. Following HLJDT
      preconditioning, the cerebral infarction volume, cerebral water content, and
      neurological deficient score were determined. Cerebral cortical neurons cultured
      in vitro were preconditioned with HLJDT and then subjected to OGD treatment. The
      release of lactate dehydrogenase (LDH) from neurons was detected. The levels of
      hypoxia-inducible factor-1alpha (HIF-1alpha) and PI3K/Akt signaling were analyzed
      by western blotting, and the levels of erythropoietin (EPO) and vascular
      endothelial growth factor (VEGF) in the supernatant of the neurons and the plasma
      of MCAO rats were measured through a radioimmunological assay. The apoptosis and
      proliferation of neurons were analyzed by immunohistochemistry. RESULTS: HLJDT
      preconditioning significantly reduced the cerebral infarction volume and cerebral
      water content and ameliorated the neurological deficient score of MCAO rats. In
      addition, HLJDT preconditioning protected neurons against OGD. Increased HIF
      1alpha, EPO, and VEGF levels and the activation of PI3K/Akt signaling were
      observed as a result of HLJDT preconditioning. Furthermore, HLJDT preconditioning
      was found to inhibit ischemia-induced neuron apoptosis and to promote neuron
      proliferation under conditions of ischemia/reperfusion. CONCLUSION: Both rats and
      neurons subjected to HLJDT preconditioning were able to resist
      ischemia/reperfusion or hypoxia injury through the inhibition of apoptosis and
      the enhancement of proliferation, and these effects were primarily dependent on
      the activation of the PI3K/Akt signaling pathway and HIF-1alpha.

PMID- 24751365
TI  - Characterization and neutralization of Nemopilema nomurai (Scyphozoa:
      Rhizostomeae) jellyfish venom using polyclonal antibody.
AB  - Jellyfish stings have often caused serious health concerns for sea bathers
      especially in tropical waters. In the coastal areas of Korea, China and Japan,
      the blooming and stinging accidents of poisonous jellyfish species have recently
      increased, including Nemopilema nomurai. We have generated a polyclonal antibody
      against N. nomurai jellyfish venom (NnV) by the immunization of white rabbits
      with NnV antigen. In the present study, the antibody has been characterized for
      its neutralizing effect against NnV. At first, the presence of NnV polyclonal
      antibody has been confirmed from the immunized rabbit serum by Enzyme linked
      immunosorbent assay (ELISA). Then, the neutralizing activities of the polyclonal
      antibody have been investigated using cell-based toxicity test, hemolysis assay,
      and mice lethality test. When the polyclonal antibody was preincubated with NnV,
      it shows a high effectiveness in neutralizing the NnV toxicities in a
      concentration-dependent manner. Moreover, we explored proteomic analyses using 2
      D SDS-PAGE and MALDI-TOF mass spectrometry to illustrate the molecular identities
      of the jellyfish venom. From this, 18 different protein families have been
      identified as jellyfish venom-derived proteins; the main findings of which are
      matrix metalloproteinase-14, astacin-like metalloprotease toxin 3 precursor. It
      is expected that the present results would have contributed to our understandings
      of the envenomation by N. nomurai, their treatment and some valuable knowledge on
      the pathological processes of the jellyfish stinging.

PMID- 24751366
TI  - Crotoxin from Crotalus durissus terrificus snake venom induces the release of
      glutamate from cerebrocortical synaptosomes via N and P/Q calcium channels.
AB  - Crotoxin (Crtx), the main toxin in the venom of Crotalus durissus terrificus
      snake, is a heterodimer with a basic subunit, CB, and an acidic subunit, CA. CB
      is a phospholipase A2 that depends on CA to specifically bind to the cell
      membrane. This toxin acts in the central nervous system (CNS) causing chronic
      seizure effects and other cytotoxic effects. Here, we report its action on
      glutamate release in rat cerebral cortex synaptosomes. Aiming at a better
      understanding of the mechanism of action of Crtx, calcium channel blockers were
      used and internalization studies were performed in cerebellar granule neurons.
      Our results show that Crtx induces calcium-dependent glutamate release via N and
      P/Q calcium channels. In addition, the CB subunit of Crtx is shown to be
      internalized. This internalization does not depend on the presence of CA subunit
      neither on the PLA2 activity of CB. A correlation between CB internalization and
      glutamate release remains to be established.

PMID- 24751367
TI  - Antibacterial activity of the emerging Fusarium mycotoxins enniatins A, A1, A2,
      B, B1, and B4 on probiotic microorganisms.
AB  - Enniatins (ENs) are secondary metabolites produced by several Fusarium strains,
      chemically characterized as N-methylated cyclohexadepsipeptides. These compounds
      are known to act as antifungal and antibacterial agents, but they also possess
      anti-insect and phytotoxic properties. In this study, the antimicrobial effect of
      pure fractions of the bioactive compounds ENs A, A1, A2, B, B1, and B4 was tested
      towards nine probiotic microrganisms, twenty-two Saccharomyces cerevisiae strains
      and nine Bacillus subtilis strains. Antimicrobial analyses were carried out the
      disc-diffusion method using ENs concentrations ranging from 0.2 to 20,000 ng.
      Plates were incubated for 24 h at 37  degrees C before reading the diameter of
      the inhibition spots. ENs A, A1, A2, B, B1 and B4, were active against several
      microorganisms with inhibition halos ranging from 3 to 12 mm in diameter. The
      most active mycotoxin was the EN A1, which reduced the microbial growth of 8
      strains at the dose of 20,000 ng, with inhibition spots sized between 8 and 12
      mm. ENs B and B4 showed no antimicrobial activity towards the microorganisms
      tested at doses up to 20,000 ng per disc.

PMID- 24751368
TI  - Coxsackievirus A16 encephalitis during obinutuzumab therapy, Belgium, 2013.

PMID- 24751369
TI  - Information-enhancement and goal setting techniques for increasing adaptive
      motivation and decreasing urges to drink alcohol.
AB  - OBJECTIVE: The aim of the study was to determine whether experimental
      manipulation of sense of control would change moderate drinkers' (N=106) task
      specific motivational structure and explicit and implicit determinants of their
      urge to drink alcohol. METHOD: The effects of various levels of information
      enhancement and goal-setting on participants' performance on experimental tasks
      were assessed. Participants were randomly assigned to a high-sense-of-control,
      low-sense-of-control, or no-intervention group. Dependent measures were indices
      derived from a task-specific version of the Personal Concerns Inventory and the
      Shapiro Control Inventory, Alcohol Urge Questionnaire, and alcohol Stroop test.
      RESULTS: At baseline, there were no differences among the groups on any of the
      measures; however, post-experimentally, induced sense of control had led to
      increases in adaptive motivation and decreases in explicit and implicit measures
      of the urge to drink. CONCLUSIONS: The results show that sense of control can be
      experimentally induced. This finding has important clinical implications.

PMID- 24751370
TI  - Novel avian influenza A(H7N9) virus in tree sparrow, Shanghai, China, 2013.
AB  - In spring 2013, influenza A(H7N9) virus was isolated from an apparently healthy
      tree sparrow in Chongming Dongping National Forest Park, Shanghai City, China.
      The entire gene constellation of the virus is similar to that of isolates from
      humans, highlighting the need to monitor influenza A(H7N9) viruses in different
      species. 

PMID- 24751371
TI  - Bullous pemphigoid with IgG anti-LAD-1 antibodies.

PMID- 24751372
TI  - Preschoolers can form abstract rule representations regardless of cognitive
      flexibility.
AB  - The abstractness of rule representations in the pre-switch phase of the
      Dimensional Change Card Sorting (DCCS) task was studied by letting 3- and 4-year
      old children perform a standard DCCS task and a separate generalization task. In
      the generalization task, children were asked to generalize their sorting rules to
      novel stimuli in one of three conditions. In the relevant change condition,
      values of the relevant dimension changed; in the irrelevant change condition,
      values of the irrelevant dimension changed; and in the total change condition,
      values of both dimensions changed. All children showed high performance on the
      generalization task in the relevant change condition, implying an abstract rule
      representation at the level of dimensions ("same colors go together").
      Performance in the relevant change condition was significantly better (and
      faster) than performance in the other two conditions. Children with high
      cognitive flexibility (switchers on the DCCS task) more often switched their
      attention to the irrelevant dimension in the generalization task only if values
      of the irrelevant dimension changed. Children with low cognitive flexibility
      (perseverators) were more often inconsistent in their sorting on the
      generalization task if values of both dimensions changed. The difference in
      performance on the DCCS task between switchers and perseverators seems to result
      from the processes that operate on the learned sorting rules and not from the
      abstractness of the rule representations children have.

PMID- 24751373
TI  - Longitudinal assessment of short-term memory deterioration in a logopenic variant
      primary progressive aphasia with post-mortem confirmed Alzheimer's Disease
      pathology.
AB  - In the field of dementia research, there are reports of neurodegenerative cases
      with a focal loss of language, termed primary progressive aphasia (PPA).
      Currently, this condition has been further sub-classified, with the most recent
      sub-type dubbed logopenic variant (PPA-LV). As yet, there remains somewhat
      limited evaluation of the characteristics of this condition, with no studies
      providing longitudinal assessment accompanied by post-mortem examination.
      Moreover, a key characteristic of the PPA-LV case is a deterioration of
      phonological short-term memory, but again little work has scrutinized the nature
      of this impairment over time. The current study seeks to redress these oversights
      and presents detailed longitudinal examination of language and memory function in
      a case of PPA-LV, with special focus on tests linked to components of
      phonological short-term memory function. Our findings are then considered with
      reference to a contemporary model of the neuropsychology of phonological short
      term memory. Additionally, post-mortem examinations indicated Alzheimer's disease
      type pathology, providing further evidence that the PPA-LV presentation may
      reflect an atypical presentation of this condition. 

PMID- 24751374
TI  - Enhanced current production by Desulfovibrio desulfuricans biofilm in a mediator
      less microbial fuel cell.
AB  - In this study, a mediator-less microbial fuel cell (MFC) inoculated with a
      sulfate-reducing bacterium (SBR), Desulfovibrio desulfuricans, was equipped with
      bare and surface-treated graphite felt electrodes. Electrochemical treatment of
      the anode surface facilitated biofilm formation on the electrode, resulting in
      rapid and enhanced current production. The maximum current density of the treated
      anode was 233+/-24.2mA/m(2), which was 41% higher than that of the untreated
      anode. The electron transfer rate also increased from 2.45+/-0.04 to 3.0+/
      0.02MUmol of electrons/mg of protein.min. Biofilm formation on the treated anode
      was mainly due to the strong hydrogen or peptide bonds between the amide groups
      of bacterial materials (including cytochrome c) and carboxyl groups formed on the
      electrodes. These results provide useful information on direct electron transfer
      by SRB in a mediator-less MFC through cytochrome c and the effects of the
      electrochemical treatment of electrodes on MFC performance. 

PMID- 24751375
TI  - Bioaugmentation of potent acidogenic isolates: a strategy for enhancing
      biohydrogen production at elevated organic load.
AB  - The efficiency of bioaugmentation strategy for enhancing biohydrogenesis at
      elevated organic load was successfully evaluated by augmenting native acidogenic
      microflora with three acidogenic bacterial isolates viz., Bacillus subtilis,
      Pseudomonas stutzeri and Lysinibacillus fusiformis related to phyla Firmicutes
      and Proteobacteria separately. Hydrogen production ceased at 50g COD/l operation
      due to feed-back inhibition. B. subtilis augmented system showed higher H2
      production followed by L. fusiformis, P. stutzeri and control operations,
      indicating the efficacy of Firmicutes as bioaugmentation biocatalyst. Higher VFA
      production with acetic acid as a major fraction was specifically observed with B.
      subtilis augmented system. Shift in metabolic pathway towards acidogenesis
      favoured higher H2 production. FISH analysis confirmed survivability and
      persistence of augmented strains apart from improvement in process performance.
      Bio-electrochemical analysis depicted specific changes in the metabolic activity
      after augmentation which also facilitated enhanced electron transfer. P. stutzeri
      augmented system documented relatively higher COD removal. 

PMID- 24751376
TI  - Practical immunoaffinity-enrichment LC-MS for measuring protein kinetics of low
      abundance proteins.
AB  - BACKGROUND: For a more complete understanding of pharmacodynamic, metabolic, and
      pathophysiologic effects, protein kinetics, such as production rate and
      fractional catabolic rate, can offer substantially more information than protein
      concentration alone. Kinetic experiments with stable isotope tracers typically
      require laborious sample preparation and are most often used for studying
      abundant proteins. Here we describe a practical methodology for measuring isotope
      enrichment into low-abundance proteins that uses an automated procedure and
      immunoaffinity enrichment (IA) with LC-MS. Low-abundance plasma proteins
      cholesteryl ester transfer protein (CETP) and proprotein convertase
      subtilisin/kexin type 9 (PCSK9) were studied as examples. METHODS: Human
      participants (n = 39) were infused with [(2)H(3)]leucine, and blood samples were
      collected at multiple time points. Sample preparation and analysis were automated
      and multiplexed to increase throughput. Proteins were concentrated from plasma by
      use of IA and digested with trypsin to yield proteotypic peptides that were
      analyzed by microflow chromatography-mass spectrometry to measure isotope
      enrichment. RESULTS: The IA procedure was optimized to provide the greatest
      signal intensity. Use of a gel-free method increased throughput while increasing
      the signal. The intra- and interassay CVs were <15% at all isotope enrichment
      levels studied. More than 1400 samples were analyzed in <3 weeks without the need
      for instrument stoppages or user interventions. CONCLUSIONS: The use of automated
      gel-free methods to multiplex the measurement of isotope enrichment was applied
      to the low-abundance proteins CETP and PCSK9.

PMID- 24751377
TI  - Effects of increased summer flooding on nitrogen dynamics in impounded mangroves.
AB  - Mangroves are important for coastal protection, carbon sequestration and habitat
      provision for plants and animals in the tropics and subtropics. Mangroves are
      threatened by habitat destruction and sea level rise, but management activities
      such as impounding for mosquito control can also have negative effects. We
      studied the effects of Rotational Impoundment Management (RIM) on nitrogen
      dynamics in impoundments dominated by three types of Black mangrove (Avicennia
      germinans) stands along the Indian River Lagoon (Florida). RIM, designed for
      noxious insect control, involves pumping estuarine water into impoundments in
      this area during spring and summer to raise water levels by 30 cm. We compared
      aspects of the nitrogen cycle before and after the start of the RIM and measured
      the same variables in an impoundment without RIM management. RIM led to the
      accumulation of ammonium in the substrate which coincided with a lowering of
      nitrification rates and decreased denitrification rates. Salt pan habitats
      dominated by dwarf mangroves became less saline following RIM initiation. Shoot
      growth of mangroves increased in response to higher nitrogen availability and
      lower pore water salinity. Mangrove responses were greatest in areas with dwarf
      and sparse mangrove cover. Overall, RIM resulted in lower nitrification and
      denitrification leading to lower nitrogen losses and increased Black mangrove
      growth, all benefits of RIM beyond those associated with noxious insect control. 

PMID- 24751378
TI  - The French adaptation of the Health of the Nation Outcome Scale for Children and
      Adolescents Self-Rated Form (F-HoNOSCA-SR): validation and clinical routine use.
AB  - The current study aimed to explore the validity of an adaptation into French of
      the self-rated form of the Health of the Nation Outcome Scales for Children and
      Adolescents (F-HoNOSCA-SR) and to test its usefulness in a clinical routine use.
      One hundred and twenty nine patients, admitted into two inpatient units, were
      asked to participate in the study. One hundred and seven patients filled out the
      F-HoNOSCA-SR (for a subsample (N=17): at two occasions, one week apart) and the
      strengths and difficulties questionnaire (SDQ). In addition, the clinician rated
      the clinician-rated form of the HoNOSCA (HoNOSCA-CR, N=82). The reliability
      (assessed with split-half coefficient, item response theory (IRT) models and
      intraclass correlations (ICC) between the two occasions) revealed that the F
      HoNSOCA-SR provides reliable measures. The concurrent validity assessed by
      correlating the F-HoNOSCA-SR and the SDQ revealed a good convergent validity of
      the instrument. The relationship analyses between the F-HoNOSCA-SR and the
      HoNOSCA-CR revealed weak but significant correlations. The comparison between the
      F-HoNOSCA-SR and the HoNOSCA-CR with paired sample t-tests revealed a higher
      score for the self-rated version. The F-HoNSOCA-SR was reported to provide
      reliable measures. In addition, it allows us to measure complementary information
      when used together with the HoNOSCA-CR. 

PMID- 24751379
TI  - The effect of language on functional capacity assessment in middle-aged and older
      US Latinos with schizophrenia.
AB  - The U.S. Latino population is steadily increasing, prompting a need for cross
      cultural outcome measures in schizophrenia research. This study examined the
      contribution of language to functional assessment in middle-aged Latino patients
      with schizophrenia by comparing 29 monolingual Spanish-speakers, 29 Latino
      English-speakers, and 29 non-Latino English-speakers who were matched on relevant
      demographic variables and who completed cognitive and functional assessments in
      their native language. There were no statistically significant differences
      between groups on the four everyday functioning variables (UCSD Performance-Based
      Skills Assessment [UPSA], Social Skills Performance Assessment [SSPA], Medication
      Management Ability Assessment [MMAA], and the Global Assessment of Functioning
      [GAF]). The results support the cross-linguistic and cross-cultural acceptability
      of these functional assessment instruments. It appears that demographic variables
      other than language (e.g., age, education) better explain differences in
      functional assessment among ethnically diverse subpopulations. Considering the
      influence of these other factors in addition to language on functional
      assessments will help ensure that measures can be appropriately interpreted among
      the diverse residents of the United States. 

PMID- 24751380
TI  - Shorter gaze duration for happy faces in current but not remitted depression:
      evidence from eye movements.
AB  - Cognitive theories of depression propose that depressed individuals
      preferentially attend to negative information and that such cognitive biases
      constitute important vulnerability and maintenance factors for the disorder. Most
      studies examined this bias by registration of response latencies. The present
      study employed a direct and continuous measurement of attentional processing for
      emotional stimuli by recording eye movements. Currently depressed (CD), remitted
      depressed (RD) and healthy control (HC) participants viewed slides presenting
      sad, angry, happy and neutral facial expressions. For each expression, four
      components of visual attention were analyzed: first fixation, maintained
      fixation, relative fixation frequency and glance duration. Results showed that
      healthy controls were characterized by longer gaze duration for happy faces
      compared to currently depressed individuals but not compared to remitted
      depressed individuals. Both patient groups (CD, RD) demonstrated longer
      maintained fixation (dwelling time) on all emotional faces compared to healthy
      controls. The present findings are in line with the presumption that depression
      is associated with a loss of elaborative processing of positive stimuli that
      characterizes healthy controls. Importantly, successful remission of depression
      (RD group) may result in positive attentional processing as no group differences
      were found between healthy controls and remitted patients on glance duration for
      happy faces. 

PMID- 24751381
TI  - Biotechnological production of muconic acid: current status and future prospects.
AB  - Muconic acid (MA), a high value-added bio-product with reactive dicarboxylic
      groups and conjugated double bonds, has garnered increasing interest owing to its
      potential applications in the manufacture of new functional resins, bio-plastics,
      food additives, agrochemicals, and pharmaceuticals. At the very least, MA can be
      used to produce commercially important bulk chemicals such as adipic acid,
      terephthalic acid and trimellitic acid. Recently, great progress has been made in
      the development of biotechnological routes for MA production. This present review
      provides a comprehensive and systematic overview of recent advances and
      challenges in biotechnological production of MA. Various biological methods are
      summarized and compared, and their constraints and possible solutions are also
      described. Finally, the future prospects are discussed with respect to the
      current state, challenges, and trends in this field, and the guidelines to
      develop high-performance microbial cell factories are also proposed for the MA
      production by systems metabolic engineering. 

PMID- 24751382
TI  - Recovery of carboxylic acids produced by fermentation.
AB  - Carboxylic acids such as citric, lactic, succinic and itaconic acids are useful
      products and are obtained on large scale by fermentation. This review describes
      the options for recovering these and other fermentative carboxylic acids. After
      cell removal, often a primary recovery step is performed, using liquid-liquid
      extraction, adsorption, precipitation or conventional electrodialysis. If the
      carboxylate is formed rather than the carboxylic acid, the recovery process
      involves a step for removing the cation of the formed carboxylate. Then, bipolar
      electrodialysis and thermal methods for salt splitting can prevent that waste
      inorganic salts are co-produced. Final carboxylic acid purification requires
      either distillation or crystallization, usually involving evaporation of water.
      Process steps can often be combined synergistically. In-situ removal of
      carboxylic acid by extraction during fermentation is the most popular approach.
      Recovery of the extractant can easily lead to waste inorganic salt formation,
      which counteracts the advantage of the in-situ removal. For industrial
      production, various recovery principles and configurations are used, because the
      fermentation conditions and physical properties of specific carboxylic acids
      differ. 

PMID- 24751383
TI  - Heat shock induces expression of OSTC/DC2, a novel subunit of
      oligosaccharyltransferase, in vitro and in vivo.
AB  - Mammalian oligosaccharyltransferase complex subunit OSTC/DC2 protein has recently
      been shown to be a new subunit of the oligosaccharyltransferase; however, its
      physiological role is still unclear. Here, we report the expression pattern of
      OSTC/DC2 protein in the context of heat shock stress. Its upregulation was
      detected both in cells treated with heat shock in vitro and in an animal model of
      heat shock in vivo. Northern blot analysis indicated that OSTC/DC2 mRNA is
      ubiquitously expressed in various human tissues, with abundant expression in the
      placenta and liver. The temporal changes of OSTC/DC2 protein expression following
      acute heat shock in human malignant glioblastoma cell line U87MG and mice were
      analyzed by Western blot assay. In general, expression of OSTC/DC2 protein was
      elevated after heat shock; however, the time courses of the change of OSTC/DC2
      protein expression varied in different tissues. In the cerebellum, heat shock
      induction of OSTC/DC2 protein and activation of AKT, a key regulator of stress
      response, followed a similar time course. These results suggest that the
      upregulation of OSTC/DC2, a novel component of the oligosaccharyltransferase
      complex, is part of the mammalian heat shock response. 

PMID- 24751384
TI  - Expression of chemokine receptor-4 in bone marrow mesenchymal stem cells on
      experimental rat abdominal aortic aneurysms and the migration of bone marrow
      mesenchymal stem cells with stromal-derived factor-1.
AB  - This study investigated the expression and role of chemokine receptor-4 (CXCR4)
      in bone marrow mesenchymal stem cells (BMSCs) from experimental rats with
      abdominal aortic aneurysms (AAA) for migration of BMSCs. Sprague-Dawley rats were
      divided into an experimental group and control group (n = 18 each). AAA was
      induced with 0.75 M solution infiltrate for 30 minutes, after which the abdomen
      was rinsed and closed. Saline was used in place of CaCl2 in the control group.
      CD34 and CD29 were detected by flow cytometry, the gene and protein expression of
      CXCR4 were detected by real-time polymerase chain reaction and western blot,
      respectively. The migration of BMSCs with stromal-derived factor-1 was detected
      by Transwell chamber. CD34 expression was negative and CD29 expression was
      positive. The gene and protein expression of CXCR4 were significantly higher in
      experimental group than them in control group (p < 0.05), the migration ability
      of BMSCs from the experimental group was significantly higher than that from the
      control group (p < 0.05). Stromal-derived factor -1/CXCR4 can enhance the
      migration of BMSCs in vitro in a rat AAA model. 

PMID- 24751385
TI  - Survival of motor neuron protein downregulates miR-9 expression in patients with
      spinal muscular atrophy.
AB  - Spinal muscular atrophy (SMA) is a lethal hereditary disease caused by homozygous
      absence of the survival of the motor neuron (SMN) 1 gene (SMN1), and it is the
      leading genetic cause of infant mortality. The severity of SMA is directly
      correlated with SMN protein levels in affected patients; however, the cellular
      regulatory mechanisms for SMN protein expression are not completely understood.
      In this study, we investigated the regulatory effects between SMN expression and
      miR-9a, a downstream noncoding small RNA. Using an inducible SMN short hairpin
      RNA interference (shRNAi) system in NSC 34 and human skin fibroblast cells,
      cellular miR-9 levels and SMN protein repression were time-dependently
      upregulated. Conversely, cellular miR-9 levels decreased when HeLa cells were
      transfected with SMN protein fused with green fluorescent protein. In SMA-like
      mice spinal cords and human primary skin fibroblasts isolated from patients with
      different degrees of SMA, human SMN exhibited a disease severity-dependent
      decrease, whereas cellular miR-9 levels increased. These results clearly
      suggested that cellular SMN proteins regulated miR-9 expression and that miR-9
      expression was related to SMA severity. Thus, miR-9 may be a marker for SMA
      prognosis. 

PMID- 24751386
TI  - Relationship between metalloproteinase 2 and 9 concentrations and soluble CD154
      expression in Iranian patients with multiple sclerosis.
AB  - Matrix metalloproteinases (MMPs) play a critical role in the blood-brain barrier
      permeability and in invasion of the leukocytes into the central nervous system
      during multiple sclerosis (MS). In this respect, in the present study, we have
      evaluated the possible role of MMP-9 and MMP-2 on the expression of soluble CD154
      (sCD154) and membrane-bound isoform of the CD154 in Iranian MS patients. The
      expressions of the aforementioned protein-related genes were analyzed at the
      levels of messenger RNA and proteins by real-time reverse transcription
      polymerase chain reaction, enzyme-linked immunosorbent assay, and Western
      blotting. The results showed a high expression of CD154 isoforms, MMP-9 and MMP
      2, in MS patients in contrast to controls (p < 0.001). We found an increase in
      sCD154 concentration (i.e., >3-fold) in patients with a higher MMPs/tissue
      inhibitor of metalloproteinase 1 (TIMP-1) ratio. Furthermore, secondary
      progressive MS patients with exacerbate period showed higher positive correlation
      between increasing sCD154 concentration and overexpression of MMP-2 (p < 0.001).
      Our data demonstrate that following the exacerbation period, sCD154 concentration
      is increased in patients, which is mutually related to the MMPs/TIMP-1 ratio.
      This relationship may represent a new link between sCD154 concentration and the
      MMPs/TIMP-1 ratio with prognostic implications. 

PMID- 24751387
TI  - Ureteroscope-assisted double-J stenting following laparoscopic ureterolithotomy.
AB  - The aim of this study was to examine the feasibility of ureteroscope-assisted
      double-J stenting following laparoscopic ureterolithotomy and to evaluate the
      effects of retrograde ureteroscopic access exerted on the sutured ureterotomy
      site. From January 2002 to December 2011, 30 patients with proximal ureteral
      stone underwent ureteroscopic double-J stenting of the ureter following
      retroperitoneal laparoscopic ureterolithotomy. Patient demographics and
      perioperative parameters, including the degree of hydronephrosis, urine leakage,
      and drainage time, were retrospectively reviewed. These data were compared with
      those of 30 consecutive patients who received open ureterolithotomy and
      intracorporeal ureteral double-J stenting. In addition, a PubMed search was
      conducted and the related literature on the placement of a ureteral stent was
      reviewed. Twenty-eight patients successfully underwent ureteral double-J stenting
      with ureteroscopic access. No malposition of the ureteral stent was identified in
      the ureteroscopic group, but two patients in the intracorporeal group required
      postoperative adjustment of the stent. Residual stone fragments were found during
      stent placement in three patients in the ureteroscopic group and holmium:yttrium
      aluminum-garnet laser lithotripsy was immediately performed. There was no
      significant difference in postoperative outcomes or complication rates between
      the two groups. Ureteroscope-assisted ureteral double-J stenting is a simple and
      safe alternative allowing intraluminal navigation along the entire ureter,
      correct stent placement, and prompt treatment of residual stone fragments,
      without radiation exposure. In addition, ureteral disruption and urinary
      extravasation may not be concerns for ureteroscopic access with continuous normal
      saline irrigation. 

PMID- 24751388
TI  - Dose-dependent attenuation of intravenous nalbuphine on epidural morphine-induced
      pruritus and analgesia after cesarean delivery.
AB  - Epidural morphine in patient-controlled analgesia regimens controls postoperative
      pain well but easily induces pruritus and other epidural morphine-related side
      effects. With 90 pregnant American Society of Anesthesiologists physical status
      II females scheduled for elective cesarean delivery, the present study was
      designed to evaluate the efficacy and safety profile of patient-controlled
      antipruritus (PCP) use of intravenous nalbuphine-based regimens for attenuation
      of postoperative pruritus and related side effects in combination with epidural
      morphine patient-controlled analgesia with regard to the quality of postoperative
      pain management. Patients were randomly assigned to two nalbuphine groups (5
      MUg/kg/hour, Group N5 or 10 MUg/kg/hour, Group N10) and bolus dose of 1.6 MUg/kg
      for PCP or the control (normal saline) group. Comparable visual analog scale
      scores for rest pain at each measured time interval among the three groups
      demonstrated that adequate pain relief was offered; however, the cumulative dose
      of nalbuphine administered to the patients in Group N10 attenuated the analgesic
      effect of epidural morphine in moving pain at POh24 only. Fewer episodes and
      milder severity of pruritus were observed in patients in Groups N5 and N10 at all
      postoperative time intervals. Epidural morphine provided good postoperative pain
      relief but with incommodious side effects. In addition, intravenous nalbuphine
      not only attenuated the incidence of pruritus but also decreased total morphine
      consumption. In conclusion, intravenous administration of low-dose nalbuphine (5
      MUg/kg/hour) for PCP maintained analgesia produced by epidural morphine and
      offered low pruritus incidence. 

PMID- 24751389
TI  - Clinicopathological analysis and survival outcome of duodenal adenocarcinoma.
AB  - Duodenal adenocarcinoma is a rare cancer, contributing <10 % of periampullary
      carcinoma. This study reviews the single center experience of duodenal
      adenocarcinoma and analyzes the clinical and pathological factors to predict
      survival and recurrence. The records of 50 patients with duodenal adenocarcinoma
      who underwent surgical exploration or resection from 1995 to 2010 were reviewed
      retrospectively. Univariate and multivariate analyses were performed to identify
      the clinicopathological factors associated with survival and recurrence. There
      were 35 men and 15 women, with a mean age of 61 years. In multivariate analysis
      of 50 patients, R0 resection [p = 0.041, hazard ratio (HR) = 3.569, 95%
      confidence interval (CI) = 1.057-12.054] and symptom at initial admission (p =
      0.025, HR = 11.210, 95% CI = 1.354-92.812) were independent prognostic factors
      for overall survival. Thirty-six patients underwent curative resection
      (resectability 72%). The 5-year survival rates for curative and noncurative
      resections were 46.4% and 0%, respectively. Univariate analysis of 36 patients
      who underwent R0 resection revealed that symptoms at initial admission (p =
      0.023), presence of lymph node metastasis (p = 0.034), and perineural invasion (p
      = 0.025) were significant prognostic factors after curative resection. There was
      no significant factor for overall survival in the multivariate analysis. There
      was recurrence in 15 patients, mainly as liver metastasis. Multivariate analysis
      revealed that presence of symptom (p = 0.047, HR = 5.362, 95% CI = 1.021-28.149)
      and ulcerative tumor (p = 0.036, HR = 5.668, 95% CI = 1.123-28.619) were
      independent factors for disease free survival. An aggressive surgical approach to
      achieve R0 resection was important to enhance survival. Most of the recurrence
      occurred within 1 year after surgery. Close follow-up is necessary after surgical
      resection. 

PMID- 24751390
TI  - Meningioma-induced Cushing's syndrome due to ectopic production of corticotropin
      releasing hormone: a case study of clinical presentation.

PMID- 24751391
TI  - Approach to cases with multiple invagination.

PMID- 24751392
TI  - Ramsay Hunt syndrome with vocal fold paralysis.

PMID- 24751393
TI  - Predictors of myocardial recovery in pediatric tachycardia-induced
      cardiomyopathy.
AB  - BACKGROUND: Tachycardia-induced cardiomyopathy (TIC) carries significant risk of
      morbidity and mortality, although full recovery is possible. Little is known
      about the myocardial recovery pattern. OBJECTIVE: The purpose of this study was
      to determine the time course and predictors of myocardial recovery in pediatric
      TIC. METHODS: An international multicenter study of pediatric TIC was conducted.
      Children <=18 years with incessant tachyarrhythmia, cardiac dysfunction (left
      ventricular ejection fraction [LVEF] <50%), and left ventricular (LV) dilation
      (left ventricular end-diastolic dimension [LVEDD] z-score >=2) were included.
      Children with congenital heart disease or suspected primary cardiomyopathy were
      excluded. Primary end-points were time to LV systolic functional recovery (LVEF
      >=55%) and normal LV size (LVEDD z-score <2). RESULTS: Eighty-one children from
      17 centers met inclusion criteria: median age 4.0 years (range 0.0-17.5 years)
      and baseline LVEF 28% (interquartile range 19-39). The most common arrhythmias
      were ectopic atrial tachycardia (59%), permanent junctional reciprocating
      tachycardia (23%), and ventricular tachycardia (7%). Thirteen required
      extracorporeal membrane oxygenation (n = 11) or ventricular assist device (n = 2)
      support. Median time to recovery was 51 days for LVEF and 71 days for LVEDD. Two
      (4%) underwent heart transplantation, and 1 died (1%). Multivariate predictors of
      LV systolic functional recovery were age (hazard ratio [HR] 0.61, P = .040),
      standardized tachycardia rate (HR 1.16, P = .015), mechanical circulatory support
      (HR 2.61, P = .044), and LVEF (HR 1.33 per 10% increase, p=0.005). For
      normalization of LV size, only baseline LVEDD (HR 0.86, P = .008) was predictive.
      CONCLUSION: Pediatric TIC resolves in a predictable fashion. Factors associated
      with faster recovery include younger age, higher presenting heart rate, use of
      mechanical circulatory support, and higher LVEF, whereas only smaller baseline LV
      size predicts reverse remodeling. This knowledge may be useful for clinical
      evaluation and follow-up of affected children.

PMID- 24751395
TI  - The brain in flux: genetic, physiologic, and therapeutic perspectives on
      transporters in the CNS.

PMID- 24751394
TI  - Flow cytometric analysis of red blood cell osmotic fragility.
AB  - This study investigated a new method of flow cytometry (FCM) for analysis of red
      blood cell (RBC) osmotic fragility. Venous peripheral blood collected in a
      sampling tube coated with EDTA 2Na was analyzed using FCM to determine RBC
      osmotic fragility. RBCs were represented as a double-peaked forward scatter (FSC)
      histogram in FCM. RBCs showed ballooning and spherical shape change in hypotonic
      solutions before hemolysis. The ballooning of RBCs was expressed as a
      disappearance of the minor peak and by narrowing and a shift to the right of the
      FSC histogram. The process of hemolysis was expressed as shrinking of the RBC
      cytogram in the right upper quadrant on the scatter plot of side scatter versus
      FSC and by emergence of a cell debris cytogram in the left lower quadrant. The
      ratio of intact RBCs in hypotonic solution was available as an indicator of
      osmotic fragility. Acidic solution made erythrocytes less tolerant to hypotonic
      solution by inducing spherical shape change. In conclusion, FCM can be used to
      assess RBC osmotic fragility. 

PMID- 24751396
TI  - Serologic evidence of influenza A(H1N1)pdm09 virus infection in northern sea
      otters.

PMID- 24751397
TI  - Increased hepatic CD36 expression with age is associated with enhanced
      susceptibility to nonalcoholic fatty liver disease.
AB  - CD36 has been associated with obesity and diabetes in human liver diseases,
      however, its role in age-associated nonalcoholic fatty liver disease (NAFLD) is
      unknown. Therefore, liver biopsies were collected from individuals with
      histologically normal livers (n=30), and from patients diagnosed with simple
      steatosis (NAS; n=26). Patients were divided into two groups according to age and
      liver biopsy samples were immunostained for CD36. NAFLD parameters were examined
      in young (12-week) and middle-aged (52-week) C57BL/6J mice, some fed with chow
      diet and some fed with low-fat (LFD; 10% kcal fat) or high-fat diet (HFD; 60%
      kcal fat) for 12-weeks. CD36 expression was positively associated with age in
      individuals with normal livers but not in NAS patients. However, CD36 was
      predominantly located at the plasma membrane of hepatocytes in aged NAS patients
      as compared to young. In chow-fed mice, aging, despite an increase in hepatic
      CD36 expression, was not associated with the development of NAFLD. However,
      middle-aged mice did exhibit the development of HFD-induced NAFLD, mediated by an
      increase of CD36 on the membrane. Enhanced CD36-mediated hepatic fat uptake may
      contribute to an accelerated progression of NAFLD in mice and humans. Therapies
      to prevent the increase in CD36 expression and/or CD36 from anchoring at the
      membrane may prevent the development of NAFLD. 

PMID- 24751398
TI  - The constitutive expression of a two transgene construct enhances the abiotic
      stress tolerance of chrysanthemum.
AB  - Various abiotic stresses downgrade the quality and productivity of chrysanthemum.
      A construct carrying both CcSOS1 (from Chrysanthemum crassum) and CdICE1 (from
      Chrysanthemum dichrum) was constitutively expressed in the chrysanthemum variety
      'Jinba'. The transgenic plants were superior to the wild type (WT) ones with
      respect to their sensitivity to low temperature, drought and salinity, as
      measured by visible damage and plant survival. Salinity stressed transgenic
      plants accumulated more proline, and their level of superoxide dismutase and
      peroxidase activity was higher than in WT plants. At the physiological level,
      they suffered less loss of viable leaf area, maintained a lower leaf electrolyte
      conductivity and retained more chlorophyll (a+b). The ratio between the K(+) and
      Na(+) content was higher in the root, stem and median leaves of salinity stressed
      transgenic plants than in those of WT plants.

PMID- 24751399
TI  - Identification and characterization of the 14-3-3 gene family in Hevea
      brasiliensis.
AB  - The 14-3-3 proteins are a family of conserved phospho-specific binding proteins
      involved in diverse physiological processes. Although the genome-wide analysis of
      this family has been carried out in certain plant species, little is known about
      14-3-3 protein genes in rubber tree (Hevea brasiliensis). In this study, we
      identified 10 14-3-3 protein genes (designated as HbGF14a to HbGF14j) in the
      latest rubber tree genome. A phylogenetic tree was constructed and found to
      demonstrate that HbGF14s can be divided into two major groups. Tissue-specific
      expression profiles showed that 10 HbGF14 were expressed in at least one of the
      tissues, which suggested that HbGF14s participated in numerous cellular
      processes. The 10 HbGF14s responded to jasmonic acid (JA) and ethylene (ET)
      treatment, which suggested that these HbGF14s were involved in response to JA and
      ET signaling. The target of HbGF14c protein was related to small rubber particle
      protein, a major rubber particle protein that is involved in rubber biosynthesis.
      These findings suggested that 14-3-3 proteins may be involved in the regulation
      of natural rubber biosynthesis.

PMID- 24751400
TI  - Cerium dioxide and zinc oxide nanoparticles alter the nutritional value of soil
      cultivated soybean plants.
AB  - The aim of this study was to determine nutrient elements in soybean (Glycine max)
      plants cultivated in farm soil amended with nCeO2 at 0-1000 mg kg(-1) and nZnO at
      0-500 mg kg(-1). Digested samples were analyzed by ICP-OES/MS. Compared to
      control, pods from nCeO2 at 1000 mg kg(-1) had significantly less Ca but more P
      and Cu, while pods from 100 mg kg(-1)nZnO had more Zn, Mn, and Cu. Plants treated
      with nZnO showed significant correlations among Zn, P, and S in pods with Zn in
      roots. Correlations among pod Zn/root Zn was r = 0.808 (p <= 0.01) and pod P/root
      P was r = 0.541 (p <= 0.05). The correlation among pod S/root S was r = -0.65 (p
      <= 0.01). While nCeO2 treatments exhibited significant correlations between pod
      Ca/root Ca (r = 0.645, p <= 0.05). The data suggest that nCeO2 and nZnO alter the
      nutritional value of soybean, which could affect the health of plants, humans,
      and animals.

PMID- 24751401
TI  - Comparison of risk for early-onset sepsis in small-for-gestational-age neonates
      and appropriate-for-gestational-age neonates based on lower levels of white blood
      cell, neutrophil, and platelet counts.

PMID- 24751402
TI  - The CHA2DS2-VASc score as a predictor of left atrial thrombus in patients with
      non-valvular atrial fibrillation.
AB  - OBJECTIVE: To investigate whether or not the CHA2DS2-VASc score predicts left
      atrial (LA) thrombus detected on pre-cardioversion transoesophageal
      echocardiography (TEE). MATERIALS AND METHODS: The medical records of patients
      who had undergone TEE were reviewed to assess the presence of LA thrombus prior
      to direct-current cardioversion for atrial fibrillation (AF). The CHA2DS2-VASc
      score was calculated for each patient. Clinical TEE reports were reviewed for the
      presence of LA thrombus. Patients with a valve prosthesis or rheumatic mitral
      valve disease were excluded from this study. RESULTS: A total of 309 patients
      were identified. The mean age was 70.1 +/- 9.8 years and 151 (49%) patients were
      males and 158 (51%) were females. LA thrombus was seen in 32 (10.3%) of the 309
      patients. Fifty (16.2%) patients had a low CHA2DS2-VASc score (0-1), 230 (74.4%)
      had an intermediate score (2-4) and 29 (9.4%) had a high score (5-9). The
      incidence of LA thrombus in the low, intermediate and high CHA2DS2-VASc score
      groups was 0, 4.4 and 68.7%, respectively. The LA thrombus risk increased with
      increasing CHA2DS2-VASc scores. On multivariate logistic analysis, the CHA2DS2
      VASc score (OR 3.26, 95% CI 2.3-4.65; p = 0.001) and age (OR 0.93, 95% CI 0.88
      0.98; p = 0.004) were independent risk factors for LA thrombus in patients with
      non-valvular AF. CONCLUSION: A high CHA2DS2-VASc score was independently
      associated with the presence of LA thrombus in patients with non-valvular AF.

PMID- 24751404
TI  - Does increasing the pulse duration increase the efficacy of long pulsed Nd:YAG
      laser assisted hair removal? A split-chin clinical trial.

PMID- 24751403
TI  - Microarray expression profile analysis of long non-coding RNAs in human gastric
      cardiac adenocarcinoma.
AB  - BACKGROUND/AIMS: Long noncoding RNAs (lncRNAs) are pervasively transcribed and
      have been shown to regulate key biological processes that maintain normal
      cellular functions. Abnormal regulation of these lncRNAs can promote
      tumorigenesis through resulting aberrant cellular essential functions. however,
      the roles of lncRNAs played in the development of gastric cardiac adenocarcinoma
      (GCA) remain unknown. With this work we aimed to show the expression profile of
      lncRNAs in GCA tissues compared with paired adjacent noncancerous tissue using
      microarray analysis in order to interrogate potential carcinogenesis molecular
      mechanisms of GCA from lncRNA level. METHODS: In this study, total RNA was
      isolated from 15 pairs of GCA tissue, cancerous and non-cancerous, and hybridized
      to arraystar lncRNA V2.0 chips containing probes representing 33,000 lncRNA
      genes. Quantitative real-time polymerase chain reaction (PCR) was used to
      validate 6 up-regulated and 6 down-regulated lncRNAs. Bioinformatic analysis
      including gene ontology(GO) analysis, pathway analysis and network analysis was
      done for further investigation. RESULTS: Pathway analysis indicated that 8
      pathways corresponded to downregulated transcripts and that 20 pathways
      corresponded to up-regulated transcripts (p-value cut-off is 0.05). GO analysis
      showed that the highest enriched GOs targeted by up-regulated transcripts were
      tissue homeostasis and the highest esenriched GOs targeted by the downregulated
      transcripts were tissue homeostasis. CONCLUSION: Our study is the first to
      interrogate differentially expressed lncRNAs in human GCA tissues and indicates
      that lncRNAs may be used as novel candidate biomarkers for the clinical diagnosis
      of GCA and potential targets for further therapy.

PMID- 24751405
TI  - Cortical responses to optic flow and motion contrast across patterns and speeds.
AB  - Motion provides animals with fast and robust cues for navigation and object
      detection. In the first case, stereotyped patterns of optic flow inform a moving
      observer about the direction and speed of its own movement. In the case of object
      detection, regional differences in motion allow for the segmentation of figures
      from their background, even in the absence of color or shading cues. Previous
      research has investigated human electrophysiological responses to global motion
      across speeds, but only focused upon one type of optic flow pattern. Here, we
      compared steady-state visual evoked potential (SSVEP) responses across patterns
      and speeds, both for optic flow and for motion-defined figure patterns, to assess
      the extent to which the processes are pattern-general or pattern-specific. For
      optic flow, pattern and speed effects on response amplitudes varied substantially
      across channels, suggesting pattern-specific processing at slow speeds and
      pattern-general activity at fast speeds. Responses for coherence- and direction
      defined figures were comparatively more uniform, with similar response profiles
      and spatial distributions. Self- and object-motion patterns activate some of the
      same circuits, but these data suggest differential sensitivity: not only across
      the two classes of motion, but also across the patterns within each class, and
      across speeds. Thus, the results demonstrate that cortical processing of global
      motion is complex and activates a distributed network. 

PMID- 24751406
TI  - Prospective evaluation of dual-energy imaging in patients undergoing image guided
      radiation therapy for lung cancer: initial clinical results.
AB  - PURPOSE: A prospective feasibility study was conducted to investigate the utility
      of dual-energy (DE) imaging compared to conventional x-ray imaging for patients
      undergoing kV-based image guided radiation therapy (IGRT) for lung cancer.
      METHODS AND MATERIALS: An institutional review board-approved feasibility study
      enrolled patients with lung cancer undergoing IGRT and was initiated in September
      2011. During daily setup, 2 sequential respiration-gated x-ray images were
      obtained using an on-board imager. Imaging was composed of 1 standard x-ray image
      at 120 kVp (1 mAs) and a second image obtained at 60 kVp (4 mAs). Weighted
      logarithmic subtraction of the 2 images was performed offline to create a soft
      tissue-selective DE image. Conventional and DE images were evaluated by measuring
      relative contrast and contrast-to-noise ratios (CNR) and also by comparing
      spatial localization, using both approaches. Imaging dose was assessed using a
      calibrated ion chamber. RESULTS: To date, 10 patients with stage IA to IIIA lung
      cancer were enrolled and 57 DE images were analyzed. DE subtraction resulted in
      complete suppression of overlying bone in all 57 DE images, with an average
      improvement in relative contrast of 4.7 +/- 3.3 over that of 120 kVp x-ray images
      (P<.0002). The improvement in relative contrast with DE imaging was seen for both
      smaller (gross tumor volume [GTV] <=5 cc) and larger tumors (GTV >5 cc), with
      average relative contrast improvement ratios of 3.4 +/- 4.1 and 5.4 +/- 3.6,
      respectively. Moreover, the GTV was reliably localized in 95% of the DE images
      versus 74% of the single energy (SE images, (P=.004). Mean skin dose per DE image
      set was 0.44 +/- 0.03 mGy versus 0.43 +/- 0.03 mGy, using conventional kV imaging
      parameters. CONCLUSIONS: Initial results of this feasibility study suggest that
      DE thoracic imaging may enhance tumor localization in lung cancer patients
      receiving kV-based IGRT without increasing imaging dose.

PMID- 24751407
TI  - Dose-escalation study for cardiac radiosurgery in a porcine model.
AB  - PURPOSE: To perform a proof-of-principle dose-escalation study to radiosurgically
      induce scarring in cardiac muscle tissue to block veno-atrial electrical
      connections at the pulmonary vein antrum, similar to catheter ablation. METHODS
      AND MATERIALS: Nine mini-pigs underwent pretreatment magnetic resonance imaging
      (MRI) evaluation of heart function and electrophysiology assessment by catheter
      measurements in the right superior pulmonary vein (RSPV). Immediately after
      examination, radiosurgery with randomized single-fraction doses of 0 and 17.5-35
      Gy in 2.5-Gy steps were delivered to the RSPV antrum (target volume 5-8 cm(3)).
      MRI and electrophysiology were repeated 6 months after therapy, followed by
      histopathologic examination. RESULTS: Transmural scarring of cardiac muscle
      tissue was noted with doses >=32.5 Gy. However, complete circumferential scarring
      of the RSPV was not achieved. Logistic regressions showed that extent and
      intensity of fibrosis significantly increased with dose. The 50% effective dose
      for intense fibrosis was 31.3 Gy (odds ratio 2.47/Gy, P<.01). Heart function was
      not affected, as verified by MRI and electrocardiogram evaluation. Adjacent
      critical structures were not damaged, as verified by pathology, demonstrating the
      short-term safety of small-volume cardiac radiosurgery with doses up to 35 Gy.
      CONCLUSIONS: Radiosurgery with doses >32.5 Gy in the healthy pig heart can induce
      circumscribed scars at the RSPV antrum noninvasively, mimicking the effect of
      catheter ablation. In our study we established a significant dose-response
      relationship for cardiac radiosurgery. The long-term effects and toxicity of such
      high radiation doses need further investigation in the pursuit of cardiac
      radiosurgery for noninvasive treatment of atrial fibrillation.

PMID- 24751408
TI  - Clinical evaluation of normalized metal artifact reduction in kVCT using MVCT
      prior images (MVCT-NMAR) for radiation therapy treatment planning.
AB  - PURPOSE: To evaluate the metal artifacts in diagnostic kilovoltage computed
      tomography (kVCT) images of patients that are corrected by use of a normalized
      metal artifact reduction (NMAR) method with megavoltage CT (MVCT) prior images:
      MVCT-NMAR. METHODS AND MATERIALS: MVCT-NMAR was applied to images from 5
      patients: 3 with dual hip prostheses, 1 with a single hip prosthesis, and 1 with
      dental fillings. The corrected images were evaluated for visualization of tissue
      structures and their interfaces and for radiation therapy dose calculations. They
      were compared against the corresponding images corrected by the commercial
      orthopedic metal artifact reduction algorithm in a Phillips CT scanner. RESULTS:
      The use of MVCT images for correcting kVCT images in the MVCT-NMAR technique
      greatly reduces metal artifacts, avoids secondary artifacts, and makes patient
      images more useful for correct dose calculation in radiation therapy. These
      improvements are significant, provided the MVCT and kVCT images are correctly
      registered. The remaining and the secondary artifacts (soft tissue blurring,
      eroded bones, false bones or air pockets, CT number cupping within the metal)
      present in orthopedic metal artifact reduction corrected images are removed in
      the MVCT-NMAR corrected images. A large dose reduction was possible outside the
      planning target volume (eg, 59.2 Gy to 52.5 Gy in pubic bone) when these MVCT
      NMAR corrected images were used in TomoTherapy treatment plans without
      directional blocks for a prostate cancer patient. CONCLUSIONS: The use of MVCT
      NMAR corrected images in radiation therapy treatment planning could improve the
      treatment plan quality for patients with metallic implants.

PMID- 24751409
TI  - Stereotactic radiation therapy for benign meningioma: long-term outcome in 318
      patients.
AB  - PURPOSE: To investigate the long-term outcome of stereotactic-based radiation
      therapy in a large cohort of patients with benign intracranial meningiomas.
      METHODS AND MATERIALS: Between 1997 and 2010, 318 patients with histologically
      confirmed (44.7%; previous surgery) or imaging-defined (55.3%) benign meningiomas
      were treated with either fractionated stereotactic radiation therapy (79.6%),
      hypofractionated stereotactic radiation therapy (15.4%), or stereotactic
      radiosurgery (5.0%), depending on tumor size and location. Local control (LC),
      overall survival (OS), cause-specific survival (CSS), prognostic factors, and
      toxicity were analyzed. RESULTS: The median follow-up was 50 months (range, 12
      167 months). Local control, OS, and CSS at 5 years were 92.9%, 88.7%, and 97.2%,
      and at 10 years they were 87.5%, 74.1%, and 97.2%, respectively. In the
      multivariate analysis, tumor location (P=.029) and age >66 years (P=.031) were
      predictors of LC and OS, respectively. Worsening of pre-existing neurologic
      symptoms immediately after radiation therapy occurred in up to 2%. Clinically
      significant acute toxicity (grade 3 degrees ) occurred in 3%. Only grade 1-2 late
      toxicity was observed in 12%, whereas no new neurologic deficits or treatment
      related mortality were encountered. CONCLUSIONS: Patients with benign meningiomas
      predominantly treated with standard fractionated stereotactic radiation therapy
      with narrow margins enjoy excellent LC and CSS, with minimal long-term morbidity.

PMID- 24751411
TI  - Radiation therapy infrastructure and human resources in low- and middle-income
      countries: present status and projections for 2020.
AB  - PURPOSE: Radiation therapy, a key component of cancer management, is required in
      more than half of new cancer patients, particularly in low- and middle-income
      countries (LMICs). The projected rise in cancer incidence over the next decades
      in LMICs will result in an increasing demand for radiation therapy services.
      Considering the present cancer incidence and that projected for 2020 (as listed
      in GLOBOCAN), we evaluated the current and anticipated needs for radiation
      therapy infrastructure and staffing by 2020 for each of the LMICs. METHODS AND
      MATERIALS: Based on World Bank classification, 139 countries fall in the category
      of LMICs. Details of teletherapy, radiation oncologists, medical physicists, and
      radiation therapy technologists were available for 84 LMICs from the
      International Atomic Energy Agency-Directory of Radiotherapy Centres (IAEA-DIRAC)
      database. Present requirements and those for 2020 were estimated according to
      recommendations from the IAEA and European Society for Radiotherapy & Oncology
      (ESTRO-QUARTS). RESULTS: Only 4 of the 139 LMICs have the requisite number of
      teletherapy units, and 55 (39.5%) have no radiation therapy facilities at
      present. Patient access to radiation therapy in the remaining 80 LMICs ranges
      from 2.3% to 98.8% (median: 36.7%). By 2020, these 84 LMICs would additionally
      need 9169 teletherapy units, 12,149 radiation oncologists, 9915 medical
      physicists, and 29,140 radiation therapy technologists. Moreover, de novo
      radiation therapy facilities would have to be considered for those with no
      services. CONCLUSIONS: Twelve pragmatic steps are proposed for consideration at
      national and international levels to narrow the gap in radiation therapy access.
      Multipronged and coordinated action from all national and international
      stakeholders is required to develop realistic strategies to curb this impending
      global crisis.

PMID- 24751410
TI  - Baseline metabolic tumor volume and total lesion glycolysis are associated with
      survival outcomes in patients with locally advanced pancreatic cancer receiving
      stereotactic body radiation therapy.
AB  - PURPOSE: Although previous studies have demonstrated the prognostic value of
      positron emission tomography (PET) parameters in other malignancies, the role of
      PET in pancreatic cancer has yet to be well established. We analyzed the
      prognostic utility of PET for patients with locally advanced pancreatic cancer
      (LAPC) undergoing fractionated stereotactic body radiation therapy (SBRT).
      MATERIALS AND METHODS: Thirty-two patients with LAPC in a prospective clinical
      trial received up to 3 doses of gemcitabine, followed by 33 Gy in 5 fractions of
      6.6 Gy, using SBRT. All patients received a baseline PET scan prior to SBRT (pre
      SBRT PET). Metabolic tumor volume (MTV), total lesion glycolysis (TLG), and
      maximum and peak standardized uptake values (SUVmax and SUVpeak) on pre-SBRT PET
      scans were calculated using custom-designed software. Disease was measured at a
      threshold based on the liver SUV, using the equation Livermean + [2 * Liversd].
      Median values of PET parameters were used as cutoffs when assessing their
      prognostic potential through Cox regression analyses. RESULTS: Of the 32
      patients, the majority were male (n=19, 59%), 65 years or older (n=21, 66%), and
      had tumors located in the pancreatic head (n=27, 84%). Twenty-seven patients
      (84%) received induction gemcitabine prior to SBRT. Median overall survival for
      the entire cohort was 18.8 months (95% confidence interval [CI], 15.7-22.0). An
      MTV of 26.8 cm(3) or greater (hazard ratio [HR] 4.46, 95% CI 1.64-5.88, P<.003)
      and TLG of 70.9 or greater (HR 3.08, 95% CI 1.18-8.02, P<.021) on pre-SBRT PET
      scan were associated with inferior overall survival on univariate analysis. Both
      pre-SBRT MTV (HR 5.13, 95% CI 1.19-22.21, P=.029) and TLG (HR 3.34, 95% CI 1.07
      10.48, P=.038) remained independently associated with overall survival in
      separate multivariate analyses. CONCLUSIONS: Pre-SBRT MTV and TLG are potential
      predictive factors for overall survival in patients with LAPC and may assist in
      tailoring therapy.

PMID- 24751412
TI  - Decision analysis of stereotactic radiation surgery versus stereotactic radiation
      surgery and whole-brain radiation therapy for 1 to 3 brain metastases.
AB  - PURPOSE: Although whole-brain radiation therapy (WBRT) is effective for
      controlling intracranial disease, it is also associated with neurocognitive side
      effects. It is unclear whether a theoretically improved quality of life after
      stereotactic radiation surgery (SRS) alone relative to that after SRS with
      adjuvant WBRT would justify the omission of WBRT, given the higher risk of
      intracranial failure. This study compares SRS alone with SRS and WBRT, to
      evaluate the theoretical benefits of intracranial tumor control with adjuvant
      WBRT against its possible side effects, using quality-adjusted life expectancy
      (QALE) as a primary endpoint. METHODS AND MATERIALS: A Markov decision analysis
      model was used to compare QALE in a cohort of patients with 1 to 3 brain
      metastases and Karnofsky performance status of at least 70. Patients were treated
      with SRS alone or with SRS immediately followed by WBRT. Patients treated with
      SRS alone underwent surveillance magnetic resonance imaging and received salvage
      WBRT if they developed intracranial relapse. All patients whose cancer relapsed
      after WBRT underwent simulation as dying of intracranial progression. Model
      parameters were estimated from published literature. RESULTS: Treatment with SRS
      yielded 6.2 quality-adjusted life months (QALMs). The addition of initial WBRT
      reduced QALE by 1.2 QALMs. On one-way sensitivity analysis, the model was
      sensitive only to a single parameter, the utility associated with the state of no
      evidence of disease after SRS alone. At values greater than 0.51, SRS alone was
      preferred. CONCLUSIONS: In general, SRS alone is suggested to have improved
      quality of life in patients with 1 to 3 brain metastases compared to SRS and
      immediate WBRT. Our results suggest that immediate treatment with WBRT after SRS
      can be reserved for patients who would have a poor performance status regardless
      of treatment. These findings are stable under a wide range of assumptions.

PMID- 24751413
TI  - Direction-modulated brachytherapy for high-dose-rate treatment of cervical
      cancer. I: theoretical design.
AB  - PURPOSE: To demonstrate that utilization of the direction-modulated brachytherapy
      (DMBT) concept can significantly improve treatment plan quality in the setting of
      high-dose-rate (HDR) brachytherapy for cervical cancer. METHODS AND MATERIALS:
      The new, MRI-compatible, tandem design has 6 peripheral holes of 1.3-mm diameter,
      grooved along a nonmagnetic tungsten-alloy rod (rho = 18.0 g/cm(3)), enclosed in
      Delrin tubing (polyoxymethylene, rho = 1.41 g/cm(3)), with a total thickness of
      6.4 mm. The Monte Carlo N-Particle code was used to calculate the anisotropic
      (192)Ir dose distributions. An in-house-developed inverse planning platform,
      geared with simulated annealing and constrained-gradient optimization algorithms,
      was used to replan 15 patient cases (total 75 plans) treated with a conventional
      tandem and ovoids (T&O) applicator. Prescription dose was 6 Gy. For replanning,
      we replaced the conventional tandem with that of the new DMBT tandem for
      optimization but left the ovoids in place and kept the dwell positions as
      originally planned. All DMBT plans were normalized to match the high-risk
      clinical target volume V100 coverage of the T&O plans. RESULTS: In general there
      were marked improvements in plan quality for the DMBT plans. On average, D2cc for
      the bladder, rectum, and sigmoid were reduced by 0.59 +/- 0.87 Gy (8.5% +/-
      28.7%), 0.48 +/- 0.55 Gy (21.1% +/- 27.2%), and 0.10 +/- 0.38 Gy (40.6% +/-
      214.9%) among the 75 plans, with best single-plan reductions of 3.20 Gy (40.8%),
      2.38 Gy (40.07%), and 1.26 Gy (27.5%), respectively. The high-risk clinical
      target volume D90 was similar, with 6.55 +/- 0.96 Gy and 6.59 +/- 1.06 Gy for T&O
      and DMBT, respectively. CONCLUSIONS: Application of the DMBT concept to cervical
      cancer allowed for improved organ at risk sparing while achieving similar target
      coverage on a sizeable patient population, as intended, by maximally utilizing
      the anatomic information contained in 3-dimensional imaging. A series of
      mechanical and clinical validations are to be followed.

PMID- 24751414
TI  - Design and evaluation of a tandemly arranged outer membrane protein U (OmpU)
      multi-epitope as a potential vaccine antigen against Vibrio mimicus in grass
      carps (Ctenopharyngodon idella).
AB  - Vibrio mimicus (V. mimicus) is an extracellular pathogen that causes ascites
      disease in aquatic animals. In our previous studies, the outer membrane protein U
      (OmpU) of V. mimicus has been proven to be a protective antigen, and several
      mimotopes of the protein were identified. Here, a tandemly arranged multi-epitope
      peptide (named 6EPIS) was designed with six mimotopes and heterologously
      expressed. Then, the immunoprotection efficacy of recombinant 6EPIS (r6EPIS) was
      evaluated in grass carps (Ctenopharyngodon idella) by determining relative
      percentage survival (RPS), specific immunoglobulin M (IgM) antibody titer, and
      transcriptional levels of immune-related genes of inoculated grass carps. Fish
      vaccinated with r6EPIS via intraperitoneal injection exhibited 85.71% RPS over
      the control, when challenged with V. mimicus. The enzyme-linked immunosorbent
      assay titer of specific IgM antibodies against r6EPIS reached 1:12,800 on Day 28
      post the primary immunization. After 28 days post immunization, the
      transcriptional level of total IgM mRNA was significantly higher in the r6EPIS
      vaccinated fish than in those vaccinated with recombinant OmpU, inactivated
      bacterin and rHis tag peptide (p<0.05). In addition, the transcription levels of
      interleukin-1beta and tumor necrosis factor-alpha genes in the spleen and head
      kidney of r6EPIS-vaccinated fish were significantly increased during the period
      of immunization and early phase of infection, while the transcription level of
      interleukin-10 gene was significantly increased from Day 3 to 7 post challenge,
      compared to the control level. These results show that r6EPIS was highly
      immunogenic and could elicit strong protective immune responses. It may be an
      attractive vaccine candidate against V. mimicus infection.

PMID- 24751416
TI  - Evaluation of the mosquitocidal effect of Birbira (Mellitia ferruginea) seed
      extract against Anopheles arabiensis (Diptera: Culicidae) from Ethiopia.
AB  - Mosquito control using insecticides has been the most successful intervention
      known to reduce malaria prevalence and/or incidence. However, over time success
      has been hampered due to the development of resistance by mosquitoes against
      chemical insecticides recommended for public health use. Development of effective
      botanical mosquitocidal compounds however can be potential alternatives tool in
      malaria vector control. Thus, the present study aimed at investigating the
      mosquitocidal effect of "Birbira" (Mellitia ferruginea) seed extract against the
      primary malaria vector, Anopheles arabiensis from Ethiopia. The mosquitocidal
      activity of M. ferruginea was assessed following WHO susceptibility test
      procedure. Methanol extract of M. ferruginea seeds was evaluated against third &
      fourth instar larvae, pupae and, non-blood fed 3-5 days old laboratory strains
      and field populations of A. arabiensis under laboratory condition. Mortality was
      then recorded after 24h exposure. The seed extract of M. ferruginea showed high
      mosquitocidal activity against larvae, pupae and adult stages of both the
      laboratory strain and field population of A. arabiensis. The LC50 values for
      larvae and pupae population from a laboratory strains was, respectively, 14.7 and
      41.33mg/L. While the LC50 values for the larvae and a pupa of the field
      population were, respectively, 30.88 and 74.54mg/L. In addition, the LC99 and
      LD99 values were also identified. The findings of this study indicated that, the
      extract could be applied on mosquito breeding sites. The plant extract could be
      also used for indoor residual sprays after conducting the persistency test. 

PMID- 24751417
TI  - Significant population genetic structure of the Cameroonian fresh water snail,
      Bulinus globosus, (Gastropoda: Planorbidae) revealed by nuclear microsatellite
      loci analysis.
AB  - In order to characterize the demographic traits and spatial structure of
      Cameroonians Bulinus globosus, intermediate host of Schistosoma haematobium,
      genetic structure of seven different populations, collected from the tropical
      zone, was studied using six polymorphic microsatellites. Intrapopulation genetic
      diversity ranged from 0.37 to 0.55. Interpopulation genetic diversity variation
      clearly illustrated their significant isolation due to distance with gene flow
      substantially limited to neighbouring populations. The effective population sizes
      (Ne) were relatively low (from 3.0 to 18.6), which supposes a high rate from
      which populations would lose their genetic diversity by drift. Analysis of
      genetic temporal variability indicated fluctuations of allelic frequencies (35 of
      42 locus-population combinations, P<0.05) characteristic of stochastic
      demography, and this is reinforced by events of bottlenecks detected in all
      populations. These findings demonstrated that Cameroonian B. globosus were mixed
      maters with some populations showing clear preference for outcrossing. These data
      also suggest that genetic drift and gene flow are the main factors shaping the
      genetic structure of studied populations. 

PMID- 24751418
TI  - Eco-social determinants of Schistosoma japonicum infection supported by multi
      level modelling in Eryuan county, People's Republic of China.
AB  - Schistosomiasis remains of considerable public health concern in many tropical
      and subtropical regions of the world, including the People's Republic of China
      (P.R. China). The effectiveness of schistosomiasis control interventions are,
      among other factors, governed by the social-ecological context. However, eco
      social determinants of schistosomiasis are poorly understood, particularly at the
      household or village levels. In the current study, residents in 26 villages of
      Eryuan county, Yunnan province, P.R. China, were screened for Schistosoma
      japonicum infection with a serological assay that was followed by stool
      examination for sero-positive individuals. Bayesian multilevel models with
      spatial random effects were employed to profile the S. japonicum infection risk
      based on known transmission sites of S. japonicum that are scattered across
      individual land parcels in this part of the country. The key risk factors
      identified with this approach were the absence of a sanitary stall house for
      livestock and presence of living and infected intermediate host snails in close
      proximity. We conclude that a spatially explicit Bayesian multilevel approach can
      deepen our understanding of eco-social determinants that govern schistosomiasis
      transmission at a small geographical scale. 

PMID- 24751419
TI  - Population studies of Glossina pallidipes in Ethiopia: emphasis on cuticular
      hydrocarbons and wing morphometric analysis.
AB  - Tsetse flies, like many insects, use pheromones for inter- and intra-specific
      communication. Several of their pheromones are cuticular hydrocarbons (CHCs) that
      are perceived by contact at close range. We hypothesized that for a successful
      implementation of the Sterile Insect Technique (SIT), along with proper
      identification of target area and target species, the target tsetse populations
      and the sterile flies must chemically communicate with each other. To study the
      population structuring of Glossina pallidipes in Ethiopia, CHCs were extracted
      and analyzed from three tsetse belts. As a comparative approach, wing
      morphometric analysis was performed. The analysis of the relative abundance of
      CHCs revealed that populations of G. pallidipes from the Rift Valley tsetse belt
      showed a distinct clustering compared to populations from the other two belts.
      The spatial pattern of CHC differences was complemented by the wing morphometric
      analysis. Our data suggest that CHCs of known biological and ecological role,
      when combined with wing morphometric data, will provide an alternative means for
      the study of population structuring of Glossina populations. This could aid the
      planning of area wide control strategies using SIT, which is dependent on sexual
      competence. 

PMID- 24751420
TI  - Seroepidemiology of selected alphaviruses and flaviviruses in bats in Trinidad.
AB  - A serosurvey of antibodies against selected flaviviruses and alphaviruses in 384
      bats (representing 10 genera and 14 species) was conducted in the Caribbean
      island of Trinidad. Sera were analysed using epitope-blocking enzyme-linked
      immunosorbent assays (ELISAs) specific for antibodies against West Nile virus
      (WNV), Venezuelan equine encephalitis virus (VEEV) and eastern equine
      encephalitis virus (EEEV), all of which are zoonotic viruses of public health
      significance in the region. Overall, the ELISAs resulted in the detection of VEEV
      specific antibodies in 11 (2.9%) of 384 bats. Antibodies to WNV and EEEV were not
      detected in any sera. Of the 384 sera, 308 were also screened using
      hemagglutination inhibition assay (HIA) for antibodies to the aforementioned
      viruses as well as St. Louis encephalitis virus (SLEV; which also causes epidemic
      disease in humans), Rio Bravo virus (RBV), Tamana bat virus (TABV) and western
      equine encephalitis virus (WEEV). Using this approach, antibodies to TABV and RBV
      were detected in 47 (15.3%) and 3 (1.0%) bats, respectively. HIA results also
      suggest the presence of antibodies to an undetermined flavivirus(es) in 8 (2.6%)
      bats. Seropositivity for TABV was significantly (P<0.05; chi2) associated with
      bat species, location and feeding preference, and for VEEV with roost type and
      location. Differences in prevalence rates between urban and rural locations were
      statistically significant (P<0.05; chi2) for TABV only. None of the
      aforementioned factors was significantly associated with RBV seropositivity
      rates.

PMID- 24751421
TI  - Exploring the relationships between health status, illness perceptions, coping
      strategies and psychological morbidity in a chronic kidney disease cohort.
AB  - BACKGROUND: Using the common sense model of illness adjustment, this study aimed
      to explore the impact of chronic kidney disease (CKD) on individual illness
      perceptions, coping styles and psychological well-being. METHODS: Eighty
      individuals (50 men and 30 women) with an average age of 62.66 years (standard
      deviation, 11.98) were included in the study. All participants were under the
      care of the Renal Unit of a metropolitan tertiary referral hospital. Twenty-nine
      patients (36%) had CKD stage 3b-4, and 51 (64%) had CKD stage 5 (or end stage
      kidney disease [ESKD]). Disease severity was evaluated using the health
      perceptions questionnaire, coping styles assessed with the Carver brief COPE
      scale, illness perceptions explored with the brief illness perceptions
      questionnaire and anxiety and depression measured using the hospital anxiety and
      depression scale. RESULTS: The hospital anxiety and depression scale assessment
      revealed 13 patients (16.3%) with moderate or severe anxiety and 6 (7.5%) with
      moderate depression. Consistent with the common sense model, disease activity had
      a significant direct influence on illness perceptions, while, in turn, illness
      perceptions had a significant direct influence on depression and anxiety.
      Adaptive and maladaptive coping were found to mediate the relationship between
      illness perceptions, and anxiety and depression. CONCLUSIONS: The results provide
      evidence that it is the perception of an illness rather than the actual symptoms
      themselves that best account for adaption to CKD. These findings suggest that
      intervention strategies aimed at increasing psychological well-being need to
      focus on changing illness perceptions rather than improving symptoms of CKD or
      coping mechanisms.

PMID- 24751422
TI  - Postinfection immunity to measles was known to common folk well before its
      discovery by science.
AB  - Articles in newspapers and magazines of the early 19th century show that it was
      common knowledge that one only got measles once. This was well before the
      discovery was made by medical science. Even in the 18th century, there was a
      notion that after measles infection, a person was probably immune to it. The
      popular attitude down to the mid-20th century was that the disease was a
      childhood affliction that simply had to be endured.

PMID- 24751423
TI  - A classification scheme for alternative oxidases reveals the taxonomic
      distribution and evolutionary history of the enzyme in angiosperms.
AB  - A classification scheme based on protein phylogenies and sequence harmony method
      was used to clarify the taxonomic distribution and evolutionary history of the
      alternative oxidase (AOX) in angiosperms. A large data set analyses showed that
      AOX1 and AOX2 subfamilies were distributed into 4 phylogenetic clades: AOX1a
      c/1e, AOX1d, AOX2a-c and AOX2d. High diversity in AOX family compositions was
      found. While the AOX2 subfamily was not detected in monocots, the AOX1 subfamily
      has expanded (AOX1a-e) in the large majority of these plants. In addition, Poales
      AOX1b and 1d were orthologous to eudicots AOX1d and then renamed as AOX1d1 and
      1d2. AOX1 or AOX2 losses were detected in some eudicot plants. Several AOX2
      duplications (AOX2a-c) were identified in eudicot species, mainly in the
      asterids. The AOX2b originally identified in eudicots in the Fabales order
      (soybean, cowpea) was divergent from AOX2a-c showing some specific amino acids
      with AOX1d and then it was renamed as AOX2d. AOX1d and AOX2d seem to be stress
      responsive, facultative and mutually exclusive among species suggesting a
      complementary role with an AOX1(a) in stress conditions. Based on the data
      collected, we present a model for the evolutionary history of AOX in angiosperms
      and highlight specific areas where further research would be most beneficial. 

PMID- 24751424
TI  - Genetic experimental preparations for studying atherosclerosis.
AB  - Atherosclerosis is a pathological process with several inputs (biological,
      chemical, physiological, and others) interacting slowly over a lifetime leading
      to coronary artery disease, significant morbidity, and a limited lifespan. Over
      the past two decades, biologists have used experimental preparations from cells,
      animals, and man to understand the biology of atherosclerosis. Much has been
      discovered but our use of the standard gene-targeted experimental preparations is
      now nearing its limit. Better preparations to answer the remaining questions in
      the field of atherosclerosis biology are needed. 

PMID- 24751425
TI  - Genetics of cardiovascular development.
AB  - Structural malformations of the heart are the commonest abnormalities found at
      the time of birth and the incidence is higher in fetuses that are lost during the
      first trimester. Although the form of the heart has been studied for centuries,
      it is in the past decades that the genetic pathways that control heart
      development have been unraveled. Recently, the concept of the second heart field,
      a population of multipotent cardiac cells that augment the initial simple heart
      tube, has clarified the development of the heart. Understanding how the second
      heart field is used in morphogenesis and how genes interact in a subtle and more
      complex way is moving us closer to understanding how the normal heart forms and
      why abnormalities occur. In this chapter, we present a description of the
      morphological processes that create the formed postnatal human heart and
      emphasize key genetic pathways and genes that control these aspects. Where
      possible, these are also linked to the common patterns of human cardiac
      malformation. Undoubtedly, the details will refine or change with further
      research but emphasis has been placed on areas of greatest certainty and the
      presentation designed to promote a general understanding. 

PMID- 24751426
TI  - MicroRNA in pulmonary vascular disease.
AB  - MicroRNA (miRNA) are short noncoding RNA that regulate gene expression by
      inhibiting translation or promoting degradation of target mRNA. miRNA are key
      regulators of a wide range of cellular processes and their discovery has
      revolutionized our understanding of gene regulatory networks. Pulmonary arterial
      hypertension (PAH) is a debilitating and fatal disease characterized by
      remodeling of pulmonary arteries and right heart failure. Factors including
      sustained pulmonary vasoconstriction, inflammation, and altered cellular
      signaling pathways drive disease through pulmonary artery endothelial
      dysfunction, smooth muscle cell proliferation, and the recruitment of circulating
      cells. miRNA have been shown to regulate many of the key drivers of pathology,
      yet the role of only a limited number of miRNA has been recognized in PAH.
      Investigation of the diverse regulatory functions of miRNA offers the potential
      to further understanding of the cellular pathology of PAH and to provide much
      needed diagnostic and therapeutic strategies. This review focuses on recent
      advances in the investigation of miRNA in PAH. 

PMID- 24751427
TI  - Zebrafish as a model of cardiac disease.
AB  - The zebrafish has been rapidly adopted as a model for cardiac development and
      disease. The transparency of the embryo, its limited requirement for active
      oxygen delivery, and ease of use in genetic manipulations and chemical exposure
      have made it a powerful alternative to rodents. Novel technologies like
      TALEN/CRISPR-mediated genome engineering and advanced imaging methods will only
      accelerate its use. Here, we give an overview of heart development and function
      in the fish and highlight a number of areas where it is most actively
      contributing to the understanding of cardiac development and disease. We also
      review the current state of research on a feature that we only could wish to be
      conserved between fish and human; cardiac regeneration. 

PMID- 24751428
TI  - The zebrafish as a model of vascular development and disease.
AB  - The zebrafish has recently emerged as an important animal model to study the
      formation of the vertebrate vascular network. The small size, optical
      translucency, and genetic tractability of the zebrafish embryo, in combination
      with an abundance of fluorescent transgenic lines which permit direct
      visualization of in vivo vessel formation, have greatly advanced our
      understanding of vascular biology. Widespread adoption of this powerful system
      has led to many important discoveries in relation to the mechanisms that underlie
      blood vessel formation. This review highlights the contribution of the zebrafish
      system to the current understanding of blood vessel formation and the use of
      zebrafish to model human vascular disease. 

PMID- 24751429
TI  - Genetics of response to antiplatelet therapy.
AB  - Dual antiplatelet therapy has a major role in the management of acute coronary
      syndromes (ACS) and following percutaneous coronary intervention (PCI). However,
      significant variation in pharmacodynamic response to antiplatelet therapy has
      been demonstrated, especially to clopidogrel. Single nucleotide polymorphisms,
      particularly those affecting the metabolism of antiplatelet therapy, account for
      some, but not all, of this variability in response. Loss-of-function
      polymorphisms of CYP2C19, the gene encoding for the key enzyme in the metabolism
      of clopidogrel, are associated with reduced formation of the active metabolite of
      clopidogrel, a lower pharmacodynamic effect of the drug and a corresponding
      increase in adverse cardiovascular events. Conversely, gain-of-function
      polymorphisms of CYP2C19 are associated with an increased pharmacodynamic
      response to the drug and therefore an increase in bleeding. The clinical
      relevance of other polymorphisms that affect antiplatelet therapy has not been
      clearly established. 

PMID- 24751430
TI  - The role of the transcription factor KLF2 in vascular development and disease.
AB  - The zinc-finger transcription factor KLF2 transduces the physical forces exerted
      by blood flow into molecular signals responsible for a wide range of biological
      responses. Following its initial recognition as a flow-responsive endothelial
      transcription factor, KLF2 is now known to be expressed in a range of cell types
      and to participate in a number of processes during development and disease such
      as endothelial homeostasis, vasoregulation, vascular growth/remodeling, and
      inflammation. In this review, we summarize the current understanding about KLF2
      with a focus on its effects on vascular biology. 

PMID- 24751431
TI  - Preface. Genetics of cardiovascular disease.

PMID- 24751433
TI  - CD4 T-lymphocyte percentages corresponding to CD4 T-lymphocyte count thresholds
      in a new staging system for HIV infection.

PMID- 24751432
TI  - HIV risk reduction with buprenorphine-naloxone or methadone: findings from a
      randomized trial.
AB  - OBJECTIVES: Compare HIV injecting and sex risk in patients being treated with
      methadone (MET) or buprenorphine-naloxone (BUP). METHODS: Secondary analysis from
      a study of liver enzyme changes in patients randomized to MET or BUP who
      completed 24 weeks of treatment and had 4 or more blood draws. The initial 1:1
      randomization was changed to 2:1 (BUP:MET) after 18 months due to higher dropout
      in BUP. The Risk Behavior Survey measured HIV risk before 30 days at baseline and
      weeks 12 and 24. RESULTS: Among 529 patients randomized to MET, 391 (74%) were
      completers; among 740 randomized to BUP, 340 (46%) were completers; 700 completed
      the Risk Behavior Survey. There were significant reductions in injecting risk (P
      < 0.0008) with no differences between groups in mean number of times reported
      injecting heroin, speedball, other opiates, and number of injections; or percent
      who shared needles; did not clean shared needles with bleach; shared cookers; or
      engaged in front/back loading of syringes. The percent having multiple sex
      partners decreased equally in both groups (P < 0.03). For males on BUP, the sex
      risk composite increased; for males on MET, the sex risk decreased resulting in
      significant group differences over time (P < 0.03). For females, there was a
      significant reduction in sex risk (P < 0.02) with no group differences.
      CONCLUSIONS: Among MET and BUP patients who remained in treatment, HIV injecting
      risk was equally and markedly reduced; however, MET retained more patients. Sex
      risk was equally and significantly reduced among females in both treatment
      conditions, but it increased for males on BUP and decreased for males on MET.

PMID- 24751434
TI  - Factors associated with returning to HIV care after a gap in care in New York
      State.
AB  - BACKGROUND: Retention in HIV care has important implications. Few studies
      examining retention include comprehensive and heterogeneous populations, and few
      examine factors associated with returning to care after gaps in care. We
      identified reasons for gaps in care and factors associated with returning to
      care. METHODS: We extracted medical record and state-wide reporting data from
      1865 patients with 1 HIV visit to a New York facility in 2008 and subsequent 6
      month gap in care. Using mixed effect logistic regression, we examined
      sociodemographic, clinical, and facility characteristics associated with
      returning to care. RESULTS: Most patients were men (63.2%), black (51.4%), had
      Medicaid (53.9%). Many had CD4 counts >500 cells per cubic millimeter (34.4%) and
      undetectable viral loads (45.0%). Most (55.9%) had unknown reasons for gaps in
      care; of those with known reasons, reasons varied considerably. After a gap,
      54.6% returned to care. Patients who did (vs. did not) return to care were more
      likely to have stable housing, longer duration of HIV, high CD4 count, suppressed
      viral load, antiretroviral medications, and had facilities attempt to contact
      them. Those who returned to care were less likely to be uninsured and have mental
      health problems or substance use histories. CONCLUSION: Over half of our sample
      of patients in New York with 1 HIV visit and subsequent 6-month gap in care
      returned to care; no major reasons for gaps emerged. Nevertheless, our findings
      emphasize that stabilizing patients' psychosocial factors and contacting patients
      after a gap in care are key strategies to retain HIV-positive patients in care in
      New York.

PMID- 24751435
TI  - PLE-wu, a new member of piggyBac transposon family from insect, is active in
      mammalian cells.
AB  - piggyBac, a highly active transposon in insect and mammalian cells, is a very
      useful tool in genome manipulation. A new piggyBac-like element (PLE), named PLE
      wu, was identified from a mutant baculovirus cultured in sf9 insect cells. This
      new transposon is 2931 bp in length and encodes two active forms of transposase,
      a 708-amino acid-long transposase and a short 576-residue-long transposase
      translated from a downstream in-frame initiation codon. PLE-wu has asymmetric
      terminal structures, containing 6-bp inverted terminal repeats, 32-bp imperfect
      inverted and direct sub-terminal repeats. Similar to piggyBac, PLE-wu exhibits
      traceless excision activity in both insect and mammalian cells, restoring the
      original TTAA target sequence upon excision. It also retains the insertion
      activity in mammalian cells with a plasmid to chromosome transposition rate about
      10-fold higher than random integration. Plasmid rescue assays revealed that the
      TTAA target sequence was duplicated at the junctions of the insertion site.
      Deletion of the terminal sequences including the sub-terminal repeats decreased
      the transposition activity of the 708-residue-long transposase, while the
      transposition activity of the short form of transposase was not affected. With
      its low sequence similarity to piggyBac, PLE-wu will contribute to the
      understanding the mechanism of PLE transposition, as well as design of new
      transposon systems with higher activity. 

PMID- 24751436
TI  - Molybdenum-containing membrane-bound formate dehydrogenase isolated from
      Citrobacter sp. S-77 having high stability against oxygen, pH, and temperature.
AB  - Membrane-bound formate dehydrogenase (FDH) was purified to homogeneity from a
      facultative anaerobic bacterium Citrobacter sp. S-77. The FDH from Citrobacter
      sp. S-77 (FDHS77) was a monomer with molecular mass of approximately 150 kDa. On
      SDS-PAGE, the purified FDHS77 showed as three different protein bands with
      molecular mass of approximately 95, 87, and 32 kDa, respectively. Based on the N
      terminal amino acid sequence analysis, the sequence alignments observed for the
      87 kDa protein band were identical to that of the large subunit of 95 kDa,
      indicating that the purified FDHS77 consisted of two subunits; a 95 kDa large
      subunit and a 32 kDa small subunit. The purified FDHS77 in this purification did
      not contain a heme b subunit, but the FDHS77 showed significant activity for
      formate oxidation, determined by the Vmax of 30.4 U/mg using benzyl viologen as
      an electron acceptor. The EPR and ICP-MS spectra indicate that the FDHS77 is a
      molybdenum-containing enzyme, displaying a remarkable O2-stability along with
      thermostability and pH resistance. This is the first report of the purification
      and characterization of a FDH from Citrobacter species. 

PMID- 24751438
TI  - Chemotherapy-associated oral sequelae in patients with cancers outside the head
      and neck region.
AB  - CONTEXT: Chemotherapy induces a wide array of acute and late oral adverse effects
      that makes symptom alleviation and information important parts of patient care.
      OBJECTIVES: To assess the prevalence and intensity of acute oral problems in
      outpatients receiving chemotherapy for cancers outside the head and neck region
      and to investigate if information about possible oral adverse effects was
      received by the patients. METHODS: In this cross-sectional study, outpatients
      aged 18 years or older were invited to participate and included if they fulfilled
      the inclusion criteria. All patients completed the Edmonton Symptom Assessment
      System, participated in a semistructured interview, and underwent an oral
      examination by a dentist. RESULTS: Of 226 eligible patients, 155 (69%)
      participated. Mean age was 57 years, and 34% were males. The most prevalent
      diagnoses were breast (45%) and gastrointestinal cancers (37%). Xerostomia was
      reported by 59%, taste changes by 62%, oral discomfort by 41%, and 27% had
      problems eating. Fatigue (3.4) and xerostomia (3.1) received the highest
      intensity scores on the Edmonton Symptom Assessment System. Oral candidiasis
      confirmed by positive cultures was seen in 10%. Twenty-seven percent confirmed
      that they had received information on oral adverse effects of cancer treatment.
      CONCLUSION: Oral sequelae were frequently reported, and health care providers
      should be attentive to the presence and severity of these problems. Less than one
      third of the patients remembered having received information about oral sequelae
      associated with chemotherapy. A continuous focus on how to diagnose, manage, and
      inform about oral cancer-related complications is advisable.

PMID- 24751437
TI  - Palliative sedation at home for terminally ill children with cancer.
AB  - CONTEXT: The presence of symptoms that are difficult to control always requires
      adjustment of treatment, and palliative sedation (PS) should be considered.
      OBJECTIVES: We analyzed our experience in conducting PS at home for terminally
      ill children with cancer during a seven-year period. METHODS: We performed a
      retrospective analysis of medical records of children with cancer treated at home
      between the years 2005 and 2011. RESULTS: We analyzed the data of 42 cancer
      patients (18% of all patients); in 21 cases, PS was initiated (solid tumors n =
      11, brain tumors [5], bone tumors [4], leukemia [1]). Sedation was introduced
      because of pain (n = 13), dyspnea (9), anxiety (5), or two of those symptoms (6).
      The main drug used for sedation was midazolam; all patients received morphine.
      There were no significant differences in the dose of morphine or midazolam
      depending on the patient's sex; age was correlated with an increase of midazolam
      dose (R = 0.68; P = 0.005). Duration of sedation (R = 0.61; P = 0.003) and its
      later initiation (R = 0.43; P = 0.05) were correlated with an increase of the
      morphine dose. All patients received adjuvant treatment; in patients who required
      a morphine dose increase, metoclopramide was used more often (P = 0.0002).
      Patients did not experience any adverse reactions. Later introduction of sedation
      was associated with a marginally higher number of intervention visits and a
      significantly higher number of planned visits (R = 0.53; P = 0.013). CONCLUSION:
      Sedation may be safely used at home. It requires close monitoring and full
      cooperation between the family and hospice team. Because of the limited data on
      home PS in pediatric populations, further studies are needed.

PMID- 24751439
TI  - Synthesis, anti-HIV and cytostatic evaluation of 3'-deoxy-3'-fluorothymidine
      (FLT) pro-nucleotides.
AB  - A series of pro-nucleotide phosphoramidates and phosphorodiamidates of the
      antiviral lead compound 3'-deoxy-3'-fluorothymidine (FLT) have been designed and
      synthesized. In vitro antiretroviral and cytostatic studies revealed potent (sub
      micromolar) inhibition of HIV-1 and HIV-2 replication, with retention of activity
      in thymidine kinase-negative cell models, as predicted by the ProTide concept. 

PMID- 24751440
TI  - Optimization of pancreatic lipase inhibition by Cudrania tricuspidata fruits
      using response surface methodology.
AB  - The fruits of Cudrania tricuspidata (Carr.) Bur. (Moraceae) significantly
      inhibited pancreatic lipase, which plays a key role in fat absorption.
      Optimization of extraction conditions with minimum pancreatic lipase activity and
      maximum yield was determined using response surface methodology with three-level
      three-factor Box-Behnken design (BBD). Regression analysis showed a good fit of
      the experimental data and the optimal condition was obtained as ethanol
      concentration, 74.5%; temperature 61.9 degrees C and extraction time, 13.5h. The
      pancreatic lipase activity and extraction yield under optimal conditions were
      found to be 65.5% and 54.0%, respectively, which were well matched with the
      predicted value of 65.8% and 47.1%. Further fractionation of C. tricuspidata
      extract resulted in the isolation of compound 1, which was identified as 5,7,4'
      trihydroxy-6,8-diprenylisoflavone. It inhibited pancreatic lipase activity with
      IC50 value of 65.0MUM. HPLC analysis suggested positive correlation between
      pancreatic lipase inhibition and 5,7,4'-trihydroxy-6,8-diprenylisoflavone of C.
      tricuspidata fruits. 

PMID- 24751441
TI  - Identification of a new series of potent diphenol HSP90 inhibitors by fragment
      merging and structure-based optimization.
AB  - Heat shock protein 90 (HSP90) is a molecular chaperone to fold and maintain the
      proper conformation of many signaling proteins, especially some oncogenic
      proteins and mutated unstable proteins. Inhibition of HSP90 was recognized as an
      effective approach to simultaneously suppress several aberrant signaling
      pathways, and therefore it was considered as a novel target for cancer therapy.
      Here, by integrating several techniques including the fragment-based drug
      discovery method, fragment merging, computer aided inhibitor optimization, and
      structure-based drug design, we were able to identify a series of HSP90
      inhibitors. Among them, inhibitors 13, 32, 36 and 40 can inhibit HSP90 with IC50
      about 20-40 nM, which is at least 200-fold more potent than initial fragments in
      the protein binding assay. These new HSP90 inhibitors not only explore
      interactions with an under-studied subpocket, also offer new chemotypes for the
      development of novel HSP90 inhibitors as anticancer drugs.

PMID- 24751442
TI  - Design and synthesis of new vancomycin derivatives.
AB  - A set of vancomycin derivatives with lipid chain attached via a glyceric acid
      linker was designed and synthesized. A concise synthesis towards these
      derivatives was developed and the IC50s of these new lipoglycopeptides were
      tested. Some of them showed very potent activity against both vancomycin
      sensitive and resistant strains. 

PMID- 24751443
TI  - Discovery of structurally novel, potent and orally efficacious GPR119 agonists.
AB  - Screening hit 5 was identified in a biochemical screen for GPR119 agonists.
      Compound 5 was structurally novel, displayed modest biochemical activity and no
      oral exposure, but was structurally distinct from typical GPR119 agonist
      scaffolds. Systematic optimization led to compound 36 with significantly improved
      in vitro activity and oral exposure, to elevate GLP1 acutely in an in vivo mouse
      model at a dose of 10mg/kg. 

PMID- 24751444
TI  - The antibacterial properties of sulfur containing flavonoids.
AB  - Some dithiocarbamic esters bearing a flavanone backbone, as well as their
      corresponding 1,3-dithiolium salts were tested against Staphylococcus aureus and
      Escherichia coli. The 1,3-dithiolium tricyclic flavonoids display good inhibitory
      properties against both Gram-positive and Gram-negative pathogens. 

PMID- 24751445
TI  - Hot spot-based design of small-molecule inhibitors for protein-protein
      interactions.
AB  - Protein-protein interactions (PPIs) are important targets for the development of
      chemical probes and therapeutic agents. From the initial discovery of the
      existence of hot spots at PPI interfaces, it has been proposed that hot spots
      might provide the key for developing small-molecule PPI inhibitors. However,
      there has been no review on the ways in which the knowledge of hot spots can be
      used to achieve inhibitor design, nor critical examination of successful
      examples. This Digest discusses the characteristics of hot spots and the
      identification of druggable hot spot pockets. An analysis of four examples of hot
      spot-based design reveals the importance of this strategy in discovering potent
      and selective PPI inhibitors. A general procedure for hot spot-based design of
      PPI inhibitors is outlined. 

PMID- 24751446
TI  - Cell permeable vanX inhibitors as vancomycin re-sensitizing agents.
AB  - VanX is an induced zinc metallo d-Ala-d-Ala dipeptidase involved in the viable
      remodeling of bacterial cell wall that is essential for the development of VREF.
      Here we report two cyclic thiohydroxamic acid-based peptide analogs that were
      designed, synthesized and investigated as vancomycin re-sensitizing agents. These
      compounds exhibit low micromolar inhibitory activity against vanX, with low
      cytotoxicity and were shown to increase vancomycin sensitivity against VREF. The
      improved pharmacological properties of these novel inhibitors over previous
      transition state mimics should provide an enhanced platform for designing potent
      vanX inhibitors for overcoming vancomycin resistance. 

PMID- 24751447
TI  - Scadding revisited: a proposed staging system for cardiac sarcoidosis.

PMID- 24751448
TI  - How many organs need to be involved to diagnose sarcoidosis?: An unanswered
      question that, hopefully, will become irrelevant.

PMID- 24751449
TI  - Multi-dimensional indices to stage idiopathic pulmonary fibrosis: a systematic
      review.
AB  - Idiopathic pulmonary fibrosis (IPF) has the highest mortality rate among all
      interstitial lung diseases, with a mean survival time of 2 to 3 years from the
      time of diagnosis. Prognosis is difficult to determine, due to the recognized
      heterogeneous progression of the disease, as well as lack of a well recognized
      staging system. This in turn raises challenges when considering therapeutic
      options for IPF patients, such as lung transplantation, versus a more
      conservative approach.  Multiple independent factors have been identified as
      prognostic indicators in IPF, and a number of studies have proposed multi
      dimensional indices that combine several parameters in order to achieve a more
      accurate delineation of disease progression. In this systematic review, the
      Pubmed database was used to identify studies in the area of multi-dimensional
      staging of IPF.  We analysed and critically appraised previously proposed
      prognostic scoring systems. Our aim is to encourage research developments in this
      area to help identify an optimal multi-dimensional staging system for IPF. 

PMID- 24751450
TI  - The WASOG Sarcoidosis Organ Assessment Instrument: An update of a previous
      clinical tool.
AB  - INTRODUCTION: A Case Control Etiology of Sarcoidosis Study (ACCESS) sarcoidosis
      organ assessment instrument has been used for more than a decade to establish
      uniform standards for the probability of sarcoidosis organ involvement. The
      ACCESS instrument has become increasingly outdated as new technologies have been
      developed. Furthermore, the ACCESS instrument failed to address all possible
      organs involved with sarcoidosis. For these reasons, the World Association of
      Sarcoidosis and Other Granulomatous Diseases (WASOG) developed a new sarcoidosis
      organ assessment instrument. METHODS: Clinical sarcoidosis experts assessed
      various clinical manifestations for the probability of sarcoidosis organ
      involvement. Two criteria were required to apply this assessment: 1) histologic
      evidence of granulomatous inflammation of unknown cause in an organ that was not
      being assessed; 2) the clinical manifestation being addressed required that
      alternative causes other than sarcoidosis had been reasonably excluded. Clinical
      manifestations were assessed as either: a) highly probable: likelihood of
      sarcoidosis causing this manifestation of at least 90%.; b) probable: likelihood
      of sarcoidosis causing this manifestation of between 50 and 90%; c) possible:
      likelihood of sarcoidosis causing this manifestation of less than 50%. The
      sarcoidosis experts voted on the likelihood of sarcoidosis causing each
      manifestation using Delphi study methodology where at least 70% agreement of the
      experts was needed for consensus. RESULTS: Various clinical manifestations were
      classified as highly probable, at least probable, possible, or indeterminate when
      no consensus could be reached. CONCLUSION: An instrument was developed by expert
      opinion that may be useful for the clinician and researcher in establishing
      criteria for sarcoidosis organ involvement.

PMID- 24751451
TI  - Features and outcome of familial idiopathic pulmonary fibrosis.
AB  - BACKGROUND: Idiopathicpulmonary fibrosis (IPF) has a sporadic occurrence in most
      instances,but can also occasionally occur in familial form. While
      clinicalfeatures of sporadic IPF are well defined, clinical
      presentation,complications, and outcome of familial IPF are still undefined.
      Thisretrospective study was undertaken to establish clinical parametersand
      survival time in a consecutive series of patients with familialIPF and to
      establish whether the phenomenon of anticipation could beobserved. METHODS: 30
      patients had received a diagnosis of familial IPF at ourinstitution over the
      period from January 2005 and December 2011; in7 of them there was a parent-child
      relation.Clinical features and patient outcome were analyzed and contrasted toa
      well characterized cohort of 127 patients with non familial IPF. RESULTS: there
      was no significant difference in presenting symptoms and theoverall outcomes were
      quite similar in the two groups, but thefamilial group was much more enriched for
      females and we found astatistically significant lower age at onset in the
      youngergenerations (mean age 57,8 years versus 74,2 years, p 0,001).
      Acuteexacerbations, IPF progression and lung cancer were more frequent inthe
      familial IPF group as a cause of death (p < 0,005). CONCLUSION: familial IPF
      seems indistinguishable from sporadic IPF with respectto most clinical and
      physiologic findings; however the age of onsetwas slightly lower among the
      familial cases than in the sporadiccases of IPF and the phenomenon of
      anticipation could be observed.

PMID- 24751452
TI  - Extent of disease activity assessed by 18F-FDG PET/CT in a Dutch sarcoidosis
      population.
AB  - BACKGROUND: Sarcoidosis is characterized by a wide range of disease
      manifestations. In the management and follow-up of sarcoidosis patients,
      knowledge of extent of disease, activity and severity is crucial. Objectives The
      aim of this study was to assess the extent, distribution and consistency of
      inflammatory organ involvement using 18F-FDG PET/CT (PET) in sarcoidosis patients
      with persistent disabling symptoms. METHODS: Retrospectively, sarcoidosis
      patients who underwent a PET between 2005 and 2011 (n=158) were included.
      Clinical data were gathered from medical records and PET scans were evaluated.
      Positive findings were classified as thoracic and/or extrathoracic. RESULTS :Of
      the studied PET positive sarcoidosis patients (n=118/158; 75%), 93% had
      intrathoracic activity (79% mediastinal and 64% pulmonary activity, respectively)
      and 75% displayed extrathoracic activity (mainly peripheral lymph nodes,
      bone/bone marrow, and spleen). Hepatic positivity was always accompanied by
      splenic activity, whereas the majority of patients with parotid gland, splenic or
      bone/bone marrow activity showed lymph node activity. A substantial number of
      patients with PET positive pulmonary findings (86%) had signs of respiratory
      functional impairment. No obvious association between hepatic, splenic or
      bone/bone marrow activity and their corresponding laboratory abnormalities
      suggestive of specific organ involvement, was found. CONCLUSIONS: The majority of
      studied patients appeared to have PET positive findings (75%), of which a high
      proportion (75%) displayed extrathoracic activity. Hence, PET can be especially
      useful in the assessment of extent, distribution and consistency of inflammatory
      activity in sarcoidosis to provide an explanation for persistent disabling
      symptoms and/or to provide a suitable location for biopsy.

PMID- 24751454
TI  - Decreased sputum caveolin-1 is associated with systemic sclerosis related lung
      disease.
AB  - AIM: To determine serum and sputum Caveolin-1 (Cav-1) levels and their
      associations with transforming growth factor- beta (TGF-beta) and interstitial
      lung disease (ILD) in systemic sclerosis (SSc). METHODS: Serum and induced sputum
      samples from 55 patients with SSc, 25 asthma patients and 16 healthy volunteers
      (HC) were tested for Cav-1 and TGF-beta by the ELISA technique. As a possible
      downstream signaling regulator of TGF-beta, Endothelin-1 (ET-1), a potent
      profibrotic protein, was also measured in all serum and sputum samples and
      relations with Cav-1 and TGF-beta were sought. All scleroderma patients were
      evaluated for their clinical and laboratory parameters. Pulmonary function tests
      (PFT) and high resolution computerized tomography (HRCT) were performed for the
      diagnosis of ILD. The alveolitis-fibrosis index and the SSc disease severity
      scores were noted for each patient. RESULTS: Serum Cav-1 levels were lower in SSc
      compared to HC (p<0.01). Cav-1 levels were significantly lower in the sputum of
      SSc patients compared to both control groups (p<0.001). It was also found
      significantly lower in SSc-ILD compared to those without ILD (0.19+/-0.04 vs
      0.25+/-0.07, respectively, p<0.01). Although no difference was found in the serum
      TGF-beta levels among the groups, sputum TGF-beta levels correlated positively
      with the alveolitis index (r=0.34) and correlated inversely with FVC measurements
      (r=-0.44, p<0.05) among SSc patients. Serum ET-1 was significantly higher in SSc
      patients (p<0.01) but no association was found between ET-1 and Cav-1 or TGF
      beta. CONCLUSION: These results suggest that decreased sputum Cav-1 levels is
      associated with SSc related-ILD and may be used as a marker for the detection of
      SSc-ILD.

PMID- 24751453
TI  - Efficacy Results of a 52-week Trial of Adalimumab in the Treatment of Refractory
      Sarcoidosis.
AB  - BACKGROUND: Infliximab, a chimeric, monoclonal, anti-TNF antibody has been shown
      to be safe and efficacious for refractory sarcoidosis, we investigated whether
      adalimumab, a fully human, anti-TNF monoclonal antibody, is similarly safe and
      efficacious in refractory pulmonary sarcoidosis. METHODS: An open-label, single
      center study was conducted in 11 patients with refractory pulmonary sarcoidosis.
      Patients received adalimumab 40 mg weekly for 45 weeks, with a final follow-up at
      Week 52. The primary endpoint was the percent change in predicted forced vital
      capacity (FVC) at 24 weeks. Secondary efficacy parameters included the 6-minute
      walk test (6MWT), Borg dyspnea score, and Physician's (PGA) and Patient's (PaGA)
      Global Assessments. A successful outcome of the study was defined as reduction in
      immunosuppressive therapy (prednisone to 10 mg or less), improvement in FVC of 5%
      or greater, improvement in 6-minute walk test distance (6MWD) of 50 meter or
      greater at the end of weeks 24 and 52. RESULTS: Eleven patients received
      adalimumab and had 24-week follow-ups. Only ten patients had a Week 52
      evaluation. FVC stabilized in seven patients, and four patients showed
      improvement in FVC. Five patients had improved 6MWD, and nine had lower Borg
      dyspnea scores. PGA and PaGA improved at weeks 24 and 52 for all patients
      (P<0.008 for all comparisons). Among 11 patients who underwent adalimumab
      treatment, 9 (82%) and 8(80%) had a successful outcome at the end of 24 and 52
      weeks respectively. No severe adverse incidents were reported. CONCLUSIONS: In
      this small, open-label study, adalimumab improved refractory pulmonary
      sarcoidosis and was well tolerated (ClinicalTrials.gov identifier NCT00311246).

PMID- 24751455
TI  - New brain lesions in a patient with sarcoidosis: is it neurosarcoidosis?
AB  - A 45-year-old woman with pulmonary sarcoidosis diagnosed 5 years previously, who
      was on treatment with prednisone and methotrexate for 1year, developed partial
      seizure with secondary generalization. MRI showed three non-cavitary enhancing
      lesions in the cerebello-occipital region. These lesions were presumed to be
      neurosarcoidosis. Methotrexate was discontinued, prednisone dose was increased
      and azathiopurine and levetiracetam were added. While on treatment, follow up
      imaging showed enlarging brain lesions. Biopsy of the lesions showed Epstein Barr
      virus (EBV) positive diffuse B cell lymphoma. Immunosuppressants were tapered off
      and she was begun on Rituximab. Because of lack of improvement after 4 cycles of
      Rituximab, she was then treated with high dose Methotrexate and Temozolamide. We
      present this case as a diagnostic challenge. New enhancing brain lesions
      occurring in a patient with long standing sarcoidosis, while likely to be
      neurosarcoidosis, may be due to a complication of immunosuppressant therapy. The
      need for early biopsy, if the lesions do not improve, should be considered. 

PMID- 24751456
TI  - Expect the unexpected: unusual neurological presentation of bone marrow
      sarcoidosis.
AB  - Bone marrow granulomas are rare and, when they occur, sarcoidosis is an uncommon
      etiology. This report describes a case of a 58-year-old man who presented with a
      five-month history of bilateral lower limb paresis. His paresis was associated
      with urinary and fecal incontinence and impotence, but without any loss of
      sensations. Head, chest, abdominal, and pelvic CT scans and MRI images, and a
      full-body Gallium 67 scan were all within normal limits. A CT-guided biopsy of
      the L1-L2 vertebral bodies showed non-caseating granulomatous inflammation. Serum
      angiotensin-converting enzyme (ACE) level was elevated. A diagnosis of bone
      marrow sarcoidosis was made after other differential diagnoses were excluded. 

PMID- 24751457
TI  - An unusual manifestation of Cardiac Sarcoidosis.
AB  - Non tropical, non hypereosinophilic endo myocardial fibrosis has been reported in
      literature and is a rare entity.  Cardiac Sarcoidosis manifesting as non
      tropical, non hypereosinophilic endomyocardial fibrosis is unknown, though it
      classically affects the left ventricle and is not associated with specific risk
      factors. We describe an atypical presentation of sarcoidosis as non-tropical non
      hypereosinophilic endomyocardial fibrosis in a middle aged female who presented
      to us with refractory heart failure. 

PMID- 24751458
TI  - Psychosis: a rare but serious psychiatric anomaly in patients with sarcoidosis.

PMID- 24751460
TI  - Post-traumatic lower cervical spine instability: arthrodesis clinical and
      radiological outcomes at 5 years.
AB  - BACKGROUND: Anterior cervical fusion is widely used to treat spinal injuries.
      Radiological evidence of disc abnormalities may develop on either side of the
      fused segment, raising concern about the potential for inducing adjacent-segment
      disease. Here, we report the long-term clinical, functional, and radiological
      outcomes after anterior cervical fusion. HYPOTHESIS: Anterior cervical fusion
      influences the development of adjacent-segment disease. MATERIALS AND METHODS: In
      a retrospective study, 15 patients aged 17 to 50 years were re-evaluated more
      than 5 years after anterior spinal fusion to treat post-traumatic cervical-spine
      instability. We used the Neck Disability Index (NDI) to assess function. Static
      and dynamic radiographs of the cervical spine were obtained. RESULTS: NDI values
      indicated good clinical and functional outcomes, and fusion was achieved
      consistently. Adjacent-segment disease was a consistent finding at last follow-up
      but induced no neurological manifestations. Complete fusion of a level adjacent
      to the treated level was noted in 2 patients. Revision surgery for adjacent
      segment disease was not required in any patient. CONCLUSION: The causative
      factors of adjacent-segment disease are controversial. Disc degeneration is a
      normal manifestation of the ageing process. Nevertheless, disc disease is more
      prevalent at levels adjacent to interbody fusion than in the normal population,
      suggesting accelerated disc degeneration due to increased loading of the adjacent
      levels. Furthermore, lesions that are missed during the pre-operative work-up may
      play a role, as the available investigations do not always have high negative
      predictive values. LEVEL OF EVIDENCE: Level IV, retrospective study.

PMID- 24751459
TI  - Degrees of kidney disease in nigerian adults with sickle-cell disease.
AB  - OBJECTIVE: To study degrees of chronic kidney disease (CKD) using creatinine
      clearance in adult Nigerian patients with sickle-cell disease (SCD). METHODS: One
      hundred SCD patients, made up of 79 HbSS (homozygous haemoglobin S) patients and
      21 HbSC (heterozygous haemoglobins S and C) patients, were investigated
      prospectively, along with 50 normal controls. Their sociodemographic data, weight
      and drug history were documented. Each participant underwent dipstick urinalysis,
      and creatinine clearance was calculated following a 24-hour urine collection and
      serum creatinine measurement. They were categorized into stages of CKD based on
      the creatinine clearance. RESULTS: Of the 79 HbSS patients, 14 (18%), 28 (35%),
      33 (42%) and 4 (5%) had stage 1, 2, 3 and 4 CKD, respectively. In the HbSC group,
      3 (14%), 9 (43%) and 9 (43%) patients had stage 1, 2 and 3 CKD, respectively.
      Proteinuria was noted in 16 (20%) HbSS patients but not in any of the HbSC
      patients. Of the subjects aged <=24 years (n = 49), 9 (18%), 18 (37%), 21 (43%)
      and 1 (2%) had stage 1, 2, 3 and 4 CKD, respectively. Of those aged >24 years (n
      = 51), 8 (16%), 19 (37%), 21 (41%) and 3 (6%) had stage 1, 2, 3 and 4 CKD,
      respectively. None of the subjects had stage 5 CKD. CONCLUSION: In this study,
      the adult subjects with SCD had various degrees of CKD. Adequate follow-up and
      active intervention are advocated to delay the onset of end-stage nephropathy.

PMID- 24751461
TI  - Juvenile hypomyopathic dermatomyositis initiating with acquired inflammatory
      Blaschko-linear dermatosis.

PMID- 24751462
TI  - Efficacy of intravenous levosimendan in patients with heart failure complicated
      by acute myocardial infarction.
AB  - OBJECTIVES: To evaluate the efficacy of a short-term intravenous infusion of
      levosimendan in patients with heart failure due to acute myocardial infarction
      (AMI). METHODS: This was a randomized, single-center, single-blind study that
      included 160 patients. Patients were randomly divided into 2 groups: 1 received
      levosimendan (n = 80) and the other received placebo (n = 80). The study included
      multiple primary end points (death, myocardial ischemia or worsening heart at the
      6 month follow-up) and used a composite outcome. RESULTS: The primary end point
      rate in the levosimendan group was lower than that in placebo group (43.7 vs.
      62.5%, HR 0.636, 95% CI 0.413-0.981, p = 0.041). Moreover, the mortality rate at
      6 months was similar between the 2 groups (17.5 vs. 22.5%, HR 0.786, 95% CI 0.382
      1.543, p = 0.458). There was a higher incidence of myocardial ischemia in the
      levosimendan group at 14 days than in the placebo group (11.2 vs. 7.5%, HR 1.510,
      p = 0.435), but between 15 and 180 days, it was significantly lower in the
      levosimendan group than in the placebo group (3.8 vs. 13.8%, HR 0.261, p =
      0.036). CONCLUSION: Short-term intravenous infusion of levosimendan appears to be
      more effective than placebo for treating patients with heart failure complicated
      by AMI.

PMID- 24751463
TI  - Dorsal rhizotomy for pain from neoplastic lumbosacral plexopathy in advanced
      pelvic cancer.
AB  - BACKGROUND: Pain from neoplastic lumbosacral plexopathy is resistant to
      conventional pain treatment. According to a recent review of destructive
      procedures for cancer pain, only cordotomy has been reported to play an important
      role in the treatment of cancer pain. To date, the effectiveness of dorsal
      rhizotomy, which selectively interrupts pain transmission, has not been shown in
      neoplastic lumbosacral plexopathy. OBJECTIVES: The present study seeks to find
      out the effectiveness of selective dorsal rhizotomies for intractable pain from
      neoplastic lumbosacral plexopathy in terminal pelvic cancer patients. METHODS:
      Dorsal rhizotomies of the involved segments were performed on 6 cancer patients
      in whom neuropathic pain from lumbosacral plexus involvement in terminal pelvic
      cancer had been refractory to other therapies. Clinical efficacy of the procedure
      was assessed by comparing patient pain ratings and narcotic usage before and
      after dorsal rhizotomy. RESULTS: Examination of the results indicated a
      significant reduction in pain ratings as well as a significant reduction in daily
      narcotic use. No adverse neurological effects were observed and no recurrence of
      pain from neoplastic lumbosacral plexopathy was noted. CONCLUSIONS: These
      findings provide corroborating clinical evidence for the effectiveness of
      selective dorsal root rhizotomy for the intractable pain from lumbosacral
      plexopathy in terminal pelvic cancer patients.

PMID- 24751464
TI  - Social heuristics shape intuitive cooperation.
AB  - Cooperation is central to human societies. Yet relatively little is known about
      the cognitive underpinnings of cooperative decision making. Does cooperation
      require deliberate self-restraint? Or is spontaneous prosociality reined in by
      calculating self-interest? Here we present a theory of why (and for whom)
      intuition favors cooperation: cooperation is typically advantageous in everyday
      life, leading to the formation of generalized cooperative intuitions.
      Deliberation, by contrast, adjusts behaviour towards the optimum for a given
      situation. Thus, in one-shot anonymous interactions where selfishness is optimal,
      intuitive responses tend to be more cooperative than deliberative responses. We
      test this 'social heuristics hypothesis' by aggregating across every cooperation
      experiment using time pressure that we conducted over a 2-year period (15 studies
      and 6,910 decisions), as well as performing a novel time pressure experiment.
      Doing so demonstrates a positive average effect of time pressure on cooperation.
      We also find substantial variation in this effect, and show that this variation
      is partly explained by previous experience with one-shot lab experiments. 

PMID- 24751465
TI  - Urban prevalence of Listeria spp. and Listeria monocytogenes in public lavatories
      and on shoe soles of facility patrons in the European capital city Vienna.
AB  - The aim of this study was to determine the prevalence of Listeria spp. and
      Listeria monocytogenes (L. monocytogenes) in urban public lavatories and on shoe
      soles of facility patrons in a European capital city. More than 91% of all
      municipal public lavatories in Vienna close to public hubs were included in this
      study. Overall, 373 swab samples of public lavatories and shoes of facility
      patrons were enriched, according to ISO 11290-1. Listeria monocytogenes isolates
      were subtyped using pulsed-field gel electrophoresis. A total of 24 samples were
      positive for Listeria spp., yielding an overall prevalence of 6.4% (24/373).
      Listeria monocytogenes was found in 2.1% (8/373) of all samples. Swabs from
      lavatories in parks, container lavatories and lavatories at markets had the
      highest prevalences of 20.7% (6/29), 20% (2/10) and 12.5% (1/8) Listeria spp.,
      respectively. These detection rates were statistically significantly higher than
      those associated with lavatories in shopping centres (P = 0.003, P = 0.002, P =
      0.02) and at public transport locations (P = 0.0004, P = 0.005, P = 0.02). Shoes
      sampled at Christmas markets showed the highest Listeria spp. and L.
      monocytogenes prevalences of 80% (4/5) and 40% (2/5), respectively. With regard
      to shoe type, Listeria spp. detection rates were 14.3% (3/21; winter boots),
      13.3% (2/15; hiking boots), sport shoes (5.9%; 2/34) and brogues (5.1%; 4/79). No
      Listeria spp. were found on shoe soles that had smooth treads (0/76), while
      Listeria spp. were detected on 19.5% (8/41) of medium depth tread shoe types and
      on 9.4% (3/32) of deep tread shoes. These data suggest that soil environment is
      still one of the most important reservoirs for the foodborne pathogen L.
      monocytogenes.

PMID- 24751466
TI  - Evaluating factor XIII specificity for glutamine-containing substrates using a
      matrix-assisted laser desorption/ionization time-of-flight mass spectrometry
      assay.
AB  - Activated factor XIII (FXIIIa) catalyzes the formation of gamma-glutamyl-epsilon
      lysyl cross-links within the fibrin blood clot network. Although several cross
      linking targets have been identified, the characteristic features that define
      FXIIIa substrate specificity are not well understood. To learn more about how
      FXIIIa selects its targets, a matrix-assisted laser desorption/ionization time-of
      flight mass spectrometry (MALDI-TOF MS)-based assay was developed that could
      directly follow the consumption of a glutamine-containing substrate and the
      formation of a cross-linked product with glycine ethylester. This FXIIIa kinetic
      assay is no longer reliant on a secondary coupled reaction, on substrate
      labeling, or on detecting only the final deacylation portion of the
      transglutaminase reaction. With the MALDI-TOF MS assay, glutamine-containing
      peptides derived from alpha2-antiplasmin, Staphylococcus aureus fibronectin
      binding protein A, and thrombin-activatable fibrinolysis inhibitor were examined
      directly. Results suggest that the FXIIIa active site surface responds to changes
      in substrate residues following the reactive glutamine. The P-1 substrate
      position is sensitive to charge character, and the P-2 and P-3 substrate
      positions are sensitive to the broad FXIIIa substrate specificity pockets. The
      more distant P-8 to P-11 region serves as a secondary substrate anchoring point.
      New knowledge on FXIIIa specificity may be used to design better substrates or
      inhibitors of this transglutaminase.

PMID- 24751468
TI  - Confirmation of the validity of the current characterization of immunochemical
      reactions by kinetic exclusion assay.
AB  - Prior observations that questioned the validity of kinetic exclusion assays were
      based on the mistaken assumption that the assays quantified the fraction of those
      antibody molecules that had unoccupied binding sites. Instead, the standard
      KinExA assay quantifies the fraction of total antibody binding sites that are
      unoccupied, regardless of the number of unoccupied sites on each antibody
      molecule. Although the standard KinExA analysis assumes that there is only a
      small probability of antibody-site capture by the affinity matrix, the results of
      numerical simulations demonstrate the reliability of dissociation constants
      obtained by the standard KinExA analysis for capture probabilities as high as
      30%. This finding further strengthens the potential of kinetic exclusion assays
      as the procedure of choice for the rapid and accurate characterization of
      immunochemical reactions that forms part of screening processes in the search for
      therapeutic antibodies. 

PMID- 24751467
TI  - Highly selective screening of the bioactive compounds in Huoxue capsule using
      immobilized beta(2)-adrenoceptor affinity chromatography.
AB  - A highly selective assay was developed for screening compounds that bind to the
      porcine recombinant beta2-adrenoceptor (beta2-AR) with affinity chromatography
      coupled to quadrupole time-of-flight mass spectrometry (Q-TOF-MS). The
      methodology involved selective screening with immobilized beta2-AR, a highly
      accurate identification via Q-TOF-MS, and a functional evaluation of the screened
      compounds with a sensitive myograph system. Ferulic acid, hydroxysafflor yellow A
      (HSYA), and naringin were confirmed to be the bioactive compounds in Huoxue
      capsule that specifically bound to the beta2-AR. These compounds produced a
      concentration-dependent relaxation of arteries that were contracted by treatment
      with phenylephrine, and the relaxation caused by these compounds was attenuated
      in the presence of ICI 118551, a type of beta2-AR antagonist. Our data indicate
      that the use of an immobilized receptor is potentially an alternative method for
      the rapid screening of bioactive compounds in a complex matrix because of its
      high specificity. beta2-AR affinity chromatography was valuable in focusing
      attention on the further investigation of ferulic acid, HSYA, and naringin as
      beta2-AR agonists. 

PMID- 24751469
TI  - Real-time single-molecule observations of T7 Exonuclease activity in a microflow
      channel.
AB  - T7 Exonuclease (T7 Exo) DNA digestion reactions were studied using direct single
      molecule observations in microflow channels. DNA digestion reactions were
      directly observed by staining template DNA double-stranded regions with SYTOX
      Orange and staining single-stranded (digested) regions with a fluorescently
      labeled ssDNA-recognizing peptide (ssBP-488). Sequentially acquired photographs
      demonstrated that a double-stranded region monotonously shortened as a single
      stranded region monotonously increased from the free end during a DNA digestion
      reaction. Furthermore, DNA digestion reactions were directly observed both under
      pulse-chase conditions and under continuous buffer flow conditions with T7 Exo.
      Under pulse-chase conditions, the double-stranded regions of lambdaDNA
      monotonously shortened by a DNA digestion reaction with a single T7 Exo molecule,
      with an estimated average DNA digestion rate of 5.7 bases/s and a processivity of
      6692 bases. Under continuous buffer flow conditions with T7 Exo, some pauses were
      observed during a DNA digestion reaction and double-stranded regions shortened
      linearly except during these pauses. The average DNA digestion rate was estimated
      to be 5.3 bases/s with a processivity of 5072 bases. Thus, the use of our direct
      single-molecule observations using a fluorescently labeled ssDNA-recognizing
      peptide (ssBP-488) was an effective analytic method for investigating DNA
      metabolic processes.

PMID- 24751470
TI  - Effect of oxandrolone and timing of oral ethinylestradiol initiation on pubertal
      progression, height velocity and bone maturation in the UK Turner study.
AB  - BACKGROUND: A UK study showed final height in Turner syndrome (TS) girls
      receiving growth hormone is affected by age at pubertal induction and oxandrolone
      (Ox). Using data from that study, we analysed the effect of timing of oral
      ethinylestradiol (EE2) and Ox on height velocity (HV), bone maturation and
      pubertal progression, and compared growth response in EE2-treated versus
      spontaneous puberty. METHODS: Analysis of HV, bone age and pubertal stage in 92
      TS girls (7-13 years) randomised to Ox (0.05 mg/kg/day; max: 2.5 mg/day) or
      placebo from 9 years, and EE2 (year 1: 2 ug/day; year 2: 4 ug/day; year 3: 6/8/10
      ug/day*4 months) or placebo at 12 years with EE2 at 14 years. Girls enrolled at
      >12.25 years received EE2 at 14 years ('late group'). RESULTS: Fifty-six girls
      were randomised to EE2 at 12 years (n=28, 11 Ox) or 14 years (n=28, 13 Ox); there
      were 19 girls in the late group (9 Ox) and 17 girls with spontaneous puberty (10
      Ox). Girls receiving EE2 at 12 versus 14 years had faster bone maturation, but
      neither group showed acceleration. Ox increased HV without altering bone
      maturation or pubertal progression. Girls with spontaneous puberty had greater
      pubertal growth (mean PHV 8.5 cm/year; p<0.001) and height gain (p<0.001) than
      EE2-treated girls despite similar mean enrolment height SD and dysmorphology
      scores. CONCLUSION: Pubertal induction with EE2 does not replicate the
      acceleration observed in unaffected girls or TS girls with spontaneous puberty.

PMID- 24751471
TI  - Distal interphalangeal joint bony dimensions related to headless compression
      screw sizes.
AB  - PURPOSE: To determine the radiographic dimensions of the distal interphalangeal
      (DIP) joint and to compare these measurements with commonly used headless
      compression screws. METHODS: Using standard posteroanterior and lateral
      radiographs of the hand, we measured the dimensions of the distal and middle
      phalanges in 60 index, middle, ring, and little fingers. We then compared these
      measurements with the diameters and lengths of 16 commercially available headless
      compression screws commonly used to perform DIP joint arthrodesis. Percent
      compatibility and risk factors for incompatibility were determined. RESULTS: In
      general, commercially available screw diameters were too large given the anatomic
      dimensions of the DIP joint. The distal phalanx shaft as measured on the lateral
      view was the narrowest determinant of fit. When the dimensions of all fixation
      devices were combined, screws were oversized relative to the bony anatomy in 66%
      of index fingers, 53% of middle fingers, 49% of ring fingers, and 72% of little
      fingers. This mismatch was greater in women than in men. Only 1 of the
      compression screw types demonstrated a compatibility rate greater than 90% for
      the index and little fingers, respectively. A multivariate analysis of
      independent risk factors showed the likelihood of a compatible fit to vary
      directly with patient height and to be less likely in the little and index
      fingers. Interobserver reliability analysis revealed excellent x-ray measurement
      correlation between observers. CONCLUSIONS: A size mismatch existed between the
      anatomic dimensions of the DIP joint and commercially available headless
      compression screws. Caution must be used when considering these screws for DIP
      joint arthrodesis, to avoid problems related to screw prominence in the narrow
      aspects of the distal and middle phalanges. CLINICAL RELEVANCE: Headless
      compression screws are frequently oversized for use in DIP arthrodesis.

PMID- 24751472
TI  - Chronic granulomatous dermatosis as a presenting sign of a lymphoepithelioid T
      cell lymphoma (Lennert lymphoma).

PMID- 24751473
TI  - Assessment of the acute effects of different PEP levels on respiratory pattern
      and operational volumes in patients with Parkinson's disease.
AB  - The aim of the study was to determine the acute effects of positive expiratory
      pressure (PEP) on breathing pattern, operational volumes and shortening velocity
      of respiratory muscles on patients with Parkinson's disease. It was evaluated 15
      patients and healthy controls, by optoelectronic plethysmography, using PEP in
      three different levels (10, 15 and 20cmH2O). Breathing pattern changed in both
      groups. Parkinson group increased tidal volume in all PEP levels (p<0.001), but
      with lower values compared to control. End-inspiratory chest wall volume
      increased in the Parkinson group at all PEP levels (p<0.001), end-expiratory
      chest wall volume show a slightly increase when we compared QB to all PEP levels
      in Parkinson's. There was an intergroup difference in the index of shortening
      velocity of abdominal, diaphragm and inspiratory muscles of the rib cage at all
      PEP levels (p<0.01). We conclude that Parkinson's disease promotes important
      alterations in different breathing pattern components and PEP has significant
      effects on these alterations. 

PMID- 24751474
TI  - Platelet/lymphocyte ratio and risk of in-hospital mortality in patients with ST
      elevated myocardial infarction.
AB  - BACKGROUND: Platelet-to-lymphocyte ratio (PLR) is a new prognostic marker in
      coronary artery disease. We aimed to evaluate the relationship between PLR and in
      hospital mortality in patients with ST-elevated acute myocardial infarction
      (AMI). MATERIAL AND METHODS: The present study included 636 patients with ST
      elevated AMI. The study population was divided into tertiles based on their
      admission PLR. Patients having values in the third tertile was defined as the
      high PLR group (n=212) and those having values in the lower 2 tertiles were
      defined as the low PLR group (n=424). RESULTS: Risk factors of coronary artery
      disease and treatments administered during the in-hospital period were similar
      between the groups. Male patient ratio was found to be lower in the high PLR
      group (73% vs. 82.8%, p=0.004). In-hospital mortality was increased in the high
      PLR group when compared to the low PLR group (12.7% vs. 5.9%, p=0.004). The PLR
      >144 was found to be an independent predictor of in-hospital cardiovascular
      mortality (HR: 2.16, 95% CI: 1.16-4.0, p=0.014). CONCLUSIONS: This study showed
      that PLR is an independent predictor of cardiovascular mortality in patients with
      ST-elevated AMI.

PMID- 24751475
TI  - Second order sliding mode control for a quadrotor UAV.
AB  - A method based on second order sliding mode control (2-SMC) is proposed to design
      controllers for a small quadrotor UAV. For the switching sliding manifold design,
      the selection of the coefficients of the switching sliding manifold is in general
      a sophisticated issue because the coefficients are nonlinear. In this work, in
      order to perform the position and attitude tracking control of the quadrotor
      perfectly, the dynamical model of the quadrotor is divided into two subsystems,
      i.e., a fully actuated subsystem and an underactuated subsystem. For the former,
      a sliding manifold is defined by combining the position and velocity tracking
      errors of one state variable, i.e., the sliding manifold has two coefficients.
      For the latter, a sliding manifold is constructed via a linear combination of
      position and velocity tracking errors of two state variables, i.e., the sliding
      manifold has four coefficients. In order to further obtain the nonlinear
      coefficients of the sliding manifold, Hurwitz stability analysis is used to the
      solving process. In addition, the flight controllers are derived by using
      Lyapunov theory, which guarantees that all system state trajectories reach and
      stay on the sliding surfaces. Extensive simulation results are given to
      illustrate the effectiveness of the proposed control method. 

PMID- 24751476
TI  - Robust fault-tolerant tracking control design for spacecraft under control input
      saturation.
AB  - In this paper, a continuous globally stable tracking control algorithm is
      proposed for a spacecraft in the presence of unknown actuator failure, control
      input saturation, uncertainty in inertial matrix and external disturbances. The
      design method is based on variable structure control and has the following
      properties: (1) fast and accurate response in the presence of bounded
      disturbances; (2) robust to the partial loss of actuator effectiveness; (3)
      explicit consideration of control input saturation; and (4) robust to uncertainty
      in inertial matrix. In contrast to traditional fault-tolerant control methods,
      the proposed controller does not require knowledge of the actuator faults and is
      implemented without explicit fault detection and isolation processes. In the
      proposed controller a single parameter is adjusted dynamically in such a way that
      it is possible to prove that both attitude and angular velocity errors will tend
      to zero asymptotically. The stability proof is based on a Lyapunov analysis and
      the properties of the singularity free quaternion representation of spacecraft
      dynamics. Results of numerical simulations state that the proposed controller is
      successful in achieving high attitude performance in the presence of external
      disturbances, actuator failures, and control input saturation. 

PMID- 24751477
TI  - Plasma pentraxin-3 and coagulation and fibrinolysis variables during acute
      Puumala hantavirus infection and associated thrombocytopenia.
AB  - Thrombocytopenia and altered coagulation characterize all hantavirus infections.
      To further assess the newly discovered predictive biomarkers of disease severity
      during acute Puumala virus (PUUV) infection, we studied the associations between
      them and the variables reflecting coagulation, fibrinolysis and endothelial
      activation. Nineteen hospital-treated patients with serologically confirmed acute
      PUUV infection were included. Acutely, plasma levels of pentraxin-3 (PTX3), cell
      free DNA (cf-DNA), complement components SC5b-9 and C3 and interleukin-6 (IL-6)
      were recorded as well as platelet ligands and markers of coagulation and
      fibrinolysis. High values of plasma PTX3 associated with thrombin formation
      (prothrombin fragments F1+2; r = 0.46, P = 0.05), consumption of platelet ligand
      fibrinogen (r = -0.70, P < 0.001) and natural anticoagulants antithrombin (AT) (r
      = -0.74, P < 0.001), protein C (r = -0.77, P < 0.001) and protein S free antigen
      (r = -0.81, P < 0.001) and a decreased endothelial marker ADAMTS13 (a disintegrin
      and metalloproteinase with a thrombospondin type 1 domain 13) (r = -0.48, P =
      0.04). Plasma level of AT associated with C3 (r = 0.76, P < 0.001), IL-6 (r = 
      0.56, P = 0.01) and cf-DNA (r = -0.47, P = 0.04). High cf-DNA coincided with
      increased prothrombin fragments F1+2 (r = 0.47, P = 0.04). Low C3 levels
      reflecting the activation of complement system through the alternative route
      predicted loss of all natural anticoagulants (for protein C r = 0.53, P = 0.03
      and for protein S free antigen r = 0.64, P = 0.004). Variables depicting altered
      coagulation follow the new predictive biomarkers of disease severity, especially
      PTX3, in acute PUUV infection. The findings are consistent with the previous
      observations of these biomarkers also being predictive for low platelet count and
      underline the cross-talk of inflammation and coagulation systems in acute PUUV
      infection.

PMID- 24751479
TI  - Continuous positive airway pressure in cardiovascular medicine: the underlying
      physiology is frequently unknown.

PMID- 24751478
TI  - Chlamydia psittaci inclusion membrane protein IncB associates with host protein
      Snapin.
AB  - Chlamydia (C.) psittaci, the causative agent of psittacosis in birds and humans,
      is the most important zoonotic pathogen of the family Chlamydiaceae. During a
      unique developmental cycle of this obligate intracellular pathogen, the
      infectious elementary body gains access to the susceptible host cell, where it
      transforms into the replicative reticulate body. C. psittaci uses dynein motor
      proteins for optimal early development. Chlamydial proteins that mediate this
      process are unknown. Two-hybrid screening with the C. psittaci inclusion protein
      IncB as bait against a HeLa Yeast Two-hybrid (YTH) library revealed that the host
      protein Snapin interacts with IncB. Snapin is a cytoplasmic protein that plays a
      multivalent role in intracellular trafficking. Confocal fluorescence microscopy
      using an IncB-specific antibody demonstrated that IncB, Snapin, and dynein were
      co-localized near the inclusion of C. psittaci-infected HEp-2 cells. This co
      localization was lost when Snapin was depleted by RNAi. The interaction of Snapin
      with both IncB and dynein has been shown in vitro and in vivo. We propose that
      Snapin connects chlamydial inclusions with the microtubule network by interacting
      with both IncB and dynein. 

PMID- 24751481
TI  - APC/C is an essential regulator of centrosome clustering.
AB  - Centrosome amplification has been extensively associated with cancer. Cancer
      cells with extra centrosomes have the ability to cluster the extra centrosomes
      and divide in a bipolar fashion. Although a number of proteins have been shown to
      be involved in centrosome clustering, a mechanistic understanding of how this
      process is coordinated is not yet well defined. Here, to reveal regulators of
      centrosome clustering, we perform small interfering RNA (siRNA) screens with
      multiple assay readouts in a human isogenic cellular model. We find that APC/C
      activity is essential for centrosome clustering. We show that the motor kinesin
      Eg5 is a substrate of APC/C-CDH1, and that inhibition of APC/C results in
      stabilization of Eg5. Increased Eg5 protein levels disturb the balance of forces
      on the spindle and prevent centrosome clustering. This process is completely
      reversed after a short treatment with the Eg5 inhibitor, monastrol. These data
      advance our understanding of the regulation of centrosome clustering. 

PMID- 24751480
TI  - C-reactive protein and subclinical cardiovascular disease among African
      Americans: (the Jackson Heart Study).
AB  - OBJECTIVE: Systemic inflammation has been implicated as an early marker for
      subclinical cardiovascular disease; however, findings have been inconsistent in
      the African-American population. METHODS: We examined the relation of C-reactive
      protein (CRP) to subclinical disease in African-American participants of the
      Jackson Heart Study first examination. Subclinical disease evaluated included
      aortic valve calcification (AVC), carotid intima-medial thickness (IMT) and
      peripheral arterial disease (PAD). We assessed the relation of CRP to subclinical
      disease, adjusting for age, BMI, sex, SBP and DBP, diabetes, total/high-density
      lipoprotein cholesterol, triglycerides, smoking, antihypertensive therapy, lipid
      lowering therapy and hormone replacement therapy. RESULTS: In the study
      population approximately, 5.1% of participants had AVC and 6.7% had PAD. In the
      age-adjusted and sex-adjusted model, CRP was significantly related to AVC (P =
      0.02) and carotid IMT (P = 0.02). However, in the multivariable-adjusted logistic
      regression analysis, CRP was significantly related to AVC (P = 0.02) and to PAD
      (P = 0.04) but not to carotid IMT (P = 0.18). CONCLUSION: We describe significant
      associations between CRP and AVC and PAD in a population-based cohort of African
      Americans.

PMID- 24751482
TI  - Pre- and intra-operative variables associated with surgical complications in
      elderly patients with gynecologic cancer: the clinical value of comprehensive
      geriatric assessment.
AB  - OBJECTIVE: The aim of this study is to evaluate the associations of pre- and
      intra-operative variables including comprehensive geriatric assessment (CGA) with
      surgical complications in elderly patients who underwent primary surgery for
      gynecologic cancer. METHODS: Sixty consecutive patients >=70years of age who were
      scheduled to undergo elective surgery for the treatment of gynecologic cancer
      were preoperatively assessed by CGA. Every category of CGA, performance status
      (PS), and brief fatigue inventory (BFI) as well as surgical complexity were
      evaluated for 30-day surgical complications. RESULTS: The overall postoperative
      complication rate was 30.0% (18/60) including 9 (15.0%) major and 8 (13.3%)
      multiple complications. Univariate analysis revealed that dependent instrumental
      activity of daily living (IADL) was associated with any (p=0.023) and multiple
      complications (p=0.019). Poor PS was associated with major (p=0.021) and multiple
      complications (p=0.014). Multivariate logistic regression analysis revealed that
      high surgical complexity was the most independent predictor of any, major, and
      multiple complications, whereas poor PS was the independent predictor only for
      multiple complications (odds ratio 10.7, 95% confidence interval 1.7 to 90.2,
      p=0.043). There was no CGA component which could independently predict
      postoperative complications. CONCLUSION: Surgical complexity can predict any,
      major, and multiple postoperative complications, while PS seems to be useful in
      predicting multiple complications in elderly patients with gynecologic cancer. In
      this small study, a CGA was not useful in predicting postoperative complications.

PMID- 24751483
TI  - SIRT1 deacetylase is overexpressed in human melanoma and its small molecule
      inhibition imparts anti-proliferative response via p53 activation.
AB  - Melanoma causes more deaths than any other skin cancer, and its incidence in the
      US continues to rise. Current medical therapies are insufficient to control this
      deadly neoplasm, necessitating the development of new target-based approaches.
      The objective of this study was to determine the role and functional significance
      of the class III histone deacetylase SIRT1 in melanoma. We have found that SIRT1
      is overexpressed in clinical human melanoma tissues and human melanoma cell lines
      (Sk-Mel-2, WM35, G361, A375, and Hs294T) compared to normal skin and normal
      melanocytes, respectively. In addition, treatment of melanoma cell lines A375,
      Hs294T, and G361 with Tenovin-1, a small molecule SIRT1 inhibitor, resulted in a
      significant decrease in cell growth and cell viability. Further, Tenovin-1
      treatment also resulted in a marked decrease in the clonogenic survival of
      melanoma cells. Further experiments showed that the anti-proliferative response
      of Tenovin-1 was accompanied by an increase in the protein as well as activity of
      the tumor suppressor p53. This increase in p53 activity was substantiated by an
      increase in the protein level of its downstream target p21. Overall, these data
      suggest that small molecule inhibition of SIRT1 causes anti-proliferative effects
      in melanoma cells. SIRT1 appears to be acting through the activity of the tumor
      suppressor p53, which is not mutated in the majority of melanomas. However,
      future detailed studies are needed to further explore the role and mechanism of
      SIRT1 in melanoma development and progression and its usefulness in melanoma
      treatment.

PMID- 24751484
TI  - Acetylation of acetyl-CoA synthetase from Mycobacterium tuberculosis leads to
      specific inactivation of the adenylation reaction.
AB  - Acetyl-CoA synthetase (ACS) catalyzes the formation of AcCoA from acetate, ATP
      and Coenzyme A, allowing the organism to grow on acetate as the sole carbon
      source. ACS was the first enzyme in Mycobacterium tuberculosis shown to be
      regulated by posttranslational acetylation by the cAMP-dependent protein
      acetyltransferase. This modification results in the inactivation of the enzyme
      and can be reversed in the presence of NAD(+) and a mycobacterial sirtuin-like
      deacetylase. In this study we characterize the kinetic mechanism of MtACS, where
      the overall reaction can be divided into two half-reactions: the acetyl-adenylate
      forming reaction and the thiol-ligation reaction. We also provide evidence for
      the existence of the acetyl-adenylate intermediate via (31)P NMR spectroscopy.
      Furthermore, we dissect the regulatory role of K617 acetylation and show that
      acetylation inhibits only the first, adenylation half-reaction while leaving the
      second half reaction unchanged. Finally, we demonstrate that the chemical
      mechanism of the enzyme relies on a conformational change which is controlled by
      the protonation state of aspartate 525. Together with our earlier results, this
      suggests a degree of regulation of enzyme activity that is appropriate for the
      role of the enzyme in central carbon metabolism. 

PMID- 24751485
TI  - Influence of recurrent electroconvulsive therapy on cardiac function.
AB  - OBJECTIVE: To investigate the effects of recurrent electroconvulsive therapy
      (ECT) on cardiac function as assessed by echocardiography. SUBJECTS AND METHODS:
      Twenty-three patients (11 males and 12 females) with different psychiatric
      disorders who were apparently free of any cardiovascular disorders and underwent
      ECT were enrolled in the study. Echocardiographic findings including diastolic
      mitral inflow and tissue Doppler features were recorded at baseline and at the
      end of the 7th and last ECT in all patients. RESULTS: The mean age of the
      patients was 37.95 +/- 13.28 years (range 19-71). There was no significant
      difference in mitral E wave velocities and tissue Doppler E' velocities between
      the baseline and after the 1st ECT (p = 0.161 and p = 0.083, respectively). The
      results were similar after the last ECT session (p = 0.463 and p = 0.310,
      respectively). However, there was a significant increase in transmitral A wave
      velocity after the 1st and 7th ECT session compared to the values at baseline (p
      = 0.008 and p = 0.017, respectively). CONCLUSION: The mitral diastolic inflow A
      wave velocity increased 20 min after ECT, and this increase persisted after
      recurrent ECT sessions. This finding could be considered as an indicator of
      acutely increased sympathetic tone.

PMID- 24751486
TI  - A personalized stereotactic fixture for implantation of depth electrodes in
      stereoelectroencephalography.
AB  - BACKGROUND: The stereoelectroencephalographic (SEEG) implantation procedures
      still represent a challenge due to the intrinsic complexity of the method and the
      number of depth electrodes required. OBJECTIVES: We aim at designing and
      evaluating the accuracy of a custom stereotactic fixture based on the StarFixTM
      technology (FHC Inc., Bowdoin, ME) that significantly simplifies and optimizes
      the implantation of depth electrodes used in presurgical evaluation of patients
      with drug-resistant epilepsy. METHODS: Fiducial markers that also serve as
      anchors for the fixture are implanted into the patient's skull prior to surgery.
      A 3D fixture model is designed within the surgical planning software, with the
      planned trajectories incorporated in its design, aligned with the patient's
      anatomy. The stereotactic fixture is built using 3D laser sintering technology
      based on the computer-generated model. Bilateral rectangular grids of guide holes
      orthogonal to the midsagittal plane and centered on the midcommissural point are
      incorporated in the fixture design, allowing a wide selection of orthogonal
      trajectories. Up to two additional grids can be accommodated for targeting
      structures where oblique trajectories are required. The frame has no adjustable
      parts, this feature reducing the risk of inaccurate coordinate settings while
      simultaneously reducing procedure time significantly. RESULTS: We have used the
      fixture for the implantation of depth electrodes for presurgical evaluation of 4
      patients with drug-resistant focal epilepsy, with nearly 2-fold reduction in the
      duration of the implantation procedure. We have obtained a high accuracy with a
      submillimetric mean positioning error of 0.68 mm for the anchor bolts placed at
      the trajectory entry point and 1.64 mm at target. CONCLUSIONS: The custom
      stereotactic fixture design greatly simplifies the planning procedure and
      significantly reduces the time in the operating room, while maintaining a high
      accuracy.

PMID- 24751487
TI  - Varicella zoster virus encephalopathy in a patient with psoriatic arthritis
      treated with anti-TNFalpha agents.

PMID- 24751488
TI  - Therapeutic hypothermia after in-hospital cardiac arrest: a critique.
AB  - More than 210,000 in-hospital cardiac arrests occur annually in the United
      States. Use of moderate therapeutic hypothermia (TH) in comatose survivors after
      return of spontaneous circulation following out-of-hospital cardiac arrest (OOH
      CA) caused by ventricular fibrillation or pulseless ventricular tachycardia is
      recommended strongly by many professional organizations and societies. The use of
      TH after cardiac arrest associated with nonshockable rhythms and after in
      hospital cardiac arrest (IH-CA) is recommended to be considered by these same
      organizations and is being applied widely. The use in these latter circumstances
      is based on an extrapolation of the data supporting its use after out-of-hospital
      cardiac arrest associated with shockable rhythms. The purpose of this article is
      to review the limitations of existing data supporting these extended application
      of TH after cardiac arrest and to suggest approaches to this dilemma. The data
      supporting its use for OOH-CA appear to this author, and to some others, to be
      rather weak, and the data supporting the use of TH for IH-CA appear to be even
      weaker and to include no randomized controlled trials (RCTs) or supportive
      observational studies. The many reasons why TH might be expected to be less
      effective following IH-CA are reviewed. The degree of neurologic injury may be
      more severe in many of these cases and, thus, may not be responsive to TH as
      currently practiced following OOH-CA. The potential adverse consequences of the
      routine use of TH for IH-CA are listed and include complications associated with
      TH, interference with diagnostic and interventional therapy, and use of scarce
      personnel and financial resources. Most importantly, it inhibits the ability of
      researchers to conduct needed RCTs. The author believes that the proper method of
      providing TH in these cases needs to be better defined. Based on this analysis
      the author concludes that TH should not be used indiscriminantly following most
      cases of IH-CA, and instead clinicians should concentrate their efforts in
      conducting high-quality large RCTs or large-scale, well-designed prospective
      observation studies to determine its benefits and identify appropriate
      candidates. 

PMID- 24751489
TI  - Short-term effects of Dechlorane Plus on the earthworm Eisenia fetida determined
      by a systems biology approach.
AB  - Dechlorane Plus (DP), a chlorinated flame retardant, has been widely detected in
      environmental matrices, especially in sediment and soil. DP has characteristics
      similar to persistent organic pollutants. However, no toxicity data of DP on
      terrestrial invertebrate are available. In this study, earthworms Eisenia fetida
      were exposed to 0.1, 1, 10, and 50mg/kg DP for 14 days. Lethality, oxidative
      stress and damage, neurotoxicity, and transcriptomic profiles of E. fetida were
      assessed on day 7 and day 14 of exposure. Results showed that the acute toxicity
      of DP was very low. However, DP exposure induced an increase in the oxidative
      stress markers malonaldehyde (MDA) and 8-Hydroxy-2'-deoxyguanosine (8-OHdG), and
      altered acetylcholinesterase (AChE) activities. High throughput sequencing-based
      transcriptomic analysis showed that DP exposure significantly altered gene
      expression and pathways related to antioxidant enzymes, stress responses,
      neurological dysfunctions, calcium binding, and signal transduction. The results
      from different toxicological endpoints indicate that DP toxicity on the earthworm
      is primarily through oxidative damage and neurotoxicity. Based on these results,
      we deduce that changes in oxidative stress and neurotoxicity might be the primary
      mechanisms of DP toxicity. This study provides insight into the toxicological
      effects of DP on earthworm model, and may be useful for risk assessment of DP on
      soil ecosystems. 

PMID- 24751490
TI  - In situ stabilization of As and Sb with naturally occurring Mn, Al and Fe oxides
      in a calcareous soil: bioaccessibility, bioavailability and speciation studies.
AB  - This study investigated the effectiveness of 6 different types of naturally
      occurring manganese, aluminum and iron oxides for stabilization of As and Sb in a
      calcareous soil spiked with 50mgkg(-1) of As or Sb and two dosages of treatments
      (2% and 5%). The resulting contaminated soils were subjected to a series of
      chemical extraction studies including sequential extraction, single step
      extraction with DTPA and Simplified Bioaccessibility Extraction Test (SBET) for
      estimation of bioaccessible fraction of As and Sb in soil and a greenhouse
      experiment using barley as the test crop. The results showed that Fe-associated
      and carbonate-bound fraction of As and Sb were predominant fractions. However,
      the amounts of labile fractions were higher in As contaminated soils, whereas the
      percentage of Sb associated with crystalline Fe-oxide and residual fractions were
      higher. The results revealed that application of natural metal oxides reduced
      DTPA and SBET extractable amounts and plant uptake of As and Sb. After
      application of amendments, the exchangeable fraction of As decreased dramatically
      by up to 82% while Sb exchangeable fraction decreased by up to 60% depending upon
      the additive. The results of chemical extractions and plant uptake confirmed that
      Sb had lower bioavailability, compared with As. 

PMID- 24751491
TI  - Cr(VI) transport via a supported ionic liquid membrane containing CYPHOS IL101 as
      carrier: system analysis and optimization through experimental design strategies.
AB  - Chromium(VI) transport through a supported liquid membrane (SLM) system
      containing the commercial ionic liquid CYPHOS IL101 as carrier was studied. A
      reducing stripping phase was used as a mean to increase recovery and to
      simultaneously transform Cr(VI) into a less toxic residue for disposal or reuse.
      General functions which describe the time-depending evolution of the metal
      fractions in the cell compartments were defined and used in data evaluation. An
      experimental design strategy, using factorial and central-composite design
      matrices, was applied to assess the influence of the extractant, NaOH and citrate
      concentrations in the different phases, while a desirability function scheme
      allowed the synchronized optimization of depletion and recovery of the analyte.
      The mechanism for chromium permeation was analyzed and discussed to contribute to
      the understanding of the transfer process. The influence of metal concentration
      was evaluated as well. The presence of different interfering ions (Ca(2+),
      Al(3+), NO3(-), SO4(2-), and Cl(-)) at several Cr(VI): interfering ion ratios was
      studied through the use of a Plackett and Burman experimental design matrix.
      Under optimized conditions 90% of recovery was obtained from a feed solution
      containing 7mgL(-1) of Cr(VI) in 0.01moldm(-3) HCl medium after 5h of
      pertraction. 

PMID- 24751492
TI  - Adsorption of methylene blue onto poly(cyclotriphosphazene-co-4,4'
      sulfonyldiphenol) nanotubes: kinetics, isotherm and thermodynamics analysis.
AB  - Poly(cyclotriphosphazene-co-4,4'-sulfonyldiphenol) (PZS) nanotubes, an excellent
      adsorbent, were successfully synthesized by an in situ template method and used
      for the removal of methylene blue (MB) from aqueous solution. The morphology and
      structures of as-synthesized PZS nanotubes were characterized by scanning
      electron microscopy, transmission electron microscope, Fourier transform infrared
      spectroscopy and N2 adsorption/desorption isotherms. The effects of temperature,
      concentration, pH and contact time on MB adsorption were studied. It was
      favorable for adsorption under the condition of basic and high temperature. The
      pseudo-first-order, pseudo-second-order and intraparticle diffusion models were
      used to fit adsorption data in the kinetic studies. And results showed that the
      adsorption kinetics were more accurately described by the pseudo-second-order
      model. The equilibrium isotherms were conducted using Freundlich and Langmuir
      models. It has been demonstrated that the better agreement was Langmuir isotherm
      with correlation coefficient of 0.9933, equilibrium absorption capacity of
      69.16mg/g and the corresponding contact time of 15min. Thermodynamic analyses
      showed that MB adsorption onto the PZS nanotubes was endothermic and spontaneous
      and it was also a physisorption process. 

PMID- 24751493
TI  - Effect of aging on arsenic and lead fractionation and availability in soils:
      coupling sequential extractions with diffusive gradients in thin-films technique.
AB  - We coupled the diffusive gradients in thin-films (DGT) technique with two
      sequential extraction methods to investigate the influence of aging on As and Pb
      fractionation and availability in three soils spiked with As (40 or 400mgkg(-1)),
      Pb (150 or 1500mgkg(-1)) or As+Pb (40mgkg(-1) As and 150mgkg(-1) Pb). During
      aging, As moved from the more available (non-specifically and specifically
      sorbed) to less available (amorphous and crystallized Fe/Al) fractions while Pb
      moved from the first three fractions (exchangeable, carbonate and Fe/Mn
      hydroxide) to organic fraction. However, even after 33-week aging, much more As
      and Pb were in the least available residual fraction in spiked soils than native
      soils (11-59% vs. 1.2-12%). Relatively, As in spiked soils was much more
      available than Pb with 11-14% As and 46-59% Pb in the residual fraction.
      Correlation analysis indicated that As in the non-specifically and specifically
      sorbed fractions and Pb in the exchangeable fraction were likely sources of DGT
      measured labile As and Pb. The fact that As and Pb distribution and availability
      in spiked soils were significantly different from native soils suggests caution
      needs to be exercised when using spiked soils for research. 

PMID- 24751494
TI  - Antiestrogenic activity and related disinfection by-product formation induced by
      bromide during chlorine disinfection of sewage secondary effluent.
AB  - Chlorine disinfection, widely used in wastewater reclamation, can form toxic and
      harmful disinfection by-products (DBPs), some of which are associated with
      endocrine disruption. In this study, the presence of bromide was found to promote
      an increase in antiestrogenic activity using a yeast two-hybrid assay in the
      sewage secondary effluent during chlorine disinfection. Among the dissolved
      organic matters in the secondary effluent, hydrophobic acids and hydrophilic
      substance fractions were determined as potential precursors associated with
      increase in antiestrogenic activity in the secondary effluent induced by bromide.
      Further antiestrogenic activity evaluation and mass spectrum characterization
      following the semipreparative liquid chromatography fractionation of a natural
      organic matter precursor, tyrosine, after chlorination under the presence of
      bromide revealed, for the first time, that 2-(bromo-4-hydroxyphenyl) acetonitrile
      (Br-HPAN) and 2-(dibromo-4-hydroxyphenyl) acetonitrile (DBr-HPAN) exhibited
      antiestrogenic activity. Br-HPAN and DBr-HPAN were the DBPs involved in the
      increase in antiestrogenic activity in the tyrosine solution. Bromide was shown
      to induce the formation of Br-HPAN and DBr-HPAN in the secondary effluent during
      chlorine disinfection. 

PMID- 24751495
TI  - Characterization of novel intergenogroup and intergenotype recombinant
      noroviruses from central Greece.
AB  - Noroviruses (NoVs) are a major causative agent of acute gastroenteritis in
      humans. They are members of the Caliciviridae family and based on the genetic
      analysis of the RdRp and capsid regions, human NoVs are divided into three
      genogroups (Gs), GI, GII, and GIV. The three genogroups further segregate into
      distinct lineages called genotypes. The NoV genus is genetically diverse and
      recombination of viral RNA is known to depend upon various immunological and
      intracellular constraints that may allow the emergence of viable recombinants. In
      this study, three Noroviral strains detected in clinical samples revealed two
      hitherto unobserved recombination events between GII.9/GII.4 and GII.9/GI.7
      genogroups. To our knowledge, these intergenotype and intergenogroup
      recombination events of GII.9/GII.4 and GII.9/GI.7, in ORF1 and ORF2 genes
      respectively are reported for the first time and highlight the ongoing evolution
      of noroviruses.

PMID- 24751496
TI  - Individual course of cranial symmetry and proportion in preterm infants up to 6
      months of corrected age.
AB  - INTRODUCTION: A significant proportion of preterm infants have dolichocephaly
      and/or deformational plagiocephaly (DP) at term equivalent age. However,
      quantitative data on the clinical course after discharge is limited in these
      infants. AIMS: To quantify the individual course of cranial symmetry and
      proportion in infants born <32 gestational weeks up to six months of corrected
      age (CA) and to investigate, whether measurements at discharge predict subsequent
      cranial deformations. METHODS: A total of 56 infants were examined at discharge,
      three and six months of CA. Cranial proportion and symmetry were quantified using
      a 3D laser scan method. Classification and prevalence data were obtained using
      age related reference values. Predictive value of DP at discharge regarding
      subsequent deformation was evaluated. RESULTS: Cranial Vault Asymmetry Index was
      3.9% at discharge, 4.5% at three months and 3.7% at six months of CA. Prevalence
      of DP was 34% at discharge, 46% at three months and 27% at six months. Cranial
      Index was 71.4% at discharge and constantly increased over the examination
      period. Prevalence of dolichocephaly was high at discharge (77%) and subsequently
      decreased. While severe DP at discharge was predictive for a persistent
      deformation (PPV 0.78), 46% of infants without DP at discharge developed DP by
      six months of CA. DISCUSSION: Despite a high prevalence at discharge, the
      decreased prevalence of DP and dolichocephaly at six months of CA suggests an
      optimistic course. However, changes in head shape are hardly predictable for the
      individual infant. Thus, an accurate quantification should be part of neonatal
      follow-up programs.

PMID- 24751497
TI  - Identifying critically ill patients at risk for inappropriate antibiotic therapy:
      a pilot study of a point-of-care decision support alert.
AB  - OBJECTIVE: To develop an automated alert aimed at reducing inappropriate
      antibiotic therapy of serious healthcare-associated infections. DESIGN: Single
      center cohort study from November 2011 to November 2012. SETTING: Barnes-Jewish
      Hospital (1,250-bed academic hospital). PATIENTS: A total of 3,616 critically ill
      patients receiving treatment with antibiotics targeting healthcare-associated
      infections due to Gram-negative bacteria. INTERVENTIONS: Upon antibiotic order
      entry in the ICU for a Gram-negative antibiotic, the antibiotic and microbiologic
      history for each patient was electronically queried in real time across all 13
      BJC HealthCare hospitals. Patients were assigned to the alert group if they had
      exposure to the same antibiotic class currently being prescribed (cefepime,
      meropenem, or piperacillin-tazobactam) or had a positive culture isolating a Gram
      negative organism with resistance to the prescribed antibiotic in the previous 6
      months. MEASUREMENTS AND MAIN RESULTS: Nine hundred patients (24.2%) generated an
      alert. Alerted patients were significantly more likely to receive inappropriate
      antibiotic therapy (7.1% vs. 2.9%; p < 0.001). Based on clinical information
      available in the alert, 34 of 64 of the alerted patients that received
      inappropriate therapy (53.1%) could have received an alternative beta-lactam
      antibiotic with in vitro susceptibility to the identified pathogen. Independent
      predictors (adjusted odds ratio [95% CI]) of inappropriate therapy included alert
      generation (1.788 [1.167-2.740]; p = 0.008), medical ICU patients (1.528 [1.007
      2.319]; p = 0.046), and a pulmonary source of infection (2.063 [1.363-3.122]; p =
      0.0001). Patients in the alert group had significantly greater hospital mortality
      (29.9% vs. 23.6%; p < 0.001) and hospital length of stay (median, 13.1 vs. 10.7
      d; p < 0.001) compared with nonalert patients. CONCLUSIONS: Our results suggest
      that a simple automated alert could identify more than 40% of critically ill
      patients prescribed inappropriate antibiotic therapy for healthcare-associated
      infections. These data suggest that an opportunity exists to employ hospital
      informatics systems to improve the prescription of antibiotic therapy in ICU
      patients with suspected healthcare-associated infections.

PMID- 24751499
TI  - Managing age-related hearing loss: how to use hearing aids efficiently - a mini
      review.
AB  - Using hearing aids may contribute to better functioning in the everyday lives of
      hearing-impaired older individuals. We introduce an integrative concept for the
      efficient use of hearing aids that involves both satisfaction with, and behaviour
      towards, hearing aids. We review theoretical and empirical work on the predictors
      of the efficient use of hearing aids in everyday life. Furthermore, we contend
      that the use of hearing aids requires improved understanding of the variability
      of hearing demands within specific contexts of everyday life (e.g. conversation
      with family members, listening to music). The efficiency of hearing aid use thus
      depends on the fit of situational demands, personal resources, and the specific
      configuration of the hearing aid device. We propose an integrative person
      environment-fit model that advances concepts of selection, optimisation, and
      compensation to hearing aid efficiency. We discuss the implications of this model
      for research and for practitioners in the field of gerontology.

PMID- 24751498
TI  - Risk factors for ventilator-associated events: a case-control multivariable
      analysis.
AB  - OBJECTIVES: The Centers for Disease Control and Prevention recently released new
      surveillance definitions for ventilator-associated events, including the new
      entities of ventilator-associated conditions and infection-related ventilator
      associated complications. Both ventilator-associated conditions and infection
      related ventilator-associated complications are associated with prolonged
      mechanical ventilation and hospital death, but little is known about their risk
      factors and how best to prevent them. We sought to identify risk factors for
      ventilator-associated conditions and infection-related ventilator-associated
      complications. DESIGN: Retrospective case-control study. SETTING: Medical,
      surgical, cardiac, and neuroscience units of a tertiary care teaching hospital.
      PATIENTS: Hundred ten patients with ventilator-associated conditions matched to
      110 controls without ventilator-associated conditions on the basis of age, sex,
      ICU type, comorbidities, and duration of mechanical ventilation prior to
      ventilator-associated conditions. INTERVENTIONS: None. MEASUREMENTS: We compared
      cases with controls with regard to demographics, comorbidities, ventilator bundle
      adherence rates, sedative exposures, routes of nutrition, blood products, fluid
      balance, and modes of ventilatory support. We repeated the analysis for the
      subset of patients with infection-related ventilator-associated complications and
      their controls. MAIN RESULTS: Case and control patients were well matched on
      baseline characteristics. On multivariable logistic regression, significant risk
      factors for ventilator-associated conditions were mandatory modes of ventilation
      (odds ratio, 3.4; 95% CI, 1.6-8.0) and positive fluid balances (odds ratio, 1.2
      per L positive; 95% CI, 1.0-1.4). Possible risk factors for infection-related
      ventilator-associated complications were starting benzodiazepines prior to
      intubation (odds ratio, 5.0; 95% CI, 1.3-29), total opioid exposures (odds ratio,
      3.3 per 100 MUg fentanyl equivalent/kg; 95% CI, 0.90-16), and paralytic
      medications (odds ratio, 2.3; 95% CI, 0.79-80). Traditional ventilator bundle
      elements, including semirecumbent positioning, oral care with chlorhexidine,
      venous thromboembolism prophylaxis, stress ulcer prophylaxis, daily spontaneous
      breathing trials, and sedative interruptions, were not associated with ventilator
      associated conditions or infection-related ventilator-associated complications.
      CONCLUSIONS: Mandatory modes of ventilation and positive fluid balance are risk
      factors for ventilator-associated conditions. Benzodiazepines, opioids, and
      paralytic medications are possible risk factors for infection-related ventilator
      associated complications. Prospective studies are needed to determine if
      targeting these risk factors can lower ventilator-associated condition and
      infection-related ventilator-associated complication rates.

PMID- 24751500
TI  - Silicon carbide-derived carbon nanocomposite as a substitute for mercury in the
      catalytic hydrochlorination of acetylene.
AB  - Acetylene hydrochlorination is an important coal-based technology for the
      industrial production of vinyl chloride, however it is plagued by the toxicity of
      the mercury chloride catalyst. Therefore extensive efforts have been made to
      explore alternative catalysts with various metals. Here we report that a
      nanocomposite of nitrogen-doped carbon derived from silicon carbide activates
      acetylene directly for hydrochlorination in the absence of additional metal
      species. The catalyst delivers stable performance during a 150 hour test with
      acetylene conversion reaching 80% and vinyl chloride selectivity over 98% at 200 
      degrees C. Experimental studies and theoretical simulations reveal that the
      carbon atoms bonded with pyrrolic nitrogen atoms are the active sites. This proof
      of-concept study demonstrates that such a nanocomposite is a potential substitute
      for mercury while further work is still necessary to bring this to the industrial
      stage. Furthermore, the finding also provides guidance for design of carbon-based
      catalysts for activation of other alkynes.

PMID- 24751501
TI  - Photodynamic effects on human periodontal-related cells in vitro.
AB  - BACKGROUND: Photodynamic therapy (PDT) may be especially effective in combination
      with conventional periodontal therapy by its antimicrobial activities, but PDT
      may also exhibit other mechanisms that promote the healing of periodontal tissue.
      Therefore, the purpose of the present study was to evaluate the photodynamic
      effect of PDT on human periodontal ligament cells (hPDLCs) and human gingival
      fibroblasts (hFBs) in vitro and other possible mechanisms to promote periodontal
      healing. METHODS: The proliferation of hPDLCs and hFBs was assessed by MTT assay.
      Cell attachment on cementum slices of hPDLCs and hFBs was evaluated by MTT assay.
      Type I collagen synthesis of hPDLCs and hFBs was analyzed using enzyme linked
      immunosorbent assay. The alkaline phosphatase (ALP) activity in hPDLCs was
      measured by p-nitrophenyl phosphate substrate reactions. RESULTS: PDT treatment
      induced constant time-dependent growth of hPDLCs and hFBs at 24h, 72h and 6 days
      (P<0.05). PDT treatment also promoted time-dependent hPDLCs and hFBs attachment
      on the cementum slices at 24h, 72h and 6 days compared to the controlled cells
      (P<0.05). Type I collagen synthesis of hPDLCs and hFBs was markedly stimulated by
      PDT in a time-dependent manner (P<0.05). Likewise, a significant increase in the
      specific ALP activity in hPDLCs was observed (P<0.05). CONCLUSIONS: The findings
      of this study indicate that PDT exhibited no cytotoxicity to hPDLCs or hFBs.
      Instead, it stimulated proliferation, attachment and collagen synthesis of hPDLCs
      and hFBs and ALP activity of hPDLCs. These effects might signal similar PDT
      activity on periodontal-related cells, and expanding the scope of its potential
      therapeutic utilization is very appealing.

PMID- 24751502
TI  - Enhancement of myocardial function and reduction of injury with levosimendan
      after percutaneous coronary intervention for acute myocardial infarction: a pilot
      study.
AB  - OBJECTIVES: To determine the short-term clinical effects of levosimendan in acute
      myocardial infarction (AMI) patients with myocardial stunning after emergency
      percutaneous coronary intervention (PCI). METHODS: The study population consisted
      of 30 patients with AMI who received emergency PCI and satisfied the inclusion
      criteria. Levosimendan was given as a continuous infusion of 0.1 MUg/kg/min for
      24 h, and the remaining 10 patients received placebo treatment. The patients were
      observed with invasive haemodynamic monitoring and were evaluated biochemically
      and echocardiographically before and after the drug infusion. RESULTS: Following
      treatment, biochemical indices (not including creatine kinase and its MB
      fraction) were significantly lower in the levosimendan group than in the placebo
      group. Meanwhile, left-ventricular (LV) end-systolic volume, mean pulmonary
      arterial pressure, pulmonary capillary wedge pressure and systemic vascular
      resistance were significantly reduced in the levosimendan group, whereas the
      early-to-late diastolic velocities ratio, LV ejection fraction, cardiac index and
      cardiac power index were increased. Troponin I levels were reduced and fewer
      stunned and infarction segments were observed in the patients treated with
      levosimendan. CONCLUSIONS: Levosimendan can significantly improve the myocardium
      function of patients with myocardial stunning after PCI.

PMID- 24751503
TI  - Fulfilment of knowledge expectations and emotional state among people undergoing
      hip replacement: a multi-national survey.
AB  - BACKGROUND: Patient education in connection with hip replacement is intended to
      prepare patients for surgery, discharge and postoperative recovery. Patients
      experience symptoms and emotions due to disease or upcoming surgery which can
      affect how their knowledge expectations are fulfilled. OBJECTIVES: To describe
      the differences between received and expected knowledge in patients undergoing
      elective hip replacement in three Nordic countries, and to analyse how these
      differences are related to patients' characteristics, preoperative symptoms and
      emotions. DESIGN: A descriptive, prospective survey with two data collection
      points; before admission and at hospital discharge after surgery. SETTINGS: Two
      Finnish, three Icelandic and two Swedish hospitals. PARTICIPANTS: The population
      consisted of patients on a waiting list for hip replacement. Of the consecutively
      included patients, 320 answered questionnaires both before admission and at
      discharge and were included in the study. The mean age of the patients was 64
      years, and 55% were women. METHODS: Structured questionnaires were used; the
      knowledge expectations of hospital patients scale and self-reported scales for
      symptoms and emotions before admission and received knowledge of hospital
      patients scale at discharge. Fulfilment of knowledge expectation was assessed by
      calculating the difference between received and expected knowledge with a paired
      sample t-test. A multiple stepwise regression model was used to explain the
      variance of fulfilled knowledge expectations. RESULTS: Patients expected more
      knowledge than they received (p<0.001) and 77% of them had unfulfilled knowledge
      expectations. Patients with a higher level of education were more likely to have
      unfulfilled knowledge expectations. A higher level of education was also related
      to a greater difference between received and expected knowledge. The difference
      was more correlated with patients' emotions than their symptoms. A depressive
      state was the major predictor of the variance in the difference between received
      and expected knowledge. CONCLUSIONS: In order to better support patients by
      education it is necessary to assess their emotional state, educational level and
      knowledge expectations before surgery.

PMID- 24751504
TI  - The effect of molecular weight on the material properties of biosynthesized
      poly(4-hydroxybutyrate).
AB  - Poly(4-hydroxybutyrate) (P4HB) is a bacterial polyhydroxyalkanoate with
      interesting biological and physico-chemical properties for the use in biomedical
      applications. The synthesis of P4HB through a fermentation process often leads to
      a polymer with a too high molecular weight, making it difficult to process it
      further by solvent- or melt-processing. In this work P4HB was degraded to obtain
      polymers with a molecular weight ranging from 1.5*10(3)g/mol to 1.0*10(6)g/mol by
      using a method established in our laboratory. We studied the effect of the change
      in molecular weight on thermal and mechanical properties. The decrease of the
      molecular weight led to an increase in the degree of crystallinity of the
      polymer. Regarding the tensile mechanical properties, the molecular weight played
      a more prominent role than the degree of crystallinity in the evolution of the
      properties for the different polymer fractions. The method presented herein
      allows the preparation of polymer fractions with easier processability and still
      adequate thermal and mechanical properties for biomedical applications. 

PMID- 24751505
TI  - Cell system engineering to produce extracellular polyhydroxyalkanoate
      depolymerase with targeted applications.
AB  - Novel platforms based on the application of bacterial cell systems as factories
      for production of new bioproducts open avenues and dramatically expand the
      catalogue of existing biomaterials. Herein, we designed the strategy based on in
      vivo production of extracellular Pseudomonas fluorescens GK13 (PhaZGK13)
      depolymerase to degrade previously biosynthesized polyhydroxyalkanotes (PHAs) or
      to obtain 3-hydroxyalkanoic acids (HAs). With this aim, extracellular PhaZGK13
      was produced in recombinant strains and the optimal conditions for controlled
      release of HAs and oligomers by growing cells were set up with a particle
      suspension of (14)C-labelled PHA, being maximal after 24h of incubation. Genetic
      modification of key factors involved in fatty acids metabolism revealed the
      influence of an active beta-oxidation pathway on the extracellular degradation of
      PHA and subsequent HAs isolation. The highest HAs production was obtained using
      Pseudomonas putida KT2442 fadB mutant (0.27mg/mL) due to the reduced ability of
      this strain to metabolize the degradation products. The system was applied to
      produce new added value HAs harboring thioester groups in the side chain from the
      functionalized mcl-PHA, PHACOS. Remarkably, hydrolyzed PHACOS showed greater
      potential to inhibit Staphylococcus aureus(T) growth when compared to that of
      degradation products of non functionalized polyhydroxyoctanoate-co-hexanoate P(HO
      co-HH). 

PMID- 24751506
TI  - Biological activities and potential health benefits of polysaccharides from Poria
      cocos and their derivatives.
AB  - Poria cocos has a long history of medicinal use in Asian countries such as China,
      Japan, Korea and Thailand. It is a kind of edible and pharmaceutical mushroom.
      The chemical compositions of Poria cocos mainly include triterpenes,
      polysaccharides, steroids, amino acids, choline, histidine, etc. Great advances
      have been made in chemical and bioactive studies on Poria cocos polysaccharides
      (PCP) and their derivatives in recent decades. These PCP and their derivatives
      exhibit many beneficial biological activities including anticancer, anti
      inflammatory, antioxidant and antiviral activities. Therefore, PCP and their
      derivatives have great potential for further development as therapy or adjuvant
      therapy for cancer, immune-modulatory and antiviral drugs. This paper presents an
      overview of biological activities and potential health benefits of PCP and their
      derivatives. 

PMID- 24751507
TI  - A role for the regulator PsrA in the polyhydroxyalkanoate metabolism of
      Pseudomonas putida KT2440.
AB  - Pseudomonas putida KT2440 is a Gram-negative bacterium capable of producing
      medium-chain-length-polyhydroxyalkanoates (mcl-PHA). When fatty acids are used as
      growth and polymer precursors, the biosynthesis is linked to fatty acid
      metabolism via beta-oxidation route. In the close-related Pseudomonas aeruginosa,
      the transcriptional repressor PsrA regulates the beta-oxidation, but little is
      known about the regulatory system in P. putida. To analyze the effect of the
      absence of psrA gene on the growth and PHA production in P. putida, a set of
      different carbon sources were assayed in the wild type strain and in a generated
      psrA deficient strain (KT40P). The growth rates were in all cases, lower for the
      mutant. The amount of PHA produced by the mutant strain is lower than the wild
      type. Moreover, the monomeric composition seems to be different among the
      strains, as there is enrichment in monomers with shorter carbon length in the
      mutant strain. To understand the role of the psrA gene on the metabolism of fatty
      acids, we have determined the expression profile of several genes related to
      fatty acid metabolism in the wild type and in the mutant strain. The results
      indicated that PsrA mostly negatively regulate genes related to fatty acid
      metabolism. 

PMID- 24751508
TI  - Impact of glycerol and nitrogen concentration on Enterobacter A47 growth and
      exopolysaccharide production.
AB  - Enterobacter A47 produces a fucose-containing exopolysaccharide (EPS) by
      cultivation in mineral medium supplemented with glycerol. EPS synthesis by
      Enterobacter A47 was shown to be influenced by both the initial glycerol and
      nitrogen concentrations and by the nutrients' feeding rate during the fed-batch
      phase. Initial nitrogen concentrations above 1.05g/L were detrimental for EPS
      synthesis: the productivity was reduced to 0.35-0.62g/Ld (compared to 1.89
      2.04g/Ld under lower nitrogen concentrations) and the polymer had lower fucose
      content (14-17%mol, compared to 36-38%mol under lower nitrogen concentrations).
      On the other hand, EPS productivity was improved to 5.66g/Ld by increasing the
      glycerol and nitrogen feeding rates during the fed-batch phase. However, the EPS
      thus obtained had lower fucose (26%mol) and higher galactose (34%mol) contents,
      as well as lower average molecular weight (7.2*10(5)). The ability of
      Enterobacter A47 to synthesize EPS with different physico-chemical
      characteristics may be useful for the generation of biopolymers with distinct
      functional properties suitable for different applications. 

PMID- 24751509
TI  - Recovery of amorphous polyhydroxybutyrate granules from Cupriavidus necator cells
      grown on used cooking oil.
AB  - Used cooking oil (UCO) was employed as the sole carbon source for the production
      of polyhydroxybutyrate (PHB) by cultivation in batch mode of Cupriavidus necator
      DSM 428. The produced biomass was used for extraction of the PHB granules with a
      solvent-free approach using sodium dodecyl sulfate (SDS),
      ethylenediaminetetraacetic acid (EDTA), and the enzyme Alcalase in an aqueous
      medium. The recovered PHB granules showed a degree of purity higher than 90% and
      no crystallization (i.e., granules were recovered in their 'native' amorphous
      state) as demonstrated by wide angle X-ray diffraction (WAXS). Granules were
      characterized according to their thermal properties and stability by differential
      scanning calorimetry (DSC), and thermogravimetric analysis (TGA). Results show
      that UCO can be used as a renewable resource to produce amorphous PHB granules
      with excellent properties in a biocompatible manner. 

PMID- 24751510
TI  - Pectin functionalized with natural fatty acids as antimicrobial agent.
AB  - Several pectin derivatives were prepared by chemical modifications of the
      polysaccharide with natural fatty acids. The obtained biodegradable pectin-based
      materials, pectin-linoleate, pectin-oleate and pectin-palmitate, were
      investigated for their antimicrobial activity against several bacterial strains,
      Staphylococcus aureus and Escherichia coli. Good results were obtained for pectin
      oleate and pectin-linoleate, which inhibit the growth of the selected
      microorganisms by 50-70%. They exert the better antimicrobial activity against S.
      aureus. Subsequently, the pectin-oleate and the pectin-linoleate samples were
      coated on polyethylene films and were assessed for their capacity to capture the
      oxygen molecules, reducing its penetration into the polymeric support. These
      results confirmed a possible application of the new materials in the field of
      active food packaging. 

PMID- 24751511
TI  - Sizing up the poly(A) tail: insights from deep sequencing.
AB  - Global investigation of poly(A) tails has been hindered by technical challenges.
      In a recent advance, two groups developed deep sequencing methods to globally
      interrogate poly(A) tail length and sequence with high precision, opening new
      avenues for investigation of poly(A) tail functions in mRNA metabolism. Initial
      applications of these methods reveal insights into the relationship between
      poly(A) tail length and translational efficiency, and identify widespread
      uridylation and guanylation at the 3' ends of transcripts. 

PMID- 24751512
TI  - Aortic valve replacement in octogenarians.
AB  - BACKGROUND: With improved life expectancy more octogenarians now present with
      aortic valve disease. Cardiac surgery in this group of patients has previously
      been considered high risk due to co-morbidities and challenges of rehabilitation.
      This study seeks to challenge the concept of octogenarian cardiac surgery
      "unsuitability" by analysing operative outcomes and long term survival following
      aortic valve replacement. METHODS: Eighty-seven consecutive patients undergoing
      aortic valve replacement between 2000 and 2009 at St Vincent's Hospital were
      retrospectively identified. Statistical analysis was performed using SPSS
      (version 15 and 19). RESULTS: The average age was 82.7 +/- 2.4 years. The mean
      logistic EuroSCORE was 18.86 +/- 14.11. Post-operatively, four patients required
      insertion of a permanent pacemaker (4.6%) and five patients had a myocardial
      infarction (5.8%). In-hospital mortality was 3.4%. Follow-up was 93.1% complete.
      One-year survival was 92.9%, three-year survival was 86.7% and five-year survival
      was 75.0%. At follow-up 98.1% of patients were New York Heart Association (NYHA)
      Class I or II. CONCLUSIONS: Results were excellent despite reasonable co
      morbidities and Euroscore risk. Survival was impressive and the NYHA class
      reflected the success of the surgery in relieving the pathological aortic valve
      process. Patient age should not be the primary exclusion for cardiac surgery for
      aortic valve disease.

PMID- 24751513
TI  - Circumflex coronary artery to left atrium fistula caused by mitral isthmus
      ablation.
AB  - Mitral isthmus ablation is an important component of catheter ablation for
      persistent atrial fibrillation and mitral isthmus dependent flutters. We describe
      a case where mitral isthmus ablation caused a fistula between the left circumflex
      artery and the left atrium and symptomatic ischaemia. The fistula was
      successfully closed with a covered stent. 

PMID- 24751514
TI  - Nanoencapsulation in lipid-core nanocapsules controls mometasone furoate skin
      permeability rate and its penetration to the deeper skin layers.
AB  - AIMS: The influence of nanoencapsulation of mometasone furoate (MF) in
      poly(epsilon-caprolactone) lipid-core nanocapsules (LNC) on its in vitro human
      skin permeation and penetration was evaluated. METHODS: Semisolid formulations
      were prepared by increasing the viscosity of LNC using a carbomer (Carbopol((r))
      Ultrez at 0.5% w/v). Two complementary techniques (the static Franz diffusion
      cell model and the Saarbrucken penetration model) were used to evaluate skin
      permeation/penetration. RESULTS: The drug release rate was decreased by
      nanoencapsulation. The skin permeability of MF was controlled by the
      nanoencapsulation as well as by increasing the viscosity. Furthermore, the
      formulation containing the nanoencapsulated MF controlled the amount of drug
      reaching the deeper skin layers without changing its accumulation in the stratum
      corneum. CONCLUSION: This formulation is suitable for prolonged treatment of skin
      disorders which should avoid systemic absorption.

PMID- 24751515
TI  - Stromal cell-derived factor-1-3'A polymorphism is associated with decreased risk
      of myocardial infarction and early endothelial disturbance.
AB  - AIM: Genome-wide association studies have identified single-nucleotide
      polymorphisms at the 10q11 locus as risk factors for myocardial infarction (MI).
      This locus lies upstream (~80 kb) of the stromal cell-derived factor-1 (SDF1)
      gene that codify for a chemokine with protective atherogenetic effects and with a
      major role in the mobilization, homing, and differentiation of endothelial
      progenitor cells (EPCs). The purpose of this study was to investigate the
      possible association of SDF1-3'A polymorphism, that upregulates SDF1 protein
      expression, with MI and early endothelial dysfunction and atherosclerosis in
      young healthy subjects. METHODS: 200 patients (181 men age 57.3 +/- 7.7 years)
      and 230 healthy controls (96 men, age 52 +/- 11.9 years) were recruited to
      investigate the association between MI and SDF1-3'A polymorphism. The
      relationship between SDF1-3'A polymorphism and brachial artery flow-mediated
      dilation and the number of circulating EPCs was examined in 50 healthy young
      adults. RESULTS: A significant difference in SDF1-3'A genotype distribution was
      observed between patients and controls (P = 0.006). Patients carrying the A
      allele had a significantly reduced MI risk compared with subjects with GG
      genotype (odds ratio = 0.5, 95% CI = 0.3-0.9, P = 0.001). SDF1-3'A polymorphism
      presented a significant interaction with other cardiovascular risk factors
      (Pinteraction < 0. 0001). Controls carrying the A allele showed significantly
      higher flow-mediated dilation (13.9 +/- 4.9 vs 10.8 +/- 4.3, P = 0.03) and
      significantly higher values of EPCs (0.029 +/- 0.009 vs 0.022 +/- 0.008, P =
      0.02) compared with GG homozygotes. CONCLUSION: SDF1-3'A polymorphism is
      associated with a decreased risk of MI and early endothelial dysfunction,
      strongly confirming the important atherogenic role of SDF1 gene at clinical
      level.

PMID- 24751516
TI  - Patient education after acute myocardial infarction: cardiologists should adapt
      their message--French registry of acute ST-elevation or non-ST-elevation
      myocardial infarction 2010 registry.
AB  - AIMS: A shorter time delay between onset of symptoms and first call for medical
      attention would be expected in patients with a history of ischemic heart disease
      (IHD). We aimed to determine whether time to first call for an ST-elevation
      myocardial infarction (STEMI) differed between patients with or without history
      of coronary artery disease from the French registry of acute ST-elevation or non
      ST-elevation myocardial infarction (FAST-MI) 2010 registry. METHODS: FAST-MI 2010
      is a nationwide French registry that included 4169 patients with acute myocardial
      infarction (AMI, 2193 STEMI) at the end of 2010 in 213 centers. Factors
      correlated with time to first call were assessed, with a specific emphasis on
      previous history of IHD (IHD+; n = 402), compared with patients without history
      of IHD (IHD-; n = 1791). RESULTS: Time from onset to first call was 222 +/- 420
      min (median time 68 min) in IHD+ patients versus 240 +/- 4423 min (median time 75
      min) in IHD- patients (P = 0.28). In multivariate analysis, only a few factors
      were significantly related to a shorter time from onset to first call (<=75min);
      time of onset during the day (7:00 a.m. to 11:00 p.m.), upper socioeconomic
      class, anterior MI, cardiac arrest as the initial symptom, whereas history of IHD
      was not associated with a shorter time delay (odds ratio 0.86; 95% confidence
      interval 0.70-1.05). Similar results were found between patients with previous
      AMI and IHD- patients. CONCLUSION: Patients with a history of IHD do not call
      earlier than IHD-naive patients when they are confronted with symptoms of AMI.
      Cardiologists should spend more time educating their coronary patients to
      recognize symptoms of AMI.Clinicaltrials.gov identifier: NCT01237418.

PMID- 24751517
TI  - Lipoblastomatosis on the sole showing spontaneous regression.

PMID- 24751518
TI  - Resistance to cyclosporin A derives from mutations in hepatitis C virus
      nonstructural proteins.
AB  - Cyclosporine A (CsA) is an immunosuppressive drug that targets cyclophilins,
      cellular cofactors that regulate the immune system. Replication of hepatitis C
      virus (HCV) is suppressed by CsA, but the molecular basis of this suppression is
      still not fully understood. To investigate this suppression, we cultured HCV
      replicon cells (Con1, HCV genotype 1b, FLR-N cell) in the presence of CsA and
      obtained nine CsA-resistant FLR-N cell lines. We determined full-length HCV
      sequences for all nine clones, and chose two (clones #6 and #7) of the nine
      clones that have high replication activity in the presence of CsA for further
      analysis. Both clones showed two consensus mutations, one in NS3 (T1280V) and the
      other in NS5A (D2292E). Characterization of various mutants indicated that the
      D2292E mutation conferred resistance to high concentrations of CsA (up to 2 MUM).
      In addition, the missense mutation T1280V contributed to the recovery of colony
      formation activity. The effects of these mutations are also evident in two
      established HCV replicon cell lines-HCV-RMT ([1], genotype 1a) and JFH1 (genotype
      2a). Moreover, three other missense mutations in NS5A-D2303H, S2362G, and E2414K
      enhanced the resistance to CsA conferred by D2292E; these double or all quadruple
      mutants could resist approximately 8- to 25-fold higher concentrations of CsA
      than could wild-type Con1. These four mutations, either as single or
      combinations, also made Con1 strain resistant to two other cyclophilin
      inhibitors, N-methyl-4-isoleucine-cyclosporin (NIM811) or Debio-025.
      Interestingly, the changes in IC50 values that resulted from each of these
      mutations were the lowest in the Debio-025-treated cells, indicating its highest
      resistant activity against the adaptive mutation.

PMID- 24751520
TI  - Regulatory effect of the glial Golli-BG21 protein on the full-length murine small
      C-terminal domain phosphatase (SCP1, or Golli-interacting protein).
AB  - The gene in the oligodendrocyte lineage (golli) encodes a number of proteins
      essential for myelination, comprising Golli and classic isoforms that are
      expressed in a developmentally-regulated manner. The Golli-interacting-protein
      (GIP) was previously discovered in a search for potential interacting partners of
      the Golli-isoform BG21, and was realised to be an acidic phosphatase belonging to
      the family of RNA-polymerase-2, small-subunit, C-terminal phosphatases (viz.,
      SCP1). Here, we refer to this protein as mSCP1/GIP. In subsequent in vitro
      studies of recombinant murine SCP1/GIP, the inability to produce an active full
      length version of the protein under native conditions necessitated the study of a
      truncated form DeltaN-rmSCP1/GIP, but with inconclusive results regarding its
      interaction with BG21 [13]. We have since developed a new SUMO-expression and
      purification protocol for the preparation of a functional, full-length mGIP/SCP1,
      with no additional purification tags. Here, the interaction between mSCP1/GIP
      (with intact N-terminus) and BG21 is shown to be different than for the
      truncation mutant studied previously. Specifically, this interaction shows a dual
      effect on the enzymatic activity of mSCP1/GIP by BG21: BG21 enhanced mSCP1/GIP
      phosphatase activity (Ka = 30 MUM), whereas PKCalpha-phosphorylated BG21
      inhibited its activity (Ki = 2.9 MUM), suggesting a potential role of BG21 as a
      molecular switch ("quick-brake mechanism") on mSCP1/GIP. The successful
      production of an active, full-length mSCP1/GIP thus demonstrates a role for its N
      terminus in regulation of phosphatase activity, in events such as the regulation
      of transcription in oligodendrocytes.

PMID- 24751519
TI  - IKK-beta/NF-kappaB p65 mediates p27(Kip1) protein degradation in arsenite
      response.
AB  - p27(Kip1) is a potent inhibitor of the cyclin-dependent kinases that drive G1 to
      S phase transition. Since deregulation of p27(Kip1) is found in many malignancies
      and is associated with the poor prognosis, elucidation of the molecular bases for
      regulation of p27(Kip1) expression is of great significance, not only in
      providing insight into the understanding of biological p27(Kip1), but also in the
      development of new cancer therapeutic tactics. We here explored the inhibitory
      regulation of IKKbeta on p27(Kip1) expression following arsenite exposure. We
      found that although the basal level of p27(Kip1) expression in the IKKbeta(-/-)
      cells is much lower than that in the IKKbeta(+/+) cells, the deletion of IKKbeta
      in the MEFs led to a marked increase in p27(Kip1) protein induction due to
      arsenite exposure in comparison to that in the IKKbeta(+/+) cells. The IKKbeta
      regulatory effect on p27(Kip1) expression was also verified in the IKKbeta(-/-)
      and IKKbeta(-/-) cells with IKKbeta reconstitutional expression, IKKbeta(-/-)
      (IKKbeta). Further studies indicated that IKKbeta-mediated p27(Kip1)
      downregulation occurred at protein degradation level via p65-dependent and p50
      independent manner. Moreover, the results obtained from the comparison of
      arsenite-induced GSK3beta activation among transfectants of WT, IKKbeta(-/-) and
      IKKbeta(-/-) (IKKbeta), and the utilization of GSKbeta shRNA, demonstrated that
      IKKbeta regulation of p27 protein degradation was mediated by GSK3beta following
      arsenite exposure. 

PMID- 24751521
TI  - Molecular cloning, characterization and expression of a gene encoding
      phosphoketolase from Termitomyces clypeatus.
AB  - A phosphoketolase (pk) gene from the fungus Termitomyces clypeatus (TC) was
      cloned and partially characterized. Oligonucleotide primers specific for the
      phosphoketolase gene (pk) were designed from the regions of homologies found in
      the primary structure of the enzyme from other fungal sources related to TC,
      using multiple sequence alignment technique. The cDNA of partial lengths were
      amplified, cloned and sequenced in three parts by 3' and 5' RACE and RT-PCR using
      these oligonucleotide primers. The full length ds cDNA was constructed next by
      joining these three partial cDNA sequences having appropriate overlapping regions
      using Overlap Extension PCR technique. The constructed full length cDNA exhibited
      an open reading frame of 2487 bases and 5' and 3' UTRs. The deduced amino acid
      sequence, which is of 828 amino acids, when analyzed with NCBI BLAST, showed high
      similarities with the phosphoketolase enzyme (Pk) superfamily with expected
      domains. The part of the TC genomic DNA comprising of the pk gene was also
      amplified, cloned and sequenced and was found to contain two introns of 68 and 74
      bases that interrupt the pk reading frame. The coding region of pk cDNA was
      subcloned in pKM260 expression vector in correct frame and the protein was
      expressed in Escherichia coli BL21 (DE3) transformed with this recombinant
      expression plasmid. The recombinant protein purified by His-tag affinity
      chromatography indicated the presence of a protein of the expected size. In vivo
      expression studies of the gene in presence of different carbon sources indicated
      synthesis of Pk specific mRNA, as expected. Phylogenetic studies revealed a
      common ancestry of the fungal and bacterial Pk. The TC is known to secrete
      several industrially important enzymes involved in carbohydrate metabolism.
      However, the presence of Pk, a key enzyme in pentose metabolism, has not been
      demonstrated conclusively in this organism. Cloning, sequencing and expression
      study of this gene establishes the functioning of this gene in T. clypeatus. The
      Pk from TC is a new source for commercial exploitation. 

PMID- 24751522
TI  - miR-613 regulates cholesterol efflux by targeting LXRalpha and ABCA1 in PPARgamma
      activated THP-1 macrophages.
AB  - Cholesterol efflux from macrophages is a critical mechanism to prevent the
      development of atherosclerosis. Although PPARgamma is known to be a potent sterol
      sensor that play a fundamental role in cholesterol metabolism, the potential
      effects of PPARgamma responsive miRNA still need to be revealed. In this study,
      we found that miR-613 is inversely correlated with LXRalpha and ABCA1 in
      PPARgamma activated THP-1 cells. PPARgamma negatively regulates the expression of
      miR-613 at transcriptional level, and miR-613 suppressed LXRalpha and ABCA1 by
      targeting the 3'-UTR of their mRNAs. Furthermore, downregulation of LXRalpha and
      ABCA1 by miR-613 inhibited cholesterol efflux from PPARgamma activated THP-1
      macrophages. These results revealed an alternative mechanism for PPARgamma
      regulation and provided a potential target for the treatment of cholesterol
      metabolic diseases. 

PMID- 24751523
TI  - Combinatorial reshaping of a lipase structure for thermostability: additive role
      of surface stabilizing single point mutations.
AB  - Thermostable lipases are of high priority for industrial applications. In the
      present study, targeted improvement of the thermostability of a lipase from
      metagenomic origin was examined by using a combinatorial protein engineering
      approach exploring additive effects of single amino acid substitutions. A variant
      (LipR5) was generated after combination of two thermostabilizing mutations (R214C
      & N355K). Thermostability of the variant enzyme was analyzed by half-life
      measurement and circular dichroism (CD). To assess whether catalytic properties
      were affected by mutation, the optimal reaction conditions were determined. The
      protein LipR5, displayed optimum activity at 50 degrees C and pH 8.0. It showed
      two fold enhancement in thermostability (at 60 degrees C) as compared to LipR3
      (R214C) and nearly 168 fold enhancement as compared to parent enzyme (LipR1).
      Circular dichroism and fluorescence study suggest that the protein structure had
      become more rigid and stable to denaturation. Study of 3D model suggested that
      Lys355 was involved in formation of a Hydrogen bond with OE1 of Glu284. Lys355
      was also making salt bridge with OE2 of Glu284. 

PMID- 24751524
TI  - Widespread eosinophilic pustular folliculitis in a nonimmunocompromised patient.
AB  - OBJECTIVE: We present a case of eosinophilic pustular folliculitis, a rare
      dermatosis which is often associated with HIV infection or internal malignancies.
      CLINICAL PRESENTATION AND INTERVENTION: We report the case of a 66-year-old man
      with a medical history of hypertension. Histopathological examination showed a
      dense follicular inflammatory infiltrate with abundant eosinophils. The clinical
      response to indomethacin was excellent with no recurrence during the follow-up.
      CONCLUSION: The patient responded well to indomethacin treatment.

PMID- 24751525
TI  - Frataxin deficiency in neonatal rat ventricular myocytes targets mitochondria and
      lipid metabolism.
AB  - Friedreich ataxia (FRDA) is a hereditary disease caused by deficient frataxin
      expression. This mitochondrial protein has been related to iron homeostasis,
      energy metabolism, and oxidative stress. Patients with FRDA experience neurologic
      alterations and cardiomyopathy, which is the leading cause of death. The specific
      effects of frataxin depletion on cardiomyocytes are poorly understood because no
      appropriate cardiac cellular model is available to researchers. To address this
      research need, we present a model based on primary cultures of neonatal rat
      ventricular myocytes (NRVMs) and short-hairpin RNA interference. Using this
      approach, frataxin was reduced down to 5 to 30% of control protein levels after 7
      days of transduction. At this stage the activity and amount of the iron-sulfur
      protein aconitase, in vitro activities of several OXPHOS components, levels of
      iron-regulated mRNAs, and the ATP/ADP ratio were comparable to controls. However,
      NRVMs exhibited markers of oxidative stress and a disorganized mitochondrial
      network with enlarged mitochondria. Lipids, the main energy source of heart
      cells, also underwent a clear metabolic change, indicated by the increased
      presence of lipid droplets and induction of medium-chain acyl-CoA dehydrogenase.
      These results indicate that mitochondria and lipid metabolism are primary targets
      of frataxin deficiency in NRVMs. Therefore, they contribute to the understanding
      of cardiac-specific mechanisms occurring in FRDA and give clues for the design of
      cardiac-specific treatment strategies for FRDA. 

PMID- 24751527
TI  - On-chip in vitro cell-network pre-clinical cardiac toxicity using spatiotemporal
      human cardiomyocyte measurement on a chip.
AB  - To overcome the limitations and misjudgments of conventional prediction of
      arrhythmic cardiotoxicity, we have developed an on-chip in vitro predictive
      cardiotoxicity assay using cardiomyocytes derived from human stem cells employing
      a constructive spatiotemporal two step measurement of fluctuation (short-term
      variability; STV) of cell's repolarization and cell-to-cell conduction time,
      representing two origins of lethal arrhythmia. Temporal STV of field potential
      duration (FPD) showed a potential to predict the risks of lethal arrhythmia
      originated from repolarization dispersion for false negative compounds, which was
      not correctly predicted by conventional measurements using animal cells, even for
      non-QT prolonging clinical positive compounds. Spatial STV of conduction time
      delay also unveiled the proarrhythmic risk of asynchronous propagation in cell
      networks, whose risk cannot be correctly predicted by single-cell-based
      measurements, indicating the importance of the spatiotemporal fluctuation
      viewpoint of in vitro cell networks for precise prediction of lethal arrhythmia
      reaching clinical assessment such as thorough QT assay. 

PMID- 24751528
TI  - Clinical imaging assessments of knee osteoarthritis in the elderly: a mini
      review.
AB  - Knee osteoarthritis (OA) in the elderly is one of the most common degenerative
      age-related joint diseases leading to typical degradation of articular cartilage
      with severe pain and limitation of joint motion. Its increasing prevalence due to
      the demographic development of the society has major implications for individual
      and public healthcare with the increasing necessity for clinical imaging
      assessment in a high number of individuals. Although conventional X-ray
      radiographs are widely considered as gold standard for the assessment of knee OA,
      in clinical and scientific settings they increasingly bare significant
      limitations in situations when high resolution and detailed assessment of
      cartilage is demanded. New imaging modalities are broadening the possibilities in
      knee OA clinical practice and are offering new insights to help for a better
      understanding of the disease. X-ray analysis in OA of the knee is associated with
      many technical limitations and increasingly is replaced by high-quality
      assessment using magnetic resonance imaging or ultrasonography both in clinical
      routine and scientific situations. These novel imaging modalities enable an in
      vivo visualization of the quality of the cartilaginous structure and bone as well
      as all articular and periarticular tissues. Therefore, the limitations of
      radiographs in knee OA assessment could be overcome by these techniques. This
      review article should provide an insight into the most important radiological
      features of knee OA and their systematic visualization with different imaging
      approaches that can be used in clinical routine.

PMID- 24751526
TI  - Circulating membrane-derived microvesicles in redox biology.
AB  - Microparticles or microvesicles (MVs) are subcellular membrane blebs shed from
      all cells in response to various stimuli. MVs carry a battery of signaling
      molecules, many of them related to redox-regulated processes. The role of MVs,
      either as a cause or as a result of cellular redox signaling, has been
      increasingly recognized over the past decade. This is in part due to advances in
      flow cytometry and its detection of MVs. Notably, recent studies have shown that
      circulating MVs from platelets and endothelial cells drive reactive species
      dependent angiogenesis; circulating MVs in cancer alter the microenvironment and
      enhance invasion through horizontal transfer of mutated proteins and nucleic
      acids and harbor redox-regulated matrix metalloproteinases and procoagulative
      surface molecules; and circulating MVs from red blood cells and other cells
      modulate cell-cell interactions through scavenging or production of nitric oxide
      and other free radicals. Although our recognition of MVs in redox-related
      processes is growing, especially in the vascular biology field, much remains
      unknown regarding the various biologic and pathologic functions of MVs. Like
      reactive oxygen and nitrogen species, MVs were originally believed to have a
      solely pathological role in biology. And like our understanding of reactive
      species, it is now clear that MVs also play an important role in normal growth,
      development, and homeostasis. We are just beginning to understand how MVs are
      involved in various biological processes-developmental, homeostatic, and
      pathological-and the role of MVs in redox signaling is a rich and exciting area
      of investigation. 

PMID- 24751529
TI  - Assessment of rotator cuff repair integrity using ultrasound and magnetic
      resonance imaging in a multicenter study.
AB  - BACKGROUND: This study compared ultrasound and magnetic resonance imaging (MRI)
      evaluation of the repaired rotator cuff to determine concordance between these
      imaging studies. METHODS: We performed a concordance study using the data from a
      prospective nonrandomized multicenter study at 13 centers. A suture bridge
      technique was used to repair 113 rotator cuff tears that were between 1 and 4 cm
      wide. Repairs were evaluated with MRI and ultrasound at multiple time points
      after surgery. The MRI scans were read by a central radiologist and the surgeon,
      and the ultrasounds were read by a local radiologist or the surgeon who performed
      the ultrasound. RESULTS: The concordance between the central radiologist's MRI
      reading and the investigator's MRI readings at all time points was 89%, with a
      kappa coefficient of 0.60. The concordance between the central radiologist's MRI
      and ultrasound readings at all time points was 85%, with a kappa coefficient of
      0.40. The concordance between the investigator's MRI and ultrasound readings was
      92%, with a kappa coefficient of 0.70. CONCLUSIONS: In the community setting,
      ultrasound may be used to evaluate the integrity of a repaired rotator cuff
      tendon and constitutes a comparable alternative to MRI when evaluating the
      integrity of a rotator cuff repair. Clinical investigators should compare their
      postoperative ultrasound results with their postoperative MRI results for a
      certain time period to establish the accuracy of ultrasound before relying solely
      on ultrasound imaging to evaluate the integrity of their rotator cuff repairs.

PMID- 24751530
TI  - Venous thromboembolism incidence in upper limb orthopedic surgery: do these
      procedures increase venous thromboembolism risk?
AB  - BACKGROUND: In 2005, the House of Commons (HoC) Health Committee stated deaths
      attributed to preventable, hospital-acquired venous thromboembolism (VTE)
      numbered upwards of 25,000 per annum. Nationwide prevention of VTE became the
      topic of a major health campaign. The HoC Health Committee stated there was an
      unstratified VTE risk of between 45% and 51% associated with orthopedic surgery.
      VTE research in orthopedic surgery has been concentrated on lower limb
      procedures. Experience suggests that this kind of relation does not hold true for
      upper limb orthopedic procedures. This project aimed to estimate the incidence of
      postoperative VTE in upper limb orthopedic surgery. METHODS: The incidence of
      postoperative VTE was assessed in 3357 consecutive upper limb orthopedic
      operations performed by 4 surgeons in Lancashire Teaching Hospitals National
      Health Service (NHS) Trust (LTHTR) between July 1, 2009, and July 31, 2012.
      RESULTS: Four pulmonary embolisms and 2 deep vein thromboses occurred. Incidence
      of postoperative VTE was 0.0018%, significantly lower than rates reported in the
      literature. Five of 6 patients who developed a VTE reported a personal or family
      history of VTE. Three patients would not have been identified as at risk under
      the current VTE screening guidelines. Three of these patients received
      appropriate anticoagulation according to present guidelines, yet VTE events still
      occurred. CONCLUSION: These results indicate VTE risk in orthopedic upper limb
      surgery is much lower than reported in the literature. The necessity for
      screening for VTE in upper limb surgery is contested. The efficacy of VTE
      screening and current VTE prophylaxis is discussed, and an alternative and much
      simplified method of screening is suggested.

PMID- 24751531
TI  - Perioperative complications after hemiarthroplasty and total shoulder
      arthroplasty are equivalent.
AB  - BACKGROUND: Total shoulder arthroplasty (TSA) results in superior clinical
      outcomes to hemiarthroplasty (HA); however, TSA is a more technical and invasive
      procedure. This study retrospectively compares perioperative complications after
      HA and TSA using the National Surgical Quality Improvement Program (NSQIP)
      database. METHODS: The NSQIP user file was queried for HA and TSA cases from the
      years 2005 through 2010. Major complications were defined as life-threatening or
      debilitating. All complications occurred within 30 days of the initial procedure.
      We performed multivariate analysis to compare complication rates between the two
      procedures, controlling for patient comorbidities. RESULTS: The database returned
      1,718 patients (HA in 30.4% [n = 523] and TSA in 69.6% [n = 1,195]). The major
      complication rates in the HA group (5.2%, n = 29) and TSA group (5.1%, n = 61)
      were similar (P = .706). Rates of blood transfusions for postoperative bleeding
      in patients undergoing HA (2.3%, n = 12) and TSA (2.9%, n = 35) were
      indistinguishable (P = .458). Venous thromboembolism was a rare complication,
      occurring in 0.4% of patients in each group (2 HA patients and 5 TSA patients, P
      > .999). On multivariate analysis, the operative procedure was not associated
      with major complications (P = .349); however, emergency case, pulmonary
      comorbidity, anemia with a hematocrit level lower than 36%, and wound class of
      III or IV increased the risk of a major complication (P < .05 for all).
      CONCLUSION: Multivariate analysis of patients undergoing TSA or HA in the NSQIP
      database suggests that patient factors-not the procedure being performed-are
      significant predictors of major complications. Controlling for patient
      comorbidities, we found no increased risk of perioperative major complications in
      patients undergoing TSA compared with HA.

PMID- 24751532
TI  - Load transfer after cemented total shoulder arthroplasty.
AB  - BACKGROUND: Glenoid loosening is the primary reason for failure after a total
      shoulder arthroplasty (TSA), but the failure mechanism is not yet known. This
      study determined how the load transfer and stress distribution are affected by
      the introduction of a glenoid implant. METHODS: We developed a finite-element
      model of a scapula with and without a virtually implanted modern glenoid
      prosthesis design. Two load magnitudes were considered: normal and high. Loading
      locations were simulated at the center and at 4 eccentric positions on the
      glenoid. A metal-backed implant was also simulated to understand the effect of
      fixation stiffness. RESULTS: In the intact glenoid, for both center and eccentric
      loading, the majority of stress was distributed in the cancellous bone, whereas
      after a reconstruction, stresses in that region were lower. Metal-backed implants
      further decreased the joint load carried by the bone. Stresses in the cement
      layer increased during eccentric and high-magnitude loading. CONCLUSION: This
      study provided a basic understanding of the load-sharing phenomenon after a TSA
      that could explain glenoid loosening failure. Our results suggest that with
      reconstruction of the glenoid with a contemporary implant, the load transfer
      pattern is significantly altered, with eccentric and high-magnitude loads
      increasing stresses in the cement indicating potential for failure. The use of a
      metal-backed implant reduces the load carried by the bone, which may be
      detrimental to long-term TSA survival.

PMID- 24751533
TI  - Dynamic analysis of the ulnar nerve in the cubital tunnel using ultrasonography.
AB  - BACKGROUND: We investigated the dynamics of the ulnar nerve during elbow flexion
      and the relationships between these dynamics and the morphology of the ulnar
      nerve groove in healthy individuals. MATERIALS AND METHODS: Twenty healthy
      volunteers (40 elbows) underwent ultrasonographic examination of the ulnar nerve
      at the elbow. We measured the breadth and depth of the ulnar nerve groove at 90
      degrees  of elbow flexion and calculated the depth-to-breadth ratio. We recorded
      the distance from the trochlea of the humerus to the nerve and the short-axis
      diameter of the nerve at 30 degrees , 60 degrees , 90 degrees , and 120 degrees 
      of elbow flexion. We calculated the medial shift and flattening of the ulnar
      nerve at each angle relative to 30 degrees  of flexion, compared the values among
      the different angles, and compared the depth-to-breadth ratio with the location,
      medial shift, and flattening ratio of the ulnar nerve. RESULTS: The medial shift
      was significantly greater at 120 degrees  than at other angles (P < .001).
      Flattening increased with increasing elbow flexion and was significantly
      different at 60 degrees , 90 degrees , and 120 degrees  (all P < .001). The
      flattening ratios were significantly correlated with the depth-to-breadth ratio
      at 120 degrees  (r = -0.43, P = .005). CONCLUSIONS: The ulnar nerve moves
      medially and is flattened with the elbow flexed between 90 degrees  and 120
      degrees . When the ulnar nerve groove is shallow, high degrees of elbow flexion
      result in flattening of the ulnar nerve in the groove.

PMID- 24751534
TI  - Degradable hydrogels for spatiotemporal control of mesenchymal stem cells
      localized at decellularized bone allografts.
AB  - The transplantation of cells, such as mesenchymal stem cells (MSCs), has numerous
      applications in the field of regenerative medicine. For cell transplantation
      strategies to be successful therapeutically, cellular localization and
      persistence must be controlled to maximize cell-mediated contributions to
      healing. Herein, we demonstrate that hydrolytic degradation of poly(ethylene
      glycol) (PEG) hydrogels can be used to spatiotemporally control encapsulated MSC
      localization to decellularized bone allografts, both in vitro and in vivo. By
      altering the number of hydrolytically degradable lactide repeat units within PEG
      d,l-lactide-methacrylate macromers, a series of hydrogels was synthesized that
      degraded over ~1, 2 and 3weeks. MSCs were encapsulated within these hydrogels
      formed around decellularized bone allografts, and non-invasive, longitudinal
      fluorescence imaging was used to track cell persistence both in vitro and in
      vivo. Spatiotemporal localization of MSCs to the exterior of bone allograft
      surfaces was similar to in vitro hydrogel degradation kinetics despite hydrogel
      mesh sizes being ~2-3 orders of magnitude smaller than MSC size throughout the
      degradation process. Thus, localized, cell-mediated degradation and MSC migration
      from the hydrogels are suspected, particularly as ~10% of the total transplanted
      MSC population was shown to persist in close proximity (within ~650MUm) to grafts
      7weeks after complete hydrogel degradation. This work demonstrates the
      therapeutic utility of PEG-based hydrogels for controlling spatiotemporal cell
      transplantation for a myriad of regenerative medicine strategies. 

PMID- 24751535
TI  - Breaching the nuclear envelope in development and disease.
AB  - In eukaryotic cells the nuclear genome is enclosed by the nuclear envelope (NE).
      In metazoans, the NE breaks down in mitosis and it has been assumed that the
      physical barrier separating nucleoplasm and cytoplasm remains intact during the
      rest of the cell cycle and cell differentiation. However, recent studies suggest
      that nonmitotic NE remodeling plays a critical role in development, virus
      infection, laminopathies, and cancer. Although the mechanisms underlying these NE
      restructuring events are currently being defined, one common theme is activation
      of protein kinase C family members in the interphase nucleus to disrupt the
      nuclear lamina, demonstrating the importance of the lamina in maintaining nuclear
      integrity. 

PMID- 24751536
TI  - PINK1 phosphorylates ubiquitin to activate Parkin E3 ubiquitin ligase activity.
AB  - PINK1 kinase activates the E3 ubiquitin ligase Parkin to induce selective
      autophagy of damaged mitochondria. However, it has been unclear how PINK1
      activates and recruits Parkin to mitochondria. Although PINK1 phosphorylates
      Parkin, other PINK1 substrates appear to activate Parkin, as the mutation of all
      serine and threonine residues conserved between Drosophila and human, including
      Parkin S65, did not wholly impair Parkin translocation to mitochondria. Using
      mass spectrometry, we discovered that endogenous PINK1 phosphorylated ubiquitin
      at serine 65, homologous to the site phosphorylated by PINK1 in Parkin's
      ubiquitin-like domain. Recombinant TcPINK1 directly phosphorylated ubiquitin and
      phospho-ubiquitin activated Parkin E3 ubiquitin ligase activity in cell-free
      assays. In cells, the phosphomimetic ubiquitin mutant S65D bound and activated
      Parkin. Furthermore, expression of ubiquitin S65A, a mutant that cannot be
      phosphorylated by PINK1, inhibited Parkin translocation to damaged mitochondria.
      These results explain a feed-forward mechanism of PINK1-mediated initiation of
      Parkin E3 ligase activity. 

PMID- 24751537
TI  - BARP suppresses voltage-gated calcium channel activity and Ca2+-evoked
      exocytosis.
AB  - Voltage-gated calcium channels (VGCCs) are key regulators of cell signaling and
      Ca(2+)-dependent release of neurotransmitters and hormones. Understanding the
      mechanisms that inactivate VGCCs to prevent intracellular Ca(2+) overload and
      govern their specific subcellular localization is of critical importance. We
      report the identification and functional characterization of VGCC beta-anchoring
      and -regulatory protein (BARP), a previously uncharacterized integral membrane
      glycoprotein expressed in neuroendocrine cells and neurons. BARP interacts via
      two cytosolic domains (I and II) with all Cavbeta subunit isoforms, affecting
      their subcellular localization and suppressing VGCC activity. Domain I interacts
      at the alpha1 interaction domain-binding pocket in Cavbeta and interferes with
      the association between Cavbeta and Cavalpha1. In the absence of domain I
      binding, BARP can form a ternary complex with Cavalpha1 and Cavbeta via domain
      II. BARP does not affect cell surface expression of Cavalpha1 but inhibits Ca(2+)
      channel activity at the plasma membrane, resulting in the inhibition of Ca(2+)
      evoked exocytosis. Thus, BARP can modulate the localization of Cavbeta and its
      association with the Cavalpha1 subunit to negatively regulate VGCC activity.

PMID- 24751538
TI  - ProSAP1 and membrane nanodomain-associated syndapin I promote postsynapse
      formation and function.
AB  - Insights into mechanisms coordinating membrane remodeling, local actin
      nucleation, and postsynaptic scaffolding during postsynapse formation are
      important for understanding vertebrate brain function. Gene knockout and RNAi in
      individual neurons reveal that the F-BAR protein syndapin I is a crucial
      postsynaptic coordinator in formation of excitatory synapses. Syndapin I
      deficiency caused significant reductions of synapse and dendritic spine
      densities. These syndapin I functions reflected direct, SH3 domain-mediated
      associations and functional interactions with ProSAP1/Shank2. They furthermore
      required F-BAR domain-mediated membrane binding. Ultra-high-resolution imaging of
      specifically membrane-associated, endogenous syndapin I at membranes of freeze
      fractured neurons revealed that membrane-bound syndapin I preferentially occurred
      in spines and formed clusters at distinct postsynaptic membrane subareas.
      Postsynaptic syndapin I deficiency led to reduced frequencies of miniature
      excitatory postsynaptic currents, i.e., to defects in synaptic transmission
      phenocopying ProSAP1/Shank2 knockout, and impairments in proper synaptic
      ProSAP1/Shank2 distribution. Syndapin I-enriched membrane nanodomains thus seem
      to be important spatial cues and organizing platforms, shaping dendritic membrane
      areas into synaptic compartments. 

PMID- 24751539
TI  - Vinculin phosphorylation differentially regulates mechanotransduction at cell
      cell and cell-matrix adhesions.
AB  - Cells experience mechanical forces throughout their lifetimes. Vinculin is
      critical for transmitting these forces, yet how it achieves its distinct
      functions at cell-cell and cell-matrix adhesions remains unanswered. Here, we
      show vinculin is phosphorylated at Y822 in cell-cell, but not cell-matrix,
      adhesions. Phosphorylation at Y822 was elevated when forces were applied to E
      cadherin and was required for vinculin to integrate into the cadherin complex.
      The mutation Y822F ablated these activities and prevented cells from stiffening
      in response to forces on E-cadherin. In contrast, Y822 phosphorylation was not
      required for vinculin functions in cell-matrix adhesions, including integrin
      induced cell stiffening. Finally, forces applied to E-cadherin activated Abelson
      (Abl) tyrosine kinase to phosphorylate vinculin; Abl inhibition mimicked the loss
      of vinculin phosphorylation. These data reveal an unexpected regulatory mechanism
      in which vinculin Y822 phosphorylation determines whether cadherins transmit
      force and provides a paradigm for how a shared component of adhesions can produce
      biologically distinct functions. 

PMID- 24751541
TI  - Crystal structure of listeriolysin O reveals molecular details of oligomerization
      and pore formation.
AB  - Listeriolysin O (LLO) is an essential virulence factor of Listeria monocytogenes
      that causes listeriosis. Listeria monocytogenes owes its ability to live within
      cells to the pH- and temperature-dependent pore-forming activity of LLO, which is
      unique among cholesterol-dependent cytolysins. LLO enables the bacteria to cross
      the phagosomal membrane and is also involved in activation of cellular processes,
      including the modulation of gene expression or intracellular Ca(2+) oscillations.
      Neither the pore-forming mechanism nor the mechanisms triggering the signalling
      processes in the host cell are known in detail. Here, we report the crystal
      structure of LLO, in which we identified regions important for oligomerization
      and pore formation. Mutants were characterized by determining their haemolytic
      and Ca(2+) uptake activity. We analysed the pore formation of LLO and its
      variants on erythrocyte ghosts by electron microscopy and show that pore
      formation requires precise interface interactions during toxin oligomerization on
      the membrane. 

PMID- 24751540
TI  - Mitochondrial fusion is frequent in skeletal muscle and supports excitation
      contraction coupling.
AB  - Genetic targeting experiments indicate a fundamental role for mitochondrial
      fusion proteins in mammalian physiology. However, owing to the multiple functions
      of fusion proteins, their related phenotypes are not necessarily caused by
      altered mitochondrial fusion. Perhaps the biggest mystery is presented by
      skeletal muscle, where mostly globular-shaped mitochondria are densely packed
      into the narrow intermyofilamental space, limiting the interorganellar
      interactions. We show here that mitochondria form local networks and regularly
      undergo fusion events to share matrix content in skeletal muscle fibers. However,
      fusion events are less frequent and more stable in the fibers than in
      nondifferentiated myoblasts. Complementation among muscle mitochondria was
      suppressed by both in vivo genetic perturbations and chronic alcohol consumption
      that cause myopathy. An Mfn1-dependent pathway is revealed whereby fusion
      inhibition weakens the metabolic reserve of mitochondria to cause dysregulation
      of calcium oscillations during prolonged stimulation. Thus, fusion dynamically
      connects skeletal muscle mitochondria and its prolonged loss jeopardizes
      bioenergetics and excitation-contraction coupling, providing a potential
      pathomechanism contributing to myopathies. 

PMID- 24751542
TI  - Attachment and adjustment in adolescents and young adults with a history of
      pediatric functional abdominal pain.
AB  - OBJECTIVES: This study tested predictions of the Attachment-Diathesis Model (ADM)
      of Chronic Pain in a cross-sectional sample of adolescents and young adults with
      a history of childhood functional abdominal pain (FAP). ADM posits that
      attachment anxiety is a diathesis for poor adjustment (physical health, mental
      health, and functioning) in the context of chronic pain and that pain self
      efficacy, pain threat appraisal, and passive coping mediate this effect. METHODS:
      Participants (N=261) were recruited from a database of consecutive new patients
      evaluated for abdominal pain at a pediatric gastroenterology clinic.
      Participants' mean age at the follow-up assessment was 21 years. Structural
      equation modeling was used to test the fit of our conceptual model to the data.
      RESULTS: Model fit was good (comparative fit index=0.971, the Tucker-Lewis
      index=0.940, root mean square error of approximation=0.067). Attachment anxiety
      significantly predicted poorer health in both the mental and physical domains.
      Model fit was consistent with our hypothesis that pain self-efficacy mediates the
      effect of attachment anxiety on passive coping and that passive coping, in turn,
      mediates the effect of pain self-efficacy and pain threat appraisal on mental and
      physical health. DISCUSSION: Among individuals with a childhood history of FAP,
      those with anxious attachment may be at higher risk for poor physical and mental
      health. Pain beliefs and coping may mediate the relation between anxious
      attachment and health outcomes and may serve as effective targets for
      intervention in chronic pain.

PMID- 24751544
TI  - Drug testing challenged.

PMID- 24751545
TI  - Pain self-efficacy mediates the relationship between depressive symptoms and pain
      severity.
AB  - OBJECTIVES: We examined the relationships between depressive symptoms, pain
      severity, and pain self-efficacy (PSE) in patients with chronic low back pain
      (CLBP). We hypothesized that change in depressive symptoms would significantly
      influence change in pain severity, and that PSE indirectly affects this
      relationship. MATERIALS AND METHODS: Participants were 109 CLBP patients in a 4
      week multidisciplinary rehabilitation program for CLBP. They completed measures
      of PSE, depression, and pain severity at admission and discharge. Structural
      equation modeling was used to test the significant direct and indirect effects
      from pretreatment to posttreatment. RESULTS: Change in depressive symptoms
      significantly predicted change in pain severity in affective (beta=0.358; 95%
      confidence interval [CI], 0.206-0.480; P=0.006), sensory (beta=0.384; 95% CI,
      0.257-0.523; P=0.002), and evaluative pain (beta=0.456; 95% CI, 0.285-0.605;
      P=0.002). The indirect effects of change in PSE partially accounted for the
      relationship between change in depressive symptoms and change in sensory
      (beta=0.105; 95% CI, 0.016-0.241; P=0.023) and evaluative pain (beta=0.121; 95%
      CI, 0.010-0.249; P=0.040). The relationship between change in depressive symptoms
      and change in affective pain was fully accounted for by the indirect effect of
      change in PSE (beta=0.203; 95% CI, 0.082-0.337; P=0.002). DISCUSSION: These
      findings suggest that pain management and rehabilitation programs for CLBP should
      specifically target PSE as a key aspect of treatment.

PMID- 24751543
TI  - The role of positive affect in pain and its treatment.
AB  - OBJECTIVE: This narrative review summarizes and integrates the available
      literature on positive affect (PA) and pain to: (1) provide a brief overview of
      PA and summarize the key findings that have emerged in the study of PA and pain;
      (2) provide a theoretical foundation from which to understand how PA operates in
      the context of chronic pain (CP); and (3) highlight how the prevailing
      psychosocial treatments for CP address PA in the therapeutic context, and offer
      suggestions for how future treatment development research can maximize the
      benefit of PA for patients with CP. RESULTS: In experimental studies, the
      evidence suggests PA is analgesic. In clinical studies, the association of PA and
      pain is dynamic, time variant, and may be best considered in context of its
      interacting role with negative affect. DISCUSSION: We offer an "upward spiral"
      model of PA, resilience and pain self-management, which makes specific
      predictions that PA will buffer maladaptive cognitive and affective responses to
      pain, and promote active engagement in valued goals that enhance CP self
      management.

PMID- 24751546
TI  - Barriers to change in depressive symptoms after multidisciplinary rehabilitation
      for whiplash: the role of perceived injustice.
AB  - OBJECTIVE: Depressive symptoms complicate patients' recovery after
      musculoskeletal injury. There is strong evidence to support the utility of
      multidisciplinary approaches for treating comorbid pain and depressive symptoms.
      Despite this, a significant proportion of patients may not experience meaningful
      reductions in depressive symptoms following intervention. The purpose of this
      study was to identify barriers to change in depressive symptom during
      multidisciplinary rehabilitation for patients with whiplash injuries. METHODS: A
      total of 53 patients with clinically meaningful levels of depressive symptoms
      before participating in a standardized multidisciplinary rehabilitation program
      participated in this study. Patients completed self-report measures of depressive
      symptoms, demographic factors, pain intensity, disability, posttraumatic stress
      symptoms, pain catastrophizing, perceived injustice, and self-efficacy upon
      commencement and completion of the rehabilitation program. Analyses examined
      whether pretreatment variables predicted change in depressive symptoms over
      treatment and the maintenance of clinically meaningful levels of depressive
      symptoms at posttreatment. RESULTS: Duration of work absence and perceived
      injustice were significant unique predictors of percent change in depressive
      symptoms in a linear regression analysis. Perceived injustice was the only
      significant unique predictor of the presence of clinically meaningful levels of
      depressive symptoms at posttreatment in a logistic regression analysis.
      CONCLUSIONS: The results suggest that the identification of patients with high
      levels of perceived injustice and implementation of targeted interventions for
      these patients might contribute to greater improvements in their depressive
      symptomatology.

PMID- 24751547
TI  - Demonstration of FBRM as process analytical technology tool for dewatering
      processes via CST correlation.
AB  - The current challenges associated with the design and operation of net-energy
      positive wastewater treatment plants demand sophisticated approaches for the
      monitoring of polymer-induced flocculation. In anaerobic digestion (AD)
      processes, the dewaterability of the sludge is typically assessed from off-line
      lab-bench tests - the capillary suction time (CST) test is one of the most
      common. Focused beam reflectance measurement (FBRM) is a promising technique for
      real-time monitoring of critical performance attributes in large scale processes
      and is ideally suited for dewatering applications. The flocculation performance
      of twenty-four cationic polymers, that spanned a range of polymer size and charge
      properties, was measured using both the FBRM and CST tests. Analysis of the data
      revealed a decreasing monotonic trend; the samples that had the highest percent
      removal of particles less than 50 microns in size as determined by FBRM had the
      lowest CST values. A subset of the best performing polymers was used to evaluate
      the effects of dosage amount and digestate sources on dewatering performance. The
      results from this work show that FBRM is a powerful tool that can be used for
      optimization and on-line monitoring of dewatering processes. 

PMID- 24751548
TI  - Characterization of biofouling in a lab-scale forward osmosis membrane bioreactor
      (FOMBR).
AB  - Forward osmosis membrane bioreactors (FOMBR) provide high quality permeate,
      however the propensity for membrane biofouling in FOMBRs is unknown. Here, FOMBRs
      were operated under high and low aeration and the membrane-associated biofilms
      were characterized by confocal laser scanning microscopy (CLSM) and rRNA gene
      tagged pyrosequencing. CLSM images revealed that there was little biofilm formed
      under high aeration, while thick biofilms were observed on the membranes operated
      under low aeration. The diversity and richness of bacterial and archaeal
      communities as assessed by pyrosequencing varied under high and low aeration. The
      composition of the bacterial suspended sludge communities and the sessile biomass
      on the membrane surface, as assessed by non-metric multidimensional scaling, was
      significantly different under high aeration, but was more similar under low
      aeration. SIMPER analysis indicated that Pseudomonas, Aeromonas and Fluviicola
      preferentially attached to the membrane. The results presented here provide a
      comprehensive understanding of membrane biofouling in FOMBRs, which is essential
      for the development of effective control strategies. 

PMID- 24751549
TI  - Preface to the special issue: zebrafish immunity and infection models.

PMID- 24751550
TI  - Nutrition Support Team-Led Glycemic Control Program for Critically Ill Patients.
AB  - Glycemic control is an important component of the metabolic management of the
      critically ill patient. Nutrition support teams are frequently challenged by
      complicated patients who exhibit multiple concurrent etiologies for
      hyperglycemia. Nutrition support teams can serve in a pivotal role in the
      development and evaluation of safe and effective techniques for achieving
      glycemic control. This review describes the efforts of a nutrition support team
      in achieving safe and effective glycemic control at their institution.
      Identification of target blood glucose concentration range, development,
      initiation, monitoring of a continuous intravenous insulin infusion algorithm,
      nursing adherence to the algorithm, modification of the algorithm based on the
      presence of conditions that alter insulin metabolism and glucose homeostasis, and
      transition of the patient who receives continuous enteral nutrition from a
      continuous intravenous insulin infusion to intermittent subcutaneous insulin
      therapy are discussed.

PMID- 24751552
TI  - Synthesis, pharmacological screening and in silico studies of new class of
      Diclofenac analogues as a promising anti-inflammatory agents.
AB  - A novel series of 5-[2-(2,6-dichlorophenylamino)benzyl]-3-(substituted)-1,3,4
      oxadiazol-2(3H)-thione (4a-k) derivatives have been synthesized by the Mannich
      reaction of 5-[2-(2,6-dichlorophenylamino)benzyl]-1,3,4-oxadiazol-2(3H)-thione
      (3) with an appropriately substituted primary/secondary amines, in the presence
      of formaldehyde and absolute ethanol. Structures of these novel compounds were
      characterized on the basis of physicochemical, spectral and elemental analysis.
      The title compounds (4a-k) were screened for in vivo acute anti-inflammatory and
      analgesic activities at a dose of 10mg/kg b.w. Compound 4k exhibited the most
      promising and significant anti-inflammatory profile while compounds 4a, 4d, 4e,
      4i, and 4j showed moderate to good inhibitory activity at 2nd and 4thh,
      respectively. These compounds were also found to have considerable analgesic
      activity (acetic acid induced writhing model) and antipyretic activity (yeast
      induced pyrexia model). In addition, the tested compounds were also found to
      possess less degree of ulcerogenic potential as compared to the standard NSAIDs.
      Compounds that displayed promising anti-inflammatory profile were further
      evaluated for their inhibitory activity against cyclooxygenase enzyme (COX-1/COX
      2), by colorimetric COX (ovine) inhibitor screening assay method. The results
      revealed that the compounds 4a, 4e, 4g and 4k exhibited effective inhibition
      against COX-2. In an attempt to understand the ligand-protein interactions in
      terms of the binding affinity, docking studies were performed using Molegro
      Virtual Docker (MVD-2013, 6.0) for those compounds, which showed good anti
      inflammatory activity. It was observed that the binding affinities calculated
      were in agreement with the IC50 values. 

PMID- 24751553
TI  - Exploring 5-nitrofuran derivatives against nosocomial pathogens: synthesis,
      antimicrobial activity and chemometric analysis.
AB  - The burden of nosocomial or health care-associated infection (HCAI) is increasing
      worldwide. According to the World Health Organization (WHO), it is several fold
      higher in low- and middle-income countries. Considering the multidrug-resistant
      infections, the development of new and more effective drugs is crucial. Herein,
      two series (I and II) of 5-nitrofuran derivatives were designed, synthesized and
      assayed against microorganisms, including Gram-positive and -negative bacteria,
      and fungi. The pathogens screened was directly related to either the most
      currently relevant HCAI, or to multidrug-resistant infection caused by MRSA/VRSA
      strains, for instance. The sets I and II were composed by substituted-[N'-(5
      nitrofuran-2-yl)methylene]benzhydrazide and 3-acetyl-5-(substituted-phenyl)-2-(5
      nitro-furan-2-yl)-2,3-dihydro-1,3,4-oxadiazole compounds, respectively. The
      selection of the substituent groups was based upon physicochemical properties,
      such as hydrophobicity and electronic effect. The compounds have showed better
      activity against Staphylococcus aureus, Escherichia coli, and Enterococcus
      faecalis. The findings from S. aureus strain, which was more susceptible, were
      used to investigate the intersamples and intervariables relationships by applying
      chemometric methods. It is noteworthy that the compound 4-butyl-[N'-(5-nitrofuran
      2-yl)methylene]benzhydrazide has showed similar MIC value to vancomycin, which is
      the reference drug for multidrug-resistant S. aureus infections. Taken the
      findings together, the 5-nitrofuran derivatives might be indeed considered as
      promising hits to develop novel antimicrobial drugs to fight against nosocomial
      infection. 

PMID- 24751554
TI  - Prediction of XDR/pre-XDR tuberculosis by genetic mutations among MDR cases from
      a hospital in Shandong, China.
AB  - The prevalence of extensively drug-resistant (XDR) and pre-extensively drug
      resistant (pre-XDR) tuberculosis in China highlights the need for rapid
      diagnosis. Molecular methods based on the detection of resistance-conferring
      mutations provide promising solution for rapid diagnosis. Here, we evaluated the
      accuracy of using mutations in gyrA, rrs and tlyA to predict resistance to
      levofloxacin (LEV), amikacin (AMK) and capreomycin (CAP), among 208 clinical
      multidrug-resistant (MDR) Mycobacterium tuberculosis strains collected in a local
      hospital in Shandong province, China. A total of 131 (63.0%, 131/208) strains
      were detected resistance to at least one of the 3-s line drugs by drug
      susceptible tests (DSTs). By comparing the mutation data with the phenotypic
      results, we found all mutations in three genes could specifically (with
      specificities from 93.9% to 100%) predict resistances with sensitivities of 77.8%
      for gyrA (LEV), 71.4% for rrs (AMK), 53.6% for rrs (CAP), 14.3% for tlyA (CAP),
      64.3% for rrs and tlyA (CAP). The combination of these mutations could predict
      68.9% and 63.4% pre-XDR and XDR TB, respectively. However, the positive
      predictive value of rrs for CAP resistance (57.7%) and the negative predictive
      values of gyrA for LEV resistance (74.5%) were not satisfying. Our results
      supported the use of genetic mutations to predict resistance to AMK and
      fluoroquinolones. An algorithm that combines molecular methods and traditional
      DST would be valuable for detecting resistance to second-line drugs in our
      hospital. 

PMID- 24751555
TI  - Purification of pre-miR-29 by a new O-phospho-l-tyrosine affinity chromatographic
      strategy optimized using design of experiments.
AB  - MicroRNAs are the most studied small non-coding RNA molecules that are involved
      in post-transcriptional regulation of target genes. Their role in Alzheimer's
      disease is being studied and explored in order to develop a new therapeutic
      strategy based on specific gene silencing. This disease is characterized by
      protein deposits, mainly deposits of extracellular Abeta plaques, produced upon
      endoproteolytic cleavage of APP by beta-site APP-cleaving enzyme 1 (BACE1).
      Recent studies have shown that particularly miR-29 cluster can be involved in the
      decrease of Abeta plaques production, by acting on BACE1 expression silencing. In
      order to use this microRNA as potential therapeutic it is essential to guarantee
      its purity, stability and integrity. Hence, the main purpose of this study was
      the development of a new affinity chromatographic strategy by using an O-phospho
      l-tyrosine matrix and applying Box-Behnken design (BBD) to obtain pre-miR-29 with
      high purity degree and yield, envisioning its application in gene therapy. Thus,
      after process optimization the best results were achieved with a decreasing
      ammonium sulfate gradient in 10mM Tris buffer, pH 8 (1.6M (NH4)2SO4, 1.11M
      (NH4)2SO4 and 0M (NH4)2SO4), at 16 degrees C. These experimental conditions
      allowed the recovery of pre-miR-29 with 52% of purity and 71% of recovery yield.
      The O-phospho-l-tyrosine matrix was initially chosen to mimic the natural
      interactions that occur inside the cell, and in fact it was proved a satisfactory
      selectivity for pre-miR-29. Also the innovative application of BBD for this
      strategy was efficient (R(2)=0.98 for % relative recovery and R(2)=0.93 for %
      relative purity) and essential to achieve best purification results in short
      time, saving lab resources. 

PMID- 24751556
TI  - Addition of reagents to the sheath liquid: a novel concept in capillary
      electrophoresis-mass spectrometry.
AB  - Conventional coupling of capillary electrophoresis with electrospray ionisation
      mass spectrometry typically relies on the use of a triaxial sheath-flow liquid
      interface to facilitate electrical contact and provide a stable electrospray. In
      this type of analysis, the use of additives in the sheath liquid itself can also
      be used to improve ionisation of analytes and even facilitate reactions between
      separation and detection steps (which we broadly term "sheath-flow chemistry").
      In the present work, this concept is demonstrated using two types of sheath-flow
      reactions for CE coupled with quadrupole time-of-flight (Q-TOF) MS detection.
      Sheath liquid compositions containing deuterated solvents or DPPH (2,2-diphenyl-1
      dipicrylhydrazyl) stable free-radicals yield useful additional structural
      information for separated analytes. Investigations of fundamental physical and
      chemical characteristics of the sheath liquid coupling show their direct
      influence on the efficiency and some of the products of the respective reactions.
      For example, reducing the capillary internal diameter from 75 to 25MUm increased
      the relative abundance of fully deuterated ions detected by 63-65% (5
      exchangeable hydrogens) using constant sheath-flow conditions. Addition of 0.05
      0.2mM DPPH to the sheath liquid reduced the peak total ion count obtained for
      typical antioxidant species by 20 to >95% allowing strongly antioxidant species
      from mixtures to be readily identified and further studied. The presented
      approach allows a rapid and information-rich analysis to be performed with
      minimal reagent and sample consumption. 

PMID- 24751558
TI  - Introducing the Annals of Global Health.

PMID- 24751557
TI  - High ionic strength narrows the population of sites participating in protein ion
      exchange adsorption: a single-molecule study.
AB  - The retention and elution of proteins in ion-exchange chromatography is routinely
      controlled by adjusting the mobile phase salt concentration. It has repeatedly
      been observed, as judged from adsorption isotherms, that the apparent
      heterogeneity of adsorption is lower at more-eluting, higher ionic strength.
      Here, we present an investigation into the mechanism of this phenomenon using a
      single-molecule, super-resolution imaging technique called motion-blur Points
      Accumulation for Imaging in Nanoscale Topography (mbPAINT). We observed that the
      number of functional adsorption sites was smaller at high ionic strength and that
      these sites had reduced desorption kinetic heterogeneity, and thus narrower
      predicted elution profiles, for the anion-exchange adsorption of alpha
      lactalbumin on an agarose-supported, clustered-charge ligand stationary phase.
      Explanations for the narrowing of the functional population such as inter-protein
      interactions and protein or support structural changes were investigated through
      kinetic analysis, circular dichroism spectroscopy, and microscopy of agarose
      microbeads, respectively. The results suggest the reduction of heterogeneity is
      due to both electrostatic screening between the protein and ligand and tuning the
      steric availability within the agarose support. Overall, we have shown that
      single molecule spectroscopy can aid in understanding the influence of ionic
      strength on the population of functional adsorbent sites participating in the ion
      exchange chromatographic separation of proteins. 

PMID- 24751559
TI  - Best of Mount Sinai Heart fellows symposia.

PMID- 24751560
TI  - Nurse management of hypertension in rural western Kenya: implementation research
      to optimize delivery.
AB  - BACKGROUND: Hypertension is the leading global risk factor for mortality.
      Hypertension treatment and control rates are low worldwide, and insufficient
      human resource capacity is among the contributing factors. Thus, a critical
      component of hypertension management is to develop novel and effective solutions
      to the human resources challenge. One potential solution is task redistribution
      and nurse management of hypertension in these settings. OBJECTIVES: The aim of
      this study is to investigate whether nurses can effectively reduce blood pressure
      in hypertensive patients in rural western Kenya and, by extension, throughout sub
      Saharan Africa. METHODS: An initial phase of qualitative inquiry will assess
      facilitators and barriers of nurse management of hypertension. In addition, we
      will perform usability and feasibility testing of a novel, electronic tablet
      based integrated decision-support and record-keeping tool for the nurses. An
      impact evaluation of a pilot program for nurse-based management of hypertension
      will be performed. Finally, a needs-based workforce estimation model will be used
      to estimate the nurse workforce requirements for stable, long-term treatment of
      hypertension throughout western Kenya. FINDINGS: The primary outcome measure of
      the impact evaluation will be the change in systolic blood pressure of
      hypertensive individuals assigned to nurse-based management after 1 year of
      follow-up. The workforce estimation modeling output will be the full-time
      equivalents of nurses. CONCLUSIONS: This study will provide evidence regarding
      the effectiveness of strategies to optimize task redistribution and nurse-based
      management of hypertension that can be applicable to noncommunicable disease
      management in low- and middle-income countries.

PMID- 24751562
TI  - The concept of the polypill in the prevention of cardiovascular disease.
AB  - BACKGROUND: Cardiovascular disease (CVD) is a global epidemic and the largest
      cause of noncommunicable disease-related death worldwide. The concept of a
      combination pill, or "polypill," composed of aspirin, antihypertensives, and a
      statin has been suggested to simplify and improve the prevention and treatment of
      CVD. Individually, these medications have been shown to effectively modify risk
      factors of CVD, and a single pill composed of these medications has the potential
      to conveniently and cost effectively provide additive benefits in relative risk
      reduction. In particular, the polypill concept presents significant potential for
      reducing the impact of cardiovascular disease in low- and middle-income countries
      where populations account for >80% of all CVD-related deaths worldwide. Using a
      polypill as the primary way to prevent CVD has been proposed as a broad
      "vaccination" strategy to treat asymptomatic individuals based solely on age or
      the presence of risk factors. FINDINGS: Several clinical trials have shown that
      combination pills are well tolerated and have lower relative risk by as much as
      60-70% by moderately reducing blood pressure and LDL-cholesterol. However,
      uncertainty remains in regards to long-term adherence, cost effectiveness, and
      "medicalization" of asymptomatic individuals, who account for a large percentage
      of the world's population. Furthermore, more data regarding CVD outcomes is
      required to evaluate the widespread use of a polypill in primary prevention.
      CONCLUSION: The use of a combination pill in individuals with overt CVD provides
      the potential to reduce the "treatment gap" that exists in the secondary
      prevention of CVD by simplifying treatment algorithms, reducing nonadherence, and
      improving access to medications in countries lacking adequate healthcare
      infrastructure. The promising results of completed clinical trials have lead to
      the approval of polypill formulations (e.g., Polycap, Trinomia(r), or Zycad) and
      several large clinical trials are posed to present new data regarding outcomes
      and adherence.

PMID- 24751563
TI  - Management of hypertrophic cardiomyopathy.
AB  - BACKGROUND: Hypertrophic cardiomyopathy (HCM) is clinically defined as
      unexplained myocardial hypertrophy, and it is an autosomal dominant disease of
      the cardiac sarcomere. It is present in 1 in 500 in the general adult population,
      making it the most common genetic cardiovascular disease. The pathophysiology of
      HCM is complex, leading to significant variability in clinical presentation.
      This, combined with the lack of randomized trials, makes the management of these
      patients difficult. FINDINGS: The majority of patients with HCM are asymptomatic
      without a substantial reduction in survival. However, a considerable portion of
      patients will experience significant symptoms and HCM-related death, and
      effective therapies are available for these patients. Patients may have symptoms
      of heart failure from outflow tract obstruction and/or restrictive physiology.
      Medical therapy targeted at the underlying pathophysiology should be used, and
      surgical myectomy or alcohol septal ablation is available for those with
      refractory symptoms. While the overall risk of sudden cardiac death (SCD) is low
      in HCM patients, some are at elevated risk for and experience SCD, a devastating
      outcome in young patients. Risk stratification for SCD and treatment with
      implantable cardioverter-defibrillators is paramount. Many HCM patients will also
      develop atrial fibrillation, and this is often poorly tolerated. A rhythm control
      strategy with antiarrhythmic drugs or catheter ablation is often necessary, and
      anticoagulation should be administered to reduce the risk of thromboembolism.
      Finally, family members of patients with HCM should be regularly screened with
      electrocardiography and echocardiography. CONCLUSIONS: HCM is a complex disease
      with heterogeneous phenotypes and clinical manifestations. The management of HCM
      focuses on reducing symptoms of heart failure, preventing SCD, treating atrial
      fibrillation, and screening family members. Treatment should be tailored to the
      unique characteristics of each individual patient.

PMID- 24751564
TI  - Management of chronic heart failure: biomarkers, monitors, and disease management
      programs.
AB  - BACKGROUND: The management of patients with heart failure has been evolving given
      the complex nature of the disease and the increasing number of patients.
      FINDINGS: Biomarkers, and in particular the natriuretic peptides, have been
      studied to assist with diagnosis, chronic management, and prognosis in patients
      with heart failure. Several new biomarkers are emerging and may be used
      individually or in combination with the natriuretic peptides. The use of cardiac
      monitoring devices and disease management programs is being established to assist
      in the care of patients with chronic heart failure. Interventions using phone
      calls, telemedicine devices, intracardiac pressure monitors, and implantable
      cardioverter defibrillators have been investigated. CONCLUSIONS: The combination
      of biomarkers, monitoring devices, and disease management programs shows promise
      for improving care in this challenging patient population.

PMID- 24751561
TI  - Regression of atherosclerosis: insights from animal and clinical studies.
AB  - BACKGROUND: Based on studies that date back to the 1920s, regression and
      stabilization of atherosclerosis in humans has gone from just a dream to one that
      is achievable. Review of the literature indicates that the successful attempts at
      regression generally applied robust measures to improve plasma lipoprotein
      profiles. Examples include extensive lowering of plasma concentrations of
      atherogenic apolipoprotein B and enhancement of reverse cholesterol transport
      from atheromata to the liver. FINDINGS: Possible mechanisms responsible for
      lesion shrinkage include decreased retention of atherogenic apolipoprotein B
      within the arterial wall, efflux of cholesterol and other toxic lipids from
      plaques, emigration of lesional foam cells out of the arterial wall, and influx
      of healthy phagocytes that remove necrotic debris as well as other components of
      the plaque. This review will highlight the role key players such as LXR, HDL and
      CCR7 have in mediating regression. CONCLUSION: Although much progress has been
      made, there are many unanswered questions. There is, therefore, a clear need for
      preclinical and clinical testing of new agents expected to facilitate
      atherosclerosis regression with the hope that additional mechanistic insights
      will allow further progress.

PMID- 24751565
TI  - Myocardial recovery and the failing heart: medical, device and mechanical
      methods.
AB  - BACKGROUND: Cardiac remodeling describes the molecular, cellular, and
      interstitial changes that cause the ventricle to develop pathologic geometry as
      heart failure progresses. Reverse remodeling, or the healing of a failing heart,
      leads to improved mortality and quality of life. FINDINGS: Therapies that lead to
      reverse remodeling include medications such as beta-blockers and angiotensin
      converting enzyme inhibitors; cardiac resynchronization therapy with
      biventricular pacing; and mechanical support with left ventricular assist
      devices. CONCLUSIONS: Further study is needed to better predict which patients
      will benefit most from these therapies and will then go on to experience reverse
      remodeling and myocardial recovery.

PMID- 24751566
TI  - Cardiac resynchronization therapy: who benefits?
AB  - BACKGROUND: Cardiac resynchronization therapy (CRT) has been well established in
      multiple large trials to improve symptoms, hospitalizations, reverse remodeling,
      and mortality in well-selected patients with heart failure when used in addition
      to optimal medical therapy. Updated consensus guidelines outline patients in whom
      such therapy is most likely to result in substantial benefit. However, pooled
      data have demonstrated that only approximately 70% of patients who qualify for
      CRT based on current indications actually respond favorably. In addition, current
      guidelines are based on outcomes from the carefully selected patients enrolled in
      clinical trials, and almost certainly fail to include all patients who might
      benefit from CRT. FINDINGS: The identification of patients most likely to benefit
      from CRT requires consideration of factors beyond these standard criteria, QRS
      morphology with particular consideration in patients with left bundle-branch
      block pattern, extent of QRS prolongation, etiology of cardiomyopathy, rhythm,
      and whether the patient requires or will eventually need antibradycardia pacing.
      In addition, the baseline severity of functional impairment may influence the
      type of benefit to be expected from CRT; for example, New York Heart Association
      class I patients may derive long-term benefit in cardiac structure and function,
      but no benefit in symptoms or hospitalizations can be reasonably expected. In
      contrast, certain New York Heart Association class IV patients may be too sick to
      realize long-term mortality benefits from CRT, but improvements in hemodynamic
      profile and functional capacity may represent vital advances in this population.
      CONCLUSION: This review evaluates the evidence regarding the various factors that
      can predict positive or even detrimental responses to CRT, to help better
      determine who benefits most from this evolving therapy.

PMID- 24751567
TI  - Cardiovascular pathophysiology in chronic kidney disease: opportunities to
      transition from disease to health.
AB  - BACKGROUND: Chronic kidney disease (CKD) is common, and is associated with a high
      burden of cardiovascular disease. This cardiovascular risk is incompletely
      explained by traditional risk factors, calling attention to a need to better
      understand the pathways in CKD contributing to adverse cardiovascular outcomes.
      FINDINGS: Pathophysiological derangements associated with CKD, including
      disordered sodium, potassium, and water homeostasis, renin-angiotensin
      aldosterone and sympathetic activity, anemia, bone and mineral metabolism,
      uremia, and toxin accumulation may contribute directly to progression of
      cardiovascular disease and adverse outcomes. CONCLUSION: Improving cardiovascular
      health in patients with CKD requires improved understanding of renocardiac
      pathophysiology. Ultimately, the most successful strategy may be prevention of
      incident CKD itself.

PMID- 24751568
TI  - Transthoracic echocardiography and 6-minute walk test in Kuwaiti sickle cell
      disease patients.
AB  - OBJECTIVE: The aim of this study was to investigate cardiac abnormalities in
      Kuwaiti sickle cell disease (SCD) patients using markers such as tricuspid
      regurgitant jet velocity (TRJV), pulmonary artery systolic pressure (PASP), and
      the 6-minute walk (6MW) test and correlate these findings with clinical,
      hematological, and biochemical parameters. MATERIALS AND METHODS: Seventy-three
      patients with SCD and 70 matched controls were studied. The cardiac status was
      investigated using transthoracic echocardiography in 57 patients; the 6MW test
      was carried out in patients and controls. Complete blood counts and hemolytic
      parameters were assessed. RESULTS: Reticulocytes, bilirubin, and lactate
      dehydrogenase were significantly higher (p < 0.0001) in patients, while
      hemoglobin (Hb) and haptoglobin were lower (p < 0.0001) than in controls. The
      mean fetal Hb among patients was 15.85 +/- 8.7%. Of the 57 patients, 14 (24.5%)
      and 15 (26%) had mild tricuspid and mitral regurgitation, respectively. The mean
      ejection fraction, TRJV, and PASP were 63.9 +/- 6.3%, 1.7 +/- 0.5 m/s, and 23.0
      +/- 7.3 mm Hg, respectively. Three (5.2%) patients had mildly raised TRJV (2.6
      2.97 m/s, normal range <2.5 m/s) while 8 (14%) had high PASP (mean 35.3 +/- 5.1
      mm Hg, normal range <30 mm Hg). Hb, hematocrit, and reticulocytes were different
      (p = 0.010, p = 0.006, and p = 0.011, respectively) between patients with normal
      and high PASP. All 3 patients who had a high TRJV had a high PASP, and 2 of these
      patients died during follow-up. The systolic and diastolic blood pressure, oxygen
      saturation before and after the 6MW test, and distance walked were lower (p =
      0.006, p = 0.000, p = 0.002, p = 0.000, and p = 0.000, respectively) in patients
      compared to controls. CONCLUSION: Raised PASP was common in Kuwaiti SCD patients
      while raised TRJV was not.

PMID- 24751571
TI  - Neural correlates of inferring speaker sincerity from white lies: an event
      related potential source localization study.
AB  - During social interactions, listeners weigh the importance of linguistic and
      extra-linguistic speech cues (prosody) to infer the true intentions of the
      speaker in reference to what is actually said. In this study, we investigated
      what brain processes allow listeners to detect when a spoken compliment is meant
      to be sincere (true compliment) or not ("white lie"). Electroencephalograms of 29
      participants were recorded while they listened to Question-Response pairs, where
      the response was expressed in either a sincere or insincere tone (e.g., "So, what
      did you think of my presentation?"/"I found it really interesting.").
      Participants judged whether the response was sincere or not. Behavioral results
      showed that prosody could be effectively used to discern the intended sincerity
      of compliments. Analysis of temporal and spatial characteristics of event-related
      potentials (P200, N400, P600) uncovered significant effects of prosody on P600
      amplitudes, which were greater in response to sincere versus insincere
      compliments. Using low resolution brain electromagnetic tomography (LORETA), we
      determined that the anatomical sources of this activity were likely located in
      the (left) insula, consistent with previous reports of insular activity in the
      perception of lies and concealments. These data extend knowledge of the
      neurocognitive mechanisms that permit context-appropriate inferences about
      speaker feelings and intentions during interpersonal communication. 

PMID- 24751569
TI  - Inhibitory and excitatory amino acid neurotransmitters are utilized by the
      projection from the dorsal deep mesencephalic nucleus to the sublaterodorsal
      nucleus REM sleep induction zone.
AB  - The sublaterodorsal nucleus (SLD) in the pons of the rat is a locus supporting
      short-latency induction of a REM sleep-like state following local application of
      a GABAA receptor antagonist or kainate, glutamate receptor agonist. One
      putatively relevant source of these neurotransmitters is from the region of the
      deep mesencephalic nucleus (DpMe) just ventrolateral to the periaquiductal gray,
      termed the dorsal DpMe (dDpMe). Here, the amino acid neurotransmitter innervation
      of SLD from dDpMe was studied utilizing anterograde tract-tracing with
      biotinylated dextranamine (BDA) and fluorescence immunohistochemistry visualized
      with laser scanning confocal microscopy. Both markers for inhibitory and
      excitatory amino acid neurotransmitters were found in varicose axon fibers in SLD
      originating from dDpMe. Vesicular glutamate transporter2 (VGLUT2) represented the
      largest number of anterogradely labeled varicosities followed by vesicular GABA
      transporter (VGAT). Numerous VGAT and VGLUT2 labeled varicosities were observed
      apposed to dDpMe-labeled axon fibers indicating both excitatory and inhibitory
      presynaptic, local modulation within the SLD. Some double-labeled BDA/VGAT
      varicosities were seen apposed to small somata labeled for glutamate consistent
      with being presynaptic to the phenotype of REM sleep-active SLD neurons. Results
      found support the current theoretical framework of the interaction of dDpMe and
      SLD in control of REM sleep, while also indicating operation of mechanisms with a
      greater level of complexity. 

PMID- 24751570
TI  - Do not think about pain: neural correlates of attention guiding during visual
      symptom provocation in dental phobia--an fMRI study.
AB  - Patients undergoing dental treatment employ different attentional strategies. In
      order to investigate associated neuronal correlates, we exposed 20 women
      suffering from dental phobia and 20 non-anxious women to disorder-related and
      unrelated pictures. They were asked to either direct their attention to a
      foreground stimulus in the image (distraction), to classify the content, or to
      judge whether the picture elicited fear of pain. The patients rated the majority
      of dental pictures as pain-relevant (84%) in contrast to the control group (12%).
      Observed group differences were restricted to the pain condition with enhanced
      orbitofrontal cortex (OFC) activation displayed by the patients. For the
      controls, OFC and amygdala activity were positively correlated with self-reported
      dental anxiety during attention to pain. Across both groups, pain focusing
      provoked increased amygdala recruitment. As the OFC and amygdala are central for
      the evaluation of threat signals, the mere thinking about the possible pain
      relevance of stimuli seems to be dysfunctional.

PMID- 24751572
TI  - Prolactin-sensitive neurons express estrogen receptor-alpha and depend on sex
      hormones for normal responsiveness to prolactin.
AB  - Estrogens and prolactin share important target tissues, including the gonads,
      brain, liver, kidneys and some types of cancer cells. Herein, we sought
      anatomical and functional evidence of possible crosstalk between prolactin and
      estrogens in the mouse brain. First, we determined the distribution of prolactin
      responsive neurons that express the estrogen receptor alpha (ERalpha). A large
      number of prolactin-induced pSTAT5-immunoreactive neurons expressing ERalpha mRNA
      were observed in several brain areas, including the anteroventral periventricular
      nucleus, medial preoptic nucleus, arcuate nucleus of the hypothalamus,
      ventrolateral subdivision of the ventromedial nucleus of the hypothalamus (VMH),
      medial nucleus of the amygdala and nucleus of the solitary tract. However,
      although the medial preoptic area, periventricular nucleus of the hypothalamus,
      paraventricular nucleus of the hypothalamus, retrochiasmatic area, dorsomedial
      subdivision of the VMH, lateral hypothalamic area, dorsomedial nucleus of the
      hypothalamus and ventral premammillary nucleus contained significant numbers of
      prolactin-responsive neurons, these areas showed very few pSTAT5-immunoreactive
      cells expressing ERalpha mRNA. Second, we evaluated prolactin sensitivity in
      ovariectomized mice and observed that sex hormones are required for a normal
      responsiveness to prolactin as ovariectomized mice showed a lower number of
      prolactin-induced pSTAT5 immunoreactive neurons in all analyzed brain nuclei
      compared to gonad-intact females. In addition, we performed hypothalamic gene
      expression analyses to determine possible post-ovariectomy changes in components
      of prolactin signaling. We observed no significant changes in the mRNA expression
      of prolactin receptor, STAT5a or STAT5b. In summary, sex hormones exert a
      permissive role in maintaining the brain's prolactin sensitivity, most likely
      through post-transcriptional mechanisms.

PMID- 24751573
TI  - Cerebellar afferents originating from the medullary reticular formation that are
      different from mossy, climbing or monoaminergic fibers in the rat.
AB  - Integration of cortical Purkinje cell inputs and brain stem inputs is essential
      in generating cerebellar outputs to the cerebellar nuclei (CN). Currently,
      collaterals of climbing and mossy fiber axons, noradrenergic, serotoninergic and
      cholinergic axons, and collaterals of rubrospinal axons are known to innervate
      the CN from the brain stem. We investigated whether other afferents to the CN
      from the medulla exist in the rat. Retrograde labeling revealed the presence of
      neurons that project to the CN but not to the cerebellar cortex in the median
      reticular formation in the rostrodorsal medulla (tentatively named 'caudal raphe
      interpositus area', CRI). Anterograde tracer injection into the CRI labeled
      abundant axonal terminals in the CN, mainly in the ventral parvocellular part of
      the posterior interposed and lateral nucleus. Axonal reconstruction showed that a
      single CRI axon projected to the CN with 170-1086 varicosities, more broadly and
      densely than collaterals of a mossy or climbing fiber axon. CRI axons had no or a
      few collaterals that projected to the granular and Purkinje cell layers of the
      cerebellar cortex with some small terminals, indicating that these axons are
      different from mossy fiber axons. CRI axons also had collaterals that projected
      to the medial vestibular nucleus and an ascending branch that was not
      reconstructed. The location of the CRI, electron microscopic observations, and
      immunostaining results all indicated that CRI axons are not monoaminergic. We
      conclude that CRI axons form a type of afferent projection to the CN that is
      different from mossy, climbing or monoaminergic fibers. 

PMID- 24751574
TI  - Comparative metabolism of furan in rodent and human cryopreserved hepatocytes.
AB  - Furan is a liver toxicant and carcinogen in rodents. Although humans are most
      likely exposed to furan through a variety of sources, the effect of furan
      exposure on human health is still unknown. In rodents, furan requires metabolism
      to exert its toxic effects. The initial product of the cytochrome P450 2E1
      catalyzed oxidation is a reactive alpha,beta-unsaturated dialdehyde, cis-2-butene
      1,4-dial (BDA). BDA is toxic and mutagenic and consequently is considered
      responsible for the toxic effects of furan. The urinary metabolites of furan in
      rats are derived from the reaction of BDA with cellular nucleophiles, and
      precursors to these metabolites are detected in furan-exposed hepatocytes. Many
      of these precursors are 2-(S-glutathionyl)butanedial-amine cross-links in which
      the amines are amino acids and polyamines. Because these metabolites are derived
      from the reaction of BDA with cellular nucleophiles, their levels are a measure
      of the internal dose of this reactive metabolite. To compare the ability of human
      hepatocytes to convert furan to the same metabolites as rodent hepatocytes, furan
      was incubated with cryopreserved human and rodent hepatocytes. A semiquantitative
      liquid chromatography with tandem mass spectrometry assay was developed for a
      number of the previously characterized furan metabolites. Qualitative and
      semiquantitative analysis of the metabolites demonstrated that furan is
      metabolized in a similar manner in all three species. These results indicate that
      humans may be susceptible to the toxic effects of furan. 

PMID- 24751575
TI  - Screening of specific inhibitors for human carboxylesterases or arylacetamide
      deacetylase.
AB  - Esterases catalyze the hydrolysis of therapeutic drugs containing esters or
      amides in their structures. Human carboxylesterase (CES) and arylacetamide
      deacetylase (AADAC) are the major enzymes that catalyze the hydrolysis of drugs
      in the liver. Characterization of the enzyme(s) responsible for drug metabolism
      is required in drug development and to realize optimal drug therapy. Because
      multiple enzymes may show a metabolic potency for a given compound, inhibition
      studies using chemical inhibitors are useful tools to determine the contribution
      of each enzyme in human tissue preparations. The purpose of this study was to
      find specific inhibitors for human CES1, CES2, and AADAC. We screened 542
      chemicals for the inhibition potency toward hydrolase activities of p-nitrophenyl
      acetate by recombinant CES1, CES2, and AADAC. We found that digitonin and
      telmisartan specifically inhibited CES1 and CES2 enzyme activity, respectively.
      Vinblastine potently inhibited both AADAC and CES2, but no specific inhibitor of
      AADAC was found. The inhibitory potency and specificity of these compounds were
      also evaluated by monitoring the effects on hydrolase activity of probe compounds
      of each enzyme (CES1: lidocaine, CES2: CPT-11, AADAC: phenacetin) in human liver
      microsomes. Telmisartan and vinblastine strongly inhibited the hydrolysis of CPT
      11 and/or phenacetin, but digitonin did not strongly inhibit the hydrolysis of
      lidocaine, indicating that the inhibitory potency of digitonin was different
      between recombinant CES1 and liver microsomes. Although we could not find a
      specific inhibitor of AADAC, the combined use of telmisartan and vinblastine
      could predict the responsibility of human AADAC to drug hydrolysis. 

PMID- 24751576
TI  - Deletion of the CAP10 gene of Cryptococcus neoformans results in a pleiotropic
      phenotype with changes in expression of virulence factors.
AB  - The human pathogen Cryptococcus neoformans causes meningo-encephalitis. The
      polysaccharide capsule is an important virulence factor for this yeast-like
      fungus. Previously, we had shown that disruption of the CAP10 gene, encoding a
      putative xylosyltransferase, results in mutant cells that lack most of the
      capsular polysaccharides on the cell surface, but do not show a typical acapsular
      phenotype. In contrast to the acapsular cap59 mutant, cap10 did not induce
      maturation of dendritic cells when exposed to components of the immune system. In
      order to gain further insight into the causes of this phenotype displayed by the
      cap10 mutant, we performed a more in-depth phenotypic analysis of the cell wall
      and surface structures of this mutant compared to the wild type strain and
      acapsular mutant cap59. Moreover, we analyzed the cap10 mutant and the wild type
      strain for differential gene expression of, amongst others, enzymes that are
      involved in biogenesis of cell wall and capsule components. We conclude that a
      mutation in the CAP10 gene results in a pleiotropic phenotype with effects on
      different cellular processes affecting, amongst others, cell size, expression of
      virulence factors and size of extracellular vesicles. 

PMID- 24751577
TI  - Scanning ion microscopy with low energy lithium ions.
AB  - Using an ion source based on photoionization of laser-cooled lithium atoms, we
      have developed a scanning ion microscope with probe sizes of a few tens of
      nanometers and beam energies from 500eV to 5keV. These beam energies are much
      lower than the typical operating energies of the helium ion microscope or gallium
      focused ion beam systems. We demonstrate how low energy can be advantageous in
      ion microscopy when detecting backscattered ions, due to a decreased interaction
      volume and the potential for surface sensitive composition analysis. As an
      example application that demonstrates these advantages, we non-destructively
      image the removal of a thin residual resist layer during plasma etching in a nano
      imprint lithography process. 

PMID- 24751579
TI  - Analyzing the human microbiome: a "how to" guide for physicians.
AB  - The application of high-throughput next-generation sequencing to the analysis of
      the human microbiome has led to a shift in our understanding of the etiology of
      complex diseases. In consequence, a great deal of literature can now be found
      exploring this complex system, and reviewing recent findings. Observations of
      alterations in the intestinal microbiome associating with inflammatory bowel
      disease and other chronic conditions are well supported and have been widely
      accepted by the research community. Yet, it can be difficult to objectively
      evaluate the importance of these results, given the wide variety of methodologies
      applied by different groups in the field. The aim of this review is to focus
      attention on the basic principles involved in microbiome analyses, and to
      describe factors that may have an impact on the accurate interpretation of
      results. 

PMID- 24751578
TI  - An analysis of the global expression of microRNAs in an experimental model of
      physiological left ventricular hypertrophy.
AB  - BACKGROUND: MicroRNAs (miRs) are a class of small non-coding RNAs that regulate
      gene expression. Studies of transgenic mouse models have indicated that
      deregulation of a single miR can induce pathological cardiac hypertrophy and
      cardiac failure. The roles of miRs in the genesis of physiological left
      ventricular hypertrophy (LVH), however, are not well understood. OBJECTIVE: To
      evaluate the global miR expression in an experimental model of exercise-induced
      LVH. METHODS: Male Balb/c mice were divided into sedentary (SED) and exercise
      (EXE) groups. Voluntary exercise was performed on an odometer-monitored metal
      wheels for 35 days. Various tests were performed after 7 and 35 days of training,
      including a transthoracic echocardiography, a maximal exercise test, a miR
      microarray (miRBase v.16) and qRT-PCR analysis. RESULTS: The ratio between the
      left ventricular weight and body weight was increased by 7% in the EXE group at
      day 7 (p<0.01) and by 11% at day 35 of training (p<0.001). After 7 days of
      training, the microarray identified 35 miRs that were differentially expressed
      between the two groups: 20 were up-regulated and 15 were down-regulated in the
      EXE group compared with the SED group (p = 0.01). At day 35 of training, 25 miRs
      were differentially expressed: 15 were up-regulated and 10 were decreased in the
      EXE animals compared with the SED animals (p<0.01). The qRT-PCR analysis
      demonstrated an increase in miR-150 levels after 35 days and a decrease in miR
      26b, miR-27a and miR-143 after 7 days of voluntary exercise. CONCLUSIONS: We have
      identified new miRs that can modulate physiological cardiac hypertrophy,
      particularly miR-26b, -150, -27a and -143. Our data also indicate that previously
      established regulatory gene pathways involved in pathological LVH are not changed
      in physiological LVH.

PMID- 24751581
TI  - Detection of colorectal adenoma by narrow band imaging (HQ190) vs. high
      definition white light colonoscopy: a randomized controlled trial.
AB  - OBJECTIVES: The benefits of narrow band imaging (NBI) on enhancing colorectal
      adenoma detection remain questionable. We tested whether the new generation of
      NBI (190-NBI), which is twice as bright as the previous version, would improve
      adenoma detection when compared with high-definition white light (HD-WL)
      colonoscopy. METHODS: It was a randomized controlled trial with tandem
      colonoscopy. We recruited patients who underwent colonoscopy for symptoms,
      screening, or surveillance. Patients were randomized for the use of either 190
      NBI or HD-WL on withdrawal. Tandem colonoscopy was performed by using the same
      assigned colonoscope and withdrawal method. Lesions detected on first-pass and
      second-pass examination were used for adenoma detection and miss rates,
      respectively. The primary outcomes were adenoma and polyp detection rates.
      RESULTS: A total of 360 patients were randomized to undergo either 190-NBI or HD
      WL colonoscopy. Both the adenoma and polyp detection rates were significantly
      higher in the 190-NBI group compared with the HD-WL group (adenoma: 48.3% vs.
      34.4%, P=0.01; polyps: 61.1% vs. 48.3%, P=0.02). The mean number of polyps
      detected per patient was higher in the 190-NBI group (1.49% vs. 1.13, P=0.07).
      There was no significant difference in the adenoma miss rates between the two
      groups (21.8% vs. 21.2%). Multivariate analysis showed that the use of 190-NBI
      (odds ratio (OR) 1.85; 95% confidence interval (CI) 1.10-3.12), withdrawal time
      (OR 1.29; CI 1.19-1.38), patient's age (OR 1.04; CI 1.01-1.06), and male gender
      (OR 2.38; CI 1.42-3.99) were associated with adenoma detection. CONCLUSIONS: 190
      NBI colonoscopy was superior to the conventional HD-WL in detecting colorectal
      adenomas or polyps, but there was no significant difference in adenoma miss
      rates.

PMID- 24751580
TI  - Usefulness of non-magnifying narrow-band imaging in screening of early esophageal
      squamous cell carcinoma: a prospective comparative study using propensity score
      matching.
AB  - OBJECTIVES: The usefulness of non-magnifying endoscopy with narrow-band imaging
      (NBI; NM-NBI) in the screening of early esophageal squamous cell carcinoma (SCC)
      and high-grade intraepithelial neoplasia (HGIN) remains unclear. Here, we aimed
      to compare NM-NBI and chromoendoscopy with iodine staining (CE-Iodine) in terms
      of the diagnostic performance, and to evaluate the usefulness of NM-NBI in
      detecting early esophageal SCC. METHODS: We prospectively enrolled 202
      consecutive patients (male/female=180/22; median age, 67 years) with high-risk
      factors for esophageal SCC. All patients received endoscopic examination with NM
      NBI and CE-Iodine to screen for early esophageal SCC or HGIN. We conducted the
      examinations sequentially, and calculated the accuracy, sensitivity, and
      specificity through a per-lesion-based analysis. A propensity score matching
      analysis was performed to reduce the effects of selection bias, and we compared
      the respective outcomes according to NM-NBI and CE-Iodine after matching.
      RESULTS: The accuracy, sensitivity, and specificity of NM-NBI were 77.0, 88.3,
      and 75.2%, respectively, and those for unstained areas by CE-Iodine were 68.0,
      94.2, and 64.0, respectively. The accuracy and specificity of NM-NBI were
      superior to those of CE-Iodine (P=0.03 and P=0.01, respectively). However, the
      sensitivity did not significantly differ between NM-NBI and CE-Iodine (P=0.67).
      The accuracy and specificity of NM-NBI before matching were superior to those of
      CE-Iodine after matching (P=0.04 and P=0.03). CONCLUSIONS: NM-NBI was useful and
      reliable for the diagnosis of esophageal SCC and can be a promising screening
      strategy for early esophageal SCC.

PMID- 24751582
TI  - The synergistic effects of alcohol and tobacco consumption on the risk of
      esophageal squamous cell carcinoma: a meta-analysis.
AB  - OBJECTIVES: Tobacco and alcohol use are established risk factors for esophageal
      squamous cell carcinoma (ESCC). We sought to determine whether these factors act
      synergistically to increase the risk of ESCC. METHODS: We performed a systematic
      literature search in multiple electronic databases regardless of language.
      Eligible studies were population-based case-control or cohort studies of ESCC
      that assessed the effects of tobacco and/or alcohol. Departures from
      multiplicative effects were quantified by the synergy factor (SF); SF >1
      indicates positive synergy. Meta-analyses were performed to estimate summary
      adjusted odds ratios (ORs) and the summary crude SF using random-effect models.
      Heterogeneity was defined by Cochrane's Q P<0.10 and the inconsistency index.
      RESULTS: Systematic review identified 7,629 unique citations, of which 5 were
      eligible. Either tobacco or alcohol use was associated with a 20-30% increased
      risk for ESCC compared with nonuse, but the use of both was associated with an
      approximately threefold risk for ESCC; the summary-adjusted OR for combined
      alcohol and tobacco use was 3.28 (95% confidence interval (CI)=2.11, 508;
      Cochrane's Q P value=0.05; I(2)=55.3%). The summary SF for ever-use of both
      tobacco and alcohol was 1.85 (95% CI=1.45, 2.38; Cochrane's Q P value=0.49;
      I(2)=0.0%). CONCLUSIONS: There is a positive synergistic effect of alcohol and
      tobacco use for ESCC. The observed combined effect of the two factors is almost
      double if there were no synergy. Efforts for controlling the burden of ESCC
      should focus on individuals who use both alcohol and tobacco.

PMID- 24751584
TI  - Corneal collagen crosslinking: a systematic review.
AB  - Keratoconus (KCN) is an ectatic disorder with progressive corneal thinning and a
      clinical picture of corneal protrusion, progressive irregular astigmatism,
      corneal fibrosis and visual deterioration. Other ectatic corneal disorders
      include: post-LASIK ectasia (PLE) and pellucid marginal degeneration (PMD).
      Corneal crosslinking (CXL) is a procedure whereby riboflavin sensitization with
      ultraviolet A radiation induces stromal crosslinks. This alters corneal
      biomechanics, causing an increase in corneal stiffness. In recent years, CXL has
      been an established treatment for the arrest of KCN, PLE and PMD progression. CXL
      has also been shown to be effective in the treatment of corneal infections,
      chemical burns, bullous keratopathy and other forms of corneal edema. This is a
      current review of CXL - its biomechanical principles, the evolution of CXL
      protocols in the past, present and future, indications for treatment, treatment
      efficacy and safety.

PMID- 24751585
TI  - Alzheimer's and Parkinson's diseases: an environmental proteomic point of view.
AB  - Alzheimer's and Parkinson's diseases are severe neurodegenerative conditions
      triggered by complex biochemical routes. Many groups are currently pursuing the
      search for valuable biomarkers to either perform early diagnostic or to follow
      the disease's progress. Several studies have reported relevant findings regarding
      environmental issues and the progression of such diseases. Here the etiology and
      mechanisms of these diseases are briefly reviewed. Approaches that might reveal
      candidate biomarkers and environmental stressors associated to the diseases were
      analyzed under a proteomic perspective. This article is part of a Special Issue
      entitled: Environmental and structural proteomics. 

PMID- 24751586
TI  - Proteomics and integrative genomics for unraveling the mysteries of
      spermatogenesis: the strategies of a team.
AB  - The strikingly complex structural organization of the mammalian testis in vivo
      creates particular difficulties for studies of its organization, function and
      regulation. These difficulties are particularly pronounced for investigations of
      the molecular communication networks within the seminiferous tubules that govern
      spermatogenesis. The use of classical molecular and cell biology approaches to
      unravel this complexity has proved problematic, due to difficulties in
      maintaining differentiated germ cells in vitro, in particular. The lack of a
      suitable testing ground has led to a greater reliance on high-quality proteomic
      and genomic analyses as a prelude to the in vitro antx1d in vivo testing of
      hypotheses. In this study, we highlight the options currently available for
      research, as used in our laboratory, in which proteomic and integrative genomic
      strategies are applied to the study of spermatogenesis in mammals. We will
      comment on results providing insight into the molecular mechanisms underlying
      normal and pathological spermatogenesis and new perspectives for the treatment of
      male infertility in humans. Finally, we will discuss the relevance of our
      strategies and the unexpected potential and perspectives they offer to teams
      involved in the study of male reproduction, within the framework of the Human
      Proteome Project. SIGNIFICANCE: Integrative genomics is becoming a powerful
      strategy for discovering the biological significance hidden in proteomic
      datasets. This work introduces some of the integrative genomic concepts and works
      used by our team to gain new insight into mammalian spermatogenesis, a remarkably
      sophisticated process. We demonstrate the relevance of these integrative
      approaches to understand the cellular cross talks established between the somatic
      Sertoli cells and the germ cell lineage, within the seminiferous epithelium. Our
      work also contributes to new knowledge on the pathophysiology of testicular
      function, with promising clinical applications. This article is part of a Special
      Issue entitled: 20years of Proteomics in memory of Viatliano Pallini. Guest
      Editors: Luca Bini, Juan J. Calvete, Natacha Turck, Denis Hochstrasser and Jean
      Charles Sanchez.

PMID- 24751587
TI  - Biomimicry of multifunctional nanostructures in the neck feathers of mallard
      (Anas platyrhynchos L.) drakes.
AB  - Biological systems serve as fundamental sources of inspiration for the
      development of artificially colored devices, and their investigation provides a
      great number of photonic design opportunities. While several successful
      biomimetic designs have been detailed in the literature, conventional fabrication
      techniques nonetheless remain inferior to their natural counterparts in
      complexity, ease of production and material economy. Here, we investigate the
      iridescent neck feathers of Anas platyrhynchos drakes, show that they feature an
      unusual arrangement of two-dimensional (2D) photonic crystals and further exhibit
      a superhydrophobic surface, and mimic this multifunctional structure using a
      nanostructure composite fabricated by a recently developed top-down iterative
      size reduction method, which avoids the above-mentioned fabrication challenges,
      provides macroscale control and enhances hydrophobicity through the surface
      structure. Our 2D solid core photonic crystal fibres strongly resemble drake neck
      plumage in structure and fully polymeric material composition, and can be
      produced in wide array of colors by minor alterations during the size reduction
      process. 

PMID- 24751588
TI  - Structures at risk with medial double hindfoot fusion: a cadaveric study.
AB  - Although discussed as an alternative to triple arthrodesis for hindfoot
      correction, the published data surrounding the medial double arthrodesis, or
      fusion of the subtalar and talonavicular joints, has not addressed the proximity
      of the anatomic structures at risk. A total of 10 cadaver specimens were used to
      examine the risk of damage to the neurovascular and tendinous structures of the
      posterior medial hindfoot when performing the medial double arthrodesis. The
      distance of the reviewed structures was measured in relation to the standardized
      point of the middle facet of the calcaneus (mean +/- standard deviation and
      range). The proximity of the middle facet to the posterior tibial tendon was 1.88
      +/- 2.65 (range 0 to 6.65) mm, to the flexor digitorum longus tendon was 5.34 +/-
      4.79 (range -3.14 to 12.79) mm, to the flexor hallucis longus tendon was 19.08 +/
      4.84 (range 13.04 to 27.31) mm, and to the neurovascular bundle was 21.19 +/-
      7.84 (range 8.36 to 34.26) mm. At the level of the middle facet, the posterior
      tibial tendon was the largest tendon, measuring 7.14 +/- 2.21 (range 3.31 to
      10.23) mm by 2.95 +/- 0.88 mm (range 1.86 to 4.24 mm; area 22.37 +/- 12.23 mm(2),
      range 6.16 to 43.38 mm) followed by the flexor digitorum longus tendon at 4.25 +/
      1.25 (range 1.74 to 5.95) mm by 2.25 +/- 0.96 mm (range 1.41 to 4.79 mm; area
      8.88 +/- 2.62 mm(2), range 6.12 to 14.52 mm) and flexor hallucis longus tendon at
      5.75 +/- 2.05 (range 2.27 to 8.91) mm by 2.75 +/- 0.82 mm (range 1.35 to 4.13 mm;
      area 16.81 +/- 10.05 mm(2), range 4.81 to 36.80 mm). During dissection for the
      medial double arthrodesis, one can encounter critical anatomic structures,
      including artery, vein, nerve, and tendon. Our cadaveric investigation found a
      mean safe distance of more than 2 cm between the middle facet of the
      talocalcaneal articulation and the inferiorly located neurovascular bundle using
      the medial double arthrodesis approach.

PMID- 24751589
TI  - Subungual glomus cell proliferation in the toe: a case report.
AB  - Glomus tumors are rare benign neoplasms. They typically present with a triad of
      severe pain, point tenderness, and cold sensitivity. Most glomus tumors will form
      well-circumscribed nodules, and excisional biopsy of masses detected by
      ultrasonography or magnetic resonance imaging of the lesion can relieve the
      symptoms. We describe a 30-year-old female patient with nontumorous glomus cell
      proliferation with clinical symptoms similar to those of glomus tumors. The
      lesion was treated by exploration and excision, with a satisfactory clinical
      outcome. 

PMID- 24751590
TI  - Origin and distribution of rare earth elements in various lichen and moss species
      over the last century in France.
AB  - Rare earth elements (REE) are known to be powerful environmental tracers in
      natural biogeochemical compartments. In this study, the atmospheric deposition of
      REE was investigated using various lichens and mosses as well as herbarium
      samples from 1870 to 1998 from six major forested areas in France. The comparison
      between the REE distribution patterns in organisms and bedrocks showed a regional
      uniformity influence from dust particles originating from the bedrock and/or soil
      weathering that were entrapped by lichens and mosses. These lithological
      signatures were consistent over the last century. The REE patterns of different
      organism species allowed minor influence of the species to be highlighted
      compared to the regional lithology. This was even true where the morphological
      features played a role in the bioaccumulation levels, which were related to the
      variable efficiency in trapping atmospheric dust particles. A comparison between
      REE profiles in the organisms and bark indicated a lack of influence of the
      substrate on lichen REE content. Lichens and mosses appear to be robust passive
      monitors of REE atmospheric deposition over decades because the mineral data was
      preserved in herbarium samples despite organic degradation being shown by carbon
      isotopes and SEM observations. To overcome the bias of REE concentration that
      resulted from organic degradation, the use of a normalized method is recommended
      to interpret the historical samples. 

PMID- 24751591
TI  - Parameters affecting greywater quality and its safety for reuse.
AB  - Reusing greywater (GW) for on-site irrigation is becoming a common practice
      worldwide. Alongside its benefits, GW reuse might pose health and environmental
      risks. The current study assesses the risks associated with on-site GW reuse and
      the main factors affecting them. GW from 34 households in Israel was analyzed for
      physicochemical parameters, Escherichia coli (as an indicator for rotavirus),
      Pseudomonas aeruginosa and Staphylococcus aureus. Each participating household
      filled out a questionnaire about their GW sources, treatment and usages.
      Quantitative microbial risk assessment (QMRA) was performed based on the measured
      microbial quality, and on exposure scenarios derived from the questionnaires and
      literature data. The type of treatment was found to have a significant effect on
      the quality of the treated GW. The average E. coli counts in GW (which exclude
      kitchen effluent) treated by professionally-designed system resulted in
      acceptable risk under all exposure scenarios while the risk from inadequately
      treated GW was above the accepted level as set by the WHO. In conclusion, safe GW
      reuse requires a suitable and well-designed treatment system. A risk-assessment
      approach should be used to adjust the current regulations/guidelines and to
      assess the performance of GW treatment and reuse systems.

PMID- 24751592
TI  - Effects of biochar and other amendments on the physical properties and greenhouse
      gas emissions of an artificially degraded soil.
AB  - Short and long-term impacts of biochar on soil properties under field conditions
      are poorly understood. In addition, there is a lack of field reports of the
      impacts of biochar on soil physical properties, gaseous emissions and C
      stability, particularly in comparison with other amendments. Thus, three
      amendments - biochar produced from oak at 650 degrees C, humic acid (HA) and
      water treatment residual - (WTR) were added to a scalped silty-loam soil @ 0.5%
      (w/w) in triplicated plots under soybean. Over the 4-month active growing season,
      all amendments significantly increased soil pH, but the effect of biochar was the
      greatest. Biochar significantly increased soil-C by 7%, increased sub-nanopore
      surface area by 15% and reduced soil bulk density by 13% compared to control.
      However, only WTR amendment significantly increased soil nanopore surface area by
      23% relative to the control. While total cumulative CH4 and CO2 emissions were
      not significantly affected by any amendment, cumulative N2O emission was
      significantly decreased in the biochar-amended soil (by 92%) compared to control
      over the growing period. Considering both the total gas emissions and the C
      removed from the atmosphere as crop growth and C added to the soil, WTR and HA
      resulted in net soil C losses and biochar as a soil C gain. However, all
      amendments reduced the global warming potential (GWP) of the soil and biochar
      addition even produced a net negative GWP effect. The short observation period,
      low application rate and high intra-treatment variation resulted in fewer
      significant effects of the amendments on the physicochemical properties of the
      soils than one might expect indicating further possible experimentation altering
      these variables. However, there was clear evidence of amendment-soil interaction
      processes affecting both soil properties and gaseous emissions, particularly for
      biochar, that might lead to greater changes with additional field emplacement
      time.

PMID- 24751593
TI  - High performance of a risk calculator that includes renal function in predicting
      mortality of hypertensive patients in clinical application.
AB  - OBJECTIVE: The aim of this study was to assess the accuracy of a risk calculator
      that includes renal function as compared with that of the traditional Framingham
      Risk Score (FRS) in predicting the risk of mortality of hypertensive individuals
      managed in primary care. METHODS: From the databases of British and Italian
      General Practitioners, we retrieved demographic and clinical data for 35 101 UK
      and 27 818 Italian individuals aged 35-74 years with a diagnosis of hypertension.
      Then, the 5-year incidence of cardiovascular events as well as all-cause and
      cardiovascular mortality were recorded for both samples. A comparison analysis of
      the performance of the Individual Data Analysis of Antihypertensive Intervention
      Trials (INDANA) calculator with that of FRS in predicting 5-year all-cause and
      cardiovascular mortality risk was made. RESULTS: The INDANA calculator was more
      accurate than the FRS in predicting all-cause [Deltac 0.038, 95% confidence
      interval (CI) 0.026-0.051 for United Kingdom, and 0.018, 95% CI 0.010-0.027 for
      Italy, both P < 0.0001] and cardiovascular mortality (Deltac 0.050, 95% CI 0.027
      0.074 for United Kingdom, and 0.080, 95% CI 0.059-0.101 for Italy, both P <
      0.0001). By using the INDANA calculator, 20% of the UK and 10% of the Italian
      patients were reclassified to higher risk classes for all-cause mortality, and 25
      and 28%, respectively were reclassified when cardiovascular mortality was
      assessed (P < 0.0001 for all). CONCLUSION: The INDANA calculator proved to be
      more accurate than the FRS in predicting the risk of mortality in hypertensive
      patients and should be considered for systematic adoption for risk stratification
      of hypertensive individuals managed in primary care.

PMID- 24751594
TI  - R wave in aVL lead: an outstanding ECG index in hypertension.
AB  - OBJECTIVES: The voltage of R wave in lead aVL (RaVL) seems to be more tightly
      correlated with left ventricular mass and cardiovascular events than any other
      ECG criterium of left ventricular hypertrophy. We hypothesized that RaVL could be
      an independent predictor of all-cause and cardiovascular death in hypertensive
      individuals. METHODS: The baseline clinical and biological variables as well as
      ECG recordings were analyzed in a prospective cohort of 589 hypertensive
      individuals. RESULTS: After 10 years of follow-up, we observed 95 deaths of which
      53 had a cardiovascular cause. The optimal RaVL voltages to predict all-cause and
      cardiovascular mortality were 0.8 and 0.6  mV, respectively. In a multivariate
      adjusted Cox model, having an RaVL voltage superior to these cutoffs was
      associated with increased risks of all-cause death [hazard ratio: 2.04, 95%
      confidence interval (CI): (1.30-3.22)] and of cardiovascular death [hazard ratio:
      2.89, 95% CI: (1.47-5.68)]. In the whole cohort and with the same adjusted Cox
      regression model, each 0.1  mV increment would increase the risk of all-cause
      death by 1.07 times [95% CI: (1.02-1.12)] and that of cardiovascular death by
      1.13 times [95% CI: (1.06-1.20)]. After excluding in turn patients with positive
      Sokolow index, Cornell voltage, or Cornell product, the results remained
      statistically significant, meaning that RaVL was still able to pick-up high-risk
      patients when other classical and more sophisticated indices were not observable.
      CONCLUSION: The present results strengthen previous reports that demonstrated a
      strong role of RaVL voltage in risk stratification in hypertension.

PMID- 24751595
TI  - Anticontractile activity of perivascular fat in obese mice and the effect of long
      term treatment with melatonin.
AB  - AIMS: It has been demonstrated previously that inflammation in perivascular
      adipose tissue (PVAT) may be implicated in vascular dysfunction. The aim of this
      study was to investigate the functional responses of small mesenteric arteries in
      a hyperphagic animal model of obesity after chronic treatment with melatonin, an
      endogenous hormone with antioxidant and vasculoprotective properties. METHODS AND
      RESULTS: Ten obese mice (ob/ob) and 10 control lean mice (CLM) were treated with
      melatonin 100  mg/kg per day in the drinking water for 8 weeks. Mesenteric small
      resistance arteries were dissected and mounted on a wire myograph and a
      concentration-response to norepinephrine was evaluated in vessels with intact
      PVAT and after PVAT was removed and in the presence of iberiotoxin, a selective
      blocker of BKCA channels as well as under conditions of induced hypoxia in vitro.
      The presence of PVAT reduced the contractile response to norepinephrine in both
      ob/ob and CLM; however, the effect was significantly reduced in ob/ob. The
      anticontractile effect of PVAT completely disappeared with iberiotoxin
      preincubation. After melatonin treatment, inflammation was significantly
      ameliorated, and the contractile response in ob/ob and CLM was significantly
      reduced when PVAT was removed. Anticontractile effect of PVAT that is lost in
      obesity can be rescued using melatonin. A reduced expression of adiponectin and
      adiponectin receptor was observed in perivascular fat of ob/ob, whereas
      significant increase was observed in ob/ob treated with melatonin. CONCLUSION:
      Melatonin seems to exert a protective effect on arteries from both ob/ob and CLM,
      counteracting the adverse effect of hypoxia and iberiotoxin.

PMID- 24751596
TI  - Quantifying quality in DNA self-assembly.
AB  - Molecular self-assembly with DNA is an attractive route for building nanoscale
      devices. The development of sophisticated and precise objects with this technique
      requires detailed experimental feedback on the structure and composition of
      assembled objects. Here we report a sensitive assay for the quality of assembly.
      The method relies on measuring the content of unpaired DNA bases in self
      assembled DNA objects using a fluorescent de-Bruijn probe for three-base
      'codons', which enables a comparison with the designed content of unpaired DNA.
      We use the assay to measure the quality of assembly of several multilayer DNA
      origami objects and illustrate the use of the assay for the rational refinement
      of assembly protocols. Our data suggests that large and complex objects like
      multilayer DNA origami can be made with high strand integration quality up to
      99%. Beyond DNA nanotechnology, we speculate that the ability to discriminate
      unpaired from paired nucleic acids in the same macromolecule may also be useful
      for analysing cellular nucleic acids. 

PMID- 24751597
TI  - Generalized pustulosis associated with disseminated Mycobacterium avium infection
      in a non-AIDS patient.

PMID- 24751598
TI  - Selenium partially prevents cisplatin-induced neurotoxicity: a preliminary study.
AB  - Cisplatin is an anticancer drug and it has neurotoxic effects. On the other hand,
      the neuroprotective effect of selenium was observed in previous studies. However,
      the effect of selenium on cisplatin-induced neurotoxicity has not been studied
      yet. Therefore, we aimed to investigate whether selenium prevent cisplatin
      induced neurotoxicity. Twenty-one male Wistar albino rats were divided into three
      groups: control (C), cisplatin (CS), cisplatin and selenium (CSE, n=7 in each
      group). Cisplatin (12 mg/kg/day, i.p.) was administered for 3 days to CS and CSE
      groups. Also, CSE group received via oral gavage 3 mg/kg/day (twice-a-day as 1.5
      mg/kg) selenium 5 days before of cisplatin injection and continued for 11
      consecutive days. The same volumes of saline were intraperitoneally and orally
      administered to C group at same time. At the end of experimental protocol,
      electrophysiological and histopathological examinations were performed. The nerve
      conduction velocity, amplitude of compound action potential and number of axon of
      CS group were significantly lower than the C group. However, the same parameters
      of CSE group were significantly higher than the CS group. Although, cisplatin has
      a peripheral neurotoxic effect in rats, this effect was partially prevented by
      selenium treatment. Thus, it appears that co-administration of selenium and
      cisplatin may be a useful approach to decrease severity of peripheral
      neurotoxicity.

PMID- 24751599
TI  - Undersampled critical branching processes on small-world and random networks fail
      to reproduce the statistics of spike avalanches.
AB  - The power-law size distributions obtained experimentally for neuronal avalanches
      are an important evidence of criticality in the brain. This evidence is supported
      by the fact that a critical branching process exhibits the same exponent
      [Formula: see text]. Models at criticality have been employed to mimic avalanche
      propagation and explain the statistics observed experimentally. However, a
      crucial aspect of neuronal recordings has been almost completely neglected in the
      models: undersampling. While in a typical multielectrode array hundreds of
      neurons are recorded, in the same area of neuronal tissue tens of thousands of
      neurons can be found. Here we investigate the consequences of undersampling in
      models with three different topologies (two-dimensional, small-world and random
      network) and three different dynamical regimes (subcritical, critical and
      supercritical). We found that undersampling modifies avalanche size
      distributions, extinguishing the power laws observed in critical systems.
      Distributions from subcritical systems are also modified, but the shape of the
      undersampled distributions is more similar to that of a fully sampled system.
      Undersampled supercritical systems can recover the general characteristics of the
      fully sampled version, provided that enough neurons are measured. Undersampling
      in two-dimensional and small-world networks leads to similar effects, while the
      random network is insensitive to sampling density due to the lack of a well
      defined neighborhood. We conjecture that neuronal avalanches recorded from local
      field potentials avoid undersampling effects due to the nature of this signal,
      but the same does not hold for spike avalanches. We conclude that undersampled
      branching-process-like models in these topologies fail to reproduce the
      statistics of spike avalanches. 

PMID- 24751600
TI  - Birth in a health facility--inequalities among the Ethiopian women: results from
      repeated national surveys.
AB  - BACKGROUND: Uptake of health facilities for delivery care in Ethiopia has not
      been examined in the light of equality. We investigated differences in
      institutional deliveries by urbanity, administrative region, economic status and
      maternal education. METHODS: This study was based on nation-wide repeated surveys
      undertaken in the years 2000, 2005, and 2011. The surveys used a cluster sampling
      design. Women of reproductive age were interviewed on the place of their last
      delivery. Data was analyzed using logistic regressions to estimate the weighted
      association between birth in a health facility and study's predictors. RESULTS:
      Utilization of health institutions for deliveries has improved throughout the
      study period, however, rates remain low (5.4%,2000 and 11.8%,2011). Compared with
      women from rural places, women from urban areas had independent OR of a health
      facility delivery of 4.9 (95% CI: 3.4, 7.0), 5.0 (95% CI: 3.6, 6.9), and 4.6 (95%
      CI: 3.5, 6.0) in 2000, 2005, and 2011, respectively. Women with secondary/higher
      education had more deliveries in a healthcare facility than women with no
      education, and these gaps widened over the years (OR: 35.1, 45.0 and 53.6 in
      2000, 2005, and 2011, respectively). Women of the upper economic quintile had 3.0
      7.2 times the odds of healthcare facility deliveries, compared with the lowest
      quintile, with no clear trend over the years. While Addis-Ababa and Dire Dawa
      remained with the highest OR for deliveries in a health facility compared with
      Amhara, other regions displayed shifts in their relative ranking with Oromiya,
      SNNPR, Afar, Harari, and Somali getting relatively worse over time. CONCLUSIONS:
      The disparity related to urbanity or education in the use of health facility for
      birth in Ethiopia is staggering. There is a small inequality between most regions
      except Addis Ababa/Dire Dawa and sign of abating inequity between economic strata
      except for the richest households.

PMID- 24751601
TI  - Ultrafast atomic layer-by-layer oxygen vacancy-exchange diffusion in double
      perovskite LnBaCo2O5.5+delta thin films.
AB  - Surface exchange and oxygen vacancy diffusion dynamics were studied in double
      perovskites LnBaCo2O5.5+delta (LnBCO) single-crystalline thin films (Ln = Er, Pr;
      -0.5 < delta < 0.5) by carefully monitoring the resistance changes under a
      switching flow of oxidizing gas (O2) and reducing gas (H2) in the temperature
      range of 250 ~ 800  degrees C. A giant resistance change DeltaR by three to four
      orders of magnitude in less than 0.1 s was found with a fast oscillation behavior
      in the resistance change rates in the DeltaR vs. t plots, suggesting that the
      oxygen vacancy exchange diffusion with oxygen/hydrogen atoms in the LnBCO thin
      films is taking the layer by layer oxygen-vacancy-exchange mechanism. The first
      principles density functional theory calculations indicate that hydrogen atoms
      are present in LnBCO as bound to oxygen forming O-H bonds. This unprecedented
      oscillation phenomenon provides the first direct experimental evidence of the
      layer by layer oxygen vacancy exchange diffusion mechanism.

PMID- 24751602
TI  - Kinematics of visually-guided eye movements.
AB  - One of the hallmarks of an eye movement that follows Listing's law is the half
      angle rule that says that the angular velocity of the eye tilts by half the angle
      of eccentricity of the line of sight relative to primary eye position. Since all
      visually-guided eye movements in the regime of far viewing follow Listing's law
      (with the head still and upright), the question about its origin is of
      considerable importance. Here, we provide theoretical and experimental evidence
      that Listing's law results from a unique motor strategy that allows minimizing
      ocular torsion while smoothly tracking objects of interest along any path in
      visual space. The strategy consists in compounding conventional ocular rotations
      in meridian planes, that is in horizontal, vertical and oblique directions (which
      are all torsion-free) with small linear displacements of the eye in the frontal
      plane. Such compound rotation-displacements of the eye can explain the kinematic
      paradox that the fixation point may rotate in one plane while the eye rotates in
      other planes. Its unique signature is the half-angle law in the position domain,
      which means that the rotation plane of the eye tilts by half-the angle of gaze
      eccentricity. We show that this law does not readily generalize to the velocity
      domain of visually-guided eye movements because the angular eye velocity is the
      sum of two terms, one associated with rotations in meridian planes and one
      associated with displacements of the eye in the frontal plane. While the first
      term does not depend on eye position the second term does depend on eye position.
      We show that compounded rotation - displacements perfectly predict the average
      smooth kinematics of the eye during steady- state pursuit in both the position
      and velocity domain. 

PMID- 24751604
TI  - Editorial 50.2.

PMID- 24751603
TI  - R-ESHAP plus pegfilgrastim as an effective peripheral stem cell mobilization
      regimen for autologous stem-cell transplantation in patients with
      relapsed/refractory diffuse large B-cell lymphoma.
AB  - Stem cell (SC) mobilization is significantly influenced by the mobilization
      schedule in patients with lymphoma. We evaluated data from 30 patients with
      relapsed or refractory diffuse large B-cell lymphoma (DLBCL) undergoing SC
      mobilization. All received R-ESHAP plus a single dose of pegfilgrastim. All
      patients collected ? 2 * 10(6) CD34+cells/kg, 80% of them at least 5 * 10(6)
      CD34+cells/kg. Adverse effects of the regimen included myelosuppression and
      neutropenic fever. Herein, our results suggest that R-ESHAP plus pegfilgrastim is
      a highly effective mobilization strategy in patients affected by DLBCL associated
      with a low incidence of adverse events.

PMID- 24751605
TI  - Semi-extended nailing of metaphyseal tibia fractures: alignment and incidence of
      postoperative knee pain.
AB  - OBJECTIVES: To review a large series of tibial metaphyseal fractures treated with
      nailing in semi-extension (20-30 degrees) using a superomedial portal. To report
      on the quality and maintenance of reduction. To compare knee pain at final follow
      up with a group nailed in hyperflexion (>90 degrees) with a standard inferior
      incision and parapatellar approach. DESIGN: Retrospective cohort study. SETTING:
      Academic medical center. PATIENTS: One hundred eighty-five consecutive tibia
      fractures were treated with intramedullary nails. Eighty-four patients with
      fractures affecting the proximal (50) or distal (34) metaphysis were nailed with
      the knee in semi-extension. One hundred one with diaphyseal fractures were nailed
      in standard hyperflexion and were used as a comparison group. OUTCOME MEASURES:
      Knee pain was recorded at the final follow-up and graded on a 0-3 scale as per
      Court-Brown. Alignment was measured on full-length biplanar radiographs
      immediately postoperative and compared with the same radiographs at union.
      RESULTS: There was no statistical difference in the number of patients without
      knee pain at union (P = 0.7). Radiographic angulation at the fracture was <5
      degrees in all patients immediately postoperative, and no patient lost reduction.
      The average follow-up was 2.3 years. CONCLUSIONS: Knee pain after semi-extended
      tibial nailing was similar in frequency compared with standard nailing. There
      were no significant angulatory deformities, and no losses of reduction for both
      proximal and distal metaphyseal fractures nailed with the semi-extended
      technique. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors
      for a complete description of levels of evidence.

PMID- 24751606
TI  - Malpositioning of the lag screws by 1- or 2-screw nailing systems for
      pertrochanteric femoral fractures: a biomechanical comparison of gamma 3 and
      intertan.
AB  - OBJECTIVES: The aim of this investigation was to perform a biomechanical
      comparison between 1- and 2-screw systems used for the treatment of
      intertrochanteric fractures for centralized and decentralized placement of
      femoral neck screws of failure loads, stiffness, survival rates, tip apex
      distance (TAD), and failure mode. METHODS: As fracture model, an AO 31A2.3
      fracture was used. Twelve pairs of human cadaver femora were tested. Femoral neck
      screws were implanted in the femoral head in center/center, posterior/central,
      and anterior/superior position in axial/frontal plane. A single-screw system
      (Gamma 3 Locking Nail; Stryker GmbH & Co. KG) and a 2-screw system (Trigen
      Intertan; Smith & Nephew GmbH) were used. To simulate the load in situ, a cyclic
      load was carried for 10,000 cycles in a material testing machine. If no cyclic
      failure occurred, femora were loaded until the failure. The systems were compared
      according to the stiffness, survivability through 10 k cycles, TAD, and load to
      failure. RESULTS: None of the tested bones failed at center/center location in
      the decentralized positions 3 Gamma Nail and 2 Intertan specimens failed during
      cyclic testing. The 2-screw system resisted higher forces in all positions
      (Gamma: 5370N +/- 1924, Intertan: 7650N +/- 2043; P = 0.014). CONCLUSIONS: Based
      on these data, it is clear that both the nail systems showed a higher
      biomechanical stability with a lower TAD. The 2 specimens that failed with the
      Intertan in the cyclic tests had a TAD >=49 mm. The cutout failures that we
      detected during cyclic testing in the Gamma system had a TAD >=30 mm. Thus, it is
      clear that the TAD affects failure independent of the implant used. With a less
      than ideal lag screw placement, however, the Intertan system with 2 integrated
      screws was able to withstand higher loads in this study.

PMID- 24751607
TI  - Short-term follow-up of pertrochanteric fractures treated using the proximal
      femoral locking plate.
AB  - OBJECTIVES: The proximal femoral locking compression plate is a fixed angled
      anatomically contoured stainless steel plate used to treat pertrochanteric
      fractures of the proximal femur. Recent reports quote a high failure rate
      associated with this implant. We aimed to identify the common methods of failure
      and determine the elements of surgical techniques that could be altered to
      potentially improve outcomes should this implant be used for the treatment of
      unstable pertrochanteric fractures. DESIGN: Retrospective chart analysis.
      SETTING: Three separate centers. PATIENTS: Twenty-nine patients with 29
      fractures. INTERVENTION: All patients were treated for pertrochanteric fractures
      using the proximal femoral locking compression plate. OUTCOME MEASURES: The
      patient demographics, fracture classification, implant details, and
      complications. RESULTS: Twelve of 29 fractures (41.4%) suffered a complication
      associated with the implant, and 83% of these occurred in elderly women.
      Complications included bending, backing-out, fracture, or cut-out of the proximal
      screws and plate fracture. Common technical errors included the following: (1)
      leaving the plate proud proximally, (2) malposition of the proximal screws within
      the femoral neck/head, (3) inappropriate use of the hook plate, (4) creating too
      ridged a construct when used as a bridging plate. CONCLUSIONS: Our experience
      with the use of this implant suggests an unacceptably high failure rate (41.4%).
      A knowledge of the common pitfalls encountered when using this device is critical
      in an effort to reduce failure rates. Based on our data, we would urge caution
      when considering this device for unstable pertrochanteric fractures, especially
      in the elderly female. LEVEL OF EVIDENCE: Prognostic Level IV. See Instructions
      for Authors for a complete description of levels of evidence.

PMID- 24751608
TI  - Surgical management of coracoid fractures: technical tricks and clinical
      experience.
AB  - The coracoid process plays a pivotal role in the foundation of the coracoacromial
      arch and in cases of displaced fractures; surgical management may be warranted to
      avoid functional compromise or impingement. A direct approach through Langer's
      lines allows for easy exposure and direct visualization for an anatomic reduction
      of simple fractures through the shaft or base of the coracoid. An anterior
      approach for fractures that extend into the superior glenoid fossa allows for
      direct exposure to obtain an anatomic articular reduction and indirect reduction
      of the coracoid fracture. In cases where a complex glenoid or scapula neck/body
      fracture is being addressed simultaneously either a posterior Judet approach can
      be used with an indirect reduction method or a separate anterior approach must be
      combined to address it if not in continuity with the superior scapular segment.
      Implant selection, primarily interfragmentary screws or a buttress plate, should
      be based on the size of the fragment, the degree of comminution, and the degree
      of articular involvement to ensure adequate stabilization. The purpose of this
      manuscript was to describe a stepwise approach to the surgical management of
      displaced coracoid fractures, describe surgical tips and techniques, and to
      present the clinical outcomes in 22 patients after surgical treatment with this
      approach.

PMID- 24751609
TI  - Short versus long intramedullary nails for treatment of intertrochanteric femur
      fractures (OTA 31-A1 and A2).
AB  - OBJECTIVES: The purpose of this study was to compare blood loss and operative
      times associated with long versus short intramedullary nails for
      intertrochanteric fracture fixation and rate of periprosthetic fracture. DESIGN:
      A retrospective study. SETTING: Level 1 trauma center. PATIENTS: One hundred
      ninety-four patients with an intertrochanteric fracture (AO/OTA class 31-A1 and
      A2) and low-energy mechanism of injury treated by 1 of 4 fellowship-trained
      orthopaedic traumatologists. INTERVENTION: Short versus long intramedullary nail.
      METHODS: Medical records were reviewed for age, gender, estimated blood loss
      (EBL), transfusion rate, operative time, length of stay, and incidence of
      periprosthetic fracture. Variables were statistically compared between long and
      short intramedullary nails, with statistical significance at P < 0.05. RESULTS:
      The average EBL (135.5 +/- 91.9 mL) and transfusion rate (57.1%) for long nails
      were found to be significantly greater (P = 0.002) than the EBL (92.6 +/- 47.2
      mL) and transfusion rate (40.2%) for short nails. Average operative time was also
      found to be significantly greater (P < 0.001) for long (56.8 +/- 19.4 minutes)
      than for short (44.0 +/- 10.7 minutes) intramedullary nail procedures. The
      overall incidence of periprosthetic fracture was 0.5%, one patient with initial
      treatment of a long intramedullary nail. CONCLUSIONS: Statistically significant
      lower operative time, EBL, and transfusion rate were found in this study for
      short intramedullary nails. There were no differences seen in length of stay or
      periprosthetic fracture. The incidence of periprosthetic fracture was very low in
      both cohorts. Further study with greater statistical power is needed. LEVEL OF
      EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete
      description of levels of evidence.

PMID- 24751610
TI  - Rats eat a cafeteria-style diet to excess but eat smaller amounts and less
      frequently when tested with chow.
AB  - BACKGROUND: Obesity is associated with excessive consumption of palatable, energy
      dense foods. The present study used an animal model to examine feeding patterns
      during exposure to and withdrawal from these foods. METHODS: Male Sprague Dawley
      rats were exposed to standard lab chow only (Chow rats) or a range of cafeteria
      style foods eaten by people (Caf rats). After 1, 4, 7 and 10 weeks of diet in
      their home cage, rats were subjected to 24-hour test sessions in a Comprehensive
      Lab Animal Monitoring System (CLAMS). In the first two test sessions, Chow rats
      were exposed to standard lab chow only while Caf rats were exposed to a biscuit
      and high-fat chow diet. In the final two test sessions, half the rats in each
      group were switched to the opposing diet. In each session we recorded numbers of
      bouts, energy consumed per bout, and intervals between bouts across the entire 24
      hours. RESULTS: Relative to Chow rats, Caf rats initiated fewer bouts but
      consumed more energy per bout; however, their motivation to feed in the CLAMS
      declined over time, which was attributed to reduced variety of foods relative to
      their home cage diet. This decline in motivation was especially pronounced among
      Caf rats switched from the palatable CLAMS diet to standard lab chow only: the
      reduced energy intake in this group was due to a modest decline in bout frequency
      and a dramatic decline in bout size. CONCLUSIONS: Exposure to a cafeteria-diet,
      rich in variety, altered feeding patterns, reduced rats' motivation to consume
      palatable foods in the absence of variety, and further diminished motivation to
      feed when palatable foods were withdrawn and replaced with chow. Hence, variety
      is a key factor in driving excessive consumption of energy dense foods, and
      therefore, excessive weight gain.

PMID- 24751611
TI  - Chloroquine synergizes sunitinib cytotoxicity via modulating autophagic,
      apoptotic and angiogenic machineries.
AB  - Tyrosine kinases play a pivotal role in oncogenesis. Although tyrosine kinase
      inhibitors as sunitinib malate are used in cancer therapy, emerging studies
      report compromised cytotoxicity when used as monotherapy and thus combinations
      with other anti-cancer agents is recommended. Chloroquine is a clinically
      available anti-malarial agent which has been shown to exhibit anti-cancer
      activity. In the current study, we questioned whether chloroquine can modulate
      sunitinib cytotoxicity. We found that chloroquine synergistically augmented
      sunitinib cytotoxicity on human breast (MCF-7 and T-47D), cervical (Hela),
      colorectal (Caco-2 and HCT116), hepatocellular (HepG2), laryngeal (HEp-2) and
      prostate (PC3) cancer cell lines as indicated by combination and concentration
      reduction indices. These results were also consistent with that of Ehrlich
      ascites carcinoma (EAC) Swiss albino mice models as confirmed by tumor volume,
      weight, histopathological examination and PCNA expression. Sunitinib induced
      autophagy via upregulating beclin-1 expression which was blocked by chloroquine
      as evidenced by accumulated SQTSM1/p62 level. Furthermore, chloroquine augmented
      sunitinib-induced apoptosis by decreasing survivin level and increasing caspase 3
      activity. Chloroquine also enhanced the antiangiogenic capacity of sunitinib as
      indicated by decreased CD34 expression and peritoneal/skin angiogenesis.
      Sunitinib when combined with chloroquine also increased reactive nitrogen species
      production via increasing inducible nitric oxide synthase expression and nitric
      oxide level whilst reduced reactive oxygen species production by increasing GSH
      level, activities of glutathione peroxidase and catalase and reducing lipid
      peroxides compared to sunitinib-only treated group. Taken together, these
      findings suggest that chloroquine enhanced sunitinib cytotoxicity in a
      synergistic manner via inducing apoptosis while switching off autophagic and
      angiogenic machineries. Nevertheless, further studies are required to elucidate
      the efficacy and safety profile of such combination. 

PMID- 24751612
TI  - Right aortic arch and ductus arteriosus: a case diagnosed during the first
      trimester of pregnancy.

PMID- 24751613
TI  - Response to the letter to the editor.

PMID- 24751614
TI  - From cytokine to myokine: the emerging role of interleukin-6 in metabolic
      regulation.
AB  - The lack of physical activity and overnutrition in our modern lifestyle
      culminates in what we now experience as the current obesity and diabetes
      pandemic. Medical research performed over the past 20 years identified chronic
      low-grade inflammation as a mediator of these metabolic disorders. Hence, finding
      therapeutic strategies against this underlying inflammation and identifying
      molecules implicated in this process is of significant importance. Following the
      observation of an increased plasma concentration of interleukin-6 (IL-6) in obese
      patients, this protein, known predominantly as a pro-inflammatory cytokine, came
      into focus. In an attempt to clarify its importance, several studies implicated
      IL-6 as a co-inducer of the development of obesity-associated insulin resistance,
      which precedes the development of type 2 diabetes. However, the identification of
      IL-6 as a myokine, a protein produced and secreted by skeletal muscle to fulfil
      paracrine or endocrine roles in the insulin-sensitizing effects following
      exercise, provides a contrasting and hence paradoxical identity of this protein
      in the context of metabolism. We review here the literature considering the
      complex, pleiotropic role of IL-6 in the context of metabolism in health and
      disease. 

PMID- 24751615
TI  - Malignant cylindroma arising as a solitary neck lesion.

PMID- 24751616
TI  - Pure trisomy 2p syndrome in two siblings with an unbalanced translocation and
      minimal terminal 12q monosomy characterized by high-density microarray.
AB  - Pure partial trisomy 2p patients have rarely been reported. Oligonucleotide array
      analysis has proved to be important for examining 2p rearrangements to delineate
      the involved segment and to rule out additional imbalances modifying the
      phenotype. Here, we report 2 siblings with an unbalanced translocation that led
      to a partial trisomy 2p (p22.3pter) and a terminal deletion of 12q (q24.33qter).
      This finding was characterized by the molecular karyotyping of both siblings. The
      12q loss spanned approximately 300 kb and did not yield clinical features in our
      patients. The trisomic region in the short arm of chromosome 2 spanned 32.8 Mb
      and yielded phenotypic features of pure distal 2p trisomy, notably facial
      anomalies, growth failure, and psychomotor delay. The clinical features of our
      patients help to delineate the phenotype of the pure trisomy 2p syndrome. Patient
      2 also showed a horseshoe kidney which is a previously unrecognized defect
      associated with this syndrome.

PMID- 24751617
TI  - Historical perspective.

PMID- 24751618
TI  - Defining the nutritional needs of preterm infants.
AB  - Nutritional needs are defined as the amount and chemical form of a nutrient
      needed to support normal health, growth and development without disturbing the
      metabolism of other nutrients. Nutrient intake recommendations are based on the
      estimated average requirement (EAR) of a population group. Enteral and parenteral
      needs differ for many nutrients because of differences in bioavailability and
      utilization. Assuming a near-normal distribution of nutrient needs, the reference
      nutrient intake (RNI--also called population reference intake or recommended
      dietary allowance) is equal to the EAR plus two standard deviations of the
      distribution, with the exception of energy intake where the reference intake is
      equal to the EAR. The upper level (UL) is the highest level of intake where no
      untoward effects can be detected in virtually all individuals in a specific
      population group. The acceptable range of intakes (AR) is the range from the EAR
      to the UL that is considered safe, however preterm infants are not a homogeneous
      population thus intake often needs to be individualized based on clinical
      condition and developmental stage.

PMID- 24751620
TI  - Assessing the evidence from neonatal nutrition research.
AB  - Being up to date with current medical research in order to deliver the best
      possible care to patients has never been easy, and it is not easy today. Still,
      clinical decision-making at all levels of medical care needs to be made based on
      evidence. This chapter aims to provide tools for understanding how to assess the
      medical literature. It starts with an overview of study designs. Each of the
      study designs can provide useful information if applied in the appropriate
      situation, with the proper methods, and if properly reported. The strengths and
      limitations of each study design, mainly in relation to the potential to
      establish causality, are presented. Then, the chapter provides a summary of the
      key elements of practicing evidence-based medicine, the necessity of today's
      medicine. These key elements are as follows: formulation of an answerable
      question (the problem); finding the best evidence; critical appraisal of the
      evidence, and applying the evidence to the treatment of patients. Special focus
      is placed on critical appraisal of the evidence, as not all research is of good
      quality. Studies are frequently biased and their results are incorrect. In turn,
      this can lead one to draw false conclusions. While an attempt was made to discuss
      all of the issues in the context of studies conducted in neonatal nutrition, the
      principles are applicable to practicing medicine in general.

PMID- 24751619
TI  - Nutrition, growth and clinical outcomes.
AB  - Recommendations about the nutritional management of preterm infants, especially
      of extremely low gestational age (or extremely low birth weight) neonates, have
      been published by a number of pediatric and nutritional organizations. The
      objectives of these recommendations are to provide nutrients to approximate the
      rate of growth and composition of weight gain for a normal fetus of the same
      postmenstrual age, to maintain normal concentrations of blood and tissue
      nutrients, and to achieve a satisfactory functional development. Achieving these
      goals requires an understanding of the intrauterine growth rate to be targeted
      and of the nutrient requirements of preterm infants. Birth weight-based
      intrauterine curves should be used to monitor postnatal growth of preterm infants
      in neonatal intensive care units. Although primarily provided by observational
      studies or historic control studies, data demonstrate that growth and
      neurodevelopmental outcomes correlate with nutritional intake. The implementation
      of standardized feeding guidelines reduces nutritional practice variation and
      facilitates postnatal growth and improved clinical outcomes.

PMID- 24751621
TI  - Amino acids and proteins.
AB  - Amino acids and protein are key factors for growth. The neonatal period requires
      the highest intake in life to meet the demands. Those demands include amino acids
      for growth, but proteins and amino acids also function as signalling molecules
      and function as neurotransmitters. Often the nutritional requirements are not
      met, resulting in a postnatal growth restriction. However, current knowledge on
      adequate levels of both amino acid as well as protein intake can avoid under
      nutrition in the direct postnatal phase, avoid the need for subsequent catch-up
      growth and improve later outcome.

PMID- 24751622
TI  - Energy requirements, protein-energy metabolism and balance, and carbohydrates in
      preterm infants.
AB  - Energy is necessary for all vital functions of the body at molecular, cellular,
      organ, and systemic levels. Preterm infants have minimum energy requirements for
      basal metabolism and growth, but also have requirements for unique physiology and
      metabolism that influence energy expenditure. These include body size, postnatal
      age, physical activity, dietary intake, environmental temperatures, energy losses
      in the stool and urine, and clinical conditions and diseases, as well as changes
      in body composition. Both energy and protein are necessary to produce normal
      rates of growth. Carbohydrates (primarily glucose) are principle sources of
      energy for the brain and heart until lipid oxidation develops over several days
      to weeks after birth. A higher protein/energy ratio is necessary in most preterm
      infants to approximate normal intrauterine growth rates. Lean tissue is
      predominantly produced during early gestation, which continues through to term.
      During later gestation, fat accretion in adipose tissue adds increasingly large
      caloric requirements to the lean tissue growth. Once protein intake is sufficient
      to promote net lean body accretion, additional energy primarily produces more
      body fat, which increases almost linearly at energy intakes >80-90 kcal/kg/day in
      normal, healthy preterm infants. Rapid gains in adiposity have the potential to
      produce later life obesity, an increasingly recognized risk of excessive energy
      intake. In addition to fundamental requirements for glucose, protein, and fat, a
      variety of non-glucose carbohydrates found in human milk may have important roles
      in promoting growth and development, as well as production of a gut microbiome
      that could protect against necrotizing enterocolitis.

PMID- 24751623
TI  - Enteral and parenteral lipid requirements of preterm infants.
AB  - Lipids provide infants with most of their energy needs. The major portion of the
      fat in human milk is found in the form of triglycerides, the phospholipids and
      cholesterol contributing for only a small proportion of the total fat. Long-chain
      polyunsaturated fatty acids (LC-PUFAs) are crucial for normal development of the
      central nervous system and have potential for long-lasting effects that extend
      beyond the period of dietary insufficiency. Given the limited and highly variable
      formation of docosahexaenoic acid (DHA) from alpha-linolenic acid, and because
      DHA is critical for normal retinal and brain development in the human, DHA should
      be considered to be conditionally essential during early development. In early
      enteral studies, the amount of LC-PUFAs administered in formula was chosen to
      produce the same concentration of arachidonic acid and DHA as in term breast
      milk. Recent studies report outcome data in preterm infants fed formula with DHA
      content 2-3 times higher than the current concentration. Overall, these studies
      show that providing larger amounts of DHA supplements is associated with better
      neurological outcomes and may provide other health benefits. One study further
      suggests that the smallest babies are the most vulnerable to DHA deficiency and
      likely to reap the greatest benefit from high-dose DHA supplementation. Current
      nutritional management may not provide sufficient amounts of preformed DHA during
      the parenteral and enteral nutrition periods and in very preterm/very low birth
      weight infants until due date and higher amounts than those routinely used are
      likely to be necessary to compensate for intestinal malabsorption, DHA oxidation,
      and early deficit. Recommendations for the healthcare provider are made in order
      to prevent lipid and more specifically LC-PUFA deficit. Research should be
      continued to fill the gaps in knowledge and to further refine the adequate intake
      for each group of preterm infants.

PMID- 24751624
TI  - Water, sodium, potassium and chloride.
AB  - The sudden disruption of excessive placental supply with fluids and electrolytes
      is challenging for neonatal physiology during the period of postnatal adaptation.
      Different from many other nutrients, the body experiences large changes in daily
      requirements during the first 7-14 postnatal days, and on the other hand does not
      tolerate conditions of excess and deficiency very well. Imbalances of fluid and
      electrolytes are common in neonates, which--in addition--might be further
      aggravated by NICU treatment procedures. Therefore, fluid and electrolyte
      management can be one of the most challenging aspects of neonatal care of the
      premature infant. An understanding of the physiological adaptation process to
      extrauterine life--and how immaturity effects that transition--is the basis which
      is needed to understand and manage fluid and electrolyte balance in premature
      infants. This chapter addresses the physiology of postnatal adaptation and other
      aspects of fluid and electrolyte management (concerning potassium, sodium and
      chloride) of the preterm infant.

PMID- 24751625
TI  - Nutritional care of premature infants: microminerals.
AB  - Microminerals, including iron, zinc, copper, selenium, manganese, iodine,
      chromium and molybdenum, are essential for a remarkable array of critical
      functions and need to be supplied in adequate amounts to preterm infants. Very
      low birth weight (VLBW) infants carry a very high risk of developing iron
      deficiency which can adversely affect neurodevelopment. However, a too high iron
      supply in iron-replete VLBW infants may induce adverse effects such as increased
      infection risks and impaired growth. Iron needs are influenced by birth weight,
      growth rates, blood losses (phlebotomy) and blood transfusions. An enteral iron
      intake of 2 mg/kg/day for infants with a birth weight of 1,500-2,500 g and 2-3
      mg/kg/day for VLBW infants is recommended. Higher doses up to 6 mg/kg/day are
      needed in infants receiving erythropoietin treatment. Regular monitoring of serum
      ferritin during the hospital stay is advisable. Routine provision of iron with
      parenteral nutrition for VLBW infants is not recommended. Less certainty exists
      for the advisable intakes of other microminerals. It appears prudent to provide
      enterally fed VLBW infants with daily amounts per kilogram body weight of 1.4-2.5
      mg zinc, 100-230 MUg copper, 5-10 MUg selenium, 1-15 MUg manganese, 10-55 MUg
      iodine, 0.03-2.25 MUg chromium, and 0.3-5 MUg molybdenum. Future scientific
      findings may justify deviations from these suggested ranges.

PMID- 24751626
TI  - Calcium, phosphorus, magnesium and vitamin D requirements of the preterm infant.
AB  - Proper mineral and vitamin D nutrition in preterm infants is essential for
      adequate bone health because preterm infants are at a risk of prematurely
      developing osteopenia. This chapter focuses on nutritional aspects of the
      requirements after a brief description of the perinatal physiology of minerals
      and vitamin D. The rationale for estimation of nutritional mineral requirements
      of the preterm infant (based upon estimates of the intrauterine skeletal
      accretion rate of minerals, and upon estimates of the coefficient of intestinal
      absorption) is first described. Previous expert recommendations are reviewed and
      compared to the present recommendations. Finally, vitamin D requirements are
      thoroughly reviewed based upon what is known of the physiology of vitamin D in
      preterm infants. A suggestion that each extremely preterm infant should be
      monitored for adequate vitamin D status is made.

PMID- 24751627
TI  - Vitamins--conventional uses and new insights.
AB  - There are 13 nutrients classified as vitamins: 4 'fat-soluble' and 9 'water
      soluble'. All are essential to maintain healthy homeostasis and metabolic
      function. Preterm infants are born with low levels and reduced stores of fat
      soluble vitamins. Active placental transfer of water-soluble vitamins ensures
      high levels at birth, but as they are not stored, levels fall rapidly. All VLBW
      and ELBW infants require vitamins to be provided soon after birth. Quantifying
      exact requirements of each vitamin which will meet the needs for all infants is
      difficult due to a limited evidence base. However, timely prescription of vitamin
      supplements and awareness of situations where delivery or uptake might be
      compromised will help to ensure that these vulnerable patients do not suffer from
      vitamin deficiencies. Multivitamin preparations are available for parenteral and
      enteral use. Vitamins A, C and E have important functions as antioxidants.
      Further research is required to understand optimal doses and routes of
      administration for initial and ongoing nutritional support.

PMID- 24751628
TI  - The developing intestinal microbiome: probiotics and prebiotics.
AB  - The microbes in the human intestinal tract interact with the host to form a
      'superorganism'. The functional aspects of the host microbe interactions are
      being increasingly scrutinized and it is becoming evident that this interaction
      in early life is critical for development of the immune system and metabolic
      function and aberrations may result in life-long health consequences. Evidence is
      suggesting that such interactions occur even before birth, where the microbes may
      be either beneficial or harmful, and possibly even triggering preterm birth. Mode
      of delivery, use of antibiotics, and other perturbations may have life-long
      consequences in terms of health and disease. Manipulating the microbiota by use
      of pro- and prebiotics may offer a means for maintenance of 'healthy' host
      microbe interactions, but over-exuberance in their use also has the potential to
      cause harm. Considerable controversy exists concerning the routine use of
      probiotics in the prevention of necrotizing enterocolitis. This chapter will
      provide a brief overview of the developing intestinal microbiome and discuss the
      use of pro- and prebiotics in preterm infants.

PMID- 24751629
TI  - Practice of parenteral nutrition in VLBW and ELBW infants.
AB  - Preterm infants have limited nutrient stores at birth, take time to establish
      enteral feeding, are at risk of accumulating significant nutrient deficits, and
      frequently suffer poor growth - all risks which are associated with poorer
      neurodevelopmental outcome. Parenteral nutrition (PN) provides a relatively safe
      means of meeting nutrient intakes, and is widely used in preterm infants in the
      initial period after birth. PN is also important for infants who may not tolerate
      enteral feeds such as those with congenital or acquired gut disorders such as
      necrotizing enterocolitis (NEC). PN is associated with several short-term
      benefits, but clear evidence of long-term benefit from controlled trials in
      neonates is lacking. There are many compositional, practical and risk aspects
      involved in neonatal PN. In most preterm infants, authorities recommend amino
      acid intakes approximating to 3.5-4 g/kg/day of protein, lipid intakes of 3-4
      g/kg/day and sufficient carbohydrate to meet a total energy intake of 90-110
      kcal/kg/day. Where PN is the sole source of nutrition, careful attention to
      micronutrient requirements is necessary. PN may be administered via peripheral
      venous access if the osmolality allows, but in many cases requires central venous
      access. Standardized PN bags may meet the nutrient needs of many preterm infants
      over the first few days, although restricted fluid intakes mean that many receive
      inadequate amounts especially of amino acids. PN can be associated with increased
      rates of bacterial and fungal sepsis, mechanical complications related to venous
      line placement and miscalculations and errors in manufacture, supply and
      administration. PN is also associated with metabolic derangements, hepatic
      dysfunction, and risks contamination with toxins such as aluminum, which enter
      the solutions during manufacturing. PN must only be administered in units with
      good quality control, strict asepsis in manufacture and administration and
      multidisciplinary teams focused on nutrient needs and intakes.

PMID- 24751630
TI  - Preterm nutrition and the brain.
AB  - The brain is the most highly metabolic organ in the preterm neonate and consumes
      the greatest amount of nutrient resources for its function and growth. As preterm
      infants survive at greater rates, neurodevelopment has become the primary
      morbidity outcome of interest. While many factors influence neurodevelopmental
      outcomes in preterm infants, nutrition is of particular importance because the
      healthcare team has a great deal of control over its provision. Studies over the
      past 30 years have emphasized the negative neurodevelopmental consequences of
      poor nutrition and growth in the preterm infant. While all nutrients are
      important for brain development, certain ones including glucose, protein, fats
      (including long-chain polyunsaturated fatty acids), iron, zinc, copper, iodine,
      folate and choline have particularly large roles in the preterm infant. They
      affect major brain processes such as neurogenesis, neuronal differentiation,
      myelination and synaptogenesis, all of which are proceeding at a rapid pace
      between 22 and 42 weeks' post-conception. At the macronutrient level, weight
      gain, linear growth (independent of weight gain) and head circumference growth
      are markers of nutritional status. Each has been associated with long-term
      neurodevelopment. The relationship of micronutrients to neurodevelopment in
      preterm infants is understudied in spite of the large effect these nutrients have
      in other young populations. Nutrients do not function alone to stimulate brain
      development, but rather in concert with growth factors, which in turn are
      dependent on adequate nutrient status (e.g. protein, zinc) as well as on
      physiologic status. Non-nutritional factors such as infection, corticosteroids,
      and inflammation alter how nutrients are accreted and distributed, and also
      suppress growth factor synthesis. Thus, nutritional strategies to optimize brain
      growth and development include assessment of status at birth, aggressive
      provision of nutrients that are critical in this time period, control of non
      nutritional factors that impede brain growth and repletion of nutrient deficits.

PMID- 24751631
TI  - Practice of enteral nutrition in very low birth weight and extremely low birth
      weight infants.
AB  - The perinatal period is critical for human development. The brain of very low
      birth weight (VLBW, <1,500 g) infants is particularly vulnerable to
      undernutrition. Enteral nutrition is of major importance for the growth and the
      development of the gastrointestinal tract, which depends on the amount and
      composition of feeds. Feeding intolerance and the risk of necrotizing
      enterocolitis (NEC) are key concerns with enteral nutrition in VLBW infants.
      Controversies exist on how to feed VLBW infants during the first weeks of life,
      particularly in extremely low birth weight (ELBW, <1,000 g) infants. Unreasonable
      concerns lead to iatrogenic malnutrition, gastrointestinal atrophy, and
      parenteral nutrition-related complications. Many studies in the field of
      nutrition during the past decade demonstrated that some feeding regimens have
      significant benefits. There is strong evidence that the use of human milk (HM)
      reduces the risk of NEC and provides major advantages in VLBW infants. The
      feeding of fortified HM should be promoted and HM banking should be further
      developed to allow access to pasteurized donor HM for VLBW infants with an
      insufficient intake of their own mother's milk. Early enteral feeding should be
      promoted soon after birth to enhance gastrointestinal maturation, growth and
      functional development. Continuous- or short-interval intermittent feeding seems
      to provide better gastrointestinal tolerance and faster achievement of full
      enteral feeding. Feeding advancements of 20-30 ml/kg/day in VLBW infants >=1,000
      g and of 15-25 ml/kg/day in ELBW infants are reasonable strategies. Any suspicion
      of feeding intolerance implies short-interval evaluation to decide whether
      interruption of enteral feeding or its restart after a transient interruption are
      appropriate. One should always strive for maintaining at least minimal enteral
      feeding, rather than complete interruption of enteral feeding.

PMID- 24751632
TI  - Human milk and human milk fortifiers.
AB  - Human milk contains numerous immune-protective components that protect the
      premature infant from sepsis and necrotizing enterocolitis. Because of these
      protective effects, human milk is the feeding of choice for the premature infant.
      However, human milk does not provide adequate amounts of most nutrients for
      premature infants and must therefore be supplemented (fortified) with nutrients.
      Commercially available fortifiers provide energy and most nutrients in adequate
      amounts. The exception is protein, which is present in expressed milk in highly
      variable amounts and which is not provided in sufficient amounts by most
      fortifiers. Some liquid fortifiers are higher in protein content than powder
      fortifiers and provide adequate amounts of protein.

PMID- 24751633
TI  - Approaches to growth faltering.
AB  - Postnatal growth failure remains a nearly universal complication of extreme
      prematurity. The incidence of postnatal growth failure is inversely related to
      gestational age. Unfortunately, by the time growth faltering is recognized, the
      nutrient deficits that have accumulated can be difficult, if not impossible, to
      recover. The perceived severity of illness in the first week can significantly
      impact decisions made related to early nutritional support. It is becoming
      increasingly clear that optimizing nutrient intake in the first few weeks of life
      is critical to reduce growth faltering. In order to promote growth and reduce
      growth faltering, a goal of 120 kcal/kg/day and 3.8 g/kg/day of protein should be
      supplied to very low birth weight infants by the end of the first week. A
      combined strategy of both parenteral and enteral nutrition is necessary to ensure
      that adequate protein and energy intake is delivered and that nutrient deficits
      are minimized. Finally, careful monitoring of growth--including both linear and
      head circumference growth--is necessary to achieve optimal outcomes.

PMID- 24751634
TI  - Preterm nutrition and the lung.
AB  - Experimental and clinical evidence show that fetal and neonatal nutrition and
      metabolism can markedly modulate pulmonary growth, development, and function, as
      well as long-term lung health and disease risks. Intrauterine growth restriction
      has been linked to an increased risk for respiratory distress syndrome and
      chronic lung disease, while excessive fetal growth reduced forced expiratory
      volume. Postnatal undernutrition adversely affected pulmonary function in animal
      models and was associated to a higher risk of chronic lung disease in very low
      birth weight infants. The supply of specific nutrients to very low birth weight
      infants, including fluids, protein, carbohydrates, inositol, docosahexaenoic
      acid, calcium, phosphorus and the vitamins A and E has been associated with lung
      development and function and deserves further evaluation. In infants with
      evolving or established chronic lung disease, excess fluid administration and
      high intravenous glucose infusion rates should be avoided and the provision of
      vitamin A be considered. Opportunities exist for further research relating to
      neonatal nutrition and lung health, for example exploring optimal strategies and
      effects of providing vitamin A, docosahexaenoic acid and intravenous lipid
      emulsions.

PMID- 24751635
TI  - Necrotizing enterocolitis.
AB  - Necrotizing enterocolitis (NEC) is the most common severe neonatal
      gastrointestinal emergency that predominantly affects premature infants. Its
      morbidity and mortality is similar to other severe childhood diseases such as
      meningitis and leukemia, and is becoming increasingly recognized as a major cause
      of neurodevelopmental delays. The etiology of NEC remains obscure despite over 40
      years of research, partly because it is more than one disease and databases
      including NEC have been diluted by these different entities. Furthermore, good
      animal models that represent the most classic form of the disease seen in preterm
      human infants are lacking. This chapter provides an overview of the
      pathophysiology, diagnosis, treatment and prevention of what has been termed
      'NEC'.

PMID- 24751636
TI  - Feeding the preterm infant after discharge.
AB  - In recent years, much attention has been focused on enhancing the nutritional
      support of very preterm infants to improve both survival and quality of life. In
      most countries throughout the world, preterm infants tend to be discharged from
      hospital earlier than the expected term for economic and other reasons. The
      question has arisen whether such infants might require special nutritional
      regimens or special discharge formulas. Since nutrition during hospitalization
      tends to improve, thereby reducing acquired nutrition deficit, the question of
      the systematic use of specially designed nutrient-enriched discharge formulas
      should be questioned. Recommendations for feeding the preterm infant after
      hospital discharge are made keeping in mind that the goal in nourishing preterm
      infants after discharge should be to promote human milk feeding, minimize
      nutrient deficits, promptly address these deficits once identified, and avoid
      over-nourishing or promoting postnatal growth acceleration once nutrient deficits
      have been corrected.

PMID- 24751638
TI  - Recommended nutrient intake levels for stable, fully enterally fed very low birth
      weight infants.
AB  - Ranges of advisable nutrient intakes are presented for populations of fully
      enterally fed very low birth weight infants, based on current evidence and an
      intensive discussion with experts in July 2013. Recommended ranges of adequate
      nutrient intakes are expressed as amounts per kilogram body weight per day and
      also per 100 kcal energy intake. For many nutrients only limited evidence exists
      at present to precisely define quantitative ranges of adequate intakes. Future
      research may lead to better knowledge and modification of recommended intake
      values.

PMID- 24751637
TI  - Meeting the challenge of providing neonatal nutritional care to very or extremely
      low birth weight infants in low-resource settings.
AB  - Most infant deaths (99%) occur in developing countries. The 14.9 million infants
      born prematurely (>11% of all live births) carry a particularly high mortality
      risk. This chapter discusses strategies to improve neonatal outcome under
      resource-restricted conditions, with a focus on nutritional interventions.
      Evidence-based interventions begin before conception with strategies to prevent
      and treat malnutrition among women of reproductive age, and micronutrient
      supplementation in pregnancy. As an example, a practically feasibly strategy of
      feeding very low birth weight infants in South Africa is presented. The use of
      parenteral nutrition can be limited by feasibility and affordability, but
      intravenous glucose and electrolytes should generally be provided after birth.
      Emphasis is put on the use of expressed own mother's milk without or with
      pasteurization from women without or with HIV infection, respectively, which is
      complemented by the use of pasteurized donor milk. If human milk fortifiers are
      not available, calcium and phosphate should be added, and high total daily feed
      volumes should be strived for, e.g. by frequent feedings. With restricted
      resources, human milk fortifiers or preterm formula can be used for high-risk
      groups such as infants with poor growth. Kangaroo mother care and breastfeeding
      should be actively encouraged.

PMID- 24751641
TI  - Marine ice regulates the future stability of a large Antarctic ice shelf.
AB  - The collapses of the Larsen A and B ice shelves on the Antarctic Peninsula in
      1995 and 2002 confirm the impact of southward-propagating climate warming in this
      region. Recent mass and dynamic changes of Larsen B's southern neighbour Larsen
      C, the fourth largest ice shelf in Antarctica, may herald a similar instability.
      Here, using a validated ice-shelf model run in diagnostic mode, constrained by
      satellite and in situ geophysical data, we identify the nature of this potential
      instability. We demonstrate that the present-day spatial distribution and
      orientation of the principal stresses within Larsen C ice shelf are akin to those
      within pre-collapse Larsen B. When Larsen B's stabilizing frontal portion was
      lost in 1995, the unstable remaining shelf accelerated, crumbled and ultimately
      collapsed. We hypothesize that Larsen C ice shelf may suffer a similar fate if it
      were not stabilized by warm and mechanically soft marine ice, entrained within
      narrow suture zones. 

PMID- 24751643
TI  - The roles of mediator complex in cardiovascular diseases.
AB  - Despite recent treatment advances, an increase in cardiovascular diseases (CVD)
      mortality is expected for the next years. Mediator (MED) complex plays key roles
      in eukaryotic gene transcription. Currently, while numerous studies have
      correlated MED alterations with several diseases, like cancer or neurological
      disorders, fewer studies have investigated MED role in CVD initiation and
      progression. The first finding of MED involvement in these pathologies was the
      correlation of missense mutations in MED13L gene with transposition of the great
      arteries. Nowadays, also MED13 and MED15 have been associated with human
      congenital heart diseases and others could be added, like MED12 that is involved
      in early mouse development and heart formation. Interestingly, a missense
      mutation in MED30 gene causes a progressive cardiomyopathy in homozygous mice
      suggesting a potential role for this subunit also in human CVDs. Moreover,
      several subunits like MED1, MED13, MED14, MED15, MED23, MED25 and CDK8 exert
      important roles in glucose and lipid metabolism. Although these evidences derive
      from in vitro and animal model studies, they indicate that their deregulation may
      have a significant role in human CVD-related metabolic disorders. Finally,
      alternative transcripts of MED12, MED19 and MED30 are differently expressed in
      circulating endothelial progenitor cells thus suggesting they can play a role in
      the field of regenerative medicine. Overall, further functional studies exploring
      MED role in human CVD are warranted. The results could allow identifying novel
      biomarkers to use in combination with imaging techniques for early diagnosis;
      otherwise, they could be useful to develop targets for novel therapeutic
      approaches. 

PMID- 24751644
TI  - Enteral nutrition in critically ill septic patients-less or more?

PMID- 24751645
TI  - Novel expression of EGFL7 in placental trophoblast and endothelial cells and its
      implication in preeclampsia.
AB  - The mammalian placenta is the site of nutrient and gas exchange between the
      mother and fetus, and is comprised of two principal cell types, trophoblasts and
      endothelial cells. Proper placental development requires invasion and
      differentiation of trophoblast cells, together with coordinated fetal
      vasculogenesis and maternal vascular remodeling. Disruption in these processes
      can result in placental pathologies such as preeclampsia (PE), a disease
      characterized by late gestational hypertension and proteinuria. Epidermal Growth
      Factor Like Domain 7 (EGFL7) is a largely endothelial-restricted secreted factor
      that is critical for embryonic vascular development, and functions by modulating
      the Notch signaling pathway. However, the role of EGFL7 in placental development
      remains unknown. In this study, we use mouse models and human placentas to begin
      to understand the role of EGFL7 during normal and pathological placentation. We
      show that Egfl7 is expressed by the endothelium of both the maternal and fetal
      vasculature throughout placental development. Importantly, we uncovered a
      previously unknown site of EGFL7 expression in the trophoblast cell lineage,
      including the trophectoderm, trophoblast stem cells, and placental trophoblasts.
      Our results demonstrate significantly reduced Egfl7 expression in human PE
      placentas, concurrent with a downregulation of Notch target genes. Moreover,
      using the BPH/5 mouse model of PE, we show that the downregulation of Egfl7 in
      compromised placentas occurs prior to the onset of characteristic maternal signs
      of PE. Together, our results implicate Egfl7 as a possible factor in normal
      placental development and in the etiology of PE. 

PMID- 24751646
TI  - Estimation of direct nonlinear effective connectivity using information theory
      and multilayer perceptron.
AB  - BACKGROUND: Despite the variety of effective connectivity measures, few methods
      can quantify direct nonlinear causal couplings and most of them are not
      applicable to high-dimensional datasets. NEW METHOD: In this paper, a novel
      approach (called betamRMR-MLP-GC) is proposed to estimate direct nonlinear
      effective connectivity of high-dimensional datasets. betamRMR is used to select a
      suitable subset of candidate regressors for approximating each neural (here EEG)
      signal. The multilayer perceptron (MLP) is used for multivariate characterization
      of EEG signals while the optimum MLP structure is selected using an iterative
      cross-validation scheme. Finally a causality measure is defined based on Granger
      Causality (GC) concept to quantify the casual relations among EEG channels.
      RESULTS: Applying betamRMR-MLP-GC to high-dimensional simulated datasets with
      different linear and nonlinear structures yields sensitivity and specificity
      values higher than 95%. Also, applying it to eyes-closed resting state EEG of six
      normal subjects in the alpha frequency band yields significant net activity
      propagations from the posterior to anterior brain regions. This is in accordance
      with the most previous studies in this field. COMPARISON WITH EXISTING METHOD(S):
      betamRMR-MLP-GC is compared with Granger Causality Index, Conditional Granger
      Causality Index, and Transfer Entropy. It outperforms these methods in terms of
      sensitivity and specificity in simulated datasets. Also, betamRMR-MLP-GC detects
      the most number of significant and reproducible Back-to-Front net information
      flows among the specified brain regions and highlights the posterior brain
      regions as dominant source of alpha activity propagation. CONCLUSIONS: betamRMR
      MLP-GC provides a novel tool to estimate the direct nonlinear causal networks of
      high-dimensional datasets.

PMID- 24751647
TI  - Decision tree structure based classification of EEG signals recorded during two
      dimensional cursor movement imagery.
AB  - BACKGROUND: Input signals of an EEG based brain computer interface (BCI) system
      are naturally non-stationary, have poor signal to noise ratio, depend on physical
      or mental tasks and are contaminated with various artifacts such as external
      electromagnetic waves, electromyogram and electrooculogram. All these
      disadvantages have motivated researchers to substantially improve speed and
      accuracy of all components of the communication system between brain and a BCI
      output device. NEW METHOD: In this study, a fast and accurate decision tree
      structure based classification method was proposed for classifying EEG data to
      up/down/right/left computer cursor movement imagery EEG data. The data sets were
      acquired from three healthy human subjects in age group of between 24 and 29
      years old in two sessions on different days. RESULTS: The proposed decision tree
      structure based method was successfully applied to the present data sets and
      achieved 55.92%, 57.90% and 82.24% classification accuracy rate on the test data
      of three subjects. COMPARISON WITH EXISTING METHOD(S): The results indicated that
      the proposed method provided 12.25% improvement over the best results of the most
      closely related studies although the EEG signals were collected on two different
      sessions with about 1 week interval. CONCLUSIONS: The proposed method required
      only a training set of the subject and automatically generated specific DTS for
      each new subject by determining the most appropriate feature set and classifier
      for each node. Additionally, with further developments of feature extraction
      and/or classification algorithms, any existing node can be easily replaced with
      new one without breaking the whole DTS. This attribute makes the proposed method
      flexible.

PMID- 24751648
TI  - Predicting structure and stability for RNA complexes with intermolecular loop
      loop base-pairing.
AB  - RNA loop-loop interactions are essential for genomic RNA dimerization and
      regulation of gene expression. In this article, a statistical mechanics-based
      computational method that predicts the structures and thermodynamic stabilities
      of RNA complexes with loop-loop kissing interactions is described. The method
      accounts for the entropy changes for the formation of loop-loop interactions,
      which is a notable advancement that other computational models have neglected.
      Benchmark tests with several experimentally validated systems show that the
      inclusion of the entropy parameters can indeed improve predictions for RNA
      complexes. Furthermore, the method can predict not only the native structures of
      RNA/RNA complexes but also alternative metastable structures. For instance, the
      model predicts that the SL1 domain of HIV-1 RNA can form two different dimer
      structures with similar stabilities. The prediction is consistent with
      experimental observation. In addition, the model predicts two different binding
      sites for hTR dimerization: One binding site has been experimentally proposed,
      and the other structure, which has a higher stability, is structurally feasible
      and needs further experimental validation. 

PMID- 24751649
TI  - Amino acid-dependent stability of the acyl linkage in aminoacyl-tRNA.
AB  - Aminoacyl-tRNAs are the biologically active substrates for peptide bond formation
      in protein synthesis. The stability of the acyl linkage in each aminoacyl-tRNA,
      formed through an ester bond that connects the amino acid carboxyl group with the
      tRNA terminal 3'-OH group, is thus important. While the ester linkage is the same
      for all aminoacyl-tRNAs, the stability of each is not well characterized, thus
      limiting insight into the fundamental process of peptide bond formation. Here, we
      show, by analysis of the half-lives of 12 of the 22 natural aminoacyl-tRNAs used
      in peptide bond formation, that the stability of the acyl linkage is effectively
      determined only by the chemical nature of the amino acid side chain. Even the
      chirality of the side chain exhibits little influence. Proline confers the lowest
      stability to the linkage, while isoleucine and valine confer the highest, whereas
      the nucleotide sequence in the tRNA provides negligible contribution to the
      stability. We find that, among the variables tested, the protein translation
      factor EF-Tu is the only one that can protect a weak acyl linkage from
      hydrolysis. These results suggest that each amino acid plays an active role in
      determining its own stability in the acyl linkage to tRNA, but that EF-Tu
      overrides this individuality and protects the acyl linkage stability for protein
      synthesis on the ribosome. 

PMID- 24751650
TI  - Novel RNA structural features of an alternatively splicing group II intron from
      Clostridium tetani.
AB  - Group II introns are ribozymes in bacterial and organellar genomes that function
      as self-splicing introns and as retroelements. Previously, we reported that the
      group II intron C.te.I1 of Clostridium tetani alternatively splices in vivo to
      produce five distinct coding mRNAs. Accurate fusion of upstream and downstream
      reading frames requires a shifted 5' splice site located 8 nt upstream of the
      usual 5' GUGYG motif. This site is specified by the ribozyme through an altered
      intron/exon-binding site 1 (IBS1-EBS1) pairing. Here we use mutagenesis and self
      splicing assays to investigate in more detail the significance of the structural
      features of the C.te.I1 ribozyme. The shifted 5' splice site is shown to be
      affected by structures in addition to IBS1-EBS1, and unlike other group II
      introns, C.te.I1 appears to require a spacer between IBS1 and the GUGYG motif. In
      addition, the mechanism of 3' exon recognition is modified from the ancestral IIB
      mechanism to a IIA-like mechanism that appears to be longer than the typical
      single base-pair interaction and may extend up to 4 bp. The novel ribozyme
      properties that have evolved for C.te.I1 illustrate the plasticity of group II
      introns in adapting new structural and catalytic properties that can be utilized
      to affect gene expression. 

PMID- 24751651
TI  - Translation control of TAK1 mRNA by hnRNP K modulates LPS-induced macrophage
      activation.
AB  - Macrophage activation by bacterial lipopolysaccharides (LPS) is induced through
      Toll-like receptor 4 (TLR4). The synthesis and activity of TLR4 downstream
      signaling molecules modulates the expression of pro- and anti-inflammatory
      cytokines. To address the impact of post-transcriptional regulation on that
      process, we performed RIP-Chip analysis. Differential association of mRNAs with
      heterogeneous nuclear ribonucleoprotein K (hnRNP K), an mRNA-specific
      translational regulator in differentiating hematopoietic cells, was studied in
      noninduced and LPS-activated macrophages. Analysis of interactions affected by
      LPS revealed several mRNAs encoding TLR4 downstream kinases and their modulators.
      We focused on transforming growth factor-beta-activated kinase 1 (TAK1) a central
      player in TLR4 signaling. HnRNP K interacts specifically with a sequence in the
      TAK1 mRNA 3' UTR in vitro. Silencing of hnRNP K does not affect TAK1 mRNA
      synthesis or stability but enhances TAK1 mRNA translation, resulting in elevated
      TNF-alpha, IL-1beta, and IL-10 mRNA expression. Our data suggest that the hnRNP K
      3' UTR complex inhibits TAK1 mRNA translation in noninduced macrophages. LPS
      dependent TLR4 activation abrogates translational repression and newly
      synthesized TAK1 boosts macrophage inflammatory response. 

PMID- 24751652
TI  - Palmitoylation of the immunity related GTPase, Irgm1: impact on membrane
      localization and ability to promote mitochondrial fission.
AB  - The Immunity-Related GTPases (IRG) are a family of large GTPases that mediate
      innate immune responses. Irgm1 is particularly critical for immunity to bacteria
      and protozoa, and for inflammatory homeostasis in the intestine. Although precise
      functions for Irgm1 have not been identified, prior studies have suggested roles
      in autophagy/mitophagy, phagosome remodeling, cell motility, and regulating the
      activity of other IRG proteins. These functions ostensibly hinge on the ability
      of Irgm1 to localize to intracellular membranes, such as those of the Golgi
      apparatus and mitochondria. Previously, it has been shown that an amphipathic
      helix, the alphaK helix, in the C-terminal portion of the protein partially
      mediates membrane binding. However, in absence of alphaK, there is still
      substantial binding of Irgm1 to cellular membranes, suggesting the presence of
      other membrane binding motifs. In the current work, an additional membrane
      localization motif was found in the form of palmitoylation at a cluster of
      cysteines near the alphaK. An Irgm1 mutant possessing alanine to cysteine
      substitutions at these amino acids demonstrated little residual palmitoylation,
      yet it displayed only a small decrease in localization to the Golgi and
      mitochondria. In contrast, a mutant containing the palmitoylation mutations in
      combination with mutations disrupting the amphipathic character of the alphaK
      displayed a complete loss of apparent localization to the Golgi and mitochondria,
      as well as an overall loss of association with cellular membranes in general.
      Additionally, Irgm1 was found to promote mitochondrial fission, and this function
      was undermined in Irgm1 mutants lacking the palmitoylation domain, and to a
      greater extent in those lacking the alphaK, or the alphaK and palmitoylation
      domains combined. Our data suggest that palmitoylation together with the alphaK
      helix firmly anchor Irgm1 in the Golgi and mitochondria, thus facilitating
      function of the protein. 

PMID- 24751653
TI  - Adipose tissue-derived human serum amyloid a does not affect atherosclerotic
      lesion area in hSAA1+/-/ApoE-/- mice.
AB  - Chronically elevated serum levels of serum amyloid A (SAA) are linked to
      increased risk of cardiovascular disease. However, whether SAA is directly
      involved in atherosclerosis development is still not known. The aim of this study
      was to investigate the effects of adipose tissue-derived human SAA on
      atherosclerosis in mice. hSAA1+/- transgenic mice (hSAA1 mice) with a specific
      expression of human SAA1 in adipose tissue were bred with ApoE-deficient mice.
      The hSAA1 mice and their wild type (wt) littermates were fed normal chow for 35
      weeks. At the end of the experiment, the mice were euthanized and blood, gonadal
      adipose tissue and aortas were collected. Plasma levels of SAA, cholesterol and
      triglycerides were measured. Atherosclerotic lesion areas were analyzed in the
      aortic arch, the thoracic aorta and the abdominal aorta in en face preparations
      of aorta stained with Sudan IV. The human SAA protein was present in plasma from
      hSAA1 mice but undetectable in wt mice. Similar plasma levels of cholesterol and
      triglycerides were observed in hSAA1 mice and their wt controls. There were no
      differences in atherosclerotic lesion areas in any sections of the aorta in hSAA1
      mice compared to wt mice. In conclusion, our data suggest that adipose tissue
      derived human SAA does not influence atherosclerosis development in mice. 

PMID- 24751654
TI  - Imaging of naive myopic choroidal neovascularization by spectral-domain optical
      coherence tomography.
AB  - PURPOSE: To assess the tomographic features of myopic choroidal
      neovascularization by spectral-domain optical coherence tomography. METHODS: We
      consecutively reviewed the charts of patients with pathologic myopia, recent
      visual acuity deterioration and active macular neovascularization. Specific
      tomographic changes were studied in 25 eyes by two authors independently.
      RESULTS: The mean age of patients eligible for the study was 63.4 (+/- 18.2)
      years. Main tomographic outcomes were the hyperreflectivity of the lesion in 88%
      of cases (95% CI 0.74-1.02), absence of the external limiting membrane in 88%
      (95% CI 0.84-1.02), and retinal thickening in 83% (95% CI 0.67-0.99). The
      internal plexiform layer remained discernible in 83% (95% CI 0.67-0.99) of cases,
      the inner nuclear layer in 62% (95% CI 0.37-0.80), the external plexiform layer
      in 48% (95% CI 0.27-0.69). Retinal edema was noted in 48% (95% CI 0.26-0.70) of
      patients. CONCLUSIONS: Myopic choroidal neovascularization appears predominantly
      hyperreflective, causes thickening of the corresponding retina and mainly
      involves the external retinal segments. Retinal fluid is infrequent.

PMID- 24751655
TI  - Family nutrition program assistants' perception of farmers' markets, alternative
      agricultural practices, and diet quality.
AB  - OBJECTIVE: To explore Family Nutrition Program assistants' perception of farmers'
      markets and alternative agricultural practices for themselves and their clients.
      METHODS: Cross-section design, survey of Virginia Expanded Food and Nutrition
      Education Program (NEP) and Supplemental Nutrition Assistance Program-Education
      Family Nutrition Program assistants (n = 52) working with limited-resource
      populations. RESULTS: Twenty-one percent to 55% of FNP assistants valued
      alternative agricultural practices, and only 5% to 8% of FNP assistants perceived
      that their clients did so. Benefits to shopping at farmers' markets included
      supporting local economies, and food price, quality, and safety. Barriers
      included lack of transportation, location/convenience, hours, and food prices.
      Assistants rated the benefits to shopping at farmers' markets similarly for
      themselves and their clients, but rated many of the barriers to shopping at
      farmers' markets as significantly lower (P < .05) for themselves than for their
      clients. CONCLUSIONS AND IMPLICATIONS: Future assistant trainings should address
      the connection between agriculture and health, and how to overcome barriers to
      shopping at farmers' markets for their clients.

PMID- 24751657
TI  - Muscle activation does not increase after a fatigue plateau is reached during 8
      sets of resistance exercise in trained individuals.
AB  - The premise of eliciting the greatest acute fatigue is accepted and used for
      designing programs that include excessive, potentially dangerous volumes of high
      intensity resistance exercise. There is no evidence examining acute fatigue and
      neuromuscular responses throughout multiple sets of moderate-to-high intensity
      resistance exercise. Fifteen resistance-trained male subjects performed a single
      exercise session using 8 sets of Bulgarian split squats performed at 75% maximal
      force output. Maximal force output (N) was measured after every set of
      repetitions. Electromyographic (EMG) activity of vastus lateralis was monitored
      during all force trials and exercise repetitions. Repetitions per set decreased
      from the first to the third set (p < 0.001). Maximal force output decreased from
      preexercise to set 4 (p < 0.001). Electromyographic amplitudes during exercise
      did not change. Secondary subgroup analysis was performed based on the presence,
      or not, of a fatigue plateau (<5% reductions in maximal force output in
      subsequent sets). Nine participants exhibited a fatigue plateau, and 6 did not.
      Participants who plateaued performed less first-set repetitions, accrued less
      total volume, and did not exhibit increases in EMG amplitudes during exercise.
      Initial strength levels and neuromuscular demand of the exercise was the same
      between the subgroups. These data suggest that there are individual differences
      in the training session responses when prescribing based off a percentage of
      maximal strength. When plateaus in fatigue and repetitions per set are reached,
      subsequent sets are not likely to induce greater fatigue and muscle activation.
      High-volume resistance exercise should be carefully prescribed on an individual
      basis, with intrasession technique and training responsiveness continually
      monitored.

PMID- 24751656
TI  - Effects of compliance on trunk and hip integrative neuromuscular training on hip
      abductor strength in female athletes.
AB  - Recent studies demonstrate the link between reduced hip abductor strength and
      increased risk for knee injury such as patellofemoral pain syndrome in women
      athletes. Meta-analytic reports indicate that the efficacy of integrative
      neuromuscular training (INT) is associated with compliance to the prescribed
      programming. Thus, the purpose was to investigate the compliance effects of a
      trunk and hip-focused INT exercises on hip abductor strength in young women
      athletes. In a controlled laboratory study design, 21 high school women
      volleyball players (mean age = 15.6 +/- 1.4 years, weight = 64.0 +/- 7.4 kg,
      height = 171.5 +/- 7.0 cm) completed isokinetic hip abductor strength testing in
      pre- and postintervention, which consisted of 5 phases of supervised progressive
      trunk and hip-focused INT exercises twice a week for 10 weeks. The compliance
      effects were analyzed based on the changed hip abductor strength values between
      pre- and postintervention and 3 different compliance groups using 1-way analysis
      of variance and Pearson's correlation coefficients. The participants in the high
      compliance group demonstrated significant hip abductor peak torque increases
      compared with noncompliance group (p = 0.02), but not between moderate-compliance
      and noncompliance groups (p = 0.27). The moderate correlation coefficient value
      (r = 0.56) was recorded between the isokinetic hip abductor peak torque changes
      and the 3 compliance groups. Because of the observed significant effects and
      moderate linear association, the effectiveness of a trunk and hip-focused INT
      protocol to improve hip abduction strength seems dependent on compliance.
      Compliance of trunk and hip-focused INT is an important aspect of increasing hip
      abductor strength increase in young women athletes.

PMID- 24751658
TI  - Effects of in-season low-volume high-intensity plyometric training on explosive
      actions and endurance of young soccer players.
AB  - Integrating specific training methods to improve explosive actions and endurance
      in youth soccer is an essential part of players' development. This study
      investigated the efficiency of short-term vertical plyometric training program
      within soccer practice to improve both explosive actions and endurance in young
      soccer players. Seventy-six players were recruited and assigned either to a
      training group (TG; n = 38; 13.2 +/- 1.8 years) or a control group (CG; n = 38;
      13.2 +/- 1.8 years) group. All players trained twice per week, but the TG
      followed a 7-week plyometric program implemented within soccer practice, whereas
      the CG followed regular practice. Twenty-meter sprint time (20-m), Illinois
      agility test time, countermovement jump (CMJ) height, 20- (RSI20) and 40- (RSI40)
      cm drop jump reactive strength index, multiple 5 bounds distance (MB5), maximal
      kicking test for distance (MKD), and 2.4-km time trial were measured before and
      after the 7-week period. Plyometric training induced significant (p <= 0.05) and
      small to moderate standardized effect (SE) improvement in the CMJ (4.3%; SE =
      0.20), RSI20 (22%; SE = 0.57), RSI40 (16%; SE = 0.37), MB5 (4.1%; SE = 0.28),
      Illinois agility test time (-3.5%, SE = -0.26), MKD (14%; SE = 0.53), 2.4-km time
      trial (-1.9%; SE = -0.27) performances but had a trivial and nonsignificant
      effect on 20-m sprint time (-0.4%; SE = -0.03). No significant improvements were
      found in the CG. An integrated vertical plyometric program within the regular
      soccer practice can substitute soccer drills to improve most explosive actions
      and endurance, but horizontal exercises should also be included to enhance
      sprinting performance.

PMID- 24751659
TI  - The association between the history of cardiovascular diseases and chronic low
      back pain in South Koreans: a cross-sectional study.
AB  - BACKGROUND: Cardiovascular disease and related risk factors have been suggested
      as a mechanism leading to atherosclerosis of the lumbar vessels and consequent
      lumbar pain or sciatica. But there is continued controversy concerning its
      generalization. This study examined whether cardiovascular disease or its risk
      factors were associated with chronic low back pain (cLBP) in Koreans. METHODS:
      Health surveys and examinations were conducted on a nationally representative
      sample (n = 23,632) of Koreans. A total of 13,841 eligible participants (aged 20
      to 89 years) were examined to determine the association between cardiovascular
      disease, the Framingham risk score, major cardiovascular risk factors (blood
      pressure, diabetes, cholesterol, and smoking habits) and chronic LBP. RESULTS:
      The total prevalence of cLBP was 16.6% (men: 10.8%, women: 21.1%) and that in
      patients with a history of cardiovascular diseases was 36.6% (men: 26.5%, women:
      47.1%). The results showed that patients' medical history of cardiovascular
      disease was significantly associated with cLBP in both men and women when
      adjusted for covariates (men: OR 2.16; 95%CI 1.34~3.49; women: OR 2.26; 95%CI
      1.51~3.38). No association was observed between cLBP and the Framingham risk
      score, medication for hyperlipemia, hypertension, diabetes, and major
      cardiovascular risk factors (systolic blood pressure, total cholesterol, high
      density lipoprotein cholesterol, triglycerides, glucose and smoking habits) in
      either men or women. CONCLUSIONS: The prevalence of cLBP is correlated to a
      history of cardiovascular disease, but not to the major cardiovascular risk
      factors from the Framingham study. Further studies on whether these results were
      affected by psychological factors in patients with a history of cardiovascular
      diseases or whether new potential risk factors from the artery atherosclerosis
      hypothesis applying to Koreans exist are needed.

PMID- 24751660
TI  - Direct evidence on the contribution of a missense mutation in GDF9 to variation
      in ovulation rate of Finnsheep.
AB  - The Finnish Landrace (Finnsheep) is a well known high-prolificacy sheep breed and
      has been used in many countries as a source of genetic material to increase
      fecundity of local breeds. Analyses to date have indicated that mutations with a
      large effect on ovulation rate are not responsible for the exceptional
      prolificacy of Finnsheep. The objectives of this study were to ascertain if: 1)
      any of 12 known mutations with large effects on ovulation rate in sheep, or 2)
      any other DNA sequence variants within the candidate genes GDF9 and BMP15 are
      implicated in the high prolificacy of the Finnish Landrace breed; using material
      from lines developed by divergent selection on ovulation rate. Genotyping results
      showed that none of 12 known mutations (FecBB, FecXB, FecXG, FecXGR, FecXH,
      FecXI, FecXL, FecXO, FecXR, FecGE, FecGH, or FecGT) were present in a sample of
      108 Finnsheep and, thus, do not contribute to the exceptional prolificacy of the
      breed. However, DNA sequence analysis of GDF9 identified a previously known
      mutation, V371M, whose frequency differed significantly (P<0.001) between High
      and Low ovulation rate lines. While analysis of ovulation rate data for Finnsheep
      failed to establish a significant association between this trait and V371M,
      analysis of data on Belclare sheep revealed a significant association between
      V371M and ovulation rate (P<0.01). Ewes that were heterozygous for V371M
      exhibited increased ovulation rate (+0.17, s.e. 0.080; P<0.05) compared to wild
      type and the effect was non-additive (ovulation rate of heterozygotes was
      significantly lower (P<0.01) than the mean of the homozygotes). This finding
      brings to 13 the number of mutations that have large effects on ovulation rate in
      sheep and to 5, including FecBB, FecGE, FecXO and FecXGR, the number of mutations
      within the TGFbeta superfamily with a positive effect on prolificacy in the
      homozygous state. 

PMID- 24751661
TI  - Identification of a novel retrotransposon with sex chromosome-specific
      distribution in Silene latifolia.
AB  - Silene latifolia is a dioecious plant species with chromosomal sex determination.
      Although the evolution of sex chromosomes in S. latifolia has been the subject of
      numerous studies, a global view of X chromosome structure in this species is
      still missing. Here, we combine X chromosome microdissection and BAC library
      screening to isolate new X chromosome-linked sequences. Out of 8 identified BAC
      clones, only BAC 86M14 showed an X-preferential signal after FISH experiments.
      Further analysis revealed the existence of the Athila retroelement which is
      enriched in the X chromosome and nearly absent in the Y chromosome. Based on
      previous data, the Athila retroelement belongs to the CL3 group of most
      repetitive sequences in the S. latifolia genome. Structural, transcriptomics and
      phylogenetic analyses revealed that Athila CL3 represents an old clade in the
      Athila lineage. We propose a mechanism responsible for Athila CL3 distribution in
      the S. latifolia genome.

PMID- 24751662
TI  - Comparative evaluation of peptide desalting methods for salivary proteome
      analysis.
AB  - BACKGROUND: Reliability and reproducibility are common requirements for high
      quality generation of proteome data using mass spectrometry. The aim of this
      study was to compare four single-step desalting devices to provide a
      reproducible, high-recovery method for concentrating and purifying tryptic
      peptides before LC-MS/MS measurements. MATERIAL AND METHODS: Four different
      methods for peptide purification prior LC-MS/MS analyses (MUC18 ZipTip(r) pipette
      tips, C18 ZipTip(r) pipette tips, TopTip C-18 and OASIS(r) HLB MUElution Plate)
      were tested using whole saliva from healthy volunteers. A number of protein
      identifications and salivary protein patterns were analyzed comparatively.
      RESULTS: Each desalting device facilitated the identification of about 340
      proteins. Purification-method dependent variations in protein composition were
      observed. Nevertheless, the overall inter-approach Pearson correlation
      coefficients of >0.95 indicate high reproducibility, reliability and recovery of
      proteins. CONCLUSION: The applied devices performed equally well in the removal
      of low molecular weight contaminants and provide high-quality data for
      quantitative proteomic analysis. Thus, selection should be primarily based on the
      amount of peptide extract available and the number of samples to be processed.

PMID- 24751663
TI  - Reliability and validity of digital imaging as a measure of schoolchildren's
      fruit and vegetable consumption.
AB  - BACKGROUND: As more and more interventions aim to increase schoolchildren's fruit
      and vegetable (FV) consumption, less resource-intensive yet valid alternatives to
      weighed plate waste (WPW) are needed for assessing dietary intake. OBJECTIVES: We
      aimed to test the reliability and validity of digital imaging (DI) and digital
      imaging with observation (DI+O) in assessing children's FV consumption during
      school lunch. DESIGN: FV consumption (in grams) was assessed on lunch trays from
      third- to fifth-grade children over eight visits (31 to 68 trays collected per
      visit) to compare WPW with DI and DI+O. SETTING: Two elementary schools (327 and
      631 students enrolled, respectively). MAIN OUTCOME MEASURES: Interobserver
      reliability of DI. Validity of DI and DI+O compared against WPW. STATISTICAL
      ANALYSES: Reliability was assessed by percent agreement and intraclass
      correlation coefficients (ICCs). Validity was assessed by Pearson correlations,
      paired t tests, and Bland-Altman plots. RESULTS: Reliability was acceptable for
      DI; percent agreement was 96% and the ICC was 0.92. FV consumption assessments by
      DI and WPW (n=159) were highly correlated (r=0.96; P<0.001). Mean FV consumption
      using DI (96.7 g) was within 1.0 g of WPW and not significantly different from
      WPW (P=0.56), and Bland-Altman limits of agreement for individual-tray FV
      consumption were -32.9 to 31.3 g. FV consumption assessments by DI+O and WPW were
      highly correlated (r=0.98; P<0.001). Mean FV consumption using DI+O (99.3 g) was
      within 1.0 g of WPW and not significantly different from WPW (P=0.38), and limits
      of agreement for individual-tray FV consumption were -25.0 to 26.8 g.
      CONCLUSIONS: DI was reliable for assessing children's FV consumption during
      school lunch. DI and DI+O were valid for assessing mean consumption but less
      precise for estimating individual-tray consumption. Valid estimations of mean FV
      consumption were achieved using DI without cafeteria observations, thereby
      reducing labor and time. Thus, DI is especially promising for assessing
      children's mean FV consumption during school lunch.

PMID- 24751664
TI  - Vegetable output and cost savings of community gardens in San Jose, California.
AB  - Urban dwellers across the United States increasingly access a variety of fresh
      vegetables through participation in neighborhood-level community gardens. Here we
      document vegetable output and cost savings of community gardens in the city of
      San Jose, CA, to better understand the capacity of community gardens to affect
      food affordability in an urban setting. A convenience sample of 83 community
      gardeners in San Jose completed a background survey during spring and summer
      2012. On average, gardeners were aged 57 years and had a monthly income of
      $4,900; 25% had completed college. A representative subset of 10 gardeners was
      recruited to weigh vegetable output of their plots using portable electronic
      scales at three separate garden sites. Accuracy of each portable scale was
      verified by comparing the weight of a sample vegetable to weights obtained using
      a lab scale precise to 0.2 oz. Garden yields and cost savings were tabulated
      overall for each plot. Results indicate that community garden practices are more
      similar to biointensive high-production farming, producing 0.75 lb vegetables/sq
      ft, rather than conventional agricultural practices, producing 0.60 lb/sq ft.
      Gardens produced on average 2.55 lb/plant and saved $435 per plot for the season.
      Results indicate that cost savings are greatest if vertical high value crops such
      as tomatoes and peppers are grown in community gardens, although yields depend on
      growing conditions, gardener's skill, availability of water, and other factors.
      Future research is needed to document cost savings and yields for specific crops
      grown in community gardens.

PMID- 24751666
TI  - Exploring disparities in acute myocardial infarction events between Aboriginal
      and non-Aboriginal Australians: roles of age, gender, geography and area-level
      disadvantage.
AB  - We investigated disparities in rates of acute myocardial infarction (AMI) between
      Aboriginal and non-Aboriginal people in the 199 Statistical Local Areas (SLAs) in
      New South Wales, Australia. Using routinely collected and linked hospital and
      mortality data from 2002 to 2007, we developed multilevel Poisson regression
      models to estimate the relative rates of first AMI events in the study period
      accounting for area of residence. Rates of AMI in Aboriginal people were more
      than two times that in non-Aboriginal people, with the disparity greatest in more
      disadvantaged and remote areas. AMI rates in Aboriginal people varied
      significantly by SLA, as did the Aboriginal to non-Aboriginal rate ratio. We
      identified almost 30 priority areas for universal and targeted preventive
      interventions that had both high rates of AMI for Aboriginal people and large
      disparities in rates. 

PMID- 24751665
TI  - A high-performance thioredoxin-based scaffold for peptide immunogen construction:
      proof-of-concept testing with a human papillomavirus epitope.
AB  - Escherichia coli thioredoxin has been previously exploited as a scaffold for the
      presentation/stabilization of peptide aptamers as well as to confer
      immunogenicity to peptide epitopes. Here we focused on other key features of
      thioredoxin that are of general interest for the production of safer and more
      effective peptide immunogens, such as a high thermal stability, lack of cross
      reactivity and a low-cost of production. We identified thioredoxin from the
      archaebacterium Pyrococcus furiosus (PfTrx) as a novel scaffold meeting all the
      above criteria. PfTrx is a highly thermostable and protease-resistant scaffold
      with a strong (poly)peptide solubilisation capacity. Anti-PfTrx antibodies did
      not cross-react with mouse, nor human thioredoxin. Untagged PfTrx bearing a
      previously identified HPV16-L2 peptide epitope was obtained in a >90% pure form
      with a one-step thermal purification procedure and effectively elicited the
      production of neutralizing anti-HPV antibodies. We thus propose PfTrx as a
      superior, general-purpose scaffold for the construction of safe, stable, and low
      cost peptide immunogens. 

PMID- 24751667
TI  - Incorporation of ortho- and meta-tyrosine into cellular proteins leads to
      erythropoietin-resistance in an erythroid cell line.
AB  - BACKGROUND/AIMS: Erythropoietin-resistance is an unsolved concern in the
      treatment of renal anaemia. We aimed to investigate the possible role of ortho-
      and meta-tyrosine - the hydroxyl free radical products of L-phenylalanine - in
      the development of erythropoietin-resistance. METHODS: TF-1 erythroblast cell
      line was used. Cell concentration was determined on day 1; 2 and 3 by two
      independent observers simultaneously in Burker cell counting chambers. Protein
      concentration was determined with colorimetric method. Para-, ortho- and meta
      tyrosine levels were measured using reverse phase-HPLC with fluorescence
      detection. Using Western blot method activating phosphorylation of STAT5 and
      ERK1/2 were investigated. RESULTS: We found a time- and concentration-dependent
      decrease of erythropoietin-induced proliferative activity in case of ortho- and
      meta-tyrosine treated TF-1 erythroblasts, compared to the para-tyrosine cultured
      cells. Decreased erythropoietin-response could be regained with a competitive
      dose of para-tyrosine. Proteins of erythroblasts treated by ortho- or meta
      tyrosine had lower para-tyrosine and higher ortho- or meta-tyrosine content.
      Activating phosphorylation of ERK and STAT5 due to erythropoietin was practically
      prevented by ortho- or meta-tyrosine treatment. CONCLUSION: According to this
      study elevated ortho- and meta-tyrosine content of erythroblasts may lead to the
      dysfunction of intracellular signaling, resulting in erythropoietin
      hyporesponsiveness.

PMID- 24751668
TI  - Omeprazole-induced drug reaction with eosinophilia and systemic symptoms (DRESS).

PMID- 24751669
TI  - Defect-induced plating of lithium metal within porous graphene networks.
AB  - Lithium metal is known to possess a very high theoretical capacity of 3,842 mAh
      g(-1) in lithium batteries. However, the use of metallic lithium leads to
      extensive dendritic growth that poses serious safety hazards. Hence, lithium
      metal has long been replaced by layered lithium metal oxide and phospho-olivine
      cathodes that offer safer performance over extended cycling, although
      significantly compromising on the achievable capacities. Here we report the
      defect-induced plating of metallic lithium within the interior of a porous
      graphene network. The network acts as a caged entrapment for lithium metal that
      prevents dendritic growth, facilitating extended cycling of the electrode. The
      plating of lithium metal within the interior of the porous graphene structure
      results in very high specific capacities in excess of 850 mAh g(-1). Extended
      testing for over 1,000 charge/discharge cycles indicates excellent reversibility
      and coulombic efficiencies above 99%.

PMID- 24751670
TI  - Mitochondrial genomes of Meloidogyne chitwoodi and M. incognita (Nematoda:
      Tylenchina): comparative analysis, gene order and phylogenetic relationships with
      other nematodes.
AB  - Root-knot nematodes (Meloidogyne spp.) are among the most important plant
      pathogens. In this study, the mitochondrial (mt) genomes of the root-knot
      nematodes, M. chitwoodi and M. incognita were sequenced. PCR analyses suggest
      that both mt genomes are circular, with an estimated size of 19.7 and 18.6
      19.1kb, respectively. The mt genomes each contain a large non-coding region with
      tandem repeats and the control region. The mt gene arrangement of M. chitwoodi
      and M. incognita is unlike that of other nematodes. Sequence alignments of the
      two Meloidogyne mt genomes showed three translocations; two in transfer RNAs and
      one in cox2. Compared with other nematode mt genomes, the gene arrangement of M.
      chitwoodi and M. incognita was most similar to Pratylenchus vulnus. Phylogenetic
      analyses (Maximum Likelihood and Bayesian inference) were conducted using 78
      complete mt genomes of diverse nematode species. Analyses based on nucleotides
      and amino acids of the 12 protein-coding mt genes showed strong support for the
      monophyly of class Chromadorea, but only amino acid-based analyses supported the
      monophyly of class Enoplea. The suborder Spirurina was not monophyletic in any of
      the phylogenetic analyses, contradicting the Clade III model, which groups
      Ascaridomorpha, Spiruromorpha and Oxyuridomorpha based on the small subunit
      ribosomal RNA gene. Importantly, comparisons of mt gene arrangement and tree
      based methods placed Meloidogyne as sister taxa of Pratylenchus, a migratory
      plant endoparasitic nematode, and not with the sedentary endoparasitic
      Heterodera. Thus, comparative analyses of mt genomes suggest that sedentary
      endoparasitism in Meloidogyne and Heterodera is based on convergent evolution. 

PMID- 24751671
TI  - Calorimetric investigation of diclofenac drug binding to a panel of moderately
      glycated serum albumins.
AB  - Glycation alters the drug binding properties of serum proteins and could affect
      free drug concentrations in diabetic patients with elevated glycation levels. We
      investigated the effect of bovine serum albumin glycation by eight
      physiologically relevant glycation reagents (glucose, ribose,
      carboxymethyllysine, acetoin, methylglyoxal, glyceraldehyde, diacetyl and
      glycolaldehyde) on diclofenac drug binding. We used this non-steroidal anti
      inflammatory drug diclofenac as a paradigm for acidic drugs with high serum
      binding and because of its potential cardiovascular risks in diabetic patients.
      Isothermal titration calorimetry showed that glycation reduced the binding
      affinity Ka of serum albumin and diclofenac 2 to 6-fold by reducing structural
      rigidity of albumin. Glycation affected the number of drug binding sites in a
      glycation reagent dependent manner and lead to a 25% decrease for most reagent,
      expect for ribose, with decreased by 60% and for the CML-modification, increased
      the number of binding sites by 60%. Using isothermal titration calorimetry and
      differential scanning calorimetry we derived the complete thermodynamic
      characterization of diclofenac binding to all glycated BSA samples. Our results
      suggest that glycation in diabetic patients could significantly alter the
      pharmacokinetics of the widely used over-the-counter NSDAI drug diclofenac and
      with possibly negative implications for patients. 

PMID- 24751672
TI  - Viscosity-mediated negative food effect on oral absorption of poorly-permeable
      drugs with an absorption window in the proximal intestine: In vitro experimental
      simulation and computational verification.
AB  - Concomitant food intake can diminish oral absorption of drugs with limited
      permeability and an absorption window in the proximal intestine, due to viscosity
      mediated decrease in dosage form disintegration time and drug dissolution rate.
      Three poorly-permeable drugs (atenolol, metformin hydrochloride, and furosemide)
      exhibiting negative food effect, and one highly-soluble and highly-permeable
      (metoprolol tartrate), serving as a negative control, were selected for the
      study. In vitro and in silico tools were used to evaluate the influence of media
      viscosity on drug bioperformance under fasted and fed conditions. The obtained
      results demonstrated that increased medium viscosity in the presence of food is
      one of the key factors limiting oral absorption of drugs with limited
      permeability and absorption restricted to the upper parts of the intestine, while
      having negligible effect on pharmacokinetic profile of drugs with pH- and site
      independent absorption. Dissolution medium pH 4.6 with the addition of
      hydroxypropyl methylcellulose was suggested to simulate postprandial gastric
      conditions for drugs whose solubility under these conditions is not the limiting
      factor for drug absorption. In addition, drug formulation was found to be an
      interfering factor in relation to the impact of medium viscosity on the rate and
      extent of drug absorption.

PMID- 24751674
TI  - Gene delivery to carcinoma cells via novel non-viral vectors: nanoparticle
      tracking analysis and suicide gene therapy.
AB  - Suicide gene therapy of oral squamous cell carcinoma (OSCC) may be a viable
      approach to the treatment of this cancer. However, human OSCC cells are
      relatively resistant to efficient transfection by non-viral vectors. To identify
      an optimal vector for gene delivery, we compared the transfection activities and
      efficiencies of Glycofect, Metafectene, Metafectene Pro, Metafectene Easy and
      FuGENE HD, using the OSCC cell line, HSC-3, and the cervical carcinoma cell line,
      HeLa. The size distribution and zeta-potential of the complexes of these vectors
      with plasmid DNA were assessed by nanoparticle tracking analysis and
      electrophoretic mobility measurements, respectively. Metafectene Easy and FuGENE
      HD mediated the highest transfection activity (measured as luciferase expression)
      and efficiency (measured as the percentage of cells transfected with beta
      galactosidase). These vectors were used to deliver a plasmid encoding herpes
      simplex virus thymidine kinase, followed by ganciclovir treatment. By day 9, HeLa
      cell viability was 22+/-3% of controls with FuGENE HD and 26+/-3% with
      Metafectene Easy. The viability of HSC-3 cells was 42+/-25% with FuGENE HD, and
      58+/-28% with Metafectene Easy. The reduction in viability was statistically
      significant in both cases (p?0.005; average of 3 independent experiments),
      although there was considerable variability between experiments with the HSC-3
      cells. 

PMID- 24751675
TI  - The value of a medical student radiology triage program in enhancing clinical
      education and skills.
AB  - RATIONALE AND OBJECTIVES: The Medical Student Radiology Triage Program (MSRTP) at
      Dartmouth-Hitchcock Medical Center recruits third- and fourth-year medical
      students to streamline imaging workflow for on-call radiology residents. We
      sought to evaluate the benefit of this program for improving medical student
      education. MATERIALS AND METHODS: Members of the program were surveyed
      anonymously from 2010 to 2012 using a web-based survey. The survey asked the
      students to rate the program in several categories from 1 (very poor) to 5 (very
      good). Students also indicated if they are learning any of the identified skills.
      RESULTS: Thirty of 54 (56%) former and current members responded to the survey.
      Support from on-call residents (mean rating 4.7) and interactions with residents
      (mean rating 4.7) were rated the highest of the categories. Students ranked
      training provided (4.2), interactions with technologists (4.2), and interactions
      with clinicians (4.1) the lowest. The medical training experience and overall
      experience were graded with means of 4.4 and 4.5, respectively. Ninety-six
      percent of students felt they acquired triaging skills, whereas 92% of students
      developed communication skills. Sixty-nine and sixty-two percent of students
      stated that they gained radiologic knowledge and general medical knowledge,
      respectively. Sixty-five and fifty percent of students developed imaging
      appropriateness criteria and image interpretation skills, respectively. The most
      popular reason for joining the program was for financial compensation (number of
      students = 12), followed by exposure to radiology (n = 8), radiology education (n
      = 8), and clinical exposure (n = 7). Major strengths of the program included
      interactions with residents, learning experience, and triaging of workflow.
      Students listed the top two problems with the program as computed tomography
      technologists and clinicians not wanting to speak to them. CONCLUSIONS: The MSRTP
      serves as a valuable clinical learning experience as well as being highly
      beneficial to resident workflows on call. Participants of MSRTP gain clinical
      skills that they will use during residency.

PMID- 24751673
TI  - Dose-response-time data analysis involving nonlinear dynamics, feedback and
      delay.
AB  - This paper offers dose-response-time data analysis of four different case studies
      where the pharmacological response (neuronal ACh-release, tail-flick response,
      locomotor activity, NEFA) was modelled by a biophase-driven turnover model. The
      analysis uses a mathematical/analytical perspective in which analytic properties
      of the models involved are exploited in order to address the dual challenge of
      extracting information from these time-series about (i) the biophase kinetics
      following different routes of administration and (ii) pharmacodynamic issues such
      as transduction, saturation, and adaptation, and more specifically, parameter
      identifiability, such as correct estimation of potency (SD50 or ID50). It is
      shown how many of these estimates can be obtained by analytical means, giving
      considerable insight in the dynamics involved. 

PMID- 24751676
TI  - Student-created independent learning modules: An easy high-value addition to
      radiology clerkships.
AB  - RATIONALE AND OBJECTIVES: Modern radiology clerkships require a rigorous, in
      depth curriculum usually involving a variety of educational activities. With
      increasingly constrained faculty time and departmental resources, finding
      activities that are easy to implement and of high educational value can be a
      challenge. MATERIALS AND METHODS: We introduced a novel educational activity to
      our radiology clerkship in which students created independent learning modules
      (ILMs) that were reviewed by their classmates. Feedback surveys were used to
      assess the activity and guide a revision to the program. Feedback surveys after
      the revision were used to assess the overall perceived value of the program.
      RESULTS: Twenty-seven students in two successive sessions of our elective
      radiology clerkship completed the ILM activity and provided feedback. Sixty-four
      students in five subsequent sessions completed a modified version of the activity
      and provided feedback. Students in this final group rated the activity's
      educational value at 8.3/10, with most describing both the creation and reviewing
      of the ILMs as similarly or more educationally valuable than lectures (41 of 64
      [64%], 48 of 64 [75%], respectively). Students indicated the target ILM length of
      15 minutes was "about right" (61 of 64 [95%]), and that the overall proportion of
      the course dedicated to the ILM activity was appropriate (49 of 64 [77%]).
      CONCLUSIONS: A novel student-created ILM activity was highly reviewed by
      radiology elective students, both with regard to the educational value of
      creating and taking the ILMs. Clerkship directors wishing to supplement their
      curricula with an easy-to-implement high-value activity may consider adding a
      student-created ILM assignment.

PMID- 24751677
TI  - Adrenal insufficiency as a result of long-term misuse of topical corticosteroids.
AB  - The treatment of chronic inflammatory skin disease is associated with the use of
      topical corticosteroids. Their efficacy, tolerability and adverse effects depend
      on several factors, specifically potency, type of preparation, extemporaneous
      dilutions, quantity used, magnitude of the treated body surface, frequency of
      application, location, patient age, method of application and condition of the
      skin barrier. We report on two men suffering from chronic inflammatory skin
      disease, who presented with fatigue and cushingoid appearance after prolonged
      self-application of potent corticosteroids. Impairment of the skin barrier due to
      their underlying skin disease, frequent self-application of topical steroids and
      repeated application of the entire body led to extensive absorption of these
      substances, eventually culminating in the suppression of the pituitary
      hypothalamic-adrenal axis. In conclusion, topical corticosteroids are effective
      and well-established therapeutic modalities. However, inappropriate use of
      topical corticosteroids can cause side effects.

PMID- 24751680
TI  - Combined flexor carpi radialis tear and flexor carpi radialis brevis tendinopathy
      identified by ultrasound: a case report.
AB  - A 63-year-old right-handed office worker presented with acute right wrist pain
      after lifting a heavy file at work. Results of a clinical examination suggested
      flexor carpi radialis tendinopathy. Diagnostic ultrasound (US) not only detected
      a complete flexor carpi radialis tear but also revealed the presence of a
      concomitant flexor carpi radialis brevis (FCRB) tendon with associated
      tenosynovitis. The ability of US to correctly identify the FCRB has not been
      previously reported. Furthermore, the US appearance of FCRB tendinopathy and
      tenosynovitis has not been described. High-resolution US can identify the FCRB
      muscle-tendon in the wrist region. Sonologists and sonographers should be aware
      of the US appearance of the FCRB as well as the potential for the FCRB to
      contribute to radial wrist pain syndromes. 

PMID- 24751678
TI  - RCAN1 overexpression exacerbates calcium overloading-induced neuronal apoptosis.
AB  - Down Syndrome (DS) patients develop characteristic Alzheimer's Disease (AD)
      neuropathology after their middle age. Prominent neuronal loss has been observed
      in the cortical regions of AD brains. However, the underlying mechanism leading
      to this neuronal loss in both DS and AD remains to be elucidated. Calcium
      overloading and oxidative stress have been implicated in AD pathogenesis. Two
      major isoforms of regulator of calcineurin 1 (RCAN1), RCAN1.1 and RCAN1.4, are
      detected in human brains. In this report we defined the transcriptional
      regulation of RCAN1.1 and RCAN1.4 by two alternative promoters. Calcium
      overloading upregulated RCAN1.4 expression by activating RCAN1.4 promoter through
      calcineurin-NFAT signaling pathway, thus forming a negative feedback loop in
      isoform 4 regulation. Furthermore, RCAN1.4 overexpression exacerbated calcium
      overloading-induced neuronal apoptosis, which was mediated by caspase-3 apoptotic
      pathway. Our results suggest that downregulating RCAN1.4 expression in neurons
      could be beneficial to AD patients. 

PMID- 24751681
TI  - Association study on ADAM33 polymorphisms in mite-sensitized persistent allergic
      rhinitis in a Chinese population.
AB  - BACKGROUND: The ADAM33 gene has been identified as a potentially important asthma
      candidate gene and polymorphisms in this gene have been shown to be associated
      with asthma and seasonal allergic rhinitis. OBJECTIVE: To assess whether the
      ADAM33 polymorphisms are associated with persistent allergic rhinitis (PER) due
      to house dust mites in a Chinese population. METHODS: In a hospital-based case
      control study of 515 patients with mite-sensitized PER and 495 healthy controls,
      we genotyped seven single nucleotide polymorphisms (SNPs) in ADAM33. Serum levels
      of eosinophil cationic protein, total IgE and allergen-specific IgE against
      Dermatophagoides pteronyssinus and Dermatophagoides farinae were measured by the
      ImmunoCAP assays. RESULTS: In the single-locus analysis, three polymorphisms,
      rs3918392 (F1), rs528557 (S2) and rs2787093, were significantly associated with
      mite-sensitized PER. SNP S2 was associated with significantly increased risk both
      of asthmatic and nonasthmatic mite-sensitized PER. In the combined genotypes
      analysis, individuals with 2-4 risk alleles had a significantly higher risk of
      mite-sensitized PER (adjusted OR = 1.99, 95% CI = 1.50-2.62) than those with 0-1
      risk alleles. Haplotype-based association analysis revealed that the ACAGCCT
      haplotype might have potential to protect against mite-sensitized PER (adjusted
      OR = 0.67; 95% CI = 0.49-0.90). CONCLUSIONS: Polymorphisms in the ADAM33 gene may
      contribute to susceptibility of mite-sensitized PER in this Chinese population.

PMID- 24751682
TI  - Utilization of magnetic-activated cell sorting and high-density single nucleotide
      polymorphism microarrays improves diagnostic yield and prognostic value in
      clinical testing for patients with multiple myeloma and normal routine chromosome
      study.

PMID- 24751684
TI  - Protective effects of blueberries (Vaccinium corymbosum L.) extract against
      cadmium-induced hepatotoxicity in mice.
AB  - The oxidative status and morphological changes of mouse liver exposed to cadmium
      chloride (Cd(II)) and therapeutic potential of blueberry (Vaccinium corymbosum
      L.) extract against Cd(II)-induced hepatic injury were investigated. A variety of
      parameters were evaluated, including lipid peroxidation (LPO), protein carbonyl
      (PCO) level, DNA fragment, as well as antioxidative defense system (i.e.,
      superoxide dismutase (SOD), catalase (CAT), reduced glutathione (GSH)). Elemental
      analysis and evaluation of morphological changes and NO levels were also
      performed. Exposure to Cd(II) led to increased LPO and PCO as well as DNA
      fragment and a reduction of SOD and CAT activities, however, the content of GSH
      elevated probably due to biological adaptive-response. In contrast, co-treatment
      of anthocyanin (Ay) inhibited the increased oxidative parameters as well as
      restored the activities of antioxidative defense system in a dose-dependent
      manner. Ay administration regained these morphological changes caused by
      intoxication of Cd(II) to nearly normal levels. Moreover, the accumulation of
      Cd(II) in liver may be one of the reasons for Cd(II) toxicity and Ay can chelate
      with Cd(II) to reduce Cd(II) burden. The influence of Cd(II) on the Zn and Ca
      levels can also be adjusted by the co-administration of Ay. Exposure to Cd(II)
      led to an increase of NO and Ay reduced NO contents probably by directly
      scavenging. Potential mechanisms for the protective effect of Ay have been
      proposed, including its anti-oxidative and anti-inflammatory effect along with
      the metal-chelating capacity. These results suggest that blueberry extract may be
      valuable as a therapeutic agent in combating Cd(II)-induced tissue injury. 

PMID- 24751683
TI  - A genetic variant in primary miR-378 is associated with risk and prognosis of
      hepatocellular carcinoma in a Chinese population.
AB  - BACKGROUND: MiR-378 has been reported to be related to cell survival, tumor
      growth and angiogenesis and may participate in hepatocellular carcinoma (HCC)
      development and prognosis. Genetic variants in primary miR-378 (pri-miR-378) may
      impact miR-378 expression and contribute to HCC risk and survival. This study
      aimed to assess the associations between a genetic variant in primary miR-378 and
      HCC susceptibility and prognosis. METHODS: We conducted a case-control study to
      analyze the association of rs1076064 in pri-miR-378 with hepatocellular carcinoma
      risk in 1300 HCC patients with positive hepatitis B virus (HBV) and 1344 HBV
      carriers. Then, we evaluated the correlation between the polymorphism and
      hepatocellular carcinoma prognosis in 331 HCC patients at either intermediate or
      advanced stage without surgical treatment. RESULTS: The variant genotypes of
      rs1076064 were associated with a decreased HCC risk in HBV carriers [Adjusted
      odds ratio (OR) = 0.90, 95% confidence intervals (CI) = 0.81-1.00, P = 0.047].
      Moreover, HCC patients with the variant genotypes were associated with a better
      survival [Adjusted hazard ratio (HR) = 0.70, 95% CIs = 0.59-0.83, P<0.0001 in an
      additive genetic model]. The reporter gene assay showed that the variant G allele
      of rs1076064 exerted higher promoter activity than the A allele. CONCLUSIONS:
      These findings indicate that rs1076064 may be a biomarker for HCC susceptibility
      and prognosis through altering pri-miR-378 transcription.

PMID- 24751685
TI  - Age-related differences in kidney injury biomarkers induced by cisplatin.
AB  - Acute kidney injury (AKI) occurs in a half of cisplatin (CDDP)-treated patients.
      Traditional biomarkers including blood urea nitrogen (BUN) and serum creatinine
      (SCr) are still used for detection of CDDP-induced AKI, but these biomarkers are
      not specific or sensitive. The aim of this study was to identify the specific and
      sensitive biomarkers against CDDP-induced renal injury between young (3-week-old)
      and old (20-week-old) rats. All animals were intraperitoneally injected once with
      CDDP (6 mg/kg). After 3 days, all animals were sacrificed and serum, urine, and
      kidney tissues were collected. Urinary and serum biomarkers as well as
      histological changes were measured. CDDP-induced proximal tubular damage was
      apparent from histopathological examination, being more severe in 3-week-old rats
      accompanied by increased number of TUNEL-positive apoptotic cells. This was
      associated with elevated urinary kidney injury molecule-1 (KIM-1), glutathione-S
      transferase alpha (GST-alpha), vascular endothelial growth factor (VEGF), and
      tissue inhibitor of metalloproteinases-1 (TIMP-1). In contrast, the levels of
      neutrophil gelatinase-associated lipocalin (NGAL) and osteopontin were
      significantly increased in 20-week-old rats after CDDP treatment. These results
      indicate that the use of age-specific urinary biomarkers is necessary to
      diagnosis of CDDP-induced AKI. Especially, urinary KIM-1, GST-alpha, TIMP-1, and
      VEGF levels may help in the early diagnosis of young patients with CDDP-induced
      AKI.

PMID- 24751686
TI  - Importance of Bnp changes during the follow-up in elderly outpatients with heart
      failure.
AB  - BACKGROUND: The aim of the present study was to analyze whether absolute BNP and
      relative BNP change values during follow-up of elderly patients with chronic HF
      could predict the development of acute decompensated episodes. METHODS AND
      RESULTS: A total population of 108 elderly outpatients with the diagnosis of HF
      was retrospectively reviewed. Available BNP levels after at least one stable
      visit and one acute decompensated episode were required. Follow-up period was 12
      months (343 visits, 42.6% decompensated HF episodes). Relative BNP changes were
      analyzed: "CC period" (patients who remained stable) and "CD period" (patient who
      suffered from a decompensated HF episode). Changes in BNP levels were
      significantly higher in CD than in CC periods (mean and median differences 138%
      and 85%, vs 16% and 0%, respectively; p<0.001). The clinical model (AUC=0.83) had
      a sensitivity of 67.06%, and a specificity of 80.36%. Relative BNP change (29%)
      showed by itself, a similar AUC (0.83) and specificity (79%) and an improved
      sensitivity (0.80) than the clinical model. When relative BNP change was
      introduced at the clinical model, a similar specificity was obtained and the
      diagnostic accuracy, AUC (0.89 vs 0.83, p=0.01) and sensitivity were improved.
      Absolute BNP changes showed worse AUC than that derived from relative BNP changes
      or clinical assessment. CONCLUSIONS: Percent BNP change values during the follow
      up showed better results than absolute BNP values and improved the clinical
      assessment for diagnostic of decompensated HF episodes in elderly outpatients.

PMID- 24751687
TI  - Tumor necrosis factor-alpha 308G>A polymorphism and risk of rheumatic heart
      disease: a meta-analysis.
AB  - Rheumatic heart disease (RHD) remains a serious cardiovascular disorder across
      the world. Tumor necrosis factor alpha (TNF-alpha) codifies a potent
      immunomodulator and pro-inflammatory cytokine that mediates diverse pathological
      processes. A promoter 308G>A polymorphism in TNF-alpha has been implicated in RHD
      risk. However, the results remain controversial. Therefore, to evaluate more
      precise estimations of the relationship, a meta-analysis was performed. A total
      of 7 studies including 735 RHD cases and 926 controls were involved in this meta
      analysis. Overall, our results revealed that there was a significant association
      with RHD risk in three genetic models (homozygous model: OR = 3.06, 95%CI = 1.22
      10.60, P = 0.020; dominant model, OR = 2.03, 95%CI = 1.01-4.07, P = 0.048; and
      recessive model, OR = 4.26, 95%CI = 2.41-7.55, P < 0.001). Further ethnic
      population analysis found a significantly increased risk of RHD among Asians and
      Europeans. Interestingly, similar results were found among hospital-based
      studies. Begg's funnel plot and Egger's test did not reveal any publication bias.
      Taken together, this meta-analysis demonstrates that the TNF-alpha 308G>A
      polymorphism is associated with RHD susceptibility, and it contributes to the
      increased risk of RHD. However, additional well-designed studies with larger
      samples are warranted to confirm these findings. 

PMID- 24751688
TI  - Simple genetics language as source of miscommunication between genetics
      researchers and potential research participants in informed consent documents.
AB  - Informed consent is based on communication, requiring language to convey meanings
      and ensure understandings. The purpose of this study was to investigate the use
      of language in informed consent documents used in the genetics research funded by
      Canadian Institutes of Health Research and Genome Canada. Consent documents were
      requested from the principal investigators in a recent round of funding. A
      qualitative content analysis was performed, supported by NVivo7TM. Potential
      barriers to informed consent were identified, including language that was vague
      and variable, words with both technical and common meanings, novel phrases
      without clear meaning, a lack of definitions, and common concepts that assume new
      definitions in genetics research. However, we noted that difficulties in
      comprehension were often obscured because the words used were generally simple
      and familiar. We conclude that language gaps between researcher and potential
      research participants may unintentionally impair comprehension and ultimately
      impair informed consent in genomics research. 

PMID- 24751689
TI  - Thai visitors' expectations and experiences of explainer interaction within a
      science museum context.
AB  - In Western literature, there is evidence that museum explainers offer significant
      potential for enhancing visitors' learning through influencing their knowledge,
      content, action, behaviour and attitudes. However, little research has focused on
      the role of explainers in other cultural contexts. This study explored
      interactions between visitors and museum explainers within the setting of
      Thailand. Two questionnaires were distributed to 600 visitors and 41 museum
      explainers. The results demonstrated both potential similarities and differences
      with Western contexts. Explainers appeared to prefer didactic approaches,
      focussing on factual knowledge rather than encouraging deep learning. Two-way
      communication, however, appeared to be enhanced by the use of a 'pseudo-sibling
      relationship' by explainers. Traditional Thai social reserve was reduced through
      such approaches, with visitors taking on active learning roles. These findings
      have implications for training museum explainers in non-Western cultures, as well
      as museum communication practice more generally. 

PMID- 24751691
TI  - A spotlight on preschool: the influence of family factors on children's early
      literacy skills.
AB  - RATIONALE: Phonological awareness, letter knowledge, oral language (including
      sentence recall) and rapid automatised naming are acknowledged within-child
      predictors of literacy development. Separate research has identified family
      factors including socio-economic status, parents' level of education and family
      history. However, both approaches have left unexplained significant amounts of
      variance in literacy outcomes. This longitudinal study sought to improve
      prospective classification accuracy for young children at risk of literacy
      failure by adding two new family measures (parents' phonological awareness and
      parents' perceived self-efficacy), and then combining the within-child and family
      factors. METHOD: Pre-literacy skills were measured in 102 four year olds (46
      girls and 56 boys) at the beginning of Preschool, and then at the beginning and
      end of Kindergarten, when rapid automatised naming was also measured. Family
      factors data were collected at the beginning of Preschool, and children's
      literacy outcomes were measured at the end of Year 1 (age 6-7 years). RESULTS:
      Children from high-risk backgrounds showed poorer literacy outcomes than low-risk
      students, though three family factors (school socio-economic status, parents'
      phonological awareness, and family history) typically accounted for less Year 1
      variance than the within-child factors. Combining these family factors with the
      end of Kindergarten within-child factors provided the most accurate
      classification (i.e., sensitivity = .85; specificity = .90; overall correct =
      .88). IMPLICATIONS: Our approach would identify at-risk children for intervention
      before they began to fail. Moreover, it would be cost-effective because although
      few at-risk children would be missed, allocation of unnecessary educational
      resources would be minimised.

PMID- 24751693
TI  - SUMOylation and deimination of proteins: two epigenetic modifications involved in
      Giardia encystation.
AB  - SUMOylation, a posttranslational modification of proteins, has been recently
      described as vital in eukaryotic cells. In a previous work, we analyzed the role
      of SUMO protein and the genes encoding the putative enzymes of the SUMOylation
      pathway in the parasite Giardia lamblia. Although we observed several SUMOylated
      proteins, only the enzyme Arginine Deiminase (ADI) was confirmed as a SUMOylated
      substrate. ADI is involved in the survival of the parasite and, besides its role
      in ATP production, it also catalyzes the modification of arginine residues to
      citrulline in the cytoplasmic tail of surface proteins. During encystation,
      however, ADI translocates to the nuclei and downregulates the expression of the
      Cyst Wall Protein 2 (CWP2). In this work, we made site-specific mutation of the
      ADI SUMOylation site (Lys101) and observed that transgenic trophozoites did not
      translocate to the nuclei at the first steps of encystation but shuttled in the
      nuclei late during this process through classic nuclear localization signals.
      Inside the nuclei, ADI acts as a peptidyl arginine deiminase, being probably
      involved in the downregulation of CWPs expression and cyst wall formation. Our
      results strongly indicate that ADI plays a regulatory role during encystation in
      which posttranslational modifications of proteins are key players. 

PMID- 24751694
TI  - Primary cutaneous meningioma combined with dermal melanocytosis and vascular
      malformation.

PMID- 24751695
TI  - Orbital resolution of molecules covalently attached to a clean semiconductor
      surface.
AB  - Understanding the chemical and electronic nature of molecules attached to
      semiconductors is of great importance in the study of molecule-based electronic
      devices. Resolving individual molecular orbitals using scanning tunnelling
      microscopy is a straightforward approach but remains challenging on the
      semiconductor surfaces because of their highly reactive dangling bonds. Here we
      show that hybridized molecular orbitals of pyridazine molecules covalently
      attached to Ge(100) surfaces can be resolved by scanning tunnelling microscopy.
      Pyridazine binds to Ge(100) through single/double dative bond(s) and presents two
      types of features with three and four lobes. These features resemble the lowest
      unoccupied molecular orbitals of free pyridazine, which are hybridized by the
      surface states in the adsorbed state. The adsorbing sites, binding mechanisms,
      orientations and electronic properties of the adsorbed molecules are convincingly
      determined. Our results indicate that orbital resolution of molecules covalently
      attached to semiconductors is accessible despite of their high reactivity. 

PMID- 24751692
TI  - Inhibition of endogenous MTF-1 signaling in zebrafish embryos identifies novel
      roles for MTF-1 in development.
AB  - The metal responsive element-binding transcription factor-1 (MTF-1) responds to
      changes in cellular zinc levels caused by zinc exposure or disruption of
      endogenous zinc homeostasis by heavy metals or oxygen-related stress. Here we
      report the functional characterization of a complete zebrafish MTF-1 in
      comparison with the previously identified isoform lacking the highly conserved
      cysteine-rich motif (Cys-X-Cys-Cys-X-Cys) found in all other vertebrate MTF-1
      orthologs. In an effort to develop novel molecular tools, a constitutively
      nuclear dominant-negative MTF-1 (dnMTF-1) was generated as tool for inhibiting
      endogenous MTF-1 signaling. The in vivo efficacy of the dnMTF-1 was determined by
      microinjecting in vitro transcribed dnMTF-1 mRNA into zebrafish embryos (1-2 cell
      stage) followed by transcriptomic profiling using an Agilent 4x44K array on 28-
      and 36-hpf embryos. A total of 594 and 560 probes were identified as
      differentially expressed at 28hpf and 36hpf, respectively, with interesting
      overlaps between timepoints. The main categories of genes affected by the
      inhibition of MTF-1 signaling were: nuclear receptors and genes involved in
      stress signaling, neurogenesis, muscle development and contraction, eye
      development, and metal homeostasis, including novel observations in iron and heme
      homeostasis. Finally, we investigate both the transcriptional activator and
      transcriptional repressor role of MTF-1 in potential novel target genes
      identified by transcriptomic profiling during early zebrafish development. 

PMID- 24751696
TI  - Epidemiology of tuberculosis cases with end-stage renal disease, California,
      2010.
AB  - BACKGROUND/AIMS: Few studies have compared population-based tuberculosis (TB)
      incidence rates by end-stage renal disease (ESRD) status. No studies have
      compared TB genotypes by ESRD status to determine whether TB disease resulted
      from recent transmission or reactivation of latent TB infection (LTBI). We
      calculated TB incidence rates and compared demographic and clinical
      characteristics and genotypes among TB cases by ESRD status. METHODS: This
      analysis was based on prospective surveillance for TB cases during 2010 in
      California. Clustered genotype was defined as >=2 culture-positive TB cases with
      matching genotypes in the same county. The chi(2) or Wilcoxon rank-sum test was
      used to compare variables. RESULTS: During 2010, 83 TB cases with ESRD and 2,244
      cases without ESRD were reported in California; TB incidence rates were
      110.3/100,000 and 6.0/100,000, respectively. ESRD case patients versus patients
      without ESRD were more likely to be older (median age 66 vs. 49 years; p <
      0.001), foreign-born persons who had arrived in the USA >5 years before TB
      diagnosis (97 vs. 75%; p < 0.001) and dead at TB diagnosis (7 vs. 2%; p = 0.01).
      ESRD patients were less likely to have a positive tuberculin skin test (50 vs.
      80%; p < 0.001), positive acid-fast bacilli sputum smears (33 vs. 53%; p = 0.01)
      and cavities on chest radiography (6 vs. 21%; p = 0.01). No differences in
      proportions of clustered TB genotypes were detected (20 vs. 23%; p = 0.54).
      CONCLUSIONS: Rates of TB are 18 times higher in California's ESRD population, and
      TB disease likely occurred due to LTBI reactivation because few patients had
      clustered genotypes. Efforts to prevent TB among ESRD patients may require the
      use of newer diagnostic tests and promotion of LTBI treatment.

PMID- 24751697
TI  - Characterization of a novel single-chain bispecific antibody for retargeting of T
      cells to tumor cells via the TCR co-receptor CD8.
AB  - There is currently growing interest in retargeting of effector T cells to tumor
      cells via bispecific antibodies (bsAbs). Usually, bsAbs are directed on the one
      hand to the CD3 complex of T cells and on the other hand to a molecule expressed
      on the surface of the target cell. A bsAb-mediated cross-linkage via CD3 leads to
      an activation of CD8+ T cells and consequently to killing of the target cells. In
      parallel, CD4+ T cells including TH1, TH2, TH17 cells and even regulatory T cells
      (Tregs) will be activated as well. Cytokines produced by CD4+ T cells can
      contribute to severe side effects e. g. life-threatening cytokine storms and,
      thinking of the immunosupressive function of Tregs, can even be
      counterproductive. Therefore, we asked whether or not it is feasible to limit
      retargeting to CD8+ T cells e. g. via targeting of the co-receptor CD8 instead of
      CD3. In order to test for proof of concept, a novel bsAb with specificity for CD8
      and a tumor-associated surface antigen was constructed. Interestingly, we found
      that pre-activated (but not freshly isolated) CD8+ T cells can be retargeted via
      CD8-engaging bsAbs leading to an efficient lysis of target cells. 

PMID- 24751698
TI  - Premature immunosenescence is associated with memory dysfunction in rheumatoid
      arthritis.
AB  - BACKGROUND: Rheumatoid arthritis (RA) has been associated with premature
      immunosenescence and an increased prevalence of age-related morbidities including
      poor cognitive function. OBJECTIVE: We explored the relationships among
      lymphocyte subsets and memory in RA. METHODS: Thirty patients with RA and 19 age
      matched healthy controls took part in this study. Cognitive function stress and
      depression scores were evaluated by structured clinical questionnaires.
      Lymphocytes were isolated and immunophenotyped by flow cytometry to investigate
      the following subsets: B cells, activated and naive/memory T cells, regulatory
      FoxP3+ T (Treg) cells, Th17+ cells, NK cells and senescence-associated CD28- T
      cells. RESULTS: RA patients were more depressed than controls, but stress levels
      were similar in the 2 groups. Patients had impaired memory performance compared
      to controls, demonstrated by lower Mini-Mental State Examination scores and
      logical and working memories (all p < 0.0001). These group effects remained
      significant after correcting for depression and age. Patients had expansion of
      regulatory T cells, naive CD4+ T cells and CD8+CD28- cells but reduced
      percentages of B cells and memory CD8+CD45RO+ T cells compared to controls.
      CD8+CD28- and CD8+CD45RO+ T cells were found to be negatively associated with
      memory. CONCLUSION: RA patients had reduced memory performance compared to
      healthy controls. Expansion of activated and senescence-associated T cells was
      correlated with poor memory performance.

PMID- 24751699
TI  - Gram negative wound infection in hospitalised adult burn patients--systematic
      review and metanalysis-.
AB  - BACKGROUND: Gram negative infection is a major determinant of morbidity and
      survival. Traditional teaching suggests that burn wound infections in different
      centres are caused by differing sets of causative organisms. This study
      established whether Gram-negative burn wound isolates associated to clinical
      wound infection differ between burn centres. METHODS: Studies investigating adult
      hospitalised patients (2000-2010) were critically appraised and qualified to a
      levels of evidence hierarchy. The contribution of bacterial pathogen type, and
      burn centre to the variance in standardised incidence of Gram-negative burn wound
      infection was analysed using two-way analysis of variance. PRIMARY FINDINGS:
      Pseudomonas aeruginosa, Klebsiella pneumoniae, Acinetobacter baumanni,
      Enterobacter spp., Proteus spp. and Escherichia coli emerged as the commonest
      Gram-negative burn wound pathogens. Individual pathogens' incidence did not
      differ significantly between burn centres (F (4, 20) = 1.1, p = 0.3797; r2 =
      9.84). INTERPRETATION: Gram-negative infections predominate in burn surgery. This
      study is the first to establish that burn wound infections do not differ
      significantly between burn centres. It is the first study to report the pathogens
      responsible for the majority of Gram-negative infections in these patients.
      Whilst burn wound infection is not exclusive to these bacteria, it is hoped that
      reporting the presence of this group of common Gram-negative "target organisms"
      facilitate clinical practice and target research towards a defined clinical
      demand.

PMID- 24751700
TI  - Long-term follow-up using 18F-FDG PET/CT for postoperative olfactory
      neuroblastoma.
AB  - PURPOSE: The present study evaluated the usefulness of postoperative fluorine-18
      fluorodeoxyglucose (F-FDG) PET/computed tomography (CT) in the management of
      olfactory neuroblastoma (ONB). MATERIALS AND METHODS: Ten patients (eight men and
      two women; mean age, 48.5 years) with histologically confirmed ONB who underwent
      craniofacial resection were retrospectively included in this study. A total of 42
      whole-body F-FDG PET/CT scans for postoperative surveillance or restaging were
      reviewed. The mean time from operation until the PET/CT scan was 42.1 months. We
      evaluated the F-FDG uptake and the presence of recurrent lesions during the
      follow-up period and compared the PET/CT results with the results of MRI and
      clinical examination (endoscopy). RESULTS: Seven of the 10 patients had 24
      recurrent lesions, and 18 of these recurrent lesions (seven local recurrences,
      eight cervical lymph node metastases, one intracranial metastasis, and two
      distant metastases) were F-FDG positive (75.0%). Three local recurrences and
      three intracranial metastases were false negative and were detected by endoscopy
      and MRI, respectively. The mean time from operation until recurrence was 51.4
      months, and 17 lesions (70.8%) occurred more than 2 years after the initial
      operation. CONCLUSION: Although F-FDG PET/CT is useful for the detection of
      postoperative recurrences of ONB, long-term follow-up combined with endoscopy and
      MRI is mandatory.

PMID- 24751701
TI  - Incremental value of 18F-FDG PET/CT in therapeutic decision-making of potentially
      curable esophageal adenocarcinoma.
AB  - AIMS AND OBJECTIVES: The aim of the study was to estimate the incremental value
      of fluorine-18 fluorodeoxyglucose (F-FDG) PET/computed tomography (CT) in aiding
      treatment decisions in a specific cohort of patients with lower esophageal and
      gastroesophageal junction adenocarcinoma who were considered for potentially
      curative treatment on the basis of conventional imaging. MATERIALS AND METHODS:
      The study included patients referred for a staging F-FDG PET/CT who were
      considered for potentially curative treatment (neoadjuvant therapy followed by
      surgery or definitive chemoradiotherapy) by a multidisciplinary tumor board. The
      proportion of patients with M1b disease (American Joint Committee on Cancer, 6th
      ed.) detected on F-FDG PET/CT was calculated. The sensitivity, specificity,
      positive and negative predictive values, and accuracy of F-FDG PET/CT for M1b
      disease were calculated. PET/CT findings were verified with histopathological
      analysis; when it was not possible to obtain pathological confirmation,
      correlative imaging or follow-up imaging studies were used for validation.
      RESULTS: A total of 156 patients who fulfilled the inclusion criteria were
      analyzed. F-FDG PET/CT detected M1b disease in 25 patients (16%), changing the
      intent of treatment from potentially curative to palliative. In five patients,
      PET/CT failed to detect distant metastases. The sensitivity, specificity,
      positive predictive value, negative predictive value, and accuracy of F-FDG
      PET/CT for detecting M1b disease were 83.3, 98.4, 92.5, 96.1, and 95.3%,
      respectively. Additional surgical procedures (hemicolectomy and polypectomy) were
      performed in three patients because of the detection of a second primary cancer
      in the colon in two patients and a colonic dysplastic polyp in one patient.
      CONCLUSION: In patients who are considered to be potentially curable after
      conventional imaging, F-FDG PET/CT can detect unsuspected sites of distant
      metastases (M1b) in a significant number of cases and thus contribute to the
      clinical decision-making process. PET/CT should be an integral part of the
      staging workup of patients with esophageal adenocarcinoma.

PMID- 24751702
TI  - Adverse effects of radioactive iodine-131 treatment for differentiated thyroid
      carcinoma.
AB  - Use of radioactive iodine is an essential adjuvant treatment strategy after
      thyroidectomy in patients with differentiated thyroid carcinoma. Although
      generally safe, radioiodine therapy has some potential side effects, classified
      as early and late complications, which we have reviewed in this paper. Early
      complications include gastrointestinal symptoms, radiation thyroiditis,
      sialadenitis/xerostomia, bone marrow suppression, gonadal damage, dry eye, and
      nasolacrimal duct obstruction. The late complications include secondary cancers,
      pulmonary fibrosis, permanent bone marrow suppression, and genetic effects. As I
      is an efficacious form of treatment that can significantly decrease the rate of
      mortality, recurrence, and metastasis, and as the side effects are often minor
      and well tolerated, radioiodine therapy remains the principal mode of treatment
      for patients with differentiated thyroid carcinoma. 

PMID- 24751703
TI  - A comparison between upright and supine myocardial perfusion imaging with
      attenuation correction.
AB  - OBJECTIVE: The Digirad Cardius XACT is an upright myocardial perfusion imaging
      (MPI) single photon emission computed tomography system offering low-dose
      computed tomography for attenuation correction (AC). This study compares patient
      acceptability and image appearance for both non-AC and AC images on the XACT with
      supine MPI performed on a GE Infinia Hawkeye. PATIENTS AND METHODS: A total of 47
      patients [29 male patients; mean (range) BMI, 29.1 (21.0-57.5) kg/m] referred for
      routine MPI underwent rest and stress MPI on the XACT and Infinia. Non-AC and AC
      bullseye plots were created and uptake scores were recorded in each of five
      segments. All studies were reported by an experienced observer with clinical
      details available. A patient questionnaire was used to determine the relative
      comfort with the two systems. RESULTS: Perfusion patterns on upright and supine
      non-AC images were significantly different and displayed a notable distinction
      between sexes. Perfusion patterns on upright and supine AC images were similar
      for both male and female patients, although some discrepancies between diagnostic
      reports still existed. A strong preference for upright imaging was demonstrated
      by the patient questionnaire. CONCLUSION: Changes in soft-tissue and
      diaphragmatic attenuation between upright and supine MPI can be overcome with the
      addition of AC. However, clinicians should still ensure that they are aware of
      typical artefacts produced by upright and supine imaging.

PMID- 24751704
TI  - 99mTc-Methylene diphosphonate SPECT/CT as the one-stop imaging modality for the
      diagnosis of osteoid osteoma.
AB  - PURPOSE: The aim of this study was to evaluate the utility of Tc-methylene
      diphosphonate (Tc-MDP) single-photon emission tomography (SPECT)/computed
      tomography (CT) for the diagnosis of osteoid osteoma and compare the same with
      three-phase planar bone scintigraphy (BS) and CT alone. MATERIALS AND METHODS:
      Data of 31 patients (age: 20.6+/-13.2 years; male: 80.6%) who had undergone Tc
      MDP BS with SPECT/CT for clinically and/or radiographically suspected osteoid
      osteoma were retrospectively evaluated. Planar BS images were analyzed by an
      experienced nuclear medicine physician. CT images were evaluated by an
      experienced radiologist. SPECT/CT images were evaluated by the nuclear medicine
      physician and radiologist in consensus. On the basis of the diagnostic confidence
      the interpreters used a scoring scale of 1-3, in which 1 is negative for osteoid
      osteoma, 2 is equivocal, and 3 is positive for osteoid osteoma. For the
      calculation of sensitivity, specificity, and predictive values for planar BS, CT,
      and SPECT/CT an interpretive score of 2 or higher was taken as positive for
      osteoid osteoma. Receiver operating characteristic curve analysis was performed
      and the area under the curve was calculated and compared. Histopathology and
      microbiology/clinical imaging follow-up was used as the reference standard.
      RESULTS: There were nine equivocal lesions on planar BS and five equivocal
      lesions on CT, but none on SPECT/CT. The sensitivity, specificity, and accuracy
      of SPECT/CT were all 100%; those of CT were 77.8, 92.3, and 83.8% and those of
      planar BS were 100, 38.4, and 74.1%, respectively. On comparison, the area under
      the curve of SPECT/CT was significantly larger than that of planar BS (1.00 vs.
      0.761; P=0.005) and CT (1.00 vs. 0.872; P=0.044). However, no significant
      difference was seen between planar BS and CT (0.761 vs. 0.872; P=0.236).
      CONCLUSION: Tc-MDP SPECT/CT shows excellent diagnostic accuracy for osteoid
      osteoma and can be used as a one-stop imaging modality for the same. It is
      superior to planar BS and CT alone for the diagnosis of suspected osteoid
      osteoma.

PMID- 24751705
TI  - Reconstruction of semiautomated cardiac regions of interest using iodine-123
      metaiodobenzylguanidine myocardial scintigraphy.
AB  - INTRODUCTION: Analysis using cardiac iodine-123 metaiodobenzylguanidine (MIBG)
      scintigraphy with regions of interest (ROIs) is useful for assessing myocardial
      sympathetic activity. However, manual placement of the cardiac ROI is sometimes
      difficult because myocardial MIBG uptake is reduced in patients with heart
      failure. A new method was developed to reconstruct the semiautomated cardiac ROI
      in a sympathetic denervated heart. MATERIALS AND METHODS: Using dynamic planar
      data, a summed image was generated and the matrix size was changed. Then, the
      radial count profiles originating from the center of the left ventricle were
      generated to extract the myocardial count profiles. An asymmetric Gaussian
      distribution was fitted to each profile and the epicardial border was defined by
      the threshold method. This program was tested in 50 patients, and its
      reproducibility was validated when compared with the manual tracing method.
      RESULTS: The semiautomated method yielded a better quality image compared with
      the standard image with higher counts. Cardiac ROIs were generated successfully
      in each patient within normal limits. The intraobserver and interobserver
      agreements were excellent (P<0.0001 each). This approach showed a significantly
      higher consistency in measuring the heart-to-mediastinum ratio as compared with
      the manual tracing method (P<0.05). CONCLUSION: The semiautomated method is
      useful in generating cardiac ROIs with high reproducibility in myocardial MIBG
      imaging.

PMID- 24751706
TI  - Target weight gain during the first year of hemodialysis therapy is associated
      with patient survival.
AB  - BACKGROUND: Hemodialysis (HD) patients are exposed to a high risk of death.
      Nutritional status has been recognized as a key factor for patient survival.
      Nutritional markers have been shown to improve after HD onset. In this study we
      have analyzed the dynamics of target weight (TGW) change and the evolution of
      other nutritional parameters during the first year of HD treatment and their
      influence on patients' outcomes. METHODS: We have analyzed a retrospective cohort
      of incident patients starting HD therapy between January 2000 and January 2009,
      and studied the values and changes in TGW, interdialytic weight gain (IDWG),
      predialysis systolic blood pressure, serum albumin, protein intake, C-reactive
      protein (CRP) from the start and first week (W1), W8, W12, W26 and W52 in
      patients who survived the first year of therapy. We have analyzed the
      relationship between TGW changes with other nutritional parameters and the
      patient survival. RESULTS: Among the cohort including 363 patients starting HD
      therapy, 251 (age 65.8 +/- 14.8 years, 93 female/158 male, diabetes 36%) survived
      at least 1 year after dialysis onset and were followed for 44.9 months. During
      the first 8 weeks, the TGW decreased by 6.5 +/- 5.6% (initial TGW change). The
      initial TGW change was correlated with IDWG at W12 and W26, and with changes in
      serum albumin and nPNA (normalized protein equivalent of nitrogen appearance)
      between HD W1 and W52 (respectively +7.8 and +11.4%). From W8 to W52, the TGW
      increased by +1.9 +/- 7.4% (secondary TGW change). The Kaplan-Meier analysis
      displayed a significantly better survival in patients above the median (+2.3%) of
      the secondary TGW change (respectively -3.6 +/- 5.2% and +7.6 +/- 4.5%). The two
      groups above and below this median were not different according to age, diabetes
      or cardiovascular event history but the patients above the median had a
      significant higher IDWG and protein intake. In the Cox model analysis the patient
      overall mortality was related to age (p < 0.0001), to the secondary TGW change (p
      = 0.0001), and to the CRP level at W52 (p < 0.0001). CONCLUSIONS: The initial
      fluid removal was related to nutritional markers. The secondary TGW change during
      the first year of HD treatment calculated after the initial phase of fluid
      removal was identified as a strong predictor of survival. It was associated with
      a better food intake whereas the patient case mix was not different. These data
      highlight the importance of nutrition and food intake in the first year of
      dialysis therapy and the need for nutritional follow-up and support in incident
      HD patients. It stresses the need in understanding the key factors associated
      with food intake in this setting.

PMID- 24751707
TI  - The intracrinology of breast cancer.
AB  - The importance of intracrinology, or in situ production of steroids from
      circulating precursors, in breast cancer has been firmly established in estrogen
      actions on postmenopausal patients. Expression levels of various steroid
      synthesizing and/or metabolizing enzymes have been examined in human breast
      cancer tissues by a number of groups. The enzymes examined include those capable
      of converting circulating DHEA-S to sex steroids (STS and 3betaHSDDelta4-5
      isomerase), the group of enzymes that modulate the strength of both androgens and
      estrogens (17betaHSD family) as well as the androgenic 5alphaR enzymes and the
      estrogenic aromatase enzyme. In addition to these DHEA-related metabolism
      pathways, other intracrine pathways involving progesterone and cholesterol have
      also been examined. Some risk factors of breast cancer development, including
      obesity, have also been postulated to interact with steroid metabolising
      pathways. In this review, we aimed to summarise the current state of knowledge
      regarding intracrine metabolism including expression levels of various enzymes
      and receptors, focusing particularly upon the importance of the production of
      biologically potent steroids from circulating sulfated precursors such as DHEA-S.
      In addition, we attempted to summarise the factors, both steroidal and non
      steroidal, involved in the regulation of these enzymes and propose future
      directions for research in this particular field. The concept of intracrinology
      was first proposed over 20 years ago but there still remain many unanswered
      questions which could open new horizons for the understanding of intracrine
      metabolism in the breast. This article is part of a Special Issue entitled
      'Essential role of DHEA'. 

PMID- 24751708
TI  - Melatonin counteracts BMP-6 regulation of steroidogenesis by rat granulosa cells.
AB  - The ovarian bone morphogenetic protein (BMP) system is a physiological inhibitor
      of luteinization in growing ovarian follicles. BMP-6, which is expressed in
      oocytes and granulosa cells of healthy follicles, specifically inhibits FSH
      actions by suppressing adenylate cyclase activity. In the present study, we
      studied the role of melatonin in ovarian steroidogenesis using rat primary
      granulosa cells of immature female rat ovaries by focusing on the interaction
      with BMP-6 activity. Treatment with melatonin had no direct effect on FSH-induced
      progesterone or estradiol production by granulosa cells, and the results were not
      affected by the presence of co-cultured oocytes. In addition, synthesis of cAMP
      by granulosa cells was not significantly altered by melatonin treatment. To
      elucidate the interaction between activities of melatonin and BMPs, the effect of
      melatonin treatment on suppression of progesterone synthesis by BMP-6 was
      investigated. Interestingly, the inhibitory effect of BMP-6 on FSH-induced
      progesterone production was impaired by co-treatment with melatonin. Granulosa
      cells express higher levels of MT1 than MT2, and BMP-6 had no significant effect
      on MT1 expression in granulosa cells. However, BMP-6-induced Smad1/5/8
      phosphorylation and Id-1 transcription were suppressed by melatonin, suggesting
      that melatonin has an inhibitory effect on BMP receptor signaling in granulosa
      cells. Although the expression levels of ALK-2, -6, ActRII and BMPRII were not
      affected by melatonin, inhibitory Smad6, but not Smad7, expression was
      upregulated by melatonin. Thus, melatonin plays a role in the regulation of BMP-6
      signal intensity for controlling progesterone production in the ovary. These
      findings suggest that the effect of melatonin on maintenance of ovarian function
      is, at least in part, due to the regulation of endogenous BMP activity in
      granulosa cells. 

PMID- 24751710
TI  - Acute treatment with alcohol affects calcium signaling and contraction associated
      with apoptosis in vas deferens of periadolescent rats.
AB  - Our purpose was to verify if alcohol causes alterations on translocation of
      Ca(2+) and tension induced by KCl or noradrenaline in vas deferens of
      periadolescent Wistar rats. A single dose of alcohol (i.p. 3.0g/kg) or saline as
      control, was given 4h before sacrifice. Longitudinal strips of prostatic portion
      were mounted in vitro for simultaneous measurements of intracellular Ca(2+) and
      contractions. Fluorescence and tension were measured in strips loaded with the
      fluorescent dye fura-2. The mean values (+/-S.E.M.) of fluorescence ratios
      (F340/380) evoked by KCl were significantly lower by about 70% after alcohol, in
      relation to control. It was about 50% lower when evoked by noradrenaline. In
      relation to tension, the respective mean values (+/-S.E.M.) were lower by about
      60% in organs treated with KCl or by about 80% after noradrenaline. In some
      experiments, before noradrenaline contraction, the vas deferens was incubated
      with verapamil 10(-6)M for 30min. In these experiments, contractions by
      noradrenaline in the presence of verapamil were decreased by about 70% by
      alcohol. Alcohol decreases cytosolic calcium and contractility after KCl and
      noradrenaline, as compared with controls. In addition, alcohol promoted damage of
      lumen structures. Prostatic portion showed no striking morphometric change after
      treatment, but the number of TUNEL positive cells in muscular layer, basal lamina
      and lumen were increased by alcohol, indicating apoptosis, compared with
      controls. This investigation shows that alcohol treatment alters signaling of
      calcium which in turn compromises the contraction associated with a process of
      apoptosis of periadolescent rats. 

PMID- 24751711
TI  - Inhibitory effect of triamcinolone acetonide on synthesis of inflammatory
      mediators in the equine.
AB  - Glucocorticoids (corticosteroids) are widely used anti-inflammatory agents in
      veterinary medical practice. These drugs are considered doping agents because
      they mask pain and thus, increase injury potential in equine athletes. They
      exhibit anti-inflammatory property by binding to glucocorticoids receptor (GR) to
      control the transcription of pro- and anti-inflammatory cytokines and enzymes
      involved in the synthesis of bioactive eicosanoids. To evaluate the role of
      triamcinolone acetonide (TA) on concentrations of bioactive eicosanoids in equine
      plasma, TA (0.04 mg/kg) was intravenously administered to horses. Before (0 h)
      and after TA administration, equine whole blood (EWB) samples were collected and
      challenged with either methanol (vehicle), calcium ionophore A-23187 (CI) or
      lipopolysaccharide (LPS) to stimulate ex-vivo synthesis of eicosanoids. Plasma
      concentrations of eicosanoids were quantified using LC-MS/MRM. Results showed
      that thromboxane B2 (TXB2) was not affected by TA administration when EWB was
      stimulated with CI. However, after LPS treatment, TXB2, PGE2, PGF2alpha and 15
      (s)-HETE decreased during 2-8 h post-TA administration but recovered to
      concentrations which were not significantly different from those of pre-TA
      administration (0 h), after 24 h. When EWB was treated with CI, LTB4 was
      suppressed post-TA administration compared to 0 h. When EWB collected after TA
      administration was stimulated with LPS, LTB4 was not significantly different from
      those of 0 h. Administration of a therapeutic dose of TA (0.04 mg/kg, iv) in the
      horse suppressed biosynthesis of bioactive eicosanoids indicating the anti
      inflammatory role of TA in the horse.

PMID- 24751709
TI  - Cannabinoid and lipid-mediated vasorelaxation in retinal microvasculature.
AB  - The endocannabinoid system plays a role in regulation of vasoactivity in the
      peripheral vasculature; however, little is known about its role in regulation of
      the CNS microvasculature. This study investigated the pharmacology of
      cannabinoids and cannabimimetic lipids in the retinal microvasculature, a CNS
      vascular bed that is autoregulated. Vessel diameter (edge detector) and calcium
      transients (fura-2) were recorded from segments of retinal microvasculature
      isolated from adult, male Fischer 344 rats. Results showed that abnormal
      cannabidiol (Abn-CBD), an agonist at the putative endothelial cannabinoid
      receptor, CBe, inhibited endothelin 1 (ET-1) induced vasoconstriction in retinal
      arterioles. These actions of Abn-CBD were independent of CB1/CB2 receptors and
      were not mediated by agonists for GPR55 or affected by nitric oxide synthase
      (NOS) inhibition. However, the vasorelaxant effects of Abn-CBD were abolished
      when the endothelium was removed and were inhibited by the small Ca(2+)-sensitive
      K channel (SKCa) blocker, apamin. The effects of the endogenous endocannabinoid
      metabolite, N-arachidonyl glycine (NAGly), a putative agonist for GPR18, were
      virtually identical to those of Abn-CBD. GPR18 mRNA and protein were present in
      the retina, and immunohistochemistry demonstrated that GPR18 was localized to the
      endothelium of retinal vessels. These findings demonstrate that Abn-CBD and NAGly
      inhibit ET-1 induced vasoconstriction in retinal arterioles by an endothelium
      dependent signaling mechanism that involves SKCa channels. The endothelial
      localization of GPR18 suggests that GPR18 could contribute to cannabinoid and
      lipid-mediated retinal vasoactivity. 

PMID- 24751712
TI  - Hesperetin inhibits rat coronary constriction by inhibiting Ca(2+) influx and
      enhancing voltage-gated K(+) channel currents of the myocytes.
AB  - Hesperetin (HSP, one of the most common flavonoids in Citrus) has been reported
      to possess many benificial effects and is indicated for many diseases both as a
      therapeutic drug and as a supplement. Although its vascular effects have been
      extensively studied, little is known about its effects and the underlying
      mechanisms on coronary artery. In the present study, the myogenic effects of HSP
      were studied with a wire myograph in isolated rat coronary artery (RCA).
      Molecular probe and the patch clamp technique were used to study effects of HSP
      on intracellular free Ca(2+) concentration, inward Ca(2+) currents through L-type
      voltage-gated Ca(2+) channels (LVGC) and outward K(+) currents through voltage
      gated K(+) channels (KV). HSP (0.01-0.1mM) concentration-dependently depressed
      concentration-contraction curves of both KCl and thromboxane receptor agonist
      9,11-Dideoxy-9alpha,11alpha-methanoepoxy prostaglandin F2alpha (U46619), and
      relaxed RCA precontracted by the both vasoconstrictors. The vasospasmolytic
      effect was more potent in KCl- than in U46619-induced contraction. The
      vasorelaxation was attenuated by 4-aminopyridine, a specific KV inhibitor, but
      not affected by NG-nitro-L-arginine methylester ester, indomethacin,
      glibenclamide, iberiotoxin, BaCl2 or endothelium denudation. At the same
      concentrations, HSP inhibited extracellular Ca(2+) influx-induced contraction,
      reduced intracellular free Ca(2+) concentration, inhibited inward Ca(2+) currents
      through LVGC and increased outward K(+) currents through KV in the vascular
      smooth muscle cells (VSMCs) freshly isolated from RCA. Collectively, our results
      show that HSP is vasospasmolytic in RCA and suggest that the vasospasmolysis is
      mediated by inhibition of LVGC and enhancement of KV currents in RCA VSMCs. 

PMID- 24751713
TI  - Emodin accentuates atrial natriuretic peptide secretion in cardiac atria.
AB  - Emodin, an active anthraquinone constituent isolated from the rhubarb, a
      traditional Chinese herbal medicine which is widely used in clinical treatment,
      has cardiovascular protective properties. However, it remains unclear whether the
      cardiovascular protective actions of emodin are related to an activation of
      cardiac natriuretic hormone secretion. The purpose of the present study was to
      explore the effect of emodin on the secretion of ANP, a member of the family of
      cardiac natriuretic hormones, and its mechanisms involved. Experiments were
      performed in isolated perfused beating rabbit atria allowing measurement of ANP
      secretion, atrial pulse pressure, and stroke volume. Emodin increased ANP
      secretion concomitantly with a decrease in atrial pulse pressure and stroke
      volume in a concentration-dependent manner. These effects were reversible.
      Inhibition of K(+) channels with tetraethylammonium and glibenclamide attenuated
      the emodin-induced changes in ANP secretion and atrial dynamics. Furthermore, the
      emodin-induced changes in ANP secretion and atrial dynamics were attenuated by
      inhibition of L-type Ca(2+) channels with nifedipine. Atropine, methoctramine,
      tertiapin-Q, and pertussis toxin had no significant effect on the emodin-induced
      changes in ANP secretion and mechanical dynamics. The present study demonstrates
      that emodin increases ANP secretion via inhibition of L-type Ca(2+) channels
      through an activation of K(+)ATP channel in isolated beating rabbit atria. The
      results also provide a rationale for the use of emodin in the treatment of
      impairment of the regulation of the cardiovascular homeostasis. 

PMID- 24751714
TI  - Antiarrhythmic, hypotensive and alpha1-adrenolytic properties of new 2
      methoxyphenylpiperazine derivatives of xanthone.
AB  - The main goal of this study was to assess antiarrhythmic and hypotensive activity
      of new 2-methoxyphenylpiperazine derivatives of xanthone. In order to better
      understand mechanism of action of studied compounds, their abilities to
      antagonize the increase in blood pressure elicited by adrenaline, noradrenaline
      and methoxamine, as well as the antagonistic properties for alpha1-adrenoceptors
      on isolated rat aorta were evaluated. Therapeutic antiarrhythmic activity was
      investigated in an adrenaline-induced model of arrhythmia. Hypotensive activity
      in normotensive rats was evaluated after oral administration. Influence on blood
      vasopressor response and alpha1-adrenoceptors in rat thoracic aorta was evaluated
      to determine if the observed cardiovascular effects could be related to alpha1
      adrenolytic properties. Tested compounds produced antiarrhythmic and hypotensive
      activity. The most active compound was MH-99 - (R,S)-4-(2-hydroxy-3-(4-(2
      methoxyphenyl)piperazine-1-yl)propoxy)-9H-xanthen-9-one hydrochloride. All
      studied compounds showed alpha1-adrenolytic properties in the in vivo and in
      vitro tests. The results indicate that the new valuable compounds with
      antiarrhythmic and hypotensive activity might be found in the group of xanthone
      derivatives. Further pharmacological utility of these compounds should be
      investigated. 

PMID- 24751715
TI  - Development of VHH antibodies against dengue virus type 2 NS1 and comparison with
      monoclonal antibodies for use in immunological diagnosis.
AB  - The possibility of using variable domain heavy-chain antibodies (VHH antibodies)
      as diagnostic tools for dengue virus (DENV) type 2 NS1 protein was investigated
      and compared with the use of conventional monoclonal antibodies. After successful
      expression of DENV type 2 NS1 protein, the genes of VHH antibodies against NS1
      protein were biopanned from a non-immune llama library by phage display. VHH
      antibodies were then expressed and purified from Escherichia coli.
      Simultaneously, monoclonal antibodies were obtained by the conventional route.
      Sequence analysis of the VHH antibodies revealed novel and long complementarity
      determining regions 3 (CDR3). Epitope mapping was performed via a phage display
      peptide library using purified VHH and monoclonal antibodies as targets.
      Interestingly, the same region of NS1, which comprises amino acids
      224HWPKPHTLW232, was conserved for both kinds of antibodies displaying the
      consensus motif histidine-tryptophan-tryptophan or tryptophan-proline-tryptophan.
      The two types of antibodies were used to prepare rapid diagnostic kits based on
      immunochromatographic assay. The VHH antibody immobilized rapid diagnostic kit
      showed better sensitivity and specificity than the monoclonal antibody
      immobilized rapid diagnostic kit, which might be due to the long CDR3 regions of
      the VHH antibodies and their ability to bind to the pocket and cleft of the
      targeted antigen. This demonstrates that VHH antibodies are likely to be an
      option for developing point-of-care tests against DENV infection. 

PMID- 24751717
TI  - Estimate of venous thromboembolism and related-deaths attributable to the use of
      combined oral contraceptives in France.
AB  - PURPOSE: To estimate the number of venous thromboembolic events and related
      premature mortality (including immediate in-hospital lethality) attributable to
      the use of combined oral contraceptives in women aged 15 to 49 years-old between
      2000 and 2011 in France. METHODS: French data on sales of combined oral
      contraceptives and on contraception behaviours from two national surveys
      conducted in 2000 and 2010 were combined to estimate the number of exposed women
      according to contraceptives generation and age. Absolute risk of first time
      venous thromboembolism in non-users of hormonal contraception and increased risk
      of thromboembolism in users vs. non-users of hormonal contraception were
      estimated on the basis of literature data. Finally, immediate in-hospital
      lethality due to pulmonary embolism and premature mortality due to recurrent
      venous thromboembolism were estimated from the French national database of
      hospitalisation and literature data. RESULTS: In France, more than four million
      women are daily exposed to combined oral contraceptives. The mean annual number
      of venous thromboembolic events attributable to their use was 2,529 (778
      associated to the use of first- and second-generation contraceptives and 1,751 to
      the use of third- and fourth-generation contraceptives), corresponding to 20
      premature deaths (six with first- and second-generation contraceptives and
      fourteen with third- and fourth-generation contraceptives), of which there were
      eight to nine immediate in-hospital deaths. As compared to the use of first- and
      second-generation contraceptives, exposure to third- and fourth-generation
      contraceptives led to a mean annual excess of 1,167 venous thromboembolic events
      and nine premature deaths (including three immediate in-hospital deaths).
      CONCLUSIONS: Corrective actions should be considered to limit exposure to third-
      and fourth-generation contraceptives, and thus optimise the benefit-risk ratio of
      combined oral contraception.

PMID- 24751716
TI  - SETD6 controls the expression of estrogen-responsive genes and proliferation of
      breast carcinoma cells.
AB  - The lysine methyltransferase SETD6 modifies the histone variant H2AZ, a key
      component of nuclear receptor-dependent transcription. Herein, we report the
      identification of several factors that associate with SETD6 and are implicated in
      nuclear hormone receptor signaling. Specifically, SETD6 associates with the
      estrogen receptor alpha (ERalpha), histone deacetylase HDAC1, metastasis protein
      MTA2, and the transcriptional co-activator TRRAP. Luciferase reporter assays
      identify SETD6 as a transcriptional repressor, in agreement with its association
      with HDAC1 and MTA2. However, SETD6 behaves as a co-activator of several estrogen
      responsive genes, such as PGR and TFF1. Consistent with these results, silencing
      of SETD6 in several breast carcinoma cell lines induced cellular proliferation
      defects accompanied by enhanced expression of the cell cycle inhibitor CDKN1A and
      induction of apoptosis. Herein, we have identified several chromatin proteins
      that associate with SETD6 and described SETD6 as an essential factor for nuclear
      receptor signaling and cellular proliferation. 

PMID- 24751718
TI  - Characterization of mammalian selenoprotein o: a redox-active mitochondrial
      protein.
AB  - Selenoproteins exhibit diverse biological functions, most of which are associated
      with redox control. However, the functions of approximately half of mammalian
      selenoproteins are not known. One such protein is Selenoprotein O (SelO), the
      largest mammalian selenoprotein with orthologs found in a wide range of
      organisms, including bacteria and yeast. Here, we report characterization of
      mammalian SelO. Expression of this protein could be verified in HEK 293T cells by
      metabolic labeling of cells with 75Se, and it was abolished when selenocysteine
      was replaced with serine. A CxxU motif was identified in the C-terminal region of
      SelO. This protein was reversibly oxidized in a time- and concentration-dependent
      manner in HEK 293T cells when cells were treated with hydrogen peroxide. This
      treatment led to the formation of a transient 88 kDa SelO-containing complex. The
      formation of this complex was enhanced by replacing the CxxU motif with SxxC, but
      abolished when it was replaced with SxxS, suggesting a redox interaction of SelO
      with another protein through its Sec residue. SelO was localized to mitochondria
      and expressed across mouse tissues. Its expression was little affected by
      selenium deficiency, suggesting it has a high priority for selenium supply. Taken
      together, these results show that SelO is a redox-active mitochondrial
      selenoprotein. 

PMID- 24751719
TI  - Gankyrin is frequently overexpressed in cervical high grade disease and is
      associated with cervical carcinogenesis and metastasis.
AB  - Our previous studies have showed that Gankyrin expression is correlated with a
      malignant phenotype in endometrial carcinoma. Here, we investigated the possible
      role of Gankyrin in cervical disease. The increasing protein level of Gankyrin
      was observed in high-grade cervical intraepithelial neoplasia and carcinoma
      compared with benign cervical tissues and low-grade cervical intraepithelial
      neoplasia. In para-carcinoma tissues, it was found interestingly that there was
      no lymph node metastasis when nuclei Gankyrin was positively expressed, but lymph
      node metastasis rate was 30% (6/20) when nuclei Gankyrin was negatively
      expressed. In vitro, the transfection of Gankyrin resulted in markedly up
      regulating of Vimentin, beta-catenin and Twist2, as well as down-regulating of E
      cadherin in cervical carcinoma cells. Our results suggested that Gankyrin may be
      functional in cervical carcinogenesis and metastasis. 

PMID- 24751720
TI  - Designing mixed species tree plantations for the tropics: balancing ecological
      attributes of species with landholder preferences in the Philippines.
AB  - A mixed species reforestation program known as the Rainforestation Farming system
      was undertaken in the Philippines to develop forms of farm forestry more suitable
      for smallholders than the simple monocultural plantations commonly used then. In
      this study, we describe the subsequent changes in stand structure and floristic
      composition of these plantations in order to learn from the experience and
      develop improved prescriptions for reforestation systems likely to be attractive
      to smallholders. We investigated stands aged from 6 to 11 years old on three
      successive occasions over a 6 year period. We found the number of species
      originally present in the plots as trees >5 cm dbh decreased from an initial
      total of 76 species to 65 species at the end of study period. But, at the same
      time, some new species reached the size class threshold and were recruited into
      the canopy layer. There was a substantial decline in tree density from an
      estimated stocking of about 5000 trees per ha at the time of planting to 1380
      trees per ha at the time of the first measurement; the density declined by a
      further 4.9% per year. Changes in composition and stand structure were indicated
      by a marked shift in the Importance Value Index of species. Over six years, shade
      intolerant species became less important and the native shade-tolerant species
      (often Dipterocarps) increased in importance. Based on how the Rainforestation
      Farming plantations developed in these early years, we suggest that mixed-species
      plantations elsewhere in the humid tropics should be around 1000 trees per ha or
      less, that the proportion of fast growing (and hence early maturing) trees should
      be about 30-40% of this initial density and that any fruit tree component should
      only be planted on the plantation margin where more light and space are available
      for crowns to develop. 

PMID- 24751721
TI  - Mannose binding lectin and susceptibility to rheumatoid arthritis in Brazilian
      patients and their relatives.
AB  - INTRODUCTION: Rheumatoid arthritis (RA) is a commonly occurring systemic
      inflammatory auto immune disease and is believed to be associated with genetic
      factors. The innate immune complement protein Mannose binding lectin (MBL) and
      their MBL2 genetic variants are associated with different infectious and
      autoimmune diseases. METHODS: In a Brazilian cohort, we aim to associate the
      functional role of circulating MBL serum levels and MBL2 variants in clinically
      classified patients (n = 196) with rheumatoid arthritis including their relatives
      (n = 200) and ethnicity matched healthy controls (n = 200). MBL serum levels were
      measured by ELISA and functional MBL2 variants were genotyped by direct
      sequencing. RESULTS: The exon1+54 MBL2*B variant was significantly associated
      with an increased risk and the reconstructed haplotype MBL2*LYPB was associated
      with RA susceptibility. Circulating serum MBL levels were observed significantly
      lower in RA patients compared to their relatives and controls. No significant
      contribution of MBL levels were observed with respect to functional class, age at
      disease onset, disease duration and/or other clinical parameters such as nodules,
      secondary Sjogren syndrome, anti-CCP and rheumatoid factor. Differential
      distribution of serum MBL levels with functional MBL2 variants was observed in
      respective RA patients and their relatives. CONCLUSIONS: Our results suggest MBL
      levels as a possible marker for RA susceptibility in a Brazilian population.

PMID- 24751722
TI  - Heterosis may result in selection favouring the products of long-distance pollen
      dispersal in Eucalyptus.
AB  - Using native trees from near the northern and southern extremities of the
      relatively continuous eastern distribution of Eucalyptus globulus in Tasmania, we
      compared the progenies derived from natural open-pollination (OP) with those
      generated from within-region and long-distance outcrossing. Controlled
      outcrossing amongst eight parents - with four parents from each of the northern
      and southern regions - was undertaken using a diallel mating scheme. The progeny
      were planted in two field trials located within the species native range in
      southern Tasmania, and their survival and diameter growth were monitored over a
      13-year-period. The survival and growth performances of all controlled cross
      types exceeded those of the OP progenies, consistent with inbreeding depression
      due to a combination of selfing and bi-parental inbreeding. The poorer survival
      of the northern regional (?N?N) outcrosses compared with the local southern
      regional outcrosses (?S?S) indicated differential selection against the former.
      Despite this mal-adaptation of the non-local ?N?N crosses at both southern sites,
      the survival of the inter-regional hybrids (?N?S and ?S?N) was never
      significantly different from that of the local ?S?S crosses. Significant site
      dependent heterosis was detected for the growth of the surviving long-distance
      hybrids. This was expressed as mid-parent heterosis, particularly at the more
      northern planting site. Heterosis increased with age, while the difference
      between the regional ?N?N and ?S?S crosses remained insignificant at any age at
      either site. Nevertheless, the results for growth suggest that the fitness of
      individuals derived from long-distance crossing may be better at the more
      northern of the planting sites. Our results demonstrate the potential for early
      age assessments of pollen dispersal to underestimate realised gene flow, with
      local inbreeding under natural open-pollination resulting in selection favouring
      the products of longer-distance pollinations. Indeed, heterosis derived from long
      distance pollinations may be sufficient to counter local mal-adaptation, at least
      in the first generation. 

PMID- 24751723
TI  - Rate of ascent and acute mountain sickness at high altitude.
AB  - OBJECTIVE: To examine the effect of ascent rate on the induction of acute
      mountain sickness (AMS) in young adults during a climb to Jiaming Lake (3350 m)
      in Taiwan. DESIGN: Prospective, nonrandomized. SETTING: Climb from 2370 to 3350
      m. PARTICIPANTS: Young adults (aged 18 to 26 years) (N = 91) chose to participate
      in either the fast ascent (3 days; n = 43) or slow ascent (4 days; n = 48) group
      (1 and 2). ASSESSMENT OF RISK FACTORS: Two criteria were used to define AMS. A
      Lake Louise score >=3 and Lake Louise criteria [in the setting of a recent gain
      in altitude, the presence of headache and at least 1 of gastrointestinal
      discomfort (anorexia, nausea, or vomiting), fatigue or weakness, dizziness or
      lightheadedness, or difficulty sleeping]. MAIN OUTCOME MEASURES: Heart rate,
      blood oxygen saturation (SaO2), and symptoms of AMS were monitored each morning
      and evening. RESULTS: Baseline characteristics were similar between groups,
      except for significant differences in history of alcohol consumption (P = 0.009)
      and climbing experience above 3000 m (P < 0.001). The incidence of AMS was not
      associated with the rate of ascent. Acute mountain sickness was most prevalent in
      group 1 on day 2 in the evening and in group 2 on day 3 in the evening. In both
      groups, AMS correlated with the initial reduction in SaO2. Body mass index (BMI)
      >24 kg/m was identified as a significant risk factor for AMS. CONCLUSIONS: The
      development of AMS was closely associated with an initial reduction in SaO2. A
      BMI >24 kg/m also contributed to the occurrence of AMS. CLINICAL RELEVANCE: These
      findings indicate that factors other than ascent rate should be considered when
      trying to ameliorate the risk of AMS.

PMID- 24751724
TI  - Does ethnicity affect where people with cancer die? A population-based 10 year
      study.
AB  - BACKGROUND: Ageing is a growing issue for people from UK black, Asian and
      minority ethnic (BAME) groups. The health experiences of these groups are
      recognised as a 'tracer' to measure success in end of life patient-preferred
      outcomes that includes place of death (PoD). AIM: To examine patterns in PoD
      among BAME groups who died of cancer. MATERIAL AND METHODS: Mortality data for
      93,375 cancer deaths of those aged >=65 years in London from 2001-2010 were
      obtained from the UK Office for National Statistics (ONS). Decedent's country of
      birth was used as a proxy for ethnicity. Linear regression examined trends in
      place of death across the eight ethnic groups and Poisson regression examined the
      association between country of birth and place of death. RESULTS: 76% decedents
      were born in the UK, followed by Ireland (5.9%), Europe(5.4%) and
      Caribbean(4.3%). Most deaths(52.5%) occurred in hospital, followed by
      home(18.7%). During the study period, deaths in hospital declined with an
      increase in home deaths; trend for time analysis for those born in
      UK(0.50%/yr[0.36-0.64%]p<0.001), Europe (1.00%/yr[0.64-1.30%]p<0.001),
      Asia(1.09%/yr[0.94-1.20%]p<0.001) and Caribbean(1.03%/yr[0.72-1.30%]p<0.001).
      However, time consistent gaps across the geographical groups remained. Following
      adjustment hospital deaths were more likely for those born in Asia(Proportion
      ratio(PR)1.12[95%CI1.08-1.15]p<0.001) and Africa(PR 1.11[95%CI1.07-1.16]p<0.001).
      Hospice deaths were less likely for those born in Asia(PR 0.73 [0.68-0.80]
      p<0.001), Africa (PR 0.83[95%CI0.74-0.93]p<0.001), and 'other' geographical
      regions (PR0.90[95% 0.82-0.98]p<0.001). Home deaths were less likely for those
      born in the Caribbean(PR0.91[95%CI 0.85-0.98]p<0.001). CONCLUSIONS: Location of
      death varies by country of birth. BAME groups are more likely to die in a
      hospital and less likely to die at home or in a hospice. Further investigation is
      needed to determine whether these differences result from patient-centred
      preferences, or other environment or service-related factors. This knowledge will
      enable strategies to be developed to improve access to relevant palliative care
      and related services, where necessary.

PMID- 24751725
TI  - Genome-wide DNA methylation in neonates exposed to maternal depression, anxiety,
      or SSRI medication during pregnancy.
AB  - Despite the high prevalence of depression, anxiety, and use of antidepressant
      medications during pregnancy, there is much uncertainty around the impact of high
      levels of distress or antidepressant medications on the developing fetus. These
      intrauterine exposures may lead to epigenetic alterations to the DNA during this
      vulnerable time of fetal development, which may have important lifetime health
      consequences. In this study we investigated patterns of genome-wide DNA
      methylation using the Illumina Infinium Human Methylation450 BeadChip in the
      umbilical cord blood of neonates exposed to non-medicated maternal depression or
      anxiety (n = 13), or selective serotonin reuptake inhibitors (SSRIs) during
      pregnancy (n = 22), relative to unexposed neonates (n = 23). We identified 42 CpG
      sites with significantly different DNA methylation levels in neonates exposed to
      non-medicated depression or anxiety relative to controls. CpG site methylation
      was not significantly different in neonates exposed to SSRIs relative to the
      controls, after adjusting for multiple comparisons. In neonates exposed either to
      non-medicated maternal depression or SSRIs, the vast majority of CpG sites
      displayed lower DNA methylation relative to the controls, but differences were
      very small. A gene ontology analysis suggests significant clustering of the top
      genes associated with non-medicated maternal depression/anxiety, related to
      regulation of transcription, translation, and cell division processes (e.g.,
      negative regulation of translation in response to oxidative stress, regulation of
      mRNA export from the nucleus, regulation of stem cell division). While the
      functional consequences of these findings are yet to be determined, these small
      DNA methylation differences may suggest a possible role for epigenetic processes
      in the development of neonates exposed to non-medicated maternal
      depression/anxiety. 

PMID- 24751726
TI  - TSLP induces mast cell development and aggravates allergic reactions through the
      activation of MDM2 and STAT6.
AB  - Thymic stromal lymphopoietin (TSLP) is known to promote T helper type 2 cell
      associated inflammation. Mast cells are major effector cells in allergic
      inflammatory responses. We noted that the population and maturation of mast cells
      were reduced in TSLP-deficient mice (TSLP-/-). Thus, we hypothesized that TSLP
      might affect mast cell development. We found that TSLP induced the proliferation
      and differentiation of mast cells from bone marrow progenitors. TSLP-induced mast
      cell proliferation was abolished by depletion of mouse double minute 2 (MDM2) and
      signal transducers and activators of transcription 6 (STAT6), as an upstream
      activator of MDM2. TSLP-/-, in particular, had a considerable deficit in the
      expression of MDM2 and STAT6. Also, the TSLP deficiency attenuated mast cell
      mediated allergic reactions through the downregulation of STAT6 and MDM2. In an
      antibody microarray chip analysis, MDM2 expression was increased in atopic
      dermatitis patients. These observations indicate that TSLP is a factor for mast
      cell development, and that it aggravates mast cell-mediated immune responses. 

PMID- 24751727
TI  - Loss of keratin K2 expression causes aberrant aggregation of K10, hyperkeratosis,
      and inflammation.
AB  - Keratin K2 is one of the most abundant structural proteins of the epidermis;
      however, its biological significance has remained elusive. Here we show that
      suprabasal type II keratins, K1 and K2, are expressed in a mutually exclusive
      manner at different body sites of the mouse, with K2 being confined to the ear,
      sole, and tail skin. Deletion of K2 caused acanthosis and hyperkeratosis of the
      ear and the tail epidermis, corneocyte fragility, increased transepidermal water
      loss, and local inflammation in the ear skin. The loss of K2 was partially
      compensated by upregulation of K1 expression. However, a significant portion of
      K2-deficient suprabasal keratinocytes lacked a regular cytoskeleton and developed
      massive aggregates of the type I keratin, K10. Aggregate formation, but not
      hyperkeratosis, was suppressed by the deletion of both K2 and K10, whereas
      deletion of K10 alone caused clumping of K2 in ear skin. Taken together, this
      study demonstrates that K2 is a necessary and sufficient binding partner of K10
      at distinct body sites of the mouse and that unbalanced expression of these
      keratins results in aggregate formation. 

PMID- 24751728
TI  - Molecular characterization of human skin response to diphencyprone at peak and
      resolution phases: therapeutic insights.
AB  - Diphencyprone (DPCP) is a hapten that induces delayed-type hypersensitivity (DTH)
      reactions. It is used as an immune-modulating therapeutic, but its molecular
      effects in human skin are largely unknown. We studied cellular and molecular
      characteristics of a recall response to 0.04% DPCP at 3-day (peak) and 14-day
      (resolution) time points using immune markers, reverse-transcriptase-PCR (RT
      PCR), and gene array approaches. A peak response showed modulation of ~7,500 mRNA
      transcripts, with high expression of cytokines that define all major effector T
      cell subsets. Concomitant increases in T-cell and CD11c+ dendritic cell (DC)
      infiltrates were measured. The resolution reaction was characterized by
      unexpectedly high levels of T cells and mature (DC-lysosome-associated membrane
      glycoprotein positive (DC-LAMP+)) DCs, but with marked decreases in expression of
      IL-2, IFNgamma, and other T cell-derived cytokines. However, negative immune
      regulators such as IDO1 that were high in peak reactions, continued to have high
      expression in resolution reactions. In the resolution reaction, ~1,500 mRNA
      transcripts were significantly different from placebo-treated skin. These data
      suggest that the response to DPCP evolves from an inflammatory/effector peak at
      day 3 to a more regulated immune response after 14 days. This model system could
      be useful for further dissection of mechanisms of immune activation or negative
      immune regulation in human skin. 

PMID- 24751729
TI  - Next-generation sequencing of nevus spilus-type congenital melanocytic nevus:
      exquisite genotype-phenotype correlation in mosaic RASopathies.

PMID- 24751731
TI  - In vivo wound healing performance of drug loaded electrospun composite nanofibers
      transdermal patch.
AB  - Acute injuries or wound is required the fast delivery of drug to control
      infections without any side effect. In this direction in the present
      investigation, antibiotic ciprofloxacin loaded hydrophilic biodegradable poly
      vinyl alcohol (PVA) and sodium alginate (NaAlg) electrospun composite nanofiber
      based transdermal patch was developed for local delivery of antibiotic drug. The
      antibiotic drug ciprofloxacin was loaded in it by active loading. The drug
      entrapped in the composite nanofibers was confirmed by the scanning electron
      microscopy and swelling behavior. The in vivo studies were carried on male
      rabbits by using the drug loaded and unloaded composite nanofibers transdermal
      patch and marketed one. It is observed that, in vitro activity provides a
      sustained and controlled release pattern of the drug from transdermal patch. The
      mechanism of drug release was also studied using different models. The nanofiber
      transdermal patch follows the Higuchi and Korsmeyer-Peppas model for drug
      release. The in vivo studies demonstrate that, wound healing takes place in less
      time as compared drug unloaded patch. Hydroxyproline produced in wound bed with
      time shows that it content is maximum in case drug loaded PAV-NaAlg patch. This
      demonstrates that wound healing rate is higher in case drug loaded PVA-NaAlg
      transdermal patch.

PMID- 24751730
TI  - Imiquimod inhibits melanoma development by promoting pDC cytotoxic functions and
      impeding tumor vascularization.
AB  - Imiquimod (IMQ) is a synthetic Toll-like receptor (TLR7/8) ligand that can
      trigger antiviral and antitumor activities. Despite evidence of potent
      therapeutic effects, the clinical use of IMQ in melanoma is impeded by incomplete
      understanding of its mechanisms of action. Mice and humans differ in many aspects
      of immunity, including TLR7 expression patterns, thus impeding the use of mouse
      models in translating discoveries into clinical applications. In this article, we
      investigated the mechanisms behind IMQ effects in vivo in a human context of
      melanoma and immunity using an innovative melanoma-bearing humanized mouse model.
      In this model, IMQ strongly inhibited melanoma tumor development through prompt
      mobilization of plasmacytoid dendritic cells and by triggering their cytotoxic
      functions, and through upregulation of expression of type 1 IFN response genes.
      IMQ also drastically impeded tumor vascularization by inducing the downregulation
      of angiogenic factors vascular endothelial growth factor, angiogenin, IL-8, and
      fibroblast growth factor. Our results revealed the short- and long-term
      multifactorial effects of IMQ converging toward inhibition of melanoma
      development. By providing a better understanding of the mechanisms of action of
      IMQ in melanoma, our study opens the way for its further clinical use in the
      treatment of metastatic melanoma. 

PMID- 24751732
TI  - Optimization of secondary drying condition for desired residual water content in
      a lyophilized product using a novel simulation program for pharmaceutical
      lyophilization.
AB  - The aim of this study was to optimize the shelf temperature and the drying time,
      mainly dependent on the residual water content of a lyophilized product using a
      novel simulation program for the secondary drying of lyophilization. The
      simulation program was developed based upon heat transfer formulas, two empirical
      formulas, and a modified Fick's second law. When a preliminary lyophilization run
      of secondary drying was carried out, the equilibrium product temperature at the
      end of secondary drying under various shelf temperatures was accurately predicted
      by the heat transfer formulas. The apparent diffusion coefficient of water, Deff,
      and the apparent equilibrium residual water content, We, under the predicted
      equilibrium product temperature were estimated by two empirical formulas. These
      estimated Deff and We allow the modified Fick's second law to predict the
      residual water content in the lyophilized product. Using the developed simulation
      program, it was verified that the secondary drying condition to achieve the
      desired residual water content in the lyophilized product was successfully
      predicted. Therefore, the simulation program can be used to effectively design
      the secondary drying condition of lyophilization cycles without a trial and error
      approach. 

PMID- 24751733
TI  - Long-term subjective benefit with a bone conduction implant sound processor in 44
      patients with single-sided deafness.
AB  - INTRODUCTION: Studies that investigate the subjective benefit from a bone
      conduction implant (BCI) sound processor in patients with single-sided
      sensorineural deafness (SSD) have been limited to examining short- and mid-term
      benefit. In the current study, we performed a survey among 44 SSD BCI users with
      a median follow-up time of 50 months. MATERIALS AND METHODS: Forty-four
      experienced SSD BCI users participated in the survey, which consisted of the
      Abbreviated Profile of Hearing Aid Benefit, the Single-Sided Deafness
      Questionnaire, the Short Hearing Handicap Inventory for Adults, and a self-made
      user questionnaire. For patients with tinnitus, the Tinnitus Questionnaire was
      also completed. The results of the survey were correlated with contralateral
      hearing loss, age at implantation, duration of the hearing loss at the time of
      implantation, duration of BCI use, and the presence and burden of tinnitus.
      RESULTS: In total, 86% of the patients still used their sound processor. The
      Abbreviated Profile of Hearing Aid Benefit and the Short Hearing Handicap
      Inventory for Adults show a statistically significant overall improvement with
      the BCI. The Single-Sided Deafness Questionnaire and the user questionnaire
      showed that almost 40% of the patients reported daily use of the sound processor.
      However, the survey of daily use reveals benefit only in certain circumstances.
      Speech understanding in noisy situations is rated rather low, and 58% of all
      patients reported that their BCI benefit was less than expected. CONCLUSION: The
      majority of the patients reported an overall improvement from using their BCI.
      However, the number of users decreases during a longer follow-up time and
      patients get less enthusiastic about the device after an extended period of use,
      especially in noisy situations. However, diminished satisfaction because of time
      related reductions in processor function could not be ruled out.

PMID- 24751734
TI  - Voluntary eardrum movement: a marker for tensor tympani contraction?
AB  - HYPOTHESIS: Voluntary eardrum movement (VEM) and resultant tympanometric changes
      reflect tensor tympani (TT) contraction. BACKGROUND: TT contraction has been
      hypothesized to cause symptoms of aural fullness, tinnitus, clicking, and even
      vertigo despite the lack of understanding of how it functions or what causes it
      to contract. Identifying tympanometric changes unique to TT contraction can
      provide a diagnostic tool for identifying its role in pathologic conditions.
      METHODS: Various tympanometric measurements were performed on human subjects who
      could voluntarily move their eardrums. These were compared with similar
      tympanometric measurements performed on cadaveric temporal bones while manually
      tensing the TT and stapedius muscles individually. RESULTS: Eight subjects (14
      ears) who could cause VEM were identified. Compared with baseline, VEM resulted
      in significantly decreased middle ear compliance (p < 0.01) and middle ear
      pressure (p < 0.01) measurements. The compliance changes seen with VEM were
      larger than those seen with acoustically stimulated stapedius contraction.
      Finally, the direction of compliance change with VEM was dependent on the
      pressure applied to the external auditory canal (EAC), with compliance increasing
      with positive EAC pressure. This was not seen with stapedius contraction. These
      findings were reproduced using the cadaveric temporal bone model: larger
      compliance changes with pull on TT as compared with stapedius with neutral EAC
      probe pressure; change in direction of compliance changes with varying EAC probe
      pressure with TT pull, not with stapedius pull. CONCLUSION: TT contraction
      produces distinctive tympanometric findings that can be used to support its
      abnormal contraction in ears with symptoms compatible with TT syndrome.

PMID- 24751735
TI  - The role of wait-and-scan and the efficacy of radiotherapy in the treatment of
      temporal bone paragangliomas.
AB  - OBJECTIVE: To define the role of wait-and-scan and radiotherapy (RT) in the
      treatment of temporal bone paragangliomas and to review the literature on the
      outcomes of RT as a treatment modality. MATERIALS AND METHODS: This was a
      retrospective and literature review. The records of 381 patients with 382 tumors
      between 1988 and 2012 were analyzed. Patients who were subjected to initial wait
      and-scan or primary RT were analyzed for tumor response, facial, and lower
      cranial nerve status on follow-up (FU). RESULTS AND OBSERVATIONS: None of the 145
      patients (38%) with Class A and B tumors were subjected to wait-and-scan or RT
      and all were operated on. Of the 237 patients (62%) with Class C and D tumors, 47
      (19.8%) were subjected to an initial wait-and-scan policy and 1 (0.4%) underwent
      primary RT. In 24 patients subjected to wait-and-scan with a FU of less than 3
      years, tumor remained stable in 22 patients (92%). In 12 patients with a FU
      between 3 and 5 years, the tumor remained stable or regressed in 10 patients
      (83%). In 11 patients with a FU of more than 5 years, the tumor remained stable
      or regressed in 5 patients (45%). A literature review of the results of RT did
      not conclusively prove that it was effective as a primary modality of treatment
      for temporal bone paragangliomas. CONCLUSION: In elderly patients with advanced
      tumors, a wait-and-scan approach is recommended, and RT is initiated only when
      fast-growing tumors are detected. There is insufficient evidence in literature to
      suggest that RT could be an effective alternative to surgery in Class C and D
      tumors.

PMID- 24751736
TI  - Safe levels of acoustic stimulation: comment on '"effects of acoustic stimuli
      used for vestibular evoked myogenic potential studies on the cochlear function
      '".

PMID- 24751737
TI  - Altered eustachian tube function in SCUBA divers with alternobaric vertigo.
AB  - OBJECTIVES: The number of people participating in sport self-contained underwater
      breathing apparatus (SCUBA) diving has increased tremendously, bringing with it a
      rise in diving accidents. Alternobaric vertigo (AV) is a common problem in SCUBA
      divers. We investigated the relationship between Eustachian tube function and
      incidence of AV in sport SCUBA divers. We also followed the progress of these
      divers after Eustachian tube function improved. METHOD: Forty-four patients who
      experienced a SCUBA diving accident affecting the middle ear (11 men and 33
      women; mean +/- SD: 37.5 +/- 11.5 yr) and 20 healthy volunteer divers who did not
      experience an accident (6 men and 14 women; mean +/- SD: 33.5 +/- 13.9 yr) were
      compared. We divided the divers with an accident into two groups (those with AV
      vs. those without) and then compared the two groups. All patients regularly
      underwent Eustachian tube function tests (sonotubometry and impedance test).
      RESULTS: In sonotubometry and impedance testing, the mean duration (p < 0.001),
      amplitude (p < 0.002), and maximum air content (p < 0.05) of divers who
      experienced a diving accident were significantly different from those of healthy
      volunteers. However, these parameters in divers with AV did not differ
      significantly from those in divers without AV. In 7 of 15 divers, vestibular
      symptoms disappeared immediately after ascent. In the remaining eight divers,
      however, vertigo/dizziness persisted and even was observed at their first clinic
      visit. CONCLUSION: To prevent AV or barotraumas in SCUBA divers, we recommend a
      thorough Eustachian tube function evaluation. Any dysfunction should be treated
      before engaging in SCUBA diving.

PMID- 24751738
TI  - Meningeal carcinomatosis of the internal auditory meatus: clinical and imagery
      aided differentiation.
AB  - OBJECTIVES: To describe difficulties in diagnosing meningeal carcinomatosis of
      the internal auditory meatus (IAM-MC). STUDY DESIGN: Retrospective case review.
      SETTING: Tertiary skull base surgery referral center. PATIENTS: A series of six
      cases of patients diagnosed with IAM-CM over 14 years. RESULTS: The primary
      cancer was known before diagnosis in three cases (adenocarcinoma of lung, breast,
      and melanoma). In two others, it was discovered at workup (lung, ethmoid
      adenocarcinoma). In the last case, no primary cancer was identified. Vestibular
      symptoms were the first complaint in five of the six cases. Referral symptom was
      facial paralysis in five cases and rapid-onset total deafness associated with
      severe unsteadiness in one. Rapid hearing decrease and symptoms of
      bilateralization were observed in five cases. Diagnosis was ascertained by
      discovery of malignant cells in the CSF in three cases and at tumor biopsy in one
      case. In the two other cases, the association of brain metastases and increased
      dura mater infiltration was convincing. Treatment consisted in radiation therapy
      to the whole brain in five cases and intrathecal chemotherapy in one case.
      Evolution was rapidly lethal in five cases. The last died free of disease 4 years
      after treatment. CONCLUSION: IAM-MC is difficult to demonstrate. Progressive
      facial paralysis associated with aggressive and rapidly bilateral cochlear and
      vestibular symptoms are highly evocative in the event of cancer in the patient's
      history. If there is no history of cancer, lumbar puncture is to be repeated
      until malignant cells are discovered in the CSF before beginning radiotherapy.

PMID- 24751739
TI  - Bifid facial nerve in congenital stapes footplate fixation.

PMID- 24751740
TI  - The use of cartilage in revision stapedectomy.
AB  - OBJECTIVE: To evaluate the incidence of stapedectomy patients who developed
      significant chronic ear disease resulting in reconstruction of the tympanic
      membrane with cartilage and concomitant revision stapedectomy. Audiometric
      results of this subgroup within revision stapedectomy are analyzed, and the
      salient features of the reconstruction method are discussed. STUDY DESIGN:
      Retrospective study of revision stapedectomy patients during the years 2003-2012.
      SETTING: Tertiary referral center. INTERVENTION: Cartilage tympanoplasty and
      revision stapedectomy. RESULTS: Seventeen patients (18 ears) of 144 revision
      stapes patients were studied who required cartilage tympanoplasty and revision
      stapedectomy. One-half underwent revision stapedectomy with a modified Lippy
      prosthesis (MLP), and one-half required a total ossicular prosthesis (TOP). The
      mean postoperative air-bone gap (ABG) was 11.1 dB with mean pure tone average
      (PTA) hearing improvement of 15.6 dB.The rate of ABG closure was 55.6% <10 dB and
      38.8 % >10 dB and <20 dB. CONCLUSION: The number of patients requiring revision
      stapedectomy due to significant chronic ear disease is small. This paper
      discusses the management and successful outcome of these more difficult
      revisions.

PMID- 24751741
TI  - Small vestibular schwannomas presenting with facial nerve palsy.
AB  - OBJECTIVE: To describe the surgical management and convalescence of two patients
      presenting with severe facial nerve weakness associated with small
      intracanalicular vestibular schwannomas (VS). STUDY DESIGN: Retrospective review.
      PATIENTS: Two adult female patients presenting with audiovestibular symptoms and
      subacute facial nerve paralysis (House-Brackmann Grade IV and V). In both cases,
      post-contrast T1-weighted magnetic resonance imaging revealed an enhancing lesion
      within the internal auditory canal without lateral extension beyond the fundus.
      INTERVENTION(S) AND RESULTS: Translabyrinthine exploration demonstrated
      vestibular nerve origin of tumor, extrinsic to the facial nerve, and frozen
      section pathology confirmed schwannoma. Gross total tumor resection with VIIth
      cranial nerve preservation and decompression of the labyrinthine segment of the
      facial nerve was performed. Both patients recovered full motor function between 6
      and 8 months after surgery. CONCLUSION: Although rare, small VS may cause severe
      facial neuropathy, mimicking the presentation of facial nerve schwannomas and
      other less common pathologies. In the absence of labyrinthine extension on MRI,
      surgical exploration is the only reliable means of establishing a diagnosis. In
      the case of confirmed VS, early gross total resection with facial nerve
      preservation and labyrinthine segment decompression may afford full motor
      recovery-an outcome that cannot be achieved with facial nerve grafting.

PMID- 24751742
TI  - A polymer-based multichannel cochlear electrode array.
AB  - OBJECTIVE: Compared with conventional cochlear electrode arrays, which are hand
      assembled and wire-based, polymer-based implants have several advantages. They
      are very precise, and their fabrication is inexpensive because of the use of thin
      film processes. In the present study, a cochlear electrode array based on a high
      performance liquid crystal polymer material is devised. Furthermore, the device
      is encapsulated in silicone elastomer. METHODS: The fabrication steps introduced
      here include thin-film processes with liquid crystal polymer (LCP) films and
      customized self-aligning molding processes for the electrode array. To assess the
      feasibility of the proposed electrode array, the charge storage capacitance and
      impedance were measured using a potentiostat. Vertical and horizontal deflection
      forces were measured using a customized fixture and a force sensor. Insertion and
      extraction forces were also measured using a transparent human cochlear plastic
      model, and five cases involving human temporal insertion trials were undertaken
      to assess the level of safety during the insertion process. RESULTS: The charge
      storage capacity and impedance at 1 kHz were 33.26 mC/cm and 1.02 kOmega,
      respectively. Likewise, the vertical force and horizontal force of the electrode
      array were 3.15 g and 1.07 g. The insertion force into a transparent plastic
      cochlear model with displacement of 8 mm from a round window was 8.2 mN, and the
      maximum extraction force was 110.4 mN. Two cases of human temporal bone insertion
      showed no observable trauma, whereas 3 cases showed a rupture of the basilar
      membrane. CONCLUSION: An LCP-based intracochlear electrode array was fabricated,
      and its electrical and mechanical properties were found to be suitable for
      clinical use.

PMID- 24751744
TI  - Vestibulotomy with ossiculoplasty versus round window vibroplasty procedure in
      children with oval window aplasia.
AB  - OBJECTIVE: To review the surgical procedures and outcomes in children with
      bilateral oval window aplasia (OWA). STUDY DESIGN: Retrospective cohort review.
      SETTING: Tertiary referral center. PATIENTS: Children suffering from OWA between
      1990 and 2010. INTERVENTION: Vestibulotomy with ossiculoplasty (V-OPL) or round
      window vibroplasty (RWV). MAIN OUTCOME MEASURES: Findings at radiology and
      surgery, preoperative and postoperative bone conduction (BC), air conduction
      (AC), and RWV-air conduction (RWV-AC) thresholds and speech discrimination scores
      (SDSs). RESULTS: Among 23 children, 11 underwent V-OPL and 8 RWV. Four children
      in the V-OPL group had aborted surgery and were excluded from the study. In all
      the remaining 19 children, the 6-month follow-up time showed postoperative AC and
      SDS values significantly better than the preoperative thresholds in both groups.
      At the 36-month long-term follow-up, AC and SDS were stable in the RWV group but
      showed a significant worsening in the V-OPL children compared with the 6-month
      follow-up results. Preoperative versus postoperative BC values showed a
      significant difference between the 2 groups at 36 months; 5 of the V-OPL group
      underwent revision following the same surgical principles, which did not result
      in improved outcome. CONCLUSION: In children with OWA, V-OPL provides modest long
      term results and carries higher risks of BC degradation compared to RWV. Both
      procedures are technically challenging but considering the respective hearing
      results and morbidity of primary and revision surgery, we have abandoned the V
      OPL procedure in favor of RWV. In infants and children younger than 5 years with
      OWA previously not considered candidates for hearing restoration, we consider RWV
      as the first-choice surgery. It has shown to provide significantly better hearing
      outcomes than traditional atresia surgery with minimal complication rate.

PMID- 24751743
TI  - Study of epithelial migration in the tympanic membrane and bony external auditory
      canal wall in patients with irradiated nasopharyngeal carcinoma.
AB  - OBJECTIVE: The objectives of this study were to determine the presence of
      epithelial migration in patients with postirradiated nasopharyngeal carcinoma
      (NPC) and to compare the rate of epithelial migration in the tympanic membrane
      (TM) and the bony external auditory canal (EAC) of postirradiated NPC ears with
      normal ears by means of the ink dot method. STUDY DESIGN: Prospective,
      nonrandomized case-control study involving patients with NPC and control subjects
      with healthy ears seen in an otorhinolaryngology outpatient clinic. SETTING:
      Otorhinolaryngology Outpatient Clinic, University Malaya Medical Centre, Kuala
      Lumpur. PATIENTS: Patients with NPC who have completed radiotherapy and patients
      with normal ear presenting with other complaints. INTERVENTION: Patients who
      fulfilled the inclusion and exclusion criteria were chosen for this study. All
      the selected patients' ears were visualized under a microscope and were cleaned,
      and ink dots were applied at the umbo and annulus. They were followed up on a 2-
      to 3-weekly basis until the ink dots reached the specified landmarks. The
      distance and pattern of migration were recorded and calculated. The mean
      radiation dose received by both the right and left TM and EAC was mapped and
      calculated. MAIN OUTCOME MEASURES: Rate and pattern of epithelial migration in
      the NPC group compared with that in the control group. RESULTS: The mean
      radiation dose to both the TM and EAC did not show a significant difference (p >
      0.05). The entire TM study group showed epithelial migration from the umbo toward
      the annulus and EAC, except in 1 ear. The mean rate of epithelial migration on
      the TM of the study group was 51.35 MUm/d compared with that on the control
      group, which was 64.68 MUm/d, and this difference was statistically significant
      (p < 0.05). Of the ears in the control group, 42.5% showed a migration pattern
      toward the posterior-superior direction, whereas 45% of the ears in the study
      group showed a migration pattern toward the posterior-inferior direction. In the
      EAC of the study group, the mean epithelial migration was noted to be accelerated
      compared to that of the control group (144.75 and 94.33 MUm/d, respectively; p <
      0.05). The mean rate of migration between the TM and the EAC was also different.
      Both the study and control groups showed a significant difference in migration,
      with a faster rate of migration in the EAC (p < 0.05). CONCLUSION: We noted a
      significant delay in the rate of epithelial migration in the TM of patients with
      postirradiated NPC and an accelerated rate of migration in the EAC of patients
      with postirradiated NPC. In addition, epithelial migration in the EAC was also
      noted to be faster than that in the TM of the control population.

PMID- 24751745
TI  - Efficacy of tympanoplasty without mastoidectomy on MRSA-infected chronic otitis
      media.
AB  - OBJECTIVES/HYPOTHESIS: The prevalence of methicillin-resistant Staphylococcus
      aureus (MRSA)-infected chronic otitis media (COM) has been increasing, but to
      date, there has been no consensus on surgical treatment. Although there is a
      report that mastoidectomy is essential in treating MRSA-infected COM, in our
      experience, we found that tympanoplasty without mastoidectomy was sufficient. In
      this study, we evaluated the efficacy of tympanoplasty without mastoidectomy on
      MRSA-infected COM. STUDY DESIGN: Retrospective case-control study. METHODS: Forty
      ears with MRSA-infected COM that underwent tympanoplasty without mastoidectomy
      were identified at a tertiary referral center from February 2006 to September
      2011. Each case had two controls matched. Hearing results and postoperative
      complication were examined to evaluate the efficacy of tympanoplasty. The
      preoperative and postoperative pure tone audiometry was checked. RESULTS: In the
      MRSA group and control group, 5 out of 40 ears (12.5%) and 8 out of 80 ears (10%)
      showed postoperative complications, respectively. The hearing success rate was
      95.8% (23/24) in the MRSA group and 91.7% (44/48) in the control group. In the
      MRSA group, the average air-bone gap was 20 dB preoperatively, and it improved to
      14 dB postoperatively. In the control group, the average air-bone gap was 19 dB
      preoperatively, and it improved to 13 dB postoperatively. There was no
      statistically significant difference between the MRSA and control groups.
      CONCLUSIONS: Tympanoplasty without mastoidectomy showed efficacy in MRSA-infected
      COM.

PMID- 24751746
TI  - Limited evidence for the effect of sodium fluoride on deterioration of hearing
      loss in patients with otosclerosis: a systematic review of the literature.
AB  - OBJECTIVE: To determine the protective effect of sodium fluoride on the
      deterioration of hearing loss in adult patients with otosclerosis. DATA SOURCES:
      PubMed, Embase, the Cochrane Library, and CINAHL. STUDY SELECTION: A systematic
      literature search was conducted. Studies reporting original study data on the
      deterioration of hearing loss in otosclerosis patients treated with sodium
      fluoride were included. DATA EXTRACTION: Directness of evidence (DoE) and risk of
      bias (RoB), using the Cochrane Collaboration's tool for assessing risk of bias,
      of the selected articles were assessed. Studies with low DoE, high RoB, or both
      were excluded. Absolute risks, mean deterioration of hearing in decibels, risk
      differences, and their 95% confidence intervals were extracted from the included
      studies. DATA SYNTHESIS: Our search yielded 168 original titles, of which, 2
      placebo-controlled studies were eligible for data extraction. The results of
      these 2 studies were conflicting. One of the included studies, with high DoE and
      moderate RoB, reported an absolute risk reduction for deterioration of hearing
      loss of 18% [95% CI 17; 19] when treating with sodium fluoride. The other
      included study, with high DoE and moderate RoB, reported no clinically
      significant difference in mean deterioration of bone-conduction, air-conduction,
      or air-bone gap between the sodium fluoride group and the placebo group.
      CONCLUSION: There is weak evidence from one study with significant limitations
      that deterioration of hearing loss in otosclerosis patients receiving sodium
      fluoride treatment is less than in patients treated with a placebo.

PMID- 24751747
TI  - Endolymphatic sac surgery for Meniere's disease: a systematic review and meta
      analysis.
AB  - OBJECTIVE: To analyze current endolymphatic surgery techniques and quantify their
      efficacy in controlling vertigo and maintaining hearing in the short and long
      term. DATA SOURCES: A comprehensive literature search using the PubMed-NCBI
      database from 1970 to 2013. STUDY SELECTION: Articles on sac decompression and
      mastoid shunt (with and without silastic) were included. Included studies had to
      report data using the 1985 or 1995 American Academy of Otolaryngology-Head and
      Neck Foundation (AAO-HNS) guidelines, describe surgical technique in detail,
      include a minimum of 10 patients, and have minimum 12 months of follow-up. DATA
      EXTRACTION: Endpoints were vertigo control and hearing preservation using AAO-HNS
      guidelines. Analysis included short-term (>12 mo) and long-term (>24 mo) follow
      up. DATA SYNTHESIS: Data analysis was performed using MedCalc 12.7.0. Each
      article was weighted according to the number of patients treated. Analysis of
      pooled proportion was performed, and Freeman-Tukey transformation was used to
      correct for probable variance. A t test (of proportions) was performed to compare
      differences between groups. CONCLUSION: Endolymphatic sac surgery (sac
      decompression or mastoid shunt) is effective at controlling vertigo in the short
      term (>1 yr of follow-up) and long term (>24 mo) in at least 75% of patients with
      Meniere's disease who have failed medical therapy. Sac decompression and mastoid
      shunting techniques provide similar vertigo control rates. Mastoid shunting, with
      and without silastic, also provides similar vertigo control rates. Non-use of
      silastic, however, seems to maintain stable or improved hearing in more patients
      compared to silastic sheet placement. The data suggest that, once the sac is
      opened, placing silastic does not add benefit and may be deleterious.

PMID- 24751748
TI  - Intraoperative measurement for a new transcutaneous bone conduction hearing
      implant.
AB  - OBJECTIVE: To investigate the possibility of using a modified reverse transfer
      function (RTF) measurement intraoperatively during surgery of a new
      transcutaneous bone conduction hearing implant to evaluate the status of the
      device. METHODS: Tests were performed on a cadaver skull (preclinically) and two
      conductive hearing loss patients implanted with a new transcutaneous bone
      conduction implant. During intraoperative activation, the RTF was measured using
      a microphone attached perpendicularly and directly to the skin in the middle
      section of the forehead. RESULTS: The RTF could be measured for all frequencies
      from 500 to 6, 000 Hz. CONCLUSION: The usage of an intraoperative RTF measurement
      may be a good method to verify the mechanical coupling of the bone conduction
      floating mass transducer and to test the functional integrity of the implant in
      an objective way.

PMID- 24751749
TI  - Tinnitus modulation by stapedectomy.
AB  - OBJECTIVE: To assess change in tinnitus severity after stapedectomy using the
      validated Tinnitus Functional Index (TFI) at 1 and 6 months in 2 cohorts of
      subjects with otosclerosis with different preoperative (TFIpre) distress levels.
      STUDY DESIGN: Prospective within-subjects repeated measures. MATERIALS AND
      METHODS: Twenty-six subjects completed the study between January 2012 and April
      2013. Demographic information, preoperative and postoperative audiometric data at
      1 month, and TFI scores measured preoperatively within 1 month of stapedectomy
      and postoperatively at 1 and 6 months were captured and analyzed. RESULTS:
      Stapedectomy has its largest effect on tinnitus severity reduction within the
      first month of surgery. Cohort A (TFIpre > 15, n = 16) DeltaTFI mean and median
      values were ~20 for the intervals preoperatively to 1 month and preoperatively to
      6 months (p values < 0.01) and dropped to ~0 for the interval between 1 and 6
      months postoperatively. Cohort B (TFIpre < 15, n = 10) DeltaTFI mean and median
      values were ~0 for all time intervals (all pairwise comparison p values > 0.05).
      CONCLUSION: Stapedectomy in patients with otosclerosis with more than a small
      problem with tinnitus (TFIpre > 15) will reduce severity by at least 1 clinical
      category in ~85% of cases within 6 months of surgery. The majority of patients
      will experience stable tinnitus suppression within the first postoperative month.
      In patients with no tinnitus or less than a small problem with tinnitus (TFIpre <
      15), stapedectomy carries a 10% risk of transient worsening of tinnitus at 1
      month, which resolves by the sixth postoperative month.

PMID- 24751750
TI  - Stapedotomy in osteogenesis imperfecta: a prospective study of 32 consecutive
      cases.
AB  - OBJECTIVE: To prospectively evaluate hearing outcomes in patients with
      osteogenesis imperfecta undergoing primary stapes surgery and to isolate
      prognostic factors for success. STUDY DESIGN: A nonrandomized, open, prospective
      case series. SETTING: A tertiary referral center. PATIENTS: Twenty-five
      consecutive patients who underwent 32 primary stapedotomies for osteogenesis
      imperfecta with evidence of stapes fixation and available postoperative pure-tone
      audiometry. INTERVENTION: Primary stapedotomy with vein graft interposition and
      reconstruction with a regular Teflon piston or bucket handle-type piston. MAIN
      OUTCOME MEASURES: Preoperative and postoperative audiometric evaluation using
      conventional 4-frequency (0.5, 1, 2, and 4 kHz) audiometry. Air-conduction
      thresholds, bone-conduction thresholds, and air-bone gap were measured. The
      overall audiometric results as well as the results of audiometric evaluation at 3
      months and at least 1 year after surgery were used. RESULTS: Overall,
      postoperative air-bone gap closure to within 10 dB was achieved in 88% of cases.
      Mean (standard deviation) gain in air-conduction threshold was 22 (9.4) dB for
      the entire case series, and mean (standard deviation) air-bone gap closure was 22
      (9.0) dB. Backward multivariate logistic regression showed that a model with
      preoperative air-bone gap closure and intraoperatively established incus length
      accurately predicts success after primary stapes surgery. CONCLUSION: Stapes
      surgery is a feasible and safe treatment option in patients with osteogenesis
      imperfecta. Success is associated with preoperative air-bone gap and
      intraoperatively established incus length.

PMID- 24751751
TI  - Eustachian tube duplication: a unique anomaly.
AB  - Very few eustachian tube anomalies have been published in the literature and have
      consisted of descriptions of diverticula, hypoplasia/aplasia, fistula, or
      aberrant associated musculature. We present a girl with a novel anomaly
      consisting of a eustachian tube duplication that originates in the nasopharynx
      and exits posterior to a microtic and atretic ear. We review the literature on
      eustachian tube anomalies and also consider the derivation of this anomaly. 

PMID- 24751752
TI  - Anti-inflammatory effects of green soybean extract irradiated with visible light.
AB  - We conducted a preliminary investigation of the effects of visible light
      irradiation on plant extracts, and we observed a strong suppressive effect on
      interleukin (IL) 2 expression with the inhibition of c-Jun amino-terminal kinase
      (JNK) phosphorylation in Jurkat cells by visible light irradiation to ethanol
      extract from green soybeans (LIEGS). This effect was produced only by extracts
      from green soybeans (Glycine max) and not other-color soybeans. LIEGS suppressed
      the lipopolysaccharide-induced IL-6, IL-12 and TNF-alpha expression levels in
      human monocyte THP-1 cells in a concentration-dependent manner. LIEGS was applied
      for 8 weeks to NC/Nga mice. LIEGS suppressed the development of atopic dermatitis
      (AD)-like skin lesions and reduced the dermatitis scores of the mice. The light
      irradiation changed the various types of small-molecule compounds in extracts.
      Visible light irradiation to daidzein with chlorophyll b induced a novel
      oxidative product of daidzein. This product suppressed IL-2 expression in Jurkat
      cells. 

PMID- 24751753
TI  - Rituximab treatment for relapsing minimal change disease and focal segmental
      glomerulosclerosis: a systematic review.
AB  - BACKGROUND: Minimal change disease (MCD) and focal segmental glomerulosclerosis
      (FSGS) remain a therapeutic challenge, since steroids and other immunosuppressive
      agents exhibit an unfavorable adverse event spectrum. The aim of this review was
      to systematically summarize and analyze data from preexisting studies reporting
      the outcome of rituximab (RTX) treatment in these patients. METHODS: Study data
      on adult patients with either steroid-dependent or frequently relapsing MCD/FSGS
      were identified by a PubMed and Embase search. The number of relapses was
      calculated and the use of immunosuppressive co-medication prior to and after RTX
      treatment was quantified. RESULTS: We identified 14 studies including 86 patients
      with frequently relapsing and steroid-dependent MCD or FSGS. Treatment with RTX
      reduced the number of relapses per year from 1.3 (0-9) relapses prior to
      treatment compared to 0 (0-2) after therapy (p < 0.001). Proteinuria decreased
      from 2.43 (0-15) g/day to 0 (0-4.89) g/day (p < 0.001), while serum albumin
      increased from 2.9 (1.2-4.6) at baseline to 4.0 (1.8-5.09) g/l after RTX (p =
      0.001). The use of immunosuppression used at the time of RTX administration was
      also reduced after RTX therapy (p < 0.001). Baseline serum albumin was lower (p =
      0.018), whereas the number of immunosuppressants prior to RTX was higher (p =
      0.018) in patients with relapse after RTX. CONCLUSIONS: The published data
      suggest that RTX is effective in reducing the number of relapses and sparing
      immunosuppression in frequently relapsing and steroid-dependent nephrotic
      syndrome due to MCD and FSGS. These promising findings have to be confirmed in
      controlled and prospective studies.

PMID- 24751755
TI  - Structural variation and interactions among astrocytes of the rostral migratory
      stream and olfactory bulb of the adult rabbit. I. Light microscopic study.
AB  - The organization of the adult rabbit rostral migratory stream (RMS) was studied
      utilizing the rapid-Golgi technique and aniline stains. The RMS consists of a bi
      layered, concentric structure bounding the olfactory ventricle. The inner
      hypercellular layer contains numerous small- to medium-sized cells and is encased
      by the stratum lucidum (SL), a layer of moderate to low cell density. The most
      frequent cell in the SL, here termed an amphomorphic cell (AC), has a mixed
      astrocyte-neuron phenotype. Although each AC exhibits four sets of processes or
      domains, variation in the complexity of these domains justified dividing them
      into six subclasses that might correspond to successive stages of differentiation
      described earlier in rodents. 

PMID- 24751754
TI  - Ischemic skin necrosis caused by glatiramer acetate in multiple sclerosis
      patients.

PMID- 24751756
TI  - Indoleamine 2,3-dioxygenase inhibition alters the non-coding RNA transcriptome
      following renal ischemia-reperfusion injury.
AB  - BACKGROUND: Indoleamine 2,3 dioxygenase (IDO) degrades the essential amino acid
      tryptophan and has been shown to minimize rejection in animal models of renal
      transplantation. Ischemia-reperfusion injury (IRI) is unavoidable in renal
      transplantation and correlates with shorter graft survival times. Despite its
      favorable effects on rejection, there is evidence that IDO may facilitate renal
      IRI. Differentiating the negative impact of IDO on IRI from its pro-tolerant
      effects in allograft rejection is of clinical relevance. In these studies we
      hypothesized that constitutive IDO activity may influence renal genes associated
      with recovery from IRI, and that IDO inhibition may unmask these effects.
      METHODS: We examined the renal transcriptome in a rat model of IRI with and
      without IDO inhibition with 1-methyl-d-tryptophan (1-MT), and assessed for
      alterations in the gene expression signature. RESULTS: These studies demonstrated
      that during recovery from renal IRI, pre-treatment with 1-MT alleviated
      alterations in 105 coding sequences associated with IRI, and in turn triggered
      new changes in 66 non-coding transcripts, the majority of which were represented
      by small nucleolar RNA. CONCLUSION: These results suggest a biologic role for non
      coding, IDO-dependent genes in regulating the early response to IRI.

PMID- 24751758
TI  - Knowing what we do and doing what we should: quality assurance in hemodialysis.
AB  - An international group of around 50 nephrologists and scientists, including
      representatives from large dialysis provider organisations, formulated
      recommendations on how to develop and implement quality assurance measures to
      improve individual hemodialysis patient care, population health and cost
      effectiveness. Discussed were methods thought to be of highest priority, those
      clinical indicators which might be most related to meaningful patient outcomes,
      tools to control treatment delivery and the role of facilitating computerized
      expert systems. Emphasis was given to the use of new technologies such as
      measurement of online dialysance and ways of assessing fluid status. The current
      evidence linking achievement of quality criteria with patient outcomes was
      reviewed. This paper summarizes useful processes and quality measures supporting
      quality assurance that have been agreed across the expert panel. It also notes
      areas where more understanding is required.

PMID- 24751757
TI  - Retinal ganglion cell (RGC) programmed necrosis contributes to ischemia
      reperfusion-induced retinal damage.
AB  - Retinal ischemia-reperfusion (IR) injury remains a common cause of blindness and
      has a final pathway of retinal ganglion cell (RGC) death by apoptosis and
      necrosis. RGC apoptosis was intensively studied in IR injury, while RGC necrosis
      did not receive nearly enough consideration since it was viewed as an accidental
      and unregulated cellular event. However, there is evidence that necrosis, like
      apoptosis, can be implemented by a programmed mechanism. In this study, we tested
      the role of RGC programmed necrosis (necroptosis) in IR-induced retinal injury.
      We employed the mouse model of retinal IR injury for in vivo experiments. The
      oxygen and glucose deprivation (OGD) model was used as an IR model in vitro.
      Primary RGCs were isolated by an immunopanning technique. Necrostatin 1 (Nec1)
      was used to inhibit necroptosis in in vitro and in vivo experiments. The changes
      in gene expression were assessed by quantitative RT-PCR. The distribution of
      proteins in the retina and in RGC cultures was evaluated by immunohistochemistry
      and immunocytochemistry, respectively. Our data suggest that proteins (Ripk1 and
      Ripk3), which initiate necroptosis, were present in normal and ischemic RGCs.
      Treatment with Nec1 significantly reduced retinal damage after IR. Increased RGC
      survival and reduced RGC necrosis following OGD were observed in Nec1-treated
      cultures. We found significantly reduced expression of genes coding pro
      inflammatory markers Il1b, Ccl5, Cxcl10, Nos2 and Cybb in Nec1-treated ischemic
      retinas. Thus, our findings suggest that RGC necroptosis contributes to retinal
      damage after IR through direct loss of cells and induction of associated
      inflammatory responses.

PMID- 24751760
TI  - Rethink your gender attitudes.

PMID- 24751759
TI  - Prevalence of the polycystic ovary syndrome in female residents of Chengdu,
      China.
AB  - BACKGROUND: Polycystic ovary syndrome (PCOS) is one of the most common endocrine
      disorders in women. The data on this syndrome in a Chinese community are limited.
      METHODS: A community-based cross-sectional survey was undertaken. Cluster
      randomized sampling was used. Female residents of Chengdu aged between 12 and 44
      were included according to the constituent ratio of the female population of
      Sichuan province. We used three diagnostic criteria to determine the prevalence:
      the National Institutes of Health diagnostic criteria of PCOS (NIH-1990), the
      revised Rotterdam diagnostic criteria of PCOS (Rott-2003), and the recommended
      diagnostic criteria of PCOS by the Androgen Excess Society (AES-2006). RESULTS:
      1,645 participants were included. The prevalence of PCOS in women aged between 12
      and 44 was 7.1, 11.2 and 7.4%, respectively, according to the three different
      criteria. After the onset of puberty, the prevalence of PCOS increased rapidly
      from 12 to 14 years of age, peaked between 15 and 24 and decreased gradually
      thereafter and reached its lowest point before menopause. CONCLUSIONS: The
      prevalence of PCOS in this study was in the PCOS prevalence range from existing
      studies. According to the trend of prevalence, PCOS might be a temporary
      condition.

PMID- 24751766
TI  - Materials for lasers: All-round perovskites.

PMID- 24751767
TI  - Oxide heterostructures: Thin spin ice under investigation.

PMID- 24751768
TI  - Material witness: Stellar metallurgy.

PMID- 24751769
TI  - Metallic glasses: Fast track to production.

PMID- 24751770
TI  - Bioinspired ceramics: Turning brittleness into toughness.

PMID- 24751771
TI  - Natural materials: Armoured oyster shells.

PMID- 24751772
TI  - Caloric materials near ferroic phase transitions.
AB  - A magnetically, electrically or mechanically responsive material can undergo
      significant thermal changes near a ferroic phase transition when its order
      parameter is modified by the conjugate applied field. The resulting
      magnetocaloric, electrocaloric and mechanocaloric (elastocaloric or barocaloric)
      effects are compared here in terms of history, experimental method, performance
      and prospective cooling applications. 

PMID- 24751773
TI  - Light management for photovoltaics using high-index nanostructures.
AB  - High-performance photovoltaic cells use semiconductors to convert sunlight into
      clean electrical power, and transparent dielectrics or conductive oxides as
      antireflection coatings. A common feature of these materials is their high
      refractive index. Whereas high-index materials in a planar form tend to produce a
      strong, undesired reflection of sunlight, high-index nanostructures afford new
      ways to manipulate light at a subwavelength scale. For example, nanoscale wires,
      particles and voids support strong optical resonances that can enhance and
      effectively control light absorption and scattering processes. As such, they
      provide ideal building blocks for novel, broadband antireflection coatings, light
      trapping layers and super-absorbing films. This Review discusses some of the
      recent developments in the design and implementation of such photonic elements in
      thin-film photovoltaic cells. 

PMID- 24751778
TI  - Crevicular and serum levels of monocyte chemoattractant protein-4 and high
      sensitivity C-reactive protein in periodontal health and disease.
AB  - OBJECTIVES: Chemokines are chemotactic cytokines that are involved in destruction
      of the periodontal structures. The aim of this study is to determine the presence
      of MCP-4 and high sensitivity C reactive protein (hsCRP) levels in gingival
      crevicular fluid (GCF) and serum in periodontal health and disease and to find a
      correlation between MCP-4 and hsCRP in GCF and serum. METHODS: 40 subjects (20
      males and 20 females) were selected and divided into three groups based on
      clinical parameters and radiologic parameters: Group 1 (10 healthy); Group 2 (15
      gingivitis subjects) and Group 3 (15 chronic periodontitis subjects). The levels
      of serum and GCF MCP-4 were determined by ELISA and hsCRP levels were determined
      by immunoturbidimetry method. RESULTS: The mean GCF and serum concentration of
      MCP-4 were the highest for group 3 followed by group 2 and least in group 1.
      Similarly, the mean hsCRP concentrations were highest for group 3 and least in
      group 1. Moreover, a significant positive correlation was found between serum and
      GCF MCP-4 and hsCRP levels and periodontal parameters. CONCLUSION: The levels of
      MCP-4 and hsCRP increased from healthy to periodontitis. It can be proposed that
      MCP-4 and hsCRP are the potential biomarkers of inflammation in periodontal
      health and disease.

PMID- 24751777
TI  - Sub-inhibitory fosmidomycin exposures elicits oxidative stress in Salmonella
      enterica serovar Typhimurium LT2.
AB  - Fosmidomycin is a time-dependent nanomolar inhibitor of methylerythritol
      phosphate (MEP) synthase, which is the enzyme that catalyzes the first committed
      step in the MEP pathway to isoprenoids. Importantly, fosmidomycin is one of only
      a few MEP pathway-specific inhibitors that exhibits antimicrobial activity. Most
      inhibitors identified to date only exhibit activity against isolated pathway
      enzymes. The MEP pathway is the sole route to isoprenoids in many bacteria, yet
      has no human homologs. The development of inhibitors of this pathway holds
      promise as novel antimicrobial agents. Similarly, analyses of the bacterial
      response toward MEP pathway inhibitors provides valuable information toward the
      understanding of how emergent resistance may ultimately develop to this class of
      antibiotics. We have examined the transcriptional response of Salmonella enterica
      serovar typhimurium LT2 to sub-inhibitory concentrations of fosmidomycin via cDNA
      microarray and RT-PCR. Within the regulated genes identified by microarray were a
      number of genes encoding enzymes associated with the mediation of reactive oxygen
      species (ROS). Regulation of a panel of genes implicated in the response of cells
      to oxidative stress (including genes for catalases, superoxide dismutases, and
      alkylhydrogen peroxide reductases) was investigated and mild upregulation in some
      members was observed as a function of fosmidomycin exposure over time. The extent
      of regulation of these genes was similar to that observed for comparable
      exposures to kanamycin, but differed significantly from tetracycline.
      Furthermore, S. typhimurium exposed to sub-inhibitory concentrations of
      fosmidomycin displayed an increased sensitivity to exogenous H2O2 relative to
      either untreated controls or kanamycin-treated cells. Our results suggest that
      endogenous oxidative stress is one consequence of exposures to fosmidomycin,
      likely through the temporal depletion of intracellular isoprenoids themselves,
      rather than other mechanisms that have been proposed to facilitate ROS
      accumulation in bacteria (e.g. cell death processes or the ability of the
      antibiotic to redox cycle). 

PMID- 24751779
TI  - Quantification of tryptase-TIM-3 double-positive mast cells in human chronic
      periodontitis.
AB  - OBJECTIVES: Mast cells (MCs) are implicated in the pathogenesis of allergic
      reactions and inflammatory conditions through the release of inflammatory
      mediators. So far limited attention has been given to the role of MCs in
      periodontitis. T cell immunoglobulin mucin domain (TIM)-3 is an immunomodulatory
      molecule and influences MC function. However, whether TIM-3 is expressed on MCs
      in the process of human periodontal disease has not been reported. Therefore, we
      identified MCs by toluidine blue staining and examined the expression of TIM-3 on
      tryptase-positive MCs in different severities of human chronic periodontitis
      using double-immunofluorescence staining in this study. MATERIAL AND METHODS: A
      total of 83 human periodontal specimens were involved in this study, including
      healthy control tissues (n=25), chronic moderate periodontitis (n=28), and
      chronic severe periodontitis (n=30). The gingival specimens were fixed in 10%
      buffered formalin, stained with haematoxylin and eosin for histopathology, with
      toluidine blue for MCs, and with double-immunofluorescence for identification of
      tryptase-TIM-3 double-positive MCs in gingival tissues. RESULTS: Compared with
      healthy controls, the score of gingival tissue inflammation was significantly
      increased in the chronic moderate periodontitis (P=0.013) and chronic severe
      periodontitis (P<0.0001), and the densities (cells/mm(2)) of tryptase-TIM-3
      double-positive MCs were significantly increased in both the chronic moderate
      (P=0.011) and severe periodontitis groups (P<0.0001). However, compared with the
      chronic moderate periodontitis group, both the score of gingival tissue
      inflammation (P=0.012) and the density of tryptase-TIM-3 double-positive MCs
      (P=0.011) in gingival tissue were significantly increased in the severe
      periodontitis groups. CONCLUSION: Significantly increased number of tryptase-TIM
      3 double-positive MCs had the similar tendency as the severity of periodontitis
      inflammation in human chronic periodontitis. Our data suggest that TIM-3 may have
      a role on MCs in human chronic periodontitis.

PMID- 24751780
TI  - Application of balanced scorecard in the evaluation of a complex health system
      intervention: 12 months post intervention findings from the BHOMA intervention: a
      cluster randomised trial in Zambia.
AB  - INTRODUCTION: In many low income countries, the delivery of quality health
      services is hampered by health system-wide barriers which are often interlinked,
      however empirical evidence on how to assess the level and scope of these barriers
      is scarce. A balanced scorecard is a tool that allows for wider analysis of
      domains that are deemed important in achieving the overall vision of the health
      system. We present the quantitative results of the 12 months follow-up study
      applying the balanced scorecard approach in the BHOMA intervention with the aim
      of demonstrating the utility of the balanced scorecard in evaluating multiple
      building blocks in a trial setting. METHODS: The BHOMA is a cluster randomised
      trial that aims to strengthen the health system in three rural districts in
      Zambia. The intervention aims to improve clinical care quality by implementing
      practical tools that establish clear clinical care standards through intensive
      clinic implementations. This paper reports the findings of the follow-up health
      facility survey that was conducted after 12 months of intervention
      implementation. Comparisons were made between those facilities in the
      intervention and control sites. STATA version 12 was used for analysis. RESULTS:
      The study found significant mean differences between intervention(I) and control
      (C) sites in the following domains: Training domain (Mean I:C; 87.5.vs 61.1, mean
      difference 23.3, p = 0.031), adult clinical observation domain (mean I:C; 73.3
      vs.58.0, mean difference 10.9, p = 0.02 ) and health information domain (mean
      I:C; 63.6 vs.56.1, mean difference 6.8, p = 0.01. There was no gender differences
      in adult service satisfaction. Governance and motivation scores did not differ
      between control and intervention sites. CONCLUSION: This study demonstrates the
      utility of the balanced scorecard in assessing multiple elements of the health
      system. Using system wide approaches and triangulating data collection methods
      seems to be key to successful evaluation of such complex health intervention.
      TRIAL NUMBER: ClinicalTrials.gov NCT01942278.

PMID- 24751781
TI  - Structural morphology, upconversion luminescence and optical thermometric sensing
      behavior of Y2O3:Er(3+)/Yb(3+) nano-crystalline phosphor.
AB  - Infrared-to-visible upconverting rare earths Er(3+)/Yb(3+) co-doped Y2O3 nano
      crystalline phosphor samples have been prepared by solution combustion method
      followed by post-heat treatment at higher temperatures. A slight increase in
      average crystallite size has been found on calcinations verified by X-ray
      analysis. Transmission electron microscopy (TEM) confirms the nano-crystalline
      nature of the as-prepared and calcinated samples. Fourier transform infrared
      (FTIR) analysis shows the structural changes in as-prepared and calcinated
      samples. Upconversion and downconversion emission recorded using 976 and 532 nm
      laser sources clearly demonstrates a better luminescence properties in the
      calcinated samples as compared to as-prepared sample. Upconversion emission has
      been quantified in terms of standard chromaticity diagram (CIE) showing a shift
      in overall upconversion emission of as-prepared and calcinated samples.
      Temperature sensing behaviour of this material has also been investigated by
      measurement of fluorescence intensity ratio (FIR) of various signals in green
      emission in the temperature range of 315 to 555 K under 976 nm laser excitation.

PMID- 24751782
TI  - Photophysical aspects of biological photosensitizer Kynurenic acid from the
      perspective of experimental and quantum chemical study.
AB  - In the present contribution, we have explored ground and excited state
      spectroscopic properties of an antiexcitotoxic and anticonvulsant drug, Kynurenic
      acid (KA), through steady-state absorption, emission and time-resolved emission
      spectroscopy and quantum chemical calculations. The main focus of this article is
      to illustrate the effects of various parameters such as the nature of the
      solvents and pH of the medium on the spectral properties of KA which confirms the
      presence of different neutral and ionic species in the ground and excited states.
      The molecule KA exists mainly as keto- or anionic form in the ground state,
      whereas the main contribution of its emission is arising from the keto tautomer
      in the excited state. Quantum chemical calculations by Density Functional Theory
      (DFT) method has been effectively employed to correlate the experimental
      findings. The ground and excited state properties of KA ascertained by means of
      experimental and theoretical method reveal that it resembles well with other two
      compounds, 4-hydroxyquinoline and xanthurenic acid formed by the decomposition of
      UV filters. 

PMID- 24751783
TI  - The variable hinge region of novel PKCs determines localization to distinct
      regions of the immunological synapse.
AB  - The immunological synapse (IS) formed between a T cell and its cognate antigen
      presenting cell (APC) enables the directional secretion of cytolytic and
      inflammatory molecules. Synaptic architecture is established in part by a two
      step cascade of novel protein kinase C (nPKC) isozymes. PKCepsilon and PKCeta
      arrive at the IS first, and occupy the entire synaptic membrane. Then, PKCtheta
      accumulates in a smaller zone at the center of the contact. We investigated the
      molecular basis for this differential recruitment behavior using chimeric nPKC
      constructs and total internal reflection fluorescence microscopy. Our studies
      revealed that the V3 linker just N-terminal to the kinase domain plays a crucial
      role in specifying nPKC localization. Substitution of this linker switched the
      scope and the kinetics of PKCtheta accumulation to that of PKCepsilon and PKCeta,
      and vice versa. Although the V3 was necessary for synaptic compartmentalization,
      it was not sufficient, as the tandem C1 domains were also required to mediate
      membrane association. Together, these results suggest a model whereby the V3
      linker controls nPKC sub-compartmentalization after initial C1 domain-mediated
      accumulation at the IS. 

PMID- 24751784
TI  - Separation of mAbs molecular variants by analytical hydrophobic interaction
      chromatography HPLC: overview and applications.
AB  - Hydrophobic interaction chromatography-high performance liquid chromatography
      (HIC-HPLC) is a powerful analytical method used for the separation of molecular
      variants of therapeutic proteins. The method has been employed for monitoring
      various post-translational modifications, including proteolytic fragments and
      domain misfolding in etanercept (Enbrel(r)); tryptophan oxidation, aspartic acid
      isomerization, the formation of cyclic imide, and alpha amidated carboxy terminus
      in recombinant therapeutic monoclonal antibodies; and carboxy terminal
      heterogeneity and serine fucosylation in Fc and Fab fragments. HIC-HPLC is also a
      powerful analytical technique for the analysis of antibody-drug conjugates. Most
      current analytical columns, methods, and applications are described, and critical
      method parameters and suitability for operation in regulated environment are
      discussed, in this review.

PMID- 24751785
TI  - Public health in times of austerity.

PMID- 24751786
TI  - Use of Rotterdam CT scores for mortality risk stratification in children with
      traumatic brain injury.
AB  - OBJECTIVES: The Rotterdam CT score refined features of the Marshall score and was
      designed to categorize traumatic brain injury type and severity in adults. The
      objective of this study was to determine whether the Rotterdam CT score can be
      used for mortality risk stratification after pediatric traumatic brain injury.
      DESIGN: In children with moderate to severe traumatic brain injury, a comparison
      of observed versus predicted mortality was calculated using published model
      probabilities of adult mortality. Development and validation of a new pediatric
      mortality model using randomly selected prediction and validation samples from
      our cohort. SETTING: A single level 1 pediatric trauma center. SUBJECTS: Six
      hundred thirty-two children with moderate or severe traumatic brain injury.
      INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Sixteen percent of the
      patients (101 of 632) died prior to hospital discharge. The predicted mortality
      based on Rotterdam score for adults with moderate or severe traumatic brain
      injury discriminated pediatric observed mortality well (area under the curve =
      0.85; 95% CI, 0.80-0.89) but had poor calibration, overestimating or
      underestimating mortality for children in several Rotterdam categories. A
      predictive model based on children with moderate or severe traumatic brain injury
      from the single center discriminated mortality well (area under the curve, 0.80;
      95% CI, 0.68-0.91) and showed good calibration and overall fit. CONCLUSIONS:
      Children with traumatic brain injury have better survival than adults in
      Rotterdam CT score categories representing less severe injuries but worse
      survival than adults in higher score categories. A novel, validated pediatric
      mortality model based on the Rotterdam score is accurate in children with
      moderate or severe traumatic brain injury and can be used for risk
      stratification.

PMID- 24751787
TI  - Alteplase infusion versus dwell for clearance of partially occluded central
      venous catheters in critically ill pediatric patients.
AB  - OBJECTIVE: To evaluate the efficacy and safety of alteplase infusions and
      alteplase local instillations (dwells) to clear partially occluded central venous
      catheters in critically ill children. DESIGN: Retrospective study. SETTING: PICU
      in a single, tertiary care, academic children's hospital. PATIENTS: Retrospective
      review of the medical records of all critically ill pediatric patients less than
      18 years old who received an alteplase infusion or dwell as the treatment for a
      partial central venous catheter occlusion. The typical infusion regimen was to
      administer 0.1 mg/kg of body weight (maximum, 2 mg/dose) of alteplase in 25 mL of
      0.9% sodium chloride over 3 hours. The standard dwell was to administer and
      aspirate alteplase in a 1 mg/mL concentration as a fixed dose as ordered by the
      prescriber (maximum, 2 mg/dose). Efficacy was defined as documentation of
      positive blood return from the catheter. Radiology reports, nursing and physician
      documentation, and laboratory values were reviewed to assess for bleeding events.
      INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: One hundred fifty occlusion
      events were included for analysis. Overall, 72 of 84 alteplase infusions (86%)
      and 53 of 66 alteplase dwells (80%) resulted in resolution of the lumen occlusion
      event as documented by positive blood return from the catheter after a maximum of
      two doses (p = 0.39). One major bleeding event occurred in each arm; both were
      deemed unlikely related to alteplase. CONCLUSIONS: Alteplase infusions to clear
      partially occluded central venous catheters appear to be as efficacious as
      alteplase dwells in critically ill children. In occlusions treated with an
      infusion, more occlusions resolved in older and larger patients and in patients
      with catheters in place less than 7 days. In occlusions treated with a dwell,
      more occlusions resolved in smaller catheters. The safety profile for both
      infusions and dwells was acceptable for the pediatric critically ill population.

PMID- 24751789
TI  - Adrenaline, terlipressin, and corticoids versus adrenaline in the treatment of
      experimental pediatric asphyxial cardiac arrest.
AB  - OBJECTIVE: To analyze if treatment with adrenaline (epinephrine) plus
      terlipressin plus corticoids achieves higher return of spontaneous circulation
      than adrenaline in an experimental infant animal model of asphyxial cardiac
      arrest. DESIGN: Prospective randomized animal study. SETTING: Experimental
      department in a University Hospital. SUBJECTS: Forty-nine piglets were studied.
      INTERVENTIONS: Cardiac arrest was induced by at least 10 minutes of removal of
      mechanical ventilation and was followed by manual external chest compressions and
      mechanical ventilation. After 3 minutes of resuscitation, piglets that did not
      achieve return of spontaneous circulation were randomized to two groups:
      adrenaline 0.02 mg kg every 3 minutes (20 animals) and adrenaline 0.02 mg kg
      every 3 minutes plus terlipressin 20 MUg kg every 6 minutes plus hydrocortisone
      30 mg kg one dose (22 animals). Resuscitation was discontinued when return of
      spontaneous circulation was achieved or after 24 minutes. MEASUREMENT AND MAIN
      RESULTS: Return of spontaneous circulation was achieved in 14 piglets (28.5%),
      14.2% with only cardiac massage and ventilation. Return of spontaneous
      circulation was achieved in 25% of piglets treated with adrenaline and in 9.1% of
      those treated with adrenaline plus terlipressin plus hydrocortisone (p = 0.167).
      Return of spontaneous circulation was achieved in 45.4% of animals with pulseless
      electric activity, 20% with asystole, and 0% with ventricular fibrillation (p =
      0.037). Shorter duration of cardiac arrest, higher mean blood pressure and EtCO2
      and lower PaCO2 before resuscitation, and higher mean blood pressure during
      resuscitation were associated with higher return of spontaneous circulation.
      CONCLUSIONS: Treatment with adrenaline plus terlipressin plus corticoids does not
      achieve higher return of spontaneous circulation than that with adrenaline in an
      infant animal model of asphyxial cardiac arrest.

PMID- 24751788
TI  - Continuous infusion of clonidine in ventilated newborns and infants: a randomized
      controlled trial.
AB  - OBJECTIVES: To assess the influence of an infusion of clonidine 1 MUg/kg/hr on
      fentanyl and midazolam requirement in ventilated newborns and infants. DESIGN:
      Prospective, double-blind, randomized controlled multicenter trial. Controlled
      trials.com/ISRCTN77772144. SETTING: Twenty-eight level 3 German PICUs/neonatal
      ICUs. PATIENTS: Ventilated newborns and infants: stratum I (1-28 d), stratum II,
      (29-120 d), and stratum III (121 d to 2 yr). INTERVENTIONS: Patients received
      clonidine 1 MUg/kg/hr or placebo on day 4 after intubation. Fentanyl and
      midazolam were adjusted to achieve a defined level of analgesia and sedation
      according to Hartwig score. MEASUREMENTS AND MAIN RESULTS: Two hundred nineteen
      infants were randomized; 212 received study medication, 69.7% were ventilated in
      the postoperative care and 30.3% for other reasons. Primary endpoint: consumption
      of fentanyl and midazolam in the 72 hours following the onset of study medication
      (main observation period) in the overall study population. The confirmatory
      analysis of the overall population showed no difference in the consumption of
      fentanyl and midazolam. Explorative age-stratified analysis demonstrated that in
      stratum I (n = 112) the clonidine group had a significantly lower consumption of
      fentanyl (clonidine: 2.1 +/- 1.8 MUg/kg/hr, placebo: 3.2 +/- 3.1 MUg/kg/hr; p =
      0.032) and midazolam (clonidine: 113.0 +/- 100.1 MUg/kg/hr, placebo: 180.2 +/-
      204.0 MUg/kg/hr; p = 0.030). Strata II (n = 43) and III (n = 46) showed no
      statistical difference. Sedation and withdrawal-scores were significantly lower
      in the clonidine group of stratum I (p < 0.001). Frequency of severe adverse
      events did not differ between groups. CONCLUSIONS: Clonidine 1 MUg/kg/hr in
      ventilated newborns reduced fentanyl and midazolam demand with deeper levels of
      analgesia and sedation without substantial side effects. This was not
      demonstrated in older infants, possibly due to lower clonidine serum levels.

PMID- 24751790
TI  - Understanding the global epidemiology of pediatric critical illness: the power,
      pitfalls, and practicalities of point prevalence studies.
AB  - OBJECTIVE: The point prevalence methodology is a valuable epidemiological study
      design that can optimize patient enrollment, prospectively gather individual
      level data, and measure practice variability across a large number of geographic
      regions and healthcare settings. The objective of this article is to review the
      design, implementation, and analysis of recent point prevalence studies
      investigating the global epidemiology of pediatric critical illness. DATA
      SOURCES: Literature review and primary datasets. STUDY SELECTION: Multicenter,
      international point prevalence studies performed in PICUs since 2007. DATA
      EXTRACTION: Study topic, number of sites, number of study days, patients
      screened, prevalence of disease, use of specified therapies, and outcomes. DATA
      SYNTHESIS: Since 2007, five-point prevalence studies have been performed on acute
      lung injury, neurologic disease, thromboprophylaxis, fluid resuscitation, and
      sepsis in PICUs. These studies were performed in 59-120 sites in 7-28 countries.
      All studies accounted for seasonal variation in pediatric disease by collecting
      data over multiple study days. Studies screened up to 6,317 patients and reported
      data on prevalence and therapeutic variability. Three studies also reported short
      term outcomes, a valuable but atypical data element in point prevalence studies.
      Using these five studies as examples, the advantages and disadvantages and
      approach to designing, implementing, and analyzing point prevalence studies are
      reviewed. CONCLUSIONS: Point prevalence studies in pediatric critical care can
      efficiently provide valuable insight on the global epidemiology of disease and
      practice patterns for critically ill children.

PMID- 24751792
TI  - Sepsis in obstetrics: cause, prevention, and treatment.
AB  - PURPOSE OF REVIEW: The aim of the study was to provide a summary of recent
      guidance on sepsis in obstetrics. RECENT FINDINGS: Morbidity and mortality from
      sepsis is increasing in the UK and other developed countries. In many cases, care
      has been found to be substandard. Common themes are a failure to recognize and
      respond to the sick woman and inadequate antibiotic and fluid management in the
      septic parturient. SUMMARY: Increased awareness of obstetric sepsis is required.
      Women and their families need to be informed about it and staff must have the
      skills and competencies to recognize this early. The management of severe sepsis
      in obstetrics is multidisciplinary. Implementation of the goals of the Surviving
      Sepsis Campaign into obstetric practice is important to improve outcomes. More
      research is needed to validate the parameters used in this and early warning
      scores for the obstetric population.

PMID- 24751791
TI  - Time for a neonatal-specific consensus definition for sepsis.
AB  - OBJECTIVE: To review the accuracy of the pediatric consensus definition of sepsis
      in term neonates and to determine the definition of neonatal sepsis used. STUDY
      SELECTION: The review focused primarily on pediatric literature relevant to the
      topic of interest. CONCLUSIONS: Neonatal sepsis is variably defined based on a
      number of clinical and laboratory criteria that make the study of this common and
      devastating condition very difficult. Diagnostic challenges and uncertain disease
      epidemiology necessarily result from a variable definition of disease. In 2005,
      intensivists caring for children recognized that as new drugs became available,
      children would be increasingly studied and thus, pediatric-specific consensus
      definitions were needed. Pediatric sepsis criteria are not accurate for term
      neonates and have not been examined in preterm neonates for whom the
      developmental stage influences aberrations associated with host immune response.
      Thus, specific consensus definitions for both term and preterm neonates are
      needed. Such definitions are critical for the interpretation of observational
      studies, future training of scientists and practitioners, and implementation of
      clinical trials in neonates.

PMID- 24751793
TI  - Wide early ulceration of a livedoid infantile hemangioma of the gluteal area.

PMID- 24751794
TI  - Soluble ST2 and interleukin-33 levels in coronary artery disease: relation to
      disease activity and adverse outcome.
AB  - OBJECTIVES: ST2 is a receptor for interleukin (IL)-33. We investigated an
      association of soluble ST2 (sST2) and IL-33 serum levels with different clinical
      stages of coronary artery disease. We assessed the predictive value of sST2 and
      IL-33 in patients with stable angina, non-ST elevation myocardial infarction
      (NSTEMI) and ST elevation myocardial infarction (STEMI). METHODS: We included 373
      patients of whom 178 had stable angina, 97 had NSTEMI, and 98 had STEMI. Patients
      were followed for a mean of 43 months. The control group consisted of 65
      individuals without significant stenosis on coronary angiography. Serum levels of
      sST2 and IL-33 were measured by ELISAs. RESULTS: sST2 levels were significantly
      increased in patients with STEMI as compared to patients with NSTEMI and stable
      angina as well as with controls. IL-33 levels did not differ between the four
      groups. During follow-up, 37 (10%) patients died and the combined endpoint (all
      cause death, MI and rehospitalisation for cardiac causes) occurred in 66 (17.6%)
      patients. sST2 serum levels significantly predicted mortality in the total
      cohort. When patients were stratified according to their clinical presentation,
      the highest quintile of sST2 significantly predicted mortality in patients with
      STEMI, but not with NSTEMI or stable coronary artery disease. sST2 was a
      significant predictor for the combined endpoint in STEMI patients and in patients
      with stable angina. Serum levels of IL-33 were not associated with clinical
      outcome in the total cohort, but the highest quintile of IL-33 predicted
      mortality in patients with STEMI. CONCLUSIONS: Serum levels of sST2 are increased
      in patients with acute coronary syndromes as compared to levels in patients with
      stable coronary artery disease and in individuals without coronary artery
      disease. sST2 and IL-33 were associated with mortality in patients with STEMI but
      not in patients with NSTEMI or stable angina.

PMID- 24751795
TI  - Viability of long-term gene therapy in the cochlea.
AB  - Gene therapy has been investigated as a way to introduce a variety of genes to
      treat neurological disorders. An important clinical consideration is its long
      term effectiveness. This research aims to study the long-term expression and
      effectiveness of gene therapy in promoting spiral ganglion neuron survival after
      deafness. Adenoviral vectors modified to express brain derived neurotrophic
      factor or neurotrophin-3 were unilaterally injected into the guinea pig cochlea
      one week post ototoxic deafening. After six months, persistence of gene
      expression and significantly greater neuronal survival in neurotrophin-treated
      cochleae compared to the contralateral cochleae were observed. The long-term gene
      expression observed indicates that gene therapy is potentially viable; however
      the degeneration of the transduced cells as a result of the original ototoxic
      insult may limit clinical effectiveness. With further research aimed at
      transducing stable cochlear cells, gene therapy may be an efficacious way to
      introduce neurotrophins to promote neuronal survival after hearing loss. 

PMID- 24751797
TI  - Co-infections, inflammation and oncogenesis: future directions for EBV research.
AB  - Epstein-Barr virus (EBV) is aetiologically linked to a wide range of human
      tumours. Some arise as accidents of the virus' lifestyle in its natural niche,
      the B lymphoid system; these include B-lymphoproliferative disease of the
      immunocompromised, Hodgkin Lymphoma, Burkitt Lymphoma and particular forms of
      diffuse large B cell lymphoma. Interestingly, HIV infection increases the
      incidence of each of these B cell malignancies, though by different degrees and
      for different reasons. Other EBV-associated tumours arise through rare viral
      entry into unnatural target tissues; these include all cases of nasal T/NK cell
      lymphoma and of undifferentiated nasopharyngeal carcinoma plus a small but
      significant subset of gastric carcinomas, a tumour type more generally associated
      with chronic Helicobacter pylori infection. Understanding EBV's involvement in
      the pathogenesis of these different malignancies is an important long-term goal.
      This article focuses on two overlapping, but relatively neglected, areas of
      research that could contribute to that goal. The first addresses the mechanisms
      whereby coincident infections with other pathogens increase the risk of EBV
      positive malignancies, and takes as its paradigm the actions of holoendemic
      malaria and HIV infections as co-factors in Burkitt lymphomagenesis. The second
      widens the argument to include both infectious and non-infectious sources of
      chronic inflammation in the pathogenesis of EBV-positive tumours such as T/NK
      cell lymphoma, nasopharyngeal carcinoma and gastric carcinoma. 

PMID- 24751796
TI  - Prevalence of cognitive impairment no dementia in a rural area of Northern China.
AB  - OBJECTIVE: Few data are available on the prevalence of cognitive impairment no
      dementia (CIND) in rural China. The aim of this study was to estimate the
      prevalence of CIND in individuals aged 60 years and older in a large rural
      community, and to analyze the associated risk factors. METHODS: A two-phase, door
      to-door epidemiological study was used for residents aged 60 years and older in
      Ji County, a rural county near Tianjin in Northern China. In phase 1 of the
      study, the Mini-Mental State Examination and Clinical Dementia Rating were
      administered for screening purposes. In phase 2, the subjects who screened
      positive were further examined by neurologists. A total of 5,744 individuals
      underwent the home visit interview, where demographic variables and comorbidities
      were recorded; 5,550 individuals completed the two phases. CIND was diagnosed by
      the Aging, Demographics and Memory Study on CIND criteria. The odds ratio (OR)
      for each risk factor was calculated by logistic regression analysis. RESULTS: The
      prevalence of CIND among those aged 60 years and older was 23.3%. The prevalence
      of CIND was lower among those with a higher level of education or social
      involvement. CIND was more prevalent in females, older individuals, those with a
      past history of stroke, and those living without a partner. Significant risk
      factors were found by multivariate analyses: past history of stroke (OR = 1.889;
      95% CI: 1.437-2.483); being female (OR = 1.546; 95% CI: 1.305-1.832); and having
      no partner (divorced, widowed or single; OR = 1.250; 95% CI: 1.042-1.499). In
      turn, level of education (OR = 0.560; 95% CI: 0.460-0.681) and engagement in
      social activities (OR = 0.339; 95% CI: 0.258-0.404) were protective factors.
      CONCLUSIONS: This is the first large-scale community-based epidemiological study
      assessing the prevalence of cognitive loss in the rural Chinese population. The
      total prevalence of CIND observed was 23.3%, which was higher than in other
      studies in Western and Asian countries. Living without a partner, female gender
      and previous stroke increased the risk of CIND, whereas a higher level of
      education and engagement in social activities reduced the risk of CIND.

PMID- 24751798
TI  - Characterization of complete genome and small RNA profile of pagoda yellow mosaic
      associated virus, a novel badnavirus in China.
AB  - A new badnavirus was discovered from pagoda trees showing yellow mosaic symptoms
      on the leaves by high throughput sequencing of small RNAs. The complete genome of
      this virus was determined to comprise 7424 nucleotides, and the virus shared 40.4
      45.1% identity with that of other badnaviruses. The genome encodes five open
      reading frames (ORFs) on the plus strand, which includes three conserved
      badnaviral ORFs. These results suggest that this virus is a new member of the
      genus Badnavirus in the family Caulimoviridae. The virus is tentatively named
      pagoda yellow mosaic associated virus (PYMAV). Phylogenetic analysis suggested
      that this virus together with gooseberry vein banding virus (GVBV) and grapevine
      vein-clearing virus (GVCV) forms a separate group that is distinct two other well
      characterized badnaviral groups. Additionally, the viral derived small RNA
      (vsRNA) profile of PYMAV was analyzed and compared with that of viruses within
      the same family. Results showed that the most abundant PYMAV vsRNAs were 21-nt,
      whereas other viruses in the same family have a predominance of 22- or 24-nt
      vsRNA. The percentage of sense PYMAV vsRNA was almost equal to that of antisense
      vsRNA, whereas vsRNAs of other viruses in the family display preferences toward
      the sense strand of their genome. Furthermore, PYMAV vsRNAs were symmetrically
      distributed along the genome with no obvious vsRNA generating hotspots.

PMID- 24751799
TI  - Novel recombinant GII.P16_GII.13 and GII.P16_GII.3 norovirus strains in Italy.
AB  - Novel norovirus strains are continuously emerging worldwide. Molecular
      investigation and phylogenetic analysis identified GII.P16 recombinant
      noroviruses from the stools of four Italian children with gastroenteritis. The
      capsid gene was characterized as either GII.13 or GII.3. The GII.P16_GII.13
      Italian strains were closely related to German strains involved in a large
      outbreak in the second half of 2012 and the Italian strains are the first
      recorded occurrence of GII.P16_GII.13 in Europe.

PMID- 24751800
TI  - Multiple sclerosis: insights into pathophysiology and novel therapeutic avenues.

PMID- 24751801
TI  - Proteomics and pathway analysis of N-glycosylated mammary gland proteins in
      response to Escherichia coli mastitis in cattle.
AB  - The aim of this study was to investigate the N-linked glycosylated protein
      profile of mammary tissue from healthy cows and cows with mastitis due to
      Escherichia coli, in order to understand the molecular mechanisms of the host
      response to mastitis. N-glycopeptides were enriched with a lectin mixture and
      identified through high-accuracy mass spectrometry. A total of 551 N
      glycosylation sites, corresponding to 294 proteins, were identified in the
      mammary tissues of healthy cows; these glycoproteins were categorised into three
      functional groups and clustered into 11 specific pathways. A total of 511 N
      glycosylation sites, corresponding to 283 glycosylated proteins, were detected in
      the mammary tissues of cows with E. coli mastitis. There were differences in N
      glycosylation sites in 98 proteins in the mammary tissues of healthy cows and
      cows with mastitis due to E. coli. Most proteins with altered glycosylation were
      those involved in responses to stress, cell adhesion and the immune response, and
      were assigned to five specific pathways based on their gene ontology annotation.
      The results from this study show that the glycosylated protein profile in the
      mammary tissues of healthy and mastitic cows are different, and altered
      glycoproteins are associated with several pathways, including the lysosome and O
      glycan biosynthesis pathways.

PMID- 24751802
TI  - Chemotherapy: life gained, years lost?

PMID- 24751804
TI  - Therapeutic benefits in atopic dermatitis care from the patients' perspective:
      results of the German national health care study 'Atopic Health'.
AB  - BACKGROUND/AIMS: Numerous therapies are recommended to treat atopic dermatitis.
      The German national health care study 'Atopic Health' generated nationwide data
      on the care situation from the patients' perspective. METHODS: Data for 1,678
      adult patients were collected within a retrospective cohort study throughout the
      year 2010. Six scores to capture satisfaction with care, quality of life
      (Dermatology Life Quality Index, EQ-5D-VAS), therapeutic success and benefits
      (Patient Benefit Index) were analyzed using descriptive methods and analysis of
      variance. RESULTS: 82.1% of patients were highly satisfied with their treatment.
      Topical corticosteroids and climate therapies were associated with the best
      success ratings. Quality of life was moderately impaired (mean Dermatology Life
      Quality Index 8.5 +/- 6.5). 88.4% of the patients indicated a relevant
      therapeutic benefit (Patient Benefit Index >= 1) with significantly better scores
      for topical immunomodulating therapies and climate therapies. CONCLUSION: The
      most frequently applied therapies presented pleasant success and benefit ratings,
      even if quality of life could be improved for more than one third of patients.

PMID- 24751805
TI  - A predictive diagnostic imaging calculator as a clinical decision support tool.

PMID- 24751803
TI  - Can we deliver randomized trials of focal therapy in prostate cancer?
AB  - Tissue-preserving focal therapies, such as brachytherapy, cryotherapy, high
      intensity focused ultrasound and photodynamic therapy, aim to target individual
      cancer lesions rather than the whole prostate. These treatments have emerged as
      potential interventions for localized prostate cancer to reduce treatment-related
      adverse-effects associated with whole-gland treatments, such as radical
      prostatectomy and radiotherapy. In this article, the Prostate Cancer RCT
      Consensus Group propose that a novel cohort-embedded randomized controlled trial
      (RCT) would provide a means to study men with clinically significant localized
      disease, which we defined on the basis of PSA level (<= 15 ng/ml or <= 20 ng/ml),
      Gleason grade (Gleason pattern <= 4 + 4 or <= 4 + 3) and stage (<= cT2cN0M0).
      This RCT should recruit men who stand to benefit from treatment, with the control
      arm being whole-gland surgery or radiotherapy. Composite outcomes measuring rates
      of local and systemic salvage therapies at 3-5 years might best constitute the
      basis of the primary outcome on which to change practice.

PMID- 24751807
TI  - Sudden death in incident dialysis patients.
AB  - BACKGROUND: Sudden death (SD) constitutes one of the principal causes of death
      and is an important problem in healthcare provision. Cardiovascular diseases have
      a high prevalence in dialysis patients and constitute the principal cause of
      death. We sought to analyze retrospectively the incidence of SD in patients
      commencing dialysis and the factors related to its presence. METHODS: We
      evaluated all the patients who began dialysis in our center between 1/11/2003 and
      15/9/2007, and who were followed up until death, transplant, or study completion
      on 31/12/2012. We determined the presence of SD according to the following
      criteria: SD at 24 h (SD 24H): unexpected death occurring in the 24 h following
      the start of symptoms, or when the patient was found dead and had been seen alive
      24 h earlier; SD at 1 h (SD 1H): death witnessed as occurring in the first hour
      following the start of symptoms. RESULTS: We evaluated 285 patients, mean age
      65.67 +/- 15.7 years. In a follow-up of 39.9 +/- 34.2 months (947.6 patient-years
      of follow-up) 168 died (59%), 28 (10%) patients presented SD 24H (2.9/100 patient
      years), and 16 (6%) patients presented SD 1H (1.7/100 patient-years). In the
      multivariate analysis, having had a myocardial infarction or having had
      electrocardiographic abnormalities (Q wave, negative T wave, subendocardial
      lesion or QRS >120 ms) were the principal independent predictors of SD 24H (OR
      7.83; 95% CI 2.20-27.86; p = 0.001) and of SD 1H (OR 13.43; 95% CI 1.56-115.42; p
      = 0.018). CONCLUSIONS: SD on dialysis is very frequent. Two groups can be
      identified easily, with risk profiles clearly differentiated.

PMID- 24751806
TI  - Loss of PINK1 impairs stress-induced autophagy and cell survival.
AB  - The mitochondrial kinase PINK1 and the ubiquitin ligase Parkin are participating
      in quality control after CCCP- or ROS-induced mitochondrial damage, and their
      dysfunction is associated with the development and progression of Parkinson's
      disease. Furthermore, PINK1 expression is also induced by starvation indicating
      an additional role for PINK1 in stress response. Therefore, the effects of PINK1
      deficiency on the autophago-lysosomal pathway during stress were investigated.
      Under trophic deprivation SH-SY5Y cells with stable PINK1 knockdown showed
      downregulation of key autophagic genes, including Beclin, LC3 and LAMP-2. In good
      agreement, protein levels of LC3-II and LAMP-2 but not of LAMP-1 were reduced in
      different cell model systems with PINK1 knockdown or knockout after addition of
      different stressors. This downregulation of autophagic factors caused increased
      apoptosis, which could be rescued by overexpression of LC3 or PINK1. Taken
      together, the PINK1-mediated reduction of autophagic key factors during stress
      resulted in increased cell death, thus defining an additional pathway that could
      contribute to the progression of Parkinson's disease in patients with PINK1
      mutations. 

PMID- 24751808
TI  - Monitoring of oesophageal pressure.
AB  - PURPOSE OF REVIEW: Studies in patients with acute respiratory distress syndrome
      (ARDS) have been unable to demonstrate a survival advantage with higher levels of
      positive end-expiratory pressure (PEEP) to open atelectatic lung regions or
      prevent their cyclic collapse. This review will discuss the challenges of
      accurately measuring pleural pressure with balloon-tipped catheters in the
      oesophagus, and the utility of such pressure monitoring to set PEEP and assess
      lung mechanics, focusing on patients with ARDS. RECENT FINDINGS: Recent
      investigations have suggested that the monitoring of oesophageal pressure in ARDS
      patients may help individualize PEEP settings to optimize lung recruitment based
      on transpulmonary pressure. SUMMARY: Changes in oesophageal pressure likely
      accurately reflect global changes in pleural pressure in supine patients with
      ARDS. However, absolute oesophageal pressure values in such patients may be
      subject to local artefacts and may substantially overestimate pleural pressure in
      other lung regions. Setting PEEP high enough to achieve a targeted end-expiratory
      transpulmonary pressure in the region of the oesophageal balloon catheter could
      overdistend other lung regions. Measurement of oesophageal pressure is feasible,
      but its clinical utility to titrate PEEP, compared with routine assessment,
      awaits experimental confirmation.

PMID- 24751809
TI  - Current tools for assessing heart function and perfusion adequacy.
AB  - PURPOSE OF REVIEW: Many devices are currently available for measuring cardiac
      output and function. Understanding the utility of these devices requires an
      understanding of the determinants of cardiac output and cardiac function, and the
      use of these parameters in the management of critically ill patients. This review
      stresses the meaning of the physiological measures that are obtained with these
      devices and how these values can be used. RECENT FINDINGS: Evaluation of devices
      for haemodynamic monitoring can include just measurement of cardiac output, the
      potential to track spontaneous changes in cardiac output or changes produced by
      volume infusions or vasoactive drugs, or the ability to assess cardiac function.
      Each of these puts different demands on the need for accuracy, precision, and
      reliability of the devices, and thus devices must be evaluated based on the
      clinical need. SUMMARY: Evaluation of cardiac function is useful when first
      dealing with an unstable patient, but for ongoing management measurement of
      cardiac output itself is key and even more so the trend in relationship to the
      patient's overall condition. This evaluation would be greatly benefited by the
      addition of objective measures of tissue perfusion.

PMID- 24751810
TI  - Post-conditioning to improve cardiopulmonary resuscitation.
AB  - PURPOSE OF REVIEW: Despite decades of advances in prehospital and in-hospital
      medical care, patients with out-of-hospital cardiac arrest continue to have poor
      neurologic and cardiac function following otherwise successful resuscitation.
      This review examines the mechanisms and therapeutic strategies currently under
      development to activate the post-conditioning pathways and thereby improve
      survival and function. RECENT FINDINGS: Post-conditioning utilizes the
      reperfusion injury salvage kinase (RISK) and survivor activating factor
      enhancement (SAFE) pathways as common avenues to promote cell survival and
      function. Ischemic post-conditioning and multiple medications activate these
      pathways resulting in improved cardiac and neurological function in animal models
      of cardiac arrest. SUMMARY: Detailed knowledge of the RISK and SAFE pathways can
      be used for further drug development. Human studies are now underway to test some
      of these strategies, but further clinical trials are necessary to translate these
      therapies to clinical practice.

PMID- 24751811
TI  - Sclerosing cavernous hemangioma of the cavernous sinus mimicking congenital
      fibrosis of the extraocular muscles.
AB  - A girl with a clinical presentation suggestive of unilateral congenital fibrosis
      of the extraocular muscles type 3 at 2 years of age years later developed
      progressive ophthalmoplegia and an afferent pupillary defect. Reimaging revealed
      a lesion diagnosed as a sclerosing cavernous sinus hemangioma with focal
      calcification. Cavernous sinus hemangioma is a rare, benign vascular malformation
      whose growth causes cranial nerve compression. Although frequently missed on
      routine neuroimaging, characteristic radiologic findings distinguish it from
      lesions such as meningioma.

PMID- 24751813
TI  - Genome-wide association study supports the role of the immunological system and
      of the neurodevelopmental processes in response to haloperidol treatment.
AB  - AIM: The aim of the study was to detect the genetic predictors of reseponse to
      haloperidol. BACKGROUND: Haloperidol is a benchmark drug for the pharmacological
      treatment of schizophrenia, but the genetics of its efficacy is yet to be
      elucidated. METHODS: A genome-wide association analysis was carried out in a
      small sample of patients treated with haloperidol (n=96) and the results were
      replicated in a larger sample of patients treated with second-generation
      antipsychotics or perphenazine (final n=169, available from the Clinical
      Antipsychotic Trials for Intervention Effectiveness study). The Positive and
      Negative Symptom Scale % score decrease was the outcome in both samples. The
      period of observation was restricted to 1 month in the replication sample and the
      most severe cases were included to best balance the replication. The quality
      control (QC) for the investigation and replication sample included a minor allele
      frequency at least 0.01, call rate at least 0.95, and Hardy-Weinberg equilibrium
      P at least 0.0001. The source for imputation was the 1000 Genomes Pilot+HapMap 3
      dataset. In total 1 080 870 single nucleotide polymorphisms (SNPs) were available
      after imputation and QC in the investigation sample. After QC of real genotypes,
      locus-targeted imputations were restricted to windows of 10 kb on either side of
      the sentinel SNP in the replication sample. Sentinel SNPs were the most
      significant findings in the investigation sample. Analysis of variance was the
      test of choice, PLINK, SNPTEST, and GTOOL were used in the analysis. RESULTS: Two
      SNPs (rs7912580 and rs2412459) were associated with response in both samples,
      respectively, located in an intergenic region between the AT-rich interactive
      domain 5B (ARID5B, MRF1-like) gene and rhotekin 2 (RTKN2) gene, an intronic
      region located in the eukaryotic translation initiation factor 2alpha kinase 4
      (EIF2AK4) gene (P=1.358e-06 and 0.015 for the Positive and Negative Symptom Scale
      % total score decrease in the investigation and replication samples,
      respectively). The direction of association was opposite in the two samples, a
      finding that is sometimes reported as a flip-flop association. CONCLUSION:
      Heterozygosis for the ancestral allele was associated with the best improvement
      in the investigation sample and with poorer outcome in the replication sample.
      This discrepancy can be because of differences in the replication and
      investigation sample including the drugs used and the severity at baseline.
      Nevertheless, this finding is in line with two relevant hypothesis of
      schizophrenia, related to alterations in the immunological system (RTKN2) and in
      the neurodevelopment of the central nervous system (EIF2AK4). More studies are
      warranted to further investigate these associations.

PMID- 24751812
TI  - Genome-wide microRNA expression profiles in hippocampus of rats with chronic
      temporal lobe epilepsy.
AB  - The expression and functions of microRNAs (miRNAs) in chronic temporal lobe
      epilepsy (TLE), the most common type of refractory epilepsy in adults, are poorly
      understood currently. In this study, status epilepticus evoked by amygdala
      stimulation was used to establish rat chronic TLE model. Two months later, high
      throughput sequencing was employed to investigate miRNA expression profile in rat
      hippocampus, and six miRNAs were confirmed to be differentially expressed. Kyoto
      Encyclopedia of Genes and Genomes pathway analysis indicated that most of the
      target genes for these six miRNAs were associated with neuronal apoptosis.
      Meanwhile, the levels of miR-423-3p and miR-296-5p were correlated with the
      activity of caspase-3, an apoptosis indicator. Additionally, the loading of miR
      423-3p was increased in RNA-induced silencing complex whilst caspase-6, a target
      of miR-423-3p, was reduced in chronic TLE rats. Collectively, our findings
      suggest that miRNAs may exert anti-apoptotic effects in chronic TLE. 

PMID- 24751814
TI  - Hybrid perineurioma-neurofibroma in a patient with neurofibromatosis type 1,
      clinically mimicking malignant peripheral nerve sheath tumor.

PMID- 24751815
TI  - Proactively managing the risk of marketed drugs: experience with the EMA
      Pharmacovigilance Risk Assessment Committee.

PMID- 24751817
TI  - John P. A. Ioannidis.

PMID- 24751818
TI  - R&D productivity: on the comeback trail.

PMID- 24751816
TI  - Targeting bromodomains: epigenetic readers of lysine acetylation.
AB  - Lysine acetylation is a key mechanism that regulates chromatin structure;
      aberrant acetylation levels have been linked to the development of several
      diseases. Acetyl-lysine modifications create docking sites for bromodomains,
      which are small interaction modules found on diverse proteins, some of which have
      a key role in the acetylation-dependent assembly of transcriptional regulator
      complexes. These complexes can then initiate transcriptional programmes that
      result in phenotypic changes. The recent discovery of potent and highly specific
      inhibitors for the BET (bromodomain and extra-terminal) family of bromodomains
      has stimulated intensive research activity in diverse therapeutic areas,
      particularly in oncology, where BET proteins regulate the expression of key
      oncogenes and anti-apoptotic proteins. In addition, targeting BET bromodomains
      could hold potential for the treatment of inflammation and viral infection. Here,
      we highlight recent progress in the development of bromodomain inhibitors, and
      their potential applications in drug discovery. 

PMID- 24751820
TI  - Increased risk of Parkinson's disease in patients with end-stage renal disease: a
      retrospective cohort study.
AB  - BACKGROUND: Studies on dyskinesia and Parkinson's syndrome associated with
      chronic kidney disease or end-stage renal disease (ESRD) have been mainly limited
      to case reports or case series studies. This population-based study investigated
      the risk of Parkinson's disease in patients with ESRD. METHODS: From a universal
      insurance claims database of Taiwan, we established a cohort of 8,325 adults with
      newly diagnosed ESRD from 1997 to 2010 without a history of Parkinson's disease.
      A control cohort of 33,382 insured subjects without a history of kidney disease
      or Parkinson's disease was also selected, with frequency matched for age, sex and
      index date of the patients with ESRD. Both cohorts were followed up until the end
      of 2010. RESULTS: The Parkinson's disease incidence was 1.55-fold higher in the
      cohort with ESRD than in the comparison cohort (48.8 vs. 31.7 per 10,000 person
      years) with an adjusted hazard ratio of 1.73 (95% confidence interval, 1.39
      2.15). Sex-specific and age-specific analysis showed a higher relative risk for
      women and younger patients with ESRD compared to the control cohort. CONCLUSIONS:
      ESRD is significantly associated with an increased risk of Parkinson's disease.
      Close surveillance for Parkinson's disease should be considered for patients with
      ESRD.

PMID- 24751819
TI  - Interleukin-21: a double-edged sword with therapeutic potential.
AB  - Interleukin-21 is a cytokine with broad pleiotropic actions that affect the
      differentiation and function of lymphoid and myeloid cells. Since its discovery
      in 2000, a tremendous amount has been learned about its biological actions and
      the molecular mechanisms controlling IL-21-mediated cellular responses. IL-21
      regulates both innate and adaptive immune responses, and it not only has key
      roles in antitumour and antiviral responses but also exerts major effects on
      inflammatory responses that promote the development of autoimmune diseases and
      inflammatory disorders. Numerous studies have shown that enhancing or inhibiting
      the action of IL-21 has therapeutic effects in animal models of a wide range of
      diseases, and various clinical trials are underway. The current challenge is to
      understand how to specifically modulate the actions of IL-21 in the context of
      each specific immune response or pathological situation. In this Review, we
      provide an overview of the basic biology of IL-21 and discuss how this
      information has been - and can be - exploited therapeutically. 

PMID- 24751823
TI  - TALEN-mediated Drosophila genome editing: protocols and applications.
AB  - TALEs (transcription activator-like effectors) are a family of natural
      transcriptional activators originally isolated from the plant pathogen of
      Xanthomonas spp. The DNA binding motif of TALEs can be re-designed in such way
      that they bind specific DNA sequences other than their original targets. Fusion
      of customized TALEs with an endonuclease, Fok I, generates artificial enzymes
      that are targeted to specific DNA sites for cutting, allowing gene specific
      modification of both animal and plant genomes. Previously, we reported the use of
      TALEN (transcription activator-like effector nuclease) for the highly specific
      and efficient modification of the two Drosophila loci yellow and CG9797. Here, we
      describe a detailed protocol for TALEN-mediated genomic modification in
      Drosophila, with the aim of providing a practical bench guide for the Drosophila
      research community. 

PMID- 24751821
TI  - Effects of transgenic Cry1Ac + CpTI cotton on non-target mealybug pest Ferrisia
      virgata and its predator Cryptolaemus montrouzieri.
AB  - Recently, several invasive mealybugs (Hemiptera: Pseudococcidae) have rapidly
      spread to Asia and have become a serious threat to the production of cotton
      including transgenic cotton. Thus far, studies have mainly focused on the effects
      of mealybugs on non-transgenic cotton, without fully considering their effects on
      transgenic cotton and trophic interactions. Therefore, investigating the
      potential effects of mealybugs on transgenic cotton and their key natural enemies
      is vitally important. A first study on the effects of transgenic cotton on a non
      target mealybug, Ferrisia virgata (Cockerell) (Hemiptera: Pseudococcidae) was
      performed by comparing its development, survival and body weight on transgenic
      cotton leaves expressing Cry1Ac (Bt toxin) + CpTI (Cowpea Trypsin Inhibitor) with
      those on its near-isogenic non-transgenic line. Furthermore, the development,
      survival, body weight, fecundity, adult longevity and feeding preference of the
      mealybug predator Cryptolaemus montrouzieri Mulsant (Coleoptera: Coccinellidae)
      was assessed when fed F. virgata maintained on transgenic cotton. In order to
      investigate potential transfer of Cry1Ac and CpTI proteins via the food chain,
      protein levels in cotton leaves, mealybugs and ladybirds were quantified.
      Experimental results showed that F. virgata could infest this bivalent transgenic
      cotton. No significant differences were observed in the physiological parameters
      of the predator C. montrouzieri offered F. virgata reared on transgenic cotton or
      its near-isogenic line. Cry1Ac and CpTI proteins were detected in transgenic
      cotton leaves, but no detectable levels of both proteins were present in the
      mealybug or its predator when reared on transgenic cotton leaves. Our bioassays
      indicated that transgenic cotton poses a negligible risk to the predatory
      coccinellid C. montrouzieri via its prey, the mealybug F. virgata. 

PMID- 24751822
TI  - Evaluation of a single dose of ferric carboxymaltose in fatigued, iron-deficient
      women--PREFER a randomized, placebo-controlled study.
AB  - BACKGROUND: Unexplained fatigue is often left untreated or treated with
      antidepressants. This randomized, placebo-controlled, single-blinded study
      evaluated the efficacy and tolerability of single-dose intravenous ferric
      carboxymaltose (FCM) in iron-deficient, premenopausal women with symptomatic,
      unexplained fatigue. METHODS: Fatigued women (Piper Fatigue Scale [PFS] score
      >=5) with iron deficiency (ferritin <50 ug/L and transferrin saturation <20%, or
      ferritin <15 ug/L) and normal or borderline hemoglobin (>=115 g/L) were enrolled
      in 21 sites in Austria, Germany, Sweden and Switzerland, blinded to the study
      drug and randomized (computer-generated randomization sequence) to a single FCM
      (1000 mg iron) or saline (placebo) infusion. Primary endpoint was the proportion
      of patients with reduced fatigue (>=1 point decrease in PFS score from baseline
      to Day 56). RESULTS: The full analysis included 290 women (FCM 144, placebo 146).
      Fatigue was reduced in 65.3% (FCM) and 52.7% (placebo) of patients (OR 1.68,
      95%CI 1.05-2.70; p = 0.03). A 50% reduction of PFS score was achieved in 33.3%
      FCM- vs. 16.4% placebo-treated patients (p<0.001). At Day 56, all FCM-treated
      patients had hemoglobin levels >=120 g/L (vs. 87% at baseline); with placebo, the
      proportion decreased from 86% to 81%. Mental quality-of-life (SF-12) and the
      cognitive function scores improved better with FCM. 'Power of attention' improved
      better in FCM-treated patients with ferritin <15 ug/L. Treatment-emergent adverse
      events (placebo 114, FCM 209; most frequently headache, nasopharyngitis, pyrexia
      and nausea) were mainly mild or moderate. CONCLUSION: A single infusion of FCM
      improved fatigue, mental quality-of-life, cognitive function and erythropoiesis
      in iron-deficient women with normal or borderline hemoglobin. Although more side
      effects were reported compared to placebo, FCM can be an effective alternative in
      patients who cannot tolerate or use oral iron, the common treatment of iron
      deficiency. Overall, the results support the hypothesis that iron deficiency can
      affect women's health, and a normal iron status should be maintained independent
      of hemoglobin levels. TRIAL REGISTRATION: ClinicalTrials.gov NCT01110356.

PMID- 24751824
TI  - Studying aging in Drosophila.
AB  - Drosophila melanogaster represents one of the most important genetically
      accessible model organisms for aging research. Studies in flies have identified
      single gene mutations that influence lifespan and have characterized endocrine
      signaling interactions that control homeostasis systemically. Recent studies have
      focused on the effects of aging on specific tissues and physiological processes,
      providing a comprehensive picture of age-related tissue dysfunction and the loss
      of systemic homeostasis. Here we review methodological aspects of this work and
      highlight technical considerations when using Drosophila to study aging and age
      related diseases. 

PMID- 24751825
TI  - Hygromycin B and apramycin antibiotic resistance cassettes for use in
      Campylobacter jejuni.
AB  - Campylobacter jejuni genetic manipulation is restricted by the limited number of
      antibiotic resistance cassettes available for use in this diarrheal pathogen. In
      this study, two antibiotic resistance cassettes were developed, encoding for
      hygromycin B and apramycin resistance, for use in mutagenesis or for selection of
      gene expression and complementation constructs in C. jejuni. First, the marker
      genes were successfully modified to allow for insertional mutagenesis or deletion
      of a gene-of-interest, and were bracketed with restriction sites for the
      facilitation of site-specific cloning. These hygromycin B and apramycin markers
      are encoded by plasmids pAC1H and pAC1A, respectively. We also modified an
      insertional gene-delivery vector to create pRRH and pRRA, containing the
      hygromycin B and apramycin resistance genes, and 3 unique restriction sites for
      the directional introduction of genes into the conserved multi-copy rRNA gene
      clusters of the C. jejuni chromosome. We determined the effective antibiotic
      concentrations required for selection, and established that no harmful effects or
      fitness costs were associated with carrying hygromycin B or apramycin resistance
      under standard C. jejuni laboratory conditions. Using these markers, the
      arylsulfatase reporter gene astA was deleted, and the ability to genetically
      complement the astA deletion using pRRH and pRRA for astA gene insertion was
      demonstrated. Furthermore, the relative levels of expression from the endogenous
      astA promoter were compared to that of polycistronic mRNA expression from the
      constitutive promoter upstream of the resistance gene. The development of
      additional antibiotic resistance cassettes for use in Campylobacter will enable
      multiple gene deletion and expression combinations as well as more in-depth study
      of multi-gene systems important for the survival and pathogenesis of this
      important bacterium. 

PMID- 24751826
TI  - Taking stock: A multistakeholder perspective on improving the delivery of care
      and the development of treatments for Alzheimer's disease.
AB  - Health-care stakeholders increasingly recognize that the scientific and economic
      challenges associated with Alzheimer's disease (AD) are simply too great for
      individual stakeholder groups to address solely from within their own silos. In
      the necessary spirit of collaboration, we present in this perspective a set of
      multicountry multistakeholder recommendations to improve the organization of
      existing AD and dementia care and the development of new treatments. In brief,
      the five recommendations are (1) health-care systems must make choices regarding
      the patient populations to be diagnosed and treated, (2) health-care systems
      should use an evidence-based standard of care, (3) increased collaboration
      between public and private institutions is needed to enhance research, (4)
      reimbursement end points need to be agreed on and validated, and (5) innovative
      business models should be used to spur the introduction of new medicines.

PMID- 24751828
TI  - Proximal tubule toll-like receptor 4 expression linked to inflammation and
      apoptosis following hypoxia/reoxygenation injury.
AB  - BACKGROUND: Toll-like receptor 4 (TLR4) plays a key role in mediating kidney
      damage during ischemia/reperfusion (I/R) injury, and its expression is enhanced
      following renal I/R injury. Our study focused on TLR4 silencing-mediated
      downstream antiapoptotic pathways during hypoxia/reoxygenation (H/R) and
      investigated whether TLR4 overexpression exacerbates the renal damage induced by
      I/R injury. METHODS: Proximal tubule epithelial cells (PTECs) were isolated and
      H/R injury mediated by ATP depletion, and replenishment was performed to mimic in
      vivo I/R injury. PTECs were transfected with either TLR4 siRNA or TLR4
      overexpressing vectors to determine the contribution of TLR4 to H/R injury
      induced apoptosis and inflammatory response. RESULTS: H/R injury significantly
      enhanced PTEC apoptosis (p < 0.01) and the production of tumor necrosis factor
      (TNF)-alpha and interleukin (IL)-8; however, TLR4 silencing significantly
      reversed these effects (p < 0.05). Moreover, compared to PTECs or PTECs-siCon
      exposed to H/R injury, overexpression of TLR4 further upregulated TNF-alpha and
      IL-8 (p < 0.05), but did not enhance apoptosis. The expression of cytochrome C
      and caspases 3, 8, and 9 was decreased in the siTLR4 group compared to controls
      after H/R injury, whereas TLR4 silencing did not alter CHOP expression. TLR4
      overexpression failed to promote the expression of cytochrome C and caspases 3,
      8, and 9, and reduced the expression of CHOP and GPR78. CONCLUSIONS: Knockdown of
      TLR4 could protect PTECs from H/R injury via inhibiting mitochondrial and death
      receptor pathways. TLR4 overexpression did not increase PTEC apoptosis induced by
      H/R injury due in part to the downregulation of CHOP.

PMID- 24751827
TI  - An empirically derived composite cognitive test score with improved power to
      track and evaluate treatments for preclinical Alzheimer's disease.
AB  - BACKGROUND: There is growing interest in the evaluation of preclinical
      Alzheimer's disease (AD) treatments. As a result, there is a need to identify a
      cognitive composite that is sensitive to track preclinical AD decline to be used
      as a primary endpoint in treatment trials. METHODS: Longitudinal data from
      initially cognitively normal, 70- to 85-year-old participants in three cohort
      studies of aging and dementia from the Rush Alzheimer's Disease Center were
      examined to empirically define a composite cognitive endpoint that is sensitive
      to detect and track cognitive decline before the onset of cognitive impairment.
      The mean-to-standard deviation ratios (MSDRs) of change over time were calculated
      in a search for the optimal combination of cognitive tests/subtests drawn from
      the neuropsychological battery in cognitively normal participants who
      subsequently progressed to clinical stages of AD during 2- and 5-year periods,
      using data from those who remained unimpaired during the same period to correct
      for aging and practice effects. Combinations that performed well were then
      evaluated for representation of relevant cognitive domains, robustness across
      individual years before diagnosis, and occurrence of selected items within top
      performing combinations. RESULTS: The optimal composite cognitive test score
      comprised seven cognitive tests/subtests with an MSDR = 0.964. By comparison, the
      most sensitive individual test score was Logical Memory Delayed Recall with an
      MSDR = 0.64. CONCLUSIONS: We have identified a composite cognitive test score
      representing multiple cognitive domains that has improved power compared with the
      most sensitive single test item to track preclinical AD decline and evaluate
      preclinical AD treatments. We are confirming the power of the composite in
      independent cohorts and with other analytical approaches, which may result in
      refinements, have designated it as the primary endpoint in the Alzheimer's
      Prevention Initiative's preclinical treatment trials for individuals at high
      imminent risk for developing symptoms due to late-onset AD.

PMID- 24751829
TI  - Impact of cytokine gene variants on the prediction and prognosis of
      hepatocellular carcinoma in patients with cirrhosis.
AB  - BACKGROUND & AIMS: Genetic polymorphisms modulate the expression of
      proinflammatory cytokines. We prospectively assessed the influence of 6 single
      nucleotide polymorphisms (SNPs) in TNFalpha, IL6, and IL1beta genes on the risk
      of hepatocellular carcinoma (HCC) in patients with cirrhosis. METHODS: TNFalpha
      (G-238A, C-863A, G-308A), IL6 (C-174G), and IL1beta (C-31T, C-511T) SNPs were
      assessed in 232 alcoholics and 253 HCV-infected patients with biopsy-proven
      cirrhosis, prospectively followed-up and screened for HCC. Their influence on HCC
      development was assessed using the Kaplan-Meier method. RESULTS: These variants
      did not influence the risk of HCC in alcoholic patients. Conversely, two variants
      influenced the risk of HCC occurrence in patients with HCV-related cirrhosis,
      namely the TNFalpha-308 (A) allele (HR = 2.4 [1.6-3.7], Log-rank <0.0001) and the
      IL1beta-31 (T) allele (HR = 1.5 [1.1-2.1], Log-rank = 0.004). When stratifying
      HCV-infected patients into four genotypic associations expected to progressively
      increase TNFalpha and IL1beta production, we observed increasing risk of HCC
      occurrence (Log-rank <0.0001) from group 1 to 4. The TNFalpha-308 (A) allele was
      the only genetic trait independently associated with risk of HCC in these
      patients, along with older age, male gender, BMI, and platelet count. These
      variables led to construction of a predictive score able to separate patients
      with HCV-related cirrhosis into three subgroups with progressively increasing 5
      year cumulative incidences of 4.7%, 14.1%, and 36.3%, respectively (Log-rank
      <0.0001). CONCLUSIONS: Genetic heterogeneity in the TNFalpha and IL1beta gene
      promoters influences the risk of HCC in patients with HCV-induced cirrhosis.
      These genetic data, when incorporated into clinical scores, are able to refine
      selection of risk classes of HCC.

PMID- 24751830
TI  - Human serum albumin, systemic inflammation, and cirrhosis.
AB  - Human serum albumin (HSA) is one of the most frequent treatments in patients with
      decompensated cirrhosis. Prevention of paracentesis-induced circulatory
      dysfunction, prevention of type-1 HRS associated with bacterial infections, and
      treatment of type-1 hepatorenal syndrome are the main indications. In these
      indications treatment with HSA is associated with improvement in survival.
      Albumin is a stable and very flexible molecule with a heart shape, 585 residues,
      and three domains of similar size, each one containing two sub-domains. Many of
      the physiological functions of HSA rely on its ability to bind an extremely wide
      range of endogenous and exogenous ligands, to increase their solubility in
      plasma, to transport them to specific tissues and organs, or to dispose of them
      when they are toxic. The chemical structure of albumin can be altered by some
      specific processes (oxidation, glycation) leading to rapid clearance and
      catabolism. An outstanding feature of HSA is its capacity to bind
      lipopolysaccharide and other bacterial products (lipoteichoic acid and
      peptidoglycan), reactive oxygen species, nitric oxide and other nitrogen reactive
      species, and prostaglandins. Binding to NO and prostaglandins are reversible, so
      they can be transferred to other molecules at different sites from their
      synthesis. Through these functions, HSA modulates the inflammatory reaction.
      Decompensated cirrhosis is a disease associated systemic inflammation, which
      plays an important role in the pathogenesis of organ or system
      dysfunction/failure. Although, the beneficial effects of HAS have been
      traditionally attributed to plasma volume expansion, they could also relate to
      its effects modulating systemic and organ inflammation. 

PMID- 24751831
TI  - Fasting protects liver from ischemic injury through Sirt1-mediated downregulation
      of circulating HMGB1 in mice.
AB  - BACKGROUND & AIMS: Fasting and calorie restriction are associated with a
      prolonged life span and an increased resistance to stress. The protective effects
      of fasting have been exploited for the mitigation of ischemic organ injury, yet
      the underlying mechanisms remain incompletely understood. Here, we investigated
      whether fasting protects liver against ischemia reperfusion (IR) through energy
      preserving or anti-inflammatory mechanisms. METHODS: Fasted C57BL6 mice were
      subjected to partial hepatic IR. Injury was assessed by liver enzymes and
      histology. Raw264-7 macrophage-like cells were investigated in vitro. Sirt1 and
      HMGB1 were inhibited using Ex527 and neutralizing antibodies, respectively.
      RESULTS: Fasting for one, but not two or three days, protected from hepatic IR
      injury. None of the investigated energy parameters correlated with the protective
      effects. Instead, inflammatory responses were dampened in one-day-fasted mice and
      in starved macrophages. Fasting alone led to a reduction in circulating HMGB1
      associated with cytoplasmic HMGB1 translocation, aggregate formation, and
      autophagy. Inhibition of autophagy re-elevated circulating HMGB1 and abolished
      protection in fasted mice, as did supplementation with HMGB1. In vitro, Sirt1
      inhibition prevented HMGB1 translocation, leading to elevated HMGB1 in the
      supernatant. In vivo, Sirt1 inhibition abrogated the fasting-induced protection,
      but had no effect in the presence of neutralizing HMGB1 antibody. CONCLUSIONS:
      Fasting for one day protects from hepatic IR injury via Sirt1-dependent
      downregulation of circulating HMGB1. The reduction in serum HMGB1 appears to be
      mediated by its engagement in the autophagic response. These findings integrate
      Sirt1, HMGB1, and autophagy into a common framework that underlies the anti
      inflammatory properties of short-term fasting.

PMID- 24751832
TI  - Role of desmoplasia in cholangiocarcinoma and hepatocellular carcinoma.

PMID- 24751833
TI  - PPAR-alpha dependent regulation of vanin-1 mediates hepatic lipid metabolism.
AB  - BACKGROUND & AIMS: Peroxisome proliferator-activated receptor alpha (PPARalpha)
      is a key regulator of hepatic fat oxidation that serves as an energy source
      during starvation. Vanin-1 has been described as a putative PPARalpha target gene
      in liver, but its function in hepatic lipid metabolism is unknown. METHODS: We
      investigated the regulation of vanin-1, and total vanin activity, by PPARalpha in
      mice and humans. Furthermore, the function of vanin-1 in the development of
      hepatic steatosis in response to starvation was examined in Vnn1 deficient mice,
      and in rats treated with an inhibitor of vanin activity. RESULTS: Liver
      microarray analyses reveals that Vnn1 is the most prominently regulated gene
      after modulation of PPARalpha activity. In addition, activation of mouse
      PPARalpha regulates hepatic- and plasma vanin activity. In humans, consistent
      with regulation by PPARalpha, plasma vanin activity increases in all subjects
      after prolonged fasting, as well as after treatment with the PPARalpha agonist
      fenofibrate. In mice, absence of vanin-1 exacerbates the fasting-induced increase
      in hepatic triglyceride levels. Similarly, inhibition of vanin activity in rats
      induces accumulation of hepatic triglycerides upon fasting. Microarray analysis
      reveal that the absence of vanin-1 associates with gene sets involved in liver
      steatosis, and reduces pathways involved in oxidative stress and inflammation.
      CONCLUSIONS: We show that hepatic vanin-1 is under extremely sensitive regulation
      by PPARalpha and that plasma vanin activity could serve as a readout of changes
      in PPARalpha activity in human subjects. In addition, our data propose a role for
      vanin-1 in regulation of hepatic TG levels during fasting.

PMID- 24751834
TI  - Structural basis for recognition of the type VI spike protein VgrG3 by a cognate
      immunity protein.
AB  - The bacterial type VI secretion system (T6SS) is used by donor cells to inject
      toxic effectors into receptor cells. The donor cells produce the corresponding
      immunity proteins to protect themselves against the effector proteins, thereby
      preventing their self-intoxication. Recently, the C-terminal domain of VgrG3 was
      identified as a T6SS effector. Information on the molecular mechanism of VgrG3
      and its immunity protein TsaB has been lacking. Here, we determined the crystal
      structures of native TsaB and the VgrG3C-TsaB complex. VgrG3C adopts a canonical
      phage-T4-lysozyme-like fold. TsaB interacts with VgrG3C through molecular
      mimicry, and inserts into the VgrG3C pocket.

PMID- 24751835
TI  - Optimal method and timing of intrauterine intervention in twin reversed arterial
      perfusion sequence: case study and meta-analysis.
AB  - INTRODUCTION: The objective of this study was to define the optimal method and
      timing of intervention in twin reversed arterial perfusion (TRAP) sequence.
      MATERIAL AND METHODS: During a period of 20 years (1993-2013), we performed
      endoscopic laser coagulation of umbilical cord vessels or intrafetal laser in 67
      pregnancies with TRAP sequence. These data were combined with those reported in
      the literature to determine the survival rate of the pump twin for different
      methods and timing of interventions. RESULTS: A variety of techniques were used
      to interrupt the blood supply to the acardiac twin. Most procedures were
      performed at or after 16 weeks, and with most methods the survival rate of the
      pump twin was about 80%. Good results were also obtained for triplet pregnancies.
      In 18 of 30 cases (60%) diagnosed at 11-14 weeks, there was spontaneous cessation
      of flow in the acardiac twin before planned intervention at 16-18 weeks, and in
      11 of these (61.1%) the pump twin died or suffered brain damage. In 103
      pregnancies treated by intrafetal laser at 12-27 weeks, there was no correlation
      between gestational age at treatment and survival rate, but there was an inverse
      association between gestational age at treatment and gestational age at birth.
      DISCUSSION: In TRAP sequence, survival may be improved by elective intervention
      at 12-14 weeks.

PMID- 24751837
TI  - Unexpected epilepsy model found in sea lions.

PMID- 24751838
TI  - Fishing for insight into leukemia relapse.

PMID- 24751840
TI  - Small molecule, big advance against Marburg virus.

PMID- 24751841
TI  - Spying on the gut with a bacterial reporter.

PMID- 24751843
TI  - Barn owls: why give a hoot?

PMID- 24751844
TI  - Temporary housing for hamsters.

PMID- 24751845
TI  - Response to Protocol Review scenario: A new facility and a deviation.

PMID- 24751846
TI  - Response to Protocol Review scenario: A word from USDA and OLAW.

PMID- 24751847
TI  - Response to Protocol Review scenario: Need scientific justification.

PMID- 24751849
TI  - An international resource for lab animal science.

PMID- 24751848
TI  - Response to Protocol Review scenario: Inappropriate animal housing.

PMID- 24751850
TI  - Caring for Peromyscus spp. in research environments.
AB  - Peromyscus spp. are the most abundant native North American mammals. They have
      gained popularity as research animals in the last 20 years, and this trend is
      expected to continue as new research tools, such as whole genome sequences,
      baseline physiological data and others, become available. Concurrently, advances
      have been made in the recommendations for the care of laboratory animals. The
      authors provide insight into how the Peromyscus Genetic Stock Center successfully
      breeds and maintains several stocks of deer mice and related species. This
      information is beneficial to researchers that plan to include Peromyscus spp. in
      their research programs.

PMID- 24751851
TI  - Effects of using the analgesic tramadol in mice undergoing embryo transfer
      surgery.
AB  - Embryo transfer is a surgical technique that is widely used in reproductive
      biotechnology. Despite the ethical obligation to relieve animals' post-operative
      pain, analgesia is not routinely provided after embryo transfer surgery because
      it has been suggested that analgesics may be detrimental to embryo survival.
      Studies suggest, however, that the potential for adverse effects varies depending
      on the type of analgesic used and the timing of its administration. The authors
      carried out a study to determine whether pre-operatively administered tramadol, a
      synthetic analogue of codeine, influenced birth rate, litter survival or the post
      operative body weights of surrogate dams. Compared with controls that were not
      given any analgesic, surrogate dams given tramadol had similar birth rates and
      similar body weights at all time points. The tramadol-treated surrogate dams
      showed a statistically significant increase in the number of offspring that
      survived to weaning. The authors conclude that pre-operatively administered
      tramadol does not harm the success rate of embryo transfer surgery and even may
      improve litter survival.

PMID- 24751852
TI  - Lab Animal Management syllabus, part 2.

PMID- 24751853
TI  - Knock, knock...

PMID- 24751854
TI  - Bridging the gap between wild and laboratory animals.

PMID- 24751855
TI  - Structural characterization of an acetylated glucomannan with antiinflammatory
      activity and gastroprotective property from Cyrtopodium andersonii.
AB  - A polysaccharide with an estimated weight-average molar mass of 5.35*10(5) was
      obtained from an aqueous extract of pseudobulbs of Cyrtopodium andersonii R. Br.
      It was composed of d-glucose and d-mannose in 1:3 molar ratio. Chemical and
      spectroscopic analyses revealed a linear structure of the polymer with a backbone
      composed of (1->4)-linked beta-d-glucopyranosyl and mannopyranosyl units slightly
      branched at C-2, C-3, and C-6 by side chains, as terminal non reducing residues
      of d-mannopyranose and d-glucopyranose. It was found to contain 14.6% of acetyl
      groups substituted at C-2 of (1->4)-linked beta-d-mannopyranosyl units. The
      acetylated glucomannan demonstrated antiinflammatory and antiulcerogenic
      activities. 

PMID- 24751856
TI  - 6-Triazolyl-6-deoxy-beta-cyclodextrin derivatives: synthesis, cellular toxicity,
      and phase-solubility study.
AB  - Heptakis{6-(4-hydroxymethyl-1H-[1,2,3]triazol-1-yl)-6-deoxy}-beta-cyclodextrin
      (HTbetaCD) and heptakis{6-(4-sulfonylmethyl-1H-[1,2,3]triazol-1-yl)-6-deoxy}-beta
      cyclodextrin (STbetaCD) were prepared using copper(I)-catalyzed azide-alkyne
      cycloaddition between 6-azido-6-deoxy-beta-CD and one of two alkynes, propargyl
      alcohol, and sodium propargyl sulfonate, respectively. The structures of HTbetaCD
      and STbetaCD were characterized by NMR techniques. NMR interpretations and
      computer modeling suggested that the limited freedom of rotation of the triazole
      moieties keeps HTbetaCD and STbetaCD rigid and compact. Water solubility tests of
      HTbetaCD and STbetaCD showed that the minimum water solubility of HTbetaCD and
      STbetaCD is at least 20times higher than that of beta-CD. MTT assay showed that
      HTbetaCD and STbetaCD did not influence the cell viability under 1mM. A phase
      solubility study of prednisolone with the CD derivatives showed increased
      solubility of prednisolone in the presence of increasing concentrations of
      HTbetaCD and STbetaCD. 

PMID- 24751859
TI  - The new postgraduate course in heart failure.

PMID- 24751857
TI  - Trends in the use, sociodemographic correlates, and undertreatment of
      prescription medications for chronic obstructive pulmonary disease among adults
      with chronic obstructive pulmonary disease in the United States from 1999 to
      2010.
AB  - BACKGROUND: The extent to which patients with COPD are receiving indicated
      treatment with medications to improve lung function and recent trends in the use
      of these medications is not well documented in the United States. The objective
      of this study was to examine trends in prescription medications for COPD among
      adults in the United States from 1999 to 2010. METHODS: We performed a trend
      analysis using data from up to 1426 participants aged >=20 years with self
      reported COPD from six national surveys (National Health and Nutrition
      Examination Survey 1999-2010). RESULTS: During 2009-2010, the age-adjusted
      percentage of participants who used any kind of medication was 44.2%. Also during
      2009-2010, the most commonly used medications were short-acting agents (36.0%),
      inhaled corticosteroids (ICS) (18.3%), and LABAs (16.7%). The use of long-acting
      beta-2 agonists (LABAs) (p for trend <0.001), ICS (p for trend = 0.013) increased
      significantly over the 12-year period. Furthermore, the use of tiotropium
      increased rapidly during this period (p for trend <0.001). For the years 2005
      2010, the use of LABAs, ICS and tiotropium increased with age. Compared with
      whites, Mexican Americans were less likely to use short-acting agents, LABAs,
      ICS, tiotropium, and any kind of COPD medication. Among participants aged 20-79
      years with spirometry measurements during 2007-2010, the use of any medication
      was reported by 19.0% of those with a moderate/severe obstructive impairment and
      by 72.6% of those with self-reported COPD and any obstructive impairment.
      CONCLUSION: The percentages of adults with COPD who reported having various
      classes of prescription medications that improve airflow limitations changed
      markedly from 1999-2000 to 2009-2010. However, many adults with COPD did not
      report having recommended prescription medications.

PMID- 24751860
TI  - Revolutionizing the FRET-based light emission in core-shell nanostructures via
      comprehensive activity of surface plasmons.
AB  - We demonstrate the surface-plasmon-induced enhancement of Forster resonance
      energy transfer (FRET)using a model multilayer core-shell nanostructure
      consisting of an Au core and surrounding FRET pairs, i.e., CdSe quantum dot
      donors and S101 dye acceptors. The multilayer configuration was demonstrated to
      exhibit synergistic effects of surface plasmon energy transfer from the metal to
      the CdSe and plasmon-enhanced FRET from the quantum dots to the dye. With precise
      control over the distance between the components in the nanostructure,
      significant improvement in the emission of CdSe was achieved by combined
      resonance energy transfer and near-field enhancement by the metal, as well as
      subsequent improvement in the emission of dye induced by the enhanced emission of
      CdSe. Consequently, the Forster radius was increased to 7.92 nm and the FRET
      efficiency was improved to 86.57% in the tailored plasmonic FRET nanostructure
      compared to the conventional FRET system (22.46%) without plasmonic metals.

PMID- 24751861
TI  - Bronchiolitis and pneumonia requiring hospitalization in young first nations
      children in Northern Ontario, Canada.
AB  - BACKGROUND: High rates of lower respiratory tract infection (LRTI), including
      bronchiolitis and pneumonia, have been reported in Inuit infants living in arctic
      Canada. We examined rates of LRTI in First Nations Canadian infants living in the
      Sioux Lookout Zone, in Northern Ontario. METHODS: A retrospective review of
      hospital admissions for LRTI during a 5-year period, in patients <1 year of age
      was carried out at the Sioux Lookout Meno Ya Win Health Centre, an acute-care
      hospital that provides secondary care to 31 mainly isolated communities and the
      town of Sioux Lookout. Admission rates were compared with those in the province
      of Ontario, as a whole. RESULTS: One-hundred and seventeen subjects were
      identified. The annualized rate of admission for nonbacterial LRTI was 44 per
      1000 infants <1 year of age per year. This rate was significantly higher than for
      the whole province (P = 0.011). Admission rates also varied significantly between
      communities (P < 0.001).Thirteen percent of subjects required transfer to a
      tertiary care center. A virus was identified in 55% (36/65) of subjects tested
      for respiratory viruses, and respiratory syncytial virus and parainfluenza virus
      were identified most often. Of patients who had a blood culture performed,
      bacteria were found in 10% (6/59) of subjects. Many patients had radiographic
      evidence of consolidation, consistent with pneumonia. CONCLUSIONS: Rates of LRTI
      are significantly elevated in First Nations infants living in the Sioux Lookout
      Zone. Varying rates between communities suggest that environmental factors may be
      contributing to rates of LRTI in this population.

PMID- 24751862
TI  - Intussusception after monovalent human rotavirus vaccine in Australia: severity
      and comparison of using healthcare database records versus case confirmation to
      assess risk.
AB  - BACKGROUND: Surveillance for intussusception (IS) has been recommended in
      countries using rotavirus vaccine, but can be resource intensive. There is little
      data about the relative severity of rotavirus vaccine-associated IS compared with
      other IS cases. We collected detailed clinical data on all cases to evaluate the
      validity of ICD coding for IS in routinely collected data and case severity.
      METHODS: Hospitalizations and emergency department presentations coded as IS in
      infants aged <12 months from July 1, 2007, to June 30, 2010, were classified
      using Brighton criteria by case note review. We used self-controlled case series
      analysis to estimate IS risk after vaccination for all and only Brighton level 1
      cases. RESULTS: Of 179 unique episodes coded as IS, 110 (61%) met Brighton level
      1 criteria; self-controlled case series analysis found a relative incidence of IS
      in days 1-7 after the first dose of RV1 of 11.1 (95% confidence interval: 2.6
      48.0). When all coded episodes of IS were included, relative incidence was 4.0
      (95% confidence interval: 1.3-12.7). The proportion of Brighton 1 cases requiring
      surgery was 39% for those within 21 days of vaccine receipt and 34% for others (P
      = 0.67). CONCLUSIONS: Using ICD-coded cases without individual confirmation
      yielded a lower point estimate of risk for IS post rotavirus vaccination;
      however, the risk remained statistically compatible with that for chart confirmed
      cases only. Analysis using healthcare databases to evaluate risk of IS if
      conducted without case confirmation may be insufficient to confirm a low-level
      risk. IS episodes after vaccination were not more severe.

PMID- 24751863
TI  - Association between breast-feeding and severity of acute viral respiratory tract
      infection.
AB  - In a cross-sectional analysis of 629 mother-infants dyads, breast-feeding (ever
      vs. never) was associated with decreased relative odds of a lower versus upper
      respiratory tract infection (adjusted odds ratio: 0.64; 95% confidence interval:
      0.42-0.99). There was not a significant association between breast-feeding and
      bronchiolitis severity score or length of hospital stay. 

PMID- 24751864
TI  - Residents'corner April 2014. Editorial: what's new this month?

PMID- 24751865
TI  - Encoding range minima and range top-2 queries.
AB  - We consider the problem of encoding range minimum queries (RMQs): given an array
      A[1..n] of distinct totally ordered values, to pre-process A and create a data
      structure that can answer the query RMQ(i,j), which returns the index containing
      the smallest element in A[i..j], without access to the array A at query time. We
      give a data structure whose space usage is 2n+o(n) bits, which is asymptotically
      optimal for worst-case data, and answers RMQs in O(1) worst-case time. This
      matches the previous result of Fischer and Heun, but is obtained in a more
      natural way. Furthermore, our result can encode the RMQs of a random array A in
      1.919n+o(n) bits in expectation, which is not known to hold for Fischer and
      Heun's result. We then generalize our result to the encoding range top-2 query
      (RT2Q) problem, which is like the encoding RMQ problem except that the query
      RT2Q(i,j) returns the indices of both the smallest and second smallest elements
      of A[i..j]. We introduce a data structure using 3.272n+o(n) bits that answers
      RT2Qs in constant time, and also give lower bounds on the effective entropy of
      the RT2Q problem. 

PMID- 24751866
TI  - On the relationship between histogram indexing and block-mass indexing.
AB  - Histogram indexing, also known as jumbled pattern indexing and permutation
      indexing is one of the important current open problems in pattern matching. It
      was introduced about 6 years ago and has seen active research since. Yet, to date
      there is no algorithm that can preprocess a text T in time o(|T|(2)/polylog|T|)
      and achieve histogram indexing, even over a binary alphabet, in time independent
      of the text length. The pattern matching version of this problem has a simple
      linear-time solution. Block-mass pattern matching problem is a recently
      introduced problem, motivated by issues in mass-spectrometry. It is also an
      example of a pattern matching problem that has an efficient, almost linear-time
      solution but whose indexing version is daunting. However, for fixed finite
      alphabets, there has been progress made. In this paper, a strong connection
      between the histogram indexing problem and the block-mass pattern indexing
      problem is shown. The reduction we show between the two problems is amazingly
      simple. Its value lies in recognizing the connection between these two apparently
      disparate problems, rather than the complexity of the reduction. In addition, we
      show that for both these problems, even over unbounded alphabets, there are
      algorithms that preprocess a text T in time o(|T|(2)/polylog|T|) and enable
      answering indexing queries in time polynomial in the query length. The
      contributions of this paper are twofold: (i) we introduce the idea of allowing a
      trade-off between the preprocessing time and query time of various indexing
      problems that have been stumbling blocks in the literature. (ii) We take the
      first step in introducing a class of indexing problems that, we believe, cannot
      be pre-processed in time o(|T|(2)/polylog|T|) and enable linear-time query
      processing. 

PMID- 24751867
TI  - Fast computation of a string duplication history under no-breakpoint-reuse.
AB  - In this paper, we provide an O(n log(2) n log log n log* n) algorithm to compute
      a duplication history of a string under no-breakpoint-reuse condition. The
      motivation of this problem stems from computational biology, in particular, from
      analysis of complex gene clusters. The problem is also related to computing edit
      distance with block operations, but, in our scenario, the start of the history is
      not fixed, but chosen to minimize the distance measure. 

PMID- 24751868
TI  - A new graph model and algorithms for consistent superstring problems.
AB  - Problems related to string inclusion and non-inclusion have been vigorously
      studied in diverse fields such as data compression, molecular biology and
      computer security. Given a finite set of positive strings P and a finite set of
      negative strings N, a string alpha is a consistent superstring if every positive
      string is a substring of alpha and no negative string is a substring of alpha.
      The shortest (resp. longest) consistent superstring problem is to find a string
      alpha that is the shortest (resp. longest) among all the consistent superstrings
      for the given sets of strings. In this paper, we first propose a new graph model
      for consistent superstrings for given P and N. In our graph model, the set of
      strings represented by paths satisfying some conditions is the same as the set of
      consistent superstrings for P and N. We also present algorithms for the shortest
      and the longest consistent superstring problems. Our algorithms solve the
      consistent superstring problems for all cases, including cases that are not
      considered in previous work. Moreover, our algorithms solve in polynomial time
      the consistent superstring problems for more cases than the previous algorithms.
      For the polynomially solvable cases, our algorithms are more efficient than the
      previous ones.

PMID- 24751869
TI  - String search experimentation using massive data.
AB  - Descriptions of new string search or indexing algorithms are often accompanied by
      an experimental evaluation. In this article, we provide guidance as to how such
      investigations can be carried out, drawing on our experience of measurement in
      this field. In particular, we describe methodologies for stratifying patterns
      according to their length and frequency, so that precise response-time
      measurements can be made; and we describe a metric for categorizing the extent of
      'repetitiveness' in a text, so that dataset type can also be factored into
      evaluations. We show that separating these concepts allows a greater
      understanding of the behaviour of string search algorithms. 

PMID- 24751870
TI  - On integrating multi-experiment microarray data.
AB  - With the extensive use of microarray technology as a potential prognostic and
      diagnostic tool, the comparison and reproducibility of results obtained from the
      use of different platforms is of interest. The integration of those datasets can
      yield more informative results corresponding to numerous datasets and microarray
      platforms. We developed a novel integration technique for microarray gene
      expression data derived by different studies for the purpose of a two-way
      Bayesian partition modelling which estimates co-expression profiles under subsets
      of genes and between biological samples or experimental conditions. The suggested
      methodology transforms disparate gene-expression data on a common probability
      scale to obtain inter-study-validated gene signatures. We evaluated the
      performance of our model using artificial data. Finally, we applied our model to
      six publicly available cancer gene-expression datasets and compared our results
      with well-known integrative microarray data methods. Our study shows that the
      suggested framework can relieve the limited sample size problem while reporting
      high accuracies by integrating multi-experiment data. 

PMID- 24751871
TI  - Hybrid indexes for repetitive datasets.
AB  - Advances in DNA sequencing mean that databases of thousands of human genomes will
      soon be commonplace. In this paper, we introduce a simple technique for reducing
      the size of conventional indexes on such highly repetitive texts. Given upper
      bounds on pattern lengths and edit distances, we pre-process the text with the
      lossless data compression algorithm LZ77 to obtain a filtered text, for which we
      store a conventional index. Later, given a query, we find all matches in the
      filtered text, then use their positions and the structure of the LZ77 parse to
      find all matches in the original text. Our experiments show that this also
      significantly reduces query times. 

PMID- 24751872
TI  - Large-scale detection of repetitions.
AB  - Combinatorics on words began more than a century ago with a demonstration that an
      infinitely long string with no repetitions could be constructed on an alphabet of
      only three letters. Computing all the repetitions (such as ???TTT ??? or ???
      CGACGA ??? ) in a given string x of length n is one of the oldest and most
      important problems of computational stringology, requiring time in the worst
      case. About a dozen years ago, it was discovered that repetitions can be computed
      as a by-product of the Theta(n)-time computation of all the maximal periodicities
      or runs in x. However, even though the computation is linear, it is also brute
      force: global data structures, such as the suffix array, the longest common
      prefix array and the Lempel-Ziv factorization, need to be computed in a
      preprocessing phase. Furthermore, all of this effort is required despite the fact
      that the expected number of runs in a string is generally a small fraction of the
      string length. In this paper, I explore the possibility that repetitions (perhaps
      also other regularities in strings) can be computed in a manner commensurate with
      the size of the output.

PMID- 24751873
TI  - An optimal algorithm for computing all subtree repeats in trees.
AB  - Given a labelled tree T, our goal is to group repeating subtrees of T into
      equivalence classes with respect to their topologies and the node labels. We
      present an explicit, simple and time-optimal algorithm for solving this problem
      for unrooted unordered labelled trees and show that the running time of our
      method is linear with respect to the size of T. By unordered, we mean that the
      order of the adjacent nodes (children/neighbours) of any node of T is irrelevant.
      An unrooted tree T does not have a node that is designated as root and can also
      be referred to as an undirected tree. We show how the presented algorithm can
      easily be modified to operate on trees that do not satisfy some or any of the
      aforementioned assumptions on the tree structure; for instance, how it can be
      applied to rooted, ordered or unlabelled trees. 

PMID- 24751874
TI  - Indexing a sequence for mapping reads with a single mismatch.
AB  - Mapping reads against a genome sequence is an interesting and useful problem in
      computational molecular biology and bioinformatics. In this paper, we focus on
      the problem of indexing a sequence for mapping reads with a single mismatch. We
      first focus on a simpler problem where the length of the pattern is given
      beforehand during the data structure construction. This version of the problem is
      interesting in its own right in the context of the next generation sequencing. In
      the sequel, we show how to solve the more general problem. In both cases, our
      algorithm can construct an efficient data structure in O(n log(1+epsilon) n) time
      and space and can answer subsequent queries in O(m log log n + K) time. Here, n
      is the length of the sequence, m is the length of the read, 0<epsilon<1 and is
      the optimal output size.

PMID- 24751875
TI  - Storage and indexing of massive data.

PMID- 24751876
TI  - Preparation of uniformly (13)C,(15)N-labeled recombinant human amylin for solid
      state NMR investigation.
AB  - A number of diseases are caused by the formation of amyloid fibrils. Detailed
      understanding of structural features of amyloid fibers is of great importance for
      our understanding of disease progression and design of agents for diagnostics or
      potential prevention of protein aggregation. In lack of 3D crystal ordering,
      solid-state NMR forms the most suited method to determine the structures of the
      fibrils with atomic resolution. To exploit this potential, large amounts of
      isotopic-labeled protein need to be obtained through recombinant protein
      expression. However, expression and purification of amyloidogenic proteins in
      large amounts remains challenging due to their aggregation potential, toxicity
      for cells and difficult purification. In this work, we report a method for the
      production of large amounts of uniformly labeled (13)C,(15)N-human amylin, being
      one of the most amyloidogenic peptides known. This method utilizes inclusion
      bodies-directed expression and cheap chemical cleavage with cyanogen bromide in
      order to minimize the cost of the procedure compared to the use of less efficient
      proteolytic enzymes. We demonstrate the formation of amylin fibrils in vitro
      characterized using biophysical methods and electron microscopy, show toxicity
      towards human cells, and demonstrate that produced material may form the basis
      for structure determination using solid-state NMR. 

PMID- 24751877
TI  - A streamlined method for preparing split intein for NMR study.
AB  - A protein ligase, intein, mediates a protein-splicing reaction. It can be split
      into two complementary fragments and reconstituted as a whole intein scaffold to
      perform protein trans-splicing. To understand the association of intein fragments
      and the splicing mechanism, it is necessary to produce a large quantity of split
      intein for structural study. Conventionally, two fragments are prepared
      separately and assembled in solution, but severe aggregation of intein fragments
      occurs, and precise control of the relative concentration of each fragment is
      difficult. Here, we present a streamlined method to incorporate a circular
      permutation concept into the production of split intein. By circular permutation
      of the native split Nostoc punctiforme DnaE intein (NpuInt), a new backbone
      opening is relocated to the native split site at residue 102. As the protein
      splicing activity is preserved, the expressed NpuInt can immediately self-cleave
      into a two-piece split NpuInt. Because of a tight association between the two
      complementary fragments, split NpuInt can be purified in one step. The idea is
      simple and applicable to other split inteins. Employing the new preparation, we
      use NMR spectra to assign the backbone and side chain resonances for the native
      split NpuInt. 

PMID- 24751878
TI  - Anti-inflammatory activity of bone morphogenetic protein signaling pathways in
      stomachs of mice.
AB  - BACKGROUND & AIMS: Bone morphogenetic protein (BMP)4 is a mesenchymal peptide
      that regulates cells of the gastric epithelium. We investigated whether BMP
      signaling pathways affect gastric inflammation after bacterial infection of mice.
      METHODS: We studied transgenic mice that express either the BMP inhibitor noggin
      or the beta- galactosidase gene under the control of a BMP-responsive element and
      BMP4(betagal/+) mice. Gastric inflammation was induced by infection of mice with
      either Helicobacter pylori or Helicobacter felis. Eight to 12 weeks after
      inoculation, gastric tissue samples were collected and immunohistochemical,
      quantitative, reverse-transcription polymerase chain reaction and immunoblot
      analyses were performed. We used enzyme-linked immunosorbent assays to measure
      cytokine levels in supernatants from cultures of mouse splenocytes and dendritic
      cells, as well as from human gastric epithelial cells (AGS cell line). We also
      measured the effects of BMP-2, BMP-4, BMP-7, and the BMP inhibitor LDN-193189 on
      the expression of interleukin (IL)8 messenger RNA by AGS cells and primary
      cultures of canine parietal and mucus cells. The effect of BMP-4 on NFkB
      activation in parietal and AGS cells was examined by immunoblot and luciferase
      assays. RESULTS: Transgenic expression of noggin in mice increased H pylori- or H
      felis-induced inflammation and epithelial cell proliferation, accelerated the
      development of dysplasia, and increased expression of the signal transducer and
      activator of transcription 3 and activation-induced cytidine deaminase. BMP-4 was
      expressed in mesenchymal cells that expressed alpha-smooth muscle actin and
      activated BMP signaling pathways in the gastric epithelium. Neither BMP-4
      expression nor BMP signaling were detected in immune cells of C57BL/6, BRE-beta
      galactosidase, or BMP-4(betagal/+) mice. Incubation of dendritic cells or
      splenocytes with BMP-4 did not affect lipopolysaccharide-stimulated production of
      cytokines. BMP-4, BMP-2, and BMP-7 inhibited basal and tumor necrosis factor
      alpha-stimulated expression of IL8 in canine gastric epithelial cells. LDN-193189
      prevented BMP4-mediated inhibition of basal and tumor necrosis factor alpha
      stimulated expression of IL8 in AGS cells. BMP-4 had no effect on TNFalpha
      stimulated phosphorylation and degradation of IkappaBalpha, or on TNFalpha
      induction of a NFkappabeta reporter gene. CONCLUSIONS: BMP signaling reduces
      inflammation and inhibits dysplastic changes in the gastric mucosa after
      infection of mice with H pylori or H felis.

PMID- 24751879
TI  - Differential angiogenic properties of lithium chloride in vitro and in vivo.
AB  - Wnt/beta-catenin signaling induced by the Norrin/Frizzled-4 pathway has been
      shown to improve capillary repair following oxygen induced retinopathy (OIR) in
      the mouse, a model for retinopathy of prematurity. Here we investigated if
      treatment with the monovalent cation lithium that has been shown to augment
      Wnt/beta-catenin signaling in vitro and in vivo has similar effects. In cultured
      human microvascular endothelial cells, LiCl as well as SB 216763, another small
      molecule that activates Wnt/beta-catenin signaling, induced proliferation,
      survival and migration, which are all common parameters for angiogenic properties
      in vitro. Moreover, treatment with both agents caused an increase in the levels
      of beta-catenin and their translocation to nuclei while quercetin, an inhibitor
      of Wnt/beta-catenin signaling, completely blocked the effects of LiCl on
      proliferation. In mice with OIR, intraperitonal or intravitreal treatment with
      LiCl markedly increased the retinal levels of beta-catenin, but did not improve
      capillary repair. In contrast, repair was significantly improved following
      intravitreal treatment with Norrin. The effects of LiCl on HDMEC in vitro have
      minor relevance for OIR in vivo, and the influence of the Norrin/Frizzled-4
      pathway on capillary repair in OIR is not reproducible upon enhancing Wnt/beta
      catenin signaling by LiCl treatment strongly indicating the presence of
      additional and essential mechanisms. 

PMID- 24751881
TI  - Neuroendocrine cancer. An activating hotspot mutation in PRKACA provides clues
      for adrenal Cushing syndrome therapeutics.

PMID- 24751880
TI  - Insights from the Global Longitudinal Study of Osteoporosis in Women (GLOW).
AB  - GLOW is an observational, longitudinal, practice-based cohort study of
      osteoporosis in 60,393 women aged >=55 years in 10 countries on three continents.
      In this Review, we present insights from the first 3 years of the study. Despite
      cost analyses being frequently based on spine and hip fractures, we found that
      nonvertebral, nonhip fractures were around five times more common and doubled the
      use of health-care resources compared with hip and spine fractures combined.
      Fractures not at the four so-called major sites in FRAX((r)) (upper arm, forearm,
      hip and clinical vertebral fractures) account for >40% of all fractures. The risk
      of fracture is increased by various comorbidities, such as Parkinson disease,
      multiple sclerosis and lung and heart disease. Obesity, although thought to be
      protective against all fractures, substantially increased the risk of fractures
      in the ankle or lower leg. Simple assessment by age plus fracture history has
      good predictive value for all fractures, but risk profiles differ for first and
      subsequent fractures. Fractures diminish quality of life as much or more than
      diabetes mellitus, arthritis and lung disease, yet women substantially
      underestimate their own fracture risk. Treatment rates in patients at high risk
      of fracture are below those recommended but might be too frequent in women at low
      risk. Comorbidities and the limits of current therapeutic regimens jeopardize the
      efficacy of drugs; new regimens should be explored for severe cases. 

PMID- 24751882
TI  - Diabetes. Excess risk of stroke in women--the role of diabetes mellitus.
AB  - A growing body of literature examines the burden of sex-specific risk factors for
      cardiovascular disease. Women with diabetes mellitus have a higher risk of
      coronary heart disease than men with diabetes mellitus. A recent study provides
      strong evidence that women with diabetes mellitus also have an increased risk of
      stroke.

PMID- 24751883
TI  - Geographic and ethnic disparities in osteoporotic fractures.
AB  - Osteoporotic fractures are a major worldwide epidemic. Here, we review global
      variability, ethnic differences and secular changes in osteoporotic fractures.
      Worldwide, age-standardized incidence rates of hip fracture vary >200-fold in
      women and >140-fold in men when comparing the country in which incidence rates
      are the highest with that in which they are the lowest. Median age-standardized
      rates are highest in North America and Europe, followed by Asia, Middle East,
      Oceania, Latin America and Africa. Globally, rates of hip fracture are greater in
      women than in men, with an average ratio of ~2:1. The incidence of radiographic
      vertebral fractures is much higher than that of hip fractures, whereas the
      incidence rates of clinical vertebral fractures mirror hip fracture rates in most
      countries. Methodological challenges of defining and ascertaining vertebral
      fractures limit the interpretation of these data. Secular declines in hip
      fracture rates have been reported in populations from North America, Europe and
      Oceania. These declines are especially notable in women, suggesting that
      reproductive factors might contribute to this reduction. By contrast, hip
      fracture rates are increasing in parts of Asia and Latin America. Global
      indicators of health, education and socioeconomic status are positively
      correlated with fracture rates suggesting that lifestyles in developed countries
      might contribute to hip fracture. Improvements in fracture assessment, in
      particular for nonhip fractures, and identification of factors that contribute to
      this variability might substantially influence our understanding of osteoporotic
      fracture aetiology and provide new avenues for prevention. 

PMID- 24751884
TI  - Macrophages are the dominant effector cells responsible for IgG-mediated passive
      systemic anaphylaxis challenged by natural protein antigen in BALB/c and C57BL/6
      mice.
AB  - IgG-induced passive systemic anaphylaxis (PSA), a serious adverse effect of
      passive immune therapy using therapeutic monoclonal antibodies, has been greatly
      emphasized. However, controversy exists regarding the type of effector cells
      involved in IgG-induced anaphylaxis as a result of the induction of PSA by
      different IgG subtypes or the use of mice with varying genetic backgrounds. To
      clarify the effector cells for PSA, the PSA model with serious hypothermia was
      established by IgG monoclonal antibody (mAb) against natural protein or complete
      antigen, not hapten conjugate, in BALB/c and C57BL/6 mice. The results indicated
      that PSA could be remarkably inhibited by the depletion of macrophages but not by
      the depletion of whole leukocytes, basophils, neutrophils or monocytes. We
      further confirmed that macrophages are indispensable for the PSA induced by all
      six IgG-natural antigen complexes in both strains of mice. Additionally, platelet
      activating factor (PAF) was found to be the major effector mediator for IgG
      induced anaphylaxis. Moreover, gene knock-out of the third component of
      complement (C3) did not affect PSA-related hypothermia in C57BL/6 mice. These
      results indicate that macrophages and PAF act as dominant effector cells and
      mediator molecules, respectively, and are indispensable components in the
      induction of IgG-mediated PSA induced by IgG mAb and natural protein antigen.
      Based on the above results, we hypothesize that inconsistencies in effector cells
      for PSA may be associated with different features of the mAb-antigen system that
      might affect the magnitude of FcgammaRs cross-linking on effector cells. 

PMID- 24751886
TI  - Effects of allopurinol on endothelial dysfunction: a meta-analysis.
AB  - OBJECTIVE: Several studies have assessed the effect of allopurinol on endothelial
      function, but these studies were relatively small in size and used different
      methods of evaluating endothelial function. We conducted a meta-analysis to
      investigate the effect of allopurinol on both endothelial-dependent and 
      independent vasodilatation. METHODS: Electronic databases, Medline, PubMed,
      EMBASE, SCOPUS, EBSCO and the Cochrane Library Central Register of Clinical
      Trials were searched from January 1985 to July 2013 on clinical trials
      (randomized and non-randomized) which assessed the effect of allopurinol on
      endothelial function. We conducted a sensitivity analysis to assess the
      contribution of each study to the pooled treatment effect by excluding each study
      one at a time and recalculating the pooled treatment effect for the remaining
      studies. Treatment effect was significant if p < 0.05. We assessed for
      heterogeneity in treatment estimates using the Cochran Q test and the chi(2)
      statistic (with substantial heterogeneity defined as values >50%). RESULTS: The
      final analysis consisted of 11 studies (2 observational and 9 randomized). For
      the endothelial-dependent vasodilatation there were 6 studies, including 257
      patients, that evaluated flow-mediated dilatation and 5 studies with 87 patients
      that reported data on forearm blood flow response to acetylcholine or flow
      dependent vasodilatation. Overall, there was a significant increase in the
      endothelium-dependent vasodilatation with allopurinol treatment (MD 2.69%, 95% CI
      2.49, 2.89%, p < 0.001; heterogeneity chi(2) = 319.1, I(2) = 96%, p < 0.001).
      There was only 1 study (100 patients) assessing nitrate-mediated dilatation and 4
      studies (73 patients) evaluating forearm blood flow response to sodium
      nitroprusside as measures of endothelial-independent vasodilatation. The overall
      analysis (MD -0.08, 95% CI -0.50, 0.34, p = 0.70; heterogeneity chi(2) = 9.0,
      I(2) = 44%, p = 0.11) showed no effect of allopurinol treatment on endothelium
      independent vasodilatation. CONCLUSIONS: We found that treatment of hyperuricemia
      with allopurinol is associated with an improvement in the endothelial-dependent,
      but not with the endothelial-independent vasodilatation.

PMID- 24751885
TI  - Gene expression signatures affected by alcohol-induced DNA methylomic
      deregulation in human embryonic stem cells.
AB  - Stem cells, especially human embryonic stem cells (hESCs), are useful models to
      study molecular mechanisms of human disorders that originate during gestation.
      Alcohol (ethanol, EtOH) consumption during pregnancy causes a variety of prenatal
      and postnatal disorders collectively referred to as fetal alcohol spectrum
      disorders (FASDs). To better understand the molecular events leading to FASDs, we
      performed a genome-wide analysis of EtOH's effects on the maintenance and
      differentiation of hESCs in culture. Gene Co-expression Network Analysis showed
      significant alterations in gene profiles of EtOH-treated differentiated or
      undifferentiated hESCs, particularly those associated with molecular pathways for
      metabolic processes, oxidative stress, and neuronal properties of stem cells. A
      genome-wide DNA methylome analysis revealed widespread EtOH-induced alterations
      with significant hypermethylation of many regions of chromosomes.
      Undifferentiated hESCs were more vulnerable to EtOH's effect than their
      differentiated counterparts, with methylation on the promoter regions of
      chromosomes 2, 16 and 18 in undifferentiated hESCs most affected by EtOH
      exposure. Combined transcriptomic and DNA methylomic analysis produced a list of
      differentiation-related genes dysregulated by EtOH-induced DNA methylation
      changes, which likely play a role in EtOH-induced decreases in hESC pluripotency.
      DNA sequence motif analysis of genes epigenetically altered by EtOH identified
      major motifs representing potential binding sites for transcription factors.
      These findings should help in deciphering the precise mechanisms of alcohol
      induced teratogenesis. 

PMID- 24751887
TI  - N-terminal pro-brain natriuretic peptide is a useful prognostic marker in
      patients with pre-capillary pulmonary hypertension and renal insufficiency.
AB  - N-terminal pro-brain natriuretic peptide (NT-proBNP) is a routinely used
      prognostic parameter in patients with pre-capillary pulmonary hypertension (PH).
      As it accumulates in the presence of impaired renal function, the clinical
      utility of NT-proBNP in PH patients with concomitant renal insufficiency remains
      unclear. In a retrospective approach, patients with pre-capillary PH (group I or
      IV) and concomitant renal insufficiency at time of right heart catheterization
      (glomerular filtration rate (GFR) <=60 ml/min/1.73 m2) were identified out of all
      prevalent pre-capillary PH patients treated at a single center. Forty patients
      with renal insufficiency (25.8%) were identified and matched regarding
      hemodynamic parameters with a control group of 56 PH patients with normal renal
      function (GFR >60 ml/min/1.73 m2). Correlations of NT-proBNP levels with
      hemodynamic and prognostic parameters (time to clinical worsening and overall
      survival) were assessed. Overall, GFR correlated inversely with NT-proBNP and had
      the strongest influence on NT-proBNP levels in a stepwise multiple linear
      regression model including hemodynamic parameters and age (r2 = 0.167). PH
      patients with renal insufficiency had significant higher levels of NT-proBNP
      (median: 1935 ng/l vs. 573 ng/l, p = 0.001). Nevertheless, NT-proBNP correlated
      with invasive hemodynamic parameters in these patients. Using higher cut-off
      values than in patients with preserved renal function, NT-proBNP levels were
      significantly associated with time to clinical worsening (>1660 ng/l, p = 0.001)
      and survival (>2212 ng/l, p = 0.047) in patients with renal insufficiency.
      Multivariate Cox's proportional hazards analysis including established prognostic
      parameters, age and GFR confirmed NT-proBNP as an independent risk factor for
      clinical worsening in PH patients with renal insufficiency (hazard ratio 4.8, p =
      0.007). Thus, in a retrospective analysis we showed that NT-proBNP levels
      correlated with hemodynamic parameters and outcome regardless of renal function.
      By using higher cut-off values, NT-proBNP seems to represent a valid clinical
      marker even in PH patients with renal insufficiency. 

PMID- 24751888
TI  - Antibiotic-containing polymers for localized, sustained drug delivery.
AB  - Many currently used antibiotics suffer from issues such as systemic toxicity,
      short half-life, and increased susceptibility to bacterial resistance. Although
      most antibiotic classes are administered systemically through oral or intravenous
      routes, a more efficient delivery system is needed. This review discusses the
      chemical conjugation of antibiotics to polymers, achieved by forming covalent
      bonds between antibiotics and a pre-existing polymer or by developing novel
      antibiotic-containing polymers. Through conjugating antibiotics to polymers,
      unique polymer properties can be taken advantage of. These polymeric antibiotics
      display controlled, sustained drug release and vary in antibiotic class type,
      synthetic method, polymer composition, bond lability, and antibacterial activity.
      The polymer synthesis, characterization, drug release, and antibacterial
      activities, if applicable, will be presented to offer a detailed overview of each
      system. 

PMID- 24751890
TI  - Incidence of primary central nervous system germ cell tumors in childhood: a
      regional survey in Kumamoto prefecture in southern Japan.
AB  - BACKGROUND/AIMS: Central nervous system germ cell tumors (CNS-GCTs) are
      relatively rare. While their incidence was thought to be higher in East Asia than
      the USA, recent evidence suggests the difference between Japan and the USA is not
      statistically significant. The aim of this study was to determine the rate of
      pediatric primary CNS-GCTs in Kumamoto prefecture, Japan. METHODS: We surveyed
      6,615 new cases of primary intracranial tumors diagnosed in Kumamoto prefecture
      between 1989 and 2011. Among these, 251 (3.8%) occurred in patients younger than
      15 years. The age-adjusted incidence rates were calculated by the direct method
      using 5-year age groupings; the incidence in the total Japanese population in the
      year 2000 was the standard. RESULTS: During the 23-year period, 70 cases of
      primary GCT were diagnosed. Of these tumors, 31 (44.3%) arose in patients aged
      between 0 and 14 years (22 boys, 9 girls). Their tumor location was pineal in
      45.2%; the other sites were nonpineal. There were more germinomas (64.5%) than
      nongerminomas (35.5%) in this group. The age-adjusted annual incidence rate was
      0.45 cases (boys: 0.64, girls: 0.28) per 10(5) children. At 2.29, the ratio of
      CNS-GCTs was higher in these boys than girls. Our data showed higher rates than
      data from CBTRUS 2012 (0.18/10(5)), SEER 2008 (0.15/10(5)) and Germany
      (0.10/10(5)). CONCLUSIONS: Our survey showed that the incidence of primary CNS
      GCTs in children was higher in Kumamoto prefecture than in the USA and other
      Western countries, suggesting that racial backgrounds play a role.

PMID- 24751889
TI  - gamma-Secretase inhibitor DAPT attenuates intimal hyperplasia of vein grafts by
      inhibition of Notch1 signaling.
AB  - The proliferation and high plasticity of vascular smooth muscle cells (vSMCs) are
      the major reasons for restenosis of vein grafts. N-[N-(3, 5-difluorophenacetyl)-l
      alanyl]-S-phenylglycine t-butyl ester (DAPT), specific inhibitor of gamma
      secretase, has been shown to regulate vSMC proliferation and differentiation
      through the Notch signaling pathway, but the pathophysiological importance of
      these findings in venous grafts has not yet been determined. A rat vein graft
      model was employed wherein the left jugular vein was surgically interposed into
      the left common carotid artery. Daily subcutaneous injections of DAPT or placebo
      (DMSO) were administered postoperatively (control animals received no treatment).
      We showed that DAPT can inhibit restenosis of vein grafts by inhibiting vSMC
      proliferation and increasing apoptosis in vivo. Notch1 signaling was highly
      active during the development of intima thickening. By blocking the Notch
      signaling pathway, the gamma-secretase inhibitor DAPT can significantly
      attenuated intima thickening. These changes in vein grafts coincided with
      enhanced binding of myocardin to the smooth muscle-specific protein SM22 and
      smooth muscle myosin heavy chain at the promoters of vSMC differentiation
      specific genes. These studies showed that DAPT can restore the vSMC phenotype and
      inhibit vSMC proliferation through suppression of the Notch1 signaling pathway,
      and thus opens a new avenue for the treatment of restenosis in vein grafts. 

PMID- 24751892
TI  - The neonatal bowel microbiome in health and infection.
AB  - PURPOSE OF REVIEW: In newborns, interactions between the host and the microbiome
      operate synergistically, modulating host immune function and shaping the
      microbiome. Next generation molecular sequencing methodologies in tandem with
      modeling complex communities allow insights into the role of the microbiome in
      health and disease states. Infection-related disease states in which dysbiosis is
      integral include late-onset sepsis (LOS) and necrotizing enterocolitis (NEC),
      which still cause deaths and morbidity. Understanding microbiomic interactions
      may lead to alternative prevention, monitoring or treatment strategies, and
      modulation of long-term health outcomes especially in the preterm population.
      Recent studies have advanced understanding of the microbiome in NEC and LOS.
      RECENT FINDINGS: Mechanisms of host-microbiome interaction have been
      demonstrated. Patterns of microbiomic change in association with NEC and LOS have
      been observed, with community changes dominated by Proteobacteria and Firmicutes
      appearing to precede NEC, and very early microbiomic signatures influencing LOS.
      Data on viral and fungal elements are emerging. SUMMARY: Greater understanding of
      the neonatal bowel microbiome may allow tailored clinical practice and
      therapeutic intervention. Data handling and interpretation is challenging.
      Mechanistic studies of clinical interventions that affect the gut microbiome are
      important next steps.

PMID- 24751893
TI  - Managing multidrug-resistant tuberculosis in children: review of recent
      developments.
AB  - PURPOSE OF REVIEW: Childhood multidrug-resistant (MDR) tuberculosis is an
      emerging disease with increasing numbers being recognized. This review presents
      recent developments in childhood MDR tuberculosis. RECENT FINDINGS: New molecular
      based diagnostic tests, although not optimal, have reduced the difficulty in
      confirming the diagnosis of MDR tuberculosis in children. However, the importance
      of making a diagnosis of probable MDR tuberculosis has been reaffirmed by contact
      tracing studies showing 80-90% of child contacts of MDR tuberculosis cases who
      develop disease have MDR tuberculosis themselves. Prevention of MDR tuberculosis
      in child contacts with appropriate preventive treatment regimens is supported by
      new observational data and deserves further study. When diagnosed and treated
      appropriately, outcomes for MDR tuberculosis and even extensively drug-resistant
      tuberculosis in children are good, despite limited pharmacokinetic data on second
      line drugs. Novel anti-tuberculosis drugs and regimens are becoming available and
      should be studied in children for dose-finding and safety. Recording and
      reporting of MDR tuberculosis in children are frequently poor, leading to
      inaccurate estimates of disease burden and suboptimal resource planning. SUMMARY:
      Rapid diagnosis and appropriate treatment results in good outcomes in the
      majority of children with MDR tuberculosis. Additional research on optimal
      diagnosis, prevention and treatment of MDR tuberculosis in children remains a
      high priority.

PMID- 24751894
TI  - Mycoplasma pneumoniae in children: carriage, pathogenesis, and antibiotic
      resistance.
AB  - PURPOSE OF REVIEW: Both the diagnosis and treatment of Mycoplasma pneumoniae
      infections in children are currently facing two main challenges: a relatively
      high carriage in asymptomatic children, and a worldwide increase in macrolide
      resistant M. pneumoniae (MRMP). This review focuses on the scientific and
      clinical implications of these crucial issues. RECENT FINDINGS: Recent studies
      have indicated that the prevalence of M. pneumoniae in the upper respiratory
      tract is similar among asymptomatic, healthy children and children with a
      symptomatic respiratory tract infection, and that current diagnostic procedures
      for M. pneumoniae are unable to differentiate between bacterial carriage and
      infection. It is therefore possible that the burden of M. pneumoniae-associated
      disease is overestimated. Another phenomenon that has an important impact on the
      treatment of M. pneumoniae infections is the rapid worldwide emergence of MRMP
      isolates. SUMMARY: The current diagnostic procedures for M. pneumoniae cannot
      discern between bacterial carriage and infection in a clinically relevant time
      frame. It is therefore imperative that these procedures be modified such as to
      unambiguously detect symptomatic M. pneumoniae infections. Moreover, the
      emergence of MRMP necessitates the application of methods to detect macrolide
      resistance as well as the implementation of restrictive policies regarding the
      use of macrolides.

PMID- 24751891
TI  - Molecular characterization and expression analysis of chloroplast protein import
      components in tomato (Solanum lycopersicum).
AB  - The translocon at the outer envelope membrane of chloroplasts (Toc) mediates the
      recognition and initial import into the organelle of thousands of nucleus-encoded
      proteins. These proteins are translated in the cytosol as precursor proteins with
      cleavable amino-terminal targeting sequences called transit peptides. The
      majority of the known Toc components that mediate chloroplast protein import were
      originally identified in pea, and more recently have been studied most
      extensively in Arabidopsis. With the completion of the tomato genome sequencing
      project, it is now possible to identify putative homologues of the chloroplast
      import components in tomato. In the work reported here, the Toc GTPase cDNAs from
      tomato were identified, cloned and analyzed. The analysis revealed that there are
      four Toc159 homologues (slToc159-1, -2, -3 and -4) and two Toc34 homologues
      (slToc34-1 and -2) in tomato, and it was shown that tomato Toc159 and Toc34
      homologues share high sequence similarity with the comparable import apparatus
      components from Arabidopsis and pea. Thus, tomato is a valid model for further
      study of this system. The expression level of Toc complex components was also
      investigated in different tissues during tomato development. The two tomato Toc34
      homologues are expressed at higher levels in non-photosynthetic tissues, whereas,
      the expression of two tomato Toc159 homologues, slToc159-1 and slToc159-4, were
      higher in photosynthetic tissues, and the expression patterns of slToc159-2 was
      not significantly different in photosynthetic and non-photosynthetic tissues, and
      slToc159-3 expression was limited to a few select tissues. 

PMID- 24751895
TI  - Skin antisepsis in the neonate: what should we use?
AB  - PURPOSE OF REVIEW: Neonates in intensive care are more susceptible to sepsis.
      Infection is commonly acquired via the transcutaneous portal. It is necessary to
      identify the most effective yet safest topical antiseptics for use in neonates to
      reduce nosocomial sepsis. RECENT FINDINGS: Recent national surveys indicate that
      a wide range of topical antiseptic preparations are used in the neonatal nursery.
      There are very few comparative studies in neonates and no robust evidence in
      favour of any particular antiseptic. There are significant safety and potential
      toxicity issues for neonates with all the commonly used antiseptics, particularly
      in very small immature babies. There are no convincing roles for routine
      application of emollient creams on the skin, topical antiseptics on the umbilical
      stump, or maternal vaginal washes with chlorhexidine for the prevention of
      neonatal infection. SUMMARY: Large multicentre trials are needed to determine the
      optimal antiseptic to use for neonates undergoing intensive care, especially for
      extremely preterm infants.

PMID- 24751896
TI  - Clinical laboratory studies in Barth Syndrome.
AB  - Barth Syndrome is a rare X-linked disorder characterized principally by dilated
      cardiomyopathy, skeletal myopathy and neutropenia and caused by defects in
      tafazzin, an enzyme responsible for modifying the acyl chain moieties of
      cardiolipin. While several comprehensive clinical studies of Barth Syndrome have
      been published detailing cardiac and hematologic features, descriptions of its
      biochemical characteristics are limited. To gain a better understanding of the
      clinical biochemistry of this rare disease, we measured hematologic and
      biochemical values in a cohort of Barth Syndrome patients. We characterized
      multiple biochemical parameters, including plasma amino acids, plasma 3
      methylglutaconic acid, cholesterol, cholesterol synthetic intermediates, and red
      blood cell membrane fatty acid profiles in 28 individuals with Barth Syndrome
      from ages 10 months to 30 years. We describe a unique biochemical profile for
      these patients, including decreased plasma arginine levels. We further studied
      the plasma amino acid profiles, cholesterol, cholesterol synthetic intermediates,
      and plasma 3-methylglutaconic acid levels in 8 female carriers and showed that
      they do not share any of the distinct, Barth Syndrome-specific biochemical
      laboratory abnormalities. Our studies augment and expand the biochemical profiles
      of individuals with Barth Syndrome, describe a unique biochemical profile for
      these patients, and provide insight into the possible underlying biochemical
      pathology in this disorder.

PMID- 24751898
TI  - Real-time single-cell imaging of protein secretion.
AB  - Protein secretion, a key intercellular event for transducing cellular signals, is
      thought to be strictly regulated. However, secretion dynamics at the single-cell
      level have not yet been clarified because intercellular heterogeneity results in
      an averaging response from the bulk cell population. To address this issue, we
      developed a novel assay platform for real-time imaging of protein secretion at
      single-cell resolution by a sandwich immunoassay monitored by total internal
      reflection microscopy in sub-nanolitre-sized microwell arrays. Real-time
      secretion imaging on the platform at 1-min time intervals allowed successful
      detection of the heterogeneous onset time of nonclassical IL-1beta secretion from
      monocytes after external stimulation. The platform also helped in elucidating the
      chronological relationship between loss of membrane integrity and IL-1beta
      secretion. The study results indicate that this unique monitoring platform will
      serve as a new and powerful tool for analysing protein secretion dynamics with
      simultaneous monitoring of intracellular events by live-cell imaging. 

PMID- 24751899
TI  - Preoperative scoring and limits of prognostication: functional outcome after
      surgical decompression in metastatic spinal cord compression.
AB  - OBJECTIVE: To determine whether preoperative parameters correlate with the
      postoperative functional outcome in para- and tetraplegic patients with lung,
      kidney, breast and prostate cancer and metastatic spinal cord compression (MSCC).
      METHODS: Information on 43 patients undergoing decompressive surgery and
      rehabilitation for MSCC was reviewed, including primary tumor, age, pre- and
      postoperative ambulation status, mobility subcategory of the Spinal Cord Injury
      Measure (mSCIM) and the Tokuhashi score. Differences between groups were analyzed
      by the nonparametric chi(2) test, and correlation coefficients (Spearman's rho)
      were computed. RESULTS: Preoperative ambulation (p < 0.001), the American Spinal
      Injury Association Impairment Scale (p < 0.001) and the type of operation (p =
      0.02) influenced the postoperative functional outcome. Any positive change in the
      mSCIM was influenced by preoperative ambulation (p < 0.001). Patients with breast
      carcinoma showed significantly more positive changes in the mSCIM compared with
      other tumors (p = 0.002). No correlation was found between the treatment
      categories of the Tokuhashi score and the preoperative ambulatory status (p =
      0.13) or the change in ambulation status (p = 0.29). CONCLUSION: The
      postoperative functional outcome of MSCC patients shows a linear association
      between the categories of the Tokuhashi score and the change in ambulation
      status. We recommend surgical decompression even in a palliative situation
      (Tokuhashi score 0-8) with the aim of optimizing the short-term rehabilitation
      outcome.

PMID- 24751901
TI  - Expression of the LIM homeobox domain transcription factor ISL1 (Islet-1) is
      frequent in rhabdomyosarcoma but very limited in other soft tissue sarcoma types.
AB  - The transcription factor ISL1 (islet-1) has emerged as a useful marker for
      metastatic pancreatic well differentiated neuroendocrine neoplasms, but recent
      studies showed wider expression in poorly differentiated neuroendocrine
      carcinomas from different sites as well as poorly differentiated neuroblastoma.
      Expression of ISL1 in soft tissue sarcomas has not been studied before.We
      evaluated ISL1 expression in 249 soft tissue tumour specimens from 249 patients
      and 17 precursor cell lymphoblastic lymphomas (ALL). ISL1 was not detected in any
      of 63 liposarcomas of different subtypes, 55 leiomyosarcomas, 22 solitary fibrous
      tumours, 20 undifferentiated pleomorphic/spindle cell sarcomas, 13 small cell
      synovial sarcomas and 17 ALL cases. Variable nuclear expression was detected in
      rhabdomyosarcoma (15/25, 60%), rhabdomyoblastic areas of malignant mullerian
      mixed tumours (5/5), Ewing sarcoma (2/12, very weak) and monophasic fibrous
      synovial sarcoma (2/29). More extensive staining (moderate to strong) was
      restricted to rhabdomyosarcoma. Taken by histological subtype, ISL1 was expressed
      more frequently in alveolar (9/11, 82%) versus non-alveolar (6/14, 43%)
      rhabdomyosarcoma. ISL1 is commonly expressed in rhabdomyosarcoma, particularly
      the alveolar subtype and should be distinguished from poorly differentiated
      neuroendocrine and neuroblastic neoplasms. Awareness of this finding helps to
      avoid misinterpretation as neuroendocrine neoplasms that would result in
      inappropriate therapeutic and prognostic consequences.

PMID- 24751900
TI  - Abacavir induced T cell reactivity from drug naive individuals shares features of
      allo-immune responses.
AB  - Abacavir hypersensitivity is a severe hypersensitivity reaction which occurs
      exclusively in carriers of the HLA-B*57?01 allele. In vitro culture of PBMC with
      abacavir results in the outgrowth of abacavir-reacting CD8+ T cells, which
      release IFNgamma and are cytotoxic. How this immune response is induced and what
      is recognized by these T cells is still a matter of debate. We analyzed the
      conditions required to develop an abacavir-dependent T cell response in vitro.
      The abacavir reactivity was independent of co-stimulatory signals, as neither DC
      maturation nor release of inflammatory cytokines were observed upon abacavir
      exposure. Abacavir induced T cells arose in the absence of professional APC and
      stemmed from naive and memory compartments. These features are reminiscent of
      allo-reactivity. Screening for allo-reactivity revealed that about 5% of
      generated T cell clones (n = 136) from three donors were allo-reactive
      exclusively to the related HLA-B*58?01. The addition of peptides which can bind
      to the HLA-B*57?01-abacavir complex and to HLA-B*58?01 during the induction phase
      increased the proportion of HLA-B*58?01 allo-reactive T cell clones from 5% to
      42%. In conclusion, abacavir can alter the HLA-B*57?01-peptide complex in a way
      that mimics an allo-allele ('altered self-allele') and create the potential for
      robust T cell responses. 

PMID- 24751902
TI  - Syndecan 4 is involved in mediating HCV entry through interaction with lipoviral
      particle-associated apolipoprotein E.
AB  - Hepatitis C virus (HCV) is a major cause of liver disease worldwide and HCV
      infection represents a major health problem. HCV associates with host
      lipoproteins forming host/viral hybrid complexes termed lipoviral particles.
      Apolipoprotein E (apoE) is a lipoprotein component that interacts with heparan
      sulfate proteoglycans (HSPG) to mediate hepatic lipoprotein uptake, and may
      likewise mediate HCV entry. We sought to define the functional regions of apoE
      with an aim to identify critical apoE binding partners involved in HCV infection.
      Using adenoviral vectors and siRNA to modulate apoE expression we show a direct
      correlation of apoE expression and HCV infectivity, whereas no correlation exists
      with viral protein expression. Mutating the HSPG binding domain (HSPG-BD) of apoE
      revealed key residues that are critical for mediating HCV infection. Furthermore,
      a novel synthetic peptide that mimics apoE's HSPG-BD directly and competitively
      inhibits HCV infection. Genetic knockdown of the HSPG proteins syndecan (SDC) 1
      and 4 revealed that SDC4 principally mediates HCV entry. Our data demonstrate
      that HCV uses apoE-SDC4 interactions to enter hepatoma cells and establish
      infection. Targeting apoE-SDC interactions could be an alternative strategy for
      blocking HCV entry, a critical step in maintaining chronic HCV infection. 

PMID- 24751904
TI  - Residents'corner April 2014. sQUIZ your knowledge!: multiple nodular lesions on
      the leg.

PMID- 24751905
TI  - Motor and language abilities from early to late toddlerhood: using formalized
      assessments to capture continuity and discontinuity in development.
AB  - Developmental tests reflect the premise that decreases in skills over time should
      be a sign of atypical development. In contrast, from a psychological perspective,
      discontinuity may be viewed as a normal part of typical development. This study
      sought to describe the variability in patterns of continuity and discontinuity in
      developmental scores over time. Seventy-six toddlers (55% boys) from a larger
      screening study were evaluated at 13 and 30 months using the Mullen Scales of
      Early Development (MSEL) in five areas: gross motor, fine motor, visual
      perception, receptive language, and expressive language. Parents completed the
      First Year Inventory (FYI) at 12 months as well. At 30 months, 23.68% of the
      sample received a clinical diagnosis (e.g., developmental delay, autism spectrum
      disorder [ASD]). Toddlers were classified as stable, increasing, or decreasing by
      at least 1.5 standard deviations (SD) on their scores in each of the five MSEL
      areas from 13 to 30 months. Between 3.9% and 51.3% of the sample was classified
      as increasing and 0-23.7% as decreasing across areas. Decreases in motor areas
      were associated with increases in language areas. None of the toddlers showed
      decreases greater than 1.5 SD on their MSEL composite scores. There was no single
      pattern that characterized a certain diagnosis. Higher FYI sensory-regulatory
      risk was associated with decreases in gross motor. Lower FYI risk was linked with
      increases in receptive language. Developmental discontinuity in specific
      developmental areas was the rule rather than the exception. Interpretations of
      decreases in developmental levels must consider concurrent increases in skill
      during this emerging period.

PMID- 24751903
TI  - PEG-IFN alpha but not ribavirin alters NK cell phenotype and function in patients
      with chronic hepatitis C.
AB  - BACKGROUND: Ribavirin (RBV) remains part of several interferon-free treatment
      strategies even though its mechanisms of action are still not fully understood.
      One hypothesis is that RBV increases responsiveness to type I interferons.
      Pegylated Interferon alpha (PEG-IFNa) has recently been shown to alter natural
      killer (NK) cell function possibly contributing to control of hepatitis C virus
      (HCV) infection. However, the effects of ribavirin alone or in combination with
      IFNa on NK cells are unknown. METHODS: Extensive ex vivo phenotyping and
      functional analysis of NK cells from hepatitis C patients was performed during
      antiviral therapy. Patients were treated for 6 weeks with RBV monotherapy (n =
      11), placebo (n = 13) or PEG-IFNa-2a alone (n = 6) followed by PEG-IFNa/RBV
      combination therapy. The effects of RBV and PEG-IFNa-2a on NK cells were also
      studied in vitro after co-culture with K562 or Huh7.5 cells. RESULTS: Ribavirin
      monotherapy had no obvious effects on NK cell phenotype or function, neither ex
      vivo in patients nor in vitro. In contrast, PEG-IFNa-2a therapy was associated
      with an increase of CD56bright cells and distinct changes in expression profiles
      leading to an activated NK cell phenotype, increased functionality and decline of
      terminally differentiated NK cells. Ribavirin combination therapy reduced some of
      the IFN effects. An activated NK cell phenotype during therapy was inversely
      correlated with HCV viral load. CONCLUSIONS: PEG-IFNa activates NK cells possibly
      contributing to virological responses independently of RBV. The role of NK cells
      during future IFN-free combination therapies including RBV remains to be
      determined.

PMID- 24751906
TI  - Analysis of reading strategies in deaf adults as a function of their language and
      meta-phonological skills.
AB  - The first aim of this study was to examine the mechanisms used in reading
      sentences by deaf adults who had completed secondary or higher education.
      Previous data allowed us to hypothesize that they used the key word strategy,
      consisting of identifying (some of) the frequent content words, and deriving an
      overall representation of the sentence's meaning ignoring the function words. The
      results supported the hypothesis. The second aim was to establish the
      relationships between this strategy and the linguistic and phonological abilities
      of deaf participants. The results show that vocabulary increased with reading
      level, but syntax, evaluated with the use of function words, did not. This
      suggests that using the key word strategy during long periods of time increases
      knowledge of content words but not syntax, probably because function words are
      neglected by this strategy. The results also showed that the deaf participants
      had a fairly large orthographical lexicon. This implies that the extensive use of
      the key word strategy allows them to store lexical information. The next question
      was whether the written word representations of the deaf participants were
      memorized as mere logograms, or if they had been stored in connection with the
      phonological representations of the corresponding words. The metaphonological
      tasks conducted produced evidence indicating that deaf participants used both
      orthographic and phonological representations. A factor analysis of the
      metaphonological tasks together with reading and spelling confirmed that both
      factors were necessary to explain the whole variance in the deaf group.

PMID- 24751907
TI  - Implicit learning and reading: insights from typical children and children with
      developmental dyslexia using the artificial grammar learning (AGL) paradigm.
AB  - We examined implicit learning in school-aged children with and without
      developmental dyslexia based on the proposal that implicit learning plays a
      significant role in mastering fluent reading. We ran two experiments with 16
      typically developing children (9 to 11-years-old) and 16 age-matched children
      with developmental dyslexia using the artificial grammar learning (AGL) paradigm.
      In Experiment 1 (non-transfer task), children were trained on stimuli that
      followed patterns (rules) unknown to them. Subsequently, they were asked to
      decide from a novel set which stimuli follow the same rules (grammaticality
      judgments). In Experiment 2 (transfer task), training and testing stimuli
      differed in their superficial characteristics but followed the same rules. Again,
      children were asked to make grammaticality judgments. Our findings expand upon
      previous research by showing that children with developmental dyslexia show
      difficulties in implicit learning that are most likely specific to higher-order
      rule-like learning. These findings are discussed in relation to current theories
      of developmental dyslexia and of implicit learning.

PMID- 24751908
TI  - Expression of Caveolin 1 is enhanced by DNA demethylation during adipocyte
      differentiation. status of insulin signaling.
AB  - Caveolin 1 (Cav-1) is an essential constituent of adipocyte caveolae which binds
      the beta subunit of the insulin receptor (IR) and is implicated in the regulation
      of insulin signaling. We have found that, during adipocyte differentiation of 3T3
      L1 cells the promoter, exon 1 and first intron of the Cav-1 gene undergo a
      demethylation process that is accompanied by a strong induction of Cav-1
      expression, indicating that epigenetic mechanisms must have a pivotal role in
      this differentiation process. Furthermore, IR, PKB-Akt and Glut-4 expression are
      also increased during the differentiation process suggesting a coordinated
      regulation with Cav-1. Activation of Cav-1 protein by phosphorylation arises
      during the differentiation process, yet in fully mature adipocytes insulin is no
      longer able to significantly increase Cav-1 phosphorylation. However, these long
      term differentiated cells are still able to respond adequately to insulin,
      increasing IR and PKB-Akt phosphorylation and glucose uptake. The activation of
      Cav-1 during the adipocyte differentiation process could facilitate the
      maintenance of insulin sensitivity by these fully mature adipocytes isolated from
      additional external stimuli. However, under the influence of physiological
      conditions associated to obesity, such as chronic inflammation and hypoxia,
      insulin sensitivity would finally be compromised. 

PMID- 24751909
TI  - Collective choice in ants: the role of protein and carbohydrates ratios.
AB  - In a foraging context, social insects make collective decisions from individuals
      responding to local information. When faced with foods varying in quality, ants
      are known to be able to select the best food source using pheromone trails. Until
      now, studies investigating collective decisions have focused on single nutrients,
      mostly carbohydrates. In the environment, the foods available are a complex
      mixture and are composed of various nutrients, available in different forms. In
      this paper, we explore the effect of protein to carbohydrate ratio on ants'
      ability to detect and choose between foods with different protein characteristics
      (free amino acids or whole proteins). In a two-choice set up, Argentine ants
      Linepithema humile were presented with two artificial foods containing either
      whole protein or amino acids in two different dietary conditions: high protein
      food or high carbohydrate food. At the collective level, when ants were faced
      with high carbohydrate foods, they did not show a preference between free amino
      acids or whole proteins, while a preference for free amino acids emerged when
      choosing between high protein foods. At the individual level, the probability of
      feeding was higher for high carbohydrates food and for foods containing free
      amino acids. Two mathematical models were developed to evaluate the importance of
      feeding probability in collective food selection. A first model in which a
      forager deposits pheromone only after feeding, and a second model in which a
      forager always deposits pheromone, but with greater intensity after feeding. Both
      models were able to predict free amino acid selection, however the second one was
      better able to reproduce the experimental results suggesting that modulating
      trail strength according to feeding probability is likely the mechanism
      explaining amino acid preference at a collective level in Argentine ants. 

PMID- 24751910
TI  - A role for the gut microbiota in IBS.
AB  - The past decade has witnessed an explosion of knowledge regarding the vast
      microbial community that resides within our intestine-the gut microbiota. The
      topic has generated great expectations in terms of gaining a better understanding
      of disorders ranging from IBD to metabolic disorders and obesity. IBS is a
      condition for which investigators have long been in search of plausible
      underlying pathogeneses and it is inevitable that altered composition or function
      of the gut microbiota will be considered as a potential aetiological factor in at
      least a subset of patients with IBS. This Review describes the evidence
      implicating the gut microbiota in not only the expression of the intestinal
      manifestations of IBS, but also the psychiatric morbidity that coexists in up to
      80% of patients with IBS. The evidence described herein ranges from proof-of
      concept studies in animals to observational studies and clinical trials in
      humans. The gut microbiota is subject to influences from a diverse range of
      factors including diet, antibiotic usage, infection and stress. These factors
      have previously been implicated in the pathophysiology of IBS and further prompt
      consideration of a role for the gut microbiota in IBS. 

PMID- 24751911
TI  - Ulcerative colitis: mouse model reveals how appendicitis protects against
      ulcerative colitis.

PMID- 24751912
TI  - Advances in the management of the explanted donor liver.
AB  - Liver transplantation is the best therapy in end-stage liver disease. Donor organ
      shortage and efforts to expand the donor organ pool are permanent issues given
      that advances in perioperative management and immunosuppressive therapy have
      brought the procedure into widespread clinical use. The management of organ
      procurement, including donor preconditioning and adequate organ storage, has a
      key role in transplantation. However, the organ procurement process can differ
      substantially between transplant centres, depending on local and national
      preferences. Advances in the field have come from experimental and clinical
      research on dynamic storage systems, such as machine perfusion devices, as an
      alternative to static cold storage. Determination of the clinical significance of
      these new systems is a topic worthy of future investigations. 

PMID- 24751913
TI  - Colorectal cancer: serrated polyposis--should we screen first-degree relatives?
AB  - Serrated polyposis syndrome (SPS) is a condition characterized by multiple and/or
      proximal serrated polyps in the colorectum. Several features of SPS suggest there
      is an underlying genetic disorder that is yet to be identified. A new study
      provides insights on the diagnostic yield of screening colonoscopy in first
      degree relatives of patients with SPS.

PMID- 24751914
TI  - Diagnosis and treatment of narcotic bowel syndrome.
AB  - With increased prescription of opioids has come increased recognition of adverse
      consequences, including narcotic bowel syndrome (NBS). Characterized by
      incompletely controlled abdominal pain despite continued or increasing doses of
      opioids, NBS is estimated to occur in 4.2-6.4% of patients chronically taking
      opioids. Patients with NBS have a high degree of comorbid psychiatric illness,
      catastrophizing and disability; comorbid substance abuse must also be considered
      among this population. NBS should be distinguished from opioid-induced bowel
      disorder, which results from the effects of opioids on gastrointestinal motility
      and secretion. By contrast, the mechanisms of NBS are probably centrally mediated
      and include glial cell activation, bimodal opioid modulation in the dorsal horn,
      descending facilitation of pain and the glutaminergic system. Few treatments have
      been rigorously studied. A trial of opioid detoxification resulted in complete
      detoxification for the vast majority of patients with reduction in pain symptoms;
      however, despite improvement in pain, approximately half of patients returned to
      opioid use within 3 months. Improved strategies are needed to identify patients
      who will respond to detoxification and remain off opioids. Comorbid psychiatric
      and substance abuse disorders are barriers to durable response after
      detoxification and should be actively sought out and treated accordingly. An
      effective patient-physician relationship is essential. 

PMID- 24751915
TI  - Maternal and paternal parenting practices and their influence on children's
      adiposity, screen-time, diet and physical activity.
AB  - The primary aim of this study was to examine a range of potential behavioral and
      maternal/paternal correlates of adiposity in children. Secondary aims were to
      examine (a) correlates of screen-time, diet and physical activity and (b) if
      there were differences in maternal and paternal physical activity- and dietary
      related parenting practices. Cross-sectional analysis was conducted using 70
      families with children (59% boys (41/70), mean age 8.4 (+/-2.4) years). Parenting
      practices were measured using the Parenting Strategies for Eating and Activity
      Scale. Children's outcomes included: 7-day pedometry (physical activity), screen
      time, percent energy from core foods (Food frequency questionnaire) and BMI z
      score. Multiple regression models were generated to examine the associations
      between maternal and paternal parenting practices and children's variables. In
      the regression analyses, fathers' BMI (p < .01) and mothers' control (p < .001)
      were significantly associated with child weight status. Fathers' reinforcement (p
      < .01) was significantly associated with child physical activity. For screen
      time, mothers' monitoring (p < .001) and child characteristics [age (p = .01),
      sex (p = .01), BMI z-score (p = .03)] were significant predictors. Mothers'
      parenting practices [limit setting (p = .01), reinforcement (p = .02)] and child
      screen-time (p = .02) were significantly associated with intake of core foods.
      Despite some similarities within families, three out of five parenting constructs
      were significantly different between mothers and fathers. Mothers and fathers
      have different parental influences on their children's weight status and
      lifestyle behaviors and both should be included in lifestyle interventions
      targeting children. A focus on maternal parenting specifically relating to screen
      time and diet, and father's physical activity parenting and weight status may
      support their children in developing more healthy behaviors. 

PMID- 24751916
TI  - Night eating in patients with type 2 diabetes. Associations with glycemic
      control, eating patterns, sleep, and mood.
AB  - Night eating is a complex behavior associated with disruptions in eating, sleep,
      and mood regulation. While night eating has been associated with alterations in
      neuroendocrine functioning, night eating and Night Eating Syndrome (NES) are not
      well understood in patients with prevalent metabolic conditions, such as
      diabetes. In this study, 194 adults with Type 2 diabetes completed questionnaires
      assessing night eating symptoms as well as eating, sleep, and depressive
      symptoms. Glycemic control data, as measured by hemoglobin A1c (HbA1c), were
      gathered from patient medical charts. Results indicated that 7% of participants
      met criteria for NES. Increased symptoms of night eating were associated with
      poorer glycemic control and disruptions in eating, sleep, and mood, including
      significantly increased likelihood of having HbA1c levels >7% and endorsing
      clinical levels of depressive symptoms. Increasing understanding of the
      relationship between night eating and metabolic and psychosocial functioning in
      patients with diabetes may provide new avenues for treatment of these patients. 

PMID- 24751917
TI  - Promoting consumption of fruit and vegetables for better health. Have campaigns
      delivered on the goals?
AB  - Daily intake of fruits and vegetables worldwide remains well below the
      recommended WHO levels, despite the established health benefits associated with
      fruit and vegetable consumption. A diversity of policy interventions designed to
      increase consumption have been conducted in the developed economies around the
      globe for over a decade, involving significant monetary outlays. The impact of
      these initiatives remains at best, modest to low, in effecting a significant
      increase in daily consumption on a sustained basis. Several factors have been
      identified in both promoting and impeding the increase in fruit and vegetable
      consumption, including the effects of consumer behaviour. This paper reviews
      several of the major promotional campaigns from around the world and provides
      analysis of their level of success, with a view to developing novel approaches
      for formulating more effective marketing and promotional interventions that will
      prompt significant change. 

PMID- 24751918
TI  - On the role of the gap junction protein Cx43 (GJA1) in human cardiac
      malformations with Fallot-pathology. a study on paediatric cardiac specimen.
AB  - INTRODUCTION: Gap junction channels are involved in growth and differentiation.
      Therefore, we wanted to elucidate if the main cardiac gap junction protein
      connexin43 (GJA1) is altered in patients with Tetralogy of Fallot or double
      outlet right ventricle of Fallot-type (62 patients referred to as Fallot)
      compared to other cardiac anomalies (21 patients referred to as non-Fallot).
      Patients were divided into three age groups: 0-2years, 2-12years and >12years.
      Myocardial tissue samples were collected during corrective surgery and analysis
      of cell morphology, GJA1- and N-cadherin (CDH2)-distribution, as well as GJA1
      protein- and mRNA-expression was carried out. Moreover, GJA1-gene analysis of 16
      patients and 20 healthy subjects was performed. RESULTS: Myocardial cell length
      and width were significantly increased in the oldest age group compared to the
      younger ones. GJA1 distribution changed significantly during maturation with the
      ratio of polar/lateral GJA1 increasing from 2.93+/-0.68 to 8.52+/-1.41. While in
      0-2years old patients ~6% of the lateral GJA1 was co-localised with CDH2 this
      decreased with age. Furthermore, the changes in cell morphology and GJA1
      distribution were not due to the heart defect itself but were significantly
      dependent on age. Total GJA1 protein expression decreased during growing-up,
      whereas GJA1-mRNA remained unchanged. Sequencing of the GJA1-gene revealed only
      few heterozygous single nucleotide polymorphisms within the Fallot and the
      healthy control group. CONCLUSION: During maturation significant changes in gap
      junction remodelling occur which might be necessary for the growing and
      developing heart. In our study point mutations within the Cx43-gene could not be
      identified as a cause of the development of TOF.

PMID- 24751919
TI  - HD CAGnome: a search tool for huntingtin CAG repeat length-correlated genes.
AB  - BACKGROUND: The length of the huntingtin (HTT) CAG repeat is strongly correlated
      with both age at onset of Huntington's disease (HD) symptoms and age at death of
      HD patients. Dichotomous analysis comparing HD to controls is widely used to
      study the effects of HTT CAG repeat expansion. However, a potentially more
      powerful approach is a continuous analysis strategy that takes advantage of all
      of the different CAG lengths, to capture effects that are expected to be critical
      to HD pathogenesis. METHODOLOGY/PRINCIPAL FINDINGS: We used continuous and
      dichotomous approaches to analyze microarray gene expression data from 107 human
      control and HD lymphoblastoid cell lines. Of all probes found to be significant
      in a continuous analysis by CAG length, only 21.4% were so identified by a
      dichotomous comparison of HD versus controls. Moreover, of probes significant by
      dichotomous analysis, only 33.2% were also significant in the continuous
      analysis. Simulations revealed that the dichotomous approach would require
      substantially more than 107 samples to either detect 80% of the CAG-length
      correlated changes revealed by continuous analysis or to reduce the rate of
      significant differences that are not CAG length-correlated to 20% (n = 133 or n =
      206, respectively). Given the superior power of the continuous approach, we
      calculated the correlation structure between HTT CAG repeat lengths and gene
      expression levels and created a freely available searchable website, "HD
      CAGnome," that allows users to examine continuous relationships between HTT CAG
      and expression levels of ~20,000 human genes. CONCLUSIONS/SIGNIFICANCE: Our
      results reveal limitations of dichotomous approaches compared to the power of
      continuous analysis to study a disease where human genotype-phenotype
      relationships strongly support a role for a continuum of CAG length-dependent
      changes. The compendium of HTT CAG length-gene expression level relationships
      found at the HD CAGnome now provides convenient routes for discovery of
      candidates influenced by the HD mutation.

PMID- 24751920
TI  - Homocysteine-lowering therapy and risk of recurrent stroke, myocardial infarction
      and death: the impact of age in the VISP trial.
AB  - BACKGROUND: Clinical trials have failed to show a benefit of B vitamin therapy in
      reducing composite outcomes of cardiovascular death, myocardial infarction, and
      stroke among stroke survivors with elevated total serum homocysteine (tHcy)
      levels. Recent post hoc analyses have shown that numerous factors including age,
      baseline tHcy levels, folic acid fortification of grains, B12 status, renal
      function, comorbidities, and medications may modify the effect of B vitamin
      therapy on vascular risk in individuals with high tHcy. It remains possible that
      tHcy-lowering therapy may reduce cardiovascular risk in certain subgroups of
      stroke survivors. Post hoc subgroup analysis of the Heart Outcomes Prevention
      Evaluation-2 randomized controlled trial, which randomized participants with
      known cardiovascular disease to tHcy-lowering therapy or placebo, revealed larger
      treatment benefit for patients aged younger than 69 years; however, that analysis
      did not control for other factors. The aim of this study was to determine the
      effect of age on the impact of tHcy-lowering therapy for reducing vascular risk
      after stroke while controlling for other factors known to modify the effect of
      tHcy and tHcy-lowering therapy on vascular risk. METHODS: In this post hoc
      analysis of the Vitamin Intervention for Stroke Prevention (VISP) trial, a
      randomized controlled trial of tHcy lowering for secondary stroke prevention, we
      excluded individuals who had poor renal function (glomerular filtration rate <47;
      the 10th percentile) or were treated with vitamin B12 injections. We assessed the
      effects of high-dose vitamin replacement on primary (stroke, myocardial
      infarction, or death) and secondary (stroke) outcomes, after stratifying by age
      (< vs. >= median age, 67 years) and adjusting for demographic and clinical
      factors. RESULTS: This subgroup consisted of 2,993 individuals. Among individuals
      older than 67 years, high-dose vitamin therapy was associated with reduced risk
      of stroke, myocardial infarction or death (adjusted HR 0.76, 95% CI 0.58-0.99)
      and a trend towards reduced likelihood of stroke (adjusted HR 0.86, 95% CI 0.59
      1.25). High-dose vitamin therapy did not impact outcomes among individuals
      younger than 67 years. CONCLUSIONS: In this post hoc subgroup analysis of the
      VISP trial, age modified the association between B vitamin therapy and recurrent
      vascular risk among stroke survivors with elevated serum tHcy levels. Older
      individuals with stroke were more likely to benefit from B vitamin therapy than
      younger individuals. These findings can help inform the future design of clinical
      trials of tHcy-lowering therapy for cardiovascular risk reduction after stroke.
      (c) 2014 S. Karger AG, Basel.

PMID- 24751921
TI  - Interferon-lambda in the context of viral infections: production, response and
      therapeutic implications.
AB  - Interferon (IFN)-lambda forms the type III IFN family. Although they signal
      through distinct receptors, type I (IFN-alpha/beta) and type III IFNs elicit
      remarkably similar responses in cells. However, in vivo, type III and type I IFN
      responses are not fully redundant as their respective contribution to the
      antiviral defense highly depends on virus species. IFN-lambda is much more potent
      than IFN-alpha/beta at controlling rotavirus infection. In contrast, clearance of
      several other viruses, such as influenza virus, mostly depends on IFN-alpha/beta.
      The IFN-lambda receptor was reported to be preferentially expressed on epithelial
      cells. Cells responsible for IFN-lambda production are still poorly characterized
      but seem to overlap only partly IFN-alpha/beta-producing cells. Accumulating data
      suggest that epithelial cells are also important IFN-lambda producers. Thus, IFN
      lambda may primarily act as a protection of mucosal entities, such as the lung,
      skin or digestive tract. Type I and type III IFN signal transduction pathways
      largely overlap, and cross talk between these IFN systems occurs. Finally, this
      review addresses the potential benefit of IFN-lambda use for therapeutic purposes
      and summarizes recent results of genome-wide association studies that identified
      polymorphisms in the region of the IFN-lambda3 gene impacting on the outcome of
      treatments against hepatitis C virus infection.

PMID- 24751922
TI  - N-Terminal region is responsible for chemotaxis-inducing activity of flounder IL
      8.
AB  - The objective of this study was to locate the functional region responsible for
      the chemotaxis-inducing activity of flounder interleukin 8 (IL-8), which lacks
      the glutamic acid-leucine-arginine (ELR) motif essential for the induction of
      neutrophil migration by mammalian IL-8. Using a human cell line, we produced a
      secretory recombinant protein of flounder IL-8, and analyzed its chemotaxis
      inducing activity on leukocytes collected from the flounder kidney. The
      recombinant IL-8 induced significant migration in neutrophils, which were
      morphologically and functionally characterized. Using the Edman degradation
      method, the N-terminal amino acid sequence of rIL-8 was identified as VSLRSLGV.
      To examine the significance of the N-terminal region for the bioactivity of
      flounder IL-8, we prepared several recombinant proteins that containing mutations
      at the N-terminus. Modification of three residues (residues 9-11: serine-leucine
      histidine) corresponding in position to the ELR motif in mammalian IL-8 did not
      reduce its chemotaxis-inducing activity. However, deletion of the first six or
      more residues significantly reduced its chemotaxis-inducing activity. We propose
      that residue 6 (leucine) at the N-terminus is important for the chemotaxis
      inducing activity of flounder IL-8. 

PMID- 24751923
TI  - Effect of choline on antioxidant defenses and gene expressions of Nrf2 signaling
      molecule in the spleen and head kidney of juvenile Jian carp (Cyprinus carpio
      var. Jian).
AB  - The present work evaluates the effects of various levels of dietary choline on
      antioxidant defenses and gene expressions of Nrf2 signaling molecule in spleen
      and head kidney of juvenile Jian carp (Cyprinus carpio var. Jian). Fish were fed
      with six different experimental diets containing graded levels of choline at 165
      (choline-deficient control), 310, 607, 896, 1167 and 1820 mg kg(-1) diet for 65
      days. At the end of the feeding trail, fish were challenged with Aeromonas
      hydrophila and mortalities were recorded over 17 days. Dietary choline
      significantly decreased malondialdehyde and protein carbonyl contents in spleen
      and head kidney. However, anti-superoxide anion and anti-hydroxyl radical
      activities in spleen and head kidney also decreased. Interestingly, activities of
      superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx),
      glutathione-S-transferase (GST) and glutathione reductase (GR) in spleen, GPx
      activity in head kidney, and glutathione contents in spleen and head kidney were
      decreased with increase of dietary choline levels up to a certain point, whereas,
      activities of SOD, GST and GR in head kidney showed no significantly differences
      among groups. Similarly, expression levels of CuZnSOD, MnSOD, CAT, GPx1a, GPx1b
      and GR gene in spleen and head kidney were significantly lower in group with
      choline level of 607 mg kg(-1) diet than those in the choline-deficient group.
      The relative gene expressions of Nrf2 in head kidney and Keap1a in spleen and
      head kidney were decreased with increasing of dietary choline up to a certain
      point. However, the relative gene expression of Nrf2 in spleen were not
      significantly affected by dietary choline. In conclusion, dietary choline
      decreased the oxidant damage and regulated the antioxidant system in immune
      organs of juvenile Jian carp. 

PMID- 24751924
TI  - Effect of heparin on prevention of flap loss in microsurgical free flap transfer:
      a meta-analysis.
AB  - The effectiveness of heparin for thromboprophylaxis during microvascular free
      flap transfer is uncertain. The purpose of this meta-analysis was to determine
      the effect of heparin on the prevention of flap loss in microsurgical free flap
      transfer.A search of PubMed, Cochrane databases, and Google Scholar using
      combinations of the search terms heparin, free flap, flap loss, free tissue
      transfer was conducted on March 15, 2013. Inclusion criteria were: 1) Prospective
      randomized trials. 2) Retrospective, non-randomized studies. 3) Patients received
      free tissue transfer. Flap loss rate was used to evaluate treatment efficacy.
      Odds ratios (ORs) with 95% confidence intervals (CI) were calculated and compared
      between therapies. Four studies meet the criteria for analysis and were included.
      Two studiescompared aspirin and heparin, and the ORs of the 2 studies were 1.688
      and 2.087. The combined OR of 2.003 (95% CI 0.976-4.109, p = 0.058) did not
      indicate any significant difference between heparin and aspirin therapies. Two
      studiescompared high and low doses of dalteparin/heparin therapies, and the ORs
      of the 2 studies were 4.691 and 11.00. The combined OR of 7.810 (95% CI 1.859
      32.808, p = 0.005) revealed a significant difference indicating that high dose
      dalteparin or heparin therapy is associated with a greater flap loss rate than
      low dose therapy. Heparin and aspirin prophylaxis are associated with similar
      flap loss rates after free flap transfer, and high dose dalteparin or heparin
      therapy is associated with a greater flap loss rate than low dose therapy. 

PMID- 24751925
TI  - Meta-analysis of association between the -2578C/A polymorphism of the vascular
      endothelial growth factor and retinopathy in type 2 diabetes in Asians and
      Caucasians.
AB  - BACKGROUND AND OBJECTIVES: Vascular endothelial growth factor (VEGF) has been
      shown to play an important role in the development and progress of diabetic
      retinopathy (DR). A number of case-control studies focused on the association
      between VEGF -2578C/A and risk for DR. But the results were not always
      consistent, so we performed a meta-analysis to evaluate the precise association
      between this variant and risk for DR. METHODS: All publications on the
      association between VEGF -2578C/A polymorphism and DR were searched in the
      following electronic databases: PubMed, Embase, the Cochrane Library and Chinese
      Biomedical Literature Database, with the last report up to January 2013. This
      meta-analysis was assessed by Review Manager 5.1. RESULTS: A total of 6 studies
      were involved in this meta-analysis, including 835 cases and 867 controls.
      Overall, we found a significant association between this polymorphism and DR (A
      vs. C: OR=1.49, 95% CI=1.26-1.77, p<0.00001; AA vs. CA+CC: OR=1.26, 95% CI=0.94
      1.68, p=0.12; AA+CA vs. CC: OR=1.56, 95% CI=1.27-1.91, p<0.00001; AA vs. CC:
      OR=1.67, 95% CI=1.20-2.32, p=0.003; CA vs. CC: OR=1.51, 95% CI=1.21-1.87,
      p=0.0002), but we did not find any significant association in Caucasians in
      subgroup analysis. The results were not materially altered after the studies
      which did not fulfill the Hardy-Weinberg equilibrium were excluded. CONCLUSION:
      Our meta-analysis supports the association between the VEGF -2578C/A polymorphism
      and DR, but not in the Caucasian population.

PMID- 24751926
TI  - Clinicopathological characteristics of laterally spreading colorectal tumor.
AB  - BACKGROUND AND AIMS: Laterally spreading tumor (LST) is a colorectal pre
      cancerous lesion. Previous studies have demonstrated distinct LST
      clinicopathological characteristics in different populations. This study
      evaluated clinicopathological characteristics of LST in a Chinese population.
      METHODS: A total of 259 Chinese LST patients with 289 lesions were recruited for
      endoscopic and clinicopathological analyses. RESULTS: Among these 289 lesions,
      185 were granular type (LST-G), whereas 104 were non-granular type (LST-NG). LST
      G lesions were further classified into homogeneous G-type and nodular mixed G
      type, while LST-NG lesions were further classified into flat elevated NG-type and
      pseudo-depressed NG-type. Clinically, these four LST subtypes showed distinct
      clinicopathological characteristics, e.g., lesion size, location, or
      histopathological features (high-grade intraepithelial neoplasia and submucosal
      carcinoma). The nodular mixed G-type showed larger tumor size and higher
      incidence of high-grade intraepithelial neoplasia compared to the other three
      subtypes, while pseudo-depressed NG-type lesions showed the highest incidence of
      submucosal carcinoma. Noticeably, no diffidence was detected between the lesions
      of homogeneous G-type and flat elevated NG-type with regard to the
      histopathological features. Histology of the malignancy potential was associated
      with nodular mixed G-type [OR = 2.41, 95% CI (1.09-5.29); P = 0.029], flat
      elevated NG-type [OR = 3.49, 95% CI (1.41-8.22); P = 0.007], Diameter >=30 mm [OR
      = 2.56, 95% CI (1.20-5.20); P = 0.009], Villous adenoma [OR = 2.76, 95% CI (1.01
      7.58); P = 0.048] and serrated adenoma [OR = 6.99, 95% CI (1.81-26.98); P =
      0.005]. CONCLUSION: Chinese LSTs can be divided into four different subtypes,
      which show distinct clinicopathological characteristics. Morphology, size and
      pathological characteristics are all independent predictors of advanced
      histology.

PMID- 24751928
TI  - Optimal control for predicting customized drug dosage for superovulation stage of
      in vitro fertilization.
AB  - in vitro fertilization (IVF) is one of the most highly pursued assisted
      reproductive technologies (ART) worldwide. IVF procedure is divided into four
      stages: Superovulation, Egg-retrieval, Insemination/Fertilization and Embryo
      transfer. Among these superovulation is the most crucial stage since it involves
      external injection of hormones to stimulate development and maturation of
      multiple follicles or oocytes. Although numerous advancements have been made in
      IVF procedures, little attention has been given to modifying the existing
      protocols based on a 'patient specific' predictive model. A model for follicle
      growth and number change as a function of the injected hormones and patient
      characteristics has been developed and validated for data available on 50
      superovulation cycles. The model has 9 patient specific parameters which can be
      determined from the initial 2 days of observation and can help in projecting the
      superovulation outcome for the ongoing cycle. Based on this model, the dosage of
      the hormones to stimulate multiple ovulation or follicle growth is predicted by
      using the theory of optimal control. The objective of successful superovulation
      is to obtain maximum number of mature oocytes/follicles within a particular size
      range. Using the mathematical model of follicle growth dynamics and optimal
      control theory, optimal dose and frequency of medication customized for each
      patient (n=5) is predicted for obtaining the desired result. The results indicate
      a better final day follicle size distribution when the dosage of the hormones is
      varied by some amounts as compared to the actual dosage given to the patient in
      the existing cycles. This ensures a better success rate for the superovulation
      cycles and reduces the costs of excess medication and daily monitoring. The idea
      is to provide the medical practitioners with a guideline for planned treatment,
      for a procedure currently based on trial and error in order to get better success
      rates. 

PMID- 24751929
TI  - Energetic arguments predict larger-bodied animals will be increasingly confined
      to flat environments.

PMID- 24751930
TI  - A mathematical approach to emergent properties of metabolic networks: partial
      coupling relations, hyperarcs and flux ratios.
AB  - Emergent properties in systems biology are those which arise only when the
      biological system passes a certain level of complexity. In this study, we
      introduce some of the emergent properties which appear in the constraint-based
      analysis of metabolic networks. These properties generally appear as a result of
      existence of hfdeyperarcs and irreversible reactions in networks. Here, we
      present examples of metabolic networks in which there exist at least two
      reactions whose fluxes cannot be written as products and/or ratios of the
      stoichiometric coefficients of the network. We show that any such network
      contains at least one hyperarc. Additionally, we prove that partial coupling
      cannot appear in consistent metabolic networks with less than four reactions, or
      with less than three irreversible reactions, or without hyperarc(s). 

PMID- 24751927
TI  - The effect of interstitial pressure on therapeutic agent transport: coupling with
      the tumor blood and lymphatic vascular systems.
AB  - Vascularized tumor growth is characterized by both abnormal interstitial fluid
      flow and the associated interstitial fluid pressure (IFP). Here, we study the
      effect that these conditions have on the transport of therapeutic agents during
      chemotherapy. We apply our recently developed vascular tumor growth model which
      couples a continuous growth component with a discrete angiogenesis model to show
      that hypertensive IFP is a physical barrier that may hinder vascular
      extravasation of agents through transvascular fluid flux convection, which drives
      the agents away from the tumor. This result is consistent with previous work
      using simpler models without blood flow or lymphatic drainage. We consider the
      vascular/interstitial/lymphatic fluid dynamics to show that tumors with larger
      lymphatic resistance increase the agent concentration more rapidly while also
      experiencing faster washout. In contrast, tumors with smaller lymphatic
      resistance accumulate less agents but are able to retain them for a longer time.
      The agent availability (area-under-the curve, or AUC) increases for less
      permeable agents as lymphatic resistance increases, and correspondingly decreases
      for more permeable agents. We also investigate the effect of vascular pathologies
      on agent transport. We show that elevated vascular hydraulic conductivity
      contributes to the highest AUC when the agent is less permeable, but to lower AUC
      when the agent is more permeable. We find that elevated interstitial hydraulic
      conductivity contributes to low AUC in general regardless of the transvascular
      agent transport capability. We also couple the agent transport with the tumor
      dynamics to simulate chemotherapy with the same vascularized tumor under
      different vascular pathologies. We show that tumors with an elevated interstitial
      hydraulic conductivity alone require the strongest dosage to shrink. We further
      show that tumors with elevated vascular hydraulic conductivity are more hypoxic
      during therapy and that the response slows down as the tumor shrinks due to the
      heterogeneity and low concentration of agents in the tumor interior compared with
      the cases where other pathological effects may combine to flatten the IFP and
      thus reduce the heterogeneity. We conclude that dual normalizations of the
      micronevironment - both the vasculature and the interstitium - are needed to
      maximize the effects of chemotherapy, while normalization of only one of these
      may be insufficient to overcome the physical resistance and may thus lead to sub
      optimal outcomes. 

PMID- 24751932
TI  - Lipoprotein(a) metabolism.
AB  - PURPOSE OF REVIEW: Lipoprotein(a) [Lp(a)] is an atherogenic lipoprotein. The
      metabolism of this lipoprotein is still not well understood. RECENT FINDINGS: It
      has long been known that the plasma concentration of Lp(a) is highly heritable,
      with its genetic determinants located in the apo(a) locus and regulating the rate
      of hepatic apo(a) production. Recent human intervention trials have convincingly
      established that, in addition to apo(a) production, hepatic apoB100 production
      plays an important role in Lp(a) levels. Although the major site and mode of
      Lp(a) clearance remain unidentified, a recent cell and animal study points to the
      involvement of the hepatic scavenger receptor class B type I in the uptake of
      both the lipid and protein constituents of Lp(a) from plasma. SUMMARY: Progress
      in the understanding of Lp(a) metabolism has the potential to lead to the
      development of novel and specific treatments for the reduction of Lp(a) levels
      and the associated risk of cardiovascular disease.

PMID- 24751931
TI  - Hypobetalipoproteinemia and abetalipoproteinemia.
AB  - PURPOSE OF REVIEW: Several mutations in the apoB, proprotein convertase
      subtilisin/kexin type 9 (PCSK9), and MTP genes result in low or absent levels of
      apoB and LDL-cholesterol in plasma, which cause familial hypobetalipoproteinemia
      and abetalipoproteinemia. Mutations in the ANGPTL3 gene cause familial combined
      hypolipidemia. Clinical manifestations range from none to severe, debilitating,
      and life-threatening disorders. This review summarizes recent genetic, metabolic,
      and clinical findings and presents an update on management strategies. RECENT
      FINDINGS: Cases of cirrhosis and hepatocellular carcinoma have now been
      identified in heterozygous familial hypobetalipoproteinemia probably because of
      decreased triglyceride transport capacity from the liver. ANGPTL3 mutations cause
      low levels of LDL-cholesterol and low HDL-cholesterol in compound heterozygotes
      and homozygous individuals, decrease reverse cholesterol transport, and lower
      glucose levels. The effect on atherosclerosis is unknown; however, severe fatty
      liver has been identified. Loss-of-function mutations in PCSK9 cause familial
      hypobetalipoproteinemia, which appears to lower risk for coronary artery disease
      and has no adverse sequelae. Phase III clinical trials are now underway examining
      the effect of PCSK9 inhibitors on cardiovascular events in combination with
      statin drugs. SUMMARY: Mutations causing low LDL-cholesterol and apoB have
      provided insight into lipid metabolism, disease associations, and the basis for
      drug development to lower LDL-cholesterol in disorders causing high levels of
      cholesterol. Early diagnosis and treatment are necessary to prevent adverse
      sequelae from familial hypobetalipoproteinemia and abetalipoproteinemia.

PMID- 24751933
TI  - Intestinal lipid absorption and lipoprotein formation.
AB  - PURPOSE OF REVIEW: To summarize the evidence for the presence of two lipid
      absorption pathways and their regulation. RECENT FINDINGS: Lipid absorption
      involves hydrolysis of dietary fat in the lumen of the intestine, followed by the
      uptake of hydrolyzed products by enterocytes. Lipids are resynthesized in the
      endoplasmic reticulum and are either secreted with chylomicrons and HDLs or
      stored as cytoplasmic lipid droplets. Lipids in the droplets are hydrolyzed and
      are secreted at a later time. Secretion of lipids by the chylomicron and HDL
      pathways are dependent on microsomal triglyceride transfer protein (MTP) and ATP
      binding cassette family A protein 1, respectively, and are regulated
      independently. Gene-ablation studies showed that MTP function and chylomicron
      assembly is essential for the absorption of triglycerides. Ablation of MTP
      abolishes triglyceride absorption and results in massive triglyceride
      accumulation in enterocytes. Although the majority of phospholipid, cholesterol,
      and vitamin E are absorbed through the chylomicron pathway, a significant amount
      of these lipids are also absorbed via the HDL pathway. Chylomicron assembly and
      secretion is increased by the enhanced availability of fatty acids, whereas the
      HDL pathway is upregulated by liver X receptor agonists. SUMMARY: Triglycerides
      are exclusively transported with chylomicrons and this process is critically
      dependent on MTP. In addition to chylomicrons, absorption of phospholipids, free
      cholesterol, retinol, and vitamin E also involves HDLs. These two pathways are
      complementary and are regulated independently. They may be targeted to lower
      lipid absorption in order to control hyperlipidemia, obesity, metabolic syndrome,
      steatosis, insulin resistance, atherosclerosis, and other disorders.

PMID- 24751934
TI  - Structural order in Pannexin 1 cytoplasmic domains.
AB  - Pannexin 1 forms ion and metabolite permeable hexameric channels with abundant
      expression in the central nervous system and elsewhere. Although pannexin 1 does
      not form intercellular channels, a common channel topology and oligomerization
      state, as well as involvement of the intracellular carboxyl terminal (CT) domain
      in channel gating, is shared with connexins. In this study, we characterized the
      secondary structure of the mouse pannexin 1 cytoplasmic domains to complement
      structural studies of the transmembrane segments and compare with similar domains
      from connexins. A combination of structural prediction tools and circular
      dichroism revealed that, unlike connexins (predominately intrinsically
      disordered), cytosolic regions of pannexin 1 contain approximately 50% secondary
      structure, a majority being alpha-helical. Moreover, prediction of transmembrane
      domains uncovered a potential membrane interacting region (I360-G370) located
      upstream of the caspase cleavage site (D375-D378) within the pannexin 1 CT
      domain. The alpha-helical content of a peptide containing these domains (G357
      S384) increased in the presence of detergent micelles providing evidence of
      membrane association. We also purified a pannexin 1 CT construct containing the
      caspase cleavage site (M374-C426), assigned the resonances by NMR, and confirmed
      cleavage by Caspase-3 in vitro. On the basis of these structural studies of the
      cytoplasmic domains of pannexin 1, we propose a mechanism for the opening of
      pannexin 1 channels upon apoptosis, involving structural changes within the CT
      domain. 

PMID- 24751936
TI  - Residents'corner April 2014. DeRmpath & Clinic: differential diagnosis of two
      psoriasiform dermatoses.

PMID- 24751935
TI  - Functional near infrared spectroscopy (fNIRS) to assess cognitive function in
      infants in rural Africa.
AB  - Cortical mapping of cognitive function during infancy is poorly understood in low
      income countries due to the lack of transportable neuroimaging methods. We have
      successfully piloted functional near infrared spectroscopy (fNIRS) as a
      neuroimaging tool in rural Gambia. Four-to-eight month old infants watched videos
      of Gambian adults perform social movements, while haemodynamic responses were
      recorded using fNIRS. We found distinct regions of the posterior superior
      temporal and inferior frontal cortex that evidenced either visual-social
      activation or vocally selective activation (vocal > non-vocal). The patterns of
      selective cortical activation in Gambian infants replicated those observed within
      similar aged infants in the UK. These are the first reported data on the
      measurement of localized functional brain activity in young infants in Africa and
      demonstrate the potential that fNIRS offers for field-based neuroimaging research
      of cognitive function in resource-poor rural communities. 

PMID- 24751938
TI  - How does stress possibly affect cardiac remodeling?
AB  - The aim of this study was to evaluate the predictive value of adrenocorticotropic
      hormone (ACTH), cortisol and ACTH receptor polymorphism (ACTHRP) for left
      ventricular (LV) remodeling. Thirty-six elite male athletes, as chronic stress
      adaptation models, and twenty sedentary age and sex-mached subjects emabarked on
      standard and tissue Doppler echocardiography to assess cardiac parameters at
      rest. They performed maximal cardiopulmonary test, which was used as an acute
      stress model. ACTH and cortisol were measured at rest (10min before test), at
      beginning, at maximal effort, at 3rd min of recovery, using radioimmunometric and
      radioimmunoassey techniques, respectively. Promoter region of ACTHR gene
      (18p11.2) was analysed from blood samples using reverse polymerization reaction
      with the analysis of restriction fragment length polimorphisam by SacI
      restriction enzyme. Normal genotype was CTC/CTC, heterozygot for ACTHRP CTC/CCC
      and homozygot CCC/CCC. In all participants, ACTH and cortisol increased during
      acute stress, whereas in recovery ACTH increased and cortisol remained unchanged.
      49/56 examiners manifested CTC/CTC, 7/56 CTC/CCC and 0/56 CCC/CCC. There was no
      difference in ACTHRP frequency between groups (chi(1)(2)=0.178, p=0.67). LV mass
      (LVM) and LV end-diastolic volume (LVVd) were higher in athletes than in controls
      (p<0.01) and lower in CTC/CTC than in CTC/CCC genotype (219.43+/-46.59(SD)g vs.
      276.34+/-48.86(SD)g, p=0.004; 141.24+/-24.46(SD)ml vs. 175.29+/-37.07(SD)ml,
      p=0.002; respectively). In all participants, predictors of LVM and LVVd were ACTH
      at rest (B=-1.00,-0.44; beta=-0.30,-0.31; p=0.026,0.012, respectively) and ACTHRP
      (B=56.63,34; beta=0.37,0.40; p=0.003,0.001, respectively). These results
      demonstrate that ACTH and ACTHRP strongly predict cardiac morphology suggesting
      possible regulatory role of stress system activity and sensitivity in cardiac
      remodeling. 

PMID- 24751937
TI  - Profiling hepatic microRNAs in zebrafish: fluoxetine exposure mimics a fasting
      response that targets AMP-activated protein kinase (AMPK).
AB  - This study examined the similarities in microRNA profiles between fasted and
      fluoxetine (FLX) exposed zebrafish and downstream target transcripts and
      biological pathways. Using a custom designed microarray targeting 270 zebrafish
      miRNAs, we identified 9 differentially expressed miRNAs targeting transcripts in
      biological pathways associated with anabolic metabolism, such as adipogenesis,
      cholesterol biosynthesis, triacylglycerol synthesis, and insulin signaling.
      Exposure of female zebrafish to 540 ng/L FLX, an environmentally relevant
      concentration and a known metabolic repressor, increased specific miRNAs
      indicating greater inhibition of these pathways in spite of continued feeding.
      Further examination revealed two specific miRNAs, dre-let-7d and dre-miR-140-5p,
      were predicted in silico to bind to a primary regulator of metabolism, adenosine
      monophosphate-activated protein kinase (AMPK), and more specifically the two
      isoforms of the catalytic subunit, AMPKalpha1 and alpha2, respectively. Real-time
      analysis of the relative transcript abundance of the alpha1 and alpha2 mRNAs
      indicated a significant inverse relationship between specific miRNA and target
      transcript. This suggests that AMPK-related pathways may be compromised during
      FLX exposure as a result of increased miRNA abundance. The mechanism by which FLX
      regulates miRNA abundance is unknown but may be direct at the liver. The
      serotonin transporter, slc6a4, is the target of FLX and other selective serotonin
      reuptake inhibitors (SSRI) and it was found to be expressed in the liver,
      although treatment did not alter expression of this transporter. Exposure to FLX
      disrupts key hepatic metabolic pathways, which may be indicative of reduced
      overall fitness and these effects may be linked to specific miRNA abundance. This
      has important implications for the heath of fish because concentrations of SSRIs
      in aquatic ecosystems are continually increasing. 

PMID- 24751939
TI  - Fever.

PMID- 24751940
TI  - A non-climacteric fruit gene CaMADS-RIN regulates fruit ripening and ethylene
      biosynthesis in climacteric fruit.
AB  - MADS-box genes have been reported to play a major role in the molecular circuit
      of developmental regulation. Especially, SEPALLATA (SEP) group genes play a
      central role in the developmental regulation of ripening in both climacteric and
      non-climacteric fruits. However, the mechanisms underlying the regulation of SEP
      genes to non-climacteric fruits ripening are still unclear. Here a SEP gene of
      pepper, CaMADS-RIN, has been cloned and exhibited elevated expression at the
      onset of ripening of pepper. To further explore the function of CaMADS-RIN, an
      overexpressed construct was created and transformed into ripening inhibitor (rin)
      mutant tomato plants. Broad ripening phenotypes were observed in CaMADS-RIN
      overexpressed rin fruits. The accumulation of carotenoid and expression of PDS
      and ZDS were enhanced in overexpressed fruits compared with rin mutant. The
      transcripts of cell wall metabolism genes (PG, EXP1 and TBG4) and lipoxygenase
      genes (TomloxB and TomloxC) accumulated more abundant compared to rin mutant.
      Besides, both ethylene-dependent genes including ACS2, ACO1, E4 and E8 and
      ethylene-independent genes such as HDC and Nor were also up-regulated in
      transgenic fruits at different levels. Moreover, transgenic fruits showed
      approximately 1-3 times increase in ethylene production compared with rin mutant
      fruits. Yeast two-hybrid screen results indicated that CaMADS-RIN could interact
      with TAGL1, FUL1 and itself respectively as SlMADS-RIN did in vitro. These
      results suggest that CaMADS-RIN affects fruit ripening of tomato both in ethylene
      dependent and ethylene-independent aspects, which will provide a set of
      significant data to explore the role of SEP genes in ripening of non-climacteric
      fruits. 

PMID- 24751941
TI  - Robustness analysis of stochastic biochemical systems.
AB  - We propose a new framework for rigorous robustness analysis of stochastic
      biochemical systems that is based on probabilistic model checking techniques. We
      adapt the general definition of robustness introduced by Kitano to the class of
      stochastic systems modelled as continuous time Markov Chains in order to
      extensively analyse and compare robustness of biological models with uncertain
      parameters. The framework utilises novel computational methods that enable to
      effectively evaluate the robustness of models with respect to quantitative
      temporal properties and parameters such as reaction rate constants and initial
      conditions. We have applied the framework to gene regulation as an example of a
      central biological mechanism where intrinsic and extrinsic stochasticity plays
      crucial role due to low numbers of DNA and RNA molecules. Using our methods we
      have obtained a comprehensive and precise analysis of stochastic dynamics under
      parameter uncertainty. Furthermore, we apply our framework to compare several
      variants of two-component signalling networks from the perspective of robustness
      with respect to intrinsic noise caused by low populations of signalling
      components. We have successfully extended previous studies performed on
      deterministic models (ODE) and showed that stochasticity may significantly affect
      obtained predictions. Our case studies demonstrate that the framework can provide
      deeper insight into the role of key parameters in maintaining the system
      functionality and thus it significantly contributes to formal methods in
      computational systems biology. 

PMID- 24751942
TI  - Efficacy of IFN-lambda1 to protect human airway epithelial cells against human
      rhinovirus 1B infection.
AB  - Impaired interferon (IFN) production has been observed in various obstructive
      respiratory diseases. This contributes to enhanced sensitivity towards viral
      infections triggering acute exacerbations. To compensate for this impaired host
      IFN response, there is need to explore new therapeutic strategies, like exogenous
      administration of IFNs as prophylactic treatment. In the present study, we
      examined the protective potential of IFN-lambda1 and compared it with the
      previously established protecting effect of IFN-beta. A549 cells and human
      primary bronchial epithelial cells were first treated with either IFN-beta (500
      IU/ml) or IFN-lambda1 (500 ng/ml) for 18 h. For infection, two approaches were
      adopted: i) Continuous scenario: after pre-treatment, cells were infected
      immediately for 24 h with human rhinovirus 1B (HRV1B) in IFN-containing medium,
      or were cultured for another 72 h in IFN-containing medium, and then infected for
      24 h with HRV1B, ii) Pre-treatment scenario: IFN-containing medium was replaced
      after 18 h and cells were infected for 4 h either immediately after pre-treatment
      or after additional culturing for 72 h in IFN-free medium. The protective effect
      was evaluated in terms of reduction in the number of viral copies/infectious
      progeny, and enhanced expression of IFN-stimulated genes (ISGs). In both cell
      types and in both approaches, IFN-lambda1 and IFN-beta treatment resulted in
      pronounced and long-lasting antiviral effects exemplified by significantly
      reduced viral copy numbers and diminished infectious progeny. This was associated
      with strong up-regulation of multiple ISGs. However, in contrast to the IFN-beta
      induced expression of ISGs, which decreased over time, expression of ISGs induced
      by IFN-lambda1 was sustained or even increased over time. Here we demonstrate
      that the protective potential of IFN-lambda1 is comparable to IFN-beta. Yet, the
      long-lasting induction of ISGs by IFN-lambda1 and most likely less incitement of
      side effects due to more localized expression of its receptors could make it an
      even more promising candidate for prophylactic treatment than IFN-beta. 

PMID- 24751943
TI  - [Onychomycosis mycological profile in Abidjan (Cote d'Ivoire)].
AB  - AIM OF THE STUDY: The epidemiological profile of onychomycosis is poorly
      determined in Cote d'Ivoire. This study aimed to determine the fungal aetiologies
      of these onychomycosis in Abidjan. PATIENTS AND METHODS: This cross-sectional
      study was conducted from February to August 2011 at the Department of Dermatology
      of the University Hospital of Treichville. All patients who consulted for
      onycholysis were interviewed. All samples were analyzed by direct examination and
      Sabouraud-chloramphenicol and Sabouraud-chloramphenicol-actidione culture was
      performed. Species identification was based on microscopic characteristics of the
      fungus observed. RESULTS: A total of 53 patients were included. The prevalence of
      onychomycosis was estimated at 66%. The unilateral lesions were statistically
      different from bilateral lesions (P=0.010). Women were more affected at the hands
      than men (P=0.010). Five species of yeasts and two dermatophytes species were
      identified. Yeasts species were essentially Candida tropicalis (36.4%) and
      Candida albicans (30.3%). Trichophyton rubrum and Trichophyton soudanense were
      the only dermatophytes isolated. No contributing factors were statistically
      related to the occurrence of onychomycosis in our series. CONCLUSION: The
      observed onychomycosis in Cote d'Ivoire are mainly caused by yeasts. Although in
      our series the risk factors have not been identified, hygiene of the nails should
      provide effective prevention.

PMID- 24751944
TI  - Systemic sclerosis with normal or nonspecific nailfold capillaroscopy.
AB  - BACKGROUND: In systemic sclerosis (SSc), a specific nailfold videocapillaroscopy
      (NVC) pattern is observed in 90% of cases and seems to be associated with
      severity and progression of the disease. OBJECTIVE: To describe the
      characteristics of SSc patients with normal or nonspecific (normal/nonspecific)
      NVC. METHODS: In a retrospective cohort study, clinical features and visceral
      involvements of 25 SSc cases with normal/nonspecific NVC were compared to 63 SSc
      controls with the SSc-specific NVC pattern. RESULTS: Normal/nonspecific NVC
      versus SSc-specific NVC pattern was significantly associated with absence of skin
      sclerosis (32 vs. 6.3%, p = 0.004), absence of telangiectasia (47.8 vs. 17.3%, p
      = 0.006) and absence of sclerodactyly (60 vs. 25.4%, p = 0.002), and less
      frequent severe pulmonary involvement (26.3 vs. 58.2%, p = 0.017). CONCLUSION:
      Normal/nonspecific NVC in SSc patients appears to be associated with less severe
      skin involvement and less frequent severe pulmonary involvement.

PMID- 24751945
TI  - Protection against ovariectomy-induced bone loss by tranilast.
AB  - BACKGROUND: Tranilast (N-(3',4'-dimethoxycinnamonyl) anthranilic acid) has been
      shown to be therapeutically effective, exerting anti-inflammatory and anti
      oxidative effects via acting on macrophage. We hypothesized that Tranilast may
      protect against oxidative stress-induced bone loss via action in osteoclasts
      (OCs) that shares precursors with macrophage. METHODOLOGY AND PRINCIPAL FINDINGS:
      To elucidate the role of Tranilast, ovariectomy (OVX)-induced bone loss in vivo
      and OC differentiation in vitro were evaluated by uCT and tartrate-resistant acid
      phosphatase staining, respectively. Oral administration of Tranilast protected
      against OVX-induced bone loss with decreased serum level of reactive oxygen
      species (ROS) in mice. Tranilast inhibited OC formation in vitro. Decreased
      osteoclastogenesis by Tranilast was due to a defect of receptor activator of
      nuclear factor-kappaB ligand (RANKL) signaling, at least partly via decreased
      activation of nuclear factor-kappaB and reduced induction and nuclear
      translocation of nuclear factor of activated T cells, cytoplasmic 1 (or NFAT2).
      Tranilast also decreased RANKL-induced a long lasting ROS level as well as TGF
      beta to inhibit osteoclastogenesis. Reduced ROS caused by Tranilast was due to
      the induction of ROS scavenging enzymes (peroxiredoxin 1, heme oxygenase-1, and
      glutathione peroxidase 1) as well as impaired ROS generation.
      CONCLUSIONS/SIGNIFICANCE: Our data suggests the therapeutic potential of
      Tranilast for amelioration of bone loss and oxidative stress due to loss of
      ovarian function.

PMID- 24751946
TI  - Free radical scavenging, antioxidant and cancer chemoprevention by grape seed
      proanthocyanidin: an overview.
AB  - A large number of investigations have demonstrated a broad spectrum of
      pharmacological and therapeutic benefits of grape seed proanthocyanidins (GSP)
      against oxidative stress and degenerative diseases including cardiovascular
      dysfunctions, acute and chronic stress, gastrointestinal distress, neurological
      disorders, pancreatitis, various stages of neoplastic processes and
      carcinogenesis including detoxification of carcinogenic metabolites. GSP
      exhibited potent free radical scavenging abilities in both in vitro and in vivo
      models. GSP exerted significant in vivo protection against structurally diverse
      drug and chemical-induced hepatotoxicity, cardiotoxicity, neurotoxicity,
      nephrotoxicity and spleentoxicity. GSP also protected against idarubicin and 4
      hydroxyperoxy-cyclophosphamide-induced cytotoxicity toward human normal liver
      cells. GSP exhibited selective cytotoxicity toward selected human cancer cells,
      while enhancing the growth and viability of normal cells. GSP exhibited potent
      modulatory effects of pro-apoptotic and apoptotic regulatory bcl-XL, p53, c-myc,
      c-JUN, JNK-1 and CD36 genes. Long-term exposure to GSP may serve as a novel
      chemoprotectant against three stages of DMN-induced liver carcinogenesis and
      tumorigenesis including initiation, promotion and progression. GSP may
      selectively protect against oxidative stress, genomic integrity and cell death
      patterns in vivo. These results demonstrate that GSP may serve as a novel
      therapeutic intervention against carcinogenesis. 

PMID- 24751947
TI  - Dbx1 is a direct target of SOX3 in the spinal cord.
AB  - SoxB1 sub-family of transcriptional regulators are expressed in progenitor (NP)
      cells throughout the neuroaxis and are generally downregulated during neuronal
      differentiation. Gain- and loss-of-function studies indicate that Sox1, Sox2 and
      Sox3 are key regulators of NP differentiation and that their roles in CNS
      development are largely redundant. Nevertheless, mutation of each SoxB1
      individually results in a different array of CNS defects, raising the possibility
      that SoxB1 proteins have subtly different functions in NP cells. To explore the
      mechanism of SOXB1 functional redundancy, and to identify genes that are most
      sensitive to loss of the Sox3 gene, we performed genome wide expression profiling
      of Sox3 null NP cells. Nineteen genes with abnormal expression were identified,
      including the homeobox gene Dbx1. Analysis of Sox3 null embryos revealed that
      Dbx1 was significantly reduced in the neural tube and developing brain and that
      SOX3 bound directly to conserved elements associated with this gene in cultured
      NP cells and in vivo. These data define Dbx1 as a direct SOX3 target gene whose
      expression, intriguingly, is not fully rescued by other SOXB1 transcription
      factors, suggesting that there are inherent differences in SOXB1 protein
      activity. 

PMID- 24751949
TI  - Sunk costs in the human brain.
AB  - Rational decision-making should not be influenced by irrecoverable past costs.
      Human beings, however, often violate this basic rule of economics and take 'sunk'
      costs into account when making decisions about current or future investments,
      thus exhibiting a so-called 'sunk cost effect'. Although the sunk cost effect may
      have serious political, financial or personal consequences, its neural basis is
      largely unknown. Using functional magnetic resonance imaging (fMRI) and a novel
      financial decision-making task, we show here that previous investments reduced
      the contribution of the ventromedial prefrontal cortex (vmPFC) to current
      decision-making and that this reduction in vmPFC activity correlated with the
      sunk cost effect. Moreover, activity in the dorsolateral prefrontal cortex
      (dlPFC) was associated with the norm not to waste resources and negatively
      correlated with vmPFC activity. The present findings show how past investments
      may bias decision-making in the human brain, suggesting that the interaction of
      vmPFC and dlPFC may promote a tendency to throw good money after bad. 

PMID- 24751948
TI  - Regulator of G-protein signaling 19 (RGS19) and its partner Galpha-inhibiting
      activity polypeptide 3 (GNAI3) are required for zVAD-induced autophagy and cell
      death in L929 cells.
AB  - Autophagy has diverse biological functions and is involved in many biological
      processes. The L929 cell death induced by the pan-caspase inhibitor
      benzyloxycarbonyl-Val-Ala-Asp-(OMe)-fluoromethyl ketone (zVAD) was shown to be an
      autophagy-mediated death for which RIP1 and RIP3 were both required. It was also
      reported that zVAD can induce a small amount of TNF production, which was shown
      to be required for zVAD-induced L929 cell death, arguing for the contribution of
      autophagy in the zVAD-induced L929 cell death. In an effort to study RIP3
      mediated cell death, we identified regulator of G-protein signaling 19 (RGS19) as
      a RIP3 interacting protein. We showed that RGS19 and its partner Galpha
      inhibiting activity polypeptide 3 (GNAI3) are involved in zVAD-, but not TNF-,
      induced cell death. The role of RGS19 and GNAI3 in zVAD-induced cell death is
      that they are involved in zVAD-induced autophagy. By the use of small hairpin
      RNAs and chemical inhibitors, we further demonstrated that zVAD-induced autophagy
      requires not only RIP1, RIP3, PI3KC3 and Beclin-1, but also RGS19 and GNAI3, and
      this autophagy is required for zVAD-induced TNF production. Collectively, our
      data suggest that zVAD-induced L929 cell death is a synergistic result of
      autophagy, caspase inhibition and autocrine effect of TNF. 

PMID- 24751950
TI  - Plague is a human disease, caused by Yersinia pestis.

PMID- 24751951
TI  - "Using spectral-domain optical coherence tomography imaging to identify the
      presence of retinal silicone oil emulsification after silicone oil tamponade.".

PMID- 24751952
TI  - Reply: To PMID 23591533.

PMID- 24751953
TI  - Immunometabolism: IL-6, the resistance fighter.

PMID- 24751954
TI  - Development: we are what mum eats!

PMID- 24751955
TI  - Emergency granulopoiesis.
AB  - Neutrophils are a key cell type of the innate immune system. They are short-lived
      and need to be continuously generated in steady-state conditions from
      haematopoietic stem and progenitor cells in the bone marrow to ensure their
      immediate availability for the containment of invading pathogens. However, if
      microbial infection cannot be controlled locally, and consequently develops into
      a life-threatening condition, neutrophils are used up in large quantities and the
      haematopoietic system has to rapidly adapt to the increased demand by switching
      from steady-state to emergency granulopoiesis. This involves the markedly
      increased de novo production of neutrophils, which results from enhanced myeloid
      precursor cell proliferation in the bone marrow. In this Review, we discuss the
      molecular and cellular events that regulate emergency granulopoiesis, a process
      that is crucial for host survival. 

PMID- 24751957
TI  - Parasite immunity: protective teamwork.

PMID- 24751958
TI  - Psychological aspects of patients with intrinsic atopic dermatitis.

PMID- 24751956
TI  - Cytokines in inflammatory bowel disease.
AB  - Cytokines have a crucial role in the pathogenesis of inflammatory bowel diseases
      (IBDs), such as Crohn's disease and ulcerative colitis, where they control
      multiple aspects of the inflammatory response. In particular, the imbalance
      between pro-inflammatory and anti-inflammatory cytokines that occurs in IBD
      impedes the resolution of inflammation and instead leads to disease perpetuation
      and tissue destruction. Recent studies suggest the existence of a network of
      regulatory cytokines that has important implications for disease progression. In
      this Review, we discuss the role of cytokines produced by innate and adaptive
      immune cells, as well as their relevance to the future therapy of IBD. 

PMID- 24751959
TI  - An update on neuro-ophthalmology of multiple sclerosis: the visual system as a
      model to study multiple sclerosis.
AB  - PURPOSE OF REVIEW: The purpose of this review is to familiarize the reader with
      the landscape of current neuro-ophthalmology research in the field of multiple
      sclerosis and to highlight important findings, directions of future research and
      advances in the clinical management of visual and ocular motor manifestations of
      multiple sclerosis. RECENT FINDINGS: Research pertaining to the visual system in
      multiple sclerosis has identified new biomarkers of disease and is contributing
      to a better understanding of disease mechanisms. Progress has been made in the
      symptomatic management of visual manifestations of multiple sclerosis and visual
      outcome measures are now being included in clinical trials, with important
      quality of life ramifications. Perhaps the most prominent contribution from neuro
      ophthalmology research in multiple sclerosis has been the establishment of the
      visual system as a model to study disease pathogenesis, and for the systematic,
      objective, and longitudinal detection and monitoring of protective and
      restorative neurotherapeutic strategies. The emergence of these sophisticated
      capabilities has been in large part due to the application of high speed, high
      definition, and objective methods for the elucidation of both the structure and
      function of visual system networks. SUMMARY: Advances in neuro-ophthalmology
      research in multiple sclerosis have led to the establishment of the visual system
      as a model to objectively study disease pathogenesis, and for the identification
      of novel neurotherapeutic capabilities. With the prospects of myelin repair and
      neuroprotective agents increasingly becoming recognized as achievable goals, the
      validation and utility of new visual outcome measures quantifying changes in
      axonal integrity, myelin protection, and repair will likely prove invaluable.

PMID- 24751960
TI  - What is new about epidemiology of acute infectious encephalitis?
AB  - PURPOSE OF REVIEW: This review aims to describe new features on the epidemiology
      of encephalitis world-wide. As this neurological presentation is most frequently
      related to transmitted viruses, surveillance of encephalitis is of major
      importance to detect their emergence or re-emergence. RECENT FINDINGS: Rabies
      causes one of the most severe types of encephalitis as it is lethal in all cases,
      and it is endemic in some countries. It was thought that the virus had been
      eradicated in Western Europe, but it re-emerged in Greece and Italy. Physicians
      should be aware of this diagnosis in the case of severe encephalitis. Some
      viruses (Powassan, Nipah, and Hendra) are becoming endemic in some new parts of
      the world (USA and Australia). Because of their severity, they are healthcare
      concerns in those countries and for travelers (e.g. in Asia). Finally, a concept
      is emerging: herpes simplex virus is suspected to be a trigger for autoimmune
      encephalitis. This is of major importance for the future management of patients
      (corticosteroids early in the course of the disease?), and the epidemiology of
      sequelae. SUMMARY: Encephalitis is a good marker for the detection of emerging
      infections. New findings about the relationship between herpes simplex virus
      encephalitis and autoimmune encephalitis open a new concept for a better
      management of patients.

PMID- 24751961
TI  - Migraine and structural abnormalities in the brain.
AB  - PURPOSE OF REVIEW: The aim is to provide an overview of recent studies of
      structural brain abnormalities in migraine and to discuss the potential clinical
      significance of their findings. RECENT FINDINGS: Brain structure continues to be
      a topic of extensive research in migraine. Despite advances in neuroimaging
      techniques, it is not yet clear if migraine is associated with grey matter
      changes. Recent large population-based studies sustain the notion of increased
      prevalence of white matter abnormalities in migraine, and possibly of silent
      infarct-like lesions. The clinical relevance of this association is not clear.
      Structural changes are not related to cognitive decline, but a link to an
      increased risk of stroke, especially in patients with aura, cannot be ruled out.
      SUMMARY: Migraine may be a risk factor for structural changes in the brain. It is
      not yet clear how factors such as migraine sub-type, attack frequency, and sex
      affects this association. Additional longitudinal studies are needed to address
      these issues. Brain structure changes in migraine could potentially serve as
      disease biomarkers or as a mean of identifying sub-groups of patients with
      specific therapeutic needs and prognoses.

PMID- 24751962
TI  - The new therapeutic landscape in multiple sclerosis: exciting times and new
      perspectives.

PMID- 24751963
TI  - Prenatal stress and inhibitory neuron systems: implications for neuropsychiatric
      disorders.
AB  - Prenatal stress is a risk factor for several psychiatric disorders in which
      inhibitory neuron pathology is implicated. A growing body of research
      demonstrates that inhibitory circuitry in the brain is directly and persistently
      affected by prenatal stress. This review synthesizes research that explores how
      this early developmental risk factor impacts inhibitory neurons and how these
      findings intersect with research on risk factors and inhibitory neuron
      pathophysiology in schizophrenia, anxiety, autism and Tourette syndrome. The
      specific impact of prenatal stress on inhibitory neurons, particularly
      developmental mechanisms, may elucidate further the pathophysiology of these
      disorders. 

PMID- 24751966
TI  - Residents'corner April 2014. Nail it!: eye-catching nail folds.

PMID- 24751967
TI  - Exploring the boundary between a siphon and barometer in a hypobaric chamber.
AB  - Siphons have been used since ancient times, but exactly how they work is still a
      matter of debate. In order to elucidate the modus operandi of a siphon, a 1.5 m
      high siphon was set up in a hypobaric chamber to explore siphon behaviour in a
      low-pressure environment. When the pressure in the chamber was reduced to about
      0.18 atmospheres, a curious waterfall-like feature appeared downstream from the
      apex of the siphon. A hypothesis is presented to explain the waterfall
      phenomenon. When the pressure was reduced further the siphon broke into two
      columns--in effect becoming two back-to-back barometers. This experiment
      demonstrates the role of atmospheric pressure in explaining the hydrostatic
      characteristics of a siphon and the role of molecular cohesion in explaining the
      hydrodynamic aspects.

PMID- 24751965
TI  - Contributions of the social environment to first-onset and recurrent mania.
AB  - In treated cohorts, individuals with bipolar disorder are more likely to report
      childhood adversities and recent stressors than individuals without bipolar
      disorder; similarly, in registry-based studies, childhood adversities are more
      common among individuals who later become hospitalized for bipolar disorder.
      Because these types of studies rely on treatment-seeking samples or hospital
      diagnoses, they leave unresolved the question of whether or not social
      experiences are involved in the etiology of bipolar disorder. We investigated the
      role of childhood adversities and adulthood stressors in liability for bipolar
      disorder using data from the National Epidemiologic Survey on Alcohol and Related
      Conditions (n=33 375). We analyzed risk for initial-onset and recurrent DSM-IV
      (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition) manic
      episodes during the study's 3-year follow-up period. Childhood physical abuse and
      sexual maltreatment were associated with significantly higher risks of both first
      onset mania (odds ratio (OR) for abuse: 2.23; 95% confidence interval (CI)=1.71,
      2.91; OR for maltreatment: 2.10; CI=1.55, 2.83) and recurrent mania (OR for
      abuse: 1.55; CI=1.00, 2.40; OR for maltreatment: 1.60; CI=1.00, 2.55). In
      addition, past-year stressors in the domains of interpersonal instability and
      financial hardship were associated with a significantly higher risk of incident
      and recurrent mania. Exposure to childhood adversity potentiated the effects of
      recent stressors on adult mania. Our findings demonstrate a role of social
      experiences in the initial onset of bipolar disorder, as well as in its
      prospective course, and are consistent with etiologic models of bipolar disorder
      that implicate deficits in developmentally established stress-response pathways. 

PMID- 24751964
TI  - The P7C3 class of neuroprotective compounds exerts antidepressant efficacy in
      mice by increasing hippocampal neurogenesis.
AB  - Augmenting hippocampal neurogenesis represents a potential new strategy for
      treating depression. Here we test this possibility by comparing hippocampal
      neurogenesis in depression-prone ghrelin receptor (Ghsr)-null mice to that in
      wild-type littermates and by determining the antidepressant efficacy of the P7C3
      class of neuroprotective compounds. Exposure of Ghsr-null mice to chronic social
      defeat stress (CSDS) elicits more severe depressive-like behavior than in CSDS
      exposed wild-type littermates, and exposure of Ghsr-null mice to 60% caloric
      restriction fails to elicit antidepressant-like behavior. CSDS resulted in more
      severely reduced cell proliferation and survival in the ventral dentate gyrus
      (DG) subgranular zone of Ghsr-null mice than in that of wild-type littermates.
      Also, caloric restriction increased apoptosis of DG subgranular zone cells in
      Ghsr-null mice, although it had the opposite effect in wild-type littermates.
      Systemic treatment with P7C3 during CSDS increased survival of proliferating DG
      cells, which ultimately developed into mature (NeuN+) neurons. Notably, P7C3
      exerted a potent antidepressant-like effect in Ghsr-null mice exposed to either
      CSDS or caloric restriction, while the more highly active analog P7C3-A20 also
      exerted an antidepressant-like effect in wild-type littermates. Focal ablation of
      hippocampal stem cells with radiation eliminated this antidepressant effect,
      further attributing the P7C3 class antidepressant effect to its neuroprotective
      properties and resultant augmentation of hippocampal neurogenesis. Finally, P7C3
      A20 demonstrated greater proneurogenic efficacy than a wide spectrum of currently
      marketed antidepressant drugs. Taken together, our data confirm the role of
      aberrant hippocampal neurogenesis in the etiology of depression and suggest that
      the neuroprotective P7C3-compounds represent a novel strategy for treating
      patients with this disease. 

PMID- 24751968
TI  - Differential anti-diabetic effects and mechanism of action of charantin-rich
      extract of Taiwanese Momordica charantia between type 1 and type 2 diabetic mice.
AB  - Momordica charantia Linn. (Cucurbitaceae), also called bitter melon, has
      traditionally been used as a natural anti-diabetic agent for anti-hyperglycemic
      activity in several animal models and clinical trials. We investigated the
      differences in the anti-diabetic properties and mechanism of action of Taiwanese
      M. charantia (MC) between type 1 diabetic (T1D) and type 2 diabetic (T2D) mice.
      To clarify the beneficial effects of MC, we measured non-fasting glucose, oral
      glucose tolerance, and plasma insulin levels in KK/HIJ mice with high-fat diet
      induced diabetes (200 mg/kg/day of charantin-rich extract of MC [CEMC]) and in
      ICR mice with STZ-induced diabetes. After 8 weeks, all the mice were
      exsanguinated, and the expression of the insulin-signaling-associated proteins in
      their tissue was evaluated, in coordination with the protective effects of CEMC
      against pancreatic beta-cell toxicity (in vitro). Eight weeks of data indicated
      that CEMC caused a significant decline in non-fasting blood glucose, plasma
      glucose intolerance, and insulin resistance in the KK/HIJ mice, but not in the
      ICR mice. Furthermore, CEMC decreased plasma insulin and promoted the sensitivity
      of insulin by increasing the expression of GLUT4 in the skeletal muscle and of
      IRS-1 in the liver of KK/HIJ mice; however, CEMC extract had no effect on the
      insulin sensitivity of ICR mice. In vitro study showed that CEMC prevented
      pancreatic beta cells from high-glucose-induced cytotoxicity after 24 h of
      incubation, but the protective effect was not detectable after 72 h.
      Collectively, the hypoglycemic effects of CEMC suggest that it has potential for
      increasing insulin sensitivity in patients with T2D rather than for protecting
      patients with T1D against beta-cell dysfunction.

PMID- 24751969
TI  - Protective effect of curcumin against heavy metals-induced liver damage.
AB  - Occupational or environmental exposures to heavy metals produce several adverse
      health effects. The common mechanism determining their toxicity and
      carcinogenicity is the generation of oxidative stress that leads to hepatic
      damage. In addition, oxidative stress induced by metal exposure leads to the
      activation of the nuclear factor (erythroid-derived 2)-like 2/Kelch-like ECH
      associated protein 1/antioxidant response elements (Nrf2/Keap1/ARE) pathway.
      Since antioxidant and chelating agents are generally used for the treatment of
      heavy metals poisoning, this review is focused on the protective role of curcumin
      against liver injury induced by heavy metals. Curcumin has shown, in clinical and
      preclinical studies, numerous biological activities including therapeutic
      efficacy against various human diseases and anti-hepatotoxic effects against
      environmental or occupational toxins. Curcumin reduces the hepatotoxicity induced
      by arsenic, cadmium, chromium, copper, lead and mercury, prevents histological
      injury, lipid peroxidation and glutathione (GSH) depletion, maintains the liver
      antioxidant enzyme status and protects against mitochondrial dysfunction. The
      preventive effect of curcumin on the noxious effects induced by heavy metals has
      been attributed to its scavenging and chelating properties, and/or to the ability
      to induce the Nrf2/Keap1/ARE pathway. However, additional research is needed in
      order to propose curcumin as a potential protective agent against liver damage
      induced by heavy metals. 

PMID- 24751970
TI  - Antrodia cinnamomea profoundly exalted the reversion of activated hepatic
      stellate cells by the alteration of cellular proteins.
AB  - The direct modulation of Antrodia cinnamomea (AC) on the prominent role of liver
      fibrosis-hepatic stellate cells (HSCs) in situ remains unclear. Firstly, the
      administration of A. cinnamomea mycelial extract (ACME) could improve liver
      morphology and histological changes including collagen formation and GPT activity
      in the liver of thioacetamide (TAA)-injured rats. The morphology and fatty acid
      restore of TAA-induced HSCs (THSCs) returned to the non-chemical induced HSCs
      (NHSCs) type as measured by immunofluorescence and Oil Red O staining. PPARgamma
      was upregulated associated with the lowering of alpha-SMA protein in NHSC-ACME.
      ACME inhibited the MMP-2 activity in NHSCs by gelatin Zymography. After LC-MS/MS,
      the cytoskeleton (tubulin, lamin A) and heat shock protein 8 in NHSC-ACME, and
      guanylate kinase, brain-specific kinase, SG-II and p55 proteins were
      downregulated in THSC-ACME. Whereas MHC class II, SMC6 protein, and phospholipase
      D were upregulated in NHSC-ACME. Furthermore, PKG-1 was downregulated in NHSC
      ACME and upregulated in THSC-ACME. SG-II and p55 proteins were downregulated in
      NHSC-ACME and THSC-ACME by Western blotting. Taken together, the beneficial
      effect of A. cinnamomea on the induction of HSC cellular proteins is potentially
      applied as an alternative and complementary medicine for the prevention and
      amelioration of a liver injury. 

PMID- 24751971
TI  - The potential effect of berberine in mercury-induced hepatorenal toxicity in
      albino rats.
AB  - Mercury (Hg) is the third most dangerous heavy metal after arsenic and lead.
      Mercury's toxicity brings serious risks to health through negative pathological
      and biochemical effects. The study was designed to investigate the possible
      protective role of berberine (BN) in mercuric chloride (HgCl2) induced oxidative
      stress in hepatic and renal tissues. Adult male albino Wistar rats were exposed
      to mercuric chloride (HgCl2; 0.4 mg/kg bwt) for 7 days. Treatment with HgCl2
      induced oxidative stress by increasing lipid peroxidation and nitric oxide
      production along with a concomitant decrease in glutathione and various
      antioxidant enzymes, namely superoxide dismutase, catalase, glutathione
      peroxidase and glutathione reductase. HgCl2 intoxication increased the activities
      of liver enzymes and the bilirubin level, in addition to the levels of urea and
      creatinine in serum. BN (100mg/kg bwt) treatment inhibited lipid peroxidation and
      nitric oxide production, whereas it increased glutathione content. Activities of
      antioxidants enzymes, superoxide dismutase, catalase, glutathione peroxidase and
      glutathione reductase, were also restored concomitantly when compared to control
      after BN administration. BN also inhibited the apoptotic effect of HgCl2 by
      increasing the expression of Bcl-2 protein in liver and kidney. Histopathological
      examination of the liver and kidney tissues proved the protective effect of BN
      against HgCl2 toxicity. These results demonstrated that BN augments antioxidant
      defense against HgCl2-induced toxicity and provides evidence that it has
      therapeutic potential as hepato- and reno-protective agent.

PMID- 24751972
TI  - Evaluations of the mutagenicity of a pigment extract from bulb culture of
      Hippeastrum reticulatum.
AB  - The use of anthocyanins in food products as colorants has been limited because of
      their instability toward alkaline pH and high temperature. This study aimed to
      determine color stability and mutagenicity of the anthocyanin-based pigment
      extract from bulb cultures of Hippeastrum (Hippeastrum reticulatum). The pigment
      extract retained its reddish-orange color under alkaline conditions (?pH 11) and
      was stable up to 6 h at 95  degrees C. The mutagenicity of the extract was
      evaluated in vitro and in vivo. Hippeastrum pigment extract up to 1.25 mg plate(
      1) was found non-mutagenic in Ames test using Salmonella typhimurium strain TA98
      and TA100. Chromosome aberrations were observed when human lymphocytes were
      treated with the extract up to 1.5 mg ml(-1). However, the extract up to 1.4 mg
      ml(-1) was found to exhibit relatively low or no mutagenicity in in vitro comet
      assays with human lymphocytes. In in vivo micronucleated reticulocyte assay, mice
      were treated orally with the extract up to 1 g kg(-1). No significant increase of
      the percentage of micronucleated peripheral reticulocytes compared to the
      negative control groups was found. Taken together, our study indicates that
      Hippeastrum pigment extract is potentially applicable as an additive colorant in
      the diet and related products.

PMID- 24751973
TI  - Polysaccharide extract of Cordyceps sobolifera attenuates renal injury in
      endotoxemic rats.
AB  - Extracts derived from Cordyceps have been demonstrated to possess various
      pharmacological effects, including immunomodulatory, antitumor, hypoglycemic, and
      antioxidant activities. This study was aimed to clarify the role of CS-P, a
      polysaccharide fraction isolated from Cordyceps sobolifera, in modulating
      nephrofunctional damage in a rat model of endotoxemia. CS-P (500 mg/kg body
      weight) was orally administered to rats for 4 weeks before the peritoneal
      injection of lipopolysaccharide (LPS, 10 mg/kg body weight). Pre-treatment with
      CS-P significantly attenuated the deleterious renal functions caused by LPS,
      i.e., elevated blood urea nitrogen and creatinine as well as urine protein.
      Histopathological examination of kidney tissues also demonstrated that CS-P
      improved LPS-induced pathological abnormalities. The induction of inducible
      nitric oxide synthase and the overproduction of nitric acid by LPS were also
      significantly reduced by CS-P via inhibiting nuclear factor-kappaB activation. In
      addition, CS-P pre-treatment suppressed the plasma levels of tumor necrosis
      factor-alpha and interleukin-6. Concurrently, CS-P supplementation potently
      suppressed the LPS-induced rise of lipid peroxidation and markedly enhanced the
      antioxidant defense system by restoring the levels of superoxide dismutase,
      glutathione peroxidase, and catalase in kidney. The present results suggested
      that CS-P pre-treatment could protect against LPS-triggered inflammatory
      responses and renal injury in rats.

PMID- 24751974
TI  - DHA2, a synthesized derivative of bisbibenzyl, exerts antitumor activity against
      ovarian cancer through inhibition of XIAP and Akt/mTOR pathway.
AB  - The analysis of dihydroptychantol (DHA) and its chemically synthesized
      macrocyclic bisbibenzyl derivatives (DHA1, 2 and 3) led to the selection of DHA2
      as a potential drug candidate for ovarian cancer. The exposure of ovarian cancer
      SKOV3 cells to DHA2 resulted in the downregulation of the anti-apoptotic X-linked
      inhibitor of apoptosis protein (XIAP) and Bcl-2 and led to caspase-independent
      cell death. The overexpression of XIAP reversed DHA2-induced cell death, and the
      depletion of XIAP had the opposite effect. DHA2 could induce autophagy, as
      evidenced by increases in the formation of acidic vesicular organelles and the
      processing of LC3B-I to LC3B-II. Pretreatment with autophagy inhibitors
      potentiated DHA2-mediated cell death. We showed that typical PI3K/Akt signaling
      was involved in DHA2-mediated cell death. The overexpression of Akt almost
      completely reversed DHA2-induced cell death, and the inactivation of Akt
      significantly facilitated DHA2-induced cell death. The administration of DHA2 to
      xenograft mice reduced tumor growth by causing Akt inactivation, the conversion
      of LC3B and proliferation inhibition. Our study demonstrates that the inhibition
      of XIAP and the inactivation of Akt/mTOR facilitate the efficacy of DHA2 in
      ovarian cancer cells. 

PMID- 24751975
TI  - Implementing a resident research program to overcome barriers to resident
      research.
AB  - Internal medicine residents are required to participate in scholarly activity,
      but conducting original research during residency is challenging. Following a
      poor Match at Baystate Medical Center, the authors implemented a resident
      research program to overcome known barriers to resident research. The
      multifaceted program addressed the following barriers: lack of interest, lack of
      time, insufficient technical support, and paucity of mentors. The program
      consisted of evidence-based medicine training to stimulate residents' interest in
      research and structural changes to support their conduct of research, including
      protected time for research during ambulatory blocks, a research assistant to
      help with tasks such as institutional review board applications and data entry, a
      research nurse to help with data collection, easily accessible biostatistical
      support, and a resident research director to provide mentorship. Following
      implementation in the fall of 2005, there was a steady rise in the number of
      resident presentations at national meetings, then in the number of resident
      publications. From 2001 to 2006, the department saw 3 resident publications. From
      2006 to 2012, that number increased to 39 (P< .001). The department also saw more
      original research (29 publications) and resident first authors (12 publications)
      after program implementation. The percentage of residents accepted into
      fellowships rose from 33% before program implementation to 49% after (P = .04).
      This comprehensive resident research program, which focused on evidence-based
      medicine and was tailored to overcome specific barriers, led to a significant
      increase in the number of resident Medline publications and improved the
      reputation of the residency program. 

PMID- 24751976
TI  - "Making strange": a role for the humanities in medical education.
AB  - Stories, film, drama, and art have been used in medical education to enhance
      empathy, perspective-taking, and openness to "otherness," and to stimulate
      reflection on self, others, and the world. Yet another, equally important
      function of the humanities and arts in the education of physicians is that of
      "making strange"-that is, portraying daily events, habits, practices, and people
      through literature and the arts in a way that disturbs and disrupts one's
      assumptions, perspectives, and ways of acting so that one sees the self, others,
      and the world anew. Tracing the development of this concept from Viktor
      Shklovsky's "enstrangement" (ostranenie) through Bertolt Brecht's "alienation
      effect," this essay describes the use of this technique to disrupt the
      "automaticity of thinking" in order to discover new ways of perceiving and being
      in the world.Enstrangement may be used in medical education in order to stimulate
      critical reflection and dialogue on assumptions, biases, and taken-for-granted
      societal conditions that may hinder the realization of a truly humanistic
      clinical practice. In addition to its ability to enhance one's critical
      understanding of medicine, the technique of "making strange" does something else:
      By disrupting fixed beliefs, this approach may allow a reexamination of patient
      physician relationships in terms of human interactions and provide health care
      professionals an opportunity-an "open space"-to bear witness and engage with
      other individuals during challenging times. 

PMID- 24751977
TI  - Characterization of the inflammatory infiltrate in Streptococcus pneumoniae
      pneumonia in young and elderly patients.
AB  - There is an increased susceptibility and mortality in the elderly due to
      pneumonia caused by Streptococcus pneumoniae. We aimed to assess the inflammatory
      cell composition with respect to age in pneumococcal pneumonia patients.
      Neutrophilic granulocytes and various lymphocyte and macrophage subpopulations
      were immunohistochemically quantified on lung tissue specimens of young (n = 5;
      mean age 8.4 years), middle-aged (n = 8; mean age 55.9 years) and elderly (n = 9;
      mean age 86.6 years) pneumonia patients with microbiologically proven S.
      pneumoniae pneumonia. We discovered a higher percentage of neutrophilic
      granulocytes in elderly as opposed to young patients (95 vs. 75%, p = 0.012).
      Conversely, young patients versus elderly patients had more alveolar macrophages
      (CD11c+: 20 vs. 9%, p = 0.029) and M1 macrophages (CD14+: 30 vs. 10%, p = 0.012
      and HLA-DR+: 52 vs. 11%, p = 0.019). There was no significant difference
      concerning M2 macrophages and lymphocytes. Comparison of young patients with
      middle-aged patients showed similar significant results for alveolar macrophages
      (p = 0.019) and subsignificant results for M1 macrophages and neutrophilic
      granulocytes (p < 0.08). This is the first study characterizing the inflammatory
      infiltrate of pneumococcal pneumonia in situ. Our observations improve the
      understanding of the innate immune mechanisms of pneumococcal lung infection and
      point at the potential of therapies for restoring macrophage function and
      decreasing neutrophilic influx in order to help prevent or cure pneumonia.

PMID- 24751978
TI  - Birth of healthy offspring following ICSI in in vitro-matured common marmoset
      (Callithrix jacchus) oocytes.
AB  - Intracytoplasmic sperm injection (ICSI), an important method used to treat male
      subfertility, is applied in the transgenic technology of sperm-mediated gene
      transfer. However, no study has described successful generation of offspring
      using ICSI in the common marmoset, a small non-human primate used as a model for
      biomedical translational research. In this study, we investigated blastocyst
      development and the subsequent live offspring stages of marmoset oocytes matured
      in vitro and fertilized by ICSI. To investigate the optimal timing of performing
      ICSI, corrected immature oocytes were matured in vitro and ICSI was performed at
      various time points (1-2 h, 2-4 h, 4-6 h, 6-8 h, and 8-10 h after extrusion of
      the first polar body (PB)). Matured oocytes were then divided randomly into two
      groups: one was used for in vitro fertilization (IVF) and the other for ICSI. To
      investigate in vivo development of embryos followed by ICSI, 6-cell- to 8-cell
      stage embryos and blastocysts were nonsurgically transferred into recipient
      marmosets. Although no significant differences were observed in the fertilization
      rate of blastocysts among ICSI timing after the first PB extrusion, the
      blastocyst rate at 1-2 h was lowest among groups at 2-4 h, 4-6 h, 6-8 h, and 8-10
      h. Comparing ICSI to IVF, the fertilization rates obtained in ICSI were higher
      than in IVF (p>0.05). No significant difference was noted in the cleaved
      blastocyst rate between ICSI and IVF. Following the transfer of 37 ICSI
      blastocysts, 4 of 20 recipients became pregnant, while with the transfer of 21 6
      cell- to 8-cell-stage ICSI embryos, 3 of 8 recipients became pregnant. Four
      healthy offspring were produced and grew normally. These are the first marmoset
      offspring produced by ICSI, making it an effective fertilization method for
      marmosets. 

PMID- 24751980
TI  - Secreted clusterin gene silencing enhances chemosensitivity of a549 cells to
      cisplatin through AKT and ERK1/2 pathways in vitro.
AB  - BACKGROUND/AIMS: Several studies have shown secreted clusterin (sCLU) silencing
      directed against sCLU mRNA in sCLU-rich lung cancer cell lines sensitized cells
      to chemotherapy. However, the molecular mechanisms underlying the effect of sCLU
      silencing on lung cancer cell chemosensitivity is not known. In the present
      study, we aimed to determine that vector expressing short hairpin RNA against
      sCLU RNA (sCLU-shRNA) enhances the chemosensitivity in human small cell lung
      cancer A549 cells in vitro by inhibition of phosphorylated ERK1/2 (p-ERK1/2) and
      Akt (p-Akt). METHODS: The pCDNA3.1-sCLU and control scrambled pCDNA3.1 plasmid
      was constructed. We investigated the effects of sCLU overexpression by pCDNA3.1
      sCLU transfection on chemosensitivity to cisplatin (DDP) in A549 cells in vitro.
      We down-regulated sCLU expression by short hairpin RNA against sCLU RNA (sCLU
      shRNA) and investigated the effects on chemosensitivity to DDP in A549 cells and
      A549(DDP)in vitro. In order to confirm the correlation between sCLU and AKT and
      ERK1/2 signals, cells were treated with wortmannin and U0126. RESULTS: We found
      the chemotherapeutic agent DDP activated sCLU. Overexpression of sCLU increased
      cellular DDP chemoresistance in the A549(DDP) and pCDNA3. 1-sCLU transfected A549
      cells via inhibition DDP-induced apoptosis. Whereas sCLU knockdown induced
      chemosensitization in the S549 and A549(DDP) cells via increase of DDP-induced
      apoptosis. sCLU overexpression activated pAKT Ser(473) and
      pERK1/2(Thr202/Tyr204), and vice versa. Inhibition of pAKT Ser(473) and
      pERK1/2(Thr202/Tyr204) was sufficient to induce significant recover y in
      chemosensitivity to DDP in A549(DDP) in the presence of sCLU overexpression. The
      DDP activated sCLU, which directly regulated pAKT and pERK1/2. CONCLUSIONS: This
      novel finding suggests that therapies directed against sCLU and its downstream
      signaling targets pAKT and pERK1/2 may have the potential to enhance the efficacy
      of DDP-based chemotherapy.

PMID- 24751979
TI  - The molecular evolution of cytochrome P450 genes within and between drosophila
      species.
AB  - We map 114 gene gains and 74 gene losses in the P450 gene family across the
      phylogeny of 12 Drosophila species by examining the congruence of gene trees and
      species trees. Although the number of P450 genes varies from 74 to 94 in the
      species examined, we infer that there were at least 77 P450 genes in the
      ancestral Drosophila genome. One of the most striking observations in the data
      set is the elevated loss of P450 genes in the Drosophila sechellia lineage. The
      gain and loss events are not evenly distributed among the P450 genes-with 30
      genes showing no gene gains or losses whereas others show as many as 20 copy
      number changes among the species examined. The P450 gene clades showing the
      fewest number of gene gain and loss events tend to be those evolving with the
      most purifying selection acting on the protein sequences, although there are
      exceptions, such as the rapid rate of amino acid replacement observed in the
      single copy phantom (Cyp306a1) gene. Within D. melanogaster, we observe gene copy
      number polymorphism in ten P450 genes including multiple cases of interparalog
      chimeras. Nonallelic homologous recombination (NAHR) has been associated with
      deleterious mutations in humans, but here we provide a second possible example of
      an NAHR event in insect P450s being adaptive. Specifically, we find that a
      polymorphic Cyp12a4/Cyp12a5 chimera correlates with resistance to an insecticide.
      Although we observe such interparalog exchange in our within-species data sets,
      we have little evidence of it between species, raising the possibility that such
      events may occur more frequently than appreciated but are masked by subsequent
      sequence change. 

PMID- 24751981
TI  - Evaluation of the CENTURY model using long-term fertilization trials under corn
      wheat cropping systems in the typical croplands of China.
AB  - Soil organic matter models are widely used to study soil organic carbon (SOC)
      dynamics. Here, we used the CENTURY model to simulate SOC in wheat-corn cropping
      systems at three long-term fertilization trials. Our study indicates that CENTURY
      can simulate fertilization effects on SOC dynamics under different climate and
      soil conditions. The normalized root mean square error is less than 15% for all
      the treatments. Soil carbon presents various changes under different
      fertilization management. Treatment with straw return would enhance SOC to a
      relatively stable level whereas chemical fertilization affects SOC differently
      across the three sites. After running CENTURY over the period of 1990-2050, the
      SOC levels are predicted to increase from 31.8 to 52.1 Mg ha-1 across the three
      sites. We estimate that the carbon sequestration potential between 1990 and 2050
      would be 9.4-35.7 Mg ha-1 under the current high manure application at the three
      sites. Analysis of SOC in each carbon pool indicates that long-term fertilization
      enhances the slow pool proportion but decreases the passive pool proportion.
      Model results suggest that change in the slow carbon pool is the major driver of
      the overall trends in SOC stocks under long-term fertilization. 

PMID- 24751982
TI  - Self-medication of psoriasis in southwestern China.
AB  - BACKGROUND: Medication adherence is essential for psoriasis management. Although
      studies have determined the prevalence and correlative factors of non-adherence,
      as far as we know, there has been no study specifically addressing them in China.
      METHODS: Anonymous 23-item questionnaires were distributed to 324 psoriatic
      patients from June 2012 to June 2013. chi(2) test, normality test, Student's t
      test or Mann-Whitney U test, Bonferroni correction and the binary logistic
      regression model were applied. RESULTS: Self-medication of psoriasis was high in
      China (82.4%). Joint involvement, absence of communication with families and
      short communication duration with doctors were the three top factors affecting
      adherence. Besides low efficacy (16.0%) and recurrence frustration (27.0%), we
      found that patients' deception by sham advertisings (24.1%) is an non-negligible
      issue. CONCLUSION: Psoriasis self-medication in China was high. Improvement of
      patients' communication with families and/or doctors were suggested to be crucial
      to enhance adherence. Meanwhile, extermination of sham advertisings by
      administrative agencies is of great concern.

PMID- 24751983
TI  - Effect of age at exposure in 11 underground miners studies.
AB  - Eleven underground miners studies evaluated the risk of lung cancer from exposure
      in underground mines. Nearly 68,000 miners were included in the joint study,
      contributing to nearly 2700 lung cancers. The resulting model of the Biological
      Effects of Ionizing Radiation (BEIR) VI Committee considered linear exposure
      response relationship, which was modified by time since exposure (TE), attained
      age and exposure rate. The effect of age at exposure (AE) was not explicitly
      evaluated. The presentation aims to show that the modifying effect of AE is
      substantial if time-since-exposure modification is simultaneously used in the
      model. When the excess relative risk per unit exposure (ERR/WLM) is adjusted for
      TE, the ERR/WLM corresponding to AE<15 is 0.013 and in subsequent categories
      decreased gradually up to the AE of 40 and more years, which was only 0.004. In
      comparison with the BEIR VI model, the present model predicts higher risks at
      younger ages and the risk decreases more rapidly.

PMID- 24751984
TI  - In vivo dose evaluation during gynaecological radiotherapy using L-alanine/ESR
      dosimetry.
AB  - The dose delivered by in vivo 3-D external beam radiation therapy (EBRT) was
      verified with L-alanine/electron spin resonance (ESR) dosimetry for patients
      diagnosed with gynaecological cancer. Measurements were performed with an X-band
      ESR spectrometer. Dosemeters were positioned inside the vaginal cavity with the
      assistance of an apparatus specially designed for this study. Previous phantom
      studies were performed using the same conditions as in the in vivo treatment.
      Four patients participated in this study during 20-irradiation sessions, giving
      220 dosemeters to be analysed. The doses were determined with the treatment
      planning system, providing dose confirmation. The phantom study resulted in a
      deviation between -2.5 and 2.1 %, and for the in vivo study a deviation between 
      9.2 and 14.2 % was observed. In all cases, the use of alanine with ESR was
      effective for dose assessment, yielding results consistent with the values set
      forth in the International Commission on Radiation Units and Measurements (ICRU)
      reports.

PMID- 24751985
TI  - Lung cancer risk due to residential radon exposures: estimation and prevention.
AB  - Epidemiological studies proved that cumulative exposure to radon is the second
      leading cause of lung cancer, the world's most common cancer. The objectives of
      the present study are (i) to analyse lung cancer risk for chronic, low radon
      exposures based on the transformation frequency-tissue response (TF-TR) model
      formulated in terms of alpha particle hits in cell nuclei; (ii) to assess the
      percentage of attributable lung cancers in six areas of Transylvania where the
      radon concentration was measured and (iii) to point out the most efficient
      remediation measures tested on a pilot house in Stei, Romania. Simulations
      performed with the TF-TR model exhibit a linear dose-effect relationship for
      chronic, residential radon exposures. The fraction of lung cancer cases
      attributed to radon ranged from 9 to 28% for the investigated areas. Model
      predictions may represent a useful tool to complement epidemiological studies on
      lung cancer risk and to establish reasonable radiation protection regulations for
      human safety.

PMID- 24751987
TI  - Do not forget that type 2 diabetes does not only expose to cardiovascular
      complications.

PMID- 24751986
TI  - Independent adipogenic and contractile properties of fibroblasts in Graves'
      orbitopathy: an in vitro model for the evaluation of treatments.
AB  - Graves' orbitopathy (GO) is a disfiguring and sometimes blinding disease,
      characterised by inflammation and swelling of orbital tissues, with fibrosis and
      adipogenesis being predominant features. Little is known about the disease
      aetiology and the molecular mechanisms driving the phenotypic changes in orbital
      fibroblasts are unknown. Using fibroblasts isolated from the orbital fat of
      undiseased individuals or GO patients, we have established a novel in vitro model
      to evaluate the dual profile of GO cells in a three-dimensional collagen matrix;
      this pseudo-physiological 3D environment allows measurement of their contractile
      and adipogenic properties. GO cells contracted collagen matrices more efficiently
      than control cells following serum or TGFbeta1 stimulation, and showed a slightly
      increased ability to proliferate in the 3D matrix, in accordance with a fibro
      proliferative phenotype. GO cells, unlike controls, also spontaneously
      differentiated into adipocytes in 3D cultures - confirming an intrinsic
      adipogenic profile. However, both control and GO cells underwent adipogenesis
      when cultured under pathological pressure levels. We further demonstrate that a
      Thy-1-low population of GO cells underlies the adipogenic - but not the
      contractile - phenotype and, using inhibitors, confirm that the contractile and
      adipogenic phenotypes are regulated by separate pathways. In view of the current
      lack of suitable treatment for GO, we propose that this new model testing the
      duality of the GO phenotype could be useful as a preclinical evaluation for the
      efficacy of potential treatments. 

PMID- 24751989
TI  - Polymerase chain reaction-denaturing gradient gel electrophoresis (PCR-DGGE): a
      promising tool to diagnose bacterial infections in diabetic foot ulcers.
AB  - AIM: The diagnosis of diabetic foot infections is difficult due to limitations of
      conventional culture-based techniques. The objective of this study was to
      evaluate the contribution of denaturing gradient gel electrophoresis (DGGE) in
      the microbiological diagnosis of diabetic foot ulcers in comparison to
      conventional techniques, and also to evaluate the need to perform a biopsy sample
      for this diagnosis. METHODS: Twenty diabetic patients (types 1 and 2) with foot
      ulcers (grades 1-4) were included. After debridement of their wounds, samples
      were taken in duplicate by surface swabbing and deep-tissue biopsy. The samples
      were analyzed by conventional culture and by a new molecular biology tool, DGGE
      technology. RESULTS: Polymerase chain reaction (PCR)-DGGE led to the
      identification of more bacteria than did conventional cultures (mean: 2.35 vs
      0.80, respectively). In 11 cases, the technology detected pathogenic species not
      isolated by classical cultures. PCR-DGGE also identified significantly more
      pathogenic species at deep levels compared with species detected at superficial
      levels (87% vs 58%, respectively; P = 0.03). In 9/20 cases, pathogenic bacteria
      were detected only in deep samples, revealing the need to perform tissue biopsy
      sampling. CONCLUSION: DGGE, achievable in 48h, could be a useful technique for
      the bacteriological diagnosis of diabetic foot infections. It may help to
      identify pathogenic bacteria in deeply infected ulcers, thereby contributing to a
      more appropriate use of antibiotics.

PMID- 24751990
TI  - Infants detect changes in everyday scenes: the role of scene gist.
AB  - When watching physical events, infants bring to bear prior knowledge about
      objects and readily detect changes that contradict physical rules. Here we
      investigate the possibility that scene gist may affect infants, as it affects
      adults, when detecting changes in everyday scenes. In Experiment 1, 15-month-old
      infants missed a perceptually salient change that preserved the gist of a generic
      outdoor scene; the same change was readily detected if infants had insufficient
      time to process the display and had to rely on perceptual information for change
      detection. In Experiment 2, 15-month-olds detected a perceptually subtle change
      that preserved the scene gist but violated the rule of object continuity,
      suggesting that physical rules may overpower scene gist in infants' change
      detection. Finally, Experiments 3 and 4 provided converging evidence for the
      effects of scene gist, showing that 15-month-olds missed a perceptually salient
      change that preserved the gist and detected a perceptually subtle change that
      disrupted the gist. Together, these results suggest that prior knowledge,
      including scene knowledge and physical knowledge, affects the process by which
      infants maintain their representations of everyday scenes. 

PMID- 24751988
TI  - Ethnic differences in the relationship between birth weight and type 2 diabetes
      mellitus in postmenopausal women.
AB  - AIM: The objective of this study is to examine the relationship between self
      reported birth weight and the adult occurrence of type 2 diabetes mellitus in a
      large multi-ethnic population of women. METHODS: Baseline data from the Women's
      Health Initiative Observational Study [n=75,993] was used to examine the
      association between participant birth weight category and prevalent type 2
      diabetes mellitus. Models were adjusted for age, ethnicity, body mass index and
      other pertinent risk factors. Sub-analyses were performed stratifying by
      ethnicity. RESULTS: There was a strong inverse association between birth weight
      and type 2 diabetes mellitus with a birth weight of <6 pounds (lbs) (OR: 1.16,
      95% CI: 1.01, 1.33) significantly associated with an increased risk of type 2
      diabetes mellitus and a birth weight of >=10 lbs (OR: 0.72, 95% CI: 0.57, 0.92)
      associated with a decreased risk of type 2 diabetes mellitus compared to women
      who reported their birth weight between 7 and 8 lbs 15 ounces (oz). Stratifying
      by ethnicity, the inverse association between birth weight and type 2 diabetes
      mellitus was only apparent in White women, but not Black, Hispanic or Asian
      women. CONCLUSION: Lower birth weight was associated with increased T2D risk in
      American White and Black post-menopausal women.

PMID- 24751991
TI  - Electrophysiological evidence for automatic processing of erroneous stimuli.
AB  - In a paradigm combining color-word Stroop and misspelled words processing,
      spelling mistakes were placed in half the Stroop stimuli. Participants were
      presented with words written in different ink colors and asked to identify the
      color of the ink while ignoring the word meaning. Importantly, whether the word
      was correctly spelled or not was completely irrelevant to the task. The spelling
      manipulation did not change the phonology or semantic meaning of the words.
      Congruency and spelling correctness were manipulated orthogonally and interacted
      at the behavioral level. Event-related potentials showed a very early processing
      of misspelled words. The present findings are in line with the idea of anterior
      cingulate cortex (ACC) involvement in cognitive monitoring, expressed mainly in
      the theta frequency band. The present study demonstrates that this monitoring
      mechanism is elicited automatically, in other words, this mechanism perceives
      erroneous stimuli even when they are absolutely irrelevant to the participant's
      task. At later processing stages, the same central monitoring mechanism is also
      involved in the detection/resolution of conflict. 

PMID- 24751992
TI  - The nature of face representations in subcortical regions.
AB  - Studies examining the neural correlates of face perception in humans have focused
      almost exclusively on the distributed cortical network of face-selective regions.
      Recently, however, investigations have also identified subcortical correlates of
      face perception and the question addressed here concerns the nature of these
      subcortical face representations. To explore this issue, we presented to
      participants pairs of images sequentially to the same or to different eyes.
      Superior performance in the former over latter condition implicates monocular,
      prestriate portions of the visual system. Over a series of five experiments, we
      manipulated both lower-level (size, location) as well as higher-level (identity)
      similarity across the pair of faces. A monocular advantage was observed even when
      the faces in a pair differed in location and in size, implicating some
      subcortical invariance across lower-level image properties. A monocular advantage
      was also observed when the faces in a pair were two different images of the same
      individual, indicating the engagement of subcortical representations in more
      abstract, higher-level aspects of face processing. We conclude that subcortical
      structures of the visual system are involved, perhaps interactively, in multiple
      aspects of face perception, and not simply in deriving initial coarse
      representations. 

PMID- 24751993
TI  - Cortical pitch response components index stimulus onset/offset and dynamic
      features of pitch contours.
AB  - Voice pitch is an important information-bearing component of language that is
      subject to experience dependent plasticity at both early cortical and subcortical
      stages of processing. We have already demonstrated that pitch onset component
      (Na) of the cortical pitch response (CPR) is sensitive to flat pitch and its
      salience ... CPR responses from Chinese listeners were elicited by three citation
      forms varying in pitch acceleration and duration. Results showed that the pitch
      onset component (Na) was invariant to changes in acceleration. In contrast, Na-Pb
      and Pb-Nb showed a systematic decrease in the interpeak latency and decrease in
      amplitude with increase in pitch acceleration that followed the time course of
      pitch change across the three stimuli. A strong correlation with pitch
      acceleration was observed for these two components only - a putative index of
      pitch-relevant neural activity associated with the more rapidly-changing portions
      of the pitch contour. Pc-Nc marks unambiguously the stimulus offset ... and their
      functional roles as related to sensory and cognitive properties of the stimulus.
      [Corrected]

PMID- 24751994
TI  - Electrophysiological correlates of cross-linguistic semantic integration in
      hearing signers: N400 and LPC.
AB  - We explored semantic integration mechanisms in native and non-native hearing
      users of sign language and non-signing controls. Event-related brain potentials
      (ERPs) were recorded while participants performed a semantic decision task for
      priming lexeme pairs. Pairs were presented either within speech or across speech
      and sign language. Target-related ERP responses were subjected to principal
      component analyses (PCA), and neurocognitive basis of semantic integration
      processes were assessed by analyzing the N400 and the late positive complex (LPC)
      components in response to spoken (auditory) and signed (visual) antonymic and
      unrelated targets. Semantically-related effects triggered across modalities would
      indicate a similar tight interconnection between the signers' two languages like
      that described for spoken language bilinguals. Remarkable structural similarity
      of the N400 and LPC components with varying group differences between the spoken
      and signed targets were found. The LPC was the dominant response. The controls'
      LPC differed from the LPC of the two signing groups. It was reduced to the
      auditory unrelated targets and was less frontal for all the visual targets. The
      visual LPC was more broadly distributed in native than non-native signers and was
      left-lateralized for the unrelated targets in the native hearing signers only.
      Semantic priming effects were found for the auditory N400 in all groups, but only
      native hearing signers revealed a clear N400 effect to the visual targets.
      Surprisingly, the non-native signers revealed no semantically-related processing
      effect to the visual targets reflected in the N400 or the LPC; instead they
      appeared to rely more on visual post-lexical analyzing stages than native
      signers. We conclude that native and non-native signers employed different
      processing strategies to integrate signed and spoken semantic content. It
      appeared that the signers' semantic processing system was affected by group
      specific factors like language background and/or usage. 

PMID- 24751995
TI  - Secondary perforating dermatosis in an infant with primary hyperoxaluria type I.

PMID- 24751996
TI  - The rise and fall of a genus: Complete mtDNA genomes shed light on the
      phylogenetic position of yellow-tailed woolly monkeys, Lagothrix flavicauda, and
      on the evolutionary history of the family Atelidae (Primates: Platyrrhini).
AB  - Using complete mitochondrial genome sequences, we provide the first molecular
      analysis of the phylogenetic position of the yellow-tailed woolly monkey,
      Lagothrix flavicauda (a.k.a. Oreonax flavicauda), a critically endangered
      neotropical primate endemic to northern Peru. The taxonomic status and
      phylogenetic position of yellow-tailed woolly monkeys have been debated for many
      years, but in this study both Bayesian and maximum likelihood phylogenetic
      reconstructions unequivocally support a monophyletic woolly monkey clade that
      includes L. flavicauda as the basal taxon within the radiation. Bayesian dating
      analyses using several alternative calibrations suggest that the divergence of
      yellow-tailed woolly monkeys from other Lagothrix occurred in the Pleistocene,
      ~2.1Ma, roughly 6.5 my after the divergence of woolly monkeys from their sister
      genus, Brachyteles. Additionally, comparative analysis of the cytochrome oxidase
      subunit 2 (COX2) gene shows that genetic distances between yellow-tailed woolly
      monkeys and other Lagothrix from across the genus' geographic distribution fall
      well within the range of between-species divergences seen in a large number of
      other platyrrhine primate genera at the same locus and outside the range of
      between-genus divergences. Our results thus confirm a position within Lagothrix
      for the yellow-tailed woolly monkey and strongly suggest that the name Oreonax be
      formally considered a synonym for this genus. This revision in taxonomic status
      does not change the dire conservation threats facing the yellow-tailed woolly
      monkey in Peru, where the remaining wild population is estimated at only ~10,000
      individuals living in a highly fragmented landscape. 

PMID- 24751997
TI  - High-affinity glucose transport in Aspergillus nidulans is mediated by the
      products of two related but differentially expressed genes.
AB  - Independent systems of high and low affinity effect glucose uptake in the
      filamentous fungus Aspergillus nidulans. Low-affinity uptake is known to be
      mediated by the product of the mstE gene. In the current work two genes, mstA and
      mstC, have been identified that encode high-affinity glucose transporter
      proteins. These proteins' primary structures share over 90% similarity,
      indicating that the corresponding genes share a common origin. Whilst the
      function of the paralogous proteins is little changed, they differ notably in
      their patterns of expression. The mstC gene is expressed during the early phases
      of germination and is subject to CreA-mediated carbon catabolite repression
      whereas mstA is expressed as a culture tends toward carbon starvation. In
      addition, various pieces of genetic evidence strongly support allelism of mstC
      and the previously described locus sorA. Overall, our data define MstC/SorA as a
      high-affinity glucose transporter expressed in germinating conidia, and MstA as a
      high-affinity glucose transporter that operates in vegetative hyphae under
      conditions of carbon limitation. 

PMID- 24751999
TI  - Clinical use of fertility agents and risk of breast cancer: a recent update for
      an old problem.
AB  - PURPOSE OF REVIEW: Female infertility is today a very common, expanding problem
      and therefore restoring fertility strategies are increasing in the last few
      years. An association between ovarian stimulation and breast cancer risk has been
      hypothesized, but the question has not yet been clarified. RECENT FINDINGS: In
      the last 2 years, many important studies have been published on this topic. A lot
      of new combinations of drugs are in experimentation and other recent drugs are
      already in current use, such as aromatase inhibitors. Furthermore, the data from
      older studies were investigated by two recent meta-analyses. SUMMARY: Infertility
      affects many couples in western countries and the use of fertility stimulation
      techniques is widespread in the last few years, determining personal anxiety,
      social costs, and organizing difficulties. It is well known that one of the most
      important causative agents for the development of breast cancer is the
      proliferative activity of endogenous and exogenous female hormones. Therefore, it
      seems appropriate to investigate the risk of breast cancer derived from the use
      of hormonal therapies in infertile women. The final clarification of this
      question is very important so that all women can realize their dream of having
      children, with the certainty of not being exposed to an increased risk of breast
      cancer.

PMID- 24751998
TI  - Reproductive impact of MRI-guided focused ultrasound surgery for fibroids: a
      systematic review of the evidence.
AB  - PURPOSE OF REVIEW: Magnetic-resonance-guided focused ultrasound surgery (MRgFUS)
      is a minimally invasive technique for the treatment of uterine fibroids. The
      purpose of this review is to highlight the impact of MRgFUS on fertility and
      reproductive outcomes. RECENT FINDINGS: The role of MRgFUS in the treatment of
      fibroids has been evolving since its introduction in 2004. Several new devices
      and techniques including location-specific treatment, volumetric therapy, and
      vessel-targeted therapy have been introduced over the last few years. Several
      case series report uncomplicated pregnancy following MRgFUS; however, results of
      the ongoing studies will further elucidate the utility of MRgFUS in patients
      planning future fertility. A systematic review of the literature was completed
      and studies that reported quality of life at baseline and after 6 months were
      included in a meta-analysis. SUMMARY: MRgFUS represents a minimally invasive
      treatment for uterine fibroids that is able to improve the quality of life and
      fibroid size with durability. It is possible that MRgFUS could be the treatment
      of choice for patients desiring future fertility; however, further investigation
      is needed.

PMID- 24752000
TI  - Is the fertility treatment itself a risk factor for early pregnancy loss?
AB  - PURPOSE OF REVIEW: With the recent advancements in reproductive medicine, many
      infertile couples now have the opportunity to conceive their own biological
      children. Although some medication protocols, such as clomiphene citrate, have
      been utilized for decades, other treatment modalities have evolved over the
      recent years. It therefore becomes imperative to assess the outcomes of these
      modalities and be critical regarding their safety. Pregnancy loss is one outcome
      that can affect many couples who conceive both spontaneously and with assistance
      via fertility treatment. In this review, several of the most commonly used
      fertility treatments will be discussed and the impact, if any, they may have in
      early pregnancy loss will be addressed. RECENT FINDINGS: Current data do not
      support that notion that infertility treatments or assisted reproductive
      techniques contribute to early pregnancy loss. However, more studies are needed
      to eliminate the confounding variables that make data interpretation difficult to
      generalize to the infertile population. SUMMARY: An early pregnancy loss can
      cause emotional distress and grief, particularly for couples already dealing with
      an infertility diagnosis. Therefore, knowledge regarding the relationship between
      infertility and early pregnancy loss is vital in order to properly counsel the
      couple prior to starting treatment.

PMID- 24752001
TI  - Time-lapse embryo imaging technology: does it improve the clinical results?
AB  - PURPOSE OF REVIEW: The purpose of the review is to summarize recent developments
      in time-lapse technologies and early embryo morphokinetics and to discuss their
      impact on current clinical outcomes. RECENT FINDINGS: Contemporary embryo culture
      and selection methodologies that are based on classical morphology are clearly
      limited in providing the most suitable embryo for a successful pregnancy.
      Noninvasive observation of embryo development by capturing the images with a time
      lapse device has recently been proposed to be a better method of embryo viability
      assessment. Such methodologies have been shown to increase the quality and the
      quantity of information on the viability without disturbing the culture
      conditions. SUMMARY: Commercial availability of different time-lapse devices for
      human embryos facilitated the use of morphokinetics as an additional tool in
      human embryo selection. The application of such technologies has already shown
      positive results on clinical outcome by increasing our scope of traditional
      embryo selection, leading to higher implantation and clinical pregnancy rates.
      Additional benefit can come from the less-disturbed incubation environment that
      is created by all-in-one incubators. Such devices can also be very important
      research tools in order to observe and analyze the effect of different patient
      specific or clinical conditions on embryo development parameters that are not
      available through classical embryo scoring.

PMID- 24752002
TI  - In-vitro maturation of germinal vesicle and metaphase I eggs prior to
      cryopreservation optimizes reproductive potential in patients undergoing
      fertility preservation.
AB  - PURPOSE OF REVIEW: To evaluate current and previous findings related to a timely
      implementation of in-vitro maturation (IVM) of germinal vesicle, metaphase I and
      metaphase II oocytes with an optimal cryopreservation to determine whether IVM
      should be attempted prior to (fresh IVM) or IVM after cryopreservation (postthaw
      IVM). Mitochondrion, chromatin and spindle formation in both groups were
      interpreted from referenced studies to establish best management of all oocytes.
      RECENT FINDINGS: The postthaw survival of germinal vesicle, metaphase I, fresh
      IVM-metaphase II and control metaphase II oocytes did not differ significantly
      [83.3% (n=9), 86.7% (n=12), 83% (n=57) and 86% (n=68), respectively]. Overall,
      combined survival and maturation were significantly higher (P<0.05) in the fresh
      IVM group at 63.8% (44 of 69) compared with the postthaw IVM group at 33.3% (nine
      of 27). SUMMARY: Conservation of retrieved immature oocytes after vaginal oocyte
      retrieval has become a major concern for patients, as they strive to maximize the
      reproductive viability of all oocytes obtained during treatment. Oocyte
      cryopreservation is important for patients at risk of ovarian cancer, elective
      fertility preservation and potentially for ovum donation. The superior maturation
      rate of germinal vesicle and metaphase I oocytes in the fresh IVM vs. postthaw
      groups provides strong impetus to mature oocytes to the metaphase II stage prior
      to cryopreservation.

PMID- 24752004
TI  - The impact of lifestyle behaviors on infertility treatment outcome.
AB  - PURPOSE OF REVIEW: The impact of lifestyle behaviors on fertility is poorly
      understood, as is the impact of specific behaviors on the advanced reproductive
      technologies. It is vital for healthcare professionals to understand which
      lifestyle behaviors can have the greatest negative impact in an effort to improve
      patient recommendations. The purpose of this article is to review the recent
      research on this topic. RECENT FINDINGS: The majority of research in this area is
      epidemiological; there are a few randomized controlled trials (RCTs) regarding
      weight loss in infertility patients, but no RCTs on other lifestyle behaviors.
      High or low BMI, alcohol, vigorous exercise, nicotine, and antidepressant
      medications may have an adverse impact on fertility. It is unclear whether
      dietary supplements can have a positive impact on fertility. Patients do not
      appear to follow recommendations for lifestyle behavior modifications during
      infertility treatment. SUMMARY: Healthcare professionals need to be more
      effective in making lifestyle behavior recommendations for infertility patients,
      including those receiving treatment. VIDEO ABSTRACT:
      http://links.lww.com/COOG/A13.

PMID- 24752003
TI  - The impact of assisted reproductive technologies on genomic imprinting and
      imprinting disorders.
AB  - PURPOSE OF REVIEW: Genomic imprinting refers to preferential allele-specific gene
      expression. DNA methylation-based molecular mechanisms regulate establishment and
      maintenance of parental imprints during early embryo development and
      gametogenesis. Because of the coincident timing, a potential association between
      assisted reproductive technology (ART) procedures and imprinting defects has been
      investigated in various studies. In this review, we provide an overview of
      genomic imprinting and present a summary of the relevant clinical data. RECENT
      FINDINGS: ART procedures affect DNA methylation pattern, parental imprinting
      status, and imprinted gene expression in the mouse embryo. In humans, several
      case series suggested an association between ART and imprinting disorders, with a
      three-fold to six-fold higher prevalence of ART use among children born with
      Beckwith-Wiedemann syndrome compared to the general population. However, more
      recent studies failed to support these findings and could not demonstrate an
      association between imprinting disorders and ARTs, independent of subfertility.
      SUMMARY: ART procedures may affect methylation status of imprinted regions in the
      DNA, leading to imprinting disorders. Although the low prevalence of imprinting
      disorders makes it challenging to perform conclusive clinical trials, further
      studies in large registries are required to determine the real impact of ARTs on
      their occurrence.

PMID- 24752005
TI  - Use of fertility drugs and risk of ovarian cancer.
AB  - PURPOSE OF REVIEW: The purpose of this review is to highlight recent research and
      insights into the relationship between fertility drug use and ovarian cancer
      risk. RECENT FINDINGS: Results from two large case-control studies provided
      further evidence that fertility drug use does not significantly contribute to
      risk of ovarian cancer among the majority of women when adjusting for known
      confounding factors. However, questions regarding the effect on certain
      subgroups, including long-term fertility drug users, women who remain nulligravid
      after fertility treatment, women with BRCA1 or BRCA2 mutations and borderline
      ovarian tumours, still remain. In addition, it may currently just be too early to
      determine whether there is an association between fertility drug use and ovarian
      cancer risk given that many of the exposed women are only now beginning to reach
      the ovarian cancer age range. SUMMARY: Whether use of fertility drugs increases
      the risk of ovarian cancer is an important question that requires further
      investigation, in particular given the large number of women utilizing fertility
      treatments. Fortunately, results from recent studies have been mainly reassuring.
      Large well designed studies with sufficient follow-up time are needed to further
      evaluate the effects of fertility treatments within subgroups defined by patient
      and tumour characteristics.

PMID- 24752006
TI  - Safety and Immunogenicity of a Mycoplasma ovipneumoniae bacterin for domestic
      sheep (Ovis aries).
AB  - BACKGROUND: Mortality from epizootic pneumonia is hindering re-establishment of
      bighorn sheep populations in western North America. Mycoplasma ovipneumoniae, a
      primary agent of this disease, is frequently carried asymptomatically by the
      domestic sheep and goats that constitute the reservoir of this agent for
      transmission to bighorn sheep. Our long-term objective is to reduce the risk of
      M. ovipneumoniae infection of bighorn sheep; one approach to this objective is to
      control the pathogen in its reservoir hosts. METHODS: The safety and
      immunogenicity of M. ovipneumoniae for domestic sheep was evaluated in three
      experimental immunization protocols: 1) live M. ovipneumoniae (50 ug protein); 2)
      killed M. ovipneumoniae (50 ug whole cell protein) in oil adjuvant; and 3) killed
      M. ovipneumoniae (250 ug whole cell protein) in oil adjuvant. Immunogenicity was
      assessed by two serum antibody measures: competitive enzyme-linked immunosorbent
      assay (cELISA) (experiments 1-3) and serum growth inhibition (Experiment 3).
      Passive immunogenicity was also assessed in the third experiment using the same
      assays applied to blood samples obtained from the lambs of immunized ewes.
      RESULTS AND CONCLUSIONS: Adverse reactions to immunization were generally minor,
      but local reactions were regularly observed at immunization sites with bacterins
      in oil adjuvants. No evidence of M. ovipneumoniae specific antibody responses
      were observed in the first or second experiments and no resistance to
      colonization was observed in the first experiment. However, the ewes in the third
      experiment developed strong cELISA serum antibody responses and significant serum
      M. ovipneumoniae inhibition activity, and these responses were passively
      transferred to their lambs. The results of these trials indicate that
      immunization with relatively large antigenic mass combined with an adjuvant is
      capable of inducing strong active antibody responses in ewes and passively
      immunizing lambs.

PMID- 24752007
TI  - Human papillomavirus and cystic node metastasis in oropharyngeal cancer and
      cancer of unknown primary origin.
AB  - The clinical significance of human papillomavirus (HPV) in neck node metastasis
      from cancer of unknown primary (CUP) is not well established. We aimed to address
      the relationship of HPV status between node metastasis and the primary tumor, and
      also the relevance of HPV status regarding radiographically detected cystic node
      metastasis in head and neck squamous cell carcinoma (HNSCC) and CUP. HPV DNA was
      examined in 68 matched pairs of node metastasis and primary tumor, and in node
      metastasis from 27 CUPs. In surgically treated CUPs, p16 was examined
      immunohistochemically. When tonsillectomy proved occult tonsillar cancer in CUP,
      HPV DNA and p16 were also examined in the occult primary. Cystic node metastasis
      on contrast-enhanced computed tomography scans was correlated with the primary
      site and HPV status in another series of 255 HNSCCs and CUPs with known HPV
      status. Node metastasis was HPV-positive in 19/37 (51%) oropharyngeal SCCs
      (OPSCCs) and 10/27 (37%) CUPs, but not in non-OPSCCs. Fluid was collected from
      cystic node metastasis using fine needle aspiration in two OPSCCs and one CUP,
      and all fluid collections were HPV-positive. HPV status, including the presence
      of HPV DNA, genotype, and physical status, as well as the expression pattern of
      p16 were consistent between node metastasis and primary or occult primary tumor.
      Occult tonsillar cancer was found more frequently in p16-positive CUP than in p16
      negative CUP (odds ratio (OR), 39.0; 95% confidence interval (CI), 1.4-377.8; P =
      0.02). Radiographically, cystic node metastasis was specific to OPSCC and CUP,
      and was associated with HPV positivity relative to necrotic or solid node
      metastasis (OR, 6.2; 95% CI, 1.2-45.7; P = 0.03). In conclusion, HPV status
      remains unchanged after metastasis. The occult primary of HPV-positive CUP is
      most probably localized in the oropharynx. HPV status determined from fine needle
      aspirates facilitates the diagnosis of cystic node metastasis. 

PMID- 24752008
TI  - Intravitreal dexamethasone implant for refractory macular edema secondary to
      vitrectomy for macular pucker.
AB  - PURPOSE: To study the efficacy of a single 0.7 mg dexamethasone intravitreal
      implant in vitrectomized eyes with refractory macular edema secondary to combined
      cataract extraction and macular pucker removal. METHODS: In 8 eyes of 8
      consecutive patients with refractory macular edema secondary to combined cataract
      extraction and 25-gauge vitrectomy with internal limiting membrane peeling for
      macular pucker removal, the injection of the 0.7 mg dexamethasone implant was
      performed. Best-corrected visual acuity, central retinal thickness measured by
      spectral domain optical coherence tomography, and intraocular pressure were
      evaluated at baseline, 1 month, and 6 months. RESULTS: After a mean follow-up of
      6.75 +/- 0.71 months, best-corrected visual acuity was significantly increased (P
      < 0.0001) from 20/50 to 20/23 (P < 0.0001), mean central retinal thickness
      decreased significantly from 439 +/- 45 MUm to 296 +/- 49 MUm (P < 0.0001), and
      intraocular pressure changed significantly (P = 0.02) from 14.63 +/- 1.19 to 16
      +/- 0.93. In no case postoperative hypotony or other complication was observed.
      CONCLUSION: A single injection of the 0.7 mg dexamethasone intravitreal implant
      resulted effective in the treatment of refractory macular edema secondary to
      combined cataract extraction and vitrectomy for macular pucker removal allowing a
      stable visual acuity recovery.

PMID- 24752009
TI  - Cryotherapy-induced release of epiretinal membrane associated with retinal
      vasoproliferative tumor: analysis of 16 cases.
AB  - PURPOSE: To evaluate epiretinal membrane (ERM) response after cryotherapy for
      retinal vasoproliferative tumors (VPTs). METHOD: Retrospective interventional
      case series. RESULTS: Of 16 eyes with VPT and ERM, the tumor was classified as
      primary in 12 (75%) eyes or secondary in 4 (25%) eyes. The median patient age was
      44 years (mean, 43 years; range, 9-70 years). The tumor was located in
      extramacular zone (n = 16, 100%) and inferotemporal quadrant (n = 12, 75%). The
      mean tumor base was 6 mm, and thickness was 3 mm. The ERM involved the macula in
      12 (75%) eyes and extramacular zone in 4 (25%) eyes, with best-corrected visual
      acuity of 20/40 or better in 6 (38%) eyes. Associated features included cystoid
      macular edema (n = 8, 50%), subretinal fluid (n = 10, 63%), vitreous cells (n =
      9, 56%), and vitreous hemorrhage (n = 7, 44%). Single-session cryotherapy (double
      freeze-thaw) to the VPT was performed in each case. Over mean follow-up of 68
      months (median, 54 months; range, 8-252 months), tumor regression was documented
      in 16 (100%) cases, with ERM release in 10 (63%) cases. After ERM release, the
      foveal anatomy was normal in 12 (75%) eyes. Final visual acuity improved (n = 5,
      31%), remained stable (n = 9, 56%), or worsened (n = 2, 13%). Posttreatment best
      corrected visual acuity was 20/40 or better in 10 (63%) eyes. CONCLUSION:
      Cryotherapy is remarkably effective for VPT of 6 mm or less in basal dimension.
      After cryotherapy, VPT-related ERM spontaneously released in 63% of the cases,
      without the need for surgical intervention.

PMID- 24752011
TI  - Projected range contractions of European protected oceanic montane plant
      communities: focus on climate change impacts is essential for their future
      conservation.
AB  - Global climate is rapidly changing and while many studies have investigated the
      potential impacts of this on the distribution of montane plant species and
      communities, few have focused on those with oceanic montane affinities. In
      Europe, highly sensitive bryophyte species reach their optimum occurrence,
      highest diversity and abundance in the north-west hyperoceanic regions, while a
      number of montane vascular plant species occur here at the edge of their range.
      This study evaluates the potential impact of climate change on the distribution
      of these species and assesses the implications for EU Habitats Directive
      protected oceanic montane plant communities. We applied an ensemble of species
      distribution modelling techniques, using atlas data of 30 vascular plant and
      bryophyte species, to calculate range changes under projected future climate
      change. The future effectiveness of the protected area network to conserve these
      species was evaluated using gap analysis. We found that the majority of these
      montane species are projected to lose suitable climate space, primarily at lower
      altitudes, or that areas of suitable climate will principally shift northwards.
      In particular, rare oceanic montane bryophytes have poor dispersal capacity and
      are likely to be especially vulnerable to contractions in their current climate
      space. Significantly different projected range change responses were found
      between 1) oceanic montane bryophytes and vascular plants; 2) species belonging
      to different montane plant communities; 3) species categorised according to
      different biomes and eastern limit classifications. The inclusion of
      topographical variables in addition to climate, significantly improved the
      statistical and spatial performance of models. The current protected area network
      is projected to become less effective, especially for specialised arctic-montane
      species, posing a challenge to conserving oceanic montane plant communities.
      Conservation management plans need significantly greater focus on potential
      climate change impacts, including models with higher-resolution species
      distribution and environmental data, to aid these communities' long-term
      survival. 

PMID- 24752010
TI  - Outer retinal structure after closed-globe blunt ocular trauma.
AB  - PURPOSE: To evaluate outer retinal structural abnormalities in patients with
      visual deficits after closed-globe blunt ocular trauma. METHODS: Nine subjects
      with visual complaints after closed-globe blunt ocular trauma were examined
      between 1 month after trauma and 6 years after trauma. Spectral domain optical
      coherence tomography was used to assess the outer retinal architecture, whereas
      adaptive optics scanning light ophthalmoscopy was used to analyze the
      photoreceptor mosaic integrity. RESULTS: Visual deficits ranged from central
      scotomas to decreased visual acuity. Spectral domain optical coherence tomography
      defects included focal foveal photoreceptor lesions, variable attenuation of the
      interdigitation zone, and mottling of the outer segment band, with one subject
      having normal outer retinal structure. Adaptive optics scanning light
      ophthalmoscopy revealed disruption of the photoreceptor mosaic in all subjects,
      variably manifesting as foveal focal discontinuities, perifoveal hyporeflective
      cones, and paracentral regions of selective cone loss. CONCLUSION: We observe
      persistent outer retinal disruption in subjects with visual complaints after
      closed-globe blunt ocular trauma, albeit to a variable degree. Adaptive optics
      scanning light ophthalmoscopy imaging allows the assessment of photoreceptor
      structure at a level of detail not resolvable using spectral domain optical
      coherence tomography or other current clinical imaging tools. Multimodal imaging
      seems to be useful in revealing the cause of visual complaints in patients after
      closed-globe blunt ocular trauma. Future studies are needed to better understand
      how photoreceptor structure changes longitudinally in response to various
      traumas.

PMID- 24752012
TI  - Hepatic HMOX1 expression positively correlates with Bach-1 and miR-122 in
      patients with HCV mono and HIV/HCV coinfection.
AB  - AIM: To analyze the expression of HMOX1 and miR-122 in liver biopsy samples
      obtained from HCV mono-and HIV/HCV co-infected patients in relation to selected
      clinical parameters, histological examination and IL-28B polymorphism as well as
      to determine whether HMOX1 expression is dependent on Bach-1. MATERIALS AND
      METHODS: The study group consisted of 90 patients with CHC: 69 with HCV mono and
      21 with HIV/HCV co-infection. RT-PCR was used in the analysis of HMOX1, Bach-1
      and miR-122 expression in liver biopsy samples and in the assessment of IL-28B
      single-nucleotide polymorphism C/T (rs12979860) in the blood. Moreover in liver
      biopsy samples an analysis of HO-1 and Bach-1 protein level by Western Blot was
      performed. RESULTS: HCV mono-infected patients, with lower grading score (G<2)
      and higher HCV viral load (>600000 IU/mL) demonstrated higher expression of
      HMOX1. In patients with HIV/HCV co-infection, the expression of HMOX1 was lower
      in patients with lower lymphocyte CD4 count and higher HIV viral load. IL28B
      polymorphism did not affect the expression of either HMOX1 or miR-122. Higher
      HMOX1 expression correlated with higher expression of Bach-1 (Spearman's rho =
      0.586, p = 0.000001) and miR-122 (Spearman's rho = 0.270, p = 0.014059).
      CONCLUSIONS: HMOX1 and miR-122 play an important role in the pathogenesis of CHC
      in HCV mono-and HIV/HCV co-infected patients. Reduced expression of HMOX1 in
      patients with HIV/HCV co-infection may indicate a worse prognosis in this group.
      Our results do not support the importance of Bach-1 in repression of HMOX1 in
      patients with chronic hepatitis C.

PMID- 24752013
TI  - Immunogenicity of anti-tumour necrosis factor therapy in Korean patients with
      rheumatoid arthritis and ankylosing spondylitis.
AB  - The aim of this study was to investigate the prevalence of antidrug antibodies
      (ADAs) against tumour necrosis factor (TNF) inhibitors in patients with
      rheumatoid arthritis (RA) and ankylosing spondylitis (AS). ADAs were detected in
      18 (9.8%) patients with RA and in 18 (10.2%) patients with AS of the 360
      patients. Development of ADAs was significantly associated with treatment failure
      in RA patients (P=0.003). When classified by drugs, the prevalence of
      immunogenicity in descending order was 17 (28.8%) patients treated with
      infliximab, 17 (10.4%) with adalimumab, and 2 (1.4%) with etanercept. After
      adjustment for disease and duration of anti-TNF therapy, the odds ratio as a
      reference of adalimumab-treated patients was 9.159 (95% confidence interval [CI]
      2.005-41.845) for infliximab and 0.280 (95% CI 0.128-0.611) for etanercept. The
      immunogenicity of anti-TNF therapy was highest in the infliximab-treated group
      and significantly lower in the etanercept-treated group. 

PMID- 24752015
TI  - Chronic kidney disease. Walking reduces inflammation in predialysis CKD.

PMID- 24752016
TI  - 25 Years and counting.

PMID- 24752017
TI  - Pharmacotherapy during the end of life: caring for the actively dying patient.

PMID- 24752014
TI  - Proteostasis in endoplasmic reticulum--new mechanisms in kidney disease.
AB  - Cells use an exquisite network of mechanisms to maintain the integrity and
      functionality of their protein components. In the endoplasmic reticulum (ER),
      these networks of protein homeostasis--referred to as proteostasis--regulate
      protein synthesis, folding and degradation via the unfolded protein response
      (UPR) pathway. The UPR pathway has two components: the adaptive UPR pathway,
      which predominantly maintains the ER function or ER proteostasis, and the
      apoptotic UPR pathway, which eliminates dysfunctional cells that have been
      subject to long-term or severe ER stress. Dysregulation of the UPR pathway often
      occurs in glomerular or tubulointerstitial cells under a pathogenic
      microenvironment, such as oxidative stress, glycative stress or hypoxia. A
      defective UPR is highly deleterious to renal cell function and viability and is
      thereby implicated in the pathophysiology of various kidney diseases.
      Accumulating evidence provides a link between the UPR pathway and mitochondrial
      structure and function, indicating the important role of ER proteostasis in the
      maintenance of mitochondrial homeostasis. Restoration of normal proteostasis,
      therefore, holds promise in protecting the kidney from pathogenic stresses as
      well as ageing. This Review is focused on the role of the ER stress and UPR
      pathway in the maintenance of ER proteostasis, and highlights the involvement of
      the derangement of ER proteostasis and ER stress in various pathogenic stress
      signals in the kidney.

PMID- 24752019
TI  - Health information technology safety: the perfect storms.

PMID- 24752020
TI  - Three structures for a healthy work environment.

PMID- 24752021
TI  - Case report: pulmonary edema induced by breath holding in an adolescent patient.

PMID- 24752022
TI  - Improving nurses' knowledge of continuous ST-segment monitoring.
AB  - BACKGROUND: Continuous ST-segment monitoring can result in detection of
      myocardial ischemia, but in clinical practice, continuous ST-segment monitoring
      is conducted incorrectly and underused by many registered nurses (RNs). Many RNs
      are unable to correctly institute ST-segment monitoring guidelines because of a
      lack of education. PURPOSE: To evaluate whether an educational intervention,
      provided to 32 RNs, increases knowledge and correct clinical decision making
      (CDM) for the use of continuous ST-segment monitoring. METHODS: At a single
      institution, an ST-segment monitoring class was provided to RNs in 2
      cardiovascular units. Knowledge and correct CDM instruments were used for a
      baseline pretest and subsequent posttest after ST-segment monitoring education.
      RESULTS: Statistical significance between pretest and posttest scores for
      knowledge and correct CDM practice was noted with dependent t tests (P = .0001).
      CONCLUSIONS: Many RNs responsible for electrocardiographic monitoring are not
      aware of evidence-based ST-segment monitoring practice guidelines and cannot
      properly place precordial leads needed for ST-segment monitoring. Knowledge and
      correct CDM with ST-segment monitoring can be improved with focused education.

PMID- 24752023
TI  - Sedative and analgesic use on night and day shifts in a pediatric cardiovascular
      intensive care unit.
AB  - INTRODUCTION: The use of sedative and analgesic medications is directly linked to
      patient outcomes. The practice of administering as-needed sedative or analgesic
      medications deserves further exploration. We hypothesized that important
      variations exist in the practice of administering as-needed medications in the
      intensive care unit (ICU). We aimed to determine the influence of time of day on
      the practice of administering as-needed sedative or analgesic medications to
      children in the ICU. METHODS: Medication administration records of patients
      admitted to our pediatric cardiovascular ICU during a 4-month period were
      reviewed to determine the frequency and timing of as-needed medication usage by
      shift. RESULTS: A total of 152 ICU admissions (1854 patient days) were reviewed.
      A significantly greater number of as-needed doses were administered during the
      night shift (fentanyl, P = .005; lorazepam, P = .03; midazolam, P = .0003;
      diphenhydramine, P = .0003; and chloral hydrate, P = .0006). These differences
      remained statistically significant after excluding doses given during the first 6
      hours after cardiovascular surgery. Morphine administration was similar between
      shifts (P = .08). CONCLUSIONS: We identified a pattern of increased
      administration of as-needed sedative or analgesic medications during nights.
      Further research is needed to identify the underlying causes of this practice
      variation.

PMID- 24752024
TI  - Guidelines review and update.

PMID- 24752025
TI  - Cardiac advanced life support-surgical guideline: overview and implementation.
AB  - Cardiac arrest in the immediate postoperative recovery period in a patient who
      underwent cardiac surgery is typically related to reversible causes-tamponade,
      bleeding, ventricular arrhythmias, or heart blocks associated with conduction
      problems. When treated promptly, 17% to 79% of patients who experience cardiac
      arrest after cardiac surgery survive to discharge. The Cardiac Advanced Life
      Support-Surgical (CALS-S) guideline provides a standardized algorithm approach to
      resuscitation of patients who experience cardiac arrest after cardiac surgery.
      The purpose of this article is to discuss the CALS-S guideline and how to
      implement it. 

PMID- 24752026
TI  - Clinical review and implications of the guideline for the early management of
      patients with acute ischemic stroke.
AB  - Stroke is the fourth leading cause of death and the leading cause of significant,
      long-term disability in the United States. Clinicians' knowledge and use of
      evidence to guide the care of patients with ischemic stroke are paramount to
      improving patient outcomes. The recently updated "Guidelines for the Early
      Management of Patients With Acute Ischemic Stroke: A Guideline for Healthcare
      Professionals From the American Heart Association/American Stroke Association"
      provides clinicians with evidence-based, expert consensus to guide the
      recognition and early management of patients with acute ischemic stroke. The
      guideline provides 115 recommendations for the management of patients with acute
      ischemic stroke, including 24 new recommendations and 51 revised recommendations
      divided into 14 major topic areas. This article reviews the recommendations and
      related literature and provides suggestions for use and implementation of the
      guideline within a stroke program of care. 

PMID- 24752027
TI  - Synopsis and Review of the American College of Cardiology Foundation/American
      Heart Association 2013 ST-Elevation Myocardial Infarction Guideline.
AB  - The "2013 ACCF/AHA Guideline for the Management of ST-Elevation Myocardial
      Infarction: A Report of the American College of Cardiology Foundation/American
      Heart Association Task Force on Practice Guidelines" is a major revision of the
      2004 guideline. This article provides a synopsis and review of the guideline
      focusing on changes in patient care and implementing processes to ensure quality
      care. The implementation of this guideline provides nursing with a unique
      opportunity to affect patients and families primarily by recognition of the event
      and education about lifestyle modification and disease management.
      Regionalization of emergency systems provides a novel situation for nursing to
      develop interdepartmental and system protocols. 

PMID- 24752028
TI  - Comprehensive guideline for care of patients with heart failure.
AB  - Heart failure (HF) is a complex clinical syndrome that results from any
      structural or functional impairment of ventricular filling or ejection of blood.
      More than 5.1 million people are living with HF in the United States today. This
      number will continue to rise with the increase in the aging population. With so
      many people living with HF, nurses need to be well versed on how best to care for
      them. The 2013 American College of Cardiology Foundation/American Heart
      Association guideline for the management of HF is a comprehensive guide for all
      clinicians caring for patients with HF. The updated guideline was developed to
      assist providers in decision making in the diagnosis and treatment of HF. The
      goals of the writing committee were to improve quality of care for patients with
      HF, optimize their outcomes, and improve the efficient use of various resources
      in the treatment of patients with HF. 

PMID- 24752029
TI  - Ventilator-associated pneumonia bundle: reconstruction for best care.
AB  - The ventilator-associated pneumonia (VAP) bundle is a focus of many health care
      institutions. Many hospitals are conducting process-improvement projects in an
      attempt to improve VAP rates by implementing the bundle. However, this bundle is
      controversial in the literature, because the evidence supporting the VAP
      interventions is weak. In addition, definitions used for surveillance are
      interpreted differently than definitions used for clinical diagnosis. The
      variance in definitions has led to lower reported VAP rates, which may not be
      accurate. Because of the variance in definitions, the Centers for Disease Control
      and Prevention developed a ventilator-associated event algorithm. Health care
      institutions are under pressure to reduce the VAP infection rate, but correctly
      identifying VAP can be very challenging. This article reviews the current
      evidence related to VAP and provides insight into implementing a suggested
      revision of the care of patients being treated with mechanical ventilation. 

PMID- 24752031
TI  - Targeting sepsis as a performance improvement metric: role of the nurse.
AB  - Sepsis is the body's systemic response to infection that can be complicated by
      acute organ dysfunction and is associated with high mortality rates and adverse
      outcomes for acute and critically ill patients. The 2012 Surviving Sepsis
      Campaign guidelines advocated for implementation of evidence-based practice care
      for sepsis, with a focus on quality improvement. Nurses are directly involved in
      identification and management of sepsis. Implementing performance improvement
      strategies aimed at early recognition and targeted treatment can further improve
      sepsis care and patient outcomes. This article presents an overview of the
      process of implementing performance improvement initiatives for sepsis care,
      highlighting the significant contribution of nursing care. 

PMID- 24752032
TI  - Cardiac monitoring and electrode placement revisited.

PMID- 24752033
TI  - The channel-kinase TRPM7, revealing the untold story of Mg(2+) in cellular
      signaling.
AB  - Ion homeostasis dysregulations have severe effects on human health, impairing the
      effectiveness and appropriateness of major cellular events, including immune
      responses. The adverse effects of Mg(2+) deficiency on cellular physiology are
      well known and documented, but mechanistic insights into Mg(2+) sensitive signal
      transduction are still lacking. TRPM7 and its sister channel TRPM6 stand out as
      the only known fusions of an ion pore with a Ser/Thr kinase domain. Both channels
      are permeable to divalent cations and are central regulators of Mg(2+)
      homeostasis. One crucial aspect of TRPM7 function we have extensively studied is
      the relationship between its ion channel portion and its C-terminal Ser/Thr
      kinase domain. The modulation of ion channels by phosphorylation through
      exogenous kinases is common, however the covalent bound between the TRPM7 channel
      and its kinase suggests a novel kind of link between ion-entry and signal
      transduction events. Current knowledge supports a reciprocal "two-way street"
      model where TRPM7-kinase modulates ion transport function through Ser/Thr
      phosphorylation, and in turn, channel gating and ionic conditions in close
      proximity to the pore regulate TRPM7-kinase mediated signaling. We have shown
      that TRPM7 acts as a sensor of Mg(2+)-availability, adjusting key cellular
      functions such as the rate of cellular protein translation to the Mg(2+)
      nutritional status. Since molecular mechanisms controlling rates of protein
      translation are critical for cell growth and division in response to nutrient
      availability, this could have relevance for example for therapies targeted at
      molecules shaping the cancerous translational apparatus. In our quest to
      understand the biology of Mg(2+) in the context of immune responses, we found
      that TRPM7 associates with, and phosphorylates phospholipase C gamma 2
      (PLCgamma2), a pivotal molecule in the signaling pathway following B-cell
      receptor (BCR) activation. This contributes to the Mg(2+)-dependent modulation of
      the Ca(2+) response elicited by BCR ligation, and provides the first molecular
      pathway underlying the Mg(2+)-sensitivity of immune responses. Expanding our
      knowledge about the modulation of immunoreceptor signaling in response to Mg(2+)
      availability could allow for the development of unexplored strategies for
      therapeutic intervention in autoimmune diseases, immunodeficiencies, and
      lymphoma. 

PMID- 24752034
TI  - Effects of motive-oriented therapeutic relationship in a ten-session general
      psychiatric treatment of borderline personality disorder: a randomized controlled
      trial.
AB  - BACKGROUND: Motive-oriented therapeutic relationship (MOTR) was postulated to be
      a particularly helpful therapeutic ingredient in the early treatment phase of
      patients with personality disorders, in particular with borderline personality
      disorder (BPD). The present randomized controlled study using an add-on design is
      the first study to test this assumption in a 10-session general psychiatric
      treatment with patients presenting with BPD on symptom reduction and therapeutic
      alliance. METHODS: A total of 85 patients were randomized. They were either
      allocated to a manual-based short variant of the general psychiatric management
      (GPM) treatment (in 10 sessions) or to the same treatment where MOTR was
      deliberately added to the treatment. Treatment attrition and integrity analyses
      yielded satisfactory results. RESULTS: The results of the intent-to-treat
      analyses suggested a global efficacy of MOTR, in the sense of an additional
      reduction of general problems, i.e. symptoms, interpersonal and social problems
      (F1, 73 = 7.25, p < 0.05). However, they also showed that MOTR did not yield an
      additional reduction of specific borderline symptoms. It was also shown that a
      stronger therapeutic alliance, as assessed by the therapist, developed in MOTR
      treatments compared to GPM (Z55 = 0.99, p < 0.04). CONCLUSIONS: These results
      suggest that adding MOTR to psychiatric and psychotherapeutic treatments of BPD
      is promising. Moreover, the findings shed additional light on the perspective of
      shortening treatments for patients presenting with BPD.

PMID- 24752036
TI  - Genetic overlap between ADHD symptoms and EEG theta power.
AB  - Biological markers that are grounded in neuroscience may facilitate understanding
      of the pathophysiology of complex psychiatric disorders. One of the most
      consistent and robust neural abnormalities in attention deficit hyperactivity
      disorder (ADHD) is increased EEG power in the theta band at rest (4-8Hz). The
      present study used a twin design to estimate the extent of genetic overlap
      between increased theta power and risk for ADHD in order to validate theta power
      as a marker of genetic risk for ADHD. At rest, EEG was measured in 30 monozygotic
      and dizygotic adolescent twin pairs concordant or discordant for high ADHD
      symptom scores and 37 monozygotic and dizygotic control twin pairs with low ADHD
      symptom scores. Structural equation modelling was used to estimate the
      heritability of theta power and partition the genetic and environmental
      contributions to the overlap between ADHD and theta power. A significant
      phenotypic correlation between ADHD symptoms and elevated theta power was found.
      Theta power demonstrated moderate to high heritability estimates (0.77) and
      moderate genetic correlations with ADHD (0.35) suggesting shared genetic
      influences. Increased theta power is a candidate biological marker of genetic
      risk for ADHD, which warrants further investigation of the neurobiological
      mechanisms that underlie the genetic relationship. 

PMID- 24752035
TI  - Saccade reprogramming in Friedreich ataxia reveals impairments in the cognitive
      control of saccadic eye movement.
AB  - Although cerebellar dysfunction has known effects on motor function in Friedreich
      ataxia (FRDA), it remains unclear the extent to which the reprogramming of eye
      movements (saccades) and inhibition of well-learned automatic responses are
      similarly compromised in affected individuals. Here we examined saccade
      reprogramming to assess the ability of people with FRDA to respond toward
      unexpected changes in either the amplitude or direction of an "oddball" target.
      Thirteen individuals with genetically confirmed FRDA and 12 age-matched controls
      participated in the study. The saccade reprogramming paradigm was used to examine
      the effect of an unpredictable "oddball" target on saccade latencies and accuracy
      when compared to a well-learned sequence of reciprocating movements. Horizontal
      eye movements were recorded using a scleral search coil eye tracking technique.
      The results showed a proportionally greater increase in latencies for
      reprogrammed saccades toward an oddball-direction target in the FRDA group when
      compared to controls. The FRDA group were also less accurate in primary saccade
      gain (i.e. ratio of saccade amplitude to target amplitude) when reprogramming
      saccades toward an unexpected change in direction. No significant group
      differences were found on any of the oddball-amplitude targets. Significant
      correlations were revealed between latency and disease severity as measured by
      the Friedreich Ataxia Rating Scale. These findings provide further support to the
      view that cognitive changes in FRDA may arise from disruption of cerebellar
      connections to cortical structures. 

PMID- 24752037
TI  - Prediction of preeclampsia by mean arterial pressure at 11-13 and 20-24 weeks'
      gestation.
AB  - OBJECTIVES: To assess the performance of screening for preeclampsia (PE) by mean
      arterial pressure (MAP) at 11-13 and at 20-24 weeks' gestation. METHODS: MAP was
      measured at 11-13 and 20-24 weeks in 17,383 singleton pregnancies, including 70
      with early PE, requiring delivery <34 weeks' gestation, 143 with preterm PE,
      delivering <37 weeks and 537 with total PE. MAP was expressed as multiple of the
      median (MoM) after adjustment for maternal characteristics and corrected for
      adverse pregnancy outcomes. The performance of screening for PE by maternal
      characteristics and MAP MoM at 11-13 weeks (MAP-1), MAP MoM at 20-24 weeks (MAP
      2) and their combination was evaluated. RESULTS: In screening by maternal
      characteristics and MAP-1, at a false-positive rate (FPR) of 10%, the detection
      rates (DR) of early PE, preterm PE and total PE were 74.3, 62.9 and 49.3%,
      respectively; the DR at FPR of 5% were 52.9, 42.7 and 35.8%. In screening by MAP
      1 and MAP-2 the DR at FPR of 10%, were 84.3, 65.7 and 52.5%; the DR at FPR of 5%
      were 60.0, 49.7 and 37.6%, respectively. CONCLUSIONS: Performance of screening
      for PE by MAP is best when measurements are taken at both 11-13 and 20-24 weeks'
      gestation than at only one of these gestational ranges.

PMID- 24752038
TI  - A strategy to create spin-split metallic bands on silicon using a dense alloy
      layer.
AB  - To exploit Rashba effect in a 2D electron gas on silicon surface for spin
      transport, it is necessary to have surface reconstruction with spin-split
      metallic surface-state bands. However, metals with strong spin-orbit coupling
      (e.g., Bi, Tl, Sb, Pt) induce reconstructions on silicon with almost exclusively
      spin-split insulating bands. We propose a strategy to create spin-split metallic
      bands using a dense 2D alloy layer containing a metal with strong spin-orbit
      coupling and another metal to modify the surface reconstruction. Here we report
      two examples, i.e., alloying reconstruction with Na and Tl/Si(111)1 * 1
      reconstruction with Pb. The strategy provides a new paradigm for creating
      metallic surface state bands with various spin textures on silicon and therefore
      enhances the possibility to integrate fascinating and promising capabilities of
      spintronics with current semiconductor technology. 

PMID- 24752040
TI  - Suv39h1 protects from myocardial ischemia-reperfusion injury in diabetic rats.
AB  - BACKGROUND: Patients with diabetes are at increased risk of ischemic events.
      Suv39h1 is a histone methyltransferase that catalyzes the methylation of histone
      3 lysine 9, which is associated with the suppression of inflammatory genes in
      diabetes. However, the role of Suv39h1 in myocardial ischemia/reperfusion (I/R)
      injury under diabetic condition has not been evaluated. METHODS: To generate
      diabetic model, male SD rats were fed with 60% fat diet followed by
      intraperitoneal injection with 40mg/kg streptozotocin. Adenovirus encoding
      Suv39h1 gene was used for Suv39h1 overexpression. Each rat received injections of
      adenovirus at five myocardial sites. Three days after gene transfection, each rat
      was subjected to left main coronary artery occlusion and reperfusion. After 30
      min ischemia and reperfusion for 4 h, the rats were euthanized for real-time PCR,
      Western blot, immunohistochemical staining, and morphometric analysis. RESULTS:
      Delivery of Ad-Suv39h1 into the hearts of diabetic rats could markedly increase
      Suv39h1 expression. Up-regulation of Suv39h1 significantly reduced infarct size
      and tissue damage after I/R injury, which was associated with protection from
      apoptosis of cardiac myocytes and reduction of inflammatory response. In
      addition, compared with injury group, Ad-Suv39h1 led to a decreased activity of
      mitogen-activated protein kinase family and its down-steam transcriptional factor
      NF-kappaB. CONCLUSION: Overexpression of Suv39h1 results in the de-activation of
      proinflammatory pathways and reduced apoptosis and myocardial injury. Therefore,
      Suv39h1 might represent a novel therapeutic strategy to reduce I/R injury under
      diabetic condition.

PMID- 24752041
TI  - Effectiveness assessment of soil conservation measures in reducing soil erosion
      in Baiquan County of Northeastern China by using (137)Cs techniques.
AB  - Accelerated soil erosion is considered as a major land degradation process
      resulting in increased sediment production and sediment-associated nutrient
      inputs to the rivers. Over the last decade, several soil conservation programs
      for erosion control have been conducted throughout Northeastern China. Reliable
      information on soil erosion rates is an essential prerequisite to assess the
      effectiveness of soil conservation measures. A study was carried out in Baiquan
      County of Northeastern China to assess the effectiveness of soil conservation
      measures in reducing soil erosion using the (137)Cs tracer technique and related
      techniques. This study reports the use of (137)Cs measurements to quantify medium
      term soil erosion rates in traditional slope farmland, contour cropping farmland
      and terrace farmland in the Dingjiagou catchment and the Xingsheng catchment of
      Baiquan County. The (137)Cs reference inventory of 2532 +/- 670 Bq m(-2) was
      determined. Based on the principle of the (137)Cs tracer technique, soil erosion
      rates were estimated. The results showed that severe erosion on traditional slope
      farmland is the dominant soil erosion process in the area. The terrace measure
      reduced soil erosion rates by 16% for the entire slope. Typical net soil erosion
      rates are estimated to be 28.97 Mg per hectare per year for traditional slope
      farmland and 25.04 Mg per hectare per year for terrace farmland in the Dingjiagou
      catchment. In contrast to traditional slope farmland with a soil erosion rate of
      34.65 Mg per hectare per year, contour cultivation reduced the soil erosion rate
      by 53% resulting in a soil erosion rate of 22.58 Mg per hectare per year in the
      Xingsheng catchment. These results indicated that soil losses can be controlled
      by changing tillage practices from the traditional slope farmland cultivation to
      the terrace or contour cultivation. 

PMID- 24752039
TI  - Energy recovery in individuals with knee osteoarthritis.
AB  - OBJECTIVE: Pathological gaits have been shown to limit transfer between potential
      (PE) and kinetic (KE) energy during walking, which can increase locomotor costs.
      The purpose of this study was to examine whether energy exchange would be limited
      in people with knee osteoarthritis (OA). METHODS: Ground reaction forces during
      walking were collected from 93 subjects with symptomatic knee OA (self-selected
      and fast speeds) and 13 healthy controls (self-selected speed) and used to
      calculate their center of mass (COM) movements, PE and KE relationships, and
      energy recovery during a stride. Correlations and linear regressions examined the
      impact of energy fluctuation phase and amplitude, walking velocity, body mass,
      self-reported pain, and radiographic severity on recovery. Paired t-tests were
      run to compare energy recovery between cohorts. RESULTS: Symptomatic knee OA
      subjects displayed lower energetic recovery during self-selected walking speeds
      than healthy controls (P = 0.0018). PE and KE phase relationships explained the
      majority (66%) of variance in recovery. Recovery had a complex relationship with
      velocity and its change across speeds was significantly influenced by the self
      selected walking speed of each subject. Neither radiographic OA scores nor
      subject self-reported measures demonstrated any relationship with energy
      recovery. CONCLUSIONS: Knee OA reduces effective exchange of PE and KE,
      potentially increasing the muscular work required to control movements of the
      COM. Gait retraining may return subjects to more normal patterns of energy
      exchange and allow them to reduce fatigue.

PMID- 24752042
TI  - Population growth of the Cladoceran, Daphnia magna: a quantitative analysis of
      the effects of different algal food.
AB  - In this study, we examined the effects of two phytoplankton species, Chlorella
      vulgaris and Stephanodiscus hantzschii, on growth of the zooplankton Daphnia
      magna. Our experimental approach utilized stable isotopes to determine the
      contribution of food algae to offspring characteristics and to the size of adult
      D. magna individuals. When equal amounts of food algae were provided (in terms of
      carbon content), the size of individuals, adult zooplankton, and their offspring
      increased significantly following the provision of S. hantzschii, but not after
      the provision of C. vulgaris or of a combination of the two species. Offspring
      size was unaffected when C. vulgaris or a mixture of the two algal species was
      delivered, whereas providing only S. hantzschii increased the production of
      larger-sized offspring. Stable isotope analysis revealed significant assimilation
      of diatom-derived materials that was important for the growth of D. magna
      populations. Our results confirm the applicability of stable isotope approaches
      for clarifying the contribution of different food algae and elucidate the
      importance of food quality for growth of D. magna individuals and populations.
      Furthermore, we expect that stable isotope analysis will help to further
      precisely examine the contribution of prey to predators or grazers in controlled
      experiments. 

PMID- 24752043
TI  - Cardiovascular comorbidities in childhood psoriasis.
AB  - BACKGROUND: Psoriasis is a common, chronic, systemic inflammatory skin disease
      associated with numerous cardiovascular comorbidities. Much evidence of this
      association exists in the adult population, data available in childhood psoriasis
      is more limited. OBJECTIVES: To analyze the prevalence of excess adiposity,
      cardiovascular risk factors, metabolic syndrome and lipid profile in children
      with psoriasis comparing to control group with similar age and sex distribution.
      MATERIALS & METHODS: A case-control study was conducted with children, 5-15 years
      old, with moderate-to-severe plaque-type psoriasis and a control group comprising
      children with other skin diseases without systemic inflammatory diseases.
      RESULTS: Psoriatic children had a significantly higher prevalence and greater
      odds of excess adiposity compared to controls: BMI (>=85(th) percentile; OR 4.4;
      95%CI 1.2-15.6), waist circumference (>75(th) percentile; OR 7.4; 95%CI 2.0-27.7)
      and waist-to-height ratio (>0.490; OR 4.6; 95%CI 1.3-17.0). A higher prevalence
      of metabolic syndrome was observed in children with psoriasis compared to
      controls (25% vs 3.7%; P = 0.07), and two components of the metabolic syndrome
      were significantly higher in the psoriasis group: waist circumference (75% vs
      29.6%; P = 0.002) and the high blood pressure component (30% vs 3.7% P = 0.032).
      Finally, an altered and more atherogenic lipid profile was observed among
      psoriatic patients without excess adiposity. CONCLUSION: This study demonstrates
      that comorbidities known to be associated with adult psoriasis are also observed
      in childhood psoriasis, reinforcing the need for screening cardiovascular
      comorbidities in children with psoriasis and promoting healthy lifestyle choices
      in these patients. Moreover, it also suggests that its association with psoriasis
      may be in part genetically determined rather than uniquely acquired.

PMID- 24752045
TI  - Prognostic impact of [18F]fluorodeoxyglucose positron emission tomography
      scanning in the era of molecular oncology.

PMID- 24752046
TI  - Progress against GI cancer during the American Society of Clinical Oncology's
      first 50 years.

PMID- 24752044
TI  - Breast cancer after chest radiation therapy for childhood cancer.
AB  - PURPOSE: The risk of breast cancer is high in women treated for a childhood
      cancer with chest irradiation. We sought to examine variations in risk resulting
      from irradiation field and radiation dose. PATIENTS AND METHODS: We evaluated
      cumulative breast cancer risk in 1,230 female childhood cancer survivors treated
      with chest irradiation who were participants in the CCSS (Childhood Cancer
      Survivor Study). RESULTS: Childhood cancer survivors treated with lower delivered
      doses of radiation (median, 14 Gy; range, 2 to 20 Gy) to a large volume (whole
      lung field) had a high risk of breast cancer (standardized incidence ratio [SIR],
      43.6; 95% CI, 27.2 to 70.3), as did survivors treated with high doses of
      delivered radiation (median, 40 Gy) to the mantle field (SIR, 24.2; 95% CI, 20.7
      to 28.3). The cumulative incidence of breast cancer by age 50 years was 30% (95%
      CI, 25 to 34), with a 35% incidence among Hodgkin lymphoma survivors (95% CI, 29
      to 40). Breast cancer-specific mortality at 5 and 10 years was 12% (95% CI, 8 to
      18) and 19% (95% CI, 13 to 25), respectively. CONCLUSION: Among women treated for
      childhood cancer with chest radiation therapy, those treated with whole-lung
      irradiation have a greater risk of breast cancer than previously recognized,
      demonstrating the importance of radiation volume. Importantly, mortality
      associated with breast cancer after childhood cancer is substantial.

PMID- 24752048
TI  - Intraluminal Superior Vena Cava Metastasis in a Patient With Poorly
      Differentiated Thyroid Carcinoma.

PMID- 24752047
TI  - Treatment of high-risk Philadelphia chromosome-negative acute lymphoblastic
      leukemia in adolescents and adults according to early cytologic response and
      minimal residual disease after consolidation assessed by flow cytometry: final
      results of the PETHEMA ALL-AR-03 trial.
AB  - PURPOSE: Minimal residual disease (MRD) is an important prognostic factor in
      adults with acute lymphoblastic leukemia (ALL) and may be used for treatment
      decisions. The Programa Espanol de Tratamientos en Hematologia (PETHEMA) ALL-AR
      03 trial (Treatment of High Risk Adult Acute Lymphoblastic Leukemia [LAL
      AR/2003]) assigned adolescent and adult patients (age 15 to 60 years) with high
      risk ALL (HR-ALL) without the Philadelphia (Ph) chromosome to chemotherapy or to
      allogeneic hematopoietic stem-cell transplantation (allo-HSCT) according to early
      cytologic response (day 14) and flow-MRD level after consolidation. PATIENTS AND
      METHODS: Patients with good early cytologic response (< 10% blasts in bone marrow
      at day 14 of induction) and a flow-MRD level less than 5 * 10(-4) at the end of
      consolidation were assigned to delayed consolidation and maintenance therapy, and
      allo-HSCT was scheduled in patients with poor early cytologic response or flow
      MRD level >= 5 * 10(-4). RESULTS: Complete remission was attained in 282 (87%) of
      326 patients, and 179 (76%) of 236 patients who completed early consolidation
      were assigned by intention-to treat to receive allo-HSCT (71) or chemotherapy
      (108). Five-year disease-free survival (DFS) and overall survival (OS)
      probabilities were 37% and 35% for the whole series, 32% and 37% for patients
      assigned to allo-HSCT, and 55% and 59% for those assigned to chemotherapy.
      Multivariable analysis showed poor MRD clearance (>= 1 * 10(-3) after induction
      and >= 5 * 10(-4) after early consolidation) as the only prognostic factor for
      DFS and OS. CONCLUSION: Prognosis for Ph-negative HR-ALL in adolescents and
      adults with good early response to induction and low flow-MRD levels after
      consolidation is quite favorable when allo-HSCT is avoided. In this study, the
      pattern of MRD clearance was the only prognostic factor for DFS and OS.

PMID- 24752049
TI  - Reference pricing with evidence development: a way forward for proton therapy.

PMID- 24752050
TI  - Reply to J.-S. Ryu et al and A.T. Berman et al.

PMID- 24752051
TI  - Lessons learned from Radiation Therapy Oncology Group 0525 trial.

PMID- 24752052
TI  - Predicting survival in non-small-cell lung cancer using positron emission
      tomography: several conclusions from multiple comparisons.

PMID- 24752053
TI  - EGFR-Driven Behavior and Intrapatient T790M Mutation Heterogeneity of Non-Small
      Cell Carcinoma With Squamous Histology.

PMID- 24752054
TI  - Adult Onset Primary Pineal Rhabdomyosarcoma.

PMID- 24752055
TI  - Tumor regression grading in rectal cancer: is it time to move forward?

PMID- 24752056
TI  - Tumor regression grading after preoperative chemoradiotherapy for locally
      advanced rectal carcinoma revisited: updated results of the CAO/ARO/AIO-94 trial.
AB  - PURPOSE: We previously described the prognostic impact of tumor regression
      grading (TRG) on the outcome of patients with rectal carcinoma treated with
      preoperative chemoradiotherapy (CRT) in the CAO/ARO/AIO-94 trial. Here we report
      long-term results after a median follow-up of 132 months. PATIENTS AND METHODS:
      TRG after preoperative CRT was determined in 386 surgical specimens by the amount
      of viable tumor cells versus fibrosis, ranging from TRG 4 (no viable tumor cells)
      to TRG 0 (no signs of regression). Clinicopathologic parameters and TRG were
      correlated to the cumulative incidence of local recurrence, distant metastasis,
      and disease-free survival (DFS). RESULTS: Ten-year cumulative incidence of
      distant metastasis and DFS were 10.5% and 89.5% for patients with TRG 4 (complete
      regression), 29.3% and 73.6% for TRG 2 and 3 (intermediate regression), and 39.6%
      and 63% for TRG 0 and 1 (poor regression), respectively (P = .005 and P = .008,
      respectively). On multivariable analysis, residual lymph node metastasis (ypN+)
      and TRG were the only independent prognostic factors for cumulative incidence of
      distant metastasis (P < .001 and P = .035, respectively) and DFS (P < .001 and P
      = .039, respectively), whereas local recurrence was significantly affected by ypN
      status (P < .001) and lymphatic invasion (P = .026). CONCLUSION: Complete and
      intermediate tumor regressions were associated with improved long-term outcome in
      patients with rectal carcinoma after preoperative CRT independent of
      clinicopathologic parameters. This classification system needs to be
      prospectively tested in multiple data sets to validate its reproducibility in a
      wider setting.

PMID- 24752058
TI  - Intralesional Methotrexate for Treatment of Invasive Squamous Cell Carcinomas in
      a Patient Taking Vemurafenib for Treatment of Metastatic Melanoma.

PMID- 24752057
TI  - Provision and discussion of survivorship care plans among cancer survivors:
      results of a nationally representative survey of oncologists and primary care
      physicians.
AB  - PURPOSE: Survivorship care planning should involve discussions between providers
      and cancer survivors to address survivors' needs and optimize adherence. We
      examined the frequency and factors associated with oncologists' and primary care
      physicians' (PCPs) reports of provision of written survivorship care plans (SCPs)
      and discussion of survivorship care recommendations with survivors. METHODS: A
      nationally representative sample of 1,130 oncologists and 1,020 PCPs was surveyed
      about survivorship care practices with survivors. Logistic regression models
      predicted multilevel factors associated with providing SCPs or discussing
      recommendations with survivors. RESULTS: Although a majority of oncologists (64%)
      reported always/almost always discussing survivorship care recommendations with
      survivors, fewer also discussed who survivors should see for cancer-related and
      other follow-up care (32%); fewer still also provided a written SCP to the
      survivor (< 5%). Survivorship care recommendations and provider responsibility
      were not regularly discussed by PCPs and survivors (12%). Oncologists who
      reported detailed training about late and long-term effects of cancer were more
      likely to provide written SCPs (odds ratio [OR], 1.73; 95% CI, 1.22 to 2.44) and
      discuss survivorship care planning with survivors (OR, 2.02; 95% CI, 1.51 to
      2.70). PCPs who received SCPs from oncologists were 9* more likely (95% CI, 5.74
      to 14.82) to report survivorship discussions with survivors. CONCLUSION: A
      minority of both PCPs and oncologists reported consistently discussing and
      providing SCPs to cancer survivors. Training and knowledge specific to
      survivorship care and coordinated care between PCPs and oncologists were
      associated with increased survivorship discussions with survivors. These
      nationally representative data provide a useful benchmark to assess
      implementation of new efforts to improve the follow-up care of survivors.

PMID- 24752059
TI  - Molecular Response of e19a2 BCR-ABL1 Chronic Myeloid Leukemia With Double
      Philadelphia Chromosome to Dasatinib.

PMID- 24752060
TI  - Reply to M.C. Chamberlain.

PMID- 24752062
TI  - Biliary complications after orthotopic liver transplantation.
AB  - PURPOSE OF REVIEW: The incidence, pathogenesis and management of the most common
      biliary complications are summarized, with an emphasis on nonanastomotic biliary
      strictures (NAS) and potential strategies to prevent NAS after liver
      transplantation. RECENT FINDINGS: NAS have variable presentations in time and
      localization, suggesting various underlying pathogeneses. Early-onset NAS
      (presentation within 1 year) have shown to be largely related to ischemia-induced
      bile duct injury, whereas late-onset NAS [>1 year after orthotopic liver
      transplantation (OLT)] have more immune-mediated causes. Cytotoxic hydrophobic
      bile salts and impaired biliary HCO3 secretion may also play a role in the
      occurrence of NAS. Recently, insufficient biliary epithelial regeneration
      capacity after transplantation has also been suggested to play a major role in
      the pathogenesis of NAS. A potential strategy to prevent NAS has been proposed to
      be preservation by machine perfusion instead of classical static cold storage.
      Although machine perfusion has been shown to be a better preservation method for
      the liver parenchyma, efficacy in preventing ischemic injury of the biliary
      epithelium is largely unknown. SUMMARY: The potential advantages of machine
      perfusion are very promising as it may provide better protection of the
      vulnerable bile ducts against ischemia-reperfusion injury. Clinical trials will
      be needed to demonstrate the impact of machine perfusion in reducing the
      incidence of biliary complications, especially NAS, after OLT.

PMID- 24752061
TI  - Cognition and hippocampal plasticity in the mouse is altered by monosomy of a
      genomic region implicated in Down syndrome.
AB  - Down syndrome (DS) is due to increased copy number of human chromosome 21. The
      contribution of different genetic regions has been tested using mouse models. As
      shown previously, the Abcg1-U2af1 genetic region contributes to cognitive defects
      in working and short-term recognition memory in Down syndrome mouse models. Here
      we analyzed the impact of monosomy of the same genetic interval, using a new
      mouse model, named Ms2Yah. We used several cognitive paradigms and did not detect
      defects in the object recognition or the Morris water maze tests. However,
      surprisingly, Ms2Yah mice displayed increased associative memory in a pure
      contextual fear-conditioning test and decreased social novelty interaction along
      with a larger long-term potentiation recorded in the CA1 area following
      stimulation of Schaffer collaterals. Whole-genome expression studies carried out
      on hippocampus showed that the transcription of only a small number of genes is
      affected, mainly from the genetic interval (Cbs, Rsph1, Wdr4), with a few
      additional ones, including the postsynaptic Gabrr2, Gabbr1, Grid2p, Park2, and
      Dlg1 and the components of the Ubiquitin-mediated proteolysis (Anapc1, Rnf7,
      Huwe1, Park2). The Abcg1-U2af1 region is undeniably encompassing dosage-sensitive
      genes or elements whose change in copy number directly affects learning and
      memory, synaptic function, and autistic related behavior. 

PMID- 24752063
TI  - Formation and regeneration of the urothelium.
AB  - PURPOSE OF REVIEW: This review addresses significant changes in our understanding
      of urothelial development and regeneration. Understanding urothelial
      differentiation will be important in the push to find new methods of bladder
      reconstruction and augmentation, as well as identification of bladder cancer stem
      cells. RECENT FINDINGS: This review will cover recent findings including the
      identification of novel progenitor cells in the embryo and adult urothelium,
      function of the urothelium, and regeneration of the urothelium. Using Cre-lox
      recombination with cell-type-specific Cre lines, lineage studies from our
      laboratory have revealed novel urothelial cell types and progenitors that are
      critical for formation and regeneration of the urothelium. Interestingly, our
      studies indicate that Keratin-5-expressing basal cells, which have previously
      been proposed to be urothelial stem cells, are a self-renewing unipotent
      population, whereas P-cells, a novel urothelial cell type, are progenitors in the
      embryo, and intermediate cells serve as a progenitor pool in the adult. SUMMARY:
      These findings could have important implications for our understanding of cancer
      tumorigenesis and could move the fields of regeneration and reconstruction
      forward.

PMID- 24752064
TI  - Bacterial biliary tract infections in liver transplant recipients.
AB  - PURPOSE OF REVIEW: The purpose of this study is to provide an overview of
      bacterial biliary tract infections in liver transplant recipients with a focus on
      pathogenesis and conservative treatment strategies. RECENT FINDINGS: The
      development of interventional endoscopic and radiologic interventions has
      improved the outcome of conservative treatments for bile tract strictures and
      bilomas. However, recent data show an important rise of infections with multidrug
      resistant (MDR) pathogens in liver transplant recipients. SUMMARY: Both recurrent
      cholangitis and infected bilomas are bacterial biliary tract infections in liver
      transplant recipients responsible for significant morbidity and graft loss, which
      require a multidisciplinary approach. Risk factors for biliary tract strictures
      and bilomas formation have recently been identified. With the improved outcome of
      a conservative management including prolonged and/or recurrent antibiotic
      treatments, the risk of selecting resistant pathogens is increased. There is an
      urgent need to develop new strategies to reduce the risk of secondary infections
      by MDR isolates in liver transplant recipients.

PMID- 24752066
TI  - Solid organ transplant pathology: updates for a complex specialty.

PMID- 24752065
TI  - Chronic mucosal inflammation/inflammatory bowel disease-like inflammation after
      intestinal transplantation: where are we now?
AB  - PURPOSE OF REVIEW: The purpose of this review is to highlight the similarities
      between inflammatory bowel disease and the state of the intestine allograft after
      transplantation. RECENT FINDINGS: The mutant nucleotide-binding oligomerization
      protein 2 (NOD2) gene, which encodes for an intracellular protein that serves as
      an innate immune system microbial sensor in macrophages, dendritic cells, and
      certain intestinal epithelial cells, has been recognized as a risk factor in
      Crohn's disease. Similarly, recent studies have also highlighted the contribution
      the NOD2 mutation may have on intestinal failure itself. More specifically, in
      intestinal transplant recipients with the NOD2 mutation, the discovery of the
      reduced ability to prevent bacterial clearance, increased enterocyte stress
      response, and failure of key downstream expression of important cytokines and
      growth factors have been implicated as major factors in intestinal transplant
      outcomes, namely graft loss and septic death. Treatment strategies with anti
      tumor necrosis factor (TNF) alpha, similar to inflammatory bowel disease, have
      been employed in intestinal transplantation with promising results. SUMMARY: In
      intestinal transplantation, there is evidence that the classical alloimmunity
      pathways that lead toward graft dysfunction and eventual graft loss may, in fact,
      be working in concert with a disordered innate immune system to produce a state
      of chronic inflammation not unlike that seen in inflammatory bowel disease.

PMID- 24752067
TI  - Update on surgical therapies for intestinal failure.
AB  - PURPOSE OF REVIEW: Parenteral nutrition enables long-term survival in patients
      with intestinal failure; however, it is associated with life-threatening
      complications necessitating alternative techniques of management to enable
      weaning parenteral nutrition and minimizing parenteral nutrition-associated
      comorbidities. This review aims at discussing the indications and techniques most
      commonly utilized for surgical management in a short gut. RECENT FINDINGS:
      Surgical therapy for short gut has evolved and undergone refinement in the past
      30-40  years with the older procedures being largely abandoned and replaced by
      newer and refined techniques. Lengthening surgeries (longitudinal intestinal
      lengthening and tapering and serial transverse enteroplasty) are the most
      commonly applied procedures in a dilated bowel with intestinal transplantation
      option reserved as a last resort for recurrent life-threatening central venous
      line infections, progressive loss of central venous access, and development of
      progressive liver disease. SUMMARY: Management of intestinal failure requires a
      multidisciplinary approach to optimize intestinal rehabilitation and overall
      patient outcome. Although intestinal transplantation remains an excellent option
      for patients with severe life-threatening complications, autologous intestinal
      reconstruction appears to remain the better overall option.

PMID- 24752068
TI  - Structure-based discovery of a small non-peptidic Neuropilins antagonist exerting
      in vitro and in vivo anti-tumor activity on breast cancer model.
AB  - Neuropilin-1/-2 (+33 NRPs), VEGF-A165 co-receptors, are over-expressed during
      cancer progression. Thus, NRPs targeted drug development is challenged using a
      multistep in silico/in vitro screening procedure. The first fully non-peptidic
      VEGF-A165/NRPs protein-protein interaction antagonist (IC50=34 MUM) without
      effect on pro-angiogenic kinases has been identified (compound-1). This hit
      showed breast cancer cells anti-proliferative activity (IC50=0.60 MUM). Compound
      1 treated NOG-xenografted mice significantly exerted tumor growth inhibition,
      which is correlated with Ki-67(low) expression and apoptosis. Furthermore,
      CD31(+)/CD34(+) vessels are reduced in accordance with HUVEC-tube formation
      inhibition (IC50=0.20 MUM). Taking together, compound-1 is the first fully
      organic inhibitor targeting NRPs.

PMID- 24752069
TI  - Insect attraction versus plant defense: young leaves high in glucosinolates
      stimulate oviposition by a specialist herbivore despite poor larval survival due
      to high saponin content.
AB  - Glucosinolates are plant secondary metabolites used in plant defense. For insects
      specialized on Brassicaceae, such as the diamondback moth, Plutella xylostella L.
      (Lepidoptera: Plutellidae), glucosinolates act as "fingerprints" that are
      essential in host plant recognition. Some plants in the genus Barbarea
      (Brassicaceae) contain, besides glucosinolates, saponins that act as feeding
      deterrents for P. xylostella larvae, preventing their survival on the plant. Two
      choice oviposition tests were conducted to study the preference of P. xylostella
      among Barbarea leaves of different size within the same plant. P. xylostella laid
      more eggs per leaf area on younger leaves compared to older ones. Higher
      concentrations of glucosinolates and saponins were found in younger leaves than
      in older ones. In 4-week-old plants, saponins were present in true leaves, while
      cotyledons contained little or no saponins. When analyzing the whole foliage of
      the plant, the content of glucosinolates and saponins also varied significantly
      in comparisons among plants that were 4, 8, and 12 weeks old. In Barbarea plants
      and leaves of different ages, there was a positive correlation between
      glucosinolate and saponin levels. This research shows that, in Barbarea plants,
      ontogenetical changes in glucosinolate and saponin content affect both attraction
      and resistance to P. xylostella. Co-occurrence of a high content of
      glucosinolates and saponins in the Barbarea leaves that are most valuable for the
      plant, but are also the most attractive to P. xylostella, provides protection
      against this specialist herbivore, which oviposition behavior on Barbarea seems
      to be an evolutionary mistake. 

PMID- 24752070
TI  - Viral infection is not uncommon in adult patients with severe hospital-acquired
      pneumonia.
AB  - BACKGROUND: Viral pathogens have not generally been regarded as important causes
      of severe hospital-acquired pneumonia (HAP), except in patients with hematologic
      malignancy or transplant recipients. We investigated the role and distribution of
      viruses in adult with severe HAP who required intensive care. METHODS: From March
      2010 to February 2012, adult patients with severe HAP required admission to the
      intensive care unit (ICU), 28-bed medical ICU in a tertiary care hospital, were
      prospectively enrolled. Respiratory viruses were detected using multiplex reverse
      transcription polymerase chain reaction and/or shell vial culture. RESULTS: A
      total of 262 patients were enrolled and 107 patients (40.8%) underwent
      bronchoscopic BAL for etiologic diagnosis. One hundred and fifty-six patients
      (59.5%) had bacterial infections and 59 patients (22.5%) had viral infections.
      Viruses were detected in BAL fluid specimens of 37 patients (62.7%, 37/59). The
      most commonly identified viruses were respiratory syncytial virus and
      parainfluenza virus (both 27.1%, 16/59), followed by rhinovirus (25.4%, 15/59),
      and influenza virus (16.9%, 10/59). Twenty-one patients (8.0%, 21/262) had
      bacterial-viral coinfections and Staphylococcus aureus was the most commonly
      coexisting bacteria (n = 10). Viral infection in non-immunocompromised patients
      was not uncommon (11.1%, 16/143), although it was not as frequent as that in
      immunocompromised patients (36.4%, 43/119). Non-immunocompromised patients were
      significantly older than immunocompromised patients and had significantly higher
      rates of underlying chronic obstructive pulmonary disease, tuberculous destroyed
      lung and chronic kidney disease. The 28 day mortalities of patients with
      bacterial infections, viral infections and bacterial-viral coinfections were not
      significantly different (29.5%, 35.6% and 19.0%, respectively; p = 0.321).
      CONCLUSIONS: Viral pathogens are not uncommon in adult patients with severe HAP
      who required ICU admission. Since viral pathogens may cause severe HAP and could
      be a potential source of viral transmission, further investigation is required to
      delineate the role of viral pathogens in severe HAP.

PMID- 24752074
TI  - Long-term follow-up of a novel anastomotic device in a canine model.
AB  - Construction of intestinal anastomosis is a fundamental general surgery skill.
      New constraints in creating safe, effective anastomoses are faced, however, even
      as minimally invasive surgery techniques continue to gain popular and scientific
      support. We present our experience in developing and testing a novel anastomotic
      device (AD) constructed of a shape memory metal, with long-term follow-up in a
      canine model. This device has the potential for both laparoscopic and endoscopic
      delivery because of its unique design and adaptable deployment system. Eight
      canines had gastroduodenal and jejunojejunal anastomoses formed with the AD: the
      gastroduodenal anastomosis by transecting the stomach immediately distal to the
      pylorus and forming a side-to-side functional end-to-end anastomosis and the
      jejunojejunal anastomosis similarly following transection in the mid-jejunum.
      Four animals were survived for 6 months, and 4 for 12 months. At the study's end,
      the animals were euthanized and the anastomotic sites harvested for both gross
      and microscopic pathology. Two animals developed postoperative complications: one
      a mechanical bowel obstruction from bedding ingestion that required laparotomy,
      and one an ileus that conservative management resolved. All animals survived to
      their endpoints, displaying normal growth and development. All jejunojejunal
      anastomoses had AD passage and microscopic evidence of complete healing.
      Meanwhile, none of the gastroduodenal devices passed, with microscopy
      demonstrating incomplete mucosalization. This AD is highly effective in forming
      jejunojejunal anastomoses. Gastroduodenal anastomoses, while highly functional,
      retained the device without complete healing. Future studies using a more human
      like animal model and an anastomotic technique avoiding the thick pylorus muscle
      should yield better results. 

PMID- 24752071
TI  - Are you gonna leave me? Separation anxiety is associated with increased amygdala
      responsiveness and volume.
AB  - The core feature of separation anxiety is excessive distress when faced with
      actual or perceived separation from people to whom the individual has a strong
      emotional attachment. So far little is known about the neurobiological
      underpinnings of separation anxiety. Therefore, we investigated functional
      (amygdala responsiveness and functional connectivity during threat-related
      emotion processing) and structural (grey matter volume) imaging markers
      associated with separation anxiety as measured with the Relationship Scale
      Questionnaire in a large sample of healthy adults from the Munster Neuroimaging
      Cohort (N = 320). We used a robust emotional face-matching task and acquired high
      resolution structural images for morphometric analyses using voxel-based
      morphometry. The main results were positive associations of separation anxiety
      scores with amygdala reactivity to emotional faces as well as increased amygdala
      grey matter volumes. A functional connectivity analysis revealed positive
      associations between separation anxiety and functional coupling of the amygdala
      with areas involved in visual processes and attention, including several
      occipital and somatosensory areas. Taken together, the results suggest a higher
      emotional involvement in subjects with separation anxiety while watching negative
      facial expressions, and potentially secondary neuro-structural adaptive
      processes. These results could help to understand and treat (adult) separation
      anxiety. 

PMID- 24752075
TI  - Molecular characterization and expression of a novel alcohol oxidase from
      Aspergillus terreus MTCC6324.
AB  - The alcohol oxidase (AOx) cDNA from Aspergillus terreus MTCC6324 with an open
      reading frame (ORF) of 2001 bp was constructed from n-hexadecane induced cells
      and expressed in Escherichia coli with a yield of ~4.2 mg protein g-1 wet cell.
      The deduced amino acid sequences of recombinant rAOx showed maximum structural
      homology with the chain B of aryl AOx from Pleurotus eryngii. A functionally
      active AOx was achieved by incubating the apo-AOx with flavin adenine
      dinucleotide (FAD) for ~80 h at 16 degrees C and pH 9.0. The isoelectric point
      and mass of the apo-AOx were found to be 6.5+/-0.1 and ~74 kDa, respectively.
      Circular dichroism data of the rAOx confirmed its ordered structure. Docking
      studies with an ab-initio protein model demonstrated the presence of a conserved
      FAD binding domain with an active substrate binding site. The rAOx was specific
      for aryl alcohols and the order of its substrate preference was 4-methoxybenzyl
      alcohol >3-methoxybenzyl alcohol>3, 4-dimethoxybenzyl alcohol > benzyl alcohol. A
      significantly high aggregation to ~1000 nm (diameter) and catalytic efficiency
      (kcat/Km) of 7829.5 min-1 mM-1 for 4-methoxybenzyl alcohol was also demonstrated
      for rAOx. The results infer the novelty of the AOx and its potential biocatalytic
      application. 

PMID- 24752076
TI  - Discovery of prognostic biomarker candidates of lacunar infarction by
      quantitative proteomics of microvesicles enriched plasma.
AB  - BACKGROUND: Lacunar infarction (LACI) is a subtype of acute ischemic stroke
      affecting around 25% of all ischemic stroke cases. Despite having an excellent
      recovery during acute phase, certain LACI patients have poor mid- to long-term
      prognosis due to the recurrence of vascular events or a decline in cognitive
      functions. Hence, blood-based biomarkers could be complementary prognostic and
      research tools. METHODS AND FINDING: Plasma was collected from forty five
      patients following a non-disabling LACI along with seventeen matched control
      subjects. The LACI patients were monitored prospectively for up to five years for
      the occurrence of adverse outcomes and grouped accordingly (i.e., LACI-no adverse
      outcome, LACI-recurrent vascular event, and LACI-cognitive decline without any
      recurrence of vascular events). Microvesicles-enriched fractions isolated from
      the pooled plasma of four groups were profiled by an iTRAQ-guided discovery
      approach to quantify the differential proteome. The data have been deposited to
      the ProteomeXchange with identifier PXD000748. Bioinformatics analysis and data
      mining revealed up-regulation of brain-specific proteins including myelin basic
      protein, proteins of coagulation cascade (e.g., fibrinogen alpha chain,
      fibrinogen beta chain) and focal adhesion (e.g., integrin alpha-IIb, talin-1, and
      filamin-A) while albumin was down-regulated in both groups of patients with
      adverse outcome. CONCLUSION: This data set may offer important insight into the
      mechanisms of poor prognosis and provide candidate prognostic biomarkers for
      validation on larger cohort of individual LACI patients.

PMID- 24752077
TI  - GlycoDelete engineering of mammalian cells simplifies N-glycosylation of
      recombinant proteins.
AB  - Heterogeneity in the N-glycans on therapeutic proteins causes difficulties for
      protein purification and process reproducibility and can lead to variable
      therapeutic efficacy. This heterogeneity arises from the multistep process of
      mammalian complex-type N-glycan synthesis. Here we report a glycoengineering
      strategy--which we call GlycoDelete--that shortens the Golgi N-glycosylation
      pathway in mammalian cells. This shortening results in the expression of proteins
      with small, sialylated trisaccharide N-glycans and reduced complexity compared to
      native mammalian cell glycoproteins. GlycoDelete engineering does not interfere
      with the functioning of N-glycans in protein folding, and the physiology of cells
      modified by GlycoDelete is similar to that of wild-type cells. A therapeutic
      human IgG expressed in GlycoDelete cells had properties, such as reduced initial
      clearance, that might be beneficial when the therapeutic goal is antigen
      neutralization. This strategy for reducing N-glycan heterogeneity on mammalian
      proteins could lead to more consistent performance of therapeutic proteins and
      modulation of biopharmaceutical functions.

PMID- 24752078
TI  - Whole-exome sequencing of circulating tumor cells provides a window into
      metastatic prostate cancer.
AB  - Comprehensive analyses of cancer genomes promise to inform prognoses and precise
      cancer treatments. A major barrier, however, is inaccessibility of metastatic
      tissue. A potential solution is to characterize circulating tumor cells (CTCs),
      but this requires overcoming the challenges of isolating rare cells and
      sequencing low-input material. Here we report an integrated process to isolate,
      qualify and sequence whole exomes of CTCs with high fidelity using a census-based
      sequencing strategy. Power calculations suggest that mapping of >99.995% of the
      standard exome is possible in CTCs. We validated our process in two patients with
      prostate cancer, including one for whom we sequenced CTCs, a lymph node
      metastasis and nine cores of the primary tumor. Fifty-one of 73 CTC mutations
      (70%) were present in matched tissue. Moreover, we identified 10 early trunk and
      56 metastatic trunk mutations in the non-CTC tumor samples and found 90% and 73%
      of these mutations, respectively, in CTC exomes. This study establishes a
      foundation for CTC genomics in the clinic. 

PMID- 24752079
TI  - Genome-wide binding of the CRISPR endonuclease Cas9 in mammalian cells.
AB  - Bacterial type II CRISPR-Cas9 systems have been widely adapted for RNA-guided
      genome editing and transcription regulation in eukaryotic cells, yet their in
      vivo target specificity is poorly understood. Here we mapped genome-wide binding
      sites of a catalytically inactive Cas9 (dCas9) from Streptococcus pyogenes loaded
      with single guide RNAs (sgRNAs) in mouse embryonic stem cells (mESCs). Each of
      the four sgRNAs we tested targets dCas9 to between tens and thousands of genomic
      sites, frequently characterized by a 5-nucleotide seed region in the sgRNA and an
      NGG protospacer adjacent motif (PAM). Chromatin inaccessibility decreases dCas9
      binding to other sites with matching seed sequences; thus 70% of off-target sites
      are associated with genes. Targeted sequencing of 295 dCas9 binding sites in
      mESCs transfected with catalytically active Cas9 identified only one site mutated
      above background levels. We propose a two-state model for Cas9 binding and
      cleavage, in which a seed match triggers binding but extensive pairing with
      target DNA is required for cleavage. 

PMID- 24752080
TI  - Sailfish enables alignment-free isoform quantification from RNA-seq reads using
      lightweight algorithms.
AB  - We introduce Sailfish, a computational method for quantifying the abundance of
      previously annotated RNA isoforms from RNA-seq data. Because Sailfish entirely
      avoids mapping reads, a time-consuming step in all current methods, it provides
      quantification estimates much faster than do existing approaches (typically 20
      times faster) without loss of accuracy. By facilitating frequent reanalysis of
      data and reducing the need to optimize parameters, Sailfish exemplifies the
      potential of lightweight algorithms for efficiently processing sequencing reads. 

PMID- 24752081
TI  - Label-free detection and molecular profiling of exosomes with a nano-plasmonic
      sensor.
AB  - Exosomes show potential for cancer diagnostics because they transport molecular
      contents of the cells from which they originate. Detection and molecular
      profiling of exosomes is technically challenging and often requires extensive
      sample purification and labeling. Here we describe a label-free, high-throughput
      approach for quantitative analysis of exosomes. Our nano-plasmonic exosome
      (nPLEX) assay is based on transmission surface plasmon resonance through periodic
      nanohole arrays. Each array is functionalized with antibodies to enable profiling
      of exosome surface proteins and proteins present in exosome lysates. We show that
      this approach offers improved sensitivity over previous methods, enables portable
      operation when integrated with miniaturized optics and allows retrieval of
      exosomes for further study. Using nPLEX to analyze ascites samples from ovarian
      cancer patients, we find that exosomes derived from ovarian cancer cells can be
      identified by their expression of CD24 and EpCAM, suggesting the potential of
      exosomes for diagnostics. 

PMID- 24752082
TI  - Natural killer cell and T-cell subset distributions and activation influence
      susceptibility to perinatal HIV-1 infection.
AB  - OBJECTIVE: To determine neonatal immunologic factors that correlate with mother
      to-child-transmission of HIV-1. DESIGN: This case-control study compared cord
      blood natural killer (NK) and T-cell populations of HIV-1 exposed infants who
      subsequently acquired infection by 1 month (cases) to those who remained
      uninfected by 1 year of life (controls). Control specimens were selected by
      proportional match on maternal viral load. METHODS: Cryopreserved cord blood
      mononuclear cells (CBMCs) were thawed and stained for multiparameter flow
      cytometry to detect NK and T-cell subsets and activation status. CBMCs were also
      used in a viral suppression assay to evaluate NK cell inhibition of HIV-1
      replication in autologous CD4 T cells. RESULTS: Cord blood from cases contained a
      skewed NK cell repertoire characterized by an increased proportion of CD16CD56 NK
      cells. In addition, cases displayed less-activated CD16CD56 NK cells and CD8 T
      cells, based on HLA-DRCD38 costaining. NK cell suppression of HIV-1 replication
      ex vivo correlated with the proportion of acutely activated CD68CD16CD56 NK
      cells. Finally, we detected a higher proportion of CD27CD45RA effector memory CD4
      and CD8 T cells in cord blood from cases compared with controls. CONCLUSION: When
      controlled for maternal viral load, cord blood from infants who acquired HIV-1
      had a higher proportion of CD16CD56 NK cells, lower NK cell activation and higher
      levels of mature T cells (potential HIV-1 targets) than control infants who
      remained uninfected. Our data provide evidence that infant HIV-1 acquisition may
      be influenced by both innate and adaptive immune cell phenotypes and activation
      status.

PMID- 24752084
TI  - Human umbilical cord-derived mesenchymal stem cells inhibit proliferation but
      maintain survival of Jurkat leukemia cells in vitro by activating Notch
      signaling.
AB  - OBJECTIVE: To investigate the effects of human umbilical cord-derived mesenchymal
      stem cells (hUC-MSCs) on the proliferation and survival of Jurkat leukemia cells
      in vitro and explore the possible mechanism. METHODS: Jurkat leukemia cells were
      co-cultured with hUC-MSCs isolated from human umbilical cord tissues by plastic
      adherence at a ratio of 10:1. The proliferation and survival of the co-cultured
      Jurkat cells, separated by immunomagnetic bead cell sorting on day 4, were
      evaluated by flow cytometry. Western blotting was performed to evaluate the
      activation of Notch signaling in the co-cultured Jurkat cells. RESULTS: Jurkat
      leukemia cells co-cultured with hUC-MSCs for 4 days showed a lowered
      proliferation rate and cell cycle arrest at G0/G1 phase with a reduction in the
      cell apoptotic rate. Notch signaling pathway was activated in the co-cultured
      Jurkat cells as evidenced by an increased cellular expression of HES-1.
      CONCLUSION: Co-culture with hUC-MSCs can inhibit the proliferation of Jurkat
      leukemia cells in vitro and protect the cells from apoptosis by activating Notch
      signaling, indicating a potential shielding effect of MSCs on leukemia cells.

PMID- 24752085
TI  - Clinical outcomes of bridging therapy with fondaparinux versus low-molecular
      weight heparin in patients undergoing atrial fibrillation ablation.
AB  - OBJECTIVE: To compare the efficacy and safety of bridging therapy with
      fondaparinux versus low-molecular-weight heparin (LMWH) in patients undergoing
      radiofrequency ablation for atrial fibrillation (AF). METHODS: AF patients
      undergoing radiofrequency ablation between January, 2009 and June, 2013 in
      Nanfang Hospital were analyzed. The patients received subcutaneous injection of
      either fondaparinux or LMWH as a bridging therapy during warfarin discontinuation
      5 days before the ablation until a post-ablation international normalized ratio
      (INR) of 2.0-3.0 was achieved. Anticoagulant-related complications, identified
      and classified as thromboembolic and bleeding events, were compared between the
      two groups. RESULTS: A total of 465 patients (68% male; mean age 52.3?15 years,
      range 25 to 80 years) were enrolled in the study, including 265 in fondaparinux
      group and 200 in LMWH group. Anticoagulation-related complications were observed
      in 3 patients in fondaparinux group, as compared with 13 in LMWH group (P=0.002),
      but the thromboembolic rate did not differ significantly between the two groups
      (P=0.111). Two patients in fondaparinux group and 8 in LMWH group showed bleeding
      complications (P=0.039). No cardiovascular death occurred in these patients
      during a mean follow-up period of 3 months. CONCLUSIONS: Fondaparinux as the
      bridging therapy during catheter ablation for AF does not increase the risk of
      thromboembolic complications but slightly reduces the risk of bleeding compared
      to LMWH, suggesting its safety and effectiveness for periprocedural
      anticoagulation management in AF patients undergoing radiofrequency ablation.

PMID- 24752083
TI  - Cerebrospinal fluid metabolomics reveals altered waste clearance and accelerated
      aging in HIV patients with neurocognitive impairment.
AB  - OBJECTIVE(S): HIV-associated neurocognitive disorders (HAND) remain prevalent in
      HIV-infected patients on antiretroviral therapy (ART), but the underlying
      mechanisms are unclear. Some features of HAND resemble those of age-associated
      cognitive decline in the absence of HIV, suggesting that overlapping mechanisms
      may contribute to neurocognitive impairment. DESIGN: Cross-sectional analysis of
      cerebrospinal fluid (CSF) from 100 individuals (46 HIV-positive patients and 54
      HIV-negative controls). METHODS: Untargeted CSF metabolite profiling was
      performed using liquid/gas chromatography followed by mass spectrometry. Cytokine
      profiling was performed by Bioplex. Bioinformatic analyses were performed in
      Metaboanalyst and R. RESULTS: Alterations in the CSF metabolome of HIV patients
      on ART mapped to pathways associated with neurotransmitter production,
      mitochondrial function, oxidative stress, and metabolic waste. Many CSF
      metabolites altered in HIV overlapped with those altered with advanced age in HIV
      negative controls, suggesting a pattern indicative of accelerated aging. Machine
      learning models identified neurotransmitters (glutamate, N-acetylaspartate),
      markers of glial activation (myo-inositol), and ketone bodies (beta
      hydroxybutyric acid, 1,2-propanediol) as top-ranked classifiers of HAND. These
      CSF metabolites correlated with worse neurocognitive test scores, plasma
      inflammatory biomarkers [interferon (IFN)-alpha, IFN-gamma, interleukin (IL)-8,
      IL-1beta, IL-6, IL-2Ra], and intrathecal IFN responses (IFN-gamma and kynurenine
      : tryptophan ratio), suggesting inter-relationships between systemic and
      intrathecal inflammation and metabolic alterations in CSF. CONCLUSIONS:
      Alterations in the CSF metabolome of HIV patients on ART suggest that persistent
      inflammation, glial responses, glutamate neurotoxicity, and altered brain waste
      disposal systems contribute to mechanisms involved in HAND that may be augmented
      with aging.

PMID- 24752086
TI  - [Biological behaviors of lung cancer stem-like cells from human large-cell lung
      cancer cell line H460].
AB  - OBJECTIVE: To isolate lung cancer stem-like cells (LCSCs) from human large-cell
      lung cancer cell line NCI-H460 (H460) and explore their biological
      characteristics. METHODS: H460 cells were cultured in serum-free medium in the
      presence of specific growth factors. Quantitative PCR (qPCR), flow cytometry and
      colony formation assay were performed to characterize the stemness of H460
      spheres. Adherent H460 cells and H460 cell spheres were inoculated subcutaneously
      in nude mice and the tumor growth was assessed. RESULTS: The isolated LCSCs from
      H460 cells in serum-free medium grew as floating cell spheres and exhibited
      stronger proliferative activity than H460 cells. Compared with H460 cells, H460
      cells spheres showed higher expressions of stem cell markers Sox2, Oct4, and
      especially Nanog, and possessed a stronger tumorigenicity in nude mice.
      CONCLUSION: The serum-free culture system can effectively enrich lung cancer stem
      cells from human lung cancer stem cell line H460, and the high expression of
      Nanog may importantly contribute to the maintenance of cancer stem cell-like
      properties of the isolated LCSCs.

PMID- 24752087
TI  - [Predictive value of lymph node ratio for postoperative distant metastasis of
      stage III colorectal cancer].
AB  - OBJECTIVE: To investigate the predictive value of metastatic lymph node ratio for
      postoperative distant metastasis in patients with colorectal cancer. METHODS: The
      clinicopathological data were collected from 180 patients with colorectal cancer
      who underwent surgical resection in General Hospital of PLA between from January,
      2007 to January, 2012. The patients were divided into 2 groups according to the
      presence of distant organ metastasis and the clinicopathological factors were
      analyzed with Chi-square test and logistic regression. RESULTS: Of the 118
      surgical patients enrolled, 118 were free of distant metastasis and 62 had
      distant metastasis involving the liver (39 cases), lungs (12 cases), and multiple
      organs (11 cases). The gross types, differentiation, ELN and LNR of the tumors
      differed significantly between the two groups. Logistic regression analysis
      showed that LNR was an independent factor correlating to distant metastasis of
      colorectal cancer. CONCLUSION: LNR is independently correlated with distant organ
      metastasis of colorectal cancer and serves as an important predicative factor for
      estimating the prognosis of colorectal cancer.

PMID- 24752088
TI  - [Changes of hypoxia-inducible factor in residual hepatocellular carcinoma
      following high-intensity focused ultrasound exposure in nude mice].
AB  - OBJECTIVE: To study the changes in hypoxia-inducible factor (HIF1alpha,
      HIF2alpha) in the residual tumor cells in nude mice bearing hepatocellular
      carcinoma (HCC) following treatment with high-intensity focused ultrasound
      (HIFU). METHODS: Thirty nude mice bearing human HCC received treatment with HIFU.
      At 1, 3, and 5 days and 1 and 2 weeks after the treatment, the mice were examined
      for pathological changes of the residual tumor with HE staining; SP
      immunohistochemistry, Western blotting and real-time quantitative PCR were used
      to detect the protein and mRNA expressions of HIF1alpha and HIF2alpha in the
      tumor. RESULTS: HE staining revealed the presence of residual tumor cells and
      large necrotic areas after the treatment. Immunohistochemistry showed a gradual
      increment of HIF1alpha protein and mRNA expressions after the treatment, reaching
      the peak level at 3 days (P<0.05) followed by progressive reduction at 5 days and
      1 and 2 weeks. HIF2alpha expressions at either the protein or mRNA levels
      exhibited no significant changes within 3 days after the treatment (P>0.05) but
      increased significantly at 5 days and 1 and 2 weeks (P<0.05). CONCLUSION: The
      changes of HIF1alpha and HIF2alpha in the residual tumor after HIFU treatment in
      nude mice bearing HCC can be associated with tumor cell apoptosis and
      angiogenesis after the treatment.

PMID- 24752089
TI  - [Association between CISH polymorphisms and susceptibility to chronic hepatitis B
      in Chinese Han population].
AB  - OBJECTIVE: To investigate the association between rs414171 single nucleotide
      polymorphisms (SNP) of cytokine- inducible src homology 2 domain protein (CISH)
      and the susceptibility to chronic hepatitis B. METHODS: A total of 233 Chinese
      Han patients with chronic hepatitis B and 148 age- and sex-matched healthy
      controls were enrolled in this case-control study. The SNP rs414171 was genotyped
      by Sequenom MassArray-IPLEX to analyze the relationship between rs414171 and
      chronic hepatitis B. RESULTS: The distribution of SNP rs414171 allele and
      genotype frequencies showed no significant difference between the patients and
      healthy controls (P>0.05). CONCLUSION: CISH rs414171 is not significantly
      associated with the susceptibility to chronic hepatitis B in Chinese Han
      population.

PMID- 24752090
TI  - [Assessment of renal function and risk factors for renal impairment in patients
      with hepatitis B virus-related liver cirrhosis].
AB  - OBJECTIVE: To evaluate the renal function in treatment-naive patients with
      hepatitis B virus (HBV) related cirrhosis and to identify the risk factors for
      renal impairment. METHODS: We collected the data of 860 HBV-related cirrhosis
      patients hospitalized in our unit between Jan 1, 2011 and Dec 31, 2011. Liver
      function of the patients was assessed with Child-Pugh score system, and the renal
      function with estimated glomerular filtration rate (eGFR) calculated by
      Modification of Diet in Renal Disease (MDRD) equation recommended by Kidney
      Disease Outcomes Quality Initiative (K/DOQI). We investigated the prevalence of
      renal impairment (eGFR>60 ml/min/1.73 m(2)) among these patients and explored the
      risk factors for renal impairment. RESULTS: Of the 860 patients, 296 had complete
      clinical data and were included in our analysis. The overall incidence of renal
      impairment among the enrolled patients was 8.45% (25/296). Patients with Child
      Pugh stage C showed a significantly higher incidence of renal impairment than
      those with stages B and A (17.17% [17/99] vs 6.67%[7/105] vs 1.09% [1/92],
      P<0.001). Age, history of hyperuricemia, and Child-Pugh score were identified as
      the risk factors for renal impairment in these patients. CONCLUSION: In patients
      with HBV-related liver cirrhosis, the incidence of renal impairment increases
      significantly with deterioration of the liver function, and renal function should
      be regularly monitored in these patients for appropriate antiviral treatment.

PMID- 24752091
TI  - [Calculated panel reactive antibody method for assessing the probability of
      kidney recipients to receive transplantation].
AB  - OBJECTIVE: To establish a calculated panel reactive antibody (CPRA) method to
      analyze the donor-recipient incompatibility rate in PRA-positive kidney
      recipients and estimate the probability of these recipients to receive kidney
      transplantation. METHODS: Based on the database of HLA-A, -B, -DR genes and A-B,
      A-DR, B-DR, A-B-DR haplotype frequencies collected from 2004 donors from Jan 2000
      to Dec 2012, we analyzed CPRA in 202 PRA-positive recipients and evaluated the
      consistency between PRA and CPRA assessments using a CPRA-Java calculator
      software, which returned a percentage of CPRA (representing the probability of
      unacceptable HLA in the donor group) after input of HLA-specific antibodies of a
      PRA-positive recipient. RESULTS: The mean PRA intensity of the 202 PRA-positive
      recipients was (23.12?17.83)% with a mean CPRA% of (46.07?23.30)%. A significant
      difference was found between the mean PRA% and CPRA% in low sensitized recipients
      (PRA 0-10%) [(6.87?2.41)% vs (21.63?11.75)%, P<0.05) and in moderately sensitized
      recipients (PRA 10%-30%) [(20.15?5.70)% vs (50.56?16.86)%, P<0.05), but not in
      highly sensitized recipients (PRA>30%); The concordance rates between PRA% and
      CPRA% in the 3 groups were 19.35% (P<0.05), 10.99% (P<0.05), and 100% (P>0.05),
      respectively. CONCLUSIONS: Lowly sensitized kidney recipients might have a lower
      probability of actually receiving a transplant than PRA% shows. A PRA%>30% is a
      risk factor for kidney transplantation. PRA reflects the sensitized level of a
      renal recipient, and reliable detection of HLA antibody specificity is of
      critical importance. CPRA accurately reflects the probability of a recipient to
      receive a transplant to assist clinicians in predicting the waiting time and
      selecting the transplant approach.

PMID- 24752092
TI  - [Sanhuangyinchi decoction pretreatment ameliorates acute hepatic failure in rats
      by suppressing antioxidant stress and caspase-3 expression].
AB  - OBJECTIVE: To observe the effects of Sanhuangyinchi decoction (SHYCD)
      pretreatment on acute hepatic failure (AHF) induced by D-galactosamine and
      lipopolysaccharide (LPS) in rats and explore the possible mechanisms involving
      antioxidant stress and cell apoptosis-related protein expression. METHODS: Forty
      eight SD rats were randomized equally into control group, AHF model group, high-,
      medium- and low-dose SHYCD groups, and Bicyclol group. Five days after
      administration of the corresponding drugs, the rats were challenged with
      peritoneal D-galactosamine (700 mg/kg) plus LPS (10 ug/kg) injections to induce
      AHF acute hepatic failure except for those in the control group. At 48 h after
      the injections, blood samples were collected from the rats to detect the levels
      of ALT, AST, TBIL, PT, INR and FIB, and pathological changes and superoxide
      dismutase (SOD) and malondialdehyde (MDA) contents in the liver were examined;
      immunohistochemistry and western blotting were used to detect caspase-3 protein
      expression in the liver. RESULTS: The levels of ALT, AST, TBIL, TP and INR in the
      3 SHYCD groups and Bicyclol group significantly decreased (P<0.05) while FIB
      significantly increased in comparison with those in the model group. SHYCD
      obviously ameliorated the pathological changes, enhanced SOD activity (P<0.05),
      and decreased MDA levels (P<0.05) and caspase-3 expression (P<0.05) in the liver
      tissue. SHYCD at the medium dose produced similar effects to Bicyclol (P>0.05)
      and showed better effects at the high dose than Bicyclol (P<0.05). CONCLUSION:
      SHYCD pretreatment can dose-dependently ameliorate AHF in rats possibly by
      suppressing antioxidant stress and caspase-3 expression to decrease hepatic cell
      apoptosis.

PMID- 24752093
TI  - [Development of a lung cancer vaccine by transfecting dendritic cells with
      rAAV/CEA].
AB  - OBJECTIVE: To study the feasibility of preparing a therapeutic lung cancer
      vaccine by transfecting dendritic cells (DCs) with adeno-associated virus vector
      carrying carcino-embryonic antigen gene (rAAV/CEA). METHODS: Adherent cells
      (monocytes) isolated from the peripheral blood of a healthy donor were infected
      with rAAV/CEA virus stock or pulsed with CEA peptide (control). The monocytes in
      both groups were induced into mature DCs with recombinant human GM-CSF, IL-4 and
      TNF-alpha. At day 7 of induction, the mature DCs were harvested and mixed with T
      lymphocytes. T cell proliferation stimulated by the DCs was assessed with (3)H
      thymidine uptake, and the expression of IL-4, IFN-gamma, CD8, CD4, CD25 and CD69
      in cytotoxic T lymphocytes (CTL) was analyzed with flow cytometry. The
      cytotoxicity of the CTL against the target CEA-positive lung cancer A549 cells
      was tested by (51)Cr releasing assay. RESULTS: The DCs transfected with rAAV/CEA
      strongly stimulated the proliferation of the T cell populations, and the induced
      CTL showed high expressions of CD8, CD69 and IFN-gamma. The transfected DCs
      exhibited a high killing ability of CEA-positive lung cancer cells, and the
      killing showed a CEA antigen specificity and was limited by MHC I. These results
      suggested the ability of rAAV/CEA-transfected DCs in generating specific cellular
      immunity in vitro. CONCLUSION: It is feasible to prepare therapeutic lung cancer
      vaccines by transfecting DCs with rAAV/CEA.

PMID- 24752095
TI  - [A modified approach to establishing a rat model of liver cancer with concurrent
      cirrhosis].
AB  - OBJECTIVE: To establish a modified rat model of liver cancer with concurrent
      cirrhosis for the study of carcinogenesis characteristics and drug intervention
      of liver cancer. METHODS: Fifty male Wistar rats weighing 100-120 g were randomly
      divided into normal control group (20 rats) and model group (30 rats). In the
      model group, the rats were subjected to intraperitoneal injection of 50 mg/kg DEN
      N-diethylnitrosamine (DEN) twice a week for 4 consecutive weeks, followed then by
      weekly injections for another 10 weeks. The control rats received injections of
      0.1 ml saline in the same manner. At 2, 4, 8, 12, 14, and 18 weeks, 3 rats from
      each group were sacrificed for assessing tumor formation and liver cirrhosis.
      RESULTS: Liver cancer with concurrent cirrhosis was induced successfully after 14
      weeks of DEN injections. At the 14th week, 3 out of the 5 rats were found to have
      cirrhosis and LC, and at the 18th week, all the 3 rats examined had cirrhosis and
      liver cancer. The total carcinogenesis rate in the rats was 75% at 18 weeks with
      an overall mortality of 33%. CONCLUSION: This approach to establishing rat models
      of liver cancer with concurrent cirrhosis requires simple operation, shortens the
      time of carcinogenesis, and ensures a high success rate of carcinogenesis and a
      low mortality rate. The carcinogenesis characteristics in this model are similar
      to those in human.

PMID- 24752094
TI  - [1,25-dihydroxyvitamin D3 pretreatment inhibits house dust mite-induced thymic
      stromal lymphopoietin release by human airway epithelial cells].
AB  - OBJECTIVE: To investigate the effect of 1,25-dihydroxyvitamin D3 (1,25VD3) on
      house dust mites (HDM)-induced expression of thymic stromal lymphopoietin (TSLP)
      in human airway epithelial cells in vitro. METHODS: Human airway epithelial 16HBE
      cells were incubated with 200, 400, and 800 U/L in the absence or presence of
      1,25VD3 (10(-8) mol/L) for 6 h and 24 h, and TSLP mRNA and protein expressions in
      the cells were assessed using quantitative PCR and ELISA. RESULTS: 16HBE cells
      incubated with HDM at 200, 400, and 800 U/L showed significantly increased TSLP
      mRNA and protein expressions (P<0.05). Pretreatment of the cells with 1,25VD3
      obviously lowered 400 U/L HDM-induced TSLP expressions (P<0.05), but 1,25VD3
      added along with HDM in the cells did not produce significant effects on TSLP
      expressions (P=0.58). CONCLUSION: Both 1,25VD3 and HDM can induce TSLP expression
      and release in 16HBE cells, but pretreatment with 1,25VD3 can decrease HDM
      augmented TSLP expression in the cells.

PMID- 24752096
TI  - [Value of dual-phase (18)F-FDG PET/CT in preoperative staging of bladder cancer].
AB  - OBJECTIVE: To investigate the clinical value of dual-phase (18)F-FDG PET/CT with
      oral diuretics in preoperative staging of bladder cancer. METHODS: The imaging
      data were analyzed of 73 patients with bladder cancer undergoing preoperative
      dual-phase (18)F-FDG PET/CT with oral diuretic between May, 2003 and May, 2012.
      All the patients underwent whole-body PET/CT scan 60 min after intravenous
      injection of 270-350 MBq of (18)F-FDG. Additional delayed pelvic PET/CT images
      were acquired after forced diuresis using oral furosemide (40 mg). All the
      patients underwent subsequent radical cystectomy, and (18)F-FDG PET/CT findings
      were compared with the histopathologic results to evaluate the value of dual
      phase (18)F-FDG PET/CT in preoperative staging. RESULTS: The concordance rate of
      dual-phase FDG PET/CT-based bladder cancer staging with the histopathologic
      results was 63.0% in the 73 patients, and was 100% (7/7) for pT4 bladder cancers.
      With dual-phase FDG PET/CT, the detection rate was 75.0% (6/8) for lymph node
      metastases, 100% (4/4) for distant metastases, and 100% (4/4) for other
      concurrent primary malignancies. CONCLUSION: Though with limited accuracy in T
      staging of pTa, pT1, pT2, and pT3 bladder cancer, dual-phase FDG PET/CT has
      important clinical value in staging of pT4 bladder cancer and in N-staging, M
      staging and detection of other concurrent primary malignancies.

PMID- 24752097
TI  - [Effect of exogenous hydrogen sulfide on BACE-1 enzyme expression and beta
      amyloid peptide metabolism in high-glucose primary neuronal culture].
AB  - OBJECTIVE: To investigate the effects of exogenous hydrogen sulfide (H2S) on beta
      site APP cleaving enzyme 1 (BACE-1) and beta-amyloid peptide (Abeta) metabolism
      in primary culture of neurons under high-glucose condition. METHODS: The cortical
      neurons in primary culture under normal and high glucose (60 mmol/L) conditions
      for 24 h were exposed to 25, 50 and 100 umol/L NaHS. Abeta1-42 concentration in
      the cell culture was measured by ELISA, and BACE-1 mRNA and protein levels were
      detected by fluorescent quantitative real-time PCR and Western blotting,
      respectively. RESULTS: Compared with the neurons cultured in normal glucose, the
      neurons exposed to high glucose showed significantly increased Abeta1-42
      concentration and BACE-1 mRNA and protein expressions (P<0.05). Exposure to 25,
      50 and 100 umol/L NaHS significantly decreased Abeta1-42 concentration and BACE-1
      mRNA and protein expressions in the high-glucose cell culture (P<0.05).
      CONCLUSION: Neurons exposed to high glucose exhibit increased Abeta1-42 levels
      and BACE-1 mRNA and protein expressions, which can be concentration-dependently
      decreased by NaHS.

PMID- 24752098
TI  - [SCF/c-Kit signaling promotes invasion of T24 cells via PI3K pathway].
AB  - OBJECTIVE: To explore the role of SCF/c-Kit signaling in the invasion of bladder
      cancer T24 cells. METHODS: Western blotting was used to detect the expression of
      c-Kit and PI3K pathway activation stimulated by stem cell factor (SCF) in T24
      cells. The invasiveness of T24 cells before and after SCF stimulation and
      Wortmannin (aspecific PI3K inhibitor) treatment was evaluated using Transwell
      invasion assay (direct and indirect counting methods). RESULTS: T24 cells
      expressed c-Kit protein and showed obvious Akt phosphorylation after stimulation
      with SCF (1 ng/ml) for 24 h. Compared to the control group, SCF stimulation (1
      ng/ml) caused a greater number of T24 cells to migrate through the polycarbonate
      film (P<0.01), and this effect was blocked by the application of Wortmannin
      before the stimulation. CONCLUSION: SCF/c-Kit signaling promotes the invasiveness
      of T24 cells, and this effect is mediated by the PI3K pathway.

PMID- 24752099
TI  - [Investigation of selective inhibition of digoxin derivative on retinoic acid
      related orphan nuclear receptor gammat transcription activity using molecular
      docking].
AB  - OBJECTIVE: Psoriasis is an autoimmune-related chronic inflammatory skin disease
      strongly associated with the dysfunction of Th17 cells. Retinoic acid-related
      orphan nuclear receptor gammat (RORgammat) plays a critical role in the
      differentiation and maturation of Th17 cells and in cell-derived immunologic
      derangement. We conducted this study to investigate potential mechanism by which
      the derivative of digoxin selectively antagonizes RORgammat transcriptional
      activity. METHOD: Using molecular docking in combination with molecular
      electrostatic potential (MEP), we detected the interaction between the derivative
      of digoxin (Dhd) and ROR transcription factor (RORalpha,RORbeta and RORgammat),
      and the results were further confirmed by bioluminescent assay. RESULT: Molecular
      docking demonstrated that Dhd could exclusively inhibit the conformation of
      RORgammat; bioluminescent assay further indicated that RORgammat was selectively
      antagonized by Dhd in a dose- and time-dependent manner. CONCLUSION: Dhd can
      selectively suppress RORgammat transcriptional activity.

PMID- 24752100
TI  - [Drug susceptibility and UL97 gene mutation analysis of cytomegalovirus in
      recipients of hematopoietic stem cell transplantation].
AB  - OBJECTIVE: To monitor human cytomegalovirus (HCMV) drug resistance in recipients
      of hematopoietic stem cell transplantation by phenotypic and genotypic methods.
      METHODS: HCMV clinical isolates was isolated from the urine of hematopoietic stem
      cell transplantation recipients treated with GCV. Tissue cell infection median
      dose (TCID50) of the isolates was calculated using Reed-Muench method, and their
      drug susceptibility was determined by plaque reduction assay. We amplified the
      UL97 DNA fragment of the virus by nested PCR followed by automated DNA
      sequencing. RESULTS: HCMV clinical strain isolated from the urine samples of the
      recipients using a human fibroblast cell line showed a TCID50 value of 10(
      4.618)/0.1 ml and a 50% inhibitory concentration (IC50) to GCV of 5.847 umol/L,
      suggesting its sensitivity to GCV. Alignment with the AD169 DNA reference
      sequence identified 4 point mutations of the virus at 1509 (T-C), 1575 (C-T),
      1794 (T-C), and 1815 (C-G), and only the last mutation resulted in one amino acid
      mutation to D605E. No gene mutation was found in relation to GCV resistance.
      CONCLUSIONS: Phenotypic and genotypic assays were established to examine
      antiviral drug resistance of HCMV in recipients of hematopoietic stem cell
      transplantation. We did not find any drug resistance of the clinical HCMV
      isolate.

PMID- 24752101
TI  - [Pathological and mammographic findings of microcalcification in calcified breast
      carcinoma without a mass].
AB  - OBJECTIVE: To explore the correlation between pathological findings and
      mammographic features of microcalcification in calcified breast carcinoma without
      a mass. METHODS: The morphology and distribution of the microcalcification
      lesions displayed by mammography were retrospectively analyzed in 108 cases of
      the calcified breast carcinoma without a mass in comparison with the pathological
      findings of the lesions. RESULTS: The mammographic morphology or distribution of
      the microcalcification lesions did not differ significantly across different
      pathological types of calcified breast carcinoma without a mass (P>0.05). The
      microcalcification lesions showed no significant morphological difference between
      invasive and noninvasive breast carcinomas (P>0.05). Fine pleomorphic
      calcifications were frequently found in both invasive and noninvasive breast
      carcinomas, but fine linear and fine linear branching calcifications and mixed
      malignant calcifications were more common in invasive breast carcinoma. The
      distribution of the microcalcifications showed significantly different patterns
      between invasive and noninvasive breast carcinoma (P=0.006), characterized by
      segmental and cluttered distributions of the lesions, respectively. CONCLUSION:
      There is no specific mammographic features in correlation with the pathological
      types of microcalcification lesions in calcified breast carcinoma without a mass,
      but invasive and noninvasive calcified breast carcinomas have different
      mammographic features in the morphology and distribution of the
      microcalcifications to allow their preoperative differentiation.

PMID- 24752102
TI  - [Effect of preoperative anxiety level on postoperative pain sensation in patients
      receiving implant denture for partial edentulism].
AB  - OBJECTIVE: To explore the effect of preoperative anxiety level on postoperative
      pain sensation in partially edentulous patients undergoing surgery for implant
      denture. METHODS: Eighty partially edentulous patients receiving implant denture
      were examined for preoperative anxiety level using State Trait Anxiety Inventory
      (STAI) and Modified Dental Anxiety Scale (MDAS) questionnaires before
      implantation surgery. The Visual Analogue Scale (VAS) and Present Pain Intensity
      (PPI) Questionnaire were used to assess the pain sensation in patients
      immediately after the operation. The correlations of preoperative state anxiety,
      trait anxiety, and dental anxiety with postoperative VAS score were analyzed.
      According to the assessment results of STAI, the patients were divided into
      little or no (score range 20-37) anxiety group (L group), moderate (38-44)
      anxiety group (M group), and high (45-80) anxiety group (H group) to analyze the
      effect of state anxiety and trait anxiety levels on postoperative pain sensation.
      RESULTS: Significantly positive correlations were found between preoperative
      state anxiety, trait anxiety and dental anxiety among the patients (P<0.01).
      Postoperative VAS score was positively correlated with trait anxiety score
      (P<0.01) and differed significantly between different trait anxiety groups
      (P<0.01). Compared with the patients in M and L groups, those in H group showed a
      significantly higher VAS score after the operation (P<0.05). CONCLUSION: The
      preoperative trait anxiety level is associated with postoperative pain sensation
      in partially edentulous patients receiving implant denture, suggesting the
      necessity of preoperative anxiety intervention in clinical practice.

PMID- 24752103
TI  - [Simultaneous isolation and primary culture of rat hepatocytes, hepatic stellate
      cells, Kupffer's cells and hepatic sinus endothelial cells].
AB  - OBJECTIVE: To establish a method for simultaneous isolation and primary culture
      of rat hepatocytes, hepatic stellate cells, Kupffer's cells and hepatic sinus
      endothelial cells. METHODS: By combining in situ perfusion, in vitro perfusion,
      density gradient centrifugation and differential adhesion, primary rat
      hepatocytes, hepatic stellate cells, Kupffer's cells and hepatic sinus
      endothelial cells were obtained. The purity of these cells were assessed with
      morphological observation, immunofluorescent staining and ink phagocytosis assay.
      RESULTS: We successfully obtained the 4 primary cells simultaneously by combining
      in situ perfusion with in vitro perfusion, density gradient centrifugation, and
      differential attachment. The cell yield rate, cell viability and purity all met
      requirements for the subsequent cell experiment. CONCLUSION: The combined cell
      isolation and culture method is feasible to isolate primary rat hepatocytes,
      hepatic stellate cells, Kupffer's cells and hepatic sinus endothelial cells
      simultaneously.

PMID- 24752104
TI  - [Intraperitoneal injection via a paravertebral approach in rabbits].
AB  - OBJECTIVE: To explore a simple and reliable method for intraperitoneal injection
      through a paravertebral approach in rabbits. METHODS: Sixty New Zealand rabbits
      were randomized into conventional group and modified groups to receive
      intraperitoneal injections through conventional and paravertebral approaches,
      respectively. In the conventional group, the injection site was on the abdominal
      wall 3~4 cm lateral from the umbilicus bilaterally, while that in the modified
      group was located dorsally at L5/L6 level 3-4 cm lateral from the midline.
      Abdominal CT scan was performed in the post-injection rabbits, which were
      sacrificed after 24 h for abdominal dissection. RESULTS: Success with a single
      puncture was achieved in 13 out of the 20 rabbits in the conventional group, and
      the rest required at least two punctures, with a mean rank sum of 23.50. With the
      modified approach, a single attempt was successful in all the 40 rabbits, with a
      mean rank sum of 34.0, showing a significant difference between the two groups
      (P<0.01). The success rates of a single injection differed significantly between
      the two groups (P<0.01). CT scan and abdominal dissection showed that the
      injection site with the modified approach was far away from the vital organs and
      large vessels with less peritoneal hyperemia and exudation. CONCLUSION:
      Paravertebral intraperitoneal paracentesis is a convenient and reliable method
      for intraperitoneal injection in rabbits.

PMID- 24752105
TI  - [Relationship between collateral circulation and cardiac function recovery in
      patients receiving percutaneous coronary intervention for a single left anterior
      descending artery].
AB  - OBJECTIVE: To explore the relationship between coronary collateral circulation
      following percutaneous coronary intervention (PCI) for a single left anterior
      descending artery and the recovery of cardiac function. METHODS: A total of 625
      patients with coronary heart disease were retrospectively analyzed, who received
      selective coronary angiography demonstrating lesions involving a single left
      anterior descending artery and underwent stent placement between January, 2010
      and December, 2012. According to Rentrop's classification, the patients were
      divided into group A (n=280) with Rentrop grades 1-3 and group B (n=325) with
      Rentrop grade 0. Group A were further divided into 3 subgroups according to the
      source of collateral circulation, namely group A1 (n=200) with contralateral
      collateral circulation, group A2 (n=44) with contralateral+ ipsilateral
      collateral circulation, and group A3 (n=36) with ipsilateral collateral
      circulation. The outcomes of cardiac function recovery were compared between
      groups A and B and between the 3 subgroups in group A. RESULTS: Compared with
      patients without collateral circulation, patients with collateral coronary
      circulation showed greater left ventricular ejection fraction increment and
      reduction in brain natriuretic peptide and red cell volume distribution width
      with also lower expansion left ventricular end-diastolic volume. Among the 3
      subgroups in group A, cardiac function improvement was the most obvious in
      patients with contralateral+ ipsilateral collateral circulation (group A2)
      followed by those in group A3, and was the worst in group A1. CONCLUSION: The
      presence of collateral coronary circulation promotes cardiac function recovery in
      patients receiving PCI for lesions involving a single left anterior descending
      artery. Patients with contralateral+ipsilateral collateral circulation have the
      best cardiac function improvement followed by those with contralateral collateral
      circulation.

PMID- 24752106
TI  - [Role of Sam68 in proliferation, invasion and migration of colorectal cancer
      cells in vitro].
AB  - OBJECTIVE: To investigate the role of Sam68 (Src-associated substrate during
      mitosis 68 kD) in the occurrence and development of colorectal cancer. METHODS:
      Colorectal cancer cell lines with stable Sam68 over-expressing and low Sam68
      expression were established to test the effect of Sam68 in the proliferation,
      invasion, and migration of the cancer cells using colony formation, MTT and
      Transwell assays. RESULTS: SW480 and Ls174t colorectal cell lines over-expressing
      Sam68 showed significantly enhanced cell proliferation, invasion and migration
      (P<0.05). Conversely, the low Sam68 expression in SW620 and HCT116 colorectal
      cell lines significantly suppressed the cell proliferation, invasion and
      migration (P<0.05). CONCLUSION: The expression of Sam68 can promote the
      proliferation, invasion and migration of colorectal cancer cells lines in vitro.

PMID- 24752107
TI  - [Polymorphisms of intercellular adhesion molecule-1 gene K469E and platelet
      endothelial cell adhesion molecule-1 gene C373G in patients with preeclampsia].
AB  - OBJECTIVE: To investigate the distributions of genotypic and allelic frequencies
      of intercellular adhesion molecule-1 (ICAM-1) gene K469E and platelet endothelial
      cell adhesion molecule-1 (PECAM-1) gene C373G in patients with preeclampsia.
      METHODS: Polymerase chain reaction-restriction fragment length polymorphism(PCR
      RFLP) and DNA sequencing were used for detecting ICAM-1 gene K469E and PECAM-1
      gene C373G genotypes in 110 women with preeclampsia and 110 normotensive pregnant
      women in comparison with their clinical characteristics. ESULTS: The
      distributions of observed and expected genotype frequencies were consistent with
      Hardy-Weinberg equilibrium. No significant differences were found in the genotype
      and allele frequencies of ICAM-1 gene K469E between the two groups (P>0.05), but
      the CC and the CG genotype frequencies of PECAM-1 gene C373G were significantly
      different between them (P<0.05). The relative risk for preeclampsia of CG
      genotype was 1.959 folds of that in CC genotype carriers (OR=1.959, 95%CI: 1.090
      3.520, P=0.024), and this association still existed after adjustment for age,
      gravidity, parity and BMI in logistic regression models. The C373G allele
      frequencies showed no significant difference between the two groups (P>0.05).
      CONCLUSIONS: The CG genotype of PECAM-1 gene C373G genetically predispose the
      carriers to preeclampsia, while ICAM-1gene K469E polymorphisms is not associated
      with preeclampsia.

PMID- 24752108
TI  - [Correlation between TMEM39A gene polymorphism and systemic lupus erythematosus
      in Chinese Han patients].
AB  - OBJECTIVE: To investigate the association between single nucleotide polymorphisms
      (SNPs) of the transmembrane protein 39A (TMEM39A) at the loci 1880G/A, 2442T/G,
      and 2456A/T and systemic lupus erythematosus (SLE) in Chinese Han patients.
      METHODS: TMEM39A gene polymorphisms at 3 loci (1880G/A, 2442T/G, 2456 A/T) were
      analyzed using polymerase chain reaction-restriction fragment length polymorphism
      (PCR-RFLP) in 110 Chinese Han patients with SLE and 80 normal control subjects,
      and the allele and genotype frequencies were compared by Chi-square test between
      the two groups. RESULTS: Both the genotype frequencies (AA, GA and GG) and allele
      frequencies (A and G) at 1880G/A differed significantly between SLE cases and the
      normal controls (P=0.002 and P=0.044, respectively). The two groups also showed
      significant differences in the genotype frequencies (GG, TG and TT) (P=0.001) and
      allele frequencies (G and T) (P=0.041) at 2442T/G. No significant differences
      were found in the genotype frequencies (TT, AT and AA) or allele frequencies (T
      and A) at 2456A/T between the two groups (P>0.05). The allele and genotype
      frequencies of the 3 SNPs showed no significant differences between lupus
      nephritis (LN) patients and non-LN patients. CONCLUSION: The TMEM39A
      polymorphisms at 1880G/A and 2442T/G, but not at 2456 A/T gene, may be associated
      with the susceptibility to SLE in Chinese Han population. The genotype or allele
      frequencies of the 3 SNPs have no effect on the incidence of lupus nephritis.

PMID- 24752109
TI  - [Neuropad test for sudomotor function to predict the risk of diabetic foot
      ulceration].
AB  - OBJECTIVE: To assess the predictive value of Neuropad test on occurrence of
      diabetic foot ulceration (DFU) among type 2 diabetic patients. METHODS: We
      divided 725 cases of type 2 diabetic patients into the high-risk and the non-high
      risk groups of DFU based on the results of vibration perception thresholds(VPT)
      examination, which was widely used as a criteria for predicting DFU. Receiver
      operating characteristic (ROC) analysis was used to compare the effectiveness of
      Neuropad with 10 g Semmes-Weinstein monofilament (10 g SWMF) testing in
      predicting the risk of DFU. RESULTS: Among 725 patients of type 2 diabetes, 6.1%
      were at a high risk of DFU. Compared to non-high-risk group, patients in high
      risk group had older age, longer diabetes duration, higher values of complete
      colour change time (CCC time) of Neuropad and higher abnormal rate of 10 g SWMF
      (P<0.01). CCC time of Neuropad was shown to be better in predicting the risk of
      DFU than 10 g SWMF, and the area under the ROC curve was about 0.8, and the best
      cut-off value was 22.25 min. CONCLUSION: Neuropad is an effective means for
      predicting of the risk of DFU, and can be used to prevent diabetic foot
      ulceration.

PMID- 24752110
TI  - [Clinical outcomes and economic analysis of two ovulation induction protocols in
      patients undergoing repeated IVF/ICSI cycles].
AB  - OBJECTIVE: To compare the clinical outcomes and cost-effectiveness of luteal
      phase down-regulation with gonadotrophin-releasing hormone (GnRH) agonist
      protocol and GnRH antagonist protocol in patients undergoing repeated in vitro
      fertilization and intracytoplasmic sperm injection (IVF-ICSI) cycles. METHODS: A
      retrospective analysis of clinical outcomes and costs was conducted among 198
      patients undergoing repeated IVF-ICSI cycles, including 109 receiving luteal
      phase down-regulation with GnRH agonist protocol (group A) and 89 receiving GnRH
      antagonist protocol (group B). The numbers of oocytes retrieved and good embryos,
      clinical pregnancy rate, abortion rate, the live birth rate, mean total cost, and
      the cost-effective ratio were compared between the two groups. RESULTS: In
      patients undergoing repeated IVF-ICSI cycles, the two protocols produced no
      significant differences in the number of good embryos, clinical pregnancy rate,
      abortion rate, or twin pregnancy rate. Compared with group B, group A had better
      clinical outcomes though this difference was not statistically significant. The
      number of retrieved oocytes was significantly greater and live birth rate
      significantly higher in group A than in group B (9.13=4.98 vs 7.11=4.74, and
      20.2% vs 9.0%, respectively). Compared with group B, group A had higher mean
      total cost per cycle but lower costs for each oocyte retrieved (2729.11 vs
      3038.60 RMB yuan), each good embryo (8867.19 vs 9644.85 RMB yuan), each clinical
      pregnancy (77598.06 vs 96139.85 RMB yuan). CONCLUSION: For patients undergoing
      repeated IVF/ICSI cycle, luteal phase down-regulation with GnRH agonist protocol
      produces good clinical outcomes with also good cost-effectiveness in spite an
      unsatisfactory ovarian reserve.

PMID- 24752111
TI  - [Clinical pathway management of acute exacerbations of chronic obstructive
      pulmonary disease based on state machine].
AB  - We propose a clinical pathway of acute exacerbations of chronic obstructive
      pulmonary disease (AECOPD) based on state machine. Clinical event-driven response
      was utilized to control workflow execution of the AECOPD clinical pathway. By
      comparison with the traditional clinical pathway management, clinical numerical
      results showed that the proposed method was better in hospitalization days,
      average hospitalization expense and aberration rate, and better handled the
      variability in the AECOPD clinical pathway execution. 

PMID- 24752112
TI  - [A clinical trial of ketogenic diet in patients with acute spinal cord injury:
      safety and feasibility].
AB  - OBJECTIVE: To conduct a clinical trial of ketogenic diet (KD) in patients with
      acute spinal cord injury (SCI) and evaluate its safety and feasibility by
      measuring blood ketone bodies and blood glucose levels. METHOD: Ten patients with
      acute SCI were recruited in the trial during the period from May, 2012 to
      October, 2013. The patients received a standard KD after fasting for 48 h. The
      levels of blood ketone, blood glucose and uric ketone were tested daily, and
      routine blood examination, electrolytes, liver and kidney function, body mass
      index (BMI), sensory and motor function, and adverse reactions were monitored
      weekly to assess the safety and feasibility of KD. RESULTS: KD treatment lasted
      for a mean of 12.9 days (4 to 29 days) in these patients. In all the patients,
      blood ketone level increased during the fasting and maintained a level above 2.0
      mmol/L after taking KD, while the uric ketone level ranged from +++ to ++++. The
      blood glucose level was in the normal range during KD. Except for blood chloride
      level and BMI, routine blood test results, electrolytes, liver and kidney
      function showed no significant changes after KD. No significant changes were
      observed in the sensation of light touch and pinprick. The average motor ASIA
      score increased from 33.3 to 35.1 after KD. Gastrointestinal dysfunction
      (diarrhea, nausea, poor appetite, gastric pain, and abdominal distension) was
      recorded in 5 patients, hypoglycemia occurred in one patient early after KD, and
      one patient experienced urticaria during KD. All the adverse reactions were
      relieved after symptomatic treatments. CONCLUSION: This preliminary clinical
      trial demonstrated that KD could increase ketone bodies level and maintain a
      normal blood glucose level, suggesting its safety and feasibility in patients
      with acute SCI.

PMID- 24752113
TI  - [Current status and clinical trials of laparoendoscopic single-site colorectal
      surgery].
AB  - The authors summarize the current techniques of laparoendoscopic single-site
      colorectal surgery in light of choice of abdominal incisions, single-site
      platform and instrument. System analysis suggests that laparoendoscopic single
      site colorectal surgery is safe and feasible, and its short term result is
      similar to that of conventional laparoscopy. However, further trials are needed
      to investigate its potential benefits and long-term oncologic outcomes. 

PMID- 24752114
TI  - [Whole esophagus deep burns with a metal foreign body in the stomach: a case
      report].
AB  - Whole esophagus deep burn is an extremely rare upper gastrointestinal tract
      disease. We report a case of severe burns of involving extensive body skin, eyes,
      throat, and esophagus. Endoscopic examination revealed acute necrotizing
      esophagitis and detected a metal foreign body in the stomach. The patient
      underwent burn wound debridement with analgesia, anti-shock rehydration, anti
      infection, and symptomatic treatments, which failed to improve the conditions.
      The patient died of respiratory and circulatory failure secondary to serious
      sepsis. 

PMID- 24752115
TI  - [Serum follicle-stimulating hormone in combination with serum inhibin B evaluates
      spermatogenesis of azoospermic men].
AB  - OBJECTIVE: This study is in an attempt to evaluate the diagnostic significance to
      predict the spermatogenesis of azoospermic men in examination of serum follicle
      stimulating hormone (FSH) combination with serum inhibin B (INHB). METHODS:
      Quantitative examination of serum FSH and INHB was performed in 95 case of
      azoospermic men. According to their classifications of testicular biopsy with
      histopathological examination, there were 20 patients of Sertoli cell only, 25 of
      hypospermatogenesis, 18 of spermatogenic maturation arrest (complete or
      incomplete), and 32 of normal spermatogenesis. The association of serum FSH and
      INHB levels with histopathological classifications were analyzed by using
      statistical software. RESULTS: Serum FSH, INHB and INHB/FSH levels of Sertoli
      cell only differed with statistical significance from hypospermatogenesis,
      spermatogenic maturation arrest and normal spermatogenesis (P<0.05). FSH, in
      which there were no statistical significance among the latter three
      classifications (P>0.05). Serum FSH, INHB and INHB/FSH levels were no
      relationship with maturation arrest (P>0.05), but were negatively related to the
      other classifications (P<0.05). INHB level less than 28.55 pg/ml predicted
      Sertoli cell only in a sensitivity of 97% and a specificity of 85%. CONCLUSION:
      Serum FSH and INHB levels is ineffective to distinguish the spermatogenic
      classifications from azoospermic men, but they are available to confirm the
      disease of Sertoli cell only. The other abnormalities of azoospermic men is also
      dependent on bioptic histopathology to confirm the subtypes.

PMID- 24752116
TI  - [Application of three-dimensional high-definition laparoscope in laparoscopic
      radical resection of gastric cancer].
AB  - OBJECTIVE: To investigate the clinical value of three-dimensional (3D) high
      definition (HD) laparoscope in laparoscopic radical resection of gastric cancer.
      METHODS: From January to December, 2013, 40 patients underwent radical resection
      of gastric cancer with 3D HD laparoscopy (3D group) and another 40 patients
      received 2D HD laparoscopy (2D group). The duration of surgery, intra-operative
      blood loss, learning curve, and costs during hospitalization were compared
      between the two groups. RESULTS: The average operation duration of 3D group was
      2.8=0.6 h, significantly shorter that in the 2D group (3.2=0.8 h, P<0.05); the
      intraoperative blood loss in the 3D group was significantly less than that in the
      2D group (110=18 ml vs 120=21 ml, P>0.05). The mean hospitalization cost was 75
      000=16 000 RMB Yuan in 3D group, similar to significantly lower than that of 71
      000=13 000 RMB Yuan in 2D group (P>0.05). CONCLUSION: 3D HD laparoscopy can
      provide three-dimensional vision and better sense of depth to facilitate precise
      operation and shorten the operation time. The high-definition 3D vision also
      allows surgeons to quickly improve surgical skills and shorten the learning
      curve.

PMID- 24752117
TI  - [Postoperative rehabilitation strategy for acetabular fracture: application of 3D
      printing technique].
AB  - OBJECTIVE: To explore the value of 3D printing technique in the surgical
      management and strategy of rehabilitation therapy of acetabular fracture.
      METHODS: For a patient with acetabular fracture, the pelvis model was printed
      preoperatively by 3D printing technique for surgical simulation to determine the
      optimal position of the screw, measure the screw length, and design the route of
      screw entry. Laparoscopic assisted internal fixation was performed, and a gradual
      and systematic rehabilitation plan was carried out after the surgery based on the
      results of simulation. RESULTS: The operation was completed successfully with a
      shortened postoperative recovery time. CONCLUSIONS: The application of 3D
      printing allows more accurate and safer surgical management of acetabular
      fracture to promote postoperative recovery of the patient and lower the medical
      costs.

PMID- 24752118
TI  - [Research progress of three-dimensional laparoscope system].
AB  - The lack of depth perception and spatial orientation in two-dimensional image of
      traditional laparoscopy require long-term training of the surgeons. Three
      dimensional (3D) laparoscopy provides stereoscopic visions as compared to
      monocular views in a traditional laparoscopic system. In this review, the authors
      summarize the clinical application of 3D laparoscopy and its current research
      progress. 

PMID- 24752122
TI  - Epilepsy: population-based study reinforces the link between autoimmune disease
      and epilepsy.

PMID- 24752119
TI  - Lifetime induced abortion: a comparison between women living and not living with
      HIV.
AB  - BACKGROUND: Studies aimed at understanding the association between induced
      abortion and HIV are scarce and differ on the direction of the association. This
      paper aims to show the prevalence of induced abortion in a sample of pregnancies
      of women living and not living with HIV/Aids, determining variables associated
      with pregnancy termination and linked to the life course of women and to the
      specific context of the pregnancy. METHODS: Data came from a cross-sectional
      study, using interviewer-administered questionnaire, developed with women that
      attended public health services in Porto Alegre, Brazil. A generalized estimating
      equation model with logit link measured the association between determinants and
      abortion. FINDINGS: The final sample was composed of 684 women living with
      HIV/Aids (2,039 pregnancies) and 639 women not living with HIV/Aids (1,539
      pregnancies). The prevalence of induced abortion among pregnancies in women
      living with HIV/Aids was 6.5%, while in women not living with HIV/Aids was 2.9%.
      Among women living with HIV/Aids, the following were associated with induced
      abortion in the multivariable analysis: being older, having a higher education
      level, having had more sexual partners (i.e., variables linked to the life course
      of women), having had children prior to the index pregnancy and living with a
      sexual partner during pregnancy (i.e., variables linked to the context of each
      pregnancy). On the other hand, among women not living with HIV/Aids, only having
      a higher education level and having had more sexual partners (i.e., determinants
      linked to the life course of women) were associated with voluntary pregnancy
      termination in multivariable analysis. CONCLUSION: Although determinants are
      similar between women living and not living with HIV/Aids, prevalence of induced
      abortion is higher among pregnancies in women living with HIV/Aids, pointing to
      their greater social vulnerability and to the need for public policy to address
      prevention and treatment of HIV associated with reproductive issues.

PMID- 24752125
TI  - Epilepsy: preserving memory in temporal lobectomy-are networks the key?

PMID- 24752120
TI  - Mechanisms of sudden unexpected death in epilepsy: the pathway to prevention.
AB  - Sudden unexpected death in epilepsy (SUDEP) is the leading cause of death in
      patients with refractory epilepsy, with an estimated 35% lifetime risk in this
      patient population. There is a surprising lack of awareness among patients and
      physicians of this increased risk of sudden death: in a recent survey, only 33%
      of Canadian paediatricians who treated patients with epilepsy knew the term
      SUDEP. Controversy prevails over whether cardiac arrhythmia or respiratory arrest
      is more important as the primary cause of death. Effective preventive strategies
      in high-risk patients will rely on definition of the mechanisms that lead from
      seizures to death. Here, we summarize evidence for the mechanisms that cause
      cardiac, respiratory and arousal abnormalities during the ictal and postictal
      period. We highlight potential cellular mechanisms underlying these
      abnormalities, such as a defect in the serotonergic system, ictal adenosine
      release, and changes in autonomic output. We discuss genetic mutations that cause
      Dravet and long QT syndromes, both of which are linked with increased risk of
      sudden death. We then highlight possible preventive interventions that are likely
      to decrease SUDEP incidence, including respiratory monitoring in epilepsy
      monitoring units and overnight supervision. Finally, we discuss treatments, such
      as selective serotonin reuptake inhibitors, that might be personalized to a
      specific genetic or pathological defect. 

PMID- 24752126
TI  - Neurosurgery: Psychosurgery guidelines--friction between ideal and reality?

PMID- 24752127
TI  - Epilepsy: responsive neurostimulation-modulating the epileptic brain.

PMID- 24752129
TI  - Alzheimer disease: advances in imaging of AD biomarkers could aid early
      diagnosis.

PMID- 24752130
TI  - Pregnancy outcome after the treatment of loop electrosurgical excision procedure
      or cold-knife conization for cervical intraepithelial neoplasia.
AB  - OBJECTIVE: The aim of this study was to investigate the influence on fertility
      and pregnancy outcome in cervical intraepithelial neoplasia (CIN) patients after
      a loop electrosurgical excision procedure (LEEP) or cold-knife conization (CKC).
      METHODS: 269 patients with CIN-II-III who wanted to conceive were prospectively
      enrolled in this randomized clinical trial to receive either the LEEP or CKC
      procedure. Fertility, neonatal and maternal outcomes were observed and compared.
      RESULTS: 244 evaluable patients were divided into two groups. There were 124 in
      the LEEP group and 120 in the CKC group. The preterm premature rupture of
      membranes (16 vs. 8%; p = 0.03), preterm delivery rate (11 vs. 5%; p = 0.04) and
      low birth weight infants rate (<2,500 g) (10 vs. 6%; p = 0.04) were higher in the
      CKC group than in the LEEP group, but there was no difference in mean birth
      weight, cesarean delivery, labor induction, or neonatal intensive care unit
      admission. There was no case of neonatal mortality. CONCLUSIONS: In a prospective
      evaluation the findings of this study demonstrate that LEEP is safer for future
      pregnancies when compared to CKC. LEEP should be an appropriate choice for
      patients with CIN who want to become pregnant later in life.

PMID- 24752131
TI  - Comparing stochastic differential equations and agent-based modelling and
      simulation for early-stage cancer.
AB  - There is great potential to be explored regarding the use of agent-based
      modelling and simulation as an alternative paradigm to investigate early-stage
      cancer interactions with the immune system. It does not suffer from some
      limitations of ordinary differential equation models, such as the lack of
      stochasticity, representation of individual behaviours rather than aggregates and
      individual memory. In this paper we investigate the potential contribution of
      agent-based modelling and simulation when contrasted with stochastic versions of
      ODE models using early-stage cancer examples. We seek answers to the following
      questions: (1) Does this new stochastic formulation produce similar results to
      the agent-based version? (2) Can these methods be used interchangeably? (3) Do
      agent-based models outcomes reveal any benefit when compared to the Gillespie
      results? To answer these research questions we investigate three well-established
      mathematical models describing interactions between tumour cells and immune
      elements. These case studies were re-conceptualised under an agent-based
      perspective and also converted to the Gillespie algorithm formulation. Our
      interest in this work, therefore, is to establish a methodological discussion
      regarding the usability of different simulation approaches, rather than provide
      further biological insights into the investigated case studies. Our results show
      that it is possible to obtain equivalent models that implement the same
      mechanisms; however, the incapacity of the Gillespie algorithm to retain
      individual memory of past events affects the similarity of some results.
      Furthermore, the emergent behaviour of ABMS produces extra patters of behaviour
      in the system, which was not obtained by the Gillespie algorithm. 

PMID- 24752132
TI  - Affective temperaments contribute to cardiac complications in hypertension
      independently of depression.

PMID- 24752133
TI  - Alcohol enhances Acinetobacter baumannii-associated pneumonia and systemic
      dissemination by impairing neutrophil antimicrobial activity in a murine model of
      infection.
AB  - Acinetobacter baumannii (Ab) is a common cause of community-acquired pneumonia
      (CAP) in chronic alcoholics in tropical and sub-tropical climates and associated
      with a >50% mortality rate. Using a murine model of alcohol (EtOH)
      administration, we demonstrated that EtOH enhances Ab-mediated pneumonia leading
      to systemic infection. Although EtOH did not affect neutrophil recruitment to the
      lungs of treated mice, it decreased phagocytosis and killing of bacteria by these
      leukocytes leading to increased microbial burden and severity of disease.
      Moreover, we determined that mice that received EtOH prior to Ab infection were
      immunologically impaired, which was reflected in increased pulmonary
      inflammation, sequential dissemination to the liver and kidneys, and decreased
      survival. Furthermore, immunosuppression by EtOH was associated with deregulation
      of cytokine production in the organs of infected mice. This study establishes
      that EtOH impairs immunity in vivo exacerbating Ab infection and disease
      progression. The ability of Ab to cause disease in alcoholics warrants the study
      of its virulence mechanisms and host interactions. 

PMID- 24752134
TI  - Lack of salt-inducible kinase 2 (SIK2) prevents the development of cardiac
      hypertrophy in response to chronic high-salt intake.
AB  - Cardiac left ventricle hypertrophy (LVH) constitutes a major risk factor for
      heart failure. Although LVH is most commonly caused by chronic elevation in
      arterial blood pressure, reduction of blood pressure to normal levels does not
      always result in regression of LVH, suggesting that additional factors contribute
      to the development of this pathology. We tested whether genetic preconditions
      associated with the imbalance in sodium homeostasis could trigger the development
      of LVH without concomitant increases in blood pressure. The results showed that
      the presence of a hypertensive variant of alpha-adducin gene in Milan rats
      (before they become hypertensive) resulted in elevated expression of genes
      associated with LVH, and of salt-inducible kinase 2 (SIK2) in the left ventricle
      (LV). Moreover, the mRNA expression levels of SIK2, alpha-adducin, and several
      markers of cardiac hypertrophy were positively correlated in tissue biopsies
      obtained from human hearts. In addition, we found in cardiac myocytes that alpha
      adducin regulates the expression of SIK2, which in turn mediates the effects of
      adducin on hypertrophy markers gene activation. Furthermore, evidence that SIK2
      is critical for the development of LVH in response to chronic high salt diet (HS)
      was obtained in mice with ablation of the sik2 gene. Increases in the expression
      of genes associated with LVH, as well as increases in LV wall thickness upon HS,
      occurred only in sik2+/+ but not in sik2-/- mice. Thus LVH triggered by HS or the
      presence of a genetic variant of alpha-adducin requires SIK2 and is independent
      of elevated blood pressure. Inhibitors of SIK2 may constitute part of a novel
      therapeutic regimen aimed at prevention/regression of LVH. 

PMID- 24752135
TI  - Psoriasis beyond the skin: a review of the literature on cardiometabolic and
      psychological co-morbidities of psoriasis.
AB  - Psoriasis is increasingly associated with a range of co-morbid diseases and risk
      factors. Patients with co-morbidities are more likely to need hospitalisation for
      non-dermatological conditions, and incur greater total costs than those without
      co-morbidities. A literature review was conducted on two of the most common co
      morbidities of psoriasis (cardiovascular (CV) and psychological co-morbidities),
      to establish their incidence and impact and to raise awareness of unanswered
      questions and highlight knowledge gaps. A large number of small controlled or
      cross-sectional studies report increased prevalence of cardiometabolic and
      psychological co-morbidities in psoriasis patients. A number of large cohort
      studies documented the incidence of various cardiometabolic co-morbidities.
      Severe psoriasis is associated with increased mortality, and the most common
      cause of death is CV disease. Studies on the management of co-morbidities and
      their impact on psoriasis treatment are scarce. Many questions on the co
      morbidities of psoriasis remain to be answered. 

PMID- 24752136
TI  - Consequences of a human TRPA1 genetic variant on the perception of nociceptive
      and olfactory stimuli.
AB  - BACKGROUND: TRPA1 ion channels are involved in nociception and are also excited
      by pungent odorous substances. Based on reported associations of TRPA1 genetics
      with increased sensitivity to thermal pain stimuli, we therefore hypothesized
      that this association also exists for increased olfactory sensitivity. METHODS:
      Olfactory function and nociception was compared between carriers (n = 38) and non
      carriers (n = 43) of TRPA1 variant rs11988795 G>A, a variant known to enhance
      cold pain perception. Olfactory function was quantified by assessing the odor
      threshold, odor discrimination and odor identification, and by applying 200-ms
      pulses of H2S intranasal. Nociception was assessed by measuring pain thresholds
      to experimental nociceptive stimuli (blunt pressure, electrical stimuli, cold and
      heat stimuli, and 200-ms intranasal pulses of CO2). RESULTS: Among the 11
      subjects with moderate hyposmia, carriers of the minor A allele (n = 2) were
      underrepresented (34 carriers among the 70 normosmic subjects; p = 0.049).
      Moreover, carriers of the A allele discriminated odors significantly better than
      non-carriers (13.1+/-1.5 versus 12.3+/-1.6 correct discriminations) and indicated
      a higher intensity of the H2S stimuli (29.2+/-13.2 versus 21+/-12.8 mm VAS, p =
      0.006), which, however, could not be excluded to have involved a trigeminal
      component during stimulation. Finally, the increased sensitivity to thermal pain
      could be reproduced. CONCLUSIONS: The findings are in line with a previous
      association of a human TRPA1 variant with nociceptive parameters and extend the
      association to the perception of odorants. However, this addresses mainly those
      stimulants that involve a trigeminal component whereas a pure olfactory effect
      may remain disputable. Nevertheless, findings suggest that future TRPA1
      modulating drugs may modify the perception of odorants.

PMID- 24752137
TI  - Mutated tumor alleles are expressed according to their DNA frequency.
AB  - The transcription of tumor mutations from DNA into RNA has implications for
      biology, epigenetics and clinical practice. It is not clear if mutations are in
      general transcribed and, if so, at what proportion to the wild-type allele. Here,
      we examined the correlation between DNA mutation allele frequency and RNA
      mutation allele frequency. We sequenced the exome and transcriptome of tumor cell
      lines with large copy number variations, identified heterozygous single
      nucleotide mutations and absolute DNA copy number, and determined the
      corresponding DNA and RNA mutation allele fraction. We found that 99% of the DNA
      mutations in expressed genes are expressed as RNA. Moreover, we found a high
      correlation between the DNA and RNA mutation allele frequency. Exceptions are
      mutations that cause premature termination codons and therefore activate nonsense
      mediated decay. Beyond this, we did not find evidence of any wide-scale
      mechanism, such as allele-specific epigenetic silencing, preferentially promoting
      mutated or wild-type alleles. In conclusion, our data strongly suggest that genes
      are equally transcribed from all alleles, mutated and wild-type, and thus
      transcribed in proportion to their DNA allele frequency. 

PMID- 24752138
TI  - Cytotoxic effect of protoporphyrin IX to human Leukemia U937 cells under
      ultrasonic irradiation.
AB  - BACKGROUND: Sonodynamic therapy (SDT) is an alternative strategy that manages
      malignancies via the generation of cytotoxic factors during ultrasound-activated
      sono-sensitive agents. However, the detailed mechanisms are not clear. This study
      was to identify the cytotoxic effects of ultrasound-activated protoporphyrin IX
      (PpIX) on U937 cells. METHODS: Flow cytometry was performed to detect the time
      course for PpIX uptake in U937 cells. Sub-cellular localization of PpIX in U937
      cells was visualized by inverted confocal laser scanning microscope. Following
      PpIX-mediated SDT treatment, cell viability was evaluated by the 3-(4, 5-
      dimethylthiazol-2-yl)-2, 5-diphenyltetrazoliumbromide (MTT) assay; nuclear damage
      was observed under fluorescent microscope; DNA fragmentation and mitochondrial
      membrane potential disruption were measured by flow cytometry. The role of
      reactive oxygen species (ROS) in SDT-induced cell death was also evaluated.
      RESULTS: We observed that PpIX is mainly localized in the mitochondria, with a
      maximal uptake within 2 h. Compared with PpIX or ultrasound alone, PpIX plus
      ultrasound treatment significantly declined cell viability, caused more serious
      damage of cell morphology, DNA and mitochondria. In the combined treatment group,
      the intracellular ROS was greatly higher than in other groups; ROS scavenger N
      acetylcysteine could effectively rescue the loss of mitochondria membrane
      potential and cell viability induced by SDT. CONCLUSION: Taken together, these
      findings primarily indicated that fatal damage could be induced by PpIX-mediated
      SDT in U937 cells, and the intracellular ROS was involved during this process.
      (c) 2014 S. Karger AG, Basel.

PMID- 24752139
TI  - Stereochemical determination of new cytochalasans from the plant endophytic
      fungus Trichoderma gamsii.
AB  - Three new cytochalasans, trichalasins E (1), F (2) and H (7), together with four
      known analogues, trichalasin C (3), aspochalasin K (4), trichalasin G (5) and
      aspergillin PZ (8), were isolated from one endophytic fungus Trichoderma gamsii
      inhabiting in the traditional medicinal plant Panax notoginseng (BurK.) F.H.
      Chen. Trichalasins E (1) contains a unique hydroperoxyl group, which is the first
      report in all known analogues, whereas trichalasin H (7) possesses the rare
      6/5/6/6/5 pentacyclic skeleton with 12-oxatricyclo [6.3.1.0(2,7)] moiety as that
      of aspergillin PZ (8). The relative configurations of the new compounds were
      characterized by analysis of coupling constants and ROESY correlations, and the
      absolute configurations of trichalasins E (1), H (7) and aspergillin PZ (8) were
      determined by modified Mosher's reaction. In addition, compounds 1-5, 7 and 8
      were tested cytotoxic activities against several cancer cell lines. 

PMID- 24752140
TI  - New cytotoxic diarylheptanoids from the rhizomes of Alpinia officinarum Hance.
AB  - Two new dimeric diarylheptanoids, named Alpinin C (1) and D (2), a new natural
      product of diarylheptanoid (3) along with three known diarylheptanoids (4-6) were
      isolated from the rhizomes of Alpinia officinarum Hance. Their structures were
      elucidated based on extensive spectroscopic analyses (1D and 2D NMR, HRTOFMS,
      IR). The isolated compounds were evaluated for their cytotoxicity against human
      tumor cell lines HepG2, MCF-7, T98G and B16-F10. Compound 1 showed selective
      cytotoxicity against cell lines of MCF-7 and T98G, while compound 6 showed
      significant cytotoxicity to the all tested tumor cell lines with IC50 in the
      range from 8.46 to 22.68 MUmol/L.

PMID- 24752141
TI  - Lycojaponicuminol A-F: cytotoxic serratene triterpenoids from Lycopodium
      japonicum.
AB  - Six new serratene triterpenoids (1-6), together with nine known triterpenoid
      compounds were isolated from the extract of club moss Lycopodium japonicum. The
      structures of isolated compounds were established by spectroscopic methods. The
      cytotoxic activities of all compounds were evaluated against three human cancer
      cell lines in vitro by MTT assay. Compounds 2, 6-8 and 11 exhibited moderate
      activities against all three cell lines with IC50 values of 2.28-11.81 MUg/mL.

PMID- 24752143
TI  - Exserolides A-F, new isocoumarin derivatives from the plant endophytic fungus
      Exserohilum sp.
AB  - Six new isocoumarin derivatives, exserolides A-F (1-6), were isolated from solid
      cultures of the plant endophytic fungus Exserohilum sp., together with four known
      metabolites (7-10). The structures of 1-6 were elucidated primarily by NMR
      experiments. The absolute configuration of the C-3 methine carbon in 1-5 was
      deduced via the circular dichroism data, whereas that of the 1,3-diol moiety in 6
      was assigned from the (1)H NMR data of its (R)- and (S)-MTPA diesters. Compounds
      3 and 9 showed antifungal activity against the plant pathogen Fusarium oxysporum,
      whereas 6 displayed significant inhibitory effects against a small panel of
      bacteria. 

PMID- 24752142
TI  - Bioactive sesquiterpene polyol esters from the leaves of Tripterygium wilfordii.
AB  - Tripterygium wilfordii, a member of Celastraceae family, has been used as a
      traditional plant insecticide and a medicinal plant. Phytochemical investigation
      of the leaves of T. wilfordii has resulted in the isolation of eight
      sesquiterpene polyol esters triptersinines M-T (1-8) and one sesquiterpene
      pyridine alkaloid (9). The structures of the compounds were elucidated on the
      basis of spectroscopic data analyses, including UV, IR, MS, and NMR experiments.
      The inhibitory effects on nitric oxide production in LPS-induced macrophages of 1
      9 were also evaluated. 

PMID- 24752144
TI  - Modulation of pilocarpine-induced seizures by cannabinoid receptor 1.
AB  - Administration of the muscarinic agonist pilocarpine is commonly used to induce
      seizures in rodents for the study of epilepsy. Activation of muscarinic receptors
      has been previously shown to increase the production of endocannabinoids in the
      brain. Endocannabinoids act at the cannabinoid CB1 receptors to reduce
      neurotransmitter release and the severity of seizures in several models of
      epilepsy. In this study, we determined the effect of CB1 receptor activity on the
      induction in mice of seizures by pilocarpine. We found that decreased activation
      of the CB1 receptor, either through genetic deletion of the receptor or treatment
      with a CB1 antagonist, increased pilocarpine seizure severity without modifying
      seizure-induced cell proliferation and cell death. These results indicate that
      endocannabinoids act at the CB1 receptor to modulate the severity of pilocarpine
      induced seizures. Administration of a CB1 agonist produced characteristic CB1
      dependent behavioral responses, but did not affect pilocarpine seizure severity.
      A possible explanation for the lack of effect of CB1 agonist administration on
      pilocarpine seizures, despite the effects of CB1 antagonist administration and
      CB1 gene deletion, is that muscarinic receptor-stimulated endocannabinoid
      production is acting maximally at CB1 receptors to modulate sensitivity to
      pilocarpine seizures. 

PMID- 24752145
TI  - Zinc oxide inverse opal electrodes modified by glucose oxidase for
      electrochemical and photoelectrochemical biosensor.
AB  - The ZnO inverse opal photonic crystals (IOPCs) were synthesized by the sol-gel
      method using the polymethylmethacrylate (PMMA) as a template. For glucose
      detection, glucose oxidase (GOD) was further immobilized on the inwall and
      surface of the IOPCs. The biosensing properties toward glucose of the
      Nafion/GOD/ZnO IOPCs modified FTO electrodes were carefully studied and the
      results indicated that the sensitivity of ZnO IOPCs modified electrode was 18
      times than reference electrode due to the large surface area and uniform porous
      structure of ZnO IOPCs. Moreover, photoelectrochemical detection for glucose
      using the electrode was realized and the sensitivity approached to 52.4 uA mM(-1)
      cm(-2), which was about four times to electrochemical detection (14.1 uA mM(-1)
      cm(-2)). It indicated that photoelectrochemical detection can highly improve the
      sensor performance than conventional electrochemical method. It also exhibited an
      excellent anti-interference property and a good stability at the same time. This
      work provides a promising approach for realizing excellent photoelectrochemical
      biosensor of similar semiconductor photoelectric material.

PMID- 24752146
TI  - Genetically-encoded nanosensor for quantitative monitoring of methionine in
      bacterial and yeast cells.
AB  - Metabolic engineering of microorganisms for production of biological molecules
      represent a key goal for industrial biotechnology. The metabolic engineering
      requires detailed knowledge of the concentrations and flux rates of metabolites
      and metabolic intermediates in vivo. Genetically-encoded fluorescence resonance
      energy transfer (FRET) sensors represent a promising technology for measuring
      metabolite levels and corresponding rate changes in live cells. In the present
      paper, we report the development of genetically-encoded FRET-based nanosensor for
      methionine as metabolic engineering of microbial strains for the production of l
      methionine is of major interest in industrial biotechnology. In this nanosensor,
      methionine binding protein (MetN) from Escherichia coli (E. coli) K12 was taken
      and used as the reporter element of the sensor. The MetN was sandwiched between
      cyan fluorescent protein (CFP) and yellow fluorescent protein (YFP). Specificity,
      affinity, pH stability and metal effects was analyzed for the in vitro
      characterization of this nanosensor, named as FLIPM. The FLIPM is very specific
      to methionine and found to be stable with the pH within the physiological range.
      The calculated affinity (Kd) of FLIPM was 203 uM. This nanosensor successfully
      monitored the intracellular level of methionine in bacterial as well as yeast
      cell. The data suggest that these nanosensors may be a versatile tool for
      studying the in vivo dynamics of methionine level non-invasively in living cells.

PMID- 24752147
TI  - A label-free electrochemical DNA sensor using methylene blue as redox indicator
      based on an exonuclease III-aided target recycling strategy.
AB  - In this work, using methylene blue (MB) as a redox marker and exonuclease III
      (Exo III) as an amplificatory enzyme, we developed a facile and a label-free
      electrochemical method for sensitive DNA detection. A double-stranded DNA (dsDNA)
      probe was prepared by hybridizing two single-stranded DNA (ssDNA) probes. In the
      ssDNA probes, one ssDNA was guanine bases free and the other one consisted of
      many unbound guanine bases. MB could be absorbed on the unbound guanine bases
      owing to the specific interaction between MB and the guanine bases. When the
      dsDNA probe was challenged with target DNA, it induced a simple Exo III assisted
      cleavage process, accompanied by the release of the unbound guanine bases. Thus,
      the amount of MB absorbed on the electrode was much less compared to the initial
      signal. The detection limit for DNA was found to be as low as 20 fM. Moreover, it
      could discriminate mismatched DNA from perfectly matched target DNA. This
      detection method is simple in design, fast in operation and can be applied to
      detect different DNA sequences.

PMID- 24752148
TI  - Selective and sensitive detection of free bilirubin in blood serum using human
      serum albumin stabilized gold nanoclusters as fluorometric and colorimetric
      probe.
AB  - We report here a fluorescence quenching based non-enzymatic method for sensitive
      and reliable detection of free bilirubin in blood serum samples using human serum
      albumin (HSA) stabilized gold nanoclusters (HSA-AuNCs) as fluorescent probe. The
      fluorescence of the nanoclusters was strongly quenched by bilirubin in a
      concentration dependent manner by virtue of the inherent specific interaction
      between bilirubin and HSA. A strong binding constant of 0.55*10(6) L mole(-1)
      between the HSA-AuNC and bilirubin was discerned. The nano clusters each with
      size ~1.0 nm (in diameter) and a core of Au18 were homogeneously distributed in
      HSA molecules as revealed from the respective high resolution transmission
      electron microscopic and mass spectroscopic studies. The fluorescence quenching
      phenomena which obeyed a simple static quenching mechanism, was utilized for
      interference free detection of bilirubin with minimum detection limit (DL) of
      248+/-12 nM (S/N=3). The fluorescence response of HSA-AuNCs against bilirubin was
      practically unaltered over a wide pH (6-9) and temperature (25-50  degrees C)
      range. Additionally, peroxidase-like catalytic activity of these nanoclusters was
      exploited for colorimetric detection of bilirubin in serum sample with a DL of
      200+/-19 nM by following the decrease in absorbance (at lambda440 nm) of the
      reaction and its rate constant (Kp) of 2.57+/-0.63 mL MUg(-1) min(-1). Both these
      fluorometric and colorimetric methods have been successfully used for detection
      of free bilirubin in blood serum samples.

PMID- 24752149
TI  - Ultrasensitive enzyme-free electrochemical immunoassay for free thyroxine based
      on three dimensionally ordered macroporous chitosan-Au nanoparticles hybrid film.
AB  - The measurement of free thyroxine concentration in serum is considered to be an
      essential indicator of thyroid function. Here, a novel enzyme-free sandwich
      electrochemical immunosensor for the detection of FT4 antigen based on the
      immobilization of primary antibody (Ab1) on three dimensional ordered macroporous
      chitosan-Au nanoparticles hybrid (3DOM CS-AuNPs) film electrode, and magnetic
      multiwall carbon nanotubes (MMWCNTs) were used as label of secondary antibody
      (Ab2). The 3DOM CS-AuNPs film electrode was constructed by one-step
      electrodeposition of CS-AuNPs composite onto Au electrode with silica opal
      template. MMWCNTs were prepared by chemical co-precipitation of Fe(2+) and Fe(3+)
      salts on carboxylated MWCNTs. Ru(bpy)3(2+) labeled anti-FT4 (Ru(bpy)3(2+)-Ab2)
      was covalently attached to MMWCNTs through the formation of amide bond between
      the carboxylic groups of MWCNTs and the amine groups of antibody. Under the
      optimal conditions, FT4 was detected in a concentration range from 0.71 fg mL(-1)
      to 1.15 pg mL(-1) with a correlation coefficient of 0.998 and a detection limit
      of 0.20 fg mL(-1). Moreover, the immunosensor showed excellent selectivity, good
      stability, satisfactory reproducibility and regeneration. Importantly, the
      developed method was used to assay clinical serum specimens, achieving a good
      relation with those obtained from the commercialized electrochemiluminescent
      method.

PMID- 24752150
TI  - High-salt diet enhances hippocampal oxidative stress and cognitive impairment in
      mice.
AB  - Previous evidence suggests that a high-salt (HS) diet may increase oxidative
      stress and contribute to the development of hypertension that is already present.
      Oxidative stress is thought to play a critical role in the development of
      neurodegenerative diseases. Lower dietary sodium intake putatively contributes to
      a lower rate of cognitive impairment; however, the specific effects of HS diet on
      cognitive function remain poorly understood. In this work, C57BL/6J mice were
      administered a normal-salt (NS) diet (0.4% NaCl) or a HS diet (7.0% NaCl) for 12
      weeks, and cognitive ability and oxidative stress in the brain were measured. It
      was found that the HS diet significantly impaired retention of spatial memory.
      Additionally, superoxide anion production in the hippocampus was significantly
      increased in the HS diet mice compared with that in the NS mice. Interestingly,
      the antioxidant defense capacities for HS diet mice were markedly reduced in the
      hippocampus, but not in the cerebral cortex, compared with the NS mice. Taken
      together, these data demonstrate that HS diet directly impairs retention of
      spatial memory, which may be related to the increased oxidative stress observed
      in the hippocampus.

PMID- 24752151
TI  - cGMP-dependent protein kinase type II knockout mice exhibit working memory
      impairments, decreased repetitive behavior, and increased anxiety-like traits.
AB  - Neuronal activity regulates AMPA receptor trafficking, a process that mediates
      changes in synaptic strength, a key component of learning and memory. This form
      of plasticity may be induced by stimulation of the NMDA receptor which, among its
      activities, increases cyclic guanosine monophosphate (cGMP) through the nitric
      oxide synthase pathway. cGMP-dependent protein kinase type II (cGKII) is
      ultimately activated via this mechanism and AMPA receptor subunit GluA1 is
      phosphorylated at serine 845. This phosphorylation contributes to the delivery of
      GluA1 to the synapse, a step that increases synaptic strength. Previous studies
      have shown that cGKII-deficient mice display striking spatial learning deficits
      in the Morris Water Maze compared to wild-type littermates as well as lowered
      GluA1 phosphorylation in the postsynaptic density of the prefrontal cortex
      (Serulle et al., 2007; Wincott et al., 2013). In the current study, we show that
      cGKII knockout mice exhibit impaired working memory as determined using the
      prefrontal cortex-dependent Radial Arm Maze (RAM). Additionally, we report
      reduced repetitive behavior in the Marble Burying task (MB), and heightened
      anxiety-like traits in the Novelty Suppressed Feeding Test (NSFT). These data
      suggest that cGKII may play a role in the integration of information that conveys
      both anxiety-provoking stimuli as well as the spatial and environmental cues that
      facilitate functional memory processes and appropriate behavioral response. 

PMID- 24752153
TI  - Stress and the regulation of memory: from basic mechanisms to clinical
      implications Neurobiology of Learning and Memory Special Issue.

PMID- 24752152
TI  - Covert rapid action-memory simulation (CRAMS): a hypothesis of hippocampal
      prefrontal interactions for adaptive behavior.
AB  - Effective choices generally require memory, yet little is known regarding the
      cognitive or neural mechanisms that allow memory to influence choices. We outline
      a new framework proposing that covert memory processing of hippocampus interacts
      with action-generation processing of prefrontal cortex in order to arrive at
      optimal, memory-guided choices. Covert, rapid action-memory simulation (CRAMS) is
      proposed here as a framework for understanding cognitive and/or behavioral
      choices, whereby prefrontal-hippocampal interactions quickly provide multiple
      simulations of potential outcomes used to evaluate the set of possible choices.
      We hypothesize that this CRAMS process is automatic, obligatory, and covert,
      meaning that many cycles of action-memory simulation occur in response to choice
      conflict without an individual's necessary intention and generally without
      awareness of the simulations, leading to adaptive behavior with little perceived
      effort. CRAMS is thus distinct from influential proposals that adaptive memory
      based behavior in humans requires consciously experienced memory-based
      construction of possible future scenarios and deliberate decisions among possible
      future constructions. CRAMS provides an account of why hippocampus has been shown
      to make critical contributions to the short-term control of behavior, and it
      motivates several new experimental approaches and hypotheses that could be used
      to better understand the ubiquitous role of prefrontal-hippocampal interactions
      in situations that require adaptively using memory to guide choices. Importantly,
      this framework provides a perspective that allows for testing decision-making
      mechanisms in a manner that translates well across human and nonhuman animal
      model systems. 

PMID- 24752155
TI  - Assessing the learning curve for totally laparoscopic major-complex liver
      resections: a single hepatobiliary surgeon experience.
AB  - BACKGROUND: Encouraging results have been reported in terms of feasibility,
      safety, and oncologic, outcomes even for major (>= 3 segments) or complex for
      location-specific (right posterior segments) laparoscopic liver resections.
      Despite this, technically challenging issues and advanced laparoscopic skills
      required to perform it have limited its use in few highly specialized centers.
      The aim of this study was to assess the learning curve for major-complex totally
      laparoscopic liver resections (TLLR) performed by a single HPB surgeon. MATERIALS
      AND METHODS: From October 2008 to February 2012, a total of 70 TLLR were
      performed; 24 (33.3%) were major-complex resections. This series was divided in 2
      groups according to time of operation: group A (12 cases early series) and group
      B (12 cases late series); perioperative outcomes were retrospectively analyzed
      and compared. RESULTS: Comparing the 2 groups, a statistically significant
      improvement was found in terms of operative time (P=0.017), blood loss (P=0.004),
      number of cases requiring a Pringle maneuver (P=0.006), and blood transfusion
      (P=0.001) from case number ten onward. CONCLUSIONS: This study shows that a
      minimum of 10 cases are required to obtain a significant improvement in
      perioperative outcome for surgeons with specific training on hepatobiliary
      surgery and advanced laparoscopic surgical procedures. More studies are required
      to clarify the minimum standard of training to perform safely this kind of
      advanced laparoscopic liver surgery on a large scale.

PMID- 24752156
TI  - Male sexual function after total mesorectal excision: a comparison between
      laparoscopic and open surgery during the learning curve period.
AB  - INTRODUCTION: This study assessed male sexual function using a specific and
      validated questionnaire, the International Index of Erectile Function (IIEF), in
      patients subjected to open total mesorectal excision (OTME) and laparoscopic
      total mesorectal excision (LTME) and compared it with a control group. PATIENTS
      AND METHODS: The inclusion criteria consisted of male patients with an active
      sexual life before surgery subjected to OTME or LTME at the Coloproctological
      Unit of the Clinics Hospital, Minas Gerais Federal University, between January
      2005 and September 2009. The IIEF questionnaire was used. The control group
      comprised 30 randomly selected men (older than 35 y of age) without previous
      pelvic or abdominal surgery and without any genitourinary complaints. RESULTS:
      Between January 2005 and September 2009, 77 male patients were subjected to total
      mesorectal excision, with 26 meeting the inclusion criteria and answering the
      questionnaire: 13 in the OTME group and 13 in the LTME group. When the 3 groups
      were compared in each IIEF domain, there were significant differences in erectile
      function (P=0.05), orgasm and ejaculation (P=0.009), sexual intercourse
      satisfaction (P=0.01), and overall satisfaction (P=0.025), favoring the LTME and
      control groups. No difference was found in sexual desire (P=0.285). CONCLUSIONS:
      LTME may have the benefit of preserving male sexual function compared with OTME,
      even in the learning curve period.

PMID- 24752154
TI  - A comparison of the rest complex binding patterns in embryonic stem cells and
      epiblast stem cells.
AB  - We detected and characterized the binding sites of the representative Rest
      complex components Rest, Sin3A, and Lsd1. We compared their binding patterns in
      mouse embryonic stem (ES) cells and epiblast stem (EpiS) cells. We found few Rest
      sites unique to the EpiS cells. The ES-unique site features were distinct from
      those of the common sites, namely, the signal intensities were weaker, and the
      characteristic gene function categories differed. Our analyses showed that the
      Rest binding sites do not always overlap with the Sin3A and Lsd1 binding sites.
      The Sin3A binding pattern differed remarkably between the ES and EpiS cells and
      was accompanied by significant changes in acetylated-histone patterns in the
      surrounding regions. A series of transcriptome analyses in the same cell types
      unexpectedly showed that the putative target gene transcript levels were not
      dramatically different despite dynamic changes in the Rest complex binding
      patterns and chromatin statuses, which suggests that Rest is not the sole
      determinant of repression at its targets. Nevertheless, we identified putative
      Rest targets with explicitly enhanced transcription upon Rest knock-down in 143
      and 60 common and ES-unique Rest target genes, respectively. Among such sites,
      several genes are involved in ES cell proliferation. In addition, we also found
      that long, intergenic non-coding RNAs were apparent Rest targets and shared
      similar features with the protein-coding target genes. Interestingly, such non
      coding target genes showed less conservation through evolution than protein
      coding targets. As a result of differences in the components and targets of the
      Rest complex, its functional roles may differ in ES and EpiS cells. 

PMID- 24752157
TI  - Modified laparoscopic technique for fixation of peritoneal dialysis catheter.
AB  - BACKGROUND: Continuous ambulatory peritoneal dialysis (CAPD) is a treatment for
      patients with end-stage renal disease (ESRD). Peritoneal dialysis catheters are
      usually placed using a small laparotomy. This traditional technique is usually
      safe if well executed, but it cannot be safely performed if the patient has had a
      previous abdominal operation. A minimally invasive procedure may progress safely
      by laparoscopic intervention. However, dysfunction of the catheter during a
      laparoscopic intervention is a common complication related to CAPD. This usually
      involves intra-abdominal migration of the catheter, even with one intra-abdominal
      fixation. In an effort to increase catheter survival, we tested a modified
      laparoscopic technique with two intra-abdominal fixations of a Tenckhoff
      catheter. MATERIALS AND METHODS: Forty-one consecutive ESRD patients (mean age,
      53.4 y; range, 31 to 84 y) underwent modified laparoscopic Tenckhoff catheter
      implantation with 2 intra-abdominal fixations between September 2009 and January
      2013. The same perioperative protocol and surgical technique were used in all
      patients. Another 49 ESRD patients who had received laparoscopic Tenckhoff
      catheter implantation with 1 intra-abdominal fixation performed by the same
      surgeon were retrospectively recruited for comparison. RESULTS: The modified
      laparoscopic procedure with two intra-abdominal fixations of a Tenckhoff catheter
      was successfully performed in all patients. The mean operating time was 24.3
      minutes (range, 15 to 37 min). The mean blood loss was 5.6 mL (range, 5 to 20
      mL). Catheter survival was 100% until February 2013. No major perioperative
      complications were found. A Kaplan-Meier Survival Analysis found no significant
      difference between the 2 groups in sex, age, operative time, or blood loss. The
      catheter survival rate was significantly higher in the patients with two intra
      abdominal fixations. Most patients were satisfied with the functional results of
      the Tenckhoff catheter. CONCLUSIONS: The laparoscopic 2-site fixation technique
      is an effective and safe procedure but long-term follow-up and more cases are
      necessary.

PMID- 24752158
TI  - Postoperative respiratory complications and peak airway pressure during
      laparoscopic colectomy in patients with colorectal cancer.
AB  - To determine whether the incidence of postoperative pulmonary complications
      increases in patients with high peak airway pressure (>=30 cm H2O) during
      laparoscopic colectomy, we investigated consecutive patients with colorectal
      cancer who had undergone laparoscopic colectomy. Of the 115 enrolled patients, 34
      patients (30%) had peak airway pressure >=30 cm H2O (an overload group). Compared
      with a nonoverload group (peak airway pressure <30 cm H2O), the overload group
      had a 5-fold greater incidence of postoperative respiratory complications and
      operations of longer duration, longer postanesthesia care unit stays, greater
      alveolar-arterial O2 differences, greater alveolar dead space-to-tidal volume
      ratios, and lower PaO2 measurements. Body mass index and preoperative alveolar
      arterial O2 difference significantly affect higher peak airway pressure occurring
      during laparoscopic colectomy. Patients who had peak airway pressures >=30 cm H2O
      during laparoscopic colectomy for colorectal cancer had higher incidence of
      postoperative respiratory complications than those whose peak airway pressures
      remained <30 cm H2O. 

PMID- 24752159
TI  - Surgical strategy for the gastric gastrointestinal stromal tumors (GISTs) larger
      than 5 cm: laparoscopic surgery is feasible, safe, and oncologically acceptable.
AB  - BACKGROUND: The efficacy and feasibility of laparoscopic surgery (LAP) for
      gastric GISTs >5 cm has not been adequately assessed. Here we investigated the
      clinical outcomes of these patients. PATIENTS AND METHODS: Twenty-seven
      consecutive patients who underwent resection for gastric GISTs >5 cm were
      enrolled in this retrospective study. We assessed the tumor characteristics,
      surgical outcomes, tumor recurrence, and patient survival in the open surgery
      (OPEN) group and in the LAP group. RESULTS: The tumor size in the OPEN group was
      larger than that in the LAP group, but there were no differences in the mitotic
      count. There were no differences in operative complications. Finally, there were
      no differences in the disease-free and no patients in the LAP group died.
      CONCLUSIONS: In patients with gastric GISTs >5 cm, LAP can be performed with
      outcomes equivalent to those of OPEN if patient selection and intraoperative
      judgment are appropriate.

PMID- 24752160
TI  - Comparison of stapling techniques and management of the mesoappendix in
      laparoscopic appendectomy.
AB  - Many techniques for laparoscopic appendectomy have been proposed with few
      comparative studies. We performed a retrospective review of all patients
      undergoing laparoscopic appendectomy for uncomplicated appendicitis from 2006 to
      2011. Techniques were: (1) transection of the mesoappendix and appendix with a
      single staple line (SSL); (2) transection of the mesoappendix and appendix with
      multiple staple lines (MSL); and (3) transection of the mesoappendix with
      ultrasonic shears and the appendix with a single staple line (USSL). A total of
      565 cases were reviewed (149 SSL, 259 MSL, and 157 USSL). Patients treated with
      the SSL technique had decreased operative duration (P<0.001) and length of stay
      (P=0.003) despite equivalent disease presentations. Multivariate analysis
      demonstrated decreased operative duration with the SSL technique (P=0.001). Use
      of a SSL for transection of the mesoappendix and appendix is both a safe and
      efficient technique that results in reduced operative duration with excellent
      surgical outcomes. 

PMID- 24752161
TI  - Management of staple line leaks after sleeve gastrectomy in a consecutive series
      of 378 patients.
AB  - INTRODUCTION: Laparoscopic sleeve gastrectomy (LSG) is gaining acceptance as a
      stand-alone bariatric procedure with proven efficacy on weight loss and obesity
      related comorbidities. A specific and potentially severe complication of LSG is
      the staple line leak (SLL). Our aim was to report the SLL rate and its management
      in a prospective cohort of 378 LSGs. PATIENTS AND METHODS: A total of 378
      patients underwent LSG from July 2005 to July 2011. The gastric transection was
      performed by an initial 60 mm firing of 4.5 mm staples at the antrum and
      successive 60 mm firings of 3.5 mm staples at the gastric body and fundus toward
      the left diaphragmatic crus. A 36 Fr bougie was used to calibrate the gastric
      tube. The staple line was systematically reinforced with a partial-thickness
      running suture. RESULTS: The overall complications and SLL rate were 20/378
      (5.29%) and 9/378 (2.38%), respectively. SLLs were managed by laparoscopic (n=2)
      or open (n=1) exploration, drainage and endoscopic self-expandable covered stent,
      computed tomography-guided percutaneous drainage (n=2), or a self-expandable
      covered stent alone (n=4). Medical support including total parenteral nutrition
      and adapted antibiotics was started in all patients. The combined treatment
      modalities were successful in all cases. CONCLUSIONS: SLL was the most common
      complication of LSG accounting for half of the overall complications.
      Percutaneous drainage and self-covered stents combined with antibiotics and
      parenteral nutrition are effective for SLL and should be proposed as first-line
      treatment in stable patients.

PMID- 24752162
TI  - The effects of different oxygen concentrations on recruitment maneuver during
      general anesthesia for laparoscopic surgery.
AB  - INTRODUCTION AND PURPOSE: Recruitment maneuvers (RMs), which aim to ventilate the
      collaborated alveolus by temporarily increasing the transpulmonary pressure, have
      positive effects in relation to respiration, mainly oxygenation. Although many
      studies have defined the pressure values used during RM and the application
      period, our knowledge of the effects of different oxygen concentrations is
      limited. In this study, we aimed to determine the effects of different oxygen
      concentrations during RM on the arterial oxygenation and respiration mechanics in
      laparoscopic cases. MATERIALS AND METHODS: Thirty-two patients undergoing
      laparoscopic cholecystectomy were recruited into the study. The patients were
      randomly divided into 2 groups. RM with a 30% oxygen concentration was performed
      in patients within the first group (group I, n=16), whereas patients in the
      second group (group II, n=16) received RM with 100% oxygen. To study respiratory
      mechanics, dynamic compliance (Cdyn), airway resistance (Raw), and peak
      inspiratory pressure were measured at 3 different times: 5 minutes after
      anesthesia induction, 5 minutes after the abdomen was insufflated, and 5 minutes
      after the abdomen was desufflated. Arterial blood gases were measured during
      surgery and 30 minutes after surgery (postoperative). RESULTS: The average
      postoperative partial arterial oxygen pressure values of the patients in groups I
      and II were 121 and 98 mm Hg, respectively. The difference between the groups was
      statistically significant. In addition, the decrease in compliance from induction
      values after desufflation in group II was statistically significant. DISCUSSION:
      On the basis of our results, maintaining oxygen concentrations below 100% during
      RM may be more beneficial in terms of respiratory mechanics and gas exchange.

PMID- 24752163
TI  - A cadaver lab training facility to facilitate laparoscopic liver resection.
AB  - INTRODUCTION: Laparoscopic liver surgery is becoming increasingly common;
      however, doubts still remain regarding its more widespread application and
      whether it improves patient outcome. The authors would like to present their
      experience of using a dedicated cadaver laparoscopic training laboratory to
      facilitate the introduction of a laparoscopic liver resection (LLR) program.
      METHODS: A course was designed by a faculty of experienced, advanced laparoscopic
      surgeons providing an intensive 2-day course of lectures, debate, exchange, and
      practical hands-on with a live link to clinical LLR operations. Participant
      evaluation and feedback for each course was analyzed. RESULTS: After 4 courses
      (2007 to 2009) and 32 participants, scores were graded from 1 (poor) to 6
      (excellent no improvement). The course was graded for content, structure,
      delivery, resources, facility, and value for money. The overall rating for
      cadaver teaching sessions scored as follows: score 6 (43%), score 5 (32%), and
      score 4 (25%). CONCLUSIONS: A dedicated cadaver LLR facility is not only an
      excellent method to train individuals for safe introduction of clinical liver
      resection program but it also has the potential to provide certification within
      this growing technique.

PMID- 24752164
TI  - Open-access technique and "critical view of safety" as the safest way to perform
      laparoscopic cholecystectomy.
AB  - BACKGROUND: The 2 main challenges of laparoscopic cholecystectomy are primary
      peritoneal access and safe identification, ligation, and division of the cystic
      duct and cystic artery. PATIENTS AND METHODS: This is a 13-year period
      retrospective study from January 2000 to December 2012. All the operations were
      performed by 1 surgeon and all the data were collected from the hospitals
      archive. A total of 929 laparoscopic cholecystectomies were performed for
      symptomatic cholelithiasis. The first author was involved in all the operations
      either by performing or assisting in them. The open access (OA) technique was
      used in all cases for the creation of pneumoperitoneum. After establishing the
      pneumoperitoneum, the "critical view of safety" (CVS) technique was used to
      ligate and divide the cystic duct and cystic artery. When the OA was not possible
      or CVS was not feasible, the operation was converted to open. RESULTS: Successful
      establishment of pneumoperitoneum with OA was possible in 911 of 929 (98.06%)
      patients and CVS was achieved in 873 patients (95.82%). In 18 patients the
      operation was converted to open because of dense adhesions not permitting the
      establishment of the pneumoperitoneum. No intraoperative or postoperative
      complications occurred in these patients. No bile duct injury occurred in this
      series. Postoperative complications were recorded in 19 patients (2.04%). Five
      patients had bleeding from port sites, 12 patients had wound infection at the
      umbilical incision, and 2 patients developed subhepatic collections, which were
      drained percutaneously under computed tomographic guidance. CONCLUSIONS: In this
      series of laparoscopic cholecystectomies, we used the "open access" technique to
      create pneumoperitoneum and we obtained the "critical view of safety" for the
      identification of the cystic duct. Our results show that this approach is the
      safest way to perform and teach laparoscopic cholecystectomy.

PMID- 24752165
TI  - Sugammadex reduces postoperative pain after laparoscopic bariatric surgery: a
      randomized trial.
AB  - BACKGROUND: Morbid obese (MO) population is increasing every year worldwide, and
      laparoscopic bariatric surgery (LBS) has a central role in their treatment. The
      postoperative period of MO is not free from complications. The introduction of
      sugammadex has brought huge developments in patient's safety and nowadays LBS is
      performed with better care and quality. However, the effect of this agent in
      postoperative pain is still unknown. MATERIALS AND METHODS: A controlled trial
      enrolling 88 MO submitted to LBS under general anesthesia using muscle
      relaxation, randomly assigned into 2 groups: one received sugammadex (SUG group)
      at the end of surgery and the other neostigmine (NEO group). In the
      postanesthetic care unit (PACU), we evaluated pain using the visual analogue
      scale in 4 different moments: arrival in the PACU, 30 minutes after arrival, 60
      minutes after arrival, and immediately before leaving the PACU. We also recorded
      the presence of postoperative nausea and vomits (PONV) and the duration of the
      PACU stay before discharge to the ward. RESULTS: Forty-four patients received
      sugammadex and 44 received neostigmine. We found lower visual analogue scale pain
      scores in the SUG group at 30 and 60 minutes after arriving to the PACU (P<0.05).
      We also had less PONV in the SUG group and these patients were also discharged
      earlier. CONCLUSIONS: Sugammadex is associated with less pain felt in the PACU.
      This "opioid-sparing" effect, combined with less PONV and a faster discharge from
      the PACU, makes sugammadex an indispensable drug in this type of patients and
      allows fast-track surgery in the MO.

PMID- 24752166
TI  - The superficial precoagulation, sealing, and transection method: a "bloodless"
      and "ecofriendly" laparoscopic liver transection technique.
AB  - BACKGROUND: Minimizing blood loss is an important aspect of laparoscopic liver
      resection. Liver transection is the most challenging part of liver resection, but
      no standard method is available for this step at present. Herein, we have
      introduced the superficial precoagulation, sealing, and transection (SPST)
      method, a potentially "bloodless" and "ecofriendly" laparoscopic liver
      transection technique involving reusable devices: the VIO soft-coagulation
      system; VIO BiClamp (bipolar electrosurgical coagulation); Olympus SonoSurg
      (ultrasonic surgical system); and CUSA (ultrasonic aspirator). Furthermore, we
      have reported the short-term outcomes of laparoscopic liver transection with the
      SPST method. METHODS: The study included 14 consecutive patients who underwent
      laparoscopic partial liver resection with the SPST method at a single institution
      between August 2008 and June 2010. RESULTS: The median operative time was 201
      minutes (range, 97 to 332 min) and the median blood loss was 5 mL (range, 5 to
      250 mL). There was no requirement for blood transfusion, no intraoperative
      complications, and no cases of conversion to open laparotomy. There were no liver
      transection-related complications such as postoperative bile leakage, bleeding,
      or infection. All surgical margins were negative, with a mean margin of 4.6 mm,
      and no local recurrence was observed at an average follow-up of 37.6 months.
      CONCLUSIONS: The SPST method is a simple, efficient, and cost-effective surgical
      technique for laparoscopic liver resection. It is associated with low
      intraoperative blood loss and good short-term outcomes. We recommend that the
      SPST method should be used as a standard technique for laparoscopic liver
      transection (Supplemental Digital Content 1, http://links.lww.com/SLE/A103).

PMID- 24752167
TI  - Laparoscopic management of infected mesh after laparoscopic inguinal hernia
      repair.
AB  - PURPOSE: We present our experience with 10 patients with infected meshes after
      laparoscopic inguinal hernia repair in whom we explanted infected meshes
      laparoscopically. METHODS: On retrospective analysis over 5 years (2007 to 2012),
      we identified 10 patients (6 TAPP/4 TEP) with localized deep-seated mesh
      infections in whom infected meshes were explanted laparoscopically. Peritoneum
      was incised, associated abscesses were drained, meshes were identified,
      separated, and extracted through 10/12 mm port. RESULTS: Nine patients
      experienced resolution of symptoms after 3 weeks of surgical intervention and
      remained asymptomatic at mean follow-up of 20 months (range, 4 to 42 mo). One
      patient with recurrent abscess required surgical drainage twice. Mean hospital
      stay was 2.2 days (range, 1 to 9 d). Two patients developed recurrent hernia at 6
      and 8 months after mesh explantation. CONCLUSIONS: Laparoscopic explantation of
      infected meshes after laparoscopic hernia repair leads to less scarring and early
      recovery. Contamination of anterior abdominal wall after cutaneous drainage of
      deep-seated abscess is avoided.

PMID- 24752168
TI  - The effect of serosal suture reinforcement on burst pressure in sleeve
      gastrectomy specimens.
AB  - PURPOSE: Staple-line leak is a life-threatening complication of laparoscopic
      sleeve gastrectomy. Reinforcement materials have been reported to lower the risk
      of staple-line bleeding, but their effects on leak risk have not been elucidated.
      The aim of this study was to compare the effects of 2 supportive techniques on
      burst pressures in sleeved gastrectomy specimens. METHODS: A total of 30 patients
      who underwent laparoscopic sleeve gastrectomy were evaluated. The resected sleeve
      gastrectomy specimens were categorized into 3 groups: group 1 had no extra
      support in the staple-line, group 2 had interrupted serosal suture on the staple
      line, and group 3 had serosal suture on staple-line junction points. The endpoint
      was the first detectable leakage, at which point the leak pressure and anatomic
      site of the leakage were recorded. RESULTS: A total of 30 sleeved gastrectomy
      specimens were included (each group included 10 specimens). There were no
      differences between groups in terms of age, sex, and body mass index. The leak
      pressure was significantly higher (56.2+/-6.4 mm Hg) in group 2 (P<0.01). Leaks
      occurred significantly more frequently in the staple-line than in the staple-line
      junction points (P<0.01). CONCLUSIONS: Interrupted serosal suture significantly
      increased the burst pressure. Increases in intraluminal pressure are known to be
      significant in leak etiology. Thus, we concluded that interrupted serosal suture
      may be beneficial in the prevention of leaks.

PMID- 24752169
TI  - Verres needle desufflation as an effective treatment option for colonic
      perforation after colonoscopy.
AB  - BACKGROUND: This study aimed to assess the incidence of colonoscopic perforation
      and the efficacy of minimal invasive management by Verres needle desufflation.
      MATERIALS AND METHODS: All colonoscopies performed between January 2007 and
      January 2012, at the Maastricht University Medical Centre, were reviewed.
      RESULTS: During the study period, 18,449 colonoscopies were performed. Fourteen
      colonoscopic perforations were diagnosed. Seven patients underwent immediate
      surgery, whereas the remaining 7 patients were initially managed conservatively:
      5 of these patients also underwent Verres needle desufflation. One of the
      patients who received Verres needle desufflation underwent secondary surgery
      because of failure of nonsurgical treatment. Conservative management of
      colonoscopic perforation, including treatment with Verres needle desufflation,
      was associated with lower complication rates and shorter hospital stays compared
      with immediate surgical intervention. CONCLUSIONS: Verres needle desufflation in
      combination with nil per os and antibiotic treatment is a safe option for
      managing colon perforation after colonoscopy in selected patients lacking
      clinical signs of peritonitis or sepsis.

PMID- 24752170
TI  - Inhibition of Paracoccidioides lutzii Pb01 isocitrate lyase by the natural
      compound argentilactone and its semi-synthetic derivatives.
AB  - The dimorphic fungus Paracoccidioides spp. is responsible for
      paracoccidioidomycosis, the most prevalent systemic mycosis in Latin America,
      causing serious public health problems. Adequate treatment of mycotic infections
      is difficult, since fungi are eukaryotic organisms with a structure and
      metabolism similar to those of eukaryotic hosts. In this way, specific fungus
      targets have become important to search of new antifungal compound. The role of
      the glyoxylate cycle and its enzymes in microbial virulence has been reported in
      many fungal pathogens, including Paracoccidioides spp. Here, we show the action
      of argentilactone and its semi-synthetic derivative reduced argentilactone on
      recombinant and native isocitrate lyase from Paracoccidioides lutzii Pb01 (PbICL)
      in the presence of different carbon sources, acetate and glucose. Additionally,
      argentilactone and its semi-synthetic derivative reduced argentilactone exhibited
      relevant inhibitory activity against P. lutzii Pb01 yeast cells and dose
      dependently influenced the transition from the mycelium to yeast phase. The other
      oxygenated derivatives tested, epoxy argentilactone and diol argentilactone-, did
      not show inhibitory action on the fungus. The results were supported by in silico
      experiments. 

PMID- 24752174
TI  - A cascade signal amplification strategy for sensitive and label-free DNA
      detection based on Exo III-catalyzed recycling coupled with rolling circle
      amplification.
AB  - A sensitive and label-free fluorescence assay for DNA detection has been
      developed based on cascade signal amplification combining exonuclease III (Exo
      III)-catalyzed recycling with rolling circle amplification. In this assay, probe
      DNA hybridized with template DNA was coupled onto magnetic nanoparticles to
      prepare a magnetic bead-probe (MNB-probe)-template complex. The complex could
      hybridize with the target DNA, which transformed the protruding 3' terminus of
      template DNA into a blunt end. Exo III could then digest template DNA, liberating
      the MNB-probe and target DNA. The intact target DNA then hybridized with other
      templates and released more MNB-probes. The liberated MNB-probe captured the
      primer, circular DNA and then initiated the rolling circle amplification (RCA)
      reaction, realizing a cascade signal amplification. Using this cascade
      amplification strategy, a sensitive DNA detection method was developed which was
      superior to many existing Exo III-based signal amplification methods. Moreover, N
      methyl mesoporphyrin IX, which had a pronounced structural selectivity for the G
      quadruplex, was used to combine with the G-quadruplex RCA products and generate a
      fluorescence signal, avoiding the need for any fluorophore-label probes. The
      spike and recovery experiments in a human serum sample indicated that our assay
      also had great potential for DNA detection in real biological samples. 

PMID- 24752172
TI  - Interstitial lung disease in children.
AB  - PURPOSE OF REVIEW: There has been tremendous progress in the approach to
      childhood interstitial lung diseases (chILD), with particular recognition that
      interstitial lung disease (ILD) in infants is often distinct from the forms that
      occur in older children and adults. Diagnosis is challenging because of the
      rarity of ILD and the fact that the presenting symptoms of ILD often overlap
      those of common respiratory disorders. This review summarizes the newly published
      recommendations for diagnosis and management, and highlights the recent
      scientific advances in several specific forms of chILD. RECENT FINDINGS: Clinical
      practice guidelines emphasize the role for chest computed tomography, genetic
      testing, and lung biopsy in the diagnostic evaluation of children with suspected
      ILD. Recent studies have better defined the characteristics and molecular
      understanding of several different forms of ILD, including neuroendocrine cell
      hyperplasia of infancy and ILD, due to mutations in genes affecting surfactant
      production and metabolism. Despite significant progress, definitive therapies are
      often lacking. SUMMARY: chILD encompasses a collection of rare, diffuse lung
      diseases. Timely recognition of children with suspected ILD and initiation of
      appropriate diagnostic evaluations will facilitate medical management. Systematic
      approaches to clinical care and further studies are needed to improve the
      outcomes of children with these rare disorders.

PMID- 24752173
TI  - Relationship of dendritic cell density, HMGB1 expression, and tumor-infiltrating
      lymphocytes in non-small cell lung carcinomas.
AB  - Lung cancer is the leading cause of cancer death worldwide and non-small cell
      lung carcinoma (NSCLC) is the most common type of lung carcinomas. In
      adenocarcinomas, the most frequent histologic type of NSCLC, dendritic cells
      (DCs) are localized in close contact with tumor cells, and tumor-infiltrating
      lymphocytes (TILs) are observed in the peritumoral zones. In NSCLC, no studies
      investigating the density of intratumoral DCs and their impact on the density of
      TILs have been performed. In addition, the role of the alarmin high-mobility
      group box1 (HMGB1) in intratumoral DCs recruitment has not been analyzed. In the
      present study, a total of 82 cases of advanced stages of NSCLC were included.
      Tissue samples were obtained from biopsies and autopsies. DCs in biopsies or
      combinations of DCs and NK cells, CD3 T lymphocytes, or CD8 T lymphocytes from
      autopsy specimens were quantified in high power fields. Also, distribution of
      HMGB1 in tumor cells was detected. In lung adenocarcinomas, irrespective of
      subclassification, high densities of infiltrating DCs directly associated to high
      densities of peritumoral TILs. A 2.5-fold increase in TILs was found in specimens
      with high densities of infiltrating DCs compared with TILs from adenocarcinomas
      with low densities of infiltrating DCs. High densities of infiltrating DCs were
      associated with lung adenocarcinomas expressing cytoplasmic or nuclear
      cytoplasmic HMGB1. Our results suggest that in adenocarcinoma patients, HMGB1
      produced by tumor cells recruits DCs, which associate to an increase of TILs.
      Encouraging tumor-DCs-T lymphocytes interactions should improve the quality of
      life and survival of NSCLC patients. 

PMID- 24752175
TI  - Type D personality in never depressed patients at their first acute coronary
      syndrome.

PMID- 24752171
TI  - Alternative splicing regulates vesicular trafficking genes in cardiomyocytes
      during postnatal heart development.
AB  - During postnatal development the heart undergoes a rapid and dramatic transition
      to adult function through transcriptional and post-transcriptional mechanisms,
      including alternative splicing (AS). Here we perform deep RNA-sequencing on RNA
      from cardiomyocytes and cardiac fibroblasts to conduct a high-resolution analysis
      of transcriptome changes during postnatal mouse heart development. We reveal
      extensive changes in gene expression and AS that occur primarily between
      postnatal days 1 and 28. Cardiomyocytes and cardiac fibroblasts show reciprocal
      regulation of gene expression reflecting differences in proliferative capacity,
      cell adhesion functions and mitochondrial metabolism. We further demonstrate that
      AS plays a role in vesicular trafficking and membrane organization. These AS
      transitions are enriched among targets of two RNA-binding proteins, Celf1 and
      Mbnl1, which undergo developmentally regulated changes in expression. Vesicular
      trafficking genes affected by AS during normal development (when Celf1 is
      downregulated) show a reversion to neonatal splicing patterns after Celf1 re
      expression in adults. Short-term Celf1 induction in adult animals results in
      disrupted transverse tubule organization and calcium handling. These results
      identify potential roles for AS in multiple aspects of postnatal heart
      maturation, including vesicular trafficking and intracellular membrane dynamics. 

PMID- 24752176
TI  - Epigenetic analyses and the distribution of repetitive DNA and resistance genes
      reveal the complexity of common bean (Phaseolus vulgaris L., Fabaceae)
      heterochromatin.
AB  - The common bean (Phaseolus vulgaris L.) is the main representative of its genus
      and one of most important sources of proteins in African and Latin American
      countries. Although it is a species with a small genome, its pericentromeric and
      subtelomeric heterochromatin fractions are interspersed with single-copy
      sequences and active genes, suggesting a less compartmentalized genome
      organization. The present study characterized its chromatin fractions,
      associating the distribution of repetitive sequences and resistance genes with
      histone and DNA epigenetic modifications with and without biotic stress.
      Immunostaining with H3K4me3 and H4K5ac were generally associated with euchromatic
      regions, whereas H3K9me2, H3K27me1, and 5mC preferentially labeled the
      pericentromeric heterochromatin. The 45S rDNA and centromeric DNA sequences were
      hypomethylated as were most of the terminal heterochromatic blocks. The largest
      of them, which is associated with resistance genes, was also hypomethylated after
      the plants were infected with virulent and avirulent strains of the fungus
      Colletotrichum lindemuthianum, suggesting no correlation with control of
      resistance gene expression. The results highlighted the differences between
      subtelomeric and pericentromeric heterochromatin as well as variation within the
      pericentromeric heterochromatin.

PMID- 24752177
TI  - Change in vitamin d levels occurs early after antiretroviral therapy initiation
      and depends on treatment regimen in resource-limited settings.
AB  - STUDY BACKGROUND: Vitamin D has wide-ranging effects on the immune system, and
      studies suggest that low serum vitamin D levels are associated with worse
      clinical outcomes in HIV. Recent studies have identified an interaction between
      antiretrovirals used to treat HIV and reduced serum vitamin D levels, but these
      studies have been done in North American and European populations. METHODS: Using
      a prospective cohort study design nested in a multinational clinical trial, we
      examined the effect of three combination antiretroviral (cART) regimens on serum
      vitamin D levels in 270 cART-naive, HIV-infected adults in nine diverse
      countries, (Brazil, Haiti, Peru, Thailand, India, Malawi, South Africa, Zimbabwe
      and the United States). We evaluated the change between baseline serum vitamin D
      levels and vitamin D levels 24 and 48 weeks after cART initiation. RESULTS: Serum
      vitamin D levels decreased significantly from baseline to 24 weeks among those
      randomized to efavirenz/lamivudine/zidovudine (mean change: -7.94 [95% Confidence
      Interval (CI) -10.42, -5.54] ng/ml) and efavirenz/emtricitabine/tenofovir-DF
      (mean change: -6.66 [95% CI -9.40, -3.92] ng/ml) when compared to those
      randomized to atazanavir/emtricitabine/didanosine-EC (mean change: -2.29 [95% CI 
      4.83, 0.25] ng/ml). Vitamin D levels did not change significantly between week 24
      and 48. Other factors that significantly affected serum vitamin D change included
      country (p<0.001), season (p<0.001) and baseline vitamin D level (p<0.001).
      CONCLUSION: Efavirenz-containing cART regimens adversely affected vitamin D
      levels in patients from economically, geographically and racially diverse
      resource-limited settings. This effect was most pronounced early after cART
      initiation. Research is needed to define the role of Vitamin D supplementation in
      HIV care.

PMID- 24752178
TI  - Correlates of complete childhood vaccination in East African countries.
AB  - BACKGROUND: Despite the benefits of childhood vaccinations, vaccination rates in
      low-income countries (LICs) vary widely. Increasing coverage of vaccines to 90%
      in the poorest countries over the next 10 years has been estimated to prevent 426
      million cases of illness and avert nearly 6.4 million childhood deaths worldwide.
      Consequently, we sought to provide a comprehensive examination of contemporary
      vaccination patterns in East Africa and to identify common and country-specific
      barriers to complete childhood vaccination. METHODS: Using data from the
      Demographic and Health Surveys (DHS) for Burundi, Ethiopia, Kenya, Rwanda,
      Tanzania, and Uganda, we looked at the prevalence of complete vaccination for
      polio, measles, Bacillus Calmette-Guerin (BCG) and DTwPHibHep (DTP) as
      recommended by the WHO among children ages 12 to 23 months. We conducted
      multivariable logistic regression within each country to estimate associations
      between complete vaccination status and health care access and sociodemographic
      variables using backwards stepwise regression. RESULTS: Vaccination varied
      significantly by country. In all countries, the majority of children received at
      least one dose of a WHO recommended vaccine; however, in Ethiopia, Tanzania, and
      Uganda less than 50% of children received a complete schedule of recommended
      vaccines. Being delivered in a public or private institution compared with being
      delivered at home was associated with increased odds of complete vaccination
      status. Sociodemographic covariates were not consistently associated with
      complete vaccination status across countries. CONCLUSIONS: Although no consistent
      set of predictors accounted for complete vaccination status, we observed
      differences based on region and the location of delivery. These differences point
      to the need to examine the historical, political, and economic context of each
      country in order to maximize vaccination coverage. Vaccination against these
      childhood diseases is a critical step towards reaching the Millennium Development
      Goal of reducing under-five mortality by two-thirds by 2015 and thus should be a
      global priority.

PMID- 24752180
TI  - Development of a Mapped Diabetes Community Program Guide for a Safety Net
      Population.
AB  - PURPOSE: Enhancing linkages between patients and community programs is
      increasingly recognized as a method for improving physical activity, nutrition,
      and weight management. Although interactive mapped community program guides may
      be beneficial, there remains a dearth of articles that describe the processes and
      practicalities of creating such guides. This article describes the development of
      an interactive web-based mapped community program guide at a safety net
      institution and the lessons learned from that process. CONCLUSIONS: This project
      demonstrated the feasibility of creating 2 maps: a program guide and a population
      health map. It also revealed some key challenges and lessons for future work in
      this area, particularly within safety net institutions. Our work underscores the
      need for developing partnerships outside the health care system and the
      importance of employing community-based participatory methods. In addition to
      facilitating improvements in individual wellness, mapping community programs has
      the potential to improve population health management by health care delivery
      systems such as hospitals, health centers, or public health systems, including
      city and state departments of health.

PMID- 24752179
TI  - Tissue-specific SMARCA4 binding at active and repressed regulatory elements
      during embryogenesis.
AB  - The SMARCA4 (also known as BRG1 in humans) chromatin remodeling factor is
      critical for establishing lineage-specific chromatin states during early
      mammalian development. However, the role of SMARCA4 in tissue-specific gene
      regulation during embryogenesis remains poorly defined. To investigate the genome
      wide binding landscape of SMARCA4 in differentiating tissues, we engineered a
      Smarca4(FLAG) knock-in mouse line. Using ChIP-seq, we identified ~51,000 SMARCA4
      associated regions across six embryonic mouse tissues (forebrain, hindbrain,
      neural tube, heart, limb, and face) at mid-gestation (E11.5). The majority of
      these regions was distal from promoters and showed dynamic occupancy, with most
      distal SMARCA4 sites (73%) confined to a single or limited subset of tissues. To
      further characterize these regions, we profiled active and repressive histone
      marks in the same tissues and examined the intersection of informative chromatin
      states and SMARCA4 binding. This revealed distinct classes of distal SMARCA4
      associated elements characterized by activating and repressive chromatin
      signatures that were associated with tissue-specific up- or down-regulation of
      gene expression and relevant active/repressed biological pathways. We further
      demonstrate the predicted active regulatory properties of SMARCA4-associated
      elements by retrospective analysis of tissue-specific enhancers and direct
      testing of SMARCA4-bound regions in transgenic mouse assays. Our results indicate
      a dual active/repressive function of SMARCA4 at distal regulatory sequences in
      vivo and support its role in tissue-specific gene regulation during embryonic
      development. 

PMID- 24752181
TI  - Crystal arthritis: Tendon damage in gout--a role for MSU crystals?

PMID- 24752183
TI  - Connective tissue diseases: S100A4 implicated in systemic sclerosis.

PMID- 24752184
TI  - Rheumatoid arthritis: Is imaging needed to define remission in rheumatoid
      arthritis?

PMID- 24752185
TI  - Osteoarthritis: OA guidelines: improving care or merely codifying practice?

PMID- 24752182
TI  - Fibrosis--a lethal component of systemic sclerosis.
AB  - Fibrosis is a pathological process characterized by excessive accumulation of
      connective tissue components in an organ or tissue. Fibrosis is produced by
      deregulated wound healing in response to chronic tissue injury or chronic
      inflammation, the hallmarks of rheumatic diseases. Progressive fibrosis, which
      distorts tissue architecture and results in progressive loss of organ function,
      is now recognized to be one of the major causes of morbidity and mortality in
      individuals with one of the most lethal rheumatic disease, systemic sclerosis
      (SSc). In this Review, we discuss the pathological role of fibrosis in SSc. We
      discuss the involvement of endothelium and pericyte activation, aberrant immune
      responses, endoplasmic reticulum stress and chronic tissue injury in the
      initiation of fibrosis in SSc. We then discuss fibroblast activation and
      myofibroblast differentiation that occurs in response to these initiating
      processes and is responsible for excessive accumulation of extracellular matrix.
      Finally, we discuss the chemical and mechanical signals that drive fibroblast
      activation and myofibroblast differentiation, which could serve as targets for
      new therapies for fibrosis in SSc. 

PMID- 24752187
TI  - A unique surface-initiated property of nanoparticles and application for the
      synthesis of hybrid organic-inorganic nanoparticles.
AB  - We report a unique property of nanoparticles to initiate acrylic acid and
      acrylamide solution polymerization under low air pressure conditions. This
      property could be applied to synthesize a wide variety of hybrid organic
      inorganic nanoparticles, which hold great promise for use in nanophotonics,
      catalysis, and medical applications. 

PMID- 24752186
TI  - Staphylococcus aureus Nuc2 is a functional, surface-attached extracellular
      nuclease.
AB  - Staphylococcus aureus is a prominent bacterial pathogen that causes a diverse
      range of acute and chronic infections. Recently, it has been demonstrated that
      the secreted nuclease (Nuc) enzyme is a virulence factor in multiple models of
      infection, and in vivo expression of nuc has facilitated the development of an
      infection imaging approach based on Nuc-activatable probes. Interestingly, S.
      aureus strains encode a second nuclease (Nuc2) that has received limited
      attention. With the growing interest in bacterial nucleases, we sought to
      characterize Nuc2 in more detail through localization, expression, and
      biochemical studies. Fluorescence microscopy and alkaline phosphatase
      localization approaches using Nuc2-GFP and Nuc2-PhoA fusions, respectively,
      demonstrated that Nuc2 is membrane bound with the C-terminus facing the
      extracellular environment, indicating it is a signal-anchored Type II membrane
      protein. Nuc2 enzyme activity was detectable on the S. aureus cell surface using
      a fluorescence resonance energy transfer (FRET) assay, and in time courses, both
      nuc2 transcription and enzyme activity peaked in early logarithmic growth and
      declined in stationary phase. Using a mouse model of S. aureus pyomyositis, Nuc2
      activity was detected with activatable probes in vivo in nuc mutant strains,
      demonstrating that Nuc2 is produced during infections. To assess Nuc2 biochemical
      properties, the protein was purified and found to cleave both single- and double
      stranded DNA, and it exhibited thermostability and calcium dependence,
      paralleling the properties of Nuc. Purified Nuc2 prevented biofilm formation in
      vitro and modestly decreased biomass in dispersal experiments. Altogether, our
      findings confirm that S. aureus encodes a second, surface-attached and functional
      DNase that is expressed during infections and displays similar biochemical
      properties to the secreted Nuc enzyme. 

PMID- 24752188
TI  - Inaccurate data in my meta-analysis of prolonged macrolides for patients with non
      cystic fibrosis bronchiectasis in adult.

PMID- 24752189
TI  - Ultra-high performance, high-temperature superconducting wires via cost
      effective, scalable, co-evaporation process.
AB  - Long-length, high-temperature superconducting (HTS) wires capable of carrying
      high critical current, Ic, are required for a wide range of applications. Here,
      we report extremely high performance HTS wires based on 5 MUm thick SmBa2Cu3O7-
      delta (SmBCO) single layer films on textured metallic templates. SmBCO layer
      wires over 20 meters long were deposited by a cost-effective, scalable co
      evaporation process using a batch-type drum in a dual chamber. All deposition
      parameters influencing the composition, phase, and texture of the films were
      optimized via a unique combinatorial method that is broadly applicable for co
      evaporation of other promising complex materials containing several cations.
      Thick SmBCO layers deposited under optimized conditions exhibit excellent cube-on
      cube epitaxy. Such excellent structural epitaxy over the entire thickness results
      in exceptionally high Ic performance, with average Ic over 1,000 A/cm-width for
      the entire 22 meter long wire and maximum Ic over 1,500 A/cm-width for a short 12
      cm long tape. The Ic values reported in this work are the highest values ever
      reported from any lengths of cuprate-based HTS wire or conductor.

PMID- 24752190
TI  - Hoarding without reward: rodent responses to repeated episodes of complete cache
      loss.
AB  - For food-hoarding strategies to be maintained in a population, the benefits of
      hoarding must outweigh the costs. If rewards are too low to offset the costs of
      hoarding, hoarders might be expected to abandon hoarding and/or shift to an
      alternative storing strategy (e.g., increase food consumption). However the
      ability to adjust to such circumstances requires that animals anticipate long
      term rewards and adjust storing strategies to modify future outcomes. To test
      this, we subjected three sympatric food-hoarding species (the Korean field mouse,
      Apodemus peninsulae, both a scatter and larder hoarder; the Chinese white-bellied
      rat, Niviventer confucianus, only a larder hoarder; and Pere David's rock
      squirrel, Sciurotamias davidianus, predominantly a scatter hoarder) to repeated
      episodes of complete cache loss over nine sequential trials in semi-natural
      enclosures. Although these species increased harvest and consumption rates
      throughout the experiment, none of these three species ceased hoarding under
      these conditions. The variation in responses observed across species and gender
      suggest some degree of behavioural plasticity to compensate for such extreme
      losses, but a general inability to abandon hoarding or shift to an alternative
      strategy. Future studies should consider how such responses correspond to natural
      patterns of intensive pilferage in the field. 

PMID- 24752191
TI  - Zinc halide template effects on the construction of [1 + 1] flexible Schiff-base
      macrocyclic complexes having pendant-armed dialdehyde components.
AB  - Two novel pendant-armed dialdehydes (1a and 1b) were prepared by a one-step
      reaction between 5-chloro-3-(chloromethyl)-2-hydroxybenzaldehyde/5-methyl-3
      (chloromethyl)-2-hydroxybenzaldehyde and cyclohexylamine involving two
      nucleophilic substitutions, and they were used to react with 1,3-propanediamine
      to prepare Schiff-base macrocyclic complexes in the presence of ZnX2 salts (X =
      Cl, Br, and I). As a result, five dinuclear (2a, 2b, 3b, 4a, and 4b) and one
      mononuclear (3a) [1 + 1] flexible macrocyclic Zn(II) complexes have been
      structurally and spectrally characterized. The zinc centers in three pairs of
      macrocyclic complexes have the common four-coordinate tetrahedral geometry with
      one or two coordinated halide ions, where the template Zn(II) cations and the
      auxiliary halide anions with different sizes and coordination abilities are
      believed to play important roles in forming the resulting macrocyclic complexes.
      In addition, subtle alterations of electron-withdrawing and electron-donating
      substituted groups (Cl versus CH3) in the macrocyclic backbone result in
      different (1)H NMR and UV-vis spectra.

PMID- 24752192
TI  - Effect of PIP3 on adhesion molecules and adhesion of THP-1 monocytes to HUVEC
      treated with high glucose.
AB  - BACKGROUND: Phosphatidylinositol-3,4,5-triphosphate (PIP3), a well-known lipid
      second messenger, plays a key role in insulin signaling and glucose homeostasis.
      Using human umbilical vein endothelial cells (HUVEC) and THP-1 monocytes, we
      tested the hypothesis that PIP3 can downregulate adhesion molecules and monocyte
      adhesion to endothelial cells. METHODS: HUVEC and monocytes were exposed to high
      glucose (HG, 25 mM, 20 h) with or without PIP3 (0-20 nM), or PIT-1 (25 uM), an
      inhibitor of PIP3. RESULTS: Both HG and PIT-1 caused a decrease in cellular PIP3
      in monocytes and HUVEC compared to controls. Treatment with PIT-1 and HG also
      increased the ICAM-1 (intercellular adhesion molecule 1) total protein expression
      as well as its surface expression in HUVEC, CD11a (a subunit of lymphocyte
      function-associated antigen 1, LFA-1) total protein expression as well as its
      surface expression in monocytes, and adhesion of monocytes to HUVEC. Exogenous
      PIP3 supplementation restored the intracellular PIP3 concentrations,
      downregulated the expression of adhesion molecules, and reduced the adhesion of
      monocytes to HUVEC treated with HG. CONCLUSION: This study reports that a
      decrease in cellular PIP3 is associated with increased expression of adhesion
      molecules and monocyte-endothelial cell adhesion, and may play a role in the
      endothelial dysfunction associated with diabetes.

PMID- 24752193
TI  - Validity and reliability of new agility test among elite and subelite under 14
      soccer players.
AB  - BACKGROUND: Agility is a determinant component in soccer performance. This study
      aimed to evaluate the reliability and sensitivity of a "Modified Illinois change
      of direction test" (MICODT) in ninety-five U-14 soccer players. METHODS: A total
      of 95 U-14 soccer players (mean +/- SD: age: 13.61 +/- 1.04 years; body mass:
      30.52 +/- 4.54 kg; height: 1.57 +/- 0.1 m) from a professional and semi
      professional soccer academy, participated to this study. Sixty of them took part
      in reliability analysis and thirty-two in sensitivity analysis. RESULTS: The
      intraclass correlation coefficient (ICC) that aims to assess relative reliability
      of the MICODT was of 0.99, and its standard error of measurement (SEM) for
      absolute reliability was <5% (1.24%). The MICODT's capacity to detect change is
      "good", it's SEM (0.10 s) was <= SWC (0.33 s). The MICODT is significantly
      correlated to the Illinois change of direction speed test (ICODT) (r = 0.77;
      p<0.0001). The ICODT's MDC95 (0.64 s) was twice about the MICODT's MDC95 (0.28
      s), indicating that MICODT presents better ability to detect true changes than
      ICODT. The MICODT provided good sensitivity since elite U-14 soccer players were
      better than non-elite one on MICODT (p = 0.005; dz = 1.01 [large]). This was
      supported by an area under the ROC curve of 0.77 (CI 95%, 0.59 to 0.89,
      p<0.0008). The difference observed in these two groups in ICODT was not
      statistically significant (p = 0.14; dz = 0.51 [small]), showing poor
      discriminant ability. CONCLUSION: MICODT can be considered as more suitable
      protocol for assessing agility performance level than ICODT in U-14 soccer
      players.

PMID- 24752194
TI  - Light propagation in conjugated polymer nanowires decoupled from a substrate.
AB  - Light-emitting conjugated polymer nanowires are vertically grown and remotely
      manipulated into a freestanding straight or curved structure in three-dimension.
      This approach enabled us to eliminate substrate coupling, a critical issue in
      nanowire photonics in the past decade. We for the first time accomplished
      characterization of propagation and bending losses of nanowires completely
      decoupled from a substrate. 

PMID- 24752195
TI  - Counterfeit Medical Devices: The Money You Save Up Front Will Cost You Big in the
      End.

PMID- 24752196
TI  - Assessment of Nasal Function After Tip Surgery With a Cephalic Hinged Flap of the
      Lateral Crura: A Randomized Clinical Trial.
AB  - BACKGROUND: Postrhinoplasty nasal obstruction has been ascribed to either
      postreductive narrowing of the midvault or dynamic collapse resulting from
      lateral wall insufficiency. Recently, clinicians have reported on various
      surgical techniques that maximally preserve alar cartilage integrity, unlike the
      earlier popular methods of tip reduction surgery. OBJECTIVES: The authors
      compared the effects of 2 rhinoplasty techniques: a cephalic trim (CT) of the
      lateral crura (LC) and a horizontal resection with cephalic hinged flap (HRCH) of
      the LC of the lower lateral cartilage (LLC). METHODS: Fifty-two patients who
      presented with a bulbous nasal tip deformity were randomly assigned to 1 of 2
      groups and underwent either CT of the LC or HRCH. Effects of the procedures were
      evaluated by both acoustic rhinometry (AR; first and second minimal cross
      sectional areas [MCA1 and MCA2, respectively]) and by subjective scoring on a
      global nasal obstruction visual analog scale (VAS). Assessments were made before
      and after rhinoplasty. RESULTS: MCA1 and MCA2 were increased after both CT and
      HRCH. This increase was significant on the right side for both CT (P < .001) and
      HRCH (P = .001), but the increase on the left side was significant only for HRCH.
      CONCLUSIONS: The improvement noted in breathing quality by VAS and AR suggests
      that a hinged flap may be effective in reconstructing the internal nasal valve.
      LEVEL OF EVIDENCE: 3.

PMID- 24752198
TI  - Matrix metalloproteinases and gut toxicity following cytotoxic cancer therapy.
AB  - PURPOSE OF REVIEW: Chemotherapy is an effective anticancer treatment; however, it
      induces mucositis in a wide range of patients. This condition is characterized by
      pain and ulceration, vomiting, bloating and diarrhea, depending on the area of
      the alimentary tract affected. Although treatment is available for a small subset
      of patients suffering from mucositis, the majority rely on pain relief as their
      only treatment option. Much progress has been made in recent years into
      understanding the pathobiology underlying the development of mucositis and matrix
      metalloproteinases (MMPs) have been implicated as being key mediators. The
      purpose of this review was to evaluate recent literature implicating MMPs in
      mucositis. RECENT FINDINGS: MMPs are well known for their roles in induction of
      inflammation and contribution to tissue injury. Recent literature provides a role
      for MMPs in mucositis development possibly through inflammatory pathways,
      alterations in extracellular matrix composition, adhesion molecules and tight
      junctions. SUMMARY: Better understanding of the precise roles of MMPs is now
      required in order to target appropriate treatment strategies.

PMID- 24752197
TI  - The role of the Niemann-Pick disease, type C1 protein in adipocyte insulin
      action.
AB  - The Niemann-Pick disease, type C1 (NPC1) gene encodes a transmembrane protein
      involved in cholesterol efflux from the lysosome. SNPs within NPC1 have been
      associated with obesity and type 2 diabetes, and mice heterozygous or null for
      NPC1 are insulin resistant. However, the molecular mechanism underpinning this
      association is currently undefined. This study aimed to investigate the effects
      of inhibiting NPC1 function on insulin action in adipocytes. Both pharmacological
      and genetic inhibition of NPC1 impaired insulin action. This impairment was
      evident at the level of insulin signalling and insulin-mediated glucose transport
      in the short term and decreased GLUT4 expression due to reduced liver X receptor
      (LXR) transcriptional activity in the long-term. These data show that cholesterol
      homeostasis through NPC1 plays a crucial role in maintaining insulin action at
      multiple levels in adipocytes. 

PMID- 24752201
TI  - Nanopapers for organic solvent nanofiltration.
AB  - Would it not be nice to have an organic solvent nanofiltration membrane made from
      renewable resources that can be manufactured as simply as producing paper? Here
      the production of nanofiltration membranes made from nanocellulose by applying a
      papermaking process is demonstrated. Manufacture of the nanopapers was enabled by
      inducing flocculation of nanofibrils upon addition of trivalent ions. 

PMID- 24752200
TI  - Two novel EHEC/EAEC hybrid strains isolated from human infections.
AB  - The so far highest number of life-threatening hemolytic uremic syndrome was
      associated with a food-borne outbreak in 2011 in Germany which was caused by an
      enterohemorrhagic Escherichia coli (EHEC) of the rare serotype O104:H4. Most
      importantly, the outbreak strain harbored genes characteristic of both EHEC and
      enteroaggregative E. coli (EAEC). Such strains have been described seldom but due
      to the combination of virulence genes show a high pathogenicity potential. To
      evaluate the importance of EHEC/EAEC hybrid strains in human disease, we analyzed
      the EHEC strain collection of the German National Reference Centre for Salmonella
      and other Bacterial Enteric Pathogens (NRC). After exclusion of O104:H4 EHEC/EAEC
      strains, out of about 2400 EHEC strains sent to NRC between 2008 and 2012, two
      strains exhibited both EHEC and EAEC marker genes, specifically were stx2 and
      aatA positive. Like the 2011 outbreak strain, one of the novel EHEC/EAEC harbored
      the Shiga toxin gene type stx2a. The strain was isolated from a patient with
      bloody diarrhea in 2010, was serotyped as O59:H-, belonged to MLST ST1136, and
      exhibited genes for type IV aggregative adherence fimbriae (AAF). The second
      strain was isolated from a patient with diarrhea in 2012, harbored stx2b, was
      typed as Orough:H-, and belonged to MLST ST26. Although the strain conferred the
      aggregative adherence phenotype, no known AAF genes corresponding to fimbrial
      types I to V were detected. In summary, EHEC/EAEC hybrid strains are currently
      rarely isolated from human disease cases in Germany and two novel EHEC/EAEC of
      rare serovars/MLST sequence types were characterized. 

PMID- 24752199
TI  - Descending pain modulation and chronification of pain.
AB  - PURPOSE OF REVIEW: Chronic pain is an important public health problem that
      negatively impacts quality of life of affected individuals and exacts an enormous
      socio-economic cost. Currently available therapeutics provide inadequate
      management of pain in many patients. Acute pain states generally resolve in most
      patients. However, for reasons that are poorly understood, in some individuals,
      acute pain can transform to a chronic state. Our understanding of the risk
      factors that underlie the development of chronic pain is limited. Recent studies
      have suggested an important contribution of dysfunction in descending pain
      modulatory circuits to pain 'chronification'. Human studies provide insights into
      possible endogenous and exogenous factors that may promote the conversion of pain
      into a chronic condition. RECENT FINDINGS: Descending pain modulatory systems
      have been studied and characterized in animal models. Human brain imaging
      techniques, deep brain stimulation and the mechanisms of action of drugs that are
      effective in the treatment of pain confirm the clinical relevance of top-down
      pain modulatory circuits. Growing evidence supports the concept that chronic pain
      is associated with a dysregulation in descending pain modulation. Disruption of
      the balance of descending modulatory circuits to favour facilitation may promote
      and maintain chronic pain. Recent findings suggest that diminished descending
      inhibition is likely to be an important element in determining whether pain may
      become chronic. This view is consistent with the clinical success of drugs that
      enhance spinal noradrenergic activity, such as serotonin/norepinephrine reuptake
      inhibitors (SNRIs), in the treatment of chronic pain states. Consistent with this
      concept, a robust descending inhibitory system may be normally engaged to protect
      against the development of chronic pain. Imaging studies show that higher
      cortical and subcortical centres that govern emotional, motivational and
      cognitive processes communicate directly with descending pain modulatory circuits
      providing a mechanistic basis to explain how exogenous factors can influence the
      expression of chronic pain in a susceptible individual. SUMMARY: Preclinical
      studies coupled with clinical pharmacologic and neuroimaging investigations have
      advanced our understanding of brain circuits that modulate pain. Descending pain
      facilitatory and inhibitory circuits arising ultimately in the brainstem provide
      mechanisms that can be engaged to promote or protect against pain
      'chronification'. These systems interact with higher centres, thus providing a
      means through which exogenous factors can influence the risk of pain
      chronification. A greater understanding of the role of descending pain modulation
      can lead to novel therapeutic directions aimed at normalizing aberrant processes
      that can lead to chronic pain.

PMID- 24752202
TI  - Palmar reconstruction of the triangular fibrocartilage complex for static
      instability of the distal radioulnar joint.
AB  - This study describes a new technique that can be used for reconstructing the
      triangular fibrocartilage complex to correct the static palmar radius instability
      of the distal radioulnar joint. In the abovementioned condition, the radius is
      extremely unstable with respect to the ulna and dislocates palmarly in the
      resting position. Using a palmar approach, a palmaris longus tendon graft was
      sutured to the remnant of the disrupted palmar radioulnar and ulnocarpal
      ligaments and then anchored to the bone tunnel that was created at the ulnar
      fovea. This technique predominantly reinforces the palmar structure of triangular
      fibrocartilage complex because the palmar radioulnar ligament is the most
      critical stabilizer of palmar radius instability. 

PMID- 24752204
TI  - The template effect of solvents on high yield synthesis, co-cyclization of
      pillar[6]arenes and interconversion between pillar[5]- and pillar[6]arenes.
AB  - We have synthesized a pillar[6]arene in high yield and a co-pillar[6]arene using
      chlorocyclohexane as a solvent. 

PMID- 24752203
TI  - Anti-inflammatory activity of N-butanol extract from Ipomoea stolonifera in vivo
      and in vitro.
AB  - Ipomoea stolonifera (I. stolonifera) has been used for the treatment of
      inflammatory diseases including rheumatism and rheumatoid arthritis in Chinese
      traditional medicine. However, the anti-inflammatory activity of I. stolonifera
      has not been elucidated. For this reason, the anti-inflammatory activity of n
      butanol extract of I. stolonifera (BE-IS) was evaluated in vivo by using acute
      models (croton oil-induced mouse ear edema, carrageenan-induced rat paw edema,
      and carrageenan-induced rat pleurisy) and chronic models (cotton pellet-induced
      rat granuloma, and complete Freund's adjuvant (CFA)-induced rat arthritis).
      Results indicated that oral administration of BE-IS significantly attenuated
      croton oil-induced ear edema, decreased carrageenan-induced paw edema, reduced
      carrageenan-induced exudates and cellular migration, inhibited cotton pellet
      induced granuloma formation and improved CFA-induced arthritis. Preliminary
      mechanism studies demonstrated that BE-IS decreased the levels of myeloperoxidase
      (MPO) and malondialdehyde (MDA), increased the activity of anti-oxidant enzyme
      superoxide dismutase (SOD) in vivo, and reduced the production of nitric oxide
      (NO), prostaglandin E2 (PGE2), tumor necrosis factor-alpha (TNF-alpha),
      interleukin (IL)-1beta and IL-6 in lipopolysaccharide-activated RAW264.7
      macrophages in vitro. Results obtained in vivo and in vitro demonstrate that BE
      IS has considerable anti-inflammatory potential, which provided experimental
      evidences for the traditional application of Ipomoea stolonifera in inflammatory
      diseases. 

PMID- 24752206
TI  - Capture-induced transition in foamy suspensions.
AB  - We investigate the drainage behaviour of foamy granular suspensions. Results
      reveal large fluctuations in the drainage velocity as bubble size, particle size
      and gas volume fraction are varied for a given particle volume fraction. Particle
      capture is proved to control the overall drainage behaviour through the parameter
      lambda, which compares the particle size to the size of passage through
      constrictions within the foam pore space. lambda highlights a sharp transition:
      for lambda < 1 particles are free to drain with the liquid, which involves the
      shear of the suspension in foam interstices, for lambda > 1 particles are trapped
      and the resulting drainage velocity is strongly reduced. A phenomenological model
      is proposed to describe this behaviour. 

PMID- 24752205
TI  - Phenolic acid composition, antiatherogenic and anticancer potential of honeys
      derived from various regions in Greece.
AB  - The phenolic acid profile of honey depends greatly on its botanical and
      geographical origin. In this study, we carried out a quantitative analysis of
      phenolic acids in the ethyl acetate extract of 12 honeys collected from various
      regions in Greece. Our findings indicate that protocatechuic acid, p
      hydroxybenzoic acid, vanillic acid, caffeic acid and p-coumaric acid are the
      major phenolic acids of the honeys examined. Conifer tree honey (from pine and
      fir) contained significantly higher concentrations of protocatechuic and caffeic
      acid (mean: 6640 and 397 ug/kg honey respectively) than thyme and citrus honey
      (mean of protocatechuic and caffeic acid: 437.6 and 116 ug/kg honey
      respectively). p-Hydroxybenzoic acid was the dominant compound in thyme honeys
      (mean: 1252.5 ug/kg honey). We further examined the antioxidant potential (ORAC
      assay) of the extracts, their ability to influence viability of prostate cancer
      (PC-3) and breast cancer (MCF-7) cells as well as their lowering effect on TNF-
      alpha-induced adhesion molecule expression in endothelial cells (HAEC). ORAC
      values of Greek honeys ranged from 415 to 2129 umol Trolox equivalent/kg honey
      and correlated significantly with their content in protocatechuic acid (p<0.001),
      p-hydroxybenzoic acid (p<0.01), vanillic acid (p<0.05), caffeic acid (p<0.01), p
      coumaric acid (p<0.001) and their total phenolic content (p<0.001). Honey
      extracts reduced significantly the viability of PC-3 and MCF-7 cells as well as
      the expression of adhesion molecules in HAEC. Importantly, vanillic acid content
      correlated significantly with anticancer activity in PC-3 and MCF-7 cells
      (p<0.01, p<0.05 respectively). Protocatechuic acid, vanillic acid and total
      phenolic content correlated significantly with the inhibition of VCAM-1
      expression (p<0.05, p<0.05 and p<0.01 respectively). In conclusion, Greek honeys
      are rich in phenolic acids, in particular protocatechuic and p-hydroxybenzoic
      acid and exhibit significant antioxidant, anticancer and antiatherogenic
      activities which may be attributed, at least in part, to their phenolic acid
      content. 

PMID- 24752207
TI  - Kidney cancer: progress and controversies in neoadjuvant therapy.
AB  - Use of clinically active agents, such as kinase inhibitors, before nephrectomy is
      safe and feasible and can decrease the size of primary tumours, enabling
      optimization of the surgical approach. However, the overall clinical benefit of
      the neoadjuvant use of toxic drugs, such as axitinib, has not yet been
      demonstrated.

PMID- 24752212
TI  - Rhythm patterns interaction--synchronization behavior for human-robot joint
      action.
AB  - Interactive behavior among humans is governed by the dynamics of movement
      synchronization in a variety of repetitive tasks. This requires the interaction
      partners to perform for example rhythmic limb swinging or even goal-directed arm
      movements. Inspired by that essential feature of human interaction, we present a
      novel concept and design methodology to synthesize goal-directed synchronization
      behavior for robotic agents in repetitive joint action tasks. The agents' tasks
      are described by closed movement trajectories and interpreted as limit cycles,
      for which instantaneous phase variables are derived based on oscillator theory.
      Events segmenting the trajectories into multiple primitives are introduced as
      anchoring points for enhanced synchronization modes. Utilizing both continuous
      phases and discrete events in a unifying view, we design a continuous dynamical
      process synchronizing the derived modes. Inverse to the derivation of phases, we
      also address the generation of goal-directed movements from the behavioral
      dynamics. The developed concept is implemented to an anthropomorphic robot. For
      evaluation of the concept an experiment is designed and conducted in which the
      robot performs a prototypical pick-and-place task jointly with human partners.
      The effectiveness of the designed behavior is successfully evidenced by objective
      measures of phase and event synchronization. Feedback gathered from the
      participants of our exploratory study suggests a subjectively pleasant sense of
      interaction created by the interactive behavior. The results highlight potential
      applications of the synchronization concept both in motor coordination among
      robotic agents and in enhanced social interaction between humanoid agents and
      humans. 

PMID- 24752213
TI  - Orthognathic surgery: pretreatment information and patient satisfaction.
AB  - OBJECTIVES: This study sought to (1) analyze the demographic profile of patients
      who completed combined orthodontic and surgical treatments at the Kuwait Ministry
      of Health dental clinics, (2) evaluate the source, type, amount and timing of
      preoperative patient information, (3) determine posttreatment patient
      satisfaction and (4) examine whether patient satisfaction is associated with
      preoperative information. SUBJECTS AND METHODS: Of the 145 patients who completed
      combined orthodontic and surgical treatments at least 6 months prior to the
      initiation of this study, 74 agreed to be interviewed by telephone by means of a
      structured survey including questions covering the study's objectives. RESULTS:
      The mean age of participants was 21.1 years; 52 (70.3%) were female and 22
      (29.7%) were male. Of these 74 patients, 70 (94%) did not regret their decision
      to undergo orthognathic surgery and 62 (83.8%) would repeat the same treatment if
      it was needed. The majority of the respondents reported that the importance of
      treatment compliance had been explained very well prior to surgery, but that
      information about the associated functional and social problems was lacking. The
      orthodontist was the most prominent source of information before treatment began.
      As the presurgical orthodontic treatment phase progressed, the roles of the
      surgeon and orthodontist became more evenly distributed. CONCLUSION: The patients
      who underwent orthognathic surgery were satisfied and generally well informed.
      However, information regarding surgical risks and functional discomforts was not
      adequate. Participants were more likely to be satisfied when they were provided
      with more information about discomfort and surgical risks.

PMID- 24752214
TI  - A colonization of basal cell carcinoma by malignant melanoma in situ resembling a
      malignant basomelanocytic tumor.
AB  - We report a case of colonization of basal cell carcinoma (BCC) by malignant
      melanoma in situ (MIS) simulating a malignant basomelanocytic tumor. A biopsy of
      a pigmented lesion present on an 83-year-old man's scalp displayed intimate
      admixing of basaloid and melanocytic cells. This seemingly inseparable
      combination of BCC and neoplastic melanocytes has been referred to as a malignant
      basomelanocytic tumor. However, our case also displays an adjacent component of
      MIS, thus favoring colonization of BCC by MIS as the etiology. To our knowledge,
      this is the third case report of colonization of BCC by MIS resembling a
      malignant basomelanocytic tumor.

PMID- 24752215
TI  - IgG/IgA pemphigus.
AB  - IgG/IgA pemphigus has recently been described in the literature as an overlap of
      pemphigus vulgaris or pemphigus foliaceus with IgA pemphigus. There has also been
      some postulation that this IgG/IgA pemphigus may be associated with internal
      malignancy as well. Our case demonstrates the unique clinical, histopathological,
      and direct immunofluorescence findings of IgG/IgA pemphigus and further
      highlights the possibility of association of this disease with internal
      malignancy.

PMID- 24752216
TI  - A primary systemic ALCL present initially as cutaneous localized skin lesions:
      report of an unusual case.
AB  - Anaplastic large cell lymphoma (ALCL) is classified into systemic and primary
      cutaneous subtypes. A primary systemic ALCL present initially as cutaneous
      localized skin lesions is a rare presentation. We present an unusual case of a 13
      year-old boy with systemic ALCL who presented with cutaneous nodules. The
      systemic nature of this lymphoma was confirmed by immunohistochemical positivity
      of anaplastic lymphoma kinase and epithelial membrane antigen. Confirmation of
      this diagnosis will lead to a poorer prognosis and more aggressive systemic
      therapy.

PMID- 24752217
TI  - Extramammary Paget disease of the vulva with underlying mammary-like lobular
      carcinoma: a case report and review of the literature.
AB  - Extramammary Paget disease of the vulva accounts for 1%-2% of the neoplasms of
      the anogenital area. Very rarely, extramammary Paget disease of the vulva has
      been associated with an underlying mammary-like carcinoma, usually ductal,
      extremely rarely mixed ductal and lobular. We report the case of a 60-year-old
      female with a recurrent extramammary Paget disease of the vulva. Pathological
      examination of the wide excision of the vulva revealed an extramammary Paget
      disease with an underlying invasive carcinoma composed of medium size cells
      organized in single files, a morphology similar to that of an invasive lobular
      breast carcinoma. Immunohistochemical staining showed a comparable profile in the
      Paget cells and in the invasive tumoral cells: CEA and CK7 positivity; GCDFP-15,
      ER focal positivity. E-cadherin and HER2 were diffusely positive. S100 and CK20
      were negative. HER2-CISH was amplified. The diagnosis of extramammary Paget
      disease of the vulva with an underlying mammary-like lobular carcinoma was made.
      Despite the characteristic lobular features, the immunohistochemical profile
      differs from the typical profile of a lobular carcinoma of the breast. The
      implications in term of prognostic and therapeutic significance need to be
      further studied.

PMID- 24752218
TI  - The molecular choreography of IRF4 and IRF8 with immune system partners.
AB  - The transcription factors IRF4 and IRF8 represent immune-specific members of the
      interferon regulatory family. They play major roles in controlling the
      development and functioning of innate and adaptive cells. Genes encoding these
      factors appear to have been coopted by the immune system via gene duplication and
      divergence of regulatory and protein coding sequences to enable the acquisition
      of unique molecular properties and functions. Unlike other members of the IRF
      family, IRF4 and IRF8 do not activate transcription of Type 1 interferon genes or
      positively regulate interferon-induced gene expression. Instead, they bind to
      unusual composite Ets-IRF or AP-1-IRF elements with specific Ets or AP-1 family
      transcription factors, respectively, and regulate the expression of diverse sets
      of immune response genes in innate as well as adaptive cells. 

PMID- 24752219
TI  - Role of calcium channels in the protective effect of hydrogen sulfide in rat
      cardiomyoblasts.
AB  - BACKGROUND: Hydrogen sulfide contributes to the reduction of oxidative stress
      related injury in cardiomyocytes but the underlying mechanism is still unclear.
      AIMS: Here we investigated the role of voltage-operated calcium channels (VOCCs)
      as mediators of the beneficial effect of H2S against oxidative stress in cultured
      rat cardiomyoblasts (H9c2). METHODS: Intracellular calcium signals were measured
      by fluorimetric live cell imaging and cell viability by colorimetric assay.
      RESULTS: Treatment with H2S donor (NaHS 10 uM) or Nifedipine (10 uM) decreased
      resting intracellular calcium concentration [Ca]i, suggesting that L-type VOCCs
      are negatively modulated by H2S. In the presence of Nifedipine H2S was still able
      to lower [Ca]i, while co-incubation with Nifedipine and Ni(2+) 100 uM completely
      prevented H2S-dependent [Ca]i decrease, suggesting that both L-type and T-type
      VOCCs are inhibited by H2S. In addition, in the same experimental conditions, H2S
      triggered a slow increase of [Ca]i whose molecular nature remains to be
      clarified. Pretreatment of H9c2 with NaHS (10 uM) significantly prevented cell
      death induced by H2O2. This effect was mimicked by pretreatment with L-Type
      calcium channel inhibitor Nifedipine (10 uM). CONCLUSIONS: The data provide the
      first evidence that H2S protects rat cardiomyoblasts against oxidative challenge
      through the inhibition of L-type calcium channels.

PMID- 24752220
TI  - NaYF4:Yb,Tm nanocrystals and TiO2 inverse opal composite films: a novel device
      for upconversion enhancement and solid-based sensing of avidin.
AB  - Upconversion luminescence (UCL) detection based on rare-earth doped upconversion
      nanocrystals (UCNCs) as probes has been proved to exhibit a large anti-Stokes
      shift, no autofluorescence from biological samples, and no photobleaching.
      However, it is still a challenge to achieve a stable, reproducible solid-based
      UCL biosensor because of ineffective UCL of the UCNCs. In this work, we
      fabricated TiO2 inverse opal photonic crystals (IOPCs)/NaYF4:Yb(3+),Tm(3+)
      (Er(3+)) UCNC composite films, which can tremendously improve the overall UCL of
      Tm(3+) as high as 43-fold. Based on the fluorescence resonance energy transfer
      (FRET) and the specific interaction between biotin and avidin, a novel solid
      based UC biosensor is presented for sensing avidin. This solid-based detection
      system is convenient for detection, and also can offer two parameters for
      detecting trace amounts of avidin, namely, the emission intensity and the
      fluorescence decay time. The sensor has a high sensitivity of 34 pmol(-1), a good
      linear relationship of 0.996 and a low detection limit of 48 pmol. It also
      exhibits excellent long-time photostability, and the absence of autofluorescence,
      and thus may have great potential for versatile applications in biodetection. 

PMID- 24752221
TI  - Utility of marine benthic associations as a multivariate proxy of
      paleobathymetry: a direct test from recent coastal ecosystems of North Carolina.
AB  - Benthic marine fossil associations have been used in paleontological studies as
      multivariate environmental proxies, with particular focus on their utility as
      water depth estimators. To test this approach directly, we evaluated modern
      marine invertebrate communities along an onshore-offshore gradient to determine
      the relationship between community composition and bathymetry, compare the
      performance of various ordination techniques, and assess whether restricting
      community datasets to preservable taxa (a proxy for paleontological data) and
      finer spatial scales diminishes the applicability of multivariate community data
      as an environmental proxy. Different indirect (unconstrained) ordination
      techniques (PCoA, CA, DCA, and NMDS) yielded consistent outcomes: locality Axis 1
      scores correlated with actual locality depths, and taxon Axis 1 scores correlated
      with actual preferred taxon depths, indicating that changes in faunal
      associations primarily reflect bathymetry, or its environmental correlatives. For
      datasets restricted to taxa with preservable hard parts, heavily biomineralized
      mollusks, open ocean habitats, and a single onshore-offshore gradient, the
      significant correlation between water depth and Axis 1 was still observed.
      However, for these restricted datasets, the correlation between Axis 1 and
      bathymetry was reduced and, in most cases, notably weaker than estimates produced
      by subsampling models. Consistent with multiple paleontological studies, the
      direct tests carried out here for a modern habitat using known bathymetry
      suggests that multivariate proxies derived from marine benthic associations may
      serve as a viable proxy of water depth. The general applicability of multivariate
      paleocommunity data as an indirect proxy of bathymetry is dependent on habitat
      type, intrinsic ecological characteristics of dominant faunas, taxonomic scope,
      and spatial and temporal scales of analysis, highlighting the need for continued
      testing in present-day depositional settings. 

PMID- 24752222
TI  - A pragmatic randomised controlled trial of dialectical behaviour therapy: effects
      on hospitalisation and post-treatment follow-up.

PMID- 24752223
TI  - Image registration algorithm using Mexican hat function-based operator and
      grouped feature matching strategy.
AB  - Feature detection and matching are crucial for robust and reliable image
      registration. Although many methods have been developed, they commonly focus on
      only one class of image features. The methods that combine two or more classes of
      features are still novel and significant. In this work, methods for feature
      detection and matching are proposed. A Mexican hat function-based operator is
      used for image feature detection, including the local area detection and the
      feature point detection. For the local area detection, we use the Mexican hat
      operator for image filtering, and then the zero-crossing points are extracted and
      merged into the area borders. For the feature point detection, the Mexican hat
      operator is performed in scale space to get the key points. After the feature
      detection, an image registration is achieved by using the two classes of image
      features. The feature points are grouped according to a standardized region that
      contains correspondence to the local area, precise registration is achieved
      eventually by the grouped points. An image transformation matrix is estimated by
      the feature points in a region and then the best one is chosen through
      competition of a set of the transformation matrices. This strategy has been named
      the Grouped Sample Consensus (GCS). The GCS has also ability for removing the
      outliers effectively. The experimental results show that the proposed algorithm
      has high registration accuracy and small computational volume. 

PMID- 24752224
TI  - Experimental demonstration of a graph state quantum error-correction code.
AB  - Scalable quantum computing and communication requires the protection of quantum
      information from the detrimental effects of decoherence and noise. Previous work
      tackling this problem has relied on the original circuit model for quantum
      computing. However, recently a family of entangled resources known as graph
      states has emerged as a versatile alternative for protecting quantum information.
      Depending on the graph's structure, errors can be detected and corrected in an
      efficient way using measurement-based techniques. Here we report an experimental
      demonstration of error correction using a graph state code. We use an all-optical
      setup to encode quantum information into photons representing a four-qubit graph
      state. We are able to reliably detect errors and correct against qubit loss. The
      graph we realize is setup independent, thus it could be employed in other
      physical settings. Our results show that graph state codes are a promising
      approach for achieving scalable quantum information processing. 

PMID- 24752226
TI  - The many faces of impaired bladder emptying.
AB  - PURPOSE OF REVIEW: Impaired bladder emptying is a common clinical problem for
      which currently no effective drug treatment is available. There has been an
      increasing interest in the condition, and the present review updates the
      terminology issues, common causes, and potential future pharmacological treatment
      possibilities. RECENT FINDINGS: Impaired bladder emptying can be described in
      many ways, but general agreement on the terminology has not yet been reached. The
      disorder can have many underlying causes, including aging, bladder outflow
      obstruction, diabetes mellitus, and neurogenic disturbances. There is no
      effective pharmacological treatment, and to what extent drug treatment of the
      associated morbidities (e.g., diabetes mellitus, Parkinson's disease, and
      multiple sclerosis) also can improve impaired bladder emptying has only been
      investigated to a limited extent. SUMMARY: Impaired bladder emptying may be
      caused by a spectrum of pathophysiologically defined disorders. To describe the
      condition, underactive bladder (UAB) can be used as a general term, covering
      detrusor underactivity as the urodynamic diagnosis, and the UAB syndrome for its
      symptomatic manifestations. In order to understand UAB, identification of the
      underlying cause(s) is necessary. Effective pharmacologic therapy is lacking and
      further basic research is needed to find targets for treatment.

PMID- 24752225
TI  - Non-mulberry silk fibroin influence osteogenesis and osteoblast-macrophage cross
      talk on titanium based surface.
AB  - The titanium and its alloys are used as orthopedic dental implants due to their
      mechanical and bio-inert properties. The bare metal implants are not the ultimate
      answer for better osteogenesis and implant integration. Physical and chemical
      modifications are carried out to achieve the goal of improved adhesion and
      differentiation of the osteoblast. In this work, the silk fibroins from both
      mulberry and non-mulberry sources are used for surface modification. Silk
      fibroins are immobilized on titanium surface to facilitate the initial cell
      adhesion followed by improved cell spreading and better mineralization in order
      to achieve enhanced osseointegration. The immunological responses along with the
      effect of cytokines on osteoblast adhesion and function are investigated. The non
      mulberry fibroin performs better in the context of the cell adherence and
      differentiation, which lead to better mineralization. The results indicate that
      the silk fibroin from non-mulberry source can be used for better osteogenesis on
      orthopedic implants. 

PMID- 24752227
TI  - LL-202, a newly synthesized flavonoid, inhibits tumor growth via inducing G(2)/M
      phase arrest and cell apoptosis in MCF-7 human breast cancer cells in vitro and
      in vivo.
AB  - We recently established that LL-202, a newly synthesized flavonoid, exhibited
      obvious anticancer effects against human breast cells in vivo and in vitro. The
      underlying mechanism of its anticancer activity remains to be elucidated. In this
      study, we demonstrated that LL-202 inhibited the growth and proliferation of
      human breast cancer MCF-7 cells in a concentration and time-dependent manner. We
      reported that LL-202 induced both mitochondrial- and death-receptor-mediated
      apoptosis, which were characterized by the dissipation of mitochondrial membrane
      potential (DeltaPsim), cytochrome c (Cyt c) release from mitochondria to cytosol,
      the activation of several caspases and induction of poly (ADP-ribose) polymerase
      (PARP) and Bid cleavage. N-acetylcysteine (NAC), a general ROS scavenger, partly
      blocked the LL-202-induced ROS levels and apoptosis. In addition, LL-202 induced
      arrest in cell cycle progression at G2/M phase in MCF-7 cells. After the
      treatment with LL-202, the expression of cell cycle-related proteins, such as
      cyclin B1, cyclin A, and p-CDK1 (Thr161) were down-regulated, whereas the
      expression of p21(WAF1/Cip1) and p-CDK1 (Thr14/Tyr15) were up-regulated. Finally,
      in vivo studies, LL-202 significantly suppressed the growth of MCF-7 breast
      cancer xenograft tumors in a dose-dependent manner with low systemic toxicity. In
      conclusion, the results showed that LL-202 had significant anticancer effects
      against human breast cells via the induction of apoptosis and G2/M phase arrest
      and it may be a novel anticancer agent for treatment of breast cancer. 

PMID- 24752228
TI  - Changes in corticospinal excitability during an acute bout of resistance exercise
      in the elbow flexors.
AB  - PURPOSE: Hypertrophic resistance exercise (HRE) induces central and peripheral
      fatigue. However, more detailed information about changes in corticospinal
      excitability remains to be elucidated. METHODS: Eleven volunteers participated in
      the upper arm HRE which included one repetition maximum (1 RM) control
      contractions and three sets of 13 RM (SET1-3). Transcranial magnetic stimulation
      (TMS) was applied during maximal isometric voluntary contraction (MVC) at the end
      of each set and during control contractions to study changes in corticospinal
      excitability. Electrical stimulation was used in order to measure peripheral
      changes. RESULTS: MVC decreased after each set when compared to control
      contractions. Motor evoked potential (MEP) were 138.7 +/- 52.7 % (p < 0.05),
      130.4 +/- 44.7 and 113.1 +/- 31.4 % after SET1, SET2 and SET3, respectively, when
      compared to pre-exercise value. A significant reduction in MEP area between SET1
      and SET3 (p < 0.05) was observed while silent period (SP) duration increased
      (~151-165 ms, p < 0.05) simultaneously between these sets. TMS-evoked twitch
      force during MVC increased significantly following each set when compared to pre
      exercise value. Simultaneously, a significant reduction was observed in resting
      twitch force over the sets. CONCLUSIONS: The results of this study clearly
      support the existence of both central and peripheral fatigue during HRE of elbow
      flexors. However, changes in the MEP area and SP suggest that during HRE of the
      elbow flexors, the corticospinal excitability increases first, until at some
      point, supraspinal fatigue takes over.

PMID- 24752230
TI  - Winter refuge for Aedes aegypti and Ae. albopictus mosquitoes in Hanoi during
      Winter.
AB  - Dengue occurs throughout the year in Hanoi, Vietnam, despite winter low
      temperatures <10 degrees C. During July 2010 to March 2012, we surveyed monthly
      for Aedes larvae and pupae in 120 houses in 8 Hanoi districts. Aedes albopictus
      preferred discarded containers in summer and pupal density drastically decreased
      in winter. Aedes aegypti preferred concrete tanks and this preference increased
      in winter. Even in winter, the lowest water temperature found in concrete tanks
      was >14 degrees C, exceeding the developmental zero point of Ae. aegypti.
      Although jars, drums and concrete tanks were the dominant containers previously
      (1994-97) in Hanoi, currently the percentage of residences with concrete tanks
      was still high while jars and drums were quite low. Our study showed that
      concrete tanks with broken lids allowing mosquitoes access were important winter
      refuge for Ae. aegypti. We also indicate a concern about concrete tanks serving
      as foci for Ae. aegypti to expand their distribution in cooler regions. 

PMID- 24752231
TI  - Deformation and dynamics of red blood cells in flow through cylindrical
      microchannels.
AB  - The motion of red blood cells (RBCs) in microcirculation plays an important role
      in blood flow resistance and in the cell partitioning within a microvascular
      network. Different shapes and dynamics of RBCs in microvessels have been
      previously observed experimentally including the parachute and slipper shapes. We
      employ mesoscale hydrodynamic simulations to predict the phase diagram of shapes
      and dynamics of RBCs in cylindrical microchannels, which serve as idealized
      microvessels, for a wide range of channel confinements and flow rates. A rich
      dynamical behavior is found, with snaking and tumbling discocytes, slippers
      performing a swinging motion, and stationary parachutes. We discuss the effects
      of different RBC states on the flow resistance, and the influence of RBC
      properties, characterized by the Foppl-von Karman number, on the shape diagram.
      The simulations are performed using the same viscosity for both external and
      internal fluids surrounding a RBC; however, we discuss how the viscosity contrast
      would affect the shape diagram. 

PMID- 24752229
TI  - In vivo image analysis of BoHV-4-based vector in mice.
AB  - Due to its biological characteristics bovine herpesvirus 4 (BoHV-4) has been
      considered as an appropriate gene delivery vector. Its genomic clone, modified as
      a bacterial artificial chromosome (BAC), is better genetically manipulable and
      can be used as an efficient gene delivery and vaccine vector. Although a large
      amount of data have been accumulated in vitro on this specific aspect, the same
      cannot be asserted for the in vivo condition. Therefore, here we investigated the
      fate of a recombinant BoHV-4 strain expressing luciferase (BoHV-4-A
      CMVlucDeltaTK) after intraperitoneal or intravenous inoculation in mice, by
      generating a novel recombinant BoHV-4 expressing luciferase (BoHV-4-A
      CMVlucDeltaTK) and by following the virus replication through in vivo imaging
      analysis. BoHV-4-A-CMVlucDeltaTK was first characterized in vitro where it was
      shown, on one hand that its replication properties are identical to those of the
      parental virus, and on the other that the transduced/infected cells strongly
      express luciferase. When BoHV-4-A-CMVlucDeltaTK was inoculated in mice, either
      intraperitoneally or intravenously, BoHV-4-A-CMVlucDeltaTK infection/transduction
      was exclusively localized to the liver, as detected by in vivo image analysis,
      and in particular almost exclusively in the hepatocytes, as determined by immuno
      histochemistry. These data, that add a new insight on the biology of BoHV-4 in
      vivo, provide the first indication for the potential use of a BoHV-4-based vector
      in gene-transfer in the liver. 

PMID- 24752232
TI  - Prediction of flexibility of metal-organic frameworks CAU-13 and NOTT-300 by
      first principles molecular simulations.
AB  - Based on first principles calculations, we predict and characterize the
      flexibility of two aluminium-based Metal-Organic Frameworks (MOFs), CAU-13 and
      NOTT-300. Both materials have a wine rack topology similar to that of MIL-53(Al),
      the archetypal breathing MOF, yet their flexibility has not been demonstrated so
      far. 

PMID- 24752233
TI  - Assessing Challenges in End-of-Life Conversations With Patients Utilizing a
      Public Safety-Net Health Care System.
AB  - Multiple factors influence end-of-life (EOL) care discussions that occur in
      health care systems, within organizations, among individuals working within these
      systems and in patients and family/friend support networks. This study examined
      barriers to EOL care discussions as experienced by health care providers working
      in a public safety-net health care system where the majority of their patients
      were low-income and immigrant Latinos seeking medical treatment. Qualitative data
      were collected in South Central Los Angeles through semistructured interviews
      with 46 health care providers from different disciplines in medicine, nursing,
      social work, and chaplaincy. The themes indicated communication barriers in the
      public sector health care setting and sociocultural patient- and family-level
      factors. All providers made valuable contributions to clarify the complexity of
      the problems. Universal strategies are needed to improve communication. 

PMID- 24752234
TI  - Chitinase expression in Listeria monocytogenes is positively regulated by the Agr
      system.
AB  - The food-borne pathogen Listeria monocytogenes encodes two chitinases, ChiA and
      ChiB, which allow the bacterium to hydrolyze chitin, the second most abundant
      polysaccharide in nature. Intriguingly, despite the absence of chitin in human
      and mammalian hosts, both of the chitinases have been deemed important for
      infection, through a mechanism that, at least in the case of ChiA, involves
      modulation of host immune responses. In this study, we show that the expression
      of the two chitinases is subject to regulation by the listerial agr system, a
      homologue of the agr quorum-sensing system of Staphylococcus aureus, that has so
      far been implicated in virulence and biofilm formation. We demonstrate that in
      addition to these roles, the listerial agr system is required for efficient
      chitin hydrolysis, as deletion of agrD, encoding the putative precursor of the
      agr autoinducer, dramatically decreased chitinolytic activity on agar plates. Agr
      was specifically induced in response to chitin addition in stationary phase and
      agrD was found to regulate the amount of chiA, but not chiB, transcripts.
      Although the transcript levels of chiB did not depend on agrD, the extracellular
      protein levels of both chitinases were reduced in the DeltaagrD mutant. The
      regulatory effect of agr on chiA is potentially mediated through the small RNA
      LhrA, which we show here to be negatively regulated by agr. LhrA is in turn known
      to repress chiA translation by binding to the chiA transcript and interfering
      with ribosome recruitment. Our results highlight a previously unrecognized role
      of the agr system and suggest that autoinducer-based regulation of chitinolytic
      systems may be more commonplace than previously thought. 

PMID- 24752236
TI  - Drosophila myeloid leukemia factor acts with DREF to activate the JNK signaling
      pathway.
AB  - Drosophila myelodysplasia/myeloid leukemia factor (dMLF), a homolog of human
      MLF1, oncogene was first identified by yeast two-hybrid screen using the DNA
      replication-related element-binding factor (DREF) as bait. DREF is a
      transcription factor that regulates proliferation-related genes in Drosophila. It
      is known that overexpression of dMLF in the wing imaginal discs through the
      engrailed-GAL4 driver causes an atrophied wing phenotype associated with the
      induction of apoptosis. However, the precise mechanisms involved have yet to be
      clarified. Here, we found the atrophied phenotype to be suppressed by loss-of
      function mutation of Drosophila Jun N-terminal kinase (JNK), basket (bsk).
      Overexpression of dMLF induced ectopic JNK activation in the wing disc monitored
      with the puckered-lacZ reporter line, resulting in induction of apoptosis. The
      DREF-binding consensus DRE sequence could be shown to exist in the bsk promoter.
      Chromatin immunoprecipitation assays in S2 cells with anti-dMLF IgG and
      quantitative real-time PCR revealed that dMLF binds specifically to the bsk
      promoter region containing the DRE sequence. Furthermore, using a transient
      luciferase expression assay, we provide evidence that knockdown of dMLF reduced
      bsk gene promoter activity in S2 cells. Finally, we show that dMLF interacts with
      DREF in vivo. Altogether, these data indicate that dMLF acts with DREF to
      stimulate the bsk promoter and consequently activates the JNK pathway to promote
      apoptosis. 

PMID- 24752235
TI  - Meta-analysis of the global gene expression profile of triple-negative breast
      cancer identifies genes for the prognostication and treatment of aggressive
      breast cancer.
AB  - Triple-negative breast cancer (TNBC) is an aggressive breast cancer subtype
      lacking expression of estrogen and progesterone receptors (ER/PR) and HER2, thus
      limiting therapy options. We hypothesized that meta-analysis of TNBC gene
      expression profiles would illuminate mechanisms underlying the aggressive nature
      of this disease and identify therapeutic targets. Meta-analysis in the Oncomine
      database identified 206 genes that were recurrently deregulated in TNBC compared
      with non-TNBC and in tumors that metastasized or led to death within 5 years.
      This 'aggressiveness gene list' was enriched for two core functions/metagenes:
      chromosomal instability (CIN) and ER signaling metagenes. We calculated an
      'aggressiveness score' as the ratio of the CIN metagene to the ER metagene, which
      identified aggressive tumors in breast cancer data sets regardless of subtype or
      other clinico-pathological indicators. A score calculated from six genes from the
      CIN metagene and two genes from the ER metagene recapitulated the aggressiveness
      score. By multivariate survival analysis, we show that our aggressiveness scores
      (from 206 genes or the 8 representative genes) outperformed several published
      prognostic signatures. Small interfering RNA screen revealed that the CIN
      metagene holds therapeutic targets against TNBC. Particularly, the inhibition of
      TTK significantly reduced the survival of TNBC cells and synergized with
      docetaxel in vitro. Importantly, mitosis-independent expression of TTK protein
      was associated with aggressive subgroups, poor survival and further stratified
      outcome within grade 3, lymph node-positive, HER2-positive and TNBC patients. In
      conclusion, we identified the core components of CIN and ER metagenes that
      identify aggressive breast tumors and have therapeutic potential in TNBC and
      aggressive breast tumors. Prognostication from these metagenes at the mRNA level
      was limited to ER-positive tumors. However, we provide evidence that mitosis
      independent expression of TTK protein was prognostic in TNBC and other aggressive
      breast cancer subgroups, suggesting that protection of CIN/aneuploidy drives
      aggressiveness and treatment resistance. 

PMID- 24752237
TI  - MicroRNA-18a is elevated in prostate cancer and promotes tumorigenesis through
      suppressing STK4 in vitro and in vivo.
AB  - MicroRNAs (miRNAs) comprise a class of short, non-coding RNAs that regulate
      protein synthesis through posttranscriptional modifications. In this study, we
      found significant upregulation of miR-18a in prostate cancer specimens and
      prostate cancer cell lines compared with the normal controls. MiRNAs can be
      separated into two groups based on whether they regulate tumor suppressors or
      oncogenes. In our previous study, we found that miR-18a, which belongs to the
      miR17-92 cluster, is upregulated in prostate cancer; the objective of this study
      was to investigate the associated regulatory mechanisms. We found that miR-18a is
      upregulated in clinical tumor specimens and cancer cell lines. Our bioinformatics
      analysis showed that the serine/threonine-protein kinase 4 (STK4) 3' untranslated
      region contains a highly conserved binding site for the miR-18a seed region.
      Luciferase reporter assays were performed to indicate that STK4 is a direct
      target of miR-18a. Interestingly, miR-18a knockdown decreased cell growth in
      prostate cancer cells and significantly decreased prostate tumor growth in in
      vivo nude mice experiments through STK4-mediated dephosphorylation of AKT and
      thereby inducing apoptosis. Our results suggest that miR-18a acts as an oncomiR
      targeting STK4 in prostate cancer, and inhibition of miR-18a expression may offer
      therapeutically beneficial option for prostate cancer treatment. 

PMID- 24752238
TI  - Genome-wide linkage analysis and association study identifies loci for
      polydactyly in chickens.
AB  - Polydactyly occurs in some chicken breeds, but the molecular mechanism remains
      incompletely understood. Combined genome-wide linkage analysis and association
      study (GWAS) for chicken polydactyly helps identify loci or candidate genes for
      the trait and potentially provides further mechanistic understanding of this
      phenotype in chickens and perhaps other species. The linkage analysis and GWAS
      for polydactyly was conducted using an F2 population derived from Beijing-You
      chickens and commercial broilers. The results identified two QTLs through linkage
      analysis and seven single-nucleotide polymorphisms (SNPs) through GWAS,
      associated with the polydactyly trait. One QTL located at 35 cM on the GGA2 was
      significant at the 1% genome-wise level and another QTL at the 1% chromosome-wide
      significance level was detected at 39 cM on GGA19. A total of seven SNPs, four of
      5% genome-wide significance (P < 2.98 * 10(-6)) and three of suggestive
      significance (5.96 * 10(-5)) were identified, including two SNPs (GGaluGA132178
      and Gga_rs14135036) in the QTL on GGA2. Of the identified SNPs, the eight nearest
      genes were sonic hedgehog (SHH), limb region 1 homolog (mouse) (LMBR1),
      dipeptidyl-peptidase 6, transcript variant 3 (DPP6), thyroid-stimulating hormone,
      beta (TSHB), sal-like 4 (Drosophila) (SALL4), par-6 partitioning defective 6
      homolog beta (Caenorhabditis elegans) (PARD6B), coenzyme Q5 (COQ5), and tyrosine
      3-monooxygenase/tryptophan 5-monooxygenase activation protein, etapolypeptide
      (YWHAH). The GWAS supports earlier reports of the importance of SHH and LMBR1 as
      regulating genes for polydactyly in chickens and other species, and identified
      others, most of which have not previously been associated with limb development.
      The genes and associated SNPs revealed here provide detailed information for
      further exploring the molecular and developmental mechanisms underlying
      polydactyly.

PMID- 24752239
TI  - New GO-PEI-Au-L-Cys ZIC-HILIC composites: synthesis and selective enrichment of
      glycopeptides.
AB  - GO-PEI-Au-L-Cys composites were synthesized via loading gold nanoparticles on a
      GO surface using polyethylenimine as reducing and stabilizing reagents, followed
      by L-cysteine immobilization through an Au-S bond. The composites were applied as
      a kind of novel ZIC-HILIC material to achieve highly selective enrichment of
      glycopeptides from biological samples.

PMID- 24752241
TI  - Fluctuations in intraocular pressure increase the trabecular meshwork
      extracellular matrix.
AB  - BACKGROUND/AIMS: The trabecular meshwork (TM) tissue is constantly exposed to
      dynamic stress caused by intraocular pressure (IOP). The effects of such
      biomechanical stress on the TM have not been analyzed. This study developed an
      animal model of fluctuating IOP and evaluated the effects of these fluctuations
      on TM tissue. METHODS: To create fluctuation in the IOP, one eye of adult SD rats
      was exposed to cyclic stress with IOP fluctuation ranging from 5 mmHg to 45 mmHg
      at a 1/60 Hz frequency for 30 minutes every day for several weeks. The other eye
      was not treated and served as the control. Hematoxylin-eosin staining was used to
      evaluate changes in the ganglion cells and the morphology, thickness and density
      of the TM; immunohistochemistry was used to detect alpha-smooth muscle actin
      (alpha-SMA), laminin (LA) and fibronectin (FN) expression in the TM. RESULTS:
      After several weeks of daily IOP fluctuation, the TM thickness remained
      unchanged, whereas the density dramatically increased. alpha-SMA, LA and FN were
      expressed in rat TM tissue, and the percentages of areas with positive expression
      significantly increased. The IOP was similar in the treated and control eyes and
      only tended to increase on day 22 of the experiment. Throughout the 28-day
      experiment, no ganglion cells were lost. CONCLUSIONS: Large fluctuations in IOP
      promoted the synthesis of alpha-SMA, LA and FN in the TM and increased the
      density of the TM, suggesting that fluctuations in IOP can induce pathological
      changes in the TM.

PMID- 24752240
TI  - Cell adhesion in zebrafish embryos is modulated by March 8.
AB  - March 8 is a member of a family of transmembrane E3 ubiquitin ligases that have
      been studied mostly for their role in the immune system. We find that March 8 is
      expressed in the zebrafish egg and early embryo, suggesting a role in
      development. Both knock-down and overexpression of March 8 leads to abnormal
      development. The phenotype of zebrafish embryos and Xenopus animal explants
      overexpressing March 8 implicates impairment of cell adhesion as a cause of the
      effect. In zebrafish embryos and in cultured cells, overexpression of March 8
      leads to a reduction in the surface levels of E-cadherin, a major cell-cell
      adhesion molecule. Experiments in cell culture further show that E-cadherin can
      be ubiquitinated by March 8. On the basis of these observations we suggest that
      March 8 functions in the embryo to modulate the strength of cell adhesion by
      regulating the localization of E-cadherin.

PMID- 24752243
TI  - Detection of Abeta plaques in mouse brain by using a disaggregation-induced
      fluorescence-enhancing probe.
AB  - We herein report a fluorescence probe 1 capable of detecting water-soluble
      oligomeric Abeta aggregates and Abeta fibrils. Upon injection into Abeta42
      challenged mouse brains, probe 1 shows increased fluorescence intensity,
      indicating its facile binding to extracellular Abeta fibrils in brain tissues. 

PMID- 24752242
TI  - Non-muscle myosin II regulates neuronal actin dynamics by interacting with
      guanine nucleotide exchange factors.
AB  - BACKGROUND: Non-muscle myosin II (NM II) regulates a wide range of cellular
      functions, including neuronal differentiation, which requires precise spatio
      temporal activation of Rho GTPases. The molecular mechanism underlying the NM II
      mediated activation of Rho GTPases is poorly understood. The present study
      explored the possibility that NM II regulates neuronal differentiation,
      particularly morphological changes in growth cones and the distal axon, through
      guanine nucleotide exchange factors (GEFs) of the Dbl family. PRINCIPAL FINDINGS:
      NM II colocalized with GEFs, such as betaPIX, kalirin and intersectin, in growth
      cones. Inactivation of NM II by blebbistatin (BBS) led to the increased formation
      of short and thick filopodial actin structures at the periphery of growth cones.
      In line with these observations, FRET analysis revealed enhanced Cdc42 activity
      in BBS-treated growth cones. BBS treatment also induced aberrant targeting of
      various GEFs to the distal axon where GEFs were seldom observed under
      physiological conditions. As a result, numerous protrusions and branches were
      generated on the shaft of the distal axon. The disruption of the NM II-GEF
      interactions by overexpression of the DH domains of betaPIX or Tiam1, or by
      betaPIX depletion with specific siRNAs inhibited growth cone formation and
      induced slender axons concomitant with multiple branches in cultured hippocampal
      neurons. Finally, stimulation with nerve growth factor induced transient
      dissociation of the NM II-GEF complex, which was closely correlated with the
      kinetics of Cdc42 and Rac1 activation. CONCLUSION: Our results suggest that NM II
      maintains proper morphology of neuronal growth cones and the distal axon by
      regulating actin dynamics through the GEF-Rho GTPase signaling pathway.

PMID- 24752244
TI  - Lord's paradox in a continuous setting and a regression artifact in numerical
      cognition research.
AB  - In this paper we review, and elaborate on, the literature on a regression
      artifact related to Lord's paradox in a continuous setting. Specifically, the
      question is whether a continuous property of individuals predicts improvement
      from training between a pretest and a posttest. If the pretest score is included
      as a covariate, regression to the mean will lead to biased results if two
      critical conditions are satisfied: (1) the property is correlated with pretest
      scores and (2) pretest scores include random errors. We discuss how these
      conditions apply to the analysis in a published experimental study, the authors
      of which concluded that linearity of children's estimations of numerical
      magnitudes predicts arithmetic learning from a training program. However, the two
      critical conditions were clearly met in that study. In a reanalysis we find that
      the bias in the method can fully account for the effect found in the original
      study. In other words, data are consistent with the null hypothesis that
      numerical magnitude estimations are unrelated to arithmetic learning. 

PMID- 24752245
TI  - Prevascular hernias of the abdominal wall: a difficult problem, a difficult
      repair.
AB  - INTRODUCTION: Secondary prevascular hernias occurring anterior to the iliofemoral
      vessels and involving the lower abdominal wall are rare. These hernias can be
      difficult to repair because of loss of the inguinal ligament and the
      musculofascial elements of the inguinal region. MATERIALS AND METHODS: We
      describe a new technique of repair using an intraperitoneal sling of prosthetic
      material. The sling is sewn posteriorly to the anterior surface of the sacrum,
      and is then draped caudally to be sewn to the pubis and Cooper's ligaments before
      being reflected anterior to be sewn to the posterior surface of the anterior
      abdominal wall. This sling "patches" the hernia defect as a form of
      intraperitoneal sublay. CONCLUSIONS: We describe three such patients with
      satisfactory results at follow-ups of 8-16 months. Potential problems and
      considerations are discussed.

PMID- 24752247
TI  - Incentive structure in team-based learning: graded versus ungraded Group
      Application exercises.
AB  - PURPOSE: Previous studies on team-based learning (TBL) in medical education
      demonstrated improved learner engagement, learner satisfaction, and academic
      performance; however, a paucity of information exists on modifications of the
      incentive structure of "traditional" TBL practices. The current study
      investigates the impact of modification to conventional Group Application
      exercises by examining student preference and student perceptions of TBL outcomes
      when Group Application exercises are excluded from TBL grades. METHODS: During
      the 2009-2010 and 2010-2011 academic years, 175 students (95.6% response rate)
      completed a 22-item multiple choice survey followed by 3 open response questions
      at the end of their second year of medical school. These students had
      participated in a TBL supplemented preclinical curriculum with graded Group
      Application exercises during year one and ungraded Group Application exercises
      during year two of medical school. RESULTS: Chi-square analyses showed
      significant differences between grading categories for general assessment of TBL,
      participation and communication, intra-team discussion, inter-team discussion,
      student perceptions of their own effort and development of teamwork skills.
      Furthermore, 83.8% of students polled prefer ungraded Group Application exercises
      with only 7.2% preferring graded and 9.0% indicating no preference. CONCLUSION:
      The use of ungraded Group Application exercises appears to be a successful
      modification of TBL, making it more "student-friendly" while maintaining the
      goals of active learning and development of teamwork skills.

PMID- 24752246
TI  - Wide nervous section to prevent post-operative inguinodynia after prosthetic
      hernia repair: a single center experience.
AB  - BACKGROUND: Chronic post-operative inguinodynia occurs in about 10 % of patients
      undergoing inguinal hernioplasty with prosthesis; it is characterized by a broad
      pleomorphism of symptoms, including relative to individual variability of algic
      perception. Its intensity can also potentially jeopardize patient's work and
      social activities. The most notorious cause of inguinodynia is neuropathy,
      resulting from the involvement of one or more inguinal nerves (iliohypogastric,
      ilioinguinal and genitofemoral nerves) in fibroblastic processes, or from nervous
      stimulation, caused by prosthetic material on adjacent nervous trunks. The aim of
      our study was to provide a comparative analysis between outcomes of wide nerve
      resection vs. nerve sparing. PATIENTS AND METHODS: In our hospital, between 2000
      and 2010, 600 patients underwent monolateral prosthetic inguinal hernia repair,
      using the original Trabucco technique. In 345 cases, to avoid chronic post
      operative pain, we carried out intentional neurectomy, between 3 and 8 cm in
      length of either the main and/or peripheral branches of the iliohypogastric
      nerve, ilioinguinal nerve and the genital branch of the genitofemoral nerve,
      deemed at risk of entrapment because of the prosthetic material. In the control
      group, which included the other 255 patients, nerves were identified and spared.
      Follow-up was scheduled at 1 week, 1 month and 1 year after surgery. RESULTS: 
      CASE: 1 week after the operation, 135 patients (39.1 %) did not show pain, 201
      (58.3 %) reported moderate pain and 9 (2.6 %) showed intense pain; 1 month after
      the procedure, 300 patients (87 %) did not have pain, 39 (11.3 %) complained of
      moderate pain and 6 (1.7 %) demonstrated severe pain; 1 year after surgery, only
      two patients (0.6 %) complained of persistent pain. CONTROL: At the 1-week follow
      up, 114 patients (44.7 %) did not show pain, 111 (43.5 %) reported moderate pain
      and 30 (11.8 %) intense pain; 1 month after the procedure, 183 patients (71.8 %)
      did not have pain, 45 (17.6 %) complained of moderate pain and 27 (10.6%) showed
      severe pain; 1 year after surgery, 11 patients (4.3 %) had persistent pain, and
      two of them were re-submitted to surgery. The lower incidence of chronic pain
      after nerve resection is statistically significant (0.6 vs. 4.3 % p = 0.0048);
      the incidence of moderate pain 1 month after the operation is also lower (11.3
      vs. 17.6 % p = 0.0097). In addition, among patients subjected to nerve resection
      there is a faster resolution of algetic symptomatology, over the course of a
      month; also noteworthy is the lower incidence of intense pain in the short-and
      medium-term (after 1 week, 11.8 vs. 2.6 % p = 0.0006 ; after 1 month, 10.6 vs.
      1.7 % p < 0.0001). CONCLUSIONS: Despite the apparent paradox of an higher tissue
      damage, elective neurectomy of selected segments of inguinal nerves, appears an
      effective technique in preventing chronic postherniorraphy pain, considering both
      the lower incidence and the faster resolution of painful symptomatology.

PMID- 24752248
TI  - Co-option of a photoperiodic growth-phase transition system during land plant
      evolution.
AB  - Photoperiodic control of the phase transition from vegetative to reproductive
      growth is critical for land plants. The GIGANTEA (GI) and FLAVIN-BINDING KELCH
      REPEAT F-BOX1 (FKF1) protein complex controls this process in angiosperms.
      However, little is known about how plants evolved this regulatory system. Here,
      we report that orthologues of GI and FKF1 are present in a basal plant, the
      liverwort Marchantia polymorpha, and describe the molecular interaction between
      their products. Knockout of either the GI or FKF1 orthologue completely abolishes
      the long-day-dependent growth-phase transition in M. polymorpha. Overexpression
      of either gene promotes growth-phase transition, even under short-day conditions.
      Introduction of the GI orthologue partially rescues the late-flowering phenotype
      of the Arabidopsis thaliana gi mutant. Our findings suggest that plants had
      already acquired the GI-FKF1 system to regulate growth-phase transition when they
      colonized land, and that this system was co-opted from gametophyte to sporophyte
      generation during evolution. 

PMID- 24752249
TI  - Rare mutations of CACNB2 found in autism spectrum disease-affected families alter
      calcium channel function.
AB  - Autism Spectrum Disorders (ASD) are complex neurodevelopmental diseases
      clinically defined by dysfunction of social interaction. Dysregulation of
      cellular calcium homeostasis might be involved in ASD pathogenesis, and genes
      coding for the L-type calcium channel subunits CaV1.2 (CACNA1C) and CaVbeta2
      (CACNB2) were recently identified as risk loci for psychiatric diseases. Here, we
      present three rare missense mutations of CACNB2 (G167S, S197F, and F240L) found
      in ASD-affected families, two of them described here for the first time (G167S
      and F240L). All these mutations affect highly conserved regions while being
      absent in a sample of ethnically matched controls. We suggest the mutations to be
      of physiological relevance since they modulate whole-cell Ba2+ currents through
      calcium channels when expressed in a recombinant system (HEK-293 cells). Two
      mutations displayed significantly decelerated time-dependent inactivation as well
      as increased sensitivity of voltage-dependent inactivation. In contrast, the
      third mutation (F240L) showed significantly accelerated time-dependent
      inactivation. By altering the kinetic parameters, the mutations are reminiscent
      of the CACNA1C mutation causing Timothy Syndrome, a Mendelian disease presenting
      with ASD. In conclusion, the results of our first-time biophysical
      characterization of these three rare CACNB2 missense mutations identified in ASD
      patients support the hypothesis that calcium channel dysfunction may contribute
      to autism. 

PMID- 24752250
TI  - Face age modulates gaze following in young adults.
AB  - Gaze-following behaviour is considered crucial for social interactions which are
      influenced by social similarity. We investigated whether the degree of
      similarity, as indicated by the perceived age of another person, can modulate
      gaze following. Participants of three different age-groups (18-25; 35-45; over
      65) performed an eye movement (a saccade) towards an instructed target while
      ignoring the gaze-shift of distracters of different age-ranges (6-10; 18-25; 35
      45; over 70). The results show that gaze following was modulated by the
      distracter face age only for young adults. Particularly, the over 70 year-old
      distracters exerted the least interference effect. The distracters of a similar
      age-range as the young adults (18-25; 35-45) had the most effect, indicating a
      blurred own-age bias (OAB) only for the young age group. These findings suggest
      that face age can modulate gaze following, but this modulation could be due to
      factors other than just OAB (e.g., familiarity). 

PMID- 24752251
TI  - Emergence of clinical Salmonella enterica serovar Typhimurium isolates with
      concurrent resistance to ciprofloxacin, ceftriaxone, and azithromycin.
AB  - Salmonella infection is an important public health issue for which the needs of
      antimicrobial treatment are increasing. A total of 546 human clinical S. enterica
      serovar Typhimurium isolates were recovered from patients in hospitals in China
      during the period of 2005 to ~ 2011. Twenty percent of the isolates exhibited
      resistance to ciprofloxacin, and 4% were resistant to ceftriaxone. Importantly,
      for the first time, 12 (2%) S. Typhimurium isolates resistant to both
      ciprofloxacin and ceftriaxone were recovered; among these 12 isolates, two were
      also resistant to azithromycin, and one was resistant to all other drugs tested.
      The combined effects of various transferrable extended-spectrum beta-lactamase
      determinants and a novel efflux-based ciprofloxacin resistance mechanism encoded
      by the mobile efflux gene oqxAB were responsible for the emergence of these
      extremely (highly) drug-resistant (XDR) S. Typhimurium isolates. The
      dissemination of resistance genes, such as those encoding ESBLs and the OqxAB
      pump, among Salmonella organisms will speed up the selection of XDR Salmonella,
      posing a huge threat to public health and Salmonella infection control.

PMID- 24752252
TI  - IncH-type plasmid harboring bla CTX-M-15, bla DHA-1, and qnrB4 genes recovered
      from animal isolates.
AB  - The whole sequence of plasmid pENVA carrying the extended-spectrum beta-lactamase
      gene blaCTX-M-15 was determined. It was identified from a series of clonally
      related Klebsiella pneumoniae sequence type 274 strains recovered from companion
      animals. This plasmid was 253,984 bp in size and harbored, in addition to blaCTX
      M-15, a large array of genes encoding resistance to many antibiotic molecules,
      including beta-lactams (blaTEM-1, blaDHA-1), aminoglycosides (aacA2, aadA1),
      tetracycline (tetA), quinolones (qnrB4), trimethoprim (dfrA15), and sulfonamides
      (two copies of sul1). In addition, genes encoding resistance to mercury,
      tellurium, nickel, and quaternary compounds were identified. It also carried
      genes encoding DNA damage protection and mutagenesis repair and a locus for a
      CRISPR system, which corresponds to an immune system involved in protection
      against bacteriophages and plasmids. Comparative analysis of the plasmid scaffold
      showed that it possessed a structure similar to that of only a single plasmid,
      which was pNDM-MAR encoding the carbapenemase NDM-1 and identified from human K.
      pneumoniae isolates. Both plasmids possessed two replicons, namely, those of
      IncFIB-like and IncHIB-like plasmids, which were significantly different from
      those previously characterized. The blaCTX-M-15 gene, together with the other
      antibiotic resistance genes, was part of a large module likely acquired through a
      transposition process. We characterized here a new plasmid type carrying the
      blaCTX-M-15 gene identified in a K. pneumoniae isolate of animal origin. The
      extent to which this plasmid type may spread efficiently and possibly further
      enhance the dissemination of blaCTX-M-15 among animal and human isolates remains
      to be determined. 

PMID- 24752253
TI  - Unacceptably high error rates in Vitek 2 testing of cefepime susceptibility in
      extended-spectrum-beta-lactamase-producing Escherichia coli.
AB  - While a lack of concordance is known between gold standard MIC determinations and
      Vitek 2, the magnitude of the discrepancy and its impact on treatment decisions
      for extended-spectrum-beta-lactamase (ESBL)-producing Escherichia coli are not.
      Clinical isolates of ESBL-producing E. coli were collected from blood, tissue,
      and body fluid samples from January 2003 to July 2009. Resistance genotypes were
      identified by PCR. Primary analyses evaluated the discordance between Vitek 2 and
      gold standard methods using cefepime susceptibility breakpoint cutoff values of
      8, 4, and 2 MUg/ml. The discrepancies in MICs between the methods were classified
      per convention as very major, major, and minor errors. Sensitivity, specificity,
      and positive and negative predictive values for susceptibility classifications
      were calculated. A total of 304 isolates were identified; 59% (179) of the
      isolates carried blaCTX-M, 47% (143) carried blaTEM, and 4% (12) carried blaSHV.
      At a breakpoint MIC of 8 MUg/ml, Vitek 2 produced a categorical agreement of
      66.8% and exhibited very major, major, and minor error rates of 23% (20/87
      isolates), 5.1% (8/157 isolates), and 24% (73/304), respectively. The
      sensitivity, specificity, and positive and negative predictive values for a
      susceptibility breakpoint of 8 MUg/ml were 94.9%, 61.2%, 72.3%, and 91.8%,
      respectively. The sensitivity, specificity, and positive and negative predictive
      values for a susceptibility breakpoint of 2 MUg/ml were 83.8%, 65.3%, 41%, and
      93.3%, respectively. Vitek 2 results in unacceptably high error rates for
      cefepime compared to those of agar dilution for ESBL-producing E. coli.
      Clinicians should be wary of making treatment decisions on the basis of Vitek 2
      susceptibility results for ESBL-producing E. coli. 

PMID- 24752254
TI  - Escherichia coli sequence type 354 coproducing CMY-2 cephalosporinase and RmtE
      16S rRNA methyltransferase.

PMID- 24752255
TI  - The mecA homolog mecC confers resistance against beta-lactams in Staphylococcus
      aureus irrespective of the genetic strain background.
AB  - In staphylococci, methicillin resistance is mediated by mecA-encoded penicillin
      binding protein 2a (PBP2a), which has a low affinity for beta-lactams. Recently,
      a novel PBP2a homolog was described as being encoded by mecC, which shares only
      70% similarity to mecA. To prove that mecC is the genetic determinant that
      confers methicillin resistance in Staphylococcus aureus, a mecC knockout strain
      was generated. The S. aureus DeltamecC strain showed considerably reduced
      oxacillin and cefoxitin MICs (0.25 and 4 MUg/ml, respectively) compared to those
      of the corresponding wild-type methicillin-resistant S. aureus (MRSA) strain (8
      and 16 MUg/ml, respectively). Complementing the mutant in trans with wild-type
      mecC restored the resistance to oxacillin and cefoxitin. By expressing mecC and
      mecA in different S. aureus clonal lineages, we found that mecC mediates
      resistance irrespective of the genetic strain background, yielding oxacillin and
      cefoxitin MIC values comparable to those with mecA. In addition, we showed that
      mecC expression is inducible by oxacillin, which supports the assumption that a
      functional beta-lactam-dependent regulatory system is active in MRSA strains
      possessing staphylococcal cassette chromosome mec (SCCmec) type XI. In summary,
      we showed that mecC is inducible by oxacillin and mediates beta-lactam resistance
      in SCCmec type XI-carrying strains as well as in different S. aureus genetic
      backgrounds. Furthermore, our results could explain the comparatively low MICs
      for clinical mecC-harboring S. aureus isolates. 

PMID- 24752256
TI  - Synergistic activity of the tyrocidines, antimicrobial cyclodecapeptides from
      Bacillus aneurinolyticus, with amphotericin B and caspofungin against Candida
      albicans biofilms.
AB  - Tyrocidines are cationic cyclodecapeptides from Bacillus aneurinolyticus that are
      characterized by potent antibacterial and antimalarial activities. In this study,
      we show that various tyrocidines have significant activity against planktonic
      Candida albicans in the low-micromolar range. These tyrocidines also prevented C.
      albicans biofilm formation in vitro. Studies with the membrane-impermeable dye
      propidium iodide showed that the tyrocidines disrupt the membrane integrity of
      mature C. albicans biofilm cells. This membrane activity correlated with the
      permeabilization and rapid lysis of model fungal membranes containing
      phosphatidylcholine and ergosterol (70:30 ratio) induced by the tyrocidines. The
      tyrocidines exhibited pronounced synergistic biofilm-eradicating activity in
      combination with two key antifungal drugs, amphotericin B and caspofungin. Using
      a Caenorhabditis elegans infection model, we found that tyrocidine A potentiated
      the activity of caspofungin. Therefore, tyrocidines are promising candidates for
      further research as antifungal drugs and as agents for combinatorial treatment. 

PMID- 24752257
TI  - Plasmid carriage of bla NDM-1 in clinical Acinetobacter baumannii isolates from
      India.
AB  - NDM-1 probably emerged in Acinetobacter species prior to its dissemination among
      Enterobacteriaceae, and NDM-1-like enzymes are increasingly reported in
      Acinetobacter species. Here, we report on the genetic context of blaNDM-1 in the
      earliest known NDM-1-producing organisms, clinical isolates of Acinetobacter from
      India in 2005. These strains harbor blaNDM-1 plasmids of different sizes. The
      gene is associated with the remnants of the Tn125 transposon normally associated
      with blaNDM-1 in Acinetobacter spp. The transposon has been disrupted by the IS26
      insertion and subsequent movement events. 

PMID- 24752258
TI  - In vitro amphotericin B susceptibility of Malassezia pachydermatis determined by
      the CLSI broth microdilution method and Etest using lipid-enriched media.
AB  - We determined the in vitro amphotericin B susceptibility of 60 Malassezia
      pachydermatis isolates by the CLSI broth microdilution method and the Etest using
      lipid-enriched media. All isolates were susceptible at MICs of <= 1 MUg/ml,
      confirming the high activity of amphotericin B against this yeast species.
      Overall, the essential agreement between the tested methods was high (80% and
      96.7% after 48 h and 72 h, respectively), and all discrepancies were regarded as
      nonsubstantial.

PMID- 24752259
TI  - Complete nucleotide sequence of two multidrug-resistant IncR plasmids from
      Klebsiella pneumoniae.
AB  - We report here the complete nucleotide sequence of two IncR replicons encoding
      multidrug resistance determinants, including beta-lactam (blaDHA-1, blaSHV-12),
      aminoglycoside (aphA1, strA, strB), and fluoroquinolone (qnrB4, aac6'-1b-cr)
      resistance genes. The plasmids have backbones that are similar to each other,
      including the replication and stability systems, and contain a wide variety of
      transposable elements carrying known antibiotic resistance genes. This study
      confirms the increasing clinical importance of IncR replicons as resistance gene
      carriers. 

PMID- 24752260
TI  - Population pharmacokinetic analysis of piperacillin in burn patients.
AB  - Piperacillin in combination with tazobactam, a beta-lactamase inhibitor, is a
      commonly used intravenous antibiotic for the empirical treatment of infection in
      intensive care patients, including burn patients. The purpose of this study was
      to develop a population pharmacokinetic (PK) model for piperacillin in burn
      patients and to predict the probability of target attainment (PTA) using MICs and
      concentrations simulated from the PK model. Fifty burn patients treated with
      piperacillin-tazobactam were enrolled. Piperacillin-tazobactam was administered
      via infusion for approximately 30 min at a dose of 4.5 g (4 g piperacillin and
      0.5 g tazobactam) every 8 h. Blood samples were collected just prior to and at 1,
      2, 3, 4, and 6 h after the end of the infusion at steady state. The population PK
      model of piperacillin was developed using NONMEM. A two-compartment first-order
      elimination PK model was finally chosen. The covariates included were creatinine
      clearance (CLCR), day after burn injury (DAI), and sepsis. The final PK
      parameters were clearance (liters/h) (equal to 16.6 * [CLCR/132] + DAI * [
      0.0874]), central volume (liters) (equal to 25.3 + 14.8 * sepsis [0 for the
      absence or 1 for the presence of sepsis]), peripheral volume (liters) (equal to
      16.1), and intercompartmental clearance (liters/h) (equal to 0.636). The
      clearance and volume of piperacillin were higher than those reported in patients
      without burns, and the terminal half-life and PTA decreased with the increased
      CLCR. Our PK model suggests that higher daily doses or longer durations of
      infusion of piperacillin should be considered, especially for burn patients with
      a CLCR of >= 160 ml/min.

PMID- 24752261
TI  - IS1R-mediated plasticity of IncL/M plasmids leads to the insertion of bla OXA-48
      into the Escherichia coli Chromosome.
AB  - The OXA-48 carbapenemase is mainly encoded by ~ 62-kb IncL/M plasmids. However,
      chromosome-mediated genes have been observed in Escherichia coli isolates. In
      this work, we investigated the genetic environment of OXA-48 in members of the
      family Enterobacteriaceae (n = 22) to understand how the OXA-48-encoding gene is
      transferred into the E. coli chromosome. The OXA-48-encoding gene was located
      within intact Tn1999.2 transposons in the ~ 62-kb plasmids or within a truncated
      variant of Tn1999.2 for the OXA-48-encoding genes located in the chromosomes of
      E. coli bacteria. The analysis of the Tn1999.2 genetic environment revealed an
      inverted orientation of the transposon in five ~ 62-kb plasmids (5/14 [35%]) and
      in all chromosome inserts (n = 8). The sequencing of pRA35 plasmid showed that
      this orientation of Tn1999.2 and the acquisition of an IS1R insertion sequence
      generated a 21.9-kb IS1R-based composite transposon encoding OXA-48 and
      designated Tn6237. The sequencing of a chromosomal insert encoding OXA-48 also
      revealed this new transposon in the E. coli chromosome. PCR mapping showed the
      presence of this element in all strains harboring an OXA-48-encoding chromosomal
      insert. However, different insertion sites of this transposon were observed in
      the E. coli chromosome. Overall, these findings indicate a plasticity of the OXA
      48 genetic environment mediated by IS1R insertion sequences. The insertion
      sequences can induce the transfer of the OXA-encoding gene into E. coli
      chromosomes and thereby promote its persistence and expression at low levels.

PMID- 24752262
TI  - Copper complexation screen reveals compounds with potent antibiotic properties
      against methicillin-resistant Staphylococcus aureus.
AB  - Macrophages take advantage of the antibacterial properties of copper ions in the
      killing of bacterial intruders. However, despite the importance of copper for
      innate immune functions, coordinated efforts to exploit copper ions for
      therapeutic interventions against bacterial infections are not yet in place. Here
      we report a novel high-throughput screening platform specifically developed for
      the discovery and characterization of compounds with copper-dependent
      antibacterial properties toward methicillin-resistant Staphylococcus aureus
      (MRSA). We detail how one of the identified compounds, glyoxal-bis(N4
      methylthiosemicarbazone) (GTSM), exerts its potent strictly copper-dependent
      antibacterial properties on MRSA. Our data indicate that the activity of the GTSM
      copper complex goes beyond the general antibacterial effects of accumulated
      copper ions and suggest that, in contrast to prevailing opinion, copper complexes
      can indeed exhibit species- and target-specific activities. Based on experimental
      evidence, we propose that copper ions impose structural changes upon binding to
      the otherwise inactive GTSM ligand and transfer antibacterial properties to the
      chelate. In turn, GTSM determines target specificity and utilizes a redox
      sensitive release mechanism through which copper ions are deployed at or in close
      proximity to a putative target. According to our proof-of-concept screen, copper
      activation is not a rare event and even extends to already established drugs.
      Thus, copper-activated compounds could define a novel class of anti-MRSA agents
      that amplify copper-dependent innate immune functions of the host. To this end,
      we provide a blueprint for a high-throughput drug screening campaign which
      considers the antibacterial properties of copper ions at the host-pathogen
      interface. 

PMID- 24752263
TI  - In vitro and in vivo biological effects of novel arylimidamide derivatives
      against Trypanosoma cruzi.
AB  - Chagas disease (CD), a neglected tropical disease caused by Trypanosoma cruzi,
      remains a serious public health problem in several Latin American countries. The
      available chemotherapies for CD have limited efficacy and exhibit undesirable
      side effects. Aromatic diamidines and arylimidamides (AIAs) have shown broad
      spectrum activity against intracellular parasites, including T. cruzi. Therefore,
      our aim was to evaluate the biological activity of eight novel AIAs (16DAP002,
      16SAB079, 18SAB075, 23SMB022, 23SMB026, 23SMB054, 26SMB070, and 27SMB009) against
      experimental models of T. cruzi infection in vitro and in vivo. Our data show
      that none of the compounds induced a loss of cellular viability up to 32 MUM. Two
      AIAs, 18SAB075 and 16DAP002, exhibited good in vitro activity against different
      parasite strains (Y and Tulahuen) and against the two relevant forms of the
      parasite for mammalian hosts. Due to the excellent selective indexes of 18SAB075,
      this AIA was moved to in vivo tests for acute toxicity and parasite efficacy;
      nontoxic doses (no-observed-adverse-effect level [NOAEL], 50 mg/kg) were employed
      in the tests for parasite efficacy. In experimental models of acute T. cruzi
      infection, 18SAB075 reduced parasitemia levels only up to 50% and led to 40%
      protection against mortality (at 5 mg/kg of body weight), being less effective
      than the reference drug, benznidazole. 

PMID- 24752264
TI  - Strain types and antimicrobial resistance patterns of Clostridium difficile
      isolates from the United States, 2011 to 2013.
AB  - We determined the PCR ribotypes and antimicrobial susceptibility patterns of 508
      toxigenic Clostridium difficile isolates collected between 2011 and 2013 from 32
      U.S. hospitals. Of the 29 PCR ribotypes identified, the 027 strain type was the
      most common (28.1%), although the rates varied by geographic region. Ribotype
      014/020 isolates appear to be emerging. Clindamycin and moxifloxacin resistances
      (36.8% and 35.8%, respectively) were the most frequent resistance phenotypes
      observed. Reduced susceptibility to vancomycin was observed in 39.1% of 027
      isolates. 

PMID- 24752265
TI  - Characteristics of Escherichia coli sequence type 131 isolates that produce
      extended-spectrum beta-lactamases: global distribution of the H30-Rx sublineage.
AB  - We designed a study to describe the characteristics of sequence type 131 (ST131)
      lineages, including the H30-Rx sublineage, among a global collection of extended
      spectrum beta-lactamase (ESBL)-producing Escherichia coli isolates from 9
      countries collected from 2000 to 2011. A total of 240 nonrepeat isolates from
      Canada, the United States, Brazil, the Netherlands, France, the United Arab
      Emirates (UAE), India, South Africa, and New Zealand were included. Established
      PCR, sequencing, and typing methods were used to define ST131 lineages, H30 and
      H30-Rx phylogenetic groups, gyrA and parC mutations, virotypes, and plasmid
      mediated quinolone resistance determinants. The majority of the isolates produced
      CTX-M-15 with aac(6')-lb-cr, belonged to phylogenetic group B2, and were positive
      for the H30 lineage with the gyrA1AB and parC1aAB mutations. ST131 showed 15
      distinct pulsotypes; 43% of the isolates belonged to four pulsotypes, with a
      global distribution. Seventy-five percent of the ST131 isolates belonged to H30
      Rx; this sublineage was present in all the countries and was associated with
      multidrug resistance, blaCTX-M-15, aac(6')-lb-cr, and virotypes A and C. The H41
      lineage was negative for the ST131 pabB allele-specific PCR. The multidrug
      resistant H30-Rx sublineage poses an important public health threat due to its
      global distribution, association with virotype C, and high prevalence among ST131
      isolates that produce CTX-M-15. 

PMID- 24752266
TI  - Akt inhibitor MK2206 prevents influenza pH1N1 virus infection in vitro.
AB  - The influenza pH1N1 virus caused a global flu pandemic in 2009 and continues
      manifestation as a seasonal virus. Better understanding of the virus-host cell
      interaction could result in development of better prevention and treatment
      options. Here we show that the Akt inhibitor MK2206 blocks influenza pH1N1 virus
      infection in vitro. In particular, at noncytotoxic concentrations, MK2206 alters
      Akt signaling and inhibits endocytic uptake of the virus. Interestingly, MK2206
      is unable to inhibit H3N2, H7N9, and H5N1 viruses, indicating that pH1N1 evolved
      specific requirements for efficient infection. Thus, Akt signaling could be
      exploited further for development of better therapeutics against pH1N1 virus. 

PMID- 24752269
TI  - Cohort study of the impact of time to antibiotic administration on mortality in
      patients with febrile neutropenia.
AB  - The time to antibiotic administration (TTA) has been proposed as a quality-of
      care measure in febrile neutropenia (FN); however, few data regarding the impact
      of the TTA on the mortality of adult cancer patients with FN are available. The
      objective of this study was to determine whether the TTA is a predictor of
      mortality in adult cancer patients with FN. A prospective cohort study of all
      consecutive cases of FN, evaluated from October 2009 to August 2011, at a single
      tertiary referral hospital in southern Brazil was performed. The TTA was assessed
      as a predictive factor for mortality within 28 days of FN onset using the Cox
      proportional hazards model. Kaplan-Meier curves were used for an assessment of
      the mortality rates according to different TTAs; the log-rank test was used for
      between-group comparisons. In total, 307 cases of FN (169 subjects) were
      evaluated. During the study period, there were 29 deaths. In a Cox regression
      analysis, the TTA was independently associated with mortality within 28 days
      (hazard ratio [HR], 1.18; 95% confidence interval [CI], 1.10 to 1.26); each
      increase of 1 h in the TTA raised the risk of mortality within 28 days by 18%.
      Patients with FN episodes with a TTA of <= 30 min had lower 28-day mortality
      rates than those with a TTA of between 31 min and 60 min (3.0% versus 18.1%; log
      rank P = 0.0002). Early antibiotic administration was associated with higher
      survival rates in the context of FN. Efforts should be made to ensure that FN
      patients receive effective antibiotic therapy as soon as possible. A target of 30
      min to the TTA should be adopted for cancer patients with FN.

PMID- 24752267
TI  - Art-175 is a highly efficient antibacterial against multidrug-resistant strains
      and persisters of Pseudomonas aeruginosa.
AB  - Artilysins constitute a novel class of efficient enzyme-based antibacterials.
      Specifically, they covalently combine a bacteriophage-encoded endolysin, which
      degrades the peptidoglycan, with a targeting peptide that transports the
      endolysin through the outer membrane of Gram-negative bacteria. Art-085, as well
      as Art-175, its optimized homolog with increased thermostability, are each
      composed of the sheep myeloid 29-amino acid (SMAP-29) peptide fused to the KZ144
      endolysin. In contrast to KZ144, Art-085 and Art-175 pass the outer membrane and
      kill Pseudomonas aeruginosa, including multidrug-resistant strains, in a rapid
      and efficient (~ 5 log units) manner. Time-lapse microscopy confirms that Art-175
      punctures the peptidoglycan layer within 1 min, inducing a bulging membrane and
      complete lysis. Art-175 is highly refractory to resistance development by
      naturally occurring mutations. In addition, the resistance mechanisms against 21
      therapeutically used antibiotics do not show cross-resistance to Art-175. Since
      Art-175 does not require an active metabolism for its activity, it has a superior
      bactericidal effect against P. aeruginosa persisters (up to >4 log units compared
      to that of the untreated controls). In summary, Art-175 is a novel antibacterial
      that is well suited for a broad range of applications in hygiene and veterinary
      and human medicine, with a unique potential to target persister-driven chronic
      infections.

PMID- 24752268
TI  - Polymorphisms in Pfmdr1, Pfcrt, and Pfnhe1 genes are associated with reduced in
      vitro activities of quinine in Plasmodium falciparum isolates from western Kenya.
AB  - In combination with antibiotics, quinine is recommended as the second-line
      treatment for uncomplicated malaria, an alternative first-line treatment for
      severe malaria, and for treatment of malaria in the first trimester of pregnancy.
      Quinine has been shown to have frequent clinical failures, and yet the mechanisms
      of action and resistance have not been fully elucidated. However, resistance is
      linked to polymorphisms in multiple genes, including multidrug resistance 1
      (Pfmdr1), the chloroquine resistance transporter (Pfcrt), and the sodium/hydrogen
      exchanger gene (Pfnhe1). Here, we investigated the association between in vitro
      quinine susceptibility and genetic polymorphisms in Pfmdr1codons 86 and 184,
      Pfcrt codon 76, and Pfnhe1 ms4760 in 88 field isolates from western Kenya. In
      vitro activity was assessed based on the drug concentration that inhibited 50% of
      parasite growth (the IC50), and parasite genetic polymorphisms were determined
      from DNA sequencing. Data revealed there were significant associations between
      polymorphism in Pfmdr1-86Y, Pfmdr1-184F, or Pfcrt-76T and quinine susceptibility
      (P < 0.0001 for all three associations). Eighty-two percent of parasites
      resistant to quinine carried mutant alleles at these codons (Pfmdr1-86Y, Pfmdr1
      184F, and Pfcrt-76T), whereas 74% of parasites susceptible to quinine carried the
      wild-type allele (Pfmdr1-N86, Pfmdr1-Y184, and Pfcrt-K76, respectively). In
      addition, quinine IC50 values for parasites with Pfnhe1 ms4760 3 DNNND repeats
      were significantly higher than for those with 1 or 2 repeats (P = 0.033 and P =
      0.0043, respectively). Clinical efficacy studies are now required to confirm the
      validity of these markers and the importance of parasite genetic background. 

PMID- 24752270
TI  - Relationship between time to clinical response and outcomes among Pneumonia
      Outcomes Research Team (PORT) risk class III and IV hospitalized patients with
      community-acquired pneumonia who received ceftriaxone and azithromycin.
AB  - Recent Food and Drug Administration (FDA) guidance endorses the use of an early
      clinical response endpoint as the primary outcome for community-acquired
      bacterial pneumonia (CABP) trials. While antibiotics will now be approved for
      CABP, in practice they will primarily be used to treat patients with community
      acquired pneumonia (CAP). More importantly, it is unclear how achievement of the
      new FDA CABP early response endpoint translates into clinically applicable real
      world outcomes for patients with CAP. To address this, a retrospective cohort
      study was conducted among adult patients who received ceftriaxone and
      azithromycin for CAP of Pneumonia Outcomes Research Team (PORT) risk class III
      and IV at an academic medical center. The clinical response was defined as
      clinical stability for 24 h with improvement in at least one pneumonia symptom
      and with no symptom worsening. A classification and regression tree (CART) was
      used to determine the delay in response time, measured in days, associated with
      the greatest risk of a prolonged hospital length of stay (LOS) and adverse
      outcomes (in-hospital mortality or 30-day CAP-related readmission). A total of
      250 patients were included. On average, patients were discharged 2 days following
      the achievement of a clinical response. In the CART analysis, adverse clinical
      outcomes were higher among day 5 nonresponders than those who responded by day 5
      (22.4% versus 6.9%, P = 0.001). The findings from this study indicate that time
      to clinical response, as defined by the recent FDA guidance, is a reasonable
      prognostic indicator of real-world effectiveness outcomes among hospitalized PORT
      risk class III and IV patients with CAP who received ceftriaxone and
      azithromycin.

PMID- 24752271
TI  - A conserved hydrogen-bonding network of P2 bis-tetrahydrofuran-containing HIV-1
      protease inhibitors (PIs) with a protease active-site amino acid backbone aids in
      their activity against PI-resistant HIV.
AB  - In the present study, GRL008, a novel nonpeptidic human immunodeficiency virus
      type 1 (HIV-1) protease inhibitor (PI), and darunavir (DRV), both of which
      contain a P2-bis-tetrahydrofuranyl urethane (bis-THF) moiety, were found to exert
      potent antiviral activity (50% effective concentrations [EC50s], 0.029 and 0.002
      MUM, respectively) against a multidrug-resistant clinical isolate of HIV-1
      (HIVA02) compared to ritonavir (RTV; EC50, >1.0 MUM) and tipranavir (TPV; EC50,
      0.364 MUM). Additionally, GRL008 showed potent antiviral activity against an HIV
      1 variant selected in the presence of DRV over 20 passages (HIVDRV(R)P20), with a
      2.6-fold increase in its EC50 (0.097 MUM) compared to its corresponding EC50
      (0.038 MUM) against wild-type HIV-1NL4-3 (HIVWT). Based on X-ray crystallographic
      analysis, both GRL008 and DRV showed strong hydrogen bonds (H-bonds) with the
      backbone-amide nitrogen/carbonyl oxygen atoms of conserved active-site amino
      acids G27, D29, D30, and D30' of HIVA02 protease (PRA02) and wild-type PR in
      their corresponding crystal structures, while TPV lacked H-bonds with G27 and
      D30' due to an absence of polar groups. The P2' thiazolyl moiety of RTV showed
      two conformations in the crystal structure of the PRA02-RTV complex, one of which
      showed loss of contacts in the S2' binding pocket of PRA02, supporting RTV's
      compromised antiviral activity (EC50, >1 MUM). Thus, the conserved H-bonding
      network of P2-bis-THF-containing GRL008 with the backbone of G27, D29, D30, and
      D30' most likely contributes to its persistently greater antiviral activity
      against HIVWT, HIVA02, and HIVDRV(R)P20. 

PMID- 24752272
TI  - Activity of potent and selective host defense peptide mimetics in mouse models of
      oral candidiasis.
AB  - There is a strong need for new broadly active antifungal agents for the treatment
      of oral candidiasis that not only are active against many species of Candida,
      including drug-resistant strains, but also evade microbial countermeasures which
      may lead to resistance. Host defense peptides (HDPs) can provide a foundation for
      the development of such agents. Toward this end, we have developed fully
      synthetic, small-molecule, nonpeptide mimetics of the HDPs that improve safety
      and other pharmaceutical properties. Here we describe the identification of
      several HDP mimetics that are broadly active against C. albicans and other
      species of Candida, rapidly fungicidal, and active against yeast and hyphal
      cultures and that exhibit low cytotoxicity for mammalian cells. Importantly,
      specificity for Candida over commensal bacteria was also evident, thereby
      minimizing potential damage to the endogenous microbiome which otherwise could
      favor fungal overgrowth. Three compounds were tested as topical agents in two
      different mouse models of oral candidiasis and were found to be highly active.
      Following single-dose administrations, total Candida burdens in tongues of
      infected animals were reduced up to three logs. These studies highlight the
      potential of HDP mimetics as a new tool in the antifungal arsenal for the
      treatment of oral candidiasis. 

PMID- 24752273
TI  - Lack of antimicrobial bactericidal activity in Mycobacterium abscessus.
AB  - Antibiotic therapy of infections caused by the emerging pathogen Mycobacterium
      abscessus is challenging due to the organism's natural resistance toward most
      clinically available antimicrobials. We investigated the bactericidal activity of
      antibiotics commonly administered in M. abscessus infections in order to better
      understand the poor therapeutic outcome. Time-kill curves were generated for
      clinical M. abscessus isolates, Mycobacterium smegmatis, and Escherichia coli by
      using antibiotics commonly categorized as bactericidal (amikacin and
      moxifloxacin) or bacteriostatic (tigecycline and linezolid). In addition, the
      impact of aminoglycoside-modifying enzymes on the mode of action of substrate and
      nonsubstrate aminoglycosides was studied by using M. smegmatis as a model
      organism. While amikacin and moxifloxacin were bactericidal against E. coli, none
      of the tested compounds showed bactericidal activity against M. abscessus.
      Further mechanistic investigations of the mode of action of aminoglycosides in M.
      smegmatis revealed that the bactericidal activity of tobramycin and gentamicin
      was restored by disruption of the chromosomal aac(2') gene in the mycobacterial
      genome. The lack of bactericidal antibiotics in currently recommended treatment
      regimens provides a reasonable explanation for the poor therapeutic outcome in M.
      abscessus infection. Our findings suggest that chromosomally encoded drug
      modifying enzymes play an important role in the lack of aminoglycoside
      bactericidal activity against rapidly growing mycobacteria. 

PMID- 24752274
TI  - Antifungal susceptibilities of Candida isolates causing bloodstream infections at
      a medical center in Taiwan, 2009-2010.
AB  - We used the Sensititre YeastOne (SYO) method (Trek Diagnostic Systems) to
      determine the MICs of nine antifungal agents against 474 nonduplicate blood
      Candida isolates. The MIC results were interpreted according to updated clinical
      breakpoints (CBPs) recommended by the Clinical and Laboratory Standards Institute
      (CLSI; document M27-S4) or epidemiology cutoff values (ECVs). The rates of
      fluconazole susceptibility were 99.2% (234/236) in Candida albicans, 86.7%
      (85/98) in C. tropicalis, and 97.7% (42/43) in C. parapsilosis. Among the 77
      isolates of C. glabrata, 90.9% showed dose-dependent susceptibility (S-DD) to
      fluconazole. Nearly all isolates of C. albicans, C. parapsilosis, and C. krusei
      were susceptible to voriconazole; however, rates of voriconazole susceptibility
      were 78.6% in C. tropicalis. Few isolates of C. albicans (n = 5; 2.1%) and C.
      glabrata (n = 3; 3.9%), no isolates of C. parapsilosis, C. krusei, and C.
      guilliermondii, but 62.2% (n = 51) of C. tropicalis isolates were non-wild type
      for posaconazole susceptibility. For itraconazole susceptibility, 98.3% of C.
      albicans isolates were wild type, and 3.9% (n = 3) of C. glabrata isolates were
      non-wild type. Almost all of the isolates tested (>97% for all species) were
      susceptible to both micafungin and anidulafungin. All isolates tested were found
      to be wild type for amphotericin B susceptibility, with MICs of <1 MUg/ml.
      Further evaluation is needed to establish CBPs of antifungal agents by the 24-h
      SYO method for the management of patients with candidemia or other invasive
      candida infections.

PMID- 24752275
TI  - Potentiation effects of amikacin and fosfomycin against selected amikacin
      nonsusceptible Gram-negative respiratory tract pathogens.
AB  - The amikacin-fosfomycin inhalation system (AFIS) is a combination of 2
      antibiotics and an in-line nebulizer delivery system that is being developed for
      adjunctive treatment of pneumonia caused by Gram-negative organisms in patients
      on mechanical ventilation. AFIS consists of a combination of amikacin and
      fosfomycin solutions at a 5:2 ratio (amikacin, 3 ml at 100 mg/ml; fosfomycin, 3
      ml at 40 mg/ml) and the PARI Investigational eFlow Inline System. In this
      antibiotic potentiation study, the antimicrobial activities of amikacin and
      fosfomycin, alone and in a 5:2 combination, were assessed against 62 Gram
      negative pathogens from a worldwide antimicrobial surveillance collection
      (SENTRY). The amikacin MICs for 62 isolates of Acinetobacter baumannii,
      Pseudomonas aeruginosa, and Klebsiella pneumoniae were >=32 MUg/ml (intermediate
      or resistant according to the Clinical and Laboratory Standards Institute [CLSI];
      resistant according to the European Committee on Antimicrobial Susceptibility
      Testing [EUCAST]). Each isolate was tested against amikacin (0.25 to 1,024
      MUg/ml), fosfomycin (0.1 to 409.6 MUg/ml), and amikacin-fosfomycin (at a 5:2
      ratio) using CLSI reference agar dilution methods. The median MIC values for
      amikacin and fosfomycin against the 62 isolates each decreased 2-fold with the
      amikacin-fosfomycin (5:2) combination from that with either antibiotic alone.
      Interactions between amikacin and fosfomycin differed by isolate and ranged from
      no detectable interaction to high potentiation. The amikacin-fosfomycin (5:2)
      combination reduced the amikacin concentration required to inhibit all 62
      isolates from >1,024 to <= 256 MUg/ml and reduced the required fosfomycin
      concentration from 204.8 to 102.4 MUg/ml. These results support continued
      development of the amikacin-fosfomycin combination for aerosolized
      administration, where high drug levels can be achieved.

PMID- 24752276
TI  - Amikacin-fosfomycin at a five-to-two ratio: characterization of mutation rates in
      microbial strains causing ventilator-associated pneumonia and interactions with
      commonly used antibiotics.
AB  - The amikacin-fosfomycin inhalation system (AFIS), a combination of antibiotics
      administered with an in-line nebulizer delivery system, is being developed for
      adjunctive treatment of ventilator-associated pneumonia (VAP). The in vitro
      characterization of amikacin-fosfomycin (at a 5:2 ratio) described here included
      determining resistance selection rates for pathogens that are representative of
      those commonly associated with VAP (including multidrug-resistant strains) and
      evaluating interactions with antibiotics commonly used intravenously to treat
      VAP. Spontaneous resistance to amikacin-fosfomycin (5:2) was not observed for
      most strains tested (n, 10/14). Four strains had spontaneously resistant colonies
      (frequencies, 4.25 * 10(-8) to 3.47 * 10(-10)), for which amikacin-fosfomycin
      (5:2) MICs were 2- to 8-fold higher than those for the original strains. After 7
      days of serial passage, resistance (>4-fold increase over the baseline MIC)
      occurred in fewer strains (n, 4/14) passaged in the presence of amikacin
      fosfomycin (5:2) than with either amikacin (n, 7/14) or fosfomycin (n, 12/14)
      alone. Interactions between amikacin-fosfomycin (5:2) and 10 comparator
      antibiotics in checkerboard testing against 30 different Gram-positive or Gram
      negative bacterial strains were synergistic (fractional inhibitory concentration
      [FIC] index, <= 0.5) for 6.7% (n, 10/150) of combinations tested. No antagonism
      was observed. Synergy was confirmed by time-kill methodology for amikacin
      fosfomycin (5:2) plus cefepime (against Escherichia coli), aztreonam (against
      Pseudomonas aeruginosa), daptomycin (against Enterococcus faecalis), and
      azithromycin (against Staphylococcus aureus). Amikacin-fosfomycin (5:2) was
      bactericidal at 4-fold the MIC for 7 strains tested. The reduced incidence of
      development of resistance to amikacin-fosfomycin (5:2) compared with that for
      amikacin or fosfomycin alone, and the lack of negative interactions with commonly
      used intravenous antibiotics, further supports the development of AFIS for the
      treatment of VAP.

PMID- 24752277
TI  - The low keratin affinity of efinaconazole contributes to its nail penetration and
      fungicidal activity in topical onychomycosis treatment.
AB  - Onychomycosis is a common fungal nail disease that is difficult to treat
      topically due to the deep location of the infection under the densely keratinized
      nail plate. Keratin affinity of topical drugs is an important physicochemical
      property impacting therapeutic efficacy. To be effective, topical drugs must
      penetrate the nail bed and retain their antifungal activity within the nail
      matrix, both of which are adversely affected by keratin binding. We investigated
      these properties for efinaconazole, a new topical antifungal for onychomycosis,
      compared with those of the existing topical drugs ciclopirox and amorolfine. The
      efinaconazole free-drug concentration in keratin suspensions was 14.3%,
      significantly higher than the concentrations of ciclopirox and amorolfine, which
      were 0.7% and 1.9%, respectively (P < 0.001). Efinaconazole was released from
      keratin at a higher proportion than in the reference drugs, with about half of
      the remaining keratin-bound efinaconazole removed after washing. In single-dose
      in vitro studies, efinaconazole penetrated full-thickness human nails into the
      receptor phase and also inhibited the growth of Trichophyton rubrum under the
      nail. In the presence of keratin, efinaconazole exhibited fungicidal activity
      against Trichophyton mentagrophytes comparable to that of amorolfine and superior
      to that of ciclopirox. In a guinea pig onychomycosis model with T. mentagrophytes
      infection, an efinaconazole solution significantly decreased nail fungal burden
      compared to that of ciclopirox and amorolfine lacquers (P < 0.01). These results
      suggest that the high nail permeability of efinaconazole and its potent
      fungicidal activity in the presence of keratin are related to its low keratin
      affinity, which may contribute to its efficacy in onychomycosis. 

PMID- 24752278
TI  - Pharmacokinetics-pharmacodynamics of the helicase-primase inhibitor pritelivir
      following treatment of wild-type or pritelivir-resistant virus infection in a
      murine herpes simplex virus 1 infection model.
AB  - Herpes simplex virus (HSV) infections can cause considerable morbidity.
      Transmission of HSV-2 has become a major health concern, since it has been shown
      to promote transmission of other sexually transmitted diseases. Pritelivir
      (AIC316, BAY 57-1293) belongs to a new class of HSV antiviral compounds, the
      helicase-primase inhibitors, which have a mode of action that is distinct from
      that of antiviral nucleoside analogues currently in clinical use. Analysis of
      pharmacokinetic-pharmacodynamic parameters is a useful tool for the selection of
      appropriate doses in clinical trials, especially for compounds belonging to new
      classes for which no or only limited data on therapeutic profiles are available.
      For this purpose, the effective dose of pritelivir was determined in a
      comprehensive mouse model of HSV infection. Corresponding plasma concentrations
      were measured, and exposures were compared with efficacious concentrations
      derived from cell cultures. The administration of pritelivir at 10 mg/kg of body
      weight once daily for 4 days completely suppressed any signs of HSV infection in
      the animals. Associated plasma concentrations adjusted for protein binding stayed
      above the cell culture 90% effective concentration (EC90) for HSV-1 for almost
      the entire dosing interval. Interestingly, by increasing the dose 6-fold and
      prolonging the treatment duration to 8 days, it was possible to treat mice
      infected with an approximately 30-fold pritelivir-resistant but fully pathogenic
      HSV-1 virus. Corresponding plasma concentrations exceeded the EC90 of this mutant
      for <8 h, indicating that even suboptimal exposure to pritelivir is sufficient to
      achieve antiviral efficacy, possibly augmented by other factors such as the
      immune system. 

PMID- 24752279
TI  - Levels of germination proteins in Bacillus subtilis dormant, superdormant, and
      germinating spores.
AB  - Bacterial endospores exhibit extreme resistance to most conditions that rapidly
      kill other life forms, remaining viable in this dormant state for centuries or
      longer. While the majority of Bacillus subtilis dormant spores germinate rapidly
      in response to nutrient germinants, a small subpopulation termed superdormant
      spores are resistant to germination, potentially evading antibiotic and/or
      decontamination strategies. In an effort to better understand the underlying
      mechanisms of superdormancy, membrane-associated proteins were isolated from
      populations of B. subtilis dormant, superdormant, and germinated spores, and the
      relative abundance of 11 germination-related proteins was determined using
      multiple-reaction-monitoring liquid chromatography-mass spectrometry assays.
      GerAC, GerKC, and GerD were significantly less abundant in the membrane fractions
      obtained from superdormant spores than those derived from dormant spores. The
      amounts of YpeB, GerD, PrkC, GerAC, and GerKC recovered in membrane fractions
      decreased significantly during germination. Lipoproteins, as a protein class,
      decreased during spore germination, while YpeB appeared to be specifically
      degraded. Some protein abundance differences between membrane fractions of
      dormant and superdormant spores resemble protein changes that take place during
      germination, suggesting that the superdormant spore isolation procedure may have
      resulted in early, non-committal germination-associated changes. In addition to
      low levels of germinant receptor proteins, a deficiency in the GerD lipoprotein
      may contribute to heterogeneity of spore germination rates. Understanding the
      reasons for superdormancy may allow for better spore decontamination procedures. 

PMID- 24752280
TI  - A social network approach to the interplay between adolescents' bullying and
      likeability over time.
AB  - Our knowledge on adolescents' bullying behavior has rapidly increased over the
      past decade and it is widely recognized that bullying is a group process and,
      consequently, context-dependent. Only since recently, though, researchers have
      had access to statistical programs to study these group processes appropriately.
      The current 1-year longitudinal study examined the interplay between adolescents'
      bullying and likeability from a social network perspective. Data came from the
      evaluation of the Finnish KiVa antibullying program, consisting of students in
      grades 7-9 (N = 9,183, M age at wave 1 = 13.96 years; 49.2% boys; M classroom
      size = 19.47) from 37 intervention and 30 control schools. Perceived popularity,
      gender, and structural network effects were additionally controlled. Longitudinal
      social network analysis with SIENA revealed that, overall, the higher the
      students' level of bullying, the less they were liked by their peers. Second,
      students liked peers with similar levels of bullying and this selection
      similarity effect was stronger at low levels of bullying. This selection effect
      held after controlling for selection-similarity in perceived popularity and
      gender. Third, students were likely to increase in bullying when they liked peers
      high on bullying and to decrease in bullying when they liked peers low on
      bullying. Again, this influence effect held after controlling for the effects of
      perceived popularity and gender on changes in bullying behavior. No significant
      differences between control and intervention schools appeared in the effects. The
      results are discussed in light of their theoretical and methodological
      implications.

PMID- 24752281
TI  - Day-clinic and inpatient psychotherapy for depression (DIP-D): a randomized
      controlled pilot study in routine clinical care.

PMID- 24752282
TI  - Length tunable penta-twinned palladium nanorods: seedless synthesis and
      electrooxidation of formic acid.
AB  - Palladium nanorods with controlled lengths from 100 to 500 nm and a fixed width
      of 20 nm were synthesized for the first time by a seedless approach. These rods
      show higher peak current densities than Pd cubes for formic acid oxidation and
      the catalytic activity decreases with increasing rod length. 

PMID- 24752283
TI  - Impact of molecular charge on GLUT-specific cellular uptake of glucose bioprobes
      and in vivo application of the glucose bioprobe, GB2-Cy3.
AB  - The molecular charge of fluorescent bioprobes has recently received much
      attention due to its influence on cellular uptake. Herein, we demonstrate the
      effect of the molecular charge of glucose bioprobes on their GLUT-specific
      cellular uptake. We also applied GB2-Cy3 to in vivo imaging in the zebrafish
      model. 

PMID- 24752285
TI  - Extending birthday paradox theory to estimate the number of tags in RFID systems.
AB  - The main objective of Radio Frequency Identification systems is to provide fast
      identification for tagged objects. However, there is always a chance of
      collision, when tags transmit their data to the reader simultaneously. Collision
      is a time-consuming event that reduces the performance of RFID systems.
      Consequently, several anti-collision algorithms have been proposed in the
      literature. Dynamic Framed Slotted ALOHA (DFSA) is one of the most popular of
      these algorithms. DFSA dynamically modifies the frame size based on the number of
      tags. Since the real number of tags is unknown, it needs to be estimated.
      Therefore, an accurate tag estimation method has an important role in increasing
      the efficiency and overall performance of the tag identification process. In this
      paper, we propose a novel estimation technique for DFSA anti-collision algorithms
      that applies birthday paradox theory to estimate the number of tags accurately.
      The analytical discussion and simulation results prove that the proposed method
      increases the accuracy of tag estimation and, consequently, outperforms previous
      schemes. 

PMID- 24752284
TI  - Benefits of phoneme discrimination training in a randomized controlled trial of
      50- to 74-year-olds with mild hearing loss.
AB  - OBJECTIVES: The aims of this study were to (i) evaluate the efficacy of phoneme
      discrimination training for hearing and cognitive abilities of adults aged 50 to
      74 years with mild sensorineural hearing loss who were not users of hearing aids,
      and to (ii) determine participant compliance with a self-administered, computer
      delivered, home- and game-based auditory training program. DESIGN: This study was
      a randomized controlled trial with repeated measures and crossover design.
      Participants were trained and tested over an 8- to 12-week period. One group
      (Immediate Training) trained during weeks 1 and 4. A second waitlist group
      (Delayed Training) did no training during weeks 1 and 4, but then trained during
      weeks 5 and 8. On-task (phoneme discrimination) and transferable outcome measures
      (speech perception, cognition, self-report of hearing disability) for both groups
      were obtained during weeks 0, 4, and 8, and for the Delayed Training group only
      at week 12. RESULTS: Robust phoneme discrimination learning was found for both
      groups, with the largest improvements in threshold shown for those with the
      poorest initial thresholds. Between weeks 1 and 4, the Immediate Training group
      showed moderate, significant improvements on self-report of hearing disability,
      divided attention, and working memory, specifically for conditions or situations
      that were more complex and therefore more challenging. Training did not result in
      consistent improvements in speech perception in noise. There was no evidence of
      any test-retest effects between weeks 1 and 4 for the Delayed Training group.
      Retention of benefit at 4 weeks post-training was shown for phoneme
      discrimination, divided attention, working memory, and self-report of hearing
      disability. Improved divided attention and reduced self-reported hearing
      difficulties were highly correlated. CONCLUSIONS: It was observed that phoneme
      discrimination training benefits some but not all people with mild hearing loss.
      Evidence presented here, together with that of other studies that used different
      training stimuli, suggests that auditory training may facilitate cognitive skills
      that index executive function and the self-perception of hearing difficulty in
      challenging situations. The development of cognitive skills may be more important
      than the development of sensory skills for improving communication and speech
      perception in everyday life. However, improvements were modest. Outcome measures
      need to be appropriately challenging to be sensitive to the effects of the
      relatively small amount of training performed.

PMID- 24752286
TI  - Anti-cancer effect and the underlying mechanisms of gypenosides on human
      colorectal cancer SW-480 cells.
AB  - BACKGROUND: Gypenosides (Gyp), the main components from Gynostemma pentaphyllum
      Makino, are widely used in traditional Chinese medicine. The present study aimed
      to investigate the anti-cancer effect and the underlying mechanisms of Gyp on
      human colorectal cancer cells SW-480. MATERIALS AND METHODS: The inhibitory
      effect of Gyp on SW-480 cells was evaluated by MTT assay. Apoptotic cell death
      was detected by nuclear Hoechst 33342 staining and DNA fragmentation analysis.
      Apoptosis was analyzed using Annexin V-PE/7-amino-actinomycin D staining. Cell
      membrane integrity was evaluated with flow cytometry following PI staining.
      Changes of mitochondrial membrane potential (Deltapsim) were detected through
      flow cytometry analysis of rhodamine 123 (Rh123). The role of reactive oxygen
      species (ROS) in Gyp induced cell death was investigated by intracellular ROS
      generation and general ROS scavenger. Wound-healing assay was carried out to
      investigate Gyp-inhibited migration of SW-480 cells in vitro. Additionally, the
      alterations in F-actin microfilaments were analyzed by FITC-labeled phalloidin
      toxin staining and the morphological changes were evaluated under scanning
      electron microscope (SEM). RESULTS: After the Gyp treatment, the plasma membrane
      permeability of SW-480 cell was increased, Deltapsim was decreased significantly,
      the level of intracellular ROS level was increased, DNA fragmentation and
      apoptotic morphology were observed. Cells treated with Gyp exert serious
      microfilament network collapse as well as the significant decrease in the number
      of microvilli. Gyp induced the changes of cell viability, cell migration,
      intracellular ROS generation and nuclear morphology were alleviated obviously by
      NAC. CONCLUSION: The results in this study implied that ROS play an important
      role in Gyp induced cell toxicity and apoptosis, and the mitochondria damage may
      be upstream of ROS generation post Gyp treatment. The findings of the present
      study provide new evidences for anti-tumor mechanisms by which Gyp induces
      apoptosis in vitro.

PMID- 24752287
TI  - One-hot vector hybrid associative classifier for medical data classification.
AB  - Pattern recognition and classification are two of the key topics in computer
      science. In this paper a novel method for the task of pattern classification is
      presented. The proposed method combines a hybrid associative classifier
      (Clasificador Hibrido Asociativo con Traslacion, CHAT, in Spanish), a coding
      technique for output patterns called one-hot vector and majority voting during
      the classification step. The method is termed as CHAT One-Hot Majority (CHAT
      OHM). The performance of the method is validated by comparing the accuracy of
      CHAT-OHM with other well-known classification algorithms. During the experimental
      phase, the classifier was applied to four datasets related to the medical field.
      The results also show that the proposed method outperforms the original CHAT
      classification accuracy. 

PMID- 24752288
TI  - Translation of the prion protein mRNA is robust in astrocytes but does not
      amplify during reactive astrocytosis in the mouse brain.
AB  - Prion diseases induce neurodegeneration in specific brain areas for undetermined
      reasons. A thorough understanding of the localization of the disease-causing
      molecule, the prion protein (PrP), could inform on this issue but previous
      studies have generated conflicting conclusions. One of the more intriguing
      disagreements is whether PrP is synthesized by astrocytes. We developed a knock
      in reporter mouse line in which the coding sequence of the PrP expressing gene
      (Prnp), was replaced with that for green fluorescent protein (GFP). Native GFP
      fluorescence intensity varied between and within brain regions. GFP was present
      in astrocytes but did not increase during reactive gliosis induced by scrapie
      prion infection. Therefore, reactive gliosis associated with prion diseases does
      not cause an acceleration of local PrP production. In addition to aiding in Prnp
      gene activity studies, this reporter mouse line will likely prove useful for
      analysis of chimeric animals produced by stem cell and tissue transplantation
      experiments. 

PMID- 24752290
TI  - N-alkylated and N,N-dialkylated 1,6-diaminoperylene diimides synthesized via
      copper catalyzed direct aromatic amination.
AB  - Perylene diimides (PDIs) and naphthalene diimides (NDIs) can be efficiently
      aminated with primary or secondary amines under mild conditions using Cu(II)
      salts as catalysts and air as an oxidant. Depending on the substrate and the
      amine, yields over 80% can be obtained by simply stirring the reaction mixture at
      room temperature for one hour.

PMID- 24752291
TI  - The interactions of iota-carrageenan with cationic surfactants in aqueous
      solutions.
AB  - The interactions between the anionic polymer iota-carrageenan (IC) and the
      cationic surfactants 1-dodecyl-3-methylimidazolium bromide (C12mimBr),
      dodecyltrimethylammonium bromide (DTAB) and ethyl-alpha,omega
      bis(dodecyldimethylammonium)dibromide (12-2-12) have been studied by fluorimetry
      and isothermal titration calorimetry. Our experimental results showed that at a
      low surfactant concentration, the monomers adsorbed on the IC chains through the
      electrostatic attraction, followed by the formation of induced micelles on the IC
      chains through the hydrophobic interaction until the IC chains are saturated by
      surfactant molecules; after that the added surfactant formed free micelles in the
      solution. A pseudo-phase-equilibrium thermodynamic model was proposed to explain
      the experimental results and to understand the mechanisms of the interactions in
      these three systems. Moreover, the salt effect on the interactions was
      investigated and found that it changed the critical concentrations but not the
      interaction mechanism. 

PMID- 24752289
TI  - Phase synchronization in electroencephalographic recordings prognosticates
      outcome in paediatric coma.
AB  - Brain injury from trauma, cardiac arrest or stroke is the most important cause of
      death and acquired disability in the paediatric population. Due to the lifetime
      impact of brain injury, there is a need for methods to stratify patient risk and
      ultimately predict outcome. Early prognosis is fundamental to the implementation
      of interventions to improve recovery, but no clinical model as yet exists.
      Healthy physiology is associated with a relative high variability of physiologic
      signals in organ systems. This was first evaluated in heart rate variability
      research. Brain variability can be quantified through electroencephalographic
      (EEG) phase synchrony. We hypothesised that variability in brain signals from EEG
      recordings would correlate with patient outcome after brain injury. Lower
      variability in EEG phase synchronization, would be associated with poor patient
      prognosis. A retrospective study, spanning 10 years (2000-2010) analysed the
      scalp EEGs of children aged 1 month to 17 years in coma (Glasgow Coma Scale, GCS,
      <8) admitted to the paediatric critical care unit (PCCU) following brain injury
      from TBI, cardiac arrest or stroke. Phase synchrony of the EEGs was evaluated
      using the Hilbert transform and the variability of the phase synchrony
      calculated. Outcome was evaluated using the 6 point Paediatric Performance
      Category Score (PCPC) based on chart review at the time of hospital discharge.
      Outcome was dichotomized to good outcome (PCPC score 1 to 3) and poor outcome
      (PCPC score 4 to 6). Children who had a poor outcome following brain injury
      secondary to cardiac arrest, TBI or stroke, had a higher magnitude of synchrony
      (R index), a lower spatial complexity of the synchrony patterns and a lower
      temporal variability of the synchrony index values at 15 Hz when compared to
      those patients with a good outcome. 

PMID- 24752292
TI  - Central motor conduction studies in patients with spinal cord disorders: a
      review.
AB  - STUDY DESIGN: Topical review of the literature. OBJECTIVES: The evaluation of
      patients with myelopathies requires radiological investigations; however, for the
      correct interpretation of the neuroimaging findings, the functional assessment of
      corticospinal conduction is helpful or even mandatory in many conditions. The
      objective of this review article was to assess the utility of the motor evoked
      potentials (MEPs) in diagnosis and management of the most frequent spinal cord
      disorders. SETTING: Salzburg (Austria) and Merano (Italy). METHODS: A MEDLINE
      search was performed using following terms: 'motor evoked potentials',
      'transcranial magnetic stimulation', 'central motor conduction', 'compressive
      myelopathy', 'spinal cord infarction', 'spinal cord injury', 'syringomyelia',
      'myelitis', 'hereditary spastic paraparesis', 'subacute combined degeneration'
      and 'hepatic myelopathy'. RESULTS: Central motor conduction abnormalities can be
      detected also in the absence of neuroradiological abnormalities-for example, in
      patients with subacute combined degeneration or hepatic myelopathy. In the most
      frequent patients with compressive myelopathies, MEPs were found to be very
      helpful in determining the functional significance of neuroimaging findings. MEP
      recording can supplement clinical examination and neuroimaging findings also in
      the assessment of the spinal cord injury level. In patients with spinal cord
      infarction, the MEP study can demonstrate spinal involvement even when
      radiological evidence for spinal cord damage is absent or equivocal, thus
      allowing an important early diagnosis. CONCLUSION: MEPs represent a highly
      sensitive and accurate diagnostic tool in many different spinal cord disorders.
      MEPs can also be useful in follow-up evaluation of motor function during
      treatment and rehabilitation.

PMID- 24752293
TI  - Outcome assessment in conservatively managed patients with cervical spine
      tuberculosis.
AB  - STUDY DESIGN: Cervical spine tuberculosis is a relatively less frequent form of
      spinal tuberculosis. Cervical spine tuberculosis has a greater propensity to
      involve the spinal cord and results in major sensory motor deficit. In this
      prospective study, we aimed to evaluate the clinical and imaging predictors of
      outcome in conservatively managed patients. METHODS: In this study, 42 patients
      of cervical spine tuberculosis were included. Patients were subjected to a
      detailed clinical evaluation and magnetic resonance imaging. Patients were
      treated with antituberculosis treatment and were followed up for 18 months. The
      Modified Barthel index (MBI) was used to assess the disability. Good outcome was
      defined as MBI >12 and poor outcome as MBI ?12. Clinical and imaging
      characteristics were used to analyze the predictors of outcome, using univariate
      and multivariate analysis. RESULTS: Four (9.5%) patients required surgery. Data
      from 38 patients, who were conservatively managed, were analyzed for predictors
      of outcome. Among conservatively managed patients, at presentation, 29 patients
      had an MBI score of ?12. At 18 months, the majority of patients (81.6%) had a
      good outcome. On univariate analysis, a duration of illness >3 months, a major
      motor deficit, bladder involvement, flexor spasms, significant cord compression
      and spinal extension of the abscess were significantly associated with a poor
      outcome. However, on multivariate analysis significant cord compression (P=0.003)
      and spinal extension (P=0.02) showed a significant correlation with a poor
      outcome. CONCLUSION: Medical management was effective in cervical spine
      tuberculosis. Patients with significant cord compression and spinal extension of
      the abscess showed poorer outcome.

PMID- 24752294
TI  - Bioinformatics pipelines for targeted resequencing and whole-exome sequencing of
      human and mouse genomes: a virtual appliance approach for instant deployment.
AB  - Targeted resequencing by massively parallel sequencing has become an effective
      and affordable way to survey small to large portions of the genome for genetic
      variation. Despite the rapid development in open source software for analysis of
      such data, the practical implementation of these tools through construction of
      sequencing analysis pipelines still remains a challenging and laborious activity,
      and a major hurdle for many small research and clinical laboratories. We
      developed TREVA (Targeted REsequencing Virtual Appliance), making pre-built
      pipelines immediately available as a virtual appliance. Based on virtual machine
      technologies, TREVA is a solution for rapid and efficient deployment of complex
      bioinformatics pipelines to laboratories of all sizes, enabling reproducible
      results. The analyses that are supported in TREVA include: somatic and germline
      single-nucleotide and insertion/deletion variant calling, copy number analysis,
      and cohort-based analyses such as pathway and significantly mutated genes
      analyses. TREVA is flexible and easy to use, and can be customised by Linux-based
      extensions if required. TREVA can also be deployed on the cloud (cloud
      computing), enabling instant access without investment overheads for additional
      hardware. TREVA is available at http://bioinformatics.petermac.org/treva/. 

PMID- 24752295
TI  - Type I IFN suppresses Cxcr2 driven neutrophil recruitment into the sensory
      ganglia during viral infection.
AB  - Infection induces the expression of inflammatory chemokines that recruit immune
      cells to the site of inflammation. Whereas tissues such as the intestine and skin
      express unique chemokines during homeostasis, whether different tissues express
      distinct chemokine profiles during inflammation remains unclear. With this in
      mind, we performed a comprehensive screen of the chemokines expressed by two
      tissues (skin and sensory ganglia) infected with a common viral pathogen (herpes
      simplex virus type 1). After infection, the skin and ganglia showed marked
      differences in their expression of the family of Cxcr2 chemokine ligands.
      Specifically, Cxcl1/2/3, which in turn controlled neutrophil recruitment, was up
      regulated in the skin but absent from the ganglia. Within the ganglia, Cxcl2
      expression and subsequent neutrophil recruitment was inhibited by type I
      interferon (IFN). Using a combination of bone marrow chimeras and intracellular
      chemokine staining, we show that type I IFN acted by directly suppressing Cxcl2
      expression by monocytes, abrogating their ability to recruit neutrophils to the
      ganglia. Overall, our findings describe a novel role for IFN in the direct, and
      selective, inhibition of Cxcr2 chemokine ligands, which results in the inhibition
      of neutrophil recruitment to neuronal tissue. 

PMID- 24752296
TI  - Enhancement of an anti-tumor immune response by transient blockade of central T
      cell tolerance.
AB  - Thymic central tolerance is a critical process that prevents autoimmunity but
      also presents a challenge to the generation of anti-tumor immune responses.
      Medullary thymic epithelial cells (mTECs) eliminate self-reactive T cells by
      displaying a diverse repertoire of tissue-specific antigens (TSAs) that are also
      shared by tumors. Therefore, while protecting against autoimmunity, mTECs
      simultaneously limit the generation of tumor-specific effector T cells by
      expressing tumor self-antigens. This ectopic expression of TSAs largely depends
      on autoimmune regulator (Aire), which is expressed in mature mTECs. Thus,
      therapies to deplete Aire-expressing mTECs represent an attractive strategy to
      increase the pool of tumor-specific effector T cells. Recent work has implicated
      the TNF family members RANK and RANK-Ligand (RANKL) in the development of Aire
      expressing mTECs. We show that in vivo RANKL blockade selectively and transiently
      depletes Aire and TSA expression in the thymus to create a window of defective
      negative selection. Furthermore, we demonstrate that RANKL blockade can rescue
      melanoma-specific T cells from thymic deletion and that persistence of these
      tumor-specific effector T cells promoted increased host survival in response to
      tumor challenge. These results indicate that modulating central tolerance through
      RANKL can alter thymic output and potentially provide therapeutic benefit by
      enhancing anti-tumor immunity. 

PMID- 24752297
TI  - Leucine-rich repeat containing 8A (LRRC8A) is essential for T lymphocyte
      development and function.
AB  - Lrrc8a is a ubiquitously expressed gene that encodes a leucine-rich repeat (LRR)
      containing protein detected at higher levels on the surface of thymocytes than on
      other immune cells. We generated Lrrc8a(-/-) mice to investigate the role of
      LRRC8A in lymphocyte development and function. Lrrc8a(-/-) mice had increased
      prenatal and postnatal mortality, growth retardation, and multiple tissue
      abnormalities. Lrrc8a(-/-) mice displayed a modest block in B cell development
      but intact intrinsic B cell function. In contrast, both Lrrc8a(-/-) mice and
      Lrrc8a(-/-)->Rag2(-/-) bone marrow chimeras exhibited a severe cell-intrinsic
      block in early thymic development, with decreased proliferation and increased
      apoptosis of thymocytes, and impaired peripheral T cell function. Thymic
      epithelial cells expressed an LRRC8A ligand that was critical for double-negative
      to double-positive thymocyte differentiation and survival in vitro. LRRC8A
      constitutively associated with the GRB2-GAB2 complex and lymphocyte-specific
      protein tyrosine kinase (LCK) in thymocytes. LRRC8A ligation activated AKT via
      the LCK-ZAP-70-GAB2-PI3K pathway, and AKT phosphorylation was markedly reduced in
      the thymus of Lrrc8a(-/-) mice. These findings reveal an essential role for
      LRRC8A in T cell development, survival, and function. 

PMID- 24752298
TI  - IFN-lambda receptor 1 expression is induced in chronic hepatitis C and correlates
      with the IFN-lambda3 genotype and with nonresponsiveness to IFN-alpha therapies.
AB  - The molecular mechanisms that link IFN-lambda3 genotypes to differential
      induction of interferon (IFN)-stimulated genes (ISGs) in the liver of patients
      with chronic hepatitis C (CHC) are not known. We measured the expression of IFN
      lambda and of the specific IFN-lambda receptor chain (IFN-lambdaR1) in 122 liver
      biopsies of patients with CHC and 53 control samples. The IFN-lambda3 genotype
      was not associated with differential expression of IFN-lambda, but rather IFN
      lambdaR1. In a series of 30 primary human hepatocyte (PHH) samples, IFN-lambdaR1
      expression was low but could be induced with IFN-alpha. IFN-alpha-induced IFN
      lambdaR1 expression was significantly stronger in PHHs carrying the minor IFN
      lambda3 allele. The analysis of liver biopsies of patients with CHC revealed a
      strong association of high IFN-lambdaR1 expression with elevated ISG expression,
      with IFN-lambda3 minor alleles, and with nonresponse to pegylated IFN-alpha and
      ribavirin. The findings provide a missing link between the IFN-lambda3 genotype
      and the associated phenotype of treatment nonresponse. 

PMID- 24752300
TI  - Elucidation of the enigmatic IgD class-switch recombination via germline deletion
      of the IgH 3' regulatory region.
AB  - Classical class-switch recombination (cCSR) substitutes the CMU gene with Cgamma,
      Cepsilon, or Calpha, thereby generating IgG, IgE, or IgA classes, respectively.
      This activation-induced deaminase (AID)-driven process is controlled by the IgH
      3' regulatory region (3'RR). Regulation of rare IgD CSR events has been
      enigmatic. We show that MUdeltaCSR occurs in mouse mesenteric lymph node (MLN) B
      cells and is AID-dependent. AID attacks differ from those in cCSR because they
      are not accompanied by extensive somatic hypermutation (SHM) of targeted regions
      and because repaired junctions exhibit features of the alternative end-joining (A
      EJ) pathway. In contrast to cCSR and SHM, MUdeltaCSR is 3'RR-independent, as its
      absence affects neither breakpoint locations in SMU- and Sdelta-like
      (sigma(delta)) nor mutation patterns at SMU-sigma(delta) junctions. Although
      mutations occur in the immediate proximity of the MUdelta junctions, SHM is
      absent distal to the junctions within both SMU and rearranged VDJ regions. In
      conclusion, MUdeltaCSR is active in MLNs, occurs independently of 3'RR-driven
      assembly, and is even dramatically increased in 3'RR-deficient mice, further
      showing that its regulation differs from cCSR.

PMID- 24752299
TI  - MyD88-dependent interplay between myeloid and endothelial cells in the initiation
      and progression of obesity-associated inflammatory diseases.
AB  - Low-grade systemic inflammation is often associated with metabolic syndrome,
      which plays a critical role in the development of the obesity-associated
      inflammatory diseases, including insulin resistance and atherosclerosis. Here, we
      investigate how Toll-like receptor-MyD88 signaling in myeloid and endothelial
      cells coordinately participates in the initiation and progression of high fat
      diet-induced systemic inflammation and metabolic inflammatory diseases. MyD88
      deficiency in myeloid cells inhibits macrophage recruitment to adipose tissue and
      their switch to an M1-like phenotype. This is accompanied by substantially
      reduced diet-induced systemic inflammation, insulin resistance, and
      atherosclerosis. MyD88 deficiency in endothelial cells results in a moderate
      reduction in diet-induced adipose macrophage infiltration and M1 polarization,
      selective insulin sensitivity in adipose tissue, and amelioration of spontaneous
      atherosclerosis. Both in vivo and ex vivo studies suggest that MyD88-dependent GM
      CSF production from the endothelial cells might play a critical role in the
      initiation of obesity-associated inflammation and development of atherosclerosis
      by priming the monocytes in the adipose and arterial tissues to differentiate
      into M1-like inflammatory macrophages. Collectively, these results implicate a
      critical MyD88-dependent interplay between myeloid and endothelial cells in the
      initiation and progression of obesity-associated inflammatory diseases. 

PMID- 24752301
TI  - RGMb is a novel binding partner for PD-L2 and its engagement with PD-L2 promotes
      respiratory tolerance.
AB  - We report that programmed death ligand 2 (PD-L2), a known ligand of PD-1, also
      binds to repulsive guidance molecule b (RGMb), which was originally identified in
      the nervous system as a co-receptor for bone morphogenetic proteins (BMPs). PD-L2
      and BMP-2/4 bind to distinct sites on RGMb. Normal resting lung interstitial
      macrophages and alveolar epithelial cells express high levels of RGMb mRNA,
      whereas lung dendritic cells express PD-L2. Blockade of the RGMb-PD-L2
      interaction markedly impaired the development of respiratory tolerance by
      interfering with the initial T cell expansion required for respiratory tolerance.
      Experiments with PD-L2-deficient mice showed that PD-L2 expression on non-T cells
      was critical for respiratory tolerance, but expression on T cells was not
      required. Because PD-L2 binds to both PD-1, which inhibits antitumor immunity,
      and to RGMb, which regulates respiratory immunity, targeting the PD-L2 pathway
      has therapeutic potential for asthma, cancer, and other immune-mediated
      disorders. Understanding this pathway may provide insights into how to optimally
      modulate the PD-1 pathway in cancer immunotherapy while minimizing adverse
      events. 

PMID- 24752302
TI  - Improved HSC reconstitution and protection from inflammatory stress and
      chemotherapy in mice lacking granzyme B.
AB  - The serine protease granzyme B (GzmB) is stored in the granules of cytotoxic T
      and NK cells and facilitates immune-mediated destruction of virus-infected cells.
      In this study, we use genetic tools to report novel roles for GzmB as an
      important regulator of hematopoietic stem cell (HSC) function in response to
      stress. HSCs lacking the GzmB gene show improved bone marrow (BM) reconstitution
      associated with increased HSC proliferation and mitochondrial activity. In
      addition, recipients deficient in GzmB support superior engraftment of wild-type
      HSCs compared with hosts with normal BM niches. Stimulation of mice with
      lipopolysaccharide strongly induced GzmB protein expression in HSCs, which was
      mediated by the TLR4-TRIF-p65 NF-kappaB pathway. This is associated with
      increased cell death and GzmB secretion into the BM environment, suggesting an
      extracellular role of GzmB in modulating HSC niches. Moreover, treatment with the
      chemotherapeutic agent 5-fluorouracil (5-FU) also induces GzmB production in
      HSCs. In this situation GzmB is not secreted, but instead causes cell-autonomous
      apoptosis. Accordingly, GzmB-deficient mice are more resistant to serial 5-FU
      treatments. Collectively, these results identify GzmB as a negative regulator of
      HSC function that is induced by stress and chemotherapy in both HSCs and their
      niches. Blockade of GzmB production may help to improve hematopoiesis in various
      situations of BM stress. 

PMID- 24752303
TI  - Sleep disorders in combat-related PTSD.
AB  - PURPOSE: We sought to assess the rate of sleep complaints and sleep disorders
      among active duty soldiers with deployment-related PTSD and to determine whether
      any clinical features differentiated those with sleep disorders. METHODS:
      Retrospective review of consecutive soldiers diagnosed with PTSD. We recorded
      subjective measures of sleep and polysomnographic data. We compared clinical and
      demographic variables including psychoactive medication use, psychiatric
      comorbidity, and combat-related traumatic injury with the presence of sleep
      disorders. RESULTS: One hundred thirty patients were included (91.5 % male, mean
      age of 35.1 +/- 10.6 years, mean body mass index (BMI) 28.9 +/- 4.4 Kg/m(2)).
      About 88.5 % had comorbid depression, with the majority (96.2 %) taking
      psychoactive medications (mean 3.4 +/- 1.6 medications per patient). Over half of
      the cohort suffered combat-related traumatic physical injuries (54.6 %). The
      obstructive sleep apnea syndrome (OSAS) was diagnosed in 67.3 % (80 % of the
      cohort underwent polysomnography), with a mean apnea hypopnea index of 24.1 +/-
      22.8 events/hour and a mean oxygen saturation nadir of 84.2 +/- 5.7 %. OSAS was
      significantly more common in the non-injured soldiers (72.9 vs. 38.0 %, p <
      0.001). In multivariate analysis, absence of physical injury showed a trend
      towards predicting OSAS. CONCLUSIONS: Sleep complaints are common among soldiers
      with PTSD. We observed significantly higher rates of OSAS among those without
      physical injuries, raising the possibility that underlying sleep-disordered
      breathing is a risk factor for the development of PTSD. This potential
      association requires further validation.

PMID- 24752304
TI  - oxLDL-induced lipid accumulation in glomerular podocytes: role of IFN-gamma,
      CXCL16, and ADAM10.
AB  - Previous studies have shown that lipid accumulation plays an important role in
      the pathogenesis and development of glomerular sclerosis. oxLDL caused damage in
      renal mesangial cells, endothelial cells, and podocytes, and podocytes might be
      the major victim of oxLDL insult. However, the regulatory mechanism of how oxLDL
      induces the damage of podocytes remains to be elucidated. In this study, oil red
      staining was used to investigate the lipid accumulation in podocytes. Moreover,
      the effects of CXCL16 antibody, IFN-gamma, and ADAM10 inhibitor on oxLDL intake
      and CXCL16 expression were also explored to elucidate the regulatory factors of
      lipid accumulation in podocytes. 

PMID- 24752305
TI  - Free flap combined with external fixator in the treatment of open fractures of
      the calf.
AB  - The objective of this study was to investigate the clinical effect of the
      treatment of open fractures of the leg using free flap in combination with
      external fixation, in order to improve the therapeutic outcomes. A retrospective
      analysis including 70 cases of leg open fracture patients between May 2010 and
      February 2013 was conducted. The patients were categorized into two groups: the
      control group of 35 patients, treated with the use of external fixation; and the
      observational group of 35 patients in the control group treated on the basis of
      the addition of free flap. Clinical effects were compared between the two groups
      after treatment. From the viewpoint of clinical effects, the number of cases in
      the control group with excellent, good, fair, and poor outcomes were found to be
      6, 13, 11, and 5, respectively, and the respective ratios were 17.14, 37.14,
      31.43, and 14.29 %; the number of cases in the observational group with
      excellent, good, fair, and poor outcomes were 15, 10, 8, and 2, respectively,
      with the respective ratios being 42.86, 28.57, 22.86, and 5.71 %, respectively;
      there were significant differences (p < 0.05); two groups in the use of
      antibiotics in the number of days, number of dressing changes, debridement to
      terminal operation time, the number of operations, length of stay, time of pain
      had more significant differences (p < 0.05); term complication of the control
      group was 45.71 %, and the long-term complication rate was 54.29 %; in the
      observational group, recent complication rate was 17.14 %, and the long-term
      complication was 20 %--with the two groups being significantly different (p <
      0.05), and the above being statistically significant. The long-term effect for
      the group treated with the free flap in combination with external fixation for
      leg open fractures is good.

PMID- 24752307
TI  - The inconclusive results of the studies on glycoprotein IIIa platelet receptor
      gene polymorphism and coronary artery disease: an area of darkness.

PMID- 24752309
TI  - Design of tetraplex specific ligands: cyclic naphthalene diimide.
AB  - Cyclic naphthalene diimide 1 bound to hybrid-type tetraplex DNA from 5'
      AGGG(TTAGGG)3-3' (K = 8.6 * 10(6) M(-1)) with 260-fold greater affinity than
      binding to a double stranded oligonucleotide consisting of 5'-GGG AGG TTT CGC-3'
      and 3'-CCC TCC AAA GCG-5' (nK = 3.3 * 10(4) M(-1)) with 0.5 MUM of IC50 for
      telomerase activity. 

PMID- 24752308
TI  - How common are long-lasting, intensely itching vaccination granulomas and contact
      allergy to aluminium induced by currently used pediatric vaccines? A prospective
      cohort study.
AB  - The frequency of long-lasting, intensely itching subcutaneous nodules at the
      injection site for aluminium (Al)-adsorbed vaccines (vaccination granulomas) was
      investigated in a prospective cohort study comprising 4,758 children who received
      either a diphtheria-tetanus-pertussis-polio-Haemophilus influenzae type b vaccine
      (Infanrix(r), Pentavac(r)) alone or concomitant with a pneumococcal conjugate
      (Prevenar). Both vaccines were adsorbed to an Al adjuvant. Altogether 38 children
      (0.83 %) with itching granulomas were identified, epicutaneously tested for Al
      sensitisation and followed yearly. Contact allergy to Al was verified in 85 %.
      The median duration of symptoms was 22 months in those hitherto recovered. The
      frequency of granulomas induced by Infanrix(r) was >0.66 % and by Prevenar >0.35
      %. The risk for granulomas increased from 0.63 to 1.18 % when a second Al
      adsorbed vaccine was added to the schedule. CONCLUSION: Long-lasting itching
      vaccination granulomas are poorly understood but more frequent than previously
      known after infant vaccination with commonly used diphtheria-tetanus-pertussis
      polio-Haemophilus influenzae type b and pneumococcal conjugate vaccines. The risk
      increases with the number of vaccines given. Most children with itching
      granulomas become contact allergic to aluminium. Itching vaccination granulomas
      are benign but may be troublesome and should be recognised early in primary
      health care to avoid unnecessary investigations, anxiety and mistrust.

PMID- 24752310
TI  - Ancestry-based pharmacogenomics, adverse reactions and carbamazepine: is the FDA
      warning correct?
AB  - In an effort to prevent potentially fatal adverse reactions to carbamazepine, the
      US Food and Drug Administration (FDA) issued an alert in 2007 containing
      pharmacogenomic information, which is still in effect today. The alert states
      that carbamazepine-induced skin reactions are significantly more common in
      patients with the human leukocyte antigen (HLA)-B*1502 allele and that these
      people are almost exclusively from 'broad areas of Asia, including South Asian
      Indians.' This study reviews the medical evidence relied upon by the FDA and
      finds that the alert does not accurately reflect the medical evidence relied upon
      in 2007 or evidence that has been generated over the last 5 years since the label
      was created. The FDA drug labeling should be modified to reflect current medical
      evidence. 

PMID- 24752311
TI  - Association of PAX4 genetic variants with oral antidiabetic drugs efficacy in
      Chinese type 2 diabetes patients.
AB  - The aim of this study was to investigate the association of PAX4 variants with
      therapeutic effect of oral antidiabetic drugs in Chinese type 2 diabtes mellitus
      (T2DM) patients. A total of 209 newly diagnosed T2DM patients were randomly
      assigned to treatment with repaglinide or rosiglitazone for 48 weeks, and the
      therapeutic effects were compared. In the rosiglitazone cohort, rs6467136 GA+AA
      carriers showed greater decrease in 2-h glucose levels (P=0.0063) and higher
      cumulative attainment rates of target 2-h glucose levels (Plog rank=0.0093) than
      GG homozygotes. In the subgroup with defective beta-cell function, rs6467136
      GA+AA carriers exhibited greater decrements of 2-h glucose level and improvement
      of homeostasis model assessment of insulin resistance (P=0.0143). Moreover, GA+AA
      carriers were more likely to attain the target fasting and 2-h glucose level
      (Plog rank=0.0091 and 0.007, respectively). However, these single-nucleotide
      polymorphisms showed no effect on repaglinide efficacy. In conclusion, PAX4
      variant rs6467136 was associated with the therapeutic effect of rosiglitazone in
      Chinese T2DM patients. 

PMID- 24752312
TI  - Enhancing adult nerve regeneration through the knockdown of retinoblastoma
      protein.
AB  - Tumour suppressor pathways may offer novel targets capable of altering the
      plasticity of post-mitotic adult neurons. Here we describe a role for the
      retinoblastoma (Rb) protein, widely expressed in adult sensory neurons and their
      axons, during regeneration. In adult sensory neurons, Rb short interfering RNA
      (siRNA) knockdown or Rb1 deletion in vitro enhances neurite outgrowth and
      branching. Plasticity is achieved in part through upregulation of neuronal
      PPARupsilon; its antagonism inhibits Rb siRNA plasticity, whereas a PPARupsilon
      agonist increases growth. In an in vivo regenerative paradigm following complete
      peripheral nerve trunk transection, direct delivery of Rb siRNA prompts increased
      outgrowth of axons from proximal stumps and entrains Schwann cells to accompany
      them for greater distances. Similarly, Rb siRNA delivery following a nerve crush
      improves behavioural indices of motor and sensory recovery in mice. The overall
      findings indicate that inhibition of tumour suppressor molecules has a role to
      play in promoting adult neuron regeneration. 

PMID- 24752313
TI  - Dietary habits and supplement use in relation to national pregnancy
      recommendations: data from the EuroPrevall birth cohort.
AB  - Assessing maternal dietary habits across Europe during pregnancy in relation to
      their national pregnancy recommendations. A collaborative, multi-centre, birth
      cohort study in nine European countries was conducted as part of European Union
      funded EuroPrevall project. Standardised baseline questionnaire data included
      details of food intake, nutritional supplement use, exposure to cigarette smoke
      during pregnancy and socio-demographic data. Pregnancy recommendations were
      collected from all nine countries from the appropriate national organisations.
      The most commonly taken supplement in pregnancy was folic acid (55.6 % Lithuania
      97.8 % Spain) and was favoured by older, well-educated mothers. Vitamin D
      supplementation across the cohort was very poor (0.3 % Spain-5.1 % Lithuania).
      There were significant differences in foods consumed in different countries
      during pregnancy e.g. only 2.7 % Dutch mothers avoided eating peanut, while 44.4
      % of British mothers avoided it. Some countries have minimal pregnancy
      recommendations i.e. Lithuania, Poland and Spain while others have similar, very
      specific recommendations i.e. UK, the Netherlands, Iceland, Greece. Allergy
      specific recommendations were associated with food avoidance during pregnancy
      [relative rate (RR) 1.18 95 % CI 0.02-1.37]. Nutritional supplement
      recommendations were also associated with avoidance (RR 1.08, 1.00-1.16).
      Maternal dietary habits and the use of dietary supplements during pregnancy vary
      significantly across Europe and in some instances may be influenced by national
      recommendations.

PMID- 24752314
TI  - Intendedness of pregnancy and other predictive factors for symptoms of prenatal
      depression in a population-based study.
AB  - Prenatal depression (PD) as a risk factor for adverse birth outcomes is well
      documented. Less is known about maternal risks for PD, which could inform
      preventive strategies for perinatal and interconceptional care. This exploratory
      study investigates associations between prenatal depression symptoms and
      unintended and mistimed pregnancies and other maternal risk factors for PD. A
      subset of birth records from the New York Statewide Perinatal Data System (n =
      19,219) was used in this secondary analysis of cross-sectional data. Univariate
      and multivariate multinomial regression was used to identify factors that are
      independently associated with four self-reported levels of prenatal depression
      symptoms. Women with unintended pregnancies were more likely (AOR, 95 % CI) to
      report severe (3.6, 2.6-5.1) or moderate (2.0, 1.6-2.5) prenatal depression
      symptoms and less likely to report no symptoms, compared to women with intended
      pregnancies. Likewise, women with mistimed pregnancies were more likely to report
      severe (2.7, 2.2-3.5) or moderate (1.7, 1.5-2.1) prenatal depression symptoms
      than no symptoms, compared to women with intended pregnancies. Low education,
      drug use, smoking, minority race, being unmarried and having Medicaid insurance
      were also significant, independent predictors of PD symptoms. Results suggest
      that routine screening for depression, intendedness of pregnancy and other
      associated risk factors such as smoking and drug use during prenatal and
      interconceptional care visits may enable coordinated interventions that can
      reduce prenatal depression and unintended and mistimed pregnancies and improve
      pregnancy outcomes.

PMID- 24752315
TI  - Maternal knowledge, attitudes and self-efficacy in relation to intention to
      exclusively breastfeed among pregnant women in rural Bangladesh.
AB  - Achieving optimal exclusive breastfeeding (EBF) remains a challenge. Because
      intention is a precursor of practice, we examined factors associated with EBF
      intention during pregnancy in two rural sub-districts of Kishoreganj district,
      Bangladesh. We studied 2,400 pregnant women in their third trimester (26-32 weeks
      gestation). We assessed knowledge (6 items, scale range 0-6), attitudes (15
      items, scale range 15-75) and self-efficacy (6 items, scale range 6-30) by
      interview using a standardized questionnaire. 83.9 % of pregnant women reported
      EBF intention. Mean breastfeeding knowledge was 3.5 (SD 1.3), mean attitude was
      55.8 (SD 8.1) and mean self-efficacy was 25.6 (SD 3.4). Knowledge was associated
      with EBF intention (OR 2.47, 95 % CI 1.74, 3.51), attitudes toward EBF (OR 1.68,
      95 % CI 1.31, 2.16) and self-efficacy (OR 1.72, 95 % CI 1.23, 2.40) were
      independently associated with EBF intention in the model in which all three
      constructs were entered simultaneously. Receipt of breastfeeding counseling
      during pregnancy and being literate were each associated with EBF knowledge and
      EBF intention (all p < 0.05). Increasing maternal knowledge, positive attitudes,
      and self-efficacy regarding EBF were associated with prenatal EBF intention.
      These results reinforce the importance of appropriate counseling to increase EBF
      prevalence .

PMID- 24752316
TI  - Extending the sRNAome of apple by next-generation sequencing.
AB  - The global importance of apple as a fruit crop necessitates investigations into
      molecular aspects of the processes that influence fruit quality and yield,
      including plant development, fruit ripening and disease resistance. In order to
      study and understand biological processes it is essential to recognise the range
      of molecules, which influence these processes. Small non-coding RNAs are
      regulatory agents involved in diverse plant activities, ranging from development
      to stress response. The occurrence of these molecules in apple leaves was studied
      by means of next-generation sequencing. 85 novel microRNA (miRNA) gene loci were
      predicted and characterized along with known miRNA loci. Both cis- and trans
      natural antisense transcript pairs were identified. Although the trans
      overlapping regions were enriched in small RNA (sRNA) production, cis-overlaps
      did not seem to agree. More than 150 phased regions were also identified, and for
      a small subset of these, potential miRNAs that could initiate phasing, were
      revealed. Repeat-associated siRNAs, which are generated from repetitive genomic
      regions such as transposons, were also analysed. For this group almost all
      available repeat sequences, associated with the apple genome and present in
      Repbase, were found to produce siRNAs. Results from this study extend our current
      knowledge on apple sRNAs and their precursors significantly. A rich molecular
      resource has been created and is available to the research community to serve as
      a baseline for future studies. 

PMID- 24752317
TI  - The differentiation of human adipose-derived stem cells towards a urothelium-like
      phenotype in vitro and the dynamic temporal changes of related cytokines by both
      paracrine and autocrine signal regulation.
AB  - PURPOSE: To investigate the differentiation ability of human adipose-derived stem
      cells (ASCs) towards urothelium-like cells in vitro and the dynamic changes of
      related cytokines and cytokine receptors in the culture medium. MATERIALS AND
      METHODS: The ASCs were induced using both conditioned media (CM) and the
      transwell co-culture system with an immortalized urothelium cell line (SV-HUC
      1,HUC) for 21 days. Protein and mRNA expression of the mature urothelium specific
      markers uroplakin-IA (UP-1A) and uroplakin-II (UP-II) were detected by
      immunofluorescence and quantitative real-time PCR, respectively. Array detection
      was used to screen 41 cytokines and receptors in the upper medium of urothelium,
      non-induced ASCs and urothelium-induced ASCs at three time points, early (12
      hours), intermediate (7 days) and late (21 days). RESULTS: After induction for 7
      days, the ASCs grown in both CM and transwell co-culture system expressed
      uroplakin-IA (13.54+/-2.00%; 17.28+/-1.84%) and uroplakin-II (19.49+/-1.73%;
      13.98+/-1.47%). After induction for 21 days, ASCs grown in co-culture had
      significantly increased expression of uroplakin-IA (48.03+/-1.25%; 49.57+/-2.85%)
      and uroplakin-II (45.38+/-2.50%; 46.58+/-1.95%). In the upper medium of
      urothelium, 28 cytokines and 8 cytokine receptors had significantly higher
      expression than the counterpart of non-induced ASCs. After 7 days induction, the
      expression of 22 cytokines and 8 cytokine receptors was significantly elevated in
      the upper medium of induced ASCs compared to non-induced ASCs. At the early and
      intermediate time points, ASCs secreted high levels of relative cytokines and
      soluble receptors, but their expressions decreased significantly at the late time
      point. CONCLUSION: The adipose-derived stem cells have the potential to be
      differentiated into urothelium-like cells in vitro by both CM and transwell co
      culture system with mature urothelium. Numerous cytokines and receptors were
      involved in the differentiation process with dynamic temporal changes by both
      paracrine and autocrine signal regulation. Further studies should be carried out
      to determine the detailed mechanism of cytokines and receptors and to enhance the
      urothelium differentiation efficiency of ASCs.

PMID- 24752318
TI  - Fibronectin matrix polymerization regulates smooth muscle cell phenotype through
      a Rac1 dependent mechanism.
AB  - Smooth muscle cells are maintained in a differentiated state in the vessel wall,
      but can be modulated to a synthetic phenotype following injury. Smooth muscle
      phenotypic modulation is thought to play an important role in the pathology of
      vascular occlusive diseases. Phenotypically modulated smooth muscle cells exhibit
      increased proliferative and migratory properties that accompany the
      downregulation of smooth muscle cell marker proteins. Extracellular matrix
      proteins, including fibronectin, can regulate the smooth muscle phenotype when
      used as adhesive substrates. However, cells produce and organize a 3-dimensional
      fibrillar extracellular matrix, which can affect cell behavior in distinct ways
      from the protomeric 2-dimensional matrix proteins that are used as adhesive
      substrates. We previously showed that the deposition/polymerization of
      fibronectin into the extracellular matrix can regulate the deposition and
      organization of other extracellular matrix molecules in vitro. Further, our
      published data show that the presence of a fibronectin polymerization inhibitor
      results in increased expression of smooth muscle cell differentiation proteins
      and inhibits vascular remodeling in vivo. In this manuscript, we used an in vitro
      cell culture system to determine the mechanism by which fibronectin
      polymerization affects smooth muscle phenotypic modulation. Our data show that
      fibronectin polymerization decreases the mRNA levels of multiple smooth muscle
      differentiation genes, and downregulates the levels of smooth muscle alpha-actin
      and calponin proteins by a Rac1-dependent mechanism. The expression of smooth
      muscle genes is transcriptionally regulated by fibronectin polymerization, as
      evidenced by the increased activity of luciferase reporter constructs in the
      presence of a fibronectin polymerization inhibitor. Fibronectin polymerization
      also promotes smooth muscle cell growth, and decreases the levels of actin stress
      fibers. These data define a Rac1-dependent pathway wherein fibronectin
      polymerization promotes the SMC synthetic phenotype by modulating the expression
      of smooth muscle cell differentiation proteins. 

PMID- 24752319
TI  - TAT-protein blockade during ischemia/reperfusion reveals critical role for p85
      PI3K-PTEN interaction in cardiomyocyte injury.
AB  - Recent work shows that cooling protection after mouse cardiac arrest and
      cardiomyocyte ischemia is mediated by Akt activation. The PI3K p85 subunit can
      either augment or inhibit Akt activation depending on its binding to p110 or PTEN
      respectively. To further clarify the role of PI3K p85 in cardioprotection, we
      studied novel TAT-p85 fusion proteins that selectively inhibit PI3K p85 binding.
      We hypothesized that TAT fused p85 lacking the PTEN binding site (TAT-DeltaPTEN
      p85) would enhance Akt phosphorylation to afford cardioprotection. Conversely,
      TAT fused p85 lacking the p110 binding site (TAT-Deltap110p85) would decrease Akt
      phosphorylation and abrogate cardioprotection. Microscopy and Western blot
      analysis demonstrated that TAT fusion protein was transduced into cardiomyocytes
      within 5 min and remained more than 2 h. Inhibition of PI3K/Akt by TAT-Deltap110
      p85 significantly increased cell death from 44.6+/-2.7% to 92.5+/-3.4% after
      simulated ischemia and reperfusion. By contrast, PTEN inhibition using TAT
      DeltaPTEN p85 decreased cell death to 11.9+/-5.3%, a similar level of
      cardioprotection seen with past cooling studies. Additional studies with the
      small molecule PTEN inhibitor VO-OHpic confirmed that PTEN inhibition was highly
      protective against cell death induced by ischemia and reperfusion. We conclude
      that blockade of p85-PTEN interaction and PTEN inhibition may be promising
      strategies for rescuing the heart from ischemia and reperfusion injury. 

PMID- 24752320
TI  - Formation of a polarised primitive endoderm layer in embryoid bodies requires
      fgfr/erk signalling.
AB  - The primitive endoderm arises from the inner cell mass during mammalian pre
      implantation development. It faces the blastocoel cavity and later gives rise to
      the extraembryonic parietal and visceral endoderm. Here, we investigate a key
      step in primitive endoderm development, the acquisition of apico-basolateral
      polarity and epithelial characteristics by the non-epithelial inner cell mass
      cells. Embryoid bodies, formed from mouse embryonic stem cells, were used as a
      model to study this transition. The outer cells of these embryoid bodies were
      found to gradually acquire the hallmarks of polarised epithelial cells and
      express markers of primitive endoderm cell fate. Fgf receptor/Erk signalling is
      known to be required for specification of the primitive endoderm, but its role in
      polarisation of this tissue is less well understood. To investigate the function
      of this pathway in the primitive endoderm, embryoid bodies were cultured in the
      presence of a small molecule inhibitor of Mek. This inhibitor caused a loss of
      expression of markers of primitive endoderm cell fate and maintenance of the
      pluripotency marker Nanog. In addition, a mislocalisation of apico-basolateral
      markers and disruption of the epithelial barrier, which normally blocks free
      diffusion across the epithelial cell layer, occurred. Two inhibitors of the Fgf
      receptor elicited similar phenotypes, suggesting that Fgf receptor signalling
      promotes Erk-mediated polarisation. This data shows that primitive endoderm cells
      of the outer layer of embryoid bodies gradually polarise, and formation of a
      polarised primitive endoderm layer requires the Fgf receptor/Erk signalling
      pathway. 

PMID- 24752321
TI  - Trypanosoma cruzi infection down-modulates the immunoproteasome biosynthesis and
      the MHC class I cell surface expression in HeLa cells.
AB  - Generally, Trypanosoma cruzi infection in human is persistent and tends to
      chronicity, suggesting that the parasite evade the immune surveillance by down
      regulating the intracellular antigen processing routes. Within the MHC class I
      pathway, the majority of antigenic peptides are generated by the proteasome.
      However, upon IFN-gamma stimulation, the catalytic constitutive subunits of the
      proteasome are replaced by the subunits beta1i/LMP2, beta2i/MECL-1 and
      beta5i/LMP7 to form the immunoproteasome. In this scenario, we analyzed whether
      the expression and activity of the constitutive and the immunoproteasome as well
      as the expression of other components of the MHC class I pathway are altered
      during the infection of HeLa cells with T. cruzi. By RT-PCR and two-dimensional
      gel electrophoresis analysis, we showed that the expression and composition of
      the constitutive proteasome is not affected by the parasite. In contrast, the
      biosynthesis of the beta1i, beta2i, beta5i immunosubunits, PA28beta, TAP1 and the
      MHC class I molecule as well as the proteasomal proteolytic activities were down
      regulated in infected-IFN-gamma-treated cell cultures. Taken together, our
      results provide evidence that the protozoan T. cruzi specifically modulates its
      infection through an unknown posttranscriptional mechanism that inhibits the
      expression of the MHC class I pathway components. 

PMID- 24752322
TI  - Influence of polyvinyl chloride infusion extension tube on propofol injection
      pain: a randomised controlled study.
AB  - BACKGROUND: Propofol injection pain is a common and unsolved anaesthesia problem.
      OBJECTIVES: The present study attempted to confirm that the plasticiser di(2
      ethylhexyl) phthalate in polyvinyl chloride (PVC) infusion tubes may increase
      propofol injection pain by increasing the aqueous propofol concentration. DESIGN:
      A randomised controlled study. SETTING: University teaching hospital, 1 April to
      25 June 2013. PATIENTS: One hundred patients scheduled for elective surgery were
      allocated randomly to the PVC or the control (C) group. The PVC group received a
      propofol (Diprivan) infusion via a 1-m PVC infusion extension tube, whereas group
      C received propofol injected directly through the port of the cannula.
      INTERVENTION: After the syringe was loaded with propofol, air was expelled from
      the tube and the syringe was left standing for 5 min; intravenous propofol 0.5 mg
      kg was then injected either through the PVC tube or directly into the cannula.
      MAIN OUTCOME MEASURE: A verbal rating scale was used to evaluate the propofol
      injection pain in both groups. Di(2-ethylhexyl) phthalate and aqueous propofol
      concentrations were also measured in samples of propofol after simulated
      injection. To investigate whether the increase in aqueous propofol concentration
      was caused by leached di(2-ethylhexyl) phthalate, the same amount of di(2
      ethylhexyl) phthalate as that measured in the PVC group was added to the samples
      (group D). RESULTS: The incidences of pain in groups PVC and C were 88 and 46%,
      respectively (P < 0.0001). The di(2-ethylhexyl) phthalate concentration in group
      PVC (1.01 +/- 0.07 MUg ml) was greater than that in group C (lower than the
      detection limit of 0.03 MUg ml). No significant difference was found between the
      aqueous propofol concentrations in groups PVC (25.9 +/- 1.8 MUg ml) and D (24.4
      +/- 1.1 MUg ml) (P = 0.22), which were significantly higher than that in group C
      (14.3 +/- 1.0 MUg ml) (P = 0.079). CONCLUSION: Propofol injection pain is
      increased by contact with PVC infusion tubing as a result of an increase in
      aqueous propofol concentration caused by di(2-ethylhexyl) phthalate leaching into
      the lipid emulsion. TRIAL REGISTRATION: chictr.org identifier: ChiCTR-TRC
      12003170.

PMID- 24752323
TI  - The impact of body mass index on short- and long-term outcomes in patients
      undergoing coronary artery graft bypass.
AB  - OBJECTIVE: This study was designed to investigate the impact of body mass index
      (BMI) on short- and long-term outcomes after initial revascularization with
      coronary artery bypass graft (CABG) surgery. METHODS: 4916 Chinese who
      consecutively underwent isolated, primary CABG at the Cardiovascular Institute of
      Fuwai Hospital from January 1, 1999 to December 31, 2005 were included in this
      study. They were classified based on BMI as follows: underweight: <18.5 kg/m2,
      normal weight: 18.5 to 23.9 kg/m2, overweight: 24 to 27.9 kg/m2, obesity: 28 to
      32 kg/m2, and severe obesity: >32 kg/m2. Short (in-hospital) and long-term (5
      years) major post-operative complications and mortalities were compared among
      various BMI groups after initial revascularization. RESULTS: Multiple regression
      analysis of five years follow-up of clinical end points indicated that various
      BMI groups were not associated with significant differences in 5 years mortality
      and MACCE, however, old age, smoking, hypertension, myocardial infarction and
      heart failure were the risk factor for the mortality. CONCLUSIONS: In this large
      scale study with long term follow-up after primary CABG in an exclusively ethnic
      Chinese population, we found that different BMI groups were not significantly
      associated with 5-years mortality and MACCE, however, old age, smoking,
      hypertension, myocardial infarction and heart failure were the risk factors of
      post-operative mortality, and old age, hypertension and heart failure increased
      the rate of MACCE.

PMID- 24752324
TI  - The role of indoleamine 2,3 dioxygenase in beneficial effects of stem cells in
      hind limb ischemia reperfusion injury.
AB  - Ischemia-Reperfusion (IR) injury of limb remains a significant clinical problem
      causing secondary complications and restricting clinical recovery, despite rapid
      restoration of blood flow and successful surgery. In an attempt to further
      improve post ischemic tissue repair, we investigated the effect of a local
      administration of bone marrow derived stem cells (BMDSCs) in the presence or
      absence of immune-regulatory enzyme, IDO, in a murine model. A whole limb warm
      ischemia-reperfusion model was developed using IDO sufficient (WT) and deficient
      (KO) mice with C57/BL6 background. Twenty-four hours after injury, 5 * 105 cells
      (5*105 cells/200 uL of PBS solution) BMDSCs (Sca1 + cells) were injected
      intramuscularly while the control group received just the vehicle buffer (PBS).
      Forty-eight to seventy-two hours after limb BMDSC injection, recovery status
      including the ratio of intrinsic paw function between affected and normal paws,
      general mobility, and inflammatory responses were measured using video
      micrometery, flow cytometry, and immunohistochemistry techniques. Additionally,
      MRI/MRA studies were performed to further study the inflammatory response between
      groups and to confirm reconstitution of blood flow after ischemia. For the first
      time, our data, showed that IDO may potentially represent a partial role in
      triggering the beneficial effects of BMDSCs in faster recovery and protection
      against structural changes and cellular damage in a hind limb IR injury setting
      (P = 0.00058).

PMID- 24752325
TI  - Granulopoiesis requires increased C/EBPalpha compared to monopoiesis, correlated
      with elevated Cebpa in immature G-CSF receptor versus M-CSF receptor expressing
      cells.
AB  - C/EBPalpha is required for the formation of granulocyte-monocyte progenitors;
      however, its role in subsequent myeloid lineage specification remains uncertain.
      Transduction of murine marrow with either of two Cebpa shRNAs markedly increases
      monocyte and reduces granulocyte colonies in methylcellulose or the monocyte to
      neutrophil ratio in liquid culture. Similar findings were found after marrow
      shRNA transduction and transplantation and with CEBPA knockdown in human marrow
      CD34+ cells. These results apparently reflect altered myeloid lineage
      specification, as similar knockdown allowed nearly complete 32Dcl3 granulocytic
      maturation. Cebpa knockdown also generated lineage-negative blasts with increased
      colony replating capacity but unchanged cell cycle parameters, likely reflecting
      complete differentiation block. The shRNA having the greatest effect on lineage
      skewing reduced Cebpa 3-fold in differentiating cells but 6-fold in accumulating
      blasts. Indicating that Cebpa is the relevant shRNA target, shRNA-resistant
      C/EBPalpha-ER rescued marrow myelopoiesis. Cebpa knockdown in murine marrow cells
      also increased in vitro erythropoiesis, perhaps reflecting 1.6-fold reduction in
      PU.1 leading to GATA-1 derepression. Global gene expression analysis of lineage
      negative blasts that accumulate after Cebpa knockdown demonstrated reduction in
      Cebpe and Gfi1, known transcriptional regulators of granulopoiesis, and also
      reduced Ets1 and Klf5. Populations enriched for immature granulocyte or monocyte
      progenitor/precursors were isolated by sorting Lin-Sca-1-c-Kit+ cells into
      GCSFR+MCSFR- or GCSFR-MCSFR+ subsets. Cebpa, Cebpe, Gfi1, Ets1, and Klf5 RNAs
      were increased in the c-Kit+GCSFR+ and Klf4 and Irf8 in the c-Kit+MCSFR+
      populations, with PU.1 levels similar in both. In summary, higher levels of
      C/EBPalpha are required for granulocyte and lower levels for monocyte lineage
      specification, and this myeloid bifurcation may be facilitated by increased Cebpa
      gene expression in granulocyte compared with monocyte progenitors. 

PMID- 24752326
TI  - Acute exercise leads to regulation of telomere-associated genes and microRNA
      expression in immune cells.
AB  - Telomeres are specialized nucleoprotein structures that protect chromosomal ends
      from degradation. These structures progressively shorten during cellular division
      and can signal replicative senescence below a critical length. Telomere length is
      predominantly maintained by the enzyme telomerase. Significant decreases in
      telomere length and telomerase activity are associated with a host of chronic
      diseases; conversely their maintenance underpins the optimal function of the
      adaptive immune system. Habitual physical activity is associated with longer
      leukocyte telomere length; however, the precise mechanisms are unclear. Potential
      hypotheses include regulation of telomeric gene transcription and/or microRNAs
      (miRNAs). We investigated the acute exercise-induced response of telomeric genes
      and miRNAs in twenty-two healthy males (mean age = 24.1+/-1.55 years).
      Participants undertook 30 minutes of treadmill running at 80% of peak oxygen
      uptake. Blood samples were taken before exercise, immediately post-exercise and
      60 minutes post-exercise. Total RNA from white blood cells was submitted to miRNA
      arrays and telomere extension mRNA array. Results were individually validated in
      white blood cells and sorted T cell lymphocyte subsets using quantitative real
      time PCR (qPCR). Telomerase reverse transcriptase (TERT) mRNA (P = 0.001) and
      sirtuin-6 (SIRT6) (P<0.05) mRNA expression were upregulated in white blood cells
      after exercise. Fifty-six miRNAs were also differentially regulated post-exercise
      (FDR <0.05). In silico analysis identified four miRNAs (miR-186, miR-181, miR-15a
      and miR-96) that potentially targeted telomeric gene mRNA. The four miRNAs
      exhibited significant upregulation 60 minutes post-exercise (P<0.001). Telomeric
      repeat binding factor 2, interacting protein (TERF2IP) was identified as a
      potential binding target for miR-186 and miR-96 and demonstrated concomitant
      downregulation (P<0.01) at the corresponding time point. Intense
      cardiorespiratory exercise was sufficient to differentially regulate key
      telomeric genes and miRNAs in white blood cells. These results may provide a
      mechanistic insight into telomere homeostasis and improved immune function and
      physical health. 

PMID- 24752327
TI  - Correlation of LMP10 expression and clinical outcome in Human Papillomavirus
      (HPV) positive and HPV-Negative tonsillar and base of tongue cancer.
AB  - AIM: To examine LMP10 expression and its possible impact on clinical outcome in
      human papillomavirus (HPV) positive and HPV-negative tonsillar and base of tongue
      squamous cell carcinoma (TSCC and BOTSCC). BACKGROUND: Outcome is better in HPV
      positive TSCC and BOTSCC compared to matching HPV-negative tumours, with roughly
      80% vs. 40% 5-year disease free survival (DFS) with less aggressive treatment
      than today's chemoradiotherapy. Since current treatment often results in harmful
      side effects, less intensive therapy, with sustained patient survival would be an
      attractive alternative. However, other markers together with HPV status are
      necessary to select patients and for this purpose LMP10 expression is
      investigated here in parallel to HPV status and clinical outcome. MATERIALS AND
      METHODS: From 385 patients diagnosed between 2000 and 2007 at the Karolinska
      University Hospital, 278 formalin fixed paraffin embedded TSCC and BOTSCC
      biopsies, with known HPV DNA status, were tested for LMP10 nuclear and
      cytoplasmic expression (fraction of positive cells and staining intensity). The
      data was then correlated to clinical outcome. RESULTS: An absent/low compared to
      a moderate/high LMP10 nuclear fraction of positive cells was correlated to a
      better 3-year DFS in the HPV-positive group of patients (log-rank p = 0.005), but
      not in the HPV-negative group. In the HPV-negative group of patients, in contrast
      to the HPV-positive group, moderate/high LMP10 cytoplasmic fraction and
      weak/moderate/high LMP10 cytoplasmic intensity correlated to a better 3-year DFS
      (p = 0.003 and p = 0.001) and 3-year overall survival (p = 0.001 and 0.009).
      CONCLUSION: LMP10 nuclear expression in the HPV-positive group and LMP10
      cytoplasmic expression in the HPV-negative group of patients correlated to better
      clinical outcome.

PMID- 24752329
TI  - Scaling up stomatal conductance from leaf to canopy using a dual-leaf model for
      estimating crop evapotranspiration.
AB  - The dual-source Shuttleworth-Wallace model has been widely used to estimate and
      partition crop evapotranspiration (lambdaET). Canopy stomatal conductance (Gsc),
      an essential parameter of the model, is often calculated by scaling up leaf
      stomatal conductance, considering the canopy as one single leaf in a so-called
      "big-leaf" model. However, Gsc can be overestimated or underestimated depending
      on leaf area index level in the big-leaf model, due to a non-linear stomatal
      response to light. A dual-leaf model, scaling up Gsc from leaf to canopy, was
      developed in this study. The non-linear stomata-light relationship was
      incorporated by dividing the canopy into sunlit and shaded fractions and
      calculating each fraction separately according to absorbed irradiances. The model
      includes: (1) the absorbed irradiance, determined by separately integrating the
      sunlit and shaded leaves with consideration of both beam and diffuse radiation;
      (2) leaf area for the sunlit and shaded fractions; and (3) a leaf conductance
      model that accounts for the response of stomata to PAR, vapor pressure deficit
      and available soil water. In contrast to the significant errors of Gsc in the big
      leaf model, the predicted Gsc using the dual-leaf model had a high degree of data
      model agreement; the slope of the linear regression between daytime predictions
      and measurements was 1.01 (R2 = 0.98), with RMSE of 0.6120 mm s-1 for four clear
      sky days in different growth stages. The estimates of half-hourly lambdaET using
      the dual-source dual-leaf model (DSDL) agreed well with measurements and the
      error was within 5% during two growing seasons of maize with differing
      hydrometeorological and management strategies. Moreover, the estimates of soil
      evaporation using the DSDL model closely matched actual measurements. Our results
      indicate that the DSDL model can produce more accurate estimation of Gsc and
      lambdaET, compared to the big-leaf model, and thus is an effective alternative
      approach for estimating and partitioning lambdaET. 

PMID- 24752328
TI  - Mesenchymal stem cell priming: fine-tuning adhesion and function.
AB  - There is significant interest in the use of mesenchymal stem cells (MSCs) as a
      potential therapeutic modality in disease and disorder, particularly those with
      an inflammation-based component such as coronary, renal and hepatic diseases.
      While there is no question that MSCs possess the capability to manipulate an
      ongoing inflammatory injury, the recruitment of these cells to injured sites is
      generally poor, and thus, open to manipulation. Enhancing the localised
      recruitment of MSCs to injured tissues may enhance the efficiency and efficacy of
      this mode of therapy. A number of techniques exist in the literature to improve
      the recruitment of MSCs to injured tissues, including the use of cytokines,
      chemical modifications and coating with either synthetic or biological particles.
      In addition to enhancing MSC recruitment, there is an increasing body of work
      examining techniques which may enhance the anti-inflammatory activity of these
      cells. This review will summarise the literature around these topics. This first
      section of this review summarises the current literature with regard to MSC
      homing and their recruitment during conditions of injury. In relation to the anti
      inflammatory activity of MSCs, the role of systemic versus local activity will be
      discussed. The second part of the review focuses on the role of pretreatments in
      MSC therapy and how these may have potential for not only enhancing the
      recruitment of MSCs, but also their anti-inflammatory capabilities. In summary,
      it is clear that there is significant potential to improve the efficiency of MSC
      therapy and the techniques discussed in this review may be central to this in the
      future. 

PMID- 24752330
TI  - Information provision for people with multiple sclerosis.
AB  - BACKGROUND: People with multiple sclerosis (MS) are confronted with a number of
      important uncertainties concerning many aspects of the disease. Among others,
      these include diagnosis, prognosis, disease course, disease-modifying therapies,
      symptomatic therapies and non-pharmacological interventions. It has been shown
      that people with MS demand adequate information to be able to actively
      participate in medical decision making and to self-manage their disease. On the
      other hand, it has been found that patients' disease-related knowledge is poor.
      Therefore, guidelines have recommended clear and concise high-quality information
      at all stages of the disease. Several studies have outlined communication and
      information deficits in the care of people with MS and, accordingly, a number of
      information and decision support programmes have been published. OBJECTIVES: To
      evaluate the effectiveness of information provision interventions for people with
      MS that aim to promote informed choice and improve patient-relevant outcomes.
      SEARCH METHODS: We searched the Cochrane Multiple Sclerosis and Rare Diseases of
      the Central Nervous System Group Specialised Register which contains trials from
      CENTRAL (The Cochrane Library 2013, Issue 6), MEDLINE, EMBASE, CINAHL, LILACS,
      PEDro and clinical trials registries (12 June 2013) as well as other sources. In
      addition, we searched PsycINFO, trial registries, and reference lists of
      identified articles. We also contacted trialists. SELECTION CRITERIA: Randomised
      controlled trials, cluster randomised controlled trials and quasi-randomised
      trials comparing information provision for people with MS or suspected MS
      (intervention groups) with usual care or other types of information provision
      (control groups) were eligible. DATA COLLECTION AND ANALYSIS: Two review authors
      independently assessed the retrieved articles for relevance and methodological
      quality, and extracted data. Critical appraisal of studies addressed the risk of
      selection bias, performance bias, attrition bias and detection bias. We contacted
      authors of relevant studies for additional information. MAIN RESULTS: Ten
      randomised controlled trials involving a total of 1314 participants met the
      inclusion criteria and were analysed. The interventions addressed a variety of
      topics using different approaches for information provision in different
      settings. Topics included disease-modifying therapy, relapse management, self
      care strategies, fatigue management, family planning and general health
      promotion. The interventions contained decision aids, educational programmes,
      self-care interventions and personal interviews with physicians. All
      interventions were complex interventions using more than one active component,
      but the number and extent of the intervention components differed markedly
      between studies. The studies had a variable risk of bias. We did not perform meta
      analyses due to marked clinical heterogeneity. All four studies assessing MS
      related knowledge (524 participants; moderate-quality evidence) detected
      significant differences between groups as a result of the interventions
      indicating that information provision may successfully increase participants'
      knowledge. There were mixed results from four studies reporting effects on
      decision making (836 participants; low-quality evidence) and from five studies
      assessing quality of life (605 participants; low-quality evidence). There were no
      adverse events in the six studies reporting on adverse events. AUTHORS'
      CONCLUSIONS: Information provision for people with MS seems to increase disease
      related knowledge, with less clear results on decision making and quality of
      life. There seem to be no negative side effects from informing patients about
      their disease. Interpretation of study results remains challenging due to the
      marked heterogeneity of the interventions and outcome measures.

PMID- 24752331
TI  - Histological analysis of SLC38A6 (SNAT6) expression in mouse brain shows
      selective expression in excitatory neurons with high expression in the synapses.
AB  - SLC38A6 is one of the newly found members of the solute carrier 38 family
      consisting of total 11 members, of which only 6 have been characterized so far.
      Being the only glutamine transporter family expressed in the brain, this family
      of proteins are most probably involved in the regulation of the glutamate
      glutamine cycle, responsible for preventing excitotoxicity. We used
      immunohistochemistry to show that SLC38A6 is primarily expressed in excitatory
      neurons and is not expressed in the astrocytes. Using proximity ligation assay,
      we have quantified the interactions of this SLC38 family protein with other
      proteins with known localization in the cells, showing that this transporter is
      expressed at the synapses. Moreover, this study has enabled us to come up with a
      model suggesting sub-cellular localization of SLC38A6 at the synaptic membrane of
      the excitatory neurons. 

PMID- 24752332
TI  - Facile synthesis of asymmetric Ag-organosilica hybrid nanoparticles with tunable
      morphologies and optical properties.
AB  - This study reports a simple and novel wet-chemical method for synthesizing
      asymmetric Ag-organosilica hybrid nanoparticles with finely-tuned morphologies
      and optical properties. 

PMID- 24752334
TI  - Extending FRET cascades on linear DNA photonic wires.
AB  - Photonic wires were constructed by sequentially arranging up to 7 fluorophores
      along a concatenated DNA scaffold. This yielded nanostructures displaying from
      one- to six-energy transfer steps where end-to-end efficiency reflected the
      multiple underlying photophysical processes and the ability of long-range
      interactions to compensate for localized non-ideal dye behaviour. 

PMID- 24752333
TI  - Anti-VEGF-A affects the angiogenic properties of tumor-derived microparticles.
AB  - Tumor derived microparticles (TMPs) have recently been shown to contribute to
      tumor re-growth partially by inducing the mobilization and tumor homing of
      specific bone marrow derived pro-angiogenic cells (BMDCs). Since antiangiogenic
      drugs block proangiogenic BMDC mobilization and tumor homing, we asked whether
      TMPs from cells exposed to an antiangiogenic drug may affect BMDC activity and
      trafficking. Here we show that the level of VEGF-A is reduced in TMPs from EMT/6
      breast carcinoma cells exposed to the anti-VEGF-A antibody, B20. Consequently,
      these TMPs exhibit reduced angiogenic potential as evaluated by a Matrigel plug
      and Boyden chamber assays. Consistently, BMDC mobilization, tumor angiogenesis,
      microvessel density and BMDC-colonization in growing tumors are reduced in mice
      inoculated with TMPs from B20-exposed cells as compared to mice inoculated with
      control TMPs. Collectively, our results suggest that the neutralization of VEGF-A
      in cultured tumor cells can block TMP-induced BMDC mobilization and colonization
      of tumors and hence provide another mechanism of action by which antiangiogenic
      drugs act to inhibit tumor growth and angiogenesis. 

PMID- 24752336
TI  - Changing ecosystem service values following technological change.
AB  - Research on ecosystem services has focused mostly on natural areas or remote
      places, with less attention given to urban ecosystem services and their
      relationship with technological change. However, recent work by urban ecologists
      and urban designers has more closely examined and appreciated the opportunities
      associated with integrating natural and built infrastructures. Nevertheless, a
      perception remains in the literature on ecosystem services that technology may
      easily and irreversibly substitute for services previously obtained from
      ecosystems, especially when the superiority of the engineered system motivated
      replacement in the first place. We emphasize that the expected tradeoff between
      natural and manufactured capital is false. Rather, as argued in other contexts,
      the adoption of new technologies is complementary to ecosystem management. The
      complementarity of ecosystem services and technology is illustrated with a case
      study in Barcelona, Spain where the installation of sophisticated water treatment
      technology increased the value of the ecosystem services found there.
      Interestingly, the complementarity between natural and built infrastructures may
      remain even for the very ecosystems that are affected by the technological
      change. This finding suggests that we can expect the value of ecosystem services
      to co-evolve with new technologies. Technological innovation can generate new
      opportunities to harness value from ecosystems, and the engineered structures
      found in cities may generate more reliance on ecosystem processes, not less. 

PMID- 24752335
TI  - Management of acquired resistance to epidermal growth factor receptor kinase
      inhibitors in patients with advanced non-small cell lung cancer.
AB  - The widespread adoption of epidermal growth factor receptor (EGFR) tyrosine
      kinase inhibitors for the first-line treatment of patients with advanced EGFR
      mutated non-small cell lung cancer has resulted in acquired tyrosine kinase
      inhibitor resistance becoming a ubiquitous clinical problem. The identification
      of specific mechanisms of acquired resistance has allowed a better understanding
      of the biology and natural history of resistant disease, but is only now starting
      to impact treatment decisions. Strategies for managing acquired resistance in
      patients with advanced non-small cell lung cancer are complex and must be adapted
      to the individual characteristics of each patient's cancer. Although combination
      chemotherapy is the presumed standard of care for most patients, prospective
      trial data are lacking, highlighting the importance of offering patients
      participation in clinical trials in this setting. Emerging data from trials of
      third-generation mutant-specific EGFR kinase inhibitors suggests particular
      promise with this class of agents.

PMID- 24752337
TI  - The expression patterns of p53 and p16 and an analysis of a possible role of HPV
      in primary adenocarcinoma of the urinary bladder.
AB  - BACKGROUND: Primary adenocarcinoma of the urinary bladder is rare. The molecular
      and cellular events leading to its pathogenesis are not well delineated. The goal
      of this study was to investigate p53 and p16 expression, as well as HPV status,
      in a relatively large series of primary bladder adenocarcinomas. MATERIALS AND
      METHODS: Thirty six cases of urinary bladder adenocarcinoma were chosen from
      participating institutions. The diagnosis and available clinical history were
      reviewed in each case. Immunostains for p53, p16 and HPV and high-risk and low
      risk HPV-ISH were performed on all tumors. RESULTS: Patients had an average age
      of 61 years with a male predominance (1.5 ? 1 male ? female ratio). The average
      tumor size in cystectomy specimens was 4.3 cm. Of the cases managed by
      transurethral resection, 40% were pT2 at the time of diagnosis. In cystectomy
      specimens, 77% were either pT3 or pT4. Strong nuclear p16 expression was seen in
      67% of all cases and p53 expression was present in 58% of the cases. Expression
      of both markers was seen in 33% of cases. Expression of p16 or p53 alone was
      present in 12 (33%) and 9 (25%) cases, respectively. Neither marker was expressed
      in only 3 (8%) of the tumors. No significant correlation between clinical
      variables and any of the markers we studied was identified. No HPV infection was
      detected in any case. CONCLUSIONS: Expression of p53 and/or p16 is very common in
      urinary bladder adenocarcinoma. These findings implicate a high likelihood that
      alterations in these cell cycle proteins contribute to the pathogenesis of these
      tumors. Despite frequent immunohistochemical labeling for p16, no evidence of HPV
      infection was found.

PMID- 24752338
TI  - SOX2 oncogenes amplified and operate to activate AKT signaling in gastric cancer
      and predict immunotherapy responsiveness.
AB  - INTRODUCTION: Gastric cancer is the second leading cause of cancer mortality in
      the world. Whether the oncogene, amplified on chromosome 3q26, SOX2, a master
      transcriptional regulator of stemness, operate to drive strong growth phenotype
      in gastric cancer were unknown. MATERIALS AND METHODS: The gene expression
      changes of SOX2 in human gastric cancer tissues compared with non-cancerous
      tissues was detected using real-time quantitative reverse transcriptase
      polymerase chain reaction (QRT-PCR) analysis and immunohistochemistry, which
      identified the gene overexpression of SOX2 in gastric cancer. Moreover, we
      discovered that SOX2 promoted cancer cell proliferation in vitro/vivo and SOX2
      expression correlated with elevated AKT phosphorylation in gastric cancer, while
      the AKT phosphorylation was required for SOX2's oncogenic effects. Next, our data
      point to the usefulness of SOX2 overexpression, as a new predictive marker for
      responsiveness to trastuzumab. CONCLUSION: SOX2 is a commonly activated tumor
      promoter that activate AKT signaling in gastric cancer and a new predictive
      marker for targeted therapy.

PMID- 24752339
TI  - Transarterial (chemo)embolization for curative resection of hepatocellular
      carcinoma: a systematic review and meta-analyses.
AB  - PURPOSE: To assess the beneficial and harmful effects of transarterial
      embolization (TAE) or transarterial chemoembolization (TACE) for curative
      resection of hepatocellular carcinoma (HCC). METHODS: The authors conducted an
      extensive search of studies on this strategy. All randomized controlled trials
      comparing TACE or TAE plus operation versus operation only were considered for
      inclusion, regardless of blinding, language, or publication status. Results were
      performed with disease-free survival (DFS) and overall survival (OS) as the
      primary endpoint. Tumor response and adverse events were secondary endpoints.
      RESULTS: A total of 10 studies involving 909 HCC participants finally fulfilled
      the predefined inclusion criteria. Four trials assessed preoperative TACE versus
      control and six trials assessed postoperative TACE versus control. There were
      significant improvements for DFS [HR 0.62 (95 % CI 0.49-0.79)] and OS [HR 0.60
      (0.46-0.79)] in the postoperative TACE compared with the control when the mean
      tumor size was bigger than 5 cm. However, preoperative TACE did not improve DFS
      [HR 0.92 (0.71-1.20)] and OS [HR 1.07 (0.78-1.46)] for curative resection of HCC.
      Substantial differences in criteria for assessing tumor response did not allow
      quantitative analyses. Fever (26.7-85.9 %), abdominal pain (19.3-71.2 %), and
      nausea/vomiting (27.4-66.3 %) were common adverse events. Relatively rare but
      more serious complications were also reported. CONCLUSIONS: Postoperative TACE
      offers potential benefits for curative resection of HCC when the mean tumor size
      is bigger than 5 cm.

PMID- 24752340
TI  - Active surveillance for metastatic or recurrent renal cell carcinoma.
AB  - PURPOSE: Metastatic renal cell carcinoma (mRCC) sometimes presents with an
      indolent course without any significant symptoms. Here, the potential impact of
      active surveillance (AS) on clinical outcomes in asymptomatic or minimally
      symptomatic mRCC patients was retrospectively evaluated. METHODS: mRCC patients
      who were followed up with deferred treatment for the purpose of AS between 2000
      and 2012 were enrolled. Patient and disease characteristics, outcomes of AS and
      subsequent therapies, and predictive factors for rapid disease progression were
      analyzed. The primary endpoint was time-to-progression (TTP). RESULTS: First-line
      systemic therapy was deliberately deferred in 58 patients. During AS, the best
      overall responses were stable disease for 48 patients (83 %) and progressive
      disease (PD) for 10 patients (17 %), and 47 patients ultimately experienced
      disease progression at the time of data cutoff. With a median follow-up of 31.4
      months, the median TTP was 12.4 months (95 % confidence interval 8.4-16.5) and
      median overall survival was not reached. After univariate and multivariate
      analyses for TTP, Karnofsky performance status <100 %, liver metastasis, and a
      time from diagnosis to AS of less than 1 year were found to be predictive factors
      for a shorter TTP. After PD, 30 patients received systemic treatment (14
      sunitinib, 11 pazopanib, 4 immunotherapy, and 1 temsirolimus). The objective
      response rates were 71 % for sunitinib and 46 % for pazopanib, which were deemed
      comparable with historical controls. CONCLUSIONS: Asymptomatic or minimally
      symptomatic mRCC patients can be observed for a prolonged period of time without
      active treatment.

PMID- 24752342
TI  - CMS--engaging multiple payers in payment reform.

PMID- 24752341
TI  - Development of a cell-based assay measuring the activation of FcgammaRIIa for the
      characterization of therapeutic monoclonal antibodies.
AB  - Antibody-dependent cellular cytotoxicity (ADCC) is one of the important
      mechanisms of action of the targeting of tumor cells by therapeutic monoclonal
      antibodies (mAbs). Among the human Fcgamma receptors (FcgammaRs), FcgammaRIIIa is
      well known as the only receptor expressed in natural killer (NK) cells, and it
      plays a pivotal role in ADCC by IgG1-subclass mAbs. In addition, the
      contributions of FcgammaRIIa to mAb-mediated cytotoxicity have been reported.
      FcgammaRIIa is expressed in myeloid effector cells including neutrophils and
      macrophages, and it is involved in the activation of these effector cells.
      However, the measurement of the cytotoxicity via FcgammaRIIa-expressing effector
      cells is complicated and inconvenient for the characterization of therapeutic
      mAbs. Here we report the development of a cell-based assay using a human
      FcgammaRIIa-expressing reporter cell line. The FcgammaRIIa reporter cell assay
      was able to estimate the activation of FcgammaRIIa by antigen-bound mAbs by a
      very simple method in vitro. The usefulness of this assay for evaluating the
      activity of mAbs with different abilities to activate FcgammaRIIa was confirmed
      by the examples including the comparison of the activity of the anti-CD20 mAb
      rituximab and its Fc-engineered variants, and two anti-EGFR mAbs with different
      IgG subclasses, cetuximab (IgG1) and panitumumab (IgG2). We also applied this
      assay to the characterization of a force-oxidized mAb, and we observed that
      oxidation significantly decreased the FcgammaRIIa activation by EGFR-bound
      cetuximab. These results suggest that our FcgammaRIIa reporter assay is a
      promising tool for the characterization of therapeutic mAbs, including Fc
      engineered mAbs, IgG2-subclass mAbs, and their product-related variants. 

PMID- 24752343
TI  - New kids on the block: novel informatics methods for natural product discovery.
AB  - Covering: 2008 to 2014 Mass spectrometry is a key technology for the
      identification and structural elucidation of natural products. Manual
      interpretation of the resulting data is tedious and time-consuming, so methods
      for automated analysis are highly sought after. In this review, we focus on four
      recently developed methods for the detection and investigation of small
      molecules, namely MetFrag/MetFusion, ISIS, FingerID, and FT-BLAST. These methods
      have the potential to significantly advance the field of computational mass
      spectrometry for the research of natural products. For example, they may help
      with the dereplication of compounds at an early stage of the drug discovery
      process; that is, the detection of molecules that are identical or highly similar
      to known drugs or drug leads. Furthermore, when a potential drug lead has been
      determined, these tools may help to identify it and elucidate its structure.

PMID- 24752344
TI  - Spontaneous ankylosis in erosive osteoarthritis of the finger joints: a case
      series of eight postmenopausal women.
AB  - Osteoarthritis of the hands is very common, particularly in elderly people.
      Little is known though, is the subset of erosive osteoarthritis (EOA), which
      predicts a poorer prognosis and causes much more discomfort. Even less known is
      the fact that this subset can evolve into spontaneous ankylosis. We describe
      eight women (average age 62.6, range 54-74 years) with EOA and spontaneous
      ankylosis of the proximal interphalangeal (PIP) and/or distal interphalangeal
      (DIP) joints. In total, 21 PIP joints (0-7 per patient) were found with EOA and
      nine PIP joints (0-3 per patient) with ankylosis. In one patient, ankylosis of
      the PIP was already seen at the first presentation. In the other cases, it took
      an average of 77.4 months (range 34-119) for EOA to develop into ankylosis of the
      PIP. For DIP joints, the numbers were 17 joints (1-4 per patient) with EOA and
      three joints (0-1 per patient) with ankylosis, respectively. In one patient,
      ankylosis of the DIP was already seen at the first presentation. Ankylosis was
      found significantly more often on the left hand (n = 10) compared to the right
      hand (n = 2; p < 0.0005), while all the patients were right handed. No difference
      in handedness was found for the occurrence of EOA. Although rare, PIP or DIP
      joint with EOA can-over the course of several painful years-develop into a
      spontaneous pain-free ankylosis. Ankylosis was more commonly found in the left
      hand than in the right hand, probably due right handedness. 

PMID- 24752345
TI  - Responsiveness of the EuroQol EQ-5D and Hospital Anxiety and Depression Scale
      (HADS) in rheumatoid arthritis patients receiving tocilizumab.
AB  - The aim of this study was to assess the responsiveness to change of the quality
      of life evaluated by the EuroQol Five Dimensions Questionnaire (EQ-5D) and
      Hospital Anxiety and Depression Scale (HADS) after biological treatment in a
      population of rheumatoid arthritis patients. A cohort of patients with RA (n =
      29) treated with tocilizumab (TCZ) were analyzed in the study. The inclusion
      criteria were patients aged between 18 and 65 years, fulfilling American College
      of Rheumatology 1987 criteria for RA. All patients had inadequate response to
      methotrexate and with no prior biologic exposure. They were evaluated clinically
      including Disease Activity Score 28 (DAS28), and the European Quality of Life 5
      Dimensions (EQ-5D) to measure the quality of life, and HAD assessed the anxiety
      and depression status at the initiation of treatment with anti-IL 6 receptor
      antibody agent and after 6 months. Sensitivity to change was quantified by the
      effect size (ES) before and after the treatment with TCZ. Among 29 patients with
      RA included in the study, 25 were females and 4 males. The mean age was 42 years
      +/- 13.4 (SD). Three patients were excluded from the study before 24 weeks
      because of serious side effects, and five have missing data. The study population
      exhibited significant decreases in all measures of disease activity at 24 weeks.
      Physical activity expressed by the Health Assessment Questionnaire (HAQ) score
      increased through the observation period (for all p < 0.001). Sensitivity to
      change was high for the VAS and EQ-5D (ES 1.58 and 1.36, respectively) but only
      moderate for the HAD anxiety component (ES = 0.70) and small for the HAD
      depression component (ES = 0.4). The EQ-5D and VAS were more responsive than HADS
      to evaluate the quality of life on patient with RA treated with TCZ. 

PMID- 24752346
TI  - Impact of anti-centromere antibodies on pulmonary function test results in
      patients with systemic sclerosis without established or suspected pulmonary
      disease.
AB  - Pulmonary arterial hypertension (PAH) occurs in approximately 15% of patients
      with systemic sclerosis (SSc). Annual screening with pulmonary function tests
      (PFT) is recommended to help identify those patients at risk of PAH. We have
      noted that patients with SSc who carry anti-centromere autoantibodies (ACA) often
      have PFT abnormalities, in the absence of clinical evidence of PAH. To evaluate
      this further, we undertook a retrospective case-control study evaluating PFT
      results in patients with SSc in whom pulmonary complications have neither been
      diagnosed nor suspected. Patients were divided according to ACA carriage and
      groups compared for PFT results. The median forced vital capacity (FVC) was
      higher in ACA-positive patients (106 vs. 93%, p=0.004). The gas transfer factor
      (TLco) was significantly lower in the ACA group (62.5 vs. 71%, p=0.013). The
      resulting FVC:TLco was significantly higher for ACA-positive vs. ACA-negative
      patients with SSc (1.70 vs. 1.29, p<0.001). Our findings suggest patients
      carrying ACA, without established or suspected pulmonary complications, have PFT
      abnormalities consistent with indolent increased pulmonary vascular resistance
      despite the majority of such patients not subsequently developing PAH. The long
      term sequelae of PFT abnormalities in those patients with ACA who do not
      subsequently develop PAH are unknown.

PMID- 24752347
TI  - ANCA-associated vasculitis in Hispanic Americans: an unrecognized severity.
AB  - This study aims to compare the severity and outcomes of antineutrophil
      cytoplasmic antibody (ANCA)-associated vasculitis (AAV) between Hispanics and
      Caucasians living in the same geographical area. All patients diagnosed with AAV
      at two academic institutions in Chicago from January 2006 to December 2012 were
      retrospectively and prospectively identified. Disease activity was measured with
      the Birmingham Vasculitis Activity Score (BVAS), and disease damage was measured
      with the Vasculitis Damage Index (VDI). Student's t test and chi-square tests
      were employed; p <= 0.05 was considered significant. Seventy patients with AAV
      were identified; 15 patients were excluded. Fifty-five patients were included in
      the study: 23 Hispanics and 32 Caucasians, 35 patients with granulomatosis with
      polyangiitis (Wegener's), 12 with microscopic polyangiitis, 7 with eosinophilic
      granulomatosis with polyangiitis, and 1 with renal-limited vasculitis. Compared
      to Caucasians, Hispanics had a higher BVAS at presentation (16.3 +/- 7.6 versus
      10.7 +/- 7.5, p = 0.006), a higher VDI at presentation (2.90 +/- 1.50 versus 2.06
      +/- 1.30, p = 0.030), and a cumulative VDI (3.90 +/- 1.70 versus 2.50 +/- 1.90, p
      = 0.010). Renal involvement was more common among Hispanics (85 % of Hispanics
      versus 48 % of Caucasians, p = 0.01). Seventy percent of Hispanics had acute
      renal failure (mean creatinine = 3.37 +/- 4.4 mg/dl) of whom seven (50 %)
      required dialysis, versus 25 % of Caucasians (mean creatinine = 1.78 +/- 1.57
      mg/dl, p = 0.03) and only two requiring dialysis. Compared to Caucasians,
      Hispanics with AAV present with more severe disease and higher damage indices.
      Larger studies are required to confirm these findings and delineate the
      respective roles of environment and genetics in the pathogenesis of the disease.

PMID- 24752348
TI  - Heart rate, conduction and ultrasound abnormalities in adults with joint
      hypermobility syndrome/Ehlers-Danlos syndrome, hypermobility type.
AB  - Joint hypermobility syndrome (JHS) and Ehlers-Danlos syndrome, hypermobility type
      (EDS-HT) are two clinically overlapping heritable connective tissue disorders
      strongly associating with pain, fatigue and other secondary aspects. Though not
      considered a diagnostic criterion for most EDS subtypes, cardiovascular
      involvement is a well-known complication in EDS. A case-control study was carried
      out on 28 adults with JHS/EDS-HT diagnosed according to current criteria,
      compared to 29 healthy subjects evaluating resting electrocardiographic (ECG), 24
      h ECG and resting heart ultrasound data. Results obtained in the ECG studies
      showed a moderate excess in duration of the PR interval and P wave, an excess of
      heart conduction and rate abnormalities and an increased rate of mitral and
      tricuspid valve insufficiency often complicating with "true" mitral valve
      prolapse in the ecocardiographic study. These variable ECG subclinical anomalies
      reported in our sample may represent the resting surrogate of such a subnormal
      cardiovascular response to postural changes that are known to be present in
      patients with JHS/EDS-HT. Our findings indicate the usefulness of a full
      cardiologic evaluation of adults with JHS/EDS-HT for the correct management. 

PMID- 24752349
TI  - IL-17, a potential therapeutic target for Sjogren's syndrome?

PMID- 24752350
TI  - Progress made towards enhancement of rheumatology education and practice in
      Zambia: review of an ILAR-supported project.
AB  - The burden of non-communicable diseases such as musculoskeletal diseases in the
      developing world is often overshadowed by the more prevalent infectious diseases.
      Generally, there is gross underestimation of the burden of rheumatologic disease
      in the backdrop of scanty or indeed non-existent rheumatology services in these
      countries. Local studies conducted in the last two decades in Zambia have
      documented the increasing burden of rheumatologic conditions in the country.
      There are unfortunately negligible rheumatology services in the country both at
      tertiary or primary health-care facility levels. There is thus an urgent need to
      build capacity for these services so as to improve the care and management of
      rheumatic conditions. Here, we review progress made by an International League of
      Associations for Rheumatology (ILAR)-supported project that has run for the past
      2 years (2012-2013) with the objective of enhancing paediatric and adult
      rheumatology education and practice so as to stimulate positive change in
      practice and related care services in Zambia. During this short time of the
      project, substantial progress has been made in the areas of paediatric and adult
      rheumatology services enhancement at the University Teaching Hospital, Lusaka:
      streamlining of referrals and follow-ups of rheumatology patients, laying
      foundations for short- and long-term medical education in rheumatology and
      raising public awareness of rheumatic diseases. The progress made by this grant
      underscores the suitability of the ILAR mission statement "think global, act
      local" demonstrating that even with minimum resources and networking, improvement
      of rheumatology care in developing countries is attainable.

PMID- 24752352
TI  - IL-6 upregulates a disintegrin and metalloproteinase with thrombospondin motifs 2
      (ADAMTS-2) in human osteosarcoma cells mediated by JNK pathway.
AB  - ADAMTS-2 and ADAMTS-3 (a disintegrin and metalloproteinase with thrombospondin
      type 1 motif 2) belong to the procollagen aminoproteinase subfamily of ADAMTS
      proteases. They play crucial roles in the collagen metabolism. To understand the
      regulation of ADAMTS-2 gene expression in osteoblastic cells, we have cloned a
      functional 760 bp of human ADAMTS-2 promoter. Sequence analysis of the ADAMTS-2
      promoter region showed the absence of a TATA box, but identified a GC box, a CpG
      island, several GAGA boxes and several transcriptional factor binding sites,
      which may be valuable in the regulation of ADAMTS-2 transcription. We also
      elucidated that Interleukin 6 (IL-6) increases ADAMTS-2 and ADAMTS-3 mRNA and
      protein levels in different osteosarcoma cell lines namely, MG-63 and Saos-2. IL
      6 also increases the transcriptional activation of the ADAMTS-2 gene promoter.
      Pathway inhibition studies revealed that ADAMTS-2 upregulation by IL-6 was
      mediated by JNK pathway. 

PMID- 24752351
TI  - Estrogen improves the proliferation and differentiation of hBMSCs derived from
      postmenopausal osteoporosis through notch signaling pathway.
AB  - Estrogen deficiency is the main reason of bone loss, leading to postmenopausal
      osteoporosis, and estrogen replacement therapy (ERT) has been demonstrated to
      protect bone loss efficiently. Notch signaling controls proliferation and
      differentiation of bone marrow-derived mesenchymal stem cells (BMSCs). Moreover,
      imperfect estrogen-responsive elements (EREs) were found in the 5'-untranslated
      region of Notch1 and Jagged1. Thus, we examined the molecular and biological
      links between estrogen and the Notch signaling in postmenopausal osteoporosis in
      vitro. hBMSCs were obtained from healthy women and patients with postmenopausal
      osteoporosis. Notch signaling molecules were quantified using real-time
      polymerase chain reaction (real-time PCR) and Western Blot. Luciferase reporter
      constructs with putative EREs were transfected into hBMSCs and analyzed. hBMSCs
      were transduced with lentiviral vectors containing human Notch1 intracellular
      domain (NICD1). We also used N-[N-(3, 5-diflurophenylacetate)-l-alanyl]-(S)
      phenylglycine t-butyl ester, a gamma-secretase inhibitor, to suppress the Notch
      signaling. We found that estrogen enhanced the Notch signaling in hBMSCs by
      promoting the expression of Jagged1. hBMSCs cultured with estrogen resulted in
      the up-regulation of Notch signaling and increased proliferation and
      differentiation. Enhanced Notch signaling could enhance the proliferation and
      differentiation of hBMSCs from patients with postmenopausal osteoporosis (OP
      hBMSCs). Our results demonstrated that estrogen preserved bone mass partly by
      activating the Notch signaling. Because long-term ERT has been associated with
      several side effects, the Notch signaling could be a potential target for
      treating postmenopausal osteoporosis. 

PMID- 24752353
TI  - Some findings of FADD knockdown in inhibition of HIV-1 replication in Jurkat
      cells and PBMCs.
AB  - Fas-associated protein with death domain (FADD) is a key adaptor molecule
      transmitting the death signal mediated by death receptors, and it is also
      required for T cell proliferation. A recent study indicated that FADD is able to
      affect HIV-1 production, but the mechanism is not known. Using the susceptible
      Jurkat cell line and peripheral blood mononuclear cells, we studied the effects
      of FADD on HIV-1 production. TaqMan RT-PCR was used to quantify HIV-1 viral RNA
      copies, and Western blot analysis was used to detect protein expression. FADD
      knockdown decreased HIV-1 replication and inactivated caspase-3 activity in the
      cells and blocked CD4 translocation to the lipid rafts of the plasma membrane.
      Reduced expression of FADD suppressed TCR signaling through downregulation of
      TCR, CD3, and Zap-70 in response to HIV-1 infection and blocked the trafficking
      of TCR, CD3, CD28, and Zap-70 to lipid rafts, leading to reduced activation of NF
      kappaB and NFAT, which are required for HIV-1 replication. FADD knockdown
      diminished caspase-8 migration to lipid rafts and its expression in response to
      HIV-1 infection. These results indicate that FADD, as a host pro-apoptotic
      protein, plays important roles in regulating HIV-1 replication and production in
      several ways, and apoptotic pathway inhibition is able to decrease HIV-1
      replication and production. 

PMID- 24752355
TI  - An unusual cause of chronic diarrhea.

PMID- 24752356
TI  - Sound symbolism in the languages of Australia.
AB  - The notion that linguistic forms and meanings are related only by convention and
      not by any direct relationship between sounds and semantic concepts is a
      foundational principle of modern linguistics. Though the principle generally
      holds across the lexicon, systematic exceptions have been identified. These
      "sound symbolic" forms have been identified in lexical items and linguistic
      processes in many individual languages. This paper examines sound symbolism in
      the languages of Australia. We conduct a statistical investigation of the
      evidence for several common patterns of sound symbolism, using data from a sample
      of 120 languages. The patterns examined here include the association of meanings
      denoting "smallness" or "nearness" with front vowels or palatal consonants, and
      the association of meanings denoting "largeness" or "distance" with back vowels
      or velar consonants. Our results provide evidence for the expected associations
      of vowels and consonants with meanings of "smallness" and "proximity" in
      Australian languages. However, the patterns uncovered in this region are more
      complicated than predicted. Several sound-meaning relationships are only
      significant for segments in prominent positions in the word, and the prevailing
      mapping between vowel quality and magnitude meaning cannot be characterized by a
      simple link between gradients of magnitude and vowel F2, contrary to the claims
      of previous studies. 

PMID- 24752357
TI  - Ultrafast vapourization dynamics of laser-activated polymeric microcapsules.
AB  - Precision control of vapourization, both in space and time, has many potential
      applications; however, the physical mechanisms underlying controlled boiling are
      not well understood. The reason is the combined microscopic length scales and
      ultrashort timescales associated with the initiation and subsequent dynamical
      behaviour of the vapour bubbles formed. Here we study the nanoseconds vapour
      bubble dynamics of laser-heated single oil-filled microcapsules using coupled
      optical and acoustic detection. Pulsed laser excitation leads to vapour formation
      and collapse, and a simple physical model captures the observed radial dynamics
      and resulting acoustic pressures. Continuous wave laser excitation leads to a
      sequence of vapourization/condensation cycles, the result of absorbing
      microcapsule fragments moving in and out of the laser beam. A model incorporating
      thermal diffusion from the capsule shell into the oil core and surrounding water
      reveals the mechanisms behind the onset of vapourization. Excellent agreement is
      observed between the modelled dynamics and experiment. 

PMID- 24752354
TI  - CXCR4 is dispensable for T cell egress from chronically inflamed skin via the
      afferent lymph.
AB  - T cell recirculation through extralymphoid tissues is essential to immune
      surveillance, host defense and inflammation. In this process, T cells enter the
      tissue from the blood and subsequently leave via the afferent lymph. In the
      absence of inflammation, T cells require CCR7 expression to egress from the skin
      or lung, which is consistent with the constitutive expression of the CCR7 ligand
      CCL21 on lymphatic endothelium. However, during chronic inflammation alternative
      chemoattractants come into play, allowing Ccr7-deficient (Ccr7-/-) T cells to
      egress efficiently from affected skin. As T cell egress from inflamed sites is a
      potential control point of the inflammatory response, we aimed to determine
      alternative T cell exit receptors using a mouse and a sheep model. We show that
      CCR7+ and CCR7- T cells exiting from the chronically inflamed skin were highly
      responsive to the CXCR4 ligand CXCL12, which was induced in the lymphatics in the
      inflamed site. Based on these findings, we hypothesized that CXCR4 mediates T
      cell egress from inflamed skin. However, pharmacological inhibition of CXCR4 did
      not affect the tissue egress of wildtype or Ccr7-/- CD4 and CD8 T cells after
      adoptive transfer into chronically inflamed skin. Similarly, adoptively
      transferred Cxcr4-/- Ccr7-/- and Ccr7-/- T cells egressed from the inflamed skin
      equally well. Based on these data, we conclude that, while CXCR4 might play an
      essential role for other cell types that enter the afferent lymphatics, it is
      dispensable for T cell egress from the chronically inflamed skin. 

PMID- 24752358
TI  - Characteristics of dental morphology in the Xinjiang Uyghurs and correlation with
      the EDARV370A variant.
AB  - Teeth are one of the most important materials for anthropological studies because
      they are likely to be preserved in ancient remains. While the frequencies of
      dental characteristics can provide clues to the phylogeny of populations, genetic
      studies at the individual level can further reveal the biological mechanisms and
      evolutionary context of dental characteristics. In this study, by analyzing 38
      dental characteristics of 242 Xinjiang Uyghur individuals, we found that (i) the
      dental characteristics of the Uyghurs showed evidence of admixture between
      European and East Asian populations. The admixture proportions were in line with
      those previously reported in population genetic studies; (ii) the Xinjiang Uyghur
      dental characteristics formed three clusters in pairwise correlation analysis.
      One of the main clusters consisted of characteristics including incisor
      shoveling, double shoveling and mesial ridge; and (iii) all the characteristics
      in this cluster were significantly correlated with the genetic variant EDARV370A.
      The extracted composite phenotypic factor was also significantly associated with
      EDARV370A, which explained 18% of the total phenotypic variance. This indicated a
      pleiotropic effect, i.e., the same genetic factor affects a number of dental
      characteristics at the same time. Our results confirmed that EDARV370A, a genetic
      variant that first originated in East Asia about 30000 years ago, played an
      important role in incisor shoveling in East Asia. This finding suggested that
      incisor shoveling in modern humans in East Asia is likely to have appeared after
      the late Pleistocene.

PMID- 24752359
TI  - Puzzle out the regulation mechanism of PI4KIIalpha activity.

PMID- 24752360
TI  - Tragic knowledge: truth telling and the maintenance of hope in surgery.
AB  - Surgeons often are faced with the challenge of balancing truth telling and the
      maintenance of hope in the setting of a poor prognosis. This ethical dilemma is
      informed by conflicting appeals to principles of autonomy and nonmaleficence,
      where a patient's right to be told important medical information must be weighed
      against the potential harm that may result from the knowledge of an unfavourable
      diagnosis. Truth telling in surgery raises questions on the nature of truth
      itself, how much information ought to be shared, what information can be
      withheld, and how surgeons should share tragic knowledge with patients. This
      paper will address these questions and provide some insight on how surgeons may
      navigate the sharing of tragic knowledge. 

PMID- 24752361
TI  - A modification of radical antegrade modular pancreatosplenectomy for
      adenocarcinoma of the left pancreas: significance of en bloc resection including
      the anterior renal fascia.
AB  - BACKGROUND: Radical antegrade modular pancreatosplenectomy (RAMPS) has
      theoretical advantages for curative resection of adenocarcinomas of the left
      pancreas. The anterior renal fascia is a key structure, and resection planes
      should run posterior to this fascia. However, it is difficult to delineate this
      fascia and set a precise dissection plane. We modified RAMPS to achieve such a
      precise dissection plane with ease. METHODS: After clamping the splenic artery,
      the third duodenal portion was mobilized from the left to the right to locate the
      inferior vena cava, which was covered by the anterior renal fascia. Here, the
      anterior renal fascia was incised while approaching the dissection plane.
      Dissection then continued cephalad, with this plane along the inferior vena cava,
      and then turned along the left renal vein at the confluence of the left renal
      vein toward the renal hilum. At this point, dissection continued along the
      coronal plane to the superior edge of the pancreas. RESULTS: Between July 2007
      and December 2012, a total of 24 pancreatic adenocarcinoma patients underwent
      modified RAMPS. Tumor extension beyond the pancreatic parenchyma (T3) and lymph
      node metastases was confirmed in 17 and 13 cases, respectively. Histologically
      clear surgical margins were achieved (R0 resection) in 21 patients (88 %). The 5
      year overall survival rate was 53 %. Six patients survived for over 5 years
      without recurrence. CONCLUSIONS: This modification of RAMPS is advantageous for
      en bloc resection while actually including removal of the anterior renal fascia.
      It is associated with satisfactory survival rates for patients with distal
      pancreatic carcinomas.

PMID- 24752362
TI  - Sentinel node mapping in adenocarcinoma of the esophagogastric junction.
AB  - BACKGROUND: The incidence of adenocarcinoma of the esophagogastric junction (AEG)
      is increasing, but the surgical strategy for AEG remains controversial. We
      hypothesized that sentinel node (SN) mapping for AEG could be validated to avoid
      unnecessary lymphadenectomy and permit minimally invasive surgery. We examined
      the feasibility of SN mapping for AEG. METHODS: We enrolled 15 patients with
      preoperatively diagnosed cT1 N0 M0 primary AEG (Siewert type I, N = 3; Siewert
      type II, N = 12) lesions measuring <4 cm in diameter. The dual tracer method
      employing radioactive colloid and blue dye was used to detect SNs. The
      distribution of SNs was compared with that of metastatic lymph nodes in 52
      patients who were surgically treated without SN mapping. RESULTS: SNs were
      successfully identified in all the patients. Two patients with lymph node
      metastasis had positive SNs identified via an intraoperative pathological
      examination, and the diagnostic sensitivity and accuracy based on the SN status
      were both 100 %. For Siewert type II AEG, the SNs were not detected in the lower
      mediastinum by intraoperative gamma probing. Thus, all surgical procedures were
      performed via a transhiatal approach. No patient without SN metastasis
      experienced cancer recurrence during a 38-month median follow-up. The
      distribution of SNs was similar to that of lymph node metastasis in the patients
      who were surgically treated without SN mapping. CONCLUSIONS: We achieved 100 % SN
      detection. Our results suggested that SN mapping is feasible for AEG and highly
      sensitive and accurate in diagnosing lymph node metastasis. SN mapping may
      clarify the necessity of mediastinal lymph node dissection and individualize
      minimally invasive surgery.

PMID- 24752363
TI  - A comparative study of contrasting surgical residency programs.
AB  - BACKGROUND: Postgraduate training is completed in a 5-year surgical residency
      program in the USA, compared with 10 years in the UK. The UK Joint Committee on
      Surgical Training (JCST) has described quality indicators for surgical training.
      Similar indicators can be inferred from the American Board of Surgery and
      Accreditation Council for Graduate Medical Education. This exploratory study
      compares postgraduate surgical training between two regions following their
      respective national programs. METHODS: A questionnaire was developed based on
      JCST quality indicators. This was distributed electronically to all general
      surgical residents in the University of Pennsylvania (UPenn) (N = 64) and North
      and South West Thames general surgical registrars in London (N = 182). RESULTS: A
      total of 76 residents (31 %) completed the questionnaire and all data presented
      are self-reported. When residents operate electively, an attending is scrubbed
      for 57 % of cases in London versus 83 % at UPenn (p < 0.001). During emergency
      surgery, residents operate without an attending in the operating room (OR) for 60
      % of cases in London versus 2 % in UPenn (p < 0.001). London versus UPenn
      residents have a mean 3.6 versus 5.0 (p < 0.001) operating sessions and 0.7
      versus 2.3 (p < 0.001) teaching hours per week. In London, 68 % of residents have
      regular gastrointestinal endoscopy sessions compared with 39 % at UPenn (p =
      0.036). CONCLUSIONS: UPenn residents receive more supervised operating
      opportunities and scheduled teaching than their London counterparts. However,
      they have less independent operating experience and less exposure to
      gastrointestinal endoscopy training.

PMID- 24752364
TI  - Integrated graphene/nanoparticle hybrids for biological and electronic
      applications.
AB  - The development of novel graphene/nanoparticle hybrid materials is currently the
      subject of tremendous research interest. The intrinsic exceptional assets of both
      graphene (including graphene oxide and reduced graphene oxide) and nanoparticles
      render their hybrid materials synergic properties that can be useful in various
      applications. In this feature review, we highlight recent developments in
      graphene/nanoparticle hybrids and their promising potential in electronic and
      biological applications. First, the latest advances in synthetic methods for the
      preparation of the graphene/nanoparticle hybrids are introduced, with the
      emphasis on approaches to (1) decorate nanoparticles onto two-dimensional
      graphene and (2) wrap nanoparticles with graphene sheets. The pros and cons of
      large-scale synthesis are also discussed. Then, the state-of-the-art of
      graphene/nanoparticle hybrids in electronic and biological applications is
      reviewed. For electronic applications, we focus on the advantages of using these
      hybrids in transparent conducting films, as well as energy harvesting and
      storage. Biological applications, electrochemical biosensing, bioimaging, and
      drug delivery using the hybrids are showcased. Finally, the future research
      prospects and challenges in this rapidly developing area are discussed. 

PMID- 24752365
TI  - The lung microbiome of Ugandan HIV-infected pneumonia patients is compositionally
      and functionally distinct from that of San Franciscan patients.
AB  - Sub-Saharan Africa represents 69% of the total number of individuals living with
      HIV infection worldwide and 72% of AIDS deaths globally. Pulmonary infection is a
      common and frequently fatal complication, though little is known regarding the
      lower airway microbiome composition of this population. Our objectives were to
      characterize the lower airway microbiome of Ugandan HIV-infected patients with
      pneumonia, to determine relationships with demographic, clinical, immunological,
      and microbiological variables and to compare the composition and predicted
      metagenome of these communities to a comparable cohort of patients in the US (San
      Francisco). Bronchoalveolar lavage samples from a cohort of 60 Ugandan HIV
      infected patients with acute pneumonia were collected. Amplified 16S ribosomal
      RNA was profiled and aforementioned relationships examined. Ugandan airway
      microbiome composition and predicted metagenomic function were compared to US HIV
      infected pneumonia patients. Among the most common bacterial pulmonary pathogens,
      Pseudomonas aeruginosa was most prevalent in the Ugandan cohort. Patients with a
      richer and more diverse airway microbiome exhibited lower bacterial burden,
      enrichment of members of the Lachnospiraceae and sulfur-reducing bacteria and
      reduced expression of TNF-alpha and matrix metalloproteinase-9. Compared to San
      Franciscan patients, Ugandan airway microbiome was significantly richer, and
      compositionally distinct with predicted metagenomes that encoded a multitude of
      distinct pathogenic pathways e.g secretion systems. Ugandan pneumonia-associated
      airway microbiome is compositionally and functionally distinct from those
      detected in comparable patients in developed countries, a feature which may
      contribute to adverse outcomes in this population. 

PMID- 24752368
TI  - Faster the better: a reliable technique to sample anopluran lice in large hosts.
AB  - Among Anoplura, the family Echinophthiriidae includes those species that infest
      mainly the pinnipeds. Working with large hosts implies methodological
      considerations as the time spent in the sampling, and the way in that the animal
      is restrained. Previous works on echinophthiriids combined a diverse array of
      analyses including field counts of lice and in vitro observations. To collect
      lice, the authors used forceps, and each louse was collected individually. This
      implied a long manipulation time, i.e., ~60 min and the need to physically and/or
      chemically immobilize the animal. The present work described and discussed for
      the first a sample technique that minimized the manipulation time and also
      avoiding the use of anesthesia. This methodology implied combing the host's
      pelage with a fine-tooth plastic comb, as used in the treatment of human
      pediculosis, and keeping the comb with the lice retained in a Ziploc(r) bag with
      ethanol. This technique was used successfully in studies of population dynamic,
      habitat selection, and transmission pattern, being a reliable methodology. Lice
      are collected entirely and are in a good condition to prepare them for mounting
      for studying under light or scanning electron microscopy. Moreover, the use of
      the plastic comb protects from damaging taxonomically important structures as
      spines being also recommended to reach taxonomic or morphological goals. 

PMID- 24752367
TI  - The effect of 3-(biphenyl-4-yl)-3-hydoxyquinuclidine (BPQ-OH) and metronidazole
      on Trichomonas vaginalis: a comparative study.
AB  - Trichomonas vaginalis causes trichomoniasis in humans, a sexually transmitted
      disease commonly treated with metronidazole (MTZ), a drug that presents some
      toxicity, causing undesirable side effects. In addition, an increase in
      metronidazole-resistant parasites has been reported. Thus, the development of
      alternative treatment is recommended. To date, the search for antiparasitic drugs
      has been based on different approaches: identification of active natural
      products, identification of parasite targets, and the use of available compounds
      active against other pathogenic microorganisms. Here, we analyzed the in vitro
      antiproliferative and ultrastructural effects on T. vaginalis of BPQ-OH, a
      hydroxiquinuclidine derivative that inhibits squalene synthase and is active
      against several protozoa and fungi. We also compared the effects of BPQ-OH on T.
      vaginalis and mammalian cells with those of MTZ. We found that BPQ-OH inhibits in
      vitro proliferation of T. vaginalis, with an IC50 of 46 MUM after 24 h. Although
      this IC50 is 16 times higher than that of MTZ (1.8 MUM), BPQ-OH is less toxic for
      human cell lines than MTZ, with LC50 values of 2,300 and 70 MUM, and selective
      indexes of 50 and 39, respectively. Ultrastructural analyses demonstrated that
      BPQ-OH induced alterations in T. vaginalis, such as rounded and wrinkled cells,
      membrane blebbing and intense vacuolization, leading to cell death, whereas MTZ
      also caused significant changes, including a decrease in hydrogenosomes size and
      endoflagellar forms. Our observations identify BPQ-OH as a promising leading
      compound for the development of novel anti-T. vaginalis drugs and highlight the
      need for further testing this molecule using experimentally infected animals. 

PMID- 24752369
TI  - Myxidium ceccarellii n. sp. (Myxosporea) from the gallbladder of Leporinus
      elongatus (Anastomidae) from the Sao Francisco River, Brazil.
AB  - During a survey of myxozoan parasites of freshwater fish from the Sao Francisco
      River in Minas Gerais State, Brazil, plasmodia of Myxidium ceccarellii n. sp.
      were found in gallbladders of two out of six specimens (22%) of Leporinus
      elongatus (Anastomidae). Parasite plasmodia were translucent and greenish, with
      disporic sporoblasts that develop asynchronously. Mature myxospores were
      ellipsoidal in frontal and lateral views, with slightly pointed ends. The
      surfaces of each valve had four to six longitudinal grooves. Spores dimensions
      were as follows: length 17.7 +/- 0.5 MUm (17.1-18.1), width 10.4 +/- 0.47 MUm
      (9.8-11.3), and thickness 10.1 +/- 0.27 MUm (9.6-10.4). Two polar capsules, one
      at either end of the spore, had the length of 6.3 +/- 0.5 MUm (5.7-7.0) and width
      of 6.4 +/- 0.44 MUm (5.7-6.9), with four to five polar filament turns. Some
      aberrant spores had one or three polar capsules. Partial sequencing of M.
      ceccarellii n. sp. small subunit ribosomal RNA (ssrRNA) gene resulted in 1,845
      bp. This is the first molecular study of a Myxidium species that parasitizes a
      South American freshwater fish. Phylogenetic reconstruction using ssrRNA gene
      sequences showed that M. ceccarellii n. sp. was positioned basally in a
      recognized clade of myxozoans that infect the biliary systems of nonfish
      vertebrates.

PMID- 24752370
TI  - Pulmonary vasculature and critical asthma syndromes: a comprehensive review.
AB  - One of the important factors and consequences in persistent asthma is the change
      in the vasculature of the airways and lung parenchyma. These changes could
      contribute to worsening asthma control and predispose asthmatics to critical
      asthma syndromes. For many years, the contribution of vasculature to severe
      asthma was limited to discussion of small and medium vessel vasculitis commonly
      referred to as Churg-Strauss syndrome. This comprehensive review will explore the
      known mechanisms that are associated with remodeling of the vasculature in a
      variety of critical asthma presentations. Inflammation of pulmonary and bronchial
      small blood vessels may contribute significantly but silently to asthma
      pathobiology. Inflammation in the vasculature of the lung parenchyma can decrease
      lung capacity while inflammation in airway vasculature can decrease airflow. This
      review will provide a modern perspective on Churg-Strauss syndromes with a focus
      on phenotyping, mechanism, and ultimately modern therapeutic approaches. Vascular
      remodeling and airway remodeling are not mutually exclusive concepts in
      understanding the progression of asthma and frequency of acute exacerbations.
      Furthermore, the contribution of vascular leak, particularly in the parenchymal
      vasculature, has become an increasingly recognized component of certain
      presentations of poorly controlled, severe persistent asthmatic and during
      exacerbations. We highlight how these mechanisms can contribute to some the
      severe presentations of influenza infection in patients with a history of asthma.
      The ultimate aim of this review is to summarize the current literature concerning
      vasculitis and the contribution of airway and parenchymal vascular remodeling to
      presentation of persistent asthma and its consequences during acute exacerbations
      and critical asthma syndromes.

PMID- 24752372
TI  - Selecting desirable micronutrient fortificants for plant-based complementary
      foods for infants and young children in low-income countries.
AB  - The World Health Organization (WHO) recommends that both breast-fed and non
      breast-fed children are fed micronutrient fortified complementary foods designed
      to meet their high nutrient requirements from aged 6 to 23 months of age. This
      paper summarises the steps recommended by WHO/FAO to identify the country
      specific micronutrient shortfalls in complementary diets and establish desirable
      levels of bioavailable fortificants for centrally processed plant-based
      complementary foods for infant and young child feeding. The goal of the WHO/FAO
      guidelines is to achieve a desirably low prevalence of inadequate micronutrient
      intakes in the target group whilst simultaneously ensuring minimal risk of
      excessive intakes.

PMID- 24752373
TI  - Central projections of intrinsically photosensitive retinal ganglion cells in the
      macaque monkey.
AB  - Circadian rhythms generated by the suprachiasmatic nucleus (SCN) are entrained to
      the environmental light/dark cycle via intrinsically photosensitive retinal
      ganglion cells (ipRGCs) expressing the photopigment melanopsin and the
      neuropeptide pituitary adenylate cyclase-activating polypeptide (PACAP). The
      ipRGCs regulate other nonimage-forming visual functions such as the pupillary
      light reflex, masking behavior, and light-induced melatonin suppression. To
      evaluate whether PACAP-immunoreactive retinal projections are useful as a marker
      for central projection of ipRGCs in the monkey brain, we characterized the
      occurrence of PACAP in melanopsin-expressing ipRGCs and in the retinal target
      areas in the brain visualized by the anterograde tracer cholera toxin subunit B
      (CtB) in combination with PACAP staining. In the retina, PACAP and melanopsin
      were found to be costored in 99% of melanopsin-expressing cells characterized as
      inner and outer stratifying melanopsin RGCs. Two macaque monkeys were
      anesthetized and received a unilateral intravitreal injection of CtB. Bilateral
      retinal projections containing colocalized CtB and PACAP immunostaining were
      identified in the SCN, the lateral geniculate complex including the pregeniculate
      nucleus, the pretectal olivary nucleus, the nucleus of the optic tract, the
      brachium of the superior colliculus, and the superior colliculus. In conclusion,
      PACAP-immunoreactive projections with colocalized CtB represent retinal
      projections of ipRGCs in the macaque monkey, supporting previous retrograde
      tracer studies demonstrating that melanopsin-containing retinal projections reach
      areas in the primate brain involved in both image- and nonimage-forming visual
      processing.

PMID- 24752374
TI  - Biotin-conjugated N-methylisatoic anhydride: a chemical tool for nucleic acid
      separation by selective 2'-hydroxyl acylation of RNA.
AB  - An isatoic anhydride derivative conjugated to a biotin and a disulfide linker was
      specifically designed for the separation of nucleic acids. Starting from a DNA
      RNA mixture, a selective 2'-hydroxyl acylation of RNAs followed by capture with
      streptavidin-coated magnetic beads and cleavage of the disulfide led to elution
      of RNAs. 

PMID- 24752375
TI  - A silver(I) coordinated phenanthroline-based polymer with high ethylene/ethane
      adsorption selectivity.
AB  - We report a non-porous silver(i) coordinated phenanthroline-based polymer, which
      exhibits a high ideal ethylene/ethane adsorption selectivity (15/1) and high
      ethylene uptake (5.0 mmol g(-1)) at ambient temperature and pressure. Both
      silver(i) coordination and polymer structures are important for the high uptake
      of ethylene. 

PMID- 24752376
TI  - MoS2 nanoflower-decorated reduced graphene oxide paper for high-performance
      hydrogen evolution reaction.
AB  - A facile, one-pot solvothermal method is developed to synthesize MoS2 nanoflowers
      (MoS2NFs) coated on reduced graphene oxide (rGO) paper. The resulting MoS2NF/rGO
      paper serves as a freestanding, flexible and durable working electrode for
      hydrogen evolution reaction (HER), exhibiting an overpotential lowered to -0.19 V
      with a Tafel slope of ~95 mV per decade. 

PMID- 24752371
TI  - Molecular mechanisms in autoimmune type 1 diabetes: a critical review.
AB  - Autoimmune type 1 diabetes is characterized by selective destruction of insulin
      secreting beta cells in the pancreas of genetically susceptible individuals. The
      mechanisms underlying the development of type 1 diabetes are not fully
      understood. However, a widely accepted point is that type 1 diabetes is caused by
      a combination of genetic and environmental factors. Although most type 1 diabetes
      patients do not have a family history, genetic susceptibility does play a vital
      role in beta cell autoimmunity and destruction. Human leukocyte antigen (HLA)
      regions are the strongest genetic determinants, which can contribute 40-50 % of
      the genetic risk to type 1 diabetes. Other genes, including INS also contribute
      to disease risk. The mechanisms of the susceptible genes in type 1 diabetes may
      relate to their respective roles in antigen presentation, beta cell autoimmunity,
      immune tolerance, and autoreactive T cell response. Environmental susceptibility
      factors also contribute to the risk of developing type 1 diabetes. From an
      epigenetic standpoint, the pathologic mechanisms involved in the development of
      type 1 diabetes may include DNA methylation, histone modification, microRNA, and
      molecular mimicry. These mechanisms may act through regulating of gene
      expression, thereby affecting the immune system response toward islet beta cells.
      One of the characteristics of type 1 diabetes is the recognition of islet
      autoantigens by autoreactive CD4(+) and CD8(+) T cells and autoantibodies.
      Autoantibodies against islet autoantigens are involved in autoantigen processing
      and presentation by HLA molecules. This review will mainly focus on the molecular
      mechanism by which genetic, epigenetic, and environmental factors contribute to
      the risk of type 1 diabetes.

PMID- 24752377
TI  - The influence of increased body fat or lean body mass on aerobic performance.
AB  - PURPOSE: The purpose of this study was to determine aerobic performance in men
      with an increased body mass due to (a) high body fat (>21.5%) but with a average
      (59.0-64.3 kg) lean body mass (HBF group) and (b) high lean body mass (>66.3 kg),
      but with average body fat (14.0-18.5%) (HLBM group). METHODS: The men in the HBF
      and HLBM had similar absolute body mass and body mass index (BMI). The aerobic
      performance was also determined in control group. Methods: Study participants
      comprised 39 men aged 21.3 +/- 1.9 years who did not participate in competitive
      sports but were recreationally physically active. Participants were divided into
      three groups. Each group comprised 13 persons. The study involved anthropometric
      measurements, assessing aerobic performance (VO2max) using an incremental test on
      a mechanical treadmill. VO2max was expressed in absolute values, relative to body
      mass (VO2max ? BM(-1)), relative to lean body mass (VO2max ? LBM(-1)), and
      relative to BM raised by the exponents of 0.75 and 0.67. Body composition was
      measured using bioelectrical impedance analysis. RESULTS: No statistically
      significant differences in relative values of VO2max were found between the HBF
      and HLBM groups, in VO2max ? BM(-1) (50.24 +/- 4.56 vs. 53.11 +/- 5.45 mL ? kg(
      1)), VO2max ? LBM(-1) (65.33 +/- 5.63 vs. 63.86 +/- 7.13 mL ? kgLBM(-1)), and
      VO2max ? BM(-0.75) (150.29 +/- 13.5 vs. 160.39 +/- 16.15 mL ? kg(-0.75)). Values
      of VO2max ? BM(-1) were significantly lower in the HBF and HLBM groups than in
      the control group (58.23 +/- 5.84 mL ? kg(-1)). CONCLUSION: High body mass,
      regardless of the cause decreases VO2max ? BM(-1).

PMID- 24752378
TI  - Increased dynamin-1 and -2 protein expression in the aged gerbil hippocampus.
AB  - Dynamin (DNM) plays roles in membrane dynamics, vesicle formation, and transport.
      In the present study, we compared DNM-1 and DNM-2 protein expressions between the
      adult (postnatal month 6) and aged (postnatal month 24) gerbil hippocampus using
      immunohistochemistry and western blot analysis. DNM-1 and DNM-2
      immunoreactivities were primarily observed in hippocampal principal neurons:
      pyramidal cells in the hippocampus proper (CA1-CA3) and granule cells in the
      dentate gyrus. DNM-1 and DNM-2 immunoreactivities in principal neurons were
      significantly increased in the aged group compared with the adult group. In
      addition, DNM-1 and DNM-2 protein levels as well as phospho-DNM-1 level were
      significantly increased in the aged group. These results indicate that the
      increases of DNM-1 and DNM-2 protein expressions may reflect the age-related
      changes in hippocampal function.

PMID- 24752379
TI  - Educating about biomedical research ethics.
AB  - This article examines the global and worsening problem of research misconduct as
      it relates to bio-medico-legal education. While research misconduct has serious
      legal implications, few adequate legal remedies exist to deal with it. With
      respect to teaching, research ethics education should be mandatory for biomedical
      students and physicians. Although teaching alone will not prevent misconduct, it
      promotes integrity, accountability, and responsibility in research. Policies and
      law enforcement should send a clear message that researchers should adhere to the
      highest standards of ethics in research. It is vital that researchers and
      physicians understand basic aspects of law and the legal system in order to
      develop understanding of the medico-legal issues not just in the legal context,
      but with a sound grounding in ethics, social and theoretical contexts so that
      they can practice good medicine. Routine and holistic research ethics education
      across the curriculum for medical students and resident physicians, and
      continuing medical education for practicing doctors, are probably the best ways
      to accomplish this goal.

PMID- 24752380
TI  - Video-rate optical flow corrected intraoperative functional fluorescence imaging.
AB  - Intraoperative fluorescence molecular imaging based on targeted fluorescence
      agents is an emerging approach to improve surgical and endoscopic imaging and
      guidance. Short exposure times per frame and implementation at video rates are
      necessary to provide continuous feedback to the physician and avoid motion
      artifacts. However, fast imaging implementations also limit the sensitivity of
      fluorescence detection. To improve on detection sensitivity in video rate
      fluorescence imaging, we considered herein an optical flow technique applied to
      texture-rich color images. This allows the effective accumulation of fluorescence
      signals over longer, virtual exposure times. The proposed correction scheme is
      shown to improve signal-to-noise ratios both in phantom experiments and in vivo
      tissue imaging.

PMID- 24752381
TI  - Full anterior segment biometry with extended imaging range spectral domain
      optical coherence tomography at 1340 nm.
AB  - We demonstrate an extended-imaging-range anterior-segment optical coherence
      tomography (eAS-OCT) system for the biometric assessment of full AS in human eye.
      This newly developed eAS-OCT operating at 1340-nm wavelength band is
      simultaneously capable of an imaging speed of 120 kHz A-line scan rate, an axial
      resolution of 7.2 MUm, and an extended imaging range of up to 16 mm in air.
      Imaging results from three healthy subjects and one subject with a narrow-angle
      demonstrate the instrument's utility. With this system, it can provide anatomical
      dimensions of AS, including central corneal thickness, anterior chamber width,
      anterior chamber depth, crystalline lens vault, crystalline lens thickness, angle
      opening distance (AOD500/AOD750), and the area described by the trabecular-iris
      space (TISA500/TISA750) at 500/750  MUm. We also use eAS-OCT to image and
      quantify dynamic functional changes of the AS in response to a light stimulus
      that induces physiological pupillary changes as well as accommodative efforts
      that induce lens changes. The results show that the described eAS-OCT is able to
      provide full anatomical biometry for AS and is useful for the studies where the
      dynamic response of AS compartment to certain stimulus is required.

PMID- 24752382
TI  - Possibilities of optical imaging of the (99m)Tc-based radiopharmaceuticals.
AB  - In vivo optical imaging is widely used in preclinical studies. Recently, the
      application of optical imaging systems for preclinical visualization of gamma
      emitting isotopes has become of interest since the evaluation of various organs
      relies on (99m)Tc-based radiopharmaceuticals (RPs). In vitro radioluminescence of
      (99m)Tc-based RPs, including pertechnetate, albumin macroaggregates,
      dimercaptosuccinic acid, phytate colloid, and ethylenediamine tetramethylene
      phosphonic acid, was studied with IVIS Spectrum CTTM optical imaging system. The
      distribution of phytate colloid was also studied in vivo with and without
      scintillating materials and the results were compared with those obtained with a
      conventional scintigraphy. The visible light emission appeared to be due to the
      radioluminescence of water and luminophores contained in RPs rather than from
      Cherenkov radiation. Weak air luminescence affected the background. The
      radioluminescence of fluids induced by (99m)Tc-based tracers could be detected
      using charge-coupled device optical imaging systems. The radioluminescence
      intensity and its spectral distribution depend on the surrounding fluid and known
      luminophores present. Thus, in some cases the in vivo optical imaging is possible
      but the use of scintillator, e.g., borosilicate glass or bismuth germanate, is
      preferred.

PMID- 24752383
TI  - Sex differences in clinical characteristics, hospital management practices, and
      in-hospital outcomes in patients hospitalized in a Vietnamese hospital with a
      first acute myocardial infarction.
AB  - BACKGROUND: Cardiovascular disease is one of the leading causes of morbidity and
      mortality in Vietnam. We conducted a pilot study of Hanoi residents hospitalized
      with acute myocardial infarction (AMI) at the Vietnam National Heart Institute in
      Hanoi. The objectives of this observational study were to examine sex differences
      in clinical characteristics, hospital management, in-hospital clinical
      complications, and mortality in patients hospitalized with an initial AMI.
      METHODS: The study population consisted of 302 Hanoi residents hospitalized with
      a first AMI at the largest tertiary care medical center in Hanoi in 2010.
      RESULTS: The average age of study patients was 66 years and one third were women.
      Women were older (70 vs. 64 years) and were more likely than men to have had
      hyperlipidemia previously diagnosed (10% vs. 2%). During hospitalization, women
      were less likely to have undergone percutaneous coronary intervention (PCI)
      compared with men (57% vs. 74%), and women were more likely to have developed
      heart failure compared with men (19% vs. 10%). Women experienced higher in
      hospital case-fatality rates (CFRs) than men (13% vs. 4%) and these differences
      were attenuated after adjustment for age and history of hyperlipidemia (OR: 2.64;
      95% CI: 1.01, 6.89), and receipt of PCI during hospitalization (OR: 2.09; 95% CI:
      0.77, 5.09). CONCLUSIONS: Our pilot data suggest that among patients hospitalized
      with a first AMI in Hanoi, women experienced higher in-hospital CFRs than men.
      Full-scale surveillance of all Hanoi residents hospitalized with AMI at all Hanoi
      medical centers is needed to confirm these findings. More targeted and timely
      educational and treatment approaches for women appear warranted.

PMID- 24752384
TI  - Transferable pseudoclassical electrons for aufbau of atomic ions.
AB  - Generalizing the LEWIS reactive force field from electron pairs to single
      electrons, we present LEWIS* in which explicit valence electrons interact with
      each other and with nuclear cores via pairwise interactions. The valence
      electrons are independently mobile particles, following classical equations of
      motion according to potentials modified from Coulombic as required to capture
      quantum characteristics. As proof of principle, the aufbau of atomic ions is
      described for diverse main group elements from the first three rows of the
      periodic table, using a single potential for interactions between electrons of
      like spin and another for electrons of unlike spin. The electrons of each spin
      are found to distribute themselves in a fashion akin to the major lobes of the
      hybrid atomic orbitals, suggesting a pointillist description of the electron
      density. The broader validity of the LEWIS* force field is illustrated by
      predicting the vibrational frequencies of diatomic and triatomic hydrogen
      species.

PMID- 24752385
TI  - Clinical utility of the Wechsler Adult Intelligence Scale-Fourth Edition after
      traumatic brain injury.
AB  - The performance of 100 patients with traumatic brain injury (TBI) on the Wechsler
      Adult Intelligence Scale-Fourth Edition (WAIS-IV) was compared with that of 100
      demographically matched neurologically healthy controls. Processing Speed was the
      only WAIS-IV factor index that was able to discriminate between persons with
      moderate-severe TBI on the one hand and persons with either less severe TBI or
      neurologically healthy controls on the other hand. The Processing Speed index
      also had acceptable sensitivity and specificity when differentiating between
      patients with TBI who either did or did not have scores in the clinically
      significant range on the Trail Making Test. It is concluded that WAIS-IV
      Processing Speed has acceptable clinical utility in the evaluation of patients
      with moderate-severe TBI but that it should be supplemented with other measures
      to assure sufficient accuracy in the diagnostic process. 

PMID- 24752387
TI  - Reliability and validity of the Online Continuous Performance Test among
      children.
AB  - OBJECTIVE: The study assesses the reliability and validity of a new Online
      Continuous Performance Test (OCPT) for measuring sustained attention, response
      inhibition, and response time consistency among children. METHOD: The study
      sample comprised 73 children (6-13 years), 47 children with attention deficit
      hyperactivity disorder and 24 in the control group. The Diagnostic Interview
      Schedule for Children was administered to participants' parents to confirm group
      allocation. Children completed the OCPT in a laboratory setting, and a week later
      completed the OCPT at home. RESULTS: Split-half correlation coefficients
      reflected high levels of reliability in the laboratory and at home. Significant
      correlations were found between the laboratory- and home-based OCPT scores.
      Significant differences in OCPT performance were found between children with and
      without attention deficit hyperactivity disorder on the OCPT in the two settings.
      CONCLUSIONS: These results support the reliability and validity of the OCPT and
      suggest that it may serve as an effective tool for the assessment of children's
      attention function in naturalistic settings.

PMID- 24752386
TI  - Construct validity of the Memory for Intentions Screening Test (MIST) in healthy
      older adults.
AB  - The Memory for Intentions Screening Test (MIST) is a clinical measure of
      prospective memory. There is emerging support for the sensitivity and ecological
      relevance of the MIST in clinical populations. In the present study, the
      construct validity of the MIST was evaluated in 40 younger (18-30 years), 24
      young-old (60-69 years), and 37 old-old (70+ years) healthy adults. Consistent
      with expectations derived from the prospective memory and aging literature, older
      adults demonstrated lower scores on the MIST's primary scale scores (particularly
      on the time-based scale), but slightly better performance on the seminaturalistic
      24-hour trial. Among the healthy older adults, the MIST showed evidence of both
      convergent (e.g., verbal fluency) and divergent (e.g., visuoperception)
      correlations with standard clinical tests, although the magnitude of those
      correlations were comparable across the time- and event-based scales. Together,
      these results support the discriminant and convergent validity of the MIST as a
      measure of prospective memory in healthy older adults. 

PMID- 24752389
TI  - Template-free fabrication of mesoporous carbons from carbon quantum dots and
      their catalytic application to the selective oxidation of hydrocarbons.
AB  - Mesoporous carbons (pore size 5 nm) were successfully synthesized without
      templates from carbon quantum dots. As catalysts, both mesoporous carbons and Cu
      nanoparticles on mesoporous carbons show superior catalytic activity and
      stability for the selective oxidation of cyclooctene. 

PMID- 24752388
TI  - Translating extranuclear steroid receptor signaling to clinical medicine.
AB  - The existence and function of extranuclear steroid receptors (SR) to rapidly
      modulate signal transduction is now acknowledged as present in cells and organs
      throughout the body. Work over the past 15 years has defined key mechanisms that
      are required for sex steroid receptors to traffic to the plasma membrane, but
      mechanisms of localization in other cell organelles such as mitochondria is still
      unclear. Signaling by membrane-localized SR has now been reported to impact many
      aspects of adult organ functions, while the roles in organ development are under
      investigation. In hormone-responsive cancers, both extranuclear and nuclear sex
      steroid receptors appear to collaborate in the regulation of some key genes that
      promote malignancy. Here, I review what is understood about the impact of
      extranuclear steroid receptor signaling to mitigate or promote disease processes.

PMID- 24752390
TI  - 2-Cyclopropylimino-3-methyl-1,3-thiazoline hydrochloride inhibits microglial
      activation by suppression of nuclear factor-kappa B and mitogen-activated protein
      kinase signaling.
AB  - The activation of microglia is crucially associated with the neurodegeneration
      observed in many neuroinflammatory pathologies, including multiple sclerosis,
      Parkinson's disease, and Alzheimer's disease. Therefore, the inhibition of
      microglial activation may alleviate certain neurodegenerative processes. We
      previously demonstrated the protective actions of a new drug, 2-cyclopropylimino
      3-methyl-1,3-thiazoline hydrochloride (KHG26377), against glutamate-induced
      excitotoxicity and ischemic neuronal damage in in vivo rat brain study. The
      current investigation explored the possible mechanisms underlying the anti
      inflammatory effects of this compound against lipopolysaccharide (LPS)-stimulated
      activation of cultured BV-2 microglial cells. The results showed that KHG26377
      reduced the production of prostaglandin E2 (PGE2), tumor necrosis factor-alpha
      (TNF-alpha), interleukin-1beta (IL-1beta), reactive oxygen species (ROS), and
      nitric oxide (NO) in LPS-activated microglia. Furthermore, KHG26377 attenuated
      LPS-mediated increases in the protein expression levels of cyclooxygenase-2 (COX
      2), inducible nitric oxide synthase (iNOS), toll-like receptor 4 (TLR4),
      phosphorylated extracellular signal-regulated kinase (p-ERK), and phosphorylated
      p38 mitogen-activated protein kinase (p-p38 MAPK). The compound also prevented
      the LPS-provoked translocation of the nuclear factor-kappa B (NF-kappaB) p65
      subunit (NF-kappaB-p65) from the cytosol into the nucleus of BV-2 cells. These
      findings suggest that KHG26377 may find utility as a therapeutic agent that can
      be further developed for the management of various neuroinflammatory conditions. 

PMID- 24752391
TI  - Depression in silent lacunar infarction: a cross-sectional study of its
      association with location of silent lacunar infarction and vascular risk factors.
AB  - Most previous studies reported a close link between fresh infarcts and post
      stroke depression. However, studies on the relation of depression and silent
      lacunar infarction (SLI) are limited. This study aims to analyze the effects of
      SLI and the vascular risk factors on depression. A total of 243 patients with SLI
      were divided into depression and non-depression groups. The presence and location
      of SLI were evaluated with magnetic resonance imaging. Depression was assessed
      with the Patient Health Questionnaire-9 and vascular risks factors were
      collected. We used t tests and chi (2) test to compare the baseline
      characteristics of the two groups and the multivariate logistic regression model
      to identify the risk factors for depression. Univariate analysis results showed
      that the proportion of patients with SLI in basal ganglia was significantly
      higher in the depression group (65.0 versus 32.8 %; P < 0.001) than in the non
      depression group, and multiple prevalent factors had significant differences
      between the two groups. However, on multivariate logistic analysis, some of these
      factors were eliminated, and SLI in basal ganglia remained an independent
      predictor of depression with an odds ratio of 3.128 (P = 0.018). In addition,
      vascular risk factors, including high body mass index level, presence of
      inflammation markers (e.g., CRP, TNF-alpha, Hs-CRP, and IL-6), and lack of
      physical activity, were associated with depression. Our findings suggest that SLI
      in basal ganglia is associated with a higher risk of depression. Vascular risk
      factors, which are intertwined, may propose the pathological basis of depression
      in SLI.

PMID- 24752392
TI  - Prolonged depersonalization/derealization-like symptom after migraine headache: a
      case report.

PMID- 24752393
TI  - Prevalence and impact of hyperandrogenemia in 1,218 women with polycystic ovary
      syndrome.
AB  - Hyperandrogenemia modifies phenotypic characteristics of women with polycystic
      ovary syndrome (PCOS). The aim of the present study is to evaluate (a) the
      prevalence of hyperandrogenemia in PCOS women (Rotterdam criteria) and (b) the
      impact of either the degree or the type of hyperandrogenemia on phenotype.
      Anthropometric, clinical, hormonal, metabolic and ultrasound characteristics of
      1,218 women with PCOS were analyzed in this cross-sectional study. The prevalence
      of hyperandrogenemia was 58.8 %. Women with hyperandrogenemia had higher
      luteinizing hormone (LH), follicle-stimulating hormone (FSH), free androgen
      index, lower sex-hormone-binding globulin (SHBG) and fasting glucose levels
      compared to women with normal androgens (p < 0.001 for all comparisons; p = 0.001
      for fasting glucose). Regarding the presence of isolated hyperandrogenemia, the
      group with only elevated testosterone levels was termed GT and an analogous
      categorization was made for dehydroepiandrosterone sulfate (GD) and
      androstenedione (Delta4) (GDelta4), respectively. GT, GD and GDelta4 comprised
      the 17.2, 7.6 and 4.1 % of total cohort, respectively. These groups differed
      significantly between them in LH, LH/FSH ratio, and SHBG (p < 0.001).
      Hyperandrogenemia is found in almost 60 % of women with PCOS (Rotterdam
      criteria), and it affects hormonal characteristics of these women such as LH and
      SHBG values. Regarding the impact of isolated hyperandrogenemia on PCOS
      characteristics, it appears that Delta4 and testosterone elevations are
      associated with increased LH levels.

PMID- 24752394
TI  - Effects of genistein on stereological and hormonal characteristics of the
      pituitary somatotrophs in rats.
AB  - The hypothalamic-pituitary somatotropic system plays a pivotal role in the
      regulation of physiological processes and metabolism, which is modulated by
      gonadal steroids. Considering that genistein belongs to the phytoestrogen family
      and acts via similar mechanisms to estrogens, the present study was designed to
      demonstrate whether genistein modulates the morphofunctional characteristic of
      somatotrophs [growth hormone (GH) cells] in adult rats in comparison with the
      effects of estradiol. In the study, the orchidectomized adult rats were used as
      an appropriate model system for testing the effects of this hormone-like
      substance. Changes in the pituitary somatotrophs were evaluated histologically
      and stereologically, while GH level was determined biochemically. Using
      immunolabelling and stereological methods, we showed that orchidectomy (Orx)
      provoked the decrease of GH cell volume density. After estradiol treatment of Orx
      rats, the most prominent change concerned the pituitary relative intensity of GH
      fluorescence and circulating GH level, which were elevated 77 % and 4.7-fold,
      respectively. Clearly, in contrast to orchidectomy, estradiol treatment enhanced
      the GH cells activity. Genistein treatment increased pituitary weight and volume,
      GH cell volume density, the total number of GH cells, and GH blood concentration
      (1.3-fold) in comparison to the Orx group. Although identical tendencies followed
      estradiol and genistein administration, the changes observed after genistein
      treatment were milder compared to estradiol treatment.

PMID- 24752395
TI  - The use of a rigid tritopic phosphonic ligand for the synthesis of a robust
      honeycomb-like layered zirconium phosphonate framework.
AB  - 1,3,5-Tris(4-phosphonophenyl)benzene was synthesized via a microwave heating
      assisted route and was subsequently used for the preparation of a new zirconium
      phosphonate with honeycomb-like structure displaying remarkable thermal stability
      and hydrolysis resistance. 

PMID- 24752396
TI  - Three-dimensional study of nasopalatine canal morphology: a descriptive
      retrospective analysis using cone-beam computed tomography.
AB  - PURPOSE: For dental implant treatment planning and placement, a precise anatomic
      description of the nasopalatine canal (NC) is necessary. This descriptive
      retrospective study evaluated dimensions of the NC and buccal bone plate (BBP)
      and the tridimensional association of the anatomic variants of NC, using cone
      beam computed tomography (CBCT). METHODS: This study included 230 CBCTs. Sagittal
      slices were used for measurements of the NC and BBP and to evaluate shape and
      direction-course of the NC. Coronal slices were used to assess NC shape and axial
      slices to assess number of incisive foramina and foramina of Stenson. RESULTS:
      Mean NC length was 12.34 +/- 2.79 mm, statistically significant differences were
      detected between genders (p < 0.001). Mean BBP length was 20.87 +/- 3.68 mm,
      statistically significant differences were found for the dental status (p <
      0.001) and mean BBP width was 6.83 +/- 1.28 mm, significant differences were
      detected between genders (p < 0.001). Mean nasopalatine angle was 73.33 degrees 
      +/- 8.11 degrees , significant differences were found in sagittal and coronal
      classifications. The most prevalent canal was: cylindrical sagittal shape (48.2
      %); slanted-straight direction-course (57.6 %); Ya-type coronal shape (42.4 %);
      and one foramen incisive with two Stenson's foramina (1-2) (50.9 %). Sagittal
      shape was associated with sagittal direction-course (p < 0.001). Coronal shape
      was associated with axial classification (p < 0.001). CONCLUSIONS: The NC anatomy
      is highly variable. Gender is related to the NC length and BBP width, while
      dental status is related to BBP length. There was an association between the
      different sagittal classifications of the NC and between the coronal shape and
      axial classification.

PMID- 24752397
TI  - Prevalence of bifid mandibular canals in panoramic radiographs: a maxillofacial
      surgical scope.
AB  - PURPOSE: The present study aims to estimate the prevalence of bifid mandibular
      canals in patients treated at the Dental Clinic of the Federal University of
      Parana, Brazil. METHODS: The sample consisted of 3,024 panoramic radiographs from
      male (n = 1,155) and female (n = 1,869) patients (mean age 30 years). An
      experienced radiologist analyzed the panoramic radiographs according to the study
      of Langlais et al. (J Am Dental Assoc 110:923-926, 1985), which classifies bifid
      mandibular canals into four different types. RESULTS: Sixty patients (1.98 %)
      presented bifid mandibular canals. Specifically, 50 patients revealed bifid
      mandibular canals type I, while 10 patients revealed bifid mandibular canals type
      II. All the variations were unilateral. In addition, statistically significant
      results were not observed for gender distribution. CONCLUSION: The present
      findings indicate a low prevalence of morphologic alterations of the mandibular
      canal in the studied population. However, the present outcome highlights the
      clinical relevance of investigating the radiologic morphology of the mandibular
      canal prior to surgical interventions.

PMID- 24752401
TI  - Ultrafast and scalable laser liquid synthesis of tin oxide nanotubes and its
      application in lithium ion batteries.
AB  - Laser-induced photo-chemical synthesis of SnO2 nanotubes has been demonstrated by
      employing a nanoporous polycarbonate membrane as a template. The SnO2 nanotube
      diameter can be controlled by the nanoporous template while the nanotube length
      can be tuned by laser parameters and reaction duration. The microstructure
      characterization of the nanotubes indicates that they consist of mesoporous
      structures with sub 5 nm size nanocrystals connected by the twinning structure.
      The application of SnO2 nanotubes as an anode material in lithium ion batteries
      has also been explored, and they exhibited high capacity and excellent cyclic
      stability. The laser based emerging technique for scalable production of
      crystalline metal oxide nanotubes in a matter of seconds is remarkable. The
      compliance of the laser based technique with the existing technologies would lead
      to mass production of novel nanomaterials that would be suitable for several
      emerging applications. 

PMID- 24752399
TI  - The role of Mss11 in Candida albicans biofilm formation.
AB  - Candida albicans is an opportunistic human pathogen that can form a biofilm on
      biotic or inert surfaces such as epithelia and clinical devices. In this study,
      we examine the formation of C. albicans biofilm by establishing a key gene
      centered network based on protein-protein interaction (PPI) and gene expression
      datasets. Starting from C. albicans Cph1 and Efg1, transcription factors
      associated with morphogenesis of biofilm formation, a network elucidates the
      complex cellular process and predicts potential unknown components related to
      biofilm formation. Subsequently, we analyzed the functions of Mss11 among these
      identified proteins to test the efficiency of the proposed computational
      approach. MSS11-deleted mutants were compared with a wild-type strain, indicating
      that the mutant is defective in forming a mature biofilm and partially attenuates
      the virulence of C. albicans in an infected mouse model. Finally, a DNA
      microarray analysis was conducted to identify the potential target genes of C.
      albicans Mss11. The findings of this study clarify complex gene or protein
      interaction during the biofilm formation process of C. albicans, supporting the
      application of a systems biology approach to study fungal pathogenesis. 

PMID- 24752400
TI  - Negative regulation of MAP kinase signaling in Drosophila by Ptp61F/PTP1B.
AB  - PTP1B is an important negative regulator of insulin and other signaling pathways
      in mammals. However, the role of PTP1B in the regulation of RAS-MAPK signaling
      remains open to deliberation, due to conflicting evidence from different
      experimental systems. The Drosophila orthologue of mammalian PTP1B, PTP61F, has
      until recently remained largely uncharacterized. To establish the potential role
      of PTP61F in the regulation of signaling pathways in Drosophila and particularly
      to help resolve its fundamental function in RAS-MAPK signaling, we generated a
      new allele of Ptp61F as well as employed both RNA interference and overexpression
      alleles. Our results validate recent data showing that the activity of insulin
      and Abl kinase signaling is increased in Ptp61F mutants and RNA interference
      lines. Importantly, we establish negative regulation of the RAS/MAPK pathway by
      Ptp61F activity in whole animals. Of particular interest, our results document
      the modulation of hyperactive MAP kinase activity by Ptp61F alleles, showing that
      the phosphatase intervenes to directly or indirectly regulate MAP kinase itself. 

PMID- 24752403
TI  - Kangaroo mother care to reduce morbidity and mortality in low birthweight
      infants.
AB  - BACKGROUND: Kangaroo mother care (KMC), originally defined as skin-to-skin
      contact between a mother and her newborn, frequent and exclusive or nearly
      exclusive breastfeeding, and early discharge from hospital, has been proposed as
      an alternative to conventional neonatal care for low birthweight (LBW) infants.
      OBJECTIVES: To determine whether there is evidence to support the use of KMC in
      LBW infants as an alternative to conventional neonatal care. SEARCH METHODS: The
      standard search strategy of the Cochrane Neonatal Group was used. This included
      searches in MEDLINE, EMBASE, LILACS, POPLINE, CINAHL databases (all from
      inception to March 31, 2014) and the Cochrane Central Register of Controlled
      Trials (The Cochrane Library, Issue 3, 2014) In addition, we searched the web
      page of the Kangaroo Foundation, conference and symposia proceedings on KMC, and
      Google scholar. SELECTION CRITERIA: Randomized controlled trials comparing KMC
      versus conventional neonatal care, or early onset KMC (starting within 24 hours
      after birth) versus late onset KMC (starting after 24 hours after birth) in LBW
      infants. DATA COLLECTION AND ANALYSIS: Data collection and analysis were
      performed according to the methods of the Cochrane Neonatal Review Group. MAIN
      RESULTS: Eighteen studies, including 2751 infants, fulfilled inclusion criteria.
      Sixteen studies evaluated KMC in LBW infants after stabilization, one evaluated
      KMC in LBW infants before stabilization, and one compared early onset KMC with
      late onset KMC in relatively stable LBW infants. Thirteen studies evaluated
      intermittent KMC and five evaluated continuous KMC. At discharge or 40-41 weeks'
      postmenstrual age, KMC was associated with a reduction in the risk of mortality
      (typical risk ratio (RR) 0.60, 95% confidence interval (CI) 0.39 to 0.92; eight
      trials, 1736 infants), nosocomial infection/sepsis (typical RR 0.45, 95% CI 0.27
      to 0.76), hypothermia (typical RR 0.34, 95% CI 0.17 to 0.67), and length of
      hospital stay (typical mean difference 2.2 days, 95% CI 0.6 to 3.7). At latest
      follow up, KMC was associated with a decreased risk of mortality (typical RR
      0.67, 95% CI 0.48 to 0.95; 11 trials, 2167 infants) and severe infection/sepsis
      (typical RR 0.56, 95% CI 0.40 to 0.78). Moreover, KMC was found to increase some
      measures of infant growth, breastfeeding, and mother-infant attachment. There
      were no significant differences between KMC infants and controls in
      neurodevelopmental and neurosensory impairment at one year of corrected age.
      Sensitivity analysis suggested that the inclusion of studies with high risk of
      bias did not affect the general direction of findings or the size of the
      treatment effect for the main outcomes. AUTHORS' CONCLUSIONS: The evidence from
      this updated review supports the use of KMC in LBW infants as an alternative to
      conventional neonatal care mainly in resource-limited settings. Further
      information is required concerning effectiveness and safety of early onset
      continuous KMC in unstabilized or relatively stabilized LBW infants, long term
      neurodevelopmental outcomes, and costs of care.

PMID- 24752402
TI  - Clinical presentation and disease course of inflammatory bowel disease differs by
      race in a large tertiary care hospital.
AB  - BACKGROUND: While the incidence of inflammatory bowel disease (IBD) among African
      Americans (AAs) is increasing, there is limited understanding of phenotypic
      differences and outcomes by race. AIM: To describe disease characteristics of AA
      patients compared to Caucasian (Ca) patients in a tertiary care population.
      METHODS: We performed a cross-sectional review of the IBD registry at the
      University of Chicago from January 2008 to January 2013. Data regarding race,
      phenotype, disease onset, disease duration, medical therapy, and surgical
      treatment were abstracted from the database, then compared via Pearson's chi
      square analysis, Kruskal-Wallis analysis, and logistic regression with a
      significance level of p < 0.05. RESULTS: A total of 1,235 patients with Crohn's
      disease (CD) and 541 patients with ulcerative colitis (UC) included 108 AA CD
      patients and 28 AA UC patients. AA CD patients had an increased rate of IBD
      related arthralgias (36.5 vs. 23.9 %, p < 0.01) and surgery (p < 0.01), less
      ileal involvement (57.8 vs. 71.0 %, p < 0.01), and no differences for other
      extraintestinal manifestations or disease locations compared to Ca CD patients.
      AA UC patients were older at diagnosis, had an increased rate of arthralgias
      (28.6 vs. 14.6 %, p = 0.047) and ankylosing spondylitis/sacroiliitis (7.1 vs. 1.6
      %, p = 0.035), with no differences for disease extent or rate of IBD-related
      surgeries compared to Ca UC patients. There were no differences in medication
      usage by race for CD and UC patients. CONCLUSION: We identified significant
      differences in disease characteristics and extraintestinal manifestations between
      AA and Ca IBD patients in a large tertiary care population. These results have
      implications for future genotype-phenotype studies.

PMID- 24752404
TI  - MicroRNA repertoire for functional genome research in tilapia identified by deep
      sequencing.
AB  - The Nile tilapia (Oreochromis niloticus; Cichlidae) is an economically important
      species in aquaculture and occupies a prominent position in the aquaculture
      industry. MicroRNAs (miRNAs) are a class of noncoding RNAs that post
      transcriptionally regulate gene expression involved in diverse biological and
      metabolic processes. To increase the repertoire of miRNAs characterized in
      tilapia, we used the Illumina/Solexa sequencing technology to sequence a small
      RNA library using pooled RNA sample isolated from the different developmental
      stages of tilapia. Bioinformatic analyses suggest that 197 conserved and 27 novel
      miRNAs are expressed in tilapia. Sequence alignments indicate that all tested
      miRNAs and miRNAs* are highly conserved across many species. In addition, we
      characterized the tissue expression patterns of five miRNAs using real-time
      quantitative PCR. We found that miR-1/206, miR-7/9, and miR-122 is abundantly
      expressed in muscle, brain, and liver, respectively, implying a potential role in
      the regulation of tissue differentiation or the maintenance of tissue identity.
      Overall, our results expand the number of tilapia miRNAs, and the discovery of
      miRNAs in tilapia genome contributes to a better understanding the role of miRNAs
      in regulating diverse biological processes. 

PMID- 24752405
TI  - Comparative modeling and virtual screening for the identification of novel
      inhibitors for myo-inositol-1-phosphate synthase.
AB  - Myo-inositol-1-phosphate (MIP) synthase is a key enzyme in the myo-inositol
      biosynthesis pathway. Disruption of the inositol signaling pathway is associated
      with bipolar disorders. Previous work suggested that MIP synthase could be an
      attractive target for the development of anti-bipolar drugs. Inhibition of this
      enzyme could possibly help in reducing the risk of a disease in patients. With
      this objective, three dimensional structure of the protein was modeled followed
      by the active site prediction. For the first time, computational studies were
      carried out to obtain structural insights into the interactive behavior of this
      enzyme with ligands. Virtual screening was carried out using FILTER, ROCS and EON
      modules of the OpenEye scientific software. Natural products from the ZINC
      database were used for the screening process. Resulting compounds were docked
      into active site of the target protein using FRED (Fast Rigid Exhaustive Docking)
      and GOLD (Genetic Optimization for Ligand Docking) docking programs. The analysis
      indicated extensive hydrogen bonding network and hydrophobic interactions which
      play a significant role in ligand binding. Four compounds are shortlisted and
      their binding assay analysis is underway. 

PMID- 24752407
TI  - Hec1 inhibition alters spindle morphology and chromosome alignment in porcine
      oocytes.
AB  - Aneuploidy is caused by incorrect chromosome segregation and can result in cancer
      or birth defects. The spindle assembly checkpoint (SAC) guarantees proper cell
      cycle progression. Highly Expressed in Cancer protein 1 (Hec1, also called Ndc80)
      is the core component of the Ndc80 complex and is involved in regulating both
      kinetochore-microtubule interactions and the SAC during mitosis in multiple cell
      types. However, its involvement in pig oocyte meiotic maturation remains
      uncertain. Thus, we investigated Hec1 expression, localization, and possible
      functions during porcine oocyte meiosis. Immunofluorescent staining showed that
      Hec1 was expressed in porcine oocytes and was associated with centromeres at both
      the metaphase I and metaphase II stages. Disrupting Hec1 function with its
      inhibitor INH1 resulted in polar body extrusion defects in porcine oocytes.
      Moreover, inhibiting Hec1 activity also resulted in severe chromosome
      misalignments and aberrant spindle morphology. Our results showed a unique
      localization pattern for Hec1 in porcine oocytes and suggested that Hec1 was
      required for chromosome alignment and spindle organization. Thus, Hec1 might
      regulate spindle checkpoint activity during mammalian oocyte meiosis. 

PMID- 24752406
TI  - Association of the UCP polymorphisms with susceptibility to obesity: case-control
      study and meta-analysis.
AB  - This paper describes a case-control study and a meta-analysis performed to
      evaluate if the following polymorphisms are associated with presence of obesity: 
      3826A/G (UCP1); -866G/A, Ala55Val and Ins/Del (UCP2) and -55C/T (UCP3). The case
      control study enrolled 282 obese and 483 non-obese patients with type 2 diabetes.
      A literature search was made to identify all studies that evaluated associations
      between UCP1-3 polymorphisms and obesity. In the case-control study the
      distributions of the UCP variants did not differ between obese and non-obese
      groups (P > 0.05). Forty-seven studies were eligible for the meta-analysis and
      the results showed that the UCP2 -866G/A and UCP3 -55C/T polymorphisms were
      associated with protection to obesity in Europeans (OR = 0.89, 95% CI 0.82-0.97
      and OR = 0.88, 95% CI 0.80-0.97, respectively). The UCP2 Ala55 val polymorphism
      was associated with obesity in Asians (OR = 1.61, 95% CI 1.13-2.30). The UCP2
      Ins/Del polymorphism was associated with obesity mainly in Europeans (OR = 1.19,
      95% CI 1.00-1.42). There was no significant association of the UCP1 -3826A/G
      polymorphism with obesity. In our case-control study we were not able to
      demonstrate any association between UCP polymorphisms and obesity in T2DM
      patients; however, in the meta-analysis we detected a significant association of
      UCP2 -866G/A, Ins/Del, Ala55Val and UCP3 -55C/T polymorphisms with obesity.

PMID- 24752409
TI  - Electrocatalytic oxygen reduction kinetics on Fe-center of nitrogen-doped
      graphene.
AB  - The Fe/N/C catalysts have emerged recently as a representative class of non-Pt
      catalysts for oxygen electrocatalytic reduction, which could have a competitive
      catalytic performance to Pt. However, the nature of the catalyst remains elusive,
      especially on the active site structure and the electrocatalytic kinetics. Here
      we examine two kinds of Fe/N active sites for Fe/N/C catalysts, namely, the four
      coordinated FeN4 and the five-coordinated Fe(CN)N4 centers embedded in graphene
      layers. By using large-scale first principles calculations with a periodic
      continuum solvation model based on the Modified-Poisson-Boltzmann equation (CM
      MPB), we identified the four (4e) and two electron (2e) oxygen reduction pathways
      under acidic conditions. We find that both 4e and 2e pathways involves the
      formation of an OOH intermediate, which breaks its O-OH bond in the 4e pathway
      but is reduced to H2O2 in the 2e pathway. We show that at 0.8 V vs. SHE, the 4e
      pathway is preferred at both FeN4 and Fe(CN)N4 centers, but the 2e pathway is
      kinetically also likely on the Fe(CN)N4 center. The O-OH bond breaking of OOH is
      the key kinetic step, which has a similar free energy barrier to the OH reduction
      on the FeN4 center, and is the rate-determining step on the Fe(CN)N4 center. Due
      to the high adsorption energy of Fe towards the fifth ligand, such as OH and CN,
      we expect that the active site of the real Fe/N/C catalyst is the five
      coordinated Fe center. We found that the barrier of the O-OH bond breaking step
      is not sensitive to potential and a Tafel slope of 60 mV is predicted for the ORR
      on the Fe(CN)N4 center, which is consistent with experimental observation. 

PMID- 24752408
TI  - Differential soybean gene expression during early phase of infection with
      Mungbean yellow mosaic India virus.
AB  - Mungbean yellow mosaic India virus (MYMIV), a bipartite begomovirus, causes
      yellow mosaic disease to soybean. Studies related to host gene expression in
      response to begomovirus infection have mostly been performed with systemically
      infected tissues at a later period of infection. In this study, soybean gene
      expression analysis has been performed to understand local responses against
      MYMIV at an early stage of infection before appearance of detectable limit of
      late viral transcripts. 444 soybean transcripts belonging to eleven functional
      categories showed significant changes in expression level at two days after
      infection. MYMIV infection resulted in enhanced expression of genes associated
      with hypersensitive response, programmed cell death and resistance response
      pathways and reduced expression of genes for photosynthesis and sugar transport.
      Comparative expression analysis of selected transcripts in the susceptible and a
      resistant variety displayed differential expression of host genes involved in
      intercellular virus movement and long distance signaling of systemic acquired
      resistance. 

PMID- 24752410
TI  - Everolimus in combination with octreotide long-acting repeatable in a first-line
      setting for patients with neuroendocrine tumors: an ITMO group study.
AB  - BACKGROUND: Preclinical and clinical studies suggest synergistic activity between
      somatostatin analogues and mammalian target of rapamycin inhibitors. The activity
      and safety of everolimus was assessed in combination with octreotide long-acting
      repeatable (LAR) in patients with neuroendocrine tumors (NETs) of
      gastroenteropancreatic and lung origin. METHODS: This was a phase 2, multicenter
      trial using a Simon's 2-stage minimax design. Treatment-naive patients with
      advanced well-differentiated NETs of gastroenteropancreatic tract and lung origin
      received everolimus 10 mg daily, in combination with octreotide LAR 30 mg every
      28 days. The primary endpoint was objective response rate (ORR). RESULTS: A total
      of 50 patients (median age, 60.5 years) were enrolled. Primary tumor sites were:
      pancreas (14 patients), lung (11 patients), ileum (9 patients), jejunum and
      duodenum (2 patients), and unknown (14 patients). Thirteen patients (26%) had
      carcinoid syndrome. Treatment-related adverse events (AEs) were mostly grade 1 or
      2; the only grade 4 AE was mucositis in 1 patient, whereas grade 3 AEs included
      skin rash in 1 case (2%), stomatitis in 4 cases (8%), and diarrhea in 11 cases
      (22%). The ORR was 18%; 2% of patients had a complete response (CR), 16% a
      partial response (PR) and 74% achieved stable disease (SD). All CRs and all PRs
      as well as 92% of SDs had a duration >= 6 months. The clinical benefit (CR+PR+SD)
      was 92%. At a median follow-up of 277 days, median time to progression and
      overall survival were not reached. CONCLUSIONS: The everolimus-octreotide LAR
      combination was active and well tolerated in these previously treated patients
      with advanced NETs, suggesting a possible role as first-line treatment in
      patients with NET.

PMID- 24752412
TI  - Valorization of traditional foods: nutritional and bioactive properties of Cicer
      arietinum L. and Lathyrus sativus L. pulses.
AB  - BACKGROUND: The use of traditional foods can enrich our diet, perpetuating
      important elements of local knowledge and cultural inheritance. Raw, soaked and
      cooked samples of two Fabaceae species (Cicer arietinum L. and Lathyrus sativus
      L.) were characterized regarding nutritional and bioactive properties. RESULTS:
      L. sativus gave the highest carbohydrate, protein, ash, saturated fatty acid and
      polyunsaturated fatty acid content, and lowest fat and energy value. Furthermore,
      it also showed the highest concentration of flavonoids and antioxidant activity.
      Cicer arietinum gave the highest concentration of sugars, organic acids and
      tocopherols. The soaking process did not significantly affect macronutrients, but
      cooking (boiling) decreased protein, ash, sugars and organic acids, and increased
      carbohydrates, fat, tocopherols, bioactive compounds and antioxidant activity. No
      differences were obtained for fatty acid composition. CONCLUSION: The present
      study highlights the nutritional profile and bioactive properties of these
      agricultural varieties of C. arietinum and L. sativus pulses, and valorizes their
      traditional consumption and the use in modern diets.

PMID- 24752411
TI  - Genome-wide analysis of host factors in nodavirus RNA replication.
AB  - Flock House virus (FHV), the best studied of the animal nodaviruses, has been
      used as a model for positive-strand RNA virus research. As one approach to
      identify host genes that affect FHV RNA replication, we performed a genome-wide
      analysis using a yeast single gene deletion library and a modified, reporter gene
      expressing FHV derivative. A total of 4,491 yeast deletion mutants were tested
      for their ability to support FHV replication. Candidates for host genes
      modulating FHV replication were selected based on the initial genome-wide
      reporter gene assay and validated in repeated Northern blot assays for their
      ability to support wild type FHV RNA1 replication. Overall, 65 deletion strains
      were confirmed to show significant changes in the replication of both FHV genomic
      RNA1 and sub-genomic RNA3 with a false discovery rate of 5%. Among them, eight
      genes support FHV replication, since their deletion significantly reduced viral
      RNA accumulation, while 57 genes limit FHV replication, since their deletion
      increased FHV RNA accumulation. Of the gene products implicated in affecting FHV
      replication, three are localized to mitochondria, where FHV RNA replication
      occurs, 16 normally reside in the nucleus and may have indirect roles in FHV
      replication, and the remaining 46 are in the cytoplasm, with functions enriched
      in translation, RNA processing and trafficking. 

PMID- 24752413
TI  - Major progress towards elucidating brain wiring diagrams.

PMID- 24752415
TI  - Change of the complexity of coronary artery disease after percutaneous coronary
      intervention with drug-eluting stent.
AB  - We investigated changes of the complexity of coronary artery disease (CAD) after
      drug-eluting stent (DES) implantation using SYNTAX score and the predictor of
      worsened SYNTAX score at follow-up. 116 consecutive patients who underwent de
      novo PCI with first-generation DES were enrolled. SYNTAX scores were obtained
      from coronary angiography before PCI, just after final PCI and at follow-up after
      6-8 months and investigated. SYNTAX score changed from 19.8 +/- 11.9 before PCI
      to 13.7 +/- 10.6 after PCI and to 15.0 +/- 11.7 at follow-up. SYNTAX score before
      PCI was significantly correlated with a difference of SYNTAX score between before
      and after PCI [acute improved score (AIS)] and between after PCI and at follow-up
      (r = 0.5, p < 0.0001, r = 0.3, p = 0.002, respectively). At follow-up, SYNTAX
      score improved from just after PCI in 6.0% of the subjects, did not change in
      60.3% and worsened in 33.6%. In-stent restenosis occurred in 43.8% of the
      patients with worsened score, and progression of lesion occurred in 62.5%. On
      multivariate analysis for worsened score, only diabetes was a significant
      independent predictor (OR 3.0, 95%CI 1.3-7.2, p = 0.01); however, SYNTAX scores
      both before PCI and AIS were not predictors. With regard to re-exacerbation of
      the complexity of CAD after PCI with DES, we need to exhibit caution in diabetic
      patients and there is no need to consider the complexity of CAD before PCI or the
      degree of acute improvement of complexity of CAD with PCI.

PMID- 24752416
TI  - High sensitivity of flow cytometry improves detection of occult leptomeningeal
      disease in acute lymphoblastic leukemia and lymphoblastic lymphoma.
AB  - Conventional cytology (CC) of cerebrospinal fluid (CSF) fails to demonstrate
      malignant cells in up to 45 % of patients with acute lymphoblastic leukemia or
      lymphoblastic lymphoma (ALL/LL) in whom occult leptomeningeal disease is present.
      Flow cytometry (FCM) is considered more sensitive than CC, but clinical
      implications of CC negativity/CC positivity are not yet established. CSF samples
      from 38 adult patients with newly diagnosed ALL/LL were examined. Five (13 %) and
      nine (24 %) specimens were CC positive-FC positive (FCM(pos)/CC(pos)) and CC
      negative-FC positive (CC(neg)/FCM(pos)), respectively. The remaining 24 (63 %)
      samples were double negative (CC(neg)/FCM(neg)) (p = 0.001). CC(neg)/FCM(pos)
      patients showed a significantly shorter overall survival (OS) compared to
      CC(neg)/FCM(neg) ones. In multivariate analysis, the status of single FCM
      positivity was demonstrated to affect independently duration of OS (p = 0.005).
      In conclusion, FCM significantly improves detection of leptomeningeal occult
      localization in ALL/LL and appears to anticipate an adverse outcome. Further
      prospective studies on larger series are needed to confirm this preliminary
      observation. 

PMID- 24752417
TI  - Is it really possible to cure hairy cell leukemia patients only with frontline
      therapy?
AB  - Hairy cell leukemia (HCL) patients could have an excellent prognosis with
      adequate treatment. Treatments are not generally curative but are extremely
      effective in inducing long-lasting clinical remissions. An observational
      retrospective study was conducted on a single-center registry of 144 patients
      with a median follow-up of 11.5 years, focusing on long-lasting continuous first
      complete remissions (CR) wondering if patients can be cured only with front-line
      approach. CR for more than 5 years after first-line therapy were found in 22.2 %
      cases. The median duration of response was 9.8 years, while for relapsed
      patients, the first response had a median duration of 2.4 years. Three different
      subsets of long-lasting first CR were identified: 15 patients are between 5 and
      10 years with a median duration of CR of 6.5 years; 7 patients are between 10 and
      15 years with a median duration of CR of 12.3 years; and 10 patients present a
      follow-up superior to 15 years with a median duration of CR of 20.0 years. There
      is a need for continuous study in this field to better define the optimal
      therapeutic regimen and, in particular, the biological issues since at least 20
      25 % of HCL patients can be cured with only one treatment. 

PMID- 24752418
TI  - Acquired B cell immunophenotype of follicular dendritic cells in a B cell
      depleted lymph node after treatment with rituximab.